PMID- 15140365
TI  - A quantitative analysis of the content and structure of public requests for
      private interaction posted in online public chatrooms.
AB  - Evidence is presented suggesting that the majority (88%) of online requests for
      private computer-mediated communication posted in Internet Relay Chat (IRC)
      chatrooms are derivations of the following prototypical structure: (a) a target
      specifier, e.g., "any girls"; (b) the communication request itself, e.g., "wanna
      chat"; (c) a self-identifier, e.g., "to a guy"; and (d) a communication
      directive, e.g., "msg me!" A methodology capable of identifying individual
      differences in the frequency of language usage on IRC was developed and used to
      generate a taxonomy of the phrases commonly used in each of these four
      components. This taxonomy of 82 phrases accounted for 14.5% of the total language
      used across a variety of IRC chatrooms and 77% of the words used in requests for
      private interaction. It also identified at least one component in 83% of all
      requests for private interaction posted on IRC, while having only a 10% rate of
      false (non-request) identification. The reduced complexity and increased
      explicitness of requests for private interaction on IRC is interpreted using
      politeness theory. The application of the current methodology for research
      assessing the formation of online romantic and interpersonal relationships is
      considered, as are the utility of quantitative analyses of discourse structures
      in computer-mediated communication for profiling people who use IRC for various
      purposes.

PMID- 15140364
TI  - Variations in internet-related problems and psychosocial functioning in online
      sexual activities: implications for social and sexual development of young
      adults.
AB  - This survey of 760 university students examined differences in Internet-related
      problems and psychosocial functioning between four patterns of participation in
      online sexual information and entertainment activities. Students who did not
      participate in either online sexual activity were more satisfied with their
      offline life and more connected to friends and family. Those who engaged in both
      online sexual activities were more dependent on the Internet and reported lower
      offline functioning. Students who only sought sexual information maintained
      strong offline affiliations. Those who only sought entertainment did not report
      lower offline functioning. Respondents most deficient in offline social support
      did not report compensatory online support. Despite students' common
      participation in online sexual activities (OSA) as a venue for social and sexual
      development, those relying on the Internet and the affiliations it provides
      appear at risk of decreased social integration. The authors discussed the
      finding's implications for social and sexual development.

PMID- 15140366
TI  - Enter your e-mail address: how German Internet users manage their e-mail
      addresses.
AB  - Writing E-mail is the most popular Internet activity. Meanwhile, many people have
      more than one E-mail address. The question how people manage their E-mail
      addresses, more specifically, whether they use them deliberately for different
      purposes, is the central question of this paper. E-mail addresses vary in the
      amount of identifying information they convey (e.g., name, gender, status). It is
      proposed that the amount of identifying information an email address contains is
      a predictor of usage for a specific purpose. However, it is assumed that not all
      people choose email addresses in a rational way, according to the optimal fit
      between amount of identifying information and purpose of the E-mail. Thus, the
      role of other factors is tested as well. An online survey on German Internet
      users showed that it is common to have more than one E-mail address. Especially
      free webmail addresses (freemail) are extremely popular. People used more
      anonymous E-mail addresses when they expected spam or were concerned about
      privacy. However, there were also interindividual differences in the management
      of E-mail addresses.

PMID- 15140367
TI  - Linkages between depressive symptomatology and Internet harassment among young
      regular Internet users.
AB  - Recent reports indicate 97% of youth are connected to the Internet. As more young
      people have access to online communication, it is integrally important to
      identify youth who may be more vulnerable to negative experiences. Based upon
      accounts of traditional bullying, youth with depressive symptomatology may be
      especially likely to be the target of Internet harassment. The current
      investigation will examine the cross-sectional relationship between depressive
      symptomatology and Internet harassment, as well as underlying factors that may
      help explain the observed association. Youth between the ages of 10 and 17 (N =
      1,501) participated in a telephone survey about their Internet behaviors and
      experiences. Subjects were required to have used the Internet at least six times
      in the previous 6 months to ensure a minimum level of exposure. The caregiver
      self-identified as most knowledgeable about the young person's Internet behaviors
      was also interviewed. The odds of reporting an Internet harassment experience in
      the previous year were more than three times higher (OR: 3.38, CI: 1.78, 6.45)
      for youth who reported major depressive symptomatology compared to mild/absent
      symptomatology. When female and male respondents were assessed separately, the
      adjusted odds of reporting Internet harassment for males who also reported DSM IV
      symptoms of major depression were more than three times greater (OR: 3.64, CI:
      1.16, 11.39) than for males who indicated mild or no symptoms of depression. No
      significant association was observed among otherwise similar females. Instead,
      the association was largely explained by differences in Internet usage
      characteristics and other psychosocial challenges. Internet harassment is an
      important public mental health issue affecting youth today. Among young, regular
      Internet users, those who report DSM IV-like depressive symptomatology are
      significantly more likely to also report being the target of Internet harassment.
      Future studies should focus on establishing the temporality of events, that is,
      whether young people report depressive symptoms in response to the negative
      Internet experience, or whether symptomatology confers risks for later negative
      online incidents. Based on these cross-sectional results, gender differences in
      the odds of reporting an unwanted Internet experience are suggested, and deserve
      special attention in future studies.

PMID- 15140369
TI  - Impact of genetic testing for breast-ovarian cancer susceptibility.
AB  - Previously, we have reported a clinical trial in which any woman in a defined
      geographic region who had a qualifying family history and who was referred by her
      physician or who was identified through a regional cancer registry was offered
      free genetic counseling, BRCA testing, and recommendations based on test results.
      Each family was represented by one affected and one unaffected person. Of the 87
      families actually tested, 13 were found to have deleterious mutations. To assess
      the impact of the counseling and testing process, we contacted the tested
      individuals 1 month and 1 year after receiving the test result and those with an
      abnormal test result after 4 years. Index subjects, we found, differed
      significantly from relatives. Before coming for counseling, index subjects
      perceived both their general health and emotional health as worse than did their
      relatives. After counseling and testing, index subjects continue to worry more
      about breast cancer than do relatives. Affected subjects, we found, differed
      significantly from unaffected subjects. Before counseling, affected subjects knew
      more about breast cancer, perceived their general health as poorer, and reported
      greater adherence to recommended breast cancer surveillance than did unaffected
      subjects. After counseling and testing, affected subjects were less satisfied
      than unaffected subjects with having been tested. This study indicates that the
      group most prone to distress by cancer risk genetic counseling and testing is not
      the recruited relatives, nor even those affected with cancer, but rather the
      index patients themselves. The index patients, i.e., the ones who want the risk
      information most, appear to undergo the most stress in obtaining it.

PMID- 15140370
TI  - Diagnostic genetic testing for hereditary breast and ovarian cancer in cancer
      patients: women's looking back on the pre-test period and a psychological
      evaluation.
AB  - The aim of this retrospective, exploratory study was to gain insight into how
      cancer patients who had a diagnostic genetic test for hereditary breast and/or
      ovarian cancer looked back on the pre-test period and to gain insight into the
      psychological impact of the genetic test result. Data were collected by
      semistructured interviews and self-report questionnaires in 19 BRCA1 or BRCA2
      mutation carriers, 7 noncarriers, and 36 patients with an inconclusive genetic
      test result. Cancer patients had a genetic test mainly for other persons,
      especially relatives in the descendant line. Mutation carriers felt more in
      control, but they also reported negative effects of genetic testing such as
      negative emotional impact and being concerned about their children. Non-carriers
      were relieved. The group of women where no BRCA1 or BRCA2 mutation was found in
      the family was heterogeneous. Some misinterpreted the genetic test result as
      revealing the absence of a genetic predisposition. Others were relieved but also
      still aware of an increased risk, whereas a last group experienced continuing
      uncertainty and felt less in control. Self-report questionnaires did not reveal
      differences in general and cancer-specific distress as a function of the genetic
      test result. Furthermore, no differences among the three groups were found
      regarding perceived seriousness of breast and ovarian cancer and perceived
      control of breast cancer. Perceived control of ovarian cancer was highest in the
      inconclusive group.

PMID- 15140371
TI  - Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known
      carriers: attributes, cancer worry, and barriers to testing in a multicenter
      clinical cohort.
AB  - BRCA1/2 test decliners/deferrers have received almost no attention in the
      literature and this is the first study of this population in the United Kingdom.
      The aim of this multicenter study is to examine the attributes of a group of
      individuals offered predictive genetic testing for breast/ovarian cancer
      predisposition who did not wish to proceed with testing at the time of entry into
      this study. This forms part of a larger study involving 9 U.K. centers
      investigating the psychosocial impact of predictive genetic testing for BRCA1/2.
      Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic
      testing were evaluated by questionnaire following genetic counseling. A total of
      34 individuals declined the offer of predictive genetic testing. Compared to the
      national cohort of test acceptors, test decliners are significantly younger.
      Female test decliners have lower levels of cancer worry than female test
      acceptors. Barriers to testing include apprehension about the result, traveling
      to the genetics clinic, and taking time away from work/family. Women are more
      likely than men to worry about receiving less screening if found not to be a
      carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a
      more vulnerable group in terms of cancer worry. However, barriers to testing need
      to be discussed in genetic counseling.

PMID- 15140372
TI  - Racial and ethnic variations in knowledge and attitudes about genetic testing.
AB  - This study was designed to shed light on whether differences in utilization of
      genetic testing by African-Americans, Latinos, and non-Hispanic Whites are due
      primarily to different preferences, or whether they instead reflect other values
      and beliefs or differential access. It explores the values, attitudes, and
      beliefs of African-Americans, Latinos, and non-Hispanic Whites with respect to
      genetic testing by means of a telephone survey of representative samples of these
      three groups. The study finds clear evidence that Latinos and African-Americans
      are, if anything, more likely to express preferences for both prenatal and adult
      genetic testing than White respondents. At the same time, they hold other beliefs
      and attitudes that may conflict with, and override, these preferences in specific
      situations. African-Americans and Latinos are also less knowledgeable about
      genetic testing than non-Hispanic Whites, and they are less likely to have the
      financial resources or insurance coverage that would facilitate access to
      testing.

PMID- 15140373
TI  - Diagnostic test for Y chromosome microdeletion screening in male infertility.
AB  - Despite the current lack of understanding the mechanism of deleterious effects of
      Y chromosome microdeletions and their prognostic influence on male subfertility,
      the Y chromosome microdeletion test is widely used in the diagnostic evaluation
      of male subfertility. However, currently used diagnostic schemes have not been
      sufficiently evaluated for their diagnostic performance. The purpose of this
      study was to analyze a large database of published Y chromosome microdeletions to
      develop the optimal screening strategy for male subfertility. Therefore, we
      created a database from genetic and clinical data published in 52 peer-reviewed
      studies reporting on 512 cases with Y chromosome microdeletions. We developed a
      computerized procedure with the goal of minimizing the number of genetic markers
      included in the diagnostic set while maximizing the detection rate in patients
      with microdeletions. We estimate that 85.6% of all published Y chromosome
      microdeletions can be covered by a set of six genetic markers (sY84, sY127,
      sY152, RBMY1, sY147, sY254-DAZ). Inclusion of additional markers brings
      relatively little to the sensitivity of the test and is potentially related to
      the population origin.

PMID- 15140374
TI  - Mutation carrier testing in Lesch-Nyhan syndrome families: HPRT mutant frequency
      and mutation analysis with peripheral blood T lymphocytes.
AB  - Mutations in the X chromosome hypoxanthine-guanine phosphoribosyl transferase
      (HPRT) gene are responsible for Lesch-Nyhan syndrome and related diseases in
      humans. Because the gene is on the X chromosome, males are affected and females
      in the families are at risk of being carriers of the mutation. Because there are
      so many different mutations that can cause the disease (218 different mutations
      in 271 families), genetic testing for carrier status of females requires detailed
      molecular analysis of the familial mutation. This analysis can be complicated by
      the unavailability of an affected male for study. In addition, when the mutation
      is a deletion (34 reported instances), molecular analysis in females is difficult
      because of the two X chromosomes. We have applied a peripheral blood T lymphocyte
      cloning assay that uses resistance to the purine analogue 6-thioguanine (TG) to
      measure the frequency of cells in females expressing a mutant HPRT allele to
      determine mutation carrier status in 123 females in 61 families. In families in
      which the HPRT mutation was determined and could be easily analyzed in samples
      from females, we found a mean (+/- SD) mutant frequency of 9.7 (+/- 8.7) x 10(-6)
      in noncarrier females and 2.9 (+/- 3.0) x 10(-2) in carrier females. The
      frequency in carrier females is less than the 0.5 expected for nonrandom X
      inactivation because of in vivo selection against HPRT mutation-expressing T
      lymphocytes or stem cells during prenatal development. The use of this cloning
      assay allows determination of the carrier status of females even when the HPRT
      mutation is not yet known or is difficult to determine in DNA samples from
      females. This approach provides a rapid assay that yields information on carrier
      status within 10 days of sample receipt.

PMID- 15140375
TI  - Reverse hybridization vs. DNA sequencing in the molecular diagnosis of Familial
      Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive inflammatory
      disorder predominantly affecting people living in or originating from areas
      around the Mediterranean Sea. It is caused by a number of mutations within the
      MEFV gene, which differently affect the severity of the disease phenotype.
      Because patients usually present with rather nonspecific clinical symptoms, MEFV
      genotyping can confirm and refine FMF diagnosis and improve treatment of affected
      individuals. We have performed a method comparison study on 100 Lebanese FMF
      patients to evaluate the potential of a rapid reverse-hybridization teststrip
      based assay (FMF StripAssay) to serve as a first-line screening test for our
      population. When results obtained by reverse-hybridization and DNA sequencing of
      exons 2, 3, 5, and 10 were compared, the FMF StripAssay identified 144/149
      mutations, and correctly typed all 12 different MEFV mutations covered. We
      conclude that reverse-hybridization provides a very rapid, accurate and easy-to
      perform screening method, and, in combination with more comprehensive diagnostic
      methods, represents an efficient strategy for FMF genotyping.

PMID- 15140376
TI  - Comparison of the validity of preimplantation genetic diagnosis for embryo
      chromosomal anomalies by fluorescence in situ hybridization on one or two
      blastomeres.
AB  - Is it necessary to analyze two blastomeres in preimplantation genetic diagnosis
      (PGD) by fluorescence in situ hybridization (FISH) or is one blastomere enough,
      as suggested by some teams? We analyzed the sensitivity (Se), specificity (Sp),
      positive predictive value (PPV), negative predictive value (NPV), false positives
      (FP), false negatives (FN), and the efficiency (Eff) of FISH performed on one
      (Group I) or two (Group II) blastomeres. Ninety embryos were analyzed (day 3), 19
      blastocysts were replaced (day 5), 64 embryos were reanalyzed (day 5), (Group I =
      23; Group II = 41). No differences were observed between the two groups for all
      of the parameters considered, but one false negative was observed in Group I.
      Furthermore, two embryos from Group II, which had a discordant diagnosis at PGD
      (one blastomere being normal and one abnormal), were read as abnormal after
      reanalysis. The accidental biopsy of the normal blastomere could have lead to the
      selection of these 2 embryos for transfer, causing a misdiagnosis rate of 4.8%.
      We conclude that embryo reanalysis is a useful tool to test the reliability of
      PGD in each laboratory: that PGD on two blastomeres is safer because the practice
      of PGD on one blastomere can result in a false-negative misdiagnosis.

PMID- 15140377
TI  - Prevalence of alleles associated with HIV resistance in Russia.
AB  - Genetic polymorphisms of CCR5, CCR2, and SDF1 genes have been associated with
      resistance during human immunodeficiency virus type 1 (HIV-1) infection and
      disease progression. In the present report, we studied the frequency and co
      occurrence of CCR5Delta32, CCR5-59029A/G, CCR2-64I, and SDF1-3'A allelic variants
      among HIV-1-seronegative individuals (n = 171) in Moscow. Observed allelic
      frequencies were 0.0906 [95% confidence interval (CI), 0.06-0.1212] for
      CCR5Delta32, 0.4072 (95% CI, 0.3542-0.4602) for CCR5-59029G, 0.1061 (95% CI,
      0.0728-0.1394) for CCR2-64I, and 0.2218 (95% CI 0.1715-0.2721) for SDF1-3'A. A
      significant linkage disequilibrium (p = 0.0034) between CCR2-64I and SDF1-3'A
      alleles was observed.

PMID- 15140379
TI  - A novel encoded particle technology that enables simultaneous interrogation of
      multiple cell types.
AB  - The authors have developed a cellular analysis platform, based on encoded
      microcarriers, that enables the multiplexed analysis of a diverse range of
      cellular assays. At the core of this technology are classes of microcarriers that
      have unique, identifiable codes that are deciphered using CCD-based imaging and
      subsequent image analysis. The platform is compatible with a wide variety of
      cellular imaging-based assays, including calcium flux, reporter gene activation,
      cytotoxicity, and proliferation. In addition, the platform is compatible with
      both colorimetric and fluorescent readouts. Notably, this technology has the
      unique ability to multiplex different cell lines in a single microplate well,
      enabling scientists to perform assays and data analysis in novel ways.

PMID- 15140380
TI  - Miniaturization of whole live cell-based GPCR assays using microdispensing and
      detection systems.
AB  - Cell-based beta-lactamase reporter gene assays designed to measure the functional
      responses of G-protein-coupled receptors (GPCRs) were miniaturized to less than 2
      microL total assay volume in a 3456-well microplate. Studies were done to
      evaluate both receptor agonists and antagonists. The pharmacology of agonists and
      antagonists for target GPCRs originally developed in a 96-well format was
      recapitulated in a 3456-well microplate format without compromising data quality
      or EC(50)/IC(50) precision. These assays were employed in high-throughput
      screening campaigns, allowing the testing of more than 150,000 compounds in 8 h.
      The instrumentation used and practical aspects of the assay development are
      discussed.

PMID- 15140381
TI  - Multiplex GPCR assay in reverse transfection cell microarrays.
AB  - G protein-coupled receptors (GPCRs) are a superfamily of proteins that include
      some of the most important drug targets in the pharmaceutical industry. Despite
      the success of this group of drugs, there remains a need to identify GPCR
      targeted drugs with greater selectivity, to develop screening assays for
      validated targets, and to identify ligands for orphan receptors. To address these
      challenges, the authors have created a multiplexed GPCR assay that measures
      greater than 3000 receptor: ligand interactions in a single microplate. The
      multiplexed assay is generated by combining reverse transfection in a 96-well
      plate format with a calcium flux readout. This assay quantitatively measures
      receptor activation and inhibition and permits the determination of compound
      potency and selectivity for entire families of GPCRs in parallel. To expand the
      number of GPCR targets that may be screened in this system, receptors are
      cotransfected with plasmids encoding a promiscuous G protein, permitting the
      analysis of receptors that do not normally mobilize intracellular calcium upon
      activation. The authors demonstrate the utility of reverse transfection cell
      microarrays to GPCR-targeted drug discovery with examples of ligand selectivity
      screening against a panel of GPCRs as well as dose-dependent titrations of
      selected agonists and antagonists.

PMID- 15140382
TI  - Use of surface plasmon-coupled emission to measure DNA hybridization.
AB  - The authors describe a new approach to measuring DNA hybridization based on
      surface plasmon-coupled emission (SPCE). SPCE is the resonance coupling of
      excited fluorophores with electron motions in thin metal films, resulting in
      efficient transfer of energy through the film and radiation into the glass
      substrate. The authors evaluated the use of SPCE for detection of DNA
      hybridization. An unlabeled capture biotinylated oligonucleotide was attached
      near the surface of a thin (50 nm) silver film using streptavidin. The authors
      then measured the emission intensity of single-stranded Cy5-labeled DNA upon
      binding to a complementary oligomer attached to a silver film. Hybridization
      could be detected by an increase in SPCE, which appeared as light radiated into
      the substrate at a sharply defined angle near 73 degrees from the normal. The
      largest signals were observed when the excitation angle of incidence equaled the
      surface plasmon wavelength, but directional emission was also observed without
      excitation by the surface plasmon evanescent field. The increased intensity is
      due to proximity to the metal surface, so that hybridization can be detected
      without a change in the quantum yield of the fluorophore. These results indicate
      that SPCE can provide highly sensitive real-time measurement of DNA
      hybridization.

PMID- 15140383
TI  - An automated image capture and quantitation approach to identify proteins
      affecting tumor cell proliferation.
AB  - To facilitate the characterization of proteins that negatively regulate tumor
      cell proliferation in vitro, the authors have implemented a high-throughput
      functional assay that measures S-phase progression of tumor cell lines. For 2
      tumor cell lines-human melanoma A375 and human lung carcinoma A549-conditions
      were established using the cyclin-dependent kinase inhibitor, p27kip; the tumor
      suppressor p53, a kinase-inactive allele of the cell cycle-regulated
      serine/threonine kinase Aurora2; and the G1/S drug block, aphidicolin. For
      screening purposes, gene libraries were delivered by adenoviral infection. Cells
      were fixed and labeled by immunocytochemistry, and an automated image acquisition
      and analysis package on a Cellomics ArrayScanII was used to quantify the effects
      of these treatments on cell proliferation. The assay can be used to identify
      novel proteins involved in proliferation and serves as a more robust,
      reproducible, and sensitive alternative to enzyme-linked immunosorbent assay
      (ELISA)-based technologies.

PMID- 15140384
TI  - A homogeneous, nonradioactive high-throughput fluorogenic protein phosphatase
      assay.
AB  - Protein phosphatases are critical components in cellular regulation; they do not
      only act as antioncogenes by antagonizing protein kinases, but they also play a
      positive regulatory role in a variety of cellular processes that require
      dephosphorylation. Thus, assessing the function of these enzymes necessitates the
      need for a robust, sensitive assay that accurately measures their activities. The
      authors present a novel, homogeneous, and nonradioactive assay to measure the
      enzyme activity of low concentrations of several protein phosphatases
      (phosphoserine/phosphothreonine phosphatases and phosphotyrosine phosphatases).
      The assay is based on the use of fluorogenic peptide substrates (rhodamine 110,
      bis-phosphopeptide amide) that do not fluoresce in their conjugated form, which
      is resistant to cleavage by aminopeptidases. However, upon dephosphorylation by
      the phosphatase of interest, the peptides become cleavable by the protease and
      release the highly fluorescent-free rhodamine 110. The assay is rapid, can be
      completed in less than 2 h, and can be carried out in multiwell plate formats
      such as 96-, 384-, and 1536-well plates. The assay has an excellent dynamic
      range, high signal-to-noise ratio, and a Z' of more than 0.8, and it is easily
      adapted to a robotic system for drug discovery programs targeting protein
      phosphatases.

PMID- 15140388
TI  - Characterization of beta-lactamases responsible for resistance to extended
      spectrum cephalosporins in Escherichia coli and Salmonella enterica strains from
      food-producing animals in the United Kingdom.
AB  - Nine epidemiologically unrelated isolates [1 Salmonella Bredeney from turkeys,
      and 8 Escherichia coli [3 environmental isolates (2 from chickens, 1 from pigs),
      and 5 isolates from cattle with neonatal diarrhea]] were examined both pheno- and
      genotypically for extended-spectrum beta-lactam (ESBL) resistance. Resistance
      phenotypes (ampicillin, aztreonam, cefotaxime, cefpodoxime, ceftazidime, and
      ceftriaxone) suggested the presence of an ESBL enzyme, but cefoxitin MICs (>/= 32
      mg/L) suggested the presence of an AmpC-like enzyme. Synergism experiments with
      benzo(b)thiophene-2-boronic acid (BZBTH2B) and isoelectric focusing (IEF)
      revealed the presence of an AmpC beta-lactamase with a pI >/= 9. amp C multiplex
      PCR, sequence, and Southern analyses indicated that only the Salmonella isolate
      had a plasmid-encoded AmpC beta-lactamase CMY-2 on a nonconjugative 60-MDa
      plasmid. PCR and sequence analysis of the E. coli ampC promoter identified
      mutations at positions -88(T), -82(G), -42(T), -18(A), -1(T) and +58(T) in all
      the isolates. In addition one strain had two extra-mutations at positions +23(A)
      and +49(G), and another strain had one extra-mutation at position +32(A). DNA
      fingerprinting revealed that all the E. coli isolates were different clones. It
      also showed that the U.K. Salmonella isolate was indistinguisable from a Canadian
      Salmonella isolate from turkeys; both had identical resistance phenotypes and
      produced CMY-2. This is the first report of a CMY-2 Salmonella isolate in the
      United Kingdom. These data imply that beta-lactam resistance in animal isolates
      can be generated de novo as evidenced by the E. coli strains, or in the case of
      the Salmonella strains be the result of intercontinental transmission due to an
      acquired resistance mechanism.

PMID- 15140389
TI  - Phylogeny of efflux-mediated tetracycline resistance genes and related proteins
      revisited.
AB  - A SRS search in the GenBank/EMBL databases for entire genes encoding efflux
      mediated resistance allocated to a recognized tetracycline determinant revealed
      the existence of at least 87 genes. DNA-based and protein sequence analyses of
      representatives from the different efflux-mediated tetracycline determinant
      groups were performed and allowed us to propose a revision of the current
      grouping on the basis of our new evolutionary trees. On the other hand,
      similarity, topology, and hydropathy analyses of some representatives from 12
      transmembrane segments (TMS) and 14-TMS proteins lead us to perform meaningful
      sequence alignments of recognized or putative 12-TMS and 14-TMS proteins
      truncated to their first 200 amino acids (alpha-domain of the protein). For all
      aligned truncated proteins, including old and recently discovered tetracycline
      resistance determinants, significant similarities along this segment were
      demonstrated and three new conserved motifs identified, reinforcing the
      hypothesis of a common ancestry for the alpha-domain of all tetracycline-efflux
      pumps.

PMID- 15140390
TI  - Integron-associated antibiotic resistance in enteroaggregative and enteroinvasive
      Escherichia coli.
AB  - Ten enteroinvasive (EIEC) and 25 enteroaggregative (EaggEC) E. coli strains
      isolated from Senegalese patients were analyzed for their integron content. All
      strains were resistant to at least two antibiotics. Four EIEC and 15 EaggEC were
      found to carry a class 1 integron. An identical integron carrying a single dfrA5
      cassette, conferring resistance to trimethoprim, was identified in all four EIEC
      strains. Five EaggEC strains harbored an integron with a single cassette, dfrA7,
      while the remaining 10 strains carried two integrons, one with a single cassette,
      aadA1a conferring resistance to streptomycin and spectinomycin, and the second
      one bearing two cassettes, dfrA13 and oxa5, the later being a beta-lactam
      resistance cassette. The presence of these integrons is worrying, because
      trimethoprim is largely used for diarrheal disease therapy in Africa. Thus, the
      presence of integrons in diarrheagenic strains is of public health importance
      because a limited number of antibiotics are available in developing countries.

PMID- 15140391
TI  - Streptococcus agalactiae in a large Portuguese teaching hospital: antimicrobial
      susceptibility, serotype distribution, and clonal analysis of macrolide-resistant
      isolates.
AB  - Group B streptococci are emerging as a cause of serious infection worldwide. The
      capsular polysaccharides are not only important virulence factors but also the
      target of vaccine development efforts. Serotypes III (24.6%), V (23.4%), Ia
      (17.8%), and II (16.3%) were the most prevalent among 252 Streptococcus
      agalactiae isolates collected during 1999-2002 in the largest hospital of Lisbon,
      Portugal. The substantial proportion of bacteremic patients (17 neonates and 21
      adults) in this period illustrates the present importance of S. agalactiae as a
      cause of invasive disease. All isolates were fully susceptible to penicillin
      (MIC(50) = 0.064 microg/ml; MIC(90) = 0.094 microg/ml, range 0.008-0.094),
      cefotaxime, chloramphenicol, ofloxacin, and vancomycin. Resistance was found to
      tetracycline (75.4%), erythromycin (10.7%), and clindamycin (9.9%). Of the 27
      erythromycin-resistant isolates, 70.4% had the cMLS(B), 22.2% the iMLS(B), and
      7.4% the M phenotype. All isolates presenting the M phenotype carried the mef(A)
      gene, whereas the erm(B) gene was found in a large fraction of MLS(B) isolates (n
      = 17) and only a small proportion (n = 7) the erm(A) gene [erm(TR) variant]. All
      isolates carried a single macrolide-resistance determinant. Macrolide resistance
      was not attributable to a single clone as evidenced by distinct serotype and
      pulsed-field gel electrophoretic profiles. Careful surveillance of S. agalactiae
      invasive infections in Portugal is essential, and the treatment or intrapartum
      prophylaxis of patients who are allergic to penicillin should be guided by
      contemporary resistance patterns observed in the country.

PMID- 15140392
TI  - Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from
      Asian countries: ANSORP study.
AB  - Seventeen clinical isolates of Streptococcus pneumoniae showing reduced
      susceptibility to ciprofloxacin (MIC >/= 4 micro g/ml) collected from eight
      different Asian countries were analyzed by antimicrobial susceptibility,
      serotyping, pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the
      quinolone resistance-determining regions (QRDRs) in gyrA, gyrB, parC, and parE.
      All isolates but one showed more than one amino acid alteration in QRDRs of four
      responsible genes. Ile460 --> Val in parE was the most common mutation. Data
      suggest that Lys137 --> Asn in parC may be a primary step in the development of
      high-level and multiple FQ resistance. An additional mutation of Ser81 --> Phe in
      gyrA resulted in high-level resistance to ciprofloxacin, levofloxacin, and
      gatifloxacin, whereas Ser79 --> Phe in parC may exert an important role in the
      development of moxifloxacin resistance. Two novel amino acid changes in gyrB,
      Ala390 --> Val and Asn423 --> Thr, were found. Data from PFGE suggest an
      introduction and local spread of multiple resistant Spain(23F)-1 clone in Hong
      Kong, but isolates from other Asian countries were not related to this clone.

PMID- 15140393
TI  - Identification of a variant "Rome clone" of methicillin-resistant Staphylococcus
      aureus with decreased susceptibility to vancomycin, responsible for an outbreak
      in an intensive care unit.
AB  - We describe the identification of a variant of the "Rome clone" of methicillin
      resistant Staphylococcus aureus (MRSA), responsible for an outbreak involving 5
      patients in a Cardiac Surgery Intensive Care Unit (CS-ICU) of a tertiary-care
      University Hospital in Rome. All strains isolated from patients and from nasal
      swabs obtained from four members of the CS-ICU personnel, belonged to the same
      identified clone. The characteristics of this clone were: (1) resistance to
      ampicillin, oxacillin, gentamicin, ciprofloxacin, erythromycin, clindamycin,
      rifampin, spectinomycin, and tetracycline; (2) vancomycin and teicoplanin MICs
      respectively of 2 and 4 mg/L; (3) heteroresistant subpopulations in the presence
      of 4 and 6 mg/L of vancomycin (10(-3) and 10(-5), respectively); (4) clonal type
      I::J::C determined following an established protocol (mec A::Tn 554 ::PFGE); (5)
      sequence type ST247 (3-3-1-12-4-4-16), obtained by multilocus sequence typing
      (MLST); and (6) the staphylococcal cassette chromosome mec (SCC) IA, obtained by
      multiplex PCR method. This new strain had different characteristics from the
      epidemic clone circulating in the same hospital from 1997 and designed "Rome
      clone," which was susceptible to erythromycin, clindamycin, and spectinomycin and
      belonged to the II::NH::C genetic background. A high genetic similarity between
      this Rome clone and the previously classified Archaic and Iberian clones was
      found, because they shared the same allelic profile (ST247), probably originating
      from the same S. aureus ancestor of the Iberian MRSA strains. Therefore, the
      strains responsible for the outbreak, with vancomycin MICs 2-4 mg/L, are variant
      clones, showing the genotype of the "Rome clone," the ST247 in association with
      SCC mec type IA (ST247-MRSA-IA), and are characterized by a uniform
      susceptibility to fosfomycin.

PMID- 15140395
TI  - Antimicrobial susceptibility of equine and environmental isolates of Clostridium
      difficile.
AB  - The antimicrobial susceptibility of 50 Clostridium difficile isolates, 36 of them
      from horse feces and 14 from environmental sites, was determined by broth
      microdilution. The antimicrobial agents tested were avilamycin, cephalothin,
      chloramphenicol, clindamycin, erythromycin, gentamicin, neomycin, oxacillin,
      oxytetracycline, penicillin, spiramycin, streptomycin,
      trimethoprim/sulfamethoxazole, vancomycin, and virginiamycin. All isolates were
      susceptible to vancomycin (MIC </=1 microg/ml). The MICs of erythromycin,
      oxytetracycline, spiramycin, and virginiamycin showed a bimodal distribution.
      Compared with the majority of isolates, the MICs of erythromycin (MIC > 16
      microg/ml), oxytetracycline (MIC >/=32 microg/ml), spiramycin (MIC > 16
      microg/ml), and virginiamycin (MIC 8-16 microg/ml) were higher for 18 isolates.
      Those were mainly isolated from horses at animal hospitals and further from
      environmental sites at a stud farm. In contrast, all isolates, except one, from
      healthy foals had low MICs of erythromycin, spiramycin, virginiamycin, and
      oxytetracycline. The isolates from soil in public parks had also low MICs of
      these antimicrobial agents. Broth microdilution appeared both reliable and
      reproducible for susceptibility testing of C. difficile. The method was also
      readily performed and the MIC endpoints were easily read.

PMID- 15140394
TI  - Antimicrobial resistance and serotype prevalence of Salmonella isolated from
      dairy cattle in the southwestern United States.
AB  - Mature dairy cattle were sampled over a 2-year period (2001-2002) on six farms in
      New Mexico and Texas. Fecal samples (n = 1560) were collected via rectal
      palpation and cultured for Salmonella, and one isolate from each positive sample
      was serotyped. Three isolates of each serotype, with the exception of Salmonella
      Newport (n = 12), were examined for susceptibility to 17 antimicrobial agents.
      Twenty-two different serotypes were identified from a total of 393 Salmonella
      isolates. Montevideo was the predominant serotype (27%) followed by Mbandaka
      (15%), Senftenberg (11.4%), Newport (6.4%), Anatum (4.8%), and Give (4.8%).
      Salmonella Typhimurium and Dublin, two frequently reported serotypes, accounted
      for only 1% of the observed serotypes in this study. Sixty-four percent of the
      serotypes were susceptible to all 17 antimicrobials, 14% were resistant to a
      single agent, and 22% were multiresistant (2-11 types of resistance). All
      isolates tested were susceptible to amikacin, apramycin, imipenem, ceftriaxone,
      nalidixic acid, and ciprofloxacin. The most frequent types of resistance were to
      sulfamethoxazole, tetracycline, streptomycin, kanamycin, chloramphenicol, and
      ampicillin (ranging from 8.9 to 22.4%). Serotypes demonstrating multiple
      resistance included Dublin and Give (resistant to three or more antibiotics),
      Typhimurium (resistant to five antibiotics), and Newport (four and two isolates
      resistant to six and nine antibiotics, respectively). Class 1 integrons were
      present in only two Salmonella Dublin isolates and one Salmonella Newport
      isolate. The most prevalent resistance patterns observed in this study were
      toward antimicrobial agents commonly used in cattle, while all Salmonella
      isolates were susceptible to ceftriaxone and ciprofloxacin, antibiotics used in
      human medicine.

PMID- 15140396
TI  - Antibiotic resistance among fecal indicator bacteria from healthy individually
      owned and kennel dogs.
AB  - Escherichia coli and Enterococcus faecalis strains isolated from anal swabs of
      clinically healthy dogs were examined for the presence of acquired antimicrobial
      resistance. The strains originated from dogs of 92 different owners and from
      eight breeding kennels. The purpose of the present study was to evaluate the
      resistance situation in the intestinal flora of the dog to assess the possible
      role of the dog flora as a reservoir of antimicrobial resistance. Multiple
      resistance was rarely found in E. coli strains collected from individually owned
      dogs, in contrast with strains from kennel dogs. Resistance to ampicillin,
      trimethoprim, and sulfamethoxazole was significantly less prevalent in E. coli
      from privately owned dogs than in strains from kennel dogs. Resistance rates
      against tetracycline and macrolides were unexpectedly high in E. faecalis
      strains. Two and three E. faecalis strains from individually owned dogs and
      kennel dogs, respectively, were resistant to gentamicin, an antibiotic often used
      for treating enterococcal infections in humans. This study demonstrates that
      resistance percentages may fluctuate with the choice of dog population. The
      observed antimicrobial resistance percentages indicate that the flora of healthy
      dogs may act as a reservoir of resistance genes.

PMID- 15140397
TI  - Risk Factors for Ciprofloxacin Resistance in Bloodstream Infections Due to
      Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella
      pneumoniae.
AB  - The present study was conducted to identify risk factors for ciprofloxacin
      resistance in bloodstream infections due to extended-spectrum beta -lactamase
      producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production
      was determined in stored E. coli and K. pneumoniae blood isolates from January,
      1998, to December, 2002, by National Committee for Clinical Laboratory Standards
      (NCCLS) guidelines and/or double-disk synergy test. Antimicrobial susceptibility
      was determined by the disk diffusion test method. A total of 133 patients with
      ESBL-EK bacteremia were analyzed retrospectively. A total of 80 (60.2%) patients
      experienced bacteremia due to strains resistant to ciprofloxacin. There were no
      significant differences in age, sex, and APACHE II score between the
      ciprofloxacin-resistant group (CIP-R) and-susceptible group (CIPS). The most
      common primary site of infection in CIP-R was pancreaticobiliary tract infection
      (46/80, 57.5%) and that in CIP-S was unknown primary site (23/53, 43.4%).
      Independent risk factors for ciprofloxacin resistance were: prior use of
      fluoroquinolones (OR, 5.53; 95% CI, 1.56-25.42, p = 0.032), indwelling urinary
      catheter (OR, 3.68; 95% CI, 1.27-10.67, p = 0.017), and invasive procedure within
      72 hr prior to bacteremia (OR, 4.03; 95% CI, 1.44-11.25, p = 0.008). Our data
      suggest that strategies designed to reduce the ciprofloxacin resistance rate in
      ESBL-EK strains should focus on limiting the use of fluoroquinolones and
      minimizing invasive procedures, including insertion of a urinary catheter.

PMID- 15140398
TI  - A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent
      probe.
AB  - Here we describe a novel method for imaging apoptosis in cells using a near
      infrared fluorescent (NIRF) probe selective for caspase-1 (interleukin 1beta
      converting enzyme, ICE). This biocompatible, optically quenched ICE-NIRF probe
      incorporates a peptide substrate, which can be selectively cleaved by caspase-1,
      resulting in the release of fluorescence signal. The specificity of this probe
      for caspase-1 is supported by various lines of evidence: 1) activation by
      purified caspase-1, but not another caspase in vitro; 2) activation of the probe
      by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-lacZ)
      expressing a catalytically active caspase-1-lacZ fusion protein; 3) inhibition of
      HGC-ICE-lacZ vector-induced activation of the probe by coincubation with the
      caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4)
      activation of the probe following standard methods of inducing apoptosis with
      staurosporine, ganciclovir, or ionizing radiation in culture. These results
      indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and
      vector-expressed caspase-1 activity in cells. Furthermore, tumor implant
      experiments indicate that this ICE-NIRF probe can be used to detect caspase-1
      activity in living animals. This novel ICE-NIRF probe should prove useful in
      monitoring endogenous and vector-expressed caspase-1 activity, and potentially
      apoptosis in cell culture and in vivo.

PMID- 15140399
TI  - Interleukin-12 inhibits tumor growth in a novel angiogenesis canine
      hemangiosarcoma xenograft model.
AB  - We established a canine hemangiosarcoma cell line derived from malignant
      endothelial cells comprising a spontaneous tumor in a dog to provide a renewable
      source of endothelial cells for studies of angiogenesis in malignancy. Pieces of
      the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse
      allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from
      the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF)
      receptors 1 and 2, CD31, CD146, and alpha(v)beta(3) integrin, and produced
      several growth factors and cytokines, including VEGF, basic fibroblast growth
      factor, and interleukin (IL)-8 that are stimulatory to endothelial cell growth.
      These results indicated that the cells recapitulated features of mitotically
      activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic
      responses in mice and formed tumor masses composed of aberrant vascular channels
      in immunocompromised mice providing novel opportunities for investigating the
      effectiveness of antiangiogenic agents. Using this model, we determined that IL
      12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed
      angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell
      model we have described offers unique opportunities to pursue further
      investigations with IL-12, as well as other antiangiogenic approaches in cancer
      therapy.

PMID- 15140400
TI  - A theoretical model for intraperitoneal delivery of cisplatin and the effect of
      hyperthermia on drug penetration distance.
AB  - A theoretical model for the intraperitoneal (i.p.) delivery of cisplatin and heat
      to tumor metastases in tissues adjacent to the peritoneal cavity is presented.
      The penetration distance (the depth to which drug diffuses directly from the
      cavity into tissues) is predicted to be on the order of 0.5 mm. The model shows
      that exchange with the microvasculature has more effect than cellular uptake in
      limiting the penetration distance. Possible effects of hyperthermia are
      simulated, including increased cell uptake of drug, increased cell kill at a
      given level of intracellular drug, and decreased microvascular density. The model
      suggests that the experimental finding of elevated intracellular platinum levels
      up to a depth of 3 to 5 mm when drug is delivered i.p. by a heated infusion
      solution is due to penetration of heat to this distance, causing increased cell
      uptake of drug. Beyond a depth of about 0.5 mm, the drug is delivered mainly
      through the circulation. Use of sodium thiosulfate to deactivate systemic
      cisplatin may therefore be counterproductive when heat is delivered locally. The
      model suggests that i.p. delivery of heat, combined with systemic delivery of
      drug, may be as effective as i.p. delivery of heat and drug.

PMID- 15140402
TI  - Pretreatment prediction of brain tumors' response to radiation therapy using high
      b-value diffusion-weighted MRI.
AB  - Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues'
      biophysical characteristics, including apparent diffusion coefficients (ADCs) and
      volume fractions of water in different populations. In this work, we evaluate the
      clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging
      (HDWMRI), acquired up to b = 4000 sec/mm(2) to amplify sensitivity to water
      diffusion properties, in pretreatment prediction of brain tumors' response to
      radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring
      enhancing lesions were excluded due to their distinct diffusion characteristics.
      Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was
      determined from relative changes in tumor volumes calculated from contrast
      enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning
      therapy. ADCs and a diffusion index, R(D), reflecting tissue viability based on
      water diffusion were calculated from DWMRIs. Pretreatment values of ADC and R(D)
      were found to correlate significantly with later tumor response/nonresponse (r =
      0.76, P <.002 and r = 0.77, P <.001). This correlation implies that tumors with
      low pretreatment diffusion values, indicating high viability, will respond better
      to radiotherapy than tumors with high diffusion values, indicating necrosis.
      These results demonstrate the feasibility of using DWMRI for pretreatment
      prediction of response to therapy in patients with brain tumors undergoing
      radiotherapy.

PMID- 15140401
TI  - Methylation of a CpG island within the uroplakin Ib promoter: a possible
      mechanism for loss of uroplakin Ib expression in bladder carcinoma.
AB  - Uroplakin Ib is a structural protein on the surface of urothelial cells.
      Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell
      carcinomas (TCCs) but molecular mechanisms underlying loss of expression remain
      to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG
      island spanning the proximal promoter, exon 1, and the beginning of intron 1.
      This study examined the hypothesis that methylation of this CpG island regulates
      uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse
      transcription polymerase chain reaction and CpG methylation was assessed by
      bisulfite modification of DNA, PCR, and sequencing. A correlation was
      demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG
      methylation. In support of a regulatory role for methylation, incubating
      uroplakin Ib-negative lines with 5-aza-2'-deoxycytidine reactivated uroplakin Ib
      mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation
      was also observed in normal urothelium and bladder carcinomas. In particular,
      loss of uroplakin Ib expression correlated with methylation of a putative
      Sp1/NFkappaB binding motif. The data are consistent with the hypothesis that
      methylation of specific sites within the uroplakin Ib promoter may be an
      important factor in the loss of uroplakin Ib expression in TCCs.

PMID- 15140403
TI  - Clustering of molecular alterations in gastroesophageal carcinomas.
AB  - Gene expression levels are regulated at many levels. Integration of genome-wide
      analyses for the study of DNA and RNA provides a unique tool to detect genetic
      alterations in the cancer genome. In this study, we generated and integrated DNA
      amplification data from comparative genomic hybridization (CGH) and serial
      analyses of gene expression (SAGE) in order to obtain a molecular profile of
      gastroesophageal junction (GEJ) carcinomas. DNA amplifications mapped to specific
      chromosomal regions and were frequently seen at 1q, 4q, 5q, 6p, 7p, 8q, 17q, and
      20q. Using SAGE, we obtained over 156,432 tags from GEJ adenocarcinomas and
      normal gastric mucosa. These tags were assigned to UniGene clusters. Chromosomal
      positions for overexpressed genes were obtained to produce a GEJ carcinoma
      transcriptome map. A total of 123 genes was significantly overexpressed (more
      than fivefold; P <.01) in one or more SAGE libraries. This gene overexpression
      map was integrated and compared to the chromosomal CGH ideogram. Several
      chromosomal arms that had frequent DNA amplifications showed frequent gene
      expression alterations such as chromosomes 1 (15 genes), 2 (9 genes), 6 (6
      genes), 11 (6 genes), 12 (8 genes), and 17 (13 genes). Despite the relatively
      large DNA amplification regions, overexpressed genes frequently mapped and
      clustered to small chromosomal regions at early-replicating (Giemsa light) bands
      such as 1q21.3 (nine genes), 6p21.3 (five genes), and 17q21 (eight genes). These
      results provide a comprehensive tool to search for DNA amplifications and
      overexpressed genes in GEJ carcinoma. The observed phenomenon of the presence of
      large amplification areas, yet clustering of overexpressed genes to relatively
      small loci, may suggest a high organization of chromatin and cancer-related genes
      in the nucleus.

PMID- 15140404
TI  - Single dose of the antivascular agent, ZD6126 (N-acetylcolchinol-O-phosphate),
      reduces perfusion for at least 96 hours in the GH3 prolactinoma rat tumor model.
AB  - Tumor vasculature is an attractive therapeutic target as it differs structurally
      from normal vasculature, and the destruction of a single vessel can lead to the
      death of many tumor cells. The effects of antivascular drugs are frequently short
      term, with regrowth beginning less than 24 hours posttreatment. This study
      investigated the duration of the response to the vascular targeting agent,
      ZD6126, of the GH3 prolactinoma, in which efficacy and dose-response have
      previously been demonstrated. GH3 prolactinomas were grown in the flanks of eight
      Wistar Furth rats. All animals were treated with 50 mg/kg ZD6126. The tumors were
      examined with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) 24
      hours pretreatment and posttreatment, and at a single time between 48 and 96
      hours posttreatment. No evidence of recovery of perfusion was observed even at
      the longest (96-hour) time point. Involvement of a statistician at the project
      planning stage and the use of DCE-MRI, which permits noninvasive quantitation of
      parameters related to blood flow in intact animals, allowed this highly
      significant result to be obtained using only eight rats.

PMID- 15140405
TI  - Regulation of microtubule, apoptosis, and cell cycle-related genes by taxotere in
      prostate cancer cells analyzed by microarray.
AB  - Taxotere showed antitumor activity against solid tumors including prostate
      cancer. However, the molecular mechanism(s) of action of Taxotere has not been
      fully elucidated. In order to establish such molecular mechanism(s) in both
      hormone-insensitive (PC3) and hormone-sensitive (LNCaP) prostate cancer cells,
      comprehensive gene expression profiles were obtained by Affymetrix Human Genome
      U133A Array. The RNA from the cells treated with 2 nM Taxotere was subjected to
      microarray analysis. We found that a total of 166, 365, and 1785 genes showed
      greater than two-fold change in PC3 cells after 6, 36, and 72 hours of treatment,
      respectively compared to 57, 823, and 964 genes in LNCaP cells. The expression of
      tubulin was decreased, whereas the expression of microtubule-associated proteins
      was increased in Taxotere-treated prostate cancer cells, confirming the
      microtubule-targeting effect of Taxotere. Clustering analysis showed
      downregulation of some genes for cell proliferation and cell cycle. In contrast,
      Taxotere upregulated some genes that are related to induction of apoptosis and
      cell cycle arrest. From these results, we conclude that Taxotere caused
      alterations of a large number of genes, many of which may contribute to the
      molecular mechanism(s) by which Taxotere affects prostate cancer cells. Further
      molecular studies are needed in order to determine the cause and effect
      relationships between these genes altered by Taxotere. Nevertheless, our results
      could be further exploited for devising strategies to optimize therapeutic
      effects of Taxotere for the treatment of prostate cancer.

PMID- 15140406
TI  - Analysis of mammalian septin expression in human malignant brain tumors.
AB  - Septins are a highly conserved subfamily of GTPases that play an important role
      in the process of cytokinesis. To increase our understanding of the expression
      and localization of the different mammalian septins in human brain tumors, we
      used antibodies against septins 2, 3, 4, 5, 6, 7, 9, and 11 in immunofluorescence
      and Western blot analyses of astrocytomas and medulloblastomas. We then
      characterized the expression and subcellular distribution of the SEPT2 protein in
      aphidicolin-synchronized U373 MG astrocytoma cells by immunofluorescence and
      fluorescence-activated cell sorter analysis. To determine the role of SEPT2 in
      astrocytoma cytokinesis, we inducibly expressed a dominant-negative (DN) SEPT2
      mutant in U373 MG astrocytoma cells. We show variable levels and expression
      patterns of the different septins in brain tissue, brain tumor specimens, and
      human brain tumor cell lines. SEPT2 was abundantly expressed in all brain tumor
      samples and cell lines studied. SEPT3 was expressed in medulloblastoma specimens
      and cell lines, but not in astrocytoma specimens or cell lines. SEPT2 expression
      was cell cycle-related, with maximal levels in G2-M. Immunocytochemical analysis
      showed endogenous levels of the different septins within the perinuclear and
      peripheral cytoplasmic regions. In mitosis, SEPT2 was concentrated at the
      cleavage furrow. By immunocytochemistry and flow cytometry, we show that a DN
      SEPT2 mutant inhibits the completion of cell division and results in the
      accumulation of multinucleated cells. These results suggest that septins are
      variably expressed in human brain tumors. Stable expression of the DN SEPT2
      mutant leads to a G2-M cell cycle block in astrocytoma cells.

PMID- 15140409
TI  - Airway nitrergic pathways: is there therapeutic potential in asthma and COPD?
AB  - Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD)
      are characterised by airway hyperresponsiveness, epithelial damage, oxidative
      stress and airway inflammation. Inflammatory cells, including macrophages,
      neutrophils, eosinophils and lymphocytes, are crucial in the pathogenesis of
      asthma and COPD. The prevalence of asthma and COPD is increasing, especially in
      Western countries. Symptomatic treatment is based on reduction of airway
      obstruction by inhalation of beta(2)-receptor agonists and attenuation of the
      underlying inflammatory reactions by inhalation of corticosteroids. Because these
      agents only suppress symptoms, there is a need for medicines that remove the
      cause of these airway diseases.

PMID- 15140407
TI  - WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling
      in inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is the most lethal form of locally advanced
      breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and
      that it has growth- and angiogenesis-inhibitory functions in breast cancer in
      vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that
      belongs to the CCN family. It contains a signal peptide at the N-terminus and
      four highly conserved motifs. Here, for the first time, we investigate the
      function of WISP3 protein in relationship to its structural features. We found
      that WISP3 is secreted into the conditioned media and into the lumens of normal
      breast ducts. Once secreted, WISP3 was able to decrease, directly or through
      induction of other molecule(s), the IGF-1-induced activation of the IGF-IR, and
      two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC
      cells. Furthermore, WISP3 containing conditioned media decreased the growth rate
      of SUM149 cells. This work sheds light into the mechanism of WISP3 function by
      demonstrating that it is secreted and that, once in the extracellular media, it
      induces a series of molecular events that leads to modulation of IGF-IR signaling
      pathways and cellular growth in IBC cells.

PMID- 15140410
TI  - Purinergic signalling in the lung: important in asthma and COPD?
AB  - During the past decade, evidence has accumulated for the involvement of purines
      and purine receptors in the pathogenesis and pathophysiology of asthma and
      chronic obstructive pulmonary diseases. In particular, the indirect
      bronchospasmic and inflammatory actions of purines via the activation and
      degranulation of mast cells has been extensively studied and reviewed. At
      present, interest is focused on the impact of purines on pulmonary innervation
      and the neuroendocrine system, and the potent interaction of the latter with many
      of the airway components that are essentially altered in asthma and chronic
      obstructive pulmonary disease. However, data related to these interactions are
      diverse and not always easily recognised in the literature.

PMID- 15140411
TI  - Calcitonin gene-related peptide: role in airway homeostasis.
AB  - The lung is an important source of sensory neuropeptides that modulate airway
      function in health and disease. Among these neuropeptides, calcitonin gene
      related peptide (CGRP) plays a prominent role. CGRP is constitutively expressed
      in normal lungs where it localizes to a specialized subset of epithelial cells
      (neuroendocrine cells) and sensory C fibers distributed to pulmonary airways,
      blood vessels and lymphoid tissue. CGRP can mediate multiple effects, some of
      which have potential implications in airway homeostasis. These include
      vasoregulation, bronchoprotection, anti-inflammatory actions and tissue repair.
      Targeting these effects of CGRP could be a future avenue for modulation of
      certain aspects of airway diseases.

PMID- 15140412
TI  - Shooting for PARs in lung diseases.
AB  - Proteinase-activated receptors (PARs) are novel G-protein-coupled receptors
      activated by serine and other proteinases to induce changes in cellular function.
      There is extensive evidence that PARs are expressed in the airways in a variety
      of cell types that are relevant to inflammatory lung diseases, and that
      activation of these receptors might be linked to significant pathological
      changes. Thus, PARs are exciting new targets in lung disease research. However,
      much of the data to date has come from in vitro studies using limited
      pharmacological tools, and considerably more needs to be known about the
      functions of this family of receptors in the lung before their potential as drug
      targets can be established.

PMID- 15140413
TI  - Bronchial hyperresponsiveness: insights into new signaling molecules.
AB  - Signaling molecules play a critical role in the pathophysiology of airway
      diseases. Recent evidence shows that cyclic ADP-ribose (cADPr), an endogenous
      activator of the ryanodine receptor channel in mammalian cells, modulates agonist
      induced calcium responses in airway smooth muscle (ASM) cells. In addition, cADPr
      mediated calcium release appears to play an important role in the "non-specific"
      increased ASM responsiveness to contractile agonists in cytokine-treated cells, a
      characteristic finding of asthma. Furthermore, other signaling molecules such as
      Rho/Rho kinase and phosphodiesterase also contribute to bronchial
      hyperresponsiveness. Thus, a better understanding of these signaling molecules
      that alter calcium signaling and contractility of ASM might provide new insight
      into novel therapeutic targets for the control of bronchial hyperresponsiveness.

PMID- 15140414
TI  - Direct effects of Th2 cytokines on airway smooth muscle.
AB  - Data summarized in this review indicate that airway smooth muscle cells express
      receptors for cytokines derived from CD4+ T cells and that these cytokines,
      particularly interleukin-13, can act directly on airway smooth muscle cells
      leading to changes in contractile and relaxant responses, proliferation, and the
      ability of smooth muscle cells to generate chemokines such as eotaxin and TARC.
      Moreover, the interleukin-4 receptor-alpha genotype of airway smooth muscle
      appears to be an important determinant of its response to Th2 cytokines.
      Understanding the mechanistic basis for the interactions between these cytokines
      and airway smooth muscle might suggest new avenues for therapeutic intervention
      in asthma.

PMID- 15140415
TI  - Airway mucus hypersecretion in asthma: an undervalued pathology?
AB  - Airway mucus hypersecretion is a feature of many patients with asthma. It is
      indicative of poor asthma control and contributes to morbidity and mortality.
      Excess mucus not only obstructs airways but also contributes to airway
      hyperresponsiveness. Furthermore, asthma might have a specific mucus
      hypersecretory phenotype. Goblet cell hyperplasia and submucosal gland
      hypertrophy are shared with other hypersecretory diseases, such as chronic
      obstructive pulmonary disease; however, some features are different, including
      mucus plugging, mucus "tethering" to goblet cells, plasma exudation, and
      increased amounts of a low charge glycoform of mucin (MUC)5B and the presence of
      MUC2 in secretions. Experimentally, most of the inflammatory mediators and neural
      mechanisms implicated in the pathophysiology of asthma impact upon the mucus
      hypersecretory phenotype. There is currently huge research interest in
      identifying targets involved in inducing mucus abnormalities, which should lead
      to the rational design of anti-hypersecretory drugs for treatment of airway mucus
      hypersecretion in asthma.

PMID- 15140416
TI  - Does aberrant activation of the epithelial-mesenchymal trophic unit play a key
      role in asthma or is it an unimportant sideshow?
AB  - Mechanisms underlying the pathogenesis of asthma remain elusive, although the
      pathological changes observed in human lungs at autopsy are consistent with those
      of a well-defined chronic inflammatory process and are related to disease
      severity. Areas of epithelial metaplasia and damage, and thickening of the sub
      epithelial basal lamina, are common findings. Epithelial cell proliferation is
      accompanied by a concomitant increase in the proliferation of sub-epithelial
      fibroblasts. Each of these processes can be upregulated by cytokines and growth
      factors released from undamaged neighboring cells. However, there is mounting
      evidence to suggest that aberrant repair signals present in chronically inflamed
      airways may influence epithelial cell proliferation and regeneration.
      Furthermore, an aberrant repair process occurring at the mucosal surface might
      trigger a cascade of events deeper within the sub-mucosa, leading to direct
      effects on the number and behaviour of mesenchymal cells, and the resultant
      increased deposition of extracellular matrix that contributes to airway wall
      remodeling. These data have led an increasing number of investigators to ask the
      question whether the epithelial-mesenchymal trophic unit, central to lung
      development, becomes "re-activated" in asthma.

PMID- 15140417
TI  - Steroid resistance in asthma: a major problem requiring novel solutions or a non
      issue?
AB  - Steroid insensitivity in severe asthma is rare but has huge health care costs.
      Thus, 5% of asthmatic patients account for approximately 50% of total health care
      costs. Incorrect diagnosis, non-compliance with therapy and psychological
      problems are all confounding issues, and can account for a failure to respond to
      steroids in many of these patients. A recent report (ENFUMOSA) has suggested that
      severe asthma, of which steroid-resistant asthma is a component, consists of at
      least one, possibly more, distinct disease(s) with differing pathologies. Future
      studies such as Bio-Air and TENOR could confirm this; therefore, it is not
      surprising that well-characterised steroid-resistant and steroid-dependent asthma
      have multiple mechanisms to account for a lack of steroid sensitivity, including
      defective ligand binding to the steroid receptor, abnormal receptor nuclear
      translocation and abnormal association with pro-inflammatory nuclear proteins.
      Distinct treatments might have to be tailored to the individual patient; for
      example, drugs that enhance receptor nuclear translocation will only be effective
      in patients in whom this is a problem. Once issues of diagnosis, compliance and
      psychological disorders have been resolved, true steroid resistance or dependence
      is unlikely to be an issue for most clinicians, who will rarely, if ever, see
      these patients. However, management of those few patients with true steroid
      resistance will require novel therapies tailored to specific subgroups of
      patients.

PMID- 15140418
TI  - COPD: is there light at the end of the tunnel?
AB  - No currently available treatments reduce the progression or suppress the
      inflammation of chronic obstructive pulmonary disease (COPD). However, with a
      better understanding of the inflammatory and destructive process, several targets
      have been identified and new treatments are in clinical development. Several
      specific therapies are directed against the influx of inflammatory cells into the
      airways and lung parenchyma that occurs in COPD, including adhesion molecule and
      chemokine-directed therapy, as well as therapies to inhibit tumour necrosis
      factor-alpha. Several broad-spectrum anti-inflammatory drugs are also in
      development, and include inhibitors of phosphodiesterase-4, p38 mitogen-activated
      protein kinase and nuclear factor-kappaB. There is a need for validated
      biomarkers and monitoring techniques in early clinical studies with new therapies
      for COPD.

PMID- 15140420
TI  - What next for rheumatoid arthritis therapy?
AB  - Introduction of biological agents for the treatment of the chronic inflammatory
      joint disease rheumatoid arthritis has reinvigorated research into this
      debilitating disease. These agents have been shown to both act on the signs and
      symptoms of disease, as well as retard the progression of joint destruction.
      However, these agents are not efficacious in all cases and their expense and
      route of administration can severely limit their use. Therefore the search
      continues not only for additional targets to help those individuals refractive to
      current therapy but also for more affordable orally active small molecule
      alternatives to biological agents.

PMID- 15140421
TI  - The delicate balance between fat and muscle: adipokines in metabolic disease and
      musculoskeletal inflammation.
AB  - Adipose tissue has evolved as a complex organ with functions far beyond the mere
      storage of energy. Chronic oversupply of calories, common to Western-style diets,
      frequently goes hand-in-hand with an altered secretion pattern of adipokines and
      elevated plasma free fatty acid levels, known to modulate insulin sensitivity in
      skeletal muscle. Intramyocellular accumulation of lipids directly attenuates
      insulin signaling within myocytes via distinct kinases. Obesity is also
      accompanied by an enhanced basal inflammatory tone, originating from adipocytes
      and adipose tissue-associated macrophages. In addition, adipocytes accumulate
      within the skeletal muscle and exert direct paracrine effects on muscle insulin
      sensitivity.

PMID- 15140422
TI  - Controlling the balance between osteoblastogenesis and adipogenesis and the
      consequent therapeutic implications.
AB  - The increase in marrow adipogenesis associated with osteoporosis and age-related
      osteopenia is well known clinically. However, we are only now beginning to
      understand the mechanisms that control the differentiation of mesenchymal stem
      cells to either osteoblasts or adipocytes. Recent work with gene silencing and
      overexpression has provided insight into critical pathways that determine the
      fate of these multipotential cells. One of these pathways - that of the nuclear
      hormone receptor peroxisome proliferator activated receptor-gamma - when
      activated, promotes adipogenesis and inhibits osteogenesis. This in vitro
      mechanism of action has been confirmed in vivo using ligands to this receptor.
      Discovery of this and other targets and pathways, such as Wnt signaling,
      notch/delta/jagged ligands and receptors, and RhoA gene expression, provides new
      insights into mesenchymal stem cell differentiation. These pathways provide
      exciting future pharmacological targets with which to enhance bone formation and
      therefore reduce the risk of fracture.

PMID- 15140423
TI  - The complex effects of leptin on bone metabolism through multiple pathways.
AB  - Leptin has recently emerged as a mediator of the protective effects of fat on
      bone tissue. However, it remains difficult to draw a clear picture of how leptin
      effects bone metabolism. From conflicting or apparently contradictory data, it is
      tempting to hypothesize that leptin exerts dual effects depending on bone tissue,
      skeletal maturity and/or signaling pathway. Early in life, leptin might stimulate
      bone growth and bone size through direct angiogenic and chondro-osteogenic
      effects. Later, it may decrease bone remodeling in the mature skeleton, when
      trabecular bone turnover is high, by stimulating the osteoprotegerin-RANK-ligand
      pathway. Leptin also exerts negative effects on bone formation through a
      hypothalamic pathway mediated downstream by the sympathetic nervous system. The
      two pathways could counterbalance each other, with the peripheral and positive
      effects being predominant when leptin central resistance occurs with obesity
      onset.

PMID- 15140424
TI  - The AGE of the matrix: chemistry, consequence and cure.
AB  - Accumulation of advanced glycation endproducts (AGEs) plays a crucial part in the
      development of age-related diseases and diabetic complications. AGEs are formed
      in vivo via the so-called Maillard reaction: a reducing sugar reacts with a
      protein to form a labile Amadori product that is subsequently stabilized,
      producing an irreversible, non-enzymatic post-translational modification of the
      protein involved. Recently, it has become clear that, in addition to sugars,
      lipids play an important role in the initiation of AGE formation, and that
      genetic factors contribute to an individual's AGE levels. The highest AGE levels
      are found in tissues with slow turnover, such as tendon, skin, bone, amyloid
      plaques and cartilage. AGEs exert their effects by adversely affecting the
      mechanical properties of the matrix and by modulating tissue turnover. In
      cartilage, these detrimental effects result in tissue that is more prone to the
      development of osteoarthritis. As such, the accumulation of AGEs provides the
      first molecular mechanism explaining the age-related increase in the incidence of
      osteoarthritis. Ongoing research into anti-AGE-ing therapies, such as
      pyrodoxamine and thiazolium compounds, which are often developed to prevent AGE
      induced diabetic complications, might also prove beneficial for the prevention of
      osteoarthritis.

PMID- 15140425
TI  - Emerging therapeutic targets in psoriasis.
AB  - Biopharmaceuticals that target specific disease-mediating molecules have advanced
      our understanding of the pathogenesis of psoriasis. The traditional paradigm that
      psoriasis is primarily a disease of epidermal cells has been replaced with a
      model that now includes keratinocyte-derived factors, inflammatory mediators and
      angiogenic mechanisms. Recent studies have highlighted some of the key molecules
      involved in all of these pathogenic processes. Several have already been
      evaluated as putative targets in in vitro and in vivo studies, whereas other
      molecules are significantly upregulated in psoriasis and require further study to
      elucidate their role and contribution to disease. Although not all these
      molecules will eventually qualify as drug targets, data from similar experimental
      strategies are predicted to underpin the next generation of candidate targets and
      novel therapeutic approaches.

PMID- 15140426
TI  - 2D solid state NMR spectral simulation of 3(10), alpha, and pi-helices.
AB  - Transmembrane helices are more uniform in structure than similar helices in water
      soluble proteins. Solid state NMR of aligned bilayer samples is being
      increasingly used to characterize helical membrane protein structures.
      Traditional spectroscopic methods have difficulty distinguishing between helices
      with i to i + 3 (3(10)), i to i + 4 (alpha), and i to i + 5 (pi) hydrogen bonding
      topology. Here, we show that resonance patterns in PISEMA spectra simulated for
      these different helices show unique and striking features. The size and shape of
      these Polar Index Slant Angle (PISA) wheels, as well as the resonances per turn
      and clockwise versus counter-clockwise sequential connectivity of the resonances
      demonstrate how these different helical structures, if present as a uniform
      structure, will be readily distinguished, and characterized.

PMID- 15140427
TI  - Measurements of motionally averaged heteronuclear dipolar couplings in MAS NMR
      using R-type recoupling.
AB  - A novel MAS NMR approach is presented for the determination of heteronuclear
      dipolar couplings in unoriented materials. The technique is based on the proton
      detected local field (PDLF) protocol, and achieves dipolar recoupling by R-type
      radio-frequency irradiation. The experiment, which is called R-PDLF spectroscopy,
      is demonstrated on solid and liquid-crystalline systems. For mobile systems, it
      is shown that the R-PDLF scheme provides better dipolar resolution as compared to
      techniques combining conventional separated local field (SLF) spectroscopy with R
      type recoupling.

PMID- 15140428
TI  - Variable temperature system using vortex tube cooling and fiber optic temperature
      measurement for low temperature magic angle spinning NMR.
AB  - We describe the construction and operation of a variable temperature (VT) system
      for a high field fast magic angle spinning (MAS) probe. The probe is used in NMR
      investigations of biological macromolecules, where stable setting and continuous
      measurement of the temperature over periods of several days are required in order
      to prevent sample overheating and degradation. The VT system described is used at
      and below room temperature. A vortex tube is used to provide cooling in the
      temperature range of -20 to 20 degrees C, while a liquid nitrogen-cooled heat
      exchanger is used below -20 degrees C. Using this arrangement, the lowest
      temperature that is practically achievable is -140 degrees C. Measurement of the
      air temperature near the spinning rotor is accomplished using a fiber optic
      thermometer that utilizes the temperature dependence of the absorption edge of
      GaAs. The absorption edge of GaAs also has a magnetic field dependence that we
      have measured and corrected for. This dependence was calibrated at several field
      strengths using the well-known temperature dependence of the (1)H chemical shift
      difference of the protons in methanol.

PMID- 15140430
TI  - Linear phase correction of folded multidimensional NMR data by zero inter
      filling.
AB  - We describe a procedure to enable linear phase correction of extensively folded
      multidimensional NMR data. This involves adding zeros in between data points in
      the indirect dimension to increase the effective bandwidth in the associated
      spectral window. A standard linear phase correction can then be applied to the
      data and a properly phased spectrum obtained after additional shuffling of the
      data in many instances.

PMID- 15140429
TI  - Spin state selectivity and heteronuclear Hartmann-Hahn transfer.
AB  - Spin state selectivity can be obtained if inphase and antiphase magnetization can
      be transformed into each other. Heteronuclear Hartmann-Hahn transfer is usually
      used for the transfer of inphase magnetization. For a two spin system, however, a
      building block can be constructed that transfers inphase into antiphase
      magnetization and vice versa. The article gives a detailed description of the
      building block as well as experiments with elements similar to spin state
      selective coherence transfer (S(3)CT) and spin state selective excitation
      (S(3)E). The possibility of 'sensitivity enhancement' is pointed out and an
      application in the double selective measurement of coupling constants using a
      combination of CW-cross-polarization and the S(3)CT-type approach is
      demonstrated.

PMID- 15140431
TI  - Fast EPR imaging at 300 MHz using spinning magnetic field gradients.
AB  - Electron paramagnetic resonance imaging (EPRI) technology has rapidly progressed
      in the last decade enabling many important applications in the fields of biology
      and medicine. At frequencies of 300-1200 MHz a range of in vivo applications have
      been performed. However, the requisite imaging time duration to acquire a given
      number of projections, limits the use of this technique in many in vivo
      applications where relatively rapid kinetics occur. Therefore, there has been a
      great need to develop approaches to accelerate EPRI data acquisition. We report
      the development of a fast low-frequency EPRI technique using spinning magnetic
      field gradients (SMFG). Utilizing a 300 MHz CW (continuous wave) EPRI system,
      SMFG enabled over 10-fold accelerated acquisition of image projections. 2D images
      with over 200 projections could be acquired in less than 3s and with 20s
      acquisitions good image quality was obtained on large aqueous free radical
      samples. This technique should be particularly useful for in vivo studies of free
      radicals and their metabolism.

PMID- 15140432
TI  - Investigating fatty acids inserted into magnetically aligned phospholipid
      bilayers using EPR and solid-state NMR spectroscopy.
AB  - This is the first time (2)H solid-state NMR spectroscopy and spin-labeled EPR
      spectroscopy have been utilized to probe the structural orientation and dynamics
      of a stearic acid incorporated into magnetically aligned phospholipid bilayers or
      bicelles. The data gleaned from the two different techniques provide a more
      complete description of the bilayer membrane system. Both methods provided
      similar qualitative information on the phospholipid bilayer, high order, and low
      motion for the hydrocarbon segment close to the carboxyl groups of the stearic
      acid and less order and more rapid motion at the end towards the terminal methyl
      groups. However, the segmental order parameters differed markedly due to the
      different orientations that the nitroxide and C-D bond axes transform with the
      various stearic acid acyl chain conformations, and because of the difference in
      dynamic sensitivity between NMR and EPR over the timescales examined. 5-, 7-, 12
      , and 16-doxylstearic acids spin-labels were used in the EPR experiments and
      stearic acid-d(35) was used in the solid-state NMR experiments. The influence of
      the addition of cholesterol and the variation of temperature on the fatty acid
      hydrocarbon chain ordering in the DMPC/DHPC phospholipid bilayers was also
      studied. Cholesterol increased the degree of ordering of the hydrocarbon chains.
      Conversely, as the temperature of the magnetically aligned phospholipid bilayers
      increased, the order parameters decreased due to the higher random motion of the
      acyl chain of the stearic acid. The results indicate that magnetically aligned
      phospholipid bilayers are an excellent model membrane system and can be used for
      both NMR and EPR studies.

PMID- 15140433
TI  - Clean TOCSY transfer through residual dipolar couplings.
AB  - The transfer efficiency of cross-relaxation compensated (Clean) TOCSY sequences
      is analyzed for applications to residual dipolar couplings. Surprisingly most
      conventional Clean TOCSY sequences are very inefficient for dipolar transfer. It
      is shown theoretically, that this is a general property of all phase-alternating
      mixing sequences, i.e., for such sequences the suppression of cross-relaxation
      excludes dipolar transfer in the spin-diffusion limit. A new family of clean
      dipolar TOCSY sequences is derived which provides excellent transfer efficiencies
      for a broad range of offset frequencies.

PMID- 15140434
TI  - Magnetic material arrangement in oriented termites: a magnetic resonance study.
AB  - Temperature dependence of the magnetic resonance is used to study the magnetic
      material in oriented Neocapritermes opacus (N.o.) termite, the only prey of the
      migratory ant Pachycondyla marginata (P.m.). A broad line in the g = 2 region,
      associated to isolated nanoparticles shows that at least 97% of the magnetic
      material is in the termite's body (abdomen + thorax). From the temperature
      dependence of the resonant field and from the spectral linewidths, we estimate
      the existence of magnetic nanoparticles 18.5+/-0.3 nm in diameter and an
      effective magnetic anisotropy constant, K(eff) between 2.1 and 3.2 x
      10(4)erg/cm(3). A sudden change in the double integrated spectra at about 100K
      for N.o. with the long body axis oriented perpendicular to the magnetic field can
      be attributed to the Verwey transition, and suggests an organized film-like
      particle system.

PMID- 15140435
TI  - Nonequivalent spectra of unpaired electrons in field and frequency modulation.
AB  - We report a difference in the spectral lineshapes of continuous-wave (CW)
      electron paramagnetic resonance (EPR) spectroscopy between field and frequency
      modulation. This finding addresses the long-standing question of the effect of
      modulation in EPR absorption. We compared the first-derivative EPR spectra at 1.1
      GHz for lithium phthalocyanine crystals, which have a single narrow linewidth in
      the EPR absorption spectrum, using field and frequency modulation. The
      experimental findings suggest that unpaired electrons have different behaviors
      under perturbation due to field and frequency modulation.

PMID- 15140436
TI  - Parametric methods for frequency-selective MR spectroscopy-a review.
AB  - Accurate quantitation of the spectral components in a pre-selected frequency band
      for magnetic resonance spectroscopy (MRS) signals is a frequently addressed
      problem in the MR community. One obvious application for such a frequency
      selective technique is to lower the computational burden in situations when the
      measured data sequence contains too many samples to be processed using a standard
      full-spectrum method. Among the frequency-selective methods previously proposed
      in the literature, only a few possess the two features of primary concern: high
      robustness against interferences from out-of-band components and low
      computational complexity. In this survey paper we consider five spectral analysis
      methods which can be used for MRS signal parameter estimation in a selected
      frequency band. We re-derive the filter diagonalization method (FDM) in a new way
      that allows an easy comparison to the other methods presented. Then we introduce
      a frequency-selective version of the method of direction estimation (MODE) which
      has not been applied to MR-spectroscopy before. In addition, we present a
      filtering and decimation technique using a maximum phase bandpass FIR-filter and
      relate it to a similar ARMA-modeling approach known as SB-HOYWSVD (sub-band high
      order Yule-Walker singular value decomposition). Finally, we study the numerical
      performances of these four methods and compare them to that of the recently
      introduced SELF-SVD (Singular Value Decomposition-based method usable in a
      SELected Frequency band) in several examples using simulated MR data, and discuss
      the benefits and disadvantages of each technique.

PMID- 15140437
TI  - Application of trilinear SLICING to analyse a single relaxation curve.
AB  - Determining the time constants and amplitudes of exponential decays from
      relaxation data is a common task in LF-NMR. In this communication, we present an
      application of the SLICING algorithm to evaluate its possibilities for solving
      this problem. The method, originally introduced to compare different samples, is
      applied here to analyse a single relaxation curve, using the embedding technique.
      To test this procedure, we acquired data sets from samples of liquids properly
      separated, and characterized by different relaxation times. The results show a
      good estimation of parameters, comparable with those obtained applying
      Marquardt's algorithm, when the components have sufficiently different relaxation
      times.

PMID- 15140439
TI  - On the analysis of broad Dysonian electron paramagnetic resonance spectra.
AB  - We analyze the equation used for simulating the lineshapes of broad electron
      paramagnetic resonance spectra in conducting samples (i.e., broad Dysonian
      lineshapes) where it becomes necessary to include the effects of both clockwise
      and counterclockwise rotating components of the microwave magnetic field. Using
      symmetry arguments, we propose a modification to the equation. We show that the
      modified equation fits the experimental results better than the equation used in
      literature.

PMID- 15140438
TI  - Fitting of the beat pattern observed in NMR free-induction decay signals of
      concentrated carbohydrate-water solutions.
AB  - A series of mathematical functions has been used to fit the proton free-induction
      decays (FIDs) of concentrated carbohydrate-water samples. For the solid protons,
      these functions included a sinc function, as well as the Fourier transforms of
      single and multiple Pake functions multiplied by a Gaussian broadening. The NMR
      signal from the mobile protons is described by an exponential function. It is
      found that in most cases the sinc function gives a satisfactory result and
      provides valuable information about the second moment M(2) and the ratio of solid
      to mobile protons (f(s) / f(m)). A good indication for using the sinc function is
      the presence of a beat in the FID. For high temperatures this approach breaks
      down, and a biexponential fit is more appropriate. If a clear dipolar splitting
      is observable in the NMR spectra, the Pake function (or a multiple Pake fit)
      should be used. In this case information about M(2) and f(s) / f(m) can also be
      obtained.

PMID- 15140440
TI  - Wavelet-based ultra-high compression of multidimensional NMR data sets.
AB  - The application of a lossy data compression algorithm based on wavelet transform
      to 2D NMR spectra is presented. We show that this algorithm affords rapid and
      extreme compression ratios (e.g., 800:1), providing high quality reconstructed 2D
      spectra. The algorithm was evaluated to ensure that qualitative and quantitative
      information are retained in the compressed NMR spectra. Whilst the maximum
      compression ratio that can be achieved depends on the number of signals and on
      the difference between the most and the least intense peaks (dynamic range), a
      compression ratio of 80:1 is affordable even for the challenging case of
      homonuclear 2D experiments of large biomolecules.

PMID- 15140441
TI  - A new sensitive isotropic-anisotropic separation experiment-SPEED MAS.
AB  - A new sensitive 2D isotropic-anisotropic separation experiment that utilizes
      stroboscopic phase encoding in the evolution dimension (SPEED) under magic angle
      sample spinning is presented. This 2D experiment consists of a train of 2N - 1 pi
      pulses that are applied over 2N rotor periods. The pi pulse train effectively
      reduces the apparent spinning speed in the evolution dimension by a factor of 1 /
      (2N) from the mechanical spinning speed. Thus, problems commonly associated with
      magic angle turning such as stable slow spinning, different matching and TPPM
      proton decoupling conditions are avoided. Data replication similar to the five pi
      replicated magic angle turning (FIREMAT) and pseudo 2D sideband suppression
      (P2DSS) experiments transfers resolution from the acquisition dimension to the
      evolution dimension. Hence, large spectral windows with good digital resolution
      are obtained with a few evolution increments. Here, slow spinning sideband
      patterns are extracted from the replicated 2D dataset with TIGER processing.
      Nevertheless, 2D Fourier transformation is also applicable. The extracted
      sideband patterns are identical to magic angle turning sideband pattern allowing
      for easy extraction of principal shift components. Accurate (13)C principal shift
      components are obtained for 3-methylglutaric acid using SPEED and FIREMAT
      experiments to validate the method. Furthermore, SPEED spectra for calcium
      acetate and alpha santonin are reported to show the wide applicability of this
      new experiment.

PMID- 15140442
TI  - Measurement of one-bond heteronuclear dipolar coupling contributions for amine
      and diastereotopic methylene protons.
AB  - One-bond heteronuclear and two-bond homonuclear residual dipolar couplings
      measured at methylene or amine sites can be utilized as long-range constraints in
      structure determination of molecules as well as to facilitate characterization of
      local conformation by stereospecific assignment of diastereotopic protons. We
      present two J-modulated HMQC type experiments to measure the one-bond
      heteronuclear dipolar coupling contributions of geminal protons individually. In
      addition two-bond homonuclear residual dipolar couplings between the
      diastereotopic protons are also obtained.

PMID- 15140443
TI  - Rotational-resonance distance measurements in multi-spin systems.
AB  - It is demonstrated that internuclear distances can be evaluated from rotational
      resonance (RR) experiments in uniformly (13)C-labelled compounds. The errors in
      the obtained distances are less than 10% without the need to know any parameters
      of the spin system except the isotropic chemical shifts of all spins. We describe
      the multi-spin system with a simple fictitious spin-1/2 model. The influence of
      the couplings to the passive spins (J and dipolar coupling) is described by an
      empirical constant offset from the rotational-resonance condition. Using
      simulated data for a three-spin system, we show that the two-spin model describes
      the rotational-resonance transfer curves well as long as none of the passive
      spins is close to a rotational-resonance condition with one of the active spins.
      The usability of the two-spin model is demonstrated experimentally using a sample
      of acetylcholine perchlorate with labelling schemes of various levels of
      complexity. Doubly-, triply-, and fully labelled compounds lead to strongly
      varying RR polarization-transfer curves but the evaluated distances using the two
      spin model are identical within the expected error limits and coincide with the
      distance from the X-ray structure. Rotational-resonance distance measurements in
      fully labelled compounds allow, in particular, the measurement of weak couplings
      in the presence of strong couplings.

PMID- 15140444
TI  - Uniform-sign cross-peak double-quantum-filtered correlation spectroscopy.
AB  - We detail the uniform-sign cross-peak double-quantum-filtered correlation
      spectroscopy (UC2QF COSY) experiment, a new through-bond correlation method for
      disordered solids. This experiment is a refocused version of the popular double
      quantum-filtered correlation spectroscopy experiment in liquids. Its key feature
      is that it provides in-phase and doubly absorptive line shapes, which renders it
      robust for chemical shift correlation in solids. Both theory and experiment point
      to distinct advantages of this protocol, which are illustrated by several
      experiments under challenging conditions, including fast magic-angle spinning
      (30kHz), anisotropic molecular motion, and (13)C correlation spectroscopy at the
      natural abundance isotope level.

PMID- 15140445
TI  - Efficient and accurate determination of the overall rotational diffusion tensor
      of a molecule from (15)N relaxation data using computer program ROTDIF.
AB  - We present a computer program ROTDIF for efficient determination of a complete
      rotational diffusion tensor of a molecule from NMR relaxation data. The
      derivation of the rotational diffusion tensor in the case of a fully anisotropic
      model is based on a six-dimensional search, which could be very time consuming,
      particularly if a grid search in the Euler angle space is involved. Here, we use
      an efficient Levenberg-Marquardt algorithm combined with Monte Carlo generation
      of initial guesses. The result is a dramatic, up to 50-fold improvement in the
      computational efficiency over the previous approaches. This method is
      demonstrated on a computer-generated and real protein systems. We also address
      the issue of sensitivity of the diffusion tensor determination from (15)N
      relaxation measurements to experimental errors in the relaxation rates and
      discuss possible artifacts from applying higher-symmetry tensor model and how to
      recognize them.

PMID- 15140446
TI  - Enhancing MQMAS sensitivity using signals from multiple coherence transfer
      pathways.
AB  - Multiple-quantum magic-angle spinning experiment removes second-order quadrupolar
      broadening from the central-transition of half-integer quadrupolar nuclei. This
      paper presents a novel scheme to enhance the sensitivity of MQMAS using signals
      from multiple coherence transfer pathways. The enhancement can be obtained in two
      ways. The first method uses the multiplex phase cycling to acquire MQMAS spectra
      from various coherence transfer pathways simultaneously. An addition of spectra
      collected with no extra time enhances the efficiency of the experiment. The
      second method, soft-pulse-added-mixing, is designed based on a complete alias of
      coherence transfer pathways. By properly fixing the soft-pulse phase, signals
      from various coherence transfer pathways can add constructively resulting higher
      signal intensities. The two methods are demonstrated for sensitivity enhancement
      with samples of spin-3/2 and 5/2.

PMID- 15140447
TI  - A suite of 3D NMR methods for characterizing complex hydrocarbon structure
      fragments.
AB  - A suite of triple resonance 3D NMR experiments is presented for the complete
      connectivity assignment of the hydrocarbon network in complex macromolecular and
      supramolecular organic structures. These new 3D NMR methods rely only on the
      presence of a unique set of (13)C resonances (from (13)C(X)) which are separated
      from the rest of the (13)C NMR spectrum. These experiments take the advantage of
      region selective excitation and selective inversion by composite pulses to
      provide correlations among H(A), (13)C(A); H(B), (13)C(B) and neighboring
      (13)C(X) resonances along three frequency dimensions. These methods include:
      gHC(A)C(X), gHC(A)C(X)-HH-TOCSY and gHC(A)C(X)-CC-TOCSY experiments. The utility
      of this approach is illustrated with spectra of selected structure fragments in
      poly(ethylene-co-n-butyl acrylate-co-carbon monoxide) (polyEBC) prepared from
      1,2,3-(13)C(3)-n-butyl acrylate.

PMID- 15140448
TI  - Compensation for pulse imperfections in rotational-echo double-resonance NMR by
      composite pulses and EXORCYCLE.
AB  - We describe a simple method to compensate for pulse-angle errors in rotational
      echo double resonance (REDOR) experiments for determining heteronuclear distances
      in solids. By using composite 180 degrees pulses on the unobserved dephasing spin
      and EXORCYCLE for the single pi pulse on the observed channel, the REDOR curve
      becomes much less sensitive to pulse-angle errors. Both improvements are
      demonstrated by experiments on the model compound, (15)N, (13)Calpha -labeled N-t
      BOC-glycine, and are confirmed by numerical simulations. The advantage of
      EXORCYCLE is also shown analytically using the product operator formalism. The
      proposed simple schemes compensate for unavoidable pulse-angle errors that arise,
      for example, from radiofrequency field inhomogeneity. They also make REDOR
      experiments more accurate and robust for low-sensitivity samples where direct
      pulse-length calibration is difficult.

PMID- 15140449
TI  - Decisions on women's health: menopause and hormone replacement therapy.

PMID- 15140450
TI  - Women's views of optimal risk communication and decision making in general
      practice consultations about the menopause and hormone replacement therapy.
AB  - Primary care consultations about the menopause and hormone replacement therapy
      (HRT) involve decision making in the face of clinical uncertainty. This
      qualitative study used focus groups and semi-structured interviews with primary
      care patients to explore patients' perspectives of optimal risk communication and
      decision making, and their views on how to improve its effectiveness. The study
      was set in two general practices in Cambridge, and the participants were 40 women
      aged between 50 and 55 years, known to be Current-Users (CU), Ex-Users (EU), or
      Never-Users (NU) of HRT. The majority of participants favoured communication of
      risks and benefits to facilitate an informed and personalised choice resulting in
      informed shared decision making, while some wanted a more directive approach.
      Women felt that risk communication would be optimised by the provision of
      unbiased, truthful and summarised information, and also by the personalisation of
      both this risk information and subsequent management of the menopause and
      treatment with HRT. Barriers to optimal risk communication and decision making
      included lack of time, GP attitudes and poor communication in the primary care
      consultation. In summary, consultations concerning the menopause and HRT involve
      complex decision making in the face of uncertainty, and most patients favour
      evidence-based, individualised risk information and shared decision making
      leading to informed choices. Some patients wish for a more directive approach,
      and practitioners need to develop skills to evaluate each patient's needs at each
      consultation.

PMID- 15140451
TI  - Over the counter medicines and the need for immediate action: a further
      evaluation of European Commission recommended wordings for communicating risk.
AB  - A study examined people's interpretation of European Commission (EC) recommended
      verbal descriptors for risk of medicine side effects, and actions to take if they
      do occur. Members of the general public were presented with a fictitious (but
      realistic) scenario about suffering from a stiff neck, visiting the local
      pharmacy and purchasing an over the counter (OTC) medicine (Ibruprofen). The
      medicine came with an information leaflet which included information about the
      medicine's side effects, their risk of occurrence, and recommended actions to
      take if adverse effects are experienced. Probability of occurrence was presented
      numerically (6%) or verbally, using the recommended EC descriptor (common).
      Results showed that, in line with findings of our earlier work with prescribed
      medicines, participants significantly overestimated side effect risk.
      Furthermore, the differences in interpretation were reflected in their judgements
      of satisfaction, side effect severity, risk to health, and intention to take the
      medicine. Finally, we observed no significant difference between people's
      interpretation of the recommended action descriptors ('immediately' and 'as soon
      as possible').

PMID- 15140452
TI  - On the enhancement of efficiency in care for cancer patients in outpatient
      clinics: an instrument to accelerate psychosocial screening and referral.
AB  - Many cancer patients experience psychosocial problems that go unnoticed by
      caregivers. To improve this situation, an instrument has been developed and
      tested to identify such problems. This instrument, the integral checklist, was
      put to the test in two outpatient departments of different hospitals with an
      intervention and a control group (105 and 124 patients, respectively). To
      evaluate the efficiency of the checklist, both groups had to complete a
      questionnaire after consultation. Results showed that the checklist assisted
      specialists to be more often pro-active in discussing psychosocial problems with
      their patients, and more patients with psychosocial problems were referred. Most
      of the patients appreciated going through the checklist with their specialist.
      The checklist proves to fit in well with hospital routines and using it costs the
      specialist no extra time. It appears to be an instrument which improves
      efficiency of consultation. Moreover, the checklist is turned out to be useful as
      a management tool to divert patients' attention away from the waiting time.

PMID- 15140453
TI  - The use and acceptability of a one-on-one peer support program for Australian
      women with early breast cancer.
AB  - A population-based survey of Australian women diagnosed with early breast cancer
      examined the uptake and acceptability of a peer support program, the Breast
      Cancer Support Service (BCSS). We examined the characteristics and perceptions of
      women who did and did not use the BCSS. More than one-third (36%) had used the
      BCSS, most of whom first heard of it from hospital staff (36%) or clinicians
      (16%). Women perceived meeting someone else with similar experiences (53%) as the
      most beneficial aspect of the program and 89% said they would definitely
      recommend it to others. The findings suggest that uptake is related to provision
      of information about the BCSS. Peer support programs appear to be acceptable to
      both women who do and do not use the BCSS. To ensure that women can choose
      whether to participate in peer support programs requires strategies that
      encourage health professionals to provide comprehensive supportive care
      information.

PMID- 15140454
TI  - Motivational interviewing in health settings: a review.
AB  - There is evidence that patient-centred approaches to health care consultations
      may have better outcomes than traditional advice giving, especially when
      lifestyle change is involved. Motivational interviewing (MI) is a patient-centred
      approach that is gathering increased interest in health settings. It provides a
      way of working with patients who may not seem ready to make the behaviour changes
      that are considered necessary by the health practitioner. The current paper
      provides an overview of MI, with particular reference to its application to
      health problems.

PMID- 15140455
TI  - The effects of AIDS prevention programs by lay health advisors for migrants in
      The Netherlands.
AB  - Two studies describe the effectiveness of acquired immunodeficiency syndrome
      (AIDS) prevention programs by lay health advisors (LHAs) for migrants in The
      Netherlands. The effects of such AIDS programs were evaluated (Study 1) and
      compared with the effects of professional health advisors (PHAs, i.e. medical
      doctors or nurses) (Study 2). The first study concerned Turkish and Moroccan
      migrants and showed positive effects on knowledge, behavioral control, and social
      norm towards condom use. Iraqi refugees participated in the second study that
      concerned a direct comparison of LHA- and PHA-based programs. Both programs
      result in positive effects in terms of attitude change and knowledge, but the LHA
      program resulted in a stronger intention to discuss AIDS with children. Analyses
      predicting intention to use condoms provide evidence that LHA programs lead to a
      stronger relation between attitudes and intention. This suggests that LHA-based
      AIDS programs are more successful in inducing internally motivated intentions to
      safe sex practices, such as condom use.

PMID- 15140456
TI  - We are the experts: people with asthma talk about their medicine information
      needs.
AB  - People with chronic illness are being encouraged to become more involved in their
      care. For this, they need to be well informed about their medicines, and more
      written medicines information is becoming available. However, there is little
      data about its effectiveness and impact. This study examined the patient
      perspective of medicines information through focus groups of people with asthma.
      Most participants actively sought medicines information from a variety of
      professional and lay sources. There were some positive experiences but many
      examples of partial or total information failure. Individualised information was
      valued and medicine leaflets were generally seen as less helpful than face-to
      face advice. Some felt strongly that patients with long experience should be
      involved in the development of medicine information leaflets. We conclude that
      medicine information leaflets do not currently meet the needs of users and that
      people who take medicines should be involved in their development and testing.

PMID- 15140457
TI  - Setting up a health education website: practical advice for health professionals.
AB  - Recently, both popular and professional publications about health care have begun
      to express enthusiasm for the Internet as a source of medical information and
      possibly of psychological support for those with serious illnesses. However,
      there are pitfalls for practitioners and researchers who seek to capitalise on
      these patient education possibilities. We describe here the process and mixed
      outcomes of the efforts of a multidisciplinary team to set up and evaluate a
      website for rural women with breast cancer. We provide recommendations for other
      health professionals contemplating similar ventures, and also identify some
      future steps to develop and research this potentially valuable form of patient
      education and support.

PMID- 15140458
TI  - GPs' views on involvement of older patients: an European qualitative study.
AB  - Involvement of older patients in general practice care is regarded as important,
      but is not widespread. To determine specific barriers to the involvement of older
      patients in general practice care and to identify variations between countries,
      we performed an international comparative study based on qualitative interviews
      with 233 general practitioners (GPs) in 11 countries. Most GPs thought that
      involving older patients had positive outcomes. GPs saw patient involvement as a
      process taking place solely during consultations. The main barrier for GPs was
      lack of time. Barriers related to older patients were their feelings of respect
      for doctors, their lack of experience in being involved and possible mental and
      physical impairments. To conclude, increasing involvement of older patients is
      not easy and will only be effective when GPs have adopted a more developed
      concept of patient involvement and are supported with the different methods for
      achieving this. The range of appropriate interventions may be similar in all
      countries.

PMID- 15140459
TI  - Haemodialysis patients' beliefs about renal failure and its treatment.
AB  - Patients' beliefs about illness are important because they influence adherence
      and adjustment, but they are often surprising and idiosyncratic. Qualitative
      research can identify them in ways that are not shaped by psychological theory,
      but quantification is necessary if clinicians are to be informed about the
      beliefs that are likely to be prevalent in their patients. Qualitative analysis
      of interviews with 16 haemodialysis (HD) patients identified beliefs about end
      stage renal failure (ESRF) and its treatment that were formed into a
      questionnaire, completed by 156 similar patients. Patients attributed ESRF to
      diverse factors including lack of self-care and inadequate medical care. Patients
      lacked a clear belief in the mechanism of action of dietary control, and its
      necessity was not readily acknowledged. The common view of haemodialysis as
      'cleansing' extended to the reassuring belief that it would purge the body of
      disallowed food or drink. Many patients regarded haemodialysis and dietary
      control as externally imposed challenges that dominated life. The findings
      identify potential targets for educational intervention to improve adherence and
      adjustment and predictions about effects of patients' beliefs that can be tested
      in future prospective studies.

PMID- 15140460
TI  - Decision analysis for newly diagnosed hypertensive patients: a qualitative
      investigation.
AB  - This study adopted a qualitative approach to explore patients' views on the
      usefulness of a decision analytic decision aid (DA). Semi-structured interviews
      were conducted with 15 newly diagnosed hypertensive patients who had been
      recruited for a factorial randomised controlled trial of two decision aids.
      Issues investigated included respondents' attitudes to information, their views
      on the nature of their relationship with their general practitioner (GP)
      (paternalistic, shared or consumerist), the ease of use and potential wider
      application of the computerised decision aid and its influence upon their
      decision-making about whether or not to begin anti-hypertensive treatment. Views
      on the decision aid were favourable. For the majority, the decision aid appeared
      to confirm and/or clarify their stated preferences towards medicine-taking.
      Occasionally it could provoke a major shift in a respondent's attitude to
      medicine-taking, while in a few it had no discernible effect. While views on the
      decision aid were favourable, it was difficult to determine whether this was due
      to the individualised cardiovascular risk information it provided or the decision
      analytic process itself.

PMID- 15140461
TI  - The effect of format modifications and reading comprehension on recall of
      informed consent information by low-income parents: a comparison of print, video,
      and computer-based presentations.
AB  - A randomized trial comparing the amount of knowledge orally recalled from four
      different presentations of the same consent information was conducted in a non
      clinic sample of 233 low-income parents who displayed a range of reading
      comprehension skill. The study simulated recruitment of children into one of two
      actual studies underway at another location: one involved high risk to
      participants, the other did not. Use of a non-clinic sample controlled for prior
      knowledge of the conditions, and avoiding discussion of the information further
      assured that differences in recalled information could be attributed more
      confidently to the format itself. The formats included the original written
      forms, enhanced print (simpler language, topic headings, pictures), narrated
      videotapes, and self-paced PowerPoint presentations via laptop computer with
      bulleted print information, pictures, and narration. No format-related
      differences in recalled information were found in the full sample but for the 124
      individuals with reading comprehension scores at or below the 8th grade level,
      the enhanced print version tended to be more effective than either the original
      form or the video. Across all formats, more information was recalled about the
      low-risk study. The findings emphasize the necessity for clinicians and
      researchers to verify understanding of consent information, especially when there
      is risk of reduced literacy skill. Reliance on video to convey information in
      preference to well-done print media appeared questionable.

PMID- 15140462
TI  - Development and process evaluation of a web-based smoking cessation program for
      college smokers: innovative tool for education.
AB  - Smoking cessation interventions are needed for young adults. Innovative
      approaches to behavior change for this population should be tested. Formative
      research and process evaluation of those approaches would result in more
      effective programs. This paper presents the development process and process
      evaluation of a web-based smoking cessation program. A description of the stages
      of development is presented with formative research, development of the web-based
      intervention, formative evaluation, and process evaluation. The smokers reported
      high usage of the intervention and satisfaction with the intervention in that it
      helped to raise their consciousness about quitting, encouraged them to set
      behavioral goals, provided stages of change feedback, and offered interactivity
      in presenting information and strategies about quitting. The Internet may be a
      promising tool for patient education according to the process results.

PMID- 15140463
TI  - A randomized controlled trial of a nurse-administered educational intervention
      for improving cancer pain management in ambulatory settings.
AB  - The persistence of negative attitudes towards cancer pain and its treatment
      suggests there is scope for identifying more effective pain education strategies.
      This randomized controlled trial involving 189 ambulatory cancer patients
      evaluated an educational intervention that aimed to optimize patients' ability to
      manage pain. One week post-intervention, patients receiving the pain management
      intervention (PMI) had a significantly greater increase in self-reported pain
      knowledge, perceived control over pain, and number of pain treatments
      recommended. Intervention group patients also demonstrated a greater reduction in
      willingness to tolerate pain, concerns about addiction and side effects, being a
      "good" patient, and tolerance to pain relieving medication. The results suggest
      that targeted educational interventions that utilize individualized instructional
      techniques may alter cancer patient attitudes, which can potentially act as
      barriers to effective pain management.

PMID- 15140464
TI  - The biopsychosocial model in medical research: the evolution of the health
      concept over the last two decades.
AB  - The object of this study was to assess the change towards a biopsychosocial
      health concept among medical researchers in the last two decades, after the
      explicit criticism of the biomedical model in the late 1970s because of its
      somatic reductionism. The concepts of 'health' or 'healthy status of an
      individual' as reported as variable in empirical articles published in the
      journal The Lancet over the years 1978-1982 (period a) and 1996-2000 (period b)
      were searched by means of Medline and compared for their definition of these
      variables. None of the 52 examined papers set out a positive and replicable
      definition of 'health' (seven papers) or 'healthy status' (45). No difference was
      found between the two periods studied except for the failure of reports to
      describe 'healthy status' at all (65.5% in a, 19% in b). Most articles do it in
      an indirect way, namely through exclusion conditions of subjects taking part in
      treatment or control groups. Only three studies include psychological dimensions
      in their measures of 'healthy status' (two in a, one in b). Concerning 'health',
      all seven examined papers include psychological or both psychological and social
      dimensions. Although a change towards a more holistic concept of health has
      occurred in academic and institutional contexts over the last few decades, there
      does not appear to have been a parallel change in the practical domains of
      medicine. Possible reasons are discussed, specially the difficulty of applying
      the biopsychosocial model in medical care and the difficulty of competing with
      the traditional biomedical concept of health, which has proved fruitful and
      dominant in medicine over the past three centuries.

PMID- 15140465
TI  - Differences in the regulation of BDNF and NGF synthesis in cultured neonatal rat
      astrocytes.
AB  - Using a new brain-derived neurotrophic factor (BDNF) specific enzyme-immunoassay,
      we determined the basal cellular content of BDNF protein in neonatal rat
      astrocytes in primary culture, thus confirming the ability of astrocytes to
      synthesize BDNF in addition to nerve growth factor (NGF). We subsequently
      monitored the influence of different pharmacological agents: neurotransmitter
      receptor agonists, cytokines, and second messenger up-regulators, on the
      synthesis of BDNF and NGF. Marked differences in the regulation of their
      synthesis by the above pharmacological agents were observed in our study. The
      basal cellular levels of BDNF protein in cultured neonatal rat cortical and
      cerebellar astrocytes were 15.9 +/- 0.3 and 18.7 +/- 0.4 pg BDNF/mg cell protein,
      respectively, and differ significantly between astrocytes from different brain
      regions, whereas NGF levels were the same (16.1 +/- 0.3 and 16.2 +/- 0.7 pg
      NGF/mg cell protein, respectively). Screening different neurotransmitter systems
      for their influence on BDNF and NGF synthesis in cortical astrocytes revealed
      that dopamine (0.15 mM) is a potent up-regulator of BDNF protein synthesis in
      astrocytes, while kainic acid (50 microM) and histamine (1 microM) did not raise
      the cellular level of BDNF protein. Dopamine had no influence on NGF synthesis,
      while kainic acid caused minor, and histamine marked, elevation of NGF cellular
      content. Tumor necrosis factor-alpha (30 ng/ml) and interleukin-1beta (10 U/ml)
      treatments did not influence BDNF synthesis, whereas they markedly increased NGF
      protein cellular level. We also confirmed (using forskolin (20 microM) and
      phorbol 12-myristate 13-acetate (TPA) (100 nM)) that adenylate cyclase and
      protein kinase C participate in the downstream signaling responsible for the
      stimulation of BDNF synthesis, whereas in the regulation of NGF synthesis only
      the participation of protein kinase C was confirmed. Our results indicate that
      astrocyte-derived neurotrophins could play a role in distinct brain functions
      under physiological conditions and in the pathogenesis as well as possible
      treatment of different neurodegenerative disorders.

PMID- 15140466
TI  - Growth factor pre-treatment differentially regulates phosphoinositide turnover
      downstream of lysophospholipid receptor and metabotropic glutamate receptors in
      cultured rat cerebrocortical astrocytes.
AB  - Reactive gliosis is an aspect of neural plasticity and growth factor (GF)
      stimulation of astrocytes in vitro is widely regarded as a model system to study
      astrocyte plasticity. Astrocytes express receptors for several ligands including
      lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), agonists for the G
      protein-coupled lysophospholipid receptors (lpRs). Activation of lpRs by LPA or
      S1P leads to multiple pharmacological effects including the influx of calcium,
      phosphoinositide (PI) hydrolysis, phosphorylation of extracellular receptor
      regulated kinase (ERK), release of arachidonic acid, and induces mitogenesis.
      Treatment of astrocytes in vitro with a growth factor cocktail (containing
      epidermal growth factor [EGF], basic fibroblast growth factor [bFGF] and insulin)
      led to a marked attenuation of lpR-induced PI hydrolysis. In contrast, under
      identical conditions, GF treatment led to marked potentiation of PI hydrolysis
      downstream of activation of another abundantly expressed G-protein coupled
      receptor, mGluR5. Quantitative gene expression analysis of GF-treated or control
      astrocytes by TaqMan RT-PCR indicated that GF treatment did not change gene
      expression of lpa1 and s1p1, but increased gene expression of s1p5 which is
      expressed at very low levels in basal conditions. These results suggest that GF
      differentially affected PLC activation downstream of mGluR5 versus lpR activation
      and that the changes in mRNA levels of lpRs do not account for marked attenuation
      of agonist-induced phosphoinositide turnover.

PMID- 15140467
TI  - Perinatal exposure to GABA-transaminase inhibitor impaired psychomotor function
      in the developing and adult mouse.
AB  - Antiepileptic drugs acting through the potentiation of GABA-ergic pathways have
      harmful effects on brain development. Increased risk of impaired intellectual
      development was reported in children born to women treated for epilepsy during
      pregnancy. Here we examined the vulnerability of the developing brain to
      treatment with one of the new antiepileptic drugs--vigabatrin--during two time
      periods in newborn mice (postnatal days 1-7 and 4-14) which parallel the third
      trimester of human embryo brain development. Delayed development of sensory and
      motor reflexes, reduced mobility in the open field, impaired object recognition
      and deficient spatial learning and memory were observed independently of the
      treatment period. On the contrary, specific susceptibility to the age of exposure
      was detected in various motor functions. A number of morphological correlates may
      explain these behavioral alterations; a transient increase in CA1 pyramidal cell
      layer (P < 0.001) and decrease in granular cell layer (P < 0.05) in hippocampus
      were detected at postnatal day 7. In addition, a significantly lower cell density
      was observed in the adult mouse brain in all layers of the M2 cerebral cortex of
      mice treated during days 4-14, compared to the controls (P < 0.05). Our findings
      demonstrated short- and long-term deleterious effects of vigabatrin treatment and
      suggest a specific vulnerability of the developing motor system to GABA
      enhancement during the first postnatal week.

PMID- 15140468
TI  - Over-expression of bHLH genes facilitate neural formation of mouse embryonic stem
      (ES) cells in vitro.
AB  - Mouse embryonic stem (ES) cells are useful tools for investigating
      differentiation into neurons and glial cells in vitro. In order to induce ES
      cells to differentiate into neural cells, many researchers have investigated the
      efficiency of induction. Embryoid body (EB) formation and retinoic acid are
      potent differentiation inducers known to be a trigger at the early stage of
      development. Basic helix-loop-helix (bHLH) is one of the important transcription
      factors, which is essential for premature neural formation. In NeuroD2 and Mash1
      transfected cells, neural formation was observed at day 6 after the plating of
      embryoid bodies in culture. Nestin was detected in NeuroD2- and Mash1-transfected
      cells at day 10, and strong signal was detected in Mash1 transfectants by RT-PCR
      analysis. Map2 and Nurr1 were also detected strongly at the early stage in
      transfected cells compared with the wild type control, especially in the Mash1
      transfectant. In immunocytochemical analysis, Tuj1-positive neurons were detected
      at high frequency in Mash1 transfectants and some cells were stained by tyrosine
      hydrogenase (TH), a marker of dopaminergic neurons. These results demonstrate
      that bHLH has a potential activity at an early stage for ES cells and can induce
      effective and rapid neural differentiation in vitro.

PMID- 15140469
TI  - Necessity and redundancy of guidepost cells in the embryonic Drosophila CNS.
AB  - Guidepost cells are specific cellular cues in the embryonic environment utilized
      by axonal growth cones in pathfinding decisions. In the embryonic Drosophila CNS
      the RP motor axons make stereotypic pathways choices involving distinct cellular
      contacts: (i) extension across the midline via contact with the axon and cell
      body of the homologous contralateral RP motoneuron, (ii) extension down the
      contralateral longitudinal connective (CLC) through contact with connective axons
      and longitudinal glia, and (iii) growth into the intersegmental nerve (ISN)
      through contact with ISN axons and the segmental boundary glial cell (SBC). We
      have now ablated putative guidepost cells in each of the CNS pathway subsections
      and uncovered their impact on subsequent RP motor axon pathfinding. Removal of
      the longitudinal glia or the SBC did not adversely affect pathfinding. This
      suggests that the motor axons either utilized the alternative axonal substrates,
      or could still make filopodial contact with the next pathway section's cues. In
      contrast, RP motor axons did require contact with the axon and soma of their
      contralateral RP homologue. Absence of this neuronal substrate frequently impeded
      RP axon outgrowth, suggesting that the next cues were beyond filopodial reach.
      Together these are the first direct ablations of putative guidepost cells in the
      CNS of this model system, and have uncovered both pathfinding robustness and
      susceptibility by RP axons in the absence of specific contacts.

PMID- 15140470
TI  - Enhanced Ras activity in pyramidal neurons induces cellular hypertrophy and
      changes in afferent and intrinsic connectivity in synRas mice.
AB  - Neurotrophic actions are critically controlled and transmitted to cellular
      responses by the small G protein Ras which is therefore essential for normal
      functioning and plasticity of the nervous system. The present study summarises
      findings of recent studies on morphological changes in the neocortex of synRas
      mice expressing Val12-Ha-Ras in vivo under the control of the rat synapsin I
      promoter. In the here reported model (introduced by Heumann et al. [J. Cell Biol.
      151 (2000) 1537]), transgenic Val12-Ha-Ras expression is confined to the
      pyramidal cell population and starts postnatally at a time, when neurons are
      postmitotic and their developmental maturation has been basically completed.
      Expression of Val12-Ha-Ras results in a significant enlargement of pyramidal
      neurons. Size, complexity and spine density of dendritic trees are increased,
      which leads, finally, to cortical expansion. However, the main morphological
      design principles of 'transgenic' pyramidal cells remain preserved. In addition
      to somato-dendritic changes, expression of Val12-Ha-Ras in pyramidal cells
      induces augmented axon calibres and upregulates the establishment of efferent
      boutons. Despite the enlargement of cortical size, the overall density of
      terminals representing intra- or interhemispheric, specific and non-specific
      afferents is unchanged or even higher in transgenic mice suggesting a significant
      increase in the total afferent input to the neocortex. Although interneurons do
      not express the transgene and are therefore excluded from direct, intrinsic Val12
      Ha-Ras effects, they respond with morphological adaptations to structural
      changes. Thus, dendritic arbours of interneurons are extended to follow the
      cortical expansion and basket cells establish a denser inhibitory innervation of
      'transgenic' pyramidal cells perikarya. It is concluded that expression of Val12
      Ha-Ras in pyramidal neurons results in remodelling of neocortical structuring
      which strongly implicates a crucial involvement of Ras in cortical plasticity.

PMID- 15140472
TI  - Physical demands and injuries to the upper extremity associated with the space
      program.
AB  - Hand and upper-extremity overuse and repetitive injuries in astronauts have been
      and continue to be a common problem in the space program. The demands on upper
      extremity use in the astronaut training program, the zero-gravity environment,
      the extreme temperature conditions of space, the effects of space travel on human
      physiology/anatomy, and the constraints and pressures of space suits and gloves
      all can negatively impact upper-extremity function in ways that can result in
      overuse/repetitive injuries. Future plans for space exploration include endeavors
      that will continue and even increase the demands on the hand and upper extremity.

PMID- 15140473
TI  - Time course and predictors of median nerve conduction after carpal tunnel
      release.
AB  - PURPOSE: To identify predictors of outcome and of electrophysiologic recovery in
      patients with carpal tunnel syndrome (CTS) treated by endoscopic carpal tunnel
      release using a nerve conduction testing system (NC-Stat; NEUROMetrix, Inc,
      Waltham, MA). METHODS: Validity of the automated nerve conduction testing system
      was shown by comparing presurgical distal motor latencies (DMLs) against a
      reference obtained by referral to an electromyography laboratory. The DML was
      evaluated in 48 patients with CTS. Measurements were obtained within 1 hour of
      surgery and at 2 weeks, 6 weeks, 3 months, and 6 months after carpal tunnel
      release. Presurgical and postsurgical DMLs were then compared and correlated with
      variables and possible predictors of outcome including age, body mass index,
      gender, and presurgical DMLs. RESULTS: The automated nerve conduction testing
      system DMLs matched those of reference electromyography/nerve conduction study
      values with high correlation. Sensitivity of the automated nerve conduction
      testing system when compared with a standardized CTS case definition was 89%,
      with a specificity of 95%. A significant correlation was found between the DML
      before release and the DML 1 hour after release. Moreover, maximal postsurgical
      DML improvement was highly dependent on the presurgical DML, with no improvement
      shown for the <4-ms group, mild improvement for the 4-to-6-ms group, and maximal
      improvement in the >6-ms group. Among the clinical variables of age, gender, and
      body mass index only age was mildly predictive of postrelease DML changes at 6
      months. No other correlations between clinical variables and postsurgical DMLs
      were significant. In addition the predictive value of age was lost when combined
      with the presurgical DML in a multivariate analysis. CONCLUSIONS: Postsurgical
      changes in the median nerve DML were highly dependent on the prerelease latency.
      The sensitivity and specificity of a nerve conduction monitoring system in
      detecting and aiding in the diagnosis of CTS is useful in the long-term
      management of patients with CTS and can aid in determining the level of
      improvement in median nerve function after endoscopic carpal tunnel release.

PMID- 15140474
TI  - Long-term clinical and neurologic recovery in the hand after surgery for severe
      cubital tunnel syndrome.
AB  - PURPOSE: Functional outcomes of cubital tunnel surgery may decline as the
      severity of preoperative ulnar neuropathy increases. When functional recovery
      will be adequate, or whether tendon transfers should be required, may be unclear.
      We investigated the extent of functional recovery, the duration of the recovery
      process, and the necessity of restoring intrinsic muscle function in patients
      with severe cubital tunnel syndrome after surgery. METHODS: We retrospectively
      studied outcomes after cubital tunnel release in 15 patients with marked
      intrinsic muscle atrophy, claw-hand deformity, immeasurable (electrically silent)
      sensory and motor nerve conduction velocities, and Semmes-Weinstein test (SWT)
      results ranging from purple (3.84-4.31) to red (4.56-6.65). We evaluated
      subjective (numbness and activities of daily living [ADL] disturbances),
      objective (manual muscle testing [MMT] of index-finger abduction, and SWT), and
      neurophysiologic (nerve conduction velocity) outcomes. Overall functional outcome
      was evaluated by Akahori's criteria. RESULTS: At a median follow-up evaluation of
      4.5 years all outcomes had improved. Numbness was gone in 5 patients and greatly
      reduced in 9 patients; 6 patients reported slight difficulties in ADLs; and 9
      patients had no difficulties. Motor nerve conduction velocity was measurable
      (mean, 35.3 m/s) in all 15 patients and sensory nerve conduction velocity was
      measurable (mean, 43.4 m/s) in 12. Recoveries in nerve conduction velocities
      persisted beyond 2 years. The SWT results were blue (3.22-3.61) in 6 patients,
      purple (3.84-4.31) in 8 patients, and red (4.56-6.65) in 1 patient. MMT of index
      finger abduction was grade 4 or 5 in 11 of 15 patients. Half the patients over 70
      years old, however, were grade 3 or less. Akahori's criteria were excellent in 3
      patients, good in 6 patients, and fair in 6 patients. CONCLUSIONS: Patients with
      severe intrinsic muscle atrophy and absent motor and sensory nerve conduction
      velocities can expect satisfactory long-term functional results after surgery.
      Function continues to improve beyond 2 years. Restoring index finger abduction is
      not always necessary for ADLs, although recovery requires several years and is
      poorer in the elderly.

PMID- 15140476
TI  - Snapping wrist after surgery for carpal tunnel syndrome and trigger digit: a case
      report.
AB  - We present a case of snapping dislocation of the flexor digitorum superficialis
      tendon to the small finger over the hook of the hamate that was noted after
      carpal tunnel release and trigger digit release.

PMID- 15140475
TI  - Patient-reported outcome after carpal tunnel release for advanced disease: a
      prospective and longitudinal assessment in patients older than age 70.
AB  - PURPOSE: Advanced stages of nerve compression are likely to result in
      irreversible intraneural changes including intrinsic fibrosis and axon loss, and
      advanced age is expected to compromise nerve regeneration and recovery. Although
      satisfactory outcomes have been reported we hypothesized that carpal tunnel
      release in an elderly population with advanced carpal tunnel disease might not
      significantly improve symptom severity, functional status, or grip strength
      compared with before surgery. Our purpose was to evaluate these 3 parameters both
      before and after surgery to assess the efficacy of surgical intervention.
      METHODS: Between October 2000 and January 2002 a total of 13 patients (14 hands)
      were enrolled into a prospective longitudinal study. Entry criteria included
      advanced carpal tunnel syndrome based on neurophysiologic studies (absent sensory
      latencies and positive fibrillation potentials), clinical examination (thenar
      atrophy), and age over 70 years. Exclusion criteria included cervical disease,
      prior surgery, concomitant surgery, diabetic neuropathy, and associated cubital
      tunnel syndrome. There were 7 men and 6 women with an average age of 79 years
      (range, 72-90 y). With the help of a neutral observer each patient completed the
      Brigham and Women's validated carpal tunnel syndrome questionnaire before and 6
      and 12 months after surgery to assess symptom severity and functional status.
      Grip strength was measured before and at 1 year after surgery and each patient
      also was asked to rate their level of satisfaction with their outcome at 1 year
      after surgery. RESULTS: Before surgery the mean symptom severity score was 29
      based on a scale in which a minimum score of 11 reflects no symptoms and a
      maximum score of 55 reflects severe symptoms. The mean functional status score
      was 18 on a scale in which a minimum score of 8 reflects no difficulty and a high
      score of 40 reflects severe impairment. Six months after surgery the mean symptom
      severity score decreased from 29 to 15 (11 reflects no symptoms) and the average
      functional status score decreased from 18 to 11 (8 reflects no difficulty). One
      year after surgery the symptom severity score decreased from 15 to 14 and the
      functional status score decreased from 11 to 9. Compared with scores before
      surgery the improvements at 6 months and 1 year were statistically significant.
      Patient satisfaction was noted for 13 of 14 hands. Average grip strength remained
      unchanged after surgery. CONCLUSIONS: Carpal tunnel release is unlikely to result
      in a total elimination of symptoms and complete restoration of function when
      performed in elderly patients with advanced disease. Although grip strength did
      not improve at final follow-up evaluation, symptom severity and functional status
      did improve from the patient's perspective. We conclude that carpal tunnel
      release is efficacious in this subset of patients.

PMID- 15140477
TI  - Painful neuroma of the posterior cutaneous nerve of the forearm after surgery for
      lateral humeral epicondylitis.
AB  - PURPOSE: To describe a neuroma of the posterior cutaneous nerve of the forearm
      that can be the source of pain after surgery for lateral humeral epicondylitis.
      METHODS: A retrospective chart review of 9 patients having pain after surgery for
      lateral humeral epicondylitis was conducted to evaluate their history of pain,
      surgical findings during exploration of their painful lateral elbow scar, and
      outcome of their surgical treatment. RESULTS: In each of the 9 patients a neuroma
      of the posterior cutaneous nerve of the forearm was found to be within the scar
      of the original lateral epicondylitis surgery. For each of these patients the
      surgical treatment included resection of the neuroma and implantation of the
      proximal end of the nerve into the brachioradialis muscle proximal to the elbow
      joint. With this approach 8 of the patients had excellent pain relief and 1 had
      good pain relief at a mean follow-up time of 1.4 years (range, 1.0-2.6 years).
      CONCLUSIONS: Pain in the region of the scar after surgery to treat lateral
      humeral epicondylitis can be caused by a neuroma of the posterior cutaneous nerve
      of the forearm and this painful neuroma can be treated successfully by neuroma
      resection and implantation of the nerve proximally into the brachioradialis
      muscle.

PMID- 15140478
TI  - Identification of the phrenic nerve in surgical exploration of the brachial
      plexus in obstetrical palsy.
AB  - This report describes a simple technique for identifying the phrenic nerve at the
      beginning of exploration of the brachial plexus in obstetrical palsy. Both the
      phrenic and supraclavicular nerves originate from the C4 root; therefore,
      retrograde dissection of the supraclavicular nerve will end at the C4 root and
      identify the phrenic nerve. This technique is very useful to less experienced
      surgeons but may also be helpful when the experienced surgeon encounters
      excessive scarring of the anterior scalene muscle. Finally, the dissected
      supraclavicular nerve may be used as a cable graft in brachial plexus
      reconstruction.

PMID- 15140479
TI  - The accuracy of high-resolution ultrasound for evaluating focal lesions of the
      hand and wrist.
AB  - PURPOSE: Although several articles have described the sonographic features of
      solid and cystic lesions of the hand and wrist, few have investigated its
      accuracy for diagnosing such lesions. The purposes of this retrospective study
      were to determine the accuracy of sonography for diagnosing focal lesions of the
      hand and wrist against the standard of histologic examination of the resected
      specimen and to compare the accuracy of sonography against the recorded initial
      clinical impression. METHODS: A medical record search for all sonographic studies
      of the hand and wrist at our institution was performed. Eighty-four patients had
      correlative surgery and made up the study group. All sonogram reports were
      reviewed for the absence or presence of focal lesions and specific diagnoses and
      all medical records were reviewed for the initial clinical impression. Both were
      compared with histologic findings and tested for agreement with the kappa
      statistic and for significant differences with the McNemar test RESULTS: Seventy
      six of the 84 patients had focal lesions of the hand and wrist and 8 had normal
      sonograms. Overall, ultrasound correctly diagnosed 83% of the lesions and the
      initial clinical impression was correct in 54%. Of the 76 lesions ultrasound
      correctly diagnosed 87% of cystic lesions, 73% of solid lesions, 75% of
      tenosynovitis cases and the single-vessel thrombosis. The initial clinical
      impression was correct in 67% of cystic lesions and 75% of tenosynovitis cases.
      The solid or cystic nature of the 15 solid lesions and the single-vessel
      thrombosis could not be determined by history or physical examination alone. Of
      the 35 cases in which the recorded clinical impression was incorrect or not
      recorded ultrasound provided the correct diagnoses in 71% of these cases.
      Agreement with the kappa statistical analysis was only fair and the recorded
      initial clinical impression was less accurate than ultrasound. CONCLUSIONS:
      Ultrasound was statistically more accurate than the initial clinical impression
      for distinguishing solid from cystic lesions of the hand and wrist. Ultrasound
      was very accurate for specifically diagnosing ganglions and slightly less for
      solid lesions and tenosynovitis.

PMID- 15140480
TI  - Ultrasound for the early diagnosis of clinically suspected scaphoid fracture.
AB  - PURPOSE: To test the ability of ultrasound to diagnose clinically suspected
      occult scaphoid fractures. METHODS: Eighteen wrists in 18 patients with an
      average age of 35 years (range, 10-77 years) were seen in the emergency room,
      each with a single traumatic wrist injury, snuffbox tenderness, swelling, and a
      negative wrist x-ray result. They were evaluated in this prospective, blind,
      controlled study by physical examination, x-ray, and high-resolution ultrasound.
      One hand surgeon performed the examination, and ultrasounds were read by a
      musculoskeletal radiologist. Patients were immobilized in a thumb spica splint
      and then seen in the office 1 to 14 days after the emergency room visit, at which
      time a repeat physical examination, wrist x-ray, and the single investigative
      ultrasound were done using the opposite wrist as a control. All patients were
      immobilized and evaluated until symptoms resolved or x-ray showed scaphoid
      fracture site resorption or callus, in which case they were kept immobilized
      until healed. RESULTS: Ultrasound identified correctly 7 of 9 cases that were
      eventually positive for scaphoid fracture on plain x-ray. Ultrasound was read
      correctly as negative in 8 of 9 x-ray-negative cases; this was statistically
      significant. The 1 false-positive case had radioscaphoid arthrosis and radial
      wrist swelling. Sensitivity was 78% and specificity was 89%. The positive
      predictive value was 88% and negative predictive value was 80%. CONCLUSIONS: We
      recommend that high-frequency ultrasound be used to investigate occult suspected
      scaphoid fractures because of its ability to allow early diagnosis and to
      eliminate the need for a more invasive or expensive diagnostic test in most
      cases.

PMID- 15140481
TI  - Complications of wrist arthroscopy.
AB  - PURPOSE: To determine the incidence and nature of complications after arthroscopy
      of the wrist joint. METHODS: The outpatient records and surgical reports of 211
      patients who had wrist joint arthroscopy were reviewed to determine type of
      procedure, type of anesthetic, portals used, and incidence and nature of
      postsurgical complications. RESULTS: We identified a total of 11 complications in
      our patient group (5.2%). Of these, 2 patients (0.9%) developed major
      complications and 9 patients (4.3%) developed minor complications. Five
      complications 45% were identified in the immediate postsurgical period and 6
      (55%) were delayed complications. All of the minor complications resolved at
      latest follow-up evaluation with conservative care. CONCLUSIONS: Wrist
      arthroscopy is a safe procedure with a low rate of major and minor complications.
      In spite of its limitations wrist arthroscopy remains an invaluable tool in the
      diagnosis and treatment of wrist joint disorders.

PMID- 15140482
TI  - Treatment of isolated perilunate and lunate dislocations with combined dorsal and
      volar approach and intraosseous cerclage wire.
AB  - PURPOSE: To determine the clinical outcome of patients with perilunate and lunate
      dislocations treated with a combined dorsal and volar approach and intraosseous
      cerclage wire. METHODS: A combined dorsal and volar approach with an intraosseous
      wiring technique was used to treat 22 isolated perilunate and lunate
      dislocations. The mean interval between injury and surgery was 3 days. Outcome
      was assessed after an average of 49 months. Patients were assessed subjectively
      with a Disabilities of the Arm, Shoulder, and Hand questionnaire and were asked
      to rate their overall satisfaction, pain relief, problems with activities of
      daily living, and return to work and previous activity status. Results were
      assessed objectively by range of motion and grip-strength measurements and
      initial postsurgical radiographs were compared with final radiographs with regard
      to scapholunate angle and gap. RESULTS: Patient satisfaction was high in 15 of 22
      patients. Seven patients stated they had problems with activities of daily living
      after their injury. Only 10 patients returned to the same job they had before
      their injury; however, all 22 patients were able to return to some type of work.
      Sixteen of the patients stated they were able to return to their previous level
      of activity. The wrist flexion-extension arc and grip strength averaged 80% and
      77%, respectively, compared with the opposite side. Follow-up radiographs showed
      no significant change in scapholunate angle or gap with time. As expected the
      scapholunate cerclage wire broke frequently. The cerclage wire was removed in 16
      patients, 12 because of broken hardware and 4 because of pain. CONCLUSIONS: Our
      results show that a combined dorsal and volar approach with an intraosseous
      wiring technique can restore effectively normal intercarpal relationships,
      providing acceptable pain relief, functional motion, and grip strength.

PMID- 15140483
TI  - Scaphoid and lunate motion during a wrist dart throw motion.
AB  - PURPOSE: The primary purpose of this study was to measure the in vitro scaphoid
      and lunate motion during 9 different variations of a wrist dart throw motion.
      Another goal was to determine the specific dart throw motion that minimized
      scaphoid and lunate motion. METHODS: Scaphoid and lunate motion were recorded in
      7 cadaver forearms during various combinations of wrist dart throw motions caused
      by a wrist joint motion simulator. RESULTS: During wrist flexion and extension
      the scaphoid and lunate motions follow the wrist motion. During wrist radial and
      ulnar deviation the scaphoid and lunate correspondingly flex and extend. During
      intermediate motions the scaphoid and lunate move as little as 26% of the total
      third metacarpal motion and do not necessarily follow a planar motion.
      CONCLUSIONS: These findings suggest that there may be a dart throw motion during
      which there may be minimal scaphoid and lunate motion. If a subject's wrist
      motion could be clinically restricted to this dart throw motion, early hand
      mobility might be possible after surgery on the scaphoid and lunate.

PMID- 15140484
TI  - Soft-tissue stabilizers of the distal radioulnar joint: an in vitro kinematic
      study.
AB  - PURPOSE: Distal radioulnar joint (DRUJ) stability is dependent on osseous
      anatomy, soft-tissue stabilizers, and muscle activity. The relative importance of
      DRUJ soft-tissue stabilizers remains controversial and has not been examined in
      the more physiologic setting of simulated muscle loading in the intact specimen.
      The purpose of this study was to examine the role of static stabilizers on the
      kinematics of the DRUJ during active simulated motion. METHODS: Twelve cadaveric
      upper extremities underwent computer-controlled, simulated, active forearm
      rotation. Joint kinematics were measured in the intact specimen and after
      sequential sectioning of soft-tissue stabilizers including the dorsal and palmar
      radioulnar ligaments (RULs) and the triangular fibrocartilage (TFC), dorsal and
      palmar capsule, ulnocarpal ligaments (UCL), extensor carpi ulnaris (ECU)
      subsheath, pronator quadratus (PQ), and the interosseous membrane (IOM). RESULTS:
      After sectioning of soft tissues significant changes in the DRUJ kinematics were
      observed. With a distal to proximal sectioning sequence significant alterations
      in kinematics were not identified until sectioning of the IOM; with a proximal to
      distal sectioning sequence intact DRUJ kinematics were maintained until the final
      soft-tissue (RULs and TFC) sectioning. CONCLUSIONS: Sectioning of all soft-tissue
      stabilizers produced significant DRUJ instability and abnormal joint kinematics.
      The RULs and TFC play a key role in DRUJ kinematics because they can help to
      maintain normal joint rotation in the absence of all other soft-tissue
      stabilizers. With the preservation of other soft-tissue stabilizers, however, the
      RULs and TFC are not essential for the maintenance of normal kinematics of the
      DRUJ.

PMID- 15140485
TI  - Mechanoreceptors and nerve endings of the triangular fibrocartilage in the human
      wrist.
AB  - PURPOSE: To increase our understanding of the mechanism of pain and the sensation
      of wrist instability by studying the distribution of the mechanoreceptors in the
      triangular fibrocartilage (TFC). METHODS: The distribution and density of the
      nerve endings were investigated in 34 TFC specimens obtained from human cadavers.
      We studied the dorsal, palmar, ulnar, radial, and central areas after staining by
      a modified gold chloride technique. RESULTS: The free nerve endings, responsible
      for sensing pain, predominate in the ulnar and dorsal areas. The Vater-Pacini
      corpuscles predominate in the radial and dorsal area, promoting perception of the
      onset or cessation of movement and mechanical stress change. The Golgi-Mazzoni
      corpuscles were more frequent in the ulnar and ventral areas, linking these areas
      to function of slow adaptation and sensation of extreme movements. The
      proprioceptive function receptors were found in all areas of TFC because Ruffini
      corpuscles have homogeneous distribution in this fibrocartilaginous tissue.
      CONCLUSIONS: Our results showed that the nerve endings were distributed at the
      periphery of TFC and showed different concentrations of each type of
      mechanoreceptors per topographic area, suggesting that they play specific roles
      in the proprioceptive and nociceptive reflexes of the wrist.

PMID- 15140487
TI  - Volar Barton's fractures with concomitant dorsal fracture in older patients.
AB  - PURPOSE: To describe a variant of Barton's volar articular shearing fracture of
      the distal radial articular surface with a subtle concomitant fracture of the
      dorsal metaphyseal cortex. METHODS: This fracture pattern was observed in 6 women
      and 2 men with an average age of 67 years (range, 58-76 years). All 8 patients
      were treated with a volar plate and screws. The dorsal metaphyseal fracture was
      not recognized in 5 patients and a volar buttress plating technique using an
      intentionally undercontoured volar plate was used. In 3 patients the dorsal
      fracture line was identified before surgery and the plate was contoured to fit
      the volar surface of the distal radius. RESULTS: All 5 patients treated with an
      undercontoured plate had loss of the normal palmar tilt of the distal radius
      (average,-9.4 degrees; range, 0 degrees to-22 degrees ) and dorsal translation of
      the distal radial articular fragments. For the entire group the palmar tilt
      averaged-5.9 degrees (range, 0.0 degrees to-22.0 degrees ), the ulnar inclination
      19 degrees (range, 10 degrees -23 degrees ), and the ulnar variance-0.9 mm
      (range, 0.0 to-3.0 mm). All patients attained forearm supination of 80 degrees
      and the average pronation was 75 degrees (range, 45 degrees -80 degrees ).
      According to Sarmiento's modification of the system of Gartland and Werley there
      were 1 excellent, 6 good, and 1 fair results. The average Patient-Rated Wrist
      Evaluation score was 16 (range, 0-35). CONCLUSIONS: Some fractures with an
      oblique volar marginal articular fracture of the distal radius and volar
      radiocarpal subluxation (known as Barton's fracture) may also have a fracture
      through the dorsal metaphyseal cortex. Failure to identify this fracture line can
      lead to dorsal translation and angulation of the distal radius articular surface,
      particularly when an undercontoured volar plate is used for internal fixation.

PMID- 15140488
TI  - Biomechanics in uniaxial compression of three distal radius volar plates.
AB  - PURPOSE: A new fixed-angle volar plate for a dorsally displaced distal radius
      fracture was designed with the aim of avoiding soft tissue problems due to dorsal
      plating. The purpose of this study was to compare the biomechanical properties of
      this new plate with 2 existing volar plates in a cadaver model. METHODS: Three
      different plates were applied on surgically simulated unstable extra-articular
      distal radius fractures in formalin-fixed cadaver radiuses. Group 1 (volarly
      placed AO titanium Distal Radius plates [Synthes Ltd, Paoli, PA]; n = 6), group 2
      (volarly placed titanium Symmetry plates [DePuy ACE Co, El Segundo, CA]; n = 6),
      and group 3 (volarly placed newly designed titanium plates; n = 6) were tested to
      failure under axial compression with a materials testing machine. Specimens of
      all 3 groups had similar bone mineral density. RESULTS: Group 3 specimens had
      significantly greater elastic limit and ultimate strength than the other 2
      groups. Specimens of group 3 had the greatest rigidity, although this was
      statistically insignificant compared with the other 2 groups. All plates (groups
      1, 2, 3) failed in apex volar angulation. CONCLUSIONS: The newly designed plate
      fixation system is the strongest of the systems tested and may offer adequate
      stability for the treatment of a distal radius fracture in which the dorsal
      and/or volar metaphyseal cortex is comminuted severely.

PMID- 15140489
TI  - Self-reinforced bioabsorbable miniplates for skeletal fixation in complex hand
      injury: three case reports.
AB  - We report our preliminary experience with 3 cases in which internal fixation with
      a self-reinforced poly-l/dl-lactide 70/30 miniplate and 1.5-mm or 2.0-mm screws
      were used to stabilize an open metacarpal fracture, a metacarpophalangeal
      arthrodesis in a thumb replantation, and an interposed bone graft for
      reconstruction of a thumb. Clinical and radiologic follow-up evaluation lasted
      for 12 to 20 months. Bone healing was uneventful in all 3 cases with no
      displacement or delayed union. The implants were biocompatible with no clinically
      manifested foreign body reaction. Because of the self-reinforcing manufacturing
      technique the plates have metal-like mechanical and handling properties. Complete
      late resorption makes self-reinforced poly-l/dl-lactide 70/30 miniplating systems
      an attractive alternative to metallic implants for skeletal stabilization of
      small bones of the hand.

PMID- 15140490
TI  - Remodeling of phalangeal neck fracture malunions in children: case report.
AB  - We report a case of a malunion of a proximal phalanx neck fracture in a 5-year
      old boy that remodeled nearly completely, resulting in excellent proximal
      interphalangeal joint motion and function.

PMID- 15140491
TI  - The Steindler flexorplasty for the arthrogrypotic elbow.
AB  - PURPOSE: The arthrogrypotic elbow often lacks active flexion. If active elbow
      flexion can be provided by muscle transfer, patient independence increases and
      the patient can function in a less conspicuous manner by avoiding adaptive
      mechanisms. The purpose of this article is to review the outcome of patients with
      arthrogryposis treated with the Steindler flexorplasty to obtain active elbow
      flexion. METHODS: Seventeen elbows in 10 patients with an average age of 7 years
      were treated surgically with the Steindler flexorplasty procedure. Before surgery
      none of the patients was able to flex actively the elbow against gravity. All of
      the patients had at least 70 degrees of passive elbow flexion. Upper-extremity
      active and passive range of motion, strength of flexion, functional outcome, and
      patient satisfaction were assessed at an average of 5 years after surgery (range,
      2-9 years). RESULTS: After surgery all patients obtained active elbow flexion
      against gravity averaging 85 degrees (range, 30 degrees -120 degrees ); patients
      were able to lift an average of 1 kg through their entire arc of elbow flexion.
      At last follow-up evaluation patients lost an average of 27 degrees of elbow
      extension. Patients lost forearm rotation but did not lose wrist or finger range
      of motion. Subjectively, 9 of the 10 patients were satisfied with the outcome of
      the surgery and would recommend the surgery to others. CONCLUSIONS: The Steindler
      flexorplasty provides improved elbow flexion strength and patient function and
      should be considered for children with arthrogryposis.

PMID- 15140492
TI  - Surgical treatment of persistent dislocation or subluxation of the ulnohumeral
      joint after fracture-dislocation of the elbow.
AB  - PURPOSE: To review the results of surgical reconstruction of posttraumatic elbow
      instability in the setting of either intact or repaired olecranon process using a
      protocol incorporating hinged elbow fixation. METHODS: Thirteen consecutive
      patients with ulnohumeral instability after a fracture-dislocation of the elbow,
      adequate articular surfaces, and adequate, stable alignment of the olecranon were
      treated with temporary hinged external fixation, preservation, or reconstruction
      of both the coronoid process and radiocapitellar contact and with repair or
      reconstruction of the lateral collateral ligament complex. There were 9 men and 4
      women with an average age of 45 years. Seven patients had a terrible triad
      pattern injury and 6 had a posterior Monteggia pattern injury. All 13 patients
      had fracture of the radial head and 10 patients had fracture of the coronoid
      process. RESULTS: At an average follow-up period of 57 months stability was
      restored in every patient. The average Disabilities of the Arm, Shoulder, and
      Hand questionnaire score was 15 and the average Mayo score was 84, with 6
      excellent, 4 good, and 3 fair results. The average arc of ulnohumeral motion was
      99 degrees. Six patients had radiographic signs of arthrosis including 5 of 6
      patients with olecranon fracture-dislocations. CONCLUSIONS: A stable, functional
      elbow can be restored in most patients with persistent instability after fracture
      dislocation of the elbow using a treatment protocol incorporating hinged external
      fixation.

PMID- 15140493
TI  - Effects of the adductor pollicis and abductor pollicis brevis on thumb
      metacarpophalangeal joint laxity before and after ulnar collateral ligament
      reconstruction.
AB  - PURPOSE: The intrinsic muscles and ulnar capsuloligamentous structures (UCLS),
      which consist of the ulnar collateral ligament (UCL), accessory UCL, dorsal
      capsule, and volar plate of the thumb metacarpophalangeal (MCP) joint are
      important for controlling the motion and stability of the MCP joint during pinch.
      The purpose of this cadaveric study was to determine the effects of the adductor
      pollicis (AdP) and abductor pollicis brevis (APB) on the 3-dimensional MCP joint
      laxity before transection of the UCLS and after reconstruction of the UCL and
      repair of the dorsal capsule. METHODS: Loads were applied to the flexor pollicis
      longus (FPL) alone, to the AdP and FPL in combination, and to the APB and FPL in
      combination in 11 cadavers. This was done in the intact joint after the UCLS were
      transected and after the UCL was reconstructed for flexion angles of 0 degrees,
      15 degrees, 30 degrees, and 45 degrees. The spatial positions of the proximal
      phalanx and the metacarpal of the MCP joint were measured with a 6-degrees-of
      freedom digitizing system. RESULTS: In the intact joint combined loading of the
      AdP and FPL did not affect the position of the proximal phalanx. Combined loading
      of the APB and FPL changed the position of the phalanx from an ulnar to a radial
      shift and from an ulnar to a radial deviation and it increased pronation. After
      transection of the UCLS combined loading of the FPL and AdP increased supination
      of the MCP joint and combined loading of the FPL and APB increased radial shift,
      radial deviation, and pronation of the joint. Reconstruction of the UCL restored
      normal laxity to the MCP joint. CONCLUSIONS: The AdP failed to affect MCP joint
      motion. The ABP produced a radial shift and radial deviation of the MCP joint and
      increased pronation of the thumb. Transection of the UCLS increased joint laxity
      for each of the combined loadings and reconstruction of the UCL restored normal
      laxity to the MCP joint.

PMID- 15140494
TI  - Clinical indicators of normal thumb length in adults.
AB  - PURPOSE: This study was undertaken to obtain clinical indicators of normal
      relative thumb length in adults. METHODS: Fifty two normal hands in 26 volunteers
      were analyzed. There were 10 women and 16 men. The average age was 34 years
      (range, 23-47 years). Eighteen of the volunteers (36 hands) were Chinese and 8
      were Caucasian (16 hands). All the subjects were healthy with no history of
      trauma or disease affecting the hand. The relative distal extent of the tip of
      the thumb was measured against 2 parameters: the length of the proximal phalanx
      of the index finger and the distance between the proximal digital crease and
      proximal interphalangeal crease of the index finger. The obtained values were
      designated as the thumb-proximal phalanx (TPP) index and the thumb-digital crease
      (TDC) index, respectively. RESULTS: The TPP index was 0.69 (standard deviation =
      0.09) and the TDC index was 0.41 (standard deviation = 0.15). There were no
      statistically significant differences between the right and left hands nor were
      there any between male and female hands. It was also noticed that when the thumb
      was adducted the thenar crease and thumb interphalangeal crease came into contact
      with one another in 90% of the hands. Consequently, an arc traced along the
      thenar crease could be extended smoothly into the interphalangeal crease of the
      thumb. This was termed the thenar arc. Positive or negative variances of the
      thenar arc correlated statistically with variations of the TPP and TDC indexes.
      CONCLUSIONS: This study provides 3 simple clinical indicators of normal thumb
      length: the TPP index, the TDC index, and the thenar arc. Statistical analysis of
      the TPP and TDC indexes showed that the values are independent of gender, race,
      or laterality of the hands examined. These 3 indicators may help the clinician
      determine normal relative thumb length when reconstructing the thumb in adults.

PMID- 15140495
TI  - The septa of Legueu and Juvara: an anatomic study.
AB  - PURPOSE: To study the anatomy of the septa of Legueu and Juvara and interpalmar
      plate ligaments (IPPLs) of the hand. MATERIALS: Eleven cadaver hands were
      dissected. The number, attachments, dimensions, and relationships of the septa
      and IPPLs to other structures were determined. RESULTS: Eight septa were
      identified radial and ulnar for each digit. The radial were longer than the ulnar
      septa. The septa attached to the transverse ligament of the palmar aponeurosis
      superficially and to the soft-tissue confluence deeper and distally. They formed
      7 compartments of 2 types flexor septal canals that contained the flexor tendons
      and web space canals that contained common digital nerves and arteries and
      lumbrical muscles. Grossly and histologically the septa were thicker and
      consisted of organized collagen distally but not proximally. Three IPPLs were
      identified: radial, central, and ulnar. These formed the floors of the second,
      third, and fourth web space canals. The IPPLs were more substantial, thicker, and
      had more fibrous appearance from radial to ulnar. The fibers of the radial and
      central IPPLs were oriented transversely, whereas those of the ulnar IPPL were
      oriented obliquely. CONCLUSIONS: Awareness of the anatomy of deep retinacular
      structures of the hand is important for surgical exposure in this area and
      possible involvement in conditions such as Dupuytren's disease.

PMID- 15140496
TI  - Anatomic study of variations of hypothenar muscles and arborization patterns of
      the ulnar nerve in the hand.
AB  - PURPOSE: To show the variations in the hypothenar muscles and the arborization
      patterns of the ulnar nerve and to investigate the relationship between the
      hypothenar muscles and the ulnar nerve. METHODS: We performed an anatomic study
      of 35 hands from embalmed cadavers. After dissecting the ulnar side of the hand
      we recorded the number of hypothenar muscles and their variations, the site of
      the hiatus for the deep branch of the ulnar nerve, and the branching patterns of
      the ulnar nerve in each hand. We then investigated the relationship between the
      variations in the hypothenar muscles and the arborization patterns of the ulnar
      nerve. RESULTS: The abductor digiti minimi (ADM) had 1 belly in 6 hands, 2
      bellies in 28 hands, and 3 bellies in 1 hand. The flexor digiti minimi brevis was
      absent in 8 hands, had 1 belly in 24 hands, and had 2 bellies in 3 hands. The
      opponens digiti minimi had 2 layers of origin and the deep branch of the ulnar
      nerve passed between these 2 layers in all hands. We classified the structural
      patterns of the hiatus into 3 types, the arborization patterns of the ulnar nerve
      into 5 types, and the branching patterns of the motor branch to the ADM into 4
      types according to their morphologic characteristics. We found variations of the
      arborization pattern in which the deep branch originated from the ulnar trunk of
      the ulnar nerve distal to bifurcation in 3 hands, a communicating branch was
      present between the 2 sensory branches to the fingers in 3 hands, and the ulnar
      sensory branch pierced the ADM in 2 hands. CONCLUSIONS: We confirmed that the
      anatomic relationship between the ulnar nerve and the hypothenar muscle is
      complex and that the formation of the hiatus varies. This knowledge can assist
      the surgeon in the diagnosis and treatment of conditions associated with the
      ulnar aspect of the hand.

PMID- 15140497
TI  - Abductor digiti minimi involvement in Dupuytren's contracture of the small
      finger.
AB  - PURPOSE: Dupuytren's contracture (DC) is a common, benign, progressive condition.
      Patterns of involvement of the ulnar side of the hand, specifically the
      involvement of the abductor digiti minimi (ADM), have received limited attention;
      therefore, the purpose of this study was to determine the prevalence, patterns of
      involvement, and surgical outcomes in DC of the small finger. METHODS: A
      retrospective review was performed on the hands of all patients who had surgery
      for DC between January 1998 and March 2002 to determine the incidence of ADM
      involvement. RESULTS: A total of 149 patients had 195 surgeries on 261 digits
      during this period. Forty-seven percent of cases involved the small finger and
      27% of those involved the ADM. Those cases involving the ADM had statistically
      significantly greater mean preoperative proximal interphalangeal joint (PIPJ)
      contracture (53 degrees ) as well as postoperative PIPJ contracture (34 degrees )
      when compared with those without ADM involvement of the small finger (31 degrees
      preoperative PIPJ contracture and 15 degrees postoperative PIPJ contracture,
      respectively). The most common origin pattern of the ADM involvement was found to
      arise from both the ADM tendon and overlying fascia (77%). The most common
      insertion pattern was found to be over the middle phalanx (50%). CONCLUSIONS: We
      conclude that ADM is involved in DC of the small finger in one quarter of cases.
      Failure to recognize and resect the diseased cord arising from it and its
      overlying fascia at the time of surgery may account for the poor outcomes seen in
      DC of the small finger.

PMID- 15140498
TI  - Measuring grip strength in normal adults: reference ranges and a comparison of
      electronic and hydraulic instruments.
AB  - PURPOSE: To determine reference ranges for peak, average, and final adult grip
      strength over 10 seconds by using an electronic dynamometer, and to compare
      results from hydraulic and electronic dynamometers. METHODS: The hand-grip
      strengths of 476 healthy adult subjects were tested using the electronic
      (Grippit; AB Detektor, Goteborg, Sweden) and hydraulic (Jamar; Smith and Nephew,
      Memphis, TN) dynamometers. RESULTS: Age- and gender-specific reference ranges for
      the Jamar and Grippit dynamometers are presented. Bland-Altman analysis of the
      differences between the results obtained using the 2 instruments revealed a bias
      (mean difference) of 22 N (Jamar - Grippit) and limits of agreement of -86 to 129
      N (mean +/- 2 SD), which indicates that grip measurements may vary by up to 215 N
      between instruments. CONCLUSIONS: The study yielded population reference ranges
      of peak, average, and final strength over a 10-second grip assessment using an
      electronic dynamometer. Results from the Grippit and Jamar dynamometers are
      similar; however, the dynamometers cannot be interchanged. The Grippit provides
      information about endurance and fatigue of grip over 10 seconds, showing
      differences between right- and left-dominant adults.

PMID- 15140499
TI  - Bizarre parosteal osteochondromatous proliferation (Nora's lesion) in the hand.
AB  - PURPOSE: The purpose of this study was to review our experience with a benign
      surface bone lesion referred to as bizarre parosteal osteochondromatous
      proliferation (BPOP) or Nora's lesion, named for the pathologist who described it
      in 1983. The lesion may be confused with a variety of tumors, particularly
      solitary osteochondromas, which are rare. METHODS: The files in the Department of
      Pathology at the Hospital for Joint Diseases were reviewed over a 21-year period
      for all surface bone lesions involving the tubular bones in the hand. There were
      a total of 10 cases of BPOP compared with only a single case of an
      osteochondroma. RESULTS: Radiographs generally showed a well-marginated uniformly
      dense mass arising from the surface of the affected bone without any disruption
      in its bony architecture. Surgical excision is the definitive treatment and
      included the fibrous pseudocapsule over the lesion, any periosteal tissue beneath
      the lesion, and any area of the cortex of the host bone that appeared abnormal.
      Although in the medical literature the recurrence rate for BPOP is high, we had
      only one recurrence in our series. CONCLUSIONS: BPOP is a benign surface bone
      lesion that may be confused with benign and malignant tumors. Although there is a
      cleavage plane between the lesion and host bone, we recommend excising the
      pseudocapsule over the lesion, any periosteal tissue beneath the lesion, and
      decorticating any abnormal-appearing areas in the underlying host bone. This may
      explain the low recurrence rate in our series.

PMID- 15140500
TI  - Gouty flexor tenosynovitis of the digits: report of three cases.

PMID- 15140503
TI  - Antiphospholipid syndrome and second- or third-trimester fetal death: follow-up
      in the next pregnancy.
AB  - OBJECTIVE: To evaluate the efficacy of a uniform management protocol in
      antiphospholipid-antibody-positive obstetric patients with at least one second-
      or third-trimester intra-uterine fetal death. STUDY DESIGN: A prospective study
      of 33 successive pregnancies in antiphospholipid-antibody-positive patients,
      diagnosed after an intra-uterine fetal death. The management included treatment
      by a combination of aspirin and low-molecular-weight heparin, and a close follow
      up with at least clinical examination, ultrasonography, uterine, and umbilical
      artery Doppler monthly from the first trimester. In the absence of any anomaly,
      delivery was induced between 37 and 38 weeks' gestation. RESULTS: In this high
      risk population, seven recurrences of vascular pathology occurred: five cases of
      mild, isolated fetal growth retardation and one of preeclampsia associated with
      fetal growth retardation requiring preterm delivery. Eight patients were
      delivered before 37 weeks. No recurrence of second- or third-trimester fetal
      death was observed. Uterine artery Doppler was informative as early as the first
      trimester (12-15 weeks): a bilateral notch was associated with a lower
      birthweight (2626+/-688 g versus 3178+/-353 g, respectively, p = 0.01), despite
      similar gestational age. The negative predictive value of uterine Doppler was
      more than 92% at 12-15 weeks' gestation and remained high throughout pregnancy.
      CONCLUSION: Although intra-uterine fetal death is considered at high risk of
      recurrence in case of antiphospholipid syndrome (APS), a uniform management
      protocol including aspirin and heparin and close obstetrical follow-up led to a
      favorable outcome in most cases.

PMID- 15140504
TI  - Obstetrical complications and subsequent schizophrenia in adolescent and young
      adult offsprings: is there a relationship?
AB  - Schizophrenia is a psychiatric disease affecting around 1% of the population, the
      negative signs of which are correlated with inactivity of the prefrontal
      dorsolateral cortex, while an increased, more deeply localized, activity in the
      mesolimbic pathway may explain the positive signs. Several events occurring
      during pregnancy are likely to be involved in its genesis: hormonal
      supplementation by diethylstilbestrol, severe maternal denutrition, exposure to
      influenza virus, repeated psychological stress. From multicentric studies and
      meta-analyses in the psychiatric literature, the risk of schizophrenia appears to
      be multiplied by two if pregnancy is complicated, mainly by diabetes, Rhesus
      incompatibility, bleeding, preeclampsia, premature rupture of membranes and
      preterm birth. When delivery is linked to an abnormal presentation or happens via
      a caesarean birth for acute foetal distress, the time when the first signs of
      psychosis appear seems to be earlier in adolescence or in early adulthood.
      Cerebral imaging of schizophrenic patients shows ventriculomegaly and gray matter
      reduction, mainly in hippocampal volumes and in the dorsolateral prefrontal
      cortex. Similar alterations in the neuronal pathways have been experimentally
      reproduced in rats after repeated prenatal stress and perinatal hypoxia. A region
      on the distal portion of chromosome 1 has shown evidence for linkage to
      schizophrenia. Therefore, a two factor model seems to be able to explain the
      onset of schizophrenia in which obstetrical complications may interact with a
      genetic liability and in which the consequences of hypoxic events may lie on a
      continuum ranging from cerebral palsy in some children to subtle cognitive and
      behavioural disturbances in others.

PMID- 15140505
TI  - Redistribution of power spectrum of heart rate variability during acute umbilical
      artery embolism and hypoxemia in late-gestation fetal sheep.
AB  - OBJECTS: Fetal heart rate variability (HRV) is subject to a number of factors,
      including fetal distress. The aim of this study was to investigate the power
      spectral distribution of fetal heart rate variability during acute hypoxemia
      following umbilical artery embolism and to test the hypothesis that the relative
      proportion of frequency domains in total power of HRV, reflects the changes in
      HRV during hypoxemia more closely than the absolute values. METHODS: Acute
      hypoxemia was induced in seven catheterized late-gestation fetal sheep by
      repeated injections of microspheres to cause umbilical artery embolism. The very
      low, low-, middle- and high-frequency domains (0-0.025, 0.025-0.125, 0.125-0.20,
      and 0.20-0.50 cycles/beat, respectively) were determined by power spectral
      analysis. RESULTS: Umbilical artery embolism induced marked fetal hypoxemia,
      hypercapnia and acidosis, accompanied by an increase in heart rate and a decrease
      in arterial blood pressure. These changes were associated with the increase in
      power over the entire frequency range and in the relative power in the low
      frequency range (P<0.01), and with decrease in the relative power in the high
      frequency range (P<0.05). Correlations were found between the relative power in
      the low- and high-frequency ranges and PO2 and between the relative power in
      these ranges and mean arterial blood pressure (P<0.05), but not PCO2 or pH.
      CONCLUSIONS: The present study indicates that acute hypoxemia induced by
      umbilical artery embolism leads to the redistribution of power spectral density
      of fetal HRV and that the relative proportion of individual frequency domains may
      reflect the changes in HRV during acute hypoxemia more closely than the absolute
      power values.

PMID- 15140506
TI  - Maternal mortality in Italy, 1980-1996.
AB  - OBJECTIVE: To establish the extent of maternal mortality in Italy in between 1980
      and 1996 in order to compare it with the international data. STUDY DESIGN: We
      conducted a retrospective study on maternal deaths in Italy from 1980 to 1996.
      Data have been collected by Italian Statistic Institute (ISTAT). We calculated
      both the maternal mortality rates and the percentages of causes of death in the
      whole period, according to WHO definitions. RESULTS: The data confirmed the
      trends of the previous decade: maternal mortality rates have decreased from 13.25
      (1980) to 3.78 (1996) for 100000 live births. Haemorrhage and hypertension have
      been the main causes of maternal death, while pulmonary embolism has had a minor
      affect on maternal mortality rates compared to other countries, particularly in
      Europe. CONCLUSION: Italian data appear reassuring and encourage further
      investigations on detailed welfare problems.

PMID- 15140507
TI  - Distribution of causes of maternal mortality during delivery and post-partum:
      results of an African multicentre hospital-based study.
AB  - OBJECTIVE: To assess the maternal mortality ratio in maternity units of reference
      hospitals in large west African cities, and to describe the distribution of
      complications and causes of maternal deaths. STUDY DESIGN: Prospective
      descriptive study in twelve reference maternities located in three African
      countries (Benin, Ivory Coast, Senegal). Data (clinical findings at hospital
      entry, medical history, complications, type of surgery, vital status of the women
      at discharge) were collected from obstetrical and surgical files and from
      admission hospital registers. All cases of maternal deaths were systematically
      reviewed by African and European staff. RESULTS: Of a total of 10,515 women, 1495
      presented a major obstetric complication with dystocia or inappropriate
      management of the labour phase as the leading cause. Eighty-five maternal deaths
      were reported, giving a global hospital-based maternal mortality ratio of
      800/100,000. Hypertensive disorders were involved in 25/85 cases (29%) and post
      partum haemorrhage in 13/85 cases (15%). Relatively few cases (14) of major
      sepsis were reported, leading to three maternal deaths. CONCLUSION: The results
      of this multicentre study confirm the high rates of maternal mortality in
      maternity units of reference hospitals in large African cities, and in addition
      to dystocia the contribution of hypertensive disorders and post-partum
      haemorrhage to maternal deaths.

PMID- 15140508
TI  - Renal function and lipid metabolism in pregnant renal transplant recipients.
AB  - OBJECTIVE: To estimate renal function and lipid metabolism in pregnant renal
      transplant recipients. STUDY DESIGN: The study covered 64 women during the third
      trimester of pregnancy including 33 renal transplant recipients (the study group)
      and 31 healthy women (the control group). Serum concentrations of uric acid,
      urea, creatinine, electrolytes, total protein, albumin, acid-base balance and
      blood cell count were examined to assess renal function. Moreover, the levels of
      the following lipid metabolism parameters were estimated: (1) total lipids (TL),
      (2) total LDL fraction (TLDL), (3) total cholesterol (TCh), (4) free cholesterol
      (fCh), (5) free/total cholesterol (fCh/TCh) ratio, (6) phospholipids (PhL), (7)
      total cholesterol/phospholipids (fCh/PhL) ratio, (8) triglycerides (TG), (9) HDL
      cholesterol (HDL-Ch), (10) LDL-cholesterol (LDL-Ch) and (11) LDL-Ch/HDL-Ch ratio.
      'The effect of immunosuppressants (cyclosporine, prednisone and azathioprine) on
      serum lipid levels was estimated in the study group. The mean maternal age,
      gestational age and BMI did not differ in both groups. RESULTS: Pregnant renal
      transplant recipients presented mild renal insufficiency during the third
      trimester resulting in the increase in serum level of uric acid (P<0.001), urea
      (P<0.001), creatinine (P<0.001), and Cl- (P<0.001). Proteinuria (1.19+/-1.9 g/24
      h) leading to hypoproteinemia (P<0.001) and hypoalbuminemia (P<0.05) confirmed
      renal function impairment in the study group. Additionally, the diagnosis of
      renal insufficiency was supported by mild acidosis reflected by a drop in pH
      (P<0.001). standard HCO3- (P<0.001) and base excess (P<0.001). The women with
      renal grafts presented vital lipid metabolism disturbances illustrated by the
      elevated levels of: (1) TL by 72% (P<0.001), (2) TLDL by 21% (P<0.001), (3) TCh
      by 16% (P<0.001), (4) fCh by 34% (P<0.001), (5) fCh/TCh ratio by 21% (P<0.001),
      (6) PhL by 28% (P<0.001), (7) TG by 53% (P<0.001), (8) LDL-Ch by 13% (P<0.05) and
      (9) LDL-Ch/HDL-Ch ratio by 23% (P<0.001). No difference in HDL-Ch level between
      the two groups was found. Hyperlipidemia in pregnant kidney recipients was
      associated with immunosuppressive treatment and depended on cyclosporine
      treatment regimen. Treatment with azathioprine and prednisone was associated with
      elevated serum levels of examined lipids. CONCLUSION: Serum lipid abnormalities
      are significantly influenced by the administered dosages of immunosuppressants.

PMID- 15140509
TI  - Amniotic levels of nitric oxide and vascular endothelial growth factor in
      pregnancy with subsequent intrauterine fetal death.
AB  - OBJECTIVE: Nitric oxide (NO) and vascular endothelial growth factor (VEGF)
      regulate angiogenesis and seem involved in the early stages of placentation. If
      angiogenesis is reduced, this may lead to poor placentation and fetal death. This
      study was aimed to determine whether VEGF and NO are associated to subsequent
      fetal death. STUDY DESIGN: We retrospectively assessed NO and VEGF on
      midtrimetster amniotic fluid from seven women who had subsequently had
      intrauterine fetal death before 20 weeks, and compared the results with those of
      14 controls matched for age and gestation. All women had undergone amniocentesis
      for maternal age. All were at 16 weeks of gestation. None had shown chromosomal
      abnormalities. Results (mean+/-S.D.) were tested for statistics with Student's t
      test with significance at P<0.05. RESULTS: Women with subsequent fetal death had
      both amniotic NO and VEGF lower than women with normal pregnancy (NO 3.28+/-1.20
      microg/mg creatinine versus 6.02+/-1.57 microg/mg creatinine, P<0.05; VEGF
      210.10+/-69.55 pg/ml versus 255.05+/-88.66 pg/ml). CONCLUSIONS: An early
      reduction of both NO and VEGF may be responsible of an impaired placental
      vascular development and endothelial regulation that may lead to fetal death.

PMID- 15140510
TI  - Active induction management of labor for diabetic pregnancies at term; mode of
      delivery and fetal outcome--a single center experience.
AB  - OBJECTIVES: To evaluate the mode of delivery in diabetic pregnancies at term
      following induction of labor with vaginal application of prostaglandin E2 (PGE2),
      and to identify possible predictors of successful vaginal delivery. PATIENTS AND
      METHODS: The study group consisted of 105 women with diabetic pregnancies at term
      admitted for induction of labor; 84 (80%) had gestational diabetes (GDM) and 21
      (20%) type 1 diabetes. Findings were compared with women who underwent elective
      induction of labor (n=115), and women with normal spontaneous onset of labor
      (n=510). Women with previous cesarean section (CS) were excluded from both study
      and control groups. RESULTS: Maternal age and gravidity were significantly higher
      in the study group than the control groups (age: 31.4+/-5, 28+/-5.0 and 28.1+/
      4.8 years, respectively; gravidity: 3.0+/-1.9, 2.5+/-1.6, and 2.1+/-1.4,
      respectively; P<0.001 for both) and gestational age and nulliparity rate were
      significantly lower (gestational age: 38.6+/-1.1, 40.2+/-1.3 and 39.3+/-2.7
      weeks, respectively; nulliparity: 34.6, 45.2, 51.6%, respectively; P<0.002 for
      both). There were no between-group differences in the incidence of
      oligohydramnios, number of PGE2 applications used, birth weight, rate of non
      reassuring fetal heart rate pattern leading to CS, and rate of low 5 min Apgar
      score (<7). The rate of CS in the study group (18.2%) was significantly higher
      than in the spontaneous labor group (9%) but similar to the elective induction
      group (14.8%). On stepwise analysis, only nulliparity (OR 4.56, 95% CI 1.11
      18.67, P=0.035) was independently and significantly associated with increased
      risk of CS. Within the study group (R2=0.257, P=0.002), type 1 diabetes (OR 2.4,
      95% CI 1.04-5.51) was independently and significantly associated with increased
      risk of CS. CONCLUSION: In diabetic pregnancies, induction of labor at term with
      vaginal PGE2 is successful in approximately 82% of patients, but yields a
      significantly higher CS rate compared to uncomplicated pregnancies. Nulliparity
      and diagnosis of type 1 diabetes are independently and significantly associated
      with increased risk of CS. CONDENSATION: In diabetic pregnancies, induction of
      labor at term is successful in 82% of patients, but yields higher CS rates
      compared to uncomplicated pregnancies.

PMID- 15140511
TI  - Thickening of the amnion basement membrane and its relationship to placental
      inflammatory lesions and fetal and maternal disorders.
AB  - OBJECTIVE: The aim of this study is the morphological and morphometric analysis
      of the basement membrane amniotic epithelium of the chorionic plate to establish
      possible correlation between the basement membrane amniotic epithelium thickening
      and maternal and fetal disorders. STUDY DESIGN: Ninety-one placentas of infants
      delivered in Medical Hospital School were studied with hematoxylin-eosin (H&E)
      and Periodic Acid Schiff (PAS) methods, morphometric and ultrastructural
      analysis. RESULTS: Of the 91 placentas analyzed, 17 (18.6%) were normal with
      regard to placental morphology, fetal and maternal history. Basement membrane
      amniotic epithelium thickening was significantly greater in the cases associated
      with chorioamnionitis (P=0.013), villitis (P=0.040), maternal hypertension
      syndromes during pregnancy (P=0.027) and stillborn (P=0.040) babies. The electron
      microscopic examination of the basement membrane amniotic epithelium identified a
      structural alteration and edema of the dense lamina. CONCLUSION: Thickening of
      the basement membrane amniotic epithelium was associated with morphologic
      placental abnormalities and/or fetal or maternal disorders. Thickening of the
      basement membrane amniotic epithelium was identified away from the site of
      placental inflammation, possibly being a consequence of cytokines, supporting
      more than a local effect. This could be a new insight into the pathogenesis of
      fetal and maternal complications associated with inflammatory placental lesions.

PMID- 15140512
TI  - Changes of serum paraoxonase (an HDL-cholesterol-associated lipophilic
      antioxidant) and arylesterase activities in severe preeclamptic women.
AB  - OBJECTIVE: To determine the serum lipid profile, the activity of paraoxonase
      (PON, the lipophilic antioxidant component of HDL-cholesterol), and alterations
      of the arylesterase activity in preeclamptic women. STUDY DESIGN: This cross
      sectional study included 28 severe preeclamptic, and 24 healthy pregnant women.
      Fasting venous blood samples were collected during the antepartum period for
      spectrophotometric determination of the PON and arylesterase activities. RESULTS:
      In the severe preeclamptic group, the mean levels of total cholesterol,
      triglycerides, and LDL-cholesterol were 4, 5 and 9.8% higher, respectively, and
      HDL-cholesterol 9% lower than in the healthy controls. The PON and arylesterase
      activities were significantly lower in the severe preeclamptic women than in the
      controls, P<0.001 and P=0.000, respectively. A moderately positive correlation
      was detected between the serum levels of HDL-cholesterol and PON (r=0.49, P<0.02,
      n=52) and between HDL-cholesterol and arylesterase (r=0.42, P<0.05, n=52).
      CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased PON
      and arylesterase activities may have a role in pathogenesis of preeclampsia.

PMID- 15140513
TI  - Drug use by pregnant women and comparable non-pregnant women in The Netherlands
      with reference to the Australian classification system.
AB  - OBJECTIVE: To describe drug use in pregnancy, and compare drug use of pregnant
      women with non-pregnant women with respect to possible teratogenicity. STUDY
      DESIGN: A cross-sectional study based on pharmacy records from 1997 to 2001 was
      performed. Pregnant women and matched non-pregnant women (same physician and age)
      were identified. Prescriptions were set against the Australian risk
      classification. RESULTS: Thirty-five percent of all prescriptions for non
      pregnant women were safe in pregnancy (Australian classification A), in 14% the
      risk was unknown (B1, B2), 49% were potentially harmful drugs (B3, C, D, X), and
      in 3% no classification was available. For pregnant women these figures were 86,
      3, 10 and 2%, respectively. In non-pregnant women the highest percentages of
      prescriptions for unsafe drugs were for psycholeptics (99% not classified as
      safe), psychoanaleptics (100%), anti-inflammatory/antirheumetic products (100%),
      antihistamines (94%), antacids/anti-ulcer drugs (81%), antiepileptics (100%),
      beta-blockers (100%), systemic antimycotics (100%), antiprotozoals (97%),
      diuretics (100%) and immunosuppressives (100%). In pregnant women this pattern
      was comparable, except for antihistamines (22%) and antacids/anti-ulcer drugs
      (3%). CONCLUSION: We conclude that many drugs used by non-pregnant women should
      be avoided in pregnancy, and that pregnant women indeed do so. However, for some
      drug groups the available safe alternatives are limited.

PMID- 15140514
TI  - Decidualisation of cervical stromal cells.
AB  - OBJECTIVE: Control of cervical function is poorly understood. The major
      structural component of the cervix is collagen and peri-partum cervical changes
      are largely due to the action of collagenase, either released by resident cells
      or derived from an influx of neutrophils. More importantly, the cell type that
      initiates the changes in the cervix is unknown although the resident fibroblast
      is a possible contender. Little is known about the state of the cervical
      fibroblast during pregnancy. Decidualisation of the endometrium is essential for
      implantation and pregnancy. In man, pre-decidual and decidual transformation of
      endometrial stroma occurs under the influence of progesterone. Decidualisation
      can also be induced in vitro in endometrial fibroblast-like stromal cells where
      the process is also dependent on elevated intracellular cAMP levels. STUDY
      DESIGN: Cultured human cervical fibroblasts were treated with progestin
      (medroxyprogesterone acetate) and cAMP elevating agents for 6 and 10 days.
      RESULTS: After 6 days they expressed and released IGFBP-1 and prolactin (PRL) and
      underwent morphological changes by 10 days. In addition, there was an increase in
      progesterone receptor and prostaglandin E type 2 receptor mRNA (but not type 4).
      CONCLUSION: The propensity of cervical stromal cells to decidualise suggests that
      these differentiated cells may be a better model with which to study the
      initiation of labour.

PMID- 15140515
TI  - The association of progesterone, infant formula use and pacifier use with the
      return of menstruation in breastfeeding women: a prospective cohort study.
AB  - OBJECTIVES: This study sought to explore hormonal and postnatal factors, which
      are associated with the return of menstruation in breastfeeding mothers. DESIGN:
      A prospective cohort study in Bristol, UK. Ninety-one breastfeeding mothers of
      mixed parity were recruited at community-based antenatal clinics. Eighty-five
      mothers completed all stages and informed us about the return of menstruation.
      Data were collected from interviews and questionnaires antenatally, immediately
      postnatally, and 1 week, 4 weeks and 6 months later. Blood samples were taken at
      all time points except at 6 months. Associations between hormone levels,
      postnatal factors and the return of menstruation were explored using univariate
      and multivariate statistical survival analysis. RESULTS: Sixty-five (76%) mothers
      were still breastfeeding at 6 months and 46 (54%) of these were fully
      breastfeeding (not giving formula milk); 21 (32%) mothers started menstruating in
      the first 6 months whilst they were still breastfeeding and 14 were fully
      breastfeeding at 6 months. Survival analysis modelling showed that formula use
      (RR=4.27; 95% CI=1.89, 9.67), pacifier (dummy) use (RR=3.26; 95% CI=1.35, 7.84)
      and lower postnatal progesterone levels (P=0.006) each made a significant
      contribution to the chance of earlier resumption of menstruation. Prolactin and
      oestradiol levels showed no associations with the return of menstruation.
      CONCLUSIONS: Higher postnatal progesterone levels are associated with delayed
      menstruation; while the use of pacifiers and infant formula milk are associated
      with an earlier return to menstruation.

PMID- 15140516
TI  - Tubo-ovarian abscesses in postmenopausal women: gynecological malignancy until
      proven otherwise?
AB  - OBJECTIVE: To investigate the incidence of gynecological malignancy in menopausal
      women who develop tubo-ovarian abscesses (TOAs), and to address the differences
      in presentation and underlying pathology between premenopausal and postmenopausal
      women with TOAs. STUDY DESIGN: In a retrospective study we included 93 patients
      with a diagnosis of a TOA and compared a premenopausal group (group 1) with a
      postmenopausal group (group 2). RESULTS: Group 1 included 76 (82%), and group 2
      17 (18%) patients. Abdominal pain and pyrexia >38 degrees C were present in 93
      and 74% cases of group 1, and in 71 and 41% cases of group 2 (P=0.016 and 0.019,
      respectively). Irregular vaginal bleeding and gross ascites were significantly
      more frequent in group 2. With respect to benign additional pathology we found no
      differences between the two groups. On the contrary a significant association
      between TOAs in menopause and malignancy was established. In 8 (47%)
      postmenopausal cases a concomitant gynecological malignancy was found including a
      variety of cancers. CONCLUSION: Postmenopausal women presenting with TOAs, should
      be thoroughly investigated to exclude a concomitant pelvic malignancy.
      Conservative treatment of TOAs has no place during the menopause.

PMID- 15140517
TI  - p53 at codon 72 polymorphism, human papillomavirus infection and cervical
      lesions: a cross-sectional study from northeastern Italy.
AB  - OBJECTIVE: To test the hypothesis that p53 homozygous Arg/Arg genotype at codon
      72 is a significant risk factor for the development of HPV induced cervical
      cancer. STUDY DESIGN: A cross-sectional survey on p53 allelotypes distribution in
      women with different grade of cervical lesions and with or without HPV infection,
      in comparison to the distribution on a control group of women cytologically
      normal and HPV negative. RESULTS: No statistically significant difference in the
      p53 polymorphism distribution was found in relation to the infection with HPV,
      the cytological pattern and both conditions. A modest but constant over
      representation of Pro-allelotypes was found in all groups in comparison to the
      control group. CONCLUSION: Searching for p53 polymorphism in a clinical setting
      does not seem to support secondary prevention procedures, at least for women in
      this area.

PMID- 15140518
TI  - Psychometric properties of the Body Image Scale in women with benign
      gynaecological conditions.
AB  - OBJECTIVES: To evaluate the psychometric properties of the Body Image Scale
      (originally designed for use in cancer) in women with benign gynaecological
      conditions. STUDY DESIGN: Prospective completion of the Body Image Scale by women
      participating in the EVALUATE Hysterectomy Trial. The scale was completed pre
      operatively, then 6 weeks, 4 and 12 months post-operatively. The psychometric
      properties were evaluated by assessing the reliability, response prevalence,
      discriminant validity and sensitivity to change. Factor analysis was also
      conducted to determine the scale structure. RESULTS: The Body Image Scale showed
      good reliability and clinical validity. Differences between sub-groups of women
      were detected, demonstrating good discriminant validity. The Body Image Scale was
      shown to be responsive to changes in body image. CONCLUSIONS: The Body Image
      Scale was shown to be a reliable and valid tool for assessing body image in women
      with benign gynaecological conditions and for use in clinical trials involving
      such women.

PMID- 15140520
TI  - Post-therapy surveillance and after-care in ovarian cancer.
AB  - OBJECTIVES: Methods for surveillance of patients having completed primary cancer
      treatment are still not based on clinical studies, due to lack thereof. Therefore
      this study investigated how far surveillance as such, location of follow-up,
      method of detection, time of detection as well as early versus delayed start
      therapy for recurrence influences patients' overall survival. STUDY DESIGN: Seven
      hundred and four patient cases were retrospectively analyzed by chart review,
      each of whom had no evidence of tumor remaining after completion of primary
      cancer treatment. RESULTS: The aforementioned parameters had no significant
      influence on survival. Patients with late relapses showed significantly better
      chances of being cured by treatment for cancer recurrence (P<0.001). Patients
      profited significantly from successful treatment for recurrence (P<0.001).
      CONCLUSION: The study provided no evidence of intensive follow-up offering higher
      chances of survival. However, more intensive surveillance after a period of 2
      years may prove beneficial.

PMID- 15140519
TI  - Langerhans' cell count and HLA class II profile in cervical intraepithelial
      neoplasia in the presence or absence of HIV infection.
AB  - OBJECTIVES: The progression of immunosuppression in human immunodeficiency virus
      (HIV)+ women has been correlated with elevated incidence of squamous
      intraepithelial lesions (SIL), probably indicating the role of local immune
      milieu. In this study, we analysed S100, and HLA class II molecule expression in
      cervical biopsies according to HIV status, to the severity of SIL and to human
      papillomavirus (HPV) type. METHODS: Biopsies from 34 HIV+ and 44 HIV- patients
      with normal cervix or low- or high-grade SIL were studied. Langerhans' cells (LC)
      (S100), HLA class II and HLA-DQ molecules were evaluated by immunohistochemistry.
      HPV detection was performed using polymerase chain reaction (PCR). For
      statistical analysis Mann-Whitney (P< or =0.05) and Spearman test were used.
      RESULTS: Epithelial S100 and HLA class II density were significantly increased
      with the severity of lesion (P=0.032; P=0.005). Epithelial S100+ increased in
      HPV+ (P=0.038), and HLA class II density decreased in HPV 16+ (P=0.035) or 18+
      (P<0.0001) samples. HIV infection was associated with increased stromal S100+
      (P=0.0005) and decreased HLA class II densities (P=0.0001). Decreased stromal
      S100+ was observed in women with CD4<500 cells/microl (P=0.050). Among HIV+
      patients with SIL, the lowest S100 and epithelial HLA class II densities were
      detected in women with CD4<200 cells/microl (P=0.045). CONCLUSIONS: After the
      establishment of AIDS, increased numbers of immature LCs and a reduction in HLA
      class II occurred, possibly turning the cervical milieu more favourable to HPV
      persistence. HPV 16 and 18 infections may interfere with the antigen presenting
      activity, possibly as an evasion mechanism.

PMID- 15140521
TI  - Mesenteric vein thrombosis in a pregnant patient heterozygous for the factor V
      (1691 G --> A) Leiden mutation.
AB  - Factor V Leiden mutation is a risk factor for the development of thromboembolic
      events in pregnancy. Thrombosis of the mesenteric vein is a fairly infrequent
      condition complicating pregnancy. In this paper, we described a pregnant patient
      with mesenteric vein thrombosis who was heterozygous for the factor V Leiden
      mutation.

PMID- 15140522
TI  - Endotoxin-induced TNF-alpha production changes inversely to its plasma level
      during pregnancy.
AB  - OBJECTIVE: To study plasma TNF-alpha levels during normal pregnancy and the ex
      vivo endotoxin-induced TNF-alpha production of peripheral blood cells. STUDY
      DESIGN: In a longitudinal prospective study the ex vivo endotoxin-induced TNF
      alpha production of peripheral blood cells and the plasma level of TNF-alpha in
      18 women with uncomplicated pregnancies were determined at the 8th, 17th, 27th
      and 36th weeks of their pregnancy and 48 h and 6 weeks post-delivery. TNF-alpha
      levels were determined by ELISA technique. Data were analysed by Student's
      unpaired t-test. RESULTS: From the second trimester LPS-induced TNF-alpha
      production increased significantly (P<0.05) compared to non-pregnant values. In
      contrast, spontaneous TNF-alpha levels decreased with gestational age. Lowest
      values of plasma TNF-alpha levels and highest values of ex vivo endotoxin-induced
      TNF-alpha levels were detected at the 27th and 36th gestational weeks,
      respectively. Both parameters returned to non-pregnant levels after 6 weeks of
      delivery. CONCLUSION: Gestational age influences TNF-alpha production during
      normal pregnancy. The observed elevation of inducible TNF-alpha production may
      contribute to the immune defence of the mother against infections.

PMID- 15140523
TI  - T-helper 2-cytokine levels in women with threatened abortion.

PMID- 15140525
TI  - Rapid recurrence of endometrioma after transvaginal ultrasound-guided aspiration.

PMID- 15140526
TI  - Specialist life--Peter Husslein.

PMID- 15140527
TI  - Tirofiban for catheter intervention in acute myocardial infarction?

PMID- 15140528
TI  - Brugada sign: a normal variant or a bad omen? Insights for risk stratification
      and prognostication.

PMID- 15140529
TI  - Often seen but rarely recognised: cardiac complications of lamin A/C mutations.

PMID- 15140530
TI  - Imaging techniques for the assessment of myocardial hibernation. Report of a
      Study Group of the European Society of Cardiology.
AB  - This report of an ESC Study Group reviews current knowledge on myocardial
      hibernation and relevant imaging techniques, and provides an algorithm for
      investigation and management when a patient presents with ischaemic left
      ventricular dysfunction. It covers the definitions of myocardial viability,
      stunning and hibernation, it reviews the morphological findings in hibernation
      and it describes relevant clinical settings. The imaging and other techniques
      that are reviewed are electrocardiography, positron-emitting and single photon
      emitting scintigraphic imaging, echocardiography, radionuclide angiocardiography,
      magnetic resonance imaging, X-ray transmission tomography, invasive X-ray
      angiocardiography and electromechanical mapping. The evidence for the techniques
      to predict improvement of regional and global function after revascularisation is
      summarised and patient symptoms and clinical outcome are also considered. Each
      technique is classified in its ability to assess myocardial viability, function
      and perfusion and also for their roles in the assessment of the patient with
      ischaemic left ventricular dysfunction who is asymptomatic or who has angina or
      heart failure. A simplified clinical algorithm describes the initial assessment
      of left ventricular function, then viability and then perfusion reserve allowing
      regions of myocardium to be characterised as transmural scar, intramural scar,
      hibernation or ischaemia.

PMID- 15140532
TI  - Influence of isoprostane F2alpha-III on reflow after myocardial infarction.
AB  - AIMS: To investigate whether the vasoconstrictor isoprostane F2alpha-III
      (iPF2alpha-III), released during myocardial reperfusion, contributes to the
      low/no reflow phenomenon observed following acute myocardial infarction (AMI).
      METHODS AND RESULTS: Thirteen patients undergoing primary percutaneous coronary
      intervention (PCI) for AMI had iPF2alpha-III measured by high-performance liquid
      and gas chromatography-mass spectrometry. Isoprostane F2alpha-III concentrations
      were significantly higher following PCI than in controls (1.5+/-1.3 vs.16+/-0.06
      nM, p < 0.001). Mean iPF2alpha-III concentration correlated positively with ST
      segment resolution at 90 min (R = 0.62, p < 0.05). In the isolated murine heart:
      (a) coronary vasoconstriction occurred at, or above, iPF2alpha-III concentrations
      of 1 microM. From 1 to 10 microM, iPF2alpha-III induced dose-dependent
      vasoconstriction (p = 0.005) with reduction in coronary flows (f) of 57+/-5% and
      31+/-4% (percentage baseline), respectively; (b) SQ29548 1 microM completely
      reversed the vasoconstrictive effects of iPF2alpha-III 10 microM; (c) SQ29548 1
      microM infused during reperfusion following 30 min ischaemia had no effect on CF
      or infarct volume. CONCLUSION: Concentrations of iPF2alpha-III released into the
      venous circulation during reperfusion following AMI in humans are significantly
      lower than those required to diminish coronary flow in the murine heart;
      increased levels indicate successful reperfusion. Inhibition of iPF2alpha-III has
      no effect on coronary flow or infarct size in the murine heart, suggesting that
      iPF2alpha-III alone does not account for the low/no reflow phenomenon observed
      following AMI.

PMID- 15140531
TI  - Facilitation of primary coronary angioplasty by early start of a glycoprotein
      2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction
      evaluation (On-TIME) trial.
AB  - AIM: Although primary angioplasty is effective despite additional transportation
      delay, improved patency before PCI might be obtained by starting pharmacological
      pre-treatment before transportation. METHODS AND RESULTS: From June 2001 to
      November 2002, 507 patients with acute myocardial infarction, who were
      transferred to a PCI centre, were randomised to early, pre-hospital initiation of
      Tirofiban (Early) or to initiation in the catheterisation laboratory (Late). The
      primary end-point was TIMI flow grade 3 of the infarct-related vessel (IRV) at
      initial angiography, as assessed by an independent core-lab. The effect of
      Tirofiban on each TIMI flow component, the presence of thrombus at initial
      angiography and pre-PCI myocardial blush grade were secondary end-points. A large
      proportion of patients (41%) was diagnosed and randomised in the ambulance,
      without intervention of a physician. In the Early group, Tirofiban was
      administered a median of 59 min (range 11-178 min) earlier than in the Late
      group. At initial angiography, TIMI 3 flow was present in 19% the Early group and
      in 15% in the Late group (P = 0.22). The combined incidence of TIMI 2 or 3 flow
      was present in 43% in the Early group and in 34% in the Late group, respectively
      (P = 0.04). Thrombus or a fresh occlusion was present in 60% and 73% in the Early
      and Late group, respectively (P = 0.002). A pre-PCI myocardial blush grades 2 or
      3 was more often present in the Early group (30% vs. 22%, P = 0.04). However, no
      difference in TIMI 3 flow or myocardial blush grade was found between the groups,
      post-PCI. At one-year follow-up, the combined incidence of death or recurrent MI
      was not different between the groups (7.0% vs. 7.0%, P = 0.99). CONCLUSION: Early
      initiation of Tirofiban did not improve initial TIMI 3 flow of the IRV
      significantly. Despite a better patency (TIMI 2 or 3 flow), a lower prevalence of
      thrombus or fresh occlusion and a better myocardial perfusion in the infarct
      related region pre-PCI, no beneficial effect on post-PCI angiographic or clinical
      outcome was found, as compared to initiation of Tirofiban in the catheterisation
      laboratory.

PMID- 15140533
TI  - Role of collateral circulation in the acute phase of ST-segment-elevation
      myocardial infarction treated with primary coronary intervention.
AB  - AIMS: The role of collateral flow in the first hours of infarction remains
      unclear. Our aim was to determine whether the presence of coronary collateral
      flow, as evidenced by angiography, has a beneficial effect on infarct size and
      left ventricular function in acute myocardial infarction (MI) treated by means of
      early percutaneous coronary intervention (PCI). METHODS: Between 1994 and 2001,
      1059 patients with acute MI treated with primary PCI, TIMI (Thrombolysis in
      Myocardial Infarction) 0 or 1 flow at first contrast injection and technically
      adequate angiograms for collateral flow detection were analysed. RESULTS:
      Comparison of collateral flow grades 0, 1, and 2/3 showed that increased
      collateral flow was associated with a lower incidence of Killip class >/= 2 at
      presentation (12% vs. 10% vs. 3%, p for trend 0.02), less need for intra-aortic
      balloon pumping after PCI (17% vs. 13% vs. 5%, p for trend 0.005), better
      myocardial blush grade (MBG) in infarcts related with the left anterior
      descending coronary artery (LAD) (MBG3: 14% vs. 18% vs. 34%, p for trend 0.01),
      and smaller enzymatic infarct size (cumulative lactate dehydrogenase release 36 h
      after symptom onset [LDHQ(36)]) (1932+/-1531 U/l vs. 1870+/-1458 U/l vs. 1217+/
      762 U/l, p for trend 0.041). These beneficial effects were particularly evident
      in LAD-related infarcts. CONCLUSION: The presence of angiographically detectable
      collaterals has a protective effect on enzymatic infarct size and pre- and
      postintervention haemodynamic conditions in patients with acute MI treated by
      primary PCI, in particular when Rentrop grade 2/3 is present and the LAD is
      involved in the infarct.

PMID- 15140534
TI  - Relative value of N-terminal probrain natriuretic peptide, TIMI risk score,
      ACC/AHA prognostic classification and other risk markers in patients with non-ST
      elevation acute coronary syndromes.
AB  - AIMS: We prospectively studied the additive value of N-terminal probrain
      natriuretic peptide (NT-proBNP) in relation to the Thrombolysis in Myocardial
      Infarction (TIMI) risk score and the American College of Cardiology/American
      Heart Association (ACC/AHA) joint prognostic classification, and compared the
      predictive capacity of NT-proBNP, troponin T (TnT), C-reactive protein (hsCRP),
      myoglobin, and creatine kinase-MB (CK-MB) concentrations in a cohort of 1483
      consecutive patients with non-ST-segment-elevation acute coronary syndromes (NSTE
      ACS). METHODS AND RESULTS: Centralised measurements of NT-proBNP, TnT, myoglobin,
      and hsCRP were performed 3 h (median) after admission. Adjusting by clinical, ECG
      variables, and biomarkers, NT-proBNP concentration was the strongest independent
      predictor of in-hospital (OR 1.7, 95% CI: 1.31-2.20, p < .001) and 180-day
      mortality (OR 1.67, 95% CI: 1.41-1.99, p < .001), and added significant
      prognostic information to the TIMI and ACC/AHA prognostic categories. NT-proBNP
      was not an independent predictor of risk of new myocardial infarction, even in
      the acute or long term. CONCLUSIONS: In NSTE-ACS, NT-proBNP adds substantial
      information to the TIMI risk score and the ACC/AHA classification. Compared to
      other biomarkers, NT-proBNP is the strongest independent predictor of in-hospital
      and 180-day mortality.

PMID- 15140535
TI  - Chronic psychosocial stress predicts long-term cardiovascular morbidity and
      mortality in middle-aged men.
AB  - AIMS: To prospectively investigate the association between self-reported
      psychosocial stress and long-term cardiovascular (CV) morbidity and mortality in
      a population-based cohort. METHODS AND RESULTS: The Malmo Preventive Project is a
      population-based screening and intervention programme for cardiovascular disease
      (CVD) risk factors. Between 1974 and 1980, a total of 13,609 (2741 women)
      individuals, mean age 45 years, had self-reported chronic stress determined by
      questionnaire. CV morbidity and mortality were followed up in national
      registries. Median follow-up time was 21 years. The risk ratio (RR) for a fatal
      or nonfatal CV incident in the men and women of the group reporting chronic
      stress was 1.27 (95% CI 1.15-1.39). After stepwise adjustments for known CV risk
      factors, the RR was reduced to 1.14 (1.02-1.28). The highest RR was found for
      fatal stroke in men reporting chronic stress, 2.04 (1.07-3.88). For women alone,
      there was no significant increase in risk after adjustments. CONCLUSION: Self
      reported chronic stress is an independent risk factor for CVD, particularly fatal
      stroke, in middle-aged men; it continues to be a risk factor after adjustment for
      several other known risk factors. The adjustment itself might reflect mechanisms
      whereby psychosocial stress directly or indirectly exerts its effects on the
      body, indicating a possible over-adjustment.

PMID- 15140536
TI  - Prevalence and prognosis of subjects with Brugada-type ECG pattern in a young and
      middle-aged Finnish population.
AB  - AIMS: The purpose of this study was (1) to determine the prevalence of Brugada
      syndrome ECG abnormalities ("Brugada sign") in two Finnish populations and (2) to
      evaluate the natural course of subjects with the "Brugada sign". METHODS AND
      RESULTS: The study population consisted of 2479 healthy male Air Force applicants
      (age 18-30 years), and 542 healthy middle-aged subjects (age 40-60 years). All
      subjects underwent a thorough physical examination and 12-lead ECG in 1980-1990
      (first population) and in 1991-1992 (second population). The ECG criteria
      suggested by the European Society of Cardiology were used to identify subjects
      with the "Brugada sign". Fifteen (0.61%) subjects in the first population and
      three subjects in the second population (0.55%) fulfilled the ECG criteria for
      type 2 or 3 Brugada syndrome, i.e., they had J-point elevation and a saddleback
      type ST-segment configuration in the right precordial leads. Type 1 Brugada ECG
      abnormality (coved ST-segment elevation) was not seen in any subject. No
      mortality or life-threatening ventricular arrhythmias occurred in either study
      population during follow-up (19+/-2 years and 11+/-1 years, respectively).
      CONCLUSION: The benign natural course of the patients with the "Brugada sign"
      suggests that in asymptomatic subjects without a family history of sudden cardiac
      death, type 2 or 3 Brugada ECG pattern is a normal variant rather than a specific
      predictor of life-threatening ventricular arrhythmias.

PMID- 15140537
TI  - Incidence, clinical implications and prognosis of atrial arrhythmias in Brugada
      syndrome.
AB  - AIMS: This single-centre prospective study was designed to determine the
      incidence, therapeutic implications and prognosis of atrial arrhythmias (AA) in
      patients with Brugada syndrome (BS). METHODS AND RESULTS: Fifty nine consecutive
      patients with BS and 31 age and gender-matched controls underwent an
      electrophysiological exploration and were followed-up during 34+/-13 months. The
      final AA incidence was 20% in BS patients vs 0% in controls (p < 0.01).
      Ventricular inducibility was significantly related to a history of AA (p = 0.02).
      The incidence of AA in patients with a spontaneous electrocardiogram of BS was
      26% vs 10% in patients with a flecainide-induced electrocardiogram (p < 0.05). In
      patients with an indication of implantable cardioverter defibrillator (ICD), the
      incidence of AA reached 27% vs 13% in patients with BS but without ICD indication
      (p < 0.05). Inappropriate shocks due to AA episodes were observed in 14% of ICD
      patients vs 10.5% of appropriate shocks. Multivariate analysis identified the
      implantation of a single-chamber device as an independent predictive factor of
      inappropriate ICD discharges (p < 0.05). CONCLUSION: BS patients exhibit an
      abnormally high proportion of AA. Our data strongly suggest a more advanced
      disease process in BS patients with spontaneous AA. Careful programming of single
      chamber ICD should be recommended to avoid inappropriate discharges.

PMID- 15140538
TI  - A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients
      with familial dilated cardiomyopathy.
AB  - AIMS: The mutations most frequently associated with dilated cardiomyopathy (DCM)
      have been reported in the lamin A/C gene. The role of variants of the lamin A/C
      gene was investigated in patients with DCM from eastern and southern Finland.
      METHODS AND RESULTS: All 12 exons of the lamin A/C gene were screened in 18 well
      characterised familial DCM patients from eastern and southern Finland and in 72
      sporadic DCM patients from eastern Finland using the PCR-SSCP method. A novel
      mutation, Ser143Pro (S143P), was detected in the lamin A/C gene in 24 subjects
      from 5 unrelated families and in one sporadic case of DCM. Sinus or
      atrioventricular nodal dysfunction occurred in the majority of the affected
      subjects, many of which required pacemaker implantation. Seven patients (28%)
      with the S143P mutation died suddenly or from progressive heart failure, or
      underwent heart transplantation. The haplotypes 5-5-5-3, 5-5-5-2, and 5-5-5-1 co
      segregated with the Ser143Pro mutation, suggesting a founder effect of this
      mutation. CONCLUSIONS: A novel mutation S143P in the lamin A/C gene was found to
      be common among Finnish DCM patients. Haplotype analysis strongly suggests a
      founder effect of this mutation. The phenotype is characterised by severe heart
      failure, progressive atrioventricular conduction defects, and sudden death.
      Screening for the lamin A/C gene and, particularly, the S143P mutation seems
      warranted when patients with DCM have conduction system disturbances.

PMID- 15140539
TI  - Effect of carbonic anhydrase-related protein VIII expression on lung
      adenocarcinoma cell growth.
AB  - Carbonic anhydrase-related protein VIII (CA-RP VIII) is expressed in most non
      small cell lung cancer, and especially strongly at the front of tumor
      progression. Screening analysis of CA-RP VIII expression in a panel of cultured
      lung cancer cell lines showed that a well differentiated adenocarcinoma cell
      line, PC-9, appeared to lack CA-RP VIII. Subsequently, CA8 cDNA was transfected
      with an expression vector into PC-9. Ectopic overexpression of CA-RP VIII reduced
      the growth of PC-9 cells on uncoated culture dishes, especially when the cultures
      were started at low cell density, but increased cell growth on laminin-coated
      dishes. Interestingly, ectopic CA-RP VIII expression markedly reduced caspase-3
      activity induced by serum starvation and anti-cancer agents in PC-9 cells. The
      present findings suggest that CA-RP VIII expression promotes progression of lung
      cancer by multifarious mechanisms.

PMID- 15140541
TI  - The effect of smoking status on survival following radiation therapy for non
      small cell lung cancer.
AB  - The dangers of cigarette smoking are numerous and well-known, including the
      causal relationship to lung cancer. This study investigates the effect that
      smoking status at initial consultation has on radiation therapy for non-small
      cell lung cancer (NSCLC). We identified 237 patients treated between 1991 and
      2001 with definitive radiation or chemoradiation who had complete smoking
      histories. Median age was 73, with 56% males. Distribution by stage was as
      follows: I/II-27%, IIIA-27%, IIIB-45%, recurrent-1%. Two-year overall survival,
      stratified by stage of disease, was calculated from the time of initiation of
      treatment. Median follow-up time from the end of treatment was 13 months. Among
      those with stage I/II disease, current smokers had a 2-year survival rate of 41%
      and a median survival of 13.7 months while non-smokers had a 2-year survival of
      56% and a median survival of 27.9 months (P = 0.01). Patients with stage III
      disease did not show any significant differences in overall survival. There were
      no significant differences in cancer-specific survival in either stage. In
      conclusion, among NSCLC patients diagnosed with early stage disease, current
      smokers have a poorer prognosis for survival after radiation therapy.

PMID- 15140540
TI  - Lack of association between Caucasian lung cancer risk and O6-methylguanine-DNA
      methyltransferase-codon 178 genetic polymorphism.
AB  - The formation of DNA adducts is thought to be a critical step for the induction
      of chemically induced cancer. O(6)-Methylguanine-DNA methyltransferase (MGMT) is
      a ubiquitously expressed enzyme that repairs DNA adducts formed by alkylating
      carcinogens. Thus, genetic polymorphisms of the MGMT that could result in
      differences in MGMT activity are potential risk factors for cancer. In the
      present study, we established a convenient and reliable genotyping method for the
      MGMT codon 178 polymorphism, a Lys (AAG) to Arg (AGG) substitution, using
      restriction fragment length polymorphism (RFLP), and studied differences in the
      distribution of this polymorphism in 92 Caucasian lung cancer patients and 85
      controls. Frequencies of the "A" and "G" alleles (MGMT codon 178, AAG and AGG,
      respectively) were 0.91 and 0.09, respectively. The genetic polymorphism of the
      MGMT codon 178 was linked with that of the MGMT codon 143 (P < 0.05). The
      distribution of the MGMT codon 178 genetic polymorphism was not significantly
      different between lung cancer patients and controls. Thus, our study suggests
      that the MGMT codon 178 (and possibly 143) polymorphisms do not appear to
      markedly affect lung cancer risk for this population. In addition, we found an
      apparent 10bp-deletion in the intron before exon 5 by DNA sequencing. Because
      this "deletion" was observed in all sequenced samples (N = 20), the previously
      reported human (Caucasian) MGMT gene sequence should be revised to exclude this
      10bp segment.

PMID- 15140542
TI  - Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the
      diagnostic biopsies and the corresponding resected tumors in non-small cell lung
      cancer.
AB  - Substaging using molecular markers has been proposed to try to identify
      prognostic factors allowing to define groups of patients with lung cancer for
      whom specific therapy might be of benefit. The pre-operative assessment of these
      markers seems to be important specially in case of neoadjuvant chemotherapy. The
      aim of our study was to compare the expression of two potential prognostic
      factors (p53 and Ki-67) and two potential therapeutic targets (EGF-R and c-erbB
      2) assessed on biopsy samples (B) of non-small cell lung cancer (NSCLC) with that
      of the corresponding resected tumor (RT). The expression of these biological
      markers was evaluated by immunohistochemistry on B and on the paired RT in 28
      patients. The mean percentage of p53 positive cells was 28% in RT and 38% in B
      with 81% CR between B and RT and 19% FP on B. Considering RT results as standard,
      the positive (PPV) and negative predictive value (NPV) of the B were,
      respectively, 74 and 100%. The mean percentage of EGF-R positive cells was 11% in
      RT and 28% in B. With a cut-off of 1%, we found 85% concordant results (CR)
      between B and RT, 4% false negative (FN) and 11% false positive (FP) on B. The
      PPV and NPV values of the B were, respectively, 80 and 92%. The 8% B and 19% RT
      were considered as positive for c-erbB-2. We found 15% FN and 4% FP on B with 81%
      CR between B and RT for c-erbB-2. The NPV of the B was 83%. The mean percentage
      of Ki-67 positive cells was 32% in RT and 14% in B. We found 82% CR between B and
      RT, 14% FN and 4% FP on B. The PPV of the B was 96%. In conclusion, biopsies may
      provide reliable information about p53, EGF-R, c-erbB-2 and Ki-67 in lung
      carcinoma and could help to elaborate a therapeutic strategy.

PMID- 15140543
TI  - Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small
      cell lung cancer patients.
AB  - The present study was designed to investigate whether a correlation exists
      between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or
      fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients.
      One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8,
      adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary
      disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group
      65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results
      obtained showed that median D-dimer levels were higher in NSCLC patients (3.0
      microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls
      (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in
      26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On
      the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and
      21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc
      levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l)
      patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels
      were significantly associated to positive TNF-alpha levels in patients without
      distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were
      independently related to the presence of positive D-dimer levels in patients with
      non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha
      might be responsible for an activation of fibrinolysis in patients with NSCLC.

PMID- 15140544
TI  - Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell
      lung cancer patients treated with cisplatin combination chemotherapy.
AB  - ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision
      repair cross-complementation group 2) as genes have been known to be belonged to
      the nucleotide excision repair pathway and therefore related to DNA repair.
      Polymorphisms in these genes have been rarely evaluated in terms of predicting
      cancer patient survival. We investigated whether these polymorphisms have an
      effect on response to chemotherapy and survival in 109 patients with non-small
      cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms
      of ERCC1 Asn118Asn (C --> T), XPD Lys751Gln (A --> C) and Asp312Asn (G --> A)
      were evaluated using a SNaPshot kit. As for chemotherapy response, treatment
      response did not show statistically significant differences between the wild
      genotypes and the variant genotypes for the ERCC1 and XPD gene. The median
      survival time of all patients was 376 days (95% CI, 291-488). As for survival
      rate according to the polymorphism of codon 118 in ERCC1, median survival time in
      patients showing C/C genotype was 486 days (95% CI, 333-x), which was
      significantly different from the 281 days (95% CI, 214-376) of patients with the
      variant genotype (T/T or C/T) (P = 0.0058). Using the Cox-proportional hazards
      model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight
      loss and performance status effected overall survival significantly (P = 0.0001,
      0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751
      and 312 in the XPD gene did not affect patient survival (P = 0.4711 and 0.4542,
      respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1
      is a surrogate marker for predicting better survival in non-small-cell lung
      cancer patients treated with cisplatin combination chemotherapy.

PMID- 15140545
TI  - Comparison of whole-body FDG-PET to bone scan for detection of bone metastases in
      patients with a new diagnosis of lung cancer.
AB  - The purpose of this study was to compare the accuracy and agreement of whole-body
      positron-emission tomography (PET) scan to bone scintigraphy for the detection of
      bony metastases in staging patients with newly diagnosed lung cancer. The tumor
      registry and nuclear medicine database at our institution were queried and
      identified all patients between July 1998 and August 2002 with a new diagnosis of
      lung cancer, a whole-body 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET scan, and a
      bone scan prior to therapy. All of these patients' radiologic reports were then
      retrospectively reviewed, and confirmation of bone metastases was determined by
      consideration of all available clinical information. The sensitivity,
      specificity, and accuracy for each study were then calculated. Two hundred and
      fifty-seven patients fulfilled the entrance criteria. One hundred and four
      patients (40%) presented with stage IV disease, and bone metastases were
      confirmed in 57 (22%) patients. The accuracies of PET and bone scan were 94 and
      85% (P < 0.05), sensitivity values were 91 and 75%, and specificity values were
      96 and 95%, respectively. The weighted-kappa statistic suggested moderate
      agreement between the two modalities KW = 0.510, 95% CI, 0.402-0.618). The use of
      both whole-body PET and bone scintigraphy as initial staging studies in lung
      cancer patients provides redundant information about the presence of bony
      metastases. The improvement in accuracy and sensitivity with PET suggests bone
      scan can be eliminated from the staging evaluation at presentation. Due to its
      retrospective nature, the results of this study are subject to several forms of
      bias including selection bias, verification bias, test review bias, and
      incorporation bias. A prospective trial with appropriate verification of bony
      metastases is suggested to confirm the results.

PMID- 15140546
TI  - Surgical lung cancer. Risk operative analysis.
AB  - STUDY OBJECTIVE: To identify those variables that are associated with operative
      morbidity or mortality in cases of thoracotomy in lung cancer. SETTING: Third
      level university hospital. PATIENTS: Consecutive patients with thoracotomy due to
      lung cancer operated on between 1994 and 1997 (n = 115). METHODS: Pre- and
      postoperative variables potentially associated with operative morbidity or
      mortality were retrieved prospectively as follows: demographic and clinical
      characteristics of the patients, cardiopulmonary function characteristics, tumour
      characteristics, and treatment characteristics. A bivariate analysis of all
      variables under evaluation was carried out in order to identify those variables
      associated with operative morbidity and mortality. A multivariable analysis of
      the selected variables was then conducted using a logistic model. RESULTS: The
      predicted postoperative product (predicted FEV1 x predicting diffusing capacity
      of carbon monoxide), the carbon monoxide diffusion coefficient (Kco) and the
      contralateral pulmonary perfusion are variables that relate to the overall
      morbidity or mortality (number of events 63, 55%) (-2 log likelihood chi2 = 22.9;
      R2 = 0.27). For variables associated with postoperative morbidity, the best
      associative model combines functional variables (diffusion, predicted FEV1),
      endoscopic variables (obstructed segments to be resected), clinical variables
      (comorbidity) and an important postoperative variable, the pathological tumoural
      staging (pN) (number of events 49, 43%) (-2 log likelihood chi2 = 32.9; R2 =
      0.36). CONCLUSION: The numerous variables under analysis are poorly associated
      with morbidity or mortality after thoracotomy in lung cancer. With regard to
      postoperative morbidity, the best associative models combine information that is
      known pre- and postoperatively and which is provided by both the patient and the
      tumour.

PMID- 15140547
TI  - Results of superior vena cava resection for lung cancer. Analysis of prognostic
      factors.
AB  - AIMS: The benefits of superior vena cava (SVC) resection for lung cancer remain
      controversial. Data obtained in four international centers were analyzed in order
      to identify prognostic factors and thus guide in future patient selection.
      MATERIALS AND METHODS: Retrospective study. Prognostic factors were examined by
      logistic regression for postoperative morbidity/mortality using the Kaplan-Meier
      method (log rank test) and the Cox proportional-hazard model for survival.
      RESULTS: From 1963 to 2000, 109 patients underwent SVC resection. Induction
      treatment was given to 23 (21%) patients. The SVC was resected for T involvement
      in 78 (72%) cases and for N involvement in 31 (28%) cases. Fifty-five (50.5%)
      patients underwent pneumonectomy (20 with carinal resection), while the remaining
      underwent lobar resections. Prosthetic SVC replacement was performed in 28 (26%)
      patients; partial resection with running suture (53%), vascular stapler (13%), or
      patch (7%) was performed in 80 patients; 1 patient did not undergo
      reconstruction. Pathological examination identified direct involvement (T4) in 66
      (60%) patients and N2 disease in 55 (50%) patients. Major postoperative morbidity
      and mortality were 30 and 12%, respectively. Median intensive care unit stay was
      3 days, while median hospital stay was 16 days. Five-year survival was at 21%,
      with median survival at 11 months. In multiple regression analysis, induction
      treatment was associated with an increased risk of major complications (P =
      0.016). None of the factors assessed demonstrated an association with
      postoperative death. In multivariate survival analysis, both pneumonectomy and
      complete resection of the SVC with prosthetic replacement were associated with a
      significant increased risk of death (P = 0.0013 and 0.014, respectively).
      CONCLUSIONS: The radical resection of lung cancer involving the SVC may result in
      a permanent cure in carefully selected patients. The type of pulmonary resection
      (i.e., pneumonectomy) and the type of SVC resection (i.e., complete resection
      with prosthetic replacement) are the prognostic factors with the greatest adverse
      effect on survival.

PMID- 15140548
TI  - Phase II study of oral etoposide and intravenous paclitaxel in extensive-stage
      small cell lung cancer.
AB  - BACKGROUND: This study evaluated the activity and tolerance for the combination
      of oral etoposide and paclitaxel as first-line therapy for patients with
      extensive SCLC. METHODS: A total of 57 patients were enrolled in this study. A
      cycle of chemotherapy consisted of oral etoposide administered as 50 mg BID on
      days 1 through 10 and paclitaxel administered as 150 mg/m(2) IV (3 h infusion)
      along with the first dose of etoposide on day 10. Patients were assessed for
      response to therapy (regression, stable disease, progression), survival, time to
      disease progression, and toxicity. RESULTS/CONCLUSIONS: Fifty-five patients were
      evaluable for efficacy parameters. Among the 55 patients, there were six with
      complete regression of disease, 18 with partial regression, 11 with regression,
      five with stable disease, and 15 with progressive disease, yielding an overall
      response rate of 63.6% (95% confidence interval, 50.0-76.0%). The 6-month and 1
      year progression-free survival rates were 48.2 and 18.9%, respectively. The
      median time to disease progression was 5.8 months. The overall survival rates
      were 67.3% at 6 months and 41.8% at 1 year. The combination of oral etoposide and
      paclitaxel demonstrated significant efficacy as first-line therapy for extensive
      SCLC, with an overall response rate of 63.6% for 55 evaluable patients. In
      addition, the treatment was well tolerated with no unexpected toxicities.

PMID- 15140549
TI  - Phase II study of carboplatin and weekly paclitaxel combination chemotherapy in
      advanced non-small cell lung cancer: a Kansai Clinical Oncology Group study.
AB  - The objective of this phase II study was to evaluate the efficacy and toxicity of
      carboplatin and weekly paclitaxel combination chemotherapy in previously
      untreated, advanced non-small cell lung cancer (NSCLC). Patients received
      paclitaxel at a dose of 70 mg/m(2) on days 1, 8, 15, and carboplatin with the
      target dose of area under the curve (AUC) of 6 on day 1 every 28 days. Forty-six
      patients were enrolled. A median of four cycles (range, 1-13) were administered.
      Complete response was observed in one patient (2.2%) and partial response in 23
      patients (50%), yielding an overall intent-to-treat response rate of 52.2% (95%
      confidence interval, 37.8-66.6%). The median survival time was 395 days and 1
      year survival rate was 51.4%. Toxicities were mild. Twelve patients (26%) had
      grade 3 and three patients (7%) had grade 4 neutropenia. Grade 3 thrombocytopenia
      was seen in four patients (8%). Massive hematoemesis due to duodenal ulcer was
      observed in one patient, but no other patients experienced grade 3 or more non
      hematological toxicities. There was no treatment-related death. Carboplatin and
      weekly paclitaxel combination chemotherapy is an efficacious and feasible regimen
      in patients with advanced NSCLC, and this treatment will be a reasonable
      alternative to the conventional triweekly regimen of paclitaxel and carboplatin.

PMID- 15140550
TI  - High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in
      patients with non-small cell lung cancer: results of a dose-finding study.
AB  - PURPOSE: To determine the maximum tolerated doses (MTD) and the dose-limiting
      toxicities (DLTs) of the weekly administration of docetaxel and gemcitabine as
      first-line treatment in patients with advanced non-small cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with histologically or
      cytologically confirmed unresectable stage III(B) or IV NSCLC were enrolled onto
      the study. Escalated doses of gemcitabine (starting dose 700 mg/m(2) per week)
      and docetaxel (starting dose 30 mg/m(2) per week) were given on a weekly basis
      for three consecutive weeks in cycles of 4 weeks. RESULTS: Twenty-six patients
      received a total of 94 chemotherapy cycles. At the doses of docetaxel 40 mg/m(2)
      per week and gemcitabine 1000 mg/m(2) per week, the MTD had not yet been reached.
      However, the study was prematurely closed because of a high incidence of severe
      pulmonary adverse events. Six (23%) patients developed fever and pulmonary
      dysfunction (severe dyspnea, hypoxia in association with diffuse interstitial
      pneumonitis), which was fatal in two of them. No risk factors were identified
      contributing to these pulmonary adverse events; four patients had a low absolute
      number of peripheral blood CD4+ lymphocytes. Grade 3/4 neutropenia occurred in
      five (19%) patients and grade 3/4 anemia in two (8%). CONCLUSION: The weekly
      administration of gemcitabine and docetaxel in patients with advanced NSCLC is
      associated with a high incidence of severe pulmonary toxicity, which does not
      seem to be dose-related. The regimen cannot be used outside a clinical protocol.

PMID- 15140551
TI  - Phase II study of a multidisciplinary approach with induction chemotherapy,
      followed by surgical resection, radiation therapy, and consolidation chemotherapy
      for unresectable malignant thymomas: final report.
AB  - PURPOSE: To evaluate tumor resectability after induction chemotherapy and to
      determine disease-free and overall survival rates of patients with locally
      advanced unresectable thymoma that received a multimodal treatment regimen.
      PATIENTS AND METHODS: Twenty-two patients (9 men, 13 women) with histologically
      confirmed invasive thymoma were treated with a multidisciplinary regimen
      consisting of three courses of induction chemotherapy, surgical resection, and
      radiation therapy, followed by three courses of consolidation chemotherapy. The
      median age was 47 years (range, 25-70). Eleven patients had stage III disease, 10
      patients, stage IVA, and one patient, IVB. The most common histologic type was
      lymphocytic. Induction chemotherapy consisted of 500 mg/m(2) of cyclophosphamide
      on day 1; doxorubicin (20 mg/m(2) per day) on days 1-3 via continuous infusion (a
      total of 60 mg/m(2)); cisplatin (30 mg/m(2) per day) on days 1-3 (a total of 90
      mg/m(2)); and prednisone (100 mg per day) on days 1-5. This cycle was repeated
      three times at 3-4-week intervals. Patients then underwent surgery for tumor
      resection and received radiotherapy. Consolidation chemotherapy given at 80% of
      the induction chemotherapy doses of cyclophosphamide, doxorubicin, and cisplatin
      and 100% of the dose of prednisone was then repeated every 3-4 weeks for a total
      of three courses. RESULTS: Induction chemotherapy produced major responses in 17
      (77%) of the 22 patients including 3 (14%) complete responses (CR) and 14 (63%)
      partial responses (PR). Twenty-one patients underwent surgical exploration: 16
      (76%) had complete resection and 5 (24%) had incomplete resection; one patient
      refused surgery. All 22 patients received radiation therapy. Nineteen of 22
      patients completed the planned therapy, and all but one had completed
      consolidation chemotherapy at the time of analysis. With a median follow-up time
      of 50.3 months, 18 of the 19 patients who completed the multidisciplinary
      approach were disease-free. Of the 22 patients originally registered, 20 were
      alive at the time of analysis (one patient died of endocarditis, and one died of
      recurrent disease). The overall survival rate was 95% at 5 years (95% confidence
      interval (CI), 0.87-1.0) and 79% at 7 years (95% CI, 0.55-1.0). The progression
      free survival rates were 77% at 5 years (95% CI, 0.58-1.0) and 77% at 7 years
      (95% CI, 0.58-1.0). The major side effect from induction and consolidation
      chemotherapy was myelosuppression. Nine patients experienced grade III/IV
      neutropenia, which included neutropenic fever in two patients, and grade III
      thrombocytopenia in two patients. The most common nonhematologic side effects
      were fatigue, nausea and vomiting, and decreased appetite. One patient
      experienced acute respiratory distress syndrome after surgical resection and
      required a prolonged hospitalization. No patients developed cardiac toxic
      effects, and no surgical mortality occurred. CONCLUSIONS: The use of induction
      chemotherapy to optimize surgical resectability of thymoma followed by radiation
      therapy and consolidation chemotherapy lead to good control of residual disease
      and high overall survival rates. We believe that this combined multidisciplinary
      approach prolongs lives and may cure locally advanced unresectable malignant
      thymomas. Future prospective multi-institutional studies are needed to further
      verify or define the best treatment for this patient population.

PMID- 15140552
TI  - Neutropenic enterocolitis (typhilitis) associated with docetaxel therapy in a
      patient with non-small-cell lung cancer: case report and review of literature.
AB  - Neutropenic enterocolitis (NE) is an unusual acute complication of neutropenia,
      most often associated with leukemia and lymphoma which is characterized by
      segmental cecal and ascending colon ulceration that may progress to necrosis,
      perforation, and septicemia. We present a case of neutropenic enterocolitis in a
      patient with non-small-cell lung cancer who received docetaxel and flavopiridol
      as part of a phase I clinical trial and review cases in the literature where
      docetaxel was involved. Given the increased use of docetaxel and other taxanes in
      the treatment of advanced lung cancer, physicians should be aware of this
      potential toxicity of therapy.

PMID- 15140553
TI  - SYT-SSX fusion genes in synovial sarcoma of the thorax.
AB  - Synovial sarcoma (SS) is characterized by a chromosomal translocation resulting
      in the expression of an SYT-SSX chimeric transcript, usually SYT-SSX1 or SYT
      SSX2. Synovial sarcoma typically originates in the limbs, and its location in the
      thorax is rare. Synovial sarcomas are usually classified into three histologic
      subtypes: biphasic, monophasic and poorly differentiated tumors. The detection of
      the characteristic chimeric transcript often contributes to a histopathological
      diagnosis, especially when the tumor arises in an unusual location. Previous
      studies have shown that SYT-SSX1 is the most common SYT-SSX fusion transcript in
      biphasic synovial sarcomas of the limbs. Here, we report two cases of synovial
      sarcoma originating in the thorax. The presence of SYT-SSX2 chimeric transcripts
      was confirmed by reverse transcript polymerase chain reaction (RT-PCR) and a
      direct sequencing analysis in both cases. The tumor in case 1 originated from the
      pericardium, which is an exceedingly rare site for primary synovial sarcoma; only
      three other cases of synovial sarcoma originating in the pericardium have been
      previously reported. Case 2 exhibited a biphasic synovial sarcoma of the
      mediastinum containing an SYT-SSX2 fusion transcript, which is a rare fusion type
      in biphasic synovial sarcomas of the limbs. We reviewed previous reports of
      thoracic synovial sarcomas containing an analysis of the SYT-SSX fusion
      transcript and found that case 2 in the present study was the first description
      of a biphasic synovial sarcoma of the thorax with an SYT-SSX2 fusion transcript.
      However, the number of reported cases was not sufficient to conclude that SYT
      SSX2 fusion in biphasic synovial sarcoma of the thorax is, indeed, rare. Further
      genetic analysis is needed to fully understand the biological and clinical
      features of synovial sarcoma originating in the thorax.

PMID- 15140554
TI  - Population-based outcomes for SCLC.

PMID- 15140556
TI  - Genetic alteration on 8q distinct from MYC in bronchial carcinoma in situ
      lesions.

PMID- 15140557
TI  - Ionotropic glutamate receptor GluR2/3-immunoreactive neurons in the cat, rabbit,
      and hamster superficial superior colliculus.
AB  - Ionotropic glutamate receptor (GluR) subtypes occur in various types of cells in
      the central nervous system. We studied the distribution of AMPA glutamate
      receptor subtype GluR2/3 in the superficial layers of cat, rabbit, and hamster
      superior colliculus (SC) with antibody immunocytochemistry and the effect of
      enucleation on this distribution. Furthermore, we compared this labeling to that
      of calbindin D28K and parvalbumin. Anti-GluR2/3-immunoreactive (IR) cells formed
      a dense band of labeled cells within the lower superficial gray layer (SGL) and
      upper optic layer (OL) in the cat SC. By contrast, GluR2/3-IR cells formed a
      dense band within the upper OL in the rabbit and within the OL in the hamster SC.
      Calbindin D28K-IR cells are located in three layers in the SC: one within the
      zonal layer (ZL) and the upper SGL in all three animals, a second within the
      lower OL and upper IGL in the cat, within the IGL in the rabbit and within the OL
      in the hamster, and a third within the deep gray layer (DGL) in all three
      animals. Many parvalbumin-IR neurons were found within the lower SGL and upper
      OL. Thus, the GluR2/3-IR band was sandwiched between the first and second layers
      of calbindin D28K-IR cells in the cat and rabbit SC while the distribution of
      GluR2/3-IR cells in the hamster matches the second layer of calbindin D28K-IR
      cells. The patterned distribution of GluR2/3-IR cells overlapped the tier of
      parvalbumin-IR neurons in cat, but only partially overlapped in hamster and
      rabbit. Two-color immunofluorescence revealed that more than half (55.1%) of the
      GluR2/3-IR cells in the hamster SC expressed calbindin D28K. By contrast, only
      9.9% of GluR2/3-IR cells expressed calbindin D28K in the cat. Double-labeled
      cells were not found in the rabbit SC. Some (4.8%) GluR2/3-IR cells in the cat SC
      also expressed parvalbumin, while no GluR2/3-IR cells in rabbit and hamster SC
      expressed parvalbumin. In this dense band of GluR2/3, the majority of labeled
      cells were small to medium-sized round/oval or stellate cells. Immunoreactivity
      for the GluR2/3 was clearly reduced in the contralateral SC following unilateral
      enucleation in the hamster. By contrast, enucleation appeared to have had no
      effect on the GluR2/3 immunoreactivity in the cat and rabbit SC. The results
      indicate that neurons in the mammalian SC express GluR2/3 in specific layers,
      which does not correlate with the expression of calbindin D28K and parvalbumin
      among the animals.

PMID- 15140558
TI  - Brain potentials index executive functions during random number generation.
AB  - The generation of random sequences is considered to tax different executive
      functions. To explore the involvement of these functions further, brain
      potentials were recorded in 16 healthy young adults while either engaging in
      random number generation (RNG) by pressing the number keys on a computer keyboard
      in a random sequence or in ordered number generation (ONG) necessitating key
      presses in the canonical order. Key presses were paced by an external auditory
      stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms)
      sequences in separate runs. Attentional demands of random and ordered tasks were
      assessed by the introduction of a secondary task (key-press to a target tone).
      The P3 amplitude to the target tone of this secondary task was reduced during
      RNG, reflecting the greater consumption of attentional resources during RNG.
      Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of
      the pacing stimulus, whenever the subjects produced a true random response. This
      negativity could be attributed to the left dorsolateral prefrontal cortex and was
      absent when numbers were repeated. This negativity was interpreted as an index
      for the inhibition of habitual responses. Finally, in response locked ERPs a
      negative component was apparent peaking about 50 ms after the key-press that was
      more prominent during RNG. Source localization suggested a medial frontal source.
      This effect was tentatively interpreted as a reflection of the greater monitoring
      demands during random sequence generation.

PMID- 15140559
TI  - Overall distribution of GLYT2 mRNA-containing versus GAD67 mRNA-containing
      neurons and colocalization of both mRNAs in midbrain, pons, and cerebellum in
      rats.
AB  - We aimed to clarify the overall distribution of glycinergic neurons in the
      midbrain, pons, and cerebellum in rats, using in situ hybridization for mRNA
      encoding glycine transporter 2 (GLYT2), which reliably detects glycinergic cell
      bodies. We combined this method with in situ hybridization for mRNA encoding
      glutamic acid decarboxylase isoform 67 (GAD67), and have presented for the first
      time global and detailed views of the distribution of glycinergic neurons in
      relation to GABAergic neurons. In addition to this single-detection study, we
      performed double-detection of GLYT2 mRNA and GAD67 mRNA to determine the
      distribution of neurons co-expressing these mRNAs. We have shown that many areas
      of the brainstem and cerebellum, not only areas where previous
      immunohistochemical studies have specified, involve double-labeled neurons with
      GLYT2 and GAD67 mRNAs. In particular, when lightly labeled GLYT2 mRNA-positive
      neurons were distributed within the area of GAD67 mRNA-positive neurons, almost
      all such GLYT2 mRNA-positive neurons were GAD67 mRNA-positive. Areas or neuron
      groups expressing exclusively GLYT2 mRNA or GAD67 mRNA were rather limited, such
      as the superior colliculus, nucleus of the trapezoid body, and Purkinje cells.
      The present study suggests that the corelease of glycine and GABA from single
      neurons is more widespread than has been reported.

PMID- 15140560
TI  - Change in phase synchronization of local field potentials in anesthetized rats
      after chronic dopamine depletion.
AB  - In order to investigate temporal characteristics of oscillatory neural activity
      and the effect of chronic dopamine depletion on it, local field potentials were
      measured in anesthetized rats without or with a 6-OHDA lesion at either the
      ventral tegmental area or the substantia nigra compacta, using a pair of
      electrodes that were separated by 120 microm. Coupling of neural activity in this
      mesoscopic scale was measured by a synchronization index that quantified the
      distribution of differences in instantaneous phase between the two potentials
      recorded. Phase synchrony was significantly stronger at deep basal ganglia sites,
      more so than at cortical sites, over a gamma range (30-120 Hz) in normal rats.
      After chronic dopamine depletion, this synchrony was no longer observable,
      especially after a substantia nigra lesion, while there was an increase in phase
      synchrony in the cortex at a lower frequency band (10 Hz). These findings are
      consistent with previously reported findings that the effect of dopaminergic
      innervation on oscillatory neural activity varies from synchronizing to
      desynchronizing, depending on the structure innervated and the frequency of the
      oscillation.

PMID- 15140561
TI  - Expression of estrogen receptors (alpha, beta) and androgen receptor in serotonin
      neurons of the rat and mouse dorsal raphe nuclei; sex and species differences.
AB  - Sex steroids have been inferred to be involved in the regulation of affective
      status at least partly through the serotonergic (5-HT) system, particularly in
      the dorsal raphe nucleus (DRN), which innervates enormous projections to the
      cerebral cortex and limbic system. In the present study, the expression of
      estrogen receptors-alpha and -beta (ERalpha, ERbeta), androgen receptor (AR) and
      5-HT was examined immunohistochemically in the rat and mouse DRN in both sexes.
      The results showed that large numbers of ERalpha- and/or ERbeta-immunoreactive
      (ERalpha-I, ERbeta-I) cells were found in the DRN of both male and female mice,
      whereas only small numbers of ERalpha-I cells and no ERbeta-I cells were seen in
      the rat DRN of each sex. With respect to AR-immunoreactive (AR-I) cells, moderate
      numbers of such cells were present only in male rats and mice, and no or very few
      could be observed in female ones. The ERalpha-I, ERbeta-I, and AR-I cells were
      mainly distributed in the rostral DRN. In double-immunostaining, many 5-HT-I
      neurons were found to show ERalpha and/or ERbeta expression specifically in the
      rostral DRN (particularly dorsal, ventral and interfascicular parts) of mice of
      both sexes, but not in that of rats. In contrast, only a few 5-HT neurons were
      observed to show AR expression in the DRN of both rodents. The current results
      strongly suggest that sex steroids can modulate the affective regulation of the
      serotonergic system through ERalpha and/or ERbeta in 5-HT neurons of the mouse
      rostral DRN (but not so much through AR), and that such effects might be
      different depending on the sex and species, as shown by the prominent sex
      differences in AR expression and prominent species differences in ERalpha and
      ERbeta expression.

PMID- 15140562
TI  - Toosendanin, a triterpenoid derivative, increases Ca2+ current in NG108-15 cells
      via L-type channels.
AB  - Toosendanin, a triterpenoid derivative extracted from Melia toosendan Sieb et
      Zucc, was demonstrated to be a selective presynaptic blocker and an effective
      antibotulismic agent in previous studies. Here, we observed its effects on Ca(2+)
      channels in NG108-15 cells by whole-cell patch-clamp recording. Obtained data
      showed that toosendanin concentration dependently increased the high-voltage
      activated (HVA) Ca(2+) current with an EC(50) of 5.13 microM in differentiated
      NG108-15 cells. The enhancement effect was still observed when the cells were
      pretreated with 5 microM omega-conotoxin MVIIC. However, when the cells were
      preincubated with 5 microM nifedipine or 10 microM verapamil-containing solution,
      the effect was absent. In undifferentiated NG108-15 cells, which only express T
      type Ca(2+) channels, toosendanin did not affect Ca(2+) currents. These results
      show that toosendanin increases Ca(2+) influx in NG108-15 cells via L-type Ca(2+)
      channels.

PMID- 15140563
TI  - Antisense knockdown of drebrin A, a dendritic spine protein, causes stronger
      preference, impaired pre-pulse inhibition, and an increased sensitivity to
      psychostimulant.
AB  - Drebrin located in dendritic spines regulates their morphological changes and
      plays a role in the synaptic plasticity via spine function. Reduced drebrin has
      been found in the brain of patients with Alzheimer's disease or Down's syndrome.
      To examine whether the down-regulation of drebrin protein levels causes deficits
      in higher brain function, such as memory or cognition, we performed antisense
      induced knockdown of drebrin A expression in rat brain using an hemagglutinating
      virus of Japan (HVJ)-liposome gene transfer technique. We investigated the
      effects of drebrin in vivo knockdown on spatial memory in a water-maze task,
      sensorimotor gating in a pre-pulse-inhibition test, adaptive behaviors in an open
      field test, and sensitivity to psychostimulant in an amphetamine-induced
      locomotor response. Rats with drebrin A in vivo knockdown displayed a stronger
      preference for a previous event due to perseverative behavior, impaired pre-pulse
      inhibition (PPI), increased locomotor activity, anxiety-like behavior, and an
      increased sensitivity to psychostimulant, suggesting behaviors related to
      schizophrenia. These findings indicated that decreased drebrin produces deficits
      in cognitive function but not in spatial memory, probably via hypofunction of
      dendritic spines.

PMID- 15140564
TI  - GABAA-receptor-mediated increase in intracellular Ca2+ concentration in the
      regenerating retina of adult newt.
AB  - We used optical recording with the Ca(2+)-sensitive dye, fura-2, in living slice
      preparations from the newt retina at different stages of regeneration. gamma
      Aminobutyric acid (GABA) induced pronounced [Ca(2+)](i) rise in progenitor cells
      and differentiating ganglion cells in the 'intermediate' stage of retinal
      regeneration. This [Ca(2+)](i) rise became less pronounced at the beginning of
      synapse formation in the late regenerating retina. At the late period of the late
      regenerating retina with the IPL thickness comparable to that of the control
      retina, GABA-induced [Ca(2+)](i) rise became undetectable or sometimes a small
      decrease in [Ca(2+)](i) was observed in regenerated ganglion cells. In contrast,
      N-methyl-d-aspartate (NMDA)-induced [Ca(2+)](i) rise appeared in premature
      ganglion cells and became prominent gradually as the regeneration proceeded. The
      [Ca(2+)](i) rise to GABA was mediated by GABA(A) receptors. This was shown by
      inhibition of GABA-induced Ca(2+) response with the preincubation of the GABA(A)
      receptor antagonist, bicuculline. The [Ca(2+)](i) rise due to GABA was suppressed
      in the absence of extracellular Ca(2+) or in the presence of the L-type voltage
      gated Ca(2+) channel blocker, verapamil, suggesting that Ca(2+) may be entered
      through L-type Ca(2+) channels. Transient appearance of [Ca(2+)](i) rise to GABA
      during regeneration and origin of GABA-induced [Ca(2+)](i) rise were similar to
      those in the developing retina [J. Neurobiol. 24 (1993) 1600]. These similarities
      may suggest that common mechanisms may control neurogenesis and/or synaptogenesis
      during development and regeneration.

PMID- 15140565
TI  - Stress-facilitated LTD induces output plasticity through synchronized-spikes and
      spontaneous unitary discharges in the CA1 region of the hippocampus.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) of the excitatory
      synaptic inputs plasticity in the hippocampus is believed to underlie certain
      types of learning and memory. Especially, stressful experiences, well known to
      produce long-lasting strong memories of the event themselves, enable LTD by low
      frequency stimulation (LFS, 3 Hz) but block LTP induction by high frequency
      stimulation (HFS, 200 Hz). However, it is unknown whether stress-affected
      synaptic plasticity has an impact on the output plasticity. Thus, we have
      simultaneously studied the effects of stress on synaptic plasticity and neuronal
      output in the hippocampal CA1 region of anesthetized Wistar rats. Our results
      revealed that stress increased basal power spectrum of the evoked synchronized
      spikes and enabled LTD induction by LFS. The induction of stress-facilitated LTD
      but not LFS induced persistent decreases of the power spectrum of the
      synchronized-spikes and the frequency of the spontaneous unitary discharges;
      However, HFS induced LTP in non-stressed animals and increased the power spectrum
      of the synchronized-spikes, without affecting the frequency of the spontaneous
      unitary discharges, but HFS failed to induce LTP in stressed animals without
      affecting the power spectrum of the synchronized-spikes and the frequency of the
      spontaneous unitary discharges. These observations that stress-facilitated LTD
      induces the output plasticity through the synchronized-spikes and spontaneous
      unitary discharges suggest that these types of stress-related plasticity may play
      significant roles in distribution, amplification and integration of encoded
      information to other brain structures under stressful conditions.

PMID- 15140566
TI  - A quantitative analysis of the laminar distribution of synaptic boutons in field
      CA3 of the rat hippocampus.
AB  - We analyzed the laminar distribution of synaptic boutons in field CA3 of the rat
      hippocampus using a large montage electron micrograph. The size of boutons and
      synaptic vesicles was measured using a computer-assisted digitizing system. In
      all, 3353 synaptic boutons were observed in a 15 microm x 100 microm strip. Of
      these, 86.3% contained spherical vesicles (S-boutons), 12% contained flat
      vesicles (F-boutons), and 1.7% were mossy terminals (M-boutons). S-boutons were
      distributed widely in the strata moleculare (st. Mol), radiatum (st. Rad), and
      oriens (st. Ori), but there were only a few in the strata lucidum (st. Luc) and
      pyramidale (st. Pyr). The upper portions of both the st. Rad and Ori contained
      slightly fewer boutons. In terms of the location of synaptic contacts, 83% of all
      S-boutons were found on the dendritic spines and the rest were on the dendritic
      shafts. S-boutons on the dendritic shafts were observed more frequently in the
      st. Mol than in the other strata. According to the morphometry of the size of
      synaptic vesicles, S-boutons with small vesicles (mean vesicle area <1109 nm(2))
      were located exclusively in the st. Mol, S-boutons with medium-sized vesicles
      (mean vesicle area 1109-1482 nm(2)) were observed in all strata, and S-boutons
      with large vesicles (mean vesicle area >1482 nm(2)) were distributed in the st.
      Luc and Ori, but not in the st. Mol. F-boutons were predominantly distributed in
      the upper half of the st. Mol and in the area around the st. Pyr, although they
      were observed in all strata. In the st. Mol, all the F-boutons were in contact
      with dendritic shafts, while near the st. Pyr, F-boutons were found exclusively
      on somata, the proximal parts of the dendritic shafts, and the initial segments
      of axons. The average F-bouton was smaller in the st. Mol (0.23 microm(2)) than
      near the st. Pyr (0.39 microm(2)). In this synapto-architectural study of the
      hippocampal CA3 region using large montage electron micrographs, we observed (1)
      an intimate relationship between synapse distribution and the dendritic structure
      of pyramidal neurons, (2) the distribution of different types of boutons
      containing vesicles of various size, and (3) two different plausible foci of
      postsynaptic inhibition where F-boutons were distributed densely, and (4)
      estimated the input ratios of pyramidal neurons.

PMID- 15140567
TI  - Quantitative magnetic detection of finger movements in patients with Parkinson's
      disease.
AB  - To develop a new measurement tool for quantitatively detecting the finger
      movement of a patient with Parkinson's disease (PD), we designed a magnetic
      sensing system consisting of a magnetic induction coil, a sensing coil, and a
      circuit unit. The sensing coil detects the inducted magnetic field that varies
      with the distance between the two coils, and the detected signals are demodulated
      in the circuit unit in order to obtain the variation voltage from the oscillation
      frequency. To obtain a coefficient for converting voltage to distance, we
      measured the output voltages for seven fixed finger positions of 12 normal
      volunteers. The voltage differences corresponding to the finger movement in 20 PD
      patients, six age-matched controls, and 12 normal volunteers were then recorded
      for 30s. To investigate the velocity and acceleration of the finger movement, we
      calculated their waveforms from the measured displacement waveform. We also
      detected the main frequency of the tapping rhythm by using a fast Fourier
      transform (FFT). The averaged amplitude of each waveform decreased with the
      disorder in the Hoehn-Yahr (HY) stage, while the averaged tapping frequency of PD
      patients did not have any correlation with this stage. It can be concluded that
      this magnetic sensing system can assess finger movement quantitatively.

PMID- 15140568
TI  - Functionally deficient neuronal differentiation of mouse embryonic neural stem
      cells in vitro.
AB  - Embryonic mouse neural stem cells (NSCs) were isolated from E14 mice, multiplied
      in medium containing epidermal growth factor (EGF) and basic fibroblast growth
      factor (bFGF) and plated in laminin-coated wells in basic serum-free neurobasal
      medium. After 7 days in vitro, approximately 20% of the embryonic mouse NSCs
      developed into morphologically and biochemically fully maturated neurons, with
      extensive dendrites and multiple synaptic contacts. However, even after 22 days
      of culture, none of these neurons developed voltage-dependent sodium-channels
      characteristic for a functional neuron. Apparently, the morphological
      differentiation and the electrophysiological maturation of an embryonic mouse NSC
      into a neuron are independently regulated.

PMID- 15140569
TI  - Event-related potentials and EMDR treatment of post-traumatic stress disorder.
AB  - Ten patients suffering from post-traumatic stress disorder (PTSD) following a
      severe traumatic event, were assessed with event-related brain potentials (ERPs)
      in a modified oddball paradigm containing auditory standard, target, and novel
      tones. ERPs were assessed before and after a treatment session using the eye
      movement desensitization and reprocessing method. Compared to a control group
      that underwent sham treatment, ERPs of the patients showed a reduction of the P3a
      component in the post-treatment recording, suggesting a reduced orienting to
      novel stimuli and reduced arousal level after the treatment. Moreover,
      psychometric assessment revealed a marked improvement of the PTSD symptoms after
      treatment.

PMID- 15140570
TI  - Involvement of CTLA-4 in T-cell anergy induced by staphylococcal enterotoxin A in
      vitro.
AB  - Superantigens, like staphylococcal enterotoxin A (SEA), induce a strong
      proliferative response followed by clonal deletion of a substantial portion of
      defined V(beta) T-cells. The remaining cells display in vitro anergy. Anergy is a
      major mechanism to ensure antigen-specific tolerance in T-lymphocyte in the
      adult. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter
      receptors CD28/CTLA-4 play pivotal roles in T-cell activation and immune
      regulation. While increasing data further suggested a role for CTLA-4 in
      regulating T-cell tolerance in vivo, the mechanism by which CTLA-4 influences T
      lymphocyte tolerance is unclear. In the present study, we established an in vitro
      anergy model using superantigen SEA as the anergizing agents and examined CD3,
      CD28 and CTLA-4 expression of anergic T-cells in response to SEA rechallenge. It
      is found that anergic T-cell fails to produce the autocrine growth factor
      interleukin-2 (IL-2) upon stimulation, and addition of exogenous IL-2 can reverse
      the anergic state. Both TCR/CD3 complex and CD28 expression is not reduced in
      anergic cells during whole immune response, but the expression of CTLA-4 on the
      cell surface is enhanced dramatically in the late stages of an immune response.
      Using CTLA-4/B7-blocking agent, we found T-cell anergy was aborted and anergic T
      cells restored the ability to proliferate and produce IL-2, suggesting that CTLA
      4 may play a critical role in the induction of T-cell anergy.

PMID- 15140571
TI  - Enhanced apoptotic activity of a structurally optimized form of galectin-1.
AB  - Galectin-1 is a homodimeric protein with potent anti-inflammatory properties due
      to its ability to induce apoptosis in thymocytes and T cells. The galectin-1
      subunits are not covalently linked but the monomers are in a dynamic equilibrium
      with the dimeric form. Since the affinity of the monomers for each other is
      rather low (in the range of 10(-5)M), the in vivo efficacy of galectin-1 is
      limited because the equilibrium is shifted towards the inactive monomeric form at
      lower concentrations. In order to overcome this problem, we designed a covalently
      linked form of the dimer based on the galectin-1 crystal structure. Here we show
      that this irreversibly dimeric form of galectin-1 is a potent inducer of
      apoptosis in murine thymocytes as well as murine mature T cells at concentrations
      10-fold lower than wild-type galectin-1. This structurally optimized form of
      galectin-1 may therefore be a potentially powerful tool to treat chronic
      inflammatory diseases.

PMID- 15140572
TI  - Functional analysis of Cobra Venom Factor/human C3 chimeras transiently expressed
      in mammalian cells.
AB  - The complement activating venom component Cobra Venom Factor (CVF), a functional
      and structural homologue of the human complement component C3, forms a stable CVF
      dependent C3 convertase complex, which, in contrast to C3-dependent convertase
      effects continuous activation of the complement and, thereby, decomplementation.
      In order to elucidate the mechanism underlying the enhanced activity of CVF
      compared to human C3, we generated two CVF/C3 chimeras and established different
      affinity-based assay systems for functional analysis of these constructs. To
      allow for convenient expression and subsequent functional characterisation, the
      CVF/C3 chimeras as well as CVF and C3 were transiently expressed in mammalian
      cells. Problems due to the low concentration of the recombinant proteins in the
      supernatants of transient expressions were circumvented by fusion to peptide tags
      enabling their efficient immobilisation onto suitable surfaces and subsequent
      characterisation. In an alternative approach monoclonal antibody fragments
      generated from a semisynthetic phage display scFv library were employed for
      concentrating the recombinant proteins by immunoprecipitation. Utilising both
      approaches all transiently expressed proteins could be characterised for their
      complement consumption activity. The data obtained with the CVF/C3 chimeras
      demonstrate that the increased stability of the CVFBb complex is independent of
      the domains in CVF corresponding to binding sites of factor B and H and the
      cleavage sites of factor I in the human C3 molecule.

PMID- 15140573
TI  - Immunological aspects of heat-shock proteins-the optimum stress of life.
AB  - This review summarizes the complex role of heat-shock proteins (Hsp) in immune
      reactions, especially the cellular effects of heat-shock proteins during the
      recognition processes by innate immunity. The role of heat-shock proteins in the
      pathogenesis of two multifactorial diseases, i.e. inflammatory bowel disease
      (IBD) and atherosclerosis is highlighted. A new hypothesis on "immunodeficiency
      burden" is presented. According to this hypothesis, susceptibility to any
      multifactorial disease in any given subject and in the presence of specific
      environmental factors is the aggregate effect of polymorphisms resulting in the
      failure of protective immunity with consequent disease.

PMID- 15140574
TI  - Implication of PKA and PKC in the activation of the haemocytes of Mytilus
      galloprovincialis Lmk by LPS and IL-2.
AB  - LPS and IL-2 play an essential role in the generation of the immune response in
      diverse eukaryotic species, as they provoke the activation of several pathways of
      signal transduction in macrophages. Among the kinases related to these pathways,
      PKA and the PKCs are some of the most important. In the haemolymph of the marine
      mussel Mytilus galloprovincialis Lmk, the cells responsible for the defence
      reactions are the haemocytes. These act as active phagocytes, and are able also
      to secrete humoral factors. The effect of the stimulation of the haemocytes with
      either LPS or IL-2 on the expression of both a Ca(2+)-independent PKC (p105) and
      a regulatory subunit (RII) of PKA found in mussel tissues are studied in this
      work. Also, the effect of inhibitors specific for these kinases on their
      expression and on their release of catecholamines is reported.

PMID- 15140575
TI  - Human NKG2F is expressed and can associate with DAP12.
AB  - The NKG2 family of C-lectin type molecules is important for regulating the
      function of natural killer and subpopulations of T cells. NKG2A/B contains an
      immunoreceptor tyrosine-based inhibitory motif (ITIM) and accordingly functions
      as an inhibitory receptor, whereas NKG2C and -E/H associate with DAP12 via a
      positively charged residue in their transmembrane domains and function as
      activation receptors. Each of these molecules is paired with CD94 for expression
      and recognizes HLA-E as a ligand. NKG2F is an orphan gene within the NKG2 family
      whose translated product would contain both a positively charged residue in its
      transmembrane region, an intracellular ITIM-like sequence and an extracellular
      domain (62 residues) that is truncated relative to other NKG2 molecules. We show
      that NKG2F is expressed as a protein in NK cells. Expression appears to be
      confined to intracellular compartments probably due to its inability to associate
      with CD94. It can however associate with DAP12 thereby providing activation
      signaling potential. We were unable to demonstrate phosphorylation of the Tyr
      residue in the ITIM-like motif suggesting that it is a mock ITIM. NKG2F could be
      a receptor component with an as yet unidentified partner(s), could function to
      regulate cell activation through competition for DAP12 with other receptors, such
      as NKG2C and -E/H, or it could simply be a vestigial gene product.

PMID- 15140577
TI  - Addition of an extra immunoglobulin domain to two anti-rodent TNF monoclonal
      antibodies substantially increased their potency.
AB  - The functional valency of a monoclonal antibody (mAb) has important influences on
      such things as antigen avidity, Fc-mediated immune effector functions, and
      clearance of immune complexes. cV1q, a neutralizing rat/mouse chimeric anti-mouse
      tumor necrosis factor (TNF) monoclonal antibody (mAb), and Rt108, a neutralizing
      mouse anti-rat TNF (anti-raTNF) mAb, appear to be functionally monovalent for TNF
      binding despite containing two antigen binding sites. The functional monovalency
      of these two independent anti-rodent TNF mAbs is presumably a result of steric
      hindrance from one TNF molecule binding to one Fab arm that prevents binding of a
      second TNF molecule to the other Fab arm. To test whether this steric hindrance
      could be overcome by introducing extra space and flexibility between the Fab
      arms, these mAbs were engineered to contain an extra CH1 immunoglobulin domain
      between the CH1 and hinge domains of their heavy chains. In vitro binding data
      showed that, compared to the original mAbs, the modified mAbs (S-mAbs) had
      greater capability of binding two TNF molecules simultaneously. In vitro activity
      assays showed that, compared to the original mAbs, the S-mAbs had significantly
      greater TNF-neutralization potency, with the S-mAb version of cV1q (S-cV1q) being
      200-fold more effective at blocking mouse TNF (muTNF) and the S-mAb version of
      Rt108 (S-Rt108) being 20-fold more effective at blocking raTNF. Similar results
      were observed in vivo, where S-cV1q was between 100- and 500-fold more protective
      than cV1q in mice challenged with endotoxin. These data reveal that introduction
      of another constant region immunoglobulin domain into two unrelated mAbs
      dramatically enhanced their neutralization potency. Other mAbs may also show more
      potent activity using this engineering approach, particularly mAbs that recognize
      homopolymeric antigens.

PMID- 15140576
TI  - Complex mechanisms for inhibition of immunoglobulin gene expression in a germinal
      center B cell line.
AB  - CD40 ligation and IL-4 stimulation are critical Th2 cell-derived signals that act
      on germinal center B cells to stimulate immunoglobulin isotype switching. In
      addition to this well-known effect, these same Th2 signals have also been
      reported to inhibit ongoing immunoglobulin synthesis in germinal center B cells.
      To study the mechanism of this inhibition, we have investigated which
      immunoglobulin gene regulatory regions might be affected by IL-4 and CD40 Ligand
      (CD40L). CL-01 cells, a human B cell line of germinal center phenotype, were
      transiently transfected with luciferase reporter constructs containing various
      light and heavy chain enhancers and promoters; the cells were then incubated with
      or without CD40L and IL-4 and then assayed for luciferase expression. We find
      that the intronic enhancer of the kappa light chain (but not the heavy chain) is
      upregulated by CD40 ligation, but that VH and Vkappa promoters and the 3'
      enhancers of both the kappa and heavy chain loci are inhibited by CD40 ligation
      and the Th2 cytokines IL-4 and IL-10. The inhibitory response of the 3'alpha
      enhancer can be observed with a 130 bp core fragment of the enhancer, and remains
      unaffected by mutations in several motifs known or suspected to contribute to
      enhancer function. The ultimate effects of cytokines and CD40 ligation on
      immunoglobulin gene transcription therefore represent a complex integration of
      positive and negative stimuli acting on enhancers and promoters.

PMID- 15140578
TI  - Functional analysis in serum from atypical Hemolytic Uremic Syndrome patients
      reveals impaired protection of host cells associated with mutations in factor H.
AB  - A subgroup of patients with the most severe form of the Hemolytic Uremic Syndrome
      (HUS) presents mutations in the complement regulatory protein factor H. The
      functional analyses of the factor H mutant proteins purified from some of these
      patients have shown a specific defect in the capacity to control complement
      activation on cellular surfaces. Here, we show that these factor H-related
      complement regulatory defects can be detected in the patients' serum with a
      simple hemolytic assay. Data obtained from HUS patients and control individuals
      indicate that this assay is a useful tool for the molecular diagnosis of factor H
      related HUS.

PMID- 15140579
TI  - Characterization of Tollip protein upon Lipopolysaccharide challenge.
AB  - Tollip protein serves as a suppressor of innate immunity signaling with unknown
      mechanism. In this report, we observed that Tollip preferentially bound with
      phosphatidylinositol-3-phosphate (PtdIns(3)P) and phosphatidylinositol-3,4,5
      phosphate (PtdIns(3,4,5)P) in vitro. Mutation of lysine 150 to glutamic acid
      (Tollip(KE)) within the C2 domain abolished such binding, indicating that C2
      domain is critically involved. We demonstrated that overexpression of Tollip
      inhibited NFkB reporter gene transcription. On the contrary, overexpression of
      Tollip(KE) mutant has no inhibitory effect on LPS-induced NFkB reporter activity.
      Tollip binding with 3'-phosphorylated phosphatidylinositides implies that PI3
      kinase may regulate its function. We observed that Tollip-mediated inhibition
      could be alleviated by wortmannin. We also showed that pretreatment with
      wortmannin augmented LPS-induced endogenous IL-1beta gene expression in monocytic
      THP-1 cells. THP-1 cells with prolonged LPS treatment develop a state of
      hyporesponsiveness and no longer respond to further LPS challenge in terms of IL
      1beta gene expression. Here we demonstrated that Tollip protein levels were
      increased following LPS treatment in THP-1 cells as well as in human primary
      blood mononuclear cells. Increased protein stability upon LPS challenge was
      likely the cause for the Tollip protein increase. Upon over expression with an
      enhanced green fluorescent tag, Tollip localized to Golgi apparatus. Our study
      provides yet another mechanism for suppressing excessive TLR signaling activation
      mediated by Tollip.

PMID- 15140580
TI  - The difference of binding epitopes on human CD16 (FcgammaRIII) interacted with
      hIgG1 and monoclonal antibody B88-9.
AB  - The 3-D complex structures of extracellular domain of human CD16 (FcgammaRIII)
      and hIgG1 or B88-9 were obtained by means of computer-guided molecular modeling,
      respectively. The binding epitopes were predicted and binding energy was
      calculated theoretically. The epitopes of human CD16 interacted with hIgG1 and
      B88-9 were different and the binding energy of B88-9 was stronger than hIgG1. The
      computer competing simulation results showed that B88-9 could bind to CD16 when
      CD16 was also bound by hIgG1, while IgG1 could not bind to CD16 after CD16 was
      bound by B88-9. By flow cytometry analysis, the competitive binding activity of
      B88-9 to CD16 with hIgG1 was evaluated. With the increasing concentrations of
      hIgG1, the binding activity of B88-9 was not interfered markedly. It suggested
      that hIgG1 could not inhibit the interaction of CD16 and B88-9 and the binding
      domain of hIgG1 and B88-9 on CD16 was different.

PMID- 15140581
TI  - Genetic association analysis of myocardial infarction with thrombospondin-1 N700S
      variant in a Chinese population.
AB  - INTRODUCTION: Thrombospondin-1 (TSP-1) is very important in platelet adhesion and
      aggregation, inflammation, cell to cell interaction, and vascular smooth muscle
      cell proliferation. Therefore, it may play an important role in the progression
      of cardiovascular disease. Recently, the TSP-1 N700S variant was proposed to be a
      new genetic predictor for myocardial infarction (MI) in American population, but
      the hypothesis was not verified in two other populations. We investigated a
      possible association between the N700S polymorphism and MI in a Chinese Han
      population. MATERIALS AND METHODS: We performed a case-control study including
      406 patients who survived an acute MI before age 60 years and 400 age- and sex
      matched controls. The N700S polymorphism was determined by polymerase chain
      reaction and restriction fragment length polymorphism. RESULTS: Of the 806
      subjects participating in the study, only 7 of the heterozygotes and none of the
      homozygotes were detected for the 700S allele. The prevalence of the S allele in
      the healthy controls was less frequent than those of the west populations (0.3%
      vs. 11%). No association of the N700S polymorphism with an altered risk of MI was
      found in our study (GA vs. AA: OR=2.48; 95% CI, 0.48 to 12.86; P=0.46).
      CONCLUSIONS: Our study suggested that the TSP-1 N700S polymorphism was rare and
      unrelated to MI in the Chinese Han population. Additional investigations should
      be performed in populations at different risk for coronary events in order to
      further elucidate the possible contribution of the polymorphism to cardiovascular
      disease.

PMID- 15140582
TI  - Characterization of the postglomerular renal metabolism of lepirudin in healthy
      volunteers.
AB  - INTRODUCTION: The anticoagulant r-hirudin lepirudin is eliminated exclusively via
      the kidneys. We examined the C-terminal amino acid degradation of lepirudin by
      the proximal kidney tubulus cells in humans as well as the antithrombotic
      efficacy of the metabolites and quantified the metabolite portions. MATERIALS AND
      METHODS: In vitro metabolites of lepirudin were produced by adding 250 microg
      lepirudin to urine of three healthy volunteers and a concentration of 100 ml
      fresh urine to 1.5 ml and subsequent separation by high performance liquid
      chromatography. Anticoagulant activities of the mass spectrometrically identified
      metabolites were measured by ecarin clotting time and protein determination with
      bicinchoninic acid. In 10 healthy volunteers 1 mg lepirudin was administered
      intravenously, urine was collected during the following 2 h. The urine amount
      containing 50 microg lepirudin measured by ecarin clotting time was enzyme
      inactivated and measured analogously to the in vitro samples. RESULTS: The in
      vitro generated metabolites were shortened amino acid by amino acid at the C
      terminal end, up to five amino acids. Their anticoagulant activity was reduced to
      92.6% (M64), 80.1% (M63) and 74.4% (M60,61,62) in comparison to lepirudin.
      Lepirudin (57.9 +/- 8.6%) was eliminated unchanged via the kidneys. Identical to
      the in vitro situation metabolite fragments were built in the distribution M64 =
      8.1 +/- 5.7%, M63 = 21.1 +/- 6.5%, and M60,61,62 = 12.9 +/- 4.5%. CONCLUSIONS:
      Lepirudin is metabolized spontaneously in more than 10-fold concentrated urine.
      Metabolization of lepirudin takes place in the proximal tubulus cells as well. In
      vitro, the degradation takes place amino acid by amino acid, but in vivo even
      dipeptides and perhaps tripeptides are degraded.

PMID- 15140583
TI  - Lack of uniform platelet activation in patients after ischemic stroke and choice
      of antiplatelet therapy.
AB  - INTRODUCTION: Platelets play an important role in the natural history of ischemic
      stroke, and are known to be activated in the acute phase. Although aspirin
      reduces risks of myocardial infarction, stroke and cardiovascular death, the
      extent of platelet action and the effect of aspirin on platelet function in
      patients recovering from stroke remain unclear. METHODS: We studied 120
      individuals divided into three equal groups: aspirin-free patients after ischemic
      stroke, post-stroke patients receiving aspirin (81-650 mg/daily), and aspirin
      free subjects with multiple risk factors for vascular disease. Conventional
      platelet aggregation induced by 5 microM ADP and 5 microM epinephrine, cartridge
      based analyzers (Ultegra, and PFA-100) readings, and expression of CD31, CD41a,
      CD42b, GPIIb/IIIa activity, CD51/CD61, CD62p, CD63, CD107a, CD154, CD165,
      formation of platelet-monocyte aggregates, intact (SPAN12), and cleaved (WEDE15)
      PAR-1 thrombin receptors by flow cytometry were analyzed. RESULTS: There were no
      differences between aspirin-free post-stroke patients and aspirin-free controls.
      Although aggregation was slightly higher, 12 out of the 14 receptor analyses,
      were surprisingly lower in the post-stroke cohort. Aspirin-treated patients
      exhibited highly significant inhibition of epinephrine-induced aggregation
      (p=0.0001), prolongation of the closure time (p=0.03), and reduction of the
      aspirin reactive units (p=0.02) measured by the Ultegra device. In addition,
      surface platelet expression of thrombospondin (p=0.001), GPIIb/IIIa activity
      (p=0.04), P-selectin (p=0.03), CD40-ligand (p=0.04), CD165 (p=0.02), the
      formation of the platelet-monocyte aggregates (p=0.01), and intact epitope of PAR
      1 thrombin receptor (p=0.03) were significantly lower in the aspirin-treated
      group. CONCLUSIONS: Platelets are not activated in aspirin-free patients after
      ischemic stroke. Platelet function is significantly inhibited in those treated
      with aspirin when compared with healthy subjects with risk factors for vascular
      disease. Bleeding complications and hemorrhagic transformations after aggressive
      antiplatelet regimens could be related to the decreased or normal baseline
      platelet characteristics in such patients. Further analysis of platelet
      heterogeneity and its clinical significance remains to be determined in
      randomized trials.

PMID- 15140584
TI  - Low-dose oral vitamin K is safe and effective for outpatient management of
      patients with an INR>10.
AB  - BACKGROUND: Low-dose oral vitamin K effectively returns an international
      normalized ratio (INR) between 4.5 and 10.0 to an INR of 2.0-3.0 within 24 h in
      about 70% of patients. However, the efficacy of oral vitamin K for the treatment
      of higher INR values has only been studied in one small randomized trial.
      Treatment of markedly prolonged INR values with low-dose oral vitamin K is
      attractive because it has the potential to greatly simplify the management of
      such patients. METHODS: In our tertiary care anticoagulation clinic patients with
      an INR of more than 10 were managed as outpatients with simple warfarin
      withdrawal and, where feasible, low-dose (2 mg) oral vitamin K. Only patients
      with additional complications such as bleeding or unexplained symptoms were
      admitted to hospital. RESULTS: Eighty-five patients had 89 episodes of an INR
      value of more than 10.0. Fourteen patients were admitted to the hospital for
      management. In the other 75 episodes patients were managed as outpatients by
      warfarin withdrawal. In 24 episodes patients did not receive vitamin K. In 51
      episodes patients were also given oral vitamin K. None of the patients given oral
      vitamin K experienced bleeding requiring medical intervention (95% confidence
      interval (CI) 0-6%). In contrast there were three clinically important bleeding
      episodes amongst the patients managed with simple warfarin withdrawal (95% CI 0
      34%). Patients given vitamin K were also more likely to have an INR<5 by day 3
      than those managed by withdrawal of warfarin alone. Two patients admitted to
      hospital and given intravenous vitamin K at higher doses became temporarily
      refractory to anticoagulation while there were no such complications in those
      treated with low-dose oral vitamin K. CONCLUSION: Low-dose (2 mg) oral vitamin K,
      coupled with temporary warfarin discontinuation, appears to be a safe and
      effective treatment for severe warfarin associated coagulopathy in non-bleeding
      patients.

PMID- 15140585
TI  - Activation of blood coagulation in patients undergoing postoperative blood
      salvage and re-infusion of unwashed whole blood after total knee arthroplasty.
AB  - BACKGROUND: Perioperative blood salvage is commonly used in cardiovascular
      surgery and has been more recently introduced in major orthopedic surgery.
      Limited information is available on the influence of re-infused whole blood on
      the hemostatic system in orthopedic patients. MATERIALS AND METHODS: The aim of
      this study was to assess whether perioperative salvage and re-infusion of
      unwashed whole blood is associated with an activation of blood coagulation in
      patients undergoing total knee replacement. Consecutive patients receiving re
      infusion were included in the study (n=13). Patients undergoing total knee
      replacement without perioperative blood salvage and re-infusion served as
      controls (n=6). In patients receiving re-infusion thrombin-antithrombin complexes
      (TAT), plasmin-antiplasmin complexes (PAP) and fibrinogen were assayed at the
      following times: before surgery (baseline), immediately before re-infusion (T0),
      immediately (T1), 2 h (T2) and 24 h (T3) after the end of re-infusion. In control
      patients blood samples were drawn at the average times corresponding to each of
      the sampling time in the patients receiving re-infusion. The first post-surgery
      LMWH dose was given within 12 h after surgery. RESULTS: TAT and PAP increased
      after surgery both in patients receiving re-infusion and controls. An increase of
      TAT and PAP was observed immediately after re-infusion with respect to baseline
      (TAT 513.1 +/- 259.1 microg/l vs. 5.3 +/- 4.9, p<0.0001; PAP 7408.0 +/- 1892.1
      microg/l vs. 461.4 +/- 217.1, p<0.0001) and to controls (TAT 60.4 +/- 26.9
      microg/l, p=0.002; PAP 2208.3 +/- 1446.4 microg/l, p<0.001). The levels of TAT
      and PAP in patients receiving re-infusion remained high at 2 h after re-infusion
      compared to those of the controls (TAT 124.1 +/- 38.3 microg/l vs. 38.08 +/-
      18.9, p=0.016; PAP 5690.7 +/- 1435.5 microg/l vs. 1613.9 +/- 706.0, p<0.001) and
      decreased 24 h thereafter. Fibrinogen level was lower in patients receiving re
      infusion compared to controls. CONCLUSIONS: Whole blood re-infusion is associated
      with an activation of blood coagulation in patients undergoing total knee
      replacement. The clinical relevance of this activation has to be tested in
      prospective studies with adequate sample size.

PMID- 15140586
TI  - The effect of a promoter polymorphism in the heme oxygenase-1 gene on the risk of
      ischaemic cerebrovascular events: the influence of other vascular risk factors.
AB  - Heme oxygenase-1 (HO-1) has been demonstrated to exert potent anti-oxidant and
      anti-inflammatory effects in the context of atherosclerotic vascular disease, and
      therefore was referred to as a potential vascular protective factor. A (GT)n
      dinucleotide repeat polymorphism in the HO-1 promoter has been shown to modulate
      HO-1 gene expression. Short (<25) GT repeats were associated with HO-1 up
      regulation, and therefore may influence susceptibility to ischaemic vascular
      events. We investigated the association of HO-1 repeat length with the risk of
      cerebrovascular events in a case control study and assessed possible
      interrelations with vascular risk factors. We determined the number of GT repeats
      in the HO-1 promoter in 399 patients with ischaemic cerebrovascular events and
      398 healthy controls and compared the frequencies of short (<25) repeat (class S)
      and long (> or =25) repeat (class L) alleles after adjustment for potentially
      confounding factors. Genotype distributions of S/S, S/L and L/L in patients were
      9.8% (n=39), 45.1% (n=180) and 45.1% (n=180), which was similar to the
      distribution in controls with 11.5% (n=46), 44.5% (n=177) and 44.0% (n=175). In
      the presence of vascular risk factors, the HO-1 genotype became functionally
      relevant: in patients without hyperlipidemia the S/S genotype exerted a
      protective effect on the development of ischaemic cerebrovascular events (OR 0.2;
      95% CI 0.1-0.6), while this effect was no longer present in hyperlipidemic
      patients. Short (<25 GT) repeats in the HO-1 gene promoter confer a reduced risk
      for cerebrovascular events in individuals with normal plasma lipid levels. This
      may explain controversial findings in different populations.

PMID- 15140587
TI  - Glycoprotein IIb/IIIa inhibition enhances platelet nitric oxide release.
AB  - INTRODUCTION: Platelet aggregates form by fibrinogen binding to the membrane
      receptor glycoprotein IIb/IIIa (GPIIb/IIIa). While GPIIb/IIIa inhibitors block
      fibrinogen-platelet binding, stimulation of other functionally important platelet
      receptors may still occur. Blocking the GPIIb/IIIa receptor prevents platelet
      aggregation but not activation and the subsequent effect on other platelet
      pathways is largely unknown. MATERIALS AND METHODS: As activated platelets
      release reactive oxygen species that may influence thrombosis or vascular
      function, the effect of GPIIb/IIIa inhibitors on the platelet release of nitric
      oxide (NO) and superoxide was determined using an electrochemical detector and
      luminescence, respectively. Location of relevant platelet proteins and the
      interaction between platelets and leukocytes in the presence or absence of
      GPIIb/IIIa inhibition was determined. RESULTS: Although incubation with
      GPIIb/IIIa inhibitors completely abolished platelet aggregation, stimulation
      dependent NO release was significantly enhanced. Superoxide is known to alter the
      bioavailability of NO, and its contribution to the GPIIb/IIIa dependent increase
      in NO release was determined. In the presence of GPIIb/IIIa inhibitors, platelet
      superoxide release was significantly decreased. Preincubation with GPIIb/IIIa
      inhibitors also modified aggregation induced membrane translocation of the
      platelet proteins, endothelial NO synthase (eNOS) and NADPH oxidase (p67phox and
      p47phox), known to contribute to the generation of NO and superoxide,
      respectively. In the presence of leukocytes, abciximab incubation led to enhanced
      NO release and attenuated superoxide generation. CONCLUSION: These observations
      suggest that the pharmacological effects of GPIIb/IIIa antagonists on platelet
      function, apart from inhibition of aggregation, may contribute to their efficacy.

PMID- 15140588
TI  - The inhibitory effects of Silso-San-Gami on atherosclerosis in KHC rabbits.
AB  - Silsosangami is a dried decoction of a mixture of seven Korean herbal medicines,
      consisting of Typhae pollen, Pteropi faeces, Paeoniae radicis rubra, Cnidii
      rhizoma, Persicae semen, Carthami flos, and Curcumae tuber. The inhibitory effect
      of this traditional herbal medicine, Silsosangami-water extract (SSG), on the
      progression of the atherosclerotic diseases was examined using the spontaneous
      familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi
      hypercholesterolemic (KHC) rabbits. Changes in blood chemistry, pathology and low
      density lipoprotein (LDL) oxidation were measured in a control group and a SSG
      administrated group. In the control group, the area of atheromatous aortic
      plaques progressed between 4 weeks (30.43%) and 8 weeks (47.48%). This progressin
      of atherosclerotic disease was not observed in the SSG-treated group between 4
      weeks (22.65%) and 8 weeks (23.23%). Antioxidative effects on LDL were observed
      in the SSG group at 12 and 14 weeks. SSG improved hypercholestrolemia in the KHC
      rabbits. These results suggest that SSG has inhibitory effects on the development
      of atheromatous plaques in spontaneous FH model rabbits. The antioxidative
      effects of SSG on LDL appear to be the source of the beneficial effects observed
      in this study.

PMID- 15140589
TI  - A small fraction of dermatan sulfate with significantly increased anticoagulant
      activity was selected by interaction with the first complement protein.
AB  - Dermatan sulfate (DS) is a member of the family of structurally complex,
      sulfated, linear heteropolysaccharides called glycosaminoglycans (GAGs). It has a
      similar structure to heparin and heparan sulfate (HS), but with
      acetylgalactosamine replacing glucosamine, and the uronic acid moiety, mainly
      iduronic, joined 1-->3 to the hexosamine. We are studying the relationships
      between structure and activities of dermatan sulfate, in particular those
      associated with the thrombin inhibition mediated by heparin cofactor II (HCII).
      As we have demonstrated with heparin, a small fraction of dermatan sulfate was
      isolated by precipitation with the first component of the complement system,
      under very specific conditions of low ionic strength, and the presence of calcium
      ions. The sulfate content and the anticoagulant activity of the dermatan sulfate
      fraction isolated in the precipitate were three and four times greater
      respectively than the starting material. Our in vivo studies showed that this
      fraction has threefold higher thrombolytic activity than the DS. All these
      results suggest that this fraction could be used as a therapeutic agent for
      thrombi dissolution.

PMID- 15140590
TI  - Two monoclonal antibodies to D-dimer-specific inhibitors of fibrin
      polymerization.
AB  - D-dimer of human fibrin was used as antigen to obtain monoclonal antibodies
      (mAbs). We have obtained 16 hybridomas producing mAbs of different specificity.
      Only two of these mAbs inhibited fibrin polymerization. They are of the IgG
      class. One mAb (II-4d) inhibited fibrin polymerization to 100% and another (II
      3b) to 60% at a molar ratio mAb/fibrin=1.0. Fab-fragments of these mAbs inhibited
      fibrin polymerization completely at the same molar ratio. The epitopes for the
      mAbs studied are situated in the NH2-terminal part of the gamma-chain in fibrin D
      domain. Electron microscopy showed that fibrin was in monomeric form in the
      presence of these mAbs or their Fab-fragments. Thus, these mAbs stop the initial
      step of fibrin polymerization, i.e. protofibril formation. Only one site of
      protofibril formation is known now in COOH-terminal half of the D-domain gamma
      chain named "a" site, which is complementary to the "A" site in the central E
      domain of fibrin molecule. Our experiment with immobilized GPRP showed that the
      "a" site in fibrin D-fragment preserved its binding activity to GPRP when the D
      fragment was complexed with mAbs-inhibitors of fibrin polymerization. Thus, these
      two mAbs inhibit fibrin polymerization not by blocking the sites "a" but either
      by blocking another (not "a") specific site in D-domain or by steric hindrance of
      highly organized fibrin polymerization process.

PMID- 15140591
TI  - A collaborative study to establish a Korean Standard for factor VIII:C
      concentrate.
AB  - BACKGROUND AND OBJECTIVES: A collaborative study among five laboratories
      including three manufacturers and two national control laboratories was carried
      out to evaluate the suitability of a candidate to serve as a Korean Standard for
      factor VIII:C concentrate. MATERIALS AND METHODS: Two approaches were attempted
      to determine the potency of this candidate. The one is a one-stage clotting assay
      and the other is a chromogenic assay. To achieve acceptable precision and
      accuracy, the following recommendations by the International Society on
      Thrombosis and Haemostasis were adopted in the assays, e.g., pre-dilution of
      samples in factor VIII (FVIII)-deficient plasma, inclusion of 1% albumin in the
      dilution buffer and calibration against the sixth International Standard for the
      blood coagulation factor VIII:C concentrate, coded 97/616. RESULTS: The data
      collected within each laboratory and among laboratories for both assays employed
      here were in good agreements in the calibration of the candidate preparation
      against the International Standard. The overall potencies by the one-stage
      clotting assay and the chromogenic assay, however, showed recognizable
      differences between them. Each differed from each other in that the potency
      obtained from chromogenic assay was approximately 17% lower than that from one
      stage clotting assay. The estimated geometric mean value obtained from the one
      stage clotting assay was 8.4 international units (IU)/vial and that from the
      chromogenic assay was 6.7 IU/vial. CONCLUSIONS: Based on the results of this
      collaborative study, the candidate standard is judged to be suitable to serve as
      a Korean National Standard for factor VIII:C concentrate.

PMID- 15140592
TI  - Blood coagulation factors in the black headed vulture (Coragyps atratus), a
      potential animal model for the study of haemostasis.

PMID- 15140593
TI  - Ovarian hypercytolipidemia induced by obese (ob/ob) and diabetes (db/db)
      mutations: basis of female reproductive tract involution II.
AB  - The diabetes (db/db) and obese (ob/ob) genotype mutations induce a progressive,
      hypercytolipidemic condition within the ovarian compartments of the female
      reproductive tract that results in sterility and premature organ involution in
      C57BL/KsJ mice. The current studies focus on the ultrastructural changes that
      occur within the ovarian interstitial, thecal, and follicular granulosa cell
      layers during the progressive expression of these mutations which promote tissue
      cytolipidemia-induced organoinvolution. Control (normal: +/?), diabetes (db/db),
      and obese (ob/ob) genotype groups were prepared for high resolution light (HRLM)
      and transmission electron microscopic (TEM) analysis of ovarian tissue samples
      collected from 4 (young)- to 20 (aged)-week-old mice, allowing for the
      progressive influences of the mutational aberrations on tissue structure to be
      evaluated. Compared to controls, both (ob/ob) and (db/db) mutations induced a
      dramatic increase in ovarian interstitial, thecal and follicular granulosa
      cytolipid vacuole accumulations, which increased in density between 4 and 20
      weeks of age. Initially, lipid vacuoles aggregated in the interstitial and thecal
      regions of ovarian follicles in response to the hyperglycemic
      hypertriglyceridemic metabolic conditions typical of both (ob/ob) and (db/db)
      groups. Progressive cytoplasmic movement of the lipid pools established a
      perinuclear isolation from associated cytoplasmic organelles. Progressive lipid
      accumulations forced cytoplasmic organelles to peripheral cell compartments and
      altered the follicular cell profile towards that of adipocyte-like entities
      relative to controls. The progressive hypercytolipidemia-induced alterations in
      cell structure disrupted normal tissue continuity, which culminated in premature
      ovarian organo-involution and female reproductive sterility.

PMID- 15140594
TI  - Morphological characterization of Anticarsia gemmatalis M nucleopolyhedrovirus
      infection in haemocytes from its natural larval host, the velvet bean caterpillar
      Anticarsia gemmatalis (Hubner) (Lepidoptera: Noctuidae).
AB  - For a better understanding of virus x host interactions, transmission electron
      microscopy was used to characterize the intrahaemocoelic infection of Anticarsia
      gemmatalis larval haemocytes by A. gemmatalis M nucleopolyhedrovirus (AgMNPV). At
      12 h post-infection (h p.i.), we observed nuclear hypertrophy, budded virus
      assembling, and protrusion towards the cytoplasm, virion envelopment, and
      accumulation of fibrillar aggregates in the cytoplasm. Around 24 h p.i.,
      fibrillar aggregates also appeared inside nuclei of infected cells. By 48 h p.i.,
      virogenic stroma and polyhedra were visualised in nuclei and at 72 h p.i.,
      widespread infection in haemocytes was observed. Cell remnants and free polyhedra
      were phagocytosed by granular haemocyte 1 and plasmatocytes. Entire cells were
      phagocytosed only by plasmatocytes. Necrosis of infected cells was quite common,
      suggesting a putative cytotoxic response. Granular haemocyte 1 presented a more
      exuberant protrusion of budded viruses in comparison to other haemocytes. All
      types of haemocytes were shown to be infected, and the intense virus replication
      in some of these cells reveals the importance of haemolymph for AgMNPV spread in
      its natural host, a critical factor for permissiveness.

PMID- 15140595
TI  - Stabilization of calpain large subunits by overexpression of truncated calpain
      small subunit in L8 myoblasts.
AB  - The objectives were to investigate the function of the small subunit in the
      calpain system by expression of the autolytic form of this subunit in L8
      myoblasts. Rat post-autolysis small subunit (21 kDa) cDNA expression plasmid was
      transfected into L8 myoblasts and selected by G418 containing medium. The
      concentrations of cytosolic micro-calpain in transfected cells, SS2 and SS3, were
      found to be 15.7 and 17.3% higher than that in L8Neo control cells, and the
      concentrations of cytosolic m-calpain in SS2 and SS3 cells were 23.3 and 16.6%
      higher than that in control cells (L8Neo). The half-life of micro-calpain in SS3
      cells (36.5 h) was longer than that in L8Neo cells (32.4 h), while the half-life
      of m-calpain in SS3 cells (40.1 h) was longer than that in L8Neo cell (37.5 h).
      These results indicated that the expression of truncated small subunit increased
      the stability of micro- and m-calpain large subunits in cytosol.

PMID- 15140596
TI  - Musculature of an illoricate predatory rotifer Asplanchnopus multiceps as
      revealed by phalloidin fluorescence and confocal microscopy.
AB  - The pattern of muscles in the actively swimming predatory rotifer Asplanchnopus
      multiceps is revealed by staining with tetramethyl-rhodamine isothiocyanate
      (TRITC)-labelled phalloidin and confocal scanning laser microscopy (CSLM). The
      major components of the musculature are: prominent semicircular muscles of the
      corona; paired lateral, dorsal and ventral retractors in the trunk; a network of
      six seemingly complete circular muscles and anastomosing longitudinal muscles in
      the trunk; two short foot retractors, originating from a transverse muscle in the
      lower third of the trunk. The sphincter of the corona marks the boundary between
      the head and the trunk. The muscular patterns in rotifers with different
      lifestyles differ clearly, therefore, the muscular patterns seem to be determined
      by the mode of locomotion and feeding behaviour.

PMID- 15140597
TI  - Autoschizis: a new form of cell death for human ovarian carcinoma cells following
      ascorbate:menadione treatment. Nuclear and DNA degradation.
AB  - Microscopic aspects, densitometric evaluation of Feulgen-stained DNA, and gel
      electrophoresis of total DNA have been used to elucidate the effects of 1, 2, and
      3 h VC (ascorbic acid), VK3 (menadione), and combined VC:VK3 treatments on the
      cellular and nuclear morphology and DNA content of a human ovarian carcinoma cell
      line (MDAH 2774). Optical densitometry showed a significant decrease in cancer
      cell DNA content directly related to VC and VC:VK3 treatments while VK3 and
      VC:VK3 treated cells exhibited cytoskeletal changes that included self-excision
      of cytoplasmic pieces with no membranous organelles. Nuclei decreased in size and
      exhibited poor contrast consistent with progressive decondensation of their
      chromatin. Degraded chromatin was also detected in cytoplasmic autophagosomes.
      Nucleoli segregated their components and fragmented into small pieces. Gel
      electrophoretic analysis of total DNA revealed evidence of generalized DNA
      degradation specific to treated tumor cells. These results are consistent with
      previous observations [Scanning 20 (1998a) 564; Ultrastruct. Pathol. 25 (2001b)
      183; J. Histochem. Cytochem. 49 (2001) 109] which demonstrated that the VC:VK3
      combination induced autoschizic cell death by a series of cytoplasmic excisions
      without organelles along with specific nuclear ultrastructural damage.

PMID- 15140598
TI  - Fine structure of the Nassonow's gland in the neotenic endoparasitic of female
      Xenos vesparum (Rossi) (Strepsiptera, Insecta).
AB  - Nassonow's gland consists of a number of cells with ducts that open on to the
      ventral surface of the brood canal in the cephalothoracic region of a neotenic
      female strepsipteran. The structural organization of the gland is reminiscent of
      the class 3 of the epidermal gland cells as defined by Noirot and Quennedey [Ann.
      Rev. Entomol. 19 (1974) 61], which consists of secretory and duct forming cells.
      The ultrastructure of the Nassonow's gland is described in female Xenos vesparum
      (Rossi) parasitic in the social wasp Polistes dominulus Christ. The large
      secretory cells are clustered in groups of three to four, rich in smooth
      endoplasmic reticulum and produce a secretion made up of lipids. In young
      females, just before mating, the ultrastructure of the cells and their inclusions
      indicate that they are active. In old-mated females the Nassonow's gland
      degenerates. Microvilli line an extracellular cavity and there are pores present
      in the irregularly thick cuticle of the efferent duct. The small duct forming
      cells, intermingle with epidermal cells, overlap secretory cells and produce a
      long efferent duct, the cuticle of which becomes thick close to its opening in
      the brood canal. Nassonow's gland could be the source of a sex pheromone, which
      might be capable of attracting the free-living male to a permanently
      endoparasitic female.

PMID- 15140599
TI  - The etiology of syringomyelia in association with lesions of the foramen magnum.

PMID- 15140600
TI  - The pathogenesis of syringomyelia associated with lesions at the foramen magnum:
      a critical review of existing theories and proposal of a new hypothesis.
AB  - Syringomyelia is frequently accompanied by an extramedullary lesion at the
      foramen magnum, particularly a Chiari I malformation. Although syringomyelia
      associated with foramen magnum obstruction has characteristic clinical,
      radiological, and neuropathological features, its pathogenesis remains unclear.
      Currently prevalent hydrodynamical theories assert that obstruction of the
      subarachnoid space at the foramen magnum interferes with flow of cerebrospinal
      fluid (CSF) between the spinal and the intracranial subarachnoid compartments. As
      a result, spinal CSF is driven into the spinal cord through the perivascular
      spaces to form a syrinx. These theories are implausible biophysically because
      none postulates a pump adequate to drive fluid through these spaces. None of the
      theories can explain why syrinx pressure is higher than CSF pressure; why
      extensive gliosis, edema, and vascular wall thickening regularly occur; and why
      the composition of syrinx fluid is not identical with that of CSF. A new theory
      of pathogenesis is proposed to address these difficulties. In the presence of
      subarachnoid obstruction at the foramen magnum, a variety of activities, such as
      assuming the erect posture, coughing or straining, and pulsatile fluctuations of
      CSF pressure during the cardiac cycle, produce transiently higher CSF pressure
      above the block than below it. There are corresponding changes in transmural
      venous and capillary pressure favoring dilation of vessels below the block and
      collapse of vessels above the block. The spatially uneven change of vessel
      caliber produces mechanical stress on the spinal cord, particularly caudal to the
      block. The mechanical stress, coupled with venous and capillary dilation,
      partially disrupt the blood-spinal cord barrier, allowing ultrafiltration of
      crystalloids and accumulation of a protein-poor fluid. The proposed theory is
      consistent with the neuropathological findings in syringomyelia and with the
      pressure and composition of syrinx fluid. It also accounts for the prolonged
      course of syringomyelia and its aggravation by cough, strain, and assumption of
      an erect posture. It contributes to understanding the low incidence and the
      morphology of syringobulbia. It explains the poorly understood presentation of
      foramen magnum meningiomas with symptoms of a mid- to low-cervical myelopathy.
      The theory also affords an understanding of the late recurrence of symptoms in
      children with hydromyelia who are treated with a ventricular shunt.

PMID- 15140601
TI  - Time course of NAA T2 and ADC(w) in ischaemic stroke patients: 1H MRS imaging and
      diffusion-weighted MRI.
AB  - BACKGROUND AND PURPOSE: Proton spectroscopy and quantitative diffusion-weighted
      imaging (DWI) were used to investigate the pertinence of N-acetyl aspartate (NAA)
      as a reliable marker of neuronal density in human stroke. METHODS: The time
      courses of tissue water apparent diffusion coefficient (ADC(w)) and metabolite T2
      were investigated on a plane corresponding to the largest area of cerebral
      infarction, within and outside the site of infarction in 71 patients with a large
      cortical middle cerebral artery territory infarction. RESULTS: Significant
      reductions are seen in NAA T2 deep within the infarction during the period
      comprised between 5 and 20 days postinfarction; the relaxation times appearing to
      normalise several months after stroke. After an acute reduction in ADC(w), the
      pseudonormalisation of ADC(w) occurs at 8-12 days after the ischaemic insult. The
      minimum in N-acetyl aspartate T2 relaxation times and the pseudonormalisation of
      ADC(w) appear to coincide. CONCLUSIONS: The data suggest that modifications in
      the behaviour of the observed proton metabolites occur during the period when the
      vasogenic oedema is formed and cell membrane integrity is lost. For this reason,
      NAA may not be a reliable marker of neuronal density during this period.

PMID- 15140602
TI  - The spectrum of antineuronal autoantibodies in a series of neurological patients.
AB  - The aim of the present study is to identify the range of neurological disorders
      expressing antineuronal antibodies, evaluate the number of different patterns of
      reactivity that can be detected, and analyse the contribution of these studies to
      the identification of subgroups of patients. The records of 882 patients were
      reviewed and their sera and cerebrospinal fluids tested for antineuronal
      antibodies. Patients were initially divided into four groups according to
      suspected clinical diagnosis. Autoantibodies were detected by
      immunohistochemistry, Western blot of gradient-separated neuronal and recombinant
      proteins and by RIA. Cerebellar degeneration and sensory neuropathies were the
      most common neurological disorders in which paraneoplastic-related anti-neuronal
      antibodies were detected. However, in addition to PCA1/anti-Yo and ANNA1/anti-Hu
      antibodies, we found other reactivities in six patients with cerebellar
      degeneration: anti-GAD in three females and atypical in the other cases. The
      widest range of different anti-neuronal antibodies was detected in patients with
      peripheral sensory neuropathy. Few patients with Stiff-Person syndrome, temporal
      lobe epilepsy and myoclonus harboured anti-GAD antibodies. Atypical antibodies
      were detected in single cases with motor neuron disorder and multiple system
      atrophy. No anti-neuronal antibodies were detected in patients with neurological
      complications of connective tissue disorders other than Sjogren's syndrome, or in
      neurological diseases other than motor neuron disease and multiple system
      atrophy. Our study shows that the spectrum of neurological disorders in which
      anti-neuronal antibodies can be detected is wider than previously thought. In
      addition, we found patterns of neuronal staining and Western blot reactivity that
      differed from those so far reported. This may permit identification of subgroups
      of patients in whom strategies directed at removing and/or suppressing antibody
      production could be of some benefit.

PMID- 15140603
TI  - Clinical and neuroradiologic features of 39 consecutive cases of West Nile Virus
      meningoencephalitis.
AB  - BACKGROUND: West Nile Virus (WNV) is a flavivirus WNV that has spread westwards
      across North America in recent years. It can cause a febrile illness and
      infection of the central nervous system, which is associated with poor outcome.
      METHODS: We retrospectively studied the clinical and neuroradiologic features of
      39 consecutive patients admitted during summer of 2002 that had IgM in the
      cerebrospinal fluid positive for WNV. RESULTS: Fever, headache and altered
      mentation were predominant clinical features. Clinically significant involvement
      of lower motor neurons was seen in few cases. Magnetic resonance imaging (MRI) of
      the brain did not show changes attributable to meningitis or encephalitis except
      for one case of subcortical signal abnormalities. Unfavorable prognostic factors
      are old age, decreased level of alertness and elevated serum creatinine.
      CONCLUSIONS: Encephalopathic presentations, with or without additional
      neurological focality, dominated this series. Fever and meningitic signs are
      often absent. Involvement of lower motor neurons was uncommon. Given the paucity
      of positive findings, the value of MRI to support the diagnosis of WNV
      meningoencephalitis is limited.

PMID- 15140604
TI  - Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from
      Parkinson patients.
AB  - Several lines of evidence suggest an impairment of mitochondrial function in the
      brain of patients with Parkinson's disease (PD). However, the presence of a
      detectable mitochondrial defect in extracerebral tissue of these patients remains
      a matter of dispute. Therefore, we investigated mitochondrial function in
      fibroblasts of 18 PD patients applying biochemical micromethods. Putative
      beneficial effects of coenzyme Q(10) (CoQ(10)), a potent antioxidant, on the
      mitochondrial function of skin fibroblast cultures were evaluated. Applying
      inhibitor titrations of the mitochondrial respiration to calculate flux control
      coefficients of respiratory chain complexes I and IV, we observed deficiencies of
      both complexes in cultivated skin fibroblasts of PD patients. Cultivation of
      fibroblasts in the presence of 5 microM CoQ(10) restored the activity of impaired
      respiratory chain complexes in the fibroblast cultures of 9 out of 18 PD
      patients. Our data support the presence of a generalised mitochondrial defect in
      at least a subgroup of patients with PD that can be partially ameliorated in
      vitro by coenzyme Q(10) treatment.

PMID- 15140605
TI  - Dynamic cerebral autoregulation is impaired in glaucoma.
AB  - OBJECTIVES: Autonomic and endothelial dysfunction is likely to contribute to the
      pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma
      (POAG). Although there is evidence of vasomotor dysregulation with decreased
      peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been
      evaluated. The aim of our study was to assess dynamic CA in patients with NPG and
      POAG. MATERIALS AND METHODS: In 10 NPG patients, 11 POAG patients and 11
      controls, we assessed the response of cerebral blood flow velocity (CBFV) to
      oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz.
      CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz
      oscillations in MAP and CBFV. RESULTS: 0.1 Hz spectral powers of MAP did not
      differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients
      with NPG (5.68+/-1.2 cm(2) s(-2)) and POAG (6.79+/-2.1 cm(2) s(-2)) than in
      controls (2.40+/-0.4 cm(2) s(-2)). Furthermore, the MAP-CBFV gain was higher in
      NPG (2.44+/-0.5 arbitrary units [a.u.]) and POAG (1.99+/-0.2 a.u.) than in
      controls (1.21+/-0.1 a.u.). CONCLUSION: Enhanced transmission of oscillations in
      MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and
      might contribute to an increased risk of cerebrovascular disorders in these
      diseases.

PMID- 15140606
TI  - Validation of the Oxfordshire Community Stroke Project syndrome diagnosis derived
      from a standard symptom list in acute stroke.
AB  - BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification allows
      distinction of stroke subtypes with different prognosis. OCSP classification
      inferred from clinical signs filled out on patient entry forms has been used to
      facilitate subgroup analysis in clinical trials. However, such procedure has not
      been validated against clinical diagnosis. In preparation for an acute stroke
      trial, we set out to perform such a validation. METHODS: An OCSP syndrome
      diagnosis of 194 acute stroke patients in four hospitals was made within 24 h
      using a standard list with neurological signs, to be filled out by a stroke
      physician or neurological resident on duty. This was compared with OCSP diagnosis
      within 2 days of stroke onset by a (blinded) stroke neurologist ("gold
      standard"). RESULTS: The proportion of the OCSP syndromes was quite similar
      between standard list and clinical judgement. Sensitivity, specificity, positive
      and negative predictive values were respectively: LACS: 0.76, 0.88, 0.72, 0.90;
      TACS: 0.63, 0.93, 0.62, 0.88; PACS: 0.62, 0.76, 0.63, 0.75; POCS: 0.50, 0.98,
      0.60, 0.97. Kappa for agreement was 0.63 (LACS), 0.37 (PACS), 0.50 (TACS). Neuro
      imaging falsified stroke subtype diagnosis in 40 cases (20.6%) diagnosed using
      the standard list, and 42 (21.6%) diagnosed by stroke neurologists. CONCLUSION: A
      standard list-derived stroke syndrome diagnosis may be used as a clinical test to
      make an OCSP syndrome diagnosis in acute stroke. The use of such list in acute
      stroke trials may facilitate uniformity in early stroke subtype diagnosis.
      However, to increase such uniformity, ancillary methods such as acute MRI should
      be evaluated.

PMID- 15140607
TI  - Thy1 expression in the brain is affected by iron and is decreased in Restless
      Legs Syndrome.
AB  - Thy-1 is a cell adhesion molecule that plays a regulatory role in the vesicular
      release of neurotransmitters. The objective of this study is to examine the
      relationship between iron status and Thy1 expression in neuronal systems of
      varying complexity. Pheochromocytoma cell (PC12) cells were used to explore
      whether there was a direct relation between cellular iron status and Thy1
      expression. Iron chelation significantly decreased expression of Thy1 in PC12
      cells in a dose and time dependent manner. Transferrin receptor expression was
      increased with iron chelation demonstrating that a global decrease in protein
      synthesis could not account for the Thy1 changes. We also examined brain
      homogenates from adult rats that were nursed by dams on an iron deficient (ID)
      diet and found a significant decrease in Thy1 compared to control rats. Finally,
      the substantia nigra from individuals with Restless Legs Syndrome reportedly has
      lower than normal amounts of iron. Therefore, we examined this brain region from
      individuals with the clinical diagnosis of primary Restless Legs syndrome (RLS)
      and found the concentration of Thy1 was less than half that of controls. The
      results of these studies support the novel concept that there is a relationship
      between Thy1 and iron and point to a novel mechanism by which iron deficiency can
      affect brain function. They also indicate a possible mechanism by which iron
      deficiency compromises dopaminergic transmission in RLS, providing a potentially
      important link between decreased brain iron and the responsiveness to levodopa
      and iron supplementation treatment in RLS.

PMID- 15140608
TI  - Long-latency reflexes in patients with Behcet's disease.
AB  - OBJECTIVE: Recent studies demonstrate that the subclinical involvement of motor
      pathways is frequently observed in patients with Behcet's disease (BD). Long
      latency reflexes (LLR) provide information about the continuity of both ascending
      and descending neural pathways. Our aim was to evaluate the utility of LLR and
      somatosensory-evoked potentials (SEP) in demonstrating subclinical neural
      involvement in patients with BD. METHODS: Twenty-nine patients with BD were
      studied by means of SEP and LLR. Bilateral median nerve SEPs and LLRs evoked by
      electrical stimulation of both median nerves were recorded. The latency of second
      component of LLR (LLR2), the duration of LLR2-HR (Hoffmann reflex, spinal reflex
      component of LLR) interval, peak to peak amplitude of LLR2 and the amplitude
      ratio of LLR2/HR were analyzed. The data obtained from patients were compared
      with those of 20 control subjects. RESULTS: LLR2 latencies and the durations of
      LLR2-HR interval were significantly prolonged in patients with BD (p=0.001 for
      both parameters). Increased duration of LLR2-HR interval was the most frequent
      abnormality observed in the study (37.9%). CONCLUSION: Our findings suggest that
      LLR is a useful technique to demonstrate subclinical neural involvement in
      patients with BD.

PMID- 15140609
TI  - Persistent increase of matrix metalloproteinases in cerebrospinal fluid of
      tuberculous meningitis.
AB  - Matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by gelatin zymography
      and an enzyme-linked immunosorbent assay (ELISA) in a cerebrospinal fluid (CSF)
      from patients with tuberculous meningitis (n=24), acute aseptic meningitis (n=23)
      and the control (n=10). The MMP-2 and MMP-9 levels were significantly higher in
      the samples from the tuberculous meningitis patients than those from either the
      aseptic meningitis patients or the controls. In tuberculous meningitis, the
      patients with late neurologic complications had higher MMP-2 and MMP-9 levels
      than those without. The persistent increase in the MMP-2 and MMP-9 levels was
      associated with the development of complications following tuberculous
      meningitis. Inhibiting the MMPs may be an effective strategy for preventing or
      reducing the complications in tuberculous meningitis.

PMID- 15140610
TI  - Cerebral blood flow patterns in Binswanger's disease: a SPECT study using three
      dimensional stereotactic surface projections.
AB  - We investigated regional cerebral blood flow (rCBF) patterns in Binswanger's
      disease (BD) patients using single photon emission computed tomography (SPECT).
      SPECT data on 22 patients with BD were analyzed using three-dimensional
      stereotactic surface projections (3D-SSP) and were compared with those of 22
      patients with Alzheimer's disease (AD). rCBF patterns in patients with BD were
      different from those with AD. The BD group had greater CBF reduction in the
      frontal and anterior cingulate cortices, while the AD group had greater CBF
      reduction in the temporoparietal and posterior cingulate cortices. However, the
      rCBF pattern of each patient was more variable, and could be divided into three
      patterns: anterior cerebral hypoperfusion, posterior cerebral hypoperfusion, and
      diffuse cerebral hypoperfusion patterns. A distinct CBF reduction in the
      temporoparietal and/or posterior cingulate cortices, indistinguishable from the
      CBF pattern observed in AD, was demonstrated in 8 of 22 (36%) patients with BD,
      in particular there was bilateral hemispheric involvement with a diffuse
      hypoperfusion pattern. Although no pathological confirmation could be performed,
      some of the BD patients with CBF reduction in the posterior cerebral cortices may
      represent additional changes in the brain due to AD. In the future, a
      longitudinal study including pathology will be needed to determine whether these
      patients have coexisting AD pathology.

PMID- 15140611
TI  - Nonparaneoplastic limbic encephalitis with relapsing polychondritis.
AB  - Relapsing polychondritis (RP), which shows pain, swelling and destruction of the
      affected parts, is a rare autoimmune disorder affecting cartilage. We report a
      patient with RP that affected skull cartilage, who subsequently developed
      multifocal meningoencephalitis. The patient presented with severe recent memory
      disturbance, anxiety and moderate depression. MRI study showed bilateral median
      temporal lobe lesions including hippocampi and amygdaloidal bodies, abnormal
      findings that disappeared after treatment with high-dose steroids. This is
      thought to be the first case of RP presenting amnesic syndrome and mental
      disorder associated with nonparaneoplastic limbic encephalitis involving
      bilateral hippocampi and amygdaloidal bodies detected by MRI.

PMID- 15140613
TI  - Familial monomelic amyotrophy: a case report from India.
AB  - Monomelic amyotrophy (MMA) is a benign lower motor neuron disorder in the young
      with male preponderance. It is characterized by insidious onset and progressive
      weakness and wasting of a distal extremity over a few years followed by
      spontaneous arrest. The exact pathogenesis is unknown. It is predominantly a
      sporadic disorder but rarely familial forms have been documented. In this report,
      we describe the phenotype of a 21-year-old man and his mother who were diagnosed
      to have MMA. The index case presented with left upper limb weakness and wasting
      of 3 years duration while his mother had right upper limb amyotrophy and weakness
      of 34 years. A total of 190 patients were diagnosed to have MMA in our institute
      over the last 27 years and this is the first case of familial MMA.

PMID- 15140612
TI  - Decreased density of ganglia and neurons in the myenteric plexus of familial
      dysautonomia patients.
AB  - BACKGROUND: Familial dysautonomia (FD) is a hereditary disease of the autonomic
      and sensory nervous system. A prominent manifestation of FD is gastrointestinal
      dyscoordination, which contributes to the morbidity and mortality in FD. AIM: As
      the myenteric plexus is an essential factor in gastrointestinal motility control,
      we compared its morphology in appendices of FD patients and controls. METHODS:
      Appendices from FD patients (N=19) were obtained during surgery of fundoplication
      and gastrostomy; normal appendices (N=17) were obtained from patients suspected
      to suffer from acute appendicitis, in whom, however, the appendix was found to be
      normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and
      in a blinded manner examined under a light microscope for seven morphologic
      parameters: ganglionic density, neuronal density, ganglionic area, number of
      stained neurons per ganglion, nerve bundle width, ratio between nervous tissue
      area and total area, and neuronal area. RESULTS: Ganglionic density was 10.13 per
      mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was
      70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The
      other parameters were not different between the two groups. CONCLUSION: Densities
      of myenteric ganglia and neurons of FD patients were significantly lower than in
      controls. This deficiency may contribute to the pathogenesis of FD
      gastroenteropathy.

PMID- 15140614
TI  - Cognitive impairment in Behcet's disease patients without overt neurological
      involvement.
AB  - We investigated the prevalence of cognitive impairment in patients with Behcet's
      disease (BD) without overt neurological involvement. The influence of disease
      duration, disease activity, prednisone dosage, and anxiety and depression levels
      was evaluated. Twenty-six consecutive BD outpatients and 26 healthy controls
      matched for age, education and sex completed a comprehensive neuropsychological
      battery including tests of memory, visuospatial and constructional abilities,
      language, attention and psychomotor speed, non-verbal reasoning and executive
      functioning. The Hamilton scales for anxiety and depression were administered.
      Disease activity was assessed using the Behcet's Disease Current Activity Form
      (BDCAF). Compared to controls, BD patients were significantly impaired on tasks
      evaluating long-term verbal and non-verbal memory, and visuospatial skills. In
      addition, BD patients were significantly more anxious and depressed than
      controls. Cognitive impairment was evident in 46.1% of BD patients compared with
      none of control subjects (p<0.0001), with memory representing the cognitive
      domain most affected. Both high disease activity (OR 1.3, 95% CI 1.0-1.5, p<0.04)
      and high prednisone dosage (OR 1.3, 95% CI 1.0-1.7, p<0.03) were independently
      associated with cognitive impairment in BD after adjustment for demographic
      variables. Cognitive impairment, involving mainly memory functions, occurs
      frequently in BD patients. It may occur independently of clinically overt
      neurological involvement, and is more common in patients with an active disease
      and in those receiving prednisone.

PMID- 15140616
TI  - Wallerian degeneration: history and clinical significance.

PMID- 15140615
TI  - Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of
      PD.
AB  - OBJECTIVE: Cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy studies of
      patients with idiopathic Parkinson's disease (PD) found decreased uptake. Whether
      this decrease is associated with clinical severity as assessed by the Unified
      Parkinson's Disease Rating Scale (UPDRS) and the phenotypes of PD has not been
      determined. METHODS: Cardiac MIBG scintigraphy was performed on 34 patients with
      PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB),
      and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M)
      ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H-Y) stage
      and UPDRS. Patients were grouped in two phenotypes, tremor and postural
      instability gait difficulty (PIGD)-dominant groups based on UPDRS components.
      Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype
      were analyzed in each group. RESULTS: The early H/M ratio was significantly lower
      in patients with PD (1.45+/-0.207) than in the NCs (2.08+/-0.231), and in those
      with MSA (1.99+/-0.284), but not in those with DLB (1.29+/-0.0435). The delayed
      H/M ratio for PD (1.33+/-0.276) also was significantly decreased as compared to
      the ratios for NCs (2.17+/-0.286) and MSA (2.16+/-0.414) but not DLB (1.16+/
      0.0949). The early H/M ratio was significantly correlated with both UPDRS score
      and age at onset, whereas the delayed H/M ratio only was significantly correlated
      with age at onset. The PIGD-dominant group had significantly higher UPDRS scores
      and lower H/M ratios than the tremor-dominant group. CONCLUSION: Cardiac MIBG
      scintigraphy can be used to differentiate PD from MSA and NC, and to determine
      the disease severity and phenotypes of PD.

PMID- 15140617
TI  - The axotomy response.

PMID- 15140618
TI  - Wallerian degeneration as a window to peripheral neuropathy.

PMID- 15140619
TI  - Clinical electrophysiology and pathophysiology: lessons from studies in
      demyelinating neuropathies.

PMID- 15140620
TI  - Effector mechanisms in anti-MAG antibody-mediated and other demyelinating
      neuropathies.

PMID- 15140621
TI  - Impact of inflammatory disease on the nerve microenvironment.

PMID- 15140622
TI  - Diabetic neuropathy in type 1 and type 2 diabetes and the effects of C-peptide.

PMID- 15140623
TI  - Experimental models of painful diabetic neuropathy.

PMID- 15140624
TI  - Pathology and molecular genetics of inherited neuropathy.

PMID- 15140625
TI  - The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor
      on the expression of thymidine phosphorylase.
AB  - Thymidine phosphorylase (platelet-derived-endothelial-cell-growth-factor)
      catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose
      1-phosphate, activates 5'-deoxy-5-fluorouridine (5'DFUR) and inactivates
      trifluorothymidine (TFT). The effect of 5'DFUR and TFT with or without a specific
      thymidine phosphorylase inhibitor (TPI) on thymidine phosphorylase mRNA, protein
      expression and activity was studied, in three human colon cancer cell lines,
      WiDR, HT29 and Lovo exposed for 72 h at IC50 concentrations. In Lovo cells TFT
      plus TPI only increased thymidine phosphorylase-protein expression 1.7-fold;
      5'DFUR and TFT treatment increased thymidine phosphorylase mRNA levels 5- and 1.4
      fold, respectively. In WiDR cells, 5'DFUR plus TPI significantly decreased
      thymidine phosphorylase-protein. TFT and TFT plus TPI increased thymidine
      phosphorylase-protein 2- and 3-fold, respectively. TPI and 5'DFUR decreased
      thymidine phosphorylase-mRNA levels significantly. In HT29 cells, 5'DFUR and
      5'DFUR plus TPI decreased both thymidine phosphorylase-protein and thymidine
      phosphorylase-mRNA. In all cell lines 5'DFUR and TFT did not affect thymidine
      phosphorylase activity, but treatment with TPI (alone or in combination)
      eliminated thymidine phosphorylase activity. This demonstrated that regulation is
      drug and cell line dependent.

PMID- 15140626
TI  - Characterization of phorbol esters activity on individual mammalian protein
      kinase C isoforms, using the yeast phenotypic assay.
AB  - An alternative in vivo assay, based on growth inhibition of yeast expressing an
      individual mammalian protein kinase C (PKC) isoform (proportional to the degree
      of PKC activation), was used to characterize the activities of phorbol-12
      myristate-13-acetate (PMA) and its analogues on classical (alpha and betaI),
      novel (delta and eta) and atypical (zeta) PKC isoforms. Effects of PMA, 4alpha
      PMA, phorbol-12-myristate-13-acetate-4-O-methyl-ether (MPMA), phorbol-12
      monomyristate (PMM), phorbol-12,13-diacetate (PDA), phorbol-13-monoacetate (PA),
      phorbol-12,13-dibutyrate (PDB), phorbol-12,13-didecanoate (PDD) and 12
      deoxyphorbol-13-phenylacetate-20-acetate (dPPA), on growth of yeast expressing
      individual PKC isoforms was determined. PMA-induced growth inhibition on all
      isoforms tested (except on PKC-zeta). PDD and PDB presented an efficacy similar
      to PMA; the other PMA-analogues presented lower efficacies. MPMA and 4alpha-PMA
      stimulated growth of yeast expressing classical PKCs and reduced the PMA-induced
      growth inhibition, effects similar to those exhibited by the PKC inhibitors
      chelerythrine and R-2,6-diamino-N-[[1-(1-oxotridecyl)-2-piperidinyl]methyl]
      hexanamide dihydrochloride (NPC 15437). This study reveals that phorbol esters
      differ on their potency to activate a given PKC isoform, and presents their
      isoform-selectivity. Furthermore, MPMA and 4alpha-PMA caused effects similar to
      those expected from PKC inhibition.

PMID- 15140627
TI  - Selective block of swelling-activated Cl- channels over cAMP-dependent Cl-
      channels in ventricular myocytes.
AB  - The objective of this study on guinea-pig and rabbit ventricular myocytes was to
      evaluate the sensitivities of swelling-activated Cl- current (ICl(swell)) and
      cAMP-dependent cystic fibrosis transmembrane regulator (CFTR) Cl- current
      (ICl(CFTR)) to block by dideoxyforskolin and verapamil. The currents were
      recorded from whole-cell configured myocytes that were dialysed with a Cs+-rich
      pipette solution and superfused with either isosmotic Na+-, K+-, Ca2+-free
      solution that contained 140 mM sucrose or hyposmotic sucrose-free solution.
      Forskolin-activated ICl(CFTR) was inhibited by reference blocker anthracene-9
      carboxylic acid but unaffected by < or = 200 microM dideoxyforskolin and
      verapamil. However, dideoxyforskolin and verapamil had strong inhibitory effects
      on outwardly-rectifying, inactivating, distilbene-sensitive ICl(swell); IC50
      values were approximately 30 microM, and blocks were voltage-independent and
      reversible. The results establish that dideoxyforskolin and verapamil can be used
      to distinguish between ICl(CFTR) and ICl(swell) in heart cells, and expand the
      pharmacological characterization of cardiac ICl(swell).

PMID- 15140628
TI  - The N-terminal of icatibant and bradykinin interact with the same Asp residues in
      the human B2 receptor.
AB  - The pharmacology of peptide and non-peptide bradykinin B2 receptor ligands was
      evaluated in the inositol phosphate (IP) production assay in CHO cells expressing
      the human bradykinin B2 receptor. The effect of single and double alanine
      mutation of D266 and D284 residues at the human bradykinin B2 receptor was
      evaluated on the agonist profile of bradykinin (H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
      Arg-OH) and the synthetic agonist FR190997 (8-[2,6-dichloro-3-[N
      methylcarbamoyl)cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2
      pyridylmethoxy)quinoline). Bradykinin potency (EC50 0.5 nM at the wild-type
      receptor) was reduced by 16-fold at D266A and D284A mutants and by 2300-fold at
      the D266A/D284A double mutant. None of the mutants affected the potency or the
      efficacy of FR190997. Peptide antagonists, Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi
      Ser-Dtic-Oic-Arg-OH) and MEN11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic
      Arg)c(7gamma-10alpha)) (100 nM) similarly antagonized the concentration-response
      curve to bradykinin or FR190997 (pA2 values 8.5 and 8.4 versus bradykinin and 8.2
      and 8.4 versus FR190997) at the wild-type receptor. Non-peptide antagonists
      FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8
      quinolinyl) oxymethyl]phenyl]-N-methylaminocarbonyl methyl]acrylamide) and LF16
      0687 (1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxy] methyl]
      phenyl]sulfonyl]-N-[3-[[4-(aminoiminomethyl)-phenyl]carbonylamino]propyl]-(S)
      pyrrolidine carboxamide) (100 nM) showed an equivalent potency values in blocking
      the IP production induced by bradykinin or FR190997 (pA2 values 8.7 and 8.8
      versus bradykinin and 8.8 and 8.6 versus FR190997). Whilst the antagonist potency
      of FR173657 and LF16-0687 was not affected by D266A/D284A double mutation (IP
      production induced by the synthetic agonist), that of Icatibant and MEN11270 was
      reduced by 50- and 200-fold. The antagonist potency of [Ala1]-Icatibant and
      [Ala2]-Icatibant (pA2 values at wild-type 7.7 and 6.4) was significantly less
      reduced (20-fold and 13-fold, respectively) by the D266A/D284A double mutation.
      Our results highlight a crucial role for two aspartic residues, D266 and D284,
      located at the top of transmembrane segments 6 and 7, in the high-affinity
      interaction of peptide antagonists with the human bradykinin B2 receptor. An
      interaction of these receptor residues with the N-terminal basic residues of
      Icatibant is hypothesized.

PMID- 15140629
TI  - Opioid receptor desensitization contributes to thermal hyperalgesia in infant
      rats.
AB  - Central nociceptive processing includes spinal and supraspinal neurons, but the
      supraspinal mechanisms mediating changes in pain threshold remain unclear. We
      investigated the role of forebrain neurons in capsaicin-induced hyperalgesia.
      Long-Evans rat pups at 21 days were randomized to undisturbed control group, or
      to receive tactile stimulation, saline injection (0.9% w/v) or capsaicin
      injection (0.01% w/v) applied to each paw at hourly intervals. Thermal paw
      withdrawal latency was measured 1 h later, forebrains were removed and purified
      forebrain neuronal membranes were assayed for adenylyl cyclase activity and
      opioid receptor function. Capsaicin-injected rats had decreased thermal latency
      (P < 0.0001) compared to the other groups. Neuronal membranes showed increased
      basal (P = 0.0003) and forskolin-stimulated (P=0.0002) adenylyl cyclase activity
      in the capsaicin group compared to other groups. The selective mu-opioid receptor
      agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) was less effective in
      inhibiting adenylyl cyclase activity in the capsaicin group (P < 0.001) compared
      to other groups. These effects were naloxone-reversible and pertussis toxin
      sensitive (P < 0.01) in the control, tactile stimulation and saline injection
      groups but not in the capsaicin group. Binding capacity and affinity for micro
      opioid receptors were similar in all four groups, suggesting that receptor
      downregulation was not involved. Exposure to DAMGO increased [35S]GTPgammaS
      binding to neuronal membranes from the control, tactile and saline groups
      (P<0.001) in a naloxone-reversible and pertussis toxin-sensitive manner (P <
      0.01) but not in the capsaicin group, suggesting mu-opioid receptor
      desensitization. Dose responses to systemic morphine were also reduced in the
      capsaicin group compared to the tactile group (P < 0.05). Capsaicin-induced
      hyperalgesia in 21-day-old rats was associated with an uncoupling of micro-opioid
      receptors in the forebrain. Opioid receptor desensitization in the forebrain may
      reduce opioidergic inputs to the descending inhibitory controls, associated with
      behavioral hyperalgesia and reduced responsiveness to morphine analgesia in
      capsaicin-injected young rats.

PMID- 15140630
TI  - Pharmacological characterization of the chronic constriction injury model of
      neuropathic pain.
AB  - The chronic constriction injury model is a rat model of neuropathic pain based on
      a unilateral loose ligation of the sciatic nerve. The aim of the present study
      was to test its sensitivity to various clinically validated and experimental
      drugs. Mechanical allodynia and thermal hyperalgesia developed within one week
      post-surgery and were reliably present for at least 7 weeks. Mechanical allodynia
      was strongly attenuated by morphine (minimal effective dose in brackets: 8 mg/kg,
      p.o.) and the cannabinoids Delta9-tetrahydrocannabinol (3 mg/kg, p.o.) and (-)
      cis-3-[2-hydroxy-4(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)
      cyclohexanol (CP 55,940; 0.05 mg/kg, i.p.), and weakly/moderately attenuated by
      the anticonvulsants gabapentin (50 mg/kg, i.p.) and carbamazepine (32 mg/kg,
      i.p.), the muscle relaxant baclofen (3 mg/kg, i.p.), and the adenosine kinase
      inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3
      d]pyrimidine (ABT-702; 30 mg/kg, i.p.). Thermal hyperalgesia was strongly
      attenuated by morphine (16 mg/kg, p.o.), Delta9-tetrahydrocannabinol (6 mg/kg,
      p.o.), CP 55,940 (0.025 mg/kg, i.p.), carbamazepine (32 mg/kg, i.p.) and the
      antidepressant amitriptyline (32 mg/kg, p.o.), and weakly/moderately attenuated
      by gabapentin (50 mg/kg, i.p.), the anti-inflammatory cyclooxygenase-2 inhibitor
      rofecoxib (30 mg/kg, i.p.) and the adenosine A1 receptor positive allosteric
      modulator 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophen-3-yl 4-chlorophenylmethanone
      (T62; 30 mg/kg, i.p.). Both symptoms were hardly or not affected by the
      nonselective N-methyl-d-aspartate receptor antagonists ketamine and dizocilpine,
      and the N-methyl-d-aspartate receptor NR2B-selective antagonists ifenprodil and R
      (R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenyl-methyl)-1-piperidine
      propranol (Ro 25-6981). The finding that mechanical allodynia and/or thermal
      hyperalgesia are attenuated by various established compounds further supports the
      validity of the chronic constriction injury model for the study of neuropathic
      pain and its use for the identification of novel treatments.

PMID- 15140631
TI  - 5-HT3 antagonist ICS 205-930 enhances naltrexone's effects on ethanol intake.
AB  - Opioid receptor antagonist naltrexone has shown some efficacy in decreasing
      ethanol consumption in humans. However, naltrexone treatment is not always
      efficacious and produces several aversive effects such as nausea, anxiety and
      weight loss. Serotonin-3 (5-HT3) receptor antagonists also modulate some of the
      behavioral effects of alcohol and may decrease alcohol consumption. We examined
      the effects of the combination of 5-HT3 receptor antagonist ICS 205-930 ((3
      tropanyl-indole-1-carboxylate, tropisetron) and naltrexone on ethanol and food
      intake in Sprague-Dawley rats. Both naltrexone (0.56-10 mg/kg) and ICS 205-930
      (5.6 mg/kg), when administered intraperitoneally 30 min before the scheduled 3-h
      access to ethanol, significantly suppressed ethanol intake. Naltrexone (1 mg/kg)
      when given in combination with ICS 205-930 (5.6 mg/kg) was significantly more
      efficacious in suppressing ethanol intake in comparison with naltrexone (1 mg/kg)
      administered alone. The drug combination did not affect the food intake. These
      data suggest that 5-HT3 receptor antagonist ICS 205-930 may be used as an
      effective adjunct for pharmacotherapy of alcoholism.

PMID- 15140632
TI  - Isradipine and dextromethorphan in methadone-maintained humans under a naloxone
      discrimination procedure.
AB  - In seven methadone-maintained human participants trained to distinguish between a
      low dose of naloxone (0.15 mg/70 kg, i.m.; i.e., Drug A) and placebo (i.e., Drug
      B) under an instructed novel-response drug discrimination procedure, the calcium
      channel blocker isradipine (0-10 mg/70 kg, p.o.; N=7) and the N-methyl-D-aspartic
      acid (NMDA) receptor antagonist dextromethorphan (0-60 mg/70 kg, p.o.; N=6) were
      tested each alone and in combination with the training dose of naloxone.
      Isradipine alone produced some naloxone- and novel-appropriate responding,
      minimal changes in self-reports and decreases in blood pressure. Dextromethorphan
      alone produced some novel-appropriate responding and minimal changes in self
      reports and vital signs. When combined with naloxone, isradipine significantly
      attenuated naloxone-occasioned responding, without increasing novel-appropriate
      responding, and attenuated naloxone-induced increases in opioid receptor
      antagonist ratings and ratings measuring sedation. Dextromethorphan significantly
      attenuated naloxone-appropriate responding, increased novel-appropriate
      responding, and enhanced naloxone's effects on ratings of dysphoric effects.
      These results suggest that isradipine attenuates and dextromethorphan enhances
      some of the behavioral effects of naloxone in opioid-dependent humans.

PMID- 15140633
TI  - Involvement of histaminergic system in the discriminative stimulus effects of
      morphine.
AB  - The interactions between morphine and the histaminergic system are not yet fully
      clarified. More especially, the involvement of the histaminergic system in the
      discriminative stimulus effects of morphine has not been determined. Therefore,
      the effects of histamine-related compounds on the discriminative stimulus effects
      of morphine were examined in rats. Combination tests using histamine-related
      compounds with morphine were initiated in rats trained to discriminate between
      3.0 mg/kg morphine and saline. Zolantidine (central histamine H2-receptor
      antagonist), but not pyrilamine (central histamine H1-receptor antagonist) or
      ranitidine (peripheral histamine H2-receptor antagonist), significantly
      attenuated the discriminative stimulus effects of morphine. The histamine
      precursor L-histidine significantly potentiated the discriminative stimulus
      effects of morphine. These results suggest that the discriminative stimulus
      effects of morphine are, at least in part, mediated through the central
      activation of histamine H2-receptors in rats.

PMID- 15140634
TI  - Hemodynamic characterization of left ventricular function in experimental
      coxsackieviral myocarditis: effects of carvedilol and metoprolol.
AB  - BACKGROUND: Carvedilol, a vasodilating nonselective beta-adrenoceptor antagonist,
      but not metoprolol, a selective beta1-adrenoceptor antagonist, has been shown to
      increase the production of cardiac antiinflammatory cytokines in experimental
      myocarditis. However, the hemodynamic consequences of these differences had not
      been investigated until today. Therefore, we determined the effects of carvedilol
      and metoprolol on left ventricular function in a murine model of coxsackievirus
      B3 (CVB3)-induced myocarditis. METHODS: BALB/c mice were inoculated with the
      coxsackie-B3 virus. Four and 10 days after infection, left ventricular function
      was investigated using a conductance micromanometer system. Additional groups
      were treated starting 24 h after infection using equipotent doses of carvedilol
      and metoprolol and studied on day 10. RESULTS: On day 4, infected mice manifested
      increased afterload-enhanced contractility and abnormal diastolic function. On
      day 10, contractile function of untreated mice was impaired. Carvedilol
      significantly improved cardiac index and most systolic indices, whereas
      metoprolol was substantially less effective. Diastolic dysfunction was not
      influenced by either of the beta-adrenoceptor antagonists. CONCLUSIONS: These
      hemodynamic data indicate that not only beta1-adrenoceptor blockade but also
      pleiotropic effects are involved in the cardioprotective effects of carvedilol on
      the pathophysiology of acute viral myocarditis.

PMID- 15140635
TI  - Cannabidiol lacks the vanilloid VR1-mediated vasorespiratory effects of capsaicin
      and anandamide in anaesthetised rats.
AB  - The results of vasorespiratory studies in rats anaesthetised with pentobarbital
      show that (+/-) cannabidiol, a cannabinoid that lacks psychotropic actions and is
      inactive at cannabinoid (CB) receptors, does not affect respiration or blood
      pressure when injected (1-2000 microg; 3.2-6360 nmol i.a.). Cannabidiol in doses
      up to 2 mg (6360 nmol) i.a. or i.v. did not affect the fall in mean blood
      pressure or the increase in ventilation (respiratory minute volume) caused by
      capsaicin and high doses of anandamide, responses that are mediated by activation
      of vanilloid VR1 (TRPV1) receptors in this species. Similar results were obtained
      with (-) cannabidiol (30-100 microg i.a.; 95-318 nmol). It has previously been
      shown using human embryonic kidney (HEK) cells over-expressing vanilloid human
      VR1 (hVR1) receptors that cannabidiol is a full agonist at vanilloid VR1
      receptors in vitro. However, in the intact rat cannabidiol lacked vanilloid VR1
      receptor agonist effects. We conclude that there are substantial functional
      differences between human and rat vanilloid VR1 receptors with respect to the
      actions of cannabidiol as an agonist at vanilloid VR1 receptors. Studies in vivo
      show that cannabidiol lacks any significant effect on mean blood pressure or
      respiratory minute volume when injected i.a. or i.v., and that this cannabinoid
      does not modulate the vanilloid VR1 receptor-mediated cardiovascular and
      ventilatory changes reflexly evoked by capsaicin or anandamide in rats
      anaesthetised with pentobarbital.

PMID- 15140636
TI  - Involvement of substance P in scratching behaviour in an atopic dermatitis model.
AB  - Substance P is speculated to be a key mediator of itching in atopic dermatitis,
      possibly acting via the tachykinin NK1 receptor. Thus, we examined the effect of
      a tachykinin NK1 antagonist, BIIF 1149 CL, on scratching behaviour in a
      picrylchloride-induced dermatitis model in NC/Nga mice. BIIF 1149 CL ((S)-N-[2
      [3,5-bis(trifluoromethyl) phenyl]ethyl]-4-(cyclopropylmethyl)-N-methyl-alpha
      phenyl-1-piperazineacetamide, monohydrochloride, monohydrate) at a dose of 100
      mg/kg, p.o., significantly inhibited scratching behaviour immediately after
      administration, and the effect continued up to 6 h. The results suggest that
      clinical trials of tachykinin NK1 antagonists for the treatment of itching in
      atopic dermatitis patients would be warranted.

PMID- 15140638
TI  - Drosophila model for in vivo pharmacological analgesia research.
AB  - Fruit flies (Drosophila melanogaster) are typically used for genetic studies but
      they also could be employed for neuropharmacological research. Therefore, we
      designed an apparatus and developed methods to investigate how injecting
      antinociceptive drugs, i.e., a gamma-aminobutyric acid B receptor agonist, to
      adult flies affects their avoidance of noxious heat stimuli. We found a drug
      induced dose-dependent increased threshold for heat avoidance and we propose
      Drosophila as an ethically acceptable animal model for in vivo pharmacological
      analgesia research.

PMID- 15140637
TI  - Antidiabetic and hypolipidemic potential of DRF 2519--a dual activator of PPAR
      alpha and PPAR-gamma.
AB  - We investigated the biological activity of Dr. Reddy's Research Foundation (DRF)
      2519, a benzoxazinone analogue of the thiazolidinedione class of compounds. In
      the in vitro transactivation assay, DRF 2519 showed interesting dual activation
      of Peroxisome Proliferator Activated Receptor (PPAR) alpha and gamma. In insulin
      resistant ob/ob mouse model, DRF 2519 showed significant alleviation of insulin
      resistance and dyslipidemia, which is better than rosiglitazone. Fatty Zucker
      rats treated with DRF 2519 showed better reduction of plasma insulin,
      triglyceride and free fatty acid levels than those treated with rosiglitazone. In
      addition, these rats were able to clear plasma lipids better when challenged with
      exogenous lipid (i.v.). DRF 2519 treatment resulted in improved plasma lipid
      profiles in high-fat-fed Sprague-Dawley rats. Treated rats showed better plasma
      lipid clearance and hepatic triglyceride secretion. When compared to DRF 2519,
      fenofibrate was comparatively less efficacious while rosigltiazone showed no
      activity in these models. In ex vivo studies, DRF 2519 showed induction of liver
      acyl CoA oxidase mRNA and increase in lipoprotein lipase (LPL) protein expression
      and activity in adipose tissue. In the in vitro studies, DRF 2519 inhibited the
      lipid biosynthesis and secretion of apolipoprotein B from human hepatoma (Hep)G2
      cells. It also enhanced insulin-induced relaxation of rat aortic smooth muscle.
      These results indicate that DRF 2519, a dual activator of PPAR-alpha and gamma,
      could be an interesting development candidate in the management of metabolic
      disorders and associated complications.

PMID- 15140639
TI  - Behavioral and histological effects of endoneurial administration of nerve growth
      factor: possible implications in neuropathic pain.
AB  - Animal models of neuropathic pain involving incomplete nerve injury result in
      causalgia-like symptoms, including thermal hyperalgesia and mechanical allodynia.
      Although current evidence links the overexpression of nerve growth factor (NGF)
      to peripheral neuropathic pain, the direct effect of NGF inside a nerve has not
      been evaluated yet. The purpose of this study was to investigate whether a
      single, low-dose (1-30 ng), endoneurial administration of NGF reproduces
      behavioral consequences of a partial nerve injury and to analyze the changes on
      myelinated fibers induced by NGF. Significant thermal hyperalgesia appeared on
      days 3 and 5 post-injection of NGF. NGF did not evoke mechanical allodynia at any
      of the assayed doses. On day 1, NGF induced focal degeneration and demyelination
      of fibers at the site of injection. Starting on day 5 clusters of small axons
      enclosed within one Schwann cell and associated with fibroblasts were observed,
      revealing axonal sprouting. Both thermal hyperalgesia and demyelination-sprouting
      processes induced by NGF were dose-dependent (1-30 ng) and the time course of
      both effects was similar. The injection of vehicle did not produce any behavioral
      or histological effect. These results suggest that overexpression of NGF may
      induce endoneurial sprouting and triggers the development of thermal
      hyperalgesia, but not mechanical allodynia, in peripheral neuropathic pain
      states.

PMID- 15140640
TI  - Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS.
AB  - The non-toxic neuronal binding domain of tetanus toxin (tetanus toxin fragment C,
      TTC) has been used as a vector to enhance delivery of potentially therapeutic
      proteins to motor neurons from the periphery following an intramuscular
      injection. The unique binding and transport properties of this 50-kDa polypeptide
      suggest that it might also enhance delivery of proteins to neurons after direct
      injection into the CNS. Using quantitative fluorimetry, we found that labeled TTC
      showed vastly superior retention within brain tissue after intracerebral
      injection compared to a control protein (bovine serum album). Fluorescence
      microscopy revealed that injected TTC was not retained solely in a restricted
      deposit along the needle track, but was distributed through gray matter in a
      pattern not previously described. The distribution of injected protein within the
      extracellular space of the gray matter and neuropil was also seen after injection
      of a recombinant fusion protein comprised of TTC linked to the enzyme superoxide
      dismutase (TTC-SOD-1). Injections of native SOD-1 in contrast showed only minimal
      retention of protein along the injection track. Immunohistochemistry demonstrated
      that both TTC and TTC-SOD-1 were distributed in a punctate perineuronal and
      intraneuronal pattern similar to that seen after their retrograde transport,
      suggesting localization primarily in synaptic boutons. This synaptic distribution
      was confirmed using HRP-labeled TTC with electron microscopy along with
      localization within neuronal endosomes. We conclude that TTC may be a useful
      vector to enhance neuronal delivery of potentially therapeutic enzymes or trophic
      factors following direct injection into the brain.

PMID- 15140641
TI  - From innervation density to tactile acuity: 1. Spatial representation.
AB  - We tested the hypothesis that the population receptive field representation (a
      superposition of the excitatory receptive field areas of cells responding to a
      tactile stimulus) provides spatial information sufficient to mediate one measure
      of static tactile acuity. In psychophysical tests, two-point discrimination
      thresholds on the hindlimbs of adult cats varied as a function of stimulus
      location and orientation, as they do in humans. A statistical model of the
      excitatory low threshold mechanoreceptive fields of spinocervical, postsynaptic
      dorsal column and spinothalamic tract neurons was used to simulate the population
      receptive field representations in this neural population of the one- and two
      point stimuli used in the psychophysical experiments. The simulated and observed
      thresholds were highly correlated. Simulated and observed thresholds' relations
      to physiological and anatomical variables such as stimulus location and
      orientation, receptive field size and shape, map scale, and innervation density
      were strikingly similar. Simulated and observed threshold variations with
      receptive field size and map scale obeyed simple relationships predicted by the
      signal detection model, and were statistically indistinguishable from each other.
      The population receptive field representation therefore contains information
      sufficient for this discrimination.

PMID- 15140642
TI  - Hypoxic/ischaemic cell damage in cultured human NT-2 neurons.
AB  - Postmitotic neurons were generated from the human NT-2 teratocarcinoma cell line
      in a novel rapid differentiation procedure. These neurons were used to establish
      an in vitro assay system that allows the investigation of hypoxic/ischaemic cell
      damage and the development of neuroprotective strategies. In experiments of
      simulated ischaemia, the neurons were subjected to anoxia and hypoglycaemia. The
      viability of NT-2 neuronal cells was significantly reduced by anoxia especially
      in the presence of glutamate, reflecting the cellular vulnerability to
      excitotoxic conditions. The addition of the N-methyl-D-aspartate (NMDA) receptor
      antagonist MK-801 reduced glutamate-induced neuronal damage. Calcium imaging
      showed that NT-2 neurons increased cytosolic calcium levels in response to
      stimulation with glutamate or NMDA, an effect that was abolished in calcium free
      medium and at low pH values. The NMDA receptor antagonists MK-801, AP 5 and
      ketamine reduced the NMDA-induced response, suggesting the presence of functional
      NMDA receptors in the human neuronal cells. The mitochondrial potential of
      neurons was estimated using the fluorescent dye rhodamine 123 (R123). The
      fluorescence imaging experiments indicated an energetic collapse of mitochondrial
      functions during anoxia, suggesting that the human NT-2 neurons can be used to
      investigate subcellular processes during the excitotoxic cascade.

PMID- 15140643
TI  - Preventing hyperthermia decreases brain damage following neonatal hypoxic
      ischemic seizures.
AB  - Neonatal seizures are the most common manifestation of underlying cerebral
      dysfunction. Hypoxic-ischemic encephalopathy is the cause of seizures in 40-60%
      of newborns. Previous work from our laboratory demonstrates that seizures
      associated with a hypoxic-ischemic insult results in aggravation of neuronal cell
      death, specifically within the hippocampus. The latter occurs in the setting of
      spontaneously occurring hyperthermia of 1.5 degrees C. The purpose of this study
      was to determine whether preventing the onset of seizure induced hyperthermia
      would be neuroprotective. Three groups of 10-day old rat pups received unilateral
      hypoxic-ischemic insults for 30 min followed by KA-induced seizures. Hyperthermia
      was prevented by lowering the environmental temperature ("relative hypothermia")
      to 29 degrees C such that the seizuring rat pups were normothermic. In one group,
      the prevention of hyperthermia occurred immediately following hypoxia-ischemia,
      whereas in the other group it occurred at the onset of seizures. The third group
      of rat pups (controls) remained at their nesting temperature and therefore became
      hyperthermic during seizures. Early (3 days) and late (20 days) neuropathology
      was assessed. Rat pups in whom hyperthermia was prevented during seizures
      displayed a significant reduction in brain damage compared to controls (p<0.05).
      Assessment of hippocampal brain damage also showed a significant improvement in
      neuronal necrosis at 20 days of recovery compared to 3 days of recovery (p<0.05).
      The results indicate that preventing spontaneous hyperthermia in this model of
      hypoxic-ischemic seizures in the newborn is neuroprotective.

PMID- 15140644
TI  - Olanzapine produces trophic effects in vitro and stimulates phosphorylation of
      Akt/PKB, ERK1/2, and the mitogen-activated protein kinase p38.
AB  - Olanzapine has previously been shown to stimulate the growth of neuronal cells in
      culture. A major goal of the present studies was to determine if olanzapine also
      provided neuroprotection to pheochromocytoma (PC12) cells, SH-SY5Y neuroblastoma
      cells, and primary cultures of rat cortical neurons. Olanzapine was mitogenic and
      enhanced the survival of PC12 cells, SH-SY5Y cells and 3T3 preadipocytes, but not
      L6 myoblasts or myeloma cells. It protected neuronal cells from death induced by
      serum and glutamine deprivation, amyloid beta peptide (25-35), and fluphenazine.
      Molecular mechanisms of the neuroprotection by olanzapine were explored,
      specifically the activation of various protein kinase signaling pathways
      including Akt/protein kinase B (PKB), extracellular-regulated kinase (ERK),
      ERK1/2, and mitogen-activated protein kinase (MAPK), p38. Olanzapine treatment
      led to rapid phosphorylation of kinases from all three pathways in PC12 cells.
      Phosphorylation of Akt was blocked with selective inhibitors (wortmannin and
      LY294002), which implicates phosphoinositide 3-kinase (PI3K) in the signaling
      cascade. Short-term mitogenic effects of olanzapine were abolished with a
      selective inhibitor of Akt, but not by inhibition of the ERK pathway. Other
      antipsychotic drugs stimulated phosphorylation of a subset of the kinase panel,
      but not all three kinases. The present findings demonstrate that olanzapine has
      both mitogenic and neuroprotective effects in neuronal cells.

PMID- 15140645
TI  - N1-dansyl-spermine: a potent polyamine antagonist.
AB  - The potential polyamine antagonist action of N1-dansyl-spermine (a potent NMDA
      antagonist) was assessed in two in vivo mouse models of polyamine action. Co
      administration of N1-dansyl-spermine (2-10 microg, i.c.v.) with spermine (100
      microg, i.c.v.) resulted in a dose-dependent antagonism of the spermine-induced
      CNS excitation (body tremor and fatal tonic convulsions). In addition, the same
      dose of N1-dansyl-spermine antagonised spermine's enhancement of NMDA-induced
      convulsions. These results suggest that N1-dansyl-spermine is in vivo a potent
      antagonist of the CNS effects of spermine and of its action at the positive
      polyamine modulatory site on the NMDA receptor.

PMID- 15140646
TI  - The neuroprotective effects of N1-dansyl-spermine in the gerbil model of cerebral
      ischaemia.
AB  - The effects of N1-dansyl-spermine, a polyamine antagonist, and ifenprodil, a non
      competitive N-methyl-D-aspartate (NMDA) receptor antagonist, were investigated in
      the gerbil model of global cerebral ischaemia. Transient forebrain ischaemia was
      induced by 5-min bilateral occlusion of the common carotid arteries. N1-dansyl
      spermine (2, 5 and 10 mg/kg) and ifenprodil (30 mg/kg) were administered
      intraperitoneally 30 min after bilateral carotid artery occlusion. On
      histological examination, 4 days (96 h) after ischaemia, there was a significant
      decrease in neuronal density of the hippocampal CA1 subfield. This reduction in
      neuronal density was attenuated in those animals treated with the 5 or 10 mg/kg
      dose of N1-dansyl-spermine and those treated with 30 mg/kg ifenprodil. However,
      unlike ifenprodil, N1-dansyl-spermine failed to attenuate the ischaemia-induced
      increase in locomotor activity. This demonstrates that polyamines play a
      significant role in the neuronal damage produced after cerebral ischaemia, while
      casting doubt on the suggestion that increased locomotor activity correlates with
      CA1 pyramidal cell damage.

PMID- 15140647
TI  - Role of NMDA receptor subtypes in the induction of catalepsy and increase in Fos
      protein expression after administration of haloperidol.
AB  - The increase of Fos expression in the striatum induced by haloperidol, an
      antagonist of the dopamine D2 receptor, might be related to the activation of
      glutamatergic neurotransmission, especially that of N-methyl-D-aspartate (NMDA)
      receptors. In this study, using behavioral and immunohistochemical techniques, we
      examined the effects of a noncompetitive NMDA antagonist, (+)-MK-801, and an NMDA
      receptor NR2B subunit antagonist, ifenprodil, on catalepsy, an extrapyramidal
      symptom; in this context, we also considered the expression of Fos protein in the
      forebrain after the administration of haloperidol. Catalepsy in mice, induced by
      the administration of haloperidol (1 mg/kg), was inhibited by pretreatment with
      (+)-MK-801 (0.2 mg/kg) or ifenprodil (10 mg/kg). Furthermore, pretreatment with
      (+)-MK-801 (0.2 mg/kg) significantly attenuated the induction of Fos
      immunoreactive (IR) cells in the dorsomedial, dorsolateral, and ventrolateral
      striatum, but not in the shell region of the nucleus accumbens after the
      administration of haloperidol, whereas pretreatment with ifenprodil (10 mg/kg)
      significantly attenuated the induction of Fos-IR cells in all of these areas. It
      is known that ifenprodil binds sigma receptors and alpha-1 adrenergic receptors
      with high affinity. Pretreatment with the sigma receptor antagonist BD-1407 (3
      mg/kg) or the alpha-1 adrenergic receptor antagonist prazosin (3 mg/kg) affected
      neither catalepsy nor the expression of Fos-IR cells after the administration of
      haloperidol. However, pretreatment with CP-101,606 (1 mg/kg), a selective
      antagonist for the NR2B subunit of the NMDA receptor, significantly attenuated
      catalepsy and the expression of Fos-IR cells in the forebrain after the
      administration of haloperidol. These results suggest that the NMDA receptor
      antagonists attenuated the induction of catalepsy and Fos-IR cells in forebrain
      after the administration of haloperidol. It was also suggested that haloperidol
      induced expression of Fos-IR cells in the shell region of the nucleus accumbens
      might be differentially regulated by NMDA receptor subunits. Therefore, it
      appears that selective antagonists for the NR2B subunit of the NMDA receptor
      (e.g., CP-101,606) might be useful drugs for the treatment of extrapyramidal side
      effects (EPS) associated with the chronic use of typical antipsychotics such as
      haloperidol.

PMID- 15140648
TI  - Chronic ethanol consumption transiently reduces adult neural progenitor cell
      proliferation.
AB  - Adult neural stem/progenitor cells proliferate throughout the life of the animal
      in the subependymal zone and the subgranular zone of the dentate gyrus (DG).
      Treatments such as enriched environment, dietary restriction, running and anti
      depressants increase proliferation, however, stress and opiates have been shown
      to decrease proliferation. While models of binge ethanol drinking decreases
      proliferation, few studies have characterized the effect chronic ethanol usage
      has on progenitor cell proliferation. In this study, we have examined changes in
      the progenitor cell proliferation rate following chronic ethanol consumption.
      Animals were given a nutritionally balanced liquid diet containing 6.5% v/v
      ethanol or an isocalorically balanced liquid diet. Bromodeoxyuridine (BrdU) was
      administered (150 mg/kg x 3) and the animals sacrificed 2 h after the last
      injection on days 3, 10 or 30 of the ethanol diet. Coronal brain blocks were
      paraffin embedded and 6 microm sections sliced and immunohistochemically stained
      for BrdU. Quantitation of the number of BrdU-labeled cells in the subgranular
      zone of the DG revealed a significant decrease only at the 3-day time-point, with
      recovery by the 10- and 30-day time-points. Thus, the progenitor cell
      proliferation rate is transiently decreased by chronic ethanol usage. This data
      suggests that chronic alcohol use results in a compensatory response that
      restores the progenitor cell proliferation rate.

PMID- 15140649
TI  - Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal
      retina and following optic nerve crush in adult rats.
AB  - Brain-derived neurotrophic factor (BDNF) is a well-known retinal neuroprotectant,
      but its effectiveness is limited: higher doses do not yield increased cell
      survival, multiple applications are not additive, and long-term delivery does not
      reverse, ganglion cell death. These limitations might reflect either injury- or
      BDNF-induced retinal changes in TrkB, the high affinity tyrosine kinase receptor
      used by BDNF. Retinal levels of TrkB protein and mRNA were measured in rats
      following intravitreal application of BDNF alone, optic nerve crush alone, and
      both. Full-length receptor protein levels (TrkB.FL) were determined by Western
      blot analysis and mRNA (trkB.FL) levels were measured using RNAse protection
      assay (RPA). BDNF alone produced a rapid and prolonged decrease in normal retina
      TrkB.FL. Nerve crush also resulted in decreased TrkB.FL, but the reduction was
      not apparent before 2-week post-crush. BDNF applied at the time of the crush
      yielded reductions in TrkB.FL similar to that of BDNF alone. With respect to TrkB
      mRNA levels, injection of BDNF into normal eyes and optic nerve crush alone
      showed bell-shaped patterns of change: approximately 50% below normal at 24-h
      post-procedure, approximately 50% above normal at 3 days, normal at 7 days, and
      approximately 50% below normal at 2-week post-procedure. When BDNF and nerve
      crush were combined, trkB-FL levels reached 90% of normal 1-week post
      crush/injection. The data suggest that the limitation of BDNF in promoting
      ganglion cell survival following optic nerve injury results, in part, due to drug
      induced down-regulation of the full-length TrkB receptor needed to activate
      intracellular pathways.

PMID- 15140650
TI  - Involvement of the mammillary bodies in spatial working memory revealed by
      cytochrome oxidase activity.
AB  - In view of the inconclusive findings relating the nuclei of the mammillary bodies
      (MB) with spatial memory, we evaluated the oxidative metabolic activity of the
      medial and lateral nuclei of the mammillary bodies (MB) after training young rats
      (30 days) of both sexes in the Morris water maze. Different groups were trained
      in spatial working (WM) or reference memory (RM) tasks, respectively. The
      corresponding naive groups swam for the same amount of time as the trained groups
      but without the escape platform. Control groups were added that had not been
      manipulated in any way. No sex-related differences were detected in the working
      memory task although males exhibited better reference memory than females.
      Cytochrome oxidase (CO) activity, an endogenous metabolic marker for neuronal
      activity, was measured in all the groups. CO activity increased significantly in
      both MB nuclei of male and female rats only in the spatial working memory group.
      In addition, high CO activity in the lateral nucleus of the MB was linearly
      correlated with lower escape latencies in both sexes after training in the
      working memory task. No CO activity changes were found in the basolateral
      amygdala (BL) in any of the experimental groups. This nucleus was used as a
      control brain region because of its participation in emotional behavior. The
      results suggest a specific role of the MB nuclei in spatial working memory in
      both sexes.

PMID- 15140651
TI  - The corticostriatal input to giant aspiny interneurons in the rat: a candidate
      pathway for synchronising the response to reward-related cues.
AB  - Tonically active neurons (TANs) in the mammalian striatum show a pause in their
      ongoing firing activity in response to an auditory cue that is paired with a
      reward. This response to reward-related cues develops through learning and
      becomes expressed synchronously by TANs located throughout the striatum. The
      pause response is abolished by inactivating the thalamic inputs to the striatum
      but a short-latency excitatory response to reward-related cues remains, which may
      originate in the cortex. We investigated the cortical inputs to striatal neurons
      to determine the electrophysiological properties of their cortical projections.
      We made in vivo intracellular recordings from 14 giant aspiny interneurons (which
      correspond to the TANs) and from a control group of spiny projection neurons
      (n=18) in urethane-anaesthetised rats. All giant aspiny interneurons were
      tonically active (firing rate: 3.0+/-1.5 Hz) and displayed small-amplitude
      subthreshold fluctuations in membrane potential. These fluctuations in membrane
      potential were correlated with the cortical electroencephalogram (EEG). Test
      stimulation of the contralateral cortex induced postsynaptic potentials (PSPs) in
      giant aspiny interneurons. These PSPs were significantly shorter in latency
      (5.1+/-1.6 ms) than those measured in spiny projection neurons (9.3+/-2.8 ms;
      p<0.01), whereas the latencies of ipsilaterally evoked PSPs did not differ. Taken
      together, these observations suggest that giant aspiny interneurons are under the
      significant influence of spontaneous excitatory inputs and receive specialised
      input from either faster conducting or less branching cortical fibres than spiny
      projection neurons. These inputs may be involved in the synchronised convergence
      of reward-related cues from spatially distinct cortical areas onto giant aspiny
      interneurons.

PMID- 15140652
TI  - Single footshock attenuates c-Fos expression induced by 5-HT2A receptor agonist
      (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in rat brain.
AB  - Administration of 3 mg/kg 5-hydroxytryptamine2A/2C (5-HT2A/2C) receptor agonist
      (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced c-Fos
      expression in all areas of the rat neocortex. The single footshock 24 h before
      DOI administration significantly attenuated DOI-induced c-Fos expression in layer
      IV of the primary somatosensory cortex. These changes in c-Fos expression suggest
      an adaptational change in the somatosensory cortex by acute stress.

PMID- 15140653
TI  - Vagus nerve stimulation inhibits harmaline-induced tremor.
AB  - Excessive olivo-cerebellar burst-firing occurs during harmaline-induced tremor.
      This system receives rich sensory inputs, including visceral. We hypothesized
      that electrical vagus nerve stimulation (VNS) would suppress harmaline tremor, as
      measured with digitized motion power in the rat. Cervical vagus nerve stimulation
      suppressed power in the 8-12-Hz tremor range by 40%, whereas sham stimulation was
      ineffective. This study raises the possibility that activation of various sensory
      modalities, as well as visceral, may reduce tremor.

PMID- 15140654
TI  - Surgical technology and its impact on practice.

PMID- 15140655
TI  - A rationale for therapy of skull-base tumours.

PMID- 15140656
TI  - Subspecialization and pancreaticoduodenectomy: learning experience from 71
      consecutive cases.
AB  - BACKGROUND: Pancreaticoduodenectomy (PD) is a major procedure with significant
      mortality and morbidity. In this study, we reviewed our departmental results with
      PD as subspecialization for hepatopancreaticobiliary surgery developed, and
      evaluated the effects on surgical technique and practice. METHODS: Between
      January 1995 and October 2000, 71 consecutive patients underwent PD for various
      diseases at our institution. Patients were analysed in two groups according to
      the 35-month time period in which they underwent surgery: Group A, January 1995
      to November 1997 (n = 28), and Group B, December 1997 to October 2000 (n = 43).
      RESULTS: The two groups were comparable for age, gender distribution, race and
      associated medical illnesses. Overall 30-day mortality was 5.6% (n = 4); three
      patients (10.7%) died in Group A and one (2.3%) in Group B. Compared to Group A,
      there was less surgery-related morbidity (25% vs 16.3%), intraoperative median
      blood loss (700 mL vs 500 mL), and median intensive-care stay (2 days vs 1 day)
      in Group B. No significant changes were noted in the overall complication rates
      (35.7% vs 39.5%), median operating time (4.7 vs 6.1 hours), median blood
      transfusion requirement (1.46 vs 1.29 units), and median hospital stay (17 vs 18
      days). There was a significant shift away from pancreaticojejunostomy (PJ)
      reconstruction towards pancreaticogastrostomy (PG), especially in Group B.
      Although preoperative histological confirmation of carcinoma was important in the
      earlier group, there was less emphasis on this need for a diagnosis before
      resection in the later period. CONCLUSIONS: Subspecialization in our department
      has improved the results of PD to an acceptable level, with a mortality of only
      2.3%. However, this procedure still causes morbidity, with surgery-related
      morbidity of 16.3% even with subspecialization. Whether further reductions in
      morbidity can be achieved with more technical innovations remains to be seen. PG
      reconstruction was safer than PJ in our practice, with no anastomotic leaks.

PMID- 15140657
TI  - T-tube jejunostomy feeding after pancreatic surgery: a safe adjunct.
AB  - OBJECTIVE: Patients with pancreatic disease are often malnourished because of
      biliary and gastric outlet obstruction or the catabolic response to sepsis or
      cancer. In this study, we reviewed our experience of providing enteral nutrition
      through a T-tube jejunostomy in these patients. METHODS: The records of a
      consecutive series of 36 patients who had undergone pancreatic operations during
      the last 4 years were reviewed. Data were collected on preoperative nutritional
      status and postoperative feeding. RESULTS: All patients had partially hydrolysed
      feeds administered through a T-tube jejunostomy, placed during pylorus-preserving
      proximal pancreatoduodenectomy (21 patients), Whipple's procedure (4),
      debridement of pancreatic necrosis (3), palliative bypass (2), distal
      pancreatectomy (2), cyst-jejunostomy (3) or accessory sphincteroplasty (1). Tube
      feeding was employed for a mean of 18 days. There were no related deaths. Eight
      patients had complications directly attributable to the tube, including blockage
      (4), dislodgement (2), pericatheter leakage (2) and peritonitis (1). Twenty
      patients had complications related to feeds that included transient diarrhoea
      (13), abdominal distension (8), nausea or vomiting (6) and pain (6).
      Consequently, nitrogen and energy needs were completely fulfilled in only 19
      patients. CONCLUSION: Despite many minor shortcomings, jejunostomy tube feeding
      appears to be a safe adjunct to pancreatic surgery.

PMID- 15140658
TI  - Functional analysis of chromosome 18 in pancreatic cancer: strong evidence for
      new tumour suppressor genes.
AB  - BACKGROUND: In a previous work, we demonstrated that loss of heterozygosity of
      18q is a frequent event significantly associated with poor prognosis in
      pancreatic cancer. We hypothesized that restoration of heterozygosity of
      chromosome 18 in pancreatic cancer cells would reduce their tumorigenicity. This
      study was intended to provide functional evidence for the existence of new tumour
      suppressor gene(s) located on chromosome 18. METHOD: Restoration of
      heterozygosity was achieved by introducing a normal copy of chromosome 18 into
      pancreatic ductal carcinoma using a microcell-mediated chromosome transfer
      technique. The tumorigenicity and metastatic ability of both the parental cells
      and resulting hybrids were assessed in vitro and in vivo. RESULTS: In vitro
      growth of hybrid clones was significantly delayed compared to parental cells.
      This was paralleled by a significantly lower rate of promoting invasive carcinoma
      in nude mice and a longer latency with hybrid cells compared with parental tumour
      cells. Hybrid clones showed significant suppression in the number of surface lung
      metastases when compared with parental cells. CONCLUSION: These data represent
      strong functional evidence that chromosome 18q encodes strong tumour and
      metastasis suppressor activity that is able to switch human pancreatic cancer
      cells to a dormant phenotype.

PMID- 15140659
TI  - Effect of inducible cyclooxygenase expression on local microvessel blood flow in
      acute interstitial pancreatitis.
AB  - OBJECTIVE: To investigate the role of inducible cyclooxygenase (COX-2) mRNA
      expression in local microvessels in rats with acute interstitial pancreatitis
      (AIP) induced by caerulein injection. METHODS: The reverse transcription
      polymerase chain reaction (RT-PCR) was used to detect COX-2 gene expression in
      pancreatic tissue. Parameters of acute pancreatitis, such as serum amylase (AMS)
      and plasma myeloperoxidase (MPO) activities, were assayed using
      spectrophotometry. Intravital fluorescence microscopy with fluorescein
      isothiocyanate-labelled erythrocytes was used to study the pancreatic
      microvessels of rats with AIP and normal control rats. RESULTS: Highly
      significant increases in COX-2 expression and AMS and MPO activity were seen in
      rats with AIP compared with controls. After caerulein injection, pancreatic
      capillary blood flow was decreased (4 hours, p > 0.05; 8 hours, p < 0.001),
      functional capillary density was reduced (4 hours, p > 0.05; 8 hours, p < 0.001),
      and there was irregular and intermittent capillary perfusion at 8 hours. There
      was also a positive correlation between the level of COX-2 expression and MPO
      activity (plasma, r = 0.5449, p < 0.05; tissue, r = 0.5698, p < 0.05).
      CONCLUSIONS: The correlations between increased COX-2 expression and decreased
      capillary perfusion and blood flow and increased oedema following AIP may show
      that COX-2 expression can induce neutrophil sequestration to the pancreas, which
      may be one of the cascading inflammatory factors in the development of AIP.

PMID- 15140660
TI  - Magnetic resonance cholangiography: applications in patients with calculus
      disease of the biliary tract.
AB  - Magnetic resonance cholangiography (MRC) is a non-invasive imaging modality that
      has become widely available. In the short time since its introduction, MRC has
      been shown to possess excellent accuracy for the diagnosis of various biliary
      pathologies, including choledocholithiasis. Investigations of the clinical
      applications of MRC are ongoing. This review summarizes the diagnostic
      capabilities of MRC and discusses its application in the management of patients
      with gallstone diseases.

PMID- 15140661
TI  - Clinical analysis of pericardial devascularization by preserving vagus trunks in
      42 patients with portal hypertension.
AB  - Pericardial devascularization (PD) is less of a burden and provides better
      bleeding control to patients compared to shunt procedures, and so has been widely
      used in portal hypertension in China. However, because the vagus trunks are
      interrupted during surgery, patients easily suffer from postoperative stomach
      adynamia. Based on our understanding from autopsy of the path of vagus trunks
      along the distal oesophagus, we designed the operative procedure of PD by
      preserving vagus trunks (PDPVT) to treat portal hypertension. Between May 1991
      and January 2003, patients with portal hypertension were treated surgically using
      PDPVT (n = 42), single PD (n = 32), or PD with pyloroplasty (PD+PP; n = 16).
      Operative mortality was 2.4% in the PDPVT group and 6.3% in both the PD and PD+PP
      groups (p > 0.05). The postoperative rebleeding rate was 9.5% in the PDPVT group
      and 12.5% in both the PD and PD+PP groups (p > 0.05). There were no differences
      in operative time and estimated blood loss between the three groups (p > 0.05).
      The recovery time for gastroenteric function was shorter with PDPVT (mean, 3.5
      days) than with PD (mean, 5.7 days) and PD+PP (mean, 4.2 days; p < 0.02).
      Incidences of early satiety and enterogastric reflux were significantly lower in
      the PDPVT group (both 4.8%) than in the PD group (46.9% and 18.8%) and PD+PP
      group (12.5% and 100%; p < 0.005). Incidences of retention of gastric juice,
      diarrhoea and late gallstones were 12.5%, 15.6% and 7.1%, respectively, in the PD
      group, and 12.5%, 18.8% and 6.3%, respectively, in the PD+PP group, but none of
      these were observed in the PDPVT group. Since it preserves vagus trunks, PDPVT
      can maintain normal stomach dynamics and physiological function of hepatobiliary
      and gut systems better than PD and PD+PP, thus reducing incidences of
      postoperative complications. Thus, PDPVT is superior to PD and PD+PP in the
      treatment of portal hypertension.

PMID- 15140662
TI  - Use of elderly donors (> 60 years) for liver transplantation.
AB  - BACKGROUND: As the demand for liver transplantation has become greater than the
      availability of donor livers, the criteria for donor selection or rejection are
      more important than ever before. In view of an increasing number of patients on
      the waiting list, some centres are expanding their donor pool by relaxing the
      criteria, such as by using organs from elderly (> 60 years) brainstem-dead
      donors. In this study, we reviewed our experience of using elderly brain-dead
      donor livers, investigating the potential prognostic factors of the donor, and
      analysing the influence of donor age on early graft function and graft survival.
      METHODS: We retrospectively evaluated 106 cadaveric donor liver transplantations
      in 98 patients. Seven patients (6.6%, 7 vs 106) received livers from donors older
      than 60 years. Pre-transplantation characteristics of donors and the outcome of
      recipients were evaluated. Donor prognostic factors were analysed using Cox
      univariate analysis and confirmed by a multivariate forward stepwise Cox model.
      Early graft function was compared between recipients of grafts from donors older
      and younger than 60 years. RESULTS: There were no primary non-functions or re
      transplants in the group receiving elderly grafts. Early graft function was
      similar in patients with grafts from elderly and younger donors. Univariate
      analysis demonstrated that prognostic factors had no relationship with long-term
      recipient survival. The 3-month and 1-year cumulative graft survival rates were
      100% and 82% in the elderly graft group and 84% and 83% in the younger graft
      group, respectively. Kaplan-Meier curves and the log-rank test indicated that
      there was no difference in graft and patient survival rates between the two
      groups. CONCLUSIONS: Old age is not a contraindication for liver donation. Liver
      grafts from donors older than 60 years can be used safely.

PMID- 15140663
TI  - Bowel preparation for colonoscopy: a randomized controlled trial comparing
      polyethylene glycol solution, one dose and two doses of oral sodium phosphate
      solution.
AB  - OBJECTIVES: To compare three bowel preparation regimens for colonoscopy in terms
      of the quality of preparation, the side effects and patient acceptance. METHODS:
      A total of 299 patients who underwent colonoscopy were randomized to three bowel
      preparation regimens: polyethylene glycol solution (n = 106), or a single dose (n
      = 92) or two doses (n = 101) of sodium phosphate solution. The colonoscopists who
      recorded the quality of bowel preparation were blind to the preparation regimens.
      The discomforts associated with bowel preparation and patient acceptance of the
      preparation were also recorded. RESULTS: Two doses of sodium phosphate solution
      achieved significantly better bowel preparation than polyethylene solution or a
      single dose of sodium phosphate solution (p < 0.05). Although two doses of sodium
      phosphate solution was associated with more dizziness and anal irritation,
      patients preferred preparation with sodium phosphate solution than with
      polyethylene glycol solution. Of the 69 patients in the sodium phosphate solution
      groups who had prior experience of bowel preparation using polyethylene glycol
      solution, 55 patients (80%) stated that they preferred sodium phosphate solution.
      CONCLUSION: Two doses of sodium phosphate solution achieved better bowel
      preparation than polyethylene glycol solution and was more acceptable to
      patients. A single dose of sodium phosphate did not achieve similar bowel
      preparation to two doses of the solution.

PMID- 15140664
TI  - Crucial role of rectoanal inhibitory reflex in emptying function after anoplasty
      in infants with anorectal malformations.
AB  - Constipation is a common problem after reconstructive surgery for anorectal
      malformations. The underlying pathophysiology of the constipation in these
      patients is unclear. The objective of this study was to compare manometric
      disturbance in infants with and without post-anoplasty constipation. Anorectal
      manometry studies were performed within 12 months of anoplasty, as a part of the
      follow-up protocol, in 24 infants aged less than 3 years who had anorectal
      malformations. The manometric profiles studied were mean resting anal pressure
      (ArP), mean resting rectal pressure (RrP), mean resting rectoanal pressure
      gradient (RRPG), peak squeeze pressure (PSP), and the presence of the rectoanal
      inhibitory reflex (RAIR). Eight of 24 infants (33%) experienced constipation
      during the examination period. There was no difference in pressure profiles
      between low and non-low anomalies. In the non-constipation group, RrP was 5.1
      mmHg, ArP was 21.0 mmHg, RRPG was 16.0 mmHg, and PSP was 88.4 mmHg. In the
      constipation group, RrP was 7.3 mmHg (p = 0.37), ArP was 37.5 mmHg (p = 0.03),
      RRPG was 3.05 mmHg (p = 0.05), and PSP was 81.7 mmHg (p = 0.77). RAIR was present
      in 93.75% of cases without constipation and 12.5% of cases with constipation (p <
      0.01). One patient who had clinical conversion from constipation to a good result
      also showed positive conversion of the RAIR. RAIR and anal resting tone play
      important roles in emptying function. As far as possible, these functions should
      be preserved during reconstruction.

PMID- 15140665
TI  - Overview of breast cancer in Malaysian women: a problem with late diagnosis.
AB  - Breast cancer is the most common cancer among Malaysian women. There is a marked
      geographical difference in the worldwide incidence of breast cancer, with a
      higher incidence in developed countries compared to developing countries. From
      1998 to 2001, new cases of breast cancer presenting to the breast clinics at
      Hospital Kuala Lumpur and University Malaya Medical Centre, Malaysia, were
      reviewed; the race, age and stage at presentation were analysed. Of 774 cases
      seen in Hospital Kuala Lumpur, only 5.2% (40/774) were impalpable breast cancers
      diagnosed on mammography. The prevalent age group was 40 to 49 years, and the
      median age was 50 years. The average size of the tumour was 5.4 cm in diameter.
      Malay women appear to have larger tumours and a later stage at presentation than
      other ethnic groups; 50% to 60% were in late stages (Stages 3 and 4). During the
      same period, 752 new cases of breast cancer were seen in the University Malaya
      Medical Centre. The average tumour size was 4.2 cm, and 30% to 40% were in late
      stages. The age incidence was similar. The delay in presentation of breast cancer
      was attributed to a strong belief in traditional medicine, the negative
      perception of the disease, poverty and poor education, coupled with fear and
      denial. A prospective, population-based study is required to determine the
      demographic pattern of breast cancer and the factors delaying presentation. These
      findings will have important implications in future programmes to promote the
      early detection of breast cancer, as well as in understanding geographical as
      well as racial variations in the incidence of breast cancer.

PMID- 15140666
TI  - Follow-up of long-term treatment with clean intermittent catheterization for
      neurogenic bladder in children.
AB  - OBJECTIVES: To assess the results of long-term clean intermittent catheterization
      (CIC) treatment for neurogenic bladder in children born with myelomeningocele,
      and to compare the long-term results between the early treatment group (< 1 year
      old) and late treatment group (> 3 years old). METHODS: Thirty-six paediatric
      patients with myelomeningocele who were treated in the first year of life (Group
      1) and 31 cases who were treated after the age of 3 years (Group 2) were followed
      regularly for at least 11 years. All medical records were reviewed and long-term
      results of treatment, including increases in blood urea nitrogen (BUN) and serum
      creatinine, development of hydronephrosis, recurrent upper urinary tract
      infection, and the number of augmentation cystoplasties needed, were noted.
      Kaplan-Meier methods were used to analyse time-to-event data. RESULTS: Mean age
      at start of treatment was 6.88 months (range, 3-1 months) in Group 1 and 44.97
      months (range, 37-60 months) in Group 2. Increases in BUN and serum creatinine
      were found in 12 cases (33.3%) in Group 1 and 19 cases (61.3%) in Group 2.
      Patients in Group 2 showed earlier renal deterioration and worse renal function
      at the last follow-up. Hydronephrosis was found in 10 cases (27.8%) in Group 1
      and 18 cases (58.1%) in Group 2. Patients in Group 2 also had earlier and more
      severe hydronephrosis. Augmentation cystoplasty was needed in five cases (13.9%)
      in Group 1 and 10 cases (32.3%) in Group 2. The results of surgery were better in
      Group 1 than in Group 2, and surgery was needed earlier in Group 2 compared with
      Group 1. There was no significant difference regarding upper urinary tract
      infection between the two groups. CONCLUSIONS: For most patients and with close
      long-term follow-up, early treatment of neurogenic bladder using CIC in children
      born with myelomeningocele yields better results than late treatment. In our
      experience, treatment is recommended as soon as possible, especially during the
      first year of life.

PMID- 15140667
TI  - Haemorrhage from pancreatic pseudocysts presenting as upper gastrointestinal
      haemorrhage.
AB  - Haemorrhage is a rare but frequently fatal complication of pancreatic
      pseudocysts. The high mortality associated with pancreatic haemorrhage makes
      prompt and aggressive management essential. Occasionally, haemorrhage may present
      atypically, leading to delay in its diagnosis and management. This report details
      a case of pancreatic haemorrhage presenting as an upper gastrointestinal bleed
      and discusses the subsequent management. When managing patients with pancreatic
      pseudocysts who present with the stigmata of upper gastrointestinal bleeding, the
      possibility that the bleeding originates from the pancreas must always be borne
      in mind.

PMID- 15140668
TI  - ENT management of a child with CHARGE association.
AB  - The acronym CHARGE is used to describe specific congenital birth defects in
      children: colobomata, heart defect, atresia of the choanae, retarded growth or
      development, genital hypoplasia, and ear anomalies or deafness. CHARGE
      association with hearing impairment is a challenge to ENT surgeons. We report the
      case of a child with CHARGE association who underwent cochlear implantation using
      an unconventional surgical approach and review the postoperative speech
      perception results. The benefits of cochlear implantation in children with
      multiple congenital defects are discussed.

PMID- 15140669
TI  - Unusual retrorectal lesion.
AB  - Retrorectal lesions are rare entities. We report the complete clinicopathological
      details of an unusual retrorectal lesion composed of low-grade endometrioid
      adenocarcinoma and propose that this is a malignant change in pluripotent cells
      arising within a long-standing retrorectal tailgut lesion. To the best of our
      knowledge, this is the first case report of this malignancy in a retrorectal
      tailgut cyst.

PMID- 15140670
TI  - How safe is adjuvant chemotherapy and radiotherapy for rectal cancer?
AB  - Over the last three decades, a series of clinical trials have led to the use of
      adjuvant pelvic radiotherapy and chemotherapy in high-risk (T3-4 or N1) rectal
      cancer. There is a need to improve patient selection in order to identify the
      group most at risk for recurrent disease. The toxicity of adjuvant therapy should
      be factored into this consideration. The optimal sequencing of adjuvant therapy
      before or after surgery, the use of short- or long-course radiotherapy, and the
      utility of concurrent chemotherapy is currently being examined in randomized
      controlled trials (RCTs). The aim of this report was to review the morbidity and
      mortality in all RCTs of adjuvant therapy for rectal cancer.

PMID- 15140671
TI  - Professor Tan Sri Guan Bee Ong, P.S.M., O.B.E., M.D., D.Sc.

PMID- 15140672
TI  - Age difference on a coincident anticipation task: influence of stereotypic or
      "preferred" movement speed.
AB  - Two experiments were performed as an initial attempt to explain age related
      limitations in response accuracy on a coincident anticipation task. Five- to 9
      year-old boys and adult males participated in each experiment. They made
      horizontal arm movements in response to stimuli from a Bassin Anticipation Timer.
      The results of Experiment l confirmed the findings of previous studies, which
      showed that young children respond early to slow moving stimuli. They were most
      accurate at intermediate speeds; their responses deteriorated as speed was
      increased. older children and adults were more accurate at slow to intermediate
      speeds; their performances also declined at fast stimulus velocities. Experiment
      ll examined use of a stereotypic or default movement speed as an explanation for
      these results, particularly for young children. A most comfortable movement pace
      was determined for each subject and was used as a baseline speed for a subsequent
      timing task. Four other stimuli were selected in 0.8 mph increments from the
      baseline speed (two faster, two slower). In addition, selected trials for 6
      subjects at each age were filmed at 32 fps. X-coordinates for these trials were
      obtained and smoothed at 5 Hz. Movement time data suggested that 5-year-olds used
      a preferred or stereotypic speed, since they were accurate only when responding
      to their baseline speed. older subjects matched stimuli up to and including their
      baselines. Kinematic characteristics confirmed the general notion of preferred
      speed for 5-year-olds. These same measures demonstrated that older subjects were
      increasingly adaptable in their responses, despite a failure to respond more
      accurately. Consequently, the term "preferred speed" lacks generality as an
      explanatory concept. Age-related shifts in the ability to modify components of a
      response, like average movement velocity and number of corrections, were used to
      explain accuracy differences.

PMID- 15140673
TI  - Speed-accuracy characteristics of saccadic eye movements.
AB  - Speed-accuracy trade-off characteristic of horizontal saccadic eye movements were
      examined in this study. Unlike limb movements, saccadic eye movements are
      preprogrammed, unidimensional, and do not involve target impact. Hence, they
      provide an optimal test of the impulse variability account of the speed-accuracy
      trade-off in rapid movements. Subjects were required to alternately look at two
      target lights as fast and as accurately as possible for a period of 10 s. Target
      lights subtended angles of 5, 10, 15, and 20 degrees. By restricting target
      distances to less than 20 degrees of arc, the speed-accuracy relation was
      examined for single horizontal saccadic movements of the eye. movement of the
      dominant eye was tracked with an infra-red eye monitoring device. Fifty saccadic
      movements of the eye were recorded for each target distance and used to compute
      the average amplitude, duration, and velocity of eye movements, as well as,
      movement endpoint variability. An increase in both average velocity and movement
      endpoint variability with increasing movement amplitude was found. This, together
      with the unique features of the eye movement system, support the impulse
      variability account of the speed-accuracy trade-off in rapid movements.

PMID- 15140674
TI  - Relation between EMG activation patterns and kinematic properties of aimed arm
      movements.
AB  - Aimed flexion movements of the arm of different amplitude and duration were
      studied. Velocity and acceleration traces of movements with equal duration but
      different amplitude were equal, apart from a scaling factor (ratio between
      movement amplitudes). After appropriate scaling, EMG activity of the first
      agonist burst for these movements superimposed. This was not true for EMG
      activity in the antagonist muscle. For movements with equal amplitude, but
      different duration, the time to peak acceleration was constant for all MT'.
      Except for this fact, traces of acceleration, velocity, and agonist activity
      following the time of peak acceleration were about equal after appropriate
      scaling in time and amplitude. The integral of EMG activity in the first agonist
      burst increased linearly with peak velocity. For the antagonist burst, the
      integrated EMG activity increased more than proportionally. During movements made
      as fast as possible, subjects used a different strategy by varying the duration
      of the accelerating phase for movements of different amplitude. Movement
      amplitude was achieved by adjusting the duration of the agonist burst and the
      onset time for the antagonist muscle. Amplitude of the antagonist burst was
      constant within a narrow range for movements of different amplitude. These
      results did not change when the inertial mass was doubled by loading the arm with
      an additional mass.

PMID- 15140675
TI  - Some characteristics of EMG patterns during locomotion: implications for the
      locomotor control process.
AB  - Myoelectric signals from several muscles of the lower limb were studied under
      various speed and stride length conditions. The main purpose was to determine
      invariant and variant features among these myoelectric patterns. A pattern
      recognition algorithm was used to analyze these activity patterns. Within
      condition analysis revealed some common features among the EMG patterns. This
      suggests that the nervous system does not have to generate all the muscle
      activity patterns, only the common features that can, in appropriate combination,
      produce the necessary activity patterns. From the across condition analysis, the
      following rules emerged. First, both phasic component and magnitude (d.c. level)
      of the muscle activity patterns have to be modulated to meet the demands imposed
      by the various conditions. Second, the variability in the proximal muscle
      activity patterns across conditions are higher than the distal muscle activity
      patterns. Within each group, the extensor muscles and double-jointed muscles show
      greater variability than the flexor muscles and single-jointed muscles. And
      finally, the changes in the average value (d.c. level) of the muscle activity
      patterns across conditions are not uniform but show muscle and task specificity.
      For example, within the speed condition, the increase in d.c. level of the
      extensors with speed of locomotion show a proximal to distal trend. Based on
      these results, a conceptual model for the human locomotor control process is
      proposed.

PMID- 15140676
TI  - Analysis of vertical displacements of the center of gravity in the cat during
      limb flexion induced by cortical stimulation.
AB  - A limb movement and the associated postural adjustment result in a displacement
      of the center of gravity of the body. The vertical component of this displacement
      has been calculated from the variations in the sum of vertical forces at each
      limb. Through these variations, it is possible to measure the vertical
      acceleration of the center of gravity. Velocity and displacement are then
      obtained by two successive integrations of acceleration values. The magnitude of
      displacement of the center of gravity depends on the magnitude of limb
      displacement, and hindlimb flexion induces larger displacement than forelimb
      flexion. It is also directly linked to the time course of the vertical force
      variations recorded at each limb. The feed-forward character of the postural
      adjustment appears to minimize this amplitude, which leads us to discuss the
      functional significance of this postural adjustment.

PMID- 15140677
TI  - A note on accepting the null hypothesis: problems with respect to the mass-spring
      and pulse-step models of movement control.
AB  - Models are sometimes developed on the premise that there are no differences
      between two or more conditions regardless of experimental manipulation. This
      article argues that unless a very sensitive experiment (or series of experiments)
      was conducted, such conclusions are often premature. Design and statistical
      factors such as alpha level, variability, sample size, and treatment effect are
      all determinants of the sensitivity of the experiment. It is sometimes the case
      that an experiment produces differences between means and yet the null hypothesis
      is not rejected because of high variability within experimental conditions or
      because too few subjects were used. Unless the probability of detecting a
      difference between groups is known, it would seem unwise to conclude that no
      difference exists. Judgment on the model should be suspended. Examples are taken
      from the mass-spring and pulse-step models fro voluntary movement control to
      illustrate the problem.

PMID- 15140678
TI  - Science and statistics in motor physiology.

PMID- 15140679
TI  - The role of similarity analysis in understanding movement.

PMID- 15140680
TI  - Is "the mass-spring model" a testable hypothesis?

PMID- 15140681
TI  - Some aspects of the motor organization of the oculomotor system.
AB  - Oculomotor responses in looking to visual targets were examined for motor
      coordination parallel to that found in manual pointing. ocular responses did not
      show any evidence that speed-accuracy tradeoff when the correlation of latency
      (reaction time) and accuracy was assessed. The oculomotor system did show a range
      effect, hidden under a general undershoot of target position and present only
      when no visual feedback about target position was available to allow correction
      during the movement. Cues to allow predictive timing of the response seemed very
      important for oculomotor reaction time. processing of timing of movement may be
      handled differently for oculomotor than for manual orienting, and calculation of
      position in space may be processed in common, leading to both similarities and
      differences for the two motor systems.

PMID- 15140682
TI  - Role of timing of visual monitoring and motor rehearsal in observational learning
      of action patterns.
AB  - This experiment tested the hypothesis that observational learning is enhanced by
      visual monitoring of enactments that is optimally timed for conception-action
      matching and by motor rehearsal that serves to refine the cognitive
      representation. Subjects observed a modeled action pattern, after which they
      enacted it with either concurrent, delayed, or no visual monitoring. They then
      engaged in motor rehearsal or did not rehearse the action pattern. Development of
      the cognitive representation of the modeled action was also measured. Concurrent
      visual monitoring of enactments greatly facilitated observational learning,
      whereas delayed visual monitoring did not affect the acquisition process.
      Rehearsal aided cognitive representation and behavioral reproduction. The more
      accurate the cognitive representation of the modeled action pattern, the more
      skilled were the subsequent reproductions of it. After gaining proficiency in
      converting conception to action, subjects showed no decline in reproduction
      accuracy when modeling and visual monitoring were withdrawn.

PMID- 15140683
TI  - Influence of practice schedule on testing schema theory predictions in adults.
AB  - Since the publication of Schmidt's (1975) schema theory of motor learning,
      numerous studies have assessed the variability of practice hypothesis. Of these,
      only research using children as subjects has provided consistent results.
      Findings from adult studies have been equivocal. Two experiments were conducted
      to assess the possibility that the schedule of variable practice during
      acquisition may be a clue to this equivocality, since only experiments (using
      adults as subjects) that have provide random variability of practice conditions
      have consistently supported the tenets of schema theory. Using a two movement
      rapid timing task, subjects learned to control their actions under one (constant)
      or four (variable) parameters, with variable practice conducted under either a
      blocked or a randomized schedule. Results for variable error and absolute
      constant error showed that random-variable practice provided strong support for
      the schema theory prediction, whereas blocked-variable practice provided only
      relatively weak support. Two contrasting implications of these results are
      discussed with respect to support versus non-support for Schmidt' schema theory.

PMID- 15140684
TI  - Response timing variability: coherence of kinematic and EMG parameters.
AB  - A detailed kinematic and electromyographic (EMG) analysis of single degree of
      freedom timing responses is reported to (a) determine the coherence of kinematic
      and EMG variability to the reduced timing error variability exhibited with
      amplitude increments within a given criterion movement time and (b) understand
      the temporal organization of various movement parameters in simple responses. The
      data reveal that the variability of kinematic (time to peak acceleration,
      duration of acceleration phase, time to peak deceleration) and EMG (duration of
      agonist burst, duration of antagonist burst, time to antagonist burst) timing
      parameters decreased with increments of average velocity in a manner consistent
      with the variable timing error. In addition, the coefficient of variation for
      peak acceleration, peak deceleration, and integrated EMG of the agonist burst
      followed the same trend. Increasing average movement velocity also led to
      decreases in premotor and motor reaction times. Overall, the findings suggest a
      strong coherence between the variability of response outcome, kinematic, and EMG
      parameters.

PMID- 15140685
TI  - Matching of movements made independently by the two arms in normal humans.
AB  - Comparisons were made of voluntary movements of the right and left arms in normal
      human subjects. A series of movements of different amplitudes, made at the
      subject' own speed, was performed with one limb. After a rest period, the same
      series was repeated with the contralateral limb. The relation between movement
      peak velocity and movement amplitude was linear and was the same for both arms.
      With repeated testing over periods up to two months, the slope of the peak
      velocity-amplitude relation decreased during the first week, thereafter remaining
      unchanged. In a second series of experiments, six normal subjects continuously
      wore a 1 lb (0.45 kg) weight strapped to their left (non-dominant) forearm for up
      to 1 week. This resulted in an increase in the slope of the peak
      velocity/amplitude relation in this arm. A parallel change occurred in movements
      made independently by the right (non-loaded) arm. A similar matching of movement
      performance of the two limbs was seen following removal of the weight. The data
      is interpreted as proving support for the hypothesis that there is a single
      movement "command" which is applied to both limbs. The interaction of this
      command with the limbs which have similar second-order mechanical properties
      yields similar movements even when they are made independently.

PMID- 15140686
TI  - Intermanual interactions during simultaneous execution and programming of finger
      movements.
AB  - In bimanual movements, some differences between the movements performed by the
      two hands cause interference, while others do not. Similarly, in choice between
      responses with the left and right hand some differences between the two movements
      increase RT, while others do not. It is suggested that both kinds of effects are,
      at least in part, due to the incompatibility between processes that determine
      characteristics of movements jointly for both hands and that are present during
      preparation as well as during execution. This hypothesis implies that during
      execution of one movement, programming of a different movement to be performed
      with the other hand should be impaired, as compared to a condition in which the
      successive movements of both hands are the same. this expectation was confirmed
      for finger movements of different forms where an effect on choice RT had been
      shown previously. On the other hand, interference between execution and
      programming is not to be expected when successive movements differ in
      characteristics that are likely to be specified separately for each hand, as
      indicated by a lacking effect in choice experiments. This expectation was
      confirmed for successive movements performed with different fingers of either
      hand as compared to movements performed with the same fingers.

PMID- 15140687
TI  - Accommodation to increased accuracy demands by the right and left hands.
AB  - This study was designed to identify the phase of rapid aimed movements
      responsible for hand differences in motor skill, and to evaluate potential
      differences between the hands in accommodating to greater accuracy demands. In
      both experiments, an accelerometer mounted on a stylus allowed key changes in
      acceleration to be used to partition the movement into phases. In Experiment 1,
      slower left hand movement times were attributable primarily to a terminal homing
      in phase, especially as target size decreased. Since error rates varied as a
      function of hand and target size, speed-accuracy trade-offs may have occurred.
      Experiment 2 rigidly controlled error rate and confirmed the major hand
      difference to occur in the latter phase of the movement where error correction is
      presumed. Although less pronounced, adjustments were made in the earlier movement
      phases as well. Accommodation to greater accuracy demands involved moving the
      stylus closer to the target before decelerating to engage in error correction.
      This adjustment to gain enhanced precision was more pronounced in the left hand.

PMID- 15140688
TI  - The growth of stability: postural control from a development perspective.
AB  - This study compared central nervous system organizational processes underlying
      balance in children of three age groups: 15-31 months, 4-6 years, and 7-10 years,
      using a movable platform capable of antero-posterior (A-P) displacements or dorsi
      plantar flexing rotations of the ankle joint. A servo system capable of linking
      platform rotations to A-P sway angle allowed disruption of ankle joint inputs, to
      test the effects of incongruent sensory inputs on response patterns. Surface
      electromyography was used to quantify latency and response patterns. Surface
      electromyography was used to quantify latency and amplitude of the gastrocnemius,
      hamstrings, tibialis anterior, and quadriceps muscle responses. Cinematography
      provided biomechanical analysis of the sway motion. Results demonstrated that
      while directionally specific response synergies are present in children under the
      age of six, structured organization of the synergies is not yet fully developed
      since variability in timing and amplitude relationships between proximal and
      distal muscles is high. Transition from immature to mature response patterns was
      not linear but stage-like with greatest variability in the 4- to 6- year-old
      children. Results from balance tests under altered sensory conditions (eyes
      closed and/or ankle joint inputs altered) suggested that: (a) with development a
      shift in controlling inputs to posture from visual dependence to more adult-like
      dependence on a combination of ankle joint and visual inputs occurred in the 4-
      to 6-year-old, and reached adult form in the 7- to 10-year-old age group. It is
      proposed that the age 4-6 is a transition period in the development of posture
      control. At this time the nervous system (a) uses visual-vestibular inputs to
      fine tune ankle-joint proprioception in preparation for its increased importance
      in posture control and (b) fine tunes the structural organization of the postural
      synergies themselves.

PMID- 15140689
TI  - Reflex responses of human lip muscles to mechanical stimulation during speech.
AB  - The role played by reflex pathways in the production of movement has been a
      significant issue for motor control theorists interested in a wide variety of
      motor behaviors. From studies of locomotion and chewing, it appears that gains in
      reflex pathways can be altered so that activity in these pathways does not
      produce destabilizing responses during movement. In speech production, recent
      experimental evidence has been interpreted to suggest that autogenetic lip
      reflexes (perioral reflexes) are suppressed during sustained phonation or speech
      production. The present study was conducted to assess the effects of phonation,
      direction of movement, and ongoing speech production on reflex responses of lip
      muscles. The present results suggest, in contrast to earlier work, that this
      reflex pathway is not suppressed or absent because the amplitude of the observed
      response depends upon the activation levels of the various muscles of the lower
      lip and, therefore, indirectly on the nature of the gesture the subject is
      instructed to produce.

PMID- 15140690
TI  - Planning and preparing expected and unexpected movements: reexamining the
      relationships of arm, direction, and extent of movement.
AB  - Using variations of the movement precue method, this study sought to define the
      operational characteristics of motoric decisions that govern the planning and
      preparation of arm, direction, and extent of movement. Experiment 1 examined how
      these parameters are programmed when the precue method does not confound motoric
      and nonmotoric decision processes. Experiment 2 examined how an already planned
      and prepared response is modified (reprogrammed) when an unexpected response must
      be executed in its place. The collective results of both experiments demonstrated
      that (a) these parameters were planned and prepared in a specific order;
      knowledge about direction was necessary for the programming of arm or extent; (b)
      arm and extent were reprogrammed independently from direction but changes in
      direction caused all parameters to be reprogrammed, and (c) programming and
      reprogramming processes operated in a parallel mode when two or more parameters
      were involved. The results also showed that these parameters were organized
      within a hierarchical structure. The present findings were discussed in relation
      to those reported in previous precue studies and existing models of response
      programming.

PMID- 15140691
TI  - Reaction time methods in the study of motor programming: the precuing of hand,
      digit, and duration.
AB  - Recent reaction time analysis of motor programming has utilized a precue stimulus
      that provides advance information about some or all of the attributes for the
      upcoming motor response. This kind of precue typically confounds the number of
      remaining stimuli with the motoric processes under investigation (Zelaznik,
      1978). In Experiments 1 and 2 the precuing of hand, digit, and duration of a key
      press response was manipulated. A new precuing procedure was utilized that does
      not confound the number of stimuli with the motoric processes under
      investigation. The findings of Experiments 1 and 2 demonstrate that none of the
      advance information was helpful in reducing reaction time and as such, suggest
      that these features of movement are not selected in any particular order.
      Experiment 3 compared this new method of precuing to the other, traditional
      method. The results of this experiment suggested that there is parallel
      processing of the perceptual and motor mental operations in this reaction-time
      task, since there was an underadditive interaction between the number of stimulus
      response alternatives and the non-precued movement dimensions. This paper
      highlights problems inherent in the utilization of precursing methods to
      understand motor programming processes. It appears that a better understanding
      about the variables involved in movement control is necessary before examining
      the order of selection of those variables.

PMID- 15140692
TI  - Skill level, vision, and proprioception in simple one-hand catching.
AB  - Two experiments examined the interaction of vision and articular proprioception
      in simple one-hand catching. In Experiment 1 (N = 18) skilled baseball and
      softball players used the left and right hands to catch slowly moving tennis
      balls, while Experiment 2 (N = 16) used novice catchers as subjects. In half the
      trials, sight of the catching hand was prevented by placing a screen alongside
      the subjects' face. Results of Experiment 1 revealed that the screen caused
      minimal disruption of the positioning phase of the catch, with moderate
      disruption of the grasping phase. However, for the unskilled subjects of
      Experiment 2, the screen caused considerable disruption of positioning. The data
      provide only minimal support for Smyth and Marriott' (1982) contention that limb
      position is inadequately specified by articular proprioception. It is argued that
      skill level serves as a mediator in the ability to use proprioception for limb
      positioning, but vision appears necessary to control the precise temporal
      organization of the grasp phase of one-hand catching.

PMID- 15140693
TI  - On the relationship between peak force and peak force variability in isometric
      tasks.
AB  - An experiment is reported documenting the relationship between peak force and
      peak force variability with a fixed criterion time to peak force for an isometric
      task requiring activation of the elbow flexors. The results show that maximum
      peak force increases with increments in time to peak force and that peak force
      variability increases with increments of peak force in an exponential type
      function. Furthermore, despite the presence of peak force and time to peak force
      feedback, subjects systematically shifted time to peak force as a function of the
      percentage of peak force being produced. This temporal modulation changes the
      percentage of peak force represented by any given peak force criterion. When peak
      force is made proportional to the degree of departure from the criterion time to
      peak force, a linear relationship is found between peak force and peak force
      variability. These findings suggest that time to peak force and rate of force
      production are parameters that influence veridical estimates of the force
      variability function.

PMID- 15140694
TI  - Reproducing the end location of a positioning movement: the long and short of it.
AB  - Two experiments were conducted in an attempt to determine the conditions under
      which shifts in the starting position of a linear positioning response influenced
      the reproduction of the end location of movements of various lengths. In
      Experiment 1, response bias (i.e., shift in constant error) was affected by the
      direction of the shift in starting position between presentation and recall. For
      short (20 cm) and medium (50 cm) length movements, this relationship was evident
      regardless of hand used (left or right), direction of the movement (left to right
      or right to left), and length of the retention interval (5 or 45 s). However, no
      relation between response bias and the direction of the starting position shifts
      was apparent for long (80 cm) movements. The results of Experiment 2 in which
      more movement lengths were used revealed a response bias that corresponded to
      shifts in starting position primarily during the first few reproductions of the
      two shortest movements (20 and 30 cm). However, no systematic bias was evident
      for any length movement after three reproduction attempts. Possible strategies
      used by subjects to reproduce the end location of movements of various lengths
      were discussed.

PMID- 15140695
TI  - A note on the natural basis of action categories: the catching distance of
      mantids.
AB  - What is the basis for the categorical distinctions evident in action? For some
      visually-guided activities it can be shown that categories of action are
      specified by criterial values of optical properties. In the more general case,
      the criterial optical properties should be scaled relative to dimensions of the
      acting animal. The analysis of the prey-catching behavior of praying mantids is
      used to exemplify the strategy for determining naturally defined boundaries on
      actions.

PMID- 15140696
TI  - Mathematical models of central pattern generators in locomotion: I. Current
      problems.
AB  - As a background for subsequent studies of mathematical models of central pattern
      generators in locomotion (Stafford & Barnwell, 1985a, b) relevant aspects of the
      literature on locomotion are reviewed, concepts of locomotion discussed, and
      extant models considered. Advantages and disadvantages of present models are
      discussed, and the need for mathematical models is emphasized. It is shown that
      realistic models of pattern generation in locomotion must take numerous factors
      into account, including phases of step cycle, muscle sequencing, gait and
      interlimb coordination, initiation and cessation of locomotion, and many aspects
      of neuromuscular control and function.

PMID- 15140697
TI  - Mathematical models of central pattern generators in locomotion: II. Single limb
      models for locomotion in the cat.
AB  - Three mathematical models of central pattern generation for locomotion in the
      single limb of the cat are presented. In each model, the activities in
      populations of neurons controlling limb joint flexors and extensors are described
      by a system of nonlinear differential equations. Each solution of the system for
      a different set of parameters corresponds to a simulation of some gait of the
      cat. Model I is based on unit generators for each limb joint muscle group and
      assumes that flexors inhibit their paired extensors, but not vice-versa. Model
      IIa assumes that flexors and extensors are mutually inhibitory, but that only the
      flexors have inherent oscillatory capability. Model IIb assumes flexors and
      extensors are mutually inhibitory and that both flexors and extensors have
      oscillatory capability. The properties of each of these models are explored,
      compared and contrasted, and discussed in relation to the experimental
      literature. All three models are shown to be capable of generating patterns
      consistent with various stepping rates of the cat and to show appropriate muscle
      sequencing and flexor-extensor interactions. Further, all three models exhibit
      smooth initiation and termination of stepping. However, Model I seems to provide
      a more parsimonious account of producing changes in stepping rate and is
      preferred, therefore, over models IIa and IIb.

PMID- 15140698
TI  - Mathematical models of central pattern generators in locomotion: III. Interlimb
      model for the cat.
AB  - Possible neural connective patterns and functions with respect to interlimb
      coordination are studied theoretically with a mathematical model of the central
      pattern generating system for cat locomotion. Activities in populations of
      neurons controlling limb joint flexors and extensors in all four limbs are
      represented by a system of nonlinear differential equations. Solutions of the
      system for various parameter values simulate various gaits of the cat. The model
      is shown to be capable of generating all gaits of the cat and accounting for
      corresponding phase changes in interlimb coordination. The model also exhibits
      smooth changes of gait, and smooth initiation and termination of stepping.
      Further, within each limb, muscle sequencing, step cycle phases, and flexor
      extensor interactions can be studied. The model suggests that one of the simplest
      mechanisms for a central command system to change the gait is via inhibition of
      specific interlimb propriospinal pathways. In a final section, properties of both
      proposed single limb and interlimb models are reviewed with specific reference to
      planning future experimental and theoretical studies.

PMID- 15140699
TI  - Fitts' Law in two dimensions with hand and head movements.
AB  - Subjects performed two-dimensional discrete movements either with a helmet
      mounted sight or with a joystick. Fitts' Law was found to be a good predictor of
      the speed-accuracy tradeoff for both systems. The joystick produced faster
      movement times than the helmet-mounted sight. For both systems, horizontal and
      vertical movements were slightly faster than diagonal movements. Two dimensional
      generalizations of Fitts' Law were discussed in terms of multidimensional
      scaling. The obtained pattern of movement times was found to be intermediate to
      the predictions of Euclidean and City-block models of the movement space. Muscle
      coordination strategies were considered, and a strictly serial coordination model
      was rejected. A strictly parallel model was also rejected for the helmet-mounted
      sight, but not for the joystick.

PMID- 15140700
TI  - Achilles tendon reflexes and surface EMG activity during anticipation of a
      significant event and preparation for a voluntary movement.
AB  - Achilles tendon reflexes were evoked bilaterally during and shortly after an
      interstimulus-interval (ISI) of 4 s and expressed as percentages of an averaged
      control reflex. Surface EMG of the soleus muscles were recorded continuously
      during the ISI, and expressed as percentages of a control EMG level. Three types
      of tasks were introduced, according to a between subjects design. Condition I
      consisted of a guessing task, involving anticipation of the second stimulus (S2)
      and not requiring a motor response. Conditions II and III were a warned choice
      and simple RT task respectively, the motor response to S2 being a plantar flexion
      of either the left or right foot in Condition II, and a plantar flexion of the
      right foot in Condition III. The results can be stated as follows: 1.
      Anticipation of a stimulus is not sufficient for a reflex increase to occur
      during an ISI. Preparation for a movement seems to be a necessary condition. 2.
      The reflex increase during preparation is rather independent of the amount of
      selectivity in the preparatory process; simple and choice RT tasks yield similar
      results, although the mean RTs do differ. 3. A difference between the involved
      and non-involved legs in the simple RT task is not found in the present
      experiment, as opposed to other studies. The particular instruction given to the
      subjects could be of importance in producing this difference. 4. Reflex changes
      cannot simply be accounted for by changes in background EMG of the agonist, as
      the EMG time course shows no changes over time in either condition.

PMID- 15140701
TI  - Sensory feedback in the learning of a novel motor task.
AB  - The role of different forms of feedback is examined in learning a novel motor
      task. Five groups of ten subjects had to learn the voluntary control of the
      abduction of the big toe, each under a different feedback condition
      (proprioceptive feedback, visual feedback, EMG feedback, tactile feedback, force
      feedback). The task was selected for two reasons. First, in most motor learning
      studies subjects have to perform simple movements which present hardly any
      learning problem. Second, studying the learning of a new movement an provide
      useful information for neuromuscular reeducation, where patients often also have
      to learn movements for which no control strategy exists. The results show that
      artificial sensory feedback (EMG feedback, force feedback) is more powerful than
      "natural" (proprioceptive, visual, and tactile) feedback. The implications of
      these results for neuromuscular reeducation are discussed.

PMID- 15140702
TI  - The next step: anatomy of the white matter.

PMID- 15140704
TI  - Anatomic dissection tractography: a new method for precise MR localization of
      white matter tracts.
AB  - BACKGROUND AND PURPOSE: Several white matter tracts in the brain cannot be
      identified on MR studies because they are indistinguishable from the surrounding
      white matter. We sought to develop a method to precisely localize white matter
      tracts by correlating anatomic dissections with corresponding MR images. METHODS:
      MR imaging was used to guide anatomic dissection of the uncinate fasciculus.
      Formalin-preserved brains were imaged before and after several stages of
      dissection. Progressive dissection was guided by using volume-rendered and cross
      sectional images of the dissected specimens. To precisely define the location of
      a tract, its surface was traced on the corresponding three-dimensional MR image
      of the dissected specimen. MR images of the dissected and intact specimens were
      coregistered to allow the tracings to be projected onto multiplanar reformatted
      images of the intact specimen. RESULTS: The uncinate fasciculus in the anterior
      temporal lobe and external and extreme capsules was dissected without destroying
      adjacent structures. Coregistration of the MR images from intact and dissected
      specimens permitted precise MR identification of the surface of this tract. These
      methods were successful for two additional tracts. (The dissected anatomy, MR
      anatomy, and clinical examples of the three tracts are described in a companion
      article.) CONCLUSION: MR-assisted anatomic dissection permits limited removal of
      brain tissue so that important anatomic and surgical relationships can be
      demonstrated on correlated MR studies. This method can be applied to other white
      matter tracts that are indistinguishable on MR studies and to situations in which
      anatomic validation of normal and abnormal diffusion tractographic studies is
      needed.

PMID- 15140705
TI  - MR imaging of the temporal stem: anatomic dissection tractography of the uncinate
      fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic
      radiation.
AB  - BACKGROUND AND PURPOSE: The MR anatomy of the uncinate fasciculus, inferior
      occipitofrontal fasciculus, and Meyer's loop of the optic radiation, which
      traverse the temporal stem, is not well known. The purpose of this investigation
      was to study these structures in the anterior temporal lobe and the external and
      extreme capsules and to correlate the dissected anatomy with the cross-sectional
      MR anatomy. METHODS: Progressive dissection was guided by three-dimensional MR
      renderings and cross-sectional images. Dissected segments of the tracts and the
      temporal stem were traced and projected onto reformatted images. The method of
      dissection tractography is detailed in a companion article. RESULTS: The temporal
      stem extends posteriorly from the level of the amygdala to the level of the
      lateral geniculate body. The uncinate and inferior occipitofrontal fasciculi pass
      from the temporal lobe into the extreme and external capsules via the temporal
      stem. Meyer's loop extends to the level of the amygdala, adjacent to the uncinate
      fasciculus and anterior commissure. These anatomic features were demonstrated on
      correlative cross-sectional MR images and compared with clinical examples.
      CONCLUSION: This study clarified the MR anatomy of the uncinate and inferior
      occipitofrontal fasciculi and Meyer's loop in the temporal stem and in the
      external and extreme capsules, helping to explain patterns of tumor spread. The
      inferior occipitofrontal fasciculus is an important yet previously neglected
      tract. These results provide a solid anatomic foundation for diffusion
      tractography of the normal temporal stem and its tracts, as well as their
      abnormalities in brain disorders such as epilepsy, postoperative complications,
      trauma, schizophrenia, and Alzheimer disease.

PMID- 15140706
TI  - Water diffusion compartmentation at high b values in ischemic human brain.
AB  - BACKGROUND AND PURPOSE: We studied the evolution of brain water compartments
      during the early stage of ischemic stroke. METHODS: Diffusion-weighted imaging
      was performed at 1.5 T in 10 volunteers and 14 patients with stroke. We used a
      single-shot echo-planar technique with 11 b values of 0-5000 s/mm(2). Regions of
      interest were selected in the white matter (WM) and striatum of the volunteers
      and in the ischemic core of the patients. Measurements were fitted on the basis
      of a biexponential decay with the b factor as follows: S(b) = S(0)[(f(slow) x
      exp(-b x ADC(slow)) + (f(fast) x exp(-b x ADC(fast))] where S(b) is the signal
      intensity in the presence of a diffusion gradient, S(0) is the signal intensity
      without diffusion sensitization, ADC(slow) and ADC(fast) are the respective
      apparent diffusion coefficients (ADCs) of slow diffusing compartments (SDCs) and
      fast diffusing compartments (FDCs), and f(slow) and f(fast) the respective
      contributions to the signal intensity of SDC and FDC. RESULTS: In healthy
      subjects, FDC represents 74.3 +/- 3.1% of brain water, with ADC(fast) = (124.6 +/
      12.0) x 10(-5) mm(2)/s and ADC(slow) = (15.5 +/- 3.9) x 10(-5) mm(2)/s. In
      stroke, decreased FDC (49.1% +/- 10.9%; P = 1.05 x10(-5)) and increased ADC(slow)
      ([22.4 +/- 8.1] x 10(-5) mm(2)/s; P = 8.07 x 10(-3)) were observed, but ADC(fast)
      was not significantly changed ([135.6 +/- 25.7] x 10 (-5) mm(2)/s; P =.151).
      CONCLUSION: The restricted diffusion observed in the early stroke is mainly
      related to a redistribution of water from the FDC to the SDC.

PMID- 15140708
TI  - Evolution of lesions in Susac syndrome at serial MR imaging with diffusion
      weighted imaging and apparent diffusion coefficient values.
AB  - BACKGROUND AND PURPOSE: Susac syndrome is a rare disorder consisting of
      encephalopathy, hearing loss, and retinal arteriolar occlusions. The purpose of
      this study was to evaluate the evolution of lesions in this disease by using
      serial MR imaging with diffusion-weighted imaging (DWI) and apparent diffusion
      coefficients (ADCs). Abnormalities in the nonlesional white matter (NLWM) were
      also analyzed. METHODS: Serial MR and DWI findings in two patients with Susac
      syndrome were reviewed retrospectively. ADCs of the lesions and the NLWM were
      compared with values of the corresponding anatomical regions in 16 control
      subjects. RESULTS: T2-weighted images, DWIs, and fluid-attenuated inversion
      recovery (FLAIR) images demonstrated diffuse small hyperintense lesions
      predominantly involving the corpus callosum, white matter, cerebral cortex, and
      deep gray structures. During the whole course in the two patients, 437, 295, and
      113 lesions were depicted on FLAIR images, T2-weighted images, and DWIs,
      respectively. With the aggravation and mitigation of the clinical symptoms, the
      size and number of the lesions changed over time. Of 65 lesions with measured
      ADCs, six had restricted ADCs (5.29-6.91 x 10(-4) mm(2)/s), and 29 had elevated
      ADCs (8.02-13.5 x 10(-4) mm(2)/s). With disease progression, ADCs in the NLWM
      changed from normal to elevated; this corresponded to the diffuse signal
      intensity change seen in the white matter. CONCLUSION: FLAIR imaging is the most
      sensitive sequence for detecting lesions of Susac syndrome. DWI is useful in
      demonstrating the heterogeneous nature of lesions, depicting occult abnormalities
      in the white matter, elucidating underlying pathologic processes, and conducting
      patient follow-up.

PMID- 15140707
TI  - Evolution of water diffusion and anisotropy in hyperacute stroke: significant
      correlation between fractional anisotropy and T2.
AB  - BACKGROUND AND PURPOSE: We hypothesized that, in acute cerebral ischemic stroke,
      anisotropic diffusion increases if T2 signal intensity is not substantially
      elevated and decreases once T2 hyperintensity becomes apparent. Our purpose was
      to correlate fractional anisotropy (FA) measurements with the clinical time of
      stroke onset, apparent diffusion coefficients (ADC), and T2 signal intensity.
      METHODS: Tensor diffusion-weighted images (DWIs) of 25 patients were obtained
      within 12 hours of symptom onset. Trace DWIs, ADCs, FAs, and echo-planar T2
      weighted images (T2WI) were generated. Stroke and contralateral normal volumes of
      interest (VOIs) were outlined on DWIs and projected onto the inherently
      coregistered ADC map, FA map, and echo-planar T2WI. Mean signal intensity of the
      ischemic and contralateral normal VOIs were compared for relatives change in ADC,
      FA, and signal intensity on T2WIs. RESULTS: A significant negative correlation
      was observed between FA and T2 signal-intensity change (r = -0.61, P =.00009). A
      trend of correlation between FA signal intensity and time of onset were found (r
      = -0.438, P =.025). No significant correlation was found between ADC and FA
      values (r = -0.302, P =.134). The mean ADC reduction in the ipsilateral ischemic
      volume was 31% +/- 11 compared with the contralateral normal side. CONCLUSION:
      Change in FA is inversely correlated with T2 signal intensity and, to a lesser
      extent, the time of onset, but it is not well correlated with ADC values in the
      acute stage.

PMID- 15140709
TI  - Frequency of asymptomatic microbleeds on T2*-weighted MR images of patients with
      recurrent stroke: association with combination of stroke subtypes and
      leukoaraiosis.
AB  - BACKGROUND AND PURPOSE: Asymptomatic microbleeds shown by T2*-weighted MR imaging
      are associated with small-artery diseases, especially with intracerebral
      hemorrhage. Few studies have focused on the prevalence of microbleeds in patients
      with recurrent stroke. We investigated frequency of microbleeds in patients with
      recurrent stroke and association of presence of microbleeds with a combination of
      stroke subtypes and severity of leukoaraiosis. METHODS: The study population
      consisted of 102 patients with primary stroke and 54 patients with recurrent
      stroke. Microbleeds were counted and classified by using T2*-weighted MR imaging
      with a 1.0-T system. RESULTS: Patients with recurrent stroke showed a
      significantly higher prevalence of microbleeds (68.5%) than did patients with
      primary stroke (28.4%) (P <.0001). Among patients with recurrent stroke, the
      highest frequency of microbleeds occurred in those with intracerebral hemorrhage
      alone (92.3%), with the next highest frequency occurring in those with a
      combination of intracerebral hemorrhage and ischemic stroke (76.5%) and then
      those with ischemic stroke alone (50.0%) (P <.05). Leukoaraiosis was more severe
      in patients with recurrent stroke than in patients with primary stroke, and
      correlations between grade of microbleeds and severity of leukoaraiosis were
      found in patients with primary stroke (r = 0.367, P <.001) and in patients with
      recurrent stroke (r = 0.553, P <.0001). Logistic regression analysis identified
      recurrent stroke (odds ratio, 4.487; 95% confidence interval, 1.989-10.120) and
      leukoaraiosis (odds ratio, 5.079; 95% confidence interval, 2.125-12.143) as being
      significantly and independently associated with microbleeds. CONCLUSION:
      Asymptomatic microbleeds are observed to occur frequently in patients with
      recurrent stroke, either hemorrhagic or ischemic stroke, and are closely
      associated with the severity of leukoaraiosis.

PMID- 15140711
TI  - Volumetric proton spectroscopic imaging of mild traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: Poor clinical outcomes without notable neuroimaging
      findings after mild traumatic brain injury (MTBI) suggest diffuse tissue damage
      and altered metabolism not observable with conventional MR imaging and CT. In
      this study, MTBI-associated metabolic changes were assessed over the entire brain
      by using volumetric proton MR spectroscopic imaging (MRSI) and the findings
      related to injury and outcome assessments. METHODS: Fourteen subjects with mild
      closed head injury (Glasgow Coma Scale [GCS] scores of 13-15) underwent
      structural MR imaging and proton MRSI at 1.5 T within 1 month of injury.
      Distributions of N-acetylaspartate (NAA), total creatine (Cr), and total choline
      (Cho) were mapped over a wide region of the brain, and metabolite ratios were
      calculated for 25 regions without MR imaging abnormalities. Results were compared
      with data from 13 control subjects. RESULTS: Significant changes (P <.05) were
      found for some, but not all, brain regions for the average values from all MTBI
      subjects, with reduced NAA/Cr, increased Cho/Cr, and reduced NAA/Cho. Global
      NAA/Cho obtained from the sum of all sampled regions in two subjects was
      significantly reduced. Metabolite ratios were not significantly correlated with
      GCS score at admission or Glasgow Outcome Scale (GOS) score at 6 months after
      injury, although they were weakly correlated with GOS score at discharge.
      CONCLUSION: These results show evidence of widespread metabolic changes following
      MTBI in regions that appear normal on diagnostic MR images. Although the
      association with injury assessment and outcome is weak, this preliminary study
      demonstrates the applicability of volumetric proton MRSI for evaluating diffuse
      injury associated with MTBI.

PMID- 15140710
TI  - Dynamic perfusion CT: optimizing the temporal resolution and contrast volume for
      calculation of perfusion CT parameters in stroke patients.
AB  - BACKGROUND AND PURPOSE: Numerous parameters are involved in dynamic perfusion CT
      (PCT). We assessed the influence of the temporal sampling rate and the volume of
      contrast material. METHODS: Sixty patients with ischemic hemispheric stroke
      lasting > or = 12 hours underwent PCT. Groups of 15 patients each received 30,
      40, 50, or 60 mL of contrast agent. Regional cerebral blood volume (rCBV),
      regional cerebral blood flow (rCBF), mean transit time (MTT), and time-to-peak
      (TTP) maps were calculated for temporal sampling intervals of 0.5, 1, 2, 3, 4, 5,
      and 6 seconds. Results were statistically compared. Signal-to-noise ratios
      (SNRs), duration of arterial entrance to venous exit, and radiation dose were
      also assessed. RESULTS: Increasing temporal sampling intervals lead to
      significant overestimation of rCBV, rCBF, and TTP and significant underestimation
      of MTT compared with values for an interval of 1 second. Maximal allowable
      intervals to avoid these effects were 2, 3, 3, and 4 seconds for 30, 40, 50, and
      60-mL boluses, respectively. Venous exit of contrast material occurred in 97.5%
      of patients after 36, 42, 42, and 48 seconds, respectively, for the four volumes.
      SNRs did not differ with volume. The effective radiation dose varied between
      0.852 and 1.867 mSv, depending on the protocol. The cine mode with two 40-mL
      boluses and the toggling-table technique with one 60-mL bolus had the lowest
      doses. CONCLUSION: Temporal sampling intervals greater than 1 second can be used
      without altering the quantitative accuracy of PCT. Increased sampling intervals
      reduce the radiation dose and may allow for increased spatial coverage.

PMID- 15140712
TI  - A prospective functional MR imaging study of mild traumatic brain injury in
      college football players.
AB  - BACKGROUND AND PURPOSE: Although concussion is common among athletes, evidence
      based methods for clinical evaluation, treatment, and recovery are lacking. We
      used a prospective, functional neuroimaging approach to assess sports-related
      concussion in which imaging was performed before injury so that brain changes
      resulting from concussion could be better understood. METHODS: Neurophysiologic
      correlates of sports-related concussion were investigated in eight college
      football players by using functional MR imaging. Preseason baseline levels of
      blood oxygen level-dependent (BOLD) activity were acquired during the performance
      of a test battery that included mathematical, memory, and sensorimotor
      coordination tasks. Four players who had a concussion repeated these baseline
      procedures within 1 week of injury. The remaining control players were retested
      at the end of the season. RESULTS: Specific neural signatures of concussion were
      detected in individual players by comparing postconcussion results to
      preconcussion baseline values. The validity of these indicators was confirmed by
      comparing them with the same measures in noninjured control subjects. When
      compared with control subjects, concussed players had marked within-subject
      increases in the amplitude and extent of BOLD activity during a finger-sequencing
      task. Effects were observed primarily in the parietal and lateral frontal and
      cerebellar regions. CONCLUSION: Differences in neural functioning were observed
      in the absence of observed deficits in behavioral performance, suggesting that
      this approach may increase sensitivity to concussion compared with
      neuropsychological evaluation alone. Though preliminary, the proposed prospective
      neuroimaging approach may have great potential for understanding mild traumatic
      brain injury and identifying mechanisms underlying recovery.

PMID- 15140713
TI  - Comparison of cerebral blood volume and vascular permeability from dynamic
      susceptibility contrast-enhanced perfusion MR imaging with glioma grade.
AB  - BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular
      permeability (K(trans)) permit in vivo assessment of glioma microvasculature. We
      assessed the associations between rCBV and K(trans) derived from dynamic,
      susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and
      between rCBV and K(trans). METHODS: Seventy-three patients with primary gliomas
      underwent conventional and DSC MR imaging. rCBVs were obtained from regions of
      maximal abnormality for each lesion on rCBV color maps. K(trans) was derived from
      a pharmacokinetic modeling algorithm. Histopathologic grade was compared with
      rCBV and K(trans) (Tukey honestly significant difference). Spearman and Pearson
      correlation factors were determined between rCBV, K(trans), and tumor grade. The
      diagnostic utility of rCBV and K(trans) in discriminating grade II or III tumors
      from grade I tumors was assessed by logistic regression. RESULTS: rCBV was
      significantly different for all three grades (P </=.0005). K(trans) was
      significantly different between grade I and grade II or III (P =.027) but not
      between other grades or combinations of grades. Spearman rank and Pearson
      correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r =
      0.771; K(trans) and grade, r = 0.234 and r = 0.277; and rCBV and K(trans), r =
      0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas
      (P <.0001). CONCLUSION: rCBV with strongly correlated with tumor grade; the
      correlation between K(trans) and tumor grade was weaker. rCBV and K(trans) were
      positively but weakly correlated, suggesting that these parameters demonstrate
      different tumor characteristics. rCBV is a more significant predictor of high
      grade glioma than K(trans).

PMID- 15140715
TI  - Diagnostic value of contrast-enhanced fluid-attenuated inversion recovery MR
      imaging of intracranial metastases.
AB  - BACKGROUND AND PURPOSE: Postcontrast fluid-attenuated inversion recovery (FLAIR)
      imaging effectively depicts parenchymal and leptomeningeal metastases, as
      reported in limited patient groups. We compared postcontrast T1-weighted (T1W)
      and FLAIR imaging in a larger group. METHODS: Sixty-nine patients with known
      malignancy and suspected cranial metastases underwent axial FLAIR and spin-echo
      T1W imaging with and then without intravenous gadopentetate dimeglumine.
      Postcontrast images were compared for lesion conspicuity and enhancement, number
      of parenchymal metastases, and extension of leptomeningeal-cisternal metastases.
      RESULTS: Parenchymal metastases were demonstrated in 33 patients. Compared with
      T1W images, postcontrast FLAIR images showed more metastases in five patients, an
      equal number in 20, and fewer lesions in eight. Regarding lesion conspicuity,
      postcontrast FLAIR imaging was superior in five patients, equal in one, and
      inferior in 27. For enhancement, FLAIR imaging was superior in five, equal in
      five, and inferior in 23. Superior FLAIR results for lesion number, conspicuity,
      and enhancement were observed in the same five patients; in these patients, FLAIR
      imaging was performed as the second postcontrast sequence. Eleven patients had
      leptomeningeal-cisternal metastases; lesion conspicuity, extension, and
      enhancement were superior on postcontrast FLAIR images in eight. In five of eight
      patients, FLAIR imaging was performed as the second postcontrast sequence. Four
      patients had cranial-nerve metastases; in three, postcontrast FLAIR imaging was
      superior for lesion conspicuity and extension. In two of these patients, FLAIR
      imaging was the second postcontrast sequence. CONCLUSION: Postcontrast FLAIR
      imaging is a valuable adjunct to postcontrast T1W imaging. Precontrast and
      postcontrast FLAIR imaging effectively delineates parenchymal metastases,
      particularly leptomeningeal-cisternal and cranial-nerve metastases.

PMID- 15140714
TI  - Susceptibility-based imaging of glioblastoma microvascularity at 8 T: correlation
      of MR imaging and postmortem pathology.
AB  - BACKGROUND AND PURPOSE: Imaging methods are currently being optimized in an
      attempt to assess and monitor angiogenesis in vivo. The purpose of this
      investigation was to determine whether areas of apparently increased tumor
      vascularity, as identified on 8-T gradient-echo (GE) imaging of a known
      glioblastoma multiforme (GBM), corresponds to foci of increased microvascularity
      on histopathologic analysis. METHODS: We performed postmortem in situ, high
      resolution GE 8-T MR imaging of the brain in a 53-year-old woman with GBM. Ten
      histopathologic specimens in the region of the tumor bed were studied by using
      hematoxylin-eosin and reticulin stains. MR and histopathologic results were
      assessed and compared for microvascular size and density. RESULTS: 8-T GE images
      showed small, penetrating vessels in the gray matter and white matter. The
      images, however, were partly inhomogeneous as a result of local magnetic field
      inhomogeneities adjacent to the skull base and aerated paranasal sinus
      structures. 8-T MR images demonstrated serpiginous areas of signal intensity
      loss, which were thought to represent areas of increased microvascularity. Areas
      of lower microvascularity in the tumor bed corresponded to areas of lower
      vascularity on histopathologic sections with smaller vessel diameters. There was
      concurrence between vascular size predicted by histopathologic analysis and 8-T
      MR imaging in nine of nine biopsy samples. Vascular density agreed in seven of
      nine biopsy samples. CONCLUSION: Our pilot data suggest that microvascularity in
      GBM can be identified by use of high-resolution, GE, 8-T MR imaging.

PMID- 15140716
TI  - Degenerative thalamic hamartoma: CT and MR imaging features.
AB  - We describe hamartomas of possible thalamic origin. CT revealed marked
      calcification in the mass lesion, and MR imaging revealed contrast enhancement.
      Histologically, outgrowth of the glia was observed, but no neoplastic component
      was confirmed. Immunohistochemical staining was positive for the cell-adhesion
      factor N-CAM and negative for polysialic acid.

PMID- 15140717
TI  - Multisection CT angiography compared with catheter angiography in diagnosing
      vertebral artery dissection.
AB  - BACKGROUND AND PURPOSE: Multisection CT angiography is a minimally invasive
      technique that can provide high-resolution and high-contrast images of the
      arterial lumen and wall. To our knowledge, the ability of multisection CT
      angiography in detecting vertebral artery (VA) dissection has never been
      evaluated. We assessed the sensitivity and specificity of a routine,
      standardized, multisection CT angiographic protocol for the detection of VA
      dissection. METHODS: We retrospectively reviewed multisection CT angiograms of 17
      patients with VA dissection and 17 control subjects. The acquisition protocol for
      multisection CT angiography was 1.25-mm nominal section thickness, a table speed
      of 7.5 mm per rotation (9.4 mm/s), and a 0.8-second gantry rotation period. Two
      radiologists assessed the maximum intensity projection and axial source images.
      The sensitivity and specificity of this technique in depicting VA dissection were
      determined. RESULTS: Conventional angiography depicted 15 normal and 19 dissected
      VAs (including five stenotic, seven occlusive, and seven aneurysmal dissections)
      in the patient group and 28 normal and six atherosclerotic VAs in the control
      group. Multisection CT angiography enabled successful diagnosis of all 19
      dissected VAs and 48 (98%) of 49 nondissected VAs but misidentified a severe
      atherosclerotic lesion as an aneurysmal-type dissection. The sensitivity,
      specificity, accuracy, and positive and negative predictive values of
      multisection CT angiography in diagnosing VA dissection were 100%, 98%, 98.5%,
      95%, and 100%, respectively. CONCLUSION: Multisection CT angiography was a
      sensitive and accurate technique for the diagnosis of VA dissection.

PMID- 15140718
TI  - Doppler sonographic evaluation of shunts in patients with dural arteriovenous
      fistulas.
AB  - BACKGROUND AND PURPOSE: Doppler sonography has been used to assess global
      cerebral circulation time (CCT) in healthy volunteers and a small number of
      patients with cerebral arteriovenous malformations. We evaluated the effect of
      arteriovenous shunts on global CCT in patients with dural arteriovenous fistulas
      (DAVFs) by using this Doppler echo contrast-bolus tracking test. METHODS: We
      measured CCT as the time delay in a contrast bolus to the internal carotid artery
      (ICA) and internal jugular vein (IJV) in 13 patients with DAVF and 30 age-matched
      control subjects. Mean CCT and mean arterial and venous rise times (Delta t = 80%
      of total signal-intensity increase) were compared. Posttreatment follow-up
      measurements were performed in five patients. RESULTS: Mean CCT and venous Delta
      t were significantly different between patients and controls (CCT, 1.1 +/- 0.9 vs
      6.9 +/- 1.2 seconds, P <.0001; venous Delta t, 5.2 +/- 2.0 vs 7.0 +/- 2.6
      seconds, P =.024), but arterial Delta t values were not (4.4 +/- 1.8 vs 4.7 +/-
      2.0 seconds). Posttreatment follow-up of two occluded fistulas showed CCT
      normalization. One near-occlusion showed a two-step increase in signal intensity,
      and incomplete occlusion in two patients left the CCT unchanged. One patient with
      an extracranial, highly vascularized glomus tumor draining into the IJV had a CCT
      of 1.8 seconds. CONCLUSION: In DAVF patients, sonographic CCT is significantly
      shortened. Our test is highly sensitive for arteriovenous shunts but not specific
      for DAVF alone. Follow-up measurements in DAVF patients are well correlated with
      results of angiographic treatment. CCT assessment might become an additional tool
      for evaluating these patients and monitoring their treatment.

PMID- 15140719
TI  - Primitive vertebrobasilar system associated with a ruptured aneurysm.
AB  - Persistent primitive lateral vertebrobasilar (PPLVB) anastomosis is a rare
      remnant of early fetal development whose occurrence, to our knowledge, has been
      reported only once. We now report a new variant in which the basilar artery was
      fed primarily by a PPLVB anastomosis because on one side the vertebrobasilar
      junction was incompletely developed and on the other it was aplastic. Aneurysmal
      rupture in this case may be attributable to excessive hemodynamic stress.

PMID- 15140720
TI  - Multiple cerebral aneurysms in factor VII deficiency.
AB  - A rare case of multiple cerebral aneurysms and factor VII deficiency is
      presented. The authors hypothesize a possible combined genetic defect similar to
      that of other conditions with clotting disorders. Different treatment options are
      discussed for factor VII deficiency in particular and multiple cerebral aneurysms
      in general. The authors advise treatment of all detected aneurysms in case of a
      subarachnoid hemorrhage rather than only treatment of the ruptured aneurysms in
      order to immediately start the so-called triple-H therapy.

PMID- 15140721
TI  - Multisection CT venography of the dural sinuses and cerebral veins by using
      matched mask bone elimination.
AB  - Matched mask bone elimination (MMBE) is a technique for the automatic removal of
      bone pixels from CT angiography data sets. We describe the use of this technique
      in two patients with the clinical suspicion of dural sinus thrombosis. We
      conclude that multisection CT venography with MMBE is a useful adjunct for the
      visualization of the intracranial venous circulation by removing bone from the
      image. In contrast to techniques described previously, MMBE is fully automated
      and operator independent.

PMID- 15140722
TI  - Diffusion-weighted MR imaging findings of acute necrotizing encephalopathy.
AB  - Multiple, symmetrical brain lesions affecting the bilateral thalami and cerebral
      white matter, which often show a concentric structure on CT and MR images,
      characterize acute necrotizing encephalopathy (ANE) of childhood. We describe the
      imaging findings of a 2-year-old child with ANE obtained with diffusion-weighted
      MR imaging. We discuss the significance of these findings, as well as the
      pathophysiology of ANE lesions, with reference to the appearance of the disease
      as revealed by diffusion-weighted MR imaging.

PMID- 15140723
TI  - Influenza-associated encephalitis/encephalopathy with a reversible lesion in the
      splenium of the corpus callosum: a case report and literature review.
AB  - We report the cases of two patients with influenza-associated
      encephalitis/encephalopathy (IAEE) who presented with mild CNS manifestations and
      complete recovery within a few days. Initial MR imaging at days 4 and 5 revealed
      a lesion in the central portion of the splenium of the corpus callosum with a
      reduced apparent diffusion coefficient (ADC) value, which completely resolved on
      follow-up studies at day 10. We postulate two possible mechanisms for decreased
      ADC; namely, intramyelinic edema and an inflammatory infiltrate.

PMID- 15140724
TI  - Brain stem hypertensive encephalopathy evaluated by line scan diffusion-weighted
      imaging.
AB  - Hypertensive encephalopathy rarely presents with predominant involvement of the
      brain stem and relative sparing of the supratentorial regions. We describe the MR
      imaging features in a patient with reversible brain stem hypertensive
      encephalopathy. Extensive hyperintensity was predominantly seen in brain stem
      regions on fluid-attenuated inversion-recovery and T2-weighted images. These
      lesions showed an increased apparent diffusion coefficient with the use of line
      scan diffusion-weighted imaging. The clinical findings and MR imaging
      abnormalities resolved with control of hypertension.

PMID- 15140725
TI  - MR findings in Hashimoto encephalopathy.
AB  - A 35-year-old Korean woman had Hashimoto encephalopathy of varying MR imaging
      appearance over 5 years that ranged from that of transient subcortical ischemia
      to that of gradually evolving multifocal signal intensity change accompanied by
      unilateral cerebellar atrophy. Thus, the MR imaging appearance of Hashimoto
      encephalopathy may simulate an ischemic stroke, multiple tumors or granulomas, or
      even a degenerative process.

PMID- 15140726
TI  - Pli de passage fronto-parietal moyen of broca separates the motor homunculus.
AB  - The complete form of the pli de passage fronto-parietal moyen of Broca, a gyrus
      connecting the pre- and postcentral gyri at the level of the presumable primary
      motor (M1) hand area, represents a rare anatomic variation. By using functional
      MR imaging in a healthy subject incidentally found to harbor this configuration,
      we attempted to determine whether such an accessory gyrus would be functionally
      active and what effect it has on the complex somatotopic within-arm organization
      of M1. We found a specific and consistent activation pattern along the lateral
      and medial cortical boundaries of the pli de passage fronto-parietal moyen. The
      gyrus completely segregated the M1 finger from the M1 elbow representation, one
      being laterally and the other medially located. Furthermore the M1 wrist
      representation was consistently split by the pli de passage fronto-parietal moyen
      into a medial and lateral activation cluster. These findings demonstrate that
      this accessory gyrus not only contains functionally active neurons, but also
      leads to a functional separation of the motor homunculus at the level of the M1
      wrist representation. This is a remarkable finding, because the region of within
      arm representations in M1 was previously thought to be necessarily organized in a
      complex and intermingled fashion, without a topographic segregation between
      single body parts.

PMID- 15140727
TI  - Anatomically conformable, three-dimensional, detachable platinum microcoil system
      for the treatment of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: The configurations of detachable platinum coils have
      evolved over the last decade. Our objective was to assess the efficacy of the
      anatomically conformable three-dimensional (ACT) detachable platinum microcoil in
      the treatment of intracranial aneurysms. METHODS: A series of 141 patients
      presented between May 2000 and August 2002 to a single neurointerventionalist for
      endovascular treatment of intracranial aneurysms. Eight patients were treated at
      another institute or are now overseas. The remaining 133 patients had 141
      aneurysms, which were treated; 110 were ruptured and 31 were unruptured. The
      clinical conditions and aneurysm locations were recorded. The procedural
      technique was the same as that used with the Guglielmi detachable coil (GDC)
      device, though the coil detachment mechanism was unique. The ACT microcoil was
      used in almost all cases as the initial coil. RESULTS: Complete (100%) occlusion
      was achieved in 104 (74%) aneurysms. Thirty four (24%) had subtotal occlusion >
      or = 95%), and three (2%) had incomplete occlusion (<95%). The ACT coil conformed
      to both spherical and irregularly shaped aneurysms. No procedure-related deaths
      occurred, and there was no aneurysm rupture related to coil deployment. No
      postprocedural rebleeding was observed. CONCLUSION: The ACT microcoil device is
      feasible as an alternative platinum coil device, offering some advantages over
      other currently available devices.

PMID- 15140728
TI  - Preliminary experience with intra-arterial nicardipine as a treatment for
      cerebral vasospasm.
AB  - BACKGROUND AND PURPOSE: Papaverine is the primary intra-arterial (IA) treatment
      for vasospasm after aneurysmal subarachnoid hemorrhage (SAH); however, is it
      limited in effect and by adverse effects. We prospectively studied the use of IA
      nicardipine as a treatment for vasospasm. METHODS: Over 12 months, all patients
      with SAH who required interventional treatment for vasospasm were given IA
      nicardipine with or without angioplasty. Vasospasm was determined by serial
      clinical assessments and/or daily transcranial Doppler (TCD) imaging and
      confirmed by angiography. Doses of IA nicardipine per vessel were 0.5-6 mg. All
      patients were monitored for increased intracranial pressure (ICP) and change in
      cardiovascular or neurologic status. RESULTS: Forty-four vessels in 18 patients
      with vasospasm were treated with IA nicardipine alone. TCD data for 38 vessels
      (15 cases) were available. All vessels demonstrated immediate angiographic
      dilatation after IA nicardipine. No sustained cardiovascular changes were after
      treatment. ICP was transiently elevated in five patients and persistently
      elevated in one. Mean peak systolic velocities at TCD imaging were significantly
      reduced from pretreatment values in all treated vessels for 4 days after infusion
      (268.9 +/- 77.8 vs 197.6 +/- 74.1 cm/s, P <.001). Neurologic improvement after IA
      nicardipine occurred in eight (42.1%) patients. No clinical deterioration was
      noted. CONCLUSION: As shown by TCD imaging, IA nicardipine has an immediate and
      sustained effect on vasospasm. It does not appear to have sustained effect on ICP
      or cardiovascular status. This treatment warrants further study to determine its
      safety and efficacy.

PMID- 15140729
TI  - Carotid rupture during stent-assisted aneurysm treatment.
AB  - We report the case of a supraclinoid carotid rupture during the delivery of a
      balloon-expandable stent in a 59-year-old patient with incidental paraclinoid
      berry aneurysms for whom stent-assisted coiling was planned. The deployment of
      the stent resulted in immediate rupture of the artery. We describe the emergent
      management of this complication with prolonged balloon inflation to occlude the
      site of rupture, a treatment that led to the discharge of the patient 2 weeks
      later without any sequelae.

PMID- 15140730
TI  - Technical modification in the intracarotid chemotherapy and osmotic blood-brain
      barrier disruption procedure to prevent the relapse of carboplatin-induced
      orbital pseudotumor.
AB  - The blood-brain barrier disruption (BBBD) procedure is an established strategy to
      enhance drug delivery to brain tumors. Complication rates associated with this
      procedure are usually low, but when complications do occur, they usually mandate
      discontinuation of treatment. Orbital pseudotumor is an inflammatory condition of
      one or more extraocular muscles that produces limitation of ocular motility.
      Patients usually experience sudden diplopia associated with orbital pain,
      conjunctival chemosis and injection, and proptosis. Imaging of the orbit shows
      diffuse enlargement of the extraocular muscles, exophthalmia, and, rarely,
      sinusal or intracranial infiltration. On pathologic examinations, the soft
      tissues of the orbit are infiltrated with a mixture of eosinophils, lymphocytes,
      and plasma cells. Many etiologies can induce this syndrome, including the
      intracarotid infusion of platinum molecules. As part of a phase II study, a total
      of 110 patients were treated for malignant brain tumors with intra-arterial
      carboplatin, enhanced by the BBBD procedure, at the Sherbrooke University
      Hospital. Here we report on three patients who developed orbital pseudotumor
      ipsilateral to the carotid infused a few hours to days after the procedure. After
      the occurrence of this syndrome in the first patient, we developed a technical
      modification to the procedure that enabled uninterrupted treatment in the other
      two patients. This modification was as follows: after the mannitol infusion, and
      before carboplatin, the catheter was changed for a 3.5 tracker and was
      repositioned just above the emergence of the ophthalmic artery.

PMID- 15140731
TI  - Interventional MR imaging with an endospinal imaging coil: preliminary results
      with anatomic imaging of the canine and cadaver spinal cord.
AB  - Percutaneous intraspinal navigation (PIN) is a new minimally invasive approach to
      the subarachnoid space. Using conventional radiographic fluoroscopy, entrance is
      gained to the lumbar subarachnoid space, allowing navigation throughout the
      spinal canal. Using an antenna/guidewire introduced via PIN, we performed
      endospinal MR imaging of the thoracic spinal cord in a cadaver and canine
      subject. Comparison images were obtained with an optimal surface coil. PIN allows
      endospinal MR imaging of the spinal cord, providing significant signal-to-noise
      ratio gains over conventional imaging.

PMID- 15140732
TI  - Vertebroplasty versus kyphoplasty: a comparison and contrast.

PMID- 15140733
TI  - Spinal schwannoma with acute subarachnoid hemorrhage: a diagnostic challenge.
AB  - We report a case of spinal intradural schwannoma presenting with intracranial
      subarachnoid hemorrhage. Cerebral angiography studies were negative, but MR
      imaging of the spine revealed a large hemorrhagic tumor in the thoraco-lumbar
      junction. The tumor was misdiagnosed as ependymoma of the conus medullaris. This
      case illustrates the importance of a high index of suspicion for spinal disease
      in angiographically-negative subarachnoid hemorrhage and pitfalls in MR diagnosis
      of thoraco-lumbar tumors.

PMID- 15140734
TI  - MR imaging findings in delayed reversible myelopathy from lightning strike.
AB  - Delayed spinal cord injury following high-voltage electrical injury is a rare but
      well-documented phenomenon. The MR imaging features of this entity, however, have
      not been well documented. We report the MR imaging findings in a case of delayed
      sensory and motor deficits following a lightning strike. MR imaging revealed
      hyperintense signal within the cord on T2-weighted and STIR images extending from
      C1 to C3. Axial images localized the hyperintense signal to the posterolateral
      region of the spinal cord bilaterally. Follow-up MR imaging 6 weeks later
      demonstrated resolution of abnormal cord signal intensity.

PMID- 15140735
TI  - Cervical dural arteriovenous fistulae manifesting as subarachnoid hemorrhage:
      report of two cases and literature review.
AB  - Dural arteriovenous fistulas (DAVFs) in the craniocervical junction are rare but
      clinically important. DAVFs can be associated with subarachnoid hemorrhage (SAH),
      a feature distinguishing them from DAVFs in the thoracolumbar region. These
      lesions are often overlooked at cerebral angiography performed to assess SAH and
      account for a small proportion of angiographically negative SAHs. After managing
      two cases of cervical spinal DAVF manifesting as SAH, we analyzed all cases in
      the literature to identify features associated with bleeding at presentation.

PMID- 15140736
TI  - Swimmer's CT: improved imaging of the lower neck and thoracic inlet.
AB  - CT findings of the base of the neck are often degraded by beam-hardening artifact
      from the shoulder girdle. This artifact can be reduced by placing the patient in
      a "swimmer's" position, a supine position in which the patient has one arm fully
      abducted and the other arm lowered. We selectively employed swimmer's CT in
      patients between January 1999 and December 2002 when standard (arms-down) CT
      failed to depict suspected disease. In nine of 10 patients, swimmer's CT improved
      CT quality or accuracy or both over that obtained when the standard CT position
      was used.

PMID- 15140737
TI  - Head and neck paragangliomas: improved tumor detection using contrast-enhanced 3D
      time-of-flight MR angiography as compared with fat-suppressed MR imaging
      techniques.
AB  - BACKGROUND AND PURPOSE: MR imaging techniques have proved their efficacy in
      imaging the head and neck region. In this study, we compared T1-weighted, dual T2
      weighted, and fat-suppressed MR imaging and unenhanced and contrast-enhanced 3D
      time-of-flight MR angiography sequences for detection of head and neck
      paragangliomas. METHODS: Thirty-one patients with 70 paragangliomas were
      examined. Four combinations of MR images were reviewed by two neuroradiologists:
      T1-weighted and dual T2-weighted fast spin-echo images, T1- and T2-weighted fat
      suppressed fast spin-echo images, T1-weighted and contrast-enhanced T1-weighted
      fat-suppressed spin-echo images, and unenhanced and contrast-enhanced 3D time-of
      flight MR angiograms. The randomized examinations were independently evaluated
      for image quality, presence of tumor, tumor size, and intratumoral flow signal
      intensity. The standard of reference for presence of tumor was digital
      subtraction angiography. Data were analyzed by using the logistic regression
      method. RESULTS: Mean sensitivity, specificity, and negative predictive values,
      respectively, were assessed by the two observers to be as follows: for dual T2
      weighted fast spin-echo, 74%/99%/86%; for T2-weighted fat-suppressed fast spin
      echo, 70%/100%/85%; for contrast-enhanced T1-weighted fat-suppressed spin-echo,
      73%/100%/86%; and for unenhanced and contrast-enhanced 3D time-of-flight MR
      angiography, 89%/99%/93%. Sensitivity was significantly better for unenhanced and
      contrast-enhanced 3D time-of-flight MR angiography (P =.000028). More
      intratumoral flow signal intensity was depicted with unenhanced and contrast
      enhanced 3D time-of-flight MR angiography. CONCLUSION: A combination of
      unenhanced and contrast-enhanced 3D time-of-flight MR angiography is superior for
      detecting paragangliomas and should be added to a standard imaging protocol,
      especially for patients with familial paragangliomas because they are more
      susceptible to multicentric disease.

PMID- 15140738
TI  - Transoral penetration of a half-split chopstick between the basion and the dens.
AB  - A 6-year-old girl was admitted for transoral penetrating injury by a half-split
      chopstick. Subsequent CT imaging examinations showed that the chopstick had
      passed between the basion and the dens and reached the subarachnoid space just at
      the medulla oblongata. A sagittal reconstructed CT scan was useful for the
      evaluation of the injury. Imaging findings and their clinical relevance are
      discussed.

PMID- 15140739
TI  - Spontaneous sphenoid sinus mucocele revealed by meningitis and brain abscess in a
      12-year-old child.
AB  - Sphenoid sinus mucocele is an uncommon lesion related to inflammatory disease
      that is diagnosed after surgery or a traumatic event. This report describes an
      unusual case revealed by bacterial meningitis and cerebral abscess in a 12-year
      old child. CT and MR imaging allowed precise extension to the skull base in
      preoperative management and follow-up investigations. Endoscopic transnasal
      marsupialisation of the mucocele and antibiotic therapy led to complete
      remission. There was no evidence of recurrence after 6 months, which suggests
      that sphenoid mucoceles, regardless of size and complications, can be treated by
      endoscopic sinus surgery.

PMID- 15140740
TI  - Massive calcium pyrophosphate dihydrate crystal deposition disease: a cause of
      pain of the temporomandibular joint.
AB  - Calcium pyrophosphate dihydrate deposition (CPDD) disease is a disorder that
      occasionally affects the temporomandibular joint (TMJ) and temporal bone, causing
      pain (66.6% of cases), swelling (50%), trismus (36.8%), and hearing loss (22.2%).
      Diagnosis of CPDD is challenging because clinical symptoms and imaging features
      are not characteristic and may mimic a chondrosarcoma. When the diagnosis of CPDD
      of the TMJ is under consideration, conventional radiographs of the wrist or the
      knee may contribute to the final diagnosis. Imaging features of CPDD are
      discussed with a review of the literature.

PMID- 15140742
TI  - Subacute sclerosing panencephalitis findings at MR imaging, diffusion MR imaging,
      and proton MR spectroscopy.
AB  - A case of subacute sclerosing panencephalitis in a 2-year-old boy is reported. In
      addition to asymmetric lesions in the parietotemporal lobes, right thalamus, and
      globus pallidus, symmetric patterns were notable in the brain stem, middle
      cerebellar pedincles, and dentate nuclei. Proton MR spectroscopy revealed
      markedly decreased N-acetylaspartate peaks and normal choline and myo-inositol
      levels in the lesions. Diffusion MR imaging revealed an elevated diffusion
      pattern manifested with high apparent diffusion coefficient values (1.14-1.60 x
      10(-3) mm(2)/s) compared with those in normal-appearing brain tissue (0.65-1.00 x
      10(-3) mm(2)/s) and subtle high signal intensity characteristics on diffusion
      weighted images obtained at b = 1000 s/mm(2).

PMID- 15140741
TI  - MR imaging presentation of intracranial disease associated with Langerhans cell
      histiocytosis.
AB  - BACKGROUND AND PURPOSE: Intracranial manifestations of Langerhans cell
      histiocytosis (LCH) are underestimated in frequency and diversity. We categorized
      the spectrum of MR imaging changes in LCH. METHODS: We retrospectively reviewed
      474 MR images in 163 patients with LCH and 55 control subjects. Lesions were
      characterized by anatomic region and signal intensity. Brain atrophy was
      assessed. RESULTS: We noted osseous lesions in the craniofacial or skull bones in
      56% of patients, meningeal lesions in 29%, and choroid-plexus involvement in 6%.
      In the hypothalamic-pituitary region, infundibular thickening occurred in 50%;
      pronounced hypothalamic mass lesions in 10%; and infundibular atrophy in 29%. The
      pineal gland had a cystic appearance in 28%, and pineal-gland enlargement (>10
      mm) was noted in 14%. Nonspecific paranasal-sinus or mastoid opacifications were
      seen in 55% of patients versus 20% of controls, and accentuated Virchow-Robin
      spaces occurred in 70% of patients versus 27% of controls (P <.001). Intra-axial,
      white-matter parenchymal changes resulted in a leukoencephalopathy-like pattern
      in 36%. Enhancing lesions in a vascular distribution were noted in 5%. Gray
      matter changes suggestive of neurodegeneration were identified in the cerebellar
      dentate nucleus in 40% and in the supratentorial basal ganglia in 26%. All
      patients with neurodegenerative lesions had lesions in the extra-axial spaces.
      Cerebral atrophy was found in 8%. CONCLUSION: In LCH, cranial and intracranial
      changes at MR imaging include 1) lesions of the craniofacial bone and skull base
      with or without soft-tissue extension; 2) intracranial, extra-axial changes
      (hypothalamic-pituitary region, meninges, circumventricular organs); 3)
      intracranial, intra-axial changes (white matter and gray matter); and 4) cerebral
      atrophy.

PMID- 15140743
TI  - Neurologically normal complete asymmetric lumbar spine duplication.
AB  - Spine duplication, which is at the severe end of the split cord malformation, is
      rarely seen. Radiographic, CT, and MR images of a 15-year-old girl who had lower
      back pain showed asymmetric lumbar spine duplication with spinal cord tethering
      secondary to a filum lipoma in the sacrum. Despite gross spinal abnormalities,
      the patient was neurologically intact and has been followed up with conservative
      treatment.

PMID- 15140744
TI  - Assessment of the neuroradiology fellowship match: year 3.
AB  - BACKGROUND AND PURPOSE: When the fellowship match for trainees entering
      neuroradiology programs was first proposed in 2001, the program directors in
      neuroradiology agreed to a 3-year trial utilizing the National Residency Match
      Program (NRMP) for selecting fellows. A decision as to whether to continue with
      the neuroradiology fellowship match was to be assessed at the 3-year mark in
      2004. METHODS: A Web survey designed through the offices of the ASNR was
      distributed to neuroradiology fellowship program directors after the results of
      the most recent fellowship match were tabulated in June 2003. The questionnaire
      included items about the current sentiment about the fellowship selection
      process. RESULTS: Most (52 of 61 = 85%) neuroradiology program directors favored
      continuing the match system for selecting fellows. Most believed that the match
      1) had little impact on their success in recruiting fellows (43 of 62 = 69%), 2)
      was fairly administered (100%), and 3) was appropriately timed from February to
      June in the third year of residency (56 of 65 = 86%). The number of candidates
      entering the neuroradiology match increased from 71 in 2001 to 124 in 2003.
      CONCLUSION: Support for continuing a match system for selecting fellows remains
      high (85%) among neuroradiology program directors. The system is considered fair
      and does not harm many programs. The recruitment of fellows to neuroradiology via
      the match has increased over the 3 years of its existence.

PMID- 15140745
TI  - Structural domains involved in substrate selectivity in two neutral amino acid
      transporters.
AB  - The ability of the two highly homologous Na(+)/Cl(-)-dependent neutral amino acid
      transporters KAAT1 and CAATCH1, cloned from the midgut epithelium of the larva
      Manduca sexta, to transport different amino acids depends on the cotransported
      ion, on pH, and on the membrane voltage. Different organic substrates give rise
      to transport-associated currents with their own characteristics, which are
      notably distinct between the two proteins. Differences in amplitude, kinetics,
      and voltage dependence of the transport-associated currents have been observed,
      as well as different substrate selectivity patterns measured by radioactive amino
      acid uptake assays. These diversities represent useful tools to investigate the
      structural determinants involved in the substrate selectivity. To identify these
      regions, we built four chimeric proteins between the two transporters. These
      proteins, heterologously expressed in Xenopus laevis oocytes, were analyzed by
      two-electrode voltage clamp and uptake measurements. Initially, we exchanged the
      first three domains, obtaining the chimeras C3K9 and K3C9 (where numbers indicate
      the transmembrane domains and letters represent the original proteins), which
      showed electrophysiological and [(3)H]amino acid uptake characteristics
      resembling those of KAAT1 and CAATCH1, respectively. Subsequent substitution of
      the last four domains in C3K9 and K3C9 gave the proteins C3K5C4 and K3C5K4, which
      showed the same behavior as KAAT1 and CAATCH1 in electrophysiological and
      transport determinations. These results suggest that in KAAT1 and CAATCH1, only
      the central transmembrane domains (from 4 to 8) of the protein are responsible
      for substrate selectivity.

PMID- 15140746
TI  - Isoform switching from SM-B to SM-A myosin results in decreased contractility and
      altered expression of thin filament regulatory proteins.
AB  - We previously generated an isoform-specific gene knockout mouse in which SM-B
      myosin is permanently replaced by SM-A myosin. In this study, we examined the
      effects of SM-B myosin loss on the contractile properties of vascular smooth
      muscle, specifically peripheral mesenteric vessels and aorta. The absence of SM-B
      myosin leads to decreased velocity of shortening and increased isometric force
      generation in mesenteric vessels. Surprisingly, the same changes occur in aorta,
      which contains little or no SM-B myosin in wild-type animals. Calponin and
      activated mitogen-activated protein kinase expression is increased and caldesmon
      expression is decreased in aorta, as well as in bladder. Light chain-17b isoform
      (LC(17b)) expression is increased in aorta. These results suggest that the
      presence or absence of SM-B myosin is a critical determinant of smooth muscle
      contraction and that its loss leads to additional changes in thin filament
      regulatory proteins.

PMID- 15140747
TI  - Overexpression of human KCNA5 increases IK V and enhances apoptosis.
AB  - Apoptotic cell shrinkage, an early hallmark of apoptosis, is regulated by K+
      efflux and K+ channel activity. Inhibited apoptosis and downregulated K+ channels
      in pulmonary artery smooth muscle cells (PASMC) have been implicated in
      development of pulmonary vascular medial hypertrophy and pulmonary hypertension.
      The objective of this study was to test the hypothesis that overexpression of
      KCNA5, which encodes a delayed-rectifier voltage-gated K+ (Kv) channel, increases
      K+ currents and enhances apoptosis. Transient transfection of KCNA5 caused 25- to
      34-fold increase in KCNA5 channel protein level and 24- to 29-fold increase in Kv
      channel current (I(K(V))) at +60 mV in COS-7 and rat PASMC, respectively. In
      KCNA5-transfected COS-7 cells, staurosporine (ST)-mediated increases in caspase-3
      activity and the percentage of cells undergoing apoptosis were both enhanced,
      whereas basal apoptosis (without ST stimulation) was unchanged compared with
      cells transfected with an empty vector. In rat PASMC, however, transfection of
      KCNA5 alone caused marked increase in basal apoptosis, in addition to enhancing
      ST-mediated apoptosis. Furthermore, ST-induced apoptotic cell shrinkage was
      significantly accelerated in COS-7 cells and rat PASMC transfected with KCNA5,
      and blockade of KCNA5 channels with 4-aminopyridine (4-AP) reduced K+ currents
      through KCNA5 channels and inhibited ST-induced apoptosis in KCNA5-transfected
      COS-7 cells. Overexpression of the human KCNA5 gene increases K+ currents (i.e.,
      K+ efflux or loss), accelerates apoptotic volume decrease (AVD), increases
      caspase-3 activity, and induces apoptosis. Induction of apoptosis in PASMC by
      KCNA5 gene transfer may serve as an important strategy for preventing the
      progression of pulmonary vascular wall thickening and for treating patients with
      idiopathic pulmonary arterial hypertension (IPAH).

PMID- 15140749
TI  - Modeling action potential generation and propagation in NRK fibroblasts.
AB  - Normal rat kidney (NRK) fibroblasts change their excitability properties through
      the various stages of cell proliferation. The present mathematical model has been
      developed to explain excitability of quiescent (serum deprived) NRK cells. It
      includes as cell membrane components, on the basis of patch-clamp experiments, an
      inwardly rectifying potassium conductance (G(Kir)), an L-type calcium conductance
      (G(CaL)), a leak conductance (G(leak)), an intracellular calcium-activated
      chloride conductance [G(Cl(Ca))], and a gap junctional conductance (G(gj)),
      coupling neighboring cells in a hexagonal pattern. This membrane model has been
      extended with simple intracellular calcium dynamics resulting from calcium entry
      via G(CaL) channels, intracellular buffering, and calcium extrusion. It
      reproduces excitability of single NRK cells and cell clusters and intercellular
      action potential (AP) propagation in NRK cell monolayers. Excitation can be
      evoked by electrical stimulation, external potassium-induced depolarization, or
      hormone-induced intracellular calcium release. Analysis shows the roles of the
      various ion channels in the ultralong ( approximately 30 s) NRK cell AP and
      reveals the particular role of intracellular calcium dynamics in this AP. We
      support our earlier conclusion that AP generation and propagation may act as a
      rapid mechanism for the propagation of intracellular calcium waves, thus
      contributing to fast intercellular calcium signaling. The present model serves as
      a starting point to further analyze excitability changes during contact
      inhibition and cell transformation.

PMID- 15140748
TI  - Growth factors induce monocyte binding to vascular smooth muscle cells:
      implications for monocyte retention in atherosclerosis.
AB  - Adhesive interactions between monocytes and vascular smooth muscle cells (VSMC)
      may contribute to subendothelial monocyte-macrophage retention in
      atherosclerosis. We investigated the effects of angiotensin II (ANG II) and
      platelet-derived growth factor (PDGF)-BB on VSMC-monocyte interactions. Treatment
      of human aortic VSMC (HVSMC) with ANG II or PDGF-BB significantly increased
      binding to human monocytic THP-1 cells and to peripheral blood monocytes. This
      was inhibited by antibodies to monocyte beta(1)- and beta(2)-integrins. The
      binding was also attenuated by blocking VSMC arachidonic acid (AA) metabolism by
      inhibitors of 12/15-lipoxygenase (12/15-LO) or cyclooxygenase-2 (COX-2).
      Conversely, binding was enhanced by overexpression of 12/15-LO or COX-2. Direct
      treatment of HVSMC with AA or its metabolites also increased binding.
      Furthermore, VSMC derived from 12/15-LO knockout mice displayed reduced binding
      to mouse monocytic cells relative to genetic control mice. Using specific signal
      transduction inhibitors, we demonstrated the involvement of Src, phosphoinositide
      3-kinase, and MAPKs in ANG II- or PDGF-BB-induced binding. Interestingly, after
      coculture with HVSMC, THP-1 cell surface expression of the scavenger receptor
      CD36 was increased. These results show for the first time that growth factors may
      play additional roles in atherosclerosis by increasing monocyte binding to VSMC
      via AA metabolism and key signaling pathways. This can lead to monocyte
      subendothelial retention, CD36 expression, and foam cell formation.

PMID- 15140750
TI  - Dibasic phosphorylation sites in the R domain of CFTR have stimulatory and
      inhibitory effects on channel activation.
AB  - To better understand the mechanisms by which PKA-dependent phosphorylation
      regulates CFTR channel activity, we have assayed open probabilities (P(o)), mean
      open time, and mean closed time for a series of CFTR constructs with mutations at
      PKA phosphorylation sites in the regulatory (R) domain. Forskolin-stimulated
      channel activity was recorded in cell-attached and inside-out excised patches
      from transiently transfected Chinese hamster ovary cells. Wild-type CFTR and
      constructs with a single Ser-to-Ala mutation as well as octa (Ser-to-Ala
      mutations at 8 sites) and constructs with one or two Ala-to-Ser mutations were
      studied. In cell-attached patches, Ser-to-Ala mutations at amino acids 700, 795,
      and 813 decreased P(o), whereas Ser-to-Ala mutations at 737 and 768 increased
      P(o). In general, differences in P(o) were due to differences in mean closed
      time. For selected constructs with either high or low values of P(o), channel
      activity was measured in excised patches. With 1 mM ATP, P(o) was similar to that
      observed in cell-attached patches, but with 10 mM ATP, all constructs tested
      showed elevated P(o) values. ATP-dependent increases in P(o) were due to
      reductions in mean closed time. These results indicate that R-domain
      phosphorylation affects ATP binding and not the subsequent steps of hydrolysis
      and channel opening. A model was developed whereby R-domain phosphorylation, in a
      site-dependent manner, alters equilibrium between forms of CFTR with low and high
      affinities for ATP.

PMID- 15140751
TI  - Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular
      nonpigmented ciliary epithelium.
AB  - The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain
      natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) display
      hypotensive effects in the mammalian eye by lowering the intraocular pressure
      (IOP), a function that is mediated by the bilayer ocular ciliary epithelium (CE),
      in conjunction with the trabecular meshwork. ANP regulates Na(+)/H(+) exchanger
      (NHE) activity, and inhibitors of NHE have been shown to lower IOP. We examined
      whether NPs influence the NHE activity of the CE, which is comprised of pigmented
      (PE) and nonpigmented (NPE) epithelial cells, by directly recording the rate of
      intracellular pH (pH(i)) recovery from its inner NPE cell layer. NPs inhibited,
      in a dose-dependent manner (1-100 nM), the rate of pH(i) recovery with the order
      of potency CNP > ANP > BNP, indicative that this inhibition is mediated by the
      presence of NPR type B receptors. 8-Bromo-cGMP (8-BrcGMP), a nonhydrolyzable
      analog of cGMP, mimicked NPs in inhibiting the rate of Na(+)-dependent pH(i)
      recovery. In contrast, ethylisopropyl amiloride (EIPA, 100 nM) or amiloride (10
      microM) completely abolished the pH(i) recovery by NHE. 18alpha-Glycyrrhetinic
      acid (18alpha-GA), a gap junction blocker, attenuated the inhibitory effect of
      CNP on the rate of pH(i) recovery, suggesting that NHE activity in both cell
      layers of the CE is coregulated. This interpretation was supported, in part, by
      the coexpression of NHE-1 isoform mRNA in both NPE and PE cells. The mechanism by
      which the inhibitory effect of NPs on NHE-1 activity might influence the net
      solute movement or fluid transport by the bilayer CE remains to be determined.

PMID- 15140752
TI  - Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment
      epithelial cell line ARPE-19.
AB  - Hypoxia-induced physiological stress plays a central role in various neovascular
      diseases of the eye. Increased expression of hypoxia-inducible factor 1alpha (HIF
      1alpha) and subsequent formation of HIF-1 dimers active at the vascular
      endothelial growth factor (VEGF) promoter lead to expression of this potent
      angiogenic factor in the retina, including retinal pigment epithelial (RPE)
      cells. We previously demonstrated that insulin-like growth factor I (IGF-I)
      stimulates VEGF and IGF binding protein (IGFBP)-3 secretion in RPE cells. In this
      study we examined IGF-I-induced HIF-1alpha expression, VEGF and IGFBP-3
      secretion, and the autocrine actions of VEGF and IGFBP-3 on these processes in
      the spontaneously transformed RPE cell line ARPE-19. Cells were treated with
      CoCl(2), IGF-I, recombinant human (rh)IGFBP-3, and rhVEGF. Immunoblot analysis
      revealed IGF-I-induced upregulation of total HIF-1alpha protein, whereas
      luciferase reporter assays of HIF-1 transcriptional activity demonstrated
      accumulation of HIF-1alpha correlated with the formation of functional HIF-1
      heterodimers. Western and ligand blot analyses of RPE cell conditioned medium
      confirmed that IGF-I stimulated VEGF and IGFBP-3 secretion. rhVEGF stimulated
      IGFBP-3 secretion in an IGF-I- and HIF-1alpha-independent manner, whereas rhIGFBP
      3 attenuated IGF-I-induced VEGF secretion. These findings demonstrate the
      multifaceted autocrine regulation of IGF-I-induced VEGF secretion by IGFBP-3
      secreted in response to both IGF-I and, to a lesser extent, VEGF. These results
      provide evidence for HIF-1-dependent and -independent mechanisms by which IGF-I
      regulates VEGF and IGFBP-3 secretion.

PMID- 15140753
TI  - Proteomic research: potential opportunities for clinical and physiological
      investigators.
AB  - Proteomics is the comprehensive and systematic study of proteins, which are
      functional molecules. Although proteins are products of gene expression, there
      are more proteins than genes due to the posttranslational modifications of
      proteins, making the study of proteins difficult. Protein expression is tissue
      specific, and its function is modulated by variety of factors, including other
      proteins, phosphates, sulfates, carbohydrates, and lipids, as well as other
      metabolites. Because of the dynamic nature of protein expression and
      posttranslational modifications, identification and quantification of proteins
      alone are not sufficient to understand functional changes. Emerging technologies
      will allow investigators to perform a combination of metabolic labeling and
      identification as well as quantification and measurement of the synthesis rates
      of a large number of proteins in a tissue. This offers the opportunity to better
      understand the regulation of tissue functions. Rapid advances in mass
      spectrometry, protein purification techniques, isotope labeling of proteins, and
      bioinformatics are likely to improve our understanding of physiological states
      and altered functions in diseased states. Such mechanistic information will
      improve the ability to perform early diagnosis of tumors and other diseases and
      develop prognostic indexes and novel therapies.

PMID- 15140754
TI  - Glucagon-like peptide 1 agonists and the development and growth of pancreatic
      beta-cells.
AB  - Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone
      that stimulates glucose-dependent insulin production and secretion from
      pancreatic beta-cells. Other recognized actions of GLP-1 are to suppress glucagon
      secretion and hepatic glucose output, delay gastric emptying, reduce food intake,
      and promote glucose disposal in peripheral tissues. All of these actions are
      potentially beneficial for the treatment of type 2 diabetes mellitus. Several GLP
      1 agonists are in clinical trials for the treatment of diabetes. More recently,
      GLP-1 agonists have been shown to stimulate the growth and differentiation of
      pancreatic beta-cells, as well as to exert cytoprotective, antiapoptotic effects
      on beta-cells. Recent evidence indicates that GLP-1 agonists act on receptors on
      pancreas-derived stem/progenitor cells to prompt their differentiation into beta
      cells. These new findings suggest an approach to create beta-cells in vitro by
      expanding stem/progenitor cells and then to convert them into beta-cells by
      treatment with GLP-1. Thus GLP-1 may be a means by which to create beta-cells ex
      vivo for transplantation into patients with insulinopenic type 1 diabetes and
      severe forms of type 2 diabetes.

PMID- 15140755
TI  - Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes.
AB  - Glucagon-like peptide 1 (GLP-1) is a product of proglucagon that is secreted by
      specialized intestinal endocrine cells after meals. GLP-1 is insulinotropic and
      plays a role in the incretin effect, the augmented insulin response observed when
      glucose is absorbed through the gut. GLP-1 also appears to regulate a number of
      processes that reduce fluctuations in blood glucose, such as gastric emptying,
      glucagon secretion, food intake, and possibly glucose production and glucose
      uptake. These effects, in addition to the stimulation of insulin secretion,
      suggest a broad role for GLP-1 as a mediator of postprandial glucose homeostasis.
      Consistent with this role, the most prominent effect of experimental blockade of
      GLP-1 signaling is an increase in blood glucose. Recent data also suggest that
      GLP-1 is involved in the regulation of beta-cell mass. Whereas other
      insulinotropic gastrointestinal hormones are relatively ineffective in
      stimulating insulin secretion in persons with type 2 diabetes, GLP-1 retains this
      action and is very effective in lowering blood glucose levels in these patients.
      There are currently a number of products in development that utilize the GLP-1
      signaling system as a mechanism for the treatment of diabetes. These compounds,
      GLP-1 receptor agonists and agents that retard the metabolism of native GLP-1,
      have shown promising results in clinical trials. The application of GLP-1 to
      clinical use fulfills a long-standing interest in adapting endogenous
      insulinotropic hormones to the treatment of diabetes.

PMID- 15140756
TI  - Parathyroid responsiveness to hypocalcemic and hypercalcemic stimuli in adult
      growth hormone deficiency after growth hormone replacement.
AB  - Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Previous
      reports have suggested that alterations in parathyroid gland responsiveness to
      changes in calcium concentration may play a role in the genesis of osteoporosis
      in untreated AGHD patients. We investigated the endogenous parathyroid hormone
      [PTH-(1-84)] response to hypocalcemic and hypercalcemic stimuli induced by sodium
      EDTA and calcium gluconate infusion, respectively, and to PTH-(1-34) infusion in
      AGHD patients before and during GH replacement (GHR). We have demonstrated that
      the maximum PTH-(1-84) stimulation and suppression occurred at significantly
      higher calcium concentrations and in response to smaller changes in calcium
      concentrations after GHR. The calcemic response to the effects of PTH-(1-34)
      infusion significantly increased after GHR. The calcium set point (the calcium
      concentration at which the rate of PTH secretion is one-half of its maximal
      value) significantly increased in all groups after 3 mo on GHR, and it increased
      further at 12 mo. Our results suggest increased parathyroid gland sensitivity to
      smaller changes in serum calcium and increased end-organ sensitivity to the
      effects of PTH in AGHD patients after GHR. These findings may help us to
      understand the mechanisms underlying the genesis of osteoporosis in AGHD
      patients.

PMID- 15140758
TI  - High concentration of glucose inhibits glomerular endothelial eNOS through a PKC
      mechanism.
AB  - Kidney glomeruli are important targets of diabetic nephropathy. We hypothesized a
      high concentration of glucose could suppress glomerular endothelial nitric oxide
      synthase (eNOS) by a protein kinase C (PKC) mechanism, as has been found in other
      tissues. Mouse kidney slices (150-200 microm) were bathed in Hanks' solution with
      100 microM L-arginine and exposed to either 5 or 20-30 mM D-glucose.
      Immunofluorescence identified only eNOS in normal mouse glomeruli. Measurements
      of glomerular NO concentration with NO-sensitive fluorescent dye (4,5
      diaminofluorescein diacetate) using confocal microscopy and NO-sensitive
      microelectrodes verified that resting glomeruli had active production of NO that
      was inhibited by N(G)-nitro-L-arginine methyl ester. High-concentration (20-30
      mM) D-glucose inhibited 60-70% of the NO production within 15-30 min; L-glucose
      at the same concentration did not have any effect. Inhibition of PKC-beta with
      100 nM ruboxistaurin prevented eNOS suppression in high-glucose media. Activation
      of PKC with 100 nM phorbol ester also suppressed the glomerular NO concentration.
      We concluded that eNOS in the renal glomerular capillary endothelial cells is
      suppressed by activity of PKC at high-glucose concentrations comparable to those
      in diabetic animals and humans. The consequence is a rapid decline in the
      generation of NO in the glomerular endothelial cells in the presence of a high
      concentration of glucose.

PMID- 15140759
TI  - Regulation of an inwardly rectifying K+ channel by nitric oxide in cultured human
      proximal tubule cells.
AB  - We investigated the effects of nitric oxide (NO) on activity of the inwardly
      rectifying K(+) channel in cultured human proximal tubule cells, using the cell
      attached mode of the patch-clamp technique. An inhibitor of NO synthases,
      N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM), reduced channel
      activity, which was restored by an NO donor, sodium nitroprusside (SNP; 10
      microM) or 8-bromo-cGMP (8-BrcGMP; 100 microM). However, SNP failed to activate
      the channel in the presence of an inhibitor of soluble guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM). Similarly, the SNP effect
      was abolished by a protein kinase G (PKG)-specific inhibitor, KT-5823 (1 microM),
      but not by a protein kinase A-specific inhibitor, KT-5720 (500 nM). Another NO
      donor, S-nitroso-N-acetyl-D,L-penicillamine (10 microM), mimicked the SNP-induced
      channel activation. In contrast to the stimulatory effect of SNP at a low dose
      (10 microM), a higher dose of SNP (1 mM) reduced channel activity, which was not
      restored by 8-BrcGMP. Recordings of membrane potential with the slow whole cell
      configuration demonstrated that l-NAME (100 microM) and the high dose of SNP (1
      mM) depolarized the cell by 10.1 +/- 2.6 and 9.2 +/- 1.0 mV, respectively,
      whereas the low dose of SNP (10 microM) hyperpolarized it by 7.1 +/- 0.7 mV.
      These results suggested that the endogenous NO would contribute to the
      maintenance of basal activity of this K(+) channel and hence the potential
      formation via a cGMP/PKG-dependent mechanism, whereas a high dose of NO impaired
      channel activity independent of cGMP/PKG-mediated processes.

PMID- 15140757
TI  - Different mechanisms can alter fatty acid transport when muscle contractile
      activity is chronically altered.
AB  - We examined whether skeletal muscle transport rates of long-chain fatty acids
      (LCFAs) were altered when muscle activity was eliminated (denervation) or
      increased (chronic stimulation). After 7 days of chronically stimulating the
      hindlimb muscles of female Sprague-Dawley rats, the LCFA transporter proteins
      fatty acid translocase (FAT)/CD36 (+43%) and plasma membrane-associated fatty
      acid-binding protein (FABPpm; +30%) were increased (P < 0.05), which resulted in
      the increased plasmalemmal content of these proteins (FAT/CD36, +42%; FABPpm
      +13%, P < 0.05) and a concomitant increase in the LCFA transport rate into giant
      sarcolemmal vesicles (+44%, P < 0.05). Although the total muscle contents of
      FAT/CD36 and FABPpm were not altered (P > 0.05) after 7 days of denervation, the
      LCFA transport rate was markedly decreased (-39%). This was associated with
      reductions in plasmalemmal FAT/CD36 (-24%) and FABPpm (-28%; P < 0.05). These
      data suggest that these LCFA transporters were resequestered to their
      intracellular depot(s) within the muscle. Combining the results from these
      experiments indicated that changes in rates of LCFA transport were correlated
      with concomitant changes in plasmalemmal FAT/CD36 and FABPpm, but not necessarily
      with their total muscle content. Thus chronic alterations in muscle activity can
      alter the rates of LCFA transport via different mechanisms, either 1) by
      increasing the total muscle content of FAT/CD36 and FABPpm, resulting in a
      concomitant increase at the sarcolemma, or 2) by reducing the plasma membrane
      content of these proteins in the absence of any changes in their total muscle
      content.

PMID- 15140760
TI  - The urinary proteome in Fanconi syndrome implies specificity in the reabsorption
      of proteins by renal proximal tubule cells.
AB  - Polypeptides present in the glomerular filtrate are almost completely reabsorbed
      in the first segment of the proximal tubule by receptor-mediated endocytosis; in
      renal Fanconi syndrome (FS), there is failure to reabsorb many of these
      polypeptides. We have compared the urinary proteomes in patients with Dent's
      disease (due to a CLC5 mutation), a form of FS, with normal subjects using three
      different proteomic methods. No differences in the levels of several plasma
      proteins were detected when standardized to total protein amounts. In contrast,
      several vitamin and prosthetic group carrier proteins were found in higher
      amounts in Dent's urine (with respect to total protein). Similarly, complement
      components, apolipoproteins, and some cytokines represented a larger proportion
      of the Dent's urinary proteome, suggesting that such proteins are reabsorbed more
      efficiently than other classes of proteins. Conversely, proteins of renal origin
      were found in proportionately higher amounts in normal urine. Thus the uptake of
      filtered vitamins, which are normally bound to their respective carrier proteins
      to prevent urinary losses, seems a key function of the proximal tubule; in
      addition, this nephron segment may also play a critical role in reabsorbing
      potentially cytotoxic polypeptides of plasma origin, preventing them from acting
      at more distal nephron sites.

PMID- 15140761
TI  - CD40-induced transcriptional activation of vascular endothelial growth factor
      involves a 68-bp region of the promoter containing a CpG island.
AB  - Vascular endothelial growth factor (VEGF) is produced by several cell types in
      the kidney, and its expression is tightly regulated for the maintenance of normal
      renal physiology. Increases or decreases in its expression are associated with
      proteinuria and renal disease. Recently, we found that the expression of VEGF is
      markedly induced following interactions between CD40 ligand (CD40L) and CD40.
      Here, endothelial cells (EC) or Jurkat T cell lines were transiently transfected
      with luciferase reporter constructs under the control of the human VEGF promoter
      and were treated with human soluble CD40L (sCD40L). We identified a CD40
      responsive 68-bp region (bp -50 to +18) of the promoter and 43 bp within this
      region (bp -25 to +18) that have 97% homology to a sequence of CpG dinucleotides.
      A computerized search revealed that the CpG region has putative binding domains
      for the transcriptional repressor protein methyl CpG binding protein-2 (MeCP2).
      In EMSA, we found that the 43-bp methylated sequence formed four complex(es) with
      nuclear extracts from untreated EC and reduced binding of at least one complex
      when nuclear lysates from sCD40L-activated EC (30 min) were used. Supershift
      analysis using anti-MeCP2 demonstrated that most of the complex(es) in both
      untreated and sCD40L-activated EC involved interactions between the 43-bp DNA and
      MeCP2. In addition, we found that other CpG binding proteins may also interact
      with this region of the promoter. Taken together, this is the first demonstration
      that CpG binding transcriptional repressor proteins including MeCP2 may be of
      importance in VEGF biology.

PMID- 15140762
TI  - AVP-induced VIT32 gene expression in collecting duct cells occurs via trans
      activation of a CRE in the 5'-flanking region of the VIT32 gene.
AB  - VIT32, a vasopressin-induced transcript, inhibits Na(+) transport when
      coexpressed with the epithelial sodium channel in Xenopus laevis oocytes (EMBO J
      21: 5109-5117, 2002). To understand the mechanism of VIT32 gene regulation, we
      examined the effect of DDAVP and cAMP stimulation on VIT32 expression in M-1
      mouse collecting duct cells and in H441 human airway epithelial cells. Elevation
      of cAMP with forskolin and IBMX increased VIT32 gene expression with a peak
      effect at 2 h. The increase in gene expression was abolished by H89 and by
      actinomycin D, suggesting that cAMP stimulates VIT32 mRNA expression by a PKA
      mediated increase in gene transcription. An approximately 1.5-kb fragment of the
      5'-flanking region of VIT32 was cloned and was able to confer cAMP-stimulated
      reporter gene activity when transfected into M-1 and H441 cells. By deletion
      analysis and site-directed mutagenesis, a cAMP response element (CRE) was
      identified within the proximal promoter region that was sufficient to account for
      the increase in VIT32 gene expression seen with DDAVP and elevation of cAMP.
      Furthermore, DDAVP-stimulated VIT32 promoter-reporter activity was inhibited by
      H89 and by a dominant negative CREB construct. Finally, we were able to identify
      CREB as a nuclear protein that bound to the VIT32 CRE in gel mobility shift
      assays. In summary, DDAVP stimulates transcription of VIT32 via a CRE within the
      proximal promoter region of the VIT32 gene.

PMID- 15140764
TI  - Developmental expression and biological activity of gastrin-releasing peptide and
      its receptors in the kidney.
AB  - Mammalian gastrin-releasing peptide (GRP) has a widespread distribution and
      multiple stimulating effects on metabolism, release of regulatory peptides,
      gastrointestinal and pancreatic secretions, and behavior. GRP is a potent mitogen
      for a number of tumor types, including colon and lung. Although GRP is known to
      stimulate the growth of renal tumors, little is known of its synthesis,
      distribution, and receptors in the developing and mature kidney. Both Northern
      blot analysis and RT-PCR revealed the presence of GRP mRNA in ovine kidney from
      midgestation through to adulthood. GRP mRNA was detected in rat kidney from
      embryonic day 19 to postnatal day 30 by RT-PCR. Sequence-specific
      radioimmunoassay demonstrated the presence of substantial amounts of fully
      processed amidated GRP in the ovine renal cortex and medulla. The mRNA for the
      major receptor subtype, GRP-R, was present in fetal and adult sheep and rat
      kidneys. The mRNA for the low-affinity GRP receptor, bombesin receptor subtype-3
      (BRS-3), was only detected in the rat kidney. In the ovine kidney,
      immunohistochemistry localized GRP predominantly to the thick ascending limb of
      the loop of Henle. mRNAs for GRP, GRP-R, and BRS-3 were detected in the human
      embryonic kidney cell line HEK293, and radioimmunoassay of cell extracts and
      conditioned media revealed the presence of proGRP but not the amidated form.
      However, amidated GRP did stimulate the proliferation of these cells. These
      studies demonstrate that the developing and mature kidney may be previously
      unidentified sites of autocrine or paracrine action for GRP.

PMID- 15140763
TI  - A naturally occurring human Nedd4-2 variant displays impaired ENaC regulation in
      Xenopus laevis oocytes.
AB  - The epithelial Na(+) channel (ENaC) is regulated by the ubiquitin-protein ligase
      Nedd4-2 via interaction with ENaC PY-motifs. These PY-motifs are mutated/deleted
      in Liddle's syndrome, resulting in elevated Na(+) reabsorption and hypertension
      explained partly by impaired ENaC-Nedd4-2 interaction. We hypothesized that Nedd4
      2 is a susceptibility gene for hypertension and screened 856 renal patients and
      healthy controls for mutations in a subset of exons of the human Nedd4-2 gene
      that are relevant for ENaC regulation by PCR/single-strand conformational
      polymorphism. Several variants were identified, and one nonsynonymous mutation
      (Nedd4-2-P355L) was further characterized. This mutation next to the 3' donor
      site of exon 15 does not affect in vitro splicing of Nedd4-2 mRNA. However, in
      the Xenopus oocyte expression system, Nedd4-2-P355L-dependent ENaC inhibition was
      weaker compared with the wild type (Nedd4-2-WT), and this difference depended on
      the presence of intact PY-motifs on ENaC. This could not be explained by the
      amount of wild type or mutant Nedd4-2 coimmunoprecipitating with ENaC. When the
      phosphorylation level of human Nedd4-2 Ser(448) (known to be phosphorylated by
      the Sgk1 kinase) was determined with a specific anti-pSer(448) antibody, we
      observed stronger basal phosphorylation of Nedd4-2-P355L. Both the
      phosphorylation level and the accompanying amiloride-sensitive Na(+) currents
      could be further enhanced to approximately the same levels by coexpressing Sgk1.
      In addition, the role of the two other putative Sgk1 phosphorylation sites (S342
      and T367) appears also to be affected by the P355L mutation. The differential
      phosphorylation status between wild-type and mutant Nedd4-2 provides an
      explanation for the different potential to inhibit ENaC activity.

PMID- 15140765
TI  - Central nervous system involvement in Sjogren's syndrome.

PMID- 15140766
TI  - Influence of hip dysplasia on the development of osteoarthritis of the hip.
AB  - BACKGROUND: It has been suggested that in some patients with primary hip
      osteoarthritis (OA), the disease occurs as a consequence of acetabular dysplasia
      or hip dysplasia (HD). OBJECTIVE: To carry out a systematic review to investigate
      the association between acetabular dysplasia and hip OA. METHODS: A database
      search of Medline, Embase, and the Cochrane library was carried out, and articles
      that aimed at studying the relationship between HD and hip OA were identified.
      The methodological quality of the selected studies was assessed using a
      standardised set of criteria, and a best evidence synthesis was used to summarise
      the results from the individual studies. RESULTS: Five cohort studies and four
      case-control studies were included in this review. One cohort study had the
      correct design to answer the question and was considered to be a high quality
      study. This study reported a positive association between HD and hip OA. Overall,
      limited evidence was found for a positive association between HD and hip OA. Most
      studies included older people. In younger age groups the relation between HD and
      OA or hip complaints may be much higher. CONCLUSION: The evidence for the
      influence of HD on the occurrence of hip OA, at age 50-60 or older, is limited.

PMID- 15140767
TI  - Appropriate and effective management of rheumatoid arthritis.
AB  - Early referral (at <3 months) and early DMARD treatment enable the course of RA
      to be changed. Once the disease has become aggressive it is much harder to treat
      and improvements will not be as great as they would have been with earlier
      treatment. The latest strategies and treatments enable remission to be achieved
      in many more patients than formerly.

PMID- 15140768
TI  - Intervertebral discitis presenting as oligoarthritis.

PMID- 15140769
TI  - Galectin-3 surface expression on human adult chondrocytes: a potential substrate
      for collagenase-3.
AB  - BACKGROUND: Galectin-3 is a lectin detected in mature and early hypertrophic
      chondrocytes; osteoarthritic (OA) chondrocytes can re-express hypertrophic
      markers. OBJECTIVE: To investigate the synthesis and subcellular localisation of
      galectin-3 in adult chondrocytes as well as the possibility of cleavage of
      galectin-3 by collagenase-1 and -3. METHODS: Galectin-3 was assessed by
      immunohistochemistry and real time polymerase chain reaction (PCR) in normal and
      OA cartilage. Its localisation was investigated by subcellular fractionation,
      immunocytology, and flow cytometry. Proteolysis of galectin-3 by collagenase-1
      and -3 was determined by in vitro assay. RESULTS: Galectin-3 expression was
      increased 2.4-fold as measured by reverse transcriptase (RT)-PCR (p<0.05, n = 5)
      and threefold by immunohistochemistry (p<0.003 n = 6) in OA cartilage compared
      with normal cartilage. In adult chondrocytes, galectin-3 was found in the cytosol
      and membrane enriched fractions. Both immunocytology and flow cytometry confirmed
      the presence of galectin-3 at the surface of chondrocytes. A strong correlation
      was found between integrin-beta1 and galectin-3 expression at the surface of
      chondrocytes. Moreover, collagenase-3 cleaved galectin-3 with a higher activity
      than collagenase-1. The proteolysed sites generated were identical to those
      produced by gelatinases A and B. CONCLUSION: Galectin-3 may play a part in OA,
      having two roles, one intracellular and not yet identified, and another at the
      cell surface, possibly related to the interaction of chondrocytes and the
      cartilage matrix.

PMID- 15140770
TI  - Doppler ultrasound findings in healthy wrists and finger joints.
AB  - OBJECTIVE: To evaluate the presence of flow by Doppler ultrasound (DUS) in the
      wrist and finger joints (carpometacarpal 1 (CMC1), metacarpophalangeal (MCP), and
      proximal interphalangeal (PIP) joints) of healthy controls. METHODS: Twenty seven
      healthy volunteers (15 women, 12 men; mean age 45 years, range 18-93) with a
      total of 324 joints were examined by DUS. The synovial vascularisation was
      determined by colour Doppler and the spectral Doppler resistive index (RI).
      Patients were only included if no synovitis was suspected at the clinical
      examination and the values for biochemical analysis were within the normal range.
      RESULTS: We found colour pixels in 15 of the 27 examined wrist scans and in 8 of
      these a measurable RI. In the CMC1 joint, colour pixels were found in 11 of the
      27 scans and in 9 of these a measurable RI. For the MCP joints, colour pixels
      were found in 10 out of 135 scans and in 3 of these a measurable RI. The mean RI
      for all three types of joints was 0.85 and the mean pixel fraction varied from
      0.05 to 0.08. Only one PIP joint scan was found to have colour pixels and a flow
      with an RI of 0.67. CONCLUSION: Synovial vascularisation may be detected in
      healthy subjects using DUS. Newer US machines have higher Doppler sensitivity,
      and it is necessary to be able to distinguish normal from pathological synovial
      flow.

PMID- 15140771
TI  - Up regulation of cathepsin K expression in articular chondrocytes in a transgenic
      mouse model for osteoarthritis.
AB  - OBJECTIVES: To study the expression of cysteine proteinases, particularly
      cathepsin K, and their extracellular inhibitor cystatin C in articular cartilage
      of transgenic Del1 mice which harbour a short deletion mutation in a type II
      collagen transgene and are predisposed to early onset osteoarthritis. METHODS:
      Northern analysis was used to measure mRNA levels of cathepsins B, H, K, L, and
      S, and cystatin C in total RNA extracted from knee joints of Del1 mice, using
      their non-transgenic litter mates as controls. Immunohistochemistry and
      morphometry was used to study the distribution of cathepsin K and cystatin C in
      the knee joints. RESULTS: Up regulation of cathepsin K mRNA expression was seen
      in the knee joints of transgenic Del1 mice at the onset of cartilage
      degeneration. Cathepsin K was found near sites of matrix destruction in articular
      chondrocytes, particularly in clusters of proliferating cells, and in calcified
      cartilaginous matrix. In intact articular cartilage of control animals, cathepsin
      K was only seen in a small number of chondrocytes. Upon aging, control animals
      also developed osteoarthritis, which was accompanied by increased cathepsin K
      expression. Cystatin C was mostly localised in and around chondrocytes located in
      calcified cartilage, with no obvious association with the onset of cartilage
      degeneration. CONCLUSION: The temporospatial distribution of cathepsin K in
      osteoarthritic cartilage suggests a role for this enzyme in the pathogenesis of
      osteoarthritis. Because cathepsin K can digest cartilage matrix components it may
      contribute to the development of osteoarthritic lesions. These data may provide
      new clues for the development of treatments aimed at preventing cartilage
      degeneration.

PMID- 15140773
TI  - Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis.
AB  - OBJECTIVE: To assess basal function and responsiveness of the hypothalamic
      pituitary-adrenal (HPA) axis in patients with ankylosing spondylitis during
      dynamic testing. METHODS: Insulin induced hypoglycaemia (IIH) (Actrapid HM 0.1
      IU/kg, as intravenous bolus) was induced in 17 patients and 11 healthy controls
      matched for age, sex, and body mass index. Concentrations of glucose,
      adrenocorticotrophic hormone (ACTH), cortisol, insulin, dehydroepiandrosterone
      sulphate (DHEAS), 17alpha-hydroxyprogesterone, interleukin 6 (IL-6), and tumour
      necrosis factor alpha (TNFalpha) were determined in plasma. RESULTS: Comparable
      basal cortisol levels were found in the two groups, with a trend to be lower in
      ankylosing spondylitis. In the ankylosing spondylitis group, there were higher
      concentrations of IL-6 (mean (SEM): 16.6 (2.8) pg/ml v 1.41 (0.66) pg/ml in
      controls; p<0.001) and TNFalpha (8.5 (1.74) pg/ml v 4.08 (0.42) pg/ml in
      controls; p<0.01). Glucose, insulin, ACTH, DHEAS, and 17alpha-hydroxyprogesterone
      did not differ significantly from control. The IIH test was carried out
      successfully in 11 of the 17 patients with ankylosing spondylitis, and the ACTH
      and cortisol responses were comparable with control. General linear modelling
      showed a different course of glycaemia (p = 0.041) in the ankylosing spondylitis
      patients who met the criteria for a successful IIH test compared with the
      controls. CONCLUSIONS: The results suggest there is no difference in basal HPA
      axis activity and completely preserved responsiveness of the HPA axis in patients
      with ankylosing spondylitis. The interpretation of the different course of
      glycaemia during IIH in ankylosing spondylitis requires further investigation.

PMID- 15140772
TI  - Adenovirus mediated intra-articular expression of collagenase-3 (MMP-13) induces
      inflammatory arthritis in mice.
AB  - OBJECTIVES: To better understand the role of collagenase-3 (MMP-13) in joint
      inflammation by investigating the consequences of transient overexpression of
      human collagenase-3 (matrix metalloproteinase-13 (MMP-13)), introduced by
      adenoviral gene delivery, in the mouse knee joint. METHODS: A single dose
      (5x10(7) pfu) of recombinant adenovirus coding either for beta-galactosidase
      (RAdLacZ) or human MMP-13 (RAdMMP-13) was injected intra-articularly into the
      knee joint of adult mice. The joints were analysed at frequent intervals up to 4
      weeks by histology, immunohistochemistry, and RNA analysis. RESULTS: When RAdLacZ
      reporter virus was used, adenoviruses efficiently infected synovial cells,
      chondrocytes of articular cartilage, and hypertrophic chondrocytes of the growth
      plate. The infection was transient as no reporter gene activity was detected 3
      weeks after the injection. After RAdMMP-13 injection into the knee joints,
      expression of human MMP-13 in joint tissues resulted in an arthritis
      characterised by recruitment of inflammatory cells and increased production of
      cytokines and chemokines, synovial hyperplasia, and pannus formation. After the
      loss of MMP-13 transgene expression at 3 weeks, these inflammatory changes began
      to diminish. CONCLUSIONS: MMP-13 has a role in the onset of inflammatory reaction
      in synovium. However, damage to articular cartilage was only rarely detected
      after the short term overexpression of MMP-13.

PMID- 15140774
TI  - Prognostic factors for remission in early rheumatoid arthritis: a multiparameter
      prospective study.
AB  - OBJECTIVE: To determine prognostic factors for remission in early rheumatoid
      arthritis. METHODS: 191 patients with rheumatoid arthritis whose disease duration
      was less than one year were followed up prospectively for five years. Remission,
      defined by a disease activity score (DAS) of <1.6, was used as the outcome
      measure. Baseline clinical, laboratory, genetic, and radiographic data (with
      radiographic scores determined by Sharp's method, modified by van der Heijde)
      were obtained. RESULTS: 48 patients (25.1%) fulfilled the remission criteria at
      the three year follow up visit, and 30 (15.7%) at three and five years. On
      univariate analysis by Fisher's exact test, remission at three years and
      persistent remission at five years were closely correlated with baseline DAS
      values, C reactive protein level, Ritchie score, health assessment questionnaire
      score, duration of morning stiffness, and to a lesser extent baseline total
      radiological scores and rheumatoid factor negativity. No significant correlation
      was found with sex, age, extra-articular manifestations, erythrocyte
      sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin
      antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or
      HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline
      independent variables predictive of remission were low DAS, Ritchie score,
      morning stiffness duration, and total radiographic score. CONCLUSIONS: Baseline
      prognostic factors for remission in early rheumatoid arthritis were mainly
      clinical markers of disease activity and radiological scores.

PMID- 15140775
TI  - Cytokine and chemokine receptor profile of peripheral blood mononuclear cells
      during treatment with infliximab in patients with active rheumatoid arthritis.
AB  - OBJECTIVES: To analyse immunological changes during treatment with a monoclonal
      anti-tumour necrosis factor alpha (TNFalpha) antibody, infliximab, in patients
      with rheumatoid arthritis (RA). METHODS: 25 patients with RA and 5 patients with
      other arthritides were studied during the first 6 weeks of treatment with
      infliximab. At the start of treatment and after 2 and 6 weeks, spontaneous
      expression of CCR3 and CCR5 on peripheral blood T cells and monocytes was studied
      by flow cytometry. The secretion and mRNA expression of interferon gamma
      (IFNgamma), interleukin (IL)4, IL5, and TNFalpha from phytohaemagglutinin (PHA)
      stimulated peripheral blood mononuclear cells was measured with an ELISA and RT
      PCR. Plasma levels of C reactive protein, serum amyloid protein A, rheumatoid
      factor, and antibodies to filaggrin and citrullinated cyclic peptide were
      measured with an ELISA. RESULTS: The number of CD4 T cells and CD14 monocytes
      expressing CCR3 (p = 0.013, p = 0.009, respectively) and CD8 T cells expressing
      CCR5 (p = 0.040) as well as PHA stimulated secretion of IL4 and IFNgamma (p<0.05)
      increased during treatment in patients with RA. 15 (60%) patients with RA
      achieved clinical response (at least ACR20) during the first 2 weeks. The number
      of T cells expressing CCR3 and CCR5 was higher before treatment in non-responders
      than in responders (p<0.05). The number of T cells increased in responders.
      CONCLUSION: Increase in secretion of Th1 and Th2 cytokines together with induced
      expression of chemokine receptors on T cells and monocytes suggest restoration of
      peripheral cell mediated immunity and blockade of the accumulation of
      inflammatory cells in joints as response to treatment.

PMID- 15140776
TI  - A randomised placebo controlled 12 week trial of budesonide and prednisolone in
      rheumatoid arthritis.
AB  - OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal
      systemic exposure, with conventional glucocorticoid treatment and placebo in
      rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over
      12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3
      mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo.
      Particular attention was paid to the pattern of clinical response and to changes
      in the four week period following discontinuation of treatment. RESULTS: There
      were improvements in tender joint count and swollen joint count on budesonide 9
      mg compared with placebo (28% for tender and 34% for swollen joint counts,
      p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less
      effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on
      budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid
      and significant reduction in symptoms and signs in response to budesonide 9 mg
      and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks.
      There was no evidence that budesonide provided a different pattern of symptom
      control from prednisolone, or that symptoms became worse than placebo treatment
      levels after discontinuation of glucocorticoid treatment. Adverse effects
      attributable to glucocorticoids were equally common in all groups. CONCLUSIONS:
      The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved
      within a short time of initiating treatment, are maintained for three months, and
      are not associated with any rebound in symptoms after stopping treatment.

PMID- 15140778
TI  - Management of osteoarthritis (OA) with an unsupervised home based exercise
      programme and/or patient administered assessment tools. A cluster randomised
      controlled trial with a 2x2 factorial design.
AB  - BACKGROUND: Diary recording of pain and disabling activities in osteoarthritis
      (OA) is widely recommended, but, to our knowledge, its impact on symptoms has not
      been investigated. Exercise programmes have been shown to be effective when
      patients are closely supervised by nurses or physiotherapists; however, data are
      lacking on the efficacy of an unsupervised home based exercise regimen in
      patients with OA. OBJECTIVES: To evaluate the clinical efficacy of patient
      administered assessment tools and an unsupervised home based exercise programme
      alone or in combination in patients with OA. METHODS: The study was a 24 week,
      open cluster randomised controlled trial with a factorial design. Rheumatologists
      (n = 867) were assigned to four groups according to the treatment given:
      standardised tools (ST; n = 220), exercises (EX; n = 213), both tools and
      exercises (ST+EX; n = 213), or usual care (n = 221). Each rheumatologist was to
      enroll four patients who met the American College of Rheumatology criteria for OA
      (three with knee OA, one with hip OA). "Tools" consisted of weekly recording of
      pain and disabling activities in a diary. A home based exercise programme was
      performed daily at least four times per week with the aid of videotape and
      booklet. In addition to exercise and assessment, all patients received 12.5 mg or
      25 mg of the non-steroidal anti-inflammatory drug rofecoxib once daily. Outcome
      variables were: pain (measured on a visual analogue scale, 0-100); Western
      Ontario and McMaster Universities Osteoarthritis Index, function subscale (0
      100); and patient assessment of the quality of care (0-100). RESULTS: Overall,
      2957 patients with OA (2216 knee, 741 hip) were included. After 24 weeks, both
      pain and function improved in the ST, EX, ST+EX, and usual care groups (mean (SD)
      -17 (27), -20 (29), -15 (27), -19 (29); and -11 (19), -12 (19), -10 (19), -11
      (20), respectively), without significant differences between groups. However,
      patients in the EX and ST+EX groups were more likely to agree that their
      rheumatologist had done his best to preserve their functional and physical
      activities. CONCLUSION: Although patients' assessments favoured the exercise
      programme, results from this study failed to demonstrate a short term symptomatic
      effect of the two non-pharmacological treatments (weekly recording of condition
      and exercise) in patients with OA concurrently receiving nonsteroidal anti
      inflammatory drugs.

PMID- 15140777
TI  - High production of proinflammatory and Th1 cytokines by dendritic cells from
      patients with rheumatoid arthritis, and down regulation upon FcgammaR triggering.
AB  - OBJECTIVE: To assess whether DC from RA produce altered cytokine levels and
      whether this is regulated by triggering of Fc gamma receptors (FcgammaR).
      METHODS: The production of proinflammatory (TNFalpha, IL1, IL6), Th1 (IL12,
      IFNgamma), and Th2 (IL10) cytokine profiles of immature DC (iDC) from patients
      with RA and healthy subjects upon triggering of FcgammaR dependent and
      independent pathways was investigated. iDC, derived from blood monocytes by
      standardised protocols, were stimulated with immune complexes (IC) at day 6 for
      48 hours and, subsequently, for 2 days with LPS in the presence or absence of IC
      or IFNgamma, resulting in fully matured DC (mDC). IL1, IL6, TNFalpha, IFNgamma,
      IL12, and IL10 levels in supernatants were measured by ELISA and RIA. RESULTS:
      mDC from patients with RA showed a markedly increased production of IL1, IL6,
      TNFalpha, and IL10 compared with DC from healthy donors. Triggering of FcgammaR
      decreased the production of proinflammatory cytokines IL1, IL12, and IFNgamma by
      iDC and mDC in RA and controls. The production of IL6 and TNFalpha decreased in
      patients with RA, whereas it was increased in controls. Triggering of FcgammaR
      independent mechanisms using IFNgamma increased the production of proinflammatory
      and Th1 cytokines, which was more pronounced in RA. CONCLUSION: FcgammaR
      dependent pathways influence cytokine production by DC. A skewed balance towards
      proinflammatory and Th1 cytokines in RA can, at least partly, be restored by
      triggering FcgammaR on DC in RA. Insight into the mechanism which determines the
      FcgammaR balance might lead to new strategies to abrogate Th1 driven inflammatory
      processes in RA.

PMID- 15140779
TI  - Detecting structural changes in early experimental osteoarthritis of tibial
      cartilage by microscopic magnetic resonance imaging and polarised light
      microscopy.
AB  - OBJECTIVES: To detect changes in the collagen fibril network in articular
      cartilage in a canine experimental model of early osteoarthritis (OA) using
      microscopic magnetic resonance imaging (microMRI) and polarised light microscopy
      (PLM). METHODS: Eighteen specimens from three pairs of the medial tibia of an
      anterior cruciate ligament transection canine model were subjected to microMRI
      and PLM study 12 weeks after surgery. For each specimen, the following
      experiments were carried out: (a) two dimensional microMRI images of T(2)
      relaxation at four orientations; (b) the tangent Young's modulus; and (c) two
      dimensional PLM images of optical retardance and fibril angle. Disease induced
      changes in tissue were examined across the depth of the cartilage at a microMRI
      resolution of 13.7-23.1 microm. RESULTS: Several distinct changes from T(2)
      weighted images of cartilage in OA tibia were seen. For the specimens that were
      covered at least in part by the meniscus, the significant changes in microMRI
      included a clear shift in the depth of maximum T(2) (21-36%), a decrease in the
      superficial zone thickness (37-38%), and an increase in cartilage total thickness
      (15-27%). These microMRI changes varied topographically in the tibia surface
      because they were not significant in completely exposed locations in medial
      tibia. The microMRI results were confirmed by the PLM measurements and correlated
      well with the mechanical measurements. CONCLUSION: Both microMRI and PLM can
      detect quantitatively changes in collagen fibre architecture in early OA and
      resolve topographical variations in cartilage microstructure of canine tibia.

PMID- 15140780
TI  - A randomised placebo controlled trial of delipidated, deglycolipidated
      Mycobacterium vaccae as immunotherapy for psoriatic arthritis.
AB  - OBJECTIVES: To test the hypothesis that PVAC, delipidated, deglycolipidated heat
      killed Mycobacterium vaccae, is an effective and safe treatment for psoriatic
      arthritis (PsA). This treatment has shown promising results in psoriasis.
      METHODS: 36 patients with PsA in two centres were studied in this double blind,
      placebo controlled, randomised trial. Patients were randomised to receive two
      intradermal injections of 50 micro g PVAC or placebo and were followed up for 24
      weeks. The primary end point was the Psoriatic Arthritis Response Criteria
      (PsARC), a composite measure based on changes in joint tenderness and swelling
      scores and physician and patient global assessments. RESULTS: The PsARC response
      at either 12 or 24 weeks was achieved by 9/18 (50%) placebo and 9/18 (50%) PVAC
      patients (p = 1.0). No significant differences in the Psoriasis Activity and
      Severity Index (PASI), patient or physician global assessments, CRP, or Health
      Assessment Questionnaire score over time were found between the two groups.
      However, changes in the pain visual analogue scale over time did differ between
      the two groups (p = 0.006): at 24 weeks the mean score in the PVAC group had
      declined by 19.2 mm and in the placebo group had increased by 4.8 mm. PVAC was
      well tolerated with no increased incidence of adverse events compared with
      placebo. CONCLUSIONS: PVAC was not shown to be as effective as immunotherapy for
      PsA. The striking response to placebo in this study reinforces the importance of
      adequately controlling therapeutic trials in PsA.

PMID- 15140781
TI  - Health related quality of life in multiple musculoskeletal diseases: SF-36 and EQ
      5D in the DMC3 study.
AB  - OBJECTIVE: To examine the health related quality of life of persons with one or
      more self reported musculoskeletal diseases, as measured by the short form 36
      item health status survey (SF-36) and the Euroqol questionnaire (EQ-5D). METHODS:
      A sample of Dutch inhabitants aged 25 years or more (n = 3664) participated in a
      questionnaire survey. Twelve lay descriptions of common musculoskeletal diseases
      were presented and the subjects were asked whether they had ever been told by a
      physician that they had any of these. Their responses were used to assess the
      prevalence of these conditions. Commonly used scores of SF-36 and descriptive
      scores from EQ-5D are presented, along with standardised differences between
      disease groups and the general population. RESULTS:  SUBJECTS: with
      musculoskeletal diseases had significantly lower scores on all SF-36 dimensions
      than those without musculoskeletal disease, especially for physical functioning
      (SF-36 score (SE), 75.2 (0.5) v 87.8 (0.5)); role limitations caused by physical
      problems (67.1 (0.9) v 85.8 (0.8)); and bodily pain (68.5 (0.5) v 84.1 (0.5)).
      The worst health related quality of life patterns were found for osteoarthritis
      of the hip, osteoporosis, rheumatoid arthritis, and fibromyalgia. Those with
      multiple musculoskeletal diseases had the poorest health related quality of life.
      Similar results were found for EQ-5D. CONCLUSIONS: All musculoskeletal diseases
      involve pain and reduced physical function. The coexistence of musculoskeletal
      diseases should be taken into account in research and clinical practice because
      of its high prevalence and its substantial impact on health related quality of
      life.

PMID- 15140783
TI  - Long term evaluation of radiographic disease progression in a subset of patients
      with rheumatoid arthritis treated with leflunomide beyond 2 years.
AB  - OBJECTIVES: To assess the effect of long term (>2 years) leflunomide treatment on
      radiographic progression in patients with RA. METHODS: Patients treated with
      leflunomide for >2 years in one of three phase III trials and subsequent
      extensions, for whom paired, evaluable radiographs at baseline and study end
      point were available, were included. Radiographs of hands and feet were assessed
      according to the modified Sharp/van der Heijde scoring method, for erosion, joint
      space narrowing, and total score. Changes from baseline were assessed, and a
      predicted yearly progression rate estimated for each patient. RESULTS: 128 of the
      original 824 patients were included, with mean disease duration 5.1 years and
      mean leflunomide treatment duration 4.3 years until the final x ray examination.
      The mean change from baseline in total score was 8.6 with yearly adjusted rate
      1.9, and the median change was 2 with yearly adjusted rate 0.5, compared with 7.9
      and 4.9, respectively, before leflunomide treatment. After treatment, the rate
      improved in 92/128 (72%) patients and deteriorated in 21/128 (16%). In 42 (33%)
      patients who had a total score >0 at baseline, no radiographic progression
      occurred after leflunomide treatment. CONCLUSIONS: In a subset of patients who
      continued treatment long term, leflunomide treatment reduced the rate of
      radiographic damage.

PMID- 15140784
TI  - Grey scale and power Doppler sonographic changes induced by intra-articular
      steroid injection treatment.
AB  - OBJECTIVE: To investigate the ability of high resolution grey scale sonography
      (GSS) and power Doppler sonography (PDS) to assess short term soft tissue changes
      induced by intra-articular steroid injection in the small joints of patients with
      chronic synovitis. METHODS: 20 patients with clinically active synovitis of a
      small joint unresponsive to systemic drug treatment underwent a sonographic
      guided intralesional injection with triamcinolone acetonide. Clinical
      examinations were carried out by a trained rheumatologist. GSS and PDS
      examinations were performed independently by two examiners unaware of the results
      of the clinical examination. Joint cavity widening and power Doppler signal were
      evaluated and graded on a semiquantitative scale ranging from 1 to 4. Clinical
      and sonographic follow up examinations were carried out 2 weeks after the
      injection with triamcinolone acetonide. RESULTS: All intra-articular injections
      were successfully carried out and documented under sonographic guidance. In 19/20
      patients, baseline sonographic examinations clearly detected morphological and
      perfusional signs of synovitis. At follow up examinations, clinical and
      sonographic scores had improved significantly. CONCLUSION: GSS and PDS appear to
      be a useful adjunctive tool for assessing short term soft tissue changes induced
      by intra-articular injection treatment with triamcinolone acetonide in small
      joints of patients with chronic arthritis.

PMID- 15140785
TI  - Successful treatment of genital ulcers with infliximab in Behcet's disease.

PMID- 15140786
TI  - Lupus myocarditis in children.

PMID- 15140782
TI  - Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies.
AB  - OBJECTIVE: To analyse the clinical and laboratory features of patients with
      thrombotic microangiopathic haemolytic anaemia (TMHA) associated with
      antiphospholipid antibodies (aPL). METHODS: A computer assisted (PubMed) search
      of the literature was performed to identify all cases of TMHA associated with aPL
      from 1983 to December 2002. RESULTS: 46 patients (36 female) with a mean (SD) age
      at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%)
      patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical
      manifestation of APS in 26 (57%) patients. The clinical presentations were
      haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure
      (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%),
      and HELLP (haemolysis, elevated liver enzymes, and low platelet count in
      association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in
      86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in
      89%. Steroids were the most common treatment (69% of episodes), followed by
      plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%),
      immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in
      only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes
      treated with PE. Death occurred in 10/46 (22%) patients. CONCLUSIONS: The results
      emphasise the need for systematic screening for aPL in all patients with clinical
      and laboratory features of TMHA. The existence of TMHA in association with an APS
      forces one to rule out the presence of the catastrophic variant of this syndrome.
      PE is indicated as a first line of treatment for all patients with TMHA
      associated with aPL.

PMID- 15140787
TI  - Dose escalation of leflunomide (LEF) to 40 mg once daily in patients with
      rheumatoid arthritis and insufficient response to standard dose LEF.

PMID- 15140788
TI  - Polyclonal immunoglobulins for intravenous use induce interleukin 10 release in
      vivo and in vitro.

PMID- 15140789
TI  - Cevimeline gargle for the treatment of xerostomia in patients with Sjogren's
      syndrome.

PMID- 15140790
TI  - Systemic inflammation in osteoarthritis.

PMID- 15140791
TI  - Infliximab efficiency and failure.

PMID- 15140792
TI  - Ultrasound detection of knee patellar enthesitis.

PMID- 15140793
TI  - Progesterone injection and egg production in turkey hens.
AB  - An arrest in laying associated with either a polyovarian follicle (POF) or a
      polycystic ovarian follicle (PCOF) syndrome has been reported in turkey hens
      photostimulated at an early age with a constant-light photoperiod. Hens
      expressing the POF or PCOF syndrome had stopped laying for several weeks, but the
      ovary contained an increased number of mature-size and larger follicles (POF
      hens), which were cystic (PCOF) in some of the hens. Hens with the POF or PCOF
      syndrome had plasma progesterone (P(4)) concentrations that were relatively high
      and without surges. We hypothesized that high plasma P(4) concentrations may
      block ovulatory surges of LH but not the growth or maintenance of hierarchical
      follicles leading to development of the POF or PCOF syndrome in turkey hens. In
      the first six studies, hens were photostimulated with either a 14L:10D or a
      24L:0D photoperiod and, after laying for 1-38 wk, were then injected daily for up
      to 14 days with P(4) (up to 1.50 mg kg(-1) day(-1)) and necropsied. At all ages,
      the oviposition rate was reduced at a P(4) dosage of 0.17 mg kg(-1) day(-1). With
      dosages of 0.33 mg kg(-1) day(-1) or greater, however, ovipositions stopped in
      most hens within approximately 2 days. For hens laying for less than 15 wk,
      oviductal weight and number of hierarchical follicles of P(4)-injected hens were
      not different from control vehicle-injected hens, but the numbers of mature,
      cystic, and atretic follicles were increased. For hens laying for 38 wk, when
      treated with P(4), oviductal weight and number of hierarchical follicles
      decreased, but number of atretic follicles increased. No effect of photoperiod
      was found on egg production, oviductal weight, or follicle number, and none of
      the hens developed POF or PCOF syndrome in these experiments. Two additional
      experiments were conducted with hens early in the reproductive period that had
      been photostimulated with 14L:10D or 24L:0D and injected with P(4) (0.33 mg kg(
      1) day(-1)) for 10 or 12 days but not necropsied until 3 wk after the last
      injection. Most of the hens photostimulated with the 24L:0D photoperiod and
      injected with P(4), and a few of the hens photostimulated with the 14L:10D
      photoperiod and injected with P(4), had developed the PCOF syndrome when
      necropsied. The hens with the PCOF syndrome had high levels of P(4) when
      necropsied. From these studies, we concluded that the PCOF syndrome can be
      induced early in the reproduction period by photostimulating turkey hens with a
      24L: 0D photoperiod, injecting them for 10 to 12 days with P(4) at a dosage of
      0.33 mg kg(-1) day(-1), and then waiting 3 wk for the PCOF syndrome to develop.

PMID- 15140794
TI  - Human cytomegalovirus-induced upregulation of intercellular cell adhesion
      molecule-1 on villous syncytiotrophoblasts.
AB  - Human cytomegalovirus (HCMV) is secreted apically from villous trophoblasts, thus
      congenital infection is not likely to occur by basal release across the basement
      membrane. As an alternative route, we hypothesize that an HCMV-infected villous
      syncytiotrophoblast (ST) upregulates intercellular adhesion molecule (ICAM)-1,
      causing blood monocytes to bind to the ST and induce apoptosis. Purified
      (>99.99%) populations of human villous trophoblasts were differentiated into an
      ST-like culture, infected with HCMV strain AD169, and assessed for ICAM-1
      expression by immunofluorescence. Infection strongly upregulated ICAM-1 24 h
      after challenge. ICAM-1 was also stimulated by transfection with viral genes IE2
      55, IE1-72, and IE2-86, but not by UV-inactivated virus. Infection with a green
      fluorescent protein recombinant virus allowed infection and ICAM-1 expression to
      be topographically located. We found that ICAM-1 was expressed on both infected
      and noninfected cells. Furthermore, antibody to tumor necrosis factor (TNF)alpha
      and, to a lesser extent, interleukin (IL)1 beta inhibited ICAM-1 upregulation on
      noninfected cells but not on infected cells. We conclude that HCMV IE proteins
      stimulate ICAM-1 expression on villous trophoblasts by paracrine release of TNF
      alpha and IL1 beta, as well as by a direct effect on infected cells.

PMID- 15140795
TI  - Expression and functional significance of mouse paraspeckle protein 1 on
      spermatogenesis.
AB  - Paraspeckle protein 1 (PSP1) in humans is a recently identified component protein
      of a novel nuclear body, paraspeckle. The protein has a DBHS (Drosophila
      behavior, human splicing) motif that is found in PSF and p54(nrb)/NonO proteins.
      These DBHS-containing proteins have been reported to be involved in various
      nuclear events such as DNA replication, transcription, and mRNA processing. Here
      we show that mouse paraspeckle protein 1 (mPSP1; encoded by the Pspc1 gene) has
      two isoforms with different C-termini lengths. Abundant expression of the longer
      isoform (mPSP1-alpha) and the shorter one (mPSP1-beta) were observed in testis
      and kidney, respectively. Transiently expressed mPSP1-alpha was localized in
      nuclei, but mPSP1-beta was localized in both nuclei and cytoplasm. These
      observations suggest that alternative splicing regulates tissue distribution and
      subcellular localization. Like other DBHS-containing proteins, mPSP1 has RNA
      binding activity. In mouse testis, mPSP1-alpha was found in the nuclear matrix
      fraction. Furthermore, by coimmunoprecipitation, we confirmed that mPSP1
      interacts with other DBHS-containing proteins, PSF and p54(nrb)/NonO. Therefore,
      we conclude that mPSP1 may regulate multiple phases of important nuclear events
      during spermatogenesis.

PMID- 15140796
TI  - Centrally applied somatostatin inhibits the estrogen-induced luteinizing hormone
      surge via hypothalamic gonadotropin-releasing hormone cell activation in female
      rats.
AB  - Overexpression of growth hormone (GH) as well as GH-deficiency dramatically
      impairs reproductive function. Decreased reproductive function as a result of
      altered GH release is, at least partially, due to changes at the hypothalamic
      pituitary level. We hypothesize that hypothalamic somatostatin (SOM), the
      inhibiting factor of GH release from the pituitary, may play a central role in
      the "crosstalk" between the somatotropic and gonadotropic axes. In the present
      study we investigated the possible effects of a centrally applied SOM analog on
      the LH surge and the concurrent activation of hypothalamic GnRH neurons in female
      rats. To this end, female rats were treated with estradiol 2 wk after ovariectomy
      and were given a single central injection with either the SOM analog, octreotide,
      or saline just prior to surge onset, after which hourly blood samples were taken
      to measure LH. Two weeks later, the experimental setup was randomly repeated to
      collect brains during the anticipated ascending phase of the LH surge. Vibratome
      sections were subsequently double-stained for GnRH and cFos peptide. Following
      octreotide treatment, LH surges were significantly attenuated compared to those
      in saline-treated control females. Also, octreotide treatment significantly
      decreased the activation of hypothalamic GnRH neurons. These results clearly
      demonstrate that SOM is able to inhibit LH release, at least in part by
      decreasing the activation of GnRH neurons. Based on these results, we hypothesize
      that hypothalamic SOM may be critically involved in the physiological regulation
      of the proestrus LH surge.

PMID- 15140797
TI  - Ontogeny of a demethylation domain and its relationship to activation of tissue
      specific transcription.
AB  - We examined DNA methylation throughout the endogenous murine testis-specific
      phosphoglycerate kinase (Pgk2) gene and in human PGK2 promoter/CAT reporter
      transgenes in mouse spermatogenic cells before, during, and following the period
      of active transcription of this gene. We observed the gradual development of a
      domain of demethylation beginning over the promoter and then expanding
      approximately 1 kilobase in each direction within the endogenous Pgk2 gene. This
      demethylation domain develops in the absence of DNA replication and precedes
      other molecular changes that potentiate tissue-specific activation of this gene.
      Studies with transgenes show that a signal residing in the Pgk2 core promoter
      directs this gene-, cell type-, and stage-specific demethylation process. These
      results are consistent with a model in which regulated, tissue- and gene-specific
      demethylation initiates a cascade of subsequent molecular events required for
      tissue-specific activation of transcription during spermatogenesis in vivo.

PMID- 15140799
TI  - Social regulation of the electrical properties of gonadotropin-releasing hormone
      neurons in a cichlid fish (Astatotilapia burtoni).
AB  - Variation in reproductive capacity is common across the lives of all animals. In
      vertebrates, hypothalamic neurons that secrete GnRH are a primary mediator of
      such reproductive plasticity. Since social interactions suppress gonadal maturity
      in the African cichlid fish, Astatotilapia (Haplochromis) burtoni, we
      investigated whether the electrical properties of GnRH neurons were also socially
      regulated. Adult A. burtoni males are either territorial (T) and reproductively
      active or nonterritorial (NT) and reproductively regressed, depending upon their
      social environment. We compared the basic electrical properties of hypothalamic
      GnRH neurons from T and NT males using whole-cell electrophysiology in vitro.
      GnRH neurons were spontaneously active and exhibited several different activity
      patterns. A small fraction of neurons exhibited episodic activity patterns, which
      have been described in GnRH neurons from mammals. The type of activity pattern
      and spontaneous firing rate did not vary with reproductive capacity; however,
      several basic electrical properties were different. Neurons from T males were
      larger than those from NT males and had higher membrane capacitance and lower
      input resistance. In neurons from NT males, action potential duration was
      significantly longer and after-hyperpolarization characteristics were diminished,
      which led to a tendency for neurons from NT males to fire less rapidly in
      response to current injection. We predict this could serve to decrease GnRH
      release in NT males. These data are the first electrophysiological
      characterization of hypothalamic GnRH neurons in a nonmammalian species and
      provide evidence for several changes in electrical properties with reproductive
      state.

PMID- 15140798
TI  - Maternal nutrient restriction reduces concentrations of amino acids and
      polyamines in ovine maternal and fetal plasma and fetal fluids.
AB  - Amino acids and polyamines are essential for placental and fetal growth, but
      little is known about their availability in the conceptus in response to maternal
      undernutrition. We hypothesized that maternal nutrient restriction reduces
      concentrations of amino acids and polyamines in the ovine conceptus. This
      hypothesis was tested in nutrient-restricted ewes between Days 28 and 78
      (experiment 1) and between Days 28 and 135 (experiment 2) of gestation. In both
      experiments, ewes were assigned randomly on Day 28 of gestation to a control
      group fed 100% of National Research Council (NRC) nutrient requirements and to an
      nutrient-restricted group fed 50% of NRC requirements. Every 7 days beginning on
      Day 28 of gestation, ewes were weighed and rations adjusted for changes in body
      weight. On Day 78 of gestation, blood samples were obtained from the uterine
      artery and umbilical vein for analysis. In experiment 2, nutrient-restricted ewes
      on Day 78 of gestation either continued to be fed 50% of NRC requirements or were
      realimented to 100% of NRC requirements until Day 135. Fetal weight was reduced
      in nutrient-restricted ewes at both Day 78 (32%) and Day 135 (15%) compared with
      controls. Nutritional restriction markedly reduced (P < 0.05) concentrations of
      total alpha-amino acids (particularly serine, arginine-family amino acids, and
      branched-chain amino acids) and polyamines in maternal and fetal plasma and in
      fetal allantoic and amniotic fluids at both mid and late gestation.
      Realimentation of nutrient-restricted ewes increased (P < 0.05) concentrations of
      total alpha-amino acids and polyamines in all the measured compartments and
      prevented intrauterine growth retardation. These novel findings demonstrate that
      50% global nutrient restriction decreases concentrations of amino acids and
      polyamines in the ovine conceptus that could adversely impact key fetal
      functions. The results have important implications for understanding the
      mechanisms responsible for both intrauterine growth retardation and developmental
      origins of adult disease.

PMID- 15140800
TI  - Gene expression profiling of embryonic stem cells leads to greater understanding
      of pluripotency and early developmental events.
AB  - Embryonic stem cells are characterized by their ability to propagate indefinitely
      in culture, maintaining a normal karyotype and their undifferentiated state. They
      have the potential of differentiating into any specialized cell type in the body.
      An understanding of the transcriptional profile related to pluripotency and early
      development is necessary to better tap their developmental potential and also
      maintain their undifferentiated phenotype. Currently, several techniques are in
      use to ascertain the gene expression profile of embryonic stem cells. This review
      summarizes the information generated using microarray and other approaches on the
      gene expression analyses of stem cells in both mouse and human cell lines. We
      also discuss specific approaches useful in future studies aimed at further
      deciphering the pluripotent nature of human embryonic stem cells.

PMID- 15140801
TI  - What's special about psychiatric subspecialties?

PMID- 15140802
TI  - Psychosomatic medicine: a new psychiatric subspecialty.
AB  - OBJECTIVE: Psychosomatic medicine, also known as consultation-liaison psychiatry,
      received approval as a subspecialty field of psychiatry by the American Board of
      Medical Specialties in the spring of 2003. This represents a crucial step in the
      development of the field of psychosomatic medicine and recognition by leaders in
      the fields of medicine and psychiatry of its importance. METHODS: The field was
      developed in response to evidence suggesting that a high prevalence of
      psychiatric disorders exists in patients with complex medical illnesses and that
      diagnosis and management of these disorders in this population is critical yet
      frequently complicated by the medical illnesses themselves. RESULTS:
      Psychosomatic medicine psychiatrists have developed specialized expertise in
      addressing these issues. CONCLUSION: The approval of subspecialty status for
      psychosomatic medicine will help promote the psychiatric care of patients with
      complex medical, surgical, obstetrical and neurological conditions, as well as
      foster further improvements in the quality of training and research in this
      important area.

PMID- 15140803
TI  - Subspecialty certification by the American Board of Psychiatry and Neurology.
AB  - OBJECTIVE: The authors describe the approval processes for subspecialties and the
      mechanisms for certification and recertification and review the status of
      training programs and numbers of diplomates with subspecialty certification.
      METHODS: Published information and relevant data bases were reviewed. To date,
      5,327 child and adolescent psychiatry, 2,595 geriatric psychiatry, 1,854
      addiction psychiatry, and 1,384 forensic psychiatry certificates have been
      awarded. In clinical neurophysiology and pain medicine, specialties that are
      primarily for neurologists and child neurologists, 21 and 28 psychiatrists,
      respectively, have been certified. There are 113 residency programs in child and
      adolescent psychiatry, 62 in geriatric psychiatry, 43 in addiction psychiatry,
      and 40 in forensic psychiatry. There are no psychiatry-based training programs in
      clinical neurophysiology and pain medicine. While this may not be of concern for
      clinical neurophysiology, it may lessen psychiatry's contribution to pain
      medicine. RESULTS: The ABPN took a conservative approach to establishing
      subspecialty certification in psychiatry. CONCLUSION: It is expected that
      subspecialists will enhance patient care through their clinical activities as
      well as through teaching and research.

PMID- 15140804
TI  - Assessment of competency in child and adolescent psychiatry training.
AB  - OBJECTIVE: Residency training programs in all areas of medicine are required to
      identify core competencies expected of all graduates and develop methods to
      assess and ensure attainment of these competencies. To assist with this process
      for residency programs in child and adolescent psychiatry, the Work Group on
      Training and Education of the American Academy of Child and Adolescent Psychiatry
      has developed several principles of the assessment process and compiled a variety
      of assessment methodologies for use in assessing competency. The principles of
      assessment include 1) residents should share responsibility for assessment; 2)
      assessment should be an open, ongoing and predictable process; 3) a wide range of
      evaluators should be utilized in the process; 4) residents should demonstrate
      competency in a variety of formats; 5) the goal is for 100% of residents to
      achieve core competencies. METHODS: Sample methods of assessment are provided in
      the report with special attention to how the method could be used in child and
      adolescent psychiatry. CONCLUSION: A multi-method, multi-evaluator for process of
      assessment is recommended.

PMID- 15140805
TI  - Community psychiatrists who see geriatric patients: what's training got to do
      with it?
AB  - OBJECTIVE: This study examines the issues influencing psychiatrists' decisions to
      provide care to the under-served geriatric population. METHODS: Community-based
      psychiatrists who see geriatric patients participated in focus group discussions
      exploring factors that influence the characteristics of their current practices.
      RESULTS: Personal themes, environmental issues and quality of residency training
      emerged as important factors interacting in eventual practice choice. Major
      influences within training programs included teachers, diverse patient exposure
      and high-quality essential skills teaching. CONCLUSION: Residency program
      curricula might capitalize on these to better prepare residents and enhance the
      likelihood of graduates eventually choosing to incorporate geriatric patients
      into their practices.

PMID- 15140806
TI  - Cross-cultural issues in forensic psychiatry training.
AB  - OBJECTIVE: Forensic psychiatry was officially recognized as a subspecialty by the
      American Board of Medical Specialties in the 1990's. In 1994, the American Board
      of Psychiatry and Neurology (ABPN) gave its first written examination to certify
      forensic psychiatrists. In 1996, the Accreditation Council for Graduate Medical
      Education (ACGME) began to officially accredit one-year residency experiences in
      forensic psychiatry, which follow a 4-year residency in general psychiatry. The
      extra year of training, colloquially known as a fellowship, is required for
      candidates who wish to receive certification in the subspecialty of forensic
      psychiatry; since 2001, completion of a year of training in a program accredited
      by ACGME has been required for candidates wishing to take the ABPN forensic
      psychiatry subspecialty examination. With the formal recognition of the
      subspecialty of forensic psychiatry comes the need to examine special issues of
      cultural importance which apply specifically to forensic psychiatry training.
      METHODS: This paper examines the current literature on cross-cultural issues in
      forensic psychiatry, sets out several of the societal reasons for the importance
      of emphasizing those issues in forensic psychiatric training, and discusses how
      those issues are addressed in the curriculum of one forensic psychiatry
      fellowship at the Medical College of Wisconsin (MCW). CONCLUSION: While much has
      been written about cross-cultural issues in general psychiatry, very little has
      appeared in the literature on the topic of cross-cultural issues in forensic
      psychiatry.

PMID- 15140807
TI  - Teaching forensic psychiatry to general psychiatry residents.
AB  - OBJECTIVE: The Accreditation Council on Graduate Medical Education (ACGME)
      requires that general psychiatry residency training programs provide trainees
      with exposure to forensic psychiatry. Limited information is available on how to
      develop a core curriculum in forensic psychiatry for general psychiatry residents
      and few articles have been published on the topic. METHODS: The objective of this
      article is to provide an overview of forensic psychiatry topics likely to be of
      benefit to general psychiatry residents. RESULTS: The article is intended to be a
      springboard for future development of forensic curricula suitable for residents
      rather than a blueprint for an educational program. CONCLUSION: Although most
      general psychiatry residents will not specialize in forensic psychiatry, a
      working knowledge of basic concepts in forensic psychiatry should be considered
      an important component of general psychiatry education.

PMID- 15140808
TI  - Addressing the effects of culture on the boundary-keeping practices of psychiatry
      residents educated outside of the United States.
AB  - OBJECTIVE: The author sought to develop a curriculum for international medical
      graduate (IMG) psychiatry residents that addresses their culture-based deviations
      from normative boundary-keeping practices common to U.S.-based psychotherapy
      practices. METHODS: A group consisting of 12 IMG psychiatry residents and one
      United States graduate (USG) participated in a curriculum consisting of eight
      monthly, 1-hour seminars. An eight-item, Likert-type 7-point scale, post-then-pre
      questionnaire assessed the instructional impact of the curriculum. RESULTS:
      Responses indicated that participation in the curriculum significantly increased
      the IMG residents' levels of confidence with respect to boundary theory and
      practice. CONCLUSION: International medical graduates confidence levels regarding
      psychotherapeutic boundaries can be significantly increased through participation
      in a curriculum that addresses cultural differences.

PMID- 15140809
TI  - Workforce information on addiction psychiatry graduates.
AB  - OBJECTIVE: The aim of this paper is to report workforce information about
      graduates from accredited training programs in addiction psychiatry. METHODS: As
      of June 30, 2002 there were 44 ACGME-accredited addiction psychiatry programs.
      The author asked the directors of these programs to complete a workforce survey
      about their graduates. RESULTS: Seventy-three percent of program directors
      responded, providing information about 186 addiction psychiatrists. Forty-one
      percent of the graduates were employed in academic settings. Sixty-four percent
      of graduates employed in clinical settings dealt primarily with substance abuse
      patients. A majority of respondents described graduates as satisfied with
      compensation packages. CONCLUSION: Addiction psychiatry offers opportunities in a
      variety of settings that allow new graduates to utilize their subspecialty
      training.

PMID- 15140810
TI  - Distance learning technologies in the training of psychiatry residents: a
      critical assessment.
AB  - OBJECTIVE: The advent of videoconferencing technology has created opportunities
      to pool educational resources across different training programs. METHODS: The
      authors surveyed participants and presenters in a seminar series utilizing
      interactive video-conferencing and a web-based course management system. RESULTS:
      Trainees with access to high-speed real-time connections rated their experience
      more highly compared with those who used slower web streaming technology,
      particularly with regard to the sound quality. CONCLUSIONS: Specific
      recommendations on optimizing the use of video-conferencing and web-based course
      management tools in the training of residents are offered.

PMID- 15140811
TI  - An interviewing course for a psychiatry clerkship.
AB  - OBJECTIVE: Taking a psychiatric history is a key educational objective in the
      psychiatry clerkship. Medical students arrive on psychiatry clerkships unprepared
      for the unique challenges of psychiatric interviewing. This paper describes an
      interviewing course for psychiatry clerks that combines practice, observation,
      and feedback in a small group setting. METHODS: A quasi-experimental cohort
      design with medical student self-ratings as the dependent variable. RESULTS:
      Students' self-perceived skill in interviewing and differential diagnosis
      improved more than students who did not have the interviewing course. Students'
      self-perceived skills also correlated significantly with the number of times they
      observed interviews. CONCLUSION: Clerkship directors in psychiatry should provide
      students with opportunities to practice interviewing skills, observe interviews,
      and receive feedback.

PMID- 15140812
TI  - "The Matrix": An allegory of the psychoanalytic journey.
AB  - OBJECTIVE: "The Matrix" has been a huge commercial and critical success and has
      spawned a series of books and essays exploring the philosophical and religious
      themes in the story. METHODS: The authors propose is that "The Matrix" can be
      interpreted as an allegory for an individual's journey into spiritual and mental
      health, achieved by overcoming one's intrapsychic conflicts with the help of
      psychodynamic psychotherapy or psychoanalysis. RESULTS: Neo's story parallels the
      journey undertaken by the individual who chooses to enter psychotherapy and
      illustrates several themes of analytic psychotherapy, its benefits, and
      liabilities. CONCLUSION: The movie may therefore serve as a teaching tool for
      psychiatric residents about the goals, functions, and intricacies of
      psychodynamic psychotherapy.

PMID- 15140813
TI  - Cholinergic enhancement of frontal lobe activity in mild cognitive impairment.
AB  - Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD)
      and other conditions, but no controlled functional MRI studies have examined
      where their effects occur in the brain. We examined the effects of donepezil
      hydrochloride (Aricept) on cognition and brain activity in patients with amnestic
      mild cognitive impairment (MCI), a diagnosis associated with a high risk of
      developing AD. Nine older adults with MCI were compared with nine healthy,
      demographically matched controls. At baseline, patients showed reduced activation
      of frontoparietal regions relative to controls during a working memory task.
      After stabilization on donepezil (5.7 +/- 1.7 weeks at 10 mg) patients showed
      increased frontal activity relative to unmedicated controls, which was positively
      correlated with improvement in task performance (r = 0.49, P = 0.05) as well as
      baseline hippocampal volume (r = 0.62, P < 0.05). The patients' overall cognitive
      function was stable or improved throughout the study. Short-term treatment with a
      cholinesterase inhibitor appears to enhance the activity of frontal circuitry in
      patients with MCI, and this increase appears to be related to improved cognition
      and to baseline integrity of the hippocampus. These relationships have
      implications for understanding the mechanisms by which cognition-enhancing
      medications exert their effects on brain function and for the use of functional
      MRI in early detection and treatment monitoring of AD and MCI.

PMID- 15140814
TI  - The dynamic range of digital radiographic systems: dose reduction or risk of
      overexposure?
AB  - OBJECTIVES: To investigate the range of diagnostically acceptable digital
      radiographs and film as a function of exposure time, as well as the relationship
      to dose reduction and consequences for dental practice. METHODS: Five systems for
      intraoral radiography were used to take a series of radiographs, with increasing
      exposure times, of five different dry bone specimens. Seven observers evaluated
      the 25 series of radiographs. The observers had to determine which radiographs of
      each series were acceptable for dental diagnostics and which radiograph of each
      series they preferred. RESULTS: For Ektaspeed Plus film, the exposure time for
      the preferred radiograph was 0.52 s, with a range of diagnostically acceptable
      radiographs from 0.23-1.02 s. The preferred radiograph of the solid-state systems
      required less radiation than film (Sirona, 0.13 s; MPDx 0.35 s). The exposure
      range of these systems is narrow. In contrast, the exposure range of the phosphor
      plate systems is very wide. The preferred radiograph of the phosphor plate
      systems required high exposure (Digora, 1.21 s; Gendex DenOptix, 1.16 s).
      CONCLUSIONS: All digital systems require less exposure than film for
      diagnostically acceptable radiographs, but this is less obvious for preferred
      radiographs. Solid-state systems alert the dentist when a too long exposure time
      is used by a lack of image quality; phosphor plate systems, however, produce good
      quality radiographs even at high exposure times, which may result in an
      unnecessarily high dose.

PMID- 15140816
TI  - Precision and accuracy of CT-based measurements of masticatory muscles in
      patients with hemifacial microsomia.
AB  - OBJECTIVE: The objective of this study was to quantitatively assess masticatory
      muscle volumes in patients with hemifacial microsomia. Until recently, this
      congenital malformation was only studied in terms of restoring bony and skin
      morphologies. Study of the masticatory muscles, however, adds a new dimension.
      MATERIALS AND METHODS: Contiguous 1.5 mm CT scans were made using a Philips
      Tomoscan 350 in six patients with hemifacial microsomia and in one patient
      without asymmetry. These CT scans were processed by a Cemax 1500X 3D workstation.
      The volume of the masseter, temporal, and medial and lateral pterygoid muscles
      was measured from CT scans using three-dimensional (3D) segmentation followed by
      3D imaging. The precision and accuracy of measurements of masticatory muscle
      volumes were investigated. The precision of 3D imaging was assessed by carrying
      out repeated measurements by two observers. The accuracy of the volume
      determination technique was assessed by scanning a piece of porcine muscle tissue
      with a known volume. RESULTS: Intraobserver repeatability was near perfect, with
      the lowest alpha being 0.96 (for the medial pterygoid muscle). All interobserver
      correlations were high (>0.99). The accuracy of the method of measurement
      demonstrated differences ranging from 2.3% to 4.4%. CONCLUSION: Craniofacial soft
      tissue measurements obtained from CT scans in patients with hemifacial microsomia
      were accurate and reproducible but time consuming.

PMID- 15140815
TI  - Evaluation of endodontic files in digital radiographs before and after employing
      three image processing algorithms.
AB  - OBJECTIVES: Two digital image processing algorithms, one aimed at correction for
      exponential attenuation and one at correction for visual response, have been
      developed. The aims of the present study were to test whether digital radiographs
      processed with these algorithms improve determination of the length of endodontic
      files and whether such processed radiographs are comparable with the radiographs
      processed with a default image processing method employed by one commercially
      available digital intraoral system. METHODS: A dried human skull embedded in an
      acrylic compound was used for exposing radiographs of the upper and lower
      premolars and molars with endodontic files (Kerr files size 10 and size 15)
      positioned to the full length of the roots or 1.5 mm short of it. Radiographs
      were then processed in three sets. In one set, the radiographs were processed to
      compensate for exponential attenuation and the response of the human visual
      system. In the second, the radiographs were processed with the same compensation
      but with an additional shift in grey levels so that the output luminance in
      dentin at root tips corresponds to the mean of the luminance range of a computer
      monitor. In the third, the radiographs were processed with the default processing
      method in the Sidexis program. Ten viewers evaluated all radiographs. Receiver
      operating characteristic (ROC) curves were obtained and areas under the curves
      were calculated. RESULTS: For file size 10, ROC curves for processed radiographs
      were higher than that for originals, while for file size 15, ROC curves for
      processed and original radiographs were close to each other. Significant
      differences were found between processed and original radiographs regarding areas
      under ROC curves for file size 10 but not between the differently processed
      radiographs. For file size 15, no significant differences were found. CONCLUSION:
      Radiographs processed to correct for attenuation and visual response may improve
      determination of the length of thin endodontic files. Such processed radiographs
      are comparable with the radiographs processed with the default processing method
      in the Sidexis program.

PMID- 15140817
TI  - Radiographic examination of dentigerous cysts in the transitional dentition.
AB  - OBJECTIVES: To examine radiographically the relationship between the deciduous
      tooth and dentigerous cyst of the permanent successor during the transitional
      dentition. METHODS: From a retrospective review of all patients who visited our
      institution from April 1988 to August 2001, 70 patients under 16 years of age who
      had histologically confirmed dentigerous cysts that had developed from the
      central incisor to the second premolar were identified. These 70 patients were
      investigated using panoramic and periapical radiographs. RESULTS: In most cases
      (54 cases; 77.1%) the cyst was in the premolar region. Of the 54 premolars with
      dentigerous cysts, the overlying deciduous tooth had already been lost in 7
      cases. Of the 47 remaining premolars with associated deciduous tooth, 35 (74.5%)
      had bone resorption of the periapical or bifurcation region, or irregular
      resorption of the associated deciduous tooth. Of the remaining 12 deciduous teeth
      with no periapical lesions, 9 had been treated with root canal therapy. Thus, 44
      of these 47 cases (93.6%) had the possibility of inflammation at the deciduous
      tooth associated with the dentigerous cyst. Evidence from one case in the present
      study suggesting the process by which cyst development occurs is also given.
      CONCLUSION: Inflammatory change at the apex of the deciduous tooth may bring on a
      dentigerous cyst of the permanent successor.

PMID- 15140818
TI  - Effect of beam energy and filtration on the signal-to-noise ratio of the Dexis
      intraoral X-ray detector.
AB  - OBJECTIVE: To evaluate the signal-to-noise ratio (SNR) of the Dexis charge
      coupled device (CCD) intraoral X-ray detector, with special reference to the
      influence of beam energy and filtration. MATERIAL AND METHODS: Digital
      radiographic images were made of a nine-step dental aluminium step wedge using a
      Dexis intraoral detector. The X-ray generator was a GE 1000 operating at 10 mA
      with 2.7 mm aluminium filtration. The peak tube voltage settings applied were 50
      kVp, 60 kVp, 70 kVp, 80 kVp and 90 kVp. Various exposure times were used at each
      beam energy and the exposures (in micro C kg(-1)) were determined in each case
      using a 3 cl beryllium-windowed ionization chamber. SNR was defined using the
      surrogate measure of mean pixel value (surrogate for signal) divided by the
      standard deviation of the pixel value (surrogate for noise). SNRs were measured
      at separate regions of interest (ROIs) at the centre and at both sides of the
      detector for each aluminium step as well as without the step. RESULTS: For beam
      energies of 50 kVp and 60 kVp, the estimated SNR improved both with increased
      exposure and with increased filtration (thickness of the aluminium step), and
      image saturation did not occur within the exposure time range permitted by the
      Dexis software. At 70 kVp and above, the SNR was optimized in the middle of the
      exposure range: 4 micro C kg(-1) with 290:1 at the ninth step (13.5 mm Al) for 70
      kVp; 3.5 micro C kg(-1) with 240:1 at the ninth step (13.5 mm Al) for 80 kVp; 3.5
      micro C kg(-1) with 160:1 at the ninth step (13.5 mm Al) for 90 kVp. Saturation
      did occur at these beam energies within the exposure time range permitted by the
      Dexis software. CONCLUSION: For the Dexis intraoral radiographic imaging system,
      estimated SNR improved both with higher filtration and with lower kVp. The Dexis
      detector was capable of generating acceptable images of the step wedge at a wide
      range of kVp settings.

PMID- 15140819
TI  - Array geometry for assessment of mandibular implant position using tuned aperture
      computed tomography (TACT).
AB  - OBJECTIVE: To evaluate observer faciolingual depth and vertical depth reading
      errors when using various X-ray beam array geometries to make basis images for
      tomosynthetic reconstruction using tuned aperture computed tomography (TACT).
      MATERIALS AND METHODS: Tissue-equivalent models were constructed to replicate the
      position of dental implants in relation to simulated mandibular canals. X-ray
      beam geometries used to acquire the basis images for TACT(TM) integration
      included horizontal linear, vertical linear, and symmetric and asymmetric conical
      arrays. Twenty-one dentists trained in the use of TACT acted independently as
      observers. Tasks included: (1) determination of the relative position of the
      implant in relation to the simulated canal; and (2) measurement of the vertical
      depth and faciolingual (lateral) depth dimensions between these two structures.
      As the study did not involve repeated measures (only one measure was obtained
      from each observer on each of the two dependent variables), data for faciolingual
      depth and vertical depth reading errors were analysed using a one-way analysis of
      variance (ANOVA) with Tukey's honestly significant different (HSD) procedure.
      RESULTS: Errors in determining the relative position of the implant to the
      simulated canal were most frequent when the linear horizontal projection geometry
      was employed for producing basis images (57% error for model #2 where the implant
      was lingually placed). The mean measurement errors for TACT images constructed
      using the various different projection arrays depended both on the structural
      relationship of anatomic features and the employed beam array geometry.
      CONCLUSION: Conical beam arrays are preferred over linear beam arrays for
      constructing basis images used with TACT for the purpose of correlating the
      position of a mandibular dental implant in relation to the mandibular canal. They
      more consistently allowed the observers to establish a measurement of the
      faciolingual relationship of the implant to the canal. For vertical depth
      measurement of the relationship of a mandibular dental implant to the mandibular
      canal, TACT does not appear to have any advantage over individual simple
      transmission radiographic images.

PMID- 15140820
TI  - Quality of film-based and digital panoramic radiography.
AB  - OBJECTIVES: To compare the image quality of panoramic radiographs obtained with
      storage phosphor plate and screen-film systems. METHODS: Panoramic radiographs
      were taken in 60 patients both with film and with a storage phosphor plate system
      (30 with DenOptix (Dentsply/Gendex) and 30 with Digora PCT). The images were
      obtained with either the Cranex Tome or the Scanora multimodal X-ray unit. The
      screen-film combination was Lanex medium/Curix Ortho HT-G. The digital images
      were displayed as 8-bit images with a 300 dpi resolution on a 19" monitor and the
      film images were placed on a light box adjacent to the screen. Ten observers
      evaluated diagnostic image quality by means of visual grading analysis of
      different anatomical structures. The structures were scored as being visualized
      much better (5), better (4), equal (3), worse (2) or much worse (1) in the
      digital images than in the film images. The mean number of patients receiving the
      different scores was calculated. Statistical methods used were Wilcoxon sign rank
      test and Mann-Whitney test. RESULTS: On average, visualization was equal in 19 of
      the 30 patients imaged using Digora PCT; in 10 it was worse. The corresponding
      values for DenOptix were 20 and 9. The difference between the film-based and the
      digital images was small but statistically significant (P<0.0001). The difference
      between the two image plate systems was not statistically significant (P>/=0.17).
      CONCLUSIONS: It was concluded that digital panoramic radiographs are equivalent
      to film-based images for most purposes.

PMID- 15140821
TI  - The impact of image compression on diagnostic quality of digital images for
      detection of chemically-induced periapical lesions.
AB  - OBJECTIVES: To test the hypothesis that there is no significant difference in the
      detectability of chemically-induced periapical lesions between a non-compressed
      image and one subjected to a Joint Photographic Experts Group (JPEG) lossy
      compression technique at a ratio of 23:1 or less. METHOD: Chemically-induced
      periapical lesions were created by placing a solution of 70% perchloric acid at
      the apex of extracted teeth in 13 human jaw cadaver specimens. Acid was applied
      in seven incremental time periods from 0-32 h. Extracted teeth were replaced in
      the socket and images were made using the Schick CDR digital sensor. Using a JPEG
      lossy compression algorithm, five compression ratios of 2:1, 14:1, 23:1, 28:1 and
      47:1 were applied to the images. Images were viewed three times by three
      observers who ranked the presence or absence of a lesion at three sites, the
      mesial area, distal area and apex of the tooth, on a 5-point confidence scale.
      Intraobserver and interobserver agreement and agreement between the compressed
      and the original images were assessed with intraclass correlation coefficients
      (ICCs). RESULTS: Overall ICCs for measuring intraobserver agreement using all
      images were 0.77, 0.84, and 0.50 for the three observers, respectively. The
      overall ICC for assessing agreement between observers was 0.57. There was no
      significant difference (P>0.05) between compressed and original images for any
      site at compression ratios of 2:1, 23:1 and 28:1. There were significant
      differences for a compression ratio of 47:1. CONCLUSION: JPEG compression does
      not impact detectability of artificial periapical lesions at low and moderate
      compression ratios up to and including 28:1.

PMID- 15140822
TI  - Virtual reality for simulation of radiographic projections: validation of
      projection geometry.
AB  - OBJECTIVE: To develop a software for virtual reality (VR) simulation of X-ray
      images based on perspective projections through a patient model derived from data
      from a CT examination and to evaluate the accuracy in the projection geometry
      obtained by the software. METHODS: A VR software was developed on a personal
      computer, with models of a patient, an X-ray machine and a detector. The model of
      the patient was derived from data from a CT examination of a dry skull. Simulated
      radiographic images of the patient model could be rendered as perspective
      projections based on the relative positions between the models. The projection
      geometry of the software was validated by developing an artificial CT data set
      containing high attenuation points as objects to be imaged. The accuracy in
      projection geometry was evaluated in a systematic way. The distances between two
      dots, representing the projected test points in the simulated radiographic
      images, were measured. They were compared with theoretical calculations of the
      corresponding distances using traditional mathematical tools. RESULTS: The
      difference between the simulated and calculated projected distances never
      exceeded 0.5 mm. The error in simulated projected distances was in most cases
      within 1%. No systematic errors were revealed. CONCLUSION: The software,
      developed for personal computers, can produce simulated X-ray images with high
      geometric accuracy based on perspective projections through a CT data set. The
      software can be used for simulation of radiographic examinations.

PMID- 15140824
TI  - Maxillary unicystic ameloblastoma.
AB  - The authors present the case of a 17-year-old White male patient complaining of
      enlargement in the gingival region and the fundus of the left maxillary anterior
      vestibular sulcus. The clinicopathological diagnosis was plexiform unicystic
      ameloblastoma. With this report, the authors illustrate the importance and
      complexity of a differential diagnosis of lesions with a cystic aspect in the
      anterior region of the maxilla, among them inflammatory radicular cysts,
      odontogenic keratocysts, adenomatoid odontogenic and unicystic ameloblastoma.

PMID- 15140823
TI  - Characteristics of a newly developed dentomaxillofacial X-ray cone beam CT
      scanner (CB MercuRay): system configuration and physical properties.
AB  - OBJECTIVE: The purpose of this paper is to present the system configuration and
      physical properties of a new dentomaxillofacial X-ray cone beam CT system (CB
      MercuRay) being developed. METHODS: The system consists of an image intensifier
      and a cone beam X-ray source. There are two different models of this system, each
      with a different size image intensifier, 9" or 12". Each system has three field
      of view (FOV) modes. The 12" system has facial (F), panoramic (P) and implant (I)
      FOV modes. The 9" system has P, I and dental (D) modes. Images produced by these
      systems consist of 512 x 512 x 512 isotropic voxels. Physical properties such as
      resolution, noise and distortion of the images were evaluated in this study.
      Modulation transfer function (MTF) was measured using Boone's method. Image noise
      was measured as the standard deviation of the CT value in water. Circularity of
      the axial images yielded by the two models was measured using an 8 mm diameter
      acrylic pipe phantom. RESULTS: The resolving power at a MTF of 0.1 in the D mode
      was over 2.0 lp mm(-1), suggesting that this system yields images of high
      resolution. The standard deviation of the CT value in water was approximately 80,
      which is thought to be greater than that of conventional CT. The circularity of
      images of the pipe phantom was 99% of the ideal value. CONCLUSION: This study
      shows that our newly developed cone beam CT system produces high resolution three
      dimensional volumetric images that will be useful for the examination of
      dentomaxillofacial disorders.

PMID- 15140825
TI  - Mandibular ramus-related Stafne's bone cavity.
AB  - Mandibular bone depressions located on the lingual/buccal aspect of the
      mandibular ramus are the rarest variants of the so-called Stafne's bone cavities,
      or major salivary gland-related depressions, with only 17 cases reported in the
      literature including both clinical cases and archaeological specimens. We report
      the case of a 14-year-old male patient who sought clinical assistance complaining
      of a hard expansion on the lower left premolar-molar region. Apart from a
      unilocular radiolucent lesion between the lower left second premolar and first
      molar, a panoramic radiograph showed another radiolucent lesion located in the
      right mandibular ramus, at the level of the mandibular foramen. Computed
      tomography (CT) revealed an expansile lesion in the left mandibular body, later
      diagnosed as a simple bone cyst through surgical exploration. The three
      dimensional CT volume rendering reconstructed image showed that the second
      lesion, located on the lingual aspect of the ascending ramus, was an actual
      cortical bone defect, which was diagnosed as a mandibular ramus-related Stafne's
      bone cavity. Considering the young age of the patient, the size of the defect,
      the recognizedly slow development of mandibular bone defects and, above all, the
      location of the bone defect under discussion, we believe it to have a congenital
      rather than a developmental origin (i.e. it was caused by a focal failure during
      intramembranous ossification of the mandible). If this is the case, mandibular
      bone depressions should not be seen exclusively as salivary gland-related bone
      defects.

PMID- 15140826
TI  - Cell surface overexpression of galectin-3 and the presence of its ligand 90k in
      the blood plasma as determinants in colon neoplastic lesions.
AB  - Galectins are a family of beta-galactoside binding molecules involved in cell-
      extracellular matrix adhesion processes. Specifically, Galectin-3 (Gal-3), one of
      the members of this family of molecules plays a role in cell adhesion processes
      as well as in cell survival or apoptosis. Gal-3 was also hypothesized to
      represent a useful tool in tumor characterization, for example, in thyroid
      tumors. We report herein the results obtained by evaluating Gal-3 expression of
      colon cells from human adenomas and adenocarcinomas with two different
      methodologies: immunohistochemistry and flow cytometry of living dispersed cells.
      We found that (1) the expression of Gal-3 was significantly increased on the
      surface of cells from adenomas with respect to normal mucosa from the same
      patient; (2) Gal-3 ligand, 90k molecule, was increased in the blood plasma from
      patients with both adenomatous and adenocarcinomatous lesions; and (3) Gal-3
      overexpression was not related with the presence of K-ras mutation. Altogether
      these results clearly indicate that the evaluation of Gal-3 expression (and of
      its ligand, 90k) can be of interest in the characterization of nonmalignant and
      malignant colon cancers.

PMID- 15140827
TI  - Predicting protein complex membership using probabilistic network reliability.
AB  - Evidence for specific protein-protein interactions is increasingly available from
      both small- and large-scale studies, and can be viewed as a network. It has
      previously been noted that errors are frequent among large-scale studies, and
      that error frequency depends on the large-scale method used. Despite knowledge of
      the error-prone nature of interaction evidence, edges (connections) in this
      network are typically viewed as either present or absent. However, use of a
      probabilistic network that considers quantity and quality of supporting evidence
      should improve inference derived from protein networks. Here we demonstrate
      inference of membership in a partially known protein complex by using a
      probabilistic network model and an algorithm previously used to evaluate
      reliability in communication networks.

PMID- 15140828
TI  - Complete MHC haplotype sequencing for common disease gene mapping.
AB  - The future systematic mapping of variants that confer susceptibility to common
      diseases requires the construction of a fully informative polymorphism map.
      Ideally, every base pair of the genome would be sequenced in many individuals.
      Here, we report 4.75 Mb of contiguous sequence for each of two common haplotypes
      of the major histocompatibility complex (MHC), to which susceptibility to >100
      diseases has been mapped. The autoimmune disease-associated-haplotypes HLA-A3-B7
      Cw7-DR15 and HLA-A1-B8-Cw7-DR3 were sequenced in their entirety through a
      bacterial artificial chromosome (BAC) cloning strategy using the consanguineous
      cell lines PGF and COX, respectively. The two sequences were annotated to
      encompass all described splice variants of expressed genes. We defined the
      complete variation content of the two haplotypes, revealing >18,000 variations
      between them. Average SNP densities ranged from less than one SNP per kilobase to
      >60. Acquisition of complete and accurate sequence data over polymorphic regions
      such as the MHC from large-insert cloned DNA provides a definitive resource for
      the construction of informative genetic maps, and avoids the limitation of
      chromosome regions that are refractory to PCR amplification.

PMID- 15140829
TI  - Putative ancestral origins of chromosomal segments in individual african
      americans: implications for admixture mapping.
AB  - Theoretically, markers that distinguish European from West African ancestry can
      be used to examine the origin of chromosomal segments in individual African
      Americans. In this study, putative ancestral origin was examined by using
      haplotypes estimated from genotyping 268 African Americans for 29 ancestry
      informative markers spaced over a 60-cM segment of chromosome 5. Analyses using a
      Bayesian algorithm (STRUCTURE) provided evidence that blocks of individual
      chromosomes derive from one or the other parental population. In addition,
      modeling studies were performed by using hidden real marker data to simulate
      patient and control populations under different genotypic risk ratios. Ancestry
      analysis showed significant results for a genotypic risk ratio of 2.5 in the
      African American population for modeled susceptibility genes derived from either
      putative parental population. These studies suggest that admixture mapping in the
      African American population can provide a powerful approach to defining genetic
      factors for some disease phenotypes.

PMID- 15140830
TI  - A Plasmodium gene family encoding Maurer's cleft membrane proteins: structural
      properties and expression profiling.
AB  - Upon invasion of the erythrocyte cell, the malaria parasite remodels its
      environment; in particular, it establishes a complex membrane network, which
      connects the parasitophorous vacuole to the host plasma membrane and is involved
      in protein transport and trafficking. We have identified a novel subtelomeric
      gene family in Plasmodium falciparum that encodes 11 transmembrane proteins
      localized to the Maurer's clefts. Using coimmunoprecipitation and shotgun
      proteomics, we were able to enrich specifically for these proteins and detect
      distinct peptides, allowing us to conclude that four to 10 products were present
      at a given time. Nearly all of the Pfmc-2tm genes are transcribed during the
      trophozoite stage; this narrow time frame of transcription overlaps with the
      specific stevor and rif genes that are differentially expressed during the
      erythrocyte cycle. The description of the structural properties of the proteins
      led us to manually reannotate published sequences, and to detect potentially
      homologous gene families in both P. falciparum and Plasmodium yoelii yoelii,
      where no orthologs were predicted uniquely based on sequence similarity. These
      basic proteins with two transmembrane domains belong to a larger superfamily,
      which includes STEVORs and RIFINs.

PMID- 15140831
TI  - Visualizing sequence similarity of protein families.
AB  - Classification of proteins into families is one of the main goals of functional
      analysis. Proteins are usually assigned to a family on the basis of the presence
      of family-specific patterns, domains, or structural elements. Whereas proteins
      belonging to the same family are generally similar to each other, the extent of
      similarity varies widely across families. Some families are characterized by
      short, well-defined motifs, whereas others contain longer, less-specific motifs.
      We present a simple method for visualizing such differences. We applied our
      method to the Arabidopsis thaliana families listed at The Arabidopsis Information
      Resource (TAIR) Web site and for 76% of the nontrivial families (families with
      more than one member), our method identifies simple similarity measures that are
      necessary and sufficient to cluster members of the family together. Our
      visualization method can be used as part of an annotation pipeline to identify
      potentially incorrectly defined families. We also describe how our method can be
      extended to identify novel families and to assign unclassified proteins into
      known families.

PMID- 15140832
TI  - Systems level insights into the stress response to UV radiation in the halophilic
      archaeon Halobacterium NRC-1.
AB  - We report a remarkably high UV-radiation resistance in the extremely halophilic
      archaeon Halobacterium NRC-1 withstanding up to 110 J/m2 with no loss of
      viability. Gene knockout analysis in two putative photolyase-like genes (phr1 and
      phr2) implicated only phr2 in photoreactivation. The UV-response was further
      characterized by analyzing simultaneously, along with gene function and protein
      interactions inferred through comparative genomics approaches, mRNA changes for
      all 2400 genes during light and dark repair. In addition to photoreactivation,
      three other putative repair mechanisms were identified including d(CTAG)
      methylation-directed mismatch repair, four oxidative damage repair enzymes, and
      two proteases for eliminating damaged proteins. Moreover, a UV-induced down
      regulation of many important metabolic functions was observed during light repair
      and seems to be a phenomenon shared by all three domains of life. The systems
      analysis has facilitated the assignment of putative functions to 26 of 33 key
      proteins in the UV response through sequence-based methods and/or similarities of
      their predicted three-dimensional structures to known structures in the PDB.
      Finally, the systems analysis has raised, through the integration of
      experimentally determined and computationally inferred data, many experimentally
      testable hypotheses that describe the metabolic and regulatory networks of
      Halobacterium NRC-1.

PMID- 15140833
TI  - Using the miraEST assembler for reliable and automated mRNA transcript assembly
      and SNP detection in sequenced ESTs.
AB  - We present an EST sequence assembler that specializes in reconstruction of
      pristine mRNA transcripts, while at the same time detecting and classifying
      single nucleotide polymorphisms (SNPs) occuring in different variations thereof.
      The assembler uses iterative multipass strategies centered on high-confidence
      regions within sequences and has a fallback strategy for using low-confidence
      regions when needed. It features special functions to assemble high numbers of
      highly similar sequences without prior masking, an automatic editor that edits
      and analyzes alignments by inspecting the underlying traces, and detection and
      classification of sequence properties like SNPs with a high specificity and a
      sensitivity down to one mutation per sequence. In addition, it includes
      possibilities to use incorrectly preprocessed sequences, routines to make use of
      additional sequencing information such as base-error probabilities, template
      insert sizes, strain information, etc., and functions to detect and resolve
      possible misassemblies. The assembler is routinely used for such various tasks as
      mutation detection in different cell types, similarity analysis of transcripts
      between organisms, and pristine assembly of sequences from various sources for
      oligo design in clinical microarray experiments.

PMID- 15140836
TI  - Peptide YY3-36 and satiety: clarity or confusion?

PMID- 15140834
TI  - Large-scale integration of human genetic and physical maps.
AB  - Genetic maps are used routinely in family-based linkage studies to identify the
      rough location of genes that influence human traits and diseases. Unlike physical
      maps, genetic maps are based on the amount of recombination occurring between
      adjacent loci rather than the actual number of bases separating them. Genetic
      maps are constructed by statistically characterizing the number of crossovers
      observed in parental meioses leading to the transmission of alleles to their
      offspring. Considerations such as the number of meioses observed, the
      heterozygosity and physical distance between the loci studied, and the
      statistical methods used can impact the construction and reliability of a genetic
      map. As is well known, poorly constructed genetic maps can have adverse effects
      on linkage mapping studies. With the availability of sequence-based maps, as well
      as genetic maps generated by different researchers (such as those generated by
      the Marshfield and deCODE groups), one can investigate the compatibility and
      properties of different maps. We have integrated information from the most
      current human genome sequence data (UCSC genome assembly Human July 2003) as well
      as 8399 microsatellite markers used in the Marshfield and deCODE maps to
      reconcile the these maps. Our efforts resulted in updated sex-specific genetic
      maps.

PMID- 15140837
TI  - Modulation of metabolic syndrome by fibroblast growth factor 19 (FGF19)?

PMID- 15140838
TI  - Ghrelin--satisfying a hunger for the mechanism.

PMID- 15140840
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15140839
TI  - The Endocrine Society Ethics Advisory Committee: ethical aspects of conflicts of
      interests, October 2003.

PMID- 15140842
TI  - National and school policies on restrictions of teacher smoking: a multilevel
      analysis of student exposure to teacher smoking in seven European countries.
AB  - The paper examines the association between restrictions on teacher tobacco
      smoking at school and student exposure to teachers who smoke during school hours.
      The data are taken from a European Commission-funded study 'Control of Adolescent
      Smoking' (the CAS study) in seven European countries. Multilevel modelling
      analyses were applied to investigate associations between national legislation
      concerning tobacco smoking in school, local school smoking restrictions and
      students' exposure to teachers who smoke at school. The analyses integrate data
      from three levels: national (types of policy and how restrictive they are),
      school (survey among teachers, n = 455) and student (survey among 15-year-old
      students, n = 10890). The results suggest that both national- and school-level
      policies on restriction of smoking among teachers are associated with a decreased
      probability of students reporting that they are exposed to teachers who smoke
      indoors, but an increased probability of being exposed to teachers smoking
      outdoors.

PMID- 15140843
TI  - Communication about smoking in Dutch families: associations between anti-smoking
      socialization and adolescent smoking-related cognitions.
AB  - Parents play an important role in the development of young people's smoking
      behavior, through the modeling effects of their own smoking status, through the
      ways they raise their children and through the ways they deal with smoking at
      home. The present study focused on anti-smoking socialization by, first,
      comparing the perspectives of both parents and an adolescent on eight indicators
      of anti-smoking socialization. In addition, we aimed to examine how these
      indicators of anti-smoking socialization are related to adolescent smoking
      related cognitions (e.g. attitudes, self-efficacy, intentions to smoke). Data
      were collected from 116 Dutch families with fathers, mothers and adolescents (10
      19 years old) included. Self-reports of these family members were used by means
      of questionnaires that were sent through the Internet. The findings showed that
      parents and adolescents differ in their reports on anti-smoking socialization. In
      general, mothers are more positive about anti-smoking socialization than
      adolescents and fathers. Furthermore, the results demonstrate that aspects of
      anti-smoking socialization, such as parental monitoring, norms on adolescents
      smoking and reactions on adolescent smoking, are related to smoking-related
      cognitions, such as negative attitudes to smoking, lower intentions to start
      smoking and higher self-efficacy. These findings are a first step in research on
      smoking-specific socialization that is considered to be of importance for the
      development of effective smoking prevention programmes focusing on parents.
      Nonetheless, longitudinal studies on large samples of families are needed to
      replicate the findings in this study.

PMID- 15140844
TI  - Contextualizing smoking: masculinity, femininity and class differences in smoking
      in men and women from three generations in the west of Scotland.
AB  - The epidemiology of smoking, and contemporary and historical accounts of tobacco
      consumption, together suggest that the patterning of smoking by class, gender and
      gender role identities may differ markedly for people born at different stages in
      the establishment and demise of smoking in the 20th century. Here, we report an
      analysis that examines this assertion using empirical data collected from men and
      women living in the west of Scotland, an area with high rates of smoking, who
      were born in the 1930s, 1950s and 1970s. Class trends in smoking were less
      apparent for men than for women in the older two cohorts and there was little
      evidence of class patterning in either sex in the youngest participants. There
      was little relationship between the measures of gender role orientation and
      current smoking amongst men. Amongst women, the strongest association was between
      smoking and a well-validated measure of 'femininity' in the 1950s cohort; each
      unit increase in 'femininity' score increased the odds of being a smoker by 46%.
      In this same cohort of women, there was also a weaker relationship between
      smoking and higher masculinity scores. These results are discussed in the context
      of continuing use of gendered imagery to exploit new markets in the developing
      world.

PMID- 15140845
TI  - Changing channels for tobacco control with youth: developing an intervention for
      working teens.
AB  - Worksites represent an untapped resource for reaching teens with tobacco control
      messages, given that 80% of teens have held at least one job by the time they
      graduate from high school. This paper presents formative research findings from a
      methods development study aimed at designing and testing a tobacco control
      intervention targeting working teens. Formative research included qualitative
      methods as well as quantitative data from a cross-sectional survey of teens
      employed in 10 participating grocery stores. Contrary to our a priori hypothesis,
      smoking rates among employed youth in this study were not higher than statewide
      averages and most of the teen workers were still in school, indicating that
      worksite interventions, at least in this setting, represent an alternative or
      adjunct to school-based programs, but do not necessarily capture a unique
      population. Employed teen tobacco use patterns and work characteristics that
      emerged from our formative research are presented in this paper, and may be
      useful in planning future worksite interventions for employed teens.

PMID- 15140846
TI  - Children's eating attitudes and behaviour: a study of the modelling and control
      theories of parental influence.
AB  - The present study compared the modelling and control theories of parental
      influence on children's eating attitudes and behaviour with a focus on snack
      foods. Matched questionnaires describing reported snack intake, eating
      motivations and body dissatisfaction were completed by 112 parent/child pairs.
      Parents completed additional items relating to control in terms of attempts to
      control their child's food intake and using food as a tool for controlling
      behaviour. The results showed significant correlations between parent and child
      for reported snack intake, eating motivations and body dissatisfaction,
      indicating an important role for modelling. Parents were then divided according
      to their control scores. Children whose parents indicated greater attempts to
      control their child's diets reported higher intakes of both healthy and unhealthy
      snack foods. In addition, those children whose parents indicated a greater use of
      food as a means to control their child's behaviour reported higher levels of body
      dissatisfaction. The results provide some support for both the modelling and
      control theories of parental influence. However, whereas modelling appears to
      have a consistent impact, parental control has a differential impact depending
      upon whether this control is focused on the child's diet or on other aspects of
      their behaviour. To conclude, a positive parental role model may be a better
      method for improving a child's diet than attempts at dietary control.

PMID- 15140847
TI  - Developing and testing measures predictive of hepatitis A vaccination in a sample
      of men who have sex with men.
AB  - Studies continue to show that the majority of men who have sex with men (MSM) in
      the US remain unvaccinated against the hepatitis A virus (HAV). Such limited
      vaccination coverage is a missed opportunity to prevent disease. This study was
      designed to develop reliable and valid theory-based quantitative measures to
      understand beliefs and attitudes regarding HAV vaccination among MSM. A
      convenience sample of 358 patrons of two gay bars in Birmingham, Alabama,
      completed a theory-based questionnaire. Data were randomly split into two groups.
      Exploratory factor analysis (EFA) was performed on the first split-half sample to
      identify factor structure using standard principal component analysis.
      Confirmatory factor analysis (CFA) was performed on the remaining half sample
      using structural equation modeling. EFA revealed five scales measuring beliefs
      about HAV vaccination, including: perceived barriers and benefits associated with
      HAV vaccination; perceived severity and susceptibility related to hepatitis A
      infection; and perceived self- efficacy to complete the two-dose vaccine series.
      CFA revealed acceptable absolute model fits for four scales and excellent
      comparative model fits for all five scales. Multivariable analysis further
      validated the scales. Although the results should be tested further, these
      findings propose standardized measures that may be useful in assessing the
      beliefs and attitudes of MSM towards HAV vaccination to guide intervention design
      and evaluation.

PMID- 15140848
TI  - A school-based survey of recurrent non-specific low-back pain prevalence and
      consequences in children.
AB  - The aim of this investigation was to provide evidence of the prevalence and
      consequences of recurrent low-back pain in children from Northwest England. A
      cross-sectional survey was conducted involving a standardized questionnaire with
      established reliability and validity. A cross-sectional sample of 500 boys (n =
      249) and girls (n = 251) aged between 10 and 16 years participated in the study.
      Average lifetime prevalence of low-back pain was 40.2% [95% confidence interval
      (CI) = 38.7-41.6]. Most cases of low-back pain were acute episodes that did not
      lead to disabling consequences. In contrast, 13.1% (95% CI = 12.5-13.7)
      experienced recurrent low-back pain that led to disabling consequences; 23.1%
      visited a medical practitioner, 30.8% experienced loss of physical
      activity/sports and 26.2% had been absent from school because of low-back pain.
      Recurrent low-back pain was particularly evident during late adolescence where
      one in five children were cases. The health education implications of low-back
      pain in children are discussed. It was concluded that low-back pain is a common
      complaint during childhood, although most cases are acute episodes that represent
      little health consequence. In contrast, some children experience recurrent low
      back pain that can lead to disabling consequences. Future research should focus
      on recurrent low-back pain cases since they often led to disabling consequences.

PMID- 15140849
TI  - The effectiveness of an interactive multimedia program to influence eating
      habits.
AB  - An interactive multimedia program to encourage individuals to decrease their
      dietary fat consumption and to increase consumption of fruits and vegetables was
      developed and evaluated at two worksites. The program presented content tailored
      to the user by gender, content interests, race, and age group. It was tested
      using a randomized treatment and wait list control design (n = 517). Repeated
      measures ANOVAs indicated significant intervention effects after 30 days for self
      reported consumption of fat and of fruits and vegetables, for stage of change to
      adopt a low-fat diet, for intention and self-efficacy to reduce dietary fat, and
      for attitude toward the importance of diet. In addition, 60-day follow-up of the
      treatment subjects found that program effects were maintained on all measures.
      Within- subject analyses showed that program effects were replicated with the
      wait list group at 30 days. These results demonstrate the potential for short
      exposure interactive programs to positively impact eating habits of employee
      populations.

PMID- 15140850
TI  - Case study of a healthy eating intervention for Swedish lorry drivers.
AB  - Professional drivers, i.e. lorry, truck, bus and taxi drivers, have been
      identified as a particular health risk group. An intervention to study the
      efficacy of a series of educational programmes, involving improved nutritional
      balance in meals served, food preparation routines and carrying out personal
      health profiles on staff, was implemented at a Swedish truck stop in order to
      target this specific hard-to-reach risk group. Professional drivers were targeted
      through an information campaign, healthier 'Today's Special' choices and by using
      staff as proxy health promoters. A campaign emblem on the menu notice board
      indicated healthier food choice menu items. Drivers choosing healthier
      alternatives were given lottery tokens. The intervention was evaluated through
      nutritional analyses, field observations, questionnaires and interviews. Positive
      staff-level outcomes included increased nutritional awareness, personal health
      empowerment and, most crucially, overwhelming staff support for a health
      promoting role. Nutritional analysis of pre- and post-intervention 'Today's
      Specials' showed a better balance of fat, calories, carbohydrates and protein
      (per 100 g) content in the dishes tested. At management level there were economic
      benefits in terms of time savings and reduced use of cooking fat in food
      preparation. Drivers tended to choose healthier alternatives and there was
      increased awareness of the healthier alternatives on offer. The case study showed
      that using truck stop staff as proxy health promoters offers a viable
      intervention strategy.

PMID- 15140851
TI  - An implementation study of two evidence-based exercise and health education
      programmes for older adults with osteoarthritis of the knee and hip.
AB  - Implementation studies are recommended to assess the feasibility and
      effectiveness in real-life of programmes which have been tested in randomized
      controlled trials (RCTs). We report on an implementation study of two evidence
      based exercise and health education programmes for older adults with
      osteoarthritis (OA) of the knee or hip. Three types of primary health-care
      providers (n = 18) delivered the OA Knee programme (n = 20) and the OA Hip
      programme (n = 20), supported by programme manuals and implementation guidelines,
      in four regions. The outcome measures were pain and mobility. The Knee programme
      had OA knowledge and self-efficacy as additional outcome measures. Differences in
      outcome measures and background variables of participants were assessed between
      the RCTs and the implementation study. Positive effects (P < 0.05) were found for
      OA knowledge, pain and self-efficacy in the Knee programme (n = 157), and for
      pain in the Hip programme (n = 132). No effect was found for mobility. Effect
      sizes of the RCTs and the present study were comparable. Background variables did
      not explain the variance in the outcome measures. The outcomes of the previous
      RCTs and the implementation study were comparable, and indicated the ecological
      validity of the two programmes. The implications for nationwide dissemination and
      implementation in The Netherlands are discussed.

PMID- 15140852
TI  - Changing concepts of health and illness among children of primary school age in
      Western Kenya.
AB  - This paper examines changes in children's concepts of health and illness
      following an action-oriented health education intervention in Bondo district of
      Western Kenya. The study is a feasibility study exploring a specific educational
      approach, and it combines elements of health education research and
      anthropological research. Forty primary schoolchildren aged 10-15 years of age
      underwent a 2-month intervention and were thereafter enrolled as health
      communicators in a longitudinal study for an additional period of 12 months. Data
      were collected before, during and after the intervention using in-depth
      interviews and the draw-and-write technique. Students' actions and their active
      participation were key elements in the intervention. Although the intervention
      from the beginning focused on two specific diseases (malaria and diarrhea), the
      students were involved in developing their own ideas and visions about which
      changes to make, which actions to carry out and which target groups to approach.
      Data showed that children had acquired new concepts of health, some of which
      incorporated elements of the old ones. More action-oriented health concepts were
      identified and a general change from an external locus of control towards an
      internal locus of control was found. The study concludes that students can modify
      and broaden their concepts of health and illness through action-oriented health
      education. Key factors are the development of students' ownership through active
      and participatory teaching and learning approaches.

PMID- 15140853
TI  - Critical health promotion and education--a new research challenge.
AB  - In relation to health promotion and education, the use of post-positivist and
      constructivist approaches has been gathering strength in recent years. Despite
      this emerging tradition, little has been done to explore what this sort of
      approach actually represents, particularly in terms of health promotion in
      schools, professional organizations and wider society. Acknowledging this, it is
      suggested that more researchers in this area should be adopting qualitative
      approaches-including semi-structured interviews, focus groups, story/dialogue
      workshops and developmental schemes of health education-in order to uncover the
      hidden meaning of 'health promotion', particularly in the school context. This
      paper therefore attempts to challenge the idea that traditionalist paradigms of
      positivist research are capable of appropriately representing the nature and
      complexity of the health promotion issues. In this paper, methodological and
      theoretical frameworks that can enable researchers to understand health promotion
      from the perspective of students, teachers and school 'stakeholders' are
      suggested. Particular attention is given to a discussion of the potential value
      of designing and implementing programmes of health education or promotion using a
      critical pedagogical approach within schools in the UK. It is argued that
      programmes using a critical pedagogical and reflective approach, and which are
      aimed at social transformation, would be of enormous benefit to both researchers
      and educational/health professionals who are seeking to understand the complexity
      of health promotion issues from the perspective of children and adolescents.

PMID- 15140855
TI  - Plasmid-encoded functions compensate for the biological cost of AmpC
      overexpression in a clinical isolate of Salmonella typhimurium.
AB  - OBJECTIVES: In a previous study with a Salmonella typhimurium strain containing
      cloned ampC-ampR from Enterobacter cloacae, it was suggested that ampC expression
      must be kept at low levels by AmpR to maintain normal growth and virulent
      phenotype. The purpose of this study was to determine whether findings obtained
      with a laboratory model can be extended to a virulent clinical isolate of S.
      typhimurium expressing the plasmid-encoded bla(CMY-7). METHODS: Disc induction
      assays were carried out to investigate inducibility of bla(CMY-7). Primer
      extension and sequence analyses were carried out to map the transcriptional start
      site of bla(CMY-7) and determine the relative expression. Growth and invasion
      potential of Salmonella strains were monitored by optical density, viable counts
      and cell invasion assays. RESULTS: Sequence analysis confirmed the absence of
      ampR upstream of bla(CMY-7) therefore confirming the negative results observed
      using the disc induction assay. Primer extension analysis mapped the start site
      of bla(CMY-7) transcription within an ISEcp1-like element. The relative
      expression of bla(CMY-7) was approximately 965-fold higher than the expression of
      a wild-type Citrobacter freundii chromosomal ampC and approximately 4.1-fold
      higher than ampC expression from a derepressed mutant of C. freundii. Growth and
      the capacity to invade mammalian cells were not compromised for either the
      clinical isolate or the S. typhimurium transconjugant containing bla(CMY-7).
      However, a Salmonella transformant containing bla(CMY-7) exhibited a compromised
      phenotype with respect to growth and invasion of mammalian cells. CONCLUSION:
      These findings indicate that the biological cost of high-level AmpC production
      can be compensated by plasmid-encoded factors and not by regulating ampC
      expression.

PMID- 15140856
TI  - Antifungal effects of Melaleuca alternifolia (tea tree) oil and its components on
      Candida albicans, Candida glabrata and Saccharomyces cerevisiae.
AB  - OBJECTIVES: The aim of this study was to investigate the mechanism of action of
      tea tree oil and its components against Candida albicans, Candida glabrata and
      Saccharomyces cerevisiae. METHODS: Yeast cells were treated with tea tree oil or
      components, at one or more concentrations, for up to 6 h. During this time,
      alterations in permeability were assessed by measuring the leakage of 260 nm
      absorbing materials and by the uptake of Methylene Blue dye. Membrane fluidity
      was measured by 1,6-diphenyl-1,3,5-hexatriene fluorescence. The effects of tea
      tree oil on glucose-induced medium acidification were quantified by measuring the
      pH of cell suspensions in the presence of both tea tree oil and glucose. RESULTS:
      The treatment of C. albicans with tea tree oil and components at concentrations
      of between 0.25 and 1.0% (v/v) altered both permeability and membrane fluidity.
      Membrane fluidity was also increased when C. albicans was cultured for 24 h with
      0.016%-0.06% (v/v) tea tree oil, as compared with control cells. For all three
      organisms, glucose-induced acidification of the external medium was inhibited in
      a dose-dependent manner in the presence of 0.2%, 0.3% and 0.4% tea tree oil.
      CONCLUSIONS: Data from this study support the hypothesis that tea tree oil and
      components exert their antifungal actions by altering membrane properties and
      compromising membrane-associated functions.

PMID- 15140857
TI  - Pharmacokinetics of valaciclovir.
AB  - While active against Herpesviridae, oral aciclovir is limited by low and
      inconsistent bioavailability. Modification of aciclovir by valine esterification,
      producing valaciclovir, results in significant increases in systemic aciclovir
      plasma levels. The exact mechanism of increased absorption with valaciclovir is
      not fully determined but probably involves intestinal dipeptide transporters,
      followed by rapid ester hydrolysis in the small intestine and liver. The enhanced
      pharmacokinetics of valaciclovir have translated into improvements in clinical
      efficacy and patient convenience.

PMID- 15140858
TI  - Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in
      Austria.
AB  - OBJECTIVES: To determine the prevalence of antibiotic resistance and the
      distribution of serotypes among Streptococcus pneumoniae isolated in Austria.
      MATERIALS AND METHODS: A total of 2367 strains of S. pneumoniae were collected in
      an Austrian-wide surveillance system between 1996 and 2002. Isolates were tested
      for their susceptibility to penicillin and clarithromycin and were serotyped by
      the capsular swelling method. RESULTS: An overall rise in penicillin resistance
      was observed from 4.9% in 1996 to 10.0% in 2002 (including both intermediate
      resistant and resistant strains). A rise in clarithromycin resistance was also
      recorded in this period. The overall distribution of serogroups/types remained
      relatively stable, with 23, 19, 6 and 14 being the most frequent ones. Whereas in
      1996 penicillin resistance was predominantly associated with serotype 23F, in
      1998 and 2002, resistance was most frequently found in isolates of serogroup 9
      and serotype 14, respectively. Coverage rates for currently available vaccines
      ranged from 57.4% (7-valent) to 72.4% (23-valent) of all serotyped strains.
      CONCLUSIONS: This rise in pneumococcal resistance to penicillin and
      clarithromycin, and the change in distribution of serotypes in these resistant
      strains, indicates that ongoing surveillance programmes are warranted, in order
      to be able to formulate both effective vaccination strategies and optimal
      antibiotic therapies.

PMID- 15140859
TI  - Serotonin syndrome due to co-administration of linezolid and venlafaxine.

PMID- 15140861
TI  - CDC studies incorrectly summarized in 'critical review'.

PMID- 15140862
TI  - Does the use of antibiotics in food animals pose a risk to human health? An
      unbiased review?

PMID- 15140863
TI  - Comment on: Does the use of antibiotics in food animals pose a risk to human
      health? A critical review of published data.

PMID- 15140864
TI  - Antibiotic growth promoters.

PMID- 15140865
TI  - Factual errors in review article.

PMID- 15140866
TI  - Germline stem cells in the postnatal ovary: is the ovary more like a testis?

PMID- 15140867
TI  - Experimental approaches to the study of primordial germ cell lineage and
      proliferation.
AB  - New information regarding primordial germ cell (PGC's) segregation and
      proliferation over the last decade is reviewed. Advances have been obtained in
      the mouse but current knowledge of human PGC's remains scant. Questions still
      fully or partially unresolved about the emergence of the germline in mammals are
      addressed. (i) When and where is the germ line set aside in the embryo? (ii) How
      is the germ line segregated from the somatic lineages? (iii) Which factors guide
      PGC's to the gonadal ridges? (iv) Which factors regulate PGC's proliferation? The
      main purpose of this review is to outline the information obtained using mainly
      in vitro culture systems about two aspects of these processes namely the
      segregation of PGC's and their proliferation.

PMID- 15140868
TI  - Sex steroidal regulation of uterine leiomyoma growth and apoptosis.
AB  - Uterine leiomyomas develop during the reproductive years and regress after
      menopause, indicating ovarian steroid-dependent growth potential. Although the
      clinical and biochemical observations have traditionally supported an important
      role for estrogen in the promotion of leiomyoma growth, there is also increasing
      evidence to suggest the involvement of progesterone in the pathogenesis of
      leiomyoma. In this review, much attention has been paid to characterizing the
      molecular mechanisms of sex steroidal regulation of leiomyoma growth and
      apoptosis by evaluating the effects of sex steroids on the expression of growth
      factors and apoptosis-related factors. The effects of GnRH agonist on the
      expression of these factors in leiomyoma are also described. 17beta-Estradiol up
      regulates epidermal growth factor (EGF) receptor, but down-regulates p53 protein
      in leiomyoma cells, whereas progesterone augments EGF and Bcl-2 protein, but
      inhibits insulin-like growth factor (IGF-I) and tumour necrosis factor
      (TNFalpha). Since it is now evident that EGF and IGF-I act as local factors which
      stimulate leiomyoma growth, these findings suggest that progesterone may have
      dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival,
      depending on the local growth factor conditions around each leiomyoma. This may
      explain why the size of uterine leiomyomas during the use of levonorgestrel
      releasing intrauterine system (LNG-IUS) increases in some but decreases in other
      instances. This may also explain why the size of leiomyomas during pregnancy does
      not increase despite the overwhelming increase in circulating concentrations of
      sex steroid hormones. Moreover, there is further evidence to suggest that the
      interactions between estrogen receptors and progesterone receptors may be
      involved in the modulation of gene transcription activity in leiomyoma. This
      review demonstrates that leiomyoma growth is integrally regulated by the complex
      cross-talk between sex steroid hormones and growth factors.

PMID- 15140869
TI  - A cytogeneticist's perspective on genomic microarrays.
AB  - The identification of cytogenetic imbalance is an important component of clinical
      genetics. About 1 in 154 newborns has a chromosome abnormality. Conventional
      cytogenetic analysis has enabled the identification of microscopic alterations of
      the chromosomes. The development of fluorescence in situ hybridization (FISH) and
      other molecular methodologies has made possible the identification of
      submicroscopic aberrations. An additional development was comparative genomic
      hybridization (CGH), a method that directly compares two genomes for DNA copy
      differences. As first developed, the substrate for CGH analysis is normal
      metaphase chromosomes. Recently, CGH has been applied to microarrays (array CGH)
      constructed from large insert clones to identify chromosome imbalance. Array CGH
      has many advantages over conventional cytogenetic and molecular cytogenetic
      techniques. Array CGH can be comprehensive (genome-wide), high resolution,
      amenable to automation, rapid, and sensitive. We anticipate that array CGH will
      be employed in the clinical cytogenetics laboratory in the near future and will
      lead to the identification of the chromosomal basis of new syndromes and existing
      genetic conditions.

PMID- 15140870
TI  - Characterization of the ovarian transcriptome through the use of differential
      analysis of gene expression methodologies.
AB  - Prior to the development of high-throughput methods for the analysis of
      differential gene expression, genes required for proper ovarian function were
      identified on a case-by-case basis. Recently, however, several techniques have
      been developed that enable investigators to study large-scale changes in gene
      expression under a variety of experimental conditions. The utilization of these
      methodologies has led to the identification of a number of novel or previously
      unappreciated genes that are expressed within distinct cell types in the ovary or
      at specific stages of the ovarian cycle. This review details the recent use of
      differential analysis strategies in identifying (i) genes that are expressed
      exclusively or preferentially in the ovary, (ii) genes that are differentially
      expressed in isolated ovarian cells in response to hormonal stimulation, and
      (iii) those genes that are expressed at specific stages of the ovarian cycle. The
      genes identified through the use of these approaches represent potential targets
      for designing agents capable of regulating ovarian physiology and thus fertility.

PMID- 15140871
TI  - Cytoplasmic transfer in oocytes: biochemical aspects.
AB  - Cytoplasmic control of preimplantation development is not a 'new' concept; the
      first cytoplasmic transfer experiment was performed in the mouse during the early
      1980s, as a means of overcoming cleavage arrest at the 2-cell stage, the '2-cell
      block'. Since the first human pregnancy following the transfer of cytoplasm from
      donor oocytes into the oocytes of a patient with a history of poor embryo
      development and recurrent implantation failure in 1997, >30 children have been
      born after direct injection of ooplasm from fresh, mature or immature, or
      cryopreserved-thawed donor oocytes into recipient oocytes via a modified ICSI
      technique. Transfer of ooplasm was thus applied with astonishing speed in humans,
      in the absence of extensive research to evaluate the efficacy and the possible
      risks of the method. This review focuses on biochemical mechanisms by which
      transfer of ooplasm might confer a benefit: by correcting a putative imbalance
      between anti- and pro-apoptotic factors and/or correction of defective
      mitochondrial membrane potential. We also emphasize the 'empirical' state of this
      technique, and the related risks.

PMID- 15140872
TI  - Fertility preservation in female patients.
AB  - In the USA alone, >650 000 women will be afflicted by cancer in 2003, and 8% of
      these cases will be aged <40 years. Due to improvements in cancer therapy, cure
      rates of both adult and childhood cancers increased significantly over the past
      three decades. However, long-term consequences of cancer therapy and impact on
      quality of life are now being recognized. One of the major sequelae of cytotoxic
      chemotherapy is gonadal failure. Cytotoxic chemotherapy and/or radiotherapy are
      not only used to treat malignant diseases, but also non-malignant systemic
      conditions. Upon reviewing the extent and mechanism of gonadal damage due to
      chemo-/radiotherapy, this article discusses indications and the wide range of
      methods of fertility preservation in a comprehensive manner. All current,
      emerging, experimental as well as controversial approaches are reviewed. A
      comprehensive algorithm to manage fertility preservation through an
      individualized approach is presented.

PMID- 15140873
TI  - Improving reproductive performance in overweight/obese women with effective
      weight management.
AB  - Obesity and overweight are common conditions in the developed countries and they
      carry many health consequences, including some reproductive disorders. There is a
      very high prevalence of obese women in the infertile population and many studies
      have highlighted the link between obesity and infertility. A large proportion of
      infertile women have polycystic ovary syndrome (PCOS) which is also linked with
      increased risk of obesity and other metabolic anomalies. The association between
      obesity and/or PCOS and hyperinsulinaemia, hyper androgenism and abnormal
      secretion of other hormones, such as leptin, underlies many reproductive
      disorders observed in this population. It has been demonstrated that weight loss
      can improve the fertility of obese women through the recovery of spontaneous
      ovulation, whereas others will have improved response to ovarian stimulation in
      infertility treatment. Therefore, it is proposed that following the initial
      assessment of infertility and body mass index or other measurement of obesity,
      various weight management interventions, including diet, exercise or
      pharmacotherapeutic approaches, should be considered for overweight and obese
      infertile women.

PMID- 15140874
TI  - The M3 receptor-mediated K(+) current (IKM3), a G(q) protein-coupled K(+)
      channel.
AB  - Stimulation of muscarinic acetylcholine receptors (mAChRs) can activate an inward
      rectifier K(+) current (I(KACh)), which is mediated by the M(2) subtype of mAChR
      in cardiac myocytes. Recently, a novel delayed rectifier-like K(+) current
      mediated by activation of the cardiac M(3) receptors (designated I(KM3)) was
      identified, which is distinct from I(KACh) and other known K(+) currents. While
      I(KACh) is known to be a G(i) protein-gated K(+) channel, the signal transduction
      mechanisms for I(KM3) activation remained unexplored. We studied I(KM3) with
      whole-cell patch clamp and macropatch clamp techniques. Whole cell I(KM3)
      activated by choline persisted with minimal rundown over 2 h in presence of
      internal GTP. When GTP was replaced by guanyl-5'-yl thiophosphate, I(KM3)
      demonstrated rapid and extensive rundown. While I(KACh) (induced by ACh) was
      markedly reduced in cells pretreated with pertussis toxin, I(KM3) was unaltered.
      Intracellular application of antibodies targeting alpha-subunit of G(i/o) protein
      suppressed I(KACh) without affecting I(KM3). Antibodies targeting the N and the C
      terminus, respectively, of G(q) protein alpha-subunit substantially depressed
      I(KM3) but failed to alter I(KACh). The antibody against beta-subunits of G
      proteins inhibited both I(KACh) and I(KM3). I(KM3) activated by choline in the
      cell-attached mode of macropatches persisted in the cell-free configuration.
      Application of purified G(q) protein alpha-subunit or betagamma-subunit of G
      proteins or guanosine 5'-O-(thiotriphosphate) to the internal solution activated
      I(KM3)-like currents in inside-out patches. Our findings revealed a novel aspect
      of receptor-channel signal transduction mechanisms, and I(KM3) represents the
      first G(q) protein-coupled K(+) channel. We propose that the G protein-coupled
      K(+) channel family could be divided into two subfamilies: G(i) protein-coupled
      K(+) channel subfamily and G(q) protein-coupled K(+) channel subfamily.

PMID- 15140875
TI  - Hepatoma-derived growth factor is a neurotrophic factor harbored in the nucleus.
AB  - Hepatoma-derived growth factor (HDGF) is a heparin-binding proliferating factor
      originally isolated from conditioned medium of the hepatoma-derived cell line HuH
      7. HDGF has greatest homology in an amino acid sequence with high mobility group
      1 (HMG1), which has been characterized as a DNA-binding, inflammatory, and potent
      neurite outgrowth molecule. HDGF is reported to be widely expressed and act as a
      growth factor in many kinds of cells. However, it has not been investigated in
      the nervous system. Here, we show by Western blot analysis that HDGF is present
      in the mouse brain from the embryonic period until adulthood. In situ
      hybridization and immunohistochemical analyses revealed that HDGF was expressed
      mainly in neurons, and HDGF protein was localized to the nucleus. HDGF and high
      mobility group 1 were secreted under physiological conditions and released
      extracellularly in necrotic conditions. Furthermore, we showed that exogenously
      supplied HDGF had a neurotrophic effect and was able to partially prevent the
      cell death of neurons in which endogenous HDGF was suppressed. Therefore, we
      propose that HDGF is a novel type of neurotrophic factor, on account of its
      localization in the nucleus and its potential to function in an autocrine manner
      under both physiological and pathological conditions throughout life.

PMID- 15140877
TI  - Structural determinants of substrate binding to Bacillus cereus metallo-beta
      lactamase.
AB  - Binding and hydrolysis of the beta-lactams cefotaxime, cephapirin, imipenem, and
      benzylpenicillin by the metallo-beta-lactamase from Bacillus cereus were studied
      by presteady state kinetic measurements. In all cases, the substrate was
      unmodified in the most populated reaction intermediate, and no chemically
      modified substrate species accumulated to a detectable amount. The cephalosporins
      tested showed similar formation rate constants for this intermediate, and they
      differed mostly in their decay rates. Formation of a non-productive
      enzyme.substrate complex was detected for imipenem. The substrate binding
      differences can be accounted for by considering the structural features of each
      substrate. The apoenzyme could not bind any of the substrates, but binding was
      restored when the apoenzyme was reconstituted with Zn(II), revealing that the
      metal ions are the main determinants of substrate binding. This evidence is in
      line with the lack of an optimized substrate recognition patch in B1 and B3
      metallo-beta-lactamases that provides a broad substrate spectrum.

PMID- 15140876
TI  - Structure and function of extracellular loop 4 of the serotonin transporter as
      revealed by cysteine-scanning mutagenesis.
AB  - Residues 386-423 of the rat brain serotonin transporter (SERT) are predicted to
      form a hydrophilic loop connecting transmembrane spans 7 and 8 (extracellular
      loop 4 or EL4). EL4 has been hypothesized to play a role in conformational
      changes associated with substrate translocation. To more fully investigate EL4
      structure and function, we performed cysteine-scanning mutagenesis and
      methanethiosulfonate (MTS) accessibility studies on these 38 residues. Four EL4
      mutants (M386C, R390C, G402C, and L405C) showed very low transport activities,
      low cell surface expression, and strong inhibition by MTS reagents, indicating
      high structural and functional importance. Twelve mutants were sensitive to very
      low MTS concentrations, indicating positions highly exposed to the aqueous
      environment. Eleven mutants were MTS-insensitive, indicating positions that were
      either buried in EL4 structure or functionally unimportant. The patterns of
      sensitivity to mutation and MTS reagents were used to produce a structural model
      of EL4. Positions 386-399 and 409-421 are proposed to form alpha-helices,
      connected by nine consecutive MTS-sensitive positions, within which four
      positions, 402-405, may form a turn or hinge. The presence of serotonin changed
      the MTS accessibility of cysteines at nine positions, while cocaine, a non
      transportable blocker, did not affect accessibility. Serotonin-induced
      accessibility changes required both Na(+) and Cl(-), indicating that they were
      associated with active substrate translocation. With the exception of a single
      mutant, F407C, neither mutation to cysteine nor treatment with MTS reagents
      affected SERT affinities for serotonin or the cocaine analog beta-CIT. These
      studies support the role of EL4 in conformational changes occurring during
      translocation and show that it does not play a direct role in serotonin binding.

PMID- 15140878
TI  - Transcriptional regulation by the repressor of estrogen receptor activity via
      recruitment of histone deacetylases.
AB  - Histone acetyltransferases and deacetylases are recruited by transcription
      factors and adapter proteins to regulate specific subsets of target genes. We
      were interested in identifying interaction partners of histone deacetylase 1
      (HDAC1) that might be involved in conferring target or substrate specificity.
      Using the yeast two-hybrid system, we isolated the repressor of estrogen receptor
      activity (REA) as a novel HDAC1-associated protein. We demonstrated the in vivo
      interaction of REA with HDAC1 and characterized the respective domains required
      for their interaction in vitro. In addition, we found that REA also associates
      with the class II histone deacetylase HDAC5. In luciferase reporter assays, REA
      decreased transcription, and this repression was sensitive to the deacetylase
      inhibitor trichostatin A. Finally, we showed that REA specifically interacts with
      the chicken ovalbumin upstream binding transcription factors and II. The nuclear
      receptor chicken ovalbumin upstream binding transcription factor I was found to
      cooperate with REA and histone deacetylases in the repression of target genes.
      We, therefore, propose a novel function for REA as a mediator of transcriptional
      repression by nuclear hormone receptors via recruitment of histone deacetylases.

PMID- 15140879
TI  - Regulation of the multifunctional Ca2+/calmodulin-dependent protein kinase II by
      the PP2C phosphatase PPM1F in fibroblasts.
AB  - The regulation of the multifunctional calcium/calmodulin dependent protein kinase
      II (CaMKII) by serine/threonine protein phosphatases has been extensively studied
      in neuronal cells; however, this regulation has not been investigated previously
      in fibroblasts. We cloned a cDNA from SV40-transformed human fibroblasts that
      shares 80% homology to a rat calcium/calmodulin-dependent protein kinase
      phosphatase that encodes a PPM1F protein. By using extracts from transfected
      cells, PPM1F, but not a mutant (R326A) in the conserved catalytic domain, was
      found to dephosphorylate in vitro a peptide corresponding to the auto-inhibitory
      region of CaMKII. Further analyses demonstrated that PPM1F specifically
      dephosphorylates the phospho-Thr-286 in autophosphorylated CaMKII substrate and
      thus deactivates the CaMKII in vitro. Coimmunoprecipitation of CaMKII with PPM1F
      indicates that the two proteins can interact intracellularly. Binding of PPM1F to
      CaMKII involves multiple regions and is not dependent on intact phosphatase
      activity. Furthermore, overexpression of PPM1F in fibroblasts caused a reduction
      in the CaMKII-specific phosphorylation of the known substrate vimentin(Ser-82)
      following induction of the endogenous CaM kinase. These results identify PPM1F as
      a CaM kinase phosphatase within fibroblasts, although it may have additional
      functions intracellularly since it has been presented elsewhere as POPX2 and hFEM
      2. We conclude that PPM1F, possibly together with the other previously described
      protein phosphatases PP1 and PP2A, can regulate the activity of CaMKII. Moreover,
      because PPM1F dephosphorylates the critical autophosphorylation site of CaMKII,
      we propose that this phosphatase plays a key role in the regulation of the kinase
      intracellularly.

PMID- 15140880
TI  - Zebrafish reveals different and conserved features of vertebrate neuroglobin gene
      structure, expression pattern, and ligand binding.
AB  - Neuroglobin has been identified as a respiratory protein that is primarily
      expressed in the mammalian nervous system. Here we present the first detailed
      analysis of neuroglobin from a non-mammalian vertebrate, the zebrafish Danio
      rerio. The zebrafish neuroglobin gene reveals a mammalian-type exon-intron
      pattern in the coding region (B12.2, E11.0, and G7.0), plus an additional 5'-non
      coding exon. Similar to the mammalian neuroglobin, the zebrafish protein displays
      a hexacoordinate deoxy-binding scheme. Flash photolysis kinetics show the
      competitive binding on the millisecond timescale of external ligands and the
      distal histidine, resulting in an oxygen affinity of 1 torr. Western blotting,
      immune staining, and mRNA in situ hybridization demonstrate neuroglobin
      expression in the fish central nervous system and the retina but also in the
      gills. Neurons containing neuroglobin have a widespread distribution in the brain
      but are also present in the olfactory system. In the fish retina, neuroglobin is
      mainly present in the inner segments of the photoreceptor cells. In the gills,
      the chloride cells were identified to express neuroglobin. Neuroglobin appears to
      be associated with mitochondria-rich cell types and thus oxygen consumption
      rates, suggesting a myoglobin-like function of this protein in facilitated oxygen
      diffusion.

PMID- 15140882
TI  - Induction of p100 processing by NF-kappaB-inducing kinase involves docking
      IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation.
AB  - The processing of the nfkappab2 gene product p100 to generate p52 is a regulated
      event, which is important for the instrumental function of NF-kappaB. We
      previously demonstrated that this tightly controlled event is regulated
      positively by NF-kappaB-inducing kinase (NIK) and its downstream kinase, IkappaB
      kinase alpha (IKKalpha). However, the precise mechanisms by which NIK and
      IKKalpha induce p100 processing remain unclear. Here, we show that, besides
      activating IKKalpha, NIK also serves as a docking molecule recruiting IKKalpha to
      p100. This novel function of NIK requires two specific amino acid residues,
      serine 866 and serine 870, of p100 that are known to be essential for inducible
      processing of p100. We also show that, after being recruited into p100 complex,
      activated IKKalpha phosphorylates specific serines located in both N- and C
      terminal regions of p100 (serines 99, 108, 115, 123, and 872). The
      phosphorylation of these specific serines is the prerequisite for ubiquitination
      and subsequent processing of p100 mediated by the beta-TrCP ubiquitin ligase and
      26 S proteasome, respectively. These results highlight the critical but different
      roles of NIK and IKKalpha in regulating p100 processing and shed light on the
      mechanisms mediating the tight control of p100 processing. These data also
      provide the first evidence for explaining why overexpression of IKKalpha or its
      activation by many other stimuli such as tumor necrosis factor and mitogens fails
      to induce p100 processing.

PMID- 15140881
TI  - Tight junction protein Par6 interacts with an evolutionarily conserved region in
      the amino terminus of PALS1/stardust.
AB  - Tight junctions are the structures in mammalian epithelial cells that separate
      the apical and basolateral membranes and may also be important in the
      establishment of cell polarity. Two evolutionarily conserved multiprotein
      complexes, Crumbs-PALS1 (Stardust)-PATJ and Cdc42-Par6-Par3-atypical protein
      kinase C, have been implicated in the assembly of tight junctions and in
      polarization of Drosophila melanogaster epithelia. These two complexes have been
      linked physically and functionally by an interaction between PALS1 and Par6. Here
      we identify an evolutionarily conserved region in the amino terminus of PALS1 as
      the Par6 binding site and identify valine and aspartic acid residues in this
      region as essential for interacting with the PDZ domain of Par6. We have also
      characterized, in more detail, the amino terminus of Drosophila Stardust and
      demonstrate that the interaction mechanism between Stardust and Drosophila Par6
      is evolutionarily conserved. Par6 interferes with PATJ in binding PALS1, and
      these two interactions do not appear to function synergistically. Taken together,
      these results define the molecular mechanisms linking two conserved polarity
      complexes.

PMID- 15140883
TI  - Thermotoga maritima-Escherichia coli chimeric topoisomerases. Answers about
      involvement of the carboxyl-terminal domain in DNA topoisomerase I-mediated
      catalysis.
AB  - Bacterial topoisomerases I are generally composed of two domains as follows: a
      core domain, which contains all the conserved motifs involved in the trans
      esterification reactions, and a carboxyl-terminal domain, highly variable in size
      and sequence. In the present work, we have addressed the question of the
      respective roles of the two domains in the different steps of the
      topoisomerization cycle. For this purpose, we prepared various recombinant
      topoisomerases from two model enzymes: topoisomerase I from the hyperthermophilic
      bacterium Thermotoga maritima and topoisomerase I from Escherichia coli. We
      compared the properties of the two core domains to that of the topoisomerases
      formed by combining the core domain of one enzyme to the carboxyl-terminal domain
      of the other. We found that, contrary to E. coli (Lima, C. D., Wang, J. C., and
      Mondragon, A. (1993) J. Mol. Biol. 232, 1213-1216), the core domain from T.
      maritima (TmTop65) is able to sustain by itself a complete topoisomerization
      cycle, although with low efficiency. Fusion of TmTop65 to the entire carboxyl
      terminal domain from E. coli considerably increases binding efficiency, thermal
      stability, and DNA relaxation activity. Moreover, the chimera predominantly
      acquires the cleavage specificity of E. coli full-length topoisomerase. For the
      chimera obtained by fusion of the T. maritima carboxyl-terminal domain to the
      core EcTop67, very low DNA relaxation activity and binding are recovered, but
      formation of a covalent DNA adduct is impaired. Taken together, our results show
      that the presence and the nature of the carboxyl-terminal domain of bacterial
      topoisomerases I strongly determine their DNA binding efficiency and cleavage
      specificity but is not strictly required for strand passage.

PMID- 15140884
TI  - PIAS3 suppresses NF-kappaB-mediated transcription by interacting with the
      p65/RelA subunit.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor critical for key
      cellular processes, including immune response, apoptosis, and cell cycle
      progression. A yeast two-hybrid screening, using the Rel homology domain (RHD) of
      the p65 subunit (RelA) of NF-kappaB as bait, led to the isolation of PIAS3,
      previously identified as a specific inhibitor of STAT3. We show that PIAS3 can
      directly associate with p65 using an in vitro pull-down and in vivo
      coimmunoprecipitation assays. When overexpressed, PIAS3 inhibits NF-kappaB
      dependent transcription induced by treatment with tumor necrosis factor alpha
      (TNF-alpha) or interleukin-1beta or by overexpression of TNF family receptors
      such as RANK, TNFR1, and CD30 or signal transducers of TNF receptor-associated
      factors (TRAFs), including TRAF2, TRAF5, and TRAF6. Downregulation of PIAS3 by
      RNA interference reverses its effect on TNF-alpha-mediated NF-kappaB activation.
      We found that an N-terminal region of PIAS3 is necessary for both the interaction
      with p65 and the transcriptional suppression activity. In addition, we found that
      an LXXLL coregulator signature motif located within the N-terminal region of
      PIAS3 is the minimal requirement for the interaction with p65. Furthermore, we
      demonstrate that PIAS3 interferes with p65 binding to the CBP coactivator,
      thereby resulting in a decreased NF-kappaB-dependent transcription. Taken
      together, these data suggest that PIAS3 may function in vivo as a modulator in
      suppressing the transcriptional activity of p65.

PMID- 15140885
TI  - Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii.
AB  - We have exploited a variety of molecular genetic, biochemical, and genomic
      techniques to investigate the roles of purine salvage enzymes in the protozoan
      parasite Toxoplasma gondii. The ability to generate defined genetic knockouts and
      target transgenes to specific loci demonstrates that T. gondii uses two (and only
      two) pathways for purine salvage, defined by the enzymes hypoxanthine-xanthine
      guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK). Both HXGPRT
      and AK are single-copy genes, and either one can be deleted, indicating that
      either one of these pathways is sufficient to meet parasite purine requirements.
      Fitness defects suggest both pathways are important for the parasite, however,
      and that the salvage of adenosine is more important than salvage of hypoxanthine
      and other purine nucleobases. HXGPRT and AK cannot be deleted simultaneously
      unless one of these enzymes is provided in trans, indicating that alternative
      routes of functionally significant purine salvage are lacking. Despite previous
      reports to the contrary, we found no evidence of adenine
      phosphoribosyltransferase (APRT) activity when parasites were propagated in APRT
      deficient host cells, and no APRT ortholog is evident in the T. gondii genome.
      Expression of Leishmania donovani APRT in transgenic T. gondii parasites yielded
      low levels of activity but did not permit genetic deletion of both HXGPRT and AK.
      A detailed comparative genomic study of the purine salvage pathway in various
      apicomplexan species highlights important differences among these parasites.

PMID- 15140886
TI  - Selective and efficient immunoprecipitation of the disease-associated form of the
      prion protein can be mediated by nonspecific interactions between monoclonal
      antibodies and scrapie-associated fibrils.
AB  - Transmissible spongiform encephalopathies are characterized by the accumulation
      in brain tissues of an abnormal isoform of the prion protein named PrPsc, which
      is the only direct marker known for transmissible spongiform encephalopathies.
      Here we show that PrPsc can be specifically immunoprecipitated by using several
      monoclonal antibodies (mAbs) of various specificities independently of the
      properties of their binding site (paratope). These results strongly suggest that
      a significant proportion of mAbs can interact with PrPsc aggregates through
      nonspecific paratope-independent interactions allowing selective
      immunoprecipitation of PrPsc when these mAbs are immobilized on a polydisperse
      solid phase like microbeads.

PMID- 15140887
TI  - Crystal structure of the C-terminal peptidoglycan-binding domain of human
      peptidoglycan recognition protein Ialpha.
AB  - Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of
      the innate immune system that bind, and in some cases hydrolyze, peptidoglycans
      (PGNs) on bacterial cell walls. These molecules, which are highly conserved from
      insects to mammals, participate in host defense against both Gram-positive and
      Gram-negative bacteria. We report the crystal structure of the C-terminal PGN
      binding domain of human PGRP-Ialpha in two oligomeric states, monomer and dimer,
      to resolutions of 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN
      lytic amidase activity, no zinc ion is present in the PGN-binding site of human
      PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive topological
      variability in a large hydrophobic groove, located opposite the PGN-binding site,
      which may recognize host effector proteins or microbial ligands other than PGN.
      We also show that full-length PGRP-Ialpha comprises two tandem PGN-binding
      domains. These domains differ at most potential PGN-contacting positions,
      implying different fine specificities. Dimerization of PGRP-Ialpha, which occurs
      through three-dimensional domain swapping, is mediated by specific binding of
      sodium ions to a flexible hinge loop, stabilizing the conformation found in the
      dimer. We further demonstrate sodium-dependent dimerization of PGRP-Ialpha in
      solution, suggesting a possible mechanism for modulating PGRP activity through
      the formation of multivalent adducts.

PMID- 15140888
TI  - A structural requirement for processing the cardiac K+ channel KCNQ1.
AB  - Normal membrane protein function requires trafficking from the endoplasmic
      reticulum. Here, we studied processing of the KCNQ1 channel mutated in LQT1, the
      commonest form of the long QT syndrome. Serial C terminus truncations identified
      a small region (amino acids (aa) 610-620) required for normal cell surface
      expression. Non-trafficked truncations assembled as tetramers but were
      nevertheless retained in the endoplasmic reticulum. Further mutagenesis did not
      identify specific residues mediating channel processing; cell surface expression
      was preserved with the mutation of known trafficking motifs in the channel and
      with alanine scanning across aa 610-620. Structural prediction algorithms place
      aa 610-620 at the C-terminal end of an alpha-helix (aa 586-618) that includes a
      leucine zipper and is part of a coiled coil. Mutants disrupting the leucine
      zipper but preserving the predicted coiled coil reached the cell surface, whereas
      those disrupting the coil did not. These data suggest that specific protein
      protein interactions are required for normal channel processing. Further
      biochemical studies ruled out three candidate proteins, namely KCNE1, yotiao, and
      KCNQ1 itself, as effectors of this coiled coil-mediated trafficking. Four LQT1
      mutations within this helix generated little or no current and were not expressed
      on the cell surface, whereas LQT1 mutations in adjacent residues, which produce a
      milder clinical phenotype, generate only slightly reduced current and are
      expressed on the cell surface. These data suggest that mutations within this
      domain cause human disease by interfering with normal channel processing. More
      generally, we have identified a domain whose structural integrity is required for
      normal surface expression of the KCNQ1 channel.

PMID- 15140889
TI  - Probucol inactivates ABCA1 in the plasma membrane with respect to its mediation
      of apolipoprotein binding and high density lipoprotein assembly and to its
      proteolytic degradation.
AB  - Probucol has been shown to inhibit the release of cellular lipid by helical
      apolipoprotein and thereby to reduce plasma high density lipoprotein. We
      attempted to explore the underlying mechanism for this effect in human fibroblast
      WI-38. Probucol inhibited the apoA-I-mediated cellular lipid release and binding
      of apoA-I to the cells in a dose-dependent manner. It did not influence cellular
      uptake of low density lipoprotein, transport of cholesterol to the cell surface
      whether de novo synthesized or delivered as low density lipoprotein, and overall
      cellular content of cholesterol, although biosynthesis of lipids from acetate was
      somewhat increased. Probucol did not affect the mRNA level of ABCA1, and ABCA1
      was recovered along with marker proteins for plasma membrane regardless of the
      presence of probucol. However, the protein level of ABCA1 increased, and the rate
      of its decay in the presence of cycloheximide was slower in the probucol-treated
      cells. ABCA1 in the probucol-treated cells was resistant to digestion by calpain
      but not by trypsin. We concluded that probucol inactivates ABCA1 in the plasma
      membrane with respect to its function in mediating binding of and lipid release
      by apolipoprotein and with respect to proteolytic degradation by calpain.

PMID- 15140890
TI  - A mutation inactivating the mitochondrial inner membrane folate transporter
      creates a glycine requirement for survival of chinese hamster cells.
AB  - A mutant Chinese hamster ovary cell line, glyB, that required exogenous glycine
      for survival and growth was reported previously (Kao, F., Chasin, L., and Puck,
      T. T. (1969) Proc. Natl. Acad. Sci. U. S. A. 64, 1284-1291). We now report that
      the defect in glyB cells causative of this phenotype is a point mutation in an
      inner mitochondrial membrane protein required for transport of folates into
      mitochondria. The CHO mitochondrial folate transporter (mft) was sequenced and
      compared with that from glyB cells. The hamster sequence was nearly identical to
      that of the recently reported human mitochondrial folate transporter. The
      corresponding cDNA from glyB cells contained a single nucleotide change that
      introduced a glutamate in place of the glycine in wild-type hamster MFT at codon
      192 in a predicted transmembrane domain. Transfection of the wild-type hamster
      cDNA into glyB cells allowed cell survival in the absence of glycine and the
      accumulation of folates in mitochondria, whereas transfection of the Glu-192 cDNA
      did not. Genomic sequence analysis and fluorescence in situ hybridization
      demonstrated a single mutated allele of the mft gene in glyB cells, whereas there
      were two alleles in CHO cells. We conclude that we have defined the cause of the
      glyB auxotrophy and that the glyB mft mutation identified a region of this
      mitochondrial folate carrier vital to its transport function.

PMID- 15140891
TI  - Definition of a consensus DNA-binding site for PecS, a global regulator of
      virulence gene expression in Erwinia chrysanthemi and identification of new
      members of the PecS regulon.
AB  - In Erwinia chrysanthemi, production of pectic enzymes is modulated by a complex
      network involving several regulators. One of them, PecS, which belongs to the
      MarR family, also controls the synthesis of various other virulence factors, such
      as cellulases and indigoidine. Here, the PecS consensus-binding site is defined
      by combining a systematic evolution of ligands by an exponential enrichment
      approach and mutational analyses. The consensus consists of a 23-base pair
      palindromic-like sequence (C(-11)G(-10)A(-9)N(-8)W(-7)T(-6)C(-5)G(-4)T(-3)A(
      2))T(-1)A(0)T(1)(T(2)A(3)C(4)G(5)A(6)N(7)N(8)N(9)C(10)G(11)). Mutational
      experiments revealed that (i) the palindromic organization is required for the
      binding of PecS, (ii) the very conserved part of the consensus (-6 to 6) allows
      for a specific interaction with PecS, but the presence of the relatively
      degenerated bases located apart significantly increases PecS affinity, (iii) the
      four bases G, A, T, and C are required for efficient binding of PecS, and (iv)
      the presence of several binding sites on the same promoter increases the affinity
      of PecS. This consensus is detected in the regions involved in PecS binding on
      the previously characterized target genes. This variable consensus is in
      agreement with the observation that the members of the MarR family are able to
      bind various DNA targets as dimers by means of a winged helix DNA-binding motif.
      Binding of PecS on a promoter region containing the defined consensus results in
      a repression of gene transcription in vitro. Preliminary scanning of the E.
      chrysanthemi genome sequence with the consensus revealed the presence of strong
      PecS-binding sites in the intergenic region between fliE and fliFGHIJKLMNOPQR
      which encode proteins involved in the biogenesis of flagellum. Accordingly, PecS
      directly represses fliE expression. Thus, PecS seems to control the synthesis of
      virulence factors required for the key steps of plant infection.

PMID- 15140892
TI  - Targeting and translocation of two lipoproteins in Escherichia coli via the
      SRP/Sec/YidC pathway.
AB  - In Escherichia coli, two main protein targeting pathways to the inner membrane
      exist: the SecB pathway for the essentially posttranslational targeting of
      secretory proteins and the SRP pathway for cotranslational targeting of inner
      membrane proteins (IMPs). At the inner membrane both pathways converge at the Sec
      translocase, which is capable of both linear transport into the periplasm and
      lateral transport into the lipid bilayer. The Sec-associated YidC appears to
      assist the lateral transport of IMPs from the Sec translocase into the lipid
      bilayer. It should be noted that targeting and translocation of only a handful of
      secretory proteins and IMPs have been studied. These model proteins do not
      include lipoproteins. Here, we have studied the targeting and translocation of
      two secretory lipoproteins, the murein lipoprotein and the bacteriocin release
      protein, using a combined in vivo and in vitro approach. The data indicate that
      both murein lipoprotein and bacteriocin release protein require the SRP pathway
      for efficient targeting to the Sec translocase. Furthermore, we show that YidC
      plays an important role in the targeting/translocation of both lipoproteins.

PMID- 15140893
TI  - Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate
      receptor activity through WD40 motif-mediated dimerization.
AB  - Efficient signaling requires accurate spatial and temporal compartmentalization
      of proteins. RACK1 is a scaffolding protein that fulfils this role through
      interaction of binding partners with one of its seven WD40 domains. We recently
      identified the kinase Fyn and the NR2B subunit of the N-methyl-D-Aspartate
      receptor (NMDAR) as binding partners of RACK1. Scaffolding of Fyn near its
      substrate NR2B by RACK1 inhibits Fyn phosphorylation of NR2B and thereby
      negatively regulates channel function. We found that Fyn and NR2B share the same
      binding site on RACK1; however, their binding to RACK1 is not mutually exclusive
      (Yaka, R., Thornton, C., Vagts, A. J., Phamluong, K., Bonci, A., and Ron, D.
      (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5710-5715). We therefore tested the
      hypothesis that RACK1 forms a homodimer that allows the simultaneous binding of
      Fyn and NR2B. We found that RACK1 binds to itself both in vitro and in the brain.
      Deletion analyses identified a RACK1-RACK1 dimer-binding site within the 4th WD40
      repeat, and application of the 4th WD40 repeat or a peptide derivative to
      hippocampal slices inhibited NMDAR activity. We further found that in hippocampal
      slices, both RACK1 and NR2B associated with another WD40 protein, the beta
      subunit of G protein (Gbeta), previously shown to heterodimerize with RACK1 in
      vitro (Dell, E. J., Connor, J., Chen, S., Stebbins, E. G., Skiba, N. P., Mochly
      Rosen, D., and Hamm, H. E. (2002) J. Biol. Chem. 277, 49888-49895). However,
      activation of the pituitary adenylate cyclase polypeptide (1-38) G protein
      coupled receptor, previously found to induce the dissociation of RACK1 from the
      NMDAR complex (Yaka, R., He, D. Y., Phamluong, K., and Ron, D. (2003) J. Biol.
      Chem. 278, 9630-9638), attenuated the association of Gbeta with RACK1 and NR2B.
      Based on these results, we propose that WD40-mediated homo- and
      heterodimerization of RACK1 mediate the formation of a transient signaling
      complex that includes the NMDAR, a G protein and Fyn.

PMID- 15140894
TI  - Involvement of LMO7 in the association of two cell-cell adhesion molecules,
      nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells.
AB  - Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules
      that are involved in formation of cadherin-based adherens junctions (AJs). The
      nectin-based cell-cell adhesion induces activation of Cdc42 and Rac small G
      proteins, which eventually enhances the formation of AJs through reorganization
      of the actin cytoskeleton. Although evidence has accumulated that nectins recruit
      cadherins to the nectin-based cell-cell adhesion sites through their cytoplasm
      associated proteins, afadin and catenins, it is not fully understood how nectins
      are physically associated with cadherins. Here we identified a rat counterpart of
      the human LIM domain only 7 (LMO7) as an afadin- and alpha-actinin-binding
      protein. Rat LMO7 has two splice variants, LMO7a and LMO7b, consisting of 1,729
      and 1,395 amino acids, respectively. LMO7 has calponin homology, PDZ, and LIM
      domains. Western blotting revealed that LMO7 was expressed ubiquitously in
      various rat tissues. Immunofluorescence and immunoelectron microscopy revealed
      that LMO7 localized at cell-cell AJs, where afadin localized, in epithelial cells
      of rat gallbladder. In addition, LMO7 localized at the cytoplasmic faces of
      apical membranes in the same epithelial cells. We furthermore revealed that LMO7
      bound alpha-actinin, an actin filament-bundling protein, which bound to alpha
      catenin. Immunoprecipitation analysis revealed that LMO7 was associated with both
      the nectin-afadin and E-cadherin-catenin systems. LMO7 was assembled at the cell
      cell adhesion sites after both the nectin-afadin and E-cadherin-catenin systems
      had been assembled. These results indicate that LMO7 is an afadin- and alpha
      actinin-binding protein that connects the nectin-afadin and E-cadherin-catenin
      systems through alpha-actinin.

PMID- 15140895
TI  - Antifreeze protein-induced morphological modification mechanisms linked to ice
      binding surface.
AB  - The mechanisms by which the antifreeze protein (AFP) modifies the ice morphology
      are identified precisely as surface poisoning by the ice binding surface (IBS) of
      insect AFPs and as bridge-induced surface reconstruction by the IBS of fish AFPs
      and antifreeze glycoproteins. The primary surfaces of hexagonal ice have
      predetermined face indices. The "two-dimensional" insect type IBS has regularly
      spaced binding intervals in two directions. It causes surface poisoning by
      matching and reinforcing simultaneously intersecting strong bonding directions on
      the primary ice surfaces. The secondary ice surfaces have variable face indices.
      The "one-dimensional" and "irregular" IBS variants of fish AFPs and antifreeze
      glycoproteins are either linearly extended with regular ice binding intervals or
      have ice binding sites lacking spacing regularity. These variants can bridge
      transversely lattice periods or shorter oxygen-oxygen distances between parallel
      adjacent strong bonding directions that do not intersect. Thus, one-dimensional
      and irregular IBS variants induce supplementary bridges cross-wise on selected
      secondary surfaces by mimicking strong bonding directions that are not present in
      the ice structure. These proteins cause surfaces with variable face indices,
      which in the absence of the AFPs would not grow flat, to appear in the
      morphology. Whereas for the primary ice surfaces it is only the morphological
      importance that is determined by the experimental conditions, for the secondary
      ice surfaces it is the face indices themselves that become adjusted in the
      process of maximizing the AFP-substrate interaction through attainment of the
      best structural match. The growth morphology of the AFP-ice system is derived
      from various factors, including the face indices, surface molecular compositions,
      relative growth rates, and the mechanisms responsible for that morphology. The
      theoretical formulation agrees with experiments over a wide range and resolves
      these, to date, unexplained phenomena.

PMID- 15140896
TI  - Furin inhibition by compounds of copper and zinc.
AB  - Furin, a human subtilisin-related proprotein convertase (SPC), is emerging as an
      important pharmaceutical target because it processes vital proteins of many
      aggressive pathogens. Furin inhibitors reported as yet are peptide derivatives
      and proteins, with the exception of andrographolides, which are natural
      compounds. Here we report that the small and highly stable compounds
      M(chelate)Cl(2) (M is copper or zinc) inhibit furin and Kex2, with Cu(TTP)Cl(2)
      and Zn(TTP)Cl(2) as the most efficient inhibitors. (TTP is 4'-[p-tolyl]-2,2
      ':6',2"-terpyridine.) Inhibition is irreversible, competitive with substrate, and
      affected by substituents on the chelate. The free chelates are not inhibitors.
      Solvated Zn(2+) is less potent than its complexes. This is true also for copper
      and Kex2. However, solvated Cu(2+) (k(on) of 25,000 +/- 2,500 s(-1)) is more
      potent than Cu(TTP)Cl(2) (k(on) = 140 +/- 13 s(-1) and allows recovery of furin
      activity prior to a second inhibition phase. A mechanism that involves
      coordination to the catalytic histidine is proposed for all inhibitors. Target
      specificity is indicated by the fact that these metal chelate inhibitors are much
      less potent toward Kex2, the yeast homologue of furin. For example, k(on) with
      Zn(TTP)Cl(2) is 120 +/- 20 s(-1) for furin, but only 1.2 +/- 0.1 s(-1) for Kex2.

PMID- 15140897
TI  - Reduced pain hypersensitivity and inflammation in mice lacking microsomal
      prostaglandin e synthase-1.
AB  - We examined the in vivo role of membrane-bound prostaglandin E synthase (mPGES)
      1, a terminal enzyme in the PGE2-biosynthetic pathway, using mPGES-1 knockout
      (KO) mice. Comparison of PGES activity in the membrane fraction of tissues from
      mPGES-1 KO and wild-type (WT) mice indicated that mPGES-1 accounted for the
      majority of lipopolysaccharide (LPS)-inducible PGES in WT mice. LPS-stimulated
      production of PGE2, but not other PGs, was impaired markedly in mPGES-1-null
      macrophages, although a low level of cyclooxygenase-2-dependent PGE2 production
      still remained. Pain nociception, as assessed by the acetic acid writhing
      response, was reduced significantly in KO mice relative to WT mice. This
      phenotype was particularly evident when these mice were primed with LPS, where
      the stretching behavior and the peritoneal PGE2 level of KO mice were far less
      than those of WT mice. Formation of inflammatory granulation tissue and attendant
      angiogenesis in the dorsum induced by subcutaneous implantation of a cotton
      thread were reduced significantly in KO mice compared with WT mice. Moreover,
      collagen antibody-induced arthritis, a model for human rheumatoid arthritis, was
      milder in KO mice than in WT mice. Collectively, our present results provide
      unequivocal evidence that mPGES-1 contributes to the formation of PGE2 involved
      in pain hypersensitivity and inflammation.

PMID- 15140898
TI  - Vgl-4, a novel member of the vestigial-like family of transcription cofactors,
      regulates alpha1-adrenergic activation of gene expression in cardiac myocytes.
AB  - Cardiac and skeletal muscle genes are regulated by the transcriptional enhancer
      factor (TEF-1) family of transcription factors. In skeletal muscle, TEF-1 factors
      interact with a skeletal muscle-specific cofactor called Vestigial-like 2 (Vgl-2)
      that is related to the Drosophila protein Vestigial. Here, we characterize Vgl-4,
      the only member of the Vestigial-like family expressed in the heart. Unlike other
      members of the Vgl family that have a single TEF-1 interaction domain called the
      tondu (TDU) motif, Vgl-4 has two TDU motifs in its carboxyl-terminal domain. Like
      other Vgl factors, Vgl-4 physically interacts with TEF-1 in an
      immunoprecipitation assay. Vgl-4 functionally interacts with TEF-1 and also with
      myocyte enhancer factor 2 in a mammalian two-hybrid assay. Overexpression of Vgl
      4 in cardiac myocytes interfered with the basal expression and alpha1-adrenergic
      receptor-dependent activation of a TEF-1-dependent skeletal alpha-actin promoter.
      In cardiac myocytes cultured in serum and in serum-free medium, a myc-tagged Vgl
      4 protein was located in the nucleus and cytoplasm but was exported from the
      nucleus when cells were treated with alpha1-adrenergic receptor agonist. A
      chimeric nuclear-retained Vgl-4 protein inhibited alpha1-adrenergic receptor
      dependent activation. In contrast, deletion of the TDU motifs of Vgl-4 prevented
      Vgl-4 nuclear localization, relieved Vgl-4 interference of basal activity, and
      enhanced alpha1-adrenergic up-regulation of the skeletal alpha-actin promoter.
      Nuclear export of Vgl-4 is dependent on the nuclear exportin CRM-1. These results
      suggest that Vgl-4 modulates the activity of TEF-1 factors and counteracts alpha1
      adrenergic activation of gene expression in cardiac myocytes.

PMID- 15140901
TI  - Quantitative investigation of calcium signals for locomotor pattern generation in
      the lamprey spinal cord.
AB  - Locomotor pattern generation requires the network coordination of spinal ventral
      horn neurons acting in concert with the oscillatory properties of individual
      neurons. In the spinal cord, N-methyl-d-aspartate (NMDA) activates neuronal
      oscillators that are believed to rely on Ca(2+) entry to the cytosol through
      voltage-operated Ca(2+) channels and synaptically activated NMDA receptors.
      Ca(2+) signaling in lamprey ventral horn neurons thus plays a determinant role in
      the regulation of the intrinsic membrane properties and network synaptic
      interaction generating spinal locomotor neural pattern activity. We have
      characterized aspects of this signaling quantitatively for the first time.
      Resting Ca(2+) concentrations were between 87 and 120 nM. Ca(2+) concentration
      measured during fictive locomotion increased from soma to distal dendrites [from
      208 +/- 27 (SE) nM in the soma to 335 +/- 41 nM in the proximal dendrites to 457
      +/- 68 nM in the distal dendrites]. We sought to determine the temporal and
      spatial properties of Ca(2+) oscillations, imaged with Ca(2+)-sensitive dyes and
      correlated with fluctuations in membrane potential, during lamprey fictive
      locomotion. The Ca(2+) signals recorded in the dendrites showed a great deal of
      spatial heterogeneity. Rapid changes in Ca(2+)-induced fluorescence coincided
      with action potentials, which initiated significant Ca(2+) transients distributed
      throughout the neurons. Ca(2+) entry to the cytosol coincided with the
      depolarizing phase of the locomotor rhythm. During fictive locomotion, larger
      Ca(2+) oscillations were recorded in dendrites compared with somata in
      motoneurons and premotor interneurons. Ca(2+) fluctuations were barely detected
      with dyes of lower affinity providing alternative empirical evidence that Ca(2+)
      responses are limited to hundreds of nanomolars during fictive locomotion.

PMID- 15140899
TI  - Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs
      hippocampal axonal targeting and promotes fear behavior.
AB  - Polysialic acid (PSA) is a post-translational protein modification that is widely
      expressed among neural cell types during development. Found predominantly on the
      neural cell adhesion molecule (NCAM), PSA becomes restricted to regions of
      neurogenesis and neuroplasticity in the adult. In the mammalian genome, two
      polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to
      be responsible for the production of PSA in vivo. Approaches to discover PSA
      function have involved the application of endoneuraminidase-N to remove PSA and
      genetic manipulations in the mouse to deplete either NCAM or ST8Sia-IV. Here we
      report the production and characterization of mice deficient in the ST8Sia-II
      polysialyltransferase. We observed alterations in brain PSA expression unlike
      those observed in mice lacking ST8Sia-IV. This included a PSA deficit in regions
      of neurogenesis but without changes in the frequency of mitotic neural progenitor
      cells. In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not
      impair hippocampal synaptic plasticity but instead resulted in the misguidance of
      infrapyramidal mossy fibers and the formation of ectopic synapses in the
      hippocampus. Consistent with studies of animal models bearing these morphological
      changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced
      behavioral responses to Pavlovian fear conditioning. PSA produced by the ST8Sia
      II polysialyltransferase modifies memory and behavior processes that are distinct
      from the neural roles reported for ST8Sia-IV. This genetic partitioning of PSA
      formation engenders discrete neurological processes and reveals that this post
      translational modification forms the predominant basis for the multiple functions
      attributed to the NCAM glycoprotein.

PMID- 15140902
TI  - Unilateral labyrinthectomy modifies the membrane properties of contralesional
      vestibular neurons.
AB  - Vestibular compensation after a unilateral labyrinthectomy leads to nearly
      complete disappearance of the static symptoms triggered by the lesion. However,
      the dynamic vestibular reflexes associated with head movements remain impaired.
      Because the contralesional labyrinth plays a prominent role in the generation of
      these dynamic responses, intracellular recordings of contralesional medial
      vestibular nucleus neurons (MVNn) were done after 1 mo of compensation. Their
      firing properties and cell type were characterized at rest, and their response
      dynamics investigated using step, ramp, and sinusoidal current stimulations. The
      sensitivity of the contralesional MVNn firing rates to applied current was
      increased, which, along with increased phase leads, suggests that significant
      changes in active conductances occurred. We found an increased proportion of the
      phasic type B neurons relative to the tonic type A neurons in the contralesional
      MVN. In addition, the remaining contralesional type A MVNn response dynamics
      tended to approach those of type B MVNn. Thus the contralesional MVNn in general
      showed more phasic response dynamics than those of control MVNn. Altogether, the
      firing properties of MVNn are differentially modified on the ipsilesional and
      contralesional sides of the brain stem 1 mo after unilateral labyrinthectomy.
      Ipsilesional MVNn acquire more "type A-like" tonic membrane properties, which
      would contribute to the stabilization of the spontaneous activity that recovers
      in the deafferented neurons during vestibular compensation. The bilateral
      increase in the sensitivity of MVNn and the acquisition of more "B-like" phasic
      membrane properties by contralesional MVNn should promote the restoration of the
      vestibular reflexes generated by the remaining, contralesional labyrinth.

PMID- 15140903
TI  - Serotonergic modulation in aplysia. I. Distributed serotonergic network
      persistently activated by sensitizing stimuli.
AB  - A common feature of arousing stimuli used as reinforcement in animal models of
      learning is that they promote memory formation through widespread effects in the
      CNS. In the marine mollusk Aplysia, sensitization is typically induced by tail
      shock, an aversive reinforcer that triggers a state of defensive arousal
      characterized by escape locomotion and increased heart rate. Serotonin (5-HT)
      contributes importantly to sensitization of defensive reflexes as well as to the
      regulation of locomotion and heart rate. Although specific serotonergic neurons
      increase their firing after tail-shock, it remains unclear whether this effect is
      restricted to these neurons or whether tail-shock recruits a more global
      serotonergic system. In this study, we recorded from serotonergic neurons
      throughout the CNS, which were prelabeled with 5,7-dihydroxytryptamine, during an
      in vitro analog of sensitization training, tail-nerve shock. We found that most
      of the serotonergic neurons that we recorded from (80%) increased their firing
      rate for several minutes after nerve shock. Most serotonergic neurons in the
      pedal and abdominal ganglion were also excited by 5-HT and by intracellular
      activation of the two serotonergic neurons CB1/CC3. This interconnectivity
      between serotonergic neurons might contribute to spread excitation within a large
      proportion of the serotonergic system during sensitization training. It is also
      possible that serotonergic neurons could be activated by 5-HT present in the
      hemolymph via a neuro-humoral positive feedback mechanism. Overall, these data
      indicate that sensitization training activates a large proportion of Aplysia
      serotonergic neurons and that this form of learning occurs in a context of
      increased serotonergic tone.

PMID- 15140904
TI  - Serotonergic modulation in aplysia. II. Cellular and behavioral consequences of
      increased serotonergic tone.
AB  - Serotonin (5-HT) plays an important role in sensitization of defensive reflexes
      in Aplysia and is also involved in several aspects of arousal, such as the
      control of locomotion and of cardiovascular tone. In the preceding paper, we
      showed that tail-nerve shock, a noxious stimulus that readily induces
      sensitization, increases the firing rate of a large number of serotonergic
      neurons throughout the CNS. However, the functional consequences of such an
      increase in serotonergic tone are still poorly understood. In this study, we
      examined this question by using the 5-HT precursor 5-hydroxytryptophan (5-HTP) to
      specifically increase 5-HT release in the CNS. Increased tonic 5-HT release after
      5-HTP treatment was manifested by facilitation of sensorimotor (SN-MN) synapses,
      increased firing rate of serotonergic neurons in the pedal and abdominal ganglia,
      and enhanced 5-HT release evoked by tail-nerve shock. When 5-HTP was administered
      to freely moving animals, it produced a strong arousal response characterized by
      increased locomotion and heart rate, which was reminiscent of the defensive
      arousal reaction triggered by noxious stimulation such as tail-shock. In
      contrast, 5-HTP actually inhibited the tail-induced siphon-withdrawal reflex. It
      is possible that 5-HT-induced facilitation of SN-MN synapses was counteracted by
      inhibition of polysynaptic reflex pathways between SNs and MNs, resulting in
      transient behavioral inhibition of the reflex, which could favor escape
      locomotion and/or respiration shortly after an aversive stimulus. We conclude
      that a major function associated with the activation of the Aplysia serotonergic
      system evoked by noxious stimuli is the triggering of a defensive arousal
      response. It is known that tail-shock-induced serotonergic activation contributes
      to memory encoding at least in part by facilitating SN-MN synapses. However, this
      effect in isolation might not be sufficient for the behavioral expression of
      sensitization.

PMID- 15140905
TI  - Major role for tonic GABAA conductances in anesthetic suppression of intrinsic
      neuronal excitability.
AB  - Anesthetics appear to produce neurodepression by altering synaptic transmission
      and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has
      proposed effects on many targets, ranging from sodium channels to GABA(A)
      inhibition. We examined effects of propofol on the intrinsic excitability of
      hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain
      slices. Propofol strongly depressed action potential production induced by DC
      injection, synaptic stimulation, or high-potassium solutions. Propofol-induced
      depression of intrinsic excitability was completely reversed by bicuculline and
      picrotoxin but was strychnine-insensitive, implicating GABA(A) but not glycine
      receptors. Propofol strongly enhanced inhibitory postsynaptic currents (IPSCs)
      and induced a tonic GABA(A)-mediated current. We pharmacologically differentiated
      tonic and phasic (synaptic) GABA(A)-mediated inhibition using the GABA(A)
      receptor antagonist SR95531 (gabazine). Gabazine (20 microM) completely blocked
      both evoked and spontaneous IPSCs but failed to block the propofol-induced
      depression of intrinsic excitability, implicating tonic, but not phasic, GABA(A)
      inhibition. Glutamatergic synaptic responses were not altered by propofol (< or
      =30 microM). Similar results were found in both interneurons and pyramidal cells
      and with the chemically unrelated anesthetic thiopental. These results suggest
      that suppression of CA1 neuron intrinsic excitability, by these anesthetics, is
      largely due to activation of tonic GABA(A) conductances; although other sites of
      action may play important roles in affecting synaptic transmission, which also
      can produce strong neurodepression. We propose that for some anesthetics,
      suppression of intrinsic excitability, mediated by tonic GABA(A) conductances,
      operates in conjunction with effects on synaptic transmission, mediated by other
      mechanisms, to depress hippocampal function during anesthesia.

PMID- 15140906
TI  - Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds.
AB  - Sour (acid) taste is postulated to result from intracellular acidification that
      modulates one or more acid-sensitive ion channels in taste receptor cells. The
      identity of such channel(s) remains uncertain. Potassium channels, by regulating
      the excitability of taste cells, are candidates for acid transducers. Several 2
      pore domain potassium leak conductance channels (K(2)P family) are sensitive to
      intracellular acidification. We examined their expression in mouse vallate and
      foliate taste buds using RT-PCR, and detected TWIK-1 and -2, TREK-1 and -2, and
      TASK-1. Of these, TWIK-1 and TASK-1 were preferentially expressed in taste cells
      relative to surrounding nonsensory epithelium. The related TRESK channel was not
      detected, whereas the acid-insensitive TASK-2 was. Using confocal imaging with pH
      , Ca(2+)-, and voltage-sensitive dyes, we tested pharmacological agents that are
      diagnostic for these channels. Riluzole (500 microM), selective for TREK-1 and -2
      channels, enhanced acid taste responses. In contrast, halothane (< or =
      approximately 17 mM), which acts on TREK-1 and TASK-1 channels, blocked acid
      taste responses. Agents diagnostic for other 2-pore domain and voltage-gated
      potassium channels (anandamide, 10 microM; Gd(3+), 1 mM; arachidonic acid, 100
      microM; quinidine, 200 microM; quinine, 100 mM; 4-AP, 10 mM; and TEA, 1 mM) did
      not affect acid responses. The expression of 2-pore domain channels and our
      pharmacological characterization suggest that a matrix of ion channels, including
      one or more acid-sensitive 2-pore domain K channels, could play a role in sour
      taste transduction. However, our results do not unambiguously identify any one
      channel as the acid taste transducer.

PMID- 15140907
TI  - Relative distribution of Ca2+ channels at the crayfish inhibitory neuromuscular
      junction.
AB  - We investigated the Ca(2+) channel-synaptic vesicle topography at the inhibitor
      of the crayfish (Procambarus Clarkii) neuromuscular junction (NMJ) by analyzing
      the effect of different modes of Ca(2+) channel block on transmitter release.
      Initial identification of Ca(2+) channels revealed the presence of two classes, P
      and non-P-type with P-type channels governing approximately 70% of the total
      Ca(2+) influx. The remaining Ca(2+) influx was completely blocked by Cd(2+) but
      not by saturating concentrations of omega-conotoxins MVIIC and GVIA, or
      nifedipine and SNX-482. To examine the relative spatial distribution of Ca(2+)
      channels with respect to synaptic vesicles, we compared changes in inhibitory
      postsynaptic current amplitude and synaptic delay resulting from different
      spatial profiles of [Ca(2+)](i) around release sites. Specifically, addition of
      either [Mg(2+)](o), which decreases single-channel current, or omega-Aga IVA,
      which completely blocks P-type channels, prolonged synaptic delay by a similar
      amount when Ca(2+) influx block was <40%. Because non-P-type channels are able to
      compensate for blocked P-type channels, it suggests that these channels overlap
      considerably in their distribution. However, when Ca(2+) influx was blocked by
      approximately 50%, omega-Aga IVA increased delay significantly more than Mg(2+),
      suggesting that P-type channels are located closer than non-P-type channels to
      synaptic vesicles. This distribution of Ca(2+) channels was further supported by
      the observations that non-P-type channels are unable to trigger release in
      physiological saline and EGTA preferentially prolongs synaptic delay dominated by
      non-P-type channels when transmitter release is evoked with broad action
      potentials. We therefore conclude that although non-P-type channels do not
      directly trigger release under physiological conditions, their distribution
      partially overlaps with P-type channels.

PMID- 15140908
TI  - Somatosensory corticothalamic projections: distinguishing drivers from
      modulators.
AB  - We used a juvenile mouse thalamocortical slice preparation with whole cell
      recording to investigate synaptic properties of corticothalamic inputs from
      somatosensory cortex to the ventral posterior medial and posterior medial nuclei
      (98 cells). We compared these data to those obtained from activating retinal and
      cortical inputs to the lateral geniculate nucleus (8 cells), the former
      representing a prototypical driver input and the latter, a typical modulator.
      Retinogeniculate activation evoked large, all-or-none excitatory postsynaptic
      potentials (EPSPs) that showed paired-pulse depression antagonized by N-methyl-d
      aspartate (NMDA) and AMPA receptor blockers but with no sign of a metabotropic
      glutamate receptor (mGluR) component. Corticogeniculate activation evoked small,
      graded EPSPs showing paired-pulse facilitation, and the EPSPs showed both NMDA
      and AMPA receptor component plus an mGluR1 component. In the somatosensory
      thalamic relays, cortical stimulation elicited glutamatergic EPSPs in all
      thalamic cells, and these EPSPs fell into two groups. One, elicited from cortical
      layer 6 to cells of both nuclei, involved small, graded EPSPs with paired-pulse
      facilitation, and most also showed an mGluR1 component. The other, elicited from
      layer 5 to cells only of the posterior medial nucleus, involved large, all-or
      none EPSPs with paired-pulse depression, and none showed an mGluR component. By
      analogy with results from the lateral geniculate nucleus, we conclude that the
      input from layer 6 to both nuclei acts as a modulator but that the layer 5 input
      to the posterior medial nucleus serves as a driver. Our data extend a common
      organizing principle from first-order nuclei to higher-order thalamic relays and
      further implicate the latter in corticocortical communication.

PMID- 15140909
TI  - Fast inhibition alters first spike timing in auditory brainstem neurons.
AB  - Within the first processing site of the central auditory pathway, inhibitory
      neurons (D stellate cells) broadly tuned to tonal frequency project on narrowly
      tuned, excitatory output neurons (T stellate cells). The latter is thought to
      provide a topographic representation of sound spectrum, whereas the former is
      thought to provide lateral inhibition that improves spectral contrast,
      particularly in noise. In response to pure tones, the overall discharge rate in T
      stellate cells is unlikely to be suppressed dramatically by D stellate cells
      because they respond primarily to stimulus onset and provide fast, short-duration
      inhibition. In vivo intracellular recordings from the ventral cochlear nucleus
      (VCN) showed that, when tones were presented above or below the characteristic
      frequency (CF) of a T stellate neuron, they were inhibited during depolarization.
      This resulted in a delay in the initial action potential produced by T stellate
      cells. This ability of fast inhibition to alter the first spike timing of a T
      stellate neuron was confirmed by electrically activating the D stellate cell
      pathway that arises in the contralateral cochlear nucleus. Delay was also induced
      when two tones were presented: one at CF and one outside the frequency response
      area of the T stellate neuron. These findings suggest that the traditional view
      of lateral inhibition within the VCN should incorporate delay as one of its
      principle outcomes.

PMID- 15140910
TI  - Controlling human upright posture: velocity information is more accurate than
      position or acceleration.
AB  - The problem of how the nervous system fuses sensory information from multiple
      modalities for upright stance control remains largely unsolved. It is well
      established that the visual, vestibular, and somatosensory modalities provide
      position and rate (e.g., velocity, acceleration) information for estimation of
      body dynamics. However, it is unknown whether any particular property dominates
      when multisensory information is fused. Our recent stochastic analysis of
      postural sway during quiet stance suggested that sensory input provides more
      accurate information about the body's velocity than its position or acceleration.
      Here we tested this prediction by degrading major sources of velocity information
      through removal/attenuation of sensory information from vision and
      proprioception. Experimental measures of postural sway were compared with model
      predictions to determine whether sway behavior was indicative of a deficit in
      velocity information rather than position or acceleration information. Subjects
      stood with eyes closed on a support surface that was 1) fixed, 2) foam, or 3)
      sway-referenced. Six measures characterizing the stochastic structure of postural
      sway behaved in a manner consistent with model predictions of degraded velocity
      information. Results were inconsistent with the effect of degrading only position
      or acceleration information. These findings support the hypothesis that velocity
      information is the most accurate form of sensory information used to stabilize
      posture during quiet stance. Our results are consistent with the assumption that
      changes in sway behavior resulting from commonly used experimental manipulations
      (e.g., foam, sway-referencing, eyes closed) are primarily attributed to loss of
      accurate velocity information.

PMID- 15140911
TI  - Neuronal activity throughout the primate mediodorsal nucleus of the thalamus
      during oculomotor delayed-responses. I. Cue-, delay-, and response-period
      activity.
AB  - The thalamic mediodorsal nucleus (MD) has strong reciprocal connections with the
      dorsolateral prefrontal cortex (DLPFC), suggesting that the MD, like the DLPFC,
      participates in higher cognitive functions. To examine MD's participation in
      cognitive functions, we analyzed the characteristics of task-related activities
      sampled homogeneously from the MD while two monkeys performed a spatial working
      memory task using oculomotor responses. Of 141 task-related MD neurons, 26, 53,
      and 84% exhibited cue-, delay-, and response-period activity, respectively. Most
      of cue- and response-period activities showed phasic excitation, and most of
      delay-period activity showed tonic sustained activation. Among neurons with
      response-period activity, 74% exhibited presaccadic activity. Most cue-period,
      delay-period, and presaccadic activities were directional, whereas most
      postsaccadic activity was omni-directional. A significant contralateral bias in
      the best directions was present in cue-period and presaccadic activity. However,
      such bias was not present in delay-period activity, although most neurons had a
      best direction toward the contralateral visual field. We compared these
      characteristics with those observed in DLPFC neurons. Response-period activity
      was more frequently observed in the MD (84%) than in the DLPFC (56%). The
      directional selectivity and bias of task-related activities and the ratios of pre
      and postsaccadic activities were different between MD and DLPFC. These results
      indicate that the MD participates in higher cognitive functions such as spatial
      working memory. However, the manner in which these two structures participate in
      these processes differs, in that the MD participates more in motor control
      aspects compared with the DLPFC.

PMID- 15140912
TI  - Neuronal activity throughout the primate mediodorsal nucleus of the thalamus
      during oculomotor delayed-responses. II. Activity encoding visual versus motor
      signal.
AB  - We collected single-neuron activity from the mediodorsal (MD) nucleus of the
      thalamus, examined the information that was represented by task-related activity
      during performance of a spatial working memory task, and compared the present
      results with those obtained in the dorsolateral prefrontal cortex (DLPFC). We
      used two oculomotor delayed-response (ODR) tasks. In the ordinary ODR task,
      monkeys were required to make a memory-guided saccade to the location where a
      visual cue had been presented 3 s previously, whereas in the rotatory ODR task,
      they were required to make a memory-guided saccade 90 degrees clockwise from the
      cue direction. By comparing the best directions of the same task-related activity
      between the two tasks, we could determine whether this activity represented the
      cue location or the saccade direction. All cue-period activity represented the
      cue location. In contrast, 56% of delay-period activity represented the cue
      location and 41% represented the saccade direction. Almost all response-period
      activity represented the saccade direction. These results indicate that task
      related MD activity represents either visual or motor information, suggesting
      that the MD participates in sensory-to-motor information processing. However, a
      greater proportion of delay- and response-period activities represented the
      saccade direction in the MD than in the DLPFC, indicating that more MD neurons
      participate in prospective information processing than DLPFC neurons. These
      results suggest that although functional interactions between the MD and DLPFC
      are crucial to cognitive functions such as working memory, there is a difference
      in how the MD and DLPFC participate in these functions.

PMID- 15140913
TI  - 3-[2-cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate
      (BAY 59-3074): a novel cannabinoid Cb1/Cb2 receptor partial agonist with
      antihyperalgesic and antiallodynic effects.
AB  - 3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate
      (BAY 59-3074) is a novel, selective cannabinoid CB(1)/CB(2) receptor ligand (K(i)
      = 55.4, 48.3, and 45.5 nM at rat and human cannabinoid CB(1) and human CB(2)
      receptors, respectively), with partial agonist properties at these receptors in
      guanosine 5-[gamma(35)S]-thiophosphate triethyl-ammonium salt ([(35)S]GTPgammaS)
      binding assays. In rats, generalization of BAY 59-3074 to the cue induced by the
      cannabinoid CB(1) receptor agonist (-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl
      4,4,4-trifluoro-1-butanesulfonate (BAY 38-7271) in a drug discrimination
      procedure, as well as its hypothermic and analgesic effects in a hot plate assay,
      were blocked by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride (SR 141716A). BAY 59-3074 (0.3-3 mg/kg, p.o.) induced
      antihyperalgesic and antiallodynic effects against thermal or mechanical stimuli
      in rat models of chronic neuropathic (chronic constriction injury, spared nerve
      injury, tibial nerve injury, and spinal nerve ligation models) and inflammatory
      pain (carrageenan and complete Freund's adjuvant models). Antiallodynic efficacy
      of BAY 59-3074 (1 mg/kg, p.o.) in the spared nerve injury model was maintained
      after 2 weeks of daily administration. However, tolerance developed rapidly
      (within 5 days) for cannabinoid-related side effects, which occur at doses above
      1 mg/kg (e.g., hypothermia). Uptitration from 1 to 32 mg/kg p.o. (doubling of
      daily dose every 4th day) prevented the occurrence of such side effects, whereas
      antihyperalgesic and antiallodynic efficacy was maintained/increased. No
      withdrawal symptoms were seen after abrupt withdrawal following 14 daily
      applications of 1 to 10 mg/kg p.o. It is concluded that BAY 59-3074 may offer a
      valuable therapeutic approach to treat diverse chronic pain conditions.

PMID- 15140914
TI  - Botulinum toxin type A targets RhoB to inhibit lysophosphatidic acid-stimulated
      actin reorganization and acetylcholine release in nerve growth factor-treated
      PC12 cells.
AB  - Botulinum toxin type A (BoNT/A) produced by Clostridium botulinum inhibits Ca2+
      dependent acetylcholine (ACh) release (neuroexocytosis) at peripheral
      neuromuscular junctions, sometimes causing neuromuscular paralysis. This
      inhibitory effect is attributed to its metalloprotease activity to cleave the 25
      kDa synaptosomal-associated protein, which is essential for the exocytotic
      machinery. However, deletion of this protein does not result in a complete block
      of neuroexocytosis, suggesting that botulinum-mediated inhibition may occur via
      another mechanism. Rho GTPases, a class of small GTP-binding proteins (G
      proteins), control actin cytoskeletal organization, thereby regulating a variety
      of cellular functions in various cells, including neuronal cells. We have shown
      that the G protein activator lysophosphatidic acid (LPA) triggered actin
      reorganization followed by Ca2+-dependent ACh release in nerve growth factor
      treated PC12 cells and that BoNT/A blocked both events through degradation of
      RhoB by the proteasome. Overexpression of wild-type RhoB caused actin
      reorganization and enhanced the release of ACh by LPA to overcome toxin's
      inhibitory effect on actin reorganization/exocytosis stimulated by LPA, whereas
      overexpression of a dominant negative RhoB inhibited ACh release, regardless of
      LPA and/or toxin treatment. Finally, a knockdown of the RhoB gene via sequence
      specific, post-transcriptional gene silencing reduced RhoB expression in PC12
      cells, resulting in total inhibition of both actin reorganization and ACh release
      induced by LPA. We conclude that the RhoB signaling pathway regulates ACh release
      via actin cytoskeletal reorganization and that botulinum toxin inhibits
      neuroexocytosis by targeting RhoB pathway.

PMID- 15140915
TI  - Structural features of the botulinum neurotoxin molecule that govern binding and
      transcytosis across polarized human intestinal epithelial cells.
AB  - Experiments were done to help localize the minimum essential domain within the
      botulinum toxin molecule that is necessary for binding and transport across human
      gut epithelial cells. The data demonstrated that the neurotoxin alone, in the
      absence of auxiliary proteins, undergoes transcytosis. The neurotoxin by itself
      was examined in the single chain (unnicked serotype B) and dichain (nicked
      serotype B, nicked serotype A) forms, and all displayed the ability to bind and
      penetrate epithelial barriers. In addition, the single chain and dichain
      molecules were examined in the oxidized and reduced states, and again all forms
      were transported. To further define the minimum essential domain, experiments
      were done with two toxin fragments: 1) the heavy chain, which was derived from
      native toxin, and 2) the carboxy-terminal portion of the heavy chain, which was
      generated by recombinant techniques. Interestingly, both fragments were fully
      competent in crossing epithelial barriers. These data suggest that a polypeptide
      derived from the toxin could be used as a carrier domain to transport other
      molecules across epithelial cells. In related experiments, physiological (i.e.,
      potassium depletion) and pharmacological (i.e., chlorpromazine) manipulations
      were used to implicate clathrin-coated pits/vesicles as the structures
      responsible for endocytosis of toxin.

PMID- 15140916
TI  - Functional selectivity of muscarinic receptor antagonists for inhibition of M3
      mediated phosphoinositide responses in guinea pig urinary bladder and
      submandibular salivary gland.
AB  - Binding and functional affinities of the muscarinic acetylcholine (mACh) receptor
      antagonists darifenacin, tolterodine, oxybutynin, and atropine were assessed in
      Chinese hamster ovary (CHO) cells expressing the human recombinant M2 (CHO-m2) or
      M3 (CHO-m3) receptors, and in guinea pig bladder and submandibular gland. In [N
      methyl-3H]scopolamine methyl chloride binding studies in CHO cells, darifenacin
      displayed selectivity (14.8-fold) for the M3 versus M2 mACh receptor subtype.
      Oxybutynin was nonselective, whereas atropine and tolterodine were weakly M2
      selective (5.1- and 6.6-fold, respectively). Antagonist functional affinity
      estimates were determined by the inhibition of agonist-induced [3H]inositol
      phosphate accumulation in CHO-m3 cells and antagonism of the agonist-induced
      inhibition of forskolin-stimulated cyclic AMP accumulation in CHO-m2 cells.
      Darifenacin was the most M3-selective antagonist (32.4-fold), whereas oxybutynin,
      atropine, and tolterodine exhibited lesser selectivity. Functional affinity
      estimates in guinea pig urinary bladder and submandibular salivary gland using
      indices of phosphoinositide turnover revealed that oxybutynin, darifenacin, and
      tolterodine each displayed selectivity for the response in the bladder, relative
      to that seen in the submandibular gland (9.3-, 7.9-, and 7.4-fold, respectively).
      In contrast, atropine displayed a similar affinity in both tissues. These data
      demonstrate that in bladder, compared with submandibular gland from a single
      species, the mACh receptor antagonists darifenacin, tolterodine, and oxybutynin
      display selectivity to inhibit agonist-mediated phosphoinositide responses. It is
      proposed that both responses are mediated via M3 mACh receptor activation and
      that differential functional affinities displayed by some, but not all,
      antagonists are indicative of the influence of cell background upon the
      pharmacology of the M3 mACh receptor.

PMID- 15140917
TI  - Ethologically based resolution of D2-like dopamine receptor agonist-versus
      antagonist-induced behavioral topography in dopamine- and adenosine 3',5'
      monophosphate-regulated phosphoprotein of 32 kDa "knockout" mutants congenic on
      the C57BL/6 genetic background.
AB  - Given the critical role of dopamine- and adenosine 3',5'-monophosphate-regulated
      phosphoprotein of 32 kDa (DARPP-32) in the regulation of dopaminergic function,
      DARPP-32-null mutant mice congenic on the inbred C57BL/6 strain for 10
      generations were examined phenotypically for their ethogram of responsivity to
      the selective D2-like receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3
      hydroxyphenylethylamine) and the selective D2-like receptor antagonist YM 09151-2
      (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4
      methylaminobenzamide), using procedures that resolve all topographies of behavior
      in the natural repertoire. After vehicle challenge, levels of sniffing and
      rearing seated were reduced in DARPP-32 mutants; the injection procedure seems to
      constitute a "stressor" that reveals phenotypic effects of DARPP-32 deletion not
      apparent under natural conditions. Topographical effects of 0.3 to 10.0 mg/kg RU
      24213, primarily induction of sniffing and ponderous locomotion with accompanying
      reductions in rearing, grooming, sifting and chewing, were not altered to any
      material extent in DARPP-32-null mice. However, topographical effects of 0.005 to
      0.625 mg/kg YM 09151-2, namely, reduction in sniffing, locomotion, rearing,
      grooming, and chewing but not sifting, were essentially absent in DARPP-32
      mutants. Thus, the D2-like receptor agonist-mediated ethogram was essentially
      conserved, whereas major elements of the corresponding D2-like receptor
      antagonist-mediated ethogram were essentially absent in DARPP-32-null mice. This
      suggests some relationship between 1) extent of tonic dopaminergic activation of
      DARPP-32 mechanisms and 2) compensatory mechanisms consequent to the
      developmental absence of DARPP-32, which may emerge to act differentially on
      individual elements of the DARPP-32 system. Critically, the present data indicate
      that phenotypic effects of a given gene deletion using an agonist acting on the
      system disrupted cannot be generalized to a corresponding antagonist, and vice
      versa.

PMID- 15140918
TI  - Antiepileptic drug treatment of nonconvulsive seizures induced by experimental
      focal brain ischemia.
AB  - Nonconvulsive seizures (NCSs) after traumatic and ischemic brain injury are often
      refractory to antiepileptic drug therapy and are associated with a decline in
      patient outcome. We recently characterized an in vivo rat model of focal brain
      ischemia-induced NCS and here sought to evaluate potential pharmacological
      treatments. Electroencephalographic activity was recorded continuously for 24 h
      in freely behaving rats subjected to permanent middle cerebral artery occlusion
      (MCAo). Rats were treated with an antiepileptic drug from one of seven different
      drug classes at ED(50) and 2x ED(50) doses (as reported in other rat seizure
      models), delivered as a single i.v. injection 20 min post-MCAo. Vehicle-treated
      rats (n = 9) had an 89% incidence of NCS with an average number of NCS of 8.6 +/-
      1.9. The latency to onset of NCS was 32.5 +/- 3.4 min post-MCAo with an average
      duration of 49.1 +/- 8.2 s/event. The high doses of ethosuximide, gabapentin, fos
      phenytoin, and valproate significantly reduced the incidence of NCS (11, 14, 14,
      and 38%, respectively), whereas midazolam, phenobarbital, and dextromethorphan
      had no significant effect at either dose. Across treatment groups, there was a
      low but significant correlation between the number of NCS events per animal and
      volume of brain infarction (r = 0.352). Antiepileptic drug therapy that prevented
      the occurrence of NCS also reduced mortality from 26 to 7%. Based on combined
      effects on NCS, infarction, neurological recovery, and mortality, ethosuximide
      and gabapentin were identified as having the best therapeutic profile.

PMID- 15140919
TI  - Multiple reference frames for motion in the primate cerebellum.
AB  - Knowledge of body motion through space is necessary for spatial orientation, self
      motion perception, and postural control. Yet, sensory afferent signals may not
      directly provide such information to the brain. Because motion detected by the
      vestibular end organs is encoded in a head-fixed frame of reference, a coordinate
      transformation is thus required to encode body motion. In this study, we
      investigated whether cerebellar motion-sensitive neurons encode the translation
      of the body through space. We systematically changed both the direction of motion
      relative to the body and the static orientation of the head relative to the
      trunk. The activities of motion-sensitive neurons in the most medial of the deep
      cerebellar nuclei, the rostral fastigial nucleus, were compared with those in the
      brainstem vestibular nuclei. We found a distributed representation of reference
      frames for motion in the rostral fastigial nucleus, in contrast to cells in the
      vestibular nuclei, which primarily encoded motion in a head-fixed reference
      frame. This differential representation of motion-related information implies
      potential differences in the functional roles of these areas.

PMID- 15140921
TI  - Evidence that climbing fibers control an intrinsic spike generator in cerebellar
      Purkinje cells.
AB  - It is well established that the climbing fiber (CF) input to a cerebellar
      Purkinje cell (PC) can exert a controlling influence on the background simple
      spike (SS) activity of the cell, in that repetitive stimulation of CFs causes a
      decrease in SS activity, and removal or inactivation of CFs is followed by a rise
      in activity. In the present study, the effects of inactivation of CFs in the
      short term and longer term (hours) were investigated in anesthetized rats to
      determine how the CFs control the PC SS activity. Inactivation of the CF input to
      a PC was accomplished by either reversibly inactivating with lignocaine or by
      microlesioning the inferior olive. Consistent with previous findings, CF removal
      caused a transformation of the PC firing pattern, with SSs discharging more
      regularly and rising to an exceptionally high level. In cases in which CF
      activity resumed, SS rate declined to control levels within a few seconds.
      However, with sustained CF inactivation (30 min to 5 hr), SS activity continues
      to rise progressively and develops an oscillating firing pattern, consisting of
      alternating bursts of high-frequency discharge at up to 100-150 Hz followed by 10
      20 sec periods of electrical quiescence. No accompanying changes in the threshold
      for evoking SSs via the parallel fibers were seen to accompany the increases in
      tonic SS activity. We conclude that the increase in SS activity that follows CF
      inactivation could be caused by the removal of an inhibitory action that CFs
      exert on the intrinsic pacemaker present in PCs under normal conditions.

PMID- 15140920
TI  - The p75 neurotrophin receptor can induce autophagy and death of cerebellar
      Purkinje neurons.
AB  - The cellular mechanisms underlying Purkinje neuron death in various
      neurodegenerative disorders of the cerebellum are poorly understood. Here we
      investigate an in vitro model of cerebellar neuronal death. We report that
      cerebellar Purkinje neurons, deprived of trophic factors, die by a form of
      programmed cell death distinct from the apoptotic death of neighboring granule
      neurons. Purkinje neuron death was characterized by excessive autophagic
      lysosomal vacuolation. Autophagy and death of Purkinje neurons were inhibited by
      nerve growth factor (NGF) and were activated by NGF-neutralizing antibodies.
      Although treatment with antisense oligonucleotides to the p75 neurotrophin
      receptor (p75ntr) decreased basal survival of cultured cerebellar neurons, p75ntr
      antisense decreased autophagy and completely inhibited death of Purkinje neurons
      induced by trophic factor withdrawal. Moreover, adenoviral expression of a p75ntr
      mutant lacking the ligand-binding domain induced vacuolation and death of
      Purkinje neurons. These results suggest that p75ntr is required for Purkinje
      neuron survival in the presence of trophic support; however, during trophic
      factor withdrawal, p75ntr contributes to Purkinje neuron autophagy and death. The
      autophagic morphology resembles that found in neurodegenerative disorders,
      suggesting a potential role for this pathway in neurological disease.

PMID- 15140922
TI  - A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase
      disrupts ATP generation and alters synaptic function.
AB  - A novel paralytic mutant, nubian, was identified in a behavioral screen for
      conditional temperature-sensitive seizure mutants in Drosophila melanogaster.
      nubian mutants display reduced lifespan, abnormal motor behavior, altered
      synaptic structure, and defective neurotransmitter release. The nubian mutant
      disrupts phosphoglycerate kinase (PGK), an enzyme required for ATP generation in
      the terminal stage of the glycolytic pathway. Consistent with altered ATP
      generation in nubian animals, brain extracts show a threefold reduction in
      resting ATP levels compared with controls. Microarray analysis of nubian mutants
      reveals altered transcription of genes implicated in glucose and lipid
      metabolism. Disruption of ATP generation in nubian animals is accompanied by
      temperature-dependent defects in neuronal activity, with initial seizure
      activity, followed by an activity-dependent loss of synaptic transmission. nubian
      mutants also display structural defects at the synapse, with larger varicosity
      size but normal varicosity number, indicating that these synaptic parameters are
      regulated independently. Both exocytotic (NSF) and endocytotic (dynamin)
      ATPase/GTPase activity are required for normal synaptic transmission. Biochemical
      and physiological analyses indicate that synaptic defects in nubian animals are
      secondary to defective endocytosis, suggesting that endocytotic pathways may be
      generally more sensitive to altered ATP levels than those used for exocytosis.
      Alterations in ATP metabolism likely disrupt similar pathways in humans, because
      PGK deficiency is associated with mental retardation, seizures, and exercise
      intolerance. Given the behavioral similarities between disruptions of PGK
      function in Drosophila and humans, the analysis of nubian animals may reveal
      conserved neuronal responses associated with altered ATP generation within the
      brain.

PMID- 15140924
TI  - Cortical synaptic integration in vivo is disrupted by amyloid-beta plaques.
AB  - The accumulation of amyloid-beta protein into plaques is a characteristic feature
      of Alzheimer's disease. However, the contribution of amyloid-beta plaques to
      neuronal dysfunction is unknown. We compared intracellular recordings from
      neocortical pyramidal neurons in vivo in APP-Sw (Tg2576 transgenic mice
      overexpressing amyloid precursor protein with the Swedish mutation) transgenic
      mice to age-matched nontransgenic cohorts at ages either before or after
      deposition of cortical plaques. We show that the evoked synaptic response of
      neurons to transcallosal stimuli is severely impaired in cortex containing
      substantial plaque accumulation, with an average 2.5-fold greater rate of
      response failure and twofold reduction in response precision compared with age
      matched nontransgenic controls. This effect correlated with the presence of
      amyloid-beta plaques and alterations in neuronal process geometry. Responses of
      neurons in younger APP-Sw animals, before plaque accumulation, were similar to
      those in nontransgenic controls. In all cases, spontaneous membrane potential
      dynamics were similar, suggesting that overall levels of synaptic innervation
      were not affected by plaques. Our results show that plaques disrupt the synchrony
      of convergent inputs, reducing the ability of neurons to successfully integrate
      and propagate information.

PMID- 15140923
TI  - Metabotropic regulation of intrinsic excitability by synaptic activation of
      kainate receptors.
AB  - Prolonged modification of intrinsic neuronal excitability is gaining prominence
      as an activity-dependent form of plasticity. Here we describe a potential
      synaptic initiation mechanism for these changes in which release of the
      transmitter glutamate acts on kainate receptors to regulate the postspike slow
      afterhyperpolarization (sAHP). This action of synaptically released glutamate was
      occluded by previous kainate application. Furthermore, inhibition of glutamate
      uptake enhanced the effects of synaptic activation. Glutamate-mediated kainate
      receptor inhibition of sAHP current (I(sAHP)) was blocked by the PKC inhibitor
      calphostin C, confirming the requirement for a metabotropic signaling cascade.
      These data describe a new physiological function for glutamate release:
      activation of metabotropic kainate receptors, which control directly the
      excitability of pyramidal cells and probably contribute to prolonged excitability
      changes.

PMID- 15140925
TI  - Local sensory cues and place cell directionality: additional evidence of
      prospective coding in the hippocampus.
AB  - In tasks involving goal-directed, stereotyped trajectories on uniform tracks, the
      spatially selective activity of hippocampal principal cells depends on the
      animal's direction of motion. Principal cell ensemble activity while the rat
      moves in opposite directions through a given location is typically uncorrelated.
      It is shown here, with data from three experiments, that multimodal, local
      sensory cues can change the directional properties of CA1 pyramidal cells,
      inducing bidirectionality in a significant proportion of place cells. For a
      majority of these bidirectional place cells, place field centers in the two
      directions of motion were displaced relative to one another, as would be the case
      if the cells were representing a position in space approximately 5-10 cm ahead of
      the rat or if place cells were subject to strong accommodation or inhibition in
      the latter half of their input fields. However, place field density was not
      affected by the presence of local cues, but in the experimental condition with
      the most salient sensory cues, the CA1 population vectors in the "cue-rich"
      condition were sparser and changed more quickly in space than in the "cue-poor"
      condition. These results suggest that "view-invariant" object representations are
      projected to the hippocampus from lower cortical areas and can have the effect of
      increasing the correlation of the hippocampal input vectors in the two
      directions, hence decreasing the orthogonality of hippocampal output.

PMID- 15140926
TI  - Astrocyte glutamate transporters regulate metabotropic glutamate receptor
      mediated excitation of hippocampal interneurons.
AB  - Clearance of extracellular glutamate is essential for limiting the activity of
      metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the
      relative contribution of transporters found in neuronal and glial membranes to
      this uptake is poorly understood. Hippocampal interneurons located at the oriens
      alveus border express mGluR1alpha, a metabotropic glutamate receptor that
      regulates excitability and synaptic plasticity. To determine which glutamate
      transporters are essential for removing glutamate at these excitatory synapses,
      we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM)
      interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably
      elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly
      depolarized to allow Ca2+ entry before stimulation. Selective inhibition of GLT-1
      [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with
      dihydrokainate increased the amplitude of these responses approximately
      threefold, indicating that these transporters compete with mGluRs for
      synaptically released glutamate. However, inhibition of all glutamate
      transporters with TBOA (DL-threo-b-benzyloxyaspartic acid) increased mGluR1 EPSCs
      >15-fold, indicating that additional transporters also shape activation of these
      receptors. To identify these transporters, we examined mGluR1 EPSCs in mice
      lacking GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for
      excitatory amino acid carrier; EAAT3). A comparison of responses recorded from
      wild-type and transporter knock-out mice revealed that the astroglial glutamate
      transporters GLT-1 and GLAST, but not the neuronal transporter EAAC1, restrict
      activation of mGluRs in O-LM interneurons. Transporter-dependent potentiation of
      mGluR1 EPSCs led to a dramatic increase in interneuron firing and enhanced
      inhibition of CA1 pyramidal neurons, suggesting that acute or prolonged
      disruption of transporter activity could lead to changes in network activity as a
      result of enhanced interneuron excitability.

PMID- 15140927
TI  - Functional imaging of working memory after 24 hr of total sleep deprivation.
AB  - The neurobehavioral effects of 24 hr of total sleep deprivation (SD) on working
      memory in young healthy adults was studied using functional magnetic resonance
      imaging. Two tasks, one testing maintenance and the other manipulation and
      maintenance, were used. After SD, response times for both tasks were
      significantly slower. Performance was better preserved in the more complex task.
      Both tasks activated a bilateral, left hemisphere-dominant frontal-parietal
      network of brain regions reflecting the engagement of verbal working memory. In
      both states, manipulation elicited more extensive and bilateral (L>R) frontal,
      parietal, and thalamic activation. After SD, there was reduced blood oxygenation
      level-dependent signal response in the medial parietal region with both tasks.
      Reduced deactivation of the anterior medial frontal and posterior cingulate
      regions was observed with both tasks. Finally, there was disproportionately
      greater activation of the left dorsolateral prefrontal cortex and bilateral
      thalamus when manipulation was required. This pattern of changes in activation
      and deactivation bears similarity to that observed when healthy elderly adults
      perform similar tasks. Our data suggest that reduced activation and reduced
      deactivation could underlie cognitive impairment after SD and that increased
      prefrontal and thalamic activation may represent compensatory adaptations. The
      additional left frontal activation elicited after SD is postulated to be task
      dependent and contingent on task complexity. Our findings provide neural
      correlates to explain why task performance in relatively more complex tasks is
      better preserved relative to simpler ones after SD.

PMID- 15140928
TI  - Noradrenergic inhibition of midbrain dopamine neurons.
AB  - Receptors that couple to phosphoinositide hydrolysis, which include metabotropic
      glutamate receptors (mGluRs) and muscarinic receptors, are known to either
      activate or inhibit the activity of dopamine cells depending on the pattern of
      receptor activation. Transient activation of alpha1 adrenoceptors with
      norepinephrine (NE) resulted in an outward current in midbrain dopamine neurons
      recorded in brain slices. The NE-mediated outward current was induced by
      activation of a potassium conductance through release of calcium from
      intracellular stores. Unlike the mGluR-mediated outward current, the outward
      current induced by alpha1 adrenoceptors often consisted of multiple peaks.
      Activation of alpha1 adrenoceptors also induced a wave of calcium release that
      spread through the soma and proximal dendrites without a decline in amplitude or
      rate of propagation and therefore differed qualitatively from that induced by
      mGluRs. Finally, the alpha1 adrenoceptor-activated outward current was more
      sensitive to the calcium store-depleting agents ryanodine and caffeine. Thus,
      although both alpha1 adrenoceptors and mGluRs mobilize calcium from intracellular
      stores, the mechanisms and pools of calcium differ. The results suggest that
      noradrenergic innervation of dopamine cells can directly inhibit the activity of
      dopamine cells. Psychostimulants, such as amphetamine, will therefore have a
      direct effect on the firing pattern of dopamine neurons through a combination of
      actions on dopamine and alpha1 adrenoceptor activation.

PMID- 15140929
TI  - Neuropathic pain activates the endogenous kappa opioid system in mouse spinal
      cord and induces opioid receptor tolerance.
AB  - Release of endogenous dynorphin opioids within the spinal cord after partial
      sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain
      processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able
      to detect the serine 369 phosphorylated form of the KOR, we determined possible
      sites of dynorphin action within the spinal cord after pSNL. KOR-P
      immunoreactivity (IR) was markedly increased in the L4-L5 spinal dorsal horn of
      wild-type C57BL/6 mice (7-21 d) after lesion, but not in mice pretreated with the
      KOR antagonist nor-binaltorphimine (norBNI). In addition, knock-out mice lacking
      prodynorphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant
      increases in KOR-P IR after pSNL. KOR-P IR was colocalized in both GABAergic
      neurons and GFAP-positive astrocytes in both ipsilateral and contralateral spinal
      dorsal horn. Consistent with sustained opioid release, KOR knock-out mice
      developed significantly increased tactile allodynia and thermal hyperalgesia in
      both the early (first week) and late (third week) interval after lesion.
      Similarly, mice pretreated with norBNI showed enhanced hyperalgesia and allodynia
      during the 3 weeks after pSNL. Because sustained activation of opioid receptors
      might induce tolerance, we measured the antinociceptive effect of the kappa
      agonist U50,488 using radiant heat applied to the ipsilateral hindpaw, and we
      found that agonist potency was significantly decreased 7 d after pSNL. In
      contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance
      after pSNL. These findings suggest that pSNL induced a sustained release of
      endogenous prodynorphin-derived opioid peptides that activated an anti
      nociceptive KOR system in mouse spinal cord. Thus, endogenous dynorphin had both
      pronociceptive and antinociceptive actions after nerve injury and induced GRK3
      mediated opioid tolerance.

PMID- 15140930
TI  - Adult bone marrow stromal cells in the embryonic brain: engraftment, migration,
      differentiation, and long-term survival.
AB  - We recently differentiated adult rat and human bone marrow stromal cells (MSCs)
      into presumptive neurons in cell culture. To determine whether the MSCs assume
      neuronal functions in vivo, we now characterize for the first time engraftment,
      migration, phenotypic expression, and long-term survival after infusion into
      embryonic day 15.5 (E15.5) rat ventricles in utero. By E17.5, donor cells formed
      discrete spheres in periventricular germinal zones, suggesting preferential sites
      of engraftment. The cells expressed progenitor vimentin and nestin but not mature
      neuronal markers. By E19.5, a subset assumed elongated migratory morphologies
      apposed to radial nestin-positive fibers running through the cortical white
      matter and plate, suggesting migration along radial glial processes. Cells
      remaining in germinal zones extended long, vimentin-positive fibers into the
      parenchyma, suggesting that the MSCs generated both migratory neurons and guiding
      radial glia. Consistent with this suggestion, >50% of cultured mouse MSCs
      expressed the neuroprecursor/radial glial protein RC2. From E19.5 to postnatal
      day 3, MSCs populated distant areas, including the neocortices, hippocampi,
      rostral migratory stream, and olfactory bulbs. Whereas donor cells confined to
      the subventricular zone continued to express nestin, cells in the neocortex and
      midbrain expressed mature neuronal markers. The donor cells survived for at least
      2 months postnatally, the longest time examined. Confocal analysis revealed
      survival of thousands of cells per cubic millimeter in the frontal cortex and
      olfactory bulb at 1 month. In the cortex and bulb, 98.6 and 77.3% were NeuN
      (neuronal-specific nuclear protein) positive, respectively. Our observations
      suggest that transplanted adult MSCs differentiate in a regionally and temporally
      specific manner.

PMID- 15140931
TI  - Interaction between perirhinal and medial prefrontal cortex is required for
      temporal order but not recognition memory for objects in rats.
AB  - The present study investigated the roles of the perirhinal cortex, medial
      prefrontal cortex, and intrahemispheric interactions between them in recognition
      and temporal order memory for objects. Experiment 1 assessed the effects of
      bilateral microinfusions of the sodium channel blocker lidocaine into either the
      anterior perirhinal or medial prefrontal cortex immediately before memory testing
      in a familiarity discrimination task and a recency discrimination task, both of
      which involved spontaneous exploration of objects. Inactivation of the perirhinal
      cortex disrupted performance in both tasks, whereas inactivation of the medial
      prefrontal cortex disrupted performance in the recency, but not the familiarity,
      discrimination task. In a second experiment, the importance of intrahemispheric
      interactions between these structures in temporal order memory were assessed by
      comparing the effects of unilateral inactivation of either structure alone with
      those of crossed unilateral inactivation of both structures on the recency
      discrimination task. Crossed unilateral inactivation of both structures produced
      a significant impairment, whereas inactivation of either structure alone produced
      little or no impairment. Collectively, these findings suggest that the perirhinal
      cortex, but not the medial prefrontal cortex, contributes to retrieval of
      information necessary for long-term object recognition, whereas both structures,
      via intrahemispheric interactions between them, contribute to retrieval of
      information necessary for long-term object temporal order memory. These data are
      consistent with models in which attributed information is stored in posterior
      cortical sites and supports lower-order mnemonic functions (e.g., recognition
      memory) but can also be retrieved and further processed via interactions with the
      prefrontal cortex to support higher-order mnemonic functions (e.g., temporal
      order memory).

PMID- 15140932
TI  - Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium
      channels modulated by tetrodotoxin and protease inhibitors.
AB  - We demonstrated previously that dynamic stretch injury of cultured axons induces
      structural changes and Ca2+ influx modulated by tetrodotoxin (TTX)-sensitive
      voltage-gated sodium channels (NaChs). In the present study, we evaluated
      potential damage to the NaCh alpha-subunit, which can cause noninactivation of
      NaChs. In addition, we explored the effects of pre-injury and post-injury
      treatment with TTX and protease inhibition on proteolysis of the NaCh alpha
      subunit and intra-axonal calcium levels ([Ca2+]i) over 60 min after trauma. After
      stretch injury, we found that [Ca2+]i continued to increase in untreated axons
      for at least 60 min. We also observed that the III-IV intra-axonal loop of the
      NaCh alpha-subunit was proteolyzed between 5 and 20 min after trauma. Pre-injury
      treatment of the axons with TTX completely abolished the posttraumatic increase
      in [Ca2+]i and proteolysis of the NaCh alpha-subunit. In addition, both pre
      injury and post-injury inhibition of protease activity attenuated long-term
      increases in [Ca2+]i as well as mitigating degradation of the NaCh alpha-subunit.
      These results suggest a unique "feed-forward" deleterious process initiated by
      mechanical trauma of axons. Na+ influx through NaChs resulting from axonal
      deformation triggers initial increases in [Ca2+]i and subsequent proteolysis of
      the NaCh-subunit. In turn, degradation of the alpha-subunit promotes persistent
      elevations in [Ca2+]i, fueling additional pathologic changes. These observations
      may have important implications for developing therapeutic strategies for axonal
      trauma.

PMID- 15140933
TI  - KCNQ/M channels control spike afterdepolarization and burst generation in
      hippocampal neurons.
AB  - KCNQ channel subunits are widely expressed in peripheral and central neurons,
      where they give rise to a muscarinic-sensitive, subthreshold, and noninactivating
      K+ current (M-current). It is generally agreed that activation of KCNQ/M channels
      contributes to spike frequency adaptation during sustained depolarizations but is
      too slow to influence the repolarization of solitary spikes. This concept,
      however, is based mainly on experiments with muscarinic agonists, the multiple
      effects on membrane conductances of which may overshadow the distinctive effects
      of KCNQ/M channel block. Here, we have used selective modulators of KCNQ/M
      channels to investigate their role in spike electrogenesis in CA1 pyramidal
      cells. Solitary spikes were evoked by brief depolarizing current pulses injected
      into the neurons. The KCNQ/M channel blockers linopirdine and XE991 markedly
      enhanced the spike afterdepolarization (ADP) and, in most neurons, converted
      solitary ("simple") spikes to high-frequency bursts of three to seven spikes
      ("complex" spikes). Conversely, the KCNQ/M channel opener retigabine reduced the
      spike ADP and induced regular firing in bursting neurons. Selective block of BK
      or SK channels had no effect on the spike ADP or firing mode in these neurons. We
      conclude that KCNQ/M channels activate during the spike ADP and limit its
      duration, thereby precluding its escalation to a burst. Consequently, down
      modulation of KCNQ/M channels converts the neuronal firing pattern from simple to
      complex spiking, whereas up-modulation of these channels exerts the opposite
      effect.

PMID- 15140934
TI  - Contribution of AMPA, NMDA, and GABA(A) receptors to temporal pattern of
      postsynaptic responses in the inferior colliculus of the rat.
AB  - The central nucleus of the inferior colliculus (ICC) is a major site of synaptic
      interaction in the central auditory system. To understand how ICC neurons
      integrate excitatory and inhibitory inputs for processing temporal information,
      we examined postsynaptic responses of ICC neurons to repetitive stimulation of
      the lateral lemniscus at 10-100 Hz in rat brain slices. The excitatory synaptic
      currents mediated by AMPA and NMDA receptors and the inhibitory current mediated
      by GABA(A) receptors were pharmacologically isolated and recorded by whole-cell
      patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and
      GABA(A) receptor-mediated IPSCs were similar and much faster than those of NMDA
      receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a
      rate of 10-100 Hz but showed response depression during the course of repetitive
      stimulation. GABA(A) IPSCs could also follow stimulus pulses over this frequency
      range but showed depression at low rates and facilitation at higher rates. NMDA
      EPSCs showed facilitation and temporal summation in response to repetitive
      stimulation, which was most pronounced at higher rates of stimulation. GABA(A)
      inhibition suppressed activation of NMDA receptors and reduced both the degree of
      AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The
      results indicate that GABA(A) receptor-mediated inhibition plays a crucial role
      in maintaining the balance of excitation and inhibition and in allowing ICC
      neurons to process temporal information more precisely.

PMID- 15140935
TI  - Targeted deletion of the kynurenine aminotransferase ii gene reveals a critical
      role of endogenous kynurenic acid in the regulation of synaptic transmission via
      alpha7 nicotinic receptors in the hippocampus.
AB  - It has been postulated that endogenous kynurenic acid (KYNA) modulates alpha7*
      nicotinic acetylcholine receptor (nAChR) and NMDA receptor activities in the
      brain.a To test this hypothesis, alpha7* nAChR and NMDA receptor functions were
      studied in mice with a targeted null mutation in the gene encoding kynurenine
      aminotransferase II (mKat-2-/- mice), an enzyme responsible for brain KYNA
      synthesis. At 21 postnatal days, mKat-2-/- mice had lower hippocampal KYNA levels
      and higher spontaneous locomotor activity than wild-type (WT) mice. At this age,
      alpha7* nAChR activity induced by exogenous application of agonists to CA1
      stratum radiatum interneurons was approximately 65% higher in mKat-2-/- than WT
      mice. Binding studies indicated that the enhanced receptor activity may not have
      resulted from an increase in alpha7* nAChR number. In 21-d-old mKat-2-/- mice,
      endogenous alpha7* nAChR activity in the hippocampus was also increased, leading
      to an enhancement of GABAergic activity impinging onto CA1 pyramidal neurons that
      could be reduced significantly by acute exposure to KYNA (100 nM). The activities
      of GABA(A) and NMDA receptors in the interneurons and of alpha3beta4* nAChRs
      regulating glutamate release onto these neurons were comparable between mKat-2-/-
      and WT mice. By 60 d of age, KYNA levels and GABAergic transmission in the
      hippocampus and locomotor activity were similar between mKat-2-/- and WT mice.
      Our findings that alpha7* nAChRs are major targets for KYNA in the brain may
      provide insights into the pathophysiology of schizophrenia and Alzheimer's
      disease, disorders in which brain KYNA levels are increased and alpha7* nAChR
      functions are impaired.

PMID- 15140936
TI  - The population response of A- and C-fiber nociceptors in monkey encodes high
      intensity mechanical stimuli.
AB  - The peripheral neural mechanism of pain to mechanical stimuli remains elusive. C
      fiber nociceptors do not appear to play a major role in mechanical pain
      sensation, because the stimulus-response function of mechanically sensitive C
      fiber nociceptors to punctate mechanical stimuli applied to the most sensitive
      region in the receptive field (the hot spot) reaches a plateau at force levels
      insufficient to produce pain in humans. However, studies at the hot spot give an
      incomplete understanding of the inputs of nociceptors to the spinal cord. To
      estimate how the population of nociceptors responds to a punctate stimulus, it is
      necessary to know how the response varies with the position within the receptive
      field. For A-fiber and C-fiber nociceptors, we systemically measured the response
      to a 100 microm wide blade stimulus as a function of position in the receptive
      field at different force levels. Highly reproducible receptive field response
      maps that contained multiple peaks and valleys were obtained. Some peaks were
      only 100 microm wide. As force increased, the response and width of the peaks
      increased, the response in valleys increased, and new peaks appeared. The
      averaged response across the map provides an estimate of the population response
      and was found to increase monotonically with force over a large stimulus range
      for both A-fiber and C-fiber nociceptors. These data provide evidence that both C
      fiber and A-fiber nociceptors may encode high-intensity mechanical stimuli.

PMID- 15140937
TI  - Retarded axonal transport of R406W mutant tau in transgenic mice with a
      neurodegenerative tauopathy.
AB  - Intracellular accumulations of filamentous tau inclusions are neuropathological
      hallmarks of neurodegenerative diseases known as tauopathies. The discovery of
      multiple pathogenic tau gene mutations in many kindreds with familial
      frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)
      unequivocally confirmed the central role of tau abnormalities in the etiology of
      neurodegenerative disorders. To examine the effects of tau gene mutations and the
      role of tau abnormalities in neurodegenerative tauopathies, transgenic (Tg) mice
      were engineered to express the longest human tau isoform (T40) with or without
      the R406W mutation (RW and hWT Tg mice, respectively) that is pathogenic for FTDP
      17 in several kindreds. RW but not hWT tau Tg mice developed an age-dependent
      accumulation of insoluble filamentous tau aggregates in neuronal perikarya of the
      cerebral cortex, hippocampus, cerebellum, and spinal cord. Significantly, CNS
      axons in RW mice contained reduced levels of tau when compared with hWT mice, and
      this was linked to retarded axonal transport and increased accumulation of an
      insoluble pool of RW but not hWT tau. Furthermore, RW but not hWT mice
      demonstrated neurodegeneration and a reduced lifespan. These data indicate that
      the R406W mutation causes reduced binding of this mutant tau to microtubules,
      resulting in slower axonal transport. This altered tau function caused by the RW
      mutation leads to increased accumulation and reduced solubility of RW tau in an
      age-dependent manner, culminating in the formation of filamentous intraneuronal
      tau aggregates similar to that observed in tauopathy patients.

PMID- 15140938
TI  - The function of neurotrophic factor receptors expressed by the developing
      adductor motor pool in vivo.
AB  - We examined the spatio-temporal relationship between neurotrophic factor receptor
      (NTF-R) expression and motoneuron (MN) survival in the developing avian spinal
      cord and observed heterogeneity in the expression of NTF-Rs between, but not
      within, pools of MNs projecting to individual muscles. We then focused on the
      role of NTFs in regulating the survival of one motor pool of MNs, all of which
      innervate a pair of adductor muscles in the thigh and hence compete for survival
      during the period of programmed cell death (PCD). The complete NTF-R complement
      of these MNs was analyzed and found to include many, but not all, NTF-Rs.
      Treatment with exogenous individual NTFs rescued some, but not all, adductor MNs
      expressing appropriate NTF-Rs. In contrast, administration of multiple NTFs
      completely rescued adductor MNs from PCD. Additionally, adductor MNs were
      partially rescued from PCD by NTFs for which they failed to express receptors.
      NTF-Rs expressed by the nerve but not in the muscle target were capable of
      mediating survival signals to MNs in trans. Finally, the expression of some NTF
      Rs by adductor MNs was not required for MN survival. These studies demonstrate
      the complexity in NTF regulation of a defined subset of competing MNs and suggest
      that properties other than NTF-R expression itself can play a role in mediating
      trophic responses to NTFs.

PMID- 15140939
TI  - Mechanism of activity-dependent downregulation of the neuron-specific K-Cl
      cotransporter KCC2.
AB  - GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by
      the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained
      interictal-like activity in hippocampal slices downregulates KCC2 mRNA and
      protein expression in CA1 pyramidal neurons, which leads to a reduced capacity
      for neuronal Cl- extrusion. This effect is mediated by endogenous BDNF acting on
      tyrosine receptor kinase B (TrkB), with down-stream cascades involving both
      Shc/FRS-2 (src homology 2 domain containing transforming protein/FGF receptor
      substrate 2) and PLCgamma (phospholipase Cgamma)-cAMP response element-binding
      protein signaling. The plasmalemmal KCC2 has a very high rate of turnover, with a
      time frame that suggests a novel role for changes in KCC2 expression in diverse
      manifestations of neuronal plasticity. A downregulation of KCC2 may be a general
      early response involved in various kinds of neuronal trauma.

PMID- 15140940
TI  - Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human
      amyloid precursor protein transgenic mice.
AB  - Alzheimer's disease (AD), the most common neurodegenerative disorder, results in
      progressive degeneration of synapses and aberrant sprouting of axon terminals.
      The mechanisms underlying these seemingly opposing cellular phenomena are
      unclear. We hypothesized that Fyn kinase may play a role in one or both of these
      processes because it is increased in AD brains and because it is involved in
      synaptic plasticity and axonal outgrowth. We investigated the effects of Fyn on
      AD-related synaptotoxicity and aberrant axonal sprouting by ablating or
      overexpressing Fyn in human amyloid precursor protein (hAPP) transgenic mice. On
      the fyn+/+ background, hAPP/amyloid beta peptide (Abeta) decreased hippocampal
      levels of synaptophysin-immunoreactive presynaptic terminals (SIPTs), consistent
      with previous findings. On the fyn-/- background, hAPP/Abeta did not affect
      SIPTs. SIPT reductions correlated with hippocampal Abeta levels in hAPP/fyn+/+,
      but not hAPP/fyn-/-, mice suggesting that Fyn provides a critical link between
      hAPP/Abeta and SIPTs. Furthermore, overexpression of Fyn exacerbated SIPT
      reductions in hAPP mice. We also found that the susceptibility of mice to
      hAPP/Abeta-induced premature mortality was decreased by Fyn ablation and
      increased by Fyn overexpression. In contrast, axonal sprouting in the hippocampus
      of hAPP mice was unaffected. We conclude that Fyn-dependent pathways are critical
      in AD-related synaptotoxicity and that the pathogenesis of hAPP/Abeta-induced
      neuronal alterations may be mechanistically heterogenous.

PMID- 15140941
TI  - Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2
      (L-type) Ca2+ channels.
AB  - Ca2+-binding protein-1 (CaBP1) is a Ca2+-binding protein that is closely related
      to calmodulin (CaM) and localized in somatodendritic regions of principal neurons
      throughout the brain, but how CaBP1 participates in postsynaptic Ca2+ signaling
      is not known. Here, we describe a novel role for CaBP1 in the regulation of Ca2+
      influx through Ca(v)1.2 (L-type) Ca2+ channels. CaBP1 interacts directly with the
      alpha1 subunit of Ca(v)1.2 at sites that also bind CaM. CaBP1 binding to one of
      these sites, the IQ domain, is Ca2+ dependent and competitive with CaM binding.
      The physiological significance of this interaction is supported by the
      association of Ca(v)1.2 and CaBP1 in postsynaptic density fractions purified from
      rat brain. Moreover, in double-label immunofluorescence experiments, CaBP1 and
      Ca(v)1.2 colocalize in numerous cell bodies and dendrites of neurons,
      particularly in pyramidal cells in the CA3 region of the hippocampus and in the
      dorsal cortex. In electrophysiological recordings of cells transfected with
      Ca(v)1.2, CaBP1 greatly prolonged Ca2+ currents, prevented Ca2+-dependent
      inactivation, and caused Ca2+-dependent facilitation of currents evoked by step
      depolarizations and repetitive stimuli. These effects contrast with those of CaM,
      which promoted strong Ca2+-dependent inactivation of Ca(v)1.2 with these same
      voltage protocols. Our findings reveal how Ca2+-binding proteins, such as CaM and
      CaBP1, differentially adjust Ca2+ influx through Ca(v)1.2 channels, which may
      specify diverse modes of Ca2+ signaling in neurons.

PMID- 15140942
TI  - E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and
      apoptosis.
AB  - The p53 tumor suppressor protein is phosphorylated and activated by several DNA
      damage-inducible kinases, such as ATM, and is a key effector of the DNA damage
      response by promoting cell cycle arrest or apoptosis. Deregulation of the Rb-E2F1
      pathway also results in the activation of p53 and the promotion of apoptosis, and
      this contributes to the suppression of tumor development. Here, we describe a
      novel connection between E2F1 and the ATM DNA damage response pathway. In primary
      human fibroblasts lacking functional ATM, the ability of E2F1 to induce the
      phosphorylation of p53 and apoptosis is impaired. In contrast, ATM status has no
      effect on transcriptional activation of target genes or the stimulation of DNA
      synthesis by E2F1. Cells containing mutant Nijmegen breakage syndrome protein
      (NBS1), a component of the Mre11-Rad50 DNA repair complex, also have attenuated
      p53 phosphorylation and apoptosis in response to E2F1 expression. Moreover, E2F1
      induces ATM- and NBS1-dependent phosphorylation of the checkpoint kinase Chk2 at
      Thr68, a phosphorylation site that stimulates Chk2 activity. Delayed gammaH2AX
      phosphorylation and absence of ATM autophosphorylation at Ser1981 suggest that
      E2F1 stimulates ATM through a unique mechanism that is distinct from agents that
      cause DNA double-strand breaks. These findings identify new roles for several DNA
      damage response factors by demonstrating that they also participate in the
      oncogenic stress signaling pathway between E2F1 and p53.

PMID- 15140943
TI  - Enhanced growth of pancreatic tumors in SPARC-null mice is associated with
      decreased deposition of extracellular matrix and reduced tumor cell apoptosis.
AB  - SPARC, a matricellular glycoprotein, modulates cellular interaction with the
      extracellular matrix (ECM). Tumor growth and metastasis occur in the context of
      the ECM, the levels and deposition of which are controlled in part by SPARC.
      Tumor-derived SPARC is reported to stimulate or retard tumor progression
      depending on the tumor type, whereas the function of host-derived SPARC in
      tumorigenesis has not been explored fully. To evaluate the function of endogenous
      SPARC, we have examined the growth of pancreatic tumors in SPARC-null (SP(-/-))
      mice and their wild-type (SP(+/+)) counterparts. Mouse pancreatic adenocarcinoma
      cells injected s.c. grew significantly faster in SP(-/-) mice than cells injected
      into SP(+/+) animals, with mean tumor weights at sacrifice of 0.415 +/- 0.08 and
      0.086 +/- 0.03 g (P < 0.01), respectively. Lack of endogenous SPARC resulted in
      decreased collagen deposition and fiber formation, alterations in the
      distribution of tumor-infiltrating macrophages, and decreased tumor cell
      apoptosis. There was no difference in microvessel density of tumors from SP(-/-)
      or SP(+/+) mice. However, tumors grown in SP(-/-) had a lower percentage of blood
      vessels that expressed smooth muscle alpha-actin, a marker of pericytes. These
      data reflect the importance of ECM deposition in regulating tumor growth and
      demonstrate that host-derived SPARC is a critical factor in the response of host
      tissue to tumorigenesis.

PMID- 15140944
TI  - Epidermal growth factor modulates tyrosine phosphorylation of a novel tensin
      family member, tensin3.
AB  - Here, we report the identification of a new tensin family member, tensin3, and
      its role in epidermal growth factor (EGF) signaling pathway. Human tensin3 cDNA
      encodes a 1445 amino acid sequence that shares extensive homology with tensin1,
      tensin2, and COOH-terminal tensin-like protein. Tensin3 is expressed in various
      tissues and in different cell types such as endothelia, epithelia, and
      fibroblasts. The potential role of tensin3 in EGF-induced signaling pathway is
      explored. EGF induces tyrosine phosphorylation of tensin3 in MDA-MB-468 cells in
      a time- and dose-dependent manner, but it is independent of an intact actin
      cytoskeleton or phosphatidylinositol 3-kinase. Activation of EGF receptor is
      necessary but not sufficient for tyrosine phosphorylation of tensin3. It also
      requires Src family kinase activities. Furthermore, tensin3 forms a complex with
      focal adhesion kinase and p130Cas in MDA-MB-468 cells. Addition of EGF to the
      cells induces dephosphorylation of these two molecules, leads to disassociation
      of the tensin3-focal adhesion kinase-p130Cas complex, and enhances the
      interaction between tensin3 and EGF receptor. Our results demonstrate that
      tensin3 may function as a platform for the disassembly of EGF-related signaling
      complexes at focal adhesions.

PMID- 15140945
TI  - Raf and RhoA cooperate to transform intestinal epithelial cells and induce growth
      resistance to transforming growth factor beta.
AB  - Although unregulated activation of the Ras/Raf/mitogen-activated protein kinase
      kinase/Erk signaling pathway is believed to be a central mechanism by which many
      cell types undergo oncogenic transformation, recent studies indicate that
      activation of Raf kinase by oncogenic Ras is not sufficient to cause tumorigenic
      transformation in intestinal epithelial cells. Thus, identification of signaling
      proteins and pathways that interact with Raf to transform intestinal epithelial
      cells may be critical for understanding aberrant growth control in the intestinal
      epithelium. Functional interactions between Raf and the small GTPase RhoA were
      studied in RIE-1 cells overexpressing both activated Raf(22W) and activated
      RhoA(63L). Double transfectants were morphologically transformed, formed colonies
      in soft agar, grew in nude mice, overexpressed cyclin D1 and cyclooxygenase-2
      (COX-2), and were resistant to growth inhibition by transforming growth factor
      (TGF) beta. RIE-Raf and RIE-RhoA single transfectants showed none of these
      characteristics. Expression of a dominant-negative RhoA(N19) construct in RIE
      Ras(12V) cells was associated with markedly reduced COX-2 mRNA, COX-2 protein,
      and prostaglandin E2 levels when compared with RIE-Ras(12V) cells transfected
      with vector alone. However, no change in transformed morphology, growth in soft
      agar, cyclin D1 expression, TGFalpha expression, or TGFbeta sensitivity was
      observed. In summary, coexpression of activated Raf and RhoA induces
      transformation and TGFbeta resistance in intestinal epithelial cells. Although
      blockade of RhoA signaling reverses certain well-described characteristics of RIE
      Ras cells, it is insufficient to reverse the transformed phenotype and restore
      TGFbeta sensitivity. Blockade of additional Rho family members or alternate Ras
      effector pathways may be necessary to fully reverse the Ras phenotype.

PMID- 15140946
TI  - Multiple aspects of the phenotype of mammary epithelial cells transformed by
      expression of activated M-Ras depend on an autocrine mechanism mediated by
      hepatocyte growth factor/scatter factor.
AB  - Multiple aspects of the transformed phenotype induced in a murine mammary
      epithelial cell line scp-2 by expression of activated G22V M-Ras, including
      maintainance of cell number at low density, anchorage-independent growth,
      invasion of Matrigel, and secretion of matrix metalloproteinases (MMP) 2 and 9,
      were dependent on an autocrine mechanism. Conditioned medium from dense cultures
      of scp-2 cells expressing G22V M-Ras, but not from parental cells, induced
      activation of Erk and Akt in cells expressing G22V M-Ras, maintained the cell
      number and promoted anchorage-independent growth of cells expressing G22V M-Ras
      (although not the parental cells), and induced scattering of MDCK cells. The
      latter activities were blocked by neutralizing antibodies to hepatocyte growth
      factor/scatter factor (HGF/SF) and could be mimicked by HGF/SF. Anti-HGF/SF
      antibodies also inhibited invasion of Matrigel, and the production of MMP-2 and
      MMP-9, together with urokinase-type plasminogen activator, was secreted by G22V M
      Ras scp-2 cells but not by parental cells. Invasion of Matrigel was blocked by an
      inhibitor of MMPs, BB94, and by the mitogen-activated protein kinase kinase 1/2
      kinase inhibitor PD98059 but was only marginally affected by the
      phosphatidylinositol 3-kinase inhibitor LY294002. Autocrine HGF/SF was thus
      critical for expression of key features of the phenotype of mammary epithelial
      cells transformed by expression of activated M-Ras.

PMID- 15140947
TI  - An assessment of accuracy, error, and conflict with support values from genome
      scale phylogenetic data.
AB  - Despite the importance of molecular phylogenetics, few of its assumptions have
      been tested with real data. It is commonly assumed that nonparametric bootstrap
      values are an underestimate of the actual support, Bayesian posterior
      probabilities are an overestimate of the actual support, and among-gene
      phylogenetic conflict is low. We directly tested these assumptions by using a
      well-supported yeast reference tree. We found that bootstrap values were not
      significantly different from accuracy. Bayesian support values were, however,
      significant overestimates of accuracy but still had low false-positive error
      rates (0% to 2.8%) at the highest values (>99%). Although we found evidence for a
      branch-length bias contributing to conflict, there was little evidence for
      widespread, strongly supported among-gene conflict from bootstraps. The results
      demonstrate that caution is warranted concerning conclusions of conflict based on
      the assumption of underestimation for support values in real data.

PMID- 15140948
TI  - Male-biased mutation rate and divergence in autosomal, z-linked and w-linked
      introns of chicken and Turkey.
AB  - To investigate mutation-rate variation between autosomes and sex chromosomes in
      the avian genome, we have analyzed divergence between chicken (Gallus gallus) and
      turkey (Meleagris galopavo) sequences from 33 autosomal, 28 Z-linked, and 14 W
      linked introns with a total ungapped alignment length of approximately 43,000 bp.
      There are pronounced differences in the mean divergence among autosomes and sex
      chromosomes (autosomes [A] = 10.08%, Z chromosome = 10.99%, and W chromosome =
      5.74%), and we use these data to estimate the male-to-female mutation-rate ratio
      (alpha(m)) from Z/A, Z/W, and A/W comparisons at 1.71, 2.37, and 2.52,
      respectively. Because the alpha(m) estimates of the three comparisons do not
      differ significantly, we find no statistical support for a specific reduction in
      the Z chromosome mutation rate (Z reduction estimated at 4.89%, P = 0.286). The
      idea of mutation-rate reduction in the sex chromosome hemizygous in one sex
      (i.e., X in mammals, Z in birds) has been suggested on the basis of theory on
      adaptive mutation-rate evolution. If it exists in birds, the effect would, thus,
      seem to be weak; a preliminary power analysis suggests that it is significantly
      less than 18%. Because divergence may vary within chromosomal classes as a result
      of variation in mutation and/or selection, we developed a novel double
      bootstrapping method, bootstrapping both by introns and sites from concatenated
      alignments, to estimate confidence intervals for chromosomal class rates and for
      alpha(m). The narrowest interval for the alpha(m) estimate is 1.88 to 2.97 from
      the Z/W comparison. We also estimated alpha(m) using maximum likelihood on data
      from all three chromosome classes; this method yielded alpha(m) = 2.47 and
      approximate 95% confidence intervals of 2.27 to 2.68. Our data are broadly
      consistent with the idea that mutation-rate differences between chromosomal
      classes can be explained by the male mutation bias alone.

PMID- 15140949
TI  - A universal evolutionary index for amino acid changes.
AB  - Different nonsynonymous changes may be under different selective pressure during
      evolution. Of the 190 possible interchanges among the 20 amino acids, only 75 can
      be attained by a single-base substitution. An evolutionary index (EI) can be
      empirically computed for each of the 75 elementary changes as the likelihood of
      substitutions, relative to that of synonymous changes. We used 280, 1,306, 2,488,
      and 309 orthologous genes from primates (human versus Old World monkey), rodents
      (mouse versus rat), yeast (S. cerevisiae versus S. paradoxus), and Drosophila (D.
      melanogaster versus D. simulans), respectively, to estimate the EIs. In each data
      set, EI varies more than 10-fold, and the correlation coefficients of EIs from
      the pairwise comparisons are high (e.g., r = 0.91 between rodent and yeast). The
      high correlations suggest that the amino acid properties are strong determinants
      of protein evolution, irrespective of the identities of the proteins or the taxa
      of interest. However, these properties are not well captured in conventional
      measures of amino acid exchangeability. We, therefore, propose a universal index
      of exchange (U): for any large data set, its EI can be expressed as U*R, where R
      is the average Ka/Ks for that data set. The codon-based, empirically determined
      EI (i.e., U*R) makes much better predictions on protein evolution than do
      previous methods.

PMID- 15140950
TI  - Memory CD8 T-cell differentiation during viral infection.

PMID- 15140951
TI  - Nuclear translocation of papillomavirus minor capsid protein L2 requires Hsc70.
AB  - Minor capsid protein L2 of papillomaviruses plays an essential role in virus
      assembly by recruiting viral components to PML bodies, the proposed sites of
      virus morphogenesis. We demonstrate here that the function of L2 in virus
      assembly requires the chaperone Hsc70. Hsc70 was found dispersed in naturally
      infected keratinocytes and cultured cells. A dramatic relocation of Hsc70 from
      the cytoplasm to PML bodies was induced in these cells by L2 expression. Hsc70-L2
      complex formation was confirmed by coimmunoprecipitation. The complex was
      modulated by the cochaperones Hip and Bag-1, which stabilize and destabilize
      Hsc70-substrate complexes, respectively. Cytoplasmic depletion of Hsc70 caused
      retention of wild-type and N-terminally truncated L2, but not of C-terminally
      truncated L2, in the cytoplasm. This retention was partially reversed by
      overexpression of Hsc70 fused to green fluorescent protein but not by ATPase
      negative Hsc70. Hsc70 associated with L1-L2 virus-like particles (VLPs) but not
      with VLPs composed either of L1 alone or of L1 and C-terminally truncated L2.
      Moreover, displacement of Hsc70 from L1-L2 VLPs by encapsidation of DNA,
      generating pseudovirions, was found. These data indicate that Hsc70 transiently
      associates with viral capsids during the integration of L2, possibly via the L2 C
      terminus. Completion of virus assembly results in displacement of Hsc70 from
      virions.

PMID- 15140952
TI  - Context-dependent effects of L domains and ubiquitination on viral budding.
AB  - Many enveloped viruses encode late assembly domains, or L domains, that
      facilitate virion egress. PTAP-type L domains act by recruiting the ESCRT-I
      (endosomal sorting complex required for transport I) component Tsg101, and
      YPXL/LXXLF-type L domains recruit AIP-1/ALIX, both of which are class E vacuolar
      protein sorting (VPS) factors, normally required for the generation of vesicles
      within endosomes. The binding cofactors for PPXY-type L domains have not been
      unambiguously resolved but may include Nedd4-like ubiquitin ligases. Largely
      because they act as autonomous binding sites for host factors, L domains are
      generally transferable and active in a context-independent manner. Ebola virus
      matrix protein (EbVP40) contains two overlapping L-domain motifs within the
      sequence ILPTAPPEYMEA. Here, we show that both motifs are required for efficient
      EbVP40 budding. However, upon transplantation into two different retroviral
      contexts, the relative contributions of the PTAP and PPEY motifs differ markedly.
      In a murine leukemia virus carrying the EbVP40 sequence, both motifs contributed
      to overall L domain activity, and budding proceeded in a partly Tsg101
      independent manner. Conversely, when transplanted into the context of human
      immunodeficiency virus type 1 (HIV-1), EbVP40 L-domain activity was entirely due
      to a PTAP-Tsg101 interaction. In fact, a number of PPXY-type L domains were
      inactive in the context of HIV-1. Surprisingly, PTAP and YPXL-type L domains that
      simulated HIV-1 budding reduced the amount of ubiquitin conjugated to Gag, while
      inactive PPXY-type L domains increased Gag ubiquitination. These observations
      suggest that active L domains recruit deubiquitinating enzymes as a consequence
      of class E VPS factor recruitment. Moreover, context-dependent L-domain function
      may reflect distinct requirements for host functions during the morphogenesis of
      different viral particles or the underlying presence of additional, as yet
      undiscovered L domains.

PMID- 15140953
TI  - Conformational changes in the nuclear lamina induced by herpes simplex virus type
      1 require genes U(L)31 and U(L)34.
AB  - The herpes simplex virus type 1 (HSV-1) U(L)31 and U(L)34 proteins are dependent
      on each other for proper targeting to the nuclear membrane and are required for
      efficient envelopment of nucleocapsids at the inner nuclear membrane. In this
      work, we show that whereas the solubility of lamins A and C (lamin A/C) was not
      markedly increased, HSV induced conformational changes in the nuclear lamina of
      infected cells, as viewed after staining with three different lamin A/C-specific
      antibodies. In one case, reactivity with a monoclonal antibody that recognizes an
      epitope in the lamin tail domain was greatly reduced in HSV-infected cells. This
      apparent HSV-induced epitope masking required both U(L)31 and U(L)34, but these
      proteins were not sufficient to mask the epitope in uninfected cells, indicating
      that other HSV proteins are also required. In the second case, staining with a
      rabbit polyclonal antibody that primarily recognizes epitopes in the lamin A/C
      rod domain revealed that U(L)34 is required for HSV-induced decreased
      availability of epitopes for reaction with the antibody, whereas U(L)31 protein
      was dispensable for this effect. Still another polyclonal antibody indicated
      virtually no difference in lamin A/C staining in infected versus uninfected
      cells, indicating that the HSV-induced changes are more conformational than the
      result of lamin depletion at the nuclear rim. Further evidence supporting an
      interaction between the nuclear lamina and the U(L)31/U(L)34 protein complex
      includes the observations that (i) overexpression of the U(L)31 protein in
      uninfected cells was sufficient to relocalize lamin A/C from the nuclear rim into
      nucleoplasmic aggregates, (ii) overexpression of U(L)34 was sufficient to
      relocalize some lamin A/C into the cytoplasm, and (iii) both U(L)31 and U(L)34
      could directly bind lamin A/C in vitro. These studies suggest that the U(L)31 and
      U(L)34 proteins modify the conformation of the nuclear lamina in infected cells,
      possibly by direct interaction with lamin A/C, and that other proteins are also
      likely involved. Given that the nuclear lamina potentially excludes nucleocapsids
      from envelopment sites at the inner nuclear membrane, the lamina alteration may
      reflect a role of the U(L)31/U(L)34 protein complex in perturbing the lamina to
      promote nucleocapsid egress from the nucleus. Alternatively, the data are
      compatible with a role of the lamina in targeting the U(L)31/U(L)34 protein
      complex to the nuclear membrane.

PMID- 15140954
TI  - Influenza B virus requires BM2 protein for replication.
AB  - The BM2 protein of influenza B virus functions as an ion channel, which is
      suggested to be important for virus uncoating in endosomes of virus-infected
      cells. Because direct support for this function is lacking, whether BM2 plays an
      essential role in the viral life cycle remains unknown. We therefore attempted to
      generate BM2 knockout viruses by reverse genetics. Mutant viruses possessing M
      segments with the mutated initiation codon of BM2 protein at the stop-start
      pentanucleotide were viable and still expressed BM2. The introduction of multiple
      stop codons and a one-nucleotide deletion downstream of the stop-start
      pentanucleotide, in addition to disablement of the BM2 initiation codon, failed
      to generate viable mutant viruses, but the mutant M segments still expressed
      proteins that reacted with the BM2 peptide antiserum. To completely abolish BM2
      expression, we generated a mutant M gene whose BM2 open reading frame was
      deleted. Although this mutant was not able to replicate in normal MDCK cells, it
      did replicate in a cell line that we established which constitutively expresses
      BM2. Furthermore, a virus possessing the mutant M gene lacking the BM2 open
      reading frame and a mutant NA gene containing the BM2 open reading frame instead
      of the NA open reading frame underwent multiple cycles of replication in MDCK
      cells, with exogenous sialidase used to supplement the deleted viral sialidase
      activity. These findings demonstrate that the BM2 protein is essential for
      influenza B virus replication.

PMID- 15140955
TI  - Fatal disseminated mouse adenovirus type 1 infection in mice lacking B cells or
      Bruton's tyrosine kinase.
AB  - Mouse adenovirus type 1 (MAV-1) infection of B-cell-deficient and Bruton's
      tyrosine kinase (Btk)-deficient mice resulted in fatal disseminated disease
      resembling human adenovirus infections in immunocompromised patients. Mice
      lacking B cells or Btk were highly susceptible to acute MAV-1 infection, in
      contrast to controls and mice lacking T cells. To our knowledge, this is the
      first demonstration that mice with an X-linked immunodeficiency phenotype (Btk
      deficient) are susceptible to virus-induced disease. Mice lacking B cells or Btk
      on a C57BL/6 background succumbed with encephalomyelitis, hepatitis, and lymphoid
      necrosis. Mice lacking B cells on a BALB/c background succumbed with enteritis
      and hepatitis. Survival of acute MAV-1 infection correlated with early T-cell
      independent neutralizing antibody and T-cell-independent antiviral immunoglobulin
      M. Treatment of MAV-1-infected Btk(-/-) mice 4 to 9 days postinfection with
      antiserum harvested 6 to 9 days postinfection from MAV-1-infected Btk(+/+) mice
      was therapeutic. Our findings implicate a critical role for B-cell function in
      preventing disseminated MAV-1 infection, particularly production of early T-cell
      independent antiviral immunoglobulin M.

PMID- 15140956
TI  - Herpes simplex virus 1 U(L)31 and U(L)34 gene products promote the late
      maturation of viral replication compartments to the nuclear periphery.
AB  - Herpes simplex virus 1 (HSV-1) forms replication compartments (RCs), domains in
      which viral DNA replication, late-gene transcription, and encapsidation take
      place, in the host cell nucleus. The formation of these domains leads to
      compression and marginalization of host cell chromatin, which forms a dense layer
      surrounding the viral RCs and constitutes a potential barrier to viral nuclear
      egress or primary envelopment at the inner nuclear membrane. Surrounding the
      chromatin layer is the nuclear lamina, a further host cell barrier to egress. In
      this study, we describe an additional phase in RC maturation that involves
      disruption of the host chromatin and nuclear lamina so that the RC can approach
      the nuclear envelope. During this phase, the structure of the chromatin layer is
      altered so that it no longer forms a continuous layer around the RCs but instead
      is fragmented, forming islands between which RCs extend to reach the nuclear
      periphery. Coincident with these changes, the nuclear lamina components lamin A/C
      and lamin-associated protein 2 appear to be redistributed via a mechanism
      involving the U(L)31 and U(L)34 gene products. Viruses in which the U(L)31 or
      U(L)34 gene has been deleted are unable to undergo this phase of chromatin
      reorganization and lamina alterations and instead form RCs which are bounded by
      an intact host cell chromatin layer and nuclear lamina. We postulate that these
      defects in chromatin restructuring and lamina reorganization explain the
      previously documented growth defects of these mutant viruses.

PMID- 15140957
TI  - Parvovirus infection of cells by using variants of the feline transferrin
      receptor altering clathrin-mediated endocytosis, membrane domain localization,
      and capsid-binding domains.
AB  - The feline and canine transferrin receptors (TfRs) bind canine parvovirus to host
      cells and mediate rapid capsid uptake and infection. The TfR and its ligand
      transferrin have well-described pathways of endocytosis and recycling. Here we
      tested several receptor-dependent steps in infection for their role in virus
      infection of cells. Deletions of cytoplasmic sequences or mutations of the Tyr
      Thr-Arg-Phe internalization motif reduced the rate of receptor uptake from the
      cell surface, while polar residues introduced into the transmembrane sequence
      resulted in increased degradation of transferrin. However, the mutant receptors
      still mediated efficient virus infection. In contrast, replacing the cytoplasmic
      and transmembrane sequences of the feline TfR with those of the influenza virus
      neuraminidase (NA) resulted in a receptor that bound and endocytosed the capsid
      but did not mediate viral infection. This chimeric receptor became localized to
      detergent-insoluble membrane domains. To test the effect of structural virus
      receptor interaction on infection, two chimeric receptors were prepared which
      contained antibody-variable domains that bound the capsid in place of the TfR
      ectodomain. These chimeric receptors bound CPV capsids and mediated uptake but
      did not result in cell infection. Adding soluble feline TfR ectodomain to the
      virus during that uptake did not allow infection.

PMID- 15140958
TI  - T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike
      protein elicit a specific T-cell immune response in patients who recover from
      SARS.
AB  - The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the
      Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus
      strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune
      response in donors who had fully recovered from SARS-CoV infection. We employed
      online database analysis to compare the differences in the amino acid sequences
      of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell
      epitope peptides were synthesized, and their binding affinities for HLA-A2 were
      validated and compared in the T2 cell system. The immunogenicity of all these
      peptides was assessed by using T cells obtained from donors who had fully
      recovered from SARS-CoV infection and from healthy donors with no history of SARS
      CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining
      showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online
      database analysis and the T2 cell binding test disclosed that the number of HLA
      A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or
      even lost in comparison with the homologous sequences of the S protein of HCoV
      229e. Among the peptides used in the study, the affinity of peptides from HCoV
      229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to
      HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-gamma)
      release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and
      S978 induced a high frequency of IFN-gamma-secreting T-cell response in HLA-A2(+)
      donors who had fully recovered from SARS-CoV infection; such a T-cell epitope
      specific response was not observed in HLA-A2(+) healthy donors or in HLA-A2(-)
      donors who had been infected with SARS-CoV after full recovery. Thus, T-cell
      epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell
      response in HLA-A2(+) SARS-CoV-infected patients.

PMID- 15140959
TI  - Multiple enzymatic activities associated with severe acute respiratory syndrome
      coronavirus helicase.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified
      group 2 coronavirus, is the causative agent of severe acute respiratory syndrome,
      a life-threatening form of pneumonia in humans. Coronavirus replication and
      transcription are highly specialized processes of cytoplasmic RNA synthesis that
      localize to virus-induced membrane structures and were recently proposed to
      involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase,
      helicase, and protease activities, also involves a series of RNA-processing
      enzymes that are not found in most other RNA virus families. Here, we
      characterized the enzymatic activities of a recombinant form of the SARS-CoV
      helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N
      terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex
      unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5'-to-3'
      direction and features a remarkable processivity, allowing efficient strand
      separation of extended regions of double-stranded RNA and DNA. Characterization
      of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities
      revealed that all natural nucleotides and deoxynucleotides are substrates of
      nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than
      other nucleotides. Furthermore, we established an RNA 5'-triphosphatase activity
      for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5'
      cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5'
      triphosphatase activities of nsp13 have a common active site. Finally, we
      established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to
      membranes that appear to be derived from the endoplasmic reticulum and are the
      likely site of SARS-CoV RNA synthesis.

PMID- 15140960
TI  - Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1
      activation from the cytoplasmic and nuclear compartments, respectively.
AB  - In previous reports it was demonstrated that the Nipah virus V and W proteins
      have interferon (IFN) antagonist activity due to their ability to block signaling
      from the IFN-alpha/beta receptor (J. J. Rodriguez, J. P. Parisien, and C. M.
      Horvath, J. Virol. 76:11476-11483, 2002; M. S. Park et al., J. Virol. 77:1501
      1511, 2003). The V, W, and P proteins are all encoded by the same viral gene and
      share an identical 407-amino-acid N-terminal region but have distinct C-terminal
      sequences. We now show that the P protein also has anti-IFN function, confirming
      that the common N-terminal domain is responsible for the antagonist activity.
      Truncation of this N-terminal domain revealed that amino acids 50 to 150 retain
      the ability to block IFN and to bind STAT1, a key component of the IFN signaling
      pathway. Subcellular localization studies demonstrate that the V and P proteins
      are predominantly cytoplasmic whereas the W protein is localized to the nucleus.
      In all cases, STAT1 colocalizes with the corresponding Nipah virus protein. These
      interactions are sufficient to inhibit STAT1 activation, as demonstrated by the
      lack of STAT1 phosphorylation on tyrosine 701 in IFN-stimulated cells expressing
      P, V, or W. Therefore, despite their common STAT1-binding domain, the Nipah virus
      V and P proteins act by retaining STAT1 in the cytoplasm while the W protein
      sequesters STAT1 in the nucleus, creating both a cytoplasmic and a nuclear block
      for STAT1. We also show that the IFN antagonist activity of the P protein is not
      as strong as that of V or W, perhaps explaining why Nipah virus has evolved to
      express these two edited products.

PMID- 15140961
TI  - pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated
      by the spike glycoprotein and enhanced by dendritic cell transfer through DC
      SIGN.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several
      putative viral envelope proteins, including the spike (S), membrane (M), and
      small envelope (E) glycoproteins. Although these proteins likely are essential
      for viral replication, their specific roles in SARS-CoV entry have not been
      defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral
      entry through pH-dependent endocytosis. Further, we define its cellular tropism
      and demonstrate that virus transmission occurs through cell-mediated transfer by
      dendritic cells. The S glycoprotein was used successfully to pseudotype
      replication-defective retroviral and lentiviral vectors that readily infected
      Vero cells as well as primary pulmonary and renal epithelial cells from human,
      nonhuman primate, and, to a lesser extent, feline species. The tropism of this
      reporter virus was similar to that of wild-type, replication-competent SARS-CoV,
      and binding of purified S to susceptible target cells was demonstrated by flow
      cytometry. Although myeloid dendritic cells were able to interact with S and to
      bind virus, these cells could not be infected by SARS-CoV. However, these cells
      were able to transfer the virus to susceptible target cells through a synapse
      like structure. Both cell-mediated infection and direct infection were inhibited
      by anti-S antisera, indicating that strategies directed toward this gene product
      are likely to confer a therapeutic benefit for antiviral drugs or the development
      of a SARS vaccine.

PMID- 15140962
TI  - Increased sensitivity to CD4 binding site-directed neutralization following in
      vitro propagation on primary lymphocytes of a neutralization-resistant human
      immunodeficiency virus IIIB strain isolated from an accidentally infected
      laboratory worker.
AB  - We previously described the adaptation of the neutralization-sensitive human
      immunodeficiency virus type 1 (HIV-1) strain IIIB to a neutralization-resistant
      phenotype in an accidentally infected laboratory worker. During long-term
      propagation of this resistant isolate, designated FF3346, on primary peripheral
      blood leukocytes in vitro, an HIV-1 variant appeared that had regained
      sensitivity to neutralization by soluble CD4 (sCD4) and the broadly neutralizing
      monoclonal antibody b12. When an early passage of FF3346 was subjected to
      limiting-dilution culture in peripheral blood mononuclear cells, eight virus
      variants with various degrees of neutralization resistance were isolated. Two of
      them, the sCD4 neutralization-resistant variant LW_H8(res) and the sCD4
      neutralization-sensitive variant LW_G9(sens), were selected for further study.
      Interestingly, these two viruses were equally resistant to neutralization by
      agents that recognize domains other than the CD4 binding site. Site-directed
      mutagenesis revealed that the increased neutralization sensitivity of variant
      LW_G9(sens) resulted from only two changes, an Asn-to-Ser substitution at
      position 164 in the V2 loop and an Ala-to-Glu substitution at position 370 in the
      C3 domain of gp120. In agreement with this notion, the affinity of b12 for
      monomeric gp120 containing the N164S and A370E substitutions in the background of
      the molecular clone LW_H8(res) was higher than its affinity for the parental
      gp120. Surprisingly, no correlation was observed between CD4 binding affinity for
      monomeric gp120 and the level of neutralization resistance, suggesting that
      differences in sCD4 neutralization sensitivity between these viruses are only
      manifested in the context of the tertiary or quaternary structure of gp120 on the
      viral surface. The results obtained here indicate that the neutralization
      sensitive strain IIIB can become neutralization resistant in vivo under selective
      pressure by neutralizing antibodies but that this resistance may be easily
      reversed in the absence of immunological pressure.

PMID- 15140965
TI  - A bunyamwera virus minireplicon system in mosquito cells.
AB  - Artificial minigenomes are powerful tools for studying the replication and
      transcription of negative-strand RNA viruses. Bunyamwera virus (BUN; genus
      Orthobunyavirus, family Bunyaviridae) is an arbovirus that shows fundamental
      biological differences when replicating in mammalian versus mosquito cells. To
      study BUN RNA synthesis in mosquito cells, we developed a bacteriophage T7 RNA
      polymerase-based minireplicon system similar to that described previously for
      mammalian cells. An Aedes albopictus C6/36-derived mosquito cell line stably
      expressing T7 RNA polymerase was established. Viral proteins and artificial
      minigenomes (containing Renilla luciferase as a reporter) were transcribed and
      expressed in these cells from transfected T7 promoter-containing plasmids.
      Transcription of the minigenome required two viral proteins, the nucleocapsid
      protein N and the RNA-dependent RNA polymerase L, a situation similar to that in
      mammalian cells. However, unlike the situation in mammalian cells, the viral
      polymerase was not inhibited by the viral nonstructural protein NSs. We also
      report that promoter strength is different for vertebrate versus invertebrate
      cells. The development of this system opens the way for a detailed comparison of
      bunyavirus replication in cells of disparate phylogeny.

PMID- 15140963
TI  - Murine coronavirus replication induces cell cycle arrest in G0/G1 phase.
AB  - Mouse hepatitis virus (MHV) replication in actively growing DBT and 17Cl-1 cells
      resulted in the inhibition of host cellular DNA synthesis and the accumulation of
      infected cells in the G(0)/G(1) phase of the cell cycle. UV-irradiated MHV failed
      to inhibit host cellular DNA synthesis. MHV infection in quiescent 17Cl-1 cells
      that had been synchronized in the G(0) phase by serum deprivation prevented
      infected cells from entering the S phase after serum stimulation. MHV replication
      inhibited hyperphosphorylation of the retinoblastoma protein (pRb), the event
      that is necessary for cell cycle progression through late G(1) and into the S
      phase. While the amounts of the cellular cyclin-dependent kinase (Cdk) inhibitors
      p21(Cip1), p27(Kip1), and p16(INK4a) did not change in infected cells, MHV
      infection in asynchronous cultures induced a clear reduction in the amounts of
      Cdk4 and G(1) cyclins (cyclins D1, D2, D3, and E) in both DBT and 17Cl-1 cells
      and a reduction in Cdk6 levels in 17Cl-1 cells. Infection also resulted in a
      decrease in Cdk2 activity in both cell lines. MHV infection in quiescent 17Cl-1
      cells prevented normal increases in Cdk4, Cdk6, cyclin D1, and cyclin D3 levels
      after serum stimulation. The amounts of cyclin D2 and cyclin E were not increased
      significantly after serum stimulation in mock-infected cells, whereas they were
      decreased in MHV-infected cells, suggesting the possibility that MHV infection
      may induce cyclin D2 and cyclin E degradation. Our data suggested that a
      reduction in the amounts of G(1) cyclin-Cdk complexes in MHV-infected cells led
      to a reduction in Cdk activities and insufficient hyperphosphorylation of pRb,
      resulting in inhibition of the cell cycle in the G(0)/G(1) phase.

PMID- 15140964
TI  - Capsid is a dominant determinant of retrovirus infectivity in nondividing cells.
AB  - A major difference between lentiviruses such as human immunodeficiency virus
      (HIV) and most other retroviruses is their ability to productively infect
      nondividing cells. We present here genetic evidence for involvement of the capsid
      protein (CA) in the infectious phenotype in nondividing cells. A chimeric HIV
      type 1 (HIV-1) in which the MA and CA of HIV-1 are replaced with the MA, p12, and
      CA encoding sequences from murine leukemia virus (MLV) loses the ability to
      efficiently infect nondividing cells. Analysis of the accumulation of two-long
      terminal-repeat circles implies that the impairment of nuclear transport of
      preintegration complexes is responsible for the restricted infection of this
      chimeric virus in nondividing cells. Incorporation of MLV MA and MLV p12 into HIV
      virions alone does not exert any adverse effects on viral infection in interphase
      cells. These results suggest that CA is the dominant determinant for the
      difference between HIV and MLV in the ability to transduce nondividing cells.

PMID- 15140966
TI  - Passive and active inclusion of host proteins in human immunodeficiency virus
      type 1 gag particles during budding at the plasma membrane.
AB  - Human immunodeficiency virus type 1 particles form by budding at the surface of
      most cell types. In this process, a piece of the plasma membrane is modified into
      an enveloped virus particle. The process is driven by the internal viral protein
      Pr55(gag). We have studied how host proteins in the membrane are dealt with by
      Pr55(gag) during budding. Are they included in or excluded from the particle? The
      question was approached by measuring the relative concentrations of host and
      viral proteins in the envelope of Pr55(gag) particles and in their donor
      membranes in the cell. We observed that the bulk of the host proteins, including
      actin and clathrin, were passively included into the virus-like Gag particles.
      This result suggests that budding by Pr55(gag) proceeds without significant
      alteration of the original host protein composition at the cell membrane.
      Nevertheless, some proteins were concentrated in the particles, and a few were
      excluded. The concentrated proteins included cyclophilin A and Tsg-101. These
      were recruited to the plasma membrane by Pr55(gag). The membrane-bound
      cyclophilin A was concentrated into particles as efficiently as Pr55(gag),
      whereas Tsg-101 was concentrated more efficiently. The latter finding is
      consistent with a role for Tsg-101 in Gag particle release.

PMID- 15140967
TI  - Degradation of p53, not telomerase activation, by E6 is required for bypass of
      crisis and immortalization by human papillomavirus type 16 E6/E7.
AB  - Bypass of two arrest points is essential in the process of cellular
      immortalization, one of the components of the transformation process. Expression
      of human papillomavirus type 16 E6 and E7 together can escape both senescence and
      crisis, processes which normally limit the proliferative capacity of primary
      human keratinocytes. Crisis is thought to be mediated by telomere shortening.
      Because E6 stimulates telomerase activity and exogenous expression of the TERT
      gene with E7 can immortalize keratinocytes, this function is thought to be
      important for E6 to cooperate with E7 to bypass crisis. However, it has also been
      reported that E6 dissociates increased telomerase activity from maintenance of
      telomere length and that a dominant-negative p53 molecule can substitute for E6
      in cooperative immortalization of keratinocytes with E7. Thus, to determine which
      functions of E6 are required to allow bypass of crisis and immortalization of
      keratinocytes with E7, immortalization assays were performed using specific
      mutants of E6, in tandem with E7. In these experiments, every clone expressing an
      E6 mutant capable of degrading p53 was able to bypass crisis and immortalize,
      regardless of telomerase induction. All clones containing E6 mutants incapable of
      degrading p53 died at crisis. These results suggest that the ability of E6 to
      induce degradation of p53 compensates for continued telomere shortening in E6/E7
      cells and demonstrate that degradation of p53 is required for immortalization by
      E6/E7, while increased telomerase activity is dispensable.

PMID- 15140968
TI  - Longitudinal analysis of CD8+ T cells specific for structural and nonstructural
      hepatitis B virus proteins in patients with chronic hepatitis B: implications for
      immunotherapy.
AB  - The cytotoxic T-cell response in chronic hepatitis B virus (HBV) infection has
      been described as weak and mono- or oligospecific in comparison to the more
      robust virus-specific T-cell response present in resolved infection. However,
      chronic hepatitis B is a heterogeneous disease with markedly variable levels of
      virus replication and liver disease activity. Here we analyzed (both directly ex
      vivo and after in vitro stimulation) the HBV-specific CD8 T-cell responses
      against structural and nonstructural HBV proteins longitudinally in patients with
      different patterns of chronic infections. We found that the profiles of virus
      specific CD8(+)-T-cell responses during chronic infections are highly
      heterogeneous and influenced more by the level of HBV replication than by the
      activity of liver disease. An HBV DNA load of <10(7) copies/ml appears to be the
      threshold below which circulating multispecific HBV-specific CD8(+) T cells are
      consistently detected. Furthermore, CD8(+) T cells with different specificities
      are differentially regulated during chronic infections. HBV core-specific CD8(+)
      T cells are associated with viral control, while CD8(+) T cells specific for
      envelope and polymerase epitopes can occasionally be found in the setting of high
      levels (>10(7) copies) of HBV replication. These findings have implications for
      the design of immunotherapy for chronic HBV infections.

PMID- 15140969
TI  - IGFBP-3, a marker of cellular senescence, is overexpressed in human
      papillomavirus-immortalized cervical cells and enhances IGF-1-induced
      mitogenesis.
AB  - Human ectocervical cells, following retroviral transduction with the human
      papillomavirus type 16 E6/E7 oncogenes, are altered in their array of transcribed
      cellular genes, including increased mRNA for the insulin-like growth factor
      binding protein 3 (IGFBP-3). IGFBP-3 expression is associated with cellular
      senescence, and its addition to many cell types inhibits growth or induces
      apoptosis. By immunoblotting and enzyme-linked immunosorbent assay methods, we
      demonstrate that late-passage, immortalized E6/E7-transduced cells secrete high
      levels of IGFBP-3 (25 ng/ml), which represent a 500-fold increase compared to
      levels in early-passage, nonimmortalized transduced cells (<0.05 ng/ml).
      Concomitantly, these late-passage cervical cells exhibit an increase in
      sensitivity to IGF-1, including enhanced phosphorylation of the IGF receptor (IGF
      R) and insulin receptor substrate as well as increased DNA synthesis (5-fold) and
      cell proliferation (3.7-fold). However, there was no change in the level of IGF-R
      in these cells (surface or total), and the cells did not synthesize IGF-1,
      indicating that these arms of the IGF pathway were independently regulated and
      not responsible for the augmented signaling. Consistent with a causal
      relationship between IGFBP-3 expression and enhanced IGF-1 responses, we found
      that early-passage cells could be converted to the late-passage, IGF-1-responsive
      phenotype by preincubation with IGFBP-3. Thus, in contrast to findings with some
      cell types, IGFBP-3 expression in cervical cells is associated with augmented IGF
      1 signaling and cell proliferation and correlates with the timing of cellular
      immortalization.

PMID- 15140970
TI  - Styrylquinolines, integrase inhibitors acting prior to integration: a new
      mechanism of action for anti-integrase agents.
AB  - We have previously shown that styrylquinolines (SQLs) are integrase inhibitors in
      vitro. They compete with the long terminal repeat substrate for integrase. Here,
      we describe the cellular mode of action of these molecules. We show that SQLs do
      not interfere with virus entry. In fact, concentrations of up to 20 times the 50%
      inhibitory concentration did not inhibit cell-to-cell fusion or affect the
      interaction between GP120 and CD4 in vitro. Moreover, the pseudotype of the
      retrovirus envelope did not affect drug activity. Quantitative reverse
      transcription PCR experiments showed that SQLs do not inhibit the entry of the
      genomic RNA. In contrast, the treatment of human immunodeficiency virus type 1
      infected cells with SQLs reduced the amount of the late cDNA, suggesting for the
      first time that integrase targeting molecules may affect the accumulation of DNA
      during reverse transcription. The cellular target of SQLs was confirmed by the
      appearance of mutations in the integrase gene when viruses were grown in the
      presence of increasing concentrations of SQLs. Finally, these mutations led to
      SQL-resistant viruses when introduced into the wild-type sequence. In contrast,
      SQLs were fully active against reverse transcriptase inhibitor- and diketo acid
      resistant viruses, positioning SQLs as a second group of anti-integrase
      compounds.

PMID- 15140971
TI  - Features affecting the ability of hepatitis delta virus RNAs to initiate RNA
      directed RNA synthesis.
AB  - In models of the replication of human hepatitis delta virus (HDV) RNA, it is
      generally assumed that circular RNAs are the only templates. However, noncircular
      HDV RNAs are also produced during replication, and it is known that replication
      can be initiated by transfection with noncircular RNAs. Therefore, strategies
      were devised to determine the relative ability of different HDV RNA species to
      initiate RNA replication. One strategy used in vivo intermolecular competition
      following cotransfection into cells, between two sequence-marked HDV RNA species.
      Circular RNA templates were found to be at least severalfold more efficient than
      a dimeric linear template. Unit-length linear species, that is, equivalent to
      circles opened at different sites, were in most cases but not always of
      efficiency comparable to that of each other. Greater-than-unit-length linear
      species were more efficient than unit-length species, presumably because of the
      increased opportunities for template switching. Genomic linear RNAs were
      generally of initiation ability comparable to that of antigenomic RNAs. A second
      strategy measured the ability of initiation to occur on different regions of HDV
      RNAs that were twice the unit length. In summary, results from these two
      experimental strategies make clear that linear HDV RNA species, as well as
      circles, can contribute to the overall process of HDV genome replication. In
      addition, the results from the two experimental strategies provided information
      on the impact of template switching during RNA-directed transcription.

PMID- 15140972
TI  - Disruption of the actin cytoskeleton can complement the ability of Nef to enhance
      human immunodeficiency virus type 1 infectivity.
AB  - The human immunodeficiency virus (HIV) protein Nef has been shown to increase the
      infectivity of HIV at an early point during infection. Since Nef is known to
      interact with proteins involved in actin cytoskeleton rearrangements, we tested
      the possibility that Nef may enhance HIV infectivity via a mechanism that
      involves the actin cytoskeleton. We find that disruption of the actin
      cytoskeleton complements the Nef infectivity defect. The ability of disruption of
      the actin cytoskeleton to complement the Nef defect was specific to envelopes
      that fuse at the cell surface, including a variety of HIV envelopes and the
      murine leukemia virus amphotropic envelope. In contrast, the infectivity of HIV
      virions pseudotyped to enter cells via endocytosis, which is known to complement
      the HIV Nef infectivity defect and can naturally penetrate the cortical actin
      barrier, was not altered by actin cytoskeleton disruption. The results presented
      here suggest that Nef functions to allow the HIV genome to penetrate the cortical
      actin network, a known barrier for intracellular parasitic organisms.

PMID- 15140973
TI  - The dominant-negative herpes simplex virus type 1 (HSV-1) recombinant CJ83193 can
      serve as an effective vaccine against wild-type HSV-1 infection in mice.
AB  - By selectively regulating the expression of the trans-dominant-negative mutant
      polypeptide UL9-C535C, of herpes simplex virus type 1 (HSV-1) origin binding
      protein UL9 with the tetracycline repressor (tetR)-mediated gene switch, we
      recently generated a novel replication-defective and anti-HSV-specific HSV-1
      recombinant, CJ83193. The UL9-C535C peptides expressed by CJ83193 can function as
      a potent intracellular therapy against its own replication, as well as the
      replication of wild-type HSV-1 and HSV-2 in coinfected cells. In this report, we
      demonstrate that CJ83193 cannot initiate acute productive infection in corneas of
      infected mice nor can it reactivate from trigeminal ganglia of mice latently
      infected by CJ83193 in a mouse ocular model. Given that CJ83193 is capable of
      expressing the viral alpha, beta, and gamma1 genes but little or no gamma2 genes,
      we tested the vaccine potential of CJ83193 against HSV-1 infection in a mouse
      ocular model. Our studies showed that immunization with CJ83193 significantly
      reduced the yields of challenge HSV in the eyes and trigeminal ganglia on days 3,
      5, and 7 postchallenge. Like in mice immunized with the wild-type HSV-1 strain
      KOS, immunization of mice with CJ83193 prevents the development of keratitis and
      encephalitis induced by corneal challenge with wild-type HSV-1 strain mP. Delayed
      type hypersensitivity (DTH) assays demonstrate that CJ83193 can elicit durable
      cell-mediated immunity at the same level as that of wild-type HSV-1 and is more
      effective than that induced by d27, an HSV-1 ICP27 deletion mutant. Moreover,
      mice immunized with CJ83193 developed strong, durable HSV-1-neutralizing
      antibodies at levels at least twofold higher than those induced by d27. The
      results presented in this report have shed new light on the development of
      effective HSV viral vaccines that encode a unique safety mechanism capable of
      inhibiting the mutant's own replication and that of wild-type virus.

PMID- 15140974
TI  - Complementation of a binding-defective retrovirus by a host cell receptor mutant.
AB  - The entry of ecotropic murine leukemia virus (MLV) into cells requires the
      interaction of the envelope protein (Env) with its receptor, mouse cationic amino
      acid transporter 1 (mATRC1). An aspartic acid-to-lysine change at position 84
      (D84K) of ecotropic Moloney MLV Env abolishes virus binding and infection. We
      recently identified lysine 234 (rK234) in mATRC1 as a residue that influences
      virus binding and infection. Here we show that D84K virus infection increased
      3,000-fold on cells expressing receptor with an rK234A change and 100,000-fold on
      cells expressing an rK234D change. The stronger complementation of D84K virus
      infection by rK234D than by the rK234A receptor suggests that although the major
      reason for loss of infection of D84K and D84R virus is due to steric hindrance
      and charge repulsion, the loss of an interaction of D84 with receptor appears to
      contribute as well. Taken together, these results indicate that D84 is very close
      to rK234 of mATRC1 in the bound complex and there is likely an interaction
      between them. The definitive localization of the receptor binding site on SU
      should facilitate the design of chimeric envelope proteins that target infection
      to new receptors by replacing the receptor binding site with an exogenous ligand
      sequence.

PMID- 15140975
TI  - Recombinant respiratory syncytial viruses lacking the C-terminal third of the
      attachment (G) protein are immunogenic and attenuated in vivo and in vitro.
AB  - The design of attenuated vaccines for respiratory syncytial virus (RSV)
      historically focused on viruses made sensitive to physiologic temperature through
      point mutations in the genome. These prototype vaccines were not suitable for
      human infants primarily because of insufficient attenuation, genetic instability,
      and reversion to a less-attenuated phenotype. We therefore sought to construct
      novel attenuated viruses with less potential for reversion through genetic
      alteration of the attachment G protein. Complete deletion of G protein was
      previously shown to result in RSV strains overly attenuated for replication in
      mice. Using reverse genetics, recombinant RSV (rRSV) strains were engineered with
      truncations at amino acid 118, 174, 193, or 213 and respectively designated
      rA2cpDeltaG118, rA2cpDeltaG174, rA2cpDeltaG193, and rA2cpDeltaG213. All
      rA2cpDeltaG strains were attenuated for growth in vitro and in the respiratory
      tracts of BALB/c mice but not restricted for growth at 37 degrees C. The
      mutations did not significantly affect nascent genome synthesis in human lung
      epithelial (A549) cells, but infectious rA2cpDeltaG virus shed into the culture
      medium was dramatically diminished. Hence, the data suggested that a site within
      the C-terminal 85 amino acids of G protein is important for efficient genome
      packaging or budding of RSV from the infected cell. Vaccination with the
      rA2cpDeltaG strains also generated efficacious immune responses in mice that were
      similar to those elicited by the temperature-sensitive cpts248/404 strain
      previously tested in human infants. Collectively, the data indicate that the
      rA2cpDeltaG strains are immunogenic, not likely to revert to the less-attenuated
      phenotype, and thus candidates for further development as vaccines against RSV.

PMID- 15140976
TI  - Multiple groups of endogenous betaretroviruses in mice, rats, and other mammals.
AB  - Betaretroviruses exist in endogenous and exogenous forms in hosts that are widely
      distributed and evolutionarily distantly related. Here we report the discovery
      and characterization of several previously unknown betaretrovirus groups in the
      genomes of Mus musculus and Rattus norvegicus. Each group contains both mouse and
      rat elements, and several of the groups are more closely related to previously
      known betaretroviruses from nonmurine hosts. Some of the groups also include
      members from hosts which were not previously known to harbor betaretroviruses,
      such as the gray mouse lemur (Microcebus murinus) and Seba's short-tailed bat
      (Carollia perspicillata). Some of the mouse and rat elements possess intact open
      reading frames for gag, pro, pol, and/or env genes and display characteristics of
      having retrotransposed recently. We propose a model whereby betaretroviruses have
      been evolving within the genomes of murid rodents for at least the last 20
      million years and, subsequent to (or concomitant with) the global spread of their
      murid hosts, have occasionally been transmitted to other species.

PMID- 15140977
TI  - Density-dependent selection in vesicular stomatitis virus.
AB  - We used vesicular stomatitis virus to test the effect of complementation on the
      relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant
      (MARM) N, in competition with its wild-type ancestor. We carried out competitions
      of MARM N and wild-type populations at different multiplicities of infection
      (MOIs) and initial ratios of the wild type to the mutant and found that the
      fitness of MARM N relative to that of the wild type is very sensitive to changes
      in the MOI (i.e., the degree of complementation) but depends little, if at all,
      on the initial frequencies of MARM N and the wild type. Further, we developed a
      mathematical model under the assumption that during coinfection both viruses
      contribute to a common pool of protein products in the infected cell and that
      they both exploit this common pool equally. Under such conditions, the fitness of
      all virions that coinfect a cell is the average fitness in the absence of
      coinfection of that group of virions. In the absence of coinfection,
      complementation cannot take place and the relative fitness of each competitor is
      only determined by the selective value of its own products. We found good
      agreement between our experimental results and the model predictions, which
      suggests that the wild type and MARM N freely share all of their gene products
      under coinfection.

PMID- 15140978
TI  - Porcine endogenous retrovirus transmission characteristics of galactose alpha1-3
      galactose-deficient pig cells.
AB  - Galactose alpha1-3 galactose (Gal) trisaccharides are present on the surface of
      wild-type pig cells, as well as on viruses particles produced from such cells.
      The recognition of Gal sugars by natural anti-Gal antibodies (NAb) in human and
      Old World primate serum can cause the lysis of the particles via complement
      dependent mechanisms and has therefore been proposed as an important antiviral
      mechanism. Recently, pigs have been generated that possess disrupted galactosyl
      transferase (GGTA1) genes. The cells of these pigs do not express Gal sugars on
      their surface, i.e., are Gal null. Concerns have been raised that the risk of
      virus transmission from such pigs may be increased due to the absence of the Gal
      sugars. We investigated the sensitivity of porcine endogenous retrovirus (PERV)
      produced from Gal-null and Gal-positive pig cells to inactivation by purified NAb
      and human serum. PERV produced in Gal-null pig cells was resistant to
      inactivation by either NAb or human serum. In contrast, although Gal-positive
      PERV particles were sensitive to inactivation by NAb and human serum, they
      required markedly higher concentrations of NAb for inactivation compared to the
      Gal-positive cells from which they were produced. Complete inactivation of Gal
      positive PERV particles was not achievable despite the use of high levels of NAb,
      indicating that NAb-mediated inactivation of cell-free PERV particles is an
      inefficient process.

PMID- 15140979
TI  - Reduced sensitivity to human serum inactivation of enveloped viruses produced by
      pig cells transgenic for human CD55 or deficient for the galactosyl-alpha(1-3)
      galactosyl epitope.
AB  - Complement activation mediated by the major xenogeneic epitope in the pig,
      galactosyl-alpha(1-3) galactosyl sugar structure (alpha-Gal), and human natural
      antibodies could cause hyperacute rejection (HAR) in pig-to-human
      xenotransplantation. The same reaction on viruses bearing alpha-Gal may serve as
      a barrier to zoonotic infection. Expressing human complement regulatory proteins
      or knocking out alpha-Gal epitopes in pig in order to overcome HAR may therefore
      pose an increased risk in xenotransplantation with regard to zoonosis. We
      investigated whether amphotropic murine leukemia virus, porcine endogenous
      retrovirus, and vesicular stomatitis virus (VSV) budding from primary transgenic
      pig aortic endothelial (TgPAE) cells expressing human CD55 (hCD55 or hDAF) was
      protected from human-complement-mediated inactivation. VSV propagated through the
      ST-IOWA pig cell line, in which alpha-galactosyl-transferase genes were disrupted
      (Gal null), was also tested for sensitivity to human complement. The TgPAE cells
      were positive for hCD55, and all pig cells except the Gal-null ST-IOWA expressed
      alpha-Gal epitopes. Through antibody binding, we were able to demonstrate the
      incorporation of hCD55 onto VSV particles. Viruses harvested from TgPAE cells
      were relatively resistant to complement-mediated inactivation by the three
      sources of human sera tested. Additionally, VSV from Gal-null pig cells was
      resistant to human complement inactivation. Such protection of enveloped viruses
      may increase the risk of zoonosis from pigs genetically modified for pig-to-human
      xenotransplantation.

PMID- 15140980
TI  - Microarray analysis reveals characteristic changes of host cell gene expression
      in response to attenuated modified vaccinia virus Ankara infection of human HeLa
      cells.
AB  - The potential use of the modified vaccinia virus Ankara (MVA) strain as a live
      recombinant vector to deliver antigens and elicit protective immune responses
      against infectious diseases demands a comprehensive understanding of the effect
      of MVA infection on human host gene expression. We used microarrays containing
      more than 15,000 human cDNAs to identify gene expression changes in human HeLa
      cell cultures at 2, 6, and 16 h postinfection. Clustering of the 410
      differentially regulated genes identified 11 discrete gene clusters with altered
      expression patterns after MVA infection. Clusters 1 and 2 (accounting for 16.59%
      [68 of 410] of the genes) contained 68 transcripts showing a robust induction
      pattern that was maintained during the course of infection. Changes in cellular
      gene transcription detected by microarrays after MVA infection were confirmed for
      selected genes by Northern blot analysis and by real-time reverse transcription
      PCR. Upregulated transcripts in clusters 1 and 2 included 20 genes implicated in
      immune responses, including interleukin 1A (IL-1A), IL-6, IL-7, IL-8, and IL-15
      genes. MVA infection also stimulated the expression of NF-kappaB and components
      of the NF-kappaB signal transduction pathway, including p50 and TRAF-interacting
      protein. A marked increase in the expression of histone family members was also
      induced during MVA infection. Expression of the Wiskott-Aldrich syndrome family
      members WAS, WASF1, and the small GTP-binding protein RAC-1, which are involved
      in actin cytoskeleton reorganization, was enhanced after MVA infection. This
      study demonstrates that MVA infection triggered the induction of groups of genes,
      some of which may be involved in host resistance and immune modulation during
      virus infection.

PMID- 15140981
TI  - Human immunodeficiency virus type 1 (HIV-1) integrase: resistance to diketo acid
      integrase inhibitors impairs HIV-1 replication and integration and confers cross
      resistance to L-chicoric acid.
AB  - The diketo acids are potent inhibitors of human immunodeficiency virus (HIV)
      integrase (IN). Mutations in IN, T66I, S153Y, and M154I, as well as T66I-S153Y
      and T66I-M154I double mutations, confer resistance to diketo acids (D. J. Hazuda
      et al., Science 287:646-650, 2000). The effects of these IN mutations on viral
      replication, enzymatic activity, and susceptibility to other HIV inhibitors are
      reported herein. By immunofluorescence assay and real-time PCR, all mutant
      viruses demonstrated a modest delay in viral spread compared to that of reference
      HIV. These viruses also showed a statistically significant defect in integration
      without defects in reverse transcription. Recombinant IN containing S153Y, T66I,
      and M154I-T66I mutations had an approximately twofold decrease in both
      disintegration and 3'-end-processing-strand transfer activities in vitro. In
      contrast, IN containing M154I demonstrated a greater than twofold increase in
      specific activity in both reactions. All mutant HIVs were resistant to l-chicoric
      acid, a dicaffeoyltartaric acid IN inhibitor, both in tissue culture and in
      biochemical assays, yet remained susceptible to the reverse transcriptase
      inhibitors zidovudine and nevirapine. Thus, IN mutations conferring resistance to
      the diketo acids can yield integration defects, attenuated catalysis in vitro,
      and cross-resistance to l-chicoric acid.

PMID- 15140982
TI  - Integrase-specific enhancement and suppression of retroviral DNA integration by
      compacted chromatin structure in vitro.
AB  - Integration of viral DNA into the host chromosome is an obligatory step in
      retroviral replication and is dependent on the activity of the viral enzyme
      integrase. To examine the influence of chromatin structure on retroviral DNA
      integration in vitro, we used a model target comprising a 13-nucleosome extended
      array that includes binding sites for specific transcription factors and can be
      compacted into a higher-ordered structure. We found that the efficiency of in
      vitro integration catalyzed by human immunodeficiency virus type 1 (HIV-1)
      integrase was decreased after compaction of this target with histone H1. In
      contrast, integration by avian sarcoma virus (ASV) integrase was more efficient
      after compaction by either histone H1 or a high salt concentration, suggesting
      that the compacted structure enhances this reaction. Furthermore, although site
      specific binding of transcription factors HNF3 and GATA4 blocked ASV DNA
      integration in extended nucleosome arrays, local opening of H1-compacted
      chromatin by HNF3 had no detectable effect on integration, underscoring the
      preference of ASV for compacted chromatin. Our results indicate that chromatin
      structure affects integration site selection of the HIV-1 and ASV integrases in
      opposite ways. These distinct properties of integrases may also affect target
      site selection in vivo, resulting in an important bias against or in favor of
      integration into actively transcribed host DNA.

PMID- 15140984
TI  - Hepatitis C virus persistence after spontaneous or treatment-induced resolution
      of hepatitis C.
AB  - It is presumed that resolution of hepatitis C, as evidenced by normalization of
      liver function tests and disappearance of hepatitis C virus (HCV) RNA from serum,
      as determined by conventional laboratory assays, reflects virus eradication. In
      this study, we examined the expression of the HCV genome in the sera, peripheral
      blood mononuclear cells (PBMC), and, on some occasions, monocyte-derived
      dendritic cells (DC) long after resolution of hepatitis C by using a highly
      sensitive reverse transcription (RT)-PCR-nucleic acid hybridization (RT-PCR-NAH)
      assay. The samples obtained from 16 randomly selected patients (5 with
      spontaneous and 11 with treatment-induced resolution), monitored for up to 5
      years, were studied by qualitative and semiquantitative RT-PCR-NAH and by real
      time RT-PCR to detect the HCV RNA positive strand. The replicative HCV RNA
      negative strand was examined in PBMC after culture with a T-cell proliferation
      stimulating mitogen. The findings show that HCV RNA was carried in the
      convalescent-phase sera and/or PBMC in all 16 individuals investigated. Also, DC
      from six of seven patients were reactive for the HCV genome. Importantly, traces
      of the HCV RNA negative strand, suggesting progressing virus replication, were
      detected in the majority of mitogen-stimulated PBMC, including four samples
      collected 5 years after recovery. Sequencing of the HCV 5' untranslated region
      fragment revealed genotype 1b in four of nine individuals examined and genotypes
      1a and 2a in three and two patients, respectively. These results imply that HCV
      RNA can persist at very low levels in the serum and peripheral lymphoid cells and
      that an intermediate replicative form of the HCV genome can persist in PBMC for
      many years after apparently complete spontaneous or antiviral therapy-induced
      resolution of chronic hepatitis C.

PMID- 15140985
TI  - The NV gene of snakehead rhabdovirus (SHRV) is not required for pathogenesis, and
      a heterologous glycoprotein can be incorporated into the SHRV envelope.
AB  - Snakehead rhabdovirus (SHRV) affects warm-water fish in Southeast Asia and
      belongs to the genus Novirhabdovirus by virtue of its "nonvirion" (NV) gene. To
      examine the function of the NV gene, we used a recently developed reverse genetic
      system to produce a viable recombinant SHRV carrying an NV gene deletion. The
      recombinant virus was produced at the same rate and same final concentrations as
      the wild-type virus in cultured fish cells in spite of the NV gene deletion. The
      role of the NV protein in fish pathogenesis was also investigated. Zebra fish
      (Danio rerio) were infected with the NV deletion mutant or with a recombinant
      virus containing a copy of the SHRV genome, and similar mortality rates as well
      as final mortalities were recorded, suggesting no apparent role for the NV
      protein in fish pathogenesis. Interestingly, the unsuccessful rescue of fully
      viable recombinants with genomes containing deletions in the G/NV gene junction
      suggested a role for the gene junction in virus transcription and replication.
      Finally, we demonstrated that the SHRV glycoprotein can be replaced by the
      glycoprotein of infectious hematopoietic necrosis virus (IHNV) or by a hybrid
      protein composed of SHRV and IHNV sequences.

PMID- 15140983
TI  - Proteomics of herpes simplex virus replication compartments: association of
      cellular DNA replication, repair, recombination, and chromatin remodeling
      proteins with ICP8.
AB  - In this study, we have used immunoprecipitation and mass spectrometry to identify
      over 50 cellular and viral proteins that are associated with the herpes simplex
      virus 1 (HSV-1) ICP8 single-stranded DNA-binding protein. Many of the
      coprecipitating cellular proteins are known members of large cellular complexes
      involved in (i) DNA replication or damage repair, including RPA and MSH6; (ii)
      nonhomologous and homologous recombination, including the catalytic subunit of
      the DNA-dependent protein kinase, Ku86, and Rad50; and (iii) chromatin
      remodeling, including BRG1, BRM, hSNF2H, BAF155, mSin3a, and histone deacetylase
      2. It appears that DNA mediates the association of certain proteins with ICP8,
      while more direct protein-protein interactions mediate the association with other
      proteins. A number of these proteins accumulate in viral replication compartments
      in the infected cell nucleus, indicating that these proteins may have a role in
      viral replication. WRN, which functions in cellular recombination pathways via
      its helicase and exonuclease activities, is not absolutely required for viral
      replication, as viral yields are only very slightly, if at all, decreased in WRN
      deficient human primary fibroblasts compared to control cells. In Ku70-deficient
      murine embryonic fibroblasts, viral yields are increased by almost 50-fold,
      suggesting that the cellular nonhomologous end-joining pathway inhibits HSV
      replication. We hypothesize that some of the proteins coprecipitating with ICP8
      are involved in HSV replication and may give new insight into viral replication
      mechanisms.

PMID- 15140986
TI  - Suppression of proinflammatory cytokine expression by herpes simplex virus type
      1.
AB  - Viral immune evasion strategies are important for establishment and maintenance
      of infections. Many viruses are in possession of mechanisms to counteract the
      antiviral response raised by the infected host. Here we show that a herpes
      simplex virus type 1 (HSV-1) mutant lacking functional viral protein 16 (VP16)-a
      tegument protein promoting viral gene expression-induced significantly higher
      levels of proinflammatory cytokines than wild-type HSV-1. This was observed in
      several cell lines and primary murine macrophages, as well as in peritoneal cells
      harvested from mice infected in vivo. The enhanced ability to stimulate cytokine
      expression in the absence of VP16 was not mediated directly by VP16 but was
      dependent on the viral immediate-early genes for infected cell protein 4 (ICP4)
      and ICP27, which are expressed in a VP16-dependent manner during primary HSV
      infection. The virus appeared to target cellular factors other than interferon
      induced double-stranded RNA-activated protein kinase R (PKR), since the virus
      mutants remained stronger inducers of cytokines in cells stably expressing a
      dominant-negative mutant form of PKR. Finally, mRNA stability assay revealed a
      significantly longer half-life for interleukin-6 mRNA after infection with the
      VP16 mutant than after infection with the wild-type virus. Thus, HSV is able to
      suppress expression of proinflammatory cytokines by decreasing the stability of
      mRNAs, thereby potentially impeding the antiviral host response to infection.

PMID- 15140987
TI  - Antisense morpholino-oligomers directed against the 5' end of the genome inhibit
      coronavirus proliferation and growth.
AB  - Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat
      represents a novel method for delivery of antisense morpholino-oligomers.
      Conjugated and unconjugated oligomers were tested to determine sequence-specific
      antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus
      (MHV). Specific antisense activity designed to block translation of the viral
      replicase polyprotein was first confirmed by reduction of luciferase expression
      from a target sequence-containing reporter construct in both cell-free and
      transfected cell culture assays. Peptide-conjugated morpholino-oligomers
      exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer
      administered at micromolar concentrations was delivered to >80% of cells and
      inhibited virus titers 10- to 100-fold in a sequence-specific and dose-responsive
      manner. In addition, targeted viral protein synthesis, plaque diameter, and
      cytopathic effect were significantly reduced. Inhibition of virus infectivity by
      peptide-conjugated morpholino was comparable to the antiviral activity of the
      aminoglycoside hygromycin B used at a concentration fivefold higher than the
      oligomer. These results suggest that this composition of antisense compound has
      therapeutic potential for control of coronavirus infection.

PMID- 15140988
TI  - Processing of a pestivirus protein by a cellular protease specific for light
      chain 3 of microtubule-associated proteins.
AB  - The genome of the cytopathogenic (cp) bovine viral diarrhea virus (BVDV) JaCP
      contains a cellular insertion coding for light chain 3 (LC3) of microtubule
      associated proteins, the mammalian homologue of yeast Aut7p/Apg8p. The cellular
      insertion induces cp BVDV-specific processing of the viral polyprotein by a
      cellular cysteine protease homologous to the known yeast protease Aut2p/Apg4p.
      Three candidate bovine protease genes were identified on the basis of the
      sequence similarity of their products with the Saccharomyces cerevisiae enzyme.
      The search for a system for functional testing of these putative LC3-specific
      proteases revealed that the components involved in this processing have been
      highly conserved during evolution, so that the substrate derived from a mammalian
      virus is processed in cells of mammalian, avian, fish, and insect origin, as well
      as in rabbit reticulocyte lysate, but not in wheat germ extracts. Moreover, two
      of these proteases and a homologous protein from chickens were able to rescue the
      defect of a yeast AUT2 deletion mutant. In coexpression experiments with yeast
      and wheat germ extracts one of the bovine proteases and the corresponding enzyme
      from chickens were able to process the viral polyprotein containing LC3. Northern
      blots showed that bovine viral diarrhea virus infection of cells has no
      significant influence on the expression of either LC3 or its protease, bAut2B2.
      However, LC3-specific processing of the viral polyprotein containing the cellular
      insertion is essential for replication of the virus since mutants with changes in
      the LC3 insertion significantly affecting processing at the LC3/NS3 site were not
      viable.

PMID- 15140989
TI  - Intracellular targeting signals contribute to localization of coronavirus spike
      proteins near the virus assembly site.
AB  - Coronavirus budding at the endoplasmic reticulum-Golgi intermediate compartment
      (ERGIC) requires accumulation of the viral envelope proteins at this point in the
      secretory pathway. Here we demonstrate that the spike (S) protein from the group
      3 coronavirus infectious bronchitis virus (IBV) contains a canonical dilysine
      endoplasmic reticulum retrieval signal (-KKXX-COOH) in its cytoplasmic tail. This
      signal can retain a chimeric reporter protein in the ERGIC and when mutated
      allows transport of the full-length S protein as well as the chimera to the
      plasma membrane. Interestingly, the IBV S protein also contains a tyrosine-based
      endocytosis signal in its cytoplasmic tail, suggesting that any S protein that
      escapes the ERGIC will be rapidly endocytosed when it reaches the plasma
      membrane. We also identified a novel dibasic motif (-KXHXX-COOH) in the
      cytoplasmic tails of S proteins from group 1 coronaviruses and from the newly
      identified coronavirus implicated in severe acute respiratory syndrome. This
      dibasic motif also retained a reporter protein in the ERGIC, similar to the
      dilysine motif in IBV S. The cytoplasmic tails of S proteins from group 2
      coronaviruses lack an intracellular localization signal. The inherent differences
      in S-protein trafficking could point to interesting variations in pathogenesis of
      coronaviruses, since increased levels of surface S protein could promote
      syncytium formation and direct cell-to-cell spread of the infection.

PMID- 15140990
TI  - The level of virus-specific T-cell and macrophage recruitment in porcine
      reproductive and respiratory syndrome virus infection in pigs is independent of
      virus load.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important
      infectious disease agent of pigs worldwide, causing reproductive failure in
      pregnant sows and respiratory problems in nursing and growing pigs. PRRSV
      infection is characterized by a prolonged viremia of 30 or more days and an
      extended persistent infection of lymphoid tissues. To better understand the
      immunological basis for prolonged acute and persistent PRRSV infection, we have
      examined the cell-mediated immune (CMI) response throughout the course of
      infection and compared the results to the local distribution and abundance of
      PRRSV in infected tissues. PRRSV-specific T cells, enumerated by gamma interferon
      enzyme-linked immunospot assay, did not appear until 2 weeks after PRRSV
      inoculation, and their abundance exhibited substantial variation over time and
      among animals. In all cases the T-cell response was transient. High levels of
      viral RNA were present in lymphoid tissues of all animals in the acute phase of
      infection. Viral loads were decreased 1,000-fold or more in persistent
      infections, with the primary sites of persistence being tonsil, sternal lymph
      node, and inguinal lymph node. The abundance of virus-specific T cells in either
      acutely or persistently infected animals was highly variable and showed no
      correlation to the level of virus in lymphoid tissues. No significant difference
      in antigen-specific T-cell abundance was observed in secondary lymphoid tissues
      in either acute or persistent infection except for tonsil, in which the number of
      responding cells was extremely low. CD4(+)- and CD8(+)-T-cell frequencies did not
      change after PRRSV infection, though a decrease in gammadelta T cells was
      observed. Macrophages, the permissive cell type for PRRSV, were present in
      various levels in all tissue preparations and were not in proportion to local
      virus load. These findings indicate that a weak CMI response contributes to
      prolonged PRRSV infection and suggests that PRRSV suppresses T-cell recognition
      of infected macrophages. Thus, the slow but eventual resolution of PRRSV
      infection may be dependent on limiting permissive macrophages and on innate
      immune factors.

PMID- 15140991
TI  - Human papillomavirus type 16 E6 amino acid 83 variants enhance E6-mediated MAPK
      signaling and differentially regulate tumorigenesis by notch signaling and
      oncogenic Ras.
AB  - Oncogenically high-risk human papillomaviruses (HPVs) are causally associated
      with the progression of major human neoplasia-like cancers of the cervix. Several
      studies have defined functions of the key E6 and E7 oncoproteins in epithelial
      cell immortalization. The roles of these oncogenes in the progression of
      immortalized epithelial cells to invasive tumors are still poorly understood.
      Here, we establish a novel link between the E6 oncoprotein and activation of
      mitogen-activated protein kinase (MAPK) signaling and show that this signaling
      involves Rap1. We find that activated MAPK signaling cooperates with deregulated
      Notch1 signaling to recreate features of HPV-driven invasive cervical carcinomas.
      We extend our analysis to evaluate an E6 (amino acid [aa] 83) variant that has
      been linked to invasive tumors. The variant enhances MAPK signaling and
      cooperative transformation with deregulated Notch1 signaling. Unlike E6, this
      variant surprisingly inhibits oncogenic Ras-mediated transformation. Our data
      reveal that the quantitative differences in activation of MAPK signaling by E6
      and its variant correlate with differences in cooperative transformation with
      other signaling pathways, thus suggesting that thresholds of MAPK activation may
      define permissive conditions for other signaling pathways in tumorigenesis.
      Epidemiological studies have suggested the importance of E6 aa 83 variants in
      invasive carcinomas; our data support a key deterministic role for this variant
      in human cervical tumorigenesis. These observations, along with our recent data
      showing that deregulated Notch signaling activates phosphatidylinositol 3-kinase
      signaling, strengthen the possibility of the existence of Ras-independent
      mechanisms to recreate signaling through classical Ras effector pathways.

PMID- 15140992
TI  - Mutational analyses of Epstein-Barr virus glycoprotein 42 reveal functional
      domains not involved in receptor binding but required for membrane fusion.
AB  - Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with malignancies
      of both epithelial and lymphoid origin. Efficient infection of the latent host
      reservoir B lymphocytes involves the binding of glycoproteins gp350/220 for
      initial attachment, followed by the concerted action of gH, gL, gB, and gp42 for
      membrane fusion. The type II membrane protein gp42 is required for infection of B
      cells and assembles into a complex with gH and gL. The cellular host receptor for
      gp42, class II human leukocyte antigen (HLA), has been structurally verified by
      crystallization analyses of gp42 bound to HLA-DR1. Interestingly, the crystal
      structure revealed a hydrophobic pocket consisting of many aromatic and aliphatic
      residues from the predicted C-type lectin domain of gp42 that in other members of
      the C-type lectin family binds major histocompatibility complex class I or other
      diverse ligands. Although the hydrophobic pocket does not bind HLA class II,
      mutational analyses presented here indicate that this domain is essential for EBV
      induced membrane fusion. In addition, mutational analysis of the region of gp42
      contacting HLA class II in the gp42-HLA-DR1 cocrystal confirms that this region
      interacts with HLA class II and that this interaction is also important for EBV
      induced membrane fusion.

PMID- 15140993
TI  - Cleavage between replicase proteins p28 and p65 of mouse hepatitis virus is not
      required for virus replication.
AB  - The p28 and p65 proteins of mouse hepatitis virus (MHV) are the most amino
      terminal protein domains of the replicase polyprotein. Cleavage between p28 and
      p65 has been shown to occur in vitro at cleavage site 1 (CS1), (247)Gly downward
      arrow Val(248), in the polyprotein. Although critical residues for CS1 cleavage
      have been mapped in vitro, the requirements for cleavage have not been studied in
      infected cells. To define the determinants of CS1 cleavage and the role of
      processing at this site during MHV replication, mutations and deletions were
      engineered in the replicase polyprotein at CS1. Mutations predicted to allow
      cleavage at CS1 yielded viable virus that grew to wild-type MHV titers and showed
      normal expression and processing of p28 and p65. Mutant viruses containing
      predicted noncleaving mutations or a CS1 deletion were also viable but
      demonstrated delayed growth kinetics, reduced peak titers, decreased RNA
      synthesis, and small plaques compared to wild-type controls. No p28 or p65 was
      detected in cells infected with predicted noncleaving CS1 mutants or the CS1
      deletion mutant; however, a new protein of 93 kDa was detected. All introduced
      mutations and the deletion were retained during repeated virus passages in
      culture, and no phenotypic reversion was observed. The results of this study
      demonstrate that cleavage between p28 and p65 at CS1 is not required for MHV
      replication. However, proteolytic separation of p28 from p65 is necessary for
      optimal RNA synthesis and virus growth, suggesting important roles for these
      proteins in the formation or function of viral replication complexes.

PMID- 15140994
TI  - Helper-dependent adenovirus vectors elicit intact innate but attenuated adaptive
      host immune responses in vivo.
AB  - Helper-dependent adenovirus (HD-Ad) vectors with all adenoviral genes deleted
      mediate very long-term expression of therapeutic transgenes in a variety of
      animal models of disease. These vectors are associated with reduced toxicity and
      improved safety relative to traditional early region 1 deletion first-generation
      Ad (FG-Ad) vectors. Many studies have clearly demonstrated that FG-Ad vectors
      induce innate and adaptive immune responses in vivo; however, a comprehensive
      analysis of host immune responses to HD-Ad vectors has not yet been performed. In
      DBA/2 mice, intravenous injection of HD-Ad vectors encoding LacZ (HD-AdLacZ) or a
      murine secreted alkaline phosphatase (HD-AdSEAP) induced an early expression of
      inflammatory cytokine and chemokine genes in the liver, including interferon
      inducible protein 10, macrophage inflammatory protein 2, and tumor necrosis
      factor alpha, and were expressed in a pattern similar to that induced by FG-Ad
      vectors encoding AdSEAP. Like AdSEAP, and consistent with the pattern of cellular
      gene expression, HD-AdLacZ and HD-AdSEAP induced the recruitment of CD11b
      positive leukocytes to the transduced liver within hours of administration.
      AdSEAP also induced a second phase of liver inflammation, consisting of
      inflammatory gene expression and CD3-positive lymphocytic infiltrates 7 days
      posttransduction. In contrast, beyond 24 h no infiltrates or expression of
      inflammatory genes was detected in the livers of mice receiving HD-AdSEAP.
      Despite the lack of liver inflammation at 7 days, Ad-specific cytotoxic T
      lymphocytes could be detected in mice receiving HD-AdSEAP. This lack of liver
      inflammation was not due to reduced transduction since levels of transgene
      expression and the amounts of vector DNA in the liver were equivalent in mice
      receiving HD-AdSEAP and AdSEAP. These results demonstrate that HD-Ad vectors
      induce intact innate but attenuated adaptive immune responses in vivo.

PMID- 15140995
TI  - Intracellular topology and epitope shielding of poliovirus 3A protein.
AB  - The poliovirus RNA replication complex comprises multiple viral and possibly
      cellular proteins assembled on the cytoplasmic surface of rearranged
      intracellular membranes. Viral proteins 3A and 3AB perform several functions
      during the poliovirus replicative cycle, including significant roles in
      rearranging membranes, anchoring the viral polymerase to these membranes,
      inhibiting host protein secretion, and possibly providing the 3B protein primer
      for RNA synthesis. During poliovirus infection, the immunofluorescence signal of
      an amino-terminal epitope of 3A-containing proteins is markedly shielded compared
      to 3A protein expressed in the absence of other poliovirus proteins. This is not
      due to luminal orientation of all or a subset of the 3A-containing polypeptides,
      as shown by immunofluorescence following differential permeabilization and
      proteolysis experiments. Shielding of the 3A epitope is more pronounced in cells
      infected with wild-type poliovirus than in cells with temperature-sensitive
      mutant virus that contains a mutation in the 3D polymerase coding region adjacent
      to the 3AB binding site. Therefore, it is likely that direct binding of the
      poliovirus RNA-dependent RNA polymerase occludes the amino terminus of 3A
      containing polypeptides in the RNA replication complex.

PMID- 15140996
TI  - Passive immunotherapy in simian immunodeficiency virus-infected macaques
      accelerates the development of neutralizing antibodies.
AB  - Passively transferred neutralizing antibodies can block lentivirus infection, but
      their role in postexposure prophylaxis is poorly understood. In this nonhuman
      primate study, the effects of short-term antibody therapy on 5-year disease
      progression, virus load, and host immunity were explored. We reported previously
      that postinfection passive treatment with polyclonal immune globulin with high
      neutralizing titers against SIVsmE660 (SIVIG) significantly improved the 67-week
      health of SIVsmE660-infected Macaca mulatta macaques. Four of six treated
      macaques maintained low or undetectable levels of virus in plasma, compared with
      one of ten controls, while two rapid progressors controlled viremia only as long
      as the SIVIG was present. SIVIG treatment delayed the de novo production of
      envelope (Env)-specific antibodies by 8 weeks (13). We show here that differences
      in disease progression were also significant at 5 years postinfection, excluding
      rapid progressors (P = 0.05). Macaques that maintained </=10(3) virus particles
      per ml of plasma and </=30 infectious virus particles per 10(6) mononuclear cells
      from peripheral blood and lymph nodes had delayed disease onset. All macaques
      that survived beyond 18 months had measurable Gag-specific CD8(+) cytotoxic T
      cells, regardless of treatment. Humoral immunity in survivors beyond 20 weeks was
      strikingly different in the SIVIG and control groups. Despite a delay in Env
      specific binding antibodies, de novo production of neutralizing antibodies was
      significantly accelerated in SIVIG-treated macaques. Titers of de novo
      neutralizing antibodies at week 12 were comparable to levels achieved in controls
      only by week 32 or later. Acceleration of de novo simian immunodeficiency virus
      immunity in the presence of passively transferred neutralizing antibodies is a
      novel finding with implications for postexposure prophylaxis and vaccines.

PMID- 15140998
TI  - Species-specific tropism determinants in the human immunodeficiency virus type 1
      capsid.
AB  - Retroviral tropism is determined in part by cellular restriction factors that
      block infection by targeting the incoming viral capsid. Indeed, human
      immunodeficiency virus type 1 (HIV-1) infection of many nonhuman primate cells is
      inhibited by one such factor, termed Lv1. In contrast, a restriction factor in
      humans, termed Ref1, does not inhibit HIV-1 infection unless nonnatural mutations
      are introduced into the HIV-1 capsid protein (CA). Here, we examined the
      infectivity of a panel of mutant HIV-1 strains carrying substitutions in the N
      terminal CA domain in cells that exhibit restriction attributable to Lv1 or Ref1.
      Manipulation of HIV-1 CA could alter HIV-1 tropism, and several mutations were
      identified that increased or decreased HIV-1 infectivity in a target-cell
      specific manner. Many residues that affected HIV-1 tropism were located in the
      three variable loops that lie on the outer surface of the modeled HIV-1 conical
      capsid. Some tropism determinants, including the CypA binding site, coincided
      with residues whose mutation conferred on HIV-1 CA the ability to saturate Ref1
      in human cells. Notably, a mutation that reverses the infectivity defect in human
      cells induced by CypA binding site mutation inhibits recognition by Ref1.
      Overall, these findings demonstrate that exposed variable loops in CA and a
      partial CypA "coat" can modulate restriction and HIV-1 tropism and suggest a
      model in which the exposed surface of the incoming retroviral capsid is the
      target for inhibition by host cell-specific restriction factors.

PMID- 15140997
TI  - Cell-cell fusion induced by the avian reovirus membrane fusion protein is
      regulated by protein degradation.
AB  - The p10 fusion-associated small transmembrane protein of avian reovirus induces
      extensive syncytium formation in transfected cells. Here we show that p10-induced
      cell-cell fusion is restricted by rapid degradation of the majority of newly
      synthesized p10. The small ectodomain of p10 targets the protein for degradation
      following p10 insertion into an early membrane compartment. Paradoxically,
      conservative amino acid substitutions in the p10 ectodomain hydrophobic patch
      that eliminate fusion activity also increase p10 stability. The small amount of
      p10 that escapes intracellular degradation accumulates at the cell surface in a
      relatively stable form, where it mediates cell-cell fusion as a late-stage event
      in the virus replication cycle. The unusual relationship between a nonstructural
      viral membrane fusion protein and the replication cycle of a nonenveloped virus
      has apparently contributed to the evolution of a novel mechanism for restricting
      the extent of virus-induced cell-cell fusion.

PMID- 15140999
TI  - Human immunodeficiency virus type 1 Gag contains a dileucine-like motif that
      regulates association with multivesicular bodies.
AB  - Multivesicular bodies (MVBs) are cholesterol-enriched organelles formed by the
      endocytic pathway. The topology of vesicle formation in MVBs is identical to that
      of retroviral budding from the plasma membrane, and budding of human
      immunodeficiency virus type 1 (HIV-1) into MVBs in macrophages has recently been
      visualized. The Gag proteins from HIV-1, as well as many other retroviruses,
      contain short motifs that mediate interactions with MVBs and other endocytic
      components, suggesting that Gag proteins directly interface with the endocytic
      pathway. Here, we show that HIV-1 Gag contains an internalization signal that
      promotes endocytosis of a chimeric transmembrane fusion protein. Mutation of this
      motif within Gag strongly inhibits virus-like particle production. Moreover, wild
      type Gag, but not the internalization-defective mutation, can be induced to
      accumulate within CD63-positive MVBs by treatment of cells with U18666A, a drug
      that redistributes cholesterol from the plasma membrane to MVBs. We propose that
      HIV-1 Gag contains a signal that promotes interaction with the cellular endocytic
      machinery and that the site of particle production is regulated by the
      subcellular distribution of cholesterol.

PMID- 15141000
TI  - Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine
      enhanced disease induced by immunization with formalin-inactivated RSV.
AB  - Following respiratory syncytial virus (RSV) challenge, mice immunized with RSV G
      or with formalin-inactivated RSV (FI-RSV) exhibit severe disease associated with
      type 2 cytokine production and pulmonary eosinophilia. This has led to the
      proposal that the presence of RSV G is the factor in FI-RSV that induces disease
      enhancing T-cell responses. Therefore, we evaluated the role of RSV G and its
      immunodominant region in the induction of aberrant immune responses during FI-RSV
      immunization. BALB/c mice were immunized with FI preparations of wild-type (wt)
      RSV or recombinant RSV (rRSV) containing deletions of (i) the entire G gene, (ii)
      the region of the G gene encoding amino acids 187 to 197 of the immunodominant
      region, or (iii) the entire SH gene. After challenge, illness, RSV titers,
      cytokine levels, and pulmonary eosinophilia were measured. Peak RSV titers
      postchallenge were significantly greater in mice immunized with FI preparations
      of the deletion viruses than in those immunized with FI-rRSV wt, suggesting that
      the absence of G or SH in FI-RSV reduced its protective efficacy. Deletion of G
      or its epitope did not reduce illness, cytokine production, or eosinophilia
      relative to that in mice immunized with FI-rRSV wt. While cytokine levels and
      eosinophilia were similar, illness was reduced in mice immunized with SH-deleted
      FI-RSV. These data suggest that G-specific immune responses may be important for
      vaccine-induced protection and are not solely the basis for FI-RSV vaccine
      enhanced illness. These data suggest that the method of RSV antigen delivery,
      rather than the protein composition, influences the phenotype of the induced
      immune responses and that RSV G should not necessarily be excluded from potential
      vaccine strategies.

PMID- 15141001
TI  - Differential effects of interleukin-7 and interleukin-15 on NK cell anti-human
      immunodeficiency virus activity.
AB  - The ability of interleukin-7 (IL-7) and IL-15 to expand and/or augment effector
      cell functions may be of therapeutic benefit to human immunodeficiency virus
      (HIV)-infected patients. The functional effects of these cytokines on innate HIV
      specific immunity and their impact on cells harboring HIV are unknown. We
      demonstrate that both IL-7 and IL-15 augment natural killer (NK) function by
      using cells (CD3(-) CD16(+) CD56(+)) from both HIV-positive and -negative donors.
      Whereas IL-7 enhances NK function through upregulation of Fas ligand, the effect
      of IL-15 is mediated through upregulation of tumor necrosis factor-related
      apoptosis-inducing ligand. The difference in these effector mechanisms is
      reflected by the ability of IL-15-treated but not IL-7-treated NK cells to reduce
      the burden of replication-competent HIV in autologous peripheral blood
      mononuclear cells (PBMC) (infectious units per million for control NK cells,
      6.79; for IL-7-treated NK cells, 236.17; for IL-15-treated cells, 1.01; P = 0.01
      versus control). In addition, the treatment of PBMC with IL-15-treated but not IL
      7-treated NK cells causes undetectable HIV p24 (five of five cases), HIV RNA
      (five of five cases), or HIV DNA (three of five cases). These results support the
      concept of adjuvant immunotherapy of HIV infection with either IL-7 or IL-15 but
      suggest that the NK-mediated antiviral effect of IL-15 may be superior.

PMID- 15141002
TI  - Recombinant Sendai virus expressing the G glycoprotein of respiratory syncytial
      virus (RSV) elicits immune protection against RSV.
AB  - Although RSV causes serious pediatric respiratory disease, an effective vaccine
      does not exist. To capture the strengths of a live virus vaccine, we have used
      the murine parainfluenza virus type 1 (Sendai virus [SV]) as a xenogeneic vector
      to deliver the G glycoprotein of RSV. It was previously shown (J. L. Hurwitz, K.
      F. Soike, M. Y. Sangster, A. Portner, R. E. Sealy, D. H. Dawson, and C.
      Coleclough, Vaccine 15:533-540, 1997) that intranasal SV protected African green
      monkeys from challenge with the related human parainfluenza virus type 1 (hPIV1),
      and SV has advanced to clinical trials as a vaccine for hPIV1 (K. S. Slobod, J.
      L. Shenep, J. Lujan-Zilbermann, K. Allison, B. Brown, R. A. Scroggs, A. Portner,
      C. Coleclough, and J. L. Hurwitz, Vaccine, in press). Recombinant SV expressing
      RSV G glycoprotein was prepared by using reverse genetics, and intranasal
      inoculation of cotton rats elicited RSV-specific antibody and elicited protection
      from RSV challenge. RSV G-recombinant SV is thus a promising live virus vaccine
      candidate for RSV.

PMID- 15141003
TI  - Cleavage inhibition of the murine coronavirus spike protein by a furin-like
      enzyme affects cell-cell but not virus-cell fusion.
AB  - Cleavage of the mouse hepatitis coronavirus strain A59 spike protein was blocked
      in a concentration-dependent manner by a peptide furin inhibitor, indicating that
      furin or a furin-like enzyme is responsible for this process. While cell-cell
      fusion was clearly affected by preventing spike protein cleavage, virus-cell
      fusion was not, indicating that these events have different requirements.

PMID- 15141004
TI  - CD40-associated TRAF 6 signaling is required for disease induction in a
      retrovirus-induced murine immunodeficiency.
AB  - LP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy,
      hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named
      mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not
      mediate disease by upregulation of CD80 or CD86. We report here that there is
      nonetheless a necessity for CD40 signaling competence, specifically an intact
      tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.

PMID- 15141005
TI  - Reverse genetic analysis of the transcription regulatory sequence of the
      coronavirus transmissible gastroenteritis virus.
AB  - Coronavirus discontinuous transcription uses a highly conserved sequence (CS) in
      the joining of leader and body RNAs. Using a full-length infectious construct of
      transmissable gastroenteritis virus, the present study demonstrates that
      subgenomic transcription is heavily influenced by upstream flanking sequences and
      supports a mechanism of transcription attenuation that is regulated in part by a
      larger domain composed of primarily upstream flanking sequences which select
      appropriately positioned CS elements for synthesis of subgenomic RNAs.

PMID- 15141006
TI  - CKII site in Epstein-Barr virus nuclear protein 2 controls binding to hSNF5/Ini1
      and is important for growth transformation.
AB  - Substitution mutagenesis of EBNA2 shows that its interaction with hSNF5/Ini1
      involves two sites (286IPP and DQQ313), and a mutation at a CKII phosphorylation
      site (SS469) is essential for the interaction. An alanine substitution (SS469AA)
      prevents binding to EBNA2 and diminishes the growth-promotion potential of EBNA2
      in the transcomplementation assay.

PMID- 15141007
TI  - Human APOBEC3F is another host factor that blocks human immunodeficiency virus
      type 1 replication.
AB  - Recently, APOBEC3G has been identified as a host factor that blocks retroviral
      replication. It introduces G to A hypermutations in newly synthesized minus
      strand viral cDNA at the step of reverse transcription in target cells. Here, we
      identified the human APOBEC3F protein as another host factor that blocks human
      immunodeficiency virus type 1 (HIV-1) replication. Similar to APOBEC3G, APOBEC3F
      also induced G to A hypermutations in HIV genomic DNA, and the viral Vif protein
      counteracted its activity. Thus, APOBEC family members might have evolved as a
      general defense mechanism of the body against retroviruses, retrotransposons, and
      other mobile genetic elements.

PMID- 15141008
TI  - Apoptin/VP3 contains a concentration-dependent nuclear localization signal (NLS),
      not a tumorigenic selective NLS.

PMID- 15141009
TI  - Multiparametric evaluation of apoptosis: effects of standard cytotoxic agents and
      the cyanoguanidine CHS 828.
AB  - A multiparametric high-content screening assay for measurement of apoptosis was
      developed. HeLa cells and lymphoma U-937 cells were exposed to cytotoxic drugs in
      flat-bottomed optical microtiter plates. After incubation, the DNA-binding dye
      Hoechst 33342, fluorescein-tagged probes that covalently bind active caspases and
      chloromethyl-X-rosamine to detect mitochondrial membrane potential (MMP) were
      added. Image acquisition and quantitative measurement of fluorescence in a
      defined number of cells per well was performed using the automated image capture
      and analysis instrument ArrayScan. The usefulness of the assay was tested in
      cells exposed to standard cytotoxic drugs as well as in experimental cytotoxic
      cyanoguanidine CHS 828. A time- and dose-dependent activation of caspase-3,
      decrease in MMP, and increase in nuclear fragmentation and condensation were
      observed for the standard drugs, with the ability to correlate the parameters on
      a single cell basis. CHS 828 induced caspase-3 activation and reduction in MMP
      with modest changes in nuclear morphology. The method described was considered to
      be a rapid and information-rich apoptosis assay suitable both for correlating
      morphological and biochemical apoptotic events in single cells as well as for
      screening and evaluation of novel substances with apoptosis-inducing
      capabilities.

PMID- 15141010
TI  - The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in
      combination with STI571, delineates a spectrum of dependence of small cell lung
      cancer on IGF-I and stem cell factor signaling.
AB  - Stem cell factor (SCF)/Kit and insulin-like growth factor-I (IGF-I)/IGF-I
      receptor (IGF-IR) autocrine loops play a prominent role in the growth of small
      cell lung cancer (SCLC). Previous data suggested that IGF-I protects cells from
      apoptosis induced by STI571, an efficient inhibitor of Kit signal transduction,
      by activating the critical phosphatidylinositol 3-kinase-Akt pathway. To
      determine if inhibition of IGF-IR signaling would be therapeutically relevant in
      SCLC, the activity of a novel kinase inhibitor of IGF-IR, NVP-ADW742 (Novartis
      Pharma AG, Basel, Switzerland), was characterized. Pretreatment of the H526 cell
      line with NVP-ADW742 inhibited IGF-IR signaling and growth with IC(50) values
      between 0.1 and 0.4 micro M. SCF-mediated Kit phosphorylation and Akt activation
      were inhibited with IC(50) values in the 1-5 micro M range. However, NVP-ADW742
      affected neither hepatocyte growth factor-mediated Akt activation nor activity of
      constitutively active Akt. The therapeutic potential of NVP-ADW742 was assessed
      by determining its effect on growth of several SCLC cell lines in serum. These
      studies clearly delineated two populations of cell lines as determined by
      differential sensitivity to NVP-ADW742. One population, which lacks active
      SCF/Kit autocrine loops, was inhibited with IC(50) values between 0.1 and 0.5
      micro M. A second population, which has active SCF/Kit autocrine loops, was
      inhibited with IC(50) values in the 4-7 micro M range. When these cell lines were
      treated with a combination of STI571 and NVP-ADW742, no advantage was seen in the
      former group, whereas, in the latter group, a clearly synergistic response to the
      combination was seen when growth, apoptosis, or Akt activation was assessed.
      These data demonstrate that NVP-ADW742 is a potent and selective IGF-IR kinase
      inhibitor that can efficiently inhibit the growth of cells that are highly
      dependent on IGF-I signaling. However, for optimal growth inhibition of SCLC
      cells with an active SCF/Kit autocrine loop, a combination of a Kit inhibitor
      (STI571) and an IGF-IR inhibitor (NVP-ADW742) appears to be necessary. These
      observations suggest that, in tumors in which critical signal transduction
      pathways can be activated by alternative receptors, optimal therapy may require
      inhibition of multiple receptors.

PMID- 15141011
TI  - Photodynamic therapy with indocyanine green complements and enhances low-dose
      cisplatin cytotoxicity in MCF-7 breast cancer cells.
AB  - OBJECTIVE: We investigated the effects of photodynamic therapy (PDT) combined
      with low-dose chemotherapy on breast cancer cells. Photodynamic treatment was
      administered by irradiating indocyanine green-preloaded MCF-7 cells with an IR
      diode laser source at 805 nm; cisplatin was used for chemotherapy. METHODS: The
      dose-response phenomena associated with the two treatments administered
      individually and together were evaluated with the following tests: trypan blue
      dye exclusion, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT)
      assay, clonogenic survival, thymidine and methionine incorporation, and insulin
      dependent and insulin-independent glucose transport. RESULTS: Viability and
      metabolic data demonstrated mutual reinforcement of therapeutic efficacy.
      However, isobolographic analysis of quantal and variable data indicated that
      reinforcement was additive according to trypan blue data and synergistic
      according to MTT data. To investigate the molecular mechanisms underlying
      alterations in cell proliferation and apoptosis, we evaluated (by Western
      blotting) the expression of proteins Bcl-2, Bax, Bcl-X(L), p21, p53, and poly(ADP
      ribose) polymerase. Photodynamic treatment caused transient selective destruction
      of Bcl-2 and up-regulation of Bax. It also induced apoptosis in a limited
      fraction of cells (10-12%). Flow cytometry data showed that PDT killed mostly
      G(1)-phase cells, whereas cisplatin killed mostly S-phase cells. This disjointed
      phase-related effect may account for the favorable effects exerted by combined
      treatment. CONCLUSIONS: Our findings imply that low doses of cytostatic drugs may
      be as effective or even more effective than currently used doses if appropriately
      combined with PDT.

PMID- 15141012
TI  - Antisense oligonucleotides directed at the bcl-xl gene product augment
      chemotherapy response in mesothelioma.
AB  - OBJECTIVE: Malignant pleural mesothelioma (MPM) is resistant to both conventional
      chemotherapy and apoptosis. The bcl-2 family proteins are major determinants of
      apoptotic homeostasis. MPM lines and tumors routinely overexpress the anti
      apoptotic protein BCL-XL. We have previously shown that antisense inhibition of
      BCL-XL in MPM cells leads to apoptosis. We sought to determine whether antisense
      oligonucleotides directed at the bcl-xl gene product would augment response to a
      conventional chemotherapeutic agent in human mesothelioma cell lines. METHODS:
      The human MPM cell lines REN and I-45 were exposed to two bcl-xl antisense
      oligonucleotides (15999, 16009) and one sense oligonucleotide (113529) construct
      at varying doses, followed by IC(50) cisplatin. Cellular viability was assessed
      by a calorimetric assay, and apoptosis was evaluated by Hoechst staining, Annexin
      V staining, and sub-G(1) fluorescence-activated cell sorter analysis. Western
      blot analysis of BCL-2 family proteins was performed following single agent and
      combined treatment. Isobologram mathematical analysis was used to determine
      whether or not combination therapies were additive or synergistic. RESULTS: Cell
      viability was most affected with the 15999 antisense oligonucleotides plus IC(50)
      cisplatin combination (70% of I-45 and 90% of REN cells killed), and apoptosis
      was markedly increased with this combination by all measures. Western blot
      demonstrated 15999 antisense oligonucleotides construct down-regulation of BCL
      XL, but no further effect on expression of BCL-2 proteins with cisplatin.
      Isobologram analysis demonstrated 15999 + cisplatin synergistic effect.
      CONCLUSIONS: Exposure of human MPM cells to bcl-xl antisense oligonucleotides
      sensitizes human mesothelioma cells to the conventional chemotherapeutic agent
      cisplatin. Similar approaches using a combination of molecular and conventional
      treatment may have clinical utility for this tumor.

PMID- 15141013
TI  - Simultaneous inhibition of hsp 90 and the proteasome promotes protein
      ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and
      enhances antitumor activity.
AB  - The ansamycin antibiotic, geldanamycin, targets the hsp 90 protein chaperone and
      promotes ubiquitin-dependent proteasomal degradation of its numerous client
      proteins. Bortezomib is a specific and potent proteasome inhibitor. Both
      bortezomib and the geldanamycin analogue, 17-N-allylamino-17-demethoxy
      geldanamycin, are in separate clinical trials as new anticancer drugs. We
      hypothesized that destabilization of hsp 90 client proteins with geldanamycin,
      while blocking their degradation with bortezomib, would promote the accumulation
      of aggregated, ubiquitinated, and potentially cytotoxic proteins. Indeed,
      geldanamycin plus bortezomib inhibited MCF-7 tumor cell proliferation
      significantly more than either drug alone. Importantly, while control cells were
      unaffected, human papillomavirus E6 and E7 transformed fibroblasts were
      selectively sensitive to geldanamycin plus bortezomib. Geldanamycin alone
      slightly increased protein ubiquitination, but when geldanamycin was combined
      with bortezomib, protein ubiquitination was massively increased, beyond the
      amount stabilized by bortezomib alone. In geldanamycin plus bortezomib-treated
      cells, ubiquitinated proteins were mostly detergent insoluble, indicating that
      they were aggregated. Individually, both geldanamycin and bortezomib induced hsp
      90, hsp 70, and GRP78 stress proteins, but the drug combination superinduced
      these chaperones and caused them to become detergent insoluble. Geldanamycin plus
      bortezomib also induced the formation of abundant, perinuclear vacuoles, which
      were neither lysosomes nor autophagosomes and did not contain engulfed cytosolic
      ubiquitin or hsp 70. Fluorescence marker experiments indicated that these
      vacuoles were endoplasmic reticulum derived and that their formation was
      prevented by cycloheximide, suggesting a role for protein synthesis in their
      genesis. These observations support a mechanism whereby the geldanamycin plus
      bortezomib combination simultaneously disrupts hsp 90 and proteasome function,
      promotes the accumulation of aggregated, ubiquitinated proteins, and results in
      enhanced antitumor activity.

PMID- 15141014
TI  - Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent
      kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3
      human prostate cancer cells.
AB  - Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables,
      offers significant protection against cancer in animals induced by a variety of
      carcinogens. The present study demonstrates that PEITC suppresses proliferation
      of PC-3 cells in a dose-dependent manner by causing G(2)-M-phase cell cycle
      arrest and apoptosis. Interestingly, phenyl isothiocyanate (PITC), which is a
      structural analogue of PEITC but lacks the -CH(2) spacers that link the aromatic
      ring to the -N=C=S group, neither inhibited PC-3 cell viability nor caused cell
      cycle arrest or apoptosis. These results indicated that even a subtle change in
      isothiocyanate (ITC) structure could have a significant impact on its biological
      activity. The PEITC-induced cell cycle arrest was associated with a >80%
      reduction in the protein levels of cyclin-dependent kinase 1 (Cdk1) and cell
      division cycle 25C (Cdc25C; 24 h after treatment with 10 micro M PEITC), which
      led to an accumulation of Tyr(15) phosphorylated (inactive) Cdk1. On the other
      hand, PITC treatment neither reduced protein levels of Cdk1 or Cdc25C nor
      affected Cdk1 phosphorylation. The PEITC-induced decline in Cdk1 and Cdc25C
      protein levels and cell cycle arrest were significantly blocked on pretreatment
      of PC-3 cells with proteasome inhibitor lactacystin. A 24 h exposure of PC-3
      cells to 10 micro M PEITC, but not PITC, resulted in about 56% and 44% decrease
      in the levels of antiapoptotic proteins Bcl-2 and Bcl-X(L), respectively.
      However, ectopic expression of Bcl-2 failed to alter sensitivity of PC-3 cells to
      growth inhibition or apoptosis induction by PEITC. Treatment of cells with PEITC,
      but not PITC, also resulted in cleavage of procaspase-3, procaspase-9, and
      procaspase-8. Moreover, the PEITC-induced apoptosis was significantly attenuated
      in the presence of general caspase inhibitor and specific inhibitors of caspase-8
      and caspase-9. In conclusion, our data indicate that PEITC-induced cell cycle
      arrest in PC-3 cells is likely due to proteasome-mediated degradation of Cdc25C
      and Cdk1, and ectopic expression of Bcl-2 fails to confer resistance to PEITC
      induced apoptosis. Furthermore, the results of the present study point toward
      involvement of both caspase-8- and caspase-9-mediated pathways in apoptosis
      induction by PEITC.

PMID- 15141015
TI  - DNA damage responses triggered by a highly cytotoxic monofunctional DNA
      alkylator, hedamycin, a pluramycin antitumor antibiotic.
AB  - Long-term exposure (72 h) to hedamycin, a monofunctional DNA alkylator of the
      pluramycin class of antitumor antibiotics, decreased growth of mammalian cells by
      50% at subnanomolar concentrations. Short-term treatment (4 h) rapidly reduced
      DNA synthesis by 50% also at subnanomolar concentrations, but substantially
      higher levels were needed to block RNA synthesis while protein synthesis even at
      very high hedamycin concentrations remained unaffected. Hedamycin treatment at
      concentrations below its growth IC(50) induced only a transient and temporary
      accumulation of cells in G(2). Somewhat higher concentrations resulted in
      substantial S-phase arrest, and at increasing concentrations, complete cell cycle
      arrest in G(1) was observed without the appearance of a sub-G(1) cell population.
      Neither inhibition of cell growth nor cell cycle arrest appeared to be dependent
      on ataxia and Rad-related kinase expression. DNA damage checkpoint proteins
      including p53, chk1, and chk2 were differentially activated by hedamycin
      depending on the concentration and duration of treatment. The level of downstream
      cell cycle regulators such as cdc25A, E2F1, cyclin E, and p21 were also altered
      under conditions that induced cell cycle arrest, but atypically, p21
      overexpression was observed only in S-phase-arrested cells. Apoptotic indicators
      were only observed at moderate hedamycin concentrations associated with S-phase
      arrest, while increasing concentrations, when cells were arrested in G(1),
      resulted in a reduction of these signals. Taken together, the responses of cells
      to hedamycin are distinct with regard to its effect on cell cycle but also in the
      unusual concentration-dependent manner of activation of DNA damage and cell cycle
      checkpoint proteins as well as the induction of apoptotic-associated events.

PMID- 15141016
TI  - The novel estrogen 17alpha-20Z-21-[(4-amino)phenyl]-19-norpregna-1,3,5(10),20
      tetraene-3,17beta-diol induces apoptosis in prostate cancer cell lines at
      nanomolar concentrations in vitro.
AB  - Prostate cancer remains the number one cause of noncutaneous cancer, with 220,900
      new cases predicted for the year 2003 alone. Of the more promising classes of
      compounds studied thus far for the treatment of prostate cancer, estrogens of
      various types have consistently exhibited antitumor activities both in vitro and
      in vivo. For this reason, we have synthesized and screened a library of unique
      17alpha/11beta modified 17beta-estradiol (E(2)) analogues designed for estrogen
      receptor beta (ER-beta) specificity and a potential for cytotoxic activity
      directed toward prostate cancer cells. From this library, the novel compound
      17alpha-20Z-21-[(4-amino)phenyl]-19-norpregna-1,3,5(10),20-tetraene-3,17beta-diol
      (APVE(2)) was identified as the primary lead, found to induce a high level (>90%)
      of cell death through an apoptotic mechanism, with an EC(50) of 1.4, 2.7, and 16
      nM in the LNCaP, PC3, and DU145 cell lines, respectively. APVE(2) was found to
      bind to ER-beta, albeit weakly, with an EC(50) of 250 nM and a binding activity
      of 6.2% relative to E(2), nearly two orders of magnitude less than the
      concentration required to induce apoptosis. APVE(2) bound preferentially to ER
      beta by 7-fold over ER-alpha, and did not induce growth in the MCF-7 cell line,
      thus indicating that it is not a classical ER agonist. Furthermore, the cytotoxic
      actions of APVE(2) were not reversed by co-treatment with a 50-fold excess E(2).
      In summary, a novel 17 modified estrogen APVE(2) was identified as a lead
      compound, capable of inducing apoptosis in three prostate cancer cell lines at
      low nanomolar concentrations, through a mechanism inconsistent with an ER
      mediated mechanism.

PMID- 15141017
TI  - Disulfide-constrained peptides that bind to the extracellular portion of the
      prostate-specific membrane antigen.
AB  - The prostate-specific membrane antigen (PSMA) is a well-characterized surface
      antigen, overexpressed in the most advanced, androgen-resistant human prostate
      cancer cells. We sought to exploit PSMA cell surface properties as a target for
      short peptides that will potentially guide protein-based therapeutics, such as
      viral vectors, to prostate cancer cells. Two separate phage display peptide
      strategies were applied, in parallel, to purified PSMA protein bound to two
      separate substrates. We reasoned that peptide sequences common to both substrate
      selections would be specific binders of PSMA. Additionally, the design allowed
      for stringent cross-selections, where phage populations from one selection
      condition could be applied to the alternative substrate. These strategies
      resulted in a series of phage displayed peptides able to bind to PSMA by ELISA
      and direct binding assays, both with purified protein and in prostate cancer
      cells. Cell binding is competitively inhibited by purified PSMA. The synthesized
      peptides are capable of enhancing PSMA carboxypeptidase enzymatic activity,
      suggesting protein folding stabilization. The discovery of these peptides
      provides the foundation for subsequent development of peptide targeted
      therapeutics against prostate cancer.

PMID- 15141018
TI  - Methyl selenium metabolites decrease prostate-specific antigen expression by
      inducing protein degradation and suppressing androgen-stimulated transcription.
AB  - Prostate-specific antigen (PSA) is widely used clinically for prostate cancer
      diagnostics and as an indicator of therapeutic efficacy and recurrence. Several
      human chemoprevention trials are being conducted to validate the prostate cancer
      prevention efficacy of selenium and PSA is used in these trials as a biomarker of
      response. A better understanding of the effects of selenium metabolites on the
      kinetics of PSA turnover and secretion in prostate cancer cells treated with
      selenium at concentrations which are achievable physiologically will be important
      for interpreting the results of these trials. This study addresses whether the
      putative active anticancer selenium metabolite methylselenol or its precursor
      methylseleninic acid (MSeA) specifically inhibits PSA expression in the androgen
      responsive LNCaP prostate cancer cell model. The results show that exposure to
      sub-apoptotic concentrations of MSeA and methylselenol inhibited PSA protein
      expression and secretion, whereas sodium selenite and selenomethionine lacked
      inhibitory effect. The inhibition was detectable at 3 h of exposure and required
      a threshold level of MSeA to sustain. Turnover experiments showed that MSeA
      caused rapid PSA degradation, which was partially blocked by lysosomal
      inhibitors, but not by a proteasomal inhibitor. Furthermore, MSeA treatment
      reduced PSA mRNA level, down-regulated androgen receptor protein expression, and
      inhibited androgen-stimulated PSA promoter transcription. In summary,
      methylselenol or MSeA specifically and rapidly inhibited PSA expression through
      two mechanisms of action: inducing PSA protein degradation and suppressing
      androgen-stimulated PSA transcription. These findings may have important
      mechanistic implications for the prostate specific cancer chemopreventive action
      of selenium.

PMID- 15141019
TI  - Different DNA lesions trigger distinct cell death responses in HCT116 colon
      carcinoma cells.
AB  - The pleiotrophic cellular response to DNA damage includes activation of cell
      cycle checkpoints, induction of DNA repair pathways, and initiation of programmed
      cell death among others. The fate of cells with damaged DNA depends on the
      coordination of these different responses. The clinical efficacy of genotoxic
      therapies is influenced by cell fate and thus by how the DNA damage response is
      coordinated. While a great deal has been learned about how different DNA lesions
      activate distinct cell cycle checkpoints and DNA repair pathways, less is known
      about whether the type of DNA lesion influences the qualitative and quantitative
      nature of the cell death response. To address this question, HCT116 colon
      carcinoma cells have been treated with equally cytotoxic doses of the antitumor
      DNA alkylating agents adozelesin or bizelesin or the DNA strand scission agent C
      1027. The relative contribution of cell cycle arrest and cell death to measured
      cytotoxicity varied among the three drugs. Apoptotic cell death accounts for most
      C-1027 cytotoxicity while cell cycle arrest and cell death both contribute to the
      cytotoxicity of the alkylating agents. Each of the drugs induces a distinct but
      overlapping pattern of caspase activation. In addition, the cell death response
      to these drugs is differentially dependent on p53 and p21. These observations
      suggest that the type of DNA lesion influences not only the relative extent of
      apoptotic cell death at a given cytotoxic dose but also the qualitative nature of
      that response.

PMID- 15141020
TI  - Topoisomerase poisons differentially activate DNA damage checkpoints through
      ataxia-telangiectasia mutated-dependent and -independent mechanisms.
AB  - Camptothecin and Adriamycin are clinically important inhibitors for topoisomerase
      (Topo) I and Topo II, respectively. The ataxia-telangiectasia mutated (ATM)
      product is essential for ionizing radiation-induced DNA damage responses, but the
      role of ATM in Topo poisons-induced checkpoints remains unresolved. We found that
      distinct mechanisms are involved in the activation of different cell cycle
      checkpoints at different concentrations of Adriamycin and camptothecin.
      Adriamycin promotes the G(1) checkpoint through activation of the p53
      p21(CIP1/WAF1) pathway and decrease of pRb phosphorylation. Phosphorylation of
      p53(Ser20) after Adriamycin treatment is ATM dependent, but is not required for
      the full activation of p53. The G(1) checkpoint is dependent on ATM at low doses
      but not at high doses of Adriamycin. In contrast, the Adriamycin-induced G(2)
      checkpoint is independent on ATM but sensitive to caffeine. Adriamycin inhibits
      histone H3(Ser10) phosphorylation through inhibitory phosphorylation of CDC2 at
      low doses and down-regulation of cyclin B1 at high doses. The camptothecin
      induced intra-S checkpoint is partially dependent on ATM, and is associated with
      inhibitory phosphorylation of cyclin-dependent kinase 2 and reduction of BrdUrd
      incorporation after mid-S phase. Finally, apoptosis associated with high doses of
      Adriamycin or camptothecin is not influenced by the absence of ATM. These data
      indicate that the involvement of ATM following treatment with Topo poisons
      differs extensively with dosage and for different cell cycle checkpoints.

PMID- 15141021
TI  - Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells
      selected for resistance to natural product chemotherapy.
AB  - Resistance to natural product chemotherapy drugs is a major obstacle to
      successful cancer treatment. This type of resistance is often acquired in
      response to drug exposure; however, the mechanisms of this adverse reaction are
      complex and elusive. Here, we have studied acquired resistance to Adriamycin,
      Vinca alkaloids, and etoposide in MCF-7 breast cancer cells, KB-3-1 epidermoid
      carcinoma cells, and other cancer cell lines to determine if there is an
      association between expression of glucosylceramide synthase, the enzyme
      catalyzing ceramide glycosylation to glucosylceramide, and the multidrug
      resistant (MDR) phenotype. This work shows that glucosylceramide levels increase
      concomitantly with increased drug resistance in the KB-3-1 vinblastine-resistant
      sublines KB-V.01, KB-V.1, and KB-V1 (listed in order of increasing MDR). The
      levels of glucosylceramide synthase mRNA, glucosylceramide synthase protein, and
      P-glycoprotein (P-gp) also increased in parallel. Increased glucosylceramide
      levels were also present in Adriamycin-resistant KB-3-1 sublines KB-A.05 and KB
      A1. In breast cancer, detailed analysis of MCF-7 wild-type and MCF-7-AdrR cells
      (Adriamycin-resistant) demonstrated enhanced glucosylceramide synthase message
      and protein, P-gp message and protein, and high levels of glucosylceramide in
      resistant cells. Similar results were seen in vincristine-resistant leukemia,
      etoposide-resistant melanoma, and Adriamycin-resistant colon cancer cell lines.
      Cell-free glucosylceramide synthase activity was higher in lysates obtained from
      drug-resistant cells. Lastly, glucosylceramide synthase promoter activity was 15
      fold higher in MCF-7-AdrR compared with MCF-7 cells. We conclude that selection
      pressure for resistance to natural product chemotherapy drugs selects for
      enhanced ceramide metabolism through glucosylceramide synthase in addition to
      enhanced P-gp expression. A possible connection between glucosylceramide synthase
      and P-gp in drug resistance biology is suggested.

PMID- 15141022
TI  - Identification of human polo-like kinase 1 as a potential therapeutic target in
      pancreatic cancer.
AB  - Pancreas cancer is the fourth leading cause of cancer-related death in adults in
      the United States. New molecular targets for diagnosis and therapy of this
      disease are desperately needed. In this study, we report on the mitotic serine
      threonine kinase polo-like kinase 1 (Plk1) in pancreatic cancer. Plk1 mRNA was
      found to be overexpressed in 9 of 10 tested pancreatic cancer cell lines and in 4
      of 4 tested human tumors. Immunohistochemical staining of a pancreatic tissue
      microarray showed that 26 of the 35 tumors taken directly from patients
      overexpressed Plk1. We also examined the effects of depleting Plk1 in pancreatic
      cancer cells by the use of antisense oligonucleotides. Antisense-treated
      pancreatic cancer cells showed cell cycle arrest in G(2)-M as well as a drastic
      reduction in proliferation rates. These data suggest that Plk1 is a potential
      therapeutic target in devising a treatment for patients with pancreatic cancer.

PMID- 15141023
TI  - Hypoxia inducible factor-1alpha as a cancer drug target.
AB  - The hypoxia inducible factor 1 (HIF-1) is a heterodimeric transcription factor
      that is an important regulator of the growing tumor's response to hypoxia. HIF-1
      activity in tumors depends on the availability of the HIF-1alpha subunit, the
      levels of which increase under hypoxic conditions and through the activation of
      oncogenes and/or inactivation of tumor suppressor genes. HIF-1 activates genes
      that allow the cancer cell to survive and grow in the hostile hypoxic tumor
      environment. Increased tumor HIF-1alpha has been correlated with increased
      angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to the
      current interest in HIF-1alpha as a cancer drug target. A number of anticancer
      agents have been reported to decrease HIF-1alpha or HIF-1 transactivating
      activity in cells in culture. However, more relevant to the agents' antitumor
      activity is whether HIF-1 is inhibited in tumors in vivo. This has been
      demonstrated for only a few of the reported HIF-1 inhibitors. Some of the agents
      are moving toward clinical trial where it will be important to demonstrate that
      the agents inhibit HIF-1alpha in patient tumors or, failing this, the downstream
      consequences of HIF-1 inhibition such as decreased vascular endothelial growth
      factor formation, and relate this inhibition to antitumor activity. Only in this
      way will it be possible to determine if HIF-1alpha is a valid cancer drug target
      in humans.

PMID- 15141024
TI  - XRCC1-DNA polymerase beta interaction is required for efficient base excision
      repair.
AB  - X-ray repair cross-complementing protein-1 (XRCC1)-deficient cells are sensitive
      to DNA damaging agents and have delayed processing of DNA base lesions. In
      support of its role in base excision repair, it was found that XRCC1 forms a
      tight complex with DNA ligase IIIalpha and also interacts with DNA polymerase
      beta (Pol beta) and other base excision repair (BER) proteins. We have isolated
      wild-type XRCC1-DNA ligase IIIalpha heterodimer and mutated XRCC1-DNA ligase
      IIIalpha complex that does not interact with Pol beta and tested their activities
      in BER reconstituted with human purified proteins. We find that a point mutation
      in the XRCC1 protein which disrupts functional interaction with Pol beta,
      affected the ligation efficiency of the mutant XRCC1-DNA ligase IIIalpha
      heterodimer in reconstituted BER reactions. We also compared sensitivity to
      hydrogen peroxide between wild-type CHO-9 cells, XRCC1-deficient EM-C11 cells and
      EM-C11 cells transfected with empty plasmid vector or with plasmid vector
      carrying wild-type or mutant XRCC1 gene and find that the plasmid encoding XRCC1
      protein, that does not interact with Pol beta has reduced ability to rescue the
      hydrogen peroxide sensitivity of XRCC1- deficient cells. These data suggest an
      important role for the XRCC1-Pol beta interaction for coordinating the efficiency
      of the BER process.

PMID- 15141025
TI  - Preferential binding to branched DNA strands and strand-annealing activity of the
      human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex.
AB  - The Rad51B, Rad51C, Rad51D and Xrcc2 proteins are Rad51 paralogs, and form a
      complex (BCDX2 complex) in mammalian cells. Mutant cells defective in any one of
      the Rad51-paralog genes exhibit spontaneous genomic instability and extreme
      sensitivity to DNA-damaging agents, due to inefficient recombinational repair.
      Therefore, the Rad51 paralogs play important roles in the maintenance of genomic
      integrity through recombinational repair. In the present study, we examined the
      DNA-binding preference of the human BCDX2 complex. Competitive DNA-binding assays
      using seven types of DNA substrates, single-stranded DNA (ssDNA), double-stranded
      DNA, 5'- and 3'-tailed duplexes, nicked duplex DNA, Y-shaped DNA and a synthetic
      Holliday junction, revealed that the BCDX2 complex preferentially bound to the
      two DNA substrates with branched structures (the Y-shaped DNA and the synthetic
      Holliday junction). Furthermore, the BCDX2 complex catalyzed the strand-annealing
      reaction between a long linear ssDNA (1.2 kb in length) and its complementary
      circular ssDNA. These properties of the BCDX2 complex may be important for its
      roles in the maintenance of chromosomal integrity.

PMID- 15141026
TI  - Predicting transmembrane beta-barrels in proteomes.
AB  - Very few methods address the problem of predicting beta-barrel membrane proteins
      directly from sequence. One reason is that only very few high-resolution
      structures for transmembrane beta-barrel (TMB) proteins have been determined thus
      far. Here we introduced the design, statistics and results of a novel profile
      based hidden Markov model for the prediction and discrimination of TMBs. The
      method carefully attempts to avoid over-fitting the sparse experimental data.
      While our model training and scoring procedures were very similar to a recently
      published work, the architecture and structure-based labelling were significantly
      different. In particular, we introduced a new definition of beta- hairpin motifs,
      explicit state modelling of transmembrane strands, and a log-odds whole-protein
      discrimination score. The resulting method reached an overall four-state (up-,
      down-strand, periplasmic-, outer-loop) accuracy as high as 86%. Furthermore,
      accurately discriminated TMB from non-TMB proteins (45% coverage at 100%
      accuracy). This high precision enabled the application to 72 entirely sequenced
      Gram-negative bacteria. We found over 164 previously uncharacterized TMB proteins
      at high confidence. Database searches did not implicate any of these proteins
      with membranes. We challenge that the vast majority of our 164 predictions will
      eventually be verified experimentally. All proteome predictions and the PROFtmb
      prediction method are available at http://www.rostlab.org/ services/PROFtmb/.

PMID- 15141027
TI  - Functions of yeast helicase Ssl2p that are essential for viability are also
      involved in protection from the toxicity of adriamycin.
AB  - We have found that, in the yeast Saccharomyces cerevisiae, overexpression of the
      DNA helicase Ssl2p confers resistance to adriamycin. Ssl2p is involved, as a
      subunit of the basic transcription factor TFIIH, in the initiation of
      transcription and in nucleotide-excision repair (NER), and this helicase is
      essential for the survival of yeast cells. An examination of the relationship
      between the known functions of Ssl2p and adriamycin resistance indicated that
      overexpression of Ssl2p caused little or no increase in the rate of RNA synthesis
      and in NER. The absence of any involvement of NER in adriamycin resistance was
      supported by the finding that yeast cells that overexpressed the mutant form of
      Ssl2p that lacked the carboxy-terminal region, which is necessary for NER,
      remained resistant to adriamycin. When we examined the effects of overexpression
      in yeast of other mutant forms of Ssl2p with various deletions, we found that, of
      the 843 amino acids of Ssl2p, the entire amino acid sequence from position 81 to
      position 750 was necessary for adriamycin resistance. This region is identical to
      the region of Ssl2p that is necessary for the survival of yeast cells. Although
      this region contains helicase motifs, the overexpression of other yeast
      helicases, such as Rad3 and Sgs1, had little or no effect on adriamycin
      resistance, indicating that a mere increase in the intracellular level of
      helicases does not result in adriamycin resistance. Our results suggest that the
      functions of Ssl2p that are essential for yeast survival are also required for
      protection against adriamycin toxicity.

PMID- 15141028
TI  - Hepatocyte nuclear factor 4alpha enhances the hepatocyte nuclear factor 1alpha
      mediated activation of transcription.
AB  - Hepatocyte Nuclear Factor 1alpha (HNF1alpha) and Hepatocyte Nuclear Factor 4alpha
      (HNF4alpha) are two liver-enriched transcription factors coexpressed in specific
      tissues where they play a crucial role through their involvement in a complex
      cross-regulatory network. HNF1alpha down regulates HNF4alpha-mediated activation
      of transcription via a direct protein-protein interaction. Here we show that
      HNF4alpha enhances the transcriptional activity of HNF1alpha in a DNA binding
      independent manner, thus indicating that it behaves as a HNF1alpha coactivator.
      Using mutations in the ligand binding domain (LBD) of HNF4alpha, we confirmed the
      involvement of the Activation Function 2 module and demonstrated the requirement
      of the integrity of the LBD for the interaction with HNF1alpha. Moreover, we show
      that HNF4alpha cooperates with p300 to achieve the highest HNF1alpha-mediated
      transcription rates. Our findings highlight a new way by which HNF4alpha can
      regulate gene expression and extend our knowledge of the complexity of the
      transcriptional network involving HNF4alpha and HNF1alpha.

PMID- 15141029
TI  - Mapping of the second tetracycline binding site on the ribosomal small subunit of
      E.coli.
AB  - Tetracycline blocks stable binding of aminoacyl-tRNA to the bacterial ribosomal A
      site. Various tetracycline binding sites have been identified in crystals of the
      30S ribosomal small subunit of Thermus thermophilus. Here we describe a direct
      photo- affinity modification of the ribosomal small subunits of Escherichia coli
      with 7-[3H]-tetracycline. To select for specific interactions, an excess of the
      30S subunits over tetracycline has been used. Primer extension analysis of the
      16S rRNA revealed two sites of the modifications: C936 and C948. Considering
      available data on tetracycline interactions with the prokaryotic 30S subunits,
      including the presented data (E.coli), X-ray data (T.thermophilus) and genetic
      data (Helicobacter pylori, E.coli), a second high affinity tetracycline binding
      site is proposed within the 3'-major domain of the 16S rRNA, in addition to the A
      site related tetracycline binding site.

PMID- 15141031
TI  - Synapsis and DNA cleavage in phiC31 integrase-mediated site-specific
      recombination.
AB  - The Streptomyces phage phiC31 encodes an integrase belonging to the serine
      recombinase family of site-specific recombinases. The well studied serine
      recombinases, the resolvase/invertases, bring two recombination sites together in
      a synapse, and then catalyse a concerted four-strand staggered break in the DNA
      substrates whilst forming transient covalent attachments with the recessed 5'
      ends. Rotation of one pair of half sites by 180 degrees relative to the other
      pair occurs, to form the recombinant configuration followed by ligation of the
      DNA backbone. Here we address the nature of the recombination intermediates
      formed by phiC31 integrase when acting on its substrates attP and attB. We have
      identified intermediates containing integrase covalently attached to cleaved DNA
      substrates, attB or attP, by analysis of complexes in gels and after treatment of
      these complexes with proteinases. Using a catalytically inactive integrase
      mutant, S12A, the synaptic complexes containing integrase, attP and attB were
      identified. Furthermore, we have shown that attB mutants containing insertions or
      deletions are blocked in recombination at the stage of strand cleavage. Thus,
      there is a strict spacing requirement within attB, possibly for correct
      positioning of the catalytic serine relative to the scissile phosphate in the
      active site. Finally, using integrase S12A we confirmed the inability of attL and
      attR or other combinations of sites to form a stable synapse, indicating that the
      directionality of integrative recombination is determined at synapsis.

PMID- 15141032
TI  - A Fugu-Human Genome Synteny Viewer: web software for graphical display and
      annotation reports of synteny between Fugu genomic sequence and human genes.
AB  - A web server has been developed to access annotation and graphical reports of
      synteny and gene order between the Fugu genome and human genes. In this system,
      the assembled Fugu genomic sequences (also known as scaffolds) are annotated. The
      annotations for each Fugu scaffold are computed, stored and made publicly
      available. The annotations describe matches to human homologous genes. For each
      significant human gene match on the Fugu scaffold, the corresponding human
      chromosome map and measures of the significance of each match are given. The web
      based server provides public access to these annotations and graphical displays
      of the results. The user is provided with a selection of views including a
      chromosome-colour-coded image and a table containing the details of the matches.
      The Fugu-Human Genome Synteny Viewer has been tested by comparing results with
      examples from a paper that includes a study of transcription factors, Fos and Jun
      encoding regions. The Fugu-human genome synteny views are available for each Fugu
      scaffold through the clonesearch web page located at the Fugu Genomics website
      (http://fugu.rfcgr.mrc.ac.uk/).

PMID- 15141030
TI  - Influence of loop size on the stability of intramolecular DNA quadruplexes.
AB  - We have determined the stability of intramolecular DNA quadruplexes in which the
      four G(3)-tracts are connected by non-nucleosidic linkers containing propanediol,
      octanediol or hexaethylene glycol, replacing the TTA loops in the human telomeric
      repeat sequence. We find that these sequences all fold to form intramolecular
      complexes, which are stabilized by lithium < sodium < potassium. Quadruplex
      stability increases in the order propanediol < hexaethylene glycol < octanediol.
      The shallower shape of the melting profile with propanediol linkers and its lower
      dependency on potassium concentration suggests that this complex contains fewer
      stacks of G-quartets. The sequence with octanediol linkers displays a biphasic
      melting profile, suggesting that it can adopt more than one stable structure. All
      these complexes display melting temperatures above 310 K in the presence of 10 mM
      lithium, without added potassium, in contrast to the telomeric repeat sequence.
      These complexes also fold much faster than the telomeric repeat and there is
      little or no hysteresis between their melting and annealing profiles. In
      contrast, the human telomeric repeat sequence and a complex containing two
      hexaethylene glycol groups in each loop, are less stable and fold more slowly.
      The melting and annealing profiles for the latter sequence show significant
      differences, even when heated at 0.2 degrees C min(-1). CD spectra for the
      oligonucleotides containing non-nucleosidic linkers show positive maxima at 264
      nm, with negative minima approximately 244 nm, which are characteristic of
      parallel quadruplex structures. These results show that the structure and
      stability of intramolecular quadruplexes is profoundly influenced by the length
      and composition of the loops.

PMID- 15141033
TI  - The hepatitis C virus Core protein is a potent nucleic acid chaperone that
      directs dimerization of the viral (+) strand RNA in vitro.
AB  - The hepatitis C virus (HCV) is an important human pathogen causing chronic
      hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped
      virus with a positive-sense, single-stranded RNA genome encoding a single
      polyprotein that is processed to generate viral proteins. Several hundred
      molecules of the structural Core protein are thought to coat the genome in the
      viral particle, as do nucleocapsid (NC) protein molecules in Retroviruses,
      another class of enveloped viruses containing a positive-sense RNA genome.
      Retroviral NC proteins also possess nucleic acid chaperone properties that play
      critical roles in the structural remodelling of the genome during retrovirus
      replication. This analogy between HCV Core and retroviral NC proteins prompted us
      to investigate the putative nucleic acid chaperoning properties of the HCV Core
      protein. Here we report that Core protein chaperones the annealing of
      complementary DNA and RNA sequences and the formation of the most stable duplex
      by strand exchange. These results show that the HCV Core is a nucleic acid
      chaperone similar to retroviral NC proteins. We also find that the Core protein
      directs dimerization of HCV (+) RNA 3' untranslated region which is promoted by a
      conserved palindromic sequence possibly involved at several stages of virus
      replication.

PMID- 15141034
TI  - Mismatch cleavage by single-strand specific nucleases.
AB  - We have investigated the ability of single-strand specific (sss) nucleases from
      different sources to cleave single base pair mismatches in heteroduplex DNA
      templates used for mutation and single-nucleotide polymorphism analysis. The
      TILLING (Targeting Induced Local Lesions IN Genomes) mismatch cleavage protocol
      was used with the LI-COR gel detection system to assay cleavage of amplified
      heteroduplexes derived from a variety of induced mutations and naturally
      occurring polymorphisms. We found that purified nucleases derived from celery
      (CEL I), mung bean sprouts and Aspergillus (S1) were able to specifically cleave
      nearly all single base pair mismatches tested. Optimal nicking of heteroduplexes
      for mismatch detection was achieved using higher pH, temperature and divalent
      cation conditions than are routinely used for digestion of single-stranded DNA.
      Surprisingly, crude plant extracts performed as well as the highly purified
      preparations for this application. These observations suggest that diverse
      members of the S1 family of sss nucleases act similarly in cleaving non
      specifically at bulges in heteroduplexes, and single-base mismatches are the
      least accessible because they present the smallest single-stranded region for
      enzyme binding. We conclude that a variety of sss nucleases and extracts can be
      effectively used for high-throughput mutation and polymorphism discovery.

PMID- 15141035
TI  - Localization and dynamics of small circular DNA in live mammalian nuclei.
AB  - While genomic DNA, packaged into chromatin, is known to be locally constrained
      but highly dynamic in the nuclei of living cells, little is known about the
      localization and dynamics of small circular DNA molecules that invade cells by
      virus infection, application of gene therapy vectors or experimental
      transfection. To address this point, we have created traceable model substrates
      by direct labeling of plasmid DNA with fluorescent peptide nucleic acids, and
      have investigated their fate after microinjection into living cells. Here, we
      report that foreign DNA rapidly undergoes interactions with intranuclear
      structural sites that strongly reduce its mobility and restrict the DNA to
      regions excluding nucleoli and nuclear bodies such as PML bodies. The labeled
      plasmids partially co-localize with SAF-A, a well characterized marker protein
      for the nuclear 'scaffold' or 'matrix', and are resistant towards extraction by
      detergent and, in part, elevated salt concentrations. We show that the
      localization and the low mobility of plasmids is independent of the plasmid
      sequence, and does not require the presence of either a scaffold attachment
      region (SAR) DNA element or a functional promoter.

PMID- 15141036
TI  - Expression of the adenovirus E4 34k oncoprotein inhibits repair of double strand
      breaks in the cellular genome of a 293-based inducible cell line.
AB  - The human adenovirus E4 ORF 6 34 kDa oncoprotein (E4 34k), in concert with the 55
      kDa product of E1b, prevents concatenation of viral genomes in infected cells,
      inhibits the repair of double strand breaks (DSBs) in the viral genome, and
      inhibits V(D)J recombination in a plasmid transfection assay. These activities
      are consistent with a general inhibition by the E4 34k and E1b 55k proteins of
      DSB repair by non-homologous end joining (NHEJ) on extrachromosomal substrates.
      To determine whether inhibition of NHEJ extends to repair of DSBs in the cell
      chromosome, we have examined the effects of E4 34k on repair of chromosomal DSBs
      induced by ionizing radiation in a cell line in which E4 34k expression and
      biological activity is inducible and E1b 55k is produced constitutively. We
      demonstrate that in this cell line, induction of E4 34k inhibits chromosomal DSB
      repair. Recently, it has been shown that in infected cells, E4 34k and the
      adenovirus E1b 55k proteins cooperate to destabilize Mre11 and Rad50, components
      of mammalian NHEJ systems. Consistent with this, induction of expression of E4
      34k in the inducible cell line also reduces the steady state level of Mre11
      protein.

PMID- 15141038
TI  - Index case.

PMID- 15141039
TI  - "I swear by Apollo"--on taking the Hippocratic oath.

PMID- 15141037
TI  - Pharmacological and genetic modulation of Wnt-targeted Cre-Lox-mediated gene
      expression in colorectal cancer cells.
AB  - Wnt-targeted gene therapy has been proposed as a treatment for human colorectal
      cancer (CRC). The Cre-Lox system consists of methodology for enhancing targeted
      expression from tissue-specific or cancer-specific promoters. We analyzed the
      efficiency of Wnt-specific promoters as drivers of the Cre-mediated activity of a
      luciferase reporter gene or cell death effector gene in CRC cell lines in the
      presence and absence of two modulators of Wnt activity, sodium butyrate and
      lithium chloride. Butyrate is present in the colonic lumen after digestion of
      fiber-rich foods, whereas the colonic lumen is readily accessible to lithium
      chloride. In both SW620 and HCT-116 CRC cells, a physiologically relevant
      concentration of butyrate upregulated reporter and effector activity and altered
      the Wnt-specific expression pattern. Lithium chloride markedly enhanced Cre-Lox
      mediated Wnt-specific reporter expression only in APC wild-type CRC cells.
      Possibilities for genetic modulation of the proposed CRC therapy included Wnt
      specific expression of a floxed Lef1-VP16 fusion that enhanced Wnt-specific cell
      death and of a floxed dominant-negative Tcf4 that specifically downregulated
      endogenous Wnt activity. These findings demonstrated that the Cre-Lox system, in
      combination with pharmacological and genetic modulators, represents effective
      methodology for enhancing Wnt-targeted gene therapy.

PMID- 15141040
TI  - Dying and decision making--evolution of end-of-life options.

PMID- 15141041
TI  - Homocysteine levels and the risk of osteoporotic fracture.
AB  - BACKGROUND: Very high plasma homocysteine levels are characteristic of
      homocystinuria, a rare autosomal recessive disease accompanied by the early onset
      of generalized osteoporosis. We therefore hypothesized that mildly elevated
      homocysteine levels might be related to age-related osteoporotic fractures.
      METHODS: We studied the association between circulating homocysteine levels and
      the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or
      older, who participated in two separate prospective, population-based studies. In
      the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort
      1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with
      a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam,
      there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7
      years. Multivariate Cox proportional-hazards regression models were used for
      analysis of the risk of fracture, with adjustment for age, sex, body-mass index,
      and other characteristics that may be associated with the risk of fracture or
      with increased homocysteine levels. RESULTS: During 11,253 person-years of follow
      up, osteoporotic fractures occurred in 191 subjects. The overall multivariable
      adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2
      to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine
      level. The risk was similar in all three cohorts studied, and it was also similar
      in men and women. A homocysteine level in the highest age-specific quartile was
      associated with an increase by a factor of 1.9 in the risk of fracture (95
      percent confidence interval, 1.4 to 2.6). The associations between homocysteine
      levels and the risk of fracture appeared to be independent of bone mineral
      density and other potential risk factors for fracture. CONCLUSIONS: An increased
      homocysteine level appears to be a strong and independent risk factor for
      osteoporotic fractures in older men and women.

PMID- 15141042
TI  - Homocysteine as a predictive factor for hip fracture in older persons.
AB  - BACKGROUND: The increased prevalence of osteoporosis among people with
      homocystinuria suggests that a high serum homocysteine concentration may weaken
      bone by interfering with collagen cross-linking, thereby increasing the risk of
      osteoporotic fracture. We examined the association between the total homocysteine
      concentration and the risk of hip fracture in men and women enrolled in the
      Framingham Study. METHODS: We studied 825 men and 1174 women, ranging in age from
      59 to 91 years, from whom blood samples had been obtained between 1979 and 1982
      to measure plasma total homocysteine. The participants in our study were followed
      from the time that the sample was obtained through June 1998 for incident hip
      fracture. Sex-specific, age-adjusted incidence rates of hip fracture were
      calculated for quartiles of total homocysteine concentrations. Cox proportional
      hazards regression was used to calculate hazard ratios for quartiles of
      homocysteine values. RESULTS: The mean (+/-SD) plasma total homocysteine
      concentration was 13.4+/-9.1 micromol per liter in men and 12.1+/-5.3 micromol
      per liter in women. The median duration of follow-up was 12.3 years for men and
      15.0 years for women. There were 41 hip fractures among men and 146 among women.
      The age-adjusted incidence rates per 1000 person-years for hip fracture, from the
      lowest to the highest quartile for total homocysteine, were 1.96 (95 percent
      confidence interval, 0.52 to 3.41), 3.24 (0.97 to 5.52), 4.43 (1.80 to 7.07), and
      8.14 (4.20 to 12.08) for men and 9.42 (5.72 to 13.12), 7.01 (4.29 to 9.72), 9.58
      (6.42 to 12.74), and 16.57 (11.84 to 21.30) for women. Men and women in the
      highest quartile had a greater risk of hip fracture than those in the lowest
      quartile--the risk was almost four times as high for men and 1.9 times as high
      for women. CONCLUSIONS: These findings suggest that the homocysteine
      concentration, which is easily modifiable by means of dietary intervention, is an
      important risk factor for hip fracture in older persons.

PMID- 15141043
TI  - A comparison of laparoscopically assisted and open colectomy for colon cancer.
AB  - BACKGROUND: Minimally invasive, laparoscopically assisted surgery was first
      considered in 1990 for patients undergoing colectomy for cancer. Concern that
      this approach would compromise survival by failing to achieve a proper oncologic
      resection or adequate staging or by altering patterns of recurrence (based on
      frequent reports of tumor recurrences within surgical wounds) prompted a
      controlled trial evaluation. METHODS: We conducted a noninferiority trial at 48
      institutions and randomly assigned 872 patients with adenocarcinoma of the colon
      to undergo open or laparoscopically assisted colectomy performed by credentialed
      surgeons. The median follow-up was 4.4 years. The primary end point was the time
      to tumor recurrence. RESULTS: At three years, the rates of recurrence were
      similar in the two groups--16 percent among patients in the group that underwent
      laparoscopically assisted surgery and 18 percent among patients in the open
      colectomy group (two-sided P=0.32; hazard ratio for recurrence, 0.86; 95 percent
      confidence interval, 0.63 to 1.17). Recurrence rates in surgical wounds were less
      than 1 percent in both groups (P=0.50). The overall survival rate at three years
      was also very similar in the two groups (86 percent in the laparoscopic-surgery
      group and 85 percent in the open-colectomy group; P=0.51; hazard ratio for death
      in the laparoscopic-surgery group, 0.91; 95 percent confidence interval, 0.68 to
      1.21), with no significant difference between groups in the time to recurrence or
      overall survival for patients with any stage of cancer. Perioperative recovery
      was faster in the laparoscopic-surgery group than in the open-colectomy group, as
      reflected by a shorter median hospital stay (five days vs. six days, P<0.001) and
      briefer use of parenteral narcotics (three days vs. four days, P<0.001) and oral
      analgesics (one day vs. two days, P=0.02). The rates of intraoperative
      complications, 30-day postoperative mortality, complications at discharge and 60
      days, hospital readmission, and reoperation were very similar between groups.
      CONCLUSIONS: In this multi-institutional study, the rates of recurrent cancer
      were similar after laparoscopically assisted colectomy and open colectomy,
      suggesting that the laparoscopic approach is an acceptable alternative to open
      surgery for colon cancer.

PMID- 15141044
TI  - Priorities for the treatment of latent tuberculosis infection in the United
      States.
AB  - BACKGROUND: The prevention of active tuberculosis through the treatment of latent
      tuberculosis infection is a major element of the national strategy for
      eliminating tuberculosis in the United States. Targeted treatment for persons who
      are at the highest risk for reactivation tuberculosis will be needed to achieve
      this goal. A more precise assessment of the lifetime risk of reactivation
      tuberculosis, usually estimated at 5 to 10 percent, could help to identify
      patients who are at the highest risk and motivate them to complete treatment.
      Currently, the rate of completion of treatment is low. METHODS: Published reports
      were reviewed to obtain estimates of the risk of tuberculosis among persons with
      a positive tuberculin skin test. Using these data, I constructed a model to
      estimate the lifetime risk of tuberculosis among persons with specific medical
      conditions. RESULTS: The lifetime risk of reactivation tuberculosis is 20 percent
      or more among most persons with induration of 10 mm or more on a tuberculin skin
      test and either human immunodeficiency virus infection or evidence of old, healed
      tuberculosis. The lifetime risk is 10 to 20 percent among persons with recent
      conversion of a tuberculin skin test and among most persons younger than 35 years
      of age who are receiving infliximab therapy and have induration of 15 mm or more
      on a tuberculin skin test. The risk is also 10 to 20 percent among children five
      years of age or younger who have induration of 10 mm or more on a tuberculin skin
      test. CONCLUSIONS: Persons with these characteristics should be targeted for
      intensive efforts to ensure full treatment of latent tuberculosis. Improved rates
      of completion of treatment among such persons could help to eliminate
      tuberculosis in the United States.

PMID- 15141045
TI  - Autoimmune polyendocrine syndromes.

PMID- 15141046
TI  - Images in clinical medicine. Stretch brachial plexopathy.

PMID- 15141047
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 15-2004. A 31-year-old man with bilateral testicular enlargement.

PMID- 15141049
TI  - Laparoscopic resection for colon cancer--the end of the beginning?

PMID- 15141048
TI  - Homocysteine and osteoporotic fractures--culprit or bystander?

PMID- 15141050
TI  - The molecular basis of streptococcal toxic shock syndrome.

PMID- 15141051
TI  - Changing the priority for HLA matching in kidney transplantation.

PMID- 15141052
TI  - High-bone-mass disease and LRP5.

PMID- 15141053
TI  - Paclitaxel-eluting coronary stents.

PMID- 15141054
TI  - "Me-too" products--friend or foe?

PMID- 15141055
TI  - Antiplatelet therapy for ischemic heart disease.

PMID- 15141056
TI  - Acute chemical emergencies.

PMID- 15141057
TI  - Islet transplantation as a treatment for diabetes.

PMID- 15141058
TI  - Infectious tuberculosis among newly arrived refugees in the United States.

PMID- 15141059
TI  - Images in clinical medicine. Papilledema and spinal cord tumor.

PMID- 15141061
TI  - To give or not to give? That is the question.

PMID- 15141062
TI  - Plant genetic resources and the law: past, present, and future.

PMID- 15141063
TI  - Coordinate expression and independent subcellular targeting of multiple proteins
      from a single transgene.
AB  - A variety of conventional methods allow the expression of multiple foreign
      proteins in plants by transgene stacking or pyramiding. However, most of these
      approaches have significant drawbacks. We describe a novel alternative, using a
      single transgene to coordinate expression of multiple proteins that are encoded
      as a polyprotein capable of dissociating into component proteins on translation.
      We demonstrate that this polyprotein system is compatible with the need to target
      proteins to a variety of subcellular locations, either cotranslationally or
      posttranslationally. It can also be used to coordinate the expression of
      selectable marker genes and effect genes or to link genes that are difficult to
      assay to reporter genes that are easily monitored. The unique features of this
      polyprotein system are based on the novel activity of the 2A peptide of Foot-and
      mouth disease virus (FMDV) that acts cotranslationally to effect a dissociation
      of the polyprotein while allowing translation to continue. This polyprotein
      system has many applications both as a research tool and for metabolic
      engineering and protein factory applications of plant biotechnology.

PMID- 15141064
TI  - High-throughput fluorescent tagging of full-length Arabidopsis gene products in
      planta.
AB  - We developed a high-throughput methodology, termed fluorescent tagging of full
      length proteins (FTFLP), to analyze expression patterns and subcellular
      localization of Arabidopsis gene products in planta. Determination of these
      parameters is a logical first step in functional characterization of the
      approximately one-third of all known Arabidopsis genes that encode novel proteins
      of unknown function. Our FTFLP-based approach offers two significant advantages:
      first, it produces internally-tagged full-length proteins that are likely to
      exhibit native intracellular localization, and second, it yields information
      about the tissue specificity of gene expression by the use of native promoters.
      To demonstrate how FTFLP may be used for characterization of the Arabidopsis
      proteome, we tagged a series of known proteins with diverse subcellular targeting
      patterns as well as several proteins with unknown function and unassigned
      subcellular localization.

PMID- 15141065
TI  - High-frequency transformation of undeveloped plastids in tobacco suspension
      cells.
AB  - Although leaf chloroplast transformation technology was developed more than a
      decade ago, no reports exist of stable transformation of undeveloped plastids or
      other specialized plastid types, such as proplastids, etioplasts, or amyloplasts.
      In this work we report development of a dark-grown tobacco suspension cell model
      system to investigate the transformation potential of undeveloped plastids.
      Electron microscope analysis confirmed that the suspension cells carry plastids
      that are significantly smaller (approximately 50-fold less in volume) and have a
      very different subcellular localization and developmental state than leaf cell
      chloroplasts. Using antibiotic selection in the light, we demonstrated that both
      plastid and nuclear transformation of these cell suspensions is efficient and
      reproducible, with plastid transformation frequency at least equal to that of
      leaf chloroplast transformation. Homoplasmic plastid transformants are readily
      obtained in cell colonies, or in regenerated plants, providing a more consistent
      and versatile model than the leaf transformation system. Because of the
      uniformity of the cell suspension model, we could further show that growth rate,
      selection scheme, particle size, and DNA amount influence the frequency of
      transformation. Our results indicate that the rate-limiting steps for nuclear and
      plastid transformation are different, and each must be optimized separately. The
      suspension cell system will be useful as a model for understanding transformation
      in those plant species that utilize dark-grown embryogenic cultures and for
      characterizing the steps that lead to homoplasmic plastid transformation.

PMID- 15141066
TI  - Proton-transfer-reaction mass spectrometry as a new tool for real time analysis
      of root-secreted volatile organic compounds in Arabidopsis.
AB  - Plant roots release about 5% to 20% of all photosynthetically-fixed carbon, and
      as a result create a carbon-rich environment for numerous rhizosphere organisms,
      including plant pathogens and symbiotic microbes. Although some characterization
      of root exudates has been achieved, especially of secondary metabolites and
      proteins, much less is known about volatile organic compounds (VOCs) released by
      roots. In this communication, we describe a novel approach to exploring these
      rhizosphere VOCs and their induction by biotic stresses. The VOC formation of
      Arabidopsis roots was analyzed using proton-transfer-reaction mass spectrometry
      (PTR-MS), a new technology that allows rapid and real time analysis of most
      biogenic VOCs without preconcentration or chromatography. Our studies revealed
      that the major VOCs released and identified by both PTR-MS and gas chromatography
      mass spectrometry were either simple metabolites, ethanol, acetaldehyde, acetic
      acid, ethyl acetate, 2-butanone, 2,3,-butanedione, and acetone, or the
      monoterpene, 1,8-cineole. Some VOCs were found to be produced constitutively
      regardless of the treatment; other VOCs were induced specifically as a result of
      different compatible and noncompatible interactions between microbes and insects
      and Arabidopsis roots. Compatible interactions of Pseudomonas syringae DC3000 and
      Diuraphis noxia with Arabidopsis roots resulted in the rapid release of 1,8
      cineole, a monoterpene that has not been previously reported in Arabidopsis.
      Mechanical injuries to Arabidopsis roots did not produce 1,8-cineole nor any C6
      wound-VOCs; compatible interactions between Arabidopsis roots and Diuraphis noxia
      did not produce any wound compounds. This suggests that Arabidopsis roots respond
      to wounding differently from above-ground plant organs. Trials with incompatible
      interactions did not reveal a set of compounds that was significantly different
      compared to the noninfected roots. The PTR-MS method may open the way for
      functional root VOC analysis that will complement genomic investigations in
      Arabidopsis.

PMID- 15141067
TI  - National Science Foundation-sponsored workshop report. Draft plan for soybean
      genomics.
AB  - Recent efforts to coordinate and define a research strategy for soybean (Glycine
      max) genomics began with the establishment of a Soybean Genetics Executive
      Committee, which will serve as a communication focal point between the soybean
      research community and granting agencies. Secondly, a workshop was held to define
      a strategy to incorporate existing tools into a framework for advancing soybean
      genomics research. This workshop identified and ranked research priorities
      essential to making more informed decisions as to how to proceed with large scale
      sequencing and other genomics efforts. Most critical among these was the need to
      finalize a physical map and to obtain a better understanding of genome
      microstructure. Addressing these research needs will require pilot work on new
      technologies to demonstrate an ability to discriminate between recently
      duplicated regions in the soybean genome and pilot projects to analyze an
      adequate amount of random genome sequence to identify and catalog common repeats.
      The development of additional markers, reverse genetics tools, and bioinformatics
      is also necessary. Successful implementation of these goals will require close
      coordination among various working groups.

PMID- 15141068
TI  - Gene-specific involvement of beta-oxidation in wound-activated responses in
      Arabidopsis.
AB  - The coordinated induced expression of beta-oxidation genes is essential to
      provide the energy supply for germination and postgerminative development.
      However, very little is known about other functions of beta-oxidation in
      nonreserve organs. We have identified a gene-specific pattern of induced beta
      oxidation gene expression in wounded leaves of Arabidopsis. Mechanical damage
      triggered the local and systemic induction of only ACX1 among acyl-coenzyme A
      oxidase (ACX) genes, and KAT2/PED1 among 3-ketoacyl-coenzyme A thiolase (KAT)
      genes in Arabidopsis. In turn, wounding induced KAT5/PKT2 only systemically.
      Although most of the beta-oxidation genes were activated by wound-related factors
      such as dehydration and abscisic acid, jasmonic acid (JA) induced only ACX1 and
      KAT5. Reduced expression of ACX1 or KAT2 genes, in transgenic plants expressing
      their corresponding mRNAs in antisense orientation, correlated with defective
      wound-activated synthesis of JA and with reduced expression of JA-responsive
      genes. Induced expression of JA-responsive genes by exogenous application of JA
      was unaffected in those transgenic plants, suggesting that ACX1 and KAT2 play a
      major role in driving wound-activated responses by participating in the
      biosynthesis of JA in wounded Arabidopsis plants.

PMID- 15141071
TI  - Calorie restriction Un-SIR-tainty.

PMID- 15141072
TI  - Slipshod survival.

PMID- 15141070
TI  - The dominant mutant Wavy auricle in blade1 disrupts patterning in a lateral
      domain of the maize leaf.
AB  - Mature maize leaves have defined cell types along the proximal distal and medial
      lateral axes. The patterning events that establish these axes take place early in
      leaf initiation. We have identified a new dominant mutation, Wavy auricle in
      blade1 (Wab1), which affects patterning in both axes in a dose-dependent manner.
      Wab1 leaves are narrower than normal leaves and displace proximal tissues
      distally. We show that the proximal distal patterning defects are not due to
      misexpression of knox genes. Genetic analyses suggest that the action of dominant
      Wab1 alleles is localized to a lateral domain of the leaf, located between the
      midvein and the marginal domain that is determined by narrow sheath function.
      Thus, Wab1 defines a knox-independent pathway that affects specification of the
      proximal distal axis of the maize leaf. We suggest that failure to elaborate a
      normal lateral domain in the Wab1 leaf is responsible for disrupting patterning
      of the proximal distal axis.

PMID- 15141069
TI  - Plasma membrane depolarization induced by abscisic acid in Arabidopsis suspension
      cells involves reduction of proton pumping in addition to anion channel
      activation, which are both Ca2+ dependent.
AB  - In Arabidopsis suspension cells a rapid plasma membrane depolarization is
      triggered by abscisic acid (ABA). Activation of anion channels was shown to be a
      component leading to this ABA-induced plasma membrane depolarization. Using
      experiments employing combined voltage clamping, continuous measurement of
      extracellular pH, we examined whether plasma membrane H(+)-ATPases could also be
      involved in the depolarization. We found that ABA causes simultaneously cell
      depolarization and medium alkalinization, the second effect being abolished when
      ABA is added in the presence of H+ pump inhibitors. Inhibition of the proton pump
      by ABA is thus a second component leading to the plasma membrane depolarization.
      The ABA-induced depolarization is therefore the result of two different
      processes: activation of anion channels and inhibition of H(+)-ATPases. These two
      processes are independent because impairing one did not suppress the
      depolarization. Both processes are however dependent on the [Ca2+]cyt increase
      induced by ABA since increase in [Ca(2+)](cyt) enhanced anion channels and
      impaired H(+)-ATPases.

PMID- 15141073
TI  - Learning is in the blood. Weakening the immune system saps brainpower.

PMID- 15141074
TI  - Vital connections.
AB  - Scientists are currently exploring the structure and behavior of complex
      biological systems, which consist of networks of interacting entities. A recent
      paper in Proceedings of the Royal Society of London Series B Biological Sciences
      describes the distinctive characteristics of aging-related proteins in the yeast
      protein-protein interaction network. In this Perspective, I discuss the
      implications of these findings for longevity research.

PMID- 15141075
TI  - The ageless question--what accounts for age-related cognitive decline?
AB  - Recent studies have provided partial insight into mechanisms underlying age
      related declines in brain function. However, precisely where in the brain these
      changes occur is not entirely clear. A new report suggests that the hippocampal
      dentate gyrus may be the earliest locus of age-related memory decline.

PMID- 15141076
TI  - The ribosome as an entropy trap.
AB  - To determine the effectiveness of the ribosome as a catalyst, we compared the
      rate of uncatalyzed peptide bond formation, by the reaction of the ethylene
      glycol ester of N-formylglycine with Tris(hydroxymethyl)aminomethane, with the
      rate of peptidyl transfer by the ribosome. Activation parameters were also
      determined for both reactions, from the temperature dependence of their second
      order rate constants. In contrast with most protein enzymes, the enthalpy of
      activation is slightly less favorable on the ribosome than in solution. The 2 x
      10(7)-fold rate enhancement produced by the ribosome is achieved entirely by
      lowering the entropy of activation. These results are consistent with the view
      that the ribosome enhances the rate of peptide bond formation mainly by
      positioning the substrates and/or water exclusion within the active site, rather
      than by conventional chemical catalysis.

PMID- 15141077
TI  - Microtesla MRI with a superconducting quantum interference device.
AB  - MRI scanners enable fast, noninvasive, and high-resolution imaging of organs and
      soft tissue. The images are reconstructed from NMR signals generated by nuclear
      spins that precess in a static magnetic field B0 in the presence of magnetic
      field gradients. Most clinical MRI scanners operate at a magnetic field B0 = 1.5
      T, corresponding to a proton resonance frequency of 64 MHz. Because these systems
      rely on large superconducting magnets, they are costly and demanding of
      infrastructure. On the other hand, low-field imagers have the potential to be
      less expensive, less confining, and more mobile. The major obstacle is the
      intrinsically low sensitivity of the low-field NMR experiment. Here, we show that
      prepolarization of the nuclear spins and detection with a superconducting quantum
      interference device (SQUID) yield a signal that is independent of B0, allowing
      acquisition of high-resolution MRIs in microtesla fields. Reduction of the
      strength of the measurement field eliminates inhomogeneous broadening of the NMR
      lines, resulting in enhanced signal-to-noise ratio and spatial resolution for a
      fixed strength of the magnetic field gradients used to encode the image. We
      present high-resolution images of phantoms and other samples and T1-weighted
      contrast images acquired in highly inhomogeneous magnetic fields of 132 microT;
      here, T1 is the spin-lattice relaxation time. These techniques could readily be
      adapted to existing multichannel SQUID systems used for magnetic source imaging
      of brain signals. Further potential applications include low-cost systems for
      tumor screening and imaging peripheral regions of the body.

PMID- 15141078
TI  - T cell deficiency leads to cognitive dysfunction: implications for therapeutic
      vaccination for schizophrenia and other psychiatric conditions.
AB  - The effects of the adaptive immune system on the cognitive performance and
      abnormal behaviors seen in mental disorders such as schizophrenia have never been
      documented. Here, we show that mice deprived of mature T cells manifested
      cognitive deficits and behavioral abnormalities, which were remediable by T cell
      restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a
      weak agonist of numerous self-reactive T cells), can overcome the behavioral and
      cognitive abnormalities that accompany neurotransmitter imbalance induced by
      (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that
      peripheral T cell deficit can lead to cognitive and behavioral impairment,
      highlight the importance of properly functioning adaptive immunity in the
      maintenance of mental activity and in coping with conditions leading to cognitive
      deficits. These findings point to critical factors likely to contribute to age-
      and AIDS-related dementias and might herald the development of a therapeutic
      vaccination for fighting off cognitive dysfunction and psychiatric conditions.

PMID- 15141079
TI  - Hypoxia induces adhesion molecules on cancer cells: A missing link between
      Warburg effect and induction of selectin-ligand carbohydrates.
AB  - Cancer cells undergo distinct metabolic changes to cope with their hypoxic
      environment. These changes are achieved at least partly by the action of
      transcriptional factors called hypoxia-inducible factors (HIFs). We investigated
      gene expression in cultured human colon cancer cells induced by hypoxic
      conditions with special reference to cell-adhesion molecules and carbohydrate
      determinants having cell-adhesive activity by using DNA-microarray and RT-PCR
      techniques. Hypoxic culture of colon cancer cells induced a marked increase in
      expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a
      determinants at the cell surface, which led to a definite increase in cancer cell
      adhesion to endothelial E-selectin. The transcription of genes for
      fucosyltransferase VII (FUT7), sialyltransferase ST3Gal-I (ST3O), and UDP
      galactose transporter-1 (UGT1), which are all known to be involved in the
      synthesis of the carbohydrate ligands for E-selectin, was significantly induced
      in cancer cells by hypoxic culture. In addition, a remarkable induction was
      detected in the genes for syndecan-4 (SDC4) and alpha5-integrin (ITGA5), the cell
      adhesion molecules involved in the enhanced adhesion of cancer cells to
      fibronectin. The transcriptional induction by hypoxia was reproduced in the
      luciferase-reporter assays for these genes, which were significantly suppressed
      by the co-transfection of a dominant-negative form of HIF. These results indicate
      that the metabolic shifts of cancer cells partly mediated by HIFs significantly
      enhance their adhesion to vascular endothelial cells, through both selectin- and
      integrin-mediated pathways, and suggest that this enhancement further facilitates
      hematogenous metastasis of cancers and tumor angiogenesis.

PMID- 15141080
TI  - Natural killer cells distinguish innocuous and destructive forms of pancreatic
      islet autoimmunity.
AB  - In both human patients and murine models, the progression from insulitis to
      diabetes is neither immediate nor inevitable, as illustrated by the innocuous
      versus destructive infiltrates of BDC2.5 transgenic mice on the nonobese diabetic
      (NOD) versus C57BL/6.H-2g7 genetic backgrounds. Natural killer (NK)-cell-specific
      transcripts and the proportion of NK cells were increased in leukocytes from the
      aggressive BDC2.5/B6.H-2g7 lesions. NK cell participation was also enhanced in
      the aggressive lesions provoked by CTLA-4 blockade in BDC2.5/NOD mice. In this
      context, depletion of NK cells significantly inhibited diabetes development. NOD
      and B6.H-2g7 mice exhibit extensive variation in NK receptor expression,
      reminiscent of analogous human molecules. NK cells can be important players in
      type 1 diabetes, a role that was previously underappreciated.

PMID- 15141081
TI  - Mechanical tweezer action by self-tightening knots in surfactant nanotubes.
AB  - Entanglements and trefoil knots on surfactant nanotubes in the liquid phase were
      produced by a combination of network self-organization and micromanipulation. The
      resulting knots are self-tightening, and the tightening is driven by minimization
      of surface free energy of the surfactant membrane material. The formation of the
      knot and the steady-state knot at quasi-equilibrium can be directly followed and
      localized by using fluorescence microscopy. Knots on nanotubes can be used as
      nanoscale mechanical tweezers for trapping and manipulation of single nano- and
      micrometer-sized high-aspect ratio objects. Furthermore, we demonstrate that by
      controlling the surface tension, objects captured by a knot can be transported
      along given trajectories defined by the nanotube axes.

PMID- 15141082
TI  - Oligomeric catechins: an enabling synthetic strategy by orthogonal activation and
      C(8) protection.
AB  - Controlled formation of oligomeric catechins has become possible by an orthogonal
      synthetic strategy. Bromo-capping of the C(8) position of the flavan skeleton
      enabled the equimolar coupling of electrophilic and nucleophilic catechin
      derivatives, enabling an efficient synthetic strategy to complex catechin
      oligomers.

PMID- 15141084
TI  - Stereocontrolled total synthesis of (+)-vincristine.
AB  - An efficient total synthesis of (+)-vincristine has been accomplished through a
      stereoselective coupling of demethylvindoline and the eleven-membered
      carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of
      17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with
      mixed anhydride method. Although an initial attempt of coupling by using
      demethylvindoline formamide was not successful and resulted in recovery of the
      starting compounds, the reaction using demethylvindoline took place smoothly to
      furnish the desired bisindole product with the correct stereochemistry at C18'.
      After formation of the piperidine ring by sequential removal of the protective
      groups and intramolecular nucleophilic cyclization, the total synthesis of
      vincristine was completed by formylation of N1.

PMID- 15141083
TI  - Synthetic studies of roquefortine C: synthesis of isoroquefortine C and a
      heterocycle.
AB  - The syntheses of isoroquefortine C and a related heterocycle were achieved by
      implementation of both intra- and intermolecular vinyl amidation reactions. These
      accomplishments represent a significant advance in the use of these strategies in
      the generation of complex molecules.

PMID- 15141085
TI  - Catalysis-based enantioselective total synthesis of the macrocyclic spermidine
      alkaloid isooncinotine.
AB  - A concise and efficient total synthesis of the spermidine alkaloid (-)
      isooncinotine (1) incorporating a 22-membered lactam ring is outlined. The
      approach is largely catalysis-based, involving a selective iron-catalyzed alkyl
      aryl cross-coupling reaction of a difunctionalized pyridine substrate, a
      heterogeneous asymmetric hydrogenation step to set the chiral center of the
      target, and a highly integrated ring-closing metathesis/hydrogenation sequence to
      forge the saturated macrocyclic edifice in a single operation.

PMID- 15141087
TI  - Genetic variation in cancer predisposition: mutational decay of a robust genetic
      control network.
AB  - A computational model of cancer progression is used to study how mutations in
      genes that control tumor initiation and progression accumulate in populations.
      The model assumes that cancer occurs only after a cell lineage has progressed
      through a series of stages. The greater the number of stages, the more strongly
      the individual is protected against cancer. It is shown that an extra stage
      initially improves the survival of individuals by decreasing mortality from
      cancer. However, the additional buffering by an extra stage reduces the impact of
      any single hereditary mutation and therefore allows the accumulation of more
      nonlethal mutations in the population. Extra stages thereby lead to the evolution
      of partially decreased cancer mortality and significantly increased genetic
      predisposition to disease in the population as a whole. In general, the model
      illustrates how all robust control networks allow the accumulation of deleterious
      mutations. An increase in the number of buffering components leads to significant
      mutational decay in the protection provided by each buffering component and
      increased genetic predisposition to disease. An extra buffering component's net
      contribution to survival and reproduction is often small.

PMID- 15141086
TI  - Measurements of age-related changes of physiological processes that predict
      lifespan of Caenorhabditis elegans.
AB  - Aging is characterized by progressive, degenerative changes in many tissues. To
      elucidate the relationships among degenerative changes in Caenorhabditis elegans,
      we developed methods to measure age-related changes quantitatively and analyzed
      correlations among these changes by using a longitudinal study. The age-related
      declines of pharyngeal pumping and body movement were positively correlated with
      each other and lifespan. These findings suggest that the declines of pharyngeal
      pumping and body movement cause a decline in survival probability or that a
      shared regulatory system mediates the declines in pharyngeal pumping, body
      movement, and survival probability. Furthermore, measurements of these processes
      can be used to predict lifespan and detect premature aging. The declines of
      physiological processes were measured in daf-2, age-1, daf-16, eat-2, and clk-1
      mutants that have altered lifespans. Each mutant strain displayed changes in one
      or more age-related declines, but the correlations among age-related changes were
      similar to WT. These measurements were used to generate a system of four stages
      that describes the aging process and is useful for the analysis of genetic and
      environmental effects on aging.

PMID- 15141088
TI  - Rescuing cystic fibrosis transmembrane conductance regulator (CFTR)-processing
      mutants by transcomplementation.
AB  - Most cases of cystic fibrosis (CF) are caused by mutations that block the
      biosynthetic maturation of the CF gene product, the CF transmembrane conductance
      regulator (CFTR) chloride channel. CFTR-processing mutants fail to escape the
      endoplasmic reticulum and are rapidly degraded. Current efforts to induce the
      maturation of CFTR mutants target components of the biosynthetic pathway (e.g.,
      chaperones) rather than CFTR per se. Such methods are inherently nonspecific.
      Here we show that the most common CF-causing mutant (DeltaF508-CFTR) can form
      mature, functional chloride channels that reach the cell surface when coexpressed
      with several other CFTR-processing mutants or with amino fragments of the wild
      type CFTR protein. This transcomplementation effect required a specific match
      between the region flanking the disease-causing mutation and the complementing
      fragment; e.g., amino fragments complemented DeltaF508-CFTR but not H1085R (a
      carboxy-processing mutant), whereas a carboxy fragment complemented H1085R but
      not DeltaF508-CFTR. Transcomplementing fragments did not affect CFTR interactions
      with Hsc70, a chaperone previously implicated in CFTR biosynthesis. Instead, they
      may promote CFTR maturation by blocking nonproductive interactions between
      domains within the same or neighboring CFTR polypeptides that prevent normal
      processing. These findings indicate that it may be possible to develop CF
      therapies (e.g., mini-cDNA constructs for gene therapy) that are tailored to
      specific disease-causing mutants of CFTR.

PMID- 15141089
TI  - Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a
      mechanism for stabilizing bicarbonate transport.
AB  - The acid- and volume-sensitive TASK2 K+ channel is strongly expressed in renal
      proximal tubules and papillary collecting ducts. This study was aimed at
      investigating the role of TASK2 in renal bicarbonate reabsorption by using the
      task2 -/- mouse as a model. After backcross to C57BL6, task2 -/- mice showed an
      increased perinatal mortality and, in adulthood, a reduced body weight and
      arterial blood pressure. Patch-clamp experiments on proximal tubular cells
      indicated that TASK2 was activated during HCO3- transport. In control inulin
      clearance measurements, task2 -/- mice showed normal NaCl and water excretion.
      During i.v. NaHCO3 perfusion, however, renal Na+ and water reabsorption capacity
      was reduced in -/- animals. In conscious task2 -/- mice, blood pH, HCO3-
      concentration, and systemic base excess were reduced but urinary pH and HCO3-
      were increased. These data suggest that task2 -/- mice exhibit metabolic acidosis
      caused by renal loss of HCO3-. Both in vitro and in vivo results demonstrate the
      specific coupling of TASK2 activity to HCO3- transport through external
      alkalinization. The consequences of the task2 gene inactivation in mice are
      reminiscent of the clinical manifestations seen in human proximal renal tubular
      acidosis syndrome.

PMID- 15141090
TI  - Establishment of a normal medakafish spermatogonial cell line capable of sperm
      production in vitro.
AB  - Spermatogonia are the male germ stem cells that continuously produce sperm for
      the next generation. Spermatogenesis is a complicated process that proceeds
      through mitotic phase of stem cell renewal and differentiation, meiotic phase,
      and postmeiotic phase of spermiogenesis. Full recapitulation of spermatogenesis
      in vitro has been impossible, as generation of normal spermatogonial stem cell
      lines without immortalization and production of motile sperm from these cells
      after long-term culture have not been achieved. Here we report the derivation of
      a normal spermatogonial cell line from a mature medakafish testis without
      immortalization. After 140 passages during 2 years of culture, this cell line
      retains stable but growth factor-dependent proliferation, a diploid karyotype,
      and the phenotype and gene expression pattern of spermatogonial stem cells.
      Furthermore, we show that this cell line can undergo meiosis and spermiogenesis
      to generate motile sperm. Therefore, the ability of continuous proliferation and
      sperm production in culture is an intrinsic property of medaka spermatogonial
      stem cells, and immortalization apparently is not necessary to derive male germ
      cell cultures. Our findings and cell line will offer a unique opportunity to
      study and recapitulate spermatogenesis in vitro and to develop approaches for
      germ-line transmission.

PMID- 15141091
TI  - SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA
      complexes.
AB  - Urinary tract malformations constitute the most frequent cause of chronic renal
      failure in the first two decades of life. Branchio-otic (BO) syndrome is an
      autosomal dominant developmental disorder characterized by hearing loss. In
      branchio-oto-renal (BOR) syndrome, malformations of the kidney or urinary tract
      are associated. Haploinsufficiency for the human gene EYA1, a homologue of the
      Drosophila gene eyes absent (eya), causes BOR and BO syndromes. We recently
      mapped a locus for BOR/BO syndrome (BOS3) to human chromosome 14q23.1. Within the
      33-megabase critical genetic interval, we located the SIX1, SIX4, and SIX6 genes,
      which act within a genetic network of EYA and PAX genes to regulate
      organogenesis. These genes, therefore, represented excellent candidate genes for
      BOS3. By direct sequencing of exons, we identified three different SIX1 mutations
      in four BOR/BO kindreds, thus identifying SIX1 as a gene causing BOR and BO
      syndromes. To elucidate how these mutations cause disease, we analyzed the
      functional role of these SIX1 mutations with respect to protein-protein and
      protein-DNA interactions. We demonstrate that all three mutations are crucial for
      Eya1-Six1 interaction, and the two mutations within the homeodomain region are
      essential for specific Six1-DNA binding. Identification of SIX1 mutations as
      causing BOR/BO offers insights into the molecular basis of otic and renal
      developmental diseases in humans.

PMID- 15141092
TI  - Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive
      oxygen species-dependent and -independent components of aging.
AB  - Aging is thought to be caused by the accumulation of damage, primarily from
      oxidative modifications of cellular components by reactive oxygen species (ROS).
      Here we used yeast methionine sulfoxide reductases MsrA and MsrB to address this
      hypothesis. In the presence of oxygen, these antioxidants could increase yeast
      lifespan and did so independent of the lifespan extension offered by caloric
      restriction. However, under ROS-deficient, strictly anaerobic conditions, yeast
      lifespan was shorter, not affected by MsrA or MsrB, and further reduced by
      caloric restriction. In addition, we identified changes in the global gene
      expression associated with aging in yeast, and they did not include oxidative
      stress genes. Our findings suggest how the interplay between ROS, antioxidants,
      and efficiency of energy production regulates the lifespan. The data also suggest
      a model wherein factors implicated in aging (for example, ROS) may influence the
      lifespan yet not be the cause of aging.

PMID- 15141093
TI  - Leptin modulates beta cell expression of IL-1 receptor antagonist and release of
      IL-1beta in human islets.
AB  - High concentrations of glucose induce beta cell production of IL-1beta, leading
      to impaired beta cell function and apoptosis in human pancreatic islets. IL-1
      receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1beta and
      protects cultured human islets from glucotoxicity. Therefore, the balance of IL
      1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes. In the
      present study, we observed expression of IL-1Ra in human pancreatic beta cells of
      nondiabetic individuals, which was decreased in tissue sections of type 2
      diabetic patients. In vitro, chronic exposure of human islets to leptin, a
      hormone secreted by adipocytes, decreased beta cell production of IL-1Ra and
      induced IL-1beta release from the islet preparation, leading to impaired beta
      cell function, caspase-3 activation, and apoptosis. Exogenous addition of IL-1Ra
      protected cultured human islets from the deleterious effects of leptin.
      Antagonizing IL-1Ra by introduction of small interfering RNA to IL-1Ra into human
      islets led to caspase-3 activation, DNA fragmentation, and impaired beta cell
      function. Moreover, siIL-1Ra enhanced glucose-induced beta cell apoptosis. These
      findings demonstrate expression of IL-1Ra in the human beta cell, providing
      localized protection against leptin- and glucose-induced islet IL-1beta.

PMID- 15141094
TI  - The effect of ethylene exposure on ethylene oxide in blood and on hepatic
      cytochrome p450 in Fischer rats.
AB  - Ethylene (74-85-1) is an important petrochemical and is produced endogenously. It
      is metabolized to ethylene oxide (EO) by cytochrome P450. We studied the
      inhibition of cytochrome P450 activity during exposure to ethylene, and verified
      that this inhibition was reflected in the concentration of EO in the blood. Male
      F344 rats were exposed to 1000, 600, and 300 ppm ethylene by nose-only inhalation
      for up to 6 h. Blood samples were obtained during exposure. On exposure to 600
      ppm ethylene, blood EO concentration increased during the first hour of exposure
      and then decreased to approximately half of the peak blood concentration. A less
      pronounced decrease was observed at 300 ppm, and at 1000 ppm little change was
      observed between 10 min and 6 h of exposure. For the analysis of cytochrome P450
      and isozyme-specific substrate activities, groups of four male F344 rats were
      removed for the collection of liver at various times after exposure to 300, 600,
      or 1000 ppm ethylene. At all concentrations, liver microsomal cytochrome P450
      decreased during exposure. Of the various monooxygenase activities measured, 4
      nitrophenol hydroxylase was the one most consistently altered, with maximal
      inhibition (approximately 50%) at 2 h of exposure to 1000 ppm ethylene, 4 h at
      600 ppm, and 6 h at 300 ppm. Activity recovered to control levels by 6 h after
      exposure. Cytochrome P450 2E1 appears to be the major isoform of cytochrome P450
      inhibited by exposure to ethylene, and this may explain in part the observed
      alteration in EO blood kinetics.

PMID- 15141095
TI  - Dose-dependent alterations in gene expression and testosterone synthesis in the
      fetal testes of male rats exposed to di (n-butyl) phthalate.
AB  - Exposure to di (n-butyl) phthalate (DBP) in utero impairs the development of the
      male rat reproductive tract. The adverse effects are due in part to a coordinated
      decrease in expression of genes involved in cholesterol transport and
      steroidogenesis with a resultant reduction in testosterone production in the
      fetal testis. To determine the dose-response relationship for the effect of DBP
      on steroidogenesis in fetal rat testes, pregnant Sprague-Dawley rats received
      corn oil (vehicle control) or DBP (0.1, 1.0, 10, 50, 100, or 500 mg/kg/day) by
      gavage daily from gestation day (GD) 12 to 19. Testes were isolated on GD 19, and
      changes in gene and protein expression were quantified by RT-PCR and Western
      analysis. Fetal testicular testosterone concentration was determined by
      radioimmunoassay. DBP exposure resulted in significant dose-dependent reductions
      in mRNA and protein concentration of scavenger receptor, steroidogenic acute
      regulatory protein (StAR), cytochrome P450 side-chain cleavage, 3beta
      hydroxysteroid dehydrogenase, and cytochrome P450c17. Testicular testosterone was
      reduced at doses of 50 mg/kg/day and above. Whole-testis expression of peripheral
      benzodiazepine receptor (PBR) mRNA, which functions with StAR to transport
      cholesterol across the mitochondrial membrane, was upregulated following exposure
      to DBP at 500 mg/kg/day. By immunocytochemistry, however, PBR protein was reduced
      in interstitial cells and also expressed but not reduced in gonocytes. Our
      results demonstrate a coordinate, dose-dependent reduction in the expression of
      key genes and proteins involved in cholesterol transport and steroidogenesis and
      a corresponding reduction in testosterone in fetal testes following maternal
      exposure to DBP, at dose levels below which adverse effects are detected in the
      developing male reproductive tract. Alterations in gene and protein expression
      and testosterone synthesis may serve as sensitive indicators of testicular
      response to DBP.

PMID- 15141096
TI  - Intrathecal ketorolac in dogs and rats.
AB  - This study was conducted to assess spinal safety of the cyclo-oxygenase inhibitor
      ketorolac in dogs and rats. Beagle dogs were prepared with lumbar intrathecal
      catheters and received continuous spinal infusions of 5 mg/ml ketorolac (N = 6),
      0.5 mg/ml ketorolac (N = 8), or saline vehicle (N = 6) at 50 microl/h (1.2
      ml/day) for 28 days. No systematic drug or dose-related changes were observed in
      motor function, heart rate, or blood pressure. Histological examination revealed
      a mild pericatheter reaction in all groups with no drug or dose related effect
      upon spinal pathology at the lumbar site of highest drug concentration. Cisternal
      CSF protein was elevated for all treatment groups at necropsy, and cisternal
      glucose was within normal range for all treatment groups, though three dogs
      displayed decreases in cisternal glucose. Significant reductions in hematocrit
      were noted, and increased incidence of gastric bleeding at necropsy was observed
      in animals receiving ketorolac. Intrathecal ketorolac kinetics revealed a
      biphasic clearance: t1/2 s = 10.3 and 53 min, respectively. After initiation of
      infusion (0.5 mg and 5 mg/ml/50 microl/h), lumbar CSF concentrations of ketorolac
      were 3.8 and 52.7 microg/ml, respectively. Bolus and continuous infusion of
      intrathecal ketorolac resulted in significant reduction of lumbar CSF PGE2
      concentrations. In rats, with intrathecal catheters, four daily bolus deliveries
      of saline or ketorolac (5 mg/ml/10 microl) had no effect upon spinal histology or
      upon spinal cord blood flow. These data indicate that intrathecal ketorolac in
      two species at the dose/concentrations employed does not induce evident spinal
      pathology but diminishes spinal prostaglandin release.

PMID- 15141097
TI  - Human carcinogenic risk evaluation, Part III: Assessing cancer hazard and risk in
      human drug development.
AB  - Assessing cancer risk for human pharmaceuticals is important because drugs are
      taken at pharmacologically active doses and often on a chronic basis.
      Epidemiologic studies on patient populations have limited value because of the
      long latency period for most cancers and because these studies lack sensitivity.
      The Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug
      Administration relies on short-term surrogate assays (genetic toxicology studies)
      to assess risk to patients involved in clinical trials and on rodent
      carcinogenicity studies to assess cancer risk for drug approval. Unlike some
      other agencies that typically perform quantitative risk assessments on chemical
      pollutants or pesticide products, CDER does not perform such quantitative
      extrapolations. Rather, the evaluation of risk is the result of an integrated
      assessment of what is known about the drug, and risk is considered in the context
      of the clinical benefit. Mode of action of carcinogenesis and thresholds for
      effects are important considerations. The results of carcinogenicity studies of
      approved products are published in the drug labeling and individual clinicians
      balance risk and benefit in making prescribing decisions.

PMID- 15141098
TI  - Erk1/2 phosphorylation and reactive oxygen species formation via nitric oxide and
      Akt-1/Raf-1 crosstalk in cultured rat cerebellar granule cells exposed to the
      organic solvent 1,2,4-trimethylcyclohexane.
AB  - Previously, we have shown that exposure of cultured rat cerebellar granule cells
      to the hydrocarbon solvent 1,2,4-trimethylcyclohexane leads to formation of
      reactive oxygen species (ROS). However, the cellular mechanisms responsible for
      formation of ROS in these cells after exposure to organic solvents are poorly
      understood. Here, we found that 1,2,4-trimethylcyclohexane induced a time and
      concentration dependent dephosphorylation of Akt-1 at Ser-473 and Raf-1 at Ser
      259. An increased level of phosphorylated extracellular signal-regulated kinases
      (Erk1/2) at Tyr-204 was observed. By use of the nitric oxide synthase inhibitors
      N(omega)-nitro-L-arginine methylester and diphenyleneiodonium, we found that
      intracellular formation of nitric oxide was necessary for phosphorylation of
      Erk1/2 and for the formation of ROS. Furthermore, the ROS formation was inhibited
      by the Erk1/2 pathway inhibitor U0126. A 1,2,4-trimethylcyclohexane (TMCH)
      induced cell death was lowered by U0126 and the free radical scavenger vitamin E.
      Our results show that Erk1/2 kinases and nitric oxide (NO) may participate in ROS
      formation induced by 1,2,4-trimethylcyclohexane in cultured rat cerebellar
      granule cells, and also indicate a crosstalk between Akt and the Raf-Mek-Erk
      signaling systems.

PMID- 15141099
TI  - Environmental boron exposure and activity of delta-aminolevulinic acid
      dehydratase (ALA-D) in a newborn population.
AB  - Following boron intake, multiple effects have been observed in animal
      experiments. However, human data is lacking, and no data is available on the
      ability of boron to accumulate in fetal tissues. Positive responses in animal
      species suggest that developmental toxicity may be an area of concern in humans,
      following exposure to boron. Two hypotheses have seemed to account for the
      multiple effects described in scientific findings. One hypothesis is that boron
      is a negative regulator that influences a number of metabolic pathways by
      competitively inhibiting some key enzyme reactions. The other hypothesis is that
      boron has a role in ionic membrane transport regulations. To better understand
      boron potential toxicity, the present study examined the relationship between
      boron exposure and some key enzymes, well-known for their affinity for mineral
      elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two
      fundamental enzymes having a role in ionic membrane transport regulations (Ca
      pump and Na(+)K(+)-ATPase). We investigated the potential effects of an
      environmental boron exposure on the activity of these enzymes in an urban
      population of 197 "normal" newborns. Environmental boron exposure was assessed in
      placental tissue. Because of the well-known inhibiting effect of lead on these
      enzymes, cord blood and placental lead were also analyzed. After adjustment for
      potential confounders, including lead, placental boron levels were negatively
      significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase
      activities did not seem to be affected by the level of boron exposure. Given
      boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest
      that such a mechanism would explain the inhibiting effect of boron on ALA-D.

PMID- 15141100
TI  - The role of chromatin in molecular mechanisms of toxicity.
AB  - Eukaryotic cells store their genetic information in the form of a highly
      organized nucleoprotein complex termed chromatin. The high degree of compaction
      of DNA within chromatin places severe constraints on proteins that require access
      to the DNA template to facilitate gene transcription, DNA replication, and DNA
      repair. As a consequence, eukaryotic cells have developed sophisticated
      mechanisms to allow chromatin to be rapidly decompacted locally for access by DNA
      binding proteins. Once thought to play only a structural role, it now appears
      that chromatin plays a key regulatory role by marshalling access to the DNA
      template. We have reviewed the role played by chromatin in the cellular response
      to physiological and toxicological stimuli and described how changes in chromatin
      structure may in the future be used as markers of toxicity. We also review the
      evidence that chromatin itself is the direct target of certain toxicants and that
      toxicant-induced perturbations in chromatin structure may precipitate adverse
      effects.

PMID- 15141101
TI  - Comparison of chlorpyrifos-oxon and paraoxon acetylcholinesterase inhibition
      dynamics: potential role of a peripheral binding site.
AB  - The primary mechanism of action for organophosphorus (OP) insecticides, like
      chlorpyrifos and parathion, is to inhibit acetylcholinesterase (AChE) by their
      oxygenated metabolites (oxons), due to the phosphorylation of the serine hydroxyl
      group located in the active site of the molecule. The rate of phosphorylation is
      described by the bimolecular inhibitory rate constant (k(i)), which has been used
      for quantification of OP inhibitory capacity. It has been proposed that a
      peripheral binding site exists on the AChE molecule, which, when occupied,
      reduces the capacity of additional oxon molecules to phosphorylate the active
      site. The aim of this study was to evaluate the interaction of chlorpyrifos oxon
      (CPO) and paraoxon (PO) with rat brain AChE to assess the dynamics of AChE
      inhibition and the potential role of a peripheral binding site. The k(i) values
      for AChE inhibition determined at oxon concentrations of 1-100 nM were 0.206 +/-
      0.018 and 0.0216 nM(-1)h(-1) for CPO and PO, respectively. The spontaneous
      reactivation rates of the inhibited AChE for CPO and PO were 0.084-0.087 (two
      determinations) and 0.091 +/- 0.023 h(-1), respectively. In contrast, the k(i)
      values estimated at a low oxon concentration (1 pM) were approximately 1,000- and
      10,000-fold higher than those determined at high CPO and PO concentrations,
      respectively. At low concentrations, the k(i) estimates were approximately
      similar for both CPO and PO (150-180 [two determinations] and 300 +/- 180 nM(
      1)h(-1), respectively). This implies that, at low concentrations, both oxons
      exhibited similar inhibitory potency in contrast to the marked difference
      exhibited at higher concentrations. These results support the potential
      importance of a secondary peripheral binding site associated with AChE kinetics,
      particularly at low, environmentally relevant concentrations.

PMID- 15141102
TI  - Metabolic detoxification determines species differences in coumarin-induced
      hepatotoxicity.
AB  - Hepatotoxicity of coumarin is attributed to metabolic activation to an epoxide
      intermediate, coumarin 3,4-epoxide (CE). However, whereas rats are most
      susceptible to coumarin-induced hepatotoxicity, formation of CE is greatest in
      mouse liver microsomes, a species showing little evidence of hepatotoxicity.
      Therefore, the present work was designed to test the hypothesis that
      detoxification of CE is a major determinant of coumarin hepatotoxicity. CE can
      either rearrange spontaneously to o-hydroxyphenylacetaldehyde (o-HPA) or be
      conjugated with gluatathione (GSH). o-HPA is hepatotoxic and is further
      detoxified by oxidation to o-hydroxyphenylacetic acid (o-HPAA). In vitro
      experiments were conducted using mouse liver microsomes to generate a constant
      amount of CE, and cytosols from F344 rats, B6C3F1 mice, and human liver were used
      to characterize CE detoxification. All metabolites were quantified by HPLC
      methods with UV detection. In rats and mice, GSH conjugation occurred non
      enzymatically and through glutathione-S-transferases (GSTs), and the kinetics of
      GSH conjugation were similar in rats and mice. In rat liver cytosol, oxidation of
      o-HPA to o-HPAA was characterized with a high affinity K(m) of approximately 12
      microM, and a V(max) of approximately 1.5 nmol/min/mg protein. In contrast, the
      K(m) and V(max) for o-HPA oxidation in mouse liver cytosol were approximately 1.7
      microM and 5 nmol/min/mg protein, respectively, yielding a total intrinsic
      clearance through oxidation to o-HPAA that was 20 times higher in mouse than in
      rats. Human cytosols (two separate pools) detoxified CE through o-HPA oxidation
      with an apparent K(m) of 0.84 microM and a V(max) of 5.7 nmol/min/mg protein, for
      a net intrinsic clearance that was more than 50 times higher than the rat. All
      species also reduced o-HPA to o-hydroxyphenylethanol (o-HPE), but this was only a
      major reaction in rats. In the presence of a metabolic reaction replete with all
      necessary cofactors, GSH conjugation accounted for nearly half of all CE
      metabolites in rat and mouse, whereas the GSH conjugate represented only 10% of
      the metabolites in human cytosol. In mouse, o-HPAA represented the major ring
      opened metabolite, accounting for the remaining 50% of metabolites, and in human
      cytosol, o-HPAA was the major metabolite, representing nearly 90% of all CE
      metabolites. In contrast, no o-HPAA was detected in rats, whereas o-HPE
      represented a major metabolite. Collectively, these in vitro data implicate o-HPA
      detoxification through oxidation to o-HPAA as the major determinant of species
      differences in coumarin-induced hepatotoxicity.

PMID- 15141103
TI  - Cardiac effects of carbon monoxide and ambient particles in a rat model of
      myocardial infarction.
AB  - Ambient air pollution is a complex mixture of particulate matter (PM) and gaseous
      pollutants such as carbon monoxide (CO). The effect of exposure to CO, alone or
      in combination with ambient PM, on arrhythmia incidence is unclear. To evaluate
      these effects, left-ventricular myocardial infarction was induced in Sprague
      Dawley rats by thermocoagulation. Diazepam-sedated rats were exposed (1 h) to
      either filtered air (n = 40), CO (35 ppm, n = 19), concentrated air particles
      (CAPs, median concentration = 350.5 microg/m(3), n = 53), or CAPs and CO (CAPs
      median concentration = 318.2 microg/m(3), n = 23), 12-18 h after surgery. Each
      exposure was immediately preceded and followed by a 1 h exposure to filtered air
      (pre-exposure and post-exposure periods, respectively). The CO target dose of 35
      ppm is related to the 1 h U.S. National Ambient Air Quality Standard. Surface
      electrocardiograms were recorded and heart rate and arrhythmia incidence were
      quantified. CO exposure reduced ventricular premature beat (VPB) frequency by
      60.4% (p = 0.012) during the exposure period compared to controls. This effect
      was modified by both infarct type and the number of pre-exposure VPBs, and was
      not mediated through changes in heart rate. Overall, CAPs exposure increased VPB
      frequency during the exposure period, but this effect did not reach statistical
      significance. This effect was modified by the number of pre-exposure VPBs.
      Overall, neither CAPs nor CO had any effect on heart rate, but CAPs increased
      heart rate in specific subgroups. No significant interactions were observed
      between the effects of CO and CAPs. In this animal model, the responses to CO and
      CAPs are distinctly different.

PMID- 15141105
TI  - The marine toxin dinophysistoxin-2 induces differential apoptotic death of rat
      cerebellar neurons and astrocytes.
AB  - Diarrhetic shellfish poisoning (DSP) toxins of algal origin are frequent
      contaminants of coastal waters and seafood. The potential risk for human health
      due to the continuous presence of these toxins in food has not been clearly
      established. We have used cerebellar primary cultures to investigate the effects
      of the DSP toxin dinophysistoxin-2 (DTX-2) on central nervous system neurons and
      glial cells. Exposure to DTX-2 produced neurotoxicity at concentrations starting
      at 2.5 nM, characterized first by disintegration of neurites and later by cell
      death. DTX-2-induced neurodegeneration required long exposures (at least 20 h),
      involved DNA fragmentation and condensation and fragmentation of chromatin,
      typical hallmarks of apoptosis, and required the synthesis of new proteins. The
      concentration that reduced by 50% the maximum neuronal survival after 24 h
      exposure to DTX-2 (EC50(24)) was approximately 8 nM. Morphology and viability of
      glial cells remained unaffected up to at least 15 nM DTX-2. Higher concentrations
      of the toxin caused strong shrinkage of glial cell bodies and retraction of
      processes, and a significant reduction of glial cell viability. Glial toxicity by
      DTX-2 involved typical apoptotic condensation and fragmentation of chromatin.
      Compared to neurons, the effect on glial cells was a much shorter process, and
      extensive glial degeneration and death occurred after 7 h exposure to DTX-2
      (EC50(7) approximately 50 nM; EC50(24) approximately 30 nM). Although further
      experiments are needed to confirm these toxic actions in vivo, our in vitro data
      suggest that chronic exposure to amounts of DSP toxins below the current safety
      regulatory limits may represent a risk for human health that should be taken into
      consideration.

PMID- 15141104
TI  - 2,5-hexanedione and carbendazim coexposure synergistically disrupts rat
      spermatogenesis despite opposing molecular effects on microtubules.
AB  - 2,5-Hexanedione (2,5-HD), a taxol-like promoter of microtubule assembly, and
      carbendazim (CBZ), a colchicine-like inhibitor of microtubule assembly, are two
      environmental testicular toxicants that target and disrupt microtubule function
      in Sertoli cells. At the molecular level, these two toxicants have opposite
      effects on microtubule assembly, yet they share the common physiologic effect of
      inhibiting microtubule-dependent functions of Sertoli cells. By studying a
      combined exposure to 2,5-HD and CBZ, we sought to determine whether CBZ would
      antagonize or exacerbate the effects of an initial 2,5-HD exposure. In vitro, 2,5
      HD-treated tubulin had a decreased lag time and an increased maximal velocity of
      microtubule assembly. These 2,5-HD-induced in vitro alterations in microtubule
      assembly were normalized by CBZ exposure. In vivo, adult male rats were exposed
      to a 1% solution of 2,5-HD in the drinking water for 2.5 weeks. CBZ was
      administered by gavage (200 mg/kg body weight) at the same time as unilateral
      surgical ligation of the efferent ducts, 24 h before evaluation of the testis.
      Measures of testicular effect (testis weight, histopathologic changes [sloughing
      and vacuolization], and seminiferous tubule diameters) were all significantly
      altered with combined exposure. The testicular effects in the combined exposure
      group were either different (seminiferous tubule diameters), additive (%
      vacuolization), or greater than additive (% sloughing) compared to the effects of
      the individual toxicant exposure groups referenced to the controls. Therefore,
      CBZ coexposure does not antagonize the effects of an initial 2,5-HD exposure, as
      might be expected if their molecular effects on microtubule assembly were solely
      responsible for their combined toxicity; instead, 2,5-HD and CBZ act together to
      exacerbate the testicular injury.

PMID- 15141106
TI  - Chronic exposure to dibromoacetic acid, a water disinfection byproduct,
      diminishes primordial follicle populations in the rabbit.
AB  - To determine if dibromoacetic acid (DBA) affects ovarian folliculogenesis, four
      groups of female Dutch-belted rabbits were exposed daily to 0, 1, 5, or 50 mg
      DBA/kg body weight in drinking water beginning in utero from gestation day 15
      throughout life. Functionality of the endocrine axis was assessed by measuring
      serum concentrations of gonadotropins following an im injection of 10 microg GnRH
      at 12 (prepubertal; n = 6/dose group) and 24 (postpubertal; n = 10/dose group)
      weeks of age. A day after GnRH challenge, number of ovulation sites and ovarian
      weights were determined at necropsy. Left ovaries were processed for
      histopathology, serially sectioned at 6 microm, and every twelfth section stained
      with hematoxylin and eosin was evaluated. All healthy follicles were categorized
      as primordial, primary, small preantral, large preantral, or small antral
      follicles. The area of each section evaluated was measured and the number of
      follicles in each category expressed per mm2 unit area. In prepubertal animals,
      DBA caused a reduction in number of primordial follicles (p < 0.05) and total
      healthy follicles (p < 0.05) at 50 mg/kg dose level. In adult animals, there were
      fewer primordial follicles in both the 5 (p < 0.01) and 50 (p = 0.1) mg/kg dose
      groups. No profound changes in gonadotropin profiles were observed. Although
      chronic exposure to DBA did not appear to have an effect on late follicular
      development or ovulation, DBA did reduce the population of primordial follicles.
      The long-term health consequences of diminished primordial follicles are unknown,
      but it is very likely that reproductive senescence would occur earlier.

PMID- 15141108
TI  - Molecular similarity measures.
AB  - Molecular similarity is a pervasive concept in chemistry. It is essential to many
      aspects of chemical reasoning and analysis and is perhaps the fundamental
      assumption underlying medicinal chemistry. Dissimilarity, the complement of
      similarity, also plays a major role in a growing number of applications of
      molecular diversity in combinatorial chemistry, high-throughput screening, and
      related fields. How molecular information is represented, called the
      representation problem, is important to the type of molecular similarity analysis
      (MSA) that can be carried out in any given situation. In this work, four types of
      mathematical structure are used to represent molecular information: sets, graphs,
      vectors, and functions. Molecular similarity is a pairwise relationship that
      induces structure into sets of molecules, giving rise to the concept of a
      chemistry space. Although all three concepts molecular similarity, molecular
      representation, and chemistry space are treated in this chapter, the emphasis is
      on molecular similarity measures. Similarity measures, also called similarity
      coefficients or indices, are functions that map pairs of compatible molecular
      representations, that is, representations of the same mathematical form, into
      real numbers usually, but not always, lying on the unit interval. This chapter
      presents a somewhat pedagogical discussion of many types of molecular similarity
      measures, their strengths and limitations, and their relationship to one another.

PMID- 15141107
TI  - Acute exposure to methylmercury causes Ca2+ dysregulation and neuronal death in
      rat cerebellar granule cells through an M3 muscarinic receptor-linked pathway.
AB  - Acute exposure to low concentrations of methylmercury (MeHg) causes a severe loss
      of intracellular calcium (Ca2+(i)) homeostasis, which apparently contributes to
      neuronal death of cerebellar granule cells in culture. We examined the role of
      muscarinic receptors in MeHg-induced Ca2+ dysregulation and cell death in rat
      cerebellar granule cells in vitro using fura-2 single-cell microfluorimetry and
      viability assays, respectively. The nonspecific muscarinic receptor antagonist
      atropine significantly delayed the onset of MeHg-induced Ca2+ elevations and
      reduced the amount of Ca2+ released into the cytosol. Depletion of the smooth
      endoplasmic reticulum (SER) Ca2+ pool with thapsigargin or down-regulation of
      muscarinic receptors and inositol-1,3,4-triphosphate (IP3) receptors with
      bethanechol (BCh) caused similar reductions in the amplitude of the MeHg-induced
      Ca2+ increase, suggesting that MeHg interacts with muscarinic receptors to cause
      Ca2+ release from the SER through activation of the IP3 receptors. To determine
      whether this Ca2+ release plays a role in MeHg-induced cell death, cells were
      exposed to MeHg in the presence of specific muscarinic receptor inhibitors. Acute
      exposure to increasing concentrations of MeHg (0.2-1.0 microM) caused a
      corresponding increase in cell death at 24.5 h post-exposure. Prior down
      regulation of muscarinic and IP3receptors with BCh protected against cell death.
      Protection was ablated by atropine and the M3 receptor antagonist 4
      diphenylacetoxyl-N-methylpiperidine methiodide (DAMP), but not by the neuronal
      nicotinic receptor antagonist dihydro-beta-erythroidine hydrobromide (DHE). Thus
      activation of M3 muscarinic receptors with subsequent generation of IP3 evidently
      contributes to elevated [Ca2+]i and subsequent cytotoxicity of cerebellar granule
      cells by MeHg.

PMID- 15141109
TI  - Evaluation of molecular similarity and molecular diversity methods using
      biological activity data.
AB  - This chapter reviews the techniques available for quantifying the effectiveness
      of methods for molecular similarity and molecular diversity, focusing in
      particular on similarity searching and on compound selection procedures. The
      evaluation criteria considered are based on biological activity data, both
      qualitative and quantitative, with rather different criteria needing to be used
      depending on the type of data available.

PMID- 15141110
TI  - A Web-based chemoinformatics system for drug discovery.
AB  - One of the key questions that must be addressed when implementing a
      chemoinformatics system is whether the tools will be designed for use by the
      expert user or by the "bench scientist." This decision can impact not only the
      style of tools that are rolled out, but is also a factor in terms of how these
      tools are delivered to the end users. The system that we outline here was
      designed for use by the non-expert user. As such, the tools that we discuss are
      in many cases simplified versions of some common algorithms used in
      chemoinformatics. In addition, the focus is on how to distribute these tools
      using a web-services interface, which greatly simplifies delivering new protocols
      to the end user.

PMID- 15141111
TI  - Application of chemoinformatics to high-throughput screening: practical
      considerations.
AB  - The objective of this chapter is to summarize and evaluate some of the most
      common chemoinformatic methods that are applied to the analysis of high
      throughput-screening data. The chapter will briefly describe current high
      throughput-screening practices and will stress how the major constraint on the
      application of chemoinformatics is often the quality of high-throughput-screening
      data. Discussion of the NCI dataset and how it differs from most high-throughput
      screening datasets will be made to highlight this point.

PMID- 15141112
TI  - Strategies for the identification and generation of informative compound sets.
AB  - Mounting pressures in pharmaceutical research necessitate ever increasing
      efficiency to lower cost and produce results. This is especially true in the
      realm of high-throughput screening (HTS) where large pharmaceutical companies
      historically test many hundreds of thousands of compounds in the search for new
      drug leads. As a result of this pressure the old mantra of "screen them all" is
      rapidly becoming a phrase of the past and the search for new, more efficient
      methods for discovering leads begins. This chapter will describe some of the
      methods, techniques, and strategies that have been implemented at Pharmacia that
      attempt to identify compounds that are likely to provide the most useful
      information so that one might discover solid leads rapidly.

PMID- 15141113
TI  - Methods for applying the quantitative structure-activity relationship paradigm.
AB  - There are several Quantitative Structure-Activity Relationship (QSAR) methods to
      assist in the design of compounds for medicinal use. Owing to the different QSAR
      methodologies, deciding which QSAR method to use depends on the composition of
      system of interest and the desired results. The relationship between a compound's
      binding affinity/activity to its structural properties was first noted in the
      1930s by Hammett and later refined by Hansch and Fujita in the mid-1960s. In 1988
      Cramer and coworkers created Comparative Molecular Field Analysis (CoMFA)
      incorporating the three-dimensional (3D) aspects of the compounds, specifically
      the electrostatic fields of the compound, into the QSAR model. Hopfinger and
      coworkers included an additional dimension to 3D-QSAR methodology in 1997 that
      eliminated the question of "Which conformation to use in a QSAR study?", creating
      4D-QSAR. In 1999 Chemical Computing Group Inc. (CCG) developed the Binary-QSAR
      methodology and added novel 3D-QSAR descriptors to the traditional QSAR model
      allowing the 3D properties of compounds to be incorporated into the traditional
      QSAR model. Recently CCG released Probabilistic Receptor Potentials to calculate
      the substrate's atomic preferences in the active site. These potentials are
      constructed by fitting analytical functions to experimental properties of the
      substrates using knowledge-based methods. An overview of these and other QSAR
      methods will be discussed along with an in-depth examination of the methodologies
      used to construct QSAR models. Also, included in this chapter is a case study of
      molecules used to create QSAR models utilizing different methodologies and QSAR
      programs.

PMID- 15141114
TI  - D-LogP: an alignment-free 3D description of local lipophilicity for QSAR studies.
AB  - The major hurdle to overcome in the development of 3D-QSAR models using steric,
      electrostatic, or lipophilic "fields" is related to both conformation selection
      and subsequent suitable overlay (alignment) of compounds. Therefore, it is of
      some interest to provide a conformationally sensitive lipophilicity descriptor
      that is alignment-independent. In this chapter we describe the derivation and
      parametrization of a new descriptor called 3D-LogP and demonstrate both its
      conformational sensitivity and its effectiveness in QSAR analysis. The 3D-LogP
      descriptor provides such a representation in the form of a rapidly computable
      description of the local lipophilicity at points on a user-defined molecular
      surface.

PMID- 15141115
TI  - Derivation and applications of molecular descriptors based on approximate surface
      area.
AB  - Three sets of molecular descriptors that can be computed from a molecular
      connection table are defined. The descriptors are based on the subdivision and
      classification of the molecular surface area according to atomic properties (such
      as contribution to logP, molar refractivity, and partial charge). The resulting
      32 descriptors are shown (a) to be weakly correlated with each other; (b) to
      encode many traditional molecular descriptors; and (c) to be useful for QSAR,
      QSPAR, and compound classification.

PMID- 15141116
TI  - Cell-based partitioning.
AB  - Partitioning techniques are widely used to classify compound sets or databases
      according to specific chemical or biological criteria. Partitioning is
      conceptually related to, yet algorithmically distinct from, conventional
      clustering methods and is particularly suitable for efficient processing of very
      large compound sets. Currently, some of the most popular partitioning approaches
      in the chemoinformatics field involve dimension reduction of initially defined
      chemistry spaces and creation of subsections of low-dimensional space for
      molecular classification. These subsections are often called cells. Original
      chemical reference spaces are generated through selection of various descriptors
      of molecular structure and properties. Principles and methodological aspects of
      dimension reduction of chemical spaces and compound partitioning in low
      dimensional space are described herein.

PMID- 15141117
TI  - Partitioning in binary-transformed chemical descriptor spaces.
AB  - Here we describe a statistically based partitioning method called median
      partitioning (MP), which involves the transformation of value distributions of
      molecular property descriptors into a binary classification scheme. The MP
      approach fundamentally differs from other partitioning approaches that involve
      dimension reduction of chemical spaces such as cell-based partitioning, since MP
      directly operates in original, albeit simplified, chemical space. Modified
      versions of the MP algorithm have been implemented and successfully applied in
      diversity selection, compound classification, and virtual screening. These
      findings have demonstrated that dimension reduction techniques, although elegant
      in their design, are not necessarily required for effective partitioning of
      molecular datasets. An attractive feature of statistical partitioning approaches
      such as decision tree methods or MP is their computational efficiency, which is
      becoming an important criterion for the analysis of compound databases containing
      millions of molecules.

PMID- 15141118
TI  - Comparison of methods based on diversity and similarity for molecule selection
      and the analysis of drug discovery data.
AB  - The concepts of diversity and similarity of molecules are widely used in
      quantitative methods for designing (selecting) a representative set of molecules
      and for analyzing the relationship between chemical structure and biological
      activity. We review methods and algorithms for design of a diverse set of
      molecules in the chemical space using clustering, cell-based partitioning, or
      other distance-based approaches. Analogous cell-based and clustering methods are
      described for analyzing drug-discovery data to predict activity in virtual
      screening. Some performance comparisons are made. The choice of descriptor
      variables to characterize chemical structure is also included in the comparative
      study. We find that the diversity of a selected set is quite sensitive to both
      the statistical selection method and the choice of molecular descriptors and
      that, for the dataset used in this study, random selection works surprisingly
      well in providing a set of data for analysis.

PMID- 15141119
TI  - Using recursive partitioning analysis to evaluate compound selection methods.
AB  - The design and analysis of a screening set for high throughput screening is
      complex. We examine three statistical strategies for compound selection, random,
      clustering, and space-filling. We examine two types of chemical descriptors,
      BCUTs and principal components of Dragon Constitutional descriptors. Based on the
      predictive power of multiple tree recursive partitioning, we reached the
      following tentative conclusions. Random designs appear to be as good as
      clustering and space-filling designs. For analysis, BCUTs appear to be better
      than principal components scores based upon Constitutional Descriptors. We
      confirm previous results that model-based selection of compounds can lead to
      improved screening hit rates.

PMID- 15141120
TI  - Designing combinatorial libraries optimized on multiple objectives.
AB  - The recent emphasis in combinatorial library design has shifted from the design
      of very large diverse libraries to the design of smaller more focused libraries.
      Typically the aim is to incorporate as much knowledge into the design as
      possible. This knowledge may relate to the target protein itself or may be
      derived from known active and inactive compounds. Other factors should also be
      taken into account, such as the cost of the library and the physicochemical
      properties of the compounds that are contained within the library. Thus, library
      design is a multi objective optimization problem. Most approaches to optimizing
      multiple objectives are based on aggregation methods whereby the objectives are
      assigned relative weights and are combined into a single fitness function. A more
      recent approach involves the use of a Multiobjective Genetic Algorithm in which
      the individual objectives are handled independently without the need to assign
      weights. The result is a family of solutions each of which represents a different
      compromise in the objectives. Thus, the library designer is able to make an
      informed choice on an appropriate compromise solution.

PMID- 15141121
TI  - Approaches to target class combinatorial library design.
AB  - The wealth of information available from the solution of the human genome has
      dramatically altered the nature of combinatorial library design. While single
      target-focused library design remains an important objective, creation of
      libraries directed toward families of receptors such as GPCRs, kinases, nuclear
      hormone receptors, and proteases, has replaced the generation of libraries based
      primarily on diversity. Although diversity-based design still plays a role for
      receptors with no known ligands, more knowledge-based approaches are required for
      target class design. This chapter discusses some of the possible design methods
      and presents examples where they are available.

PMID- 15141122
TI  - Simulated annealing: an effective stochastic optimization approach to
      computational library design.
AB  - We describe here a stochastic optimization protocol for computational library
      design based on the principle of simulated annealing (SA). We also demonstrate
      via computer simulation studies that the SA-guided diversity sampling affords
      higher information content than random sampling in terms of cluster hit rates.
      Using a tripeptoid library, we show that the SA guided similarity focusing
      provides important information about reagent selection for combinatorial
      synthesis. Finally, we report a system that employs the SA protocol for the
      simultaneous optimization of multiple properties during library design. We
      propose that the SA technique is an effective optimization method for
      computational library design.

PMID- 15141123
TI  - Genetic algorithms for classification of olfactory stimulants.
AB  - We have developed and tested a genetic algorithm (GA) for pattern recognition,
      which identifies molecular descriptors that optimize the separation of the
      activity classes of olfactory stimulants in a plot of the two or three largest
      principal components of the data. Because principal components maximize variance,
      the bulk of the information encoded by these descriptors is about differences
      between olfactory classes in the dataset. In addition, the GA focuses on those
      classes and or samples that are difficult to classify as it trains using a form
      of boosting to modify the fitness landscape. Boosting minimizes the problem of
      convergence to a local optimum, because the fitness function of the GA is
      changing as the population is evolving toward a solution. Over time, compounds
      that consistently classify correctly are not as heavily weighted in the analysis
      as compounds that are difficult to classify. The pattern recognition GA learns
      its optimal parameters in a manner similar to a neural network. The algorithm
      integrates aspects of both strong and weak learning to yield a "smart" one-pass
      procedure for feature selection and classification.

PMID- 15141124
TI  - How to describe chirality and conformational flexibility.
AB  - Given atomic coordinates for a particular conformation of a molecule and some
      property value assigned to each atom, one can easily calculate a chirality
      function that distinguishes enantiomers, is zero for an achiral molecule, and is
      a continuous function of the coordinates and properties. This is useful as a
      quantitative measure of chirality for molecular modeling and structure-activity
      relations.

PMID- 15141125
TI  - Novel scoring methods in virtual ligand screening.
AB  - Several different approaches have been proposed in the last decade to assess the
      binding affinity of a virtual small molecule ligand to a target protein,
      particularly with respect to screening large compound databases. Here we review
      the methods that have been proposed, and discuss techniques for optimizing
      scoring functions that have been applied in industrial settings.

PMID- 15141126
TI  - Prediction of drug-like molecular properties: modeling cytochrome p450
      interactions.
AB  - Preventing drug-drug interactions and reducing drug-related mortalities dictate
      cleaner and costlier medicines. The cost to bring a new drug to market has
      increased dramatically over the last 10 years, with post-discovery activities
      (preclinical and clinical) costs representing the majority of the spend. With the
      ever-increasing scrutiny that new drug candidates undergo in the post-discovery
      assessment phases, there is increasing pressure on discovery to deliver higher
      quality drug candidates. Given that compound attrition in the early clinical
      stages can often be attributed to metabolic liabilities, it has been of great
      interest lately to implement predictive measures of metabolic stability/
      liability in the drug design stage of discovery. The solution to this issue is
      wrapped in understanding the basic of the cytochrome P450 (CYP) enzymes functions
      and structures. Recently, experimental information on the structure of a variety
      of cytochrome P450 enzymes, major contributors to phase I metabolism, has become
      readily available. This, coupled with the availability of experimental
      information on substrate specificities, has lead to the development of numerous
      computational models (macromolecular, pharmacophore, and structure-activity) for
      the rationalization and prediction of CYP liabilities. A comprehensive review of
      these models is presented in this chapter.

PMID- 15141127
TI  - Psychometric structure of a comprehensive objective structured clinical
      examination: a factor analytic approach.
AB  - PROBLEM STATEMENT AND BACKGROUND: While the psychometric properties of Objective
      Structured Clinical Examinations (OSCEs) have been studied, their latent
      structures have not been well characterized. This study examines a factor
      analytic model of a comprehensive OSCE and addresses implications for measurement
      of clinical performance. METHODS: An exploratory maximum likelihood factor
      analysis with a Promax rotation was used to derive latent structures for the
      OSCE. RESULTS: A model with two correlated factors fit the data well. The first
      factor was related to Physical Examination and History-Taking was labeled as
      information gathering, while the second factor was related to Differential
      Diagnosis/Clinical Reasoning, and Patient Interaction and was labeled as
      reasoning and information dissemination. Case Management did not contribute to
      either factor. The factors accounted for a total 61.6% of the variance in the
      skills variables. CONCLUSIONS: Recognizing the psychometric components of OSCEs
      may support and enhance the use of OSCEs for measuring clinical competency of
      medical students.

PMID- 15141128
TI  - A qualitative study of resident learning in ambulatory clinic. The importance of
      exposure to 'breakdown' in settings that support effective response.
AB  - Qualitative analysis of a large ethnographic database from observations of a
      resident teaching clinic revealed three important findings. The first finding was
      that breakdown, a situation where an 'actor' (such as a person or the group) is
      not achieving expected effectiveness, was the most important category because of
      its frequency and explanatory power. The next finding was that exposure to
      breakdown was a necessary ingredient for reflective learning. The final finding
      was that effective response to breakdown (with concomitant reflective learning)
      requires six factors to be present: the patient is engaged directly;
      responsibility is matched to authority; tools are matched to tasks; information
      resources are matched to need; values are matched between co-participants; and
      expectations are matched with capacity. These findings have implications for
      planning, improvements and further studies in ambulatory teaching clinics.

PMID- 15141129
TI  - In pursuit of expertise. Toward an educational model for expertise development.
AB  - Firstly, the many characteristics of expertise are examined: they include aspects
      of pattern recognition, knowledge, skill, flexibility, metacognitive monitoring,
      available cognitive space and teaching abilities. Secondly, three educational
      models from different domains (Nursing, Surgical Education, Education) are
      analysed, compared and contrasted, in relation to both educational approach and
      the development of expertise. Thirdly, a new model for the development of
      expertise is proposed, incorporating aspects of each of the three previously
      discussed models. Within this new model, four phases of development are proposed,
      culminating in the achievement of expertise. Furthermore, it is noted that under
      certain circumstances performance can deteriorate, and that with appropriate
      support, there can be recursion back through earlier phases of development.
      Significant implications for both healthcare education and practice are
      discussed, in relation to concepts of expertise, potential educational approaches
      and the proposed model for the development of expertise.

PMID- 15141130
TI  - Use of the paired-comparison technique to determine the most valued qualities of
      the McMaster Medical Programme Admissions Process.
AB  - The Undergraduate Medical Programme at McMaster University selects students using
      a comprehensive set of tools. Attempts to modify the selection process over many
      years have been impeded by an inability to reconcile very strongly held views
      among stakeholders as to the importance of the selection tools and, indeed, the
      very purposes of the admission process. The objective of this study was to
      identify key 'qualities' of the selection process and to measure their relative
      importance to admissions process assessors. Through a qualitative review of
      internal research documents, Medical Programme Admissions Committee meeting
      minutes, memos and accreditation surveys eight qualities of the admissions
      process were identified: validity, fairness, accessibility, comprehensiveness,
      affordability, legal defensibility, contribution to class diversity and the role
      of the process as a public statement of the Programme's values. Faculty, students
      and community admissions assessors were surveyed, by mail, using a paired
      comparisons technique. The overall response rate was 58%. By a wide margin, all
      three groups of admissions assessors valued validity and fairness most highly.
      The least valued qualities were affordability and the role of the process as a
      statement of our values. Possible applications of this approach to the admissions
      process deliberations are discussed.

PMID- 15141131
TI  - The lore of admissions policies: contrasting formal and informal understandings
      of the residency selection process.
AB  - PURPOSE: The selection process for residency positions is sometimes seen as being
      "opaque" and unfair by students, and can be a significant source of student
      stress. Yet efforts to clarify the process may not have helped reduce student
      stress for a number of reasons. This paper examines the nature of the knowledge
      that students possess and describes the implications for future efforts at
      addressing this knowledge. METHODS: The current study assessed the perceptions of
      three groups (selection committee members, faculty advisors, and students) at a
      single institution using two evaluation methods (ranking of a context-free list
      of variables, and an assessment of the legitimacy of 20 "common language" opinion
      statements comparing the variables). RESULTS: For the context-free ranking of
      variables, ICC's were moderately high for all three groups (0.479-0.584) and the
      disattenuated correlations were very high (0.872 to 0.946). By contrast, when
      more contextually relevant opinion statements were evaluated, the ICC's were much
      more variable (less than 0 to 0.279), the correlations (where calculable) were
      lower (0.449 to 0.547), and inconsistencies of opinion regarding particular
      variables became apparent. CONCLUSIONS: To properly understand the true nature of
      the opinions that are being held by the various groups it is necessary to use
      statements that reflect the vernacular of the "rumour mills" that are the common
      source of student information.

PMID- 15141132
TI  - Investigating the reliability of the medical school admissions interview.
AB  - PURPOSE: Determining the valid and fair use of the interview for medical school
      admissions is contingent upon a demonstration of the reproducibility of interview
      scores. This study seeks to establish the generalizability of interview scores,
      first assessing the existing research evidence, and then analyzing data from a
      non-experimental independent replications research design. METHODS: Multivariate
      and univariate generalizability analyses are conducted using data from a
      structured interview obtained from a population of medical school applicants over
      two years. RESULTS: The existing literature does not provide sufficient evidence
      regarding interview reliability. In this study, interview scores derived from a
      standardized interview were found to display low to moderate levels of
      reliability. Interview scores do not appear to possess the level of precision
      found with other measures commonly used to facilitate admissions decisions.
      DISCUSSION/CONCLUSION: Given the results obtained, the fairness of using the
      interview as a highly influential component of the admission process is called
      into question. Methods for using interview data in a psychometrically defensible
      fashion are discussed. Specifically, attention to decision reliability provides
      guidance on how interview scores can best be integrated into the admissions
      process.

PMID- 15141133
TI  - Where judgement fails: pitfalls in the selection process for medical personnel.
AB  - Despite the critical importance of maintaining a valid and transparent selection
      process that serves the values held by all stakeholders involved in medical
      education (i.e., students, faculty, society), there continue to be problems with
      the current state of available admissions protocols. Some problems derive from
      inertia induced by inaccurate intuitions pertaining to the nature of admissions
      protocols and the underlying qualities being measured. Others arise from the lack
      of reliable and valid admissions protocols to capture the non-cognitive qualities
      of candidates. Still other issues arise from the problem of rumor-based
      perceptions regarding the qualities for which selection protocols select. Three
      articles in this issue of Advances in Health Sciences Education present evidence
      pertaining to the selection of medical personnel. This commentary represents an
      attempt to bind together these unique perspectives on the admissions process
      while also casting light on other ways in which human judgment can fail in this
      domain in the hope that it might help steer decision-makers away from these
      pitfalls.

PMID- 15141134
TI  - Residential traffic density and cancer incidence in Amsterdam, 1989-1997.
AB  - OBJECTIVE: To examine the association between cancer incidence in 1989-1997 in
      Amsterdam and residential traffic intensity. METHODS: We linked data on the daily
      traffic intensity for individual addresses along the main roads with the
      population-based regional cancer registry. Information on smoking habits was
      derived from a smoking survey. RESULTS: During 1989-1997, 27,157 cancer cases
      were diagnosed in Amsterdam residents. Using the age group- and sex-specific
      cancer incidence in the population not residing along the main roads as a
      reference, the standardized incidence ratio (SIR) of the population residing
      along the main roads was 1.03, (3384 cases), while the 95% confidence interval
      (CI) included unity (1.00-1.07). For most cancer sites the SIR was close to one,
      except for gastrointestinal cancer in males (SIR 1.16, CI: 1.04, 1.28), cancer of
      the respiratory tract in females (SIR 1.13, CI: 0.97, 1.31) and hematological
      malignancies in adult females (SIR 1.23, CI: 1.04, 1.44). Five cases of acute
      lymphocytic leukemia were diagnosed in children along the main roads (SIR 2.5,
      CI: 0.8, 5.9). Smoking habits did not differ between residents along the main
      roads and those living along other roads. CONCLUSIONS: We found no clear evidence
      for an association between residence along main roads and the incidence of cancer
      in adults, but we cannot exclude an association with hematological malignancies
      in females and children.

PMID- 15141135
TI  - Smoking and cancer risk in Korean men and women.
AB  - OBJECTIVE: In Korea, male smoking prevalence is among the world's highest, and
      mortality rates from smoking-caused cancers, particularly lung cancer, are
      escalating. This cohort study examined the effects of cigarette smoking on the
      risk of cancer mortality and incidence, and characterized the relationship of
      cancer risk with the amount and duration of cigarette smoking. METHOD: A nine
      year prospective cohort study was carried out on 1,212,906 Koreans, 30-95 years
      of age. The study population includes participants in a national insurance
      program, who completed a questionnaire on smoking and other risk factors. The
      main outcome measures were death from cancer and cancer incidence, obtained
      through record linkage. At baseline, 472,970 men (57.0%) and 20,548 (5.4%) women
      were current cigarette smokers. RESULTS: In multivariate Cox proportional hazards
      models, controlling for age, current smoking among men increased the risks of
      mortality for cancer of the lung (relative risk (RR), 4.6; 95% confidence
      interval (CI), 4.0-5.3) and other cancers, including larynx, bile duct,
      esophagus, liver, stomach, pancreas, bladder, and also leukemia. Current smoking
      among women increased the risk of lung cancer mortality (RR = 2.5, 95% CI = 2.0
      3.1). Similar results were found for incidence among men and women. CONCLUSION:
      In Korea, smoking is an independent risk factor for a number of major cancers.
      The findings affirm the need for aggressive tobacco control in Korea in order to
      minimize the epidemic of smoking-caused disease.

PMID- 15141136
TI  - Vegetables, fruit consumption and risk of lung cancer among middle-aged Japanese
      men and women: JPHC study.
AB  - OBJECTIVE: To investigate the association between vegetable and fruit consumption
      and incidence of lung cancer. METHODS: Self-administered questionnaires were used
      to assess diet in two large population-based cohorts with 42,224 and 51,114
      subjects in 1990 and 1993, respectively. After ten and seven years of follow-up,
      we ascertained 428 newly diagnosed case of lung cancer. Relative risk (RR)
      estimates were calculated using the Cox proportional hazards model with pooling
      of estimates from the two cohorts. RESULTS: Total vegetable and fruit intake was
      not associated with lowered risk of lung cancer, with RR approximating unity. The
      null relation between vegetable and fruit consumption and lung cancer incidence
      was consistent across strata of smoking status (never or ever smokers). When
      dividing lung cancers into adenocarcinoma and non-adenocarcinoma, risk for middle
      and high intakes of vegetables only, fruit only, and vegetables and fruit
      combined were all below one for non-adenocarcinoma and above one for
      adenocarcinoma, although no statistically significant differences were noted.
      Similar patterns of results were found when the two cohorts were analyzed
      separately. CONCLUSIONS: Contrary to popular belief, our results suggest that
      vegetables and fruit do not appear to confer protection from lung cancer.

PMID- 15141137
TI  - Coffee, tea and caffeine and risk of epithelial ovarian cancer.
AB  - OBJECTIVE: Studies evaluating the relationships between coffee, tea and caffeine
      and ovarian cancer risk have given inconsistent results. We have examined these
      associations using data from an Australian population-based case-control study.
      METHODS: Women with epithelial ovarian cancer (EOC) (n = 696) and control women
      selected from the Electoral Roll (n = 786) provided comprehensive reproductive
      and lifestyle data and completed a food frequency questionnaire. RESULTS:
      Increasing coffee consumption was associated with a decreased risk of invasive
      EOC ( p trend = 0.009) with an odds ratio (OR) of 0.51 (95% confidence interval
      (CI) 0.32-0.80) for consumption of >/=4 cups of coffee per day compared to non
      drinkers. The association was significant only for serous and endometrioid/clear
      cell histological subtypes. There was no association with borderline tumours (OR:
      1.20, 95% CI: 0.58-2.47). An inverse relationship was also seen between caffeine
      intake and EOC but tea consumption was not related to EOC (OR: 1.10 95% CI: 0.76
      1.61 for >/=4 cups/day versus none). CONCLUSIONS: As tea contributed
      significantly to caffeine intake in this population we conclude that the
      association we observed with coffee is not due to caffeine, but to other
      components within coffee. We suggest future studies consider the type as well as
      the amount of each beverage consumed.

PMID- 15141138
TI  - Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a
      review of epidemiological and experimental evidence.
AB  - OBJECTIVE: This study reviews epidemiological and experimental works dealing with
      the effects of dietary n -6 or n -3 polyunsaturated fatty acids (PUFA) on
      prostate cancer (PCa) development and PCa risk. METHODS: Systematic literature
      searches were made using Medline. The epidemiological studies reviewed
      (ecological, case-control, cohorts, and nested case-control) were those having
      tested the association of PCa risk with the dietary intake or the blood or
      adipose tissue levels of PUFA ( n -6 PUFA, n -3 PUFA, long-chain n -3 PUFA,
      linoleic acid, alpha -linolenic acid, arachidonic acid, eicosapentaenoic acid,
      docosahexaenoic acid), and with the dietary intake of fish and seafood.
      Experimental studies dealing with the effects of PUFA on PCa development in
      animal models or with PCa cell growth in vitro were also reviewed, as well as
      studies on the mechanisms of the effects of PUFA on PCa. RESULTS: There is no or
      little evidence of an association of linoleic or arachidonic acids with PCa risk.
      Most epidemiological studies failed to find an association of PCa risk with fish
      or long-chain n -3 PUFA intake, but two recent cohort studies did find an inverse
      association of fish consumption with the risk of the latest stages of PCa. alpha 
      linolenic acid intake was associated with an increase of PCa risk in a majority
      of epidemiological studies, but other studies did not find this association.
      Experimental work in vitro and in vivo, as well as mechanistic studies, support a
      protective effect of long-chain n -3 PUFA on PCa, but data on the effects of
      linoleic and alpha -linolenic acids are scarce. CONCLUSIONS: Long-chain n -3 PUFA
      from fish are possible promising nutrients for the dietary prevention of PCa, but
      to-date with little epidemiological support. In contrast, studies suggest that
      alpha -linolenic acid intake might be a risk factor. New work, both
      epidemiological and experimental, is awaited to clarify these results.

PMID- 15141139
TI  - Smoking and Hodgkin lymphoma risk in women United States.
AB  - OBJECTIVE: Smoking has received little consideration as a risk factor for Hodgkin
      lymphoma (HL) in women, despite recent significant findings in men and gender
      differences in HL incidence. We investigated the association of HL with lifetime
      cigarette smoking and household environmental tobacco smoke (ETS) exposure in
      women. METHODS: In data from a population-based case-control study in women ages
      19-79, we analyzed HL risk associated with self-reported smoking and household
      ETS exposure in 312 diagnostically re-reviewed cases and 325 random-digit dialing
      controls using logistic regression. Epstein-Barr virus (EBV) presence was
      determined in tumors of 269 cases. RESULTS: In 253 cases compared to 254 controls
      ages 19-44, risks of HL overall, and of nodular sclerosis and EBV-negative HL,
      were increased 50% with ETS exposure in childhood; for 11 cases of mixed
      cellularity (MC) HL, current smoking and adult ETS exposure also increased risk;
      for 24 cases of EBV-positive HL, risk was elevated for current smoking, greater
      smoking intensity and duration, and ETS exposure. In 59 cases and 71 controls
      ages 45-79, most smoking characteristics did not appear to affect risk.
      CONCLUSIONS: Apparent effects of current smoking on risks of MC HL and EBV
      positive HL and of household ETS on risk of all HL in young adult females may
      broaden the evidence implicating tobacco smoke exposures in HL etiology.

PMID- 15141140
TI  - Breast tissue organochlorine levels and metabolic genotypes in relation to breast
      cancer risk Canada.
AB  - Genes that metabolize the rate of clearance of environmental carcinogens may be
      candidate genes for cancer susceptibility. There is some data to suggest that
      exposure to environmental pesticides and other organochlorine pollutants is a
      risk factor to breast cancer. It is therefore reasonable to ask if variants in
      the genes responsible for the metabolic activation of organochlorines are
      associated with different tissue burdens of organochlorines and if these variants
      modify the risk of breast cancer in the population. We conducted a case-control
      study of women who underwent an excision biopsy for suspected breast cancer in a
      Toronto hospital from 1995 to 1997. Patients are residents of the Greater Toronto
      Area and are primarily Caucasian of European descent. Cases were women with
      invasive breast cancer (n = 70) and controls (n = 69) were women diagnosed with
      benign disease, frequency matched by age to cases. Levels of organochlorines were
      measured in benign breast tissue and seven polymorphisms in five candidate genes
      were genotyped. In general, women who carried inactive alleles of the GSTM1 had
      higher levels of breast organochlorines, and were at modestly increased risk of
      breast cancer (odds ratio = 2.2; 95% CI = 1.1-4.4). However, multiple comparisons
      were made and generally our data do not support the hypothesis that
      organochlorines increase the risk of breast cancer among subgroups of women with
      specific metabolic genotypes.

PMID- 15141141
TI  - Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in
      Connecticut United States women.
AB  - OBJECTIVE: To further investigate the role of prior medical conditions and
      medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the
      data from a population-based case-control study of NHL in Connecticut women.
      METHODS: A total of 601 histologically confirmed incident cases of NHL and 717
      population-based controls were included in this study. In-person interviews were
      administered using standardized, structured questionnaires to collect information
      on medical conditions and medication use. RESULTS: An increased risk was found
      among women who had a history of autoimmune disorders (such as rheumatoid
      arthritis, lupus erythematosus, Sjogren's syndrome, and multiple sclerosis),
      anemia, eczema, or psoriasis. An increased risk was also observed among women who
      had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was
      found for women who had scarlet fever or who had used estrogen replacement
      therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA
      reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with
      past medical history appeared to vary based on NHL subtypes, but the results were
      based on small number of exposed subjects. CONCLUSION: A relationship between
      certain prior medical conditions and medication use and risk of NHL was observed
      in this study. Further studies are warranted to confirm our findings.

PMID- 15141143
TI  - Long-term outcomes and complications of metallic stents for malignant esophageal
      stenoses.
AB  - Thirty patients with malignant esophageal stenosis underwent Ultraflex esophageal
      stent deployment and were followed up for a maximum of 29 months from June 1995
      to August 2001 in Tenri Hospital. Twelve stents were in the upper esophagus, and
      nine each in the middle and lower esophagus. The procedures were successful and
      dysphagia scores improved from 2.9 to 0.7. Major complications such as
      esophagorespiratory fistula, hematemesis, or airway compression occurred in 9
      patients, more often in the upper esophagus than in other parts of the esophagus,
      with no statistical difference. There was a significant difference in the onset
      of major complications between the upper and middle esophagus, as well as between
      the upper and middle-lower esophagus (p < 0.05), but no difference in mean
      survival time between locations, or patients with or without major complications.
      These results demonstrate that esophageal stent deployment is effective for
      relieving dysphagia and associating malnutrition. But major complications may
      occur in the upper esophagus more often and earlier than in other parts.

PMID- 15141142
TI  - Treatment of recurrent craniopharyngiomas.
AB  - One of the most common complications of craniopharyngioma treatment is
      recurrence. The outcomes of treatment for recurrent tumors with different
      modalities were evaluated. Of the 61 patients treated initially, 24 had
      recurrence during follow-up period (1-29 years, mean 11 years). Twenty-two
      patients underwent a total of 35 additional operations for recurrence. With
      reoperation, total surgical removal was achieved for four occasions (Group a),
      subtotal resection was achieved with 31 surgical procedures. Nineteen procedures
      (Group b) were done without radiotherapy and seven were followed by radiotherapy
      (Group c). Seven patients were treated with radiosurgery (Group d) with or
      without surgical resection. The surgical mortality rate for Group a was 50% which
      was higher than for initial operation, while for Group b 10.5% and none for
      Groups c and d. Good functional status was maintained at follow-up in 50% of
      survived patients for Group a, 14% for Group b, 57% for Group c and 86% for Group
      d. The 5-year recurrence free survival rate was 50% for Group a, 16% for Group b,
      80% for Group c, and 83.3% for Group d. The rate of recurrence free survival for
      Group b was significantly lower than Group c (P = 0.004) and Group d (P = 0.001).
      The recurrence free survival rates were higher for Groups c and d than for Group
      b. The mortality and morbidity higher in the Group a. Radiotherapy and
      radiosurgery are useful adjuncts for the treatment of recurrence, resulting in a
      high recurrent-free survival rate with better functional outcome.

PMID- 15141144
TI  - Effects of mefloquine usage on genetic polymorphism of Plasmodium falciparum in
      Thai-Myanmarese border.
AB  - We studied the polymorphism of msp-1, which encodes a major surface protein on
      the merozoite, isolated from blood samples from western Thailand in 1999. Our
      study area was a low-transmission area for malaria, where mefloquine has been
      used as an antimalarial drug since 1994. Forty-nine patients were confirmed to
      have contracted falciparum malaria twice within 24 weeks. The number of detected
      haplotypes in 49 patients was 89 at the first diagnosis and 68 at the second
      diagnosis. The mean number of haplotypes per patient significantly decreased from
      1.82 to 1.39 but the frequency distributions of msp-1 haplotypes did not change
      significantly with the use of mefloquine. Our study strongly suggests that the
      antigenic diversity of Plasmodium falciparum is retained during mefloquine
      therapy in low-transmission areas.

PMID- 15141146
TI  - Thyroid hormone synergizes with follicle stimulating hormone to inhibit apoptosis
      in porcine granulosa cells selectively from small follicles.
AB  - To investigate the effect of thyroid hormone on the proliferative activity and
      apoptosis of granulosa cells at the varying stages of follicular growth, porcine
      granulosa cells obtained from small (1-2 mm), medium (3-5 mm) and large (6-11 mm)
      follicles were cultured under a serum-free condition in the presence or absence
      of follicle stimulating hormone (FSH; 20 ng/ml), with or without triiodothyronine
      (T3; 10-8M). Relative viability, proliferative activity, and apoptosis of
      cultured granulosa cells were evaluated with 3-(4.5-dimethylahiazol-2-yl)-2,5
      diphenyltetrazolium bromide [MTT] assay, Ki67 expression and activated caspase-3
      protein expression, respectively. MTT assay showed that T3 had no significant
      effect on the relative viability of granulosa cells regardless of the follicle
      size. Ki67-positive rate in small follicle granulosa cells was augmented by
      treatment with FSH whereas it was not affected by T3. Furthermore, FSH treatment
      decreased activated caspase-3 protein-positive rate of small follicle granulosa
      cells. Relative to the treatment with FSH alone, concomitant treatment with FSH
      and T3 resulted in further decrease in caspase-3 protein-positive rate in small
      follicle granulosa cells. Treatment with T3 alone did not affect the caspase-3
      protein-positive rate. These results suggest that thyroid hormone synergizes with
      FSH to inhibit apoptosis in small follicle granulosa cells without affecting the
      proliferative potential of those cells.

PMID- 15141145
TI  - The immunoglobulin and complement levels in the active pulmonary sarcoidosis.
AB  - BACKGROUND AND AIM: In sarcoidosis patients the circulating immune complex levels
      are raised with the activation of the disease but their diagnostic role is not
      clear. These circulating immune complexes contain complement and immunoglobulins
      (Ig). Complement and immunoglobulins are mostly accumulated in active sarcoid
      lesions and in circulating immune complexes. Thus complement and Ig levels in
      circulation will be reduced in active sarcoidosis patients due to their higher
      deposition in sarcoid lesions. We tried to make an estimation about the activity
      of the disease through measuring the IgG, IgA, and IgM and complement (C3-C4)
      levels in the serum. METHODS: Thirty-two (8 men) sarcoidosis patients (with their
      symptoms, chest x-ray graphies, bronchioalveolar lavage findings and the other
      related WASOG criteria) were divided into two groups as active and inactive
      cases. We measured with the immunodiffusion method the immunoglobulin and
      complement parameters of these two groups and compared them with each other.
      RESULTS: Compared to the active group the IgG and IgA in serum were significantly
      higher in the inactive group (p < 0.001, p=0.07 ). Although statistically not
      significant the IgM and C3, C4 levels were higher too in the inactive group.
      CONCLUSIONS: The IgG, IgA, IgM and the complement levels in serum are higher in
      the inactive group. We think that these findings might be useful for the follow
      up of the disorder's activity in sarcoidosis patients. In order to prove these
      finding studies with larger volume are needed.

PMID- 15141147
TI  - Expression of mPOU protein in the human pituitary adenomas.
AB  - OBJECTIVE: mPOU is a POU protein classified as class VI. It is present in the
      pituitary gland as well as the brain, heart muscle, skeletal muscle, lung, and
      lymphocytes. In our previous investigation, mPOU bound to the Pit-1-binding DNA
      elements of the rat PRL gene, and promoted transcription of the GH and PRL genes.
      In this study, we immunohistologically investigated the expression of mPOU in
      pituitary adenomas. METHODS: 17 patients with pituitary adenoma underwent tumor
      excision by transsphenoidal approach at our hospital (PRL: 5, GH: 4, FSH: 1, non
      functioning: 7). The expression in the tissue sections was investigated using
      immunostaining (ABC method). RESULTS: In all GH-producing and PRL-producing
      adenomas, mPOU protein was specifically expressed, particularly in the nuclei.
      DISCUSSION: Pit-1 has been considered to be a factor determining the expression
      of GH and PRL genes, but mPOU may also be involved in the expression.

PMID- 15141148
TI  - Seed treatment and its implication for fungicide exposure assessment.
AB  - Farmers may be exposed to fungicides through both personal application and use of
      treated seed. Most epidemiology studies rely on personal application to assess
      exposure. We explored the extent of potential exposure via use of treated seed
      using data from a large cohort of licensed pesticide applicators from Iowa and
      North Carolina. Potential secondary fungicide exposure due to treated seed was
      calculated by crop by multiplying the average percent of seed treated by those
      reporting raising that crop but not applying fungicide. This potential exposure
      was present for every crop with treated seed (corn, soybean, wheat, cotton,
      potato, and peanut), and was highest for corn (71%) and soybean farmers (19%).
      Potential secondary fungicide exposure was more common in Iowa than in North
      Carolina since most Iowa farmers plant corn and soybeans and few report applying
      fungicides. Owing to its widespread use on corn, potential secondary captan
      exposure may occur among the 90% of the individuals planting corn. The relative
      intensity of secondary fungicide exposure associated with planting treated seed
      is anticipated to be lower than actively applying fungicide. Limited data suggest
      that exposure during planting may be approximately 4% of actively applying
      fungicide; while seed transfer operations may have similar levels of exposure to
      personal application (80-200%). Measurement data are necessary to characterize
      the patterns of exposure related to the use of fungicide-treated seed and to
      determine whether this route of exposure is an important contributor to fungicide
      exposure among farmers.

PMID- 15141149
TI  - Reconstructing population exposures from dose biomarkers: inhalation of
      trichloroethylene (TCE) as a case study.
AB  - Physiologically based pharmacokinetic (PBPK) modeling is a well-established
      toxicological tool designed to relate exposure to a target tissue dose. The
      emergence of federal and state programs for environmental health tracking and the
      availability of exposure monitoring through biomarkers creates the opportunity to
      apply PBPK models to estimate exposures to environmental contaminants from urine,
      blood, and tissue samples. However, reconstructing exposures for large
      populations is complicated by often having too few biomarker samples, large
      uncertainties about exposures, and large interindividual variability. In this
      paper, we use an illustrative case study to identify some of these difficulties,
      and for a process for confronting them by reconstructing population-scale
      exposures using Bayesian inference. The application consists of interpreting
      biomarker data from eight adult males with controlled exposures to
      trichloroethylene (TCE) as if the biomarkers were random samples from a large
      population with unknown exposure conditions. The TCE concentrations in blood from
      the individuals fell into two distinctly different groups even though the
      individuals were simultaneously in a single exposure chamber. We successfully
      reconstructed the exposure scenarios for both subgroups - although the
      reconstruction of one subgroup is different than what is believed to be the true
      experimental conditions. We were however unable to predict with high certainty
      the concentration of TCE in air.

PMID- 15141150
TI  - Urinary biomarkers of occupational N,N-dimethylformamide (DMF) exposure
      attributed to the dermal exposure.
AB  - OBJECTIVE: To evaluate whether the dermal exposure to N,N-dimethylformamide (DMF)
      exerts significant effects and to determine the unit increment of dermal exposure
      on the total body burden of two biomarkers in urine: metabolism-required N
      methylformamide (U-NMF) and non-metabolized DMF (U-DMF) in actual occupational
      environments. METHODS: Exposure via respiratory and dermal routes was assessed on
      an individual basis for 75 workers from four DMF-related factories directly
      exposed to DMF. Respiratory exposure was determined by breathing-zone sampling
      for a full-work shift, and dermal exposure was assessed on the palms and forearms
      of both hands by an adhesive tape-patch method. U-NMF and U-DMF collected
      immediately postshift were measured. RESULTS: The average concentrations of
      airborne DMF, DMF on hands and on forearms, U-NMF, and U-DMF (GM) were 1.51 ppm,
      0.04 microg/cm(2), 0.03 microg/cm(2), 0.47 mg/l, and 0.38 mg/l, respectively. In
      multiple linear regression tests, only airborne DMF and DMF on hands remained
      significantly (P<0.001) associated with U-NMF and U-DMF. Based on model
      estimates, the unit increment of hands' exposure (microg/cm(2)) could contribute
      to 0.53 and 0.46 mg/l of the increment of U-NMF and U-DMF, respectively, given a
      daily occupational airborne exposure to DMF at about 1.5 ppm. CONCLUSIONS: Dermal
      exposure provides a substantial contribution to the total body burden of DMF. A
      control remedy such as the enforcement of wearing impermeable gloves by workers
      occupationally exposed to DMF should be implemented with the highest priority.

PMID- 15141151
TI  - Understanding variability in time spent in selected locations for 7-12-year old
      children.
AB  - This paper summarizes a series of analyses of clustered, sequential
      activity/location data collected by Harvard University for 160 children aged 7-12
      years in Southern California (Geyh et al., 2000). The main purpose of the paper
      is to understand intra- and inter-variability in the time spent by the sample in
      the outdoor location, the location exhibiting the most variability of the ones
      evaluated. The data were analyzed using distribution-free hypothesis-testing (K-S
      tests of the distributions), generalized linear modeling techniques, and random
      sampling schemes that produced "cohorts" whose descriptive statistical
      characteristics were evaluated against the original dataset. Most importantly,
      our analyses indicate that subdividing the population into appropriate cohorts
      better replicates parameters of the original data, including the interclass
      correlation coefficient (ICC), which is a relative measure of the intra- and
      inter-individual variability inherent in the original data. While the findings of
      our analyses are consistent with previous assessments of "time budget" and
      physical activity data, they are constrained by the rather homogeneous sample
      available to us. Owing to a general lack of longitudinal human activity/location
      data available for other age/gender cohorts, we are unable to generalize our
      findings to other population subgroups.

PMID- 15141152
TI  - Occupational exposure to airborne asbestos from coatings, mastics, and adhesives.
AB  - Over the past few years, a question has arisen about the degree of exposure to
      airborne asbestos associated with the application, cleanup, and tear-out of glues
      and mastics used between 1940 and the present. These liquid products were used
      either to adhere insulation to pipes and boilers or to cover the insulation so as
      to protect it. In this study, four asbestos-containing products, a coating, two
      mastics, and an adhesive, which were representative of the various classes of
      products that have been used historically, were tested to determine the airborne
      concentration of asbestos fibers released during five different activities
      (application, spill cleanup, sanding, removal, and sweep cleaning). Each activity
      was performed for 30 min (often in triplicate). Personal (n=172) and area (n=280)
      air samples were collected during the tests, and each was analyzed for total
      fiber concentrations using phase contrast microscopy (PCM), and for asbestos
      fiber count using transmission electron microscopy (TEM). A measurable
      concentration of asbestos fibers was detected in six of the 452 samples collected
      (0.0017-0.0184 fibers/ml). The observed asbestos fibers counts for each product
      were similar to background. Only one asbestos fiber was detected in an indoor
      background sample; no asbestos fibers were identified in any of the outdoor
      background samples. The (raw) PCM-total fiber concentrations were adjusted based
      on TEM analyses that reported fraction of asbestos fibers (to derive a PCM
      asbestos concentration) and by the fraction of the 8-h workday that a worker
      spends performing the activity (to derive a calculated TWA). For the coatings,
      mastics, and adhesives evaluated in the present study, the calculated TWAs using
      hypothetical work scenarios were well below the current Occupational Safety and
      Health Administration (OSHA) Permissible Exposure Limit (PEL) of 0.1 fibers/ml.
      The calculated TWAs ranged from 0.03 to 0.009 fibers/ml. The actual concentration
      of airborne asbestos due to these products is almost certainly much less than the
      TWAs, and may be so low as to not be measurable. These results support the
      historical view that these products, over the past 50 years, did not pose an
      occupational health hazard under foreseeable uses.

PMID- 15141153
TI  - Validation of self-reported cellular phone use.
AB  - BACKGROUND: In recent years, concern has been raised over possible adverse health
      effects of cellular telephone use. In epidemiological studies of cancer risk
      associated with the use of cellular telephones, the validity of self-reported
      cellular phone use has been problematic. Up to now there is very little
      information published on this subject. METHODS: We conducted a study to validate
      the questionnaire used in an ongoing international case-control study on cellular
      phone use, the "Interphone study". Self-reported cellular phone use from 68 of
      104 participants who took part in our study was compared with information derived
      from the network providers over a period of 3 months (taken as the gold
      standard). RESULTS: Using Spearman's rank correlation, the correlation between
      self-reported phone use and information from the network providers for cellular
      phone use in terms of the number of calls per day was good (r=0.62, 95% CI: 0.45
      0.75), while that of the average duration of each call was rather moderate
      (r=0.34, 95% CI: 0.11-0.54). Similar results were found when Kappa coefficients
      were estimated. A value of r=0.56 (Spearman's correlation, CI: 0.38-0.70) was
      found for cumulative cellular phone use. CONCLUSION: Our study suggests that
      cellular phone use is easier to recall in terms of number of calls made than in
      terms of cumulative phone use and should thus be used as the basis for the dose
      response analysis.

PMID- 15141154
TI  - Measurement of dialkyl phosphate metabolites of organophosphorus pesticides in
      human urine using lyophilization with gas chromatography-tandem mass spectrometry
      and isotope dilution quantification.
AB  - Urinary dialkylphosphate (DAP) metabolites have been used to estimate human
      exposure to organophosphorus pesticides. We developed a method for quantifying
      the six DAP urinary metabolites of at least 28 organophosphorus pesticides using
      lyophilization and chemical derivatization followed by analysis using isotope
      dilution gas chromatography-tandem mass spectrometry (GC-MS/MS). Urine samples
      were spiked with stable isotope analogues of the DAPs and the water was removed
      from the samples using a lyophilizer. The dried residue was dissolved in
      acetonitrile and diethyl ether, and the DAPs were chemically derivatized to their
      respective chloropropyl phosphate esters. The chloropropyl phosphate esters were
      concentrated, and analyzed using GC-MS/MS. The limits of detection of the method
      were in the low microg/l (parts per billion) to mid pg/ml range (parts per
      trillion) with coefficients of variation of 7-14%. The use of stable isotope
      analogues as internal standards for each of these metabolites allows for sample
      specific adjustment for recovery and thus permits a high degree of accuracy and
      precision. Use of this method with approximately 1100 urine samples collected
      from pregnant women and children indicate that the low limits of detection allow
      this method to be used in general population studies.

PMID- 15141155
TI  - Design and sampling methodology for a large study of preschool children's
      aggregate exposures to persistent organic pollutants in their everyday
      environments.
AB  - Young children, because of their immaturity and their rapid development compared
      to adults, are considered to be more susceptible to the health effects of
      environmental pollutants. They are also more likely to be exposed to these
      pollutants, because of their continual exploration of their environments with all
      their senses. Although there has been increased emphasis in recent years on
      exposure research aimed at this specific susceptible population, there are still
      large gaps in the available data, especially in the area of chronic, low-level
      exposures of children in their home and school environments. A research program
      on preschool children's exposures was established in 1996 at the USEPA National
      Exposure Research Laboratory. The emphasis of this program is on children's
      aggregate exposures to common contaminants in their everyday environments, from
      multiple media, through all routes of exposure. The current research project,
      "Children's Total Exposure to Persistent Pesticides and Other Persistent Organic
      Pollutants," (CTEPP), is a pilot-scale study of the exposures of 257 children,
      ages 1(1/2)-5 years, and their primary adult caregivers to contaminants in their
      everyday surroundings. The contaminants of interest include several pesticides,
      phenols, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and
      phthalate esters. Field recruitment and data collection began in February 2000 in
      North Carolina and were completed in November 2001 in Ohio. This paper describes
      the design strategy, survey sampling, recruiting, and field methods for the CTEPP
      study.

PMID- 15141156
TI  - Highly efficient EIAV-mediated in utero gene transfer and expression in the major
      muscle groups affected by Duchenne muscular dystrophy.
AB  - Gene therapy for Duchenne muscular dystrophy has so far not been successful
      because of the difficulty in achieving efficient and permanent gene transfer to
      the large number of affected muscles and the development of immune reactions
      against vector and transgenic protein. In addition, the prenatal onset of disease
      complicates postnatal gene therapy. We have therefore proposed a fetal approach
      to overcome these barriers. We have applied beta-galactosidase expressing equine
      infectious anaemia virus (EIAV) lentiviruses pseudotyped with VSV-G by single or
      combined injection via different routes to the MF1 mouse fetus on day 15 of
      gestation and describe substantial gene delivery to the musculature. Highly
      efficient gene transfer to skeletal muscles, including the diaphragm and
      intercostal muscles, as well as to cardiac myocytes was observed and gene
      expression persisted for at least 15 months after administration of this
      integrating vector. These findings support the concept of in utero gene delivery
      for therapeutic and long-term prevention/correction of muscular dystrophies and
      pave the way for a future application in the clinic.

PMID- 15141157
TI  - Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma
      model.
AB  - The prognosis of patients with malignant glioma is extremely poor, despite the
      extensive surgical treatment that they receive and recent improvements in
      adjuvant radio- and chemotherapy. In the present study, we propose the use of
      gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of
      malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed
      excellent migratory ability and exerted inhibitory effects on the proliferation
      of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in
      vivo and showed that when they were inoculated into the contralateral hemisphere,
      they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted
      directly into the tumor localized mainly at the border between the 9L tumor cells
      and normal brain parenchyma, and also infiltrated into the tumor bed.
      Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth
      and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs
      by infection with an adenoviral vector encoding human interleukin-2 (IL-2)
      clearly augmented the antitumor effect and further prolonged the survival of
      tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle
      would be promising as a new therapeutic approach for refractory brain tumor.

PMID- 15141158
TI  - Molecular imaging of gene therapy for cancer.
AB  - Gene therapy of cancer has been one of the most exciting and elusive areas of
      scientific and clinical research in the past decade. One of the most critical
      issues for ensuring success of this therapy is the development of technology for
      noninvasive monitoring of the location, magnitude and duration of vector-mediated
      gene expression, as well as the distribution and targeting of vector particles in
      vivo. In recent years many advances have been made in high-resolution, in vivo
      imaging methods, including: radionuclide imaging, such as positron emission
      tomography (PET) and single photon emission tomography (SPECT), magnetic
      resonance (MR) imaging and spectroscopy, bioluminescence imaging and various
      fluorescence imaging techniques, including fluorescence-mediated tomography (FMT)
      and near-infrared fluorescence (NIRF) reflectance imaging. A variety of factors
      determine the choice of specific imaging system, some of them are the imaging
      requirements (single or repeated), intended use (animal or human) and spatial
      requirements (organs versus cellular resolution and depth). This review provides
      descriptions of modalities applicable to imaging different parameters of vector
      mediated gene expression in tumors and stem cell tracking in vivo.

PMID- 15141159
TI  - Tumor-specific gene expression using the survivin promoter is further increased
      by hypoxia.
AB  - Increasing evidence indicates that survivin, an inhibitor of apoptosis protein
      (IAP), is expressed in human cancer cells but is absent from most normal adult
      tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P)
      to direct therapeutic expression of a proapoptotic gene specifically in human
      tumor cells. First, we demonstrated that this promoter was highly active in human
      tumor cells but not in normal cells. Second, we found that Sur-P activity was
      upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's
      activity under hypoxia, we added a hypoxia-responsive element (HRE) from the
      vascular endothelial growth factor gene promoter in its 5' region, and showed
      that this combination resulted in a further increase in the level of gene
      expression in hypoxic tumor cells. Finally, we demonstrated that expression of an
      autocatalytic reverse caspase-3 gene by this promoter specifically induced
      apoptotic cell death in human tumor cells but not in normal cells. These findings
      support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel
      vectors for cancer gene therapy.

PMID- 15141160
TI  - Potential therapeutic applications of recombinant, invasive E. coli.
AB  - An invasive Escherichia coli expressing the inv gene from Yersinia
      pseudotuberculosis was used as a vector for protein delivery to mammalian
      epithelial cells. Upon incubation with beta1-integrin-expressing mammalian cells,
      the bacteria are internalized, allowing bacteria-encoded proteins to function
      from within the mammalian cell. These bacteria are eventually processed in the
      host phagosome where they are destroyed. Expression of listeriolysin O from
      Listeria monocytogenes in the bacterium and its subsequent release into the
      phagosome triggers the breakdown of the membrane, allowing the release of the
      bacterial content into the cytosol of host cells. Using this vector, we
      demonstrate delivery of a gene and intact, functional proteins into mammalian
      cells in which beta1-integrin is expressed and accessible. At a ratio of
      bacteria/mammalian cells compatible with the survival of the mammalian cells,
      protein delivery can be observed in the entire cell population in vitro, while
      gene transfer is far less efficient. Protein delivery can also be achieved in
      vivo in mouse tumour models and can be detected at least 96 h after inoculation.
      Functional, natural E. coli proteins are delivered in the process and can provide
      therapeutic benefit in vivo, when associated with prodrugs. This therapeutic
      effect is associated with infiltration of neutrophils, eosinophils, macrophages
      and to a lesser extent dendritic cells in the tumour mass.

PMID- 15141161
TI  - Structural basis for the selective inhibition of JNK1 by the scaffolding protein
      JIP1 and SP600125.
AB  - The c-jun N-terminal kinase (JNK) signaling pathway is regulated by JNK
      interacting protein-1 (JIP1), which is a scaffolding protein assembling the
      components of the JNK cascade. Overexpression of JIP1 deactivates the JNK pathway
      selectively by cytoplasmic retention of JNK and thereby inhibits gene expression
      mediated by JNK, which occurs in the nucleus. Here, we report the crystal
      structure of human JNK1 complexed with pepJIP1, the peptide fragment of JIP1,
      revealing its selectivity for JNK1 over other MAPKs and the allosteric inhibition
      mechanism. The van der Waals contacts by the three residues (Pro157, Leu160, and
      Leu162) of pepJIP1 and the hydrogen bonding between Glu329 of JNK1 and Arg156 of
      pepJIP1 are critical for the selective binding. Binding of the peptide also
      induces a hinge motion between the N- and C-terminal domains of JNK1 and distorts
      the ATP-binding cleft, reducing the affinity of the kinase for ATP. In addition,
      we also determined the ternary complex structure of pepJIP1-bound JNK1 complexed
      with SP600125, an ATP-competitive inhibitor of JNK, providing the basis for the
      JNK specificity of the compound.

PMID- 15141162
TI  - Asymmetric distribution of the apical plasma membrane during neurogenic divisions
      of mammalian neuroepithelial cells.
AB  - At the onset of neurogenesis in the mammalian central nervous system,
      neuroepithelial cells switch from symmetric, proliferative to asymmetric,
      neurogenic divisions. In analogy to the asymmetric division of Drosophila
      neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve
      a change in cleavage plane orientation from perpendicular (vertical cleavage) to
      parallel (horizontal cleavage) relative to the apical surface of the
      neuroepithelium. Here, we report, using TIS21-GFP knock-in mouse embryos to
      identify neurogenic neuroepithelial cells, that at the onset as well as advanced
      stages of neurogenesis the vast majority of neurogenic divisions, like
      proliferative divisions, show vertical cleavage planes. Remarkably, however,
      neurogenic divisions of neuroepithelial cells, but not proliferative ones,
      involve an asymmetric distribution to the daughter cells of the apical plasma
      membrane, which constitutes only a minute fraction (1-2%) of the entire
      neuroepithelial cell plasma membrane. Our results support a novel concept for the
      cell biological basis of asymmetric, neurogenic divisions of neuroepithelial
      cells in the mammalian central nervous system.

PMID- 15141164
TI  - BRG1/BRM and prohibitin are required for growth suppression by estrogen
      antagonists.
AB  - Estrogen antagonists are universally employed in the breast cancer therapy,
      although antagonist therapy is limited by the inevitable development of cellular
      resistance. The molecular mechanisms by which these agents inhibit cellular
      proliferation in breast cancer cells are not fully defined. Recent studies have
      shown the involvement of the E2F pathway in tamoxifen-induced growth arrest. We
      show that an E2F repressor, prohibitin, and the chromatin modifiers Brg1/Brm are
      required for estrogen antagonist-mediated growth suppression through the estrogen
      receptor, and that their recruitment to native promoter-bound E2F is induced via
      a JNK1 pathway. In addition, we demonstrate major mechanistic differences among
      the signaling pathways initiated by estrogen, estrogen deprivation, and estrogen
      antagonists. Collectively, these findings suggest that the prohibitin/Brg1/Brm
      node is a major cellular target for estrogen antagonists, and thereby also
      implicate prohibitin/Brg1/Brm as potentially important targets for breast cancer
      therapy.

PMID- 15141163
TI  - Assembly of a Ca2+-dependent BK channel signaling complex by binding to beta2
      adrenergic receptor.
AB  - Large-conductance voltage and Ca2+-activated potassium channels (BKCa) play a
      critical role in modulating contractile tone of smooth muscle, and neuronal
      processes. In most mammalian tissues, activation of beta-adrenergic receptors and
      protein kinase A (PKAc) increases BKCa channel activity, contributing to
      sympathetic nervous system/hormonal regulation of membrane excitability. Here we
      report the requirement of an association of the beta2-adrenergic receptor
      (beta2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring
      protein (AKAP79/150) for beta2 agonist regulation. beta2AR can simultaneously
      interact with both BKCa and L-type Ca2+ channels (Cav1.2) in vivo, which enables
      the assembly of a unique, highly localized signal transduction complex to mediate
      Ca2+- and phosphorylation-dependent modulation of BKCa current. Our findings
      reveal a novel function for G protein-coupled receptors as a scaffold to couple
      two families of ion channels into a physical and functional signaling complex to
      modulate beta-adrenergic regulation of membrane excitability.

PMID- 15141165
TI  - The unfolded protein response represses differentiation through the RPD3-SIN3
      histone deacetylase.
AB  - In Saccharomyces cerevisiae, splicing of HAC1 mRNA is initiated in response to
      the accumulation of unfolded proteins in the endoplasmic reticulum by the
      transmembrane kinase-endoribonuclease Ire1p. Spliced Hac1p (Hac1ip) is a negative
      regulator of differentiation responses to nitrogen starvation, pseudohyphal
      growth, and meiosis. Here we show that the RPD3-SIN3 histone deacetylase complex
      (HDAC), its catalytic activity, recruitment of the HDAC to the promoters of early
      meiotic genes (EMGs) by Ume6p, and the Ume6p DNA-binding site URS1 in the
      promoters of EMGs are required for nitrogen-mediated negative regulation of EMGs
      and meiosis by Hac1ip. Co-immunoprecipitation experiments demonstrated that
      Hac1ip can interact with the HDAC in vivo. Systematic analysis of double deletion
      strains revealed that HAC1 is a peripheral component of the HDAC. In summary,
      nitrogen-induced synthesis of Hac1ip and association of Hac1ip with the HDAC are
      physiological events in the regulation of EMGs by nutrients. These data also
      define for the first time a gene class that is under negative control by the UPR,
      and provide the framework for a novel mechanism through which bZIP proteins
      repress transcription.

PMID- 15141166
TI  - Functional integration of the histone acetyltransferase MOF into the dosage
      compensation complex.
AB  - Dosage compensation in flies involves doubling the transcription of genes on the
      single male X chromosome to match the combined expression level of the two female
      X chromosomes. Crucial for this activation is the acetylation of histone H4 by
      the histone acetyltransferase (HAT) MOF. In male cells, MOF resides in a complex
      (dosage compensation complex, DCC) with MSL proteins and noncoding roX RNA.
      Previous studies suggested that MOF's localization to the X chromosome was
      largely RNA-mediated. We now found that contact of the MOF chromo-related domain
      with roX RNA plays only a minor role in correct targeting to the X chromosome in
      vivo. Instead, a strong, direct interaction between a conserved MSL1 domain and a
      zinc finger within MOF's HAT domain is crucial. The functional consequences of
      this interaction were studied in vitro. Simultaneous contact of MOF with MSL1 and
      MSL3 led to its recruitment to chromatin, a dramatic stimulation of HAT activity
      and to improved substrate specificity. Activation of MOF's HAT activity upon
      integration into the DCC may serve to restrict the critical histone modification
      to the male X chromosome.

PMID- 15141167
TI  - Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for
      chromosome end-joining.
AB  - End-to-end fusion of critically shortened telomeres in higher eucaryotes is
      presumed to be mediated by nonhomologous end-joining (NHEJ). Here we describe two
      PCR-based methods to monitor telomere length and examine the fate of
      dysfunctional telomeres in Arabidopsis lacking the catalytic subunit of
      telomerase (TERT) and the DNA repair proteins Ku70 and Mre11. Primer extension
      telomere repeat amplification relies on the presence of an intact G-overhang, and
      thus measures functional telomere length. The minimum functional telomere length
      detected was 300-400 bp. PCR amplification and sequence analysis of chromosome
      fusion junctions revealed exonucleolytic digestion of dysfunctional ends prior to
      fusion. In ku70 tert mutants, there was a greater incidence of microhomology at
      the fusion junction than in tert mutants. In triple ku70 tert mre11 mutants,
      chromosome fusions were still detected, but microhomology at the junction was no
      longer favored. These data indicate that both Ku70 and Mre11 contribute to fusion
      of critically shortened telomeres in higher eucaryotes. Furthermore, Arabidopsis
      processes critically shortened telomeres as double-strand breaks, using a variety
      of end-joining pathways.

PMID- 15141168
TI  - Talin B is required for force transmission in morphogenesis of Dictyostelium.
AB  - Talin plays a key role in the assembly and stabilisation of focal adhesions, but
      whether it is directly involved in force transmission during morphogenesis
      remains to be elucidated. We show that the traction force of Dictyostelium cells
      mutant for one of its two talin genes talB is considerably smaller than that of
      wild-type cells, both in isolation and within tissues undergoing morphogenetic
      movement. The motility of mutant cells in tightly packed tissues in vivo or under
      strong resistance conditions in vitro was lower than that of wild-type cells, but
      their motility under low external force conditions was not impaired, indicating
      inefficient transmission of force in mutant cells. Antibody staining revealed
      that the talB gene product (talin B) exists as small units subjacent to the cell
      membrane at adhesion sites without forming large focal adhesion-like assemblies.
      The total amount of talin B on the cell membrane was larger in prestalk cells,
      which exert larger force than prespore cells during morphogenesis. We conclude
      that talin B is involved in force transmission between the cytoskeleton and cell
      exterior.

PMID- 15141171
TI  - South Africa's new voice.

PMID- 15141170
TI  - Think harder about ecstasy.

PMID- 15141169
TI  - HCMV IE2-mediated inhibition of HAT activity downregulates p53 function.
AB  - Targeting of cellular histone acetyltransferases (HATs) by viral proteins is
      important in the development of virus-associated diseases. The immediate-early 2
      protein (IE2) of human cytomegalovirus (HCMV) binds to the tumor suppressor, p53,
      and inactivates its functions by unknown mechanisms. Here, we show that IE2 binds
      to the HAT domain of the p53 coactivators, p300 and CREB-binding protein (CBP),
      and blocks their acetyltransferase activity on both histones and p53. The minimal
      HAT inactivation region on IE2 involves the N-terminal 98 amino acids. The in
      vivo DNA binding of p53 and local histone acetylation on p53-dependent promoters
      are all reduced by IE2, but not by mutant IE2 proteins that lack the HAT
      inhibition region. Furthermore, the p53 acetylation site mutant, K320/373/382R,
      retains both DNA binding and promoter transactivation activity in vivo and these
      effects are repressed by IE2 as well. Together with the finding that only wild
      type IE2 exerts an antiapoptotic effect, our results suggest that HCMV IE2
      downregulates p53-dependent gene activation by inhibiting p300/CBP-mediated local
      histone acetylation and that IE2 may have oncogenic activity.

PMID- 15141172
TI  - Iraqi killings prompt calls for US to evacuate weapons scientists.

PMID- 15141174
TI  - US intelligence exposed as student decodes Iraq memo.

PMID- 15141173
TI  - Bush pressured as Nancy Reagan pleads for stem-cell research.

PMID- 15141175
TI  - South Africa names head of science ministry.

PMID- 15141176
TI  - Researchers fear break-up of UK medical institute.

PMID- 15141177
TI  - Icelandic database shelved as court judges privacy in peril.

PMID- 15141178
TI  - Scientists complain government cash is no rise in real terms.

PMID- 15141179
TI  - NIH urged to rewrite rules on consultancies.

PMID- 15141180
TI  - Vaccine targets gut reaction to calm livestock wind.

PMID- 15141182
TI  - Geology: time lords.

PMID- 15141183
TI  - Psychedelic drugs: the ups and downs of ecstasy.

PMID- 15141184
TI  - Gene therapy needs both trials and new strategies.

PMID- 15141185
TI  - Biodiversity law has had some unintended effects.

PMID- 15141186
TI  - Putting Norway on the gene-therapy map.

PMID- 15141191
TI  - Heads and tails.

PMID- 15141192
TI  - Geophysics: a fuel-efficient geodynamo?

PMID- 15141194
TI  - Quantum physics: high NOON for photons.

PMID- 15141193
TI  - Signal transduction: thumbs up for inactivation.

PMID- 15141195
TI  - Membrane trafficking: dual-key strategy.

PMID- 15141197
TI  - Physiology: orphan detectors of metabolism.

PMID- 15141198
TI  - Muscle: the sliding filament at 50.

PMID- 15141200
TI  - Ageing and the mystery at Arles.

PMID- 15141201
TI  - Hyperactive antifreeze protein in a fish.
AB  - Fish that live in the polar oceans survive at low temperatures by virtue of
      'antifreeze' plasma proteins in the blood that bind to ice crystals and prevent
      these from growing. However, the antifreeze proteins isolated so far from the
      winter flounder (Pleuronectes americanus), a common fish in the Northern
      Hemisphere, are not sufficiently active to protect it from freezing in icy sea
      water. Here we describe a previously undiscovered antifreeze protein from this
      flounder that is extremely active (as effective as those found in insects) and
      which explains the resistance of this fish to freezing in polar and subpolar
      waters.

PMID- 15141202
TI  - Reproductive biology: delivering spermatozoan RNA to the oocyte.
AB  - Even though the genetic fingerprint of human sperm has been defined, its role in
      orchestrating fertilization and the development of the early embryo remains
      vague. Here we show that human male gametes pass over more to the oocyte than
      just the haploid male genome--paternal messenger RNAs are also delivered to the
      egg at fertilization. If these transcripts, previously thought to be left-overs
      from spermatogenesis, are important in early development, our findings may have
      implications for the success of somatic-cell nuclear transfer in cloning
      technology and the identification of components leading to unexplained male
      factor infertility.

PMID- 15141204
TI  - The formation of a massive protostar through the disk accretion of gas.
AB  - The formation of low-mass stars like our Sun can be explained by the
      gravitational collapse of a molecular cloud fragment into a protostellar core and
      the subsequent accretion of gas and dust from the surrounding interstellar
      medium. Theoretical considerations suggest that the radiation pressure from the
      protostar on the in-falling material may prevent the formation of stars above ten
      solar masses through this mechanism, although some calculations have claimed that
      stars up to 40 solar masses can in principle be formed via accretion through a
      disk. Given this uncertainty and the fact that most massive stars are born in
      dense clusters, it was suggested that high-mass stars are the result of the
      runaway merging of intermediate-mass stars. Here we report observations that
      clearly show a massive star being born from a large rotating accretion disk. The
      protostar has already assembled about 20 solar masses, and the accretion process
      is still going on. The gas reservoir of the circumstellar disk contains at least
      100 solar masses of additional gas, providing sufficient fuel for substantial
      further growth of the forming star.

PMID- 15141205
TI  - De Broglie wavelength of a non-local four-photon state.
AB  - Superposition is one of the most distinctive features of quantum theory and has
      been demonstrated in numerous single-particle interference experiments. Quantum
      entanglement, the coherent superposition of states in multi-particle systems,
      yields more complex phenomena. One important type of multi-particle experiment
      uses path-entangled number states, which exhibit pure higher-order interference
      and the potential for applications in metrology and imaging; these include
      quantum interferometry and spectroscopy with phase sensitivity at the Heisenberg
      limit, or quantum lithography beyond the classical diffraction limit. It has been
      generally understood that in optical implementations of such schemes, lower-order
      interference effects always decrease the overall performance at higher particle
      numbers. Such experiments have therefore been limited to two photons. Here we
      overcome this limitation, demonstrating a four-photon interferometer based on
      linear optics. We observe interference fringes with a periodicity of one-quarter
      of the single-photon wavelength, confirming the presence of a four-particle mode
      entangled state. We anticipate that this scheme should be extendable to arbitrary
      photon numbers, holding promise for realizable applications with entanglement
      enhanced performance.

PMID- 15141206
TI  - Super-resolving phase measurements with a multiphoton entangled state.
AB  - Interference phenomena are ubiquitous in physics, often forming the basis of
      demanding measurements. Examples include Ramsey interferometry in atomic
      spectroscopy, X-ray diffraction in crystallography and optical interferometry in
      gravitational-wave studies. It has been known for some time that the quantum
      property of entanglement can be exploited to perform super-sensitive
      measurements, for example in optical interferometry or atomic spectroscopy. The
      idea has been demonstrated for an entangled state of two photons, but for larger
      numbers of particles it is difficult to create the necessary multiparticle
      entangled states. Here we demonstrate experimentally a technique for producing a
      maximally entangled three-photon state from initially non-entangled photons. The
      method can in principle be applied to generate states of arbitrary photon number,
      giving arbitrarily large improvement in measurement resolution. The method of
      state construction requires non-unitary operations, which we perform using post
      selected linear-optics techniques similar to those used for linear-optics quantum
      computing.

PMID- 15141207
TI  - Increased seasonality in Middle East temperatures during the last interglacial
      period.
AB  - The last interglacial period (about 125,000 years ago) is thought to have been at
      least as warm as the present climate. Owing to changes in the Earth's orbit
      around the Sun, it is thought that insolation in the Northern Hemisphere varied
      more strongly than today on seasonal timescales, which would have led to
      corresponding changes in the seasonal temperature cycle. Here we present
      seasonally resolved proxy records using corals from the northernmost Red Sea,
      which record climate during the last interglacial period, the late Holocene epoch
      and the present. We find an increased seasonality in the temperature recorded in
      the last interglacial coral. Today, climate in the northern Red Sea is sensitive
      to the North Atlantic Oscillation, a climate oscillation that strongly influences
      winter temperatures and precipitation in the North Atlantic region. From our
      coral records and simulations with a coupled atmosphere-ocean circulation model,
      we conclude that a tendency towards the high-index state of the North Atlantic
      Oscillation during the last interglacial period, which is consistent with
      European proxy records, contributed to the larger amplitude of the seasonal cycle
      in the Middle East.

PMID- 15141208
TI  - Power requirement of the geodynamo from ohmic losses in numerical and laboratory
      dynamos.
AB  - In the Earth's fluid outer core, a dynamo process converts thermal and
      gravitational energy into magnetic energy. The power needed to sustain the
      geomagnetic field is set by the ohmic losses (dissipation due to electrical
      resistance). Recent estimates of ohmic losses cover a wide range, from 0.1 to 3.5
      TW, or roughly 0.3-10% of the Earth's surface heat flow. The energy requirement
      of the dynamo puts constraints on the thermal budget and evolution of the core
      through Earth's history. Here we use a set of numerical dynamo models to derive
      scaling relations between the core's characteristic dissipation time and the
      core's magnetic and hydrodynamic Reynolds numbers--dimensionless numbers that
      measure the ratio of advective transport to magnetic and viscous diffusion,
      respectively. The ohmic dissipation of the Karlsruhe dynamo experiment supports a
      simple dependence on the magnetic Reynolds number alone, indicating that flow
      turbulence in the experiment and in the Earth's core has little influence on its
      characteristic dissipation time. We use these results to predict moderate ohmic
      dissipation in the range of 0.2-0.5 TW, which removes the need for strong
      radioactive heating in the core and allows the age of the solid inner core to
      exceed 2.5 billion years.

PMID- 15141209
TI  - Optimal nitrogen-to-phosphorus stoichiometry of phytoplankton.
AB  - Redfield noted the similarity between the average nitrogen-to-phosphorus ratio in
      plankton (N:P = 16 by atoms) and in deep oceanic waters (N:P = 15; refs 1, 2). He
      argued that this was neither a coincidence, nor the result of the plankton
      adapting to the oceanic stoichiometry, but rather that phytoplankton adjust the
      N:P stoichiometry of the ocean to meet their requirements through nitrogen
      fixation, an idea supported by recent modelling studies. But what determines the
      N:P requirements of phytoplankton? Here we use a stoichiometrically explicit
      model of phytoplankton physiology and resource competition to derive from first
      principles the optimal phytoplankton stoichiometry under diverse ecological
      scenarios. Competitive equilibrium favours greater allocation to P-poor resource
      acquisition machinery and therefore a higher N:P ratio; exponential growth
      favours greater allocation to P-rich assembly machinery and therefore a lower N:P
      ratio. P-limited environments favour slightly less allocation to assembly than N
      limited or light-limited environments. The model predicts that optimal N:P ratios
      will vary from 8.2 to 45.0, depending on the ecological conditions. Our results
      show that the canonical Redfield N:P ratio of 16 is not a universal biochemical
      optimum, but instead represents an average of species-specific N:P ratios.

PMID- 15141210
TI  - Food-web interactions govern the resistance of communities after non-random
      extinctions.
AB  - Growing concern about how loss of biodiversity will affect ecosystems has
      stimulated numerous studies. Although most studies have assumed that species go
      extinct randomly, species often go extinct in order of their sensitivity to a
      stress that intensifies through time (such as climate change). Here we show that
      the consequences of random and ordered extinctions differ. Both depend on food
      web interactions that create compensation; that is, the increase of some species
      when their competitors and/or predators decrease in density due to environmental
      stress. Compensation makes communities as a whole more resistant to stress by
      reducing changes in combined species densities. As extinctions progress, the
      potential for compensation is depleted, and communities become progressively less
      resistant. For ordered extinctions, however, this depletion is offset and
      communities retain their resistance, because the surviving species have greater
      average resistance to the stress. Despite extinctions being ordered, changes in
      the food web with successive extinctions make it difficult to predict which
      species will show compensation in the future. This unpredictability argues for
      'whole-ecosystem' approaches to biodiversity conservation, as seemingly
      insignificant species may become important after other species go extinct.

PMID- 15141211
TI  - Resonance effects indicate a radical-pair mechanism for avian magnetic compass.
AB  - Migratory birds are known to use the geomagnetic field as a source of compass
      information. There are two competing hypotheses for the primary process
      underlying the avian magnetic compass, one involving magnetite, the other a
      magnetically sensitive chemical reaction. Here we show that oscillating magnetic
      fields disrupt the magnetic orientation behaviour of migratory birds. Robins were
      disoriented when exposed to a vertically aligned broadband (0.1-10 MHz) or a
      single-frequency (7-MHz) field in addition to the geomagnetic field. Moreover, in
      the 7-MHz oscillating field, this effect depended on the angle between the
      oscillating and the geomagnetic fields. The birds exhibited seasonally
      appropriate migratory orientation when the oscillating field was parallel to the
      geomagnetic field, but were disoriented when it was presented at a 24 degrees or
      48 degrees angle. These results are consistent with a resonance effect on singlet
      triplet transitions and suggest a magnetic compass based on a radical-pair
      mechanism.

PMID- 15141212
TI  - Modelling disease outbreaks in realistic urban social networks.
AB  - Most mathematical models for the spread of disease use differential equations
      based on uniform mixing assumptions or ad hoc models for the contact process.
      Here we explore the use of dynamic bipartite graphs to model the physical contact
      patterns that result from movements of individuals between specific locations.
      The graphs are generated by large-scale individual-based urban traffic
      simulations built on actual census, land-use and population-mobility data. We
      find that the contact network among people is a strongly connected small-world
      like graph with a well-defined scale for the degree distribution. However, the
      locations graph is scale-free, which allows highly efficient outbreak detection
      by placing sensors in the hubs of the locations network. Within this large-scale
      simulation framework, we then analyse the relative merits of several proposed
      mitigation strategies for smallpox spread. Our results suggest that outbreaks can
      be contained by a strategy of targeted vaccination combined with early detection
      without resorting to mass vaccination of a population.

PMID- 15141213
TI  - Citric acid cycle intermediates as ligands for orphan G-protein-coupled
      receptors.
AB  - The citric acid cycle is central to the regulation of energy homeostasis and cell
      metabolism. Mutations in enzymes that catalyse steps in the citric acid cycle
      result in human diseases with various clinical presentations. The intermediates
      of the citric acid cycle are present at micromolar concentration in blood and are
      regulated by respiration, metabolism and renal reabsorption/extrusion. Here we
      show that GPR91 (ref. 3), a previously orphan G-protein-coupled receptor (GPCR),
      functions as a receptor for the citric acid cycle intermediate succinate. We also
      report that GPR99 (ref. 4), a close relative of GPR91, responds to alpha
      ketoglutarate, another intermediate in the citric acid cycle. Thus by acting as
      ligands for GPCRs, succinate and alpha-ketoglutarate are found to have unexpected
      signalling functions beyond their traditional roles. Furthermore, we show that
      succinate increases blood pressure in animals. The succinate-induced hypertensive
      effect involves the renin-angiotensin system and is abolished in GPR91-deficient
      mice. Our results indicate a possible role for GPR91 in renovascular
      hypertension, a disease closely linked to atherosclerosis, diabetes and renal
      failure.

PMID- 15141214
TI  - Aquaporin-0 membrane junctions reveal the structure of a closed water pore.
AB  - The lens-specific water pore aquaporin-0 (AQP0) is the only aquaporin known to
      form membrane junctions in vivo. We show here that AQP0 from the lens core,
      containing some carboxy-terminally cleaved AQP0, forms double-layered crystals
      that recapitulate in vivo junctions. We present the structure of the AQP0
      membrane junction as determined by electron crystallography. The junction is
      formed by three localized interactions between AQP0 molecules in adjoining
      membranes, mainly mediated by proline residues conserved in AQP0s from different
      species but not present in most other aquaporins. Whereas all previously
      determined aquaporin structures show the pore in an open conformation, the water
      pore is closed in AQP0 junctions. The water pathway in AQP0 also contains an
      additional pore constriction, not seen in other known aquaporin structures, which
      may be responsible for pore gating.

PMID- 15141215
TI  - The GTPase-activating protein Rap1GAP uses a catalytic asparagine.
AB  - Rap1 is a Ras-like guanine-nucleotide-binding protein (GNBP) that is involved in
      a variety of signal-transduction processes. It regulates integrin-mediated cell
      adhesion and might activate extracellular signal-regulated kinase. Like other Ras
      like GNBPs, Rap1 is regulated by guanine-nucleotide-exchange factors (GEFs) and
      GTPase-activating proteins (GAPs). These GAPs increase the slow intrinsic GTPase
      reaction of Ras-like GNBPs by many orders of magnitude and allow tight regulation
      of signalling. The activation mechanism involves stabilization of the catalytic
      glutamine of the GNBP and, in most cases, the insertion of a catalytic arginine
      of GAP into the active site. Rap1 is a close homologue of Ras but does not
      possess the catalytic glutamine essential for GTP hydrolysis in all other Ras
      like and Galpha proteins. Furthermore, RapGAPs are not related to other GAPs and
      apparently do not use a catalytic arginine residue. Here we present the crystal
      structure of the catalytic domain of the Rap1-specific Rap1GAP at 2.9 A. By
      mutational analysis, fluorescence titration and stopped-flow kinetic assay, we
      demonstrate that Rap1GAP provides a catalytic asparagine to stimulate GTP
      hydrolysis. Implications for the disease tuberous sclerosis are discussed.

PMID- 15141219
TI  - Winds of change blow away the cobwebs on campus.

PMID- 15141216
TI  - A conformational switch controls hepatitis delta virus ribozyme catalysis.
AB  - Ribozymes enhance chemical reaction rates using many of the same catalytic
      strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site
      specific self-cleavage of the viral RNA phosphodiester backbone requires both
      divalent cations and a cytidine nucleotide. General acid-base catalysis,
      substrate destabilization and global and local conformational changes have all
      been proposed to contribute to the ribozyme catalytic mechanism. Here we report
      ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that
      cytidine is positioned to activate the 2'-OH nucleophile in the precursor
      structure. This observation supports its proposed role as a general base in the
      reaction mechanism. Comparison of crystal structures of the ribozyme in the pre-
      and post-cleavage states reveals a significant conformational change in the RNA
      after cleavage and that a catalytically critical divalent metal ion from the
      active site is ejected. The HDV ribozyme has remarkable chemical similarity to
      protein ribonucleases and to zymogens for which conformational dynamics are
      integral to biological activity. This finding implies that RNA structural
      rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.

PMID- 15141220
TI  - Curiosity makes way for capitalism.

PMID- 15141221
TI  - Will creativity thrive in an island paradise?

PMID- 15141222
TI  - Aerospace meets biotech.

PMID- 15141223
TI  - The yeast is rising.

PMID- 15141225
TI  - Scientists and societies. Young genomicists get connected.

PMID- 15141228
TI  - In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an
      antiapoptotic function of STAT3.
AB  - A characteristic feature of neoplastic transformation is a perpetual activation
      of oncogenic proteins. Here, we studied signal transducers and activators of
      transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell
      lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors
      showed frequent and intense nuclear staining with anti-PY-STAT3 antibody,
      indicating a constitutive activation of STAT3 in vivo in tumor stages. In
      contrast, only sporadic and faint staining was observed in indolent lesions of
      patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal
      Pautrier abscesses associated with early stages of MF did not express activated
      STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from
      an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or
      dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered
      a significant increase in tumor cells undergoing apoptosis, whereas forced
      expression of STAT3wt or empty vector had no effect. In conclusion, a profound in
      vivo activation of STAT3 is observed in MF tumors but not in the early stages of
      MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together,
      these findings suggest that STAT3 is a malignancy factor in CTCL.

PMID- 15141230
TI  - Embryonic stem cells: good to the bone?

PMID- 15141227
TI  - Structure of a complex between a voltage-gated calcium channel beta-subunit and
      an alpha-subunit domain.
AB  - Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and
      neurotransmitter release, neuronal migration, activation of calcium-dependent
      signalling cascades, and synaptic input integration. An essential Ca(V)
      intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain
      (the alpha-interaction domain, AID) between transmembrane domains I and II of the
      pore-forming alpha(1) subunit and profoundly affects multiple channel properties
      such as voltage-dependent activation, inactivation rates, G-protein modulation,
      drug sensitivity and cell surface expression. Here, we report the high-resolution
      crystal structures of the Ca(V)beta2a conserved core, alone and in complex with
      the AID. Previous work suggested that a conserved region, the beta-interaction
      domain (BID), formed the AID-binding site; however, this region is largely buried
      in the Ca(V)beta core and is unavailable for protein-protein interactions. The
      structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages
      the AID through an extensive, conserved hydrophobic cleft (named the alpha
      binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta
      near the intracellular end of a pore-lining segment, called IS6, that has a
      critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas
      influence Ca(V) gating by direct modulation of IS6 movement within the channel
      pore.

PMID- 15141231
TI  - Another good reason to floss.

PMID- 15141232
TI  - Baby mice develop human immune systems.

PMID- 15141235
TI  - NIOSH publishes occupational safety and health resources.

PMID- 15141239
TI  - Animal use for in vitro work: how much justification is enough?

PMID- 15141241
TI  - What's your diagnosis? Abdominal mass with abdominal hernia.

PMID- 15141243
TI  - A conversation with Fernando Nottebohm, PhD. Interviewed by Michael Eisenstein.
AB  - During the last 30 years, a number of revolutionary discoveries in the field of
      neuroscience have come from what was, at first, an unexpected direction: songbird
      research. Investigations into seasonal and sex-specific differences in birdsong
      development have led to important revelations about the impact of sex hormones on
      brain development and the hormonally controlled plasticity of brain structure, as
      well as the particularly surprising discovery that neurogenesis continues to
      occur in the adult brain (see Harding, p. 28). The work of Fernando Nottebohm is
      widely recognized as having played a key role in bringing these findings to light
      and thus forcing a general re-examination of established principles of
      neuroscience. Fernando Nottebohm is Dorothea L. Leonhardt Distinguished Professor
      at The Rockefeller University, and Director of The Rockefeller Field Research
      Center for Ethology and Ecology, a 1,200-acre facility located in Millbrook, NY,
      that provides researchers the opportunity to study behavior and brain function
      under natural conditions. Nottebohm's pioneering work on the neural control of
      birdsong has led to major discoveries with large impacts in the fields of animal
      behavior and neuroscience, and has made him one of the founders of neuroethology,
      the study of how the nervous system controls animal behavior. Nottebohm is a
      Member of the National Academy of Sciences, USA, and a Fellow of the American
      Association for the Advancement of Science and of the American Academy of Arts
      and Sciences. We had a chance to sit down with him to discuss his distinguished
      career working with laboratory birds.

PMID- 15141244
TI  - Learning from bird brains: how the study of songbird brains revolutionized
      neuroscience.
AB  - During the past 30 years, songbirds have become a popular model for neuroscience
      research. The author reviews three fundamental discoveries that have
      revolutionized the field and changed the way we understand the structure and
      function of the brain.

PMID- 15141245
TI  - Lack of efficacy of injectable ketamine with xylazine or diazepam for anesthesia
      in chickens.
AB  - Compared to other laboratory animals, little is known about the use of
      anesthetics in birds, potentially resulting in the use of improper dosing
      regimens. The authors compared two commonly used ketamine combinations with
      isoflurane and concluded that the injectable doses were ineffective for induction
      of surgical anesthesia in chickens.

PMID- 15141246
TI  - The evolution of birds: an overview of the avian tree of life.
AB  - The author provides a general overview of the molecular data used to reconstruct
      the avian tree of life, summarizes some highlights of the ensuing controversies,
      and reveals those taxonomic relationships that remain largely unchanged by
      molecular data.

PMID- 15141248
TI  - A neuron is worth a thousand words.

PMID- 15141252
TI  - HHS creates new advisory board to improve biosecurity in "dual use" research.

PMID- 15141249
TI  - The sweet smell of successful cloning.

PMID- 15141254
TI  - Virtual IACUC meetings: compliant or not?

PMID- 15141259
TI  - What's your diagnosis? Filariasis.

PMID- 15141261
TI  - Leaders in laboratory animal science: in their own words.
AB  - There are a number of challenges facing young people planning their future with
      little but a love of animals to guide them. Pursuing a successful career in
      veterinary medicine can be a trying experience; there are a limited number of
      highly competitive academic programs, and even if one manages to enroll in such a
      program and complete the degree, there remains the daunting dilemma of whether to
      proceed directly to private practice, or whether instead to strike out on a new
      path and explore an alternative career in animal medicine. The eleven men and
      women profiled here are all respected figures from the laboratory animal science
      community, representing a broad cross-section of backgrounds and interests:
      genetics researchers, exotic species specialists, animal welfare advocates,
      nutritionists, facility managers, and so forth. Some worked their way through
      veterinary school and private practice before deciding on a radical career shift
      that brought them to where they are now, others started their careers in a
      laboratory, while others still followed a more indirect path, guided only by
      chance, curiosity, and a love of animals.All eleven, however, have each made
      their own unique contribution to the field, and Lab Animal has invited them to
      tell their own stories, in their own words, to illustrate some of the
      interesting, entertaining, and surprising turns a career in laboratory animal
      science can take.

PMID- 15141262
TI  - Creating a comprehensive training documentation program.
AB  - The regulations mandate that individuals involved in research animal care and use
      receive adequate training, but they fail to address the documentation of the
      training. The authors provide guidelines for training documentation and, as an
      example, describe the program in place at the University of Pennsylvania.

PMID- 15141263
TI  - Prophylactic acetaminophen does not prevent epidural fever in nulliparous women:
      a double-blind placebo-controlled trial.
AB  - OBJECTIVE: Epidural analgesia is associated with a four- to five- fold increase
      in noninfectious maternal fever in nulliparous women. Fever prophylaxis may
      safely reduce both unnecessary neonatal sepsis evaluations and the potential
      effect of fever on the fetus. STUDY DESIGN: We performed a randomized double
      blind placebo-controlled study. Immediately after epidural placement, full-term
      nulliparas with a temperature of <99.5 degrees F received acetaminophen 650 mg or
      placebo, per rectum, every 4 hours. Tympanic membrane temperatures were measured
      hourly. Our power to detect an effect of acetaminophen treatment on maternal
      temperature over time was 90%. RESULTS: In all, 21 subjects were randomized to
      each arm. Treatment with acetaminophen did not impact maternal temperature
      curves. Fever >100.4 degrees F was identical in the acetaminophen and placebo
      groups (23.8%, p=1.0). Neonatal surveillance blood cultures did not reveal occult
      infection. CONCLUSIONS: Acetaminophen prophylaxis prevented neither maternal
      hyperthermia nor fever secondary to epidural analgesia, suggesting that the
      mechanism underlying fever does not include centrally mediated perturbations of
      maternal thermoregulation.

PMID- 15141264
TI  - The histologic fetoplacental inflammatory response in fatal perinatal group B
      streptococcus infection.
AB  - OBJECTIVE: To determine the rate of histologic fetoplacental inflammation in
      fetuses and newborns with fatal perinatal Group B-Streptococcus (GBS) infection.
      STUDY DESIGN: Autopsy files (1990 to 2002) were searched for fetuses and newborns
      with GBS-positive post-mortem blood and/or lung cultures. The rate of
      histological fetoplacental inflammation in preterm (< 36 weeks gestational age)
      and term (> or =36 weeks) fetuses/infants was compared using chi(2) test.
      RESULTS: GBS infection was diagnosed in 4.9% (61/1236) of perinatal autopsies and
      was considered the exclusive cause of death in 58 cases (16 to 41 weeks
      gestation, median: 26 weeks). A total of 43 fetuses/infants (74%) were preterm,
      24 (41%) were male and 33 (57%) stillborn. The histologic fetoplacental
      inflammatory response was age-dependent for the following variables: acute
      chorioamnionitis (seen in 67% of preterm vs 33% of term fetuses/infants, p <
      0.05), multiple-vessel umbilical vasculitis (37 vs 7%, p < 0.05), funisitis (37
      vs 13%, p < 0.05), and the presence of neutrophils in the gastrointestinal tract
      (35% vs none, p < 0.05). Neutrophils in the pulmonary airspaces (47 vs 33%) and
      pneumonia (16 vs 27%) were found with similar frequency in both groups.
      CONCLUSION: Histologic fetoplacental inflammation is a poor indicator of
      perinatal GBS infection; the sensitivity is 67% in preterm and 33% in term
      fetuses/newborns (overall sensitivity 59%). The higher rate of histologic
      inflammation in preterm fetuses/newborns suggests age-specific interactions
      between microorganism, host and placenta.

PMID- 15141265
TI  - A prospective observational pilot study of synchronized nasal intermittent
      positive pressure ventilation (SNIPPV) as a primary mode of ventilation in
      infants > or = 28 weeks with respiratory distress syndrome (RDS).
AB  - OBJECTIVE: To compare the outcome of infants with respiratory distress syndrome
      (RDS) in the neonatal intensive care unit (NICU) who were extubated to
      synchronized nasal intermittent positive pressure ventilation (SNIPPV) or
      continued on conventional ventilation (CV), immediately postsurfactant. STUDY
      DESIGN: Prospective observational study of postsurfactant ventilatory management
      of consecutive infants (born between 10/99 and 12/02) of 28 to 34 weeks
      gestation. Extubation to SNIPPV was at the attending neonatologists' discretion.
      Babies in the CV group remained intubated, postsurfactant. RESULTS: There were no
      significant differences in the maternal demographics, antenatal steroid use, mode
      of delivery, birth weight (BW), gestational age (GA), gender, Apgar at 5 minutes,
      age at surfactant instillation, or oxygenation index (OI) prior to surfactant
      administration, between infants continued on CV (n=35) and those extubated to
      SNIPPV (n=24). The total duration of endotracheal intubation (mean+/-SEM; CV
      versus SNIPPV; 2.4+/-0.4 versus 0.3+/-0.0 days, p=0.001) and duration of
      supplemental oxygen exposure (15+/-3.2 versus 8.2+/-3.3 days, p=0.04) were
      significantly shorter in the SNIPPV group. Furthermore, the duration of
      parenteral nutrition (12.1+/-1.6 versus 8.4+/-0.8 days, p=0.02) and length of
      stay (37.5+/-3.0 versus 29.1+/-3.3 days, p=0.04) were also significantly shorter
      in the SNIPPV group. There were no differences between the two groups in blood
      gas or OI values postsurfactant (up to 48 hours). There was no statistical
      difference in the incidence of intraventricular hemorrhage grade I (three (9%) in
      the CV group and two infants (8%) in the SNIPPV group). No infant died in either
      group or had patent ductus arteriosus, air leaks, necrotizing enterocolitis,
      periventricular leukomalacia, retinopathy of prematurity or bronchopulmonary
      dysplasia. CONCLUSIONS: Infants of 28 to 34 weeks GA with RDS requiring
      surfactant with early extubation to SNIPPV had a shorter duration of intubation,
      and decreased need for oxygen as compared to CV. There was also a significant
      decrease in the duration of parenteral nutrition and hospitalization. SNIPPV is a
      safe and effective primary mode of ventilation in larger premature infants.

PMID- 15141266
TI  - Working together in the neonatal intensive care unit: provider perspectives.
AB  - OBJECTIVES: To elicit healthcare provider perceptions of working together in a
      neonatal intensive care unit (NICU). STUDY DESIGN: We conducted focus groups to
      elicit descriptions of how providers work together. The groups included one each
      of transport nurses, staff nurses, residents, fellows, attending physicians and
      two multiple provider groups. To identify themes and their descriptive elements
      we performed qualitative data analysis. RESULTS: There were three to seven
      participants per group for a total sample of 36. Provider responses to questions
      about working together centered around three major themes: (1) Provider
      Characteristics; (2) Workplace Factors and; (3) Group Influences. Provider
      Characteristics were defined by personal attributes, reputation, and expertise.
      Workplace Factors included staffing, work organization, and work environment.
      Group Influences were described by communication and relationships. CONCLUSIONS:
      Providers in this NICU described three broad organizational and interpersonal
      factors that influence how they work together, yet no consistent descriptions of
      teams or teamwork were found. The organizational factors, often far removed from
      bedside, should be considered when evaluating how providers work together.

PMID- 15141267
TI  - Intrauterine growth restriction impacts tolerance to total parenteral nutrition
      in extremely low birth weight infants.
AB  - BACKGROUND: Hepatobiliary dysfunction is well recognized as a complication of
      long-term total parenteral nutrition (TPN). Because intrauterine growth
      restriction (IUGR) alters a number of metabolic and physiologic variables in the
      fetus that probably affect the hepatocyte function and tolerance to feedings in
      the IUGR extremely low birth weight (ELBW), we hypothesized that this group of
      babies would have an increased incidence of TPN-associated cholestasis and
      chronic liver failure. METHODS: We performed a review of all ELBW infants (birth
      weight <1000 g) that received TPN for >7 days. RESULTS: Among 1768 infants
      admitted to the neonatal intensive care unit there were 103 ELBW who received TPN
      >7 days, 38 (37%) of them developed TPN cholestasis. Among 69 appropriate for
      gestational age (AGA)-ELBW infants, 19 (27%) developed cholestasis compared to
      19/34 small for gestational age (SGA)-ELBW infants (56%) (p<0.0009). Maximum
      direct bilirubin values and days on TPN were similar in both groups. SGA-ELBW
      infants had an increased incidence and earlier onset of cholestasis when compared
      to AGA-ELBW patients. Liver biopsies and/or autopsies of infants that developed
      liver failure (four AGA/four SGA) showed extensive sinusoidal/portal fibrosis
      compatible with "TPN lesion". In the other 30 cases, liver function eventually
      returned to normal after TPN discontinuation. CONCLUSIONS: When compared, SGA
      ELBW infants who received TPN >7 days, despite being more mature than AGA-ELBW
      infants, have an increased risk for TPN cholestasis and developed this
      complication earlier in life. However, the incidence of chronic liver failure was
      not different in these two groups.

PMID- 15141268
TI  - Clinical and economic outcomes of preterm labor management: inpatient vs
      outpatient.
AB  - OBJECTIVE: To compare pregnancy and economic outcomes in women receiving
      inpatient vs outpatient tocolysis with continuous subcutaneous terbutaline (SQT).
      STUDY DESIGN: Identified within a database were women prescribed SQT at 24.0 to
      33.9 weeks' gestation following stabilization of an acute episode of preterm
      labor. Women with cervical dilatation >3 cm, and/or maternal or fetal instability
      were excluded. Those with prolonged inpatient care were matched 1:1 to those
      discharged with outpatient follow-up by cervical dilatation, gestational age, and
      fetal number yielding 90 matched pairs (180 women). RESULTS: Inpatients had an
      earlier gestational age at delivery (34.1+/-2.9 vs 35.8+/-1.9 weeks, p<0.001),
      higher preterm birth rate (86.7% vs 74.4%, p=0.043) and higher overall costs
      (56,089 dollars+/-47,944 dollars vs 25,540 dollars+/-25,847 dollars, p<0.001)
      than outpatients. CONCLUSION: Outpatient management resulted in improved
      pregnancy outcomes at a cost less than that of inpatient management in this
      analysis of women treated with SQT.

PMID- 15141269
TI  - Gamma-glutamyltransferase: an effect modifier in the association between age and
      hypertension in a 4-year follow-up study.
AB  - We performed a prospective study to assess whether the relationship of age with
      hypertension was stronger in men with high normal serum gamma glutamyltransferase
      (GGT) than in those with lower GGT levels. The study population included 8170
      healthy male workers in a steel manufacturing company who had undergone health
      examinations in both 1994 and 1998. The higher the baseline GGT level, the effect
      of age on the development of hypertension was stronger. The incidence of
      hypertension among those aged 25-34, 35-44 and 45-50 years was 0.9, 2.2, 3.8% in
      those with GGT<20 U/l; 1.0, 4.1, 12.5% in those with GGT between 20 and 39 U/l;
      and 1.9, 6.3, 17.2% in those with GGT> or =40 U/l, respectively. All
      relationships persisted after adjusting for baseline values of body mass index,
      alcohol intake, smoking, exercise, family history of hypertension, systolic and
      diastolic blood pressure, and changes of body mass index during 4 years (P for
      interaction=0.03). Our data supported the hypothesis that the effect of age on
      the development of hypertension differed by baseline GGT level, although the
      underlying mechanism for this interaction is unclear.

PMID- 15141270
TI  - Influence of the presence of doctors-in-training on the blood pressure of
      patients: a randomised controlled trial in 22 teaching practices.
AB  - Until now, no information is available about the effect of the presence of a
      doctor-in-training on a patient's blood pressure. We tested the hypothesis that
      the presence of a last year medical student might increase the blood pressure of
      the patient, in addition to the possible pressor response to the doctor-trainer.
      Normotensive and hypertensive patients with a minimum age of 25 years, visiting
      for any reason, were recruited at 22 teaching general practices. Patients were
      randomised into a 'trainee' group (n=133) and a 'no trainee' (n=129) group. The
      blood pressure was measured at two subsequent contacts. In the 'trainee' group, a
      student was present at the first visit only. In the 'no trainee' group, both
      visits were without student. Both groups had similar anthropometric
      characteristics at entry. At the first visit, systolic pressure was higher in the
      'trainee' group than in the control group (139.5 vs 133.1 mmHg, P=0.004), with a
      similar trend for diastolic pressure (80.2 vs 77.8 mmHg, P=0.07). From the first
      contact to the follow-up visit, blood pressure decreased in the trainee group by
      4.8 mmHg systolic (P<0.001) and 1.7 mmHg diastolic (P=0.03), whereas the
      corresponding changes in the control group were -0.1 mmHg (P=0.90) and +1.5 mmHg
      (P=0.03). Thus, the between group differences in these trends averaging 4.7 mmHg
      (CI 1.5-7.9, P=0.005) systolic and 3.2 mmHg (CI 1.1-5.3, P=0.003) diastolic were
      statistically significant. We conclude that in teaching-practices, the presence
      of a doctor-in-training has a significant pressor effect when an experienced
      general practitioner measures a patient's blood pressure. If confirmed, our
      findings imply that doctors should be cautious to initiate or adjust
      antihypertensive treatment when blood pressure readings are obtained in the
      presence of a student.

PMID- 15141271
TI  - Detection of Vibrio parahaemolyticus and Vibrio cholerae in oyster, Crassostrea
      rhizophorae, collected from a natural nursery in the Coco river estuary,
      Fortaleza, Ceara, Brazil.
AB  - Oysters are edible organisms that are often ingested partially cooked or even
      raw, presenting therefore a very high risk to the consumers' health, especially
      in tropical regions. The presence of Vibrio cholerae and Vibrio parahaemolyticus
      in oysters sampled at an estuary in the Brazilian northeastern region was
      studied, with 300 oysters tested through an 8-months period. The salinity of the
      water at the sampling point varied between 3% and 27. V. cholerae was the most
      frequently detected species (33.3% of the samples), and of the 22 V. cholerae
      isolates, 20 were identified as non-O1/non-O139, with two of the colonies
      presenting a rough surface and most of remaining ones belonging to the Heiberg II
      fermentation group. V. parahaemolyticus was isolated from just one of the
      samples. Other bacteria such as Providencia spp., Klebsiella spp. and Morganella
      morganii were also isolated.

PMID- 15141272
TI  - Impact of antihelminthic treatment on infection by Ascaris lumbricoides,
      Trichuris trichiura and hookworms in Covas, a rural community of Pernambuco,
      Brazil.
AB  - This work aims to evaluate the impact of drug treatment on infection by Ascaris
      lumbricoides (Al), Trichuris trichiura (Tt) and hookworms (Hook) in a rural
      community from the sugar-cane zone of Pernambuco, Brazil. Four parasitological
      surveys were carried out from March 2001 to March 2002. Individual diagnosis was
      based on eight slides (four by the Kato-Katz method and four by the Hoffman
      method) per survey. Infected subjects were assigned to two groups for treatment
      with either albendazole (n = 62) or mebendazole (n = 57). Prevalence of infection
      fell significantly (p < 0.05) one month after treatment: Al (from 47.7% to 6.6%);
      Tt (from 45.7% to 31.8%) and Hook (from 47.7% to 24.5%). One year after
      treatment, infections by Tt and Hook remained significantly below pre-control
      levels. A substantial decrease in single-infection cases and multiple infections
      was found. Egg-negative rate was significant for Al (94.0%), Hook (68.3%) but not
      for Tt (45.5%), and did not differ significantly between subjects treated with
      mebendazole or albendazole. Egg counts fell significantly in the individuals
      remaining positive for Tt. It is recommended that antihelminthic treatment should
      be selective and given at yearly intervals preferably with albendazole, due to
      its cost-effectiveness.

PMID- 15141273
TI  - Treatment with mebendazole is not associated with distal migration of adult
      Angiostrongylus costaricensis in the murine experimental infection.
AB  - Abdominal angiostrongyliasis is a zoonotic infection produced by a metastrongylid
      intra-arterial nematode, Angiostrongylus costaricensis. Human accidental
      infection may result in abdominal lesions and treatment with anti-helminthics is
      contra-indicated because of potential higher morbidity with excitement or death
      of worms inside vessels. To evaluate the effect of mebendazole on localization of
      the worms, male Swiss mice, 5 week-old, were infected with 10 third stage larvae
      per animal. Twelve infected mice were treated with oral mebendazol, at 5
      mg/kg/day, for 5 consecutive days, begining 22 days after inoculation. As control
      groups, 12 infected but non-treated mice and other 12 non-infected and non
      treated mice were studied. The findings at necropsy were, respectively for the
      treated (T) and control (C) groups: 92% and 80% of the worms were inside the
      cecal mesenteric arterial branch; 8% and 10% were located inside the aorta. Only
      in the group C some worms (10%) were found inside the portal vein or splenic
      artery. These data indicate that treatment with mebendazole does not lead to
      distal or ectopic migration of A. costaricensis worms.

PMID- 15141275
TI  - Study of enteroparasites infection frequency and chemotherapeutic agents used in
      pediatric patients in a community living in Porto Alegre, RS, Brazil.
AB  - Parasitic infections caused by intestinal protozoan and helminths affect more
      than two billion people worldwide and chemotherapy is the most commonly used
      therapeutic procedure. Considering the problems created by parasitic infections
      and the incorrect use of drugs, the aim of this work was to detect the frequency
      of enteroparasites infection and to estimate the use of chemotherapeutic agents
      in children living in the periphery of the city of Porto Alegre, RS, Brazil.
      Ninety-six preschool age children, who had parasitological exams and who used
      antiparasitic drugs, were analyzed. The efficacy of treatment was evaluated by
      stool examination repeated six months after treatment. The same diagnostic test
      was used to evaluate parasitological cure, which was defined as absence of eggs
      and cysts in the stool. From these children, 79 (82.3%) were contaminated by some
      species of parasite, the most prevalent were Ascaris lumbricoides, Trichuris
      trichiura and Giardia lamblia. The most commonly used drugs were mebendazole (86%
      of prescriptions) and metronidazole (30.3%). The cure rate in the 79 children,
      examined 6 months after treatment, was 65.3% for A. lumbricoides and 66.1% for T.
      trichiura. This study suggests that a continuous education program regarding the
      prevention and treatment of parasitic infections is an essential tool for their
      eradication.

PMID- 15141276
TI  - Human toxocariasis: frequency of anti-Toxocara antibodies in children and
      adolescents from an outpatient clinic for lymphatic filariasis in Recife,
      Northeast Brazil.
AB  - In a transversal study on a sample of 386 children and adolescents from an
      outpatient clinic for filariasis in Recife, Northeast Brazil, the frequency of
      anti-Toxocara antibodies and its relation to age, gender, number of peripheral
      eosinophils, Wuchereria bancrofti microfilariae and intestinal helminths was
      determined. The total anti-Toxocara IgG antibody frequency was 39.4%, by ELISA
      technique. The difference in frequency between males (40.1%) and females (37.6%)
      was not statistically significant. The 6 to 10-year-old subset presented the
      highest frequency of anti-Toxocara antibodies (60%), and within this age group
      there was a statistically significant male bias. There was also a significant
      association between the number of eosinophils and the presence of anti-Toxocara
      antibodies. Intestinal parasite frequency was 52.1%, but no association was found
      between this data and the presence of anti-Toxocara antibodies. In the present
      sample, 42.2% of the patients were Wuchereria bancrofti carriers, however, again
      this was not associated with the presence of anti-Toxocara antibodies. In
      conclusion, anti-Toxocara antibodies were highly prevalent in this sample. The
      present data show that there is no cross correlation between anti-Toxocara IgG
      antibody and the presence of intestinal helminths and filariasis.

PMID- 15141278
TI  - Determination of human cytomegalovirus genetic diversity in different patient
      populations in Costa Rica.
AB  - Seroprevalence of HCMV in Costa Rica is greater than 95% in adults; primary
      infections occur early in life and is the most frequent congenital infection in
      newborns. The objectives of this study were to determine the genetic variability
      and genotypes of HCMV gB gene in Costa Rica. Samples were collected from
      alcoholics, pregnant women, blood donors, AIDS patients, hematology-oncology (HO)
      children and HCMV isolates from neonates with cytomegalic inclusion disease. A
      semi-nested PCR system was used to obtain a product of 293-296 bp of the gB gene
      to be analyzed by Single Stranded Conformational Polymorphism (SSCP) and
      sequencing to determine the genetic polymorphic pattern and genotypes,
      respectively. AIDS patients showed the highest polymorphic diversity with 14
      different patterns while fifty-six percent of HO children samples showed the same
      polymorphic pattern, suggesting in this group a possible nosocomial infection. In
      neonates three genotypes (gB1, gB2 and gB3), were determined while AIDS patients
      and blood donors only showed one (gB2). Of all samples analyzed only genotypes
      gB1, 2 and 3 were determined, genotype gB2 was the most frequent (73%) and mixed
      infections were not detected. The results of the study indicate that SSCP could
      be an important tool to detect HCMV intra-hospital infections and suggests a need
      to include additional study populations to better determine the genotype
      diversity and prevalence.

PMID- 15141279
TI  - Childhood astrovirus-associated diarrhea in the ambulatory setting in a Public
      Hospital in Cordoba city, Argentina.
AB  - Human astroviruses have been increasingly identified as important agents of
      diarrheal disease in children. However, the disease burden of astrovirus
      infection is still incompletely assessed. This paper reports results on the
      epidemiological and clinical characteristics of astrovirus-associated diarrhea,
      as well as the impact of astrovirus infection on the ambulatory setting at a
      Public Hospital in Cordoba city, Argentina. From February 2001 through January
      2002, 97 randomly selected outpatient visits for diarrhea among children < 36
      months old were enrolled. A single specimen of stool from each child was
      collected and tested for astrovirus antigen by enzyme immunoassay. Astroviruses
      were detected in 12.37% of the diarrheal episodes. All the positive cases
      occurred in children 4 to 18 months, but the highest rate was in children aged 4
      to 6 months (23.80%). The clinical symptoms of astrovirus associated-diarrhea
      were fever 41.66%, vomiting 25.00% and dehydration 8.33%; overall 16.66% required
      hospitalization. Astrovirus was identified through the year and no seasonally
      pattern was detected (cool semester 15.21% versus warm semester 9.80% p > 0.05).
      According to our estimation about one out of seventy-four children in this cohort
      would be assisted annually for an astroviral-diarrheal episode in the Public
      Hospital and one out of eight diarrheal cases could be attributed to astrovirus
      infection. Astrovirus is a common symptomatic infection in pediatric outpatient
      visits in the public hospital in the study area, contributing 12.37% of the
      overall morbidity from diarrhea.

PMID- 15141280
TI  - Effects of eucalyptol on house fly (Diptera: Muscidae) and blow fly (Diptera:
      Calliphoridae).
AB  - The effects of eucalyptol were evaluated against the house fly, Musca domestica
      L., and blow fly, Chrysomya megacephala (F.). The bioassay of adults, using
      topical application, indicated that M. domestica males were more susceptible than
      females, with the LD50 being 118 and 177 microg/fly, respectively. A higher LD50
      of C. megacephala was obtained; 197 microg/fly for males and 221 microg/fly for
      females. Living flies of both species yielded a shorter life span after being
      treated with eucalyptol. The bioassay of larvae, using the dipping method on the
      third instar, showed that M. domestica was more susceptible than C. megacephala,
      with their LC50 being 101 and 642 microg/microl, respectively. The emergence of
      adults, which had been treated with eucalyptol in larvae, decreased only in M.
      domestica. Having the volatile property, fumigation or impregnated paper test of
      eucalyptol or the efficacy of repellence or attractiveness merits further
      investigations to enhance bio-insecticidal efficacy.

PMID- 15141282
TI  - Immunogenicity of three recombinant hepatitis B vaccines administered to students
      in three doses containing half the antigen amount routinely used for adult
      vaccination.
AB  - We evaluated the immunogenicity of three recombinant hepatitis B vaccines, one
      Brazilian (Butang, Instituto Butantan) and two Korean vaccines (Euvax-B, LG
      Chemical Ltd. and Hepavax-Gene, Greencross Vaccine Corp.), administered
      intramuscularly to students aged 17 to 19 years in three 10- micro g doses
      (corresponding to half the amount of antigen routinely used for adult
      vaccination) at intervals of one month between the first and second dose, and of
      four months between the second and third dose. A total of 316 students non
      reactive for any serological marker of hepatitis B virus infection were
      vaccinated: 77 (24.4%) with the Butang vaccine, 71 (22.5%) with Euvax-B, 85
      (26.9%) with Hepavax-Gene and, for comparison, 83 (26.2%) with Engerix-B
      (GlaxoSmithKline), whose efficacy in young adults at the dose used here has been
      confirmed in previous studies. Similar seroconversion rates (anti-HBs > 10 mIU/mL
      about one month after application of the third dose) were obtained for the
      Butang, Euvax-B, Hepavax-Gene and Engerix-B vaccines (96.2%, 98.6%, 96.5% and
      97.6%, respectively). The frequency of good responders (anti-HBs > 100 mIU/mL)
      was also similar among students receiving the four vaccines (85.8%, 91.6%, 89.4%
      and 89.2%, respectively). The geometric mean titers (GMT) of anti-HBs about one
      month after the third dose obtained with these vaccines were 727.78 +/- 6.46
      mIU/mL, 2009.09 +/- 7.16 mIU/mL, 1729.82 +/- 8.85 mIU/mL and 2070.14 +/- 11.69
      mIU/mL, respectively. The GMT of anti-HBs induced by the Euvax-B and Engerix-B
      vaccines were higher than those obtained with the Butang vaccine (p < 0.05); this
      difference was not significant when comparing the other vaccines two-by-two. No
      spontaneous adverse effects attributable to the application of any dose of the
      four vaccines were reported.

PMID- 15141283
TI  - Mapping of a Leishmania major gene/locus that confers pentamidine resistance by
      deletion and insertion of transposable element.
AB  - Pentamidine (PEN) is an alternative compound to treat antimony-resistant
      leishmaniasis patients, which cellular target remains unclear. One approach to
      the identification of prospective targets is to identify genes able to mediate
      PEN resistance following overexpression. Starting from a genomic library of
      transfected parasites bearing a multicopy episomal cosmid vector containing wild
      type Leishmania major DNA, we isolated one locus capable to render PEN resistance
      to wild type cells after DNA transfection. In order to map this Leishmania locus,
      cosmid insert was deleted by two successive sets of partial digestion with
      restriction enzymes, followed by transfection into wild type cells,
      overexpression, induction and functional tests in the presence of PEN. To
      determine the Leishmania gene related to PEN resistance, nucleotide sequencing
      experiments were done through insertion of the transposon Mariner element of
      Drosophila melanogaster (mosK) into the deleted insert to work as primer island.
      Using general molecular techniques, we described here this method that permits a
      quickly identification of a functional gene facilitating nucleotide sequence
      experiments from large DNA fragments. Followed experiments revealed the presence
      of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has
      now been analyzed.

PMID- 15141284
TI  - The frequency rate of Toxocara species contamination in soil samples from public
      yards in a urban area "Payathai", Bangkok, Thailand.
AB  - Toxocara species are most common roundworms of Canidae and Felidae. Human
      toxocariasis develops by ingesting of embryonated eggs in contaminated soil.
      There is no previous report of Toxocara contamination in the soil samples from
      the public areas in Bangkok. For this reason our study have been carried out to
      examine the frequency of Toxocara eggs in public yards in Bangkok, Thailand. A
      total of 175 sand and clay samples were collected and examined for parasite eggs.
      According to this study, Toxocara eggs were detected from 10 (5.71%) of 175 soil
      samples. The high rate of contamination in this study implies the importance of
      the control of this possible zoonotic disease: control of abandon of dogs and
      cats, is still necessary.

PMID- 15141285
TI  - "Multiplex PCR" identification of the atypical and monophasic Salmonella enterica
      subsp. enterica serotype 1,4,[5],12:i:- in Sao Paulo State, Brazil: frequency and
      antibiotic resistance patterns.
AB  - Salmonella spp. are the etiologic agents of salmonellosis, a worldwide spread
      zoonoses causing foodborne outbreaks and clinical diseases. By serological
      identification, Salmonella enterica subsp. enterica serotype 1,4,[5],12:i:-
      accounted for 8.8% of human and 1.6% of nonhuman Salmonella strains isolated in
      Sao Paulo State, during 1991-2000. A total of 28.6% of them amplified a fragment
      corresponding to H:1,2 (flagellar phase two) through PCR analysis and were
      further assigned as S. Typhimurium. Antimicrobial resistance was detected in
      36.3% of the 369 PCR-negative strains tested, including the multiresistance to
      ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin.

PMID- 15141286
TI  - REF: The biological meaning of anti-HBc positive result in blood donors: relation
      to HBV-DNA and to other serological markers.

PMID- 15141287
TI  - Formic acid excretion in rats and mice exposed to bromodichloromethane: a
      possible link to renal tubule cell proliferation in long-term studies.
AB  - Male F344 rats exposed to bromodichloromethane (BDCM) by gavage at 50 or 100
      mg/kg/day for 5 days a week for 28 days excreted large amounts of formic acid in
      their urine, which was accompanied by a change in urinary pH. Male B6C3F1 mice
      exposed to BDCM at 25 or 50 mg/kg/day for 5 days a week for 28 days also excreted
      increased amounts of formic acid in their urine. In rats, formate excretion was
      dose and time dependant, being markedly elevated after four doses and remaining
      at that level after 3 weeks of dosing at 100 mg/kg/day BDCM, while at 50
      mg/kg/day there was some suggestion of a decline after 3 weeks. In contrast, in
      mice formate excretion did not start to a major extent until 3 weeks of dosing,
      with the biggest response at 4 weeks. There was no increase in clinical chemistry
      markers of liver or kidney injury in either rats or mice following 28-day
      exposure to BDCM. However, morphological examination of the kidneys showed some
      mild renal tubule injury in two out of five rats exposed to 100 mg/kg/day BDCM.
      This was associated with a marked increase in cell proliferation in the renal
      cortex of all rats exposed to 100 mg/kg/day. No increase in cell proliferation
      was seen in the renal cortex of rats exposed to BDCM at 50 mg/kg/day, or in mice
      exposed to 25 or 50 mg/kg/day BDCM for 28 days. Long-term exposure to formic acid
      is known to cause kidney damage, suggesting that excretion of this acid may be a
      contributory factor to the increase in cell proliferation and kidney damage seen
      in the longer-term studies with BDCM.

PMID- 15141289
TI  - Peter Sjokvist.

PMID- 15141290
TI  - Variation of infected cell count in bronchoalveolar lavage and timing of
      ventilator-associated pneumonia.
AB  - OBJECTIVES: The aim of this study was to evaluate and compare the accuracy of the
      percentage of infected cells (%IC) in bronchoalveolar lavage (BAL) for ventilator
      associated pneumonia (VAP) diagnosis according to its onset from the initiation
      of mechanical ventilation. PATIENTS: One hundred and eight patients admitted to a
      surgical ICU were retrospectively included (1999-2001). A total of 171 cases of
      VAP were diagnosed on clinical, biological, chest X-ray and BAL results
      (threshold >/=10(4 )cfu/ml). RESULTS: The %IC significantly decreased with the
      timing of VAP diagnosis: 12.2+/-12.1% for VAP occurring less than 7 days after
      the initiation of mechanical ventilation, 7.4+/-9.2% for VAP occurring between 7
      and 15 days and 4.8+/-6.4% for VAP after 15 days ( p=0.0002), despite the same
      number of elements and proportion of polymorphonuclear neutrophils in BAL. In
      addition, a relationship between the %IC and the pathogen responsible for VAP was
      observed for P. aeruginosa [higher for VAP <7 days than for VAP 7-15 days (
      p=0.01) and VAP >15 days ( p=0.006)] and S. aureus [lower for VAP >15 days than
      VAP 7-15 days ( p=0.04) and VAP <7 days ( p=0.04)]. Furthermore, the %IC in BAL
      was lower in patients undergoing antimicrobial therapy than in patients without
      antibiotics ( p=0.04). Three factors were independently associated with the %IC:
      quantitative culture of BAL (beta=0.42, p<0.0001), ongoing antimicrobial therapy
      (beta= -0.21, p=0.003) and onset of VAP (beta= -0.17, p=0.01). CONCLUSIONS: A
      relationship between the %IC in BAL, duration of ventilation, quantitative
      culture of BAL and ongoing antimicrobial therapy has been proved in this study.
      The %IC for VAP diagnosis may not be accurate in patients with ongoing
      antibiotics and late onset infections (>7 days).

PMID- 15141291
TI  - Looking at subgroups in an inhomogeneous population does not make these subgroups
      more homogeneous.

PMID- 15141292
TI  - Comparative genetic analysis of quantitative traits in sunflower (Helianthus
      annuus L.) 3. Characterisation of QTL involved in resistance to Sclerotinia
      sclerotiorum and Phoma macdonaldi.
AB  - One hundred and fifty F(2)-F(3) families from a cross between two inbred
      sunflower lines FU and PAZ2 were used to map quantitative trait loci (QTL) for
      resistance to white rot (Sclerotinia sclerotiorum) attacks of terminal buds and
      capitula, and black stem ( Phoma macdonaldii). A genetic linkage map of 18
      linkage groups with 216 molecular markers spanning 1,937 cM was constructed.
      Disease resistances were measured in field experiments for S. sclerotiorum and
      under controlled conditions for P. macdonaldii. For resistance to S. sclerotiorum
      terminal bud attack, seven QTL were identified, each explaining less than 10% of
      phenotypic variance. For capitulum attack by this parasite, there were four QTL
      (each explaining up to 20% of variation) and for P. macdonaldii resistance, four
      QTL were identified, each having effects of up to 16%. The S. sclerotiorum
      capitulum resistance QTL were compared with those reported previously and it was
      concluded that resistance to this disease is governed by a considerable number of
      QTL, located on almost all the sunflower linkage groups.

PMID- 15141293
TI  - Use of Pi5(t) markers in marker-assisted selection to screen for cultivars with
      resistance to Magnaporthe grisea.
AB  - Identification of the PCR markers tightly linked to genes that encode important
      agronomic traits is useful for marker-assisted selection (MAS). The rice Pi5(t)
      locus confers broad-spectrum resistance to Magnaporthe grisea, the causal agent
      of rice blast disease. It has been hypothesized that the Pi5(t) locus carries the
      same gene as that encoded by the Pi3(t) and Pii(t) loci. We developed three PCR
      based dominant markers (JJ80-T3, JJ81-T3, and JJ113-T3) from three previously
      identified BIBAC clones-JJ80, JJ81, and JJ113-that are linked to the Pi5(t)
      locus. PCR analysis of 24 monogenic lines revealed that these markers are present
      only in lines that carry Pi5(t), Pi3(t), and Pii(t). PCR and DNA gel-blot
      analysis of candidate resistance lines using JJ80-T3, JJ81-T3, and JJ113-T3
      indicated that Tetep is the likely donor of Pi5(t). Of the 184 rice varieties
      tested, 34 carried the JJ80-T3-, JJ81-T3-, and JJ113-T3-specific bands. Disease
      evaluation of those 34 varieties revealed that all conferred resistance to PO6-6.
      The genomic structure of three of these resistant varieties (i.e., IR72, Taebaeg,
      Jahyangdo) is most similar to that of Pi5(t). Our results demonstrate the
      usefulness of the JJ80-T3, JJ81-T3, and JJ113-T3 markers for MAS for M. grisea
      resistance.

PMID- 15141295
TI  - [Hydroxyethyl starch-(HES)-induced pruritus as secondary complication of an
      occupational accident].
AB  - A 29-year old employee (controller in the textile industry) had an occupational
      accident leading to a femoral fracture. After surgery, he developed acute
      respiratory distress syndrome (ARDS) necessitating intensive care treatment.
      Three weeks after the accident, he developed generalized severe itching on a
      daily basis unresponsive to systemic and topical treatments. After one year, the
      itching had decreased to approximately 50% of its initial intensity. Hydroxyethyl
      starch (HES)-induced pruritus was diagnosed, based on the typical history and
      clinical features, the proven administration of HES and its cutaneous tissue
      storage by electron microscopy. Drug-induced pruritus caused by the plasma
      expander hydroxyethyl starch can be a secondary consequence of an occupational
      accident and thus an issue in accident compensation claims.

PMID- 15141296
TI  - [Results of overlapping sphincter repair in response to obstetric injury].
AB  - BACKGROUND: Obstetric trauma is one of the most common causes of faecal
      incontinence, and the standard therapy for clear sphincter defects is overlapping
      sphincter repair. We aimed to assess the short-term success rates of sphincter
      repair using modified V-Y plastic without covering colostomy and with primary
      closure of the perineum. METHODS: Between November 1997 and March 2002, 21
      patients were operated on for faecal incontinence due to obstetric trauma.
      Cleveland Clinic Incontinence Score (CCIS), patients' subjective assessment, and
      pathophysiological parameters were evaluated pre- and postoperatively. RESULTS:
      At follow-up, 19 patients (90%) reported improvements in continence symptoms over
      their preoperative situations. Three patients (14%) classified themselves
      subjectively as fully continent, six (28%) as highly improved, ten (48%) as
      improved, and two (10%) as unchanged. CONCLUSIONS: Our results indicate that
      faecal diversion is not necessary in sphincter repair and that primary perineal
      wound closure should be performed. Patients' subjective assessments and CCIS are
      suitable tools for evaluating improvements in faecal incontinence.

PMID- 15141297
TI  - [Foreign body-induced disruption of the gastrointestinal tract-anatomy of the
      ileocoecal opening].
AB  - INTRODUCTION: Over 75% of ingested foreign bodies pass the gastrointestinal tract
      without any complications. Blunt foreign bodies may lead to a disruption of the
      intestinal passage, mainly in the area of the ileocoecal opening. The size of the
      reported foreign bodies varies considerably. The aim of this study was the
      anatomic investigation to clarify the possible causes of obstruction and its
      influence on the diameter of the ileocoecal opening. MATERIAL AND METHOD: We
      investigate anatomically and describe the ileocoecal opening on the basis of 27
      specimens. RESULTS: We found not a flap mechanism but a valve mechanism in the
      ileocoecal junction. The median diameter of the formalin-fixated specimens was
      10.9 mm respectively 21.8 mm according to an assumed correction factor of 2. The
      cause for intestinal obstruction most probably is the ingestion of blunt, angular
      foreign bodies in the ostium ileale. CONCLUSION: The intraindividual differences
      as well as the considerable size of foreign bodies that pass the ileoceocal
      opening support the hypothesis, that the complications described are more a
      consequence of an ingestion of blunt, cornered foreign bodies in the ostium
      ileale independent ofn the size of the ileocoecal opening itself.

PMID- 15141298
TI  - [The myth of Prometheus mirrored in intensive medicine].

PMID- 15141300
TI  - Metabolism and signaling activities of nuclear lipids.
AB  - Apart from the lipids present in the nuclear envelope, the nucleus also contains
      lipids which are located further inside and are resistant to treatment with
      nonionic detergents. Evidence is being accumulated on the importance of internal
      nuclear lipid metabolism. Nuclear lipid metabolism gives rise to several lipid
      second messengers that function within the nucleus. Moreover, it is beginning to
      emerge that nuclear lipids not only act as precursors of bioactive second
      messengers but may be directly involved in regulation of nuclear structure and
      gene expression. Over the last 10 years, especially the role of the inositol
      lipid cycle in nuclear signal transduction has been extensively studied. This
      cycle is activated following a variety of stimuli and is regulated independently
      from the inositide cycle located at the plasma membrane. However, the nucleus
      contain other lipids, such as phosphatidylcholine, sphingomyelin, fatty acids and
      eicosanoids. There are numerous reports which suggest that these classes of
      nuclear lipids may play roles in the nucleus as important as those of
      phosphoinositides. This review aims at highlighting the most important aspects
      regarding the metabolism and signaling activities of nuclear phosphatidylcholine,
      sphingomyelin, fatty acids and eicosanoids.

PMID- 15141299
TI  - Computational approaches to structural and functional analysis of plastocyanin
      and other blue copper proteins.
AB  - Computational techniques are becoming increasingly important in structural and
      functional biology, in particular as tools to aid the interpretation of
      experimental results and the design of new systems. This review reports on recent
      studies employing a variety of computational approaches to unravel the
      microscopic details of the structure-function relationships in plastocyanin and
      other proteins belonging to the blue copper superfamily. Aspects covered include
      protein recognition, electron transfer and protein-solvent interaction properties
      of the blue copper protein family. The relevance of integrating diverse
      computational approaches to address the analysis of a complex protein system,
      such as a cupredoxin metalloprotein, is emphasized.

PMID- 15141302
TI  - Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of
      MAP kinases and NF-kappaB.
AB  - Taxol is a microtubule-stabilizing agent that has recently been shown effective
      in the treatment of experimental autoimmune encephalomyelitis, an animal model of
      multiple sclerosis. As astrocytes could modulate central nervous system (CNS)
      autoimmunity through inducible nitric oxide synthase (iNOS)-mediated production
      of immunoregulatory free radical nitric oxide (NO), we investigated the effect of
      taxol on NO synthesis in rat astrocytes. Taxol, either alone or in combination
      with interferon-gamma, induced NO generation in primary astrocytes and
      astrocytoma C6 cells in a dose- and time-dependent manner. Accordingly, the drug
      markedly up-regulated the expression of both iNOS mRNA and protein in astrocytes.
      The observed effect of taxol was mediated through induction of iNOS transcription
      factors NF-kappaB and IRF-1, and required the activation of p38 MAP kinase and
      JNK. Finally, NO release by taxol-stimulated astrocytes was blocked with the
      microtubule-depolymerizing agent colchicine, suggesting the involvement of a
      microtubule-stabilizing activity of taxol in the observed effect.

PMID- 15141303
TI  - Expression of the Stp1 LMW-PTP and inhibition of protein CK2 display a
      cooperative effect on immunophilin Fpr3 tyrosine phosphorylation and
      Saccharomyces cerevisiae growth.
AB  - Although the yeast genome does not encode bona fide protein tyrosine kinases,
      tyrosine-phosphorylated proteins are numerous, suggesting that besides dual
      specificity kinases, some Ser/Thr kinases are also committed to tyrosine
      phosphorylation in Saccharomyces cerevisiae. Here we show that blockage of the
      highly pleiotropic Ser/Thr kinase CK2 with a specific inhibitor synergizes with
      the overexpression of Stp1 low-molecular-weight protein tyrosine phosphatase
      (PTP) in inducing a severe growth-defective phenotype, consistent with a
      prominent role for CK2 in tyrosine phosphorylation in yeast. We also present in
      vivo evidence that immunophilin Fpr3, the only tyrosine-phosphorylated CK2
      substrate recognized so far, interacts with and is dephosphorylated by Spt1.
      These data disclose a functional correlation between CK2 and LMW-PTPs, and
      suggest that reversible phosphorylation of Fpr3 plays a role in the regulation of
      growth rate and budding in S. cerevisiae.

PMID- 15141304
TI  - An extensive microarray analysis of AAL-toxin-induced cell death in Arabidopsis
      thaliana brings new insights into the complexity of programmed cell death in
      plants.
AB  - A T-DNA knockout of the Arabidopsis homologue of the tomato disease resistance
      gene Asc was obtained. The asc gene renders plants sensitive to programmed cell
      death (PCD) triggered by the fungal AAL toxin. To obtain more insights into the
      nature of AAL-toxin-induced cell death and to identify genes of potential
      importance for PCD, we carried out transcription profiling of AAL-toxin-induced
      cell death in this knockout with an oligonucleotide array representing 21,500
      Arabidopsis genes. Genes responsive to reactive oxygen species (ROS) and ethylene
      were among the earliest to be upregulated, suggesting that an oxidative burst and
      production of ethylene played a role in the activation of the cell death. This
      notion was corroborated by induction of several genes encoding ROS-generating
      proteins, including a respiratory burst oxidase and germin oxalate oxidase.
      Cytochemical studies confirmed the oxidative burst and, in addition, showed
      synthesis of callose, a feature of the hypersensitive response. A diverse group
      of transcription factors was also induced. These events were followed by
      repression of most of the auxin-regulated genes known to be involved in growth
      and developmental responses. All photosynthesis-related genes were repressed.
      Blocking the synthesis of ethylene or NO significantly compromised cell death. In
      addition, we identified a heterogeneous group of early-induced genes, some of
      them never before associated with PCD. The group of early-induced genes included
      a number of proteases that were previously implicated in developmentally
      regulated types of PCD, suggesting a more principal role for these proteases in
      the PCD process. These findings provide new insights into the molecular
      mechanisms of plant PCD.

PMID- 15141301
TI  - Phylogenetic origin of LI-cadherin revealed by protein and gene structure
      analysis.
AB  - The intestine specific LI-cadherin differs in its overall structure from
      classical and desmosomal cadherins by the presence of seven instead of five
      cadherin repeats and a short cytoplasmic domain. Despite the low sequence
      similarity, a comparative protein structure analysis revealed that LI-cadherin
      may have originated from a five-repeat predecessor cadherin by a duplication of
      the first two aminoterminal repeats. To test this hypothesis, we cloned the
      murine LI-cadherin gene and compared its structure to that of other cadherins.
      The intron-exon organization, including the intron positions and phases, is
      perfectly conserved between repeats 3-7 of LI-cadherin and 1-5 of classical
      cadherins. Moreover, the genomic structure of the repeats 1-2 and 3-4 is
      identical for LI-cadherin and highly similar to that of the repeats 1-2 of
      classical cadherins. These findings strengthen our assumption that LI-cadherin
      originated from an ancestral cadherin with five domains by a partial gene
      duplication event.

PMID- 15141305
TI  - Profile identification of disease-associated humoral antigens using AMIDA, a
      novel proteomics-based technology.
AB  - We describe AMIDA (autoantibody-mediated identification of antigens), a novel
      target identification technology based on the immunoprecipitation of disease
      specific antigens by autologous serum antibodies followed by two-dimensional
      electrophoretic separation, and their identification via mass spectrometry.
      Twenty-seven potential carcinoma antigens were identified including proteins of
      hitherto unknown function. Validation of one of the identified antigens,
      cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual
      overexpression with increasing malignancy, and ectopic localization on the cell
      surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in
      the serum of cancer patients already at early disease stages. In situ
      hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its
      strong overexpression in head and neck carcinomas, thus making it a likely tumor
      antigen candidate. Eventually, AMIDA could foster significant improvements for
      the diagnosis and therapy of human diseases eliciting a humoral immune response,
      and allows for the rapid identification of new target molecules.

PMID- 15141306
TI  - Characterization of the yeast tricalbins: membrane-bound multi-C2-domain proteins
      that form complexes involved in membrane trafficking.
AB  - In a survey of yeast genomic sequences encoding calcium- and phospholipid-binding
      C2 domains, three homologous genes were identified that encode proteins that each
      have three C2 domains and an apparent transmembrane domain near the N terminus.
      The name tricalbins is suggested for these proteins, corresponding to the open
      reading frames YOR086c (TCB1), YNL087w (TCB2), and YML072c (TCB3). An antiserum
      was raised against the C-terminal portion of tricalbin 2 and used on Western
      blots to demonstrate that the corresponding protein is expressed in yeast and
      appears as a high-molecular-weight band at 130 kDa with smaller fragments at 39
      kDa and 46 kDa. A fusion protein consisting of full length tricalbin 2 fused to
      the green fluorescent protein was expressed in cells and found to traffic from
      the cell surface to intracellular vesicles near the vacuole. A two-hybrid
      interaction screen with the C-terminal portion of tricalbin 2 indicated that
      tricalbin 2 binds the C-terminal portions of tricalbins 1 and 3 suggesting that
      the tricalbins may form heterodimers in vivo. Tricalbin 2 also interacted with
      the activation domain of the pleiotropic drug resistance transcription factor
      Pdr1p. Combinatorial disruptions of the tricalbin genes revealed that tcb2 single
      mutants or tcb1, tcb3 double mutants have an altered vacuole morphology and are
      hypersensitive to cycloheximide. A screen for single-copy suppressors of the
      cycloheximide sensitivity of tricalbin mutants yielded RSP5, which encodes a C2
      domain-containing, ubiquitin-conjugating ligase essential for receptor-mediated
      and fluid phase endocytosis. The results suggest that the tricalbins function as
      multimers in membrane-trafficking events and may provide insights into the roles
      of multi-C2-domain proteins, such as the synaptotagmins, in other organisms.

PMID- 15141307
TI  - Apoptotic cell death in the lactating mammary gland is enhanced by a folding
      variant of alpha-lactalbumin.
AB  - Apoptosis is essential to eliminate secretory epithelial cells during the
      involution of the mammary gland. The environmental regulation of this process is
      however, poorly understood. This study tested the effect of HAMLET (human alpha
      lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets
      containing HAMLET were implanted into the fourth inguinal mammary gland of
      lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in
      morphological changes typical for apoptosis and in a stimulation of caspase-3
      activity in alveolar epithelial cells near the HAMLET pellets but not more
      distant to the pellet or in contralateral glands. The effect was specific for
      HAMLET and no effects were observed when mammary glands were exposed to native a
      lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a
      mouse mammary epithelial cell line. The results suggest that HAMLET can mediate
      apoptotic cell death in mammary gland tissue.

PMID- 15141308
TI  - Periplasmic lysozyme inhibitor contributes to lysozyme resistance in Escherichia
      coli.
AB  - The product of the Escherichia coli ORFan gene ykfE was recently shown to be a
      strong inhibitor of C-type lysozyme in vitro. The gene was correspondingly
      renamed ivy (inhibitor of vertebrate lysozyme), but its biological function in E.
      coli remains unknown. In this work, we investigated the role of Ivy in the
      resistance of E. coli to the bactericidal effect of lysozyme in the presence of
      outer-membrane-permeabilizing treatments. Both in the presence of lactoferrin
      (3.0 mg/ml) and under high hydrostatic pressure (250 MPa), the lysozyme
      resistance of E. coli MG1655 was decreased by knock-out of Ivy, and increased by
      overexpression of Ivy. However, knock-out of Ivy did not increase the lysozyme
      sensitivity of an E. coli MG1655 mutant previously described to be resistant to
      lysozyme under high pressure. These results indicate that Ivy is one of several
      factors that affect lysozyme resistance in E. coli, and suggest a possible
      function for Ivy as a host interaction factor in commensal and pathogenic E.
      coli.

PMID- 15141309
TI  - Olfactory ensheathing cells promote neurite sprouting of injured axons in vitro
      by direct cellular contact and secretion of soluble factors.
AB  - Olfactory ensheathing cells (OECs) represent an exciting possibility for
      promoting axonal regeneration within the injured spinal cord. A number of studies
      have indicated the ability of these cells to promote significant reactive
      sprouting of injured axons within the injured spinal cord, and in some cases
      restoration of functional abilities. However, the cellular and/or molecular
      mechanisms OECs use to achieve this are unclear. To investigate such mechanisms,
      we report for the first time the ability of OECs to promote post-injury neurite
      sprouting in an in vitro model of axonal injury. Using this model, we were able
      to differentiate between the direct and indirect mechanisms underlying the
      ability of OECs to promote neuronal recovery from injury. We noted that OECs
      appeared to act as a physical substrate for the growth of post-injury neurite
      sprouts. We also found that while post-injury sprouting was promoted most when
      OECs were allowed to directly contact injured neurons, physical separation using
      tissue culture inserts (1 mm pore size, permeable to diffusible factors but not
      cells) did not completely block the promoting properties of OECs, suggesting that
      they also secrete soluble factors which aid post-injury neurite sprouting.
      Furthermore, this in vitro model allowed direct observation of the cellular
      interactions between OECs and sprouting neurites using live-cell-imaging
      techniques. In summary, we found that OECs separately promote neurite sprouting
      by providing a physical substrate for growth and through the expression of
      soluble factors. Our findings provide new insight into the ability of OECs to
      promote axonal regeneration, and also indicate potential targets for manipulation
      of these cells to enhance their restorative ability.

PMID- 15141310
TI  - Sequential proteome alterations during genesis and progression of colon cancer.
AB  - Changes in the proteome of colon mucosal cells accompany the transition from
      normal mucosa via adenoma and invasive cancer to metastatic disease. Samples from
      15 patients with sporadic sigmoid cancers were analyzed. Proteins were separated
      by two-dimensional gel electrophoresis. Relative differences in expression levels
      between normal tissue, adenoma, carcinoma and metastasis were evaluated in both
      intra- and inter-patient comparisons. Up- and down-regulated proteins (> twofold)
      during development to cancer or metastasis were excised and submitted to peptide
      mass fingerprinting and MS/MS sequence analysis, facilitated by the use of a
      compact disc workstation. In total, 112 protein spots were found to be
      differentially regulated, of which 72 were determined as to protein identity, 46
      being up-regulated toward the progression of cancer, and 26 down-regulated.
      Several of the identifications correlate with proteins of the cell cycle,
      cytoskeleton or metabolic pathways. The pattern changes now identified have the
      potential for design of marker panels for assistance in diagnostics and
      therapeutic strategies in colorectal cancer.

PMID- 15141311
TI  - Prevalence of dog bites in children: a telephone survey.

PMID- 15141313
TI  - Pulmonary papillary adenoma-like tumour arising in ovarian teratoma.

PMID- 15141312
TI  - Withholding initial vancomycin in febrile neutropenia despite implanted
      catheters.

PMID- 15141314
TI  - Clear-cell adenoma of the fallopian tube, a rare tumor of the tubal mucosa.

PMID- 15141315
TI  - Bioavailability of 239+240Pu and 137Cs in aerosols and deposited dusts: a
      comparative study by fractional extraction.
AB  - The bioavailability of (137)Cs and (239+240)Pu in soil, dust and aerosols has
      been determined by applying a fractional extraction procedure. In aerosols, 47
      57% of (137)Cs was found to be easily exchangeable. This differs significantly
      from soil and deposited dust samples collected on a nearby street as well as on
      grassland where (137)Cs was quantitatively found in the acid-soluble fraction and
      the residue. A similar difference was observed for (239+240)Pu: 47% of
      (239+240)Pu in aerosols was associated with the organic fraction, while in soil
      and deposited dust from grassland 63-75% of (239+240)Pu was found in the acid
      soluble fraction. In deposited street dust, 53% of (239+240)Pu was associated
      with the oxide fraction.

PMID- 15141316
TI  - Immunophenotype and possible origin of nevi with phenotypical heterogeneity.
AB  - Biphenotypical nevi or nevi with phenotypical heterogeneity consist of
      phenotypically different cell populations in a pattern other than that observed
      in classical combined nevi or in various maturation stages of banal nevocellular
      nevi. Besides several well-known entities such as deep penetrating nevi and
      plexiform spindle cell nevi, this category of pigment cell lesions also harbors
      fewer delineated lesions such as nevi with atypical dermal nodules (N-ADN) and
      nevi with a focal atypical epithelioid cell component (N-FAECC). Their worrisome
      histology may result in a wrong diagnosis of malignancy. In order to discriminate
      them from malignant melanoma and to shed light on their histogenesis, we analyzed
      the immunophenotypical profile of 33 N-FAECC, 6 N-ADN, and 10 giant congenital
      nevi removed shortly after birth, using antibodies directed to S100 protein,
      gp100, tyrosinase, NKI-C3, Melan-A and Mib-1. In N-FAECC and N-ADN, the large
      polygonal cells expressed gp100, S100 protein and Melan-A, and reacted with
      monoclonal antibody NKI-C3. In addition, there was intense tyrosinase expression
      but no Mib-1 immunoreactivity. Unexpectedly, we observed similar single or
      clustered, large epithelioid cells in three out of ten giant congenital nevi;
      these cells showed a similar phenotype to those observed in N-ADN and N-FAECC.
      Our histological and immunohistochemical data suggest that N-FAECC and N-ADN may
      reflect different stages of the same disorder. Moreover, their resemblance to the
      large polygonal cells in congenital nevi may suggest that the histogenesis of N
      ADN and N-FAECC may be related to the persistence and expansion of large
      epithelioid cells in congenital nevi shortly after birth.

PMID- 15141318
TI  - Ipsilateral dislocation of knee, foot and ankle.
AB  - We present a case of ipsilateral dislocation of the knee, ankle and midfoot. No
      previous report of this combination of injuries was found in a review of the
      literature. In spite of the type of injury, no neurovascular compromise or
      complications turned up. Closed reduction of the dislocations was possible and
      performed under general anaesthesia. At the last examination, 4 years after
      injury, the alignment of the joints was preserved, and the range of motion of the
      three joints resembled that of the opposite side. Without fractures, the closed
      reduction and temporary immobilisation of all the affected joints produced a
      remarkably good result.

PMID- 15141317
TI  - A study of cytokeratin profiles in localized cutaneous amyloids.
AB  - The major component of localized cutaneous amyloids may be derived from
      cytokeratin (CK). However, the CK profiles of primary cutaneous amyloidosis (PCA)
      and secondary cutaneous amyloidosis (SCA) remain obscure. Paraffin-embedded
      sections of skin tissue from 64 patients with PCA, 111 with SCA and 3 with
      systemic amyloidosis were analyzed immunohistochemically using 12 different
      polyclonal or monoclonal anti-CK antibodies (34betaE12, MNF116, LP34, AE1/AE3,
      anti-CK1, CK5, CK6, CK7, CK10, CK14, CK16 and CK17). In addition, frozen skin
      tissues from 12 patients with PCA were analyzed for comparison with the paraffin
      embedded tissue. In all 64 PCA paraffin sections, the amyloid deposits were
      immunopositive for anti-CK5 antibody and 34betaE12. In all 12 frozen sections of
      PCA, the amyloid deposits were immunopositive for anti-CK5 antibody, 34betaE12,
      MNF116 and LP34, and seven (58.3%), three (25%) and one (8.3%) were
      immunopositive for anti-CK1, CK14, and CK10 antibodies, respectively. In all SCA
      sections, the amyloid deposits were immunopositive for CK5 and 34betaE12. In
      addition, MNF116 immunolabeled amyloids of all sections from patients with basal
      cell carcinoma and trichoepithelioma, and MNF116 and LP34 immunolabeled amyloids
      of sections from patients with porokeratosis. Our results indicate that CK5 is
      the major CK present in the amyloid deposits of PCA and SCA, and "amyloid-K" is
      mainly derived from basal keratinocytes.

PMID- 15141319
TI  - Anorectal malformation with congenital absence of vagina: a case report and
      review of the literature.
AB  - Congenital anorectal malformations are relatively common, and associated
      genitourinary malformations have been reported in up to 40% of patients.
      Uterovaginal malformations are also not rare in children. They are known to occur
      with increased frequency in children with anorectal malformations, but the
      diagnosis may still be difficult. We report herein one such case of anorectal
      malformation associated with congenital total absence of the vagina in which the
      uterovaginal malformation was not diagnosed until the operative repair of the
      anorectal malformation. The operative procedure was thereafter directed, along
      with the anorectoplasty, towards restoring a functional uterovaginal tract.
      Review of the literature revealed that such a diagnosis is unsuspected or delayed
      in more than half of affected patients. Furthermore, these patients present with
      many diagnostic and therapeutic problems. Our report highlights the need to be
      aware of this condition to allow for an earlier diagnosis and appropriate
      operative treatment.

PMID- 15141321
TI  - The effect of intestinal plication on intestinal transit time in rats.
AB  - Short bowel syndrome (SBS) can occur after extensive intestinal resections. In
      SBS, the aim of surgical techniques is to prolong intestinal transit time (ITT)
      and to increase the absorptive surface. This experimental study was conducted to
      research the effect of extramucosal intestinal plication on ITT in rats. Thirty
      Sprague-Dawley rats were divided into three groups. In the control group, barium
      solution was administrated by gavage. Forty-five minutes later, the rats were
      sacrificed, and the total length of their small bowels (SBs) and the distance of
      the barium in the SBs were measured. The ratio of the distance of the barium to
      the length of the SB was calculated, and the ITT was found for normal rats.
      Intestinal plication (made with three seromuscular sutures at the same level: one
      on the antimesenteric side, and two on the lateral sides of the bowel) and
      laparotomy and bowel manipulation were carried out in the study and sham groups,
      respectively, and ITT was measured by the same method after 1 week. A one-way
      ANOVA test was used to compare the groups in terms of body weight, total length
      of the SB, distance of the barium in the SB, and the ratio of this distance to
      the length of the SB. The rats were statistically homogeneous in terms of body
      weight and total length of the SB ( p>0.05). The distances of the barium in the
      small bowel in the control, sham, and study groups were 73.4+/-8.5 cm, 77.5+/-6.8
      cm, and 56.3+/-3.6 cm, respectively. The distances of barium in the SB in the
      study group were statistically shorter than in the other groups ( p<0.05). The
      ratios of the distance of the barium to the length of the SB in the control,
      sham, and study groups were 65.8+/-7.3, 66.4+/-4.5, and 49.9+/-3.8, respectively.
      In the study group, this ratio was also statistically lower than in the other
      groups ( p<0.05). Extramucosal intestinal plication retarded ITT significantly in
      the study group compared with the other groups. This technique does not entail
      any risk of morbidity and mortality; therefore, it can be used in the treatment
      of SBS.

PMID- 15141320
TI  - Clinical manifestations of appendiceal pinworms in children: an institutional
      experience and a review of the literature.
AB  - The association of Enterobius vermicularis infestation with acute appendicitis
      varies from 0.2-41.8% worldwide. Our purpose was to determine the significance of
      Enterobius-associated appendicitis by retrospective review of appendectomies
      performed during a 5-year period at a major children's hospital. The Surgical
      Pathology database at Children's Hospital, Columbus, Ohio, was reviewed for
      appendiceal specimens found to have Enterobius infestation. Corresponding patient
      charts were evaluated for age, gender, presenting symptoms, laboratory data,
      operative findings, and clinical course. Of the 1,549 appendectomies performed
      from January 1998 through January 2003, 21 specimens (1.4%) were found to contain
      Enterobius vermicularis. Fifteen of the appendectomies were performed for
      symptoms of acute appendicitis; the remaining six were incidental appendectomies
      in conjunction with other operations. The mean age was 8.9 years. Ten patients
      were male; 11 were female. Of the 15 symptomatic children, nine presented with
      fever >99.0 degrees F, and 11 had a WBC count >10,000. Intra-operative appearance
      of the appendix ranged from normal to perforation. Pathologic evaluation showed
      neutrophil or eosinophil infiltration in 15 of the 21 specimens. Enterobius
      infestation is an uncommon cause of acute appendicitis in children in the United
      States. It may be associated with acute appendicitis, "chronic appendicitis,"
      ruptured appendicitis, or with no significant clinical symptoms.

PMID- 15141323
TI  - T-cell clonal disorder in acquired primary pure red cell aplasia.

PMID- 15141322
TI  - Somatic embryogenesis and plant regeneration from immature zygotic embryos of
      Hinoki cypress (Chamaecyparis obtusa Sieb. et Zucc.).
AB  - We established a plant regeneration system for Hinoki cypress (Chamaecyparis
      obtusa) via somatic embryogenesis. Embryogenic tissues were successfully induced
      on three kinds of Smith media from megagametophyte explants containing pre
      cotyledonary embryos of C. obtusa plus-trees. Factors affecting somatic embryo
      maturation were examined. The concentration of polyethylene glycol 4000 in the
      medium was a critical factor for embryo maturation and its effective
      concentration was 150 g/l. The addition of 30 g/l maltose to the medium had a
      positive effect on embryo maturation, but sucrose was ineffective. The mature
      somatic embryos germinated at a germination frequency of approximately 60%, and
      the presence of activated charcoal was effective in stimulating plantlet growth.
      The plantlets acclimatized successfully in a greenhouse. To our knowledge, this
      is first report describing details of a plant regeneration method for C. obtusa
      via somatic embryogenesis.

PMID- 15141324
TI  - Frequency of the C282Y and H63D mutations of the hemochromatosis gene (HFE) in
      2501 ethnic Danes.
AB  - The aim of the study was to assess the frequency of the C282Y and H63D mutations
      of the hemochromatosis gene (HFE) in ethnic Danes. The series comprised 2501
      subjects (1284 men) of Danish heritage who were drawn at random from the Census
      Registry in age cohorts of 30, 40, 50, and 60 years. The frequency of the C282Y
      and H63D mutations was assessed on blood samples by genotyping using a polymerase
      chain reaction (PCR) technique. The HFE genotype distribution was in Hardy
      Weinberg equilibrium (p=0.85). C282Y mutation: 9 subjects (0.36%) were homozygous
      and 265 subjects (10.6%) were heterozygous. H63D mutation: 40 subjects (1.6%)
      were homozygous and 584 subjects (23.4%) were heterozygous. C282Y/H63D compound
      heterozygosity was found in 36 subjects (1.4%). The C282Y allele frequency was
      5.7% [95% confidence interval (CI) 5.0-6.3%] and the H63D allele frequency was
      13.3% (95% CI 12.3-14.2%). In conclusion, the C282Y frequency is relatively high
      in the Danes, being close to the frequency in other Scandinavian countries, i.e.,
      Iceland 5.1%, the Faroe Islands 6.6%, and Sweden 5.7%, but significantly lower
      than in Norway 6.6% (p=0.02). Also, the H63D frequency in Danes is close to and
      not significantly different from the frequency in Iceland 10.9%, Norway 11.2%,
      and Sweden 12.4%, but significantly lower than in the Faroe Islands 15.4%
      (p=0.046).

PMID- 15141329
TI  - Endovascular therapy for acute thrombotic occlusion of the intracranial artery.
AB  - The goal of this study was to evaluate the efficacy of endovascular therapy for
      acute thrombotic occlusion. Six patients with acute thrombotic occlusion in the
      middle cerebral or basilar arteries underwent treatment with intra-arterial
      thrombolysis, followed by assessment of residual stenosis. If residual stenosis
      was greater than 70%, percutaneous transluminal angioplasty (PTA) was performed
      in the same session; otherwise, patients were anticoagulated, and PTA was
      performed several days later. Successful recanalization was achieved in five of
      six patients. One patient died of massive infarction, because of the failure of
      recanalization of the M1 segment. At discharge, modified Rankin scale
      distribution of the patients was: grade 0, one patient; grade 1, one patient;
      grade 2, two patients; grade 3, one patient; grade 6, one patient. Retreatment
      was required via PTA or stenting in two patients in which type C stenosis was
      present. In conclusion, endovascular therapy for acute thrombotic occlusion of an
      intracranial artery appears to be effective compared to conservative therapy.
      However, further refinement of the technique is required to prevent various
      complications, including vessel perforation, dissection, perforating artery
      occlusion and restenosis.

PMID- 15141328
TI  - Posterior cranial fossa single-hole arteriovenous fistulae in children: 14
      consecutive cases.
AB  - We report 14 consecutive children with 23 posterior cranial fossa arteriovenous
      fistula (AVF); six had multifocal lesions, involving the supratentorial brain in
      three and the spinal cord in one. There were two boys and four girls with a
      family history compatible with hereditary haemorrhagic telangiectasia. The
      diagnosis was made in infancy in eight cases and in a further six before the age
      of 12 years; mean age at diagnosis was 3.5 years. The male-to-female ratio was
      1.8:1. Presenting features were macrocrania in four cases, haemorrhage or
      headache in three and nonhaemorrhagic neurological deficits or and cardiac
      overload in two. Dominant supply to the symptomatic fistula arose from the
      posterior inferior cerebellar artery in five cases, anterior inferior cerebellar
      artery in two and the upper basilar artery system in seven. All children were
      primarily treated by transarterial embolisation. We treated thirteen children
      (93%) by transarterial embolisation alone; one older child with a history of
      haemorrhage also underwent radiosurgery. We obtained 100% exclusion of the
      fistula(e) in six children, 95-80% in five, 80-50% in one and <50% in one. Of the
      incompletely treated cases, three had conservative management, and two with 80%
      and one with 60% reduction of their lesion are scheduled for elective treatment;
      two partially treated case died. There was no morbidity due to the endovascular
      procedures. Follow-up since referral is 6 months-10 years (mean 4.5 years). Ten
      children are neurologically normal, two have persistent (pre-existing)
      neurological deficits and two are dead.

PMID- 15141325
TI  - Proliferation-dependent changes in amino acid transport and glucose metabolism in
      glioma cell lines.
AB  - Amino acid imaging is increasingly being used for assessment of brain tumor
      malignancy, extent of disease, and prognosis. This study explores the
      relationship between proliferative activity, amino acid transport, and glucose
      metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of
      growth in culture. Growth phase was characterized by direct cell counting,
      proliferation index determined by flow cytometry, and [(3)H]thymidine (TdR)
      accumulation, and was compared with the uptake of two non-metabolized amino acids
      ([(14)C]aminocyclopentane carboxylic acid (ACPC) and [(14)C]aminoisobutyric acid
      (AIB)), and [(18)F]fluorodeoxyglucose (FDG). Highly significant relationships
      between cell number (density), proliferation index, and TdR accumulation rate
      were observed in all cell lines ( r>0.99). Influx ( K(1)) of both ACPC and AIB
      was directly related to cell density, and inversely related to the proliferation
      index and TdR accumulation in all cell lines. The volume of distribution ( V(d))
      for ACPC and AIB was lowest during rapid growth and highest during the near
      plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells
      was unaffected by proliferation rate, growth phase, and cell density, whereas FDG
      accumulation was correlated with TdR accumulation, growth phase, and cell density
      in U87 cells. This study demonstrates that proliferation rate and glucose
      metabolism are not necessarily co-related in all glioma cell lines. The values of
      K(1) and V(d) for ACPC and AIB under different growth conditions suggest that
      these tumor cell lines can up-regulate amino acid transporters in their cell
      membranes when their growth conditions become adverse and less than optimal.

PMID- 15141330
TI  - Pregraduate teaching clinical pharmacology in Germany.

PMID- 15141331
TI  - The pharmacokinetics of eflornithine (alpha-difluoromethylornithine) in patients
      with late-stage T.b. gambiense sleeping sickness.
AB  - OBJECTIVE: To investigate the plasma, cerebrospinal fluid (CSF) levels and
      pharmacokinetics of eflornithine (DFMO) in patients with late-stage T.b.
      gambiense sleeping sickness who were treated with an oral DFMO at 100 mg/kg or
      125 mg/kg body weight every 6 h for 14 days. METHODS: Plasma and CSF
      concentrations of DFMO were measured during day 10 and day 15 in patients
      following oral DFMO at 100 mg/kg (group I: n=12) and 125 mg/kg (group II: n=13)
      body weight every 6 h for 14 days. Clinical and parasitological assessments were
      performed at 24 h after the last dose of DFMO and at 12 months. RESULTS: Patients
      in each group had a good initial response, but relapse was observed in six
      patients (three patients for each group) during 12 months follow-up. Plasma DFMO
      concentrations did not increase proportionally to doses when the dose increased
      from 100 mg/kg to 125 mg/kg body weight given every 6 h (60-70% of the expected
      increase). In most cases, concentration-time profiles of DFMO in each group were
      best fit using a two-compartment open model with first-order input, with
      absorption lag-time and first-order elimination. Average trough (C(ss-min)) and
      average (C(ss-ave)) plasma DFMO concentrations during steady state varied between
      189-448 nmol/ml and 234-528 nmol/ml, following 100 mg/kg and 125 mg/kg dose
      group, respectively. C(max), t(max) and AUC(0- infinity ) values following the
      last dose were 296-691 nmol/l, 2-3 h, and 2911-6286 nmol h/ml, respectively.
      V(z)/F, CL/F and t(1/2z) values were 0.47-2.66 l/kg, 0.064-0.156 l/h/kg, and 3.0
      16.3 h, respectively. CSF concentrations at steady state varied between 22.3
      nmol/ml and 64.7 nmol/ml. Patients who had treatment failure tended to have lower
      plasma and CSF DFMO concentrations than those who had successful treatment.
      CONCLUSION: Oral DFMO at the dose of 125 mg/kg body weight given every 6 h for 14
      days may not produce adequate therapeutic plasma and CSF levels for patients with
      late-stage T.b. gambiense sleeping sickness.

PMID- 15141332
TI  - The role of NF-kappaB in 6-hydroxydopamine- and TNFalpha-induced apoptosis of
      PC12 cells.
AB  - 6-Hydroxydopamine (6-OHDA) is widely used to study the death of catecholaminergic
      cells related to Parkinson's disease. Oxidative stress and gene transcription are
      known to mediate the pro-apoptotic effect of 6-OHDA. As redox mechanisms are
      involved in activation of the transcription factor NF-kappaB, we studied the role
      of NF-kappaB in 6-OHDA-induced death of PC12 cells. We stably transfected PC12
      cells with a doxycycline-regulated expression vector for the NF-kappaB super
      repressor (IkappaBalpha mutated at serine-32 and serine-36, IkappaBalpha-SR). NF
      kappaB transcriptional activity was evaluated by transient transfection of an NF
      kappaB-driven luciferase reporter gene. Expression of IkappaBalpha-SR inhibited
      NF-kappaB stimulated by tumor necrosis factor alpha (TNFalpha) and 6-OHDA.
      Apoptosis was quantified by counting cells with condensed nuclei. IkappaBalpha-SR
      inhibited apoptosis induced by 6-OHDA but enhanced apoptosis that was triggered
      by TNFalpha. The converse effects of NF-kappaB could be due to different target
      genes that are induced in the context of TNFalpha and 6-OHDA stimulation. Indeed,
      TNFalpha stimulated mRNA accumulation of the anti-apoptotic superoxide dismutase
      2 through NF-kappaB whereas 6-OHDA induced mRNA accumulation of the pro-apoptotic
      c-myc. These data demonstrate that NF-kappaB regulates survival of the neuron
      like PC12 cells in a stimulus-specific manner. In the context of 6-OHDA
      stimulation, NF-kappaB mediates pro-apoptotic effects, suggesting that NF-kappaB
      signaling could be a target for drug development in Parkinson-related
      neurodegeneration.

PMID- 15141333
TI  - Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients:
      limited value for diagnosis of tuberculous meningitis.
AB  - Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is
      considered a specific test for the diagnosis of tuberculous meningitis. In order
      to study the variability of this marker in patients with different neurological
      disorders associated with HIV infection, and its utility for the diagnosis of
      tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from
      HIV-infected patients with neurological symptoms were reviewed. HIV infection,
      HIV-associated neurological disorders, and progressive multifocal
      leukoencephalopathy were not associated with elevated ADA in CSF. Among patients
      with meningitis, receiver operating characteristic curve analysis gave an optimal
      ADA cut-off point of 8.5 IU/l for the diagnosis of tuberculous meningitis, with
      57% sensitivity, 87% specificity, and an area under the curve of 0.747 (similar
      to that for CSF glucose concentration). False-positive results were found in
      patients with neurological CMV disease and cryptococcal, lymphomatous, and
      probable candidal meningitis. The results of this study indicate that ADA
      determination in CSF has limited utility for the diagnosis of tuberculous
      meningitis in HIV-infected patients.

PMID- 15141334
TI  - Non- epidermidis coagulase-negative staphylococcal bacteremia: clinical
      predictors of true bacteremia.
AB  - In order to explore the clinical significance and risk factors for true
      bacteremia caused by coagulase-negative staphylococci (CNS) other than
      Staphylococcus epidermidis, a retrospective cohort study of 160 patients with at
      least one blood culture positive for non- epidermidis CNS was performed. True
      bacteremia was diagnosed in 32 (20%) of the patients. On multivariate analysis
      the following factors were associated with true bacteremia: (i) more than one
      positive blood culture, (ii) presence of a central venous catheter, and (iii)
      methicillin resistance. The results of this study indicate that non- epidermidis
      CNS can cause significant bloodstream infections.

PMID- 15141335
TI  - Meropenem therapy failure in Listeria monocytogenes infection.
AB  - Listeria monocytogenes is highly susceptible to meropenem in vitro, but data on
      the efficacy of meropenem in clinical cases of listeriosis are scarce. Described
      here is the case of a child with aplastic anemia who acquired nosocomial
      listeriosis and failed to respond to initial meropenem therapy. Resolution of
      fever was not noted after 5 days of therapy with meropenem and, more importantly,
      clinical worsening was observed during this period. The patient began to improve
      after ampicillin was introduced to the therapeutic regimen. In total, meropenem
      was administered for 15 days and ampicillin for 10 days.

PMID- 15141336
TI  - In vitro activity of amphotericin B, fluconazole and voriconazole against 162
      Cryptococcus neoformans isolates from Africa and Cambodia.
AB  - In order to determine the potential role that various antifungal agents might
      have in the management of cryptococcosis in tropical areas, the in vitro
      susceptibility of Cryptococcus neoformans isolates from Africa ( n=52) and
      Cambodia ( n=110) to three antifungal agents (amphotericin B, fluconazole and
      voriconazole) were compared using the E-test method. The results of this study
      (i) confirm the value of the E-test for testing the in vitro susceptibility of C.
      neoformans towards voriconazole; (ii) provide the first evidence demonstrating
      good activity of amphotericin B, fluconazole and voriconazole against Cambodian
      isolates; and (iii) show there are differences in susceptibility between African
      and Asian C. neoformans isolates, with Cambodian isolates appearing less
      susceptible to the agents tested but with amphotericin B maintaining good
      activity.

PMID- 15141337
TI  - Clinical significance of lower respiratory tract Aspergillus culture in elderly
      hospitalized patients.
AB  - In order to evaluate the clinical significance of Aspergillus-positive culture
      results from the lower respiratory tract specimens of elderly hospitalized
      patients, and to identify the clinical variables that differentiate between
      colonization and infection with Aspergillus spp. in this patient population, a
      retrospective study was conducted. The records of 66 elderly patients whose lower
      respiratory tract specimens yielded Aspergillus spp. between January 1995 and
      July 2000 were examined. The majority of the patients ( n=61) were determined to
      be colonized with Aspergillus spp., and serious lung infection due to Aspergillus
      spp. was rare. Clinical, radiological, and microbiological data did not help
      differentiate between infection and colonization.

PMID- 15141338
TI  - Chlamydophila abortus infection in a pregnant woman associated with indirect
      contact with infected goats.
AB  - Reported here is the case of a pregnant woman who developed a severe
      Chlamydophila abortus infection after indirect contact with infected goats
      resulting in preterm stillbirth. The woman fully recovered after treatment with
      doxycycline. In the goat herd with which her husband worked Chlamydophila abortus
      was actively circulating, as shown by positive serology. When pregnant women
      present with rapidly worsening influenza-like illness, special attention should
      be given to possible contact (direct or indirect) with animals when recording the
      anamnesis. Pregnant women, especially those who live in rural areas, should
      generally be made aware of the risks of zoonotic diseases and how to avoid them.

PMID- 15141339
TI  - Lymphocyte surge as a marker for immunorestitution disease due to Pneumocystis
      jiroveci pneumonia in HIV-negative immunosuppressed hosts.

PMID- 15141340
TI  - Successful treatment of Wernicke encephalopathy in terminally ill cancer
      patients: report of 3 cases and review of the literature.
AB  - Although Wernicke encephalopathy has been reported in the oncological literature,
      only one terminally ill cancer patient with Wernicke encephalopathy has been
      reported. Wernicke encephalopathy, a potentially reversible condition, may be
      unrecognized in terminally ill cancer patients. In this communication, we report
      three terminally ill cancer patients who developed Wernicke encephalopathy. Early
      recognition and subsequent treatment resulted in successful palliation of
      delirium. Two of the three patients did not show the classical triad of Wernicke
      encephalopathy. Common clinical symptoms were delirium and poor nutritional
      status. Intravenous thiamine administration dramatically improved the symptoms of
      delirium in all three patients. In terminally ill cancer patients, clinicians
      must remain aware of the possibility of Wernicke encephalopathy when patients
      with a poor nutritional status present with unexplained delirium. Early
      intervention may correct the symptoms and prevent irreversible brain damage and
      the quality of life for the patient may improve.

PMID- 15141341
TI  - Elevated levels of vascular endothelial growth factor in serum of patients with
      D+ HUS.
AB  - The pathogenesis of hemolytic uremic syndrome (D+ HUS) is characterized by
      endothelial damage of glomeruli and tubules within the kidney. In several other
      diseases in which glomerular endothelial damage occurs, elevated serum levels of
      vascular endothelial growth factor (VEGF) have been reported. VEGF is involved in
      angiogenesis, permeabilization of blood vessel endothelium, and wound repair. In
      this study we evaluated VEGF levels in the serum of 40 D+ HUS patients in the
      acute phase and during the course of the disease. VEGF levels were measured using
      a double-sandwich ELISA. Indirect immunohistochemistry was performed for the
      detection of VEGF in renal biopsy material of 3 HUS patients. Significantly
      elevated VEGF levels were found in HUS patients compared with controls in both
      serum ( P<0.001) and plasma ( P<0.05). A significant relationship was found
      between VEGF levels and severity of the disease according to the classification
      of Gianantonio ( P<0.05). Levels of VEGF in blood increased during the 2nd and
      3rd week after HUS was diagnosed. Immunohistochemistry of renal biopsy material
      showed increased levels of the receptors for VEGF in the glomeruli. During the
      course of HUS, plasma VEGF levels increase and the increase is dependent on the
      severity of the disease. This is probably associated with the repair process.

PMID- 15141342
TI  - New Vitamin D analogues for osteodystrophy in chronic kidney disease.
AB  - Vitamin D therapy for patients with chronic kidney disease has until recently
      comprised alfacalcidol or calcitriol, both of which effectively attenuate
      secondary hyperparathyroidism and the target organ consequences thereof.
      Unfortunately, both these agents also have significant calcaemic and
      phosphataemic actions leading to frequent episodes of hypercalcaemia,
      hyperphosphataemia and an increase in the CaxP product. It is likely that these
      in turn have adverse effects on cardiovascular and survival outcomes by promoting
      soft tissue and vascular calcification. These drawbacks have fuelled a search for
      vitamin D compounds with a wider therapeutic window. Experimentally, some of
      these have exhibited remarkable dissociation between their ability to suppress
      parathyroid hormone (PTH) and concomitant calcaemic actions. In the case of 22
      oxacalcitriol, the calcaemic potency relative to parathyroid suppression is 100th
      of that of calcitriol. 22-oxacalcitriol, with paricalcitol and doxercalciferol,
      are now widely used. Clinical studies of these agents, while confirming efficacy
      that is at least as good as alfacalcidol/calcitriol, have not consistently shown
      benefit in head to head comparison. Experience with these agents in the
      paediatric arena is very limited. One placebo-controlled study has now been
      completed in children-paricalcitol appeared effective and well tolerated.
      Calcimimetics, which simultaneously lower PTH, calcium and the CaxP product are
      about to enter the clinical arena-early studies in adults look promising,
      although they will need careful evaluation in children. These two therapies are
      likely to be additive and will probably complement one another effectively.

PMID- 15141344
TI  - Mycophenolate mofetil as an alternative to cyclosporine in post renal transplant
      thrombocytopenia.

PMID- 15141343
TI  - HIV-associated nephropathy and end-stage renal disease in children in the United
      States.
AB  - Single-center studies have reported that HIV-associated nephropathy (HIVAN) can
      occur in children and may have a clinical course and prognosis similar to that of
      adults. However, the prevalence and survival has not been reported for a national
      sample of children with HIVAN and end-stage renal disease (ESRD) on dialysis in
      the United States. We utilized the United States Renal Data System (USRDS)
      database to determine the prevalence, demographic information, and survival of
      children with HIVAN and ESRD in the United States. The Kaplan-Meier method was
      used to estimate survival of children with HIVAN and the log-rank test was used
      to compare their survival with children with focal segmental glomerulosclerosis
      (FSGS) and adults with HIVAN. Cox regression analysis was used to model adjusted
      hazard ratios (AHR) with HIVAN as a cause of ESRD and its impact on mortality
      during the study period, adjusted for potential confounders. Of the 7,732
      patients identified with HIVAN, only 60 were younger than 21 years and were
      classified as children; 50% were males and the majority (88.3%) was black. The
      cumulative percentage survival of children with HIVAN at 12, 24, and 36 months
      was better than adults with HIVAN (76%, 62%, and 54% vs. 60%, 43%, and 34%).
      Survival of children with HIVAN who started dialysis after 1996 was significantly
      better than those who started dialysis in or before 1996 (log rank P value
      <0.043). However, the major factor associated with better survival on Cox
      proportional hazard analysis was female gender (male vs. female AHR 2.85, 95%
      confidence interval 1.04-6.73). We conclude that only a small number of children
      with HIVAN and ESRD have received dialysis in the United States. The prognosis of
      these children is better than that of adults with HIVAN and among children with
      HIVAN females have better survival than males.

PMID- 15141345
TI  - Vitamin D receptor gene polymorphism in hypercalciuric children.
AB  - Idiopathic hypercalciuria is a complex disease resulting from an interaction
      between environmental and genetic factors. Recently, the relationship between
      vitamin D receptor ( VDR) alleles and calcium homeostasis has been investigated.
      This study was conducted to explore the association of VDR gene polymorphism with
      the risk of absorptive hypercalciuria (AH). We investigated the VDR gene
      polymorphisms, ApaI, BsmI, and TaqI, in relation to intact parathormone (PTH),
      osteocalcin, and 25-hydroxyvitamin D in 80 children (42 males, 38 girls) with AH
      and in 86 healthy children without hypercalciuria. A significant difference in
      the ApaI genotype was observed between the AH group and the control group (
      chi(2)=7.21, P=0.027). The AA genotype was associated with a 3.5-fold increased
      risk for idiopathic hypercalciuria compared with the Aa/aa genotype (odds ratio
      3.5, 95% confidence interval 1.1-11). The BsmI and TaqI polymorphisms did not
      show any significant association with AH. Serum osteocalcin levels were
      significantly higher in the group with the AA genotype compared with those with
      the Aa or aa genotype ( P=0.02, P=0.05, respectively). The results indicate that
      the ApaI AA genotype of the VDR gene is not only associated with AH but is also
      related to differences in serum osteocalcin.

PMID- 15141346
TI  - Intravenous cyclophosphamide--resistant systemic lupus erythematosus in Arizona.
AB  - Systemic lupus erythematosus (SLE) tends to be severe and to have a variable
      response in childhood. We undertook this retrospective study to assess response
      rates and outcome in 14 children with SLE. Mean age at onset was 12.8+/-3.1
      years. Ten patients were female and 4 were male, and 12 patients (86%) were
      Hispanic. Creatinine clearance prior to therapy was 104+/-36 ml/min. All had
      hematuria and proteinuria with a protein/creatinine ratio of 3.9+/-4.8. WHO
      classification of renal biopsies revealed class IV in 64%, class III in 21%, and
      class V in 14%. Patients were treated with 6-monthly pulses of intravenous
      cyclophosphamide (IVCY) followed by longer-duration pulses. The mean duration of
      follow-up was 3.7+/-3.3 years. Of the 14 patients, 3 (21%) achieved systemic
      remission but all relapsed subsequently; 7 of 14 achieved renal remission,
      although 6 relapsed. Six (42%) had adverse outcomes, defined by death, dialysis,
      or need for bone marrow transplant. All 6 had failed 6 months of IVCY, suggesting
      that patients who demonstrate resistance to initial IVCY therapy have an
      unfavorable outcome and a high likelihood of complications. In summary, we report
      a poor response to standard therapeutic protocols with higher relapse rates, as
      well as significant adverse outcomes.

PMID- 15141347
TI  - Supernumerary tricentric derivative chromosome 15 in two boys with intractable
      epilepsy: another mechanism for partial hexasomy.
AB  - Rearrangements of chromosome 15q, including isodicentric 15 chromosomes and
      interstitial duplications and triplications, have been previously reported in
      association with autism spectrum disorders. We have identified two boys with
      exceptionally large der(15) chromosomes that are tricentric and contain four
      copies of the proximal long arm, including the Prader Willi/Angelman critical
      region, and leading to hexasomy of the involved segment. Biallelic inheritance of
      maternal alleles and methylation analysis indicate that the markers are
      maternally derived. Clinical assessment of the boys indicated severe cognitive
      impairment associated with marked delays in gross and fine motor skills. Social
      and language deficits were present in both, although the severity of the mental
      retardation precluded diagnosis of autism (both were considered to have pervasive
      developmental disorder-not otherwise specified). Neurologic manifestations
      included infantile spasms evolving into intractable early-onset myoclonic
      seizures, psychomotor regression, and profound diffuse hypotonia. These patients
      represent the most severe end of the spectrum of phenotypes associated with
      segmental aneuploidy for chromosome 15q11-q13.

PMID- 15141350
TI  - [The National Institute for Clinical Excellence (NICE)].
AB  - In discussions on the development of the institutional framework for decisions on
      the benefit package of social health insurance in Germany, the English National
      Institute for Clinical Excellence (NICE) is considered as either a good or a bad
      example for reform. According to this study, the procedures and criteria applied
      by NICE for making health care coverage decisions are legitimate. Procedures are
      transparent and interest groups are broadly represented. Decision criteria
      include cost effectiveness of services - albeit only if information on cost
      effectiveness is available and highly evident. Furthermore, cost effectiveness is
      not the only criteria for coverage decisions. NICE very rarely induces strong
      direct rationing, but rather leaves room for discretion. However, the trade-off
      between maximising allocative efficiency and avoiding distributional consequences
      becomes apparent.

PMID- 15141349
TI  - Estrogen receptor beta (ERbeta) is expressed in brain astrocytic tumors and
      declines with dedifferentiation of the neoplasm.
AB  - PURPOSE: Estrogen receptor beta (ERbeta) is the second identified receptor
      mediating the effects of estrogen on target tissues. The role of ERbeta in cancer
      pathobiology is largely unknown, because specific antibodies have not been
      available until recently. Initial studies have shown that ERbeta expression
      declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a
      synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen
      receptor alpha (ERalpha) and a pure antagonist of ERbeta, has moderate beneficial
      effects in human astrocytic neoplasms. However, most published studies agree that
      glial tumors do not express ERalpha. The purpose of this study was to explore the
      expression of ERbeta in astrocytic neoplasms. METHODS: ERbeta expression was
      monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade
      I-IV) and in adjacent non-neoplastic brain tissue. RESULTS: Moderate or strong
      nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low
      grade astrocytomas, whereas the majority of high-grade tumors were immunonegative
      or displayed weak immunoreactivity. The progressive decline in ERbeta expression
      paralleled the increase in tumor grade. CONCLUSIONS: In as much as ERbeta is
      possibly the only ER expressed in astrocytes, its decreased expression may play
      an important role in astrocytic tumor initiation and in the potential response of
      glial neoplasms to tamoxifen.

PMID- 15141351
TI  - [Prevention before care. Prevention by care].
AB  - BACKGROUND: Maintaining the independence of old people is an issue in the third
      and fourth decade of life determining the quality of life of the elderly. Its
      stabilisation helps to save money in the health care system. However, in the
      debate about efficiency of the German health care system and of the long-term
      care system respectively, aspects of prevention in old age are of subordinate
      importance. In other countries, strategies for avoiding, retarding or moderating
      care are successfully integrated into nursing care prevention. The proposals for
      the further development of the long-term care insurance eliminate these issues to
      a large extent. OBJECTIVE: What are the conditions to establish these
      preventative programmes in the German long-term care system? What should be the
      contents of these programmes? Which have tasks to be done by the nursing
      profession in the future German health and longterm care system? METHOD:
      Systematic search of the Internet and data-bases. Evaluation of the present
      proposals of various commissions concerning the subject. Analysis and evaluation
      of the available approaches in nursing care prevention with regard to their
      conversion to the German care structures. RESULTS: Before the long-term care
      insurance was implemented in Germany in the year 1995 rudiments of long-term care
      prevention existed. These approaches have meanwhile been sacrificed because of
      economic restrictions in the municipalities. In states like Australia, the UK,
      and some Scandinavian countries programmes of nursing care prevention have been
      established as a regular element in the service. CONCLUSIONS: Concepts for
      prevention in the long-term care for old and very old people have been
      implemented quite successfully in several states. In order to employ similar
      programmes in Germany one should refer to available international experience.
      This should be combined with the former experiences in Germany itself.

PMID- 15141352
TI  - [Care required by disabled persons: are official severe disability statistics
      good enough for requirement analyses?].
AB  - The appropriateness of the German Official Severe Disability Statistics for
      determining the amount of care needed by disabled persons is a controversial
      issue and therefore in the focus of this article. The criteria for determining
      the care required by disabled persons are pointed out. Data on prevalence and
      incidence exemplify that Official Severe Disability Statistics is only partially
      appropriate for assessing future care requirements. The problems become
      particularly obvious in topics of data collection, data processing and data
      storage. The deletion of the statistical data at regular intervals of five years
      makes long term prognosis almost impossible. While the problems concerning data
      processing and data storage could be solved by few modifications, the improvement
      of data collection could only be achieved by including and applying the
      International Classification of Functioning (ICF) of the WHO.

PMID- 15141353
TI  - [The problem of response in epidemiological studies in Germany (part I)].
AB  - To achieve high response rates in German epidemiological studies is growing more
      difficult. Low response in epidemiological studies may decrease the acceptance of
      the results. Response, however, is not identical with the quality of a study. In
      the first part of this paper various definitions of response (contact,
      cooperation, response, recruitment proportions) are introduced and discussed in
      the context of different study designs with reference to practical examples. A
      population-based survey such as the Study of Health in Pomerania (SHIP)
      investigates the distribution of risk factors and health-related endpoints.
      Surveys should yield representative results which can be generalised to apply to
      the entire population (external validity). This study design usually requires
      large participitation proportions. In a prospective cohort study such as the
      European Investigation into Cancer and Nutrition (EPIC) the emphasis is on
      internal validity. A stable study population willing to participate in regular
      follow-ups is a primary recruitment goal. If the response in a case-control study
      such as the Northern Germany Leukaemia and Lymphoma Study (NLL) is low, the
      priority is to achieve approximately equal response proportions for cases and
      controls. Simultaneous public relation and media activities can improve
      participitation in a study. Multidimensional strategies combining public
      communications, cooperation with local and regional officials and frequent press
      and media coverage are emphasised. The second part of this paper will discuss
      methods to quantify the effects of the response proportions on the validity of
      the study results.

PMID- 15141354
TI  - [Stalking: problems in differentiation between aberrant social behaviour and
      mental disorders].
AB  - The concept "stalking" refers to willful, malicious, and repeated following or
      harassment of another person that threatens her or his security. Although there
      is nothing new about the occurrence of this conduct it has been discussed in
      psychiatry more intensely in recent years. As a result there are a few attempts
      at classification, without any claim of general validity. Patterns of stalking
      behaviour reflect a wide spectrum from aggressive actions in the course of
      conflicts in a relationship to schizophrenia. Thus, it is not adequate to
      classify this as a psychiatric disorder per se. Thorough diagnostic assessments
      are mandatory before introducing legal measures, whereas if these are omitted,
      the term "mental disorder" may be inappropriately used in a wider sense. This may
      entail unfavourable consequences to be discussed in this paper.

PMID- 15141355
TI  - [AIDS prevention in austrian schools].
AB  - Prevention campaigns and new antiretroviral therapies caused a decline in HIV
      infections as well as mortality from HIV/AIDS in industrialised countries.
      Despite this development AIDS is one of the ten mean causes of death worldwide,
      with 3,1 million deaths in 2002. Hence there is an urgent need for prevention and
      information campaigns, which ideally should start in early childhood or at school
      age. It is well known that preventive strategies start at a time when the risk or
      the possibility of a risky behaviour does not yet exist. A WHO-report in 1993
      showed, that sex education often comes too late, as sexual activity of
      adolescents is already on its way. Persons who are already sexually active can be
      influenced to have fewer sexual partners and to increase safer sex methods. There
      is no evidence for causing a higher risk by sex education of adolescents. In
      Austrian schools numerous experts and organisations cooperate in the sphere of
      sex education and STD-prevention. School children in Vienna are confronted with
      this topic by the schools they attend according to the Sex Education-Act of 1970
      on a voluntary basis. Various examples of effective teaching models prove
      intensive efforts and successful interdisciplinary cooperation. This study
      analyses common risk-reduction-methods and describes the Austrian way of
      HIV/AIDS/STD prevention in school children, although there is no obligation for
      sex education in schools, according to the School Teaching-Act of 1986, which
      leads to better knowledge and subsequent risk behaviour of adolescents in the
      same geographical area.

PMID- 15141356
TI  - [Prevention of dementia (including Alzheimer's disease)].
AB  - Prevention of dementia: Life expectancy still increases linearly, and the elderly
      part of the European population grows rapidly in relation to the young. Dementia,
      however, grows even more rapidly, because it increases exponentially after age
      65; it will become a great burden if nothing is done. The discussion so far is
      concentrated on treatment, whereas prevention is neglected. The therapy of
      dementia, however, has limited effect. Contrary to a widespread opinion
      prevention is possible. Genetic factors alone dominate the fate of cognition only
      in about 3 % of the cases. Besides age, lifestyle and the vascular risk factors
      exercise a great influence. High blood pressure carries a fourfold risk, diabetes
      more than doubles the risk both of the vascular and of the Alzheimer type;
      combined even more. Especially cerebral microangiopathy is strongly associated
      with Alzheimer's dementia, it triggers the vicious circle which leads to amyloid
      deposition. The importance of the circulation is underestimated, because most of
      the microvascular cerebral lesions are not perceived by the patient. All the risk
      factors for Alzheimer's disease after age 65 are also vascular risk factors
      especially for microangiopathy: Apo-E4, oestrogen deficiency, insulin resistance,
      diabetes, arterial hypertension, high cholesterol, old age and increased plasma
      homocystin which is often caused by alcohol consumption even in moderate doses. A
      healthy life style with daily outdoor activity and a Mediterranean diet not only
      reduces the risk of dementia, but also of coronary death and cancer. Cognitively
      stimulating activity protects even more than physical activity against dementia;
      the basis for this is acquired in youth by education. Therapy with statins is
      advisable if atherosclerosis cannot be reasonably counteracted by physical
      activity and diet.

PMID- 15141357
TI  - [Active vaccination current status and required action].

PMID- 15141359
TI  - Use of RNA-arbitrarily-primed PCR to detect the induction of gene expression in
      freshwater bivalves (Unio tumidus) transplanted into the Moselle River.
AB  - RNA-arbitrarily-primed PCR (RAP-PCR) can be used to detect changes in gene
      expression in organisms for which only minimal genomic information is available.
      In this study, RAP-PCR was used to detect modification of mRNA expression in the
      freshwater bivalve Unio tumidus, a mussel commonly used as a sentinel species in
      field studies. RNA expression was analyzed in the digestive glands of mussels
      from a control pond and in mussels transplanted into two sites on the Moselle
      River. The analysis identified a product in all animals exposed to sediments at
      the river station located downstream of a heavily populated area. This product
      was not present in animals exposed at the upstream station or at the control
      site. The additional PCR product was cloned and sequenced, and specific
      oligonucleotides for the sequence were designed to amplify cDNAs from control and
      transplanted mussels. A signal was obtained only with the cDNAs from animals
      exposed at the downstream station, confirming that the variation detected by RAP
      PCR corresponds to an increase of gene expression. Chemical analysis of sediments
      from the control and river sites indicated that the levels of several potential
      pollutants were similar at the three locations and below currently accepted
      pollution thresholds. Our results indicate that RAP-PCR is a sensitive technique
      that can be applied in field studies to identify modifications in the gene
      expression of bioindicator species. This approach can complement chemical,
      biochemical and population studies to assess the impact of human activity on the
      ecological quality of aquatic systems.

PMID- 15141358
TI  - Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.
AB  - Cohen syndrome is an autosomal recessive condition associated with developmental
      delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The
      pleiotropic phenotype, combined with insufficient clinical data, often leads to
      an erroneous diagnosis and has led to confusion in the literature. Here, we
      report the results of a comprehensive genotype-phenotype study on the largest
      cohort of patients with Cohen syndrome assembled to date. We found 22 different
      COH1 mutations, of which 19 are novel, in probands identified by our diagnostic
      criteria. In addition, we identified another three novel mutations in patients
      with incomplete clinical data. By contrast, no COH1 mutations were found in
      patients with a provisional diagnosis of Cohen syndrome who did not fulfill the
      diagnostic criteria ("Cohen-like" syndrome). This study provides a molecular
      confirmation of the clinical phenotype associated with Cohen syndrome and
      provides a basis for laboratory screening that will be valuable in its diagnosis.

PMID- 15141360
TI  - Bacterial and mammalian-cell genotoxicity of mixtures of chlorohydroxyfuranones,
      by-products of water chlorination.
AB  - The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3
      chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy
      2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF)
      and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the
      genotoxicity of the individual compounds. Genotoxicity was evaluated in the
      Salmonella reversion assay (Ames test), the in vitro Chinese hamster ovary (CHO)
      cell Hprt mutation assay, and in the CHO chromosome aberration test. When tested
      individually, the concentrations of the chemicals that were chosen for the
      mixtures induced no or only a modest increase in the genotoxic effects, and
      caused little or no cytotoxicity. In the Ames test, the genotoxic responses
      caused by the mixtures of CHFs did not follow simple additivity. Synergism was
      observed with strains TA97 and TA98, and antagonism with strain TA100. In the
      CHO/Hprt mutation assay, the mutagenic response of the mixtures was inconsistent,
      with near additivity seen with a mixture of CHFs that resulted in 12% cell
      survival. In contrast, the four CHFs together consistently caused more structural
      chromosome damage (mainly chromatid-type breaks and exchanges) compared to the
      sum of net effects of the four CHFs tested alone. Also, a potentiating effect was
      consistently seen for the cytotoxicity of the CHF mixtures both in the CHO/Hprt
      mutation assay and the chromosome aberration test. The present results indicate
      that the genotoxic effects of CHF mixtures can be greater than additive. Such
      effects may be worth considering in the cancer risk assessment of chlorinated
      drinking water.

PMID- 15141361
TI  - Effect of deletion of SOS-induced polymerases, pol II, IV, and V, on spontaneous
      mutagenesis in Escherichia coli mutD5.
AB  - The E. coli dnaQ gene encodes the epsilon subunit of DNA polymerase III (pol III)
      responsible for the proofreading activity of this polymerase. The mutD5 mutant of
      dnaQ chronically expresses the SOS response and exhibits a mutator phenotype. In
      this study we have constructed a set of E. coli AB1157 mutD5 derivatives deleted
      in genes encoding SOS-induced DNA polymerases, pol II, pol IV, and pol V, and
      estimated the frequency and specificity of spontaneous argE3-->Arg(+) reversion
      in exponentially growing and stationary-phase cells of these strains. We found
      that pol II exerts a profound effect on the specificity of spontaneous mutation
      in exponentially growing cells. Analysis of growth-dependent Arg(+) revertants in
      mutD5 polB(+) strains revealed that Arg(+) revertants were due to tRNA suppressor
      formation, whereas those in mutD5 DeltapolB strains arose by back mutation at the
      argE3 ochre site. In stationary-phase bacteria, Arg(+)revertants arose mainly by
      back mutation, regardless of whether they were proficient or deficient in pol II.
      Our results also indicate that in a mutD5 background, the absence of pol II led
      to increased frequency of Arg(+) growth-dependent revertants, whereas the lack of
      pol V caused its dramatic decrease, especially in mutD5 DeltaumuDC and mutD5
      DeltaumuDC DeltapolB strains. In contrast, the rate of stationary-phase
      Arg(+)revertants increased in the absence of pol IV in the mutD5 DeltadinB
      strain. We postulate that the proofreading activity of pol II excises DNA lesions
      in exponentially growing cells, whereas pol V and pol IV are more active in
      stationary-phase cultures.

PMID- 15141362
TI  - DNA damage in peripheral blood lymphocytes of individuals residing near a
      wastewater drain and using underground water resources.
AB  - Mahal is a linear village settlement situated about 0.5 km from an open waste
      water drain, the Tung Dhab drain, which carries effluents from local industrial
      sites. Villagers generally have a low-to-middle socio-economic status and use
      ground water or a combination of ground water and tap water for drinking and for
      their other daily activities. The land in and around Mahal is used for
      agriculture and is irrigated by water from the Tung Dhab. The drain water
      contains heavy metals, and there is a possibility that these and other
      contaminants may reach the ground water table of Mahal and thereby compromise the
      health of the residents. The comet assay was performed on peripheral blood
      lymphocytes from Mahal villagers and revealed statistically significant increases
      in DNA damage as compared to a control group that does not use ground water. DNA
      damage was also significantly related to the age of the villagers and to the
      length of residence in the village. In the absence of other environmental
      exposures, it is concluded that the elevated DNA damage in the villagers is a
      consequence of continuous utilization of contaminated ground water.

PMID- 15141363
TI  - Cytogenetic biomonitoring of Indian women cooking with biofuels: micronucleus and
      chromosomal aberration tests in peripheral blood lymphocytes.
AB  - India currently has the largest number of indoor air pollution-related health
      problems in the world, with three-quarters of its households burning wood,
      cowdung, or crop residues ("traditional" biomass fuels) for cooking, and the
      remainder using kerosene and relatively clean-burning liquefied petroleum gas
      (LPG). Combustion of these fuels produces various pollutants that may cause
      serious health effects in exposed populations. In this study, the micronucleus
      (MN) and chromosomal aberration (CA) assays were used to evaluate the relative
      amounts of DNA damage produced by the use of these cooking fuels. Cytogenetic
      evaluation of 179 female subjects showed a significant increase in both MN and CA
      frequency in blood lymphocytes from users of biomass-fuels in comparison to
      lymphocytes from LPG users (used as a reference population). The relative MN and
      CA frequencies for the users of the various fuels decreased in the order cowdung
      > cowdung/wood >/= wood > kerosene >/= LPG. Further, the results indicated an
      effect of subject age, and the duration of exposure on the MN and CA frequencies
      in biomass fuel users. Age had no significant effects on the genotoxicity
      responses in subjects with </=10 years of exposure to either biomass fuels or
      LPG, but in subjects using biomass fuels for >10 years, CA and MN frequencies
      were higher in older individuals (>30 years of age) than younger subjects.
      Regardless of age, subjects burning biomass fuels had higher MN and CA
      frequencies than LPG users only when exposures were of at least 5 years duration.
      These results indicate that burning biomass-based fuels increases the frequency
      of cytogenetic alterations in blood lymphocytes of exposed populations, possibly
      because of exposure to the various noxious gases and toxic substances present in
      biomass fuels. These cytogenetic markers could be used in the field to assess the
      genotoxic consequences of burning various cooking fuels and for early detection
      of genetic abnormalities in people exposed to various pollutants and toxicants.

PMID- 15141364
TI  - Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in
      the Drosophila Somatic Mutation and Recombination Test.
AB  - Anthracyclines have been widely used as anticancer drugs against different types
      of human cancers. The present study evaluated the mutagenic and recombinagenic
      properties of two anthracycline topoisomerase II (topo II) poisons, daunorubicin
      (DNR) and idarubicin (IDA), as well as the related topo II catalytic inhibitor
      aclarubicin (ACLA), using the wing Somatic Mutation and Recombination Test
      (SMART) in Drosophila melanogaster. The three anthracyclines were positive in
      this bioassay, producing mainly mitotic homologous recombination. The results for
      spot-size distribution and recombinagenic activity indicate that recombinational
      DNA damage accounts for approximately 91, 86, and 62% of DNR, IDA, and ACLA
      genotoxicity, respectively. Besides being a catalytic inhibitor of topo II, ACLA
      is also a topoisomerase I (topo I) poison. This dual topo I and II inhibitory
      effect, associated with its DNA-intercalating activity, could contribute to the
      activity of ACLA in the SMART assay.

PMID- 15141365
TI  - GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human
      lymphocytes.
AB  - Hydroquinone is a myelotoxin that is found in many foods and is also formed
      through the metabolism of benzene. Human exposure to benzene is associated with
      the development of myelodysplastic syndrome and acute myelogenous leukemia.
      Hydroquinone is genotoxic in several in vitro and in vivo test systems, inducing
      micronuclei (MN), sister-chromatid exchange (SCE), and chromosomal aberrations.
      Glutathione S-transferases (GSTs) are a superfamily of polymorphic enzymes
      involved in the conjugation of reactive chemical intermediates to soluble forms.
      These enzymes play a key role in the detoxification of endogenous and exogenous
      compounds, and the polymorphic genes GSTM1, GSTT1, and GSTP1 have been associated
      with the differential metabolism of several genotoxicants. In the present study,
      we have evaluated the effect of GSTM1, GSTT1, and GSTP1 polymorphisms on the
      frequency of MN and SCE induced by hydroquinone in human lymphocytes. Lymphocytes
      were obtained from 15 healthy non-smoking donors, and their GSTM1, GSTT1, and
      GSTP1 genotypes determined. Treatment of cultures of the lymphocytes with
      hydroquinone significantly increased the overall frequencies of MN and SCE
      (P<0.0001). Individuals with the GSTM1 null genotype had a significantly higher
      frequency of MN compared with GSTM1-present individuals (P=0.013); in contrast,
      the GSTM1 genotype had no effect on hydroquinone-induced SCE frequency. The other
      polymorphisms did not significantly affect the frequencies of MN or SCE. These
      results suggest that GSTM1 is involved in the metabolic fate of hydroquinone and
      that polymorphisms in GSTM1 could be related to inter-individual differences in
      DNA damage arising from the exposure to this compound.

PMID- 15141366
TI  - Hprt mutant frequencies in splenic T-cells of male F344 rats exposed by
      inhalation to propylene.
AB  - Propylene is a major industrial intermediate and atmospheric pollutant to which
      humans are exposed by inhalation. In this study, 6-week-old male F344 rates were
      exposed to 0, 200, 2000, or 10,000 ppm propylene by inhalation for 4 weeks (6
      h/day, 5 days/week), and mutant frequencies were determined in the Hprt gene of
      splenic T-lymphocytes. Twenty milligrams of cyclophosphamide monohydrate (CPP)/kg
      bw, given on the penultimate day of propylene exposure, was used as a positive
      control mutagen. Rats (n = 8/group) were necropsied for isolation of T-cells 8
      weeks after the last dose, a sampling time that produced peak spleen Hprt mutant
      frequencies (Mfs) in a preliminary mutant manifestation study using CCP
      treatment. Hprt Mfs were measured via the T-cell cloning assay, which was
      performed without knowledge of the animal treatment groups. Mean Hprt Mfs were
      significantly increased over control values (mean Mf = 5.24 +/- 1.55 (SD) x 10(
      6)) in CPP-treated rats (10.37 +/- 4.30 x 10(-6), P = 0.007). However, Hprt Mfs
      in propylene-exposed rats were not significantly increased over background, with
      mean Mfs of 4.90 +/- 1.84 x 10(-6) (P = 0.152), 5.05 +/- 3.70 x 10(-6) (P =
      0.895), and 5.95 +/- 2.49 x10(-6) (P = 0.500) for animals exposed to 200, 2000,
      or 10,000 ppm propylene, respectively. No significant increase in F344 rat or
      B6C3F1 mouse cancer incidence was reported in the National Toxicology Program
      carcinogenicity studies of propylene across this same exposure range. Taken
      together, these findings support the conclusion that inhalation exposure of rats
      to propylene does not cause mutations or cancer.

PMID- 15141368
TI  - Efficacy of a smoking-cessation intervention for elective-surgical patients.
AB  - We tested an intervention to help smokers abstain (fast) from smoking before
      surgery, maintain abstinence postoperatively, and achieve long-term cessation. A
      randomized experiment included 237 patients admitted for presurgical assessment
      who smoked. The intervention included counseling and nicotine replacement
      therapy. Treatment group participants (73.0%) were more likely to fast than were
      controls (53.0%): chi(2)(1, N = 228) = 8.89, p =.003, and more likely to be
      abstinent 6 months after surgery (31.2% vs. 20.2%). There was no significant
      difference in the abstinence rates at 12 months after surgery, chi(2)(1, N = 169)
      <.001, p = 1.00. Encouraging patients to fast from smoking before surgery and
      postoperative support are efficacious ways to reduce preoperative and immediate
      post-operative tobacco use.

PMID- 15141369
TI  - Severity of fecal incontinence in community-living elderly in a health
      maintenance organization.
AB  - An anonymous survey containing questions about the severity of fecal incontinence
      (FI)--frequency, amount, and type--and its correlates was distributed to
      community-living elderly at four managed-care clinics. Completed surveys were
      received from 1,352 respondents whose mean (+/-standard deviation) age was 75 +/-
      6 years and 60% of whom were female. Approximately 19% reported having FI one or
      more times within the past year. Incontinence that soiled underwear or was of
      loose or liquid consistency was most common. More frequent FI and a greater
      amount of FI were significantly associated with loose or liquid stool
      consistency, defecation urgency, bowel surgery, and chronic health conditions.
      Therapies aimed at normalizing stool consistency or reducing urgency may be
      beneficial in lessening FI severity.

PMID- 15141371
TI  - Relationships of sexual imposition, dyadic trust, and sensation seeking with
      sexual risk behavior in young Urban women.
AB  - This study was designed to examine the relationships of sexual imposition, dyadic
      trust, and sensation seeking with HIV sexual risk behavior in 257 young urban
      women. Interviews were conducted using Audio Computer-Assisted Self-Interview
      (ACASI). Hierarchical multiple regression revealed that sexual imposition, dyadic
      trust, and sensation seeking explained 18.3% of the variance in sexual risk
      behavior. Although sexual imposition was positively related to sexual risk,
      pressure to satisfy a male partner sexually was more common than physical
      coercion. Dyadic trust was negatively related, indicating that women engaged in
      sexual risk behavior with men they distrusted. Sensation seeking was positively
      related to sexual risk. Findings suggest the need for enhancing awareness of non
      sexually imposing relationship alternatives and incorporating thrill and
      excitement in health promotion messages.

PMID- 15141370
TI  - Indomethacin and ibuprofen preserve gastrocnemius muscle mass in mice bearing the
      colon-26 adenocarcinoma.
AB  - Skeletal muscle wasting is a prominent feature of cancer cachexia and involves
      decreased muscle protein synthesis and increased activity of the ubiquitin
      proteasome pathway of protein degradation. We report that both indomethacin and
      ibuprofen improved body weight and weight of the gastrocnemius muscle in tumor
      bearing mice. Ibuprofen increased the soluble protein content of the muscle
      without affecting muscle levels of phosphorylated p70 S6 kinase, a ribosomal
      kinase involved in protein synthesis. Paradoxically, indomethacin increased
      levels of ubiquitin-conjugated proteins. Further study is needed to understand
      the mechanism of action by which indomethacin and ibuprofen preserve body weight
      and muscle mass in the tumor-bearing mice. The data suggest that ibuprofen may
      have beneficial effects in the treatment of cancer cachexia.

PMID- 15141372
TI  - Psychometric evaluation of the Chinese version of the State Anxiety Scale for
      Children.
AB  - The assessment of anxiety in children undergoing surgery must be addressed before
      any intervention can be appropriately planned, provided, and evaluated. The
      purpose of this study was to evaluate the psychometric properties of the Chinese
      version of the State Anxiety Scale for Children. Two hundred and thirty-seven
      children from a primary school and 112 children admitted for day surgery were
      recruited for this study. The instrument demonstrated adequate internal
      consistency reliability, appropriate concurrent validity, and construct validity.
      Factor analyses further confirmed the construct validity of the scale, with a
      good fit between the factor structure of the scale and the observed data. Results
      suggest that the Chinese version of the State Anxiety Scale for Children can be
      used as a self-report assessment tool in measuring the anxiety level of Chinese
      children ages 7-12 years.

PMID- 15141373
TI  - Instrument development of the Self-Efficacy Scale for Abused Women.
AB  - The development of a scale to measure an abused woman's self-efficacy is
      described. The Self-Efficacy Scale for Abused Women (SESAW) originally was a 27
      item 100-mm visual analog scale. It underwent face and content validity testing
      and was administered to a community sample of abused women (N = 50). The SESAW
      was tested for internal consistency, test-retest reliability, and construct
      validity. Cronbach's alphas were.95 and.96 at times 1 and 2, respectively. The
      bivariate correlation between the SESAW at times 1 and 2 was r =.85, p <.01.
      Construct validity was established by a moderate bivariate correlation with the
      criterion as measured by the Self-Efficacy Scale-general/global subscale (r =.64,
      p <.01 at time 1, and r =.78, p <.01 at time 2). The SESAW was streamlined to 19
      items. The SESAW is an acceptable measure of situation-specific self-efficacy in
      community-based abused women.

PMID- 15141374
TI  - A multistep model for ovarian tumorigenesis: the value of mutation analysis in
      the KRAS and BRAF genes.
AB  - Epithelial ovarian tumours represent a complex group of histological subtypes and
      there has long been controversy over the question of a precursor lesion for these
      neoplasms. The application of mutation analysis of the KRAS and BRAF genes
      (members of the RAS-RAF-MEK-ERK-MAP kinase pathway) is consistent with the model
      for progression of mucinous carcinomas and a subset of serous carcinomas (the so
      called low-grade serous carcinomas) through benign and borderline lesions. The
      relatively high incidence of BRAF and KRAS mutations in serous borderline tumours
      and low-grade serous carcinomas, and their extremely low incidence/absence in
      high-grade serous carcinomas, provide strong evidence that high-grade carcinomas
      do not arise through this intermediate step.

PMID- 15141375
TI  - Using tissue adjacent to carcinoma as a normal control: an obvious but
      questionable practice.
AB  - When carcinoma tissue is investigated using biochemical, immunohistochemical, and
      genetic techniques, adjacent tissue that is macroscopically normal is frequently
      used as a control, since cancer-related pheno- and geno-typic alterations are
      assumed to be absent. However, a field that contains genetically abnormal cells
      surrounds a significant proportion of carcinomas (for example, over 30% of head
      and neck cancers). These fields can be large (>7 cm in diameter) and consist of
      cells that are clonally related to the carcinoma. This indicates that adjacent
      epithelium must be checked for genetic abnormalities before it is considered
      normal and used as a control for comparison with carcinoma.

PMID- 15141376
TI  - Organ distribution of severe acute respiratory syndrome (SARS) associated
      coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus
      transmission pathways.
AB  - We previously identified the major pathological changes in the respiratory and
      immune systems of patients who died of severe acute respiratory syndrome (SARS)
      but gained little information on the organ distribution of SARS-associated
      coronavirus (SARS-CoV). In the present study, we used a murine monoclonal
      antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV
      RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization,
      respectively, to detect SARS-CoV systematically in tissues from patients who died
      of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine,
      distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas,
      adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen,
      lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus
      or muscle. These results suggest that, in addition to the respiratory system, the
      gastrointestinal tract and other organs with detectable SARS-CoV may also be
      targets of SARS-CoV infection. The pathological changes in these organs may be
      caused directly by the cytopathic effect mediated by local replication of the
      SARS-CoV; or indirectly as a result of systemic responses to respiratory failure
      or the harmful immune response induced by viral infection. In addition to viral
      spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and
      sweat glands may be excreted via faeces, urine and sweat, thereby leading to
      virus transmission. This study provides important information for understanding
      the pathogenesis of SARS-CoV infection and sheds light on possible virus
      transmission pathways. This data will be useful for designing new strategies for
      prevention and treatment of SARS.

PMID- 15141377
TI  - Tissue distribution of ACE2 protein, the functional receptor for SARS
      coronavirus. A first step in understanding SARS pathogenesis.
AB  - Severe acute respiratory syndrome (SARS) is an acute infectious disease that
      spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has
      been identified as the aetiological agent of SARS. Recently, a metallopeptidase
      named angiotensin-converting enzyme 2 (ACE2) has been identified as the
      functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in
      virtually all organs, its protein expression is largely unknown. Since
      identifying the possible route of infection has major implications for
      understanding the pathogenesis and future treatment strategies for SARS, the
      present study investigated the localization of ACE2 protein in various human
      organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine,
      colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain).
      The most remarkable finding was the surface expression of ACE2 protein on lung
      alveolar epithelial cells and enterocytes of the small intestine. Furthermore,
      ACE2 was present in arterial and venous endothelial cells and arterial smooth
      muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in
      humans in the epithelia of the lung and small intestine, which might provide
      possible routes of entry for the SARS-CoV. This epithelial expression, together
      with the presence of ACE2 in vascular endothelium, also provides a first step in
      understanding the pathogenesis of the main SARS disease manifestations.

PMID- 15141378
TI  - Expression of Fhit, cell adhesion molecules and matrix metalloproteinases in
      atypical adenomatous hyperplasia and pulmonary adenocarcinoma.
AB  - Invasive parenchymal-type lung adenocarcinoma develops from atypical adenomatous
      hyperplasia (AAH), through an intermediate in situ stage of bronchioloalveolar
      carcinoma (BAC). We examined the expression of the putative tumour suppressor
      gene product Fhit, cell adhesion molecules CD44v6, E-cadherin and beta-catenin,
      and matrix metalloproteinase 2 and its inhibitor, TIMP-2, in a range of AAH
      lesions, BACs and invasive adenocarcinomas, to determine the changes in molecular
      expression associated with this form of neoplastic progression. Sections of
      formalin-fixed wax-embedded archival tissue were stained by standard
      Immunohistochemical techniques and scored semi-quantitatively, resulting in a
      grading of negative/low- or high-level staining. Fhit protein was retained at
      high levels in over 90% of AAH and 83% of BAC, but was found in only 6% of
      stromally invasive tumours (p < 0.0001). CD44v6 staining was high-level in 64% of
      AAH but fell to 26% in stromally invasive tumour (p = 0.007). E-cadherin and beta
      catenin showed the opposite, with more high-level staining as adenocarcinoma
      developed (p < 0.001). High-level MMP-2 and TIMP-2 expression was relatively
      infrequent in AAH (32% and 40% respectively), rose in BAC (89% each) but fell in
      stromally invasive tumour (31% and 17% respectively) (p < 0.01). Unlike in
      central bronchial carcinogenesis, loss of Fhit expression is a relatively late
      event in this putative progression of lung adenocarcinogenesis, and has potential
      as a surrogate marker of invasion, which could be of value in screening patients
      for lung cancer. Loss of CD44v6 expression follows the convention of falling
      adhesion molecule expression as malignancy develops. Increased expression of E
      cadherin and beta-catenin may reflect increased cell-cell contact as tissue
      architecture changes in the transition from AAH to adenocarcinoma. Loss of MMP-2
      and TIMP-2 in stromally invasive tumour may reflect a particular role for MMP-2
      at the BAC stage, with later down-regulation of this particular enzyme.

PMID- 15141379
TI  - CK20 expression, CDX2 expression, K-ras mutation, and goblet cell morphology in a
      subset of lung adenocarcinomas.
AB  - There are data in the literature that suggest a close relationship between the
      expression of CK20 and CDX2, K-ras mutations, and goblet cell morphology. The
      present study has examined these factors in a cohort of 264 non-small cell lung
      cancers. Thirteen of 212 adenocarcinomas expressed CK20; 29 expressed CDX2; K-ras
      mutation was identified in 28; and goblet cell features were present in 19. These
      four factors correlated with each other in a complex way and therefore a logistic
      regression model was constructed. Significant correlations were found between
      CK20 and CDX2 expression, and between K-ras mutation and goblet cell morphology,
      and there was a marginal correlation between CDX2 immunoreactivity and goblet
      cell morphology. These four features have also been commonly detected in
      colorectal, pancreato-biliary, and ovarian mucinous carcinomas, suggesting that
      these adenocarcinomas may be prototypical, independent of the organ of origin.
      Furthermore, as high and uniform expression of CDX2 was characteristic of
      metastatic colorectal cancer, weak and/or focal CDX2 expression should alert
      surgical pathologists to the possibility of primary lung adenocarcinoma,
      especially in the presence of goblet cell morphology. However, some lung
      adenocarcinomas may express CDX2 strongly: in this case, CK20 also tends to be
      positive.

PMID- 15141380
TI  - Matrix proteoglycans and remodelling of interstitial lung tissue in
      lymphangioleiomyomatosis.
AB  - The interstitial lung disease lymphangioleiomyomatosis (LAM) is characterized by
      diffuse proliferation of smooth muscle cells (SMCs), which in many patients show
      TSC2 (tuberin) gene mutations, in addition to thickening of interstitial tissues,
      loss of alveoli, and the development of cystic spaces. While SMC proliferation is
      the defining feature of LAM, a significant proportion of LAM lung tissue consists
      of expanded interstitial connective tissue that is negative for smooth muscle
      actin and TSC2 mutations. The importance of this actin-negative interstitial
      tissue to the pathophysiology of LAM is not clear. The present study has
      determined the contribution of this interstitial tissue to LAM lung volume by
      morphometric analysis and has examined its cell and matrix proteoglycan
      composition by immunohistochemistry. Lung tissue from nine LAM patients and four
      control subjects was examined. LAM lung contained twice as much interstitial
      tissue as control lung (27% versus 13% of total lung volume), with SMCs
      accounting for less than 25% of the interstitial volume. Areas of interstitial
      tissue stained strongly for the matrix proteoglycans versican and biglycan.
      Decorin was prominent in association with collagen bundles. SMCs did not stain,
      or stained lightly, for proteoglycans. Versican and biglycan deposits were
      closely associated with actin-negative interstitial fibroblasts identified by
      prolyl 4-hydroxylase immuno-staining. Comparatively normal alveolar walls in LAM
      lung also stained strongly for versican and had a reduced elastin content.
      Thickened interstitial regions contained significant amounts of elastin
      (approximately 13% of interstitial volume) but with fibres in disorganized
      patterns. Elastic fibres were absent from areas that stained strongly for
      versican and biglycan. These areas also showed weak staining for elastin binding
      protein (EBP), consistent with proteoglycan-induced shedding of EBP and
      inhibition of elastic fibre formation. These findings point to a significant
      contribution from matrix proteoglycans to the expanded and remodelled
      interstitial lung tissue of LAM patients.

PMID- 15141381
TI  - Expression of luminal and basal cytokeratins in human breast carcinoma.
AB  - We have examined basal and luminal cell cytokeratin expression in 1944 cases of
      invasive breast carcinoma, using tissue microarray (TMA) technology, to determine
      the frequency of expression of each cytokeratin subtype, their relationships and
      prognostic relevance, if any. Expression was determined by immunocytochemistry
      staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and
      the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth
      muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast
      majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a
      differentiated glandular phenotype, a finding associated with good prognosis, ER
      positivity and older patient age. In contrast, basal marker expression was
      significantly related to poor prognosis, ER negativity and younger patient age.
      Multivariate analysis showed that CK 5/6 was an independent indicator for relapse
      free interval. We were able to subgroup the cases into four distinct phenotype
      categories (pure luminal, mixed luminal/basal, pure basal and null), which had
      significant differences in relation to the biological features and the clinical
      course of the disease. Tumours classified as expressing a basal phenotype (the
      combined luminal plus basal and the pure basal) were in a poor prognostic
      subgroup, typically ER negative in most cases. These findings provide further
      evidence that breast cancer has distinct differentiation subclasses that have
      both biological and clinical relevance.

PMID- 15141382
TI  - Co-expression of neuregulins 1, 2, 3 and 4 in human breast cancer.
AB  - We have produced antibodies to the NRG2-alpha, NRG2-beta, NRG3 and NRG4 proteins
      and used these, and previously described antibodies to NRG1-alpha and NRG1-beta,
      to detect expression of each ligand by immunocytochemical staining in a series of
      45 breast cancers. Each protein was expressed in a proportion of cases.
      Statistical analysis suggested that expression of one factor was associated with
      a high probability that other members of the family were co-expressed. NRG2-alpha
      expression was associated with node positivity (p-value = 0.005). The mRNAs for
      NRG1, 2, 3 and 4 were found in established breast cancer cell lines and NRG1, 2
      and 3 mRNAs were detected in primary breast cancers. Expression of NRG4 mRNA was
      shown by in situ hybridization in sections from primary breast cancers. This data
      demonstrates that each member of the NRG family of ligands is expressed in breast
      cancer and suggests that they may be involved in regulating cell behaviour.

PMID- 15141383
TI  - Model of the early development of diffuse gastric cancer in E-cadherin mutation
      carriers and its implications for patient screening.
AB  - Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome caused, in
      30-40% of cases, by germline mutations of the E-cadherin/CDH1 gene. The presence
      of clinically undetectable early gastric cancers has been previously reported in
      ten of ten prophylactic gastrectomies from germline E-cadherin mutation carriers.
      In the present study, detailed maps of the distribution of invasive cancers in
      nine of these ten stomachs were produced and precursor lesions of HDGC searched
      for. The nine gastrectomy specimens contained from 1 to 161 foci of early diffuse
      gastric cancer, occupying 0.005-2.96% of the gastric mucosa. Seven specimens
      contained focal in situ signet ring carcinoma. Pagetoid spread of signet ring
      cells was observed beneath the epithelial lining of gastric foveolae/glands.
      Helicobacter pylori organisms and associated pathology were absent from all
      cases. Two-dimensional maps of the gastrectomy specimens revealed lesions
      throughout the gastric mucosa without evidence of antral clustering. The
      distribution and size of the cancers in the gastrectomy specimens indicate that
      standard endoscopic screening with random or geographically targeted biopsies is
      unlikely to provide sufficiently sensitive clinical screening for at-risk
      individuals. An in situ precursor of signet ring carcinoma was identified and a
      model for neoplastic progression in the setting of HDGC is proposed.

PMID- 15141384
TI  - Up-regulation of MDA-BF-1, a secreted isoform of ErbB3, in metastatic prostate
      cancer cells and activated osteoblasts in bone marrow.
AB  - Prostate cancer (PCa) has a propensity to metastasize to bone. The identification
      of molecules that mediate the biological interactions between PCa cells and the
      bone environment is crucial to the understanding of PCa bone metastasis. The
      present study has used protein purification to identify bone metastasis-related
      factors present in bone marrow aspirates from PCa patients with bone metastasis.
      MDA-BF-1 was the first bone metastasis factor to be identified and is a secreted
      isoform of the ErbB3 growth factor receptor. To determine which cell types in PCa
      bone metastases express MDA-BF-1, MDA-BF-1 expression was studied in both primary
      and metastatic PCa cells, using an antibody to the extracellular domain (Ab10)
      and another to the cytoplasmic domain (RTJ.2) of ErbB3 to distinguish MDA-BF-1
      from p180-ErbB3. It was found that epithelial cells in primary PCa did not
      express MDA-BF-1. In contrast, epithelial cells in 41 of 45 PCa metastases (18 of
      19 lymph node metastases and 23 of 26 bone metastases), and activated osteoblasts
      in bone metastases, expressed MDA-BF-1. In addition, newly formed bone matrices
      adjacent to activated osteoblasts were also immunopositive for MDA-BF-1,
      suggesting that activated osteoblasts secrete MDA-BF-1. These observations
      indicate that MDA-BF-1 is up-regulated in metastatic PCa and raise the
      interesting possibility that MDA-BF-1 may play a role in the metastasis and
      progression of PCa, particularly in bone.

PMID- 15141385
TI  - Expression of the Epstein-Barr virus (EBV)-encoded latent membrane protein 2A
      (LMP2A) in EBV-associated nasopharyngeal carcinoma.
AB  - The Epstein-Barr virus (EBV) is associated with virtually all cases of
      undifferentiated nasopharyngeal carcinoma (NPC) and has been classified as a
      group I carcinogen. In addition to its potential role in the pathogenesis of NPC,
      EBV also provides a possible target for immunotherapy of NPC, since a limited
      number of viral genes are expressed in the neoplastic cells. The EBV-encoded
      latent membrane protein 2A (LMP2A) is considered a promising target since it
      provides epitopes recognized by EBV-specific T-cells. Using immunohistochemistry,
      the present study shows that LMP2A is expressed at the protein level in the
      neoplastic cells of 16 of 35 (45.7%) NPC biopsies. This finding provides further
      evidence suggesting that NPC tumour cells may be susceptible to lysis by
      cytotoxic T-cells directed against LMP2A and should encourage efforts to develop
      immunotherapeutic approaches for the treatment of NPC.

PMID- 15141386
TI  - Haemangiomas are formed by cells expressing high levels of alphavbeta3 integrin
      and lacking acetylated LDL uptake.
AB  - Haemangiomas are benign tumours occurring in up to 12% of Caucasians,
      particularly in infancy and childhood. In the present study, two variant cell
      lines were isolated from murine endothelioma cells. One variant, named
      t.End.1V(high), represented 16.9% of the parental cell population and was
      selected by virtue of high expression levels of integrin alphavbeta3 and reduced
      capacity to endocytose acetylated low-density lipoproteins (Ac-LDLs). A second
      variant, named t.End.1V(low), represented 38.8% of the parental endothelioma cell
      line, expressed low levels of alphavbeta3 integrin, and was able to endocytose Ac
      LDL. These phenotypic modifications were stable and correlated with specific
      morphological and functional properties of the two variant cell lines. While the
      t.End.1V(high) cells induced the formation of large haemangiomas when injected
      subcutaneously into mice, the t.End.1V(low) cells formed haemangiocytomas. When
      compared with t.End.1V(low) cells, the t.End.1V(high) cells showed increased
      migratory capacity, lacked an inflammatory response, and formed cord-like
      structures in fibrin gels. In contrast, the t.End.1V(low) cells organized into
      cysts with a lumen in fibrin gels. They rarely formed blood-filled haemangiomas
      in vivo and recruited host smooth muscle cells, a phenomenon typical for vessel
      wall maturation of resting cells. These data suggest that Ac-LDL uptake and the
      level of alphavbeta3 integrin expression are linked to the ability of endothelial
      cells to form large haemangiomas in vivo.

PMID- 15141388
TI  - Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor
      (PDGF) play a central role in the pathogenesis of digital clubbing.
AB  - Digital clubbing is associated with many unrelated serious diseases but its
      pathogenesis remains a clinical enigma. It has been hypothesized that platelet
      clusters impacting in the distal vasculature mediate the morphological changes of
      clubbing. Since the multifunctional cytokines vascular endothelial growth factor
      (VEGF) and platelet-derived growth factor (PDGF) are released on platelet
      aggregation and are hypoxically regulated, the present study has examined their
      role in clubbing using immunohistochemistry. Basic fibroblast growth factor
      (bFGF), transforming growth factor-beta 1 (TGF-beta1), microvessel density,
      carbonic anhydrase IX (CAIX), hypoxia inducible factor (HIF)-1alpha, and HIF
      2alpha were also measured. There was a significant increase in VEGF (p = 0.01),
      pKDR (p = 0.03), PDGF (p = 0.017), and HIF-1alpha and HIF-2alpha (p = 0.004 and p
      = 0.004, respectively) expression together with a significant increase in
      microvessel density (p = 0.03) in the stroma in clubbed digits compared with
      controls. There was no difference in CAIX (p = 0.25), TGF-beta1 (p = 0.66) or
      bFGF (p = 0.18) between affected and control groups. These findings suggest that
      VEGF and PDGF are released after platelet impaction and that their expression is
      hypoxically enhanced in the stroma after capillary occlusion. VEGF may synergize
      with PDGF in inducing the stromal and vascular changes present in digital
      clubbing.

PMID- 15141387
TI  - Basic fibroblast growth factor promotes apoptosis and suppresses granulation
      tissue formation in acute incisional wounds.
AB  - Cytokines are thought to play an important role in cellular loss and apoptosis
      during the repair of granulation tissue. In order to investigate the role of
      apoptosis following the administration of basic fibroblast growth factor (bFGF)
      to a wound, the present study examined the relationship between the degree of
      granulation tissue formation and the level of apoptosis in rat skin incisional
      wounds, following treatment with an intradermal injection of bFGF (0.1 microg and
      1 microg per cm of wound). Histological assessment of the width of the wound
      tissue showed that the degree of granulation tissue in the 1 microg-bFGF-treated
      group had increased by day 7, but then subsequently diminished by days 14 and 28.
      The TUNEL index increased rapidly from day 1, peaking on day 7, with the index
      being higher in the 1 microg-bFGF-treated group on days 4, 7, and 14, when
      compared with a control group. In parallel with a marked increase in the TUNEL
      index over the first 14 days, the number of cells positive for vimentin and CD3
      in the 1 microg-bFGF-treated wounds had decreased by day 14. The number of PCNA
      positive cells, an indicator of cell proliferation, peaked on day 4 in the bFGF
      treated wounds and then declined rapidly. On the basis of these results, it is
      suggested that the suppression of granulation tissue formation in bFGF-treated
      wounds is mainly due to an early and persistent increase in apoptosis in the
      granulation tissue cells. The expression of both transforming growth factor (TGF)
      beta1 and bFGF was also elevated in the bFGF-treated wounds on days 4 and 7,
      suggesting that fibroblast apoptosis was induced by bFGF treatment. Unexpectedly,
      on day 28, the wound breaking strength was not reduced in the bFGF-treated
      wounds. These results indicate that apoptosis regulation following bFGF
      administration to an incisional wound may lead effectively to granulation tissue
      formation and promote a scar-less repair process.

PMID- 15141389
TI  - Re: To KF, Tong JH, Chan PK, et al. Tissue and cellular tropism of the
      coronavirus associated with severe acute respiratory syndrome: an in-situ
      hybridization study of fatal cases. J Pathol 2004; 202: 157-163.

PMID- 15141392
TI  - A new instrument to assess participant motivation for involvement in preventive
      interventions.
AB  - The Nijmegen Motivation List for Prevention (NML-P) is a new instrument to assess
      the motivation of participants for involvement in preventive group interventions.
      The aim of the current study was to explore the underlying dimensions of the NML
      P and the predictive potential of the instrument for those participating in a
      psychoeducational preventive group intervention for depression: the Coping with
      Depression course. Principal component analyses revealed four components:
      readiness to participate, social support, doubt, and burden. Preliminary
      prediction analyses showed doubt, support, and burden to be related to the
      outcome of the depression prevention intervention.

PMID- 15141391
TI  - A need for ethnic similarity in the therapist-patient interaction? Mediterranean
      migrants in Dutch mental-health care.
AB  - Evidence concerning a preference for ethnic matching in the therapist-patient
      dyad and the effects of ethnic matching on treatment satisfaction is equivocal.
      This study examined the importance of ethnic similarity in mental-health care in
      the Netherlands. A convenience sample of 82 Turkish and 58 Moroccan outpatients
      in the community mental-health care was interviewed. Quantified data were
      analyzed using multivariate techniques. The majority of the respondents did not
      value ethnic matching as important; clinical competence and compassion were
      considered to be more relevant than ethnic background. An ethnically dissimilar
      therapist treated the majority of the outpatients. Outpatients treated by a
      native Dutch therapist reported similar satisfaction with the services provided
      as those treated by an ethnically similar therapist. According to Turkish and
      Moroccan outpatients in Dutch mental-health care, ethnic matching is not
      considered to be preferential nor essential for treatment satisfaction. Other
      health-care characteristics such as empathy, expertise, and sharing of worldview
      are considered to be as important.

PMID- 15141393
TI  - Psychological mindedness and cognitive style.
AB  - Psychological mindedness (PM) is theorized to be a cognitively toned personality
      variable, yet, there is a paucity of research addressing the cognitive components
      of PM. This study was intended to redress this issue by testing the empirical
      associations between PM and Ambiguity Tolerance, as measured by the Revised Scale
      for Ambiguity Tolerance (MacDonald, 1970); Locus of Control, as measured by the
      Locus of Control Scale (Rotter, 1966); and Magical Thinking, as measured by the
      Magical Ideation Scale (Eckblad & Chapman, 1983). The results indicated that PM
      is positively associated with ambiguity tolerance, whereas it is inversely
      related to external locus of control and magical thinking. These findings suggest
      a cognitive style profile for PM that includes flexibility, a sense of personal
      agency, and a propensity for realistic thinking. High-PM individuals are likely
      to bring these cognitive resources to bear in psychotherapy, a tendency that
      might explain why high PM patients make better use of treatment.

PMID- 15141394
TI  - Effect of patient sex, clinician sex, and sex role on the diagnosis of Antisocial
      Personality Disorder: models of underpathologizing and overpathologizing biases.
AB  - This study examined the influence of patient sex and clinician sex and sex role
      for a case, meeting minimum diagnostic criteria for Antisocial Personality
      Disorder, in which patient sex was varied. The purpose was to provide an in-depth
      evaluation of the process by which patient sex and characteristics of clinicians
      may contribute to bias in personality disorder diagnoses. Psychologists (N = 167)
      read two cases, including the target case, and provided symptom ratings and
      diagnoses. A sex-unspecified condition served as a baseline to assess for over-
      and underpathologizing bias, and diagnoses based on the symptom ratings were
      compared to assigned diagnoses. Clinician sex role was assessed using the Bem Sex
      Role Inventory-Short Form. Results revealed that bias occurred when the patient's
      sex (female) was inconsistent with the gender weighting of the symptoms in the
      case (masculine), but the direction of the bias was consistent with sex roles
      (underdiagnosis of sex-role-inconsistent diagnoses, overdiagnosis of sex-role
      consistent diagnoses). Path models of over- and underdiagnostic bias were
      developed using structural equation modeling. Patient sex had a direct effect on
      diagnostic ratings whereas clinician sex role had an indirect effect through
      symptom ratings.

PMID- 15141396
TI  - Assessing compliance with homework assignments: review and recommendations for
      clinical practice.
AB  - Despite the emphasis of homework assignments in psychotherapy research and
      practice, methods to assess homework compliance have been relatively neglected.
      This article presents a brief review of 32 studies that described the assessment
      of homework compliance, and evaluated homework compliance in relation to
      treatment outcome. More than half of the studies relied on a single source of
      compliance data (n = 23), eight studies involved retrospective accounts, and only
      four studies used the same measure of homework compliance. The vast majority of
      studies focused on the assessment of "homework compliance" without consideration
      of the "quality of homework completion" or other key factors. A more
      comprehensive framework for homework compliance is discussed, and a new Homework
      Rating Scale (HRS) is proposed as the first step towards assisting the field in a
      more reliable and valid assessment of homework compliance.

PMID- 15141395
TI  - An interactive-synergetic approach to the assessment of personality vulnerability
      to depression: Illustration using the adolescent version of the Depressive
      Experiences Questionnaire.
AB  - Research on personality vulnerability to depression is characterized by a "main
      effect" approach, often at the expense of examining interactions among various
      dimensions of vulnerability. To compare the "main effect" and "interactive
      synergetic" approaches, we utilized data from a longitudinal study of adolescent
      adjustment. Focusing on dependency, self-criticism, and efficacy, the three
      factors of the adolescent version of the Depressive Experiences Questionnaire
      (DEQ; Blatt, Schaffer, Bers, & Quinlan, 1992), we found support for the
      interactive-synergetic approach. Dependency and self-criticism interacted in
      predicting changes in depressive and internalizing symptoms (under low efficacy),
      and among boys-changes in internalizing and externalizing symptoms. Results
      illuminate the synergetic interplay among dimensions of risk and resilience in
      clinical research and practice.

PMID- 15141397
TI  - The MMPI-2 in sexual harassment and discrimination litigants.
AB  - In order to understand patterns of respondents on validity and clinical scales,
      this study analyzed archival Minnesota Multiphasic Personality Inventory 2s (MMPI
      2s) produced by 192 women and 14 men who initiated legal claims of ongoing
      emotional harm related to workplace sexual harassment and discrimination. The
      MMPI-2s were administered as a part of a comprehensive psychiatric forensic
      evaluation of the claimants' current psychological condition. All validity and
      clinical scale scores were manually entered into the computer, and codetype and
      cluster analyses were obtained. Among the women, 28% produced a "normal limits"
      profile, providing no MMPI-2 support for their claims of ongoing emotional
      distress. Cluster analysis of the validity scales of the remaining profiles
      produced four distinctive clusters of profiles representing different approaches
      to the test items.

PMID- 15141398
TI  - Therapist affirmation and the process and outcome of psychotherapy: two
      sequential analytic studies.
AB  - Therapist affirmation was examined in two studies, the first with cognitive
      behavioral therapy (CBT, N = 22) and the second with time-limited dynamic
      psychotherapy (TLDP, N = 20). Affirmation was identified using Structural
      Analysis of Social Behavior (SASB), and sequential analysis used to gauge its
      impact on therapy process and outcome. It was hypothesized that affirmation would
      correspond with patients' continuation of the current topic of conversation, but
      relate negatively to outcome if generally offered after maladaptive statements.
      Patients in Study 1 (CBT) were more likely to continue a topic after it was
      affirmed, and affirmation of maladaptive statements reliably differentiated
      patients who evidenced clinically significant change from those who did not at
      termination and at 12-months posttreatment. Affirmation of maladaptive statements
      in Study 2 (TLDP) corresponded with poorer outcome in relationships with
      significant others, but unexpectedly with improvements in self-concept.

PMID- 15141399
TI  - A pilot study of a yoga and meditation intervention for dementia caregiver
      stress.
AB  - Twelve older female dementia patient family caregivers (eight Latinas and four
      Caucasians) participated in a six-session manualized yoga-meditation program
      (called Inner Resources) designed to help caregivers cope with stress. Pre/post
      comparisons revealed statistically significant reductions in depression and
      anxiety and improvements in perceived self-efficacy. Average minutes of weekly
      yoga-meditation practice were significantly associated with improvements in
      depression. The majority of caregivers found the intervention useful and reported
      subjective improvements in physical and emotional functioning. These findings
      suggest that Inner Resources may be a feasible and effective intervention for
      family caregivers and may improve affect, coping, physical well-being, and stress
      management.

PMID- 15141400
TI  - Relationships among attention deficit hyperactivity disorder, induced labor, and
      selected physiological and demographic variables.
AB  - We investigated whether events associated with physiological maternal and fetal
      stress during the birth process were associated with diagnosis of attention
      deficit hyperactivity disorder (ADHD), alone or in combination with demographic
      variables. We gathered data through maternal responses to a 17-item
      questionnaire. Sex, mother's educational level, mother's age at delivery,
      interval between the beginning of labor and birth, and presence or absence of
      complications during the delivery process accounted for 42% of the variance in
      the diagnostic (ADHD) category. The model correctly classified 87% of the non
      ADHD group (n = 90) and 48% of the children with ADHD (n = 40), for an overall
      correct classification rate of 75%. A differential effect for sex was indicated,
      but a low number of females in the diagnostic category limited meaningful
      analysis. Maternal age at delivery and maternal education level emerged as the
      strongest predictors, with the exception of sex, of ADHD in the full model.

PMID- 15141401
TI  - Obstetric epidural and chronic adhesive arachnoiditis.

PMID- 15141402
TI  - Anaesthesia for spinal surgery in adults.

PMID- 15141403
TI  - The patient as a surgical assistant.

PMID- 15141404
TI  - Accuracy of methods to estimate ionized and "corrected" serum calcium
      concentrations in critically ill multiple trauma patients receiving specialized
      nutrition support.
AB  - BACKGROUND: The purpose of this study was to determine the accuracy of 22
      published methods to estimate serum ionized calcium (iCa) and "corrected" total
      serum calcium (totCa) concentrations in critically ill, multiple trauma patients.
      Seven of these formulas estimated iCa and 15 were directed toward predicting a
      "corrected" totCa. METHODS: Adult patients admitted to the trauma intensive care
      unit who received specialized nutrition support were consecutively recruited for
      study. Patients who received blood products, i.v. calcium, or therapeutic doses
      of heparin within 24 hours before the laboratory measurements or had a history of
      cancer, bone disease, parathyroid disease, hyperphosphatemia (> or = 6 mg/dL),
      hyperbilirubinemia (> 3.5 mg/dL), or renal failure requiring dialysis were
      excluded. The 22 published methods were analyzed for sensitivity, specificity,
      percentage false negatives, and percentage false positives for predicting
      hypocalcemia or hypercalcemia. RESULTS: One hundred patients were studied 4.9 +/-
      3.3 days postinjury and were receiving enteral nutrition (n = 81), parenteral
      nutrition (n = 18), or both (n = 1) at the time of study. Twenty-one patients
      were hypocalcemic (iCa < or = 1.12 mmol/L) and 6 were hypercalcemic (iCa > or =
      1.32 mmol/L). The mean sensitivity of the 22 methods for assessing hypocalcemia
      was 25% +/- 32% and the specificity was 90% +/- 18%. Although the average
      percentage of false positives for assessing hypocalcemia was 10% +/- 18%, the
      mean percentage of false negatives was inordinately high at 75% +/- 32%. The most
      common method for determination of "corrected" totCa concentration ["corrected"
      calcium = totCa + (0.8 x (4-serum albumin concentration))] had a sensitivity of
      only 5%. The McLean-Hastings nomogram method, the most common method for
      estimating serum iCa concentration, had a sensitivity of 67% but unfortunately
      also had a significant false-positive rate of 27%. Serum totCa correlated
      modestly with iCa (r2 = .334, p < .001). Those patients with a serum albumin < or
      = 2 g/dL (n = 43) had a significantly higher prevalence of hypocalcemia than
      those with a higher serum albumin concentration (37% incidence of hypocalcemia vs
      10%, respectively, p < .002). CONCLUSIONS: Aberrations in calcium homeostasis are
      frequent (27%) in postresuscitative critically ill multiple trauma patients.
      Methods for predicting hypocalcemia lack sensitivity and are often associated
      with an unacceptable rate of false negatives. Predictive methods for estimating
      ionized or corrected serum concentrations should not be used. Direct measurement
      of serum iCa concentration is indicated for assessing calcium status for this
      population.

PMID- 15141405
TI  - Liver function and plasma antioxidant status in intensive care unit patients
      requiring total parenteral nutrition: comparison of 2 fat emulsions.
AB  - BACKGROUND: Efficacy and safety of an alpha-tocopherol-enriched emulsion
      incorporating soybean, coconut, olive, and fish oils (SMOF) are compared in terms
      of biologic parameters to those of soybean oil-based emulsion (LIPOVEN). METHODS:
      Twenty stressed patients were randomly assigned in a double-blind study to
      receive at least a 5-day course of total parenteral nutrition. Plasma activities
      of liver enzymes, C-reactive protein, antioxidant capacity, alpha-tocopherol,
      retinol, and low density lipoprotein (LDL)-alpha-tocopherol levels were
      determined. LDL-lipid oxidation is measured after incubation of the LDL in the
      presence of a prooxidant. RESULTS: The plasma activities of liver enzymes and the
      phospholipids/apo A1 ratio were increased in both groups. However, in the SMOF
      group the increases were lower than in the LIPOVEN group and non-significant for
      the CRP plasma level and the alanineamino-transferase activity. Before parenteral
      nutrition, the plasma antioxidant status was markedly reduced in both groups.
      After parenteral nutrition discontinuation, the antioxidant capacity and the
      amount of LDL-derived oxidation by-products formed were comparable in both
      groups. There was a significant improvement in plasma lipophilic antioxidant
      vitamins and LDL-alpha-tocopherol levels only in the SMOF group. CONCLUSIONS: The
      lower increase of plasma liver enzymes and phospholipids/apo A1 ratio in the SMOF
      group suggest a better liver function than in the LIPOVEN group. This beneficial
      effect results in a higher liver mobilization and plasma levels of lipophilic
      antioxidants. They could, together with higher delivery of omega-3 fatty acids to
      peripheral tissues, contribute positively to survival rate of stressed patients.

PMID- 15141406
TI  - Effect of i.v. dextrose administration on glucose metabolism during surgery.
AB  - BACKGROUND: The inhibitory influence of exogenous dextrose on glucose production
      has been shown to be less pronounced during injury and sepsis. This protocol was
      designed to investigate the effect of i.v. hypocaloric dextrose on glucose
      metabolism during elective abdominal surgery. METHODS: Fourteen patients with
      rectal cancer were studied under fasting conditions and toward the end of a 3
      hour infusion of dextrose (2 mg.kg-1 per minute) either in absence (control
      group, n = 7) or presence of colonic surgery (surgery group, n = 7). Endogenous
      glucose production was determined by using primed continuous infusions of [6,6
      2H2]glucose before and during dextrose administration. We also measured the
      plasma concentrations of glucose, lactate, cortisol, glucagon, and insulin.
      RESULTS: The administration of dextrose decreased the endogenous glucose
      production in all patients (p < .05). This decrease was less pronounced during
      surgery (p < .05). Plasma glucose concentration increased during dextrose
      infusion in both groups (p < .05), with higher values in the surgery group than
      in the control group (p < .05). Plasma concentrations of lactate and glucagon
      remained unaltered. Dextrose infusion increased the plasma insulin concentrations
      to the same extent in both groups (p < .05). Cortisol plasma levels increased
      only in the surgery group (p < .05). CONCLUSIONS: Surgical stress blunts the
      inhibitory effect of i.v. dextrose on endogenous glucose production.

PMID- 15141407
TI  - A randomized trial of endoscopic and fluoroscopic placement of postpyloric
      feeding tubes in critically ill patients.
AB  - BACKGROUND: Early postpyloric feeding is considered the accepted method of
      nutrition support in critically ill patients. Endoscopic and fluoroscopic
      techniques are associated with the highest percentage of successful placement.
      The purpose of this study was to compare endoscopic vs fluoroscopic placement of
      postpyloric feeding tubes in critically ill patients. METHODS: This is a
      randomized prospective clinical trial. Forty-three patients were randomized to
      receive feeding tubes by endoscopic or fluoroscopic technique. All procedures
      were performed at the bedside in the critical care unit. A soft small-bore
      nonweighted feeding tube was used in all cases. Successful placement was
      confirmed by either an abdominal x-ray for endoscopic technique or a fluoroscopic
      radiograph for fluoroscopic technique. RESULTS: Postpyloric feeding tubes were
      successfully placed in 41 of 43 patients (95%). The success rate using endoscopic
      technique was 96% (25 of 26), whereas the rate using fluoroscopy was 94% (16 of
      17). The average time of successful placement was 15.2 +/- 2.9 (mean +/- SEM)
      minutes for endoscopic placement and 16.2 +/- 3.2 minutes for fluoroscopic
      placement, which was not statistically significant (p > .05). CONCLUSIONS:
      Endoscopic and fluoroscopic placement of postpyloric feeding tubes can safely and
      accurately be performed at the bedside in critically ill patients. Our results
      showed no significant difference in the success rate or time of placement between
      endoscopic vs fluoroscopic placement of postpyloric feeding tubes.

PMID- 15141408
TI  - 3-0 methylglucose uptake as a marker of nutrient absorption and bowel length in
      pediatric patients.
AB  - BACKGROUND: Inert carbohydrate probes are commonly used to assess intestinal
      permeability; we have previously shown that the actively transported moiety 3-0
      methylglucose (3-0 MG) is a useful marker of intestinal surface area and nutrient
      absorption in animal models of short bowel syndrome (SBS). This study examines
      the correlation of 3-0 MG absorption with nutrient absorption, bowel length, and
      the tolerance of enteral feeds in pediatric patients. METHODS: Fifteen children
      (1 month to 15 years in age) were studied after intestinal surgery. All had a
      stoma, 2 were > 1 year of age, the remainder had surgical intervention as a
      neonate or within the first month of life. Eight had SBS (50% expected bowel
      length for age). Bowel length was measured intraoperatively. Nutrient absorption
      was quantified with a 48-hour bowel study, measuring fat, protein, and
      carbohydrate output directly. 3-0 MG absorption and intestinal permeability were
      quantified using a solution containing 30 mg/mL 3-0 MG, 20 mg/mL mannitol and 30
      mg/mL lactulose (osmolarity 352, given at 1 mL/kg via feeding tube). Subsequent
      urine production was collected for 8 hours, and probe recovery measured using
      HPLC. RESULTS: 3-0 MG absorption was significantly correlated with nutrient
      absorption. The correlation with protein absorption was r2 = .59, fat r2 = .62
      and carbohydrate r2 = .56. The correlation between 3-0 MG absorption and bowel
      length was r2 = .58. 3-0 MG absorption was significantly lower in SBS patients vs
      patients with normal bowel length (15.8 +/- 6.7 vs 30.5 +/- 10.2%). 3-0 MG
      absorption also correlated with the ability to tolerate enteral feeds (r2 = .38;
      p < .03 for all comparisons). CONCLUSIONS: 3-0 MG may be a useful marker of
      nutrient absorption and bowel length in pediatric patients with short bowel
      syndrome. The simplicity and reproducibility of the method make it an attractive
      option for following patient outcomes. Further studies are suggested to determine
      the utility of these markers in directing the clinical management of patients.

PMID- 15141409
TI  - Endotoxin and cytokine released during parenteral nutrition.
AB  - BACKGROUND: Apart from its benefits, parenteral nutrition (PN)-related
      complications have been reported. Studies have shown that PN could alter
      cytochrome P450 (CYP) activity. One of the possible mechanisms is through
      cytokine and nitrite release, which is triggered by endotoxin. The purpose of
      this study is to investigate the potential release of endotoxin, cytokines, and
      nitrite during PN. METHODS: Rats were randomly assigned into either (a) the PN
      group, which received continuous PN infusion only; or (b) the control group,
      which received normal chow with saline infusion. The infusions were administered
      continuously for 7 days, and then blood was collected and microsomes were
      prepared from the excised livers. RESULTS: Endotoxin levels in the PN group were
      significantly higher in portal vein but not in inferior vena cava when compared
      with those of the controls. TNF-alpha and IL-6 levels were significantly higher
      in the PN group (p < .05). However, IL-1 beta levels were not significantly
      different in the 2 groups (p > .05). The nitrite levels, the end product of
      nitric oxide formation, were found to be almost 2 times higher after PN (p <
      .05). CONCLUSIONS: It is confirmed that a 7-day infusion treatment of PN in rat
      may be linked to bacterial translocation, which leads to increased levels of
      endotoxin. This increase could trigger cytokine release, which could down
      regulate CYP activities.

PMID- 15141410
TI  - Effects of enteral feeding on antroduodenal motility in healthy volunteers with 2
      different fiber-supplemented diets: a 24-hour manometric study.
AB  - BACKGROUND: Antroduodenal motility during enteral nutrition remains poorly
      understood. The aim of the study was to evaluate antroduodenal motor activity
      during intermittent intragastric feeding and between enteral solutions
      supplemented with new recommended soluble or standard insoluble fibers. METHODS:
      Two 24-hour antroduodenal manometric studies were performed with a interval of 1
      week in 8 healthy volunteers. Two similar enteral diets except for fiber (soluble
      vs insoluble) were separately assessed in random order at 2 intervals (lunch and
      dinner) for 2 hours each. Phase III was studied during three 6 hour-periods
      (after lunch, after dinner, and at night). The other quantitative manometric
      parameters were studied before (1 hour), during (2 hours), and after (2 hours)
      lunch and dinner. RESULTS: During the 2-hour postinfusion period, phase III
      reoccurred in 14 cases during the day and in 16 cases during the night. Phase III
      was always interrupted during feeding, which reoccurred in 14 cases during the 2
      hour postinfusion period and in 16 cases during the after-dinner period.
      Nocturnal phase III was more frequent, lasted longer, with a lower amplitude than
      the diurnal phase. Addition of either soluble or insoluble fiber did not appear
      to have an influence on phase III or on the antroduodenal motor activity.
      CONCLUSIONS: Intragastric feeding interrupted phase III at the antroduodenal
      stage during infusion but was correlated with interdigestive motility.
      Antroduodenal motility did not significantly change either during or after
      intragastric feeding. The addition of either soluble or insoluble fiber does not
      seem to have an influence on gastroduodenal motor response to intermittent
      intragastric feeding.

PMID- 15141411
TI  - Education and evidence are needed to improve neonatal parenteral nutrition
      practice.
AB  - BACKGROUND: Parenteral nutrition (PN) is an essential component of neonatal care
      for those infants who are unable to tolerate adequate enteral feeding. Its use is
      not without complications such as biochemical derangements, sepsis, thrombosis,
      extravasation of fluid, and death. Such complications can be reduced by
      meticulous management of PN in response to biochemical abnormalities, nutrition
      teams, policies to reduce sepsis, and staff training to be more aware of
      pericardial and pleural effusions. We ascertained the current practices in PN
      administration and management of complications in all neonatal units with 6 or
      more intensive care cots in England, Scotland, and Wales. METHODS: Telephone
      survey of middle grade doctors (Specialist Registrars) working in all 57 neonatal
      units was conducted using a standard questionnaire. The questions were focused
      around practical issues and problems that are commonly encountered with PN
      practice, including composition, complications, and nutrition support. RESULTS: A
      response was obtained from 95% of the units contacted and a wide range of
      practices observed. Thirty-three percent of units delay protein (nitrogen) until
      > 48 hours after birth. Lipid infusions are stopped in proven or suspected sepsis
      in just over half of all units. In hyperglycemic preterm infants, 25 units
      decrease their glucose infusion, 21 commence insulin, and 8 have no policy. Two
      thirds of middle grade doctors had no idea of the amount of protein or nitrogen
      to prescribe for these infants, and only one-third involve a pharmacist in the PN
      prescribing. CONCLUSIONS: There is a diverse practice and knowledge with a
      concerning lack of education in nutrition among the middle grade doctors in
      England, Scotland, and Wales. The management of common complications such as
      sepsis and hyperglycemia are highly variable. Improved staff training and
      production of unified evidence-based guidelines need urgent consideration.

PMID- 15141412
TI  - Pump-assisted enteral nutrition can prevent aspiration in bedridden percutaneous
      endoscopic gastrostomy patients.
AB  - BACKGROUND: Vomiting, aspiration, and pneumonia are serious side effects in
      enteral feeding via percutaneous endoscopic gastrostomy (PEG), which often leads
      to hospitalization. To this day, it has not been proven whether pump-assisted
      (PA) or gravity-controlled application is the safer method for long-term feeding
      via PEG in bedridden patients. METHODS: This study was conducted as a
      prospective, randomized crossover study. Fifty bedridden PEG patients were fed
      using the pump-assisted method (G1) and 50 patients were fed using the gravity
      controlled feeding method (G2). After 6 weeks of observation (O1), the feeding
      methods in both groups were switched, followed by another 6 weeks of observation
      (O2). Daily recording was done using a standardized questionnaire. The glucose
      levels during O1 and O2 were determined on days 1, 21, and 42. RESULTS: The
      patients in both groups were compatible in age, sex, and medical illness. By
      comparing G1 and G2, a significantly lower regurgitation rate (p < .0002),
      vomiting of feeding substrate (p < .009), aspiration (p < .01), and pneumonia (p
      < .02) was observed. The diarrhea rate in G2 was higher than in G1 (p < .007).
      The glucose profiles in G1 showed a significantly better development (p < .0007)
      than the ones in G2. After switching the application method in G2, the PA group
      (now G2) showed a significantly improved rate of regurgitation, vomiting,
      aspiration, and diarrhea and improved glucose profiles. CONCLUSION: Feeding via
      PA shows improved safety, which is documented in a lower rate of diarrhea,
      regurgitation, vomiting, and aspiration. PA also noted a more effective glucose
      metabolization, which results in better glucose levels. As a result of this
      prospective study, pump-assisted feeding is recommended for bedridden patients
      requiring long-term feeding via PEG.

PMID- 15141413
TI  - Nutrition support in Brazil: past, present, and future perspectives.
AB  - The history of nutrition support in Brazil is parallel to its development in the
      world. Inspired by the publications of the surgical group headed by Professor
      Rhoads at the University of Pennsylvania, a group of Brazilian physicians
      pioneered the beginning of parenteral nutrition (PN) therapy. The Brazilian
      Society of Parenteral and Enteral Nutrition (SBNPE) was officially founded in
      1975. Soon, scientific contributions started to appear, reflected by articles in
      the Journal of Parenteral and Enteral Nutrition and other journals and by books.
      In many states of Brazil, nutrition support services were created to carry out
      scientific and educational activities. The relationship with the American Society
      of Parenteral and Enteral Nutrition was fundamental in the development of
      clinical nutrition in Brazil because of the strong scientific exchange between
      the United States and Brazil. However, after the stimulating initial launching,
      momentum slowed because of the lack of medical awareness and inadequate
      reimbursement. In Brazil, the federal government is responsible for the majority
      of health care, but enteral nutrition was not reimbursed. In response to this
      situation, a study in 4000 hospitalized patients was undertaken in Brazil. It was
      reported that nearly half of them presented with malnutrition, and > 12% had
      severe malnutrition. These alarming results were decisive in persuading the
      Brazilian government to begin reimbursement for enteral nutrition. Today,
      Brazilian hospitals that assist public health system patients receive
      reimbursement for enteral nutrition. However, it is required to have an
      officially registered nutrition support team and a certified and approved
      facility for enteral feeding preparation. Considering that low nutrition
      prescription in Brazil could be the result of lack of nutrition education (not
      required in most medical schools), the SBNPE participated in the creation of 2
      very effective, practical, and dynamic courses for the basic teaching of clinical
      nutrition. These courses were created by the Latin American Federation of
      Parenteral and Enteral Nutrition: the TNT (Total Nutrition Therapy) Course and
      the CINC Course (Interdisciplinary Course in Clinical Nutrition). These 2 courses
      are available to members of all Latin American countries and are regularly
      offered by the SBNPE to its members all over Brazil. Altogether, > 4000
      physicians, dietitians, nurses, and pharmacists have been introduced to the basic
      principles and practice of clinical nutrition. It is clear that the outstanding
      ideas of Professors Rhoads, Dudrick, and Wilmore and other collaborators from
      this group in the field of clinical nutrition have grown and flourished in
      Brazil.

PMID- 15141415
TI  - Where have all the beds gone?

PMID- 15141414
TI  - Immunonutrition in critically ill patients.

PMID- 15141416
TI  - [Renal xenotransplantation from hDAF pig to baboon. Experience and review].
AB  - The renal xenotransplant could be the solution on the demand of organs for
      transplantation. We present here our experience and review the actual status of
      the xenotransplant. METHODS: We have done 20 xenotransplants from transgenic pig
      h DAF to baboons, with four protocols of immunosuppression. All the hosts were
      treated with GAS 914. Group A: Cyclophosphamide, Cyclosporine, Mycophenolate, and
      Steroids (n = 10). Group B: Cyclophosphamide, Cyclosporine, FTY 720, and Steroids
      (n = 3). Group C: Basiliximab, Cyclosporine, Mycophenolate, and Steroids (n = 3).
      Group D: Basiliximab, FTY 720, Everolymus, and Steroids (n = 4). RESULTS: The
      duration of the xenografts ranged between 1 and 31 days. The function of the
      xenografts in relation to the type of immunosuppression were not significantly
      different: A) 7 days, B) 8 days, C) 8 days, and D) 9 days. CONCLUSIONS: 1. The
      cold ischemic time of the graft, has influence in the initial function of the
      kidneys but not in the evolution and duration of the graft. 2. The hyperacute
      rejection has been overcome with the utilization of transgenic pigs. The graft
      failure was due to acute humoral rejection that was not aborted by the actual
      inmunosupressors. 3. It is necessary to develop new immunosuppression protocols,
      through new knowledge of their pharmacology and the physiology of the xenografts,
      and at the same time it is important to avoid the potential risk of transmission
      of animal infections.

PMID- 15141417
TI  - [Vasectomy: study of 300 interventions. Review of the national literature and of
      its complications].
AB  - OBJECTIVES: The aims of this paper are: 1. To study the demand and reasons why of
      the vasectomy in area 12 of Valencian Community. 2. To analyse the adverse
      effects of our series and the predictable risk factors. 3. To review the adverse
      effects in the national series. 4. To review the adverse effects referred to in
      international publications. PATIENTS AND METHODS: A retrospective study was made
      of 300 patients who had submitted themselves to a vasectomy between january 1992
      and december 2000. All the clinical dossiers were reviewed according to 10 pre
      established variables. age, number of offspring, reasons why, pre-vasectomy
      anticontraceptives; date of operation, type of anaesthesia used, pathologic
      anatomy, semen analysis after vasectomy, adverse effects and their possible
      causes (risk factors). The basic statistic study was done using a data base of
      Microsoft Access and the interpretations of the different variables using a table
      of Excel. RESULTS: The demand for contraceptive attention (vasectomy) is the 8th
      cause for external urological consulting and the 4th for urological local
      ambulatory surgery of our area. 300 operations were done during that period. The
      average age of the patients was 37.5 years old (ranging from 25 to 51). The
      number of offspring ranged from 1 to 7, with a promedia of 2.41 children/patient.
      The reasons why were: voluntary family planning (86%), medical illnesses of the
      female which contraindicated gestation (9%), genetic reasons (4.33%) and social
      sanitary problems (0.66%). Contraceptive methods used by 71.63% are known: The
      widest-used method being IUD (49.74%) and the preservative (25.88%). 30 patients
      (10%) had adverse effects, 29 patients having light adverse effects. The most
      frequent were: 12 orchiepididymitis (4%), 5 spermatic granulomas (1.66%), 3
      chronic scrotal pain (1%), 2 scrotal haematoma (0.66%) and 2 bleeding (0.66%).
      There was one serious complications and of all the cases mentioned above only one
      needed hospitalization (impetigo-sepsis) and another needed surgery due to a
      spermatic granuloma. There were no pregnancies or post-vasectomy court cases. 81%
      of the patients had been declared azoospermic within 45 to 60 days after the
      vasectomy in one or two consecutive semen analysis. CONCLUSIONS: The vasectomy is
      a safe and simple way for male sterilization. It's the most widely done urologic
      operation in Spain. The technique isn't extent of adverse effects (0 to 18%) and
      its seriousness varies from a simple ecchymosis to Fournier's gangrene,
      endocarditis or sepsis. A doctor would be considered negligent if he/she didn't
      inform the patient about the remote possibility of a spontaneous recanalisation
      of the vas deferens leading to renewed fertility (failure of the vasectomy). It
      is imperative to give post-vasectomy information where the patient must continue
      using his habitual anticonceptive method until the azoospermia shown in 2 semen
      analysis confirm the sterility of the patient so that the urologist has no legal
      problem.

PMID- 15141418
TI  - [Histopathologic validation of the tissue-microarray technology of urothelial
      cancer. Our experience].
AB  - INTRODUCTION: The array technology offers: a big advance to clinic and basic
      investigator, it provides a variety of technics (immunohistochemistry, FISH,
      proteomics) to understand the molecular mechanisms of cancer. It offers scale
      economy in reagents versus the conventional methods. Array most be ratified
      because the sample is so reduced. MATERIAL AND METHODS: 52 consecutive cases have
      been chosen from paraffin blocks of bladder and ureteral cancer which are 5-7
      years old, a tissue array has been made; disks have been arranged in lines and
      columns, in an aleatory way, in order to guide it's reading. It has been
      evaluated by a pathologist with any relation to specimen selection. RESULTS: 87
      sheets ha been obtained. Number 1 has been dyed with HE. Has been discrepancy in
      27% of sample's stage. Has not been a discrepancy in histopathologic diagnostic.
      There is no sample's representation in 11 points (17%). DISCUSSION: Our results
      offer good results in sample's validation. The sample's antigenicity of tissue is
      conserved. Array sample's represent a 97%, similarly to all unit of conventional
      sections of the specimen.

PMID- 15141419
TI  - [Mutations of the androgen receptor gene in patients with clinically localized
      adenocarcinoma of the prostate].
AB  - The aim of this study was to detect mutations in the human androgen receptor gene
      in radical prostatectomy specimens. MATERIAL AND METHODS: The genomic sequence
      was realized in 67 radical prostatectomy specimens. The mean age was 64 years
      old. The PSA median was 15 ng/ml. TNM 1997: 34.3% were T1 and 65.7% T2. Genomic
      sequence: 1. Radical prostatectomy specimens desparaffitation. 2. Extraction of
      the DNA 3. DNA amplification. 4. Automatic genome sequence. 5. Comparison with
      Gene-Bank. RESULTS: 16.7% of the specimens were mutated. The most frequent
      mutation was the punctual mutation. The exon most frequent mutated was exon 1.

PMID- 15141421
TI  - [Calcified retroperitoneal liposarcoma].
AB  - Case report of a retroperitoneal liposarcoma pleomorfico with calcification in
      diagnosed in our hospital. We comment on its clinical characteristics, diagnostic
      methods and treatment. We likewise comment the possible differential diagnoses.

PMID- 15141420
TI  - [Surgery of large residual mass after chemotherapy in advanced testicular germ
      cell tumor].
AB  - Treatment for testicular tumours has progress in such a manner in the last years
      that high cure percentages can at present be achieved. After chemotherapy, in
      most cases, residual mass can appear. In this cases surgery is considered a
      viable therapeutic option although it implies an advanced surgical training since
      it is a complex technique and implies serious implications. We submit the case of
      a patient who presented a large residual mass from a testicular germ cell tumour
      after being treated with orquiectomia and chemotherapy. Surgery was performed
      resulting in total and radical extirpation of residual mass.

PMID- 15141422
TI  - [Secondary vesical amyloidosis].
AB  - The bladder involvement is a very unusual fact in systemic amyloidosis. The
      distinction of primary and systemic amyloidosis disease with bladder involvement
      (secondary bladder amyloidosis) is important to the urologist. Secondary
      amyloidosis of the bladder is a rare disease entity (approximately 20 cases
      published). We document a case of a woman with a large history of rheumatoid
      arthritis who developed severe macrohematuria. Diagnosis was done by biopsy that
      revealed amyloidosis, and it was confirmed with an immunohistochemical staining
      of the specimens that defined the process as amyloid AA (secondary amyloidosis).

PMID- 15141423
TI  - [Adult polycystic disease in horseshoe kidney].
AB  - A case report of kidney polycystic and horseshoe kidney coincidence in the same
      patient. They are two congenital associated renal diseases uncommon for
      urologists. The form of clinic presentation is described, the diagnostic methods
      used and the therapeutic management.

PMID- 15141424
TI  - [Paratesticular rhabdomyosarcoma].
AB  - Contribution of one case of paratesticular rhabdomyosarcoma in a 10-years old
      male patient. Following radical orchiectomy it was classified as Group Ia
      (Intergroup Rhabdomyosarcoma Study). Treatment was completed with 9
      polychemotherapy courses of Ifosfamide, Vincristine and Actinomicine D. The
      patient was disease-free 6 months after the treatment.

PMID- 15141425
TI  - [Pyeloureteral duplicity and intrathoracic kidney].
AB  - Intrathoracic ectopia is an unusual ectopia that represents less than 5% of renal
      ectopia. The association of a duplex system and an intrathoracic renal ectopia is
      very rare. We report a case of a girl affected from these two anormalities, being
      the first case published in the literature reviewed. Presentation, diagnosis and
      therapeutic aspects are discussed.

PMID- 15141426
TI  - [Duloxetine and other tricyclic antidepressive agents: pharmacodynamic effects in
      the lower urinary tract].

PMID- 15141427
TI  - Dietary calcium and dairy modulation of adiposity and obesity risk.
AB  - Dietary calcium plays a key role in the regulation of energy metabolism and
      obesity risk. This appears to be mediated primarily by dietary calcium modulation
      of circulating calcitriol, which in turn regulates adipocyte intracellular
      calcium ([Ca2+]i). Increased [Ca2+]i stimulates lipogenic gene expression and
      activity and inhibits lipolysis, resulting in increased adipocyte lipid
      accumulation. Since calcitriol stimulates adipocyte Ca2+ influx, low calcium
      diets promote adiposity, while dietary calcium-suppression of calcitriol reduces
      adiposity. These concepts are confirmed in controlled rodent studies as well as
      by epidemiological and clinical trial data, all of which confirm protection from
      obesity with high calcium intakes. Moreover, dairy sources of calcium exert
      markedly greater effects which are most likely attributable to additional
      bioactive compounds in dairy which act synergistically with calcium to attenuate
      adiposity.

PMID- 15141428
TI  - Monounsaturated fatty acid intake by children and adults: temporal trends and
      demographic differences.
AB  - Epidemiologic evidence suggests that dietary monounsaturated fatty acids (MUFA)
      may have a beneficial health effect. Twenty-four-hour dietary intake data
      collected on 10-year-olds from 1978 to 1994 and on children and adults (ages 0-30
      years) were examined for time, age, gender, ethnic, and geographic location
      differences in MUFA intake. Children's percent energy from MUFA decreased
      significantly from 1978 (14.1%) to 1994 (11.9%) with intake of oleic acid
      decreasing from 33.9 g/day (1973) to 25.7 g/day (1994). In 1994-96, percent
      energy from MUFA was 13% for children and adults aged 12 to 30 years, with 5%
      from palmitoleic acid and 93% from oleic acid. Males and blacks had significantly
      higher MUFA intake across all age groups than females and whites. Intakes of MUFA
      increased from 0 to 11 years of age to young adulthood (12-19 years), with no
      further increase at 20 to 30 years of age. Intakes of MUFA were lowest in the
      Northeast and highest in the Midwest. There were differences in food sources of
      MUFA by age group. For children 0 to 5 years of age, major sources were whole
      milk, peanut butter, 2% milk, and French fries; for children 6 to 11 years of
      age, major sources were whole milk, peanut butter, French fries, and 2% milk; for
      children 12 to 19 years of age, French fries, salt snacks, whole milk, and meat
      pizza were the major sources; for adults, French fries, whole milk, potato chips,
      and ground beef were the most common sources of MUFA. U.S. children and adults
      displayed temporal trends and demographic differences in intakes and food sources
      of MUFA. The implications of these changes and differences on biologic risk
      factors for specific chronic diseases warrant further investigation.

PMID- 15141429
TI  - Micronutrients and cancer therapy.
AB  - The effect of micronutrient supplementation on the effectiveness of cancer
      chemotherapeutic agents is reviewed, and the efficacy of antioxidants, folic
      acid, and other vitamins and minerals is discussed. Although some micronutrients
      show promise in enhancing the cytotoxicity of anticancer agents in vitro, caution
      should be exercised in recommending micronutrient supplementation for cancer
      patients receiving chemotherapeutic drugs. To date, few well-controlled clinical
      trials have been conducted to evaluate the efficacy of micronutrients in
      promoting the sensitivity of tumors to chemotherapeutic agents.

PMID- 15141430
TI  - Does environmental exposure to manganese pose a health risk to healthy adults?
AB  - Manganese is an essential nutrient that also may be toxic at high concentrations.
      Subjects chronically exposed to manganese-laden dust in industrial settings
      develop neuropsychological changes that resemble Parkinson's disease. Manganese
      has been proposed as an additive to gasoline (as a replacement for the catalytic
      properties of lead), which has generated increased research interest in the
      possible deleterious effects of environmental exposure to manganese. Low-level
      exposure to manganese has been implicated in neurologic changes, decreased
      learning ability in school-aged children, and increased propensity for violence
      in adults. However, a thorough review of the literature shows very weak cause-and
      effect relationships that do not justify concern about environmental exposure to
      manganese for most of the North American population.

PMID- 15141431
TI  - Beverage consumption and risk of obesity among Native Americans in Arizona.
AB  - Native Americans face some of the highest rates of obesity and diabetes in the
      world. Despite numerous education programs to reduce obesity among Native
      Americans, little attention has been paid to reducing fructose, particularly in
      the form of high-fructose corn syrup in beverages. Considerable data indicate
      that energy from beverages does not displace energy from other foods throughout
      the day, often leading to energy imbalance, and numerous studies have documented
      that beverages are a leading contributor to energy intakes among Native
      Americans. Prevention programs that target pregnant women and parents of infants
      and very young children are necessary to halt the epidemic of obesity among
      Native Americans; one approach may be by promoting sugar-free beverages.

PMID- 15141432
TI  - Executive summary: conference on Dietary Supplement Use in the Elderly-
      proceedings of the conference held January 14-15, 2003, Natcher Auditorium,
      National, Institutes of Health, Bethesda, MD.
AB  - Several issues prompted the need for this conference. Among these were the
      reported high prevalence (> 50%) of use of supplements among individuals over 50
      years of age, inadequate scientific evidence supporting the safety and benefits
      of use among these individuals, and a report issued by the General Accounting
      Office (GAO) in 2001. This GAO report entitled "Health Products for Seniors:
      'Anti-Aging' Products Pose Potential for Physical and Economic Harm," arose from
      concerns among legislators that seniors were spending money from their limited
      incomes on products that were not only ineffective but also potentially harmful.
      The conference was organized around three sessions to address the issues
      highlighted above, which were usage of dietary supplements among the elderly, age
      related changes and issues that affect the use of supplements, and the evidence
      base supporting the use of supplements in disease prevention and health
      maintenance. Each session was followed by a panel discussion. This Executive
      Summary is organized around the three major discussion topics. The summary does
      not explicitly follow the order of the conference presentations; rather it is
      intended to capture and examine the current research gaps in knowledge and
      identify future research opportunities. These research opportunities, as
      expressed by the conference speakers, panelists, and attendees are summarized at
      the end of this paper under five thematic areas: usage behaviors, methodology,
      pre-clinical studies and clinical studies, informational databases, and education
      and dissemination.

PMID- 15141433
TI  - The reverse tetracycline-controlled transactivator rtTA2s-S2 is toxic in mouse
      embryonic stem cells.
AB  - The efficient and reversible control of transgene expression is a powerful tool
      for the correct manipulation of embryonic stem cells in both cell therapy and
      transgenesis. The aim of this work was to investigate the possibilities of
      recently developed reverse tetracycline-controlled transactivator rtTA2s-S2. We
      show that the rtTA2s-S2 is useful for transient inducible expression of genes in
      embryonic stem cells. However, we found that it was not possible to establish
      mouse embryonic stem cell lines stably expressing this transactivator. Using the
      viral IRES sequence which couples the expression of rtTA2s-S2 and neomycin
      phosphotransferase, we found that embryonic stem cells expressing rtTA2s-S2 are
      not capable of growing in the presence of G418. Our results indicate that this
      transactivator is toxic to ES cells and raise the need for the development of
      other strategies for stable and inducible expression of genes in ES cells.

PMID- 15141434
TI  - Macromolecular source as dependent on osmotic pressure and water source: effects
      on bovine in vitro embryo development and quality.
AB  - This study evaluated the protective effect of protein, as dependent on
      osmolarity, and the quality of water sources used to prepare embryo culture
      media. In Experiment 1, two concentrations of NaCl were used to obtain culture
      media with normal (280 mOSM) and low (245 mOSM) osmolarity, each supplemented
      with either bovine serum albumin (BSA) or polyvinyl alcohol (PVA). Low osmolarity
      improved blastocyst rates in the presence of BSA (P < 0.01) and tended to do it
      in medium containing PVA (P < 0.07). Furthermore, low osmolarity allowed PVA to
      increase inner cell mass (ICM) numbers and ICM/total cell rate (P < 0.05), while
      trophectoderm (TE) and total cell counts tended to decrease (P < 0.08). In
      Experiment 2, culture media were prepared with two water sources (Milli-Q and
      Sigma-W3500-) in combination with BSA or PVA. Both water sources yielded similar
      embryo development rates, but in the presence of BSA, Milli-Q water produced
      embryos with increased ICM/total cells rates (P < 0.05). On the contrary, Sigma
      water tended to increase trophectoderm cell counts (P < 0.08). In conclusion, the
      present study showed that low osmolarity is beneficial to embryo development and
      combinations of macromolecule and osmolarity influence trophectoderm
      differentiation. Both Milli-Q and Sigma supported embryo development at
      comparable rates, although in the presence of BSA, blastocysts obtained in the
      medium prepared with Milli-Q water had superior quality in terms of ICM/total
      cells rates.

PMID- 15141435
TI  - Chorionic expression of heterogeneous products of the PAG (Pregnancy-Associated
      Glycoprotein) gene family secreted in vitro throughout embryonic and foetal
      development in the pig.
AB  - Porcine PAG (pPAG) are placental products of a multigene family that is strongly
      expressed in the chorionic epithelium (trophoblast and trophectoderm). The
      objective of this study was to define a pattern of the pPAG proteins, secreted in
      vitro by chorionic explants harvested on 16-77 days of pregnancy. Trophoblastic
      and trophectodermal explants were collected from pregnant (PR) gilts (n = 27) and
      used for protein in vitro production (8-261 h). Endometrial explants of luteal
      phase gilts (E10, n = 4) and pseudopregnant gilts (PsE, n = 2) were used as
      negative controls for protein immunoblotting. Proteins (PR, E10, PsE) were
      isolated mainly from incubation media, fractionated, dialysed and separated by
      SDS-PAGE. Heterogeneous Western blotting with various polyclonal anti-PAG sera
      raised against bovine or ovine antigens (anti-bPAG, or anti-oPAG) initially
      identified the pPAG proteins. Such blotting of fractionated chorionic proteins
      allowed for the isolation of porcine antigens that were employed as immunogens to
      raise several homologous antisera (anti-pPAG). Crude antisera were adsorbed on
      endometrial extracts or proteins of non-PR pigs, to remove non-relevant
      antibodies. The patterns of pPAG proteins secreted in vitro varied throughout
      pregnancy (35-72 kDa). During implantation, approximately 43 kDa (Day 16) or
      approximately 68.1 kDa (Days 17-25) pPAG proteins were detected. During
      placentation and as pregnancy advanced (Days 31-77), approximately 72.3 kDa pPAG
      proteins were observed. The secretions of parallel multiple smaller proteins
      (35.4-47.2 kDa), presumably, as forms of processed pPAG precursors, increased
      with the progress of gestation. In conclusion, the pPAG protein family plays a
      very important role during implantation, placenta formation and embryonic/foetal
      development in the pig.

PMID- 15141436
TI  - Opposite regulation of clusterin and LH receptor in the swine corpus luteum
      during luteolysis.
AB  - Luteolysis, which occurs in a cyclical way to remove luteal tissue, may be an
      example of physiological apoptosis which counterbalances rapid tissue growth
      after ovulation. Clusterin is a multifunctional glycoprotein expressed in
      different tissues undergoing apoptosis. In this study we investigated clusterin
      and LH receptor gene expression during luteolysis as potential regulators of
      tissue growth and regression. Luteolysis was induced in pregnant sows (45 days)
      by Cloprostenol (PGF2 alpha analogue) treatment. Clusterin expression increased
      in the corpora lutea of pregnant sows ovariectomized 0, 6, 12, 24, 48 or 72 (n =
      3) h after the luteolytic stimulus; maximum values were observed 24-48 h after
      the treatment (P < 0.01). An opposite trend between clusterin mRNA expression and
      markers of luteal function, such as progesterone levels in the corpora lutea and
      plasma, and LHr mRNA expression levels, was observed; moreover, clusterin
      expression was positively correlated with the degree of genomic DNA
      fragmentation, a marker of occurring apoptosis (P < 0.01). This pattern may be
      important in regulating luteolysis by a switch between luteotrophic and apoptotic
      stimulus. Our data indicate that P4 levels decrease prior to the increase in
      clusterin mRNA and the drop in LHr mRNA expression; we may therefore hypothesize
      a split between functional and structural luteolysis as reported in other
      species.

PMID- 15141437
TI  - Location of myostatin expression during bovine myogenesis in vivo and in vitro.
AB  - Mutations in the myostatin gene lead to double-muscling in cattle indicating that
      it is a negative regulator of the total number of muscle fibres. Myostatin
      expression was analysed by RT-PCR in three developing bovine muscles. It
      decreased during differentiation in Semitendinosus and Biceps femoris, and
      increased in the late differentiating Masseter during gestation. A combination of
      in situ hybridisation and immuno-histochemical detection of myosin heavy chains
      (MHC) allowed us to locate the expression in myofibres containing only
      developmental MHC at different stages and in fast IIA fibres at the end of
      gestation. In vitro, myostatin was undetectable during proliferation, peaked at
      the onset of fusion and decreased during terminal differentiation. It was not
      detected in myotubes by in situ hybridisation. The inhibition of differentiation
      by BrdU prevented the decrease in expression. Our results show that the peak in
      myostatin expression coincides with early differentiation indicating a regulatory
      role in cattle myogenesis.

PMID- 15141438
TI  - Insemination factors affecting the conception rate in seasonal calving Holstein
      Friesian cows.
AB  - Differences in conception rate to first service between artificial inseminations
      (AI) carried out by commercial AI operators (CAI) or do-it-yourself operators
      (DIY), between natural service (NAT) and AI, between different AI sires, and
      between fresh and frozen-thawed semen, on Irish commercial dairy farms, were
      studied using logistic regression. The study comprised 12,933 potential first
      inseminations from 77 spring-calving dairy herds. The data were recorded during
      1999 and 2000. Amongst the total, 4,394 cows had repeated records across the two
      years. Adjustment variables included: herd, year, parity, calving period, calving
      to service interval, herd size, proportion of North American Holstein-Friesian
      genes, peak milk yield, semen fresh or frozen-thawed status, AI sire and a cow
      history variable to account for the correlation structure that may exist between
      performance records of cows present in both years of the study. Interactions of
      interest were tested but were non-significant. No significant association was
      observed between the category of AI operator and the likelihood of conception
      rate to first service (PREG1). The variation in PREG1 observed within the
      category of operator (CAI and DIY) was investigated using the Levene test for
      homogeneity of variance. There was no difference between the level of variation
      observed within CAI and DIY operators. There were significant differences in the
      likelihood of PREG1 between different AI sires. Amongst the 40 most commonly used
      AI sires, 3 sires had a lower likelihood of PREG1 (P < 0.05) when compared to the
      reference AI sire (sire with PREG1 similar to the mean of the group). There was a
      tendency for a reduced likelihood of PREG1 with the use of fresh semen compared
      to frozen-thawed semen (OR = 0.80, P = 0.067). Amongst the adjustment variables
      in the model, those significantly associated with the likelihood of PREG1
      included the herd, calving period, calving to first service interval and peak
      milk yield. No significant difference in the likelihood of PREG1 was observed
      between AI and NAT.

PMID- 15141439
TI  - Influence of rumen protein degradability on productive and reproductive
      performance in buffalo cows.
AB  - The present study aimed to ascertain the influence of crude protein (CP)
      digestibility in the rumen on the quantity and quality of milk production and
      reproductive performance, blood (BU) and milk (MU) urea, haematological profile
      and vaginal mucus urea, ammonia and potassium of buffalo cows. Lactating
      buffaloes (n = 84), 60 days in milk, were randomly subdivided into Group C
      (control, n = 42) and Group T (fed a diet supplemented with Aspergillus oryzae, n
      = 42). In three fistulated buffalo, the diet supplemented with Aspergillus oryzae
      showed a decrease (P < 0.01) in protein digestibility in the rumen (79.3 vs.
      45.9%). No differences were registered in productive performance. Nine buffaloes
      not in oestrus during the dietary treatment (Groups T1 and C1), 30 days in milk,
      were used to study the haematological profile and to determine milk urea and
      ammonia in the vaginal mucus. The animals in Group T1 had higher ammonia values
      in the blood (P < 0.01) but not in the vaginal mucus than Group C1. A
      relationship was found between MU and BU. MU was influenced by CP intake and dry
      matter intake. No differences between the treatments were observed in
      reproductive performance and the conception rate and calving interval were 37.9%
      and 41.4% (90 trial-day) and 449 and 419 days respectively in Groups T and C.
      Reproductive performance was not influenced by high levels of BU nor by blood
      ammonia levels, although the latter were higher in the group fed the diet
      supplemented with Aspergillus oryzae.

PMID- 15141440
TI  - Metabolic effects of dietary lactose in adult female rats.
AB  - As an outgrowth of our interest in the potential toxicity of dietary galactose,
      we investigated the metabolic effects of high lactose diets in Long-Evans female
      rats. Seventy-five Long-Evans female rats (25-day-old) were randomized to receive
      one of 3 diets for 7 months: glucose diet (CON); low lactose diet (10.5%, LLD);
      or a high lactose diet (41.9%, HLD). Necropsy was performed seven months after
      randomization. HLD animals had significantly lower body weights than controls (P
      < 0.01). These animals continued to grow, however at a retarded rate compared to
      the CON group. The HLD group also had significantly lower triglyceride and non
      esterified fatty acid levels than the CON group (P < 0.01 and P < 0.05). Serum
      glucose concentrations were lower in the HLD group compared to CON animals (P <
      0.05), while serum insulin levels were lower than both the LLD and CON animals (P
      < 0.01 and P < 0.05). Leptin exhibited a similar trend. Thyroid studies revealed
      no difference in TSH between groups. Free T4 was significantly higher in HLD rats
      compared to LLD and CON rats while free T3 was lower in the HLD group (P < 0.05).
      This indicates a possible impairment in T4 to T3 conversion. Our data suggests
      that a long-term high lactose diet is associated with a decrease in insulin and
      leptin levels, and an increase in the insulin to glucose ratio. However, these
      changes are seen in the presence of a decreased body mass. A significant effect
      on thyroid hormone metabolism is also seen, and may be an adaptive mechanism in
      lactose-fed rats.

PMID- 15141441
TI  - Evaluation of false transrectal ultrasonographic pregnancy diagnoses in sheep by
      measuring the plasma level of pregnancy-associated glycoproteins.
AB  - The present study was undertaken to investigate to what extent pregnancy
      diagnoses made by transrectal ultrasonography could be confirmed by measurements
      of plasma concentration of ovine pregnancy-associated glycoproteins (ovPAG). A
      total of 424 Awassi x Merino ewes were synchronized for estrus and examined by
      transrectal ultrasonography. In Experiment 1, the ewes (n = 156) were repeatedly
      scanned in a standing position on d 29, 36 and 50 of gestation. Similarly, the
      ewes (n = 268) in Experiment 2 were scanned on d 24, 29 and 34 of gestation, but
      these ewes were fasted for 12 h prior to the examination and the abdominal wall
      of each animal was lifted up by the hands of the assistant during the scanning.
      Blood samples were withdrawn after each transrectal ultrasonographic examination
      in both experiments. Ovine PAG concentrations were measured in plasma by a
      heterologous radioimmunoassay and the cut-off value for pregnancy was > or = 1
      ng.mL-1. Based on the lambing performance, in Experiment 1, altogether 47 false
      negative and 38 false positive diagnoses were made by transrectal ultrasonography
      in 24 and 33 ewes, respectively between d 29 and 50 of gestation. In Experiment
      2, altogether 8 false negative and 13 false positive diagnoses both were made in
      7 ewes between d 24 and 34 of gestation. In both experiments, all ewes with false
      negative diagnoses had ovPAG concentrations higher than the threshold level for
      pregnancy diagnosis and all ewes with false positive diagnoses had ovPAG
      concentrations lower than the threshold of pregnancy. Furthermore, by the PAG-RIA
      test all lambed or aborted ewes (n = 63) were correctly diagnosed as pregnant and
      with three exceptions, all non-lambed ewes (n = 361) were correctly diagnosed as
      non-pregnant during the examined periods of both experiments.

PMID- 15141442
TI  - Using science to assess environmental vulnerabilities.
AB  - Beginning in 1995, the U.S. Environmental Protection Agency (U.S. EPA), Office of
      Research and Development has focused much of its ecological research in the Mid
      Atlantic as part of the Mid-Atlantic Integrated Assessment (MAIA). The goal of
      MAIA is to improve the assessability of scientific information in environmental
      decision-making. Following the Environmental Monitoring and Assessment Program
      (EMAP) whose goal is to guide monitoring that effectively reflects current
      ecosystem condition and trends, MAIA's second, current, phase of research under
      the Regional Vulnerability Assessment (ReVA) program is designed to target risk
      management activities using available data and models. The papers presented here
      are from a conference held in May 2003 that presented results of research in this
      second phase of MAIA. The conference was organized into the following topics: 1.
      Assessing Current Impacts and Vulnerabilities 2. Forecasting Environmental
      Condition and Vulnerabilities 3. Developing Management Strategies to Optimize the
      Future, and 4. Assessing and Responding to Environmental Vulnerability.

PMID- 15141443
TI  - Assessing wetland condition on a watershed basis in the Mid-Atlantic region using
      synoptic land-cover maps.
AB  - We developed a series of tools to address three integrated tasks needed to
      effectively manage wetlands on a watershed basis: inventory, assessment, and
      restoration. Depending on the objectives of an assessment, availability of
      resources, and degree of confidence required in the results, there are three
      levels of effort available to address these three tasks. This paper describes the
      development and use of synoptic land-cover maps (Level 1) to assess wetland
      condition for a watershed. The other two levels are a rapid assessment using
      ground reconnaissance (Level 2) and intensive field assessment (Level 3). To
      illustrate the application of this method, seven watersheds in Pennsylvania were
      investigated representing a range of areas (89-777 km2), land uses, and
      ecoregions found in the Mid-Atlantic Region. Level 1 disturbance scores were
      based on land cover in 1-km radius circles centered on randomly-selected wetlands
      in each watershed. On a standardized, 100-point, human-disturbance scale, with
      100 being severely degraded and 1 being the most ecologically intact, the range
      of scores for the seven watersheds was a relatively pristine score of 4 to a
      moderately degraded score of 66. This entire process can be conducted in a
      geographic information system (GIS)-capable office with readily available data
      and without engaging in extensive field investigations. We recommend that
      agencies and organizations begin the process of assessing wetlands by adopting
      this approach as a first step toward determining the condition of wetlands on a
      watershed basis.

PMID- 15141444
TI  - Using spatial interpolation to estimate stressor levels in unsampled streams.
AB  - Accurate estimates of stressor levels in unsampled streams would provide valuable
      information for managing these resources over large regions. Spatial
      interpolation of stream characteristics have rarely been attempted, partly
      because defining separation distances between distinct stream samples is not
      straightforward. That is, conventional Eulerian definitions of separation
      distance may not apply to stream networks where information flows along distinct
      paths. A two-stage model for estimating stressor levels in unsampled streams is
      presented. Mean characteristics within streams are predicted usign a generalized
      additive model and residual variation is estimated using a conventional
      application of spatial statistics. The model is developed and tested using stream
      survey data collected in the state of Maryland, USA. Model efficiency is compared
      for three stream variables (nitrate concentration, sulfate concentration, and
      epifaunal substrate score) known to be associated with biological impairments in
      streams. Accounting for spatial autocorrelation in the residual variation
      improved model R2 from 0.71 to 0.81 for nitrate, from 0.29 to 0.63 for sulfate,
      and from 0.21 to 0.31 for epifaunal substrate score.

PMID- 15141445
TI  - Landscape ecological assessment of the Chesapeake Bay watershed.
AB  - The Chesapeake Bay Watershed, located in the Mid-Atlantic Region of the United
      States, is experiencing rapid habitat loss and fragmentation from sprawling low
      density development. The bay itself is heavily stressed by excess sediment and
      nutrient runoff. Three states, the District of Columbia, and the federal
      government signed an agreement in 2000 to address these problems. The commitments
      included an assessment of the watershed's resource lands, and targeting the most
      valued lands for protection. As part of this task, the Resource Lands Assessment
      identified an ecological network comprised of large contiguous blocks (hubs) of
      forests, wetlands, and streams, interconnected by corridors to allow animal and
      plant propagule dispersal and migration. Hubs were prioritized by ecoregion, by
      analyzing a variety of ecological parameters, including: rare species presence,
      rarity and population viability; vegetation and vertebrate richness; habitat
      area, condition, and diversity; intactness and remoteness; connectivity
      potential; and the nature of the surrounding landscape. I found that much of the
      watershed was still fairly intact, although this varied dramatically by
      ecoregion. Current protection also varied, and an assessment of vulnerability
      will help focus protection efforts among the most valuable hubs and corridors.

PMID- 15141446
TI  - Migration of birds as an indicator of broad-scale environmental condition.
AB  - The migration of Neotropical birds may provide a robust measure of changing
      environmental condition along the migratory route. I review previous work on
      assessing broad-scale stopover quality in the eastern United States and discuss
      how future research can aid regional environmental assessment. Scientists can
      quantify how environmental changes affect the migratory system, and then monitor
      for those effects on migrant abundance from year to year. The cyclical nature of
      migration provides a constant re-evaluation of habitat quality and spatial
      distribution by migrant birds. Avian monitoring programs can detect changes in
      migrant abundance. Migrating birds may thus provide a living sensor of
      environmental change, enabling broad-scale environmental assessments to detect
      and address habitat degradation early on, allowing local managers to prioritize
      restoration efforts accordingly. Understanding the environmental factors driving
      stopover selection, and how birds move between stopovers during migration, is an
      important first step.

PMID- 15141447
TI  - Evaluating quality of life, economic vulnerabilities, and drivers of ecosystem
      change.
AB  - We examined regional conditions and trends related to quality of life and
      potential vulnerabilities of these factors to changes in the condition of natural
      resources in the Mid-Atlantic Region, USA. We selected a variety of variables on
      economic and socio-demographic conditions that demonstrate links between the
      condition of natural areas and human concerns and that quantify dependencies on
      resources. We extracted data from economic and population census databases for
      counties within the study area and present a subset of results of the cluster
      analyses used to describe condition and potential risks due to distinct
      combinations of variables. We found that the same variables used to judge quality
      of life were often correlated with increasing population and thus were likely to
      be related to land pressures and risks to natural resources. Within the region,
      economic dependence on resource-harvesting industries such as forestry and
      fisheries was low (less than 4% of total earnings at most), however, the
      potential for natural amenities to attract residents appeared to be growing as
      the self-employed and otherwise mobile people settled in areas with affordable
      housing and natural amenities. Suburban residential spread had been occurring in
      both the close-in and distant suburbs of the region's urban areas and some rural,
      growth appeared to be driven, in part, by businesses migrating to suburbs.
      Further work is needed to tease apart causal factors for the trends we observed,
      but correlations clearly existed in some areas between increasing populations and
      quality of natural surroundings.

PMID- 15141448
TI  - Evaluating habitat as a surrogate for population viability using a spatially
      explicit population model.
AB  - Because data for conservation planning are always limited, surrogates are often
      substituted for intractable measurements such as species richness or population
      viability. We examined the ability of habitat quality to act as a surrogate for
      population performance for both Red-shouldered Hawks (Buteo lineatus) and
      Northern Goshawks (Accipiter gentilis). We compared simple measures of habitat
      quality to estimates of population growth rates obtained from a spatially
      explicit model of population dynamics. We found that habitat quality was a
      relatively poor predictor of simulated population growth rates for several
      reasons. First, a relatively small proportion of the potential habitat for each
      species served as population sources in our simulations--15% for Red-shouldered
      Hawks and 2% for Goshawks. Second, when habitat quality correctly predicted
      demographic sources on the landscape, it consistently underestimated the
      contribution of these areas to the population. In areas where habitat quality
      correctly anticipated the presence of demographic sinks, we found no useful
      quantitative relationship between the two measures. Our simulation model captured
      the influence of habitat quality on the hawk populations, but it also
      incorporated interactions between dispersing individuals and landscape patterns.
      Thus, the discrepancies we observed likely reflected the influence of forest
      fragmentation and the spatial arrangement of forest patches on the populations.
      We conclude that simple measures of habitat quality will often be poor surrogates
      for population persistence, but that spatially explicit population models can
      help inform the development of better indices.

PMID- 15141449
TI  - Vulnerability of Mid-Atlantic forested watersheds to timber harvest disturbance.
AB  - Forested watersheds of the Mid-Atlantic Region are an important economic
      resource. They are also critical for maintaining water quality, sustaining
      important ecological services, and providing habitat to many animal and plant
      species of conservation concern. These forests are vulnerable to disturbance and
      fragmentation from changing patterns of land use in the Mid-Atlantic Region, and
      from harvests of commercially mature and relatively inexpensive timber. The U.S.
      Department of Agriculture Forest Service (USDA-FS) Forest Inventory and Analysis
      (FIA) compiles data on forest condition by state and county. We have transformed
      these FIA data to a U.S. Geological Survey (USGS) 6-digithdrologic unit code (HUC
      6) watershed base, and projected trends in timber growth, inventory, and harvest
      to 2025 using a timber economics forecasting model (SRTS). We consider forest
      sustainability from the perspective of timber production, and from the
      perspective of landscape stability important to conservation values. Simulation
      data is combined with FIA planted pine acreage data to form a more complete
      picture of forest extent, composition, and silvicultural practice. Early
      recognition of prevailing economic trends which encourage the fragmentation of
      mature forests due to increasing timber harvests may provide managers and policy
      makers with a planning tool to mitigate undesirable impacts.

PMID- 15141450
TI  - Scenario analysis for the San Pedro River, analyzing hydrological consequences of
      a future environment.
AB  - Studies of future management and policy options based on different assumptions
      provide a mechanism to examine possible outcomes and especially their likely
      benefits and consequences. The San Pedro River in Arizona and Sonora, Mexico is
      an area that has undergone rapid changes in land use and cover, and subsequently
      is facing keen environmental crises related to water resources. It is the
      location of a number of studies that have dealt with change analysis, watershed
      condition, and most recently, alternative futures analysis. The previous work has
      dealt primarily with resources of habitat, visual quality, and groundwater
      related to urban development patterns and preferences. In the present study,
      previously defined future scenarios, in the form of land-use/land-cover grids,
      were examined relative to their impact on surface-water conditions (e.g., surface
      runoff and sediment yield). These hydrological outputs were estimated for the
      baseline year of 2000 and predicted twenty years in the future as a demonstration
      of how new geographic information system-based hydrologic modeling tools can be
      used to evaluate the spatial impacts of urban growth patterns on surface-water
      hydrology.

PMID- 15141451
TI  - Assessing development pressure in the Chesapeake Bay watershed: an evaluation of
      two land-use change models.
AB  - Natural resource lands in the Chesapeake Bay watershed are increasingly
      susceptible to conversion into developed land uses, particularly as the demand
      for residential development grows. We assessed development pressure in the
      Baltimore-Washington, DC region, one of the major urban and suburban centers in
      the watershed. We explored the utility of two modeling approaches for forecasting
      future development trends and patterns by comparing results from a cellular
      automata model, SLEUTH (slope, land use, excluded land, urban extent,
      transportation), and a supply/demand/allocation model, the Western Futures Model.
      SLEUTH can be classified as a land-cover change model and produces projections on
      the basis of historic trends of changes in the extent and patterns of developed
      land and future land protection scenarios. The Western Futures Model derives
      forecasts from historic trends in housing units, a U.S. Census variable, and
      exogenously supplied future population projections. Each approach has strengths
      and weaknesses, and combining the two has advantages and limitations.

PMID- 15141452
TI  - Criteria to assess and select sites for long-term avian monitoring in an
      urbanizing landscape.
AB  - A methodology was developed to prioritize the suitability of sites for long-term
      monitoring of avian populations, including vulnerable species, both to enhance
      assessment of changes in ecological resources and to facilitate land-use planning
      at the regional scale. This paper argues that a successful monitoring program
      begins with a site prioritization procedure that integrates scores based on
      spatial controls with ecological and socio-economic indicators, particularly
      those dependent on community involvement. The evaluation strategy in this study
      combines 1) spatial controls such as land ownership and accessibility, with 2)
      biological and habitat indicators such as vulnerable species and habitat
      connectivity, and 3) community and agency variables such as volunteer commitment
      and agency priorities. In total, a set of ten indicators was identified. This
      strategy was applied to predominantly agricultural landscapes, which are
      experiencing increasing human pressures, in three sub-watersheds of the Credit
      River, Southern Ontario. Specifically, bird populations were recorded during the
      breeding seasons of 2000-2002 in nine land units or habitat types including
      marsh, deciduous forest, and grasslands as mapped by Credit Valley Conservation
      (CVC) following Ecological Land Classification (ELC) guidelines. CVC selected
      sites for long-term monitoring in 2002 and the relationships between the scored
      (or ranked) sites and the selected long-term monitoring sites are discussed.

PMID- 15141453
TI  - Environmental impacts of dispersed development from federal infrastructure
      projects.
AB  - Dispersed development, also referred to as urban growth or sprawl, is a pattern
      of low-density development spread over previously rural landscapes. Such growth
      can result in adverse impacts to air quality, water quality, human health,
      aquatic and terrestrial ecosystems, agricultural land, military training areas,
      water supply and wastewater treatment, recreational resources, viewscapes, and
      cultural resources. The U.S. Environmental Protection Agency (U.S. EPA) is
      charged with protecting public health and the environment, which includes
      consideration of impacts from dispersed development. Specifically, because
      federal infrastructure projects can affect the progress of dispersed development,
      the secondary impacts resulting from it must be assessed in documents prepared
      under the National Environmental Policy Act (NEPA). The Council on Environmental
      Quality (CEQ) has oversight for NEPA and Section 309 of the Clean Air Act
      requires that U.S. EPA review and comment on federal agency NEPA documents. The
      adverse effects of dispersed development can be induced by federal infrastructure
      projects including transportation, built infrastructure, modifications in natural
      infrastructure, public land conversion and redevelopment of properties,
      construction of federal facilities, and large traffic or major growth generation
      developments requiring federal permits. This paper presents an approach that U.S.
      EPA reviewers and NEPA practitioners can use to provide accurate, realistic, and
      consistent analysis of secondary impacts of dispersed development resulting from
      federal infrastructure projects. It also presents 24 measures that can be used to
      mitigate adverse impacts from dispersed development by modifying project location
      and design, participating in preservation or restoration activities, or informing
      and supporting local communities in planning.

PMID- 15141454
TI  - Sustainability indicators as a communicative tool: building bridges in
      Pennsylvania.
AB  - Sustainability is a laudable goal, but difficult to define and to implement
      because of the complexity of interlinked human and natural systems, and the
      uncertainty inherent in such complex systems. Resilience shows promise as a
      relevant and measurable attribute of sustainability, which itself defies
      measurement. Identification and assessment of conditions that are desirable, as
      well as those that are undesirable, are necessary in order to determine both the
      degree of progress toward sustainability and the removal of impediments to such
      progress. Communications incident to the identification and selection of
      indicators of resilience and sustainability are of potentially greater value than
      the indicators themselves and so should be given explicit consideration in the
      design of the indicators development process. Moving towards sustainability
      requires an iterative, continuing (open-ended), collaborative process. Academic
      institutions can assist in this process through activities that connect across
      political, social and discipline boundaries. Boundary organizations are those
      that have achieved a level of trust among the relevant constituents to management
      of sustainability and can help convert academic findings that are objectively
      neutral into options and alternatives that may be politically and economically
      feasible. The Sustainable Pennsylvania Program is developing demonstration
      projects with both state and local governmental agencies with the objective of
      building both capacity and will for moving towards sustainability.

PMID- 15141455
TI  - The public policy aspects of biological monitoring: budget and land-use planning
      implications at the county level.
AB  - Montgomery County, Maryland faces a growing problem that confronts local
      governments across the country: the cumulative impacts that population growth and
      the resulting land-use changes are having on local streams and their accompanying
      ecosystems. County officials found they needed an affordable tool to serve as a
      report card for stream health, and began a biomonitoring program in 1994. By 1997
      county officials had monitored all 23 watersheds within the county's boundaries,
      and in 1998 the county published its first Countywide Stream Protection Strategy
      (CSPS). The County uses the CSPS to prioritize its watershed restoration efforts
      to those areas most in need of immediate remediation. Six primary programs now
      support or require the use of information from Montgomery County's biomonitoring
      program. And, the lessons learned from Montgomery County can help other county
      and local governments develop similar programs of their own.

PMID- 15141456
TI  - Innovative environmental education contributes to improved management practices
      in the Mid-Atlantic region of the United States.
AB  - The Mid-Atlantic Integrated Assessment (MAIA) and its partner, University of
      Maryland, Baltimore County (UMBC) have developed a graduate-level course focused
      on successful application of science by decision-makers to address a particular
      problem. Students conduct a literature review, interview the decision-makers and
      scientists, and synthesize and document the management problem, the science that
      was applied to that problem, and other issues that might constrain or drive the
      solution (e.g., legalities, social pressures, expense, politics, personalities,
      etc.). Students also quantify the results, evaluate who the intended audience is
      and how they most appropriately target them, and determine if there are other
      management problems that could be addressed with the science. The final products
      are short publications geared towards other decision-makers who might have a
      similar problem and might be seeking successful innovative solutions. MAIA is
      distributing these short publications to decision-makers throughout the Mid
      Atlantic Region. The publications have been very positively received by state and
      local governments and watershed groups.

PMID- 15141457
TI  - Keeping the books for environmental systems: an emergy analysis of West Virginia.
AB  - Emergy provides a general accounting mechanism that allows us to view the economy
      and the environment on the same income statement and balance sheet. This allows
      an auditor to verify the economic picture by checking it against a more complete
      representation of the flows and storages of real wealth as measured by emergy. In
      this study, we constructed emergy accounts for the state of West Virginia in
      1997. The income statement showed annual production, consumption, and flows of
      emergy and dollars into and out of the state. The balance sheet evaluated the
      storage of emergy in some of the state's assets. Emergy indices were used to
      answer questions posed by managers and gain insight into the state's economic and
      environmental strengths and weaknesses. West Virginia has great wealth in
      nonrenewable resources (9E14 sej m-2 or 17 times the U.S. average). The
      investment ratio of emergy purchased outside to indigenous renewable and
      nonrenewable emergy was 2.2:1, which indicates a high potential for future
      development. However, the environmental loading ratio (14:1) was already 1.5
      times higher than that found at an average location in the U.S. Twice as much
      emergy was exported as received and standard of living indicators showed that
      people have largely failed to benefit from their state's wealth. We propose that,
      just as in business, where decisions made using financial accounts ensure
      solvency; decisions governing the environment should be made based on an emergy
      accounting of activities, assets, and liabilities for the combined system of
      humanity and nature.

PMID- 15141458
TI  - A regional approach to projecting land-use change and resulting ecological
      vulnerability.
AB  - This study explores ecological vulnerability to land-use change in the U.S. Mid
      Atlantic Region by spatially extrapolating land and economic development, and
      overlaying these projections with maps of sensitive ecological resources. As
      individual extrapolations have a high degree of uncertainty, five methods with
      different theoretical bases are employed. Confidence in projections is increased
      for counties targeted by two or more projection methods. A county is considered
      at risk if it currently supports three or more sensitive resources, and is
      projected to experience significant growth by the year 2010 by two or more
      methods. Analysis designated 19 counties and two cities as at risk, highlighting
      within a large region the priority areas where state and regional efforts would
      contribute the most to integrating environmental considerations into the process
      of land development. The study also found that potentially severe ecological
      effects of future land-use change are not limited to the outskirts of major urban
      areas. Recreational demands on smaller communities with mountain and coastal
      resources are also significant, as are initiatives to promote economic
      development in rural areas of high ecological quality. This approach provides a
      comprehensive overview of potential regional development, leading to an objective
      prioritization of high-risk areas. The intent is to inform local planning and
      decision-making so that regional and cumulative ecological degradation are
      minimized.

PMID- 15141459
TI  - An overview of data integration methods for regional assessment.
AB  - The U.S. Environmental Protections Agency's (U.S. EPA) Regional Vulnerability
      Assessment(ReVA) program has focused much of its research over the last five
      years on developing and evaluating integration methods for spatial data. An
      initial strategic priority was to use existing data from monitoring programs,
      model results, and other spatial data. Because most of these data were not
      collected with an intention of integrating into a regional assessment of
      conditions and vulnerabilities, issues exist that may preclude the use of some
      methods or require some sort of data preparation. Additionally, to support multi
      criteria decision-making, methods need to be able to address a series of
      assessment questions that provide insights into where environmental risks are a
      priority. This paper provides an overview of twelve spatial integration methods
      that can be applied towards regional assessment, along with preliminary results
      as to how sensitive each method is to data issues that will likely be encountered
      with the use of existing data.

PMID- 15141460
TI  - Integrated environmental assessment of the Mid-Atlantic region with analytical
      network process.
AB  - A decision analysis method for integrating environmental indicators was
      developed. This was a combination of Principal Component Analysis (PCA) and the
      Analytic Network Process (ANP). Being able to take into account the
      interdependency among variables, the method was capable of ranking ecosystems in
      terms of environmental conditions and suggesting cumulative impacts across a
      large region. Using data on land cover, population, roads, streams, air
      pollution, and topography of the Mid-Atlantic Region of the United States, we
      were able to point out areas which were in relatively poor condition and/or
      vulnerable to future deterioration regarding various environmental aspects. The
      method offered an easy and comprehensive way to combine the strengths of
      conventional multivariate statistics (PCA) and decision-making science tool (ANP)
      for integrated environmental assessment.

PMID- 15141461
TI  - Improving the analytical performances of inductively coupled plasma optical
      emission spectrometry by multivariate analysis techniques.
AB  - The various multivariate analysis techniques which have been successfully applied
      to maximize the analytical performance of ICP-OES are reviewed. These include
      optimization procedures, spectral data processing and calibration methods as well
      as classification and pattern recognition techniques.

PMID- 15141462
TI  - Polycyclic aromatic hydrocarbons in the atmosphere: monitoring, sources, sinks
      and fate. I: Monitoring and sources.
AB  - This is the first of a series of two papers intended to review the state-of-the
      art knowledge on atmospheric PAHs, concerning their monitoring, sources and
      transformation processes in the atmosphere. The monitoring section briefly
      introduces this class of compounds, mainly focusing on the 16 PAHs indicated by
      the US-EPA as priority pollutants. These compounds undergo partitioning between
      the gas phase and particulate, which has to be considered in the choice of the
      sampling methodology. Furthermore, sampling artifacts may arise from further
      phase transfers inside the sampling device. After sampling, extraction, clean up
      and detection/quantification procedures will follow. They are closely related
      since the choice of the extraction technique will heavily condition the clean-up
      step, and both procedures will place demands on the performance of the detection
      technique (usually GC-MS or HPLC). This is particularly true in the case of
      complex samples such as those arising from atmospheric sampling. The sources of
      atmospheric PAHs are then discussed with a particular focus on receptor models,
      which can allow the apportionment of PAH sources based on concentration data that
      can be routinely obtained by pollution control networks.

PMID- 15141463
TI  - Selective transition metal extraction by reverse micelles.
AB  - In this report we have studied the extraction of a series of heavy metals ions
      (Cu2+, Ni2+, Fe3+, Cr3+, CrO4(2-)) from water bulk solutions by means of reverse
      micelles. The parameters explored are the nature and concentration of the
      accompanying electrolyte, as well as the surfactant nature and its concentration.
      The extracted metals can be recovered and eventually concentrated in a new water
      solution carrying out a back extraction. The extracted amount of metal is
      strongly dependent on the charge of the metal to be extracted. Therefore the
      extracted water solution is enriched in higher charge metal. Anions of amphoteric
      metals, like the chromate ions, can be quantitatively separated from their
      positive cations, like Cr3+ by properly choosing the cationic or the anionic
      surfactants. The transfer of the metal is essentially controlled by electrostatic
      forces. A model based on the Poisson-Boltzmann distribution allow us to get the
      potential profile inside the water pool by determining the concentrations of the
      surfactant counter ions. From the potential profile and mass balance it is
      possible calculate the extraction percentage.

PMID- 15141464
TI  - Penicillamine disulfide (PNS) and alkaline cations.
AB  - D-penicillamine disulfide (PNS) shows protolytic properties and is able to form
      complexes with cations, because it has two aminic groups and two carboxylic
      groups. The four protonation constants of its deprotonated species were
      determined by means of electromotive force (e.m.f.) measurements of a galvanic
      cell involving a glass electrode at 25 degrees C and in a constant ionic medium
      constituted by N(CH3)4Cl 3.00 or 1.00 mol dm-3. At 25 degrees C and in 3.00 mol
      dm-3 N(CH3)4Cl as ionic medium, equilibria taking place between PNS and lithium,
      sodium and potassium ions were investigated. Experimental data, again obtained
      from e.m.f. measurements, were explained by assuming the formation of species of
      the type MH2PNS ed M2H2PNS, where M indicates a cation. Stability constants for
      each proposed species were calculated. A comparison with cystine is discussed.

PMID- 15141465
TI  - Heavy metal in sediments and bioaccumulation in the bivalve Corbula gibba in a
      drilling discharge area.
AB  - The longterm bioavailability of heavy metals in sediments of a Northern Adriatic
      Sea shelf area affected by drilling mud and cutting discharges was discussed.
      Levels of Mn, Cu, Cr, Zn and Pb in different geochemical phases of the sediment
      and in soft tissues of the bivalve Corbula gibba were recorded and the
      relationships between biological and geochemical metal investigated. Total metal
      content, acetic acid extractable-, exchangeable-, carbonate-, easily reducible-,
      moderately reducible-, oxidable- and residual-fractions were determined on
      sediment samples. Corbula gibba was collected from wet sediments at the same
      times and sites, and the soft-tissue metal contents were determined. Correlations
      show that the fractions with greatest bioavailability are the exchangeable and
      carbonate for Cr and the exchangeable, carbonate, easily and moderately reducible
      fractions for Zn. Data also show a possible bioavailability of Pb only from the
      residual fraction, consisting of very resistant matter of more recent
      anthropogenic origin. Near the platform, total Mn content in sediments and in C.
      gibba tissues show a strong correlation suggesting that this organism is
      sensitive to variations of the Mn-oxi-hydroxides superficial film. No
      relationships were found between biological and sediment-bound Cu, however the
      discharged muds did not cause Cu enrichment. The metal fraction determined by
      weak acetic acid extraction at no point seems related to metal levels in Corbula
      gibba.

PMID- 15141466
TI  - Validation of an HPLC method for the determination of fleroxacin and its photo
      degradation products in pharmaceutical forms.
AB  - HPLC determination of fleroxacin in dosage forms was carried out using either
      reversed-phase column YMC pack ODS-AQ or Supelco LC Hisep shielded hydrophobic
      phase column, with UV detection at 280 nm. The mobile phase for ODS column
      consisted of 50:50:0.5 v/v/v and for Hisep column 15:85:0.5 v/v/v acetonitrile
      water-triethylamine. The pH of the mobile phase was adjusted to 6.30 for ODS
      column and to 6.85 for Hisep column, with H3PO4. Linear response was obtained in
      the concentration range of fleroxacin between 0.01 and 1.30 micrograms/mL.
      Detection limit was 4.8 ng/mL. Recovery test in the determination of fleroxacin
      in "Quinodis" tablets (Hoffmann La Roche, nominal mass 400 or 200 mg) was 98-101%
      for both columns. The effect of the composition and pH of the mobile phase on
      spectra, retention time and dissociation constants of fleroxacin was discussed.
      The proposed method could be also used for separation of the photo-degradation
      products of fleroxacin. Ten degradation products were separated on the ODS-AQ
      column, thus confirming the suitability of the proposed method for stability
      study of fleroxacin in pharmaceuticals.

PMID- 15141467
TI  - Heavy metals and adsorbents effects on activated sludge microorganisms.
AB  - The sorption of Cu(II) and Cd(II) from synthetic solution by powdered activated
      carbon (PAC), biomass, rice husk (RH) and activated rice husk (ARH) were
      investigate under batch conditions. After activated by concentrated nitric acid
      for 15 hours at 60-65 degrees C, the adsorption capacity for RH was increased.
      The adsorbents arranged in the increasing order of adsorption capacities to the
      Langmuir Q degree parameter were biomass > PAC > ARH > RH. The addition of
      adsorbents in base mix solution had increased the specific oxygen uptake rate
      (SOUR) activated sludge microorganisms with and without the presence of metals.
      The increased of SOUR were due to the ability of PAC and RH in reducing the
      inhibitory effect of metals on microorganisms and provide a reaction site between
      activated sludge microorganisms and substrates.

PMID- 15141469
TI  - A possible proposition of work in analytical method validation.

PMID- 15141468
TI  - Evaluation of procedures for the extraction and purification of neomycin
      phosphotransferase II from a genetically modified agrobacterium.

PMID- 15141470
TI  - Determination of heavy metals in honey by Zeeman electrothermal atomic absorption
      spectrometry.

PMID- 15141471
TI  - On some structural features of ovarian ligaments in domestic animals.
AB  - The vascular and nerve components of ovarian ligaments (proper and suspensory) of
      the sheep, cow and the donkey were examined in order to investigate the presence
      of blood flow-regulator endovasal devices, artero-venous anastomoses, free and/or
      encapsulated nerve endings and ganglion cells. Both the ligaments of the
      investigated species showed the presence of endovasal devices (valvular apparati,
      intimal and polypoid cushions) and artero-venous anastomoses, the latter
      structurally ascribed to the first and second type of Conti and Bucciante's
      classification. Moreover, although not constantly, both the examined districts
      showed an autonomic nerve support, while four Ruffini's corpuscles were found in
      the suspensory ligament just in one sheep.

PMID- 15141472
TI  - The superficial ulnar artery originating from the left brachial artery.
AB  - An anomalous superficial ulnar artery was found in the left arm of a 60-year-old
      man during anatomical dissection. It originated from the brachial artery
      approximately 6 cm distally to profound brachial artery. It crossed over the
      median nerve and coursed ventral to the nerve, but inferior to the bicipital
      aponeurosis and superficial to the flexor muscles. At the palm, it formed the
      superficial and deep palmar arches together with the branches of the radial
      artery. The clinical importance of the anomalous ulnar artery is discussed.

PMID- 15141473
TI  - Morphological and morphometric characteristics of choroid plexus psammoma bodies
      during the human aging.
AB  - Psammoma bodies are one of many choroid plexus aging changes which origin is
      still enigma for the scientists. During our investigation psammoma bodies were
      studied on 30 postmortem brains by light microscopy. They stained red with HE,
      and were PAS and AB PAS positive. The largest number of lamellas were stained
      blue with Mallory's connective tissue stain, except peripheral and next to the
      center lamella which stained red. During the aging, psammoma bodies became larger
      and more irregular, which was followed with group area and perimeter, single
      psammoma body average area and average perimeter, average diameter and contour
      index increase. Psammoma bodies mearged in the second and the third age group and
      mearging process led to larger and more irregular structures formation. The
      results of this investigation suggest that psammoma bodies are more frequent in
      choroid plexus of healthy older people and during the aging they obtain larger
      dimensions, more irregular contours, which is the result of their mutual
      mearging.

PMID- 15141475
TI  - Catecholaminergic phenotype of human Leydig cells.
AB  - Catecholamines are neurotransmitters involved in the regulation of testicular
      function and they activate the Leydig cell receptors. To assess whether the two
      key-enzymes involved in the synthesis of catecholamines are present in human
      testis we examined the expression of Tirosine Hydroxylase (TH) and Dopamine-beta
      Hydroxylase (DBH) antigens by immunoperoxidase and immunofluorescence techniques.
      Sections from testicular biopsies of adult and infant patients were processed by
      two antibodies. In all specimens Leydig cells stain positively. Differences in
      the staining positivity among single Leydig cells and among cell groups as well
      as among Leydig cells from different patients were noted. In some of the
      reactions a small number of Leydig cells was negative. Most of the
      immunoreactivity is evenly distributed within the cytoplasm of the Leydig cells.
      We suggest that the heterogeneous expression among Leydig cells could be
      correlated to their different metabolic activity. Our observations show a local
      intratesticular source of catecholamines which, in concert with nervous and blood
      stream sources, could be involved in the spermatogenesis regulation. In
      particular, during psychogenic or somatic stress situations also the local
      catecholamine production by autocrine and/or paracrine mechanism could contribute
      to the high concentration of catecholamines and to suppression of the testicular
      functions.

PMID- 15141474
TI  - Structure and ultrastructure of microvessels in the kidney seen by the corrosion
      casting method.
AB  - Scanning electron microscopic observation of corrosion casts is the finest
      technique to describe spatial patterns of microvessels in many organs, giving a
      readily interpreted representation of their vascular architecture without
      interference from surrounding tissues. We focused on the renal cortex of guinea
      pigs to make an in-depth morphological analysis of structural and ultrastructural
      details left by the cells on the resin cast. In addition, we made a qualitative
      description of normal variants usually observed in glomerular disposition,
      arteriolar morphology or capillary arrangement in the space to shed more light on
      the relationship between vascular tissue and surrounding cells. The study also
      disclosed some examples of vascular adaption to physiological and pathological
      conditions occurring in renal microvessels such as many systems essential to flow
      regulation, filtration and excretory processes. At lower magnification, all major
      vessels can be readily distinguished: interlobar, arciform and interlobular
      arteries and veins, along with a web of peritubular and capsular capillaries. At
      higher magnification, the glomeruli become visible and the afferent and efferent
      arteries and the tortuosity the inner vessels can be distinguished. In some of
      them, the resin, due to the narrowing sizes, suddenly stopped leaving a half
      casted glomerulus. This helped to reveal its internal circulation characterized
      by thin capillaries with a high degree of bi or trifurcation. In addition, we
      confirmed the close correspondence between cellular ultrastructural detail
      (pores, corrugations of cellular membrane, perivascular cell branches) and the
      impressions left on the resin visible only at high magnifications.

PMID- 15141476
TI  - Expression of protein kinase C (PKC) alpha, delta, epsilon, zeta in primary chick
      chondrocyte cultures: immunocytochemical study.
AB  - PKC is a family of 12 serine/threonine isoenzymes that plays a pivotal role in
      signal transduction in a large number of biological processes. In the present
      work we have investigated the expression of PKC (alpha, delta, epsilon, zeta) in
      chick chondrocyte primary cultures at different differentiation times, i.e. at
      48, 55, 62 and 69 days after cell collection from tibiae of 6-day old chick
      embryos. We would also detect cell differentiation stages towards the osteoblast
      like cell phenotype by observing the immunocytochemical expression of the
      specific osteoblast marker, type I collagen. At the considered culture times,
      cells exhibited immunocytochemical positivity for type I collagen, thus showing
      their differentiation towards the osteoblast-like phenotype. PKC-zeta was the
      isoenzyme that exhibited the most relevant immunocytochemical expression in all
      considered culture times, whereas PKC-epsilon always less expressed in comparison
      to the other PKC-isoforms. No relevant differences were observed for the
      immunocytochemical expressions of PKC-alpha and PKC-delta. On the basis of the
      immunocytochemical data obtained from the present investigation, we could affirm
      that PKC-alpha, -delta, -epsilon, and -zeta may play peculiar roles in the
      differentiation process of chick chondrocytes towards the osteoblast-like cell
      phenotype.

PMID- 15141477
TI  - Introducing secondary school students to biotechnology: the project "Biotech a
      Scuola".

PMID- 15141478
TI  - SIBMA 2003: annual meeting of the Marine and Environmental Biochemistry Group.

PMID- 15141479
TI  - Methylation profile of P. lividus sea urchin genes during development.
AB  - Methylation pattern has been studied in two genes of sea urchin Paracentrotus
      lividus using sodium bisulfite method to understand the possible role of DNA
      methylation during invertebrate development. Three regions of the gene for the
      hatching enzyme have been analyzed and all of them resulted unmethylated in
      embryos at different stages of development. Four CpG rich regions have been
      studied in the gene for DNA methyltransferase: upstream, upstream-exon1, intron 1
      and exon 20. The upstream-exon 1 region is always unmethylated, while intron 1
      and exon 20 are heavy methylated. Only the upstream fragment changed its pattern
      of methylation during development. For none of the studied regions the reported
      data show a general direct correlation between gene expression and methylation
      process during development.

PMID- 15141480
TI  - Fast NMR evaluation of lipids in human tissues.
AB  - 1H and 13C NMR spectroscopy was used to evaluate the degree of unsaturation and
      the cholesterol/cholesteryl ester ratio on the total lipid fractions obtained
      from human renal and cerebral tissues. The unsaturated/saturated fatty acid ratio
      was determined in the 13C NMR spectra from the ratio of the integrated areas of
      the resonances at 14.13 and 14.17 ppm assigned to the terminal methyl groups of
      saturated and unsaturated FA, respectively, and is validated by the traditional
      but time consuming gas-chromatographic analysis. Cholesteryl esters are easily
      discriminated in the total lipid fraction extracted from human tissues by means
      of the well-resolved component at 0.99 ppm (1H NMR spectra) of the resonance at
      about 1.00 ppm generally assigned to free cholesterol. The role of NMR
      spectroscopy in the study of lipidic biochemistry of human tissues is confirmed.

PMID- 15141481
TI  - Proteomic characterization of a wild-type wine strain of Saccharomyces
      cerevisiae.
AB  - Saccharomyces cerevisiae is the optimal eukaryotic model system to study
      mammalian biological responses. At the same time Saccharomyces cerevisiae is also
      widely utilized as a biotechnological tool in the food industry. Enological
      Saccharomyces cerevisiae strains have been so far routinely analyzed for their
      microbiological aspects. Nevertheless, wine yeasts are gaining an increasing
      interest in the last years since they strongly affect both the vinification
      process and the organoleptic properties of the final product wine. The protein
      repertoire is responsible of such features and, consequently, 2D-PAGE can be an
      useful tool to evaluate and select optimal wine yeast strains. We present here
      the first proteomic map of a wild-type wine Saccharomyces cerevisiae strain
      selected for the guided fermentation of very high quality wines.

PMID- 15141482
TI  - Structural insights in the folding of small single-domain proteins.
AB  - Understanding the mechanism by which a polypeptide chain folds into its unique
      native structure requires a complete and detailed description of the structural
      and dynamic properties of all the species populated in the folding process. In
      the case of small single domain proteins, experimental studies are defining the
      structures of denatured states, folding intermediates and transition states at
      nearly atomic resolution. Further, the synergy between theoreticians and
      experimentalists is now allowing the detailed description of whole (un)folding
      pathways. Here, we discuss some of the general structural aspects of the
      denatured states, folding intermediates and transition states that are beginning
      to emerge from these studies.

PMID- 15141483
TI  - What the use of disease-unrelated model proteins can tell us about the molecular
      basis of amyloid aggregation and toxicity.
AB  - Recent advances in the studies on protein aggregation have led to a reappraisal
      of the concepts underlying this process. The data reported in the last few years
      showing that protein aggregation into assemblies of amyloid type can be
      considered a generic property of the polypeptide chains suggest that protein
      aggregation in cells can be a more common phenomenon than previously believed.
      Furthermore, the findings that aggregates of disease-unrelated proteins display
      the same cytotoxicity as those formed by proteins and peptides associated with
      disease suggest that toxicity is a consequence of the common structure of
      aggregates and that, at least in most cases, it proceeds by impairing common
      cellular parameters such as free Ca2+ and ROS levels. The new view that
      aggregation of polypeptide chains and aggregate toxicity are not linked to
      specific amino acid sequences rises dramatically the number of sequences one can
      investigate to assess the molecular features underlying protein aggregation and
      the molecular basis of aggregate toxicity. In addition, it rises intriguing
      considerations on protein and cell evolution as well as on amyloid disease
      pathogenesis.

PMID- 15141484
TI  - Nutritional antioxidants and the heme oxygenase pathway of stress tolerance:
      novel targets for neuroprotection in Alzheimer's disease.
AB  - Oxidative stress has been implicated in mechanisms leading to neuronal cell
      injury in various pathological states of the brain. Alzheimer's disease (AD) is a
      progressive disorder with cognitive and memory decline, speech loss, personality
      changes and synapse loss. Many approaches have been undertaken to understand AD,
      but the heterogeneity of the etiologic factors makes it difficult to define the
      clinically most important factor determining the onset and progression of the
      disease. However, increasing evidence indicates that factors such as oxidative
      stress and disturbed protein metabolism and their interaction in a vicious cycle
      are central to AD pathogenesis. Brains of AD patients undergo many changes, such
      as disruption of protein synthesis and degradation, classically associated with
      the heat shock response, which is one form of stress response. Heat-shock
      proteins are proteins serving as molecular chaperones involved in the protection
      of cells from various forms of stress. Recently, the involvement of the heme
      oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has
      received considerable attention, as it has been demonstrated that the expression
      of HO is closely related to that of amyloid precursor protein (APP). HO
      induction, which occurs together with the induction of other HSPs during various
      physiopathological conditions, by generating the vasoactive molecule carbon
      monoxide and the potent antioxidant bilirubin, represents a protective system
      potentially active against brain oxidative injury. Given the broad cytoprotective
      properties of the heat shock response there is now strong interest in discovering
      and developing pharmacological agents capable of inducing the heat shock
      response. Recently, increasing interest has been focused on identifying dietary
      compounds that can inhibit, retard or reverse the multi-stage pathophysiological
      events underlying AD pathology. Alzheimer's disease, in fact, involves a chronic
      inflammatory response associated with both brain injury and beta-amyloid
      associated pathology. Spice and herbs contain phenolic substances with potent
      antioxidative and chemopreventive properties, and it is generally assumed that
      the phenol moiety is responsible for the antioxidant activity. In particular,
      curcumin, a powerful antioxidant derived from the curry spice turmeric, has
      emerged as a strong inducer of the heat shock response. In light of this finding,
      curcumin supplementation has been recently considered as an alternative,
      nutritional approach to reduce oxidative damage and amyloid pathology associated
      with AD. Here we review the importance of the heme oxygenase pathway in brain
      stress tolerance and its significance as antidegenerative mechanism operating in
      AD pathogenesis. We also discuss the role that exogenous antioxidant
      supplementation, conceivably, could play in AD in combating oxidative damage and
      compensating for the decreased level of endogenous antioxidants. Conceivably,
      dietary supplementation with vitamin E or with polyphenolic agents, such as
      curcumin and its derivatives, can forestall the development of AD, consistent
      with a major "metabolic" component to this disorder. Such an outcome would
      provide optimism that the signs and symptoms of this devastating brain disorder
      of aging may be largely delayed and/or modulated.

PMID- 15141485
TI  - [Prevention--a supermarket?].

PMID- 15141486
TI  - [The long night of nursing: key to the world].

PMID- 15141487
TI  - [Xth Oncologic Nursing Congress of the Conference of Oncologic Diseases: assuming
      responsibility].

PMID- 15141488
TI  - [Study of incidence of decubitus ulcer: skin care with effectiveness].

PMID- 15141489
TI  - [The Bobath concept today: still appropiate yesterday--a nursing error today?].

PMID- 15141490
TI  - [Nurse counseling: autonomy and environment of patients form the basis].

PMID- 15141491
TI  - [Health promotion--a personal responsibility nursing task? "It provides the basis
      for development of the profession" (interview by Alfred Dorfmeister)].

PMID- 15141492
TI  - [Nurse counseling of diabetic patients according to the disease management
      program (DMP): ethical care also means evidence-based care].

PMID- 15141493
TI  - [Postoperative use of elastic stockings to prevent thrombosis: what is most
      effective].

PMID- 15141494
TI  - [Body image after mastectomy: the end of physical intactness].

PMID- 15141495
TI  - [Family and professional nursing: back to a new equilibrium].

PMID- 15141496
TI  - [Presentation of statistical data in nursing 4--bar graphs: variations for group
      comparison].

PMID- 15141497
TI  - [European Nursing Care Pathways (ENP): from general practice for general nursing
      practice].

PMID- 15141499
TI  - [Primary nursing and case management: facilitating transitions].

PMID- 15141498
TI  - [Strategy-oriented salary and incentive system: from classical hourly wage to
      performance-oriented payment].

PMID- 15141500
TI  - [Health promotion and salutogenesis: supporting life competences].

PMID- 15141501
TI  - [From case to case: Magdalena's world].

PMID- 15141502
TI  - [Diagnosis: "test anxiety"].

PMID- 15141503
TI  - [Learning support--an example of self-guided learning in nursing education].

PMID- 15141504
TI  - [Model department for practical nursing education].

PMID- 15141505
TI  - [Ten cities in crusade against infantile obesity].

PMID- 15141509
TI  - [Reading for communicating].

PMID- 15141510
TI  - [A book, what a history!].

PMID- 15141511
TI  - [Reading for pleasure with small children].

PMID- 15141512
TI  - [The child, a being of communication].

PMID- 15141513
TI  - [Storytelling for hospitalized children].

PMID- 15141514
TI  - [Ways to read in public assistance hospitals of Paris].

PMID- 15141515
TI  - [Drawing is writing].

PMID- 15141516
TI  - [Role guidelines for the pediatric aides].

PMID- 15141517
TI  - [1/5, The responsibility of nurses aides before an administrative judge].

PMID- 15141518
TI  - [III--differed emergencies. 4/. Upper anorectal abnormalities].

PMID- 15141519
TI  - [Screening for hemolytic streptococcus group B in pregnancy and prevention of
      infection in neonates].
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of Group B
      streptococcus (GBS) screening and intrapartum antibiotic prophylaxis to the
      incidence of GBS disease in newborns. DESIGN: Prospective non-randomised study.
      SETTING: IInd Clinic of Obstetric and Gynaecology LFUK and FNsP Ruzinov,
      Bratislava, Slovakia. METHODS: We enrolled 3023 newborns (754 in the study group,
      2269 in the control group), which were born between 1.9.2000 and 31.3.2003. In
      both groups we compared following variables: total number of infectious diseases
      in newborns, number and forms of GBS neonatal disease, number of perinatal death
      due to GBS disease. RESULTS: There was no GBS disease in the study group of 754
      newborns. Mothers of these newborns had one screening culture in 35-36th week of
      gestation. One swab was taken from vagina and anus. GBS carriers (161-21.4%) were
      administered i.v. intrapartum antibiotic prophylaxis with Penicillin G i.v., or,
      when allergy to penicillin was in history, with Clindamycin i.v. In the control
      group of 2269 newborns, whose mothers had no prevention, the incidence of GBS
      neonatal disease reached 7.5/1000 newborns (17 cases). The incidence of invasive
      GBS neonatal disease was 2.6/1000 newborns. CONCLUSION: The authors have noticed
      a significant decrease in incidence of GBS neonatal disease after implication of
      GBS screening and intrapartum antibiotic prophylaxis.

PMID- 15141520
TI  - [Comparison of the cost of treatment of premature labor with atosiban or beta
      sympathomimetics from the perspective of the health care payer--a
      pharmacoeconomic model].
AB  - OBJECTIVE: To evaluate the cost of treating premature delivery with atosiban or
      beta-sympatomimetic drugs (fenoterol and hexoprenalin) from the perspective of
      health care payer--the medical insurance company. DESIGN: A pharmaco-economic
      model based on the results of randomized, controlled clinical study. SETTING:
      Hospital Pharmacy at Vitkovice Hospital of Blessed Mary Antonia, Ostrava.
      METHODS: The study is based on the application of clinical decision-making
      analysis, which includes results of a randomized controlled clinical study as
      well as data on the cost of clinical interventions and cost of drug therapy. The
      pharmaco-economic model was created from the perspective of the payer of health
      care--the insurance company. This model presumes the administration of atosiban
      or beta-sympatomimetic drugs (fenoterol and hexoprenalin) for the period of 18
      and 48 h and the therapy of possible untoward effects for the next 72 h after the
      administration of the drugs. The analysis of sensitivity of pharmacokinetic model
      also employs so called low and high estimate of supplementary cost for the
      treatment of untoward effects. RESULTS: After the administration of the drugs for
      the period of 18 h the total cost of the payer of medical care was in the range
      of 21,914.5-21,974.4 CKr in atosiban, 19,878.7-22,661.4 CKr in fenoterol and
      19,942.9-21,974.4 CKr in hexoprenalin. In the administration of the drugs for 48
      h, the overall cost of the payer of medical care was in the range of 43,082.5
      43,142.4 CKr in atosiban, 19,960.3-23,150.7 CKr in fenoterol and 20,131.3
      23,574.0 in hexoprenalin. CONCLUSIONS: This study compared overall cost
      associated with hospitalization of a premature delivery from the perspective of
      the medical care payer, i.e. the health insurance company. The authors applied a
      pharmaco-economic model evaluating hospitalization for the period of 48 h and
      subsequent therapy of possible untoward effects for the period of up to 72 h. In
      case of a shorter administration of atosiban (up to 18 h) the overall cost of
      hospitalization for premature delivery for the period of 48 h from the point of
      view of medical insurance company is basically comparable with the administration
      of beta-sympatomimetic drugs. If atosiban is administered for more than 18 h, the
      overall cost of hospitalization is higher than with beta-sympatomimetic drugs,
      and the cost increases in relation to the duration of atosiban administration.

PMID- 15141521
TI  - [Prophylactic adnexectomy].
AB  - OBJECTIVE: Analysis of the issue of prophylactic bilateral salpingo-oophorectomy
      (BSO): a) during pelvic surgery for benign diagnosis; b) in women with hereditary
      risk of ovarian cancer. DESIGN: Review article. SETTING: Department of Obstetric
      and Gynecology, Charles University. METHODS: Critical review of published data.
      CONCLUSION: During pelvic surgery for benign diagnosis a prophylactic BSO is
      indicated of the age over 45, in younger women an individual approach is
      required, considering many aspects, including history of ovarian and breast
      cancer. Another indication for BSO is an increased risk of familial ovarian
      cancer. The surgery significantly diminished the risk of epithelial cancer of
      ovary, fallopian tube, and simultaneously the risk of breast cancer. There is a
      continuing increased risk of peritoneal cancer following the surgery. Bilateral
      oophorectomy together with bilateral salpingectomy is recommended. The age limit
      for surgery is about 35 years after careful consideration of individual risk,
      reproductive plans, type of mutation and age at malignant disease manifestation
      in previous generation. Potential alternative for women who do not accept
      prophylactic surgery is tubal ligation. Screening of risk group or
      chemoprevention by oral contraceptives are not equivalent alternatives to
      prophylactic surgery.

PMID- 15141522
TI  - [History of registration of prenatally and postnatally diagnosed congenital
      defects in the Czech Republic].
AB  - OBJECTIVE: Analysis of incidence of birth defects in general and the proportion
      of individual types of birth defects within the framework of registration of
      inborn defects in the period of 1961-2000 in the Czech Republic. DESIGN: A
      retrospective analysis based on registered birth defects from the material of
      Institute of Care for Mother and Child and IHIS from the period of 1961-2000.
      METHODS: The authors compared the real frequency of birth defects in the eighties
      and nineties with expected frequency calculated on the basis of mean values from
      the sixties and seventies. RESULTS AND CONCLUSIONS: The results between the
      expected and estimated values of the overall frequency of birth defects are based
      on two reasons. First of all there are changes in registration as such--increased
      numbers of registered types of birth defects, prolonged period of reporting the
      inborn defects up to 15 years old children, decreased levels of foetus viability
      and other factors. There is also the change of frequency caused by all-population
      changes (eradication of some infections, vaccination rate in the population,
      improved nutrition of the population, year-around availability of vitamins), the
      development of diagnostic methods (ultrasonographic methods) and, especially, the
      role of prenatal screening and prenatal diagnostic methods in practice.

PMID- 15141523
TI  - [Hysterectomy at the Olomouc Clinic 1989-2002: evolution in the indication
      spectrum and surgical approach].
AB  - OBJECTIVE: Analysis of representation in surgical approaches and techniques to
      hysterectomy (abdominal hysterectomy, vaginal hysterectomy, laparoscopically
      assisted vaginal hysterectomy) in our clinic. The evolution of indications,
      diagnosis and operating approaches from 1989 to 2002 were analysed. DESIGN:
      Retrospective study. SETTING: Department of Obstetric and Gynecology, University
      Hospital, Olomouc. METHODS: Retrospective analysis of medical documentation
      (operating protocols). RESULTS: 3079 hysterectomies were performed in years 1989
      2002. Type of hysterectomy in years 1989-1993: abdominal approach 97% (diagnosis:
      uterine leiomyomas 57%, malignant tumors 28%), vaginal hysterectomy 3%
      (diagnosis: descensus uteri only). Type of hysterectomy in years 1989-1993:
      abdominal approach 42% (diagnosis: malignant tumors 65%, uterine leiomyomas 28%),
      vaginal hysterectomy 48% (diagnosis: uterine leiomyomas 56%, descensus uteri
      25%), Laparoscopically assisted vaginal hysterectomy (LAVH) 10%. CONCLUSION:
      Decreased number of abdominal hysterectomies in women with non oncological
      diagnosis since 1989 to 2002 and increase of vaginal hysterectomies and LAVH was
      noted. This complies with the contemporary trends of minimally invasive surgery.

PMID- 15141524
TI  - [Effect of hypothermia on lactate dehydrogenase activity in blood and the
      cerebral cortex in 14-day-old and adult laboratory rats].
AB  - OBJECTIVE: In the following study, possible protective effect of hypothermia (of
      various degree) on brain cortex metabolic activity in very young animals and
      adult rats was examined. DESIGN: Experimental study. SETTING: Institute of
      Physiology, 1st Med. Faculty, Charles University, Prague, Czech Republic.
      METHODS: Homogenates of brain cortex of 14-day-old and adult rats and
      simultaneously blood serum were examined for lactate-dehydrogenase activity
      (LDH), [E.C. 1.1.1.27]. Three variously tempered incubation media (38 degrees C =
      control values, 30 degrees C = mild hypothermia, 22 degrees C = strong
      hypothermia) were checked. Also the adult rats (90-120 days) were examined (in
      the same arrangement). RESULTS: The LDH activity in the blood serum of 14-day-old
      rats under hypothermic condition was unchanged as compared with control values.
      In their brain cortex the hypothermia evokes a significant changes in LDH
      activity (mukat/l). In adult rats the results are different: no significant
      changes in LDH activity in the brain cortex under hypothermic condition were
      found, but significant drop in mentioned enzyme activity in the blood serum was
      established. Finally: in young animals the starting LDH activity in the blood
      serum as well as in the brain cortex was always significantly higher as compared
      with values found in adult animals. CONCLUSION: The starting higher LDH activity
      in the blood serum as well as in the brain cortex in young rats (as compared with
      adults) and the different feature of LDH changes under hypothermic conditions are
      considered and discussed especially with the possibility of protective action of
      hypothermia in hypoxic and asphyxic newborns.

PMID- 15141525
TI  - [Antifungal immunity and its mechanism in female genitalia].
AB  - OBJECTIVE: A review of immunological aspects of fungal infections with focus on
      vulvovaginal candidiasis. DESIGN: Review. SETTING: Department of Obstetrics and
      Gynaecology, Medical Faculty, Hradec Kralove, Charles University in Prague,
      Department of Biological and Medical sciences, Faculty of Pharmacy, Hradec
      Kralove, Charles University in Prague, Department of Clinical Immunology and
      Allergology, University Hospital, Hradec Kralove, Department of Clinical
      Microbiology, University Hospital, Hradec Kralove. SUBJECT AND METHOD: Survey and
      discussion of current immunological aspects of vulvovaginal candidias based on
      literature review and personal experience. CONCLUSION: The current knowledge of
      immunity to Candida vulvovaginitis, particularly from experimental studies on
      animal models, support a more relevant role of local protection mechanisms than
      systemic immunity. As a consequence of this compartmentalization of the immune
      response, the role of innate and adaptive immunity remains unclear. The
      development of vulvovaginal candidiasis depends on a number of factors, including
      both the individual predisposition of a macroorganism and the properties of a
      fungal strain, and the environmental conditions influencing a delicate balance
      between the host and the yeast.

PMID- 15141526
TI  - [The hiatus urogenitalis and its dorsal component--its importance in urinary and
      fecal continence in women].
AB  - OBJECTIVE: Numerous anatomical studies over the last years resulted in a
      principal shift in the view of the area of female pelvic floor. These studies
      also deal with the area of posterior compartment, i.e. a region which used to be
      of little interest to urogynecologists. This article presents a brief outline of
      anatomical and physiological knowledge as well as a brief survey of most
      important methods of examination and basic clinical symptoms associated with
      disorders of posterior part of hiatus urogenitalis. The presently accepted
      concept of a complex approach to disorders of female pelvic floor will probably
      require increased interest in this area among urogynecologists. The article is
      aimed at summarizing elementary knowledge necessary for adequate clinical care of
      patients suffering from disorder in posterior compartment function. SUBJECT:
      Review article. SETTING: Department of Gynecology and Obstetric, Faculty Hospital
      Na Bulovce, 1st Medical Faculty, Prague, Czech Republic.

PMID- 15141527
TI  - [Occurrence and survival in children with selected types of congenital defects in
      the Czech Republic 1994-2001. Part 2].
AB  - OBJECTIVE: Analysis of prenatal and postnatal incidence of selected types of
      birth defects in the Czech Republic in the period of 1994-2001. In the
      postnatally diagnosed cases the survival in the course of the first year of life
      was analyzed. Selected birth defects--omphalocele, gastroschisis, abdominal wall
      defects, renal agenesis and hypoplasie, cystic kidney disease, diaphragm hernia.
      TYPE OF STUDY: Retrospective analysis from registry of birth defects in the
      Institute of Health Information and Statistie of the Czech Republic in the period
      of 1994-2001. METHOD: The authors analyzed frequency of prenatally and
      postnatally diagnosed cases of 6 selected types of birth defects in the period of
      1994-2001 in the Czech Republic. In cases where the diagnosis was established
      after birth, analysis of survival and death rate during the first year of life
      was performed for selected birth defects. RESULTS: In the period of 1994-2001,
      745,410 children were born in the Czech Republic. There were 22,711 children with
      one or more birth defects diagnosed in this cohort during the first year of life.
      The mean incidence of all cases in this period of observation was 304.52 per
      10,000 live born children. The percentage of prenatally diagnosed cases, ended
      for this diagnosis in the above mentioned period of observation, was 66% in
      abdominal wall defects, 55% in omphalocele and 77% in gastroschisis. In cases
      where the diagnosis was established after birth, 93.55% of children survived the
      first year of life. In cases of birth cystic kidney 25% were diagnosed prenatally
      and ended for renal agenesis and hypoplasie of the kidneys and 27% due to cystic
      kidney. In cases of diaphragmatic hernia, 31% of cases were diagnosed an ended
      prematurely after positive prenatal diagnosis, and about one third of affected
      children died during the first year of life. CONCLUSION: Incidence of these types
      of birth defects in newborns in the Czech Republic is presently lower than in
      previous years particularly due to successful prenatal diagnostics. Cases where
      the diagnosis is established after delivery represent an important part of
      perinatal, neonatal and post-neonatal mortality and morbility.

PMID- 15141528
TI  - [The WHO classification of epithelial tumors of the uterine cervix (2003).
      Comment on the new classification].

PMID- 15141529
TI  - Cardiac rehabilitation nurses: mending hearts.

PMID- 15141530
TI  - Leading a multi-generational workforce.

PMID- 15141531
TI  - Putting it all together.

PMID- 15141533
TI  - The logic of integration.

PMID- 15141532
TI  - Choosing the best slip-resistant shoe.

PMID- 15141534
TI  - Improving your drug testing ROI.

PMID- 15141535
TI  - How quickly can we respond?

PMID- 15141536
TI  - Thermal imagers for industrial fire brigades.

PMID- 15141537
TI  - Measuring adjustability's benefits.

PMID- 15141538
TI  - Using BBS in training programs.

PMID- 15141539
TI  - The science of safety.

PMID- 15141540
TI  - Effective exposure control.

PMID- 15141541
TI  - 'Handle with care'. More of us are reading labels and checking out possible side
      effects, but we still have far to go.

PMID- 15141542
TI  - From the inside out.

PMID- 15141543
TI  - Attuned to the language of business.

PMID- 15141544
TI  - Acute pulmonary histoplasmosis.

PMID- 15141545
TI  - Evaluation of anomalous coronary artery anatomy using multi-detector CT.
AB  - OBJECTIVE: Anomalous coronary vessels can result in sudden cardiac death.
      Coronary angiography is typically used to make the diagnosis; however, other
      modalities have been used, including transesophageal Doppler ultrasound, MRI,
      electron beam CT, and helical CT. We report two cases of evaluation of anomalous
      coronary vessels using multi-detector CT without cardiac gating. CONCLUSION: Our
      experience suggests that multi-detector CT with its rapid scanning time, superior
      spatial resolution, and wide availability could make it a viable tool in the
      evaluation of anomalous coronary anatomy in angiographically equivocal cases.

PMID- 15141546
TI  - The social impact of medicine. Chapter 18.

PMID- 15141547
TI  - [The family with rucksacks].

PMID- 15141548
TI  - [Family-centered nurses. The relatives are the experts].

PMID- 15141549
TI  - [Interview with Barbara Preusse-Bleuler and Susanne Eckert-Dreyer. "Empowerment
      for our nurses"].

PMID- 15141550
TI  - [Pertaining to integration. Accusatory pranks and advice].

PMID- 15141551
TI  - [Rationalization. The "remedy" as overkill].

PMID- 15141552
TI  - [Interview with Pierre Gobet. "Professional quality standards are in questionS"].

PMID- 15141553
TI  - [Five years after the "manifest" . Debate on rationing: from acute to chronic].

PMID- 15141554
TI  - [Hydrochloric acid attack in women: s devastating throat appetite].

PMID- 15141555
TI  - [Long-term nursing. Quality requires cooperative understanding].

PMID- 15141556
TI  - [These chemicals].

PMID- 15141558
TI  - [Examining one's own dreams].

PMID- 15141557
TI  - [Martin Lysser. "Extreme situations fascinate me"].

PMID- 15141559
TI  - [If Diogenes knew].

PMID- 15141560
TI  - [Preparation, Attention and Support Society. Children have the right to know].

PMID- 15141561
TI  - [Diogenes syndrome. What does the accumulation of waste matter?].

PMID- 15141562
TI  - [Live your emotions in a creative manner. Discover you interior clown].

PMID- 15141563
TI  - ["The clown is a social actor"].

PMID- 15141564
TI  - [Use of virtual internet services. Are we prepared for E-health?].

PMID- 15141566
TI  - ["Most important: protect the contact with the patient"].

PMID- 15141565
TI  - [Geriatric rehabilitation. Decision to escape: an agreement to find].

PMID- 15141567
TI  - [Involving the family].

PMID- 15141568
TI  - [Calls in long term care. Greater autonomy and time savings].

PMID- 15141569
TI  - [In Africa as caregiver: "The presumption should remain at home"].

PMID- 15141570
TI  - Are you running a "risky" business.

PMID- 15141571
TI  - Home care & hospice find a champion in Barbara Boxer.

PMID- 15141572
TI  - Patient admission, service, and discharge: rules to survive by.

PMID- 15141573
TI  - "But it was only a gift...". OIG gift restrictions.

PMID- 15141574
TI  - Too hot to handle: burn prevention for home care & hospice clients.

PMID- 15141575
TI  - Watch your step! Preventing falls in the home.

PMID- 15141576
TI  - Managing your risk by managing your staff. Tips on hiring and retaining
      responsible employees.

PMID- 15141577
TI  - Income tax breaks for caregivers: know your entitlements.

PMID- 15141578
TI  - Home care payment changes in a post-BBA world.

PMID- 15141579
TI  - Conveying values, mission, and vision.

PMID- 15141580
TI  - Certified nursing assistants' "bridge" to home care.

PMID- 15141581
TI  - 21 reasons home care pays.

PMID- 15141582
TI  - Moving closer to an NHII reality.

PMID- 15141583
TI  - Building the National Health Information Infrastructure.

PMID- 15141584
TI  - Santa Barbara blueprint. A regional health data network takes the plunge.

PMID- 15141585
TI  - Canada hits the infoway. How Canada is transforming its HIM infrastructure.

PMID- 15141586
TI  - What CFOs want.

PMID- 15141587
TI  - Forgiveness means never having to say you're not insured.

PMID- 15141588
TI  - Data synch. Aligning US data exchange initiatives.

PMID- 15141589
TI  - Practice brief. Securing wireless technology for healthcare.
AB  - Wireless networking can be a very complex science, requiring an understanding of
      physics and the electromagnetic spectrum. While the radio theory behind the
      technology can be challenging, a basic understanding of wireless networking can
      be sufficient for small-scale deployment. Numerous security mechanisms are
      available to wireless technologies, making it practical, scalable, and affordable
      for healthcare organizations. The decision on the selected security model should
      take into account the needs for additional server hardware and administrative
      costs. Where wide area network connections exist between cooperative
      organizations, deployment of a distributed security model can be considered to
      reduce administrative overhead. The wireless approach chosen should be dynamic
      and concentrate on the organization's specific environmental needs. Aspects of
      organizational mission, operations, service level, and budget allotment as well
      as an organization's risk tolerance are all part of the balance in the decision
      to deploy wireless technology.

PMID- 15141590
TI  - The HIPAA security shopping list.

PMID- 15141591
TI  - In case of a crash ... computer backups.

PMID- 15141592
TI  - Coding and HIM in home care: up to the challenge.

PMID- 15141593
TI  - PPS brings change to inpatient psychiatric facilities.

PMID- 15141594
TI  - Laying the foundation for the NHII.

PMID- 15141595
TI  - Live donor liver transplantation: is this really the way liver transplantation
      should be developed in India?

PMID- 15141596
TI  - Road traffic deaths and injuries in India: time for action.

PMID- 15141597
TI  - Differentiation of human nasopharyngeal carcinoma xenografts and repression of
      telomerase activity induced by arsenic trioxide.
AB  - BACKGROUND: Arsenic trioxide (As2O3) induced apoptosis and differentiation of
      acute promyelocytic leukaemia. A few in vivo experimental investigations of its
      efficacy in solid tumours have been done. This study was designed to explore the
      differentiation-inducing effect, and the possible mechanisms involved, of As2O3
      on human nasopharyngeal carcinoma CSNE-1 xenografts. METHODS: Nasopharyngeal
      carcinoma cell CSNE-1 was established as a xenograft in nude mice. The tumour
      bearing mice were treated with As2O3 at a dose of 5 mg/kg/day. To assess tumour
      differentiation, tumour growth was observed and histological changes were
      analysed under light and electron microscopy. Expression of latent membrane
      protein 1 (LMP1) and cytokeratin 4 (CK4) was determined by immunohistochemistry.
      A PCR-based telomeric repeat amplification protocol assay (TRAP-ELISA) was used
      to measure telomerase activity. RESULTS: The xenografts underwent
      differentiation. LMP 1 of the cells decreased significantly and there was a
      pronounced decline in telomerase activity. CONCLUSION: As2O3 can inhibit
      xenograft growth and induce morphological and functional differentiation of CSNE
      1 cells. The As2O3-induced differentiation was associated with downregulation of
      telomerase activity.

PMID- 15141598
TI  - Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic
      phase following conditioning with busulphan and cyclophosphamide: a follow up
      report.
AB  - BACKGROUND: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem
      cell transplantation remains the only modality of treatment that can eradicate a
      leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML).
      However, the advent of the targeted molecule imatinib mesylate (formerly STI-571)
      against the bcr-abl chimeric protein in the disease has brought the issue of
      managing newly diagnosed CML patients, especially those with available donors, to
      the crossroads. Although the curative potential of this agent remains unknown, it
      can produce complete cytogenetic response in > 60% of newly diagnosed patients.
      METHODS: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase
      patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as
      a conditioning regimen. All patients received human leucocyte antigen (HLA)
      identical sibling donor haematopoletic stem cells--bone marrow in 41 patients
      (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant
      prophylaxis for graft-versus-host disease included a short course of methotrexate
      (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients
      (69.1%), while a combination of cyclosporin and methylprednisolone was used in
      the remaining 17 (29%). RESULTS: At a median follow up of 48 months (10-144
      months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17
      patients (30.9%). Acute graft-versus-host disease developed in 37 patients
      (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease
      developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till
      date. The leukaemia-free survival is 64.3% in the peripheral stem cell group,
      whereas it is 41.5% in the bone marrow recipient group. CONCLUSION: Allogeneic
      BMT appears to result in eradication of CML and ensure disease-free survival in
      about half the patients. However, efforts should be made to prevent graft-versus
      host disease and minimize early mortality.

PMID- 15141599
TI  - Deaths due to road traffic crashed in Hyderabad city in India: need for
      strengthening surveillance.
AB  - BACKGROUND: Road traffic crashes are an important cause of death and disability
      in India. Reliable and accurate data are necessary to plan strategies to reduce
      death and disability due to road traffic crashes. We assessed the utility of the
      available data on deaths due to road traffic crashes for road crash surveillance
      for a major metropolitan city of southern India. METHODS: We analysed the
      Department of Police database on deaths due to road traffic crashes for 2002 in
      Hyderabad, southern India and collected data from a leading newspaper for the
      same information using a standardized format. RESULTS: A total of 3039 cases of
      road traffic crashes were recorded in the police database for 2002, including 400
      cases (13.2%) in which 411 people were killed. In the same year, 316 cases of
      road traffic crashes resulting in 353 deaths were reported in the newspaper. The
      majority of those who died due to these crashes were males. Seventy per cent of
      those killed were between 16 and 49 years of age. Pedestrians and riders of two
      wheelers were the most vulnerable. Collision with a vehicle caused 86.4% of all
      crashes and 60% of the victims died before reaching a hospital. The available
      data were not comprehensive enough to provide a thorough basis for planning
      intervention strategies to reduce fatalities due to road crashes. CONCLUSION:
      Despite the gaps in reporting of fatalities in road traffic crashes in these data
      sources, they provide insights into the magnitude and nature of deaths resulting
      from such crashes in Hyderabad. The available data have limitations and there is
      a need for strengthening the road traffic crash surveillance system to have
      reliable, accurate and adequate data on road traffic crashes and the resulting
      fatalities and injuries. These could then form the basis for planning effective
      intervention strategies to improve road safety.

PMID- 15141600
TI  - Pharmacoeconomics.
AB  - Pharmacoeconomics focuses on the costs and benefits of drug therapy and
      pharmacoeconomic evaluations provide a basis for resource allocation and
      utilization. It is increasingly becoming important for health policy decision
      making. A pharmacoeconomic evaluation may be conducted as an economic assessment
      incorporated into clinical trials. Such trials should compare the new
      drug/procedure with an older drug or existing intervention. Four techniques are
      used for economic evaluation, namely, cost-minimization analysis, cost
      effectiveness analysis, cost-utility analysis and cost-benefit analysis. The
      choice of the evaluation method depends on the nature of outcomes and the context
      in which the choices need to be made. Pharmacoeconomics is a young science that
      will improve with application. Its need is undeniable, especially in developing
      countries.

PMID- 15141601
TI  - Chemotherapy for peripheral neuroectodermal tumours of the bone.

PMID- 15141602
TI  - Systematic reviews and meta-analyses: an illustrated, step-by-step guide.
AB  - Systematic reviews and meta-analyses synthesize data from existing primary
      research, and well-conducted reviews offer clinicians a practical solution to the
      problem of staying current in their fields of interest. A whole generation of
      secondary journals, pre-appraised evidence libraries and periodically updated
      electronic texts are now available to clinicians. However, not all systematic
      reviews are of high quality, and it is important to be able to critically assess
      their validity and applicability. This article is an illustrated guide for
      conducting systematic reviews. A clear understanding of the process will provide
      clinicians with the tools to judiciously appraise reviews and interpret them. We
      hope that it will enable clinicians to conduct systematic reviews, generate high
      quality evidence, and contribute to the evidence-based medicine movement.

PMID- 15141603
TI  - Galvanizing mental health research in low- and middle-income countries: role of
      scientific journals.

PMID- 15141604
TI  - In defence of live operative workshops.

PMID- 15141605
TI  - Live operative workshops: a critique.

PMID- 15141606
TI  - Nurses and ethics.

PMID- 15141607
TI  - The choice of poor patients.

PMID- 15141608
TI  - Teaching scientific methodology at a medical school: experience from Split,
      Croatia.

PMID- 15141610
TI  - Sexual health.

PMID- 15141609
TI  - Intensive care in Australia and New Zealand: past, present and future.

PMID- 15141611
TI  - What's in a name--25(OH)D or 25(OH)D3?

PMID- 15141612
TI  - Body mass index, waist circumference and waist-hip ratio: findings from an urban
      community survey, Tamil Nadu.

PMID- 15141613
TI  - Scientific writing skills of medical personnel in India: an evaluation.

PMID- 15141614
TI  - In vitro activity of vancomycin and teicoplanin against staphylococci in
      intensive care units.

PMID- 15141615
TI  - [Present day problems in the elaboration of documents regulating sanitary
      epidemiological safety of children and adolescents].
AB  - The drastic urbanization of modern society, the wide use of new teaching methods
      and programs at the educational establishments, the emergence of new types of pre
      school educational institutions (PEI), the change of age-specific composition of
      children in both PEI and educational establishments require that new documents on
      the basic types of educational establishments should be worked out. The financing
      of work into preparing sanitary legislative documents has not been solved so far.
      In connection with the adoption of the Federal Law "On Technical Regulation",
      while preparing the technical regulations, society is to guarantee a child the
      development environment, good growth conditions, including the optimum level of
      functions.

PMID- 15141616
TI  - [Study of the influence of chemical pollution of the environment on the health
      status of children by noninvasive biochemical diagnosis].
AB  - The paper presents the results of a complex biochemical study of the health
      status of children from Moscow, the Moscow Region, Yaroslavl, Cherepovets, the
      Voronezh Region, etc. The presented results allowed the authors to detect renal
      protective dysfunction in children in relation to environmental pollution. The
      greatest deviations of the studied parameters were observed in Moscow (Garden
      Ring, Central Administration Okrug (CAO)) and in the industrial town of
      Cherepovets (the area in vicinity of the Severostal enterprise). The results of a
      complex biomedical examination of 486 children in the Moscow CAO were first
      analyzed. The spread of changes was established in the studied parameters over a
      time, which indicates the presence of immunodeficiency, immunopathology, renal
      detoxifying dysfunction, and nasal and oral mucosal changes.

PMID- 15141617
TI  - [Effects of chemical substances polluting ambient air of cities and towns on
      reproductive health (review of literature)].

PMID- 15141618
TI  - [Effects of waste water sediments on the levels of heavy metals ion the soil and
      plants].
AB  - Field small-plot experiments studied the effects of sediments of waste water from
      Saransk disposal systems. The content of toxic heavy metals (lead, arsenic, and
      cadmium) in the waste-water sediments, was shown to be not greater than their
      maximum permissible concentrations (32, 2, and 10 mg per kg of dried soil,
      respectively). With the use of waste-water sediments, the content of manganese,
      copper, tin, nickel, vanadium, beryllium, cobalt, iron, and chromium was found to
      correspond to their baseline level in the soil and plants.

PMID- 15141619
TI  - [Safety and physiological value of drinking water in the centralized water supply
      system in the Republic of Adygeya].

PMID- 15141620
TI  - [Current issues in the organization of sanitary safe areas of industrial
      enterprises and other areas in the Russian Federation].

PMID- 15141621
TI  - [Biochemical evaluation of urban soils (in case of Kemerovo)].
AB  - The study has revealed common changes in the chemical composition of soils in the
      town of Kemerovo. Under urban conditions, there is a reduction in pH, an increase
      in the carbonate properties of soil mineral part and in the content of exchange
      cations (Ca2+, K+, Na+) in the soil absorptive complex, a decrease in the level
      of gross elements (N, P, K), as well as accumulation of heavy metals (Pb, Cd, Zn,
      Ni, Mn, Co, Fe, Cr) and sulfates. The above changes are determined by the level
      of a technogenic load; and they are more pronounced in the soils located along
      the main roads, particularly in the districts (Kirovsky, Rudnichnyi, and
      Zavodskoy) with heavy traffic of freight transport.

PMID- 15141622
TI  - [Assessment of human health risk due to environmental pollution in the city of
      Orsk].
AB  - The established tense ecological situation in the town of Orsk presents a serious
      human threat. The use of methods for assessing the risk has allowed the authors
      to determine the values of carcinogenic and noncarcinogenic risks. Due to the
      influence of all environments polluted by industrial emissions, the total annual
      carcinogenic risk is 2.31 cases for the adult population of the town and 0.49 for
      its children. The greatest carcinogenic risk is associated with arsenic in water
      and foodstuffs, hexavalent chromium, cadmium, and formaldehyde in the air. The
      high concentrations of dust, phenol, nitrogen dioxide, and carbon oxide cause a
      major damage to human health. The established specific values of this risk are of
      relative significance.

PMID- 15141623
TI  - [Combined effect of detergents and priority pollutants on the body and quality of
      environment (review of literature)].
AB  - The paper deals with the topical problem in the combined effect of detergents and
      priority pollutants (pesticides, mineral fertilizers, and heavy pollutants) on
      the body and the quality of the environment. Under combined man-made
      environmental pollution, surfactants may substantially alter the behavior and
      toxicity of many chemical substances, which requires that these studies should be
      continued.

PMID- 15141624
TI  - [Safety criteria in working with metallic beryllium].
AB  - The concept of an acceptable risk was used to elaborate criteria required to
      analyze the safety of operations with metallic beryllium at dangerous industrial
      enterprises. To follow these criteria ensures the high level of beryllium work
      safety, follows the present-day tendency for the development of approaches to
      evaluating the safety of devices using toxically hazard substances. The criteria
      involve a human death risk due to the single entry of beryllium into the body
      during accidents, as well as the level of its chronic intake in different groups
      of subjects on secondary dust formation after an accident. The accident that
      occurred at the beryllium works, the industrial association "Ulbinsk Metallurgic
      Plant, in Ust-Kamenogorsk on September 12, 1990, has been analyzed by using the
      computer program "GAUSS". The results of calculations are in good agreement with
      those of observations.

PMID- 15141625
TI  - [Hygienic evaluation of the large city environmental chemical pollution influence
      on children's health status].
AB  - The data of hygienic monitoring of the Saint Petersburg environment suggest that
      the soil of the megapolis is greatly polluted with heavy metals among which lead
      is of priority. The studies performed indicate that under the environmental and
      hygienic conditions, the level of lead in the hair of children is a qualitative
      and quantitative criterion for the negative impact of chemical pollution of the
      environment. The threshold level at which there are higher morbidity rates in
      children is 5.8 micrograms/g. The findings suggest that there is a reduction in
      the earlier accepted critical level 8 micrograms/g. (V. Lukovenko, 1990; B.A.
      Revich, 1999). When its level is 8 micrograms/g, the children are found to have
      retarded mental and physical development. The results of examination of the
      nonspecific resistance system in children living under the conditions of the
      megapolis show that the level of nonspecific defense decreases when the hair
      content of lead is 5 micrograms/g.

PMID- 15141626
TI  - [Quantitative evaluation of interaction between toxic substances in overall soil
      pollution].
AB  - A calculation method is proposed to estimate the interaction of toxicants in
      binary and triple mixtures. The types of phytotoxic effects of herbicides and
      their metabolites that are concurrently present in the soil in different
      combinations on crops are considered. Examples of how to calculate the ratio of
      combined effects of phytoxicants, as well as the characteristics of such an
      interaction for specific experimental conditions are given.

PMID- 15141627
TI  - [Hygienic optimization of the use of chemical protective means on railway
      transport].
AB  - The paper presents data characterizing the working conditions of railway workers.
      It shows that there is the greatest levels of noise and vibration, the burden and
      intensity of work. The worst working conditions are noted in energy supply, car,
      locomotive services and track facilities. The working conditions determine a
      significant industrial risk of railway workers since the prevention of health
      abnormalities by using chemical protective means is a topical problem. The
      priority lines of hygienic rationale for optimization the choice and use of
      chemical protective means for workers exposed to occupational hazards are
      determined.

PMID- 15141628
TI  - [Hygienic rationale for the safety of food transportation by railroad].
AB  - The paper presents new requirements for carriage of foodstuffs by rail in Russia.
      It discusses the aspects of environmental safety from possible spilling, leakage,
      scattering, and other emergencies; the matters of health care in those engaged in
      cargo transportation, as well as the preservation of cargoes themselves. The
      basic hygienic requirements that should be met on transportation of foodstuffs;
      the main points of compulsory certification of railway transport vehicles used to
      carry foodstuffs are outlines. Emphasis is laid on the necessity of setting up a
      uniform database for certifying railway vehicles designed for carriage of
      foodstuffs throughout the railway network of Russia.

PMID- 15141629
TI  - [Improvement of air quality at dental practice premises].

PMID- 15141630
TI  - [Physical development of school children in the Volgograd educational system].
AB  - The physical development of schoolchildren living in different man-made load
      areas of Volgograd, a large industrial town and going to different educational
      establishments was studied and evaluated. There were more children with retarded
      biological development and morphofunctional abnormalities in the high man-made
      loaded areas. There were also differences in the physical development of pupils
      from different types of educational establishments: among the pupils of general
      educational schools there were more children with retarded biological development
      and morphofunctional abnormalities. These differences are greater in poor
      ecological areas.

PMID- 15141632
TI  - [Health status of city children].
AB  - The conditions of a megapolis are marked by a considerable man-made pressure and
      environmental denaturalization. When children long live under these conditions,
      they develop a specific response as high rates of morbidity and prevalence of
      diseases. Different types of morbidity dynamics (growth, undulatory pattern, and
      relative stability) form depending on the pathogenetic potential of environmental
      factors and adaptive compensatory capacities of the body.

PMID- 15141631
TI  - [Hygienic aspects of urinary system developing pathology in children (review)].
AB  - The paper deals with the impact of environmental factors of industrial cities and
      towns on children's health. Particular emphasis is laid on urinary tract
      pathology since the kidney is a xenobiotically exposed target organ. The main
      criteria for a risk of environment-induced diseases are ambient air pollution,
      low drinking water quality, soil heavy metal pollution, etc. The review covers
      the pathogenetic mechanisms and clinical features of the manifestation of renal
      diseases in children living in the regions with different heavy metal-loaded
      environment.

PMID- 15141633
TI  - [The influence of socioeconomic factors on health status and causes of mortality
      among the population].
AB  - The paper presents the results of an analysis of the relationship of a number of
      disorders and causes of death in the population to some socioeconomic factors in
      a Russian large industrial town. The relationship was analyzed for a time (8
      years) and in space (8 areas of the town). The socioeconomic situation of
      intraurban areas was integrally assessed by 16 indices. Its relationship to
      diseases and death was also studied. The findings suggest that relationships
      really exist between these phenomena.

PMID- 15141634
TI  - [Evaluation of health status in an individual].
AB  - The paper substantiates the methodology and methods of assessing the level of
      somatic health by direct indices, presents data on its informative values, and
      describes new health phenomena obtained from population surveys.

PMID- 15141635
TI  - [Assessment and promotion of individual health].

PMID- 15141636
TI  - [A systemic concept of individual health status from the standpoint of practical
      medicine. Part I. Theoretical aspects].
AB  - The paper presents the system concept of individual health in the context of
      practical medicine, which includes the definition of this widely use, the system
      forming of its understanding in the physician-patient system, the phasic pattern
      of individual health as transient prenosological and postnosological entities,
      the traditional quantitatively diagnostic and integrally quantitative principles
      in the evaluation of the level of individual health. By using these principles
      and taking into account specialization in the state public health care, the
      authors provide evidence for that it is expedient to identify the mental,
      physical, physiological, biochemical, clinical, and somatic status of a patient.
      The phasic pattern of individual health substantiates the concept of
      prenosological staging of the development of chronic diseases of specific and
      nonspecific genesis and the expediency of identifying primary and secondary
      chronic diseases of any etiology. In the authors' opinion, it is expedient to
      consider prenosological diagnosis, its categorical and terminological aspects,
      differential diagnosis, treatment, prevention, and rehabilitation of patients
      with prenosological conditions to be the general trend of scientific-and
      practical developments in the area of individual health. Methodologically, it is
      necessary to use of the entire store of methods of integrative and occupational
      medicine, particularly in the field of etiological diagnosis by risk and anti
      risk factors, of those of functional diagnosis using exercise tests and of
      clinical diagnosis of prenosological entities.

PMID- 15141637
TI  - [The use of remote probing methods to evaluate ambient air pollution].
AB  - The results of field measurements made at four stationary atmosphere observation
      posts located within the dwelling area of a large industrial town and remote
      probing data obtained from a LANDSAT satellite having an ETM sensor (Enhanced
      Thematic Mapper) and from a Terra satellite having ASTER sensory techniques were
      comparatively characterized. Based on the developed signatures (measurement
      standards), the authors drew up technogenic ambient air pollution maps by
      principal components. The findings and the data obtained by using other
      technologies, such as simulation of the diffusion of pollutants in the atmosphere
      by the maximum single and mean annual concentrations; assessment of the risk to
      human health, permitted a comprehensive assessment of the situation and were used
      to develop managerial decisions aimed at stabilizing the environmental sanitary
      situation in the region under study.

PMID- 15141638
TI  - [Gas chromatographic isolation of chloropicrin in drinking water].
AB  - Gas chromatographic method has been developed to identify chloropicrin in the
      drinking water, which is based on its separation from water by statistic gas
      extraction and on the analysis of equilibrium vapor phase on a capillary column
      with electron-capture and nitrogen-phosphorus detectors connected in series. The
      method allows chloropicrin to be detected at the level of 5 mg/dm3 with a total
      measurement error of +/- 10% at a confidence probability of 0.95. The paper shows
      that the sensitivity of identification can be significantly increased.

PMID- 15141639
TI  - [Comprehensive evaluation of endogenous intoxication in terms of toxicouria in
      hygienic studies].

PMID- 15141640
TI  - [The use of rates of emergency care referral as early signs of ecological
      illness].

PMID- 15141641
TI  - [Remembering Vladimir Aleksandrovich Riazanov, academician of the USSR Academy of
      Medical Sciences].

PMID- 15141642
TI  - More surgeons do minimally invasive heart surgery.

PMID- 15141643
TI  - How hospitals respond to cardiac care turmoil.

PMID- 15141644
TI  - [Three patients with gynaecomastia].
AB  - In three patients gynaecomastia was diagnosed: a 22-year-old man with concomitant
      thyrotoxicosis due to an extensively metastasized extragonadal choriocarcinoma, a
      53-year-old man with hypogonadism due to Klinefelter's syndrome that was
      biochemically obscured due to medications leading to elevated prolactin levels,
      and a 62-year-old man with acromegaly and secondary hypogonadism due to a mixed
      prolactin and growth hormone secreting pituitary adenoma. Gynaecomastia calls for
      thorough evaluation.

PMID- 15141645
TI  - [The hidden treasure-chests of the regional cancer registries].
AB  - For physicians and patients, knowledge of the treatment results of individual
      hospitals is of great importance as it is known that hospitals with more
      experience perform better. Oncological characteristics of cancer patients in the
      Netherlands are collected by the nine Comprehensive Cancer Centres. The data are
      available from each affiliated hospital but remain anonymous. A plea is made for
      more transparency by requiring that the Comprehensive Cancer Centers place their
      data in the public domain.

PMID- 15141646
TI  - [Expression of the cystic fibrosis gene in the lungs].
AB  - Cystic fibrosis (CF) is one of the most common hereditary diseases with a
      potentially lethal outcome. CF is caused by mutations in a gene on chromosome 7
      that encodes for a polypeptide called 'cystic fibrosis transmembrane conductance
      regulator' (CFTR). Pulmonary complications in CF are a direct consequence of a
      fault in the production or function of CFTR. The consequences of these faults are
      a change in the viscosity and volume of the air-surface liquid in the airways and
      possible malfunctioning of the immunological defence system. The result is stasis
      of mucus and obstruction of the smaller airways. Secondary to this process, a
      (chronic) infection with an uncontrolled inflammatory response, leads to
      destruction of lung tissue and a reduction in lung function. Mutations in CFTR
      can be classified in five types, which reflect the level of production or the
      function of CFTR. This classification permits discrimination between mild and
      severe mutations. The clinical image and the course of CF are often related to
      the combination of mutations present. This may explain, in part, why some CF
      patients are diagnosed at a later age with a normal sweat test and a clinical
      image that is predominantly limited to respiratory symptoms.

PMID- 15141647
TI  - [Prevention of cardiovascular complications after a stroke or TIA: hypotensive
      and hypocholesterolemic therapy].
AB  - In patients who have recently had a TIA or stroke, the risk of new serious
      cardiovascular disease is decreased by the pharmacological reduction of the serum
      cholesterol level and blood pressure; this has been convincingly demonstrated by
      randomised clinical trials. There is sufficient evidence that cholesterol
      lowering treatment is effective in patients with a TIA or cerebral infarction who
      have a total cholesterol > or = 3.5 mmol/l. The results from a trial in patients
      with only a TIA or a minor stroke will have to answer the question whether
      cholesterol-lowering treatment will be effective in patients > 80 years, and
      whether higher dosages of simvastatin will be more effective in these patients.
      Antihypertensive therapy is effective in preventing recurrent stroke and
      myocardial infarction in patients with a recent stroke or TIA. It is obvious that
      the treatment should be started with a diuretic and that a second agent should be
      added if necessary. On epidemiological grounds, vigorous treatment is also
      justified in patients with a normal or mildly elevated blood pressure; caution
      and a custom-tailored approach are essential, however, in each individual
      patient.

PMID- 15141648
TI  - [Diagnostic image (186) A man with abdominal pain in the left upper quadrant.
      Acute appendicitis with malrotation of the colon].
AB  - A 54-year-old man presented with abdominal pain in the left upper quadrant due to
      acute appendicitis with a malrotation of the colon.

PMID- 15141649
TI  - [From gene to disease; Krabbe disease and galactosylceramidase deficiency].
AB  - Krabbe disease is a devastating lysosomal storage disease with autosomal
      recessive inheritance. Early symptoms of leukodystrophy, such as irritability and
      hypertonicity, appear at 3 to 6 months of age, but progress rapidly to severe
      mental and motor deterioration and death in the second year. The disease is
      caused by the deficiency of the lysosomal enzyme galactosylceramidase, which is
      in turn caused by mutations in the GALC gene. The incidence of the infantile form
      of the disease in the Netherlands is estimated at 1.3 per 100,000 births; 50% of
      the patients' alleles show the large 30-kb deletion. Early diagnosis by enzyme
      assay in leukocytes or skin fibroblasts permits timely genetic counselling and
      prenatal diagnosis, which is reliably made by enzyme or mutation analysis in the
      chorionic villi.

PMID- 15141650
TI  - [The risk of cancer in inhabitants of Weurt, the Netherlands].
AB  - OBJECTIVE: To analyze the risk of cancer in the population of Weurt, a village
      near Nijmegen, the Netherlands, using long-term data (13 years). DESIGN: Cluster
      analysis. METHOD: Anonymous data on newly diagnosed cases of cancer in the years
      1989-2001 were obtained from the regional cancer registry. The region had about 1
      million inhabitants and 263 postal code areas. The Dutch Central Statistical
      Office (Statistics Netherlands) provided age- and sex-specific population data
      for each postal code area. Ratios of observed and expected numbers of cancer
      cases were calculated (uncorrected standardized mortality ratio; SMR). A Bayesian
      analysis with a random effects model with spatial correlation was used to adjust
      the SMRs for cancer incidence in neighbouring postal code areas. RESULTS: In the
      years 1989-2001, a total number of 167 cases of cancer (97 in males and 70 in
      females) were diagnosed in Weurt. The number of cancers in the entire area was
      58,126. In Weurt the adjusted SMR for all cancers was 1.18 (95% CI: 0.95-1.44) in
      males and 1.10 (95% CI: 0.86-1.39) in females. For lung cancer the adjusted SMR
      was 1.35 (95% CI: 0.88-1.94) in males and 1.00 (95% CI: 0.29-2.13) in females.
      None of the other types of cancer showed a statistically significant increase in
      incidence in Weurt. CONCLUSIONS: Although based on relatively small numbers of
      diagnosed cancers, these results are not suggestive of a real cancer cluster in
      Weurt. Lung cancer incidence was slightly increased in males and not in females,
      which may indicate that chance, lifestyle or occupational factors were more
      obvious causes than environmental factors. In general, it is advised to be
      reluctant to perform cluster analyses. Such analyses may only be valuable if
      specific hypotheses regarding causes of specific types of cancer are present.

PMID- 15141651
TI  - [Community-acquired pneumonia: pathogens and course in patients admitted to a
      general hospital].
AB  - OBJECTIVE: To determine prognostic factors and the significance of (non-invasive)
      microbiological tests for the clinical course of patients admitted to one general
      hospital with community-acquired pneumonia (CAP). DESIGN: Prospective
      observational study. METHOD: Patients admitted to one location of a general
      hospital with symptoms of CAP during the period January 1998-December 1999 were
      included. Data from the anamnesis, physical examination and laboratory tests were
      recorded and samples were taken for diagnosis of the possible pathogens. Cultures
      were made of sputum and blood, serum and sputum were examined for infection with
      viral and atypical microorganisms, and the urine was screened for Streptococcus
      pneumoniae and Legionella antigens. RESULTS: Of the 157 patients studied, 28
      (18%) died as a direct result of CAP. In a stepwise multivariate analysis, age >
      or = 65 years, increased serum-creatinine levels and hypercapnia were independent
      predictors of mortality. Streptococcus pneumoniae and Haemophilus influenzae were
      detected 53 and 19 times, respectively, and were the bacterial pathogens most
      frequently found. Among the nonbacterial pathogens, Mycoplasma pneumoniae was
      found 37 times and serologic tests for influenza A or B virus were positive in 34
      cases. In 62 patients (39%), extensive microbiological tests revealed signs of a
      combined infection and in 20 patients (13%) no microorganism could be detected.
      An elevated serum-procalcitonin level was associated with bacterial infections.
      As a consequence of their retrospective nature, the results of the extensive
      serological tests did not contribute to reaching a diagnosis in daily clinical
      practice. In comparison with the literature, there was a markedly high number of
      subclinical or atypical infections with Legionella (8%) and Bordetella (18%) and
      a high incidence of viral and atypical microorganisms as the cause of CAP.

PMID- 15141652
TI  - [A cavernous haemangioma of the colon as the cause of rectal bleeding in
      childhood].
AB  - A 13-year-old girl presented with rectal bleeding, abdominal pain and a palpable
      mass in the lower right abdomen. The history mentioned a chronic anaemia since
      she was 2 years old. Further examination did not give any indications for
      inflammation as etiological factor and showed a thickening of (apparently) the
      small intestine. A laparotomy was performed, since the age and presentation made
      a malignant lymphoma a probable diagnosis. The combination of chronic anaemia and
      rectal bleeding also suggested a benign vascular malformation. A large cavernous
      haemangioma of the transverse colon was found. This was resected and the patient
      fully recovered. Although a haemangioma of the colon is rare, it is important to
      keep this possibility in mind in the case of rectal bleeding in childhood,
      especially when other causes of rectal bleeding are excluded. Usually
      haemangiomas show spontaneous regression, but this is rare in intestinal
      haemangiomas. Surgical resection is the therapy of choice in the case of a
      solitary haemangioma.

PMID- 15141653
TI  - [Recognition and treatment of gamma hydroxybutyric acid poisoning].
AB  - The number of cases of gamma-hydroxybutyric acid (GHB) poisoning is increasing
      rapidly. The substance is becoming more and more popular as a party drug, while
      the users are often unaware of the potential dangers of GHB abuse. If a GHB
      overdose is treated properly and on time, the patient generally recovers
      completely within 6 hours. Preventing aspiration and the timely initiation of
      artificial respiration are particularly important.

PMID- 15141654
TI  - [The practice guideline 'Acute cough' from the Dutch College of General
      Practitioners; a response from the perspective of pulmonology and family
      practice].

PMID- 15141655
TI  - [Giant diverticulum of the sigmoid].

PMID- 15141656
TI  - [Diabetic nephropathy: the role of blood pressure and extra-cellular volume in
      its pathogenesis and treatment].

PMID- 15141657
TI  - [Part-time medical specialist training; experiences with job-sharing for trainee
      internists].

PMID- 15141658
TI  - [Part-time medical specialist training; experiences with job-sharing for trainee
      internists].

PMID- 15141659
TI  - [The Dutch Institute for Health Care Improvement (CBO) guideline for the
      diagnosis and treatment of aspecific acute and chronic low back complaints].

PMID- 15141660
TI  - [The Dutch Institute for Health Care Improvement (CBO) guideline for the
      diagnosis and treatment of aspecific acute and chronic low back complaints].

PMID- 15141661
TI  - [The Dutch Institute for Health Care Improvement (CBO) guideline for the
      diagnosis and treatment of aspecific acute and chronic low back complaints].

PMID- 15141662
TI  - [Clinical case of the month. Superficial angiomyxoma].
AB  - Some cutaneous neoplasms are seemingly harmless, but they may prove to be
      problematic due to their propensity to invade or to recur. We present 2 cases of
      superficial angiomyxoma.

PMID- 15141664
TI  - Estimating the cost of caring for California's uninsured.

PMID- 15141663
TI  - [Special aspects of implant-associated infection in orthopedic surgery. From the
      pathophysiology to custom-tailored prevention strategies].
AB  - One of the most important risk factors in orthopedic surgery is implant
      associated infection. Adhesion and colonization mediated implant infections are
      extremely resistant to antibiotics and host defences and frequently persist until
      the biomaterial or foreign body is removed, which is standard therapy. Tissue
      damage caused by surgery and foreign body implantation increases the
      susceptibility to infections, activates host defences and stimulates the
      generation of inflammatory mediators including radicals that are further
      aggravated by bacterial activity and toxins. Nearly one third of implant-related
      infections can be prevented by strictly following established infection control
      guidelines. However, a significant number of implant-associated infections
      remains. The escape of bacteria from host defence and antibiotic therapy makes
      the development of infection-resistant materials as anti-microbial drug delivery
      systems feasible. This concept consists of the sustained delivery of
      antimicrobial drugs into the local microenvironment of implants avoiding systemic
      side effects exceeding usual systemic concentrations by magnitudes of order.

PMID- 15141667
TI  - [Proceedings of the Fifth Annual Congress of the Croatian Rheumatology Society
      held in Sibenik-Solaris, 17-19 October 2003].

PMID- 15141665
TI  - [Pathophysiology of posttraumatic osteitis].
AB  - Over the last few decades, significant reduction of post-traumatic infections
      could be attained by establishing novel surgical techniques and tactics, by
      adapting surgical decisions to the risk of infection, by employing
      chemotherapeutic agents, and by developing new implants. Here a novel
      understanding of the pathophysiologic mechanisms of post-traumatic and
      postoperative osteomyelitis were directive. Nevertheless, post-traumatic
      infections later cause significant physical and economic sequelae. This article
      sums up the fundamental pathophysiological mechanisms of post-traumatic
      infection. New ideas about post-traumatic prevention and therapy of osteomyelitis
      are discussed.

PMID- 15141666
TI  - [Hygiene between tradition and implementation].
AB  - The basis of evidence for hygiene rules implemented in hospitals is traditionally
      small. This is not only because there is little theoretical knowledge on the
      reciprocal influence between a single hygienic mistake/a single microbial input
      and the manifestation of a nosocomial infection. There are also not enough
      clinical studies, especially on complex hygiene questions, to determine whether
      special measures (e.g., septic rooms)can compensate for deficits in hygiene
      practice. Furthermore, it would be necessary to designate security buffers
      distinctly. In-house traditions are able to stabilize hygienic behavior in an
      excellent manner. They should be fostered and not disparaged as myths.
      Discussions of experts should not be conducted in public; that is disastrous for
      the everyday work of physicians in hospitals.

PMID- 15141668
TI  - [Antibiotic prophylaxis in cases of closed fractures and prostheses].
AB  - Antibiotic prophylaxis can be administered systemically or locally when bone
      cement is used for the implantation of prosthesis. In closed fracture surgery
      parenteral broad spectrum antibiotics are advised with 1 dose (in case of a long
      halflife) or for at least 12 hours when an antibiotic with a shorter half life is
      used. With such a prophylaxis a reduction of the infection rate to about 3% can
      be achieved, and also an important reduction of the postoperative nosocomial
      infections. Such a prophylaxis is highly cost effective. In primary prosthesis
      implantation, a 24 hours prophylaxis is needed. The use of antibiotic loaded bone
      cement, used as prophylaxis in primary prostheses is effective too, and this kind
      of cement should be used in combination with systemic antibiotics. In prosthesis
      an infection rate of 0.2% should be achieved.

PMID- 15141669
TI  - [From severe acute respiratory syndrome crisis to acquired immunodeficiency
      syndrome crisis].

PMID- 15141670
TI  - [Timely actions on childhood obesity].

PMID- 15141671
TI  - [Principles of surgical therapy concepts for postoperative and chronic
      osteomyelitis].
AB  - Infection of the bone is one of the most serious complications in the field of
      orthopedic and trauma orthopedic surgery. Sufficient treatment protocols not only
      contain complex surgical procedures but also sophisticated diagnostic tools,
      proper use of antibiotics, and intensive physical therapy right from the
      beginning. Even in light of these advanced treatment protocols, which have great
      impact on both patients and health care systems, persisting infection and
      residual functional deficits of the extremities are not rare. In cases of early
      (acute) infection, the main objective is to avoid chronification by diligent
      surgical interventions. The surgical principle is the meticulous debridement and
      lavage of the situs. Revision of only the epifascial layers is as inadequate as
      the simple reopening of the wound without excision of the whole wound including
      all tissue layers. In cases of chronic soft tissue and bone infection, radical
      debridement of all infected and scar tissue is also the basic requirement of
      treatment. Reconstruction of the soft tissue envelope is done by local or free
      flap surgery. Because of they are better resistant to infection,
      musculo(cutaneous)flaps are preferred. Bony reconstruction is done by autologous
      cancellous bone grafting (partial defects), segment transport (full thickness
      defects), or freely transplanted vascularized bone grafts (large partial
      defects). Both soft tissue and osseous reconstruction take a relatively long
      period of time requiring several operations and periods of hospitalization. These
      have to be discussed and explained to the patients extensively. If the required
      amount of resection and the capability of reconstruction do not coincide, the
      surgeon and the patient have to decide whether restoration of function without
      definitive infection care, symptomatic infection therapy, or amputation is the
      most proper treatment option according to the patient's everyday needs and
      lifestyle. Because each treatment protocol is a composition of orthopedic trauma
      surgeons, plastic surgeons, radiologists, microbiologists, and physical
      therapists, reliable cooperation and communication is essential.

PMID- 15141672
TI  - [Pro- and supination impairments due to torsional deformities of the radial
      diaphysis before and after ulna osteotomy].
AB  - The aim of this experimental study was to measure the exact influence of
      torsional deformities at the middle third of the radial shaft before and after
      osteotomy of the ulnar shaft on the rotation of the forearm. Intact and fresh
      cadaver specimens were fixed in a newly developed apparatus that allowed free
      pronation and supination. A ring fixator was applied to the radial shaft with K
      wires that allowed torsional deformities to be stabilized in steps of 10 degrees.
      The middle of the radial shaft was osteotomized via a small soft tissue window
      leaving the other soft tissues including the interosseous membrane intact.
      Supination and pronation were measured using a goniometer in a standardized
      fashion. The mean supination value before osteotomy of the radius was 71.6
      degrees [standard deviation (SD)15.2 degrees], the mean pronation value was 64.5
      degrees (SD 12.4 degrees). Radial osteotomy caused no significant difference in
      the range of motion prior to creation of torsional deformities. Supination
      torsional deformities greater than 30 degrees showed a significant loss of
      pronation and pronation torsional deformities greater than 30 degrees resulted in
      a significant loss of supination in 14 fresh cadavers, respectively. The amount
      of mean rotational loss was approximately the same in the respective pronation
      and supination torsional deformities. In the next step the influence of an ulna
      osteotomy on the range of motion was evaluated in different torsional
      deformities. In the four cadavers measured, there was an increase of the range of
      motion in the direction of the torsional deformity. These values were not
      significant when compared to values before ulna osteotomy, but there were
      significant changes to the non deformity (p=0.004 for pronation, p=0.003 for
      supination). Impairment of range of motion in the opposite direction of the
      deformity showed a similar appearance as values before ulna osteotomy. Again,
      there were significant changes to the non deformity (p=0.003 for pronation,
      p=0.005 for supination).

PMID- 15141673
TI  - The roller coaster of antioxidant therapy.

PMID- 15141674
TI  - Hunting and fishing.

PMID- 15141675
TI  - Antidiarrheal drug products for over-the-counter human use; amendment of final
      monograph. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule amending the final
      monograph (FM) for over-the-counter (OTC) antidiarrheal drug products to include
      relief of travelers' diarrhea as an indication for products containing bismuth
      subsalicylate. Travelers' diarrhea occurs in travelers and is most commonly
      caused by an infectious agent. This final rule is part of FDA's ongoing review of
      OTC drug products.

PMID- 15141676
TI  - Dental devices; reclassification of root-form endosseous dental implants and
      endosseous dental implant abutments. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying root-form endosseous
      dental implants and endosseous dental implant abutments from class III to class
      II (special controls). Root-form endosseous dental implants are intended to be
      surgically placed in the bone of the upper or lower jaw arches to provide support
      for prosthetic devices, such as artificial teeth, in order to restore the
      patient's chewing function. Endosseous dental implant abutments are separate
      components that are attached to the dental implant and intended to aid in
      prosthetic rehabilitation. FDA is reclassifying these devices on its own
      initiative on the basis of new information. Elsewhere in this issue of the
      Federal Register, FDA is announcing the availability of the guidance document
      that will serve as the special control for these devices. FDA is taking this
      action under the Federal Food, Drug, and Cosmetic Act (the act), as amended by
      the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical
      Devices Act of 1990, the Food and Drug Administration Modernization Act of 1997,
      and the Medical Device User Fee and Modernization Act of 2002.

PMID- 15141677
TI  - World War I maxillofacial fracture splints.

PMID- 15141678
TI  - Oral surgery in patients taking anticoagulant therapy.

PMID- 15141680
TI  - Geography, race, and health.

PMID- 15141681
TI  - The effect of Medicaid HMOs on spending and health outcomes.

PMID- 15141679
TI  - Cigarette taxes and prenatal and maternal smoking.

PMID- 15141682
TI  - The effect of new drugs on longevity.

PMID- 15141683
TI  - Health insurance subsidies, coverage, and costs.

PMID- 15141684
TI  - The market for stand-alone prescription drug insurance.

PMID- 15141685
TI  - How health declines with age.

PMID- 15141686
TI  - How the aging process changed during the 20th century.

PMID- 15141687
TI  - How hospitals respond to changes in Medicare reimbursements.

PMID- 15141688
TI  - The effect of welfare reform on the insurance status and health of low-income
      families.

PMID- 15141689
TI  - Errors in the Social Security Disability award process.

PMID- 15141690
TI  - Does enrolling in Medicare HMOs affect mortality?

PMID- 15141691
TI  - Do longer maternity leaves affect maternal health?

PMID- 15141692
TI  - The digital transformation of health care.

PMID- 15141693
TI  - Members only for EU health care.

PMID- 15141694
TI  - Microbicides strike an upbeat note.

PMID- 15141695
TI  - New human coronavirus isolated.

PMID- 15141696
TI  - Slow progress worries Stop TB Partnership.

PMID- 15141698
TI  - FDA plans warning labels for condoms.

PMID- 15141697
TI  - Is chronic rhinosinusitus a fungal problem?

PMID- 15141699
TI  - USA establishes advisory board for "dual use" research.

PMID- 15141701
TI  - Egypt conquers lymphatic filariasis.

PMID- 15141702
TI  - Mechanical cardiac support system for patients with postcardiotomy cardiogenic
      shock: analysis of risk factors for survival.
AB  - OBJECTIVE: Mechanical cardiac support system (MCSS) has been used for adult
      patients in postcardiotomy cardiogenic shock and has been shown to provide
      excellent oxygenation and hemodynamic support. However, MCSS has a number of
      disadvantages that include high incidence rate of complications (e.g. stroke,
      bleeding) and limited duration of sufficient support. The objective of this study
      is to identify perioperative and postoperative factors for survival in patients
      having MCSS. METHODS: From January 1991 to April 2001, MCSS has been applied to
      22 adult patients in postcardiotomy cardiogenic shock. These patients' charts
      were retrospectively reviewed. RESULTS: Of 22 patients, 9 patients (41%) were
      successfully weaned, and 6 (27%) were hospital survivors. The duration of assist
      ranged from 21 to 211 hours (median 66 hours). In 7 (78%) out of 9 patients who
      could be weaned from MCSS, MCSS were required for less than 3 days. Major
      complications were reexploration for bleeding (18%), leg ischemia (45%), renal
      dysfunction (77%), liver dysfunction (59%), infection (31.8%), hypoxia due to
      lung dysfunction (36%) and cerebral dysfunction (41%). pH, base excess, HCO3-,
      urine output, transfused platelets at first 24 hours of MCSS and preoperative
      body surface area were significant predictors for survival. CONCLUSION: The
      indices of insufficient hemodynamic support such as progression of acidosis or
      poor urine output are significant predictors for early death. Early conversion
      from MCSS to long-term assist device, such as left ventricular assist device,
      should be considered when these factors are associated with poor cardiac
      recovery.

PMID- 15141703
TI  - Allowable warm ischemic time to tracheal extraction for allotransplantation of
      cryopreserved trachea.
AB  - OBJECTIVE: The allowable warm ischemic time from circulatory arrest to tracheal
      extraction for allotransplantation of cryopreserved tracheal grafts from
      cadaveric donors was examined in adult mongrel dogs. SUBJECTS AND METHODS: The
      animals were divided into 4 groups (n = 28) according to the warm ischemic time
      of less than 1 hour, 3 hours, 6 hours, and 12 hours, after transplantation, and
      comparisons were made. The grafts were cryopreserved for at least 2 months and
      were evaluated by extraction from the recipients generally 2 months after
      transplantation. RESULTS: All the grafts with a warm ischemic time of less than 1
      hour were viable and did not show stenosis. This group did not differ
      significantly from the groups with a warm ischemic time of 3 and 6 hours in terms
      of viability. However, all of the grafts with a warm ischemic time of 12 hours
      showed stenosis, and there was a significantly lower viability rate. Histological
      examination of the grafts showed that warm ischemia caused necrosis of the
      tracheal cartilage. CONCLUSION: Based on these results, it was concluded that 6
      hours was the maximum allowable warm ischemic time for cryopreserved tracheal
      transplantation, and that necrosis of the tracheal cartilage due to warm ischemia
      reduced the viability of the grafts.

PMID- 15141704
TI  - Effect of biventricular pacing therapy in patients with dilated cardiomyopathy
      with severe congestive heart failure.
AB  - OBJECTIVES: Biventricular pacing (BVP) therapy has recently emerged as an
      effective treatment for patients with moderate to severe congestive heart failure
      (CHF) and ventricular asynchrony all over the world. However, this therapy is not
      yet available in Japan. We evaluated the effects of BVP in patients with severe
      CHF due to dilated cardiomyopathy (DCM). SUBJECTS: Four patients with medically
      refractory severe CHF due to DCM in New York Heart Association functional class
      III or IV heart failure underwent BVP therapy. We combined the implantation of
      the left ventricular (LV) epicardial lead via small thoracotomy following right
      atrial and ventricular intravenous leads under general anesthesia. We evaluated
      to determine whether improvements of ventricular function, ventricular size,
      mitral regurgitation, functional status, frequency of hospitalization, and
      quality of life were associated with BVP therapy. RESULTS: BVP improved LV
      systolic function, decreased LV size and mitral regurgitation, and shortened
      prolonged QRS interval. The patients' symptoms, exercise tolerance, frequency of
      hospitalization, and quality of life were also dramatically improved by BVP.
      Furthermore, combination of BVP and oral administration of amiodarone
      significantly prevented recurrence of ventricular tachycardia and paroxysmal
      atrial fibrillation, and maintained sinus rhythm for a long period. CONCLUSIONS:
      In view of these findings, BVP therapy may contribute to the development of new
      therapeutic method for patients with severe CHF due to DCM.

PMID- 15141705
TI  - Superior sulcus lung cancer invading the ribs and brachial plexus successfully
      resected by modified trap-door thoracotomy after induction chemoradiotherapy.
AB  - We report on a 49-year-old male patient presented with right superior sulcus lung
      adenocarcinoma, which had invaded the first and second ribs and brachial plexus.
      He underwent concurrent chemoradiotherapy, which resulted in a partial response.
      The tumor was resected along with the first and second ribs without difficulty
      via a modified trap-door thoracotomy. The brachial plexus was preserved, and the
      surgical margin was microscopically negative for cancer due to the effect of the
      neoadjuvant chemoradiotherapy which degenerated most of the tumor into scar
      tissue. We conclude that modified trap-door thoracotomy is a good approach for
      resection of superior sulcus lung cancer invasive to the first and second ribs
      and brachial plexus. Neoadjuvant chemoradiotherapy is also necessary to achieve a
      negative surgical margin.

PMID- 15141706
TI  - When should pulmonary artery angioplasty be performed for Fontan candidates with
      pulmonary coarctation? Two cases of pulmonary artery angioplasty with the Blalock
      Taussig shunt on pump in neonates.
AB  - We performed concomitant pulmonary artery angioplasty and the Blalock-Taussig
      shunt under median sternotomy and cardiopulmonary bypass at the neonatal stage in
      Fontan candidates with pulmonary coarctation to obtain optimum pulmonary
      circulation. This surgical strategy realized appropriate early growth of the
      pulmonary artery necessary for the Fontan operation.

PMID- 15141707
TI  - Incidental partial anomalous pulmonary venous connection in left lung cancer.
AB  - We present the case of a 79-year-old woman with partial anomalous pulmonary
      venous connection (PAPVC), discovered incidentally during upper left division
      segmentectomy for primary lung cancer. The left superior pulmonary vein
      originated from the hilum of the upper left lobe and flowed into the left
      brachiocephalic vein. The left inferior pulmonary vein was connected normally,
      and neither atrial septal defect nor other anomalous condition was present. Upper
      left lobectomy with ligation of the anomalous connected vein was performed, as
      the lingual segment was anatomically difficult to retain. Although this type of
      PAPVC is extremely rare, it is advisable to exercise caution when performing lung
      resection with the potential for PAPVC in mind.

PMID- 15141708
TI  - Coronary artery bypass grafting with absent right superior vena cava in
      visceroatrial situs solitus.
AB  - We report on a 63-year-old man with an absence of right superior vena cava in
      visceroatrial situs solitus who underwent coronary artery bypass grafting.
      Preoperative echocardiography showed a dilated coronary sinus, and venography
      confirmed an absent right and a persistent left superior vena cava.
      Perioperatively, placement of a pulmonary artery catheter, site of venous
      cannulation, and management of associated rhythm abnormalities were of great
      concern. The assessment of the right superior vena cava is advisable in carrying
      out the surgical procedure without any difficulties related to this anomaly when
      the persistent left superior vena cava is suspected.

PMID- 15141709
TI  - Surgical treatment for intrathoracic aneurysm of the innominate artery in an 83
      year-old asymptomatic woman.
AB  - Aneurysm of the innominate artery is uncommon compared with other peripheral
      aneurysms, and holds the potential for rupture, embolization, or thrombosis as
      well as various complications caused by compression to the adjacent structures.
      The most effective treatment for this condition is surgical resection, but the
      earlier reports described high mortality rates. We report the case of an 83-year
      old asymptomatic woman with an aneurysm in the innominate artery, which was
      successfully resected and repaired with the use of modern surgical techniques of
      hypothermic circulatory arrest and selective cerebral perfusion. Aggressive
      surgical intervention should be employed despite the fact that a patients is
      asymptomatic.

PMID- 15141710
TI  - Intermittent circulatory arrest for repairing postoperative mycotic
      pseudoaneurysm in the ascending aorta.
AB  - Postoperative mycotic pseudoaneurysm in the ascending aorta associated with
      mediastinitis is one of the most serious complications after cardiovascular
      surgery. Circulatory arrest is usually needed for repairing this lesion; it is
      likely that the procedure needs unpredictably prolonged arrest time due to
      uncontrollable bleeding or serious adhesion. With this reason we employed
      intermittent circulatory arrest instead. The purpose of this paper is to describe
      2 cases which demonstrated the method of intermittent circulatory arrest for
      repairing postoperative mycotic pseudoaneurysm in the ascending aorta.

PMID- 15141711
TI  - Fatal ischemia of bowel and rectus abdominal muscle after off pump coronary
      artery bypass grafting in a dialysis patient.
AB  - We have experienced a case which developed mesenteric ischemia followed by
      necrosis of the rectus abdominal muscle after off pump coronary artery bypass
      grafting (OPCAB). A 62-year-old man with a history of long-term hemodialysis was
      diagnosed with left main trunk disease. He underwent triple OPCAB uneventfully.
      No inotropic agents were needed perioperatively. He underwent normal hemodialysis
      on the first postoperative day, and then complained of severe abdominal pain with
      progressive metabolic acidosis. A 170 cm length of the ileocecal segment fell
      into necrosis and was excised and an ileostomy was constructed in an emergency
      setting. He developed another abdominal pain 6 days after the second operation.
      An additional surgery confirmed necrosis of the right rectus abdominal muscle
      complicated with a significant infection. He developed mediastinitis and died of
      multi-system organ failure 37 days after OPCAB. The mechanism of this serious
      complication is discussed.

PMID- 15141712
TI  - Intravascular ultrasound imaging for detection of pseudoaneurysm with
      aortobronchopulmonary fistula after graft replacement of descending aorta.
AB  - A 63-year-old man had undergone graft replacement of the descending aorta due to
      dissection of aortic aneurysm nine years before and closure of an
      aortobronchopulmonary fistula two years before. He was admitted to our hospital
      because of massive hemoptysis. Angiography and chest computed tomography (CT)
      revealed a pseudoaneurysm on the proximal end caused by graft detachment.
      Intravascular ultrasound clearly revealed half round detachment on both ends of
      the graft. Replacement of the ascending, arch and distal aorta including the
      graft was performed, and the patient's postoperative course has been
      satisfactory. We have concluded that intravascular ultrasound is a useful method
      for detecting pseudoaneurysm after graft replacement which is not evident on
      cineangiography, CT or distal subtraction angiography.

PMID- 15141713
TI  - Sternal resection for metastasis from thyroid carcinoma and reconstruction with
      the sandwiched Marlex and stainless steel mesh.
AB  - A case of 69-year-old woman with a solitary sternal bone metastasis from thyroid
      carcinoma undergoing surgical therapy was reported here. On admission, most part
      of the body of the sternum was destroyed by tumor. Subtotal sternectomy was
      performed and a part of the major pectoral muscles adherent to the sternal tumor
      was also resected. The chest wall defect was reconstructed with a sandwiched
      Marlex and stainless steel mesh. Pathological examination of the resected
      specimen revealed metastatic papillary carcinoma of the thyroid. Her
      postoperative course was uneventful. The reconstruction with Marlex and stainless
      steel mesh seemed to be an appropriate procedure to prevent paradoxical movement
      of the thorax and protect the intrathoracic organs. Stainless steel mesh
      compensated for limited resiliency of Marlex mesh and remained rigid in all
      directions.

PMID- 15141714
TI  - Atrial septal defect with borderline pulmonary vascular disease: surgery and long
      term oral prostacyclin therapy for recalcitrant pulmonary hypertension.
AB  - The hemodynamic determination of operability in atrial septal defect (ASD) with
      severe pulmonary hypertension is problematic. Therefore, we perform an open lung
      biopsy prior to the corrective surgery in cases with pulmonary vascular
      resistance greater than 8 units x m2 and/or pulmonary arterial peak pressure
      greater than 70 mmHg. We present 4 cases showing occlusion of more than 70% of
      the small pulmonary arteries and arterioles by musculoelastosis, thromboembolism
      and mixed-type (musculoelastosis and plexogenic arteriopathy) which was
      considered borderline in terms of operability. After complete closure of the ASD
      and postoperative long-term oral prostacyclin (PGI2) therapy, pulmonary artery
      peak pressure decreased from 110-72 (mean 84) to 105-45 (mean 74) mmHg
      immediately after operation and 65-40 (mean 57) mmHg after PGI2 therapy. The New
      York Heart Association functional status of the patients improved from class II
      III to class I with oral PGI2 only. Our cases demonstrate that despite more than
      70% occlusion of the small pulmonary arteries and arterioles, surgery and long
      term PGI2 therapy can reduce pulmonary artery pressure and improve the quality of
      life.

PMID- 15141715
TI  - Paraganglioma of the posterior mediastinum diagnosed by immunohistochemical
      staining.
AB  - Paraganglioma of the mediastinum are rare neoplasms. To date, no definitive
      morphologic criteria exist that correlate with the clinical outcome of these
      tumors. We have encountered a case of paraganglioma in which biological behavior
      was assessed by immunohistochemical staining to determine whether supplementary
      postoperative treatment was needed. A 28-year-old man came to our hospital
      because of an abnormal shadow on a radiogram of the chest. He had no symptoms.
      Hematological findings were unremarkable. Diagnostic imaging suggested a
      neurogenic tumor. Surgical resection was performed in September, 2002. A typical
      nesting pattern (Zellballen) and positivity for chromogranin on
      immunohistochemical staining were evident, indicating neuroendocrine
      characteristics, and paraganglioma was diagnosed. Tissue specimens indicated an
      MIB-1-labeling index of 1.3% on MIB-1 staining, and a relatively well maintained
      distribution of S-100 protein-positive sustentacular cells, which were suggestive
      of a benign tumor. The patient did not receive any supplementary therapy
      postoperatively but was given careful follow-ups.

PMID- 15141717
TI  - Comparison of the effects of various periodontal rotary instruments on surface
      characteristics of root surface.
AB  - The efficacy of scaling and root planing using various periodontal rotary
      instruments was examined. Eighty extracted human teeth with a history of
      periodontal disease were divided into four groups of 20 and subjected to one of
      the following procedures: Use of 1) a Root Burnisher, 2) a Perio Planing Bur
      (both rotating instruments for contra angle handpieces), 3) a Tooth Planing Bur
      (rotating instrument for use with an air turbine), or 4) a Gracey Scaler. In each
      case, the time required for cleaning was measured. Twenty healthy extracted human
      teeth were used as untreated controls. After treatment, the surface roughness of
      10 specimens out of each group were measured using a profilometer and observed by
      scanning electron microscopy (SEM). Half of the samples were then incubated in
      dishes with a suspension of fibroblasts. After counting the number of attached
      cells, the attachment of fibroblasts was observed by SEM. The root surfaces
      treated with the rotary instruments appeared smooth and there were no significant
      differences between groups. From the SEM observations, smooth root surfaces with
      different surface textures were evident and a tight attachment of fibroblasts was
      observed. The results of this study suggest that use of rotary instruments is
      superior for periodontal scaling and root planing.

PMID- 15141716
TI  - Left atrial myxoma with severe inflammatory response.
AB  - A 59-year-old man was admitted for intermittent fever. His temperature was 38
      degrees C, white blood cell counts 19,800/mm3, C-reactive protein 17.9 mg/dL.
      Interleukin 6 (IL-6) serum level was 31.0 pg/mL. Transesophageal echocardiography
      showed a 6 x 4 cm left atrial tumor arising from the atrial septum. We strongly
      suspected that left atrial myxoma caused the fever. The tumor was excised with
      the aid of cardiopulmonary bypass. Tumor histology was typical of a cardiac
      myxoma. The serum IL-6 level decreased rapidly in postoperative two weeks (5.3
      pg/mL). In this patient, IL-6 plasma level might be used as a marker of
      recurrence.

PMID- 15141718
TI  - Differential gene induction in macrophage-like human cells by two types of
      Porphyromonas gingivalis: a microarray study.
AB  - Several studies have provided clinical evidence that FimA clonal variation may
      contribute to the periodontopathogenicity of Porphyromonas gingivalis (P.g.). We
      studied the gene expression profiling of the macrophage-like human cell line U937
      after infection of two types of P.g. (fimA type I; Pg-I and fimA type II; Pg-II)
      using microarray. Of 1088 genes examined, 394 genes were detectable.
      Bioinformatics algorithms were used to analyze the detectable genes. Hierarchical
      clustering analysis showed that gene expression patterns of Pg-II and the control
      (no infection) were grouped together. K-means clustering grouped 79 genes into Pg
      II dominance and 88 genes into Pg-I dominance. A large number of genes related to
      cell signaling, extracellular communication proteins, cell receptors (by
      ligands), protein turnover and cell adhesion receptors/proteins were grouped into
      clusters of Pg-I dominance. Our results indicate that compared with Pg-I, Pg-II
      induces a low host response as measured by its weak induction of gene expression.

PMID- 15141719
TI  - Investigation of natural head posture in different head types.
AB  - The aim of this study was to investigate natural head posture (NHP) in different
      head types. Lateral cephalograms of 99 adults (Mean age, 21.8 years +/- SD, 2.2
      yrs, range between 19 and 29 yrs) were examined. Head types were determined as
      Hyperbrachycephal, Brachycephal, Mesocephal or Dolichocephal according to the
      cephalic index. Analysis of variance and the Duncan's test were performed to
      assess inter-group differences for the parameters. The findings revealed that,
      NHP was statistically not different between the head type groups. Thus, it was
      suggested that environmental factors during growth may alter NHP, as well as
      craniofacial morphology but in a different manner (i.e. degree and direction) in
      each head type.

PMID- 15141720
TI  - Profiling of differentially expressed genes in human gingival epithelial cells
      and fibroblasts by DNA microarray.
AB  - Gingival epithelial cells and fibroblasts play important roles and have a
      harmonious relationship under normal and disease conditions, but the precise
      differences between theses cells remain unknown. To study the differences in gene
      expression between human gingival epithelial cells (HGE) and human gingival
      fibroblasts (HGF), mRNA was recovered from primary cultured cells and analyzed
      using cDNA microarray technology. The cDNA retro-transcribed from equal
      quantities of mRNA was labeled with the fluorescent dyes Cy5 and Cy3. The mixed
      probes were then hybridized with 7276 genes on the DNA microarray, after which
      fluorescence signals were scanned and further analyzed using GeneSpring software.
      Of the 7276 genes screened, 469 showed expression levels that were more than 2
      fold greater in HGE than in HGF, while 293 showed expression levels that were
      more than 2-fold greater in HGF than in HGE. To confirm the reliability of the
      microarray results, keratin K5 and desmocolin, and vimentin and gp130, which
      showed higher mRNA levels in HGE and HGF, respectively, were selected and their
      mRNA levels were further analyzed by RT-PCR. The results of RT-PCR correlated
      well with those of microarray analysis. The present findings using a DNA
      microarray to detect differences in the gene expression profiles of HGE and HGF
      may be beneficial for genetic diagnosis of periodontal tissue metabolism and
      periodontal diseases.

PMID- 15141721
TI  - A comparative evaluation of the clinical effects of systemic and local
      doxycycline in the treatment of chronic periodontitis.
AB  - In this study, the clinical efficacies of systemic doxycycline (SD) and local
      doxycycline (LD) in the treatment of chronic periodontitis were compared. Forty
      five patients were studied in 3 main groups with 5 treatments: SD alone,
      SD+scaling-root planing (SD+SRP), LD alone, LD+SRP and SRP alone. Antibiotic
      treated patients were given doxycycline treatment alone in 1 quadrant of their
      upper jaws, and doxycycline+SRP was given in the contralateral quadrant. The
      areas included at least 4 teeth with > or = 5 mm pockets. Probing depth (PD),
      clinical attachment level, gingival index, sulcular bleeding index and plaque
      index values were recorded at baseline and the 7th week. The results were
      statistically analyzed. All of the clinical parameters were significantly reduced
      by all treatments (P < or = 0.05). The SD and LD treatments alone provided
      significant clinical healings. The significant differences among the groups were
      only in PD at the 7th week. The LD treatment provided significantly higher PD
      reduction than the SD treatment (P < or = 0.05). No significant difference was
      found between the SD+SRP and the LD+SRP treatments. There was no significant
      difference between SD+SRP and SRP alone treatment (P > 0.05). The SD group showed
      lower PD reduction than SRP group (P < or = 0.05), while no significant
      difference was found between LD and SRP treatments. The LD alone treatment seemed
      more effective than SD alone treatment on PD reduction, but no significant
      difference was found between them when combined with the SRP. LD may be more
      preferable than SD as an adjunct to mechanical treatment since LD seems more
      effective than SD on PD reduction and does not have the side effects of SD.

PMID- 15141722
TI  - The effect of basic fibroblast growth factor on cell cycle in human gingival
      fibroblasts from nifedipine responder and non-responder.
AB  - It has previously been demonstrated that gingival fibroblasts derived from
      nifedipine-reactive patients (nifedipine responders) show a greater cell
      proliferation rate than those from nifedipine non-reactive patients (nifedipine
      non-responders) in the presence of 1 microM nifedipine. The aim of the present
      study was to characterize cell cycle differences between nifedipine responder and
      non-responder fibroblast cells and determine the effect of basic fibroblast
      growth factor (bFGF) on cell cycle progression. Further, the effect of bFGF on
      cyclins A, B1, D1, E, and CDKs 1, 2, 4, 6 mRNA expression in responder and non
      responder cells was investigated. A population of nifedipine responder cells
      underwent progression to S and G2/M phases from G0/G1 phase in the presence of
      10% fetal calf serum or 10 ng/ml bFGF was greater than nifedipine non-responder
      cells. mRNA expression of cyclins A, B1, D1, E and CDKs 1, 2, 4, 6 in the
      presence of 10 ng/ml bFGF was generally greater in nifedipine responder cells
      than non-responder cells. These results indicate that nifedipine responder cells
      may be more susceptible to growth factors such as bFGF with a resultant increase
      in expression of cyclins and CDKs in responder compared with non-responder cells.

PMID- 15141723
TI  - In vitro inhibition of caries-like lesions with fluoride-releasing materials.
AB  - The aim of this study was to compare the in vitro caries inhibition of various
      resin-based materials. Class V cavities were prepared in twenty-five freshly
      extracted human premolar teeth which were then restored with glass-ionomer cement
      (Chemfill II), compomer (Compoglass F, Dyract AP) and composite resin (Tetric
      Ceram and Z 100). The teeth were submerged in an acid gel for 6 weeks. Each
      specimen was sectioned. These sections were left in water for 24 hours, and then
      examined using polarized light microscopy. The lesion consisted of two parts, the
      outer surface lesion and the cavity wall lesion. There was no significant
      difference in the body depth of the outer lesion and in the depth of the wall
      lesion among teeth restored with Compoglass F, Dyract AP and Chemfill II (P >
      0.05). There was a significant difference between those restored with Z 100 and
      Tetric Ceram (P < 0.05). The length of the wall lesion for the teeth restored
      with Chemfill II was significantly smaller than that in the remaining groups (P <
      0.05). The length of the wall lesion for teeth restored with Tetric Ceram and Z
      100 was significantly higher than in the remaining groups (P < 0.05). These
      results suggest that composite materials and compomer provide less caries
      inhibition than glass-ionomer cements.

PMID- 15141724
TI  - Osteoma of the condyle as the cause of limited-mouth opening: a case report.
AB  - Osteoma is a benign tumour consisting of mature bone tissue. It is an uncommon
      lesion that occurs mainly in the bones of the craniofacial complex. Only a few
      cases involving the condylar process have been reported. An osteoma of the left
      condyle causing limited mouth-opening in a 32-year-old Malaysian Chinese female
      is reported here to alert the practitioner to consider this lesion as a
      diagnostic possibility in instances of trismus or limited-mouth opening.

PMID- 15141725
TI  - Osteosarcoma presenting as an aggressive nodular mass in the region of the
      mandible.
AB  - Osteosarcomas are highly malignant neoplasms of bone that are challenging to
      diagnose. These neoplasms often show atypical behavior. In the initial phase they
      may present as nondescript bony swellings with an indolent growth rate, only to
      become overtly aggressive and malignant towards the later phase of the disease.
      Similarly, the histological growth pattern of this neoplasm can be quite diverse,
      presenting with areas that mimic benign myofibroblastic tumors, giant cell
      granulomatous conditions and partial encapsulation. The final diagnosis of an
      osteosarcoma is often reached after thorough sampling and examination of multiple
      biopsy specimens. All these clinical features and histological diagnostic
      difficulties were encountered in a case of osteosarcoma affecting the right
      mandible of a 62-year-old Chinese woman described here. The diagnostic lessons
      accrued from this case are discussed.

PMID- 15141726
TI  - Familial ossifying fibromas: report of two cases.
AB  - Ossifying fibroma is a benign fibro-osseous lesion of the jaw containing varying
      amounts of calcified deposits such as bone, cementum or both. This type of lesion
      is referred to as dysplastic or neoplastic in nature. In 2000, a 52-year-old male
      patient was referred to our clinic complaining of a giant swelling in the
      mandibular premolar-molar region. A histopathological diagnosis of ossifying
      fibroma was made. Three months later, his daughter was admitted with a swelling
      on her mandible. Following biopsy, this patient was also diagnosed as having
      ossifying fibroma. The present report describes these two cases of familial and
      multiple ossifying fibromas.

PMID- 15141727
TI  - Three-dimensional reconstruction after oral oncologic surgery using single free
      radial forearm flaps or free rectus abdominis musculocutaneous flaps.
AB  - This study reviews reconstruction of complex three-dimensional oral and
      maxillofacial defects using the single free radial forearm flap or the single
      free rectus abdominis musculocutaneous flap. Between 1996 and 2003, 124 patients
      underwent oral and maxillofacial reconstruction in the Department of Oral and
      Maxillofacial Surgery, Kobe University Graduate School of Medicine. Outcomes for
      22 patients who underwent three-dimensional reconstruction of multiple surfaces
      were evaluated. Reconstruction was performed after resection of malignant tumors
      in all 22 patients. Single FAFs were utilized for 11 patients and single RAMs for
      the remaining 11. Flap survival rate was 100%. No major donor morbidity was
      observed, and all surviving patients (20/22) were able to perform normal daily
      living activities. Single FAF and RAM are useful materials for one-stage
      reconstruction of complex three-dimensional oral and maxillofacial defects
      requiring replacement of skin, mucosa, and intervening soft tissues. Good to
      excellent aesthetic results can be attained in most patients.

PMID- 15141728
TI  - Do we need an asthma drug facility?

PMID- 15141729
TI  - The natural history of childhood intra-thoracic tuberculosis: a critical review
      of literature from the pre-chemotherapy era.
AB  - The pre-chemotherapy literature documented the natural history of tuberculosis in
      childhood. These disease descriptions remain invaluable for guiding public health
      policy and research, as the introduction of effective chemotherapy radically
      changed the history of disease. Specific high-risk groups were identified.
      Primary infection before 2 years of age frequently progressed to serious disease
      within the first 12 months without significant prior symptoms. Primary infection
      between 2 and 10 years of age rarely progressed to serious disease, and such
      progression was associated with significant clinical symptoms. In children aged
      >3 years the presence of symptoms represented a window of opportunity in which to
      establish a clinical diagnosis before serious disease progression. Primary
      infection after 10 years of age frequently progressed to adult-type disease.
      Early effective intervention in this group will reduce the burden of cavitating
      disease and associated disease transmission in the community. Although the pre
      chemotherapy literature excluded the influence of human immune deficiency virus
      (HIV) infection, recent disease descriptions in HIV-infected children indicate
      that immune-compromised children behave in a similar fashion to immune immature
      children (less than 2 years of age). An important concept deduced from the
      natural history of tuberculosis in childhood is that of relevant disease.
      Deciding which children to treat may be extremely difficult in high-prevalence,
      low-resource settings. The concept of relevant disease provides guidance for more
      effective public health intervention.

PMID- 15141730
TI  - Adapting smoking cessation interventions for developing countries: a model for
      the Middle East.
AB  - OBJECTIVE: To describe the rationale and methods for the development of
      culturally-sensitive smoking cessation interventions for primary care settings in
      developing countries. RATIONALE: Smokers in the Middle East have great difficulty
      quitting. Effective smoking cessation programs are currently lacking in the
      Middle East, and the development of culturally sensitive programs is hindered by
      the dearth of standardized information regarding tobacco use and dependence in
      this region. METHODS: Epidemiological and clinical laboratory methods are needed
      to determine the prevalence and patterns of tobacco use and nicotine dependence.
      One strategy is to adapt smoking cessation methods widely used in industrialized
      countries to the Syrian and Middle Eastern environment. In a recently initiated
      project, the Syrian Center for Tobacco Studies has been established to address
      these issues. Initial work is focusing on collecting formative data including key
      informant interviews, focus groups, and epidemiological surveys to assess
      smokers' use patterns, needs, and resources. Clinical laboratory techniques are
      also being applied to assess the physiological, behavioral, and subjective
      effects of local tobacco use methods, such as narghile (water pipe) smoking.
      These data will be used to help adapt existing smoking cessation interventions
      from industrialized countries to be evaluated in a randomized controlled trial.
      CONCLUSION: There is a great need to develop and disseminate effective cessation
      interventions in low-income countries. Successful interventions will contribute
      to a culturally sensitive and sustainable regional tobacco control
      infrastructure. This paper describes one approach to the development of such an
      infrastructure that is currently underway in the Middle East.

PMID- 15141731
TI  - Asthma management by general practitioners in Pakistan.
AB  - SETTING: Teaching university hospital in Karachi, Pakistan. OBJECTIVES: Asthma
      management guidelines have been developed to assist practising physicians in
      treating asthma patients. The objective of this study was to evaluate if the
      prescribing habits of practitioners in Karachi were consistent with the published
      asthma guidelines. DESIGN: A questionnaire survey was conducted among
      practitioners attending a pulmonary continuing medical education (CME) programme.
      Three case scenarios of asthma were given, and the doctors were asked to write a
      prescription for each case. Doctors were asked about their views on inhaler
      therapy and dietary restrictions in asthma. RESULTS: Of 120 doctors, 100 (83%)
      responded. Thirty different regimens of short acting beta2-agonist and 16
      regimens of steroid therapy were prescribed by the practitioners. Only 35% of the
      doctors prescribed corticosteroids for persistent asthma symptoms. The great
      majority of doctors were not aware of treatment options for persistent symptoms
      despite the use of preventive therapy (8% prescribed long-acting beta2-agonists,
      6% high-dose inhaled corticosteroids and 13% theophyllines). Misconceptions about
      inhaler therapy and diet were found in 20 and 50 doctors, respectively.
      CONCLUSION: General practitioners in Pakistan did not follow asthma management
      guidelines. There was serious lack of knowledge about asthma medications coupled
      with misconceptions about inhaler therapy and dietary factors.

PMID- 15141732
TI  - Estimation of annual risk of tuberculosis infection (ARTI) among children aged 1
      9 years in the south zone of India.
AB  - OBJECTIVE: To estimate the annual risk of tuberculosis infection (ARTI) among
      children aged 1-9 years in the south zone of India. SETTING: The survey was
      carried out in a representative sample of villages and census enumeration blocks
      of towns in four south Indian states, as a part of a nationwide tuberculin
      survey. DESIGN: Six districts were selected through systematic random sampling.
      Four hundred and twenty rural clusters and 180 urban clusters were selected from
      these districts on the basis of the rural-urban ratio in the entire zone. To
      obtain the required sample of 12,000 children without bacille Calmette-Guerin
      (BCG) vaccination, 51,000 had to be covered. Eighty-five children from each
      cluster were tuberculin tested and read for reaction sizes. The ARTI was computed
      from the estimated prevalence of TB infection among children without a BCG scar.
      RESULT: Among 52,951 children registered for the study, 50,846 (96%) had a
      tuberculin test result. The BCG coverage for the study population was about 65%.
      Among 17,811 children without a BCG scar, the prevalence of infection was 5.9%
      (95%CI 4.0-7.7%); the corresponding ARTI was 1.0% (95%CI 0.7-1.4%) [correction].
      CONCLUSION: The estimated ARTI for the south zone is 1.0%, as compared to the
      national average of 1.7% used for programme evaluation. This baseline information
      should be useful for the assessment of future trends.

PMID- 15141733
TI  - An economic analysis of persons with prolonged cough in rural northern Vietnam.
AB  - SETTING: Epidemiological surveillance in the Bavi district, northern Vietnam.
      OBJECTIVE: To compare the prevalences of prolonged cough across socio-economic
      groups defined by income, expenditure and official classification. To investigate
      inequalities using the Illness Concentration Index. DESIGN: Interviews in 11,547
      randomly selected households with 35,832 persons aged 15 years or more. Prolonged
      cough was identified in 559 persons (1.5%). RESULTS: Differences between cough
      prevalences were found for all socio-economic indicators, but were less clear for
      expenditure. Lower economic groups reported higher prevalences than higher
      groups, and prevalences were higher among the elderly. Male was similar to female
      prevalence. The illness gap between the poor and rich was wider for men. The
      Illness Concentration Index confirmed these findings. CONCLUSION: Inequalities
      were found when using both different socio-economic indicators and different
      analysis approaches.

PMID- 15141734
TI  - VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis
      among the Chinese Han population: a case-control study.
AB  - OBJECTIVE: To explore the potential role of vitamin D receptor (VDR) gene and
      natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms in
      susceptibility to pulmonary tuberculosis (PTB) in the Chinese Han population.
      DESIGN: In an unmatched case-control study, 120 well defined PTB patients and 240
      unrelated normal controls were enrolled. Information on potential risk factors of
      PTB was collected using a standard questionnaire. Genetic polymorphisms of VDR
      gene (TaqI and FokI) and NRAMP1 gene (INT4, D543N and 3'UTR) were analysed using
      PCR and RFLP. Unconditional logistic regression was performed, and odds ratios
      (ORs), their 95% confidence intervals (CI) and P values were estimated using
      maximum likelihood methods. RESULTS: Univariate analysis demonstrated that FokI
      ff homozygotes, D543N G/A and 3'UTR TGTG+/del heterozygotes occurred more
      frequently in patients than in controls. The crude ORs were 2.345 (95%CI 1.222
      4.499), 2.590 (95%CI 1.043-6.434) and 1.890 (95%CI 1.171-3.051), respectively,
      compared with their corresponding common genotypes. The P values were 0.033,
      0.041 and 0.030, respectively. After adjusting for exposure history and BCG
      immunisation in the multivariate analysis, the adjusted ORs were 4.625 (95%CI
      1.737-12.312), 2.415 (95%CI 1.079-8.759) and 2.187 (95%CI 1.146-4.175), with P
      values of 0.002, 0.036 and 0.018, respectively. Neither univariate nor
      multivariate analysis disclosed any significant association between the disease
      and TaqI or INT4. CONCLUSIONS: Polymorphisms in the VDR and NRAMP1 gene are
      statistically associated with susceptibility to PTB in the Chinese Han
      population.

PMID- 15141735
TI  - Gender disparity amongst TB suspects and new TB patients according to data
      recorded at the South African Institute of Medical Research laboratory for the
      Western Cape Region of South Africa.
AB  - OBJECTIVE: To describe the sex and age distribution of sputum submission and
      smear positivity in the Western Cape Province of South Africa. METHOD: Laboratory
      registers of the South African Institute of Medical Research were examined
      retrospectively for the year 1999. RESULTS: Male tuberculosis (TB) suspects
      outnumbered females by 1.45:1, whereas amongst confirmed TB cases the ratio was
      2.08:1. The odds ratio (OR) for smear positivity amongst males and females was
      1.544. The proportion of male sputum positives significantly exceeded the
      proportion of males in the general population, as measured by the 1996 census.
      Not only did the number of male TB suspects and confirmed cases exceed that of
      females in absolute terms, but the proportion of male suspects proving smear
      positive exceeded that of females. The age by sex distribution of new smear
      positive patients followed the trend reported in recent literature. CONCLUSION:
      The gendered incidence of tuberculosis identified from this census is consistent
      with that of other developing countries. However, the smaller proportion of
      female TB suspects proving smear-positive suggests a higher index of suspicion in
      females and/or longer delays prior to care seeking amongst males.

PMID- 15141736
TI  - When are follow-up sputum smears actually examined in patients treated for new
      smear-positive pulmonary tuberculosis?
AB  - SETTING: All 44 non-private hospitals (four central, 22 district and 18 mission)
      in Malawi that registered and treated tuberculosis (TB) cases, October-December
      2001. OBJECTIVES: To determine, in new smear-positive pulmonary tuberculosis
      (PTB) patients, for the 2-, 5- and 7-month smear examinations, 1) the proportion
      with smears examined and 2) the actual timing of smear examination. STUDY DESIGN:
      Retrospective data collection using TB registers, TB treatment cards and
      laboratory sputum registers. Timing of smear examinations was judged acceptable
      if 2-month smears were examined at 2 or 3 months, 5-month smears at 4, 5 or 6
      months and 7-month smears at 6, 7, 8 or 9 months. RESULTS: Of 1994 patients, for
      those alive and on treatment, 78% had smears definitely examined at 2 months, 75%
      at 5 months and 74% at 7 months. Of these, 82% had smears examined at an
      acceptable time for the 2-month smear, 71% for the 5-month smear and 78% for the
      7-month smear. Smears were examined after the 8-month treatment regimen for the 2
      and 5-month smear in respectively 2% and 9% of patients. Smears were done more
      frequently in female than male patients, and in district/mission hospitals than
      central hospitals. Smears were done at acceptable times more frequently in
      younger than older patients and in mission/central hospitals than district
      hospitals. CONCLUSION: During supervision, the actual time of follow-up sputum
      smear examinations needs to be monitored more closely.

PMID- 15141737
TI  - Effect of an HIV counseling and testing program on AIDS-related knowledge and
      practices in tuberculosis clinics in Abidjan, Cote d'Ivoire.
AB  - SETTING: Two out-patient tuberculosis treatment centers, Abidjan, Cote d'Ivoire.
      OBJECTIVE: To assess the effect of a human immunodeficiency virus (HIV)
      counseling and testing program on acquired immune-deficiency syndrome (AIDS)
      related knowledge and behaviors among persons with newly diagnosed tuberculosis.
      DESIGN: Since 1994, patients with newly diagnosed tuberculosis have received
      individual or group HIV pretest counseling, informed consent, free HIV testing
      for those who consent, and post test counseling. From January 1995 through August
      1996 in Abidjan's two largest tuberculosis clinics, knowledge and beliefs about
      HIV/AIDS were assessed before and immediately after the group pretest sessions,
      and again 4 months later. RESULTS: Prior to pretest counseling, 68.9% and 68.0%
      of the 559 enrolled subjects could correctly identify five modes of HIV
      transmission and five modes of HIV prevention. These proportions increased
      significantly immediately after pretest counseling (90.0%, 86.6%, respectively),
      and remained higher 4 months later (83.7%, 87.7%) (all P < 0.01). Among men,
      consistent condom use during the preceding 4 months with a partner who was not a
      commercial sex worker increased from 9.9% at enrollment to 23.6% at the 4-month
      visit (P = 0.001), but not for women (6.3% vs. 9.5%, P = 0.40). CONCLUSIONS: An
      HIV pretest counseling program conducted in an out-patient tuberculosis clinic
      was well accepted, and significantly increased the level of HIV/AIDS knowledge
      and, among men, self-reported condom use.

PMID- 15141738
TI  - Impact of tuberculosis on the course of HIV-infected patients with a high initial
      CD4 lymphocyte count.
AB  - OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of
      human immunodeficiency virus (HIV) infection in patients without immunological
      impairment. MATERIAL AND METHODS: In an observational study of retrospective
      cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte
      count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB.
      Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l)
      and date of starting follow-up (+/-6 months). The progression of HIV infection
      was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200
      x 10(6)/l; 2) clinical progression: time to development of acquired immune
      deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease
      progression: time to the first defined event in 1, 2 and/or 3. The times to these
      events were estimated using Kaplan Meier curves. RESULTS: There were no
      significant differences between the cohorts for age, sex and risk group. Faster
      immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression
      to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53
      9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09;
      P < 0.01) were found in the cohort of TB patients. These associations were still
      significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis
      of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x
      10(6)/l) was related to greater progression to AIDS and shorter survival.

PMID- 15141739
TI  - Current status of treatment completion and fatality among tuberculosis patients
      in Spain.
AB  - OBJECTIVES: To determine treatment completion among patients with tuberculosis
      (TB), and to analyse factors associated with treatment default and fatality.
      METHODS: A prospective cohort study of patients who began treatment between 1
      June 1999 and 31 May 2000 in areas where members of the SEPAR Tuberculosis and
      Respiratory Infections Group work. Factors associated with treatment default and
      fatality were studied using logistic regression, calculating odds ratios (OR) and
      their 95% confidence intervals (95%CI). RESULTS: The study involved 142
      physicians from 76 different hospitals who provided information on 1515 cases.
      Eighty-two per cent of the patients completed treatment correctly, 14% defaulted,
      5% died, 0.5% failed, and 8.7% interrupted treatment due to transfer or other
      reasons. The variables associated with default were intravenous drug use (IVDU)
      (OR 6.00, 95%CI 2.59-13.89) and immigration (OR 8.57, 95%CI 3.78-19.45); sex,
      age, homelessness, incarceration, directly observed treatment (DOT) or
      hospitalisation were not associated with default. Variables found to be
      predictive of fatality were alcoholism (OR 6.38, 95%CI 2.09-19.48), human
      immunodeficiency virus (HIV) infection (OR 7.08, 95%CI 2.08-29.15) and age >64
      years (OR 10, 95%CI 2.9-34.07), whereas sex, IVDU, homelessness, DOT and
      hospitalisation were not. CONCLUSIONS: In industrialised countries, IVDU patients
      and immigrants should be targeted for DOT, while to reduce fatality rates
      stricter monitoring is required for patients who are alcoholic, HIV-infected, or
      aged >64 years.

PMID- 15141740
TI  - Drug resistance trends among previously treated tuberculosis patients in a
      national registry in Peru, 1994-2001.
AB  - SETTING: National mycobacteriology reference laboratory in Peru conducting
      routine testing of susceptibility to isoniazid, rifampin, ethambutol,
      pyrazinamide, and streptomycin, in Mycobacterium tuberculosis isolates from
      previously treated patients. OBJECTIVE: To determine the percentage of isolates
      resistant to each of five anti-tuberculosis agents and to ascertain in these data
      the presence of trends of clinical relevance. DESIGN: Retrospective study of a
      national registry of M. tuberculosis isolates from patients referred for drug
      susceptibility testing between 1994 and 2001. RESULTS: Among 14,736 isolates
      tested, 10,837 (73.5%, 95%CI 72.8-74.3) demonstrated anti-tuberculosis
      resistance, and 8455 (57.4%, 95%CI 56.6-58.2) demonstrated resistance to at least
      both isoniazid and rifampin, by convention defined as multidrug-resistant
      tuberculosis (MDR-TB). A significant increasing trend could be discerned for
      resistance to each of the drugs tested and in isolates classified as MDR-TB (P <
      0.001 for trend). Additional clinically relevant trends were found in
      polyresistance and multidrug resistance percentages. CONCLUSIONS: Data from a
      national reference laboratory can be used to inform the design of retreatment
      regimens.

PMID- 15141741
TI  - Impact of a model training course for private and public specialist physicians in
      El Salvador.
AB  - BACKGROUND: Private and non-private specialist practitioners are often considered
      an obstacle to the performance of the National Tuberculosis Control Programme
      (NTP). OBJECTIVE: To evaluate the impact of an intensive refresher course
      directed at specialist physicians in El Salvador, a questionnaire was sent to all
      course participants on their basic knowledge of tuberculosis (TB) control.
      RESULTS: Of 64 participants, 55 were assessed (86%); 33 were chest physicians and
      22 belonged to other related specialities. The evaluation showed a considerable
      improvement in both groups in their ability to suspect the disease, in their
      tendency to avoid hospitalising patients and instead refer them to out-patient
      clinics, and in their adherence to the recommendations of the NTP manual
      (diagnostic procedures, treatment guidelines, case notification and cohort
      studies). Improvements were more noticeable, in all the parameters evaluated,
      among the non-chest physicians. CONCLUSION: The intervention model succeeded in
      improving the collaboration of private and non-private specialist practitioners
      with the NTP.

PMID- 15141742
TI  - Directly observed therapy for tuberculosis in New York City: factors associated
      with refusal.
AB  - OBJECTIVES: To describe patients who utilize hospital-based directly observed
      therapy (DOT) programs and to describe factors that influence refusal of DOT.
      METHODS: Retrospective analysis of patients diagnosed with tuberculosis through
      hospital admission in 1997 at 12 hospital sites with out-patient DOT programs.
      Data were obtained from hospital patient records and from the New York City
      Tuberculosis Case Registry. RESULTS: Of 443 patients diagnosed with tuberculosis
      in 1997 at the 12 hospital sites and available and/or eligible for DOT, 52 (12%)
      refused DOT. The two main reasons for DOT refusal were that the patients felt
      they could self-medicate (21%) and that their work schedule interfered with a DOT
      program (19%). White non-Hispanic race/ethnicity was associated with refusal of
      DOT (P = 0.001). Conversely, interview for DOT while in the hospital (P < 0.001)
      and enrollment in drug treatment were associated with acceptance of DOT (P =
      0.05). The five hospitals with tuberculosis clinics on site had the lowest
      percentages (0-9%) of patients refusing DOT. CONCLUSION: To increase patient
      acceptance of DOT, programs need flexible hours that accommodate patients in the
      workforce. Patient education should focus on the difficulty of completing
      tuberculosis treatment on a self-administered regimen and the importance of the
      support offered through DOT.

PMID- 15141743
TI  - Clinical and demographic aspects of extrathoracic tuberculosis: experience of an
      Italian university hospital.
AB  - OBJECTIVE: The decline of tuberculosis in industrialised countries concerns
      mainly its pulmonary forms. We have analysed all the cases of non-respiratory
      tuberculosis admitted to our hospital between January 2000 and June 2002, and
      compared epidemiological, clinical and diagnostic features in our area with those
      observed in other industrialised countries with high immigration rates. DESIGN:
      Patients' records were retrospectively analysed for demographic, clinical,
      laboratory and instrumental data. Delays in the introduction of treatment were
      also measured. Characteristics of immigrants were compared with those of native
      born persons. We also investigated specific features of extrathoracic
      tuberculosis affecting different body sites. RESULTS: Forty-eight patients were
      identified, two thirds of whom were from industrialised countries. Age
      distribution was characteristically bimodal. Vertebral (n = 18) and lymph node (n
      = 11) tuberculosis were the most frequently detected forms. The therapeutic delay
      among individuals from industrialised countries was found to be significantly
      longer than that of their counterparts from developing countries (P = 0.05).
      CONCLUSION: We hypothesise that the complex and non-standardised diagnostic
      approach to the different forms of extrathoracic tuberculosis forms and
      physicians' lack of awareness of the specific risk of each epidemiological group
      strongly influence the unacceptably long therapeutic delay. Extrathoracic
      tuberculosis was more neglected in native-born individuals than in immigrants.

PMID- 15141744
TI  - Clinical characteristics of 110 miliary tuberculosis patients from a low HIV
      prevalence country.
AB  - SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To
      define the clinical characteristics and outcome of miliary tuberculosis (TB)
      patients from a low human immunodeficiency virus (HIV) prevalence country.
      DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001.
      Clinical characteristics of those dying from miliary TB were compared with those
      of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or
      elderly, with a female preponderance. An underlying medical condition was present
      in 47%. Presenting symptoms were of several weeks' duration, and mostly
      constitutional (fever and weight loss). Common laboratory findings included
      anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline
      phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was
      observed in 77% of radiographs. Sputum smear and culture were positive in
      respectively 36% and 52% of those tested. Biopsy was performed in selected
      patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died
      were significantly older than survivors and had a more fulminant course. Presence
      of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the
      need for ventilation were associated with increased mortality. CONCLUSION:
      Miliary TB carries a high mortality. It should be considered in patients who
      present with prolonged systemic symptoms. A positive TB culture or biopsy is
      needed to establish a diagnosis.

PMID- 15141745
TI  - Bioavailability of rifampicin in Indonesian subjects: a comparison of different
      local drug manufacturers.
AB  - To examine the bioavailability of rifampicin formulations produced in Indonesia,
      we conducted a single-dose, double-blind, cross-over bioavailability study.
      Antituberculosis drugs from three Indonesian manufacturers and one international
      manufacturer were compared in 12 healthy Indonesian subjects. Out of three local
      manufacturers, two showed equal bioavailability compared to the reference
      standard, and one showed slightly lower bioavailability (ratio 0.86; 90%
      confidence interval 0.80-0.91) and substandard rifampicin content of drug
      preparations. Plasma rifampicin concentrations in this study were more than three
      fold higher than concentrations recently found in tuberculosis patients in
      Indonesia, which suggests that unknown (disease-related) determinants may reduce
      the bioavailability of rifampicin formulations.

PMID- 15141746
TI  - Indigenous NGO involvement in TB treatment programmes in high-burden settings:
      experiences from the Northern Cape province, South Africa.
AB  - Effective tuberculosis (TB) treatment delivery in high-burden countries
      increasingly requires a multisectoral approach. This paper examines the role two
      local non-governmental organisations (NGOs) play in TB care delivery in a high
      burden setting, the Northern Cape province, South Africa. NGOs played a
      complementary role to the formal health sector in effecting TB treatment delivery
      by training facilitators and recruiting and training lay volunteers for directly
      observed treatment. One key challenge was the paucity of systematised information
      to enable rigorous evaluation of the effectiveness of NGO contribution, which led
      to inadequate funding, as potential donors were sceptical about supporting
      activities whose value they could not assess. In high disease burden settings,
      where auxiliary actors can play useful roles in effective service delivery, it is
      important for NGOs to document and self-evaluate their role. One way of building
      this capacity is through technical support by government and development
      partners.

PMID- 15141747
TI  - Verrucous carcinoma of the ear: an uncommon and difficult lesion.

PMID- 15141748
TI  - Quality of life following neck dissections.

PMID- 15141749
TI  - Crohn's disease manifesting in the head and neck.
AB  - Crohn's disease may present to the head and neck surgeon with symptoms and signs
      attributed to the disease. Many clinical presentations, both specific and non
      specific, have been recorded in the oral cavity, nose and larynx. Some of these
      clinical manifestations have been found to be consistent with Crohn's disease,
      but most have been attributed to Crohn's disease without histologic confirmation
      of the presence of non-caseating granulomas, which is pathognomonic of Crohn's
      disease. Lesions, when present without an associated diagnosis of Crohn's
      disease, should be ascribed the diagnosis of orofacial granulomatosis, until a
      diagnosis of intestinal Crohn's disease has been confirmed.

PMID- 15141750
TI  - Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications
      for the correlation of hearing loss phenotype with mutant type XI collagen
      genotype.
AB  - OBJECTIVE: Mutations in the fibrillar collagen genes COL11A1 and COL11A2 can
      cause sensorineural hearing loss associated with Stickler syndrome. There is a
      correlation of hearing loss severity, onset, progression and affected frequencies
      with the underlying mutated collagen gene. We sought to determine whether
      differences in spatial or temporal expression of these genes underlie this
      correlation, and to identify the cochlear cell populations expressing these genes
      and the structures likely to be affected by mutations. MATERIALS AND METHODS: We
      used in situ hybridization analysis of C57BL/6J mouse temporal bones. RESULTS:
      Similar, diffuse expression of Col11a1 and Col11a2 mRNA was first observed in the
      cochlear duct at embryonic Day 15.5, with increasingly focal hybridization being
      noted at postnatal Days 1 and 5 in the greater epithelial ridge and lateral wall
      of the cochlea. The greater epithelial ridge appeared to be the main, if not
      only, source of mRNA encoding Col11a1 and Col11a2 in the tectorial membrane. At
      postnatal Day 13, Col11a1 and Col11a2 expression became more focal and co
      localized in the inner sulcus, Claudius' cells and cells of Boettcher.
      CONCLUSIONS: We did not observe spatial or temporal differences in mRNA
      expression that could account for the auditory phenotype genotype correlation.
      The expression patterns suggest essential roles for Col11a1 and Col11a2 in the
      basilar or tectorial membranes.

PMID- 15141751
TI  - Vestibular involvement in myringitis bullosa.
AB  - OBJECTIVE: Cochlear involvement manifested by sensorineural or mixed-type hearing
      loss (HL) has been reported to occur in 30-67% of patients suffering from
      myringitis bullosa (MB). The goal of this study was to investigate the incidence
      and nature of vestibular involvement in MB. MATERIAL AND METHODS: All adult
      patients presenting to Hadassah University Hospital with MB between 2000 and 2002
      were evaluated for inner ear involvement. Audiometry, tympanometry and
      electronystagmography (ENG) were performed within the first 48 h after
      presentation. The affected ears were examined on a regular basis and audiometric
      studies were repeated every other day. ENG was not repeated but a detailed
      questionnaire was administered and a thorough physical examination performed to
      rule out persistent vestibular dysfunction. RESULTS: Thirteen patients (17 ears)
      were diagnosed as suffering from MB. All 13 patients reported HL in the affected
      ears and 7 (54%) reported a sensation of vertigo at presentation. Audiometric
      tests revealed HL in all 17 affected ears: sensorineural HL in 2, mixed-type HL
      in 12 and conductive HL in 3. ENG was normal in only two cases, both of whom did
      not suffer from vertigo. Four patients with no vestibular symptoms whatsoever had
      an abnormal electronystagmogram. All seven patients who complained of vertigo had
      an abnormal electronystagmogram and recovered fully after treatment. All but two
      patients recovered their auditory function. CONCLUSIONS: Not only is the cochlear
      part of the inner ear affected in patients suffering from MB, but the vestibular
      part as well. Sensorineural HL and vestibular abnormalities should both be
      considered as manifestations of MB.

PMID- 15141752
TI  - Reconstruction of mastoid cortex defect using bone morphogenetic protein: an
      experimental study in the guinea pig.
AB  - OBJECTIVE: The aim of this experimental study was to examine whether recombinant
      human bone morphogenetic protein-2 (rhBMP-2) could induce new bone formation in a
      small hole drilled through the temporal bone near the external auditory canal
      wall in guinea pigs. MATERIAL AND METHODS: A 4-mm diameter hole was made in the
      center of the temporal bone and a piece of collagen sheet infiltrated with rhBMP
      2 was placed in the hole. New bone formation was confirmed by means of X-ray
      examination and the bone mineral density was quantified using dual-energy X-ray
      absorptiometry 1, 2 and 4 weeks after treatment. RESULTS: The bone mineral
      density in the rhBMP-2-treated group was significantly increased compared to the
      control group. CONCLUSION: These results suggest that rhBMP-2 induces remarkable
      new bone formation in the temporal bone and will be useful in clinical ear
      surgery.

PMID- 15141753
TI  - A novel mitochondrial mutation, 1556C --> T, in a Japanese patient with
      streptomycin-induced tinnitus.
AB  - OBJECTIVE: Aminoglycoside antibiotics are associated with ototoxicity. The 1555A 
      -> G mutation in the 12S ribosomal RNA gene of mitochondrial DNA has been
      considered to be associated with susceptibility to aminoglycoside antibiotics. In
      this study we examined a 79-year-old Japanese patient with a 45-year history of
      streptomycin-induced tinnitus in an attempt to find a mitochondrial mutation.
      MATERIALS AND METHODS: DNA was extracted from the patient's leukocytes.
      Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      screening for the 1555A --> G mutation was done in order to detect a
      mitochondrial mutation and then nucleotide sequencing analysis was performed to
      identify the mutation. RESULTS: PCR-RFLP screening detected the presence of a
      mitochondrial mutation in the patient. However, the nucleotide sequencing
      analysis showed that the mutation was not the 1555A --> G mutation but a novel
      mutation, 1556C --> T. The mutation was not found in 112 unrelated Japanese
      control subjects, suggesting that the mutation was specific to our patient.
      CONCLUSIONS: The 1556C --> T mutation may be a genetic risk factor for
      aminoglycoside-induced hearing impairment. Our result also suggests that patients
      with the 1556C --> T mutation exist among those expected to have the 1555A --> G
      mutation as a result of PCR-RFLP analysis.

PMID- 15141754
TI  - Background on methods of stimulation in galvanic-induced body sway in young
      healthy adults.
AB  - The aim of this study was to develop a standardized procedure for reproducible
      quantification of galvanic-induced body sway (GBS). This was a prospective
      experimental study conducted in a tertiary referral centre. An exploratory study
      was first conducted to define the galvanic vestibular stimulation (GVS) method
      that resulted in the best reproducible responses. Ten subjects underwent computer
      controlled GVS using five different types of monaural and binaural stimulation
      with 2-mA currents. Cosinusoidal stimulation gave the most reproducible
      responses. The frequency and current variability of this stimulus type were then
      tested in the same 10 subjects. A monaural continuous 1-cosinusoidal current of
      0.5 Hz and 2 mA gave the most reproducible responses (< 20% test-retest
      variation) and the largest GBS amplitude. The other (sinusoidal) stimuli resulted
      in variabilities exceeding 50%. This stimulus was thus used for further testing
      in our normative study. In this study we measured GBS amplitude at 0.5 Hz in 60
      subjects, with eyes closed and an inter-feet distance of 0 cm, using a force
      platform. In addition to body sway, responses included slight dizziness, taste
      sensations and a tingling sensation at the site of stimulation. Habituation to
      the applied stimulus was seen. Binaural prestimulation, performed in 50/60 test
      subjects, is necessary to reduce habituation and achieve optimal reproducibility
      in order to be able to compare the sensitivity of the left and right vestibular
      systems. The test-retest variability was determined in detail in 12 additional
      subjects. Prestimulation reduced habituation, but improved the sensitivity of the
      method; some test-retest variability persisted (< 20%).

PMID- 15141755
TI  - Conservation of low-frequency hearing in cochlear implantation.
AB  - OBJECTIVES: As results with cochlear implants have continued to improve, patients
      with some remaining cochlear function have become eligible for cochlear
      implantation. Thus, preservation of acoustic hearing after implantation has
      gained importance. Hearing preservation can be considered a benchmark for
      atraumatic implantation preventing neural degeneration from loss of residual hair
      cells or subsequent to local trauma. In this prospective study, the possibility
      of preserving low-frequency hearing in cochlear implantation using a modified
      surgical technique has been explored. MATERIAL AND METHODS: In a prospective
      study design, 14 subjects with considerable low-frequency hearing of 20-60 dB in
      the frequency range 125-500 Hz but with unsatisfactory speech understanding with
      hearing aids of < 35% monosyllabic word understanding were implanted with a MED
      EL COMBI-40+ cochlear implant. The insertion depth was intentionally limited to
      19-24 mm to prevent damage to low-frequency regions of the cochlea. Pre- and
      postoperative pure-tone thresholds were measured. RESULTS: Hearing was conserved
      within 0-10 dB in 9/14 subjects and within 11-20 dB in 3/14; in 2/14 subjects
      hearing was completely lost in the implanted ear. Thus hearing could at least
      partially be conserved in 12/14 subjects (86%). Median threshold values decreased
      by 10, 15, 17.5 and 5 dB at 125, 250, 500 and 1000 Hz, respectively. Even high
      levels of hearing, e.g. 30 dB at 500 Hz, could be maintained after implantation
      in some subjects. CONCLUSIONS: This study reports successful conservation of
      hearing after cochlear implantation using a modified surgical technique. Even
      high levels of hearing could be maintained, showing that implantation of an
      intracochlear electrode can be performed atraumatically with preservation of
      functional structures.

PMID- 15141756
TI  - Basic fitting and evaluation parameters of a newly designed cochlear implant
      electrode.
AB  - OBJECTIVE: To validate a newly designed cochlear implant electrode (TRACE) in the
      standard monopolar mode and compare it to a patient group implanted with a
      standard Nucleus Contour cochlear implant electrode. The electrode contacts of
      the TRACE electrode have the same active surface area for stimulation, but the
      position in the scala tympani is different from that of the Nucleus Contour
      electrode. MATERIAL AND METHODS: The following parameters, used in cochlear
      implant fitting and evaluation procedures, were determined: the threshold and
      comfort stimulation current levels; the electrode impedances; and the phoneme
      discrimination and speech recognition scores using the ACE speech algorithm.
      CONCLUSION: The new electrode does not differ significantly from the standard
      Nucleus Contour electrode in terms of the investigated parameters within the test
      group.

PMID- 15141757
TI  - Does static ear canal pressure influence pure tone pitch perception?
AB  - OBJECTIVE: That static ear canal air pressure (ECP) influences the frequency of
      spontaneous otoacoustic emissions (SOAEs) suggests that it may influence
      intracochlear, in addition to middle ear, processes. A previous study suggested
      that ECP influences pure tone pitch perception at 1,000 Hz, which was interpreted
      as indicating an effect on the cochlear place-frequency map. The present study
      extended investigations of this effect to 500 and 4,000 Hz. MATERIAL AND METHODS:
      Nine normal-hearing listeners performed interaural pitch matching with monaural
      ECPs of 0 and -300 daPa. RESULTS: Some indications of a small downward pitch
      shift (mean 0.2%) at 500 Hz were observed, which were marginally statistically
      significant at the 5% level. No pitch shifts were observed at 4,000 Hz.
      CONCLUSIONS: ECP does not influence pitch to the extent suggested previously or
      by SOAE frequency shifts. No evidence was found to support the notion that ECP
      influences the place-frequency map.

PMID- 15141758
TI  - Polysomnographic effects of nasal surgery for snoring and obstructive sleep
      apnea.
AB  - OBJECTIVE: It has been hypothesized that nasal obstruction causes an increase in
      negative pressure in the upper airway and induces an inspiratory collapse at the
      pharyngeal level. We used portable polysomnography (PSG) to assess the efficacy
      of nasal surgery for snoring and obstructive sleep apnea (OSA). MATERIAL AND
      METHODS: We reviewed 21 patients who presented with nasal obstruction and
      snoring. Septal surgery with or without inferior turbinectomy was performed. Each
      patient was assessed pre- and postoperatively using PSG. We measured the
      respiratory distress index (RDI), apnea index (AI), oxygen saturation index (OSI)
      and the duration of snoring. Selection criteria were an RDI of > 15 as determined
      by PSG and clinical nasal obstruction and a deviated nasal septum as determined
      by physical examination. RESULTS: Nasal surgery had the following effects: RDI
      decreased from 39 to 29 (p = 0.0001), AI decreased from 19 to 16 (p = 0.0209),
      OSI decreased from 48 to 32 (p = 0.0001) and the duration of snoring decreased
      from 44% to 39% (p = 0.1595). Snoring and OSA were completely relieved in 4
      patients (19%) who did not require any additional surgical therapy. CONCLUSION:
      Snoring and OSA may be corrected merely by septal surgery in some patients, and
      secondary surgery (uvulopalatoplasty) may be considered after a thorough
      evaluation by means of postoperative PSG.

PMID- 15141759
TI  - Laryngeal hamartoma.
AB  - OBJECTIVE: Hamartoma is a rare finding in the head and neck area and usually
      occurs as an age-related tumor in the lung. The aim of this study was to present
      the results of long-term follow-up of a case of laryngeal hamartoma (LH) and
      review the relevant literature. MATERIAL AND METHODS: A case of LH is presented
      which occurred in a 5-year-old child with a previously unreported change in the
      histologic pattern at recurrence. The relevant literature is critically reviewed
      with emphasis on histopathological aspects, clinical signs, age and gender.
      RESULTS: A total of 26 patients matched the search criteria, of whom 17 (65%)
      were male. LH occurred in 10 children (mean age 1.9 years) and 9 adults (mean age
      49.6 years). Stridor, dysphonia and hoarseness were the commonest symptoms,
      occurring in 14 patients in total. In 18 patients the tumor presented as a
      supraglottic lesion (69%). Two neonates died shortly after the diagnosis was
      made. The current patient is the first to have presented with a change in the
      histological subtype. CONCLUSION: LH should be included in the differential
      diagnosis of benign laryngeal lesions, particularly in children. Complete
      surgical removal is the method of choice but should be limited in order to
      preserve laryngeal function, as the prognosis of patients with LH is excellent.

PMID- 15141760
TI  - Type 2 thyroplasty for spasmodic dysphonia: fixation using a titanium bridge.
AB  - OBJECTIVE: In order to facilitate surgery for spasmodic dysphonia, i.e. type 2
      thyroplasty, a device was designed to fix the incised edges of the thyroid
      cartilage firmly. MATERIAL AND METHODS: Various types and sizes of titanium
      bridge were developed for clinical use. RESULTS: The results of surgery for
      spasmodic dysphonia were satisfactory in all 10 cases in which the new titanium
      bridge was used. No complications have been encountered to date. CONCLUSION: Type
      2 thyroplasty for spasmodic dysphonia was made easier to perform using the new
      titanium bridge, and more stable fixation of the reconstructed thyroid cartilage
      was achieved.

PMID- 15141762
TI  - MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland.
AB  - Non-disseminated malignant lymphomas of salivary glands occurring in association
      with Warthin's tumour have rarely been reported. We describe the first case of
      association of an extranodal mucosa-associated lymphoid tissue (MALT)-type non
      Hodgkin's lymphoma with Warthin's tumour of the parotid gland. Total
      parotidectomy with preservation of the facial nerve was performed. Surgical and
      pathological evidence confirmed that the parotid MALT lymphoma did not arise in
      the lymphoid stroma of the Warthin's tumour. Immunostaining of the MALT lymphoma
      cells proved negative for Epstein-Barr virus and Helicobacter pylori antibodies
      and polymerase chain reaction assays did not identify human herpesvirus 8. The
      patient has been followed up for 11 months, without evidence of recurrent
      disease. It cannot be ruled out that long-term immunological stimulation by the
      Warthin's tumour may have caused lymphoid accumulation, chronic stimulation of B
      cells and extranodal parotid MALT lymphomagenesis.

PMID- 15141763
TI  - A rapidly progressing periorbital mass in an infant: fasciitis nodularis.
AB  - Nodular fasciitis is a benign, rapidly growing proliferation of fibroblasts,
      which is histologically difficult to distinguish from neoplasms. In several
      reports, as many as half of all cases have been initially misdiagnosed as a
      fibrosarcoma or some other malignancy. Although the head and neck is a region of
      predilection in infants and children, only eight periocular lesions have
      previously been reported in paediatric patients. We present a case of nodular
      fasciitis which occurred in the periorbital region in a 1 1/2-year-old girl. The
      process was excised locally in order to perform a biopsy. The mass was initially
      classified as a sarcoma but subsequently as infantile fibromatosis. Only after a
      thorough review of the case and four independent pathological consultations was
      the final diagnosis of nodular fasciitis confirmed. No further treatment was
      scheduled. Although the primary surgical removal of the tumour was not radical,
      no recurrence was observed during a 3-year follow-up period.

PMID- 15141761
TI  - Inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral
      nerves of mice treated with doxorubicin and vinblastine.
AB  - OBJECTIVE: To investigate the inhibitory effect of cyclosporin A on p
      glycoprotein function in peripheral nerves (VIIth, VIIIth and sciatic nerves).
      MATERIAL AND METHODS: Male mdr1a(-/-) and mdr1a(+/+) FVB mice were used.
      Doxorubicin (30 mg/kg) was administered intravenously with or without i.p.
      administration of cyclosporin A (200 mg/kg). Vinblastine (5 mg/kg) was also
      administered intravenously with or without i.p. administration of cyclosporin A
      (200 mg/kg). RESULTS: Tissue concentrations of doxorubicin and vinblastine in
      peripheral nerves of the mdr1a(+/+) mice pretreated with 200 mg/kg cyclosporin A
      were significantly higher than those in the mdr1a(+/+) mice administered
      doxorubicin or vinblastine alone, suggesting that cyclosporin A inhibited the
      efflux pump function of p-glycoprotein in the peripheral nerves. In the mdr1a(-/
      ) mice, tissue concentrations of doxorubicin and vinblastine in peripheral nerves
      were also significantly higher than those in the mdr1a(+/+) mice administered
      doxorubicin or vinblastine alone. Based on these results, it is suggested that p
      glycoprotein plays an important role in blood-nerve barrier function by
      preventing side-effects induced by neurotoxic drugs. CONCLUSION: When doxorubicin
      and vinblastine are co-administered with cyclosporin A, the patient should be
      carefully monitored because peripheral nerve disorders may be induced.

PMID- 15141764
TI  - Congenital aplasia of the parotid gland with omolateral cheek angioma: case
      report and review of the literature.
AB  - Congenital agenesis of the parotid gland is a rare entity whose etiopathogenesis
      is still unclear. It is usually bilateral and is sometimes associated with other
      developmental anomalies of the head and neck region. A case is presented in which
      aplasia of the right parotid gland was associated with an omolateral angioma of
      the cheek. The radiological diagnostic approach and a review of the literature on
      agenesis of the salivary glands are presented.

PMID- 15141765
TI  - Maxillary sinus cavernous hemangioma: a rare entity.
AB  - Vascular lesions of the sinonasal tract are rare. These lesions do not have
      typical signs or symptoms. They may present insidiously with minimal symptoms. A
      high index of suspicion and a good preoperative evaluation are needed for
      diagnosis. No standard surgical approach is indicated. We report a case of
      cavernous hemangioma of the maxillary sinus in an adult male. We present the
      diagnostic work-up and discuss the differential diagnosis and potential
      therapeutic approaches.

PMID- 15141767
TI  - On finding happiness.

PMID- 15141766
TI  - Re: Effects of loratadine... by Andersson et al.

PMID- 15141768
TI  - Holding expert witnesses accountable for their actions and opinions.

PMID- 15141769
TI  - Lewis and Clark treat a case of paralysis: speculation on the etiology of the
      problem.
AB  - In their monumental journey across North America and back, the explorers Lewis
      and Clark encountered and treated a Native American Chief with flaccid paralysis
      of about five years duration. The etiology of the paralysis is unclear from the
      historical sources. Intracranial, spinal cord, neuropathic, neuromuscular and
      muscular diagnoses are possible. The diagnosis that appears best to fit the case,
      however, is conversion disorder. In spite of limited diagnostic and treatment
      resources, the unfortunate man was apparently treated successfully.

PMID- 15141770
TI  - Spinal cord injuries due to falls from hunting tree stands in Oklahoma, 1988
      1999.
AB  - Serious injuries resulting in paralysis or death have been shown to occur to
      hunters who have sustained falls from tree stands. A total of sixteen spinal cord
      injuries or deaths among Oklahoma hunters falling from tree stands were reported
      between 1987 and 1999. The mean height of the falls was 16.4 feet. Three (18.8%)
      of the cases were related to substance use. None of the patients were using a
      safety restraint. Nearly 90% of the injuries resulted in paraplegia/paresis; two
      (12.5%) of the injuries resulted in death. Forty-four percent of the spinal
      injuries occurred at the thoraco-lumbor junction (T12 or L1). Burst fractures
      were the most common fracture pattern. Hospitalizations averaged 19.6 days (range
      3 to 73 days) and eight (50%) were discharged to inpatient rehabilitation
      facilities. Falls from tree stands can result in serious injuries or death.
      Hunter education and the use of safety harnesses for prevention of injuries
      related to tree stands are paramount.

PMID- 15141771
TI  - Prevention of head injuries in children bicyclists: a proposal.
AB  - Bicycle-related head injury is a significant source of morbidity in children.
      Upon review of contemporary approaches for reducing such injuries, summarized
      herein, the authors conclude that a school-based promotion of proper helmet usage
      represents a reasonable compromise between expediency and probability of success.
      This proposal contains an outline for a pilot program to be implemented in an
      elementary school setting. It is postulated that a large-scale implementation of
      this program in combination with other discussed interventions will achieve the
      long-term goal of reducing bicycle-related pediatric head injuries.

PMID- 15141772
TI  - HIPAA: lingering privacy issues.

PMID- 15141773
TI  - It's time to start thinking about the HIPAA security regulations!

PMID- 15141774
TI  - The Emperor's New Groove.

PMID- 15141775
TI  - Forecasting recidivism in mentally ill offenders released from prison.
AB  - Little research has focused on assessing the risk of mentally ill offenders
      (MIOs) released from state prisons. Here we report findings for 333 mentally ill
      offenders released from Washington State prisons. Logistic regression identified
      sets of variables that forecasted felony and violent reconviction as accurately
      as state-of-the-art risk assessment instruments. Sums of simple recoded versions
      of these variables predicted reoffense as well as complex logistic regression
      equations. Five of these 9 variables were found to be relative protective
      factors. Findings are discussed in terms of the value of stock correctional
      variables in forecasting risk, the need to base actuarial risk assessments on
      local data, the importance of protective factors in assessing MIO risk, and the
      need for dynamic, situational, and clinical variables that can further sharpen
      predictive accuracy of emergent risk in the community.

PMID- 15141776
TI  - What makes a good alibi? A proposed taxonomy.
AB  - A taxonomy of alibis is proposed involving two forms of supporting proof:
      physical evidence and person evidence. Levels of physical evidence and person
      evidence were combined to create 12 cells in the taxonomy. Participants (n =
      252), who were asked to assume the role of detectives, evaluated alibis
      representing these 12 cells. The believability of the alibis generally followed
      the taxonomy's predicted pattern, but physical evidence, when present, tended to
      overwhelm the person evidence more than had been expected. In addition, alibi
      evaluators seemed to not consider the possibility that a stranger who
      corroborated an alibi might be mistaken about the identity of the person. Trait
      inferences regarding the alibi providers tended to follow the believability data,
      even when the traits themselves were not relevant to believability of the alibi.
      We call for the development of a literature on the psychology of alibis,
      recommend the taxonomy as a framework, and suggest several avenues of inquiry.

PMID- 15141778
TI  - The role of trust in nurturing compliance: a study of accused tax avoiders.
AB  - Why an institution's rules and regulations are obeyed or disobeyed is an
      important question for regulatory agencies. This paper discusses the findings of
      an empirical study that shows that the use of threat and legal coercion as a
      regulatory tool--in addition to being more expensive to implement--can sometimes
      be ineffective in gaining compliance. Using survey data collected from 2,292
      taxpayers accused of tax avoidance, it will be demonstrated that variables such
      as trust need to be considered when managing noncompliance. If regulators are
      seen to be acting fairly, people will trust the motives of that authority, and
      will defer to their decisions voluntarily. This paper therefore argues that to
      shape desired behavior, regulators will need to move beyond motivation linked
      purely to deterrence. Strategies directed at reducing levels of distrust between
      the two sides may prove particularly effective in gaining voluntary compliance
      with an organization's rules and regulations.

PMID- 15141777
TI  - Property crime victims' decision to notify the police: social, cognitive, and
      affective determinants.
AB  - Previous research suggests that 3 general processes underlie the decision of
      property crime victims to notify the police: One that is cognitively driven by
      reward/cost considerations, one that is affectively driven, and another that is
      socially driven. This study is the first to employ a community sample of crime
      victims to compare the 3 processes within a single study. Computer-assisted
      interviews were conducted with 422 property crime victims (n = 129 burglary, n =
      293 theft) located via a random digit dialing procedure. Logistic regression
      analyses showed that each process independently accounted for a significant
      amount of the variance in victim reporting, and that there were no interactions
      among the three processes in predicting reporting. Of the 3 processes, social
      influence was the best predictor of reporting. Analysis of the affect-driven
      process showed that reporting was primarily a function of the level of fear
      rather than anger or the level of generalized arousal upon discovering the crime.

PMID- 15141779
TI  - Why people waive their Miranda rights: the power of innocence.
AB  - In a laboratory experiment, 72 participants who were guilty or innocent of a mock
      theft were apprehended for investigation. Motivated to avoid prosecution and
      trial, they were confronted by a neutral, sympathetic, or hostile male
      "detective" who sought a waiver of their Miranda rights. Later, 72 other
      participants watched videotapes of these sessions and answered questions about
      the detective and suspect. Strikingly, results showed that although the
      detective's demeanor had no effect, participants who were truly innocent were
      significantly more likely to sign a waiver than those who were guilty. Naively
      believing in the power of their innocence to set them free, most waived their
      rights even in the hostile detective condition, where the risk of interrogation
      was apparent. The conceptual and policy implications of these results are
      discussed.

PMID- 15141780
TI  - Marijuana odor perception: studies modeled from probable cause cases.
AB  - The 4th Amendment of the United States Constitution protects American citizens
      against unreasonable search and seizure without probable cause. Although law
      enforcement officials routinely rely solely on the sense of smell to justify
      probable cause when entering vehicles and dwellings to search for illicit drugs,
      the accuracy of their perception in this regard has rarely been questioned and,
      to our knowledge, never tested. In this paper, we present data from two empirical
      studies based upon actual legal cases in which the odor of marijuana was used as
      probable cause for search. In the first, we simulated a situation in which,
      during a routine traffic stop, the odor of packaged marijuana located in the
      trunk of an automobile was said to be detected through the driver's window. In
      the second, we investigated a report that marijuana odor was discernable from a
      considerable distance from the chimney effluence of diesel exhaust emanating from
      an illicit California grow room. Our findings suggest that the odor of marijuana
      was not reliably discernable by persons with an excellent sense of smell in
      either case. These studies are the first to examine the ability of humans to
      detect marijuana in simulated real-life situations encountered by law enforcement
      officials, and are particularly relevant to the issue of probable cause.

PMID- 15141781
TI  - Risk factors for the development versus maintenance of posttraumatic stress
      disorder.
AB  - This study examined risk factors for posttraumatic stress disorder (PTSD) in
      Vietnam veterans: 68 women and 414 men of whom 88 were White, 63 Black, 80
      Hispanic, 90 Native Hawaiian, and 93 Japanese American. Continuation ratio
      logistic regression was used to compare the predictive power of risk factors for
      the development versus maintenance of full or partial PTSD. The development of
      PTSD was related to premilitary, military, and postmilitary factors. The
      maintenance of PTSD was related primarily to military and postmilitary factors.
      Multivariate analyses identified different models for development and
      maintenance. We conclude that development of PTSD is related to factors that
      occur before, during, and after a traumatic event, whereas failure to recover is
      related primarily to factors that occur during and after the event.

PMID- 15141782
TI  - International publication trends in the traumatic stress literature.
AB  - This analysis looked at international publication trends in the field of trauma
      by examining first author affiliations of over 13,000 trauma publications from
      1987 to 2001. Searches were conducted using the Published International
      Literature on Traumatic Stress (PILOTS) database to determine frequency of
      international contributions. A similar search of the Journal of Traumatic Stress
      (JTS) was also conducted. Although the majority of trauma research comes from
      investigators in North America, examining publication trends over time revealed
      that trauma research is becoming increasingly international in its
      representation. Results suggest that of the overall trauma literature, 36% of
      contributions come from authors outside North America. Likewise, among JTS
      publications over the first 14 years of circulation, 27% came from authors
      outside North America. More recent publication years reflect higher levels of
      international contributions for both sources. The majority of trauma research
      published over the 15-year span was in English. Implications for the field of
      traumatic stress research are discussed.

PMID- 15141783
TI  - Social attitudes toward traumatized men and women: a vignette study.
AB  - This study investigated social beliefs about gender-appropriate reactions to
      trauma. Ninety-three men and 179 women completed vignette measures of attitudes
      toward victims, the Bem Sex Role Inventory, and the Trauma History Questionnaire.
      Participants evaluated male victims less favorably than female victims. Women
      responded more positively toward all victims than men. Participants regarded
      female crime victims more positively than their male counterparts, but did not
      distinguish between male and female natural disaster victims. Feminine-sex-typed
      women rated victims more favorably than masculine-sex-typed individuals. There
      was a positive relation between personal trauma exposure and attitudes toward
      male victims among male participants. These findings contribute to an
      understanding of factors influencing the social reactions experienced by
      traumatized men and women, and have implications for clinical practice and
      psychoeducation.

PMID- 15141784
TI  - Trauma exposure and retention in adolescent substance abuse treatment.
AB  - Trauma exposure and related symptoms interfere with adult adherence to drug
      treatment. Whether these findings hold true for adolescents is unknown. We
      examined trauma exposure, PTSD symptoms, and psychosocial functioning among 212
      adolescents upon admission to long-term residential drug treatment and examined
      retention in treatment at 6 months. Seventy-one percent reported lifetime trauma
      exposure, and 29% of the trauma-exposed met criteria for current PTSD. Trauma
      exposed adolescents reported more behavioral problems, with gender differences
      apparent. We divided the sample into three groups: no trauma exposure (21%),
      trauma-exposed without PTSD (59%), and trauma-exposed with PTSD (20%). Survival
      analysis showed that trauma-exposed adolescents without PTSD left treatment
      sooner than the nonexposed. Need for attention to trauma in substance abuse
      treatment programs is discussed.

PMID- 15141785
TI  - Bringing order out of chaos: a culturally competent approach to managing the
      problems of refugees and victims of organized violence.
AB  - The collaborative program of the Transcultural Psychosocial Organization (TPO)
      provides a community-oriented and culturally sensitive public health response to
      the psychosocial problems of refugees and victims of organized violence. This
      paper describes the 9-step model that TPO has developed as a blueprint for each
      new intervention. Beneficiaries participate in determining priorities and there
      is an orientation toward culturally competent training, capacity-building, and
      sustainability. Two cases, one related to Sudanese refugees in Uganda and the
      other to internally displaced persons and returnees in postwar Cambodia, show how
      the TPO intervention protocol is adapted to local settings. The paper provides
      preliminary evaluative comments on the model's performance.

PMID- 15141786
TI  - Prevalence of posttraumatic stress disorder and comorbid depression in earthquake
      survivors in Turkey: an epidemiological study.
AB  - This study examined the prevalence of posttraumatic stress disorder (PTSD) and
      depression 14 months after the earthquake in Turkey in 2 randomly selected
      samples from the epicenter (n = 530) and a suburb of Istanbul 100 km from the
      epicenter (n = 420). The rates of PTSD and depression comorbid with PTSD were,
      respectively, 23 and 16% at the epicenter and 14 and 8% in Istanbul. The
      strongest predictor of traumatic stress symptoms was fear during the earthquake,
      whereas predictions with female gender, past psychiatric illness, damage to home,
      participation in rescue work, past trauma, and loss of close ones were
      significant but weak. Our findings suggest that devastating earthquakes have long
      term psychological effects. Psychological interventions reducing fear may improve
      PTSD in survivors.

PMID- 15141787
TI  - Treatment of posttraumatic stress disorder in postwar Kosovo high school students
      using mind-body skills groups: a pilot study.
AB  - This preliminary study examined whether the practice of mind-body techniques
      decreases symptoms of posttraumatic stress in adolescents. Posttraumatic Stress
      Reaction Index questionnaires were collected from 139 high school students in
      Kosovo who participated in a 6-week program that included meditation,
      biofeedback, drawings, autogenic training, guided imagery, genograms, movement,
      and breathing techniques. Three separate programs were held approximately 2
      months apart. There was no control group. Posttraumatic stress scores
      significantly decreased after participation in the programs. These scores
      remained decreased in the 2 groups that participated in the follow-up study when
      compared to pretest measures. These data indicate that mind-body skills groups
      were effective in reducing posttraumatic stress symptoms in war-traumatized high
      school students.

PMID- 15141788
TI  - Perceived social support and secondary traumatic stress symptoms in emergency
      responders.
AB  - This study investigated prevalence rates of secondary traumatic stress symptoms
      in Israeli Police forensic technicians, and the relationship between these
      symptoms and perceived social support as well as perceived severity of prior
      trauma (combat, work, personal). Ninety technicians from the Israeli Police
      Forensic Investigation Unit participated in the study. Intrusion and avoidance
      measured within the medium range of severity, whereas distress symptoms were
      below clinical threshold. Intrusion was significantly related to avoidance,
      distress, and the perceived severity of prior personal and work-related exposure.
      No significant relationship was found between perceived social support and
      secondary traumatic stress symptoms. The data suggest that this cohort utilized
      avoidance effectively as a defense against intrusion.

PMID- 15141789
TI  - Predictors of veterans' participation in cognitive-behavioral group treatment for
      PTSD.
AB  - Increasingly effective treatments for posttraumatic stress disorder (PTSD) have
      led to dramatic improvements in the lives of many trauma survivors; however, a
      significant subgroup of individuals with PTSD avoids mental health treatment.
      Little is known about the features distinguishing those who participate in
      treatment from those who do not. We analyzed archival clinical data from 197 male
      veterans who were evaluated in a Veterans Affairs Medical Center PTSD clinic. We
      found greater PTSD severity associated with initial enrollment and continued
      participation in a PTSD group treatment program, and we noted few differences on
      other background and symptom measures. These preliminary findings suggest
      possible directions for future research in this area, which may have implications
      for enhancing service delivery to individuals with PTSD.

PMID- 15141790
TI  - Twenty-four-hour ambulatory assessment of heart rate and blood pressure in
      chronic PTSD and non-PTSD veterans.
AB  - This study examined 24-hr levels of ambulatory heart rate (HR) and blood pressure
      (BP) in 2 groups of male veterans: 19 with chronic posttraumatic stress disorder
      (PTSD) and 17 who never met criteria for PTSD. The relationships between
      diagnostic status, basal cardiovascular activity, and cardiovascular reactivity
      to stress were examined. Hierarchical linear modeling analyses revealed that the
      PTSD group had higher resting HR than the non-PTSD group. Moreover, the PTSD
      group showed greater BP reactivity during times of affective distress than the
      non-PTSD group. The health care implications of these findings are discussed, as
      are directions for future research.

PMID- 15141791
TI  - Revictimization and interpersonal resource loss predicts PTSD among women in
      substance-use treatment.
AB  - Child physical abuse (CPA) and child sexual abuse (CSA) were hypothesized to be
      associated with revictimization and interpersonal resource loss in adulthood.
      These adulthood experiences were, in turn, hypothesized to increase risk for
      current posttraumatic stress disorder (PTSD). High-risk women were recruited from
      an innercity drug and alcohol treatment center (N = 105). Interpersonal resource
      losses, partner-produced physical assault, adulthood rape, CPA, and CSA had
      direct effects on PTSD. CPA and CSA also had indirect effects on PTSD through
      rape, which, in turn, predicted PTSD. Results suggest that the traumatic origins
      of current PTSD among substance-using women are multifaceted and support the
      importance of considering interpersonal coping resources in evaluating and
      treating female substance users.

PMID- 15141792
TI  - Management of septic shock: current concepts, with a particular emphasis on the
      role of source control, and future perspectives.
AB  - Sepsis is an infection-induced syndrome characterized by a generalized
      inflammatory state. The normal reaction to infection involves a series of complex
      immunological processes. A potent, complex immunological cascade ensures a prompt
      protective response to microbial invasion in human beings. Although activation of
      the immune system during microbial invasion is generally protective, septic shock
      develops in a number of patients as a consequence of excessive or poorly
      regulated immune response to the offending organism. This unbalanced reaction may
      harm the host through a maladaptive release of endogenously generated
      inflammatory compounds. Early recognition of the syndrome is of key importance to
      promptly start appropriate management. Timely, aggressive resuscitation to
      preserve organ function remains a fundamental principle in the care of septic
      patients. The specific treatment is directed at identifying and treating the
      underlying disorder. The physician should investigate diligently for the presence
      of active infection using modern imaging methods and other diagnostic studies to
      localize the site of infection and to obtain adequate culture specimens from
      potential infective sources. Early administration of appropriate, effective
      antibiotic therapy is important in the management of septic patients. Infected
      fluid collections and/or infected necrotic tissues should be drained or debrided
      without delay. Adequate nutritional support is indicated in the management of the
      septic patient. A number of adjuvant therapies, aimed at blunting/downregulating
      the host immune response to bacterial infection are currently under intensive
      investigation; however, the complexity of immunological defences and the
      potential for complementary interaction of the different components of the
      inflammatory cascade make the development of these pharmacological interventions
      difficult.

PMID- 15141793
TI  - Airway management by first responders when using a bag-valve device and two
      oxygen-driven resuscitators in 104 patients.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the capability of first responders to
      ensure an airway and ventilate the lungs of a patient employing a bag-valve
      device and two oxygen-driven resuscitators. METHODS: Prospective, controlled,
      blinded, single-centre clinical trial using a bag-valve device and one of two FR
      300 devices, with 20 cmH2O working pressure, flows of 24 and 30 L min(-1). One
      hundred-and-four patients were analysed. Induction of anaesthesia was followed by
      ventilation of the lungs with a bag-valve device and an Oxylator (CPR Medical
      Devices Corp., Markham, Ontario, Canada) in manual and automatic modes. Each
      series was repeated twice by a fireman first responder using a hand-held mask to
      seal the airway, once under anaesthesia and then again under anaesthesia with
      muscle relaxation. RESULTS: Patients' mean age 49 +/- 17 yr; 47% male, 48-132 kg.
      Only 29% had optimal facial and airway physiognomy. Airway management was
      significantly poorer when the bag-valve device was used than with either Oxylator
      mode (P < 0.0001); 23% of cases were not manageable with the bag-valve device.
      Gastric insufflation was markedly less with the Oxylator (P < 0.02). CONCLUSIONS:
      The use of an oxygen-driven device improves the ability of first responders to
      secure an airway and reduce gastric insufflation, even when distracted. Oxylators
      perform significantly better (P < 0.0001) than the bag-valve device.

PMID- 15141794
TI  - Can first responders achieve and maintain normocapnia when sequentially
      ventilating with a bag-valve device and two oxygen-driven resuscitators? A
      controlled clinical trial in 104 patients.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the capability of first responders to
      achieve and maintain normal ventilation of the lungs of victims employing a bag
      valve device and two oxygen-driven resuscitators. METHODS: Prospective,
      controlled, blinded, single-centre clinical trial using a bag-valve device and
      one of two FR-300 devices, with 20 cmH2O working pressure, and flows of either 24
      or 30 L min(-1). One hundred and four patients were analysed. Induction of
      anaesthesia followed by ventilation of the lungs with a bag-valve device and an
      Oxylator in manual and automatic modes performed by a fireman first responder.
      Each series was repeated for three conditions (anaesthesia; anaesthesia plus
      muscle relaxation, both with facemask; anaesthesia plus relaxation using an
      endotracheal tube). RESULTS: Patients age 49 +/- 17 yr; 47% males, 48-132 kg.
      Normocapnia was achieved and maintained in 66% (bag-valve device), 82%
      (Oxylator). CONCLUSIONS: The use of an oxygen-driven device improves the ability
      of first responders to achieve and maintain normocapnia even when distracted. Use
      of the Oxylators improves performance (P < 0.001) vs. the bag-valve device
      significantly.

PMID- 15141795
TI  - No difference in electroencephalographic power spectra or sensory-evoked
      potentials in patients anaesthetized with desflurane or sevoflurane.
AB  - BACKGROUND AND OBJECTIVE: Hitherto, neither desflurane nor sevoflurane, with
      similar physicochemical properties, have been compared with regard to their
      effects on the central nervous system. We compared the effects of desflurane and
      sevoflurane on electrical cortical activity and sensory transmission at two
      anaesthetic concentrations in patients undergoing hysterectomy. METHODS: The 1
      and 2 MAC in nitrous oxide/oxygen (55%/45%) of desflurane or sevoflurane were
      administered while electroencephalographic power spectra and the somatosensory
      evoked potentials were measured and correlated with cardiovascular effects.
      RESULTS: Both volatile agents induced a concentration-related increase of power
      in the slow delta-band and a concomitant decrease of power in the fast beta
      domain. There was a close correlation with regard to the decrease in beta-power
      and heart rate (r2 = 0.988) and systolic blood pressure (r2 = 0.952) following
      both agents. Desflurane and sevoflurane had little effect on the early N20-peak,
      but affected the late N100-peak. There was a concentration-related increase in
      latency and a depression of amplitude height. Changes were not significantly
      different between both agents. CONCLUSIONS: Both desflurane and sevoflurane
      possess a similar profile with regard to their hypnotic effects and a similar
      outline in depressing propagation within the sensory nervous system. Cortical
      nervous effects are mirrored closely in heart rate and systolic blood pressure.

PMID- 15141796
TI  - Unplanned hospital admission in children undergoing day-case surgery.
AB  - BACKGROUND AND OBJECTIVE: Unplanned hospital admission is a measure of quality of
      care in the setting of day-case surgery. We set out to identify the incidence and
      causes of unplanned hospital admission in a paediatric day-case unit. METHODS: A
      retrospective survey to determine the incidence and causes of unplanned hospital
      admissions in children undergoing day-case surgery. The survey covered the period
      from January 1996 until December 1999 inclusive in a university affiliated
      children's hospital. This hospital is the second largest paediatric referral
      centre in Ireland with total admissions across all specialities during the study
      period of 42 738. RESULTS: During the study period 10 772 children underwent day
      case surgery, of whom 242 (2.2%) experienced unplanned hospital admission. The
      reasons for admission were surgical 146 (54%), anaesthetic 44 (16%), social 38
      (14%), medical 31 (11%) and unclassified 10 (4%). Pain, surgical complications
      and/or further management, admission for observation, extensive surgery and
      oozing were the commonest surgical reasons. Postoperative nausea and vomiting,
      anaesthetic-related complication and somnolence were the commonest anaesthetic
      causes responsible for admission. Surgery performed after 15:00 h was an
      important factor associated with admission for social reasons. Orthopaedic
      surgery accounted for the largest absolute number of unplanned admissions with 61
      (25%), followed by urology with 46 (19%) and general surgery with 46 (19%).
      However, measured as percentage of caseload, urology had the highest proportion
      of unplanned hospital admissions. CONCLUSION: This study demonstrated that the
      incidence and causes of unplanned hospital admission following day-case surgery
      in children are similar to those for adults.

PMID- 15141797
TI  - Can we rely on arterial line sampling in performing activated plasma
      thromboplastin time after cardiac surgery?
AB  - BACKGROUND AND OBJECTIVE: Arterial catheters are routinely used to sample blood
      for clotting studies in most cardiothoracic intensive care units. The clotting
      profile in surgical bleeding after cardiac surgery influences further management.
      Aspiration and discard of a certain amount of blood from the line, prior to
      sampling, are assumed to clear heparin contamination. We have investigated this
      assumption through analysis of the clotting profile by simultaneous arterial line
      and peripheral venous samples. METHODS: The morning following cardiac surgery,
      simultaneous arterial line and peripheral venous blood samples were taken for
      activated plasma thromboplastin time (APTT) ratio and international normalized
      ratio (INR) in 49 randomly selected patients. Also, a thromboelastogram analysis
      (TEG) (n = 7) was made. A survey of 22 UK cardiothoracic intensive care units was
      carried out to determine the practice for the withdrawal of blood for clotting
      studies. RESULTS: The median arterial APTT ratio value was 1.32 +/- 0.52 as
      compared to the median peripheral APTT ratio value which was 1.1 +/- 0.24 (P <
      0.001). INR values were statistically similar by both routes. Heparin
      contamination was confirmed by TEG which revealed that the R-value for arterial
      catheter blood samples without heparinase in the cup was higher (406.00 +/- 64.44
      s) compared with the value for arterial samples with heparinase in the cup
      (318.28 +/- 47.26s, P < 0.05). The survey of 22 UK cardiothoracic intensive care
      units showed that heparinized arterial lines were by far the commonest ports used
      for blood withdrawal for the measurement of APTT ratio results. CONCLUSIONS:
      Samples withdrawn from heparinized arterial lines cannot be relied upon for APTT
      ratio results.

PMID- 15141799
TI  - The recruitment of EEA and non-EEA doctors to Specialist Registrar posts in
      anaesthesia in the Wessex Region of the UK: a retrospective study of factors
      influencing successful appointment.
AB  - BACKGROUND AND OBJECTIVE: A retrospective analysis of applicants to Specialist
      Registrar training posts in anaesthesia in the Wessex Region of the UK was
      undertaken. METHODS: Applicants whose primary medical qualification was obtained
      in the European Economic Area were compared to applicants whose primary medical
      qualification was obtained outside it. The time since qualification, the time
      spent in anaesthesia, the time spent in other specialities, the post currently
      held and the success of the application were recorded. RESULTS: For doctors with
      a primary medical qualification from outside the European Economic Area, the
      median time since obtaining that qualification was 12.0 yr compared with 6.0 yr
      for doctors qualifying within it (P = 0.0001, U-test). Thirteen out of 89 (15%)
      doctors whose primary medical qualification was from outside the European
      Economic Area and 39 out of 61 (64%) doctors whose primary medical qualification
      was from within it were shortlisted for interview (P = 0.0001, chi2-test). Six
      out of 13 (46%) shortlisted doctors from outside the European Economic Area were
      appointed at interview compared with 24 out of 39 (62%) shortlisted doctors who
      qualified within it (P = 0.33, chi2-test). CONCLUSIONS: In the Wessex Region of
      the UK, applicants whose primary medical qualification is obtained within the
      European Economic Area are approximately four times as likely to be shortlisted
      than doctors qualifying outside it. However, after shortlisting, both categories
      are equally likely to be successful at interview.

PMID- 15141798
TI  - A prospective, randomized, blind comparison between saline, calcium gluconate and
      diphoterine for washing skin acid injuries in rats: effects on substance P and
      beta-endorphin release.
AB  - BACKGROUND AND OBJECTIVE: A randomized, blind study to evaluate the effects on
      beta-endorphin and substance P release after washing acid burns with 0.9% saline,
      calcium gluconate or diphoterine in a model of chemical burn in rats. METHODS:
      Twenty Sprague-Dawley rats (approximate weight 250 g) were anaesthetized with
      ketamine (30 mg kg(-1) intramuscularly) and then given an acid injury on the back
      skin with 0.5 mL of hydrochloric acid 52%. The rats were then randomly allocated
      to receive no washing (control group, n = 5), washing with normal saline (0.9%
      NaCl) (n = 5), 10% calcium gluconate (n = 5) or diphoterine (n = 5). Blood
      concentrations of substance P and beta-endorphin were measured 6 h, 48 h and 7
      days after the chemical burn. An independent blinded observer evaluated wound
      healing at the 7th day. RESULTS: Seven days after burn wound healing was almost
      complete only in rats treated with diphoterine. Plasma concentrations of
      substance P were lower in rats receiving skin flushing with diphoterine compared
      to the other groups at 6 and 48 h after acid burn (P < 0.05 and P < 0.05,
      respectively); this was also associated with higher concentrations of beta
      endorphin at day 7 (P < 0.05). CONCLUSIONS: Skin flushing with diphoterine
      reduced substance P release during the first 48 h after burn, and was associated
      with better wound healing and higher concentrations of beta-endorphin 7 days
      later when compared with normal saline or 10% calcium gluconate.

PMID- 15141800
TI  - Demography of French anaesthesiologists. Results of a national survey by the
      French College of Anaesthesiologists (CFAR) and the French National Society of
      Anaesthesia and Intensive Care (SFAR), supported by the National Institute for
      Demographic Studies (INED).
AB  - BACKGROUND AND OBJECTIVE: The perception of a looming manpower shortage led the
      French College of Anaesthesiologists (CFAR) and the French Society of Anaesthesia
      and Intensive Care (SFAR), with assistance from the National Institute for
      Demographic Studies (INED), to conduct a national survey of French
      anaesthesiologists in order to determine precise physician characteristics data,
      analyse professional practices and project future service provision. METHODS: The
      survey was based on self-administered individual questionnaires, approved by the
      National Committee on Informatics and Freedom (CNIL). The survey was carried out
      at the end of 1998 among 1484 hospitals (590 public and 894 private), under the
      supervision of local referees and regional co-ordinators. RESULTS: Of 9741
      anaesthesiologists' posts, 5694 (58%) are in public hospitals, 3569 (37%) in
      private practice and 478 (5%) in private hospitals within the National Health
      Service, i.e. the participant au service public hospitalier (PSPH). Complex
      validation of the results was necessary to account for the missing responses and
      multiple sites of activity. The survey identified 8876 specialists practising
      anaesthesia and intensive care in France at the beginning of 1999, including 216
      in French overseas territories. This figure is consistent with that published by
      the Medical Council (Ordre des Medecins) on 1 January 1999, identifying 8950
      anaesthesiologists in France, including 234 in the overseas territories. Annual
      growth in the anaesthesiologist population has fallen from 9% pre-1989 to 0% in
      1999. Male anaesthesiologists outnumber females (35.7%). The average age has
      risen from 42.8 yr in 1989 to 45.9yr in 1999. The age distribution of
      anaesthesiologists has become bell shaped, reflecting reduced numbers of younger
      practitioners. There are currently 14.75 anaesthesiologists per 100 000 people
      (compared to 12.9 in 1989), a figure slightly above the European average, but
      there is considerable geographical inequality between the north and south of
      France, with increased concentrations in large cities that contain university
      hospitals. CONCLUSIONS: Future service provision must take account of falling
      numbers of new anaesthesiologists and an increase in retirements, but must also
      include changes in working practices, such as the European Working Time
      Directive. If anaesthesia manpower shortages are to be avoided, there must be a
      restructuring of the work-place, a redefinition of tasks and improved management
      of working time.

PMID- 15141802
TI  - Perioperative blood loss and transfusion requirements in patients with fractured
      neck of femur.

PMID- 15141801
TI  - Bolus application of remifentanil with propofol for dilatation and curettage.
AB  - BACKGROUND AND OBJECTIVE: This study was designed to determine which single bolus
      dose of remifentanil in combination with propofol and nitrous oxide is best to
      control the haemodynamic, autonomous and somatic responses in patients scheduled
      for dilatation and curettage of the uterine cervix. We evaluated the adequacy of
      different bolus doses of remifentanil, associated with propofol and nitrous
      oxide, for dilatation and curettage in a prospective double-blind study. METHODS:
      After institutional approval and informed consent, 34 healthy females undergoing
      curettage to remove material from the uterus after spontaneous abortion were
      randomized to receive remifentanil 0.5 microg kg(-1) intravenously (i.v.) (Group
      A; n = 4), 1 microg kg(-1) i.v. (Group B; n = 15) or 1.5 microg kg(-1) i.v.
      (Group C; n = 15), with propofol 2 mg kg (-1) i.v. in all groups. Anaesthesia was
      maintained with 60% nitrous oxide in oxygen. Haemodynamic, somatic and autonomic
      signs of light anaesthesia were registered to assess the response to surgical
      stress. Recovery times and Aldrete score were recorded at the end of the
      procedure. RESULTS: The groups were similar with regard to biometric data and
      duration of surgery. The poor results using the lowest dose of remifentanil
      obliged us to abandon this dose. The total dose of remifentanil was larger in
      Group C (100 +/- 5.7 microg vs. 65 +/- 4.1 microg in Group B; P < 0.05), but more
      patients required extra bolus injections in Group B (69% vs. 38% in Group C; P <
      0.01). Recovery times were significantly shorter in Group C. Aldrete scores when
      leaving the operation room was similar. CONCLUSIONS: Remifentanil 1.5 microg kg(
      1) i.v. with propofol 2 mg kg(-1) i.v. and 60% nitrous oxide in oxygen provided
      the best anaesthetic control with the fastest recovery times.

PMID- 15141803
TI  - Effect of preoperative discontinuation of antipsychotics in schizophrenic
      patients on outcome during and after anaesthesia.

PMID- 15141804
TI  - Postoperative adrenal crisis in a patient with Schmidt syndrome (autoimmune
      polyglandular endocrinopathy type II).

PMID- 15141805
TI  - One-lung ventilation, partial bypass and totally endoscopic CABG.

PMID- 15141806
TI  - Anaesthesia for Homans' procedure.

PMID- 15141807
TI  - The effect of meloxicam and deendothelisation on vascular responses in the rabbit
      renal and ear arteries.
AB  - BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is
      frequently limited by adverse effects resulting from the disruption of
      homeostatic functions of prostaglandins. OBJECTIVES: This study was aimed at the
      evaluation of the effect of selective COX-2 inhibitor meloxicam on
      vasoconstrictor responses to noradrenaline (NA) in rabbit renal artery chosen as
      a model vessel and in rabbit ear artery as a peripheral artery under in vitro
      conditions. METHODS: Rabbit renal and ear arteries were perfused at constant
      flow. Vascular responses to NA before and after meloxicam administration and
      after deendothelisation by air bubbles were measured and registered as changes in
      perfusion pressure. RESULTS: It was found out that vasoconstrictor responses to
      noradrenaline when exposed to meloxicam were not enhanced significantly in both
      arterial preparations. Deendothelisation itself did not increase responses
      affected by meloxicam in the renal and ear arteries but in comparison with
      control groups the responses were significantly augmented, especially in the ear
      artery. CONCLUSIONS: The results obtained in this study demonstrate that
      meloxicam had not affected adversely the vasoconstrictor activity in different
      types of vessels without selectivity on vascular beds. Endothelial removal
      potentiated vasoconstrictor responses in arteries pre-treated by meloxicam when
      compared with intact vessels. (Tab. 2, Fig. 4, Ref. 19.)

PMID- 15141808
TI  - Endoscopic cure of cerebellar hemangioblastoma.
AB  - This is the first report of a purely endoscopic cure of the cerebellar cystic
      hemangioblastoma in a 28-year-old with an unfavourable location of the vascular
      node in the proximity of brainstem structures. A complete excision of the lesion
      was achieved by means of endoscopy without any violation of the subarachnoidal
      space, so that a complete cyst regression was observed on CT follow-up
      investigations. (Fig. 5, Ref. 8.)

PMID- 15141809
TI  - Complex therapy of advanced colorectal carcinoma.
AB  - The present paper reports on a complex therapy of 18 patients with primary
      unresectable advanced carcinoma of the rectum and rectosigmoid. The results of
      surgery following complete chemoradiotherapy are evaluated. Radical surgery was
      successful in 15/18 patients. The authors describe a high incidence of
      postoperative complications and point out a high erudition of an oncosurgeon
      necessary for such intervention as well as for the indication of a patient to
      this extensive operation. (Tab. 2, Ref. 18.)

PMID- 15141810
TI  - Acute toxicity of propafenone in a case of suicidal attempt.
AB  - We describe a successful treatment of 28-year old man who ingested in a suicidal
      attempt up to 30 pills each containing 150 mg (4500 mg) of propafenone. Results
      of clinical toxicology were obtained with high performance liquid chromatography
      from the urine sample. Semiquantitative analysis has shown a high peak for
      propafenone hydrochloride. The main clinical findings were coma, hypotension,
      acidosis, sinoatrial block, junctional tachycardia and ventricular arrhythmias
      necessitating defibrillation. Maximum occurence of arrhythmias was observed 2.5
      hours after hospital admission, while the cessation of toxic signs started 4.5
      hours later. Gastric lavage, arteficial ventilation, administration of
      alkalinization solutions and management of rhythm disorders were the most
      important therapeutic measures in this case. (Fig. 2, Ref. 18.)

PMID- 15141811
TI  - Monitoring of selected "non-hepatic" laboratory parameters in hospitalized
      cirrhotic patients and their influence on prognosis.
AB  - AIM OF THE STUDY: To evaluate the prognostic importance of the analysis of
      leucocytes, prothrombin time and selected serum biochemical parameters in
      hospitalized patients with liver cirrhosis. PATIENTS AND METHODS: At the
      Intensive Metabolic Care Unit of 1st Department of Internal Medicine we evaluated
      150 patients (87 males, 63 females) with liver cirrhosis at average age: 52.51 +/
      7.99 years, Child-Pugh score: 11.34 +/- 2.99. 47 patients have died during
      hospitalization, 103 patients have improved. Student t-test was used for
      statistical analysis. RESULTS: Patients who expired had higher serum leucocyte
      levels and lower prothrombin time and natriuresis when compared with survivors.
      Low serum sodium levels, hyperkalemia, decompensated metabolic acidosis,
      spontaneous hypoglycemia, DIC and renal failure occured more often in the
      patients with liver cirrhosis who died during hospitalisation. CONCLUSION:
      Hematological abnmormalities and acid base disturbance are associated with higher
      hospital mortality rate in patients with liver cirrhosis. (Tab. 6, Ref. 20.)

PMID- 15141812
TI  - History and the roots of angiology.
AB  - The authors present a short historical view of the origin of anatomic terms of
      some arteries and veins. By analysing the historic anatomic terminology the
      authors point out that various developmental stages of anatomy had an impact on
      anatomic language. During the formation of particular terms, instead of prefering
      the classical languages of Latin and Greek, some terms originated from other
      languages and have remained in terminology that is used today. (Ref. 7.)

PMID- 15141814
TI  - Treatment trends in anal fissures.
AB  - BACKGROUND: Conservative treatment of anal fisures are reserved for acute forms.
      Many different treatments are available for chronic anal fissures, which offer
      different responses and risks for complications. MATERIALS AND METHODS: This
      study describes various surgical and non-surgical treatment modalities offered
      for chronic anal fissure with their advantages and complications. CONCLUSION:
      Considering the various pros and cons, we are of the opinion that treatment of
      chronic anal fissure must be individualized, depending on the clinical condition
      of patients. Explaining all the available options to the patient, the clinician
      should suggest a good and safe choice to achieve the optimum results for the
      particular patient. (Tab. 2, Ref. 26.)

PMID- 15141813
TI  - Student scientific activities at Jessenius Faculty of Medicine, Comenius
      University in Martin--current state and its future.
AB  - AIM: The purpose of this study was to assess the history and the current state of
      Student Scientific Activities (SSA) at Jessenius Faculty of Medicine, Comenius
      University in Martin (JFM CU) and outline its future heading. METHODS: An
      anonymous questionnaire was used to ascertain the current involvement of students
      in SSA at JFM CU. The number and affiliation of students, participating at the
      annual Student Scientific Conference (SSC), to individual medicine fields were
      examined retrospectively. RESULTS: After partial down-fall of SSA at JFM CU in
      1990-1996, at annual SSC in 1997 nine papers were presented. The number of
      presenting students in the following years was: 7 students in 1998, 6 in 2000, 16
      in 2001, 25 in 2002, and 35 in 2003 with proportional representation of pre
      clinical and clinical departments. In SSA at JFM CU Slovak medical students are
      predominantly involved, while only few foreign students were interested in SSA
      (1997--2, 1998--1, 2002--1). Similar situation was observed in students of
      Nursing, where only seven students presented their research results (1997--1,
      2000--1, 2003--5) in the history of SSC. CONCLUSION: Results of the study showed
      that the number of students participating at annual SSC is increasing. Since the
      involvement of students as well as tutors in SSA is influenced by many factors,
      the main task in the future is to eliminate the negative and to promote the
      positive ones. (Tab. 4, Fig. 3, Ref. 11.)

PMID- 15141815
TI  - Growing pains.

PMID- 15141816
TI  - Healthy Vision Month--May 2004: focus is on diabetic retinopathy.

PMID- 15141817
TI  - Dr. Sheedy's article on PALs.

PMID- 15141818
TI  - Fingernails hide organisms.

PMID- 15141819
TI  - Optic disk evaluation and utility of high-tech devices in the assessment of
      glaucoma.
AB  - BACKGROUND: Every clinician has at one time or another examined a patient who was
      misdiagnosed as having glaucoma or whose diagnosis of glaucoma was missed.
      Although glaucoma can exist with normal intraocular pressures, clinicians often
      rely on the presence of visual-field defects and the degree of optic disk cupping
      to direct care. However, assessment of cupping is but one small part of optic
      disk evaluation in glaucoma, and other features of the optic nerve head and
      retinal nerve fiber layer must be closely inspected to help diagnose borderline
      cases. In addition, glaucoma can exist without visual-field loss. High-tech
      devices offer an added dimension in the objective assessment of structure when
      subjective tests of function and/or ophthalmoscopic observations are equivocal.
      METHODS: This article details the various parameters of optic disk and retinal
      nerve fiber layer evaluation and their significance in the assessment of
      glaucoma. In addition, the role of four high-tech devices is evaluated for their
      utility in the assessment and progression of glaucomatous damage. CONCLUSIONS:
      When one attempts to classify a patient as having glaucoma, the degree of cupping
      and the presence or absence of visual field loss can be misleading. Prior to
      definitive diagnosis, a thorough evaluation of the optic disk and retinal nerve
      fiber layer, and appropriate use of high-tech devices, should help reduce the
      under-diagnosis and overdiagnosis of this disease.

PMID- 15141820
TI  - Presumed ocular sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown
      etiology. Ocular manifestations commonly occur in patients with sarcoidosis, with
      a granulomatous anterior uveitis as the most-prevalent ocular sign. Acute
      symptoms of uveitis, such as pain, photophobia, lacrimation, or redness, may be
      absent. Without early detection and timely treatment, this "silent uveitis" may
      cause permanent ocular damage. CASE REPORTS: Two patients came in for routine eye
      examinations, with no symptoms of anterior uveitis. The first, a 36-year-old man,
      had a bilateral granulomatous anterior uveitis. The uveitis was treated with
      topical corticosteroids, with no complications. The second case involved a 44
      year-old woman with chronic, recurrent, bilateral, non-granulomatous anterior
      uveitis. Despite treatment with topical and oral corticosteroids. the patient had
      a prolonged course with recurrent episodes leading to secondary sequelae,
      including glaucoma and cataract. Both patients were co-managed with internal
      medicine, and in each case, systemic workups were consistent with sarcoidosis.
      CONCLUSION: Anterior uveitis often manifests as the initial presentation of
      sarcoidosis. Without acute symptoms, the detection and diagnosis may be delayed,
      leading to visual deterioration. The diagnosis of sarcoidosis may be difficult,
      owing to the lack of definitive diagnostic criteria and a variety of
      presentations. Histologic confirmation may not always be possible or practical.
      However, a range of serological and radiological tests, when combined with
      physical and ophthalmic evaluation, can lead to the presumed diagnosis of
      sarcoidosis. Aggressive treatment is imperative in order to prevent permanent
      structural damage to the eye resulting from this idiopathic inflammation.

PMID- 15141821
TI  - A primer for the optometric management of unilateral spatial inattention.
AB  - BACKGROUND: Unilateral spatial inattention (USI) (a.k.a. neglect, unilateral
      neglect, visual neglect) is a common occurrence after stroke. It can also occur
      subsequent to traumatic brain injury. Insult to the right inferior (posterior)
      parietal cortex is the structure that is virtually always involved, although
      other brain areas have been implicated. The major consequence of USI is that the
      patient is unaware of one side of the body, and/or one side of visual space.
      Current literature expresses this as USI in the individual's personal, peri
      personal, and extra-personal spaces. METHODS: We discuss the condition's natural
      history, occurrence and behavioral consequences. CONCLUSIONS: We propose a system
      for the optometric management of USI in extra-personal and peri-personal spaces.

PMID- 15141822
TI  - Putting it all together and entering practice.

PMID- 15141823
TI  - Managing the marketing effort.

PMID- 15141824
TI  - HIPAA and the FCLCA.

PMID- 15141825
TI  - CMS now posting Medicare policy changes online with Medlearn Matters.

PMID- 15141826
TI  - Endotoxin stress responses in chickens from different genetic lines. 1. Sickness,
      behavioral, and physical responses.
AB  - Genetic variation in response to lipopolysaccharide (LPS) challenge was studied
      in chicken lines divergently selected for high (HGPS) and low (LGPS) group
      productivity and survivability resulting from cannibalism and flightiness in
      colony cages and in a Dekalb XL (DXL) commercial line. Six-week-old chicks were
      randomly assigned to control or experimental groups and were injected
      intravenously with Escherichia coli LPS (5 mg/kg of BW) or distilled saline
      (control). Sickness responses were measured at 6, 12, 24, 48, and 72 h following
      injection (n = 10 at each point in time for each line). Although LPS induced
      widespread sickness symptoms in all of the treated chicks, the reactions were in
      a genotypic- and phenotypic-specific manner. Compared with LGPS and DXL chicks,
      HGPS chicks had acute, transient behavioral and physical changes with less effect
      on BW gain, organ development, and core temperature, which were in the order HGPS
      < DXL < LGPS. The effects of heritable factors and LPS challenge on the
      differential responses among the present lines may reflect each line's unique
      adaptability to stress and resistance to infection and inflammation. The results
      suggested that the present chicken lines may provide a valuable animal model for
      investigating the effects of genetic-environmental interactions on the behavioral
      and physiological homeostasis in response to stress and disease.

PMID- 15141827
TI  - Performance characteristics and economic comparison of broiler chickens fed wheat
      and triticale-based diets.
AB  - The effects of triticale and wheat on broiler (mixed sexes) performance and cost
      of production were compared. In experiment 1, wheat- and triticale-based diets
      were fed to 3 strains of broilers (Ross x Ross, Hubbard x Hubbard, and Ross x
      Hubbard). Each of the diets was provided to 5 cages/strain (n = 10 chicks/cage;
      1,273 cm2/bird). Weekly BW, gain, feed consumption, and feed conversion ratio
      (FCR; g of feed/g of gain) were determined. At 42 d, 4 chicks/pen were shipped to
      a commercial processing plant. The plucked, eviscerated carcasses were evaluated
      for carcass traits. Overall, the triticale-fed birds had lower final BW and
      average daily gain and higher FCR. Eviscerated carcass, thigh, and drum weights
      were lower, but pectoralis minor as a percentage of carcass weight was greater in
      triticale-fed birds. In experiment 2, a wheat diet and a diet in which triticale
      was substituted (by weight) for wheat were provided in a 3-phase feeding program.
      Each diet was provided to 2 identically-equipped commercial barns housing 17,034
      broilers each. Individual BW of a sample of birds were recorded in each barn at
      0, 19, 34, and 42 d, corresponding to the beginning and end of each dietary
      phase. Feed consumption and FCR were calculated for each barn. An analysis of
      each of the diets was calculated using a broiler chicken production cost model.
      Final BW, feed consumption, carcass weight at processing, flock uniformity,
      percentage of Grade A carcasses, and percentage of condemned carcasses were not
      affected by cereal source. Overall FCR (2.165, 2.036; P = 0.0052), feed cost
      (dollars 0.617, dollars 0.577/kg live weight; P = 0.0260), and total cost of
      production (dollars 1.019, dollars 0.972/kg live weight; P = 0.0183) were greater
      for the triticale than wheat diets, respectively. Triticale would be an
      economically feasible replacement for wheat in broiler diets when its price is
      less than or equal to 95% of the cost of wheat, less dollars 18 (Canadian).
      Increased knowledge of the available nutrient profile of triticale, as well as
      least-cost feed formulation would likely increase the value of triticale relative
      to wheat for broilers.

PMID- 15141828
TI  - Influence of hard water on the bioavailability of enrofloxacin in broilers.
AB  - To define the impact that use of different levels of hard water has on the
      bioavailability of the antibacterial, enrofloxacin, in poultry, an oral
      bioavailability-pharmacokinetic study of the drug was carried out. Two hundred
      fifty clinically healthy broilers, divided into 5 groups, were individually dosed
      orally with 10 mg/kg of enrofloxacin diluted to 0.1%. The enrofloxacin was
      diluted with water of increasing hardness in accordance with an international
      grading system. After dosing, blood samples were obtained at predetermined times.
      Serum was recovered and quantified for enrofloxacin by means of an agar diffusion
      bacteriological method. The composite serum concentrations of enrofloxacin and
      metabolites vs. time relationships were analyzed using software for compartmental
      pharmacokinetics. Results show that there were statistically significant
      differences in the following pharmacokinetic variables: maximal serum
      concentrations (Csmax), area under the time vs. concentration curves, and half
      lives of the elimination phases. The means of these values showed a linear decay
      of Csmax from one group to the next as water hardness increased. Chemical
      analysis of water calcium and magnesium ions revealed the formation of
      coordination groups. Lack of interference with the microbiological activity in
      vitro of enrofloxacin diluted in hard water indicated that diminished absorption
      may be partly responsible for reduction in bioavailability. These results stress
      the need for proper water supply when enrofloxacin is used and point out a factor
      that must be taken into account when clinical outcomes do not comply with
      expectations.

PMID- 15141829
TI  - Sodium chloride-induced acute and chronic pulmonary hypertension syndrome in
      broiler chickens.
AB  - Two hundred forty 1-d-old Arbor Acres commercial broiler chicks were divided into
      control and experimental (T1 and T2) groups that, between 8 and 42 d of age, were
      provided drinking water containing 0, 600, or 1,200 mg/L sodium from sodium
      chloride, respectively. The pulmonary hypertension syndrome (PHS) incidence and
      the right to total ventricle weight ratio (RV/ TV) were calculated weekly, and
      blood samples and lung tissues were collected weekly from 10 birds per group to
      evaluate the structural and hemodynamic characteristics of pulmonary vessels.
      Saline drinking water significantly increased the incidence of PHS and RV/TV
      ratios. In the T2 group the PHS mortality exhibited 2 peaks, including an acute
      peak from 14 to 21 d of age and a chronic peak from 35 to 42 d of age. During the
      acute peak of PHS mortality the blood volume (BV), filtration index (FI), and
      packed cell volume (PCV) increased in groups T1 and T2 when compared with the
      control group. During the acute peak there were no differences among groups in
      the ratio of wall to total area (WA/TA), medial thickness of pulmonary arteriole
      walls (mMTPA), the percentage of thick-walled peripheral lung vessels (%TWPV),
      the percentage of muscular arterioles (%MA), or the percentage of nonmuscular
      arterioles (%NMA) in pulmonary arterioles. During the chronic peak of PHS
      mortality, group T2 exhibited the highest values for %TWPV, %MA, WA/TA, and mMTPA
      and the lowest values for %NMA when compared with the T1 and control groups. Also
      during the chronic peak the groups did not differ in BV or FI, whereas PCV
      remained elevated above control values in groups T1 and T2. These observations
      indicate that hemodynamic changes related to viscous resistance to blood flow
      (BV, FI, PCV) predominated throughout the acute peak of PHS mortality, whereas,
      during the chronic stages of PHS mortality, increased vascular resistance to
      blood flow also was imposed by remodeling of the pulmonary vasculature.

PMID- 15141830
TI  - Aflatoxin-induced toxicity and depletion of hepatic vitamin A in young broiler
      chicks: protection of chicks in the presence of low levels of NovaSil PLUS in the
      diet.
AB  - Aflatoxin contamination of foods and livestock feeds is an ongoing problem. In
      this research, NovaSil PLUS (NSP), a calcium montmorillonite clay that is
      commonly used as an anticaking agent in feeds, was evaluated for its ability to
      bind aflatoxin B1 (AfB1) in vitro and to prevent the onset of aflatoxicosis and
      vitamin A depletion in broiler chicks in vivo. Isothermal analyses were conducted
      with NSP and AfB1 to quantitate and characterize critical sorption parameters at
      equilibrium, i.e., ligand saturation capacities, affinity constants, and
      thermodynamics of the sorption process. In vitro results indicated that AfB1 was
      tightly sorbed onto the surface of NSP, which provided a high capacity and high
      affinity for the ligand. Thermodynamics favored sorption of AfB1 to NSP. The
      process was exothermic and spontaneous with a mean heat of sorption equal to
      approximately -50 kJ/mol, suggesting chemisorption (or tight binding). In
      addition to the in vitro studies, the effectiveness of NSP as an aflatoxin
      enterosorbent to attenuate the onset of aflatoxicosis in broiler chicks was
      determined at 3 different inclusion levels in the diet (0.5, 0.25, and 0.125%).
      NSP alone was not toxic to chicks at a level as high as 0.5% in the total diets
      (based on body and organ weights, feed intake, and hepatic vitamin A levels). NSP
      in the diet significantly protected chicks from the effects of highlevel exposure
      to aflatoxins (i.e., 5 mg/kg) and preserved hepatic vitamin A levels, even at
      lower dietary intake of clay.

PMID- 15141831
TI  - Further evaluation of nonfeed removal methods for molting programs.
AB  - The objective of this study was to evaluate several nonfeed removal methods
      compared with feed removal for induced molting of laying hens. An experiment was
      conducted using 576 Dekalb White hens (69 wk of age) randomly assigned to 1 of 8
      dietary treatments. Two of these treatments consisted of feed removal for 10 d
      followed by ad libitum access to a 16% CP, corn-soybean meal diet or a 94% corn
      diet for 18 d. The other 6 treatments provided ad libitum access for 28 d to
      diets containing 94% corn, 94% wheat middlings (WM), 71% WM: 23% corn, 47% WM:
      47% corn, 95% corn gluten feed, and 94% distillers dried grains with solubles
      (DDGS). At 28 d, all hens were fed a laying hen diet (16% CP), and production
      performance was measured for 40 wk. The 2 feed removal treatments resulted in
      total cessation of egg production within 6 d. Egg production of hens fed the 94%
      WM, 71% WM: 23% corn, corn, corn gluten feed, and 47% WM: 47% corn diets all
      decreased to 6% or less by d 12, 16, 19, 20, and 28, respectively. Egg production
      of hens fed DDGS never decreased below 18%. Body weight loss ranged from 10%
      (DDGS) to 26% (10-d feed removal), with the other treatments being similar at
      17%. No consistent differences were observed among treatments throughout the 40
      wk postmolt period for egg production, egg specific gravity, egg weight, egg
      yield, or feed efficiency. No differences were observed among feed removal
      treatments versus several nonfeed removal treatments for ovary and oviduct
      weights and blood heterophil:lymphocyte ratios during the molt period. In
      addition, interactive social behaviors were not different throughout the molt
      period between hens fed the 94% WM and those deprived of feed for 10 d. Our
      results indicate feeding WM, corn, corn gluten feed, and WM:corn diets are
      effective nonfeed removal methods for molting laying hens.

PMID- 15141832
TI  - Effect of food protein supplements on Salmonella enteritidis infection and
      prevention in laying hens.
AB  - Reduction of intestinal colonization of Salmonella enteritidis (SE) during the
      grow-out period is crucial to provide safer eggs, minimize economic losses, and
      reduce the spread of human salmonellosis. In the search for novel elimination and
      prevention methods based on feed supplementation, the effects of feed
      supplemented with nonimmunized egg yolk powder (did not contain anti-S.
      enteritidis antibodies), immunized egg yolk powder (with anti-S. enteritidis
      antibodies), egg yolk proteins, egg white, and skim milk powder were examined on
      laying hens. In the elimination study, the chickens were orally infected with SE
      then given a supplemented feed of 5, 10, or 15% (wt/wt) of each of the test
      samples. Fecal samples tested weekly showed an absence of SE after the first week
      of feeding nonimmunized egg yolk powder and a gradual decrease with the other
      samples. In the prevention study, Salmonella-free chickens were fed the
      supplemented feed for 4 wk and then infected orally. Fecal samples tested for 4
      wk showed that SE was prevented from colonizing the intestinal tract throughout
      the test period by nonimmunized egg yolk powder, whereas the other samples only
      delayed the colonization. None of the fed supplements disrupted the balance of
      the intestinal microflora, and the counts in the feces remained constant. These
      results show that the administration of only 5.0% (wt/wt) of nonimmunized egg
      yolk powder can eliminate and prevent SE colonization in laying hens with no
      adverse effects. Furthermore, the present results indicate that hen egg yolk
      contains novel anti-adhesive or immunomodulatory components that may act to
      prevent SE infection.

PMID- 15141833
TI  - The effects of salinomycin and roxarsone on the performance of broilers when
      included in the feed for four, five, or six weeks and infected with Eimeria
      species during the starter or grower phase of production.
AB  - The timing and magnitude of a coccidian infection, judged by the numbers of
      oocysts of Eimeria present in the litter, were affected by the duration of
      medication. In birds medicated for 6 wk and infected at 35 d of age, fewer
      oocysts were produced than in birds medicated for 4 or 5 wk whether infected at
      18 or 35 d of age. Feed conversion at 6, 7, and 8 wk of birds infected at 18 d
      and medicated for 6 wk was less than that of birds medicated for 4 or 5 wk. Birds
      infected at 35 d and medicated for 6 wk had a lower feed conversion than birds
      medicated for 5 wk. Immunity to Eimeria tenella had developed by 8 wk in birds
      medicated for 4, 5, or 6 wk if infected at 18 d of age. Immunity did not develop
      in those birds medicated for 6 wk when infected at 35 d.

PMID- 15141834
TI  - Durations of cold stress modulates overall immunity of chicken lines divergently
      selected for antibody responses.
AB  - Effects of different durations of cold stress (CS) and the time point of
      immunization relative to the CS of 3 chicken lines were studied. The first 2
      chicken lines were divergently selected for high and low antibody responses, and
      the third was a random-bred control line. In 2 experiments, 26-d-old growing
      chicks of the 3 lines were feed restricted at 80% of ad libitum and subjected to
      CS of 10 degrees C for 7, 2, or 0 d. Birds were immunized with keyhole limpet
      hemocyanin (KLH) at -1, +1, +3, +5, or +7 d relative to the end of the CS
      treatment. Specific antibodies to KLH were determined. In addition, in vitro
      lymphocyte proliferation responses to concanavalin A (ConA) and KLH as measures
      of cell-mediated immunity, production of zymosan-induced reactive oxygen
      intermediates as a measure of phagocytosis, and BW gain as a measure of a
      production trait were determined. Significantly higher antibody responses to KLH
      were found in the high line as compared with the other 2 lines. Specific antibody
      responses to KLH were not significantly affected by the CS treatments. CS had a
      delayed effect on in vitro mitogen responses to ConA. In vitro lymphocyte
      proliferation responses to ConA were higher in the low line birds than in the
      other 2 lines. In general, 7 d of CS significantly enhanced cellular immunity to
      ConA in vitro, whereas the 2-d CS treatment had differential effects on
      lymphocyte proliferation to ConA, depending on the line of bird and the time of
      immunization. KLH-specific lymphocyte proliferation was enhanced by 2 d of CS at
      28 d after immunization. Effects of various CS treatments and the time of
      immunization on the production of reactive oxygen intermediates were
      inconsistent. In addition, BW gain was negatively affected by CS. We concluded
      that the innate part of the immune system (phagocytes) responded immediately to
      CS with an as yet unexplained variability, irrespective of the genetic
      background. When CS was prolonged, the cellular adaptive immune response and, to
      some extent, the specific humoral immune response were also affected. The lack of
      line-by-treatment interactions suggested that the genetic background was a
      prominent factor for the magnitude of the specific immune response. Our data
      confirmed earlier studies that, under restricted feeding with simultaneous stress
      (energy demand for thermoregulation and growth), cellular immunity is more
      sensitive than humoral immunity. A negative correlation between BW gain and
      cellular immunity suggest a trade-off between these 2 life traits.

PMID- 15141835
TI  - Nitric oxide inhibition after Toxoplasma gondii infection of chicken macrophage
      cell lines.
AB  - Toxoplasma gondii infects many warm-blooded animals, including chickens. However,
      little is known about how this protozoan behaves within chicken macrophages.
      Thus, the microbicidal biology of HD11 and MQ-NCSU (available chicken macrophage
      cell lines) and the escaping mechanism of T. gondii were investigated. After
      infection, both cell lines were activated with lipopolysaccharide (LPS) and
      nitric oxide (NO), and reactive oxygen intermediates (ROI) were evaluated. T.
      gondii infected both cell lines, and 30 and 60% inhibition of NO production was
      detected in MQ-NCSU and HD11, respectively. In HD11, NO inhibition was not
      dependent on cyclooxygenase products. Although NO was partially inhibited, it did
      control T. gondii multiplication, showing the importance of this microbicidal
      molecule. Production of ROI was not detected in either cell line after T. gondii
      or yeast interaction. NADPH diaphorase (NADPH-d) activity, a histochemical marker
      of inducible NO synthase (iNOS), was detected at various levels in the HD11
      population activated with LPS. The HD11 population infected with T. gondii showed
      a decrease in NADPH-d, indicating that NO production inhibition was related to
      iNOS disappearance in infected macrophages. These results demonstrate that in
      chicken macrophages T. gondii can also inhibit NO production, which suggests that
      an iNOS suppression mechanism might be used for better survival in macrophages.

PMID- 15141837
TI  - Effects of Lactobacilli and an acidophilic fungus on the production performance
      and immune responses in broiler chickens.
AB  - Accumulated lines of evidence indicate that inactivated probiotics could have
      beneficial effects similar to those of live probiotics. Two strains of disrupted,
      cobalt-enriched, lactic acid bacteria (Lactobacillus acidophilus and
      Lactobacillus casei) and a disrupted fungal mycelium (Scytalidium acidophilum)
      were spray-mixed onto a mash basal feed, in 2 concentrations, prior to pelleting.
      The effects of these probiotics on production performance and immune response in
      broiler chickens were investigated. The production parameters, including BW, feed
      intake (FI), BW gain (BWG), and feed conversion ratio (FCR), were monitored
      weekly during a 6-wk trial. The immune response was evaluated by immunizing the
      birds with the antigen keyhole limpet hemocyanin (KLH) followed by a serological
      assay to measure blood IgA and IgG titers. Some of the production parameters were
      significantly improved by low L. casei (LCL; for BW and BWG), high L. acidophilus
      (LAH; for BW and BWG), and high fungal (FH; for BW, BWG, and FI) in comparison
      with the nonadditive control (NC-). However, these 3 treatments (LCL, LAH, and
      FH) did not enhance the measured immune responses. Instead, the titers of serum
      KLH-specific IgA in high L. casei (LCH) and low L. acidophilus (LAL) were
      significantly higher than those of NC-, 10 d after immunization. None of the
      probiotic treatments increased the titer of KLH-specific IgG in blood. Our
      results indicate that disrupted and cobalt-enriched L. acidophilus or L. casei
      was able to enhance production performance of broiler chickens. The fungal
      mycelium, S. acidophilum, when used at a high concentration, also demonstrated
      its potential for the first time to be used as a probiotic. In addition, the
      optimal concentration for administering probiotics is strain dependent. A higher
      dose does not always result in a better performance.

PMID- 15141836
TI  - Comparison between broilers and layers for growth and protein use by embryos.
AB  - Three experiments were conducted to compare the growth and protein utilization of
      embryo between broilers and layers. In experiments 1 and 2, the average weight of
      eggs was the same for broilers and layers. Nothing or an amino acid (AA) solution
      was injected into the eggs of broilers at d 7 of incubation, and the plasma AA
      concentration of newly hatched chicks was determined in broilers in experiment 1.
      In experiment 2, the same treatments as experiment 1 were used on layer breeder
      eggs. Plasma Tau, Thr, and Lys concentrations of hatched chicks increased when AA
      solution was injected in broilers breeder eggs (P < 0.05) but not in layers (P >
      0.05). The AA ratio to Lys was reduced by AA injection in broilers but not in
      layers. In experiment 3, weights of embryos and egg were recorded, and CP
      contents were analyzed over time during incubation (d 0, 7, 14, and 19 of
      incubation) in broilers and layers using eggs of the same weight. There were no
      differences in the weights and CP contents of embryos and eggs from broilers and
      layers. On d 14 and 19 of incubation, weights and CP contents of embryo were
      higher in broilers than layers (P < 0.05). These results suggested that the egg
      protein content might be adequate for hatching but insufficient for maximum
      growth of embryos from broilers.

PMID- 15141838
TI  - Influence of enrofloxacin administration and alpha-tocopheryl acetate
      supplemented diets on oxidative stability of broiler tissues.
AB  - The objective of this study was to assess the oxidative stability and presence of
      antibiotic residues in tissues of broilers fed diets supplemented with alpha
      tocopheryl acetate and treated with enrofloxacin. The activities of antioxidant
      enzymes and antibiotic concentrations in chicken breast, leg, and liver were
      determined. Iron-induced TBA-reactive substances (TBARS) and vitamin E were
      evaluated in muscles. The antioxidant effectiveness of vitamin E was reflected by
      TBARS values being lower in antioxidant-supplemented treatments than in the other
      dietary groups. On the other hand, antioxidant enzyme activities were not
      substantially affected by dietary treatments. The concentration of enrofloxacin
      in tissues was considerable, even after withdrawal 12 d before slaughter.
      Contrary to the findings in previous studies, enrofloxacin was not extensively
      metabolized to ciprofloxacin. Supplementation of the diet with 100 mg/kg of alpha
      tocopheryl acetate did not have a significant effect on the level of antibiotic
      found in breast muscle samples. When comparing treatments without antibiotic
      withdrawal time, alpha-tocopheryl acetate supplementation led to a significant
      decrease in enrofloxacin level in leg and liver samples. These results showed
      that mutual interactions between different molecules could modify the drug
      residues in the tissue, which should be taken into account when considering the
      drug administration and the establishment of a correct withdrawal time.

PMID- 15141839
TI  - Glucose and electrolyte supplementation of drinking water improve the immune
      responses of poults with inanition.
AB  - Enteric disorders predispose poultry to malnutrition. The objectives of this
      paper were 1) to simulate the inanition of poult enteritis mortality syndrome by
      restricting feed intake and 2) to develop a drinking water supplement that
      supports the immune functions of poults with inanition. Poults were restricted to
      14 g of feed/d for 7 d beginning at 14 d of age then fed ad libitum until 36 d
      (recovery). The control was fed ad libitum. During the feed-restriction period,
      duplicate groups of 6 poults received 1 of 5 drinking water treatments: 1)
      restricted feed, unsupplemented water; 2) restricted feed + electrolytes (RE); 3)
      RE + glucose + citric acid (REGC); 4) REGC + betaine (REGCB); or 5) REGCB + zinc
      methionine (REGCBZ). Immunological functions were assessed by inoculating poults
      with SRBC and B. abortus (BA) antigen at 15, 22, and 29 d of age. Antibody (Ab)
      titers were determined 7 d later for primary, secondary, and recovery responses.
      The primary and secondary total Ab titers to SRBC for restricted feed were 4.71
      and 6.16 log3, which where lower (P < 0.05) than for controls (8.00 and 9.66
      log3) and the other treatments. The recovery Ab titer for controls was 10.7,
      significantly higher than restricted feed (8.71) and RE (8.10) groups but not
      different from other treatments. The primary total Ab responses to BA were
      significantly lower in the restricted feed and RE groups as compared with the
      control and other treatments. Although feed restriction of poults to maintenance
      reduces the humoral immune responses, these responses can be significantly
      improved by drinking water containing electrolytes and especially sources of
      energy such as glucose and citric acid.

PMID- 15141840
TI  - Cholesterol levels and sensory characteristics of meat from broilers consuming
      moderate to high levels of alfalfa.
AB  - There is an urgent need in industrialized societies to develop novel products
      that can lower human dietary cholesterol intake. Dehydrated alfalfa is a good
      source of hypocholesterolemic compounds such as saponins. Whether consumption of
      alfalfa by chickens would decrease the cholesterol content of broiler meat
      remains, however, to be established. We determined meat quality characteristics,
      lipid and cholesterol contents, and consumer preference of broiler meat derived
      from production systems based on restricted feeding of a commercial diet combined
      with provision of free-choice dehydrated alfalfa. Results demonstrated that it
      was possible to produce chicken breast meat with reduced cholesterol content. In
      addition, total lipids in chicken meat were significantly decreased when a higher
      level of restriction was applied. Members of a 50-person consumer panel preferred
      meat from animals not consuming or consuming moderate levels of alfalfa. Those
      members that preferred meat from animals consuming the higher percentage of
      alfalfa identified taste as the primary attribute influencing that decision.
      Together the results suggest that it is possible to develop novel broiler
      production systems that will produce leaner meat that is acceptable to consumers
      and has a reduced cholesterol content.

PMID- 15141841
TI  - Development of a cannulation procedure for broiler breeder hens.
AB  - A cannulation and serial bleeding procedure has been developed to monitor the
      peripheral patterns of hormones associated with reproduction for up to 10 d in
      broiler breeder hens. Hens were cannulated via the jugular vein and returned to
      individual cages. The unrestrained cannulated hens were connected to a tether and
      swivel system that permitted constant infusion for maintenance of the cannula
      prior to serial bleeding and unrestrained long-term serial bleeding for up to 10
      d. In a short-term experiment hens were bled every 12 min for 36 h, and in a long
      term experiment hens were bled hourly for 10 d. In these experiments, 1.5-mL
      blood samples were collected at each time point with sodium citrate as the
      anticoagulant. To avoid hemodilution, after removal of plasma the red blood cells
      were reconstituted with saline to the original volume and returned to the hen of
      origin. Collection of serial blood samples was successful from 94% of hens in the
      short-term experiment and 79% of hens in the long-term experiment. Egg production
      was not affected (P > 0.05) during the 6 wk following serial bleeding in the
      short-term experiment. For hens that continued laying, egg production for 10 d
      prior to cannulation was not different (P > 0.05) from egg production for the 10
      d during serial bleeding in the long-term experiment. However, late in the
      reproductive cycle many hens (25%) stopped laying when serially bled. It is
      concluded that this cannulation procedure can be used to study short-term or long
      term peripheral patterns of hormones associated with oviposition and ovulation in
      laying broiler breeder hens.

PMID- 15141842
TI  - Preovulatory surge patterns of luteinizing hormone, progesterone, and estradiol
      17beta in broiler breeder hens fed ad libitum or restricted fed.
AB  - Spontaneous ovulations are induced by preovulatory surges of luteinizing hormone
      (LH) and progesterone (P4) during ovulatory cycles in birds, but estradiol-17beta
      (E2) levels are relatively constant. Egg production is enhanced in restricted fed
      (RF) in comparison with ad libitum fed (FF) broiler breeder hens, but changes in
      concentrations and peripheral patterns of LH, P4, and E2 during ovulatory cycles
      in broiler breeder hens are poorly documented. The hypothesis of this study was
      that high resolution patterns of peripheral LH, P4, and E2 during preovulatory
      surges would not be different between FF and RF broiler breeder hens. Seven FF
      and 6 RF broiler breeder hens were photostimulated with 16 L:8 D at 22 wk of age.
      At 28 wk of age, the hens were cannulated for serial blood sampling and switched
      to a 24L:0D photoperiod to allow preovulatory surges of LH and P4 to run freely.
      Three days after cannulation, hens were serially bled every 12 min for 36 h. The
      FF hens were heavier than the RF hens (5.60 +/- 0.35 vs. 3.60 +/- 0.28 kg,
      respectively; P < 0.01). During the 10 d before cannulation, total egg production
      of the FF and RF hens (8.3 +/- 1.4 and 6.8 +/- 1.3 eggs, respectively; P = 0.08)
      and normal egg production (5.6 +/- 1.8 and 6.5 +/- 1.8 eggs, respectively; P =
      0.37) were not different. The FF hens, however, had more abnormal eggs than the
      RF hens (2.7 +/- 1.7 and 0.3 +/- 0.8 eggs, respectively; P < 0.01). None of the
      hormonal measurements was different between the FF and RF hens (P > 0.05). The
      concentrations of hormones for the FF and RF hens, respectively, were as follows:
      baseline LH (2.79 +/- 0.45 vs. 2.94 +/- 0.60 ng/mL) and P4 (1.68 +/- 0.56 vs.
      1.41 +/- 0.43 ng/mL), overall mean LH (3.18 +/- 0.45 vs. 3.10 +/- 0.46 ng/mL) and
      P4 (2.32 +/- 0.55 vs. 2.09 +/- 0.91 ng/ mL), preovulatory surge amplitude of LH
      (5.43 +/- 1.27 vs. 3.88 +/- 1.24 ng/mL) and P4 (6.08 +/- 2.09 vs. 6.71 +/- 3.91
      ng/ mL), preovulatory surge duration of LH (7.52 +/- 1.80 vs. 5.74 +/- 3.18 h)
      and P4 (7.52 +/- 1.42 vs. 8.20 +/- 1.24 h), and overall mean E2 (0.25 +/- 0.05
      vs. 0.23 +/- 0.05 ng/mL). In conclusion, there were no differences in total egg
      production or normal egg production between FF and RF broiler breeder hens, but
      the FF hens laid more abnormal eggs. Also, there were no differences in the
      concentrations or peripheral patterns of LH, P4, and E2 during preovulatory
      surges between the FF and RF broiler breeder hens.

PMID- 15141843
TI  - Comparison of a bioassay and a liquid chromatography-fluorescence-mass
      spectrometry(n) method for the detection of incurred enrofloxacin residues in
      chicken tissues.
AB  - Regulatory monitoring for most antibiotic residues in edible poultry tissues is
      often accomplished with accurate, although expensive and technically demanding,
      chemical analytical techniques. The purpose of this study is to determine if a
      simple, inexpensive bioassay could detect fluoroquinolone (FQ) residues in
      chicken muscle above the FDA established tolerance (300 ppb) comparable to a
      liquid chromatography-fluorescencemass spectrometry(n) method. To produce
      incurred enrofloxacin (ENRO) tissues (where ENRO is incorporated into complex
      tissue matrices) for the method comparison, 40-d-old broilers (mixed sex) were
      orally dosed through drinking water for 3 d at the FDA-approved dose of ENRO (50
      ppm). At the end of each day of the 3-d dosing period and for 3 d postdosing,
      birds were sacrificed and breast and thigh muscle collected and analyzed. Both
      methods were able to detect ENRO at and below the tolerance level in the muscle,
      with limits of detection of 26 ppb (bioassay), 0.1 ppb for ENRO, and 0.5 ppb for
      the ENRO metabolite, ciprofloxacin (liquid chromatography-fluorescence-mass
      spectrometry(n)). All samples that had violative levels of antibiotic were
      detected by the bioassay. These results support the use of this bioassay as a
      screening method for examining large numbers of samples for regulatory
      monitoring. Positive samples should then be examined by a more extensive method,
      such as liquid chromatography-fluorescence-mass spectrometry(n), to provide
      confirmation of the analyte.

PMID- 15141845
TI  - The effect of a green and blue monochromatic light combination on broiler growth
      and development.
AB  - Previous reports have suggested that green light enhances broiler growth at an
      early age, whereas blue light enhances growth at older ages. The aim of this
      study was to examine the effect of a switch in monochromatic light at 2 ages on
      growth and development of broilers. Male chicks (Anak, n = 640) were used. After
      hatch, chicks were weighed, wing-banded, and blocked into treatment groups.
      Chicks were grown in 1-m2 pens in 8 isolated light-proof rooms (20 birds/pen).
      The light treatments were (1) Control white (mini-incandescent lamps), 2) blue
      light-emitting diode (LED) lamps, 3) green LED lamps, 4) blue LED switching to
      green at 10 d of age, 5) blue LED switching to green at 20 d of age, 6) green LED
      switching to blue at 10 d of age, and 7) green LED switching to blue at 20 d of
      age. There were 8 pens for treatment 1, and 4 pens for each of the other
      treatments. The light schedule was 23L:1D, and intensity was 0.1 watts/m2. BW and
      feed consumption were recorded. Green light birds were significantly heavier at 4
      d of age. Switching light at 10 d of age from green to blue caused a further
      increase in BW. This improved growth was maintained until the end of the
      experiment. Light switching from blue to green at 20 d of age also improved
      growth as compared with white light. Average feed efficiency and mortality rate
      did not differ between groups. No association was observed among light treatment,
      performance, and plasma triiodothyronine concentration. We suggest that green
      light stimulated growth of birds at early age, and shifting birds to a different
      light environment at 10 or 20 d of age might further stimulate growth.

PMID- 15141844
TI  - In vitro hypoxia differentially affects constriction and relaxation responses of
      isolated pulmonary arteries from broiler and leghorn chickens.
AB  - Under normoxic conditions in vitro, isolated pulmonary arteries from broilers
      exhibit reduced endothelium-dependent relaxation responses when compared with
      Leghorns. In vivo, hypoxia increases the susceptibility of broiler chickens to
      pulmonary hypertension syndrome (PHS), whereas Leghorns are considered resistant
      to PHS. Because L-arginine supplementation decreases the incidence of PHS in vivo
      and improves the relaxation responses of broiler isolated pulmonary arteries in
      vitro, we hypothesized that in vitro hypoxia would further reduce the relaxation
      responses of broilers to endothelium-derived nitric oxide (EDNO)-dependent
      vasodilators and that L-arginine supplementation would alleviate this impairment.
      As a test of this hypothesis, pulmonary arteries from broiler and Leghorn
      chickens were isolated and exposed to normoxia or hypoxia in the presence or
      absence of L-arginine while their constriction and relaxation responses to
      vasoactive compounds were recorded. In broilers, hypoxia did not affect the
      constriction responses of isolated pulmonary arteries but decreased EDNO
      dependent acetylcholine-induced relaxation responses. In contrast, in Leghorns
      hypoxia increased endothelin-1-induced vasoconstriction responses and reduced the
      EDNO-dependent relaxation responses only to the lowest concentration of
      acetylcholine used. L-Arginine supplementation augmented the relaxation responses
      to acetylcholine in broilers and Leghorns under normoxia but failed to augment
      them under hypoxia. Relaxation responses to the NO donor, sodium nitroprusside,
      were not affected by hypoxia in Leghorns but were increased by hypoxia in
      broilers. These results suggest that the increased incidence of PHS in broiler
      chickens reared under hypoxia may be associated with a hypoxia-induced reduction
      in the synthesis or activity of EDNO in the pulmonary circulation.

PMID- 15141846
TI  - Preventing errors in healthcare: a call for action.
AB  - Medical errors cause up to 98,000 people to die annually in the United States.
      They are the fifth leading cause of death and cost the United States dollar 29
      billion annually (Kohn 1999). Medical errors fall into 4 main categories:
      diagnostic, treatment, preventative, and other. A review of literature reveals
      several proposed solutions to the medical error problem. One solution is to
      change the system for reporting medical errors. This would allow for the tracking
      of errors and provide information on potential problematic areas. A National
      Center for Patient Safety is proposed, which would set national goals towards
      medical errors. Another solution is the setting of performance standards among
      individual entities of healthcare delivery, such as hospitals and clinics.
      Another solution involves implementing a culture of safety among healthcare
      organizations. This would put the responsibility of safety on everyone in the
      organization. A change in education is yet another proposed solution. Informing
      medical students about errors and how to deal with them will help future
      physicians prevent such errors. The final solution involves improvements in
      information technology. These improvements will help track errors, but also will
      prevent errors. A combination of these solutions will change the focus of the
      healthcare industry toward safety and will eventually lead to billions in
      savings, but more importantly, the saving of lives.

PMID- 15141848
TI  - The role of value in provider-patient-payer relationships.
AB  - Value is becoming a topic of interest to 3 key players in the healthcare field
      patients, payers, and providers. This article examines various value definitions
      and puts forth a composite value definition incorporating cost, quality, and
      worth elements. A value triad is created to demonstrate how value can be a
      linking mechanism between patient, payers and providers. Examples are then
      provided to assist managers in examining the value associated with payers and
      patients.

PMID- 15141847
TI  - Diversity management: an imperative for healthcare organizations.
AB  - Historically, white males have represented the ideal manager in appearance,
      values, and behaviors, resulting in overt or subtle discrimination in selection,
      evaluation, and promotion practices in corporate America. Because women and
      minorities could not meet this ideal, they were often passed over for
      advancement. The author discusses key areas of diversity management for
      healthcare administrators to consider: the elements of diversity, the reasons
      behind diversity management, and solutions for addressing many of the issues
      involved.

PMID- 15141849
TI  - Privacy--private lives, public lives.

PMID- 15141850
TI  - Why do nurses leave and what can health oganizations do to retain them?

PMID- 15141851
TI  - A big push.

PMID- 15141852
TI  - Introduction: consequences of terrorism.
AB  - Recent acts of terrorism have ranged from the dissemination of anthrax spores to
      intentional contamination of food to the release of chemical weapons to suicide
      attacks using explosives. The prediction of such events is difficult, if not
      impossible. The recent attacks that have generated massive numbers of injured and
      dead may signal the crossing of a new threshold from multi-casualty events to the
      use of weapons of mass destruction. Consequently, the medical and healthcare
      infrastructure must be able to prevent and treat illness and injury resulting
      from such events. Thus, a first step in improving the preparation for and
      responses to such events must include a sustained commitment to training
      physicians, nurses, identification specialists, pathologists, and other first
      responders. The rapid spread of SARS gives reason to believe that the
      distribution of such agents has potential advantages over the use of other
      weapons. Investments in the public health and healthcare systems provide the best
      defense against terrorism.

PMID- 15141853
TI  - Terrorism, disasters, and security.
AB  - The purpose of this editorial is to explore the relationship between the new
      global emphasis on terrorism and the developing academic and practical fields of
      disaster management. It includes an appraisal of the place of terrorism among the
      various forms of disaster, a consideration of its relationship to risk assessment
      and its place in the practical handling of risks and incidents, and some
      reflections on the role of the private sector in security management. The
      influence on the current attitude toward managing the terrorism threat by the
      evolution of the disaster management field is considered and some of the problems
      with defining scenarios for counter-terrorism planning also are discussed.

PMID- 15141854
TI  - Ethical considerations in emergency planning, preparedness, and response to acts
      of terrorism.
AB  - Throughout the globe, healthcare providers are increasingly challenged with the
      specter of terrorism and the fallout from weapons of mass destruction. Preparing
      for and responding to such manmade emergencies, however, threatens the ethical
      underpinnings of routine, individualized, patient-centered, emergency healthcare.
      The exigency of a critical incident can instantly transform resource rich
      environs, to those of austerity. Healthcare workers, who only moments earlier may
      have been seeing two to three patients per hour, are instantly thrust into a sea
      of casualties and more basic lifeboat issues of quarantine, system overload and
      the thornier determinations of who will be given every chance to live and who
      will be allowed to die. Beyond the tribulations of triage, surge capacity, and
      the allocation of scarce resources, terrorism creates a parallel need for a host
      of virtues not commonly required in daily medical practice, including prudence,
      courage, justice, stewardship, vigilance, resilience, and charity. As a
      polyvalent counterpoint to the vices of apathy, cowardice, profligacy,
      recklessness, inflexibility, and narcissism, the virtues empower providers at all
      levels to vertically integrate principles of safety, public health, utility, and
      medical ethics at the micro, meso, and macro levels. Over time, virtuous behavior
      can be modeled, mentored, practiced, and institutionalized to become one of our
      more useful vaccines against the threat of terrorism in the new millennium.

PMID- 15141855
TI  - Aum Shinrikyo and the Japanese law on bioterrorism.
AB  - Before the sarin incidents in Tokyo and Matsumoto, the Aum Shinrikyo (now Aleph)
      had tried to conduct bioterrorism with botulinum toxin and Bacillus anthracis.
      Followers of the Aum could not overcome technical difficulties inherent in
      developing biological weapons, and the perpetrators had not been prosecuted for
      their failed attempts of bioterrorism. But the Aum's biological attack revealed
      several shortcomings in the Japanese law that regulated biological weapons. Since
      the missile experiment of North Korea conducted in 1998, the Japanese government
      has come to consider the threat posed by biological weapons more seriously. In
      2001, after the 11 September 2001 terrorist attacks and the series of anthrax
      letter scares in the United States of America, the Japanese government
      established its Five Basic Principles for Chemical and Biological Weapons
      Terrorism and several measures were taken at the central and local levels.
      Activities of the Aum have been monitored by the Public Security Investigation
      Agency and the National Police Agency under the Anti-Aum Law since 2000.

PMID- 15141856
TI  - Educational and training systems in Sweden for prehospital response to acts of
      terrorism.
AB  - Sweden has a long tradition in planning for disaster situations in which the
      National Board of Health and Welfare has a key responsibilty within the health
      sector. One important part of this disaster preparedness is education and
      training. Since 11 September 2001, much focus has been placed on the acts of
      terrorism with special reference to the effects of the use of chemical,
      biological, or nuclear/radiological (CBNR) agents. In the health sector, the
      preparedness for such situations is much the same as for other castastrophic
      events. The National Board of Health and Welfare of Sweden is a national
      authority under the government, and one of its responsibilities is planning and
      the provision of supplies for health and medical services, environmental health,
      and social services in case of war or crises. "Joint Central Disaster Committees"
      in each County Council/Region in the country are responsible for overseeing major
      incident planning for their respective counties/regions. The "Disaster Committee"
      is responsible for ensuring that: (1) plans are established and revised; (2) all
      personnel involved in planning receive adequate information and training; (3)
      equipment and supplies are available; and (4) maintenance arrangements are in
      place. Sweden adopts a "Total Defense" strategy, which means that it places a
      high value in preparing for peacetime and wartime major incidents. The Swedish
      Emergency Management Agency coordinates the civilian Total Defense strategy, and
      provides funding to the relevant responsible authority to this end. The National
      Board of Health and Welfare takes responsibility in this process. In this area,
      the main activities of the National Board of Health and Welfare are: (1) the
      establishment of national guidelines and supervision of standards in emergency
      and disaster medicine, social welfare, public health, and prevention of
      infectious diseases; (2) the introduction of new principles, standards, and
      equipment; (3) the conducting education and training programmes; and (4) the
      provision of financial support. The budget for National Board of Health and
      Welfare in this area is approximately 160 million SEK (US dollar 18 million). The
      National Board of Health and Welfare also provides funding to the County
      Councils/Regions for the training of healthcare professionals in disaster
      medicine and crises management by arranging (and financing) courses primarily for
      teachers and by providing financial support to the County Councils/Regions for
      providing their own educational and training programmes. The National Board of
      Health and Welfare provides funding of approximately 20 million SEK (US dollar
      2.4 million) to the County Councils/Regions for this training of healthcare
      professionals in disaster medicine and crises.

PMID- 15141857
TI  - The chemical disaster response system in Japan.
AB  - During the last decade, Japan has experienced the largest burden of chemical
      terrorism-related events in the world, including the: (1) 1994 Matsumoto sarin
      attack; (2) 1995 Tokyo subway sarin attack; (3) 1998 Wakayama arsenic incident;
      (4) 1998 Niigata sodium-azide incident; and (5) 1998 Nagano cyanide incident. Two
      other intentional cyanide releases in Tokyo subway and railway station restrooms
      were thwarted in 1995. These events spurred Japan to improve the following
      components of its chemical disaster-response system: (1) scene demarcation; (2)
      emergency medical care; (3) mass decontamination; (4) personal protective
      equipment; (5) chemical detection; (6) information-sharing and coordination; and
      (7) education and training. Further advances occurred as result of potential
      chemical terrorist threats to the 2000 Kyushu-Okinawa G8 Summit, which Japan
      hosted. Today, Japan has an integrated system of chemical disaster response that
      involves local fire and police services, local emergency medical services (EMS),
      local hospitals, Japanese Self-Defense Forces, and the Japanese Poison
      Information Center.

PMID- 15141858
TI  - Lack of hospital preparedness for chemical terrorism in a major US city: 1996
      2000.
AB  - INTRODUCTION: The [US] Nunn-Lugar-Domenici Defense Against Weapons of Mass
      Destruction (WMD) Act (the WMD Act of 1996) heralded a new wave of spending by
      the federal government on counter-terrorism efforts. Between 1996 and 2000, the
      United States of America (US) federal government allocated large sums of funding
      to the States for bioterrorism preparedness. Distribution of these funds between
      institutions involved in first-responder care (e.g., fire and safety departments)
      and hospitals was uneven. It is unknown whether these additional funds had an
      impact on the level of hospital preparedness for managing mass casualties
      involving hazardous materials at the local level, including potential terrorist
      attacks with chemical agents. OBJECTIVES: (1) To compare 1996 and 2000 measures
      of preparedness among hospitals of a major US metropolitan area for dealing with
      hazardous material casualties, including terrorism that involved the use of
      weapons of mass destruction; and (2) To provide guidance for the improvement of
      emergency preparedness and response in US hospitals. METHODS: In July 1996 and
      again in July 2000,21 hospitals in one major US city were surveyed by
      questionnaire. A survey was used to assess the amounts of antidote stocks held
      available for treatment of casualties caused by toxic chemical agents and
      institutional response capabilities including the number of showers for
      decontaminating patients, the level of worker protection, and the number of staff
      trained to decontaminate patients. RESULTS: Hospital preparedness for treating
      and decontaminating patients exposed to toxic chemical agents was inadequate in
      1996 and in 2000. From 1996 to 2000, there was no statistically significant
      change in the lack of hospital preparedness for stocking of nerve agent and
      cyanide antidotes. Capacity for decontamination of patients, which included
      appropriate hazardous material infrastructure and trained staff, generally was
      unimproved from 1996 to 2000 with the exception of an increase of nearly 30% in
      hospitals with at least one decontamination shower facility. CONCLUSION:
      Hospitals surveyed in this study were poorly prepared to manage chemical
      emergency incidents, including terrorism. This lack of hospital preparedness did
      not change significantly between 1996 and 2000 despite increased funds allocated
      to bioterrorism preparedness at the local level.

PMID- 15141859
TI  - Decontamination of mass casualties--re-evaluating existing dogma.
AB  - The events of 11 September 2001 became the catalyst for many to shift their
      disaster preparedness efforts towards mass-casualty incidents. Emergency
      responders, healthcare workers, emergency managers, and public health officials
      worldwide are being tasked to improve their readiness by acquiring equipment,
      providing training and implementing policy, especially in the area of mass
      casualty decontamination. Accomplishing each of these tasks requires good
      information, which is lacking. Management of the incident scene and the approach
      to victim care varies throughout the world and is based more on dogma than
      scientific data. In order to plan effectively for and to manage a chemical, mass
      casualty event, we must critically assess the criteria upon which we base our
      response. This paper reviews current standards surrounding the response to a
      release of hazardous materials that results in massive numbers of exposed human
      survivors. In addition, a significant effort is made to prepare an international
      perspective on this response. Preparations for the 24-hour threat of exposure of
      a community to hazardous material are a community responsibility for first
      responders and the hospital. Preparations for a mass-casualty event related to a
      terrorist attack are a governmental responsibility. Reshaping response protocols
      and decontamination needs on the differences between vapor and liquid chemical
      threats can enable local responders to effectively manage a chemical attack
      resulting in mass casualties. Ensuring that hospitals have adequate resources and
      training to mount an effective decontamination response in a rapid manner is
      essential.

PMID- 15141860
TI  - Future considerations for the medical management of nerve-agent intoxication.
AB  - The use of chemical warfare agents against civilians and unprotected troops in
      international conflicts or by terrorists against civilians is considered to be a
      real threat, particularly following the terrorist attacks on 11 September 2001
      against the World Trade Center in New York and against the Pentagon in
      Washington, DC. Over the past 10 years, terrorists have been planning to use or
      have used chemical warfare agents on several occasions around the world, and the
      attacks in 2001 illustrate their willingness to use any means of warfare to cause
      death and destruction among civilians. In spite of new international treaties
      with strong verification measures and with an aim to prohibit and prevent the use
      of weapons of mass destruction, nevertheless, some countries and terrorist groups
      have been able to develop, produce, and use such weapons, particularly nerve
      agents, in domestic terrorist attacks or during warfare in international
      conflicts. This article reviews current medical therapy for nerve-agent
      intoxication and discusses possible future improvement of medical therapies.
      Present medical counter-measures against nerve agents are not sufficiently
      effective particularly in protecting the brain. Therefore, new and more effective
      countermeasures must be developed to enable better medical treatment of civilians
      and military personnel following exposure to nerve agents. Therefore, it is
      important with an enhanced effort by all countries, to improve and increase
      research in medical countermeasures, in the development of protective equipment,
      and in carrying out regular training of medical and emergency personnel as well
      as of military nuclear, biological, or chemical (NBC) units. Only then will
      nations be able to reduce the risk from and prevent the use of such weapons of
      mass destruction (WMD).

PMID- 15141861
TI  - Public health response actions and the use of emergency operations centers.
AB  - In the wake of 11 September 2001, many public health agencies are reassessing
      their institutional capabilities and procedures to respond to mass-casualty
      incidents involving weapons of mass destruction. Prior to the fall of 2001,
      planning by the public health and other sectors addressed more conventional or
      naturally occurring events such as earthquakes, hurricanes, tornados, and
      chemical spills, although attacks with weapons of mass destruction were a growing
      concern. While the nature of natural versus intentional events differs, the
      management and coordination of response activities to them follows the same
      incident command system. A major lesson learned during the response operations to
      the 11 September 2001 attacks in New York City was the value of disaster
      planning, conducting exercises, and developing relationships among the various
      response agencies. Although New York City's physical Emergency Operations Center
      (EOC) at 7 World Trade Center was destroyed in the attack, the medical and health
      response community was able to react effectively to the possibility of mass
      casualties as well as to the more usual needs. This was enabled by the pre
      existing relationships that had been developed between city, state, federal, and
      non-governmental agencies while planning and exercising for such events and their
      aftermaths.

PMID- 15141862
TI  - Mass-casualty, terrorist bombings: epidemiological outcomes, resource
      utilization, and time course of emergency needs (Part I).
AB  - INTRODUCTION: This article characterizes the epidemiological outcomes, resource
      utilization, and time course of emergency needs in mass-casualty, terrorist
      bombings producing 30 or more casualties. METHODS: Eligible bombings were
      identified using a MEDLINE search of articles published between 1996 and October
      2002 and a manual search of published references. Mortality, injury frequency,
      injury severity, emergency department (ED) utilization, hospital admission, and
      time interval data were abstracted and relevant rates were determined for each
      bombing. Median values for the rates and the inter-quartile ranges (IQR) were
      determined for bombing subgroups associated with: (1) vehicle delivery; (2)
      terrorist suicide; (3) confined-space setting; (4) open-air setting; (5)
      structural collapse sequela; and (6) structural fire sequela. RESULTS: Inclusion
      criteria were met by 44 mass-casualty, terrorist bombings reported in 61
      articles. Median values for the immediate mortality rates and IQRs were: vehicle
      delivery, 4% (1-25%); terrorist-suicide, 19% (7-44%); confined-space 4% (1-11%);
      open-air, 1% (0-5%); structural-collapse, 18% (5-26%); structural fire 17% (1
      17%); and overall, 3% (1-14%). A biphasic pattern of mortality and unique
      patterns of injury frequency were noted in all subgroups. Median values for the
      hospital admission rates and IQRs were: vehicle-delivery, 19% (14-50%); terrorist
      suicide, 58% (38-77%); confined-space, 52% (36-71%); open-air, 13% (11-27%);
      structural-collapse, 41% (23-74%); structural-fire, 34% (25-44%); and overall,
      34% (14-53%). The shortest reported time interval from detonation to the arrival
      of the first patient at an ED was five minutes. The shortest reported time
      interval from detonation to the arrival of the last patient at an ED was 15
      minutes. The longest reported time interval from detonation to extrication of a
      live victim from a structural collapse was 36 hours. CONCLUSION: Epidemiological
      outcomes and resource utilization in mass-casualty, terrorist bombings vary with
      the characteristics of the event.

PMID- 15141863
TI  - Mass-casualty, terrorist bombings: implications for emergency department and
      hospital emergency response (Part II).
AB  - This article reviews the implications of mass-casualty, terrorist bombings for
      emergency department (ED) and hospital emergency responses. Several practical
      issues are considered, including the performance of a preliminary needs
      assessment, the mobilization of human and material resources, the use of personal
      protective equipment, the organization and performance of triage, the management
      of explosion-specific injuries, the organization of patient flow through the ED,
      and the efficient determination of patient disposition. As long as terrorists use
      explosions to achieve their goals, mass-casualty, terrorist bombings remain a
      required focus for hospital emergency planning and preparedness.

PMID- 15141864
TI  - The impact of terrorism on children: a two-year experience.
AB  - OBJECTIVES: To review and analyze the cumulative two-year, Israeli experience
      with medical care for children victims of terrorism during the prehospital and
      hospital phases. METHODS: Data were collected from the: (1) Magen David Adom
      National Emergency Medical System Registry (prehospital phase); (2) medical
      records from the authors' institutions (pediatric triage); and (3) Israel Trauma
      Registry (injury characteristics and utilization of in-hospital resources).
      Statistical analyses were performed as appropriate. INTRODUCTION: During the
      recent wave of violence in Israel and the surrounding region, hundreds of
      children have been exposed to and injured by terrorist attacks. There is a
      paucity of data on the epidemiology and management of terror-related trauma in
      the pediatric population and its effects on the healthcare system. This study
      focuses on four aspects of terrorism-related injuries: (1) tending to victims in
      the prehospital phase; (2) triage, with a description of a modified, pediatric
      triage algorithm; (3) characteristics of trauma-related injuries in children; and
      (4) utilization of in-hospital resources. RESULTS: During the study period, 41
      mass-casualty events (MCEs) were managed by Magen David Adom. Each event involved
      on average, 32 regular and nine mobile intensive care unit ambulances with 93
      medics, 19 paramedics, and four physicians. Evacuation time was 5-10 minutes in
      urban areas and 15-20 minutes in rural areas. In most cases, victims were
      evacuated to multiple facilities. To improve efficiency and speed, the Magen
      David Adom introduced the use of well-trained "first-responders" and volunteer,
      off-duty professionals, in addition to "scoop and run" on-the-scene management.
      Because of differences in physiology and response between children and adults, a
      pediatric triage algorithm was developed using four categories instead of the
      usual three. Analysis of the injuries sustained by the 160 children hospitalized
      after these events indicates that most were caused by blasts and penetration by
      foreign objects. Sixty-five percent of the children had multiple injuries, and
      the proportion of critical to fatal injuries was high (18%). Compared to children
      with non-terrorism-related injuries, the terrorism-related group had a higher
      rate of surgical interventions, longer hospital stays, and greater needs for
      rehabilitation services. CONCLUSION: Terrorism-related injuries in children are
      severe and increase the demand for acute care. The modifications in the
      management of pediatric casualties from terrorism in Israel may contribute to the
      level of preparedness of medical and paramedical personnel to cope with future
      events. Further studies of other aspects of traumatic injuries, such as its short
      and long-term psychological consequences, will provide a more comprehensive
      picture of the damage inflicted on children by acts of terrorism.

PMID- 15141865
TI  - Case report: penetrating cardiac injury secondary to a terrorism-related nail
      bomb explosion.
AB  - Penetrating cardiac injuries commonly occur secondary to gunshot or stab wounds.
      This is a report an unusual case of a patient who sustained a penetrating cardiac
      injury due to a nail from a terrorism-related, nail-bomb explosion. Associated
      problems included pericardial tamponade, penetrating cardiac injuries, acute,
      traumatic, myocardial infarction, and a penetrating lung injury. Prompt diagnosis
      and aggressive surgical intervention resulted in full recovery of the patient.

PMID- 15141866
TI  - The spectrum of human reactions to terrorist attacks with weapons of mass
      destruction: early management considerations.
AB  - Residents of a community who are intentionally exposed to a hazardous biological,
      chemical, or radiological agent (including medical first-responders and other
      civil defense personnel who live in that community) will exhibit a spectrum of
      psychological reactions that will impact the management of the incident. These
      reactions will range from a variety of behaviors of normal people under abnormal
      circumstances that either will help or hinder efforts to contain the threatening
      agent, deliver medical care, and reduce the morbidity, mortality, and costs
      associated with the disaster, to the development of new, or exacerbation of
      preexisting, mental disorders. Anticipating the decisions that people will make
      and actions they will take as the crisis develops is hindered by the limited
      number of previous disasters that bear crucial similarities to a terrorist attack
      with a weapon of mass destruction. Such actions, therefore, could serve as models
      to predict community reactions. One result of a study that attempted to fill in
      these gaps suggested that medical first-responders and their spouses/significant
      others may require separately crafted information and advice to reduce the
      potential for disharmony within the family that could affect job performance
      during the crisis. For those persons who exhibit emotional lability or cognitive
      deficits, evaluation of their psychiatric signs and symptoms may be more
      difficult than imagined, especially with exposure to nerve agents. Appreciation
      of these difficulties, and possession of the skill to sort through them, will be
      required of those assigned to triage stations. The allocation and utilization of
      mental health resources as the incident unfolds will be the responsibility of
      local consequence managers; these managers should be aware of the results of a
      recently-held workshop that attempted to reach consensus among experts in
      disaster mental health, based on the peer-reviewed literature, on the efficacy
      and safety of various approaches to early psychological interventions for victims
      of mass trauma and disasters. Thus, psychological factors are likely to be
      significant in the management of a terrorist incident that involves an agent of
      mass destruction. Emergency medical workers with managerial responsibilities,
      whether limited in scope or community-wide, should be aware of these factors, and
      should train to handle them through effective risk communication as part of their
      planning and preparation.

PMID- 15141867
TI  - Measures of effectiveness in large-scale bioterrorism events.
AB  - Measures of effectiveness (MOEs) are defined as operationally quantifiable
      management tools that provide a means for measuring effectiveness, outcome, and
      performance. No clear MOEs exist for determining success or failure of the
      management of a bioterrorism response. This is especially critical because
      management requires a multi-agency and multi-disciplinary decision-making and
      evaluation process. It is suggested that the minimum MOEs required to
      operationally measure outcome must contain a measuring response capacity for: (1)
      real-time public health surveillance system; (2) full coverage health information
      system; (3) capacity to measure variance across management timelines; (4)
      demonstrated decline in mortality and morbidity; (5) control of transmission
      rates of communicable agents; and (6) resource distribution across the entire
      population.

PMID- 15141868
TI  - From complex emergencies to terrorism--new tools for health-sector coordination
      in conflict-associated disasters.
AB  - Inter-agency coordination in humanitarian assistance dates as a discipline from
      the 1960s. The United Nations, Red Cross, governmental, and non-governmental
      agencies have evolved different mechanisms to achieve it. Present practices in
      field-based, inter-agency coordination of the health sector remain variable and
      non-standardized. International experiences in coordination of humanitarian
      assistance reveal numerous issues of jurisdiction, authority, capacity, and
      competency. New tools to help overcome these issues in the health-sector
      coordination include binding principles of engagement, protocols for the
      assumption of responsibilities, standardized minimum essential data sets, and
      health-sector component summaries.

PMID- 15141869
TI  - Health implications of cyber-terrorism.
AB  - The world is becoming ever more interconnected via the Internet, creating both
      benefits and disadvantages for human communities. This article examines cyber
      terrorism, one of the major negative consequences of the Internet. It also
      examines the potential impact of cyber-terrorism on the health of populations,
      its possible perpetrators, and its prevention and control.

PMID- 15141870
TI  - Comparison of methods for differentiation of Salmonella enterica serovar
      Enteritidis phage type 4 isolates.
AB  - OBJECTIVE: To compare molecular typing methods for the differentiation of
      Salmonella enterica serovar Enteritidis phage type (PT) 4 isolates that allowed
      for the determination of their genetic relatedness. SAMPLE POPULATION: 27
      Salmonella Enteritidis PT 4 strains isolated in the United States and Europe.
      PROCEDURE: Several molecular typing methods were performed to assess their
      ability to genetically differentiate among Salmonella Enteritidis PT 4 isolates.
      Results of pulse-field gel electrophoresis (PFGE), repetitive polymerase chain
      reaction (PCR) assay, 16S rRNA gene sequencing, random amplification of
      polymorphic DNA (RAPD), PCR-restriction fragment length polymorphism of 16S rRNA,
      and antimicrobial susceptibility were evaluated. RESULTS: Compared with results
      for other techniques, results for the RAPD typing method with the RAPD1 primer
      reveal that it was the most discriminatory fingerprinting technique, and it
      allowed us to cluster Salmonella Enteritidis PT 4 isolates on the basis of their
      genetic similarity. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed the
      value of RAPD with the RAPD1 primer as a tool for epidemiologic investigations of
      Salmonella Enteritidis PT 4. It can be used in conjunction with PFGE and phage
      typing to determine the genetic relatedness of Salmonella Enteritidis isolates
      involved in outbreaks of disease. A reliable and highly discriminatory method for
      epidemiologic investigations is critical to allow investigators to identify the
      source of infections and consequently prevent the spread of Salmonella
      Enteritidis PT 4.

PMID- 15141871
TI  - Three-dimensional motion pattern of the caudal lumbar and lumbosacral portions of
      the vertebral column of dogs.
AB  - OBJECTIVE: To evaluate the 3-dimensional motion pattern including main and
      coupled motions of the caudal lumbar and lumbosacral portions of the vertebral
      column of dogs. ANIMALS: Vertebral columns of 9 German Shepherd Dogs (GSDs) and
      16 dogs of other breeds with similar body weights and body conditions. PROCEDURE:
      Main and coupled motions of the caudal lumbar and lumbosacral portions of the
      vertebral column (L4 to S1) were determined by use of a testing apparatus that
      permitted precise application of known pure moments to the vertebral column.
      Motion was compared between GSDs and dogs of other breeds. RESULTS: All specimens
      had a similar motion pattern consisting of main motion and a certain amount of
      coupled motion including translation. Vertebral columns of GSDs had significantly
      less main motion in all directions than that of dogs of other breeds. Translation
      was similar in GSDs and dogs of other breeds and was smallest at the lumbosacral
      motion segment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that motion
      in the caudal lumbar and lumbosacral portions of the vertebral column of dogs is
      complex and provided a basis for further studies evaluating abnormal vertebral
      columns.

PMID- 15141872
TI  - Histomorphologic and morphometric evaluation of the uterine horns in nulliparous
      and multiparous Beagles.
AB  - OBJECTIVE: To macroscopically, histomorphologically, and morphometrically compare
      uterine tissues obtained from nulliparous and multiparous dogs. ANIMALS: 12 dogs
      constituting 2 homogenous groups (7 nulliparous Beagles and 5 multiparous
      Beagles, each of which had at least 7 pregnancies). PROCEDURE: Serum
      concentrations of progesterone and estradiol-17beta were determined. Samples of
      uterine tissues were fixed, embedded in paraffin, and cut into serial cross
      sections. Morphometric analysis was performed on systematically selected
      trichrome-stained sections. RESULTS: Mean absolute volume of the uterine wall did
      not differ between groups. Volume of blood vessels was significantly higher and
      relative mean value for myometrial connective tissue was significantly lower in
      the multiparous dogs. Arteries in the myometrium of multiparous dogs had
      pronounced thickening of the intima (ie, pregnancy sclerosis) and a concomitant
      thinning of the smooth muscle layer (tunica media). Furthermore, the elastica
      interna of these arteries appeared to be disintegrating and was highly and
      irregularly folded. Adventitia of the myometrial veins in multiparous dogs
      contained numerous layers of elastic fibers; however, only a few layers were
      observed in the adventitia of corresponding veins in nulliparous dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE: In this study, we documented that in contrast
      to other species, the uterus of nonpregnant dogs does not increase in size and
      volume even after at least 7 pregnancies. Furthermore, sclerotic alterations of
      uterine arteries are proof of at least 1 pregnancy. Results of this study may be
      useful in the evaluation of uterine diseases.

PMID- 15141873
TI  - Evaluation of protective immunity in pigs following oral administration of an
      avirulent live vaccine of Lawsonia intracellularis.
AB  - OBJECTIVE: To evaluate the efficacy of an orally administered avirulent live
      vaccine to protect pigs against challenge exposure with virulent Lawsonia
      intracellularis. ANIMALS: 108 weaned 3-week-old pigs (35 in experiment 1 and 73
      in experiment 2). PROCEDURE: 2 experiments were conducted. On day 0, vaccinates
      were orally administered vaccine via drench or in drinking water, whereas
      challenge-control pigs were administered cultured medium. On day 21, pigs were
      challenge exposed with a virulent heterologous isolate of L. intracellularis.
      Clinical observations, weights, seroconversion, and fecal excretion of L.
      intracellularis were measured until day 42. At study termination, pigs were
      euthanatized and examined for L. intracellularis-specific lesion development of
      the ileum and colon. RESULTS: Pigs receiving a single dose of vaccine were
      protected when challenge exposed with virulent L. intracellularis (at least
      10(77) TCID50/dose). In experiment 1, vaccinates had significantly less fecal
      excretion (47% and 40% for days 35 and 42, respectively), compared with challenge
      control pigs. In experiment 2, vaccinates had significantly less fecal excretion
      (50% and 58% for days 35 and 42, respectively), compared with challenge-control
      pigs. Significant reductions in lesion development were evident in the ileum of
      vaccinated pigs (70% and 56% at day 42 for experiments 1 and 2, respectively),
      compared with challenge-control pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Oral
      administration by drench or via drinking water of an avirulent live vaccine
      against L. intracellularis resulted in substantial protection against
      proliferative enteropathy among vaccinates and offers a better way to reduce
      stress of pigs during vaccine administration.

PMID- 15141874
TI  - Quantification, repeatability, and reproducibility of feline radial and
      longitudinal left ventricular velocities by tissue Doppler imaging.
AB  - OBJECTIVE: To measure the radial and longitudinal velocities of several
      myocardial segments of the left ventricular wall by use of tissue Doppler imaging
      (TDI) in healthy cats and determine the repeatability and reproducibility of the
      technique. ANIMALS: 6 healthy cats. PROCEDURE: 72 TDI examinations were performed
      on 4 days by the same trained observer. Radial parameters included left
      endocardial and epicardial myocardial velocities. Longitudinal parameters
      included left basal, middle, and apical myocardial velocities. RESULTS: All
      velocity profiles had 1 positive systolic wave (S) and 2 negative diastolic waves
      (E and A). Myocardial velocities were higher in the endocardial than epicardial
      segments during the entire cardiac cycle (systolic wave S, 4.4 +/- 0.82 and 1.9
      +/- 0.55; diastolic wave E, 9.7 +/- 1.70 and 2.2 +/- 0.74; and diastolic wave A,
      5.1 +/- 1.56 and 1.4 +/- 0.76, respectively). Velocities were also higher in the
      basal than in the apical segments (systolic wave S, 4.7 +/- 0.76 and 0.2 +/-
      0.11; diastolic wave E, 9.7 +/- 1.36 and 0.5 +/- 0.17; and diastolic wave A, 3.7
      +/- 1.51 and 0.2 +/- 0.13, respectively). The lowest within-day and between-day
      coefficients of variation were observed in endocardial segments (8.2% and 6.5%
      for systolic wave S and diastolic wave E, respectively) and in the basal segment
      in protodiastole (5.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Repeatability and
      reproducibility of TDI were adequate for measurement of longitudinal and radial
      left ventricular motion in healthy awake cats. Validation of TDI is a
      prerequisite before this new technique can be recommended for clinical use.

PMID- 15141875
TI  - Comparison of surgical techniques for synovectomy in New Zealand White rabbits
      with induced inflammatory arthritis.
AB  - OBJECTIVE: To compare effects of synovectomy performed by use of monopolar
      radiofrequency energy (MRFE) versus mechanical debridement in rabbits with
      induced inflammatory arthritis. ANIMALS: 25 mature female New Zealand White
      rabbits. PROCEDURE: Inflammatory arthritis was induced in both femoropatellar
      joints of each rabbit. Joints then were treated by mechanical debridement or MRFE
      treatment or served as sham-operated controls. Rabbits were euthanatized 2 weeks
      or 3 months after surgery. Biopsy specimens of synovium were analyzed by use of
      light microscopy. RESULTS: At 2 weeks after surgery, samples from MRFE-treated
      joints had fewer plasma cells and more heterophils than the other 2 groups and
      more lymphocytes than sham-operated controls, whereas samples from mechanically
      debrided joints had greater numbers of lymphocytes and heterophils than sham
      operated controls. At 3 months after surgery, samples from MRFE-treated joints
      had fewer plasma cells than sham-operated controls, more heterophils than
      mechanically debrided and sham-operated controls, and more macrophages than
      mechanically debrided joints. There was no difference in synovial ablation,
      synovial proliferation, or fibrosis among the 3 groups at 2 weeks or 3 months
      after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this
      study documented a similar degree of synovial ablation when comparing use of MRFE
      to mechanical debridement. In rabbits with this method of induced inflammatory
      arthritis, there were no detectable benefits of MRFE or mechanical debridement on
      the synovium, compared with results for sham-operated control joints, at 2 weeks
      and 3 months after surgery for most of the synovial variables evaluated.

PMID- 15141876
TI  - Assessment of apoptosis in epidermal lamellar cells in clinically normal horses
      and those with laminitis.
AB  - OBJECTIVE: To determine and compare the number, type, location, and distribution
      of apoptotic epidermal cells in the laminae of clinically normal horses and
      horses with laminitis. SAMPLE POPULATION: Formalin-fixed samples of digital
      lamellar tissue from 47 horses (including clinically normal horses [controls; n =
      7], horses with acute [4] and chronic [7] naturally acquired laminitis, and
      horses with black walnut extract-induced [11] or carbohydrate overload-induced
      [18] laminitis). PROCEDURE: Blocks of paraffin-embedded lamellar tissues were
      stained for DNA fragmentation with the terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL) technique. Differential
      immunohistochemical staining for caspases 3 and 14 were used to confirm
      apoptosis. RESULTS: The number of TUNEL-positive epidermal cells per 0.1 mm of
      primary laminae was significantly greater in the acute laminitis group than in
      the other groups. In the acute laminitis group, there were 17 and 1,025 times as
      many TUNEL-positive basal layer cells and keratinocytes, respectively, compared
      with the control group. Apoptosis of TUNEL-positive basal layer cells was
      confirmed by results of caspase 3 immunohistochemical staining. The TUNEL
      positive keratinocytes did not stain for caspases 3 or 14. CONCLUSIONS AND
      CLINICAL RELEVANCE: The large number of apoptotic basal layer cells detected in
      the lamellar tissue of horses with acute naturally acquired laminitis suggests
      that apoptosis may be important in the development of acute laminitis. The role
      of the large number of TUNEL-positive keratinocytes detected in the interface of
      primary and secondary epidermal laminae of horses with acute laminitis remains to
      be elucidated.

PMID- 15141877
TI  - Effect of dietary soy on serum thyroid hormone concentrations in healthy adult
      cats.
AB  - OBJECTIVE: To compare effects of short-term administration of a soy diet with
      those of a soy-free diet on serum thyroid hormone concentrations in healthy adult
      cats. ANIMALS: 18 healthy adult cats. PROCEDURE: Cats were randomly assigned to
      receive either a soy or soy-free diet for 3 months each in a crossover design.
      Assays included CBC, serum biochemical profile, thyroid hormone analysis, and
      measurement of urinary isoflavone concentrations. RESULTS: Genistein, a major soy
      isoflavone, was identified in the urine of 10 of 18 cats prior to dietary
      intervention. Compared with the soy-free diet, cats that received the soy diet
      had significantly higher total thyroxine (T4) and free T4 (fT4) concentrations,
      but unchanged total triiodothyronine (T3) concentrations. The T3/fT4 ratio was
      also significantly lower in cats that received the soy diet. Although the
      magnitudes of the increases were small (8% for T4 and 14% for fT4), these changes
      resulted in an increased proportion of cats (from 1/18 to 4/18) that had fT4
      values greater than the upper limit of the laboratory reference range. There was
      no significant effect of diet on any other measured parameter. CONCLUSIONS AND
      CLINICAL RELEVANCE: Short-term administration of dietary soy has a measurable
      although modest effect on thyroid hormone homeostasis in cats. Increase in T4
      concentration relative to T3 concentration may result from inhibition of 5'
      iodothyronine deiodinase or enhanced T3 clearance. Soy is a common dietary
      component that increases serum T4 concentration in cats.

PMID- 15141878
TI  - Identification and concentration of soy phytoestrogens in commercial dog foods.
AB  - OBJECTIVE: To identify and determine the concentrations of phytoestrogens in
      commercial dog foods. SAMPLE POPULATION: 24 commercial dog foods, including 12
      moist or dry extruded commercial dog foods that contained soybeans or soybean
      fractions and 12 foods without any soybean-related ingredients listed on the
      label. PROCEDURE: Foods were analyzed for phytoestrogen content, including 4
      isoflavones (genistein, glycitein, daidzein, and biochanin A), 1 coumestan
      (coumestrol), and 2 lignans (secoisolariciresinol and matairesinol) by use of
      acid-methanol hydrolysis and high-pressure liquid chromatography with UV
      absorbance detection. Phytoestrogens were identified and quantified by reference
      to authentic standards. RESULTS: Isoflavones, coumestans, and lignans were
      undetectable in diets that did not list soybean-related ingredients on the label.
      Only 1 of the 12 diets that included soybean or soybean fractions had
      undetectable concentrations of phytoestrogens and that product contained soy
      fiber. The major phytoestrogens were the isoflavones daidzein (24 to 615 microg/g
      of dry matter) and genistein (4 to 238 microg/g of dry matter). CONCLUSIONS AND
      CLINICAL RELEVANCE: Soybean and soybean fractions are commonly used ingredients
      in commercial dog foods. Dietary intake of phytoestrogens may have both
      beneficial and deleterious health effects. Our results indicated that certain
      commercial dog foods contain phytoestrogens in amounts that could have biological
      effects when ingested long-term.

PMID- 15141879
TI  - Comparison of abomasal luminal gas pressure and volume and perfusion of the
      abomasum in dairy cows with left displaced abomasum or abomasal volvulus.
AB  - OBJECTIVE: To compare abomasal luminal gas pressure and volume and perfusion of
      the abomasum in dairy cows with a left displaced abomasum (LDA) or abomasal
      volvulus (AV). ANIMALS: 40 lactating dairy cows (25 with an LDA and 15 with an
      AV). PROCEDURE: Abomasal luminal gas pressure and volume and pulse oximetry
      values for the caudal portion of the dorsal ruminal sac and abomasal wall were
      measured during laparotomy. Abomasal perfusion was assessed on the basis of
      abomasal O2 saturation (pulse oximetry) before correction of the LDA or AV.
      Abomasal perfusion was also assessed after correction of the LDA or AV by
      measuring venous O2 saturation in the right gastroepiploic vein and calculating
      the abomasal oxygen-extraction ratio. RESULTS: Abomasal luminal gas pressure and
      volume were higher in cattle with an AV than in cattle with an LDA. Abomasal O2
      saturation was lower and abomasal oxygen-extraction ratio higher in cattle with
      an AV, compared with values in cattle with an LDA. In cows with an AV, lactate
      concentration in the gastroepiploic vein was greater than that in a jugular vein,
      whereas no difference in lactate concentrations was detected in cows with an LDA.
      Abomasal luminal gas pressure was positively correlated (r, 0.51) with plasma
      lactate concentration in the gastroepiploic vein and negatively correlated (r, 
      0.32) with abomasal O2 saturation determined by use of pulse oximetry.
      CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal perfusion decreases as luminal
      pressure increases in cattle with an AV or LDA.

PMID- 15141880
TI  - Assessment of cellular, biochemical, and histologic effects of bipolar
      radiofrequency treatment of canine articular cartilage.
AB  - OBJECTIVE: To assess the cellular, biochemical, and histologic effects of bipolar
      radiofrequency-generated heat on canine articular cartilage. SAMPLE POPULATION:
      Articular cartilage explants (n = 72) from 6 canine cadavers and cultured
      articular chondrocytes from 5 canine cadavers. PROCEDURE: Cartilage explants were
      randomly assigned to receive no treatment or treatment with focal (3 seconds) or
      diffuse bipolar radiofrequency. Following treatment, methylene blue permeability
      assay was performed (n = 12) and remaining samples (60) were cultured.
      Immediately and 5, 10, and 20 days after treatment, cultured explants were
      assessed for glycosaminoglycan (GAG) and collagen contents, type II collagen and
      matrix metalloproteinase (MMP)-13 immunoreactivity, and modified Mankin
      histologic scores. Liquid culture media were collected every 4 days and GAG
      content measured. Additionally, cultured chondrocytes were exposed for 3 seconds
      to media preheated to 37 degrees, 45 degrees, or 55 degrees C. Cell viability was
      determined via 2 different assays immediately and 24 hours after treatment.
      RESULTS: Radiofrequency-treated cartilage had reduced permeability and
      considerable histologic damage, compared with control samples; most treated
      samples had reduced collagen II staining and increased MMP-13 immunostaining.
      Compared with other treatments, less GAGs were released from cartilage after
      diffuse radiofrequency treatment throughout the study period. Cell viability was
      significantly different between controls and cells treated at 55 degrees C
      immediately and 24 hours after heat treatment. CONCLUSIONS AND CLINICAL
      RELEVANCE: In this study, bipolar radiofrequency treatment had detrimental
      effects on normal articular cartilage cells and extracellular matrix with
      probable long-term clinical consequences. The usefulness of radiofrequency for
      treatment of osteoarthritic articular cartilage requires further investigation.

PMID- 15141881
TI  - Effect of danofloxacin and tilmicosin on body temperatures of beef calves with
      pneumonia experimentally induced by inoculation with Mannheimia haemolytica.
AB  - OBJECTIVE: To examine effects of danofloxacin and tilmicosin on continuously
      recorded body temperature in beef calves with pneumonia experimentally induced by
      inoculation of Mannheimia haemolytica. ANIMALS: 41 Angus-cross heifers (body
      weight, 160 to 220 kg) without a recent history of respiratory tract disease or
      antimicrobial treatment, all from a single ranch. PROCEDURE: Radiotransmitters
      were implanted intravaginally in each calf. Pneumonia was induced
      intrabronchially by use of logarithmic-phase cultures of M. haemolytica. At 21
      hours after inoculation, calves were treated with saline (0.9% NaCl) solution,
      danofloxacin, or tilmicosin. Body temperature was monitored from 66 hours before
      inoculation until 72 hours after treatment. Area under the curve (AUC) of the
      temperature-time plot and mean temperature were calculated for 3-hour intervals
      and compared among treatment groups. RESULTS: The AUCs for 3-hour intervals did
      not differ significantly among treatment groups for any of the time periods.
      Analysis of the mean temperature for 3-hour intervals revealed significantly
      higher temperatures at most time periods for saline-treated calves, compared with
      temperatures for antimicrobial-treated calves; however, we did not detect
      significant differences between the danofloxacin- and tilmicosin-treated calves.
      The circadian rhythm of temperatures before exposure was detected again
      approximately 48 hours after bacterial inoculation. CONCLUSIONS AND CLINICAL
      RELEVANCE: Danofloxacin and tilmicosin did not differ in their effect on mean
      body temperature for 3-hour intervals but significantly decreased body
      temperature, compared with body temperature in saline-treated calves. Normal
      daily variation in body temperature must be considered in the face of respiratory
      tract disease during clinical evaluation of feedlot cattle.

PMID- 15141882
TI  - Evaluation of serum values of pancreatic enzymes after endoscopic retrograde
      pancreatography in dogs.
AB  - OBJECTIVE: To assess the safety of endoscopic retrograde pancreatography (ERP) in
      dogs by performing repeated clinical examinations and laboratory analyses of
      serum amylase, lipase, canine trypsin-like immunoreactivity (cTLI), and canine
      pancreatic elastase 1 (cE1) after the procedure. ANIMALS: 7 healthy Beagles.
      PROCEDURES: Clinical examinations were performed and blood samples obtained for
      serum enzyme determinations before and at intervals (10 minutes; 2, 4, and 6
      hours; and 1, 2, and 3 days) after ERP. RESULTS: Repeated clinical examinations
      revealed no signs of ERP-induced complications in the 7 dogs. Results of repeated
      laboratory tests indicated a transient increase in serum values of amylase,
      lipase, and cTLI but not cE1. Mean +/- SD lipase activity increased from 120.7 +/
      116.4 U/L to 423.4 +/- 243.1 U/L at 4 hours after ERP. Median serum cTLI
      concentration increased from 16.2 microg/L (range, 77 to 26.5 microg/L) to 34.9
      microg/L (range, 16.6 to 68.3 microg/L) 10 minutes after ERP. Enzyme values
      returned to baseline levels at the latest on day 2 in 6 of 7 dogs. Highest values
      for serum amylase, lipase, and cTLI and their delayed return to baseline values
      were detected in 1 dog with contrast filling of the pancreatic parenchyma.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ERP appears to be a
      safe imaging technique of pancreatic ducts in healthy dogs, although it induced a
      transient increase in serum values of pancreatic enzymes. In dogs, repeated
      clinical examinations and serum enzyme determinations can be used to monitor ERP
      induced complications such as acute pancreatitis.

PMID- 15141883
TI  - Effects of dietary sodium chloride intake on renal function and blood pressure in
      cats with normal and reduced renal function.
AB  - OBJECTIVE: To determine effects of variations in dietary intake of sodium
      chloride (NaCl) on systemic arterial blood pressure (ABP) in cats with normal and
      reduced renal function. ANIMALS: 21 adult cats (7 with intact kidneys [control
      cats; group C], 7 with unilateral renal infarction with contralateral nephrectomy
      [remnant-kidney model; group RK], and 7 with unilateral renal infarction and
      contralateral renal wrapping and concurrent oral administration of amlodipine
      [remnant-wrap model; group WA]). PROCEDURE: All cats were sequentially fed 3
      diets that differed only in NaCl content (50, 100, or 200 mg of Na/kg); each diet
      was fed for 7 days. The ABP was recorded continuously by radiotelemetry, and
      renal function (glomerular filtration rate [GFR]) was determined on the sixth day
      of each feeding period. RESULTS: Dietary supplementation with NaCl did not affect
      ABP, but it increased GFR in groups C and WA. The renin-angiotensin-aldosterone
      axis was activated in groups RK and WA at the lowest NaCl intake, but
      supplementation with NaCl suppressed this activation in group WA. The lowest NaCl
      intake was associated with hypokalemia and a high fractional excretion of
      potassium that decreased in response to supplementation with NaCl. Arterial
      baroreceptor resetting was evident after chronic hypertension but was not
      modified by dietary supplementation with NaCl. CONCLUSIONS AND CLINICAL
      RELEVANCE: Low NaCl intake was associated with inappropriate kaliuresis, reduced
      GFR, and activation of the renin-angiotensin-aldosterone axis without evidence of
      a beneficial effect on ABP. Therefore, this common dietary maneuver could
      contribute to hypokalemic nephropathy and progressive renal injury in cats.

PMID- 15141884
TI  - Determination of specific receptor sites for platelet activating factor in bovine
      neutrophils.
AB  - OBJECTIVE: To identify and characterize a platelet activating factor (PAF)
      receptor in bovine neutrophils by use of radioligand binding, reverse
      transcription-polymerase chain reaction (RT-PCR) assay, and western blot
      analysis. ANIMALS: 4 healthy adult cows. PROCEDURE: Bovine neutrophil membranes
      were isolated for association, dissociation, and saturation binding experiments
      with PAF labeled with hydrogen 3 (3H-PAF). The RT-PCR assay was performed with
      appropriate human primers, and western blot analysis was developed with a
      polyclonal antibody obtained from a peptide of bovine PAF receptor. RESULTS:
      Analysis of kinetic binding data supported a single class of PAF receptor.
      Binding of 3H-PAF to membrane preparations was selectively displaced by PAF and a
      nonhydrolyzable analogue of guanine triphosphate (Gpp[NH]p) and by lyso-PAF (a
      biologically inactive analogue of PAF) to a lesser extent. Among other PAF
      receptor antagonists, 14-deoxyandrographolide and WEB 2086 were the most
      effective in inhibiting 3H-PAF binding sites in neutrophil membranes; 2 lignans,
      schisandrin-A and gamma-schisandrin were also effective, but 2 gingkolides
      (BN52020 and BN52021) only mildly inhibited 3H-PAF binding. Results of RT-PCR
      assay and western blot analysis of neutrophil crude membranes confirmed the
      presence of a PAF receptor. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated
      that bovine neutrophils express only 1 type of PAF receptor, and it is likely
      that this receptor is involved in inflammatory responses. The most effective PAF
      antagonists were 14-deoxyandrographolide and WEB 2086; these PAF antagonists may
      be potentially useful in the treatment of inflammatory processes in cattle.

PMID- 15141885
TI  - Effect of carboxymethylcellulose and hyaluronate solutions on jejunal healing in
      horses.
AB  - OBJECTIVE: To compare a double-layer inverting anastomosis with a single-layer
      appositional anastomosis, coated with either 1% sodium carboxymethylcellulose
      (SCMC) or 0.4% sodium hyaluronate (HA) solutions, in the small intestine of
      horses with respect to anastomotic healing and adhesion formation. ANIMALS: 18
      adult horses. PROCEDURE: Midline celiotomy and end-to-end jejunal anastomoses
      were performed. In control group horses (n = 6), a double-layer inverting
      anastomosis coated with sterile lactated Ringer's solution was performed. In
      treatment group horses, a single-layer appositional anastomosis was performed
      that was coated with 1% carboxymethylcellulose solution (SAA + SCMC group horses,
      6) or 0.4% hyaluronate solution (SAA + HA group horses, 6). An additional 500 mL
      of the respective treatment solution was applied to the jejunal serosal surface,
      and 2 jejunal serosal abrasion sites were created. Horses were euthanatized 10
      days after surgery. Anastomoses and abdominal adhesions were evaluated grossly.
      Anastomotic healing was evaluated on the basis of bursting wall tension. RESULTS:
      Bursting wall tension was significantly greater in SAA + SCMC group horses,
      compared with control group horses. All intestinal segments failed at a point
      distant to the anastomosis. Significantly fewer adhesions were found at the
      abrasion sites of SAA + HA group horses, compared with control group horses. No
      differences were found in adhesion formation at the anastomotic sites among
      groups. CONCLUSIONS AND CLINICAL RELEVANCE: Coating a single-layer appositional
      jejunal anastomosis with SCMC or HA solutions does not adversely affect
      anastomotic healing. Application of 0.4% HA solution to the serosal surface of
      the jejunum significantly decreases the incidence of experimentally induced intra
      abdominal adhesion formation in horses.

PMID- 15141886
TI  - Pathologic changes associated with brucellosis experimentally induced by aerosol
      exposure in rhesus macaques (Macaca mulatta).
AB  - OBJECTIVE: To develop an aerosol exposure method for induction of brucellosis in
      rhesus macaques (Macaca mulatta). ANIMALS: 10 adult rhesus macaques. PROCEDURE: 8
      rhesus macaques were challenge exposed with 10(2) to 10(5) colony-forming units
      of Brucella melitensis 16M by use of an aerosol-exposure technique, and 2 served
      as control animals. All macaques were euthanatized 63 days after challenge
      exposure. Gross and microscopic lesions, bacterial burden in target organs, and
      histologic changes in tissues were evaluated. RESULTS: Grossly, spleen weights
      were increased in exposed macaques, compared with spleen weights in control
      macaques. Histologically, there was inflammation in the liver, kidneys, spleen,
      testes, and epididymides in exposed macaques. The spleen and lymph nodes had
      increased numbers of lymphohistiocytic cells. Morphometrically, the spleen also
      had an increased ratio of white pulp to red pulp. Areas of hepatitis and amount
      of splenic white pulp increased with increasing exposure dose. CONCLUSIONS AND
      CLINICAL RELEVANCE: Pathologic findings in rhesus macaques after aerosol exposure
      to B melitensis are similar to those observed in humans with brucellosis. IMPACT
      FOR HUMAN MEDICINE: These results may aid in the development of a vaccine against
      brucellosis that can be used in humans.

PMID- 15141887
TI  - Effect of sevoflurane on hemodynamic and cardiac energetic parameters in ferrets.
AB  - OBJECTIVE: To determine the effect of sevoflurane on cardiac energetic and
      hemodynamic parameters in ferrets. ANIMALS: 7 healthy domesticated ferrets.
      PROCEDURE: Sevoflurane was used as the sole anesthetic agent for general
      anesthesia in ferrets. Standard midline laparotomy and median sternotomy were
      performed to permit instrumentation. Myocardial blood flow was determined by use
      of colored microsphere technology. Measurements and blood samples were obtained
      at 1.25%, 2.5%, and 3.75% expired concentration of sevoflurane. RESULTS: A dose
      dependent decrease in arterial blood pressure, left ventricular pressure,
      systemic vascular resistance, aortic flow, and dp/dt (an index of contractility)
      was detected as expired concentration of sevoflurane increased. Heart rate,
      central venous pressure, coronary vascular resistance, myocardial oxygen
      extraction ratio, and tau (the time constant of relaxation) were unchanged.
      Cardiac external work decreased, as did myocardial oxygen consumption, causing
      increased cardiac efficiency at higher concentrations of sevoflurane. CONCLUSIONS
      AND CLINICAL RELEVANCE: Sevoflurane caused minimal and predictable cardiovascular
      effects in ferrets without increasing myocardial metabolic demands. Data obtained
      from this study have not been previously reported for a species that is being
      commonly used in cardiovascular research. These findings also support use of
      sevoflurane as a safe inhalant anesthetic in ferrets for clinical and research
      settings.

PMID- 15141888
TI  - Effect of thalidomide on growth and metastasis of canine osteosarcoma cells after
      xenotransplantation in athymic mice.
AB  - OBJECTIVE: To determine whether thalidomide inhibits the growth of primary and
      pulmonary metastatic canine osteosarcoma in mice after xenotransplantation.
      ANIMALS: Athymic nude mice. PROCEDURE: Canine osteosarcoma cells were injected SC
      in 50 mice. Mice were randomly placed into the following groups: control group (n
      = 13; DMSO [drug vehicle] alone [0.1 mL/d, IP]); low-dose group (12; thalidomide
      [100 mg/kg, IP]), mid-dose group (13; thalidomide [200 mg/kg, IP]); and high-dose
      group (12; thalidomide [400 mg/kg, IP]). Starting on day 8, treatments were
      administered daily and tumor measurements were performed for 20 days. On day 28,
      mice were euthanatized and primary tumors were weighed. Lungs were examined
      histologically to determine the number of mice with metastasis and tumor emboli.
      Mean area of the pulmonary micrometastatic foci was determined for mice from each
      group. RESULTS: Primary tumor size and weight were not significantly different
      among groups. The number of mice in the mid-dose (200 mg/kg) and high-dose (400
      mg/kg) groups with micrometastasis was significantly less than the number of
      control group mice; however, the number of mice with tumor emboli was not
      affected by thalidomide treatment. Size of micrometastasis lesions was not
      affected by thalidomide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Mean area
      of micrometastases was not affected by treatment; however, growth of
      micrometastases had not yet reached an angiogenesis-dependent size. Although
      thalidomide did not affect growth of primary tumors in mice after
      xenotransplantation of canine osteosarcoma cells, our findings indicate that
      thalidomide may interfere with the ability of embolic tumor cells to complete the
      metastatic process within the lungs.

PMID- 15141889
TI  - Evaluation of a sensor-based system of motion analysis for detection and
      quantification of forelimb and hind limb lameness in horses.
AB  - OBJECTIVE: To compare a sensor-based accelerometer-gyroscopic (A-G) system with a
      video-based motion analysis system (VMAS) technique for detection and
      quantification of lameness in horses. ANIMALS: 8 adult horses. PROCEDURE: 2
      horses were evaluated once, 2 had navicular disease and were evaluated before and
      after nerve blocks, and 4 had 2 levels of shoe-induced lameness, alternatively,
      in each of 4 limbs. Horses were instrumented with an accelerometer transducer on
      the head and pelvis, a gyroscopic transducer on the right forelimb and hind feet,
      and a receiver-transmitter. Signals from the A-G system were collected
      simultaneously with those from the VMAS for collection of head, pelvis, and right
      feet positions with horses trotting on a treadmill. Lameness was detected with an
      algorithm that quantified lameness as asymmetry of head and pelvic movements.
      Comparisons between the A-G and VMAS systems were made by use of correlation and
      agreement (kappa value) analyses. RESULTS: Correlation between the A-G and VMAS
      systems for quantification of lameness was linear and high (r2 = 0.9544 and
      0.8235 for forelimb and hind limb, respectively). Quantification of hind limb
      lameness with the A-G system was higher than measured via VMAS. Agreement between
      the 2 methods for detection of lameness was excellent (kappa = 0.76) for the
      forelimb and good (kappa = 0.56) for the hind limb. CONCLUSIONS AND CLINICAL
      RELEVANCE: The A-G system detected and quantified forelimb and hind limb lameness
      in horses trotting on the treadmill. Because the data are collected wirelessly,
      this system might be used to objectively evaluate lameness in the field.

PMID- 15141890
TI  - Assessment of the neurologic effects of dietary deficiencies of phenylalanine and
      tyrosine in cats.
AB  - OBJECTIVE: To determine the neurologic effects of reduced intake of phenylalanine
      and tyrosine in black-haired cats. ANIMALS: 53 specific pathogen-free black
      domestic shorthair cats. PROCEDURE: Cats were fed purified diets containing
      various concentrations of phenylalanine and tyrosine for < or = 9 months. Blood
      samples were obtained every 2 months for evaluation of serum aromatic amino acid
      concentrations. Cats were monitored for changes in hair color and neurologic or
      behavioral abnormalities. Three cats with neurologic deficits underwent clinical
      and electrophysiologic investigation; muscle and nerve biopsy specimens were also
      obtained from these cats. RESULTS: After 6 months, neurologic and behavioral
      abnormalities including vocalization and abnormal posture and gait were observed
      in cats that had received diets containing < 16 g of total aromatic amino acid/kg
      of diet. Electrophysiologic data and results of microscopic examination of muscle
      and nerve biopsy specimens from 3 cats with neurologic signs were consistent with
      sensory neuropathy with primary axonal degeneration. Changes in hair color were
      detected in cats from all groups receiving < 16 g of phenylalanine plus
      tyrosine/kg of diet. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that
      chronic dietary restriction of phenylalanine and tyrosine in cats may result in a
      predominantly sensory neuropathy. In cats, the long-term nutritional requirement
      for phenylalanine and tyrosine appears to be greater for normal neurologic
      function than that required in short-term growth experiments. Official present
      day recommendations for dietary phenylalanine and tyrosine in cats may be
      insufficient to support normal long-term neurologic function.

PMID- 15141891
TI  - Comparison of two laparoscopic treatments for experimentally induced abdominal
      adhesions in pony foals.
AB  - OBJECTIVE: To compare laparoscopic dissection with-laparoscopic dissection
      combined with abdominal instillation of ferric hyaluronate gel for the treatment
      of experimentally induced adhesions in pony foals. ANIMALS: 12 healthy pony
      foals. PROCEDURE: A serosal abrasion method was used to create adhesions at 4
      sites on the jejunum (day 0). At day 7 laparoscopy was performed and the
      adhesions observed in each foal were recorded. In group-1 foals (n = 6), the
      adhesions were separated laparoscopically (treatment 1). In group-2 foals (n =
      6), 300 mL of 0.5% ferric hyaluronate gel was infused into the abdomen after the
      adhesions were separated laparoscopically (treatment 2). At day 24, terminal
      laparoscopy was performed and the adhesions observed were recorded. Total number
      of adhesions within each group was compared between day 7 and 24. Data were
      analyzed to determine whether an association existed between the number of
      adhesions on day 24 and treatment type. RESULTS: At day 24, the number of
      adhesions was significantly decreased within each group, compared with the number
      of adhesions at day 7 (group-1 foals, 10 vs 22 adhesions; group-2 foals, 3 vs 20
      adhesions). Treatment 1 was associated with a significantly higher number of
      adhesions at day 24, compared with treatment 2 (odds ratio, 4.54; 95% confidence
      interval, 1.03 to 23.02). CONCLUSION AND CLINICAL RELEVANCE: Abdominal
      instillation of 0.5% ferric hyaluronate gel after laparoscopic dissection was a
      more effective technique than laparoscopic dissection alone to treat
      experimentally induced adhesions in pony foals. Laparoscopic adhesiolysis
      following abdominal surgery in foals is a safe and effective technique.

PMID- 15141892
TI  - Effects of feeding large amounts of grain on colonic contents and feces in
      horses.
AB  - OBJECTIVE: To assess changes in systemic hydration, concentrations of plasma
      electrolytes, hydration and physical properties of colonic contents and feces,
      and gastrointestinal transit in horses with access to large amounts of grain.
      ANIMALS: 6 horses with right dorsal colon (RDC) fistulas. PROCEDURE: In a
      crossover design, horses were alternately fed 1 of 3 diets: orchard grass hay ad
      libitum after being adapted to this diet for at least 5 days, orchard grass hay
      ad libitum and 4.55 kg of grain offered every 12 hours after being adapted to
      orchard grass hay ad libitum for at least 5 days, or orchard grass hay ad libitum
      and 4.55 kg of grain offered every 12 hours after being adapted to this diet for
      at least 5 days. Physical examinations were performed and samples of blood,
      colonic contents, and feces were collected every 6 hours during a 48-hour
      observation period. RESULTS: Grain ingestion had several effects, including
      changes in the concentrations of electrolytes in plasma; RDC contents became more
      homogenous, dehydrated, foamy, and less dense; RDC contents flowed spontaneously
      when the cannula was opened; RDC contents expanded when heated in an oven; and
      feces became fetid and less formed. Horses did not have any clinical signs of
      colic, endotoxemia, or laminitis. CONCLUSIONS AND CLINICAL RELEVANCE: Changes
      observed in the colonic contents and feces may be explained by the large amounts
      of hydrolyzable carbohydrates provided by grain. Access to large amounts of grain
      may increase the risk of tympany and displacement of the large intestine.

PMID- 15141893
TI  - Effects of enteral and intravenous fluid therapy, magnesium sulfate, and sodium
      sulfate on colonic contents and feces in horses.
AB  - OBJECTIVE: To assess changes in systemic hydration, concentrations of
      electrolytes in plasma, hydration of colonic contents and feces, and
      gastrointestinal transit in horses treated with IV fluid therapy or enteral
      administration of magnesium sulfate (MgSO4), sodium sulfate (NaSO4), water, or a
      balanced electrolyte solution. ANIMALS: 7 horses with fistulas in the right
      dorsal colon (RDC). PROCEDURE: In a crossover design, horses alternately received
      1 of 6 treatments: no treatment (control); IV fluid therapy with lactated
      Ringer's solution; or enteral administration of MgSO4, Na2SO4, water, or a
      balanced electrolyte solution via nasogastric intubation. Physical examinations
      were performed and samples of blood, RDC contents, and feces were collected every
      6 hours during the 48 hour-observation period. Horses were muzzled for the
      initial 24 hours but had access to water ad libitum. Horses had access to hay,
      salt, and water ad libitum for the last 24 hours. RESULTS: Enteral administration
      of a balanced electrolyte solution and Na2SO4 were the best treatments for
      promoting hydration of RDC contents, followed by water. Sodium sulfate was the
      best treatment for promoting fecal hydration, followed by MgSO4 and the balanced
      electrolyte solution. Sodium sulfate caused hypocalcemia and hypernatremia, and
      water caused hyponatremia. CONCLUSIONS AND CLINICAL RELEVANCE: Enteral
      administration of a balanced electrolyte solution promoted hydration of RDC
      contents and may be useful in horses with large colon impactions. Enteral
      administration of either Na2SO4 or water may promote hydration of RDC contents
      but can cause severe electrolyte imbalances.

PMID- 15141894
TI  - Influences of preschool policies and practices on children's physical activity.
AB  - The objective of this study was to determine if moderate to vigorous physical
      activity (MVPA) of 3-5 year old preschool children varied with differences in
      policies/practices, and overall quality of preschools. A total of 266 children
      (47% males, 60% African American) from 9 preschools were observed for 1 hour on 3
      different days. PA of children was observed twice per minute and scored as 1-5,
      with 1 for stationary/motionless and 5 for fast movement. Summary MVPA was
      calculated over the 3 days as percent of times observed at levels of 4 or 5, and
      percent of time at levels 1 or 2 as sedentary activity. A structured interview
      about PA policies was conducted with an administrator at each preschool and
      overall quality of the preschool was assessed using Early Childhood Environment
      Rating Scale-Revised Edition (ECERS-R). Preschools were divided into groups
      according to whether a specific policy/practice that would be logically
      hypothesized to promote PA was in place at the school. MVPA differences between
      groups of children was assessed using mixed ANOVA controlling for preschool. When
      preschools offered more field trips, and more college educated teachers, the
      children participated in more MVPA. Children who attended preschools with lower
      quality spent more time in sedentary activity. In conclusion, children in
      preschools which may have more resources and better quality appear to show both
      more sedentary behavior and more MVPA.

PMID- 15141895
TI  - Reducing the use of emergency medical resources among Head Start families: a
      pilot study.
AB  - The objective of this study was to determine whether self-care training with Head
      Start parents can improve their ability to manage the healthcare needs of their
      children measured by utilization of emergency department (ED) and physician
      services. Four hundred and six families in Head Start agencies were included in
      the study. Parents were given a low-literate self-help book entitled What To Do
      When Your Child Gets Sick. The study design included using multiple-choice, pre
      and post-intervention survey data. In a six month follow-up, parents who received
      the book reported a 48% reduction in ED visits and a 37.5% reduction in clinic
      visits. More research is needed to determine if this self-care tool and
      additional training can have a significant impact on inappropriate use of medical
      resources.

PMID- 15141896
TI  - Content analysis and key informant interviews to examine community response to
      the purchase, possession, and/or use of tobacco by minors.
AB  - The aim of this study was to identify and describe local ordinances in New Jersey
      that make it illegal for minors to purchase, possess, and/or use tobacco (PPU). A
      coding instrument was formulated and content analysis of each ordinance was
      conducted between March 1999 andJanuary 2002. Additionally, key informant
      interviews with community officials were conducted by telephone between September
      2000 and February 2002 to collect qualitative information on implementation and
      enforcement. Content analysis of identified ordinances assessed when the
      ordinance was enacted, specific laws and clauses included, enforcing party, area
      of jurisdiction, and penalties associated with a citation. Key informant
      interviews assessed the catalyst for enacting the ordinance, penalties,
      enforcement activity, and method of tracking citations. As of January 2002, 48
      municipalities in New Jersey had passed mandates banning minor purchase,
      possession, and/or use of tobacco. Of the 48 ordinances reviewed, 71% were passed
      during or after 1998. Nearly all of the ordinances (94%) included prohibited
      minor usage of tobacco, 77% prohibited minor possession of tobacco and 23%
      prohibited minor purchase of tobacco. In over 80% of communities, municipal
      police departments were responsible for enforcement. Two out of 35 communities
      reached for interview reported having a formal system for tracking enforcement or
      citations. The results illustrate that local PPU ordinances in New Jersey vary
      widely both in principle and in practice, suggesting that such ordinances may be
      too heterogeneous and lacking in cohesion to have any impact on youth smoking.

PMID- 15141897
TI  - A snapshot of substance abuse among homeless and runaway youth in Denver,
      Colorado.
AB  - We report on results of a one-day survey measuring rates of substance use and HIV
      risk behaviors among the homeless youth population of Denver, Colorado. On March
      15, 2001, staff of Urban Peak, conducted a single-day survey of homeless and
      runaway youth in the Denver metropolitan region, going to locations known to be
      frequented by this population. All youth encountered were asked to fill out a
      brief survey asking about past nine month use of the following substances:
      alcohol, marijuana, cocaine, methamphetamine, heroin, hallucinogens, ecstasy and
      ketamine, and HIV risk behaviors. Chi-square analyses of the association of
      substance used and gender, age, living situation, and ethnicity were conducted.
      In addition, the use of any club drug was examined. One-hundred-eighty-six
      homeless or runaway youth were surveyed; 74 percent were between 16 and 25. Rates
      of use over the last nine months were as follows: alcohol, 69 percent; marijuana,
      75 percent; methamphetamine, 18 percent; cocaine, 19 percent; heroin, 12 percent;
      hallucinogens, 30 percent; ecstasy, 25 percent; and ketamine, 13 percent. Eleven
      percent reported trading sex for drugs, money, food, or shelter; and 13 percent
      reported sharing needles. There were significant associations between living
      situation and use of marijuana, cocaine and hallucinogens. Prevalence rates of
      club drugs show 75 percent, 77 percent and 77 percent of homeless or runaway
      youth ihaving used ecstasy, ketamine and hallucinogens one to three times per
      month over the last nine months, respectively. Prevalence rates of substance use
      among homeless youth in the Denver metropolitan are similar to rates reported in
      other larger metropolitan areas. Routine screening for every substance needs to
      be part of the assessment for all homeless youth. Initial data points to a need
      for more research exploring protective factors among this population and to
      better understand the prevalence of club drug use.

PMID- 15141898
TI  - Pesticide sales in low-income, minority neighborhoods.
AB  - The US EPA has phased-out residential use of two organophosphate pesticides
      commonly used to control cockroaches-retail sales of chlorpyrifos were scheduled
      to end on 12/31/01, and diazinon on 12/31/02. In light of recent findings
      highlighting the associations between pests, pesticides and health, we surveyed
      stores in low-income, minority neighborhoods in New York City to determine
      whether the phase-outs have been effective and to assess the availability of
      alternatives to spray pesticides. In summer 2002, when sales of chlorpyrifos were
      illegal and diazinon still legal, we surveyed 106 stores selling pesticides. Four
      percent sold products containing chlorpyrifos and 40 percent sold products
      containing diazinon. One year later, when sales of both pesticides were to have
      ended, we surveyed 109 stores selling pesticides in the same neighborhoods and
      found chlorpyrifos in only one store and diazinon in 18 percent of stores,
      including 80 percent of supermarkets surveyed. At least one form of lower
      toxicity pesticides, including gels, bait stations and boric acid was available
      in 69 percent of stores in 2002. However sprays were most widely available, found
      in 94 percent of stores in 2002 and less expensive than lower toxicity baits and
      gels. In a separate survey of storekeeper recommendations conducted in 2002,
      storekeepers recommended lower toxicity pesticides as the best way to control
      cockroaches 79% of the time. The EPA's phase-outs have nearly eliminated sales of
      chlorpyrifos, but the diazinon phase-out appears to be less effective.

PMID- 15141899
TI  - Concerns about infectious hepatitis and Delacorte's Welfare Island Fountain.
AB  - In 1969, philanthropist George T. Delacorte donated a spectacular water fountain
      to New York City on the southern tip of Welfare Island. Architects designed the
      fountain's jet geyser to pump a plume of water from the East River more than 400
      feet into the air. Public health experts feared that the water from the heavily
      polluted East River could be a possible source for the spread of infectious
      hepatitis. Water droplets could be airborne by the prevailing winds to land on
      the densely populated east side of Manhattan. Upon the insistence of the New York
      City Department of Health, the fountain's water intake source was chlorinated.
      This action was initiated before the discovery of the hepatitis A virus (HAV) in
      1973. A miscellany of continuing problems plagued the fountain for about two
      decades, causing the donor to label the fountain "Delacorte's Folly." Eventually,
      Delacorte gave up. In the late 1980s, the fountain ceased spouting and was
      finally dismantled.

PMID- 15141901
TI  - Corsi's block-tapping test: some characteristics of the spatial path which
      influence memory.
AB  - By using a sequence of digits it is possible to indicate the path of Corsi's
      block-tapping test by drawing a line to join the central points of the cubes
      which make up the sequence. By doing this one can analyze the sequence of digits
      according to quantitative parameters. There were three characteristics of the
      spatial path taken into consideration in this research: the number of cubes which
      constitute a series of digits, the number of times the path intersected itself,
      and the length of the path measured in millimeters. The experiment, carried out
      with 70 university students, showed that all three factors were significant on
      analysis of variance, and also that there were differences between the sexes, the
      men performing better. No interactions were significant. Despite this, additional
      significant differences were found among the series with the same number of
      cubes, intersections, and length, meaning that other variables influence the
      difficulty of the spatial path.

PMID- 15141900
TI  - Expertise and peripheral autonomic activity during the preparation phase in
      shooting events.
AB  - This study compared effectiveness of the concentration period in two groups of
      shooters to evaluate the influence of their expertise while concentrating on the
      target. Marksmen (pistol shooters, 10 men and 5 women) and pentathletes (6 men
      and 7 women) took part in a shooting competition in keeping with the rules of
      each event. Participants were then asked to imagine themselves shooting, at the
      laboratory. Five variables representing the activity of the autonomic nervous
      system were continuously recorded (skin resistance and potential, skin blood
      flow, skin temperature, instantaneous heart rate). Autonomic responses recorded
      during concentration, actual shooting, and mental imagery were compared by
      calculating the ratios concentration/ shooting and imagery/shooting. The
      resultant mean ratio was used to characterize each participant. The same
      autonomic nervous system pattern was observed during concentrating on the target,
      mental imagery, and actual shooting. However, marksmen showed ratios closer to
      1.0 than pentathletes, absolute mean differences being .06 and .3, respectively.
      Shorter duration and weakest amplitude responses were recorded during the
      concentration phase in the Pentathlete group, suggesting that they have more
      difficulty in using mental imagery during competition than marksmen. When
      subjects performed well, a specific response pattern was observed in the Marksman
      group, but not in the Pentathlete group, except in skin potential. In both
      Marksman and Pentathlete groups, a majority of negative skin potential responses
      were found in the concentration and shooting phases for the best shots.

PMID- 15141902
TI  - The Mozart effect: questions about the seminal findings of Rauscher, Shaw, and
      colleagues.
AB  - Seminal evidence for the Mozart effect was presented by Rauscher, Shaw, and
      colleagues in 1993 and 1994. A critical evaluation of their methodologies and
      interpretation of findings raises questions that must be answered before this
      evidence can be regarded as valid. We discuss issues such as their scoring of the
      Stanford-Binet Intelligence Scale, the experimental design used in their 1993
      study, the validity of their 1993 IQ measure, the duration of the Mozart effect,
      their choice of experimental tasks in relation to predictions of the trion model
      of neural functioning, and the statistical analyses and interpretation of results
      in the 1993 and 1994 studies.

PMID- 15141903
TI  - Relationship between physical education students' achievements in a French
      badminton service test and expert ratings of technique quality.
AB  - Assessment of practical skills in physical education lessons have often been
      criticised as subjective. In this study three experienced judges' ratings poorly
      predicted the 116 students' scores on the French badminton short service test.

PMID- 15141904
TI  - Influence of cup stacking on hand-eye coordination and reaction time of second
      grade students.
AB  - Cup stacking has been adopted recently by many physical education programs to
      enhance rudimentary motor skills such as hand-eye coordination and ambidexterity
      as well as quickness and concentration; however, no empirical evidence has been
      published to support these claims. We examined the influence of cup stacking on
      hand-eye coordination and reaction time of 24 boys and 18 girls in second grade
      as measured by the Soda Pop and Yardstick tests, respectively. Two physical
      education classes were randomly assigned as treatment and control groups and were
      pre- and posttested for hand-eye coordination and reaction time. The treatment
      group participated in a 5-wk. cup-stacking program. Significant improvements were
      noted for both hand-eye coordination and reaction time between the pre- and
      posttest scores for this group but not for the control group. Therefore, cup
      stacking is indeed effective in enhancing hand-eye coordination and reaction
      time.

PMID- 15141905
TI  - Unipodal performance and leg muscle mass in jumping skills among ballet dancers.
AB  - We examined the vertical jump performance of each leg among 10 right-footed
      female ballet dancers with 1 yr. of international professional experience
      (quadrilles: Opera ballerinas). Their mean age was 17.5 yr. (SD=0.3). The maximal
      height of the unilateral jump was recorded, and muscle mass was evaluated by
      biphotonic absorptiometry method. Muscle mass and maximal jump height were
      similar for the two legs. A strong inverse relation was found between the muscle
      mass of the right leg (67%) and maximal jump height (r=-.81, p<.01) but not for
      the left leg. These results highlight a functional asymmetry and the effect of
      motor laterality in dance.

PMID- 15141906
TI  - Evaluating effects in short time series: alternative models of analysis.
AB  - In the applied context, short time-series designs are suitable to evaluate a
      treatment effect. These designs present serious problems given autocorrelation
      among data and the small number of observations involved. This paper describes
      analytic procedures that have been applied to data from short time series, and an
      alternative which is a new version of the generalized least squares method to
      simplify estimation of the error covariance matrix. Using the results of a
      simulation study and assuming a stationary first-order autoregressive model, it
      is proposed that the original observations and the design matrix be transformed
      by means of the square root or Cholesky factor of the inverse of the covariance
      matrix. This provides a solution to the problem of estimating the parameters of
      the error covariance matrix. Finally, the results of the simulation study
      obtained using the proposed generalized least squares method are compared with
      those obtained by the ordinary least squares approach. The probability of Type I
      error associated with the proposed method is close to the nominal value for all
      values of rho1 and n investigated, especially for positive values of rho1. The
      proposed generalized least squares method corrects the effect of autocorrelation
      on the test's power.

PMID- 15141907
TI  - Coping skills: role of trait sport confidence and trait anxiety.
AB  - The current research assesses relationships among coping skills, trait sport
      confidence, and trait anxiety. Two samples (n=47 and n=77) of international
      competitors from surf life saving (M=23.7 yr.) and touch rugby (M=26.2 yr.)
      completed the Athletic Coping Skills Inventory, Trait Sport Confidence Inventory,
      and Sport Anxiety Scale. Analysis yielded significant correlations amongst trait
      anxiety, sport confidence, and coping. Specifically confidence scores were
      positively associated with coping with adversity scores and anxiety scores were
      negatively associated. These findings support the inclusion of the personality
      characteristics of confidence and anxiety within the coping model presented by
      Hardy, Jones, and Gould, Researchers should be aware that confidence and anxiety
      may influence the coping processes of athletes.

PMID- 15141908
TI  - Cognitive and somatic anxiety and self-confidence in athletic performance of
      beach volleyball.
AB  - This study considered the influence of competitive anxiety and self-confidence
      state responses upon athletic performance. 66 male beach volleyball players
      completed the translated and modified Competitive State Anxiety Inventory-2 which
      included the original intensity scale and a direction scale of Jones and Swain.
      Players' performance was scored from the video records using a standard rating
      scales. Correlations indicated scores on Direction subscale of modified
      Competitive State Anxiety Inventory-2 and Self-confidence were moderately
      positively (r=.27 to .51) correlated with different skill components and sum of
      skill components of beach volleyball. Stepwise multiple regressions indicated
      that, as anticipated, directional perceptions of cognitive and somatic anxiety
      and self-confidence were significant predictors of beach volleyball performance
      but accounted for only 42% of variance. Original Intensity subscales of somatic
      and cognitive anxiety did not predict performance. Findings support the notion
      that direction of anxiety responses must be taken into consideration when
      examining anxiety-performance association in sport.

PMID- 15141909
TI  - Further investigation of harmonic priming in long contexts using musical timbre
      as surface marker to control for temporal effects.
AB  - Harmonic priming studies have reported facilitated processing for chords that are
      harmonically related to the prime context. Responses to the target (the last
      chord of an 8-chord sequence) were faster and more accurate when the target was
      strongly related, i.e., a tonic chord, to the preceding prime context than when
      it was less related, i.e., a subdominant chord. Results have been interpreted in
      terms of musical expectations and processing speed: the prime allows listeners to
      develop expectations for future events which lead to facilitated processing of
      the most strongly expected event. The present experiment investigated an
      alternative hypothesis suggesting that the harmonic structure of the prime
      context might create an ambiguity about "when" to respond that is stronger in
      contexts ending on less related targets than in contexts ending on strongly
      related targets. A change of musical timbre was used as surface marker indicating
      without ambiguity the temporal occurrence of the target. Participants made
      speeded intonation judgments of the target, i.e., judging whether targets are
      acoustically consonant or dissonant. The findings replicate the previously
      reported priming effect and rule out that processing differences are solely due
      to ambiguities about when in time the target will occur.

PMID- 15141910
TI  - Assessing a new response-microswitch combination with a boy with minimal motor
      behavior.
AB  - This study assessed whether a boy with profound multiple disabilities and minimal
      motor behavior could learn to use a new response-microswitch combination to
      control environmental stimulation. The response selected was a chin movement; a
      mechanical microswitch was set up for this response. The boy learned to use the
      microswitch, increasing the frequency of the chin response and the level of
      pleasant stimulation following such response. The performance was retained at a 2
      mo. post-intervention check.

PMID- 15141911
TI  - Comparison of blinking behavior during listening to and speaking in Japanese and
      English.
AB  - Blinking behavior during conversation may be different between conditions in
      listening and responding to questions because sifting attention from external to
      internal is possibly associated. The purpose of this study was to compare
      blinking behavior, duration, heart rates, and mental states during the tasks of
      listening to and responding to questions in Japanese and English. Participants
      were 67 (35 men and 32 women) undergraduate students. Blink rate while responding
      to questions in English did not differ from that while responding to questions in
      Japanese, but blink rate while listening to questions in English was
      significantly reduced compared to that while listening to Japanese. While anxiety
      and uneasiness were increased by the English conversation, blink rate and heart
      rate were decreased. Blinking behavior may be related to thinking and attention.

PMID- 15141912
TI  - Perceptions of body image among Japanese and Croatian children of preschool age.
AB  - This study examined the differences in current and ideal body size among 108
      Japanese and 129 Croatian preschool children (M=4.9 yr.). Boys and girls in both
      samples showed similarities by selecting the figure representing their current
      body size. Significant sex differences were found in selection of an ideal figure
      in the Japanese sample but not in the Croatian group. Japanese girls showed
      greater preference for a thinner figure than boys. In selection of an ideal body
      size significant cultural differences were found only for boys: Japanese boys
      preferred thinner figures. Results relating to body discrepancy (Current minus
      Ideal figures) indicated that there were fewer satisfied Japanese girls than
      Croatian girls whereas for the boys, a significantly larger number of Japanese
      than Croatian boys wished to be heavier.

PMID- 15141913
TI  - Relationships of coping styles with type of sport.
AB  - The purpose of this study was to ascertain whether the type of sport is
      associated with coping styles. 80 athletes (weightlifters, runners, swimmers, and
      triathletes) were administered the Coping Inventory for Stressful Situations.
      Analysis showed weightlifters had a lower mean score on Avoidance coping than the
      other groups of athletes. Differences concerning sex and ability were found as
      well.

PMID- 15141914
TI  - Evaluation of empirical methods and methodological foundations of human left
      handedness.
AB  - The methodological and empirical foundations underlying the theories on human
      left-handedness are examined, including the definition and classification of left
      handedness, its relation to pathology, and the results on family, adoption, and
      twin research. It is argued that major research findings on left-handedness are
      based on inadequate empirical methods, and the concrete definitions and
      assessment procedures do not meet validity and reliability criteria. This also
      casts doubt on the relationship between left-handedness and pathology reported in
      the literature. Furthermore, findings from family, adoption, and twin studies do
      not allow interpretation of possible direct genetic contributions to explaining
      left-handedness. It is concluded that the methodological limitations of a causal
      explanation should encourage an examination of the epistemological and
      methodological premises of theory formulation. The functional method and a
      theoretical framework based on early childhood experiences and the neural
      plasticity of the brain may be more appropriate for the selection of empirical
      methods in research of human left-handedness.

PMID- 15141915
TI  - Relations between the inflection point on the force-time curve and force-time
      parameters during static explosive grip.
AB  - Individual differences in muscle contractile speed during static explosive muscle
      contraction are reflected in the developmental phase of the force-time curve. The
      purposes of this study were to clarify the properties and reliability of the
      inflection point of force-time, statistically dividing speed during static
      explosive grip into two phases and to assess the relations between that
      inflection point and others. Static explosive grip data were measured two times
      with a 5-min. rest (sampling frequency; 100 Hz). 32 healthy, young men (age: 15.5
      +/- 0.8 yr., height: 173.9 +/- 7.3 cm, body mass: 71.5 +/- 11.2 kg) participated.
      8 static explosive grip parameters were selected: time of reaching, integrated
      area, and quotient values of the integrated areas up to 0.25, 0.5, and 1.0 sec.
      divided by maximal grip force. The inflection point was calculated statistically
      from two regression lines fitted to a developmental phase and the almost steady
      state phase of reaching maximal grip force by applying a two-phase regression
      model. The reliabilities of maximal grip force, time of reaching 90% of maximal
      grip force, and the integrated area until 0.5 sec. and 1.0 sec. after the onset
      of grip were good (ICC=.77 to .93). The time of reaching an inflection force
      value appeared at 0.3 sec. after the onset of grip, corresponding to 80% of
      maximal grip force, and the reliabilities of the parameters regarding inflection
      point were good (ICC=.77 to .95). The time determined by boundary data between
      the former and the latter regression data set and the regression coefficient
      during the developmental phase correlated significantly with the time of reaching
      90% of maximal grip force, the integrated area, and the quotient values of the
      integrated areas up to 0.25, 0.5, and 1.0 sec. divided by maximal grip force (rs=
      .78 to -.96 and -.75 to 0.88, respectively, p<.05). However, these parameters did
      not correlate with maximal grip force. A force during the developmental phase and
      maximal grip force can depend on different physiological factors. The time
      determined by boundary data between the former and the latter regression data set
      and the regression coefficient during the developmental phase are useful
      parameters for evaluating static explosive grip.

PMID- 15141916
TI  - Sport injuries: relations to sex, sport, injured body region.
AB  - The present study evaluated the association among sex, sport, and injured body
      region of sport injuries. The subjects were 329 men and 127 women, ranging in age
      from 17 to 28 years, attending classes in the departments of Physical Training
      and Sport of Ataturk University (Erzurum, Erzincan, and Agri in Turkey). There
      were no differences between men and women in percentages of injuries. The
      difference among various sports in the percentages of injured athletes was
      statistically significant. Running had the lowest percentage of injuries and
      basketball had the highest percentage. The most frequently injured body regions
      were the foot and the ankle in basketball, volleyball, soccer, and running, but
      in wrestling, the knee. These findings suggest that injury rates are associated
      with the sport rather than sex of player, and the most frequently injured body
      regions are the lower extremities. Therefore, the muscles of lower extremity
      should be strengthened to avoid injuries.

PMID- 15141917
TI  - Comparison of two training methods to enhance awareness of the oral cavity.
AB  - This investigation assessed two training methods to heighten awareness of the
      oral cavity in normal adult speakers of English. A pretest-posttest design was
      used. 40 subjects (M age=25.6 yr., SD=8.7) who passed a speech and hearing
      screening were placed into two equal-sized groups. Each group received 10 hr. of
      training over 3 wk. The Experimental group received verbal instructions regarding
      how the phonemes of English are produced, including tongue height, location, and
      contact with other structures in the oral cavity. Subjects in the Experimental
      group also used a tongue blade to enhance lingual awareness. The Control group
      received instructions in articulatory placement only. The Lingual Awareness Test
      required subjects to imitate 7 English syllables and answer 4 multiple-choice
      questions regarding lingual contact for each syllable. Posttest scores for the
      Experimental group were significantly better for one phoneme. The Control group
      made no significant improvement.

PMID- 15141918
TI  - Development of the sport achievement orientation questionnaire for Japanese
      athletes by exploratory factor analysis.
AB  - In this study, a questionnaire to assess achievement orientation in sport for
      Japanese athletes was developed. We created the questionnaire by picking items
      from free descriptions of Japanese athletes and using factor analysis of the
      responses in a Japanese sport setting. The subjects were 2,415 athletes (M=16.7
      yr., SD=2.7) in Japan. Factor analyses in this study identified three factors.
      Top Level Orientation, Demonstrating Ability Orientation, and Win Orientation,
      respectively. An examination of the intercorrelations among the three scores
      showed the subscales were related. There were no correlations between the new
      measure and the Japanese versions of the Sport Orientation Questionnaire and the
      Task and Ego Orientation in Sport Questionnaire except that the correlation of
      Win Orientation and the SOQ Athletic Success Orientation was low and negative.
      These results suggested that the three subscales appeared to be separate but
      related factors, and that it is an original measurement for only Japanese
      athletes. The overall factor reliability and validity based on the sample
      suggested that the Sport Achievement Orientation Questionnaire for Japanese
      Athletes can be valuable means for the investigation of achievement orientation
      in Japanese sport and exercise settings.

PMID- 15141919
TI  - Human pulling strengths in different conditions of exertion.
AB  - This study tested 29 young Taiwanese men and 31 young Taiwanese women to examine
      the effects of pulling type (one-handed and two-handed) and height (48 cm, 84 cm,
      120 cm, and 156 cm) on maximum horizontal isometric pulling strengths. Analysis
      showed differences in pulling strength between one-handed and two-handed efforts
      were surprisingly small for free pulling postures. The pulling strength decreased
      significantly with pulling height. The highest pulling strength was approximately
      two to three fold the lowest pulling strength across the four pulling heights.
      The women's pulling strength was approximately 59% to 67% of men's pulling
      strength. The test-retest correlations for pulling strength were satisfactory.
      The correlations between pulling strength and subjects' anthropometry were not
      sufficiently high to justify the prediction of strength. Most correlations
      between strengths in any two different pulling conditions were high and
      significant.

PMID- 15141920
TI  - Concurrent validity of tests to measure the coordinated exertion of force by
      computerized target pursuit.
AB  - The purpose of this study was to examine concurrent validity of a new test for
      coordinated exertion of force. Coordinated exertion of force was measured using
      computerized target pursuit from the following viewpoints: the relations between
      the new test, a pursuit-rotor test, and a pegboard test. College students (24 men
      and 24 women) were required to change their grip exertion to match changing
      demand values (displayed in either a bar chart or a wave form) appearing on the
      display of a personal computer. The sum of the differences between the demanded
      values and grip-exertion values for 25 sec. was a parameter to evaluate the new
      test. The reliabilities of the new test, the pursuit-rotor, and the pegboard test
      were acceptable (ICC = .70 to .99). Scores on the new test showed low
      correlations with the pursuit-rotor and the pegboard test. The relation between
      the two different displays in the new test was significant but low (r = .49, p <
      .05). It was inferred that the new test measures a somewhat different ability
      than that measured by the pursuit-rotor and pegboard test and that the abilities
      tested by the types of displayed demand values are somewhat different.

PMID- 15141921
TI  - Effects of reducing attentional demands on performance of reading comprehension
      tests by third graders.
AB  - The researchers examined the effects of reducing attentional demands on reading
      comprehension test scores. Third grade students (N=939) completed two forms (T &
      S) of the Stanford 9 Reading Comprehension Test (54 items, 50 min.) in the spring
      of 1999. Form T (state-mandated) was administered following standardized
      procedures in one session. Form S (alternate) was administered in multiple,
      divided-time sessions, that is, the total test time and items were divided in
      halves and thirds per session to lessen attentional demands. A repeated-measure
      analysis of variance yielded significant effects for average and low readers. A
      resource match explanation and a metacognitive explanation are offered for the
      results, and educational implications are discussed.

PMID- 15141922
TI  - Field dependence-independence in complex motor skills.
AB  - This study analyzed the relationship between field dependence-independence and
      complex motor skills. According to the requirements of each sporting activity,
      subjects' motor system can be mainly controlled through exteroceptive or
      proprioceptive information. Sport performances require the athlete to disembed
      himself, other players, or the ball from the background, and decision-making
      appears to require cognitive restructuring. 26 athletes (13 men and 13 women)
      involved in acrobatic sports (gymnastics, trampoline, half-pipe snowboard,
      synchronized 3-m springboard, acrobatic rock, skateboard, and free skating) and
      26 athletes (13 men and 13 women) involved in individual racket sports (tennis
      and table-tennis) completed the Group Embedded Figures Test. Participants (at
      least 10 years of practice) were from 16 to 35 years of age (M=22.0, SD=3.1). No
      significant difference among athletes on scores for field dependence-independence
      was evidenced given this expertise, sex, or age. Significantly higher scores were
      obtained by athletes in acrobatic sports, indicating that they tended to be
      predominately more field-independent whereas the lower scores were obtained by
      tennis and table-tennis players.

PMID- 15141923
TI  - Validity of specific motor skills in predicting table-tennis performance in
      novice players.
AB  - An experiment assessed whether novice table-tennis players' ball-balancing and
      bouncing skills could predict their performances after a semester of being
      coached. A pretest-posttest design was used to test this hypothesis with 82 male
      and 77 female physical education students who initially performed the skills and
      subsequently participated in a round-robin tournament. Moderate negative but
      significant (p<.01) Spearman rank-order correlation coefficients were obtained
      between some of the ball control skills scores and overall ranking in the table
      tennis tournament.

PMID- 15141924
TI  - A cognitive-behavioral intervention program for students with special reading
      disabilities.
AB  - Interaction among cognitive, meta-cognitive, and emotional factors seems to play
      a determining part in achievement behavior and especially in scholastic
      performance. In this study some preliminary results are presented of the
      implementation of a multidimensional cognitive-behavioral psychoeducational
      program especially designed for students with reading disabilities in which
      parents and teachers also take part. The aim of the program was to provide
      students with appropriate emotional and cognitive skills with which to address
      their learning problems. First results on the efficacy of the implemented program
      to 20 primary school boys and girls with special reading disabilities encourage
      research on management of learning problems with focus on cognitive and emotional
      aspects in which parents and teachers contribute. Research including a control
      group is necessary.

PMID- 15141925
TI  - Gun availability and use of guns for suicide, homicide, and murder in Canada.
AB  - A reliability check of Lester's (2000b) 1970-1995 time series that examined
      associations between the availability of firearms and their use for homicide and
      suicide in Canada. For the period 1974 to 1999, the relative availability of
      firearms as measured by the rate of accidental death from firearms and the
      average of the percentages of suicides + homicides using firearms was positively
      associated with the rate of homicide by firearms but not negatively associated
      with the rate of homicide by all other methods, and positively associated with
      the rate of suicide by firearms and negatively associated with the rate of
      suicide by all other methods. Correlations for the homicide versus murder rates,
      homicide rate using guns versus murder rate using guns, and homicide rate by all
      other methods versus murder rate by all other methods were very similar. There
      was a decrease over time of total suicide and homicide rates and firearm suicide
      and homicide rates, and with a slight indication of substitution of other methods
      for suicide.

PMID- 15141926
TI  - Stimulus array onset as a preparatory signal in attentional selection.
AB  - Warning signals enhance psychomotor performance by optimising preparation for the
      arrival of an event. Recent evidence, however, suggests that a warning signal can
      also disrupt attentional preparation by interfering with the process of
      preparing. It was hypothesised that a warning signal consisting of a change to
      the task-relevant items (array onset) may be more effective than a traditional
      warning signal consisting of the arrival, or removal, of a bar-cue which is
      independent of the task array. In three experiments array onset was a more
      effective warning signal than the bar-cue because reaction times were
      significantly faster without an increase in errors. In addition, an auditory
      warning signal resulted in faster reaction time than the bar-cue but in
      performance equivalent to that with an onset warning signal. Thus, the
      superiority of an auditory warning signal, reported by Davis and Green, was not
      found, when the interference of the visual warning signal with preparation was
      reduced. These results suggest that a visual warning signal consisting of a
      change to the stimulus array is more effective than an event independent from the
      stimulus array.

PMID- 15141927
TI  - Measuring perceptual speed in complex everyday situations.
AB  - This paper describes first results of the development of a new test to measure
      perceptual speed in everyday situations. The new items are best described as
      images depicting typical situations in everyday life, which have some picture
      elements in common. The pictures were presented to the subjects for a short time,
      and their task was to indicate which of 5 goal stimuli were present in the
      respective pictures seen before. In two studies, the scalability of the new items
      according to the Rasch model was investigated. In Study 1 data from 316 subjects
      with heterogeneous educational backgrounds were used in the empirical analysis.
      The results of Study 1 indicate that Rasch homogeneity and thus positive
      psychometric properties for the new test could be obtained. This result was
      further validated using a second sample (N = 198). The validation study
      replicates the results obtained in Study 1. These results represent a substantial
      condition sine qua non for following studies on the construct and criterion
      validity of the new test.

PMID- 15141928
TI  - Perceived exertion during resistance exercise by children.
AB  - This pilot study examined the validity of a new scale of perceived exertion
      during acute bouts of resistance exercise in young children. The researchers
      developed an 11-point numerical scale with five pictures representing youths at
      various levels of exertion while lifting weights. 26 children (M age 10.1 +/- 1.2
      yr.) performed one set of 10 repetitions at 35%, 55%, and 75% of their one
      repetition maximum on the chest press and leg press exercises using child-size
      weight training machines. Scaling procedures for the perceptual anchors on the
      perceived exertion scale were based on one repetition maximum testing. Children
      could use this scale to translate into numbers their perceptions of physical
      exertion during upper and lower body resistance exercise. Perceived exertion
      distributed as a positive linear function of the percent of one repetition
      maximum on the chest press and leg press exercises (rs = .70 to .77), and
      perceived exertion increased significantly across all three exercise intensities
      on both exercises. These preliminary findings provide partial evidence for
      validation when this scale was used during resistance exercise with children.
      Additional validation regarding perceived exertion during resistance exercise
      with children is warranted.

PMID- 15141929
TI  - Study time effects in recognition memory.
AB  - We empirically tested the assumption that study time increases recognition
      accuracy because the storage of information is better when study time is longer
      as Shiffrin and colleagues have reported, an assumption common to parallel models
      of recognition. In the present study with 123 subjects, we examined the effect of
      item strength on four measures: hit rate, false alarm rate, d', and beta, for a
      single-word recognition task with longer study times than those usually used in
      the literature. Analysis indicated significant increase for hit rate and d' and a
      decrease in false alarm rate, as one goes from weak to stronger study conditions,
      and a change in ln(beta) when study time is greater than 1 sec. These results
      suggest that familiarization is one, but not the only, factor underlying the
      strength-mirror effect.

PMID- 15141930
TI  - Effects of expectations about evaluation and peer recommendations on students'
      ratings.
AB  - Previous research on consumer satisfaction suggests that the anticipation of
      providing a later evaluation leads to more negative appraisals. Within the
      context of higher education, the current experiment focused on the evaluation of
      a presentation and its presenter. College students (35 men, 59 women) were
      randomly assigned to six conditions regarding evaluative expectations and peer
      recommendations. Students watched a brief video of a lecture on an educational
      topic and then evaluated the speaker and presentation. Anticipation of providing
      evaluations did not influence the subsequent evaluations; however, peers'
      positive recommendations led to more positive evaluations whereas negative
      recommendations led to more negative evaluations.

PMID- 15141931
TI  - Cortical and subcortical dynamics of aging with HIV infection.
AB  - Given pharmaceutical advancements, more people with HIV will be living to old
      age. Cognitive declines have been observed both during normal aging and in people
      with HIV; whether there are cumulative cognitive declines in adults aging with
      HIV remains unknown. Based on current literature, adults aging with HIV may be at
      risk for psychomotor declines that resemble parkinsonianism.

PMID- 15141932
TI  - A study of 60- to 89-mo.-old children's skill at writing numerals.
AB  - The skill of writing numerals necessitates a certain developmental maturity.
      Studying the age at which children start to develop this skill and assessing
      problems they encounter while writing numerals should give direction to their
      training. From 8 schools a total of 267 children, ages 60 to 89 mo., were asked
      to write the numerals 1 to 9. Analysis showed that 80% of the children wrote most
      of the numerals correctly, 15% wrote inverted numerals, 2.0% wrote some numerals
      as letters, and 4% did not write certain numerals at all. In addition, 64% of
      children ages 60 to 65 mo. gave correct responses, and the perception of correct
      responses increased across age groups until 95% were correct in the group who
      were 84 to 89 mo. There was no significant difference between girls and boys in
      these writing skills.

PMID- 15141933
TI  - Neuropsychological executive functions of adolescent sex offenders and nonsex
      offenders.
AB  - A growing body of research now suggests that a substantial number of criminal
      offenders display neuropsychological deficits, especially frontal-executive
      dysfunctions. The present study investigated the possibility of similar deficits
      by comparing the performance of 60 adolescent sex offenders court-ordered to a
      residential treatment facility with the performance of 60 nonsexual delinquent
      offenders matched on several pertinent sociodemographic characteristics and
      scores on four neuropsychological tests: (1) the Trail Making Test, (2) the
      Controlled Oral Word Association test of the Multilingual Aphasia Examination,
      (3) the Tower of London, and (4) the Wisconsin Card-sorting Test. Analysis
      indicated a pattern of frontal-executive dysfunction in a subset of both groups
      of offenders; this pattern has both theoretical and treatment implications.

PMID- 15141934
TI  - On the independence of golf scores for professional golfers.
AB  - This study involved professional golfers who played in 1999 on the Professional
      Golfers' Association Tour (PGA Tour, N=2,967), Senior Professional Golfers'
      Association (SPGA Tour, N=2,751), and the Ladies Professional Golfers'
      Association (LPGA Tour, N=2,638) and investigated whether there is independence
      between golfers' scores on consecutive rounds within tournaments. The mean
      correlations between scores on consecutive rounds for players on the PGA Tour (r=
      .08, p<.01) and LPGA Tour (r=-.03, p=.05) were negative although negligible and
      of little practical importance. There was a small, positive correlation (r=.27,
      p<.01) between scores on consecutive rounds for players on the SPGA Tour. Such
      evidence suggests the greater dependence of golf scores on the SPGA Tour may be
      due to the greater range of players' skill on that tour.

PMID- 15141935
TI  - Contrast influences perceived duration of brief time intervals.
AB  - 34 participants judged the duration of a 4-sec. interval which was preceded by a
      contextual interval of 2, 6, 10, or 14 sec. Underestimations of the test interval
      when the contextual intervals were longer suggested temporal durations are
      affected by a mechanism of comparing and contrasting analogous to the one
      producing some visual illusions.

PMID- 15141936
TI  - Psychometric properties of the Spanish version of the self-perception profile for
      children.
AB  - Harter's Self-perception Profile for Children was designed to assess children's
      domain-specific judgments of their competence (scholastic, social, athletic,
      physical, and behavioral), as well as global self-worth. The psychometric
      properties and exploratory factor analysis of the profile for two Spanish samples
      of children (49% boys and 51% girls; M age=11.1 yr., SD=9.7), were examined (n=23
      from an after-school social care center in an economically deprived neighborhood
      and n=120 from a private school mainly enrolling families of medium socioeconomic
      status). All attending children between 9 and 12 yr. old were included. Analysis
      showed sex differences, with girls scoring lower than boys on Athletic Competence
      and higher on Behavioral Conduct. Children from the economically deprived group
      had higher scores on Social Acceptance and lower scores on Physical Appearance.
      The cross-cultural analysis showed that the Spanish control group scored
      significantly higher than the original American control group on Global Self
      worth. A Spanish validation with 9- to 12-yr.-olds clearly replicated the five
      factor structure reported by Harter in 1985 and also replicated the results
      obtained in other European samples, showing reliable and valid psychometric
      properties.

PMID- 15141937
TI  - Children's perceptions of dangerous substances.
AB  - The aim of this research was to examine age differences in children's perceptions
      of dangerous substances. Children's responses to photographs of child models
      encountering alcohol, a syringe, medicine, glue, and household bleach were coded
      for recognition of substance, awareness of potential danger, and understanding of
      danger or harm. Responses from 59 children (28 girls and 31 boys, who were all
      children of the required age in an urban primary school) were compared across
      three age groups (6-7 years, 8-9 years, and 10-11 years). 15 to 18 of 20 children
      in each of three age groups recognised all the dangerous substances. Significant
      differences across age groups were found for awareness of the potential harm from
      alcohol, glue, and medicine, but not for the syringe or bleach. Children reported
      less serious consequences from ingesting alcohol than other substances, the
      consequences of sniffing glue tended to be confused with the sticking properties
      of glue, children's understanding of transmission of germs, disease, and AIDS
      through syringes was varied, and there was a tendency among the older children to
      underestimate the potential harm of self-administration of medicines. Findings
      were discussed in relation to children's concepts of danger and safety education.

PMID- 15141938
TI  - Personal and social bases of children's self-concepts about physical movement.
AB  - This project examined the personal and social bases of children's self-concepts
      about physical movement. Children completed the Movement Assessment Battery, ASK
      KIDS self-concept inventory, personal and social self-categorizations.
      Participants were girls and boys from 5 to 12 years old. Study 1 (N=242)
      confirmed that the ASK-KIDS self-concept inventory could be extended to physical
      movement for younger and older girls and boys. In Study 2 (N=42), self-concepts
      about movement were not necessarily associated with actual performance and
      personal self-categorizations about oneself as a 'bookish' or 'sporty' person. In
      contrast, self-concepts about physical movement were associated with social self
      categorizations regarding age and sex. Study 3 (N=70) confirmed the social basis
      of children's self-concepts about movement. Self-concepts about physical movement
      were associated with children's sense of belonging and not with a sense of
      individuality. The findings have implications for the design of programs that
      motivate children to participate in physical activities.

PMID- 15141939
TI  - Validity and reliability of a Cantonese-translated rating of perceived exertion
      scale among Hong Kong adults.
AB  - This study assessed the validity and reliability of the Cantonese-translated
      version of the Borg 6-20 Rating of Perceived Exertion (RPE) scale during
      continuous incremental cycle ergometry by Hong Kong adults. A total of 54
      participants (25 males and 29 females), ages 22.2 +/- 4.7 yr., volunteered to
      participate. They performed two trials of identical continuous incremental
      cycling exercise 1 wk. apart for the reliability test. The objective measures of
      exercise intensity (heart rate, power output, and oxygen consumption) and the
      subjective measure of effort (RPE) were obtained during the incremental exercise.
      Significant (p < .01) Pearson correlations were found when RPE values were
      correlated with heart rate (rs > or = .73), power output (rs > or = .69), and
      oxygen consumption (rs > or = .68). The overall test-retest intraclass
      correlation (R = .92) indicated that the scale was reliable. In conclusion, this
      Cantonese scale for rating of perceived exertion appears to be a valid and
      reliable psychophysiological tool to measure perceptions of exertion during
      controlled cycle ergometer exercise by Hong Kong adults.

PMID- 15141940
TI  - Review of some sex-related effects of forced unilateral nostril breathing on the
      autonomic nervous system.
AB  - Sex-related effects of forced unilateral nostril breathing on the autonomic
      nervous system are considered. Recent studies described the effects of such
      breathing on autonomic activity as sex-specific as in prior studies.

PMID- 15141941
TI  - The complete mitochondrial genome sequence of the haptophyte Emiliania huxleyi
      and its relation to heterokonts.
AB  - The complete nucleotide sequence of the mitochondrial genome of Emiliania huxleyi
      (Haptophyta) was determined. E. huxleyi is the most abundant coccolithophorid,
      key in many marine ecosystems, and plays a vital role in the global carbon cycle.
      The mitochondrial genome contains genes encoding three subunits of cytochrome c
      oxidase, apocytochrome b, seven subunits of the NADH dehydrogenase complex, two
      ATPase subunits, two ribosomal RNAs, 25 tRNAs and five ribosomal proteins. One
      potentially functional open reading frame was identified, with no counterpart in
      any other organism so far studied. The cox1 gene transcript is apparently spliced
      from two distant segments in the genome. One of the most interesting features in
      this mtDNA is the presence of the dam gene, which codes for a DNA adenine
      methyltransferase. This enzyme is common in bacterial genomes, but is not present
      in any studied mitochondrial genome. Despite the great age of this group (ca. 300
      Ma), little is known about the evolution of haptophytes or their relationship to
      other eukaryotes. This is the first published haptophyte organellar genome, and
      will improve the understanding of their biology and evolution and allow us to
      test the monophyly of the chromoalveolate clade.

PMID- 15141942
TI  - Distinctive features of plant organs characterized by global analysis of gene
      expression in Arabidopsis.
AB  - The distinctive features of plant organs are primarily determined by organ
      specific gene expression. We analyzed the expression specificity of 8809 genes in
      7 organs of Arabidopsis using a cDNA macroarray system. Using relative expression
      (RE) values between organs, many known and unknown genes specifically expressed
      in each organ were identified. We also analyzed the organ specificity of various
      gene groups using the GRE (group relative expression) value, the average of the
      REs of all genes in a group. Consequently, we found that many gene groups even
      ribosomal protein genes, have strong organ-specific expression. Clustering of the
      expression profiles revealed that the 8809 genes were classified into 9 major
      categories. Although 3451 genes were clustered into the largest category, which
      showed constitutive gene expression, 266 and 1005 genes were found to be root-
      and silique-specific genes, respectively. By this clustering, particular gene
      groups which showed multi-organ-specific expression profiles, such as bud-flower
      specific, stem-silique-specific or bud-flower-root-specific profiles, could be
      effectively identified. From these results, major features of plant organs could
      be characterized by their distinct profiles of global gene expression. These data
      of organ-specific gene expression are available at our web site: Arabidopsis
      thaliana Tissue-Specific Expression Database, ATTED
      (http://www.atted.bio.titech.ac.jp/).

PMID- 15141943
TI  - The genome sequence of silkworm, Bombyx mori.
AB  - We performed threefold shotgun sequencing of the silkworm (Bombyx mori) genome to
      obtain a draft sequence and establish a basic resource for comprehensive genome
      analysis. By using the newly developed RAMEN assembler, the sequence data derived
      from whole-genome shotgun (WGS) sequencing were assembled into 49,345 scaffolds
      that span a total length of 514 Mb including gaps and 387 Mb without gaps.
      Because the genome size of the silkworm is estimated to be 530 Mb, almost 97% of
      the genome has been organized in scaffolds, of which 75% has been sequenced. By
      carrying out a BLAST search for 50 characteristic Bombyx genes and 11,202 non
      redundant expressed sequence tags (ESTs) in a Bombyx EST database against the WGS
      sequence data, we evaluated the validity of the sequence for elucidating the
      majority of silkworm genes. Analysis of the WGS data revealed that the silkworm
      genome contains many repetitive sequences with an average length of <500 bp.
      These repetitive sequences appear to have been derived from truncated
      transposons, which are interspersed at 2.5- to 3-kb intervals throughout the
      genome. This pattern suggests that silkworm may have an active mechanism that
      promotes removal of transposons from the genome. We also found evidence for
      insertions of mitochondrial DNA fragments at 9 sites. A search for Bombyx
      orthologs to Drosophila genes controlling sex determination in the WGS data
      revealed 11 Bombyx genes and suggested that the sex-determining systems differ
      profoundly between the two species.

PMID- 15141944
TI  - Coordinate downregulation of a novel imprinted transcript ITUP1 with PEG3 in
      glioma cell lines.
AB  - The human paternally expressed gene 3 (PEG3) on chromosome 19q13.4 is one of the
      candidate tumor suppressor genes for glioma. We have previously reported that the
      epigenetic silencing of PEG3 expression in glioma cell lines is dependent on
      aberrant DNA methylation of an exonic CpG island. Here, we have identified three
      expressed sequence tags (ESTs), H80201, H78825 and AW197312, that exhibit
      paternal allele-specific expression, using human monochromosomal hybrids
      containing the paternal or maternal origin of PEG3 locus. The EST H80201 was
      shown to be expressed only from the paternal allele in normal human lymphoblasts
      by utilizing a single nucleotide polymorphism (SNP). Monoallelic expression of
      EST H80201 was also detected in non-tumor adult human brain tissues of gliomas.
      These ESTs were located directly adjacent to PEG3 in a head-to-head orientation.
      We have named this new transcript, imprinted transcript 1, which is located
      upstream but oppositely oriented to PEG3 (ITUP1). The ITUP1 showed a similar
      expression profile with PEG3 in glioma cell lines. Bisulfite genomic sequencing
      and reverse transcription (RT)-PCR analysis indicated that hypermethylation of
      the promoter region correlated with the absence of these transcripts. This
      suggests that ITUP1 and PEG3 are coordinately regulated, and that downregulation
      of the both genes may be important in the development of glioma.

PMID- 15141945
TI  - Nucleotide substitutions in Staphylococcus aureus strains, Mu50, Mu3, and N315.
AB  - A specific phenotype of Staphylococcus aureus strains Mu50 and Mu3 is
      characterized by thickened cell wall and moderate resistance to vancomycin. The
      N315 strain is a prototype of methicillin-resistant S. aureus (MRSA), but it is
      methicillin susceptible, despite carrying the mecA resistance gene. Here, we
      revised differences in the sequences of Mu50 and N315, referencing that of Mu3
      which were assumed to be of one lineage. The 362 ORFs diverse between Mu50 and
      N315 were picked up, and the corresponding ones in three strains were re
      sequenced. This defined 213 ORFs diverse between Mu50 and N315, and 9 between
      Mu50 and Mu3. The fixed diversities of 174 ORFs (except for 39 silent ORFs from
      213), including nucleotide substitution (NSs), frame shift, and truncation were
      grouped into three major functional categories, which were transport (14.9% in
      the 174 diverse ORFs), metabolism of carbohydrates (5.7%), and RNA synthesis
      (9.6%). The other gene categories had small diversities. These gene categories
      seemed to be functionally decisive for the Mu50-specific characters, the
      thickened cell wall and moderate vancomycin resistance. All of the diverse genes
      and the high quality sequence of Mu50 can be viewed at the web site
      (http://133.5.48.239/VRSA/).

PMID- 15141946
TI  - Genome-wide comparison of the His-to-Asp phosphorelay signaling components of
      three symbiotic genera of Rhizobia.
AB  - Histidine-to-aspartate (His-Asp) phosphorelay (or two-component) systems are very
      common signal transduction mechanisms that are implicated in a wide variety of
      cellular responses to environmental stimuli. The His-Asp phosphorelay components
      include "sensor histidine kinase (HK)", "phosphotransfer intermediate (HPt)", and
      "response regulator (RR)". With special reference to three bacterial species
      (Mesorhizobium loti, Bradyrhizobium japonicum, Sinorhizobium meliloti), each of
      which belongs to a different genera of Rhizobia, here we attempted to compile all
      of the His-Asp phosphorelay components in order to reveal a comparative genome
      wide overview as to the His-Asp phosphorelay. It was revealed that M. loti has 47
      HKs, 1 HPts, and 58 RRs; B. japonicum has 80 HKs, 3 HPts, and 91 RRs; whereas S.
      meliloti has 40 HKs, 1 HPt, and 58 RRs. These His-Asp phosphorelay components
      were extensively compiled and characterized. The resulting overview as to the His
      Asp phosphorelay of Rhizobia will provide us with a basis for understanding of
      the fundamental mechanisms underlying interactions between plants and
      microorganisms (including symbiosis), as well as nitrogen fixation.

PMID- 15141947
TI  - The complete mitochondrial genome sequence of the haptophyte Emiliania huxleyi
      and its relation to heterokonts (supplement).

PMID- 15141948
TI  - The HopPtoF locus of Pseudomonas syringae pv. tomato DC3000 encodes a type III
      chaperone and a cognate effector.
AB  - Type III secretion systems are highly conserved among gram-negative plant and
      animal pathogenic bacteria. Through the type III secretion system, bacteria
      inject a number of virulence proteins into the host cells. Analysis of the whole
      genome sequence of Pseudomonas syringae pv. tomato DC3000 strain identified a
      locus, named HopPtoF, that is homologous to the avirulence gene locus avrPphF in
      P. syringae pv. phaseolicola. The HopPtoF locus harbors two genes, ShcF(Pto) and
      HopF(Pto), that are preceded by a single hrp box promoter. We present evidence
      here to show that ShcF(Pto) and HopF(Pto) encode a type III chaperone and a
      cognate effector, respectively. ShcF(Pto) interacts with and stabilizes the
      HopF(Pto) protein in the bacterial cell. Translation of HopF(Pto) starts at a
      rare initiation codon ATA that limits the synthesis of the HopF(Pto) protein to a
      low level in bacterial cells.

PMID- 15141950
TI  - Characterization of the multiple-copy host-selective toxin gene, ToxB, in
      pathogenic and nonpathogenic isolates of Pyrenophora tritici-repentis.
AB  - ToxB, a gene that encodes a 6.6-kDa host-selective toxin (HST), is present in
      several races of the wheat pathogen Pyrenophora tritici-repentis. To learn more
      about the multiple ToxB open reading frames (ORFs), six of the estimated nine
      copies from a race 5 isolate were cloned and analyzed. All six copies of ToxB
      have identical 261-bp ORFs and thus encode the same form of Ptr ToxB. Sequence
      analysis of regions flanking the cloned ToxB loci revealed that the majority of
      loci are associated with portions of retrotransposons and a transposon-like
      sequence. Data indicate that ToxB loci reside on two chromosomes, 3.5 and 2.7 Mb,
      with the majority of copies located on the 2.7 Mb chromosome. A related gene,
      referred to as toxb, from a nonpathogenic race 4 isolate was also cloned and
      characterized. This is interesting because, until now, HST genes have only been
      found in toxin-producing, pathogenic isolates of plant pathogenic fungi. The toxb
      gene from nonpathogenic isolates is 86% similar to ToxB, and data suggest that
      toxb is a single-copy gene. No toxb transcript was detected under culture
      conditions that favor the expression of ToxB; therefore, these genes differ in
      their transcriptional regulation.

PMID- 15141949
TI  - The disruption of a Galpha subunit sheds new light on the pathogenicity of
      Stagonospora nodorum on wheat.
AB  - Gna1, a gene encoding a Galpha subunit, a key component of signal transduction
      pathways, has been cloned and characterized in the wheat pathogen Stagonospora
      nodorum. Analysis of Gna1 expression during infection revealed a slight decrease
      in transcript levels shortly after germination, after which levels steadily
      increased until sporulation. Inactivation of Gna1 had a pleiotropic effect on
      phenotype. The Gna1 mutants were less pathogenic, attributed to coinciding with a
      defect in direct penetration. Also, Gna1 mutants were unable to sporulate, showed
      an albino phenotype, and secreted one or more brown pigments into growth media.
      Analysis of growth medium identified tyrosine, phenylalanine, and
      dihydroxyphenylalanine (L-DOPA) were excreted by the Gna1 strains but not by wild
      type. The presence of these compounds, and the insensitivity of melanization to
      tricyclazole suggest that S. nodorum synthesizes melanin via the L-DOPA pathway,
      the first fungal phytopathogen described to do so. Decreases in protease (and
      several other depolymerases) activities and sensitivity to osmotic stress were
      other phenotypes identified in the Gna1 mutants. Gna1 is the first signal
      transduction gene to be cloned and characterized from S. nodorum and its
      inactivation has uncovered several previously unknown facets of pathogenicity.

PMID- 15141951
TI  - The avirulence domain of Cauliflower mosaic virus transactivator/viroplasmin is a
      determinant of viral virulence in susceptible hosts.
AB  - Cauliflower mosaic virus (CaMV) transactivator/viroplasmin (Tav) is a
      multifunctional protein essential for basic replication of CaMV. It also plays a
      role in viral pathogenesis in crucifer and solanaceous host plants. Deletion
      mutagenesis revealed that N- and C-terminal parts of Tav are not essential for
      CaMV replication in transfected protoplasts. Two deletion mutants having only
      minimal defects in basic replication were infectious in turnips but only with
      highly attenuated virulence. This was shown to be due to delayed virus spread
      within the inoculated leaves and to the upper leaves. Unlike the wild-type virus,
      the mutant viruses successfully spread locally without inducing a host defense
      response in inoculated Datura stramonium leaves, but did not spread systemically.
      These results provide the first evidence that a Tav domain required for
      avirulence function in solanaceous plants is not essential for CaMV infectivity
      but has a role in viral virulence in susceptible hosts.

PMID- 15141953
TI  - Ptr ToxA requires multiple motifs for complete activity.
AB  - Ptr ToxA was the first proteinaceous necrosis-inducing toxin identified and
      cloned from the wheat pathogen, Pyrenophora tritici-repentis. How this protein
      causes necrosis in sensitive wheat cultivars is not known. In an effort to
      understand the structural features of Ptr ToxA required for induction of
      necrosis, we employed a combination of site-directed mutagenesis and peptide
      inhibition studies. Mutagenesis was carried out on conserved motifs within the
      active domain of Ptr ToxA. Proteins with mutations of potential casein kinase 2
      phosphorylation sites but not protein kinase C phosphorylation sites have
      significantly reduced activity. Additionally, mutations in a region with high
      homology to amino acids surrounding and including the RGD cell attachment motif
      of vitronectin result in proteins with significantly less activity than Ptr ToxA.
      The importance of the vitronectin-like motif was confirmed by a decrease of Ptr
      ToxA-induced activity when coinfiltrated with peptides corresponding to amino
      acids within this motif. Reduction in Ptr ToxA activity by competition with
      mutant proteins demonstrates the necessity of multiple motifs for Ptr ToxA
      activity.

PMID- 15141952
TI  - The barley apoptosis suppressor homologue BAX inhibitor-1 compromises nonhost
      penetration resistance of barley to the inappropriate pathogen Blumeria graminis
      f. sp. tritici.
AB  - BAX inhibitor-1 (BI-1) proteins have been characterized as suppressors of
      programmed cell death in mammals and plants. The barley BI-1 is a suppressor of
      nonspecific background resistance and mlo-mediated penetration resistance to the
      biotrophic fungal pathogen Blumeria graminis f. sp. hordei when overexpressed in
      epidermal cells of barley. We report here that BI-1 expression is also slightly
      up-regulated during interaction with the inappropriate wheat pathogen Blumeria
      graminis f. sp. tritici. Significantly, overexpression of BI-1 in single
      epidermal cells of barley by microprojectile-mediated transformation rendered
      cells susceptible to penetration by inappropriate B. graminis f. sp. tritici. The
      degree of transgene-induced accessibility to B. graminis f. sp. tritici was
      thereby similar to the effect achieved by overexpression of the defense
      suppressor gene Mlo and could not be further enhanced by double expression of
      both BI-1 and Mlo. Confocal laser scanning microscopy was used to locate a
      functional green fluorescing GFP:BI-1 fusion protein in endomembranes and the
      nuclear envelope of barley epidermal cells. Together, enhanced expression of
      barley BI-1 suppresses penetration resistance to B. graminis f. sp. tritici,
      linking barley nonhost resistance with cell death regulation.

PMID- 15141954
TI  - Potyviral 6K2 protein long-distance movement and symptom-induction functions are
      independent and host-specific.
AB  - Deletion of various portions, or insertion of six histidine residues (6xHis) into
      various positions of the membrane-bound 6K2 protein (53 amino acids) of Potato
      virus A (PVA, genus Potyvirus), inhibited systemic infection in Nicotiana tabacum
      and N. benthamiana plants. However, a spontaneous mutation (Gly2Cys) that
      occurred in 6K2 adjacent to the 6xHis insert placed between Ser1 and Gly2 enabled
      systemic infection in a single N. benthamiana plant. No symptoms were observed,
      but virus titers were similar to the symptom-inducing wild-type (wt) PVA. N.
      tabacum plants were not systemically infected, albeit virus propagation was
      observed in inoculated protoplasts. The 6xHis/Gly2Cys mutant was reconstructed in
      vitro and serially propagated by mechanical inoculation in N. benthamiana.
      Following the third passage, a novel viral mutant appeared, lacking the last four
      His residues of the insert, as well as the Gly2 and Thr3 of 6K2. It infected N.
      tabacum plants systemically, and in the systemically infected N. benthamiana
      leaves, vein chlorosis and mild yellowing symptoms were observed, typical of wt
      PVA infection. The mutant virus accumulated to titers similar to wt PVA in both
      hosts. These results show that the PVA 6K2 protein affects viral long-distance
      movement and symptom induction independently and in a host-specific manner.

PMID- 15141955
TI  - Arabidopsis DND2, a second cyclic nucleotide-gated ion channel gene for which
      mutation causes the "defense, no death" phenotype.
AB  - A previous mutant screen identified Arabidopsis dnd1 and dnd2 "defense, no death"
      mutants, which exhibit loss of hypersensitive response (HR) cell death without
      loss of gene-for-gene resistance. The dnd1 phenotype is caused by mutation of the
      gene encoding cyclic nucleotide-gated (CNG) ion channel AtCNGC2. This study
      characterizes dnd2 plants. Even in the presence of high titers of Pseudomonas
      syringae expressing avrRpt2, most leaf mesophyll cells in the dnd2 mutant
      exhibited no HR. These plants retained strong RPS2-, RPM1-, or RPS4-mediated
      restriction of P. syringae pathogen growth. Mutant dnd2 plants also exhibited
      enhanced broad-spectrum resistance against virulent P. syringae and
      constitutively elevated levels of salicylic acid, and pathogenesis-related (PR)
      gene expression. Unlike the wild type, dnd2 plants responding to virulent and
      avirulent P. syringae exhibited elevated expression of both salicylate-dependent
      PR-1 and jasmonate and ethylene-dependent PDF1.2. Introduction of nahG+
      (salicylate hydroxylase) into the dnd2 background, which removes salicylic acid
      and causes other defense alterations, eliminated constitutive disease resistance
      and PR gene expression but only weakly impacted the HR- phenotype. Map-based
      cloning revealed that dnd2 phenotypes are caused by mutation of a second CNG ion
      channel gene, AtCNGC4. Hence, loss of either of two functionally nonredundant CNG
      ion channels can cause dnd phenotypes. The dnd mutants provide a unique genetic
      background for dissection of defense signaling.

PMID- 15141956
TI  - Regulation of AHL production and its contribution to epiphytic fitness in
      Pseudomonas syringae.
AB  - Pseudomonas syringae forms large cell aggregates that are more stress tolerant
      than solitary cells during epiphytic growth on plants. The differential survival
      of aggregates on leaves suggests that epiphytic fitness traits may be controlled
      in a density-dependent manner via cell-cell signaling. We investigated this
      hypothesis in P. syringae B728a. Synthesis of N-acyl-homoserine lactone (AHL), 3
      oxo-hexanoyl homoserine lactone, and the expression of the gene encoding AHL
      synthase ahlI were maximal at high cell concentrations. The expression of the AHL
      regulator ahlR, in contrast, was similar at all cell concentrations. A screen of
      Tn5 mutants revealed that P. syringae B728a requires a novel transcriptional
      activator for AHL production. This regulator, which belongs to the TetR family,
      was also required for epiphytic fitness and has been designated AefR (for AHL and
      epiphytic fitness regulator). The expression of ahlI was greatly reduced in both
      aefR- and gacA- mutants and was completely restored in either mutant after
      addition of exogenous AHL. In contrast, the expression of aefR was not reduced in
      either gacS- or gacA- mutants. Thus, AefR appears to positively regulate AHL
      production independently of the regulators GacS/GacA and also controls traits in
      P. syringae B728a that are required for epiphytic colonization.

PMID- 15141957
TI  - Developmental regulation of Mi-mediated aphid resistance is independent of Mi-1.2
      transcript levels.
AB  - Mi-1.2, a member of the intracellular, nucleotide-binding site-leucine-rich
      repeat family of resistance genes, confers resistance in tomato (Lycopersicon
      esculentum) against both root-feeding nematodes and leaf-feeding aphids. Nematode
      resistance is effective in all life stages of the plant; in contrast, Mi-mediated
      aphid resistance is developmentally regulated, and protects mature plants but not
      seedlings against aphid infestation. To determine if the onset of aphid
      resistance is regulated by Mi-1.2 transcript abundance, we compared aphid
      resistance and Mi-1.2 transcript levels in seedlings and flowering plants. Paired
      bioassays and RNase protection assays revealed that Mi-1.2 is transcribed in the
      leaves prior to the onset of aphid resistance, and that transcript levels are
      comparable in seedlings and flowering life stages. Furthermore, constitutive
      overexpression of Mi-1.2 in transgenic plants did not hasten the onset of aphid
      resistance in seedlings, or boost the level of resistance observed in flowering
      plants. These data demonstrate that Mi-1.2 transcript levels do not modulate the
      degree of aphid resistance in tomato leaves, or control the differences in
      regulation between aphid and nematode resistance.

PMID- 15141958
TI  - Identification of Botrytis cinerea genes up-regulated during infection and
      controlled by the Galpha subunit BCG1 using suppression subtractive hybridization
      (SSH).
AB  - The Galpha subunit BCG1 plays an important role during the infection of host
      plants by Botrytis cinerea. Delta bcg1 mutants are able to conidiate, penetrate
      host leaves, and produce small primary lesions. However, in contrast to the wild
      type, the mutants completely stop invasion of plant tissue at this stage;
      secondary lesions have never been observed. Suppression subtractive hybridization
      (SSH) was used to identify fungal genes whose expression on the host plant is
      specifically affected in bcg1 mutants. Among the 22 differentially expressed
      genes, we found those which were predicted to encode proteases, enzymes involved
      in secondary metabolism, and others encoding cell wall-degrading enzymes. All
      these genes are highly expressed during infection in the wild type but not in the
      mutant. However, the genes are expressed in both the wild type and the mutant
      under certain conditions in vitro. Most of the BCG1-controlled genes are still
      expressed in adenylate cyclase (bac) mutants in planta, suggesting that BCG1 is
      involved in at least one additional signaling cascade in addition to the cAMP
      depending pathway. In a second SSH approach, 1,500 clones were screened for those
      that are specifically induced by the wild type during the infection of bean
      leaves. Of the 22 BCG1-controlled genes, 11 also were found in the in planta SSH
      library. Therefore, SSH technology can be successfully applied to identify target
      genes of signaling pathways and differentially expressed genes in planta.

PMID- 15141959
TI  - Two PAK kinase genes, CHM1 and MST20, have distinct functions in Magnaporthe
      grisea.
AB  - In the rice blast fungus Magnaporthe grisea, the Pmk1 mitogen-activated protein
      (MAP) kinase is essential for appressorium formation and infectious growth. PMK1
      is homologous to yeast Fus3 and Kss1 MAP kinases that are known to be regulated
      by the Ste20 PAK kinase for activating the pheromone response and filamentation
      pathways. In this study, we isolated and characterized two PAK genes, CHM1 and
      MST20, in M. grisea. Mutants disrupted in MST20 were reduced in aerial hyphae
      growth and conidiation, but normal in growth rate, appressorium formation,
      penetration, and plant infection. In chm1 deletion mutants, growth, conidiation,
      and appressorium formation were reduced significantly. Even though appressoria
      formed by chm1 mutants were defective in penetration, chm1 mutants were able to
      grow invasively on rice leaves and colonize through wounds. The chm1 mutants were
      altered in conidiogenesis and produced conidia with abnormal morphology. Hyphae
      of chm1 mutants had normal septation, but the length of hyphal compartments was
      reduced. On nutritionally poor oatmeal agar, chm1 mutants were unstable and
      produced sectors that differed from original chm1 mutants in growth rate,
      conidiation, or colony morphology. However, none of the monoconidial cultures
      derived from these spontaneous sectors were normal in appressorial penetration
      and fungal pathogenesis. These data suggest that MST20 is dispensable for plant
      infection in M. grisea, but CHM1 plays a critical role in appressorium formation
      and penetration. Both mst20 and chm1 deletion mutants were phenotypically
      different from the pmk1 mutant that is defective in appressorium formation and
      infectious hyphae growth. It is likely that MST20 and CHM1 individually play no
      critical role in activating the PMK1 MAP kinase pathway during appressorium
      formation and infectious hyphae growth. However, CHM1 appears to be essential for
      appressorial penetration and CHM1 and MST20 may have redundant functions in M.
      grisea.

PMID- 15141960
TI  - Influence of environmental conditions on the production of phenazine-1
      carboxamide by Pseudomonas chlororaphis PCL1391.
AB  - Pseudomonas chlororaphis PCL1391 produces the secondary metabolite phenazine-1
      carboxamide (PCN), which is an antifungal metabolite required for biocontrol
      activity of the strain. Identification of conditions involved in PCN production
      showed that some carbon sources and all amino acids tested promote PCN levels.
      Decreasing the pH from 7 to 6 or decreasing the growth temperature from 21 to 16
      degrees C decreased PCN production dramatically. In contrast, growth at 1% oxygen
      as well as low magnesium concentrations increased PCN levels. Salt stress, low
      concentrations of ferric iron, phosphate, sulfate, and ammonium ions reduced PCN
      levels. Fusaric acid, a secondary metabolite produced by the soilborne Fusarium
      spp. fungi, also reduced PCN levels. Different nitrogen sources greatly
      influenced PCN levels. Analysis of autoinducer levels at conditions of high and
      low PCN production demonstrated that, under all tested conditions, PCN levels
      correlate with autoinducer levels, indicating that the regulation of PCN
      production by environmental factors takes place at or before autoinducer
      production. Moreover, the results show that autoinducer production not only is
      induced by a high optical density but also can be induced by certain
      environmental conditions. We discuss our findings in relation to the success of
      biocontrol in the field.

PMID- 15141961
TI  - Biochemical effects of low level exposure to soman vapour.
AB  - The aim of this study was to demonstrate changes in acetylcholinesterase (AChE)
      and butyrylcholinesterase (BuChE) activities, tyrosine aminotransferase activity
      (TAT) and plasma corticosterone level, neuroexcitability and behavior following
      24 hours and 4 weeks of soman sublethal inhalation exposure at low level. AChE
      activity in erythrocytes and BuChE activity in plasma was decreased (dependent on
      the concentration of soman) 24 h and 4 weeks after the exposure. Similar decrease
      in AChE activity in different brain parts was observed. One of stressogenic
      parameters (TAT) was changed after 24 h exposure only. 4 weeks after the
      exposure, these parameters (corticosterone and TAT) were in the range of normal
      values. Behaviour of experimental animals was changed 24 h after the exposure
      persisting 4 weeks after the exposure as well as neuroexcitability.

PMID- 15141962
TI  - Contribution to safe anti-inflammatory therapy with indomethacin.
AB  - Non-steroidal anti-inflammatory drugs possess not only therapeutic but also
      adverse effects, mainly on the gastrointestinal tract. The aim of this pilot
      study was to establish the ulcerogenic dose caused by daily administration of
      indomethacin to male Lewis rats. Further, the model of rat adjuvant arthritis
      (AA) was used to evaluate the protective effect of stobadine dipalmitate against
      indomethacin-induced gastroenteropathy. Indomethacin was administered
      subcutaneously in the daily dose of 5, 7, 10, 20 and 30 mg/kg b.w. Survival of
      the animals and damage of gastric and intestinal mucosa were monitored, and some
      biochemical parameters were determined. In AA rats stobadine dipalmitate was
      administered orally in the daily dose of 15 mg/kg. For the chronical experiments
      on AA rats the subcutaneous indomethacin dose of 5 mg/kg was selected as the
      therapeutic dose and the dose of 7 mg/kg was chosen as the adequate dose for
      gastropathy induction. The additive adverse effect of arthritis induction and
      indomethacin administration was demonstrated on the basis of gastric mucosa
      damage observations. The supposed stobadine gastro-protection was not confirmed.

PMID- 15141963
TI  - Some lung cellular parameters reflecting inflammation after combined inhalation
      of amosite dust with cigarette smoke by rats.
AB  - Cellular changes were followed in lung cell suspensions after 175 day inhalation
      by rats of concentrations 30 mg/m3 or 60 mg/m3 of amosite asbestos every second
      day combined with daily exposure to cigarette smoke at 30 mg of total particulate
      matter (TPM)/m3 air. Concomitantly, lung inflammation was assessed by changes in
      the bronchoalveolar lavage fluid (BALF). A dose-dependent rise in the BALF
      inflammatory parameters was found. The rise of the proportion of binucleate (BNC)
      and multinucleate cells (MNC) in lung cell suspensions was also dose-dependent.
      It is concluded that, in the experimental assessment of effects of fibrogenic
      dusts, the number of BNC and of MNC in lung cell suspensions may serve as a
      useful semiquantitative biomarker of the inflammation.

PMID- 15141964
TI  - Possible genotoxic risk of combined exposure to pharmaceutical coal tar and UV-B
      radiation.
AB  - Goeckerman's therapy of psoriasis combines exposure to pharmaceutical coal tar
      and UV-B radiation. In the pilot study (15 patients had been diagnosed with
      psoriasis, the average time period in hospital therapy was 24 days, the average
      age of the patients was 29 years, 47% of them were smokers) a level of genotoxic
      risk from therapy was evaluated by using chromosomal aberration of peripheral
      lymphocytes. The study suggested the presence of an increased genotoxic risk from
      the therapy. The PASI scores (Psoriasis Area and Severity Index) were monitored.

PMID- 15141966
TI  - Protection of newborn organism against effect of oxidative stress.
AB  - OBJECTIVE: The aim of the present study was to investigate influence of oxidative
      stress on newborn organism, in terms of the dynamics of malondialdehyde (MDA)
      concentration changes and of the activities of selected antioxidants in asphyxial
      newborns on the 1st and 5th day of life. METHOD: In the group of 62 preterm and
      term asphyxial newborns, characterized by the presence of asphyxial criteria and
      admitted within 24 hours of life, the plasma concentration of MDA and level of
      total antioxidant status (TAS) were followed. RESULTS: Dynamic changes of MDA
      signalized active process of lipoperoxidation (LP) and values of TAS were
      decreased in comparison with the capacity of adult patients.

PMID- 15141965
TI  - Kojic acid and its derivatives: history and present state of art.
AB  - Kojic acid (5-hydroxy-2-hydroxymethyl-4-pyranone) represents an attractive
      polyfunctional skeleton for development of biologically active compounds. The
      authors prepared a great variety of kojic acid derivatives and selected
      biological properties have been studied. Thus, kojic acid derivatives are
      promising compounds that might advantageously be used in human and/or veterinary
      medicine and also in preparation of new, even more biologically active
      preparations.

PMID- 15141967
TI  - Evaluation of bronchoalveolar lavage fluid cytotoxic parameters after inhalation
      exposure to amosite and wollastonite fibrous dusts combined with cigarette smoke.
AB  - The aim of this work was to compare the influence of amosite-asbestos and
      wollastonite fibrous dusts combined with cigarette smoke on chosen cytotoxic
      parameters of bronchoalveolar lavage fluid (BALF) in rats. Fisher 344 rats
      inhaled wollastonite or amosite fibrous dusts (60 or 30 mg x m(-3) air) one hour
      every two days combined with daily breathing of diluted mainstream tobacco smoke
      (30 mg of TPM x m(-3) air). The experiment lasted 6 months. After sacrifying the
      animals bronchoalveolar lavage (BAL) was performed and the viability and
      phagocytic activity of alveolar macrophages (AM), lactate dehydrogenase (LDH) and
      alkaline phosphatase activity (in the cell-free BALF), acid phosphatase (ACP) and
      cathepsin D activity (in cell-free BALF and BAL cell suspension) were examined.
      Exposure to amosite without tobacco smoke significantly decreased the viability
      of AM and increased the cathepsin D activity in BAL cells. Exposure to
      wollastonite significantly increased only the cathepsin D activity in BAL cells.
      Smoking significantly depressed the phagocytic activity of AM and amplified the
      amosite-induced increase of lysosomal enzyme activities--especially the activity
      of cathepsin D in BAL cells.

PMID- 15141968
TI  - Effect of melatonin on neurobehavioral dysfunctions induced by intrauterine
      hypoxia in rats.
AB  - Intrauterine hypoxia associated with oxidative stress represents an important
      risk factor for development of neurobehavioral dysfunctions. In the present
      study, we investigated the potential protective effect of melatonin (MEL) on
      neurobehavioral dysfunctions induced by chronic intrauterine hypoxia in rats by
      the anticonvulsant drug phenytoin (PHT), which is known by its teratogenic
      potential. Pregnant female rats (Wistar/DV) were orally treated by PHT (150
      mg/kg) from day 7 to 18 of gestation. MEL was dissolved in drinking water (40
      microg/ml) and administered from day 0 to 19 of gestation. Neurobehavioral
      development of offspring was evaluated from birth up to day 90 of postnatal life.
      The results of the study confirmed the high behavior-teratogenic potential of
      PHT. Prenatal administration of PHT resulted in delayed neuromotor and reflex
      development, decreased exploration in the open field, abnormal "circling" and
      impaired performaces in water maze. Co-administration of MEL failed to have any
      effect on neurobehavioral dysfunctions induced by PHT treatment. Even
      administration of MEL alone caused developmental alterations in offspring
      manifested by accelerated testes descent and delayed onset of negative geotaxia
      and startle reflex. The results suggest to pay increased attention to MEL
      concerning its exogenous use during pregnancy.

PMID- 15141969
TI  - The effect of estradiol on the oxidative damage and trace element level
      determined in the liver of rats treated with dimethylarsinic acid.
AB  - DMA--dimethylarsinic acid (cacodylic acid)--used as an herbicide, is the major
      metabolite formed after the exposure to inorganic arsenics in mammals. It is
      considered to have an important role in arsenic carcinogenesis through the
      induction of oxidative damage in various tissues. Estradiol, apart from its main
      hormonal effect, displays both prooxidative and antioxidative action depending on
      the condition of the treatment. The oxidative stress plays a crucial role in
      estrogen-induced carcinogenesis. In the experiments performed in female Wistar
      rats receiving drinking water ad libitum with 0.01% DMA for 10 weeks, one half of
      rats was treated with 17beta-estradiol (0.1 mg/rat s.c., twice a week) starting
      the 3rd week. One more group received estradiol only and last group served as
      controls receiving drinking water without treatment. The DMA enhanced lipid
      peroxidation in the liver, estradiol treatment potentiated this effect of
      arsenic. The GSH level was enhanced in DMA+estradiol treated group. In estradiol
      only treated group both the lipid peroxidation and GSH content were increased.
      The administration of estradiol caused an enhancement of several trace element
      concentrations in the liver, mainly that of iron and copper. The critical role of
      estrogen on the development of oxidative stress was thus proved.

PMID- 15141970
TI  - Antioxidants--clinical aspects.
AB  - Interest in nutrition and food consumption in advanced countries has become an
      important instrument of active care for maintaining the population's health.
      Basic orientation in food composition and in topical knowledge about the
      effectiveness of individual nutrients in the human organism form an indispensable
      part of nutrition and health consciousness and it can significantly facilitate
      and improve activity in both professionals and non-professionals, or it can
      correct some subjective opinions and deep-rooted imaginations. At the end of the
      last century progress in molecular biological research led to better knowledge
      about previously unknown functions of nutrients in the metabolism and also
      knowledge about relationships among the individual nutrients. The interest of
      research institutes was concentrated on selected nutrient groups and also on
      vitamins. Attention was focused on verification of the role of vitamin E and beta
      carotene in strengthening the antioxidative capacity of the organism and immunity
      system as prevention against degenerative diseases, atherosclerosis and tumorous
      diseases. Attention was attracted to the fact that folacin acts preventively
      against defects of the neural tube and against hyperhomocysteinemia as an
      independent atherosclerosis risk factor. Also the data about the organism's
      needs, for example vitamins, are mostly not quite complete, especially in the
      sphere of detailed knowledge of their preventive effect concerning the so-called
      civilization diseases, their use in the organism and the reaction of the organism
      to their insufficient or redundant supply.

PMID- 15141971
TI  - Phototoxic activity and the possibilities of its testing.
AB  - The photodynamically active compounds have been attracting an attention of
      specialists for relatively long time. The most fruitful period of their research
      has been probably the last decade. The structures of the photosensitizers are
      very different. The biological activity is based on a formation of free reactive
      radicals after an excitation of the molecules of the phototoxins by e.g. UV
      radiation. Some photosensitizers are used for treatment of various diseases in
      dermatology and oncology. Since the substances can occur in plants, food or
      cosmetics, the photodynamic activity of these compounds is necessary to be
      studied under various conditions. Now e.g. some photochemical reactions, cell
      cultures, cultures of microorganisms, suspensions of erythrocytes, and different
      species of animals are used to the research of the photodynamic activity of the
      substances.

PMID- 15141972
TI  - On augmentation of adenosine-mediated negative dromotropic effect by K+ released
      during myocardial ischemia.
AB  - The present study was designed to investigate mechanisms of adenosine (ADO)
      mediated prolongation of conductivity through the atrioventricular (AV) node
      during myocardial ischemia. Using the Langendorff preparation of the guinea pig
      heart, we tested the hypothesis that extracellular potassium concentration
      elevated due to ischemia could augment ADO effect. Exposure of the heart
      preparation to either stop-flow or hypoxic Krebs-Henseleit solution (KH)
      inhibited AV node conductivity observed as an increase in SH interval, and
      finally resulted in AV block. Superficial potassium concentration ([K+]s),
      recorded simultaneously increased in response to each stop-flow or hypoxia.
      Application of 0.1 mM BaCl2 markedly increased the SH interval, yet it did
      neither protect the heart from hypoxia-evoked AV block nor did it prevent hypoxia
      induced [K+]s elevation. Neither did perfusion of the myocardium with modified KH
      containing 8 mM K+ affect the hypoxic AV block and [K+]s increase. The hypoxic
      effects were not affected by adenosine A1 agonist N6-cyclopentyl-adenosine (CPA,
      30 nM). In the presence of CPA, application of high-K+ KH, where potassium was
      elevated to the value of hypoxic level, did not affect the SH interval. On the
      other hand, adenosine deaminase (ADA, 4 U/ml) significantly attenuated the
      hypoxic AV block. This indicated an involvement of endogenous ADO. Yet, in the
      presence of both ADA and CPA, the application of the high-K+ KH did not affect
      the SH interval. We concluded that increased extracellular [K+], elevated due to
      hypoxia, did not participate in the hypoxia-induced AV block mediated by ADO.

PMID- 15141973
TI  - The influence of low-level sarin inhalation exposure on the host resistance and
      immune reaction of inbred BALB/c mice after their infection with Francisella
      tularensis LVS.
AB  - To study the influence of low-level sarin inhalation exposure on immune
      functions, inbred BALB/c mice were exposed to two low concentrations of sarin for
      60 minutes in the inhalation chamber and then infected with Francisella
      tularensis LVS on the 7th day following the exposure to sarin. 24 hours after
      infection, the level of some isotypes of antibodies (IgM, IgA) against tularaemia
      was significantly decreased regardless of the sarin concentration used while the
      lymphoproliferation was significantly increased regardless of the mitogen and
      sarin concentration used. Later, the level of some isotypes of antibodies (IgM,
      IgA) against tularaemia and the vitality of Francisella tularensis LVS was
      significantly increased in the case of exposure of mice to clinically symptomatic
      concentration of sarin (7 days after infection) while the lymphoproliferation was
      significantly decreased regardless of the concentration of sarin when specific
      tularaemic antigen Ag4 was used as a mitogen (3 weeks after infection). Thus, the
      results indicate that not only symptomatic but also asymptomatic dose of sarin is
      able to alter the host resistance and reaction of immune system, especially at 24
      hours and 7 days following infection with Francisella tularensis LVS.
      Nevertheless, the alteration of immune functions following the inhalation
      exposure to a symptomatic concentration of sarin seems to be more pronounced.

PMID- 15141974
TI  - Antiradical activity of petals of Philadelphus coronarius L.
AB  - 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay and nitroprusside assay were used for
      in vitro study of antiradical/scavenger activity of Philadelphus coronarius petal
      substances. The results obtained can be used as the basis for further studies of
      this type of the biological effects in the plant.

PMID- 15141975
TI  - Effects of kojic acid on oxidative damage and on iron and trace element level in
      iron-overloaded mice and rats.
AB  - Since members of hydroxypyrone series posses iron chelating properties, kojic
      acid (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-one, a fungal metabolite of
      natural origin, has been suggested to might play a role in iron-overload diseases
      and in oxidative stress conditions involving transition metal. In our experiments
      in vivo models of iron-overload were used to study iron-chelating properties of
      KA and its effect on oxidative damage in mice and rats. The treatment of iron
      preloaded rats (25 mg Fe x kg(-1) b.w., i.p., daily for five days) with 0.5% KA
      in drinking water for four weeks did not lower the iron concentration accumulated
      in the liver, neither diminished the induced hepatic lipid peroxidation in iron
      loaded rats. The GSH level decreased in KA-treated group. Similarly, in iron
      loaded mice model experiment, the following oral treatment with KA (100 mg x kg(
      1)) daily for 7 days did not decrease the level of Fe accumulated in the liver
      and the lipid peroxidation even enhanced after KA treatment. Though in our
      experiments in vivo the ability of kojic acid to affect iron kinetics in the
      organism could not be proved, kojic acid as a molecule of natural origin may
      serve as a template for the preparation of new biologically active derivatives
      possessing capability of chelating iron.

PMID- 15141977
TI  - Acute experimental tabun-induced intoxication and its therapy in rats.
AB  - Pharmacological pretreatment and antidotal treatment on tabun-induced
      neurotoxicity were studied in male albino rats that were poisoned with a lethal
      dose of tabun (280 microg/kg i.m.; 100% of LD50 value) and observed at 24 hours
      and 7 days following tabun challenge. The neurotoxicity of tabun was evaluated
      using a Functional observational battery and an automatic measurement of motor
      activity. Pharmacological pretreatment as well as antidotal treatment were able
      to reverse most of tabun-induced neurotoxic signs observed at 24 hours following
      tabun poisoning. However, there was not significant difference between the
      efficacy of profylaxis and antidotal treatment to eliminate tabun-induced
      neurotoxicity. The combination of profylactic pretreatment and antidotal
      treatment seems to be slightly more effective in the elimination of tabun-induced
      neurotoxicity in rats at 24 hours following tabun challenge in comparison with
      the administration of profylactic pretreatment or antidotal treatment alone. At 7
      days following tabun poisoning, very few neurotoxic signs in tabun-poisoned rats
      were observed regardless of administration of pharmacological pretreatment or
      antidotal treatment. Thus, our findings confirm that the combination of
      pharmacological pretreatment and antidotal treatment is not only able to protect
      the experimental animals from the lethal effects of tabun but also to eliminate
      most of tabun-induced signs of neurotoxicity in tabun-poisoned rats.

PMID- 15141976
TI  - The effect of fibrous dusts on lung cells. In vitro study.
AB  - The mechanism of toxicity of selected asbestos substitute mineral fibres was
      examined and compared to that of asbestos. Alveolar macrophages and type II cells
      were isolated from Fischer 344 rats and after 20 h cultivation various
      concentration of fibres alone (amosite, wollastonite, rockwool or glass fibres)
      or in combination with cigarette smoke were added to cells and the cultivation
      continued for another 24 h. After finishing the exposure the number of alkaline
      phosphatase positive type II cells was counted, the comet assay was used to
      detect DNA damage (strand breaks) in both cell types and ultrastructural changes
      were evaluated by transmission electron microscopy. The decrease of the number of
      alkaline positive type II cells was dose dependent in all cases. The number of
      DNA strand breaks (SBs) in both cell types was enhanced after exposure to all
      types of fiber, the enhancement was dose dependent, the highest level of SBs was
      observed after amosite exposure. The combined exposure to mineral fibres and
      cigarette smoke showed synergic effect on the level of SBs. Transmission electron
      microscopy showed that already 1 microg x cm(-2) amosite caused destruction of AM
      while other fibres were phagocytized.

PMID- 15141978
TI  - The new therapy procedures for viper attack.
AB  - In Slovak Republic and the region of Central and Eastern Europe the viper is the
      only species of venomous snake living in wild. During the last nine observed
      years (1993-2002) the Toxicological Information Center (TIC) was consulted in 81
      cases of individuals attacked by snakes. 51 of these cases were by viper,
      rattlesnake 6, and green mamba once. 23 cases were by non-venomous snakes; adder
      22 times and royal snake once. The viper and adder attacks occurred in the wild
      and the other cases with snake keepers. None of affected individuals died. Our
      contribution contains the new recommended therapy procedures for viper attack.

PMID- 15141979
TI  - Amphotericin B, its lipid formulations and conjugates with polymers.
AB  - The minireview is focused on novel findings concerning mechanism of action, lipid
      formulations, polymer conjugates, and structural modifications of amphotericin B.

PMID- 15141980
TI  - Biological activity of 2-hydroxythiobenzanilides and related compounds.
AB  - Thiobenzanilides substituted in thioacyl moiety with one or more hydroxy groups
      are interesting for their biological effects depending on the substitution
      pattern. New findings in mechanisms of action of 2-hydroxybenzanilides insert 2
      hydroxybenzanilides and their analogues, e.g. substituted thiobenzanilides, among
      interesting compounds in the development of new potential antimicrobial drugs.
      The present review paper with 32 references links up with our previous
      communications which reviewed biological activity of 2-hydroxybenzanilides and
      related compounds, and includes the research of mono-, di-, and
      trihydroxythiobenzanilides carried out in the last period.

PMID- 15141981
TI  - In vitro reactivation of tabun-inhibited acetylcholinesterase using new oximes-
      K027, K005, K033 and K048.
AB  - Four new AChE oximes for reactivation of acetylcholinesterase inhibited with
      tabun - K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)
      propane dibromide], K005 [1,3-bis(2-hydroxyiminomethylpyridinium) propane
      dibromide], K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide] and
      K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane
      dibromide] were prepared. Their efficacies to reactivate tabun-inhibited
      acetylcholinesterase were studied and compared with the currently used
      acetylcholinesterase reactivators (pralidoxime, obidoxime and HI-6). Reactivator
      K048 seems to be promising reactivator of tabun-inhibited AChE. Its reactivation
      potency is significantly higher than the efficacy of HI-6 and pralidoxime, and
      comparable with the potency of the obidoxime at human relevant doses.

PMID- 15141982
TI  - Inhibitory effect of cadmium and tobacco alkaloids on expansion of porcine oocyte
      cumulus complexes.
AB  - Studies aimed at the influence of smoking on reproductive functions have found
      out fertility disorders in smokers occurring at any stage of reproductive
      processes. In our experiments the role of cadmium, nicotine and anabasine was
      investigated in the expansion of oocyte-cumulus complexes (OCC) isolated from
      large antral porcine follicles. Suppression of FSH-induced cumulus expansion and
      significant inhibition of synthesis and accumulation of hyaluronic acid in the
      cell/matrix compartment of the OCC was observed in the presence of different
      concentrations of tested compounds. The suppressive effect of cadmium and tobacco
      alkaloids on the cumulus expansion was accompanied by decreased progesterone
      production by cumulus cells during 42 h incubation of the OCC with FSH.

PMID- 15141983
TI  - Antioxidant vitamin pool in senior population.
AB  - AIM: To compare plasma concentration of alpha-tocopherol and ascorbic acid in
      healthy seniors (age over 65 years), senior patients with either diabetes
      mellitus, acute myocardial infarction or dyslipidemia and recommended values of
      these vitamins. METHODS: Studied groups included 30 patients with diabetes
      mellitus (DM); 30 patients 1 - 2 weeks after acute myocardial infarction (AMI);
      11 patients with lipid metabolism disorder (LD, total cholesterol > 6.2 mM); and
      control group of 27 healthy persons. RESULTS: Concentration of alpha-tocopherol
      in DM group was 14.6 +/- 5.3 microM, in AMI group 13.7 +/- 5.6 microM, in LD
      group 15.9 +/- 5.6 microM and in control group 12.9 +/- 4.1 microM. No
      statistically significant differences were found. However, comparison of
      determined values with levels recommended for prevention revealed remarkable low
      plasma concentration of alpha-tocopherol in the Czech population. Plasma
      concentration of ascorbic acid in DM group was 47.07 +/- 22.80 microM, in AMI
      group 33.15 +/- 12.81 microM, in LD group 45.59 +/- 23.02 microM and in control
      group 43.28 +/- 26.57 microM. No statistically significant differences were found
      between the controls and individual groups of patients. Plasma concentrations of
      vitamin C reached the recommended value in all cases except the AMI group, where
      it was significantly lower. CONCLUSION: Seniors in the Czech population were
      proved to be significantly short of alpha-tocopherol, minor shortage of vitamin C
      was found only in group of patients with myocardial infarction.

PMID- 15141984
TI  - Effect of melatonin on biochemical variables induced by phenytoin in organs of
      mothers, foetuses and offsprings of rats.
AB  - The present pre- and postnatal study was carried out to investigate the effect of
      melatonin (MEL), a potent antioxidant, on biochemical variables in the in vivo
      model of intrauterine hypoxia in rats. Chronic hypoxia was induced
      pharmacologically by the administration of the anticonvulsant phenytoin (PHT)
      during pregnancy. Rats were orally treated by PHT (150 mg/kg) from day 7 to 18 of
      gestation. MEL in drinking water (40 microg/ml) was administered from day 0 to 19
      of gestation. The activity of the lysosomal enzyme N-acetyl-beta-D
      glucosaminidase (NAGA) and the level of glutathione (GSH) were used as markers of
      tissue damage. In the prenatal study PHT-induced toxic damage was associated with
      an increase in NAGA activity and decrease of GSH level in placenta and in
      maternal serum and heart. MEL partially inhibited the changes of NAGA activity
      given above. MEL was able to increase only the decreased level of GSH in maternal
      heart. PHT decreased the level of GSH and increased the activity of NAGA in
      foetal organs, the improvement occurred in the liver and lungs, but not in foetal
      brain. In the postnatal study a significant increase of liver GSH level was found
      in all (control, MEL, PHT, MEL+PHT) groups of 1-day-old pups, while the activity
      of NAGA remained unchanged. We did not observe any significant differences in
      NAGA activity in the lungs and heart of pups. MEL increased the GSH level in
      lungs and heart. We concluded that administration of MEL during pregnancy
      partially inhibited the biochemical changes induced by PHT.

PMID- 15141985
TI  - Gut and vessel alterations induced by mesenteric ischaemia/reperfusion in rats.
AB  - A rat model of transient occlusion of the superior mesenteric artery was used to
      study the intestinal and vascular injury induced by ischaemia/ reperfusion (I/R).
      A pronounced intestinal injury was observed, ranging from hyperaemia to severe
      haemorrhagic necrosis and bleeding. The length of the damaged intestinal segments
      reached 58.6% of the small intestine with a decrease of the wet weight in the I/R
      group. Sham operation resulted in 100% survival, I/R decreased survival to 40%
      after 24 h. Following I/R a significant increase of vascular permeability was
      observed in the small intestine. Gamma-glutamyl transpeptidase activity decreased
      aborally in sham operated rats and I/R reduced it further in all parts of the
      small intestine. I/R resulted in damaged endothelium-dependent relaxation of
      mesenteric artery rings. This was manifested by decreased maximal responses of
      arterial preparations to acetylcholine as well as decreased pD2 values. The
      results confirmed and specified the presumed effect of I/R on the small intestine
      and on vascular functions.

PMID- 15141987
TI  - Chemical agents and chemical terrorism.
AB  - Chemical terrorism is a new threat to the security of mankind, which scale
      essentially exceeds the impact of use of the most modem firearms. At present time
      all over the world threats from different radical elements to use radioactive
      materials, potent poisonous substances and pathogenic microorganisms for
      terrorist purposes became more frequent. High-toxic chemical substances can fall
      in terrorist hands through wide range of sources. Potentially misused types of
      chemical compounds are discussed in this article.

PMID- 15141986
TI  - Mutagenicity of airborne particulate matter PM10.
AB  - Mutagenic activity of extractable organic matter (EOM), from airborne particles
      collected over winters in four towns of Czech Republic, was investigated by the
      means of Salmonella typhimurium indicator strains TA98 and YG1041 using the Ames
      plate incorporation assay. Mutagenicity of all tested samples showed significant
      dose-related increase in number of revertants per mg of EOM. The direct mutagenic
      potency detected with TA98 increased further in the presence of external
      metabolic activation. The mutagenic potency detected with YG1041 was about two
      orders of magnitude higher than that detected with TA98. The mutagenicity results
      correlated with the concentrations of the polycyclic aromatic hydrocarbons (PAHs)
      determined by GC/MS. Local differences in mutagenicity, expressed as numbers of
      revertants per m3 of air, were observed with the highest values in Prague air
      samples. For routine ambient air mutagenicity monitoring, the use of YG1041 and
      the plate incorporation test are recommendable.

PMID- 15141988
TI  - Acute toxicity of binary mixture benzene-ethanol and partition coefficient K(ow)
      of benzene and ethanol.
AB  - The study related to partition coefficients between n-octanol and water of
      compounds in binary mixture benzene-ethanol was carried out. Partition
      coefficients of benzene and ethanol for different values of molar ratio of
      benzene in the mixture were determined. Collected results show statistically
      significant deviations the K(ow) of benzene for some molar ratios (0.2 to 0.6)
      from values for pure compound. For ethanol, there are no statistically
      significant deviations from values for pure compound, however there are some
      trends of changes of K(ow).

PMID- 15141989
TI  - Relationship between plasmatic levels of sarin and cholinesterase inhibition in
      rats exposed to sarin vapors.
AB  - In our study we monitored plasmatic levels of sarin and changes in cholinesterase
      activities in rats after exposure to sarin vapors at low concentration. Rats were
      exposed to sarin in inhalation chamber at concentration 1.25 or 2.5 microg/l for
      60 minutes. The acetylcholinesterase activity was measured in erythrocytes and in
      different brain regions (frontal cortex--FC, pontomedullar area--PM, basal
      ganglia--BG). Butyrylcholinesterase activity and sarin levels were measured in
      plasma. Acetylcholinesterase activity in erythrocytes as well as
      butyrylcholinesterase activity in plasma were significantly decreased in both
      groups of animals after intoxication with sarin. In brain, the significant
      decrease in acetylcholinesterase activity was measured in FC and PM for both
      groups. In group exposed to higher concentration of sarin vapors, the plasmatic
      level of sarin was nearly 2 x higher than in group exposed to sarin at
      concentration 1.25 microg/l. The linear dependence between plasmatic levels of
      sarin and AChE activity was assayed in FC region of brain and in erythrocytes,
      exponential relationship in PM region of brain and for BuChE activity in plasma.

PMID- 15141990
TI  - Effect of melatonin and stobadine on maternal and embryofoetal toxicity in rats
      due to intrauterine hypoxia induced by phenytoin administration.
AB  - The aim of the present study was to test the hypothesis that the natural
      antioxidant melatonin (MEL) and the synthetic antioxidant stobadine (STO) could
      reduce the incidence of maternal and embryofoetal toxicity in rats due to
      intrauterine hypoxia. Chronic hypoxia was induced pharmacologically by the
      administration of the anticonvulsant phenytoin (PHT) during the entire period of
      pregnancy. PHT disturbed the normal course of pregnancy, affected reproductive
      parameters and increased the incidence of skeletal anomalies. MEL did not protect
      the PHT-induced development toxicity in rat. On the other hand, STO partially
      prevented PHT-induced reduction of foetal and placental weights. Administration
      of STO also decreased the frequency of pre- and post-implantation loss and
      resorptions in the PHT group. We concluded that pretreatment of pregnant rats
      with STO prevented to a certain extent reproductive and foetal development
      alterations caused by chronic intrauterine hypoxia.

PMID- 15141991
TI  - Determination of acrylonitrile in materials in contact with foodstuffs.
AB  - Monitoring of the content of free acrylonitrile in plastics used for the
      preparation of viands is necessary due to its negative effect on human health. A
      content of 20 ppb is the maximal value of free acrylonitrile in such samples. In
      this case, head-space gas chromatography is most favourable analytical method
      when combined with the standard addition method together with a mass-spectrometry
      detector because of a very low concentration of the analyte. In samples taken for
      analysis, the content of free acrylonitrile was found to be within 5.1 and 10.3
      ppb (microg/kg).

PMID- 15141992
TI  - Tubifex tubifex Mull.--photosensitive organism.
AB  - The worm Tubifex tubifex Mull. (Tubificideae, Oligochaeta) is a suitable organism
      for the research of the biological effect of various pollutants. This pilot study
      deals with the responds of the organism to the treatments of two photosensitizers
      (bengal rose B, quinidine) and UVA radiation. The activity of the
      photosensitizers was evaluated by the comparison of the surfaces of tested worms
      and dark controls. The results showed that T. tubifex Mull. could be a suitable
      organism for the studies of phototoxicity. This species demonstrated relatively
      strong sensitivity to the effect of the selected photodynamically active
      substances.

PMID- 15141993
TI  - Surprises and omissions in toxicology.
AB  - The paper describes expected and unexpected results gained from studies performed
      decades ago, and so to say - forgotten. 1. Different bacterial toxins can induce
      considerable changes in pharmacokinetics and pharmacodynamics of applied drugs.
      To admit clinical trials, only results from healthy human volunteers are
      required, however. 2. Antagonists to the toxicity of bacterial toxins in general
      have to be administered prior to the toxin. However, adenosine triphosphate (ATP)
      is effective also when applied after toxins. ATP is "in" again in contemporary
      research. 3. A controlled clinical trial revealed substantial differences between
      the D- and D,L-form of cycloserin. 4. The antimetabolite 6-azauracil riboside and
      eventually its triacetate derivative was claimed to possess antitumor properties.
      However, a controlled clinical trial did not confirm its potency in this aspect.
      On the other hand, the tolerance was excellent. This finding encouraged clinical
      trials in psoriasis, a disease of autoimmune etiology. Moreover, beneficial
      effects and tolerance of the compound was described in herpes zoster and even in
      smallpox. On the basis of these results a controlled clinical trial in rheumatoid
      arthritis, also judged to be an autoimmune disease, was started. Because of early
      high toxicity, the study was discontinued. 5. High doses of the compound induce
      ocular lesions in animals. The above examples justify the titel of this paper.

PMID- 15141994
TI  - A mechanistic perspective on the specificity and extent of COX-2 inhibition in
      pregnancy.
AB  - Cyclo-oxygenase (COX)-2-specific inhibitors form one of the most commonly
      prescribed groups of pain relief drugs. Despite the known reproductive toxicity
      of NSAIDs, which are nonspecific COX inhibitors, little is known about the
      differential role between COX-1 and COX-2 inhibition on reproduction. It has been
      suggested that COX-2 plays a prominent role in animals at all stages of
      reproduction, from ovulation to implantation to decidualisation and delivery.
      Both estrogen and progesterone have been shown to be involved in regulation of
      COX production in tissues of the reproductive tract. Similar to NSAIDs, warnings
      on reproduction have been included in the product labelling of marketed COX-2
      specific inhibitors. Variations in the level of warnings in these labels are
      noted, with an order of stringency being celecoxib approximate, equals etoricoxib
      > rofecoxib approximate, equals valdecoxib. The specificity of etoricoxib for COX
      2 has been found to be approximately 3-fold greater than that of rofecoxib and
      valdecoxib and approximately 14-fold more than celecoxib in human whole blood
      assays. There is growing evidence to suggest that the inducible COX-2, rather
      than the COX-1, is the main enzyme responsible for reproduction. It was
      demonstrated that the change in estrogen and progesterone levels during pregnancy
      contributes to the dramatic increase in COX-2 expression. This further
      strengthens the earlier findings that COX-2 activities are necessary to support
      pregnancy. It is also worth mentioning that although a definite correlation
      between the specificity of a COX-2-specific inhibitor and the level of precaution
      stated in the drug labels in UK was not obtained, a direct relationship between
      the specificity and the potential to result in teratogenicity has not been
      excluded. With growing interest of the pharmaceutical industry in developing more
      COX-2-specific inhibitors and the fact that reproductive toxicity is not tested
      in pregnant women before marketing, it is important for drug regulators to raise
      awareness of the potential reproductive adverse effects and provide guidance on
      the level of caution when using these drugs in pregnancy.

PMID- 15141995
TI  - Do some inhibitors of COX-2 increase the risk of thromboembolic events?: Linking
      pharmacology with pharmacoepidemiology.
AB  - Inhibitors of the cyclo-oxygenase (COX)-2 isoenzyme were developed with the
      expectation that their use would be accompanied by a reduction in adverse
      reactions thought to be mediated through COX-1 compared with conventional
      nonselective NSAIDs. However, the results of some clinical studies and other
      evidence have led to the hypothesis that use of COX-2 inhibitors may contribute
      to an increased risk of adverse thromboembolic (TE) events. In this review, we
      have evaluated the evidence from small-scale in vitro and in vivo pharmacological
      studies, clinical trials and large-scale pharmacoepidemiological studies and
      commented on the relationship between the pharmacological characteristics related
      to thromboembolic events and the clinical effects in large-scale clinical trials
      and pharmacoepidemiological studies. Overall, the pharmacological evidence
      suggests that a prothrombotic effect of COX-2 selective inhibitors is plausible.
      To date, despite the results from the Vioxx Gastrointestinal Outcome Research
      (VIGOR) study from which the clinical concern regarding cardiovascular TE risk
      arose, the published data from other randomised controlled trials (RCTs),
      retrospective observational studies and spontaneous reporting schemes provide a
      conflicting body of evidence on the TE risk with COX-2 inhibitors. Concerns that
      COX-2 inhibitors may be associated with prothrombotic effects remain and these
      need to be addressed in large scale, RCTs designed specifically to investigate
      the possibility of an excess of adverse cardiovascular outcomes in users of some
      or all selective COX-2 inhibitors, both with and without concomitant low-dose
      aspirin (acetylsalicylic acid). Consideration must also be given to other
      pathophysiological mechanisms for potential cardiovascular risk linked with
      inhibition of COX-2. In view of the evidence reviewed, it is recommended that
      selective COX-2 inhibitors should be prescribed with caution, only in patients
      with conditions for which these drugs have proven efficacy and with careful
      monitoring of outcomes and adverse events. This is particularly important in the
      elderly, in patients with cardiovascular/renal disease and in patients with other
      risk factors that might predispose them to adverse events.

PMID- 15141998
TI  - Comparison of measured and predicted residual lung volume in determining body
      composition of collegiate wrestlers.
AB  - This investigation compared percent fat obtained via underwater weighing using
      measured and predicted residual lung volume (RLV) in euhydrated and hypohydrated
      collegiate wrestlers (N = 67). RLV was measured using O(2) rebreathing or O(2)
      dilution and predicted using 3 equations-Equation 1: (0.019 x height [cm]) +
      (0.0115 x age [years]) - 2.24; Equation 2: (0.017 x age [years]) + (0.06858 x
      height [in.]) - 3.477; and Equation 3: (0.0275 age [years]) + (0.0189 height
      [cm]) - 2.6139. Percent fat determined using RLV Equation 2 did not differ from
      the value obtained using measured RLV in the euhydrated (10.9 +/- 5.1 vs. 11.5 +/
      5.6% fat) or hypohydrated (10.8 +/- 5.1 vs. 12.3 +/- 5.6% fat) trials. All other
      percent fat values differed (p < 0.05) from the value obtained using measured RLV
      in euhydrated subjects. The use of RLV Equation 2 may be a practical alternative
      to measured RLV in determining percent fat in euhydrated and hypohydrated
      collegiate wrestlers.

PMID- 15141997
TI  - Evaluation of the extent of under-reporting of serious adverse drug reactions:
      the case of toxic epidermal necrolysis.
AB  - INTRODUCTION: Toxic epidermal necrolysis (TEN) is a life-threatening adverse drug
      reaction (ADR) that is primarily the result of drug exposure (incidence 0.4-1.3
      per million person-years). Life-threatening ADRs such as TEN should be reported
      to ADR monitoring programmes, which collect reports for suspected ADRs and alert
      the public and medical practitioners to new drug hazards. In Canada, reports are
      made to the Canadian Adverse Drug Reaction Monitoring Program (CADRMP).
      OBJECTIVE: To examine the extent of under-reporting for TEN in Canada. DESIGN: A
      retrospective case series design was used to collect all TEN cases for the period
      January 1995 to December 2000. METHODS: The CADRMP and 22 burn centres across
      Canada were contacted for all TEN patients treated during the specified time
      period. PATIENT GROUPS STUDIED: The study population consisted of patients
      admitted to burn treatment sites across Canada, patient cases reported to the
      CADRMP and patient cases recorded by the Canadian Institute for Health
      Information (CIHI) hospital discharge summaries as the International
      Classification of Diseases Version 9 Clinical Modification (ICD-9-CM) code 695.1.
      RESULTS: Twenty-five TEN cases (six fatal) were reported to CADRMP from January
      1995 to December 2000. During this period, 14 (63.6%) burn treatment sites
      reported admission of 250 TEN cases. Hospital discharge summaries using the ICD-9
      CM code 695.1 indicated that 4349 cases were admitted to hospital during this
      time period and it was estimated that 15.5% (n = 674) of these cases were TEN.
      Using the burn facility data as the denominator, 10% (25 of 250) of TEN cases
      were reported to CADRMP. Using CIHI data as a denominator, only 4% (25 of 674) of
      TEN cases were reported to CADRMP. CONCLUSIONS: There is serious under-reporting
      of TEN. Lack of reporting of life-threatening ADRs can compromise population
      safety. There is a need to increase awareness of ADR reporting programmes.

PMID- 15141999
TI  - Conflicting effects of fatigue and potentiation on voluntary force.
AB  - The objective of this study was to investigate whether a warm-up consisting of a
      series of maximal contractions would augment the force and activation of
      subsequent leg extensor contractions. Both voluntary and evoked isometric
      contractions were tested to determine the mechanisms underlying the response.
      Nine subjects were tested for twitch, tetanic, submaximal (30%), and maximal
      voluntary contractile (MVC) properties before and after (1, 5, 10, and 15
      minutes) one to three 10-second MVCs. MVC force either did not change following 1
      2 MVCs or was depressed at 10 and 15 minutes after 3 MVCs. MVC activation was
      decreased (4.4-6.9%) throughout recovery, whereas submaximal contractions were
      minimally affected. Although overall, twitches were potentiated (15.5-19.8%)
      posttest, 3 MVCs had significantly greater twitch potentiation than 1 or 2 MVCs
      at 5 and 10 minutes. Results suggest that voluntary and evoked contractions
      respond differently to prior 10-second MVCs. In the present study, a warm-up
      routine of 1-3 MVCs of a 10-second duration did not enhance subsequent voluntary
      performance.

PMID- 15141996
TI  - Benefit-risk assessment of ciclosporin withdrawal in renal transplant recipients.
AB  - Ciclosporin is associated with significant toxicity, including nephrotoxicity,
      and with an increased risk of cardiovascular events. Many attempts have been made
      to wean patients from ciclosporin. Before the availability of new
      immunosuppressive drugs, the acute rejection rate observed after ciclosporin
      withdrawal did not permit the widespread use of withdrawal regimens even though
      meta-analysis did not show that they adversely affected patient or graft
      survival. Nevertheless, maintenance therapy with azathioprine and corticosteroids
      has not become routine practice. The introduction of mycophenolate mofetil and
      subsequently sirolimus has increased the number of clinical studies of the
      effects of ciclosporin withdrawal. In stable patients, this withdrawal is
      associated with a small but significant increase in the incidence of acute
      rejection episodes. Declining renal function and other forms of ciclosporin
      related toxicity have improved. However, this improvement was also observed when
      ciclosporin was only reduced (and not withdrawn), which did not increase the risk
      of acute rejection. More precise definition of the patients who could benefit
      from ciclosporin-withdrawal may help to optimise the immunosuppressive regimen in
      this setting. In patients with chronic allograft deterioration, ciclosporin
      withdrawal together with mycophenolate mofetil introduction has been shown to
      improve renal function significantly in many small studies, and a large
      prospective randomised study. For the time being, ciclosporin withdrawal is a
      good therapeutic option for patients with declining renal function and signs of
      chronic ciclosporin nephrotoxicity on renal biopsy. Finally, recent preliminary
      studies have reported the results of complete avoidance of calcineurin inhibitors
      after renal transplantation. These results are promising as regards the incidence
      of acute rejection, renal function and safety, but need confirmation in larger
      trials with a longer follow-up. Nevertheless, it has become clear that the
      concept of an immunosuppressive regimen with little or no nephrotoxicity after
      renal transplantation is more and more important and plays a crucial part in
      tailoring immunosuppression to the needs of specific patient populations.

PMID- 15142000
TI  - Effect of direct supervision of a strength coach on measures of muscular strength
      and power in young rugby league players.
AB  - The purpose of the present study was to examine the influence of direct
      supervision on muscular strength, power, and running speed during 12 weeks of
      resistance training in young rugby league players. Two matched groups of young
      (16.7 +/- 1.1 years [mean +/- SD]), talented rugby league players completed the
      same periodized resistance-training program in either a supervised (SUP) (N = 21)
      or an unsupervised (UNSUP) (N = 21) environment. Measures of 3 repetition maximum
      (3RM) bench press, 3RM squat, maximal chin-ups, vertical jump, 10- and 20-m
      sprints, and body mass were completed pretest (week 0), midtest (week 6), and
      posttest (week 12) training program. Results show that 12 weeks of periodized
      resistance training resulted in an increased body mass, 3RM bench press, 3RM
      squat, maximum number of chin-ups, vertical jump height, and 10- and 20-m sprint
      performance in both groups (p < 0.05). The SUP group completed significantly more
      training sessions, which were significantly correlated to strength increases for
      3RM bench press and squat (p < 0.05). Furthermore, the SUP group significantly
      increased 3RM squat strength (at 6 and 12 weeks) and 3RM bench press strength (12
      weeks) when compared to the UNSUP group (p < 0.05). Finally, the percent increase
      in the 3RM bench press, 3RM squat, and chin-up(max) was also significantly
      greater in the SUP group than in the UNSUP group (p < 0.05). These findings show
      that the direct supervision of resistance training in young athletes results in
      greater training adherence and increased strength gains than does unsupervised
      training.

PMID- 15142001
TI  - Combined creatine and sodium bicarbonate supplementation enhances interval
      swimming.
AB  - This study examined the effect of simultaneous supplementation of creatine and
      sodium bicarbonate on consecutive maximal swims. Sixteen competitive male and
      female swimmers completed, in a randomized order, 2 different treatments (placebo
      and a combination of creatine and sodium bicarbonate) with 30 days of washout
      period between treatments in a double-blind crossover procedure. Both treatments
      consisted of placebo or creatine supplementation (20 g per day) in 6 days. In the
      morning of the seventh day, there was placebo or sodium bicarbonate
      supplementation (0.3 g per kg body weight) during 2 hours before a warm-up for 2
      maximal 100-m freestyle swims that were performed with a passive recovery of 10
      minutes in between. The first swims were similar, but the increase in time of the
      second versus the first 100-m swimming time was 0.9 seconds less (p < 0.05) in
      the combination group than in placebo. Mean blood pH was higher (p < 0.01-0.001)
      in the combination group than in placebo after supplementation on the test day.
      Mean blood pH decreased (p < 0.05) similarly during the swims in both groups.
      Mean blood lactate increased (p < 0.001) during the swims, but there were no
      differences in peak blood lactate between the combination group (14.9 +/- 0.9
      mmol.L(-1)) and placebo (13.4 +/- 1.0 mmol.L(-1)). The data indicate that
      simultaneous supplementation of creatine and sodium bicarbonate enhances
      performance in consecutive maximal swims.

PMID- 15142002
TI  - Comparison of physical and performance characteristics of NCAA Division I
      football players: 1987 and 2000.
AB  - The purpose of this study was to compare normative data from present Division I
      National Collegiate Athletic Association football teams to those from 1987.
      Players were divided into 8 positions for comparisons: quarterbacks (QB), running
      backs (RB), receivers (WR), tight ends (TE), offensive linemen (OL), defensive
      linemen (DL), linebackers (LB), and defensive backs (DB). Comparisons included
      height, body mass, bench press and squat strength, vertical jump, vertical jump
      power, 40-yd-dash speed, and body composition. Independent t-tests were used to
      analyze the data with level of significance set at p < 0.01. Significant
      differences (p < 0.01) were found in 50 of 88 comparisons. From 1987 until 2000,
      Division I college football players in general have become bigger, stronger,
      faster, and more powerful. Further research is warranted to investigate if these
      trends will continue.

PMID- 15142003
TI  - Maximizing strength development in athletes: a meta-analysis to determine the
      dose-response relationship.
AB  - The efficiency, safety, and effectiveness of strength training programs are
      paramount for sport conditioning. Therefore, identifying optimal doses of the
      training variables allows for maximal gains in muscular strength to be elicited
      per unit of time and also for the reduction in risk of overtraining and/or
      overuse injuries. A quantified dose-response relationship for the continuum of
      training intensities, frequencies, and volumes has been identified for
      recreationally trained populations but has yet to be identified for competitive
      athletes. The purpose of this analysis was to identify this relationship in
      collegiate, professional, and elite athletes. A meta-analysis of 37 studies with
      a total of 370 effect sizes was performed to identify the dose-response
      relationship among competitive athletes. Criteria for study inclusion were (a)
      participants must have been competitive athletes at the collegiate or
      professional level, (b) the study must have employed a strength training
      intervention, and (c) the study must have included necessary data to calculate
      effect sizes. Effect size data demonstrate that maximal strength gains are
      elicited among athletes who train at a mean training intensity of 85% of 1
      repetition maximum (1RM), 2 days per week, and with a mean training volume of 8
      sets per muscle group. The current data exhibit different dose-response trends
      than previous meta-analytical investigations with trained and untrained
      nonathletes. These results demonstrate explicit dose-response trends for maximal
      strength gains in athletes and may be directly used in strength and conditioning
      venues to optimize training efficiency and effectiveness.

PMID- 15142004
TI  - Effect of training on the muscle strength and dynamic balance ability of adults
      with down syndrome.
AB  - The purpose of this study was to evaluate the effect of training on the muscle
      strength and dynamic balance ability of adults with Down syndrome (DS). Twenty
      five adults with DS were separated into 2 groups. Fifteen subjects (mean age,
      24.5 years) constituted the experiment group, whereas 10 subjects (mean age, 24.7
      years) were in the control group of the study. Parameters measured were peak
      torque, isokinetic muscle endurance, and dynamic balance ability. All subjects
      performed a leg strength test on a Cyber II isokinetic dynamometer. In addition,
      the subjects' dynamic balance ability was measured by means of a balance deck
      (Lafayette). The experimental group followed a 12-week training program. As the
      results indicated, the experimental group showed a statistically significant
      improvement in all measured values when compared with the control group. It is
      concluded that adults with DS can improve their physical and kinetic abilities
      with the application of a systematic and well-designed training program.

PMID- 15142005
TI  - Comparison of caloric expenditure in intermittent and continuous walking bouts.
AB  - This study compared the caloric expenditure of 30 consecutive minutes (30 minute)
      of moderate intensity walking with 3 intermittent 10-minute bouts (3 x 10
      minutes) of moderate intensity walking in healthy, unfit men (40-49 years).
      Screening consisted of VO(2)max testing, which was measured using the Balke
      graded exercise test. Criteria for participation in this study included a
      measured VO(2)max less than 33.8 ml.kg(-1).min(-1) (<25th percentile for
      cardiorespiratory fitness). Twenty men participated in this study. Testing
      consisted of 4 trials with a minimum of 5 days between each trial. The 30-minute
      and 3 x 10-minute bouts were each performed twice to measure test-retest
      reliability. Once reliability was found, the 2 30-minute and the 2 3 x 10-minute
      trials were averaged for further data analyses; t-tests showed no significant
      differences in energy expenditure between 1 continuous 30-minute and the 3 x 10
      minute walking bouts at 274 and 279 kcal (p = 0.09), respectively. Thus, 3 x 10
      minute intermittent walking bouts throughout the day are equally beneficial, in
      terms of caloric expenditure, as 1 30-minute continuous walking bout.

PMID- 15142006
TI  - Physical fitness and job performance of firefighters.
AB  - Accurate correlations between a wide range of physical fitness measures and
      occupational demands are needed in order to identify specific fitness tests and
      training needs for firefighters. Twenty professional firefighters performed
      numerous fitness and job-related performance tests. Pearson product moment
      correlations were performed to identify the relationship between fitness
      components and job performance. Significant correlations (p <0.05) with job
      performance were identified for total fitness (r = -0.62), bench press strength
      (r = -0.66), hand grip strength (r = -0.71), bent-over row endurance (r = -0.61),
      bench press endurance (r = -0.73), shoulder press endurance (r = -0.71), bicep
      endurance (r = -0.69), squat endurance (r = -0.47), and 400-m sprint time (r =
      0.79). It is apparent that firefighting taxes virtually all aspects of physical
      fitness. These data can help the exercise specialist choose appropriate tests and
      prescribe specific fitness programs for firefighters. Traditional firefighter
      exercise programs focusing mainly on cardiovascular fitness should be replaced
      with physical conditioning programs that address all components of fitness.

PMID- 15142007
TI  - Physiologic profile of the fitness status of collegiate cheerleaders.
AB  - Cheerleading, traditionally considered a nonathletic activity, has evolved into a
      competitive sport requiring high levels of fitness. Despite the trend of
      cheerleaders performing increasingly difficult and athletic skills, very little
      is known about their fitness levels. The purpose of this study was to provide a
      physiological profile of the fitness status of a squad of collegiate
      cheerleaders. Eighteen cheerleaders (11 men and 7 women) participated in this
      study. Each subject completed a Bruce protocol maximal treadmill test, underwater
      weighing, 1 repetition maximum bench press, sit-and-reach test, push-ups, curl
      ups, and isokinetic strength testing. The mean and SD were calculated to provide
      the physical fitness profile for each parameter. A comparison to normative data
      demonstrated that cheerleaders have a high level of fitness and scores similar to
      other collegiate athletes.

PMID- 15142008
TI  - Effect of different training programs on the velocity of overarm throwing: a
      brief review.
AB  - Throwing velocity in overarm throwing is of major importance in sports like
      baseball, team handball, javelin, and water polo. The purpose of this literature
      review was to give an overview of the effect of different training programs on
      the throwing velocity in overarm throwing, provide a theoretical framework that
      explains findings, and give some practical applications based on these findings.
      The training studies were divided into 4 categories: (a) specific resistance
      training with an overload of velocity, (b) specific resistance training with an
      overload of force, (c) specific resistance training with a combination of
      overload of force and velocity, and (d) general resistance training according to
      the overload of force. Each category is presented and discussed.

PMID- 15142009
TI  - Ratings of perceived exertion and muscle activity during the bench press exercise
      in recreational and novice lifters.
AB  - This study examined ratings of perceived exertion (RPE) and electromyography
      (EMG) during resistance exercise in recreational and novice lifters. Fourteen
      novice (age = 21.5 +/- 1.5 years) and 14 recreationally trained (age = 21.9 +/-
      2.2 years) women volunteered to perform the bench press exercise at 60 and 80% of
      their 1 repetition maximum (1RM). RPE and EMG were measured during both
      intensities. Statistical analyses revealed that active muscle RPE increased as
      resistance exercise intensity increased from 60% 1RM to 80% 1RM (12.32 +/- 1.81
      vs. 15.14 +/- 1.74). Integrated EMG also increased as resistance exercise
      intensity increased from 60% 1RM to 80% 1RM (in the pectoralis major; 98.62 +/-
      17.54 vs. 127.98 +/- 29.02). No significant differences in RPE or EMG were found
      between novice and recreational lifters. These results indicate that RPE is
      related to the relative exercise intensity lifted as well as muscle activity
      during resistance exercise for both recreational and novice lifters. These
      results support the use of RPE as a method of resistance exercise intensity
      estimation for both types of lifters.

PMID- 15142010
TI  - Effects of different macronutrient consumption following a resistance-training
      session on fat and carbohydrate metabolism.
AB  - The effect of consuming meals of different macronutrient content on substrate
      oxidation following resistance exercise was examined in 9 resistance-trained men
      (26.2 +/- 2.4 years). Subjects completed 3 resistance exercise bouts of 8
      exercises and 1 warm-up set (50% of 10 repetition maximum [RM]), which were
      followed by 3 sets of 10 repetitions (72.7 +/- 1.9% 10RM), with 60 seconds of
      rest between sets. Forty-five minutes after exercise, subjects consumed meals of
      high fat (HF, 37% carbohydrate, 18% protein, and 45% fat), high carbohydrate (HC,
      79% carbohydrate, 20% protein, and 1% fat), or water (CON). Fat and carbohydrate
      oxidation were determined at 15-minute periods after meal consumption for 165
      minutes. Blood was collected at preexercise (pre), premeal (0 minutes), and 15,
      30, 45, 60, 90, 120, 150, and 180 minutes postmeal and was analyzed for insulin,
      glucose, triacylglycerols, and glycerol. There were no significant differences
      among the meal conditions for fat and carbohydrate oxidation. Insulin and glucose
      concentrations were significantly higher (p < 0.05) following HC at 15, 30, 45,
      60, and 90 minutes compared to HF and CON. Triacylglycerol concentrations were
      significantly higher (p < 0.05) following HF at 90, 120, 150, and 180 minutes
      compared to HC and CON. Fat and carbohydrate oxidation were not affected by
      differences in macronutrient meal consumption after an acute bout of resistance
      training. Different macronutrient consumption does influence insulin, glucose,
      and triacylglycerol concentrations after resistance exercise.

PMID- 15142011
TI  - Effect of grip strength and grip strengthening exercises on instantaneous bat
      velocity of collegiate baseball players.
AB  - Bat velocity is considered to be an important factor for successful hitting. The
      relationship between grip strength and bat velocity has not been conclusively
      established. The purposes of this study were to determine the relationship of
      grip strength to bat velocity and to ascertain whether the performance of
      resistance training exercises designed to specifically target the forearms and
      grip would significantly alter bat velocity. The subjects for this study were 23
      male members (mean +/- SD, age = 19.7 +/- 1.3 years, height = 182.5 +/- 5.9 cm,
      weight = 85.4 +/- 15.5 kg, experience = 14.4 +/- 1.7 years) of a varsity baseball
      team at a National Collegiate Athletic Association Division II school. The Jamar
      hand dynamometer was used to test grip strength, and the SETPRO Rookie was used
      to measure instantaneous bat velocity at the point of contact with the ball.
      Subjects were randomly divided into an experimental group and a control group.
      For 6 weeks, both groups participated in their usual baseball practice sessions,
      but the experimental group also performed extra forearm and grip strengthening
      exercises, whereas the control group did not. Pretest and posttest correlations
      between grip strength and bat velocity revealed no significant relationship
      between grip strength and bat velocity (pretest r = 0.054, p = 0.807; posttest r
      = 0.315, p = 0.145). A dependent t-test performed on all subjects revealed that a
      significant (p = 0.001) increase in bat velocity did occur over the course of the
      study. A covariate analysis, employing pretest bat velocity as the covariate,
      revealed no significant difference (p = 0.795) in posttest bat velocity scores
      between the experimental and control groups. Thus, increases in bat velocity
      occurred, but the differences were similar for both the experimental and control
      groups. The findings of this study suggest that grip strength and bat velocity
      are not significantly related, and that the allocation of time and energy for
      added training of the forearms in order to improve grip strength for the purpose
      of increasing bat velocity may not be warranted.

PMID- 15142012
TI  - Influence of type of mechanical loading, menstrual status, and training season on
      bone density in young women athletes.
AB  - Bone mineral density (BMD) variables were compared in 2 groups of women Division
      I collegiate athletes-gymnasts (GYM) and cross-country runners (CC)-during the
      preseason and during the competitive season. An osteogenic advantage may exist in
      women athletes involved in impact loading (gymnastics) over those women in active
      loading sports like long-distance running. The effects of menstrual status and
      the time of the training season on BMD also were examined. Dietary intake,
      menstrual status, BMD, and serum estradiol levels were measured during the
      preseason and during the competitive season in 26 women athletes (18-22 years of
      age). GYM had significantly higher BMD (p < 0.05) at all sites for both the pre-
      and posttests compared to CC. Neither group experienced a significant change (p >
      0.05) in BMD between trials for any site; however, CC showed slight decreases at
      all BMD sites from baseline to the posttest. GYM had a higher prevalence of self
      reported menstrual cycle disturbances than CC. No significant difference (p >
      0.05) in BMD was found between the eumenorrheic and menstrual dysfunction groups
      (oligo/amenorrheic). In conclusion, the gymnasts had significantly higher (p <
      0.05) BMD than the runners, suggesting BMD is influenced by the type of
      mechanical loading. Menstrual status did not significantly affect BMD in these
      women athletes. Cross-country runners were determined to be at greater risk than
      the gymnasts for low bone mass; thus, it is recommended that these athletes
      include more high-impact activities in their training regimen to optimize their
      bone health.

PMID- 15142013
TI  - Leukocytosis occurs in response to resistance exercise in men.
AB  - The purpose of this study was to determine the effects of a single bout of
      resistance exercise on immune cell numbers of moderately active men. Subjects
      were 16 male volunteers (mean +/- standard deviation [SD] age 30 +/- 7 years,
      height 180.1 +/- 7.0 cm, mass 83.97 +/- 10.33 kg); 8 were randomly assigned to
      treatment and 8 to control groups. Treatment was a common resistance training
      routine (3 sets of 8-10 repetitions at 75% of 1 repetition maximum) of 8 large
      muscle mass exercises using resistance machines. Blood samples were drawn before
      exercise and at 0 minutes (P0), 15 minutes (P15), and 30 minutes (P30)
      postexercise. Control subjects sat quietly in the training facility; blood was
      drawn at the same intervals as treatment. Leukocyte and lymphocyte (LY)
      subpopulation numbers were determined. Statistical analysis was analysis of
      variance (ANOVA) (repeated measures, p < or = 0.050) and multiple comparisons
      (Dunn method) to isolate variability. All leukocyte subpopulations, except
      basophils (BA) and eosinophils (EO), increased and counts declined by P15 and
      P30. Only neutrophils (NE) did not return to preexercise levels by P30. The
      majority of resistance exercise induced leukocytosis was due to an increase in
      circulating LY (natural killer cells increased most, CD4+/CD8+ ratio unchanged)
      and monocytes (MO). The transient, inconsequential immune cell population
      responses to resistance exercise are similar to those during aerobic activity.
      The lack of large alterations in and rapid recovery from cell number changes
      suggests that resistance exercise is not immunosuppressive.

PMID- 15142014
TI  - Self-selected resistance training intensity in novice weightlifters.
AB  - The purpose of this study was to determine the intensity of self-selected
      weightlifting exercise in untrained men and women. Thirteen men (age = 19.5 +/-
      1.9, height = 70.0 +/- 2.4 in., weight = 174 +/- 20.1 lb, % fat = 14.3 +/- 6.7)
      and 17 women (age =18.7 +/- 1.0, height = 64.9 +/- 2.3 in., weight = 135.4 +/-
      22.8 lb, % fat= 23.4 +/- 4.7) who were novice lifters completed seated bench
      press, leg extension, seated back row, military press, and biceps curl. Following
      self-selection trials, subjects' 1 repetition maximum (1RM) was assessed for each
      lift. Results showed that for both genders, self-selected loads were all below
      60% 1RM. All lift intensities were similar for men and women (range = 42-57%
      1RM). Repetitions completed and rating of perceived exertion responses were not
      different between gender. Results show that subjects do not select a lifting
      intensity sufficient to induce hypertrophic responses and subsequent strength
      increases.

PMID- 15142015
TI  - Physiological and sport-specific skill response of olympic youth soccer athletes.
AB  - Although many studies have been focused on soccer athletes, no comprehensive
      studies have been conducted on adolescent soccer athletes in the United States.
      Therefore, the purpose of this study was to quantify the physiological and sport
      specific skill characteristics of Olympic Developmental Program (ODP) soccer
      athletes by age group and game experience. Following written, informed consent,
      59 male athletes (age = 14.6 +/- 2.0 years; wt = 60.5 +/- 1.4 kg; ht = 172.4 +/-
      1.2 cm) completed a battery of tests to determine aerobic power (VO(2)max), heart
      rate (HR(max)), ventilation (VE(max)), respiratory exchange ratio (RER),
      anaerobic threshold (AT), blood pressure (BP(rest/max)), anaerobic power/capacity
      [peak power (PP), mean power (MP), total work output (TWO), fatigue index (FI)],
      leg power [vertical squat jump (VJS), countermovement jump (VJC)], body
      composition [percent body fat (%BF), lean body mass (LBM)], joint range of motion
      (trunk, back, hip, knee, and ankle), and agility/sport-specific skills (T-test,
      line drill test, juggling test, Johnson wall volley, and modified-Zelenka
      circuit). Factor analyses with subsequent multivariate analyses of variance
      (MANOVAs) indicated significant main effects across age (p = 0.0001) but not by
      game experience (p = 0.82). Older athletes exhibited greater height, weight, LBM,
      VE(max), Time(max), PP, TWO, and VSJ values than younger athletes. Although not
      significant, there were differences with increasing age in the agility tests (T
      test, wall volley, and juggling test). In conclusion, improvements in anaerobic
      power, agility, and sport-specific skill should be addressed at this
      developmental level of competition.

PMID- 15142016
TI  - Sports performance graduate program interest and need survey: a brief report from
      the NSCA Education Committee.
AB  - The Education Recognition Program (ERP) was developed to acknowledge academic
      institutions meeting departmental criteria established by the National Strength
      and Conditioning Association (NSCA) for having an area of concentration in
      undergraduate strength and conditioning. Since its inception, over 40
      universities have received recognition status. The NSCA is currently examining
      the interest, need, and feasibility of creating an ERP for graduate curriculum
      specific to sports performance. The current investigation included a survey of
      Division I, II, and III strength and conditioning professionals. Surveys were
      mailed to 215 coaches, of which 53 responded (26% rate of return). Five factors
      were extracted from the questionnaire and were subsequently named: Application of
      Science to Strength and Conditioning, Professional Development, Graduate
      Curriculum Support, Graduate Program Requirements, and Graduate Assistantships. A
      one-way analysis of variance (ANOVA) found significant differences on Application
      of Science to Strength and Conditioning and Professional Development when
      comparing highest degree earned. Pairwise analysis indicated that individuals
      with Master's degrees scored those factors higher compared with individuals with
      Bachelor's degrees. The results from this survey provide initial information from
      current strength and conditioning professionals regarding the interest and need
      for developing formalized graduate curriculum specifically for sports
      performance.

PMID- 15142018
TI  - Characteristics of elite open-water swimmers.
AB  - Open-water swimming (5, 10, and 25 km) has many unique challenges that separate
      it from other endurance sports, like marathon running and cycling. The
      characteristics of a successful open-water swimmer are unclear. The purpose of
      this study was to determine the physical and metabolic characteristics of a group
      of elite-level open-water swimmers. The open-water swimmers were participating in
      a 1-week training camp. Anthropometric, metabolic, and blood chemistry
      assessments were performed on the athletes. The swimmers had a VO(2)peak of 5.51
      +/- 0.96 and 5.06 +/- 0.57 ml.kg(-1).min(-1) for males and females, respectively.
      Their lactate threshold (LT) occurred at a pace equal to 88.75% of peak pace for
      males and 93.75% for females. These elite open-water swimmers were smaller and
      lighter than competitive pool swimmers. They possess aerobic metabolic
      alterations that resulted in enhanced performance in distance swimming. Trainers
      and coaches should develop dry-land programs that will improve the athlete's
      muscular endurance. Furthermore, programs should be designed to increase the LT
      velocity as a percentage of peak swimming velocity.

PMID- 15142017
TI  - Short-term low-carbohydrate diet dissociates lactate and ammonia thresholds in
      men.
AB  - A low-carbohydrate (L-CHO) diet has been shown to shift the lactate threshold
      toward higher workloads. The aim of the present study was to examine the effect
      of an L-CHO diet on the ammonia threshold and to compare it with the lactate
      threshold in men. The plasma catecholamine threshold was also measured. Eight
      young, untrained men participated in the study. Two exercise tests with graded
      workload were performed. The workload was increased every 3 minutes by 40 W until
      volitional exhaustion. The first test was performed after 3 days of a controlled
      mixed diet. After the first test, the mixed diet was switched to a L-CHO diet.
      Three days later the same test was repeated. The blood concentration of lactate,
      ammonia, noradrenaline, and adrenaline was measured before and after each
      workload in both groups. It was found that the concentration of the examined
      compounds in the blood increases exponentially with graded workload after each
      kind of diet. This led us to calculate the blood ammonia, lactate, epinephrine,
      and norepinephrine thresholds. The thresholds were defined as points at which the
      concentration of a given compound starts to increase in a nonlinear fashion,
      which is calculated using 2 segmental linear regressions. After the mixed diet,
      the threshold for each compound occurs at the same workload. The L-CHO diet
      resulted in dissociation of the lactate threshold from the ammonia threshold: the
      lactate threshold was shifted toward a higher workload, whereas the ammonia
      threshold was shifted toward a lower workload. The norepinephrine threshold was
      also shifted toward a lower workload, and the epinephrine threshold remained
      unchanged. The results obtained indicate that an L-CHO diet accelerates
      production of ammonia and delays production of lactate during graded exercise, as
      well as that diet must be strictly controlled when ammonia and lactate thresholds
      are measured.

PMID- 15142019
TI  - Musculoskeletal adaptations to 16 weeks of eccentric progressive resistance
      training in young women.
AB  - We investigated the musculoskeletal adaptations and efficacy of a whole-body
      eccentric progressive resistance-training (PRT) protocol in young women. Subjects
      (n = 37; mean age, 24.3) were randomly assigned to one of 3 groups: high
      intensity eccentric PRT (HRT), low-intensity eccentric PRT (LRT), or control.
      Subjects performed 3 sets of 6 repetitions at 125% intensity or 3 sets of 10
      repetitions at 75% intensity in the HRT and LRT groups, respectively, 2 times per
      week for 16 weeks. Strength was determined by the concentric 1-repetition maximum
      (1RM) standard. Bone mass and body composition were measured by dual-energy x-ray
      absorptiometry (DXA). Blood and urine samples were obtained for
      deoxypyridinoline, osteocalcin, creatine kinase, and creatinine. Data were
      analyzed by repeated-measures analysis of variance with post hoc comparisons.
      Strength increased 20-40% in both training groups. Lean body mass increased in
      the LRT (0.7 +/- 0.6 kg) and HRT (0.9 +/- 0.9 kg) groups. Bone mineral content
      increased (0.855 +/- 0.958 g) in the LRT group only. Deoxypyridinoline decreased
      and osteocalcin increased in the HRT and LRT groups, respectively. These findings
      suggest that submaximal eccentric training is optimal for musculoskeletal
      adaptations and that the intensity of eccentric training influences the early
      patterns of bone adaptation.

PMID- 15142020
TI  - Influence of surface on muscle damage and soreness induced by consecutive drop
      jumps.
AB  - This study compared the magnitude of muscle damage induced when consecutive drop
      jumps (DJs) were performed on sand vs. firm (wood) surfaces from a height of 0.6
      m. Eight subjects performed DJs on a sand surface at a depth of 0.2 m (S
      condition), and 8 other subjects performed DJs on a wood surface (F condition).
      Each set consisted of 20 DJs with an interval of 10 seconds between jumps.
      Subjects performed 5 sets of DJs with 2 minutes between sets. Maximal isometric
      force, muscle soreness, and plasma creatine kinase (CK) activity were measured
      immediately before and immediately after the DJ exercise as well as 1, 24, 48,
      72, and 96 hours after the DJ exercise. All measures changed significantly (p <
      0.05) after exercise for both conditions; however, significantly (p < 0.05)
      smaller changes in these measures were evident for the S condition than for the F
      condition. These results show that DJs on a sand surface induce less muscle
      damage than on a firm surface. Training on sand may improve aerobic capacity or
      strength with a low risk of muscle damage.

PMID- 15142021
TI  - Acute effects of static stretching on peak torque in women.
AB  - The purpose of this study was to examine the effects of static stretching on
      concentric, isokinetic leg extension peak torque (PT) at 60 and 240 degrees.s(-1)
      in the stretched and unstretched limbs. The PT of the dominant (stretched) and
      nondominant (unstretched) leg extensors were measured on a calibrated Cybex 6000
      dynamometer. Following the prestretching PT assessments, the dominant leg
      extensors were stretched using 1 active and 3 passive stretching exercises. After
      the stretching, PT was reassessed. The results of the statistical analyses
      indicated that PT decreased following the static stretching in both limbs and at
      both velocities (60 and 240 degrees.s(-1)). The present findings suggested that
      the stretching-induced decreases in PT may be related to changes in the
      mechanical properties of the muscle, such as an altered length-tension
      relationship, or a central nervous system inhibitory mechanism. Overall, these
      findings, in conjunction with previous studies, indicated that static stretching
      impairs maximal force production. Strength and conditioning professionals should
      consider this before incorporating static stretching in preperformance
      activities. Future studies are needed to identify the underlying mechanisms that
      influence the time course of stretching-induced decreases in maximal force
      production for athletes and nonathletes across the age span.

PMID- 15142022
TI  - Training vs. body image: does training improve subjective appearance ratings?
AB  - The purpose of this study was to determine if a short-term exercise program (6
      weeks) could improve subjective physical appearance ratings. Twenty-five
      previously sedentary adult men (aged 18-40 years) were randomly assigned to one
      of 3 training groups: cardiovascular, strength, or control. Subjects
      participating in an exercise group trained for an average of 34 minutes, 3 times
      per week. All subjects were pre- and posttested to determine body composition,
      strength, and cardiovascular fitness. Subjects were also digitally photographed
      from 4 angles. The photographs were rated by the subjects and by a panel of 6
      judges using an analog scale. There was no significant difference in the groups
      by trials interaction effect for pre- and post-Vo(2)max, percent fat, total lean
      tissue, percent limb fat, percent trunk fat, lean trunk tissue, or lean limb
      tissue. The subjects rated themselves higher than the panel, with average scores
      of 4.74 vs. 3.46, 4.26 vs. 3.10, and 4.61 vs. 3.49 for the cardiovascular,
      strength, and control groups, respectively (p < 0.05). The men of the panel rated
      the subjects significantly higher than did the women, with average scores of 4.61
      vs. 2.31, 4.13 vs. 2.06, and 4.53 vs. 2.18 for the cardiovascular, resistance,
      and control groups, respectively (p < 0.05). This study showed that a 6-week
      training program did not change self-rated or panel-rated appearance scores.

PMID- 15142023
TI  - Creatine serum is not as effective as creatine powder for improving cycle sprint
      performance in competitive male team-sport athletes.
AB  - This study examined the effects of supplementation with either creatine
      monohydrate powder in solution (CP) or a widely available creatine serum (CS) on
      performance in a repeated maximal sprint cycling test (10 x 6 seconds, 24-second
      passive rest between sprints). Using a randomized, double-blind, crossover
      design, 11 competitive male athletes supplemented with creatine in 2 forms
      according to the manufacturer's recommendations on 2 separate occasions. The 2
      supplementation protocols were (a) 20 g.day(-1) x 6 days of creatine powder in
      solution plus a placebo serum (CP) or (b) 5 ml.day(-1) x 6 days of creatine serum
      plus a placebo powder (CS). Subjects completed 2 familiarization trials before
      the 6-day supplementation period. A repeated maximal sprint cycling test was
      performed prior to and immediately postsupplementation. A 7-week washout period
      separated the 2 supplementation protocols. Subjects' total work (9.6%) and peak
      power (3.4%) in the cycle sprint improved significantly (p < 0.05) after loading
      with CP, but there was little change after loading with CS. The present data
      support previous research findings showing an ergogenic effect of CP
      supplementation but indicate that supplementation with CS does not affect sprint
      cycling performance. Although the levels of creatine in each formulation were not
      determined, a substantial conversion of creatine into creatinine has been
      reported in many formulations and may explain the present findings.

PMID- 15142024
TI  - Coaching difference: a case study of 4 African American women student-athletes.
AB  - The purpose of the present investigation was to describe the experiences of
      African American women student-athletes and the role that coaches play in those
      experiences. This study profiles 4 women who participated in National Collegiate
      Athletic Association Division I cross-country, crew, track and field, and
      volleyball. Using data gathered through the qualitative methods of document
      analysis, background questionnaires, focus groups, grounded surveys, and in-depth
      individual interviews, the results of the study are focused on how coaches affect
      individual student-athletes and, most specifically, a particular segment of the
      athletic world that tends to be overlooked: the African American woman. Results
      are organized according to the following themes that emerged through the
      collection of data: (a) the involvement of coaches in African American women
      student-athletes' exposure to racism through stereotypes, (b) coaches as
      significant influences on African American women becoming involved and remaining
      involved in sport, and (c) power structures in sport and society affecting
      African American women as a form of institutional racism. A practical
      applications section follows the results.

PMID- 15142025
TI  - Acute effects of heavy preloading on vertical and horizontal jump performance.
AB  - The purpose of this study was to investigate the acute effects of a heavy dynamic
      preload, consisting of 1 set of 5 repetition maximum (5RM) back squats, on
      countermovement vertical jump (VJ) and horizontal jump (HJ) performance. The
      study also investigated the ability of subjects to learn to apply the effects of
      the preload over subsequent training sessions. Nineteen (N = 19) resistance
      trained men (age = 25.0 +/- 4.8 years; weight = 79.3 +/- 6.6 kg) participated in
      the study. Each subject took part in 4 practice and 4 testing sessions. The 4
      practice sessions were included to allow for any learning effects of VJ and HJ to
      stabilize and to establish a true 5RM back squat. The 4 testing sessions were
      included to see if subjects were able to capitalize on the repeat exposure to the
      protocol. One practice session consisted of a 10-minute warm-up (5 minutes of
      cycling and 5 minutes of stretching), 2 sets of VJ and HJ (each set of VJ and HJ
      consisted of 4 jump repetitions) with a 5-minute rest between sets, progressive
      5RM back squat evaluation, and 2 final sets of VJ and HJ. Both VJ and HJ
      increased approximately 2% over the 4 practice sessions, and 5RM back squat
      strength improved from 164.2 +/- 25.1 kg to 196.9 +/- 23.0 kg (p < or = 0.05).
      The 4 testing sessions each consisted of the standardized warm-up, 1 set of 4 VJs
      and HJs, a 5-minute rest, 5RM back squat, a 5-minute rest, and the final set of
      VJs and HJs. Pre- and post-5RM VJ and HJ order was randomly assigned. The results
      indicated no significant differences occurred between the mean or maximal values
      for either VJ or HJ as a consequence of the dynamic preload exercise. In
      addition, the results reflected an inability of subjects to benefit from the
      repeated exposure to the heavy dynamic preload exercise protocol.

PMID- 15142026
TI  - Monitoring exercise intensity during resistance training using the session RPE
      scale.
AB  - This study investigated the reliability of the session rating of perceived
      exertion (RPE) scale to quantify exercise intensity during high-intensity (H),
      moderate-intensity (M), and low-intensity (L) resistance training. Nine men (24.7
      +/- 3.8 years) and 10 women (22.1 +/- 2.6 years) performed each intensity twice.
      Each protocol consisted of 5 exercises: back squat, bench press, overhead press,
      biceps curl, and triceps pushdown. The H consisted of 1 set of 4-5 repetitions at
      90% of the subject's 1 repetition maximum (1RM). The M consisted of 1 set of 10
      repetitions at 70% 1RM, and the L consisted of 1 set of 15 repetitions at 50%
      1RM. RPE was measured following the completion of each set and 30 minutes
      postexercise (session RPE). Session RPE was higher for the H than M and L
      exercise bouts (p < or = 0.05). Performing fewer repetitions at a higher
      intensity was perceived to be more difficult than performing more repetitions at
      a lower intensity. The intraclass correlation coefficient for the session RPE was
      0.88. The session RPE is a reliable method to quantify various intensities of
      resistance training.

PMID- 15142028
TI  - Influence of familiarization on the reliability of vertical jump and acceleration
      sprinting performance in physically active men.
AB  - The purpose of the present study was to determine the number of familiarization
      sessions required to obtain an accurate measure of reliability associated with
      loaded vertical jump and 20-m sprint running performance. Ten physically active
      men attended 5 separate testing sessions over a 3-week period where they
      performed unloaded and loaded (10-kg extra load) countermovement (CMJ) and static
      (SJ) jumps, followed by straight-line 20-m sprints. Jump height was recorded for
      the vertical jumps using a jump mat, while the time for 10 m and 20 m was
      recorded during the sprints using photocells. The highest (jump conditions) and
      fastest (sprint) of 3 trials performed during each of the 5 testing sessions was
      used in the subsequent analysis. Familiarization was assessed using the scores
      obtained during the 5 separate testing sessions. Reliability was assessed by
      calculating intraclass correlation coefficients (ICCs) and coefficient of
      variation (CV). No significant differences were obtained between the testing
      sessions for any of the measures. ICCs ranged from 0.89 to 0.95, while CVs ranged
      from 1.9 to 2.6%. These results indicate that high levels of reliability can be
      achieved without the need for familiarization sessions when using loaded and
      unloaded CMJ and SJ and 20-m sprint performance with physically active men.

PMID- 15142027
TI  - Comparison of selected physical fitness and performance variables between NCAA
      Division I and II football players.
AB  - The purpose of this study was to compare selected physical fitness and
      performance variables between National Collegiate Athletic Association (NCAA)
      Division I and II football players. The subjects included offensive and defensive
      starters, excluding kickers and punters from 26 NCAA Division I and 23 Division
      II teams. Offensive players were grouped and compared by the following positions:
      quarterback, running back, wide receiver, tight end, and line. Defensive players
      were grouped and compared by the following positions: line, linebackers, and
      backs. Division I players were better in 58 of 117 comparisons (p < or = 0.01).
      Division II players were not found to be better in any of the variables studied.

PMID- 15142029
TI  - Mg2+-creatine chelate and a low-dose creatine supplementation regimen improve
      exercise performance.
AB  - We tested the hypotheses that, compared with a placebo group or creatine (Cr)
      group, a Mg(2+)-Cr chelate group would demonstrate improvements in the 1
      repetition maximum (1RM) on the bench press and be able to perform more work at
      70% of the 1RM for the bench press. Thirty-one weight-trained men were randomly
      assigned in a double-blind manner to a placebo group (multidextran), a Cr group
      (2.5 g of Cr daily), or a Mg(2+)-Cr group (2.5 g of Cr daily). Baseline data were
      collected for the bench press 1RM and maximal work completed during a fatigue set
      at 70% of the 1RM. Following 10 days of Cr supplementation, follow-up tests were
      completed for the dependent variables. Groups were similar when the change in 1RM
      was evaluated either absolutely or relatively. Both the Cr and the Mg(2+)-Cr
      groups had significantly larger increases in work, both absolutely and
      relatively, when compared with the placebo group. Partial support for the
      hypothesis suggests that low doses of Cr are effective at increasing fiber Cr
      content, and consequently, performance. Further, the Cr and Mg(2+)-Cr groups were
      similar in both performance tests, suggesting that the proposed mechanism of
      entry is no better than the conventional method when 2.5 g of Cr is administered
      and performance is measured as work. This study raises the possibility that a low
      dose of Cr may be an effective means of enhancing performance after short-term
      ingestion.

PMID- 15142030
TI  - Effects of carbohydrate refeeding on physiological responses and psychological
      and physical performance following acute weight reduction in collegiate
      wrestlers.
AB  - The purpose of this study was to determine the effects of carbohydrate refeeding
      on intermittent sprint exercise, blood lactate response, and mood following a
      typical weight-reduction program practiced by college wrestlers. Fifteen
      collegiate wrestlers from the University of Northern Iowa completed 3 trials of
      intermittent arm cranking and a mood inventory prior to weigh-ins (baseline),
      after weigh-ins, and 1 hour postconsumption of either 1.5 g carbohydrate (CHO)/kg
      body mass carbohydrate beverage (25% solution) or placebo taken within 1 hour
      after weigh-ins. Blood lactate responses were determined with each trial.
      Repeated measures analysis of variance indicated no significant interaction
      between group and trial for total work (p = 0.08), blood lactate (p = 0.29),
      positive mood (p = 0.49), or negative mood (p = 0.78). Simple effects analysis
      indicated a significant difference in lactate response between trials (p =
      0.002); however, no difference for work (p = 0.75), positive mood (p = 0.13), or
      negative mood (p = 0.08). The results of this study suggest that intermittent
      sprint exercise, blood lactate response, and mood were not positively affected by
      ingestion of CHOs following an acute weight-reduction period.

PMID- 15142031
TI  - Regulation of transcription by Saccharomyces cerevisiae 14-3-3 proteins.
AB  - 14-3-3 proteins form a family of highly conserved eukaryotic proteins involved in
      a wide variety of cellular processes, including signalling, apoptosis, cell-cycle
      control and transcriptional regulation. More than 150 binding partners have been
      found for these proteins. The yeast Saccharomyces cerevisiae has two genes
      encoding 14-3-3 proteins, BMH1 and BMH2. A bmh1 bmh2 double mutant is unviable in
      most laboratory strains. Previously, we constructed a temperature-sensitive bmh2
      mutant and showed that mutations in RTG3 and SIN4, both encoding transcriptional
      regulators, can suppress the temperature-sensitive phenotype of this mutant,
      suggesting an inhibitory role of the 14-3-3 proteins in Rtg3-dependent
      transcription [van Heusden and Steensma (2001) Yeast 18, 1479-1491]. In the
      present paper, we report a genome-wide transcription analysis of a temperature
      sensitive bmh2 mutant. Steady-state mRNA levels of 60 open reading frames were
      increased more than 2.0-fold in the bmh2 mutant, whereas those of 78 open reading
      frames were decreased more than 2.0-fold. In agreement with our genetic
      experiments, six genes known to be regulated by Rtg3 showed elevated mRNA levels
      in the mutant. In addition, several genes with other cellular functions,
      including those involved in gluconeogenesis, ergosterol biosynthesis and stress
      response, had altered mRNA levels in the mutant. Our data show that the yeast 14
      3-3 proteins negatively regulate Rtg3-dependent transcription, stimulate the
      transcription of genes involved in ergosterol metabolism and in stress response
      and are involved in transcription regulation of multiple other genes.

PMID- 15142032
TI  - Characterization of a UDP-N-acetyl-D-galactosamine:polypeptide N
      acetylgalactosaminyltransferase with an unusual lectin domain from the
      platyhelminth parasite Echinococcus granulosus.
AB  - As part of a general project aimed at elucidating the initiation of mucin-type O
      glycosylation in helminth parasites, we have characterized a novel ppGalNAc-T
      (UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase) from
      the cestode Echinococcus granulosus (Eg-ppGalNAc-T1). A full-length cDNA was
      isolated from a library of the tissue-dwelling larval stage of the parasite, and
      found to code for a 654-amino-acid protein containing all the structural features
      of ppGalNAc-Ts. Functional characterization of a recombinant protein lacking the
      transmembrane domain showed maximal activity at 28 degrees C, in the range 6.5
      7.5 pH units and in the presence of Cu2+. In addition, it transferred GalNAc to a
      broad range of substrate peptides, derived from human mucins and O-glycosylated
      parasite proteins, including acceptors containing only serine or only threonine
      residues. Interestingly, the C-terminal region of Eg-ppGalNAc-T1 bears a highly
      unusual lectin domain, considerably longer than the one from other members of the
      family, and including only one of the three ricin B repeats generally present in
      ppGalNAc-Ts. Furthermore, a search for conserved domains within the protein C
      terminus identified a fragment showing similarity to a recently defined domain,
      specialized in the binding of organic phosphates (CYTH). The role of the lectin
      domain in the determination of the substrate specificity of these enzymes
      suggests that Eg-ppGalNAc-T1 would be involved in the glycosylation of a special
      type of substrate. Analysis of the tissue distribution by in situ hybridization
      and immunohistochemistry revealed that this transferase is expressed in the
      hydatid cyst wall and the subtegumental region of larval worms. Therefore it
      could participate in the biosynthesis of O-glycosylated parasite proteins exposed
      at the interface between E. granulosus and its hosts.

PMID- 15142034
TI  - Thermostable beta-cyclodextrin conjugates of two similar plant amine oxidases and
      their properties.
AB  - Syntheses of conjugates of garden pea (Pisum sativum) and grass pea (Lathyrus
      sativus) amine oxidases (PSAO and GPAO respectively) with BCD (beta
      cyclodextrin), performed to improve the thermostability of the enzymes, are
      described in the present study. Periodate-oxidized BCD reacted with the enzyme
      proteins via free primary amino groups in a buffered solution containing
      cyanoborohydride as a reductant. Although the specific activities of PSAO and
      GPAO partially decreased after modification, Km values determined for the best
      diamine substrates remained almost unchanged. Both the BCD conjugates could be
      incubated at 65 degrees C for 30 min without considerable inactivation, and the
      residual activity remained detectable even after incubation at 75 degrees C. The
      conjugates contained approx. 30% of neutral sugars. Molecular masses of BCD-PSAO
      and BCD-GPAO (180 kDa), as estimated by gel-permeation chromatography, were
      higher compared with the value of 145 kDa for the native enzymes. This was in
      good correlation with the number of modified lysine residues determined by a
      spectrophotometric method. Peptide mass fingerprints of tryptic digests of BCD
      PSAO and BCD-GPAO were less specific than those of the native enzymes when
      compared with the database sequence of PSAO. As a consequence of the
      modification, many unidentified peaks were observed in the digests of the studied
      conjugates that were not seen in the digests of native PSAO and GPAO. Only some
      of these peaks overlapped between BCD-PSAO and BCD-GPAO. The BCD conjugates
      described in the present study represent suitable candidates for biotechnological
      applications, e.g. in analyses using biosensors, which might benefit from
      increased storage stability and amine oxidation at high temperatures.

PMID- 15142035
TI  - Atrial natriuretic peptide levels in adult patients before and after surgery for
      correction of atrial septal defects: relationship with atrial arrhythmias.
AB  - In the present study, we have examined whether increased N-ANP (N-terminal pro
      ANP) levels before and after surgery in patients with ASD (atrial septal defect)
      along with echocardiographic findings provide a better insight into the
      pathophysiology and increased morbidity and mortality following corrective
      surgery. Eighteen adult ASD patients (> 20 years of age; six male and 12 female)
      with shunts (Qp/Qs > or = 2, where Qp/Qs is the pulmonary blood flow/systemic
      blood flow) had complete echocardiographic, clinical and laboratory parameters
      evaluated before and 6 months after surgery. Eight age- and sex-matched
      individuals (three male and five female) were enrolled as a control group. Blood
      samples for N-ANP analysis were obtained in both groups. N-ANP levels in the
      peripheral blood sample from ASD patients before surgery were significantly
      higher than those in the control group. In patients with ASD, mean N-ANP levels
      obtained from the pulmonary artery were significantly higher than that obtained
      from the peripheral vein. RA (right atrial) area, adjusted for body surface area,
      and RA long-axis and short-axis measurements were significantly higher in the
      patient group than the control group. N-ANP was correlated significantly with
      these parameters. Following corrective surgery, N-ANP values and RA area, RA long
      axis and short-axis normalization decreased significantly and were accompanied by
      a decrease in systolic mean pulmonary artery pressure. N-ANP levels were
      normalized following septal closure in most patients, except in those with atrial
      fibrillation attacks following corrective surgery. In conclusion, we have shown
      correlations among variables indicating changes in the architecture of the right
      atrium along with temporal changes in ANP providing insights into the
      pathophysiology of post-operative atrial arrhythmias.

PMID- 15142033
TI  - Expression of taurine transporter is regulated through the TonE (tonicity
      responsive element)/TonEBP (TonE-binding protein) pathway and contributes to
      cytoprotection in HepG2 cells.
AB  - In hypertonic environment, taurine accumulates in cells via activation of TauT
      (taurine transporter) as an adaptive regulation. Recent studies revealed that
      TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway
      regulated the expression of various molecules which protect cells against
      hypertonic stress. In the present study, we investigated the osmoregulatory
      mechanisms of TauT expression. TauT was up-regulated at both functional and
      transcriptional levels in HepG2 under hypertonic condition. The TonE site was
      identified in the promoter region of TauT gene. Reporter gene assay revealed that
      promoter activity was increased under hypertonic conditions, whereas deletion or
      mutation of TonE sequence abolished the induction of the promoter activity in
      response to hypertonicity. By using the reporter gene plasmids containing a TonE
      site of TauT promoter (p2xTonE-Luc), it was demonstrated that a TonE site was
      sufficient for the hypertonicity-mediated activation of TauT promoter.
      Importantly, co-transfection of TauT promoter gene plasmid with wild-type TonEBP
      expression vector enhanced promoter activity under isotonic conditions, whereas
      dominant-negative TonEBP abrogated the TauT promoter activity induced by
      hypertonicity. Finally, treatment with taurine prevented HepG2 cells from cell
      death induced by hypertonic medium. These findings suggested that induction of
      TauT by hypertonicity is mediated by the activation of the TonE/TonEBP pathway
      and confers resistance to hypertonic stress.

PMID- 15142036
TI  - The pre-mRNA-splicing factor SF3a66 functions as a microtubule-binding and 
      bundling protein.
AB  - SF3a (splicing factor 3a) complex is an essential component of U2 snRNPs (small
      nuclear ribonucleoprotein particles), which are involved in pre-mRNA splicing.
      This complex consists of three subunits: SF3a60, SF3a66 and SF3a120. Here, we
      report a possible non-canonical function of a well-characterized RNA-splicing
      factor, SF3a66. Ectopic expression experiments using each SF3a subunit in N1E 115
      neuroblastoma cells reveals that SF3a66 alone can induce neurite extension,
      suggesting that SF3a66 functions in the regulation of cell morphology. A screen
      for proteins that bind to SF3a66 clarifies that SF3a66 binds to beta-tubulin, and
      also to microtubules, with high affinity, indicating that SF3a66 is a novel MAP
      (microtubule-associated protein). Electron microscopy experiments show that
      SF3a66 can bundle microtubules, and that bundling of microtubules is due to cross
      bridging of microtubules by high-molecular-mass complexes of oligomerized SF3a66.
      These results indicate that SF3a66 is likely to be a novel MAP, and can function
      as a microtubule-bundling protein independently of RNA splicing.

PMID- 15142037
TI  - Free aminothiols, glutathione redox state and protein mixed disulphides in aging
      Drosophila melanogaster.
AB  - The main purpose of the present study was to test the hypothesis that the aging
      process is associated with a pro-oxidizing shift in the cellular redox state. The
      amounts of the redox-sensitive free aminothiols (glutathione, cysteine, Cys-Gly
      and methionine) and protein mixed disulphides were measured at different ages and
      ambient temperatures in Drosophila melanogaster. GSH/GSSG ratios decreased
      significantly with increasing age of the flies, due to an increase in GSSG
      content. Concentrations of Cys-Gly increased and methionine decreased with age.
      The amounts of protein mixed disulphides, measured as protein-cysteinyl, protein
      Cys-Gly and protein-glutathionyl mixed disulphides, increased as a function of
      age. The pattern of changes in free aminothiol content, glutathione-redox state
      and protein mixed disulphides varied in proportion to the ambient temperature,
      which is inversely related to the life expectancy of the flies. Collectively,
      these results support the idea that the pro-oxidizing shift in the glutathione
      redox state, the decrease in methionine content and increase in abundance of
      protein mixed disulphides are associated with the life expectancy of flies, and
      are indicative of enhanced oxidative stress during aging.

PMID- 15142039
TI  - Quantitative description of the interaction between folate and the folate-binding
      protein from cow's milk.
AB  - A detailed study has been carried out on the dependence of folate binding on the
      concentration of FBP (folate-binding protein) at pH 5.0, conditions selected to
      prevent complications arising from the pre-existing self-association of the
      acceptor. In contrast with the mandatory requirement that reversible interaction
      of ligand with a single acceptor site should exhibit a unique, rectangular
      hyperbolic binding curve, results obtained by ultrafiltration for the FBP-folate
      system required description in terms of (i) a sigmoidal relationship between
      concentrations of bound and free folate and (ii) an inverse dependence of
      affinity on FBP concentration. These findings have been attributed to the
      difficulties in determining the free ligand concentration in the FBP-folate
      mixtures for which reaction is essentially stoichiometric. This explanation also
      accounts for the similar published behaviour of the FBP-folate system at neutral
      pH, which had been attributed erroneously to acceptor self-association, a
      phenomenon incompatible with the experimental findings because of its prediction
      of a greater affinity for folate with increasing FBP concentration.

PMID- 15142038
TI  - Gene- and cell-type-specific effects of signal transduction cascades on metal
      regulated gene transcription appear to be independent of changes in the
      phosphorylation of metal-response-element-binding transcription factor-1.
AB  - Post-translational modification of MTF-1 (metal-response-element-binding
      transcription factor-1) was suggested to play a role in its metalloregulatory
      functions. In the present study, pulse labelling and two-dimensional
      electrophoresis-Western blotting were used to demonstrate that, although MTF-1 is
      highly modified in vivo, its phosphorylation level does not rapidly change in
      response to metals, nor does its overall modification pattern. Recombinant MTF-1
      was found to serve as an in vitro substrate for casein kinase II, c-Jun N
      terminal kinase and protein kinase C, but inhibition of these kinases in vivo did
      not significantly change the modification pattern of MTF-1. Northern blotting
      revealed that inhibitors of casein kinase II and c-Jun N-terminal kinase severely
      attenuate the metal-induced transcription of the native chromatin-packaged
      metallothionein-I and zinc transporter-1 genes, whereas protein kinase C
      inhibitors exerted gene- and cell-type-specific effects on the metal regulation
      and basal expression of these two genes. A chromatin immunoprecipitation assay
      was used to demonstrate that none of these inhibitors prevent the metal-dependent
      recruitment of MTF-1 to the MT-I promoter. In brief, results of the present study
      suggest that protein kinases may not alter the phosphorylation state of MTF-1
      during the rapid-response phase to metals, nor do they regulate the metal
      dependent formation of a stable MTF-1-chromatin complex. Instead, protein kinases
      may exert their interdependent effects on metal-induced gene expression by acting
      on cofactors that interact with MTF-1.

PMID- 15142040
TI  - Metal-binding mechanism of Cox17, a copper chaperone for cytochrome c oxidase.
AB  - Cox17, a copper chaperone for cytochrome c oxidase, is an essential and highly
      conserved protein. The structure and mechanism of functioning of Cox17 are
      unknown, and even its metalbinding stoichiometry is elusive. In the present
      study, we demonstrate, using electrospray ionization-MS, that porcine Cox17 binds
      co-operatively four Cu+ ions. Cu4Cox17 is stable at pH values above 3 and
      fluorescence spectra indicate the presence of a solvent-shielded multinuclear
      Cu(I) cluster. Combining our results with earlier EXAFS results on yeast CuCox17,
      we suggest that Cu4Cox17 contains a Cu4S6-type cluster. At supramillimolar
      concentrations, dithiothreitol extracts metals from Cu4Cox17, and an apparent
      copper dissociation constant KCu=13 fM was calculated from these results. Charge
      state distributions of different Cox17 forms suggest that binding of the first
      Cu+ ion to Cox17 causes a conformational change from an open to a compact state,
      which may be the rate-limiting step in the formation of Cu4Cox17. Cox17 binds non
      co-operatively two Zn2+ ions, but does not bind Ag+ ions, which highlights its
      extremely high metal-binding specificity. We further demonstrate that porcine
      Cox17 can also exist in partly oxidized (two disulphide bridges) and fully
      oxidized (three disulphide bridges) forms. Partly oxidized Cox17 can bind one Cu+
      or Zn2+ ion, whereas fully oxidized Cox17 does not bind metals. The metal-binding
      properties of Cox17 imply that, in contrast with other copper chaperones, Cox17
      is designed for the simultaneous transfer of up to four copper ions to partner
      proteins. Metals can be released from Cox17 by non-oxidative as well as oxidative
      mechanisms.

PMID- 15142041
TI  - Pre-transplant treatment of hepatocellular carcinoma: assessment of tumor
      necrosis in explanted livers.
AB  - Although liver transplantation (LT) is likely the most effective therapy for
      localized hepatocellular cancer (HCC), limited donor livers have resulted in
      prolonged waiting times for transplant. Pre-transplant therapy such as
      transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), and
      radiofrequency ablation (RFA) may be needed to sustain patients who are waiting.
      Records, imaging studies, and pathology to identify tumor necrosis on 15
      explanted livers with HCC were reviewed. Forty-nine nodules were removed from 15
      explanted livers. Five nodules in three livers that received no pre-transplant
      therapy were excluded from the study. Of the remaining 44 nodules in 12 patients,
      29 (66%) had 75% or more tumor necrosis. Fifteen nodules in five patients had
      <75% necrosis and these were due to local/non-local recurrences or perhaps
      suboptimal treatment with RFA, TACE or cisplatin gel injection. Mean waiting time
      for LT was 162.5 d. Nine of 13 patients had a different number of nodules when
      listed as were seen at explant, although stage changed in only three patients.
      One patient died 48 months post-LT (recurrent HCC), while the remaining patients
      are alive 2-55 months post-LT. We conclude that pre-transplant treatments for HCC
      are generally effective in achieving tumor necrosis. Factors involved in eventual
      extent of HCC seen at LT may include adequacy of treatment, accuracy of imaging
      techniques, local/non-local recurrences, and time waiting for transplant. We now
      need to determine if tumor necrosis can allow patients to wait longer for
      transplant and eventually affect long-term outcome.

PMID- 15142042
TI  - Use of lidocaine metabolism to test liver function during the long-term follow-up
      of liver transplant recipients.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the usefulness of the
      monoethylglycinexylidide (MEGX) test to monitoring the long-term function of
      liver allografts. METHODS: MEGX production was measured prospectively in 60
      consecutive liver transplant recipients undergoing their annual review. RESULTS:
      Median MEGX values in liver recipients (54 ng/mL; range 10-146) were lower than
      those found in healthy controls (78 ng/mL; range 44-118). MEGX values correlated
      negatively with alanine aminotransferase (ALT) activity (p = 0.004) and with the
      overall histological score (p = 0.01), and positively with sulfobromophthalein
      (BSP) and indocyanine green (ICG) clearances (p = 0.0002 and p = 0.002,
      respectively). A stepwise decline was observed with worsening liver fibrosis,
      from 71 +/- 5 microg/L in patients with no fibrosis to 27 +/- 9 microg/L in
      patients with bridging fibrosis (p = 0.002). BSP and ICG clearances correlated
      more closely than the MEGX test with the overall histological score (p = 0.001
      and p = 0.001, respectively) and portal fibrosis (p = 0.002 and p = 0.001).
      CONCLUSIONS: The measurement of MEGX formation is a simple and non-invasive
      method to monitor liver graft function. It may constitute a valuable tool for
      assessing the degree of fibrosis.

PMID- 15142043
TI  - Long time follow up of CD28- CD4+ T cells in living kidney transplant patients.
AB  - We previously reported that the CD28(-) CD4(+) T cell subpopulation was expanded
      in the kidney allograft patients with long graft survival, although these T cells
      were rarely found in patients with graft survival <5 yr. To understand the CD28(
      ) CD4(+) T cells in the long-term acceptance of kidney allografts, we examined
      functions of this population and performed a 4 yr follow up study. Peripheral
      blood mononuclear cells (PBMC) were obtained from 47 long-term living related
      kidney allograft recipients. CD28(+) CD4(+) and CD28(-) CD4(+) T cells purified
      by cell sorting were analyzed for expression of V(beta) repertoire. Donor
      specific response was examined in mixed lymphocyte reaction (MLR). A follow up
      study with long-term kidney allograft patients was performed for 4 yr about the
      rate of CD28(-) CD4(+) T cells. Eleven patients were examined by MLRs against
      donors and third party. Four patients with a marked increase of CD28(-) CD4(+) T
      cells showed the donor-specific responses appeared to be lower when compared with
      third party-specific responses. Freshly sorted CD28(-) CD4(+) T cells showed a
      restricted V(beta) repertoire, whereas the V(beta) usage of CD28(+) CD4(+) T
      cells from the same patients was much diversified. Such difference in V(beta)
      repertoire was not evident between the two populations from healthy control. A
      follow up study showed the ratio of CD28(-) CD4(+) T cells appeared to be lower
      in patients who were suspected of chronic rejection. These unusual CD4(+) T cells
      might be related to the long-term acceptance of human transplant allografts.

PMID- 15142044
TI  - Cost-minimization study comparing Simulect vs. Thymoglobulin in renal transplant
      induction.
AB  - PURPOSE: Based on the data of clinical trial CHI-F-02 comparing the efficacy and
      safety of basiliximab (Simulect) vs. anti-thymocyte globulin (Thymoglobulin) in
      renal transplant induction, we carried out an economic evaluation. METHOD: This
      pharmacoeconomic study was a cost-minimization study, i.e. given the equivalent
      efficacy of the products, the strategy that minimized the cost of care was
      considered better. The cost of care was analyzed from the hospital perspective.
      MATERIAL: This 'piggyback' study of 100 patients estimated the direct medical
      costs incurred over 6 months of use of two strategies for renal transplant
      induction therapy. Direct medical costs are those of utilized medical resources:
      medications, hospital stays, dialysis, and physician visits and investigations
      not scheduled in the protocol. RESULTS: In the Simulect arm, significant
      reductions were found in the initial hospital stay duration and number of
      infectious episodes. Therefore, although the average cost of treatment was
      slightly higher with Simulect) than with Thymoglobulin (2964 vs. 2298 Euros), the
      cost of the initial hospitalization was significantly lower in the Simulect arm
      (10 907 vs. 11 967 Euros; p = 0.02). Furthermore the mean cost of infectious
      episodes was significantly lower in the Simulect arm (1056 vs. 1790 Euros, p =
      0.03). Cytomegalovirus infection accounted for a significantly smaller proportion
      of this cost in the Simulect arm than in the Thymoglobulin arm (30% vs. 53%, p =
      0.001). CONCLUSION: This study showed direct medical cost savings of 1159 Euros
      per patient in the Simulect arm, which more than compensated for the higher price
      of this immunosuppressive drug.

PMID- 15142045
TI  - Preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions,
      splenectomy and DFPP-enabled non-responders to undergo ABO-incompatible kidney
      transplantation.
AB  - Patients undergoing ABO-incompatible kidney transplantation must have their anti
      donor blood-type antibody titer (ADBT) reduced to below 1:16 by using either
      plasma-exchange (PEX) or double filtration plasma exchange (DFPP) before they can
      safely undergo a transplantation. The ADBT can be reduced to under 1:16 in most
      cases; however, some cases (non-responders) do not respond to PEX or DFPP
      treatment. To enable kidney transplantations to be performed in non-responders,
      we developed a new preconditioning regimen consisting of anti-CD20 monoclonal
      antibody (rituximab) infusions, a splenectomy, and DFPP. Four non-responders were
      infused with rituximab at a dose of 375 mg/m(2) weekly for 3-4 wk and
      splenectomized 1 or 2 wk before transplantation. Four to five DFPP-sessions were
      then performed after the splenectomy. Using this preconditioning regimen, the
      ADBT was reduced to below 1:16, enabling kidney transplantations to be
      successfully performed in all patients. After the kidney transplantation, no
      episodes of humoral rejection were observed, and only one episode of cellular
      rejection was encountered. The cellular rejection was associated with a reduction
      in immunosuppressant administration because of CMV infection that occurred 80 d
      after the kidney transplantation. The renal allografts were functioning well in
      all patients after a mean follow-up period of 390 d. No serious complications or
      side effects were encountered. We have developed a new preconditioning regimen
      that enables PEX and DFPP non-responders to undergo ABO-incompatible kidney
      transplantations.

PMID- 15142047
TI  - The long-term outcome of kidney transplantation in patients under cyclosporine--a
      developing country experience.
AB  - The introduction of cyclosporine revolutionized the practice of solid organ
      transplantation. Although early studies showed better short-term results, the
      long-term benefits of cyclosporine appear to be more contentious. Our study
      investigated the outcome of sustained cyclosporine usage on patient and renal
      allograft survival in a developing country setting. All patients receiving
      primary renal transplants at our institution over a 23-yr period were included
      and data analysed for patient and graft survival rates using the Kaplan-Meier
      actuarial method. The patients receiving cyclosporine were compared with
      historical controls receiving conventional treatment. Early graft survival was
      superior in patients under cyclosporine but this benefit disappeared after the
      first year. There was no significant improvement in early patient survival in
      patients under cyclosporine but late survival was better in patients under
      conventional treatment. In our setting cyclosporine only improves early graft
      survival and does not have long-term benefit either on patient or graft survival.

PMID- 15142046
TI  - Impact of HCV infection on first cadaveric renal transplantation, a single center
      experience.
AB  - BACKGROUND: Controversy still persists regarding the impact of HCV infection on
      renal transplant recipients. This study aimed to evaluate the effect of anti-HCV
      antibody status on patients and grafts of renal transplants at a single center.
      METHODS: We examined 299 first cadaveric renal transplants performed between July
      1981 and May 2000 at our hospital, including 129 patients with anti-HCV antibody
      positive (HCV+ group) and 170 patients with anti-HCV antibody negative (HCV-
      group). The HBsAg of the 299 patients were all negative throughout the follow-up
      period. Causes of graft failure and patient death were analyzed. Patient and
      graft cumulative survival were compared between HCV+ and HCV- groups.
      Multivariate analysis with Cox proportional hazard model were calculated for risk
      hazards of outcome. RESULTS: Overall cumulative patient survival was 97.72, 85.63
      and 71.31% at 1, 10, and 15 yr, respectively, in the HCV+ group, compared with
      95.02, 67.85 and 59.83% at 1, 10 and 15 yr, respectively, in the HCV- group (p =
      0.014). The major cause of patient death in both groups was infection with 26.67%
      in HCV+ group and 60.87% in HCV- group. Cumulative graft survival in the HCV+
      group revealed 92.26, 55.97 and 26.16% at 1, 10 and 15 yr, respectively, compared
      with 88.07, 58.34 and 58.32% at 1, 10 and 15 yr, respectively, in the HCV- group
      (p = 0.700). The major cause of graft failure was chronic allograft dysfunction
      (56.82%) in HCV+ group, and patient death (32.43%) in the HCV- group.
      Multivariate analysis of patient survival revealed anti-HCV antibody+ had lesser
      risk hazard (aRR: 0.30, p = 0.002), chronic hepatitis had higher risk hazard
      (aRR: 1.90, p = 0.135), male recipient had higher risk hazard (aRR: 2.18, p =
      0.051), and older recipients (age >55) also had higher risk hazard (aRR: 4.21, p
      = 0.063). Analysis of graft survival revealed only older donors (age >35) had
      higher risk hazard (aRR: 1.90, p = 0.081). CONCLUSIONS: The study revealed that
      patients with anti-HCV antibody had higher incidence of chronic hepatitis,
      chronic allograft dysfunction and post-transplantation nephrotic syndrome. Graft
      survival tended lower in the very long time. However, patients with anti-HCV
      antibodies had better patient survival when compared with patients without HCV
      antibodies up to 15 yr follow up. Patients of hepatitis C group without clinical
      chronic hepatitis was associated with best patient survival.

PMID- 15142049
TI  - Molecular markers in subclinical acute rejection of renal transplants.
AB  - In this study, we evaluated the expression of molecular markers of acute
      rejection in protocol biopsies of patients with and without subclinical acute
      rejection (SAR). Protocol biopsies were performed at 2 months (n = 21) and 12
      months (n = 14) after kidney transplantation in patients with stable allograft
      function. After biopsy tissue RNA isolation, reverse transcription and polymerase
      chain reaction (RT-PCR) for the glyceraldehyde 3-phospate dehydrogenase (GAPDH),
      perforin, granzyme B and Fas ligand genes were performed. The Banff 97
      classification was used for histological diagnosis. Creatinine concentrations at
      2 months were significantly higher in patients with SAR (1.46 +/- 0.27 x 1.18 +/-
      0.24; p < 0.02). Perforin transcripts were found in 15 biopsy specimens, 10 of
      which had histological signs of SAR (p = 0.06). Granzyme B expression was found
      in 10 specimens, nine of which had SAR (p < 0.01). Fas ligand was expressed in
      seven specimens, and six of them were classified as SAR (p < 0.01). Perforin
      expression had the highest sensitivity (81%) for the diagnosis of SAR. Granzyme B
      and Fas ligand had specificity of 90%. At 12 months, there was no significant
      difference in creatinine concentrations for patients with and without previous
      SAR (1.63 +/- 0.57 x 1.28 +/- 0.31; p = 0.10). Molecular analysis revealed that
      there was no statistically significant difference in the expression of perforin
      and granzyme B in patients with and without SAR. Fas ligand expression was
      observed in five samples, four of which had histological signs of SAR (p = 0.03).
      At 12 months, perforin expression had the highest sensitivity (83%), and Fas
      ligand, the highest specificity (88%) for the diagnosis of SAR. We concluded that
      the expression of genes that encode proteins involved in the cytolytic attack
      against the allograft is increased in kidneys with SAR. These findings support
      the understanding that SAR is an active immune process potentially deleterious to
      renal allografts.

PMID- 15142048
TI  - A long-term study on hyperlipidemia in stable renal transplant recipients.
AB  - OBJECTIVES: Hyperlipidemia is a common and important risk factor after renal
      transplantation, but there is little long-term data on its incidence, pattern,
      and evolution in stable renal allograft recipients on low dose maintenance
      immunosuppression. PATIENTS AND METHODS: A retrospective study was conducted on
      all patients who received kidney transplants from April 1, 1990 to March 31, 2000
      at a single center, on their serial lipid profile during the first 3 yr after
      kidney transplantation. RESULTS: A total of 221 (122 male, 99 female; mean age
      37.8 +/- 10.0 yr at the time of transplantation) Chinese adult renal allograft
      recipients were included. A 95.3% of patients were on cyclosporine and
      prednisolone based immunosuppression. Increases in total cholesterol (TC), low
      density lipoprotein (LDL), and high density lipoprotein (HDL) were noted, while
      the level of triglyceride (TG) decreased after renal transplant. The incidence of
      hypercholesterolemia (defined as TC >/= 6.3 mmol/L or LDL >/= 4.2 mmol/L) within
      the first year was 28.2 and 20.3%, respectively. The incidence rate decreased
      significantly in the second (5.4%, p = 0.000 and 6.4%, p = 0.003) and third year
      (9.5%, p = 0.003 and 4.9%, p = 0.021), but the incidence of patients having a
      high risk-ratio (defined as TC/HDL >/= 5) remained unchanged (6.9, 4.9 and 10.3%
      within the first, second, and third year, respectively). Treatment with statin
      was necessitated in 6.8, 13.6 and 21.7% of the patients at 1, 2, and 3 yr after
      transplantation, respectively. The prevalence rates of elevated TC and LDL were
      18.3 and 18.9% at baseline, 40.6 and 33.3% after 1 yr, 32.8 and 27.3% after 2 yr,
      and 24.8 and 19.0% after 3 yr, despite treatment. The prevalence of patients with
      a high risk-ratio was 45.0% at baseline, 30.5% after 1 yr (p = 0.002), 22.6%
      after 2 yr (p = 0.000) and 21.8% after 3 yr (p = 0.000). Hypercholesterolemia at
      the time of transplantation was an independent predictor for post-transplant
      hypercholesterolemia (odds ratio 3.76, 95% confidence interval 1.47-9.62, p =
      0.006). CONCLUSION: Renal transplantation is associated with a characteristic
      pattern of dyslipidemia, with increased TC, LDL and HDL, and a decrease in TG.
      Patients with pre-existing hypercholesterolemia were at higher risk for post
      transplant hypercholesterolemia. Although the incidence of hypercholesterolemia
      peaks within the first year after transplantation, this remains a long-term
      complication in a significant proportion of patients on low dose
      immunosuppressive medications.

PMID- 15142050
TI  - Apolipoprotein E gene polymorphism in renal transplant recipients: effects on
      lipid metabolism, atherosclerosis and allograft function.
AB  - INTRODUCTION: Atherosclerosis is a serious complication and leading cause of
      mortality in renal transplant recipients (RTRs). Hyperlipidemia may be associated
      with progression of renal disease and chronic allograft dysfunction. Similarities
      in the pathogenesis of glomerulosclerosis and atherosclerosis have been proposed.
      Apolipoprotein (apo) E gene code forms three major isoforms (E2, E3, and E4) with
      variable effects on lipid metabolism. PATIENTS AND METHODS: A total of 118
      patients, at a mean age of 40 +/- 8 yr, were included in the study. Apo E
      genotyping was carried out on genomic DNA using polymerase chain reaction and
      restriction enzyme. Carotid artery intima media thickness and atherosclerotic
      plaques were evaluated by B-mode ultrasonography. The plasma levels of lipids and
      lipoproteins and acute phase reactants were also studied. Allograft function was
      evaluated by measuring serum creatinine and creatinine clearance values. RESULTS:
      The frequencies of E2, E3, and E4 alleles were 0.10, 0.78, and 0.12 respectively.
      Carotid artery atherosclerosis was found in 25% of E2 carriers, 30% of E3
      carriers, and 57% of E4 carriers. Total cholesterol, total triglyceride, low
      density lipoprotein, very low-density lipoprotein, apo B 100 levels were found to
      be higher in apo E4 carriers. Median apo A1 level was higher and allograft
      functions were better in apo E2 carriers (p < 0.05). Multiple regression analysis
      showed that allograft functions were negatively correlated with elevated acute
      phase reactants (p < 0.01) and only the age, but not the apo E genotypes, was an
      independent risk factor for atherosclerotic vascular disease (p < 0.01).
      DISCUSSION: The pathogenetic events linking lipid metabolism and allograft
      functions and development of atherosclerosis are complex and multifactorial in
      RTRs. Our results showed that apo E genotypes have influences on lipids,
      lipoproteins and allograft functions. The ultimate role of apo E4 gene
      polymorphism as a risk factor for development and progression of atherosclerosis
      in RTRs should be sought in further studies.

PMID- 15142051
TI  - Outcome of lamivudine resistant hepatitis B virus mutant post-liver
      transplantation on lamivudine monoprophylaxis.
AB  - BACKGROUND: We aimed to investigate the clinical outcome of patients who develop
      lamivudine resistant hepatitis B virus mutants (YMDD mutants) after liver
      transplantation. METHODS: Patients who received liver transplantation for
      hepatitis B-related liver diseases from 1999 to 2002 were studied. All patients
      received lamivudine monotherapy before and after liver transplantation. HBsAg and
      HBV DNA were regularly monitored, and YMDD mutation was detected by direct
      sequencing. RESULTS: Twenty patients were followed up for median 94 wk (range: 15
      177 wk) post-liver transplantation. Six patients developed YMDD mutants, and the
      cumulative probability of developing YMDD mutations post-liver transplantation
      was 21% in 1 yr and 34% in 2 yr. One patient developed YMDD mutants before liver
      transplantation and died of hepatitis reactivation and liver failure 15 wk post
      transplantation. The other five patients developed YMDD mutants 32-72 wk after
      liver transplantation. Two of them developed severe hepatitis which responded
      promptly to adefovir dipivoxil. The remaining three patients with YMDD mutants
      had minimal to mild hepatitis. The cumulative survival for patients with YMDD
      mutants was 83% and 28% at 1 and 2 yr, respectively. Only one patient who did not
      develop YMDD mutants died at week 119 due to chronic rejection. The post
      transplant survival for patients with YMDD mutants was significantly poorer than
      those without YMDD mutants (log rank test p = 0.083). CONCLUSIONS: The emergence
      of YMDD mutants after liver transplantation on lamivudine monoprophylaxis had
      wide range of clinical presentations and was associated with increased mortality.

PMID- 15142052
TI  - Optimizing open live-donor nephrectomy - long-term donor outcome.
AB  - INTRODUCTION: The technique of laparoscopic or retroperitoneoscopic donor
      nephrectomy has been increasingly propagated in recent years. The central
      advantage is supposed to be a reduction of perioperative discomfort. However,
      there have not been many reports describing the subjective feeling associated
      with an open donor nephrectomy, particularly with respect to the pain level in
      the perioperative and long-term course. This retrospective study examines the
      perioperative pain and morbidity and long-term outcome of living kidney donors
      from 35 yr of experience at the University Hospital Benjamin Franklin of the Free
      University of Berlin. METHODS: A total of 102 living kidney donors were asked to
      fill out a questionnaire. Five epidemiological questions were posed and the rest
      dealt mainly with lasting subjective and objective surgical impairments. There
      were also questions relating to the perioperative pain level (VAS/NAS-Score). In
      addition, basic information was obtained regarding the donor's current health
      status (physical examination, serum creatinine; sometimes also ultrasound,
      protein IU, blood pressure), and/or examinations were performed. RESULTS: The
      mean age at the time of donation was 45.5 and 55% were women. Donor nephrectomies
      were left-sided in 78 cases and right-sided in 24. There was a total complication
      rate of 53%, but serious complications only occurred in two cases (1.9%). A total
      of 53 donors could be reached. Although 41.5% felt they had a lasting impairment,
      somatic sequelae like respiratory, abdominal or scar problems were rare,
      affecting a maximum of only four patients in each case. Fifteen patients reported
      neurological problems such as sensory disturbances. The mean serum creatinine was
      89.9 micromol/L in female and 114.2 micromol/L in male donors. Microalbuminuria
      was found in 22.6% of the donors, hypertension in 35.8%. Persistent pain was
      reported by 20.7%, its occurrence being permanent in two of the donors and very
      frequent in one. All the others rarely have pain. The median perioperative
      VAS/NAS score was 8 on the first day after surgery, 5 after 1 wk and 1 after 1
      month. The analgesia was rated as good or very good by 71%. Everyday life was
      managed as well as before surgery after 2-4 wk by the highest percentage (42%) of
      patients, but working capacity was only regained after 1-3 months by a comparable
      percentage (44%). Forty-six percent had a very good and 33% a good feeling after
      the kidney donation. The relationship to the recipient had intensified in most
      cases. Ninety-one percent would again decide in favor of a donation. CONCLUSION:
      Donor nephrectomy in an open technique is a safe and reliable procedure with low
      morbidity. After a median post-operative period of 7 yr, however, 42% of the
      donors still report general impairment due to the intervention, although concrete
      somatic problems were only detected in a few cases. Nearly all these patients
      underwent surgery in a full flank position. Wound-healing impairments were also
      significantly more frequent with this surgical technique. This positioning should
      thus be avoided. The post-operative pain level was relatively high, but a marked
      improvement was achieved in the course of the observation period by optimizing
      analgesic management.

PMID- 15142053
TI  - Gastroparesis following kidney/pancreas transplant.
AB  - This pilot study examined associations among patterns of gastric myoelectrical
      activity, symptoms of gastroparesis, years of diabetes, months of dialysis, and
      use of gastrointestinal medications in gastroparetic kidney-pancreas (KP)
      transplant recipients. Electrogastrography (EGG) and gastric symptom data were
      obtained from 42 transplant recipients before and after transplant (6, 12, and 24
      months). Recipients were 38 +/- 7 yr of age, 88% Whites, and 60% male; 97% had
      hypertension. All had functioning grafts post-transplant (mean creatinine, 1.59
      +/- 0.66 mg/dL, and serum glucose 91.97 +/- 24.92 mg/dL). Sixteen subjects had
      normal EGG (2.7-3.2 cycles per minute, cpm); two were tachygastric (>3.2 cpm) at
      all time points; one remained bradygastric (<2.7 cpm) throughout the study
      period. Following transplant, symptoms lessened and were associated with 6-month
      normalization of EGG (r = 0.41, p = 0.02). A small change in the percentage of
      patients with normal EGG was observed from baseline to 24 months (67% vs. 69%
      respectively); however, there was a shift from bradygastria (29% to 15%
      respectively) to tachygastria (5% to 15% respectively). Prescribed prokinetic and
      antisecretory medications use increased over the study period from 13 (31%)
      subjects at baseline to 32 (86%) at 6 months; 21 (78%) at 12 months; and 12 (92%)
      at 24 months. Although symptoms diminish following transplant, gastroparesis
      remains a significant problem for transplant patients. Normalization of EGG and
      shifts from bradygastria to tachygastria occur post-transplant. Our results
      suggest that serial EGGs and frequent assessment of symptoms can be used to
      follow gastroparesis in KP recipients.

PMID- 15142054
TI  - A decision-analytic economic evaluation of valaciclovir prophylaxis for the
      prevention of cytomegalovirus infection and disease in renal transplantation.
AB  - OBJECTIVE: This analysis evaluates the cost-effectiveness of valaciclovir
      prophylaxis using clinically and economically important health outcomes including
      graft failure, life-years, and quality-adjusted life-years (QALYs). METHODS: A
      Markov model was developed using a randomized, placebo-controlled trial of
      valaciclovir prophylaxis, together with a published epidemiological study and
      national renal transplant registry data. The model's population was stratified
      into two risk groups by donor/recipient cytomegalovirus (CMV) serostatus at
      transplantation: donor-positive/recipient-negative (D+R-) and recipient-positive
      (R+) patients. The model estimated costs and health outcomes over a 30-yr period
      from the perspective of Australian health care providers. RESULTS: The total
      health care cost was $3619 lower for D+R- patients receiving valaciclovir
      prophylaxis compared with those not receiving prophylaxis. D+R- patients
      receiving valaciclovir gained an extra 0.33 yr of life and 0.27 QALYs. R+
      patients receiving valaciclovir prophylaxis gained an extra 0.07 yr of life and
      0.05 QALYs, with an incremental cost of $914. This equates to $17 127 per QALY
      gained, which is highly cost-effective compared with other drugs and health
      interventions. CONCLUSIONS: Valaciclovir for the prophylaxis of CMV disease in
      renal transplant recipients is a cost-effective intervention, significantly
      reducing the burden of CMV disease to patients and health care providers.

PMID- 15142055
TI  - Persistent dipstick haematuria following renal transplantation.
AB  - Despite widespread testing for dipstick haematuria following renal
      transplantation, there are no published series describing the prevalence and
      possible causes of this complication in an adult population. A cross-sectional
      study of 640 renal transplant recipients under review at our follow-up clinic was
      performed. Persistent haematuria was defined as a minimum of 1+ of blood on
      urinalysis stick testing detected at not fewer than 75% of clinic visits since
      its onset, or since the start of routine testing, present over a period of at
      least 4 weeks. The prevalence of persistent dipstick haematuria was 13.3%. Median
      serum creatinine was higher in patients with persistent haematuria but age,
      gender and length of time since transplantation were not significantly different.
      Potential explanations for persistent haematuria in 21 of 85 affected patients
      were chronic infection, ureteric stent without chronic infection, regular or
      intermittent self-catheterization, persistent menstrual bleeding, anticoagulant
      therapy, graft calculus, and allograft renal cell carcinoma. Recurrent or de novo
      glomerular disease was confirmed by graft biopsy in 10 of 85 patients. Among the
      41 recipients whose original cause of renal failure was IgA nephropathy (IgAN),
      the prevalence of persistent haematuria was 31.7% compared with 12% in the
      remaining patients (relative risk 2.6, 95% CI: 1.6-4.3). Persistent haematuria in
      IgAN patients was not associated with gender, age or time since transplantation.
      After 29 months of follow-up, 20% of patients with haematuria had progressed to
      graft failure or death compared with 11.6% of the unaffected group (p = 0.029).
      However, despite the association with earlier graft failure, haematuria did not
      predict this endpoint independently of renal function.

PMID- 15142056
TI  - Acute renal transplant injury and interaction between antithymocyte globulin and
      pooled human immunoglobulin.
AB  - The increasing number of highly sensitized patients awaiting renal
      transplantation has prompted the use of induction immunosuppression regimens
      including pooled human intravenous immunoglobulin (IVIG) combined with polyclonal
      anti-lymphocyte sera. We report a case of a patient who received a live donor
      transplant after abrogation of donor-specific positive cytotoxic crossmatch by
      IVIG. She developed early acute tubular injury associated with IVIG, mannitol,
      and hypertonic saline infusion. Furthermore, a possible interaction between IVIG
      and rabbit antithymocyte globulin (ATG) occurred, suggested by an increased
      number of peripheral CD3(+) lymphocytes after initial rapid lymphodepletion. We
      suggest that IVIG-associated nephrotoxicity should be considered in the
      differential diagnosis of early allograft dysfunction, and furthermore, that IVIG
      may interact with polyclonal antilymphocyte serum to affect the amount of
      lymphodepletion achieved.

PMID- 15142058
TI  - Living donor transplantation of a pelvic kidney.
AB  - Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation.
      We describe a successful case of living-donor transplantation using a pelvic
      kidney in a 17-month-old infant with congenital renal dysplasia. The recipient
      had exhausted all options for renal replacement therapy, and urgent
      transplantation was considered a life saving treatment.

PMID- 15142057
TI  - Severe hemolytic anemia due to passenger lymphocytes after living-related bowel
      transplant.
AB  - BACKGROUND: Hemolytic anemia following solid organ transplant may be caused by
      'passenger' lymphocytes producing antibodies against erythrocytes. This
      phenomenon has never been described after intestinal transplant. MATERIALS AND
      METHODS: We report a case of severe, immune-mediated hemolysis due to symptomatic
      passenger lymphocyte syndrome (PLS) in a 4-yr-old recipient of living donor small
      bowel transplant. The Coombs'-positive hemolysis was caused by anti-A,B
      antibodies derived from donor lymphocytes in an ABO-compatible donor-recipient
      pair (O into A). RESULTS: This complication was successfully and efficiently
      treated by the novel combined use of group O RBC transfusion, plasmapheresis and
      rituximab (anti-CD20). CONCLUSIONS: A severe hemolytic anemia due to PLS can
      occur in bowel transplantation. This complication should be considered when
      performing ABO-incompatible bowel transplant with a blood group O donor and an A
      or B recipient. Treatment with plasmapheresis, blood group O transfusion and
      rituximab has proved successful in our case.

PMID- 15142061
TI  - The assessment of topical nasal drug distribution.
AB  - The mainstay of treatment of chronic rhinosinusitis is through the administration
      of topical nasal drugs. The delivery and intranasal distribution of these is
      therefore of potential clinical significance. Until there is progress in the
      nasal drug distribution assessment methodology, it will be difficult to improve
      topical nasal drug delivery, which is known to be suboptimal in many ways. This
      study reviews intranasal drug delivery assessment methods, the present knowledge
      and explores future directions for research.

PMID- 15142062
TI  - Prospective evaluation of the value of direct referral hearing aid clinic in
      management of young patients with bilateral hearing loss.
AB  - The purpose of this study was to evaluate the value and effectiveness of a direct
      referral hearing aid clinic (DRHAC) in providing appropriate hearing aids to
      young patients aged 18-60 years while at the same time identifying patients with
      significant ear disease who need an otologist's opinion. The patients were
      referred to a tertiary referral hearing assessment clinic. A total of 137
      patients (18-60 years) met the criteria to be included in the study to be
      assessed in the clinic by both an audiometrician and an otologist. The main
      outcome measures were hearing evaluation and audiometrician's management. Of
      them, 114 patients attended the research clinic (83%), 23 patients (17%) did not
      attend the clinic and 57 patients (51%) did not need any treatment or further
      investigation as their hearing was normal or near normal. Thirty patients (27%)
      were given hearing aids. Twenty-five patients (22%) failed the audiometrician
      assessment and were referred to the otologist. Only 13 (18%) of the 25 patients
      referred for an otological opinion actually required further investigations,
      medical or surgical treatment. DRHAC is as viable a system in the younger as in
      the elderly population.

PMID- 15142063
TI  - Anterosuperior anchoring myringoplasty technique for anterior and subtotal
      perforations.
AB  - Anterior and subtotal tympanic perforations are difficult perforations to repair.
      We used the anterosuperior anchoring technique to repair 105 of those
      perforations. Our technique utilizes a large temporalis fascia graft using an
      underlay technique with due emphasis on anterosuperior anchorage. The success
      rates in paediatric myringoplasty for consultant solo (J.R.K.) and trainees under
      supervision were 100% and 85.7%, respectively. The overall success rates in adult
      myringoplasty for consultant solo and trainees under supervision were 93.8% and
      82.4%, respectively. Analysis of the 82 successful cases showed statistically
      significant improvement in air conduction thresholds after myringoplasty at 500
      Hz (P < 0.01), 1 kHz (P < 0.05), 2 kHz (P < 0.01) and 4 kHz (P < 0.01). Our study
      showed that the anterosuperior anchoring technique produced excellent results in
      the repair of challenging anterior and subtotal perforations in both adults and
      children.

PMID- 15142064
TI  - Quality of life in patients with vestibular schwannomas managed conservatively.
AB  - Since the era of magnetic resonance imaging (MRI) scanning, vestibular
      schwannomas are being diagnosed earlier, growth has been shown to be static in up
      to 70% of cases and patients have admitted to a reduced quality of life following
      acoustic neuroma surgery. The aim of this study was to assess the quality of life
      in patients with vestibular schwannomas managed conservatively. Fifty patients
      with a vestibular schwannoma were identified who were being managed by interval
      MRI scanning. Fifty patients attending the general otolaryngology clinic with
      similar symptoms were prospectively recruited. Each group was assessed using the
      short form 36 (SF-36) health survey. Both groups were adequately age and sex
      matched and the SF-36 scores were comparable across all eight health domains.

PMID- 15142065
TI  - Decreasing test time in newborn hearing screening.
AB  - This study examined the effect of reducing the number of accepted responses in
      transiently evoked otoacoustic emissions based on the results of a universal
      neonatal hearing screening program. Our intention was to decrease the test time
      of newborns. A total of 464 ears were examined by using a universal newborn
      hearing-screening program implemented in a private maternity hospital. ILO88
      Otodynamics Analyzer Quickscreen program was used for all testing and a two-stage
      procedure was adopted. In the first stage, the results were continuously
      evaluated for the 'pass' criteria, during the test, after at least 20 low-noise
      sweeps had been presented. As soon as the criteria were met, the test was
      interrupted and the results were recorded. In the second stage of the procedure,
      the test was continued and finally terminated after 260 quiet samples had been
      recorded. The results of each stage of this procedure were compared and
      evaluated. A total of 402 ears had normal otoacoustic emissions and only 62 ears
      had absent emissions. It was concluded that after a minimum of 20 averaged quiet
      responses, which we consider necessary in order to record reliable emissions and
      as soon as the 'pass' criteria were fulfilled the test could be terminated
      without affecting the 'pass-fail' rates which were similar in both stages.
      However, we believe that for diagnostic and clinical purposes, all 260 quiet
      samples must be used, because the results after the second stage indicated
      statistically better scores in response and reproducibility measures.

PMID- 15142066
TI  - Ginkgo biloba does not benefit patients with tinnitus: a randomized placebo
      controlled double-blind trial and meta-analysis of randomized trials.
AB  - The objective was to ascertain if Ginkgo biloba benefits patients with tinnitus.
      The study design was: 1. Randomized double blind trial of Ginkgo biloba versus
      placebo; 2. A meta-analysis of randomized placebo controlled double blind trials.
      Participants included 66 adult patients with tinnitus and six (including our
      study) randomized placebo controlled double blind trials were meta-analysed. The
      main outcome measures were the Tinnitus Handicap Inventory (THI), Glasgow Health
      Status Inventory (GHSI) and average of hearing threshold at 0.5, 1, 2, 4 kHz. In
      the meta-analysis the proportion of patients gaining benefit and an overall odds
      ratio were determined. The results showed the mean difference in change of the
      THI, GHSI and hearing between Ginkgo biloba (n = 31) and placebo group (n = 29)
      was 2.51 (CI -10.1, 5.1, P = 0.51), 0.58 (CI-4.8, 3.6, P = 0.38) and 0.68 db (CI 
      4.13, 2.8, P = 0.69). Meta-analysis revealed 21.6% of Ginkgo biloba treated
      patients (n = 107/552) gained benefit versus 18.4% (n = 87/504) of placebo
      treated patients with an odds ratio of 1.24 (CI 0.89, 1.71). In conclusion,
      Ginkgo biloba does not benefit patients with tinnitus.

PMID- 15142067
TI  - Hyperventilation in the vestibular clinic: use of the Nijmegen Questionnaire.
AB  - The objective of the present study was to determine the prevalence of
      hyperventilation syndrome in patients seen for vestibular assessment and to
      assess the clinical utility of the Nijmegen Questionnaire in this group. The
      Nijmegen Questionnaire and Dizziness Handicap Inventory (DHI) were administered
      prospectively to a consecutive series of 100 patients identified as candidates
      for vestibular assessment within the University Hospital Neuro-otology practice.
      Twenty-three per cent of patients seen for vestibular assessment were diagnosed
      with hyperventilation syndrome using the Nijmegen Questionnaire. Seventeen of
      these (74%) would have remained undetected had the Nijmegen questionnaire not
      been used. No relationship was found between vestibular assessment results and
      either Nijmegen or DHI scores. A significant correlation was found between DHI
      scores and Nijmegen Questionnaire scores (rho = 0.348, P = 0.0005). In
      conclusion, the Nijmegen Questionnaire is a quick, easy to administer and low
      impact assessment tool for hyperventilation syndrome and is a useful adjunct to
      the otological consultation. Diagnosed patients can then be offered breathing
      control exercises as part of a vestibular rehabilitation programme.

PMID- 15142068
TI  - The effects of L-carnitine on presbyacusis in the rat model.
AB  - Reactive oxygen metabolites are products of oxidative metabolism that are
      continuously generated in vivo, and are known to produce serious cellular, tissue
      and genomic damage. l-carnitine is an endogenous amine that has been shown to
      have an effect on the synthesis of reactive oxygen metabolites. Twenty Wistar
      rats, 24 months of age, were randomly assigned to two groups as control and l
      carnitine treatment groups. One millilitre of distilled water was administered to
      control rats and 50 mg/kg l-carnitine to rats of l-carnitine treatment groups by
      intragastric gavage once a day for 30 days. At the end of 30 days, all groups
      underwent auditory brainstem response testing after administration of
      intraperitoneal urethane anaesthesia. l-carnitine treatment reduced III, V
      latencies and I-III, III-V and I-V interpeak latencies (IPL) significantly
      compared with the control group. l-carnitine treatment improved age-related
      deterioration in auditory pathways and hence may be a new alternative for the
      treatment of presbyacusis.

PMID- 15142069
TI  - Is acoustic analysis of snoring an alternative to sleep nasendoscopy?
AB  - Previous studies have suggested that acoustic analysis may be useful in
      distinguishing different types of snoring prior to possible corrective surgery.
      This study aimed to establish whether it could replace sleep nasendoscopy in a
      clinical setting. Thirty-five patients undergoing sleep nasendoscopy had their
      snoring recorded and analysed using commercially available equipment. It was
      found that centre frequency can be used to distinguish pure palatal from tongue
      base snoring, with a clear cut-off value of 90 Hz between the two. Multisegmental
      snoring cannot be identified on the basis of centre frequency alone. It may be
      distinguished from tongue base, but not palatal snoring by the nature of the
      frequency distribution plot (sensitivity 77%, specificity 81%). Blinded
      assessment of waveforms of individual snores gave poor accuracy (53%) and poor
      interobserver agreement (kappa = 0.10). Acoustic analysis may help screen for
      pure tongue base snoring. However, we feel that it is unlikely to replace sleep
      nasendoscopy.

PMID- 15142070
TI  - The role of atopy in Maltese patients with chronic rhinitis.
AB  - The global prevalence of allergic rhinitis has been on the increase and recent
      clinical experience in Malta has shown a similar trend. The aim of this study was
      to investigate the role of atopy in 415 patients presenting with rhinitis of at
      least 3 months duration, and to identify the common allergens responsible.
      Presenting clinical features, past and family history of seasonal allergic
      symptoms, exposure to cigarette smoking, pet ownership and occupation were
      analysed. All patients were skin tested for common allergens. Fifty-five per cent
      of patients were atopic, the main allergens responsible being house dust mite,
      cat dander and grass pollen. Rhinorrhoea and sneezing were significantly more
      common in atopic patients, who were more likely to have a past history and family
      history of seasonal asthma, eczema or rhinoconjunctivitis. Skin test-negative
      patients with idiopathic rhinitis were mostly females and tended to present a
      decade later. Differentiation between atopic and idiopathic chronic rhinitis may
      be helpful in the clinical setting in order to help predict response to
      treatment.

PMID- 15142072
TI  - Mucociliary clearance after external dacryocystorhinostomy.
AB  - We investigated the nasal mucociliary clearance time in 17 patients who underwent
      a primary unilateral external dacryocystorhinostomy operation. Mucociliary
      clearance function in both nasal cavities was assessed with the saccharin test.
      The results were compared with each other using paired samples t-test. We found
      significantly worse mucociliary clearance time on the operated side (mean: 6.3
      min) than on the non-operated side (mean: 5.5 min) (P = 0.004). External
      dacryocystorhinostomy negatively affected the mucociliary clearance function in
      this study.

PMID- 15142071
TI  - A prospective single-blind randomized-controlled trial comparing two surgical
      techniques for the treatment of snoring: laser palatoplasty versus uvulectomy
      with punctate palatal diathermy.
AB  - The aim of this study was to compare laser palatoplasty with uvulectomy with
      punctate palatal diathermy as treatment modalities for snoring. The study design
      was a prospective, single-blind, randomized-controlled trial. Eighty-three
      patients entered the trial. After a mean follow-up period of more than 18 months
      there was no statistically significant difference between the two groups
      regarding the patient perception of benefit from surgery or the subjective
      improvement in snoring. However, there was a statistically significant difference
      in the degree of pain in the immediate postoperative period (mean difference =
      22.14, 95% CI = 7.98-36.31, P = 0.003), with the pain being worse in the laser
      palatoplasty group. Relative risk of complications for laser palatoplasty was
      1.42 (95% CI = 0.93-2.17). The snoring scores and Glasgow Benefit Inventory
      scores decreased with time in both the groups but there was no statistically
      significant difference between the two groups.

PMID- 15142074
TI  - Stomal recurrence after primary total laryngectomy.
AB  - Stomal recurrence after total laryngectomy is usually considered to be incurable.
      A total of 402 patients suffering from squamous cell carcinoma of the larynx
      treated by total laryngectomy during the period 1982-96 were analysed. In the
      group of patients studied, the significant risk factors for stomal recurrence
      were glottic-subglottic tumour localization and regional tumour spread.
      Postoperative radiotherapy can significantly reduce the risk of stomal
      recurrence.

PMID- 15142073
TI  - A prospective, single-blind, randomized controlled trial of petroleum
      jelly/Vaseline for recurrent paediatric epistaxis.
AB  - The aim of the study was to determine if petroleum jelly was an effective
      treatment for paediatric epistaxis. A single-blind, prospective, randomized
      controlled trial was undertaken in an otolaryngology outpatient clinic of a
      paediatric hospital from March 2001 to March 2002. A total of 105 children
      referred with recurrent epistaxis were randomized into the study, 52 into the
      treatment arm and 53 into the control arm. Children in the treatment arm applied
      Vaseline twice a day bilaterally for 4 weeks and were monitored for any bleeds
      for the next 4 weeks. Children in the control arm were simply given an 8-week
      appointment and the number of bleeds were monitored for the 4 weeks prior to
      their appointment. The outcome measure was the proportion of children in each
      group without nosebleeds in the preceding 4 weeks. Both groups were equally
      distributed in age, duration of symptoms and duration of each bleed. Fourteen of
      51 (27.5%) patients of the treatment arm and 18 of 53 (34%) of the control arm
      did not bleed in the 4 weeks before review (chi-square test, P = 0.472). It can
      be concluded that Vaseline alone confers no benefit over simple observation in
      recurrent childhood epistaxis.

PMID- 15142075
TI  - Quality of life following resection, free flap reconstruction and postoperative
      external beam radiotherapy for squamous cell carcinoma of the base of tongue.
AB  - This study was conducted to evaluate quality of life in a cohort of patients with
      squamous cell carcinoma of the tongue base, treated with primary surgery,
      reconstruction and postoperative radiotherapy. Twelve patients were assessed in a
      cross-sectional study using the University of Washington Quality of Life
      Instrument (UW-QOL). All patients underwent external beam irradiation following
      primary resection of their tumour and reconstruction. Patients on average
      reported their overall and health related QOL to be good. Functionally they had
      good pain control, speech intelligibility, activity and recreational levels.
      There were some limitations in chewing, swallowing and taste. The results suggest
      that surgical resection can offer good functional and overall QOL results for
      advanced tumours when combined with reconstruction. The morbidity associated with
      postoperative radiotherapy includes reduced swallowing, taste, saliva production
      and difficulty chewing.

PMID- 15142076
TI  - Gold weight implants in the management of lagophthalmos in facial palsy.
AB  - The otolaryngologist plays an essential role in the diagnosis and management of a
      facial palsy. We present one of the largest cohort prospective studies in the UK
      of 22 patients with gold weight implants, including ancillary oculoplastic
      techniques, and their outcomes. Facial paralysis places the eye at risk and
      protection and lubrication of the eye is paramount in the management of these
      patients. If recovery of facial function is likely to be delayed or negligible,
      gold weight loading of the upper lid has been shown to be effective in providing
      a dynamic solution to lagophthalmos. Following surgery, complete eye closure was
      possible in the upright position in 18 patients (82%). Two patients had their
      weights removed secondary to infection (9%). At long-term follow up, four
      patients judged their vision to have deteriorated (29%). Two of these, after
      investigation by the ophthalmologists, were found to have pressure astigmatism
      and removal corrected the visual problems. Overall patient satisfaction with the
      procedure is high and all reported improvement in eye closure following the
      operation. An algorithm for the management of the eye in patients with facial
      palsy is outlined.

PMID- 15142077
TI  - Combating antibiotic resistance.

PMID- 15142078
TI  - Does asbestos cause laryngeal cancer?

PMID- 15142079
TI  - Management of suspected foreign body aspiration in children.

PMID- 15142080
TI  - Response to 'Is it necessary to screen for hearing loss in the pediatric
      population with osteogenesis imperfecta?'.

PMID- 15142081
TI  - Use of pupil size and reaction to detect orbital trauma during and after surgery.
AB  - We describe how pupillary reactions, used as an index of optic nerve function,
      can be elicited using only one working pupil. This is to challenge the conclusion
      of a study that did not appreciate this physiological phenomenon and thus gave
      rise to erroneous conclusions that might otherwise limit the scope of pupil
      measurements during and after surgery. For suitable cases, non-opioid anaesthesia
      and further clinical development of pupillometry are suggested by us as measures
      to monitor optic nerve function.

PMID- 15142083
TI  - Should patients with asymmetrical noise induced-hearing loss be screened for
      vestibular schwannomas?

PMID- 15142085
TI  - Efficacy of icepacks in the management of epistaxis.

PMID- 15142087
TI  - Does excessive occlusal load affect osseointegration? An experimental study in
      the dog.
AB  - AIM: The purpose of this study was to evaluate the effect of excessive occlusal
      load following placement of titanium implants in the presence of healthy peri
      implant mucosal tissues. MATERIALS AND METHODS: Mandibular bilateral recipient
      sites in six Labrador dogs were established by extracting premolars and molars.
      After 3 months, two TPS (titanium plasma sprayed) implants and two SLA
      (sandblasted, large grit, acid etched) implants were placed on each side of the
      mandible in each dog. Three implants were lost in the initial healing phase,
      leaving 45 implants for evaluation. Following 6 months of healing, gold crowns
      were placed on implants on the test side of the mandible. The crowns were in
      supra-occlusal contact with the opposing teeth in order to create excessive
      occlusal load. Implants on the control side were not loaded. Plaque control was
      performed throughout the experimental period. Clinical measurements and
      standardised radiographs were obtained at baseline and 1, 3 and 8 months after
      loading. At 8 months, the dogs were killed and histologic analyses were
      performed. RESULTS: At 8 months, all implants were osseointegrated. The mean
      probing depth was 2.5+/-0.3 and 2.6+/-0.3 mm at unloaded and loaded implants,
      respectively. Radiographically, the mean distance from the implant shoulder to
      the marginal bone level was 3.6+/-0.4 mm in the control group and 3.7+/-0.2 mm in
      the test group. Control and test groups were compared using paired non-parametric
      analyses. There were no statistically significant changes for any of the
      parameters from baseline to 8 months in the loaded and unloaded implants.
      Histologic evaluation showed a mean mineralised bone-to-implant contact of 73% in
      the control implants and 74% in the test implants, with no statistically
      significant difference between test and control implants. CONCLUSION: In the
      presence of peri-implant mucosal health, a period of 8 months of excessive
      occlusal load on titanium implants did not result in loss of osseointegration or
      marginal bone loss when compared with non-loaded implants.

PMID- 15142088
TI  - Single-tooth replacement by immediate implant and connective tissue graft: a 1-9
      year clinical evaluation.
AB  - OBJECTIVES: The aim of the present study was to evaluate the long-lasting
      efficacy of a combined surgical protocol, using immediate implant and
      subepithelial connective tissue graft for single-tooth replacement. The
      advantages of this single-center, longitudinal, randomized, blind examiner
      research were the following: preservation of both keratinized mucosa amount and
      bone tissue, optimal peri-implant marginal sealing, satisfactory aesthetic
      results, reduction in treatment time. MATERIALS AND METHODS: In the time period
      from 1990 to 1998, 116 patients were consecutively admitted for treatment with a
      total of 116 solid screw ITI-implants supporting single crowns. Ninety-six
      patients underwent the proposed combined treatment (test group), while 20
      received only single immediate implants (control group). The observation time
      extended from 1 up to 9 years. RESULTS: The 9-year cumulative survival rate was
      100% for both test and control groups. Comparative statistical analysis of soft
      and hard tissue peri-implant parameters demonstrated better results in the test
      group than in the control during every single 3-year analysis and especially in
      the last observation interval. The test group also showed very good results in
      terms of aesthetic parameters, which estimated the keratinized mucosa width, the
      alignment of crown emergence profile and the patient's satisfaction. CONCLUSION:
      Single-tooth replacement by immediate solid screw ITI implants in association
      with connective tissue autograft was demonstrated to be a predictable procedure.
      Moreover, this treatment can be considered as a sure system to reach an excellent
      functional and harmonious aesthetic restoration.

PMID- 15142089
TI  - Immediate occlusal loading of Osseotite implants in the lower edentulous jaw. A
      multicenter prospective study.
AB  - OBJECTIVE: This paper reports the results of a prospective multicenter clinical
      study on immediately fully occlusally loaded full-arch screw-retained prostheses
      with distal extensions (hybrid prostheses) supported by Osseotite implants
      inserted in edentulous lower jaws. METHOD AND MATERIAL: Sixty-two patients were
      enrolled in four clinical centers. Three hundred and twenty-five Osseotite
      implants were inserted and occlusally loaded according to an immediate loading
      protocol. The temporary prosthesis was delivered 4 h from surgery. The final
      prosthesis was delivered after 6 months. Marginal bone loss was monitored from
      periapical radiographs using a computerized technique. RESULTS: Two implants
      failed to integrate within 2 months of occlusal loading. A cumulative implant
      success rate of 99.4% was achieved for a period of 12-60 months postplacement
      (mean 28.6+/-14.1 (SD) months). Crestal bone loss around the immediately loaded
      implants was similar to that reported for standard delayed loading protocols.
      CONCLUSION: The results of this study suggest that the rehabilitation of the
      edentulous mandible by an immediate occlusally loaded hybrid prosthesis supported
      by five to six Osseotite implants represents a viable alternative treatment to
      classic delayed loading protocols.

PMID- 15142091
TI  - Effects of cortical bone perforation on experimental guided bone regeneration.
AB  - This study was designed to evaluate the effects of cortical bone perforation
      histologically and histomorphometrically on guided bone regeneration (GBR) in
      rabbits. After elimination of the periosteum, cortical bone defects of two sizes
      were made in the external cortical plate of the frontal bone (Group A: 1 x 15 mm;
      Group B: 3 x 15 mm). A non-resorbable membrane filled with autogenous blood was
      placed in the experimental area and secured with titanium pins. After 1 and 2
      weeks, vascularized connective tissue and new bone were generated in the space
      surrounding the defects in both the groups. The amount of vascularized connective
      tissue generated in Group B was greater than that in Group A at 1 week. Alkaline
      phosphatase (ALP) was expressed on the bone surrounding the perforation. The
      expression of ALP was more extensive in Group B than in Group A and was
      proportional to the breadth of perforation. At 2 weeks, the perforated region was
      almost covered with new bone in Group A. ALP was expressed at the periphery of
      newly formed bone. The expression of ALP was proportional to the breadth and
      height of perforation. At 6 weeks, semicircular outgrowth of bone towards the
      periphery of the perforated region was observed in both the groups. Newly formed
      bone volume and ALP expression in Group B were more extensive than those in Group
      A. At 12 weeks, the space was filled with bone and connective tissue in both the
      groups. There was no difference in ALP expression between Groups A and B.
      Histomorphometric analysis showed significant differences between both the groups
      (two-way ANOVA, P<0.01). We conclude that a larger perforation is associated with
      prompter bone formation in the secluded space during GBR.

PMID- 15142090
TI  - The influence of a biomaterial on the closure of a marginal hard tissue defect
      adjacent to implants. An experimental study in the dog.
AB  - OBJECTIVES: The present experiment was performed to determine the influence of
      Bio-Oss on hard tissue formation at sites that, following implant installation,
      presented a 1-1.25 mm wide marginal defect. MATERIAL AND METHODS: Four Labrador
      dogs were used. The premolars and first molars on both sides of the mandible were
      extracted. After 3 months, mucoperiosteal flaps were elevated and three
      experimental sites were prepared for implant installation in each side of the
      mandible. A step drill was used to widen the marginal 5 mm of the canal. Thus,
      following the placement of the implant (3.3 x 10 mm, SLA surface, Straumann AG,
      Waldenburg, Switzerland) a circumferential gap, about 1-1.25 wide and 5 mm deep,
      remained lateral to the titanium rod. The test sites in the left side of the
      mandible were first filled with a deproteinized cancellous bone mineral (Bio
      Oss). The defect sites in the right side of the mandible (control sites) were
      left for spontaneous healing. A resorbable barrier membrane (Bio-Gide) was placed
      to cover the implant and the bone tissue in two sites of each quadrant, while the
      third site was left without membrane placement. The flaps were repositioned to
      cover all defect sites and were sutured. After 4 months of healing, block
      biopsies of each implant site were dissected and processed for ground sectioning.
      RESULTS: It was demonstrated that at 4 months, all types of defects were filled
      with newly formed bone and that the biomaterial placed in the marginal defect in
      conjunction with implant installation during healing became incorporated in the
      newly formed bone tissue. A high degree of contact was established between the
      Bio-Oss particles and the newly formed bone. CONCLUSION: Bio-Oss became
      integrated with the newly formed bone. In the model used, Bio-Oss did not enhance
      the process of bone formation and defect closure.

PMID- 15142092
TI  - Effects of fibrin sealant protein concentrate with and without platelet-released
      growth factors on bony healing of cortical mandibular defects. An experimental
      study in minipigs.
AB  - In this study, the effects of fibrin sealant protein concentrate (FSPC; from the
      Tissucol Kit, Baxter, Vienna, Austria) with and without platelet-released growth
      factors (PRGF) on bony healing of cortical mandibular defects were investigated.
      Defects made in the facial mandibular wall of eight adult minipigs with a hollow
      drill were filled with FSPC alone, a mix of FSPC+PRGF or left untreated as
      controls. The animals were killed 4 and 8 weeks later. Specimens were processed
      for histology with the Donath method (1988) and stained with the Levai-Laczko
      stain. On histology, periosteal osteoneogenesis exceeded endosteal bone
      formation. No difference was seen in bone formation between FSPC alone, FSPC+PRGF
      and the controls at 4 and 8 weeks. On histomorphometry, there was no significant
      difference between the three groups in terms of the percent of newly formed bone
      at 4 and 8 weeks (P=0.6977). This study showed that FSPC neither increased nor
      decreased the amount of newly formed bone vs. controls and that the addition of
      PRGF had no effects on bone regeneration of cortical minipig bone at 4 and 8
      weeks.

PMID- 15142094
TI  - A histological evaluation of the involvement of Bio-Oss in osteoblastic
      differentiation and matrix synthesis.
AB  - This study was designed to investigate the responses of bone cells to a
      deproteinized bovine bone material, Bio-Oss (Geistlich-Pharma, Wolhunsen,
      Switzerland), which was grafted in artificial bone defects of rat femurs.
      Standardized bone defects in the cortical bone of the right femurs were grafted
      with Bio-Oss particles. Narrow penetrations were prepared on the bottom of the
      cavity, enabling osteogenic cells to migrate from the bone marrow. A defect in
      the left femur without Bio-Oss was used as a control. The treated femurs were
      histochemically examined at 1, 3, 5, 7, and 14 days after the operation. At day
      1, no osteogenic migration into the cavities occurred in either the control or
      experimental groups. At day 3, alkaline phosphatase (ALPase) immunohistochemistry
      showed a migration of the positive cells at the bottom of the cavities of the
      experimental groups, but not in the control ones. At day 5, new bone formation
      was recognized at the bottom of the cavity of both groups. In the experimental
      group, ALPase-positive cells were localized on Bio-Oss and/or on the thin bone
      matrix that covered this material. The superficial layer of Bio-Oss underlying
      the newly formed bone exhibited osteocalcin immunoreactivity. Transmission
      electron microscopy revealed osteoblasts depositing bone matrices--including
      collagen fibers--on the surface of Bio-Oss. At days 7 and 14, woven bone occupied
      the previous cavities of both control and experimental groups, accompanied by
      osteoclasts. Thus, Bio-Oss appears to serve as a scaffold for osteogenic cells as
      well as to promote osteoblastic differentiation and matrix synthesis.

PMID- 15142093
TI  - Enhancement of bone volume in guided bone augmentation by cell transplants
      derived from periosteum: an experimental study in rabbit calvarium bone.
AB  - Bone morphology is genetically encoded and it is usually difficult to change its
      structure without invasive surgery. We have tried to stimulate bone augmentation
      by a combination of guided bone regeneration techniques and cell transplants with
      collagen scaffolds for the suitable skeletal framework. In vitro-expanded tibia
      periosteum cells were used to promote osteogenesis with collagen scaffolds and
      titanium (Ti) or poly-L-lactic acid (PLLA) caps as barriers to create a space
      facing connective tissue under calvarium skin. This approach was assessed in the
      defective skull bone of a rabbit model. After a 12-week healing period,
      histomorphometric analyses were performed to determine the percentage of newly
      formed mineralized tissue in the cap. The mean percentage of newly formed
      mineralized tissue within the cap was 15.4%+/-3.99 for the Ti cap group, 15.5%+/
      4 for the PLLA cap group, 6.19%+/-4.94 for the PLLA cap+collagen carrier group
      and 23.1%+/-23.1 for the PLLA+collagen carrier+cell transplants group. The cell
      transplant group showed a significantly higher value than other groups (P<0.05,
      Wilcoxon signed rank test, Mann-Whitney U-test). This approach of guided bone
      augmentation and cultured cell transplants with collagen carrier exhibited
      significantly greater morphogenesis of mineralized tissue than the control over a
      12-week experimental period.

PMID- 15142095
TI  - Low-level laser therapy stimulates bone-implant interaction: an experimental
      study in rabbits.
AB  - The aim of the present study was to investigate the effect of low-level laser
      therapy (LLLT) with a gallium-aluminium-arsenide (GaAlAs) diode laser device on
      titanium implant healing and attachment in bone. This study was performed as an
      animal trial of 8 weeks duration with a blinded, placebo-controlled design. Two
      coin-shaped titanium implants with a diameter of 6.25 mm and a height of 1.95 mm
      were implanted into cortical bone in each proximal tibia of twelve New Zealand
      white female rabbits (n=48). The animals were randomly divided into irradiated
      and control groups. The LLLT was used immediately after surgery and carried out
      daily for 10 consecutive days. The animals were killed after 8 weeks of healing.
      The mechanical strength of the attachment between the bone and 44 titanium
      implants was evaluated using a tensile pullout test. Histomorphometrical analysis
      of the four implants left in place from four rabbits was then performed. Energy
      dispersive X-ray microanalysis was applied for analyses of calcium and phosphorus
      on the implant test surface after the tensile test. The mean tensile forces,
      measured in Newton, of the irradiated implants and controls were 14.35 (SD+/
      4.98) and 10.27 (SD+/-4.38), respectively, suggesting a gain in functional
      attachment at 8 weeks following LLLT (P=0.013). The histomorphometrical
      evaluation suggested that the irradiated group had more bone-to-implant contact
      than the controls. The weight percentages of calcium and phosphorus were
      significantly higher in the irradiated group when compared to the controls
      (P=0.037) and (P=0.034), respectively, suggesting that bone maturation processed
      faster in irradiated bone. These findings suggest that LLLT might have a
      favourable effect on healing and attachment of titanium implants.

PMID- 15142096
TI  - Problems related to an intraoral approach for experimental surgery on minipigs.
AB  - The purpose of the present study was to compare block and particulated bone
      grafts for jaw augmentation in combination with immediate implant placement. Bone
      defects measuring 10 mm x 10 mm x 30 mm were prepared on each side of the
      mandible of eight minipigs. After a healing period of 3 months, the defects in
      four animals were augmented with iliac crest grafts as a block or particulated
      graft, combined with immediate implant insertion. Clinical inspection was
      performed after 14 days. Complete exposure of grafts and implants was discovered.
      The surgical procedures were altered in the fifth animal. Inspection was made
      after 4 days showing no alterations. However, after another 7 days, grafts and
      implants were exposed. Consequently, the study was discontinued and all eight
      animals were killed. It is concluded that an intraoral approach is not applicable
      for this type of experimental surgery in minipigs. This paper describes some of
      the presumed reasons for the failure of the study.

PMID- 15142097
TI  - A clinical long-term radiographic evaluation of graft height changes after
      maxillary sinus floor augmentation with a 2:1 autogenous bone/xenograft mixture
      and simultaneous placement of dental implants.
AB  - The aim of the present study was to assess long-term changes in sinus-graft
      height after maxillary sinus floor augmentation and simultaneous placement of
      implants. A total of 191 patients who underwent maxillary sinus floor
      augmentation were radiographically followed for up to about 10 years. A 2 : 1
      mixture of autogenous bone and bovine xenograft (Bio-Oss) was used as the graft
      material. Sinus-graft height was measured using 294 panoramic images immediately
      after augmentation and up to 108 months subsequently. Changes in sinus-graft
      height were calculated with respect to implant length and original sinus height.
      Patients were divided into three groups based on the height of the grafted sinus
      floor relative to the implant apex: Group I, in which the grafted sinus floor was
      above the implant apex; Group II, in which the implant apex was level with the
      grafted sinus floor; and Group III, in which the grafted sinus floor was below
      the implant apex. After augmentation, the grafted sinus floor was consistently
      located above the implant apex. After 2-3 years, the grafted sinus floor was
      level with or slightly below the implant apex. This relationship was maintained
      over the long term. Sinus-graft height decreased significantly and approached
      original sinus height. The proportion of patients classified as belonging to
      Group III reached a maximum from year 3 onwards. The clinical survival rate of
      implants was 94.2%. All implant losses occurred within 3 years after
      augmentation. We conclude that progressive sinus pneumatization occurs after
      augmentation with a 2 : 1 autogenous bone/xenograft mixture, and long-term
      stability of sinus-graft height represents an important factor for implant
      success.

PMID- 15142098
TI  - Simvastatin promotes osteogenesis around titanium implants.
AB  - OBJECTIVES: Hydroxymethylglutaryl-coenzyme A reductase inhibitors, the so-called
      statins, have been widely used for hyperlipidemic patients, and it was recently
      reported that it promoted bone formation. In the present study, we examined the
      effect of simvastatin on the promotion of osteogenesis around titanium implants.
      MATERIALS AND METHODS: Ten 30-week-old rats received pure titanium implants in
      both tibiae, and were then divided into experimental and control groups. The
      experimental group was administered simvastatin daily. Thirty days later, all
      animals were killed and then specimens were prepared. The bone contact ratio
      (BCR) to the implant and bone density (BD) around the implant, as well as
      histological findings, were obtained. RESULTS: In the control group, newly formed
      bone could be seen around the implants. It was seen to be in direct contact with
      the implant surface, but otherwise unmineralized connective tissue was
      occasionally interposed. In the medullary canal, a scanty amount of bone
      trabeculae was observed. In the experimental group, in contrast, thicker bone
      trabeculae were abundantly seen in the medullary canal and showed a mesh-like
      structure. In the histometrical observations, both BCR and BD of the experimental
      group were significantly greater than those of the control group. CONCLUSION: The
      administration of simvastatin increases the value of both BCR and BD. This drug
      may have the potential to improve the nature of osseointegration.

PMID- 15142099
TI  - Implant-supported fixed prostheses in the edentulous maxilla. A 2-year clinical
      and radiological follow-up of treatment with non-submerged ITI implants.
AB  - OBJECTIVES: To evaluate the survival rate of non-submerged solid-screw ITI dental
      implants with a rough (titanium plasma sprayed, TPS) surface in the edentulous
      maxilla after 1 and 2 years of loading. MATERIAL AND METHOD: Twenty-five patients
      (mean age 64 years) with edentulous upper jaws received five-seven implants and,
      after a mean healing time of 6.9 months, screw-retained implant-supported fixed
      prostheses. A total of 146 ITI solid screw TPS implants were inserted. The
      diameter of 56% of the implants was smaller (3.3 mm) than the standard (4.1 mm)
      and the diameter of the rest (44%) was standard. The bone quantity of the
      majority of the patients was low and the bone quality poor. Clinical parameters
      were registered at baseline and at two annual follow-ups. Radiological
      examinations and assessments were also made at these times. RESULTS: Mean
      marginal bone level at baseline was measured at a point 4.52 mm (range 1.45-7.70,
      SD 1.2) apical of the reference point. Mean bone loss from baseline to 1 year of
      loading was 0.24 mm (SD 0.9, P=0.002) and from 1 year to 2 years of loading 0.15
      mm (SD 0.4, P<0.001). Five implants failed, four of which were early failures
      prior to loading. One implant failed shortly after bridge installation. The
      cumulative survival rate was 96.6% after 1 and 2 years. CONCLUSION: ITI TPS solid
      screw implants in combination with fixed prostheses had successful survival rates
      and were found to be a viable treatment alternative in the edentulous maxilla.

PMID- 15142100
TI  - The immediate rehabilitation by means of a ready-made final fixed prosthesis in
      the edentulous mandible: a 1-year follow-up study on 50 consecutive patients.
AB  - Although a two-stage procedure with symphyseal oral implants can lead to a long
      term (15 years) 99% cumulative survival rate, a one-stage approach with immediate
      loading via prefabricated elements seems to offer a short-term acceptable outcome
      with significantly lower costs. A series of 50 consecutive patients, not
      eliminated for any systemic or smoking condition, received at the department of
      periodontology three implants in the symphyseal area, connected by a very rigid
      horse shoe-shaped titanium bar. A final screw retained prosthetic framework was
      placed on top of it at the department of prosthetic dentistry within 2 days after
      surgery (44) or after a delay, due to purely external factors, of up to 10 days
      (6). Forty-five patients were followed for 1 year. In one patient, all three
      implants failed and another four patients were lost to follow-up. The cumulative
      failure rates for implants and prostheses at 1 year were, respectively, 7.3% and
      5%. The mean marginal bone loss at 1 year was 1.08 mm (SD: 1.62; range -5.68 to
      +2.55). This study shows that stable marginal bone levels can be maintained
      around immediately loaded implants in the lower jaw in an average patient
      population for at least 1 year. The survival rate is, however, lower than for a
      staged approach.

PMID- 15142101
TI  - Vertical distraction osteogenesis of the mandible applied to an iliac crest
      graft: report of a case.
AB  - OBJECTIVES: This clinical case represents a particular application of vertical
      distraction osteogenesis of the mandible. The surgical technique was applied to
      an iliac crest bone graft previously positioned on an anterior mandibular defect
      with the aim to restore the vertical height after a partial resorption in a
      trauma patient. CASE REPORT: Distraction osteogenesis was applied because it was
      necessary to restore the mandibular height in a young male patient who presented
      with a post-trauma anterior mandibular bony deficiency. Because of the
      irregularity of the mandibular surface and the depth of the defect, the patient
      first underwent an iliac crest bone grafting that, after 3 months, showed partial
      resorption. Vertical distraction osteogenesis was performed on the grafted
      mandible in order to obtain a satisfactory bony height of the mandibular ridge.
      Then the patient was successfully rehabilitated by means of an implant-supported
      prosthesis. CONCLUSION: Vertical distraction osteogenesis appears to be a
      versatile surgical procedure, which can be applied as a secondary treatment in
      patients presenting with mandibular trauma sequelae.

PMID- 15142102
TI  - Novel development for intraoral distraction osteogenesis by individually
      fabricated traction prostheses.
AB  - Modified fixed or removable partial dentures are used for intraoral distraction
      osteogenesis. These traction prostheses rest on teeth or endosseous implants and
      direct distraction forces to an endosseous implant in the osteotomy segment. This
      article explains the fabrication and function of custom-made traction prostheses
      for 1-, 2- and 3-dimensional distraction osteogenesis.

PMID- 15142103
TI  - Swallowing thresholds of mandibular implant-retained overdentures with variable
      portion sizes.
AB  - We analysed the effect of three portion sizes Optocal Plus (small, medium and
      large) on swallowing thresholds in subjects with either conventional complete
      dentures or mandibular implant-retained overdentures (transmandibular and
      permucosal cylindric implants). Tests were carried out in 52 women and 15 men
      (mean age 59 years) 4 years after treatment in a randomised controlled clinical
      trial. The results indicated that the degree of mucosal support for the
      mandibular denture did not affect the number of chewing strokes, time till
      swallowing or swallowed particle size. Only the chewing rate differed: subjects
      wearing mandibular implant-retained overdentures chewed the food at a higher rate
      than complete-denture wearers. With larger portion sizes, subjects needed
      significantly more chewing strokes and time until swallowing and they would have
      swallowed larger particles. Men chewed their food more efficiently than women, as
      they used the same number of chewing strokes and time, but achieved a greater
      particle size reduction at the swallowing moment.

PMID- 15142111
TI  - Spontaneous intramural intestinal haemorrhage in a haemophiliac patient.

PMID- 15142112
TI  - Interstitial pneumonitis during imatinib therapy.

PMID- 15142113
TI  - Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia.
AB  - Present day paediatric co-operative group acute lymphoblastic leukaemia (ALL)
      protocols cure approximately 80% of patients, a result achieved largely through
      the use of risk-stratified therapies that employ multiple chemotherapy agents.
      These risk-based therapies utilize host and leukaemia traits to select the most
      appropriate therapy. However, these risk-stratified approaches predict therapy
      response imperfectly and an important fraction of patients experience relapse or
      therapy-related toxicity. Pharmacogenetics, the study of genetic variations in
      drug-processing genes and individual responses to drugs, may enable the improved
      identification of patients at higher risk for either disease relapse or
      chemotherapy-associated side effects. While the impact of genetic variation in
      the thiopurine-S-methyltransferase gene on ALL treatment outcome and toxicity has
      been extensively studied, the role of other polymorphisms remains less well
      known. This review summarizes current research on the impact of genetic variation
      in drug-processing genes in paediatric ALL and reviews important methodological
      and statistical issues presently challenging the field of pharmacogenetics.

PMID- 15142114
TI  - Chronic graft versus host disease.
AB  - The ability to cure increasing numbers of individuals for malignant and non
      malignant diseases with the use of stem cell transplantation has resulted in a
      growing number of long-term survivors with unique medical issues. Chronic graft
      versus host disease (GvHD) continues to be a significant problem in the
      allogeneic stem cell transplant setting and, as we continue to use alternative
      stem cell sources and attempt to modulate the immune system to increase an anti
      tumour effect, we will probably see rising numbers of patients with this
      complication. The capacity to treat this problem and improve both the immediate
      quality of life as well as long-term effects is imperative and requires the
      ability of haematologists/oncologists to identify chronic GvHD and its multi
      organ system presentations. We describe the risk factors for developing chronic
      GvHD, its presentation and the current treatment options for both initial therapy
      and secondary treatment.

PMID- 15142115
TI  - Strong impact of highly active antiretroviral therapy on survival in patients
      with human immunodeficiency virus-associated Hodgkin's disease.
AB  - Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome
      (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected
      patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD)
      with respect to the use and efficacy of highly active antiretroviral therapy
      (HAART) and other prognostic factors. To evaluate the effects of several
      variables on overall survival (OS), Kaplan-Meier statistics and extended Cox
      regression analysis were performed. Response to HAART was used as a time
      dependent variable and was defined as an increase of >0.1 x 10(9) CD4 cells/l
      and/or at least one viral load <500 copies/ml during the first 2 years following
      diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and
      2002 were included in the study. In the Cox model, the only factors independently
      associated with OS were HAART response [relative hazard (RH) 0.19; 95% confidence
      interval (CI) 0.06-0.60], complete remission (RH 0.30, 95% CI 0.13-0.72), and age
      <or=45 years (RH 0.23; 95% CI 0.09-0.60). Median survival time in patients
      without HAART response was 18.6 months, whereas the median survival time in
      patients with HAART response was not reached (89% OS at 24 months). In this
      cohort, a significant improvement in survival was found in patients with HIV-HD
      who responded to HAART.

PMID- 15142116
TI  - FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological
      associations and prognostic impact.
AB  - FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a
      mutation at the activation-loop position 835, D835, are common in acute
      promyelocytic leukaemia (APL). We investigated the clinicopathological
      associations and prognostic impact of FLT-3 aberrations in a cohort of APL
      patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction
      (PCR), and the ITD was recognized as an increase in the size of the PCR product.
      FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV
      site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were
      detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835
      mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated
      with higher presentation white blood cell count (WBC) and microgranular
      morphology. Early/induction deaths were related to male sex and high presentation
      WBC. There was a trend for FLT-3 ITD to be associated with non-remission (P =
      0.06). For disease-free survival, high WBC was the only significant adverse
      factor. Male sex, high WBC and FLT-3 ITD were significant adverse factors for
      overall survival. These findings have important implications on the possible use
      of FLT-3 inhibitors in the treatment of APL.

PMID- 15142117
TI  - Phase 2 study of arsenic trioxide in patients with relapsed or refractory
      multiple myeloma.
AB  - Despite aggressive and innovative therapy, patients with multiple myeloma (MM)
      invariably relapse and die of their disease. New options for non-cytotoxic
      salvage therapy and additional therapeutic strategies are needed. Arsenic
      trioxide, an antitumour agent with a multifaceted mechanism of action, induces
      apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients
      and, in preliminary studies, displayed clinical activity in patients with late
      stage MM. A phase 2, multicentre, open-label study of arsenic trioxide was
      conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior
      therapy. Patients received arsenic trioxide 0.25 mg/kg/d for 5 d/week during the
      first 2 weeks of each 4-week cycle. Sixteen patients had grade 3 or 4 neutropenia
      and one required antibiotics. Reductions (25% or more) in serum M-protein levels
      occurred in eight of 24 (33%) patients. An additional six (25%) patients had
      stable disease. The median time to response was 67.5 d, with a median duration of
      response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in
      two patients with high baseline values. These data indicate that arsenic trioxide
      is active and reasonably well tolerated as a single-agent salvage therapy, even
      in patients with late-stage, relapsed and refractory MM.

PMID- 15142118
TI  - A sensitive model for prediction of relapse in adult acute myeloid leukaemia with
      t(8;21) using white blood cell count, CD56 and MDR1 gene expression at diagnosis.
AB  - Acute myeloid leukaemia (AML) carrying t(8;21) has an overall favourable
      prognosis. However, relapse occurs and the impact of multidrug resistance gene
      (MDR1) expression on recurring disease in this group of patients is not known. We
      determined quantifiable MDR1 expression in the bone marrow of 28 AML patients
      with t(8;21) by a validated real-time polymerase chain reaction assay. Using MDR1
      expression, white blood cell count and CD56 expression at diagnosis we observed
      complete concordance of predicted and observed relapses. A calculated logit out
      of these three variables was a strong independent prognostic factor for overall
      (P = 0.007) and disease-free survival (P = 0.002).

PMID- 15142119
TI  - Comparative analysis of clinical outcomes after allogeneic bone marrow
      transplantation versus peripheral blood stem cell transplantation from a related
      donor in Japanese patients.
AB  - A reduced incidence of graft versus host disease (GvHD) has been documented among
      Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese
      are genetically more homogeneous than western populations. To clarify whether
      this ethnic difference affects the results of allogeneic peripheral blood stem
      cell transplantation (PBSCT), we conducted a nationwide survey to compare
      clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human
      leucocyte antigen-identical-related donor in Japanese patients. The cumulative
      incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The
      cumulative incidence of extensive chronic GvHD at 1 year was significantly higher
      after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of
      GvHD were different between the two groups. By multivariate analyses, the
      incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem
      cell source did not affect the incidence of acute GvHD, transplant-related
      mortality, relapse or survival. We concluded that Japanese PBSCT patients have an
      increased risk of chronic GvHD compared with BMT patients, but the incidence of
      acute GvHD was still lower than in western populations. Thus, the choice of
      haematopoietic stem cell source should be considered based on data for individual
      ethnic populations.

PMID- 15142120
TI  - Prophylactic effect of recombinant factor VIIa in factor VII deficient patients.
AB  - Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder
      associated with a bleeding tendency. We describe three patients with congenital
      FVII deficiency who have been treated with activated recombinant factor VII
      (rVIIa). Two patients had novel mutations and were treated prophylactically with
      1.2 mg rVIIa two to three times a week. Patients 1 and 2 had a severe bleeding
      tendency. The frequency and severity of bleeding decreased by treatment with
      rVIIa compared with similar treatment with plasma-derived FVII. The third patient
      with a moderate bleeding phenotype was treated on demand and showed no change in
      the frequency of bleeding upon treatment with rVIIa or plasma products. The
      beneficial effect of rVIIa cannot be explained by the rVIIa half-lives.
      Pharmacokinetical analysis showed rVIIa activity half-lives of 35, 50 and 54 min
      for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of
      FVII deficient patients with rVIIa appears to be applicable, safe and successful,
      although the mechanism of action remains to be elucidated.

PMID- 15142121
TI  - Phosphatidylinositol-3 kinase inhibitors reproduce the selective
      antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor
      cells.
AB  - We investigated the role of the phosphatidylinositol-3 kinase (PI-3K) pathway in
      regulating the proliferation of primary chronic myeloid leukaemia (CML)
      progenitor cells by using imatinib to inhibit the activity of p210(Bcr-Abl). The
      effect of imatinib on the expression of PI-3K pathway proteins was investigated
      by kinase assays and Western blotting; PI-3K was inhibited by wortmannin or
      LY294002, Jak2 by AG490 and farnesylation by FTI II; progenitor cell
      proliferation (self-renewal) was measured by growing myeloid colonies in vitro,
      then replating them to observe secondary colony formation. Suppression of
      p210(Bcr-Abl) with imatinib indirectly suppressed the activity of PI-3K and its
      downstream targets (Erk, Akt and p70S6 kinase), thereby implicating the PI-3K
      pathway in p210(Bcr-Abl)-mediated signalling in primary CML progenitor cells. The
      PI-3K inhibitors, wortmannin and LY294002 reproduced the differential effects of
      imatinib on normal and CML progenitor cell proliferation in vitro by increasing
      normal cell (P = 0.001) and reducing CML cell proliferation (P = 0.0003). This
      differential effect was attributable to dysregulated signalling by granulocyte
      colony-stimulating factor in CML. The responses of individual patient's cells to
      wortmannin correlated with their responses to imatinib (P = 0.004) but not their
      responses to AG490 (Jak2 kinase inhibitor) or FTI II (farnesyltransferase
      inhibitor). Individual responses to wortmannin also correlated with responses to
      interferon alpha (IFNalpha) (P = 0.016). Imatinib-resistant K562 cells were
      sensitive to LY294002. Inhibition of the PI-3K pathway may be common to imatinib
      and IFNalpha and reflect dysregulated cytokine signalling. As imatinib-resistant
      cells remained sensitive to wortmannin and LY294002, targeting the PI-3K pathway
      may provide an alternative therapy for imatinib-resistant patients.

PMID- 15142122
TI  - Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection
      against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase
      signalling pathway.
AB  - Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined
      the effects of hydrogen peroxide (H(2)O(2)) on arsenic trioxide (As(2)O(3))
      induced cell killing. Low concentrations of H(2)O(2) (200 micromol/l) inhibited
      the ability of As(2)O(3) to induce apoptosis in the Burkitt's lymphoma cell line
      Raji. H(2)O(2) altered the form of cell death from apoptosis to pyknosis/necrosis
      and also lowered the degree of cell killing by As(2)O(3). H(2)O(2) was capable of
      preventing caspase-3 activation induced by As(2)O(3) in Raji cells. Incubation of
      cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100
      nmol/l), blocked the effects of H(2)O(2) on As(2)O(3)-induced caspase-3
      activation. In addition, the PI-3K inhibitor partially blocked the effects of
      H(2)O(2) on up-regulation of Bcl-2 and Bcl-X(L) protein expression, down
      regulation of Bax protein expression, and phosphorylation of Bcl-2 and
      IkappaBalpha. This investigation demonstrated for the first time that low
      concentrations of H(2)O(2) provide protection against the in vivo of As(2)O(3)
      induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during
      H(2)O(2), inhibiting As(2)O(3)-induced apoptosis in the Burkitt's lymphoma cells.
      As(2)O(3)-induced cancer cell apoptosis may be enhanced by certain antioxidants
      in the treatment protocol.

PMID- 15142123
TI  - Four pedigrees of the cation-leaky hereditary stomatocytosis class presenting
      with pseudohyperkalaemia. Novel profile of temperature dependence of Na+-K+ leak
      in a xerocytic form.
AB  - We report four pedigrees of the group of Na(+)-K(+)-leaky red cell disorders of
      the 'hereditary stomatocytosis' class. Each showed pseudohyperkalaemia because of
      temperature-dependent loss of K(+) from red cells on storage of whole blood at
      room temperature. All pedigrees showed an abnormality in the temperature
      dependence of the 'passive leak' of the membrane to K(+). Two pedigrees, both of
      which showed a compensated haemolytic state with dehydrated red cells and target
      cells on the blood film, showed a novel pattern, in which the profile was flat
      between 37 degrees C and about 32 degrees C then dropped as the temperature was
      reduced to zero. The third showed the 'shallow slope' profile, with stomatocytes
      on the blood film and very markedly abnormal intracellular Na(+) and K(+) levels.
      Minimal haemolysis was present. The fourth pedigree, of Asian origin, showed the
      shoulder pattern (minimum at 32 degrees C, maximum at 12 degrees C) with
      essentially normal haematology. Both of these latter two forms have previously
      been seen in other pedigrees. The first variant represents a novel kind of
      temperature dependence of the passive leak found in these pedigrees presenting
      with pseudohyperkalaemia.

PMID- 15142124
TI  - Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood
      group system and collection.
AB  - The aim of this study was to further explore the molecular genetic bases of the
      clinically important but rare blood group phenotypes p, P(1) (k) and P(2) (k) by
      analysis of the 4-alpha-galactosyltransferase (P(k)) and 3-beta-N
      acetylgalactosaminyltransferase (P) genes responsible for synthesis of the
      related P(k) (Gb(3)) and P (Gb(4)) antigens respectively. Lack of these
      glycolipid moieties is associated with severe transfusion reactions and recurrent
      spontaneous abortions but also offers immunity against certain infectious agents.
      Blood samples from 20 p and 11 P(1) (k) or P(2) (k) individuals of different
      geographic and ethnic origin were investigated. DNA sequencing by capillary
      electrophoresis was performed following amplification of the coding regions in
      the P(k) or P genes. In the P(k) gene, nine novel and five previously described
      mutations were detected. One of the newly found mutations introduced an immediate
      stop, five shifted the reading frame introducing premature stop codons and three
      were missense mutations causing amino acid substitutions in conserved regions of
      the transferase. Four new and two previously described mutations in the P gene
      were found. Three of the novel alleles reported here carried nonsense mutations
      whilst the fourth allele had a missense mutation. The finding of 13 novel
      mutations in 14 alleles emphasizes further the genetic heterogeneity at the
      glycosyltransferase loci underlying the GLOB blood group system and collection.

PMID- 15142125
TI  - Erythropoietin receptor defect: a cause of primary polycythaemia.

PMID- 15142126
TI  - Bone marrow examination in obese patients.

PMID- 15142130
TI  - Genes differentially expressed in prostate cancer.
AB  - Because of the heterogeneity of prostate cancer knowledge about the genes
      involved in prostate carcinogenesis is still very limited. Previously, the use of
      novel high-throughput technologies offered the possibility to investigate broad
      gene expression profiles and thus helped to improve understanding of the
      molecular basis of prostate disease. Many candidate genes have been identified so
      far which have a more or less strong effect on prostate cancer. This vast number
      of gene expression changes show that it is unlikely that only one gene promotes
      prostate cancer. Conversely, it seems more likely that a broad network of
      molecular changes is involved in the complex cascade of events which lead to
      tumour formation and progression, respectively. A few of these novel molecular
      targets are currently under clinical evaluation. This paper gives an overview of
      several interesting candidate genes which may be useful as improved biomarkers
      for diagnosis or as targets for developing novel treatment methods.

PMID- 15142131
TI  - Women's sexual dysfunction: a pathophysiological review.

PMID- 15142129
TI  - Diet, anthropometric measures and prostate cancer risk: a review of prospective
      cohort and intervention studies.
AB  - We reviewed 37 prospective cohort and four intervention studies on potential
      dietary risk factors for prostate cancer, published between 1966 and September
      2003. Some studies were limited by small size, crude measurement of dietary
      exposure and limited control for confounders. Intervention and prospective cohort
      studies support a protective role against prostate cancer for selenium, and
      possibly for vitamin E, pulses and tomatoes/lycopene. Overall consumption of
      meat, eggs, vegetables, fruit, coffee, tea, carotenoids and vitamins A, C and D
      was not consistently related to prostate cancer risk. Intervention studies also
      indicate that supplementation with beta-carotene does not lower prostate cancer
      risk, except possibly in men with low beta-carotene status at baseline. For
      specific types of meat, alcoholic drinks, dairy products, fat and anthropometric
      measures, most cohort studies suggest either an increased risk or no relation
      with prostate cancer. For calcium, two cohort studies suggest an increased risk
      at very high calcium intakes (>2000 mg/day). In conclusion, prospective studies
      are consistent with a protective role for selenium, and possibly vitamin E,
      pulses and tomatoes/lycopene, in the aetiology of prostate cancer. Studies are
      inconclusive on the role of meat, dairy products, fat, vegetables, fruits,
      alcohol and anthropometric measures, whereas a very high calcium intake appears
      to be positively associated with prostate cancer risk.

PMID- 15142132
TI  - Renal trauma: indications for imaging and surgical exploration.

PMID- 15142133
TI  - Training and mentoring in urology: the 'LAP' generation.

PMID- 15142134
TI  - Two-drug therapy is best for symptomatic prostate enlargement: could a
      combination of doxazosin and finasteride change clinical practice?

PMID- 15142135
TI  - Cognitive effects of hormonal treatment for prostate cancer.

PMID- 15142136
TI  - Early rehabilitation of erectile function after nerve-sparing radical
      prostatectomy: what is the evidence?

PMID- 15142137
TI  - Diet and prostate cancer.
AB  - There are four mini-reviews in this section, all on different areas of urological
      interest. Diet and prostate cancer continues to offer areas of clinical and
      laboratory research for investigation. Not every urologist looks after patients
      with spinal cord injury, but neuropathic bladder problems caused by other
      conditions are common. One of the acute conditions in these patients is autonomic
      dysreflexia, and this is covered here. I am about to introduce a series of papers
      which will form a consensus on the management of genitourinary trauma, which
      appears elsewhere in the journal. In this section this month, authors from
      Germany describe the diagnosis and treatment of male genital injuries. Finally,
      the concept that the urologists who operate on the largest volume of cases have
      the best outcomes from a particular operation is examined.

PMID- 15142138
TI  - The importance of autonomic dysreflexia to the urologist.

PMID- 15142139
TI  - Male genital injury: diagnostics and treatment.
AB  - This article reviews the current status of information on external male genital
      injuries, focusing on cause, diagnostic and therapeutic management of this
      uncommon entity. Because of the high risk of infection and the major importance
      of preserving fertility, male genital injuries represent a serious urological
      disorder that demands immediate urological treatment. The diagnostic procedure
      classically consists of taking a history and inspecting the wound; this provides
      enough diagnostic information for the correct choice of conservative or surgical
      treatment. In most cases open injuries of the genitalia require surgical
      exploration to determine the extent of possible scrotal, testicular, epididymal,
      cavernosal or urethral damage, to debride nonviable superficial or deep tissue,
      to drain existing haematomas or to control active bleeding. Furthermore, the
      correct therapeutic approach is crucial for preserving fertility and penile
      erection. In cases where bilateral ablation is necessary, measures to preserve
      sperm, e.g. testicular or microsurgical sperm extraction, or squeezing the ductus
      during orchidectomy, must be considered.

PMID- 15142140
TI  - The relationship between volume and outcome in urological surgery.

PMID- 15142141
TI  - Evaluation and management of renal injuries: consensus statement of the renal
      trauma subcommittee.
AB  - OBJECTIVE: To determine the optimal evaluation and management of renal injuries
      by review of the world's English-language literature on the subject. METHODS: A
      consensus conference convened by the World Health Organization and the Societe
      Internationale d'Urologie met to critically review reports of the diagnosis and
      treatment of renal trauma. The English-language literature about renal trauma was
      identified using Medline, and additional cited works not detected in the initial
      search obtained. Evidence-based recommendations for the diagnosis and management
      of renal trauma were made with reference to a five-point scale. RESULTS: There
      were many Level 3 and 4 citations, few Level 2, and one Level 1 which supported
      clinical practice patterns. Findings of nearly 200 reviewed citations are
      summarized. CONCLUSIONS: Published reports on renal trauma still rely heavily on
      expert opinion and single-institution retrospective case series. Prospective
      trials of the most significant issues, when possible, might improve the quality
      of evidence that dictates the behaviour of practitioners.

PMID- 15142142
TI  - Prevalence and patterns of self-initiated nutritional supplementation in men at
      high risk of prostate cancer.
AB  - OBJECTIVE: To define the prevalence and patterns of self-initiated herbal and
      vitamin supplementation among men at high risk of developing prostate cancer, as
      there is increasing public awareness of prostate cancer screening, risk-factor
      assessment and prevention, leading to increasing interest in the use and
      systematic study of nutritional therapies for prostate cancer prevention.
      SUBJECTS AND METHODS: Since 1996 our institution has prospectively maintained a
      prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program
      (PRAP). Eligibility includes African-American men, any man with at least one
      first-degree relative or two or more second-degree relatives with prostate
      cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self
      administered questionnaire was completed and included the use of nutritional
      supplements and complementary therapies. We divided men into groups who used
      supplements to lessen their cancer risk and those who did not. The prevalence and
      patterns of use were evaluated and the two groups then compared for differences
      in demographic, socio-economic and risk-perception variables. RESULTS: In all,
      345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use
      of dietary or herbal supplements were available on 333 men (97%), of whom over
      half (170) reported taking one or more supplements to prevent prostate cancer.
      Supplement use was divided into eight categories, including vitamins, minerals,
      extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots,
      or animal products. Most commonly used for self-initiated chemoprevention were
      vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a
      quarter of men (27%) took three or more agents. Men taking proactive preventative
      measures were statistically more likely to be Caucasian and aged > 60 years (P <
      0.05). African-Americans were less likely to self-initiate preventative steps.
      Men taking supplements tended to return more often for follow-up and participate
      in PRAP longer, while those not taking supplements tended to earn less and report
      less self-perceived risk. CONCLUSIONS: A significant proportion of men at risk of
      developing prostate cancer initiate measures they perceive to reduce their risk.
      Although the chemopreventative efficacy of many of these supplements remains
      unsubstantiated, they are widely perceived by the public to reduce the risk of
      developing prostate cancer. These data provide an insight into patient
      perceptions and misconceptions of chemopreventative strategies, and may help to
      refine recruitment efforts in multi-institutional prostate cancer prevention
      trials.

PMID- 15142143
TI  - An analysis of risk factors for biochemical progression in patients with seminal
      vesicle invasion: validation of Kattan's nomogram in a pathological subgroup.
AB  - OBJECTIVE: To assess the ability of a recently published nomogram to predict
      failure after radical retropubic prostatectomy (RRP) in a cohort of patients with
      seminal vesicle invasion (SVI) of the resected specimen, widely regarded as a
      very poor prognostic factor in patients with prostate cancer. PATIENTS AND
      METHODS: Men with SVI after RRP were analysed retrospectively; patients with
      positive lymph nodes, adjuvant radiotherapy or hormone therapy were excluded.
      Age, race, baseline prostate specific antigen (PSA) level, clinical stage,
      Gleason score, margin status, perineural invasion, capsular invasion, laterality
      and route of invasion were recorded. Biochemical recurrence was defined as one
      PSA measurement of 0.4 ng/mL. Biochemical disease-free survival probability was
      plotted using the Kaplan-Meier method. Kattan's nomogram was applied to each
      patient and a receiver-operator characteristic (ROC) curve produced to assess the
      test's reliability. RESULTS: In all, 67 patients with SVI were identified (mean
      age 64.6 years, sd 5.9; median follow-up 30.5 months). Biochemical disease-free
      survival was significantly better for men with negative margins, unilateral SVI
      and perineural invasion. No other significant factors were detected. The median
      (95% confidence limit) area under the ROC curve was 0.739 (0.604-0.847).
      CONCLUSION: There were significant prognostic differences for three of the
      factors assessed. Although components of the Kattan nomogram were not significant
      in this group its predictive value approached that found originally, suggesting
      that it can be applied to patients with SVI in helping to direct adjuvant therapy
      and guide postoperative counselling.

PMID- 15142145
TI  - Comparative evaluation of various prostate specific antigen ratios for the early
      detection of prostate cancer.
AB  - OBJECTIVE: To compare the performance of various ratios using total prostate
      specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early
      detection of prostate cancer. PATIENTS AND METHODS: The study included 535
      consecutive patients evaluated at a prostate cancer detection clinic between
      January 1998 and October 1999. Patients had blood samples drawn before
      transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA.
      Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity)
      were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA,
      tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC)
      were calculated for each ratio. The performance of each ratio over all patients
      or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated. RESULTS: Of the 535
      patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with
      tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV
      (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone.
      Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV
      (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better
      than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and
      cPSA/PV performed better than the other ratios. CONCLUSIONS: The use of PSA
      ratios gives a higher sensitivity and specificity for detecting prostate cancer
      than the use of tPSA alone.

PMID- 15142144
TI  - Preferences for sexual information resources in patients treated for early-stage
      prostate cancer with either radical prostatectomy or brachytherapy.
AB  - OBJECTIVE: To identify the preferences for sexual information resources of
      patients before and after definitive treatment for early-stage prostate cancer
      with either radical prostatectomy (RP) or brachytherapy. PATIENTS AND METHODS:
      Two hundred patients (mean age 64 years) treated with either RP or brachytherapy
      were recruited from radiation oncology (100) and urology (100) outpatient
      clinics. Patients completed a survey questionnaire to identify the types of
      information used, preferred sources of information, knowledge of treatments for
      erectile dysfunction (ED), effect of sexual function on the treatment decision,
      and the International Index of Erectile Function (IIEF) to assess their current
      level of sexual function. RESULTS: Urologists were identified as the main source
      of sexual information. Written information, Internet access and videos were
      identified as preferred sources of information before and after treatment. The
      effects of treatment on sexual function had no apparent significant influence on
      the men's definitive treatment choice. Compared with patients in the
      brachytherapy group, patients in the RP group reported having significantly
      higher levels of sexual desire (P < 0.001) after treatment, but otherwise the
      erectile domains of the groups were remarkably similar. Two-thirds of patients
      wanted more information on the effects of treatment on sexual function, and on
      available treatments for ED. CONCLUSIONS: These results support the need for
      physicians to offer patients access to information on the effect of treatment for
      early-stage prostate cancer on erectile function before and after treatment.

PMID- 15142146
TI  - Quality of life compared during pharmacological treatments and clinical
      monitoring for non-localized prostate cancer: a randomized controlled trial.
AB  - OBJECTIVES: To investigate the effects of different management strategies for non
      localized prostate cancer on men's quality of life and cognitive functioning.
      PATIENTS, SUBJECTS AND METHODS: Men with prostate cancer were randomly assigned
      to one of four treatment arms: leuprorelin, goserelin, cyproterone acetate (CPA),
      or close clinical monitoring. In a repeated-measures design, men were assessed
      before treatment (baseline) and after 6 and 12 months of treatment. A community
      comparison group of men of the same age with no prostate cancer participated for
      the same length of time. The men were recruited from public and private urology
      departments from university teaching hospitals. All those with prostate cancer
      who were eligible for hormonal therapy had no symptoms requiring immediate
      therapy. In all, 82 patients were randomized and 62 completed the 1-year study,
      and of the 20 community participants, 15 completed the study. The main outcome
      measures were obtained from questionnaires on emotional distress, existential
      satisfaction, physical function and symptoms, social and role function,
      subjective cognitive function, and sexual function, combined with standard
      neuropsychological tests of memory, attention, and executive functions. RESULTS:
      Sexual dysfunction increased for patients on androgen-suppressing therapies, and
      emotional distress increased in those assigned to CPA or close clinical
      monitoring. Compared with before treatment there was evidence of an adverse
      effect of leuprorelin, goserelin, and CPA on cognitive function. CONCLUSIONS: In
      deciding the timing of androgen suppression therapy for prostate cancer,
      consideration should be given to potential adverse effects on quality of life and
      cognitive function.

PMID- 15142147
TI  - Bacillus Calmette-Guerin therapy in stage Ta/T1 bladder cancer: prognostic
      factors for time to recurrence and progression.
AB  - OBJECTIVE: To report prognostic factors for time to recurrence and progression
      after bacillus Calmette-Guerin (BCG) prophylaxis in patients with stage Ta/T1
      papillary bladder cancer. PATIENTS AND METHODS: The clinical records were
      assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder
      cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in
      situ were excluded. The median (range) follow-up was 44 (4-155) months. The
      effect of 13 variables on the time to recurrence and progression was evaluated
      using multivariate Cox proportional hazard regression and Kaplan-Meier analyses.
      RESULTS: The recurrence rate was markedly reduced for all grades and stages.
      Patients with a negative first cystoscopy and maintenance BCG had a significantly
      longer time to recurrence than those treated with an induction course alone (P <
      0.001). Thirty-seven patients (16%) progressed in stage. The result of the first
      cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial
      instillations (P = 0.002) had prognostic importance for the time to progression.
      Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3
      10 times the expected rate. Age, number of tumours, number of positive
      cystoscopies, length of tumour history before BCG, BCG strain and treatment year
      had no influence on time to recurrence and progression. CONCLUSIONS: Maintenance
      treatment does not seem to be necessary among patients with TaG1-G2 disease after
      a negative first cystoscopy, as the progression rate was very low. One new
      finding was that BCG seemed to be equally effective among patients with or with
      no history of an upper tract tumour. Another new and surprising finding was that
      patients treated with fewer than six induction instillations, because of very
      bothersome side-effects, had an increased risk of tumour progression and of local
      failure.

PMID- 15142148
TI  - Guideline for the primary care management of male lower urinary tract symptoms.

PMID- 15142149
TI  - A randomized placebo-controlled multicentre study to evaluate the safety and
      efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA
      chronic nonbacterial prostatitis).
AB  - OBJECTIVE: To determine if finasteride can reduce symptoms in men with a clinical
      diagnosis of chronic nonbacterial prostatitis (National Institutes of Health,
      NIH, category IIIA chronic pelvic pain syndrome, CPPS) compared with placebo.
      PATIENTS AND METHODS: Men (76) with category IIIA CPPS enrolled in four North
      American prostatitis research centres were randomized after a 2-week placebo run
      in to finasteride or placebo for 6 months. The primary efficacy variable was a
      subjective overall assessment (SOA); the secondary efficacy variables included
      the NIH chronic prostatitis symptom index (NIH-CPSI) and safety data. Patients
      were assessed at screening, baseline (after the 2-week placebo run-in), 3 and 6
      months. RESULTS: Sixty-four patients had at least one assessment on medication
      (31 placebo, 33 finasteride); 75% of the finasteride and 54% of the placebo group
      had at least a mild improvement (defined as > 25% improvement in SOA), and 44%
      and 27%, respectively, a moderate or marked improvement (>50% improvement in
      SOA). The trend was similar in the NIH-CPSI scores. Five patients in the
      finasteride and seven in the placebo group reported medication-related adverse
      events. CONCLUSION: This randomized placebo-controlled pilot study suggests that
      finasteride was of benefit for some men with category IIIA CPPS, but the results
      do not justify recommending finasteride as monotherapy, except for men who also
      have benign prostatic hyperplasia. A larger, properly powered study, possibly
      evaluating combination with other therapies or specifically in men with
      prostatitis and benign prostatic hyperplasia, is required to confirm any clinical
      benefit.

PMID- 15142150
TI  - Antidiuresis: a new concept in managing female daytime urinary incontinence.
AB  - OBJECTIVE: To investigate the efficacy of desmopressin nasal spray on daytime
      urinary incontinence in women. PATIENTS AND METHODS: A multicentre,
      multinational, randomized, double-blind, placebo-controlled, cross-over
      exploratory study of women (aged 18-80 years) complaining of severe daytime
      urinary incontinence was conducted in three centres (King's College Hospital;
      Boras County Hospital and Skejby Hospital). Seventy-five patients were screened
      of whom 64 were randomized. In all, 60 women received study medication (safety
      population) and 57 completed the study. The intention-to-treat population
      comprised 59 patients and there were 41 in the per protocol analysis. The primary
      efficacy endpoint was the number of periods with no leakage for 4 h after dosing.
      Women were instructed to take the drug at a time of their choosing, but >/= 4 h
      before bedtime. Secondary efficacy variables included the time to first void or
      incontinence episode, volume leaked per incontinence episode, total volume voided
      and number of periods with no leakage. All measurements were made over 7 days on
      desmopressin and 3 days on placebo. RESULTS: There was a higher mean (sd)
      incidence of periods with no leakage in the first 4 h on desmopressin, at 62
      (35)%, than on placebo, at 48 (40)%, and during the first 8 h, at 55 (37)% vs 40
      (41)%. There was also a higher frequency of dry days on desmopressin than on
      placebo; 36% of patients had no leakage on virtually all treatment days (6 or 7)
      for 4 h after dosing. At 4-8 h the incidence of periods with no leakage on
      desmopressin was 68 (35)% vs 63 (41)% on placebo, and thereafter the incidence
      was similar. The time from dosing to first incontinence episode was longer on
      desmopressin, at 6.3 (2.5) h, vs 5.2 (3.3) h, whilst the volume leaked per
      incontinence episode was lower on desmopressin than placebo. The total volume
      voided was consistently lower on desmopressin, at 1180 (58) mL vs 1375 (57) mL,
      over the 24-h period after administration. There were no serious or severe
      adverse events reported. Seven women (11%) withdrew from the study, of whom five
      did not attend for the final visit and two (3%) because of mild adverse events.
      CONCLUSIONS: The results of this exploratory study suggest that desmopressin is
      an effective and safe treatment in women with daytime urinary incontinence, and
      allows them to choose when they need treatment, thus improving motivation, which
      may aid compliance with therapy.

PMID- 15142151
TI  - Nocturia: impact on quality of life in a Dutch adult population.
AB  - OBJECTIVE: To estimate the effect of nocturia on quality of life (QoL) and to
      assess the associated effects of sleep problems. SUBJECTS AND METHODS: From a
      random sample of Dutch adults (>/= 18 years old) 1000 were selected after
      stratification to complete a written questionnaire. Respondents (819) were
      distributed over three groups: a target group (189, who felt bothered by >/= one
      void/night); a reference group 1 (120 reporting >/= two voids/night but with no
      bother); and reference group 2 (510, with 0-1 voids/night). Nocturia, other lower
      urinary tract symptoms and perceived impact on life were measured using the
      Bristol Lower Urinary Tract Symptoms Questionnaire (B-LUTS). Sleep problems were
      measured using the Sleep Wake Experience List (SWEL) and QoL using two subscales
      from the RAND-36, i.e. 'physical functioning' and 'mental health'. RESULTS: The
      perceived impact on life was highest in the target group (P < 0.05), which also
      had more sleep problems and scored lower on the QoL scores than both reference
      groups (P < 0.05). Statistically significant differences in mental health and
      physical functioning between the target and reference groups became insignificant
      after correcting for sleep problems, indicating that the effect of nocturia (with
      bother) is mediated by sleep problems. CONCLUSIONS: Nocturia may lead to sleep
      insufficiency and consequently to a decrease in mental and physical health.
      Patients who consult a doctor for nocturia should thus be treated adequately. In
      addition, it is worthwhile for doctors to routinely check if patients who contact
      them for sleep problems also have nocturia.

PMID- 15142152
TI  - Nocturia in patients with lower urinary tract symptoms: association with diurnal
      voiding patterns.
AB  - OBJECTIVE: To determine whether diurnal voiding patterns predict nocturia in
      patients with lower urinary tract symptoms (LUTS), as few studies have evaluated
      the association between diurnal and nocturnal voiding patterns. PATIENTS AND
      METHODS: We prospectively analysed the frequency-volume charts (FVCs) of
      consecutive patients with LUTS. At the initial visit patients had a detailed
      clinical evaluation and subsequently were requested to complete a 72-h FVC. In
      all, 104 (41 men and 63 women, mean age 63 years, range 50-83) were included in
      the primary analyses. Associations between daytime variables and nocturia were
      described using maximum likelihood estimates of the relative risk and by 95%
      confidence intervals (CIs) based on logistic regression models. RESULTS: When at
      least one night-time void was used to define nocturia the multivariate logistic
      model showed a negative association of mean daytime voided volume with nocturia
      (P = 0.001). The odds ratio for nocturia decreased with this variable to 0.98
      (95% CI 0.96-0.99). When 'voiding at least twice per night' was used to define
      nocturia only the number of daytime voids was positively related to nocturia
      (odds ratio 1.22; 95% CI 1.01-1.48; P= 0.040). CONCLUSION: Nocturia may be
      associated with diurnal voiding patterns; these results also suggest that the
      causes of nocturia of one or of two or more voids may differ. This highlights the
      role of bladder function in more severe forms of nocturia.

PMID- 15142153
TI  - Use of the short form of King's Health Questionnaire to measure quality of life
      in patients with an overactive bladder.
AB  - OBJECTIVE: To develop a short version of the King's Health Questionnaire (KHQ),
      as there is a practical need to have a shorter version to summarize the eight
      domain scores into fewer domains. PATIENTS AND METHODS: Data from 293 patients
      were obtained from a randomized, double-blind, placebo-controlled clinical trial
      in Japan of oxybutynin and tolterodine in patients with symptoms of an overactive
      bladder. The KHQ has two single-item and six multiple-item domains. To construct
      the short form of the KHQ one item was selected from the each of multiple-item
      domains, based on standardized structural coefficients estimated by confirmatory
      factor analysis (CFA) in a previous study. These six items include the domains:
      'daily activities from role limitation', 'travel from physical limitation',
      'social life from social limitation', 'family life from personal relationship',
      'depressed from emotion' and 'tired from sleep and energy'. Based on the six
      selected items a series of psychometric analyses were conducted. RESULTS:
      Exploratory factor analysis (EFA) with promax rotation identified two factors
      'limitation of daily life' (LDL) and mental health. LDL consisted of 'daily
      activities', 'travel' and 'social life', and mental health included 'family
      life', 'depressed' and 'tired'. Based on the results from the EFA, the second
      order factor structure was tested by CFA. The model fitted the data well for both
      the male and female model. The KHQ short form showed excellent reliability with
      Cronbach's alpha coefficients for LDL and mental health for both genders. The
      domains in the short form were responsive to clinical efficacy variables, and had
      statistically significant sensitivity to change in the patients' perception of
      bladder condition in all domains. CONCLUSION: These analyses confirm the
      psychometric properties and clinical validity of the short-form KHQ, which
      appears to offer a practical, valid and reliable health-related quality-of-life
      instrument.

PMID- 15142154
TI  - Correlation of ultrasonographic and orchidometer measurements of testis volume in
      adults.
AB  - OBJECTIVE: To determine the correlation between testicular volume measured with
      an orchidometer or high-resolution scrotal ultrasonography (US) with colour-flow
      Doppler analysis. PATIENTS AND METHODS: In all, 159 men (mean age 36.6 years)
      presenting for infertility evaluation underwent both a physical examination by a
      one experienced examiner and high-resolution US with colour-flow Doppler
      analysis. An orchidometer was also used to measure testicular volume after
      stretching the scrotal skin tightly over the testis and after warming with a
      heating pad. The US was interpreted by a radiologist who had no knowledge of the
      orchidometer estimates. The volume was calculated as 0.71 x length x width x
      height. RESULTS: For the right testes the mean orchidometer and US estimates were
      18.4 and 18.3 mL, yielding a correlation coefficient of 0.72 (r (2) = 0.52, P <
      0.01). On the left the respective values were 17.1 and 16.9 mL, with a
      correlation coefficient of 0.69 (r (2) = 0.48, P < 0.01). CONCLUSION:
      Orchidometer estimates of testicular volume correlate closely and very
      significantly with US estimates in adults. In the hands of an experienced
      examiner orchidometer measurements provide an accurate, rapid and inexpensive
      assessment of testicular volume.

PMID- 15142155
TI  - Topical anaesthetic use for treating premature ejaculation: a double-blind,
      randomized, placebo-controlled study.
AB  - OBJECTIVE: To assess the use of a topical anaesthetic mixture to improve
      premature ejaculation (PE), for which penile hypersensitivity might be a cause.
      PATIENTS AND METHODS: The study included 42 men divided in two groups; group A
      used a lidocaine-prilocaine solution and group B used an inert cream. The tubes
      of cream were distributed randomly and participants asked to note any unpleasant
      symptoms, difficulties and the results of each attempt at intercourse, assessed
      by the intravaginal ejaculatory latency time (IELT). RESULTS: There was a
      significant increase in the mean (sd) IELT, from 1.49 (0.9) to 8.45 (0.9) min (P
      < 0.001) in group A but not in group B, at 1.67 (0.7) to 1.95 (0.12) min (P >
      0.05). CONCLUSION: We suggest that anaesthetic cream might be effective for
      treating PE.

PMID- 15142156
TI  - Cost analysis of flexible ureterorenoscopy.
AB  - OBJECTIVE: To assess the costs of flexible ureterorenoscopy. MATERIALS AND
      METHODS: Data were collected prospectively for 100 cases using a new flexible
      ureteroscope (DUR8, Circon ACMI, Stamford, USA), including the indications for
      flexible ureterorenoscopy, use of laser probes, disposable instrumentation, and
      the cost and timing of ureteroscope repair. RESULTS: Of the 100 procedures 68
      were for stone disease, 21 for known or suspected transitional cell carcinoma
      (TCC), six were diagnostic only and five were for pelvi-ureteric junction
      obstruction. The ureteroscope was repaired after the 29th and 88th cases. The
      ability of the ureteroscope to deflect was maintained throughout. At the time of
      purchase the ureteroscope was listed at pound 15 000 and each repair/exchange
      currently costs pound 4200, thus the total expenditure on the ureteroscope was
      pound 23 400. Total expenditure on ancillary equipment was pound 28 727, of which
      pound 22 927 was on disposables and pound 5800 on 10 laser probes. CONCLUSION: In
      this series the costs of the ancillary equipment exceeded the purchase and
      maintenance of the ureteroscope, and we expect this trend to continue in the long
      term. The advent of more durable ureteroscopes may ultimately reduce the
      frequency of costly repairs. The cost of disposables should be considered in
      planning the budget.

PMID- 15142157
TI  - An audit over 2 years' practice of open and laparoscopic live-donor nephrectomy
      at renal transplant centres in the UK and Ireland.
AB  - OBJECTIVE: To collate information on the practice of live-donor nephrectomy and
      compare this with the published British Transplantation Society (BTS) guidelines
      for best practice, using two questionnaires sent to all renal transplant centres
      in the UK and Ireland to cover practice for the years 2000 and 2002. METHODS: A
      postal questionnaire was sent to all surgical kidney transplant consultants in
      the UK and Ireland, including questions on the practice of live-donor nephrectomy
      in the year 2000 (the questionnaire was sent in 2001) and 2002 (questionnaire
      sent in 2003). RESULTS: All 28 centres responded fully for both years; 27 centres
      used live kidney donation in 2000, decreasing to 24 in 2002. Consultants reported
      356 operations in 2000, representing 19% of all kidney transplants, and 403 in
      2002, representing 23% of all kidney transplants. Three centres offered
      laparoscopic donor nephrectomy in 2000, and five did so in 2002. Most centres
      organize donor and recipient operations synchronously, and most have a consultant
      anaesthetist present for the donor procedure. There were variations in the use of
      analgesia and thromboprophylaxis, and in donor follow-up. CONCLUSIONS: There is
      widespread application of live-donor nephrectomy in the UK but BTS guidelines are
      not closely followed. Minimal access donor nephrectomy is offered at a few
      centres but many have plans to introduce this into their practice.

PMID- 15142158
TI  - Ureteric stenting after ureteroscopy for ureteric stones: a prospective
      randomized study assessing symptoms and complications.
AB  - OBJECTIVE: To compare patients with and with no stenting after ureteroscopy for
      ureteric calculi, as placing such stents is routine, although many patients
      complain of pain and urinary symptoms. PATIENTS AND METHODS: In all, 45 patients
      with ureteric calculi amenable to ureteroscopic management were prospectively
      randomized into a stented (23) or an unstented (22) group. Standard ureteroscopic
      basketing and lithotripsy was used, through a ureteroscope (8.5 F) with or
      without ureteric dilatation. Symptom questionnaires were completed by the
      patients after treatment, and they were followed radiographically to assess stone
      free rate and evidence of obstruction. RESULTS: There was no statistically
      significant difference in age, stone size, operative duration or hospital stay
      between the groups (P > 0.05). Furthermore, there was no statistical difference
      in flank pain or urinary symptoms (P > 0.05), except haematuria, between the
      groups; haematuria was more severe and prolonged in the stented group (P =
      0.001). CONCLUSIONS: Uncomplicated ureteroscopy for removing calculi is safe with
      no stent after treatment, and after considering complications and side-effects we
      think that the routine use of ureteric stents after uncomplicated ureteroscopy
      for stone extraction is unnecessary.

PMID- 15142160
TI  - Mainz Pouch II technique: 10 years' experience.
AB  - OBJECTIVE: To report the long-term results with the Mainz Pouch II procedure.
      PATIENTS AND METHODS: Between 1990 and 2000 a Mainz Pouch II ureterosigmoidostomy
      was used in 123 patients (49 females and 74 males, mean age 43.6 years, range: 1
      73). The indications for urinary diversion were cystectomy for bladder cancer in
      92 patients, bladder exstrophy and/or incontinent epispadias in 26, irreparable
      traumatic loss of the sphincteric urethra in four and cloacal malformation (sinus
      urogenitalis) in one. In all, 102 patients with a follow-up of >/= 12 months were
      evaluated (mean 46.2 months). RESULTS: Day- and night-time continence rates were
      97% and 95%, respectively. The remaining patients occasionally lose some drops of
      urine during coughing or straining, or reported minimal soiling of undergarments
      during the night. The mean voiding frequency was six during the day and once at
      night. There were 14 ureteric implantation stenoses (7.2% of 194 evaluated reno
      ureteric units) and they were treated successfully by open repair (13) or
      antegrade balloon dilation (one). For metabolic disturbances, 69% of the patients
      had a capillary base excess of <-2.5 mmol/L and use oral alkalinizing drugs to
      prevent hyperchloraemic acidosis. There was no clinically evident metabolic
      acidosis. CONCLUSION: Applying the principles of detubularization and spherical
      reconfiguration to create a low-pressure reservoir and stratifying ureteric
      implantation between submucosal and serous-lined extramural tunnel techniques
      succeeded in giving better continence rates and long-term preservation of the
      upper urinary tract than a classical ureterosigmoidostomy. The Mainz Pouch II
      ureterosigmoidostomy is simple and reliable as a viable alternative for continent
      urinary diversion in selected patients.

PMID- 15142161
TI  - Modified ureterosigmoidostomy (Mainz II): a long-term follow-up.
AB  - OBJECTIVE: To assess the long-term results in patients treated using a modified
      ureterosigmoidostomy (Mainz II). PATIENTS AND METHODS: Between 1994 and 1999, 17
      patients had their lower urinary tract reconstructed by a ureterosigmoidostomy,
      modified by reconfiguring the rectum to make a low-pressure reservoir (Mainz II).
      All patients were followed on a standard protocol. Data were extracted from the
      database and from a review of the case-notes. In 12 patients the procedure was
      with a radical cystectomy for carcinoma. Five had a failed conventional
      ureterosigmoidostomy for bladder exstrophy and therefore proceeded to a Mainz II.
      The data on continence and complications were retrieved for a retrospective
      analysis; the mean (range) follow-up was 6.4 (4-8.6) years. RESULTS: Ten of those
      with bladder cancer and one in the revision group were continent. Two patients in
      the revision group had sufficiently severe nocturnal incontinence to require
      conversion to a colonic conduit. Seven of the 17 patients had hyperchloraemic
      acidosis, one had pyelonephritis and one had renal stones. There were no
      anastomotic neoplasms. CONCLUSION: The Mainz II has a good outcome if used as the
      primary procedure. In patients with an existing ureterosigmoidostomy who are
      incontinent, detubularization of the rectosigmoid alone is unlikely to restore
      continence.

PMID- 15142162
TI  - Experience with non-cycled artificial urinary sphincters.
AB  - OBJECTIVE: To report our experience in children and adolescents with a non-cycled
      artificial urinary sphincter. While some children with the AUS can void, others
      require clean intermittent catheterization (CIC) through the sphincter or an
      alternative site for catheterization; in some of the latter we have either not
      cycled (pumped) an activated AUS or the AUS has failed, and there is concern
      about ischaemia in some adults with a non-cycled AUS. PATIENTS AND METHODS: In
      all, 143 patients who had an AUS placed between 1980 and 2002 were reviewed
      retrospectively; 15 (10 boys and five girls) no longer cycled (pumped) their AUS.
      The mean age at AUS insertion was 11 years and the mean (range) follow-up after
      insertion was 10.4 (1.64-22.2) years. The diagnoses included myelomeningocele in
      11, sacral agenesis in three and cloaca in one. Nine patients have an activated
      functioning AUS and in six the AUS does not function; in the first nine the
      sphincter has not routinely been cycled (pumped) for a mean (range) of 1.6 (0.6
      2.9) years. In the other six with a nonfunctioning AUS the mean (range)
      observation period is 6.4 (1.5-10) years since the system has not functioned.
      RESULTS: All patients were completely continent, including the six with a
      nonfunctioning AUS. After inserting the AUS, two patients voided in combination
      with CIC (one each urethral and abdominal stoma) and 13 emptied by CIC (nine
      abdominal stoma, four urethral). There was a mechanical complication in eight
      patients; three had the AUS repaired and are dry, and five are dry with no
      repair. In one patient the AUS was never activated. To date there has been no
      erosion of the cuff in any of the 15 patients with a non-cycled AUS. CONCLUSION:
      The AUS remains an extremely reliable procedure to achieve continence in children
      and young adults. It is versatile and can be combined with other procedures that
      provide an alternative means for catheterization. While some have noted the need
      to routinely cycle the AUS to prevent erosion, this has not been our experience
      in these 15 patients.

PMID- 15142163
TI  - Late renal functional and morphological evaluation after non-operative treatment
      of high-grade renal injuries in children.
AB  - OBJECTIVE: To assess the long-term results in children with high-grade renal
      trauma who were managed without surgery, as such treatment was initially
      successful but little is known about the late ipsilateral renal function and
      morphology. PATIENTS AND METHODS: The study included 13 children (nine boys and
      four girls; mean age 8 years, sd 5) with high-grade renal injury who were managed
      without surgery between 1997 and 2001, and followed for a mean (sd, range) of 3
      (2, 0.5-7) years. The trauma was caused by a motor-car accident in five and
      falling from a height in eight children, and was on the right in 10 and on the
      left in three. There was gross and microscopic haematuria in 10 and three
      patients, respectively. The trauma was graded according to the American
      Association for Surgery of Trauma, with grades III, IV and V renal injury in six,
      four and three children, respectively. All patients were treated initially by
      observation; one required super-selective embolization because of continuing
      haemorrhage. Three children with progressive urinary extravasation were treated
      with a percutaneous tube drain and JJ stent for 6 weeks. Patients were discharged
      after a mean (sd) hospital stay of 9 (6) days. Ultrasonography then showed
      resolving haematoma in all patients with a mean (sd) size of 7 (2) cm(2). At the
      last follow-up patients were re-evaluated by a clinical examination, renal
      scintigraphy and computed tomography angiography. RESULTS: None of the children
      was hypertensive nor had any abnormality on urine analysis; all had normal serum
      creatinine levels, and scintigraphy and angiography showed normal contralateral
      kidneys in all. Ipsilateral abnormalities were detected in 12 patients, and
      included a single scar in five, multiple scars in six and a cystic lesion with
      multiple septa in one. There was no vascular complication or hydronephrosis, and
      no significant functional loss, with all affected kidneys having a split function
      of 41-50% at the last follow-up. CONCLUSION: Although there is no late functional
      loss there are residual morphological changes in almost all children with high
      grade renal injury. This study provides objective support for the non-operative
      management of high-grade renal injury in children, but a prolonged follow-up is
      warranted to assess the risk of progression of these abnormalities.

PMID- 15142164
TI  - Comprehensive analysis of tubularized incised-plate urethroplasty in primary and
      re-operative hypospadias.
AB  - OBJECTIVE: To retrospectively review our experience of the tubularized incised
      plate (TIP) urethroplasty over the last 4 years. PATIENTS AND METHODS: From 1998
      to December 2001, 133 patients (mean age 7 years, sd 4, range 1-22), had a TIP
      urethroplasty by one surgeon for primary (103) and re-operative (30) hypospadias;
      the defects included 106 (79%) distal and mid-shaft, and 27 (21%) posterior
      shaft. The neourethra was covered by a subcutaneous flap in 66 (50%) patients or
      by corpus spongiosa (spongioplasty) in 31 (23%), with no cover in the remaining
      36 (27%). In the last 20 patients (15%) a modified meatoplasty was used; the site
      and size of the new meatus was predetermined on the glans around a suitable
      catheter before any incision. Urethral stents were not used after repair in 39
      (29%) patients, and regular meatal dilation was used only in patients with
      voiding difficulty and obvious tendency to stenosis. The presence of
      complications requiring re-operation and overall general appearance were
      recorded. RESULTS: The mean (sd) follow-up was 10 (5) months; there were 24
      complications in 20 patients (15%), including a small fistula in 12 (9%),
      complete disruption of the repair in 4 (3%), meatal stenosis in seven (5%) and
      neourethral stricture in one (0.8%). Complications were not significantly
      different between primary and re-operative cases, and unaffected by the use of
      the stents. On univariate analysis complications were significantly higher with
      running than interrupted sutures, in repairs in the first 2 years of the study,
      in patients with posterior hypospadias, and in those with no neourethral
      coverage. However, the last two factors were the only significant independent
      risk factors in a multivariate analysis. Regular urethral dilatation was
      indicated in 43 patients (32%). Modified meatoplasty was associated with a
      significantly lower requirement for regular dilatation (P < 0.05) and no meatal
      stenosis. In the 113 complication-free patients the operation gave an excellent
      cosmetic appearance with a vertical slit meatus on the tip of conical glans in
      110 (97%); there was slight meatal retraction in the remaining three patients.
      CONCLUSION: The TIP repair is a reliable method for treating both distal and
      proximal penile shaft hypospadias, is suitable for both primary and re-operative
      cases, and is more versatile than other repairs. Covering the neourethra with a
      flap or spongioplasty significantly improves the results. Regular urethral
      dilatation is required in a third of patients but modified meatoplasty obviates
      the need for regular dilatation and eliminates the risk of meatal stenosis.

PMID- 15142165
TI  - The exstrophy-epispadias complex: is aesthetic appearance important?
AB  - OBJECTIVE: To show the relevance of cosmetic appearance in the adequate treatment
      of patients with exstrophy-epispadias complex (EEC), and to indicate that surgery
      by experienced teams can improve the long-term treatment forecast and the
      patient's body image. PATIENTS AND METHODS: From 1978 to 2002, 71 patients
      diagnosed with EEC were treated in the authors' institution; 24 (aged 2-23 years)
      were selected to undergo different surgical procedures. The criterion for surgery
      considered interviews conducted by the psychology team with the parents and
      children. The plastic surgery and paediatric urology teams carried out the
      procedures jointly; the follow-up was 0.33-7 years. RESULTS: Five female patients
      and six male had abdominoplasty to treat multiple scars; eight had intermittent
      catheterization conduits repositioned from the right iliac fossa to the
      umbilicus. Six female patients had plastic surgery of the external genitalia and
      three had a broad mobilization of the urogenital sinus. Thirteen male patients
      had a small penis and had the corpora cavernosa fully mobilized and the penis
      reconstructed. Five female patients and one male had anterior osteotomy. One
      patient with no left testis had it replaced and one patient with uterine prolapse
      had the uterus fixed to the posterior abdominal wall. Six patients had a second
      procedure, in two because the outcome of the initial operation was poor and in
      the others to complement the initial treatment. In all but one patient there was
      an improvement in the objective criteria, e.g. school absences, difficulty in
      establishing long-lasting social relationships and refusal to participate in
      sports activities. However, none of the patients would attempt sexual
      intercourse. CONCLUSIONS: Body image, self-esteem, sexuality, sexual function and
      fertility are deemed crucial by adolescents; in patients with EEC customised
      surgical procedures can give a satisfactory aesthetic outcome, and be a further
      reason for adequately following occasional urinary complications and renal
      function, to avoid loss to follow-up.

PMID- 15142166
TI  - Urothelium regeneration using viable cultured urothelial cell sheets grafted on
      demucosalized gastric flaps.
AB  - OBJECTIVE: To evaluate urothelium regeneration by grafting viable cultured
      urothelial cell sheets, harvested from temperature-responsive culture surfaces,
      on demucosalized gastric flaps in a dog model. MATERIALS AND METHODS: Viable
      urothelium was obtained from eight beagle dogs by partial cystectomy. Harvested
      urothelial cells were seeded on temperature-responsive culture dishes modified
      with the thermally sensitive polymer, poly(N-isopropylacrylamide). Urothelial
      cells cultured for 3 weeks generated contiguous urothelial cell sheets that were
      noninvasively harvested with no enzymatic treatment from these dishes, by
      reducing culture temperature. Urothelial cell sheets were autografted onto
      surgically demucosalized gastric flaps. Three weeks after autografting the dogs
      were killed and the gastric flaps with the urothelial cell sheets were examined.
      Cell and tissue characteristics were compared between these urothelial cell sheet
      grafted gastric flaps and native urothelium. Ultrafine structures were also
      examined by electron microscopy. RESULTS: Five of the eight urothelial cell sheet
      grafted flaps showed viable urothelial regeneration. Urothelial cell sheets
      attached spontaneously to demucosalized tissue surfaces completely, with no
      suture or fixing, and developed into a stratified viable epithelium very similar
      to native urothelium. Regenerated urothelium remained unstained by antiproton
      pump antibody, which typically stains epithelial cells positively in gastric
      mucosal layers. On three of the eight flaps where there were severe haematomas,
      grafted cell sheets were not adherent and there was no urothelial regeneration.
      CONCLUSIONS: Urothelial cell sheets were autografted onto dog demucosalized
      gastric flaps successfully, with no suture or fixation, generating a multilayered
      urothelium in vivo. The novel intact cell-sheet grafting method rapidly produces
      native-like epithelium in vivo. This versatile technology should prove useful in
      urinary tract tissue engineering and surgical reconstruction.

PMID- 15142167
TI  - Protein kinase C-alpha in prostate cancer.

PMID- 15142168
TI  - Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in
      the NBT-II bladder tumour cell line.
AB  - OBJECTIVES: To examine the growth inhibition and cell cycle arrest effects of
      epigallocatechin gallate (EGCG), a major constituent of green tea polyphenols, on
      the NBT-II bladder tumour cell line. MATERIALS AND METHODS: Growth inhibition and
      cell cycle arrest effects of EGCG were evaluated by the tetrazolium assay, flow
      cytometry and apoptotic DNA ladder tests. The cell cycle-related oncogene and
      protein expressions in NBT-II bladder tumour cells, when incubated with EGCG,
      were detected with reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blot analysis. RESULTS: EGCG inhibited growth of the NBT-II bladder
      tumour cells in a dose- and time-dependent manner. Flow cytometry showed a G0/G1
      arrest in cells when cultured with EGCG at doses of 10, 20 or 40 micro mol/L for
      48 or 72 h. The apoptotic DNA ladder test showed that EGCG at 10 micro mol/L
      induced early apoptosis after 48 h of incubation. A down-regulation of cyclin D1
      was detected by RT-PCR when the cells were incubated with EGCG (20 micro mol/L
      for 48 h. EGCG also down-regulated protein expression of cyclin D1, cyclin
      dependent kinase 4/6 and phosphorylated retinoblastoma protein, in both a time-
      and dose-dependent manner, when detected by Western blot. CONCLUSION: EGCG had
      growth inhibition and cell-cycle arrest effects in NBT-II bladder tumour cells by
      down-regulating the cyclin D1, cyclin-dependent kinase 4/6 and retinoblastoma
      protein machinery for regulating cell-cycle progression.

PMID- 15142169
TI  - Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth
      factor, and microvessel invasion, in renal cell carcinoma.
AB  - OBJECTIVE: To determine if use of cell proliferation, cell adhesion, level of
      angiogenesis-related factors and presence of microscopic vascular invasion (MVI)
      could better predict the biological behaviour of renal cell carcinoma (RCC),
      which has a widely variable clinical outcome despite the use of conventional
      prognostic factors (staging and grading). MATERIALS AND METHODS: The expression
      of Ki-67, CD44H and vascular endothelial growth factor (VEGF) were assessed
      immunohistochemically in formalin-fixed, paraffin-embedded tissues from 48 RCCs,
      using a Ki-67 labelling index (LI), CD44 LI and level of VEGF expression,
      respectively. In addition all the pathological slides were reviewed
      retrospectively for the presence and absence of MVI. The prognostic value of all
      the variables assessed was then evaluated, and correlated with the usual
      prognostic variables and cancer-specific survival. RESULTS: Univariate analysis
      of cancer-specific survival showed that tumour stage (P < 0.001), tumour size (P
      = 0.005), metastasis, MVI, Ki-67 LI, CD44H LI and VEGF expression (all P < 0.001)
      were predictors of tumour-related death. There was a statistical correlation
      between CD44H LI and each of Ki-67 LI (r = 0.61), expression level of VEGF (r =
      0.72) and presence of MVI (r = 0.71). Independent predictors of cancer-specific
      survival in a multivariate analysis were: in all patients with RCC, the MVI (P =
      0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P =
      0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki-67
      LI (P = 0.003). No independent predictor was identified in patient with
      metastases. CONCLUSION: This study suggests that cell proliferation, cell
      adhesion, the level of VEGF expression and the presence of MVI represent a
      complex tumour-host interaction that may favour the progression of RCC. Cell
      proliferation, CD44H and VEGF expression appear to be powerful markers for
      identifying patients with an adverse prognosis.

PMID- 15142170
TI  - Effect of insulin-like growth factor-1 on apoptosis of rat testicular germ cells
      induced by testicular torsion.
AB  - OBJECTIVE: To investigate the possible protective role of insulin-like growth
      factor-1 (IGF-1, reported to have a protective effect in experimental models of
      hypoxic ischaemia), and the involvement of apoptotic cell death in a model of
      torsion/detorsion of the rat testis. MATERIALS AND METHODS: Adult male Wistar
      rats were divided into five groups of five rats each. Group 1 underwent a sham
      operation as a control; in group 2 the testis was twisted and in group 3 then
      untwisted; in group 4 IGF-1 was injected subcutaneously just before bilateral
      torsion, and then the right testis removed after 4 h and the left after 24 h; in
      group 5, IGF-1 was injected immediately after bilateral detorsion and then the
      testes removed as in group 4. Both testicles were examined histologically, with
      apoptosis detected using the in situ DNA fragmentation (TUNEL) system, with
      combined enzymology and immunohistochemistry techniques. RESULTS: In groups 2
      (torsion) and 3 (detorsion), light microscopy of the testis showed some
      degenerative changes in the germ cells. Compared to group 1, apoptosis was more
      significant in group 3 than in the other groups. Group 4 (torsion/IGF-1) had a
      similar number of apoptotic germ cells as in group 2 (torsion) after 24 h, but
      fewer than the same group after 4 h. In group 5 (detorsion/IGF-1), apoptosis was
      reduced by IGF-1 significantly more than in group 3 (P < 0.05). Apoptosis was
      significantly less in spermatids in group 5 than in group 3 (P < 0.05).
      CONCLUSIONS: IGF-1 seems to lower the levels of germ cell apoptosis, which may be
      important for protecting the testes from torsion/detorsion injury. Further
      clinical studies are needed to evaluate this protective effect in testicular
      torsion/detorsion.

PMID- 15142172
TI  - Stress incontinence: help at hand.

PMID- 15142171
TI  - In vivo transfer of a neuronal nitric oxide synthase expression vector into the
      rat bladder by electroporation.
AB  - OBJECTIVE: To investigate the possibility of in vivo gene transfer by attempting
      to transfer the neuronal nitric oxide synthase (nNOS) gene into rat bladder using
      electroporation. MATERIALS AND METHODS: The bladder was exposed through an
      abdominal midline incision in 8-week-old male rats. Plasmid DNA of the marker
      genes green fluorescent protein (GFP) and luciferase, and the nNOS gene, was then
      injected into the subserosal space of the bladder and electroporation applied. At
      72 h after gene transfer, GFP and luciferase were assayed in the isolated bladder
      and immunohistochemical staining used to detect nNOS; NO(x) released from
      isolated bladder strips was also assessed using microdialysis and high
      performance liquid chromatography. RESULTS: From the luciferase assay, 45 V, 1
      Hz, 50 ms and eight pulses were selected as the optimum conditions for
      electroporation. Bladder specimens with GFP genes injected by electroporation
      showed bright and numerous sites of GFP expression in the smooth muscle layer. In
      rats with the nNOS gene injected by electroporation there was marked nNOS
      immunoreactivity, and NO(x) released from bladder strips was significantly
      greater than in the control groups. CONCLUSIONS: These results suggest that
      electroporation is a useful technique for in vivo gene transfer into rat bladder
      smooth muscles, and that the nNOS gene transferred by this procedure functionally
      expresses and contributes to NO production.

PMID- 15142173
TI  - Onlay urethroplasty after sectioning of the urethral plate: early clinical
      experience with a new approach - the 'three-in-one' technique.

PMID- 15142174
TI  - Transrectal ultrasonography-guided echo-enhanced seminal vesiculography in
      combination with transurethral resection of the ejaculatory ducts.

PMID- 15142177
TI  - A randomized crossover study to evaluate Ro 115-1240, a selective alpha
      adrenoceptor partial agonist in women with stress urinary incontinence.

PMID- 15142179
TI  - Urinary markers for urothelial cancer.

PMID- 15142178
TI  - The management of hormone-relapsed prostate cancer.

PMID- 15142180
TI  - The role of neuromodulation in the management of urinary urge incontinence.

PMID- 15142181
TI  - Repeating the measurement of prostate-specific antigen in symptomatic men can
      avoid unnecessary prostatic biopsy.

PMID- 15142182
TI  - Bladder wall tension during physiological voiding and in patients with an
      unstable detrusor or bladder outlet obstruction.

PMID- 15142183
TI  - Use of the 'labelled key-ring clock': a simple technique for urethral-bladder
      neck anastomosis.

PMID- 15142184
TI  - Brachytherapy: the surgeon's perspective.

PMID- 15142185
TI  - Transurethral resection vs microwave thermotherapy of the prostate: a cost
      consequences analysis.

PMID- 15142186
TI  - The use of flutamide as a single antiandrogen treatment for hormone-refractory
      prostate cancer.

PMID- 15142187
TI  - The clinical implications of the Prostate Cancer Prevention Trial (PCPT).

PMID- 15142188
TI  - Pyeloplasty (Anderson-Hynes).

PMID- 15142193
TI  - Review article: new pharmacological agents for the treatment of gastro
      oesophageal reflux disease.
AB  - Proton pump inhibitors, which act at the terminal point of acid secretion--the
      H+, K+-ATPase--are currently the most effective pharmacological treatments
      available for reflux disease. Despite the efficacy of the proton pump inhibitors,
      there is still potential for clinical improvement in gastro-oesophageal reflux
      disease pharmacotherapy. Faster onset of complete acid inhibition and improved
      duration of efficacy are two potential areas for improvement A number of novel
      pharmaceutical agents are currently undergoing clinical evaluation for the
      treatment of gastro-oesophageal reflux disease. These include transient lower
      oesophageal sphincter relaxation-reducing agents, serotonergic
      agents/prokinetics, potassium-competitive acid blockers, mucosal protectants,
      histamine H3 agonists and anti-gastrin agents. One or more of these drug groups
      may represent the future medical therapy for gastro-oesophageal reflux disease,
      should they prove effective in the clinical setting. This review summarizes the
      state of the art with these agents.

PMID- 15142195
TI  - Laboratory markers predict bone loss in Crohn's disease: relationship to blood
      mononuclear cell function and nutritional status.
AB  - BACKGROUND: Crohn's disease is associated with reduced bone density. The power of
      simple markers of systemic inflammation to identify higher rates of bone loss, in
      Crohn's disease, is uncertain. This relationship and the role of circulating
      (peripheral blood) mononuclear cells were investigated in a case-control study.
      METHODS: Urinary deoxypyridinoline/creatinine and serum osteocalcin
      concentrations were compared in male and premenopausal females with "active"
      Crohn's disease (C-reactive protein > or = 10 and/or erythrocyte sedimentation
      rate > or = 20) (n = 22) and controls with "quiescent" Crohn's disease (C
      reactive protein < 10 and erythrocyte sedimentation rate < 20) (n = 21). No
      patients were receiving corticosteroid therapy. Production of tumour necrosis
      factor-alpha, interferon-gamma and prostaglandin E(2) by peripheral blood
      mononuclear cells were measured. RESULTS: Active Crohn's disease was associated
      with a higher deoxypyridinoline/creatinine (P = 0.02) and
      deoxypyridinoline/creatinine:osteocalcin ratio (P =0.01) compared with quiescent
      Crohn's disease, but similar osteocalcin (P = 0.24). These were not explained by
      vitamin D status, dietary intake or nutritional status. However, production of
      interferon-gamma by concanavalin A-stimulated peripheral blood mononuclear cells
      was lower in active Crohn's disease (P = 0.02) and correlated negatively with the
      deoxypyridinoline/creatinine:osteocalcin ratio (r = -0.40, P = 0.004).
      CONCLUSION: In Crohn's disease, raised C-reactive protein and erythrocyte
      sedimentation rate may indicate higher rates of bone loss and, if persistent, the
      need to assess bone mass even where disease symptoms are mild. This may be partly
      explained by altered production of interferon-gamma by peripheral blood
      mononuclear cells.

PMID- 15142194
TI  - Review article: prevention of non-steroidal anti-inflammatory drug
      gastrointestinal complications--review and recommendations based on risk
      assessment.
AB  - The incidence of non-steroidal anti-inflammatory drug-related ulcer complications
      remains high despite the availability of potent anti-ulcer drugs and selective
      cyclo-oxygenase-2 inhibitors. Non-steroidal anti-inflammatory drug-related ulcer
      complications can be minimized by prospective assessment of patients' baseline
      risk, rational choice and use of non-steroidal anti-inflammatory drugs, and
      selective use of co-therapy strategies with gastroprotectives. Current
      recommendations regarding strategies using anti-ulcer drugs and cyclo-oxygenase-2
      inhibitors for prevention of clinical non-steroidal anti-inflammatory drug upper
      gastrointestinal events are largely derived from studies using surrogates such as
      endoscopic ulcers, erosions, and symptoms in low- to average-risk patients.
      Conclusions based on surrogate and potentially manipulatable end-points are
      increasingly suspect with regard to applicability to clinical situations. This
      article reviews the risks associated with non-steroidal anti-inflammatory drugs
      including aspirin and includes the effect of the patients' baseline risk, and the
      confounding effects of Helicobacter pylori infection. In addition, uncertainties
      regarding the clinical efficacy of anti-ulcer drugs and cyclo-oxygenase-2
      inhibitors against non-steroidal anti-inflammatory drug-related ulcer
      complications are put into perspective. We propose management strategies based on
      the risk category: low risk (absence of risk factors) (least ulcerogenic non
      steroidal anti-inflammatory drug at lowest effective dose), moderate risk (one to
      two risk factors) (as above, plus an antisecretory agent or misoprostol or a
      cyclo-oxygenase-2 inhibitor), high risk (multiple risk factors or patients using
      concomitant low-dose aspirin, steroids, or anticoagulants) (cyclo-oxygenase-2
      inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton
      pump inhibitors or misoprostol with aspirin), and very high risk (history of
      ulcer complications) (avoid all non-steroidal anti-inflammatory drugs, if
      possible or a cyclo-oxygenase-2 plus a proton pump inhibitors and/or
      misoprostol). The presence of H. pylori infection increases the risk of upper
      gastrointestinal complications in non-steroidal anti-inflammatory drug users by
      two- to fourfold suggesting that all patients requiring regular non-steroidal
      anti-inflammatory drug therapy be tested for H. pylori.

PMID- 15142196
TI  - Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with
      ileocecal resection and are a risk factor for reoperation.
AB  - BACKGROUND: Mutations within the NOD2/CARD15 gene have recently been shown to be
      associated with Crohn's disease. AIMS: To investigate the clinical impact of the
      three common NOD2/CARD15 mutations in patients with Crohn's disease. METHODS: We
      investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp,
      Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with
      ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence
      of NOD2/CARD15 mutations were correlated to clinical and demographical
      parameters. RESULTS: In Crohn's disease patients, 35.6% carried at least one
      mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with
      ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype
      phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at
      disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal
      resections (P = 0.0002). Interestingly, reoperation with resection of the
      anastomosis was significantly more frequent in patients with NOD2/CARD15
      mutations (P = 0.01). CONCLUSIONS: Our investigations support the current
      hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's
      disease with younger age at diagnosis, ileal involvement, ileocecal resections
      and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations
      might therefore be used to identify high risk patients for relapse prevention
      strategies.

PMID- 15142197
TI  - Predicting the outcome of severe ulcerative colitis: development of a novel risk
      score to aid early selection of patients for second-line medical therapy or
      surgery.
AB  - BACKGROUND: The failure rate of medical therapy in severe ulcerative colitis is
      high. A risk index, to aid the identification of patients of not responding at an
      early stage to intravenous corticosteroid therapy, would be useful to facilitate
      second-line treatment or surgery. METHODS: We recruited 167 consecutive patients
      with severe ulcerative colitis between January 1995 and March 2002; and employed
      multiple logistic regression to analyse parameters within the first 3 days of
      medical therapy. We applied statistical modelling to formulate a risk score
      according to the likelihood of medical failure. RESULTS: Sixty-seven (40%)
      patients failed to respond to medical therapy. Multiple logistic regression
      analysis identified mean stool frequency and colonic dilatation within the first
      3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001,
      0.001 and 0.002 respectively). A numerical risk score was formulated based on
      these variables. Patients with scores of 0-1, 2-3 and > or =4 had a medical
      therapy failure rate of 11%, 43% and 85% respectively. Receiver-operator
      characteristic analysis of this score yielded area under curve of 0.88, with a
      sensitivity of 85% and specificity of 75% using score > or =4 in predicting non
      response. CONCLUSION: This risk score allows the early identification of patients
      with severe ulcerative colitis who would be suitable for second-line medical
      therapy or surgery.

PMID- 15142199
TI  - Health-related quality of life in patients with cardiovascular disease--the
      effect of upper gastrointestinal symptom treatment.
AB  - BACKGROUND: Upper gastrointestinal discomfort decreases the already impaired
      health status of patients with cardiovascular disease. AIM: To evaluate whether
      acid suppressive therapy improves health-related quality of life in patients who
      developed upper gastrointestinal symptoms after starting low-dose acetylsalicylic
      acid. METHODS: In a double-blind, placebo-controlled randomized trail, cardiac
      patients using low-dose (80 mg) acetylsalicylic acid with (n = 142) and without
      (n = 90) upper gastrointestinal symptoms were included. Patients with symptoms
      were treated with rabeprazole or placebo for 4 weeks. At baseline and 4 weeks
      information about gastrointestinal symptoms and health-related quality of life
      was assessed. RESULTS: The 73 patients assigned to rabeprazole when compared with
      69 patients given placebo reported the same quality of life scores 4 weeks after
      randomization. The differences in quality of life scores between patients with
      and without symptoms at baseline remained after 4 weeks. Patients in whom
      treatment led to complete symptom relief or those who remained symptom-free
      reported significantly higher scores for Physical Component Summary (P < 0.01)
      and Mental Component Summary (P < 0.01), when compared to those with persistent
      symptoms or new onset symptoms. CONCLUSION: Proton-pump inhibitor therapy did not
      improve quality of life. Upper gastrointestinal symptom relief in itself
      considerably increased quality of life.

PMID- 15142198
TI  - Comparative pharmacokinetics of equimolar doses of 5-aminosalicylate administered
      as oral mesalamine (Asacol) and balsalazide: a randomized, single-dose, crossover
      study in healthy volunteers.
AB  - BACKGROUND: Existing pharmacokinetic data are insufficient to determine whether a
      delayed-release formulation of mesalamine (Asacol) results in greater systemic
      exposure to 5-aminosalicylic acid and its major metabolite N-acetyl-5
      aminosalicylic acid than a prodrug (balsalazide). AIM: To determine the
      pharmacokinetic parameters of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic
      acid from equimolar doses of 5-aminosalicylic acid administered as Asacol and
      balsalazide. METHODS: Nineteen healthy volunteers completed an open-label, single
      dose, randomized, crossover study comparing the pharmacokinetics of 5
      aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5
      aminosalicylic acid (800 mg) administered as Asacol (800 mg) and balsalazide
      (2250 mg). Plasma and urine samples were analysed for 5-aminosalicylic acid, N
      acetyl-5-aminosalicylic acid, and balsalazide (urine only) using high-performance
      liquid chromatography methods with mass spectrometric detection. Pharmacokinetic
      parameters assessed for 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid
      included: percentage of dose excreted in urine (A(e)%), area under the plasma
      concentration-time curve (AUCt(last)); and maximum plasma concentration (C(max)).
      RESULTS: The geometric mean total (5-aminosalicylic acid and N-acetyl-5
      aminosalicylic acid) urinary excretion values (A(e)%) of Asacol and balsalazide
      were 19.26 and 19.31% (P = 0.98). The geometric mean A(e)% values of 5
      aminosalicylic acid for Asacol and balsalazide were 0.39 and 0.37% (P = 0.78);
      the geometric mean A(e)% values of N-acetyl-5-aminosalicylic acid for Asacol and
      balsalazide were 18.78 and 18.83% (P = 0.98). The geometric mean 5-aminosalicylic
      acid AUC(t(last)) values for Asacol and balsalazide were 3295 and 3449 ng h/mL (P
      = 0.85); the geometric mean N-acetyl-5-aminosalicylic acid AUC(t(last)) values
      for Asacol and balsalazide were 15 364 and 16 050 ng h/mL (P = 0.69). The
      geometric mean 5-5-aminosalicylic acid C(max) values for Asacol and balsalazide
      were 319 and 348 ng/mL (P = 0.80); the geometric mean N-acetyl-5-aminosalicylic
      acid C(max) values for Asacol and balsalazide 927 and 1009 ng/mL (P = 0.67).
      CONCLUSIONS: The systemic absorption of 5-aminosalicylic acid and N-acetyl-5
      aminosalicylic acid from Asacol and balsalazide are comparable based upon plasma
      pharmacokinetic parameters and urinary excretion values.

PMID- 15142200
TI  - Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal
      acid breakthrough.
AB  - BACKGROUND: Twice-daily dosing is increasingly used to improve gastric acid
      control, although not all proton-pump inhibitors are more effective when doses
      are split. Standard dose esomeprazole provides better gastric acid control than
      other standard dose proton-pump inhibitors. AIMS: To compare the effect of
      standard dose esomeprazole (1 x 40 mg) with 20 mg b.d. on gastric acidity.
      METHODS: Thirteen healthy subjects participated in this crossover study,
      receiving esomeprazole 2 x 20 mg and 1 x 40 mg for 7 days in random order with a
      washout period of at least 7 days. Gastric 24-h pH was measured on days 1, 2 and
      6. RESULTS: Median gastric 24-h pH was higher during 2 x 20 mg esomeprazole on
      day 2 (P < 0.01), no differences were detected on day 6. Night-time gastric acid
      suppression was significantly improved by 2 x 20 mg esomeprazole on all study
      days (P < 0.05). Nocturnal acid breakthrough was observed on all study days in
      subjects receiving 1 x 40 mg, but in only 85% (first night), 64% (second night),
      and 45% of subjects (sixth night) with 2 x 20 mg (P < 0.05). CONCLUSION:
      Splitting the esomeprazole dose improves initial acid suppression, this effect
      starts at the first night. Maximal benefit is achieved on day 2, while the effect
      on night-time acid control is detectable during the entire first week of
      treatment.

PMID- 15142201
TI  - Evaluation of the pharmacokinetics and pharmacodynamics of intravenous
      lansoprazole.
AB  - AIM: To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg
      administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally.
      METHODS: Twenty-nine subjects received lansoprazole orally on days 1-7 and
      intravenous lansoprazole in NaCl on days 8-14. Blood samples were collected on
      days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated
      maximal acid output were determined on days -1, 8, 9 and 15. Thirty-six different
      subjects received one of four regimen sequences: intravenous lansoprazole in
      NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo,
      each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5.
      RESULTS: Intravenous and per oral lansoprazole for 7 days produced equivalent
      basal acid output and maximal acid output suppression. Pharmacokinetics and mean
      pH values with intravenous lansoprazole in NaCl or polyethylene glycol were
      equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6
      that were significantly greater than did per orally. CONCLUSIONS: Intravenous
      lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene
      glycol, and its onset of action is faster than per oral lansoprazole.

PMID- 15142202
TI  - The effect of an empirical trial of high-dose lansoprazole on symptom response of
      patients with non-cardiac chest pain--a randomized, double-blind, placebo
      controlled, crossover trial.
AB  - BACKGROUND: Empirical trial with high-dose omeprazole has been shown to be a
      sensitive tool for diagnosing patients with gastro-oesophageal reflux disease
      related non-cardiac chest pain. AIM: To determine the clinical value of an
      empirical trial of high-dose lansoprazole in detecting patients with gastro
      oesophageal reflux disease-related non-cardiac chest pain. METHODS: Patients who
      were referred by a cardiologist after a comprehensive evaluation, with at least
      three episodes per week of unexplained chest pain as the predominant symptom,
      were enrolled into the study. Oesophageal mucosal disease was determined by upper
      endoscopy followed by 24-h oesophageal pH monitoring to assess acid exposure.
      Patients were then randomized to either placebo or lansoprazole 60 mg am and 30
      mg pm for 7 days. After a washout period of 1 week, patients crossed over to the
      other arm of the study for an additional 7 days. Patients completed a daily diary
      assessing severity and frequency of chest pain as the predominant symptom
      throughout the baseline treatment and washout periods. The lansoprazole empirical
      trial was considered diagnostic if chest pain score improved > or =50% than
      baseline. RESULTS: Of the 40 patients with non-cardiac chest pain that were
      enrolled, 18 (45%) had erosive oesophagitis and/or abnormal pH test (gastro
      oesophageal reflux disease-positive) and 22 (55%) had both tests negative (gastro
      oesophageal reflux disease-negative). Of the gastro-oesophageal reflux disease
      positive patients, 14 (78%) had significantly higher symptom improvement on
      lansoprazole than on placebo (22%) (P = 0.0143). Of the gastro-oesophageal reflux
      disease-negative group, two (9.1%) markedly improved on the medication and eight
      (36.3%) on placebo (P = 0.75). The sensitivity and specificity of the
      lansoprazole empirical trial was 78 and 80%, respectively. By day 2, 12 (85.7%)
      of the gastro-oesophageal reflux disease-related non-cardiac chest pain
      responders had either complete or almost complete symptom resolution.
      CONCLUSIONS: The lansoprazole empirical trial is highly sensitive and specific
      for diagnosing gastro-oesophageal reflux disease-related non-cardiac chest pain
      patients. The trial enables diagnosing most of the responders within the first 2
      days and thus a shorter duration of therapy may be considered in a subset of non
      cardiac chest pain patients.

PMID- 15142203
TI  - Management of defecation disorders with botulinum neurotoxin.

PMID- 15142204
TI  - Polyethylene glycol for constipation.

PMID- 15142206
TI  - Green tea.

PMID- 15142208
TI  - Mast cells--a role in periodontal diseases?
AB  - OBJECTIVES: Limited attention has been given to the role mast cells may play in
      periodontal diseases. BACKGROUND: Mast cells are indeed found abundantly below
      and within several types of mucosal epithelia. On the basis of their proteinase
      content, mast cells are divided into connective tissue (CT) and mucosal
      phenotypes. The CT phenotype contains both tryptase and chymase (MC(TC)), while
      the mucosal phenotype contains only tryptase (MC(T)). The in vivo significance of
      different mast cell phenotypes has not yet been fully established. Mast cells are
      able to phagocytose, process and present antigens as effectively as macrophages.
      RESULTS: Recently mast cells were found in high numbers in chronically inflamed
      gingival tissue taken from patients with chronic marginal periodontitis (CMP).
      The number of mast cells was found to be even higher in HIV(+) patients with CMP.
      Furthermore, mast cells also express strongly matrix metalloproteinases (MMPs),
      which are key enzymes in degradation of gingival extracellular matrix. Mast cells
      may release preformed cytokines directing local innate and adaptive immune
      responses. The present review will focus on possible roles for mast cells in
      periodontal diseases. CONCLUSIONS: We certainly feel that this is a key cell in
      inflamed periodontal tissue and its role in periodontitis needs to be revisited.

PMID- 15142210
TI  - Non-surgical periodontal treatment with a new ultrasonic device (Vector
      ultrasonic system) or hand instruments.
AB  - OBJECTIVES: The aim of this prospective, randomized, controlled clinical study
      was to compare the effectiveness of a newly developed ultrasonic device to that
      of scaling and root planing for non-surgical periodontal treatment. MATERIAL AND
      METHODS: Thirty-eight patients with moderate to advanced chronic periodontal
      disease were treated according to an "one-stage procedure" with either a newly
      developed ultrasonic device (VUS) (Vector-ultrasonic system) or scaling and root
      planing (SRP) using hand instruments. Clinical assessments by plaque index (PlI),
      gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival
      recession (GR), and clinical attachment level (CAL) were made prior to and at 6
      months after treatment. Differences in clinical parameters were analyzed using
      the Wilcoxon signed ranks test and Mann and Whitney U-test. RESULTS: No
      differences in any of the investigated parameters were observed at baseline
      between the two groups. The mean value of BOP decreased in the VUS group from 32%
      at baseline to 20% after 6 months (p<0.001) and in the SRP group from 30% at
      baseline to 18% after 6 months (p<0.001). The results have shown that at
      moderately deep sites (initial PD 4-5 mm) mean CAL changed in the test group from
      4.6+/-1.2 to 4.2+/-1.6 mm (p< 0.001) and in the control group from 4.8+/-1.3 to
      4.4+/-1.5 mm (p<0.001). At deep sites (initial PD>6 mm) mean CAL changed in the
      test group from 8.5+/-1.9 to 7.9+/-2.4 mm (p<0.001) and in the control group from
      7.9+/-1.6 to 7.2+/-2.2 mm (p<0.001). No statistically significant differences in
      any of the investigated parameters were found between the two groups. CONCLUSION:
      Non-surgical periodontal therapy with the tested ultrasonic device may lead to
      clinical improvements comparable to those obtained with conventional hand
      instruments.

PMID- 15142209
TI  - Antibiotic resistance profile of the subgingival microbiota following systemic or
      local tetracycline therapy.
AB  - BACKGROUND: Tetracyclines have been extensively used as adjunctives to
      conventional periodontal therapy. Emergence of resistant strains, however, has
      been reported. This study evaluated longitudinally the tetracycline resistance
      patterns of the subgingival microbiota of periodontitis subjects treated with
      systemic or local tetracycline therapy+scaling and root planing (SRP). METHODS:
      Thirty chronic periodontitis patients were randomly assigned to three groups:
      SRP+500 mg of systemic tetracycline twice/day for 14 days; SRP alone and
      SRP+tetracycline fibers (Actsite) at four selected sites for 10 days. Subgingival
      plaque samples were obtained from four sites with probing pocket depths (PPD)> or
      =6 mm in each patient at baseline, 1 week, 3, 6 and 12 months post-therapy.
      Samples were dispersed and diluted in pre-reduced anaerobically sterilized
      Ringer's solution, plated on Trypticase Soy Agar (TSA)+5% blood with or without 4
      microg/ml of tetracycline and incubated anaerobically for 10 days. The percentage
      of resistant microorganisms were determined and the isolates identified by DNA
      probes and the checkerboard method. Significance of differences among and within
      groups over time was sought using the Kruskal-Wallis and Friedman tests,
      respectively. RESULTS: The percentage of resistant microorganisms increased
      significantly at 1 week in the tetracycline groups, but dropped to baseline
      levels over time. The SRP+Actsite group presented the lowest proportions of
      resistant species at 6 and 12 months. No significant changes were observed in the
      SRP group. The predominant tetracycline-resistant species included Streptococcus
      spp., Veillonela parvula, Peptostreptococcus micros, Prevotella intermedia,
      Gemella morbillorum and Actinobacillus actinomycetemcomitans (Aa). A high
      percentage of sites with resistant Aa, Porphyromonas gingivalis and Tanerella
      forsythensis was observed in all groups at baseline. However, T. forsythensis was
      not detected in any group and P. gingivalis was not present in the SRP+Actsite
      group at 1 year post-therapy. Aa was still frequently detected in all groups
      after therapy. However, the greatest reduction was observed in the SRP+Actsite
      group. CONCLUSION: Local or systemically administered tetracycline results in
      transitory selection of subgingival species intrinsically resistant to this drug.
      Although the percentage of sites harboring periodontal pathogens resistant to
      tetracycline were quite elevated in this population, both therapies were
      effective in reducing their prevalence over time.

PMID- 15142211
TI  - An in situ model to study the toothpaste abrasion of enamel.
AB  - OBJECTIVES: In order to understand the clinical relevance of dentifrice
      abrasivity on the dentition in vivo, an in situ enamel wear model has been
      developed. MATERIALS AND METHODS: Polished human enamel blocks were indented with
      a Knoop diamond, attached to dentures and worn by adult volunteers for 24 h per
      day. The blocks were brushed for 30 s, twice per day with dentifrices of known
      relative dentine abrasivity (RDA) and relative enamel abrasivity (REA). The
      dentifrices used were either dentifrice A (RDA=85, REA=3.4), dentifrice B
      (RDA=189, REA=2.0) or dentifrice C (RDA=132, REA=42.7). After 28 days, the blocks
      were removed and the geometry of each Knoop indent was remeasured. From the
      baseline and post-treatment values of indent length, the amount of enamel wear
      was calculated from the change in the indent depth. RESULTS: The median values
      for enamel wear of dentifrices A, B and C were -0.02, 0.01 and -0.48 microm,
      respectively. The differences between dentifrice C and dentifrices A and B were
      of statistical significance. CONCLUSION: This study has demonstrated the
      usefulness of an in situ technique for investigating the relationship between the
      abrasivity of a dentifrice in vitro and the wear of enamel in situ.

PMID- 15142212
TI  - Periodontal repair in dogs: examiner reproducibility in the supraalveolar
      periodontal defect model.
AB  - BACKGROUND: Histometric assessments are routinely used to evaluate biologic
      events ascertained in histologic sections acquired from animal and human studies.
      The objective of this study was to evaluate the intra- and inter-examiner
      reproducibility of histometric assessments in the supraalveolar periodontal
      defect model. METHODS: Histometric analysis using incandescent and polarized
      light microscopy, an attached digital camera system, and a PC-based image
      analysis system including a custom program for the supraalveolar periodontal
      defect model was performed on histologic sections acquired from one jaw quadrant
      in each of 12 dogs. The animals had received an experimental protocol including
      implantation of a coral biomaterial and guided tissue regeneration (GTR) barrier
      devices, and were evaluated following a 4-week healing interval. Histometric
      parameters were recorded and repeated within a 3-month interval by two examiners
      following brief training. Intra- and inter-examiner reproducibility was assessed
      using the intra-class correlation coefficient (ICC). RESULTS: Most parameters
      showed high intra-examiner ICCs. Parameters including defect height, connective
      tissue repair, bone regeneration (height/area), formation of a junctional
      epithelium, positioning of the GTR device, ankylosis, root resorption, and defect
      area yielded an ICC> or 0..9. The ICCs for bone density and biomaterial density
      were somewhat lower (0.8 and 0.7, respectively). The inter-examiner
      reproducibility was somewhat lower compared to the intra-examiner
      reproducibility. Nevertheless, the ICCs were generally high (ICC range: 0.6-0.9).
      CONCLUSIONS: Histometric evaluations in the supraalveolar periodontal defect
      model yield highly reproducible results, in particular when a single examiner
      performs the histometric measurements, even when the examiner was exposed to
      limited training.

PMID- 15142213
TI  - Interleukin 10 gene promoter polymorphisms are associated with chronic
      periodontitis.
AB  - BACKGROUND: Chronic periodontitis (CP) is characterized by an inflammation in the
      supporting tissues of the teeth caused primarily by bacterial infection.
      Interleukin 10 (IL10) is an anti-inflammatory cytokine whose genetic
      polymorphisms may influence the expression of the protein. OBJECTIVE: In this
      study we investigated the hypothesis that single-nucleotide polymorphisms (SNPs)
      in the promoter of IL10 gene might be related to CP. MATERIALS AND METHODS: DNA
      was obtained from n=67 CP patients and n=43 control subjects. All studied
      individuals were non-smokers. The -1087 SNP was investigated by DNA sequencing,
      and the -819 and -592 SNPs by restriction fragment length polymorphism of PCR
      products. RESULTS: Frequencies of -819 and -592 SNPs showed differences between
      the control and CP groups. The ACC haplotype was more prevalent in the control
      group and the ATA haplotype more prevalent in the CP group. The ATA haplotype
      seemed to increase susceptibility to CP in women (odds ratio (OR)=2.57). The
      heterozygous haplotype GCC/ACC was predominant in the control group (OR=8.26;
      p=0.001). CONCLUSIONS: Specific haplotypes and SNPs in IL10 gene are associated
      with susceptibility to CP in Brazilian patients.

PMID- 15142214
TI  - Lack of association between the TNF alpha G -308 A promoter polymorphism and
      periodontal disease.
AB  - BACKGROUND: Immunorelevant gene polymorphisms might influence the susceptibility
      for periodontal disease. The present study assessed the frequency of a promoter
      polymorphism (-308G-to-A) of the tumour necrosis factor (TNF)alpha gene in
      patients with periodontitis and controls. METHODS: Eighty-one patients with
      generalized chronic periodontitis and 80 healthy controls were genotyped for the 
      308 polymorphism of the TNF alpha gene by PCR amplification and subsequent
      restriction fragment length polymorphism analysis. The diagnosis of chronic
      periodontitis was made for each subject on basis of standardized clinical and
      radiographic criteria. RESULTS: In patients with peridontitis and controls, the
      frequency of the TNF alpha-308 A allele was comparable (19.1% [31/162] versus
      13.8% [22/160]; p=0.193). CONCLUSION: The present study revealed no association
      between the -308 TNF alpha gene polymorphism and periodontal disease.

PMID- 15142215
TI  - Impact of oral health on the life quality of periodontal patients.
AB  - OBJECTIVES: To assess the impact of oral health on the life quality of a
      periodontal patient group. MATERIALS AND METHODS: Two hundred and five patients
      attending a private periodontal clinic completed a questionnaire incorporating
      the 16-item UK oral health-related quality-of-life measure (OHQoL-UK), a check
      list of questions about their periodontal health over the past year and a
      comprehensive periodontal examination. RESULTS: The effect of oral health on
      quality of life was considerable, with many individuals experiencing negative
      impacts across a broad range of physical, social and psychological aspects of
      life quality. OHQoL-UK(Copyright ) scores was associated with patient's self
      reported periodontal health in the past year: experiences of "swollen gums"
      (p<0.01), "sore gums" (p<0.01), "receding gums" (p<0.01), "loose teeth" (p<0.01),
      "drifting teeth" (p<0.01), "bad breath" (p<0.01) and "toothache" (p<0.01). In
      addition, OHQoL-UK scores were correlated with the number of teeth with pocket
      depths of 5 mm or more (r(s)-0.42, p<0.01). New patients had poorer oral health
      related quality of life compared with the treated maintenance group (p<0.01).
      CONCLUSIONS: Periodontal status impacts on life quality. This has implications in
      understanding the consequences of periodontal health and in the use of patient
      centred outcomes in periodontal research.

PMID- 15142216
TI  - Atmospheric contamination during ultrasonic scaling.
AB  - OBJECTIVE: The aim of this study was to determine the microbial atmospheric
      contamination during initial periodontal treatment using a piezoelectric
      ultrasonic scaler in combination with either high-volume evacuation (HVE) or
      conventional dental suction (CDS). METHODS: The study included 17 treatment
      sessions, consisting of a 40-min episode of continuous plaque and calculus
      removal using an ultrasonic unit (EMS). The treatment sessions were carried out
      in six patients with generalized adult periodontitis and ranged from two to four
      sessions per patient according to their needs. The use of HVE and CDS was
      randomly assigned over the sessions within each patient. Before each treatment,
      the operating room was not used for 15 h. To measure baseline microbial air
      pollution two Petri dishes containing blood agar were exposed for 10 min to the
      air. At the start of each treatment session, two Petri dishes were exposed for 5
      min at a distance of 40 cm from the mouth of the patients. After 20 min, this
      procedure was repeated. At a distance of 150 cm, two Petri dishes were exposed
      for 20 min followed by exposure of two new Petri dishes for the rest of the
      session. The plates were cultured aerobically and anaerobically for 3 and 7 days,
      respectively. RESULTS: The mean colony forming units (CFU) before treatment never
      exceeded 0.6 colonies per plate. At 40 cm, the mean CFU, when considering a
      period of 40 min, was 8.0 for HVE and 17.0 for CDS. The mean CFU at 150 cm during
      this period was 8.1 with HVE and 10.3 with the CDS. With reference to the Air
      Microbial Index the operatory atmosphere was considered to be in a good condition
      during 40 min of continuous use of the ultrasonic scaler in combination with both
      HVE and CDS. CONCLUSION: Within the restrictions of this study, only limited
      atmospheric microbial contamination is produced when using a piezoelectric
      ultrasonic scaler.

PMID- 15142217
TI  - Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with
      severe chronic periodontitis.
AB  - BACKGROUND: Genetic polymorphisms for cytokines and their receptors have been
      proposed as potential markers for periodontal disease. Tumor necrosis factor
      receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent
      studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and
      other diseases. OBJECTIVES: The aim of the present study is to evaluate whether
      TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP).
      METHODS: One hundred and ninety-six unrelated subjects (age 40-65 years) with
      different levels of CP were identified according to established criteria,
      including measurements of probing pocket depth (PPD), clinical attachment level
      (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non
      smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene
      was detected by a polymerase chain reaction-restriction fragment length
      polymorphisms (PCR-RFLP) method. RESULTS: The frequency and the positivity of the
      +587G allele were significantly higher in severe CP patients than in controls
      (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values
      of PPD, CAL, and BL were significantly higher in the +587G allele positive than
      in the negative subjects (p=0.035, 0.022, and 0.018, respectively). CONCLUSIONS:
      These findings suggest that the TNFR2(+587G) polymorphic allele could be
      associated with severe CP in Japanese.

PMID- 15142218
TI  - Effect of two toothcleaning frequencies on periodontal status in patients with
      advanced periodontitis.
AB  - OBJECTIVE: To compare the effect of once a day toothcleaning with once in 2 days
      toothcleaning in patients with advanced periodontitis. MATERIAL AND METHODS:
      Twenty-two patients, aged 34-54 years were given intensive oral hygiene (OH) and
      half their mouth root planed with re-assessment 6 weeks later. The patients were
      randomised into either a once a day toothcleaning group or a once in 2 days
      toothcleaning group. The effects of the two cleaning regimens were assessed
      during a 6-week follow-up period. Two patients were excluded from the study.
      Analysis of covariance was used to test the difference between the two groups at
      baseline and at 6 weeks. RESULTS: There was a statistically significant
      difference between the two groups in plaque reduction (p=0.01) and reduction of
      probing pocket depth >6 mm (p=0.05) in the OH-only sites. No significant
      difference was found between the two cleaning regimens in the combined oral
      hygiene with root planing sites. CONCLUSION: The present study demonstrated that
      in patients with advanced periodontitis, once a day toothcleaning is more
      effective than once in 2 days toothcleaning in otherwise untreated sites.

PMID- 15142221
TI  - Education in the broader sense.
AB  - Education is the key element in medical science. It is generally divided into pre
      graduate, postgraduate and continuing medical education, with the physician as
      the main target. It usually covers aetiology, diagnosis, treatment, prognosis,
      outcome and long-term effects. Neurology is a large field in medical science,
      focusing on diseases of the brain, the spinal cord, the peripheral nerves and
      muscles. They tend to be chronic and, often progressive, leading to long-term
      disability and handicap for the individual, frequently associated with personal,
      social and emotional consequences. In the time span of a patient with a
      neurological disease, interaction with physicians is important and often vital,
      but interaction with other health groups and relatives or other caregivers is
      longer and more intensive. The knowledge and experience of the patient and
      caregiver is equally important, in that an informed patient or caregiver is more
      likely to participate actively and be of greater benefit in disease management.
      This paper promotes the concept that education in neurology should be integrated
      to include the physicians and other professionals as well as patients, caregivers
      and public. A broader awareness of neurological diseases will draw support and
      improve the approach of society to the provision of resources and management of
      these illnesses, as well as public attitude towards the symptoms and to those who
      live with them. Two bodies have collaborated in writing this article: the
      education committee of the EFNS and the EFNA.

PMID- 15142219
TI  - Bone resorbing activity and cytokine levels in gingival crevicular fluid before
      and after treatment of periodontal disease.
AB  - BACKGROUND: The aim of the present study was to investigate bone resorption
      activity (BRA), interleukin-1 alpha (IL-1 alpha), IL-1 beta and interleukin-1
      receptor antagonist (IL-1ra) in gingival crevicular fluid (GCF) in sites with no
      signs of periodontal disease and in sites with horizontal or angular loss of
      periodontal bone. These assessments were performed before and after periodontal
      treatment. METHODS: GCFs were collected from 10 individuals with filter strips
      from two healthy sites and four sites with deep pathological periodontal pockets,
      two of which showed horizontal bone loss and two with angular bone loss. All
      diseased pockets were treated with flap surgery and systemic Doxyferm. Twelve
      months later GCF was collected again and treatment outcome evaluated. BRA in GCFs
      was assessed in a bone organ culture system by following the release of (45)Ca
      from neonatal mouse calvariae. The amounts of IL-1 alpha, IL-1 beta and IL-1ra in
      GCFs were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Treatment resulted in reduction of pocket depths with 3.5+/-0.5 mm in sites with
      angular bone loss and 2.8+/-0.3 mm in sites with horizontal bone loss. Initially,
      BRA, IL-1 alpha, IL-1 beta and IL-1ra were significantly higher in GCFs from
      diseased sites compared with healthy sites. No differences in BRA and cytokine
      levels were seen between GCFs from pockets with horizontal and angular bone
      losses. The levels of IL-1 alpha, IL-1 beta and IL-1ra were significantly reduced
      after treatment of diseased pockets. Pocket depths were significantly correlated
      to BRA only in pre-treatment sites with angular bone loss. BRA was correlated to
      Il-1 alpha, IL-1 beta, but not to IL-1ra, in diseased sites with angular bone
      loss, before and after treatment. The reductions of BRA in the individual sites,
      seen after treatment, were not correlated to the reductions of Il-1 alpha, IL-1
      beta or IL-1ra. CONCLUSIONS: These data show that BRA and cytokine levels are
      increased in GCFs from sites with periodontal disease and that periodontal
      treatment results in reduction of the cytokines. Our findings further indicate
      that IL-1 alpha and IL-1 beta play important roles for the BRA present in GCFs,
      but that other factors also contribute to this activity.

PMID- 15142222
TI  - Guidelines for the diagnosis and management of neurological complications of HIV
      infection.
AB  - The spectrum of neurological complications of HIV-infection has remained
      unchanged through the years, but its epidemiology changed remarkably as a result
      of the introduction of highly active antiretroviral therapy (HAART). Guidelines
      for the diagnosis and treatment of cerebral toxoplasmosis, cryptococcal
      meningitis, progressive multifocal leukoencephalopathy, CMV encephalitis, CMV
      polyradiculomyelitis, tuberculous meningitis, primary CNS lymphoma, HIV dementia,
      HIV myelopathy and HIV polyneuropathy are given with a grading of evidence and
      recommendations.

PMID- 15142223
TI  - High-resolution sonography of the peripheral nervous system -- a review of the
      literature.
AB  - High-resolution sonography is capable of depicting peripheral nerves and the
      brachial plexus. In this study we review the literature on this subject. Normal
      peripheral nerves have a characteristic echotexture. Most nerves are readily
      visualized, although this is not always the case with the nerves of the lower
      extremity. The main pathological changes that can be demonstrated are nerve
      enlargement and increased hypoechogenicity. In order to demonstrate nerve
      enlargement, measurements should be performed and compared with a set of
      reference values. Several neuropathies have been studied by means of
      ultrasonography. However, many studies concern case reports and show
      methodological shortcomings. The best studied peripheral neuropathy is the carpal
      tunnel syndrome in which ultrasonography seems to have an additional value when
      combined with nerve conduction studies. Nerve enlargement has also been
      demonstrated in radial neuropathy at the humerus and in ulnar neuropathy at the
      elbow. The role of sonography in various hereditary and inflammatory neuropathies
      is uncertain although diffuse nerve thickening could be demonstrated. Further
      systematic studies are needed to determine the role of sonography in the
      diagnostic process of the various neuropathies. It would be important to study
      the subcategories of patients in whom electrodiagnostic studies are normal or
      show equivocal findings.

PMID- 15142224
TI  - Psychiatric comorbidity in a population of Parkinson's disease patients.
AB  - Behavioural disturbances are frequently observed in Parkinson's disease (PD),
      including mood and anxiety disorders. The existence of a comorbidity between such
      psychiatric disorders in PD patients has been suggested only in a few studies. To
      assess the prevalence of mood and anxiety disturbances, and the rate of
      comorbidity of such disorders in PD. Secondary aim was to correlate the
      prevalence of psychiatric disorders in PD with age, sex, laterality of motor
      symptomatology, clinical features, severity of disease, age of onset and PD
      duration, and anti-parkinsonian therapy. Ninety consecutive PD outpatients, and
      90 age- and sex-matched controls were included. All PD patients enrolled were non
      fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD
      patients and controls with Mini Mental State Examination score <23 were excluded.
      Psychiatric diagnosis was performed by semistructured interview according with
      DSM-IV criteria and the severity of depressive and anxious symptoms was rated
      with clinical rating scales. Major depression was found in 21.1% PD patients vs.
      3.3% controls (P < 0.01, chi-square analysis), dystimia in 18.8% PD patients vs.
      4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P
      < 0.01). No difference in the prevalence of other anxiety disorders was observed
      between the two groups. The comorbidity of mood and anxiety disorders was found
      in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported
      between the prevalence of behavioural disturbances and any of the demographic,
      clinical or pharmacological data taken into account. Our findings might suggest
      the existence of a wide spectrum of psychiatric disorders in PD ranging from pure
      depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety
      disorders, presumably linked to the same neurobiological substrate.

PMID- 15142225
TI  - Chlamydia pneumoniae infection in young stroke patients: a case--control study.
AB  - Retrospective and cross-sectional studies have suggested that both bacterial and
      viral infections may be risk factors for atherosclerosis, ischemic stroke and
      acute coronary events. The correlation between Chlamydia pneumoniae and
      atherosclerosis remains a source of controversy. Our case-control study is aimed
      at evaluating the frequency of C. pneumoniae infection in a cohort of young
      adults with recent cerebrovascular disease and in particular etiologic stroke
      subtypes. Chlamydia pneumoniae IgG, IgM and IgA antibodies were evaluated by
      microimmunofluorescence method and antibody titers to both recombinant antigens
      chlamydial outer protein 2 and 60-kDa chlamydial heat shock protein (HSP60) by
      ELISA. The two groups differed with regard to the prevalence of C. pneumoniae IgA
      (P < 0.001) and IgG (P < 0.0001), as well as the titer of anti-R-HSP60 IgG (P <
      0.001). We found an increase in IgA titers, suggestive of persistent, chronic
      active infection, in 16 patients in whom the etiology of the cerebral ischemic
      event was large-vessel atherothrombosis. Persistent, active C. pneumoniae
      infection may be an additional risk factor for ischemic stroke mainly of
      atherotrombotic origin in young subjects. However, a large-scale prospective
      confirmation of our findings is required.

PMID- 15142226
TI  - Significance of serum soluble thrombomodulin level in acute cerebral infarction.
AB  - The purpose of the present study was to investigate sequential changes in serum
      soluble thrombomodulin (sTM) concentrations in patients with acute cerebral
      infarction (ACI), and to correlate sTM concentrations with the severity of ACI
      evaluated by Japan Stroke Scale. Eighty-three consecutive patients with ACI were
      enrolled, and blood examinations were carried out soon after admission and 1
      month after. sTM concentrations at admission in patients with cardioembolic
      infarction (3.2 +/- 1.2 ng/ml) were significantly lower than those of lacunar
      infarction (3.9 +/- 1.2) (P < 0.05). Serial examinations revealed that sTM
      concentrations increased significantly 1 month after admission (3.8 +/- 1.2),
      compared with those at admission (3.6 +/- 1.2) (P = 0.02). Of three ACI subtypes,
      sTM concentrations during 1 month significantly increased in atherothrombotic
      infarction (P = 0.002) or, not significantly, in cardioembolic infarction (P =
      0.09). The sTM concentrations at admission showed a significant inverse
      correlation with the severity of ACI (P = 0.04). Although sTM concentrations
      serve as a useful marker for endothelial cell damage, they are decreased in
      patients with severe ACI, especially in atherothrombotic and cardioembolic
      infarctions. Lower sTM concentrations may play some important role in disease
      progression or in the recurrence following ACI, although the exact mechanism of
      this unique result should be clarified.

PMID- 15142227
TI  - Patients with multiple sclerosis prefer early diagnosis.
AB  - The new diagnostic criteria for multiple sclerosis (MS) allow for a definite
      diagnosis in earlier stages of the disease. Yet, clinicians may hesitate to
      pursue a diagnosis of multiple sclerosis at the presentation of first symptoms
      because they consider an early diagnosis of limited benefit to patients. It is
      unknown whether patients themselves prefer to be informed in an early phase. We
      studied satisfaction with the timing of diagnosis in patients recently diagnosed
      with MS and found that 75% was satisfied, 24% favoured an earlier, and only 6% a
      later disclosure of the diagnosis. Patients who preferred an earlier diagnosis
      had a significantly longer interval between their first visit to the neurologist
      and the disclosure of diagnosis (P < 0.001). The probability that the patient was
      satisfied with the timing of diagnosis did not substantially decrease in the
      months following the first visit to the neurologist, leaving ample opportunity
      for a thorough evaluation of the early clinical course. We conclude that patients
      with MS prefer an early diagnosis.

PMID- 15142228
TI  - Unusual neurological presentations of vitamin B(12) deficiency.
AB  - Vitamin B(12) deficiency (B(12)D) has a wide variety of neurological symptoms and
      signs. However, cerebellar dysfunction and cranial neuropathies other than optic
      neuropathy have been rarely reported. Herein, we describe two cases of unusual
      neurological manifestations of B(12)D. One patient showed prominent hoarseness
      with vocal cord paralysis, myelopathy, and peripheral neuropathy. The other had
      gait disturbance, lateral gaze limitation and cerebellar dysfunction in addition
      to the typical manifestations of subacute combined degeneration. Vitamin B(12)
      deficiency can rarely affect cerebellum and cranial nerves other than optic
      nerve.

PMID- 15142229
TI  - Creutzfeldt-Jakob disease presenting as progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disorder
      characterized by an akinetic rigid syndrome with vertical supranuclear
      ophthalmoplegia, early falls, and levodopa resistance. The pathological substrate
      of PSP consists of filamentous tau degenerative lesions affecting neurons and
      glia. Other disorders can present with a similar clinical picture, most commonly
      corticobasal degeneration and multiple system atrophy. Non-neurodegenerative
      disorders are rare causes of the PSP syndrome. In this report we describe
      clinical and pathological features of two cases of Creutzfeldt-Jakob disease
      (CJD) presenting with the PSP syndrome and discuss which features may help
      prevent misdiagnosis. To our knowledge, this is the first report of cases of CJD
      with autopsy confirmation that presented with a PSP syndrome.

PMID- 15142231
TI  - Fulminant cryptococcal meningitis as presenting feature in a patient with AIDS.

PMID- 15142230
TI  - A registry-based, case-control investigation of Parkinson's disease with and
      without cognitive impairment.
AB  - In approximately 40% of the patients, Parkinson's disease (PD) is complicated by
      cognitive impairment. The objective of this study was to evaluate the impact of
      cognitive impairment on disease severity and motor function in idiopathic PD
      patients. Forty-one PD patients with cognitive impairment (PD-CI) (Mini-Mental
      State Examination < or =24) and 41 PD patients without cognitive impairment (PD
      Control) matched for age at onset and duration of the disease were examined using
      the Unified Parkinson's Disease Rating Scale (UPDRS). PD patients with cognitive
      impairment had overall poorer motor function, worse rigidity (both axial and
      limb) and bradykinesia, as well as worse performance in activities of daily
      living compared with matched PD patients without cognitive impairment. This could
      either be attributed to a direct effect of cognitive impairment on parkinsonian
      symptoms or to decreased compliance of patients during clinical examination. PD
      patients should be routinely and carefully screened for dementia and caregivers
      should be aware of the effect of dementia on PD.

PMID- 15142232
TI  - Acute disseminated encephalomyelitis: clinical features and HLA-DR linkage.

PMID- 15142241
TI  - Metagenomics: from acid mine to shining sea.

PMID- 15142242
TI  - Biofilm formation by the small colony variant phenotype of Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an ubiquitous environmental bacterium and an
      opportunistic human pathogen. Not only in most natural habitats but also within
      the human host, e.g. within the chronically infected cystic fibrosis lung, P.
      aeruginosa is associated with surfaces in structures known as biofilms. These
      functional communities represent a unique mode of bacterial growth where bacteria
      display particular phenotypes that are fundamentally different from planktonic
      cells. In this review the issue of the molecular mechanisms underlying the
      emergence of small colony variant (SCV) P. aeruginosa morphotypes that are
      especially capable of forming biofilms is addressed. It is assumed that the
      expression of the chaperone usher pathway (cup) genes encoding putative fimbrial
      adhesins is responsible for the phenotypic switch to an autoaggregative SCV
      phenotype. The elucidation of phenotypic switching in response to environmental
      stimuli will significantly increase our understanding of regulatory processes
      during bacterial adaptation and might be the basis for the initiation of the
      development of new antimicrobial treatment strategies.

PMID- 15142244
TI  - Proposal to transfer 'Aegyptianella ranarum', an intracellular bacterium of frog
      red blood cells, to the family Flavobacteriaceae as 'Candidatus Hemobacterium
      ranarum' comb. nov.
AB  - 'Aegyptianella ranarum' (order Rickettsiales), an ultrastructurally defined
      small, Gram-negative rod, is known to replicate in the red blood cells of frogs.
      Heretofore, this bacterium has not been characterized genetically. We cloned and
      sequenced the 16S rRNA (1310 bp) and gyrB (718 bp) genes of 'A. ranarum' from a
      Canadian frog blood specimen. In situ hybridization (with an 'A. ranarum' 16S
      rRNA gene polymerase chain reaction product as probe) and electron microscopy
      confirmed that 'A. ranarum' forms cytoplasmic inclusions in frog erythrocytes.
      blast comparisons with GenBank 16S rRNA and gyrB sequences showed that both 'A.
      ranarum' genes were most similar (91% and 67% identity) to those of
      Chryseobacterium meningosepticum, a bacterium in the family Flavobacteriaceae. In
      contrast, 'A. ranarum' 16S rRNA shared only 61% identity with Aegyptianella
      pullorum. Phylogenetic analyses of these genes using phylip supported 'A.
      ranarum' as a member of Flavobacteriaceae, but suggested that its cladistic
      sibling may be Bergeyella zoohelcum or Weeksella virosa, rather than C.
      meningosepticum. We propose to classify 'Aegyptianella ranarum' as 'Candidatus
      Hemobacterium ranarum' in the family Flavobacteriaceae. Our results provide a
      starting point for studies of related intraerythrocytic bacterial infections in
      frogs.

PMID- 15142243
TI  - Bacterial signal transduction network in a genomic perspective.
AB  - Bacterial signalling network includes an array of numerous interacting components
      that monitor environmental and intracellular parameters and effect cellular
      response to changes in these parameters. The complexity of bacterial signalling
      systems makes comparative genome analysis a particularly valuable tool for their
      studies. Comparative studies revealed certain general trends in the organization
      of diverse signalling systems. These include (i) modular structure of signalling
      proteins; (ii) common organization of signalling components with the flow of
      information from N-terminal sensory domains to the C-terminal transmitter or
      signal output domains (N-to-C flow); (iii) use of common conserved sensory
      domains by different membrane receptors; (iv) ability of some organisms to
      respond to one environmental signal by activating several regulatory circuits;
      (v) abundance of intracellular signalling proteins, typically consisting of a PAS
      or GAF sensor domains and various output domains; (vi) importance of secondary
      messengers, cAMP and cyclic diguanylate; and (vii) crosstalk between components
      of different signalling pathways. Experimental characterization of the novel
      domains and domain combinations would be needed for achieving a better
      understanding of the mechanisms of signalling response and the intracellular
      hierarchy of different signalling pathways.

PMID- 15142245
TI  - Repression of Pseudomonas putida phenanthrene-degrading activity by plant root
      extracts and exudates.
AB  - The phenanthrene-degrading activity (PDA) of Pseudomonas putida ATCC 17484 was
      repressed after incubation with plant root extracts of oat (Avena sativa), osage
      orange (Maclura pomifera), hybrid willow (Salix alba x matsudana), kou (Cordia
      subcordata) and milo (Thespesia populnea) and plant root exudates of oat (Avena
      sativa) and hybrid poplar (Populus deltoides x nigra DN34). Total organic carbon
      content of root extracts ranged from 103 to 395 mg l(-1). Characterization of
      root extracts identified acetate (not detectable to 8.0 mg l(-1)), amino acids
      (1.7-17.3 mg l(-1)) and glucose (1.6-14.0 mg l(-1)), indicating a complex mixture
      of substrates. Repression was also observed after exposure to potential root
      derived substrates, including organic acids, glucose (carbohydrate) and glutamate
      (amino acid). Carbon source regulation (e.g. catabolite repression) was
      apparently responsible for the observed repression of P. putida PDA by root
      extracts. However, we showed that P. putida grows on root extracts and exudates
      as sole carbon and energy sources. Enhanced growth on root products may
      compensate for partial repression, because larger microbial populations are
      conducive to faster degradation rates. This would explain the commonly reported
      increase in phenanthrene removal in the rhizosphere.

PMID- 15142246
TI  - Pathogenic potential of environmental Klebsiella pneumoniae isolates.
AB  - Klebsiella pneumoniae is an important opportunistic pathogen and a frequent cause
      of nosocomial infections. K. pneumoniae infections can occur at nearly any body
      site; however, urinary tract infections and infections of the respiratory tract
      predominate. Infections are frequently preceded by gastrointestinal colonization,
      and the gastrointestinal tract is believed to be the most important reservoir for
      transmission of the bacteria. In contrast to many other bacterial pathogens, K.
      pneumoniae is ubiquitous in nature. Several studies have described Klebsiella
      isolates of environmental origin to be nearly identical to clinical isolates with
      respect to several phenotypic properties. However, the pathogenic potential of
      environmental K. pneumoniae isolates is essentially unknown. We have evaluated
      the virulence of K. pneumoniae strains of environmental and clinical origin
      directly in animal models, i.e. in urinary tract infection and intestinal
      colonization models. Furthermore, the ability to adhere to and invade human
      epithelial cell lines was examined. Although strain-to-strain differences were
      observed in the individual infection models, overall, strains of environmental
      origin were found to be as virulent as strains of clinical origin. The ubiquity
      of K. pneumoniae in nature and the general ability of K. pneumoniae strains to
      infect susceptible hosts might explain the high frequency of opportunistic
      infections caused by this species.

PMID- 15142247
TI  - Isolation of haloarchaea that grow at low salinities.
AB  - Summary Archaea, the third domain of life, were long thought to be limited to
      environmental extremes. However, the discovery of archaeal 16S rRNA gene
      sequences in water, sediment and soil samples has called into question the notion
      of Archaea as obligate extremophiles. Until now, none of these novel Archaea has
      been brought into culture, a critical step for discovering their ecological
      roles. We have cultivated three novel halophilic Archaea (haloarchaea) genotypes
      from sediments in which the pore-water salinity was close to that of sea water.
      All previously reported haloarchaeal isolates are obligate extreme halophiles
      requiring at least 9% (w/v) NaCl for growth and are typically the dominant
      heterotrophic organisms in salt and soda lakes, salt deposits and salterns. Two
      of these three newly isolated genotypes have lower requirements for salt than
      previously cultured haloarchaea and are capable of slow growth at sea-water
      salinity (2.5% w/v NaCl). Our data reveal the existence of Archaea that can grow
      in non-extreme conditions and of a diverse community of haloarchaea existing in
      coastal salt marsh sediments. Our findings suggest that the ecological range of
      these physiologically versatile prokaryotes is much wider than previously
      supposed.

PMID- 15142248
TI  - Graphite electrodes as electron donors for anaerobic respiration.
AB  - It has been demonstrated previously that Geobacter species can transfer electrons
      directly to electrodes. In order to determine whether electrodes could serve as
      electron donors for microbial respiration, enrichment cultures were established
      from a sediment inoculum with a potentiostat-poised graphite electrode as the
      sole electron donor and nitrate as the electron acceptor. Nitrate was reduced to
      nitrite with the consumption of electrical current. The stoichiometry of electron
      and nitrate consumption and nitrite accumulation were consistent with the
      electrode serving as the sole electron donor for nitrate reduction. Analysis of
      16 rRNA gene sequences demonstrated that the electrodes supplied with current
      were specifically enriched in microorganisms with sequences most closely related
      to the sequences of known Geobacter species. A pure culture of Geobacter
      metallireducens was shown to reduce nitrate to nitrite with the electrode as the
      sole electron donor with the expected stoichiometry of electron consumption.
      Cells attached to the electrode appeared to be responsible for the nitrate
      reduction. Attached cells of Geobacter sulfurreducens reduced fumarate to
      succinate with the electrode as an electron donor. These results demonstrate for
      the first time that electrodes may serve as a direct electron donor for anaerobic
      respiration. This finding has implications for the harvesting of electricity from
      anaerobic sediments and the bioremediation of oxidized contaminants.

PMID- 15142249
TI  - Pseudomonas putida mutants in the exbBexbDtonB gene cluster are hypersensitive to
      environmental and chemical stressors.
AB  - The genes in the exbBexbDtonB cluster of Pseudomonas putida DOT-T1E are co
      transcribed. We have generated non-polar mutants in each of the genes by
      inserting an aphA3 cassette encoding kanamycin resistance. All three mutants show
      similar phenotypes: the mutants are unable to grow on minimal medium under iron
      deficiency conditions. Furthermore, regardless of iron conditions, all mutants
      are hypersensitive to antibiotics, p-hydroxybenzoate and toluene, chemicals that
      are extruded from the cell by efflux pumps. These findings are discussed in terms
      of the involvement of the TonB system in the energization of outer membrane
      functions necessary for the import or export of different compounds in P. putida.

PMID- 15142250
TI  - Lentisphaera araneosa gen. nov., sp. nov, a transparent exopolymer producing
      marine bacterium, and the description of a novel bacterial phylum, Lentisphaerae.
AB  - Two phylogenetically distinct marine strains producing transparent exopolymers
      (TEP), designated HTCC2155(T) and HTCC2160, were cultivated from Oregon coast
      seawater by dilution to extinction in a high throughput culturing format. When
      cultured in low-nutrient seawater media, these strains copiously produced Alcian
      Blue-stainable viscous TEP. Growing cells were attached to each other by the TEP
      in a three dimensional network. Polymerase chain reaction employing 16S rDNA
      primers specific for the novel isolates indicated that they are indigenous to the
      water column of the Atlantic and Pacific oceans. The abundance of the isolates as
      determined by 16S rRNA dot blots, however, indicated that they are less than 1%
      of the total bacterial community. In phylogenetic analyses, the strains
      consistently formed a new phylum-level lineage within the domain Bacteria,
      together with members of the candidate phylum VadinBE97, which consists of
      Victivallis, the first cultured genus in the candidate phylum, and 16S rRNA gene
      clones from DNA extracted from marine or anaerobic terrestrial habitats. Five
      putative subgroups were delineated within this phylum-level lineage, including a
      marine group and an anaerobic group. The isolates are Gram negative, strictly
      aerobic, chemoheterotrophic, and facultatively oligotrophic sphere-shaped
      bacteria. The DNA G+C content of strain HTCC2155(T) was 48.3 mol% and the genome
      size was 2.9 mb. It is proposed from these observations that the strains be
      placed into a new genus and a new species named Lentisphaera araneosa (type
      strain HTCC2155(T) = ATCC BAA-859(T) = KCTC 12141(T)) gen. nov., sp. nov., the
      cultured marine representative of the Lentisphaerae phyl. nov., and the phylum be
      divided into two novel orders named the Lentisphaerales ord. nov. and the
      Victivallales ord. nov.

PMID- 15142251
TI  - Vertical and temporal shifts in microbial communities in the water column and
      sediment of saline meromictic Lake Kaiike (Japan), as determined by a 16S rDNA
      based analysis, and related to physicochemical gradients.
AB  - The vertical and temporal changes in microbial communities were investigated
      throughout the water column and sediment of the saline meromictic Lake Kaiike by
      PCR-denaturing gradient gel electrophoresis (DGGE) of 16S rDNA. Marked depth
      related changes in microbial communities were observed at the chemocline and the
      sediment-water interface. However, no major temporal changes in the microbial
      community below the chemocline were observed during the sampling period,
      suggesting that the ecosystem in the anoxic zone of Lake Kaiike was nearly
      stable. Although the sequence of the most conspicuous DGGE band throughout the
      anoxic water and in the top of the microbial mat was most similar to that of an
      anoxic, photosynthetic, green sulphur bacterium, Pelodyction luteolum DSM273 (97%
      similarity), it represented a new phylotype. A comparison of DGGE banding
      patterns of the water column and sediment samples demonstrated that specific
      bacteria accumulated on the bottom from the anoxic water layers, and that
      indigenous microbial populations were present in the sediment. The measurements
      of bicarbonate assimilation rates showed significant phototrophic assimilation in
      the chemocline and lithoautotrophic assimilation throughout the anoxic water, but
      were not clearly linked with net sulphide turnover rates, indicating that sulphur
      and carbon metabolisms were not directly correlated.

PMID- 15142252
TI  - Application and validation of DNA microarrays for the 16S rRNA-based analysis of
      marine bacterioplankton.
AB  - An oligonucleotide probe-based DNA microarray was evaluated for its ability to
      detect 16S rRNA targets in marine bacterioplankton samples without prior
      amplification by polymerase chain reaction (PCR). The results obtained were
      compared with those of quantitative fluorescence in situ hybridization (FISH).
      For extraction and direct labelling of total RNA, a fast and efficient protocol
      based on commercially available kits was established. A set of redundant and
      hierarchically structured probes was applied, and specificity of hybridization
      was assessed by additional control oligonucleotides comprising single central
      mismatches. The protocol was initially tested by microarray analysis of bacterial
      pure cultures. Complete discrimination of all control oligonucleotides was
      achieved, indicating a high degree of hybridization specificity. In a co-culture,
      abundant members were detected by microarray analysis, but signal ratios of
      positive probes did not correlate well with quantitative data from FISH
      experiments. A marine picoplankton sample from the German Bight was analysed.
      Bacterial populations with relative abundances of at least 5% were detected by
      hybridizing 0.1 microg of total RNA extracted from a sample of 375 ml equivalent
      to 4.1 x 10(8) cells. Our results demonstrate that major populations of marine
      bacterioplankton can be identified by microarray analysis in a fast and reliable
      way, even in relatively low volumes of sea water.

PMID- 15142253
TI  - Hydrogen threshold concentrations in pure cultures of halorespiring bacteria and
      at a site polluted with chlorinated ethenes.
AB  - Halorespiring microorganisms are not only able to oxidize organic electron donors
      such as formate, acetate, pyruvate and lactate, but also H(2). Because these
      microorganisms have a high affinity for H(2), this may be the most important
      electron donor for halorespiration in the environment. We have studied the role
      of H(2)-threshold concentrations in pure halorespiring cultures and compared them
      with mixed cultures and field data. We have found H(2)-threshold values between
      0.05 and 0.08 nM for Sulfurospirillum halorespirans, S. multivorans and
      Dehalobacter restrictus under PCE-reducing and nitrate-reducing conditions. The
      reduction of PCE and TCE can proceed at H(2) concentrations of below 1 nM at a
      polluted site. However, for the reduction of lower chlorinated ethenes a higher
      H(2) concentration is required. This indicates that the measured H(2)
      concentration in situ can be an indicator of the extent of anaerobic reductive
      dechlorination.

PMID- 15142257
TI  - Chemokine blockade: a new era in the treatment of rheumatoid arthritis?
AB  - Blockade of chemokines or chemokine receptors is emerging as a new potential
      treatment for various immune-mediated conditions. This review focuses on the
      therapeutic potential in rheumatoid arthritis, based on studies in animal models
      and patients. Several knockout models as well as in vivo use of chemokine
      antagonists are discussed. Review of these data suggests that this approach might
      lead to novel therapeutic strategies in rheumatoid arthritis and other chronic
      inflammatory disorders.

PMID- 15142256
TI  - Polyphosphoinositides-dependent regulation of the osteoclast actin cytoskeleton
      and bone resorption.
AB  - BACKGROUND: Gelsolin, an actin capping protein of osteoclast podosomes, has a
      unique function in regulating assembly and disassembly of the podosome actin
      filament. Previously, we have reported that osteopontin (OPN) binding to integrin
      alphavbeta3 increased the levels of gelsolin-associated polyphosphoinositides,
      podosome assembly/disassembly, and actin filament formation. The present study
      was undertaken to identify the possible role of polyphosphoinositides and
      phosphoinositides binding domains (PBDs) of gelsolin in the osteoclast
      cytoskeletal structural organization and osteoclast function. RESULTS:
      Transduction of TAT/full-length gelsolin and PBDs containing gelsolin peptides
      into osteoclasts demonstrated: 1) F-actin enriched patches; 2) disruption of
      actin ring; 3) an increase in the association polyphosphoinositides (PPIs) with
      the transduced peptides containing PBDs. The above-mentioned effects were more
      pronounced with gelsolin peptide containing 2 tandem repeats of PBDs (PBD (2)).
      Binding of PPIs to the transduced peptides has resulted in reduced levels of PPIs
      association with the endogenous gelsolin, and thereby disrupted the actin
      remodeling processes in terms of podosome organization in the clear zone area and
      actin ring formation. These peptides also exhibited a dominant negative effect in
      the formation of WASP-Arp2/3 complex indicating the role of phosphoinositides in
      WASP activation. The TAT-PBD gelsolin peptides transduced osteoclasts are
      functionally defective in terms of motility and bone resorption. CONCLUSIONS:
      Taken together, these data demonstrate that transduction of PBD gelsolin peptides
      into osteoclasts produced a dominant negative effect on actin assembly, motility,
      and bone resorption. These findings indicate that phosphoinositide-mediated
      signaling mechanisms regulate osteoclast cytoskeleton, podosome
      assembly/disassembly, actin ring formation and bone resorption activity of
      osteoclasts.

PMID- 15142259
TI  - Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis.
AB  - Antibodies directed to citrullinated proteins (e.g. anti-CCP [cyclic
      citrullinated peptide] antibodies) are highly specific for rheumatoid arthritis
      (RA). These antibodies are produced at the site of inflammation in RA, and
      therefore citrullinated antigens are also expected to be present in the inflamed
      synovium. We discuss literature showing that the presence of citrullinated
      proteins in the synovium is not specific for RA. The RA-specific antibodies are
      therefore most likely the result of an abnormal immune response that specifically
      occurs in RA patients. It was recently shown that presence of anti-CCP antibodies
      precedes the onset of clinical symptoms of RA by years. It thus appears that it
      may take years for initial events that cause the generation of anti-CCP
      antibodies to develop into full-blown disease.

PMID- 15142258
TI  - Psychological stress and fibromyalgia: a review of the evidence suggesting a
      neuroendocrine link.
AB  - The present review attempts to reconcile the dichotomy that exists in the
      literature in relation to fibromyalgia, in that it is considered either a somatic
      response to psychological stress or a distinct organically based syndrome.
      Specifically, the hypothesis explored is that the link between chronic stress and
      the subsequent development of fibromyalgia can be explained by one or more
      abnormalities in neuroendocrine function. There are several such abnormalities
      recognised that both occur as a result of chronic stress and are observed in
      fibromyalgia. Whether such abnormalities have an aetiologic role remains
      uncertain but should be testable by well-designed prospective studies.

PMID- 15142260
TI  - Altered signalling thresholds in T lymphocytes cause autoimmune arthritis.
AB  - The development of spontaneous autoimmunity in inbred strains of rodents has
      allowed us to investigate the molecular basis of chronic inflammatory disease in
      ways that would not be possible in humans. Recently, two new mouse models of
      autoimmune inflammatory polyarthritis have been reported that demonstrate how
      alterations in signalling thresholds sufficient to perturb central T-cell
      tolerance lead to inflammatory arthritis. These mice provide new insights into
      the complexities of what may turn out to be a heterogeneous group of diseases
      that we call rheumatoid arthritis. They will also provide unique tools for
      dissecting precisely how chronically activated T cells contribute to the effector
      phase of arthritis through mechanisms that may be less dependent on antigen
      receptor signalling.

PMID- 15142261
TI  - A surplus of positive trials: weighing biases and reconsidering equipoise.
AB  - In this issue, Fries and Krishnan raise provocative new ideas to explain the
      surfeit of positive industry sponsored trials evaluating new drugs. They suggest
      that these trials were designed after so much preliminary work that they were
      bound to be positive (design bias) and that this violates clinical equipoise,
      which they characterize as an antiquated concept that should be replaced by a
      focus on subject autonomy in decision making and expected value for all
      treatments in a trial. We contend that publication bias, more than design bias,
      could account for the remarkably high prevalence of positive presented trials.
      Furthermore, even if all new drugs were efficacious, given the likelihood of type
      2 errors, not all trials would be positive. We also suggest that clinical
      equipoise is a nuanced concept dependent on the existence of controversy about
      the relative value of two treatments being compared. If there were no
      controversy, then trials would be both unnecessary and unethical. The proposed
      idea of positive expected value is intriguing, but in the real world such clearly
      determinable values do not exist. Neither is it clear how investigators and
      sponsors, who are invested in the success of a proposed therapy, would (or
      whether they should) develop such a formula.

PMID- 15142262
TI  - Gene expression signatures for autoimmune disease in peripheral blood mononuclear
      cells.
AB  - The relatively new technology of DNA microarrays offers the possibility to probe
      the human genome for clues to the pathogenesis and treatment of human disease.
      While early studies using this approach were largely in oncology, many new
      reports are emerging in other fields including infectious diseases and
      pharmacology, and applications in autoimmunity have been recently reported by our
      group and others. Some of these investigations have examined animal models of
      autoimmune disease, but a number of human studies have also been carried out. Of
      special interest are those that have used peripheral blood samples because,
      unlike tissue biopsies, these are readily available from all subjects. Using this
      approach, patterns of gene expression can be detected that distinguish patients
      with autoimmune conditions from normal subjects. Furthermore, the genes that are
      identified provide clues to possible pathogenetic mechanisms and are likely to be
      useful in developing tests to establish diagnostic categories and predict
      therapeutic responses.

PMID- 15142263
TI  - The active metabolite of leflunomide, A77 1726, increases the production of IL-1
      receptor antagonist in human synovial fibroblasts and articular chondrocytes.
AB  - Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid
      arthritis. In this study, we investigated the effect of A77 1726 - the active
      metabolite of leflunomide - on the production of IL-1 receptor antagonist (IL
      1Ra) by human synovial fibroblasts and articular chondrocytes. Cells were
      incubated with A77 1726 alone or in combination with proinflammatory cytokines.
      IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in
      the presence of IL-1beta or tumour necrosis factor-alpha it markedly enhanced the
      secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77
      1726 was greatest at 100 micromol/l. In synovial fibroblasts and de
      differentiated chondrocytes, A77 1726 also increased IL-1beta-induced IL-1Ra
      production in cell lysates. Freshly isolated chondrocytes contained no
      significant amounts of intracellular IL-1Ra. A77 1726 is a known inhibitor of
      pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous
      uridine did not significantly modify the effect of A77 1726 on IL-1Ra production,
      suggesting that it was not mediated by inhibition of pyrimidine synthesis.
      Indomethacin increased IL-1beta-induced IL-1Ra secretion in synovial fibroblasts
      and de-differentiated chondrocytes, suggesting that inhibition of COX-2 may
      indeed enhance IL-1beta-induced IL-1Ra production. However, the stimulatory
      effect of indomethacin was consistently less effective than that of A77 1726. A77
      1726 increases IL-1Ra production by synovial fibroblasts and chondrocytes in the
      presence of proinflammatory cytokines, and thus it may possess chondroprotective
      effects. The effect of A77 1726 may be partially mediated by inhibition of COX-2,
      but other mechanisms likely concur to stimulate IL-1Ra production.

PMID- 15142264
TI  - Increased AP-1 and NF-kappaB activation and recruitment with the combination of
      the proinflammatory cytokines IL-1beta, tumor necrosis factor alpha and IL-17 in
      rheumatoid synoviocytes.
AB  - To determine the contribution of IL-1beta, tumor necrosis factor alpha (TNF
      alpha) and IL-17 to AP-1, NF-kappaB and Egr-1 activation in rheumatoid arthritis,
      the effect of the cytokines used alone or in combination was measured on TF
      expression in rheumatoid synoviocytes. Effects on mRNA expression were measured
      by RT-PCR and effects on nuclear translocation were measured by
      immunocytochemistry. To assess the functional consequences of cytokine induction,
      osteoprotegerin levels were measured in synoviocyte supernatants.IL-1beta and TNF
      alpha alone at optimal concentration (100 pg/ml) induced the nuclear
      translocation of NF-kappaB and almost all AP-1 members, except JunB and Egr-1 for
      IL-1beta and except Fra-2 and Egr-1 for TNF-alpha. IL-17 was clearly less potent
      since no nuclear translocation was observed, except for a weak activation of Fra
      1 and NF-kappaB. More importantly, when these cytokines were used at low
      concentrations, their combination showed a synergistic effect on almost all the
      TFs, except for Egr-1, with a particular effect on Fra-1 and NF-kappaB. Increased
      recruitment of additional factors was induced when the three cytokines were
      combined. IL-1 and TNF-alpha induced mRNA expression of c-jun while IL-17 had no
      effect. A synergistic effect was seen with their combination. A similar
      synergistic effect was observed for osteoprotegerin production when these three
      cytokines were combined at low concentrations.AP-1 and NF-kappaB pathways were
      highly sensitive to the combination through synergistic mechanisms. These effects
      observed in rheumatoid arthritis synoviocytes may reflect the conditions found in
      the rheumatoid arthritis joint and may contribute to the mode of action of
      cytokine inhibitors.

PMID- 15142265
TI  - Association of a specific haplotype across the genes MMP1 and MMP3 with
      radiographic joint destruction in rheumatoid arthritis.
AB  - The genetic background of rheumatoid arthritis (RA) is only partly understood,
      and several genes seem to be involved. The matrix metalloproteinases MMP1
      (interstitial collagenase) and MMP3 (stromelysin 1) are thought to be important
      in destructive joint changes seen in RA. In the present study, functional
      relevant promoter polymorphisms of MMP1 and MMP3 were genotyped in 308 patients
      and in 110 controls, to test whether the polymorphisms contribute to the severity
      of the disease measured by radiographic progression of joint destruction. For
      comparison, the shared epitope of HLA DR4 and DR1 (SE) was determined by
      polymerase chain reaction. There was no association of MMP polymorphisms with
      susceptibility to RA. However, a strong linkage disequilibrium was observed
      between the 1G/2G (MMP1) and the 5A/6A (MMP3) polymorphisms (P << 10(-6); linkage
      disequilibrium index D' = 0.46). In factorial regression, the degree of
      radiographic joint destruction correlated significantly with the 1G-5A haplotype
      (P = 0.0001) and the interaction term 'estimated number of 1G-5A haplotypes x
      duration of disease' (P = 0.0007). This association was phasic, indicating that
      possession of the 1G-5A haplotype has a protective effect over a period of about
      15 years of RA, but might be associated with a more pronounced radiographic
      progression later on. Similar results were also found with the 1G allele of MMP1
      alone (P = 0.015) and with the interaction term 'estimated number of 1G alleles x
      duration of disease' (P = 0.014). The correlation of SE with the Ratingen score
      was comparable (0.044). The regression model of MMP haplotypes explained 35% of
      the variance of the radiographic score, whereas the SE explained 29%. The 1G-5A
      haplotype across the closely linked MMP1 and MMP3 gene loci is a newly described
      genetic factor strongly associated with the progression of joint damage in RA.
      Our findings suggest that there are haplotypes in a MMP cluster region that
      modify the joint destruction in RA in a phasic manner.

PMID- 15142266
TI  - Relationship between radiographic grading of osteoarthritis and the biochemical
      markers for arthritis in knee osteoarthritis.
AB  - The aim of this study was to investigate the relationship between the biochemical
      markers of arthritis and the radiographic grading of osteoarthritis (OA) in
      knees. Seventy-one women aged 49-85 years with knee OA were studied. Anterior
      posterior knee radiographs and hand radiographs were taken in all patients. The
      radiographic grading of OA in the knee was performed by using the Kellgren
      Lawrence criteria and the joint space width. The 71 patients with knee OA were
      divided into two groups: 37 patients exhibiting generalized osteoarthritis (GOA)
      and 34 non-GOA patients, according to the grading of their hand radiograph. C
      reactive protein (CRP), urinary pyridinoline, YKL-40, plasma matrix
      metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases
      (TIMP)-1 were measured as the biochemical markers of arthritis. The radiographic
      grading with the Kellgren-Lawrence scale revealed a significant relationship to
      the joint space width (P = 0.003): the joint space width decreased with
      increasing Kellgren-Lawrence grade. All biochemical markers had negative
      correlations with the joint space width, but only urinary pyridinoline had a
      significant correlation (P = 0.039). Pyridinoline (P = 0.034) and TIMP-1 (P =
      0.017) also exhibited a significant relationship to the Kellgren-Lawrence grade.
      In GOA evaluations, the joint space width did not differ between GOA and non-GOA
      patients. CRP, pyridinoline, YKL-40 and MMP-3 levels were significantly greater
      in GOA patients than in non-GOA patients. CRP, pyridinoline, YKL-40, MMP-3 and
      TIMP-1 levels each related to at least one of the radiographic gradings.
      Furthermore, pyridinoline related to every type of radiographic grading examined
      in the present study.

PMID- 15142267
TI  - Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen
      induced arthritis by oral administration of type II collagen.
AB  - Induction of oral tolerance has long been considered a promising approach to the
      treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA).
      Oral administration of type II collagen (CII) has been proven to improve signs
      and symptoms in RA patients without troublesome toxicity. To investigate the
      mechanism of immune suppression mediated by orally administered antigen, we
      examined changes in serum IgG subtypes and T-cell proliferative responses to CII,
      and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of
      collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice
      peaked at 5 weeks after primary immunization with CII, which was significantly
      less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice
      that had been fed with CII also exhibited increased serum IgG1 and decreased
      serum IgG2a as compared with nontolerized CIA animals. The T-cell proliferative
      response to CII was suppressed in lymph nodes of tolerized mice also. Production
      of IL-10 and of transforming growth factor-beta from mononuclear lymphocytes was
      increased in the tolerized animals, and CD4+ T cells isolated from tolerized mice
      did not respond with induction of IFN-gamma when stimulated in vitro with CII. We
      also observed greater induction of IL-10-producing CD4+CD25+ subsets among CII
      stimulated splenic T cells from tolerized mice. These data suggest that when
      these IL-10-producing CD4+CD25+ T cells encounter CII antigen in affected joints
      they become activated to exert an anti-inflammatory effect.

PMID- 15142268
TI  - Enhanced osteoclast development in collagen-induced arthritis in interferon-gamma
      receptor knock-out mice as related to increased splenic CD11b+ myelopoiesis.
AB  - Collagen-induced arthritis (CIA) in mice is accompanied by splenomegaly due to
      the selective expansion of immature CD11b+ myeloblasts. Both disease
      manifestations are more pronounced in interferon-gamma receptor knock-out (IFN
      gammaR KO) mice. We have taken advantage of this difference to test the
      hypothesis that the expanding CD11b+ splenic cell population constitutes a source
      from which osteoclast precursors are recruited to the joint synovia. We found
      larger numbers of osteoclasts and more severe bone destruction in joints of IFN
      gammaR KO mice than in joints of wild-type mice. Osteoclast-like multinucleated
      cells appeared in splenocyte cultures established in the presence of macrophage
      colony-stimulating factor (M-CSF) and stimulated with the osteoclast
      differentiating factor receptor activator of NF-kappaB ligand (RANKL) or with
      tumour necrosis factor-alpha (TNF-alpha). Significantly larger numbers of such
      cells could be generated from splenocytes of IFN-gammaR KO mice than from those
      of wild-type mice. This was not accompanied, as might have been expected, by
      increased concentrations of the intracellular adaptor protein TRAF6, known to be
      involved in signalling of RANKL- and TNF-alpha-induced osteoclast formation.
      Splenocyte cultures of IFN-gammaR KO mice also produced more TNF-alpha and more
      RANKL than those of wild-type mice. Finally, splenocytes isolated from immunised
      IFN-gammaR KO mice contained comparatively low levels of pro-interleukin-1beta
      (pro-IL-1beta) and pro-caspase-1, indicating more extensive conversion of pro-IL
      1beta into secreted active IL-1beta. These observations provide evidence that all
      conditions are fulfilled for the expanding CD11b+ splenocytes to act as a source
      of osteoclasts and to be indirectly responsible for bone destruction in CIA. They
      also provide a plausible explanation for the higher susceptibility of IFN-gammaR
      KO mice to CIA.

PMID- 15142269
TI  - Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase
      women with fibromyalgia and chronic fatigue syndrome and effect of depressive
      symptoms on these hormones.
AB  - We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and
      cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome
      (CFS) who were in the follicular phase of their menstrual cycle, and whether
      their scores for depressive symptoms were related to levels of these hormones. A
      total of 176 subjects participated - 46 healthy volunteers, 68 patients with
      fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle
      stimulating hormone, luteinizing hormone (LH), estradiol, progesterone,
      prolactin, and cortisol. Depressive symptoms were assessed using the Beck
      Depression Inventory (BDI). Cortisol levels were significantly lower in patients
      with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no
      significant differences in other hormone levels between the three groups.
      Fibromyalgia patients with high BDI scores had significantly lower cortisol
      levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI
      scores (P < 0.05). Among patients without depressive symptoms, cortisol levels
      were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in
      spite of low morning cortisol concentrations, the only abnormalities in
      hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with
      fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low
      BDI score. Depression may lower cortisol and LH levels, or, alternatively, low
      morning cortisol may be a biological factor that contributes to depressive
      symptoms in fibromyalgia. These parameters therefore must be taken into account
      in future investigations.

PMID- 15142270
TI  - Treatment with recombinant interferon-beta reduces inflammation and slows
      cartilage destruction in the collagen-induced arthritis model of rheumatoid
      arthritis.
AB  - We investigated the therapeutic potential and mechanism of action of IFN-beta
      protein for the treatment of rheumatoid arthritis (RA). Collagen-induced
      arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice
      were given daily injections of recombinant mouse IFN-beta or saline for 7 days.
      Disease progression was monitored by visual clinical scoring and measurement of
      paw swelling. Inflammation and joint destruction were assessed histologically 8
      days after the onset of arthritis. Proteoglycan depletion was determined by
      safranin O staining. Expression of cytokines, receptor activator of NF-kappaB
      ligand, and c-Fos was evaluated immunohistochemically. The IL-1-induced
      expression of IL-6, IL-8, and granulocyte/macrophage-colony-stimulating factor
      (GM-CSF) was studied by ELISA in supernatant of RA and osteoarthritis fibroblast
      like synoviocytes incubated with IFN-beta. We also examined the effect of IFN
      beta on NF-kappaB activity. IFN-beta, at 0.25 microg/injection and higher,
      significantly reduced disease severity in two experiments, each using 8-10 mice
      per treatment group. IFN-beta-treated animals displayed significantly less
      cartilage and bone destruction than controls, paralleled by a decreased number of
      positive cells of two gene products required for osteoclastogenesis, receptor
      activator of NF-kappaB ligand and c-Fos. Tumor necrosis factor alpha and IL-6
      expression were significantly reduced, while IL-10 production was increased after
      IFN-beta treatment. IFN-beta reduced expression of IL-6, IL-8, and GM-CSF in RA
      and osteoarthritis fibroblast-like synoviocytes, correlating with reduced NF
      kappaB activity. The data support the view that IFN-beta is a potential therapy
      for RA that might help to diminish both joint inflammation and destruction by
      cytokine modulation.

PMID- 15142271
TI  - Equipoise, design bias, and randomized controlled trials: the elusive ethics of
      new drug development.
AB  - The concept of 'equipoise', or the 'uncertainty principle', has been represented
      as a central ethical principle, and holds that a subject may be enrolled in a
      randomized controlled trial (RCT) only if there is true uncertainty about which
      of the trial arms is most likely to benefit the patient. We sought to estimate
      the frequency with which equipoise conditions were met in industry-sponsored RCTs
      in rheumatology, to explore the reasons for any deviations from equipoise, to
      examine the concept of 'design bias', and to consider alternative ethical
      formulations that might improve subject safety and autonomy. We studied abstracts
      accepted for the 2001 American College of Rheumatology meetings that reported
      RCTs, acknowledged industry sponsorship, and had clinical end-points (n = 45),
      and examined the proportion of studies that favored the registration or marketing
      of the sponsor's drug. In every trial (45/45) results were favorable to the
      sponsor, indicating that results could have been predicted in advance solely by
      knowledge of sponsorship (P < 0.0001). Equipoise clearly was being systematically
      violated. Publication bias appeared to be an incomplete explanation for this
      dramatic result; this bias occurs after a study is completed. Rather, we
      hypothesize that 'design bias', in which extensive preliminary data are used to
      design studies with a high likelihood of being positive, is the major cause of
      the asymmetric results. Design 'bias' occurs before the trial is begun and is
      inconsistent with the equipoise principle. However, design bias increases
      scientific efficiency, decreases drug development costs, and limits the number of
      subjects required, probably reducing aggregate risks to participants. Conceptual
      and ethical issues were found with the equipoise principle, which encourages
      performance of negative studies; ignores patient values, patient autonomy, and
      social benefits; is applied at a conceptually inappropriate decision point (after
      randomization rather than before); and is in conflict with the Belmont,
      Nuremberg, and other sets of ethical principles, as well as with US Food and Drug
      Administration procedures. We propose a principle of 'positive expected
      outcomes', which informs the assessment that a trial is ethical, together with a
      restatement of the priority of personal autonomy.

PMID- 15142272
TI  - Delayed resolution of acute inflammation during zymosan-induced arthritis in
      leptin-deficient mice.
AB  - The severity of antigen-induced arthritis (AIA) is decreased in leptin-deficient
      ob/ob mice. However, joint inflammation in AIA depends on the immune response,
      which is impaired in ob/ob mice. In the present study we investigated the effects
      of leptin deficiency on zymosan-induced arthritis (ZIA), which is independent of
      adaptive immunity. Arthritis was induced by injection of zymosan into the knee
      joint. Joint swelling was similar after 6 and 24 hours in ob/ob and control mice.
      However, it remained elevated in ob/ob animals on day 3 whereas values normalized
      in controls. Histology revealed similar articular lesions in all animals on day
      3, but on days 14 and 21 arthritis tended to be more severe in ob/ob mice. The
      acute phase response, reflected by circulating levels of IL-6 and serum amyloid
      A, was also more pronounced in ob/ob mice, although corticosterone was
      significantly elevated in these animals. Similar results were obtained in leptin
      receptor-deficient db/db mice. Thus, in contrast to AIA, ZIA is not impaired in
      leptin-deficient animals. On the contrary, resolution of acute inflammation
      appears to be delayed in the absence of leptin or leptin signalling, suggesting
      that chronic leptin deficiency interferes with adequate control of the
      inflammatory response in ZIA.

PMID- 15142273
TI  - Autoantibody profile in rheumatoid arthritis during long-term infliximab
      treatment.
AB  - The aim of the present study was to investigate the effect of long-term
      infliximab treatment on various autoantibodies in patients with rheumatoid
      arthritis. Serum samples from 30 consecutive patients, who were prospectively
      followed during infliximab and methotrexate therapy for refractory rheumatoid
      arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these
      points, median values of the Disease Activity Score were 6.38 (interquartile
      range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06),
      respectively. Various autoantibodies were assessed by standard indirect
      immunofluorescence and/or ELISA. Initially, 50% of patients were positive for
      antinuclear antibodies, and this figure increased to 80% after 78 weeks (P =
      0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin
      antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by
      ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at
      78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The
      proportion of patients who were positive for rheumatoid factor (RF) was similar
      at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF
      titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47
      290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP)
      antibodies were found in 83% of patients before therapy; anti-CCP antibody titre
      significantly decreased at 30 weeks but returned to baseline thereafter. In
      conclusion, the presence of anti-double-stranded DNA antibodies is a transient
      phenomenon, despite a stable increase in antinuclear and anticardiolipin
      antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres
      differed during long-term infliximab therapy.

PMID- 15142276
TI  - A gastrointestinal stromal tumor (GIST) masquerading as an ovarian mass.
AB  - BACKGROUND: Malignant gastrointestinal stromal tumors (GIST) are rare mesenchymal
      tumors originating in the wall of the gastrointestinal tract. Myogenic
      gastrointestinal stromal tumor, a distinctive morphologic variant is
      characterized by an unusually prominent myxoid stromal background. CASE
      PRESENTATION: We report a case of myxoid variant of GIST in a 42 years old woman
      presenting as an epigastric mass associated to an ovarian cyst and elevated CA
      125. Histologically, the lesions was composed of a proliferation of spindle cells
      in an abundant myxoid stroma, without evidence of atypia or anaplasia.
      Immunohistochemical stains showed strong positive staining with muscle actin,
      positive staining with CD34 and weak positive staining with CD117, while showed
      negative for S-100. CONCLUSION: At surgery every effort should be made to
      identify the origin of the tumor. A complete surgical removal of the tumor should
      be obtained, as this is the only established treatment that offers long term
      survival.

PMID- 15142275
TI  - Effect of phospholipase A2 inhibitory peptide on inflammatory arthritis in a TNF
      transgenic mouse model: a time-course ultrastructural study.
AB  - We evaluated the therapeutic effect of secretory phospholipase A2 (sPLA2)
      inhibitory peptide at a cellular level on joint erosion, cartilage destruction,
      and synovitis in the human tumor necrosis factor (TNF) transgenic mouse model of
      arthritis. Tg197 mice (N = 18) or wild-type (N = 10) mice at 4 weeks of age were
      given intraperitoneal doses (7.5 mg/kg) of a selective sPLA2 inhibitory peptide,
      P-NT.II, or a scrambled P-NT.II (negative control), three times a week for 4
      weeks. Untreated Tg197 mice (N = 10) were included as controls. Pathogenesis was
      monitored weekly for 4 weeks by use of an arthritis score and histologic
      examinations. Histopathologic analysis revealed a significant reduction after P
      NT.II treatment in synovitis, bone erosion, and cartilage destruction in
      particular. Conspicuous ultrastructural alterations seen in articular
      chondrocytes (vacuolated cytoplasm and loss of nuclei) and synoviocytes
      (disintegrating nuclei and vacuoles, synovial adhesions) of untreated or
      scrambled-P-NT.II-treated Tg197 mice were absent in the P-NT.II-treated Tg197
      group. Histologic scoring and ultrastructural evidence suggest that the
      chondrocyte appears to be the target cell mainly protected by the peptide during
      arthritis progression in the TNF transgenic mouse model. This is the first time
      ultrastructural evaluation of this model has been presented. High levels of
      circulating sPLA2 detected in untreated Tg197 mice at age 8 weeks of age were
      reduced to basal levels by the peptide treatment. Attenuation of
      lipopolysaccharide- and TNF-induced release of prostaglandin E2 from cultured
      macrophage cells by P-NT.II suggests that the peptide may influence the
      prostaglandin-mediated inflammatory response in rheumatoid arthritis by limiting
      the bioavailability of arachidonic acid through sPLA2 inhibition.

PMID- 15142274
TI  - CD14 mediates the innate immune responses to arthritopathogenic peptidoglycan
      polysaccharide complexes of Gram-positive bacterial cell walls.
AB  - Bacterial infections play an important role in the multifactorial etiology of
      rheumatoid arthritis. The arthropathic properties of Gram-positive bacteria have
      been associated with peptidoglycan-polysaccharide complexes (PG-PS), which are
      major structural components of bacterial cell walls. There is little agreement as
      to the identity of cellular receptors that mediate innate immune responses to PG
      PS. A glycosylphosphatidylinositol-linked cell surface protein, CD14, the
      lipopolysaccharide receptor, has been proposed as a PG-PS receptor, but
      contradictory data have been reported. Here, we examined the inflammatory and
      pathogenic responses to PG-PS in CD14 knockout mice in order to examine the role
      for CD14 in PG-PS-induced signaling. We found that PG-PS-induced responses in
      vitro, including transient increase in intracellular calcium, activation of
      nuclear factor-kappaB, and secretion of the cytokines tumor necrosis factor-alpha
      and interleukin-6, were all strongly inhibited in CD14 knockout macrophages. In
      vivo, the incidence and severity of PG-PS induced acute polyarthritis were
      significantly reduced in CD14 knockout mice as compared with their wild-type
      counterparts. Consistent with these findings, CD14 knockout mice had
      significantly inhibited inflammatory cell infiltration and synovial hyperplasia,
      and reduced expression of inflammatory cytokines in PG-PS arthritic joints. These
      results support an essential role for CD14 in the innate immune responses to PG
      PS and indicate an important role for CD14 in PG-PS induced arthropathy.

PMID- 15142277
TI  - Testing the performance of the ENRICHD Social Support Instrument in cardiac
      patients.
AB  - BACKGROUND: Previous investigations suggest an important role of social support
      in the outcomes of patients treated for ischemic heart disease. The ENRICHD
      Social Support Instrument (ESSI) is a 7-item self-report survey that assesses
      social support. Validity and reliability of the ESSI, however, has not been
      formally tested in patients undergoing percutaneous coronary intervention (PCI).
      METHODS: The ESSI, along with the Short Form-36 (SF-36), was sequentially
      administered to a cohort of 271 patients undergoing PCI. The test-retest
      reliability was examined with an intra-class correlation coefficient by comparing
      scores among 174 patients who completed both instruments 5 and 6 months after
      their procedure. Internal reliability was assessed using Cronbach's alpha at the
      time of patients' baseline procedure. The concurrent validity of the ESSI was
      assessed by comparing scores between depressed (MHI-5 score < 44) vs. non
      depressed patients. The correlation between the ESSI and the SF-36 Social
      Functioning sub-scale, an accepted measure of social functioning, was also
      examined. RESULTS: Test-retest reliability showed no significant differences in
      mean scores among ESSI questionnaires administered 1 month apart (27.8+/-1.4 vs
      27.8+/-1.5, p = 0.98). The intra-class correlation coefficient was 0.94 and
      Cronbach's alpha was 0.88. Mean ESSI scores were significantly lower among
      depressed vs. non-depressed patients (24.6+/-1.7 vs 27+/-1.4, p < 0.018) and a
      positive albeit modest correlation with social functioning was seen (r = 0.19, p
      = 0.002). CONCLUSION: The ESSI appears to be a valid and reliable measure of
      social support in patients undergoing treatment for coronary artery disease. It
      may prove to be a valuable method of controlling for patient variability in
      outcomes studies where the outcomes are related to patients' social support.

PMID- 15142279
TI  - Trypanosoma rangeli Transcriptome Project: Generation and analysis of expressed
      sequence tags.
AB  - Trypanosoma rangeli is an important hemoflagellate parasite of several mammalian
      species in Central and South America, sharing geographical areas, vectors and
      reservoirs with T. cruzi, the causative agent of Chagas disease. Thus, the
      occurrence of single and/or mixed infections, including in humans, must be
      expected and are of great importance for specific diagnosis and epidemiology. In
      comparison to several Trypanosomatidae species, the T. rangeli biology and genome
      are little known, reinforcing the needs of a gene discovery initiative. The T.
      rangeli transcriptome initiative aims to promote gene discovery through the
      generation of expressed sequence tags (ESTs) and Orestes (ORF ESTs) from both
      epimastigote and trypomastigote forms of the parasite, allowing further studies
      of the parasite biology, taxonomy and phylogeny.

PMID- 15142278
TI  - Chagas' disease and AIDS.
AB  - Chagas' disease caused by Trypanosoma cruzi is an opportunistic infection in the
      setting of HIV/AIDS. Some individuals with HIV and chronic T. cruzi infection may
      experience a reactivation, which is most commonly manifested by
      meningoencephalitis. A reactivation myocarditis is the second most common
      manifestation. These presentations may be difficult to distinguish from
      toxoplasmosis in individuals with HIV/AIDS. The overlap of HIV and Trypanosoma
      cruzi infection occurs not only in endemic areas but also in non-endemic areas of
      North America and Europe where the diagnosis may be even more difficult. The
      pathological features, diagnosis and the role of cytokines in the pathogenesis of
      the disease are discussed.

PMID- 15142280
TI  - The Surgical Nosology In Primary-care Settings (SNIPS): a simple bridging
      classification for the interface between primary and specialist care.
AB  - BACKGROUND: The interface between primary care and specialist medical services is
      an important domain for health services research and policy. Of particular
      concern is optimising specialist services and the organisation of the specialist
      workforce to meet the needs and demands for specialist care, particularly those
      generated by referral from primary care. However, differences in the disease
      classification and reporting of the work of primary and specialist surgical
      sectors hamper such research. This paper describes the development of a bridging
      classification for use in the study of potential surgical problems in primary
      care settings, and for classifying referrals to surgical specialties. METHODS: A
      three stage process was undertaken, which involved: (1) defining the categories
      of surgical disorders from a specialist perspective that were relevant to the
      specialist-primary care interface; (2) classifying the 'terms' in the
      International Classification of Primary Care Version 2-Plus (ICPC-2 Plus) to the
      surgical categories; and (3) using referral data from 303,000 patient encounters
      in the BEACH study of general practice activity in Australia to define a core set
      of surgical conditions. Inclusion of terms was based on the probability of
      specialist referral of patients with such problems, and specialists' perception
      that they constitute part of normal surgical practice. RESULTS: A four-level
      hierarchy was developed, containing 8, 27 and 79 categories in the first, second
      and third levels, respectively. These categories classified 2050 ICPC-2 Plus
      terms that constituted the fourth level, and which covered the spectrum of
      problems that were managed in primary care and referred to surgical specialists.
      CONCLUSION: Our method of classifying terms from a primary care classification
      system to categories delineated by specialists should be applicable to research
      addressing the interface between primary and specialist care. By describing the
      process and putting the bridging classification system in the public domain, we
      invite comment and application in other settings where similar problems might be
      faced.

PMID- 15142282
TI  - Two sessions with Lawrence.

PMID- 15142281
TI  - NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification
      of a novel NAT1 allelic variant.
AB  - BACKGROUND: Alzheimer's disease is multifactorial, having environmental,
      toxicological and genetic risk factors. Impaired folate and homocysteine
      metabolism has been hypothesised to increase risk. In addition to its xenobiotic
      metabolising capacity, human arylamine N-acetyltransferase type-1 (NAT1)
      acetylates the folate catabolite para-aminobenzoylglutamate and is implicated in
      folate metabolism. The purpose of this study was to determine whether
      polymorphisms in the human NAT genes influence susceptibility to Alzheimer's
      disease. METHODS: Elderly individuals with and without Alzheimer's disease were
      genotyped at the polymorphic NAT1 (147 cases; 111 controls) and NAT2 (45 cases;
      63 controls) loci by polymerase chain reaction-restriction fragment length
      polymorphism, and the genotype and allele frequencies were compared using the chi
      squared test. RESULTS: Although a trend towards fast NAT2 acetylator-associated
      Alzheimer's disease susceptibility was indicated and the NAT1*10/1*10 genotype
      was observed only in cases of Alzheimer's disease (6/147, 4.1%), no significant
      difference in the frequency of NAT2 (p = 0.835) or NAT1 (p = 0.371) genotypes was
      observed between cases and controls. In addition, a novel NAT1 variant, NAT1*11B,
      was identified. CONCLUSIONS: These results suggest that genetic polymorphisms in
      NAT1 and NAT2 do not influence susceptibility to Alzheimer's disease, although
      the increase in frequency of the NAT1*10 allele in Alzheimer's disease is worthy
      of further investigation. Due to its similarity with the NAT1*11A allele,
      NAT1*11B is likely to encode an enzyme with reduced NAT1 activity.

PMID- 15142285
TI  - Gaze, dominance and humiliation in the Schreber case.
AB  - In this paper the author reviews Freud's study of Schreber's Memoirs and the
      Memoirs themselves from a perspective of nearly 100 years. He argues that
      Schreber's illness began as a melancholic depression but quickly developed
      paranoid features which subsequently escalated into a gross paranoia which
      nevertheless retained its depressive and hypochondriacal base. Finally the
      chaotic fragmentation became organized under the dominance of an omnipotent
      narcissistic organisation which led to a clinical improvement without any
      relinquishment of his delusional beliefs. As a subsidiary theme he examines the
      role of gaze in Schreber's object relations and argues that gaze was used to
      project into his objects, then to scrutinise the object to see if the projections
      had been received and tolerated, and finally as an expression of dominance. His
      urgent demand for relief provoked an omnipotence in his objects which he was then
      able triumphantly to frustrate and which ushered in a struggle over dominance in
      the course of which Schreber was abused and humiliated. He was unable to find an
      object who could contain his distress and these factors contributed to the
      failure to tolerate guilt and to work through his depression.

PMID- 15142286
TI  - An introduction to the reading of Bion.
AB  - The author suggests that a good deal of the confusion that arises in the course
      of reading Bion derives from the fact that Bion's analytic writing is comprised
      of two periods of work that involve markedly different conceptions of
      psychoanalysis. These two periods require of the reader very different ways of
      reading and generate contrasting experiences in reading. Bion, in passages in
      Learning from experience (1962) and Attention and interpretation (1970), offers
      advice to the reader regarding how he would like his 'early' and 'late' work to
      be read. The author treats the experience of reading these passages as ports of
      entry into the fundamental tenets underlying Bion's widely differing conceptions
      of the psychoanalytic enterprise. The experience of reading early Bion generates
      a sense of psychoanalysis as a never completed process of clarifying obscurities
      and obscuring clarifications, which enterprise moves in the direction of a
      convergence of disparate meanings. In contrast, the experience of reading Bion's
      later work conveys a sense of psychoanalysis as a process involving a movement
      toward infinite expansion of meaning. The author offers a detailed account of an
      analytic experience which he discusses from a point of view informed by Bion's
      work, particularly his late work.

PMID- 15142287
TI  - A risk of confidentiality.
AB  - The concept of confidentiality is examined from its absolute position espoused by
      some psychoanalysts to the many exceptions to this position allowed by others.
      The suggestion made in this paper is offered as a psychoanalytic one which urges
      us to see confidentiality as posing risks in both positions, that is, the
      absolute and the necessary exceptions. Confidentiality is representative of many,
      if not all, of the rules and methods that are implicit in the conduct of an
      analysis and thus may well be taken for granted. The suggestion offered is for a
      periodic re-examination of the implicit background of psychoanalysis.

PMID- 15142288
TI  - The psychodynamic of panic attacks: a useful integration of psychoanalysis and
      neuroscience.
AB  - This article tries to explain, in the light of some neuroscientific and
      psychoanalytical considerations, the repetitive pattern of panic attacks. Freud
      considered the panic attack as an 'actual neurosis' not involving any conflictual
      process. Recent neuroscientific findings indicate that psychosomatic reactions,
      set off by a danger situation, depend on the primitive circuit of fear (including
      the amygdala) characterised by its speed, but lack accurate responses and may
      also be activated by harmless stimuli perceived erroneously as dangerous. The
      traumatic terror is stored in implicit memory and may be set off by a conditioned
      stimulus linked to a previous danger situation. In the panic attack, the
      traumatic event is created by the imagination and this construction (a micro
      delusion), built in loneliness and anxiety, has the same power as the real
      trauma. A mutual psychosomatic short-circuit between body and psyche, in which
      terror reinforces the somatic reactions and the psychic construction, is
      established. Therefore, it is important to highlight these constructions in order
      to analyse and transform them. In the second part of the article the author
      reviews the main psychoanalytical theories about panic attacks, stressing how, in
      his opinion, panic attack is a consequence of the breakdown of the defence
      organisation at various levels and may appear during periods of life crisis. Two
      patients suffering from a deficit of personal identity are presented. The various
      organisations and the different levels (biological, neuroscientific, associative,
      traumatic) of the panic attack determine different kinds of therapeutic
      approaches (pharmacological, cognitive and psychoanalytical). While the
      psychopharmacological treatment is aimed at reducing the neurovegetative reaction
      and the cognitive method is attempting to correct the associative and perceptive
      processes of fear signals, psychoanalytical therapy represents both a specific
      means to free patients from panic attacks as well as an indispensable route for
      their emotional growth.

PMID- 15142290
TI  - The shaping of masculinity: Revisioning boys turning away from their mothers to
      construct male gender identity.
AB  - This paper offers an understanding of the nature of the internalization processes
      involved in the shaping of male gender identity founded on the boy's unique
      struggles in separating from his mother. The underpinning for the initial
      development of a sense of masculinity is reconsidered as the author questions the
      widely held idea of Greenson and Stoller that a boy normatively has to 'dis
      identify' from his mother to create his gender identity. Import rather is placed
      on the conscious and unconscious aspects of the mother's (and father's) pre
      oedipal and oedipal relationship with their little boy in order better to
      understand the nature of the boy's unique identifications and subsequent sense of
      masculinity. Both the security of the boy's attachment to his mother, in
      providing the foundation for a transitional turning to an 'other', and the
      mother's capacity to reflect upon and recognize her own, as well as the father's
      and her son's, subjectivity and maleness, are crucial in comprehending boys'
      'attachment-individuation' process. Likewise, the unconscious paternal and
      maternal imagos and identifications of both the boy's mother and father, as well
      as the father's pre-oedipal relationship with his little boy and the boy's
      mother, are extremely significant in shaping a son's gender identity. The author
      argues that these early maternal (and paternal) identifications live on in every
      male and continue to impact the sense of maleness in a dialectical interplay
      throughout the life span. A maturing gender identity develops from integrating
      these early, pre-oedipal maternal identifications that no longer need be
      repudiated nor defensively organized as polarized gender splitting.

PMID- 15142289
TI  - Intrapsychic-interpsychic.
AB  - The 'interpsychic' is an extended psychic dimension, regarding the joint
      functioning and reciprocal influences of two minds. The concepts of
      'subjectivity' and 'person' can be included in the 'interpsychic'. They can also
      overlap with each other, and sometimes all three can overlap together, but they
      do not necessarily coincide. In the different contemporary perspectives, how can
      we modify the intrapsychic 'through' (and 'with' and 'by') the interpsychic?
      Presenting four clinical vignettes, the author progressively moves from the
      theoretical positions that emphasise the exploration and the elaboration of the
      intrapsychic mainly through the intrapsychic, to the positions that emphasise the
      same operations mainly through the interpsychic. The last part of the paper deals
      with the technical use of the interpsychic dimension: the analytic dialogue, when
      interpsychically experienced (from inside), gains a new, more specific
      effectiveness, first in containing and then in symbolising. In an intense mental
      'cohabitation' inside the analytic working pair, it is very often clearly
      experienced as 'true' (as in dreams).

PMID- 15142291
TI  - The conceptualisation of the psychical in psychoanalysis.
AB  - This article aims to clarify the psychoanalytic conceptualisation of the
      psychical, which includes a discussion of the relationship between consciousness
      and the unconscious. The unconscious is conceived of as being on the border
      between the so-called 'ego's conscious intending' and a rudimentary body-ego
      experiencing. Phenomenological ideas on the essence of consciousness are used in
      order to help delineate the crucial differences between consciousness and the
      unconscious. Only consciousness is characterised by an awareness of itself, that
      is; self-consciousness. Furthermore, consciousness is characterised by an
      intentional, synthesising capacity, whereas the functioning of the unconscious,
      in its most radical form, is the opposite of the intentionality of consciousness.
      It is argued that the unconscious pre-supposes certain pre-sexual processes, in
      the form of a body-ego's formation of continuity, coherence and wholeness. The
      body-ego belongs to the sphere of consciousness/self-consciousness, even if self
      consciousness is only given implicitly in the body-ego and not as a fully fledged
      ego cogito. Attention is drawn to neglected issues in psychoanalytic theorising,
      namely self-consciousness and the constitution of existence. The importance of
      this neglected area for the psychoanalytic process is illustrated with clinical
      examples.

PMID- 15142292
TI  - Envy: one or many?
AB  - This paper reports conceptual and clinical research about envy. It consists of an
      examination and comparison of Klein's points of view of 1952, where the feeling
      of exclusion from the envious object is stressed, and of 1957, based on the split
      death instinct that is projected onto the envied object. These two approaches are
      contrasted with the point of view of the author, where envy is understood as the
      result of a particular kind of object relation, in which the subject registers an
      asymmetry with its peer, that he considers unfair, due to the biased action of an
      idealized omnipotent object, on whom the subject depends and that gives to the
      envied one, and deceives the envious one, leading to experiencing a compound of
      emotions: hatred, love, sense of unfairness, wish of revenge, helplessness and
      incapacity of the subject to provide for himself. The mental state just described
      emerges from clinical observations, and is illustrated with the passage from the
      Bible where Abel, the envied one, is killed by Cain, the envious one, showing
      their relationship with Jehovah, biased in his preferences, a situation
      designated by the author as 'Cain's complex'. In this paper some considerations
      are also made concerning the modalities of envy: penis envy in women, the
      relationship between envy and narcissism, the difference between envy and
      jealousy, and the interpretative handling of envy. To answer the question posed
      in the title, the conclusion is that envy presents a central nucleus with
      different elaborative branches.

PMID- 15142293
TI  - Chaotic possibilities: toward a new model of development.
AB  - Most psychoanalytic models of development and change assume an orderly,
      sequential and predetermined unfolding of psychological functions and structures.
      Interferences with orderly unfolding challenge the individual and may lead to
      pathology. These models derive from a worldview associated with the descriptions
      of change through linear differential equations, which predict a smooth, orderly
      world. The study of complex systems and their associated non-linear dynamics
      predicts a very different kind of world: a world with abrupt changes,
      discontinuities, idiosyncratic developmental lines, and disproportions between
      causes and effects. The worldview of non-linear dynamics suggests new
      possibilities for the psychoanalytic model of change and development, and invites
      confrontation with the adequacy of many widely accepted models. These new
      possibilities include discontinuous, sudden and qualitative shifts not only in
      manifest behavior but also in in-depth psychological functioning.

PMID- 15142294
TI  - What happens in a psychoanalysis? A view through the lens of the analytic process
      scales (APS).
AB  - A group of experienced analysts has developed scales and a coding manual
      illustrated with clinical examples to evaluate recorded analyses and
      psychodynamic therapies. The analytic process scales (APS) assesses three
      dimensions: (1) the contribution of the analyst: helping to develop a
      relationship in which the analyst can provide clarification and interpretation of
      transference and resistance; (2) the contribution of the patient: the
      communication of experience and the expression of feeling in ways which provide
      information about needs, wishes and conflicts, accompanied by self-reflection;
      and (3) interactional characteristics of the emerging relationship, explored by
      studying sessions divided into psychoanalytically coherent segments. A
      preliminary study of nine sessions has established that the variables assessed by
      the APS can be rated reliably. Study of the analysts' contributions illuminated
      their varied and complex structure. Important differences emerged among the three
      patient-analyst pairs studied, and changes in scores over time tracked
      developments in the analytic work which would imply different treatment outcomes.
      The APS appears to be a reliable tool facilitating the systematic study of
      psychoanalyses.

PMID- 15142295
TI  - What can we learn from psychoanalysis and prospective studies about chemically
      dependent patients?
AB  - Despite the common occurrence of drug abusers in the psychoanalytic clinic,
      contemporary literature on the subject, particularly among publications in the
      IJP, is sparse. This paper aims to review the most important psychoanalytic
      contributions on drug dependency in the past 100 years, then attempts to compare
      their postulations to the findings of pertinent prospective studies. In these
      patients, a persistent symbiotic object relationship is found, which ties them to
      narcissistic functioning, where drug use is viewed in the light of both pleasure
      without object and omnipotently controlled need. The author also discusses the
      possible contribution of the mother and father in the genesis of this condition,
      focusing on the compromise of the paternal function as the deciding factor. The
      theoretical and technical implications of this approach are illustrated by
      clinical material.

PMID- 15142296
TI  - Sandor, Gizella, Elma: A biographical journey.
AB  - In recent years, particularly with the publication of the Freud-Ferenczi
      correspondence, it has become clear that the rich theoretical dialogue between
      Freud and Ferenczi, a dialogue that may be seen as constitutive for
      psychoanalytic discourse in recent decades, was intensely intertwined with their
      complex personal relationship. Two women--Gizella Palos, who eventually became
      Ferenczi's wife, and her daughter Elma, who was both Ferenczi's and Freud's
      analysand, and with whom Ferenczi fell in love--played a crucial role in shaping
      the Freud-Ferenczi relationship. Their own voices, however, have so far been
      barely heard. This paper is a preliminary report of a biographical research
      project which aims to complete the puzzle, by getting to know better Gizella,
      Elma and their family, with the help of numerous original sources, many of them
      unpublished till now. The emerging picture tends to confirm Ferenczi's initial
      view of Elma as a person of depth and integrity, rather than Freud's view of her
      as fundamentally disturbed; countertransference-love, it is suggested, may have
      facilitated fuller perception rather than clouding it. The question of the impact
      of Elma's 'confusion of tongues' with Ferenczi and with Freud on her subsequent
      life is also discussed.

PMID- 15142297
TI  - On: Homosexuality: coming out of the confusion.

PMID- 15142298
TI  - Emotion and adherence to treatment in people with asthma: an application of the
      emotional stroop paradigm.
AB  - This study explored whether an emotional Stroop paradigm might represent an
      appropriate means of assessing individuals' emotional representations of asthma.
      In addition, the opportunity was taken to investigate whether emotional
      representations of asthma, as assessed by this method, were associated with
      adherence to inhaled preventative medication. An asthma Stroop task was devised
      which comprised three sets of stimuli: asthma symptom words, general negative
      words, and neutral words. Three groups of participants were compared on their
      performance on this task: individuals with asthma, individuals without asthma,
      and individuals without asthma who had been primed about the condition. It was
      found that individuals with asthma experienced significantly more interference
      when colour-naming the asthma symptom words, but not when colour-naming the
      general negative words. Furthermore, their performance on the asthma Stroop task
      was associated with self-reported adherence levels. Specifically, individuals who
      reported the highest and lowest levels of adherence displayed more interference
      when colour-naming the asthma symptom words than individuals with intermediate
      levels of adherence. It is concluded that the emotional Stroop paradigm might
      provide an objective and sensitive means of assessing individuals' emotional
      representations of illness. Additionally, it is proposed that emotional responses
      to illness should be assessed and included in research designed to explain health
      behaviours and, furthermore, that such research should not assume that any
      relationship between emotional representations and health behaviours will be
      linear.

PMID- 15142300
TI  - A Rasch scaling validation of a 'core' near-death experience.
AB  - For those with true near-death experiences (NDEs), Greyson's (1983, 1990) NDE
      Scale satisfactorily fits the Rasch rating scale model, thus yielding a
      unidimensional measure with interval-level scaling properties. With increasing
      intensity, NDEs reflect peace, joy and harmony, followed by insight and mystical
      or religious experiences, while the most intense NDEs involve an awareness of
      things occurring in a different place or time. The semantics of this variable are
      invariant across True-NDErs' gender, current age, age at time of NDE, and latency
      and intensity of the NDE, thus identifying NDEs as 'core' experiences whose
      meaning is unaffected by external variables, regardless of variations in NDEs'
      intensity. Significant qualitative and quantitative differences were observed
      between True-NDErs and other respondent groups, mostly revolving around the
      differential emphasis on paranormal/mystical/religious experiences vs. standard
      reactions to threat. The findings further suggest that False-Positive respondents
      reinterpret other profound psychological states as NDEs. Accordingly, the Rasch
      validation of the typology proposed by Greyson (1983) also provides new insights
      into previous research, including the possibility of embellishment over time (as
      indicated by the finding of positive, as well as negative, latency effects) and
      the potential roles of religious affiliation and religiosity (as indicated by the
      qualitative differences surrounding paranormal/mystical/religious issues).

PMID- 15142299
TI  - Estimating one's own personality and intelligence scores.
AB  - One hundred and eighty-seven university students completed the full NEO-PI-R
      assessing the five super-traits and 30 primary traits, and the Wonderlic
      Personnel Test of general intelligence. Two months later (before receiving
      feedback on their psychometric scores), they estimated their own scores on these
      variables. Results at the super-factor level indicated that participants could
      significantly predict/estimate their own Neuroticism, Extraversion, and
      Conscientiousness scores. The correlation between estimated and psychometrically
      measured IQ was r=.30, showing that participants could, to some extent,
      accurately estimate their intelligence. In addition, there were a number of
      significant correlations between estimated intelligence and psychometrically
      assessed personality (particularly Neuroticism, Agreeableness and Extraversion).
      Disagreeable people tended to award themselves higher self-estimated intelligence
      scores. Similarly, stable people tended to award themselves higher estimates of
      intelligence (even when other variables were controlled). Regressing both
      estimated and psychometric IQ scores onto estimated and psychometric personality
      scores indicated that the strongest significant effect was the relationship
      between trait scores and self-estimated intelligence.

PMID- 15142302
TI  - First-perspective alignment effects in a computer-simulated environment.
AB  - In Experiment 1, participants explored two desktop, virtual environments (VEs),
      each comprising three city streets connected at right angles; for each
      participant one VE was open and one was enclosed. Following the first VE
      exploration, orientation estimates to remembered test locations were most
      accurate when participants imagined themselves aligned, rather than 90 degrees
      misaligned or 180 degrees or contra-aligned, with the first part of the route. In
      the second VE, the effect was attenuated and the data pattern conformed to that
      anticipated from an orientation-free memory. Experiment 2 followed the procedure
      of Experiment 1, but omitted the alignment tests after the first VE; following
      the second VE exploration, orientation estimates presented a similar pattern to
      those in first test of Experiment 1. These data are discussed in terms of
      cognitive load.

PMID- 15142301
TI  - Trials-to-criterion latent inhibition in humans as a function of stimulus pre
      exposure and positive-schizotypy.
AB  - Latent inhibition (LI) is a phenomenon during which non-reinforced pre-exposure
      to a stimulus retards later learning of associations with that same stimulus. It
      has been suggested that LI is a positive function of the amount of stimulus pre
      exposure (PE) and that with very small amounts of PE, facilitation rather than
      inhibition will occur-particularly in high positive-schizotypes. Although LI has
      been demonstrated as a function of the amount of pre-exposure in animals, human
      findings have not proved to be so uniform or consistent. The primary objective of
      the present study was to establish LI as a function of numbers of pre-exposure on
      visual and auditory trials-to-criterion tasks, with a secondary objective to
      establish latent facilitation (LF) with very low numbers of pre-exposure in high
      positive-schizotypes. Results revealed a uniform pattern of learning across pre
      exposure conditions, including latent facilitation, on the visual, but not the
      auditory task. LF was also observed in the high, but not low, scorers in positive
      schizotypy with very low numbers of pre-exposure on the visual task.

PMID- 15142303
TI  - Measuring cancer knowledge: comparing prompted and unprompted recall.
AB  - Studies evaluating public knowledge of the warning signs and risk factors
      associated with cancer have varied in the question format used. Those using a
      prompted (recognition) format have tended to find higher levels of knowledge than
      those using an unprompted, recall format. The aim of this study was to quantify
      the effect of prompting on knowledge of the seven warning signs of cancer, and
      risk factors for breast and bowel cancer, using data from large representative
      samples of the UK population. We also tested for demographic differences in the
      effect of prompting, hypothesizing that prompting would have the greatest impact
      on groups with least knowledge, specifically men, older and younger people, and
      those with least education. Analysis of data from four ONS surveys (total n =
      5,863) demonstrated significantly higher knowledge of all signs and risk factors
      in the prompted compared with the unprompted condition. Contrary to our
      hypothesis, the pattern of interaction of prompting with gender and level of
      education was inconsistent, and the effect of prompting decreased with increasing
      age. Implications for future research on cancer knowledge and the most
      appropriate question format are discussed.

PMID- 15142304
TI  - Distant intentionality and the feeling of being stared at: two meta-analyses.
AB  - Findings in parapsychology suggest an effect of distant intentionality. Two
      laboratory set-ups explored this topic by measuring the effect of a distant
      intention on psychophysiological variables. The 'Direct Mental Interaction in
      Living Systems' experiment investigates the effect of various intentions on the
      electrodermal activity of a remote subject. The 'Remote Staring' experiment
      examines whether gazing by an observer covaries with the electrodermal activity
      of the person being observed. Two meta-analyses were conducted. A small
      significant effect size (d =.11, p =.001) was found in 36 studies on 'direct
      mental interaction', while a best-evidence-synthesis of 7 studies yielded d =.05
      (p =.50). In 15 remote staring studies a mean effect size of d = 0.13 (p =.01)
      was obtained. It is concluded that there are hints of an effect, but also a
      shortage of independent replications and theoretical concepts.

PMID- 15142305
TI  - A possible model for understanding the personality--intelligence interface.
AB  - Despite the recent increase in the number of studies examining empirical links
      between personality and intelligence (see Hofstee, 2001; Zeidner & Matthews,
      2000), a theoretical integration of ability and nonability traits remains largely
      unaddressed. This paper presents a possible conceptual framework for
      understanding the personality-intelligence interface. In doing so, it
      conceptualizes three different levels of intelligence, namely, intellectual
      ability (which comprises both Gf and Gc), IQ test performance and subjectively
      assessed intelligence (a mediator between personality, intellectual ability and
      IQ test performance). Although the model draws heavily upon correlation evidence,
      each of its paths may be tested independently. The presented model may,
      therefore, be used to explore causation and further develop theoretical
      approaches to understanding the relation between ability and nonability traits
      underlying human performance.

PMID- 15142306
TI  - A look at malingering.

PMID- 15142307
TI  - Examining the use of the M-FAST with criminal defendants incompetent to stand
      trial.
AB  - The Miller Forensic Assessment of Symptoms Test (M-FAST) was developed to provide
      evaluators with a brief, reliable, and valid screen for malingered mental
      illness. This study examined the initial validity of the M-FAST in a sample of 50
      criminal defendants found incompetent to stand trial because of a mental illness.
      The M-FAST total score and items were compared with the Structured Interview of
      Reported Symptoms (SIRS) and the fake-bad indicators of the Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2). Results indicated good evidence of construct
      and criterion validity, demonstrated by t tests, receiver operating
      characteristics analysis, and high correlations between the M-FAST, SIRS, and the
      fake-bad indices on the MMPI-2. Tentative cut scores for the M-FAST total score
      and scales were examined and demonstrated high utility with the sample of
      criminal defendants incompetent to stand trial.

PMID- 15142308
TI  - Life strain, negative emotions, and delinquency: An empirical test of general
      strain theory in the People's Republic of China.
AB  - Using a sample of 615 middle school and high school students from both rural and
      urban areas of the People's Republic of China, this study tests the central
      hypotheses concerning the mediating model in Agnew's general strain theory. The
      analyses focus on the intervening mechanisms of negative emotions such as anger,
      resentment, anxiety, and depression that connect exposure to interpersonal strain
      with delinquent outcomes, including both serious delinquency and minor offenses.
      The results show that anger mediates the effect of interpersonal strain on
      violence, resentment mediates the effect of interpersonal strain on nonviolent
      delinquency, and anxiety and depression have a mediating effect on the
      relationships between interpersonal strain and minor offenses. The findings are
      generally consistent with the results of earlier studies in the United States.

PMID- 15142309
TI  - Parental efficacy, self-control, and delinquency: A test of a general theory of
      crime on a nationally representative sample of youth.
AB  - Criminologists have recently begun examining Gottfredson and Hirschi's (1990)
      proposition that parenting is the primary influence on children's levels of self
      control. The few existing studies on the subject, however, have typically been
      based on small, nonrandom samples. The current study examines the relationships
      between parental efficacy, self-control, and delinquent behavior using data from
      a nationally representative sample of adolescents (the National Longitudinal
      Study of Adolescent Health). The results indicate that although parental efficacy
      is an important precursor to self-control, contrary to Gottfredson and Hirschi's
      proposition, self-control does not completely mediate the relationship between
      parental efficacy and delinquency. The implications for future research and
      theoretical development are discussed.

PMID- 15142310
TI  - Believing is seeing II: Beliefs and perceptions of criminal psychological
      profiles.
AB  - This study built upon previous research by Kocsis and Hayes (2004) by
      investigating whether a bias exhibited by police officers in their perception of
      profiles would replicate in a sample of nonpolice participants. Additionally, the
      relationship, if any, between the degree of belief harbored by an individual
      concerning the merits of profiling and their perceptions of a given profile was
      also investigated. The findings of this study add to the contention that the
      biases observed in Kocsis and Hayes's previous study with regard to author label
      may be related to some intrinsic feature of the previously sampled police
      participants. Additionally, evidence was found to support the proposition that an
      individual's degree of belief in profiling is related to their perceptions
      concerning the merits of a profile. Namely, the more an individual believes in
      the profiling technique, the greater the merit that will be perceived in a
      profile.

PMID- 15142311
TI  - Criminal justice institutional referrals and selections: a comparative portrait
      of sexual aggressions and aggressors.
AB  - The purpose of this study is to investigate the judicial treatment of sex
      offenders from police detection to treatment centers. Using three different
      samples, participants' trajectories are studied in the light of their age, the
      age and sex of their victims, the relationship with their victims, and the use of
      a weapon. First, the results show that although underrepresented at the federal
      institution, younger criminals tend to be overrepresented in the treatment
      sample. Second, the results also demonstrate that offenders against children tend
      to be overrepresented at the federal institution; this tendency is even stronger
      in the psychiatric treatment sample. Third, the objective seriousness of the
      offense, a proxy measured by the presence of a weapon, is of principal importance
      in case processing throughout the judicial system. Recommendations on how to
      facilitate the comparison of results from different studies, based on a better
      sample description, are also discussed.

PMID- 15142312
TI  - The recruitment and retention of indigenous criminal justice agency staff in an
      Australian state.
AB  - In Australia, as in other countries that have experienced colonisation,
      indigenous people are massively overrepresented in all stages of the criminal
      justice system. If criminal justice agencies are to provide culturally responsive
      and effective services to this group, it is important that they employ
      significant numbers of indigenous staff across all levels of their organisations.
      Despite the positive intentions of many justice agencies to increase the
      proportion of indigenous staff members they employ, the numbers remain low. In
      this article, we explore some of the possible reasons for this by reporting the
      results of focus groups conducted with existing indigenous justice agency
      employees. The employees raised a number of issues relevant to recruitment and
      retention. These are discussed in terms of their potential value in improving
      justice agency indigenous recruitment and retention strategies.

PMID- 15142313
TI  - The generalized instructional set of the Criminal Attribution Inventory (CRAI):
      socially desirable responding and faking.
AB  - Accurate assessment of criminal attributions can assist in explaining crime and
      identifying offender treatment targets. The current study examines the
      relationship between a new method of assessing the cognition of criminal
      attributes, the Criminal Attribution Inventory (CRAI) and a measure of socially
      desirable responding. 300 participants including incarcerated offenders, released
      offenders, sex offenders, and university students participated in the current
      study. Results indicate minimal relationships between socially desirable
      responding and the CRAI. In a fake-good testing situation, the faking index had
      appropriate sensitivity, specificity, and positive and negative predictive power
      in identifying fake-good responses. The CRAI's instructional set of general
      observation as opposed to self-representation appears to limit socially desirable
      responding and also allows the CRAI to be administered to nonoffender
      populations.

PMID- 15142314
TI  - Community Service Orders in Hong Kong, England, and Wales: twins or cousins.
AB  - Hong Kong's Community Service Order (CSO) is anchored in the probation service
      and has not had to face problems related to the cultural divide and professional
      rivalry between community service and probation staff similar to England and
      Wales. CSOs in both jurisdictions differ in offenders' minimum age and in seeking
      offenders' consent and have been rarely used for young offenders. They have
      widened the net of social control, and there have been difficulties in
      positioning them in the sentencing tariff. Although retributive penal practices
      might have crept into Hong Kong after China's takeover in 1997, its CSO has
      retained rehabilitative elements. In England and Wales, the renaming of CSO as
      the Community Punishment Order reaffirmed its retributive nature, however the
      Pathfinder projects have taken it back to its origins as a rehabilitative
      measure. We suggest that CSOs should move further toward restorative justice by
      the involvement of victims in the choice of community services.

PMID- 15142315
TI  - Multisystemic therapy for antisocial juveniles: suggestions for improvement.

PMID- 15142316
TI  - Transplantation immunology and the central nervous system.
AB  - Controlled clinical trials of cell transplantation for Parkinson's disease
      yielded disappointing results. Significant long-term functional improvement was
      not observed and cell survival was low. Although the brain was traditionally
      considered as "immunologically privileged" recent findings demonstrated late
      increase in the number of microglia around the grafts, therefore implying an
      involvement of immune mechanisms. The immunology of organ and cell
      transplantation to other body locations is scrupulously investigated and
      significant stepping-stones have been achieved. Ample evidence regarding the role
      of antigen-presenting cells in graft rejection has been documented. However, this
      knowledge did not benefit the discipline of cell transplantation to the central
      nervous system, and the minimal consideration of potential immune responses
      remain empirical in nature. In this review we summarize current knowledge of the
      major histo-compatibility complex and its role in transplant immunology. Resident
      cells of the brain that take part in immune responses are also discussed. Based
      on this information we hypothesize that the immune mechanisms involved with the
      long-term graft failure of cell transplantation to the central nervous system are
      likely to be chronic, and not acute, rejection. This, in turn, should have
      significant importance in the choice of anti-rejection drugs to be used.

PMID- 15142317
TI  - Transplantation for stroke.
AB  - Stroke is the most common cause of disability in the United States, and one of
      the leading causes of mortality and disability in the world. The hope that damage
      to the CNS can be reversed or at least ameliorated is the central idea behind the
      research into neural repair. The ultimate repair for the brain should restore the
      entire lost structure and it's function. However, partial benefit is possible
      from addressing some of the needs of the injured brain. These partial solutions
      are the basis of current research into brain repair after stroke. An opportunity
      arises for two kinds of intervention: (1) replacement of neurons; (2) support of
      existing neurons, to prevent excessive degeneration and promote rewiring and
      plasticity. Transplantation for stroke in the rat model was regularly reported
      starting in 1992, demonstrating graft survival and even evidence of connection
      with the host brain. These studies determined several parameters for future work
      in stroke models, but ultimately had limited efficacy and did not progress to
      clinical experiments. A variety of cell types have been tried for restoration of
      brain function after stroke, mostly in rodent models. Human fetal cells had shown
      some promise in clinical studies for the treatment of Parkinson's disease. The
      technical and ethical difficulties associated with these cells promoted a search
      for alternatives. These include porcine fetal cells, human cultured stem cells,
      immortalized cell lines, marrow stromal cells, Sertoli cells pineal cells, and
      other sources. Human clonal cell lines have few ethical limitations, but some
      questions remain regarding their safety and efficacy. Autologous somatic stem
      cells are a very attractive source--there are no ethical concerns and graft
      rejection is not an issue. However, it is not clear that somatic cells can are
      plastic enough and can be safely induced to a neural fate. Restorative treatment
      for stroke is a new field of study. Naturally, new ideas abound and many
      strategies have been suggested and tried. Methods and controversies abound, and
      include: local delivery of cells to the area of the stroke versus grafting to an
      area of the brain far removed form the stroke; cell therapy for reconstitution of
      structure and function versus use of cell grafts to support intrinsic repair and
      recovery mechanisms; intravascular administration of bone marrow or other stem
      cells; and combination grafts, or co-grafting of several cell types or cells and
      other substances. The various strategies address the issue of restorative
      treatments form different perspectives. Some interventions occur early after
      stroke, or are intended to preserve existing neural structures. For example,
      treatment strategies that aim to provide trophic support may demonstrate early
      beneficial results. Other strategies aim for growth and integration of new
      neurons to replace those lost after stroke. In this case, early beneficial
      results are not likely. Functional integration of grafted neurons, if it can ever
      happen, is likely to require training and exercise of the appropriate capacities.
      Further advances in preclinical studies of neural transplantation will require
      improved animal models with increased sensitivity to subtle behavioral and
      imaging changes. Non-human primate models have been established and may increase
      in importance as a phase before clinical trials. The future of brain repair for
      stroke is likely to require some form of combination therapy designed to replace
      the lost cells and supporting structure, attract new blood supply, support and
      enhance intrinsic repair and plasticity mechanisms.

PMID- 15142319
TI  - Neomycin inhibits glioma cell migration.
AB  - Blocking migration is an attractive strategy to inhibit glioma tumorigenesis.
      Previous studies have indicated that neomycin inhibits glioma cells
      proliferation. The purpose of this study was to expand on the preliminary
      research by investigating the antimigratory effect of neomycin. We used glioma C6
      cells to investigate the role of neomycin in cell migration in vitro. Cell
      wounding assay showed that neomycin inhibits in a dose-dependent manner glioma
      cells migration into the wound. Taken together, these results suggest that
      neomycin is an attractive candidate for the development of novel antimigratory
      molecules useful for the treatment of gliomas.

PMID- 15142318
TI  - Intraventricular transplantation of embryonic stem cell-derived neural stem cells
      in intracerebral hemorrhage rats.
AB  - In the present study, we attempted to explore cell transplantation therapy for
      intracerebral hemorrhage (ICH) using embryonic stem (ES) cells. Collagenase
      induced ICH rats were used as model animals. Mouse ES cells were differentiated
      into nestin-positive neural stem cells in vitro by alltrans retinoic acid (ATRA).
      ATRA-treated ES cells (10(5)) were transplanted into the lateral ventricle in the
      hemisphere contralateral to the hemorrhage 7 days after collagenase infusion.
      Twenty-eight days after transplantation, ES-derived neurons and astrocytes were
      observed around the hematoma cavities of the brain in all of the ten rats
      receiving grafts. Graft-derived neurons were found in the subependymal area of
      the lateral ventricle as cellular nodules. Although one of the ten rats receiving
      grafts showed uncontrolled growth of astroglia derived from the ES cells,
      intraventricular transplantation of ATRA-treated ES cells is an effective
      delivery system of neuronal lineage-committed progenitor cells toward the site of
      ICH.

PMID- 15142320
TI  - Basilar artery to bilateral posterior cerebral artery 'Y stenting' for
      endovascular reconstruction of wide-necked basilar apex aneurysms: report of
      three cases.
AB  - Endovascular reconstruction of basilar artery (BA) apex aneurysms has been
      augmented by adjunctive techniques such as balloon and stent assistance. We
      present three cases of a wide-necked BA apex aneurysm involving the bilateral P1
      segments of both posterior cerebral arteries (PCAs) treated by placement of BA to
      PCA stents bilaterally in a 'Y' configuration to reconstruct the BA apex for
      effective coil embolization. Three patients (aged 70, 65 and 37 years) with wide
      necked basilar artery aneurysms presented for endovascular treatment. All
      aneurysms had necks that involved the bilateral P1 segments. Each patient was
      deemed an appropriate candidate for endovascular reconstruction. Patients were
      pretreated with clopidogrel (75 mg) and aspirin (325 mg) each day for 3 days
      prior to the procedure. Following induction of general anesthesia, access to the
      right femoral artery was obtained by placement of a 6F sheath. Intravenous
      heparin was administered to achieve an activated coagulation time (ACT) of
      approximately 300 seconds. A 6F guide catheter was placed within the left
      vertebral artery (VA) in two patients, the right VA in a third. Utilizing over
      the-wire (OTW) technique, a microcatheter was advanced into the left P2-P3
      junction of the PCA. A 300-cm 0.014-inch microwire was passed through the
      microcatheter into the distal PCA and the microcatheter was removed. In each
      case, two neuroform stents were prepared (SMART Therapeutics Inc., San Leandro,
      CA) and advanced OTW into the PCA with the most acute angle relative to the BA.
      The initial stent placed was 20 mm in length and was deployed from the P1 segment
      into the BA. The microwire was pulled retrograde into the BA apex, then advanced
      though the stent struts and into the right PCA. A second stent, 15 mm in length,
      was advanced OTW through the struts of the previously placed stent. It was then
      deployed from the P1 into the BA where it overlapped the first stent, resulting
      in a stent-in-stent 'Y' configuration at the BA apex. A microcatheter was
      advanced OTW into the BA apex aneurysm and coil embolization proceeded in the
      usual fashion. Following the procedure, each patient was maintained in the
      neurosurgical intensive care unit (NICU). All remained neurologically intact. The
      two elderly patients were discharged to home the morning following the procedure.
      The third patient suffered an upper GI bleed and was treated an additional 3 days
      in hospital. Oral clopidogrel (75 mg by mouth) and aspirin (325 mg by mouth) were
      continued daily for 4 weeks. The 'Y' stent configuration for reconstruction of
      the BA apex is a safe effective technique in patients with wide-necked BA
      aneurysms.

PMID- 15142321
TI  - Motor imagery task classification for brain computer interface applications using
      spatiotemporal principle component analysis.
AB  - Classification of single-trial imagined left- and right-hand movements recorded
      through scalp EEG are explored in this study. Classical event-related
      desynchronization/synchronization (ERD/ERS) calculation approach was utilized to
      extract ERD features from the raw scalp EEG signal. Principle Component Analysis
      (PCA) was used for feature extraction and applied on spatial, as well as temporal
      dimensions in two consecutive steps. A Support Vector Machine (SVM) classifier
      using a linear decision function was used to classify each trial as either left
      or right. The present approach has yielded good classification results and
      promises to have potential for further refinement for increased accuracy as well
      as application in online brain computer interface (BCI).

PMID- 15142322
TI  - Concept of arteriovenous malformation compartments and surgical management.
AB  - Cerebral AVMs are known to be a source of intracranial hemorrhages and epileptic
      seizures. Their natural history indicates approximately 15% mortality and 35%
      morbidity over a 15-year period. This significant mortality and morbidity
      mandates a need for satisfactory treatment of this entity, ideally by elimination
      of AVMs. Microsurgical resection, endovascular embolization and radiosurgery
      (irradiation) are the three effective modes of treatment currently available.
      However, no objective criteria have been established for which mode(s) of
      treatment should be selected for individual patients with AVMs. Considering the
      complexity of AVMs and variable conditions of individual patients, neurosurgeons,
      intravascular interventionalists and radiosurgeons must make their own decisions
      on how to treat each patient based on their experience. In practice, treatment of
      small AVMs in non-functional areas is favored equally by each of these
      specialists, while they tend to avoid treatment of large AVMs, particularly those
      in functional areas of the brain. The authors report the surgical intervention of
      large AVMs, including those located in functional areas of the hemisphere by
      special techniques. One can demonstrate AVM compartments by using angiography and
      with the aid of color Doppler ultrasonography, each compartment can be outlined
      and dissected individually until all the compartments are isolated without
      causing any damage to the surrounding brain and the entire AVM is rendered
      shrunken and then removed. The concept of compartmental treatment of AVMs may be
      applied in the future to radiosurgery and intravascular embolization of large
      AVMs.

PMID- 15142324
TI  - Aging enhances vascular dysfunction induced by the Alzheimer's peptide beta
      amyloid.
AB  - Aging is a major risk factor for Alzheimer's disease and the evidence suggests a
      role for cerebrovascular pathology in cognitive dysfunction. The hypothesis in
      this study is that aging is a significant risk factor in the effect of the
      Alzheimer peptide beta-amyloid on endothelium-dependent function of cerebral and
      peripheral vessels. The diameter response to acetylcholine, an endothelium
      dependent vasodilator, was recorded in pressurized segments of rat posterior
      cerebral vessels from mature (3 months) and aged (20 months) rats. The threshold
      concentration of beta-amyloid for a significant decrease in the response to
      acetylcholine was lower in vessels from aged rats (10(-9) M) than in vessels from
      mature rats (10(-8) M). The threshold concentration of beta-amyloid for a
      significant decrease in the sensitivity to acetylcholine was lower for ring
      segments of aorta from aged rats (10(-10) M) than for aorta from mature rats (10(
      8) M). Structural changes of the endothelium were first observed in electron
      micrographs of aorta from aged rats when the concentration of beta-amyloid was
      10(-8) M, whereas structural changes in aorta from mature rats did not occur
      until the concentration of beta-amyloid was increased to 10(-7) M. The results
      suggest that aging increases the susceptibility of cerebral and peripheral blood
      vessels to beta-amyloid related dysfunction and that functional change precedes
      structural change.

PMID- 15142325
TI  - Fluctuations in vancomycin CNS tissue concentrations following intermittent and
      continuous infusions in the rat.
AB  - The purpose of this investigation was to compare the variability of vancomycin
      concentrations in the serum and CNS when administered continuously or as
      intermittent intravenous infusions in the rat. The hypothesis for this
      investigation was that the magnitude of change in serum vancomycin concentrations
      directly relates to the extent of vancomycin concentration fluctuations in the
      CNS. Microdialysis and serum sampling techniques were employed and biologic
      samples were analysed for vancomycin using HPLC. Over the dosing interval, the
      mean changes in concentrations were 71.8 +/- 9.8% and 13.6 +/- 9.3% for serum and
      61.7 +/- 7.8% and 6.8 +/- 3.5% for brain extracellular fluid in the intermittent
      and continuously infused groups, respectively. Accordingly, the relative changes
      in vancomycin concentrations in brain extracellular fluid were closely associated
      with corresponding changes in serum concentrations (R2=0.94). Thus, continuous
      intravenous administration of vancomycin results in minimal serum and CNS tissue
      concentration changes as compared to traditional intermittent dosing methods and
      allows for more consistent vancomycin concentrations in the CNS.

PMID- 15142323
TI  - Pseudo-aneurysms associated with intracranial surgery: case report.
AB  - We describe a patient in whom two non-symptomatic internal carotid artery and
      middle cerebral artery pseudo-aneurysms were diagnosed 1 year following the
      surgical removal of a clinoidal meningioma. The unusual number, location, form
      and evolution (actual follow up of 6 years) of these pseudo-aneurysms
      differentiate them from other vascular lesions associated with surgery. It is
      important to understand the mechanism of vascular injury in order to understand
      imaging features and the possible methods of treatment.

PMID- 15142326
TI  - Mental Status Expert: an expert system for scoring and reporting the mental
      status examination.
AB  - For neurology clerks and residents, the mental status examination is often the
      most difficult part of the neurological examination. We have developed the Mental
      Status Expert (MSE), a structured mental status examination designed for use by
      neurology student clerks and neurology residents. The MSE assesses seven areas of
      cognitive function: orientation and concentration, language, right parietal
      functions, left parietal functions, occipital lobe functions, frontal lobe
      functions, and memory. Norms for the test have been created based on
      administration to 281 subjects referred to the Neurology Clinic. The MSE uses
      production rules and other expert system features to assist in the scoring and
      reporting of test results.

PMID- 15142327
TI  - Efficacy of vertebral axial decompression on chronic low back pain: study of
      dosage regimen.
AB  - Vertebral axial decompression (VAX-D) is capable of reducing intradiscal pressure
      to the negative range. The purpose of this study was to compare the effects of
      two dosage regimens of VAX-D treatments on the level of low back pain in patients
      who were referred to a neurosurgical practice after failing standard medical
      therapy. In this study, one group of patients received an average course of
      treatment consisting of 18 daily sessions and another group received half that
      number of daily treatment sessions. The treatment parameters for all patients
      differed only in the number of sessions. Seventy-six percent of the higher dosage
      group achieved remission of low back pain compared to 43% of the lower dosage
      group. Chi-squared analysis revealed that the differences in response in the two
      dosage groups were statistically significant at p< 0.0001.

PMID- 15142328
TI  - The identification of right-to-left shunts using contrast transcranial Doppler
      ultrasound: performance and interpretation modalities, and absence of a
      significant side difference of cardiac micro-emboli.
AB  - Cardiac and extracardiac right-to-left shunts can be identified by
      transesophageal echocardiography (TEE) as well as by transcranial Doppler
      ultrasound (TCD) using contrast agents that do not pass the lungs. Currently, the
      appropriate performance of a Valsalva manoeuvre (VM) to provoke the shunt, the
      use of different contrast agents and the classification of the TCD results are
      still under debate. In this study, we looked also at possible side effects of
      provoked cardiac micro-emboli in the left and right hemisphere. Seventy-one
      patients were investigated by both TEE and bilateral TCD of the middle cerebral
      arteries. The following protocol was applied in a randomized way: (1) Echovist
      300 without VM; (2) Echovist-300, VM for 5 seconds starting 5 seconds after the
      beginning of contrast injection; (3) repetitive short VMs in between 2 and 13
      seconds after the beginning of Echovist-300 injection; and (4) repetitive short
      VMs in between 2 and 13 seconds after the beginning of agitated saline injection.
      Only if one of the tests (2-4) was negative, this particular negative test was
      repeated. Use of Echovist-300, but not of saline yielded 100% sensitivity in the
      detection of TEE-proven shunts. The repetitive VM was slightly superior to the
      conventional VM. Introduction of a threshold of two or even three microbubbles
      produced less falsely positive TCD results in comparison to the TEE. There was no
      difference in microbubbles. TCD using Echovist-300 is a sensitive method to
      identify TEE-proven cardiac right-to-left shunts. Repetitive VM is an alternative
      to conventional VM.

PMID- 15142330
TI  - Direct percutaneous carotid artery stenting with distal protection: technical
      case report.
AB  - We describe the technique of percutaneous carotid artery stent placement with
      distal protection in a patient in whom marked innominate artery ectasia prevented
      transfemoral access to the right common carotid artery. After induction of
      general anesthesia, ultrasound was used to guide direct puncture of the common
      carotid artery followed by the introduction of a 5 French sheath. A GuardWire
      distal protection balloon (Medtronic, Santa Rosa, CA) was placed distal to the
      lesion and deployed at nominal diameter. A balloon-expandable stent was deployed
      without difficulty. Following stent placement, angiography demonstrated improved
      flow in the entire right carotid artery territory. There were no complications
      related to cervical soft tissue damage or clinical embolism. The patient
      tolerated the procedure well and was discharged in 24 hours. Direct carotid
      access is acceptable in select patients in whom a transfemoral, brachial, or
      transradial approach is technically difficult. The use of distal cerebral
      protection devices may reduce cerebral embolism associated with these procedures.

PMID- 15142329
TI  - Handedness and macular vision: laterality of motor control underpins both.
AB  - This article pursues the corollaries of the anatomy of handedness recently
      discovered. Specifically, it addresses the issues concerning central vision as it
      relates to the command center and the circuitry of the saccades. It presents data
      that support the directionality of callosal traffic in motor and sensory realms
      even further. Evidence is presented that denotes a relationship between the
      anatomy sustaining movement control and that responsible for the part of the
      vision handled by the maculae. The evidence shows bypassing of the callosum by
      fibers serving the central vision. This aspect has ramifications for surgical
      approach to the third ventricle by callosotomy, relaxing the earlier prohibitions
      advocated in approaching the third ventricle via splenectomy.

PMID- 15142332
TI  - Ca(2+), calpain and 3-phosphorylated phosphatidyl inositides; decision-making
      signals in neutrophils as potential targets for therapeutics.
AB  - The chemical signals within neutrophils that control their behaviour are complex
      and these signals control the complex activity of neutrophils with precision.
      Failure of neutrophils to reform their antibacterial activity would lead to
      infection, while over-activity of neutrophils may lead to tissue damage and
      inflammatory disease. The identity of some of the intracellular signals is
      becoming clear and insights into the potential for interplay between them are
      being sought. Although it is well established that cytosolic free Ca(2+) plays a
      role, it is only recently that the importance of intracellular protease, calpain,
      and the 3-position phosphorylated phosphatidyl inositides is becoming recognised.
      In this review these three key signals are discussed as potential therapeutic
      targets for the modulation of neutrophil activity.

PMID- 15142331
TI  - Extension of ischemic therapeutic time window by a free radical scavenger,
      Edaravone, reperfused with tPA in rat brain.
AB  - 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) is a free radical scavenger. We
      tested the hypothesis that combination treatment of Edaravone and recombinant
      tissue plasminogen activator (tPA) extends the therapeutic time window. Male
      Wistar rats were subjected to 1.5-, 3.0- or 4.5-hour middle cerebral artery (MCA)
      occlusion (MCAO) by a nylon thread. Animals were randomly divided into four
      groups. The Sham group rats were operated without MCAO and drug injection. In the
      Vehicle-treated group the same volume of saline was given every 1.5 hours from
      just after MCAO to just before reperfusion. In the Vehicle + tPA-treated group
      saline injection was given as above and tPA (5 mg/kg, i.v.) was given once just
      after reperfusion. Edaravone+tPA-treated group: Edaravone (3 mg/kg, i.v.) was
      given every 1.5 hours instead of saline and tPA injection as above. Survival
      rate, infarct size and evidence of apoptosis and hemorrhage were examined in the
      animals. Combining administration of Edaravone+tPA significantly increased
      survival rate after 3 hours of transient MCAO, and reduced infarct volume after
      1.5 hours of transient MCAO compared with the vehicle or vehicle+tPA groups. In
      Edaravone+tPA-treated group, the number of terminal deoxynucleotidyl transferase
      mediated dUTP-biotin in situ nick end labeling (TUNEL) and 4-hydroxynonenal (4
      HNE) positive cells were reduced at 16 hours after 3 hours of transient MCAO, but
      not in advanced glycation end products (AGEs) and 8-hydroxy-2'-deoxyguanosine (8
      OHdG). Hemorrhage rate and the area decreased in the Edaravone+tPA-treated group.
      The combination therapy of Edaravone+tPA increased survival rate, and reduced the
      infarct volume and hemorrhage with reduction of lipid peroxidation. Therefore,
      Edaravone combination is expected to extend the therapeutic time window of tPA in
      the clinical situation.

PMID- 15142333
TI  - A comparison of pseudo-ternary diagrams of aqueous mixtures of Quil A,
      cholesterol and phospholipid prepared by lipid-film hydration and dialysis.
AB  - Pseudo-ternary diagrams for Quil A, phospholipid (phosphatidylcholine (PC) or
      phosphatidylethanolamine (PE)) and cholesterol were established in order to
      identify combinations that result in the formation of immune-stimulating complex
      (ISCOM) matrices and other colloidal structures produced by these three
      components in aqueous systems following lipid-film hydration or dialysis (methods
      that can be used to produce ISCOMs). In addition, the effect of equilibration
      time (1 month at 4 degrees C) on the structures formed by the various
      combinations of the three components was investigated. Depending on the ratio of
      Quil A, cholesterol and phospholipid, different colloidal particles, including
      ISCOM matrices, liposomes and ring-like micelles, were found irrespective of the
      preparation method used. In contrast, worm-like micelles were only observed in
      systems prepared by lipid-film hydration. For samples prepared by dialysis, ISCOM
      matrices were predominantly found near the Quil A apex of the pseudo-ternary
      diagram (> 50% Quil A). On the other hand, for samples prepared by lipid-film
      hydration, ISCOM matrices were predominantly found near the phospholipid apex of
      the pseudo-ternary diagram (> 50% phospholipid). The regions in the pseudo
      ternary diagrams in which ISCOM matrices were observed increased following an
      extended equilibration time, particularly for samples prepared by lipid-film
      hydration. Differences were also observed between pseudoternary diagrams prepared
      using either PE or PC as phospholipids.

PMID- 15142334
TI  - Bupivacaine hydrochloride complexation with some alpha- and beta-cyclodextrins
      studied by potentiometry with membrane electrodes.
AB  - Membrane electrodes selective to bupivacaine cations were developed and those
      with PVC-dibutylphthalate membrane containing sparingly soluble bupivacaine
      phosphotungstate appeared to be the most suitable. Inclusion complexation of
      bupivacaine cations with cyclodextrins was studied by potentiometric measurements
      of the free bupivacaine cation concentration in aqueous solutions of bupivacaine
      hydrochloride with cyclodextrin using the prepared electrodes. Native alpha
      cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD), as well as their random
      substituted derivatives hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD),
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and methyl-beta-cyclodextrin (M-beta
      CD), were chosen for the study. The measured potentiometric data processed both
      by a linear and nonlinear regression corroborated the formation of weak 1:1
      bupivacaine cation-cyclodextrin complexes and the corresponding complexation
      constants K(11) approximately 50-155 M(-1) were evaluated by the non-linear least
      squares method. The mutual order of K(11) values, especially alpha-CD > beta-CD,
      suggested that the bupivacaine butyl group was mainly responsible for the
      inclusion complexation; the highest K(11) was exhibited by M-beta-CD followed by
      alpha-CD. The observed complexation may substantially modify properties of
      bupivacaine hydrochloride dosage forms with sufficient concentration of
      cyclodextrin but bupivacaine cations are readily released from the weak
      cyclodextrin complexes by dilution.

PMID- 15142335
TI  - Pharmaceutical evaluation of liquorice before and after roasting in mice.
AB  - Liquorice has been used for allergic-inflammatory and liver disorders in both
      traditional Chinese and modern medicine. In traditional Chinese formulations, it
      is mainly roasted liquorice that has been used rather than un-roasted liquorice.
      We have compared the pharmaceutical characteristics of liquorice before and after
      roasting to clarify the pharmaceutical significance of the roasting. Although
      roasted liquorice contained less glycyrrhizin (an anti-allergic component) than
      un-roasted liquorice, the inhibitory potency of roasted liquorice extract (200 mg
      x kg(-1)) on immunoglobulin E (IgE)-mediated triphasic ear swelling in mice was
      much greater compared with un-roasted liquorice. To search for additional active
      ingredients, roasted liquorice extract was subjected to gel-chromatography to
      give an anti-allergic fraction (Fa) of molecular weight ranging from 15000 to
      200000 or more, in which glycyrrhizin was not detected. By testing the activity
      of the various fractions, it was proved that the anti-allergic effect of roasted
      liquorice was due to glycyrrhizin, its metabolite glycyrrhetic acid, and the Fa
      fraction. The inhibitory potency of the Fa fraction (15 and 75 mg x kg(-1))
      prepared from roasted liquorice was stronger than that prepared from un-roasted
      liquorice. Therefore, a pharmaceutical implication of roasting the liquorice
      seems to be associated with an increase in the anti-allergic property of the Fa
      fraction. It is notable that oral administration of the high molecular mass
      fraction (Fa) significantly inhibited IgE-mediated ear swelling six days after
      challenge at doses as low as 3, 15 or 75 mg x kg(-1).

PMID- 15142336
TI  - Biodegradable microspheres for prolidase delivery to human cultured fibroblasts.
AB  - Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by
      inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for
      which there is not, as yet, a resolutive cure. We have investigated whether
      biodegradable microspheres loaded with prolidase could release active enzyme
      inside cells, to consider this system as a possible therapeutic approach for
      prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared,
      modifying the classical double emulsion solvent evaporation method to mitigate
      the burst effect of the enzyme from the microspheres. Ex-vivo experiments were
      performed, by incubating microencapsulated prolidase with cultured fibroblasts
      from PD patients and from controls, to determine the amount of active enzyme
      delivered to the cells. The microparticulate drug delivery system described
      carried small amounts of active prolidase inside fibroblasts, ensuring a response
      to the intracellular accumulation of X-Pro dipeptides, the mechanism that is
      supposed to be responsible for the development of clinical manifestations of this
      disorder in man. A positive result of the presence of active enzyme inside cells
      was an improvement in fibroblast shape.

PMID- 15142337
TI  - Media to simulate the postprandial stomach I. Matching the physicochemical
      characteristics of standard breakfasts.
AB  - To better predict food effects on the bioavailability/bioequivalence of drugs and
      drug products from in-vitro data, a dissolution medium that simulates the initial
      composition of the postprandial stomach was developed. First, the physical
      parameters of two homogenized standard breakfasts often administered to assess
      food effects in pharmacokinetic studies were measured. These included pH, buffer
      capacity, osmolality, surface tension and viscosity. Subsequently, the match of
      the physical parameters of several commercially available liquid meals, including
      long-life milk, Ensure and Ensure Plus to those of the breakfasts was evaluated.
      Of the three liquid meals studied, Ensure Plus had the closest physicochemical
      behaviour to that of homogenized standard breakfasts. By increasing the viscosity
      of Ensure Plus with 0.45% pectin, it was possible to obtain a medium that closely
      resembles the FDA standard breakfast.

PMID- 15142338
TI  - On the stability of insulin delivered through a new glucose-responsive polymeric
      composite membrane.
AB  - A new glucose-responsive polymeric composite membrane that provided pulsatile
      insulin release was developed in our laboratory previously. To develop a
      clinically useful insulin delivery system, this study was designed to investigate
      factors influencing insulin stability during delivery by this membrane. The
      effects of stirring, release duration, insulin concentration and surfactant on
      insulin stability were studied under both incubation and delivery conditions in a
      buffer solution at 37 degrees C. The structural change of insulin was
      characterized by reverse-phase HPLC and circular dichroism. Hydrophobicity of
      various contact surfaces was determined by contact angle measurement. The results
      indicated that insulin concentration played an important role in the insulin
      stability, followed by stirring. Treating the membrane with a non-ionic
      surfactant prevented insulin denaturation during delivery through the membrane.

PMID- 15142339
TI  - In-vitro permeation of the insect repellent N,N-diethyl-m-toluamide (DEET) and
      the sunscreen oxybenzone.
AB  - The permeation behaviours of the insect repellent N,N-diethyl-m-toluamide (DEET)
      and the sunscreen oxybenzone were assessed in a series of in-vitro diffusion
      studies, using piglet skin and poly (dimethylsiloxane) (PDMS) membrane. The
      transmembrane permeability of DEET and oxybenzone across piglet skin and PDMS
      membrane was dependent on dissolving vehicles and test concentrations. An
      enhanced permeation increase across piglet skin was found for DEET and oxybenzone
      when both compounds were present in the same medium (DEET: 289% in propylene
      glycol, 243% in ethanol and 112% in poly(ethylene glycol) (PEG-400); oxybenzone:
      139% in PEG-400, 120% in propylene glycol and 112% in ethanol). Permeation
      enhancement was also observed in PDMS membrane (DEET: 207% in ethanol, 124% in
      PEG-400 and 107% in propylene glycol; oxybenzone: 254% in PEG-400, 154% in
      ethanol and 105% in propylene glycol). PDMS membrane was found to be a suitable
      candidate for in-vitro diffusion evaluations. This study shows that the
      permeations of the insect repellent DEET and the sunscreen oxybenzone were
      synergistically enhanced when they were applied simultaneously.

PMID- 15142340
TI  - Disposition kinetics of taxanes after intraperitoneal administration in rats and
      influence of surfactant vehicles.
AB  - Rats were intraperitoneally administered 40 mg x kg(-1) of paclitaxel or
      docetaxel dissolved in various drug solutions. The drug solutions were prepared
      using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and
      1.5% Polysorbate-80 (PS-80) (TXT), 7.5% PS-80 (TXT+PS-80) or 4.2% crEL (TXT+crEL)
      for docetaxel. The apparent first-order absorption rate constant from the
      peritoneal cavity (k(a)) of TXL was about one-twentieth of that of TXT. The ratio
      of the area under the concentration-time curve of drug in plasma over that in
      ascites for TXL was about one-third of that of TXT. The values of the above ratio
      and the k(a) of TXT+PS-80 and TXT+crEL were similar to those of TXL. After
      intraperitoneal administration, the values of the blood-to-plasma concentration
      ratio in the four groups were similar and independent of time. In the in-vitro
      study, PS-80 and crEL caused similar, concentration-dependent decreases of drug
      permeation into red blood cells after a 15-min incubation of rat blood with 10
      microg x mL(-1) of TXL. We demonstrated that the disposition kinetics of taxanes
      after intraperitoneal administration to rats was strongly influenced, in a
      concentration-dependent manner, by the surfactant vehicle used, crEL or PS-80.

PMID- 15142341
TI  - Effects of protein-calorie malnutrition on the pharmacokinetics of DA-7867, a new
      oxazolidinone, in rats.
AB  - The pharmacokinetic parameters of DA-7867, a new oxazolidinone, were compared
      after intravenous and oral administration at a dose of 10 mg x kg(-1) to control
      rats and rats with protein-calorie malnutrition (rats with PCM). After
      intravenous administration of 10 mg x kg(-1) DA-7867 to rats, metabolism of the
      drug was not considerable and after 14 days approximately 85.0% of the dose was
      recovered as unchanged drug from urine and faeces. After intravenous
      administration to rats with PCM, the area under the plasma concentration-time
      curve from time zero to time infinity (AUC) was significantly smaller (10800 vs
      6990 microg min x mL(-1)) compared with control rats. This may have been due to
      significantly faster total body clearance (CL, 0.930 vs 1.44 mL x min(-1) x kg(
      1)). The faster CL in PCM rats could have been due to significantly faster non
      renal clearance (0.842 vs 1.39 mL x min(-1) x kg(-1) due to significantly greater
      gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867
      recovered from the entire gastrointestinal tract at 24 h was significantly
      greater (1.19 vs 4.28% of intravenous dose)) because the renal clearance was
      significantly slower in PCM rats (0.0874 vs 0.0553 mL x min(-1) x kg(-1)). After
      oral administration to PCM rats, the AUC was significantly smaller compared with
      control rats (7900 vs 4310 microg x min x mL(-1)). This could have been due to a
      decrease in absorption from the gastrointestinal tract.

PMID- 15142342
TI  - The plasma glucose lowering action of tetrandrine in streptozotocin-induced
      diabetic rats.
AB  - The effect of tetrandrine, an active principle of Stephaniae tetrandrae, on the
      plasma glucose level in streptozotocin-induced diabetic rats (STZ-diabetic rats)
      was investigated. A single intravenous injection of tetrandrine decreased the
      plasma glucose in a dose-dependent manner in STZ-diabetic rats. Moreover,
      tetrandrine (1.0 mg x kg(-1)) significantly attenuated the rise in plasma glucose
      induced by the intravenous glucose challenge test in normal rats. A stimulatory
      effect of tetrandrine on glucose uptake was obtained in soleus muscles isolated
      from STZ-diabetic rats with a concentration-dependent manner from 0.01 to 10.0
      micromol L(-1). The increase in glucose utilization by tetrandrine was further
      characterized using the enhancement of glycogen synthesis in the hepatocytes of
      STZ-diabetic rats. These results suggest that tetrandrine has the ability to
      enhance glucose utilization in peripheral tissue, resulting in the lowering of
      plasma glucose in diabetic rats lacking insulin.

PMID- 15142343
TI  - The antioxidant drink effective microorganism-X (EM-X) pre-treatment attenuates
      the loss of nigrostriatal dopaminergic neurons in 6-hydroxydopamine-lesion rat
      model of Parkinson's disease.
AB  - There is continued interest in the assessment and potential use of antioxidants
      as neuroprotective agents in diseases associated with increased oxidative stress,
      such as Parkinson's disease. The neuroprotective effect of a natural antioxidant
      drink, EM-X (a ferment derivative of unpolished rice, papaya and seaweeds with
      effective microorganisms), was investigated using the 6-hydroxydopamine (6-OHDA)
      lesion rat model of Parkinson's disease. The nigrostriatal dopaminergic neurons
      were unilaterally lesioned with 6-OHDA (8 microg) in rats that were treated with
      a 10-times diluted EM-X drink (dilEM-X), standard EM-X drink (stdEM-X) or tap
      water for 4 days. Seven days post lesion, the integrity (no. of tyrosine
      hydroxylase positive cells (TH+ cells) in the substantia nigra pars compacta
      (SNpc)) and functionality (dopamine and its metabolites DOPAC and HVA content in
      the striata) of nigrostriatal dopaminergic neurons were assessed. In the vehicle
      treated rats, infusion of 8 microg of 6-OHDA significantly reduced the number of
      TH+ cells in the SNpc as well as the levels of dopamine, DOPAC and HVA in the
      striata on the lesion side. The loss of TH+ cells, dopamine and HVA, but not the
      DOPAC levels, was significantly attenuated by stdEM-X pretreatment, but not by
      the dilEM-X pretreatment. There were no significant changes in the TH+ cells, or
      in the monoamine levels with the EM-X pretreatment per se, except for a small but
      significant fall in the levels of dopamine with the stdEM-X. The evidence
      presented supports the potential neuroprotective effects of stdEM-X drink,
      although its effect on dopamine levels needs further investigation.

PMID- 15142344
TI  - Investigations into the antinociceptive activity of Sapindus trifoliatus in
      various pain models.
AB  - The effect of the aqueous extract of Sapindus trifoliatus (ST) on chemical,
      thermal-induced pain, nitroglycerin-induced hyperalgesia and pain on inflamed
      tissue was investigated. The extract (20 and 100 mg x kg(-1), i.p.) significantly
      inhibited acetic-acid-induced abdominal constrictions, formalin-induced pain
      licking and hotplate-induced pain in mice. Furthermore, the extract significantly
      increased the response latencies of nitroglycerin-induced hyperalgesia by the
      tail-flick method and mechanical pain on carrageenan-induced inflamed paw in
      rats. The data suggest that ST has an inhibitory activity on both peripheral and
      central pain mechanisms and has a modulatory role in NO-mediated nociceptive
      transmission.

PMID- 15142345
TI  - Trypanocidal and antifungal activities of p-hydroxyacetophenone derivatives from
      Calea uniflora (Heliantheae, Asteraceae).
AB  - The dichloromethane extract of underground parts of Calea uniflora (Heliantheae,
      Asteraceae) exhibited trypanocidal and antifungal activities. Four p
      hydroxyacetophenone derivatives were isolated as the main compounds: 2-senecioyl
      4-(hydroxyethyl)-phenol (1), 2-senecioyl-4-(angeloyloxy-ethyl)-phenol (2), and
      two new derivatives, 2-senecioyl-4-(methoxyethyl)-phenol (3) and 2-senecioyl-4
      (pentadecanoyloxyethyl)-phenol (4). 1 and 4 were active towards Trypanosoma cruzi
      trypomastigotes, reducing their number by 70 and 71% at 500 microg x mL(-1),
      whereas 2 and 3 were inactive. All the compounds tested showed antifungal
      activity with minimal inhibitory concentration values between 500 and 1000 microg
      x mL(-1) against pathogenic Candida spp. and dermatophytes. The isolation,
      structure elucidation, NMR spectral assignments and bioactivity results of these
      compounds are reported.

PMID- 15142346
TI  - Chronic caffeine intake affects lysozyme activity and immune cells in mice.
AB  - The aim of this study was to examine the effect of caffeine on the activity of
      lysozyme and some immune parameters of mice. The mice were divided into five
      groups. Group 1, the control group, was given water. The other four groups were
      administered various concentrations of caffeine by oral intubation (group 2, 2 mg
      x kg(-1); group 3, 20 mg x kg(-1); group 4, 40 mg x kg(-1); group 5, 200 mg x kg(
      1)). It was found that the activity of lysozyme in the serum depended on the
      caffeine dose. Compared with the control (group 1), lysozyme activity was 1.4
      times higher in group 2, 1.6-times higher in the group 3, and 1.8-times higher in
      groups 4 and 5 (P < 0.05). In group 3 a significant increase in spleen weight was
      detected and the spleen index was 2.1-times (P < 0.05) higher compared with
      control. In group 3 the number of monocytes and neutrophils was 2.5-times higher
      (P < 0.05) compared with control. In group 5 the caffeine increased the number of
      neutrophils 2.7-times and increased the number of eosinophils 4.6-times (P <
      0.05) compared with control. Our study revealed that caffeine played an important
      role in the development of protective immune response.

PMID- 15142347
TI  - Melissa officinalis L. essential oil: antitumoral and antioxidant activities.
AB  - Melissa officinalis L (lemon balm) is a traditional herbal medicine used widely
      as a mild sedative, spasmolytic and antibacterial agent. This paper focuses on
      the analysis of the chemical composition and the biological activities of M.
      officinalis essential oil obtained under controlled harvesting and drying
      conditions. An in-vitro cytotoxicity assay using MTT indicated that this oil was
      very effective against a series of human cancer cell lines (A549, MCF-7, Caco-2,
      HL-60, K562) and a mouse cell line (B16F10). This oil possessed antioxidant
      activity, as evidenced by reduction of 1,1-diphenyl-2-picryl-hydrazyl (DPPH).
      These results pointed to the potential use of M. officinalis essential oil as an
      antitumoral agent.

PMID- 15142348
TI  - Absorption of phenolsulfonphthalein as a model across the mesenteric surface in
      rats to determine the drug absorption route after intraperitoneal administration.
AB  - The purpose of this study was to clarify the absorption characteristics of a drug
      across the mesenteric surface, which occupies a large area of absorption in the
      peritoneal cavity, in order to determine the drug absorption route after
      intraperitoneal administration. Absorption of phenolsulfonphthalein (PSP) as a
      model after application to the mesenteric surface was investigated in rats by
      employing a cylindrical diffusion cell attached to the mesentery with or without
      blood vessels. PSP was absorbed from the rat mesenteric surface, followed by its
      appearance in the plasma and bile, regardless of blood vessel existence. The
      absorption ratios of PSP in 6 h were calculated to be 92.1 and 83.6% from the
      mesenteric surface with and without blood vessels, respectively. We then employed
      an experimental system in which a polyethylene (PE) cap was stuck on the surface
      of the other side to exclude the influence of absorption of the drug from the
      other organ surfaces that penetrated across the mesentery. The PE cap decreased
      the appearance of PSP in the plasma from the mesenteric surface with blood
      vessels and eliminated the PSP absorption completely from the mesenteric surface
      without blood vessels. Accordingly, blood vessels on the mesenteric surface must
      actually play an important role in drug absorption, but the contribution of the
      mesenteric surface to drug absorption from the peritoneal cavity is unlikely to
      be significant because there is a small effective area of blood vessels.

PMID- 15142349
TI  - CD4+ T-cell recovery and clinical outcome in HIV-1-infected patients exposed to
      multiple antiretroviral regimens: partial control of viremia is associated with
      favorable outcome.
AB  - The goal of antiretroviral therapy is clinical benefit through the suppression of
      viral replication and the immunologic reconstitution of HIV-1-infected patients.
      In spite of the availability of different highly active antiretroviral therapy
      only some patients sustain undetectable plasma viremia. We performed an
      observational study from October 1987 to February 2001 on immunologic and
      clinical outcome of 148 HIV-1-infected patients from an open clinical cohort at
      Sao Paulo University, Brazil. The median T CD4+ at starting first monitored
      regimen was 227 cells per microliter, with 65% of patients previously exposed to
      antiretroviral regimens, mostly dual therapy. Virologic response to
      antiretroviral therapy, after a median period of 179 weeks of monitored
      treatment, allowed classifying patients as aviremic (RNA plasma viremia below 500
      copies per milliliter); viremic (current viral load at historic levels), and
      viremic-attenuated groups (detectable viremia, but > 1 log viral suppression).
      HIV RNA viral load, T CD4+ cells count, HIV-1 pol sequencing, inflammatory
      parameters, and clinical events were documented during a median follow-up of 251
      weeks. This study observed better clinical and immunologic responses in the
      aviremic group, but the viremic-attenuated group showed a significant gain in
      CD4+ cells (p < 0.013) and a decreased number of cases progressing to an AIDS
      defining clinical condition (p < 0.001) compared to the viremic group.

PMID- 15142350
TI  - Cross-resistance patterns among HIV protease inhibitors.
AB  - Acquired resistance to antiretroviral agents is an established sequela of HIV
      pharmacotherapy. Viral mutations can confer reduced susceptibility to
      antiretroviral medications, resulting in virologic and clinical failure in more
      than half of treated patients. Cross-resistance that can develop within each drug
      class leads to the progressive loss of future therapeutic options for individual
      patients. Although protease inhibitors (PIs) are a potent class of
      antiretrovirals, resistance can still develop rapidly, and multiple-PI resistance
      has become a serious, growing clinical problem. Development of rational treatment
      strategies that recognize specific patterns of cross-resistance among PIs are
      needed to help clinicians choose the most appropriate PI. Rational sequencing of
      PI use should be based on genotypic and phenotypic resistance testing.
      Maintaining higher drug plasma levels or using specific PI combinations may also
      diminish PI cross-resistance. New agents that are less likely to induce or be
      susceptible to cross-resistance will be of value in HIV treatment. This article
      reviews the acquisition of resistance to currently available PIs, discussing the
      drug-specific mutational patterns and evidence of clinical cross-resistance. The
      resistance profiles of two newer PIs, atazanavir and tipranavir, are also
      presented.

PMID- 15142351
TI  - Tuberculosis infection in HIV-infected Indian patients.
AB  - Individuals with HIV infection are at increased risk for tuberculosis (TB). The
      altered CD4 T-cell homeostasis induced by HIV infection may play a key role in
      the development of tuberculosis in HIV-infected patients. In this retrospective
      analysis, lymphocyte profiles (CD4 and CD8 count) of subjects infected with HIV,
      with or without TB, were evaluated. The influence of tuberculosis treatment on
      the CD4 count in dually infected patients was analyzed in a subset of patients
      available for follow-up. Of 421 subjects with HIV infection studied, 105 (24.9%)
      were positive for TB (HIV+TB+). A statistically significant difference (p =
      0.0001) was found in the median CD4+ counts between the HIV+TB- (297.5 per
      microliter) and HIV+TB+ (181 per microliter) groups. TB was found to be the
      indicator disease for HIV infection in 36 (34.2%). In 65.7% of HIV-infected
      patients, TB was the first AIDS-defining disease. Of 72 patients who were
      receiving TB treatment, 33 (45.9%) showed an increase in CD4 counts, but this was
      statistically not significant. None of these patients was undergoing
      antiretroviral therapy prior to TB treatment. We conclude from this retrospective
      study that TB, a common HIV-related opportunistic infection in Indian subjects,
      is associated with lower CD4+ counts. The influence of TB therapy on CD4 counts
      in the patients needs to be further investigated.

PMID- 15142352
TI  - Medicinal and recreational marijuana use by patients infected with HIV.
AB  - The goal of this study was to describe and compare the prevalence, predictors and
      patterns of marijuana use, specifically medicinal marijuana use among patients
      with HIV in Ontario, Canada. Any marijuana use in the year prior to interview and
      self-defined medicinal use were evaluated. A cross-sectional multicenter survey
      and retrospective chart review were conducted between 1999 and 2001 to evaluate
      overall drug utilization in HIV, including marijuana use. HIV-positive adults
      were identified through the HIV Ontario Observational Database (HOOD), 104
      consenting patients were interviewed. Forty-three percent of patients reported
      any marijuana use, while 29% reported medicinal use. Reasons for use were similar
      by gender although a significantly higher number of women used marijuana for pain
      management. Overall, the most commonly reported reason for medicinal marijuana
      use was appetite stimulation/weight gain. Whereas male gender and history of
      intravenous drug use were predictive of any marijuana use, only household income
      less than $20,000 CDN was associated with medicinal marijuana use. Age, gender,
      HIV clinical status, antiretroviral use, and history of intravenous drug use were
      not significant predictors of medicinal marijuana use. Despite the frequency of
      medicinal use, minimal changes in the pattern of marijuana use upon HIV diagnosis
      were reported with 80% of current medicinal users also indicating recreational
      consumption. Although a large proportion of patients report medicinal marijuana
      use, overlap between medical and recreational consumption is substantial. The
      role of poverty in patient choice of medicinal marijuana despite access to care
      and the large proportion of women using marijuana for pain constitute areas for
      further study.

PMID- 15142353
TI  - Brief motivational interviewing to improve adherence to antiretroviral therapy:
      development and qualitative pilot assessment of an intervention.
AB  - Because successful HIV treatment requires exceptional adherence to antiretroviral
      therapy (ART), interventions to improve ART adherence are essential. We developed
      and pilot-tested an intervention to improve ART adherence, based on brief
      motivational interviewing (MI), which has successfully improved selected health
      behaviors but has not been tested for ART adherence. We administered the 15- to
      30-minute MI session to 20 HIV-positive adults and assessed its usefulness and
      relevance. Then, we content-analyzed the session for HIV care issues and
      strategies most salient to patients in the MI session. During the session, all
      participants chose an HIV-care-related topic that they wanted to discuss, and
      talked about issues, barriers, and facilitators related to their topic. Most
      participants (70%) developed strategies to help improve their health. Questions
      asked after the MI session revealed that almost all (95%-100%) participants found
      the session useful and helpful. This theoretically based, empowering health
      counseling approach for HIV-positive persons warrants further research.

PMID- 15142354
TI  - Hepatitis C treatment eligibility in an urban population with and without HIV
      coinfection.
AB  - In an urban referral clinic, 182 hepatitis C-infected adults including 110 (60%)
      with HIV coinfection were evaluated for pegylated interferon and ribavirin
      therapy. Overall, only 33% were eligible for treatment. Considering all patients
      together, the major barriers to treatment were nonadherence with the evaluation
      process (23%), refusal of treatment (10%), active substance abuse (9%), and
      medical contraindication (8%). There was a trend toward a higher rate of
      treatment eligibility in HIV coinfected patients (39% vs. 25%; p = 0.07), who
      were significantly more likely to be adherent with the evaluation process
      compared to those with hepatitis C alone (86% vs. 63%; p = <0.001). Acceptance of
      antiviral therapy for hepatitis C was similar between eligible persons with and
      without HIV. These findings highlight the need to develop interventions to
      improve adherence and to manage substance abuse and other comorbidities in order
      to maximize the impact of interferon and ribavirin therapy on urban patients with
      hepatitis C.

PMID- 15142355
TI  - More data on D-D4FC.

PMID- 15142356
TI  - Drug combination treats HIV and HCV.

PMID- 15142357
TI  - Combined levotriiodothyronine and levothyroxine therapy for hypothyroidism: are
      we a step closer to the magic formula?

PMID- 15142358
TI  - Thyrocytes isolated from autoimmune-diseased thyroids secrete soluble tumor
      necrosis factor-R1 that is related to their elevated protein kinase C activity.
AB  - Soluble tumor necrosis factor (TNF)-alpha receptors have the potential to
      modulate TNF-alpha activity during autoimmune thyroiditis. In this study we
      examined cell-surface TNF-alpha receptors and soluble TNF-alpha receptor
      production by thyrocytes from normal and MRL-lpr(-/-) (diseased) mice, which
      spontaneously develop autoimmune thyroiditis. We found that murine thyrocytes
      possess the 55-kd receptor (TNF-R1). Examination of soluble TNF-R1 production
      revealed that diseased thyrocytes produced sevenfold more soluble TNF-R1 than
      normal thyrocytes. Furthermore, basal protein kinase C (pKC) activity in diseased
      thyrocytes was 67% higher than that found in normal murine thyrocytes. The
      elevated basal pKC activity in diseased thyrocytes was related to their enhanced
      production of soluble TNF-R1 because inhibition of pKC activity with calphostin C
      caused soluble TNF-R1 production to decrease significantly. Additionally, soluble
      TNF-R1 production by murine thyrocytes was not a result of cell-surface receptor
      shedding but through secretion of a truncated version of TNF-R1. This was evident
      when cell-surface TNF-R1 levels were unchanged after treatment of diseased
      thyrocytes with calphostin C. Also, the 28-kd form of TNF-R1, which corresponds
      to the soluble receptor, was present in the intracellular membranes of the
      diseased thyrocytes.

PMID- 15142359
TI  - Doxorubicin induces Fas-mediated apoptosis in human thyroid carcinoma cells.
AB  - Doxorubicin remains the most extensively used drug in the chemotherapy of thyroid
      cancer. However, drug resistance often limits the efficacy of chemotherapy in
      clinical practice. Several anticancer drugs exert their cytotoxic effect by
      triggering Fas-mediated apoptosis in some cell types. However, no investigations
      have been conducted to determine whether doxorubicin causes apoptosis in thyroid
      carcinomas. In the present study, we assessed the cytotoxic and apoptotic effects
      of doxorubicin on two thyroid cancer cell lines (FTC 238 and FTC 133). Cytotoxic
      effects of doxorubicin were evaluated by a 3-(4,5 dimethylthiazol-2yl) 2-5
      diphenyltetrazolium bromide (MTT) assay. Apoptosis was quantified by fluorescein
      isothiocyanate-conjugated annexin V/flow cytometric analysis and by DNA
      fragmentation. Fas expression was measured by flow cytometric analysis. After a
      24-hour incubation, doxorubicin induces a dose-dependent cytotoxicity in the two
      cell lines. Treatment with doxorubicin (0.5 and 1 microM) for 24 hours induced
      cell apoptosis and upregulated Fas expression. A significant correlation was
      found between the fluorescence intensity values obtained with annexin V staining
      and those observed for Fas expression (r = 0.996; p < 0.001 or r = 0.957; 0.02 <
      p < 0.05 for FTC 238 or FTC 133 cells, respectively). In conclusion, doxorubicin
      exerts its cytotoxic effects, at least partly, through Fas-mediated apoptosis in
      thyroid cancer cells. These results may have clinical implications for thyroid
      cancer therapy.

PMID- 15142360
TI  - Thyroxine plus low-dose, slow-release triiodothyronine replacement in
      hypothyroidism: proof of principle.
AB  - Studies in hypothyroid rats show that, when infused with a combination of
      thyroxine (T4) plus triiodothyronine (T3) to normalize thyrotropin (TSH),
      euthyroidism in all organs is only ensured when T(4) and T(3) are administered in
      a ratio as normally secreted by the rat thyroid. As substitution with T(4)-only
      results in an abnormal serum T(4)/T(3) ratio, it is also possible that in humans,
      euthyroidism does not exist at the tissue level in many organs, considering that
      iodothyronine metabolism in the human and the rat share many similar mechanisms.
      Recent reports in which cognitive function and well-being are compared in
      patients with primary hypothyroidism substituted with T(4)-only versus
      substitution with T(4) plus T(3) result in controversial findings in that either
      positive or no effects were found. In all these studies T(3) was used in the
      plain form that results in nonphysiologic serum T(3) peaks. In these studies it
      is suggested that substitution with T(3 )should preferably be performed with a
      preparation that slowly releases T(3) to avoid these peaks. In the study reported
      here we show that treatment of hypothyroid subjects with a combination of T(4)
      plus slow-release T(3) leads to a considerable improvement of serum T(4) and T(3)
      values, the T(4)/T(3) ratio and serum TSH as compared to treatment with T(4)-
      only. Serum T(3) administration with slow-release T(3) did not show serum peaks,
      in contrast to plain T(3).

PMID- 15142361
TI  - Descriptive epidemiology of thyroid carcinoma in Carinthia, Austria: 1984-2001.
      Histopathologic features and tumor classification of 734 cases under elevated
      general iodination of table salt since 1990: population-based age-stratified
      analysis on thyroid carcinoma incidence.
AB  - INTRODUCTION: The aim of the study was to investigate the current thyroid
      carcinoma (TC) incidence in Carinthia, a former iodine-deficient, goiter-endemic
      region in Austria with approximately 550,000 inhabitants from 1984 to 2001. Using
      age-cohort analysis we analyzed the TC incidence under the impact of two regional
      risk factors: the contamination of Austrian soils by the radioactive fallout in
      from Chernobyl 1986 and the increased iodination of table salt in a general
      program of goiter prophylaxis begun in 1991. To evaluate the characteristics of
      TC incidence, we compared the results of the periods 1984-1989, 1990-1995, and
      1996-2001. RESULTS: A total of 734 TC cases were diagnosed. Papillary,
      follicular, medullary, oxyphilic, and anaplastic TC accounted for 76%, 18%, 3%,
      1%, and 2%, respectively. The female to male ratio was 3:1. The annual incidence
      rate increased by 8.05% in females and 11.6% in males. TC cases younger than 40
      years of age accounted for 22.6%, with a rate increase of 18% per year in young
      males, the female-to-male ratio decreased from 8.3, 6.1, 2.7 younger than 40 in
      the compared periods. Along with a further increase in papillary TC incidence and
      papillary thyroid carcinoma (PTC) follicular thyroid carcinoma (FTC) ratio in the
      adult population, the ratio tended to decrease in the younger than 40-year-old
      population. T4 class TC and loco-regional lymph node involvement increased
      significantly. INTERPRETATION: The observed changes in TC incidence, particularly
      in the young population, as in adults, could be linked to the abovementioned risk
      factors involved in the initiation and early growth of TC, and iodine may play a
      role in stimulating overall thyroid activity.

PMID- 15142362
TI  - Practice, efficacy, and costs of thyroid nodule evaluation: a retrospective study
      in a Dutch university hospital.
AB  - Fine-needle aspiration (FNA) of thyroid nodules has markedly reduced the role of
      thyroid scintigraphy. This is often limited to nondiagnostic or follicular
      (tumor) FNA classifications. In this study, we evaluated the efficacy and cost of
      such a strategy in a university center. From 1992-1998, 995 aspirations were done
      in 667 patients with palpable nodules. FNA was classified as malignant,
      suspicious, follicular, benign or inadequate. The Gold standard was surgery or
      extended follow-up, including physical examination, FNA, and/or ultrasound (US)
      with a time interval of half a year. Cost analysis was limited to operated
      patients. The first FNA yielded inadequate results in 28%, decreasing to 6% after
      4 aspirations (n = 42). The other final classifications were: 76%, benign; 14%,
      follicular; 2%, suspicious; 1%, malignant (n = 7). Scintigraphy ((99m)Tc)
      suggested a hyperfunctioning autonomous nodule (adenoma) in 12% and 3% of the
      inadequate and follicular subset, respectively. Surgery for diagnostic reasons (n
      = 105) yielded 24 malignancies (23%): in 47% of suspicious, 12% of the
      follicular, and in all with malignant FNA. Postoperative morbidity occurred in 14
      (5 laryngeal nerve paralyses) with benign histology. Major cost drivers were
      surgery and hospitalization: mean costs per patient amounting to Euro 3.311 in
      case of benign histology. We conclude that current work-up is still unable to
      prevent unnecessary surgery for benign thyroid nodules. Thyroid scintigraphy
      proved most productive in the inadequate FNA category. Improvement of the
      diagnostic process using immunohistochemistry and/or imaging is needed from the
      patient's and society's perspective.

PMID- 15142363
TI  - Evaluation of a coated-tube assay for antithyrotropin receptor antibodies in
      patients with Graves' disease and other thyroid disorders.
AB  - The detection of autoantibodies to the thyrotropin-receptor antibody (TRAb) is
      commonly used in clinical practice for the diagnostic assessment of Graves'
      disease (GD) and its differential diagnosis from toxic multinodular goiter (MNG)
      and autonomous adenoma. Additionally, TRAb assays can be useful during
      antithyroid drug treatment of GD to evaluate the risk of relapse and/or
      remission. The detection of TRAb was originally performed using a radioreceptor
      assay based on detergent-solubilized porcine thyroid membranes (TRAb). More
      recently new assays using purified porcine or recombinant human thyrotropin (TSH)
      receptor-coated plastic tubes (CT) have been developed (pCT-TRAb or hCT-TRAb). We
      have evaluated both assays (TRAb and pCTTRAb) in 300 individuals: healthy
      controls (n = 51); patients with GD before and after treatment (n = 200),
      patients with MNG (n = 29), and Hashimoto's thyroiditis [HT; n = 20]). All
      healthy controls and patients with HT had undetectable TRAb using both methods.
      Patients with active (not treated) GD had higher pCT-TRAb values (mean +/-
      standard deviation [SD], 58.2% +/- 20.3%, inhibition of TSH binding) compared to
      TRAb (41.2% +/- 15.4%, p < 0.01, Wilcoxon test). Results (as percent inhibition
      for both methods) had a positive and significant correlation (r = 0.68, p <
      0.001). Moreover TRAb assay had a 97.3% sensitivity and 96.8% specificity; the
      pCT-TRAb sensitivity was 96.3% and specificity was 98.4% at a cutoff of 1.51 U/L.
      During treatment of GD, the TRAb method resulted in significantly lower (p <
      0.05) values at 12, 24, and 30 months, while pCT-TRAb only exhibited significancy
      (compared to basal levels) at 30 months. The percent inhibition after 131I
      treatment of GD was significantly higher for pCT-TRAb (33.7 +/- 25.7) compared to
      TRAb (21.9 +/- 17.7, p < 0.01, Wilcoxon test). Only one patient with untreated
      MNG had a positive pCT-TRAb but negative TRAb value. Patients with MNG treated
      with 131I were divided into two groups: group 1 (only (131)I) or group 2 (hrTSH
      preceding (131)I). After MNG radioisotopic ablation, five patients had a positive
      pCT-TRAb and four had a positive TRAb (group 1) while in group 2, three patients
      had a positive pCT-TRAb and two had a positive TRAb assay. In conclusion, pCT
      TRAb usually had higher percent inhibition values compared to TRAb in untreated
      GD, had a relatively lower decrease in percent inhibition values during treatment
      but exhibited a slightly increased sensitivity compared to TRAb. An advantage of
      the pCT-TRAb assay may be because of the coating system itself that might expose
      more receptor sites for the antibody.

PMID- 15142364
TI  - Prognostic value of thyroglobulin serum levels and 131I whole-body scan after
      initial treatment of low-risk differentiated thyroid cancer.
AB  - Diagnostic iodine-131 whole-body scan ((131)I-WBS) and serum thyroglobulin values
      (Tg) performed 6 to 12 months after thyroid ablation for differentiated thyroid
      carcinoma were evaluated in 194 consecutive patients at the Hospital de Navarra,
      (Pamplona, Spain). All patients underwent near-total thyroidectomy and (131)I
      ablation with 3.7 GBq. Patients with positive anti-Tg antibodies or with (131)I
      uptake outside the neck were previously excluded. Uptake of (131)I in the thyroid
      bed was detected in 27 patients (13.9%). Serum Tg levels were below 0.5 ng/mL in
      133 patients, ranged from 0.5-10 ng/mL in 39 patients, and was above 10 ng/mL in
      22 patients. After a follow-up of 7.7 +/- 3.3 years, persistence of the illness
      has been observed in 2 patients with undetectable Tg (1.5%), but metastases were
      not detected in any case. In those with Tg higher than 0.5 ng/mL, 29 of 61
      patients had persistence of the disease (47.5%) with evidence of metastases in 15
      (24.5%), irrespective of the initial total body scan (131)I uptake. In
      conclusion, serum Tg levels obtained after thyroid ablation has a good prognostic
      value and permits the selection of patients for further diagnostic studies, while
      diagnostic (131)I-WBS performed at that time did not correlate with results of Tg
      and scarcely provides additional information.

PMID- 15142365
TI  - A case of thymic enlargement in hyperthyroidism in a young woman.
AB  - We present the case of a 24-year-old woman with thymic enlargement accompanied by
      hyperthyroidism. An x-ray incidentally detected her thymic enlargement and the
      size was estimated to be 226 cm(3) by computed tomography (CT) using three
      dimensional analysis. Physical examination revealed a soft diffuse goiter,
      increased sweating and restlessness; thyroid function tests showed
      hyperthyroidism. Because the possibility of a thymoma could not be completely
      excluded, a mediastinal biopsy via a supracervical approach was done that
      determined the specimen was composed of normal thymic tissue. Together with these
      findings, the patient's thymic enlargement was likely to be consistent with true
      thymic hyperplasia. Moreover, we have demonstrated the presence of the
      thyrotropin (TSH) receptor in her thymus using reverse transcription-polymerase
      chain reaction (RT-PCR). She was treated with methimazole, resulting in the
      resolution of not only the thyroid dysfunction but also thymic enlargement.
      Thymic enlargement has often been recognized as a complication of
      hyperthyroidism. However, the pathophysiologic mechanisms underlying these
      conditions remain obscure. Our result raises the speculation that the thymus is
      also a target organ of autoimmune attack as are the orbital and fibroblasts,
      which lead to Graves' ophthalmopathy and pretibial dermopathy, respectively.

PMID- 15142366
TI  - Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and
      insulin resistance.
AB  - The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus,
      and weight gain. On magnetic resonance imaging (MRI) she was found to have severe
      primary hypothyroidism and a large pituitary mass. In addition, acanthosis
      nigricans, obesity, and hyperinsulinism were observed. Findings were similar in
      three of four siblings. Thyroid peroxidase antibodies were detected in the father
      and three of four siblings. Although all family members were obese, and
      hyperinsulinemia with high proinsulin and C-peptide was found in all except one
      sibling, only the mother and one child had overt type 2 diabetes mellitus.
      Because of the unusual association of autoimmune thyroid disease, insulin
      resistance and obesity rather than insulin deficiency, we searched for possible
      genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune
      thyroid disease or insulin resistance. Mutational analysis of known obesity genes
      was done. Leptin was not deficient, and sequencing of the proband's DNA showed no
      mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR
      gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited
      diabetes and deafness was ruled out since no mutations were found in mitochondria
      DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably
      high incidence of childhood autoimmune hypothyroidism, pituitary enlargement,
      insulin resistance and obesity in this family is not linked to known HLA types or
      known gene defects.

PMID- 15142367
TI  - Functional lingual thyroid as unusual cause of progressive Dysphagia.
AB  - Lingual thyroid is an uncommon developmental anomaly and is the result of failure
      of the thyroid to descend from the foramen caecum to its prelaryngeal site. The
      lingual thyroid with a functioning thyroid gland in the neck is even more rare.
      In this report, we describe a 40-year-old female patient with a foreign body
      sensation and progressive dysphagia caused by ectopic lingual thyroid that is 5 x
      4 x 3 cm in size. Here we present a patient with functional lingual thyroid gland
      who had had thyroidectomy 20 years ago. Lingual thyroid, which is like a
      malignant mass, was excised by external approach without complications.

PMID- 15142368
TI  - Parathyroid cyst.

PMID- 15142369
TI  - Dietary iodine in pregnant women from the Boston, Massachusetts area.

PMID- 15142370
TI  - The RET IVS1-126G>T variant is strongly associated with the development of
      sporadic medullary thyroid cancer.

PMID- 15142371
TI  - Thyroid disease and reproductive health.

PMID- 15142372
TI  - Thyroid dysfunction and women's reproductive health.
AB  - Thyroid dysfunction is extremely common in women and has unique consequences
      related to menstrual cyclicity and reproduction. Even minimal hypothyroidism can
      increase rates of miscarriage and fetal death and may also have adverse effects
      on later cognitive development of the offspring. Hyperthyroidism during pregnancy
      may also have adverse consequences. Accordingly, thyrotropin (TSH) determination
      is warranted for all women planning pregnancy or those already pregnant.
      Replacement doses should be carefully monitored throughout pregnancy because the
      increased renal iodine loss and estrogen-induced rise in thyroxine-binding
      globulin (TBG) often result in a higher dose requirement. Although thyroid
      abnormalities are part of the standard differential diagnosis of menstrual
      disorders, recent studies indicate that these are relatively infrequent causes.
      Nonetheless, TSH is still required as part of the laboratory evaluation of women
      with abnormal cycles. The incidence of postpartum thyroiditis is high--6%-8% in
      various studies. A TSH should be performed in all postpartum patients who are
      depressed, who complain of unusual fatigue or anxiety or have any of the
      classical symptoms of hyperthyroidism or hypothyroidism. Practitioners providing
      health care for women should be alert to thyroid disorders as possible
      etiological factors in nonspecific symptoms such as fatigue and depression.
      However, most women with these symptoms are euthyroid; replacement therapy for
      them is not indicated. The long-standing dogma of thyroidology that replacement
      with levothyroxine alone is satisfactory for all hypothyroid patients has
      recently been questioned but results of trials are inconclusive. Nonetheless,
      satisfactory regimens can be found for the vast majority of patients.

PMID- 15142373
TI  - The interrelationships between thyroid dysfunction and hypogonadism in men and
      boys.
AB  - Thyroid hormone deficiency affects all tissues of the body, including multiple
      endocrine changes that alter growth hormone, corticotrophin, glucocorticoids, and
      gonadal function. Primary hypothyroidism is associated with hypogonadotropic
      hypogonadism, which is reversible with thyroid hormone replacement therapy. In
      male children follicle-stimulating hormone (FSH) is elevated and associated with
      testicular enlargement without virilization. Men with primary hypothyroidism have
      subnormal responses of luteinizing hormone (LH) to gonadotropin-releasing hormone
      (GnRH) administration and normal response to human chorionic gonadotropin (hCG).
      Free testosterone concentrations are reduced in men with primary hypothyroidism
      and thyroid hormone replacement normalizes free testosterone concentrations. In
      men with primary hypothyroidism, prolactin is not consistently elevated (except
      in men and children with longstanding severe primary hypothyroidism), but
      prolactin declines following thyroid hormone replacement therapy. Thyroid hormone
      is known to affect sex hormone-binding hormonal globulin (SHBG) concentrations.
      Men with hyperthyroidism have elevated concentrations of testosterone and SHBG.
      Thyroid hormone therapy in normal men may also duplicate this elevation. In
      addition estradiol elevations are observed in men with hyperthyroidism, and
      gynecomastia is common in them as well. In contrast to patients with primary
      hypothyroidism, men with hyperthyroidism exhibit hyperresponsiveness of LH to
      GnRH administration and subnormal responses to hCG. Radioactive iodine therapy
      (RAI) of men treated for thyroid cancer produces a dose-dependent impairment of
      spermatogenesis and elevation of FSH up to approximately 2 years. Permanent
      testicular germ cell damage may occur in men treated with high doses of RAI. RAI
      commonly increases serum concentrations of FSH and LH while reducing inhibin B
      levels without affecting serum concentrations of testosterone. Thus, radioiodine
      therapy transiently impairs both germinal and Leydig cell function that usually
      recover by 18 months posttherapy.

PMID- 15142374
TI  - Interaction of estrogen therapy and thyroid hormone replacement in postmenopausal
      women.
AB  - Based on the use of estrogen therapy/hormone therapy (ET/HT) in postmenopausal
      women and the prevalence of hypothyroidism in this population, it is estimated
      that approximately 5% of all postmenopausal women receive treatment with both
      ET/HT and thyroid hormone replacement. Hormone therapy generally refers to the
      combined use of estrogens and progestins, the latter administered on a continuous
      or intermittent basis. HT is indicated for the treatment of postmenopausal women
      with intact uteri, whereas ET is used in women who have had hysterectomies.
      Because of its hepatic first-pass effect, oral estrogen therapy, the most
      commonly used modality of ET/HT, raises the circulating levels of thyroxine
      binding globulin (TBG), thereby increasing the bound fraction and decreasing the
      free (bioactive) fraction of circulating thyroxine (T(4)). As a consequence, oral
      ET/HT may increase the T(4) dosage requirements of women being treated for
      primary hypothyroidism as well as alter the pituitary-thyroid axis in euthyroid
      women. This paper reviews the potential interaction between ET/HT and thyroid
      hormone replacement based on the prevalence of their concomitant use, mechanistic
      aspects of the interaction, and recent clinical studies of the effects of oral ET
      in euthyroid and hypothyroid women. Other agents known to interact with thyroid
      hormone replacement, including soy supplements, are also reviewed. Because
      transdermal ET does not affect TBG levels and would not be expected to alter
      thyroid function, it may be a preferable modality for postmenopausal women who
      require concomitant treatment with ET/HT and T(4).

PMID- 15142376
TI  - HIV-1: a look back from 20 years.

PMID- 15142377
TI  - Partner molecules of accessory protein Vpr of the human immunodeficiency virus
      type 1.
AB  - Vpr (Viral protein-R) of the Human Immunodeficiency Virus type-1 is a 14-kDa
      virion-associated protein, conserved in HIV-1, -2 and the Simian Immunodeficiency
      Virus (SIV). Vpr is incorporated into the virion, travels to the nucleus, and has
      multiple activities including promoter activation, cell cycle arrest at the G2/M
      transition and apoptosis induction. Through these activities, Vpr is thought to
      influence not only viral replication but also numerous host cell functions. These
      functions may be categorized in three groups depending on the domains of Vpr that
      support them: (1) functions mediated by the amino terminal portion of Vpr, like
      virion packaging; (2) functions mediated by the carboxyl terminal portion such as
      cell cycle arrest; and (3) functions that depend on central alpha-helical
      structures such as transcriptional activation, apoptosis and subcellular
      shuttling. Association of these activities to specific regions of the Vpr
      molecule appears to correlate to the host/viral molecules that interact with
      corresponding portion of Vpr. They include Gag, host transcription
      factors/coactivators such as SP1, the glucocorticoid receptor, p300/CREB-binding
      protein and TFIIB, apoptotic adenine nucleotide translocator, cyclophilin A and
      14-3-3 proteins. The properties of Vpr molecule has made it difficult to assess
      its function and determine the true cellular interactors. Further studies on Vpr
      function are needed to fully assess the function of this important early
      regulatory molecule of HIV and other lentiviruses.

PMID- 15142378
TI  - HIV-1 Vpr: genetic diversity and functional features from the perspective of
      structure.
AB  - RNA viruses are well known for the enormous genetic variation. Retroviruses share
      this feature with other RNA viruses, and human immunodeficiency virus type 1 (HIV
      1) has been extensively investigated in this regard. Based on the DNA sequence
      analysis, HIV-1 has been classified into three groups; M, N, and O, with viral
      subtypes in each group. While the genetic variation between viral isolates has
      been documented throughout the genome, specifically, the env gene exhibits high
      variation. Analysis of the env gene from the sequential samples from HIV-1
      infected patients reveals variation in the range of 1% per year. The variation
      observed in individual HIV-1 genes in the form of changes at the nucleotide
      level, as expected, should result in one of the possible scenarios: (1) no change
      in the amino acid, (2) conservative change in the amino acid, (3) nonconservative
      change in the amino acid, and (4) premature stop codon resulting in a truncated
      protein. Hence, it is likely that the variation may impact on the function of the
      protein, depending on the nature of the mutation. The goal of this review is to
      summarize the polymorphisms in Vpr using the available sequence information and
      discuss their effects on the functions of Vpr from the point of view of its
      structure. The data generated by several groups provide a base for understanding
      the consequences of natural polymorphisms in specific regions of the Vpr
      molecule. However, it is also clear that secondary changes (second site or
      compensatory mutations) may modify the effect of a specific mutation and a
      comprehensive analysis is needed to delineate the role of specific residues in
      Vpr molecule. This is an area which, we hope, will attract investigators for
      further studies, and may provide information for understanding the molecular
      basis of Vpr functions.

PMID- 15142379
TI  - Heat-shock proteins reverse the G2 arrest caused by HIV-1 viral protein R.
AB  - HIV-1 Vpr is an important contributor to viral pathogenesis. Vpr displays several
      highly conserved pathogenic activities, including induction of cell cycle G(2)
      arrest and cell death. The host immune system, in turn, preferentially targets
      Vpr in an attempt to reduce its pathogenic effects. To identify innate anti-Vpr
      factors, we performed a genetic search for multicopy suppressors of Vpr-induced
      G(2) arrest in fission yeast. Several heat-shock proteins were identified in
      these experiments. Analyses in mammalian cells demonstrated that heatshock
      proteins HSP27 and HSP70 suppress Vpr-induced G2 arrest. This effect appears to
      be mediated by an interaction between heat shock proteins and Vpr. These results
      illustrate another example of antagonistic interactions between the viral and
      cellular proteins.

PMID- 15142380
TI  - Effects of HIV-1 Vpr on neuroinvasion and neuropathogenesis.
AB  - Human immunodeficiency virus type I (HIV-1) infection leads to penetration of the
      central nervous system (CNS) in virtually all infected individuals and HIV-1
      induced encephalopathy in a significant number of untreated patients. The
      molecular mechanisms by which HIV-1 enters the CNS and yields CNS dysfunction are
      still unclear. Our laboratories and others have begun to explore the direct
      effects of prioritized HIV-1-specific proteins on diverse human CNS cell types.
      One of these proteins, the accessory HIV-1 protein Vpr, is a critical moiety in
      these studies, and will be discussed in this article.

PMID- 15142381
TI  - HIV-1 Vpr and anti-inflammatory activity.
AB  - New and effective approaches for inflammatory diseases based on novel mechanisms
      of action are needed. One potential source of anti-inflammatory drugs exists
      among viruses. Viruses have evolved to infect, replicate within, and kill human
      cells through diverse mechanisms. They accomplish this fact by finding ways to
      out with the host's complex immune machinery. It is possible that the viral
      proteins and pathways involved in the downregulation of host immune function
      during infection can be exploited as a therapeutic in diseases that result in the
      overactivity of the immune system. Indeed, the human immunodeficiency virus type
      1 (HIV-1) protein, Vpr, affects cells in a number of ways that may prove useful
      for exploitation for the treatment of inflammatory diseases. Vpr has effects on T
      cell proliferation, cytokine production, chemokine production, and Nuclear Factor
      kappa B (NF-kappaB)-mediated transcription. Importantly, it has been observed
      that Vpr downregulates NF-kappaB and the production of pro-inflammatory cytokines
      such as TNF-alpha, and IL-12. These activities are worthy of further examination
      for control of hyperinflammatory and hyperproliferative conditions.

PMID- 15142382
TI  - Effect of HIV-1 Vpr on cell cycle regulators.
AB  - Cell cycle is one of the most complex processes in the life of a dividing cell.
      It involves numerous regulatory proteins, which direct the cell through a
      specific sequence of events for the production of two daughter cells. Cyclin
      dependent kinases (cdks), which complex with the cyclin proteins, are the main
      players in the cell cycle. They can regulate the progression of the cells through
      different stages regulated by several proteins including p53, p21(WAF1), p19,
      p16, and cdc25. Downstream targets of cyclin-cdk complexes include pRB and E2F. A
      cell cycle can be altered to the advantage of many viral agents, most notably
      polyomaviruses, papillomaviruses, adenoviruses, and retroviruses. In addition,
      viral protein R (Vpr) is a protein encoded by the human immunodeficiency virus
      type 1 (HIV-1). HIV-1, the causative agent of acquired immunodeficiency syndrome
      (AIDS), is a member of the lentivirus class of retroviruses. This accessory
      protein plays an important role in the regulation of the cell cycle by causing
      G(2) arrest and affecting cell cycle regulators. Vpr prevents infected cells from
      proliferating, and collaborates with the matrix protein (MA) to enable HIV-1 to
      enter the nucleus of nondividing cells. Studies from different labs including
      ours showed that Vpr affects the functions of cell cycle proteins, including p53
      and p21(WAF1). Thus, the replication of HIV-1, and ultimately its pathogenesis,
      are intrinsically tied to cell-cycle control.

PMID- 15142384
TI  - Psychopharmacology news.

PMID- 15142383
TI  - High-affinity interaction between HIV-1 Vpr and specific sequences that span the
      C/EBP and adjacent NF-kappaB sites within the HIV-1 LTR correlate with HIV-1
      associated dementia.
AB  - Numerous host and viral factors likely participate in the onset and progression
      of HIV-1-associated dementia (HIVD). Previous studies have suggested that viral
      gene expression in resident central nervous system (CNS) cells of
      monocyte/macrophage lineage play a central role in the production of neurotoxic
      viral proteins and infectious virus, deregulation of cellular gene expression,
      and/or dysfunction of glial and neuronal cell populations. HIV-1 replication is
      regulated, in part, by interactions between cellular transcription factors and
      the viral trans-activators, Tat and viral protein R (Vpr), with cis-acting
      promoter elements within the LTR. We have previously demonstrated that Vpr binds
      with high affinity to selected sequence configurations within CCAAT/enhancer
      binding protein (C/EBP) site I and downstream sequences immediately adjacent to
      this site. Studies reported herein establish a correlation between the diagnosis
      of HIVD and the increased prevalence of HIV-1 LTRs containing a C/EBP binding
      site I that exhibits high affinity for Vpr. To this end, the interaction of Vpr
      with C/EBP site I variants in 47 LTRs from three nondemented patients and 96 LTRs
      from seven demented patients was examined. Competition electrophoretic mobility
      shift (EMS) analyses were utilized to examine Vpr binding to oligonucleotide
      probes containing C/EBP site I variants. We demonstrated that 89% of LTRs derived
      from patients exhibiting clinical dementia contained C/EBP site I configurations
      that displayed a high relative affinity for Vpr, while only 11% of LTRs contained
      C/EBP site I configurations that exhibited a low relative affinity Vpr binding
      phenotype. In contrast, examination of LTRs derived from patients lacking
      clinically evident dementia revealed that only 53% of brain-derived LTRs
      contained C/EBP site I configurations that displayed a high relative affinity for
      Vpr, while 47% of LTRs contained C/EBP site I configurations that exhibited a low
      relative affinity Vpr binding phenotype. We propose that sequence-specific
      interactions between cis-acting elements in the LTR, members of the C/EBP family
      of transcription factors, and the virion-associated trans-activator protein Vpr
      play important roles in the pathogenesis of HIVD.

PMID- 15142385
TI  - Psychopharmacology in the school setting: therapeutic challenges in an adolescent
      with attention deficit hyperactivity disorder, possible bipolar disorder, and
      other comorbidity.

PMID- 15142387
TI  - 2002 annual reports: money and pharmaceuticals.

PMID- 15142388
TI  - Pharmacological treatment of adolescent major depression.
AB  - Antidepressant agents are widely prescribed for adolescents, although specific
      data regarding their efficacy in this age range are limited. The aims of the
      present article are to review research findings regarding the use of
      antidepressant drugs for adolescent depression and to discuss the main results in
      light of our clinical experience. Only 13 controlled trials on the use of
      antidepressant drugs for adolescent major depression are available in the
      literature. Six studies evaluated the efficacy of tricyclic antidepressants, yet
      they only included 196 adolescents altogether. Seven studies, including a total
      of 1,403 patients, evaluated the efficacy of three specific serotonin reuptake
      inhibitors: fluoxetine, paroxetine, and sertraline. Based on published data,
      serotonin reuptake inhibitors appear to be the first-line psychopharmacologic
      treatment for adolescent depression, as three compounds (fluoxetine, paroxetine,
      and sertraline) appeared to be effective in this indication. Conversely, all
      published studies failed to demonstrate that the tricyclic antidepressants were
      superior to placebo. Several questions remain open and are discussed: How should
      we use available scientific data in clinical practice? Are there nonspecific
      factors implicated in treatment response? Is there a serotonin hypothesis for
      juvenile depression? What are the priorities for future research?

PMID- 15142389
TI  - Fluoxetine in depressed AUD adolescents: a 1-year follow-up evaluation.
AB  - The authors conducted the first naturalistic 1-year follow-up evaluation of 10
      adolescents with comorbid major depressive disorder and an alcohol use disorder
      (AUD) who had previously participated in an acute phase study of open-label
      fluoxetine plus psychotherapy (Cornelius et al. 2001). The goal of this follow-up
      evaluation was to determine whether the decreases in drinking and in depressive
      symptoms that were noted during the acute phase study persisted at the follow-up
      evaluation. At the 1-year follow-up evaluation, the group continued to
      demonstrate significantly fewer depressive symptoms (according to the 24-item
      Hamilton Rating Scale for Depression) and a lower frequency of drinking (drinking
      days in the last 30 days) than they had demonstrated at the baseline of the acute
      phase study. Surprisingly, all of the subjects had chosen to discontinue their
      antidepressant medication by the second month of their naturalistic follow-up
      period. Three subjects had experienced a relapse of their major depression during
      the follow-up period, and three others demonstrated a persistence of their
      original depressive episode throughout the follow-up period. Also, the number of
      drinks per drinking day continued to be high (about five per day), which was not
      significantly different from the baseline level. Thus, the long-term therapeutic
      effects of an acute phase trial of fluoxetine plus psychotherapy were limited.
      The high rate of recurrence or persistence of major depression in our sample and
      in a previous sample of nonalcoholic adolescents with major depression (Emslie et
      al. 1998) and the significant levels of drinking of our comorbid adolescents
      suggest that longer term treatment may be needed for at least some adolescents
      with major depressive disorder and alcohol use disorder.

PMID- 15142390
TI  - Risperidone treatment of children with autistic disorder: effectiveness,
      tolerability, and pharmacokinetic implications.
AB  - BACKGROUND: Recent evidence indicates that atypical antipsychotics represent a
      promising option for the treatment of autistic disorder. In particular,
      risperidone appears to be effective in treating aggressiveness, hyperactivity,
      irritability, stereotypies, social withdrawal, and lack of interests. OBJECTIVE:
      The aim of the present study was to evaluate the effectiveness and tolerability
      of risperidone in children with autistic disorder and to examine the correlation
      between plasma levels of risperidone and its active metabolite 9
      hydroxyrisperidone (9-OH-risperidone) and the clinical response. METHODS: The
      effect of treatment with risperidone (0.75-2 mg/day; mean +/- SD dose = 1.26 +/-
      0.42 mg/day) was studied for 24 weeks in 20 children (14 boys, 6 girls) ages 3 to
      10 years (mean age 6.0 +/- 2.4 years), diagnosed with autistic disorder. Fourteen
      items selected from the Children's Psychiatric Rating Scale (CPRS-14) and
      Clinical Global Impression (CGI) were used for behavioral evaluation. Patients
      were classified as responders if they showed a 25% or greater decrease on CPRS-14
      total score at final evaluation compared with baseline and a final CGI rating of
      1 or 2. Patients were rated for extrapyramidal side effects on the Abnormal
      Involuntary Movement Scale (AIMS). Other side effects, including the expected
      side effects of atypical antipsychotics drugs, were assessed by a checklist.
      Blood samples for determination of risperidone and its active metabolite 9-OH
      risperidone were obtained after 12 weeks, and serum prolactin levels were
      measured on admission and at weeks 12 and 24. RESULTS: The psychopathological
      state, as assessed by CPRS, improved significantly over the duration of
      treatment. The mean CPRS-14 scores decreased significantly from 63.7 +/- 10.0 at
      baseline to 52.9 +/- 14.3 at week 12 (p < 0.01). At the end of 12 weeks of
      treatment, 8 patients were considered responders, and 10 patients reached a
      minimal improvement. No further improvement was observed in the following 12
      weeks. In all children, serum prolactin levels increased significantly (p <
      0.001) from 166 +/- 88 UI/mL at baseline to 504 +/- 207 UI/mL at week 12 of
      risperidone treatment. Weight gain and increased appetite were the most common
      unwanted effects. A mean increase of 3.7 +/- 1.7 kg in body weight was observed
      at final evaluation as compared with baseline. There was no significant
      correlation between percent improvement in total CPRS score and the plasma level
      of risperidone's active fractions (the sum of the risperidone and 9-OH
      risperidone plasma concentration). CONCLUSIONS: This study provides further
      evidence of the beneficial effects of risperidone in children diagnosed with
      autistic disorder. However, the potential advantages of risperidone should be
      weighed against the risk of unwanted effects, such as an increase in serum
      prolactin levels and weight gain. No relation was observed between total plasma
      risperidone and 9-OH-risperidone concentrations and clinical response.

PMID- 15142391
TI  - A naturalistic retrospective analysis of psychostimulants in pervasive
      developmental disorders.
AB  - OBJECTIVE: We set out to examine the effectiveness and tolerability of
      psychostimulants in children and adolescents with pervasive developmental
      disorders (PDDs). METHODS: Medical records of all patients with PDDs treated with
      a stimulant were retrospectively reviewed. Demographics, stimulant type, drug
      dosage, trial duration, and adverse effects were recorded. Global improvement,
      focused on symptoms of hyperactivity and inattention, was measured by the
      Clinical Global Impressions-Improvement scale, with positive response defined by
      a rating of much improved or very much improved. RESULTS: Of 195 patients (174
      males, 21 females; mean age +/- SD = 7.26 +/- 3.45 years, range 2-19 years), 61
      had more than one trial, resulting in a total of 274 separate stimulant trials.
      It was discovered that 24.6%, 23.2%, and 11.1% of patients with a history of one,
      two, or three stimulant trials, respectively, responded to their first stimulant
      trial. Among first trial nonresponders, 6 (14.0%) of 43 patients responded to a
      second trial. Of those who did not respond to their first or second stimulant
      trial, 2 (14.3%) of 14 patients responded to a third trial. Patients with
      Asperger's disorder, in contrast to those with autistic disorder or PDD not
      otherwise specified, were significantly more likely to respond to a stimulant
      trial (p < 0.01). Use of concomitant medication (p < 0.007) positively affected
      response, whereas no association was found between stimulant type and IQ and
      response. Adverse effects, including agitation, dysphoria, and irritability,
      often occurred (154 [57.5%] of 268 trials, with 6 missing values). CONCLUSIONS:
      Overall, stimulants appeared ineffective and poorly tolerated for the majority of
      patients with PDDs. Response may differ with PDD subtype. Controlled studies are
      needed to further evaluate these preliminary findings in a systematic manner.

PMID- 15142392
TI  - The off-label use of clozapine in adolescents with bipolar disorder, intermittent
      explosive disorder, or posttraumatic stress disorder.
AB  - OBJECTIVE: There are limited data in the literature regarding clozapine use in
      adolescents with diagnoses other than schizophrenia. This report describes the
      use of clozapine in adolescents with diagnoses of bipolar disorder, intermittent
      explosive disorder (IED), and posttraumatic stress disorder (PTSD). METHODS: A
      chart review of 39 adolescents treated with clozapine at two residential
      facilities was undertaken. Data extraction included demography, illness
      variables, medication information, and clinical outcomes. Categorical outcomes
      were analyzed using contingency statistics, and continuous variables were
      analyzed using a paired t test. RESULTS: The cohort included 26 females and 13
      males with a mean age of 14 years. Clozapine was titrated slowly, and the mean
      daily dose was 102 mg. The diagnoses included bipolar disorder (n = 7), IED (n =
      9), and PTSD (n = 19). There were significant reductions in polypharmacy once the
      clozapine dosage was stabilized. Prior to clozapine treatment, nearly 70% of the
      subjects were receiving either mood-stabilizing or antidepressant agents in
      combination with the previous antipsychotic drug. Once the clozapine dosage was
      stabilized, only 24% of the subjects required concomitant mood stabilizers (p <
      0.001), and only 21% of the subjects required concomitant antidepressants (p <
      0.001). Anxiolytic medication use was also significantly reduced during clozapine
      treatment. Most patients were discharged to a less restrictive setting. Eight
      subjects discontinued clozapine due to agranulocytosis (n = 1), neutropenia (n =
      2), excessive weight gain (n = 2), or not requiring it long term (n = 1), and
      data were unavailable in 2 subjects. Significant weight gain (5% or greater
      change from baseline) was noted in 20 subjects. CONCLUSIONS: Clozapine, in
      relatively modest doses, appears to have clinical benefits for adolescent with
      bipolar disorder, IED, and PTSD. There is no labeled indication for clozapine use
      in these disorders. Clozapine is also associated with serious side effects in
      subsets of individuals. Therefore, a very careful evaluation of the risk-to
      benefit ratio in each individual subject being considered for clozapine is highly
      recommended.

PMID- 15142393
TI  - A chart review of cyproheptadine for stimulant-induced weight loss.
AB  - Youths with attention deficit hyperactivity disorder often experience weight loss
      on stimulants, which may limit optimal dosing and compliance. Cyproheptadine has
      been shown in medical samples to stimulate weight gain. We conducted a
      retrospective chart review of 28 consecutive pediatric psychiatry outpatients
      prescribed cyproheptadine for weight loss or insomnia while on stimulants. Of
      these, 4 patients never took cyproheptadine consistently, and 3 discontinued it
      within the first 7 days due to intolerable side effects. Data were analyzed for
      21 other patients (age range 4-15 years) who continued with 4-8 mg of
      cyproheptadine nightly (mean final dose = 4.9 mg/day) for at least 14 days (mean
      duration = 104.7 days). Most had lost weight on stimulant alone (mean weight loss
      was 2.1 kg, mean weight velocity was -19.3 g/day). All 21 gained weight taking
      concomitant cyproheptadine, with a mean gain of 2.2 kg (paired t = 6.87, p <
      0.0001) and a mean weight velocity of 32.3 g/day. Eleven of 17 patients who had
      reported initial insomnia on stimulant alone noted significant improvements in
      sleep with cyproheptadine added. We conclude that concomitant cyproheptadine may
      be useful in youths with attention deficit hyperactivity disorder for stimulant
      induced weight loss, pending future randomized controlled trials.

PMID- 15142394
TI  - Atypical antipsychotic use in a state hospital inpatient adolescent population.
AB  - Atypical antipsychotics are now the most commonly prescribed antipsychotics in
      young patients. These drugs are increasingly being used because of better
      tolerance and safety as seen in the adult populations. Youth with more severe
      psychopathology who are treated in the inpatient setting have been overlooked in
      much of the published research, and the extent of use and rationale in this
      population is unknown. This naturalistic retrospective study examined a
      population of adolescents in an inpatient state hospital setting with regard to
      their use of atypical antipsychotics. All patients who received an inpatient
      prescription for atypical antipsychotics between January 1, 1997 and June 1, 2000
      and were ages 18 or younger at the time of medication initiation were included in
      the study. Twenty-three percent (88/380) of patients received an atypical
      antipsychotic: 68% (60/88) risperidone, 27% (24/88) olanzapine, and 5% (4/88)
      quetiapine. Psychotic disorders were considered as the primary diagnosis in only
      17% of patients treated with atypical antipsychotics, and no particular diagnosis
      was predictive of monotherapy with an atypical antipsychotic. In the adolescent
      populations, atypical antipsychotics are being used for a wide variety of
      diagnoses and are commonly used adjunctively (more than 80%) with many
      concomitant psychotropic medications. More research is needed to develop useful
      and specific practice guidelines in children and adolescents for these commonly
      used medications.

PMID- 15142395
TI  - Trends in psychotropic drug use in a child psychiatric hospital from 1991-1998.
AB  - OBJECTIVE: This study was undertaken to analyze inpatient prescribing patterns of
      psychotropic drugs in a child psychiatric hospital from 1991-1998. METHODS:
      Hospital pharmacy dispensing data were reviewed. Total admissions, first
      admissions, and readmissions were identified, and medication status of all
      patients at admission and at discharge was ascertained. Patterns of total
      psychotropic drug use and proportionate use of each drug class (antidepressants,
      mood stabilizers, antipsychotics stimulants, and alpha-2 antagonists) were
      evaluated. RESULTS: Controlling for the 2.3-fold rise in hospital admissions,
      there was a 73.0% increase in the use of psychotropic drugs from 1991-1998. The
      greatest relative increase was in the use of alpha-2 antagonists (from 3.3% to
      23.6%). Significant increases were also observed for antidepressants (from 35.6%
      to 77.3%), mood stabilizers (from 14.9% to 32.6%), and stimulants (from 10.5% to
      20.6%). Antipsychotic use showed no net change, although use of atypical agents
      largely supplanted that of conventional drugs. CONCLUSIONS: These findings
      document a marked and continuing increase in psychotropic drug use in child
      psychiatric inpatients during the 1990s. This trend occurred against a background
      of increased hospital admissions and shorter lengths of stay. Most of the
      increased use is accounted for by newer agents, even though data supporting their
      efficacy and safety in this population are limited.

PMID- 15142396
TI  - Psychotropic prescription practices in child psychiatric inpatients 9 years old
      and younger.
AB  - OBJECTIVE: We set out to examine psychotropic prescribing patterns among inner
      city children on public assistance admitted to a university-based inpatient
      service. METHODS: A chart review of children 9 years old and younger admitted
      between 1998 and 2001 recorded demographic variables, diagnoses, and admission
      and discharge medications. RESULTS: The sample (N = 301) was 78% male, 66%
      African American, and averaged 7.2 years of age. Of this sample, 85% had a
      behavior disorder on admission and discharge; 51.8% of the patients were
      medicated on admission, 78.7% on discharge. Approximately 25% received
      polypharmacy on either admission or discharge. Stimulants were the most widely
      used psychotropic (38.2% on admission, 60.5% on discharge). Other medications
      prescribed at admission versus discharge were alpha-2 agonists (9.3% vs. 9%),
      atypical antipsychotics (9% vs. 12%), antidepressants (8.3% vs. 15.9%), and mood
      stabilizers (5.6% vs. 2.3%). CONCLUSIONS: Among inner city children,
      pharmacotherapy is more prevalent in an inpatient unit compared with the
      community standard. Community physicians prescribed more mood stabilizers; the
      academic faculty used more stimulants, atypical antipsychotics, and
      antidepressants. Predictors of pharmacotherapy in the community such as age, sex,
      race, and a behavior disorder shifted at discharge to include only length of stay
      and a behavior disorder diagnosis. Further research is needed to clarify whether
      nonadherence, treatment failure, and social factors account for lower medication
      utilization in the community.

PMID- 15142397
TI  - Impairment in childhood anxiety disorders: preliminary examination of the child
      anxiety impact scale-parent version.
AB  - Although anxiety disorders are prevalent among children and adolescents, with a
      chronic and often disabling course, there is a paucity of research examining the
      specific ways in which anxiety interferes with various domains of functioning in
      childhood. The purpose of the current investigation was to examine the initial
      reliability and construct validity of the Child Anxiety Impact Scale-Parent
      version (CAIS-P). The CAIS-P is a parent-report measure consisting of School,
      Social, and Home/Family subscales. In a clinical sample (N = 92), the internal
      reliability and the convergent and divergent validity were evaluated. Internal
      consistency was good for the total score as well as each subscale (Cronbach's
      alpha ranged from 0.73-0.87). The CAIS-P total score demonstrated good construct
      validity, showing predicted significant correlations with the Child Behavior
      Checklist Internalizing Scale and the Child Depression Inventory but not the
      Externalizing Scale of the Child Behavior Checklist. The Social subscale of the
      CAIS-P was also significantly correlated with measures of social anxiety. The
      results provide initial support that the CAIS-P is a reliable and valid measure
      for the assessment of the impact of anxiety on child and adolescent functioning.

PMID- 15142398
TI  - Improved mood and behavior during treatment with a mineral-vitamin supplement: an
      open-label case series of children.
AB  - Several studies have demonstrated that psychiatric symptoms such as depression,
      mood swings, and aggression may be ameliorated by supplementation with broad
      based nutrient formulas containing vitamins, minerals, and sometimes essential
      fatty acids. These findings have been reported in young criminal offenders as
      well as in adults with mood disturbance and other psychiatric disorders. The
      purpose of the current case series was to explore the potential efficacy of a
      nutrient supplement in children. Children with mood and behavioral problems (N =
      11; 7 boys, 4 girls; 8-15 years old) participated; 9 completed this open-label
      trial. Parents completed the Child Behavior Checklist (CBCL), Youth Outcome
      Questionnaire (YOQ), and Young Mania Rating Scale (YMRS) at entry and following
      at least 8 weeks of treatment. Intent-to-treat analyses revealed decreases on the
      YOQ (p < 0.001) and the YMRS (p < 0.01) from baseline to final visit. For the 9
      completers, improvement was significant on seven of the eight CBCL scales, the
      YOQ, and the YMRS (p values from 0.05-0.001). Effect sizes for all outcome
      measures were relatively large. The findings suggest that formal clinical trials
      of broad nutritional supplementation are warranted in children with these
      psychiatric symptoms.

PMID- 15142399
TI  - Use of the "inverse neuroleptic" metoclopramide in Tourette syndrome: an open
      case series.
AB  - Neuroleptics are generally highly effective in suppressing tics, but their many
      adverse effects limit their usefulness. Animal studies have shown that, compared
      with both typical and atypical neuroleptics, metoclopramide has effects that are
      regionally circumscribed to rat motor striatum. Based on this observation and two
      prior case reports, metoclopramide was openly prescribed and individually
      titrated to diminish tics in 10 patients with Tourette syndrome. All patients
      improved on the Yale Global Tic Severity Scale by an average of 55%. Although we
      did not observe frank extrapyramidal symptoms, including tardive dyskinesia,
      these data are not sufficient to support clinical recommendations because of many
      limitations, including the absence of systematic ratings of nontic abnormal
      movements. However, controlled clinical studies and additional basic
      investigations of metoclopramide are warranted.

PMID- 15142400
TI  - Atomoxetine and stimulants in combination for treatment of attention deficit
      hyperactivity disorder: four case reports.
AB  - Atomoxetine and stimulants have both been demonstrated effective as single agents
      for treatment of attention deficit hyperactivity disorder in children,
      adolescents, and adults. However, attention deficit hyperactivity disorder
      symptoms in some patients do not respond adequately to single-agent treatment
      with these medications, each of which is presumed to impact dopaminergic and
      noradrenergic networks by alternative mechanisms in different ratios. Four cases
      are presented to illustrate how atomoxetine and stimulants can be utilized
      effectively in combination to extend duration of symptom relief without
      intolerable side effects or to alleviate a wider range of impairing symptoms than
      either agent alone. This combined pharmacotherapy appears effective for some
      patients who do not respond adequately to monotherapy, but because there is
      virtually no research to establish safety and effectiveness of such strategies,
      careful monitoring is needed.

PMID- 15142401
TI  - Ziprasidone treatment of two adolescents with psychosis.
AB  - Ziprasidone is an atypical antipsychotic that is approved for the treatment of
      adults with schizophrenia. To date, only a limited number of studies have been
      published on the use of ziprasidone for treating neuropsychiatric conditions in
      children and adolescents. This report describes ziprasidone treatment of two
      adolescents with severe psychotic illness who had unsuccessful trials of
      alternative antipsychotic medications. These patients presented with
      hallucinations and grossly disorganized speech and behavior. Further study is
      needed to determine if these findings can be generalized.

PMID- 15142402
TI  - Selective serotonin reuptake inhibitor-related extrapyramidal symptoms in
      autistic children: a case series.
AB  - Abnormal movements occur rarely with selective serotonin reuptake inhibitors
      (SSRIs). This report describes four consecutive autistic children who developed
      extrapyramidal side effects (EPS) following SSRI exposure. Videotapes, physician
      notes, and parental interviews were used retrospectively to rate symptoms on the
      Extrapyramidal Symptom Rating Scale. Findings suggest that EPS is a potential
      complication of SSRI treatment in autistic children.

PMID- 15142403
TI  - Tardive dystonia induced by atypical neuroleptics: a case report with olanzapine.
AB  - We report the case of a 17-year-old-boy with schizophrenia who developed tardive
      dystonia after 9 months of treatment with olanzapine. This case and the relevant
      literature show that when neuroleptic treatment is indicated, switching to
      another atypical neuroleptic might be helpful for both tardive dystonia and
      schizophrenia. In such a case, clozapine appears to be the first-line therapeutic
      option.

PMID- 15142404
TI  - Successful treatment of trichotillomania with olanzapine augmentation in an
      adolescent.

PMID- 15142405
TI  - Risperidone-induced obsessive-compulsive symptoms in two children.

PMID- 15142406
TI  - Bupropion insufflation in a teenager.

PMID- 15142407
TI  - Multi-modality imaging identifies key times for annexin V imaging as an early
      predictor of therapeutic outcome.
AB  - Radiolabeled annexin V may provide an early indication of the success or failure
      of anticancer therapy on a patient-by-patient basis as an in vivo marker of tumor
      cell killing. An important question that remains is when, after initiation of
      treatment, should annexin V imaging be performed. To address this issue, we
      obtained simultaneous in vivo measurements of tumor burden and uptake of
      radiolabeled annexin V in the syngeneic orthotopic murine BCL1 lymphoma model
      using in vivo bioluminescence imaging (BLI) and small animal single-photon
      emission computed tomography (SPECT). BCL1 cells labeled for fluorescence and
      bioluminescence assays (BCL1-gfp/luc) were injected into mice at a dose that
      leads to progressive disease within two to three weeks. Tumor response was
      followed by BLI and SPECT before and after treatment with a single dose of 10
      mg/kg doxorubicin. Biodistribution analyses revealed a biphasic increase of
      annexin V uptake within the tumor-bearing tissues of mice. An early peak
      occurring before actual tumor cells loss was observed between 1 and 5 hr after
      treatment, and a second longer sustained rise from 9 to 24 hr after therapy,
      which heralds the onset of tumor cell loss as confirmed by BLI. Multimodality
      imaging revealed the temporal patterns of tumor cell loss and annexin V uptake
      revealing a better understanding of the timing of radiolabeled annexin V uptake
      for its development as a marker of therapeutic efficacy.

PMID- 15142408
TI  - Quantitative comparison of the sensitivity of detection of fluorescent and
      bioluminescent reporters in animal models.
AB  - Bioluminescent and fluorescent reporters are finding increased use in optical
      molecular imaging in small animals. In the work presented here, issues related to
      the sensitivity of in vivo detection are examined for standard reporters. A high
      sensitivity imaging system that can detect steady-state emission from both
      bioluminescent and fluorescent reporters is described. The instrument is
      absolutely calibrated so that animal images can be analyzed in physical units of
      radiance allowing more quantitative comparisons to be performed. Background
      emission from mouse tissue, called autoluminescence and autofluorescence, is
      measured and found to be an important limitation to detection sensitivity of
      reporters. Measurements of dual-labeled (bioluminescent/fluorescent) reporter
      systems, including PC-3M-luc/DsRed2-1 and HeLa-luc/PKH26, are shown. The results
      indicate that although fluorescent signals are generally brighter than
      bioluminescent signals, the very low autoluminescent levels usually results in
      superior signal to background ratios for bioluminescent imaging, particularly
      compared with fluorescent imaging in the green to red part of the spectrum.
      Fluorescence detection sensitivity improves in the far-red to near-infrared,
      provided the animals are fed a low-chlorophyll diet to reduce autofluorescence in
      the intestinal region. The use of blue-shifted excitation filters is explored as
      a method to subtract out tissue autofluorescence and improve the sensitivity of
      fluorescent imaging.

PMID- 15142409
TI  - Comparison of transfection agents in forming complexes with ferumoxides, cell
      labeling efficiency, and cellular viability.
AB  - By complexing ferumoxides or superparamagnetic iron oxide (SPIO) to transfection
      agents (TAs), it is possible to magnetically label mammalian cells. There has
      been no systematic study comparing TAs complexed to SPIO as far as cell labeling
      efficiency and viability. This study investigates the toxicity and labeling
      efficiency at various doses of FEs complexed to different TAs in mammalian cells.
      Different classes of TAs were used, such as polycationic amines, dendrimers, and
      lipid-based agents. Cellular toxicity was measured using doses of TAs from 1 to
      50 microg/mL in incubation media. Iron incorporation efficiency was measured by
      combining various amounts of FEs and different doses of TAs. Lipofectamine2000
      showed toxicity at lowest dose (1 microg/mL), whereas FuGENE6 and low molecular
      weight poly-L-lysine (PLL) showed the least toxicity. SPIO labeling efficiency
      was similar with high-molecular-weight PLL (388.1 kDa) and superfect, whereas
      FuGENE6 and low-molecular-weight PLL were inefficient in labeling cells.
      Concentrations of 25 to 50 microg/mL of FEs complexed to TAs in media resulted in
      sufficient endocytosis of the SPIO into endosomes to detect cells on cellular
      magnetic resonance imaging.

PMID- 15142410
TI  - Visualization of the dynamics of gene expression in the living mouse.
AB  - Reporter genes can monitor the status and activity of recombinant genomes in a
      diverse array of organisms, from bacteria and yeast to plants and animals. We
      have combined luciferase reporter genes with a conditional gene expression system
      based on regulatory elements from the lac operon of Escherichia coli to visualize
      the dynamics of gene expression in realtime in the living mouse. Using this
      technology, we have determined the rate of gene induction and repression, the
      level of target gene activity in response to different doses of inducer, and the
      schedule of induction during early embryogenesis of both the endogenous and the
      experimentally manipulated programs of mammalian gene expression associated with
      the HD/Hdh locus. The combination of in vivo imaging and lac regulation is a
      powerful tool for generating conditional transgenic mice that can be screened
      rapidly for optimal regulation and expression patterns, and for monitoring the
      induction and repression of regulated genes noninvasively in the living animal.

PMID- 15142411
TI  - Characterization of coelenterazine analogs for measurements of Renilla luciferase
      activity in live cells and living animals.
AB  - In vivo imaging of bioluminescent reporters relies on expression of light
      emitting enzymes, luciferases, and delivery of chemical substrates to expressing
      cells. Coelenterazine (CLZN) is the substrate for a group of bioluminescent
      enzymes obtained from marine organisms. At present, there are more than 10
      commercially available CLZN analogs. To determine which analog is most suitable
      for activity measurements in live cells and living animals, we characterized 10
      CLZN analogs using Renilla luciferase (Rluc) as the reporter enzyme. For each
      analog, we monitored enzyme activity, auto-oxidation, and efficiency of cellular
      uptake. All CLZN analogs tested showed higher auto-oxidation signals in serum
      than was observed in phosphate buffer or medium, mainly as a result of auto
      oxidation by binding to albumin. CLZN-f, -h, and -e analogs showed 4- to 8-fold
      greater Rluc activity, relative to CLZN-native, in cells expressing the enzyme
      from a stable integrant. In studies using living mice expressing Rluc in
      hepatocytes, administration of CLZN-e and -native produced the highest signal.
      Furthermore, distinct temporal differences in signal for each analog were
      revealed following intravenous or intraperitoneal delivery. We conclude that the
      CLZN analogs that are presently available vary with respect to hRluc utilization
      in culture and in vivo, and that the effective use of CLZN-utilizing enzymes in
      living animals depends on the selection of an appropriate substrate.

PMID- 15142412
TI  - In vivo respiratory-gated micro-CT imaging in small-animal oncology models.
AB  - Micro-computed tomography(micro-CT) is becoming an accepted research tool for the
      noninvasive examination of laboratory animals such as mice and rats, but to date,
      in vivo scanning has largely been limited to the evaluation of skeletal tissues.
      We use a commercially available micro-CT device to perform respiratory gated in
      vivo acquisitions suitable for thoracic imaging. The instrument is described,
      along with the scan protocol and animal preparation techniques. Preliminary
      results confirm that lung tumors as small as 1 mm in diameter are visible in vivo
      with these methods. Radiation dose was evaluated using several approaches, and
      was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging
      protocol. The combination of high-resolution CT imaging and respiratory-gated
      acquisitions appears well-suited to serial in vivo scanning.

PMID- 15142416
TI  - Surviving sepsis.

PMID- 15142413
TI  - Bioluminescence detection of cells having stabilized p53 in response to a
      genotoxic event.
AB  - Inactivation of p53 is one of the most frequent molecular events in neoplastic
      transformation. Approximately 60% of all human tumors have mutations in both p53
      alleles. Wild-type p53 activity is regulated in large part by the proteosome
      dependent degradation of p53, resulting in a short p53 half-life in unstressed
      and untransformed cells. Activation of p53 by a variety of stimuli, including DNA
      damage induced by genotoxic drugs or radiation, is accomplished by stabilization
      of wild-type p53. The stabilized and active p53 can result in either cell-cycle
      arrest or apoptosis. Surprisingly, the majority of tumor-associated, inactivating
      p53 mutations also result in p53 accumulation. Thus, constitutive elevation of
      p53 levels in cells is a reliable measure of p53 inactivation, whereas
      transiently increased p53 levels reflect a recent genotoxic stress. In order to
      facilitate noninvasive imaging of p53 accumulation, we here describe the
      construction of a p53-luciferase fusion protein. Induction of DNA damage in cells
      expressing the fusion protein resulted in a time-dependent accumulation of the
      fusion that was noninvasively detected using bioluminescence imaging and
      validated by Western blot analysis. The p53-Luc protein retains p53 function
      because its expression in HCT116 cells lacking functional p53 resulted in
      activation of p21 expression as well as induction of apoptosis in response to a
      DNA damaging event. Employed in a transgenic animal model, the proposed p53
      reporter fusion protein will be useful for studying p53 activation in response to
      exposure to DNA-damaging carcinogenic agents. It could also be used to study p53
      stabilization as a result of inactivating p53 mutations. Such studies will
      further our understanding of p53's role as the "guardian of the genome" and its
      function in tumorigenesis.

PMID- 15142417
TI  - The challenge of improving therapy of surgical intensive care patients.

PMID- 15142418
TI  - Signal transduction pathway in endothelial dysfunction.
AB  - BACKGROUND: Endothelial dysfunction is an important feature of sepsis, acute
      respiratory distress syndrome (ARDS), and other infectious conditions.
      Previously, we reported an in vitro model to study endothelial dysfunction, in
      which endothelial cells are induced to form capillary tube networks by culturing
      on a basement membrane matrix (Matrigel). In this study, we defined the signal
      transduction pathways that lead to endothelial cell function and capillary
      disruption characteristic of sepsis and other infectious conditions. METHODS:
      Human aortic endothelial cells (HAEC) were cultured on a laminin-rich matrix to
      form capillary-like networks. The HAECs were treated with a protein tyrosine
      phosphatase inhibitor (sodium orthovanadate), a phosphoinositon-3-phosphate
      inhibitor (wortmannin), or a protein kinase C inhibitor (bisindolylmaleimide)
      before capillary tubes had formed or after the capillary tubes had matured. The
      degree of capillary tube formation was quantified by counting the intersection of
      capillary networks in triplicate wells. Statistical significance was determined
      by analysis of variance. RESULTS: Endothelial dysfunction occurred after
      inhibition of protein tyrosine phosphatase or protein kinase C. Whereas
      inhibition of phosphoinositon-3-phosphate did not cause endothelial dysfunction,
      sodium orthovanadate (2-20 microM) and bisindolylmaleimide (2-10 microM)
      significantly reduced capillary networks. The mean +/- SD of the number of
      capillary tubes in the control, sodium orthovanadate-treated, and
      bisindolylmaleimide-treated groups were 251.0 +/- 7.0, 65.6 +/- 9.9 (p < 0.001),
      and 181.7 +/- 0.1 (p < 0.001), respectively. Sodium orthovanadate (20-200 microM)
      and bisindolylmaleimide (10-100 microM) inhibited capillary tube formation. At
      higher concentrations, sodium orthovanadate (> 200 microM) and
      bisindolylmaleimide (>100 microM) disrupted mature capillary tubes. CONCLUSIONS:
      Our results suggest that PKC and protein tyrosine phosphatase play a role in
      endothelial dysfunction by interfering with the phosphorylation signals within
      endothelial cells. These mechanisms may be important in the endothelial
      dysfunction in sepsis and other infectious conditions.

PMID- 15142419
TI  - Bedside laparotomy for trauma: are there risks?
AB  - BACKGROUND: Critically ill trauma patients are often too unstable for safe
      transfer to the operating room. Damage control laparotomy patients frequently
      require early reoperation and have a reported mortality of 50-60%. As a result,
      many of these patients must undergo laparotomy in the intensive care unit. We
      hypothesized that patients undergoing bedside laparotomy (BSL) and managed with
      the abdomen left open would have an unacceptably high mortality or intra
      abdominal complications. METHODS: We performed a retrospective chart review of
      our Trauma Registry. Of the 11,096 consecutive trauma admissions from March 1,
      1996 to May 20, 2000, 75 patients underwent 95 BSL. Patients were stratified
      according to injury severity score (ISS), base deficit (BD), lactic acid (LA),
      total transfusion (TRBC) requirements, indication for BSL, mechanism of injury,
      infectious complications (intra-abdominal abscess (IAA), fistula), and length of
      hospital stay. RESULTS: Seventy-five patients underwent 95 BSL. Mean ISS was 50.6
      +/- 18.9, mean BD was -11.9 (+/- 5), and the mean LA was 5 +/- 5 for the study
      group. The TRBC for the group was 43.7 +/- 42.6 units. Indications for the 95 BSL
      were (1) abdominal compartment syndrome (n = 47, 49.5%); (2) suspected intra
      abdominal infection (n = 18, 19.0%); (3) washout/pack removal (n = 14, 14.7%);
      (4) washout with fascial closure (n = 12, 12.6%); and (5) other (n = 4, 4.2%).
      Twenty-nine of 75 patients (39.2%; ISS 52.3 +/- 18.8) died within 72 h of
      operation. Of the 46 remaining patients, an additional eight died 72 h or more
      after operation, for a late mortality rate of 17.4% and a total mortality rate of
      49%. None of these deaths were attributable to either the operation or to post
      operative IAA or fistula formation; all late deaths were secondary to multiple
      organ failure. Intra-abdominal abscesses developed in three of 46 patients
      (6.5%), each of whom had a TRBC of >100 units (mean, 160 units). Five of 46
      patients (10.9%) developed enterocutaneous fistulae. None of these eight patients
      died. Thirty-eight of 75 patients (50.7%) survived to discharge, with a mean ISS
      of 40 (+/- 11.9). CONCLUSIONS: Despite the high acuity of the population
      undergoing BSL, 50.7% of patients survived. Moreover, during BSL, IAA and fistula
      formation occurred at low rates.

PMID- 15142420
TI  - Nosocomial infections adversely affect the outcomes of patients with serious
      intraabdominal infections.
AB  - BACKGROUND: Patients with serious intraabdominal infections (IAI) who
      subsequently acquire nosocomial infections (NI) have been shown to have adverse
      outcomes. We evaluated factors that put patients at risk for developing NI and
      examined the effect of the NI on outcomes. METHODS: This study was a
      retrospective review of NI among 168 patients diagnosed with IAI over a seven
      year period. RESULTS: Sixty-six patients (39.3%) developed 98 NI (23 urinary
      tract, 20 surgical site, 19 pneumonia, 14 bloodstream, 12 recurrent peritonitis,
      seven intravascular catheter-related, and three enteric). There were 35 males and
      31 females. Patients with NI were older (56.0 +/- 18.3 vs. 47.0 +/- 15.6 years, p
      = 0.001), had a higher admission APACHE II score (10.7 +/- 6.1 vs. 7.5 +/- 5.1
      points, p = 0.001), and more often had concomitant medical diagnoses (27.3% vs.
      12.7%, OR = 2.57, 95% CI: 1.159-5.69, p = 0.018) than those who did not develop
      infection. Antimicrobial resistance among the IAI was higher in the NI group
      (19.7 vs. 5.9%, OR = 3.93, 95% CI: 1.41-10.93, p = 0.006). Patients who developed
      NI had an increased mortality rate (27.0% vs. 4.0%, OR = 8.87, 95% CI: 2.82
      27.86, p < or = 0.0001), longer hospital stay (24.7 +/- 19.5 vs. 11.7 +/- 8.1
      days, p < or = 0.0001), required more days of intravenous antibiotics (11.5 +/-
      8.0 vs. 7.6 +/- 4.4 days, p < or = 0.0001), and were more likely to be admitted
      to an intensive care unit (54.5% vs. 25.5%, OR = 3.51, 95% CI: 1.82-6.77, p < or
      = 0.0001). Multivariate analysis demonstrated that antimicrobial resistance and
      an APACHE II score of > or = 10 independently predicted the development of a
      nosocomial infection. Age >/= 50 years, APACHE II score > or = 10, or the
      presence of a NI independently predicted death. CONCLUSIONS: The development of
      NI following treatment of an IAI significantly affects mortality, hospital length
      of stay, and treatment. Early recognition and treatment of these infections,
      combined with strategies to prevent NI, may be important to improve outcomes in
      this patient population.

PMID- 15142422
TI  - The relationships of hypocholesterolemia to cytokine concentrations and mortality
      in critically ill patients with systemic inflammatory response syndrome.
AB  - BACKGROUND: Decreased concentrations of total cholesterol, lipoproteins, and
      lipoprotein cholesterols occur early in the course of critical illness. Low
      cholesterol concentrations correlate with high concentrations of cytokines such
      as interleukin (IL)-6 and IL-10, and may be due to decreased synthesis or
      increased catabolism of cholesterol. Low cholesterol concentrations have been
      associated clinically with several adverse outcomes, including the development of
      nosocomial infections. The study was performed to test the hypothesis that a low
      cholesterol concentration predicts mortality and secondarily predicts the
      development of organ dysfunction in critical surgical illness. METHODS: A
      prospective study was undertaken of 215 patients admitted to a university
      surgical ICU with systemic inflammatory response syndrome (SIRS). Serial blood
      samples were collected within 24 h of admission, as well as on the morning of
      days 2, 4, and 7 of the ICU stay for as long as the patients were in the ICU.
      Demographic data and predetermined outcomes were noted. RESULTS: One hundred nine
      patients had at least two samples drawn and form the population for analysis.
      Sixty-two of the patients had three samples obtained, whereas 42 patients had
      four samples obtained. By univariate analysis, non-survivors were more severely
      ill on admission (APACHE III), more likely to have been admitted to the ICU as an
      emergency, more likely to develop a nosocomial infection, and more likely to
      develop severe organ dysfunction (MODS) (all, p < 0.05). Death was associated on
      day 1 with increased concentrations of sIL2R, IL-6, IL-10, and sTNFR-p75 (all, p
      < 0.01), but there were initially no differences in serum lipid concentrations.
      However, by day 2, concentrations of IL-6, IL-10, and cholesterol had decreased
      significantly (all, p < 0.05) from day 1 in non-survivors but not in survivors;
      the difference in serum cholesterol concentration persisted to day 7 (p < 0.05).
      Persistently elevated concentrations of IL-6 and IL-10 were observed in patients
      who developed severe MODS. By logistic regression, increased APACHE III score,
      development of a nosocomial infection, and decreased cholesterol concentration
      were independently associated with mortality. CONCLUSIONS: Decreased serum
      cholesterol concentration is an independent predictor of mortality in critically
      ill surgical patients. Repletion of serum lipids is a feasible therapeutic
      approach for the management of critical illness.

PMID- 15142421
TI  - Inhibition of cyclooxygenase-2 by NS-398 following hemorrhage and subsequent
      sepsis: no beneficial effects in either gender.
AB  - BACKGROUND: Inhibition of cyclooxygenase-2 with a reduction of prostaglandin
      E(2)production by the specific antagonist NS-398 has been shown to have
      beneficial effects on immune function and survival in a trauma model. Immune
      function after experimental hemorrhagic shock and subsequent sepsis may be gender
      related, with enhanced immunity and better survival in females. However, it
      remains unclear if the observed effect of NS-398 treatment is gender-related
      following hemorrhagic shock and subsequent sepsis. METHODS: Male and female CBA/J
      mice (age: 2-3 months) were subjected to hemorrhagic shock (35 +/- 5 mm Hg for 90
      min and fluid resuscitation) or sham operation. At resuscitation and after 20 and
      40 h each received either NS-398 10 mg/kg or placebo i.p. At 48 h after
      resuscitation, either splenocytes and peritoneal macrophages (pM phi) were
      harvested (n = 8 per group), or polymicrobial sepsis was induced by cecal
      ligation and puncture (CLP). Following CLP, either 10-day survival (n = 15 per
      group) was determined or pM phi and splenocytes were harvested 4 h after CLP (n =
      8 per group). Cytokine release of pM phi, and splenocyte proliferation and
      responsiveness in vitro were assessed. RESULTS: Treatment with NS-398 led to
      lower PGE(2) levels as compared to placebo-treated animals, reaching significance
      (p < 0.05) in males. Placebo-treated males had significantly depressed
      proinflammatory immune response (IL-1, IL-6, IL-2, IFN-gamma) after hemorrhagic
      shock and experienced further suppression by CLP (all, p < 0.05). In contrast,
      young females displayed unchanged cytokine release after hemorrhagic shock, but a
      comparable suppression following CLP. Treatment with NS-398 did not influence
      cytokine release nor survival. CONCLUSIONS: Despite a significant reduction of
      PGE(2) concentration, NS-398 treatment has no beneficial effects on cytokine
      release and survival in this model of hemorrhage and subsequent sepsis.

PMID- 15142423
TI  - Female sex hormones protect red blood cells from damage after trauma-hemorrhagic
      shock.
AB  - BACKGROUND: Trauma/hemorrhagic shock (T/HS) is known to cause changes in red
      blood cell (RBC) deformability and resting shape. Our previous studies have shown
      that proestrus female rats are more protected from shock-induced RBC damage than
      diestrus females or males. However, it is unclear whether female or male sex
      hormones can influence the severity of these alterations. METHODS: Red blood cell
      deformability and shape were examined in proestrus female rats, and
      oophorectomized female rats, as well as in castrated and non-castrated male rats
      (5-10 animals per group) subjected to T/HS. Red blood cell deformability was
      measured by laser ektacytometry whereas erythrocyte shape was evaluated by
      scanning electron microscopy. RESULTS: Proestrus female rats subjected to T/HS
      did not show either significant RBC deformability changes (decrease in elongation
      index) or shape alterations (increase in the percentage of reversibly and
      irreversibly changed cells). Oophorectomized rats demonstrated more severe RBC
      changes than did non-oophorectomized rats. The degree of RBC damage was the same
      in castrated and non-castrated males, which was significantly worse than in
      proestrus females. CONCLUSIONS: Removal of female sex hormones increases the
      severity of T/HS-induced RBC changes, indicating that female sex hormones protect
      against RBC damage. In contrast, male sex hormones do not appear to modulate T/HS
      RBC dysfunction.

PMID- 15142424
TI  - LPS tolerance in septic ICU patients: laboratory and technical considerations.

PMID- 15142427
TI  - The horizons of medicine.

PMID- 15142425
TI  - Philip S. Barrie, M.D., M.B.A. Interview by Vicki Glaser.

PMID- 15142429
TI  - Gerontology Research Group.

PMID- 15142430
TI  - Pieces of the puzzle. An interview with Michael Fossel, M.D., PH.D. by Vicki
      Glaser.

PMID- 15142431
TI  - Telomeres shorten with age in rat cerebellum and cortex in vivo.
AB  - Normal somatic cells have a finite replicative capacity. With each cell division,
      telomeres, the ends of linear chromosomes, progressively shorten until they reach
      a critical length, at which point the cells enter replicative senescence. Some
      cells maintain their telomeres by the action of the telomerase enzyme. Glia,
      particularly microglia, are the only adult cell type in the central nervous
      system (CNS) that exhibit a significant mitotic potential, and are thus
      susceptible to telomere shortening. Previous research in our laboratory has found
      that telomeres shorten in rat microglia with increasing time in vitro. Our
      current hypothesis is that telomeres shorten in rat brain in vivo with increasing
      age. Tissue samples of cerebellum and cortex were obtained from Sprague-Dawley
      rats of various ages. Genomic DNA and total protein was isolated from each sample
      for telomere length measurement via Southern blot analysis (up to 5 months) and
      telomerase activity measurement via TRAP analysis (up to 6 months), respectively.
      Telomere shortening occurs in vivo in both rat cerebellum and cortex from day 21
      to approximately 5 months of age. Cortex samples possessed shorter telomeres than
      did cerebellum samples. The longest telomeres undergo the most dramatic
      shortening, while the shortest telomeres exhibit only slight attrition.
      Telomerase activity slowly increases from day 21 to approximately 6 months of
      age, with the cerebellum exhibiting higher activity than cortex in all instances.
      These results indicate that telomere shortening occurs in rat brain in vivo with
      increasing age, and that the low levels of telomerase activity present may be
      preferentially recruited to maintain the shortest telomeres while allowing the
      longer ones to shorten more rapidly. Since microglia are thought to be the only
      mature cells of the postnatal CNS undergoing appreciable cell division, we
      propose that the telomere shortening occurring in the adult rat brain with age
      can be largely attributed to microglial cell division. Our findings provide an
      impetus to further investigate the pattern of telomere length and telomerase
      activity that emerges with further aging in the rat brain.

PMID- 15142432
TI  - Will human life expectancy quadruple in the next hundred years? Sixty
      gerontologists say public debate on life extension is necessary.
AB  - Sixty gerontologists were asked for estimates regarding the development of future
      life expectancy. For a person born in the year 2100, life expectancy estimates
      had a median of 100 years and a mean of 292 years. Changes in biogerontology
      suggest that the search for the "fountain of youth" is gaining respectability,
      becoming competitive with compression of morbidity as the predominant scientific
      goal. Appropriate debate should address questions raised by such a goal and
      prepare for sudden advances that may have a large impact on society.

PMID- 15142433
TI  - Telomerase, telomerase inhibition, and cancer.
AB  - Telomeres, located at the ends of eukaryotic chromosomes, are synthesized by the
      enzyme telomerase and are responsible for maintaining chromosome length. The
      absence of telomerase in most somatic cells has been associated with telomere
      shortening and aging of these cells. In contrast, high levels of telomerase
      activity are observed in over 90% of human cancer cells. The absence of
      telomerase in normal and aging cells is considered a natural defense against
      development of cancer. However, we do not know what triggers the reappearance of
      telomerase in cancer cells. Telomerase activity is directly correlated with the
      expression of its active catalytic component, the human telomerase reverse
      transcriptase (hTERT), which is believed to be controlled primarily at the level
      of transcription. Elucidation of the control of telomerase in aging and in cancer
      as an age-related disease has considerable potential in leading to novel
      approaches in anti-aging medicine.

PMID- 15142435
TI  - Soy-induced brain atrophy?
AB  - Epidemiological research has demonstrated a positive correlation between tofu
      consumption and brain atrophy in men. Because correlation does not prove
      causation, correlation-based hypotheses should be tested against the availability
      of possible causal mechanisms. While it has been shown that the soy phytoestrogen
      genistein inhibits neuroprotective functions in cell cultures, recent in-vivo
      findings strengthen the case for a possible causal mechanism of soy-induced
      neurodegeneration. The author suggests possible responses to this data regarding
      soy consumption.

PMID- 15142434
TI  - Reduced level of serum thiols in patients with a diagnosis of active disease.
AB  - Oxidative stress, or the production of oxygen-centered free radicals, has been
      hypothesized as the major source of DNA damage that in turn can lead to altered
      genetic expression, disease, and aging of humans. Serum protein thiol levels in
      blood are a direct measure of the in vivo reduction/oxidation (redox) status in
      humans, because thiols react readily with oxygen-containing free radicals to form
      disulfides. Moreover, serum thiols also reflect DNA repair capacity and the
      possible eventual accumulation of genetic damage, since a key DNA repair enzyme,
      poly ADP-ribose polymerase (PARP), is thiol/disulfide redox regulated. This study
      tests the hypothesis that serum protein thiols can be used to estimate individual
      aging status by comparing the levels of apparently healthy subjects (n = 90) to
      those of individuals (n = 306) with an active disease diagnosis. Nine categories
      of human disorders all showed highly significant reductions in serum protein
      thiols from 46 to 91 nM cysteine/200 microL serum (mean +/- S.D. = 59 +/- 40)
      compared to a control mean of 128 +/- 39 nM cysteine/200 microL serum (p <.001).
      These data strongly confirm an important role of oxidative stress in human
      disease development, and identify serum thiol status as a potential biochemical
      endpoint useful in the assessment of aging.

PMID- 15142437
TI  - Table of world-wide living supercentenarians.

PMID- 15142439
TI  - [Cardiac hemodynamics after suprarenal ligation of the inferior vena cava and the
      resection of the right kidney or injection of ligustrazine in rats].
AB  - BACKGROUND & OBJECTIVE: Primary retroperitioneal tumor often invades large
      vessels; the difficulty of operation is the management of the vessels, especially
      the inferior vena cava (IVC). The suprarenal ligation of the IVC was considered
      to be dangerous. The aim of this study was to investigate the cardiac
      hemodynamics following suprarenal ligation of the IVC and the resection of the
      right kidney or injection of ligustrazine in rats, and to provide theories and
      guides for the clinical operations. METHODS: The rats were divided into six
      groups of seven. The groups were control group, false operation group, suprarenal
      ligation of the IVC group, suprarenal ligation of IVC and resection of right
      kidney group, ligustrazine group, and placebo group. All rats were determined for
      heart rate, ejection fraction, cardiac output, stroke volume, arterial pressure
      at 1st, 6th, 24th, 48th hour after the operations. RESULTS: The indexes of the
      false operation group had no change. CO(0.018+/-0.002 L/min), SV(0.054+/-0.008
      ml), AP(H)(173+/-12 mmHg), AP(L)(161+/-11 mmHg) decreased to the lowest point at
      1st hour following the suprarenal ligation of the IVC, but compensated completely
      at 48th hour after the operation. All rats in this group survived during the
      study period. CO(0.012+/-0.002 L/min), SV(0.038+/-0.005 ml), AP(H)(138+/-8 mmHg),
      AP(L)(131+/-9 mmHg)decreased to the lowest point at 1st hour following the
      suprarenal ligation of the IVC and resection of the right kidney, CO and SV were
      not compensated completely at 48th hour after the operation, two rats died in
      this group. CO (0.025+/-0.004 L/min), SV(0.063+/-0.009 ml), AP(H)(190+/-14 mmHg),
      AP(L)(163+/-9 mmHg)decreased to the lowest point at 1st hour following the
      suprarenal ligation of the IVC, but compensated quickly at 24th hour after the
      operation, all rats survived in this group. The placebo group, compared with the
      ligustrazine group, had no obvious change. CONCLUSION: Cardiac function was
      affected by low returned blood volume following the suprarenal ligation of the
      IVC, but compensated completely at 48th hour after the operation. The suprarenal
      ligation of the IVC and injection of ligustrazine could improve cardiac function
      of the experimental rats. The suprarenal ligation of the IVC and resection of the
      right kidney, which not only increased the operative difficulty but also reduced
      cardiac functional compensation and appeared the death of rats, were not
      appropriate. We suggest to ligate the suprarenal IVC and to inject ligustrazine
      after resecting the tumor and infiltrated IVC, not to resect normal right kidney.
      To infuse solution by upper limb to increase returned blood volume in early phase
      after the operation.

PMID- 15142440
TI  - [Effect of papillary thyroid carcinoma related gene PTC1 on subcellular
      localization and function of ATM cell].
AB  - BACKGROUND & OBJECTIVE: Papillary thyroid carcinoma is characterized by RET
      (rearranged during transfection)/PTC (papillary thyroid carcinoma)
      rearrangements. However, the function of RET/PTC in carcino- genesis is not well
      understood. This study was designed to investigate the interaction between DNA
      double-strand break sensor ATM (mutated in ataxia telangiectasia) kinase and
      PTC1, a rearranged form of proto-oncogene ret, to explore the role of ret
      rearrangements in carcinogenesis. METHODS: RET TK phosphorylation was determined
      by in vitro kinase assay using the immunoprecipitation with anti-ATM antibody as
      kinase and the immunoprecipitation of HA-tagged TK as substrate. The location of
      ATM-LZPR in COS7 cells coexpressed with PTC1 was investigated by protein extracts
      of cytoplasm and nucleus. The phosphorylation level of p53, was determined by
      Western blot analysis with the antibody against phosphorylated p53, and the cell
      cycle was determined by flow cytometry when PTC1 overexpressed. RESULTS: ATM
      directly phosphorylated TK domain of PTC1 in vitro kinase assay. ATM-LZPR was
      located in both cell cytoplasm and nucleus when PTC1 was not expressed, however,
      co-overexpression of PTC1 and ATM-LZPR made the latter locate only in the
      cytoplasm. In addition, overexpression of PTC1 inhibited the phosphorylation
      level of p53 by ATM and caused G(1)/S phase arrest of cell cycle. CONCLUSIONS:
      PTC1 may remain ATM kinase in cytoplasm and inhibit the phosphorylation of p53 by
      ATM. PTC1, a rearrangement form of ret, may result in the disorder of cell damage
      repair and cell cycle checkpoint and destroy cell homeostasis.

PMID- 15142441
TI  - [Significance of stathmin gene overexpression in osteosarcoma cells].
AB  - BACKGROUND & OBJECTIVE: Stathmin, a signal transduction regulatory factor, plays
      a crucial role in cell division and malignant tumor development. This study was
      designed to analyze stathmin gene expression in the tissue of osteosarcoma, and
      to explore the growth inhibition by blocking stathmin expression with Stathmin
      antisense oligodeoxynucleotide (ASODN) on cultured human osteosarcoma cell line
      with stathmin gene overexpression. METHODS: Reverse transcriptase polymerase
      chain reaction (RT-PCR) and in situ hybridization methods were used to determine
      the expression of stathmin in two human osteosarcoma cell lines and 45
      osteosarcoma tissue specimens. Using stathmin gene overexpression in human
      osteosarcoma cell line SOSP-9607 as target cell and stathmin ASODN as gene
      expression blocking agent, cell growth inhibition of stathmin ASODN was
      determined by MTT method, and cell growth and mitotic character was analyzed by
      flow cytometry. RESULTS: Both osteosarcoma cell lines of SOSP-9607 and SOSP-9901
      showed stathmin gene overexpression by RT-PCR method and 24 of 45 osteosarcoma
      specimens were stathmin positive by in situ hybridization, while there were only
      2 in 10 normal tissues with mild positive signal. There was significant
      difference in stathmin gene expression between human osteosarcoma tissues and
      normal tissues (P< 0.05). The growth of osteosarcoma cells were suppressed by
      ASODN (P< 0.05,P< 0.01). The cell cycle of SOSP-9607 was blocked in metaphase and
      cell apoptosis was found. CONCLUSION: Stathmin gene displays high level
      expression in osteosarcoma, which may become a new target for the bio-treatment
      for osteosarcoma.

PMID- 15142442
TI  - [Effect of DAPK1 gene transfection on high-metastasis non-small lung cancer cell
      PGCl3].
AB  - BACKGROUND & OBJECTIVE: Loss of activity of death- associated protein kinase 1
      (DAPK1) may be an independent factor affecting survival of non-small cell lung
      cancer patients. DAPK1 over-expression can induce cell apoptosis and inhibit
      tumor cell metastasis. However, the mechanism of DAPK1 inhibiting metastasis was
      unclear yet. This study was designed to investigate the mechanism of DAPK1
      affecting PGCl3 cells' growth and metastasis. METHODS: Open read frame (ORF) of
      DAPK1 gene was recombined into eukaryotic express vector pcDNA3.1. The PGCl3 cell
      line, a high metastasis lung tumor cell line, was transfected with pcDNA3.1-DAPK1
      by lipofectamine2000. The growth curve of PGCl3 cells, colony formation assays,
      invasive, migration and adhesion ability were evaluated. Gelatinase secretion of
      PGCl3 cells treated with DAPK1 and expression of p53 and bcl-2 gene in PGCl3
      cells were determined. RESULTS: PGCl3 cells of pcDNA3.1-DAPK1-transfected group
      grew slower than blank group and pcDNA3.1-transfected group. The numbers of
      colony formation of pcDNA3.1-DAPK1-transfected group reduced in comparison with
      blank group and pcDNA3.1-transfected group (P< 0.05). Invasive ability of
      pcDNA3.1-DAPK1-transfected group was 68.5% to blank group, and pcDNA3.1
      transfected group was 88% to blank group. Migration ability of pcDNA3.1-DAPK1
      transfected group was 87.3% to blank group and pcDNA3.1-transfected group was
      95.7% to blank group. Adhesion ability of pcDNA3.1-DAPK1-transfected group was
      62.7% to blank group, and pcDNA3.1-transfected group was 91.2% to blank group.
      Changes in PGCl3 cells secreting gelatinase have not been observed in different
      groups. Expression of p53 gene was upregulated in pcDNA3.1-DAPK1-transfected
      group, while expression of bcl-2 gene was downregulated. CONCLUSION: DAPK1 gene
      over-expression could suppress PGCl3 cells malignant phenotype, inhibit PGCl3
      cells growth, invasive, migration and adhesion ability, upregulate p53 gene and
      downregulate bcl-2 gene. All of these changes may be the mechanism of inhibition
      of non-small cell lung cancer metastasis induced by DAPK1.

PMID- 15142444
TI  - [Screening hepatitis B virus X-interactive proteins by yeast two-hybrid system].
AB  - BACKGROUND & OBJECTIVE: Hepatitis B virus-encoded X protein is a promiscuous
      transactivator and contributes to the development of hepatocellular carcinoma.
      Protein-protein interaction seems to be crucial for HBx transactivation. The aim
      of this study was to screen and identify the proteins which interact with
      hepatitis B virus (HBV) X protein by yeast two-hybrid system. METHODS: HBV X gene
      was amplified by polymerase chain reaction (PCR). HBV X bait plasmid, named pAS2
      1-X, was constructed by yeast-two hybridization system 3 and verified by
      sequencing. pAS2-1-X was transformed into the yeast AH109, and X-BD fusion
      protein expressed in the yeast cells was confirmed by Western blot analysis.
      Yeast cells cotransformed with pAS2-1-X and normal human liver cDNA library were
      cultured in selective SC/-trp-leu-his-ade medium. The second screening was
      performed with beta-gal activity detection. The false positive clones were
      eliminated by segregation analysis and mating experiment. The real positive
      clones were amplified, sequenced, and analyzed with bioinformatics. RESULTS: Bait
      plasmid pAS2-1-X was successfully constructed. The result of Western blot
      analysis confirmed that pAS2-1-X correctly expressed X-BD fusion protein in the
      transformed yeast AH109. Ninety-seven clones grew in the selective SC/-trp-leu
      his-ade medium; however, only one clone past through the beta-gal activity
      detection, segregation analysis, and mating experiment. The inserted cDNA
      fragment of positive clone showed high homology with Fis gene. CONCLUSION: Fis
      protein is a novel protein which can interact with X protein in vivo by yeast two
      hybrid system.

PMID- 15142443
TI  - [Interaction of p53 with p53 response element like binding sequence at upstream
      of hepatitis B virus enhancer I].
AB  - BACKGROUND & OBJECTIVE: A p53 response element like binding sequence, 5'-TGCC(G)T
      TGCCT-3' was found at upstream of hepatitis B virus (HBV) enhancer I from 1047 to
      1059 nucleotides after analyzing the HBV genome by a computer program in our
      previous work. It indicated that the sequence could specifically bind P53 protein
      in vitro by electrophoretic mobility shift assay (EMSA) and electrophoretic
      mobility supershift assay (EMSSA). This study was designed to further investigate
      the interaction between P53 and p53 response element like binding sequence at
      upstream of HBV enhancer I. METHODS: HBV x gene enhancer and promoter which
      contains p53 response element like binding sequence TGCGT-TGCCT was in upstream
      of CAT enzyme in pX-CAT reporter plasmid. Firstly, we designed a point mutation
      in pX-CAT which change TGCGT TGCCT into TGTAT. TGTAT by polymerase chain reaction
      (PCR) in order to damage the p53 response element like sequence. After pX-CAT or
      mutation pX-CAT (mpX-CAT) transfected alone or cotransfected with pCMVp53 into
      HepG2 hepatoma cell, CAT activity was assayed to confirm the correlation of p53
      protein with this DNA sequence. In addition, an antisense sequence corresponding
      to the p53 response element like sequence in HBV was reconstructed into the
      pZeoSV2 vector (alpha pZeoXP) and transfected into HepG2.2.15 cell line to block
      the binding of P53 with this sequence, the stable transfected HepG2.2.15 cell was
      observed about P53/P21 expression, cell cycle distribution and apoptosis rates.
      RESULTS: CAT enzyme of HepG2 had an higher expression in cotransfection with
      pCMVp53 and pX-CAT than alone pX-CAT (1.353 VS 0.738,P< 0.05), but it was lower
      in mpX-CAT(0.304) and pCMVp53 (0.402). Compared with the control group, P53/P21
      expression and cell apoptosis rate decreased greatly in the stable transfected
      alpha pZeoXP HepG2.2.15 cell line (0.95% VS 7.84%), the cell number in S phase
      increased in the same cell line (16.37% VS 9.48%). CONCLUSION: Reporter gene
      expression of pX-CAT in intracellular could be promoted by P53, which further
      suggest that P53 could bind TGCC(G)T-TGCCT in upstream of HBV enhancer I and
      induce a prolonged P53 half life. Subsequently, P53 and p21 protein (downstream
      gene of P53) would have a higher expression and stronger activity.

PMID- 15142445
TI  - [Effect of EB virus latent membrane protein 1 on mitosis control of
      nasopharyngeal carcinoma cell line CNE1].
AB  - BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) latent membrane protein
      1(LMP1)is the only one of approved oncogene coded by virus gene in nasopharyngeal
      carcinoma (NPC). LMP1 is involved in the regulation of cell cycle but it is still
      unknown if LMP1 induces the disturbance of mitosis control and mitotic
      checkpoint. The aim of this study was to investigate the effect of EBV-LMP1 on
      mitosis control of NPC cell line CNE1 and the related pathogenesis of NPC.
      METHODS: Cell cycle and the function of mitotic checkpoint were assayed by flow
      cytometry in human NPC cells cultured in vitro, including CNE1 cell line (well
      differentiated cells of NPC, WHO classified it as keratinizing squamous cell
      carcinoma), CNE1-GL cell strain (CNE1 cell line transfected with an eukaryotic
      plasmid PAT-GFP-LMP1) and CNE-2Z cell line (poorly differentiated cells of NPC,
      WHO classified it as differentiated non-keratinizing carcinoma). Before
      investigating expression of proteins, the cells were synchronized at mitosis
      phase. The expression of mitotic regulators, P34(cdc2), cyclin B1, and p53 was
      subsequently determined using Western blot analysis. RESULTS: The G(2)/M ratio of
      CNE1-GL was significantly elevated compared with CNE1 (P< 0.05). A defective
      mitotic checkpoint was identified in CNE1-GL, and this phenomenon was also known
      as "mitotic slippage". Western blot analysis showed that the expression levels of
      P34(cdc2) and cyclin B1 proteins in CNE1-GL were 1.22+/-0.04 and 2.12+/-0.07
      times higher than that of those in CNE1, respectively,but there was no difference
      in the expression of p53 protein between CNE1-GL and CNE1. CONCLUSION: LMP1
      disturbs mitosis control and the function of mitotic checkpoint of CNE1 through
      up-regulating the expression of P34(cdc2) and cyclinB1 proteins.

PMID- 15142446
TI  - [Gadd45 mediated G2/M cell cycle arrest induced by BRCA1].
AB  - BACKGROUND & OBJECTIVE: It is considered that tumor suppressor gene BRCA1 is an
      important factor in the regulation of cell cycle checkpoint, but the molecular
      mechanism by which BRCA1 regulates cell cycle G(2)/M arrest is less known. The
      objective of this study was to investigate the effects of Gadd45 on the BRCA1
      induced cell growth suppression. METHODS: BRCA1 induction of Gadd45 protein was
      analyzed using Western-blot assay following cells transfection with BRCA1
      expression vector and cell sorting. Activation of the Gadd45 promoter by BRCA1
      was determined by CAT assay. Effect of antisense Gadd45 on the BRCA1-induced cell
      cycle G(2)-M arrest was examined by flow cytometry analysis. And the effects of
      antisense Gadd45 on BRCA1-mediated growth suppression in HeLa and HCT116 cell
      lines was determined by colony formation assay. RESULTS: Gadd45 protein was
      highly induced after expression of BRCA1. BRCA1 strongly activated the Gadd45
      promoter. Antisense Gadd45 substantially abrogated BRCA1-activated cell cycle
      G(2)-M arrest and BRCA1-induced cell growth suppression on HeLa and HCT116 cell
      lines. CONCLUSION: Gadd45 is a BRCA1-regulated downstream gene and mediates the
      role of BRCA1 in the control of cell cycle G(2)/M arrest and growth suppression.

PMID- 15142447
TI  - [2-DE profiling and differential analysis of human bronchial epithelial tissues
      in different stages of carcinogenesis].
AB  - BACKGROUND & OBJECTIVE: The carcinogenesis of bronchial epithelial cells is a
      complex multiple-stage process involving multiple genes, but its mechanism
      remains unclear. Studying this process with proteomic approaches may identify
      carcinogenesis-associated proteins, which are important for elucidating
      carcinogenic mechanism of human lung squamous carcinoma. This study was designed
      to optimize the protein preparation methods for bronchial epithelial tissues, to
      establish two-dimensional gel electrophoresis profiles of human bronchial
      epithelial tissues from different stages in carcinogenic process, and to perform
      differential analysis and provide a basis for identifying carcinogenesis
      associated proteins of lung squamous carcinoma. METHODS: After obtaining samples
      of the normal, metaplasia, dysplasia, carcinoma tissues of human bronchial
      epithelia, modified deoxycholate- trichloroaetic acid (DOC-TCA) precipitation was
      used to extract and purify the total proteins of bronchial epithelial samples.
      Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis (2-DE)
      was used to separate the total proteins of the samples. After silver staining,
      ImageMaster 2-DE image analysis software was applied to analyze 2-DE images. Some
      selected differential protein spots were identified by peptide mass fingerprint
      (PMF) based on matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF-MS) and database search. RESULTS: The total proteins
      extracted with the method described here were used to perform 2-DE. 2-DE patterns
      with high resolution and reproducibility from different stages were obtained. The
      average spots for normal epithelium, metaplasia, dysplasia and invasive carcinoma
      were 1189.50+/-39.89, 1227.00+/-37.90, 1273.00+/-43.31, and 1326.00+/-66.63,
      respectively. The test was repeated, which showed that there were average 1216 +/
      75 spots among 3 gels of the same metaplasia tissues and 1082 +/- 67 spots were
      matched. The average matching rate was 89.3% and protein spots in 3 gels had good
      reproducibility. The average position deviation of matched spots in different
      gels was 0.865+/- 0.247 mm in IEF direction, and 0.971+/- 0.104 mm in SDS-PAGE
      direction. The 2D images of 32 samples were compared, which showed a significant
      difference of the number of average protein spots among the four groups (P<
      0.05). The average differential spots between the low and advanced stages were
      31.50 +/- 7.67, 41.00 +/- 9.07, and 56.00 +/- 8.96, respectively. Twenty-three
      protein spots chosen randomly from dysplasia and invasive carcinoma groups were
      identified by PMF, some of which were involved in the cell proliferation,
      differentiation, cycle regulation, signal transduction and tumor occurrence.
      CONCLUSIONS: (1) Improved DOC-TCA precipitation is a preferable method for
      protein preparation from bronchial epithelial tissues. (2) We established well
      resolved, reproducible 2-DE profiles of human bronchial epithelial tissue in
      different stages of carcinogenesis. Some differentially expressed-proteins may be
      related to carcinogenesis of bronchial epithelia. These results provide a
      fundamental basis for further study of carcinogenic mechanism of lung squamous
      cancer and screening its specific marker.

PMID- 15142448
TI  - [Role and mechanism of nuclear factor kappa B in angiogenesis of human ovarian
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: It had been reported that nuclear factor kappa b (NF
      kappa B) was associated with in vitro angiogenesis, but its role in angiogenesis
      of human ovarian carcinoma (HOC) had not been reported yet. The objective of this
      paper was to investigate the role and the mechanism of NF kappa B in HOC
      angiogenesis in chick chorioallantcic membrane (CAM). METHODS: The HOC TYK cells
      were implanted into 10-day CAM by 1 x 10(9)/per egg to establish the HOC CAM
      model. (1) With 20 eggs, the levels of NF kappa B, integrin alpha V beta 3, basic
      fibroblast growth factor (bFGF) at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h time point
      after cells implanted were determined with ELISA. (2) The relationship among NF
      kappa B, bFGF,alpha V beta 3 and the effect of them on HOC angiogenesis in CAM
      were determined. Another 80 eggs were divided into 6 groups, normal saline (NS)
      (control group, 16 eggs), anti- NF kappa B (A group, 16 eggs), anti-bFGF (B
      group, 16 eggs), anti-NF kappa B + anti-bFGF(D group, 8 eggs) were added
      respectively into CAM at 6h time point after the cells implanted, and then anti
      integrin alpha V beta 3 (C group, 16 eggs), anti-NF kappa B +anti-alpha V beta 3
      (E group, 8 eggs) antibodies were added at 12h time point. Eight eggs from NS, A,
      B, C groups were taken out to determine the levels of NF kappa B, alpha V beta 3,
      bFGF at 48 h after the antibodies were added. The other eggs were incubated up to
      5 days, and the vessel area/area were determined with image analysis. RESULTS:
      (1)The levels of NF kappa B and bFGF increased significantly at 6h, and that of V
      beta 3 increase significantly at 12 h time point after implantation (P< 0.01)
      (0.185+/-0.01, 0.771+/-0.16, 0.231+/-0.02), the peaks of the three levels were
      reached at 48 h (P< 0.01) (0.337+/-0.01, 1.639+/-0.01, 0.349+/-0.01). The levels
      of bFGF was significantly higher than those of NF kappa B and alpha V beta 3 at
      each time point (P< 0.01), but there were no significant difference between NF
      kappa B and alpha V beta 3 (P >0.05). (2)The levels of NF kappa B,bFGF, and alpha
      V beta 3 in A and B groups were significantly lower than those of NS group (P<
      0.01) (0.098+/-0.02, 0.156+/-0.02, 0.329+/-0.01; 1.106+/-0.33, 0.412+/-0.01,
      1.591+/-0.13; 0.138+/-0.03, 0.114+/-0.02, 0.322+/-0.01). And the level of alpha V
      beta 3 in C group were significantly reduced compared with those of NS group (P<
      0.01) (0.119+/-0.02, 0.322+/-0.01), while the levels of NF kappa B and bFGF had
      no change between the two groups (P>0.05). The VA/A of the five groups of A, B,
      C, D, and E were significantly lower than that of NS group (P< 0.05) (26.10+/
      13.71, 34.12+/-4.85, 25.50+/-11.41,14.32+/-3.11, 24.36+/-4.95, 66.62+/-17.64),
      and that of D group were significantly reduced compared with A group (P< 0.05)
      (14.32+/-3.11, 26.10+/-13.71), but there were no significant difference among the
      four groups of A, B, C, and E (P >0.05). CONCLUSIONS: NF kappa B can stimulate
      the angiogenesis of ovarian carcinoma with bFGF by upregulating the expression of
      alpha V beta 3, bFGF, which can be used as a marker of angiogenesis and a therapy
      target molecule of ovarian carcinoma.

PMID- 15142449
TI  - [Expression of hMSH2 and hMLH1 in stomach cancer and their correlation with
      Helicobacter pylori infection].
AB  - BACKGROUND & OBJECTIVE: The carcinogenesis of gastric carcinoma is related to
      many factors. Helicobacter pylori (HP) infection is one of the factors causing
      gastric carcinoma, but the exact molecular mechanism is not clear. Mismatch
      repair genes are important in keeping the accuracy of DNA replication. They are
      associated with carcinogenesis of alimentary canal. In order to investigate the
      role of hMSH2 and hMLH1 in stomach cancer and the possible mechanism of
      carcinogenesis caused by HP infection, we tested cancer tissue, surrounding
      mucosa and chronic superficial gastritic mucosa with and without HP infection.
      METHODS: HP infection was determined with quick-ureolytase method.
      Immunohistochemistry staining was used to exam the expression of hMSH2 and hMLH1
      in tumor tissue and their surrounding mucosa and gastric mucosa. Chi-square was
      used for statistic analysis. RESULTS: The positive rate (67.1%) of hMSH2
      expression in cancer tissue was significantly higher than those of surrounding
      mucosa (35.5%) and gastritic mucosa (42.1%) (P< 0.05); the positive rate (81.1%)
      of hMSH2 expression in poor differentiation group was significantly higher than
      those in well middle differentiation group (54.5%) and mucoid carcinoma group
      (54.5%) (P< 0.05), but there was no significant difference between the latter two
      groups. There was no significant difference among the positive rates of hMLH1
      expression in cancer tissue (81.6%), in surrounding mucosa (90.8%), and in
      gastritic mucosa (89.5%) (P>0.05). The positive rate (47.1%) of hMLH1 expression
      in mucoid carcinoma group was significantly higher than those in well middle
      differentiation group (81.8%) and poor differentiation group (97.3%) (P< 0.05),
      but there was no significant difference between the latter two groups (P>0.05).
      In cancer tissue, the positive rate (56.8%) of hMSH2 expression in HP infection
      group was significantly lower than that without HP infection group (81.3%) (P<
      0.05); the positive rates of hMLH1 expression was 77.2% in HP infection group and
      87.5% in without HP infection group, but there was no significant difference
      between two groups (P >0.05). In surrounding mucosa, the positive rate of hMSH2
      expression was 29.5% in HP infection group and 43.8% in without HP infection
      group, as well as those of hMLH1 were 86.4% and 96.9%, there were no significant
      differences between the groups. In gastritic mucosa, the positive rate of hMSH2
      expression was 38.5% in HP infection group and 50.5% in HP-negative group, as
      well as those of hMLH1 were 88.5% and 91.7%; there was no significant difference
      between the groups. CONCLUSION: The expression of hMSH2 is associated with
      carcinogenesis of stomach cancer, and its high expression may be a potential
      marker of stomach cancer; HP infection inducing low expression of hMSH2 and hMLH1
      may be one of molecular mechanisms by which HP infection leads to stomach cancer.

PMID- 15142450
TI  - [Effect of epidermal growth factor receptor-selective tyrosine kinase inhibitor
      ZD1839 on nasopharyngeal carcinoma cells].
AB  - BACKGROUND & OBJECTIVE: ZD1839, an anilinoquinazoline, is an orally active,
      selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,
      which has been approved for the treatment of advanced non-small cell lung cancer
      by FDA. Nasopharyngeal carcinoma is of epithelial origin with overexpression of
      epidermal growth factor receptor and it remains unclear whether ZD1839 is useful
      in the treatment of nasopharyngeal carcinoma. The present study was designed to
      evaluate the effect of ZD1839 on nasopharyngeal carcinoma cell lines. METHODS:
      The effect of ZD1839 on nasopharyngeal carcinoma cells (CNE1, CNE2, SUNE1) was
      determined by MTT assay. The effect of ZD1839 combined with cisplatin (DDP) or 5
      fluouracil (5-FU) on nasopharyngeal carcinoma cell CNE2 was also evaluated. Burgi
      formula was adopted to analyze combination effect. The distribution of cell cycle
      and cell apoptosis rate were analyzed by flow cytometry. RESULTS: The
      proliferation of nasopharyngeal carcinoma cell lines CNE1, CNE2, and SUNE1 was
      inhibited by ZD1839, and the effect was dose-dependent. The value of IC50 for the
      effect of ZD1839 on nasopharyngeal carcinoma cell lines CNE1, CNE2, and SUNE1 was
      3.9 micromol/L, 5.6 micromol/L, and 5.5 micromol/L, respectively. ZD1839 could
      enhance the effect of DDP and 5-FU on CNE2 cells. The Q values by Burgi formula
      were 1.19+/-0.02 and 1.12+/-0.10, respectively. When CNE2 cells were treated with
      ZD1839 at the concentration of 0, 1.95, 3.9, 7.8, 15.6, 31.25 micromol/L, the
      percentages of G(0)/G(1) phase were (46.8+/-1.7)%, (48.8+/-1.6)%, (51.3+/-1.3)%,
      (54.0+/-1.3)%, (61.5+/-2.2)%, and (71.2+/-1.4)%, respectively; the percentages of
      S phase were (37.5+/-1.3)%, (35.8+/-1.6)%, (31.8+/-2.1)%, (34.3+/-2.7)%, (27.2+/
      2.9)%, and (27.6+/-2.4)%, respectively;the percentages of G(2)/M phase were
      (15.7+/-0.4)%, (15.3+/-0.1)%, (16.9+/-0.9)%, (11.7+/-1.4)%, (11.3+/-0.7)%, and
      (1.1+/-0.8)%, respectively. When CNE2 cells were treated with ZD1839 at the
      concentration of 0, 1.95, 3.9, 7.8, 15.6, 31.25, 62.5 micromol/L, the rates of
      CNE2 cell apoptosis were (1.6+/-0.3)%, (1.7+/-0.3)%, (2.3+/-0.4)%, (3.3+/-0.4)%,
      (3.9+/-0.8)%,(8.0+/-1.1)%,and(14.3+/-2.3)%, respectively. CONCLUSION: ZD1839
      inhibits the proliferation of nasopharyngeal carcinoma cells and enhances the
      effect of cytotoxic drugs.ZD1839 induces CNE2 cell cycle arrest in the G1 phase
      and higher concentration of ZD1839 could induce apoptosis.

PMID- 15142451
TI  - [Inhibition of anti-sense human telomerase reverse transcriptase (hTERT)
      retroviral vector on lung cancer cells].
AB  - BACKGROUND & OBJECTIVE: Inhibition of telomere length can be achieved through
      suppression of telomerase activity, which may result in the inhibition of
      immortal cell proliferation. In order to explore the possibility of the
      telomerase as a target for lung cancer therapy, we investigated the effects of
      anti-sense human telomerase reverse transcriptase (hTERT) on telomerase activity
      and cell proliferation of A549 lung cancer cell line. METHODS: The anti-sense
      hTERT cDNA, an 835 bp in the 5' region of hTERT mRNA was amplified by reverse
      transcription polymerase chain reaction (RT-PCR), before cloning into pLXSN
      retroviral vector in sense and anti-sense orientations. A549 cells, a human lung
      cancer cell line, were infected with recombinant virus obtained after
      transfection into packaging cell PT67. The expression of hTERT protein was
      determined by Western blot analysis. The telomerase activity was measured by
      telomerase repeat amplification protocol (TRAP). The cell proliferation was
      depicted by cell morphology under inverted microscopy as well as cell growth
      curve. Apoptosis was analyzed by flow cytometry and DNA electrophoresis. RESULTS:
      Compared with sense hTERT transduction, hTERT expression and telomerase activity
      significantly decreased in A549 cells after anti-sense hTERT transduction. The
      cell proliferation was markedly inhibited with evidence of apoptosis. CONCLUSION:
      Anti-sense hTERT exhibited significant inhibition of telomerase activity and cell
      proliferation, in addition to acceleration of apoptosis. This implied the
      possibility of hTERT as the potential target for gene therapy of lung cancer.

PMID- 15142453
TI  - [Trends analysis of common urologic neoplasm incidence of elderly people in
      Shanghai, 1973-1999].
AB  - BACKGROUND & OBJECTIVE: Few studies on trend analysis in cancer incidence of the
      elderly people in China. The purpose of this study was to analyze time trends in
      urologic cancer incidence of the elderly people during the period 1973-1999 in
      Shanghai. METHODS: The registered cancer cases were coded according to the 3
      digit rubrics of the ninth revision of the International Classification of
      Diseases (ICD-9). Population estimates were based on periodic censuses, with age-
      and sex-specific annual estimates derived by linear inter- and extrapolation for
      the remaining years. The age-standardized rates adjusted to the world population
      were calculated for nine 3-year periods. Annual percent changes in incidence were
      estimated by means of a linear regression of the respective rates on the mid
      point of calendar years, weighted by the number of cases. RESULTS: During the 27
      year period, cancers of prostate, bladder, and kidney have risen substantially
      among elderly male residents in Shanghai. The annual percent changes were 6.60%,
      1.15%, and 5.30%, respectively. Among the elderly women, the rate of kidney
      cancer increased rapidly, with the annual percent change of 4.87%. The 75 years
      and older age group in women had substantial increases in incidence rates of
      bladder cancer. CONCLUSION: From 1973 to 1999, the incidence rates of the
      commonly urologic cancers increased substantially among the elderly residents in
      Shanghai, except for female bladder cancer.

PMID- 15142452
TI  - [Association of drinking water source and colorectal cancer incidence: a prospect
      cohort study].
AB  - BACKGROUND & OBJECTIVE: The pollution of drinking water, for example river and
      pool, has long been recognized to be associated with an increased risk of
      colorectal cancer (CRC) in previous epidemiological studies. There is little
      prospect cohort study with person-years directly on the relative risks of
      different sources of drinking water for CRC. METHODS: From May 1989 to April
      1990, a screening for CRC was carried out among residents aged 30 and over 30
      years in 10 villages and towns of Jiashan in China. A total of 64115 residents
      who participated the screening were classified into 5 cohorts by the source of
      drinking water and were followed-up for CRC incidence through a tumor reporting
      system including a rapid reporting system of CRC Registry and for death instance
      through Death Registration of Jiashan. After 11 years of follow-up, person-years
      calculated with every cohort member, the incidence densities of CRC with
      different sources of drinking water were analyzed respectively. Poisson
      regression was used to control potential confounding variables including
      demography variables and smoke history and to attain crude and adjusted relative
      risks based on person-years. RESULTS: A trend was seen toward increasing
      incidence rates of colorectal cancer from municipal, river, channel, mixed water
      to well source in turn as shown as 29.61, 32.67, 33.45, 40.87, 58.67 per 100,000
      inhabitants, and only the role in risk of well water was marked different from
      municipal water (P< 0.05). After adjusted the confounding variables by multi
      Poisson regression, we found the significant risk of drinking well water for
      colon cancer, rectal cancer, and colorectal cancer. The relative risks were 1.741
      (95%CI 1.001-3.029), 2.228 (95%CI 1.432-3.466), and 2.022 (95%CI 1.432-2.854),
      respectively. CONCLUSION: Drinking well water long is a risk factor for
      colorectal cancer in Jiashan, especially for rectal cancer.

PMID- 15142454
TI  - [Multi-antibody combined determination of lymph node micrometastasis in patients
      with gastric cancer].
AB  - BACKGROUND & OBJECTIVE: Immunohistochemical staining is a simple method for
      determination of lymph node micrometastasis in gastric cancer; but the
      sensitivity is low. Whether this disadvantage can be improved using multi
      antibody combined determination is still controversial. This study was designed
      to determine the lymph node micrometastasis in patients with gastric cancer by
      the antibodies of cytokeratin 20 (CK20), epithelial membrane antigen (EMA), and
      carcinoembryonic antigen 72-4 (CA72-4)for clarifying the value of multi-antibody
      combined determination of micrometastasis. METHODS: A total of 466 lymph nodes
      was collected with operation from 44 gastric cancer patients from April 1991 to
      April 1994. All these lymph nodes showed no lymph node metastasis by routine
      histological examination. Immunohistochemical staining was performed on all the
      samples by the mouse antibodies of anti-CK 20, mouse anti-EMA, and mouse anti
      CA72-4, respectively. Then, the micrometastases were identified under microscope
      according to the color of the cells. The results were analyzed according to
      clinical, pathological, and follow-up data. RESULTS: Fifty-one (10.9%) lymph
      nodes of 18 (40.9%) cases showed micrometastasis. The number of micrometastatic
      lymph nodes were detected by CK20, CA72-4, and EMA was 40 (8.6%), 27 (5.8%), and
      21 (4.5%), respectively. There was no significant correlation between the lymph
      node micrometastasis and clinical data, such as gender, age, tumor site,
      histological differentiation, and stage (P >0.05). The 5-year survival rate of
      the patients with lymph node micrometastasis was lower than that of the patients
      without lymph node micrometastasis(61.11+/-11.49% vs. 92.31+/-5.23%, P=0.0113).
      The 5-year survival rate of the patients with 3 or more positive micrometastatic
      nodes was lower than that of the patients with less than 3 positive
      micrometastatic nodes (44.44+/-16.56% vs. 77.78+/-13.86%,P=0.0196). CONCLUSION:
      Immunohistochemical staining marked by different antibodies can be an useful
      method to seek more micrometastatic lymph nodes in gastric cancer patients.

PMID- 15142455
TI  - [Multivariate regression analysis of recurrence following curative surgery for
      colorectal cancer].
AB  - BACKGROUND & OBJECTIVE: Recurrence is a very important prognostic factor for
      colorectal cancer patients after operation. The selection of patients for
      individualized follow-up and adjuvant therapy after curative resection of
      colorectal carcinoma depends on prognostic factors for recurrence. The objective
      of this study was to investigate the clinicopathologic factors related to
      recurrence following curative surgery for colorectal cancer. METHODS: The
      clinicopathologic factors and follow-up data of 692 cases of colorectal cancers
      after surgical treatment from 1991 to 1999 were retrospectively analyzed by
      univariate and multivariate methods. RESULTS: The overall 3-year and 5-year
      survival rates were 33.1% and 19.7% in recurrent group, and 92.8% and 86.1% in
      nonrecurrent group, respectively. Univariate analysis showed that Dukes' stage,
      lymph node metastasis, tumor location, histological differentiation, gross
      findings and depth of bowel wall invasion were significantly associated with
      recurrence after operation. Multivariate analysis showed that lymph node
      metastasis and tumor location were prognostic factors for recurrence after
      operation. In separate analysis of distant metastasis and local recurrence with
      multivariate method, lymph node metastasis was an prognostic variable for both
      distant metastasis and local recurrence. Depth of bowel wall invasion was
      associated with distant metastasis, and tumor location was associated with local
      recurrence. CONCLUSION: Lymph node metastasis is the most important prognostic
      factor for recurrence or distant metastasis and local recurrence after operation
      for the patients with colorectal carcinoma. Depth of bowel wall invasion is an
      important prognostic factor for distant metastasis. Rectal cancer patients should
      be considered to have additional risks for local recurrence.

PMID- 15142456
TI  - [Relationship of expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: C-erbB2, C-erbB3, and C-erbB4 are numbers of epidermal
      growth factor family. It has been confirmed that C-erbB2 was related to ovarian
      carcinoma, but the relationship of C-erbB3 and C-erbB4 with ovarian carcinoma is
      unclear. The objective of this study was to explore the relationship of
      expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian carcinoma. METHODS:
      Streptavidin-peroxidase immunohistochemistry method was used to determine the
      expression of C-erbB2, C-erbB3, and C-erbB4 in 49 cases of ovarian malignant
      neoplasms, 21 cases of ovarian benign neoplasms, and 19 cases of normal ovarian
      tissues (control), then the relationship of expression of C-erbB2, C-erbB3, C
      erbB4 and clinicopathologic parameters in ovarian neoplasm was analyzed. RESULTS:
      (1) The positive expression rates of C-erbB2, C-erbB3, and C-erbB4 in ovarian
      malignant neoplasms were 75.51%, 69.39%, and 65.31%, respectively, and they were
      higher than that in ovarian benign neoplasms (19.05%, 23.81%, and 23.81%,
      respectively) and control (21.05%, 15.79%, and 21.05%, respectively)(P< 0.05).
      (2) There was not significant difference between the expression of C-erbB2, C
      erbB3, and C-erbB4 in ovarian malignant neoplasms and its pathologic type and
      grade (P >0.05). (3) The positive expression rates of C-erbB2, C-erbB3, and C
      erbB4 in the patients with late stage or large amount of ascetic volume ( >500
      ml) were 90.0% and 91.3%, respectively, and those also were higher than that in
      early stage or ascetic volume< 500 ml (P< 0.05). (4) The cumulative survival time
      of the patients with positive expression of C-erbB2 or C-erbB4 was longer than
      that without expression (P< 0.01). The analysis of Cox model showed that
      expressions of C-erbB2 and C-erbB4 in ovarian malignant were also independent
      prognosis factors for ovarian cancer. CONCLUSION: The C-erbB family would play an
      importation role in ovarian malignant neoplasms, and also was related to poor
      prognosis in ovarian cancer.

PMID- 15142457
TI  - [Relationship between interleukin-10 level in ascites of patients with primary
      ovarian epithelial carcinoma and immune defect in peritoneal cavity].
AB  - BACKGROUND & OBJECTIVE: As a multifunctional Th2-cytokine, interleukin-10 (IL
      10)plays a major role in the immune response. It is well known that IL-10 is an
      immunosuppressive cytokine, and participates in the development and progression
      of various tumors. In this study, we investigated the relationship between the IL
      10 level in the ascites of the patients with primary ovarian epithelial carcinoma
      (POEC) and immune defect in the peritoneal cavity. METHODS: The IL-10 levels in
      serum and ascites of 32 patients with POEC, in culture supernatants of 4
      different ovarian carcinoma cell lines and in serum of 10 patients with ovarian
      epithelial benign tumor and 10 health women (control) were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: (1) IL-10 level in ascites was
      significantly higher than that in serum of patients with POEC, (159.78+/-51.20
      ng/L vs 12.01+/-4.38 ng/L, P=0.000). IL-10 level in serum of the patients with
      POEC (12.01+/-4.38 ng/L) was significantly higher than that of the patients with
      benign tumor (3.79+/-2.40 ng/L, P=0.000) and control (4.45+/-2.69 ng/L, P=0.003).
      There was no significant difference of IL-10 level in serum between ovarian
      benign tumor and control (P=0.529). (2) IL-10 level in ascites of the patients
      with POEC was correlated with FIGO stage but not correlated with histological
      grade. (3) IL-10 was detectable in culture supernatants of 4 different ovarian
      cancer cell lines (3ao, SKOV3, CAOV3 and OVCAR). CONCLUSION: High level of IL-10
      in ascites of the patients with POEC is probably associated with immune defect in
      their peritoneal cavity, ovarian cancer cells may promote metastasis in
      peritoneal cavity by secreting IL-10.

PMID- 15142458
TI  - [Diagnostic application of detecting AgNOR in peripheral blood T lymphocyte in
      patients with esophageal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Evaluation of the quantitative distribution of interphase
      AgNOR (argyrophilic nucleolar organizer regions) has been widely used for
      diagnostic and prognostic purposes of tumor. It has been proven by tumor
      immunology that tumor can induce host immunosuppression. T lymphocyte immune
      activity can be reflected by detecting AgNOR expression in nucleolar organizer
      regions. There are few reports about AgNOR expression in peripheral blood T
      lymphocyte of the patients with esophageal carcinoma. In this investigation,
      AgNOR expression in peripheral blood T lymphocyte was systematically evaluated in
      a serial of patients with esophageal carcinomas to determine its value in
      diagnosis of the patients. METHODS: AgNOR expression in peripheral blood T
      lymphocyte of 276 patients with esophageal carcinoma and 75 healthy controls were
      measured by microphotometry with the technique of silver stain. At the same time,
      carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tumor
      specific growth factor (TSGF) were also measured by microparticle enzyme immune
      analysis, bio-antibody sandwich, and chemo-chromatometry. RESULTS: (1) AgNOR
      expression in peripheral blood T lymphocyte of the patients with esophageal
      carcinoma (5.64+/-0.89) were much lower than that of control group (7.07+/
      0.81)(P=0.000). The positive rate, sensitivity, and specificity were 67.4%,
      0.674, and 0.920, respectively. Youden index was 0.59 and the area under receiver
      operator characteristic (ROC) curve was 0.886. (2) The positive rate of AgNOR
      (67.4%) was higher than those of CEA (12.86%), SCC (15.04%), and TSGF (36.49%) in
      patients with esophageal carcinoma (P< 0.001). There was no relationship between
      AgNOR expression and CEA, SCC, and TSGF (P>0.05). (3) AgNOR expression has a
      higher positive rate in patients with esophageal carcinoma than the combined
      positive rate of CEA, SCC, and TSGF (P = 0.018), but has a similar positive rate
      with those of AgNOR+CEA, AgNOR+SCC, or AgNOR+CEA+SCC, with no statistical
      difference (P >0.05). Combination of all these four indicators is much superior
      to determination of AgNOR expression alone (P=0.000), its sensitivity, Youden
      index, and the area under receiver operator characteristic curve were 0.875,
      0.77, and 0.955, respectively. CONCLUSIONS: There is notable immunosuppression in
      patient with esophageal carcinoma. Detecting AgNOR expression of peripheral blood
      T lymphocytes has value in cell immune function of esophageal carcinoma patients
      and suitable application value in screening and diagnosis of esophageal carcinoma
      patient. It is sophisticatal far screening method for esophageal carcinoma in
      combination with AgNOR SCC, CEA and TSGF detection.

PMID- 15142459
TI  - [Surgery for primary adenoid cystic carcinoma of cervical trachea].
AB  - BACKGROUND & OBJECTIVE: There were few reports about surgery for primary adenoid
      cystic carcinoma of cervical trachea. This study was designed to evaluate the
      efficacy of surgical resection of a series of 13 patients with primary adenoid
      cystic carcinoma of cervical trachea. METHODS: Thirteen patients who underwent
      surgical resection with biopsy-proven primary adenoid cystic carcinoma of
      cervical trachea were reviewed retrospectively. RESULTS: Of 13 patients, 6
      patients showed that tracheal invasion were more than 40 mm length, 7 less than
      40 mm length. Seven patients showed extratracheal invasion, 2 showed distance
      metastases, and 1 showed metastases in regional lymph nodes. Nine patients were
      treated with sleeve resection of trachea with primary anastomosis (average length
      of 34.8 mm resected), of which 3 underwent laryngeal release and 8 reserved
      laryngeal function; 2 received laryngectomy with end tracheostomy and 2 received
      partial tracheal resection and a patch of autologous tissue reconstruction. Of 13
      patients, 4 patients were treated with complete resection and 9 with incomplete
      resection alone or combined by postoperative irradiation. No death occurred
      during operation. Two tracheal stenoses and 1 laryngeal recurrent nerve palsy
      after operation were observed. Seven patients died after therapy, of which 6
      patients failed to local management, 1 case died of distance metastases. The
      total 5- and 10-year survival rates were 69.2% (9/13) and 50.0% (5/10),
      respectively. The 5- and 10-year survival rates were 75.0% (3/4) and 75.0% (3/4)
      for complete resection group, 55.0% (5/9) and 33.0% (2/6) for incomplete
      resection group, 83.3% (5/6) and 83.3% (5/6) for non-extratracheal invasion
      group, 57.1% (4/7) and 0% for extratracheal invasion group (P=0.001). CONCLUSION:
      Sleeve resection of trachea with primary reconstruction is the major treatment of
      the patients suffering from primary cervical tracheal adenoid cystic carcinoma
      with the long-term survival and function reservation.

PMID- 15142460
TI  - [Clinical characteristics and multivariate analysis of prognostic factors in
      recurrent laryngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: The recurrence is an important factor affecting the
      prognosis of laryngeal carcinoma. There are few reports on the clinical
      characteristics and the prognostic factors of recurrent laryngeal carcinoma. The
      purpose of this study was to analyze the clinical features and prognostic factors
      of recurrent laryngeal carcinoma. METHODS: The data of 80 patients with recurrent
      laryngeal carcinoma between 1990 and 1997 were retrospectively investigated.
      Survival analysis was performed by Kaplan-Meier method; comparison among/between
      groups was performed using log-rank test; multivariate analysis was carried out
      using Cox proportional hazard model. RESULTS: The recurrence sites included
      locoregional recurrence, neck lymph node and distant metastases. The 3-year and 5
      year overall survival rates for patients with recurrent laryngeal carcinoma were
      50.6% and 34.6%, respectively. The 5-year disease-specific survival rates for the
      patients treated with surgery, surgery + radiotherapy, and surgery +chemotherapy
      (30 cases) was 73%. The recurrence of laryngeal carcinoma were developed within 1
      156 months, the median time of recurrence was 11 months; there were 36
      locoregional recurrence, 36 neck lymph node recurrence, 4 locoregional recurrence
      associated with neck lymph node recurrence, 1 locoregional recurrence associated
      with distant metastases, 3 neck lymph node recurrence associated with distant
      metastases. Univariate analysis revealed that the factors impacting the prognosis
      were recurrent site, duration of recurrence gaps, treatment modality of
      recurrence, and age (P< 0.05). The neck lymph node recurrence group, peristomal
      recurrence group, distant metastases group, radiotherapy and chemotherapy after
      recurrence group had a poorer prognosis than locoregional recurrence group,
      larynx recurrence group, without distant metastases group, and surgery group (P<
      0.05). Multivariate analysis showed that age > or =60 years old, duration of
      recurrence gap < 12 months, distant metastases and radiotherapy or chemotherapy
      modality after recurrence were independently associated with decreased survival
      rates (P< 0.05). CONCLUSION: Surgery or surgery dominated multi-modality therapy
      was the principal treatment modality for recurrence laryngeal carcinoma. Age > or
      =60 years old, duration of recurrence gap < 12 months, distant metastases and
      salvage therapy by radiotherapy and chemotherapy but not surgery were independent
      factors affecting the prognosis.

PMID- 15142461
TI  - [Relationship of matrilysin with invasion, metastasis, and prognosis in laryngeal
      cancer].
AB  - BACKGROUND & OBJECTIVE: Matrilysin (matrix metalloproteinases-7, MMP-7) might
      play an important role in invasion and metastasis of tumor and is thought to be
      related to prognosis of many kinds of carcinomas. This study was designed to
      investigate the significance of MMP-7 expression in the invasion and metastasis
      of laryngeal cancer and the relationship of MMP-7 expression with the prognosis
      of laryngeal cancer. METHODS: The expression of MMP-7 in 70 samples with paraffin
      embedded laryngeal cancer and corresponding para-tumor normal mucosas were using
      immunohistochemical technique. The mRNA expression of MMP-7 were examined by
      reverse transcription-polymerase chain reaction (RT-PCR) in 24 frozen specimens
      of laryngeal cancer and corresponding para-tumor normal mucosas. RESULTS: (1) The
      immunohistochemical staining of MMP-7 was observed in 77.1% (54/70) of cancer
      tissues, which was significantly higher than that (5.7%, 4/70) of para-tumor
      normal mucosas (P< 0.01). The mRNA expression of MMP-7 was detected in 75.0%
      (18/24) of cancer tissues, which was also significantly higher than that (4.2%,
      1/24) of para-tumor normal mucosas (P< 0.01). (2) The expression of MMP-7 in
      protein level was hot only higher in T3-T4 group than that in T1-T2 group (P<
      0.01) but also higher in nodal metastases group than that in group without nodal
      metastases (P< 0.01). (3) The mRNA expression of MMP-7 was significantly higher
      in T3-T4 group than that in T1-T2 group (2.908 +/- 0.891 vs.1.662 +/- 0.508, P<
      0.01) and was significantly higher in nodal metastases group than that in group
      without nodal metastases (2.958 +/- 0.827 vs. 1.887 +/- 0.769,P< 0.01). (4)
      Kaplan-Meier survival curve showed that the prognosis of group with MMP-7 protein
      high expression was poorer than that in group of MMP-7 protein weak or negative
      expression (log-rank=4.7559, 8.9513; P=0.0292, 0.0028). No significant difference
      was found between group with MMP-7 protein weak expression and group with that
      negative expression (log-rank=0.0314, P= 0.8593). CONCLUSION: MMP-7 possesses
      close relationship with the invasion, metastasis, and prognosis of laryngeal
      cancer, and it may be served as a marker in estimating the invasive and
      metastatic potency and prognosis of laryngeal cancer.

PMID- 15142462
TI  - [Clinical analysis of xerostomia in patients with nasopharyngeal carcinoma after
      radiation therapy].
AB  - BACKGROUND & OBJECTIVE: There is few report on the xerostomia of the patients
      with nasopharyngeal carcinoma after conventional radiation therapy. Xerostomia is
      a serious, permanent, and ubiquitous sequelae in the patients with nasopharyngeal
      carcinoma after conventional radiation therapy. It has a significant impact on
      the patient's quality of life. This study was designed to investigate the
      severity of xerostomia and its impact on the quality of life in patients with
      nasopharyngeal carcinoma after conventional radiation therapy. METHODS: One
      hundred and thirty-six patients with nasopharyngeal carcinoma, treated by
      conventional radiation therapy in Cancer Center, Sun Yat-sen University, were
      surveyed by interview at the outpatient. A questionnaire and a visual analog
      scale (VAS) were used in analysis of xerostomia and xerostomia-related problems.
      RESULTS: Of 136 patents, 73.5% of the patients experienced a moderate to severe
      degree of xerostomia. 82.4% of the patients had to sip water to facilitate
      speech; 92.6% of the patients had to sip water to facilitate chewing and
      swallowing; 91.2% of the patients changed their feeding pattern (can eat only
      mashed food); 61.3% of the patients had to wake up to drink water because of dry
      mouth; 75.0% of the patients had teeth deteriorated. CONCLUSION: 73.5% of the
      patients with nasopharyngeal carcinoma after conventional radiation therapy
      experienced a moderate to severe degree of xerostomia. Xerostomia has a
      significant impact on the patient's speech, deglutition, sleep, and increases the
      morbidity rate of the tooth.

PMID- 15142463
TI  - [CD4+CD25+T regulatory cells in peripheral blood of B-NHL patients with or
      without chemotherapy].
AB  - BACKGROUND & OBJECTIVE: It is well known that the patients with B-Non-Hodgkin's
      Lymphoma (B-NHL) usually have a poor immune response. CD4(+)CD25(+)-Tregs is a
      new type of suppressor cell. It plays an important role in the tumor immune
      suppression. But its distribution and the mechanism of immune suppression in B
      NHL are still unknown. The present study was designed to evaluate the proportion
      of Tregs in peripheral blood of the patients with B-NHL with or without
      chemotherapy to investigate the mechanism of immune suppression in B-NHL and the
      effect of chemotherapy on immune system and provide evidence for effective
      intervention in immune function. METHODS: The peripheral blood was collected from
      39 patients with B-NHL before chemotherapy, 32 patients with B-NHL who achieved
      partial remission (PR) or complete remission (CR) after 4-6 cycles of
      chemotherapy, and 25 healthy people. The population of CD4(+), CD8(+),
      CD4(+)CD25(+), and CD4(+)CD25(+)CTLA4(+) T cells was evaluated by flow cytometry.
      RESULTS: The total number of lymphocyte, the proportion of CD4(+)T cells, and the
      ratio of CD4/CD8 in the group of B-NHL before chemotherapy was significant less
      than those of the healthy group (1.3+/-0.39 x 10(9) versus 2.1+/-0.41 x 10(9);
      27.5%+/-4.1% versus 32.9%+/-5.8%; 0.9+/-0.21 versus 1.31+/-0.4), but the
      percentages of CD4(+)CD25(+)-Tregs and CD4(+)CD25(+)CTLA4(+)-T cells were
      significantly higher than those of the healthy donors (14.7%+/-3.1% versus 8.4%+/
      2.5%; 7.4%+/-1.6% versus 5.1%+/-1.4%). In the group of chemotherapy, although the
      CD4/CD8 ratio (1.19+/-0.3) was almost near to that of the healthy group, the
      total number of lymphocytes (0.8+/-0.53 x10(9)) was less than those of the other
      two groups, and the proportions of CD4(+)CD25(+)-Tregs (20.3%+/-4.1%) and
      CD4(+)CD25(+)CTLA4(+)-T cells (11.5%+/-2.2%) were higher than those of the other
      two groups. CONCLUSION: The population of CD4(+)CD25(+)-Tregs in peripheral blood
      of the patients with B-NHL with or without chemotherapy was significantly higher
      than those in healthy donors, which may be one of the important reasons of
      immunosuppression in B-NHL.

PMID- 15142464
TI  - [Mycoplasma infection and cancer].
AB  - Mycoplasmas are widespread in nature as conditional pathogen, which may be the
      unique prokaryote that can cohabit with eukaryote and interact permanently with
      mammalian cells. Mycoplasma infection can be detected in many tumor tissues,
      continuous infection of mycoplasma can lead to transformation of mammalian cells,
      up-regulating expression of oncogenes, and some biologic changes of tumor cells,
      suggesting association of mycoplasma infection with tumorigenesis.

PMID- 15142465
TI  - [Dosimetric evaluation for three dimensional conformal, conventional, and
      traditional radiotherapy plans for patients with early nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Traditional external beam irradiation techniques for
      nasopharyngeal carcinoma have a lot of shortcomings, and improving external beam
      techniques have become an endeavor to enhance curative effectiveness. This study
      was designed to compare the dose distribution of three dimensional conformal
      radiotherapy (3D CRT) with traditional and conventional radiotherapy plans in the
      patients with early nasopharyngeal carcinoma using three dimensional treatment
      planning system. METHODS: Twenty-two patients with early nasopharyngeal carcinoma
      were selected. Traditional, conventional, and 3D CRT plans were made for each of
      them and compared with respect to target coverage (V95), normal tissue sparing
      (D50, D33, and D5, etc), normal tissue complication probability (NTCP). RESULTS:
      Dosimetric comparison indicated that the V95 of PTVnx60 and PTVnx50 for three
      different plans were 90.29% and 77.67% (traditional), 98.44% and 98.85%
      (conventional), 99.98% and 99.63% (3D CRT), respectively; and both conventional
      and 3D CRT had satisfied dose coverage of target volume especially in subclinical
      lesion region compared with traditional radiotherapy. With respect to normal
      tissue sparing, 3D CRT and conventional treatment plans could spare more
      brainstem, temporal lobe, optic chiasm, and pituitary than traditional plans; and
      3D CRT could spare more parotid gland and temporomandibular joint than
      traditional and conventional treatments. CONCLUSION: Considering the dose
      distribution of the three treatment plans, both conventional and 3D CRT had
      satisfied dose coverage of target volume especially in subclinical lesion region
      compared with traditional radiotherapy, and 3D CRT plans can spare more normal
      tissues such as parotid gland and temporomandibular joint etc, and decrease their
      NTCP while it get the same dose distribution in target volume as traditional and
      conventional plans do in the treatment of early nasopharyngeal carcinoma.

PMID- 15142466
TI  - Psychiatric genetics: what to expect.

PMID- 15142467
TI  - Atypical neuroleptic medication and psychosis in adolescence.

PMID- 15142468
TI  - Perinatal risk factors for schizophrenia: how specific are they?
AB  - The association between exposure to perinatal risk factors and increased
      vulnerability for schizophrenia is now documented by a large body of
      epidemiologic studies. However, the diagnostic specificity of this association
      may be questioned, because subjects with a history of exposure to early
      environmental risk factors are at an increased risk for other psychiatric
      disorders with childhood or adult onset, such as autism, anorexia nervosa, or
      affective disorders. Because a given risk factor may be associated with several
      adverse health outcomes, these findings do not preclude the existence of a causal
      relationship between perinatal risk factors and schizophrenia. This lack of
      diagnostic specificity suggests that the clinical expression of the vulnerability
      induced by early risk factors depends on gene-environment interactions or
      interaction between this prenatally determined vulnerability and exposure to
      later environmental risk factors.

PMID- 15142469
TI  - Developmental precursors of psychosis.
AB  - Subtle developmental (motor, emotional, cognitive, and behavioral) abnormalities
      are often present in apparently healthy individuals who later develop psychosis,
      suggesting that some aspects of causation are established before overt psychosis.
      These impairments may restrict information processing and social achievements
      years before manifesting psychosis. The main known risk factors in the
      development of schizophrenic psychosis are genetic factors, pregnancy and
      delivery complications, slow neuromotor development, and deviant cognitive and
      academic performance. However, their effect size and predictive power are small.
      Developmental precursors are not necessarily specific to schizophrenia, but also
      common to other psychotic disorders. No powerful risk factor, premorbid sign, or
      risk indicator has been identified that is useful for prediction of psychoses in
      the general population.

PMID- 15142470
TI  - Genetic abnormalities of chromosome 22 and the development of psychosis.
AB  - A microdeletion at chromosome 22q11 is the most frequently known interstitial
      deletion found in humans, occurring in approximately one of every 4000 live
      births. Its occurrence is associated with a characteristic facial dysmorphology,
      a range of congenital abnormalities, and psychiatric problems, especially
      schizophrenia. The prevalence of psychosis in those with 22q11 deletion syndrome
      is high (30%), suggesting that haploinsufficiency of a gene or genes in this
      region may confer a substantially increased risk. In addition, several studies
      provide evidence for linkage to schizophrenia on 22q, suggesting that a gene in
      this region could confer susceptibility to schizophrenia in nondeleted cases.
      Recent studies have provided compelling evidence that haploinsufficiency of TBX1
      is likely to be responsible for many of the physical features associated with the
      deletion. However, although a number of genes have been implicated as possible
      schizophrenia susceptibility loci, further confirmatory studies are required.

PMID- 15142471
TI  - Theory of mind, social development, and psychosis.
AB  - The difficulty in interpreting other people's mental states found in children
      with autism and in people affected by schizophrenia may be explained in terms of
      a unique mental process called Theory of Mind. The paper discusses the main
      operational issues of such a peculiar aspect of social cognition, the Theory of
      Mind, and its implication in schizophrenia, including a review of its related
      neural structures. Theory of Mind abilities may be a relevant aspect of social
      interaction involving people affected by schizophrenia, and they need to be
      further investigated in clinical research.

PMID- 15142472
TI  - Impact of medical comorbid disease on antidepressant treatment of major
      depressive disorder.
AB  - A major factor in evaluating and treating depression is the presence of comorbid
      medical problems. In this paper, the authors will first evaluate studies showing
      that medical illness is a risk factor for depression. The authors will review a
      series of randomized, controlled studies of antidepressant treatment in subjects
      with major depressive disorder (MDD) and comorbid medical illnesses (myocardial
      infarction, stroke, diabetes, cancer, and rheumatoid arthritis). Most of these
      studies report an advantage for an active antidepressant over placebo in
      improvement of depressive symptoms. The authors also will review a series of
      studies in which the outcome of antidepressant treatment is compared between
      subjects with MDD with and without comorbid medical illness. In these studies,
      subjects with medical illness tend to have lower improvement of depressive
      symptoms and higher rates of depressive relapse with antidepressant treatment
      compared with MDD subjects with no medical comorbidity. In addition, the authors
      will review hypotheses on the mechanism of the interaction between medical
      illness and clinical response in MDD. The paper will conclude that medical
      comorbidity is a predictor of treatment resistance in MDD.

PMID- 15142473
TI  - Should selective serotonin reuptake inhibitors be prescribed to all patients with
      ischemic heart disease?
AB  - Recent studies have uncovered more and more evidence demonstrating the adverse
      relationship between depression and ischemic heart disease. One of the most
      significant mechanisms that may explain the adverse relationship is the increased
      platelet activity, otherwise known as aggregation, observed to occur in patients
      with depression or ischemic heart disease. Platelet activity is further elevated
      in patients with depression and ischemic heart disease. Selective serotonin
      reuptake inhibitors are antidepressants and also act like platelet inhibitors.
      The results of large-scale clinical trials suggest that the use of selective
      serotonin reuptake inhibitors may reduce cardiac events in post-myocardial
      infarction patients or in those with unstable angina that may be related to the
      effects of selective serotonin reuptake inhibitors on platelet aggregation.

PMID- 15142474
TI  - The interface of psychiatry and irritable bowel syndrome.
AB  - The interface of psychiatry and irritable bowel syndrome (IBS) is well
      established, with psychiatric comorbidity approaching 20% to 60%. Anxiety
      disorders, depressive disorders, and somatoform disorders are the more frequently
      occurring comorbid conditions. Moreover, psychosocial stressors and history of
      trauma and abuse play a significant role in the onset and perpetuation of IBS
      symptoms. The psychiatric management of IBS more effectively uses a collaborative
      approach between a mental health practitioner and a primary care clinician or
      gastroenterologist. Psychiatric treatment includes the use of pharmacotherapy
      with antidepressants or anxiolytics, psychotherapy, and attention to psychosocial
      stressors. Psychiatric interventions have consistently demonstrated effectiveness
      in reducing IBS symptoms and improvement of patient functioning.

PMID- 15142477
TI  - Effect of Amoxicillin and Coamoxiclav on the Aerobic and Anaerobic Nasopharyngeal
      Flora.

PMID- 15142478
TI  - Eradication of Streptococcus pneumoniae in the Nasopharyngeal Flora of Children
      with Acute Otitis Media after Amoxicillin/Clavulanate Therapy.

PMID- 15142476
TI  - Psychopharmacology of borderline personality disorder.
AB  - Psychopharmacology is widely used in the treatment of borderline personality
      disorder. However, support for this form of treatment has been largely based on
      case reports, case series, and open-label clinical trials. This evidence-based
      review examines the most recent randomized controlled trials of
      psychopharmacology in the treatment of borderline personality disorder, with a
      goal of highlighting the most promising pharmacotherapy for use in current
      clinical practice, as well as for future large-scale research testing. The
      results and limitations of the randomized controlled trial data are presented
      along with case vignettes illustrating the complexity of the disorder and the
      heterogeneity of its treatment. To date, there is at least some evidence-based
      support for the use of antipsychotics (conventional and atypical), monoamine
      oxidase inhibitors, serotonin reuptake inhibitors, and omega-3 fatty acids in the
      treatment of borderline personality disorder.

PMID- 15142475
TI  - Psychotic symptoms in patients with medical disorders.
AB  - Psychotic symptoms frequently occur in patients with comorbid medical disorders
      and present a diagnostic and treatment challenge. They may be a part of an
      independent psychiatric illness associated with the underlying medical condition
      or induced by substance use or medications. The presence of psychotic symptoms
      can contribute to misdiagnosis or complicate the management of the comorbid
      medical illness. Psychiatrists must be familiar with the assessment and
      management of psychotic disorders in patients with comorbid medical disorders.
      Medications that may be used to treat psychosis include antipsychotic agents,
      benzodiazepines, or possibly certain anticonvulsants. Selecting the appropriate
      medication requires knowledge of the pharmacokinetics of different agents and
      their side effect profile. Understanding the neuropsychiatric effects of
      medications and drug-drug interactions may help in preventing psychotic symptoms.

PMID- 15142479
TI  - Prevention and Treatment of Postsurgical Head and Neck Infections.
AB  - Postoperative wound infection is an important cause of postsurgical morbidity.
      Efforts to reduce the incidence of wound infection are enhanced through
      appropriate preoperative preparation, adherence to excellent surgical technique,
      and the provision of outstanding postoperative care. Many head and neck surgical
      procedures are undertaken in an environment contaminated by saliva containing a
      large inoculum of potentially pathogenic bacteria. Prospective randomized
      clinical trials have demonstrated that perioperative antibiotic prophylaxis
      reduces the risk for postoperative wound infection. Effective antibiotic
      prophylaxis requires that the antibiotic be effective against normal oral flora.
      Antibiotics should be administered before wound contamination. The dose of the
      antibiotic should exceed the minimal inhibitory concentration needed for the
      normal flora. The antibiotic administration can cease within 24 hours of surgery.

PMID- 15142480
TI  - Rapid Detection and Diagnosis of Group A Streptococcal Pharyngitis.
AB  - This article reviews techniques of rapid testing and the effective diagnosis of
      streptococcal pharyngitis. Despite 50 years' study of streptococcal pharyngitis
      and 20 years' experience with rapid tests for its diagnosis, the subject
      continues to evolve. Rapid diagnostic tests have become more sensitive. Experts
      now consider not if but when they may replace throat cultures. Highly accurate
      rapid tests will still challenge clinicians to screen the right patients. The
      improvement of clinical diagnosis will require an understanding of the clinical
      spectrum of pharyngitis and questions relating to disease prevalence, test
      performance, and medical decision making. Implications for diagnostic strategies
      are discussed.

PMID- 15142481
TI  - Nebulization of Antibiotics in Management of Sinusitis.
AB  - Chronic sinusitis with recurrent acute infections continues to be a significant
      medical problem. Even after aggressive medical and surgical management, some
      patients continue to have recurrent infections. These infections are often
      multidrug-resistant. Topical delivery of medications into body cavities has been
      practiced for decades. Recently, the use of prescription antibiotic, antifungal,
      and anti-inflammatory topical medications has increased for sinus patients. This
      article examines emerging data on nebulized antimicrobials for patients with
      sinusitis.

PMID- 15142482
TI  - The Use of Ketolides in Treatment of Upper Respiratory Tract Infections.
AB  - Recent surveillance studies suggest that the incidence of resistance to macrolide
      antibiotics in common community-acquired respiratory tract pathogens,
      particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing
      and limiting the usefulness of these drugs. The ketolides, of which telithromycin
      is the first to be available for clinical use (but not yet in the United States),
      represent a new class of antibacterials developed specifically to combat
      respiratory tract pathogens that have acquired resistance to macrolides. The
      ketolides possess innovative structural modifications, a 3-keto group and a large
      N-substituted C11, C12-carbamate side chain. This novel structure allows
      ketolides, which are inhibitors of protein synthesis, to exert a more effective
      interaction with domain II of the 23S rRNA, enhancing binding to bacterial
      ribosomes and allowing binding to macrolide-lincosamide-streptogramin B-resistant
      ribosomes. This novel chemical structure also promotes greater stability of
      telithromycin in acid conditions, providing the potential for greater stability
      in gastric fluid and at cellular/tissue levels. Early clinical trials support the
      bacteriologic and clinical efficacy of telithromycin in the treatment of upper
      respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute
      sinusitis, including infections caused by macrolide-resistant S. pneumoniae and
      S. pyogenes. Common adverse side effects associated with telithromycin are
      predominantly gastrointestinal, usually of mild to moderate severity, and rarely
      involve withdrawal of the drug. Telithromycin represents an attractive option for
      the empiric treatment of upper RTIs, especially as resistance to macrolides is
      likely to continue to increase.

PMID- 15142484
TI  - Oseltamivir as Postexposure Prophylaxis for Influenza in Households.

PMID- 15142485
TI  - Clinical, Laboratory, and Radiologic Manifestation of SARS.
AB  - Severe acute respiratory syndrome (SARS) is a highly contagious and predominantly
      pneumonic illness caused by a novel coronavirus now commonly known as SARS-CoV.
      This article describes the key diagnostic clinical features, radiologic features,
      and investigation profiles of affected patients. We summarize our understanding
      from anecdotal experience and limited published data on the use of antiviral and
      corticosteroid therapy in the management of this highly contagious disease.

PMID- 15142483
TI  - Virologic Diagnosis, Viral Monitoring, and Treatment of Epstein-Barr Virus
      Infectious Mononucleosis.
AB  - Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is
      associated with severe infections in immunocompromised patients. EBV is also
      causally linked with several human malignancies. The heterophile antibody test
      and EBV-specific antibody tests remain the principal means of diagnosis of
      initial infection in otherwise healthy patients. Enzyme-linked immunosorbent
      assays have replaced the traditional immunofluorescence assays for EBV-specific
      antibodies. Several newer molecular diagnostic tests have become available that
      facilitate accurate monitoring of infection. The role of these tests for patients
      with uncomplicated infectious mononucleosis is limited, although these tests are
      being increasingly used to monitor the state and level of EBV replication for
      severe infections and among immunocompromised patients. Antiviral therapy has a
      limited, short-term effect on oropharyngeal shedding but has proven ineffective
      for the clinical manifestations of infectious mononucleosis. Patients with
      selected complications frequently benefit from short-term corticosteroid therapy.

PMID- 15142486
TI  - Transmission and Control of SARS.
AB  - Severe acute respiratory syndrome (SARS) was first recognized in China in
      November 2002 and was subsequently associated with a worldwide outbreak involving
      8098 people, 774 of whom died. The outbreak was declared contained on July 5,
      2003, after the last human chain of transmission of SARS had been broken. Whether
      outbreaks of SARS will return is debatable, but no one disagrees that it is
      important to be prepared for this possibility. This article presents an overview
      of the transmission and control of SARS based on the current state of knowledge
      derived from published studies of the outbreak and on our own personal
      experience.

PMID- 15142487
TI  - SARS in the Intensive Care Unit.
AB  - Approximately 20% of patients with severe acute respiratory syndrome (SARS)
      develop respiratory failure that requires admission to an intensive care unit
      (ICU). Old age, comorbidity, and elevated lactate dehydrogenase on hospital
      admission are associated with increased risk for ICU admission. ICU admission
      usually is late and occurs 8 to 10 days after symptom onset. Acute respiratory
      distress syndrome occurs in almost all admitted patients and most require
      mechanical ventilation. ICU admission is associated with significant morbidity,
      particularly an apparent increase in the incidence of barotrauma and nosocomial
      sepsis. Long-term mortality for patients admitted to the ICU ranges from 30% to
      50%. Many procedures in ICUs pose a high risk for transmission of SARS
      coronavirus to health care workers. Contact and airborne infection isolation
      precautions, in addition to standard precautions, should be applied when caring
      for patients with SARS. Ensuring staff safety is important to maintain staff
      morale and delivery of adequate services.

PMID- 15142488
TI  - Controlling Neuropathic Pain in HIV.
AB  - Neuropathic pain is associated with numerous systemic illnesses, including HIV
      infection. The diagnosis and management of peripheral neuropathy presents
      diagnostic and therapeutic challenges. Among various forms of HIV-associated
      peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most
      common. DSP may be caused or exacerbated by neurotoxic antiretrovirals,
      particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate
      pharmacologic intervention for peripheral neuropathy should be based on efficacy,
      safety, ease of administration, and cost. We review treatment options for painful
      HIV neuropathy, including experimental agents studied in recent and ongoing
      clinical trials.

PMID- 15142489
TI  - The Role of Baseline HIV-1 Resistance Testing in Patients with Established
      Infection.
AB  - Effective long-term treatment of HIV-1 infection is challenging because of
      several factors, including antiretroviral drug resistance. Antiretroviral
      resistance testing has short-term benefit for optimizing the choice of a rescue
      regimen after treatment failure. Resistance testing also is recommended before
      therapy in pregnancy and acute infection or recent seroconversion. The benefit of
      routine resistance testing before starting treatment for established infection is
      less clear. This report summarizes the accumulating evidence of persistence of
      resistant mutants after initial infection, detectability of resistant virus with
      standard assays before treatment of established infection, the potential adverse
      impact of this baseline resistance on effectiveness of therapy, and the
      increasing prevalence of resistance in treatment-naive patients. Taken together,
      these data suggest that pretreatment genotypic resistance testing also may be
      useful in patients with established infection. Although further study is needed,
      clinicians are now encouraged to routinely obtain pretreatment resistance
      testing.

PMID- 15142490
TI  - [Enterococci and resistances].

PMID- 15142491
TI  - [Enterococcus faecalis bacteremia].
AB  - OBJECTIVE: Analysis of Enterococcus faecalis bacteremia epidemiological,
      clinical, microbiological and prognostic characteristics. METHODS: Retrospective
      analysis of clinical records of patients with E. faecalis bacteremia throughout 7
      years (January 1995-December 2001). RESULTS: 95 episodes of bacteremia were
      documented, 83.2% with nosocomial origin, 85.3% associated to previous invasive
      procedures and 9.5% in neonates. 57.9% patients suffered an underlying disease
      and 41.1% had received previously broad-spectrum antibiotics without activity
      against enterococcus. 32.6% bacteremia episodes was considered primary and, in
      the rest, the most frequent associated sources of infection were cardiovascular,
      intra-abdominal, urogenital, and lung. The resistance study showed a single case
      of resistance to ampicillin and none to glucopeptides. Global mortality was
      23.9%, although only in 9.9% was directly attributable to bacteremia. Inadecuate
      treatment and mechanical ventilation were factors of poor prognosis in the
      multivariate analysis. CONCLUSIONS: E. faecalis bacteremia is in our environment
      essentially a hospital-acquired infection in patients with severe underlying
      diseases, subject to invasive procedures, and previously treated with wide
      spectrum antibiotherapy. Ampicillin continues to be the treatment of choice.
      Inappropriateness of the initial empirical antibiotic treatment and mechanical
      ventilation are factors of poor prognosis.

PMID- 15142492
TI  - [Colonic polyps: dysplasia predictive factors].
AB  - OBJECTIVE: Analyze the presence of dysplasia in colonoscopy visualized colonic
      polyps, and the predictive factors for high grade dysplasia. MATERIAL AND
      METHODS: We studied the polyps observed in the colonoscopies carried out during
      the year 2001. Colonoscopies carried out in 2,144 patients were analyzed, with
      demonstration of polyps in 326 patients (average age: 67 12,6 years, 63,5%
      males). 732 polyps were analyzed, with average of 2.27 2 polyps by patient.
      RESULTS: 72% polyps were located distally to splenic flexure, and sigmoid colon
      was the most frequent location (34.7%). Most of the polyps (86%) were sessile.
      Only 3% were > 2 cm, and the majority (88%) was < 1 cm. The most prevalent
      histological type was tubular adenoma (36%). Dysplasia was observed in 42.2% (low
      grade in 40% and high grade in 2.2%) Size > 1 cm and location proximal to splenic
      flexure were the only variables with indendent significant association to high
      grade dysplasia. CONCLUSIONS: The presence of high grade dysplasia in the colonic
      polyps was related in our cohort both to the location of the polyps in the colon
      and to its size, so that greater risk was for proximal polyps and for polyps > 1
      cm.

PMID- 15142493
TI  - [Early diabetic nephropathy and cardiovascular disease in a Mediterranean
      population: risk factors and treatment intensity].
AB  - The objective of this cross-sectional study was to evaluate the impact of early
      diabetic nephropathy on the presence of cardiovascular disease (CVD) in a
      Mediterranean population, as well as the prevalence in these patients of
      traditional cardiovascular risk factors and its treatment intensity in accordance
      with international recommendations. In 123 patients with type 2 diabetes and
      incipient nephropathy the presence of CVD, smoking, hypertension, dyslipemia, and
      their treatment was recorded. CVD prevalence was 34%. Age, nephropathy stage
      (micro/macroalbuminuria), and smoking were associated with the presence of CVD.
      Hypertension, dyslipemia, and smoking were present in 83%, 81%, and 59%,
      respectively. Coexistence of several risk factors was frequent and was associated
      with a higher incidence of CVD. 79% hypertensive patients and 43% dyslipemic
      patients received pharmacological treatment but only 17% and 9%, respectively,
      reached a good control of their disease. Patients with known CVD showed also a
      deficient control. Accordingly, early diabetic nephropathy induces a multiplier
      effect on the cardiovascular risk of a Mediterranean population. Higher
      prevalence and association with cardiovascular risk factors, with smoking in a
      predominant role, are associated with this higher risk. Despite this, the
      intensity of treatment and control of these risk factors is deficient, which
      means that a better and more intensive treatment should reduce the morbidity and
      mortality in these patients.

PMID- 15142494
TI  - [Tumor-associated significant pericardiac effusions: analysis of 18 cases].
AB  - Metastatic infiltration is most frequent than primary pericardiac tumors. Most
      frequent tumors are adenocarcinoma and lymphomas. A retrospective analysis of 18
      oncological patients with significant pericardiac effusion (SPE) is carried out.
      The conclusions of the study are: SPE can be the first manifestation of a
      neoplasm; frequently, pericardiac tamponade (PT) has a neoplastic origin; thorax
      is the most frequent localization of the primary tumor; pericardiac fluid (PF)
      cytology analysis has low diagnostic yield; most useful diagnostic tests are
      thoracocentesis, thorax computerized tomography (CT) and bronchoscopy; SPE in a
      neoplasm suggest poor short-term prognosis; poor prognosis variables in this
      series were primary tumor unfavorable histology, advanced tumor disease and
      (probably) presentation as PT.

PMID- 15142495
TI  - [Consumption of contaminated fish and nematodes intestinal parasitosis].

PMID- 15142497
TI  - [Current antiretroviral treatment].

PMID- 15142496
TI  - [Nodular thyroid pathology diagnostic approach].

PMID- 15142498
TI  - [Rheumatoid arthritis treatment].

PMID- 15142499
TI  - [Right suprammary indurated patch in an adolescent].

PMID- 15142500
TI  - [Lung embolism of cardiac origin].

PMID- 15142501
TI  - [Left hypochondrium mass after left rib cage accidental injury].

PMID- 15142502
TI  - [Coronary risk in patients infected by human immunodeficiency virus].

PMID- 15142503
TI  - [CA 19-9 tumor marker increase in a patient with lung adenocarcinoma].

PMID- 15142504
TI  - [Loffler, perhaps Loeffler, but never Loeffler].

PMID- 15142505
TI  - [Prevalence of maternal-fetal toxoplasmosis. A 15-year study (1987-2001)].

PMID- 15142506
TI  - [Renal involvement in the human immunodeficiency virus infection].
AB  - BACKGROUND AND OBJECTIVE: Although renal pathologies are becoming an emergent
      problem in the population infected by the human immunodeficiency virus (HIV),
      there is very scarce information about the natural course of this problem. The
      objective of the present study is to describe renal lesions in an autopsy series
      of HIV-infected patients never treated with antiretroviral therapies. PATIENTS
      AND METHOD: Autopsy information has been retrospectively retrieved from 61 HIV
      infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males)
      died in our hospital between 1984 and 1997. None of the patients received
      antiretroviral therapy. All autopsy and clinical reports were considered, as well
      as basic analytical parameters about renal function. Renal autopsy samples were
      specifically reviewed. RESULTS: At the time of the last admission, 9.8% of
      patients had renal insufficiency, who made up 44.3% of patients having renal
      insufficiency anytime. Infections were the main cause of death (76%). The
      majority of patients (93.4%) showed histopathological renal abnormalities, which
      were highly heterogeneous. Renal lesions were mainly located on the tubules
      (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7%
      of patients. Most frequent histopathological diagnosis was acute tubular necrosis
      (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial
      nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%).
      There were no significant differences when considering the existent of renal
      failure. CONCLUSIONS: Renal histological abnormalities are frequent in the
      natural evolution of HIV infection. There is an important heterogeneity of
      lesions, mainly involving tubules, interstitium and mesangium. The cause of renal
      lesions is predominantly septic, according to the chief systemic process. It does
      not exist any relationship between renal analytical parameters and the presence
      of renal damage.

PMID- 15142507
TI  - [Epidemiology of lipid profile of the Spanish elderly population: the EPICARDIAN
      study].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to describe the lipid
      profile, the levels of serum total cholesterol (TC), LDL cholesterol (C-LDL), HDL
      cholesterol (C-HDL) and triglyceride (TG), to compare these levels between
      geographical areas and to estimate the prevalence of dyslipidemia in elderly
      residents (65 years and older) from urban and rural areas of Spain. PATIENTS AND
      METHOD: Epidemiological, observational, multicentre study of Spanish elderly
      people residents (>or= 65 years old) of 3 communities in 3 Spanish regions:
      Arevalo (Avila) and Begonte (Lugo) as rural areas and Lista (Central Madrid) as
      urban area. Stratified randomized sample by age and sex from population census of
      each area. The participation rate was: 84.6%. At-home interviews (phase 1) (n =
      4522): with determination of capillary blood cholesterol levels (Reflotron) and
      clinical visit (phase 2) (1/3 selected randomly, n = 1907): determination of
      serum TC levels (enzymatic colorimetric method CHOP-PAD), C-HDL, C-LDL
      (Friedewald equation) and TG (Trinder Method). RESULTS: Mean concentrations of TC
      was 230.3 (46.8) mg/dl. These levels decreased significantly with increasing age
      (p < 0.001), higher in women (p = 0.001); lower in Lugo (226.4 [49.7] mg/dl) than
      in Madrid (233.2 [42.3] mg/dl) and Arevalo (236.5 [43] mg/dl) (p = 0.002). Global
      prevalence of hypercholesterolemia by SEA simplified criteria was: 68.9% (95%
      confidence interval, 66.8-71). Mean concentrations of C-LDL was: 159.4 (37.9)
      mg/dl; C-HDL: 48.2 (15) mg/dl, and TG: 119.7 (63.85) mg/dl. 31% of cases were
      awarded about the hypercholesterolemia. Only 30% of them were under treatment
      with lipid lowering drugs; and 30% of the subjects showed CT concentrations < 200
      mg/dl, with no differences by sex, age, study area or education level. Female
      sex, urban habitat and hypertension were the only variables independently
      associated to hypercholesterolemia in the logistic model. CONCLUSIONS: The
      prevalence of dyslipidemia is slightly higher to SEA estimation for the European
      elderly population (50%), greater in women and in younger groups. The awareness,
      treatment and control of hypercholesterolemia are low among the Spanish elderly
      population.

PMID- 15142508
TI  - [Meta-analysis on safety and efficacy of liposomal amphotericin B in the
      empirical treatment of febrile neutropenia].
AB  - BACKGROUND AND OBJECTIVE: We compared the safety and efficacy of liposomal
      amphotericin B with other formulations of amphotericin B and voriconazol as an
      empirical treatment of febrile neutropenia. MATERIAL AND METHOD: Several
      randomized controlled clinical trials, designed to evaluate the safety and/or
      efficacy of liposomal amphotericin B in the empirical treatment of febrile
      neutropenia, in comparison with other amphotericin B formulations or voriconazol,
      were identified by means of a search in MEDLINE, EMBASE and Cochrane Controlled
      Trials Register's data bases. American Society of Microbiology and American
      Society of Clinical Oncology abstracts, presented between 1999 and 2002, were
      also included in the search. Prior to data extraction, concepts like
      nephrotoxicity, infusion-related adverse events and efficacy (success rate and
      mortality) were defined. RESULTS: Two studies comparing liposomal amphotericin B
      with conventional amphotericin B, one comparing liposomal amphotericin B with
      amphotericin B lipid complex and one comparing liposomal amphotericin B with
      voriconazol were included in the analysis. Patients treated with liposomal
      amphotericin B had lower nephrotoxicity than patients treated with other
      amphotericin B formulations or with conventional amphotericin B (RR = 0.49);
      conversely, no statistically significant differences with regard to voriconazol
      were observed. In terms of efficacy, mortality rate and therapeutic failure,
      patients treated with limposomal amphotericin B showed a slightly higher
      efficacy. CONCLUSIONS: Liposomal amphotericin B is a lipidic formulation with a
      slightly higher efficacy than other amphotericin B formulations and voriconazol.
      In terms of nephrotoxicity, liposomal amphotericin B showed lower nephrotoxicity
      than other amphotericines while its safety rates were similar to those of
      voriconazol.

PMID- 15142509
TI  - [Genotypic resistance to sulfamide drugs among patients with Pneumocystis
      jiroveci pneumonia].
AB  - BACKGROUND AND OBJECTIVE: The absence of culture methods to recognize the
      presence of resistance to sulfa or sulfone drugs in Pneumocystis jiroveci has led
      to develop molecular techniques based on the identification of mutations in the
      dihydropteroate synthase gene (DHPS). The aim of this study was to determine the
      frequency of these mutations in our geographical area, since in Spain there is no
      information concerning this issue. PATIENTS AND METHOD: The study included all
      Pneumocystis pneumonia cases identified in our hospital during two years.
      Diagnosis was made by nested PCR in bronchoalveolar lavage samples. DHPS-3 and
      DHPS-4 primers were used to amplify the DHPS gene and mutations associated with
      sulfa resistance were identified using a restriction fragment length polymorphism
      assay. RESULTS: In 9 out of the 12 cases identified, DHPS could be amplified
      (75%) from which 3 (33.3%) showed some mutation linked to sulfa resistance.
      CONCLUSIONS: In our area, we have found a relatively high frequency of pneumonia
      caused by P. jiroveci's strains with mutations associated with sulfa resistance.

PMID- 15142510
TI  - [Advanced age, lipoproteic profile and cardiovascular risk].

PMID- 15142511
TI  - [Current medicine: lights and shadows].

PMID- 15142512
TI  - [Evaluation of drug addicts with associated pathology. Clinical and therapeutic
      aspects of the integral attention].
AB  - We review the evaluation and treatment of patients with drug addictions
      complicated by other acute or chronic diseases from the perspective of the
      hospital setting. The spectrum of drug addiction's complications is broad and in
      many instances it is predetermined by the abuse substance and its administration
      route. Some complications of intravenous drug addiction have dramatically
      decreased in the last few years as a result of a better knowledge of hygienic
      customs and after the implementation of some health interventions such as the
      provision of sterile injectable devices. Two highly prevalent infections -
      HIV/AIDS and hepatitis C-- remain from the period in which most HIV infections
      owed to the intravenous use of heroin. Of note, these two infections largely
      account for the survival and quality of life of those who quit their addiction.
      On the other hand, it is still common the hospitalization of patients with both
      alcohol dependence and intercurrent diseases in whom their drug addiction may
      pass unnoticed. Other common situations include the treatment of acute patients
      with cocaine addiction and psychiatric comorbidity, patients under methadone
      therapy and, in general, all those cases in which, in emergency, ordinary
      hospital wards and specialized units, a wide differential diagnosis is raised
      when there is a coexistence of signs and symptoms common to an addiction,
      infection and/or intoxication. An integral vision of drug addiction and its
      complications, as well as the clinical evaluation of all health problems, is
      fundamental for the prognosis and treatment of these patients.

PMID- 15142513
TI  - [Cutaneous infection by Mycobacterium chelonae after treatment with acupunture].

PMID- 15142515
TI  - [Chronic venous insufficiency as an onset form of a traumatic arteriovenous
      fistula].

PMID- 15142514
TI  - [Pericardial effusion associated with interferon therapy].

PMID- 15142516
TI  - [Murine tifus in Canary Islands, Spain].

PMID- 15142517
TI  - [Cushing syndrome secondary to megestrol acetate in a patient with AIDS].

PMID- 15142518
TI  - [Acute myeloid leukemia with MOZ/CBP rearrangement].

PMID- 15142519
TI  - Acquiring maternal immunoglobulin; different receptors, similar functions.
AB  - The isolation of a novel Fc receptor (FcRY) from chicken yolk sac provides
      insight at the mechanistic level as to how avian maternal immunoglobulin (IgY) is
      transferred to offspring. This receptor is distinct from its mammalian
      counterpart and is a phospholipase A(2) receptor homolog. Biophysical analyses
      indicate that FcRY achieves pH-dependent binding to IgY through a conformational
      change.

PMID- 15142520
TI  - Back to central tolerance.
AB  - The establishment and maintenance of immunological tolerance entails both central
      and peripheral mechanisms. The latter have been highlighted in the past several
      years, mostly because of great interest in the activities of regulatory T cells.
      However, an important role for central tolerance mechanisms has been reemphasized
      by recent results on human autoimmune diseases, including APECED and type 1
      diabetes.

PMID- 15142521
TI  - Pathogenic roles of B cells in human autoimmunity; insights from the clinic.
AB  - The pathogenic roles of B cells in human autoimmune diseases involve a multitude
      of mechanistic pathways and include the well-established contributions of
      autoantibodies and immune complexes that induce local inflammatory reactions and
      tissue destruction. Recent results using several novel B cell-directed therapies
      have provided new insights into additional roles of B cells in human
      autoimmunity. In this review, we will highlight some of these studies and discuss
      how clinical insights parallel murine models of normal immunity and autoimmunity.

PMID- 15142522
TI  - The roles of the new negative T cell costimulatory pathways in regulating
      autoimmunity.
AB  - The B7 family of T cell costimulatory molecules has recently acquired several new
      members. Some of these are activating while others are inhibitory. In this
      review, we will focus on the novel inhibitory pathways with particular emphasis
      on the PD-1:PD-L pathway. Understanding the mechanisms of these pathways has
      implications for development of novel treatment strategies for autoimmune
      disease, transplantation, tumor immunotherapy, and vaccine development.

PMID- 15142523
TI  - Autoimmunity through cytokine-induced dendritic cell activation.
AB  - We propose a model where autoimmunity can be viewed as a dynamic system driven by
      opposite vectors IFN-alpha/beta and TNF. These cytokines drive differentiation of
      distinct types of DCs, TNF-DCs, or IFN-DCs, which present different antigens
      leading to distinct autoimmune responses. When balanced, both cytokines synergize
      in protective immunity. When one of the cytokines prevails, autoimmunity occurs,
      Type I interferons (IFN-alpha/beta) playing a major role in systemic lupus
      erythematosus (SLE) and TNF playing a major role in rheumatoid arthritis. This
      model complements the Type 1/Type 2 paradigm. Therefore, immunity can be viewed
      as a dynamic system driven by two sets of opposite vectors: IFN-alpha/beta/TNF
      and IFN-gamma/IL-4.

PMID- 15142524
TI  - Dynamics of blood-borne CD8 memory T cell migration in vivo.
AB  - Memory T cells are distributed throughout the body following infection, but the
      migratory dynamics of the memory pool in vivo is unknown. The ability of
      circulating microbe-specific memory T cells to populate lymphoid and nonlymphoid
      tissues was examined using adoptive transfer and parabiosis systems. While
      migration of memory CD8 T cells to lymph nodes and peritoneal cavity required
      G(i)-coupled receptor signaling, migration to the spleen, bone marrow, lung, and
      liver was independent of this pathway. Following parabiosis, memory T cells
      rapidly equilibrated into the lymphoid tissues, lung, and liver of each
      parabiont, implying most memory cells were not obligately tissue resident.
      Equilibration of memory cell populations was delayed in the brain, peritoneal
      cavity, and intestinal lamina propria, indicating controlled gating for entry
      into these tissues. In addition, memory cell migration to the lamina propria
      required beta7 integrins. Thus, the blood-borne T cell pool serves to maintain
      the homeostasis of tissue-based memory populations.

PMID- 15142525
TI  - An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding
      domain signals negatively in T cells.
AB  - Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in
      downregulating T cell responses. A number of autoimmune diseases have shown
      genetic linkage to the CTLA-4 locus. We have cloned and expressed an
      alternatively spliced form of CTLA-4 that has genetic linkage with type I
      diabetes in the NOD mice. This splice variant of CTLA-4, named ligand-independent
      CTLA-4 (liCTLA-4), lacks exon2 including the MYPPPY motif essential for binding
      to the costimulatory ligands B7-1 and B7-2. Here we show that liCTLA-4 is
      expressed as a protein in primary T cells and strongly inhibits T cell responses
      by binding and dephosphorylating the TcRzeta chain. Expression of liCTLA-4, but
      not full-length CTLA-4 (flCTLA-4), was higher in memory/regulatory T cells from
      diabetes-resistant NOD congenic mice compared to susceptible NOD mice. These data
      suggest that increased expression and negative signaling delivered by the liCTLA
      4 may regulate development of T cell-mediated autoimmune diseases.

PMID- 15142526
TI  - Activation-induced polarized recycling targets T cell antigen receptors to the
      immunological synapse; involvement of SNARE complexes.
AB  - The mechanism by which T cell antigen receptors (TCR) accumulate at the
      immunological synapse has not been fully elucidated. Since TCRs are continuously
      internalized and recycled back to the cell surface, we investigated the role of
      polarized recycling in TCR targeting to the immunological synapse. We show here
      that the recycling endosomal compartment of T cells encountering activatory
      antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site.
      Moreover, TCRs in transit through recycling endosomes are targeted to the
      immunological synapse. Inhibition of T cell polarity, constitutive TCR
      endocytosis, or recycling reduces TCR accumulation at the immunological synapse.
      Conversely, increasing the amount of TCRs in recycling endosomes before synapse
      formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs
      from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR
      accumulation at the immunological synapse, indicating that vesicle fusion
      mediated by SNARE complexes is involved in TCR targeting to the immunological
      synapse.

PMID- 15142527
TI  - LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by
      facilitating B cell adhesion and synapse formation.
AB  - The integrin LFA-1 and its ligand ICAM-1 mediate B cell adhesion, but their role
      in membrane-bound antigen recognition is still unknown. Here, using planar lipid
      bilayers and cells expressing ICAM-1 fused to green fluorescence protein, we
      found that the engagement of B cell receptor (BCR) promotes B cell adhesion by an
      LFA-1-mediated mechanism. LFA-1 is recruited to form a mature B cell synapse
      segregating into a ring around the BCR. This distribution is maintained over a
      wide range of BCR/antigen affinities (10(6) M(-1) to 10(11) M(-1)). Furthermore,
      the LFA-1 binding to ICAM-1 reduces the level of antigen required to form the
      synapse and trigger a B cell. Thus, LFA-1/ICAM-1 interaction lowers the threshold
      for B cell activation by promoting B cell adhesion and synapse formation.

PMID- 15142528
TI  - The chicken yolk sac IgY receptor, a functional equivalent of the mammalian MHC
      related Fc receptor, is a phospholipase A2 receptor homolog.
AB  - In mammals, IgG is transferred from mother to young by the MHC-related receptor
      FcRn, which binds IgG in acidic endosomes and releases it at basic pH into blood.
      Maternal IgY, the avian counterpart of IgG, is transferred to embryos across yolk
      sac membranes. We affinity-purified the chicken yolk sac IgY receptor (FcRY) and
      sequenced its gene. FcRY is unrelated to MHC molecules but is a homolog of the
      mammalian phospholipase A(2) receptor. Analytical ultracentrifugation and
      truncation experiments suggest that FcRY forms a compact structure containing an
      IgY binding site at acidic pH but undergoes a conformational change at basic pH
      that disrupts the site. FcRY is thus unrelated to mammalian FcRn in both its
      structure and mechanism for pH-dependent binding, illustrating distinct routes
      utilized by evolution to transfer antibodies.

PMID- 15142529
TI  - Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T
      cell responses by Notch/RBP-J signaling.
AB  - RBP-J is a key mediator of Notch signaling that regulates a large spectrum of
      cell fate determinations. To elucidate the functions of Notch signaling in T cell
      development, we inactivated RBP-J specifically at two stages of T cell
      development by crossing RBP-J floxed mice with lck-cre or CD4-cre transgenic
      mice. The loss of RBP-J at an earlier developmental stage resulted in enhanced
      generation and accelerated emigration of gammadelta T cells, whereas alphabeta T
      cell development was arrested at the double-negative 3 stage. The loss of RBP-J
      at a later stage did not affect the absolute number or the production rate of CD4
      or CD8-positive mature T cells but enhanced Th1 cell response and reduced CD4(+)
      T cell proliferation. Our data demonstrated that Notch/RBP-J signaling regulates
      gammadelta T cell generation and migration, alphabeta T cell maturation, terminal
      differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells.

PMID- 15142530
TI  - Alternative macrophage activation is essential for survival during
      schistosomiasis and downmodulates T helper 1 responses and immunopathology.
AB  - Macrophage/neutrophil-specific IL-4 receptor alpha-deficient mice (LysM(Cre)IL
      4Ralpha(-/flox)) were generated to understand the role of IL-4/IL-13 responsive
      myeloid cells during Type 2 immune responses. LysM(Cre)IL-4Ralpha(-/flox) mice
      developed protective immunity against Nippostrongylus brasiliensis accompanied by
      T(H)2 development and goblet cell hyperplasia. In contrast, LysM(Cre)IL-4Ralpha(
      /flox) mice were extremely susceptible to Schistosoma mansoni infection with 100%
      mortality during acute infection. Mortality was not dependent on neutrophils and
      occurred in the presence of T(H)2/Type 2 responses, granuloma formation, and egg
      induced fibrosis. Death was associated with increased T(H)1 cytokines, hepatic
      and intestinal histopathology, increased NOS-2 activity, impaired egg expulsion,
      and sepsis. IL-10 was not able to compensate for the absence of IL-4/IL-13
      activated alternative macrophages. Together, this shows that alternative
      macrophages are essential during schistosomiasis for protection against organ
      injury through downregulation of egg-induced inflammation.

PMID- 15142531
TI  - Monomeric and polymeric gram-negative peptidoglycan but not purified LPS
      stimulate the Drosophila IMD pathway.
AB  - Insects depend solely upon innate immune responses to survive infection. These
      responses include the activation of extracellular protease cascades, leading to
      melanization and clotting, and intracellular signal transduction pathways
      inducing antimicrobial peptide gene expression. In Drosophila, the IMD pathway is
      required for antimicrobial gene expression in response to gram-negative bacteria.
      The exact molecular component(s) from these bacteria that activate the IMD
      pathway remain controversial. We found that highly purified LPS did not stimulate
      the IMD pathway. However, lipid A, the active portion of LPS in mammals,
      activated melanization in the silkworm Bombyx morii. On the other hand, the IMD
      pathway was remarkably sensitive to polymeric and monomeric gram-negative
      peptidoglycan. Recognition of peptidoglycan required the stem-peptide sequence
      specific to gram-negative peptidoglycan and the receptor PGRP-LC. Recognition of
      monomeric and polymeric peptidoglycan required different PGRP-LC splice isoforms,
      while lipid A recognition required an unidentified soluble factor in the
      hemolymph of Bombyx morii.

PMID- 15142532
TI  - Characterization of oligosaccharides in milk of bearded seal (Erignathus
      barbatus).
AB  - Carbohydrates were extracted from milk of a bearded seal, Erignathus barbatus
      (Family Phocidae). Free neutral oligosaccharides were separated by gel
      filtration, anion-exchange chromatography and preparative thin layer
      chromatography, while free acidic oligosaccharides were separated by gel
      filtration and then purified by ion exchange chromatography, gel filtration and
      high performance liquid chromatography. Oligosaccharide structures were
      determined by 1H-NMR spectroscopy. The structures of the neutral oligosaccharides
      were as follows; lactose, 2'-fucosyllactose, lacto-N-fucopentaose IV, difucosyl
      lacto-N-neohexaose and difucosyl decasaccharide which contained a lacto-N
      neohexaose unit as well as an additional Gal(beta1-4)GlcNAc(beta1-3) unit and two
      residues of non-reducing Fuc(alpha1-2). The acidic oligosaccharides were thought
      to contain an Neu5Ac(alpha2-6) residue linked to GlcNAc or a sulfate linked to
      Gal at OH-3. The sialyl oligosaccharides and sulfated oligosaccharides had a
      lacto-N-neohexaose unit and two non-reducing Fuc(alpha1-2) residues and some of
      them had in addition one or two Gal(beta1-4)GlcNAc(beta1-3) units. The milk
      oligosaccharides of the bearded seal were compared to those of the harbour seal,
      which had been studied previously.

PMID- 15142533
TI  - Somatostatin-, calcitonin gene-related peptide, and gamma-aminobutyric acid-like
      immunoreactivitity in the frog lumbosacral spinal cord: distribution and effects
      of sciatic nerve transection.
AB  - Using immunohistochemistry and optical densitometry, somatostatin (SOM),
      calcitonin gene-related peptide (CGRP), and gamma-aminobutyric acid (GABA) were
      investigated in the lumbosacral spinal cord of the frog Rana catesbeiana after
      sciatic nerve transection. In control animals, the densest network of the SOM-,
      CGRP- and GABA-like immunoreactive fibers was located in the dorsal part of the
      lateral funiculus. SOM and GABA-like fibers were found in the dorsal terminal
      field and in the mediolateral band. The latter region showed CGRP and SOM-like
      immunoreactive cell bodies. SOM- and GABA-like immunoreactive neurons also
      occurred around the cavity of the central canal, and other GABA-like fibers were
      found in the ventral terminal field. While the ventral horn showed scarce
      somatostatin-like fibers, the putative motoneurons were immunoreactive for the
      two peptides investigated and GABA, but only a few SOM- and GABA-like fibers
      occurred in the ventral funiculus. After axotomy, GABA-like immunoreactivity
      decreased in the dorsal part of the lateral funiculus on the same side of the
      lesion. The other regions remained labeled. These changes were observed at 3 days
      following axonal injury and persisted at 5, 8 and 15 days. There was no
      significant difference in the pattern of CGRP- and SOM- immunoreactivity between
      the axotomized and the control sides. These results are discussed in relation to
      the effects of the peripheral axotomy on GABA, SOM, and CGRP expression in
      vertebrates, emphasizing the use of frogs as a model to study the effects of
      peripheral nerve injury.

PMID- 15142535
TI  - Effects of fungal food quality and starvation on the fatty acid composition of
      Protaphorura fimata (Collembola).
AB  - The lipid pattern of animals is influenced by species, life stage, environmental
      conditions and diet. We investigated the effects of food quality and starvation
      on the phospholipid (PLFA) and neutral lipid (NLFA) fatty acid pattern of the
      collembolan Protaphorura fimata. Collembolans were fed with two common soil
      fungi, Agrocybe gibberosa and Chaetomium globosum, of which the cellular lipid
      composition was analysed. A. gibberosa was grown on agar with different nitrogen
      contents, resulting in altered fatty acid patterns and C:N ratios, i.e. fungi of
      different food quality. Collembolans did not mirror the lipid composition of the
      fungal diet as the pattern of major NLFAs in P. fimata was vice versa.
      Presumably, altered food quality of fungi caused compensatory responses by the
      collembolans, thereby diminishing the fungal signal. In a further experiment P.
      fimata (previously maintained with C. globosum) was kept without food for up to 4
      weeks. Starvation resulted in a decline in the total amount of NLFAs; however, it
      did not affect the fatty acid pattern, indicating that NLFAs were degraded
      indiscriminately. Generally, the PLFA profile of the collembolans changed only
      slightly due to variations in diet quality or starvation.

PMID- 15142534
TI  - Carotenoid and lipid content in muscle of Atlantic salmon, Salmo salar,
      transferred to seawater as 0+ or 1+ smolts.
AB  - Accumulation of lipids and carotenoids, including 4'-hydroxyechinenone (4'
      hydroxy-beta,beta-carotene-4-one), growth and condition factor were investigated
      in Atlantic salmon (Salmo salar) transferred to seawater as 0+ and 1+ smolts.
      Salmon were fed a diet with 30 mg/kg astaxanthin (3,3'-dihydroxy-beta,beta
      carotene-4,4'-dione) and 30 mg/kg canthaxanthin (beta,beta-carotene-4,4'-dione)
      for 35 weeks. The 0+ smolt contained more carotenoids than the 1+ smolt when mass
      differences were corrected for (P<0.0001), a difference also reflected by the
      tristimulus colour measurements (C1E a*- and b*-values). Astaxanthin and
      canthaxanthin comprised more than 93% of the total carotenoids, but small
      differences were observed in carotenoid composition. The condition factor was
      significantly higher in 0+ than 1+ smolts after correction for mass differences
      (P<0.01). There was a high correlation between ln-transformed muscle lipid (%)
      and ln-transformed body mass for 0+(R2=0.94) and 1+smolts (R2=0.97). The
      canthaxanthin metabolite 4'-hydroxyechinenone was isolated from muscle of
      Atlantic salmon fed a diet supplemented with canthaxanthin. It was characterised
      and identified by its absorption maximum (lambda(max)=458 nm in n-hexane), mass
      spectrometry (M+=566) and co-chromatography with authentic standard obtained by
      NaBH4-reduction of canthaxanthin on thin-layer chromatography and HPLC. HPLC of
      the camphanates of 4'-hydroxyechinenone revealed a stereoselective transformation
      in favour of the (4'S)-isomer, the (4'S) and (4'R)-isomers comprising
      approximately 81 and 19% of the total 4'-hydroxyechinenone, respectively. The
      percentage of 4'-hydroxyechineone of total carotenoids ranged from 1.3 to 3.1%
      and declined with fish size (P<0.001). We conclude that effects of time of
      seawater transfer of Atlantic salmon smolts have significant effect on carotenoid
      accumulation and other quality traits. The detailed biochemical and physiological
      basis for these differences require further elucidation.

PMID- 15142536
TI  - Two novel muramidases from skin mucosa of rainbow trout (Oncorhynchus mykiss).
AB  - Two novel antibacterial muramidases were purified to homogeneity from skin
      exudates of rainbow trout (Oncorhynchus mykiss). Unusually, one has an acidic
      isoelectric point and it is the first anionic muramidase to be reported for fish.
      Its molecular mass is 14,268 Da, as determined by mass spectrometry. The other
      muramidase is cationic with a mass of 14,252 Da. Partial N-terminal amino acid
      sequencing and peptide mapping strongly point to it being a c-type lysozyme, the
      first to be purified and characterised from skin of a salmonid. Its optimum pH
      ranges from 4.5 to 5.5 and its optimum temperature, at pH 5.0, is 33-49 degrees
      C, although it still exhibits activity at 5 degrees C. It is strongly
      bactericidal to the Gram-(+) bacterium Planococcus citreus, with a minimum
      bactericidal concentration of 100 U ml(-1), but is neither chitinolytic nor
      haemolytic. These two muramidases probably contribute to epithelial defence of
      the fish against microbes, either alone or in synergism with antibacterial
      peptides.

PMID- 15142537
TI  - Sterols of marine microalgae Pyramimonas cf. cordata (Prasinophyta), Attheya
      ussurensis sp. nov. (Bacillariophyta) and a spring diatom bloom from Lake Baikal.
AB  - The free sterol compositions of two marine microalgal species Pyramimonas cf.
      cordata (Prasinophyta), Attheya ussurensis sp. nov. (Bacillariophyta), and diatom
      bloom samples from Lake Baikal were determined by gas chromatography, gas
      chromatography-mass spectrometry and (for some sterol constituents) using nuclear
      magnetic resonance spectra. A variety of sterol profiles were found. The
      principal sterol in the prasinophyte P. cf. cordata, collected in the Sea of
      Japan near Vladivostok, was 24(R)-ethylcholesta-5,22E-dien-3beta-ol
      (poriferasterol), but not 24-ethyl-5,24(28)Z-dien-3beta-ol, as reported earlier
      in the related species Pyramimonas cordata. The principal sterol in the marine
      diatom A. ussurensis sp. nov. was identified as 24-ethylcholest-5-en-3beta-ol.
      The sample of diatom bloom caused by Stephanodiscus meyerii with admixtures of
      several other diatom species, contained cholesterol and 24-methylcholesta
      5,24(28)-dien-3beta-ol as main sterol constituents.

PMID- 15142538
TI  - Effect of glutamate on basal steroidogenesis by ovarian follicles of rainbow
      trout (Oncorhynchus mykiss).
AB  - The effects of glutamate on the in vitro basal steroid production of three
      maturational stages of rainbow trout (Oncorhynchus mykiss) ovarian follicles were
      investigated. Radioimmunoassays were used to measure the rates of synthesis of
      testosterone (T) and 17-estradiol (E2). High performance liquid chromatography
      (HPLC) was used to examine the steroid metabolites produced from a tritium
      labeled precursor, pregnenolone (P5). The glutamate agonist, N-methyl-d,l
      aspartate (NMA) had a dose-dependent suppressive effect on T and E2 synthesis in
      mid-vitellogenic (MV) follicles, but had no significant effect on early- (EV) and
      late-vitellogenic (LV) follicles. l-glutamic acid (GA) had a dose-related
      suppressive effect on T synthesis by MV follicles, suppressing both T and E2
      synthesis by LV follicles, but having no effect on EV follicles. HPLC separation
      of the steroid metabolites synthesized from P5 showed clear evidence of
      differences in rates of overall steroidogenesis of the three follicular stages,
      but no effect of either NMA or GA on the nature or the amount of the metabolites
      produced by the three developmental stages examined. The findings suggest that
      glutamate may act via a reduction in the production of P5, which is the principal
      rate-limiting step in the steroidogenic cascade, and not via modulation of
      steroidogenic enzyme activities.

PMID- 15142539
TI  - A novel 8.7 kDa protease inhibitor from chan seeds (Hyptis suaveolens L.)
      inhibits proteases from the larger grain borer Prostephanus truncatus
      (Coleoptera: Bostrichidae).
AB  - A novel trypsin inhibitor purified from chan seeds (Hyptis suaveolens, Lamiaceae)
      was purified and characterized. Its apparent molecular mass was 8700 Da with an
      isoelectric point of 3.4. Its N-terminal sequence showed a high content of acidic
      amino acids (seven out of 18 residues). Its inhibitory activity was potent toward
      all trypsin-like proteases extracted from the gut of the insect Prostephanus
      truncatus (Coleoptera: Bostrichidae), a very important pest of maize. This
      activity was highly specific, because among proteases from seven different
      insects, only those from P. truncatus and Manduca sexta (Lepidoptera: Sphingidae)
      were inhibited. This inhibitor has potential to enhance the defense mechanism of
      maize against the attack of P. truncatus.

PMID- 15142540
TI  - Lipid and fatty acid composition of muscle and liver from wild and captive mature
      female broodstocks of white seabream, Diplodus sargus.
AB  - Total lipids (TL), lipid classes, and their associated fatty acids from muscle
      and liver of captive and wild mature female broodstocks were investigated in
      order to estimate the fatty acid requirements of white seabream (Diplodus
      sargus). The results showed that the percentage of triacylglycerol was higher in
      liver and muscle of captive fish than in wild fish. The distribution of
      phospholipid classes in liver and muscle of both fish groups was similar,
      phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol being the
      predominant lipid classes. The general pattern of fatty acid distribution in
      total lipid of liver and muscle from captive and wild fish was similar. However,
      the relative percentage of specific fatty acids differed in captive and wild
      fish. The most noteworthy difference was the lower proportion of arachidonic acid
      (20:4n-6, AA) and the higher proportion of eicosapentaenoic acid (20:5n-3, EPA)
      in liver and muscle of captive fish with respect to those of wild fish. The
      proportion of docosahexaenoic acid (22:6n-3, DHA) did not differ between the two
      fish groups. The differences in EPA and AA proportions between captive and wild
      fish implied that captive fish presented a higher EPA/AA ratio and a lower
      DHA/EPA ratio than wild fish. In general terms, in both liver and muscle, the
      differences in fatty acid composition observed for TL were extended to all lipid
      classes. The results suggest that the different AA, EPA and DHA proportions in
      liver and muscle between captive and wild broodstocks are attributed to different
      levels of these fatty acids in broodstock diets.

PMID- 15142541
TI  - Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles.
AB  - A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were
      synthesized and evaluated for their activity against kinetoplastid parasites.
      Formation of the oxadiazole ring was accomplished through the reaction of
      benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by
      reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The
      thiocyanate-containing compounds possessed low micromolar activity against
      Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were
      less active against these parasites. 3-(4-Chlorophenyl)-5-(thiocyanatomethyl)
      1,2,4-oxadiazole (compound 4b) displayed modest selectivity for L. donovani
      axenic amastigote-like parasites over J774 macrophages, PC3 prostate cancer
      cells, and Vero cells (6.4-fold, 3.8-fold, and 9.1-fold, respectively), while 3
      (3,4-dichlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4 h) showed
      30-fold selectivity against Vero cells but was not selective against PC3 cells.
      In a murine model of visceral leishmaniasis, compound 4b decreased liver
      parasitemia caused by L. donovani by 48% when given in five daily i.v. doses at
      5mg/kg and by 61% when administered orally for 5 days at 50 mg/kg. These results
      indicate that aromatic thiocyanates hold promise for the treatment of leishmanial
      infections if the selectivity of these compounds can be improved.

PMID- 15142542
TI  - Design, synthesis, and biological activity of novel 4-(3,4-dimethoxyphenyl)-2
      methylthiazole-5-carboxylic acid derivatives.
AB  - Novel 4-(3,4-dimethoxyphenyl)-2-methylthiazole-5-carboxylic acid derivatives (11
      23) were synthesized from 3,4-dimethoxyacetophenone (5) in six-step procedure.
      Their biological activities were evaluated in the greenhouse. Some of the
      compounds had shown fungicidal and insecticidal activities at 375 g ai/ha and 600
      g ai/ha, respectively.

PMID- 15142543
TI  - Design and synthesis of novel hydrophilic spacers for the reduction of
      nonspecific binding proteins on affinity resins.
AB  - Tubulin and actin often bind nonspecifically to affinity chromatography resins,
      complicating research toward identifying the cellular targets. Reduction of
      nonspecific binding proteins is important for success in finding such targets. We
      herein disclose the design, synthesis, and effectiveness in reduction of
      nonspecific binding proteins, of novel hydrophilic spacers (2-5), which were
      introduced between matrices and a ligand. Among them, tartaric acid derivative
      (5) exhibited the most effective reduction of nonspecific binding proteins,
      whilst maintaining binding of the target protein. Introduction of 5 on TOYOPEARL
      reduced tubulin and actin by almost 65% and 90% compared to that without the
      hydrophilic spacer, respectively, with effective binding to the target protein,
      FKBP12.

PMID- 15142544
TI  - Hexofuranosyl thymidines inserted into oligodeoxynucleotides via their two
      exocyclic hydroxy groups. Oligo synthesis and RNase H activity.
AB  - Hexofuranosyl nucleosides are considered as conformationally restricted acyclic
      nucleosides using a furanose ring to link the diol backbone to the nucleobase.
      The phosphoramidite of 1-(2,3-dideoxy-beta-D-erythro-hexofuranosyl)thymine was
      synthesized from thymidine with formation of a new stereocentre at C-5' and the
      nucleoside was used in oligodeoxynucleotide (ODN) synthesis. Binding of mixed
      sequence ODNs towards complementary DNA and RNA showed decreased affinity
      compared to the wild-type oligos. Insertion in the middle of poly alphaT sequence
      led to stabilization of ODN/dA(14) duplexes at low ionic strength, but a decrease
      was observed in medium and high salt buffers compared to d(alphaT)(14)/dA(14).
      Both beta and alpha hexofuranosyl thymidines allowed cleavage of complementary
      mixed-sequence RNA by RNase H to the 3'-site of the modification in ODNs whereas
      a limited inhibition was detected from the 5'-site.

PMID- 15142545
TI  - Design and synthesis of chromogenic thiopeptolide substrates as MetAPs active
      site probes.
AB  - Twenty one chromogenic thiopeptolide substrates were designed and synthesized as
      the active site probes and analyzed with each S1 site of mutant residues and
      enzymes of wild-type MetAP1s. The preliminary enzymatic experiments indicate that
      cysteine 70 or 202, at either Escherichia coli or human MetAP1, played a crucial
      role in the methionine hydrolysis.

PMID- 15142546
TI  - Enantioselective synthesis of (+)-8-hydroxy-8-methylidarubicinone.
AB  - An asymmetric Diels-Alder reaction methodology was employed to construct the
      tetracyclic structure of the anthracyclinone. A five-step sequence was needed to
      furnish the target (+)-8-hydroxy-8-methylidarubicinone.

PMID- 15142547
TI  - Synthesis, molecular modeling, and evaluation of nonphenolic indole analogs of
      mycophenolic acid.
AB  - Based on the promising activity of an indole-3-carboxamide derivative, a
      nonphenolic analog of mycophenolic acid (MPA), we report herein the synthesis of
      a compound containing two important features for the activity of MPA, the ring
      methoxy and methyl. The synthesis was accomplished using two strategies; a method
      dependent on stepwise building of the hexenoate side chain followed by the
      indolecarboxamide ring system, and a convergent route that depended on 1,3
      sigmatropic rearrangement as a key step. Docking experiments on both Chinese
      Hamster and Human Type-II inosine monophosphate dehydrogenase (IMPDH) showed that
      this compound has potential binding interactions with the NAD site. The analogs
      showed no activity against MCF7-S, MCF7-R, or IGR-OV1 cancer cells.

PMID- 15142548
TI  - Platelet aggregation and antibacterial effects of an l-amino acid oxidase
      purified from Bothrops alternatus snake venom.
AB  - The isolation and biochemical/enzymatic characterization of an L-amino acid
      oxidase, Balt-LAAO-I, from Bothrops alternatus snake venom, is described. Balt
      LAAO-I is an acidic glycoprotein, pI approximately 5.37, homodimeric, Mr
      approximately 123,000, whose N-terminal sequence is ADVRNPLE EFRETDYEVL. It
      displays a high specificity toward hydrophobic and basic amino acids, while
      deglycosylation does not alter its enzymatic activity. Balt-LAAO-I induces
      platelet aggregation and shows bactericidal activity against Escherichia coli and
      Staphylococcus aureus. In addition, this enzyme is slightly hemorrhagic and
      induces edema in the mouse paw. Balt-LAAO-I is a multifunctional enzyme with
      promising relevant biotechnological and medical applications.

PMID- 15142550
TI  - Polymer-bound reagents for the introduction of spacer-modified biotin labels.
AB  - We have developed a method for the chemoselective introduction of spacer modified
      biotin labels into unprotected multi-functional amines. A range of novel biotin
      spacer conjugates attached to a polymer-bound sulfonamide anchor was prepared
      using established amide bond forming procedures. After chemical transformation of
      the attachment site by alkylation, the resulting reactive species were utilized
      as N-selective polymer-supported biotinylation reagents. The labeled compounds,
      obtained in good to excellent yield and purity, are free of residual biotin and
      possess a custom tailored distance from the immobilization site being especially
      suited for the immobilization on streptavidin-functionalized dextran layers of
      surface plasmon resonance detector chips. In addition, derivatives displaying a
      phenyl group were synthesized in order to demonstrate the versatility of the
      procedure for the simultaneous introduction of spacer-modified biotin and a UV
      light absorbing moiety. The formation of biotin sulfoxides in the presence of in
      situ generated peroxides was investigated and is discussed. Our results suggest
      that this derivatization technique is a useful addition to the existing biotin
      labeling protocols.

PMID- 15142549
TI  - [11C]Choline as a PET biomarker for assessment of prostate cancer tumor models.
AB  - [(11)C]Choline has been evaluated as a positron emission tomography (PET)
      biomarker for assessment of established human prostate cancer tumor models.
      [(11)C]Choline was prepared by the reaction of [(11)C]methyl triflate with 2
      dimethylaminoethanol (DMAE) and isolated and purified by solid-phase extraction
      (SPE) method in 60-85% yield based on [(11)C]CO(2), 15-20 min overall synthesis
      time from end of bombardment (EOB), 95-99% radiochemical purity and specific
      activity >0.8 Ci/micromol at end of synthesis (EOS). The biodistribution of
      [(11)C]choline was determined at 30 min post iv injection in prostate cancer
      tumor models C4-2, PC-3, CWR22rv, and LNCaP tumor-bearing athymic mice. The
      results showed the accumulation of [(11)C]choline in these tumors was 1.0% dose/g
      in C4-2 mouse, 0.4% dose/g in PC-3 mice, 3.2% dose/g in CWR22rv mice, and 1.4%
      dose/g in LNCaP mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were
      2.3 (T/M, C4-2), 1.4 (T/M, PC-3), 2.5 (T/M, CWR22rv), 1.2 (T/M, LNCaP) and 2.6
      (T/B, C4-2), 2.6 (T/B, PC-3), 7.8 (T/B, CWR22rv), 3.2 (T/B, LNCaP), respectively.
      The micro-PET imaging of [(11)C]choline in prostate cancer tumor models was
      acquired from a C4-2, PC-3, CWR22rv, or LNCaP implanted mouse at 30 min post iv
      injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full
      width at half-maximum) small FOV (field-of-view) PET imaging system, IndyPET-II
      scanner, developed in our laboratory, which showed the accumulation of
      [(11)C]choline in C4-2, PC-3, CWR22rv, or LNCaP tumor implanted in a nude athymic
      mouse. The initial dynamic micro-PET imaging data indicated the average T/M
      ratios were approximately 3.0 (C4-2), 2.1 (PC-3), 3.5 (CWR22rv), and 3.3 (LNCaP),
      respectively, which showed the tumor accumulation of [(11)C]choline in all four
      tumor models is high. These results suggest that there are significant
      differences in [(11)C]choline accumulation between these different tumor types,
      and these differences might offer some useful measure of tumor biological
      process.

PMID- 15142551
TI  - Functionalised 2,3-dimethyl-3-aminotetrahydrofuran-4-one and N-(3-oxo
      hexahydrocyclopenta[b]furan-3a-yl)acylamide based scaffolds: synthesis and
      cysteinyl proteinase inhibition.
AB  - A stereoselective synthesis of functionalised (2R,3R)-2,3-dimethyl-3
      amidotetrahydrofuran-4-one, its (2S,3R)-epimer and (3aR,6aR)-N-(3-oxo
      hexahydrocyclopenta[b]furan-3a-yl)acylamide cysteinyl proteinase inhibitors has
      been developed using Fmoc-protected scaffolds 6-8 in a solid-phase combinatorial
      strategy. Within these scaffolds, the introduction of an alkyl substituent alpha
      to the ketone affords chiral stability to an otherwise configurationally labile
      molecule. Preparation of scaffolds 6-8 required stereoselective syntheses of
      suitably protected alpha-diazomethylketone intermediates 9-11, derived from
      appropriately protected alpha-methylthreonines (2R,3R)-12, (2R,3S)-13 and a
      protected analogue of (1R,2R)-1-amino-2-hydroxycyclopentanecarboxylic acid 14.
      Application of standard methods for the preparation of amino acid alpha
      diazomethylketones, through treatment of the mixed anhydride or pre-formed acyl
      fluorides of intermediates 12-14 with diazomethane, proved troublesome giving
      complex mixtures. However, the desired alpha-diazomethylketones were isolated and
      following a lithium chloride/acetic acid promoted insertion reaction provided
      scaffolds 6-8. Elaboration of 6-8 on the solid phase gave alpha,beta-dimethyl
      monocyclic ketone based inhibitors 38a-f, 39a,b,d,e,f and bicyclic inhibitors 40a
      e that exhibited low micromolar activity against a variety of cysteinyl
      proteinases.

PMID- 15142552
TI  - 17beta-Estradiol nitration by peroxidase/H2O2/NO2-: a chemical assessment.
AB  - Nitration of 17beta-estradiol by H(2)O(2) and nitrite in the presence of various
      peroxidases, viz. horseradish peroxidase, lactoperoxidase, and peroxidase
      containing homogenates from bovine uteri, was systematically investigated to
      assess on a chemical basis its potential relevance to the mechanisms of
      impairment of estrogen functions under oxidative/nitrosative stress conditions.
      In the presence of excess nitrite 17beta-estradiol reacted smoothly to give 2
      nitroestradiol (1), 4-nitroestradiol (2), and 2,4-dinitroestradiol (3). With 10
      300 microM estradiol, formation yields of 1-3 were 12-55%, but dropped to 1% or
      less at lower estrogen concentration, for example, 1 microM, or in plasma as the
      reaction medium. Time course analysis showed that 2 is the prevalent nitration
      product under conditions of slow generation of nitrating species, suggesting some
      regioselectivity for estradiol nitration at C-4, whereas 1 prevails with bolus
      addition of reagents, due to faster degradation of 2. Competition experiments
      carried out with (15)NO(2)- showed that 2 is about twice more susceptible to
      nitration than 1 as determined by (15)N NMR analysis of the resulting 3. The
      biological effects of 1 and 2 were preliminarily tested on in vitro bovine embryo
      cultures. When 1 and 2 were substituted to the standard 17beta-estradiol in the
      oocyte maturation, a significant decrease in both cleavage and blastocyst
      efficiency was observed in the case of 1 but not 2. Overall, these results
      suggest that estradiol nitration is a potential pathway of hormonal dysfunction
      and toxicity but would require elevated estrogen levels of questionable
      physiological relevance.

PMID- 15142553
TI  - Modeling and interactions of Aspergillus fumigatus lanosterol 14-alpha
      demethylase 'A' with azole antifungals.
AB  - Recent identification of the sterol 14-alpha demethylase genes (CYP51 A and B)
      from Aspergillus fumigatus and other species by Mellado et al. (J. Clin.
      Microbiol. 2001, 39(7), 2431-2438), has opened up possibilities of investigating
      the interactions of azole antifungals with the enzyme(s) from fungi. This study
      describes for the first time, a model of the three-dimensional structure of A.
      fumigatus 14-alpha demethylase (AF-CYP51A), using the crystal structure of
      Mycobacterium tuberculosis 14-alpha demethylase (PDB code:1EA1) as a template.
      The paper also describes the various interactions between azole antifungals and
      the target from A. fumigatus (AF-CYP51A). Quantitative evaluation of these
      interactions is done using COMBINE analysis to understand contributions of active
      site residues to ligand activity. It also provides explanation for the
      activity/inactivity of different ligands for AF-CYP51A.

PMID- 15142554
TI  - Lipophilic conjugates of methotrexate with short-chain alkylamino acids as DHFR
      inhibitors. Synthesis, biological evaluation, and molecular modeling.
AB  - Pursuing previous researches on lipophilic conjugates of methotrexate, aimed at
      over-crossing a form of transport resistance shown by some tumor cell lines
      toward the drug, a new series of derivatives is described in which the drug alpha
      and gamma-carboxyl groups have been linked through amide bonds to short-chain
      alpha-alkylamino acids (4-6 carbon atoms). A specific NMR study was performed to
      delineate the stereochemistry of the conjugates. The inhibitory activity of these
      compounds against the target enzyme, (bovine liver) dihydrofolate reductase, and
      a sensitive (CCRF-CEM) and a transport-resistant tumor cell subline (CEM-MTX)
      were assessed. The conjugates showed the ability of retaining the same inhibitory
      activity also against the resistant cell subline, against which the parent drug
      was much less active than against the wild one; the alpha,gamma-bis(hexyl)
      derivative was the most active term of the series. Docking studies are in
      agreement with the proposed mode of interaction of these conjugates with the
      human DHFR.

PMID- 15142555
TI  - Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase.
AB  - 2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner
      Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG
      from pyruvate and D-glyceraldehyde 3-phosphate through a class I Schiff base
      mechanism. On the basis of aldolase mechanistic pathway, various pyruvate
      analogues bearing beta-diketo structures were designed and synthesized as
      potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by
      forming stabilized iminium ion or conjugated enamine were investigated by
      enzymatic kinetics and UV-vis difference spectroscopy. Depending of the
      substituent R (methyl or aromatic ring), a competitive or a slow-binding
      inhibition takes place. These results were examined on the basis of the three
      dimensional structure of the enzyme.

PMID- 15142556
TI  - Saccharides as efficacious solubilisers for highly lipophilic compounds in
      aqueous media.
AB  - The bioavailability of lipophilic substrates is critical for biotransformations
      with isolated enzymes as well as with whole cells. With the example of a series
      of lipophilic ketones the suitability of saccharides as potent solubilisers for
      highly lipophilic substrates was demonstrated. Best results were obtained for d
      glucose, which increased substrate solubility up to 50 times. In whole-cell
      biocatalysis the sugar acts both as solubiliser and as carbon source for which
      reason this procedure does not impair cell physiology and is unique in being
      environmentally benign. The capability of saccharides to solubilise lipophilic
      compounds in aqueous media sources from their ability to form hydrophilic and
      lipophilic domains at hydrophobic interfaces, thus forming cyclodextrin-like
      structures around the lipophilic substrate.

PMID- 15142557
TI  - A TOPS-MODE approach to predict affinity for A1 adenosine receptors. 2
      (Arylamino)adenosine analogues.
AB  - The TOPological Sub-Structural Molecular Design (TOPS-MODE) approach has been
      applied to the study of the affinity of A(1) adenosine receptor of different 2
      (arylamino)adenosine analogues. A model able to describe closed to 79% of the
      variance in the values for binding experiments of 32 analogues of these compounds
      through multilinear regression analysis (MRA) was developed with the use of the
      mentioned approach. In contrast, no one of seven different approaches, including
      the use of Constitutional, Topological, Molecular walk counts, BCUT, Randic
      Molecular profiles, Geometrical, and RDF descriptors was able to explain more
      than 70% of the variance in the mentioned property with the same number of
      descriptors. In addition, the TOPS-MODE approach permitted to find the
      contribution of different fragments to the biological property giving to the
      model a straightforward structural interpretability.

PMID- 15142560
TI  - Tyrenes: synthesis of new antiproliferative compounds with an extended
      conjugation.
AB  - A series of substituted styryl-acrylonitriles was designed and synthesized. The
      new compounds, called tyrenes, were tested for the ability to inhibit acute
      lymphocytic leukemia (ALL) cancer cell growth, as well as on their toxicity to
      normal bone marrow (NBM) cells. The results showed that 3,4-dihydroxystyryl
      acrylonitriles, in particular CR-4, revealed great potency as antitumor agents,
      and also exhibited low toxicity to normal cells. The effectiveness of these
      compounds with extended conjugation may be due to their possible functioning as
      reactive Michael acceptors.

PMID- 15142558
TI  - Modulation of adenosine receptor affinity and intrinsic efficacy in adenine
      nucleosides substituted at the 2-position.
AB  - We studied the structural determinants of binding affinity and efficacy of
      adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine
      were combined with N(6)-substitutions known to enhance human A(3)AR affinity.
      Selectivity of binding of the analogues and their functional effects on cAMP
      production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs.
      Mainly sterically small substituents at the 2-position modulated both the
      affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased
      hA(3)AR affinity and efficacy in the cases of N(6)-(3-iodobenzyl) and N(6)-(trans
      2-phenyl-1-cyclopropyl), for which a full A(3)AR agonist was converted into a
      selective antagonist; the 2-cyano-N(6)-methyl analogue was a full A(3)AR agonist.
      The combination of N(6)-benzyl and various 2-substitutions (chloro,
      trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The
      environment surrounding the 2-position within the putative A(3)AR binding site
      was explored using rhodopsin-based homology modeling and ligand docking.

PMID- 15142561
TI  - QSPR of 3-aryloxazolidin-2-one antibacterials.
AB  - A QSPR treatment has been applied to a data set consisting of 60 3-aryloxazolidin
      2-one antibacterials to relate the in vitro minimum inhibitory concentration
      (MIC) (required to inhibiting growth of S. aureus) with theoretical molecular and
      fragment descriptors. The treatment using codessa pro descriptors leads to a
      seven-parameter model with r2 = 0.820 and r2cv = 0.758.

PMID- 15142559
TI  - New dibenzotropolone derivatives characterized from black tea using LC/MS/MS.
AB  - Theaflavins and thearubigins are major pigments in black tea, and it is generally
      accepted that they are produced by oxidation of flavan-3-ols (catechins) during
      tea fermentation. In the course of studies on the oxidation mechanism of tea
      polyphenols, especially the formation of thearubigins, a method combining the
      enzymatic synthesis and LC/ESI-MS/MS analysis was developed to search for new
      higher molecular weight polymers from black tea. Three new dibenzotropolones,
      theadibenzotropolone A, B, and C, together with one new tribenzotropolone,
      theatribenzotropolone A, were formed by the reaction of theaflavins and tea
      catechins with horseradish peroxidase in the presence of H(2)O(2). The structures
      of these new benzotropolone derivatives were elucidated on the basis of MS and 2D
      NMR spectroscopic analyses. The existence of these compounds in black tea was
      characterized by LC/ESI-MS/MS. Theadibenzotropolone A and B were the first
      benzotropolone-type trimers of catechins found in the black tea extract. The
      observation that galloyl ester groups of theaflavins can be oxidized to form di-
      or tri-benzotropolone skeletons strongly implied that this type of oxidation is
      an important pathway to extend the molecular size of thearubigins.

PMID- 15142562
TI  - Absolute stereostructures of polypodane- and octanordammarane-type triterpenes
      with nitric oxide production inhibitory activity from guggul-gum resins.
AB  - The methanolic extract from guggul-gum resin, the resin of Balsamodendron mukul,
      was found to inhibit nitric oxide production in lipopolysaccharide-activated
      mouse peritoneal macrophages (IC(50) = 13 microg/mL). From the methanolic
      extract, three new polypodane-type triterpenes, myrrhanol B and myrrhanones B and
      A acetate, and a new octanordammarane-type triterpene, epimansumbinol, were
      isolated together with 17 known compounds including progesterone and the related
      steroids. The absolute stereostructures of new triterpenes were elucidated on the
      basis of chemical and physicochemical evidence. The several constituents showed
      inhibitory effects on nitric oxide production and induction of inducible nitric
      oxide synthase.

PMID- 15142563
TI  - Antibacterial chalcones--bioisosteric replacement of the 4'-hydroxy group.
AB  - Hydroxy chalcones, for example, Licochalcone A, has for several years been known
      to be antibacterial. The low aqueous solubility and the medium antibacterial
      potency have limited the usefulness of the compounds. We describe the
      bioisosteric replacement of the essential 4'-hydroxy group in the hydroxy
      chalcones with bioisosters of varied degrees of acidity resulting in both more
      potent and more soluble compounds. The more acidic 4'-hydroxy analogues (e.g., 3'
      fluoro- or 3',5'-difluoro-) gave almost inactive compounds whereas exchanging the
      hydroxy group with a carboxy group resulted in a potent compound with a high
      aqueous solubility. Further optimisation and SAR-analysis resulted in soluble and
      potent carboxy chalcones [e.g., 3,5-dibromo- and 3,5-di(trifluoromethyl)-].

PMID- 15142564
TI  - Small tripeptide surrogates with low nanomolar affinity as potent inhibitors of
      the botulinum neurotoxin B metallo-proteolytic activity.
AB  - Botulinum neurotoxin type B is a high-weight (150 kDa) protein produced by the
      anaerobic bacillus Clostridium botulinum. This metallo-protease neurotoxin
      cleaves synaptobrevin, a protein, which is crucial to neurotransmission,
      resulting in the muscle paralysis, which characterizes botulism. Inhibition of
      the metallo-peptidase activity is a possible approach to obtain specific
      therapeutics to treat botulism. We have previously reported a successful attempt
      to block the proteolytic activity of this neurotoxin with new, selective amino
      thiol inhibitors endowed with Ki values in the 15-20 nanomolar range. With the
      aim of increasing the affinity and bioavailability of this first series of
      inhibitors we have optimized the residue that fits the P(1) subsite of the enzyme
      by comparing a series of ligands that contain subtle but significant variants of
      the parent structure. In addition, this strategy provided a simplification of the
      synthesis of BoNT/B inhibitors by reducing the possible number of stereoisomers.
      As such we were able to enhance the inhibitory potency whilst reducing the size
      as compared to the initial privileged structure yielding the first pseudo
      tripeptide inhibitors with Ki values in the low nanomolar range.

PMID- 15142565
TI  - Nonbonded bivalence approach to cell-permeable molecules that target DNA
      sequences.
AB  - Polyamides such as the natural antibiotic distamycin A can form binary or ternary
      complexes with B-DNA. The driving forces and advantages for forming the ternary
      complexes are not fully understood. The computational studies reported herein
      suggest that three- and four-ring polyamides have a propensity for forming the
      same dimer conformations in water as those in their ternary complexes. The pre
      dimerization of a polyamide in water facilitates the formation of the ternary
      complex, making the polyamide more selective, and tighter binding to the minor
      groove whose minimal width is predetermined by the B-DNA sequence. Relative to
      the dimer tethered with covalent bonds, the smaller, monomeric polyamide
      available from reversible dimerization in water makes the molecule inherently
      more cell permeable. A nonbonded bivalence approach that dimerizes molecules by
      intermolecular interactions is proposed for improving affinity, selectivity, and
      cell permeability.

PMID- 15142566
TI  - Efficient asymmetric syntheses, determination of absolute configurations and
      biological activities of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3
      (phenylamino)propyl]piperazine as a novel potent dopamine uptake inhibitor in the
      central nervous system.
AB  - An efficient asymmetric synthesis of the chiral N-(3-chloro-2
      hydroxypropyl)anilines (2a and 2b) was achieved through the regioselective ring
      opening reaction of chiral epichlorohydrin with aniline. This was applied to an
      asymmetric synthesis of the enantiomers of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2
      hydroxy-3-(phenylamino)propyl]piperazine 1 as a novel potent dopamine uptake
      inhibitor. Both enantiomers as trihydrochlorides, 4a.3HCl and 4b.3HCl, could be
      synthesized in good total yields and optical purities of 100% ee in three steps
      synthesis, respectively. The absolute configurations of 4a.3HCl and 4b.3HCl were
      determined using the modified Mosher's method with the related compounds, the
      intermediates (2a and 2b) and the free bases (4a and 4b). The analytical results
      indicated that 4a.3HCl and 4b.3HCl have the (S)- and (R)-configuration,
      respectively, and a series of reactions to provide them proceeded without the
      apparent influence on the stereochemistry at the chiral centers. In in vitro
      pharmacological evaluations, 4a.3HCl and 4b.3HCl showed potent dopamine
      transporter binding affinities, high dopamine, moderate serotonin, and weak
      norepinephrine uptake inhibitory activities, and 4a.3HCl exhibited a more potent
      and selective dopamine uptake inhibition over the serotonin or norepinephrine
      uptake inhibition as compared with 4b.3HCl. An ex vivo evaluation revealed that
      the oral administrations of both enantiomers at a dose of 30 mg/kg in rats
      displayed apparent dopamine uptake inhibitory activities and 4a.3HCl had a
      stronger tendency to inhibit dopamine uptake compared with 4b.3HCl.

PMID- 15142567
TI  - N-Substituted amino acid N'-benzylamides: synthesis, anticonvulsant, and
      metabolic activities.
AB  - Amino acid amides (AAA) were prepared and evaluated in seizure models. The AAA
      displayed moderate-to-excellent activity in the maximal electroshock seizure
      (MES) test and were devoid of activity in the subcutaneous Metrazol-induced
      (scMet) seizure test. The AAA anticonvulsant activity was neither strongly
      influenced by the C(2) substituent nor by the degree of terminal amine
      substitution. An in vitro metabolism study suggested that the structure-activity
      relationship pattern was due, in part, to metabolic processes that occurred at
      the N-terminal amine unit.

PMID- 15142568
TI  - Intramolecular orbital alignments in serine protease/protein inhibitor complexes.
AB  - By an analysis of PDB crystal structures, the mean conformations of protein
      strands bound in serine protease active sites are shown to contain extensively
      aligned atomic orbitals. The active-serine-bearing segment of each enzyme
      (subtilisin BPN' and beta-trypsin) also contains such alignments. The
      participating orbitals are almost identical in each system. All of the alignments
      converge on the targeted linkage. They suggest that a kind of through-strand
      polarizability is being optimized by evolution, presumably due to corresponding
      benefits in proteolysis rate. Such polarizability would help to explain the high
      values of kcat seen for long oligopeptide substrates. The idea predicts long
      substrates to be relatively reactive even under non-enzymatic conditions, which
      in fact they are.

PMID- 15142569
TI  - Proceedings from the 1st International Meeting on Microsensors and Microsystems.
      Tainan, Taiwan, 13-14 January 2003.

PMID- 15142570
TI  - Amperometric detection of morphine at a Prussian blue-modified indium tin oxide
      electrode.
AB  - In this work, the electrocatalytic oxidation of morphine (MO) at an optically
      transparent indium tin oxide (ITO) electrode modified by an electrodeposited
      Prussian blue (PB) thin film is first demonstrated, and the amperometric
      detection of MO was then investigated. Experimental results showed that the thin
      film on the ITO surface, confined to the PB/Berlin green (BG) redox pair, can
      serve as an excellent mediator which facilitates electron transfer and
      considerably lowers the overpotential required, as compared to a bare ITO
      electrode. Thus, PB can be regarded as a promising artificial peroxidase for MO.
      The rate of such an electrocatalytic reaction is pH dependent with the highest
      value at pH 5. By potential-step excitation from 0.55 to 0.70 V, a linear
      calibration curve, displaying the relationship between steady-state currents and
      MO concentrations (ranging from 0.09 to 1.0 mM), was obtained. The detection
      sensitivity is about 16.8 microA/cm2 mM. Most importantly, the method described
      herein can readily discriminate MO analogs lacking the phenolic -OH group, such
      as codeine, and can thus benefit the specific recognition of MO.

PMID- 15142571
TI  - Amperometric acetylcholine sensor catalyzed by nickel anode electrode.
AB  - An amperometric method was using a nickel catalytic electrode in aqueous base
      solution for detecting acetylcholine (ACh). A sensing mechanism was developed in
      which ACh was hydrolyzed in base aqueous solution to produce the acetic anion and
      choline. The alcohol group of choline was oxidized to the corresponding
      carboxylic acid by Ni(OH)2/NiOOH catalytic system. The amperometric response
      resulted from the current generated by ACh oxidation in response to step changes
      in ACh concentration. The potential window of limiting current of ACh anodic
      oxidation at the Ni interface was determined in NaOH electrolyte. The effect of
      NaOH electrolyte concentration on sensitivity was also discussed. At the optimum
      operating condition, the method exhibits a good linear relationship between the
      response current and the ACh concentration. The response time of the ACh sensing
      system was 10 s. Scanning electrochemical microscopy (SECM) with platinum micro
      tips was used to investigate the diffusion layer thickness of Ni electrode.

PMID- 15142572
TI  - Urea biosensor based on PANi(urease)-Nafion/Au composite electrode.
AB  - The polyaniline (PANi)-Nafion composite film was prepared onto the ceramic plate
      by the cyclic voltammetry (CV) method with the various cycle numbers. When the
      PANi-Nafion/Au/ceramic plate with the preparing cycle number of 5 was as working
      electrode, the cathodic peak current was achieved as 84.0 microA in 60 mg dl(-1)
      NH4Cl buffer solution. On the other hand, the small cathodic peak currents for
      buffer solution in the presence of 60 mg dl(-1) LiOH, NaCl and KCl, respectively,
      were found with the same composite electrode as working electrode. The cathodic
      peak current decreased from 84.0 to 16.3 microA in the 60 mg dl(-1) NH4Cl buffer
      solution when the cycle number for preparing PANi-Nafion/Au/ceramic plate
      composite electrode with the CV method increased from 5 to 15. The enzyme of
      urease was immobilized onto the PANi-Nafion/Au/ceramic plate composite film by
      the electrochemical immobilization and the casting methods and used as sensing
      electrode to detect the concentration of urea in the buffer solution. The
      sensitivity of composite electrode immobilized with the casting method was
      greater than that of electrochemical immobilization method. The sensitivity and
      the detecting limit of the urea sensor were found to be 0.7 and 5.27 microA (mg
      dl(-1))(-1)cm(-2), as well as 6 and 0.3 mg dl(-1), respectively, when urease was
      immobilized by glutaraldehyde (GA) cross-linker and Nafion network, respectively.

PMID- 15142573
TI  - Thin film trichloroethylene electrochemical sensor.
AB  - Pt-Ti and Pb-Pt-Ti thin films were deposited on alumina substrates by sputtering
      in Ar gas. In this study, an electrodeposited Pb-modified Pt-Ti thin film working
      electrode was prepared. Optimal sensing conditions were found to be -2.10 V
      (versus Ag/Ag+ with 0.1 M tetrabutylammonium perchlorate (TBAP) in acetonitrile
      (AN) solution) sensing potential, 250 rpm agitation rate. At room temperature,
      the response time was 15 s (90% response time). The correlation of sensing
      response current, id, and trichloroethylene (TCE) concentration, CL, is id =
      2.86CL in the range from 100 to 700 ppm TCE. Additionally, the rate constant of
      (TCE) cathodic reduction was found to be 2.434 x 10(-3) cm(-1) s(-1).

PMID- 15142574
TI  - Ionic liquid ethanol sensor.
AB  - Ionic liquids containing lithium methylsulfonyl group were prepared from the
      precursors poly(propylene glycol)-block-(ethylene glycol)-block-(propylene
      glycol)-bis(2-aminopropyl ether) with different molecular weight. These liquids
      revealed excellent electrical conductivity in the temperature range -25 to 85
      degrees C. Also, they exhibited a high boiling temperature and hence a low vapor
      pressure in ambient condition. Additionally, they showed a high fluidity with
      their viscosities being comparative with that of water. To determine the
      sensitivity of an ethanol sensor by using these ionic liquids, these liquids were
      subjected into a sequential electrochemical tests with nickel electrodes which
      performed a high sensitivity for the ethanol sensor. It was found that only the
      derivative with low molecular weight could detect ethanol. Furthermore, a linear
      relationship between the response current and the concentration of ethanol was
      constructed. The detection limit was found to be 0.13% (v/v) and its response
      time was 336 s.

PMID- 15142575
TI  - A sputtered thin film of nanostructured Ni/Pt/Ti on Al2O3 substrate for ethanol
      sensing.
AB  - A novel thin film ethanol sensor using sputtered Ni/Pt/Ti on an Al2O3 substrate
      as the working electrode in an alkaline solution was developed. Atomic force
      microscopy (AFM) and scanning electron microscopy (SEM) were used to characterize
      the nanostructure of nickel films. Sputtering deposition conditions for maximum
      catalytic efficiency, electrode selectivity, and reproducibility were discussed.
      The results showed that ethanol oxidation was more efficient on the sputtered
      Ni/Pt/Ti on an Al2O3 substrate electrode than that on the conventional nickel
      electrode. The optimal operating conditions to generate the sputtered Ni/Pt/Ti on
      the Al2O3 substrate electrode were: 45 min of Ni sputtering deposition time, and
      50 W of Ni sputtering power. The results also indicated that the response time of
      the prepared ethanol sensor is 27 s and the best sensitivity is 3.08 microA
      microM(-1) cm(-2).

PMID- 15142576
TI  - A low-voltage wide-input CMOS comparator for sensor application using back-gate
      technique.
AB  - In this paper, two new analog CMOS comparators (Type-I and Type-II) with low
      voltage and wide-input capabilities are proposed. The comparator receives two
      analog inputs and puts out one digital state to identify the larger (or the
      smaller) of the input variables, which represents an useful operation in data
      conversion and sensory signal processing. Without using special fabrication
      technologies, the supply voltage of the circuit is reduced to 1 V. Due to the
      utilization of CMOS back-gate technique, the input range of the comparators is
      greatly improved. The comparators are composed of bulk-driven stage and dynamic
      latch. By using a CMOS n-well technology, the results of HSPICE simulations
      indicate that the response time of Type-I circuit is 1 micros under 10 mV
      identified resolution. Type-II comparator achieves 5 mV identified resolution.
      The input dynamic ranges of the comparators are approximately rail-to-rail.

PMID- 15142578
TI  - An FET-type charge sensor for highly sensitive detection of DNA sequence.
AB  - We have fabricated an field effect transistor (FET)-type DNA charge sensor based
      on 0.5 microm standard complementary metal oxide semiconductor (CMOS) technology
      which can detect the deoxyribonucleic acid (DNA) probe's immobilization and
      information on hybridization by sensing the variation of drain current due to DNA
      charge and investigated its electrical characteristics. FET-type charge sensor
      for detecting DNA sequence is a semiconductor sensor measuring the change of
      electric charge caused by DNA probe's immobilization on the gate metal, based on
      the field effect mechanism of MOSFET. It was fabricated in p-channel (P) MOSFET
      type because the phosphate groups present in DNA have a negative charge and this
      charge determines the effective gate potential of PMOSFET. Gold (Au) which has a
      chemical affinity with thiol was used as the gate metal in order to immobilize
      DNA. The gate potential is determined by the electric charge which DNA possesses.
      Variation of the drain current versus time was measured. The drain current
      increased when thiol DNA and target DNA were injected into the solution, because
      of the field effect due to the electrical charge of DNA molecules. The
      experimental validity was verified by the results of mass changes detected using
      quartz crystal microbalance (QCM) under the same measurement condition. Therefore
      it is confirmed that DNA sequence can be detected by measuring the variation of
      the drain current due to the variation of DNA charge and the proposed FET-type
      DNA charge sensor might be useful in the development for DNA chips.

PMID- 15142577
TI  - Preparation and characterization of thick-film Ni/MH battery.
AB  - Using the porous polypropylene (PP) films sputtered with gold and the Ni as
      current collectors, the electroactive materials (Ni(OH)2 and metal hydride (MH))
      of positive and negative electrodes were prepared on the current collector using
      thick-film technology. Two types of cell configurations were prepared and the
      characteristics of these batteries were compared. The cycle number for the
      formation of batteries based on the porous PP film was found to be 2, which was
      significantly less than that of batteries based on the ceramic substrates. Using
      the porous PP film as substrate, the number of cycles for the formation of
      battery increased from 2 to 5 with the increase of the charge/discharge rate from
      0.1C/0.025C to 2.0C/0.5C. The silver oxides dendrites formed by the oxidation of
      silver paste used to adhere the current collectors and the conducting wires in
      the charge/discharge process caused a short contact between the positive and
      negative electrodes, which then caused the battery failure. The cycle life of the
      battery based on the porous PP film was found to be greater than 400 when the
      charge/discharge rate was 2.0C/0.5C.

PMID- 15142579
TI  - Determination of albumin concentration by MIP-QCM sensor.
AB  - An MIP-QCM sensor able to detect micro-determine albumin concentrations was
      prepared by imprinting albumin with 3-dimethylaminopropyl methacrylamide
      acrylate. The albumin MIP was coated on a QCM Au electrode. The adsorption
      characteristics of different electrodes, such as Au-OH, Au-COOH, Au-NH2 and Au
      electrodes, with albumin or mixture was examined. In the tetraethyleneglycol
      dimethacrylate crosslinking agent system, the adsorption capacity of different Au
      electrodes is in the order Au-OH > Au-COOH > Au-NH2 > Au. Additionally, the time
      taken to receive a steady-state frequency is in the order Au-NH2 < Au-OH < Au
      COOH < Au. However, in the trimethylolpropane trimethacrylate crosslinking agent
      system, the adsorption capacity is in the order Au > Au-NH2 > Au-OH > Au-COOH
      electrode. Hence, the crosslinking agent had a significant effect on the MIP-QCM.
      On the adsorption selectivity, the albumin MIP-QCM exhibited higher response to
      albumin, the adsorption mass ratio of cytochrome c:lysozyme:albumin:myoglobin was
      160:1:1942:30. On the other hand, in the non-MIP-QCM, the adsorption mass ratio
      of cytochrome c:lysozyme:albumin:myoglobin was 13:1:249:86. Additionally, a
      linear fitting was established and a clinical real sample was tested. This novel
      potential application of molecular imprinting to the recognition element of an
      MIP-QCM sensor appears to be promising.

PMID- 15142580
TI  - Integrated optical-fiber capillary electrophoresis microchips with novel spin-on
      glass surface modification.
AB  - This paper presents a novel micro-capillary electrophoresis (CE) chip with
      embedded optical fibers for the on-line detection of DNA samples. The optical
      fibers are pre-etched and then inserted directly into fiber channels incorporated
      within low-cost soda-lime glass substrates. The embedded optical fibers are
      precisely aligned with the microfluidic channels such that the induced
      fluorescence signals from labeled bio-samples can be detected. This arrangement
      avoids the requirement for delicate optical alignment procedures and equipment.
      Surface modification of the CE channels is accomplished by means of a simple and
      reliable organic-based spin-on-glass (SOG) method. The zeta potential
      distribution and the corresponding electroosmotic mobility of the fluid are
      simulated numerically for the modified and non-modified channel surfaces, and
      then both sets of results are verified experimentally. The present results
      indicate that the value of the zeta potential for a surface with an SOG coating
      is 19.3 times smaller than that of an untreated surface. A phiX-174 DNA marker
      fluid is used to evaluate the injection and separation performance of the
      developed micro-CE device. Furthermore, the long-term stability of the SOG-coated
      surface is also investigated. The experimental data reveal that the microchip
      device is capable of providing highly efficient separations of bio-molecules, and
      that the SOG layer retains its low zeta potential characteristics for at least 45
      days. The present results confirm the effectiveness of the proposed micro-CE chip
      in performing the on-line detection of DNA samples, and indicate that the SOG
      process represents a simple and reliable solution for the surface modification of
      glass-based microchannels.

PMID- 15142581
TI  - Design and fabrication development of a micro flow heated channel with
      measurements of the inside micro-scale flow and heat transfer process.
AB  - The current work provides a design and fabrication technique for a micro channel
      system that can provide a uniform heat flux boundary condition on the channel
      wall and a well insulation on the wall to prevent heat loss from the channel to
      the outside ambient. Therefore, detailed micro-scale flow and heat transfer
      process and information along the channel can be studied. Semiconductor sensor
      material was selected to fabricate both the heaters and the arrays of temperature
      sensors on a silicon substrate. These heaters and sensors were then moved to a
      low thermal conductivity epoxy-glass substrate for fabrication of the channel.
      Design consideration and fabrication techniques involved in this processes will
      be discussed. A final measurement for the validation of the heaters and the
      sensors fabricated and a study of the flow friction behavior and the heat
      transfer coefficient distributions inside the micro channel will be presented.
      The local Nusselt number distrubution inside the micro channel is reported the
      first time in the open literature.

PMID- 15142582
TI  - Thermal chip fabrication with arrays of sensors and heaters for micro-scale
      impingement cooling heat transfer analysis and measurements.
AB  - The design and fabrication for a thermal chip with an array of temperature
      sensors and heaters for study of micro-jet impingement cooling heat transfer
      process are presented. This thermal chip can minimize the heat loss from the
      system to the ambient and provide a uniform heat flux along the wall, thus local
      heat transfer processes along the wall can be measured and obtained. The
      fabrication procedure presented can reach a chip yield of 100%, and every one of
      the sensors and heaters on the chip is in good condition. In addition, micro-jet
      impingement cooling experiments are performed to obtain the micro-scale local
      heat transfer Nusselt number along the wall. Flow visualization for the micro
      impinging jet is also made. The experimental results indicate that both the micro
      scale impinging jet flow structure and the heat transfer process along the wall
      is significantly different from the case of large-scale jet impingement cooling
      process.

PMID- 15142583
TI  - Simulation of two-dimensional fully developed laminar flow for a magneto
      hydrodynamic (MHD) pump.
AB  - MHD micro-pumps circumvent the wear and fatigue caused by high pressure-drop
      across the check valves of mechanical micro-pumps in micro-fluidic systems. Early
      analyses of the fluid flow for MHD micro-pumps were mostly made possible by the
      Poiseuille flow theory; however, this conventional laminar approach cannot
      illustrate the effects of various channel sizes and shapes. This paper,
      therefore, presents a simplified MHD flow model based upon steady state,
      incompressible and fully developed laminar flow theory to investigate the
      characteristics of a MHD pump. Inside the pump, flowing along the channel is the
      electrically conducting fluid flowing driven by the Lorentz forces in the
      direction perpendicular to both dc magnetic field and applied electric currents.
      The Lorentz forces were converted into a hydrostatic pressure gradient in the
      momentum equations of the MHD channel flow model. The numerical simulations
      conducted with the explicit finite difference method show that the channel
      dimensions and the induced Lorentz forces have significant influences on the flow
      velocity profile. Furthermore, the simulation results agree well with the
      experimental results published by other researchers.

PMID- 15142584
TI  - RCA combined nanoparticle-based optical detection technique for protein
      microarray: a novel approach.
AB  - Developing a readily available biosensor with excellent performances is the main
      focus of many research groups. Recently, major breakthroughs in miniaturization
      of molecular analysis have produced DNA and protein microarrays. The aim of our
      group is to develop a sensitive technique for analyzing signals on protein
      microarray by applying the surface plasmon resonance (SPR) method. This new
      detection technique for specific molecular binding utilizes rolling circles
      amplification (RCA) post-signal processing method [Nat. Genet. 19 (1998) 225-232]
      and optical visualization by nanogold particle-labeled molecules on a micro
      structured chip surface. By covalent bonding of the RCA primer to the detection
      antibody guarantees that the linkage between the analyte and the amplified RCA
      product is maintained during the assay. Experimental results show that RCA has
      significantly enhanced sensitivity compared to conventional methods. This
      combination of an easily detectable signal with chip technology should have the
      potential to become a successful commercial application.

PMID- 15142585
TI  - Synthesis and photoluminescence study of molecularly imprinted polymers appended
      onto CdSe/ZnS core-shells.
AB  - The Photoluminescence of quantum dots have been found to be a useful tool for the
      detection of small to medium sized analyte molecules in a host-guest environment.
      By the incorporation of quantum dots into molecularly imprinted polymers, which
      can offer shape and selectivity, the former can respond by quenching the
      photoluminescence emission upon template binding. In this work host polymers were
      synthesized and cased into thin films using functional monomers such as
      methacrylic acid (MAA), CdSe/ZnS core-shell derivatized with 4-vinyl pyridine and
      ethylene glycol dimethacrylic acid (EGDMA) as a cross-linker. The intensity of
      photoluminescence emission is detected upon analyte binding.

PMID- 15142586
TI  - The fluid property dependency on micro-fluidic characteristics in the deposition
      process for microfabrication.
AB  - The droplet impingement into a cavity at micrometer-scale is one of important
      fluidic issues for microfabrications, e.g. the inkjet deposition process in the
      PLED display manufacturing. The related micro-fluidic behaviors in the deposition
      process should be carefully treated to ensure the desired quality of
      microfabrication. The droplets generally dispensing from an inkjet head, which
      contains an array of nozzles, have a volume in several picoliters, while each
      nozzle responds very quickly and jets the droplets into cavities on substrates
      with micrometer size. The nature of droplet impingement depends on the fluid
      properties, the initial state of droplet, the impact parameters and the surface
      characteristics. The commonly chosen non-dimensional numbers to describe this
      process are the Weber number, the Reynolds number, the Ohnesorge number, and the
      Bond number. This paper discusses the influences of fluid properties of a
      Newtonian fluid, such as surface tension and fluid viscosity, on micro-fluidic
      characteristics for a certain jetting speed in the deposition process via a
      numerical approach, which indicates the impingement process consists of four
      different phases. In the first phase, the droplet stretching outwards rapidly,
      where inertia force is dominated. In the second phase, the recoiling of droplet
      is observed, where surface tension becomes the most important force. In the third
      phase, the gravitational force pulls the droplet surface towards cavity walls.
      The fourth phase begins when the droplet surface touches cavity walls and ends
      when the droplet obtains a stable shape. If the fluid viscosity is relatively
      small, the droplet surface touches cavity walls in the second phase. A stable
      fluid layer would not form if the viscosity is relatively small.

PMID- 15142587
TI  - Frequency bandwidth limitation of external pulse electric field in microchannels.
      Applications to analyte velocity modulation detections.
AB  - Pulse field driven electro-separations have been used for different analytical
      advantages, such as signal quality improvement and separation performance
      improvement. We have studied the temporal electro-osmosis in microchannels due to
      viscous diffusivity under the external pulse electric fields. Theoretical studies
      derived from Navier-Stokes equations conclude the dependence of the time to
      steady state electro-osmosis on the channel sizes. Pulse field frequency should
      be limited by the electro-osmosis setting-in time. We also observed the unstable
      electro-osmosis as the external field frequency increases. As channel geometry
      characterization results are employed in the mathematical models, the threshold
      frequencies obtained in experimental data are consistent with the computational
      predictions. In previous studies, effective signal quality improvement of electro
      separations has been demonstrated, when external pulse fields modulate analyte
      velocities with synchronous lock-in detection. The results indicate signal-to
      noise ratio improvement would be more significant at the high frequency regime
      where flicker noise is not dominant. Since bandwidth limitation due to fluid
      viscosity constrains the pulse frequency, optimum analyte velocity modulation is
      in need of further investigation. Under the bandwidth constrains, we have
      investigated the theoretical optimum modulation frequencies.

PMID- 15142588
TI  - Study of sweet taste evaluation using taste sensor with lipid/polymer membranes.
AB  - The higher sensitivity for sweeteners can be achieved by newly developed
      lipid/polymer membranes. The membrane is composed of lipids such as phosphoric
      acid di-n-hexadecyl ester and tetradodecylammoniumbromid, and a plasticizer,
      dioctyl phenylphosphonate. As a result of changing electric charge of the
      membrane surface, the newly developed membrane shows 5-10 times higher
      sensitivity for sucrose than the conventional ones. We also applied the sensor to
      other sugars such as sugar alcohol which is used as alternative sweetness or food
      additives. The experimental results of other sweeteners relatively correspond to
      human sensory evaluation, though the sensitivity for some sugars need to be
      improved.

PMID- 15142589
TI  - A performance comparison of choline biosensors: anodic or cathodic detections of
      H2O2 generated by enzyme immobilized on a conducting polymer.
AB  - Amperometric choline biosensors were fabricated by the covalent immobilization of
      an enzyme of choline oxidase (ChO) and a bi-enzyme of ChO/horseradish peroxidase
      (ChO/HRP) onto poly-5,2':5',2"-terthiophene-3'-carboxylic acid (poly-TTCA)
      modified electrodes (CPMEs). A sensor modified with ChO utilized the oxidation
      process of enzymatically generated H(2)O(2) in a choline solution at +0.6V. The
      other one modified with ChO/HRP utilized the reduction process of H(2)O(2) in a
      choline solution at -0.2V. Experimental parameters affecting the sensitivity of
      sensors, such as pH, applied potential, and temperature were optimized. A
      performance comparison of two sensors showed that one based on ChO/HRP/CPME had a
      linear range from 1.0 x 10(-6) to 8.0 x 10(-5) M and the other based on ChO/CPME
      from 1.0 x 10(-6) to 5.0 x 10(-5) M. The detection limits for choline employing
      ChO/HRP/CPME and ChO/CPME were determined to be about 1.0 x 10(-7) and 4.0 x 10(
      7) M, respectively. The response time of sensors was less than 5s. Sensors showed
      good selectivity to interfering species. The long-term storage stability of the
      sensor based on ChO/HRP/CPME was longer than that based on ChO/CPME.

PMID- 15142590
TI  - On-chip biosensing of estrogen receptor-alpha at single molecular level.
AB  - A novel method for detecting interaction between DNA and DNA-binding protein at
      single molecular level has been proposed. In this study, estrogen receptor-alpha
      (ER-alpha) was used for biosensing as the proof-example. A 518 bp-long (ca. 176
      nm) DNA probe labeled with streptavidin at its 5'-terminus was prepared by
      inserting a consensus oligonucleotide sequence that binds to ER-alpha. A solution
      containing ER-alpha was dropped onto the Ni-treated mica substrate on which the
      DNA prove was previously immobilized, and it was observed by AFM. Specific
      binding of ER-alpha could be observed by measuring the distance between the site
      where binding occur, to the streptavidin label.

PMID- 15142591
TI  - Monitoring haemodialysis using electronic nose and chemometrics.
AB  - An ever-increasing number of patients have to undergo regular renal dialysis to
      compensate for acute or chronic renal failure. The adequacy of the treatment has
      a profound effect on patients' morbidity and mortality. Therefore, it is
      necessary to assess the delivered dialysis dose. For the quantification of the
      dialysis dose, two parameters are most commonly used, namely the K(t)/V value
      (normalised dose of dialysis) and the urea reduction rate, yet the prescribed
      dialysis dose often differs from the actual delivered dialysis dose. Currently,
      no interactive process is available to ensure optimal treatment. The aim of this
      study was to investigate the potential for an "electronic nose" as a novel
      monitoring tool for haemodialysis. Blood samples were analysed using an
      electronic nose, comprising an array of 14 conducting polymer sensors, and
      compared to traditional biochemistry. Principal component analysis and
      hierarchical cluster analysis were applied to evaluate the data, and demonstrated
      the ability to distinguish between pre-dialysis blood from post-dialysis blood
      independent of the method used. It is concluded that the electronic nose is
      capable of discriminating pre-dialysis from post-dialysis blood and hence,
      together with an appropriate classification model, suitable for on-line
      monitoring.

PMID- 15142592
TI  - Immobilization and hybridization by single sub-millisecond electric field pulses,
      for pixel-addressed DNA microarrays.
AB  - Single square voltage pulses applied to buried electrodes result in dramatic rate
      increases for (1) selective covalent bonding (immobilization) of single-stranded
      DNA (ssDNA) probes to a functionalized thin film SiO(2) surface on a plastic
      substrate and (2) hybridization of ssDNA to the immobilized probe. DNA
      immobilization and hybridization times are 100 ns and 10 micros, respectively,
      about 10(9) times faster than the corresponding passive reactions without
      electric field. Surface coverage is comparable. Duration, magnitude and slew rate
      of the voltage pulse are all key factors controlling the rates of ssDNA
      immobilization and hybridization. With rise times of 4.5 ns, pulses shorter than
      1 ms and voltages below 1V are effective. The ssDNA adsorbed on the surface is
      reoriented by the rapidly changing electric field. This reduces steric barriers
      and speeds the immobilization and hybridization reactions. These results open the
      way for pixel-addressed microarrays driven by silicon microelectronics circuits.

PMID- 15142593
TI  - Neurons as sensors: individual and cascaded chemical sensing.
AB  - A single neuron sensor has been developed based on the interaction of gradient
      electric fields and the cell membrane. Single neurons are rapidly positioned over
      individual microelectrodes using positive dielectrophoretic traps. This enables
      the continuous extracellular electrophysiological measurements from individual
      neurons. The sensor developed using this technique provides the first
      experimental method for determining single cell sensitivity; the speed of
      response and the associated physiological changes to a broad spectrum of chemical
      agents. Binding of specific chemical agents to a specific combination of
      receptors induces changes to the extracellular membrane potential of a single
      neuron, which can be translated into unique "signature patterns" (SP), which
      function as identification tags. Signature patterns are derived using Fast
      Fourier Transformation (FFT) analysis and Wavelet Transformation (WT) analysis of
      the modified extracellular action potential. The validity and the sensitivity of
      the system are demonstrated for a variety of chemical agents ranging from
      behavior altering chemicals (ethanol), environmentally hazardous agents (hydrogen
      peroxide, EDTA) to physiologically harmful agents (pyrethroids) at pico- and
      femto-molar concentrations. The ability of a single neuron to selectively
      identify specific chemical agents when injected in a serial manner is
      demonstrated in "cascaded sensing".

PMID- 15142594
TI  - Enzyme-mediated amperometric biosensors prepared with the Layer-by-Layer (LbL)
      adsorption technique.
AB  - Glucose oxidase (GOD) has been immobilized in Layer-by-Layer (LbL) films,
      adsorbed alternately with poly(allylamine) hydrochloride (PAH) layers, onto an
      ITO substrate modified with a Prussian Blue (PB) layer. The ITO/PB/GOD-PAH
      heterostructures were tested in amperometric glucose biosensors, with a high
      sensitivity of 16 microA mmol(-1)lcm(-2) and a limit of detection of 0.20 mmoll(
      1) being achieved. This high sensitivity is attributed to the ultrathin nature of
      the film in addition to the low operating potentials that could be used due to
      the efficient catalysis of H(2)O(2) produced in the enzymatic reaction in the
      presence of Prussian Blue. The biosensors are highly selective to glucose, as
      demonstrated by the lack of interference from possible interferents such as
      ascorbic and uric acids and acetominophen. The stability of the biosensors was
      checked by observing an almost constant sensitivity for a period of approximately
      20 days, thus indicating a stable adsorption of GOD.

PMID- 15142595
TI  - Amperometric enzyme electrodes for aerobic and anaerobic glucose monitoring
      prepared by glucose oxidase immobilized in mixed ferrocene-cobaltocenium
      dendrimers.
AB  - The enzyme glucose oxidase (GOx) has been immobilized electrostatically onto
      carbon and platinum electrodes modified with mixed ferrocene-cobaltocenium
      dendrimers. The ferrocene units have been used successfully as mediators between
      the GOx and the electrode under anaerobic conditions. In experiments carried out
      in the presence of oxygen, the cobaltocenium moieties act as electrocatalysts in
      the reduction of the oxygen in the solution, thus making possible the
      determination of the oxygen variation due to the enzymatic reaction, with high
      sensitivity. The current response of the electrode was determined by measuring
      steady-state current values obtained applying a constant potential. The effect of
      the substrate concentration, the dendrimer generation, the thickness of the
      dendrimer layer, interferences, and storage on the response of the sensors were
      investigated.

PMID- 15142596
TI  - Detection of serum uric acid using the optical polymeric enzyme biochip system.
AB  - An optical polymeric biochip system based on the complementary metal oxide
      semiconductor (CMOS) photo array sensor and polymeric enzyme biochip for rapidly
      quantitating uric acid in a one-step procedure was developed. The CMOS sensor was
      designed with N(+)/P-well structure and manufactured using a standard 0.5 microm
      CMOS process. The polymeric enzyme biochip was immobilized with uricase
      peroxidase and used to fill the reacting medium with the sample. This study
      encompasses the cloning of the Bacillus subtilis uricase gene and expression in
      Escherichia coli, as well as the purification of uricase and measurement of its
      activity. The cloned uricase gene included an open reading frame of 1491
      nucleotides that encodes a protein of approximately 55 kDa. The expression of the
      putative MBP-fusion protein involved approximately 98 kDa of the protein. The
      CMOS sensor response was stronger at a higher temperature range of 20-40 degrees
      C, with optimal pH at 8.5. The calibration curve of purified uric acid was linear
      in the concentration range from 2.5 to 12.5 mg/dL. The results obtained for serum
      uric acid correlated quite closely with those obtained using the Beckman Synchron
      method.

PMID- 15142597
TI  - Polyaniline-uricase biosensor prepared with template process.
AB  - Polyaniline (PANI) uricase biosensor prepared with template process is reported
      first in this paper. The fabrication process is as follows. Firstly, a PANI
      uricase electrode is obtained using one-step process. Secondly, the electrode is
      hydrolyzed in 6.0 mol/dm(3) hydrochloric acid solution to remove the uricase that
      may be affected by aniline monomer from PANI film. Finally, active uricase is
      immobilized into the PANI film based on the principle of the doping and undoping
      of the conducting polymer and a PANI-uricase biosensor is obtained. Some factors
      that affect response current are studied, such as temperature, pH, potential and
      substrate concentration. The determination of biosensors indicates that the
      response current of the biosensor prepared by template process decreases only by
      about 18% for 60 days, but that prepared by two-step process decreases by
      approximately 39% for 40 h. The uricase in PANI-uricase biosensor prepared by
      template process mainly interacts with the nitrogen linked to the quinoid ring.
      The biosensor is characterized with FTIR, UV-Vis and SEM for the first time.

PMID- 15142598
TI  - Urea potentiometric biosensor based on modified electrodes with urease
      immobilized on polyethylenimine films.
AB  - The development of a new electrochemical sensor consisting in a glass-sealed
      metal microelectrode coated by a polyethylenimine film is described. The use of
      polymers as the entrapping matrix for enzymes fulfils all the requirements
      expected for these materials without damaging the biological material. Since
      enzyme immobilization plays a fundamental role in the performance characteristics
      of enzymatic biosensors, we have tested four different protocols for enzyme
      immobilization to determine the most reliable one. Thus the characteristics of
      the potentiometric biosensors assembled were studied and compared and it appeared
      that the immobilization method leading to the most efficient biosensors was the
      one consisting in a physical adsorption followed by reticulation with dilute
      aqueous glutaraldehyde solutions. Indeed, the glutaraldehyde immobilized urease
      sensor provides many advantages, compared to the other types of sensors, since
      this type of urea biosensor exhibits short response times (15-30s), sigmoidal
      responses for the urea concentration working range from 1 x 10(-2.5) to 1 x 10(
      1.5) M and a lifetime of 4 weeks.

PMID- 15142599
TI  - Orientated binding of photosynthetic reaction centers on gold using Ni-NTA self
      assembled monolayers.
AB  - Coupling of photosynthetic reaction centers (RCs) with inorganic surfaces is
      attractive for the identification of the mechanisms of interprotein electron
      transfer (ET) and for possible applications in construction of photo- and
      chemosensors. Here we show that RCs from Rhodobacter sphaeroides can be
      immobilized on gold surfaces with the RC primary donor looking towards the
      substrate by using a genetically engineered poly-histidine tag (His(7)) at the C
      terminal end of the M-subunit and a Ni-NTA terminated self-assembled monolayer
      (SAM). In the presence of an electron acceptor, ubiquinone-10, illumination of
      this RC electrode generates a cathodic photocurrent. The action spectrum of the
      photocurrent coincides with the absorption spectrum of RC and the photocurrent
      decreases in response to the herbicide, atrazine, confirming that the RC is the
      primary source of the photoresponse. Disruption of the Ni-NTA-RC bond by
      imidazole leads to about 80% reduction of the photocurrent indicating that most
      of the photoactive protein is specifically bound to the electrode through the
      linker.

PMID- 15142600
TI  - Blood rheological characterization using the thickness-shear mode resonator.
AB  - Thickness-shear mode (TSM) resonators have been used to characterize static
      rheological properties of plasma and whole blood samples. We demonstrated simple
      and rapid techniques for determining plasma viscosity without cell separation,
      for measuring erythrocyte sedimentation rate, and for tracking blood coagulation
      throughout the entire process. Additionally, mathematical models, previously
      developed to characterize surface-loaded resonators, were used to extract non
      Newtonian and viscoelastic material properties of blood layers during
      sedimentation and coagulation experiments. These studies indicate the utility of
      the TSM resonator for several clinical applications. Because the resonators can
      be miniaturized, potential exists for extending the techniques for use inside the
      body or blood stream (in vivo).

PMID- 15142601
TI  - Organic plasma process for simple and substrate-independent surface modification
      of polymeric BioMEMS devices.
AB  - A polymeric bio micro electromechanical systems (BioMEMS) device was fabricated
      using organic plasma polymerization, by which the surface of a polymeric
      substrate could easily be modified through vapor-phase deposition of organic thin
      films. This technique, capable of polymeric deposition of any kind of monomer,
      can serve the purpose of anti-fouling coating, wettability control, or layer-to
      layer interface creation, on the surface of any given chemically-inert polymeric
      substrate without involving cumbersome surface organic reactions. A prototype
      device was fabricated to have an array of electrochemical glucose biosensors with
      the three electrode configuration, each of which has a microfluidic channel (500
      microm x 800 microm) for capillary-action-driven sample delivery and the
      concerned enzymatic reaction. Stressing the advantages of the plasma
      polymerization process using a polymeric substrate together with some additional
      features accomplished in our device fabrication, new possibilities in the field
      of polymeric BioMEMS are discussed.

PMID- 15142602
TI  - Combinatorial augmentation for a multi-pathogen biosensor: signal analysis and
      design.
AB  - Recent advances in combinatorial chemistries have revolutionized approaches to
      drug candidate synthesis and screening. Combinatorial approaches are also
      beginning to be used to increase the performance of diagnostic devices for both
      clinical and field uses. The use of combinatorial technologies is motivated by a
      general desire to detect as many different pathogens using the smallest, most
      inexpensive and fastest system possible. We examine the potential for rational
      design approaches to enhance the performance and miniaturization of biosensors.
      We describe novel combinatorial biosensor systems, in addition to mathematical
      frameworks for their optimization and performance prediction. The biosensors are
      assumed to be composed of multiple detection channels with the following
      characteristics. Each channel has a single output and can be dynamically set to
      respond to some or all of a set of pathogens. Regardless of the number of
      pathogens detected, however, there is a single numerical output from a channel.
      We evaluate the amount of ambiguity of positive signals produced as a result of
      increasing both the number of channels and the number of pathogens detected per
      channel and the effect this ambiguity has on system performance. We further
      discuss strategies for disambiguating positive signals. Finally we cite specific
      biosensor configurations that exploit the findings above and compare them to
      "brute force" approaches. Overall we suggest the approach we refer to as "n
      squared" to simultaneously optimize device cost, speed and reagent usage.

PMID- 15142603
TI  - Catheter-based impedance measurements in the right atrium for continuously
      monitoring hematocrit and estimating blood viscosity changes; an in vivo
      feasibility study in swine.
AB  - Hematocrit is the most important determinant of whole blood viscosity and it
      affects thrombosis. As hematocrit can be measured accurately in vitro by using an
      electrical impedance technique, aim of the present study is to investigate the
      diagnostic potential of using this technique in vivo to continuously monitor
      hematocrit. Characteristics of a special catheter for in vivo measurement of
      electrical resistivity in blood in the right atrium are described. In five
      anesthetized swine hematocrit is monitored continuously with this catheter while
      different levels of hemoconcentration are induced. In addition, blood viscosity
      is increased by inducing 'acute phase' reaction the day before surgery, resulting
      in variable degree of elevated fibrinogen levels in the five swine. Good
      reproducibility of the resistivity measurements (S.D < 0.01) and excellent
      correlation between resistivity data in vivo and hematocrit levels in each swine
      are found (r2 = 0.95-0.99). Furthermore, stepwise regression analysis of data
      from all swine shows a highly significant contribution also of other important
      parameters of blood viscosity, such as fibrinogen, total protein and temperature
      (cumulative r2 = 0.97). Determining hematocrit continuously in vivo by electrical
      resistivity measurements with a catheter in the right atrium is feasible and
      these measurements correlate significantly also with other important parameters
      of blood viscosity.

PMID- 15142604
TI  - A magnetoelastic bioaffinity-based sensor for avidin.
AB  - A magnetoelastic bioaffinity sensor coupled with biocatalytic precipitation is
      described for avidin detection. The non-specific adsorption characteristics of
      streptavidin on different functionalized sensor surfaces are examined. It is
      found that a biotinylated poly(ethylene glycol) (PEG) interface can effectively
      block non-specific adsorption of proteins. Coupled with the PEG immobilized
      sensor surface, alkaline phosphatase (AP) labeled streptavidin is used to track
      specific binding on the sensor. This mass-change-based signal is amplified by the
      accumulation on the sensor of insoluble products of 5-bromo-4-chloro-3-indolyl
      phosphate catalyzed by AP. The resulting mass loading on the sensor surface in
      turn shifts the resonance frequency of the magnetoelastic sensors, with an avidin
      detection limit of approximately 200 ng/ml.

PMID- 15142605
TI  - Depletion type floating gate p-channel MOS transistor for recording action
      potentials generated by cultured neurons.
AB  - We report the realization of electrical coupling between neurons and depletion
      type floating gate (FG) p-channel MOS transistors. The devices were realized in a
      shortened 0.5 microm CMOS technology. Increased boron implant dose was used to
      form the depletion type devices. Post-CMOS processing steps were added to expose
      the devices sensing area. The neurons are coupled to the polycrystalline silicon
      (PS) FG through 420A thermal oxide in an area which is located over the thick
      field oxide away from the transistor. The combination of coupling area pad having
      a diameter of 10 or 15 microm and sensing transistor with W/L of 50/0.5 microm
      results in capacitive coupling ratio of the neuron signal of about 0.5 together
      with relatively large transistor transconductance. The combination of the FG
      structure with a depletion type device, leads to the following advantages. (a) No
      need for dc bias between the solution in which the neurons are cultured and the
      transistor with expected consequences to the neuron as well as the silicon die
      durability. (b) The sensing area of the neuron activity is separated from the
      active area of the transistor. Thus, it is possible to design the sensing area
      and the channel area separately. (c) The channel area, which is the most
      sensitive part of the transistor, can be insulated and shielded from the ionic
      solution in which the neurons are cultured. (d) There is an option to add a
      switching transistor to the FG and use the FG also for the neuron stimulation.

PMID- 15142606
TI  - On line biomonitors used as a tool for toxicity reduction evaluation of in situ
      groundwater remediation techniques.
AB  - Success of groundwater remediation is typically controlled via snapshot analysis
      of selected chemical substances or physical parameters. Biological parameters,
      i.e. ecotoxicological assays, are rarely employed. Hence the aim of the study was
      to develop a bioassay tool, which allows an on line monitoring of contaminated
      groundwater, as well as a toxicity reduction evaluation (TRE) of different
      remediation techniques in parallel and may furthermore be used as an additional
      tool for process control to supervise remediation techniques in a real time mode.
      Parallel testing of groundwater remediation techniques was accomplished for short
      and long time periods, by using the energy dependent luminescence of the
      bacterium Vibrio fischeri as biological monitoring parameter. One data point
      every hour for each remediation technique was generated by an automated
      biomonitor. The bacteria proved to be highly sensitive to the contaminated
      groundwater and the biomonitor showed a long standing time despite the highly
      corrosive groundwater present in Bitterfeld, Germany. The bacterial biomonitor is
      demonstrated to be a valuable tool for remediation success evaluation. Dose
      response relationships were generated for the six quantitatively dominant
      groundwater contaminants (2-chlortoluene, 1,2- and 1,4-dichlorobenzene,
      monochlorobenzene, ethylenbenzene and benzene). The concentrations of individual
      volatile organic chemicals (VOCs) could not explain the observed effects in the
      bacteria. An expected mixture toxicity was calculated for the six components
      using the concept of concentration addition. The calculated EC(50) for the
      mixture was still one order of magnitude lower than the observed EC(50) of the
      actual groundwater. The results pointed out that chemical analysis of the six
      most quantitative substances alone was not able to explain the effects observed
      with the bacteria. Thus chemical analysis alone may not be an adequate tool for
      remediation success evaluation in terms of toxicity reduction.

PMID- 15142607
TI  - Labelfree fully electronic nucleic acid detection system based on a field-effect
      transistor device.
AB  - The labelfree detection of nucleic acid sequences is one of the modern attempts
      to develop quick, cheap and miniaturised hand-held devices for the future genetic
      testing in biotechnology and medical diagnostics. We present an approach to
      detect the hybridisation of DNA sequences using electrolyte-oxide-semiconductor
      field-effect transistors (EOSFETs) with micrometer dimensions. These
      semiconductor devices are sensitive to electrical charge variations that occur at
      the surface/electrolyte interface, i.e. upon hybridisation of oligonucleotides
      with complementary single-stranded (ss) oligonucleotides, which are immobilised
      on the oxide surface of the transistor gate. This method allows direct, time
      resolved and in situ detection of specific nucleic acid binding events without
      any labelling. We focus on the detection mechanism of our sensors by using
      oppositely charged polyelectrolytes (PAH and PSS) subsequently attached to the
      transistor structures. Our results indicate that the sensor output is charge
      sensitive and distance dependent from the gate surface, which pinpoints the need
      for very defined surface chemistry at the device surface. The hybridisation of
      natural 19 base-pair sequences has been successfully detected with the sensors.
      In combination with nano-transistors a PCR free detection system might be
      feasible in future.

PMID- 15142608
TI  - Calorimetric biosensors with integrated microfluidic channels.
AB  - A microfluidic device capable of measuring real-time enthalpy changes of
      biochemical reactions and thermal properties of biological fluids is presented in
      this paper. The device consists of a freestanding microthermopile integrated with
      a glass microfluidic reaction chamber. The p-type polysilicon/gold
      microthermopiles fabricated on a 2 microm thick thermally isolated membrane
      showed a sensitivity of 0.94 V/W and a thermal time constant of less than 100 ms.
      Although the device is not restricted to enzymatic reactions, in this paper
      measurements of the heat of reaction from the catalytic action of glucose
      oxidase, catalase, and urease on glucose, hydrogen peroxide, and urea,
      respectively, are reported. Reactions were performed in open air using liquid
      batch testing and in enclosed fluidic reaction chamber by continuous flow
      experiments. A sensitivity of 53.5 microV/M for glucose, 26.5 microV/M for
      hydrogen peroxide and 17 microV/M for urea was obtained. Detection limit for
      glucose in the continuous flow mode is approximately 2mM (30 pmol). The aim of
      this work is to demonstrate the potential of the integrated calorimetric
      microfluidic device for fundamental thermodynamic studies in biochemical
      reactions. Using arrays of such devices with immobilized enzymes multi-analyte
      detection can be accomplished and the effects of interferents from competing
      substrates can be compensated. This paper presents the design, fabrication and
      initial testing results from such a microthermopile-based thermal biosensor.

PMID- 15142609
TI  - Amperometric determination of lactate with novel trienzyme/poly(carbamoyl)
      sulfonate hydrogel-based sensor.
AB  - A novel trienzyme sensor for the amperometric determination of lactate was
      constructed by immobilizing salicylate hydroxylase (SHL, E.C. 1.14.13.1), l
      lactate dehydrogenase (LDH, E.C. 1.1.1.27), and pyruvate oxidase (PyOD, E.C.
      1.2.3.3) on a Clark-type oxygen electrode. The enzymes were entrapped by a
      poly(carbamoyl) sulfonate (PCS) hydrogel on a Teflon membrane. LDH catalyzes the
      specific dehydrogenation of lactate consuming NAD(+). SHL catalyzes the
      irreversible decarboxylation and the hydroxylation of salicylate in the presence
      of oxygen and NADH produced by LDH. PyOD decarboxylates pyruvate using oxygen and
      phosphate. SHL and PyOD force the equilibrium of dehydrogenation of lactate by
      LDH to the product side by consuming NADH and pyruvate, respectively. Dissolved
      oxygen acts as an essential material for both PyOD and SHL during their
      respective enzymatic reactions. Therefore, an amplified signal, caused by the
      consumptions of dissolved oxygen by the two enzymes, was observed in the
      measurement of lactate. Regeneration of cofactor was found in the trienzyme
      system. A Teflon membrane was used to fabricate the sensor in order to avoid
      interferences. The sensor has a fast response (2s) and short recovery times (2
      min). The total test time for a measurement by using this lactate sensor (4 min)
      was faster than using a commercial lactate testing kit (up to 10 min). The sensor
      has a linear range between 10 and 400 microM lactate, with a detection limit of
      4.3 microM. A good agreement (R2 = 0.9984) with a commercial lactate testing kit
      was obtained in beverage sample measurements.

PMID- 15142611
TI  - Studies of Listeria monocytogenes-antibody binding using electro-orientation.
AB  - An electro-optical (EO) approach has been used for studies of Listeria
      monocytogenes-antibody binding. The EO analyzer, which has been developed at the
      State Research Center for Applied Microbiology, Obolensk, was used as a basic
      instrument for EO measurements. AC electro-kinetic effects depend on dielectric
      properties of bioparticles, their composition, morphology, the medium, and the
      frequency of applied electrical field. Electro-orientational spectra were used
      for discrimination of bacteria before and after selective binding with
      antibodies. The measurements were performed using a discrete set of frequencies
      of the orienting electric field (10, 100, 250, and 500 kHz). During biospecific
      interactions an antibody is bound to the microorganism causing a change in the
      dielectric properties of the microorganism-antibody complex and the EO signal
      reaches its maximum at 100-200 kHz. It has been shown that the biospecific
      interactions of L. monocytogenes cells with anti-Listeria antibody in the
      presence of Escherichia coli K-12, and Azospirillum brasilense Sp7 change the EO
      signals significantly. Thus, the determination of the presence of particular
      bacteria within a mixed sample may be achieved by selection and matching of
      antibodies specific to individual bacterium types and by comparing spectra of
      bacterium in the presence and in the absence of specific antibody.

PMID- 15142610
TI  - Comparison between the surface plasmon resonance (SPR) and the quartz crystal
      microbalance (QCM) method in a structural analysis of human endothelin-1.
AB  - In this study, an automated surface plasmon resonance (SPR)-based biosensor was
      compared with a quartz crystal microbalance (QCM) biosensor. The two biosensor
      systems were used for characterizing a site-directed monoclonal antibody (mAb),
      raised against the C-terminal heptapeptide ET-1(15-21) of the human endothelin
      (ET-1). The mAb was characterized by its capacity for binding to ET-1, ET-3,
      Big.ET-1(22-38), the C-terminal (ET-1(15-21), ET-1(16-21), ET-1(17-21)), and six
      derivates of ET-1(16-21), each containing a substitution with alanine (Ala) of a
      single aminoacid from position 16-21, respectively. The mAb reacted well with ET
      1 and its fragments ET-1(15-21), ET-1(16-21), ET-1(17-21), but showed only a
      partial cross-reaction with ET-3, and did not bind human Big.ET-1(22-38). The Ala
      substitution on position 16,17, or 19 of ET-1(16-21) did not affect the antibody
      binding capacity of the hexapaptide ET-1(16-21). On the contrary, Ala
      substitution or Asp(18), Ile(20) and particularly Trp(21), inhibited its
      immunoreactivity. Thus the C-terminal represents an immunodominant epitope in ET
      1 and is important for antibody binding. The SPR and QCM response signals were
      similar in shape but differing in time scales, reflecting differences in
      detection mechanisms. With regard to the fundamental problem of comparing
      different measurement principles, we found a good correlation between results
      obtained using the BIA technology and the QCM.

PMID- 15142612
TI  - Bipolar depression: the real challenge.
AB  - This paper seeks to raise awareness of the impact and burden of bipolar
      depression and the need to improve its recognition and management in clinical
      practice. Bipolar depression is commonly misdiagnosed as unipolar depression and
      consequently, patients may receive inappropriate treatment that could potentially
      worsen symptoms. The Mood Disorder Questionnaire (MDQ) is a useful screening tool
      for identifying the range of bipolar spectrum disorders in general and
      psychiatric populations. Bipolar depression has a significant impact on patients,
      affecting work, social activities, family and friends. Current treatments for
      bipolar disorder have focused on mania, yet symptoms of bipolar depression occur
      more frequently, last longer, are more disruptive and are associated with greater
      risk of suicide than mania. In comparison with unipolar depression, bipolar
      depression is more severe, is associated with more frequent hospital visits and
      causes greater psychosocial impairment. These facts emphasise the importance of
      improving the diagnosis and treatment of bipolar depression.

PMID- 15142613
TI  - Lamotrigine: a depression mood stabiliser.
AB  - Depression mood stabilisers, which stabilise mood from below the mood baseline
      (euthymia) without inducing switch into mania or episode acceleration, are
      urgently needed for the effective treatment of bipolar depression. The
      anticonvulsant lamotrigine, recently approved as maintenance therapy for bipolar
      depression, has undergone evaluation as acute and maintenance therapy for bipolar
      disorder in several controlled clinical trials. Data from these trials suggest
      that lamotrigine is effective in the treatment and prevention of bipolar
      depression without destabilising mood. Although the majority of evidence comes
      from studies in patients with bipolar I disorder, a recent naturalistic study
      suggests that these observations may also extend to patients with bipolar II
      disorder. Lamotrigine may therefore fulfil the unmet need for an effective
      depression mood stabiliser.

PMID- 15142614
TI  - The phenotypic spectra of bipolar disorder.
AB  - Many findings that seem to be inconsistent in bipolar disorder research could be
      explained by heterogeneity of the illness and by imprecise diagnostic boundaries.
      This review of published data finds support for the existence of three main
      subtypes of bipolar disorder: (1) classical, (2) psychosis spectrum and (3)
      'characterological'. These differ with respect to clinical presentation and
      course of illness, family history and possibly long-term treatment response. For
      instance, in a series of genetic studies, lithium responders showed an episodic
      course of illness with a family history of mostly bipolar disorder. In contrast,
      responders to lamotrigine monotherapy had a rapid-cycling clinical course and
      frequent comorbid conditions, especially in the anxiety-panic disorder spectrum.
      Their relatives had elevated rates of anxiety and major depression, but not
      bipolar disorder. In summary, recognising the clinical and familial subtypes of
      bipolar disorder might lead to more targeted treatment.

PMID- 15142615
TI  - Depression mood stabilisation: novel concepts and clinical management.
AB  - No currently available mood stabiliser has equivalent efficacy in both phases of
      bipolar disorder; therefore, patients may require combination therapy with agents
      that possess complementary mood-stabilising properties. Emerging data demonstrate
      that combination therapy with lamotrigine, other mood stabilisers, and/or short
      term antidepressants or antipsychotics, is a realistic treatment option.
      Lamotrigine has a side-effect profile compatible with treatment adherence and is
      well tolerated in combination therapy. Practical guidance is provided on the use
      of lamotrigine in combination therapy. Lamotrigine represents a valuable addition
      to the current therapeutic armamentarium for bipolar disorder, allowing a
      therapeutic balance between the treatment of mania and depression.

PMID- 15142617
TI  - Capturing the adaptive mutation in yeast.
AB  - An accurate view of adaptive mutations is essential to evolutionary genetics, but
      their rarity makes them difficult to study. This can be partially overcome using
      the many tools of yeast genetics and the ability to study very large populations
      over many generations. Adaptation to laboratory environments has occurred
      primarily by chromosomal rearrangements, often involving retrotransposons and
      apparently selected for their effects on gene regulation. Estimated rates of
      adaptive mutation are on the order of 1 in 10(11) cell divisions. There remains
      great potential for the genomic study of variation within yeast species to
      contribute to our understanding of adaptive mutation.

PMID- 15142618
TI  - In vitro assays for evaluation of drug activity against Leishmania spp.
AB  - Leishmania is a parasitic protozoan which causes severe disease in humans and
      dogs. Screening of new compounds against leishmaniasis is particularly needed to
      determine the toxicity of some existing drugs and the appearance of drug
      resistant strains. Reliable and simple in vitro models are required for large
      scale initial screenings. In this review different methods for in vitro
      evaluation of drug activity against Leishmania spp. are summarized.

PMID- 15142620
TI  - Quorum sensing in the Burkholderia cepacia complex.
AB  - Quorum sensing is a cell-density-dependent regulatory mechanism which, in Gram
      negative bacteria, usually involves the production and detection of N-acyl
      homoserine lactones (HSLs). In the last four years HSL-dependent quorum sensing
      has been identified in members of the Burkholderia cepacia complex, and this mini
      review summarizes initial findings and discusses future perspectives.

PMID- 15142619
TI  - When replication travels on damaged templates: bumps and blocks in the road.
AB  - Escherichia coli can accurately replicate their genome even when it contains
      hundreds of damaged bases. In this situation, processes such as DNA repair,
      translesion DNA synthesis, and recombination all contribute to the cell's ability
      to successfully complete this task. However, under conditions when these
      reactions go awry, these same processes can result in cell lethality,
      mutagenesis, or genetic instability. In order to understand the molecular events
      that can lead this normally faithful duplication of the genome to become less
      than perfect, it is essential to define the substrates and conditions when each
      of these processes are recruited to the replication fork.

PMID- 15142621
TI  - Application of representational difference analysis to identify sequence tags
      expressed by Metarhizium anisopliae during the infection process of the tick
      Boophilus microplus cuticle.
AB  - Metarhizium anisopliae is a well-characterized biocontrol agent of a wide range
      of plagues, including insects and acari. To identify genes involved in the
      infection process, representational difference analysis was performed using cDNA
      generated from germinated conidia of M. anisopliae in the tick Boophilus
      microplus cuticle, and cDNA generated during fungal growth in glucose-rich
      medium. Sequence determination of approximately 135 clones and comparison
      analysis using public databases led to the identification of 34 sequences and 14
      expressed sequence tags with known orthologs. As expected, almost all identified
      sequences showed significant similarity to other fungal genes. The diversity of
      gene clusters found reflects the participation of several proteins in the early
      infection process of M. anisopliae in the cattle tick B. microplus.

PMID- 15142622
TI  - Transcriptional analysis of the groE and dnaK heat-shock operons of Enterococcus
      faecalis.
AB  - Enterococcus faecalis is able to survive in extremely adverse conditions, and its
      ability to resist stress is considered a key virulence attribute. Here, we
      conducted a detailed transcriptional analysis of the groE and dnaK operons of E.
      faecalis. The dnaK operon is comprised of four genes (hrcA-grpE-dnaK-dnaJ)
      preceded by two conserved CIRCE sequences. The dnaK operon is expressed from a
      sigmaA-type promoter located upstream of hrcA and multiple transcripts are
      detectable, possibly due to mRNA processing. The groE operon (groES-groEL) is
      transcribed as a single mRNA from a sigmaA-type promoter located immediately
      upstream of a CIRCE element. Induction of dnaK and groEL occurs in response to
      heat shock and exposure to NaCl, SDS and H(2)O(2).

PMID- 15142623
TI  - Interferon-gamma cooperates with Helicobacter pylori to induce iNOS-related
      apoptosis in AGS gastric adenocarcinoma cells.
AB  - Helicobacter pylori colonizes the human stomach and causes gastric disease. The
      resulting gastric damage is a multi-step process involving several molecular
      factors and different target cells. Th1 cytokines released by neutrophils and
      lymphoid cells that infiltrate gastric mucosa, nitric oxide production and
      inducible nitric oxide synthase (iNOS) are associated with immune activation and
      tissue injury. Many other molecular processes such as apoptosis, as well as
      angiogenic factors and integrins, are involved in H. pylori pathogenesis. We used
      cancer gastric cells AGS and MKN as experimental models to evaluate apoptotic
      rates, iNOS gene expression with and without the presence of interferon-gamma
      (IFN-gamma), placenta growth factor gene expression and alphav modulation. Our
      results show that AGS cells stimulated with H. pylori underwent apoptosis.
      Moreover, the addition of IFN-gamma caused a further increase in iNOS gene
      expression and in the apoptotic rates. We also found early modulation in PlGF and
      alphav expression, and noted that p53 and bax gene expression was involved in the
      apoptotic process. Taken together, these findings demonstrate that H. pylori
      employs a series of mechanisms to avoid the host defense and cause gastric mucosa
      damage. One H. pylori pathogenic mechanism for causing gastric damage is the
      induction of iNOS-dependent apoptosis that is strongly enhanced by IFN-gamma.
      Thus, data obtained indicate that Th1 cytokines such as IFN-gamma, via modulation
      of iNOS gene expression, may contribute to an increase in the pathogenicity of H.
      pylori infections.

PMID- 15142624
TI  - Glucose kinase alone cannot be responsible for carbon source regulation in
      Streptomyces peucetius var. caesius.
AB  - Using an antibiotic enrichment procedure, eight mutants of Streptomyces peucetius
      var. caesius were isolated for their sensitivity to the glucose analogue 2
      deoxyglucose (DOG), from a DOG-resistant strain (Dog(R)). These mutants (Dog(S))
      and their parent strain were examined for growth sensitivity to DOG, glucose
      kinase (Glk) activity, glucose uptake, and sensitivity to repression by glucose
      and other catabolites derived from it. No correlation was found between Glk
      levels or glucose uptake and carbon catabolite repression (CCR) in these strains.
      However, the ratio of glucose uptake to Glk activity, and thus the flux through
      glycolysis, seemed responsible for this effect. Among several products of glucose
      catabolism tested, fructose-1,6-bis-phosphate and phosphoenolpyruvate showed
      significant repression of anthracycline formation. These compounds also reduced
      anthracycline formation in a Dog(R) mutant insensitive to glucose repression. Our
      data suggest that Glk alone is not sufficient to elicit CCR in this
      microorganism, and gives the first physiological evidence supporting the
      hypothesis that some products of glucose catabolism are involved in CCR in
      Streptomyces.

PMID- 15142626
TI  - Purification and characterization of thermostable xylanase and beta-xylosidase by
      the thermophilic bacterium Bacillus thermantarcticus.
AB  - Bacillus thermantarcticus, a thermophilic bacterium isolated from Antarctic
      geothermal soil near the crater of Mount Melbourne, produced extracellular
      xylanase (1,4-beta-D-xylan xylanohydrolase; E.C. 3.2.1.8) and beta-xylosidase
      (1,4-beta-D-xylan xylohydrolase; E.C. 3.2.1.37). Each extracellular enzyme was
      separated by gel filtration with Sephacryl S-200 and further purified to
      homogeneity (119-fold for xylanase and 160-fold for beta-xylosidase). The optimum
      temperatures were 80 degrees C for xylanase at pH 5.6 and 70 degrees C for beta
      xylosidase at pH 6.0. The isoelectric points and molecular masses were 4.8 and 45
      kDa for xylanase and 4.2 and 150 kDa for beta-xylosidase, respectively. Xylanase
      was stable at 60 degrees C for 24 h, whereas it showed a half life at 70 degrees
      C of 24 h and at 80 degrees C for 50 min. beta-xylosidase activity did not
      decrease after 1 h at 60 degrees C. Km of xylanase for xylan was 1.6 mg/ml, Km of
      beta-xylosidase for p-nitrophenyl-beta-D-xylopyranoside was 0.5 mM and for o
      nitrophenyl-beta-D-xylopyranoside was 1.28 mM. The action of two enzymes on xylan
      gave only xylose.

PMID- 15142625
TI  - Pleiotropic effect of sodium arsenite on Escherichia coli.
AB  - The effects of sodium arsenite at a sub-MIC concentration (25 mg/l) upon
      different bacterial functions were studied. This compound reduced the killing
      activity of nalidixic acid, amikacin, and meropenem. It also promoted the loss of
      F'lac from bacterial hosts and increased the number of recombinants in
      conjugation and transduction experiments. Transposition of Tn9 was also enhanced
      by the salt. In addition, sodium arsenite abolished the lethal effect of
      temperature on thermosusceptible DNA synthesis mutants in a similar manner to
      that seen in an anaerobic environment. Finally at a low dose, it induced the SOS
      response, and the related production of recA-dependent enzymes was reduced as the
      sodium arsenite concentration increased. It has been suggested that arsenite
      primarily affects the uvrA gene product, influencing the other bacterial
      functions studied. The energetic depletion caused by this compound appears to
      play a role in the activity of autolytic enzymes.

PMID- 15142628
TI  - Introduction.

PMID- 15142627
TI  - Use of genes encoding cellobiohydrolase-C and topoisomerase II as targets for
      phylogenetic analysis and identification of Fusarium.
AB  - Molecular identification and phylogenetic studies rely to a large extent on rDNA
      sequence polymorphism. In the field of fungal taxonomy, despite the use of huge
      amounts of rDNA data available, some species within a given genus remain
      indistinguishable. Therefore, new target sequences need to be selected and
      validated. This is the case for Fusarium, which includes numerous species most of
      which are involved in both animal and plant pathologies. In addition to the rDNA
      fragment encompassing the internal transcribed spacers ITS1 and ITS2 and the 5.8
      S sequence, two newly characterized genes were used as molecular markers for
      Fusarium species genotyping. The cellobiohydrolase-C (cbh-C) and the
      topoisomerase II (topII) gene parts were cloned and sequenced for at least one
      isolate of each of the eleven different species of our collection. Both cbh-C and
      topII were found to be single copy genes. DNA fragments amplified by PCR in order
      to establish phylogenetic trees range from 1123 to 1157 bp for rDNA and from 327
      to 344 bp for cbh-C (this part contains one intron). The topII gene part encoding
      the carboxy-terminus of the ATP binding domain of the enzyme is constant in
      length with a value of 724 bp. PAUP-generated phylogenetic analyses based either
      on cbh-C or topII data enabled all species to be distinguished, and were more
      informative than those resulting from rDNA sequences. Furthermore, a combination
      of the three datasets enhanced the accuracy of the analyses and open up new
      possibilities for rapid molecular identification and evolution studies within the
      Fusarium genus.

PMID- 15142629
TI  - Anti-EGFR-mediated radiosensitization as a result of augmented EGFR expression.
AB  - PURPOSE: Elevated epidermal growth factor receptor (EGFR) expression has
      correlated with a poor prognosis after standard treatment of several
      malignancies. However, it is not clear whether the absolute level of EGFR
      expression affects the radiosensitizing properties of anti-EGFR treatments. A
      better understanding of this question would be helpful for the design of
      protocols that deliver these treatments. To explore this question, cells (LS174T)
      that did not display inherent anti-EGFR treatment-induced radiosensitization were
      selected for studies that could potentially enhance EGFR expression. MATERIALS
      AND METHODS: Human colon carcinoma cells (LS174T), which did not show
      radiosensitization by anti-EGFR treatments, were employed for these studies.
      (Also, these cells were not responsive to the antiproliferative effects of anti
      EGFR treatment.) Using standard transfection techniques (eukaryotic expression
      vector) as well as an adenoviral construct to enhance EGFR expression, LS174T
      cells were transduced in a manner that resulted in enhanced expression of EGFR.
      Subsequently, standard proliferation studies were performed to test the
      radiosensitizing properties of anti-EGFR treatment (an anti-EGFR monoclonal
      antibody: IMC-C225). RESULTS: Studies were undertaken to stably transfect LS174T
      cells with EGFR. The stable transfectants, LS174T.EGFR cells, were responsive to
      the antiproliferative effects of anti-EGFR treatment, in contrast to the parent
      LS174T cells. Similar results were demonstrated when the cells were infected with
      AdEGFR. Additionally, the LS174T.EGFR cells were responsive to the
      radiosensitizing properties of anti-EGFR treatment (IMC-C225), whereas the parent
      cells were not. CONCLUSIONS: Although the level of EGFR expression is of
      prognostic significance in many tumor models, the response of cells to anti-EGFR
      treatment alone, or combinations of this treatment with radiation or
      chemotherapy, depends upon many factors that are not necessarily related to the
      inherent EGFR expression of the tumor cells. However, the studies reported
      herein, demonstrate that when LS174T cells were transduced to show increased EGFR
      expression, they became responsive to the radiosensitizing properties of anti
      EGFR treatments.

PMID- 15142630
TI  - Potential role for epidermal growth factor receptor inhibitors in combined
      modality therapy for non-small-cell lung cancer.
AB  - There has been a surge of interest in the translation of discoveries in molecular
      biology into clinically relevant therapies in the field of hematology/oncology.
      The epidermal growth factor receptor (EGFR) has been a molecular target of
      significant interest and investigation, and preclinical and clinical studies
      support a role for targeted therapy in a variety of cancers, including non-small
      cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839,
      IMC-C225, and OSI-774 are the most clinically developed of these compounds.
      Interestingly, preclinical studies have demonstrated that EGFR inhibitors may
      have radiation-sensitizing properties, as well as increased cytotoxic activity in
      combination with chemotherapeutic agents, suggesting a potential role for EGFR
      inhibitors as an adjunct to the current combined-modality approach for therapy of
      Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to
      address the issue of determining the impact of the addition of EGFR inhibitors to
      the standard combined-modality regimen (chemotherapy/radiation therapy +/-
      surgery) for Stage III NSCLC. This article reviews preclinical and clinical data
      supporting the role for EGFR inhibitors alone or in combination with
      chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide
      an overview of ongoing and proposed clinical studies investigating the potential
      role for EGFR inhibitors in Stage III NSCLC.

PMID- 15142631
TI  - Review of epidermal growth factor receptor biology.
AB  - The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that
      constitutes one of four members of the erbB family of tyrosine kinase receptors.
      Binding of EGFR to its cognate ligands leads to autophosphorylation of receptor
      tyrosine kinase and subsequent activation of signal transduction pathways that
      are involved in regulating cellular proliferation, differentiation, and survival.
      Although present in normal cells, EGFR is overexpressed in a variety of tumor
      cell lines and has been associated with poor prognosis and decreased survival.
      EGFR activation also plays a role in resistance to chemotherapy and radiation
      treatment in tumor cells. Over the past two decades, much effort has been
      directed at developing anticancer agents that can interfere with EGFR activity.
      The most common pharmacologic approaches to inhibiting EGFR have been to develop
      monoclonal antibodies and small-molecule inhibitors. Monoclonal antibodies block
      ligand binding to the extracellular domain, whereas the small-molecule inhibitors
      exert their effects at the intracellular portion of the receptor to prevent
      tyrosine kinase phosphorylation and subsequent activation of signal transduction
      pathways. A number of EGFR inhibitors have been developed that can arrest tumor
      growth and, in some cases, cause tumor regression. When used in combination with
      cytotoxic treatments, chemotherapy, and radiation, EGFR inhibitors have been able
      to potentiate their anticancer activity.

PMID- 15142632
TI  - Targeted therapies for non-small-cell lung cancer: biology, rationale, and
      preclinical results from a radiation oncology perspective.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed in the majority of
      non-small-cell lung cancers (NSCLCs). This presents an opportune target for new
      treatment strategies designed to selectively interfere with the cancer cell
      growth cycle. Recent investigations into the biology of the EGFR and its
      downstream signaling pathways have reminded us of the complexity of cancer cell
      communications from the cytoplasm to the nucleus. Multiple pathways are activated
      with stimulation of the autocrine and paracrine EGFR loop, from the ras-raf-MEK
      activation of ERK 1/2 to the P13K-Akt pathway, each playing an important role in
      cancer cell survival, invasion, and angiogenesis. Preclinical studies have
      demonstrated that molecules targeting the EGFR, either through extracellular
      blockade or intracellular interference with the EGFR-associated tyrosine kinase,
      reversibly or irreversibly, inhibit cancer cell growth. Potent antitumor effects
      have been observed in human tumor xenograft models. Preclinical studies have also
      demonstrated cooperative effects when anti-EGFR agents are combined with
      radiation or chemotherapy. Many of these agents have now entered into advanced
      human clinical trials with modest dose-related toxicity despite chronic
      administration. Encouraging response rates with single-agent targeted therapy
      have been reported in heavily pretreated patients with advanced NSCLC. In
      addition, agents targeting the angiogenic pathway, which plays a key role in the
      regulation of angiogenesis, may play an important role in enhancing the efficacy
      of anti-EGFR agents. This article will focus on the biology, rationale, and
      preclinical studies with targeted anti-EGFR and antiangiogenic therapies for the
      management of NSCLC.

PMID- 15142634
TI  - Many diseases may reflect dysfunctions of autonomic balance attributable to
      evolutionary displacement.
AB  - We hypothesize that many ailments are attributable to dysfunctions of autonomic
      balance. The autonomic system is a primitive, highly-adaptive response system
      that allows differential allocation of biologic effort under varying conditions.
      The autonomic system, however, can execute a response that is inappropriate for
      the system stressor due to evolutionary displacement. Evolutionary displacement
      is a situation in which a trait that evolved as an adaptive response to certain
      conditions now faces a new set of conditions. Modern human evolution since the
      Pleistocene era is characterized by substantial evolutionary displacement,
      brought on in large part by the accelerating ability of humans to change their
      own environment. In the setting of evolutionary displacement, previously adaptive
      systems such as the autonomic system can be rendered unhelpful or even
      counterproductive. Emergence of chronic conditions, maladaptation of the trauma
      response, and extension of human lifespan are examples of evolutionary
      displacements that can induce inappropriate sympathetic bias in hosts. We
      postulate that many diseases are manifestations of this general phenomenon.
      Implications for existing and future therapeutic strategies are discussed.

PMID- 15142633
TI  - Epidermal growth factor receptor-targeted therapy with ZD1839: symptom
      improvement in non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) is a common and frequently incurable disease.
      Patients with advanced Stage IIIB and Stage IV disease, although not candidates
      for curative resection, can benefit from receiving treatment (chemotherapy and
      radiation therapy) that prolongs survival, alleviates symptoms, and/or reduces
      complications. However, these therapies are often associated with significant
      adverse events. Treatments have recently been developed to selectively target
      cancer-specific molecules and signaling pathways. By acting preferentially on
      tumor cells, these drugs leave normal cells relatively undisturbed, thereby
      limiting toxic effects and preserving the patient's quality of life. ZD1839 is
      one of a new class of targeted anticancer agents known as tyrosine kinase
      inhibitors that has demonstrated activity in the treatment of NSCLC. In clinical
      trials, ZD1839 produced responses in patients with relapsed or refractory NSCLC,
      reduced disease-related symptoms, and was associated with an improvement in
      quality of life. Results from pivotal trials with single-agent ZD1839 are
      reviewed in this article, with an emphasis on its effects on quality of life and
      symptom improvement.

PMID- 15142635
TI  - Autonomic dysregulation as a basis of cardiovascular, endocrine, and inflammatory
      disturbances associated with obstructive sleep apnea and other conditions of
      chronic hypoxia, hypercapnia, and acidosis.
AB  - Obstructive sleep apnea has traditionally been viewed as a structural disease. A
      multitude of systemic endocrine and cardiovascular abnormalities have been
      previously attributed to the prevalence of obesity in these patients. A growing
      body of clinical evidence, however, points to a relationship between sleep apnea
      and its systemic abnormalities independent of obesity. We hypothesize that this
      association is based on a maladaptive autonomic response of chemoreceptors,
      reacting to the hypoxia, hypercapnia, and acidosis of sleep apnea. The elevated
      sympathetic response triggers an inflammatory cascade that results in a myriad of
      downstream consequences including insulin resistance, hypertension, diabetes,
      atherosclerosis and metabolic syndrome. The sympathetic bias and endocrine
      disturbances may further exacerbate sleep disturbance in a potentially pernicious
      cycle. Our proposal may extend to any chronic respiratory or metabolic conditions
      that manifest hypoxia, hypercapnia, and acidosis and elicit a maladaptive
      autonomic and inflammatory response.

PMID- 15142636
TI  - Sudden death among infants and adults: companion disorders of maladaptive
      sympathetic bias.
AB  - Sudden infant death syndrome is the leading cause of death in infancy, but its
      pathophysiological mechanism has been elusive. Sudden death in adults is a common
      phenomenon, but the etiology in many cases remains unknown at autopsy. We
      hypothesize that maladaptive sympathetic bias is the explanatory mechanism that
      links many cases of sudden demise among adults and infants as companion
      syndromes. Normally, sympathetic response occurs as an adaptation to physiologic
      demands of the body through various autonomic reflex arcs such as chemoreceptors.
      Sympathetic response can become chronic and maladaptive when the normal
      sympathetic response fails to correct the precipitating physiologic trigger,
      leading to chronic activation of autonomic reflex arcs. In conditions such as
      infant sleep apnea or adult heart failure, a pernicious cycle of sympathetic bias
      may result. Chronic sympathetic bias increases susceptibility to sudden fatal
      arrhythmias, QT-related and otherwise, in the setting of an exaggerated
      adrenergic challenge. Examples of such adrenergic stressors include trauma,
      hypoxia, hypercapnia, acidosis, sleep arousal, illness, medical procedures, and
      physical activity, all of which have associations with sudden death. Our
      hypothesis may not only help explain the survival benefits of drugs such as beta
      blockers and devices such as synchronization therapy, but also portend new
      application of similar therapies for many conditions of sympathetic bias.

PMID- 15142637
TI  - Acute coronary syndromes and heart failure may reflect maladaptations of trauma
      physiology that was shaped during pre-modern evolution.
AB  - We hypothesize that the pathophysiology of many cardiovascular diseases reflects
      a maladaptation of the triad of trauma response: adrenergia, inflammation, and
      coagulation. During biologic evolution, trauma has likely been a prevailing
      factor in natural selection. Components of the trauma triad act to limit
      hemorrhage, defend wounds against microorganisms, and initiate reconstruction.
      Response pathways that enable survival after trauma confer obvious adaptive
      advantages especially if the individual goes on to reproduce. Modern humans have
      shaped their own ecologic environment in such a way that the incidence of trauma
      has waned and previously unseen pathologies have emerged. Manifestations of
      modern diet, changing lifestyles, and extended lifespan have suddenly created new
      pathologic challenges to our prehistoric physiologic system. During our
      evolutionary heritage, endothelial injury and end-organ hypoxia were likely
      exclusively associated with physical trauma and the responses of the trauma triad
      were appropriate. Today, endothelial injury is more often precipitated by
      distinctly modern stressors such as hypertension, smoking, diabetes, and
      dyslipidemia. The once-adaptive trauma response can maladaptively initiate
      dangerous, self-propelling cycles of adrenergia, inflammation, and coagulation.
      Acute coronary syndromes perhaps best exemplify this phenomenon. Congestive heart
      failure, which often ensues, can similarly be seen as a maladaptation of the
      trauma triad. Whereas end-organ hypoxia was once commonly associated with trauma,
      now hypoxia is more often attributable to distinctly modern stressors such as
      pump failure. The fluid conservation and inflammation that results from the
      trauma triad was clearly adaptive in our prehistoric past, but in congestive
      heart failure the response is maladaptive, engendering self-propelling
      exacerbations of pump failure and vascular disease. Our maladaptive trauma
      response hypothesis portends new diagnostic and therapeutic paradigms for
      cardiovascular diseases and has ramifications for many other conditions such as
      stroke, venous thrombosis, vasculitis, aortic disease, arterial disease,
      pulmonary embolism, and restenosis.

PMID- 15142638
TI  - Conditions of aging as manifestations of sympathetic bias unmasked by loss of
      parasympathetic function.
AB  - We propose a unifying hypothesis that many clinical consequences of aging are
      pleiotropic manifestations of the loss of parasympathetic function that occurs
      during post-reproductive senescence. The loss of parasympathetic function unmasks
      the baseline sympathetic bias inherent in the end-organs, resulting in the
      familiar signs of aging including tachycardia, constipation, insomnia, erectile
      dysfunction, fluid retention, and systemic inflammation. These consequences in
      turn may contribute to many of the common diseases associated with aging
      including type-2 diabetes, Alzheimer's, atherosclerosis, and cancer. Maintenance
      and restoration of parasympathetic function may enable upstream control over the
      deleterious aspects of inherent end-organ adrenergic bias.

PMID- 15142639
TI  - Nutrition, evolution and thyroid hormone levels - a link to iodine deficiency
      disorders?
AB  - An increased iodine requirement as a result of significant changes in human
      nutrition rather than a decreased environmental iodine supply is suggested to
      represent the main cause of the iodine deficiency disorders (IDD). The
      pathomechanism proposed is based on the fact that serum concentrations of thyroid
      hormones, especially of trijodothyronine (T3), are dependent on the amount of
      dietary carbohydrate. High-carbohydrate diets are associated with significantly
      higher serum T3 concentrations, compared with very low-carbohydrate diets. While
      our Paleolithic ancestors subsisted on a very low carbohydrate/high protein diet,
      the agricultural revolution about 10,000 years ago brought about a significant
      increase in dietary carbohydrate. These nutritional changes have increased T3
      levels significantly. Higher T3 levels are associated with an enhanced T3
      production and an increased iodine requirement. The higher iodine requirement
      exceeds the availability of iodine from environmental sources in many regions of
      the world, resulting in the development of IDD.

PMID- 15142640
TI  - Active sleep and its role in the prevention of apoptosis in the developing brain.
AB  - The aim of this study is to identify a possible function of Active Sleep (AS),
      also known as Rapid Eye Movement Sleep (REM) in humans, as a protective state
      during early Central Nervous System (CNS) development. Previous research suggest
      pharmacological agents that inhibit high levels of neuronal activity in the CNS
      (e.g., benzodiazepines, ethanol, and anesthetics) precipitate massive CNS
      programmed cell death (PCD), in developing mammals. AS is characterized by high
      levels of CNS activity at levels comparable to waking. AS occupies up to 75% of
      the circadian cycle in developing mammals (rodents from postnatal days 1-14 days
      (p1-p14), and humans from prenatal month seven to postnatal year one). Many
      studies have implicated AS as having an active role in the normal development of
      the visual system and have documented myriad behavioral anomalies as a result of
      AS deprivation. Reduced adult brain mass has also been observed after AS
      deprivation in developing rats during this period, however, no study to date has
      documented this process as it occurs (i.e., the cellular mechanisms that result
      in behavioral anomalies or reduced adult brain mass). The purpose of this study
      is to begin documentation of this process by utilizing histological techniques
      that identify the PCD process, if it occurs, after acute and prolonged AS
      deprivation in rats from ages p7 to p14 (a time of active synaptogenesis). Our
      methodology includes utilization of the alpha2-adrenergic receptor agonist
      clonidine, to deprive rat pups of AS at ages varying from p7 to p14. Pilot data
      from our laboratory has shown that an acute exposure to clonidine significantly
      reduces time spent in AS. The animals that were AS deprived also showed a
      statistically significant decrease in brain mass and have stained positively for
      PCD. If our hypotheses are correct, this research will have major implications
      with regard to determining the function(s) of REM sleep.

PMID- 15142641
TI  - Inverse trend between estimated worldwide frequency of major cancers and inferred
      infectious burdens of populations: possible role of adaptive immune system.
AB  - Regions of the world subjected to heavy infectious burdens seem to show lower
      incidence of cancer. The index of infectious burden in this study has been chosen
      to be poverty, i.e., low GDP, high infantile mortality, poor hygienic conditions,
      inaccessibility to modern medical infra-structures, etc. When estimates of
      observed cancer incidence is plotted against the GDP of 24 regions of the world,
      a trend line is obtained: low GDP (a proxy for high infectious burden) tends to
      be associated with low incidence of cancer whereas high GDP values herald higher
      cancer occurrences. Similarly, countries with high infantile mortality rates tend
      to have a lower incidence of cancer and vice versa. The data are explained in
      terms of the so-called "hygiene hypothesis": frequent infectious onslaughts,
      especially in childhood, challenge the immune system and build a strong adaptive
      immune system and immunological memory which prepare the body to tackle further
      battles down the line, such as cancer. Within this framework, the role of other
      factors such as diet, selenium, hardness of water, etc. in the aetiology of
      cancer is also briefly examined. For rigorous verification of this observation,
      age-adjusted cancer incidence rates for various countries must be used even
      though such data are not available for all the countries examined here [Bulletin
      of World Health Organization 62(2) (1984) 163]; where data are available [Age
      adjusted death rates for cancer for selected sites (A classification) in 51
      countries in 1974, Segi Institute of Cancer Epidemiology, Nagoya, Japan (Feb.
      1979); Global Geocancerology, Churchill Livingstone, New York, 1986], the same
      trend is also observed for the age-adjusted cancer death rates, which may be used
      as an index of age-adjusted cancer incidence, subject to qualifications discussed
      in the text.

PMID- 15142642
TI  - Bacteriophages: antibacterials with a future?
AB  - The hypothesis as to whether a benign species of bacteria could kill a virulent
      kind has to this point been untested. Recently it was shown that in the
      macrophage, bacteriophages, when properly introduced through a nonvirulent
      microbe, had a killing rate for virulent AIDS Mycobacterium tuberculosis and
      Mycobacterium avium far in excess of modern day antibiotics. The study in effect
      brought a natural phenomena, lysogeny, whereby one bacterial colony kills another
      thru phage weaponry, to bear in the conquest of hard-to-kill, antibiotic
      resistant pathogens. This killing occurred intracellularly, within the white
      blood cell using Mycobacterium smegmatis, a benign bacterial species found
      generally in smegma secretions from human genitalia as well as soil, dust and
      water, and first identified in 1884. The subsequent treatment of M. avium
      infected, as well as M. tuberculosis-infected RAW 264.7 macrophages, with M.
      smegmatis transiently infected with TM4 resulted in a unexpectedly large time-
      and titer-dependent reduction in the number of viable intracellular bacilli. In
      addition, the M. smegmatis vacuole harboring TM4 fused with the M. avium vacuole
      in macrophages. These results suggested a potentially novel concept to kill
      intracellular pathogenic bacteria and warrant future development.

PMID- 15142643
TI  - Could rheumatoid arthritis result from an abnormal T cell response towards
      lubricin/superficial zone protein?
AB  - The lack of some suppressor T cells (including TCD4+CD25+(high) positively
      selected first in thymic medulla) specific to a restricted set of autoantigens
      may be the common link between all patterns of rheumatoid arthritis. In other
      words, instead of a 'peak' of TCD4+ effector T cells common to all patients with
      rheumatoid arthritis (which has so far never been demonstrated), a 'hole' in
      TCD4+CD25+(high) responses towards a limited set of autoantigens responsible for
      the normal maintenance of tolerance within the joints may be shared by many
      patients with rheumatoid arthritis. The hallmark of this disorder is the
      involvement of tissues subjected to friction stress bathed in a lubricating fluid
      (rheumatoid nodules and bursae, tendinous sheaths, pleura, pericardium, sclera,
      and joints covered by hyaline cartilage). Consequently, autoantigens shared by
      all forementioned places may be better candidates than autoantigens restricted to
      the hyaline cartilage (like collagen II). Tenosynovitis, bursitis and rheumatoid
      nodules can herald rheumatoid arthritis, and rheumatoid pericarditis is very
      frequent at the histological level. Lubricin and superficial zone protein (SZP),
      which are closely related products of the megacaryocyte stimulating factor (MSF)
      gene, are among the best candidate autoantigens for such a positive selection of
      suppressor T cells. Lubricin is responsible for most of the lubricating
      properties of synovial fluid, and SZP (expressed by the superficial articular
      chondrocytes from diarthrodial cartilages and lining cells of synovial villi)
      also shares lubricating and cytoprotective properties. Moreover, the expression
      of lubricin is very probable in pericardium and pleura, and can be induced by
      friction stress. Although this mucinous glycoprotein may already share close
      similarities at the antigenic levels with mucins previously demonstrated in
      Hassall's corpuscles of the thymus, evidence for the ectopic expression of
      lubricin/SZP within normal human thymus may further support this hypothesis. The
      prenatal positive selection within the thymus of a functional pool of
      TCD4+CD25+(high) clones specific for most peripheral tissues is critical (at
      least in mice) for the quality of tolerance for the rest of the organism's
      lifespan. Therefore, a poor expression of lubricin/SZP early in life within the
      human thymus may also favour a lack of suppressor T cells specific to tissues
      bathed with synovial fluid, i.e. the onset of rheumatoid arthritis later on in
      life. As studies of human thymus long before the onset of rheumatoid arthritis
      are hampered for obvious reasons, studies of murine thymus could be a first step.
      In as much as the human counterpart of lubricin is expressed in the thymic
      medulla of mice, the generation of knocked-out mice for its expression within the
      thymus could be one of the best models to test the above hypothesis. The
      stimulation of TCD4+CD25+(high) clones specific for immunodominant epitopes from
      the joints/synovial fluid (belonging perhaps to lubricin or SZP) could help
      restore a normal balance between effector T cells and suppressor T cells in
      rheumatoid arthritis patients.

PMID- 15142644
TI  - Do T lymphocytes correlate danger signals to antigen?
AB  - When a cell is infected by a virus, or becomes transformed into a malignant
      state, it presents clues to its disease on the outer surface of its membrane.
      Such clues include peptide fragments of proteins produced inside the cell; when
      the cell is infected by a virus, viral peptides, as well as the cell's normal
      peptides, are displayed on the cell's membrane as potential antigens. Infected
      and malignant cells also externally present special molecules that ligate NKG2D
      receptors on immune cells. When patrolling T lymphocytes detect the presence of
      both their cognate peptide antigen and NKG2D ligands on one target, they
      proliferate and increasingly kill other cognate target cells. The danger model of
      immunity recognizes NKG2D ligands as stimulators of T cell cytotoxicity, but
      heretofore could not explain how T cells specific to normal peptides typical of
      healthy host cells outside the thymus, could avoid activation by danger signals
      on diseased cells. The problem is that T cells specific to host-peptides are also
      stimulated when those peptides are by chance also displayed on diseased cells
      displaying NKG2D ligands. However, if T cells predicated their cytotoxicity not
      only on the presence of their cognate antigen found in conjunction with danger
      signals, but also on the absence of their cognate antigen on cells not presenting
      danger signals, then only T cells specific for disease antigens would become
      activated. Since Fas display is correlated with viral or malignant
      transformation, it may be a danger-signal like NKG2D ligands. T cells which
      encounter Fas on malignant, cognate cells, increasingly bind Fas on healthy
      bystander cells not displaying cognate antigens. Perhaps such healthy bystander
      cells provide T cells with reference-levels of danger-signals for local tissue
      cells, allowing T cells to select between tolerance and cytotoxic reaction to
      their cognate antigen, as they circulate in the periphery. This paper will
      analyze cytotoxicity assays that show that T cells challenge syngeneic, non
      cognate bystanders with Fas ligand (FasL), and why syngeny is a requirement for
      danger-reference cells. Some heretofore unexplained effects of superantigens will
      be suggested to be due to their obstruction of reference-target detection. This
      paper will also suggest that established tumors often evolve a subpopulation of
      high-danger-signal, low tumor-antigen cells that protect the tumor against T
      cells; that characteristics of dendritic cells (DC) complement the danger sensing
      of T cells; and that DC may also use quantitatively comparative, self
      referential, danger-correlation measurements to recognize transformed cells
      interspersed among healthy host tissue cells.

PMID- 15142645
TI  - Gene silencing: a possible molecular mechanism in remission of affective
      disorder.
AB  - Based upon a case report, the hypothesis is proposed that a virus infection could
      be responsible for remission of affective disease by causing gene silencing. A
      farmer of 59 had been suffering from a therapy resistant depressive episode over
      many months. His depressive illness seemed primarily biogenetically determined.
      Because of acute suicidality clinical treatment and observation became necessary.
      After six weeks of unsuccessful psychiatric treatment the patient caught a severe
      virus infection causing pneumonia and myocarditis. The physical treatment showed
      up to be difficult, but finally managed to cope with the virus infection.
      Remarkably, parallel to the decrease of physical symptoms also the mood was
      markedly elevated towards a full remission. At that time the patient was no
      longer under antidepressant medication. Many viruses have a genetic blueprint
      made from RNA, rather than DNA. When they infect a cell, double-stranded copies
      (double-stranded RNA, dsRNA) of their genetic material are produced. In response,
      the RNA interference (RNAi) pathway of the infected cell is activated. The enzyme
      Dicer first chops viral dsRNA into small segments of 21-25 basepairs in length,
      termed short interfering RNAs (siRNAs) and these siRNAs are used to identify
      intact viral RNA and to mark it for destruction. When an endogenous gene is
      activated, its sequence is read to produce messenger RNA (mRNA), which contains
      the information necessary to produce a particular protein, and improper
      expression of an endogenous gene could cause affective disorder in a patient.
      Therefore one would expect that if such a patient were infected by a virus that
      contained a sequence similar to the improperly expressed endogenous gene, the
      patient's anti-viral response would inadvertently reduce expression of the gene
      causing affective disorder. If mutations in genes responsible for affective
      disorders are identified and they turn out to cause over-expression of a
      particular gene, gene silencing could be an alternative therapeutic tool,
      especially for therapy-resistant severe depression. The therapy could involve
      introducing dsRNA either as synthetic RNA, or by infecting the patient with a
      recombinant virus containing sequence from the gene whose expression must be
      reduced.

PMID- 15142646
TI  - Proposed role for small cytoplasmic vesicles in cytokine secretion by mouse
      macrophages.
AB  - This report represents an extension of a prior report hypothesizing that
      cytokines in mouse macrophages are secreted by a morphologic array of small
      vesicles which fuse with the cell membrane and which originate in the Golgi
      complex [Med Hypoth 53 (1999) 107]. The Golgi complex in macrophages is
      distinguished by a characteristically multicentric configuration and shows
      budding of vesicles from the closely approximated tips of the lamellae. The
      location of small vesicles which extend from the Golgi complex to the cell
      membrane supports the hypothesis that there is one type of vesicle which fuses
      with the cell membrane and secretes its content of cytokines. The other type of
      vesicle has been shown to fuse with pinocytic vacuoles to form hydrolase positive
      cytoplasmic granules. Consideration of cytokines produced by macrophages will
      help to clarify the immunologic functions of these cells.

PMID- 15142647
TI  - The malignant transformation event as a clonal transformation of apoptosis to
      anti-apoptosis pathways and of cell cycle dynamics.
AB  - Anti-apoptosis, as a more vital aspect of a whole series of progressive steps in
      carcinogenesis, would appear primarily a phenomenon of variable
      nonresponsiveness. Programmed cell death, in addition, would appear to affect the
      individual cell as attributes also of an integral field phenomenon constituted by
      clones of tumor cells that grow, proliferate and spread. Various modes of
      development of anti-apoptosis subsequently involving the development of genetic
      abnormalities would possibly account for transformation as a neoplastic
      phenomenon. It is in terms of such pathways as telomeric length preservation, of
      anti-apoptosis as failed activation of apoptosis, and of failed DNA binding
      events that clonally selected tumor cells would tend to inherently progress to
      higher grade and stage and to spread systemically. Moreover, clonal and field
      events would possibly influence in their turn individual cell cyclical activity
      and programmed cell pathways in neoplastic transformation. Anti-apoptosis would
      constitute, in fact, a predicted system of pathways that switch from apoptosis as
      an essential pathway in malignant transformation. Angiogenesis, as a full series
      of cascade events of a paracrine/autocrine nature, would also participate with
      anti-apoptosis in a tumor cell cycle transformation that is self-amplifying.
      Given different modes of how apoptosis would convert to anti-apoptosis in
      tumorigenesis, perhaps abnormal cell cycle dynamics might also contribute to the
      evolving nature of such neoplastic transformation.

PMID- 15142648
TI  - Is RNA-laden p24 capsid protein a vector for HIV?
AB  - The consensus HIV infection pathway, although well supported by abundant
      experimental evidence, fails to account for infection of cells (e.g., neurons)
      that lack CD4 and/or coreceptors. We present the hypothesis that p24 capsid
      protein laden with RNA may be an alternative virulent agent. A novel mechanism of
      HIV infection may involve binding of the capsid with membrane receptors, followed
      by internalization of the capsid-receptor complex. This new pathway suggests
      novel strategies for antiviral pharmacotherapy.

PMID- 15142649
TI  - Systemic lupus erythematosus: a combined deficiency disease.
AB  - To date, the pathogenesis of systemic lupus erythematosus (SLE) remains unclear.
      By critically analyzing clinical facts and laboratory data, a hypothesis is
      proposed: drug-induced lupus erythematosus (DILE) is linked to a deficiency in
      Coenzyme A (CoA) that is secondary to a deficiency in pantothenic acid. This
      hypothesis is used to explain the high incidence of SLE in females, the role of
      sex hormones in this disease and the mechanism underlying a flare. The actions of
      anti-malarials and steroids are also discussed. The protean clinical presentation
      of SLE is attributed to co-existing deficiencies of dietary factors in addition
      to pantothenic acid. Contributing factors to these deficiencies may include
      increased nutritional requirements resulting from gene mutations. Treatment is
      replacement therapy with doses of pantothenic acid that is hundreds of times
      higher than that of the Dietary Reference Intake (DRI) and other vitamins. Using
      this method, 12 SLE females were studied with promising results.

PMID- 15142650
TI  - Can chronic increased intracranial pressure or exposure to repetitive
      intermittent intracranial pressure elevations raise your risk for Alzheimer's
      disease?
AB  - Over a decade ago, I formulated the hypothesis that cumulative effects of
      exposure to high intracranial pressure (ICP) may contribute to the development of
      Alzheimer's disease (AD), though not necessarily in an exclusive way. In addition
      to individual ICP characteristics (high 'physiological' ICP) and diseases causing
      ICP elevation, various activities with significant Valsalva effort, such as
      weightlifting and wind instrument playing, can generate very high ICPs. Recent
      studies of normal-pressure hydrocephalus (NPH), glaucoma and Alzheimer's disease
      provide supportive evidence for this hypothesis. A number of studies have shown a
      high incidence of AD related lesions in patients with NPH, which is known to be
      associated with prolonged elevation of ICP in a majority of cases. In both NPH
      and AD, an important decrease in cerebrospinal fluid (CSF) production was
      calculated. According to researchers in the US, the resulting CSF stagnation with
      impaired clearance and accumulation of neurotoxic substances may play an
      important role in the onset and progression of AD. They tested the hypothesis
      that improving CSF turnover by means of an investigational low-flow
      ventriculoperitoneal shunt will delay the progression of dementia in patients
      with Alzheimer's disease. With regard to the observed decrease in CSF production
      in patients suffering from NPH, it was postulated that chronic increased ICP
      causes downregulation of CSF production. It is hypothesized here that repetitive
      intermittent ICP elevations also may lead to downregulation of CSF production due
      to long-term cumulative effects. If the latter proves to be true, then both
      chronic increased ICP and repeated exposures to increased ICP (e.g., repetitive
      Valsalva maneuvers) may cause a similar cascade of CSF circulatory failure events
      leading to AD over time. Furthermore, AD may be causally related to increased ICP
      through other pathomechanisms. Additional supportive evidence for the role of a
      pressure factor in the pathogenesis of AD comes from studies concerning glaucoma.
      Elevated intraocular pressure (IOP) is a hallmark of glaucoma. Recently,
      similarities in pathophysiology between glaucoma and AD have been noted, with
      increased processing of amyloid precursor protein (APP) and up-regulation of beta
      amyloid protein expression in retinal ganglion cells (RGCs). Given this link
      between AD and glaucoma, evidence for a causal relationship between repetitive
      intermittent ICP elevations and AD is gained from research indicating that high
      resistance wind instrument playing raises IOP and may result in glaucomatous
      damage. To test the validity of the hypothesis that exposure to repetitive but
      nonsustained ICP elevations may predispose to AD a non-invasive, epidemiological
      study is proposed in this paper.

PMID- 15142651
TI  - Alkali ingestion predisposes to developing giant mid-esophageal pulsion
      diverticulum - a report of a medical rarity.
AB  - Pulsion diverticulae of the mid-esophagus with unknown etiology are usually
      asymptomatic and therefore considered incidental findings on chest X-rays, barium
      swallows, or endoscopic procedures. Diagnosis is often delayed due to the rarity
      of clinical symptoms. The clinical, radiological, etiological and surgical
      features in a patient with extraordinary symptomatic giant mid-esophageal pulsion
      diverticulum with history of alkali ingestion are presented here. Alkali injury
      may yield asymptomatic strictures and/or acquired weaknesses of the esophageal
      wall, both of which are known to lead to the formation of this giant malady.
      Putative pathomechanism and suggested therapy including diverticulectomy is
      proposed in this communication.

PMID- 15142652
TI  - Aerobic exercise: a potential therapeutic intervention for patients with liver
      disease.
AB  - Fatigue is a symptom of liver disease. Indirect evidence suggests that this type
      of fatigue is centrally mediated. Non-alcoholic steatohepatitis (NASH), which may
      lead to cirrhosis, is associated with insulin resistance. An activated
      hypothalamic pituitary adrenal axis results in increased secretion of cortisol
      releasing hormone, cortisol and catecholamines. Prolonged exposure to high levels
      of cortisol is associated with insulin resistance, as exemplified by the
      metabolic syndrome. Accumulation in visceral fat is an independent factor
      associated with insulin resistance. Central (visceral) fat is less sensitive to
      insulin than the rest of body fat and the central nervous system and not
      peripheral insulin, appears to regulate lipolysis in visceral fat by, at least in
      part, adrenergic mechanisms. Aerobic training has documented beneficial effects
      on mental health and fatigue secondary to chronic illness. In addition, aerobic
      training increases insulin sensitivity. Thus, aerobic training may decrease
      fatigue in liver disease and improve NASH.

PMID- 15142653
TI  - Hypocalcemic effect of zoledronic acid or other bisphosphonates may contribute to
      their antiangiogenic properties.
AB  - Bisphosphonates, effectively used for metastatic bone disease and hypercalcemia,
      may evidentially have antiangiogenic properties. However, mechanism(s) of
      antiangiogenic effects of bisphosphonates are not fully understood. Their most
      pronounced effect is on metabolism of calcium, which is a main point of
      intersection for many distinct molecular signaling pathways that promote and
      modulate angiogenesis. An elevation of Ca(2+) plays a role in the mitogenic and
      secretory effects of growth factors. Some preclinical clues imply that
      antiangiogenic effects of bisphosphonates are related to its well-known
      hypocalcemic activity. Consequently, it may not be right to routinely recommend
      vitamin D and calcium supplementation to correct hypocalcemia unless it is
      symptomatic.

PMID- 15142654
TI  - A possible interdependency between the wavy path of enamel rods, distances of
      Retzius lines, and mitotic activity at the cervical loop in human teeth: a
      hypothesis.
AB  - In human enamel, the enamel rods do not run straight in most regions. Instead,
      they obtain an undulated path. The diameter of the enamel rods remains constant
      all the way, and a wavy pattern is necessary to produce the volume of the enamel
      mantle. It is not understood, how this undulated migration of ameloblasts is
      created. Considerations are presented to explain causal interdependencies between
      the wavy path of the enamel rods, unequal growth of the cervical loop cells and
      unequal distances of the striae of Retzius. To test these considerations, further
      research must record mitotic activity at the cervical loop during the stages of
      dental development. The distances of Retzius lines must be measured at different
      spots all over the whole enamel mantle, preferably in 3D. As a result, knowledge
      of the interdependency between the inner structure and the outer form of each
      tooth crown will lead to an understanding of tooth form and occlusion.

PMID- 15142655
TI  - beta-carotene and oxidative desaturation of fatty acids: a plausible explanation
      of the conflicting responses of coronary heart disease to beta-carotene?
AB  - Studies of the desaturation of saturated fatty acids in animals may help explain
      conflicting reports of the response of coronary heart disease (CHD) to beta
      carotene in humans. A negative relationship exists between desaturation and
      adipose beta-carotene in cattle when they consume different quantities of beta
      carotene. Opposing this finding, however, is a positive relationship between
      desaturation and adipose beta-carotene when cattle are fed the same quantity of
      beta-carotene. The reason for this apparent contradiction appears to be due to
      differences in consumption, or variability in the metabolism of beta-carotene.
      Animals that efficiently metabolize beta-carotene to vitamin A have low
      desaturation but high antioxidant potential. These results in animals show some
      similarity between the consumption of the antioxidant beta-carotene and the risk
      of coronary heart disease where the oxidation of low-density lipoproteins (LDL)
      is believed to play a role in the development of atherosclerotic plaque. Genetic
      differences in carotenoid metabolism in humans, similar to those in animals,
      would assist in explaining differences in lipoprotein oxidation in humans and
      variation in the risk of coronary heart disease.

PMID- 15142656
TI  - The androgen receptor of the prostate plasma membrane - an hypothesis.
AB  - The hypothesis that the prostatic plasma membrane sodium pump apparatus functions
      as a non-genomic androgen receptor is based upon a number of its properties: (1)
      Androgen enhances the uptake of K(+) into minced rat prostate. (2) Ouabain, a
      specific inhibitor of Na/K-ATPase activity, strongly opposes the androgenic
      effect. (3) In non-genomic microsomes, ouabain sensitivity of the enzyme is
      enhanced by androgen. (4) Kinetic studies show that androgen significantly
      increases Vmax, Km and energy of activation of the enzyme. (5) Enzyme, treated
      with [gamma-(32)P]-ATP and then subjected to SDS-PAGE electrophoresis, binds only
      to its alpha-subunit, but, if treated with [(3)H]-DHT, shows isotope binding to
      the beta-subunit. (6) [(3)H]-ouabain binding to androgenized enzyme is 5.5 times
      greater than to the non-androgenized enzyme. (7) Treatment of the enzyme with 10(
      9) M DHT enhances by 40% the binding of the ouabain derivative, anthroyl ouabain
      (AO). (8) Fluorescent spectra appears to show that, upon phosphorylation of the
      androgenized enzyme, there is a 14% approximation of the two subunits to each
      other. (9) Except for neuroepithelium, only the epithelium of the prostate has
      apically located Na/K-ATPase. Preliminary work in other labs suggests that the
      beta-subunit of the Na/K-ATPase may be required for establishing the polarity of
      some epithelial cells.

PMID- 15142657
TI  - Experimentally gained insight - based proposal apropos the treatment of
      osteonecrosis of the femoral head.
AB  - An impeded blood flow through the femoral head is incriminated in the
      etiopathogenesis of osteonecrosis of the femoral head. The disorder is either
      primary (idiopathic avascular osteonecrosis) or secondary to one condition or
      another, say, corticosteroid medication, fracture of the neck, coagulation
      defects, physical or thermal damage, storage disorders, alcoholism, and
      infectious, autoimmune as also marrow infiltrating diseases. In the wake of the
      necrosis, several mediators are released in increased amounts, prime among which
      is the vascular endothelial growth factor. The intermediates recruit endothelial
      progenitor cells, macrophages, osteoclasts, fibroblasts, and osteoblasts, which,
      pervading throughout the necrotic areas, initiate the reparative processes. The
      dead, soft and hard tissular debris is substituted by fibrous - later on by
      hematopoietic-fatty tissue - and bone. The newly formed, appositional and
      intramembranous bone is deficient in its mechanical properties. The ordinary load
      carrying functions suffice to deform these weakened femoral heads so that
      osteoarthritic changes develop. Considering contemporary assumptions of the
      causes of osteonecrosis, oxygenation, revascularization, and core decompression
      are the realistic therapeutic interventions. Necrosis of rats' femoral heads is
      studied as a model of osteonecrosis in both adults and children. In view of
      rodents' lifelong persisting physeal cartilage, vascular deprivation-induced
      osteonecrosis in rats mimics children's Perthes disease. The experimental model,
      which is well suited to test treatment modalities, has been used to investigate
      the effects of exposure to hyperbaric oxygen with and without non-weight bearing,
      medication of enoxaparin, and creation of an intraosseous conduit on the
      remodeling of the avascular necrotic femoral head. Intriguingly, the shape of
      treated rats' femoral heads is disfigured to a greater degree than that of
      untreated animals. This is most likely due to the reduced yield strength and
      elastic modulus as well as the raised strain-to-failure of the recently formed
      bone making up the post-necrotic femoral heads. It follows that expedited
      osteogenesis is, counter intuition, detrimental to maintaining the hemispherical
      shape of the femoral head, and thus to an articulation with congruent load
      bearing surfaces. If this is indeed the case, the remodeling of the necrotic
      femoral head should be delayed, rather than sped up, as the present day paradigm
      would have it. Bearing in mind that the dead osseous structures keep their
      mechanical attributes for quite a while, a slowed down new bone formation would
      favor the gradual replacement of the necrotic by living bone. Therefore,
      management of the adult patients with osteonecrosis and children with Perthes
      disease should focus on a slowly progressive substitution so that the decline of
      the bone's mechanical properties is kept to a minimum. One viable therapeutic
      mode is a medication of inhibitors of the vascular endothelial growth factor.

PMID- 15142658
TI  - A basis of the acanthocytosis in inherited and acquired disorders.
AB  - Acanthocytosis refers to the transformation of the normal biconcave disc
      erythrocyte into one with a few irregularly shaped external projections
      distributed unevenly at its membrane surface. It is associated with a variety of
      inherited and acquired disorders. A relationship between the acanthocytosis in
      chorea-acanthocytosis and an alteration of Band 3, the anion exchange protein,
      has been previously suggested. We have previously proposed a mechanism of
      erythrocyte shape control in which decrease and increase of the ratio of the
      outward-facing (Band 3(o)) and inward-facing (Band 3(i)) conformations of Band 3
      contracts and relaxes the membrane skeleton, thus promoting echinocytosis and
      stomatocytosis, respectively. The equilibrium Band 3(o)/Band 3(i) ratio is
      determined by the Donnan equilibrium ratio of anions and protons, increasing with
      the increase of the Donnan ratio. Based on the evidence suggesting that the
      acanthocyte and echinocyte are interrelated, the mechanism could explain by a
      decrease of the Donnan ratio the occurrence of acanthocytes in pyruvate kinase
      and pyrimidine 5'-nucleotidase deficiencies, dehydrated hereditary
      stomatocytocytosis, In(Lu) phenotype, chorea-acanthocytosis, and McLeod
      phenotype. Consistent with the proposed mechanism indicating that the membrane
      skeleton is an important determinant of the erythrocyte shape, is the alteration
      of its conformation in chorea-acanthocytosis, McLeod phenotype and Fanconi's
      anemia. In agreement with the proposed mechanism indicating that Band 3
      conformation controls the erythrocyte shape are the occurrence of an
      acanthocytosis in individuals expressing the rare Band 3 HT variant and of
      alterations of Band 3 properties in chorea-acanthocytosis and In(Lu) phenotype.
      The observations that the lipid composition or organization are normal in chorea
      acanthocytosis and McLeod phenotype are supportive of the proposed mechanism
      since it postulates that the lipid bilayer has a secondary role in determining
      the erythrocyte shape. The acanthocytoses in alcoholic cirrhosis and
      abetalipoproteinemia are accompanied by significant increases of the cholesterol
      level and of the ratio of sphingomyelin and glycerophospholipids, respectively.
      However, they could occur by a change of the Band 3 conformation since
      cholesterol binds specifically to Band 3 and inhibits its anion transport
      activity, and that sphingomyelin potentiates this inhibition. Thus, the
      acanthocytosis could involve an alteration of the Band 3 conformation.

PMID- 15142659
TI  - Is autism a disorder of fatty acid metabolism? Possible dysfunction of
      mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase.
AB  - Long chain acyl-CoA dehydrogenase (LCAD) has recently been shown to be the
      mitochondrial enzyme responsible for the beta-oxidation of branched chain and
      unsaturated fatty acids [Biochim. Biophys. Acta 1393 (1998) 35; Biochim. Biophys.
      Acta 1485 (2000) 121]. Whilst disorders of short, medium and very long chain acyl
      dehydrogenases are known, there is no known disorder of LCAD deficiency in
      humans. Experimental LCAD deficiency in mice shows an acyl-carnitine profile with
      prominent elevations of unsaturated fatty acid metabolites C14:1 and C14:2 [Hum.
      Mol. Genet. 10 (2001) 2069]. A child with autism whose acyl-carnitine profile
      also shows these abnormalities is presented, and it is hypothesized that the
      child may have LCAD deficiency. Additional metabolic abnormalities seen in this
      patient include alterations of TCA energy production, ammonia detoxification,
      reduced synthesis of omega-3 DHA, and abnormal cholesterol metabolism. These
      metabolic changes are also seen as secondary abnormalities in dysfunction of
      fatty acid beta-oxidation, and have also been reported in autism. It is
      hypothesized that LCAD deficiency may be a cause of autism. Similarities between
      metabolic disturbances in autism, and those of disorders of fatty acid beta
      oxidation are discussed.

PMID- 15142660
TI  - Obesity and depression: same disease, different names?
AB  - Obesity is a major public health problem, which occurs in epidemic proportions.
      Our understanding of the systems of the brain related to energy balance has
      increased over the last decade. As a result, drugs most commonly used today in
      the management of obesity have their primary effect in modulating the balance
      between monoaminergic neurotransmitters, among other serotonin. Serotonin is
      believed to be involved in the complex process of integrating physiological and
      behavioral systems geared towards energy balance. However, gradual weight gain
      seen in most people suggests that the regulatory system may not be sufficient
      under all circumstances. An insufficient serotoninergic neuronal function in the
      central nervous system has been shown in many studies to occur in patents with
      depression. In such serotonin-deficient patients, treatment with drugs increasing
      the concentration of serotonin at serotoninergic synapses gives a favorable
      clinical response. Taken together, this suggests to a certain extent a common
      pathophysiology between obesity and depression. Literature spanning several
      decades has addressed the relationship among obesity and depression. However,
      obesity and depression research have evolved as two independent disciplines,
      which rarely or never overlap. In this paper, we propose the notion that obesity
      and depression may represent different manifestations of the same disease process
      - Janus faces of the modern society.

PMID- 15142661
TI  - Cultural evolution as a possible triggering or causative factor of common
      baldness.
AB  - Common baldness (alopecia) increasingly affects a higher number of individuals at
      earlier ages, independently of gender. One of the reasons could be lack of
      knowledge concerning its etiology. The human being has evolved to become a naked
      monkey, although there is no apparent reason to continue the evolutionary process
      up to becoming a bald monkey. According to this theory, common baldness is a
      degenerative process derived from certain inadequate cultural practices, such as
      excessive hair cutting or certain types of haircuts that prevent contact among
      hairs themselves and limit outside contact in ways that would alleviate balding.
      Blocking the flow of sebum towards the base of the hair follicle - and so
      interfering with the arrival of the stem cells to the dermal papilla with
      consequent hair miniaturization - ends up being the first negative physiological
      effect derived from certain cultural habits. As time goes by, other mechanisms
      become altered, which leads to a less and less reversibility of the process.

PMID- 15142662
TI  - A general model for genetic regulation of turnover of glycosaminoglycans suggests
      a possible procedure for prediction of severity and clinical progress of
      mucopolysaccharidoses.
AB  - Mucopolysaccharidoses are rare genetic diseases from the group of lysosomal
      storage disorders caused by deficiency of enzymes involved in degradation of
      mucopolysaccharides (glycosaminoglycans, GAGs). Within each
      mucopolysaccharidosis, there is a continuous spectrum of clinical features from
      the very severe to the more mildly affected individuals. Surprisingly, in most
      cases, it is not possible to predict severity and clinical progress (i.e., the
      natural history) of the disease on the basis of detection of particular mutations
      or residual activity of the deficient enzyme. In this article, the reasons for
      such an unexpected difficulty are discussed. A model for the correlation between
      residual activity of a lysosomal enzyme and the turnover rate of its substrate(s)
      has been proposed previously by others, however, in that model it was assumed
      that substrate concentration in the lysosome is not regulated, thus the residual
      activity of a hydrolase would be the only determinant of the rate of substrate
      accumulation. On the other hand, both a general model for genetic regulation of
      turnover of GAGs and results of very recent studies strongly suggest that
      expression of genes coding for enzymes involved in GAG synthesis is precisely
      regulated and may vary between individuals. Therefore, we propose that apart from
      measurement of residual activity of the enzyme involved in degradation of GAGs,
      the efficiency of synthesis of these compounds should also be estimated. If the
      hypothesis presented in this article is true, the ratio of the synthesis of
      glycosaminoglycans to the residual activity of the deficient enzyme should be of
      considerable prognostic value.

PMID- 15142663
TI  - Marinobufagenin may mediate the impact of salty diets on left ventricular
      hypertrophy by disrupting the protective function of coronary microvascular
      endothelium.
AB  - Individuals who eat salty diets and who are "salt-sensitive" tend to have
      increased left ventricular mass, independent of blood pressure; this phenomenon
      awaits an explanation. It is clear that local up-regulation of angiotensin II
      (AngII) production and activity play a key role in the induction of left
      ventricular hypertrophy (LVH). Recent evidence suggests that a healthy coronary
      microvascular endothelium opposes this effect by serving as a paracrine source of
      nitric oxide (NO), a natural antagonist of AngII activity, and that up-regulation
      of this mechanism can account for the protective role of bradykinin with respect
      to LVH. The coronary microvasculature also possesses NAD(P)H oxidase activity
      that can generate superoxide, inimical to the bioactivity of endothelial NO.
      There is now good reason to believe that the triterpenoid marinobufagenin (MBG),
      a selective inhibitor of the alpha-1 isoform of the sodium pump, mediates the
      impact of salty diets on blood pressure;production of MBG by the adrenal cortex
      is boosted when salt-sensitive animals are fed salty diets. It is hypothesized
      that coronary microvascular endothelium expresses the alpha-1 isoform of the
      sodium pump, and that MBG thus can target this endothelium. If that is the case,
      MBG would be expected to decrease membrane potential in these cells;as a
      consequence, superoxide production would be up-regulated, NO synthase activity
      would be down-regulated, and myocardial NO bioactivity would thus be suppressed.
      This would offer a satisfying explanation for the impact of salt and salt
      sensitivity on risk for LVH. If expression of the alpha-1 isoform of the sodium
      pump is a more general property of vascular endothelium, MBG may suppress NO
      bioactivity in other regions of the vascular tree, thereby contributing to other
      adverse effects elicited by salty diets: reduced arterial compliance, medial
      hypertrophy, impaired endothelium-dependent vasodilation, hypertensive/diabetic
      glomerulopathy, increased risk for stroke, and hypertension.

PMID- 15142664
TI  - Consciousness is discontinuous: the perception of continuity requires conscious
      vectors and needs to be balanced with creativity.
AB  - Consciousness is not what it appears to be. While we are awake and alert,
      consciousness appears to be continuous, but actually is broken up into discrete
      intervals. The perception of continuity is critical for cognitive performance,
      linking together an otherwise disparate collection of thoughts. The perception
      requires an understanding of how information changes and evolves between
      conscious intervals. This understanding is analogous to the vectors used by the
      visual system to add motion to otherwise still images. Determining conscious
      vectors, however, is much more complex than determining motion vectors and
      presumably strains cognitive resources. This strain, in turn, limits the ability
      to bring in new information and ideas, creating a tradeoff between continuity and
      creativity. Optimizing this tradeoff may provide significant benefits both for
      common mental tasks and serious neurological conditions.

PMID- 15142665
TI  - Process and accomplishment in academic medicine.
AB  - Medical academic systems are characterized by interplay between accomplishment
      and process. The term accomplishment refers to fulfillment of the system's
      original goals, such as education, research and medical care, whereas the term
      process refers to the culture and structure, which are developed to pursue these
      goals. A mathematical model is developed to simulate the mechanisms that govern
      growth of medical systems over time. Because system performance is easier to
      measure by process than accomplishment, in the long run investments in growth are
      shifted away from accomplishment towards process. In all aging medical systems
      alike, the proportion of process tends to increase at the expense of
      accomplishment.

PMID- 15142666
TI  - Falsifying falsifications: the most critical task of theoreticians in biology.
AB  - Occasionally, experimental biologists obtain results which mystify them so deeply
      that the paradoxical nature of their finding is acknowledged in the paper
      reporting it. This constitutes a more-or-less explicit invitation to those who
      did not perform the experiments - and even those who do not perform experiments
      at all - to propose explanations that eluded the experimenter. A much more
      frequent scenario, however, is that the experimenter asserts confidently that his
      or her data can be explained by a particular model but are at odds with some
      other model. In such circumstances, it is often overlooked that the stated
      falsification of the latter model is error-prone: just as the mystified
      experimenter saw no explanation when in fact there is one, the other experimenter
      may see only one explanation of the data when there are two. The main reason this
      phenomenon is neglected is, of course, the fact that here the theoretician (or
      other experimenter) must take the initiative in critiquing a conclusion that, far
      from troubling the experimenter, may by the time of its publication be a
      cornerstone of his or her research program, so whose refutation may be decidedly
      unwelcome. For precisely this reason, such critiques - especially, perhaps, when
      they come from those who do not do bench work at all and thus have a
      complementary approach to the analysis of data - are fundamental to maximising
      the rate of progress in fields of biology that otherwise risk languishing in ever
      better-studied cul-de-sacs for many years. Computational biology, including
      simulation, plays an especially important role in this, whereas its ability to
      contribute to biology in other ways is often less than its proponents claim. Here
      I discuss some representative examples of falsification-falsification, including
      a previously unpublished analysis of mitochondrial DNA population dynamics in
      cell culture, in the hope of stimulating more theoreticians - and perhaps also
      more experimentalists - to engage in it.

PMID- 15142667
TI  - Consanguinity and cervical cancer: a quizzical response.

PMID- 15142668
TI  - The cause of trigeminal neuralgia.

PMID- 15142669
TI  - A hypothesis of the erythrocyte rigidity in Southeast Asian ovalocytosis.

PMID- 15142670
TI  - Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell
      proliferation and apoptosis during azoxymethane induced colon carcinogenesis in
      rat.
AB  - Preventive intervention of colorectal cancer has become essential as a major
      portion of the population may develop the disease at some points during their
      lives. Diet and nutrition play an important role during this multistep colon
      carcinogenic process. Inhibitory activity of aqueous suspensions of garlic and
      tomato, individually and in combination, were tested on azoxymethane induced
      colon carcinogenesis in Sprague-Dawley rats. The effect was observed on aberrant
      crypt foci (ACF), the preneoplastic lesion. To investigate the mechanism of
      action of the agents used, cell proliferation and the level of apoptosis were
      determined and the expression of cyclooxygenase-2 (COX-2) protein was analyzed in
      the colon. Following treatment, significant inhibition of the level of cell
      proliferation (P<0.01 in garlic; P<0.001 in tomato and P<0.001 in combination
      treatment group with respect to the carcinogen control group), significant
      induction of apoptosis (P<0.01 in garlic treated; P<0.01 in tomato treated and
      P<0.001 in combination treatment group with respect to the carcinogen control
      group) and suppression of COX-2 expression among the treated groups resulted in
      significant reduction in the incidences of ACF (by 45.27% in garlic, 68.24% in
      tomato and 71.62% in combination treatment group). The preventive effect was
      better when the combination of garlic and tomato was administered in comparison
      to the individual treatment groups, suggesting the synergistic action of garlic
      and tomato.

PMID- 15142671
TI  - Hypermethylation of the CpG island of connexin 32, a candiate tumor suppressor
      gene in renal cell carcinomas from hemodialysis patients.
AB  - Long duration of patients on hemodialysis is a large risk for the development of
      renal cell carcinoma (RCC) compared to general patients. However, the
      carcinogenic process is still unclear. On the other hand, we have reported that
      connexin (Cx) 32, a molecule of gap junction, is a new tumor suppressor gene in
      human RCC. In this study, we investigated the clinical significance of
      methylation-dependent silencing of Cx32 gene in the development of the RCC from
      the hemodialysis patients. As the result, we found that the inactivation of Cx32
      through hypermethylation of the promoter regions frequently occurred in non
      cancerous regions as well as cancerous regions of kidneys from hemodialysis
      patients. However, the hypermethylation of Cx32 occurred only in cancerous
      regions but not non-cancerous regions of kidneys from the general patients
      without hemodialysis. Furthermore, the hypermethylation of RASSAF1A, a
      representative tumor suppressor gene in human RCC, occurred in cancerous regions
      but not non-cancerous regions of kidneys from the hemodialysis and general
      patients. These results suggest that Cx32 is a promising tumor suppressor gene
      relating to the early stage of renal carcinogenesis in the hemodialysis patients.

PMID- 15142672
TI  - Critical roles of intracellular thiols and calcium in parthenolide-induced
      apoptosis in human colorectal cancer cells.
AB  - Parthenolide is one of the main components responsible for the anti-inflammatory
      property of Feverfew. Recently, parthenolide has shown to induce apoptosis in
      cancer cells. Here we further studied the mechanism of parthenolide-induced
      apoptosis by focusing on the role of intracellular thiols and calcium in a human
      colorectal cancer cell, COLO 205. Parthenolide rapidly depleted intracellular
      thiols, including both free glutathione (GSH) and protein thiols. Concomitantly,
      there were dose- and time-dependent increases in intracellular reactive oxygen
      species (ROS) and calcium levels. Increased expression of GRP78 protein, a marker
      for endoplasmic reticulum stress was also detected. All these changes preceded
      parthenolide-induced apoptotic cell death. More importantly, pretreatment with N
      acetylcysteine, a precursor of GSH synthesis, protected the cells from
      parthenolide-induced thiol depletion, ROS production, cytosolic calcium increase
      and completely blocked parthenolide-induced apoptosis. On the contrary,
      pretreatment of buthionine sulfoximine, an inhibitor of GSH synthesis sensitized
      the cell to apoptosis. These data clearly demonstrate that the intracellular
      thiols and calcium equilibrium play a critical role in parthenolide-induced
      apoptotic cell death.

PMID- 15142673
TI  - Pro-oxidant environment of the colon compared to the small intestine may
      contribute to greater cancer susceptibility.
AB  - The colon and small intestine have inherent differences (e.g. redox status) that
      may explain the variation in cancer occurrence at these two sites. This study
      examined basal and induced (oxidative challenge) reactive oxygen species (ROS)
      generation, antioxidant enzyme activity and oxidative DNA damage. Basal ROS and
      antioxidant enzyme activities in the colon were greater than in the small
      intestine. During oxidative stress, 8-oxo-deoxyguanosine (8-oxodG) DNA adducts in
      the colon exceeded levels in the small intestine concomitant with increased ROS.
      Thus the colon responds to oxidative stress less effectively than the small
      intestine, possibly contributing to increased cancer incidence at this site.

PMID- 15142674
TI  - Induction of apoptosis in human lung cancer cells by curcumin.
AB  - Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has
      anti-inflammatory, antioxidant and anti-cancer activities. Although the precise
      mode of action of this compound is not yet elucidated, studies have shown that
      chemo-preventive action of curcumin might be due to its ability to induce
      apoptosis and to arrest cell cycle. This study investigated the cellular and
      molecular changes induced by curcumin leading to the induction of apoptosis in
      human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is
      p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM)
      for 12-72 h. Curcumin inhibited the growth of both the cell lines in a
      concentration dependent manner. Growth inhibition of H1299 cell lines was both
      time and concentration dependent. Curcumin induced apoptosis in both the lung
      cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was
      observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes
      remained unchanged up to 60 microM curcumin but showed decrease in expression
      levels at 80-160 microM. The data also suggest a p53 independent induction of
      apoptosis in lung cancer cells.

PMID- 15142675
TI  - VR-3848, a novel peptide derived from Euphobiaceae, induces mitochondria
      dependent apoptosis in human leukemia cells.
AB  - VR-3848, a novel peptide derived from Euphobiaceae, is shown herein to induce
      apoptosis at nanomolar concentrations in the leukemic Jurkat cell line. Apoptosis
      was associated with activation of caspases, release of cytochrome c from
      mitochondria, fragmentation of nuclear DNA, and externalization of
      phosphatidylserine on the cell surface. Overexpression of mitochondria-targeted
      Bcl-2 abrogated VR-3848-induced killing in this model. Primary human interleukin
      (IL)-2-activated T lymphocytes were considerably less sensitive to VR-3848
      induced apoptosis as compared to Jurkat cells. VR-3848 thus holds the promise of
      being a potent and selective anti-cancer agent that deserves further exploration.

PMID- 15142676
TI  - In vivo reversal of doxorubicin resistance by (-)-epigallocatechin gallate in a
      solid human carcinoma xenograft.
AB  - A human carcinoma xenograft model was established with resistant KB-A-1 cell line
      in order to investigate whether (-)-epigallocatechin gallte (EGCG) can reverse
      doxorubicin (DOX) resistance in vivo. EGCG could sensitize the tumors to DOX as
      indicated by a considerable reduction of tumor weights. The combination of DOX
      with EGCG increased the DOX concentration by 51% in the tumors, and increased DOX
      induced apoptosis in the tumors compared with DOX alone. In addition, the
      combination schedules appeared to be well tolerated. We conclude that EGCG could
      chemosensitize resistant tumor cells to DOX in vivo through an increase in the
      accumulation of DOX in the tumors.

PMID- 15142677
TI  - Extracellular cAMP-dependent protein kinase (ECPKA) in melanoma.
AB  - Melanoma is one of the fastest rising malignancies in the United States. When
      detected early, primary melanomas are curable through surgery. However, despite
      significant improvements in diagnosis and surgical, local and systemic therapy,
      mortality rate in metastatic melanoma remains high. Furthermore, genetic
      alterations associated with the development and stepwise progression of melanoma,
      are still unclear. Previous reports show that the catalytic kinase subunit of the
      cAMP-dependent protein kinase is secreted by tumor cells and can be detected in
      the serum of cancer patients. We examine in this report the clinical significance
      of this secreted C subunit kinase termed extracellular protein kinase (ECPKA) in
      melanoma patients. Our results showed the presence of ECPKA activity in the serum
      of melanoma patients and correlate with the appearance and size of the tumor.
      Most importantly, surgical removal of melanoma causes a precipitous decrease in
      ECPKA activity in the sera of patients, suggesting that ECPKA may be a novel
      predictive marker in melanoma.

PMID- 15142678
TI  - Circadian variations of rectal cell proliferation in patients affected by
      advanced colorectal cancer.
AB  - The circadian rhythm of the rectal cell proliferation was studied in five
      patients affected by advanced colon cancer. Biopsies were taken from apparently
      normal mucosa at 10 cm from the anal verge, every 6 h in a 24-h period. Fragments
      were incubated for 1 h in a culture medium containing bromodeoxyuridine (BrdUrd).
      As compared with the mean 24 h values, the percentage of BrdUrd-labelled cells in
      the crypts (Labelling Index, LI) was lower in the specimens collected at 10.00 PM
      (P = 0.02) The LI in such biopsies was also lower than the LI observed at the
      baseline time, 10.00 AM (P = 0.001) The results suggest that the rectal cell
      proliferation in patients with advanced colon cancer fluctuates during the day.
      The study of the rhythmicity of the intestinal cells may be useful to modulate
      the infusion of antiproliferative agents to prevent damage of the normal
      colorectal mucosa.

PMID- 15142679
TI  - Tissue expression and sero-reactivity of tumor-specific antigens in colorectal
      cancer.
AB  - The expression of 14 individual and two groups of tumor antigens was
      characterized for colorectal carcinoma by RT-PCR using 26 colorectal carcinoma
      specimens, eight cell lines, six samples of patients with inflammatory bowl
      diseases, and nine specimens from different locations of an individual patient
      with a metastasized rectal carcinoma. The most frequently detected mRNAs were
      MAGE-A1 (58%), GAGE-3-7 (54%), and cTAGE-5a (31%). At medium frequencies (12-19%)
      we found cTAGE-1, MAGE-A2, se57-1, RAGE-4, and GAGE-1,2,8, while other tumor
      antigens were expressed rarely (<9%). 85% of the samples were positive for at
      least one of the most frequently expressed antigens. Using a secondary SEREX
      approach and sera of eight colorectal cancer patients we found reactive
      antibodies against recombinant cTAGE-1 (2 sera), se57-1 (2), truncated GAGE (1),
      and MAGE-A1 (1). We conclude that certain cancer-germline genes can be detected
      in colorectal cancer and might therefore be promising targets for immunotherapy.

PMID- 15142680
TI  - Inactivation mechanisms and growth suppressive effects of p16INK4a in Asian
      esophageal squamous carcinoma cell lines.
AB  - The inactivation mechanisms and functional role of p16INK4a in three Asian
      esophageal squamous cell carcinoma (ESCC) cell lines were investigated by
      polymerase chain reaction (PCR) amplification, DNA sequencing, methylation
      specific PCR analysis, reverse transcription-PCR, Western blotting, and colony
      formation assays. The p16INK4a was inactivated by promoter hypermethylation in
      all three cell lines, a homozygous deletion of exons 2 and 3, and a frameshift
      deletion on exon 1, leading to transcriptional silencing or the production of
      mutant p16INK4a protein. Two ESCC cell lines transfected with wild type p16INK4a
      show significantly reduced cell growth properties. The results of the present
      studies support the suppressive role of p16INK4a in ESCC development.

PMID- 15142681
TI  - VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell
      carcinoma in relation to p53 status, spontaneous apoptosis and prognosis.
AB  - We have previously reported that p53 mutations, loss of bax expression or
      decreased spontaneous tumor apoptosis were associated with poorer prognoses in
      maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the
      present study, we analyzed tumor angiogenesis monitored by expression of vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor
      microvessel density, in correlation with p53 status, spontaneous apoptosis or
      disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor
      biopsy specimens obtained prior to initiation of treatment were examined for
      expression of VEGF and bFGF and tumor microvessel density using
      immunohistological methods. Average vessel density (AVD) (range: 3-75; median:
      25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by
      the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was
      expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF
      expression showed significantly higher levels of MVD than those without VEGF
      expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently
      in patients with p53 overexpression and/or mutation than in those with normal p53
      status (P=0.048). The MVD inversely correlated with the apoptotic index (AI)
      defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor
      cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant
      metastases after surgery showed significantly higher levels of MVD than patients
      without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of
      radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual
      prognostic factors for maxillary sinus SCC, we selected 57 patients treated
      uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan
      Meier analysis showed that survival was significantly worse in patients with high
      MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest
      that the VEGF expression in association with the p53 overexpression and/or
      mutations may cause increased microvascularity, decreased spontaneous apoptosis
      or metastases, while the bFGF expression may be associated with resistance to
      radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC.
      VEGF and bFGF expression and tumor microvessel density in tumor lesions were
      analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF
      expression dependent of p53 overexpression and/or mutations was associated with
      angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the
      bFGF expression was associated with resistance to radiochemotherapy, resulting in
      poor prognosis.

PMID- 15142682
TI  - Correlation of p53 and bcl-2 expression with vascular endothelial growth factor
      (VEGF), microvessel density (MVD) and clinico-pathological features in colon
      cancer.
AB  - This study was designed to elucidate the possible relationship between tumour
      related genes and angiogenesis in colon cancer. The protein expression of p53,
      bcl-2, Von Willebrand factor and vascular endothelial growth factor (VEGF) were
      analysed by immunohistochemistry in 57 paraffin-embedded colon cancer. The
      results showed that microvessel density (MVD) was lower in VEGF negative tumours
      than in VEGF positive ones (P<0.0001). MVD and VEGF in p53 negative tumours were
      significantly lower than in p53 positive tumours (respectively, P=0.003 and
      P<0.0001). Moreover, positive correlations were recorded between VEGF expression
      and MVD, and bcl-2 expression (respectively, P<0.0001 and P=0.009). Our data
      confirm the central role of VEGF in angiogenesis and suggest direct correlations
      among p53, bcl-2 and VEGF expression in colon cancer.

PMID- 15142683
TI  - Profiling of internalizing tumor-associated antigens on breast and pancreatic
      cancer cells by reversed genomics.
AB  - Human antibodies directed towards functionally associated tumor antigens have
      great potentials as adjuvant treatment in cancer therapy. Here we describe an
      efficient subtractive approach to select single chain Fv (scFv) antibodies,
      specifically binding to unknown rapidly internalizing tumor-associated antigens
      (TAA) on human breast and pancreatic carcinoma cell lines. After re-engineering
      the scFv into intact IgG molecules, these fully human antibodies displayed
      individual binding profiles to TAAs on breast, pancreatic, colorectal and
      prostate carcinomas, while showing no reactivity to lymphomas. The ability of the
      selected antibodies to undergo receptor-mediated internalization was verified by
      confocal microscopy, thus proving our strategy to provide a unique set of human
      antibodies, potentially useful in immunotherapy.

PMID- 15142684
TI  - Cerebral perturbations provoked by prolonged exercise.
AB  - This review addresses cerebral metabolic and neurohumoral alterations during
      prolonged exercise in humans with special focus on associations with fatigue.
      Global energy turnover in the brain is unaltered by the transition from rest to
      moderately intense exercise, apparently because exercise-induced activation of
      some brain regions including cortical motor areas is compensated for by reduced
      activity in other regions of the brain. However, strenuous exercise is associated
      with cerebral metabolic and neurohumoral alterations that may relate to central
      fatigue. Fatigue should be acknowledged as a complex phenomenon influenced by
      both peripheral and central factors. However, failure to drive the motorneurons
      adequately as a consequence of neurophysiological alterations seems to play a
      dominant role under some circumstances. During exercise with hyperthermia
      excessive accumulation of heat in the brain due to impeded heat removal by the
      cerebral circulation may elevate the brain temperature to >40 degrees C and
      impair the ability to sustain maximal motor activation. Also, when prolonged
      exercise results in hypoglycaemia, perceived exertion increases at the same time
      as the cerebral glucose uptake becomes low, and centrally mediated fatigue
      appears to arise as the cerebral energy turnover becomes restricted by the
      availability of substrates for the brain. Changes in serotonergic activity,
      inhibitory feed-back from the exercising muscles, elevated ammonia levels, and
      alterations in regional dopaminergic activity may also contribute to the impaired
      voluntary activation of the motorneurons after prolonged and strenuous exercise.
      Furthermore, central fatigue may involve depletion of cerebral glycogen stores,
      as signified by the observation that following exhaustive exercise the cerebral
      glucose uptake increases out of proportion to that of oxygen. In summary,
      prolonged exercise may induce homeostatic disturbances within the central nervous
      system (CNS) that subsequently attenuates motor activation. Therefore, strenuous
      exercise is a challenge not only to the cardiorespiratory and locomotive systems
      but also to the brain.

PMID- 15142685
TI  - The brain angiotensin system and extracellular matrix molecules in neural
      plasticity, learning, and memory.
AB  - The brain renin-angiotensin system (RAS) has long been known to regulate several
      classic physiologies including blood pressure, sodium and water balance,
      cyclicity of reproductive hormones and sexual behaviors, and pituitary gland
      hormones. These physiologies are thought to be under the control of the
      angiotensin II (AngII)/AT1 receptor subtype system. The AT2 receptor subtype is
      expressed during fetal development and is less abundant in the adult. This
      receptor appears to oppose growth responses facilitated by the AT1 receptor, as
      well as growth factor receptors. Recent evidence points to an important
      contribution by the brain RAS to non-classic physiologies mediated by the newly
      discovered angiotensin IV (AngIV)/AT4 receptor subtype system. These physiologies
      include the regulation of blood flow, modulation of exploratory behavior, and a
      facilitory role in learning and memory acquisition. This system appears to
      interact with brain matrix metalloproteinases in order to modify extracellular
      matrix molecules thus permitting the synaptic remodeling critical to the neural
      plasticity presumed to underlie memory consolidation, reconsolidation, and
      retrieval. There is support for an inhibitory influence by AngII activation of
      the AT1 subtype, and a facilitory role by AngIV activation of the AT4 subtype, on
      neuronal firing rate, long-term potentiation, associative and spatial learning.
      The discovery of the AT4 receptor subtype, and its facilitory influence upon
      learning and memory, suggest an important role for the brain RAS in normal
      cognitive processing and perhaps in the treatment of dysfunctional memory disease
      states.

PMID- 15142686
TI  - Stopping warfarin therapy is unnecessary for hand surgery.
AB  - Interruption of appropriate therapeutic warfarin therapy imposes a risk of
      morbidity and mortality on the patient. Strategies to reduce the risks of
      interruption impose relatively large costs in terms of prolonged hospital stay,
      medication and coagulation monitoring. We report a series of 47 consecutive
      surgical episodes on the hands of 39 patients without interruption of therapeutic
      warfarin anticoagulation and with an INR of between 1.3 and 2.9. There was no
      difficulty with intraoperative haemostasis. Two patients had minor bleeding
      related complications with no long-term sequelae. The authors conclude that
      interruption to warfarin therapy is unnecessary if the INR is less than 3.0 and
      therefore inappropriate for therapeutically anticoagulated patients undergoing
      hand surgery.

PMID- 15142687
TI  - Elective hand surgery in patients taking warfarin.
AB  - We reviewed 22 patients who had undergone either carpal tunnel decompression or
      release of Dupuytren's contractures while anticoagulated with warfarin. All
      patients continued with their usual anticoagulant regime over the period of
      operation, provided that the international normalized ratio (INR) was 3 or less.
      There was no abnormal intraoperative or postoperative bleeding in any patient.
      Journal of Hand Surgery (British and European volume, 2004).

PMID- 15142688
TI  - Arthroscopic findings in wrists with severe post-traumatic pain despite normal
      standard radiographs.
AB  - This study assessed the role of diagnostic arthroscopy following a wrist injury
      in patients with normal standard radiographs, an unclear clinical diagnosis and
      persistent severe pain at 4 to 12 weeks. Forty-three patients were included after
      conservative management had failed to improve their wrist pain so that a
      stability test could be performed satisfactorily and underwent arthroscopy within
      12 weeks. Arthroscopy revealed recent pathology in 41 wrists, of which 17 had
      significant ligament lesions that might have benefited from acute repair. We
      conclude that patients with marked persistent post-traumatic symptoms despite
      conservative management are likely to have sustained ligament injuries despite
      normal radiographs. We therefore recommend that under these circumstances an
      arthroscopy is carried out within 4 weeks if the patient and surgeon wish to
      acutely repair significant ligament injuries.

PMID- 15142689
TI  - A prospective study of the treatment of fractures of the little finger metacarpal
      shaft with a short hand cast.
AB  - This prospective study describes the use of a short hand cast, which leaves the
      finger metacarpophalangeal and wrist joint free, for angularly displaced little
      finger metacarpal shaft fractures which require reduction. Twenty-seven patients
      with a mean age of 25 (range, 16-39) years with little finger or combined ring
      and little finger displaced metacarpal shaft fractures were prospectively
      recruited. All were treated by closed fracture reduction and immobilization in
      the cast. Patients were followed up at 1 week, 4 weeks, and between 6 and 12
      months. At each of these follow-up visits posteroanterior and lateral radiographs
      of the metacarpals were performed to assess angulation of the fracture. The mean
      initial angulation of the 17 little finger metacarpal fractures with complete
      follow up was 40 degrees (range, 20-60 degrees ). Their mean final angulation at
      6 to 12 months was 8 degrees. The fracture reduction was lost in three patients
      in whom the final angular deformities were 15 degrees (one patient) and 20
      degrees (two patients). Journal of Hand Surgery (British and European volume,
      2004)

PMID- 15142690
TI  - Plating of metacarpal fractures: unicortical or bicortical screws?
AB  - Mid-shaft transverse osteotomies were performed in 18 cadaveric metacarpals and
      randomly divided into two groups. Using dorsally applied plates for repair, one
      group was secured using 6mm unicortical screws, while bicortical screws were used
      in the second group. The metacarpals were tested to failure with a four-point
      bending protocol using a servo-hydraulic testing machine and a 1kN load cell. The
      mean load to failure was 596N (SD=142) for the unicortical and 541N (SD=171) for
      the bicortical group. The stiffness was 333N/mm (SD=116) for the unicortical and
      458N/mm (SD=158) for the bicortical group. Both load to failure and stiffness
      were not statistically significant between the two groups. Failure occurred by
      fracture at the screw-bone interface in all specimens: no screw pull-out was
      observed. No biomechanical advantage was found when using bicortical screws in
      metacarpal fracture plating.

PMID- 15142691
TI  - The multiple monoblock toe-to-hand transfer in digital reconstruction. a report
      of ten cases.
AB  - Ten hands with multiple traumatic finger amputations or congenital agenesis
      underwent reconstruction by monoblock transfer of multiple toes. Eight patients
      underwent monoblock transfer of the great and second toes, one patient received
      the great toe and the metatarsophalangeal joint from the second toe with the same
      vascular pedicle, and another patient the great, second and third toes as a
      block. Only part of the great toe was ever taken, while the second toe was
      totally or partially taken. The surgical technique and the outcome are detailed
      in this work, with a mean postoperative follow-up of 6 years.

PMID- 15142692
TI  - Thrombosis and altered expression of intercellular adhesion molecule-1 (ICAM-1)
      after avulsion injury in rat vessels.
AB  - This study was undertaken to characterize the relative degrees of arterial and
      venous trauma after graded avulsion injuries. Rat femoral arteries and veins were
      subjected to reproducible avulsion injuries using forces of between 60 and 220g.
      Thrombotic occlusion occurred at lower avulsion forces in veins than in arteries.
      Histologic and scanning electron microscopic analysis indicated increased
      endothelial disruption and exposed elastic lamina with increasing avulsion force
      in both vessels, but more prominently in arteries. Intercellular adhesion
      molecule-1 (ICAM-1) mRNA expression was evident at 3 and 6 hours after avulsion
      injury in veins, but only with higher avulsion-force injuries in arteries. ICAM-1
      mRNA expression was not found in either vessel before or after this 3 to 6 hour
      post-injury interval. These results indicate that the amount of avulsion force to
      which traumatized extremity vessels are subjected has a direct effect on the
      degree of intimal injury and subsequent thrombosis.

PMID- 15142693
TI  - Surgery for Dupuytren's disease in Japanese patients and a new preoperative
      classification.
AB  - The surgical outcome of Dupuytren's disease was evaluated in 73 hands of 57
      patients in a Japanese population. Subtotal fasciectomy was performed in all
      cases. Surgical results were evaluated using the percentage improvement of
      extension in each finger joint. Statistical analyses were performed on the risk
      factors associated with recurrence and extension. The surgical outcome depended
      on the degree of contracture of the proximal interphalangeal joint. Recurrence of
      disease occurred in eight patients (14%) and extension occurred in nine (16%).
      Recurrence and extension frequently occurred in those who had ectopic lesions or
      involvement of the radial side of the hand. The present results suggested that
      the Dupuytren's diathesis had an influence on recurrence and extension. We
      proposed a new classification of Dupuytren's disease that might help to predict
      the surgical outcome and facilitate surgical planning.

PMID- 15142694
TI  - Severe contracture of the proximal interphalangeal joint in Dupuytren's disease:
      does capsuloligamentous release improve outcome?
AB  - This prospective study assessed whether patients with severe proximal
      interphalangeal joint contracture (#10878;60 degrees ) due to Dupuytren's disease
      which persisted after fasciectomy alone benefited from an additional
      capsuloligamentous release. Forty-three patients with 43 severely contracted
      proximal interphalangeal joints underwent operative correction followed by a
      standardized postoperative rehabilitation programme. All were followed for 6
      months. In 11 patients correction of the proximal interphalangeal joint to 20
      degrees could not be achieved by fasciectomy alone, and an additional
      capsuloligamentous release was performed which effectively corrected all their
      residual flexion contractures. There were no statistically significant
      differences between the capsulotomy and the non-capsulotomy group with respect to
      the residual proximal interphalangeal joint contracture at the end of surgery, or
      at their last follow-up examination.

PMID- 15142695
TI  - Morphological measurements of the proximal interphalangeal joint.
AB  - The morphology of the proximal interphalangeal joint was determined using a
      photographic technique. The head of the proximal phalanx, viewed end on, has a
      complex trapezoid appearance characteristic for each named digit. The asymmetric
      condyles diverge from one another and are separated by an intercondylar groove
      that increases in depth from the dorsal to the palmar surface. Saggital sections
      of the head of the proximal phalanx are not circular, but, sections taken in the
      plane of maximum dimensions of the condyle are circular with a radius of
      curvature of approximately one half of the height of the condyles. The articular
      surface of the base of the middle phalanx is not circular in outline in either
      the saggital or coronal plane. In coronal sections the articular surface is
      biconcave convex with a prominent median ridge separating the two adjacent
      concave articular surfaces. The implications of this varied morphology on implant
      design are discussed.

PMID- 15142696
TI  - Immediate repair and early mobilization of the extensor pollicis longus tendon in
      zones 1 to 4.
AB  - We present the results of repair and early mobilization of 100 extensor pollicis
      longus (EPL) tendon injuries in zones 1 to 4 in 100 patients using a dynamic
      outrigger splint which controlled metacarpophalangeal joint movements but allowed
      free movement of the interphalangeal joint. Eighty-two were complete divisions of
      the tendon and 18 were 80% to 99% tendon divisions. Analysis of measurements
      obtained routinely at 8 weeks showed 81% excellent and good results using the TAM
      system. There were 90% excellent and good results in the 72 patients, who were
      followed-up and received therapy for 12 weeks. Except on the rare occasion when
      the repair rupture, loss of thumb extension was not a common functional problem,
      but scar tethering of the repaired tendon could result in loss of thumb flexion.
      While loss of metacarpophalangeal joint flexion appeared to have little
      functional importance, loss of interphalangeal joint flexion and slowing of the
      movements of this joint could cause functional problems. When interphalangeal
      joint hyperextension is present before the injury, it is frequently lost but this
      generally goes unnoticed by the patients. The problems of analysing the EPL
      injury using the methods of assessment available are discussed.

PMID- 15142697
TI  - Mechanical evaluation of the Pronator Teres rerouting tendon transfer.
AB  - We simulated pronator teres rerouting using a three-dimensional biomechanical
      model of the arm. Simulations comprised the evaluation of changes in muscle
      length and the moment arm of pronator teres with changes in forearm axial
      rotation and elbow flexion. The rerouting of Pronator Teres was simulated by
      defining a path for it through the interosseous membrane with re-attachment to
      its original insertion. However the effect of moving the insertion to new
      positions, 2 cm below and above, the original position was also assessed. The
      effect on total internal rotation and external rotation capacity was determined
      by calculating the potential moments for pronator teres, supinator, pronator
      quadratus, biceps brachii and brachioradialis. Pronator teres was found to be a
      weak internal rotator in extreme pronation, but a strong internal rotator in
      neutral rotation and in supination. After rerouting pronator teres was only a
      strong external rotator in full pronation and not at other forearm positions,
      where the effect of rerouting was comparable to a release procedure.

PMID- 15142698
TI  - Brachioradialis re-routing for the restoration of active supination and
      correction of forearm pronation deformity in cerebral palsy.
AB  - A brachioradialis muscle rerouting procedure was used to restore active
      supination in five children with cerebral palsy and a pronation deformity.
      Following release and lengthening of the pronator quadratus and pronator teres
      muscles, respectively, the brachioradialis tendon was divided as a Z plasty and
      the distal part of the tendon was passed through the interosseous space in a
      dorsal to palmar direction, and then sutured to its proximal end. The procedure
      resulted in a gain of 81 degrees of active supination.

PMID- 15142699
TI  - Carpal tunnel decompression. Is lengthening of the flexor retinaculum better than
      simple division?
AB  - This prospective randomized double-blind control trial compared lengthening and
      simple division of the flexor retinaculum in carpal tunnel decompression. Twenty
      six patients with bilateral carpal tunnel syndrome were randomly allocated to
      have the flexor retinaculum divided on one side and lengthened on the other. All
      52 hands were reviewed at regular intervals up to 25 weeks. The patients,
      therapists and the final reviewer were unaware of treatment allocation. The
      Levine symptom and function scores were used to assess the severity of the carpal
      tunnel syndrome and showed that the two treatments were comparable for relief of
      carpal tunnel symptoms. The two treatments were also similar for function
      measured with the Jebsen-Taylor test. There is no identifiable benefit in
      lengthening the flexor retinaculum when decompressing the carpal tunnel. Moderate
      or severe pillar and scar pain is common, occurring in 13 of 52 hands after
      surgery, but only in four by the 12th week and two by the 25th week.

PMID- 15142701
TI  - Aetiology of Kienbock's disease.

PMID- 15142700
TI  - Relationship of carpal canal contents volume to carpal canal pressure in carpal
      tunnel syndrome patients.
AB  - Forty patients long-term haemodialysis with a second recurrence of carpal tunnel
      syndrome and concomitant loss of flexor tendon function due to flexor adhesions
      were treated by excision of the flexor digitorum superficialis tendons. During
      the procedure the carpal canal pressure was measured using a continuous infusion
      technique. The preoperative mean carpal canal pressure was 81 (SD, 53)mmHg. After
      removal of all the flexor digitorum superficialis tendons, the carpal canal
      pressure decreased to 10 (SD, 8)mmHg. The clinical symptoms of carpal tunnel
      syndrome were relieved and hand strength and finger motion were improved in all
      patients.

PMID- 15142702
TI  - Juvenile lunatomalacia is this Kienbock's disease?
AB  - An 8-year-old boy with stage III Kienbock's disease was treated by immobilization
      of the wrist. He made a complete clinical recovery and serial X-rays and MRI
      scans demonstrated complete revascularization of the lunate which regained near
      normal architecture.

PMID- 15142703
TI  - Darier's disease, an unusual problem and solution.
AB  - A 46-year-old woman with Darier's disease was referred suffering from severe nail
      involvement. The patient suffered constant nail infections and an intolerable
      cycle of progressively more deformity. On examination the patient's nails and
      nail folds were badly deformed. Initially, as a test, a procedure was undertaken
      on the thumb alone. The operation was performed under tourniquet control with a
      digital nerve block. An eponychial flap was raised and nail complex excised. A
      full thickness skin graft was obtained from the groin. This was sutured into
      place with the proximal border of graft tucked under the eponychial fold. The
      results were excellent both surgically and cosmetically. Subsequently, procedures
      were performed on the remaining nine digits. Darier's disease is extremely
      variable in its degree of nail involvement. This case highlights a surgical
      intervention that may help people with intractable associated nail disease.

PMID- 15142704
TI  - The history of hand surgery in Hungary.

PMID- 15142705
TI  - Biomechanical analysis of a modification of Tang method of tendon repair.

PMID- 15142707
TI  - A new clinical severity scoring system for reflex sympathetic dystrophy of the
      upper limb.

PMID- 15142709
TI  - Stenotrophomonas maltophilia: the significance and role as a nosocomial pathogen.
AB  - Stenotrophomonas maltophilia is a significant pathogen that primarily affects
      patients with co-morbid illnesses, usually malignancies, who have been
      hospitalized for prolonged periods and received broad-spectrum antibiotic
      therapy. The organism has been associated with an expanding spectrum of clinical
      manifestations associated with high case to fatality ratios. Therapy of these
      infections presents a significant challenge both for the clinician and the
      microbiologists because of its high-level antibiotic resistance to most of the
      currently used agents and methodological difficulties in susceptibility testing
      with this organism.

PMID- 15142710
TI  - Candidosis in the intensive care unit: a 20-year survey.
AB  - Deep-seated candidosis is a major problem in critically ill patients.
      Colonization with candida has been identified as an important independent risk
      factor for the development of candidaemia. Since the 1980s routine surveillance
      cultures have been performed on patients admitted for six or more days to the 'E.
      Vecla' intensive care unit (ICU) of the IRCCS Ospedale Maggiore di Milano.
      Colonization was observed on admission to the ICU in 59 of 117 (50%) patients in
      2000 and 10 others developed colonization during their stay on the unit. A
      similar colonization rate was found in a survey performed 16 years earlier. The
      incidence of non-albicans Candida species, however, increased in 2000. In
      particular, 24 patients were culture positive for Candida glabrata at some point
      during their hospital stay, whereas this species was isolated from only one
      patient in 1983-1984. Antifungal susceptibility testing performed by Sensititre
      Yeast One revealed no resistance among 19 C. albicans strains tested. In
      contrast, fluconazole resistance was observed in two of 39 (5%) C. glabrata
      isolates from 23 patients. In the period 1983-2002, 28 candida bloodstream
      infections were identified and 12 were considered to be ICU-acquired (2.6/1000
      hospitalized patients; 0.33/1000 patient days). The low rate of ICU-acquired
      candidaemia despite the inclusion of severely compromised patients in this study
      confirms the usefulness of routine mycological surveillance in preventing deep
      seated candidosis.

PMID- 15142711
TI  - Surgical-site infections within 60 days of coronary artery by-pass graft surgery.
AB  - Surgical wound infections (SWIs) after coronary artery by-pass graft (CABG)
      within 30 and 60 days of operation were registered. Already known risk factors
      and possible risk factors for wound infection were studied. SWIs of sternal
      and/or leg wounds have been reported to occur in 2-20% of patients after CABG.
      Deep sternal infection, mediastinitis, occurs after 0.5-5% of CABG procedures.
      The duration and methods of follow-up, as well as definitions of SWI, vary in
      different studies. Previously known and possible new risk factors were registered
      for 374 patients. Patients were contacted by telephone 30 and 60 days after
      surgery and interviewed in accordance with a questionnaire about symptoms and
      signs of wound infections. Our definition of SWI was based on the Centers for
      Disease Control and Prevention (CDC) definition. SWIs were diagnosed in 114 of
      374 (30.5%) of the patients. In total SWI were diagnosed in 120 surgical-site
      incisions. Almost all SWIs of the sternum (93.3%) were diagnosed within 30 days
      of surgery. Most of the SWIs of the leg (73%) were diagnosed within 30 days of
      surgery and 27% were diagnosed within 31 to 60 days of surgery. Being female was
      the most important risk factor for SWI of the leg. Low preoperative haemoglobin
      concentrations were the most important risk factor for superficial SWI on the
      sternum. Patients with mediastinitis had higher BMI and had more often received
      erythrocyte transfusions on postoperative day two or later than those without
      infections.

PMID- 15142712
TI  - Surgical-site infections after orthopaedic surgery: statewide surveillance using
      linked administrative databases.
AB  - Prospective surveillance programmes to monitor the incidence of surgical-site
      infection (SSI) in patients who have had orthopaedic implant surgery can be
      difficult to implement due to limited human and technical resources. In addition,
      prolonged patient follow-up, up to one year, may be required. Traditional methods
      of surveillance can be enhanced by using administrative databases to assist in
      case finding and facilitate overall surveillance activities. The aim of this
      study was to identify the incidence of SSI in patients who had undergone total
      hip replacement (THR) or total knee replacement (TKR) surgery in all Western
      Australian (WA) hospitals during 1999 using the Western Australian Data Linkage
      System. The WA Data Linkage System links several population-based administrative
      health datasets within the state, including the Hospital Morbidity Data System
      (HMDS), containing International Classification of Disease-coded discharge
      information, and mortality records. A total of 1476 THR and 1875 TKR procedures
      was identified from 21 WA hospitals during 1999. The incidence of SSI after these
      procedures was 5% (95% CI 4.3-5.7) [THR (4.86%, 95% CI 3.77-5.95) and TKR (5.15%,
      95% CI 4.15-6.15)]. The incidence was 33.72 infections per 1000 person-years.
      Patients aged over 80 years experienced a significantly higher rate of infection
      after THR compared with patients aged 80 or less (z-test, z = 2.56, P = 0.015),
      but not for TKR. No patients with an SSI died during follow-up. The WA Data
      Linkage System provided a unique opportunity to review the incidence of SSIs in
      patients undergoing THR or TKR surgery in WA hospitals.

PMID- 15142714
TI  - Investigation of a pyoderma outbreak caused by methicillin-susceptible
      Staphylococcus aureus in a nursery for newborns.
AB  - An outbreak of pyoderma caused by methicillin-susceptible Staphylococcus aureus
      occurred in a nursery for newborns over 26 days. During this period, six neonates
      were involved. The mother of the first case had trunk pyoderma before delivery,
      which was regarded as the source of the outbreak. Contamination of the
      environment and equipment were implicated as the reservoirs of further pathogen
      spread, as supported by pulsed-field gel electrophoresis (PFGE) results, which
      showed that some screening isolates were indistinguishable from the epidemic
      strain. Termination of the outbreak was achieved by the reinforcement of
      infection control practices and disinfection of environmental surfaces.

PMID- 15142713
TI  - Tackling contamination of the hospital environment by methicillin-resistant
      Staphylococcus aureus (MRSA): a comparison between conventional terminal cleaning
      and hydrogen peroxide vapour decontamination.
AB  - The hospital environment can sometimes harbour methicillin-resistant
      Staphylococcus aureus (MRSA) but is not generally regarded as a major source of
      MRSA infection. We conducted a prospective study in surgical wards of a London
      teaching hospital affected by MRSA, and compared the effectiveness of standard
      cleaning with a new method of hydrogen peroxide vapour decontamination. MRSA
      contamination, measured by surface swabbing was compared before and after
      terminal cleaning that complied with UK national standards, or hydrogen peroxide
      vapour decontamination. All isolation rooms, ward bays and bathrooms tested were
      contaminated with MRSA and several antibiogram types were identified. MRSA was
      common in sites that might transfer organisms to the hands of staff and was
      isolated from areas and bed frames used by non-MRSA patients. Seventy-four
      percent of 359 swabs taken before cleaning yielded MRSA, 70% by direct plating.
      After cleaning, all areas remained contaminated, with 66% of 124 swabs yielding
      MRSA, 74% by direct plating. In contrast, after exposing six rooms to hydrogen
      peroxide vapour, only one of 85 (1.2%) swabs yielded MRSA, by enrichment culture
      only. The hospital environment can become extensively contaminated with MRSA that
      is not eliminated by standard cleaning methods. In contrast, hydrogen peroxide
      vapour decontamination is a highly effective method of eradicating MRSA from
      rooms, furniture and equipment. Further work is needed to determine the
      importance of environmental contamination with MRSA and the effect on hospital
      infection rates of effective decontamination.

PMID- 15142715
TI  - The procedures of hygiene to control hospital-acquired diarrhoea in paediatric
      wards: a multicentre audit.
AB  - An audit was carried out in paediatric wards to study the compliance of
      healthcare workers (HCWs) to the procedures recommended for the control of
      hospital-acquired diarrhoea. Thirty-two paediatric wards in the southeast of
      France participated on a voluntary basis in this prospective observational study
      after completing a self-administered questionnaire recording measures of hygiene.
      All the observations were made by the same investigator and focused on preventive
      procedures: use of single room, handwashing, hand disinfection, overclothing,
      single-use gloves and masks. Two hundred and seventy patient-HCW contacts were
      observed, including mainly diapering, temperature measurement, collection of
      blood sample and catheter care. The isolation of patients in a single room and
      use of gowns by HCWs were significantly associated with diarrhoea. Whereas
      handwashing before care was performed by HCWs in more than 95% of all the
      procedures, the compliance in the use of disposable gloves by HCWs was only of
      39.4% for technical procedures (including those with potential exposure to blood)
      and 20.3% for diapering or temperature measurement. A substantial agreement
      between reported and observed measures of hygiene was observed for handwashing
      before contact and hand disinfection with antimicrobial soap before contact. In
      contrast, this agreement was moderate for use of single room, handwashing after
      contact, overclothing and wearing disposable gloves after a diaper change.
      Despite the excellent compliance of HCWs to handwashing, clearer recommendations
      for the indication and use of disinfectants and disposable gloves are urgently
      needed.

PMID- 15142716
TI  - Employment of 16 S rDNA gene sequencing techniques to identify culturable
      environmental eubacteria in a tertiary referral hospital.
AB  - Universal or 'broad-range' eubacterial polymerase chain reaction (PCR) was
      performed on 53 isolates from environmental water-associated sites in a
      haematology unit (N = 22) and the outer surfaces of cleaning lotion containers
      sited throughout a tertiary referral hospital (N = 31) 16 S rDNA PCR was
      performed using two sets of universal primers, including the novel reverse
      primer, XB4, to generate a composite amplicon of 1068 bp, which was sequenced to
      obtain each isolate's identity. Sequence analysis was able to identify 51
      isolates. Most (75% from the haematology unit and 81% from cleaner containers)
      were Gram-positive. Nine different genera were identified from the haematology
      unit and 13 from the cleaning lotion containers. This study provides the first
      reports of Terrabacter spp. and Brachybacterium paraconglomeratum isolated from a
      hospital environment. As unusual and difficult-to-identify environmental
      organisms are unlikely to be clinically significant, and molecular identification
      is costly and labour-intensive, we recommend that molecular methods are only used
      as an adjunct to first-line phenotypic identification schemes where a definitive
      identification is required. Where molecular identification methods are justified,
      partial 16 S rDNA PCR and sequencing employing the novel universal primer XB4, is
      a valuable and reliable technique.

PMID- 15142717
TI  - Sensitivity of human adenoviruses to different groups of chemical biocides.
AB  - As it is no longer readily permissible to propagate polioviruses, adenoviruses
      will probably become more frequently used for virucidal testing of broad-spectrum
      disinfectants. We tested prototype strains of different adenovirus serotypes
      belonging to the subgenera C and D for sensitivity to liposomal povidone-iodine
      (PVP-I), peracetic acid (PAA) and formaldehyde. Virucidal assays were performed
      as suspension tests in accordance with the German guidelines for testing the
      effectiveness of chemical disinfectants against viruses. The sensitivity of the
      adenovirus serotypes to test disinfectants varied greatly. Prototype strains of
      adenovirus 5 and 44 statistically selected as 'little sensitive' to PVP-I, PAA
      and formaldehyde were found to be the most resistant. These might be suitable as
      model viruses for testing the broad-spectrum virucidal activity of disinfectants
      and might even replace the resistant poliovirus type 1. The main reason for the
      different chemical sensitivity of adenovirus serotypes may be the composition of
      the viral capsid proteins. Alternatively a different chemical inactivation of the
      viral genome could be involved.

PMID- 15142718
TI  - Inactivation of human adenovirus genome by different groups of disinfectants.
AB  - Human adenoviruses are model viruses for testing the virucidal efficacy of
      disinfectants. However, a recent study has shown that the chemical sensitivity of
      adenovirus serotypes varies significantly, possibly due to the composition of the
      viral capsid and/or the resistance of nucleic acids. We have investigated the
      effect of molecular changes in the viral genome of the human adenovirus subgenera
      C and D. A common oligonucleotide fragment within the hexon gene was amplified by
      polymerase chain reaction (PCR) after exposure to liposomal povidone-iodine (PVP
      I), peracetic acid (PAA), and formaldehyde. The findings were compared with
      infectivity in cell cultures. PVP-I (0.125%) destroyed the infectivity of most
      serotypes within 60 min. However, PCR revealed no destruction of the adenoviral
      genome in most serotypes, even after exposure to higher PVP-I concentrations. PAA
      (0.5%) failed to inactivate the hexon gene of adenovirus types 22 and 44.
      Furthermore, the hexon gene of adenovirus type 22 was not altered by 0.7%
      formaldehyde. In conclusion, the genomes of human adenoviruses show considerably
      more chemical resistance than the complete viral particle. The molecular
      resistance of individual serotypes also varies. However, there was no clear
      correlation between the differences in the effect of disinfectants on infectivity
      of the complete viral particle and destruction of the viral genome.

PMID- 15142719
TI  - Rapid inactivation of vaccinia virus in suspension and dried on surfaces.
AB  - A bioterrorist attack with smallpox virus would be disastrous with a 30% disease
      fatality rate. Such an outbreak would require biomedical laboratories for
      diagnosis and analyses and extensive use of clinical care facilities for patient
      quarantine. Safe decontamination procedures will have to be in place in order to
      limit the spread of the disease. In order to fulfil this need, Sanytex, a new non
      corrosive commercial solution containing quaternary ammonium, aldehydes, alcohol
      and detergent, was tested with a view to using it in decontamination procedures.
      Vaccinia virus was used in this investigation as a model for smallpox virus. We
      determined exposure time and the concentration of Sanytex required to inactivate
      the virus in suspension and dried on surfaces in the presence of protein (up to
      70 mg/mL). After 3 min incubation, Sanytex at a concentration of 3% led to a
      complete inactivation (virus titre reduction >10(4)-fold of vaccinia virus in
      suspension containing protein up to 30 mg/mL. A virus suspension containing 70 mg
      protein/mL, simulating biological fluids, was decontaminated with 10% Sanytex
      after 3 min. After 10 min, Sanytex at a concentration of 30%, applied on to a
      dried vaccinia virus contaminated surface in the presence of protein (10 mg/mL
      before desiccation), led to complete decontamination of the surface. Thirty
      minutes exposure with 30% Sanytex was necessary for a virus titre reduction of
      >10(4)-fold on a surface contaminated with a dried suspension of vaccinia virus
      in the presence of protein at 70 mg/mL. Sanytex is not corrosive, not toxic to
      environment and stable for up to three months even diluted. Its virucidal effect
      was preserved when used under pressure in a fire-hose nozzle. These results
      support the use of Sanytex for decontamination of biological fluids and surfaces
      contaminated by the smallpox virus.

PMID- 15142720
TI  - Activity of an alkaline 'cleaner' in the inactivation of the scrapie agent.
AB  - The capacity of a routinely available alkaline cleaner for medical devices to
      inactivate the causative agent of a transmissible spongiform encephalopathy (TSE)
      was tested. The co-incubation of brain homogenates, prepared from terminally ill
      scrapie-infected hamsters, with the cleaner led to the denaturation of misfolded
      protein as the proteinase K-resistant prion protein was no longer detectable
      after such treatment. In addition, intra-cerebral inoculation of hamsters with
      the alkaline cleaner-treated and subsequently neutralized samples reduced the
      level of infectivity of the material below the limit of detection. This report
      shows the possibility that a routinely available alkaline cleaner could reduce
      the infectivity of TSE agents and so minimize the risk of iatrogenic transmission
      of TSEs by asymptomatic carriers. This study is intended to encourage further
      investigations in this field.

PMID- 15142721
TI  - Monitoring Aspergillus species by quantitative PCR during construction of a multi
      storey hospital building.
AB  - During the enlargement of an existing hospital, quantitative polymerase chain
      reaction (PCR) was used to monitor Aspergillus spp. populations within the
      construction site. The rapid availability of results meant that the construction
      schedule was largely uninterrupted, while assuring that the new construction was
      free from contamination by the targeted Aspergillus spp.

PMID- 15142722
TI  - Outbreak of Pseudomonas putida bacteraemia in a neonatal intensive care unit.
AB  - During the period of 9-27 March 2001, Pseudomonas putida strains were recovered
      from 10 neonates hospitalized in the neonatal intensive care unit of Farhat
      Hached Hospital, Sousse (Tunisia). Seven neonates developed bacteraemia, and
      three had an umbilical catheter-related infection (without bacteraemia). A total
      of 18 isolates were cultured from blood (N = 11) and catheters (N = 7). These
      isolates were identified as P. putida by routine biochemical methods (API 20 NE,
      bioMerieux, Lyon, France). Restriction endonuclease DNA profiles were determined
      by pulsed-field gel electrophoresis using two endonucleases XbaI and SpeI. They
      yielded the same patterns showing that the outbreak was caused by a single clone
      of P. putida. Although the antiseptic solutions used to clean the umbilicus were
      implicated circumstantially as probable sources, they were not sampled and so
      this could not be confirmed.

PMID- 15142723
TI  - One hour versus 24 h sampling intervals for the screening of patients with
      methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 15142724
TI  - Whom did you meet on your travels?

PMID- 15142725
TI  - In vitro hydrolysis of poly(L-lactide) crystalline residues as extended-chain
      crystallites. Part I: long-term hydrolysis in phosphate-buffered solution at 37
      degrees C.
AB  - Poly(L-lactide) (PLLA) crystalline residues or extended-chain crystallites
      containing a trace amount of chains in an amorphous state were prepared by
      hydrolysis of crystallized PLLA films in a phosphate-buffered solution (PBS) at
      97 degrees C for 40h. Their in vitro hydrolysis behavior and mechanism were
      investigated in PBS at 37 degrees C for the periods of time up to 512 days using
      gel permeation chromatography (GPC), gravimetry, differential scanning
      calorimetry, and wide angle X-ray diffractometry. The GPC results showed that the
      hydrolysis of the crystalline residues proceeded from their surface composed of
      very short chains with a free end along the chain direction but the hydrolysis
      from their lateral surface could not be traced. The average hydrolysis rates of
      PLLA crystalline residues estimated from the changes of number-average and peak
      top molecular weights (M(n) and M(t), respectively) were 5.31 and 5.01gmol(
      1)day(-1), respectively. Such low hydrolysis rates mean that the PLLA crystalline
      residues can remain for a long period such as ca. 2x10(3) days (ca. 5.5 years) in
      the human body even after PLLA loses its functions as biomaterials. The increased
      melting temperature (T(m)) and crystallinity (X(c)) (in 320 days), and the
      decreased half-widths of X-ray diffraction peaks (in 320 days) during hydrolysis
      were attributed to the decreased lattice disorder of the PLLA crystalline
      residues. On the other hand, the decreased X(c) for the hydrolysis period
      exceeding 320 days was ascribed to the decreased thickness or M(n) of the
      crystalline residues, which increased the effect of the surface having a large
      surface energy.

PMID- 15142726
TI  - Cytological evaluation of the tissue-implant reaction associated with
      subcutaneous implantation of polymers coated with titaniumcarboxonitride in vivo.
AB  - The aim of the present study was to evaluate the influence of titanium-coated
      polymers on the inflammatory response and remodeling of connective tissue during
      wound-healing processes. Discs of polyethyleneterephthalate (PET) and silicone as
      well as high-weight meshes of polypropylene (PP) were coated with a
      titaniumcarboxonitride (Ti(C,N,O)) layer by a plasma-assisted chemical vapor
      deposition process (PACVD) and implanted subcutaneously in the dorsal lumbar
      region of Wistar rats. Light microscopic and histological evaluation of capsule
      thickness, capsule quality, implant-tissue interface and collagen composition was
      performed 7, 14, 21 and 28 days post-operatively. All implants were surrounded by
      a fibrous capsule with decreasing thickness after 2-4 weeks post-implantation.
      Titaniumcarboxonitride-coated polymers showed no significant differences in
      capsule thickness and inflammatory cellular response. An increased collagen type
      III/I ratio, especially for titaniumcarboxonitride-coated materials, was found in
      week one after implantation remaining elevated up to week 4. This might be
      associated with disordered collagen metabolism and immature scar reaction. In
      contrast to previous in vitro experiments, Ti-coating of polymers did not improve
      biocompatibility after subcutaneous implantation in rats. Material reduction to
      low-weight meshes and enlargement of pore size may demonstrate a benefit of Ti
      coated meshes with an increased biocompatibility.

PMID- 15142727
TI  - Effect of composite resin biodegradation products on oral streptococcal growth.
AB  - Hydrolytic degradation by-products associated with the constitutive monomers 2,2
      bis [4-(2-hydroxy-3-methacryloxypropoxy) phenyl] propane (bis-GMA), bisphenol A
      polyethylene glycol diether dimethacrylate (bis-EMA), and triethylene glycol
      dimethacrylate (TEDGMA) used in dental restorative composites include bis-hydroxy
      propoxyphenyl propane (bis-HPPP), ethoxylated bisphenol A (E-bisPA), methacrylic
      acid (MA), and triethylene glycol (TEG). These products are generated from the
      interaction of human salivary esterases with the composites. Recent findings have
      indicated that TEGDMA has the ability to modulate oral bacteria but it is unclear
      which components of TEGDMA are related to the observed effects. The objective of
      the current study was to investigate the influence of TEGDMA derived degradation
      products MA and TEG on the growth of three strains of oral bacteria: S. mutans
      strains NG8 and JH1005, and S. salivarius AT2. Bacterial growth rates were
      measured at 37 degrees C, and pH values of 5.5 (representative of cariogenic
      state) or 7.0 at concentrations of 0-50mmol/l for MA (Sigma, US) and 0-100mmol/l
      for TEG (Sigma, US). It was found that at pH 5.5 TEG significantly stimulated the
      growth of both S. mutans strains ( p<0.05 ) in the concentration range of 0.5
      10.0mmol/l and stimulated the growth of S. salivarius AT2 for the entire
      concentration range tested (p<0.05). TEG (above 50mmol/1) did not significantly
      affect the doubling times of S. salivarius at pH of 7.0 and it inhibited the
      growth of both S. mutans strains above 50mmol/l at the same pH value. At pH 5.5
      MA inhibited the growth of all three strains with increasing concentration. At
      neutral pH, the growth of S. mutans NG8 strain was significantly reduced by MA (
      p<0.05 ) above 10mmol/l. In summary, these results indicate that TEG and MA
      modulate the growth rate of important oral bacteria in a concentration and pH
      dependent manner.

PMID- 15142728
TI  - Fabrication and characterization of bioactive wollastonite/PHBV composite
      scaffolds.
AB  - Composite scaffolds of polyhydroxybutyrate-polyhydroxyvalerate (PHBV) with
      bioactive wollastonite were fabricated by a compression moulding, thermal
      processing, and salt particulate leaching method. Structure and mechanical
      properties of the scaffolds were determined. The bioactivity of the composites
      was evaluated by soaking in a simulated body fluid (SBF), and the formation of
      the hydroxyapatite (HAp) layer was determined by Scanning Electron Microscope
      (SEM) and Energy-Dispersive Spectrometer (EDS). The results showed that the
      wollastonite/PHBV composites were bioactive as it induced the formation of HAp on
      the surface of the composite scaffolds after soaking in SBF for 14 days. In
      addition, the measurements of the water contact angles suggested that
      incorporation of wollastonite into PHBV could improve the hydrophilicity of the
      composites and the enhancement was dependent on the wollastonite content.
      Furthermore, the pH and ion concentration changes of SBF solutions with composite
      scaffolds showed that the composites released Ca and Si ions, which could
      neutralize the acidic by-products of the PHBV and stabilize the pH of the SBF
      solutions between 7.2 and 7.8 within a 3-week soaking period. All of these
      results suggest that the incorporation of wollastonite was a useful approach to
      obtain composite scaffolds with improved properties.

PMID- 15142729
TI  - Preparation of collagen/calcium phosphate multilayer sheet using enzymatic
      mineralization.
AB  - The multilayer sheets (2-10 layers), which consisted of alternately cumulated
      collagen and calcium phosphate layers with the thickness of 6-8microm in each
      layer, were prepared. The inorganic layer was mineralized by means of an alkaline
      phosphatase-catalyzed hydrolysis of water-soluble phosphate esters in the
      presence of calcium ions. The calcium phosphate, which was formed on the
      collagen, was assayed as a mixture of hydroxyapatite (main) and amorphous calcium
      phosphate. The multilayer sheets were not only strong mechanically but also
      semitransparent and flexible in a dry state. Furthermore, the collagen/calcium
      phosphate multilayer sheets did not swell in water to keep the original
      morphology. As a scaffold, the sheets having the calcium phosphate layer on the
      top supported the attachment and growth of L929 fibroblast cells. The enzymatic
      mineralization and the collagen/calcium phosphate composite sheets were discussed
      in conjunction with physicochemical and biological properties.

PMID- 15142730
TI  - Intercalation behavior and tensile strength of DNA-lipid films for the dental
      application.
AB  - In this study, we prepared DNA-lipid films and examined their intercalation
      behavior and tensile strength as an indicator for usefulness as a dental
      material. The lipids were synthesized from the reaction of glycine, l-alanine, or
      l-glutamic acid with n-alkyl alcohol in the presence of p-toluenesulfonic acid.
      The self-standing, water-insoluble DNA-lipid films were prepared by casting the
      DNA-lipid complex from chloroform/ethanol solution. The DNA-lipid films formed
      intercalation complexes with ethidium bromide. This indicates that DNA-lipid
      films maintain a double helical structure. The tensile strengths of DNA films
      were 0.8-2.4MPa and were compatible with a commercially available material
      (Membrane) for guided tissue regeneration in dental use. We conclude that DNA
      lipid films have potential for use as a material for the surface treatment of
      implanted materials or as a bone-guiding scaffold for dental application.

PMID- 15142731
TI  - The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive
      polycaprolactone scaffolds.
AB  - Our strategy entails investigating the influence of varied concentrations (0, 10,
      100 and 1000ng/ml) of human recombinant bone morphogenetic protein-2 (rhBMP-2) on
      the osteogenic expression of canine osteoblasts, seeded onto poly-caprolactone
      20% tricalcium phosphate (PCL-TCP) scaffolds in vitro. Biochemical assay revealed
      that groups with rhBMP-2 displayed an initial burst in cell growth that was not
      dose-dependent. However, after 13 days, cell growth declined to a value similar
      to control. Significantly less cell growth was observed for construct with
      1000ng/ml of rhBMP-2 from 20 days onwards. Confocal microscopy confirmed
      viability of osteoblasts and at day 20, groups seeded with rhBMP-2 displayed
      heightened cell death as compared to control. Phase contrast and scanning
      electron microscopy revealed that osteoblasts heavily colonized surfaces, rods
      and pores of the PCL-TCP scaffolds. This was consistent for all groups. Finally,
      Von Kossa and osteocalcin assays demonstrated that cells from all groups
      maintained their osteogenic phenotype throughout the experiment. Calcification
      was observed as early as four days after stimulation for groups seeded with rhBMP
      2. In conclusion, rhBMP-2 seems to enhance the differentiated function of canine
      osteoblasts in a non-dose dependent manner. This resulted in accelerated
      mineralization, followed by death of osteoblasts as they underwent terminal
      differentiation. Notably, PCL-TCP scaffolds seeded only with canine osteoblasts
      could sustain excellent osteogenic expression in vitro. Hence, the synergy of PCL
      with bioactive TCP and rhBMP-2 in a novel composite scaffold, could offer an
      exciting approach for bone regeneration.

PMID- 15142732
TI  - In vitro assessment of cell penetration into porous hydroxyapatite scaffolds with
      a central aligned channel.
AB  - There is a clinical need for synthetic scaffolds that promote bone regeneration.
      A common problem encountered when using scaffolds in tissue engineering is the
      rapid formation of tissue on the outer edge of the scaffold whilst the tissue in
      the centre becomes necrotic. To address this, the scaffold design should improve
      nutrient and cell transfer to the scaffold centre. In this study, hydroxyapatite
      scaffolds with random, open porosity (average pore size of 282+/-11microm,
      average interconnecting window size of 72+/-4microm) were manufactured using a
      modified slip-casting methodology with a single aligned channel inserted into the
      centre. By varying the aligned channel diameter, a series of scaffolds with
      channel diameters ranging from 170 to 421microm were produced. These scaffolds
      were seeded with human osteosarcoma (HOS TE85) cells and cultured for 8 days.
      Analysis of cell penetration into the aligned channels revealed that cell
      coverage increased with increasing channel diameter; from 22+/-3% in the
      170microm diameter channel to 38+/-6% coverage in the 421microm channel. Cell
      penetration into the middle section of the 421microm diameter channel (average
      cell area coverage 121x10(3)+/-32x10(3)microm(2)) was significantly greater than
      that observed within the 170microm channel (average cell area coverage 26x10(3)+/
      6x10(3)microm(2)). In addition, the data presented demonstrates that the minimum
      channel (or pore) diameter required for cell penetration into such scaffolds is
      approximately 80microm. These results will direct the development of scaffolds
      with aligned macroarchitecture for tissue engineering bone.

PMID- 15142733
TI  - Alpha-tocopherol-doped irradiated UHMWPE for high fatigue resistance and low
      wear.
AB  - Longevity of total joints has been compromised by wear and fatigue of ultrahigh
      molecular weight polyethylene (UHMWPE) components. Crosslinking reduces UHMWPE
      wear, but combined with postirradiation melting, also reduces its fatigue
      strength, therefore limiting its use in high-stress applications. We hypothesized
      that a lipophilic antioxidant (alpha-tocopherol, alpha-T) can protect UHMWPE
      against oxidation eliminating the need for postirradiation melting of crosslinked
      UHMWPE and improve its fatigue strength. To test these hypotheses, 65- and 100
      kGy irradiated, alpha-T-doped and subsequently gamma-sterilized UHMWPE were used.
      (I) alpha-T-doped irradiated UHMWPEs showed significantly lower oxidation levels
      (0.48+/-0.25 and 0.44+/-0.06) compared to 100-kGy irradiated UHMWPE (3.74+/-0.16)
      after 5 weeks of accelerated aging at 80 degrees C in air. (II) Wear rate of
      alpha-T-doped irradiated UHMWPE (1.9+/-0.5, and 0.9+/-0.1mg/million cycles (MC)
      for 65- and 100-kGy irradiated UHMWPE, respectively) were comparable to that of
      100-kGy irradiated/melted UHMWPE (1.1+/-0.7mg/million cycles). (III) The stress
      intensity factor at crack inception ( DeltaKi) of 100-kGy irradiated UHMWPE
      increased significantly upon doping with alpha-T from 0.74 to 0.87MPam(1/2) (
      p<0.01 ). The DeltaKi for the 100-kGy irradiated and melted UHMWPE, currently in
      clinical use, was 0.55MPam(1/2). Doping with alpha-T eliminated the need for
      postirradiation melting to protect irradiated UHMWPE against long-term oxidation.
      The fatigue strength was improved by 58% for alpha-T-doped 100-kGy irradiated
      UHMWPE compared to irradiated and melted UHMWPE. The increase in oxidative
      stability of alpha-T-doped UHMWPE is attributed to the ability of alpha-T to
      react with peroxy free radicals on lipid chains and arrest the oxidation
      reactions. The improved fatigue strength is attributed to the increase in
      plasticity of UHMWPE due to the lipophilic nature of alpha-T.

PMID- 15142734
TI  - Reduced calcification of bioprostheses, cross-linked via an improved carbodiimide
      based method.
AB  - Glutaraldehyde fixation of bioprosthetic tissue has been used successfully for
      almost 40 years. However, it is generally recognized that glutaraldehyde fixation
      of bioprostheses is associated with the occurrence of calcification. Accordingly,
      many efforts have been undertaken to develop techniques for the fixation of
      bioprostheses, which will not lead to calcification. Here we describe a new
      improved carbodiimide based cross-linking method. Rather than cross-linking the
      tissue through its free primary amine groups, these groups were first blocked
      with butanal and the tissue was then cross-linked by means of carbodiimide
      activation of tissue carboxylic acid groups followed by a reaction with a
      poly(propylene glycol)bis 2-(aminopropyl) ether, (Jeffamine trade mark ). It was
      demonstrated that cross-linked porcine leaflets had a calcification of less than
      1mg/g tissue after 8 weeks sub-dermal implantion in rats. Furthermore, aortic
      wall calcification was reduced to 50mg/g, compared to standard glutaraldehyde
      fixed tissue, which showed 120mg/g tissue calcification in the 8 weeks
      calcification model used.

PMID- 15142735
TI  - A new method for isolation of polyethylene wear debris from tissue and synovial
      fluid.
AB  - Sub-micron-sized ultrahigh molecular-weight polyethylene (PE) debris is generated
      in the joint space as a result of articulation and cyclic loading of an
      orthopaedic implant. Its characterization requires isolation and subsequent
      analysis by ultra-structural methods. An innovative method based on the digestion
      of paraffin-embedded tissue samples was proposed. Tissue slices were digested
      with sodium hypochlorite directly on polycarbonate filter. The same procedure
      could be applied also to fresh synovial fluid. Plastic particles were not lost or
      damaged during treatment. Chemical identification of particles was done by micro
      Raman spectroscopy that confirmed purity of retrieved PE particles. Size and
      shape of PE particles were characterised using scanning electron microscopy and
      were comparable in number and morphology to the retrieval by other authors.
      Equivalent diameter ranged from 0.48 to 0.95microm and particle number ranged
      from 9 to 23x10(9)/cm(3).

PMID- 15142736
TI  - Critical effect of cubic phase on aging in 3mol% yttria-stabilized zirconia
      ceramics for hip replacement prosthesis.
AB  - The isothermal tetragonal-to-monoclinic transformation of 3Y-TZP ceramics
      sintered at two different temperatures (1450 degrees C and 1550 degrees C) and
      duration (2 and 5h) is investigated at 134 degrees C in steam. Particular
      attention is paid to the presence of a cubic phase and its effect on isothermal
      aging. Sintering at 1550 degrees C can result in a significant amount of large
      cubic grains in the specimens, that have a detrimental impact on aging
      resistance, especially for the first stage of the aging process. Cubic grains
      appear to be enriched in yttrium, which in turn leads to a depletion of yttrium
      in the neighboring tetragonal grains. These grains will act as nucleation sites
      for tetragonal-to-monoclinic transformation. Even for specimens sintered at lower
      temperature, i.e. 1450 degrees C, the presence of a cubic phase is expected from
      the phase diagram, leading to a significant effect on aging sensitivity.

PMID- 15142737
TI  - Silver-coated megaendoprostheses in a rabbit model--an analysis of the infection
      rate and toxicological side effects.
AB  - Deep infection of megaprostheses remains a serious complication in orthopedic
      tumor surgery. Despite the use of systemic and local antibiotic prophylaxis the
      reported infection rate is between 5% and 35%. Silver-coated medical devices
      proved their effectiveness in reducing infections. The objective of this study
      was to examine in vivo the antimicrobial efficacy and possible side-effects of a
      silver-coated megaprosthesis. In a first study, 30 rabbits (15 titanium versus 15
      silver-coated Mutars-endoprostheses) were infected with Staphylococcus aureus. In
      a second study, toxicological side effects were analyzed in 10 rabbits with a
      silver-coated megaprosthesis. The silver group showed significantly (p<0.05)
      lower infection rates (7% versus 47%) in comparison with the titanium group.
      Measurements of the C-reactive-protein, neutrophilic leukocytes, rectal
      temperature and body weight showed significant (p<0.05) lower signs of
      inflammation in the silver group. The analysis of the silver concentration in
      blood (median 1.883ppb) and in organs (0.798-86.002ppb) showed elevated silver
      concentrations without pathologic changes in laboratory parameters and without
      histological changes of organs. In conclusion, the new silver-coated Mutars
      megaprosthesis resulted in reduced infection rates without toxicological side
      effects, suggesting that this prosthesis might be a promising device in tumor
      surgery exhibiting antimicrobial activity.

PMID- 15142738
TI  - Comparative evaluation of absorbable hemostats: advantages of fibrin-based
      sheets.
AB  - Bioactive hemostats and wound dressings consist of either inherently active
      materials or act as delivery vehicles which contain such materials. Fibrin is a
      natural hemostat and scaffold, guiding the direction of wound contraction and
      closure. In order to improve the ease of application of liquid fibrin glue, we
      have made a freeze-dried form of polymerized fibrin that supports hemostasis and
      wound healing. The bleeding from the middle ear artery of rabbits was found to be
      arrested instantaneously on application of fibrin sheets, even when the animal
      was heparinized systemically. As the fibrin sheet was found to be fragile,
      gelatin was incorporated to the sheet and thus the mechanical stability was
      improved without compromising the hemostatic effect. The efficacy of the
      fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was
      compared with commercially available hemostats, Abgel (cross-linked gelatin) and
      Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was
      studied by analyzing the liver tissue 15 days after application. While the
      hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel
      and Abgel were not capable of arresting the bleeding quickly. Gross analysis of
      tissue on the 15th day of application, visibly, Abgel was not only degraded but
      resulted in severe adhesions of internal organs and histologically capsule
      formation around the implant was evident. Though Surgicel was also seen as cream
      soft material on the site of application that joined two pieces of liver, there
      was no adhesion of other internal organs and histologically, immune reaction and
      foreign-body-type giant cells were present in large amounts. Fibrin was not found
      grossly on application site whereas fibrin-gelatin was seen as a small white
      spot. Granulation tissue formation and cell migration into the fibrin-based
      sheets were evident, and therefore, fibrin-based sheets are not only efficient
      hemostats but showed optimum degradation and wound healing.

PMID- 15142739
TI  - Modelling cellular and tissue function.

PMID- 15142740
TI  - A comparison of three models of the inositol trisphosphate receptor.
AB  - The inositol (1,4,5)-trisphosphate receptor (IPR) plays a crucial role in calcium
      dynamics in a wide range of cell types, and is often a central feature in
      quantitative models of calcium oscillations and waves. We compare three
      mathematical models of the IPR, fitting each of them to the same data set to
      determine ranges for the parameter values. Each of the fits indicates that fast
      activation of the receptor, followed by slow inactivation, is an important
      feature of the model, and also that the speed of inositol trisphosphate IP3
      binding cannot necessarily be assumed to be faster than Ca2+ activation. In
      addition, the model which assumed saturating binding rates of Ca2+ to the IPR
      demonstrated the best fit. However, lack of convergence in the fitting procedure
      indicates that responses to step increases of Ca2+ and IP3 provide insufficient
      data to determine the parameters unambiguously in any of the models.

PMID- 15142741
TI  - Analysing cardiac excitation-contraction coupling with mathematical models of
      local control.
AB  - Cardiac excitation-contraction (E-C) coupling describes the process that links
      sarcolemmal Ca2+ influx via L-type Ca2+ channels to Ca2+ release from the
      sarcoplasmic reticulum via ryanodine receptors (RyRs). This process has proven
      difficult to study experimentally, and complete descriptions of how the cell
      couples surface membrane and intracellular signal transduction proteins to
      achieve both stable and sensitive intracellular calcium release are still
      lacking. Mathematical models provide a framework to test our understanding of how
      this is achieved. While no single model is yet capable of describing all features
      of cardiac E-C coupling, models of increasing complexity are revealing unexpected
      subtlety in the process. In particular, modelling has established a general
      failure of 'common-pool' models and has emphasized the requirement for 'local
      control' so that microscopic sub-cellular domains can separate local behaviour
      from the whole-cell average (common-pool) behaviour. The micro-architecture of
      the narrow diadic cleft in which the local control takes place is a key factor in
      determining local Ca2+ dynamics. There is still considerable uncertainty about
      the number of Ca2+ ions required to open RyRs within the cleft and various gating
      models have been proposed, many of which are in reasonable agreement with
      available experimental data. However, not all models exhibit a realistic voltage
      dependence of E-C coupling gain. Furthermore, it is unclear which model features
      are essential to producing reasonable gain properties. Thus, despite the success
      of local-control models in explaining many features of cardiac E-C coupling, more
      work will be needed to provide a sound theoretical basis of cardiac E-C coupling.

PMID- 15142742
TI  - Modeling the isolated cardiac myocyte.
AB  - Computer modeling of cardiac myocytes has flourished in recent years. Models have
      evolved from mathematical descriptions of ionic channels alone to more
      sophisticated formulations that include calcium transport mechanisms, ATP
      production and metabolic pathways. The increased complexity is fueled by the new
      data available in the field. The continuous production of experimental data has
      led to the evolution of increasingly refined descriptions of the phenomena by
      modelers. Integrating the numerous systems involved in cardiac myocyte
      homeostasis makes the use of computer models necessary due to the unreliability
      of intuitive approaches. However the complexity of the model should not imply a
      cumbersome operation of the program. As with any tool, computer models have to be
      easy to operate or their strength will be diminished and potential users will not
      benefit fully from them. The contribution of the computer modeler to their
      respective biological fields will be more successful and enduring if modelers
      devote sufficient time to implement their equations into a model with user
      friendly characteristics.

PMID- 15142743
TI  - Approaches to modeling crossbridges and calcium-dependent activation in cardiac
      muscle.
AB  - While the primary function of the heart is a pump, ironically, the development of
      myofilament models that predict developed force have generally lagged behind the
      modeling of the electrophysiological and Ca2+-handling aspects of heart cells. A
      major impediment is that the basic events in force generating actin-myosin
      interactions are still not well understood and quantified despite advanced
      techniques that can probe molecular levels events and identify numerous energetic
      states. As a result, the modeler must decide how to best abstract the many
      identified states into useful models with an essential tradeoff in the level of
      complexity. Namely, complex models map more directly to biophysical states but
      experimental data does not yet exist to well constrain the rate constants and
      parameters. In contrast, parameters can be better constrained in simpler, lumped
      models, but the simplicity may preclude versatility and extensibility to other
      applications. Other controversies exist as to why the activation of the actin
      myosin is so steeply dependent on activator Ca2+. More specifically steady-state
      force-[Ca2+] (F-Ca) relationships are similar to Hill functions, presumably as
      the result of cooperative interactions between neighboring crossbridges and/or
      regulatory proteins. We postulate that mathematical models must contain explicit
      representation of nearest-neighbor cooperative interactions to reproduce F-Ca
      relationships similar to experimental measures, whereas spatially compressing,
      mean-field approximation used in most models cannot. Finally, a related
      controversy is why F-Ca relationships show increased Ca2+ sensitivity as
      sarcomere length (SL) increases. We propose a model that suggests that the length
      dependent effects can result from an interaction of explicit nearest-neighbor
      cooperative mechanisms and the number of recruitable crossbridges as a function
      of SL.

PMID- 15142744
TI  - Receptors, sparks and waves in a fire-diffuse-fire framework for calcium release.
AB  - Calcium ions are an important second messenger in living cells. Indeed calcium
      signals in the form of waves have been the subject of much recent experimental
      interest. It is now well established that these waves are composed of elementary
      stochastic release events (calcium puffs or sparks) from spatially localised
      calcium stores. The aim of this paper is to analyse how the stochastic nature of
      individual receptors within these stores combines to create stochastic behaviour
      on long time-scales that may ultimately lead to waves of activity in a spatially
      extended cell model. Techniques from asymptotic analysis and stochastic phase
      plane analysis are used to show that a large cluster of receptor channels leads
      to a release probability with a sigmoidal dependence on calcium density. This
      release probability is incorporated into a computationally inexpensive model of
      calcium release based upon a stochastic generalisation of the fire-diffuse-fire
      (FDF) threshold model. Numerical simulations of the model in one and two
      dimensions (with stores arranged on both regular and disordered lattices)
      illustrate that stochastic calcium release leads to the spontaneous production of
      calcium sparks that may merge to form saltatory waves. Illustrations of spreading
      circular waves, spirals and more irregular waves are presented. Furthermore,
      receptor noise is shown to generate a form of array enhanced coherence resonance
      whereby all calcium stores release periodically and simultaneously.

PMID- 15142745
TI  - A multi-scaled approach for simulating chemical reaction systems.
AB  - In this paper we give an overview of some very recent work, as well as presenting
      a new approach, on the stochastic simulation of multi-scaled systems involving
      chemical reactions. In many biological systems (such as genetic regulation and
      cellular dynamics) there is a mix between small numbers of key regulatory
      proteins, and medium and large numbers of molecules. In addition, it is important
      to be able to follow the trajectories of individual molecules by taking proper
      account of the randomness inherent in such a system. We describe different types
      of simulation techniques (including the stochastic simulation algorithm, Poisson
      Runge-Kutta methods and the balanced Euler method) for treating simulations in
      the three different reaction regimes: slow, medium and fast. We then review some
      recent techniques on the treatment of coupled slow and fast reactions for
      stochastic chemical kinetics and present a new approach which couples the three
      regimes mentioned above. We then apply this approach to a biologically inspired
      problem involving the expression and activity of LacZ and LacY proteins in E.
      coli, and conclude with a discussion on the significance of this work.

PMID- 15142746
TI  - Reaction kinetics in intracellular environments with macromolecular crowding:
      simulations and rate laws.
AB  - We review recent evidence illustrating the fundamental difference between
      cytoplasmic and test tube biochemical kinetics and thermodynamics, and showing
      the breakdown of the law of mass action and power-law approximation in in vivo
      conditions. Simulations of biochemical reactions in non-homogeneous media show
      that as a result of anomalous diffusion and mixing of the biochemical species,
      reactions follow a fractal-like kinetics. Consequently, the conventional
      equations for biochemical pathways fail to describe the reactions in in vivo
      conditions. We present a modification to fractal-like kinetics following the Zipf
      Mandelbrot distribution which will enable the modelling and analysis of
      biochemical reactions occurring in crowded intracellular environments.

PMID- 15142747
TI  - Mechanistic systems models of cell signaling networks: a case study of myocyte
      adrenergic regulation.
AB  - Signal transduction networks coordinate a wide variety of cellular functions,
      including gene expression, metabolism, and cell fate processes. Understanding
      biological networks quantitatively is a major challenge to post-genomic biology,
      and mechanistic systems models will be crucial for this task. Here, we review
      approaches towards developing mechanistic systems models of established cell
      signaling networks. The ability of mechanistic system models to generate testable
      biological hypotheses and experimental strategies is discussed. As a case study
      of model development and analysis, we examined the functional roles of
      phospholamban, the L-type calcium channel, the ryanodine receptor, and troponin I
      phosphorylation upon beta-adrenergic stimulation in the rat ventricular myocyte.
      Model analysis revealed that while protein kinase A-mediated phosphorylation of
      the ryanodine receptor greatly increases its calcium sensitivity, calcium
      autoregulation may adapt quickly by negating potential increases in
      contractility. Systematic combinations of in silico perturbations supported the
      conclusion that phospholamban phosphoregulation is the primary mechanism for
      increased sarcoplasmic reticulum load and calcium relaxation rate during beta
      adrenergic stimulation, while both phospholamban and the L-type calcium channel
      contribute to increased systolic calcium. Combined with detailed experimental
      studies, mechanistic systems models will be valuable for developing a
      quantitative understanding of cell signaling networks.

PMID- 15142749
TI  - A gradient model of cardiac pacemaker myocytes.
AB  - We have formulated a spatial-gradient model of action potential heterogeneity
      within the rabbit sinoatrial node (SAN), based on cell-specific ionic models of
      electrical activity from its central and peripheral regions. The ionic models are
      derived from a generic cell model, incorporating five background and exchange
      currents, and seven time-dependent currents based on three- or four-state Markov
      schemes. State transition rates are given by non-linear sigmoid functions of
      membrane potential. By appropriate selection of parameters, the generic model is
      able to accurately reproduce a wide range of action potential waveforms observed
      experimentally. Specifically, the model can fit recordings from central and
      peripheral regions of the SAN with RMS errors of 0.3987 and 0.7628 m V,
      respectively. Using a custom least squares parameter optimisation routine, we
      have constructed a spatially-varying gradient model that exhibits a smooth
      transition in action potential characteristics from the central to the peripheral
      region, whilst ensuring individual membrane currents remain physiologically
      accurate. Smooth transition action potential characteristics include maximum
      diastolic potential, overshoot potential, upstroke velocity, action potential
      duration and cycle length. The gradient model is suitable for developing higher
      dimensional models of the right atrium, in which action potential heterogeneity
      within nodal tissue may be readily incorporated.

PMID- 15142748
TI  - Simulation of ATP metabolism in cardiac excitation-contraction coupling.
AB  - To obtain insights into the mechanisms underlying the membrane excitation and
      contraction of cardiac myocytes, we developed a computer model of excitation
      contraction coupling (Kyoto model: Jpn. J. Physiol. 53 (2003) 105). This model
      was further expanded by incorporating pivotal reactions of ATP metabolism; the
      model of mitochondrial oxidative phosphorylation by Korzeniewski and Zoladz
      (Biophys. Chem. 92 (2001) 17). The ATP-dependence of contraction, and creatine
      kinase and adenylate kinase were also incorporated. After minor modifications,
      the steady-state condition was well established for all the variables, including
      the membrane potential, contraction, and the ion and metabolite concentrations in
      sarcoplasmic reticulum, mitochondria and cytoplasm. Concentrations of major
      metabolites were close to the experimental data. Responses of the new model to
      anoxia were similar to experimental results of the P-31 NMR study in whole heart.
      This model serves as a prototype for developing a more comprehensive model of
      excitation-contraction-metabolism coupling.

PMID- 15142750
TI  - Current status and challenges in connecting models of erythrocyte metabolism to
      experimental reality.
AB  - Detailed kinetic models of human erythrocyte metabolism have served to summarize
      the vast literature and to predict outcomes from laboratory and "Nature's"
      experiments on this simple cell. Mathematical methods for handling the large
      array of nonlinear ordinary differential equations that describe the time
      dependence of this system are well developed, but experimental methods that can
      guide the evolution of the models are in short supply. NMR spectroscopy is one
      method that is non-selective with respect to analyte detection but is highly
      specific with respect to their identification and quantification. Thus time
      courses of metabolism are readily recorded for easily changed experimental
      conditions. While the data can be simulated, the systems of equations are too
      complex to allow solutions of the inverse problem, namely parameter-value
      estimation for the large number of enzyme and membrane-transport reactions
      operating in situ as opposed to in vitro. Other complications with the modelling
      include the dependence of cell volume on time, and the rates of membrane
      transport processes are often dependent on the membrane potential. These matters
      are discussed in the light of new modelling strategies.

PMID- 15142751
TI  - Results from modeling of B-Cell receptors binding to antigen.
AB  - In the late 80's, Dintzis et al. conducted an experiment which showed that T-Cell
      independent activation of B-cells needs high-valence antigen and happens only in
      a narrow range of antigen concentration. These experiments were believed to be
      explained by the "immunon" theory that requires that a minimum number of
      receptors need to be cross-linked to activate a cell. However, the immunon theory
      does not take into account receptor dynamics and cannot explain the lack of
      immune response at high antigen concentration or low antigen valence. We propose
      instead a simple, new mechanism for the T-Cell independent activation of B-Cell,
      which includes receptor endocytosis. Our model focuses on the fact that for the
      majority of antigens where the B-Cell is activated with T-Cell help, the kinetic
      parameters for binding, unbinding and endocytosis must be tuned so that there is
      an equilibrium between the number of receptors bound on the surface of the B-Cell
      and the number of antigen-bound receptors endocytosed. This equilibrium mechanism
      is probably generic and will also occur even when the B-Cell is activated by
      antigen without T-Cell help. By computer modeling, we show that if we accept this
      hypothesis of the requirement for equilibrium between the two mechanisms of
      binding and endocytosis, then we can explain both the valence cutoff and the low
      and high zone tolerance seen in the Dintzis experiment.

PMID- 15142752
TI  - Modelling cell population growth with applications to cancer therapy in human
      tumour cell lines.
AB  - In this paper we present an overview of the work undertaken to model a population
      of cells and the effects of cancer therapy. We began with a theoretical one
      compartment size structured cell population model and investigated its asymptotic
      steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA
      21 (2004) 49). However these size distributions are not similar to the DNA (size)
      distributions obtained experimentally via the flow cytometric analysis of human
      tumour cell lines (data obtained from the Auckland Cancer Society Research
      Centre, New Zealand). In our one compartment model, size was a generic term, but
      in order to obtain realistic steady size distributions we chose size to be DNA
      content and devised a multi-compartment mathematical model for the cell division
      cycle where each compartment corresponds to a distinct phase of the cell cycle
      (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment
      describing the possible induction of apoptosis (cell death) from mitosis phase
      (Modelling cell death in human tumour cell lines exposed to anticancer drug
      paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model
      to flow cytometric data of a melanoma cell line where the anticancer drug,
      paclitaxel, had been added. The model gives a dynamic picture of the effects of
      paclitaxel on the cell cycle. We hope to use the model to describe the effects of
      other cancer therapies on a number of different cell lines.

PMID- 15142753
TI  - Modelling general anaesthesia as a first-order phase transition in the cortex.
AB  - Since 1997 we have been developing a theoretical foundation for general
      anaesthesia. We have been able to demonstrate that the abrupt change in brain
      state brought on by anaesthetic drugs can be characterized as a first-order phase
      transition in the population-average membrane voltage of the cortical neurons.
      The theory predicts that, as the critical point of phase change into
      unconsciousness is approached, the electrical fluctuations in cortical activity
      will grow strongly in amplitude while slowing in frequency, becoming more
      correlated both in time and in space. Thus the bio-electrical change of brain
      state has deep similarities with thermodynamic phase changes of classical
      physics. The theory further predicts the existence of a second critical point,
      hysteretically separated from the first, corresponding to the return path from
      comatose unconsciousness back to normal responsiveness. There is a steadily
      accumulating body of clinical evidence in support of all of the phase-transition
      predictions: low-frequency power surge in EEG activity; increased correlation
      time and correlation length in EEG fluctuations; hysteresis separation, with
      respect to drug concentration, between the point of induction and the point of
      emergence.

PMID- 15142754
TI  - Development of models of active ion transport for whole-cell modelling: cardiac
      sodium-potassium pump as a case study.
AB  - This study presents a method for the reduction of biophysically-based kinetic
      models for the active transport of ions. A lumping scheme is presented which
      exploits the differences in timescales associated with fast and slow transitions
      between model states, while maintaining the thermodynamic properties of the
      model. The goal of this approach is to contribute to modelling of the effects of
      disturbances to metabolism, associated with ischaemic heart disease, on cardiac
      cell function. The approach is illustrated for the sodium-potassium pump in the
      myocyte. The lumping scheme is applied to produce a 4-state representation from
      the detailed 15-state model of Lauger and Apell, Eur. Biophys. J. 13 (1986) 309,
      for which the principles of free energy transduction are used to link the free
      energy released from ATP hydrolysis (deltaGATP) to the transition rates between
      states of the model. An iterative minimisation algorithm is implemented to
      determine the transition rate parameters based on the model fit to experimental
      data. Finally, the relationship between deltaGATP and pump cycling direction is
      investigated and compared with recent experimental findings.

PMID- 15142755
TI  - Parameter estimation in cardiac ionic models.
AB  - We examine the problem of parameter estimation in mathematical models of
      excitable cell cardiac electrical activity using the well-known Beeler-Reuter
      (1977) ionic equations for the ventricular action potential. The estimation
      problem can be regarded as equivalent to the accurate reconstruction of ionic
      current kinetics and amplitudes in an excitable cell model, given only action
      potential experimental data. We show that in the Beeler-Reuter case, all ionic
      currents may be reasonably reconstructed using an experimental design consisting
      of action potential recordings perturbed by pseudo-random injection currents. The
      Beeler-Reuter model was parameterised into 63 parameters completely defining all
      membrane current amplitudes and kinetics. Total membrane current was fitted to
      model-generated experimental data using a 'data-clamp' protocol. The experimental
      data consisted of a default action-potential waveform and an optional series of
      perturbed waveforms generated by current injections. Local parameter
      identifiability was ascertained from the reciprocal condition value (1/lambda) of
      the Hessian at the known solution. When fitting to a single action potential
      waveform, the model was found to be over-determined, having a 1/lambda value of
      approximately 3.6e-14. This value improved slightly to approximately 1.4e-10 when
      an additional 2 perturbed waveforms were included in the fitting process,
      suggesting that the additional data did not overly improve the identifiability
      problem. The additional data, however, did allow the accurate reconstruction of
      all ionic currents. This indicates that by appropriate experimental design, it
      may be possible to infer the properties of underlying membrane currents from
      observation of transmembrane potential waveforms perturbed by pseudo-random
      currents.

PMID- 15142756
TI  - CellML: its future, present and past.
AB  - Advances in biotechnology and experimental techniques have lead to the
      elucidation of vast amounts of biological data. Mathematical models provide a
      method of analysing this data; however, there are two issues that need to be
      addressed: (1) the need for standards for defining cell models so they can, for
      example, be exchanged across the World Wide Web, and also read into simulation
      software in a consistent format and (2) eliminating the errors which arise with
      the current method of model publication. CellML has evolved to meet these needs
      of the modelling community. CellML is a free, open-source, eXtensible markup
      language based standard for defining mathematical models of cellular function. In
      this paper we summarise the structure of CellML, its current applications
      (including biological pathway and electrophysiological models), and its future
      development--in particular, the development of toolsets and the integration of
      ontologies.

PMID- 15142758
TI  - Propagation of normal beats and re-entry in a computational model of ventricular
      cardiac tissue with regional differences in action potential shape and duration.
AB  - There is substantial experimental evidence from studies using both intact tissue
      and isolated single cells to support the existence of different cell types within
      the ventricular wall of the heart, each possessing different electrical
      properties. However other studies have failed to find these differences, and
      instead support the idea that electrical coupling in vivo between regions with
      different cell types smoothes out differences in action potential shape and
      duration. In this study we have used a computational model of electrical
      activation in heterogenous 2D and 3D cardiac tissue to investigate the
      propagation of both normal beats and arrhythmias. We used the Luo-Rudy dynamic
      model for guinea pig ventricular cells, with simplified Ca2+ handling and
      transmural heterogeneity in IKs and Ito. With normal cell-to-cell coupling, a
      layer of M cells was not necessary for the formation of an upright T wave in the
      simulated electrocardiogram, and the amplitude and configuration of the T wave
      was not greatly affected by the thickness and configuration of the M cell layer.
      Transmural gradients in repolarisation pushed re-entrant waves with an intramural
      filament towards either the base or the apex of the ventricles, and caused
      transient break up of re-entry with a transmural filament.

PMID- 15142757
TI  - Towards whole-organ modelling of tumour growth.
AB  - Multiscale approaches to modelling biological phenomena are growing rapidly. We
      present here some recent results on the formulation of a theoretical framework
      which can be developed into a fully integrative model for cancer growth. The
      model takes account of vascular adaptation and cell-cycle dynamics. We explore
      the effects of spatial inhomogeneity induced by the blood flow through the
      vascular network and of the possible effects of p27 on the cell cycle. We show
      how the model may be used to investigate the efficiency of drug-delivery
      protocols.

PMID- 15142759
TI  - Electromechanical model of excitable tissue to study reentrant cardiac
      arrhythmias.
AB  - We introduce the concept of a contracting excitable medium that is capable of
      conducting non-linear waves of excitation that in turn initiate contraction.
      Furthermore, these kinematic deformations have a feedback effect on the
      excitation properties of the medium. Electrical characteristics resemble basic
      models of cardiac excitation that have been used to successfully study mechanisms
      of reentrant cardiac arrhythmias in electrophysiology. We present a computational
      framework that employs electromechanical and mechanoelectric feedback to couple a
      three-variable FitzHugh-Nagumo-type excitation-tension model to the non-linear
      stress equilibrium equations, which govern large deformation hyperelasticity.
      Numerically, the coupled electromechanical model combines a finite difference
      method approach to integrate the excitation equations, with a Galerkin finite
      element method to solve the equations governing tissue mechanics. We present
      example computations demonstrating various effects of contraction on stationary
      rotating spiral waves and spiral wave break. We show that tissue mechanics
      significantly contributes to the dynamics of electrical propagation, and that a
      coupled electromechanical approach should be pursued in future
      electrophysiological modelling studies.

PMID- 15142760
TI  - Modelling gastrointestinal bioelectric activity.
AB  - The development of an anatomically realistic biophysically based model of the
      human gastrointestinal (GI) tract is presented. A major objective of this work is
      to develop a modelling framework that can be used to integrate the physiological,
      anatomical and medical knowledge of the GI system. The anatomical model was
      developed by fitting derivative continuous meshes to digitised data taken from
      images of the visible man. Structural information, including fibre distributions
      of the smooth muscle layers and the arrangement of the networks of interstitial
      cells of Cajal, were incorporated using published information. A continuum
      modelling framework was used to simulate electrical activity from the single cell
      to the whole organ and body. Also computed was the external magnetic field
      generated from the GI electrical activity. The set of governing equations were
      solved using a combination of numerical techniques. Activity at the (continuum)
      cell level was solved using a high-resolution trilinear finite element procedure
      that had been defined from the previously fitted C1 continuous anatomical mesh.
      Multiple dipolar sources were created from the excitation waves which were
      embedded within a coupled C1 continuous torso model to produce both the cutaneous
      electrical field and the external magnetic field. Initial simulations were
      performed using a simplified geometry to test the implementation of the numerical
      solution procedure. The numerical procedures were shown to rapidly converge with
      mesh refinement. In the process of this testing, errors in a long standing
      analytic solution were identified and are corrected in Appendix B. Results of
      single cell activity were compared to published results illustrating that the key
      features of the slow wave activity were successfully replicated. Simulations
      using a two-dimensional slice through the gastric wall produced slow wave
      activity that agreed with the known frequency and propagation characteristics.
      Three-dimensional simulations were also performed using the full stomach mesh and
      results illustrated the slow wave propagation throughout the stomach musculature.

PMID- 15142761
TI  - The IUPS Physiome Project: a framework for computational physiology.
AB  - The IUPS Physiome Project is an internationally collaborative open-source project
      to provide a public domain framework for computational physiology, including the
      development of modelling standards, computational tools and web-accessible
      databases of models of structure and function at all spatial scales. A number of
      papers in this volume deal with the development of specific mathematical models
      of physiological processes. This paper stands back from the detail of individual
      models and reviews the current state of the IUPS Physiome Project including organ
      and organ system continuum models, the interpretation of constitutive law
      parameters in terms of micro-structural models, and markup languages for
      standardizing cellular processes. Some current practical applications of the
      physiome models are given and some of the challenges for the next 5 years of the
      Physiome Project at the level of organs, cells and proteins are proposed.

PMID- 15142762
TI  - Review of selenium toxicity in the aquatic food chain.
AB  - In many environmental contaminant situations selenium has become the primary
      element of concern because of its bioaccumulative nature in food webs. Initial
      concerns about selenium were related to fish kills at Belews Lake, NC, Martin
      Lake, TX, and Kesterson Reservoir, CA, and to bird deformities at Kesterson
      Reservoir. Additional concerns were identified under the National Irrigation
      Water Quality Program at Salton Sea, CA, Kendrick, WY, Stewart Lake, UT, and
      Grand Valley and Uncompahgre Valley, CO. Recent studies have raised concerns
      about selenium impacts on aquatic resources in Southeastern Idaho and British
      Columbia. The growing discomfort among the scientific community with a waterborne
      criterion has lead the US Environment Protection Agency to consider a tissue
      based criterion for selenium. Some aquatic ecosystems have been slow to recover
      from selenium contamination episodes. In recent years, non-governmental
      researchers have been proposing relatively high selenium thresholds in diet and
      tissue relative to those proposed by governmental researchers. This difference in
      opinions is due in part to the selection of datasets and caveats in selecting
      scientific literature. In spite of the growing selenium literature, there are
      needs for additional research on neglected organisms. This review also discusses
      the interaction of selenium with other elements, inconsistent effects of selenium
      on survival and growth of fish, and differences in depuration rates and
      sensitivity among species.

PMID- 15142763
TI  - Arsenic and other elements in hair, nails, and skin-scales of arsenic victims in
      West Bengal, India.
AB  - For the first time, biological tissues (hair, nails, and skin-scales) of arsenic
      victims from an arsenic affected area of West Bengal (WB), India were analyzed
      for trace elements. Analysis was carried out by inductively coupled plasma-mass
      spectrometry (ICP-MS) for 10 elements (As, Se, Hg, Zn, Pb, Ni, Cd, Mn, Cu, and
      Fe). A microwave digester was used for digestion of the tissue samples. To
      validate the method, certified reference materials--human hair (GBW 07601) and
      bovine muscle (CRM 8414)--were analyzed for all elements. The W test was used to
      study the normal/log normal distribution for each element in the tissue samples.
      For hair (n=44) and nails (n=33), all elements show log-normal distribution. For
      skin-scale samples (n=11), data are not sufficient to provide the information
      about the trend. Geometric mean, standard error, and range for each element were
      presented and compared with literature values for other populations. This study
      reveals the higher levels of toxic elements As, Mn, Pb, and Ni in the tissue
      samples compared with available values in the literature. The elevated levels of
      these toxic metals in the tissues may be due to exposure of these elements
      through drinking water and food. The correlations of Mn and Ni with other
      essential elements, e.g. Fe, Cu, Zn, suggest that Mn and Ni may substitute for
      those elements in hair, nails, and skin-scales. However, correlation represents
      the relation between two elements only and does not take into consideration of
      the presence of other elements. Principle component analysis was applied to
      explain the behavior among the elements present in hair and nails. This study
      reveals that in the arsenic-affected areas of WB, the concentrations of other
      toxic elements in drinking water and foodstuff should be monitored to evaluate
      the arsenic poisoning.

PMID- 15142764
TI  - Heterogeneity of cadmium concentration in soil as a source of uncertainty in
      plant uptake and its implications for human health risk assessment.
AB  - The major route of exposure of humans to the toxic element cadmium (Cd) is via
      the consumption of vegetables homegrown on Cd contaminated soil. It is well known
      that soil pH is one of the main soil properties controlling bioavailability of Cd
      in plants. This is acknowledged in human health risk assessment models that
      incorporate pH dependant concentration factors (CF=plant Cd/soil Cd). However,
      variation in spatial heterogeneity of nutrients and heavy metals in soil can have
      a profound effect on plant performance and uptake of nutrients and heavy metals.
      Here we show for lettuce (variety Crispino) that variation in plant-scale
      heterogeneity of Cd in soil affects bioavailability and hence CF by a factor of
      2. Plant yield is also significantly affected. This has important implications
      for both human health risk assessment, as variation in CF affects predicted
      exposure, and for phytoremediation where an optimal combination of plant yield
      and contaminant accumulation is required.

PMID- 15142765
TI  - Mortality of globally threatened Sarus cranes Grus antigon from monocrotophos
      poisoning in India.
AB  - Globally threatened Sarus cranes Grus antigon are resident at Keoladeo National
      Park World Heritage site and the surrounding area near Bharatpur, Western
      Rajasthan, India. In winter, they are joined by c. 200 wintering common cranes
      Grus grus. On 23 November 2000, 15 Sarus cranes and three common cranes were
      found dead in a field adjacent to the park, where wheat seed had been sown the
      previous day. Chemical analyses of seed samples from the field and the cranes'
      alimentary tract contents identified residues of the organophosphate insecticide
      monocrotophos. Monocrotophos concentrations of 0.8 and 1.8 ppm were found in
      wheat samples, and 0.2-0.74 ppm (x=0.33) in the alimentary tract contents of five
      of the seven cranes examined. No other organophosphate or organochlorine
      pesticides were detected. We conclude that the cranes died from monocrotophos
      poisoning after eating treated seed. We discuss similar incidents of avian
      mortality, and recommend that measures be taken to reduce these.

PMID- 15142766
TI  - The influence of total organic carbon (TOC) on the relationship between acid
      neutralizing capacity (ANC) and fish status in Norwegian lakes.
AB  - Acid neutralizing capacity (ANC) is the parameter most commonly used as chemical
      indicator for fish response to acidification. Empirical relationships between
      fish status of surface waters and ANC have been documented earlier. ANC is
      commonly calculated as the difference between base cations
      ([BC]=[Ca2+]+[Mg2+]+[N+]+[K+]) and strong acid anions ([SAA]=[SO4(2)-]+[NO3-]+[Cl
      ]). This is a very robust calculation of ANC, because none of the parameters
      incorporated are affected by the partial pressure of CO2, in contrast to the
      remaining major ions in waters, pH ([H+]), aluminum ([Aln+]), alkalinity ([HCO3
      /CO3(2)-]) and organic anions ([An-]). Here we propose a modified ANC calculation
      where the permanent anionic charge of the organic acids is assumed as a part of
      the strong acid anions. In many humic lakes, the weak organic acids are the
      predominant pH-buffering system. Because a significant amount of the weak organic
      acids have pK-values<3.0-3.5, these relatively strong acids will permanently be
      deprotonated in almost all natural waters (i.e. pH>4.5). This means that they
      will be permanently present as anions, equal to the strong acid inorganic anions,
      SO4(2)-, NO3- and Cl-. In the literature, natural organic acids are often
      described as triprotic acids with a low pK1 value. Assuming a triprotic model, we
      suggest to add 1/3 of the organic acid charge density to the strong acid anions
      in the ANC calculation. The suggested organic acid adjusted ANC (ANC(OAA)), is
      then calculated as follows: ANC(OAA)=[BC]-([SAA]+1/3CD*TOC) where TOC is total
      organic carbon (mg C L(-1)), and CD=10.2 is charge density of the organic matter
      (microeq/mg C), based on literature data from Swedish lakes. ANC(OAA) gives
      significant lower values of ANC in order to achieve equal fish status compared
      with the traditional ANC calculation. Using ANC(OAA) the humic conditions in
      lakes are better taken into account. This may also help explain observations of
      higher ANC needed to have reproducing fish populations in lakes with higher TOC
      concentrations.

PMID- 15142767
TI  - Extractability of metals and ecotoxicity of soils from two old wood impregnation
      sites in Finland.
AB  - Four metal-contaminated soil samples were classified using physical methods,
      extracted by selective extraction procedures and analyzed for chemical
      concentrations. De-ionized water, 0.01 mol/l barium chloride, 1 mol/l ammonium
      acetate and concentrated nitric acid were used as extraction solutions.
      Ecotoxicity of water extracts and soil samples was analyzed in order to describe
      the bioavailability of the contaminants. Samples from old wood impregnation
      plants contained high amounts of As, Cu, Cr and Zn, which originated from
      chromated copper arsenate, ammoniacal copper-zinc arsenate, and ammoniacal copper
      quaternary compound. Total As concentrations of the heavily contaminated samples
      varied from 752 to 4340 mg/kg, Cu concentrations from 339 to 2330 mg/kg, Cr
      concentrations from 367 to 2,140 mg/kg and Zn concentrations from 79 to 966
      mg/kg. The extractabilities of metals differed according to soil type, extractant
      and element. Cu and Zn were proposed to cause the highest toxicity in the water
      extracts of the soils. Ecotoxicity tests displayed rather high differences in
      sensitivity both for water extracts and for solid soil samples. Reproduction of
      Enchytraeus sp. was the most sensitive and seed germination of Lactuca sativa the
      least sensitive and the other tests were in decreasing order of sensitivity:
      Folsomia candida>reverse electron transport>MetPLATE>Toxichromotest>Allium cepa
      root growth>Lemna sp. growth. As a conclusion, polluted soils rich in sand retain
      heavy metals with less firm bindings, particularly in the case of Cu and Zn, than
      soils rich in clay, indicating that chemical methods for measuring the
      bioavailability of metals need to be optimized taking into account the soil type,
      acidity, redox state and the individual contaminants.

PMID- 15142769
TI  - Can climate change explain increases in DOC flux from upland peat catchments?
AB  - Long-term increases in DOC concentration in rivers draining areas of upland peat
      are a ubiquitous phenomenon in the UK. Several hypotheses have been proposed to
      explain these increases, but one compelling explanation is the observed long-term
      increase in temperature in UK uplands causing increases in peat decomposition
      rates, and increasing the depth of oxidation as evaporation increases depth to
      the water table. The study constructed an empirical model for water table depth
      and decomposition rate calibrated against observations from the Environmental
      Change Network monitoring site at Moor House in the North Pennines, UK. The study
      shows: (i) Depth of the water table has not changed significantly over a 30-year
      period, reflecting the fact that blanket peat is well buffered against climate
      change. (ii) Increases in temperature are responsible for a 12% increase in DOC
      production while an approximate 78% increase in DOC production has been observed.
      (iii) Overall DOC production is predicted to rise by 6% but observation suggests
      increases on the scale of 97%. (iv) The model inadequately represents changes in
      production and supply of DOC during periods of severe drought. The study shows
      that temperature change alone is insufficient to explain observed increases in
      DOC production. Alternative explanations for large increases in DOC production
      could include changes in land management, but an enzymic latch mechanism, i.e.
      derepression of anaerobic degradation, causing increased decomposition rates in
      response to severe drought is preferred.

PMID- 15142768
TI  - Combined effect of copper, cadmium, and lead upon Cucumis sativus growth and
      bioaccumulation.
AB  - Cucumis sativus (cucumber) was tested to assess an ecotoxicity in soils
      contaminated by the heavy metals copper (Cu), cadmium (Cd), and lead (Pb)
      separately and in combinations. The toxicity endpoint was plant growth, which was
      measured as shoot and root lengths after 5 day exposure. Sum of toxic unit (TU)
      at 50% inhibition for the mixture (EC50mix) was calculated from the dose (TU
      based)-response relationships by the Trimmed Spearman-Karber method. Binary metal
      combinations of Cu+Cd, Cu+Pb, and Cd+Pb produced all three types of interactions;
      concentration additive (EC50mix=1TU), synergistic (EC50mix<1TU), and antagonistic
      (EC50mix>1TU) responses. Ternary combination of Cu+Cd+Pb produced an antagonistic
      response for the growth of Cucumis sativus. Bioaccumulations of Cu, Cd, and Pb
      were observed in Cucumis sativus and the bioaccumulation of one metal was
      influenced by the presence of other metals in metal mixtures. In general,
      antagonistic and/or synergistic responses reflected bioaccumulation patterns in
      some binary combinations, but the patterns in mixtures were not always consistent
      with toxicity data. This study indicated that TU approach appears to be a good
      model to estimate the combined effect of metals in plant systems, and mixture
      toxicity may be closely-related to the bioaccumulation pattern within plants.
      Combined effects of mixtures have to be taken into account to ecological risk
      assessment.

PMID- 15142770
TI  - Biodiversity of epiphytic lichens and heavy metal contents of Flavoparmelia
      caperata thalli as indicators of temporal variations of air pollution in the town
      of Montecatini Terme (central Italy).
AB  - The results of a biomonitoring survey carried out in the town of Montecatini
      Terme (central Italy) in the period 1993-2000 using the biodiversity of epiphytic
      lichens and the accumulation of heavy metals in thalli of Flavoparmelia caperata
      as indicators of air pollution are reported. From 1993 to 2000, the mean ILD
      value for the whole study area increased from 18+/-18 to 42+/-22, the lowest ILD
      value increased from 0 to 11 and the highest ILD value increased from 67 to 84. A
      'lichen desert' was found only in 1993 and stations classified as 'natural' were
      lacking only in 1993 and 1996. Concentrations of all heavy metals decreased from
      1993 to 1999. It is concluded that vehicular traffic is the main source of
      atmospheric pollution in the study area. The most likely changes that may have
      caused lichen communities to improve and heavy metals to drop is conversion of
      heating systems to methane (abatement of SO2) and the use of unleaded gasoline
      (reduction of Pb). The present results showed that despite their slow growth
      rate, lichens respond rapidly to decreasing concentrations of air pollutants,
      allowing annual changes to be detected.

PMID- 15142771
TI  - Airborne viable, non-viable, and allergenic fungi in a rural agricultural area of
      India: a 2-year study at five outdoor sampling stations.
AB  - The information on airborne allergenic fungal flora in rural agricultural areas
      is largely lacking. Adequate information is not available to the bioaerosol
      researchers regarding the choice of single versus multiple sampling stations for
      the monitoring of both viable and non-viable airborne fungi. There is no long
      term study estimating the ratios of viable and non-viable fungi in the air and
      earlier studies did not focus on the fractions of airborne allergenic fungi with
      respect to the total airborne fungal load. To fill these knowledge gaps,
      volumetric paired assessments of airborne viable and non-viable fungi were
      performed in five outdoor sampling stations during two consecutive years in a
      rural agricultural area of India. Samples were collected at 10-day intervals by
      the Burkard Personal Slide Sampler and the Andersen Two-Stage Viable Sampler. The
      data on the concentrations of total and individual fungal types from five
      stations and 2 different years were analyzed and compared by statistical methods.
      The allergenicity of the prevalent airborne viable fungi was estimated by the
      skin-prick tests of >100 rural allergy patients using the antigenic fungal
      extracts from isolates collected with the Andersen sampler. The ranges of total
      fungal spore concentration were 82-2365 spores per cubic meter of air (spores/m3)
      in the first sampling year and 156-2022 spores/m3 in the second sampling year.
      The concentration ranges of viable fungi were 72-1796 colony-forming units per
      cubic meter of air (CFU/m3) in the first sampling year and 155-1256 CFU/m3 in the
      second sampling year. No statistically significant difference was observed
      between the total spore data of the 2 years, however, the data between five
      stations showed a significant difference (P<0.0001). No statistically significant
      difference existed between stations and years with respect to the concentration
      of viable fungi. When the data of individual allergenic fungal concentrations
      were compared between stations and years, no statistically significant difference
      was observed in all cases except for Aspergillus japonicus and Rhizopus
      nigricans, which showed significant difference in case of stations and years,
      respectively. The ratios between the total fungal spores collected by the Burkard
      sampler and the viable fungi collected by the Andersen sampler from all sampling
      stations ranged between 0.29 and 7.61. The antigenic extracts of eight prevalent
      viable airborne fungi (A. flavus, A. japonicus, A. fumigatus, Alternaria
      alternata, Cladosporium cladosporioides, Curvularia pallescens, Fusarium roseum,
      and R. nigricans) demonstrated >60% positive reactions in the skin prick test.
      These selected allergenic fungi collectively represented 31.7-63.2% of the total
      airborne viable fungi in different stations. The study concluded that: (i) a rich
      fungal airspora existed in the rural study area, (ii) to achieve representative
      information on the total airborne fungal spores of an area, the monitoring in
      multiple sampling stations is preferable over a single sampling station; for
      viable fungi, however, one station can be considered, (iii) the percentage of
      airborne fungal viability is higher in rural agricultural areas, and (iv)
      approximately 52% of the viable airborne fungi in the rural study area were
      allergenic.

PMID- 15142772
TI  - Polycyclic aromatic hydrocarbons inside and outside of apartments in an urban
      area.
AB  - In the context of environmental monitoring in Berlin polycyclic aromatic
      hydrocarbon (PAH) concentrations in air and household dust were measured inside
      123 residences (and simultaneously in a sub group in the air outside the
      windows). The aim of this study was to determine exposure to PAHs in the
      environment influencing by several factors, for instance, motor vehicle traffic
      in a populous urban area. Indoor air samplings were carried out in two periods
      (winter and spring/summer) in smokers and non-smokers apartments. Benzo(a)pyrene
      (BaP) median values were 0.65 ng m(-3) (winter) and 0.27 ng m(-3) (spring/summer)
      in smokers' apartments and 0.25 ng m(-3) (winter) and 0.09 ng m(-3)
      (spring/summer) in the apartments of non-smokers. The median BaP content in
      ambient air was 0.10 ng m(-3) (maximum: 1.1 ng/m(-3)) with an indoor-outdoor mean
      concentration ratio of 0.9 in non-smoker households and 5.4 in smoker apartments.
      In household dust we obtained median values of 0.3 mg kg(-1) (range: 0.1-1.4 mg
      kg(-1)). We found a significant relation between indoor and outdoor values.
      Approximately 75% of the variance of indoor air values was caused by the
      corresponding BaP concentrations in the air outside the apartment windows.
      Otherwise a significant correlation between indoor air and household dust values
      cannot be found. Therefore, according to our results, it is suggested that the
      indoor PAH concentration in non-smoker apartments could be attributed mainly to
      vehicular emissions.

PMID- 15142773
TI  - The effects of meteorological factors on atmospheric bioaerosol concentrations--a
      review.
AB  - Over land surfaces a quarter of the total airborne particulate may be made up of
      biological material in the form of pollen, fungal spores, bacteria, viruses, or
      fragments of plant and animal matter. Meteorological variables affect the initial
      release of this material and its dispersal once airborne. Temperature and water
      availability will affect the size of the source and will control the release of
      some actively released fungal spores. Inertly released material will become
      airborne when the drying of the surface reduces bonding forces, and when the
      material is disrupted by sufficiently strong air movement or by mechanical
      disturbance. The wind speed necessary to disrupt material is noted to be less on
      a plant surface than on the ground surface. Measurements of the concentrations of
      airborne material near dominant sources are reviewed for both area sources, and
      for point sources such as sewage and waste treatment works, agricultural
      practices, and diseased animals. The concentration of airborne material remote
      from sources is considered along with the effects of on and off shore winds and
      some examples of long distance transport of material. The vertical concentration
      of bacteria is noted to decline less rapidly than that of fungal spores. The
      short-term variation of pollen, fungal spore, and bacterial concentrations are
      also considered.

PMID- 15142774
TI  - Seasonal concentrations of cadmium and zinc in native pasture plants:
      consequences for grazing animals.
AB  - Aboveground concentrations of Cd and Zn in various grazing plants at three stages
      of the growing season are reported. The plants were collected at a natural
      habitat exposed to extensive atmospheric deposition of heavy metals from other
      parts of Europe. Concentrations of both metals varied considerably among species,
      also among morphologically similar species growing in the same soil. The two
      metals correlated in the material as a whole, but the concentration variations
      were most pronounced for Cd. There were also seasonal variations (generally a
      concentration reduction during spring). Transfer of metals from twigs to leaves
      seemed to differ between 'high' and 'low' metal accumulators. The inter-species
      and seasonal variations in plant metal concentrations complicate assessments of
      metal exposure to grazing animals through diet. By using diet information from a
      study conducted in an area similar to the present one, we roughly estimated a
      daily intake of 1-2 mg Cd for moose (Alces alces) in the autumn. Among the plant
      species investigated, Populus and Salix species were by far the most important Cd
      contributors. In areas where high Cd accumulators grow more widely, the daily Cd
      intake by moose could be as high as 7 mg or more.

PMID- 15142775
TI  - As(V) retention and As(III) simultaneous oxidation and removal on a MnO2-loaded
      polystyrene resin.
AB  - Based on KMnO4 oxidative capacity, a polystyrene matrix loaded with manganese
      dioxide was synthesized from an anionic commercial resin in chloride form. This
      medium, called R-MnO2, was tested for As(V) retention and for As(III)
      simultaneous oxidation and removal. Equilibrium was reached in 2 h and isotherms
      showed that R-MnO2 maximal capacities towards As(III) and As(V) are,
      respectively, 0.7 and 0.3 mmol/g. Various mechanisms were involved in As(III)
      retention: oxidation of H3AsO3(0) by MnO2(s) leading to the formation of HAsO4(2)
      and Mn2+, fixation of As(V) formed on the resin beads and precipitation of
      Mn3(AsO4)2 with Mn2+ released. Successive arsenic desorption and retention steps
      were performed and showed that the quantity desorbed was low compared to the
      quantity removed during the first stage of the process. A second removal step,
      carried out under the same conditions as the first one, proved that the matrix
      second-removal capacity was weak. This solid sorbent, although not reusable, can
      be considered in field application as arsenic retention is really strong.

PMID- 15142777
TI  - Sorption of ionizable organic compounds on HDTMA-modified loess soil.
AB  - A natural loess soil was modified using a cationic surfactant,
      hexadecyltrimethylammonium (HDTMA) bromide. Sorption of ionizable organic
      compounds (IOCs), 2,4-dichlorophenol (DCP), p-nitroaniline (NA) and benzoic acid
      (BA), on the modified soil was determined under different pH conditions. The
      objective of this study was to examine the sorptive characteristics of IOCs on
      HDTMA-modified loess soil as a function of pH in an attempt to establish the
      sorptive models and mechanisms for predicting the sorptive behaviors of IOCs on
      the HDTMA-modified loess soil. The sorption isotherms of DCP, NA and BA with the
      soil were obtained using the batch equilibration method. Results indicated that
      the sorption isotherms of IOCs, regardless of ionic or neutral forms, were non
      linear and obeyed to the Freundlich equation. A model describing the sorption of
      IOCs on the HDTMA-modified loess soil was derived from the experimental data. The
      model well predicted the sorption of DCP from individual sorption of both ionic
      and neutral species of the IOC. In binary solute systems, sorption of NA was
      reduced in the presence of DCP or BA, which indicated that DCP and BA had a
      competitive effect on the sorption of NA on the HDTMA-modified loess soil. The
      effect of DCP on the sorption of NA gradually increased with decreasing pH from
      10.8 to 6.7, suggesting a stronger effect of neutral DCP than that of the ionic
      species on the sorption of NA. Modification of loess soil may effectively
      immobilize ionizable organic contaminants in soil environment.

PMID- 15142776
TI  - Metal uptake by young trees from dredged brackish sediment: limitations and
      possibilities for phytoextraction and phytostabilisation.
AB  - Five tree species (Acer pseudoplatanus L., Alnus glutinosa L. Gaertn., Fraxinus
      excelsior L., Populus alba L. and Robinia pseudoacacia L.) were planted on a
      mound constructed of dredged sediment. The sediment originated from a brackish
      river mouth and was slightly polluted with heavy metals. This preliminary study
      evaluated the use of trees for site reclamation by means of phytoextraction of
      metals or phytostabilisation. Although the brackish nature of the sediment caused
      slight salt damage, overall survival of the planted trees was satisfactory.
      Robinia and white poplar had the highest growth rates. Ash, maple and alder had
      the highest survival rates (>90%) but showed stunted growth. Ash, alder, maple
      and Robinia contained normal concentrations of Cd, Cu, Pb and Zn in their
      foliage. As a consequence these species reduce the risk of metal dispersal and
      are therefore suitable species for phytostabilisation under the given conditions.
      White poplar accumulated high concentrations of Cd (8.0 mg kg(-1)) and Zn (465 mg
      kg(-1)) in its leaves and might therefore cause a risk of Cd and Zn input into
      the ecosystem because of autumn litter fall. This species is thus unsuitable for
      phytostabilisation. Despite elevated metal concentrations in the leaves,
      phytoextraction of heavy metals from the soil by harvesting stem and/or leaf
      biomass of white poplar would not be a realistic option because it will require
      an excessive amount of time to be effective.

PMID- 15142778
TI  - Mobility of the growth promoters trenbolone and melengestrol acetate in
      agricultural soil: column studies.
AB  - There is growing concern about environmentally released man-made chemicals
      suspected to be responsible for a number of adverse effects on endocrine function
      in wildlife species and possibly also in humans. Sex hormones are of particular
      interest due to their regulatory role in developmental processes such as sexual
      differentiation. Endogenous hormones of human or animal origin as well as
      exogenous sex steroids used for contraception or as anabolics for farm animals
      are excreted and reach the environment. We investigated the transport of the
      synthetic growth promoters trenbolone (TbOH) and melengestrol acetate (MGA) in
      agricultural soil by means of column experiments with aggregated soil materials
      (Ap and Bt horizons of a Luvisol). Column effluent concentrations and depth
      profiles of TbOH and MGA were determined with sensitive enzyme immunoassay
      systems and HPLC (RP-18), respectively. All procedures were confirmed by liquid
      chromatography-mass spectrometry. Small amounts of TbOH and MGA passed the
      columns very quickly. However, both hormones exhibited a high affinity to the
      organic matter of both horizons leading to a high retardation within the upper
      layers of the soil columns. Although we cannot deduce whether hormones of animal
      origin reach the ground water under field conditions, our model experiments show
      that their transition can be presumed.

PMID- 15142780
TI  - Behaviour of uranium in hydroxyapatite-bearing permeable reactive barriers:
      investigation using 237U as a radioindicator.
AB  - This study was undertaken to investigate the long-term performance of
      hydroxyapatite (HAP) as reactive material for the removal of uranium in passive
      groundwater remediation systems. 237U used as a radioindicator enabled tracking
      the movement of the contamination front through a test column without taking
      samples or dismantling the apparatus. The stoichiometric ratio between uranium
      and HAP was found to be 1:(487 +/- 19). Uranium removal by HAP is of pseudo first
      order kinetics and the rate constant was measured to be (1.1 +/- 0.1) x 10(-3) s(
      1). HAP can sorb more than 2900 mg/kg uranium. Possible reaction pathways of
      uranium and HAP are discussed. The data obtained enable the calculation of ideal
      lifetime for permeable reactive barriers (PRB) using HAP for uranium removal
      neglecting hydrological factors that may impair the function of PRBs.

PMID- 15142779
TI  - Influence of organic matter on the uptake of cadmium, zinc, copper and iron by
      sorghum plants.
AB  - This article describes an experiment, carried out under controlled environment
      conditions, to investigate the effects of a fulvic acid fraction of soil organic
      matter on growth, cadmium (Cd) uptake and redistribution by sorghum. In addition
      the uptake of copper (Cu), zinc (Zn) and iron (Fe) was also determined. Sorghum
      was grown in nutrient solutions with 0, 0.1, 1 and 10 mg Cd dm(-3), in the
      absence and presence of organic matter (32 mg C dm(-3)), for various periods up
      to 20 days. A decrease in sorghum biomass due to Cd toxicity was observed at 10
      mg Cd dm(-3), but for concentrations of 0.1 and 1 mg Cd dm(-3) the biomass was
      increased compared with control, without visual toxicity symptoms. The presence
      of organic matter (OM) further increased biomass production. Cadmium was mainly
      retained in sorghum roots, as usually found in tolerant plants, but Cd
      accumulation in sorghum was greater than in other Gramineae, or even more
      tolerant plants such as lettuce. The presence of OM decreased the bioavailability
      of Cd that was partially retained in solution by the OM ligands. However, OM
      promoted the translocation of Cd to shoots, an effect that may pose a risk to
      public health because plant-animal transfer of Cd could be enhanced. The presence
      of OM decreased the uptake of Cu, Zn and Fe. The presence (vs. absence) of 0.1 mg
      Cd dm(-3) enhanced the uptake of Fe, both in the absence and presence of OM.

PMID- 15142781
TI  - Temporal variations of mineral character of acid-producing pyritic coastal
      sediments, Southeast Queensland, Australia.
AB  - The lower Pimpama River catchment possesses many features of morphology, geology
      and landuse, typical for Southeast Queensland. Pimpama River and its main
      tributary Hotham Creek meander over a coastal plain which developed during the
      last several thousand years as a result of sea level fluctuations and changing
      fluvial and estuarine regimes which provided ideal conditions for the formation
      of sedimentary pyrite. A complex mixture of natural and human factors triggers
      and controls the oxidation and hydrolysis of this pyrite. The consequent
      production of sulfuric acid and leaching of metals from the pyrite-rich sediments
      represent main environmental issues of this coastal setting. This study aimed to
      determine the lithological character of the coastal unconsolidated sediments, and
      identify changes produced by acidity over a long period of time in a natural
      system and over a short period of time in a laboratory system. The mineral
      composition of the estuarine sediments of the coastal plain reflects the
      lithology of their source, the geological basement, and also the enhanced
      weathering rate due to acid production. The primary minerals present in the
      sediments consist of quartz and feldspars (primarily albite, K-feldspars to a
      lesser extent and minor anorthite) the product of physical weathering of bedrock
      material, mainly sandstone. Kaolinite is the dominant clay mineral and represents
      the product of intense leaching of feldspars promoted by acid conditions.
      Kaolinite is fairly ordered in structure in fresh and weathered bedrock and it
      becomes disordered in the estuarine sediments. Illite is mainly present in
      bedrock-related samples and the highest amounts are associated with muscovite. In
      the tidal sediments, illite is present to a lesser extent and is not found in the
      lower estuary. The distribution of mixed layers of smectite-illite is highly
      variable and their deposition is mainly controlled by the hydrodynamic conditions
      of the environment. Only low energy tidal settings favour the deposition of
      smectites. Pyrite is present at many sites and is always accompanied by oxidation
      products such as jarosite and gypsum. The laboratory experiment showed that in
      the short-term, changes induced by acid production mainly involved the: (1)
      decomposition of oxidation products such as gypsum and jarosite, (2) weathering
      of feldspars (mainly plagioclase), and (3) increased amount of kaolinite and
      possible increased structural disorder. These observations are of significance
      when considering wetlands as a method of remediating acid-producing areas by re
      establishment of reducing conditions. Jarosite is quite widespread and can
      represent a source of acid over a short period of time in water-saturated,
      partially oxidized pyrite-rich sediments. The initial several months of a wetland
      establishment may, however, be dominated by secondary acid production and metal
      leaching from preexisting oxidation products like jarosite and natrojarosite.

PMID- 15142782
TI  - Moisture distribution in activated sludges: a review.
AB  - The dewatering of residual sludges is a current problem due to the huge
      production of this waste. Activated sludges are generally hard to dewater, and
      the design and the control of the separation operations are often quite
      difficult. In order to better understand this problem, pertinent indices are
      needed. The knowledge of how water is distributed within activated sludge is an
      interesting approach. Current literature dealing with this topic is, however,
      relatively difficult to apply. This work presents a review of the problem of
      moisture distribution classification and measurement within activated sludge. The
      main techniques used for this analysis are compared and discussed in detail. The
      estimation of the water binding energy is also extremely commented upon. Finally,
      the paper discusses the utility of this type of analysis to examine the
      conditioning and dewatering of activated sludge.

PMID- 15142783
TI  - Predicting the rate and extent of cadmium and copper desorption from soils in the
      presence of bacterial extracellular polymer.
AB  - The movement of cationic transition metals through the subsurface is strongly
      retarded by sorption to the porous media. However, dissolved organic ligands can
      compete with soil surfaces by providing binding sites for metals in solution. An
      extracellular polymer produced by a bacterium isolated from soil was used in this
      study to observe and model the influence of a naturally occurring ligand on the
      release of adsorbed metals from two test soils. Experimental results show that
      the presence of dissolved extracellular polymer enhanced the rate and extent of
      desorptive release of soil-bound cadmium and copper. A kinetic model that uses a
      gamma distribution of rate constants to account for the physical and chemical
      heterogeneity of the soil matrix was employed to describe the release of cadmium
      and copper in batch experiments. Model parameters describing soil, metal and
      extracellular polymer interactions were obtained through separate experiments.
      With these parameters the model successfully predicted the influence of dissolved
      polymer on the rate and extent of release of cadmium and copper from soil in
      independent batch experiments. These results suggest that the presence of natural
      metal-binding ligands such as bacterial extracellular polymers can act to
      increase the driving force for desorption by lowering the aqueous concentration
      of free unbound metals in solution.

PMID- 15142784
TI  - A pilot study of constructed wetlands using duckweed (Lemna gibba L.) for
      treatment of domestic primary effluent in Israel.
AB  - Constructed wetlands are well known as highly efficient system to treat
      wastewater from different sources. This treatment system is cost-effective for
      reuse in desert areas. A continuous flow, free water surface (FWS) pilot wetland
      using the duckweed plant Lemna gibba L. was constructed at the Blaustein
      Institute for Desert Research in Kiryat Sde Boker of the Negev, Israel, and
      operated on domestic primary effluents. Water quality and system efficiency were
      observed during the experiment for reuse purposes. Results indicated that,
      hydraulic residence time averaged 4.26+/-0.61d, average influent flow rate was
      0.234+/-0.027m(3)/d and hydraulic load 0.22+/-0.03m/d. Hydraulic efficiency in
      the system was high and allowed good settling conditions. Suspended solids and
      organic matter removals were the highest and effluent concentrations were 13.1+/
      9.7 and 40.3+/-11.9mg/l for TSS and total BOD(5), respectively. Nitrogen removal
      was lower (10-20%) but slightly increased with higher nitrogen loads. Therefore,
      nitrogen content in the plants was high (4.3+/-0.5%/kg dry plant). Phosphorus
      removal was negligible. High removal for fecal coliform (approximately 95%) and
      effluent turbidity (> 50%) were also observed.

PMID- 15142785
TI  - Effect of cavitation on chemical disinfection efficiency.
AB  - This study brings out the potential efficacy of hybrid techniques for water
      disinfection. The techniques studied include hydrodynamic cavitation, acoustic
      cavitation and treatment with chemicals like hydrogen peroxide and ozone. The
      hybrid techniques which combine hydrodynamic cavitation, acoustic cavitation and
      hydrogen peroxide appear to be an attractive alternative to any one technique on
      its own for the reduction in the heterotropic plate count bacteria as well as
      indicator microorganisms like the total coliforms, fecal coliforms and fecal
      streptococci.

PMID- 15142787
TI  - Application of multi-way models to the time-resolved fluorescence of polycyclic
      aromatic hydrocarbons mixtures in water.
AB  - The time-resolved laser-induced fluorescence of a series of polycyclic aromatic
      compounds (PAHs) and mixtures of these latter in aqueous solution was measured by
      means of an apparatus equipped with optical fibers, which allows their real time
      in situ monitoring. The potential of such spectroscopic technique, yielding 4-way
      fluorescence data arrays, together with the application of multi-way models to
      the matricized data, was tested for the resolution of complex aqueous mixtures
      containing low concentrations of PAHs, as typical fluorescent pollutants in
      aquatic systems. PARAllel FACtors analysis was employed for the qualitative
      resolution of PAHs mixtures and for calculating the fluorescence lifetimes of
      single PAHs; n-way partial least squares analysis was applied for evaluating the
      concentration of the single PAHs in the aqueous mixtures.

PMID- 15142786
TI  - Performance of a fungal biofilter treating gas-phase solvent mixtures during
      intermittent loading.
AB  - Biological treatment processes used to remove and degrade volatile organic
      compounds (VOCs) from contaminated gases emitted by industrial operations or
      waste treatment processes are almost always subjected to transient loading
      conditions because of the inherently unsteady-state nature of contaminant
      generating processes. In the study presented here, a laboratory-scale biofilter
      populated by a mixed culture of fungi was used to study the transient response to
      various periods of no contaminant loading in a system treating a model waste gas
      stream containing a mixture of commonly used solvents. The biofilter, packed with
      cubed polyurethane foam media and operated with an empty bed residence time of
      15s, was supplied with a four-component mixture of n-butyl acetate, methyl ethyl
      ketone, methyl propyl ketone, and toluene at target influent concentrations of
      124, 50.5, 174, and 44.6 mg/m(3), respectively. This corresponds to a total VOC
      loading rate of 94.3g/(m(3)h). Biofilter performance was evaluated over a 94-day
      period for three loading conditions intended to simulate processes generating
      contaminated gases only during daytime operation, daytime operation with weekend
      shutdown periods, and with long term (9-day) shutdown. Results indicate that
      fungal biofilters can be an effective alternative to conventional abatement
      technologies for treating solvent contaminated off-gases even under discontinuous
      loading conditions.

PMID- 15142788
TI  - Atrazine degradation in anaerobic environment by a mixed microbial consortium.
AB  - Atrazine degradation by anaerobic mixed culture microorganism in co-metabolic
      process and in absence of external carbon and nitrogen source was studied at
      influent atrazine concentration range of 0.5-15 mg/l. Wastewater of desired
      characteristic was prepared by the addition of various constituents in distilled
      water spiked with atrazine. In co-metabolic process, dextrose of various
      concentrations (150-2000 mg/l) was supplied as external carbon source. The
      reactors were operated in sequential batch mode in which 20% of treated effluent
      was replaced by the same amount of fresh wastewater everyday, thus maintaining a
      hydraulic retention time (HRT) equal to 5 days. In co-metabolic process, 40-50%
      of influent atrazine degradation was observed. First-order atrazine degradation
      rate (expressed in day(-1)) was better in co-metabolic process (5.5 x 10(-4))
      than in absence of external carbon source (2.5 x 10(-5)) or carbon and nitrogen
      source (1.67 x 10(-5)). In presence of 2000 mg/l of dextrose, atrazine
      degradation was between 8% and 15% only. Maximum atrazine degradation was
      observed from wastewater containing 300 mg/l of dextrose and 5mg/l of atrazine.
      Influent atrazine concentration did not have much effect on the methanogenic
      bacteria which was clear from methane gas production and specific methanogenic
      activity (SMA).

PMID- 15142789
TI  - Kinetic decomposition of ozone and para-chlorobenzoic acid (pCBA) during
      catalytic ozonation.
AB  - The decomposition of ozone and para-chlorobezoic acid (pCBA) using ozone and
      ozone/goethite were investigated under various conditions to define the
      characteristics of ozonation and catalytic ozonation. A continuous analysis of
      the kinetics of the reaction between ozone and pCBA was established, and the
      decay rate of ozone and pCBA with/without goethite was determined. The decay rate
      of ozone in the presence of goethite was much higher than in the absence of
      goethite and was strongly pH dependent due to the reactivities of ozone with the
      three surface species ( identical with FeOH(2)(+), identical with FeOH, identical
      with FeO(-)) of goethite. The removal pattern of ionized pCBA at different pHs
      agreed well with the instantaneous ozone demand. The removal rate of pCBA and
      instantaneous ozone demand with/without t-butanol at different pHs were compared
      to elucidate the reaction mechanisms associated with the three reaction sites:
      (i) on the surface of the catalyst, (ii) at the catalyst-solution interface, and
      (iii) in the bulk solution.

PMID- 15142790
TI  - Accelerated start-up and enhanced granulation in upflow anaerobic sludge blanket
      reactors.
AB  - In the present study, the effects of a cationic polymer on reactor start-up and
      granule development were evaluated. A control reactor R1 was operated without
      adding polymer, while the other five reactors designated R2, R3, R4, R5 and R6
      were operated with different polymer concentrations of 20, 40, 80, 160 and 320
      mg/L, respectively. Experimental results demonstrated that adding the polymer at
      a concentration of 80 mg/L markedly accelerated the start-up time. The time
      required to reach stable treatment at an organic loading rate (OLR) of 4 g
      COD/L.d was reduced by approximately 50% in R4 as compared with the control
      reactor. The same reactor with 80 mg/L polymer was able to achieve an OLR of 12 g
      COD/L.d after 59 days of operation, while R1, R2, R3, R5 and R6 achieved the same
      loading rate at much longer period of 104, 80, 69, 63 and 69 days, respectively.
      Comparing with the control reactor, the start-up time of R4 was shortened
      markedly by about 43% at this OLR, while other reactors also recorded varying
      degree of shortening. Monitoring on granule development showed that the granule
      formation was accelerated by 30% from the use of the appropriate dosage of
      polymer. Subsequent granules characterization indicated that the granules
      developed in R4 with 80 mg/L polymer exhibited the best settleability, strength
      and methanogenic activity at all OLRs. The organic loading capacities of reactors
      were also increased by the polymer addition. The maximum organic loading of the
      control reactor was 24 g COD/L.d, while the polymer-assisted reactor added with
      80 mg/L polymer attained a markedly increased organic loading of 40 g COD/L.d.
      The laboratory results obtained demonstrated that adding the cationic polymer
      could result in shortening of start-up time and enhancement of granulation, which
      in turn lead to improvement in organics removal efficiency and loading capacity
      of the UASB system.

PMID- 15142791
TI  - Phototransformation of selected organophosphorus pesticides in dilute aqueous
      solutions.
AB  - The photochemical transformation of four selected organophosphorus pesticides
      (OPs) has been studied in water. Because of their extensive use, disulfoton,
      isofenfos, isazofos and profenofos were chosen for this study. A solid phase
      extraction method has been developed to allow low-concentration experiments.
      Photolysis experiments have been performed both in purified water and in Capot
      river water (natural water from Martinique) using either monochromatic light at
      253.7 nm (purified water) or polychromatic light greater than 285 nm (purified
      and Capot river waters). Kinetic investigations coupled with analytical studies
      (identification of degradation products) were performed for the four pesticides.
      Upon monochromatic irradiation, quantum yields of OP photolysis have been
      evaluated and in polychromatic irradiation experiments, apparent first-order
      kinetic constants have been determined. The reactivity is similar in purified and
      natural water, but differences are observed for each pesticide according to the
      role that natural organic matter (NOM) plays: filter effect of the light or
      photosensitizer. For each organophosphorus pesticide, experiments have been
      performed to identify the photodegradation products. Some photoproduct structures
      will be proposed according to mass spectral informations.

PMID- 15142792
TI  - Removal of chlorophenols from groundwater by chitosan sorption.
AB  - The equilibrium and kinetics of chlorophenol (CP) sorption by chitosan, poly D
      glucosamine, were studied under simulated groundwater conditions. Lower
      temperature, from 25 degrees C to 15 degrees C and then 5 degrees C, markedly
      decreased the adsorption rates by a factor of 30-53% and 7-22%. Comparison
      between two types of chitosan, flakes and highly swollen beads, demonstrated that
      the maximum pentachlorophenol (PCP) uptake capacities in Langmuir and Freundlich
      models depend on the specific surface area of the particle. Low temperature (5
      degrees C) significantly increased the PCP uptake capacity in comparison to
      higher temperatures (15 degrees C and 25 degrees C). PCP uptake capacity was
      halved at pH levels higher than 6.5, and NaCl concentrations greater than 1%
      blocked PCP sorption almost completely. Of five kinds of chlorophenols, i.e.
      2,4,6-trichlorophenol (2,4,6-TCP), 3,4-dichlorophenol (3,4-DCP), 2,3
      dichlorophenol (2,3-DCP), 2,6-dichlorophenol (2,6-DCP), 3-monochlorophenol (3
      MCP), TCP had the maximum sorption efficiency on flake-type chitosan, followed by
      DCPs, and finally MCP (the three kinds of DCP, with the same elemental
      compositions, achieved similar sorption performances).

PMID- 15142793
TI  - Biodegradation of natural and synthetic estrogens by nitrifying activated sludge
      and ammonia-oxidizing bacterium Nitrosomonas europaea.
AB  - This report describes the uses of nitrifying activated sludge (NAS) and ammonia
      oxidizing bacterium Nitrosomonas europaea to significantly degrade estrone (E1),
      17beta-estradiol (E2), estriol (E3), and 17alpha-ethynylestradiol (EE2). Using
      NAS, the degradation of estrogens obeyed first-order reaction kinetics with
      degradation rate constants of 0.056 h(-1) for E1, 1.3 h(-1) for E2, 0.030 h(-1)
      for E3, and 0.035 h(-1) for EE2, indicating that E2 was most easily degraded.
      Then, we confirmed that E2 was degraded via E1 by NAS. With/without the ammonia
      oxidation inhibitor, it was observed that ammonia-oxidizing bacteria in
      conjunction with other microorganisms in NAS degraded estrogens. Using N.
      europaea, the degradation of estrogens reasonably obeyed zero-order reaction
      kinetics, and no remarkable difference is present among the four estrogens
      degradation rates and it was found that E1 was not detected during E2 degradation
      period. We suggested that E2 was degraded to E1 in NAS could be caused by other
      heterotrophic bacteria, not by ammonia-oxidizing bacteria.

PMID- 15142794
TI  - Electrochemical removal of bisphenol A based on the anodic polymerization using a
      column type carbon fiber electrode.
AB  - Electrochemical removal based on the polymerization of organic pollutants on an
      anode surface was performed on bisphenol A (BPA) and its derivatives, bisphenol S
      (BPS) and diphenolic acid (DPA). It was confirmed by voltammetric techniques that
      the electrochemical oxidation of these compounds leads to the formation of a
      polymeric film on a carbon electrode surface. The electrochemical removals of
      BPA, BPS and DPA based on the anodic polymerization were attempted in the batch
      type cell. A carbon fiber (CF) was used as an anode with a very large surface
      area. The high removal efficiency for BPA, BPS, and DPA was obtained by applying
      a potential at 0.75-, 1.0-, and 0.8-V, respectively. The removal efficiency for
      BPA does not decrease in the presence of 10ppm humic acid. The electropolymerized
      BPA film formed on the CF surface was characterized by FT-IR and UV/vis. The
      continuous treatment of BPA was achieved by using the flow system with a column
      type of CF electrode. The applicability of this method for removal of BPA from
      aqueous solution was tested at several different conditions, i.e., flow rate of
      solution and concentration of electrolyte and BPA. This system can be applied for
      removal of a low concentration BPA even from low electrolyte concentrations of
      aqueous solution.

PMID- 15142795
TI  - Plasmachemical degradation of azo dyes by humid air plasma: Yellow Supranol 4 GL,
      Scarlet Red Nylosan F3 GL and industrial waste.
AB  - A recent non-thermal plasma technique (i.e., a gliding arc discharge which
      generates reactive species at atmospheric pressure) is tested for pollution
      abatement of dyes dispersed in synthetic solutions and industrial effluents.
      Yellow Supranol 4 GL (YS) and Scarlet Red Nylosan F3 GL (SRN) are toxic synthetic
      dyes widely used in the Algerian textile industry and frequently present in
      liquid wastes of manufacture plants. Classical removal treatment processes are
      not efficient enough, so that the presence of dyes in liquid effluents may cause
      serious environmental problems, in connection with reusing waste waters for
      irrigation. The degradation processes achieved by the oxidising species formed in
      the plasma are followed by UV/VIS spectroscopy and by chemical oxygen demand
      measurements. They are almost complete (i.e., 92.5% for YS and 90% for dilute
      SRN) and rapidly follow pseudo-first-order laws, with overall estimated rate
      constants 3 x 10(-4) and 4 x 10(-4)s-1 for YS and SRN, respectively. The
      degradation rate constant for the industrial mixture (i.e., k = 1.45 x 10(-3)s-1)
      is a mean value for two consecutive steps (210(-3) and 6 x 10(-5)s-1) measured at
      the absorption peaks of the major constituent dyes, YS and SRN.

PMID- 15142796
TI  - Anaerobic sewage treatment in a one-stage UASB reactor and a combined UASB
      Digester system.
AB  - The treatment of sewage at 15 degrees C was investigated in a one-stage upflow
      anaerobic sludge blanket (UASB) reactor and a UASB-Digester system. The latter
      consists of a UASB reactor complemented with a digester for mutual sewage
      treatment and sludge stabilisation. The UASB reactor was operated at a hydraulic
      retention time of 6h and a controlled temperature of 15 degrees C, the average
      sewage temperature during wintertime of some Middle East countries. The digester
      was operated at 35 degrees C. The UASB-Digester system provided significantly
      (significance level 5%) higher COD removal efficiencies than the one-stage UASB
      reactor. The achieved removal efficiencies in the UASB-Digester system and the
      one-stage UASB reactor for total, suspended, colloidal and dissolved COD were
      66%, 87%, 44% and 30%, and 44%, 73%, 3% and 5% for both systems, respectively.
      The stability values of the wasted sludge from the one-stage UASB reactor and the
      UASB-Digester system were, respectively, 0.47 and 0.36g CH(4)-COD/g COD.
      Therefore, the anaerobic sewage treatment at low temperature in a UASB-Digester
      system is promising.

PMID- 15142798
TI  - Recovery of Escherichia coli in fresh water fish, Jenynsia multidentata and
      Bryconamericus iheringi.
AB  - Escherichia coli concentration was determined in digestive tract and muscle of
      Jenynsia multidentata and Bryconamericus iheringi through bioassays. Field
      experiments were also conducted with J. multidentata collected in the Suquia
      River, Cordoba, Argentina. E. coli was quantified by the most probable number,
      using lauryl sulphate tryptose broth with 4-methylumbelliferyl-beta-D
      glucuronide. For bioassays, E. coli concentrations 10(2), 10(3), 10(4), 10(5),
      10(6)CFU/ml were introduced in aquarium water. E. coli was recovered from the
      digestive tracts of J. multidentata and B. iheringi in all the concentrations
      assayed. Bacterial critical load in water for the recovery of bacteria from
      muscle, was 10(3)CFU/ml for both species. The regression analysis between E. coli
      loads in water and those found in digestive tract and muscle showed a positive
      linear relationship for J. multidentata and B. iheringi. The same relation was
      observed between the concentration of bacteria in digestive tract and muscle in
      both species. In field experiments, E. coli was recovered from digestive tract
      and muscle of J. multidentata. The presence of E. coli in the studied fish
      suggests that they can carry bacteria to non-polluted waters. However, further
      studies are necessary to evaluate its significance for public and environmental
      health.

PMID- 15142797
TI  - Removal and transformation of recalcitrant organic matter from stabilized saline
      landfill leachates by coagulation-ozonation coupling processes.
AB  - The Bordo Poniente sanitary landfill in Mexico City currently receives 11,500
      ton/day of solid wastes. The landfill has been in operation since 1985, in what
      was formerly Texcoco Lake, now a dried-up lakebed. The physico-chemical
      characteristics of the leachate generated by this particular landfill are altered
      by the incorporation of freatic saline water present in the area. This paper
      reports the results from a study evaluating coagulation and ozonation as
      alternative processes for removing and transforming recalcitrant organic matter
      from stabilized saline landfill leachate. Coagulation with ferric sulfate was
      found to remove up to 67% of COD and 96% of leachate color. The remaining 33% COD
      was removed with ozone. Recalcitrant organic matter removal by ozonation is
      limited by the reaction kinetic due mainly to ozone's low reactivity with the
      organic compounds present in the leachates (amines, amides, alcohols, aliphatic
      compounds, and carboxylic acids). However, ozone contributes greatly to changing
      the recalcitrant characteristics of organic matter. Leachate biodegradability was
      found to be significantly enhanced through ozonation: BOD(5) values reach 265%,
      and the BOD(5)/COD ratio increases from 0.003 to 0.015. Infrared analysis of
      ozonated leachates shows that the main by-products of recalcitrant organic matter
      ozonation are an increase in the hydroxyl and carboxylic groups, and the presence
      of aldehydes groups.

PMID- 15142800
TI  - Effects of chloride and sulfate on the rate of oxidation of ferrous ion by H2O2.
AB  - The rates of oxidation of Fe(II) by H(2)O(2) in the presence of sodium
      perchlorate, sodium nitrate, sodium chloride and sodium sulfate salts (0-1M) have
      been compared in the study. Experiments were carried out in a batch reactor, in
      the dark, at pH <3, 25+/-0.5 degrees C and at controlled ionic strength (< or
      =1M). The experimental results showed that the rates of oxidation of Fe(II) in
      the presence of chloride, nitrate and perchlorate were identical. In the presence
      of sulfate, the rate of oxidation of Fe(II) was faster and depended on the pH and
      the concentration of sulfate. The pseudo second-order rate constants for the
      reaction of H(2)O(2) with Fe(2+), FeCl(+) and FeSO(4) were determined as 55+/-1,
      55+/-1 and 78+/-3 M(-1) s(-1), respectively.

PMID- 15142799
TI  - Formation of haloacetic acids during monochloramination.
AB  - Factors that affect the formation of haloacetic acids (HAAs) during
      monochloramination, such as monochloramine application techniques, the initial
      chlorine (Cl) to ammonia-N (N) ratios, the bromide concentrations, and the
      wastewater quality, were studied. Aqueous humic acid solutions and undisinfected
      wastewater effluent samples obtained from two Hong Kong Sewage Treatment Works
      (STWs) were monochloraminated under various conditions. HAA formation was
      strongly affected by the monochloramine application techniques. The formation of
      trichloroacetic acid (TCAA) and total HAAs was reduced by adding preformed
      monochloramine. A higher initial Cl:N ratio indicated a higher chlorine demand
      and consequently led to higher HAA yields. Increasing the bromide concentration
      shifted HAAs from chlorinated species to brominated species and increased the
      yields of total HAAs, concurrent with decreases in the yields of dichloroacetic
      acid (DCAA) and TCAA but with increases in those of the other HAAs measured.
      Variations in the patterns of HAA formation were observed in monochloraminated
      wastewater effluent samples. The variations cannot be simply explained by the
      chlorine chemistry involving ammonia and/or bromide but are likely attributable
      to the combining effects of the water quality and the characteristics of the
      organics in the wastewater.

PMID- 15142801
TI  - Effect of chlorine on filamentous microorganisms present in activated sludge as
      evaluated by respirometry and INT-dehydrogenase activity.
AB  - Activated sludge technology is more used than any other for biological treatment
      of wastewater. However, filamentous bulking is a very common problem in activated
      sludge plants, chlorine being the chemical agent normally used to control it. In
      this work the effect of chlorine on microorganisms present in activated sludge
      flocs was assessed by a respirometric technique (oxygen uptake rate, OUR) and by
      the INT-dehydrogenase activity test (DHA) measured by two techniques:
      spectrophotometry (DHA(a)) and image analysis (DHA(i)). Both DHA tests were
      optimized and correlated with the respirometric technique (OUR) using pure
      cultures of a filamentous microorganism (Sphaerotilus natans) under chlorine
      inhibition. Using these correlations the tested methods were applied to determine
      the action of chlorine on respiratory activity in activated sludge. The OUR and
      the DHA(a) quantifies the action of chlorine on the total respiratory activity
      (RA) of flocs (filamentous and floc-forming bacteria); in contrast, the DHA(i)
      test evaluates specific action of chlorine on the RA of filamentous
      microorganisms. In activated sludge flocs containing filamentous microorganisms,
      a chlorine dose of 4.75 mgCl(2) (gVSS)(-1) with a contact time of 20 min reduced
      about 80% of the RA of filamentous bacteria while affecting only 50-60% of the
      total RA of flocs. Besides, a chlorine dose of 7.9 mgCl(2) (gVSS)(-1) produced
      the total respiratory inactivation of filamentous microorganisms after 10 min
      contact, however, with this dose the total RA of activated sludge flocs was
      reduced only about 45-65%; controlling filamentous bulking without affecting too
      much floc-forming bacteria. At the tested chlorine concentrations the inhibition
      of filamentous microorganisms was higher than in the whole activated sludge.
      Although floc-forming microorganisms were demonstrated to be more susceptible to
      chlorine than filamentous in pure cultures, results obtained in the present work
      confirmed that it is the location of the filamentous microorganisms in the flocs
      and the presence of extracellular polymer substances which largely determines
      their higher susceptibility to chlorine; consequently this feature plays a
      critical role in bulking control.

PMID- 15142802
TI  - Temperature effect on aerobic biodegradation of feces using sawdust as a matrix.
AB  - Temperature is one of the most important factors affecting microbial growth and
      biological reactions. In this study, the effect of temperature on aerobic
      biodegradation of feces is described through the comparison and analysis of
      experimental oxygen utilization rates (OUR) profiles obtained from batch tests
      conducted at several temperatures covering mainly mesophilic and thermophilic
      ranges. Additionally, the temperature effect was incorporated into the bio
      kinetic model introduced by Lopez Zavala et al. (Water Res 38(5) (2004) 1327) and
      simulation of experimental OUR profiles was conducted. Results show that
      mesophilic and thermophilic microorganisms behaved differently to temperature;
      additionally, results suggest that the optimum temperature from the viewpoint of
      feces biodegradability is within the thermophilic range, nearly 60 degrees C. The
      enzymatic activity of microorganisms at 70 degrees C was remarkably diminished.
      For better predictions in the mesophilic range, two fractions of slowly
      biodegradable organic matter were identified, easily hydrolyzable organic matter
      (X(Se)) and slowly hydrolyzable organic matter (X(Ss)).

PMID- 15142803
TI  - Effect of acid speciation on solid waste liquefaction in an anaerobic acid
      digester.
AB  - Laboratory scale experiments were carried out to evaluate and determine the
      suitable working conditions for the enhancement of volatile fatty acids (VFAs)
      production with the stabilization of solid pineapple waste (peel) simultaneously
      when operating two-phase anaerobic digestion. It was found that acid production,
      enhanced when the digester was operated at neutral pH. VFAs, could be obtained at
      about 50 g/kg-waste within 14 days when operating at pH 6.5-7.5 compared to 33
      g/kg-waste for digester operated at pH 5.0-6.0 for 32 days. The total volatile
      solid reduction of 42-48% was obtained with a 51-57% volume reduction at neutral
      pH. The effect of undissociated acids on the activity of acetogenic bacteria was
      also studied. The inhibitory level of undissociated acids for acidogenesis was
      found to be about 2300, 650, and 120 mg/L at pH 5, 6, and 7, respectively. The
      results revealed that at low pH, undissociated acids are inhibitory. It was found
      that for efficient operation of two-phase anaerobic digestion, both VFAs
      concentration and pH should be controlled.

PMID- 15142804
TI  - Removal of trivalent and hexavalent chromium with aminated polyacrylonitrile
      fibers: performance and mechanisms.
AB  - Aminated polyacrylonitrile fibers (APANFs) were prepared and used as an adsorbent
      in a series of batch adsorption experiments for the removal of Cr(III) and Cr(VI)
      species from aqueous solutions of different pH values. The results show that
      significant amounts of Cr(III) or Cr(VI) species can be adsorbed by the APANFs,
      although the adsorption performances was greatly dependent upon the solution pH
      values. In general, the amounts of adsorption for Cr(III) species increased
      whereas that for Cr(VI) decreased with the increase of the solution pH values,
      which suggests that different adsorption mechanisms dominated the removal of
      Cr(III) or Cr(VI) species on the APANFs. X-ray photoelectron spectroscopy and
      Fourier transform infrared spectroscopy revealed that the adsorption of Cr(III)
      species on the APANFs was largely attributed to the formation of surface
      complexes between the nitrogen atoms on the APANFs and the Cr(III) species
      adsorbed, but the adsorption of Cr(VI) species on the APANFs was more likely
      effected through the formation of hydrogen bonds at high solution pH values or
      through both electrostatic attraction and surface complexation at low solution pH
      values. It was found that the Cr(VI)-adsorbed APANFs can be effectively
      regenerated in a basic solution and be reused almost without any loss of the
      adsorption capacity, while the Cr(III)-adsorbed APANFs needed to be regenerated
      in an acidic solution and the regeneration appeared to be less effective.

PMID- 15142805
TI  - Changes in phosphorus removing performance and bacterial community structure in
      an enhanced biological phosphorus removal reactor.
AB  - A lab-scale-enhanced biological phosphorus removal (EBPR) reactor was operated
      for 204 days to investigate the correlation between phosphorus removing
      performance and bacterial community structure. The phosphorus removing
      performance was good from day 1 to 92 and from day 172 to 204. However, the
      removal activity was in a deteriorated state from day 93 to 171. From day 69 (2
      weeks before the beginning of the deterioration) to 118 (2 weeks after the
      beginning of the deterioration), sludge P content decreased. The amounts of
      ubiquinone-8 and menaquinone-8 (H(4)) decreased during this period while the
      amount of ubiquinone-10 increased. The comparison of these changes and the
      general attribution of each quinone to the bacterial phylogenetic groups
      suggested that beta proteobacteria and Actinobacteria contributed to EBPR
      positively, and that alpha proteobacteria were related to this EBPR
      deterioration. Glycogen accumulating organisms (GAOs) are considered to
      detrimentally affect EBPR ability by outcompeting the phosphorus accumulating
      organisms by using aerobically synthesized glycogen as the energy source to
      assimilate organic substrates anaerobically to form polyhydroxyalkanoates.
      However, in this research, there was nearly no substrate uptake during the
      anaerobic period at the middle of the deteriorated performance period. This
      suggests that the deterioration observed in this research does not agree with the
      GAOs inhibition model. In this research, the excess P release at the anaerobic
      period was concluded to cause the deterioration.

PMID- 15142806
TI  - Photosynthesis in sediments determined at high spatial resolution by the use of
      microelectrodes.
AB  - The present study investigated photosynthetic rates and their regulation by light
      within the upper 5mm of sediment in a tidal area of Niida River in Hachinohe,
      Japan. Steady-state concentration profiles of O(2), NH(4)(+), NO(2)(-), H(2)S,
      and pH in the sediment were measured with microelectrodes. Microzonation of O(2)
      respiration, denitrification and SO(4)(2-) reduction was found in the sediment.
      When light intensities exceeded 1050 micromol photons/m(2)/s, net photosynthetic
      activity was detected in the upper 0.5mm of the microbial mat colonizing on the
      sediment surface in the tidal area. In contrast, gross photosynthetic activity
      was detected in the upper 1.0mm of the microbial mat at 1900 micromol
      photons/m(2)/s. As light intensity increased, the net photosynthetic rate and
      O(2) penetration depth increased. The maximal net photosynthetic rate and O(2)
      penetration depth were 6.1 micromol O(2)/cm(3)/h and 2.2mm, respectively, at 1900
      micromol photons/m(2)/s. Net photosynthetic rates in the microbial mat in the
      tidal area were lower than in the upstream sediment. The analysis of continuous
      O(2) concentration measurements in different layers of the microbial mat during
      artificial light-dark cycles demonstrated that the photosynthetic activity
      response to changes in light intensity was extremely fast (a few seconds) and the
      O(2) concentration in the microbial mat became stable within 200s. The
      measurement of physical and chemical parameters in river water revealed that the
      study site was relatively polluted and sunlight intensity significantly
      fluctuated temporally. These results suggested that the in situ microbial
      processes occurring in the sediment fluctuated in accordance with periodic
      fluctuations in sunlight intensity.

PMID- 15142807
TI  - Distribution of linear alkylbenzenes (LABs) in riverine and coastal environments
      in South and Southeast Asia.
AB  - This paper reports the result of sewage pollution monitoring conducted in South
      and Southeast Asia during 1998-2003 using linear alkylbenzenes (LABs) as
      molecular tracers of sewage contamination. Eighty-nine water samples collected
      from Malaysia, Vietnam, and Japan (Tokyo), and 161 surface sediment samples
      collected from Tokyo, Thailand, Malaysia, Philippines, Vietnam, Cambodia,
      Indonesia, and India were analyzed for alkylbenzenes. The concentration range of
      SigmaLABs in river water particles in Southeast Asia (<0.005-0.913 microg/L) was
      comparable to or higher than those found in Tokyo (<0.005-0.638 microg/L). I/E
      ratios (a ratio of internal to external isomers of LABs) in tropical Asian waters
      were close to the value of LABs in raw sewage ( approximately 1) and much lower
      than those in secondary effluents (3-5). This suggests that untreated or
      inadequately treated sewage is discharged into the water. SigmaLABs
      concentrations in sediments from South and Southeast Asia ranged from <0.002-42.6
      microg/g-dry with the highest concentration occurring at several populous cities.
      Low I/E ratios of the sediments with high SigmaLABs concentrations suggest a
      heavy load of untreated sewage. Clearly in view of the current data and evidence
      of the implications of sewage pollution, this paper highlights the necessity of
      the continuation of water treatment system improvement in tropical Asia.

PMID- 15142808
TI  - [Ambulatory surgery to improve quality of care].

PMID- 15142809
TI  - [How to choose a mesh for the treatment of incisional hernias?].
AB  - The incidence of recurrences after raphy for treatment of incisional hernias has
      been reported as high as 50%. So, the use of a mesh is recommended for
      reinforcement of the parietal abdominal wall in the management of incisional
      hernias. Many types of mesh are presently available with different
      characteristics. The use of a mesh requires to choose the appropriate material,
      depending on the site of the implantation and the type of performed surgical
      procedure.

PMID- 15142811
TI  - [A comparative study of the feasibility and limits of ambulatory surgery in
      infants under and over one year of age].
AB  - OBJECTIVE: Outpatient surgery in pediatrics is attractive for several reasons.
      Although 6-8 months has been generally acknowledged as the lower age limit, no
      minimal age has been clearly established. This study evaluated the outcomes and
      limits of outpatient surgery in infants from 4 months to 1 year of age. MATERIAL
      AND METHODS: Between 1996 and 2003, 935 patients were admitted to our hospital
      for outpatient surgery; of these, 152 were between 4 months and 1 year (mean: 6
      months). The indications were essentially surgery to the external genitalia and
      surgery to remove hernias. The following were exclusion criteria: age below 4
      months, ASA scores equal to or above 3, and premature birth with either
      respiratory distress syndrome or a near-miss of sudden death. RESULTS: More than
      98% of the infants met the criteria for outpatient surgery. Cancellations (1.97
      vs. 0.51%, P > 0.05), conversions to classic hospitalization (0.65 vs. 0.37%, P >
      0.05), postoperative complications (0.65 vs. 0.25%, P > 0.05), rehospitalization
      (0.65 vs.0.25%, P > 0.05) and relapse of the initial pathology (0.65 vs. 0.63%, P
      > 0.05) were not more frequent in these infants than in infants over 1 year.
      CONCLUSION: Pediatric outpatient surgery can be proposed from the age of 4 months
      without increasing the postoperative risk, either anesthetic or surgical,
      included for selected former premature infants.

PMID- 15142810
TI  - [Evaluation of inguinal hernia management in ambulatory surgery].
AB  - AIM: To evaluate the prospects of ambulatory surgery for inguinal hernia.
      PATIENTS AND METHODS: From January 1995 to June 2001, 599 operations on inguinal
      hernias were performed. Patients were composed of 554 men and 45 women. The
      average age was 58 years (7-95). All patients were examined by their primary
      doctor on the first and the third day, and by the surgeon on the 10th day.
      RESULTS: Four hundred and eighty-one patients were operated on by ambulatory
      surgery (80.3%). The "Tension-free" technique was carried out among 495 patients
      (82.6%). Loco-regional anaesthesia was used for 499 patients (83.3%). The
      postoperative rate of complications was 10.4% (62 patients). Only 201 patients
      presented postoperative painful symptomatology (33.6%), 341 a discomfort (56.9%),
      and 57 (10%) experienced no pain. The overall satisfaction rate was 92.9%.
      CONCLUSION: Use of the "Tension-free" technique under loco-regional anaesthesia
      for inguinal hernias allows ambulatory surgery with a low rate of complications
      and high satisfaction for the patients.

PMID- 15142812
TI  - [Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from
      the endocrine tumor group (ETG)].
AB  - On July 2000, 127 gastrinomas (31.1%) were studied by the Endocrine Tumour Group
      (GTE) using a 408-patient cohort of Multiple Endocrine Neoplasia Type 1 patients.
      The aim of this study was to assess clinical, biological, surgical data as well
      as their trends over three periods (<1980-1980/1989->1990). A Zollinger-Ellison
      syndrome (SZE) was present in 96% of the cases. Mean age at the onset of the
      disease was 39.4 years. There were 55.9% of men. Synchronous liver metastasis was
      present in 7.1%. Taken independently, the positivity of the four main diagnosis
      tests decreased over the time. The diagnosis of oesophagitis increased (4.5
      29.7%), as well as the size of the resected tumours (9.9-16.8 mm). There was an
      increase in the familial background diagnosis (73.1-80%), an increasing use of
      Octreoscan scintigraphy and transduodenal ultrasound with positive detection of
      metastasis and tumours in 81.3% and 92.3%, respectively after 1991. Patients were
      operated on less frequently (96-52.5%), less frequently from the pancreas (87.5
      37.5%), and from the gastro-intestinal tract (70.8-30%). The relative percentage
      of major pancreatic resections increased (with at least removal of the duodenum
      and the pancreatic head) (10-26.7%). The operative mortality disappeared. Six out
      of the seven patients (85.7%) who benefited from major pancreatic resections
      normalized their gastrine level postoperatively versus 15% in less radical
      techniques. Overall 5 years survival was 90 +/- 4.4%. Survival increased after
      1985 (85 +/- 4.8% versus 95 +/- 3.6, P = 0.1). CONCLUSION: SZE in NEM1 were
      diagnosed at an earlier stage and were less frequently operated on. Nevertheless,
      the incidence of synchronous metastasis did not change significantly. Patients
      were mainly operated on for gastric emergencies and pancreatic tumours in order
      to prevent metastasis without mortality after 1991.

PMID- 15142814
TI  - [Single parathyroid adenoma: cervicotomy with bilateral exploration of the neck
      or minimally invasive unilateral approach?].

PMID- 15142813
TI  - [Abdominal wound injuries: diagnosis and treatment. Report of 79 cases].
AB  - INTRODUCTION: - Traditionally, penetrating abdominal wounds justify routine
      laparotomy. However, this policy can be adapted to mechanism of injury (stab or
      firearm) and accuracy of imaging procedures if they eliminate visceral injury
      thus allowing close follow up. PATIENTS AND METHODS: Retrospective study of 79
      patients (May 1995-May 2002) with a penetrating abdominal wound: (47 (59%) stab
      wounds and 32 (41 %) firearm wounds). Correlation between imaging and surgical
      findings, treatment, post-operative course were studied. RESULTS: Sixty-eight
      patients were operated on from the outset, and 11 underwent close follow-up. Of
      the 11 patients who had follow-up, (9 after stab wound and 2 after firearm
      wound), two had to be operated (1 in each group). Correlation between imaging and
      surgical findings was good in 34 (72%) patients after stab wound and in 21 (80%)
      after firearm wound; the mean number of visceral injuries was 1 and 3
      respectively. Six patients (8%) died (mortality: 2% and 16% respectively), 12
      (15%) had postoperative complications. CONCLUSION: Penetrating abdominal stab
      wounds can be treated by close follow-up if imaging excludes visceral injury.
      Firearm wounds still justify routine laparotomy due to both multiplicity of
      visceral injuries and bad prognosis.

PMID- 15142815
TI  - [Nephro-uretero-sigmoidectomy for colonic carcinoma associated with destruction
      of kidney after ureterosigmoidostomy: a case report].
AB  - A patient underwent at his birth, an ureterosigmoidostomy for exstrophic bladder.
      Fifty-six years later, she presented a carcinoma on the right
      ureterosigmoidostomy associated with chronic urinary infection. She underwent a
      right ureteronephrectomy and sigmoidectomy. Chronic alterations of the colic
      mucin by urines lead to carcinoma.

PMID- 15142817
TI  - [Neutropenia and fever after aorto-coronary bypasses].
AB  - Plasma-derived products are often used in cardiac surgery. We report the case of
      a patient developing an infection due to Parvovirus B19 after coronary artery
      bypass. Symptoms were fever, asthenia, anemia, and pancreatitis. This infection
      can be transmitted from plasma-derived product, like fibrin sealant (used for
      hemostasis during surgery). Parvovirus B19 is resistant to existing virus
      inactivating techniques. The patient had to leave our hospital after symptomatic
      treatment which has significantly increased the length to stay.

PMID- 15142816
TI  - [Diagnostic and therapeutic strategy in duodenal diverticular bleeding: report of
      two cases and review of the literature].
AB  - Host of the duodenal diverticulum are asymptomatic and located on the second part
      of the duodenum; these diverticula may induce major haemorrhage on rare
      occasions. We report on two patients who presented with massive upper
      gastrointestinal bleeding originating from a duodenal diverticulum. One patient
      was successfully treated by endoscopy and the other patient required
      diverticulectomy with successful outcome.

PMID- 15142818
TI  - [Closed thoracic drainage for purulent pleurisy].
AB  - In purulent pleuresia, thoracenthesis is the gold standard treatment.
      Fiblinolytics should be infused through the drain at an early stage in order to
      prevent or treat fibrotic encystement. The cause of the pleuresia should be
      treated parallely to the drainage.

PMID- 15142819
TI  - [Sentinel lymph node and uterine cancer].

PMID- 15142820
TI  - [Comment on the article entitled by S. Abdelmoula-Marzouki et al.: Tubo-ovarian
      actinomycosis ruptured into the sigmoid colon (Ann chir 2003; 128: 719-721)].

PMID- 15142821
TI  - Various approaches to modify biomaterial surfaces for improving
      hemocompatibility.
AB  - In this paper, the mechanism of thrombus formation on the surface of polymeric
      materials and the various approaches of modifying biomaterial surfaces to improve
      their hemocompatibility are reviewed. Moreover, the blood compatibility of the
      cellulose membrane grafted with O-butyrylchitosan (OBCS) by using a radiation
      grafting technique was studied. Surface analysis of grafted cellulose membrane
      was verified by attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR) and electron spectroscopy for chemical analysis (ESCA),
      which confirmed that OBCS was successfully grafted onto the cellulose membrane
      surfaces. Blood compatibility of the grafted cellulose membranes was evaluated by
      platelet rich plasma (PRP) contacting experiments and protein adsorption
      experiments using blank cellulose membranes as the control. The blood
      compatibility of OBCS grafted cellulose membranes is better than that of blank
      cellulose membranes. These results suggest that the photocrosslinkable chitosan
      developed here has the potential of serving in blood-contacting applications in
      medical use.

PMID- 15142822
TI  - Chemistry of alumina, reactions in aqueous solution and its application in water
      treatment.
AB  - Due to the presence and significance of alumina in the natural aquatic
      environment and its increasing application in drinking and wastewater
      purification, the knowledge of the structure of alumina and its possible
      interactions with organic and inorganic compounds in water are of great
      importance. This is of particular importance in both the understanding of natural
      aquatic environment processes and efficient industrial applications. The
      chemistry of alumina reactions in water is complex. The adsorption ability of
      alumina towards organic and inorganic compounds might be influenced by several
      factors such as: surface characteristics of the adsorbent (surface area, density,
      pore volume, porosity, pore size distribution, pH(PZC) as well as mechanical
      strength and purity), pH of the solution, ionic strength, composition of water
      and the physicochemical properties of adsorbates. The aim of this paper is to
      give a brief review of the properties of alumina and its reactivity with organic
      and inorganic compounds present in aqueous solutions. It also summarises the
      usage of alumina and alumina supported phases in water treatment technology.

PMID- 15142823
TI  - Preparation of metal nanoparticles in water-in-oil (w/o) microemulsions.
AB  - The use of an inorganic phase in water-in-oil microemulsions has received
      considerable attention for preparing metal particles. This is a new technique,
      which allows preparation of ultrafine metal particles within the size range 5
      nm<particle diameter<50 nm. This article presents a review of the current
      literature in the field of particle preparation of several metals such as silver,
      copper, cadmium, cobalt, nickel, cadmium and gold in the inverse microemulsion
      systems. The reactant metal salts and reducing agents are mostly soluble in water
      and therefore the nucleation of metal particles proceeds in the water pools of
      the microemulsion. The rate of particle nucleation is a function of the
      percolation degree of microemulsion droplets. Besides a short introduction into
      some aspects of the microemulsion types and formation, we mainly focus on the
      kinetics of metallic particle formation. Effects of stabilizer (emulsifier) type
      and concentration and the type of continuous phase, reducing agent and additive
      on the particle formation are summarized and evaluated. The influence of several
      other parameters such as temperature, the incident light, the nature of metal
      salts and reaction conditions are also reviewed. These results indicate that the
      nature of the stabilizer emulsifier, the surface activity of additives and the
      colloidal stability of microemulsion droplets play decisive role on the particle
      size and distribution during the preparation of metal particles.

PMID- 15142825
TI  - Overview of geriatric distance education for academic courses and continuing
      education.
AB  - Distance education technologies may be applied to academic settings, continuing
      education/continuing medical education settings or in combination to both. This
      article provides an overview of what we have learned about academic and
      continuing education/continuing medical education in geriatrics and gerontology.
      It includes information on the scope of distance education, the strengths and
      challenges of distance education, and discusses issues related to technology,
      intellectual property, instructional design and curriculum development,
      collaborative effort, marketing, evaluation, and research.

PMID- 15142826
TI  - Interdisciplinary gerontology education online:a developmental process model.
AB  - Distance education online in gerontology in academic settings is designed to
      reflect content relevant to gerontology practices, academic standards, teaching
      strategies, and technology that embrace content delivery while enhancing
      learning. A balance with community services and needs for older adult
      populations, academic integrity, stakeholders, and resources, with an
      interdisciplinary and multidisciplinary student-centered approach are important.
      Considering these factors and based on a needs assessment, this article describes
      a process model used to create an interdisciplinary gerontology education program
      for online delivery at Florida Gulf Coast University (FGCU). The realities,
      pearls of wisdom, and lessons learned from creating and implementing the FGCU
      online interdisciplinary undergraduate gerontology education in the academic
      setting are also presented.

PMID- 15142827
TI  - Using online modules is a multi-modality teaching system: a high-touch high-tech
      approach to geriatric education.
AB  - Making geriatric education available to rural faculty/preceptors, students, and
      practitioners presents many challenges. Often the only options considered for
      educating those in the health professions about geriatrics are either traditional
      face-to-face courses or distance education programs. The purpose of this paper
      was to examine the use of Web-based modules or courses and other distance
      learning technology in concert with traditional learning modalities. The Mountain
      State Geriatric Education Center explored the use of a multi-modal approach
      within a high-touch, high-tech framework. Our findings indicate the following: it
      is important to start where participants are ready to begin; flexibility and
      variety are needed; soliciting evaluative feedback from participants is valuable;
      there is a need to integrate distance learning with more traditional modalities;
      and a high-tech, high-touch approach provides a format which participants find
      acceptable, accessible, and attractive. This assertion does not rule out the use
      of technology for distance education but rather encourages educators to take
      advantage of a wide range of modalities, traditional and technological, to reach
      rural practitioners, faculty, and students.

PMID- 15142828
TI  - Harnessing technology and collaboration for an online ethnogeriatric educational
      resource.
AB  - The paper describes the development and testing of a Web-based educational
      resource for usability and acceptability by health care providers who care for
      ethnic older adults. The work was undertaken as a dissertation project. The
      purpose of the Website is to provide on-demand ethnogeriatric information to
      enhance provider-patient interaction. Focus groups of clinicians and ethnic older
      adults were used in order to identify content relevant to the care of frail
      ethnic older adults. Collaboration with the Stanford Geriatric Education Center,
      On Lok SeniorHealth Services, Inc., Pepperdine University Graduate School of
      Education, and a network of virtual consultants provided support to the project.
      The site contains information on 15 cultures, 12 religions, and 6 ethnic minority
      cohort groups. Testing by snowball sampling generated survey data from 96
      respondents, consisting of general practitioners (24%), pediatric specialists
      (20%), and geriatric specialists (18%). The Website was considered useful for
      provider-patient communication (77%) and would be recommended to others (99%).
      The Web-based information resource, called "Diversity, Healing, and Healthcare,"
      currently exists as a resource rather than as a defined learning module and can
      be accessed at http://www.gasi. org/diversity.htm.

PMID- 15142829
TI  - Designing health care risk management on-line:meeting regulators' concerns for
      fixed-hour curriculum.
AB  - This paper describes the experience of creating a continuing professional
      education on-line risk management program that is designed to meet Florida's
      educational requirements for licensure as a risk manager in health-care settings
      and details the challenges faced when the in-class didactic program of 15 eight
      hour sessions is reformatted as an on-line program. Structuring
      instructor/learner interactivity remains a challenge, especially if the program
      allows learner control and is a key feature in marketing the program. The article
      presents the dilemmas for state regulators as they work to determine if the on
      line program meets legislative intent and statutory requirements because the
      learning platform does not have a clock function that accumulates time for each
      learner. While some details reflect the uniqueness of the 120-hour educational
      requirements for risk managers in Florida, the experience of the authors provides
      insight into the development of continuing professional education distance
      learning programs that are multidisciplinary and move primarily from a time-based
      format into a curriculum that uses time as only one dimension of the evaluation
      of learning.

PMID- 15142830
TI  - When and where you want it: continuing education from a distance.
AB  - Online technology is increasingly being used as a tool for delivery of continuing
      education to health care professionals. This paper discusses key lessons learned
      in developing a distance-learning program. It provides practical information on
      ways to enhance interactivity and overcome obstacles. Preliminary outcomes for
      learners in a four-state area are summarized.

PMID- 15142831
TI  - Smooth muscle overexpression of IGF-I induces a novel adaptive response to small
      bowel resection.
AB  - Prior studies of intestinal adaptation after massive small bowel resection (SBR)
      have focused on growth factors and their effects on amplification of the gut
      mucosa. Because adaptive changes have also been described in intestinal smooth
      muscle, we sought to determine the effect of targeted smooth muscle growth factor
      overexpression on resection-induced intestinal adaptation. Male transgenic mice
      with smooth muscle cell overexpression of insulin-like growth factor I (IGF-I) by
      virtue of an alpha-smooth muscle actin promoter were obtained. SMP8 IGF-I
      transgenic (IGF-I TG) and nontransgenic (NT) littermates underwent 50% proximal
      SBR or sham operation and were then killed after 3 or 28 days. NT mice showed the
      expected alterations in mucosal adaptive parameters after SBR, such as increased
      wet weight and villus height. The IGF-I TG mice had inherently taller villi,
      which did not increase significantly after SBR. In addition, IGF-I TG mice had a
      50% postresection persistent increase in remnant intestinal length, which was
      associated with an early decline and later increase in relative mucosal surface
      area. These results indicate that growth factor overexpression within the
      muscularis layer of the bowel wall induces significant postresection adaptive
      intestinal lengthening and a unique mucosal response. IGF-I signaling within the
      muscle wall may play an important role in the pathogenesis of resection-induced
      adaptation.

PMID- 15142833
TI  - Estrogen receptor-alpha expression in osmosensitive elements of the lamina
      terminalis: regulation by hypertonicity.
AB  - The subfornical organ (SFO), median preoptic nucleus (MnPO), and organum
      vasculosum lamina terminalis (OVLT), which are associated with the lamina
      terminalis, are important in the control of body fluid balance. Neurons in these
      regions express estrogen receptor (ER)-alpha, but whether the ER-alpha neurons
      are activated by hypertonicity and whether hypertonicity regulates ER-alpha
      expression are not known. Using fluorescent, double-label immunocytochemistry, we
      examined the expression of ER-alpha-immunoreactivity (ir) and Fos-ir in control
      and water-deprived male rats. In control animals, numerous ER-alpha-positive
      neurons were expressed in the periphery of the SFO, in both the dorsal and
      ventral MnPO, and in the dorsal cap of the OVLT. Fos-positive neurons were sparse
      in euhydrated rats but were numerous in the SFO, MnPO, and the dorsal cap of the
      OVLT after 48-h water deprivation. Most ER-alpha-ir neurons in these areas were
      positive for Fos, indicating a significant degree of colocalization. To examine
      the effect of dehydration on ER-alpha expression, animals with and without
      lesions surrounding the anterior and ventral portion of the 3rd ventricle (AV3V)
      were water deprived for 48 h. Water deprivation resulted in a moderate increase
      in ER-alpha-ir in the SFO of sham-lesioned rats (P = 0.03) and a dramatic
      elevation in AV3V-lesioned animals (P < 0.05). This was probably induced by the
      significant increase in plasma osmolality in both dehydrated groups (P < 0.001)
      rather than a decrease in blood volume, because hematocrit was significantly
      increased only in the dehydrated sham-lesioned animals. Thus these studies
      implicate the osmosensitive regions of the lamina terminalis as possible targets
      for sex steroid effects on body fluid homeostasis.

PMID- 15142832
TI  - Patency of the preterm fetal ductus arteriosus is regulated by endothelial nitric
      oxide synthase and is independent of vasa vasorum in the mouse.
AB  - Patency of the fetal ductus arteriosus (DA) is maintained in an environment of
      low relative oxygen tension and a preponderance of vasodilating forces. In
      addition to prostaglandins, nitric oxide (NO), a potent vasodilator in the
      pulmonary and systemic vasculatures, has been implicated in regulation of the
      fetal DA. To further define the contribution of NO to DA patency, the expression
      and function of NO synthase (NOS) isoforms were examined in the mouse DA on days
      17-19 of pregnancy and after birth. Our results show that endothelial NOS (eNOS)
      is the predominant isoform expressed in the mouse DA and is localized in the DA
      endothelium by in situ hybridization. Despite rapid constriction of the DA after
      birth, eNOS expression levels were unchanged throughout the fetal and postnatal
      period. Pharmacological inhibition of prostaglandin vs. NO synthesis in vivo
      showed that the preterm fetal DA on day 16 is more sensitive to NOS inhibition
      than the mature fetal DA on day 19, whereas prostaglandin inhibition results in
      marked DA constriction on day 19 but minimal effects on the day 16 DA. Combined
      prostaglandin and NO inhibition caused additional DA constriction on day 16. The
      contribution of vasa vasorum to DA regulation was also examined. Immunoreactive
      platelet endothelial cell adhesion molecule and lacZ tagged FLK1 localized to DA
      endothelial cells but revealed the absence of vasa vasorum within the DA wall.
      Similarly, there was no evidence of vasa vasorum by vascular casting. These
      studies indicate that eNOS is the primary source of NO in the mouse DA and that
      vasomotor tone of the preterm fetal mouse DA is regulated by eNOS-derived NO and
      is potentiated by prostaglandins. In contrast to other species, mechanisms for DA
      patency and closure appear to be independent of any contribution of the vasa
      vasorum.

PMID- 15142834
TI  - Contractile properties of human placental anchoring villi.
AB  - The presence of myofibroblasts arranged parallel to the longitudinal axes of
      anchoring villi of the placenta has previously been described. Furthermore, it
      has been suggested that intraplacental blood volume, and hence fetal-maternal
      oxygen-nutrient exchange, may in part be regulated through the longitudinal
      contraction of anchoring villi. We demonstrate here that anchoring villi have the
      ability to contract and relax longitudinally. Anchoring villi from normal term
      human placentae were dissected and suspended from force-displacement transducers
      to determine their longitudinal contractility in response to potassium chloride
      (KCl), N(omega)-nitro-l-arginine methyl ester (l-NAME) and the nitric oxide
      donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN). Treatment with
      both KCl and l-NAME resulted in up to a 62% and 74% increase, respectively, in
      longitudinal contraction over resting tone. In contrast, both SNP and GTN caused
      a dose-dependent relaxation of precontracted villi. Immunohistochemistry of
      longitudinal sections of villi confirmed the presence of alpha-actin-containing
      cells in the extravascular space. Histological staining with hemotoxylin and
      eosin confirm that the tissue used in these experiments were anchoring villi.
      These findings suggest that the contraction of anchoring villi may be an
      important mechanism whereby the placenta may regulate intraplacental volume.

PMID- 15142835
TI  - Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats.
AB  - Chronic consumption of ethanol in adult rats and humans leads to reduced AVP
      producing neurons, and prenatal ethanol (PE) exposure has been reported to cause
      changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus
      of young rats. The present studies further characterize the effects of PE
      exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary
      storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet
      with 35% of the calories from ethanol or a control liquid diet for days 7-22 of
      pregnancy. Water consumption and urine excretion rate were measured in the
      offspring at 60-68 days of age. Subsequently, the offspring were infused with 5%
      NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40
      min intervals during infusion for measurement of AVP and osmolality. Urine output
      and water intake were approximately 20% greater in PE-exposed rats than in rats
      with no PE exposure, and female rats had a greater water intake than males. The
      relationship between plasma osmolality and AVP in PE-exposed rats was parallel
      to, but shifted to the right of, the control rats, indicating an increase in
      osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and
      hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data
      suggest that PE exposure can cause a permanent condition of a mild partial
      central diabetes insipidus.

PMID- 15142837
TI  - Prenatal blockade of estradiol synthesis impairs respiratory and metabolic
      responses to hypoxia in newborn and adult rats.
AB  - We tested the hypothesis that estradiol modifies respiratory control in pregnant
      rats and participates in the development of respiratory chemoreflexes in fetuses.
      Pregnant rats (n = 12) received daily subcutaneous injections of vehicle (Veh, n
      = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol
      synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery.
      Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen
      consumption (Vo(2))] were determined at G14 and G20, in pups [on postnatal day 3
      (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers.
      Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O(2) and in
      P20 or P70 rats by moderate hypoxia (12% O(2), 30 min). ATD treatment reduced
      circulating estradiol in pregnant dams at G20 without producing changes in the
      circulating level of estradiol precursors (testosterone and androstenedione). ATD
      treated dams showed impaired respiratory adjustment to late gestation. Pups born
      to ATD mothers had higher resting Vo(2) (+23% at P3, +21% at P20), respiratory
      frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at
      P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic
      exposure at P3 was -9.7% in Veh (P < 0.05 vs. room air) and only -2.6% (P = not
      significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was
      attenuated compared with Veh. In P20 and P70 rats, the drop of Vo(2) in hypoxia (
      31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol
      secreted during late gestation is necessary for respiratory adjustment to
      pregnancy and is required for adequate development of respiratory and metabolic
      control in the offspring.

PMID- 15142836
TI  - Circulating free nitrotyrosine in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular
      disease, endothelial dysfunction, and oxidative stress, generated by repetitive
      nocturnal hypoxemia and reperfusion. Circulating free nitrotyrosine has been
      reported as a novel biomarker of nitric oxide (NO)-induced oxidative/nitrosative
      stress. Nitrosative stress has been implicated as a possible mechanism for
      development of cardiovascular diseases. We tested the hypothesis that repetitive
      severe hypoxemia resulting from OSA would increase NO-mediated oxidative stress.
      We studied 10 men with newly diagnosed moderate to severe OSA who were free of
      other diseases, had never been treated for OSA, and were taking no medications.
      Nitrotyrosine measurements, performed by liquid chromatography-tandem mass
      spectrometry, were made before and after untreated apneic sleep. We compared free
      nitrotyrosine levels in these patients with those obtained at similar times in 10
      healthy male control subjects without OSA, with similar age and body mass index.
      Evening baseline nitrotyrosine levels were similar before sleep in the control
      and OSA groups [0.16 +/- 0.01 and 0.15 +/- 0.01 ng/ml, respectively, P = not
      significant (NS)]. Neither normal nor disturbed apneic sleep led to significant
      changes of plasma nitrotyrosine (morning levels: control group 0.14 +/- 0.01
      ng/ml; OSA group 0.15 +/- 0.01 ng/ml, P = NS). OSA was not accompanied by
      increased circulating free nitrotyrosine either at baseline or after sleep. This
      observation suggests that repetitive hypoxemia during OSA does not result in
      increased NO-mediated oxidative/nitrosative stress in otherwise healthy subjects
      with OSA.

PMID- 15142838
TI  - Single muscle fiber contractile properties during a competitive season in male
      runners.
AB  - The purpose of this investigation was to examine the contractile properties of
      individual myofibers in response to periodized training periods throughout a
      collegiate cross-country season in male runners. Muscle biopsies of the
      gastrocnemius were taken after a summer base training phase (T1), an 8-wk intense
      training period (T2), and a 4-wk taper phase (T3). Five runners (n = 5; age = 20
      +/- 1 yr; wt = 65 +/- 4 kg; ht = 178 +/- 3 cm) completed all three time points. A
      total of 328 individual muscle fibers [myosin heavy chain (MHC) I = 66%; MHC IIa
      = 33%; hybrids = 1%] were isolated and studied at 15 degrees C for their
      contractile properties. Diameter of MHC I fibers was 3% smaller (P < 0.05) at T2
      compared with T1 and an additional 4% smaller (P < 0.05) after the taper. Cell
      size was unaltered in the MHC IIa fibers. MHC I and IIa fiber strength increased
      18 and 11% (P < 0.05), respectively, from T1 to T2. MHC I fibers produced 9% less
      force (P < 0.05) after the taper, whereas MHC IIa fibers were 9% stronger (P <
      0.05). Specific tension increased 38 and 26% (P < 0.05) for MHC I and IIa fibers,
      respectively, from T1 to T2 and was unchanged with the taper. Maximal shortening
      velocity (Vo) of the MHC I fibers decreased 23% (P < 0.05) from T1 to T2 and 17%
      (P < 0.05) from T2 to T3, whereas MHC IIa Vo was unchanged. MHC I peak power
      decreased 20% (P < 0.05) from T1 to T2 and 25% (P < 0.05) from T2 to T3, whereas
      MHC IIa peak power was unchanged. Power corrected for cell size decreased 15% (P
      < 0.05) from T2 to T3 and was 24% (P < 0.05) lower at T3 compared with T1 for the
      MHC I fibers only. These data suggest that changes in run training alter
      myocellular physiology via decreases in fiber size, Vo, and power of MHC I fibers
      and through increases in force per cross-sectional area of slow- and fast-twitch
      muscle fibers.

PMID- 15142840
TI  - Atrioventricular nonuniformity of pericardial constraint.
AB  - Physiologists and clinicians commonly refer to "pressure" as a measure of the
      constraining effects of the pericardium; however, "pericardial pressure" is
      really a local measurement of epicardial radial stress. During diastole, from the
      bottom of the y descent to the beginning of the a wave, pericardial pressure over
      the right atrium (P(pRA)) is approximately equal to that over the right ventricle
      (P(pRV)). However, in systole, during the interval between the bottom of the x
      descent and the peak of the v wave, these two pericardial pressures appear to be
      completely decoupled in that P(pRV) decreases, whereas P(pRA) remains constant or
      increases. This decoupling indicates considerable mechanical independence between
      the RA and RV during systole. That is, RV systolic emptying lowers P(pRV), but
      P(pRA) continues to increase, suggesting that the relation of the pericardium to
      the RA must allow effective constraint, even though the pericardium over the RV
      is simultaneously slack. In conclusion, we measured the pericardial pressure
      responsible for the previously reported nonuniformity of pericardial strain.
      P(pRA) and P(pRV) are closely coupled during diastole, but during systole they
      become decoupled. Systolic nonuniformity of pericardial constraint may augment
      the atrioventricular valve-opening pressure gradient in early diastole and, so,
      affect ventricular filling.

PMID- 15142839
TI  - Evidence of nanobacterial-like structures in calcified human arteries and cardiac
      valves.
AB  - Mechanisms mediating vascular calcification remain incompletely understood.
      Nanometer scale objects hypothesized to be a type of bacteria (nanobacteria) are
      associated with calcified geological specimens, human kidney stones, and psammona
      bodies in ovarian cancer. Experiments were designed to evaluate human vascular
      tissue for the presence of similar nanometer-scale objects. Calcified human
      aneurysms (n = 8), carotid plaques (n = 2), femoral arterial plaques (n = 2), and
      cardiac valves (n = 2) and noncalcified aneurysms from patients with bicuspid
      aortic valve disease (n = 2) were collected as surgical waste from the Heart
      Hospital of Austin, Austin, Texas, and Mayo Clinic, Rochester, Minnesota. Whole
      mounts or adjacent sections from each specimen were examined by electron
      microscopy, stained for calcium phosphate, or stained with a commercially
      available antibody (8D10). Filtered (0.2 microm) homogenates of aneurysms were
      cultured and costained with 8D10 antibody followed by PicoGreen to detect DNA or
      incubated with [3H]uridine. Staining for calcium phosphate was heterogeneously
      distributed within all calcified tissues. Immunological staining with 8D10 was
      also heterogeneously distributed in areas with and without calcium phosphate.
      Analysis of areas with positive immunostaining identified spheres ranging in size
      from 30 to 100 nm with a spectral pattern of calcium and phosphorus (high-energy
      dispersive spectroscopy). Nanosized particles cultured from calcified but not
      from noncalcified aneurysms were recognized by a DNA-specific dye and
      incorporated radiolabeled uridine, and, after decalcification, they appeared via
      electron microscopy to contain cell walls. Therefore, nanometer-scale particles
      similar to those described as nanobacteria isolated from geological specimens and
      human kidney stones can be visualized in and cultured from calcified human
      cardiovascular tissue.

PMID- 15142841
TI  - NF-kappaB activation is required for the development of cardiac hypertrophy in
      vivo.
AB  - In the present study, we examined whether NF-kappaB activation is required for
      cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic
      banding for 1, 3, and 5 days and 1-6 wk, and age-matched sham-operated rats
      served as controls. In a separate group of rats, an IkappaB-alpha dominant
      negative mutant (IkappaB-alphaM), a superrepressor of NF-kappaB activation, or
      pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-kappaB
      activation, was administered to aortic-banded rats for 3 wk. The heart weight-to
      body weight ratio was significantly increased at 5 days after aortic banding,
      peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham
      controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA
      expressions were significantly increased after 1 wk of aortic banding, reached a
      maximum between 2 and 3 wk, and remained increased at 6 wk compared with age
      matched sham controls. NF-kappaB activity was significantly increased at 1 day,
      reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-beta activity was
      significantly increased at 1 day, peaked at 5 days, and then decreased but
      remained elevated at 6 wk after aortic banding compared with age-matched sham
      controls. Inhibiting NF-kappaB activation in vivo by cardiac transfection of
      IkappaB-alphaM or by PDTC treatment significantly attenuated the development of
      cardiac hypertrophy in vivo with a concomitant decrease in NF-kappaB activity.
      Our results suggest that NF-kappaB activation is required for the development of
      cardiac hypertrophy in vivo and that NF-kappaB could be an important target for
      inhibiting the development of cardiac hypertrophy in vivo.

PMID- 15142842
TI  - Differential activation of potassium channels in cerebral and hindquarter
      arteries of rats during simulated microgravity.
AB  - The purpose of this study was to test the hypothesis that differential
      autoregulation of cerebral and hindquarter arteries during simulated microgravity
      is mediated or modulated by differential activation of K(+) channels in vascular
      smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague
      Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the
      cardiovascular deconditioning effect due to short- and medium-term microgravity.
      K(+) channel function of VSMCs was studied by pharmacological methods and patch
      clamp techniques. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) and voltage
      gated K(+) (K(v)) currents were determined by subtracting the current recorded
      after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4
      aminopyridine (4-AP), respectively, from that of before. For cerebral vessels,
      the normalized contractility of basilar arterial rings to TEA, a BK(Ca) blocker,
      and 4-AP, a K(v) blocker, was significantly decreased after 1- and 4-wk simulated
      microgravity, respectively. VSMCs isolated from the middle cerebral artery
      branches of suspended rats had a more depolarized membrane potential (E(m)) and a
      smaller K(+) current density compared with those of control rats. Furthermore,
      the reduced total current density was due to smaller BK(Ca) and smaller K(v)
      current density in cerebral VSMCs after 1- and 4-wk tail suspension,
      respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order
      small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative
      E(m) and larger K(+) current densities for total, BK(Ca), and K(v) currents.
      These results indicate that differential activation of K(+) channels occur in
      cerebral and hindquarter VSMCs during short- and medium-term simulated
      microgravity. It is further suggested that different profiles of channel
      remodeling might occur in VSMCs as one of the important underlying cellular
      mechanisms to mediate and modulate differential vascular adaptation during
      microgravity.

PMID- 15142843
TI  - Degradation of rat cardiac troponin I during ischemia independent of reperfusion.
AB  - Cardiac troponin I (cTnI) degradation has been noted in the stunned myocardium of
      rodents after ischemia and reperfusion and is one proposed mechanism for the
      decreased left ventricular (LV) contractility in postischemic hearts. cTnI
      degradation has been best described after reperfusion of the ischemic myocardium.
      The effect of ischemia, independent of reperfusion, on cTnI breakdown has not
      been well characterized. We tested the hypothesis that progressive cTnI
      degradation occurs with increasing durations of ischemia and that this ischemia
      based degradation is, in part, oxidant mediated. Isolated perfused rat hearts
      underwent global ischemia of 15, 20, or 25 min with and without reperfusion. A
      second series of hearts was treated with the antioxidants tiron (10 mM) and N
      acetylcysteine (4 mM) before 20 min of global ischemia without reperfusion. cTnI
      degradation was measured using a cTnI-specific antibody and Western blot
      analyses. A progressive increase in cTnI degradation was seen with increasing
      duration of ischemia (no reperfusion), which correlated with the return of LV
      developed pressure during reperfusion. The extent of cTnI degradation was
      increased in hearts pretreated with antioxidants, although the qualitative
      degradation pattern was not altered. We conclude that a time-dependent cTnI
      breakdown occurs during global ischemia that is independent of reperfusion. cTnI
      breakdown during ischemia is further increased in the presence of antioxidants,
      suggesting ROS generated during ischemia may play a cTnI protective role.

PMID- 15142844
TI  - Contribution of Akt and endothelial nitric oxide synthase to diazoxide-induced
      late preconditioning.
AB  - The opening of mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels has a
      significant role in delayed ischemic preconditioning, and nitric oxide (NO) is a
      well-known trigger for its activation. However, the source of NO remains unknown.
      Phosphorylation of endothelial NO synthase (eNOS) increases NO production and
      reduces apoptosis through the Akt signaling pathway. To elucidate the Akt
      signaling pathway involved in the opening and antiapoptotic effect of mitoKATP
      channel during delayed pharmacological preconditioning, the mitoKATP channel
      opener diazoxide (DE, 7 microg/kg i.p.) alone or DE plus Nomega-nitro-L-arginine
      methyl ester (L-NAME, 30 microg/kg i.v.), an inhibitor of NOS, or wortmannin
      (WTN, 15 microg/kg i.v.), an inhibitor of phosphatidylinositol 3'-kinase (PI3
      kinase), was administered to wild-type (WT) or eNOS(-/-) mice during DE
      treatment. Twenty-four hours later, hearts were isolated and subjected to 40 min
      ischemia and 30 min reperfusion (I/R). The effect of DE and other interventions
      on hemodynamic, terminal dUTP nick-end labeling staining and biochemical changes
      during I/R was assessed in mouse hearts. Treatment with DE resulted in a 2.2-fold
      increase in phosphorylation of Akt and a significant increase in eNOS and
      inducible NOS (iNOS) proteins. Akt is upstream of NOS and the mitoKATP channel as
      simultaneous pretreatment of WTN with DE abolished phosphorylation of Akt, which
      was not affected by L-NAME and 5-hydroxydecanoate. In hearts treated with DE,
      cardiac function was significantly improved after I/R, and apoptosis was also
      significantly decreased. WTN abolished the antiapoptotic effect of DE. Similarly,
      S-methylisothiourea, a specific iNOS inhibitor, when given to eNOS(-/-) mice that
      were pretreated with DE completely abolished the beneficial effects of DE on
      reduction of apoptotic death. DE was partially effective in eNOS(-/-) mice
      against the ischemic injury. It is concluded that DE activates Akt through the
      PI3 kinase signaling pathway and iNOS and eNOS is downstream of Akt.

PMID- 15142845
TI  - Computer model of action potential of mouse ventricular myocytes.
AB  - We have developed a mathematical model of the mouse ventricular myocyte action
      potential (AP) from voltage-clamp data of the underlying currents and Ca2+
      transients. Wherever possible, we used Markov models to represent the molecular
      structure and function of ion channels. The model includes detailed intracellular
      Ca2+ dynamics, with simulations of localized events such as sarcoplasmic Ca2+
      release into a small intracellular volume bounded by the sarcolemma and
      sarcoplasmic reticulum. Transporter-mediated Ca2+ fluxes from the bulk cytosol
      are closely matched to the experimentally reported values and predict stimulation
      rate-dependent changes in Ca2+ transients. Our model reproduces the properties of
      cardiac myocytes from two different regions of the heart: the apex and the
      septum. The septum has a relatively prolonged AP, which reflects a relatively
      small contribution from the rapid transient outward K+ current in the septum. The
      attribution of putative molecular bases for several of the component currents
      enables our mouse model to be used to simulate the behavior of genetically
      modified transgenic mice.

PMID- 15142846
TI  - Ghrelin induces vasoconstriction in the rat coronary vasculature without altering
      cardiac peptide secretion.
AB  - We administered ghrelin, a novel growth hormone-releasing hormone, to isolated
      perfused rat hearts, coronary arterioles, and cultured neonatal cardiomyocytes to
      determine its effects on coronary vascular tone, contractility, and natriuretic
      peptide secretion and gene expression. We also determined cardiac levels of
      ghrelin and whether the heart is a source of the circulating peptide. Ghrelin
      dose dependently increased coronary perfusion pressure (44 +/- 9%, P < 0.01),
      constricted isolated coronary arterioles (12 +/- 2%, P < 0.05), and significantly
      enhanced the pressure-induced myogenic tone of arterioles. These effects were
      blocked by diltiazem, an L-type Ca(2+) channel blocker, and bisindolylmaleimide
      (Bis), a protein kinase C (PKC) inhibitor. Interestingly, coinfusion of ghrelin
      with diltiazem completely restored myocardial contractile function that was
      decreased 30 +/- 3% (P < 0.01) by diltiazem alone. In contrast, combination of
      ghrelin with diltiazem or Bis did not significantly alter atrial natriuretic
      peptide (ANP) secretion, which was decreased 40% (P < 0.01) and 50% (P < 0.05) by
      these agents alone, respectively. Administration of ghrelin to cultured
      cardiomyocytes had no effect on ANP or B-type natriuretic peptide secretion or
      gene expression. Detectable amounts of low-molecular-weight ghrelin were present
      in cardiac tissue extracts but not in isolated heart perfusate. Thus we provide
      the first evidence that ghrelin has a coronary vasoconstrictor action that is
      dependent on Ca(2+) and PKC. Furthermore, the data obtained from diltiazem
      infusion suggest that ghrelin has a role in regulation of contractility when L
      type Ca(2+) channels are blocked. Finally, the observation that immunoreactive
      ghrelin is found in cardiac tissue suggests the presence of a local cardiac
      ghrelin system.

PMID- 15142847
TI  - Effects of aging on the cardiac remodeling induced by chronic high-altitude
      hypoxia in rat.
AB  - Effects of chronic high-altitude hypoxia on the remodeling of right ventricle
      were examined in three age groups of rats: 2, 6, and 18 mo. The extent of right
      ventricular (RV) hypertrophy (RVH) showed an age-associated diminution. RV cell
      size and pericellular fibrosis showed a significant increase in the 2- and 6-mo
      old exposed rats but not in the 18-mo-old exposed rats compared with control. A
      hyperplasic response was underscored in the three exposed age groups but appeared
      less pronounced in the 18-mo-old rats. A significant decrease in the transient
      outward potassium current (Ito) density was observed in RV cell only in the 2-mo
      old exposed group compared with the control group. In the control group, there
      was a clear tendency for Ito density to decrease as a function of age. The
      sustained outward current density was modified neither by the hypoxia condition
      nor by the age. Neither the cytochrome c oxidase activity nor the heat shock
      protein 72 content in the RV was altered after hypoxic exposure regardless of
      age. The norepinephrine content in the RV was significantly decreased in each age
      group exposed to hypoxia when compared with their age-matched control group. Our
      findings indicate that the remodeling (at morphological and electrophysiological
      levels) induced by chronic hypoxia in the RV can be decreased by the natural
      aging process.

PMID- 15142849
TI  - A comparison of oxidized LDL-induced collagen secretion by graft and aortic SMCs:
      role of PDGF.
AB  - Smooth muscle cells (SMCs) from prosthetic vascular grafts constitutively secrete
      higher levels of collagen than aortic SMCs. Lipid oxidation products accumulate
      in grafts, and we postulated that they stimulate SMC production of collagen. The
      effect of oxidized low-density lipoprotein (oxLDL) on type I collagen secretion
      by aortic and graft SMCs was compared. SMCs isolated from the canine thoracic
      aorta or Dacron thoracoabdominal grafts (n = 10) were incubated with native LDL
      or oxLDL (0-400 microg cholesterol/ml) for 72 h. Type I collagen in the
      conditioned medium was measured by ELISA. OxLDL increased collagen production by
      graft SMCs from 4.1 +/- 0.3 to 11.0 +/- 0.4 ng/microg DNA and by aortic SMCs from
      2.3 +/- 0.1 to 3.5 +/- 0.2 ng/microg DNA. Native LDL had little effect. LY-83583,
      a superoxide generator, stimulated a dramatic increase in collagen secretion by
      graft SMCs and a smaller but significant elevation by aortic SMCs. OxLDL has been
      shown to increase PDGF production by graft SMCs, and PDGF can stimulate collagen
      production. Anti-PDGF antibody inhibited the increase in collagen production by
      graft SMCs that was stimulated by oxLDL, implicating PDGF as one mechanism of
      oxLDL-induced collagen production. Lipid oxidation products that accumulate in
      prosthetic vascular grafts can cause an oxidative stress that stimulates PDGF
      production by graft SMCs that in turn stimulates collagen production,
      contributing to the progression of intimal hyperplasia.

PMID- 15142848
TI  - Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics
      mechanotransduction in vascular endothelium.
AB  - Recently, we showed that neutral sphingomyelinase (N-SMase) is concentrated at
      the endothelial cell surface in caveolae and is activated to produce ceramide in
      an acute and transient manner by increase in flow rate and pressure in rat lung
      vasculature (Czarny M, Liu J, Oh P, and Schnitzer JE, J Biol Chem 278: 4424-4430,
      2003). Here, we report further on our investigations of this new acute
      mechanotransduction pathway. We employed three experimental models to explore the
      role of N-SMase and ceramides in mechanosignaling: 1) a cell-free, in vitro model
      using isolated luminal plasma membranes of rat lung endothelium; 2) a fluid shear
      stress model using monolayers of intact bovine aorta endothelial cell in culture;
      and 3) an in situ model using controlled perfusion of the rat lung vasculature.
      Scyphostatin, which specifically inhibited N-SMase but not acid SMase activity,
      prevented mechanoactivation of N-SMase as well as downstream tyrosine and mitogen
      activated protein kinases. Cell-permeable ceramide analogs (N-acetylsphingosine,
      C2-ceramide, and N-hexanoylsphingosine, C6-ceramide) but not the inactive
      dihydroderivatives D2-ceramide and D6-ceramide (N-acetylsphinganine and N
      hexanoylsphinganine, respectively) mimic rapid mechano-induced tyrosine
      phosphorylation of cell surface proteins as well as mechanoactivation of Src-like
      kinases and the extracellular regulated kinase pathway. The responses common to
      ceramide and mechanical stress were inhibited by genistein, herbamycin A, and
      PP2, but not PP3, which suggests an obligate role of Src-like kinases in ceramide
      mediated mechanotransduction. Ceramides also induced serine/threonine
      phosphorylation to activate the Akt/endothelial nitric oxide synthase pathway.
      Thus N-SMase at the plasma membrane in caveolae may be an upstream initiating
      mechanosensor, which acutely triggers mechanotransduction by generation of the
      lipid second messenger ceramide.

PMID- 15142850
TI  - Myocardial O2 consumption in porcine left ventricle is heterogeneously
      distributed in parallel to heterogeneous O2 delivery.
AB  - Myocardial blood flow is unevenly distributed, but the cause of this
      heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of
      oxygen demand. The aim of the present study was to assess the relation between
      oxygen consumption and blood flow in small tissue regions in porcine left
      ventricle. In seven male, anesthetized, open-chest pigs, local oxygen consumption
      was quantitated by computational model analysis of the incorporation of 13C in
      glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate
      into the left anterior descending coronary artery. Blood flow was measured with
      radioactive microspheres before and during acetate infusion. High-resolution
      nuclear magnetic resonance 13C spectra were obtained from extracts of tissue
      samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean
      regional myocardial blood flow was stable [5.0 +/- 1.6 (SD) and 5.0 +/- 1.4
      ml.min(-1).g dry wt(-1) before and after 30 min of acetate infusion,
      respectively]. Mean left ventricular oxygen consumption measured with the NMR
      method was 18.6 +/- 7.7 micromol.min(-1).g dry wt(-1) and correlated well (r =
      0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow,
      hemoglobin, and blood gas measurements (mean 22.8 +/- 4.7 micromol.min(-1).g dry
      wt(-1)). Local blood flow and oxygen consumption were significantly correlated (r
      = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the
      heart at normal workload, the variance of left ventricular oxygen delivery at
      submilliliter resolution is explained for 43% by heterogeneity in oxygen demand.

PMID- 15142851
TI  - Plasma volume expansion does not increase maximal cardiac output or VO2 max in
      lowlanders acclimatized to altitude.
AB  - With altitude acclimatization, blood hemoglobin concentration increases while
      plasma volume (PV) and maximal cardiac output (Qmax) decrease. This investigation
      aimed to determine whether reduction of Qmax at altitude is due to low
      circulating blood volume (BV). Eight Danish lowlanders (3 females, 5 males: age
      24.0 +/- 0.6 yr; mean +/- SE) performed submaximal and maximal exercise on a
      cycle ergometer after 9 wk at 5,260 m altitude (Mt. Chacaltaya, Bolivia). This
      was done first with BV resulting from acclimatization (BV = 5.40 +/- 0.39 liters)
      and again 2-4 days later, 1 h after PV expansion with 1 liter of 6% dextran 70
      (BV = 6.32 +/- 0.34 liters). PV expansion had no effect on Qmax, maximal O2
      consumption (VO2), and exercise capacity. Despite maximal systemic O2 transport
      being reduced 19% due to hemodilution after PV expansion, whole body VO2 was
      maintained by greater systemic O2 extraction (P < 0.05). Leg blood flow was
      elevated (P < 0.05) in hypervolemic conditions, which compensated for
      hemodilution resulting in similar leg O2 delivery and leg VO2 during exercise
      regardless of PV. Pulmonary ventilation, gas exchange, and acid-base balance were
      essentially unaffected by PV expansion. Sea level Qmax and exercise capacity were
      restored with hyperoxia at altitude independently of BV. Low BV is not a primary
      cause for reduction of Qmax at altitude when acclimatized. Furthermore,
      hemodilution caused by PV expansion at altitude is compensated for by increased
      systemic O2 extraction with similar peak muscular O2 delivery, such that maximal
      exercise capacity is unaffected.

PMID- 15142852
TI  - Oxygen-dependent and tissue-specific regulation of erythropoietin gene
      expression.
AB  - Hypoxia-inducible expression of the gene encoding for the glycoprotein hormone
      erythropoietin (EPO) is the paradigm of oxygen-regulated gene expression. EPO is
      the main regulator of red blood cell production and more than 100 years of
      research on the regulation of EPO production have led to the identification of a
      widespread cellular oxygen sensing mechanism. Central to this signaling cascade
      is the transcription factor complex hypoxia-inducible factor-1 (HIF-1).
      Meanwhile, it is known that HIF-1 controls more than 50 oxygen-dependent genes
      and is now recognized as the main regulator of oxygen homoeostasis in the body.
      In addition to hypoxic induction, expression of the EPO gene is tightly regulated
      in a tissue-specific manner. During ontogeny, production of EPO required for
      erythropoiesis is switched from the fetal liver to the kidneys. Here EPO is
      mainly synthesized in adulthood. Production of EPO has also been found in organs
      where it has nonerythropoietic functions: EPO is important for development of the
      brain and is neuroprotective, whereas it stimulates angiogenesis in the
      reproductive tract and possibly in other organs. Understanding oxygen and tissue
      specific regulation of EPO production is of high relevance for physiology.
      Moreover, this knowledge might be useful for new therapies to treat human
      diseases.

PMID- 15142853
TI  - Inflammatory cytokines, vascular function, and hypertension.

PMID- 15142854
TI  - Increased food intake and CCK receptor antagonists: beyond abdominal vagal
      afferents.

PMID- 15142855
TI  - A mechanism underlying mature-onset obesity: evidence from the hyperphagic
      phenotype of brain-derived neurotrophic factor mutants.
AB  - Mice deficient in brain-derived neurotrophic factor (BDNF) develop mature-onset
      obesity, primarily due to overeating. To gain insight into the mechanism of this
      hyperphagia, we characterized food intake, body weight, meal pattern, and meal
      microstructure in young and mature mice fed balanced or high-fat diets.
      Hyperphagia and obesity occurred in mature but not young BDNF mutants fed a
      balanced diet. This hyperphagia was mediated by increased meal number, which was
      associated with normal meal size, meal duration, and satiety ratio. In contrast,
      the high-fat diet induced premature development of hyperphagia and obesity in
      young BDNF mutants and a similar magnitude hyperphagia in mature mutants. This
      hyperphagia was supported by increased meal size and was accompanied by a reduced
      satiety ratio. Thus the mechanism underlying hyperphagia was present before
      significant weight gain, but whether it occurred, and whether meal frequency or
      meal size was altered to support it, was modulated by a process associated with
      aging and by diet properties. Meal pattern changes associated with the balanced
      diet suggested meal initiation, and the oropharyngeal positive feedback that
      drives feeding, were enhanced and might have contributed to overeating in BDNF
      mutants, whereas negative feedback was normal. Consistent with this hypothesis,
      meal microstructure revealed that all hyperphagic mutant groups exhibited
      increased intake rates at meal onset. Therefore, the central nervous system
      targets of BDNF actions may include orosensory brain stem neurons that process
      and transmit positive feedback or forebrain neurons that modulate its strength.

PMID- 15142857
TI  - Sympathetic innervation of white adipose tissue and its regulation of fat cell
      number.
AB  - White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS),
      and the central origins of this innervation have been demonstrated for inguinal
      and epididymal WAT (iWAT and eWAT, respectively) using a viral transneuronal
      tract tracer, the pseudorabies virus (PRV). Although the more established role of
      this sympathetic innervation of WAT is as a major stimulator of lipid
      mobilization, this innervation also inhibits WAT fat cell number (FCN); thus,
      local denervation of WAT leads to marked increases in WAT mass and FCN. The
      purpose of this study was to extend our understanding of the SNS regulation of
      FCN using neuroanatomical and functional analyses. Therefore, we injected PRV
      into retroperitoneal WAT (rWAT) to compare the SNS outflow to this pad from what
      already is known for iWAT and eWAT. In addition, we tested the ability of local
      unilateral denervation of rWAT or iWAT to promote increases in WAT mass and FCN
      vs. their contralateral neurally intact counterparts. Although the overall
      pattern of innervation was more similar than different for rWAT vs. iWAT or eWAT,
      its SNS outflow appeared to involve more neurons in the suprachiasmatic and
      solitary tract nuclei. Denervation produced significant increases in WAT mass and
      FCN for both iWAT and rWAT, but FCN was increased significantly more in iWAT than
      in rWAT. These data suggest differences in origins of the sympathetic outflow to
      WAT and functional differences in the WAT SNS innervation that could contribute
      to the differential propensity for fat cell proliferation across WAT depots in
      vivo.

PMID- 15142856
TI  - Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and
      enhances contraction in systemic vessels of pregnant rats.
AB  - IL-6 is elevated in plasma of preeclamptic women, and twofold elevation of plasma
      IL-6 increases vascular resistance and arterial pressure in pregnant rats,
      suggesting a role of the cytokine in hypertension of pregnancy. However, whether
      the hemodynamic effects of IL-6 reflect direct effects of the cytokine on the
      mechanisms of vascular contraction/relaxation is unclear. The purpose of this
      study was to test the hypothesis that IL-6 directly impairs endothelium-dependent
      relaxation and enhances vascular contraction in systemic vessels of pregnant
      rats. Active stress was measured in aortic strips isolated from virgin and late
      pregnant Sprague-Dawley rats and then nontreated or treated for 1 h with IL-6 (10
      pg/ml to 10 ng/ml). In endothelium-intact vascular strips, phenylephrine (Phe,
      10(-5) M) caused an increase in active stress that was smaller in pregnant (4.2
      +/- 0.3) than virgin rats (5.1 +/- 0.3 x 10(4) N/m(2)). IL-6 (1,000 pg/ml) caused
      enhancement of Phe contraction that was greater in pregnant (10.6 +/- 0.7) than
      virgin rats (7.5 +/- 0.4 x 10(4) N/m(2)). ACh and bradykinin caused relaxation of
      Phe contraction and increases in vascular nitrite production that were greater in
      pregnant than virgin rats. IL-6 caused reductions in ACh- and bradykinin-induced
      vascular relaxation and nitrite production that were more prominent in pregnant
      than virgin rats. Incubation of endothelium-intact strips in the presence of
      N(omega)-nitro-L-arginine methyl ester (10(-4) M) to inhibit nitric oxide (NO)
      synthase, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-5) M) to
      inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and
      enhanced Phe-induced stress in nontreated but to a lesser extent in IL-6-treated
      vessels, particularly those of pregnant rats. Removal of the endothelium enhanced
      Phe-induced stress in nontreated but not IL-6-treated vessels, particularly those
      of pregnant rats. In endothelium-denuded strips, relaxation of Phe contraction
      with sodium nitroprusside, an exogenous NO donor, was not different between
      nontreated and IL-6-treated vessels of virgin or pregnant rats. Thus IL-6
      inhibits endothelium-dependent NO-cGMP-mediated relaxation and enhances
      contraction in systemic vessels of virgin and pregnant rats. The greater IL-6
      induced inhibition of vascular relaxation and enhancement of contraction in
      systemic vessels of pregnant rats supports a direct role for IL-6 as one possible
      mediator of the increased vascular resistance associated with hypertension of
      pregnancy.

PMID- 15142858
TI  - Unilateral lower limb suspension can cause deep venous thrombosis.

PMID- 15142859
TI  - Morphologic findings of coronary atherosclerotic plaques in diabetics: a
      postmortem study.
AB  - OBJECTIVE: Coronary atherosclerotic plaque composition of diabetic subjects and
      localization of receptor for advanced glycation end products (RAGE) and its
      ligands have not been extensively studied. METHODS AND RESULTS: Hearts from
      diabetic subjects and age, race, and sex-matched nondiabetic subjects dying
      suddenly were examined. Coronary arteries were dissected and lesions were
      evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The
      expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death
      (apoptosis) were also determined. Lesions from type II diabetic subjects had
      larger mean necrotic cores (P=0.01) and greater total and distal plaque load
      (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively
      with diabetic status, independent of other risk factors. Intimal staining for
      macrophages, T-cells, and HLA-DR was also significantly greater in diabetic
      subjects (P=0.03, P=0.003, and P<0.0001), respectively. The association of
      increased macrophage infiltrate was independent of cholesterol levels and patient
      age. Expression of RAGE and EN-RAGE was significantly greater in diabetic
      subjects (P=0.004) and was associated with apoptotic smooth muscle cells and
      macrophages. CONCLUSIONS: In sudden coronary death, inflammation and necrotic
      core size play a greater role in the progression of atherosclerosis in diabetic
      subjects. The expression of RAGE and EN-RAGE may further compromise cell survival
      and promote plaque destabilization.

PMID- 15142860
TI  - Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue
      factor expression: involvement of myeloperoxidase-mediated oxidant in plaque
      erosion and thrombogenesis.
AB  - OBJECTIVE: Superficial erosion of coronary plaques due to endothelial loss causes
      acute coronary syndromes (ACS). Macrophages at erosive sites of human coronary
      atheroma present myeloperoxidase (MPO), an enzyme that produces hypochlorous acid
      (HOCl). METHODS AND RESULTS: Activated MPO-positive macrophages or exogenous HOCl
      promoted detachment of endothelial cells (EC) from "Matrigel" substrata in vitro.
      Pathophysiologically relevant concentrations of HOCl caused EC death in a
      concentration-dependent manner: HOCl (20 to 50 micromol/L) induced rapid
      shrinkage of EC with nuclear condensation and disruption of EC monolayers,
      whereas concentrations >100 micromol/L immediately induced blebbing of the EC
      plasma membrane without shrinkage. HOCl (30 to 50 micromol/L) also induced
      caspase-3 activation, poly (ADP-ribose) polymerase degradation, and DNA laddering
      in EC. HOCl rapidly decreased endothelial Bcl-2 and induced cytochrome-C release,
      indicating that HOCl activates apoptotic EC death, partially via mitochondrial
      damage. Increased intracellular glutathione (GSH) levels after treatment with GSH
      monoethyl ester (GSH-MEE) attenuated HOCl-induced EC apoptosis. Sublethal
      concentrations of HOCl (1.0 to 15 micromol/L) increased tissue factor in EC and
      GSH-MEE treatment limited this effect of HOCl. CONCLUSIONS: HOCl can provoke EC
      death and desquamation by either apoptotic or oncotic cell-death pathways, and
      sublethal concentrations of HOCl can increase endothelial tissue factor. These
      results show that MPO-positive macrophage-derived HOCl in the subendothelium of
      atheromata may participate in ACS by promoting superficial erosion and increasing
      thrombogenicity.

PMID- 15142861
TI  - Microtubules regulate angiotensin II type 1 receptor and Rac1 localization in
      caveolae/lipid rafts: role in redox signaling.
AB  - OBJECTIVE: Microtubules are important in signal transduction temporal-spatial
      organization. Full expression of angiotensin II (Ang II) signaling in vascular
      smooth muscle cells (VSMCs) is dependent on the reactive oxygen species (ROS)
      derived from nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase and
      the dynamic association of the Ang II type 1 receptor (AT1R) with caveolae/lipid
      rafts. Translocation of the small GTPase Rac1 to the plasma membrane is an
      essential step for activation of NAD(P)H oxidase; however, its precise
      localization in the plasma membrane after agonist stimulation and how it is
      targeted are unknown. We hypothesized that microtubules are involved in
      regulating multiphasic Ang II signaling events in VSMC. METHODS AND RESULTS: We
      show that Ang II promotes Rac1 and AT1R trafficking into caveolae/lipid rafts,
      which is blocked by disruption of microtubules with nocodazole. As a consequence,
      nocodazole significantly inhibits Ang II-stimulated H2O2 production, its
      downstream ROS-dependent epidermal growth factor receptor transactivation, Akt
      phosphorylation, and vascular hypertrophy without affecting Rac1 activation or
      ROS-independent extracellular signal-regulated kinase 1/2 phosphorylation.
      CONCLUSIONS: These results suggest that proper Rac1 and AT1R trafficking into
      caveolae/lipid rafts requires the integrity of microtubules and provide insight
      into the essential role of microtubules for the spatial-temporal organization of
      ROS-dependent and caveolae/lipid rafts-dependent AT(1)R signaling linked to
      vascular hypertrophy.

PMID- 15142862
TI  - Atherosclerotic plaque smooth muscle cells have a distinct phenotype.
AB  - OBJECTIVE: The present study addresses the question, "Are plaque smooth muscles
      cells (SMCs) genetically distinct from medial SMCs as reflected by the ability to
      maintain a distinctive expression phenotype in vitro?" METHODS AND RESULTS:
      Multiple cell strains were developed from carotid endarcterectomy specimens, and
      quadruplicate array hybridizations were completed for each sample. A new
      normalization protocol was developed and used to analyze the data. Permutation
      analysis suggests that most of the significant differences in expression could
      not have occurred by chance. A broad pattern of significant expression
      differences, consisting of almost 5% of the genes probed, was detected.
      Quantitative polymerase chain reaction (QPCR) confirmation was found in 70% of a
      subset of genes selected for validation. CONCLUSIONS: The SMC cultures were
      nearly indistinguishable by morphological features, population doubling time, and
      sensitivity to cell death induced by Fas cross-linking. Surprisingly, array
      expression analysis identified differences so extensive that we conclude that
      plaque and medial SMCs are distinctly different SMC cell types.

PMID- 15142863
TI  - Protein C levels are regulated by a quantitative trait locus on chromosome 16:
      results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project.
AB  - OBJECTIVE: Protein C (PC) is a component of the protein C anticoagulant pathway.
      PC deficiency is a risk factor associated with venous thromboembolism. As part of
      the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project, we conducted a
      genome-wide linkage scan to localize genes that influence variation in PC plasma
      levels. METHODS AND RESULTS: PC levels were measured in 398 individuals belonging
      to 21 Spanish families. A total of 485 DNA microsatellite markers were genotyped
      to provide a 7.1-cM genetic map. Variance component linkage methods were used to
      evaluate linkage and to detect quantitative trait loci (QTL). A region on
      chromosome 16 (16q23), flanked by markers D16S3106 and D16S516, showed strong
      evidence of linkage with PC levels (LOD=3.69). This region contains 1 positional
      candidate gene, the NAD(P)H:dehydrogenase quinone 1 (NQO1), involved in vitamin K
      metabolism. The association of 1 SNP of this gene with PC levels (P=0.005)
      strongly supports the implication of NQO1 gene in the variability of PC levels.
      CONCLUSIONS: These results illustrate the application of genomic scans to
      identify the genetic determinants of quantitative variation in a component of the
      hemostatic pathways. They provide strong evidence for a locus (QTL) on chromosome
      16 that influences PC levels.

PMID- 15142864
TI  - Effect of pravastatin on low-density lipoprotein oxidation and myocardial
      perfusion in young adults with type 1 diabetes.
AB  - OBJECTIVE: Diabetes has been associated with increased oxidative stress and
      impaired vascular function. Statins have been shown to reduce low-density
      lipoprotein (LDL) oxidizability and improve myocardial perfusion in
      hypercholesterolemic nondiabetic subjects. We studied whether pravastatin
      decreases LDL oxidation and improves myocardial perfusion in normocholesterolemic
      subjects with type 1 diabetes. METHODS AND RESULTS: In this randomized, double
      blind study, myocardial perfusion was measured at rest and during dipyridamole
      stimulation with positron emission tomography and [15O]H2O during
      hyperinsulinemic euglycemia in 42 patients (age 30+/-6 years; LDL cholesterol
      2.48+/-0.57 mmol/L) before and after 4-month treatment with pravastatin 40 mg/d
      or placebo. In addition, 12 healthy nondiabetic subjects were studied. LDL
      oxidation was measured by determining the level of baseline diene conjugation in
      lipids extracted from LDL. The level of LDL oxidation was similar in the
      pravastatin and placebo groups before treatment (23.9+/-4.6 versus 25.6+/-9.5
      micromol/L, respectively) and decreased significantly during pravastatin
      treatment to 19.5+/-5.0 micromol/L (P<0.005). Myocardial perfusion reserve was
      significantly lower in diabetic patients compared with controls (4.15+/-1.29
      versus 5.31+/-1.86, P<0.05) and did not change after treatment. Glycemic control
      and insulin sensitivity remained unchanged during treatment. CONCLUSIONS:
      Pravastatin treatment, resulting in decreased LDL oxidation, did not improve
      myocardial perfusion reserve in subjects with type 1 diabetes.

PMID- 15142865
TI  - A20 inhibits toll-like receptor 2- and 4-mediated interleukin-8 synthesis in
      airway epithelial cells.
AB  - The zinc finger protein A20 is encoded by an immediate early response gene and
      acts as an inhibitor of nuclear factor (NF)-kappaB-dependent gene expression
      induced by different stimuli, including tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta). Toll-like receptor 2 (TLR2) and TLR4 have been
      found to transduce, respectively, peptidoglycan (PGN) and lipopolysaccharide
      (LPS) signals for the activation of NF-kappaB and the production of inflammatory
      cytokines. Here, we have examined the role of A20 in TLR-mediated NF-kappaB
      dependent gene expression in human airway epithelial cells (AECs). Stimulation
      with LPS and PGN resulted in a significant increase in the level of A20 mRNA in
      primary cultured AECs and in NCI-H292 AECs. LPS and PGN induced activation of the
      IL-8 promoter both in NCI-H292 AECs and in HEK293 cells expressing either TLR2 or
      TLR4 plus MD-2. Dominant-negative myeloid differentiation protein and a mutant
      form of IkappaBalpha attenuated this PGN- or LPS-induced activation of the IL-8
      promoter. Furthermore, overexpression of A20 inhibited activation of both NF
      kappaB and the IL-8 promoter by PGN or LPS in these cells. Taken together, our
      results suggest that A20 may function as a negative regulator of TLR-mediated
      inflammatory responses in the airway, thereby protecting the host against harmful
      overresponses to pathogens.

PMID- 15142866
TI  - Occupational screening for obstructive sleep apnea in commercial drivers.
AB  - Excluding the presence of obstructive sleep apnea in commercial drivers is
      valuable, as the syndrome may increase their risk of sleepiness-related
      accidents. Using polysomnography as the criterion standard, we prospectively
      compared accuracies of five strategies in excluding the presence of severe sleep
      apnea and, secondarily, any sleep apnea among 406 commercial drivers. These
      strategies were as follows: (1) symptoms; (2) body mass index; (3) symptoms plus
      body mass index; (4) a two-stage approach with symptoms plus body mass index for
      everyone, followed by oximetry for a subset; and (5) oximetry for all. For
      excluding severe apnea, the two-stage strategy was highly successful, with 91%
      sensitivity and specificity, and a negative likelihood ratio of 0.10. This
      strategy was comparable in accuracy to oximetry, which had a negative likelihood
      ratio of 0.12, and was 88% sensitive and 95% specific. If we avoided oximetry
      altogether, then symptoms together with body mass index were 81% sensitive and
      73% specific, with a negative likelihood ratio of 0.26. On the other hand,
      excluding any apnea could not be done with reasonable accuracy unless oximetry
      was used. We conclude that two-stage screening is likely to be a viable means of
      excluding severe sleep apnea among commercial drivers.

PMID- 15142867
TI  - Inhaled carbon monoxide confers antiinflammatory effects against ventilator
      induced lung injury.
AB  - Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality
      in intensive care units. The stress-inducible gene product, heme oxygenase-1, and
      carbon monoxide (CO), a major by-product of heme oxygenase catalysis of heme,
      have been shown to confer potent antiinflammatory effects in models of tissue and
      cellular injury. In this study, we observed increased expression of heme
      oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic
      function of heme oxygenase-1 induction in VILI, we determined whether low
      concentration of inhaled CO could serve to protect the lung against VILI. Low
      concentration of inhaled CO significantly reduced tumor necrosis factor-alpha
      levels and total cell count in lavage fluid, while simultaneously elevating
      levels of antiinflammatory interleukin-10 levels. To better characterize the
      mechanism of CO-mediated antiinflammatory effects, we examined key signaling
      pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate
      that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen
      activated protein kinase pathway but independent of activator protein-1 and
      nuclear factor-kappaB pathways. Our data lead to a tempting speculation that
      inhaled CO might be useful in minimizing VILI.

PMID- 15142868
TI  - Early life environmental control: effect on symptoms, sensitization, and lung
      function at age 3 years.
AB  - We investigated whether environmental control during pregnancy and early life
      affects sensitization and lung function at the age of 3 years. High-risk children
      (n = 251) were prenatally randomized to stringent environmental control (active)
      or no intervention (control). Questionnaires, skin testing, IgE, and specific
      airway resistance (sRaw) measurement were completed at the age of 3 years.
      Children in the active group were significantly more frequently sensitized
      compared with control subjects (at least one allergen by skin tests: risk ratio,
      1.61; 95% confidence interval [CI], 1.02-2.55; p = 0.04; mite by IgE: risk ratio,
      2.85; 95% CI, 1.02-7.97; p = 0.05). However, sRaw was significantly better in the
      active group (kiloPascal/second, geometric mean [95% CI]: 1.05 [1.01-1.10] vs.
      1.19 [1.13-1.25], p < 0.0001, active vs. control). Maximal flow at functional
      residual capacity was measured using rapid thoracic compression at the age of 4
      weeks in a subgroup. Prospective lung function data (at infancy and 3 years) were
      obtained in 32 children (14 active and 18 control). There was no difference in
      infant lung function between the groups, but at 3 years, sRaw was significantly
      lower in the active compared with control children (p = 0.003). Stringent
      environmental control was associated with increased risk of mite sensitization
      but better results for some measurements of lung function in high-risk children
      at the age of 3 years.

PMID- 15142869
TI  - Ambient air pollution and oxygen saturation.
AB  - We investigated the association between fine particulate air pollution and oxygen
      saturation as measured with a peripheral oxygen saturation monitor during a 12
      week repeated-measures study of 28 older Boston residents. Oxygen saturation and
      air pollution particulates with a mean diameter less than or equal to 2.5 microm
      were measured continuously during a protocol of rest, standing, exercise,
      postexercise rest, and 20 cycles of slow, paced breathing. In fixed-effect
      models, mean pollution concentration was associated with reduced oxygen
      saturation during the baseline rest period (6 hours: mean, -0.173%; 95%
      confidence interval [CI], -0.345 to -0.001), postexercise (6 hours: mean, 
      0.173%; 95% CI, -0.332 to -0.014), with a trend toward decrease during
      postexercise paced breathing (6 hours: mean, -0.142%; 95% CI, -0.292 to 0.007)
      but not during exercise. Participants taking beta-blockers had a greater
      pollution-related decrease in oxygen saturation at rest (6 hours: mean, -0.769%;
      95% CI, -1.210 to -0.327) (interaction for particulates with a mean diameter less
      than or equal to 2.5 microm by beta-blocker, p < 0.0005) than did those not
      taking beta-blockers (p > 0.25). The reduction in oxygen saturation associated
      with air pollution may result from subtle particulate-related pulmonary vascular
      and/or inflammatory changes. Further investigation may contribute to our
      understanding of the mechanisms through which particulates may increase
      respiratory and cardiac morbidity among vulnerable populations.

PMID- 15142870
TI  - Future directions in sarcoidosis research: summary of an NHLBI working group.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology that
      primarily affects the lungs. The etiology remains unclear; however,
      environmental, genetic, ethnic, and familial factors probably modify expression
      of the disease. As an example, African Americans are at greater risk of mortality
      and morbidity than are white Americans, and more often have a family history of
      sarcoidosis. Most patients with sarcoidosis recover spontaneously, but some
      develop chronic, debilitating disease. Corticosteroids and other drugs, although
      effective at controlling disease activity, may not influence the overall course
      of disease. Because of the many uncertainties about the pathogenesis, course, and
      management of sarcoidosis, the National Heart, Lung, and Blood Institute convened
      a working group to identify future research directions and opportunities for
      sarcoidosis. These include developing a tissue bank, using novel methods to
      identify genetic factors, studying the immunopathogenesis with human tissue and
      animal models, exploring new approaches to diagnose and manage disease, and,
      finally, conducting randomized controlled trials to assess new therapies.

PMID- 15142871
TI  - Randomized trials describing lung inflammation after pleurodesis with talc of
      varying particle size.
AB  - We report two trials describing whether talc pleurodesis with a mean particle
      size of less than 15 microm ("mixed" talc) produces more lung and systemic
      inflammation than tetracycline or "graded" talc (most particles < 10 microm were
      removed). First, 20 patients with malignant effusions received tetracycline or
      mixed talc. Changes in lung and systemic inflammation from lung clearance scans,
      oxygen saturations, and C-reactive protein from baseline to 48 hours after
      pleurodesis were recorded. Lung inflammation (change in isotope clearance, talc 
      9.26, SD 14.3 vs. tetracycline 4.10, SD 13.8 minutes; difference = -13.4; 95%
      confidence interval [CI], -26.6 to -0.2; p = 0.05) and systemic inflammation
      (change in C-reactive protein, talc 198 SD 79.2 vs. tetracycline 74 SD 79.4
      microg/L; difference = 124; 95% CI, 50 to 199; p = 0.004) were greater after
      talc. Second, 48 patients received mixed or graded talc, and gas exchange was
      assessed from changes in the alveolar-arterial oxygen gradient. Mixed talc
      worsened gas exchange (oxygen gradient change, mixed 2.17 SD 1.74 kPa, 16.3 13.1
      mm Hg vs. graded 0.72 SD 2.46 kPa 5.4 18.5 mm Hg, difference = 1.45; 95% CI, 0.2
      to 2.7; p = 0.03) and induced more systemic inflammation than graded talc. We
      conclude that the routine use of graded talc for pleurodesis would reduce the
      morbidity of this procedure.

PMID- 15142873
TI  - Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell
      transplantation.
AB  - The study of hematopoiesis has been greatly facilitated by transplantation of
      blood cell populations into recipient animals. Efficient engraftment of donor
      cells generally requires ablation of the host hematopoietic system. The zebrafish
      has recently emerged as a developmental and genetic system to study
      hematopoiesis. To enable the study of hematopoietic stem cell (HSC) biology,
      immune cell function, and leukemogenesis in zebrafish, we have developed
      hematopoietic cell transplantation (HCT) into adult recipient animals conditioned
      by gamma irradiation. Dose-response experiments showed that the minimum lethal
      dose (MLD) of 40 Gy led to the specific ablation of hematolymphoid cells and
      death by 14 days after irradiation. Sublethal irradiation doses of 20 Gy
      predominantly ablated lymphocytes and permitted transplantation of a lethal T
      cell leukemia. Finally, transplantation of hematopoietic cells carrying
      transgenes yielding red fluorescent erythrocytes and green fluorescent leukocytes
      showed that HCT is sufficient to rescue the MLD, that recipient hematolymphoid
      tissues were repopulated by donor-derived cells, and that donor blood cell
      lineages can be independently visualized in living recipients. Together, these
      results establish transplantation assays to test for HSC function and oncogenic
      transformation in zebrafish.

PMID- 15142872
TI  - Role of G protein-gated inwardly rectifying potassium channels in P2Y12 receptor
      mediated platelet functional responses.
AB  - The role of the G(i)-coupled platelet P2Y(12) receptor in platelet function has
      been well established. However, the functional effector or effectors contributing
      directly to alphaIIbbeta3 activation in human platelets has not been delineated.
      As the P2Y(12) receptor has been shown to activate G protein-gated, inwardly
      rectifying potassium (GIRK) channels, we investigated whether GIRK channels
      mediate any of the functional responses of the platelet P2Y(12) receptor. Western
      blot analysis revealed that platelets express GIRK1, GIRK2, and GIRK4. In aspirin
      treated and washed human platelets, 2 structurally distinct GIRK inhibitors,
      SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine hydrochloride) and U50488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2
      (pyrrolidinyl)cyclohexyl] benzeneacetamide methanesulfonate), inhibited adenosine
      diphosphate (ADP)-, 2-methylthioADP (2-MeSADP)-, U46619-, and low-dose thrombin
      mediated platelet aggregation. However, the GIRK channel inhibitors did not
      affect platelet aggregation induced by high concentrations of thrombin, AYPGKF,
      or convulxin. Furthermore, the GIRK channel inhibitors reversed SFLLRN-induced
      platelet aggregation, inhibited the P2Y(12)-mediated potentiation of dense
      granule secretion and Akt phosphorylation, and did not affect the agonist-induced
      G(q)-mediated platelet shape change and intracellular calcium mobilization.
      Unlike AR-C 69931MX, a P2Y(12) receptor-selective antagonist, the GIRK channel
      blockers did not affect the ADP-induced adenlylyl cyclase inhibition, indicating
      that they do not directly antagonize the P2Y(12) receptor. We conclude that GIRK
      channels are important functional effectors of the P2Y(12) receptor in human
      platelets.

PMID- 15142874
TI  - Sustained correction of B-cell development and function in a murine model of X
      linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer.
AB  - X-linked agammaglobulinemia (XLA) is a human immunodeficiency caused by mutations
      in Bruton tyrosine kinase (Btk) and characterized by an arrest in early B-cell
      development, near absence of serum immunoglobulin, and recurrent bacterial
      infections. Using Btk- and Tec-deficient mice (BtkTec(-/-)) as a model for XLA,
      we determined if Btk gene therapy could correct this disorder. Bone marrow (BM)
      from 5-fluorouracil (5FU)-treated BtkTec(-/-) mice was transduced with a
      retroviral vector expressing human Btk and transplanted into BtkTec(-/-)
      recipients. Mice engrafted with transduced hematopoietic cells exhibited rescue
      of both primary and peripheral B-lineage development, recovery of peritoneal B1 B
      cells, and correction of serum immunoglobulin M (IgM) and IgG(3) levels. Gene
      transfer also restored T-independent type II immune responses, and B-cell antigen
      receptor (BCR) proliferative responses. B-cell progenitors derived from Btk
      transduced stem cells exhibited higher levels of Btk expression than non-B cells;
      and marking studies demonstrated a selective advantage for Btk-transduced B
      lineage cells. BM derived from primary recipients also rescued Btk-dependent
      function in secondary hosts that had received a transplant. Together, these data
      demonstrate that gene transfer into hematopoietic stem cells can reconstitute Btk
      dependent B-cell development and function in vivo, and strongly support the
      feasibility of pursuing Btk gene transfer for XLA.

PMID- 15142875
TI  - Glutathione S-transferase M1 polymorphism: a risk factor for hepatic
      venoocclusive disease in bone marrow transplantation.
AB  - Hepatic venoocclusive disease (HVOD) in bone marrow transplantation (BMT) is
      attributed to toxicity of cytoreductive agents, especially busulfan and
      cyclophosphamide, in the conditioning therapy. Busulfan, as well as the
      metabolites of cyclophosphamide, are conjugated with glutathione (GSH), catalyzed
      by enzymes of the glutathione S-transferase (GST) family. To assess the impact of
      polymorphisms of the GST genes, GSTM1 and GSTT1, on the risk of HVOD, we
      evaluated 114 consecutive patients with beta-thalassemia major undergoing BMT.
      There was a significantly increased incidence of HVOD in patients with the GSTM1
      null genotype compared with those with the GSTM1-positive genotype (46.5% vs
      18.3%; P =.001). Pharmacokinetic analysis in these patients showed that the
      clearance of busulfan was higher and first-dose steady-state concentration was
      lower among those with HVOD (0.403 +/- 0.06 vs 0.33 +/- 0.071 L/h/kg, Student t
      test P value =.000 01; and 508 +/- 125 vs 656 +/- 255 ng/mL, t test P value
      =.001, respectively). We conclude that the GSTM1-null genotype predisposes to
      HVOD, and the sinusoidal endothelial cells and hepatocyte damage may be mediated
      by metabolites of busulfan through depletion of the cellular GSH pool.

PMID- 15142876
TI  - Mutations of AML1 are common in therapy-related myelodysplasia following therapy
      with alkylating agents and are significantly associated with deletion or loss of
      chromosome arm 7q and with subsequent leukemic transformation.
AB  - The AML1 transcription factor is essential for normal hematopoiesis and is the
      target of several chromosomal translocations in acute leukemia. Acquired somatic
      AML1 mutations were recently demonstrated sporadically in de novo myelodysplasia
      (MDS) and acute myeloid leukemia (AML) including a few cases of therapy-related
      disease (t-MDS/t-AML). We examined 140 patients with t-MDS or t-AML for AML1
      mutations by direct sequencing. We identified 9 missense, 3 nonsense, and 10
      frameshift mutations, all heterozygous, in 22 patients (15.7%). Thirteen
      mutations were located in the N-terminal Runt homology domain (RHD), whereas 9
      mutations were located in the C-terminal region including the transactivation
      domain (TAD). Nineteen patients with AML1 mutations had previously received
      alkylating agents whereas 2 patients had received radiotherapy only. AML1
      mutations were highly significantly associated with presentation of the disease
      as t-MDS (P =.003), with deletion or loss of chromosome arm 7q (P =.001) and with
      subsequent transformation to overt t-AML (P =.0001). Patients with missense
      mutations presented a shorter survival compared with patients with
      nonsense/frameshift mutations (P =.03). Our results suggest that AML1 mutations
      and deletion of genes on chromosome arm 7q cooperate in leukemogenesis and
      predispose to leukemic transformation.

PMID- 15142877
TI  - Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome
      family.
AB  - We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome
      (WAS) who experienced progressive clinical improvement and revertant T-cell
      mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to
      have occurred by DNA polymerase slippage. We now describe 2 additional patients
      from the same family who also had revertant T lymphocytes that showed selective
      in vivo advantage. Somatic mosaicism was demonstrated on leukocytes cryopreserved
      in the first patient when he was 22 years old, 11 years before his death from
      kidney failure. The second patient is now 16 years old, has a moderate clinical
      phenotype, and developed revertant cells after the age of 14 years. These results
      support DNA polymerase slippage as a common underlying mechanism, and they
      indicate that T-cell mosaicism may have different clinical effects in WAS.

PMID- 15142878
TI  - Platelet surface glutathione reductase-like activity.
AB  - We previously found that reduced glutathione (GSH) or a mixture of
      GSH/glutathione disulfide (GSSG) potentiated platelet aggregation. We here report
      that GSSG, when added to platelets alone, also potentiates platelet aggregation.
      Most of the GSSG was converted to GSH by a flavoprotein-dependent platelet
      surface mechanism. This provided an appropriate redox potential for platelet
      activation. The addition of GSSG to platelets generated sulfhydryls in the beta
      subunit of the alpha(IIb)beta(3) fibrinogen receptor, suggesting a mechanism for
      facilitation of agonist-induced platelet activation.

PMID- 15142879
TI  - Erythropoietin gene from a teleost fish, Fugu rubripes.
AB  - In this paper we report the cloning and characterization of the erythropoietin
      (Epo) gene from the pufferfish, Fugu rubripes. This is the first nonmammalian Epo
      gene to be cloned. The Fugu Epo comprises 5 exons and 4 introns similar to the
      human EPO, and encodes a 185-amino acid protein that is 32% to 34% identical to
      Epo from various mammals. The synteny of genes at the Epo locus is conserved
      between the Fugu and humans. Unlike in mammals in which adult kidney is the
      primary Epo-producing organ, the heart is the main Epo-producing organ in adult
      Fugu. In addition to the heart, Fugu Epo is also expressed in the liver and brain
      similar to the human EPO. Interestingly, the transcripts in the Fugu brain are
      generated from a distal promoter and include an alternatively spliced first
      coding exon. No such brain-specific alternative splicing of Epo has been reported
      in mammals so far. Transient transfection studies in a fish hepatoma cell line
      (PLHC-1) and a human hepatoma cell line (HepG2) suggest that although the Fugu
      Epo promoter many not be hypoxia inducible, the gene may be regulated by hypoxia.

PMID- 15142880
TI  - Randomized comparison of double induction and timed-sequential induction to a "3
      + 7" induction in adults with AML: long-term analysis of the Acute Leukemia
      French Association (ALFA) 9000 study.
AB  - Between 1990 and 1996, we conducted a randomized trial in adults with newly
      diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval
      (RFI) after double induction (arm B), timed-sequential induction (arm C), or
      control "3 + 7" induction (arm A). Patients achieving complete remission (CR)
      after induction +/- salvage received the same consolidation chemotherapy, which
      included a dosage stratification according to patient's age (younger or older
      than 50 years). This long-term analysis was performed in 592 patients (arm A/B/C,
      197/198/197 patients). Overall CR rate was 76% without differences between the 3
      arms, even if a salvage course was less frequently needed in arm B. Treatment
      related mortality, either during the induction or the postremission phase, was
      not significantly higher in arms B and C than in arm A. Among the 449 CR
      patients, 250 relapsed (arm A/B/C, 90/87/73 patients) without significant
      differences in RFI in arms B and C versus arm A (P = .39 and .15, by the Gray
      test). However, when analyzing the 345 patients younger than 50, RFI was
      significantly improved in younger patients receiving timed-sequential induction
      (P = .038 by the Gray test), while not in those receiving double induction. Event
      free survival and overall survival were similar in the 3 randomization arms.

PMID- 15142881
TI  - Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes
      involved in purine metabolism and lower de novo purine synthesis.
AB  - Because de novo purine synthesis (DNPS) is a target of widely used antileukemic
      agents (eg, methotrexate, mercaptopurine), we determined the rate of DNPS and the
      expression of genes involved in purine metabolism in different subtypes of acute
      lymphoblastic leukemia (ALL). Among 113 children with newly diagnosed ALL,
      lymphoblasts with the TEL-AML1 translocation had significantly lower DNPS than
      all other genetic subtypes of B-lineage ALL or T-lineage ALL (352 +/- 57 versus
      1001 +/- 31 or versus 1315 +/- 76 fmol/nmol/h, P <.0001). By assessing the
      expression of 82 genes involved in purine metabolism (KEGG pathway database) in
      ALL blasts from 38 patients with B-lineage ALL (14 with TEL-AML1, 24 without), we
      identified 16 genes that were differentially expressed in TEL-AML1-positive and
      TEL-AML1-negative ALL (P <.001, false discovery rate [FDR] = 5%). The pattern of
      expression of these 16 genes discriminated TEL-AML1-positive ALL with a true
      accuracy of 84% in an independent test set (n = 17, confidence interval 70% to
      94%, P <.001). Western blots of selected genes documented corresponding levels of
      the proteins encoded. Differentially expressed genes included HPRT, IMPDH, PAICS,
      and GART, all of which were expressed at a significantly lower level in TEL-AML1
      ALL. These findings have established that TEL-AML1 ALL has significantly lower de
      novo purine synthesis and differential expression of genes involved in purine
      metabolism.

PMID- 15142882
TI  - 17beta-estradiol (E2) modulates cytokine and chemokine expression in human
      monocyte-derived dendritic cells.
AB  - The effects of estrogen on the immune system are still largely unknown. We have
      investigated the effect of 17beta-estradiol (E(2)) on human monocyte-derived
      immature dendritic cells (iDCs). Short-term culture in E(2) had no effect on iDC
      survival or the expression of cell surface markers. However, E(2) treatment
      significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also
      increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E(2)
      significantly increased secretion of the inflammatory chemokines IL-8 and
      monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the
      constitutive chemokines thymus and activation-regulated chemokine (TARC) and
      macrophage-derived chemokine (MDC). However, after E(2) pretreatment the
      lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was
      clearly enhanced. Moreover, mature DCs pretreated with E(2) stimulated T cells
      better than control cells. Finally, we found that E(2) provides an essential
      signal for migration of mature DCs toward CCL19/macrophage inflammatory protein
      3beta (MIP3beta). In summary, E(2) may affect DC regulation of T-cell and B-cell
      responses, as well as help to sustain inflammatory responses. This may explain,
      in part, the reason serum levels of estrogen correlate with the severity of
      certain autoimmune diseases.

PMID- 15142883
TI  - Apoptotic resistance to ionizing radiation in pediatric B-precursor acute
      lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway
      signaling.
AB  - To investigate possible causes of the variable response to treatment in pediatric
      B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel
      therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA
      damage formation to identify tumors with resistance to p53-dependent apoptosis.
      Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of
      p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen
      tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage;
      although 15 of these tumors had normal accumulation of p53 and p21 proteins,
      examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR,
      suggesting increased NF-kappaB prosurvival signaling as the mechanism of
      apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor
      was consistent with such increased NF-kappaB activity. PARP1 inhibition restored
      p53-dependent apoptosis after IR in these leukemias by reducing NF-kappaB DNA
      binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic
      resistance was associated with a TP53 mutation or with defective activation of
      p53. We conclude that increased NF-kappaB prosurvival signaling is a frequent
      mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and
      that PARP1 inhibition may improve the DNA damage response of these leukemias.

PMID- 15142884
TI  - Comparative proteomic analysis of all-trans-retinoic acid treatment reveals
      systematic posttranscriptional control mechanisms in acute promyelocytic
      leukemia.
AB  - All-trans-retinoic acid (ATRA) induces growth inhibition, differentiation, and
      apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL,
      expression of promyelocytic leukemia protein retinoic acid receptor-alpha (PML
      RARalpha) fusion protein, owing to the t(15; 17) reciprocal translocation, leads
      to a block in the promyelocytic stage of differentiation. Here, we studied
      molecular mechanisms involved in ATRA-induced growth inhibition and myeloid cell
      differentiation in APL. By employing comprehensive high-throughput proteomic
      methods of 2-dimensional (2-D) gel electrophoresis and amino acid-coded mass
      tagging coupled with electrospray ionization (ESI) mass spectrometry, we
      systematically identified a total of 59 differentially expressed proteins that
      were consistently modulated in response to ATRA treatment. The data revealed
      significant down-regulation of eukaryotic initiation and elongation factors,
      initiation factor 2 (IF2), eukaryotic initiation factor 4AI (eIF4AI), eIF4G,
      eIF5, eIF6, eukaryotic elongation factor 1A-1 (eEF1A-1), EF-1-delta, eEF1gamma,
      14-3-3epsilon, and 14-3-3zeta/delta (P <.05). The translational inhibitor
      DAP5/p97/NAT1 (death-associated protein 5) and PML isoform-1 were found to be up
      regulated (P <.05). Additionally, the down-regulation of heterogeneous nuclear
      ribonucleoproteins (hnRNPs) C1/C2, UP2, K, and F; small nuclear RNPs (snRNPs) D3
      and E; nucleoprotein tumor potentiating region (TPR); and protein phosphatase 2A
      (PP2A) were found (P <.05); these were found to function in pre-mRNA processing,
      splicing, and export events. Importantly, these proteomic findings were validated
      by Western blot analysis. Our data in comparison with previous cDNA microarray
      studies and our reverse transcription-polymerase chain reaction (RT-PCR)
      experiments demonstrate that broad networks of posttranscriptional suppressive
      pathways are activated during ATRA-induced growth inhibition processes in APL.

PMID- 15142886
TI  - Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol
      estrogen-mediated oxidative DNA damage in cultured human mammary epithelial
      cells.
AB  - Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring phytoalexin
      present in grapes and other foods, has been reported to possess chemopreventive
      effects as revealed by its striking inhibition of diverse cellular events
      associated with tumor initiation, promotion and progression. In our present
      study, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), when treated with the cultured
      human mammary epithelial (MCF-10A) cells, induced the expression of cytochrome
      P450 1A1 (CYP1A1) and 1B1 (CYP1B1) that are responsible for the oxidation of
      17beta-estradiol to produce catechol estrogens. Resveratrol strongly inhibited
      the TCDD-induced aryl hydrocarbon receptor (AhR) DNA binding activity, the
      expression of CYP1A1 and CYP1B1 and their catalytic activities in MCF-10A cells.
      It also reduced the formation of 2-hydroxyestradiol and 4-hydroxyestradiol from
      17beta-estradiol by recombinant human CYP1A1 and CYP1B1, respectively.
      Furthermore, resveratrol significantly attenuated the intracellular reactive
      oxygen species (ROS) formation and oxidative DNA damage as well as the
      cytotoxicity induced by the catechol estrogens. Our data suggest that CYP1A1- and
      CYP1B1-catalyzed catechol estrogen formation might play a key role in TCDD
      induced oxidative damage, and resveratrol can act as a potential chemopreventive
      against dioxin-induced human mammary carcinogenesis by blocking the metabolic
      formation of the catechol estrogens and scavenging the ROS generated during their
      redox cycling.

PMID- 15142885
TI  - Effects of transfusion with red cells filtered to remove leucocytes: randomised
      controlled trial in patients undergoing major surgery.
AB  - OBJECTIVE: To compare postoperative complications in patients undergoing major
      surgery who received non-filtered or filtered red blood cell transfusions.
      DESIGN: Prospective, randomised, double blinded trial. SETTING: 19 hospitals
      throughout the Netherlands (three university; 10 clinical; six general).
      PARTICIPANTS: 1051 evaluable patients: 79 patients with ruptured aneurysm, 412
      patients undergoing elective surgery for aneurysm, and 560 undergoing
      gastrointestinal surgery. INTERVENTIONS: The non-filtered products had the buffy
      coat removed and were plasma reduced. The filtered products had the buffy coat
      removed, were plasma reduced, and filtered before storage to remove leucocytes.
      MAIN OUTCOME MEASURES: Mortality and duration of stay in intensive care.
      Secondary end points were occurrence of multi-organ failure, infections, and
      length of hospital stay. RESULTS: No significant differences were found in
      mortality (odds ratio for filtered v non-filtered 0.80, 95% confidence interval
      0.53 to 1.21) and in mean stay in intensive care (- 0.4 day, - 1.6 to 0.6 day).
      In the filtered group the mean length of hospital stay was 2.4 days shorter (-
      4.8 to 0.0 day; P = 0.050) and the incidence of multi-organ failure was 30% lower
      (odds ratio 0.70, 0.49 to 1.00; P = 0.050). There were no differences in rates of
      infection (0.98, 0.73 to 1.32). CONCLUSION: The use of filtered transfusions in
      some types of major surgery may reduce the length of hospital stay and the
      incidence of postoperative multi-organ failure.

PMID- 15142887
TI  - DNA mismatch repair pathway defects in the pathogenesis and evolution of myeloma.
AB  - Genetic instability is a prominent feature in multiple myeloma and progression of
      this disease from monoclonal gammopathy of uncertain significance (MGUS) and
      smouldering myeloma (SMM) is associated with increasing molecular and chromosomal
      abnormalities. The DNA mismatch repair (MMR) pathway is a post-replicational DNA
      repair system that maintains genetic stability by repairing mismatched bases and
      insertion/deletion loops mistakenly incorporated during DNA replication.
      Deficiencies in proteins pivotal to this pathway result in a higher mutation
      rate, particularly at regions of microsatellite DNA. We have investigated the
      proficiency of the MMR pathway in clinical samples and myeloma cell lines.
      Microsatellite analysis showed instability at one or more of nine loci examined
      in 15 from 92 patients: 7.7% of MGUS/SMM, 20.7% of MM/plasma cell leukaemia (PCL)
      and 12.5% of relapsed MM/PCL. An in vitro heteroduplex G/T repair assay found
      reduced repair in two cell lines, JIM1 and JIM3, and in two of four PCL cases and
      was associated with aberrant expression of at least one mismatch repair protein.
      Thus we show that MMR defects are found in plasma cell dyscrasias and the
      increased frequency during more active stages of the disease suggests a
      contributory role in disease progression.

PMID- 15142888
TI  - Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription
      from the DR5 gene promoter through Sp1 sites in colon cancer cells.
AB  - Sodium butyrate, a short-chain fatty acid naturally present in the human colon,
      is able to induce cell cycle arrest, differentiation and apoptosis in various
      cancer cells. Sodium butyrate is most probably related to the inhibition of
      deacetylases leading to hyperacetylation of chromatin components such as histones
      and non-histone proteins and to alterations in gene expression. In this study, we
      demonstrate for the first time that sodium butyrate selectively up-regulated DR5
      but had no effect on the expression of the other TNF-alpha-related apoptosis
      inducing ligand (TRAIL) receptor, DR4. Sodium butyrate-induced expression of DR5
      involves the putative Sp1 site within the DR5 promoter region. Using a
      combination of the electrophoretic mobility shift assay and the luciferase
      reporter assay, we found that a specific Sp1 site (located at -195 bp relative to
      the transcription start site) is required for sodium butyrate-mediated activation
      of the DR5 promoter. When HCT116 cells were incubated with sodium butyrate and
      TRAIL, enhanced TRAIL-mediated apoptosis was observed. The enhanced apoptosis was
      measured by fluorescent activated cell sorting analysis, DNA fragmentation, poly
      (ADP-ribose) polymerase cleavage, down-regulation of XIAP and caspase activity.
      Taken together, the present studies suggest that sodium butyrate may be an
      effective sensitizer of TRAIL-induced apoptosis.

PMID- 15142890
TI  - What next for electronic communication and health care?

PMID- 15142889
TI  - Carcinogenicity of aminophenylnorharman, a possible novel endogenous mutagen,
      formed from norharman and aniline, in F344 rats.
AB  - A novel mutagenic compound, 9-(4'-aminophenyl)-9H- pyrido[3,4-b]indole
      (aminophenylnorharman, APNH), is shown to be formed by the in vitro enzymatic
      reaction of 9H-pyrido[3,4-b]indole (norharman) and aniline. APNH generates DNA
      adducts (dG-C8-APNH), and is potently genotoxic to bacteria and mammalian cells.
      APNH has also been demonstrated to be formed in vivo from norharman and aniline,
      and suggested to be a new type of endogenous mutagenic compound. To determine its
      carcinogenic activity, long-term administration of APNH was investigated in 93
      male and 90 female F344 rats. Rats were fed diets containing 0, 20 or 40 p.p.m.
      from 7 weeks of age. All animals were killed after 85 weeks treatment and
      necropsy was performed. Hepatocellular carcinomas (HCCs) were induced at
      incidences of 10 and 79% in male rats fed 20 and 40 p.p.m. APNH, and 34% in
      female rats fed 40 p.p.m. of APNH, respectively. In addition, colon
      adenocarcinomas were found at incidences of 3 and 9% in male rats, and 4 and 13%
      in female rats fed 20 and 40 p.p.m. of APNH, respectively. Other tumors,
      including thyroid carcinomas and mononuclear cell leukemia, were also seen in
      rats fed APNH. Polymerase chain reaction-single strand conformation polymorphism
      analysis revealed beta-catenin gene mutations in 24% of HCCs and K-ras, beta
      catenin and Apc gene mutations were found in 22, 44 and 33% of colon cancers
      induced by APNH, respectively. Most mutations occurred at G:C base pairs. beta
      Catenin protein accumulations in the nucleus and cytoplasm were also revealed in
      both liver and colon tumors. Thus, APNH induced liver and colon cancers with K
      ras, beta-catenin and Apc gene mutations in F344 rats.

PMID- 15142891
TI  - National programme for information technology.

PMID- 15142892
TI  - Beyond the gadgets.

PMID- 15142893
TI  - Will e-learning improve clinical judgment?

PMID- 15142894
TI  - The first generation of e-patients.

PMID- 15142895
TI  - Evaluation of ehealth systems and services.

PMID- 15142896
TI  - WHO admits its target on AIDS drugs may be unrealistic.

PMID- 15142897
TI  - Pregnancy and childbirth are leading causes of death in teenage girls in
      developing countries.

PMID- 15142898
TI  - Six health workers sentenced to death in Libya.

PMID- 15142899
TI  - Whistleblower removed from job for talking to the press.

PMID- 15142900
TI  - BMA settles in race discrimination cases.

PMID- 15142901
TI  - Robin Cook warns of threat to aid from war against terrorism.

PMID- 15142902
TI  - Human rights group accuses Russian government of hampering efforts to tackle
      HIV/AIDS.

PMID- 15142903
TI  - Judge finds Governor Bush's law unconstitutional.

PMID- 15142904
TI  - Five cases of child murder to be reopened.

PMID- 15142905
TI  - Electronic prescribing could save at least 29bn dollars.

PMID- 15142907
TI  - EU wants every member to develop a "roadmap" for ehealth.

PMID- 15142909
TI  - Paper prescriptions will soon be distinctly "last season".

PMID- 15142908
TI  - Can the new "electronic highway" for the NHS have a smooth launch?

PMID- 15142910
TI  - GPs worried about having to change to new untested software systems.

PMID- 15142911
TI  - All hospital bookings to be done electronically by end of 2005.

PMID- 15142912
TI  - Experts urge action to stop animal diseases infecting humans.

PMID- 15142916
TI  - Generics industry and doctors nervous over free trade deal.

PMID- 15142917
TI  - The professor of "telepreventive medicine".

PMID- 15142919
TI  - Patients' experience with a diabetes support programme based on an interactive
      electronic medical record: qualitative study.
AB  - OBJECTIVE: To describe the experiences of patients with type 2 diabetes in a web
      based disease management programme based on an interactive electronic medical
      record. DESIGN: Qualitative analysis of semistructured interviews with patients
      enrolled in a diabetes care module that included access to their electronic
      medical record, secure email, ability to upload blood glucose readings, an
      education site with endorsed content, and an interactive online diary for
      entering exercise, diet, and medication. SETTING: Patients' homes in Washington
      state, United States. PARTICIPANTS: Nine participants aged 45-65 completed
      interviews before and after they used the programme. RESULTS: Six themes emerged:
      feeling that non-acute concerns are uniquely valued; enhanced sense of security
      about health and health care; frustration with unmet expectations; feeling more
      able to manage; valuing feedback; and difficulty fitting the programme into
      activities of daily life. Three themes--valuing non-acute concerns, feeling
      secure, and unmet expectations--have particular relevance to the design and use
      of web based tools for care of patients with diabetes and chronic medical
      conditions. CONCLUSION: Participants' experiences support further study of open
      access to the electronic medical record and online communication between patients
      and their care providers. The development of web based disease management
      programmes should take into account the specific needs and expectations of
      patients, and patients and providers should have candid discussions about what
      web based care can and cannot provide.

PMID- 15142920
TI  - Doctors' experience with handheld computers in clinical practice: qualitative
      study.
AB  - OBJECTIVE: To examine doctors' perspectives about their experiences with handheld
      computers in clinical practice. DESIGN: Qualitative study of eight focus groups
      consisting of doctors with diverse training and practice patterns. SETTING: Six
      practice settings across the United States and two additional focus group
      sessions held at a national meeting of general internists. PARTICIPANTS: 54
      doctors who did or did not use handheld computers. RESULTS: Doctors who used
      handheld computers in clinical practice seemed generally satisfied with them and
      reported diverse patterns of use. Users perceived that the devices helped them
      increase productivity and improve patient care. Barriers to use concerned the
      device itself and personal and perceptual constraints, with perceptual factors
      such as comfort with technology, preference for paper, and the impression that
      the devices are not easy to use somewhat difficult to overcome. Participants
      suggested that organisations can help promote handheld computers by providing
      advice on purchase, usage, training, and user support. Participants expressed
      concern about reliability and security of the device but were particularly
      concerned about dependency on the device and over-reliance as a substitute for
      clinical thinking. CONCLUSIONS: Doctors expect handheld computers to become more
      useful, and most seem interested in leveraging (getting the most value from)
      their use. Key opportunities with handheld computers included their use as a
      stepping stone to build doctors' comfort with other information technology and
      ehealth initiatives and providing point of care support that helps improve
      patient care.

PMID- 15142921
TI  - Health related virtual communities and electronic support groups: systematic
      review of the effects of online peer to peer interactions.
AB  - OBJECTIVE: To compile and evaluate the evidence on the effects on health and
      social outcomes of computer based peer to peer communities and electronic self
      support groups, used by people to discuss health related issues remotely. DESIGN
      AND DATA SOURCES: Analysis of studies identified from Medline, Embase, CINAHL,
      PsycINFO, Evidence Based Medicine Reviews, Electronics and Communications
      Abstracts, Computer and Information Systems Abstracts, ERIC, LISA, ProQuest
      Digital Dissertations, Web of Science. SELECTION OF STUDIES: We searched for
      before and after studies, interrupted time series, cohort studies, or studies
      with control groups; evaluating health or social outcomes of virtual peer to peer
      communities, either as stand alone interventions or in the context of more
      complex systems with peer to peer components. MAIN OUTCOME MEASURES: Peer to peer
      interventions and co-interventions studied, general characteristics of studies,
      outcome measures used, and study results. RESULTS: 45 publications describing 38
      distinct studies met our inclusion criteria: 20 randomised trials, three meta
      analyses of n of 1 trials, three non-randomised controlled trials, one cohort
      study, and 11 before and after studies. Only six of these evaluated "pure" peer
      to peer communities, and one had a factorial design with a "peer to peer only"
      arm, whereas 31 studies evaluated complex interventions, which often included
      psychoeducational programmes or one to one communication with healthcare
      professionals, making it impossible to attribute intervention effects to the peer
      to peer community component. The outcomes measured most often were depression and
      social support measures; most studies did not show an effect. We found no
      evidence to support concerns over virtual communities harming people.
      CONCLUSIONS: No robust evidence exists of consumer led peer to peer communities,
      partly because most peer to peer communities have been evaluated only in
      conjunction with more complex interventions or involvement with health
      professionals. Given the abundance of unmoderated peer to peer groups on the
      internet, research is required to evaluate under which conditions and for whom
      electronic support groups are effective and how effectiveness in delivering
      social support electronically can be maximised.

PMID- 15142922
TI  - Prescribing safety features of general practice computer systems: evaluation
      using simulated test cases.

PMID- 15142923
TI  - Computer aided prescribing leaves holes in the safety net.

PMID- 15142925
TI  - International online discussion lists on chronic myelogenous leukaemia.

PMID- 15142924
TI  - Soft networks for bridging the gap between research and practice: illuminative
      evaluation of CHAIN.
AB  - OBJECTIVES: To explore the process of knowledge exchange in an informal email
      network for evidence based health care, to illuminate the value of the service
      and its critical success factors, and to identify areas for improvement. DESIGN:
      Illuminative evaluation. SETTING: Targeted email and networking service for UK
      healthcare practitioners and researchers. PARTICIPANTS: 2800 members of a
      networking service. MAIN OUTCOME MEASURES: Tracking of email messages, interviews
      with core staff, and a qualitative analysis of messages, postings from focus
      groups, and invited and unsolicited feedback to the service. RESULTS: The
      informal email network helped to bridge the gap between research and practice by
      serving as a rich source of information, providing access to members'
      experiences, suggestions, and ideas, facilitating cross boundary collaboration,
      and enabling participation in networking at a variety of levels. Ad hoc groupings
      and communities of practice emerged spontaneously as members discovered common
      areas of interest. CONCLUSION: This study illuminated how knowledge for evidence
      based health care can be targeted, personalised, and made meaningful through
      informal social processes. Critical success factors include a broad based
      membership from both the research and service communities; a loose and fluid
      network structure; tight targeting of messages based on members' interests; the
      presence of a strong network identity and culture of reciprocity; and the
      opportunity for new members to learn through passive participation.

PMID- 15142926
TI  - Advertising campaign on a major internet search engine to promote colorectal
      cancer screening.

PMID- 15142927
TI  - Critical care medicine mailing list: growth of an online forum.

PMID- 15142928
TI  - Handheld computers.

PMID- 15142930
TI  - Learning from e-patients at Massachusetts General Hospital.

PMID- 15142929
TI  - The clinician's perspective on electronic health records and how they can affect
      patient care.

PMID- 15142931
TI  - HINARI: bridging the global information divide.

PMID- 15142933
TI  - Four rules for the reinvention of health care.

PMID- 15142932
TI  - Digital bridges need concrete foundations: lessons from the Health InterNetwork
      India.

PMID- 15142934
TI  - NHS national programme for information technology: programme erodes
      confidentiality of medical records.

PMID- 15142935
TI  - NHS national programme for information technology: changes must involve
      clinicians and show the value to patient care.

PMID- 15142936
TI  - Internet access is a socioeconomic issue.

PMID- 15142937
TI  - Sustainability of medical imaging: to obtain informed consent from everyone is
      impossible.

PMID- 15142938
TI  - Use of healthcare resources in the last six months of life: findings should be
      approached with caution outside United States.

PMID- 15142939
TI  - Use of healthcare resources in the last six months of life: paper contains
      absolutely gorgeous and diverting sentence.

PMID- 15142940
TI  - Use of healthcare resources in the last six months of life: how doctors learn may
      explain results.

PMID- 15142941
TI  - Alcohol evidence and policy: harm reduction strategy is triumph of spin over
      substance.

PMID- 15142942
TI  - Alcohol evidence and policy: alternative tax strategy is possible.

PMID- 15142943
TI  - Evidence base: rock of certainty or shifting sands? Not a rock of certainty--but
      stepping stones?

PMID- 15142944
TI  - Evidence base: rock of certainty or shifting sands? Where is the evidence for
      "evidence based"?

PMID- 15142945
TI  - Alcohol evidence and policy: beliefs and evidence: asking question might help.

PMID- 15142947
TI  - Alcohol evidence and policy: decimalise measure of alcohol.

PMID- 15142946
TI  - Universal consent form might help.

PMID- 15142948
TI  - Variability in end of life care.

PMID- 15142950
TI  - Expression of mutant p193 and p53 permits cardiomyocyte cell cycle reentry after
      myocardial infarction in transgenic mice.
AB  - Previous studies have demonstrated that expression of p193 and p53 mutants with
      dominant-interfering activities renders embryonic stem cell-derived
      cardiomyocytes responsive to the growth promoting activities of the E1A viral
      oncoproteins. In this study, the effects of p53 and p193 antagonization on
      cardiomyocyte cell cycle activity in normal and infarcted hearts were examined.
      Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants
      in the heart were generated. Transgene expression had no effect on cardiomyocyte
      cell cycle activity in uninjured adult hearts. In contrast expression of either
      transgene resulted in a marked induction of cardiomyocyte cell cycle activity at
      the infarct border zone at 4 weeks after permanent coronary artery occlusion.
      Expression of the p193 dominant-interfering mutant was also associated with an
      induction of cardiomyocyte DNA synthesis in the interventricular septa of
      infarcted hearts. A concomitant and marked reduction in hypertrophic
      cardiomyocyte growth was observed in the septa of hearts expressing the p193
      dominant-interfering transgene, suggesting that cell cycle activation might
      partially counteract the adverse ventricular remodeling that occurs after
      infarction. Collectively these data suggest that antagonization of p193 and p53
      activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle
      reentry in the injured adult heart.

PMID- 15142952
TI  - Visual binding through reentrant connectivity and dynamic synchronization in a
      brain-based device.
AB  - Effective visual object recognition requires mechanisms to bind object features
      (e.g. color, shape and motion) while distinguishing distinct objects.
      Synchronously active neuronal circuits among reentrantly connected cortical areas
      may provide a basis for visual binding. To assess the potential of this
      mechanism, we have constructed a mobile brain-based device, Darwin VIII, which is
      guided by simulated analogues of cortical and sub-cortical areas required for
      visual processing, decision-making, reward and motor responses. These simulated
      areas are reentrantly connected and each area contains neuronal units
      representing both the mean activity level and the relative timing of the activity
      of groups of neurons. Darwin VIII learns to discriminate among multiple objects
      with shared visual features and associates 'target' objects with innately
      preferred auditory cues. We observed the co-activation of globally distributed
      neuronal circuits that corresponded to distinct objects in Darwin VIII's visual
      field. These circuits, which are constrained by a reentrant neuroanatomy and
      modulated by behavior and synaptic plasticity, are necessary for successful
      discrimination. By situating Darwin VIII in a rich real-world environment
      involving continual changes in the size and location of visual stimuli due to
      self-generated movement, and by recording its behavioral and neuronal responses
      in detail, we were able to show that reentrant connectivity and dynamic
      synchronization provide an effective mechanism for binding the features of visual
      objects.

PMID- 15142951
TI  - Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple
      signaling pathways in agonist control of H(P)ETE synthesis.
AB  - Lipoxygenases (LOX) contribute to vascular disease and inflammation through
      generation of bioactive lipids, including 12-hydro(pero)xyeicosatetraenoic acid
      (12-H(P)ETE). The physiological mechanisms that acutely control LOX product
      generation in mammalian cells are uncharacterized. Human platelets that contain a
      12-LOX isoform (p12-LOX) were used to define pathways that activate H(P)ETE
      synthesis in the vasculature. Collagen and collagen-related peptide (CRP) (1 to
      10 microg/mL) acutely induced platelet 12-H(P)ETE synthesis. This implicated the
      collagen receptor glycoprotein VI (GPVI), which signals via the immunoreceptor
      based activatory motif (ITAM)-containing FcRgamma chain. Conversely, thrombin
      only activated at high concentrations (> 0.2 U/mL), whereas U46619 and ADP alone
      were ineffective. Collagen or CRP-stimulated 12-H(P)ETE generation was inhibited
      by staurosporine, PP2, wortmannin, BAPTA/AM, EGTA, and L-655238, implicating src
      tyrosine kinases, PI3-kinase, Ca2+ mobilization, and p12-LOX translocation. In
      contrast, protein kinase C (PKC) inhibition potentiated 12-H(P)ETE generation.
      Finally, activation of the immunoreceptor tyrosine-based inhibitory motif (ITIM)
      containing platelet endothelial cell adhesion molecule (PECAM-1) inhibited p12
      LOX product generation. This study characterizes a receptor-dependent pathway for
      12-H(P)ETE synthesis via the collagen receptor GPVI, which is negatively
      regulated by PECAM-1 and PKC, and demonstrates a novel link between immune
      receptor signaling and lipid mediator generation in the vasculature.

PMID- 15142953
TI  - Region specific micromodularity in the uppermost layers in primate cerebral
      cortex.
AB  - A micromodularity specific to the uppermost cortical layers, layers 1 and 2, is
      demonstrated in primates. This is most pronounced as patches of zinc-positive
      (Zn+) terminations, preferentially in the pre-Rolandic and limbic areas. The
      upper layer modularity can frequently be demonstrated by parvalbumin
      immunoreactive (PV-ir) GABAergic terminations and by bundles of apical dendrites.
      Double-labeling or alternate section analysis shows that PV-ir and Zn+
      terminations co-mingle at the layer 1,2 border and appear to coincide with
      dendritic bundles, proposed to originate from layer 2 pyramidal neurons. This
      model is basically similar to the prominent wall-and-hollow honeycomb
      organization in rat visual cortex. The organization of the PV-ir and dendritic
      components, however, is more difficult to define in primate than in rat.
      Moreover, the micromodularity is not uniform across areas. In some areas (motor
      and limbic), the modularity can be visualized by both zinc and PV. In other areas
      (i.e. primary sensory, sensory associational and prefrontal areas 46 and 8),
      although PV immunohistochemisty shows a periodic distribution, there is no
      detectable Zn+ modularity. These results add to the evidence for the complexity
      of layers 1 and 2 and raise the possibility that patches of Zn+ terminations
      correspond to zones of area-specific zinc-related plasticity. This might figure
      in the context of top-down or feedback influences, as often associated with layer
      1.

PMID- 15142954
TI  - The anatomy of spatial neglect based on voxelwise statistical analysis: a study
      of 140 patients.
AB  - A major challenge for any anatomical study of spatial neglect in neurological
      patients is that human lesions vary tremendously in extent and location between
      individuals. Approaches to this problem used in previous studies were to focus on
      subgroups of patients that are more homogeneous either with respect to the branch
      territory affected by the stroke or with respect to existing additional
      neurological symptoms (e.g. additional visual field defects). It could be argued
      that such strategies might bias the conclusions on the critical substrate
      associated with spatial neglect. The present study thus addressed the high
      variability inherent in naturally occurring lesions by using an unselected, but
      very large sample size and by comparing a neglect group with a non-neglect group
      using voxelwise statistical testing. We investigated an unselected 7 year sample
      of 140 consecutively admitted patients with right hemisphere strokes. Seventy
      eight had spatial neglect, 62 did not show the disorder. The incidence of visual
      field defects was comparable in both groups. For assessing lesion location, in a
      first step, we used conventional lesion density plots together with subtraction
      analysis. Moreover, due to the large size of the sample voxelwise statistical
      testing was possible to objectively estimate which brain regions are more
      frequently compromised in neglect patients relative to patients without neglect.
      The results demonstrate that the right superior temporal cortex, the insula and
      subcortically putamen and caudate nucleus are the neural structures damaged
      significantly more often in patients with spatial neglect.

PMID- 15142955
TI  - Parieto-premotor areas mediate directional interference during bimanual
      movements.
AB  - In bimanual movements, interference emerges when limbs are moved simultaneously
      along incompatible directions. The neural substrate and mechanisms underlying
      this phenomenon are largely unknown. We used functional magnetic resonance
      imaging to compare brain activation during directional incompatible versus
      compatible bimanual movements. Our main results were that directional
      interference emerges primarily within superior parietal, intraparietal and dorsal
      premotor areas of the right hemisphere. The same areas were also activated when
      the unimanual subtasks were executed in isolation. In light of previous findings
      in monkeys and humans, we conclude that directional interference activates a
      parieto-premotor circuit that is involved in the control of goal-directed
      movements under somatosensory guidance. Moreover, our data suggest that the
      parietal cortex might represent an important locus for integrating spatial
      aspects of the limbs' movements into a common action. It is hypothesized to be
      the candidate structure from where interference arises when directionally
      incompatible movements are performed. We discuss the possibility that
      interference emerges when computational resources in these parietal areas are
      insufficient to code two incompatible movement directions independently from each
      other.

PMID- 15142956
TI  - Identification of the genes that are expressed in the upper layers of the
      neocortex.
AB  - Laminar specificity is one of the most striking features of neocortical
      circuitry. To explore the molecular basis of this specificity, particularly in
      relation to thalamocortical connectivity, we searched for the genes expressed in
      the upper cortical layers by constructing a subtraction cDNA library that was
      enriched for genes expressed in layer 4 of perinatal rat somatosensory cortex.
      Differential screening, sequence analysis and in situ hybridization demonstrated
      that a new unc5 family member (unc5h4), deltex-like gene, stem cell factor (SCF)
      and myocyte-specific enhancer factor-2C (MEF-2C) were specifically expressed in
      layer 4 or layers 2/3-4 at postnatal day 7, by when laminar organization and
      fundamental cortical circuitries have been established. In terms of regional
      specificity, unc5h4 and SCF signals were stronger in sensory cortices, whereas
      MEF-2C and deltex-like gene were expressed rather uniformly in all neocortical
      regions. Analysis during development demonstrated that expression of these genes
      was pronounced between late embryonic and early postnatal developmental stages,
      except for MEF-2C expression, which continued in later stages. These results
      demonstrate that certain types of molecules including transcription factors,
      receptor and ligand molecules, are expressed specifically in the upper layers of
      the developing neocortex, suggesting a role in laminar specification of cortical
      cells and circuitry.

PMID- 15142957
TI  - Gene expression analysis of the late embryonic mouse cerebral cortex using DNA
      microarray: identification of several region- and layer-specific genes.
AB  - The mammalian neocortex develops layer organizations with regional differences
      represented by expression of multiple genes at embryonic stages. These genes
      could play important roles in the formation of areal cyto-architecture, yet, the
      number of genes identified so far is not sufficient to explain such intricate
      processes. Here we collected five regions--the medial, dorsal, lateral, rostral
      and occipital--from the dissected E16.5 mouse cerebral cortex and performed
      extensive gene expression analysis using the Affymetrix U74Av2 array with probes
      for 12,500 genes. After relative quantitative analysis, 34, 33 and 15 genes were
      selected as highly expressed genes in the medial, dorsal and lateral regions,
      respectively. The combination of GeneChip system, real-time quantitative reverse
      transcription polymerase chain reaction and in situ hybridization analyses
      allowed the successful identification of seven genes from the dorsal region
      (Neuropeptide Y, Wnt7b, TGF-beta RI, Nrf3, Bcl-6, MT4-MMP and Rptp kappa), three
      genes from the medial region (Hop-pending, HtrA and Crystallin), and three genes
      from the lateral region (Somatostatin, Ngef and Fxyd7). Particularly, all seven
      genes identified in the dorsal region demarcated the future somatosensory and
      auditory areas in the cortical plate with high rostrolateral-low caudomedial
      gradation. Their expression patterns were not uniform, but delineated either the
      superficial or the deep layer in the cortical plate. Furthermore, the regional
      expression pattern of Neuropeptide Y was shifted rostrally and the layer
      specificity was disorganized in the Pax6-deficient mice. Our results provide new
      information about a subclass of regionally expressed genes in the cortical plate
      at the late embryonic stage, which may help understand the molecular mechanisms
      of neocortical arealization.

PMID- 15142958
TI  - Spike-timing dynamics of neuronal groups.
AB  - A neuronal network inspired by the anatomy of the cerebral cortex was simulated
      to study the self-organization of spiking neurons into neuronal groups. The
      network consisted of 100 000 reentrantly interconnected neurons exhibiting known
      types of cortical firing patterns, receptor kinetics, short-term plasticity and
      long-term spike-timing-dependent plasticity (STDP), as well as a distribution of
      axonal conduction delays. The dynamics of the network allowed us to study the
      fine temporal structure of emerging firing patterns with millisecond resolution.
      We found that the interplay between STDP and conduction delays gave rise to the
      spontaneous formation of neuronal groups--sets of strongly connected neurons
      capable of firing time-locked, although not necessarily synchronous, spikes.
      Despite the noise present in the model, such groups repeatedly generated patterns
      of activity with millisecond spike-timing precision. Exploration of the model
      allowed us to characterize various group properties, including spatial
      distribution, size, growth, rate of birth, lifespan, and persistence in the
      presence of synaptic turnover. Localized coherent input resulted in shifts of
      receptive and projective fields in the model similar to those observed in vivo.

PMID- 15142959
TI  - Mental visual synthesis is originated in the fronto-temporal network of the left
      hemisphere.
AB  - Mental visual synthesis is the capacity for experiencing, constructing, or
      manipulating 'mental imagery'. To investigate brain networks involved in mental
      visual synthesis, brain activity was measured in right-handed healthy volunteers
      during mental imagery tasks, in which the subjects were instructed to imagine a
      novel object, that does not exist in the real world, by composing it from two
      visually presented words associated with a real object or two achromatic line
      drawings of a real object, using functional magnetic resonance imaging (fMRI).
      Both tasks activated the same areas in the inferior frontal and inferior temporal
      cortices of the left hemisphere. Our results indicate that the source of mental
      visual synthesis may be formed by activity of a brain network consisting of these
      areas, which are also involved in semantic operations and visual imagery.

PMID- 15142960
TI  - Chemically specific circuit composed of vesicular glutamate transporter 3- and
      preprotachykinin B-producing interneurons in the rat neocortex.
AB  - The third vesicular glutamate transporter, VGLUT3, is distributed in cell bodies
      of neocortical neurons and axon terminals mainly in the superficial part of layer
      II/III of the cerebral cortex. We examined the chemical characteristics of VGLUT3
      expressing neurons by immunohistochemistry in the rat neocortex. Since the vast
      majority of VGLUT3-immunoreactive neurons showed immunoreactivities for GABA,
      preprotachykinin B (PPTB) and cholecystokinin, VGLUT3-immunoreactive neocortical
      neurons were considered to constitute a subgroup of GABAergic interneurons.
      VGLUT3-immunoreactive axon terminals were immunopositive for either vesicular
      GABA transporter (VGAT) or serotonin. These results together with anterograde
      tracer injection and chemical lesion experiments in the dorsal and median raphe
      nuclei revealed that the neocortex contains at least two kinds of VGLUT3-laden
      axon terminals: one is serotonergic and derived from the raphe nuclei, and the
      other is GABAergic and intrinsic in the neocortex. Furthermore, many VGLUT3/VGAT
      immunoreactive terminals formed axon baskets and made axosomatic symmetric
      synapses on neocortical neurons, most of which were immunoreactive for PPTB.
      VGLUT3-immunopositive axon baskets surrounded about a half of PPTB-positive and
      almost all VGLUT3-positive neurons. Thus, VGLUT3-expressing GABAergic
      interneurons form a chemically specific circuit within the PPTB-producing
      interneuron group and it is likely that glutamate is used within the chemically
      specific circuit.

PMID- 15142961
TI  - Catecholaminergic consolidation of motor cortical neuroplasticity in humans.
AB  - Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve
      neuroplastic mechanisms in humans. However, so far not much is known about the
      underlying physiological mechanisms. Here, we study the impact of amphetamine on
      NMDA receptor-dependent long-lasting excitability modifications in the human
      motor cortex elicited by weak transcranial direct current stimulation (tDCS).
      Amphetamine significantly enhanced and prolonged increases in anodal, tDCS
      induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS
      resulted in an enhancement of excitability which lasted until the morning after
      tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the
      excitability enhancement was most pronounced for long-term effects; the duration
      of short-term excitability enhancement was only slightly increased. Since the
      additional application of the NMDA receptor antagonist dextromethorphane blocked
      any enhancement of tDCS-driven excitability under amphetamine, we conclude that
      amphetamine consolidates the tDCS-induced neuroplastic effects, but does not
      initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished
      the duration of the tDCS-generated after-effects suggests that adrenergic
      receptors play a certain role in the consolidation of NMDA receptor-dependent
      motor cortical excitability modifications in humans. This result may enable
      researchers to optimize neuroplastic processes in the human brain on the rational
      basis of purpose-designed pharmacological interventions.

PMID- 15142962
TI  - Correlated functional changes of the prefrontal cortex in twins induced by
      classroom education of second language.
AB  - As the neural substrates of second language (L2) acquisition are largely unknown,
      they may or may not be similar to those of first language (L1) representation. We
      used functional imaging to examine whether training in the conjugation of English
      verbs from present to past tense alters brain activations in 13-year-old twins. A
      novel experimental design contrasted past tense verb identification and verb
      matching, which were tested in either English (L2) or Japanese (L1). After 2
      month classroom training in the past tense using bingo games, the two individuals
      in each pair exhibited significantly correlated performances. When pre- and post
      scanning sessions were compared with each other for L2, the left dorsal inferior
      frontal gyrus (IFG) exhibited significantly correlated activation increases
      within each pair of twins and the increases were positively correlated with
      individual performance improvements. Moreover, the cortical plasticity for L2
      acquisition was guided toward the L1 specialization of the left dorsal IFG, in
      spite of notable differences between L1 and L2 in the students' linguistic
      knowledge and in their performance in making past tense forms. These findings
      suggest a cortical mechanism underlying L2 acquisition, which critically depends
      on shared genetic and environmental factors for each twin in a surprisingly
      predictive manner.

PMID- 15142963
TI  - Sex-related differences in a gambling task and its neurological correlates.
AB  - We investigated sex-related differences in task performance and brain activity in
      the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) during
      performance of a decision-making task (the Iowa Gambling Task). When men and
      women were examined separately, men activated extensive regions of the right
      lateral OFC and right DLPFC, as well as the left lateral OFC. In contrast, women
      activated the left medial OFC. Examining sex differences directly, men showed
      better task performance and greater lateralized brain activity to the right
      hemisphere than women. This was exemplified by greater activation in a large area
      of the right lateral OFC of men during their performance of the Iowa Gambling
      Task. In contrast, women had greater activation in the left DLPFC, left medial
      frontal gyrus and temporal lobe during this task. Thus, brain mechanisms engaged
      by men and women when solving the same decision-making task are different. These
      observations indicate that sex-related differences contribute to the
      heterogeneity observed in both normal and abnormal brain functioning. These
      results also provide further evidence of sexual dimorphism in neurocognitive
      performance and brain function.

PMID- 15142964
TI  - Are there gender-specific neural substrates of route learning from different
      perspectives?
AB  - Psychological studies have demonstrated sex differences in performance and
      tactics for route learning. Route information can be encoded in different ways,
      such as the survey perspective (as in maps) and the route perspective (as we
      experience the world). Here we show, using functional magnetic resonance imaging,
      that men and women use the same brain areas to learn routes from both
      perspectives, and that the observed sex differences in route learning are not due
      to differences in the parts of the brain being used. We also show that many of
      the same brain areas are used in route learning from both perspectives, such as
      the parahippocampus, precuneus, posterior cingulate gyrus and middle frontal
      gyrus. However, paired comparisons of route learning from both perspectives shows
      that the survey perspective activates the superior and middle temporal gyri and
      the angular gyrus, which are not activated in the route perspective.

PMID- 15142965
TI  - The influence of hand posture on corticospinal excitability during motor imagery:
      a transcranial magnetic stimulation study.
AB  - In order to study the interaction between proprioceptive information and motor
      imagery, we herein investigate how compatible and incompatible postural signals
      influence corticospinal excitability during the mental simulation of hand
      movements. Subjects were asked to imagine themselves joining the tips of the
      thumb and the little finger while they maintained one of the two following hand
      postures: posture A (PA, compatible), little finger, index and thumb extended,
      the remaining fingers flexed; or posture B (PB, incompatible), index and thumb
      extended, other fingers flexed. All subjects rated the imagined finger opposition
      movements as easier to perform when the hand was kept in PA than in PB (P < 0.01)
      and the correlation between the duration of motor imagery and movement execution
      was also higher for PA than PB (P < 0.01). For each posture, motor evoked
      potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of
      the left motor cortex were recorded from the right opponens pollicis muscle
      during both motor imagery (MI) and rest (R) conditions. MEP area varied according
      to the hand posture: PA induced a higher increase in corticospinal excitability,
      when compared with PB. These results indicate that the actual limb posture
      affects the process of motor imagery. The source of this postural modulation
      effect is discussed.

PMID- 15142967
TI  - The serotonin transporter: a vehicle to elucidate pulmonary hypertension?

PMID- 15142968
TI  - Nitric oxide protects against pathological ventricular remodeling:
      reconsideration of the role of NO in the failing heart.

PMID- 15142969
TI  - Proteoglycans in atherosclerosis and restenosis: key roles for versican.
AB  - The proteoglycan versican is one of several extracellular matrix (ECM) molecules
      that accumulate in lesions of atherosclerosis and restenosis. Its unique
      structural features create a highly interactive molecule that binds growth
      factors, enzymes, lipoproteins, and a variety of other ECM components to
      influence fundamental events involved in vascular disease. Versican is one of the
      principal genes that is upregulated after vascular injury and is a prominent
      component in stented and nonstented restenotic lesions. The synthesis of versican
      is highly regulated by specific growth factors and cytokines and the principal
      source of versican is the smooth muscle cell. Versican interacts with hyaluronan,
      a long chain glycosaminoglycan, to create expanded viscoelastic pericellular
      matrices that are required for arterial smooth muscle cell (ASMC) proliferation
      and migration. Versican is also prominent in advanced lesions of atherosclerosis,
      at the borders of lipid-filled necrotic cores as well as at the plaque-thrombus
      interface, suggesting roles in lipid accumulation, inflammation, and thrombosis.
      Versican influences the assembly of ECM and controls elastic fiber
      fibrillogenesis, which is of fundamental importance in ECM remodeling during
      vascular disease. Collectively, these studies highlight the critical importance
      of this specific ECM component in atherosclerosis and restenosis.

PMID- 15142970
TI  - Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene
      expression in vascular cells.
AB  - A large body of data gathered over the past couple of years has identified the
      peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta
      as transcription factors exerting modulatory actions in vascular cells. PPARs,
      which belong to the nuclear receptor family of ligand-activated transcription
      factors, were originally described as gene regulators of various metabolic
      pathways. Although the PPARalpha, gamma, and beta/delta subtypes are
      approximately 60% to 80% homologous in their ligand- and DNA-binding domains,
      significant differences in ligand and target gene specificities are observed.
      PPARalpha is activated by polyunsaturated fatty acids and oxidized derivatives
      and by lipid-modifying drugs of the fibrate family, including fenofibrate or
      gemfibrozil. PPARalpha controls expression of genes implicated in lipid
      metabolism. PPARgamma, in contrast, is a key regulator of glucose homeostasis and
      adipogenesis. Ligands of PPARgamma include naturally occurring FA derivatives,
      such as hydroxyoctadecadienoic acids (HODEs), prostaglandin derivatives such as
      15-deoxyDelta12,14-prostaglandin J2, and glitazones, insulin-sensitizing drugs
      presently used to treat patients with type 2 diabetes. Ligands for PPARbeta/delta
      are polyunsaturated fatty acids, prostaglandins, and synthetic compounds, some of
      which are presently in clinical development. PPARbeta/delta stimulates fatty acid
      oxidation predominantly acting in muscle. All PPARs are expressed in vascular
      cells, where they exhibit antiinflammatory and antiatherogenic properties. In
      addition, studies in various animal models as well as clinical data suggest that
      PPARalpha and PPARgamma activators can modulate atherogenesis in vivo. At
      present, no data are available relating to possible effects of PPARbeta/delta
      agonists on atherogenesis. Given the widespread use of PPARalpha and PPARgamma
      agonists in patients at high risk for cardiovascular disease, the understanding
      of their function in the vasculature is not only of basic interest but also has
      important clinical implications. This review will focus on the role of PPARs in
      the vasculature and summarize the present understanding of their effects on
      atherogenesis and its cardiovascular complications.

PMID- 15142971
TI  - The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice.
AB  - Recent work has identified LDL receptor-related family members, Lrp5 and Lrp6, as
      co-receptors for the transduction of Wnt signals. Our analysis of mice carrying
      mutations in both Lrp5 and Lrp6 demonstrates that the functions of these genes
      are redundant and are essential for gastrulation. Lrp5;Lrp6 double homozygous
      mutants fail to establish a primitive streak, although the anterior visceral
      endoderm and anterior epiblast fates are specified. Thus, Lrp5 and Lrp6 are
      required for posterior patterning of the epiblast, consistent with a role in
      transducing Wnt signals in the early embryo. Interestingly, Lrp5(+/-);Lrp6(-/-)
      embryos die shortly after gastrulation and exhibit an accumulation of cells at
      the primitive streak and a selective loss of paraxial mesoderm. A similar
      phenotype is observed in Fgf8 and Fgfr1 mutant embryos and provides genetic
      evidence in support of a molecular link between the Fgf and Wnt signaling
      pathways in patterning nascent mesoderm. Lrp5(+/-);Lrp6(-/-) embryos also display
      an expansion of anterior primitive streak derivatives and anterior neurectoderm
      that correlates with increased Nodal expression in these embryos. The effect of
      reducing, but not eliminating, Wnt signaling in Lrp5(+/-);Lrp6(-/-) mutant
      embryos provides important insight into the interplay between Wnt, Fgf and Nodal
      signals in patterning the early mouse embryo.

PMID- 15142972
TI  - A broad competence to respond to SHORT ROOT revealed by tissue-specific ectopic
      expression.
AB  - In plants, cell fate specification depends primarily on position rather than
      lineage. Recent results indicate that positional information can be transmitted
      through intercellular trafficking of transcription factors. The SHORT ROOT (SHR)
      gene, a member of the GRAS family of putative transcription factors, is involved
      in root radial patterning in Arabidopsis. Correct radial patterning depends on
      the positional information transmitted through limited SHR intercellular movement
      and translated into cell division and specification by competent target cells. To
      investigate the regulation of SHR movement and the competence to respond to it,
      we drove expression of a translational fusion SHR::GFP using four different
      tissue-specific promoters. In a wild-type background, SHR::GFP was not able to
      move from either phloem companion cells or epidermal cells, both of which have
      been shown to support movement of other proteins, suggesting a requirement for
      tissue-specific factors for SHR movement. When expressed from its native promoter
      in plants with multiple endodermal layers, SHR::GFP was not able to move beyond
      the first endodermal layer, indicating that movement is not limited by a
      mechanism that recognizes boundaries between cell types. Surprisingly, movement
      of SHR::GFP was observed when ectopic expression from an epidermal promoter was
      placed in a scarecrow (scr) mutant background, revealing a possible role for SCR
      in limiting movement. Analysis of the competence to respond to SHR-mediated cell
      specification activity indicated that it was broadly distributed in the epidermal
      lineage, while competence to respond to the cell division activity of SHR
      appeared limited to the initials and involved induction of SCR. The spatial
      distribution of competence to respond to SHR highlights the importance of tightly
      regulated movement in generating the root radial pattern.

PMID- 15142973
TI  - A role for MKP3 in axial patterning of the zebrafish embryo.
AB  - Fibroblast growth factors (FGFs) are secreted molecules that can activate the
      RAS/mitogen-activated protein kinase (MAPK) pathway to serve crucial functions
      during embryogenesis. Through an in situ hybridization screen for genes with
      restricted expression patterns during early zebrafish development, we identified
      a group of genes that exhibit similar expression patterns to FGF genes. We report
      the characterization of zebrafish MAP kinase phosphatase 3 (MKP3; DUSP6 -
      Zebrafish Information Network), a member of the FGF synexpression group, showing
      that it has a crucial role in the specification of axial polarity in the early
      zebrafish embryo. MKP3 dephosphorylates the activated form of MAPK, inhibiting
      the RAS/MAPK arm of the FGF signaling pathway. Gain- and loss-of-function studies
      reveal that MKP3 is required to limit the extent of FGF/RAS/MAPK signaling in the
      early embryo, and that disturbing this inhibitory pathway disrupts dorsoventral
      patterning at the onset of gastrulation. The earliest mkp3 expression is
      restricted to the future dorsal region of the embryo where it is initiated by a
      maternal beta-catenin signal, but soon after its initiation, mkp3 expression
      comes under the control of FGF signaling. Thus, mkp3 encodes a feedback
      attenuator of the FGF pathway, the expression of which is initiated at an early
      stage so as to ensure correct FGF signaling levels at the time of axial
      patterning.

PMID- 15142974
TI  - An interactive network of zinc-finger proteins contributes to regionalization of
      the Drosophila embryo and establishes the domains of HOM-C protein function.
AB  - During animal development, the HOM-C/HOX proteins direct axial patterning by
      regulating region-specific expression of downstream target genes. Though much is
      known about these pathways, significant questions remain regarding the mechanisms
      of specific target gene recognition and regulation, and the role of co-factors.
      From our studies of the gnathal and trunk-specification proteins Disconnected
      (DISCO) and Teashirt (TSH), respectively, we present evidence for a network of
      zinc-finger transcription factors that regionalize the Drosophila embryo. Not
      only do these proteins establish specific regions within the embryo, but their
      distribution also establishes where specific HOM-C proteins can function. In this
      manner, these factors function in parallel to the HOM-C proteins during axial
      specification. We also show that in tsh mutants, disco is expressed in the trunk
      segments, probably explaining the partial trunk to head transformation reported
      in these mutants, but more importantly demonstrating interactions between members
      of this regionalization network. We conclude that a combination of regionalizing
      factors, in concert with the HOM-C proteins, promotes the specification of
      individual segment identity.

PMID- 15142975
TI  - The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural
      precursor cells.
AB  - Neural precursor cells (NPCs) have the ability to self-renew and to give rise to
      neuronal and glial lineages. The fate decision of NPCs between proliferation and
      differentiation determines the number of differentiated cells and the size of
      each region of the brain. However, the signals that regulate the timing of
      neuronal differentiation remain unclear. Here, we show that Wnt signaling
      inhibits the self-renewal capacity of mouse cortical NPCs, and instructively
      promotes their neuronal differentiation. Overexpression of Wnt7a or of a
      stabilized form of beta-catenin in mouse cortical NPC cultures induced neuronal
      differentiation even in the presence of Fgf2, a self-renewal-promoting factor in
      this system. Moreover, blockade of Wnt signaling led to inhibition of neuronal
      differentiation of cortical NPCs in vitro and in the developing mouse neocortex.
      Furthermore, the beta-catenin/TCF complex appears to directly regulate the
      promoter of neurogenin 1, a gene implicated in cortical neuronal differentiation.
      Importantly, stabilized beta-catenin did not induce neuronal differentiation of
      cortical NPCs at earlier developmental stages, consistent with previous reports
      indicating self-renewal-promoting functions of Wnts in early NPCs. These findings
      may reveal broader and stage-specific physiological roles of Wnt signaling during
      neural development.

PMID- 15142976
TI  - Natriuretic peptides as markers of mild forms of left ventricular dysfunction:
      effects of assays on diagnostic performance of markers.
AB  - BACKGROUND: We compared the performance of different natriuretic peptides to
      diagnose mild forms of left ventricular dysfunction (LVD) and investigated the
      influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT
      proBNP) with different assays on the diagnostic performance of these markers.
      METHODS: We measured BNP (Triage BNP), NT-proBNP (Biomedica), and N-terminal pro
      A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients
      (age range, 28-83 years) with clinically suspected mild LVD. In patients with
      sufficient sample volume, we measured BNP and NT-proBNP with additional assays
      (Shionoria and Roche, respectively). RESULTS: For identifying patients with mild
      systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence
      interval) areas under the curves (AUC) of 0.78 (0.63-0.89) and 0.75 (0.58-0.87),
      respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48
      0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays
      (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed
      equally well for the diagnosis of systolic LVD despite the poor agreement between
      NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic
      performance of the Triage BNP [AUC, 0.70 (0.56-0.81)] was significantly better (P
      = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34-0.65)]. Furthermore, the
      performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03)
      than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD.
      CONCLUSIONS: The performance of BNP for the diagnosis of systolic or diastolic
      LVD is not affected by the assay used, whereas the performance of NT-proBNP for
      the diagnosis of isolated diastolic LVD is assay dependent.

PMID- 15142977
TI  - D-dimer testing for deep venous thrombosis: a metaanalysis.
AB  - BACKGROUND: The use of D-dimer assays as a rule-out test for deep venous
      thrombosis (DVT) is controversial. To clarify this issue we performed a
      systematic review of the relevant literature. METHODS: We identified eligible
      studies, using MEDLINE entries from February 1995 through October 2003,
      supplemented by a review of bibliographies of relevant articles. Studies
      reporting accuracy evaluations comparing D-dimer test results with lower
      extremity ultrasound or venography in symptomatic patients with suspected acute
      DVT were selected for review. Two reviewers critically appraised each study
      independently according to previously established methodologic standards for
      diagnostic test research. Those studies judged to be of highest quality were
      designated Level 1. RESULTS: The 23 Level 1 studies reported data on 21 different
      D-dimer assays. There was wide variation in assay sensitivity, specificity, and
      negative predictive values, and major differences in methodology of reviewed
      studies. A multivariate analysis of assay performance, controlling for sample
      size, DVT prevalence, reference standard, and patient mix, found few differences
      among the assays in effect on test performance as measured by diagnostic odds
      ratio. Increasing prevalence of DVT was associated with poorer test performance
      (P = 0.01), whereas the choice of venography as the reference standard was
      associated with better test performance (P <0.005). CONCLUSIONS: Explanations for
      the wide variation in assay performance include differences in biochemical and
      technical characteristics of the assays, heterogeneity and small size of patient
      groups, and bias introduced by choice of reference standards. Assay sensitivity
      and negative predictive value were frequently <90%, uncharacteristic of a good
      rule-out test. General use of D-dimer assays as a stand-alone test for the
      diagnosis of DVT is not supported by the literature.

PMID- 15142978
TI  - ROC curves in clinical chemistry: uses, misuses, and possible solutions.
AB  - BACKGROUND: ROC curves have become the standard for describing and comparing the
      accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by
      clinical chemists. Our aims were to observe how the accuracy of clinical
      laboratory diagnostic tests is assessed, compared, and reported in the
      literature; to identify common problems with the use of ROC curves; and to offer
      some possible solutions. METHODS: We reviewed every original work using ROC
      curves and published in Clinical Chemistry in 2001 or 2002. For each article we
      recorded phase of the research, prospective or retrospective design, sample size,
      presence/absence of confidence intervals (CIs), nature of the statistical
      analysis, and major analysis problems. RESULTS: Of 58 articles, 31% were phase I
      (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced)
      studies. The studies increased in sample size from phase I to III and showed a
      progression in the use of prospective designs. Most phase I studies were powered
      to assess diagnostic tests with ROC areas >/=0.70. Thirty-eight percent of
      studies failed to include CIs for diagnostic test accuracy or the CIs were
      constructed inappropriately. Thirty-three percent of studies provided
      insufficient analysis for comparing diagnostic tests. Other problems included
      dichotomization of the gold standard scale and inappropriate analysis of the
      equivalence of two diagnostic tests. CONCLUSION: We identify available software
      and make some suggestions for sample size determination, testing for equivalence
      in diagnostic accuracy, and alternatives to a dichotomous classification of a
      continuous-scale gold standard. More methodologic research is needed in areas
      specific to clinical chemistry.

PMID- 15142979
TI  - Comparison of ultracentrifugation and nuclear magnetic resonance spectroscopy in
      the quantification of triglyceride-rich lipoproteins after an oral fat load.
AB  - BACKGROUND: The measurement of triglyceride (TG)-rich particles after an oral fat
      challenge has been used to provide a measure of risk for coronary artery disease
      independent of the fasting plasma triglyceride concentration. The analytical
      "gold standard" for measuring TG-rich lipoproteins uses density gradient
      ultracentrifugation; however, this technique is labor-intensive. Because of our
      need to perform numerous postprandial analyses of TG-rich lipoproteins for a
      large interventional study (Genetics of Lipid Lowering Drugs and Diet Network),
      we evaluated the use of nuclear magnetic resonance (NMR) spectroscopy for
      measuring TG-rich particles. METHODS: EDTA-blood samples were obtained 0, 3.5, 6,
      and 8 h after ingestion of an oral fat meal (89% of calories from fat) in 20
      apparently healthy individuals. The plasma TG concentrations of chylomicron and
      chylomicron remnant/VLDL fractions were analyzed by ultracentrifugation and NMR
      spectroscopy. RESULTS: Comparison of all values (n = 78) by ultracentrifugation
      (x) and NMR (y) produced a linear regression equation of y = 0.979x - 0.035
      mmol/L (R(2) = 0.90) for chylomicrons and y = 1.398x + 0.067 mmol/L (R(2) = 0.96)
      for the fraction containing chylomicron remnants and VLDL. Postprandial response
      of chylomicrons and chylomicron remnant/VLDL was similar, with maximum response
      occurring between 3.5 to 6 h regardless of method of measurement. CONCLUSION:
      Chylomicron and chylomicron remnant/VLDL fraction measurements obtained by NMR
      have a high degree of correlation with results produced by ultracentrifugation.
      NMR may therefore be suitable as an alternative method for the measurement of
      postprandial TG-rich lipoproteins in individuals consuming a high-fat meal.

PMID- 15142980
TI  - Genomic structure and characterization of the 5'-flanking region of the human
      ghrelin gene.
AB  - Ghrelin, an endogenous ligand for the GH secretagogue receptor, induces GH
      secretion, food intake, and positive energy balance. Although ghrelin exhibits a
      variety of hormonal actions, the mechanisms regulating ghrelin expression and
      secretion remain unclear. To understand regulation of human ghrelin gene
      expression, we examined the genomic structure of approximately 5,000 bp of the 5'
      flanking region of the human ghrelin gene. We performed rapid amplification of
      cDNA ends to estimate transcriptional start sites, indicating that there are two
      transcriptional initiation sites within the human ghrelin gene. Both transcripts
      were equally expressed in the human stomach, whereas the longer transcript was
      mainly expressed in a human medullary thyroid carcinoma (TT) cell line.
      Functional analysis using promoter-reporter constructs containing the 5'-flanking
      region of the gene indicated that the sequence residing within the -349 to -193
      region is necessary for human ghrelin promoter function in TT cells. Within this
      region existed several consensus sequences for a number of transactivating
      regulatory proteins, including an E-box site. Destruction of this site decreased
      to 40% of the promoter activity. The upstream region of the promoter has two
      additional putative E-box sites, and site-directed mutagenesis suggested that
      these are also involved in promoter activation. Electrophoretic mobility shift
      assays demonstrated that the upstream stimulatory factor specifically bound to
      these E-box elements. These results suggest a potential role for upstream
      stimulatory factor transcription factors in the regulation of human ghrelin
      expression.

PMID- 15142981
TI  - Ghrelin gene expression is markedly higher in fetal pancreas compared with fetal
      stomach: effect of maternal fasting.
AB  - Ghrelin is an orexigenic peptide secreted mainly by the stomach in adult rats.
      Ghrelin concentrations increase with fasting and decrease after food intake.
      Ghrelin is also present in the placenta and in the fetal stomach, but the role of
      fetal ghrelin remains unclear. In this study, we compared changes in plasma
      ghrelin, insulin, and glucose concentrations and in ghrelin gene expression in
      stomach, pancreas, and placenta in response to fasting and feeding in adult
      nonpregnant rats and in 20-d pregnant dams and their fetuses. Plasma total
      ghrelin concentrations were three times higher in the fetus than in the dam but
      did not increase in response to fasting. In contrast to total ghrelin, plasma
      active ghrelin concentrations wee 50% lower in the fetus compared with the adult
      pregnant rat. Ghrelin mRNA and total ghrelin were markedly elevated in the fetal
      pancreas and six to seven times greater than in the fetal stomach but were not
      affected by fasting. In contrast, fetal pancreas and stomach active ghrelin
      concentrations increased two to three times after maternal fasting. Ghrelin
      receptor mRNA was present in all fetal pancreas samples. Placenta ghrelin gene
      expression was detectable but low. These data raise the possibility that in the
      fetus, in contrast to the adult, the pancreas and not the stomach is a major
      source of circulating immunoreactive ghrelin. Furthermore, the presence of a
      strong ghrelin gene expression and of ghrelin receptor mRNA in the fetal pancreas
      is intriguing and suggests that ghrelin may play an important role in beta-cell
      development.

PMID- 15142982
TI  - Stressor-selective role of the ventral subiculum in regulation of neuroendocrine
      stress responses.
AB  - The ventral subiculum (vSUB) confers inhibitory effects of the hippocampus on
      hypothalamo-pituitary-adrenocortical (HPA) axis responses to novelty and
      restraint. The current study was designed to evaluate the role of the vSUB in
      regulating HPA axis responses to stressors of diverse modalities. Male Sprague
      Dawley rats received bilateral ibotenic acid or saline injections into the region
      of the vSUB. Corticosterone secretion was assessed after exposure to hypoxia and
      elevated plus maze, with the two stress exposures occurring 5 d apart. Peak
      corticosterone responses to hypoxia were reduced in vSUB-lesion animals,
      indicating an attenuation of HPA axis responsiveness. A subsequent study revealed
      that hyporesponsivity to hypoxia was evident in chamber-naive as well as chamber
      adapted animals, verifying that this effect was independent of previous
      experience in the testing environment. In contrast, the effects of vSUB lesions
      on corticosterone responses to the elevated plus maze exposure were substantially
      more circumspect, being limited to a slight increase in secretion at the 2-h
      poststress time point. The limited vSUB lesion-induced increase in the plasma
      corticosterone response to elevated plus maze exposure occurred despite an
      increased open-arm time in the maze, suggesting that lesions reduced anxiety-like
      behavior. In combination with previous studies, these data suggest that the vSUB
      has excitatory as well as inhibitory input into HPA axis responsivity, depending
      on the nature of the stressful stimulus, and suggest that behavioral and
      neuroendocrine responses to stressful or anxiogenic stimuli may be dissociable.

PMID- 15142983
TI  - Hormone-sensitive lipase deficiency in mouse islets abolishes neutral cholesterol
      ester hydrolase activity but leaves lipolysis, acylglycerides, fat oxidation, and
      insulin secretion intact.
AB  - Lipids are thought to serve as coupling factors in insulin secretion. Hormone
      sensitive lipase (HSL) is expressed in pancreatic beta-cells and could
      potentially regulate insulin secretion via mobilization of stored triglycerides.
      Here, we examined the impact of HSL deficiency on fuel metabolism and insulin
      secretion in mouse islets. Lack of HSL resulted in abrogation of neutral
      cholesterol ester hydrolase activity, whereas diglyceride lipase activity
      remained intact. Although glucose stimulates lipolysis in rat islets, elevation
      of glucose with or without addition of cAMP failed to increase lipolysis in mouse
      islets regardless of genotype, as indicated by release of glycerol from islets.
      Storage of lipids, assayed as total acylglycerides, was unaltered in HSL null
      islets, and oxidation of fatty acids or glucose was not different. The
      intracellular rise in Ca(2+) triggered by glucose and its subsequent oscillations
      was unaffected in HSL null islets. Accordingly, insulin secretion in static
      incubations of islets, in response to fuel- and nonfuel secretagogues, was in no
      instance significantly different between wild-type and HSL null mice. The lacking
      impact of HSL deficiency on insulin secretion may be attributed to the failure of
      insulin secretagogues to stimulate lipolysis. Consequently, a regulatory function
      of lipid mobilization in insulin secretion in the mouse appears unlikely.

PMID- 15142984
TI  - Promoter analysis of human corticotropin-releasing factor (CRF) type 1 receptor
      and regulation by CRF and urocortin.
AB  - We report the full genomic organization of the human gene for the corticotropin
      releasing factor (CRF) receptor type 1 (CRFR1), with complete mapping of exons 1
      14. The 5' flanking region (2.4 kb) of the gene encoding for human CRFR1 was
      isolated, sequenced, and characterized. Two major transcriptional start sites
      were determined at -265 and -238, relative to the ATG start site (+1). Transient
      expression of constructs containing sequentially deleted 5'-flanking sequences of
      CRFR1 fused to luciferase, revealed the minimal promoter sequence 370 bp in size,
      as shown by assays in neuroblastoma (SH-5YSY), teratocarcinoma (NT2), and
      adenocarcinoma (MCF 7) cell lines. CRF and UCN markedly increased promoter
      activity during transient CRFR1 expression studies. Similarly, CRF and UCN up
      regulate the endogenous CRFR1 at the mRNA level in NT2 and MCF 7 cells. To
      dissect further the mechanisms involved, we have used primary myometrial cells
      transfected with the CRFR1 promoter. CRF and UCN increased the promoter activity,
      an effect blocked by protein kinase (PK)A and PKC inhibitors. Both CRF and UCN
      cause a positive feedback effect in primary cultures of human pregnant myometrial
      cells, by increasing mRNA expression of CRFR1. This effect appears to be
      dependent on activation of both PKA and PKC by CRF, whereas UCN's effect was
      mediated solely via PKC activation. Collectively, our data suggest that the CRFR1
      gene is under the influence of both CRF and UCN, acting via distinct signaling
      pathways to create a positive feedback loop and regulate further the
      transcription of the receptor.

PMID- 15142985
TI  - Distinctive roles for prolactin and growth hormone in the activation of signal
      transducer and activator of transcription 5 in pancreatic islets of langerhans.
AB  - Although the beta-cells of the pancreatic islets of Langerhans express both
      prolactin (PRL) and GH receptors, we have observed that PRL is considerably more
      effective than GH in the up-regulation of islet function in vitro. This study
      examined whether differences in the activation of the Janus kinase 2/signal
      transducer and activator of transcription (STAT) 5 signaling pathway by these
      closely related receptors may be involved in this disparity. The activation of
      STAT5B by PRL was biphasic, with an initial peak within 30 min, a nadir between 1
      and 3 h, and prolonged activation after 4 h. In contrast, the response to GH was
      transient for 1 h. The importance of the long-term activation of STAT5B by PRL
      was supported by the similar dose response curves for STAT5B activation and the
      PRL-induced increases in insulin secretion and islet cell proliferation. Because
      the pulsatile secretion of GH affects its actions in other target tissues, the
      ability of pretreatment with either hormone to affect subsequent stimulation was
      also examined. Surprisingly, the response to PRL was inhibited by prior exposure
      for less than 3 h to either PRL or GH and disappeared with a longer pretreatment
      with either hormone. Similar to other tissues, the response to GH was inhibited
      by any length of prior exposure to GH. However, pretreatment with PRL had no
      effect. These experiments are the first demonstration of the transient
      desensitization of the PRL receptor by either PRL or GH pretreatment in any
      tissue and the desensitization of GH stimulation in islet cells. These
      observations provide insight into the mechanisms that regulate the
      desensitization of these receptors and, more importantly, allow the long-term
      activation of STAT5B by the PRL receptor. These results may apply to other
      members of the cytokine superfamily of receptors. We also demonstrate that the
      increase in islet cell proliferation required continuous stimulation with PRL,
      whereas the smaller effect with GH occurred with either continuous or pulsatile
      stimulation. In summary, this study demonstrates that islets are sensitive to the
      temporal pattern of stimulation by these hormones and provides a new basis for
      understanding their physiological roles in the regulation of islet function.

PMID- 15142986
TI  - Selective deletion of the Hnf1beta (MODY5) gene in beta-cells leads to altered
      gene expression and defective insulin release.
AB  - Hepatocyte nuclear factor 1alpha (HNF1alpha) and HNF1beta (or vHNF1) are closely
      related transcription factors expressed in liver, kidney, gut, and pancreatic
      beta-cells. Many HNF1 target genes are involved in carbohydrate metabolism. Human
      mutations in HNF1alpha or HNF1beta lead to maturity-onset diabetes of the young
      (MODY3 and MODY5, respectively), and patients present with impaired glucose
      stimulated insulin secretion. The underlying defect in MODY5 is not known.
      Analysis of HNF1beta deficiency in mice has not been possible because HNF1beta
      null mice die in utero. To examine the role of HNF1beta in glucose homeostasis,
      viable mice deleted for HNF1beta selectively in beta-cells (beta/H1beta-KO mice)
      were generated using a Cre-LoxP strategy. beta/H1beta-KO mice had normal growth,
      fertility, fed or fasted plasma glucose and insulin levels, pancreatic insulin
      content, and insulin sensitivity. However, beta/H1beta-KO mice exhibited impaired
      glucose tolerance with reduced insulin secretion compared with wild-type mice but
      preserved a normal insulin secretory response to arginine. Moreover, beta/H1beta
      KO islets had increased HNF1alpha and Pdx-1, decreased HNF4 mRNA levels, and
      reduced glucose-stimulated insulin release. These results indicate that HNF1beta
      is involved in regulating the beta-cell transcription factor network and is
      necessary for glucose sensing or glycolytic signaling.

PMID- 15142987
TI  - Chronic stress promotes palatable feeding, which reduces signs of stress:
      feedforward and feedback effects of chronic stress.
AB  - We suggested a new model of the effects of glucocorticoids (GCs) exerted during
      chronic stress, in which GCs directly stimulate activities in the brain while
      indirectly inhibiting activity in the hypothalamo-pituitary-adrenal (HPA) axis
      through their metabolic shifts in energy stores in the periphery. This study is
      an initial test of our model. In a 2 x 2 design, we provided ad lib access to
      calorically dense lard and sucrose (comfort food) + chow or chow alone, and
      repeatedly restrained half of the rats in each group for 5 d (3 h/d). We measured
      caloric intake, body weight, caloric efficiency, ACTH, corticosterone (B), and
      testosterone during the period of restraint and leptin, insulin, and fat depot
      weights, as well as hypothalamic corticotropin-releasing factor mRNA at the end
      of the period. We hypothesized that chronically restrained rats would exhibit a
      relative increase in comfort food ingestion and that these rats would have
      reduced HPA responses to repeated restraint. Although total caloric intake was
      reduced in both groups of restrained rats, compared with controls, the proportion
      of comfort food ingested increased in the restrained rats compared with their
      nonrestrained controls. Moreover, caloric efficiency was rescued in the stressed,
      comfort food group. Furthermore, ACTH and B responses to the repeated restraint
      bouts were reduced in the rats with access to comfort food. Corticotropin
      releasing factor mRNA was reduced in control rats eating comfort food compared
      with those eating chow, but there were no differences between the stressed
      groups. The results of this experiment tend to support our model of chronic
      effects of stress and GCs, showing a stressor-induced preference for comfort
      food, and a comfort-food reduction in activity of the HPA axis.

PMID- 15142988
TI  - Region-specific reduction in leptin-induced phosphorylation of signal transducer
      and activator of transcription-3 (STAT3) in the rat hypothalamus is associated
      with leptin resistance during pregnancy.
AB  - Leptin concentrations increase during pregnancy, but this does not prevent the
      pregnancy-induced increase in food intake, suggesting a state of leptin
      resistance. This study investigated the response to intracerebroventricular
      leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14
      pregnant rats received leptin (4 microg) or vehicle, then food intake was
      measured. Serial blood samples were collected in another group of rats to
      determine plasma leptin concentrations. Further groups of d-14 pregnant and
      nonpregnant rats were killed after leptin or vehicle treatment, and brains were
      collected. Hypothalamic nuclei were microdissected, and levels of signal
      transducer and activator of transcription (STAT)3 phosphorylation were measured
      using Western blot analysis. Fasting decreased leptin concentrations in both
      pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake
      in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition,
      there was no postfasting hyperphagic response in the pregnant rats. In the
      pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate
      nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared
      with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH
      during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and
      lateral hypothalamus was not different between pregnant and nonpregnant rats.
      These data indicate that pregnant rats become resistant to the satiety action of
      leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during
      pregnancy, specifically in the arcuate nucleus and VMH. These data support the
      hypothesis that pregnancy is a state of hypothalamic leptin resistance.

PMID- 15142989
TI  - Leptin-induced increase in leukemia inhibitory factor and its receptor by human
      endometrium is partially mediated by interleukin 1 receptor signaling.
AB  - Leptin and leukemia inhibitory factor (LIF) have been implicated as important
      mediators of implantation. The present study was designed to investigate whether
      leptin can directly regulate the expression of LIF and its receptor (LIF-R) in
      human endometrial cells and/or whether leptin-induced effects are linked to, or
      regulated in part by IL-1 signaling. Primary endometrial cells and endometrial
      epithelial cell lines (HES and Ishikawa cells) were cultured for 24-48 h in a
      medium containing insulin (5 microg/ml) and leptin (3, 10, and 62 nm) or IL-1beta
      (0.6, 3, and 10 nm) in the presence or absence of cytokines and/or receptor
      antagonists. The endpoints included phosphorylation of signal transducer and
      activator of transcription 3 (STAT3) and the relative levels of LIF, LIF-R, IL
      1beta, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type I (IL-1R tI) as
      determined by ELISA or Western blotting techniques. Leptin treatment increases
      the level of phosphorylated STAT3, LIF-R, and LIF. Leptin also increases the
      levels of IL-1 ligand, receptor, and antagonist as was previously reported.
      Blockade of OB-R with antibodies or with a specific OB-R inhibitor (leptin
      peptide antagonist-2) abrogated leptin-induced effects, suggesting that leptin
      binding to its receptor activates Janus kinase 2/STAT3 signaling. Treatment of
      endometrial cells with IL-1beta also results in elevated levels of LIF-R.
      Interestingly, the inhibition of IL-1R tI with a specific antibody or with IL-1Ra
      negatively affects both leptin-induced and IL-1-induced effects on LIF-R levels.
      Abnormal endometrial LIF expression has been associated with human infertility
      and leptin has profound effects on the levels of LIF, IL-1, and their cognate
      receptors in vitro. Thus, it is tempting to speculate that leptin's role in vivo
      could include the regulation of other key cytokines to be fundamental to
      endometrial receptivity during implantation (i.e. LIF and IL-1).

PMID- 15142991
TI  - Sexually dimorphic effects of prenatal stress on cognition, hormonal responses,
      and central neurotransmitters.
AB  - Exposure to stress during gestation results in physiological and behavioral
      alterations that persist into adulthood. This study examined the effects of
      prenatal stress on the postnatal expression of sexually differentiated cognitive,
      hormonal, and neurochemical profiles in male and female rats. Pregnant dams were
      subjected to restraint stress three times daily for 45 min during d 14-21 of
      pregnancy. The offspring of control and prenatally stressed dams were tested for
      anxiety-related and cognitive behaviors, stress and gonadal steroid hormone
      levels, as well as monoamines and metabolite levels in selected brain regions.
      Postnatal testosterone levels (measured at 1 and 5 d) did not differ between
      controls and prenatally stressed animals. In adulthood, the serum corticosterone
      response to stress was attenuated in prenatally stressed females, eliminating the
      sex difference normally observed in this parameter. Prenatally stressed females
      exhibited higher anxiety levels, evidenced by longer open field entry latencies.
      Prenatal stress had no effect on object recognition memory, but eliminated the
      advantage normally seen in the male performance of a spatial memory task.
      Neurochemical profiles of prenatally stressed females were altered toward the
      masculine phenotype in the prefrontal cortex, amygdala, and hippocampus. Thus,
      prenatal stress altered subsequent cognitive, endocrine, and neurochemical
      responses in a sex-specific manner. These data reinforce the view that prenatal
      stress affects multiple aspects of brain development, interfering with the
      expression of normal behavioral, neuroendocrine, and neurochemical sex
      differences. These data have implications for the effects of prenatal stress on
      the development of sexually dimorphic endocrine and neurological disorders.

PMID- 15142990
TI  - Tumor necrosis factor alpha stimulates MUC1 synthesis and ectodomain release in a
      human uterine epithelial cell line.
AB  - Regulation of MUC1 expression and removal is a salient feature of embryo
      implantation, bacterial clearance, and tumor progression. In some species, embryo
      implantation is accompanied by a transcriptional decline in uterine epithelial
      expression of MUC1. In other species, MUC1 is locally removed at blastocyst
      attachment sites, suggesting a proteolytic activity. Previously, we demonstrated
      that MUC1 is proteolytically released from the surface of a human uterine
      epithelial cell line, HES, and identified TNFalpha converting enzyme/a
      disintegrin and metalloprotease 17 as a constitutive and phorbol ester-stimulated
      MUC1 sheddase. The aims of the current study were to test the ability of soluble
      factors elevated during the periimplantation interval in vivo to stimulate
      ectodomain shedding of MUC1 from HES uterine epithelial cells and to characterize
      the nature of this proteolytic activity(ies). We identified TNFalpha as a
      prospective endogenous stimulus of MUC1 ectodomain release and of MUC1 and
      TNFalpha converting enzyme/a disintegrin and metalloprotease 17 expression.
      Moreover, we established that TNFalpha-stimulated MUC1 shedding occurs
      independently of increased de novo protein synthesis and demonstrated that the
      TNFalpha-induced increase in MUC1 gene expression is mediated through the kappaB
      site in the MUC1 promoter. Finally, we determined that the TNFalpha-sensitive
      MUC1 sheddase is inhibited by the metalloprotease inhibitor, TNFalpha protease
      inhibitor (TAPI), and the endogenous tissue inhibitor of metalloprotease-3.
      Collectively, these studies provide the initial in vitro characterization of a
      putative physiological stimulus of MUC1 ectodomain release and establish the
      nature of the metalloproteolytic activity(ies) involved.

PMID- 15142992
TI  - The effects of estrogen on the expression of genes underlying the differentiation
      of somatic cells in the murine gonad.
AB  - Estrogen (17beta-estradiol, E2)-deficient aromatase knockout (ArKO) mice develop
      Sertoli and Leydig cells at puberty. We hypothesized that estrogen, directly or
      indirectly, regulates genes responsible for somatic cell differentiation and
      steroidogenesis. ArKO ovaries expressed estrogen receptors alpha and beta, and LH
      receptor, indices of estrogen responsiveness in the ovary. Wild-type (Wt) and
      ArKO mice received either E2 or placebo for 3 wk, from 7-10 wk of age. E2
      decreased serum FSH and LH and increased uterine weights of 10-wk-old ArKO mice.
      We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9);
      three upstream transcription factors, liver receptor homolog-1 (Lrh-1),
      steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia
      congenital critical region on the X chromosome gene 1; and one downstream factor,
      Mullerian-inhibiting substance. Placebo-treated ArKO ovaries have increased Sox9
      (15-fold; P < 0.001), Mullerian-inhibiting substance (2.9-fold), Lrh-1 (7.7
      fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical
      region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk.
      Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T
      levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had
      increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and
      17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk.
      E2 treatment for 3 wk improved the ovarian phenotype, decreased development of
      Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic
      enzymes in ArKO ovaries, and induced ovulation in some cases. In conclusion, the
      expression of the genes regulating somatic cell differentiation is directly or
      indirectly responsive to estrogen.

PMID- 15142994
TI  - Defining poor ovarian response during IVF cycles, in women aged <40 years, and
      its relationship with treatment outcome.
AB  - BACKGROUND: Poor ovarian response limits IVF success but assessing interventions
      is difficult because of the wide variation in definition. This study attempts to
      derive objective definitions of poor response. METHODS: A retrospective study of
      a consecutive series of 1190 patients aged <40 years undergoing their first
      IVF/ICSI cycle was undertaken. Factors adversely affecting implantation,
      including advanced female age, were excluded. Clinical outcome in cycles reaching
      oocyte retrieval (n = 1036) were evaluated with respect to gonadotrophin dose
      used and oocyte number. Cancelled cycles (n = 154) were analysed in relation to
      the stimulation dose at cancellation and outcome of their subsequent cycle.
      RESULTS: Cycle cancellation for patients on >/=300 IU FSH/day compared to those
      on a lower dose was associated with a significantly worse outcome in the
      subsequent cycle. If <3000 IU FSH/cycle were administered, clinical pregnancy
      rates remained favourable if <4 eggs were recovered (29 versus 33% for >/=5
      eggs). By contrast, if >/=3000 IU FSH was required, the pregnancy rate was 25% if
      >/=5 eggs were recovered but declined to 7% if <4 were obtained. CONCLUSIONS:
      Definitions of poor response should include the degree of ovarian stimulation
      used. A low oocyte number is only detrimental if the cumulative dose is >3000 IU
      FSH. Cancellation at >/=300 IU FSH/day is associated with a significantly worse
      prognosis and could define poor response.

PMID- 15142993
TI  - ICSI using testicular sperm in male hypogonadotrophic hypogonadism unresponsive
      to gonadotrophin therapy.
AB  - BACKGROUND: The aim of this study was to assess the use of testicular sperm for
      ICSI in azoospermic men with hypogonadotrophic hypogonadism unresponsive to
      gonadotrophin therapy. METHODS: Fifteen patients with hypogonadotrophic
      hypogonadism who remained azoospermic after hormonal treatment underwent
      testicular sperm extraction (TESE) and ICSI. These men were recruited from the
      Egyptian IVF centre over a period of 4 years. All patients were given 75 IU hMG
      thrice weekly and 5000 IU hCG once or twice weekly for >/=6 months prior to
      attempting ICSI/TESE. RESULTS: In 11 out of 15 patients (73%), sperm could be
      retrieved from testicular tissue and were used for ICSI. Two chemical pregnancies
      resulted but no clinical pregnancies. Nine patients continued gonadotrophin
      therapy for another 6 months. Sperm appeared in the ejaculate of three of them.
      The remaining six patients underwent another ICSI cycle, one using cryopreserved
      sperm and five underwent a second TESE. One chemical pregnancy and three clinical
      pregnancies were established. One ongoing, one singleton and one twin pregnancies
      resulted in the delivery of three healthy babies. In total, of 17 ICSI cycles
      performed using testicular sperm retrieval, the fertilization rate was 41.7% and
      the cumulative pregnancy rate was 20%. CONCLUSIONS: The use of testicular sperm
      for ICSI is a treatment option that can be offered to azoospermic males with
      hypogonadotrophic hypogonadism either not responding or reluctant to continue
      hormonal treatment. However, prolonged hormonal treatment may improve TESE/ICSI
      results.

PMID- 15142995
TI  - Obesity is associated with increased risk of first trimester and recurrent
      miscarriage: matched case-control study.
AB  - BACKGROUND: Obesity has become a major health problem worldwide and is also
      associated with adverse pregnancy outcome. The aim of this study was to assess
      the impact of obesity on the risk of miscarriage in the general public. METHODS:
      This was a nested case-control study. The study population was identified from a
      maternity database. Obese [body mass index (BMI) >30 kg/m2] women were compared
      with an age-matched control group with normal BMI (19-24.9 kg/m2). Only
      primiparous women were included in the study to avoid including the subject more
      than once, and to be able to correctly identify recurrent miscarriages. The
      prevalence of a previous history of early (6-12 weeks gestation), late (12-24
      weeks gestation) and recurrent early miscarriages (REM) (more than three
      successive miscarriages <12 weeks) was compared between the two groups. RESULTS:
      A total of 1644 obese and 3288 age-matched normal weight controls with a mean age
      of 26.6 years [95% confidence interval (CI) 26.5-26.7] were included in the
      study. The risks of early miscarriage and REM were significantly higher among the
      obese patients (odds ratios 1.2 and 3.5, 95% CI 1.01-1.46 and 1.03-12.01,
      respectively; P = 0.04, for both]. CONCLUSIONS: Obesity is associated with
      increased risk of first trimester and recurrent miscarriage.

PMID- 15142996
TI  - Changes in gonadal steroid receptors in the cardinal ligaments of prolapsed
      uteri: immunohistomorphometric data.
AB  - BACKGROUND: The precise mechanism of uterine prolapse is poorly understood. This
      immunohistochemical study was performed on paraffin-embedded sections of the
      cardinal ligaments in an attempt to evaluate the differential expression of
      gonadal steroid receptors in human cardinal ligaments of prolapsed uteri compared
      with non-prolapsed controls. METHODS: Specimens from women with pelvic organ
      prolapse (POP) stage III (n = 33), together with the appropriate controls (n =
      25), were stained for estrogen receptor alpha (ERalpha), ERbeta, progesterone
      receptor (PR), androgen receptor (AR) and Ki-67. The control materials were
      samples of the cardinal ligaments obtained from pre- and post-menopausal women
      with no prolapse, who were not using hormonal therapy. RESULTS The prolapsed
      ligaments expressed 1.5-2.5 times more ERalpha-positive cells (statistically
      significant in post-menopausal women not taking HRT, P < 0.001), a 3-4 times
      greater percentage of AR-positive cells (P = 0.004 and P = 0.008 in pre
      menopausal and post-menopausal women not taking HRT, respectively) and twice the
      percentage of PR-positive cells (statistically significant in the pre-menopausal
      group, P = 0.03) compared with the no prolapse group. Expression of ERbeta was
      twice as high in the ligaments of pre-menopausal women with no prolapse compared
      with those with prolapse (P = 0.02), and no significant difference was found in
      the post-menopausal groups. The use of HRT was significantly associated with low
      AR and high PR expression. Ki-67 expression was not detected in these specimens.
      CONCLUSIONS: The clearly discernible levels of expression of ERalpha, ERbeta, AR
      and PR in the prolapsed cardinal ligaments may suggest a relationship to the
      process of tissue stretch 'trauma', rather than an effect of the menopausal
      status, HRT use or cell proliferation. The use of HRT in post-menopausal women
      appears to offset some of the changes observed with the prolapse.

PMID- 15142997
TI  - A prospective, randomized study: day 3 versus hatching blastocyst stage.
AB  - BACKGROUND: Recently, advances in human IVF-embryo transfer (ET) have been
      reported using sequential media and blastocyst stage ET. In our previous report,
      using a prospective, randomized study, no advantage was found using the
      blastocyst stage ET compared with day 3 ET. This study was performed in order to
      evaluate implantation and pregnancy rates of hatching blastocyst stage ET
      compared with conventional day 3 ET. METHODS AND RESULTS: A total of 480 patient
      cycles were evaluated using a prospective, randomized study. The pregnancy rate
      and implantation rate were compared between the day 3 ET (n = 240) and hatching
      blastocyst stage ET (Hat ET; n = 240). The Hat ET group had a pregnancy rate of
      29.3% (55 out of 188) and an implantation rate of 21.4% (67 out of 313). The day
      3 ET group had a pregnancy rate of 29.2% (70 out of 240) and an implantation rate
      of 19.1% (93 out of 488). In the Hat ET group, the pregnancy rate, implantation
      rate and ongoing pregnancy rate of day 5 ET and day 6 ET were all higher than the
      respective rates in the day 7-9 ET group. CONCLUSION: We found that the pregnancy
      rate and implantation rate of ET with hatching stage blastocysts had no advantage
      compared with the conventional day 3 ET.

PMID- 15142998
TI  - Four zona pellucida glycoproteins are expressed in the human.
AB  - BACKGROUND: The zona pellucida (ZP) is an extracellular glycoprotein matrix which
      surrounds all mammalian oocytes. Recent data have shown the presence of four
      human zona genes (ZP1, ZP2, ZP3 and ZPB). The aim of the study was to determine
      if all four ZP proteins are expressed and present in the human. METHODS: cDNA
      derived from human oocytes were used to amplify by PCR the four ZP genes. In
      addition, isolated native human ZP were heat-solubilized, trypsin-digested and
      subjected to tandem mass spectrometry (MS/MS). RESULTS: All four genes were
      expressed and the respective proteins present in the human ZP. Moreover, a
      bioinformatics approach showed that the mouse ZPB gene, although present, is
      likely to encode a non-functional protein. CONCLUSIONS: Four ZP genes are
      expressed in human oocytes (ZP1, ZP2, ZP3 and ZPB) and preliminary data show that
      the four corresponding ZP proteins are present in the human ZP. Therefore, this
      is a fundamental difference with the mouse model

PMID- 15142999
TI  - Comparison of the aneuploidy frequency in embryos derived from testicular sperm
      extraction in obstructive and non-obstructive azoospermic men.
AB  - BACKGROUND: The use of ICSI has been a major breakthrough in the treatment of
      male infertility. Even azoospermic patients with focal spermatogenesis in the
      testis (not sufficient to spill over into the ejaculate) may benefit from the
      technique. Previous reports suggest a higher pregnancy rate after ICSI treatment
      in patients with obstructive azoospermia (OA) compared to their non-obstructive
      azoospermia (NOA) counterparts, which could be due to a higher aneuploidy
      frequency in the embryos of the latter group. We therefore conducted a
      prospective cohort study to compare the aneuploidy frequency of the screened
      embryos between the two groups. METHODS: From May 2001 until September 2003, we
      offered couples with an OA or NOA partner ICSI in combination with
      preimplantation genetic diagnosis for aneuploidy screening. RESULTS: No
      difference in age (30.6 and 33.5 years) or stimulation parameters was observed
      between the two groups; 53 and 60% of the embryos were abnormal in the NOA and OA
      groups respectively (P = not significant). CONCLUSIONS: The aneuploidy frequency
      in embryos obtained from NOA as well as OA men is similar and very high, despite
      the young age of their female partners.

PMID- 15143000
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.
AB  - The purpose of this announcement is to effect the valid publication of the
      following new names and new combinations under the procedure described in the
      Bacteriological Code (1990 Revision). Authors and other individuals wishing to
      have new names and/or combinations included in future lists should send three
      copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial
      Office for confirmation that all of the other requirements for valid publication
      have been met. It is also a requirement of IJSEM and the ICSP that authors of new
      species, new subspecies and new combinations provide evidence that types are
      deposited in two recognized culture collections in two different countries (i.e.
      documents certifying deposition and availability of type strains). It should be
      noted that the date of valid publication of these new names and combinations is
      the date of publication of this list, not the date of the original publication of
      the names and combinations. The authors of the new names and combinations are as
      given below, and these authors' names will be included in the author index of the
      present issue and in the volume author index. Inclusion of a name on these lists
      validates the publication of the name and thereby makes it available in
      bacteriological nomenclature. The inclusion of a name on this list is not to be
      construed as taxonomic acceptance of the taxon to which the name is applied.
      Indeed, some of these names may, in time, be shown to be synonyms, or the
      organisms may be transferred to another genus, thus necessitating the creation of
      a new combination.

PMID- 15143002
TI  - Petrobacter succinatimandens gen. nov., sp. nov., a moderately thermophilic,
      nitrate-reducing bacterium isolated from an Australian oil well.
AB  - A novel Gram-negative, aerobic and moderately thermophilic bacterium, strain
      4BON(T), was isolated from a non-water-flooded Australian terrestrial oil
      reservoir. Cells were non-spore-forming straight rods, which were motile by means
      of a polar flagellum. The optimum growth conditions were 55 degrees C, pH 6.9 and
      0.5 % NaCl. Strain 4BON(T) was oxidase- and catalase-positive; it grew on
      fumarate, pyruvate, succinate, formate, ethanol and yeast extract in the presence
      of oxygen or nitrate as terminal electron acceptor. Nitrate was reduced to
      nitrous oxide. The DNA G+C content of the strain was 58.6 mol%. The closest
      phylogenetic relative of strain 4BON(T) was Hydrogenophilus thermoluteolus
      (similarity of 91.8 %), of the beta-Proteobacteria. As strain 4BON(T) is
      physiologically and phylogenetically different from H. thermoluteolus, it is
      proposed that it be assigned to a novel species of a novel genus, Petrobacter
      succinatimandens gen. nov., sp. nov. The type strain is 4BON(T) (=DSM
      15512(T)=CIP 107790(T)).

PMID- 15143003
TI  - Phylogenetic relationships of the genera Stella, Labrys and Angulomicrobium
      within the 'Alphaproteobacteria' and description of Angulomicrobium amanitiforme
      sp. nov.
AB  - The unusually shaped bacteria of the genera Stella, Labrys and Angulomicrobium
      have been described based on their cell morphology and biochemistry. However,
      their phylogenetic relationships remain unresolved. An earlier study that was
      based on 5S rRNA gene sequences placed the genus Stella within the
      'Alphaproteobacteria'. In the present report, polar lipids and 16S rRNA genes of
      the type strains of the two species in the genus Stella, Stella humosa DSM
      5900(T) and Stella vacuolata DSM 5901(T), are studied, as well as the type
      strains of the monospecific genera Labrys (Labrys monachus VKM B-1479(T)) and
      Angulomicrobium (Angulomicrobium tetraedrale DSM 5895(T)). It was found that the
      genus Stella belongs to the order Rhodospirillales in the family
      Rhodospirillaceae, and not to the Acetobacteraceae. Whilst the position of the
      genus Angulomicrobium in the family Hyphomicrobiaceae was confirmed, the genus
      Labrys could not be placed into any known family, but was adjacent to the family
      'Beijerinckiaceae'. In addition, data were obtained for strain VKM B-1336, which
      was shown not to belong to the genus Angulomicrobium, and strain NCIMB 1785(T)
      (=DSM 15561(T)), for which the name Angulomicrobium amanitiforme sp. nov. is
      proposed.

PMID- 15143001
TI  - Delineation of the genus Actinobacillus by comparison of partial infB sequences.
AB  - A 426 bp fragment of infB, a housekeeping gene that encodes translation
      initiation factor 2, was sequenced from 59 clinical isolates and type strains of
      Actinobacillus species and sequences were compared. Partial sequences of 16S rRNA
      genes were also obtained. By comparing infB sequences, Actinobacillus
      pleuropneumoniae, Actinobacillus equuli, Actinobacillus suis, Actinobacillus
      ureae, Actinobacillus arthritidis, Actinobacillus hominis and two unnamed
      genomospecies showed more than 85 % similarity to the type strain of the type
      species of the genus, Actinobacillus lignieresii. The taxonomic position of
      Actinobacillus capsulatus was unresolved; this species is more remotely related
      to A. lignieresii. The two species A. lignieresii and A. pleuropneumoniae could
      not be clearly separated by infB sequence analysis. The phylogeny of the genus
      Actinobacillus based on infB analysis was essentially congruent with
      relationships inferred from 16S rRNA sequence comparisons and DNA hybridization
      studies. Discrepancies were encountered with single strains or taxa at the
      periphery of the genus. Greater intraspecies variation was observed with infB
      sequences than with 16S rRNA gene sequences, with notable exceptions. The
      apparent subdivision of some species by 16S rRNA analysis was most likely caused
      by RNA operon heterogeneity.

PMID- 15143004
TI  - Mycobacterium saskatchewanense sp. nov., a novel slowly growing scotochromogenic
      species from human clinical isolates related to Mycobacterium interjectum and
      Accuprobe-positive for Mycobacterium avium complex.
AB  - A pigmented, slowly growing Mycobacterium avium complex AccuProbe-positive
      organism was isolated from the sputum and pleural fluid of a 72-year-old female
      with bronchiectasis. The unusual morphology of the organism prompted further
      identification by 16S rRNA gene sequencing, revealing a perfect identity with
      previously uncharacterized strain Mycobacterium sp. MCRO 8 (GenBank accession no.
      X93034), with the closest established species by 16S rDNA analysis being
      Mycobacterium interjectum. HPLC of the organism corresponded to previously
      obtained patterns identified as M. interjectum-like and, upon sequence evaluation
      of a selection of strains with a similar profile, more were subsequently
      identified as MCRO 8. A total of 16 strains isolated from human respiratory
      samples were evaluated in the characterization of this novel species, for which
      the name Mycobacterium saskatchewanense sp. nov. is proposed. The type strain is
      strain 00-250(T) (=ATCC BAA-544(T)=DSM 44616(T)=CIP 108114(T)).

PMID- 15143005
TI  - Reinekea marinisedimentorum gen. nov., sp. nov., a novel gammaproteobacterium
      from marine coastal sediments.
AB  - A Gram-negative, oxidase- and catalase-positive, rod-shaped bacterium, designated
      strain KMM 3655(T), was isolated from a coastal marine sediment sample. The novel
      bacterium required sodium ions for growth and grew between 0.5 and 5 % NaCl and
      at 4-37 degrees C, but not at 40 degrees C. It reduced nitrate, formed acids from
      glucose under aerobic and anaerobic conditions, utilized a limited spectrum of
      organic substrates and did not produce gelatinase, caseinase, amylase or
      chitinase. The major isoprenoid quinone was Q8. Polar lipids consisted of
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol and an unknown phospholipid. Fatty acid analysis of strain
      KMM 3655(T) revealed C(16 : 0), C(16 : 1)omega7c and C(18 : 1)omega7c as
      predominant components. The G+C content of the DNA was 51.1 mol%. Phylogenetic
      analysis of the 16S rDNA sequence placed the new isolate within the gamma
      Proteobacteria as a separate deep branch, with about 90 % sequence similarity to
      representatives of the genus Oceanospirillum and other remotely related genera.
      Combined phylogenetic and physiological data show that the new marine sediment
      isolate, KMM 3655(T), represents a novel genus and species, for which the name
      Reinekea marinisedimentorum gen. nov., sp. nov. is proposed. The type strain is
      KMM 3655(T) (=DSM 15388(T)).

PMID- 15143006
TI  - Kordia algicida gen. nov., sp. nov., an algicidal bacterium isolated from red
      tide.
AB  - A bacterium (named OT-1(T)) that showed algicidal activity was isolated from sea
      water of Masan Bay, Korea, during an outbreak of red tide. Phylogenetic analysis
      based on 16S rDNA sequences showed that the isolate formed a distinct phyletic
      lineage within the family Flavobacteriaceae of the Cytophaga-Flavobacterium
      Bacteroides group. No species with a validly published name showed >/=93 % 16S
      rRNA gene sequence similarity to strain OT-1(T). The isolate had major amounts of
      iso-branched and 3-hydroxy iso-branched fatty acids and menaquinone 6 and a DNA
      G+C content of 34 mol%; these chemotaxonomic characters also supported the
      placement of the organism in the family Flavobacteriaceae. The strain was Gram
      negative, yellow-pigmented, non-motile, non-gliding, flexirubin-negative,
      strictly aerobic, catalase-negative, oxidase-positive and halophilic. Na(+),
      Ca(2+) and Mg(2+) ions were obligately required for growth. The strain utilized
      various sugars as sole carbon sources and degraded gelatin, skimmed milk and
      starch. Several phenotypic characters can be used to differentiate the test
      strain from phylogenetically related marine bacterial genera. On the basis of
      polyphasic evidence, it is proposed that strain OT-1(T) should be assigned to the
      family Flavobacteriaceae as Kordia algicida gen. nov., sp. nov. The type strain
      is OT-1(T) (=KCTC 8814P(T)=NBRC 1000336(T)).

PMID- 15143007
TI  - Phylogeny of the ring-forming bacterium Arcicella aquatica gen. nov., sp. nov.
      (ex Nikitin et al. 1994), from a freshwater neuston biofilm.
AB  - Arcicella aquatica NO-502(T), obtained from a neuston film on a freshwater lake
      and belonging to the phylum Bacteroidetes, is characterized by ring-forming
      cells. The bacterium is a strict aerobe, with optimal growth between 28 and 30
      degrees C. Carbohydrates, but no organic acids or amino acids, are used as
      substrates. The G+C content of strain NO-502(T) is 34.5 mol%; its genome size is
      2.9 x 10(9) Da. The genus Arcicella and its type species Arcicella aquatica (type
      strain NO-502(T)=LMG 21963(T)=CIP 107990(T)) are proposed, and descriptions of
      this genus and species are given.

PMID- 15143008
TI  - Reclassification of Cellulosimicrobium variabile Bakalidou et al. 2002 as
      Isoptericola variabilis gen. nov., comb. nov.
AB  - As already depicted in the original publication, the type strain of the species
      Cellulosimicrobium variabile Bakalidou et al. 2002, DSM 10177(T), does not
      cluster unambiguously with the type species, Cellulosimicrobium cellulans DSM
      43879(T), in phylogenetic analysis. Strain DSM 10177(T) is moderately related to
      the recently described species Xylanimonas cellulosilytica, Promicromonospora
      pachnodae and Xylanibacterium ulmi, forming a lineage that branches between C.
      cellulans and members of the genus Promicromonospora in most dendrograms
      generated on the basis of different algorithms and reference strains. The type
      strains of the two Cellulosimicrobium species resemble each other in morphology,
      composition of fatty acids, DNA G+C content, phospholipids and the presence of
      lysine in position 3 of the peptide subunit of peptidoglycan. However, the two
      strains differ from each other in cell-wall sugars and in the amino acid
      composition of the A4alpha-type peptidoglycan, which contains serine and aspartic
      acid in C. cellulans, whereas only aspartic acid is present in the interpeptide
      bridge of C. variabile. This type is also present in Xylanimonas cellulosilytica
      XIL07(T), but not in the neighbouring species P. pachnodae DSM 12657(T), which
      exhibits the L-lys-L-ser-D-Glu type. On the basis of distinct phylogenetic
      position and the amino acid composition of peptidoglycan, a novel genus and
      combination for C. variabile, Isoptericola variabilis gen. nov., comb. nov., is
      proposed.

PMID- 15143009
TI  - Proposal to accommodate Burkholderia cepacia genomovar VI as Burkholderia dolosa
      sp. nov.
AB  - Phenotypic and genotypic studies revealed new tools for differentiating
      Burkholderia cepacia genomovar VI from Burkholderia multivorans and other B.
      cepacia-complex species. Hence, the name Burkholderia dolosa sp. nov. is
      proposed, with LMG 18943(T) (=CCUG 47727(T)) as the type strain. B. dolosa can be
      differentiated from other B. cepacia-complex bacteria by its inability to
      assimilate tryptamine, azelaic acid and salicin and by its failure to grow on the
      B. cepacia-selective medium PCAT. Both 16S rDNA and recA RFLP analysis revealed
      unique B. dolosa restriction patterns. In addition, new 16S rDNA- and recA-based
      PCR assays allowed its specific identification.

PMID- 15143010
TI  - Agarivorans albus gen. nov., sp. nov., a gamma-proteobacterium isolated from
      marine animals.
AB  - Six bacterial strains were isolated from healthy marine organisms that were
      collected from the coast of the Kanto area in Japan. Phylogenetic analysis based
      on 16S rDNA sequence similarity showed that the six isolates formed a separate
      cluster in the gamma-Proteobacteria and were related to the genera Alteromonas
      and Glaciecola (<91.6 % similarity). The isolates were related closely to each
      other (DNA-DNA reassociation values of 74-93 %). The isolates had a polar
      flagellum and were Gram-negative, mesophilic, strictly aerobic rods that required
      salt for growth. Distinct phenotypic features of this group included the ability
      to hydrolyse agar and white pigmentation of colonies. The DNA G+C content of the
      isolates was 48-50 mol%. The major quinone was Q-8. Phenotypic characteristics of
      the isolates differed from those of members of the genera Alteromonas and
      GLACIECOLA: The name Agarivorans albus gen. nov., sp. nov. is proposed for the
      six isolates; the type strain is MKT 106(T) (=IAM 14998(T)=LMG 21761(T)).

PMID- 15143011
TI  - Legionella drancourtii sp. nov., a strictly intracellular amoebal pathogen.
AB  - A Legionella-like amoebal pathogen (LLAP), formerly named LLAP12(T), was
      characterized on the basis of microscopic appearance, staining characteristics,
      growth in Acanthamoeba polyphaga at different temperatures, DNA G+C content,
      serological cross-reactivity and 16S rRNA and macrophage infectivity potentiator
      (mip) gene sequence analysis. LLAP12(T) was found to be a motile, Gram-negative
      bacterium that grew within cytoplasmic vacuoles in infected amoebae. The
      infecting bacteria induced lysis of their amoebal hosts and time taken to do so
      was dependent on incubation temperature. Recovery of LLAP12(T) from amoebae onto
      axenic media could not be achieved. Phylogenetic analysis of LLAP12(T), based on
      16S rRNA and mip gene sequence analysis, indicated that it lay within the
      radiation of the Legionellaceae and that it clustered specifically with
      Legionella lytica and Legionella rowbothamii. The divergence observed between
      LLAP12(T) and these two species was of a degree equal to, or greater than, that
      observed between other members of the family. In support of this delineation,
      LLAP12(T) was found not to cross-react serologically with any other Legionella
      species. The mip and 16S rRNA gene sequence-based analyses also indicated that
      LLAP12(T) was related very closely to two other previously identified LLAP
      isolates, LLAP4 and LLAP11. Taken together, these results support the proposal of
      LLAP12(T) as the type strain of Legionella drancourtii sp. nov.

PMID- 15143012
TI  - Formosa algae gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae.
AB  - Four light-yellow-pigmented, Gram-negative, short-rod-shaped, non-motile isolates
      were obtained from enrichment culture during degradation of the thallus of the
      brown alga Fucus evanescens. The isolates studied were chemo-organotrophic,
      alkalitolerant and mesophilic. Polar lipids were analysed and
      phosphatidylethanolamine was the only phospholipid identified. The predominant
      cellular fatty acids were 15 : 0, i15 : 0, ai15 : 0, i15 : 1 and 15 : 1(n-6). The
      DNA G+C contents of the four strains were 34.0-34.4 mol%. The level of DNA
      relatedness of the four isolates was conspecific (88-98 %), indicating that they
      belong to the same species. The 16S rDNA sequence of strain KMM 3553(T) was
      determined. Phylogenetic analysis revealed that KMM 3553(T) formed a distinct
      phyletic line in the phylum Bacteroidetes, class Flavobacteria in the family
      Flavobacteriaceae and that, phylogenetically, this strain could be placed almost
      equidistant from the genera Gelidibacter and Psychroserpens (16S rRNA gene
      sequence similarities of 94 %). On the basis of significant differences in
      phenotypic and chemotaxonomic characteristics, it is suggested that the isolates
      represent a novel species in a new genus; the name Formosa algae gen. nov., sp.
      nov. is proposed. The type strain is KMM 3553(T) (=CIP 107684(T)).

PMID- 15143013
TI  - Psychrophilic pseudomonads from Antarctica: Pseudomonas antarctica sp. nov.,
      Pseudomonas meridiana sp. nov. and Pseudomonas proteolytica sp. nov.
AB  - Thirty-one bacteria that belonged to the genus Pseudomonas were isolated from
      cyanobacterial mat samples that were collected from various water bodies in
      Antarctica. All 31 isolates were psychrophilic; they could be divided into three
      groups, based on their protein profiles. Representative strains of each of the
      three groups, namely CMS 35(T), CMS 38(T) and CMS 64(T), were studied in detail.
      Based on 16S rRNA gene sequence analysis, it was established that the strains
      were related closely to the Pseudomonas fluorescens group. Phenotypic and
      chemotaxonomic characteristics further confirmed their affiliation to this group.
      The three strains could also be differentiated from each other and the closely
      related species Pseudomonas orientalis, Pseudomonas brenneri and Pseudomonas
      migulae, based on phenotypic and chemotaxonomic characteristics and the level of
      DNA-DNA hybridization. Therefore, it is proposed that strains CMS 35(T) (=MTCC
      4992(T)=DSM 15318(T)), CMS 38(T) (=MTCC 4993(T)=DSM 15319(T)) and CMS 64(T)
      (=MTCC 4994(T)=DSM 15321(T)) should be assigned to novel species of the genus
      Pseudomonas as Pseudomonas antarctica sp. nov., Pseudomonas meridiana sp. nov.
      and Pseudomonas proteolytica sp. nov., respectively.

PMID- 15143014
TI  - Halomonas boliviensis sp. nov., an alkalitolerant, moderate halophile isolated
      from soil around a Bolivian hypersaline lake.
AB  - Halomonas boliviensis sp. nov. is proposed for two moderately halophilic,
      psychrophilic, alkalitolerant bacteria, LC1(T) (=DSM 15516(T)=ATCC BAA-759(T))
      and LC2 (=DSM 15517=ATCC BAA-760), both of which were isolated from a soil sample
      around the lake Laguna Colorada, located at 4300 m above sea level in the south
      west region of Bolivia. The bacteria are aerobic, motile, Gram-negative rods that
      produce colonies with a cream pigment. Moreover, they are heterotrophs that are
      able to utilize various carbohydrates as carbon sources. The organisms reduce
      nitrate and show tryptophan deaminase activity. The genomic DNA G+C contents were
      51.4 mol% for isolate LC1(T) and 52.6 mol% for isolate LC2. Based on 16S rDNA
      sequence analysis, isolates LC1(T) and LC2 were identified as members of the
      genus Halomonas and clustered closely with Halomonas variabilis DSM 3051(T) and
      Halomonas meridiana DSM 5425(T). However, DNA-DNA relatedness between the new
      isolates and the closest related Halomonas species was low.

PMID- 15143015
TI  - Streptomyces hebeiensis sp. nov.
AB  - A novel actinomycete strain, YIM 001(T), was isolated from a soil sample
      collected from Hebei province, People's Republic of China. The strain was
      characterized by white to grey aerial mycelium. Long spore chains, borne on the
      aerial mycelium, were straight to Rectiflexibiles; the spore chains were composed
      of non-motile and coccoid spores with a warty surface. The cell wall of strain
      YIM 001(T) contained LL-diaminopimelic acid (A(2)pm) and traces of meso-A(2)pm.
      Whole-cell hydrolysates contained mainly glucose and small amounts of xylose,
      galactose and arabinose. The menaquinones were MK-9(H(4)) (4.6 %), MK-9(H(6)) (60
      %), MK-9(H(8)) (30.7 %) and MK-9(H(10)) (4.7 %). Phosphatidylethanolamine was the
      diagnostic phospholipid. The DNA G+C content of strain YIM 001(T) was 71.4 mol%.
      Phylogenetic analysis indicated that strain YIM 001(T) belongs to the genus
      Streptomyces. Based on its phenotypic and genotypic characteristics, strain YIM
      001(T) (=CCTCC AA 203005(T)=CIP 107974(T)=DSM 41837(T)) is proposed as the type
      strain of a novel species, Streptomyces hebeiensis sp. nov.

PMID- 15143016
TI  - Halomonas ventosae sp. nov., a moderately halophilic, denitrifying,
      exopolysaccharide-producing bacterium.
AB  - Halomonas ventosae sp, nov. includes three moderately halophilic,
      exopolysaccharide-producing strains isolated from saline soils in Jaen (south
      eastern Spain). These strains can grow anaerobically using either nitrate or
      nitrite as terminal electron acceptor and hydrolyse both tyrosine and
      phenylalanine. Their G+C content varies between 72.6 and 74.3 mol%. The
      affiliation of the isolates with the genus Halomonas was confirmed by 16S rRNA
      gene sequence comparison. DNA-DNA hybridization shows 70.4-82.7 % relatedness
      among the three strains. Nevertheless, their relatedness is less than 43 %
      compared to related reference strains. The proposed type strain for Halomonas
      ventosae is strain Al12(T) (=CECT 5797(T)=DSM 15911(T)). It grows best at 8 %
      (w/v) sea salts and requires the presence of Na(+). Its major fatty acids are 18
      : 1 omega7c, 16 : 0, 16 : 1 omega7c, and 15 : 0 iso 2-OH. The predominant
      respiratory lipoquinone found in strain Al12(T) is ubiquinone with nine isoprene
      units (Q-9).

PMID- 15143018
TI  - Jeotgalicoccus pinnipedialis sp. nov., from a southern elephant seal (Mirounga
      leonina).
AB  - A previously unknown Gram-positive, catalase-positive, facultatively anaerobic,
      non-spore-forming, coccus-shaped bacterium (A/G14/99/10(T)), originating from the
      mouth of a female southern elephant seal, was subjected to a taxonomic analysis.
      Comparative 16S rRNA gene-sequencing showed that the organism formed a hitherto
      unknown subline within the catalase-positive, low-G+C, Gram-positive cocci,
      exhibiting a specific association with species of the genus Jeotgalicoccus.
      Sequence divergence values of approximately 7 %, together with phenotypic
      differences, showed the unknown bacterium to be distinct from the two described
      species of this genus, Jeotgalicoccus halotolerans and Jeotgalicoccus
      psychrophilus. Based on phenotypic and phylogenetic considerations, it is
      proposed that strain A/G14/99/10(T)=CCUG 42722(T)=CIP 107946(T) from the mouth of
      a seal be classified as the type strain of a novel species of the genus
      Jeotgalicoccus, Jeotgalicoccus pinnipedialis sp. nov.

PMID- 15143017
TI  - Anaerobranca californiensis sp. nov., an anaerobic, alkalithermophilic,
      fermentative bacterium isolated from a hot spring on Mono Lake.
AB  - A novel, obligately anaerobic, alkalithermophilic, chemo-organotrophic bacterium
      was isolated from the sediment of an alkaline hot spring located on Paoha Island
      in Mono Lake, California, USA. This rod-shaped bacterium was motile via
      peritrichous flagella. Isolated strains grew optimally in 5-25 g NaCl l(-1), at
      pH 9.0-9.5 and at a temperature of 58 degrees C and were fermentative and mainly
      proteolytic, utilizing peptone, Casamino acids and yeast extract. Optimal growth
      was seen in the presence of elemental sulfur, polysulfide or thiosulfate with
      concomitant reduction to hydrogen sulfide. Sulfite was also formed in an equal
      ratio to sulfide during reduction of thiosulfate. The novel isolate could also
      reduce Fe(III) and Se(IV) in the presence of organic matter. On the basis of
      physiological properties, 16S rRNA gene sequence and DNA-DNA hybridization data,
      strain PAOHA-1(T) (=DSM 14826(T)=UNIQEM 227(T)) belongs to the genus Anaerobranca
      and represents a novel species, Anaerobranca californiensis sp. nov.

PMID- 15143019
TI  - Pseudonocardia benzenivorans sp. nov.
AB  - A Gram-positive, rod-shaped, non-spore-forming bacterium (B5(T)) was isolated
      from an enrichment culture that contained 1,2,3,5-tetrachlorobenzene as the sole
      source of carbon. On the basis of 16S rRNA gene sequence similarity studies,
      strain B5(T) was shown to belong to the family Pseudonocardiaceae and was related
      most closely to Pseudonocardia sulfidoxydans (98.8 %) and Pseudonocardia
      hydrocarbonoxydans (98.3 %). 16S rRNA gene sequence similarity to other
      Pseudonocardia species was <97 %. Chemotaxonomic data [major menaquinone, MK
      8(H(4)); major polar lipids, diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylinositol; major fatty acids, C(16 : 0), iso-C(16 : 0) and iso-C(15 :
      0)] supported the affiliation of strain B5(T) to the genus Pseudonocardia. The
      results of DNA-DNA hybridizations and physiological and biochemical tests allowed
      genotypic and phenotypic differentiation of strain B5(T) from P. sulfidoxydans
      and P. hydrocarbonoxydans. Strain B5(T) therefore represents a novel species of
      the genus Pseudonocardia, for which the name Pseudonocardia benzenivorans sp.
      nov. is proposed, with the type strain B5(T) (=DSM 44703(T)=CIP 107928(T)).

PMID- 15143020
TI  - Phylogenetic analysis of gastric and enterohepatic Helicobacter species based on
      partial HSP60 gene sequences.
AB  - Analysis of 16S rRNA gene sequences has been the method generally used to study
      the evolution and phylogeny of bacteria. Phylogenetic analysis of the 16S rRNA
      gene has shown the position of the genus Helicobacter in the epsilon-subclass of
      the Proteobacteria. Because 16S rRNA-based phylogeny does not always correspond
      to the results of polyphasic taxonomy, and the related species cannot always be
      separated, new phylogenetic markers for Helicobacter species are needed. In this
      study, conserved partial (600 bp) 60 kDa heat-shock protein (HSP60) sequences
      were used to study the phylogeny of 37 strains of gastric and enterohepatic
      Helicobacter species, including type strains of 15 Helicobacter species with
      validly published names, reference strains of flexispira taxa and Helicobacter
      felis, Helicobacter bizzozeronii and Helicobacter salomonis and canine flexispira
      strains. The partial HSP60 gene sequence proved to be a useful phylogenetic
      marker for the genus Helicobacter, providing a means of differentiating all 15
      Helicobacter species analysed. In the resulting phylogenetic tree, gastric
      Helicobacter species and enterohepatic species with flexispira morphology formed
      tight, separate clusters. In general, HSP60 sequence similarities between
      Helicobacter species were significantly lower than the corresponding 16S rRNA
      gene sequence similarities, indicating a better resolution for species
      identification. In addition, a specific PCR method for identifying H. salomonis
      was developed based on the partial HSP60 sequence.

PMID- 15143021
TI  - Methanobacterium aarhusense sp. nov., a novel methanogen isolated from a marine
      sediment (Aarhus Bay, Denmark).
AB  - Strain H2-LR(T), a 5-18 micro m long and 0.7 micro m wide filamentous,
      mesophilic, moderately halophilic, non-motile hydrogenotrophic methanogen, was
      isolated from marine sediment of Aarhus Bay, Denmark, 1.7 m below the sediment
      surface. On the basis of 16S rRNA gene comparison with sequences of known
      methanogens, strain H2-LR(T) could be affiliated to the genus Methanobacterium.
      The strain forms a distinct line of descent within this genus, with
      Methanobacterium oryzae (95.9 % sequence identity) and Methanobacterium bryantii
      (95.7 % sequence identity) as its closest relatives. The 16S rRNA-based
      affiliation was supported by comparison of the mcrA gene, which encodes the alpha
      subunit of methyl-coenzyme M reductase. Strain H2-LR(T) grew only on H(2)/CO(2).
      The DNA G+C content is 34.9 mol%. Optimum growth temperature was 45 degrees C.
      The strain grew equally well at pH 7.5 and 8. No growth or methane production was
      observed below pH 5 or above pH 9. Strain H2-LR(T) grew well within an NaCl
      concentration range of 100 and 900 mM. No growth or methane production was
      observed at 1 M NaCl. At 50 mM NaCl, growth and methane production were reduced.
      Based on 16S rRNA gene sequence analysis, the isolate is proposed to represent a
      novel taxon within the genus Methanobacterium, namely Methanobacterium aarhusense
      sp. nov. The type strain is H2-LR(T) (=DSM 15219(T)=ATCC BAA-828(T)).

PMID- 15143022
TI  - Repeat-type distribution in trnL intron does not correspond with species
      phylogeny: comparison of the genetic markers 16S rRNA and trnL intron in
      heterocystous cyanobacteria.
AB  - tRNA(Leu) UAA (trnL) intron sequences are used as genetic markers for
      differentiating cyanobacteria and for constructing phylogenies, since the introns
      are thought to be more variable among close relatives than is the 16S rRNA gene,
      the conventional phylogenetic marker. The evolution of trnL intron sequences and
      their utility as a phylogenetic marker were analysed among heterocystous
      cyanobacteria with maximum-parsimony, maximum-likelihood and Bayesian inference
      by comparing their evolutionary information to that of the 16S rRNA gene. Trees
      inferred from the 16S rRNA gene and the distribution of two repeat classes in the
      P6b stem-loop of the trnL intron were in clear conflict. The results show that,
      while similar heptanucleotide repeat classes I and II in the P6b stem-loop of the
      trnL intron could be found among distant relatives, some close relatives
      harboured different repeat classes with a high sequence difference. Moreover,
      heptanucleotide repeat class II and other sequences from the P6b stem-loop of the
      trnL intron interrupted several other intergenic regions in the genomes of
      heterocystous cyanobacteria. Cluster analyses based on conserved intron sequences
      without loops P6b, P9 and parts of P5 corresponded in most clades to the 16S rRNA
      gene phylogeny, although the relationships were not resolved well, according to
      low bootstrap support. Thus, the hypervariable loop sequences of the trnL intron,
      especially the P6b stem-loop, cannot be used for phylogenetic analysis and
      conclusions cannot be drawn about species relationships on the basis of these
      elements. Evolutionary scenarios are discussed considering the origin of the
      repeats.

PMID- 15143023
TI  - Arthrobacter nitroguajacolicus sp. nov., a novel 4-nitroguaiacol-degrading
      actinobacterium.
AB  - Three bacterial isolates from soil, capable of degradation or transformation of
      nitroaromatic compounds and displaying a rod-coccus growth cycle, were studied by
      a polyphasic approach. On the basis of 16S rRNA sequence analysis and of
      chemotaxonomic characteristics, such as type A3alpha peptidoglycan with an
      interpeptide bridge Ala-Thr-Ala, the major menaquinone MK-9(H(2)) and fatty acid
      composition, the isolates were assigned to the genus Arthrobacter. DNA-DNA
      hybridization, riboprinting and phenotypic studies revealed that the three
      strains constitute a single species, distinct from phylogenetically neighbouring
      Arthrobacter aurescens and Arthrobacter ilicis. A novel species, Arthrobacter
      nitroguajacolicus sp. nov., with the type strain G2-1(T) (=CCM 4924(T)=DSM
      15232(T)) is proposed.

PMID- 15143024
TI  - Corynebacterium halotolerans sp. nov., isolated from saline soil in the west of
      China.
AB  - A halotolerant, non-spore-forming actinobacterium was isolated from a soil sample
      from the west of China. The strain, designated YIM 70093(T) (=CCTCC AA
      001024(T)=DSM 44683(T)), comprised Gram-positive, non-motile, diphtheroid and
      irregular rods. It grew in 0-25 % KCl (KCl could be substituted by NaCl or
      MgCl(2).6H(2)O), with optimum growth at 10 % KCl, and its optimal pH and
      cultivation temperature were 7.2 and 28 degrees C, respectively. On the basis of
      its morphological, physiological and phylogenetic characteristics, strain YIM
      70093(T) should be classified in the genus CORYNEBACTERIUM: However, it is
      sufficiently different from hitherto described Corynebacterium species to be
      considered as a novel species, for which the name Corynebacterium halotolerans
      sp. nov. is proposed.

PMID- 15143025
TI  - Gulosibacter molinativorax gen. nov., sp. nov., a molinate-degrading bacterium,
      and classification of 'Brevibacterium helvolum' DSM 20419 as Pseudoclavibacter
      helvolus gen. nov., sp. nov.
AB  - A Gram-positive, molinate-degrading bacterium, strain ON4(T) (=DSM 13485(T)=LMG
      21909(T)), was isolated from a mixed bacterial culture able to mineralize the
      herbicide molinate. The strain was strictly aerobic, oxidase- and catalase
      positive and non-acid-fast, with a growth temperature of 10-41 degrees C. It
      contained the major menaquinone MK-9 and a cell-wall peptidoglycan based on D
      ornithine. 16S rDNA sequence analysis revealed that the strain formed a distinct
      line of descent in the family Microbacteriaceae, showing the highest 16S rDNA
      similarity ( approximately 95 %) to members of the genus Curtobacterium and
      'Brevibacterium helvolum' DSM 20419 (=ATCC 13715). The latter was reported to
      have the cell-wall peptidoglycan type B2gamma and the major menaquinone MK-9,
      which are typical of Clavibacter, but it is clearly separated from this genus at
      the phylogenetic level. Based on low values of 16S rDNA sequence similarity to
      previously described genera and their distinctive phenotypic characteristics, it
      is proposed that strains ON4(T) and 'B. helvolum' DSM 20419 be classified as two
      novel genera and species, with the respective names Gulosibacter molinativorax
      gen. nov., sp. nov. and Pseudoclavibater helvolus gen. nov., sp. nov.

PMID- 15143026
TI  - Evaluation of the phylogenetic position of the planctomycete 'Rhodopirellula
      baltica' SH 1 by means of concatenated ribosomal protein sequences, DNA-directed
      RNA polymerase subunit sequences and whole genome trees.
AB  - In recent years, the planctomycetes have been recognized as a phylum of
      environmentally important bacteria with habitats ranging from soil and freshwater
      to marine ecosystems. The planctomycetes form an independent phylum within the
      bacterial domain, whose exact phylogenetic position remains controversial. With
      the completion of sequencing of the genome of 'Rhodopirellula baltica' SH 1, it
      is now possible to re-evaluate the phylogeny of the planctomycetes based on
      multiple genes and genome trees in addition to single genes like the 16S rRNA or
      the elongation factor Tu. Here, evidence is presented based on the concatenated
      amino acid sequences of ribosomal proteins and DNA-directed RNA polymerase
      subunits from 'Rhodopirellula baltica' SH 1 and more than 90 other publicly
      available genomes that support a relationship of the Planctomycetes and the
      Chlamydiae. Affiliation of 'Rhodopirellula baltica' SH 1 and the Chlamydiae was
      reasonably stable regarding site selection since, during stepwise filtering of
      less-conserved sites from the alignments, it was only broken when rigorous
      filtering was applied. In a few cases, 'Rhodopirellula baltica' SH 1 shifted to a
      deep branching position adjacent to the Thermotoga/Aquifex clade. These findings
      are in agreement with recent publications, but the deep branching position was
      dependent on site selection and treeing algorithm and thus not stable. A genome
      tree calculated from normalized BLASTP scores did not confirm a close
      relationship of 'Rhodopirellula baltica' SH 1 and the Chlamydiae, but also
      indicated that the Planctomycetes do not emerge at the very root of the Bacteria.
      Therefore, these analyses rather contradict a deep branching position of the
      Planctomycetes within the bacterial domain and reaffirm their earlier proposed
      relatedness to the Chlamydiae.

PMID- 15143027
TI  - Bacillus hwajinpoensis sp. nov. and an unnamed Bacillus genomospecies, novel
      members of Bacillus rRNA group 6 isolated from sea water of the East Sea and the
      Yellow Sea in Korea.
AB  - Two Gram-positive or -variable, endospore-forming, slightly halophilic strains
      (SW-72(T) and SW-93) were isolated from sea water of the East Sea and the Yellow
      Sea in Korea, respectively, and subjected to polyphasic taxonomic study. Both
      strains had cell-wall peptidoglycan that was based on meso-diaminopimelic acid
      and MK-7 as the predominant menaquinone. The two strains contained large amounts
      of saturated and branched fatty acids, with anteiso-C(15 : 0) as the major fatty
      acid. The DNA G+C contents of strains SW-72(T) and SW-93 were 40.9 and 41.0 mol%,
      respectively. Phylogenetic analysis based on 16S rDNA sequences showed that
      strains SW-72(T) and SW-93 fall within the radiation of the cluster that
      comprises members of the genus Bacillus, particularly Bacillus rRNA group 6.
      There were five nucleotide differences between the 16S rDNA sequences of strains
      SW-72(T) and SW-93. The mean level of DNA-DNA relatedness between strains SW
      72(T) and SW-93 was 21.5 %. Strains SW-72(T) and SW-93 showed 93.1-95.2 % 16S
      rDNA sequence similarity to the type strains of Bacillus species that are
      assigned to rRNA group 6. Strains SW-72(T) and SW-93 could not be differentiated
      clearly by using their phenotypic properties. On the basis of phenotypic
      properties, phylogeny and genomic data, it is proposed that strain SW-72(T)
      (=KCCM 41641(T)=JCM 11807(T)) should be placed in the genus Bacillus as the type
      strain of a novel species, Bacillus hwajinpoensis sp. nov., and that strain SW-93
      (=KCCM 41640=JCM 11806) should be placed in the genus Bacillus as an unnamed
      Bacillus genomospecies.

PMID- 15143028
TI  - Reclassification of Lactobacillus cellobiosus Rogosa et al. 1953 as a later
      synonym of Lactobacillus fermentum Beijerinck 1901.
AB  - The name Lactobacillus cellobiosus is validly published, but the species is often
      neglected in taxonomic studies, due to its high similarity to Lactobacillus
      fermentum. In the present paper, literature data concerning the two species were
      reviewed. Phylogenetic placement of L. cellobiosus was obtained based on 16S rDNA
      sequences, and genetic similarity was further investigated by comparing partial
      recA gene sequences for the type strains of L. cellobiosus and L. fermentum.
      Based on the high identity values for 16S rDNA (99 %) and recA gene (98 %)
      sequences, the results of DNA-DNA hybridization assays and phenotypic traits
      available from the literature, it is proposed that L. cellobiosus be reclassified
      and, as a rule of priority, renamed as L. fermentum, the first described species.

PMID- 15143029
TI  - Reclassification of Bisgaard taxon 33, with proposal of Volucribacter
      psittacicida gen. nov., sp. nov. and Volucribacter amazonae sp. nov. as new
      members of the Pasteurellaceae.
AB  - A total of 25 strains isolated from parrots, budgerigars, parakeets
      (Psittaciformes) and a chicken, mostly associated with respiratory disease or
      septicaemia, were classified as a new genus, Volucribacter gen. nov., within the
      family Pasteurellaceae, on the basis on unique phenotypic characteristics and
      clear monophyly as determined by 16S rRNA gene sequence comparison. Comparison of
      16S rRNA gene sequences from six strains showed at least 98.8 % similarity and
      the closest similarity outside the genus was found to Bisgaard taxon 34 and to
      Pasteurella avium, at 94.6 and 94.5 %, respectively. Phenotypes that separate the
      new genus from other genera of the Pasteurellaceae included at least two
      characters. The genus includes two species, Volucribacter psittacicida sp. nov.
      and Volucribacter amazonae sp. nov., corresponding to the two biovars previously
      outlined, underlining that most isolates have been obtained from psittacine
      birds. The two species can be separated by fermentation of meso-inositol, (-)-L
      fucose, maltose and dextrin and a positive ONPG test. The type strains for
      Volucribacter psittacicida and Volucribacter amazonae are respectively Gerl.
      236/81(T) (=CCUG 47536(T)=DSM 15534(T)) and 146/S8/89(T) (=CCUG 47537(T)=DSM
      15535(T)).

PMID- 15143030
TI  - Sphingomonas yabuuchiae sp. nov. and Brevundimonas nasdae sp. nov., isolated from
      the Russian space laboratory Mir.
AB  - On the basis of phenotypic and genotypic characteristics and 16S rRNA gene
      sequence analysis, novel species belonging to the genera Sphingomonas and
      Brevundimonas were identified from samples taken from the Russian space
      laboratory Mir. Strain A1-18(T) was isolated from the air. 16S rDNA sequence
      analysis showed that strain A1-18(T) formed a coherent cluster with Sphingomonas
      sanguinis, Sphingomonas parapaucimobilis, Sphingomonas paucimobilis and
      Sphingomonas roseiflava with sequence similarity of 97.5-98.6 %. Similar to other
      Sphingomonas species, the G+C content was 66.1 mol%, but DNA-DNA hybridization
      rates at optimal temperatures among these related species were only 24.7-51.7 %.
      Strain A1-18(T) can be differentiated biochemically from related species. Strain
      W1-2B(T) was isolated from condensation water. It forms a distinct lineage within
      the genus Brevundimonas, forming a coherent cluster with Brevundimonas
      vesicularis, Brevundimonas aurantiaca and Brevundimonas intermedia. 16S rDNA
      sequence similarities were 98.6-99.5 % and the G+C content was 66.5 mol%, similar
      to other Brevundimonas species, but DNA-DNA relatedness was only 50.2-54.8 %.
      Strain W1-2B(T) also showed some differential biochemical properties from its
      related species. A series of polyphasic taxonomic studies led to the proposal of
      two novel species, Sphingomonas yabuuchiae sp. nov. (type strain A1-18(T)=GTC
      868(T)=JCM 11416(T)=DSM 14562(T)) and Brevundimonas nasdae sp. nov. (type strain
      W1-2B(T)=GTC 1043(T)=JCM 11415(T)=DSM 14572(T)).

PMID- 15143032
TI  - Nesterenkonia halotolerans sp. nov. and Nesterenkonia xinjiangensis sp. nov.,
      actinobacteria from saline soils in the west of China.
AB  - The taxonomic position of two Gram-positive strains, YIM 70084(T) and YIM
      70097(T), isolated from hypersaline soils was determined by a polyphasic
      approach. Cells of strain YIM 70084(T) are motile cocci, whereas those of strain
      YIM 70097(T) are non-motile rods. The G+C contents of their DNA are 64.4 and 66.7
      mol%. Both strains had chemotaxonomic markers typical of the genus Nesterenkonia
      and formed a coherent cluster with Nesterenkonia species in a phylogenetic
      inference based on 16S rDNA sequence analysis, exhibiting less than 97 %
      similarity to each other and to the other two type strains of the genus.
      Phylogenetic distinction and differences in the peptidoglycan type, composition
      of cell-wall sugars, phospholipid patterns, the major menaquinones and other
      phenotypic characteristics indicate that the strains under study represent two
      novel species, Nesterenkonia halotolerans sp. nov. (type strain YIM
      70084(T)=CCTCC AA 001022(T)=DSM 15474(T)) and Nesterenkonia xinjiangensis sp.
      nov. (type strain YIM 70097(T)=CCTCC AA 001025(T)=DSM 15475(T)).

PMID- 15143031
TI  - Rothia aeria sp. nov., Rhodococcus baikonurensis sp. nov. and Arthrobacter
      russicus sp. nov., isolated from air in the Russian space laboratory Mir.
AB  - Four Gram-positive bacteria, strains A1-17B(T), A1-22(T), A1-3(T) and A1-8,
      isolated from the air in the Russian space laboratory Mir, were subjected to a
      polyphasic taxonomic study. Phylogenetic analysis of the bacteria based on their
      16S rDNA sequence showed that they belong to the genera Rothia (A1-17B(T)),
      Rhodococcus (A1-22(T)) and Arthrobacter (A1-3(T) and A1-8). Morphological,
      physiological, chemotaxonomic and genomic characteristics supported the
      assignments of these strains to these genera, but they could not be classified as
      any existing species within each respective genus. 16S rDNA similarity values
      between strain A1-17B(T) and its neighbours, Rothia dentocariosa genomovar II,
      Rothia dentocariosa, Rothia mucilaginosa and Rothia nasimurium, were respectively
      99.8, 98.0, 96.4 and 95.4 %. Polyphasic taxonomic evidence indicated that strain
      A1-17B(T) should be categorized together with the unofficially named Rothia
      dentocariosa genomovar II, but clearly differentiated them from the established
      species of the genus ROTHIA: Strain A1-22(T) formed a coherent cluster with
      Rhodococcus erythropolis, Rhodococcus globerulus, Rhodococcus marinonascens and
      Rhodococcus percolatus in 16S rDNA sequence analysis, but DNA-DNA relatedness
      values were only 45.5, 35.3, 18.9 and 21.9 %. Strains A1-3(T) and A1-8 shared
      99.9 % 16S rDNA sequence similarity, and strain A1-3(T) showed the highest level
      of 16S rDNA similarity, 96.6 %, to Arthrobacter polychromogenes. Contrasting
      biochemical characteristics were also identified. Finally, as a result of the
      polyphasic taxonomic study, three of the strains are proposed as type strains of
      novel species: Rothia aeria sp. nov. (A1-17B(T)=GTC 867(T)=JCM 11412(T)=DSM
      14556(T)), Rhodococcus baikonurensis sp. nov. (A1-22(T)=GTC 1041(T)=JCM
      11411(T)=DSM 44587(T)) and Arthrobacter russicus sp. nov. (A1-3(T)=GTC 863(T)=JCM
      11414(T)=DSM 14555(T)).

PMID- 15143033
TI  - Vibrio gallicus sp. nov., isolated from the gut of the French abalone Haliotis
      tuberculata.
AB  - Five alginolytic, facultatively anaerobic, non-motile bacteria were isolated from
      the gut of the abalone Haliotis tuberculata. Phylogenetic analyses based on 16S
      rDNA data indicated that these strains are related to Vibrio wodanis, Vibrio
      salmonicida, Vibrio logei and Vibrio fischeri (but with <97 % 16S rRNA gene
      sequence similarity). DNA-DNA hybridization and fluorescence amplified fragment
      length polymorphism fingerprinting demonstrated that the five strains constituted
      a single species that was different from all currently known vibrios. The name
      Vibrio gallicus sp. nov. (type strain, CIP 107863(T)=LMG 21878(T)=HT2-1(T); DNA
      G+C content, 43.6-44.3 mol%) is proposed for this novel taxon. Several phenotypic
      features were disclosed that discriminated V. gallicus from other Vibrio species:
      V. gallicus can be differentiated from Vibrio halioticoli on the basis of four
      traits (beta-galactosidase test and assimilation of three carbon compounds) and
      from Vibrio superstes by 16 traits.

PMID- 15143034
TI  - Pseudomonas lutea sp. nov., a novel phosphate-solubilizing bacterium isolated
      from the rhizosphere of grasses.
AB  - A phosphate-solubilizing bacterial strain designated OK2(T) was isolated from
      rhizospheric soil of grasses growing spontaneously in a soil from Spain. Cells of
      the strain were Gram-negative, strictly aerobic, rod-shaped and motile.
      Phylogenetic analysis of the 16S rRNA gene indicated that this bacterium belongs
      to the gamma-subclass of Proteobacteria within the genus Pseudomonas and that the
      closest related species is Pseudomonas graminis. The strain produced catalase but
      not oxidase. Cellulose, casein, starch, gelatin and urea were not hydrolysed.
      Aesculin was hydrolysed. Growth was observed with many carbohydrates as carbon
      sources. The main non-polar fatty acids detected were hexadecenoic acid (16 : 1),
      hexadecanoic acid (16 : 0) and octadecenoic acid (18 : 1). The hydroxy fatty
      acids detected were 3-hydroxydecanoic acid (3-OH 10 : 0), 3-hydroxydodecanoic
      acid (3-OH 12 : 0) and 2-hydroxydodecanoic acid (2-OH 12 : 0). The G+C DNA
      content determined was 59.3 mol%. DNA-DNA hybridization showed 48.7 % relatedness
      between strain OK2(T) and P. graminis DSM 11363(T) and 26.2 % with respect to
      Pseudomonas rhizosphaerae LMG 21640(T). Therefore, these results indicate that
      strain OK2(T) (=LMG 21974(T)=CECT 5822(T)) belongs to a novel species of the
      genus Pseudomonas, and the name Pseudomonas lutea sp. nov. is proposed.

PMID- 15143035
TI  - Herbaspirillum chlorophenolicum sp. nov., a 4-chlorophenol-degrading bacterium.
AB  - A 4-chlorophenol-degrading bacterial strain, formerly designated as a strain of
      Comamonas testosteroni, was reclassified as a member of the genus Herbaspirillum
      based on its phenotypic and chemotaxonomic characteristics, as well as
      phylogenetic analysis using 16S rDNA sequences. Phylogenetic inference based on
      16S rDNA sequences showed that strain CPW301(T) clusters in a phylogenetic branch
      that contains Herbaspirillum species. 16S rDNA sequence similarity of strain
      CPW301(T) to species of the genus Herbaspirillum with validly published names is
      in the range 98.7-98.9 %. Despite the considerably high 16S rDNA sequence
      similarity, strain CPW301(T) could be distinguished clearly from type strains of
      Herbaspirillum species with validly published names by DNA-DNA relatedness
      values, which were <15.7 %. The genomic DNA G+C content of strain CPW301(T) is
      61.3 mol%. The predominant ubiquinone is Q-8 and the major cellular fatty acids
      are C(16 : 0) and cyclo-C(17 : 0). The strain does not fix nitrogen and is not
      plant-associated. It is an aerobic rod with one unipolar flagellum. On the basis
      of these characteristics, a novel Herbaspirillum species, Herbaspirillum
      chlorophenolicum sp. nov., is proposed. The type strain of the novel species is
      strain CPW301(T) (=KCTC 12096(T)=IAM 15024(T)).

PMID- 15143036
TI  - Collimonas fungivorans gen. nov., sp. nov., a chitinolytic soil bacterium with
      the ability to grow on living fungal hyphae.
AB  - A polyphasic approach was used to describe the phylogenetic position of 22
      chitinolytic bacterial isolates that were able to grow at the expense of intact,
      living hyphae of several soil fungi. These isolates, which were found in slightly
      acidic dune soils in the Netherlands, were strictly aerobic, Gram-negative rods.
      Cells grown in liquid cultures were flagellated and possessed pili. A wide range
      of sugars, alcohols, organic acids and amino acids could be metabolized, whereas
      several di- and trisaccharides could not be used as substrates. The major
      cellular fatty acids were C(16 : 0), C(16 : 1)omega7c and C(18 : 1)omega7c. DNA
      G+C contents were 57-62 mol%. Analysis of nearly full-length 16S rDNA sequences
      showed that the isolates were related closely to each other (>98.6 % sequence
      similarity) and could be assigned to the beta-Proteobacteria, family
      'Oxalobacteraceae', order 'Burkholderiales'. The most closely related species
      belonged to the genera Herbaspirillum and Janthinobacterium, exhibiting 95.9-96.7
      % (Herbaspirillum species) and 94.3-95.6 % (Janthinobacterium species) 16S rDNA
      sequence similarity to the isolates. Several physiological and biochemical
      properties indicated that the isolates could be distinguished clearly from both
      of these genera. Therefore, it is proposed that the isolates described in this
      study are representatives of a novel genus, Collimonas gen. nov. Genomic
      fingerprinting (BOX-PCR), detailed analysis of 16S rDNA patterns and
      physiological characterization (Biolog) of the isolates revealed the existence of
      four subclusters. The name Collimonas fungivorans gen. nov., sp. nov. has been
      given to one subcluster (four isolates) that appears to be in the centre of the
      novel genus; isolates in the other subclusters have been tentatively named
      Collimonas sp. The type strain of Collimonas fungivorans gen. nov., sp. nov. is
      Ter6(T) (=NCCB 100033(T)=LMG 21973(T)).

PMID- 15143037
TI  - Emendation of the genus Acidomonas Urakami, Tamaoka, Suzuki and Komagata 1989.
AB  - The genus Acidomonas and the species Acidomonas methanolica were recharacterized
      by using the type strain (NRIC 0498(T)), three reference strains and 10 methanol
      utilizing bacteria that were isolated from activated sludge from three different
      sewage-treatment plants in Tokyo. Based on 16S rDNA sequences, all strains formed
      a single cluster within the Acetobacteraceae that was clearly different from the
      genera Acetobacter, Gluconobacter, Gluconacetobacter, Asaia and KOZAKIA: The 14
      strains were identified as a single species, Acidomonas methanolica, by DNA-DNA
      similarities, showed DNA G+C contents that ranged from 62 to 63 mol% and had Q-10
      as the major quinone, accounting for >87 % of total ubiquinones. Cells of
      Acidomonas methanolica had a single polar flagellum (or occasionally polar tuft
      flagella); this differs from a previous study that described peritrichous
      flagella. Oxidation of acetate was positive for all strains, but oxidation of
      lactate was weakly positive and varied with strains. Dihydroxyacetone was not
      produced from glycerol. Pantothenic acid was an essential requirement for growth.
      The strains tested grew at mostly the same extent at pH 3.0-8.0. Therefore,
      Acidomonas methanolica should be regarded as acidotolerant, not acidophilic. The
      descriptions of the genus Acidomonas and the species Acidomonas methanolica
      Urakami, Tamaoka, Suzuki and Komagata 1989 are emended with newly obtained data.

PMID- 15143038
TI  - Phylogeny of Firmicutes with special reference to Mycoplasma (Mollicutes) as
      inferred from phosphoglycerate kinase amino acid sequence data.
AB  - The phylogenetic position of the Mollicutes has been re-examined by using
      phosphoglycerate kinase (Pgk) amino acid sequences. Hitherto unpublished
      sequences from Mycoplasma mycoides subsp. mycoides, Mycoplasma hyopneumoniae and
      Spiroplasma citri were included in the analysis. Phylogenetic trees based on Pgk
      data indicated a monophyletic origin for the Mollicutes within the Firmicutes,
      whereas Bacilli (Firmicutes) and Clostridia (Firmicutes) appeared to be
      paraphyletic. With two exceptions, i.e. Thermotoga (Thermotogae) and
      Fusobacterium (Fusobacteria), which clustered within the Firmicutes, comparative
      analyses show that at a low taxonomic level, the resolved phylogenetic
      relationships that were inferred from both the Pgk protein and 16S rRNA gene
      sequence data are congruent.

PMID- 15143039
TI  - Prevotella shahii sp. nov. and Prevotella salivae sp. nov., isolated from the
      human oral cavity.
AB  - Two bacterial strains, EHS11(T) and EPSA11(T), which were isolated from the human
      oral cavity, were characterized in terms of phenotypic and biochemical
      characteristics, cellular fatty acid profiles and phylogenetic position based on
      16S rRNA gene sequence analysis. 16S rRNA gene sequence analysis showed that each
      of the isolates belonged to a novel species of the genus Prevotella. Strain
      EHS11(T) was related to Prevotella loescheii (about 95 % similarity), whereas
      strain EPSA11(T) was related to Prevotella oris (about 94 % similarity). Both
      strains were obligately anaerobic, non-pigmented, non-spore-forming, non-motile,
      Gram-negative rods. The cellular fatty acid composition of strain EPSA11(T) was
      very similar to that of P. oris JCM 8540(T). On the other hand, the cellular
      fatty acid composition of strain EHS11(T) was significantly different from those
      of other Prevotella species. The predominant fatty acids in strain EHS11(T) are
      C(18 : 1)omega9c, C(16 : 0) and C(16 : 0) 3-OH, whereas other Prevotella species,
      except for P. loescheii JCM 8530(T), possess anteiso-C(15 : 0), iso-C(17 : 0) 3
      OH and C(18 : 1)omega9c. The predominant fatty acids in P. loescheii JCM 8530(T)
      are anteiso-C(15 : 0), C(16 : 0) and C(18 : 1)omega9c. DNA-DNA hybridization
      experiments revealed a genomic distinction of strains EHS11(T) and EPSA11(T) from
      P. loescheii JCM 8530(T) and P. oris JCM 8540(T). On the basis of these data, two
      novel Prevotella species are proposed: Prevotella shahii sp. nov. and Prevotella
      salivae sp. nov. The type strains of P. shahii and P. salivae are EHS11(T) (=JCM
      12083(T)=DSM 15611(T)) and EPSA11(T) (=JCM 12084(T)=DSM 15606(T)), respectively.

PMID- 15143040
TI  - Paenibacillus lactis sp. nov., isolated from raw and heat-treated milk.
AB  - Endospore-forming bacteria were recovered from individual packages from different
      processing lines in a dairy plant during a tenacious periodical contamination of
      their UHT-milk production. Two colony types were seen, one of which was
      identified as Bacillus sporothermodurans. Analysis of the 16S rRNA gene of the
      second colony type placed these isolates within the genus Paenibacillus, with
      Paenibacillus lautus as the closest known relative. Moreover, over 99 %
      similarity was observed to the 16S rDNA sequence of MB 2035, a strain isolated
      previously from raw milk during a survey at dairy farms for very heat-resistant
      spore-forming bacteria. Nine other potentially closely related strains among the
      dairy farm isolates were found using rep-PCR typing. The taxonomic positions of
      these 19 isolates were further investigated using 16S rRNA gene sequencing and
      DNA-DNA hybridizations of representative strains. All 19 isolates shared a high
      degree of phenotypic similarity and were easily distinguished from closely
      related members of the genus. Anteiso-C(15 : 0), C(16 : 0) and iso-C(15 : 0) were
      among the major fatty acids and the genomic DNA G+C content was 51.6-51.7 mol%.
      Therefore, based on their phenotypic, phylogenetic and genomic distinctiveness,
      these 19 strains, isolated from both raw and heat-treated milk, are placed in the
      genus Paenibacillus as Paenibacillus lactis sp. nov. The type strain is MB
      1871(T) (=LMG 21940(T)=DSM 15596(T)).

PMID- 15143041
TI  - The genus Spiroplasma and its non-helical descendants: phylogenetic
      classification, correlation with phenotype and roots of the Mycoplasma mycoides
      clade.
AB  - The genus Spiroplasma (helical mollicutes: Bacteria: Firmicutes: Mollicutes:
      Entomoplasmatales: Spiroplasmataceae) is associated primarily with insects. The
      Mycoplasma mycoides cluster (sensu Weisburg et al. 1989 and Johansson and
      Pettersson 2002) is a group of mollicutes that includes the type species -
      Mycoplasma mycoides - of Mycoplasmatales, Mycoplasmataceae and Mycoplasma. This
      cluster, associated solely with ruminants, contains five other species and
      subspecies. Earlier phylogenetic reconstructions based on partial 16S rDNA
      sequences and a limited sample of Spiroplasma and Mycoplasma sequences suggested
      that the genus Mycoplasma was polyphyletic, as the M. mycoides cluster and the
      grouping that consisted of the hominis and pneumoniae groups of Mycoplasma
      species were widely separated phylogenetically and the M. mycoides cluster was
      allied with Spiroplasma. It is shown here that the M. mycoides cluster arose from
      Spiroplasma through an intermediate group of non-helical spiroplasmal descendants
      - the Entomoplasmataceae. As this conclusion has profound implications in the
      taxonomy of Mollicutes, a detailed phylogenetic study of Spiroplasma and its non
      helical descendants was undertaken. These analyses, done with maximum-parsimony,
      provide cladistic status; a new nomenclature is introduced here, based on 'bottom
      up' rather than 'top-down' clade classification. The order Entomoplasmatales
      consists of four major clades: (i) the Mycoides-Entomoplasmataceae clade, which
      contains M. mycoides and its allies and Entomoplasma and Mesoplasma species and
      is a sister lineage to (ii) the Apis clade of Spiroplasma. Spiroplasma and the
      Entomoplasmataceae are paraphyletic, but this status does not diminish their
      phylogenetic usefulness. Five species that were previously unclassified
      phylogenetically are basal to the Apis clade sensu strictu and to the Mycoides
      clade. One of these species, Spiroplasma sp. TIUS-1, has very poor helicity and a
      very small genome (840 kbp); this putative species can be envisioned as a
      'missing link' in the evolution of the Mycoides-Entomoplasmataceae clade. The
      other two Spiroplasma clades are: (iii) the Citri-Chrysopicola-Mirum clade
      (serogroups I, II, V and VIII) and (iv) the ixodetis clade (serogroup VI). As
      Mesoplasma lactucae represents a basal divergence within the Mycoides
      Entomoplasmataceae clade, and as Entomoplasma freundtii is basal to the Mycoides
      clade, M. mycoides and its allies must have arisen from an ancestor in the
      Entomoplasmataceae. The paraphyletic grouping that consists of the Hominis and
      Pneumoniae groups (sensu Johansson & Pettersson 2002) of Mycoplasma species
      contains the ancestral roots of Ureaplasma spp. and haemoplasmas. This clade is a
      sister lineage to the Entomoplasmatales clade. Serological classifications of
      spiroplasma are very highly supported by the trees presented. Genome size and G+C
      content of micro-organismal DNA were moderately conserved, but there have been
      frequent and polyphyletically distributed genome reductions. Sterol requirements
      were polyphyletic, as was the ability to grow in the presence of polyoxyethylene
      sorbitan-supplemented, but not serum-supplemented, media. As this character is
      not phylogenetically distributed, Mesoplasma and Entomoplasma should be combined
      into a single genus. The phylogenetic trees presented here confirm previous
      reports of polyphyly of the genus Mycoplasma. As both clades of Mycoplasma
      contain several species of great practical importance, a change of the genus name
      for species in either clade would have immense practical implications. In
      addition, a change of the genus name for M. mycoides would have to be approved by
      the Judicial Commission. For these reasons, the Linnaean and phylogenetic
      classifications of Mycoplasma must for now be discrepant.

PMID- 15143042
TI  - Use of recA as an alternative phylogenetic marker in the family Vibrionaceae.
AB  - This study analysed the usefulness of recA gene sequences as an alternative
      phylogenetic and/or identification marker for vibrios. The recA sequences suggest
      that the genus Vibrio is polyphyletic. The high heterogeneity observed within
      vibrios was congruent with former polyphasic taxonomic studies on this group.
      Photobacterium species clustered together and apparently nested within vibrios,
      while Grimontia hollisae was apart from other vibrios. Within the vibrios, Vibrio
      cholerae and Vibrio mimicus clustered apart from the other genus members. Vibrio
      harveyi- and Vibrio splendidus-related species formed compact separated groups.
      On the other hand, species related to Vibrio tubiashii appeared scattered in the
      phylogenetic tree. The pairs Vibrio coralliilyticus and Vibrio neptunius, Vibrio
      nereis and Vibrio xuii and V. tubiashii and Vibrio brasiliensis clustered
      completely apart from each other. There was a correlation of 0.58 between recA
      and 16S rDNA pairwise similarities. Strains of the same species have at least 94
      % recA sequence similarity. recA gene sequences are much more discriminatory than
      16S rDNA. For 16S rDNA similarity values above 98 % there was a wide range of
      recA similarities, from 83 to 99 %.

PMID- 15143043
TI  - Corynebacterium caspium sp. nov., from a Caspian seal (Phoca caspica).
AB  - A previously unknown Gram-positive, non-spore-forming, non-lipophilic, catalase
      positive, irregular rod-shaped bacterium (M/106/00/5(T)) was isolated, in mixed
      culture, from the penis of a Caspian seal (Phoca caspica). The strain was a
      facultative anaerobe that was able to grow at 22 and 42 degrees C. Comparative
      16S rRNA gene sequencing showed that the organism formed a hitherto unknown
      subline within the genus Corynebacterium. Sequence divergence values of more than
      5 % from other described Corynebacterium species, together with phenotypic
      differences, showed that the unidentified bacterium represents a previously
      unrecognized member of this genus. On the basis of phenotypic and phylogenetic
      considerations, it is proposed that the unknown bacterium isolated from a Caspian
      seal (strain M/106/00/5(T)=CCUG 44566(T)=CIP 107965(T)) be classified as the type
      strain of a novel species of the genus Corynebacterium, Corynebacterium caspium
      sp. nov.

PMID- 15143045
TI  - Psychroflexus tropicus sp. nov., an obligately halophilic Cytophaga
      Flavobacterium-Bacteroides group bacterium from an Hawaiian hypersaline lake.
AB  - A Gram-negative bacterium designated LA1(T) was isolated from water collected in
      hypersaline Lake Laysan on Laysan Island in the Northwestern Hawaiian Islands.
      Cells occurred singly as fine rods to short filaments. Growth in 50 % strength
      marine broth occurred optimally when the medium contained 7.5-10 % (w/v) NaCl.
      The major fatty acids in LA1(T) grown at 15 and 30 degrees C were 12-methyl
      tetradecanoic acid and 13-methyl tetradecanoic acid, respectively. The nucleotide
      sequence of the 16S rRNA gene showed that LA1(T) belonged in the Cytophaga
      Flavobacterium-Bacteroides (CFB) group in the domain Bacteria. The closest
      described neighbour in terms of 16S rRNA gene sequence identity was Psychroflexus
      torquis ACAM 623(T) (94.4 % over 1423 bases), an obligate psychrophile from
      Antarctic sea-ice. The G+C content of 35.0 mol% was consistent with this
      affiliation. Phenotypic and genotypic analyses, including DNA hybridization,
      indicated that LA1(T) could be assigned to the genus Psychroflexus but, based on
      significant differences, including growth at 43 degrees C, it constitutes a novel
      species, Psychroflexus tropicus sp. nov., for which LA1(T) (=ATCC BAA-734(T)=DSM
      15496(T)) is the type strain.

PMID- 15143044
TI  - Transfer of Bacillus ehimensis and Bacillus chitinolyticus to the genus
      Paenibacillus with emended descriptions of Paenibacillus ehimensis comb. nov. and
      Paenibacillus chitinolyticus comb. nov.
AB  - The taxonomic status of Bacillus ehimensis and Bacillus chitinolyticus was
      examined, based on their 16S rDNA sequences, DNA-DNA hybridization and other
      taxonomic characteristics. A phylogenetic analysis using 16S rDNA sequences
      revealed that the two species belong to the genus Paenibacillus. In particular,
      B. ehimensis KCTC 3748(T) and B. chitinolyticus KCTC 3791(T) were found to be
      phylogenetically closely related to Paenibacillus koreensis YC300(T) (98.3 %
      sequence similarity) and Paenibacillus chinjuensis WN9(T) (95.2 % sequence
      similarity), respectively. DNA-DNA hybridization values between B. ehimensis KCTC
      3748(T) and P. koreensis YC300(T) were less than 26 %. An experiment using
      Paenibacillus-specific PCR primers, PAEN515F and 1377R, revealed that B.
      ehimensis and B. chitinolyticus had the same amplified 16S rDNA fragment as
      members of the genus Paenibacillus. Accordingly, it is proposed that B. ehimensis
      and B. chitinolyticus be transferred to the genus Paenibacillus as Paenibacillus
      ehimensis comb. nov. and Paenibacillus chitinolyticus comb. nov., respectively.

PMID- 15143047
TI  - Clostridium hastiforme is a later synonym of Tissierella praeacuta.
AB  - The previously proposed species Clostridium hastiforme and Tissierella praeacuta
      appear to be similar from their published descriptions. Accordingly, the aim of
      the current study was to perform phenotypic and genetic analyses of the type
      strains of both species, in order to clarify their taxonomic positions. The type
      strains of C. hastiforme (DSM 5675(T)) and T. praeacuta (NCTC 11158(T)) exhibited
      identical biochemical profiles and their 16S rRNA gene sequences displayed 99.9 %
      similarity. DNA-DNA hybridization was also estimated to be 96.5 %. Thus, it was
      concluded that C. hastiforme and T. praeacuta are synonyms, where T. praeacuta
      has priority. An emended description of the genus Tissierella is also given.

PMID- 15143046
TI  - Anoxybacillus contaminans sp. nov. and Bacillus gelatini sp. nov., isolated from
      contaminated gelatin batches.
AB  - Aerobic, endospore-forming bacteria that are attributed to the genus Bacillus or
      related genera constitute a hazard to the quality of gelatin. During repetitive
      extragenic palindromic DNA (rep)-PCR screening of gelatin isolates, a group of
      five isolates (group 1) and a group of 66 isolates (group 2) that did not match
      any pattern in our database were found. On the basis of 16S rDNA sequence
      analysis, representative strains of the different rep-PCR fingerprint types of
      group 1 were shown to be related most closely to Anoxybacillus species, but with
      sequence similarity of <97 %. Likewise, representative strains of group 2 were
      shown to be related most closely to Bacillus species, with 16S rDNA sequence
      similarity of <97 %. DNA-DNA reassociation values of isolates that displayed the
      most divergent rep-PCR profiles revealed that strains within each group belonged
      to a single species, according to recommendations for species delineation. A mean
      fatty acid profile could be calculated for each group. Isolates within a single
      group had similar patterns of results in API and other phenotypic tests; no
      correlation of patterns of results with rep-PCR groups was seen. Physiological
      characterization of group 1 isolates allows their distinction from other
      Anoxybacillus species. Despite the weak reaction of group 2 isolates in API
      tests, physiological characterization allows distinction between Bacillus species
      that react weakly in API tests. Two novel species are therefore proposed, with
      the names Anoxybacillus contaminans sp. nov. (type strain, LMG 21881(T)=DSM
      15866(T)) and Bacillus gelatini sp. nov. (type strain, LMG 21880(T)=DSM
      15865(T)).

PMID- 15143048
TI  - Propionispora hippei sp. nov., a novel Gram-negative, spore-forming anaerobe that
      produces propionic acid.
AB  - A Gram-negative, spore-forming anaerobe, KS(T), was isolated from an enrichment
      culture that was set up for anaerobic degradation of the aliphatic polyester
      poly(propylene adipate). The strain had the cellular organization of Sporomusa,
      vibrio-shaped cells and terminal round spores, and fermented sugars and sugar
      alcohols to propionic and acetic acid. Based on the morphological and
      physiological features as well as on a 16S rRNA gene similarity of 98 %, it was
      grouped with Propionispora vibrioides. A relatively low DNA-DNA hybridization
      value with the type strain of this species (47 %), and differences in substrate
      utilization and spore morphology, suggested that the strain should be classified
      in a separate species, Propionispora hippei sp. nov., with KS(T) as the type
      strain (=DSM 15287(T)=ATCC BAA-665(T)).

PMID- 15143049
TI  - Catellibacterium nectariphilum gen. nov., sp. nov., which requires a diffusible
      compound from a strain related to the genus Sphingomonas for vigorous growth.
AB  - A bacterial strain, designated AST4(T), was isolated from activated sludge. The
      bacterium did not show significant growth on nutrient broth, but growth was
      clearly stimulated by addition of supernatant from other bacterial cultures.
      Culture filtrate of a strain related to the genus Sphingomonas in particular
      increased the cell yield and growth rate of strain AST4(T). Phylogenetic analysis
      based on the 16S rRNA gene sequences showed that strain AST4(T) is located within
      the 'Rhodobacter group' in the alpha-3 subclass of Proteobacteria, but is clearly
      distant from related genera in this group such as Paracoccus, Rhodobacter and
      Rhodovulum. Strain AST4(T) is a Gram-negative, non-motile, rod-shaped (0.6
      0.8x1.3-2.0 micro m) and aerobic bacterium. It was not able to reduce nitrate to
      nitrite or N(2). No phototrophic growth was observed. Optimal growth occurred at
      30 degrees C and pH 6.5-7.5. The dominant cellular fatty acid in the isolate was
      C(18 : 1)cis11. Ubiquinone-10 was the major respiratory quinone. The G+C content
      was 64.5 mol% (by HPLC). Based on the phylogenetic and phenotypic traits, the
      name Catellibacterium nectariphilum gen. nov., sp. nov. is proposed for this
      isolate; the type strain is AST4(T) (=NBRC 100046(T)=JCM 11959(T)=DSM 15620(T)).

PMID- 15143050
TI  - Characterization of a 'Bacteroidetes' symbiont in Encarsia wasps (Hymenoptera:
      Aphelinidae): proposal of 'Candidatus Cardinium hertigii'.
AB  - Previously, analysis of 16S rDNA sequences placed a newly discovered lineage of
      bacterial symbionts of arthropods in the 'Bacteroidetes'. This symbiont lineage
      is associated with a number of diverse host reproductive manipulations, including
      induction of parthenogenesis in several Encarsia parasitoid wasps (Hymenoptera:
      Aphelinidae). In this study, electron microscopy and phylogenetic analysis of the
      16S rRNA and gyrB genes of symbionts from Encarsia hispida and Encarsia
      pergandiella are used to describe and further characterize these bacteria.
      Phylogenetic analyses based on these two genes showed that the Encarsia symbionts
      are allied with the Cytophaga aurantiaca lineage within the 'Bacteroidetes', with
      their closest described relative being the acanthamoeba symbiont 'Candidatus
      Amoebophilus asiaticus'. The Encarsia symbionts share 97 % 16S rDNA sequence
      similarity with Brevipalpus mite and Ixodes tick symbionts and 88 % sequence
      similarity with 'Candidatus A. asiaticus'. Electron microscopy revealed that many
      of the bacteria found in the ovaries of the two Encarsia species contained a
      regular, brush-like array of microfilament-like structures that appear to be
      characteristic of the symbiont. Finally, the role of this bacterium in
      parthenogenesis induction in E. hispida was confirmed. Based on phylogenetic
      analyses and electron microscopy, classification of the symbionts from Encarsia
      as 'Candidatus Cardinium hertigii' is proposed.

PMID- 15143051
TI  - Syntrophomonas curvata sp. nov., an anaerobe that degrades fatty acids in co
      culture with methanogens.
AB  - A strict anaerobe (strain GB8-1(T)) that degraded straight-chain fatty acids with
      C(4)-C(18) in syntrophic association with methanogens was isolated from an up
      flow anaerobic sludge blanket reactor treating beer wastewater. Strain GB8-1(T)
      degraded 1 mol butyrate into about 2 mol acetate and 1 mol (presumably) H(2) in
      co-culture with a methanogen. Neither branched-chain fatty acids nor benzoate
      could be degraded. Strain GB8-1(T) could grow on crotonate in pure culture and
      converted 1 mol crotonate to 0.5 mol butyrate and 1 mol acetate. Generation time
      was about 11 h when grown on crotonate at 37 degrees C. Fumarate, sulfate,
      thiosulfate, sulfur and nitrate could not serve as electron acceptors for strain
      GB8-1(T) to degrade butyrate. Cells of strain GB8-1(T) were curved rods with Gram
      negative cell walls; no spores were observed. The DNA G+C content was 46.6 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GB8
      1(T) was related most closely to the fatty acid-oxidizing, syntrophic bacterium
      Syntrophomonas sapovorans DSM 3441(T); however, the relationship was not very
      close (95.4 % sequence similarity). Some phenotypic features also differentiated
      strain GB8-1(T) from Syntrophomonas sapovorans DSM 3441(T). Therefore, a novel
      species, Syntrophomonas curvata sp. nov., is proposed. The type strain is GB8
      1(T) (=CGMCC 1.5010(T)=DSM 15682(T)).

PMID- 15143052
TI  - Systematics of the anamorphic basidiomycetous yeast genus Trichosporon Behrend
      with the description of five novel species: Trichosporon vadense, T. smithiae, T.
      dehoogii, T. scarabaeorum and T. gamsii.
AB  - Phylogenetic trees of the anamorphic basidiomycetous yeast genus Trichosporon
      Behrend, based on molecular sequence analysis of the internal transcribed spacer
      region and the D1/D2 region of the large subunit of ribosomal (26S) DNA, are
      presented. This study includes three novel species from soils, Trichosporon
      vadense sp. nov. (type strain, CBS 8901(T)), Trichosporon smithiae sp. nov. (type
      strain, CBS 8370(T)) and Trichosporon gamsii sp. nov. (type strain, CBS 8245(T)),
      one novel species from an insect, Trichosporon scarabaeorum sp. nov. (type
      strain, CBS 5601(T)) and one species of unknown origin, Trichosporon dehoogii sp.
      nov. (type strain, CBS 8686(T)). The phylogenetic positions and physiological
      characteristics that distinguish the new taxa from related species, based partly
      on growth tests that are not traditionally used in yeast taxonomy (uric acid,
      ethylamine, L-4-hydroxyproline, tyramine and L-phenylalanine as sources of carbon
      and nitrogen, and polygalacturonate, quinate, 4-ethylphenol, phloroglucinol, 2,3
      dihydroxybenzoate and orcinol as sole carbon sources), are discussed.
      Assimilation of L-rhamnose and erythritol and maximum growth temperature were
      also used to delineate species.

PMID- 15143053
TI  - Auriculibuller fuscus gen. nov., sp. nov. and Bullera japonica sp. nov., novel
      taxa in the Tremellales.
AB  - Seven phylloplane yeast strains that were collected in the Arrabida Natural Park,
      Portugal, and identified preliminarily as Bullera alba, the anamorphic stage of
      Bulleromyces albus, were investigated. In contrast to Bulleromyces albus, these
      isolates produced a brownish pigment when grown on potato dextrose agar. The
      pigment caused darkening of the cultures and diffused into the culture medium.
      Mating studies revealed that the Arrabida isolates did not react with the
      different mating types of Bulleromyces albus, but were sexually compatible with
      them and produced mycelium with clamp connections, haustoria and transversally
      septate basidia that ejected the basidiospores. Various taxonomic criteria that
      were evaluated during the present study and comparison with other sexual taxa of
      the Tremellales indicated that this teleomorph should be classified in a novel
      genus. Therefore, Auriculibuller fuscus gen. nov., sp. nov. (type strain, PYCC
      5690(T)=CBS 9648(T)) is proposed. In addition, during the course of this
      investigation, a member of a novel Bullera species, Bullera japonica sp. nov.
      (type strain, PYCC 4534(T)=CBS 2013(T)), was found among collection isolates that
      were identified formerly as Bullera alba. In molecular phylogenetic analysis of
      the D1/D2 domains of the 26S rDNA and the internal transcribed spacer region, the
      two taxa were found to be closely related, but distinct at the species level.

PMID- 15143054
TI  - Reassignment of the basidiomycetous yeasts Trichosporon pullulans to Guehomyces
      pullulans gen. nov., comb. nov. and Hyalodendron lignicola to Trichosporon
      lignicola comb. nov.
AB  - Nucleotide sequence analyses of the hymenomycetous yeasts demonstrated that
      Hyalodendron lignicola should be considered as a member of the genus Trichosporon
      within the Trichosporonales and that Trichosporon pullulans is associated closely
      with the Cystofilobasidiales, rather than the Trichosporonales. Accordingly, the
      following proposals are made: Trichosporon lignicola comb. nov. and Guehomyces
      gen. nov., to accommodate Guehomyces pullulans comb. nov. in the
      Cystofilobasidiales.

PMID- 15143055
TI  - Proposal of Nakamurella gen. nov. as a substitute for the bacterial genus
      Microsphaera Yoshimi et al. 1996 and Nakamurellaceae fam. nov. as a substitute
      for the illegitimate bacterial family Microsphaeraceae Rainey et al. 1997.
AB  - The bacterial genus Microsphaera Yoshimi et al. 1996 is illegitimate because of
      priority of the fungal genus Microsphaera (Wallr.) Lev. [Principle 2, Rule 51b(4)
      of the Bacteriological Code]. Therefore, a new genus name, Nakamurella, is
      proposed for the bacterial genus. The type species Microsphaera multipartita
      Yoshimi et al. 1996 becomes Nakamurella multipartita gen. nov., comb. nov. Due to
      the illegitimacy of the only genus in the family Microsphaeraceae Rainey et al.
      1997, this family name is replaced by the new bacterial family name
      Nakamurellaceae.

PMID- 15143057
TI  - Solution structure of atypical protein kinase C PB1 domain and its mode of
      interaction with ZIP/p62 and MEK5.
AB  - Atypical protein kinase C (aPKC) has been implicated in several signaling
      pathways such as cell polarity, cell survival, and cell differentiation. In
      contrast to other PKCs, aPKC is unique in having the PB1 (Phox and Bem 1) domain
      in the N terminus. The aPKC PB1 domain binds with ZIP/p62, Par6, or MEK5 through
      a PB1-PB1 domain interaction that controls the localization of aPKC. Here, we
      determined the three-dimensional structure of the PB1 domain of PKCiota by NMR
      and found that the PB1 domain adopts a ubiquitin fold. The OPCA (OPR, PC, and
      AID) motif inserted into the ubiquitin fold was presented as a betabetaalpha fold
      in which the side chains of conserved Asp residues were oriented to the same
      direction to form an acidic surface. This structural feature suggested that the
      acidic surface of the PKCiota PB1 domain interacted with the basic surface of the
      target PB1 domains, and this was confirmed in the case of the PKCiota-ZIP/p62
      complex by mutational analysis. Interestingly, in the PKCiota PB1 domain a
      conserved lysine residue was located on the side opposite to the OPCA motif
      presenting surface, suggesting dual roles for the PKCiota PB1 domain in that it
      could interact with either the conserved lysine residue or the acidic residues on
      the OPCA motif of the target PB1 domains.

PMID- 15143059
TI  - Structure and dynamics of a helical hairpin that mediates calcium-dependent
      membrane binding of annexin B12.
AB  - A wealth of high-resolution structural data has accumulated for soluble annexins,
      but only limited information is available for the biologically important membrane
      bound proteins. To investigate the structural and dynamic changes that occur upon
      membrane binding, we analyzed the electron paramagnetic resonance (EPR) mobility
      and accessibility parameters of a continuous 30-residue nitroxide scan
      encompassing helices D and E in repeat 2 of annexin B12 (residues 134-163) while
      the protein was bound to phospholipid vesicles in the presence of Ca(2+). A
      comparison of these data to those from a previously published study of the
      protein in solution (Isas, J. M., Langen, R., Haigler, H. T., and Hubbell, W. L.
      (2002) Biochemistry 41, 1464-1473) showed that the overall backbone fold for the
      scanned region did not change upon membrane binding. However, side-chains in the
      loop between the D and E helices were highly dynamic in solution but became
      essentially frozen in the EPR time scale upon binding to membranes. Accessibility
      measurements clearly established that side-chains in this loop were exposed to
      the hydrophobic core of the bilayer and provide the first evidence that a D-E
      loop directly participates in the Ca(2+)-dependent binding of annexins to
      membranes. Other localized changes showed that the D-helix became much less
      dynamic after membrane binding and identified quaternary contact sites in the
      membrane-bound homo-trimer. Finally, immobilization of the D-E loop upon contact
      with phospholipid suggests that the bilayer, which is normally very mobile on the
      EPR time scale, is immobilized in the head-group region by the annexin B12. This
      suggests that annexin B12 alters membrane structure in a manner that may be
      biologically significant.

PMID- 15143058
TI  - Redox-regulated turnover of Nrf2 is determined by at least two separate protein
      domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron.
AB  - The Nrf2 transcription factor is more rapidly turned over in cells grown under
      homeostatic conditions than in those experiencing oxidative stress. The variable
      turnover of Nrf2 is accomplished through the use of at least two degrons and its
      redox-sensitive interaction with the Kelch-repeat protein Keap1. In homeostatic
      COS1 cells, the Neh2 degron confers on Nrf2 a half-life of less than 10 min.
      Analyses of deletion mutants of a Gal4(HA)mNeh2 fusion protein and full-length
      mNrf2 indicate that full redox-sensitive Neh2 destabilizing activity depends upon
      two separate sequences within this N-terminal domain. The DIDLID element (amino
      acids 17-32) is indispensable for Neh2 activity and appears necessary to recruit
      a ubiquitin ligase to the fusion protein. A second motif within Neh2, the ETGE
      tetrapeptide (amino acids 79-82), allows the redox-sensitive recruitment of Nrf2
      to Keap1. This interaction, which occurs only in homeostatic cells, enhances the
      capacity of the Neh2 degron to direct degradation by functioning downstream of
      ubiquitination mediated by the DIDLID element. By contrast with the situation
      under homeostatic conditions, the Neh2 degron is neither necessary nor sufficient
      to account for the characteristic half-life of Nrf2 in oxidatively stressed
      cells. Instead, the previously uncharacterized, redox-insensitive Neh6 degron
      (amino acids 329-379) is essential to ensure that the transcription factor is
      still appropriately turned over in stressed cells, albeit with an increased half
      life of 40 min. A model can now be proposed to explain how the turnover of this
      protein adapts in response to alterations in cellular redox state.

PMID- 15143060
TI  - The trihelical bundle subdomain of the GGA proteins interacts with multiple
      partners through overlapping but distinct sites.
AB  - The Golgi-localized, gamma-adaptin ear-containing, ARF-binding (GGA) proteins are
      monomeric clathrin adaptors that mediate the sorting of cargo at the trans-Golgi
      network and endosomes. The GGAs contain four different domains named Vps27, Hrs,
      Stam (VHS); GGAs and TOM1 (GAT); hinge; and gamma-adaptin ear (GAE). The VHS
      domain recognizes transmembrane cargo, whereas the hinge and GAE regions bind
      clathrin and accessory proteins, respectively. The GAT domain is a polyfunctional
      module that interacts with various partners including the small GTPase ARF, the
      endosomal fusion regulator Rabaptin-5, ubiquitin, and the product of the tumor
      susceptibility gene 101 (TSG101). Previous x-ray crystallographic analyses showed
      that the GAT region is composed of two subdomains, an N-terminal helix-loop-helix
      containing the ARF binding site, and a C-terminal triple alpha-helical
      (trihelical) bundle. In this study, we define the Rabaptin-5 binding site on the
      GGA1-GAT domain and its relationship to the binding sites for ubiquitin and
      TSG101. Our observations show that Rabaptin-5, ubiquitin, and TSG101 bind to
      overlapping but distinct binding sites on the trihelical bundle. The different
      GAT binding partners engage in both competitive and cooperative interactions that
      may be important for the function of the GGAs in protein sorting.

PMID- 15143061
TI  - Competition for talin results in trans-dominant inhibition of integrin
      activation.
AB  - The ability of integrin adhesion receptors to undergo rapid changes in affinity
      for their extracellular ligands (integrin activation) is essential for the
      development and function of multicellular animals and is dependent on
      interactions between the integrin beta subunit-cytoplasmic tail and the
      cytoskeletal protein talin. Cross-talk among different integrins and between
      integrins and other receptors impacts many cellular processes including adhesion,
      spreading, migration, clot retraction, proliferation, and differentiation. One
      form of integrin cross-talk, transdominant inhibition of integrin activation,
      occurs when ligand binding to one integrin inhibits the activation of a second
      integrin. This may be relevant clinically in a number of settings such as during
      platelet adhesion, leukocyte trans-migration, and angiogenesis. Here we report
      that competition for talin underlies the trans-dominant inhibition of integrin
      activation. This conclusion is based on our observations that (i). beta tails
      selectively defective in talin binding are unable to mediate trans-dominant
      inhibition, (ii). trans-dominant inhibition can be reversed by overexpression of
      integrin binding and activating fragments of talin, and (iii). expression of
      another non-integrin talin-binding protein, phosphatidylinositol phosphate kinase
      type Igamma-90, also inhibits integrin activation. Thus, the sequestration of
      talin by the suppressive species is both necessary and sufficient for trans
      dominant inhibition of integrin activation.

PMID- 15143062
TI  - Oxidized phospholipids increase interleukin 8 (IL-8) synthesis by activation of
      the c-src/signal transducers and activators of transcription (STAT)3 pathway.
AB  - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and
      its component phospholipids 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3
      phosphorylcholine (PEIPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3
      phosphorylcholine induce endothelial cells to synthesize chemotactic factors,
      such as interleukin 8 (IL-8). We have shown recently that Ox-PAPC-mediated
      induction of IL-8 transcription is independent of NF-kappaB activation, a major
      transcription factor utilized by cytokines and lipopolysaccharide for the
      induction of IL-8 transcription. In this study, we provide evidence for the role
      of c-src in Ox-PAPC and, specifically, PEIPC-mediated IL-8 induction. Ox-PAPC and
      its component phospholipids induced a rapid and transient phosphorylation of c
      src Tyr418, a hallmark of c-src activation, in human aortic endothelial cells
      (HAEC). Ox-PAPC-mediated IL-8 protein synthesis in HAEC was inhibited by Src
      family kinase inhibitors, PP1 and PP2, but not by an inactive analog, PP3.
      Transient expression of plasmids containing C-terminal Src kinase or kinase
      deficient dominant-negative c-src resulted in a 72 and 50% reduction in Ox-PAPC
      induced IL-8 promoter activation in human microvascular endothelial cells,
      respectively. In contrast, overexpression of v-src kinase resulted in a 4-fold
      increase in IL-8 promoter activation, without inducing NF-kappaB promoter
      activation. Furthermore, treatment of HAEC with Ox-PAPC and its component PEIPC
      induced the activation of STAT3 by phosphorylating Tyr705, a feature of STAT3
      activation. STAT3 is a known downstream effector of c-src. Ox-PAPC-induced
      activation of STAT3 resulted in the translocation of STAT3 from the cytoplasm of
      HAEC into their nuclear compartment. Transient expression of a dominant-negative
      STAT3beta construct in HMEC strongly inhibited IL-8 induction by Ox-PAPC. Taken
      together, these data demonstrate the role of the c-src kinase/STAT3 pathway in Ox
      PAPC-mediated IL-8 expression in endothelial cells.

PMID- 15143063
TI  - NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation.
AB  - Activation of the transcription factor NF-kappaB is a hallmark of infections by
      viral pathogens including influenza viruses. Because gene expression of many
      proinflammatory and antiviral cytokines is controlled by this factor, the concept
      emerged that NF-kappaB and its upstream regulator IkappaB kinase are essential
      components of the innate antiviral immune response to infectious pathogens. In
      contrast to this common view we report here that NF-kappaB activity promotes
      efficient influenza virus production. On a molecular level this is due to NF
      kappaB-dependent viral induction of the proapoptotic factors tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) and FasL, which enhance virus
      propagation in an autocrine and paracrine fashion. Thus, NF-kappaB acts both
      proapoptotically and provirally in the context of an influenza virus infection.

PMID- 15143064
TI  - The coupling of tight DNA binding and base flipping: identification of a
      conserved structural motif in base flipping enzymes.
AB  - Val(121) is positioned immediately above the extrahelical cytosine in HhaI DNA
      C(5)-cytosine methyltransferase, and replacement with alanine dramatically
      interferes with base flipping and catalysis. DNA binding and k(cat) are decreased
      10(5)-fold for the Val(121) --> Ala mutant that has a normal circular dichroism
      spectrum and AdoMet affinity. The magnitude of this loss of function is
      comparable with removal of the essential catalytic Cys(81). Surprisingly, DNA
      binding is completely recovered (increase of 10(5)-fold) with a DNA substrate
      lacking the target cytosine base (abasic). Thus, interfering with the base
      flipping transition results in a dramatic loss of binding energy. Our data
      support an induced fit mechanism in which tight DNA binding is coupled to both
      base flipping and protein loop rearrangement. The importance of the proximal
      protein segment (His(127)-Thr(132)) in maintaining this critical interaction
      between Val(121) and the flipped cytosine was probed with single site alanine
      substitutions. None of these mutants are significantly altered in secondary
      structure, AdoMet or DNA affinity, k(methylation), k(inactivation), or k(cat).
      Although Val(121) plays a critical role in both extrahelical base stabilization
      and catalysis, its position and mobility are not influenced by individual
      residues in the adjacent peptide region. Structural comparisons with other DNA
      methyltransferases and DNA repair enzymes that stabilize extrahelical nucleotides
      reveal a motif that includes a positively charged or polar side chain and a
      hydrophobic residue positioned adjacent to the target DNA base and either the 5'-
      or 3'-phosphate.

PMID- 15143065
TI  - Regulation and function of the calcium/calmodulin-dependent protein kinase
      IV/protein serine/threonine phosphatase 2A signaling complex.
AB  - Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a member of the broad
      substrate specificity class of Ca(2+)/calmodulin (CaM)-dependent protein kinases
      and functions as a potent stimulator of Ca(2+)-dependent gene expression.
      Activation of CaMKIV is a transient, tightly regulated event requiring both
      Ca(2+)/CaM binding and phosphorylation of the kinase on T200 by an upstream CaMK
      kinase (CaMKK). Previously, CaMKIV was shown to stably associate with protein
      serine/threonine phosphatase 2A (PP2A), which was proposed to play a role in
      negatively regulating the kinase. Here we report that the Ca(2+)/CaM binding
      autoinhibitory domain of CaMKIV is required for association of the kinase with
      PP2A and that binding of PP2A and Ca(2+)/CaM appears to be mutually exclusive. We
      demonstrate that inhibition of the CaMKIV/PP2A association in cells results in
      enhanced CaMKIV-mediated gene transcription that is independent of Ca(2+)/CaM.
      The enhanced transcriptional activity correlates with the elevated level of
      phospho-T200 that accumulates when CaMKIV is prevented from interacting with
      PP2A. Collectively, these data suggest a molecular basis for the sequential
      activation and inactivation of CaMKIV. First, in response to an increase in
      intracellular Ca(2+), CaMKIV binds Ca(2+)/CaM and becomes phosphorylated on T200
      by CaMKK. These events result in the generation of autonomous activity required
      for CaMKIV-mediated transcriptional regulation. The CaMKIV-associated PP2A then
      dephosphorylates CaMKIV T200, thereby terminating autonomous activity and CaMKIV
      mediated gene transcription.

PMID- 15143066
TI  - Isotype-specific degradation of Rac activated by the cytotoxic necrotizing factor
      1.
AB  - The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli activates members
      of the Rho family by deamidation of glutamine 61/63. Because this amino acid is
      crucial for GTP hydrolysis, deamidation of glutamine 61/63 results in
      constitutively active Rho proteins. Recently, it was shown that the level of CNF1
      activated Rac is rapidly diminished in CNF1-treated cells by proteolytic
      degradation. Here, we studied the requirements for CNF1-induced Rac degradation.
      By overexpressing His-tagged activated Rac mutants we show that constitutive
      activation is necessary for degradation of Rac. However, permanent activation is
      not sufficient for degradation, because Rac that is constitutively activated by
      transamidation at glutamine 61 by the Bordetella dermonecrotic toxin is not
      degraded. Overexpression of His-tagged Rac mutants deficient in interaction with
      GTPase-activating protein (Rac(N92D) and Rac(Y64H)) and guanosine nucleotide
      dissociation inhibitor (Rac(H103E)) were degraded after activation by CNF1,
      whereas Rac(Y40C), which is not able to interact with CRIB domain effectors or
      plenty of SH3, was not degraded. Isoprenylation and the presence of a putative
      mitotic destruction box are essential for CNF-induced degradation. In contrast to
      Rac1, Rac2, and Rac3 were not degraded following constitutive activation by CNF1.
      Using site-directed mutagenesis, we defined the polybasic region and amino acids
      90, 107, 147, and 151 as responsible for isotype-specific degradation.

PMID- 15143067
TI  - Altered proglucagon processing in an alpha-cell line derived from prohormone
      convertase 2 null mouse islets.
AB  - The endoproteolytic processing of proproteins in the secretory pathway depends on
      the expression of selected members of a family of subtilisin-like endoproteases
      known as the prohormone convertases (PCs). The main PC family members expressed
      in mammalian neuroendocrine cells are PC2 and PC1/3. The differential processing
      of proglucagon in pancreatic alpha-cells and intestinal L cells leads to
      production of distinct hormonal products with opposing physiological effects from
      the same precursor. Here we describe the establishment and characterization of a
      novel alpha-cell line (alphaTC-DeltaPC2) derived from PC2 homozygous null
      animals. The alphaTC-DeltaPC2 cells are shown to be similar to the well
      characterized alphaTC1-6 cell line in both morphology and overall gene
      expression. However, the absence of PC2 activity in alphaTC-DeltaPC2 leads to a
      complete block in the production of mature glucagon. Surprisingly, alphaTC
      DeltaPC2 cells are able to efficiently cleave the interdomain site in proglucagon
      (KR 70-71). Further analysis reveals that alphaTC-DeltaPC2 cells, unlike alphaTC1
      6 cells, express low levels of PC1/3 that lead to the generation of glicentin as
      well as low amounts of oxyntomodulin, GLP-1, truncated GLP-1, and N-terminally
      extended GLP-2. We conclude that alphaTC-DeltaPC2 cells provide additional
      evidence for PC2 as the major convertase in alpha-cells leading to mature
      glucagon production and provide a robust model for further analysis of the
      mechanisms of proprotein processing by the prohormone convertases.

PMID- 15143068
TI  - Cell growth regulation through GM3-enriched microdomain (glycosynapse) in human
      lung embryonal fibroblast WI38 and its oncogenic transformant VA13.
AB  - Cell growth control mechanisms were studied based on organization of components
      in glycosphingolipid-enriched microdomain (GEM) in WI38 cells versus their
      oncogenic transformant VA13 cells. Levels of fibroblast growth factor receptor
      (FGFR) and cSrc were 4 times and 2-3 times higher, respectively, in VA13 than in
      WI38 GEM, whereas the level of tetraspanin CD9/CD81 was 3-5 times higher in WI38
      than in VA13 GEM. Csk, the physiological inhibitor of cSrc, was present in WI38
      but not in VA13 GEM. Functional association of GEM components in control of cell
      growth in WI38 is indicated by several lines of evidence. (i) Confluent, growth
      inhibited WI38 showed a lower degree of FGF-induced MAPK activation than actively
      growing cells in sparse culture. (ii) The level of inactive cSrc (with Tyr-527
      phosphate) was higher in confluent cells than in actively growing cells. Both
      processes i and ii were inhibited by GM3 since they were enhanced by GM3
      depletion with d-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4).
      (iii) The high level of inactive cSrc associated with growth-inhibited cells was
      caused by coexisting Csk in WI38 GEM. (iv) Interaction of GM3 with FGFR was
      demonstrated by binding of GM3 to FGFR in the GEM fraction, as probed with GM3
      coated beads, and by confocal microscopy. In contrast to WI38, both cSrc and MAPK
      in VA13 were strongly activated regardless of FGF stimulation or GM3 depletion by
      P4. Continuous, constitutive activation of both cSrc and MAPK was due to (i) a
      much higher level of cSrc and FGFR in VA13 than in WI38 GEM, (ii) their close
      association/interaction in VA13 GEM as indicated by clear coimmunoprecipitation
      between cSrc and FGFR, and (iii) the absence of Csk in VA13 GEM, making GEM
      incapable of inhibiting cSrc activation.

PMID- 15143069
TI  - Transforming growth factor-beta1 stimulates vascular endothelial growth factor
      164 via mitogen-activated protein kinase kinase 3-p38alpha and p38delta mitogen
      activated protein kinase-dependent pathway in murine mesangial cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent inducer of extracellular
      matrix synthesis leading to progressive glomerular fibrosis. The intracellular
      signaling mechanisms involved in this process remain incompletely understood. The
      p38 mitogen-activated protein kinase (MAPK) is a major stress signal transducing
      pathway that is rapidly activated by TGF-beta1 in mesangial cells. We have
      previously demonstrated MKK3 as the immediate upstream MAPK kinase required for
      selective activation of p38 MAPK isoforms, p38alpha and p38delta, and stimulation
      of pro-alpha1(I) collagen by TGF-beta1 in murine mesangial cells. In this study,
      we further sought to determine MAPK kinase 3 (MKK3)-dependent TGF-beta1 responses
      by gene expression profiling analysis utilizing mesangial cells isolated from
      Mkk3-/- mice compared with Mkk3+/+ controls. Interestingly, vascular endothelial
      growth factor (VEGF) was identified as a TGF-beta1-induced gene affected by
      deletion of Mkk3. VEGF is a well known endothelial mitogen, whose actions in
      nonendothelial cell types are still not well understood. We confirmed that TGF
      beta1 increased VEGF mRNA and protein synthesis of VEGF164 and VEGF188 isoforms
      in wild-type mesangial cells. However, in the Mkk3-/- mesangial cells, both TGF
      beta1-induced VEGF mRNA and VEGF164 protein expression were inhibited, whereas
      TGF-beta1-induced VEGF188 protein expression was unaffected. Furthermore,
      transfection of dominant negative mutants of p38alpha and p38delta resulted in
      marked inhibition of TGF-beta1-induced VEGF164 expression but not VEGF188, and
      treatment with recombinant mouse VEGF164 increased collagen and fibronectin mRNA
      expression in mesangial cells. Taken together, our findings suggest a critical
      role for the MKK3-p38alpha and p38delta MAPK pathway in mediating VEGF164 isoform
      specific stimulation by TGF-beta1 in mesangial cells. Further, VEGF164 stimulates
      collagen and fibronectin expression in mesangial cells and thus in turn enhances
      TGF-beta1-induced extracellular matrix and may play an important role in
      progressive glomerular fibrosis.

PMID- 15143070
TI  - Maturation of human tripeptidyl-peptidase I in vitro.
AB  - Tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal aminopeptidase that
      cleaves off tripeptides from the free N termini of oligopeptides and also shows
      minor endopeptidase activity. TPP I is synthesized as a preproenzyme. Its
      proenzyme autoactivates under acidic conditions in vitro, resulting in a rapid
      conversion into the mature form. In this study, we examined the process of
      maturation in vitro of recombinant latent human TPP I purified to homogeneity
      from secretions of Chinese hamster ovary cells overexpressing TPP I cDNA.
      Autoprocessing of TPP I proenzyme was carried out at a wide pH range, from
      approximately 2.0 to 6.0, albeit with different efficiencies depending on the pH
      and the type of buffer. However, the acquisition of enzymatic activity in the
      same buffer took place in a narrower pH "window," usually in the range of 3.6
      4.2. N-terminal sequencing revealed that mature, inactive enzyme generated during
      autoactivation at higher pH contained N-terminal extensions (starting at 6 and 14
      amino acid residues upstream of the prosegment/mature enzyme junction), which
      could contribute to the lack of activity of TPP I generated in this manner.
      Autoprocessing was not associated with any major changes of the secondary
      structure of the proenzyme, as revealed by CD spectroscopy. Both the activation
      and proteolytic processing of the recombinant TPP I precursor were primarily
      concentration-independent. The addition of the mature enzyme did not accelerate
      the processing of the proenzyme. In addition, the maturation of the proenzyme was
      not affected by the presence of glycerol. Finally, the proenzyme with the active
      site mutated (S475L) was not processed in the presence of the wild-type enzyme.
      All of these findings indicate a primarily intramolecular (unimolecular)
      mechanism of TPP I activation and autoprocessing and suggest that in vivo mature
      enzyme does not significantly participate in its own generation from the
      precursor.

PMID- 15143071
TI  - R-cadherin influences cell motility via Rho family GTPases.
AB  - Classical cadherins are the transmembrane proteins of the adherens junction and
      mediate cell-cell adhesion via homotypic interactions in the extracellular space.
      In addition, they mediate connections to the cytoskeleton by means of their
      association with catenins. Decreased cadherin-mediated adhesion has been
      implicated as an important component of tumorigenesis. Cadherin switching is
      central to the epithelial to mesenchymal transitions that drive normal
      developmental processes. Cadherin switching has also been implicated in
      tumorigenesis, particularly in metastasis. Recently, cadherins have been shown to
      be engaged in cellular activities other than adhesion, including motility,
      invasion, and signaling. In this study, we show that inappropriate expression of
      R-cadherin in tumor cells results in decreased expression of endogenous cadherins
      (cadherin switching) and sustained signaling through Rho GTPases. In addition, we
      show that R-cadherin induces cell motility when expressed in epithelial cells and
      that this increased motility is dependent upon Rho GTPase activity.

PMID- 15143073
TI  - Telomere length and human telomerase reverse transcriptase expression as markers
      for progression and prognosis of colorectal carcinoma.
AB  - PURPOSE: Maintenance of telomeres through reactivation of telomerase is a
      prerequisite for tumors to preserve their ability to proliferate. The purpose of
      this study was to evaluate telomere length and human telomerase reverse
      transcriptase (hTERT) expression as markers for progression and prognosis of
      colorectal carcinoma. PATIENTS AND METHODS: Telomere length and hTERT expression
      were analyzed in matched cancer and adjacent noncancer mucosa samples from 57
      patients with R0-resected colorectal carcinoma. The median follow-up time was 76
      months. RESULTS: Telomere length and hTERT expression correlated significantly in
      cancer tissues and adjacent mucosa samples (r = 0.52, P <.001; and r = 0.54, P
      <.001, respectively). Overall, cancer tissue had shorter telomeres than adjacent
      mucosa (P <.001). Only in noncancer tissue did telomere length decrease with age
      (r = 0.36; P <.01). Telomere length in cancer tissue was significantly correlated
      with tumor stage (P <.01), with longer telomeres in advanced tumors. Patients
      with ratios of telomere length in cancer to noncancer tissue greater than 0.90
      had a significantly poorer overall survival compared with patients with smaller
      telomere length ratios (P <.002). In multivariate analysis, the telomere length
      ratio proved to be of independent prognostic value (P <.03). CONCLUSION:
      Telomeres in colorectal carcinoma tissue were significantly shorter compared with
      adjacent normal mucosa as an indication for extensive cell proliferation. The
      correlation with tumor stage and patient survival suggest that hTERT-mediated
      telomere stabilization may be critical for progression and prognosis of
      colorectal carcinoma.

PMID- 15143072
TI  - Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate
      cancer cells.
AB  - Thrombin and lysophosphatidic acid (LPA) receptors play important roles in
      vascular biology, development, and cancer. These receptors activate rho via
      G(12/13) family heterotrimeric G proteins, which are known to directly activate
      three distinct rho guanine nucleotide exchange factors (rhoGEFs) that contain a
      regulator of G protein signaling (RGS) domain (RGS-rhoGEFs). However, it is not
      known which, if any, of these RGS-rhoGEFs (LARG (leukemia-associated rhoGEF),
      p115rhoGEF, or PDZrhoGEF) plays a role in G protein-coupled receptor-stimulated
      rho signaling. Using oligonucleotide small interfering RNAs that suppress
      specific RGS-rhoGEF expression, we show that thrombin receptor stimulation of rho
      is primarily mediated by LARG in HEK293T and PC-3 prostate cancer cell lines. In
      contrast, the LPA-stimulated rho response in PC-3 cells is dependent on PDZrhoGEF
      expression. Suppression of p115rhoGEF had no effect. Thus different rhoGEFs (LARG
      and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA
      receptors.

PMID- 15143075
TI  - Quantitative DNA fingerprinting may distinguish new primary breast cancer from
      disease recurrence.
AB  - PURPOSE: Approximately 10% of women with breast cancer develop a second breast
      tumor, either a new primary or a recurrence. Differentiating between these
      entities using standard clinical and pathologic criteria remains challenging.
      Ambiguous cases arise, and misclassifications may occur. We investigated whether
      quantitative DNA fingerprinting, based on allele imbalance (AI) or loss of
      heterozygosity (LOH), could evaluate clonality and distinguish second primary
      breast cancer from recurrence. METHODS: We developed a scoring system based on
      the AI/LOH fingerprints of 20 independent breast tumors and generated a decision
      rule to classify any breast tumor pair as related or unrelated. We validated this
      approach on eight related tumors (cancers and synchronous positive lymph nodes).
      Finally, we analyzed paired tumors from 13 women (bilateral cancers, primary
      tumors and contralateral positive axillary lymph nodes, or two ipsilateral
      tumors). Each pair's genetic classification was compared with their clinical
      diagnosis and outcome. RESULTS: Each independent cancer had a unique fingerprint.
      Every tumor pair's relationship was quantifiable. Six of eight related tumor
      pairs were genetically classified correctly, two were indeterminate, and none
      were misclassified. Among the 13 women with two cancers, four of five clinically
      indeterminate pairs could be classified genetically. In three of 13 women, the
      pair's classification contradicted the clinical diagnosis. These women had
      bilateral cancers genetically classified as related and disease progression. This
      challenges the paradigm that bilateral cancers represent independent tumors.
      Overall, women with tumors genetically classified as related had poorer outcomes.
      CONCLUSION: Quantitative AI/LOH fingerprinting is a potentially valuable tool to
      improve diagnosis and optimize treatment for the growing number of second breast
      malignancies.

PMID- 15143074
TI  - Pegylated arginine deiminase treatment of patients with unresectable
      hepatocellular carcinoma: results from phase I/II studies.
AB  - PURPOSE: Recently, we reported that a large number of human hepatocellular cancer
      (HCC) cell lines were auxotrophic for arginine. Here we report the results
      obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated
      to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma
      arginine to treat HCC. The study was a cohort dose-escalation phase I/II study.
      PATIENTS AND METHODS: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw
      dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting
      level of approximately 130 micromol/L to below the level of detection (< 2
      micromol/L) for more than 7 days, a dose later defined as the optimal biologic
      dose. All patients were to receive three cycles at the optimum biologic dose.
      RESULTS: This therapy was well tolerated, even in patients who had no detectable
      plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled,
      two had a complete response, seven had a partial response, seven had stable
      disease, and three had progressive disease. The median survival for the 19
      patients enrolled on this study was 410 days, with four patients still alive at
      present (> 680 days). CONCLUSION: Elimination of all detectable plasma arginine
      in patients with HCC was well tolerated and seemed to be effective in the
      treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a
      larger population of individuals with HCC as well as other human tumors
      auxotrophic for arginine is warranted.

PMID- 15143076
TI  - Prognostic indicators and survival in patients with stage IIIB inflammatory
      breast carcinoma after dose-intense chemotherapy.
AB  - PURPOSE: To improve treatment outcome for patients presenting with inflammatory
      breast cancer (IBC), we have sequentially developed and tested single and tandem
      dose-intense chemotherapy regimens (DICT). Tumor- and treatment-related factors
      were analyzed to generate a prognostic model. PATIENTS AND METHODS: Between May
      1989 and April 2002, 120 patients received conventional-dose chemotherapy,
      surgery, and sequentially developed single- or tandem-cycle DICT. Disease- and
      treatment-specific features were subjected to univariate and multivariate
      analysis to correlate with outcome. RESULTS: At a median follow-up of 61 months
      (range, 21 to 161 months), estimated 5-year relapse-free survival (RFS) and
      overall survival (OS) were 44% (95% CI, 34% to 53%) and 64% (95% CI, 55% to 73%),
      respectively. In an age-adjusted multivariate analysis, RFS was better in
      patients with estrogen receptor (ER)/progesterone receptor (PR)-positive tumors
      (P =.002), for patients with fewer than four involved axillary nodes before DICT
      (P =.01), and in patients treated with radiation therapy (P =.001) and tandem
      DICT (P =.049). OS was improved in patients with ER/PR-positive tumors (P =.002),
      in those with fewer than four involved axillary nodes before DICT (P =.03), and
      in patients treated with radiation therapy (P =.002). CONCLUSION: This
      retrospective analysis suggests that either single or tandem DICT can be
      administered safely and may benefit selected patients with stage IIIB IBC. Those
      with receptor-negative IBC and with four or more involved axillary nodes before
      DICT need improved neoadjuvant and postadjuvant intensification therapy. A
      prospective randomized trial of single versus tandem DICT would be required to
      confirm the potential benefit of tandem DICT in the setting of IBC.

PMID- 15143077
TI  - Functional impact of breast cancer by age at diagnosis.
AB  - PURPOSE: To explore changes in physical and psychosocial function before and
      after breast cancer by age at diagnosis. PATIENTS AND METHODS: A total of 122,969
      women from the Nurses' Health Study (NHS) and NHS 2, ages 29 to 71 years, who
      responded to pre- and postfunctional status assessments were included; 1,082
      women were diagnosed with breast cancer between 1992 and 1997. Functional status
      was measured using the Medical Outcomes Study Short Form 36 (SF-36). Mean change
      in health-related quality of life (HRQoL) scores was computed across categories
      representing the combination of incident breast cancer (yes or no) and age at
      diagnosis (< or = 40, 41 to 64, or 65+ years). RESULTS: Compared with women < or
      = 40 years without breast cancer, women with breast cancer experienced
      significant functional declines. Young (age < or = 40) women who developed breast
      cancer experienced the largest relative declines in HRQoL (as compared with
      middle-aged and elderly women) in multiple domains including physical roles (
      18.8 v -11.5 and -7.5 points, respectively), bodily pain (-9.0 v -2.7 and -2.7
      points), social functioning (-11.3 v -4.3 and -4.4 points) and mental health (
      3.1 v 0.0 and +0.4 points). Much of the decline in HRQoL among elderly (age > or
      = 65) women with breast cancer was age related. CONCLUSION: Young women may fare
      worse than middle-aged or elderly women in both physical and psychosocial
      dimensions after breast cancer diagnosis. The needs of women facing breast cancer
      may be better understood within a life stage framework.

PMID- 15143078
TI  - Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults.
AB  - PURPOSE: To assess the cardiac status of the long-term survivors and to estimate
      the incidence and the features of subclinical cardiotoxicity induced after
      conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's
      lymphoma. PATIENTS AND METHODS: We analyzed a group of patients who previously
      received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were
      performed at least 5 years after therapy with anthracyclines. Clinical
      cardiomyopathy was defined by the presence of clinical signs of congestive heart
      failure (CHF). Subclinical cardiomyopathy was defined by decrease of left
      ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative
      dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or
      total-body irradiation), autologous stem-cell transplantation, high-dose
      cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes,
      hypercholesterolemia, familial history of cardiac disease, being overweight, and
      smoking history) were evaluated as potential risk factors for the development of
      cardiac dysfunction. RESULTS: Of 141 assessable patients (median age, 54 years;
      median cumulative dose of doxorubicin, 300 mg/m(2)), only one developed CHF.
      Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate
      analysis, factors that contributed to decreased FS were male sex (P <.01), older
      age (P <.01), higher cumulative dose of doxorubicin or association with another
      anthracycline (P =.04), radiotherapy (P =.04), and being overweight (P =.04).
      CONCLUSION: Cardiac abnormalities can occur in patients treated with doxorubicin
      for lymphoma in the absence of CHF, even in patients who received moderate
      anthracycline doses. Male sex, older age, higher dose of doxorubicin,
      radiotherapy, and being overweight were risk factors for the development of
      cardiomyopathy.

PMID- 15143079
TI  - Results of a phase II study of weekly paclitaxel plus carboplatin in patients
      with extensive small-cell lung cancer with Eastern Cooperative Oncology Group
      Performance Status of 2, or age > or = 70 years.
AB  - PURPOSE: To determine the 1-year survival, response rate (RR), time to
      progression (TTP), and safety of weekly paclitaxel plus carboplatin (PC) in
      patients with extensive small-cell lung cancer (ESCLC) with an Eastern
      Cooperative Performance Status performance status (PS) of 2 or an age > or = 70
      years. PATIENTS AND METHODS: Patients were treated with PC (paclitaxel 80 mg/m(2)
      and carboplatin area under the curve = 2) by intravenous infusion on days 1, 8,
      and 15 of every 4-week cycle for up to six cycles. RESULTS: Between July 2000 and
      December 2001, 77 eligible patients (50.6% were male, 97.4% were white, 44.2% had
      PS of 2, with median age of 74 years) with ESCLC were enrolled. Among the 66
      patients who were assessable for response, 25 responded to treatment (one
      complete response and 24 partial responses), for an objective RR of 38%. There
      were eight cases of stable disease (12.1%) and 33 cases of progressive disease
      (50%). The median survival was 7.2 months (range, < 1 to 24.4 months), and the
      estimated 1-year survival rate was 30%. The median TTP was 3.5 months (range, < 1
      to 21.2 months), and the estimated 1-year progression-free survival rate was 8%.
      The median duration of response was 4.5 months (range, 1.6 to 17.5 months). One
      death (sepsis) was possibly related to the study drugs. Grades 3 and 4 toxicities
      experienced by > or = 5% of patients included neutropenia (22.1%), fatigue
      (8.6%), anemia (5.2%), and nausea/vomiting (5.2%). CONCLUSION: This regimen
      produced relatively few toxicities (only two of the 66 assessable patients
      received fewer than two cycles because of toxicity), and both the median and 1
      year survival were similar to other regimens. This regimen may be a preferable
      treatment choice for patients with ESCLC who have a poor PS or who are aged > or
      = 70 years.

PMID- 15143080
TI  - RRM1 and PTEN as prognostic parameters for overall and disease-free survival in
      patients with non-small-cell lung cancer.
AB  - PURPOSE: RRM1 has important functions in the determination of the malignant
      phenotype. It controls cell proliferation through deoxynucleotide production and
      metastatic propensity through PTEN induction. It is located in a region of loss
      of heterozygosity in non-small-cell lung cancer (NSCLC), which is a predictor of
      poor survival. We hypothesized that RRM1 expression would be a significant
      predictor of outcome in NSCLC. PATIENTS AND METHODS: A retrospective data set of
      49 patients and a prospective data set of 77 patients with resectable NSCLC were
      studied. RNA was extracted from tumor and normal lung tissue, and expression of
      the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative
      polymerase chain reaction. RESULTS: RRM1 expression was significantly correlated
      with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor
      tissue was highly predictive of overall (P =.011 and.018, respectively) and
      disease-free survival (P =.002 and.026, respectively). Patients with high levels
      of expression lived longer and had disease recurrence later than patients with
      low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was
      predictive of long survival independent of tumor stage, performance status, and
      weight loss. CONCLUSION: RRM1 is a biologically and clinically important
      determinant of malignant behavior in NSCLC. Knowing the level of expression of
      this gene adds significant information to management decisions independent of the
      currently used outcome predictors of tumor stage, performance status, and weight
      loss. Future clinical trials should stratify patients based on expression of this
      gene to avoid unwanted biases.

PMID- 15143081
TI  - Combined use of erythropoietin and granulocyte colony-stimulating factor does not
      decrease blood transfusion requirements during induction therapy for high-risk
      neuroblastoma: a randomized controlled trial.
AB  - PURPOSE: To evaluate the efficacy of recombinant erythropoietin (EPO) and
      granulocyte colony-stimulating factor (G-CSF) in reducing blood transfusion
      requirements and stimulating hematopoiesis in children with high-risk
      neuroblastoma. PATIENTS AND METHODS: Thirty-eight patients given six cycles of
      intensive induction chemotherapy for high-risk neuroblastoma were randomized to
      receive G-CSF (n = 20) or G-CSF + EPO (n = 18). Cytokines were given
      subcutaneously each day, starting 24 hours after each chemotherapy cycle and
      continuing until 48 hours before the start of the next cycle. The primary end
      point was the effect of EPO on total red cell transfusion requirements during
      induction therapy. RESULTS: Patients who received G-CSF + EPO had a higher red
      cell transfusion requirement (median, 161.0 mL/kg) than did those who received G
      CSF alone (median, 106.6 mL/kg; P =.005). In addition, among patients given
      transfusions for hemoglobin < or = 8 g/dL, those in the G-CSF + EPO group
      received more red cell transfusions than did those given G-CSF alone (median per
      patient, 10 v 8, respectively; P =.044). The two treatment groups had similar
      cumulative durations of neutropenia, incidences of febrile neutropenia, platelet
      transfusion requirements, and numbers of platelet transfusions; they also
      received induction chemotherapy for similar durations and had similar
      probabilities of progression-free survival and overall survival. CONCLUSION: The
      addition of EPO to the G-CSF regimen provides no benefit for patients receiving
      intensive induction chemotherapy for high-risk neuroblastoma.

PMID- 15143082
TI  - Age is a risk factor for chemotherapy-induced hepatopathy with vincristine,
      dactinomycin, and cyclophosphamide.
AB  - PURPOSE: To evaluate the spectrum of and determine the risk factors for the
      development of liver toxicity (hepatopathy) after therapy with vincristine,
      dactinomycin, and cyclophosphamide (VAC) for rhabdomyosarcoma in children and
      adolescents. PATIENTS AND METHODS: We prospectively captured all events of
      hepatopathy occurring on the ongoing Children's Oncology Group intermediate risk
      protocol, D9803, for children with rhabdomyosarcoma. Patients enrolled onto this
      trial were randomly assigned to receive either VAC alone or VAC alternating with
      vincristine, topotecan, and cyclophosphamide. In addition, we reviewed the
      toxicity database and requested additional information for all patients with
      elevated bilirubin or transaminase levels. Risk factors were analyzed. RESULTS:
      Of 339 patients enrolled through August 2002, 18 developed hepatopathy. All
      events were captured by mandated toxicity reporting and filing of MedWatch forms,
      with no additional cases found after the additional search of the database. Four
      children died after developing this toxicity. All cases occurred after cycles of
      VAC (n = 16) or vincristine and cyclophosphamide with concomitant abdominal
      radiotherapy (n = 2). The onset of hepatopathy was 5 to 16 days from the start of
      a treatment cycle. For the 89 patients under 36 months of age, the risk of
      hepatopathy was 15%, with two deaths. For the 239 children 3 years of age or
      older, the risk for hepatopathy was 4%, with two deaths. CONCLUSION: The greatest
      risk factor for development of hepatopathy after VAC therapy was age. Dose
      modifications for younger children receiving VAC therapy are recommended.

PMID- 15143083
TI  - Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a
      report of group III patients on the third Intergroup Rhabdomyosarcoma Study.
AB  - PURPOSE: To analyze patterns of failure and factors predictive of local treatment
      failure in children enrolled on the third Intergroup Rhabdomyosarcoma Study who
      had either biopsy only or subtotal resection of their primary tumor, had no
      distant metastases, and received radiation therapy for local control. PATIENTS
      AND METHODS: Treatment failure was categorized as local, regional nodal, or
      distant metastatic. The 5-year cumulative risk of failure was estimated for each
      category and factors predictive of local failure risk were determined using the
      Cox model and binary recursive partitioning. RESULTS: The estimated 5-year
      cumulative incidence rates by failure category were: total local (with or without
      concurrent regional or distant failure), 19%; total regional nodal, 2%; total
      distant, 11%; and death from toxicity or unknown recurrence type, 4%. Lymph node
      involvement at diagnosis was the single factor most predictive of increased total
      local failure risk (5-year cumulative incidence 32%) compared with children with
      negative nodes or unknown node status (16%). No significant effect on local
      failure risk was observed by total radiotherapy dose over the prescribed range of
      41.4 Gy to 50.4 Gy. For all patients (N = 405), the estimated 5-year failure-free
      survival and overall survival were, respectively, 70% and 78%. CONCLUSION: Local
      failure after radiotherapy for group III rhabdomyosarcoma patients is the
      predominant type of relapse. Involved lymph nodes at diagnosis predict a higher
      risk of local and distant treatment failure compared with patients whose lymph
      nodes are negative.

PMID- 15143084
TI  - Phase I trial of weekly docetaxel with concurrent three-dimensional conformal
      radiation therapy in the treatment of unfavorable localized adenocarcinoma of the
      prostate.
AB  - PURPOSE: A phase I trial was conducted to determine the maximally tolerated dose
      (MTD) of concurrent weekly docetaxel and three-dimensional conformal radiation
      therapy (3-D CRT) in unfavorable localized adenocarcinoma of the prostate.
      PATIENTS AND METHODS: Patients with unfavorable localized adenocarcinoma of the
      prostate underwent daily 3-D CRT to a total dose of 70.2 Gy at 1.8 Gy/fraction
      and concurrent docetaxel given once a week for 8 to 9 weeks. The initial weekly
      docetaxel dose level was 5 mg/m(2) and the docetaxel doses were escalated as
      follows: 8, 12, 16, 20, and 25 mg/m(2). RESULTS: Between January 2000 and August
      2002, 22 men completed the chemoradiation therapy protocol. The dose-limiting
      toxicity was grade 3 diarrhea, which occurred in the first two patients treated
      at the 25 mg/m(2) docetaxel dose level. The MTD of weekly docetaxel was
      determined to be 20 mg/m(2). The overall incidence of grade 2 diarrhea and grade
      2 dysuria was 36% and 23%, respectively. Seven (32%) and 15 (68%) patients did
      not experience any diarrhea or dysuria, respectively. No neutropenia or
      thrombocytopenia was observed. One patient required intermittent urinary
      catheterization 10 months postcompletion of therapy, which resolved without any
      surgical intervention. Seventeen patients remain in prostate-specific antigen
      remission. At a median follow-up interval of 8 months (range, 2 to 27 months),
      all patients are alive. CONCLUSION: Concurrent weekly docetaxel in conjunction
      with 3-D CRT is well tolerated with acceptable toxicity. The MTD of weekly
      docetaxel was determined to be 20 mg/m(2) with concurrent 3-D CRT.

PMID- 15143085
TI  - Effect of dose on immune response in patients vaccinated with an her-2/neu
      intracellular domain protein--based vaccine.
AB  - PURPOSE: To evaluate the safety of an HER-2/neu intracellular domain (ICD)
      protein vaccine and to estimate whether vaccine dose impacts immunogenicity.
      PATIENTS AND METHODS: Twenty-nine patients with HER-2/neu-overexpressing breast
      or ovarian cancer and with no evidence of disease after standard therapy received
      a low- (25 microg), intermediate- (150 microg), or high-dose (900 microg) HER
      2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly
      for 6 months, with granulocyte-macrophage colony-stimulating factor as an
      adjuvant. Toxicity and both cellular and humoral HER-2/neu-specific immunity was
      evaluated. RESULTS: The vaccine was well tolerated. The majority of patients
      (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did
      not predict the magnitude of the T-cell response. The majority of patients (82%)
      also developed HER-2/neu-specific immunoglobulin G antibody immunity. Vaccine
      dose did not predict magnitude or avidity of the HER-2/neu-specific humoral
      immune response. Time to development of detectable HER-2/neu-specific immunity,
      however, was significantly earlier for the high- versus low-dose vaccine group (P
      =.003). Over half the patients retained HER-2/neu-specific T-cell immunity 9 to
      12 months after immunizations had ended. CONCLUSION: The HER-2/neu ICD protein
      vaccine was well tolerated and effective in eliciting HER-2/neu-specific T-cell
      and antibody immunity in the majority of breast and ovarian cancer patients who
      completed the vaccine regimen. Although the dose of vaccine did not impact the
      magnitude of T-cell or antibody immunity elicited, patients receiving the highest
      dose developed HER-2/neu-specific immunity more rapidly than those who received
      the lowest dose.

PMID- 15143086
TI  - The prognostic significance of phosphatidylinositol 3-kinase pathway activation
      in human gliomas.
AB  - PURPOSE: The objectives of this study were to examine activation patterns of the
      phosphatidylinositol 3-kinase (PI3K) pathway in gliomas and to examine the
      prognostic significance of PI3K pathway activation using snap-frozen clinical
      specimens. MATERIALS AND METHODS: Levels of expression of PI3K pathway members
      were assessed in 92 prospectively collected gliomas through quantitative Western
      analysis using total and phospho-specific antibodies for PI3K, Akt, and p70(s6k).
      Both expression and expression levels of these PI3K pathway members were
      correlated with histology, markers of apoptosis (cleaved caspase 3), and with
      clinical outcome (eg, overall survival). RESULTS: It was determined that
      activation of all three PI3K pathway members were significantly more frequent in
      glioblastoma multiforme than in non-glioblastoma multiforme tumors. Levels of
      phospho-PI3K, phospho-Akt, and phospho-p70(s6k) were all found to be inversely
      associated with cleaved caspase 3 levels, suggesting PI3K pathway activation is
      associated with reduced levels of apoptosis. Perhaps most importantly, activation
      of PI3K pathway members was found to be significantly associated with reduced
      survival times when all glioma cases were considered in aggregate. When
      glioblastoma cases were considered separately, the prognostic value of PI3K
      activation remained significant, suggesting that PI3K activation may directly be
      associated with radiation resistance, given that this was the only adjuvant
      therapy administered to this subset of patients. CONCLUSION: Activation of the
      PI3K pathway is significantly associated with increasing tumor grade, decreased
      levels of apoptosis, and with adverse clinical outcome in human gliomas.
      Molecular pathways regulating PI3K activation would appear to be promising
      targets in the clinical management of glioma patients.

PMID- 15143087
TI  - Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in
      patients with recurrent or progressive CNS germ cell tumors.
AB  - PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC)
      followed by autologous stem-cell rescue (ASCR) in patients with relapsed or
      progressive CNS germ cell tumors (GCTs). PATIENTS AND METHODS: Twenty-one
      patients with CNS GCTs who experienced relapse or progression despite having
      received initial chemotherapy and/or radiotherapy were treated with thiotepa
      based HDC regimens followed by ASCR. RESULTS: Estimated overall survival (OS) and
      event-free survival (EFS) rates for the entire group 4 years after HDC were 57%
      +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with
      germinoma survived disease-free after HDC with a median survival of 48 months.
      One patient died as a result of progressive disease (PD) 39 months after HDC, and
      another died as a result of pulmonary fibrosis unrelated to HDC 78 months after
      ASCR without assessable disease. However, only four of 12 patients (33%) with
      nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease,
      with a median survival of 35 months. Eight patients with NGGCTs died as a result
      of PD, with a median survival of 4 months after HDC (range, 2 to 17 months).
      Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for
      OS and EFS, respectively). Patients with complete response to HDC also had
      significantly better outcome (P <.001 for OS and EFS) compared with patients with
      only a partial response or stable disease. There were no toxic deaths because of
      HDC. CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective
      therapy for patients with recurrent CNS germinomas and might be effective in
      patients with recurrent NGGCTs with a low tumor burden.

PMID- 15143088
TI  - Low molecular weight heparin, therapy with dalteparin, and survival in advanced
      cancer: the fragmin advanced malignancy outcome study (FAMOUS).
AB  - PURPOSE: In experimental systems, interference with coagulation can affect tumor
      biology. Furthermore, it has been suggested that low molecular weight heparin
      therapy may prolong survival in patients with cancer. The primary aim of this
      study was to assess survival at 1 year of patients with advanced cancer. PATIENTS
      AND METHODS: Patients with advanced malignancy (N = 385) were randomly assigned
      to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a
      low molecular weight heparin, or placebo for 1 year. RESULTS: The Kaplan-Meier
      survival estimates at 1, 2, and 3 years after randomization for patients
      receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%,
      18%, and 12%, respectively, for patients receiving placebo (P =.19). In an
      analysis not specified a priori, survival was examined in a subgroup of patients
      (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were
      alive 17 months after randomization. In these patients, Kaplan-Meier survival
      estimates at 2 and 3 years from randomization were significantly improved for
      patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%,
      respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4%
      and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7%
      and 2.7%, respectively. CONCLUSION: Dalteparin administration did not
      significantly improve 1-year survival rates in patients with advanced malignancy.
      However, the observed improved survival in a subgroup of patients with a better
      prognosis suggests a potential modifying effect of dalteparin on tumor biology.

PMID- 15143089
TI  - Diagnosis of deep septic thrombophlebitis in cancer patients by fluorine-18
      fluorodeoxyglucose positron emission tomography scanning: a preliminary report.
AB  - PURPOSE: To determine the role of the fluorine-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET) scan in the diagnosis and management of deep septic
      thrombophlebitis (STP). PATIENTS AND METHODS: We conducted a prospective
      observational evaluation of FDG-PET in patients with cancer and suspected STP.
      Retrospective evaluation of patients with cancer and deep venous thrombosis (DVT)
      who underwent FDG-PET and extremity duplex scan (DS) was also performed. RESULTS:
      Strong venous uptake was observed in FDG-PET of nine STP episodes versus 0 of 27
      DVT episodes (P <.001). FDG-PET identified central vein STP in five patients,
      whereas DS and venography were negative in five and two of these patients,
      respectively. FDG-PET diagnosis of STP resulted in therapeutic changes in all
      patients. In four patients, follow-up FDG-PET confirmed resolution. CONCLUSION:
      In cancer patients, FDG-PET identifies STP even in areas not optimally visualized
      by DS or venography, distinguishes STP from DVT, and leads to significant
      therapeutic changes.

PMID- 15143090
TI  - Major depression, adjustment disorders, and post-traumatic stress disorder in
      terminally ill cancer patients: associated and predictive factors.
AB  - PURPOSE: Few studies have been conducted to elucidate the psychological distress
      of terminally ill cancer patients. This study attempted to determine the
      prevalence of adjustment disorders (AD), major depression (MD), and post
      traumatic stress disorder (PTSD) among terminally ill cancer patients, to
      identify factors that contribute to them, and to determine how they change
      longitudinally. PATIENTS AND METHODS: Consecutive terminally ill cancer patients
      were recruited. Patients were assessed for psychiatric disorders by structured
      clinical interview twice: once at the time of their registration with a
      palliative care unit (baseline), and again at the time of their palliative care
      unit admission (follow-up). Possible contributed biomedical and psychosocial
      factors were evaluated. RESULTS: The proportions of patients diagnosed with AD,
      MD, and PTSD at baseline (n = 209) were 16.3%, 6.7%, and 0% respectively, whereas
      at follow-up (n = 85), 10.6% were diagnosed with AD and 11.8% with MD. Lower
      performance status, concern about being a burden to others, and lower
      satisfaction with social support were significantly associated with AD/MD at
      baseline. There were changes in the diagnosis of AD and MD in 30.6% of the
      patients. Only the Hospital Anxiety and Depression Scale at the baseline was
      significantly predictive of AD/MD at follow-up. CONCLUSION: The factors
      underlying psychological distress are multifactorial. Early intervention to treat
      subclinical anxiety and depression may prevent subsequent psychological distress.

PMID- 15143091
TI  - Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer
      pain: a systematic review.
AB  - PURPOSE: To assess the safety and efficacy of nonsteroidal anti-inflammatory
      drugs (NSAIDs), alone or combined with opioids, for the treatment of cancer pain.
      PATIENTS AND METHODS: Forty-two trials involving 3,084 patients met inclusion
      criteria: eight compared NSAID with placebo; 13 compared one NSAID with another;
      23 compared NSAID with opioid, NSAID or opioid versus NSAID plus opioid
      combinations, or NSAID plus opioid combinations versus NSAID plus opioid
      combinations; and nine studies assessed the effect of increasing NSAID dose.
      RESULTS: Sixteen studies lasted 1 week or longer and 11 evaluated a single dose.
      Seven of eight trials demonstrated superior efficacy of single doses of NSAID
      compared with placebo. Only four of 13 studies reported increased efficacy of one
      NSAID compared with another; four other studies found that one NSAID had fewer
      side effects than one or more others. Thirteen of 14 studies found no difference,
      or minimal clinical difference, when comparing an NSAID plus opioid combination
      versus either drug alone. Comparisons between various NSAID plus opioid
      combinations were inconclusive. Four studies demonstrated increased efficacy with
      increased NSAID dose, without dose-dependent increases in side effects.
      CONCLUSION: Heterogeneity of study methods and outcomes precluded meta-analyses.
      Short duration of studies undermines generalization of findings on efficacy and
      safety. On the basis of limited data, NSAIDs appear to be more effective than
      placebo for cancer pain; clear evidence to support superior safety or efficacy of
      one NSAID compared with another is lacking; and trials of combinations of an
      NSAID with an opioid have disclosed either no significant difference, or at most
      a slight but statistically significant advantage, compared with either single
      entity.

PMID- 15143092
TI  - Quality of abstracts describing randomized trials in the proceedings of American
      Society of Clinical Oncology meetings: guidelines for improved reporting.
AB  - PURPOSE: To evaluate the quality of reporting in abstracts describing randomized
      controlled trials (RCTs) included in the Proceedings of American Society of
      Clinical Oncology (ASCO) meetings and to propose reporting guidelines for
      abstracts that are submitted to future meetings. METHODS: Guidelines for
      reporting of RCTs in abstracts were developed by extracting key elements from
      published guidelines for full reports of RCTs, and modified based on an expert
      survey. Abstracts presenting results of RCTs with sample size > or = 200 were
      identified from the ASCO Proceedings for the years 1989 to 1998. Information
      regarding the quality of each abstract was extracted, and a quality score
      (possible range, 0 to 10) was assigned based on adherence to the guidelines.
      RESULTS: Brief description of the intervention, explicit identification of the
      primary end point, and presentation of results accompanied by statistical tests
      were regarded by experts as the most important items to include in an abstract,
      whereas presentation of secondary and subgroup analyses was the least important.
      Deficiencies in reporting were present in almost all of the 510 abstracts; for
      example, only 22% of the abstracts provided explicit identification of the
      primary end point. The median quality score was 5.5 (range, 2.0 to 8.5); the
      quality score improved with time (P <.0001) and was better for oral or plenary
      presentations (P =.0003). CONCLUSION: The quality of reporting of RCTs in
      abstracts submitted to Annual Meetings of ASCO is suboptimal. Although space
      precludes the inclusion of details required in the final report, abstracts could
      be improved through the use of explicit minimal guidelines, which are suggested
      in this article.

PMID- 15143093
TI  - International assessment of the quality of clinical practice guidelines in
      oncology using the Appraisal of Guidelines and Research and Evaluation
      Instrument.
AB  - PURPOSE: To describe the quality of oncology guidelines developed in different
      countries. METHODS: The Appraisal of Guidelines and Research and Evaluation
      (AGREE) Instrument was used to assess the quality of 100 guidelines (including 32
      oncology guidelines) from 13 countries. The criteria of the instrument are
      grouped into six quality domains: scope and purpose, stakeholder involvement,
      rigor of development, clarity and presentation, applicability, and editorial
      independence. RESULTS: Oncology guidelines had significantly higher scores on
      rigor of development than nononcology guidelines (42.2% v 29.4%; P =.02). In
      particular, systematic methods to search for evidence were more often used (P
      =.01); the methods for formulating the recommendations were more clearly
      described (P =.02); and health benefits, risks, and side effects were more often
      considered in formulating the recommendations (P =.03). Although the standardized
      scores for the other domains were not significantly different, the oncology
      guidelines had significantly higher scores for items measuring inclusion of all
      relevant professional groups (P =.05), consideration of patient views (P =.04),
      and presentation of different options (P =.05). Only three organizations
      producing oncology guidelines had standardized scores more than 60% for more than
      three domains. CONCLUSION: The quality of clinical practice guidelines (CPGs) is
      modest in general, but for certain domains, oncology guidelines seem to be of
      better quality than others. The experience of the organization may explain higher
      scores for some items. Research projects and training aimed at improving the
      quality of guidelines should be developed. The AGREE instrument could provide a
      basis for defining steps in a shared development approach to produce high-quality
      CPGs.

PMID- 15143094
TI  - Palliative care inpatient service in a comprehensive cancer center: clinical and
      financial outcomes.
AB  - PURPOSE: Inpatient palliative care units are unavailable in most cancer centers
      and tertiary hospitals. The purpose of this article is to review the outcomes of
      the first 344 admissions to the Palliative Care Inpatient Service (PCIS) at our
      comprehensive cancer center. PATIENTS AND METHODS: We retrospectively reviewed
      our computerized database for clinical and demographic information, length of
      stay, and hospital billing during the first year of the service's operation.
      RESULTS: Three hundred twenty patients were admitted during the study period.
      Their median age was 57 years. The main cancer diagnoses were thoracic or head
      and neck (44%), gastrointestinal (25%), and hematologic malignancy (8%). The main
      referral symptoms were pain (44%), nausea (41%), fatigue (39%), and dyspnea
      (38%). The median length of stay in the PCIS was 7 days (range, 1 to 58 days).
      Fifty-nine patients died while in the PCIS. However, the overall hospital
      mortality rate was not increased compared with that in the year before the
      establishment of the PCIS (3.58% v 3.59%). The mean reimbursement rate for all
      palliative care charges was approximately 57%, and the mean daily charges in the
      PCIS were 38% lower than the mean daily charges for the rest of the hospital.
      Symptom intensity data showed severe distress on admission and significant
      improvement in the main target symptoms. Most patients were discharged to a
      hospice. CONCLUSION: The PCIS has been accepted in our tertiary cancer center on
      the basis of its clinical utility and financial viability.

PMID- 15143095
TI  - Epothilones: mechanism of action and biologic activity.
AB  - Drugs that target microtubules are among the most commonly prescribed anticancer
      therapies. Although the mechanisms by which perturbation of microtubule function
      leads to selective death of cancer cells remain unclear, several new microtubule
      targeting compounds are undergoing clinical testing. In part, these efforts focus
      on overcoming some of the problems associated with taxane-based therapies,
      including formulation and administration difficulties and susceptibility to
      resistance conferred by P-glycoprotein. Epothilones have emerged from these
      efforts as a promising new class of anticancer drugs. Preclinical studies
      indicate that epothilones bind to and stabilize microtubules in a manner similar
      but not identical to that of paclitaxel and that epothilones are effective in
      paclitaxel-resistant tumor models. Clinical phase I and early phase II data are
      available for BMS-247550, BMS-310705, EPO906, and KOS-862. The results suggest
      that these compounds have a broad range of antitumor activity at doses and
      schedules associated with tolerable side effects.

PMID- 15143096
TI  - Soft tissue sarcomas. Case 1. Granulocytic sarcoma: presentation with nodal and
      skin involvement.

PMID- 15143097
TI  - Soft tissue sarcomas. Case 2. Orbital alveolar soft part sarcoma in a child.

PMID- 15143098
TI  - Soft tissue sarcomas. Case 3. Gastrointestinal stromal tumor and Carney's triad.

PMID- 15143099
TI  - Tumor rupture and mitotic index in pediatric sex cord-stromal tumors.

PMID- 15143101
TI  - Pamidronate, hypocalcemia, and calcium and vitamin D supplementation.

PMID- 15143103
TI  - Molecular markers to predict response to gefitinib: EGFR, ErbB-2, or more?

PMID- 15143105
TI  - Socioeconomic differentials in mortality among older people.

PMID- 15143106
TI  - Influential women in occupational health. Linda Rosenstock, MD, MPH--expanding
      collaborations.

PMID- 15143107
TI  - Glossary of terms relating to ethnicity and race: for reflection and debate.
AB  - This glossary focuses on the concepts and terminology used in the study of the
      health of minority ethnic and racial groups. It is hoped that it will stimulate
      debate on this subject so that an internationally applicable glossary may emerge.

PMID- 15143109
TI  - Public health practitioners can learn from the weather forecasters.

PMID- 15143108
TI  - Ethical issues in public health: a qualitative study of public health practice in
      Scotland.
AB  - STUDY OBJECTIVE: To identify ethical issues encountered by staff in the
      development and implementation of public health activities at two sites in
      Scotland. DESIGN: Qualitative research study involving face to face semi
      structured interviews with participants. SETTING: A public health directorate in
      a National Health Service Trust, and a public health demonstration project in
      child health. PARTICIPANTS: Health promotion specialists, managers, nurses,
      public health consultants and specialists, researchers, trainees, and other
      public health staff. MAIN RESULTS: Three main categories of ethical issues were
      identified: paternalism, responsibilities, and ethical decision making.
      Consulting with the community and sharing information raised issues of
      paternalism and honesty. Participants identified multiple and sometimes
      conflicting responsibilities. Barriers to fulfilling responsibilities included
      meeting targets, working with partners, and political influences. Defining the
      limits of responsibilities posed challenges. Participants identified values for
      ideal decision making, but lack of time often led to a more pragmatic approach.
      CONCLUSION: These empirical findings complement and extend existing discussions
      of public health ethics, emphasising the complex nature of ethical issues in
      public health. The implications for public health policy and future research are
      discussed.

PMID- 15143110
TI  - How much downside? Quantifying the relative harm from tobacco taxation.
AB  - OBJECTIVE: To estimate the loss of life expectancy attributable to tobacco
      taxation (via financial hardship and flow-on health effect) in New Zealand.
      DESIGN: Data were used on the gradients in life expectancy and smoking by
      neighbourhood socioeconomic deprivation and survey data on tobacco expenditure.
      Three estimates were modelled of the percentage of the crude association of
      neighbourhood deprivation with life expectancy that might be mediated via
      financial hardship: 100%, 50%, and 25% (best estimate). From this information the
      impact of tobacco taxation on life expectancy was estimated. MAIN RESULTS: For
      the total population, the estimated loss of life expectancy due to tobacco tax
      ranged from 0.005 years to 0.027 years. For people living in the most deprived
      30% of neighbourhoods, the range was 0.009 to 0.044 years (that is, 3 to 16 days
      of lost life expectancy). For the total population the loss of life expectancy
      attributable to tobacco tax ranged from 119 to 460 times less than that
      attributable to deprivation. The loss of life expectancy attributable to tobacco
      tax was 42 to 257 times less than that attributable to smoking. CONCLUSIONS: The
      estimated harm to life expectancy from tobacco taxation (via financial hardship)
      is orders of magnitude smaller than the harm from smoking. Although the analyses
      involve a number of simplistic assumptions, this conclusion is likely to be
      robust. Policy makers should be reassured that tobacco taxation is likely to be
      achieving far more benefit than harm in the general population and in
      socioeconomically deprived populations.

PMID- 15143111
TI  - Evidence based practice in population health: a regional survey to inform
      workforce development and organisational change.
AB  - STUDY OBJECTIVE: To assess current capacity to implement evidence based practice
      (EBP) in population health. DESIGN: Postal survey of a regional population health
      workforce in Sydney, Australia. SETTING: Division of Population Health, South
      Western Sydney Area Health Service. PARTICIPANTS: 104 population health staff
      (response rate: 73%). MAIN RESULTS: In the sample of regional population health
      practitioners, views about the current promotion of EBP were positive. Non
      medical respondents with less that Masters degree were more likely to report
      "high self assessed need" to increase their capacity in EBP (p = 0.022).
      Confidence in understanding of EBP terminology was not associated with seniority
      but with highest level of education reached (p<0.000) and having medical
      qualifications (p<0.000). Occupational category was not associated with
      respondents' self assessed "need for evidence", "need for EBP skills" or "need to
      increase their capacity in EBP" in their current position. The proportion of
      participants "strongly" supporting implementation of a colorectal cancer
      screening programme whose benefit was expressed as relative risk reduction was
      greater than that so supporting a programme whose benefit was expressed as number
      needed to screen (p = 0.008). Most respondents referred to their immediate
      managers when seeking support for EBP. CONCLUSIONS: The findings provide a
      quantitative baseline for capacity building through workplace programmes.
      Managerial commitment has been increased and performance development is now
      underway.

PMID- 15143112
TI  - Epidemic soybean asthma and public health: new control systems and initial
      evaluation in Barcelona, 1996-98.
AB  - OBJECTIVE: To evaluate the new measures adopted to control the risks from soybean
      unloading operations in the Port of Barcelona, after an episode of epidemic
      asthma in June 1996. METHODS: After an initial cautionary suspension of all
      soybean unloading operations, they were subsequently resumed under restrictive
      criteria for time, flux, simultaneity, and meteorological conditions. Emission
      filtration systems based on either micro pore size filters or
      polytetrafluoroethylene membranes on tetratex filters showed promising results.
      RESULTS: Allergen emission underwent a very important decrease to levels 95% to
      98% lower. Emissions from the two plants with unloading operations are in the
      same order of magnitude as the processing plant that does not unload soybean.
      Allergen concentration levels presented fluctuations initially, but the new
      filters decreased mean values; despite increased unloading, allergen levels did
      not increase-mean allergen levels on unloading days (67 U/m(3)) and on days
      without unloading operations (63 U/m(3)) are similar. A panel of patients
      detected a cluster of increased symptoms during unloading operations on a day
      with suboptimal meteorological conditions and comparatively low allergen levels
      (225-415 U/m(3)). Since the June 1996 episode, no further asthma outbreak has
      been detected. CONCLUSIONS: The evaluation shows the effectiveness of the new
      filters in the control of soybean dust emission. With a systematic control
      programme, industrial soybean operations may function near urban centres without
      public health risks. These data may be useful in the development of future
      standards for allergenic agents.

PMID- 15143113
TI  - Estimating physical activity level: the role of domestic activities.

PMID- 15143114
TI  - Socioeconomic inequalities in mortality among elderly people in 11 European
      populations.
AB  - STUDY OBJECTIVE: To describe mortality inequalities related to education and
      housing tenure in 11 European populations and to describe the age pattern of
      relative and absolute socioeconomic inequalities in mortality in the elderly
      European population. DESIGN AND METHODS: Data from mortality registries linked
      with population census data of 11 countries and regions of Europe were acquired
      for the beginning of the 1990s. Indicators of socioeconomic status were
      educational level and housing tenure. The study determined mortality rate ratios,
      relative indices of inequality (RII), and mortality rate differences. The age
      range was 30 to 90+ years. Analyses were performed on the pooled European data,
      including all populations, and on the data of populations separately. Data were
      included from Finland, Norway, Denmark, England and Wales, Belgium, France,
      Austria, Switzerland, Barcelona, Madrid, and Turin. MAIN RESULTS: In Europe
      (populations pooled) relative inequalities in mortality decreased with increasing
      age, but persisted. Absolute educational mortality differences increased until
      the ages 90+. In some of the populations, relative inequalities among older women
      were as large as those among middle aged women. The decline of relative
      educational inequalities was largest in Norway (men and women) and Austria (men).
      Relative educational inequalities did not decrease, or hardly decreased with age
      in England and Wales (men), Belgium, Switzerland, Austria, and Turin (women).
      CONCLUSIONS: Socioeconomic inequalities in mortality among older men and women
      were found to persist in each country, sometimes of similar magnitude as those
      among the middle aged. Mortality inequalities among older populations are an
      important public health problem in Europe.

PMID- 15143115
TI  - Household crowding index: a correlate of socioeconomic status and inter-pregnancy
      spacing in an urban setting.
AB  - OBJECTIVES: This paper examines the effect of household crowding on inter
      pregnancy spacing and its association with socioeconomic indicators, among parous
      mothers delivered in an urban environment. DESIGN: Cross sectional survey.
      METHODS: Sociodemographic data were obtained on 2466 parous women delivering at
      eight hospitals in Greater Beirut over a one year period. Statistical methodology
      comprised Pearson chi(2) test and logistic regression analysis. MAIN RESULTS: A
      significant inverse relation was observed between household crowding and
      socioeconomic status, defined as education and occupation of women and their
      spouses. Inter-pregnancy spacing increased with higher levels of crowding.
      Further analysis suggested that this positive association was confounded by
      maternal demographic characteristics. CONCLUSIONS: These data have shown that
      household crowding, a correlate of low parental socioeconomic status, is
      associated with longer birth intervals. This association, however, seems to be
      largely explained by maternal age and parity.

PMID- 15143116
TI  - Regional variation and time trends in mortality from ischaemic heart disease:
      East and West Germany 10 years after reunification.
AB  - STUDY OBJECTIVE: Within Europe, a pronounced geographical gradient of mortality
      from ischaemic heart disease has been observed with the highest burden in the
      north east and the lowest in the south west. The study objective was to compare
      mortality from ischaemic heart disease between former East and West Germany since
      reunification. DESIGN: Analyses of age standardised mortality rates from
      ischaemic heart disease (ICD-9 410-414, ICD-10 I20-I25) between 1990-1991 and
      2000. SETTING: Former East and West Germany. MAIN RESULTS: After a peak in the
      early 1990s, mortality from ischaemic heart disease has substantially declined in
      both parts of Germany (from 222 to 169 per 100 000 in the East and from 150 to
      116 per 100 000 in the West). The regional difference, however, remained rather
      constant: the rate ratio between the pooled mortality in the East compared with
      the West was 1.51 (95% CI 1.46 to 1.56) in 1991 and 1.45 (95% CI 1.39 to 1.50) in
      2000. These rate ratios were higher in women (1.63 in 1991 and 1.52 in 2000)
      compared with men (1.45 and 1.44, respectively). CONCLUSIONS: Within Germany,
      there has been a pronounced east-west gradient of mortality from ischaemic heart
      disease since reunification. Further insight into possible underlying reasons may
      lead to improved preventive strategies.

PMID- 15143117
TI  - Maternal fish intake in late pregnancy and the frequency of low birth weight and
      intrauterine growth retardation in a cohort of British infants.
AB  - OBJECTIVE: To investigate the relation between maternal fish intake in late
      pregnancy and the frequency of low birth weight and intrauterine growth
      retardation (IUGR). PARTICIPANTS: 11 585 pregnant women in south west England.
      METHODS: Information on fish intake was obtained from a food frequency
      questionnaire sent to the women at 32 weeks' gestation, and used to calculate n-3
      fatty acid (n-3FA) intake from fish. IUGR was defined as a birth weight for
      gestational age and sex below the 10th centile. Confounding variables considered
      included maternal age, height, weight, education, parity, smoking and drinking in
      pregnancy, and whether the mother was living with a partner. Only singleton,
      liveborn infants were included. MAIN RESULTS: Mean daily intakes of fish and n
      3FAs were 32.8 g and 0.147 g respectively. In unadjusted analyses there were
      positive associations between mean birth weight and fish intake or n-3FA intake,
      but these disappeared on adjustment for potential confounders. The frequency of
      IUGR decreased with increasing fish intake-the OR (95%CI) of IUGR in those eating
      no fish was 1.85 (1.44 to 2.38) compared with those in the highest fish intake
      group. On adjustment this relation was attenuated (adjusted OR 1.37 (1.02 to
      1.84)), but the decline in the frequency of IUGR with increasing fish intake
      remained statistically significant. No relation was observed between mean
      gestation and fish or n-3FA intake. CONCLUSIONS: These results lend some support
      to the hypothesis that raising fish or n3-FA intake during pregnancy may increase
      fetal growth rate. However, they provide no evidence that increasing fish
      consumption is associated with an increase in mean gestation.

PMID- 15143118
TI  - Involvement in civil society groups: Is it good for your health?
AB  - STUDY OBJECTIVE: To determine the involvement in civil society groups (CSGs) and
      the impact of this on health. DESIGN: Case study, cross sectional, self
      completion questionnaire, and semi-structured interviews. SETTING: Residents in
      two suburbs in Adelaide, South Australia. PARTICIPANTS: Every household (1038)
      received a questionnaire asking the adult with the next birthday to complete it.
      A total of 530 questionnaires were returned. Sixteen questionnaire respondents
      were also interviewed. MAIN RESULTS: 279 (53%) questionnaire respondents had been
      involved in a CSG in the past 12 months, 190 (36%) in locally based CSGs, and 188
      (35%) in CSGs outside the area. Eleven of the 16 interviewees had been involved
      in a CSG. A path analysis examined the relation between demographic variables,
      CSG involvement, and mental and physical health, as measured by the SF-12.
      Physical health was negatively associated with CSG involvement and older age, and
      positively associated with working full time or part time and higher education
      level. Mental health was positively associated with older age, working full time
      or part time, and higher income but negatively associated with having a child
      under 18, speaking a language other than English and higher education level. Very
      few interviewees made a direct link between CSGs and positive individual health
      outcomes, though some positive community level outcomes were noted. More
      consistent were reports of the detrimental effects of CSG involvement on mental
      and physical health. CONCLUSIONS: Involvement in CSGs was significant but not
      always positive for health. It is possible that CSG involvement is good for a
      community but not necessarily for the individual.

PMID- 15143119
TI  - Employment status, employment conditions, and limiting illness: prospective
      evidence from the British household panel survey 1991-2001.
AB  - OBJECTIVES: To assess the relation of the incidence of, and recovery from,
      limiting illness to employment status, occupational social class, and income over
      time in an initially healthy sample of working age men and women. METHODS: Cox
      proportional hazards models. RESULTS: There were large differences in the risk of
      limiting illness according to occupational social class, with men and women in
      the least favourable employment conditions nearly four times more likely to
      become ill than those in the most favourable. Unemployment and economic
      inactivity also had a powerful effect on illness incidence. Limiting illness was
      not a permanent state for most participants in the study. Employment status was
      also related to recovery. CONCLUSIONS: Having secure employment in favourable
      working conditions greatly reduces the risk of healthy people developing limiting
      illness. Secure employment increases the likelihood of recovery. These findings
      have considerable implications for both health inequality and economic policies.

PMID- 15143121
TI  - Occupational stress and incidence of sick leave in the Belgian workforce: the
      Belstress study.
AB  - CONTEXT: Sick leave is a major problem in public health. The Karasek
      demands/control/social support/strain (JDCS) model has been largely used to
      predict a wide range of health outcomes and to a lesser extent sickness absence.
      STUDY OBJECTIVE: The aim of the study was to test the predictive power of the
      JDCS model in relation with one year incidence of sick leave in a large cohort of
      workers. DESIGN AND SETTING: Cohort study conducted between 1994 and 1998 in 25
      companies across Belgium. PARTICIPANTS: A total of 20 463 workers aged 35 to 59
      years were followed up for sick leave during one year after the baseline survey.
      OUTCOMES: The outcomes were a high sick leave incidence, short spells (>/=7
      days), long spells (>/=28 days), and repetitive spells of sickness absence (>/=3
      spells/year). MAIN RESULTS: Independently from baseline confounding variables, a
      significant association between high strained jobs with low social support and
      repetitive spells of sickness absence was observed in both sexes with odds ratios
      of 1.32 (99% CI, 1.04 to 1.68) in men and 1.61 (99% CI, 1.13 to 2.33) in women.
      In men, high strained jobs with low social support was also significantly
      associated with high sick leave incidence, and short spells of sick leave with
      odds ratios of 1.38 (99% CI, 1.16 to 1.64) and 1.22 (99% CI, 1.05 to 1.44)
      respectively. CONCLUSIONS: Perceived high strain at work especially combined with
      low social support is predictive of sick leave in both sexes of a large cohort of
      the Belgian workforce.

PMID- 15143122
TI  - Type 2 diabetes in grandparents and birth weight in offspring and grandchildren
      in the ALSPAC study.
AB  - OBJECTIVE: To examine the association between a history of type 2 diabetes and
      birth weight of offspring and grandchildren. DESIGN: Prospective observational
      study. Diabetic status, as reported by mothers (F1 generation) was collected on
      grandparents (F0) of babies (F2) born to mothers (F1) who participated in a study
      of maternal and child health. Associations between risk of grandparental diabetes
      and birth weight in mothers (F1) and grandchildren (F2) were analysed using
      linear and logistic regression. SETTING: Avon: comprising of the city of Bristol
      and surrounding areas. PARTICIPANTS: 12 076 singleton babies (F2), their parents
      (F1) and maternal and paternal grandparents (F0). RESULTS: Women (F1) who had no
      parents with type 2 diabetes had lower birth weights than women with one or two
      diabetic parents, after controlling for the age of both parents. There was a U
      shaped association between maternal birth weight and grandmaternal diabetes, but
      no evidence of an association with grandpaternal diabetes. The grandchildren of
      maternal grandparents with type 2 diabetes were more likely to be in the top
      tertile of birth weight than grandchildren of non-diabetics. There was evidence
      for an inverted U shaped association between birth weight of grandchildren and
      diabetes in paternal grandmothers. CONCLUSIONS: This is the first study to show
      intergenerational associations between type 2 diabetes in one generation and
      birth weight in the subsequent two generations. While the study has limitations
      mainly because of missing data, the findings nevertheless provide some support
      for the role of developmental intrauterine effects and genetically determined
      insulin resistance in impaired insulin mediated growth in the fetus.

PMID- 15143125
TI  - Ethnicity and epidemiological research: not so black and white.

PMID- 15143123
TI  - Comparison between the abuse assessment screen and the revised conflict tactics
      scales for measuring physical violence during pregnancy.
AB  - STUDY OBJECTIVE: Because of the promise of its ability to quickly identify cases
      of violence against women during pregnancy, the abuse assessment screen (AAS)
      should be the focus of numerous psychometric evaluations. This paper assesses its
      measurement accuracy compared with the revised conflict tactics scales (CTS2)
      used as standard. DESIGN: Cross sectional study. Besides several ancillary
      questions, the AAS consists of three anchor questions about violence against
      pregnant women. These are inclusive, respectively covering lifetime, preceding 12
      months, and pregnancy periods. These questions are the main focus of this
      article. The CTS2 physical aggression scale consists of 12 items divided into
      minor and severe subscales. A positive event is defined as having at least one
      positive item in the respective subscale. The 12 item score is also used. SETTING
      AND PARTICIPANTS: The instruments were applied to 748 women, 24 to 72 hours after
      delivery in three major public sector maternity wards of Rio de Janeiro from
      March to September 2000. MAIN RESULTS: According to the CTS2, prevalences of
      minor and severe physical violence perpetrated against a pregnant woman are 18.4%
      (95% CI 15.7 to 21.4) and 7.6% (95% CI 5.8 to 9.8), respectively. Taking these
      subscales as standards, sensitivities are 31.9% (95% CI 24.9 to 40.3) and 61.4%
      (95% CI 47.6 to 74.0), respectively. Specificities are above 97%. CONCLUSION:
      These findings are somewhat worrying because the number of victims who are not
      identified and offered assistance is considerable. On a practical note, it would
      be sensible not to use the AAS as a stand alone screening tool until more
      evidence is gathered.

PMID- 15143126
TI  - Siberian live birth sex ratios and the SPrOO hypothesis.

PMID- 15143127
TI  - Spending more, feeling worse: medical care expenditures and self rated health.

PMID- 15143129
TI  - Selective induction of apoptosis by the pyrrolo-1,5-benzoxazepine 7
      [[dimethylcarbamoyl]oxy]-6-(2-naphthyl)pyrrolo-[2,1-d] (1,5)-benzoxazepine (PBOX
      6) in Leukemia cells occurs via the c-Jun NH2-terminal kinase-dependent
      phosphorylation and inactivation of Bcl-2 and Bcl-XL.
AB  - Overexpression of the Bcl-2 proto-oncogene in tumor cells confers resistance
      against chemotherapeutic drugs. In this study, we describe how the novel pyrrolo
      1,5-benzoxazepine compound 7-[[dimethylcarbamoyl]oxy]-6-(2-naphthyl)pyrrolo-[2,1
      d] (1,5)-benzoxazepine (PBOX-6) selectively induces apoptosis in Bcl-2
      overexpressing cancer cells, whereas it shows no cytotoxic effect on normal
      peripheral blood mononuclear cells. PBOX-6 overcomes Bcl-2-mediated resistance to
      apoptosis in chronic myelogenous leukemia (CML) K562 cells by the time- and dose
      dependent phosphorylation and inactivation of antiapoptotic Bcl-2 family members
      Bcl-2 and Bcl-XL. PBOX-6 also induces Bcl-2 phosphorylation and apoptosis in wild
      type T leukemia CEM cells and cells overexpressing Bcl-2. This is in contrast to
      chemotherapeutic agents such as etoposide, actinomycin D, and ultraviolet
      irradiation, whereby overexpression of Bcl-2 confers resistance against
      apoptosis. In addition, PBOX-6 induces Bcl-2 phosphorylation and apoptosis in
      wild-type Jurkat acute lymphoblastic leukemia cells and cells overexpressing Bcl
      2. However, Jurkat cells containing a Bcl-2 triple mutant, whereby the principal
      Bcl-2 phosphorylation sites are mutated to alanine, demonstrate resistance
      against Bcl-2 phosphorylation and apoptosis. PBOX-6 also induces the early and
      transient activation of c-Jun NH2-terminal kinase (JNK) in CEM cells. Inhibition
      of JNK activity prevents Bcl-2 phosphorylation and apoptosis, implicating JNK in
      the upstream signaling pathway leading to Bcl-2 phosphorylation. Collectively,
      these findings identify Bcl-2 phosphorylation and inactivation as a critical step
      in the apoptotic pathway induced by PBOX-6 and highlight its potential as an
      effective antileukemic agent.

PMID- 15143130
TI  - Effect of prolyl endopeptidase on digestive-resistant gliadin peptides in vivo.
AB  - Many gluten peptides elicit proliferative responses from T cells from Celiac
      Sprue patients, influencing the pathogenesis of this small intestinal disorder.
      These peptides are Pro- and Gln-rich in character, suggesting that resistance to
      proteolysis promotes their toxicity. To test this hypothesis, we analyzed the
      digestive resistance of a panel of alpha- and gamma-gliadin peptides believed to
      induce toxicity via diverse mechanisms. Most were highly resistant to gastric and
      pancreatic protease digestion, but they were digested by intestinal brush-border
      peptidases. In some instances, there was accumulation of relatively long
      intermediates. Control peptides from gliadin and myoglobin revealed that
      digestive resistance depended on factors other than size. Prolyl endopeptidase
      (PEP) supplementation substantially reduced the concentrations of these peptides.
      To estimate a pharmacologically useful PEP dose, recombinant PEP was coperfused
      into rat intestine with the highly digestive-resistant 33-mer peptide
      LQLQPF(PQPQLPY)(3) PQPQPF (PEP: peptide weight ratio 1:50 to 1:5). PEP dosing
      experiments indicate significant changes in the average residence time. The in
      vivo benefit of PEP was verified by coperfusion with a mixture of 33-mer and
      partially proteolyzed gliadin. These data verify and extend our earlier proposal
      that gliadin peptides, although resistant to proteolysis, can be processed
      efficiently by PEP supplementation. Indeed, PEP may be able to treat Celiac Sprue
      by reducing or eliminating such peptides from the intestine.

PMID- 15143132
TI  - Dogmas and controversies in the handling of nitrogenous wastes: excretion of
      nitrogenous wastes in human subjects.
AB  - Two major nitrogenous waste products, urea and ammonium (NH(4)(+)), are produced
      in humans when proteins are oxidized, and in this manuscript their excretions are
      examined from two perspectives. First, the specific physiology of each
      nitrogenous waste is reviewed and the current dogmas summarized. Second, their
      excretions are considered in the context of integrative physiology, i.e. the need
      to ensure that the urine composition is appropriate to minimize the risk of
      kidney stone formation. After the latter analysis, weak links in our
      understanding of the overall physiology become apparent and a conundrum is
      defined. The conundrum for the excretion of urea focuses on the fact that urea is
      not an effective osmole in the medullary-collecting duct when vasopressin acts.
      As a result, it appears that urinary urea cannot prevent a large decline in the
      urine flow rate and thereby minimize the risk of forming kidney stones in
      electrolyte-poor urine. The conundrum for the excretion of NH(4)(+) is: high
      rates of NH(4)(+) excretion require a low urine pH, yet a pH approximately 6.0
      must be maintained in order to reduce the risk of precipitating uric acid in the
      urine. Possible ways of resolving these conundrums require novel physiological
      interpretations.

PMID- 15143131
TI  - Dogmas and controversies in the handling of nitrogenous wastes: ammonia tolerance
      in the oriental weatherloach Misgurnus anguillicaudatus.
AB  - The oriental weatherloach Misgurnus anguillicaudatus is an extremely ammonia
      tolerant fish. Many ammonia-protection mechanisms have been reported in this
      fish. Six strategies used by this fish to deal with the problem of excess ammonia
      are described. The fish can (1) reduce ammonia production through reduction in
      protein and/or amino acid catabolism; (2) reduce ammonia production and obtain
      energy through partial amino acid catabolism leading to alanine formation; (3)
      detoxify ammonia to glutamine; (4) tolerate very high ammonia levels in its
      tissues; (5) get rid of ammonia as NH(3) gas and, probably, (6) possesses
      background K(+) channels that are impermeable to NH(4)(+). The effects of
      extracellular ammonia on the contraction performance of the heart from this fish
      were found to be the same as in rainbow trout, an ammonia-sensitive fish. It
      suggests that the hearts of most, if not all, fish species are protected against
      ammonia. MK-801, an NMDA receptor blocker, was found to have a protective effect
      against ammonia intoxication in the oriental weatherloach, which suggests that
      the NMDA receptor, as in mammals, is involved in ammonia toxicity.

PMID- 15143133
TI  - Dogmas and controversies in the handling of nitrogenous wastes: the effect of
      feeding and fasting on the excretion of ammonia, urea and other nitrogenous waste
      products in rainbow trout.
AB  - Ammonia and urea are the primary forms of nitrogen excretion in teleost fish.
      There exists, however, a discrepancy between the sum of ammonia plus urea
      nitrogen and total nitrogen, indicating that 'unknown' nitrogen end products may
      play an important role in nitrogen metabolism. The current study analysed a wide
      range of nitrogen end products in both fed and fasted juvenile rainbow trout.
      Ammonia-N (53-68%) and urea-N (6-10%) were confirmed as the most important forms
      of nitrogenous waste, but an interesting finding was the considerable excretion
      of nitrogen as amino acids (4-10%), via the gills, and as protein (3-11%),
      probably via the body mucus. Use of anal sutures delineated an important role for
      the gastrointestinal tract in the production of ammonia-N and urea-N in fed fish,
      but amino acid-N and protein-N output by this route were both negligible.
      Alternative nitrogen products - trimethylamine, trimethylamine oxide, uric acid,
      and nitrite + nitrate - were not excreted in detectable quantities. Creatine-N
      and creatinine-N outputs were detected but contributed only a small fraction to
      total nitrogen excretion (<1.4%). Despite the wide scope of nitrogenous end
      products investigated, a considerable proportion (12-20%) of nitrogen excretion
      remains unknown. Possible alternative end products and methodological
      considerations are proposed to explain this phenomenon. The findings described
      above were used to recalculate the nitrogen quotient (NQ=(N)/(O(2))) on trout
      that had been either fasted or fed various daily rations (1%, 3% or 5% dry food
      per unit wet body mass per day). Feeding increased oxygen consumption ((O(2)))
      and total-N excretion ((N)). The NQ is often used as a measure of protein
      utilisation in aerobic metabolism and assumes that all protein (and amino acid)
      fuels are converted by oxidation to nitrogenous waste products that are excreted.
      However, the results showed that calculation of the NQ based on total nitrogen
      excretion may overestimate protein utilisation in aerobic metabolism because of
      significant excretion of N in the form of proteins and amino acids, whereas the
      use of summed ammonia-N and urea-N excretion probably underestimates the
      contribution of protein towards aerobic metabolism. These errors increase as
      ration increases, because the discrepancy between total-N excretion and ammonia-N
      + urea-N excretion increases.

PMID- 15143134
TI  - Dogmas and controversies in the handling of nitrogenous wastes: 5-HT2-like
      receptors are involved in triggering pulsatile urea excretion in the gulf
      toadfish, Opsanus beta.
AB  - When injected arterially, serotonin (5-hydroxytryptamine; 5-HT) has been shown to
      elicit naturally sized urea pulse events in the gulf toadfish, Opsanus beta. The
      goal of the present study was to determine which 5-HT receptor(s) was involved in
      mediating this serotonergic stimulation of the pulsatile excretion mechanism.
      Toadfish were surgically implanted with caudal arterial catheters and
      intraperitoneal catheters and injected with either 8-OH-DPAT (1 micro mol kg(
      1)), a selective 5-HT(1A) receptor agonist, alpha-methyl-5-HT (1 micro mol kg(
      1)), a 5-HT(2) receptor agonist, or ketanserin, a 5-HT(2) receptor antagonist
      (0.01, 0.1, 1 and 10 micro mol kg(-1)) plus alpha-methyl-5-HT. 8-OH-DPAT
      injection did not mediate an increase in urea excretion, ruling out the
      involvement of 5-HT(1A) receptors in pulsatile excretion. However, within 5 min,
      alpha-methyl-5-HT injection caused an increase in the excretion of urea in >95%
      (N=27) of the fish injected, with an average pulse size of 652+/-102 micro mol N
      kg(-1) (N=26). With alpha-methyl-5-HT injection there was no corresponding
      increase in ammonia or [(3)H]PEG 4000 permeability. Urea pulses elicited by alpha
      methyl-5-HT were inhibited in a dose-dependent fashion by the 5-HT(2) receptor
      antagonist ketanserin, which at low doses caused a significant inhibition of
      pulse size and at higher doses significantly inhibited the occurrence of
      pulsatile excretion altogether. However, neither 8-OH-DPAT nor alpha-methyl 5-HT
      injection had an effect on plasma cortisol or plasma urea concentrations. These
      findings suggest the involvement of a 5-HT(2)-like receptor in the regulation of
      pulsatile urea excretion.

PMID- 15143135
TI  - Dogmas and controversies in the handling of nitrogenous wastes: ureotely and
      ammonia tolerance in early life stages of the gulf toadfish, Opsanus beta.
AB  - The marine gulf toadfish (Opsanus beta) is an unusual teleost fish as it is able
      to switch between ammoniotelism and ureotelism in response to a variety of
      laboratory conditions. The present study integrates field work conducted in
      Biscayne and Florida Bays, USA with laboratory studies to examine ureotelism
      during the early life history stages of O. beta. Adult toadfish voluntarily
      nested in artificial shelters placed amongst seagrass beds and were found to be
      predominantly ureotelic under natural conditions as the internal shelter water
      had mean urea and ammonia concentrations (N=51) of 14.2+/-1.6 micro mol N l(-1)
      and 8.9+/-0.9 micro mol N l(-1), respectively. Toadfish successfully spawned in
      shelters, providing eggs, larvae and juvenile toadfish for laboratory study. In
      the lab, juvenile toadfish were also ureotelic and urea was excreted in pulsatile
      events that accounted for 62.0+/-5.9% of total urea-N excreted. Excretion rates
      of urea-N and ammonia-N were 1.018+/-0.084 micro mol N h(-1) g(-1) and 0.235+/
      0.095 micro mol N h(-1) g(-1), respectively. Field-collected eggs, larvae and
      juveniles expressed significant levels of the ornithine-urea cycle enzymes
      carbamoyl-phosphate synthetase III, ornithine transcarbamylase and arginase and
      the accessory enzyme glutamine synthetase, all of which increased in activity as
      toadfish developed through early life stages. In juveniles, the ammonia 96-h
      LC(50) value was 875 micro mol N l(-1) and there was a 3-fold increase in
      ornithine transcarbamylase activity in the 1000 micro mol N l(-1) NH(4)Cl
      treatment. The results are discussed in the context of the causal factor(s) for
      ureotelism in toadfish. Furthermore, the results of this study suggest it is
      unlikely that the adaptive significance of ureotelism in toadfish is a means to
      prevent fouling nests with ammonia and in turn poisoning offspring; however,
      additional study is warranted.

PMID- 15143136
TI  - Dogmas and controversies in the handling of nitrogenous wastes: osmoregulation
      during early embryonic development in the marine little skate Raja erinacea;
      response to changes in external salinity.
AB  - Marine elasmobranchs retain relatively high levels of urea to counterbalance the
      osmotic strength of seawater. Oviparous species, such as the little skate Raja
      erinacea, release encapsulated embryos that hatch after about 9 months on the
      seafloor. To study the ureosmotic capability of skate embryos, we measured a
      variety of possible osmolytes and ornithine-urea cycle (OUC) enzyme activities in
      little skate embryos, and determined their physiological response to dilute
      seawater (75% SW) exposure relative to controls (100% SW). The
      urea:trimethylamine oxide (TMAO) + other osmolytes ratio was 2.3-2.7:1. At the
      earliest stage of development investigated (4 months), there were significant
      levels of the key OUC enzyme, carbamoyl phosphate synthetase III, as well as
      ornithine transcarbamoylase, arginase and glutamine synthetase, providing
      evidence for a functional OUC. Embryos (4 and 8 months) survived and recovered
      from exposure to 5 days of 75% SW. There was a significant increase in the rate
      of urea excretion (five- to tenfold), no change in OUC enzyme activities, and
      significant decreases in the tissue content of urea, TMAO and other osmolytes in
      embryos exposed to 75% SW compared to 100% SW. Taken together, the data indicate
      that little skate embryos synthesize and retain urea, as well as a suite of other
      osmolytes, in order to regulate osmotic balance with the external environment.
      Interestingly, these ureosmotic mechanisms are in place as early as 4 months,
      around the time at which the egg capsule opens and the embryo is in more direct
      contact with the external environment.

PMID- 15143137
TI  - Dogmas and controversies in the handling of nitrogenous wastes: expression of
      arginase Type I and II genes in rainbow trout: influence of fasting on liver
      enzyme activity and mRNA levels in juveniles.
AB  - Through analysis of a cDNA library and third-party annotation of available
      database sequences, we characterized the full-length coding regions of rainbow
      trout (Oncorhynchus mykiss) Type I, Onmy-ARG01, and Type II, Onmy-ARG02, arginase
      genes. Two partial related arginase sequences, Onmy-ARG01b and Onmy-ARG02b, and a
      full-length zebrafish arginase coding region (Danio rerio), Dare-ARG02, are also
      reported. Comparison of vertebrate arginase sequences shows that both Type I and
      Type II genes in bony fishes contain a mitochondrial targeting N-terminal domain.
      This suggests that the cytosolic Type I arginase found in ureotelic vertebrates
      arose in the common ancestor of amphibia and mammals. Onmy-ARG01 and Onmy-ARG02
      mRNA was detected in liver, kidney, gill, intestine, red muscle and heart
      tissues. Onmy-ARG01 was expressed at a significantly higher level relative to
      Onmy-ARG02 in liver and red muscle tissue. To investigate whether there was
      differential regulation of Onmy-ARG01 and Onmy-ARG02, juvenile trout were fasted
      for 6 weeks and hepatic enzyme activities and mRNA levels were compared with
      those of fed control fish. There was a 3-fold increase in liver arginase activity
      and a 2-fold increase in Onmy-ARG02 mRNA levels but no change in Onmy-ARG01 mRNA
      levels in fasted fish relative to fed fish. These findings indicate that both
      types of arginase genes are present and expressed in rainbow trout and that the
      pattern of expression varies between tissues. The increase in liver arginase
      activity after a 6-week fast is due, in part, to an increase in the expression of
      Onmy-ARG02 mRNA levels.

PMID- 15143138
TI  - Dogmas and controversies in the handling of nitrogenous wastes: is exogenous
      ammonia a growth stimulant in fish?
AB  - Traditionally, waterborne ammonia is considered a toxicant that decreases
      productivity in aquaculture. However, several recent studies have suggested, but
      not proven, that growth of salmonids might actually be stimulated by chronic
      exposure to very low levels of ammonia. In the present study, two 70-71 day
      growth experiments were conducted under rigorously controlled experimental
      conditions with juvenile rainbow trout at total ammonia concentrations
      ([T(Amm)])=0, 70 and 225 micro mol l(-1), pH 7.6. In the first series, a small
      scale laboratory proof-of-principle study at 15 degrees C, there was a
      significant stimulation of mass gain, gross food conversion efficiency, condition
      factor and protein production per fish at [T(Amm)]=70 micro mol l(-1), without an
      increase in voluntary food consumption or change in 'in-tank' O(2) consumption or
      ammonia excretion rates. These growth stimulatory effects were not seen at
      [T(Amm)]=225 micro mol l(-1), where the fish consumed more food, and excreted
      more ammonia, yet achieved the same mass and protein content as the controls. In
      the second series, a larger study conducted in an aquaculture facility at 6.5
      degrees C, growth rate, conversion efficiency and protein production per fish
      over 71 days were all significantly stimulated at [T(Amm)]=225 micro mol l(-1),
      but not at 70 micro mol l(-1), without any change in voluntary food consumption.
      These effects occurred despite an early inhibition of growth at both [T(Amm)]
      levels. When ration was restricted, growth was reduced and there were no longer
      any differential effects attributable to [T(Amm)]. While the effective levels of
      [T(Amm)] differed between the two series, in both, the P(NH(3)) level stimulating
      growth was approximately 23 micro torr. The results are interpreted as reflecting
      either a stimulation of ammonia incorporation into amino acids and protein
      synthesis and/or a reduction in metabolic costs. The finding that low levels of
      exogenous ammonia can serve as a growth stimulant without altering food
      consumption may be important for aquacultural practice, and challenges
      traditional dogma that the effects of ammonia are detrimental to growth.

PMID- 15143139
TI  - Contributions of different NaPi cotransporter isoforms to dietary regulation of P
      transport in the pyloric caeca and intestine of rainbow trout.
AB  - The anatomical proximity and embryological relationship of the pyloric caeca (PC)
      and small intestine of rainbow trout has led to the frequent assumption, on
      little evidence, that they have the same enzymes and transporters. In trout, the
      PC is an important absorptive organ for dietary nutrients, but its role in
      dietary P absorption has not been reported. We found that apical inorganic
      phosphate (Pi) transport in PC comprises carrier-mediated and diffusive
      components. Carrier-mediated uptake was energy- and temperature-dependent,
      competitively inhibited and Na(+)-independent, and greater than the Na(+)
      dependent intestinal uptake. Pi uptake in PC was pH-sensitive in the presence of
      Na(+). Despite the active Pi transport system in PC, high postprandial luminal Pi
      concentrations ( approximately 20 mmol l(-1)) indicate that diffusive uptake
      represents approximately 92% of total Pi uptake in PC of fed fish. The nucleotide
      sequence of a sodium-phosphate cotransporter (NaPi-II) isoform isolated from PC
      was approximately 8% different from the intestinal NaPi cotransporter. PC-NaPi
      mRNA was abundant in PC but rare in the intestine, whereas intestinal NaPi mRNA
      was abundant in the intestine but scarce in PC. Dietary P restriction reduced
      serum and bone P concentrations, increased intestine-type, but not PC-type, NaPi
      mRNA in PC, and increased Pi uptake in intestine but not in PC. Intestine-type
      NaPi expression may be useful for predicting dietary P deficiency.

PMID- 15143140
TI  - Variation in temperature increases the cost of living in birds.
AB  - The effect of temperature variability on laying birds was studied experimentally,
      using Japanese quail. Two aspects of temperature variability were investigated:
      the effects of regular daily variation in temperature, and of a sudden change in
      temperature. Both of these may become more common as a consequence of climate
      change. These manipulations were carried out at two levels of food supply. Energy
      expenditure increased with higher daily temperature variation, and also after a
      sudden change in temperature, taking several days to settle to a constant level.
      Manipulating daily temperature variation also resulted in smaller eggs being laid
      under more variable temperatures, when food quality was also low. The results
      demonstrate that day-to-day variation in temperature, as well as mean
      temperature, affects energy expenditure, which can have consequences for egg
      production.

PMID- 15143141
TI  - Activation patterns of the tongue-projector muscle during feeding in the imperial
      cave salamander Hydromantes imperialis.
AB  - Salamanders of the genus Hydromantes project their tongues the greatest distance
      of any amphibian to capture prey, up to 80% of body length or approximately 6 cm
      in an adult individual. During tongue projection on distant prey, the tongue is
      shot ballistically and the tongue skeleton leaves the body of the salamander
      entirely. We investigated an aspect of the motor control of this remarkable
      behavior by examining electromyographic patterns within different regions of the
      tongue-projector muscle, the subarcualis rectus (SAR). SAR activation is strongly
      modulated, and features of this modulation can be predicted by tongue-projection
      distance (i.e. prey distance). The strap-like buccal portion of the SAR is always
      activated first and for the longest duration, compared to any other region. It is
      in a position to transmit force generated by the posterior SAR to the floor of
      the mouth, where it originates. The posterior SAR encompasses and applies force
      to the epibranchial of the tongue skeleton, and its activation pattern gradually
      changes from a posterior-to-anterior wave of activation onset during short
      distance projection to an all-at-once pattern during the most extreme long
      distance (ballistic) projection. The duration of activity and EMG area of each
      recorded region of the SAR increase with increasing prey distance, showing
      greater muscle recruitment during long-distance projection. No effect of prey
      capture success was observed in the EMG patterns, indicating that SAR activation
      is controlled in a feed-forward manner.

PMID- 15143143
TI  - The effect of mycoplasmosis on carotenoid plumage coloration in male house
      finches.
AB  - Parasites are widely assumed to cause reduced expression of ornamental plumage
      coloration, but few experimental studies have tested this hypothesis. We captured
      young male house finches Carpodacus mexicanus in Alabama before fall molt and
      randomly divided them into two groups. One group was infected with the bacterial
      pathogen Mycoplasma gallicepticum (MG) and the other group was maintained free of
      MG infection. All birds were maintained through molt on a diet of seeds with
      tangerine juice added to their water as a source of beta-cryptoxanthin, the
      natural precursor to the primary red carotenoid pigment in house finch plumage.
      All males grew drab plumage, but males with MG infection grew feathers that were
      significantly less red (more yellow), less saturated, and less bright than males
      that were not infected. MG targets upper respiratory and ocular tissue. Our
      observations show that a pathogen that does not directly disrupt carotenoid
      absorption or transportation can still have a significant effect on carotenoid
      utilization.

PMID- 15143142
TI  - Sex-dependent effects of gonadal steroids and cortisol on cardiac contractility
      in rainbow trout.
AB  - The purpose of this study was to determine whether steroid hormones modulate
      cardiac function in rainbow trout (Oncorhynchus mykiss Walbaum). We assessed the
      effects of exogenously administered steroids on isolated ventricle strips and
      report that physiological concentrations of androgens, 17beta-estradiol and
      cortisol rapidly (<10 min) enhance inotropism (30-40%) in a sex-specific manner.
      These effects were specific to the hormones studied, absent if animals were
      anesthetized chemically and dependent upon steroid concentration and contraction
      frequency. Based on the use of specific steroid receptor antagonists and key
      enzyme inhibitors, it appears that testosterone, 11-ketotestosterone and cortisol
      each act through specific intracellular receptors in males and that the positive
      inotropism requires the synthesis of polyamines and nitric oxide. Cortisol and
      17beta-estradiol, but not androgens, had similar effects in females and also
      involved similar signaling pathways. Androgen and cortisol effects were additive
      in males but cortisol and 17beta-estradiol were not additive in females,
      suggesting sex differences in the pathways through which these hormones stimulate
      inotropism. In summary, gonadal steroids and cortisol promote ventricular
      contractility in a sex-dependent manner through mechanisms that appear
      multifaceted. Ultimately, steroid-mediated improvements in cardiac performance
      might involve non-genomic pathways and be physiologically important during
      migration, spawning or stressful periods.

PMID- 15143144
TI  - How do cormorants counter buoyancy during submerged swimming?
AB  - Buoyancy is a de-stabilizing force for diving cormorants that forage at shallow
      depths. Having to counter this force increases the cost of transport underwater.
      Cormorants are known to be less buoyant than most water birds but are still
      highly buoyant (rho= approximately 0.8 kg m(-3)) due to their adaptations for
      aerial flight. Nevertheless, cormorants are known to dive at a wide range of
      depths, including shallow dives where buoyancy is maximal. We analyzed the
      kinematics of underwater swimming of the great cormorant (Phalacrocorax carbo
      sinensis) in a shallow pool to discover and evaluate the mechanisms countering
      buoyancy while swimming horizontally. The birds maintained a very uniform cyclic
      paddling pattern. Throughout this cycle, synchronized tilting of the body,
      controlled by the tail, resulted in only slight vertical drifts of the center of
      mass around the average swimming path. We suggest that this tilting behavior
      serves two purposes: (1) the elongated bodies and the long tails of cormorants,
      tilted at a negative angle of attack relative to the swimming direction, generate
      downward directed hydrodynamic lift to resist buoyancy and (2) during the
      propulsive phase, the motion of the feet has a significant vertical component,
      generating a vertical component of thrust downward, which further helps to offset
      buoyancy. The added cost of the drag resulting from this tilting behavior may be
      reduced by the fact that the birds use a burst-and-glide pattern while swimming.

PMID- 15143145
TI  - The effects of surface diameter and incline on the hindlimb kinematics of an
      arboreal lizard (Anolis sagrei).
AB  - Arboreal animals often move in habitats with dense vegetation, narrow perches and
      variable inclines, but effects of arboreal habitat structure on locomotor
      function are poorly understood for most animals. Several species of Anolis
      lizards, which have served as a model group for relating locomotor performance to
      morphology, have decreased maximal sprinting speeds when perch diameter
      decreases. However, the effects of perch diameter on the limb movements of Anolis
      have not been previously studied. Hence, we quantified the hindlimb movements of
      Anolis sagrei, which naturally occurs on a wide variety of perch diameters and
      inclines. We analyzed similar speeds of steady locomotion for combinations of
      flat surfaces and round perches with diameters of 1, 3, 6 and 10 cm and inclines
      of 0 degrees and uphill 45 degrees and 90 degrees. Diameter significantly
      affected more kinematic variables than incline, but many kinematic variables
      changed little with increases in diameter beyond 6 cm. As surface diameter
      increased, the limb posture of A. sagrei became progressively more sprawled.
      Significantly greater knee flexion during stance was important for locating the
      foot more medially during movement on narrow perches. Stride length increased and
      femur depression, femur retraction and long-axis femur rotation decreased
      significantly as the surface diameter increased. The low hip heights on the
      vertical incline and the narrowest perches suggest that bringing the center of
      mass closer to the locomotor surface is important in these circumstances for
      reducing the tendency to topple backwards or sideways. Most of the kinematic
      changes of A. sagrei with decreased perch diameter were opposite those correlated
      with increased speeds of locomotion for terrestrial lizards. The foot was most
      lateral to the hip during the swing phase and maximal lateral displacements
      decreased with decreased perch diameter. Consequently, the width required to
      accommodate limb movement also decreased as perch diameter decreased.

PMID- 15143146
TI  - Arrested development in Xenopus laevis tadpoles: how size constrains
      metamorphosis.
AB  - Xenopus laevis tadpoles that arrest development and remain as larvae for several
      years sometimes occur spontaneously in laboratory populations. These tadpoles
      cease development at an early hindlimb stage, but continue to grow and develop
      into grossly deformed giants. Giant tadpoles lack thyroid glands, and differ in
      morphology and behaviour from normal larvae. They are negatively buoyant,
      typically with small and partially solidified lungs, and have greatly enlarged
      fat bodies. Giant tadpoles have mature gonads with eggs and sperm, whereas normal
      tadpoles of the same stage have undifferentiated gonads. Larval reproduction has
      never been reported in anurans, but gonadal development decoupled from
      metamorphosis brings these giants the closest of any anurans to being truly
      neotenic. We discuss behavioural and morphological factors that may hinder both
      reproduction in giant Xenopus larvae and the evolution of neoteny in anurans in
      general. Experimental treatment with exogenous thyroid hormone induces some, but
      not complete, metamorphic changes in these giants. The limbs and head progress
      through metamorphosis; however, all tadpoles die at the stage when the tail would
      normally be resorbed. The disproportionate growth of tissues and organs in giant
      tadpoles may preclude complete metamorphosis, even under exogenous thyroid
      hormone induction.

PMID- 15143147
TI  - The sea urchin complement homologue, SpC3, functions as an opsonin.
AB  - The purple sea urchin Strongylocentrotus purpuratus expresses a homologue of
      complement component C3 (SpC3), which acts as a humoral opsonin. Significantly
      increased phagocytic activity was evident when yeast target cells were opsonized
      after incubation with coelomic fluid containing SpC3. SpC3 could be detected on
      the surface of yeast, and phagocytic activity could be inhibited by an anti-SpC3
      antibody. This indicates that SpC3 promotes phagocytosis by physically tagging
      target cells for ingestion. Confocal microscopy showed that opsonized yeast were
      phagocytosed by a single coelomocyte type (polygonal phagocytes), presumably
      because these cells express SpC3 receptors. Overall, these data indicate that
      SpC3 is a major humoral opsonin in S. purpuratus coelomic fluid.

PMID- 15143148
TI  - Structural colouration of mammalian skin: convergent evolution of coherently
      scattering dermal collagen arrays.
AB  - For more than a century, the blue structural colours of mammalian skin have been
      hypothesized to be produced by incoherent, Rayleigh or Tyndall scattering. We
      investigated the colour, anatomy, nanostructure and biophysics of structurally
      coloured skin from two species of primates - mandrill (Mandrillus sphinx) and
      vervet monkey (Cercopithecus aethiops) - and two species of marsupials - mouse
      opossum (Marmosa mexicana) and wooly opossum (Caluromys derbianus). We used two
      dimensional (2-D) Fourier analysis of transmission electron micrographs (TEMs) of
      the collagen arrays in the primate tissues to test whether these structural
      colours are produced by incoherent or coherent scattering (i.e. constructive
      interference). The structural colours in Mandrillus rump and facial skin and
      Cercopithecus scrotum are produced by coherent scattering by quasi-ordered arrays
      of parallel dermal collagen fibres. The 2-D Fourier power spectra of the collagen
      arrays from Mandrillus and Cercopithecus reveal ring-shaped distributions of
      Fourier power at intermediate spatial frequencies, demonstrating a substantial
      nanostructure of the appropriate spatial frequency to produce the observed blue
      hues by coherent scattering alone. The Fourier power spectra and the observed
      reflectance spectra falsify assumptions and predictions of the incoherent,
      Rayleigh scattering hypothesis. Samples of blue Marmosa and Caluromys scrotum
      conform generally to the anatomy seen in Mandrillus and Cercopithecus but were
      not sufficiently well preserved to conduct numerical analyses. Colour-producing
      collagen arrays in mammals have evolved multiple times independently within the
      two clades of mammals known to have trichromatic colour vision. Mammalian colour
      producing collagen arrays are anatomically and mechanistically identical to
      structures that have evolved convergently in the dermis of many lineages of
      birds, the tapetum of some mammals and the cornea of some fishes. These collagen
      arrays constitute quasi-ordered 2-D photonic crystals.

PMID- 15143149
TI  - Organic cation transport by Malpighian tubules of Drosophila melanogaster:
      application of two novel electrophysiological methods.
AB  - Transport of the prototypical organic cation tetraethylammonium (TEA) by the
      Malpighian tubules, ureters and gut of Drosophila melanogaster was studied using
      two novel electrophysiological techniques. Both techniques exploited the high
      selectivity of the cation exchanger potassium tetra-p-chlorophenylborate for
      tetraalkylammonium compounds relative to inorganic cations such as K(+). In the
      first technique, TEA fluxes were measured using a non-invasive self-referencing
      TEA-selective microelectrode positioned in the unstirred layer near the surface
      of each tissue. TEA fluxes from bath to lumen as large as 6 pmol cm(-2) s(-1)
      were measured across the lower (reabsorptive) segment of the Malpighian tubule
      and the ureter bathed in saline containing 0.1 mmol l(-1) TEA. Corresponding bath
      to-lumen fluxes across the secretory main segment of the Malpighian tubule and
      the posterior midgut were approximately 1 pmol cm(-2) s(-1). TEA transport by the
      lower Malpighian tubule was enhanced by hyperpolarization of the basolateral
      membrane potential and was inhibited by cimetidine, quinidine, vinblastine and
      verapamil. In the second technique, TEA concentration was measured using a TEA
      selective microelectrode positioned in droplets of fluid secreted by Malpighian
      tubules set up in saline droplets under oil in a Ramsay assay. Results from the
      Ramsay assay confirmed the dominant role of the lower Malpighian tubule in net
      transepithelial secretion of TEA and inhibition of TEA transport by cimetidine.
      Kinetic parameters (J(max) and K(t)) were determined using both approaches.

PMID- 15143151
TI  - Molecular mechanism for the potentiation of the transcriptional activity of human
      liver receptor homolog 1 by steroid receptor coactivator-1.
AB  - The liver receptor homolog 1 (LRH-1) belongs to the Fushi tarazu factor 1 nuclear
      receptor subfamily, and its biological functions are just being unveiled. The
      molecular mechanism for the transcriptional regulation by LRH-1 is not clear yet.
      In this report, we use mutagenesis and reporter gene assays to carry out a
      detailed analysis on the hinge region and the proximal ligand binding domain
      (LBD) of human (h) LRH-1 that possess important regulatory functions. Our results
      indicate that helix 1 of the LBD is essential for the activity of hLRH-1 and that
      the steroid receptor coactivator (SRC)-1 interacts directly with the LBD of hLRH
      1 and significantly potentiates the transcriptional activity of hLRH-1.
      Cotransfection assays demonstrate that overexpressed SRC-1 potentiates hLRH-1
      mediated activation of the cholesterol 7-alpha-hydroxylase promoter and increases
      the transcription of the endogenous cholesterol 7-alpha-hydroxylase in Huh7
      cells. The interaction between SRC-1 and hLRH-1 assumes a unique pattern that
      involves primarily a region containing the glutamine-rich domain of SRC-1, and
      helix 1 and activation function-2 of hLRH-1 LBD. Mutagenesis and molecular
      modeling studies indicate that, similar to mouse LRH-1, the coactivator-binding
      cleft of hLRH-1 LBD is not optimized. An interaction between helix 1 of hLRH-1
      LBD and a region containing the glutamine-rich domain of SRC-1 can provide an
      additional stabilizing force and enhances the recruitment of SRC-1. Similar
      interaction is observed between hLRH-1 and SRC-2/transcriptional intermediary
      factor 2 or SRC-3/acetyltransferase. Moreover, transcriptional intermediary
      factor 2 and acetyltransferase also potentiate the transcriptional activity of
      hLRH-1, suggesting a functional redundancy among SRC family members. These
      findings collectively demonstrate an important functional role of helix 1 in
      cofactor recruitment and reveal a novel molecular mechanism of transcriptional
      regulation and cofactor recruitment mediated by hLRH-1.

PMID- 15143152
TI  - Thyroid hormone positively regulates the enterocyte differentiation marker
      intestinal alkaline phosphatase gene via an atypical response element.
AB  - Thyroid hormone (T3) is a critical regulator of intestinal epithelial development
      and homeostasis, but its mechanism of action within the gut is not well
      understood. We have examined the molecular mechanisms underlying the T3
      activation of the enterocyte differentiation marker intestinal alkaline
      phosphatase (IAP) gene. RT-PCR and Western blotting showed that thyroid hormone
      receptors TRalpha1 and TRbeta1 were expressed in human colorectal adenocarcinoma
      Caco-2 cells. Northern blotting detected expression of two IAP transcripts, which
      were increased approximately 3-fold in response to T3. Transient transfection
      studies with luciferase reporter plasmids carrying various internal and 5'
      deletion mutations of the IAP promoter localized a putative thyroid hormone
      response element (TRE) to a region approximately 620 nucleotides upstream (-620)
      of the ATG start codon. EMSAs using TRalpha1-retinoid X receptor alpha (RXRalpha)
      on sequential 5' and 3' single nucleotide deletions defined the TRE between -632
      and -612 (5'-TTGAACTCAgccTGAGGTTAC-3'). Compared with the consensus TRE, the IAP
      TRE is novel in that it contains an everted repeat of two nonamers (not hexamers)
      separated by three nucleotides. Neither TRalpha1 nor RXRalpha binds to the IAP
      TRE; however, TRbeta1 binds to this TRE with minimal affinity. In the presence of
      TR and RXRalpha, only the TR-RXRalpha heterodimer binds to the IAP-TRE.
      Mutagenesis of either nonamer abolishes the biological activity of IAP promoter.
      We have thus identified a novel response element that appears to mediate the T3
      induced activation of the enterocyte differentiation marker, intestinal alkaline
      phosphatase.

PMID- 15143153
TI  - Inhibition of insulin sensitivity by free fatty acids requires activation of
      multiple serine kinases in 3T3-L1 adipocytes.
AB  - Insulin receptor substrate (IRS) has been suggested as a molecular target of free
      fatty acids (FFAs) for insulin resistance. However, the signaling pathways by
      which FFAs lead to the inhibition of IRS function remain to be established. In
      this study, we explored the FFA-signaling pathway that contributes to serine
      phosphorylation and degradation of IRS-1 in adipocytes and in dietary obese mice.
      Linoleic acid, an FFA used in this study, resulted in a reduction in insulin
      induced glucose uptake in 3T3-L1 adipocytes. This mimics insulin resistance
      induced by high-fat diet in C57BL/6J mice. The reduction in glucose uptake is
      associated with a decrease in IRS-1, but not IRS-2 or GLUT4 protein abundance.
      Decrease in IRS-1 protein was proceeded by IRS-1 (serine 307) phosphorylation
      that was catalyzed by serine kinases inhibitor kappaB kinase (IKK) and c-JUN NH2
      terminal kinase (JNK). IKK and JNK were activated by linoleic acid and inhibition
      of the two kinases led to prevention of IRS-1 reduction. We demonstrate that
      protein kinase C (PKC) theta is expressed in adipocytes. In 3T3-L1 adipocytes and
      fat tissue, PKCtheta was activated by fatty acids as indicated by its
      phosphorylation status, and by its protein level, respectively. Activation of
      PKCtheta contributes to IKK and JNK activation as inhibition of PKCtheta by
      calphostin C blocked activation of the latter kinases. Inhibition of either
      PKCtheta or IKK plus JNK by chemical inhibitors resulted in protection of IRS-1
      function and insulin sensitivity in 3T3-L1 adipocytes. These data suggest that:
      1) activation of PKCtheta contributes to IKK and JNK activation by FFAs; 2) IKK
      and JNK mediate PKCtheta signals for IRS-1 serine phosphorylation and
      degradation; and 3) this molecular mechanism may be responsible for insulin
      resistance associated with hyperlipidemia.

PMID- 15143154
TI  - Differential pathways of angiotensin II-induced extracellularly regulated kinase
      1/2 phosphorylation in specific cell types: role of heparin-binding epidermal
      growth factor.
AB  - Stimulation of the angiotensin II (Ang II) type 1 receptor (AT1-R) causes
      phosphorylation of extracellularly regulated kinases 1 and 2 (ERK1/2) via
      epidermal growth factor receptor (EGF-R) transactivation-dependent or 
      independent pathways in Ang II target cells. Here we examined the mechanisms
      involved in agonist-induced EGF-R transactivation and subsequent ERK1/2
      phosphorylation in clone 9 (C9) hepatocytes, which express endogenous AT1-R, and
      COS-7 and human embryonic kidney (HEK) 293 cells transfected with the AT1-R. Ang
      II-induced ERK1/2 activation was attenuated by inhibition of Src kinase and of
      matrix metalloproteinases (MMPs) in C9 and COS-7 cells, but not in HEK 293 cells.
      Agonist-mediated MMP activation in C9 cells led to shedding of heparin-binding
      EGF (HB-EGF) and stimulation of ERK1/2 phosphorylation. Blockade of HB-EGF action
      by neutralizing antibody or its selective inhibitor, CRM197, attenuated ERK1/2
      activation by Ang II. Consistent with its agonist action, HB-EGF stimulation of
      these cells caused marked phosphorylation of the EGF-R and its adapter molecule,
      Shc, as well as ERK1/2 and its dependent protein, p90 ribosomal S6 kinase, in a
      manner similar to that elicited by Ang II or EGF. Although the Tyr319 residue of
      the AT1-R has been proposed to be an essential regulator of EGF-R
      transactivation, stimulation of wild-type and mutant (Y319F) AT1-R expressed in
      COS-7 cells caused EGF-R transactivation and subsequent ERK1/2 phosphorylation
      through release of HB-EGF in a Src-dependent manner. In contrast, the
      noninvolvement of MMPs in HEK 293 cells, which may reflect the absence of Src
      activation by Ang II, was associated with lack of transactivation of the EGF-R.
      These data demonstrate that the individual actions of Ang II on EGF-R
      transactivation in specific cell types are related to differential involvement of
      MMP-dependent HB-EGF release.

PMID- 15143155
TI  - 17beta-Estradiol inhibits class II major histocompatibility complex (MHC)
      expression: influence on histone modifications and cbp recruitment to the class
      II MHC promoter.
AB  - Major histocompatibility complex (MHC) class II proteins are important for the
      initiation of immune responses and are essential for specific recognition of
      foreign antigens by the immune system. Regulation of class II MHC expression
      primarily occurs at the transcriptional level. The class II transactivator
      protein is the master regulator that is essential for both constitutive and
      interferon-gamma-inducible class II MHC expression. Estrogen [17beta-estradiol
      (17beta-E2)] has been shown to have immunomodulatory effects. In this study, we
      show that 17beta-E2 down-regulates interferon-gamma inducible class II MHC
      protein levels on brain endothelial cells, as well as other cell types
      (astrocytes, fibrosacroma cells, macrophages). The inhibitory effects of 17beta
      E2 on class II MHC expression are not due to changes in class II transactivator
      mRNA or protein levels, rather, 17beta-E2 mediates inhibition at the level of
      class II MHC gene expression. We demonstrate that 17beta-E2 attenuates H3 and H4
      histone acetylation and cAMP response element binding protein-binding protein
      association with the class II MHC promoter, suggesting that 17beta-E2 inhibits
      class II MHC expression by a novel mechanism involving modification of the
      histone acetylation status of the class II MHC promoter.

PMID- 15143156
TI  - Polyanions and the proteome.
AB  - The behavior of the proteome reflects spatial and temporal organization both
      within and without cells. We propose that various macromolecular entities
      possessing polyanionic character such as proteoglycans, lipid bilayer surfaces,
      microtubules, microfilaments, and polynucleotides may provide a functional
      network that mediates a variety of cellular phenomena. The interaction of
      proteins with this array of polyanions is characterized by a lower degree of
      specificity than seen with most commonly recognized macromolecular interactions.
      In this commentary, potential roles for this polyanion network in diverse
      functions such as protein/protein interactions, protein folding and
      stabilization, macromolecular transport, and various disease processes are all
      considered, as well as the use of polyanions as therapeutic agents. The role of
      small polyanions in the regulation of protein/polyanion interactions is also
      postulated. We provide preliminary experimental analysis of the extent to which
      proteins interact with polyanions inside cells using a combination of two
      dimensional chromatographic and electrophoretic methods and antibody arrays. We
      conclude that many hundreds to thousands of such interactions are present in
      cells and argue that future understanding of the proteome will require that the
      "polyanion world" be taken into account.

PMID- 15143157
TI  - Molecular and cellular determinants of estrogen receptor alpha expression.

PMID- 15143158
TI  - Mitochondrial AKAP121 binds and targets protein tyrosine phosphatase D1, a novel
      positive regulator of src signaling.
AB  - A-kinase anchor protein 121 (AKAP121) and its spliced isoform AKAP84 anchor
      protein kinase A (PKA) to the outer membrane of mitochondria, focusing and
      enhancing cyclic AMP signal transduction to the organelle. We find that
      AKAP121/84 also binds PTPD1, a src-associated protein tyrosine phosphatase. A
      signaling complex containing AKAP121, PKA, PTPD1, and src is assembled in vivo.
      PTPD1 activates src tyrosine kinase and increases the magnitude and duration of
      epidermal growth factor (EGF) signaling. EGF receptor phosphorylation and
      downstream activation of ERK 1/2 and Elk1-dependent gene transcription are
      enhanced by PTPD1. Expression of a PTPD1 mutant lacking catalytic activity
      inhibits src and downregulates ERK 1/2 but does not affect the activity of c-Jun
      N-terminal kinase 1/2 and p38alpha mitogen-activated protein kinase. AKAP121
      binds to and redistributes PTPD1 from the cytoplasm to mitochondria and inhibits
      EGF signaling. Our findings indicate that PTPD1 is a novel positive regulator of
      src signaling and a key component of the EGF transduction pathway. By binding
      and/or targeting the phosphatase on mitochondria, AKAP121 modulates the amplitude
      and persistence of src-dependent EGF transduction pathway. This represents the
      first example of physical and functional interaction between AKAPs and a protein
      tyrosine phosphatase.

PMID- 15143159
TI  - Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum
      formation in the embryonic heart.
AB  - Molecular mechanisms for the dorso-ventral patterning and interventricular septum
      formation in the embryonic heart are unknown. To investigate a role of
      Hand1/eHAND in cardiac chamber formation, we generated Hand1/eHAND knock-in mice
      where Hand1/eHAND cDNA was placed under the control of the MLC2V promoter. In
      Hand1/eHAND knock-in mice, the outer curvature of the right and left ventricles
      expanded more markedly. Moreover, there was no interventricular groove or septum
      formation, although molecularly, Hand1/eHAND knock-in hearts had two ventricles.
      However, the morphology of the inner curvature of the ventricles, the
      atrioventricular canal, and the outflow tract was not affected by Hand1/eHAND
      expression. Furthermore, expression of Hand1/eHAND in the whole ventricles
      altered the expression patterns of Chisel, ANF, and Hand2/dHAND but did not
      affect Tbx5 expression. In contrast, the interventricular septum formed normally
      in transgenic embryos overexpressing Hand1/eHAND in the right ventricle but not
      in the boundary region. These results suggested that Hand1/eHAND is involved in
      expansion of the ventricular walls and that absence of Hand1/eHAND expression in
      the boundary region between the right and left ventricles may be critical in the
      proper formation of the interventricular groove and septum. Furthermore,
      Hand1/eHAND is not a master regulatory gene that specifies the left ventricle
      myocyte lineage but may control the dorso-ventral patterning in concert with
      additional genes.

PMID- 15143160
TI  - Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block
      polymerization and transformation activity.
AB  - The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in
      human malignancies, resulting in the formation of oncogenic ETV6 gene fusions.
      Many of the known partner genes encode protein tyrosine kinases (PTKs),
      generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN),
      comprised of the ETV6 SAM domain fused to the NTRK3 PTK, is unique among ETV6
      chimeric oncoproteins, as it is expressed in cancers of multiple lineages. We
      initially hypothesized that, similar to other ETV6-PTK chimeras, SAM-mediated
      dimerization of EN leads to constitutive activation of the PTK and downstream
      signaling cascades. However, when the EN SAM domain was replaced with an
      inducible FK506 binding protein (FKBP) dimerization system, resulting FKBP-NTRK3
      chimeras failed to transform NIH 3T3 cells even though PTK activation was
      preserved. It was recently shown that the ETV6 SAM domain has two potential
      interacting surfaces, raising the possibility that this domain can mediate
      protein polymerization. We therefore mutated each EN SAM binding interface in a
      manner shown previously to abolish self-association of wild-type ETV6. Each
      mutation completely blocked the ability of EN to polymerize, to activate its PTK,
      and to transform NIH 3T3 cells. Furthermore, EN itself formed large polymeric
      structures within cells while mutant EN proteins were present only as monomers.
      Finally, we observed a dominant negative effect on the transformation of isolated
      SAM domains coexpressed in EN-transformed cells. Taken together, our results
      suggest that higher-order polymerization may be a critical requirement for the
      transformation activity of EN and possibly other ETV6-PTK fusion proteins.

PMID- 15143161
TI  - Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling
      enzymes during adipogenic induction of the peroxisome proliferator-activated
      receptor gamma nuclear hormone receptor.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) regulates
      adipogenesis, lipid metabolism, and glucose homeostasis, and roles have emerged
      for this receptor in the pathogenesis and treatment of diabetes, atherosclerosis,
      and cancer. We report here that induction of the PPARgamma activator and
      adipogenesis forced by overexpression of adipogenic regulatory proteins is
      blocked upon expression of dominant-negative BRG1 or hBRM, the ATPase subunits of
      distinct SWI/SNF chromatin-remodeling enzymes. We demonstrate that histone
      hyperacetylation and the binding of C/EBP activators, polymerase II (Pol II), and
      general transcription factors (GTFs) initially occurred at the inducible
      PPARgamma2 promoter in the absence of SWI/SNF function. However, the polymerase
      and GTFs were subsequently lost from the promoter in cells expressing dominant
      negative SWI/SNF, explaining the inhibition of PPARgamma2 expression. To
      corroborate these data, we analyzed interactions at the PPARgamma2 promoter in
      differentiating preadipocytes. Changes in promoter structure, histone
      hyperacetylation, and binding of C/EBP activators, Pol II, and most GTFs preceded
      the interaction of SWI/SNF enzymes with the PPARgamma2 promoter. However,
      transcription of the PPARgamma2 gene occurred only upon subsequent association of
      SWI/SNF and TFIIH with the promoter. Thus, induction of the PPARgamma nuclear
      hormone receptor during adipogenesis requires SWI/SNF enzymes to facilitate
      preinitiation complex function.

PMID- 15143162
TI  - Rap2B-dependent stimulation of phospholipase C-epsilon by epidermal growth factor
      receptor mediated by c-Src phosphorylation of RasGRP3.
AB  - Receptor tyrosine kinase regulation of phospholipase C-epsilon (PLC-epsilon),
      which is under the control of Ras-like and Rho GTPases, was studied with HEK-293
      cells endogenously expressing PLC-coupled epidermal growth factor (EGF)
      receptors. PLC and Ca(2+) signaling by the EGF receptor, which activated both PLC
      gamma1 and PLC-epsilon, was specifically suppressed by inactivation of Ras
      related GTPases with clostridial toxins and expression of dominant-negative
      Rap2B. EGF induced rapid and sustained GTP loading of Rap2B, binding of Rap2B to
      PLC-epsilon, and Rap2B-dependent translocation of PLC-epsilon to the plasma
      membrane. GTP loading of Rap2B by EGF was inhibited by chelation of intracellular
      Ca(2+) and expression of lipase-inactive PLC-gamma1 but not of PLC-epsilon.
      Expression of RasGRP3, a Ca(2+)/diacylglycerol-regulated guanine nucleotide
      exchange factor for Ras-like GTPases, but not expression of various other
      exchange factors enhanced GTP loading of Rap2B and PLC/Ca(2+) signaling by the
      EGF receptor. EGF induced tyrosine phosphorylation of RasGRP3, but not RasGRP1,
      apparently caused by c-Src; inhibition of c-Src interfered with EGF-induced Rap2B
      activation and PLC stimulation. Collectively, these data suggest that the EGF
      receptor triggers activation of Rap2B via PLC-gamma1 activation and tyrosine
      phosphorylation of RasGRP3 by c-Src, finally resulting in stimulation of PLC
      epsilon.

PMID- 15143163
TI  - The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd.
AB  - The mechanism by which the high-bone-mass (HBM) mutation (G171V) of the Wnt
      coreceptor LRP5 regulates canonical Wnt signaling was investigated. The mutation
      was previously shown to reduce DKK1-mediated antagonism, suggesting that the
      first YWTD repeat domain where G171 is located may be responsible for DKK
      mediated antagonism. However, we found that the third YWTD repeat, but not the
      first repeat domain, is required for DKK1-mediated antagonism. Instead, we found
      that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperone
      protein for LRP5/6 that is required for transport of the coreceptors to cell
      surfaces, resulting in fewer LRP5 molecules on the cell surface. Although the
      reduction in the number of cell surface LRP5 molecules led to a reduction in Wnt
      signaling in a paracrine paradigm, the mutation did not appear to affect the
      activity of coexpressed Wnt in an autocrine paradigm. Together with the
      observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and
      that osteocytes produce paracrine DKK1, we think that the G171V mutation may
      cause an increase in Wnt activity in osteoblasts by reducing the number of
      targets for paracrine DKK1 to antagonize without affecting the activity of
      autocrine Wnt.

PMID- 15143164
TI  - A direct binding site for Grb2 contributes to transformation and leukemogenesis
      by the Tel-Abl (ETV6-Abl) tyrosine kinase.
AB  - A direct binding site for the Grb2 adapter protein is required for the induction
      of fatal chronic myeloid leukemia (CML)-like disease in mice by Bcr-Abl. Here, we
      demonstrate direct binding of Grb2 to the Tel-Abl (ETV6-Abl) fusion protein, the
      product of complex (9;12) chromosomal translocations in human leukemia, via
      tyrosine 314 encoded by TEL exon 5. A Tel-Abl point mutant (Y314F) and a splice
      variant without TEL exon 5 sequences (Deltae5) lacked Grb2 interaction and
      exhibited decreased binding and phosphorylation of the scaffolding protein Gab2
      and impaired activation of phosphatidylinositol 3-kinase, Akt, and extracellular
      signal-regulated kinase/mitogen-activated protein kinase in hematopoietic cells.
      Tel-Abl Y314F and Deltae5 were unable to transform fibroblasts to anchorage
      independent growth and were defective for B-lymphoid transformation in vitro and
      lymphoid leukemogenesis in vivo. Previously, we demonstrated that full-length Tel
      Abl induced two distinct myeloproliferative diseases in mice: CML-like leukemia
      similar to that induced by Bcr-Abl and a novel syndrome of small-bowel myeloid
      infiltration endotoxemia and hepatic and renal failure. Lack of the Grb2 binding
      site had no effect on development of small bowel syndrome but significantly
      attenuated the induction of CML-like disease by Tel-Abl. These results suggest
      that direct binding of Grb2 is a common mechanism contributing to leukemogenesis
      by oncogenic Abl fusion proteins.

PMID- 15143165
TI  - An extracellular signal-regulated kinase 1- and 2-dependent program of chromatin
      trafficking of c-Fos and Fra-1 is required for cyclin D1 expression during cell
      cycle reentry.
AB  - Mitogens activate cell signaling and gene expression cascades that culminate in
      expression of cyclin D1 during the G(0)-to-G(1) transition of the cell cycle.
      Using cell cycle arrest in response to oxidative stress, we have delineated a
      dynamic program of chromatin trafficking of c-Fos and Fra-1 required for cyclin
      D1 expression during cell cycle reentry. In serum-stimulated lung epithelial
      cells, c-Fos was expressed, recruited to chromatin, phosphorylated at
      extracellular signal-regulated kinase 1- and 2 (ERK1,2)-dependent sites, and
      degraded prior to prolonged recruitment of Fra-1 to chromatin. Immunostaining
      showed that expression of nuclear c-Fos and that of cyclin D1 are mutually
      exclusive, whereas nuclear Fra-1 and cyclin D1 are coexpressed as cells traverse
      G(1). Oxidative stress prolonged the accumulation of phospho-ERK1,2 and phospho-c
      Fos on chromatin, inhibited entry of Fra-1 into the nucleus, and blocked cyclin
      D1 expression. After induction of the immediate-early gene response in the
      presence of oxidative stress, inhibition of ERK1,2 signaling promoted degradation
      of c-Fos, recruitment of Fra-1 to chromatin, and expression of cyclin D1. Our
      data indicate that termination of nuclear ERK1,2 signaling is required for an
      exchange of Fra-1 for c-Fos on chromatin and initiation of cyclin D1 expression
      at the G(0)-to-G(1) transition of the cell cycle.

PMID- 15143166
TI  - Physical and functional interaction between the Bloom's syndrome gene product and
      the largest subunit of chromatin assembly factor 1.
AB  - Bloom's syndrome (BS) is a genomic instability disorder characterized by cancer
      susceptibility. The protein defective in BS, BLM, belongs to the RecQ family of
      DNA helicases. In this study, we found that BLM interacts with hp150, the largest
      subunit of chromatin assembly factor 1 (CAF-1), in vitro and in vivo.
      Colocalization of a proportion of the cellular complement of these two proteins
      is found at specific nuclear foci coinciding with sites of DNA synthesis in the S
      phase. This colocalization increases in the presence of agents that damage DNA or
      inhibit DNA replication. In support of a functional interaction between BLM and
      CAF-1, we show that BLM inhibits CAF-1-mediated chromatin assembly during DNA
      repair in vitro. Although CAF-1 activity is not altered in BLM-deficient cells,
      the absence of BLM does impair the ability of CAF-1 to be mobilized within the
      nucleus in response to hydroxyurea treatment. Our results provide the first link
      between BLM and chromatin assembly coupled to DNA repair and suggest that BLM and
      CAF-1 function in a coordinated way to promote survival in response to DNA damage
      and/or replication blockade.

PMID- 15143167
TI  - Disruption of CCTbeta2 expression leads to gonadal dysfunction.
AB  - There are two mammalian genes that encode isoforms of CTP:phosphocholine
      cytidylyltransferase (CCT), a key rate-controlling step in membrane phospholipid
      biogenesis. Quantitative determination of the CCT transcripts reveals that
      CCTalpha is ubiquitously expressed and is found at the highest levels in the
      testis and lung, with lower levels in the liver and ovary. CCTbeta2 is a very
      minor isoform in most tissues but is significantly expressed in the brain, lung,
      and gonads. CCTbeta3 is the third isoform recently discovered in mice and is
      expressed in the same tissues as CCTbeta2, with its highest level in testes. We
      investigated the role(s) of CCTbeta2 by generating knockout mice. The brains and
      lungs of mice lacking CCTbeta2 expression did not exhibit any overt defects. On
      the other hand, a large percentage of the CCTbeta2(-/-) females were sterile and
      their ovaries exhibited defective ovarian follicle development. The proportion of
      female CCTbeta2(-/-) mice with defective ovaries increased as the animals aged.
      The rare litters born from CCTbeta2(-/-) x CCTbeta2(-/0) matings had the normal
      number of pups. The abnormal ovarian histopathology was characterized by
      disorganization of the tissue in young adult mice and absence of follicles and
      ova in older mice, along with interstitial stromal cell hyperplasia which
      culminated in the emergence of tubulostromal ovarian tumors by 16 months of age.
      Grossly defective CCTbeta2(-/-) ovaries were associated with high follicle
      stimulating (FSH) and luteinizing (LH) hormone levels. Male CCTbeta2(-/0) mice
      exhibited progressive multifocal testicular degeneration and reduced fertility
      but had normal FSH and LH levels. Thus, the most notable phenotype of CCTbeta2
      knockout mice was gonad degeneration and reproductive deficiency. The results
      indicate that although CCTbeta2 is expressed at very low levels compared to the
      alpha-isoform, loss of CCTbeta2 expression causes a breakdown in the gonadal
      response to hormonal stimulation.

PMID- 15143168
TI  - Bromodomain factor 1 (Bdf1) is phosphorylated by protein kinase CK2.
AB  - Bromodomain factor 1 (Bdf1) associates with Saccharomyces cerevisiae TFIID and
      corresponds to the C-terminal half of higher eukaryotic TAF1. It also associates
      with the SWR-C complex, which is important for Htz1 deposition. Bdf1 binds
      preferentially to acetylated histone H4. Bdf1 is phosphorylated, but the
      mechanism and significance of this modification have been unclear. Two distinct
      regions within Bdf1 are phosphorylated; one is just C terminal to the
      bromodomains and the other is near the C terminus. Mutational analysis shows that
      phosphorylation is necessary for Bdf1 function in vivo. Endogenous protein kinase
      CK2 purifies with Bdf1 and phosphorylates both domains. A similar mechanism may
      be responsible for phosphorylation of the C-terminal region of mammalian TAF1.
      These findings suggest that CK2 phosphorylation of Bdf1 may regulate RNA
      polymerase II transcription and/or chromatin structure.

PMID- 15143169
TI  - Glucocorticoids and tumor necrosis factor alpha cooperatively regulate toll-like
      receptor 2 gene expression.
AB  - Tumor necrosis factor alpha (TNF-alpha) and glucocorticoids are widely recognized
      as mutually antagonistic regulators of adaptive immunity and inflammation.
      Surprisingly, we show here that they cooperatively regulate components of innate
      immunity. The Toll-like receptor 2 (TLR2) gene encodes a transmembrane receptor
      critical for triggering innate immunity. Although TLR2 mRNA and protein are
      induced by inflammatory molecules such as TNF-alpha, we show that TLR2 is also
      induced by the anti-inflammatory glucocorticoids in cells where they also
      regulate MKP-1 mRNA and protein levels. TNF-alpha and glucocorticoids cooperate
      to regulate the TLR2 promoter, through the involvement of a 3' NF-kappaB site, a
      STAT-binding element, and a 3' glucocorticoid response element (GRE). Molecular
      studies show that the IkappaBalpha superrepressor or a STAT dominant negative
      element prevented TNF-alpha and dexamethasone stimulation of TLR2 promoter.
      Similarly, an AF-1 deletion mutant of glucocorticoid receptor or ablation of a
      putative GRE notably reduced the cooperative regulation of TLR2. Using chromatin
      immunoprecipitation assays, we demonstrate that all three transcription factors
      interact with both endogenous and transfected TLR2 promoters after stimulation by
      TNF-alpha and dexamethasone. Together, these studies define novel signaling
      mechanism for these three transcription factors, with a profound impact on
      discrimination of innate and adaptive immune responses.

PMID- 15143170
TI  - Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent
      mechanism, irrespective of their ability to stabilize beta-catenin.
AB  - Wnt glycoproteins play essential roles in the development of metazoan organisms.
      Many Wnt proteins, such as Wnt1, activate the well-conserved canonical Wnt
      signaling pathway, which results in accumulation of beta-catenin in the cytosol
      and nucleus. Other Wnts, such as Wnt5a, activate signaling mechanisms which do
      not involve beta-catenin and are less well characterized. Dishevelled (Dvl) is a
      key component of Wnt/beta-catenin signaling and becomes phosphorylated upon
      activation of this pathway. In addition to Wnt1, we show that several Wnt
      proteins, including Wnt5a, trigger phosphorylation of mammalian Dvl proteins and
      that this occurs within 20 to 30 min. Unlike the effects of Wnt1, phosphorylation
      of Dvl in response to Wnt5a is not concomitant with beta-catenin stabilization,
      indicating that Dvl phosphorylation is not sufficient to activate canonical
      Wnt/beta-catenin signaling. Moreover, neither Dickkopf1, which inhibits Wnt/beta
      catenin signaling by binding the Wnt coreceptors LRP5 and -6, nor dominant
      negative LRP5/6 constructs could block Wnt-mediated Dvl phosphorylation. We
      conclude that Wnt-induced phosphorylation of Dvl is independent of LRP5/6
      receptors and that canonical Wnts can elicit both LRP-dependent (to beta-catenin)
      and LRP-independent (to Dvl) signals. Our data also present Dvl phosphorylation
      as a general biochemical assay for Wnt protein function, including those Wnts
      that do not activate the Wnt/beta-catenin pathway.

PMID- 15143172
TI  - Promoter-dependent mechanism leading to selective hypomethylation within the 5'
      region of gene MAGE-A1 in tumor cells.
AB  - Several male germ line-specific genes, including MAGE-A1, rely on DNA methylation
      for their repression in normal somatic tissues. These genes become activated in
      many types of tumors in the course of the genome-wide demethylation process which
      often accompanies tumorigenesis. We show that in tumor cells expressing MAGE-A1,
      the 5' region is significantly less methylated than the other parts of the gene.
      The process leading to this site-specific hypomethylation does not appear to be
      permanent in these tumor cells, since in vitro-methylated MAGE-A1 sequences do
      not undergo demethylation after being stably transfected. However, in these cells
      there is a process that inhibits de novo methylation within the 5' region of MAGE
      A1, since unmethylated MAGE-A1 transgenes undergo remethylation at all CpGs
      except those located within the 5' region. This local inhibition of methylation
      appears to depend on promoter activity. We conclude that the site-specific
      hypomethylation of MAGE-A1 in tumor cells relies on a transient process of
      demethylation followed by a persistent local inhibition of remethylation due to
      the presence of transcription factors.

PMID- 15143171
TI  - The Rpd3-Sin3 histone deacetylase regulates replication timing and enables intra
      S origin control in Saccharomyces cerevisiae.
AB  - The replication of eukaryotic genomes follows a temporally staged program, in
      which late origin firing often occurs within domains of altered chromatin
      structure(s) and silenced genes. Histone deacetylation functions in gene
      silencing in some late-replicating regions, prompting an investigation of the
      role of histone deacetylation in replication timing control in Saccharomyces
      cerevisiae. Deletion of the histone deacetylase Rpd3 or its interacting partner
      Sin3 caused early activation of late origins at internal chromosomal loci but did
      not alter the initiation timing of early origins or a late-firing, telomere
      proximal origin. By delaying initiation relative to the earliest origins, Rpd3
      enables regulation of late origins by the intra-S replication checkpoint. RPD3
      deletion suppresses the slow S phase of clb5Delta cells by enabling late origins
      to fire earlier, suggesting that Rpd3 modulates the initiation timing of many
      origins throughout the genome. Examination of factors such as Ume6 that function
      together with Rpd3 in transcriptional repression indicates that Rpd3 regulates
      origin initiation timing independently of its role in transcriptional repression.
      This supports growing evidence that for much of the S. cerevisiae genome
      transcription and replication timing are not linked.

PMID- 15143174
TI  - Identification of a distinctive mutation spectrum associated with high levels of
      transcription in yeast.
AB  - High levels of transcription are associated with increased mutation rates in
      Saccharomyces cerevisiae, a phenomenon termed transcription-associated mutation
      (TAM). To obtain insight into the mechanism of TAM, we obtained LYS2 forward
      mutation spectra under low- versus high-transcription conditions in which LYS2
      was expressed from either the low-level pLYS2 promoter or the strong pGAL1-10
      promoter, respectively. Because of the large size of the LYS2 locus, forward
      mutations first were mapped to specific LYS2 subregions, and then those mutations
      that occurred within a defined 736-bp target region were sequenced. In the low
      transcription strain base substitutions comprised the majority (64%) of
      mutations, whereas short insertion-deletion mutations predominated (56%) in the
      high-transcription strain. Most notably, deletions of 2 nucleotides (nt)
      comprised 21% of the mutations in the high-transcription strain, and these events
      occurred predominantly at 5'-(G/C)AAA-3' sites. No -2 events were present in the
      low-transcription spectrum, thus identifying 2-nt deletions as a unique
      mutational signature for TAM.

PMID- 15143173
TI  - Role of CTCF binding sites in the Igf2/H19 imprinting control region.
AB  - A approximately 2.4-kb imprinting control region (ICR) regulates somatic
      monoallelic expression of the Igf2 and H19 genes. This is achieved through DNA
      methylation-dependent chromatin insulator and promoter silencing activities on
      the maternal and paternal chromosomes, respectively. In somatic cells, the
      hypomethylated maternally inherited ICR binds the insulator protein CTCF at four
      sites and blocks activity of the proximal Igf2 promoter by insulating it from its
      distal enhancers. CTCF binding is thought to play a direct role in inhibiting
      methylation of the ICR in female germ cells and in somatic cells and, therefore,
      in establishing and maintaining imprinting of the Igf2/H19 region. Here, we
      report on the effects of eliminating ICR CTCF binding by severely mutating all
      four sites in mice. We found that in the female and male germ lines, the mutant
      ICR remained hypomethylated and hypermethylated, respectively, showing that the
      CTCF binding sites are dispensable for imprinting establishment.
      Postfertilization, the maternal mutant ICR acquired methylation, which could be
      explained by loss of methylation inhibition, which is normally provided by CTCF
      binding. Adjacent regions in cis-the H19 promoter and gene-also acquired
      methylation, accompanied by downregulation of H19. This could be the result of a
      silencing effect of the methylated maternal ICR.

PMID- 15143175
TI  - The homeodomain protein CDP regulates mammary-specific gene transcription and
      tumorigenesis.
AB  - The CCAAT-displacement protein (CDP) has been implicated in developmental and
      cell-type-specific regulation of many cellular and viral genes. We previously
      have shown that CDP represses mouse mammary tumor virus (MMTV) transcription in
      tissue culture cells. Since CDP-binding activity for the MMTV long terminal
      repeat declines during mammary development, we tested whether binding mutations
      could alter viral expression. Infection of mice with MMTV proviruses containing
      CDP binding site mutations elevated viral RNA levels in virgin mammary glands and
      shortened mammary tumor latency. To determine if CDP has direct effects on MMTV
      transcription rather than viral spread, virgin mammary glands of homozygous CDP
      mutant mice lacking one of three Cut repeat DNA-binding domains (DeltaCR1) were
      examined by reverse transcription-PCR. RNA levels of endogenous MMTV as well as
      alpha-lactalbumin and whey acidic protein (WAP) were elevated. Heterozygous mice
      with a different CDP mutation that eliminated the entire C terminus and the
      homeodomain (DeltaC mice) showed increased levels of MMTV, beta-casein, WAP, and
      alpha-lactalbumin RNA in virgin mammary glands compared to those from wild-type
      animals. No differences in amounts of WDNM1, epsilon-casein, or glyceraldehyde-3
      phosphate dehydrogenase RNA were observed between the undifferentiated mammary
      tissues from wild-type and mutant mice, indicating the specificity of this
      effect. These data show independent contributions of different CDP domains to
      negative regulation of differentiation-specific genes in the mammary gland.

PMID- 15143176
TI  - Paired-type homeodomain transcription factors are imported into the nucleus by
      karyopherin 13.
AB  - We report that the paired homeodomain transcription factor Pax6 is imported into
      the nucleus by the Karyopherin beta family member Karyopherin 13 (Kap13). Pax6
      was identified as a potential cargo for Kap13 by a yeast two-hybrid screen.
      Direct binding of Pax6 to Kap13 was subsequently confirmed by in vitro assays
      with recombinant proteins, and binding in vivo was shown by
      coimmunoprecipitation. Ran-dependent import of Pax6 by Kap13 was shown to occur
      by using a digitonin-permeabilized cells assay. Kap13 binds to Pax6 via a nuclear
      localization sequence (NLS), which is located within a segment of 80 amino acid
      residues that includes the homeodomain. Kap13 showed reduced binding to Pax6 when
      either region located at each end of the homeodomain (208 to 214 and 261 to 267)
      was deleted. The paired-type homeodomain transcription factor family includes
      more than 20 members. All members contain a region similar to the NLS found in
      Pax6 and are therefore likely to be imported by Kap13. We confirmed this
      hypothesis for Pax3 and Crx, which bind to and are imported by Kap13.

PMID- 15143177
TI  - Distinct domains of AU-rich elements exert different functions in mRNA
      destabilization and stabilization by p38 mitogen-activated protein kinase or HuR.
AB  - AU-rich elements (AREs) control the expression of numerous genes by accelerating
      the decay of their mRNAs. Rapid decay and deadenylation of beta-globin mRNA
      containing AU-rich 3' untranslated regions of the chemoattractant cytokine
      interleukin-8 (IL-8) are strongly attenuated by activating the p38 mitogen
      activated protein (MAP) kinase/MAP kinase-activated protein kinase 2 (MK2)
      pathway. Further evidence for a crucial role of the poly(A) tail is provided by
      the loss of destabilization and kinase-induced stabilization in ARE RNAs
      expressed as nonadenylated forms by introducing a histone stem-loop sequence. The
      minimal regulatory element in the IL-8 mRNA is located in a 60-nucleotide
      evolutionarily conserved sequence with a structurally and functionally bipartite
      character: a core domain with four AUUUA motifs and limited destabilizing
      function on its own and an auxiliary domain that markedly enhances
      destabilization exerted by the core domain and thus is essential for the rapid
      removal of RNA targets. A similar bipartite structure and function are observed
      for the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE.
      Stabilization in response to p38/MK2 activation is seen with the core domain
      alone and also after mutation of the AUUUA motifs in the complete IL-8 ARE.
      Stabilization by ARE binding protein HuR requires different sequence elements.
      Binding but no stabilization is observed with the IL-8 ARE. Responsiveness to HuR
      is gained by exchanging the auxiliary domain of the IL-8 ARE with that of GM-CSF
      or with a domain of the c-fos ARE, which results in even stronger responsiveness.
      These results show that distinct ARE domains differ in function with regard to
      destabilization, stabilization by p38/MK2 activation, and stabilization by HuR.

PMID- 15143178
TI  - The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for
      maturation of cytosolic Fe/S proteins.
AB  - Iron-sulfur (Fe/S) proteins are located in mitochondria, cytosol, and nucleus.
      Mitochondrial Fe/S proteins are matured by the iron-sulfur cluster (ISC) assembly
      machinery. Little is known about the formation of Fe/S proteins in the cytosol
      and nucleus. A function of mitochondria in cytosolic Fe/S protein maturation has
      been noted, but small amounts of some ISC components have been detected outside
      mitochondria. Here, we studied the highly conserved yeast proteins Isu1p and
      Isu2p, which provide a scaffold for Fe/S cluster synthesis. We asked whether the
      Isu proteins are needed for biosynthesis of cytosolic Fe/S clusters and in which
      subcellular compartment the Isu proteins are required. The Isu proteins were
      found to be essential for de novo biosynthesis of both mitochondrial and
      cytosolic Fe/S proteins. Several lines of evidence indicate that Isu1p and Isu2p
      have to be located inside mitochondria in order to perform their function in
      cytosolic Fe/S protein maturation. We were unable to mislocalize Isu1p to the
      cytosol due to the presence of multiple, independent mitochondrial targeting
      signals in this protein. Further, the bacterial homologue IscU and the human Isu
      proteins (partially) complemented the defects of yeast Isu protein-depleted cells
      in growth rate, Fe/S protein biogenesis, and iron homeostasis, yet only after
      targeting to mitochondria. Together, our data suggest that the Isu proteins need
      to be localized in mitochondria to fulfill their functional requirement in Fe/S
      protein maturation in the cytosol.

PMID- 15143179
TI  - Parent-of-origin-specific binding of nuclear hormone receptor complexes in the
      H19-Igf2 imprinting control region.
AB  - Parent-of-origin-specific expression of the mouse insulin-like growth factor 2
      gene (Igf2) and the closely linked H19 gene located on distal chromosome 7 is
      regulated by a 2.4-kb imprinting control region (ICR) located upstream of the H19
      gene. In somatic cells, the maternally and paternally derived ICRs are hypo- and
      hypermethylated, respectively, with the former binding the insulator protein
      CCCTC-binding factor (CTCF) and acting to block access of enhancers to the Igf2
      promoter. Here we report on a detailed in vivo footprinting analysis-using
      ligation-mediated PCR combined with in vivo dimethyl sulfate, DNase I, or UV
      treatment-of ICR sequences located outside of the CTCF binding domains. In mouse
      primary embryo fibroblasts carrying only maternal or paternal copies of distal
      chromosome 7, we have identified five prominent footprints specific to the
      maternal ICR. Each of the five footprinted areas contains at least two nuclear
      hormone receptor hexad binding sites arranged with irregular spacing. When
      combined with fibroblast nuclear extracts, these sequences interact with
      complexes containing retinoic X receptor alpha and estrogen receptor beta. More
      significantly, the footprint sequences bind nuclear hormone receptor complexes in
      male, but not female, germ cell extracts purified from fetuses at a developmental
      stage corresponding to the time of establishment of differential ICR methylation.
      These data are consistent with the possibility that nuclear hormone receptor
      complexes participate in the establishment of differential ICR methylation
      imprinting in the germ line.

PMID- 15143180
TI  - The nuclear pore complex and the DEAD box protein Rat8p/Dbp5p have nonessential
      features which appear to facilitate mRNA export following heat shock.
AB  - Nuclear pore complexes (NPCs) play an essential role in RNA export. Nucleoporins
      required for mRNA export in Saccharomyces cerevisiae are found in the Nup84p and
      Nup82p subcomplexes of the NPC. The Nup82p subcomplex contains Nup82p,
      Rat7p/Nup159p, Nsp1p, Gle1p/Rss1p, and Rip1p/Nup42p and is found only on the
      cytoplasmic face of NPCs. Both Rat7p and Gle1p contain binding sites for
      Rat8p/Dbp5p, an essential DEAD box protein and putative RNA helicase. Rip1p
      interacts directly with Gle1p and is the only protein known to be essential for
      mRNA export after heat shock but not under normal growth conditions. We report
      that in cells lacking Rip1p, both Gle1p and Rat8p dissociate from NPCs following
      heat shock at 42 degrees C. Rat8p but not Gle1p was retained at NPCs if rip1Delta
      cells were first shifted to 37 degrees C and then to 42 degrees C, and this was
      correlated with preserving mRNA export in heat-shocked rip1Delta cells. Export
      following ethanol shock was less dependent on the presence of Rip1p. Exposure to
      10% ethanol led to dissociation of Rat8p from NPCs in both wild-type and
      rip1Delta cells. Following this treatment, Rat8p was primarily nuclear in wild
      type cells but primarily cytoplasmic in rip1Delta cells. We also determined that
      efficient export of heat shock mRNA after heat shock depends upon a novel 6-amino
      acid element within Rat8p. This motif is not required under normal growth
      conditions or following ethanol shock. These studies suggest that the molecular
      mechanism responsible for the defect in export of heat shock mRNAs in heat
      shocked rip1Delta cells is dissociation of Rat8p from NPCs. These studies also
      suggest that both nuclear pores and Rat8p have features not required for mRNA
      export in growing cells but which enhance the ability of mRNAs to be exported
      following heat shock.

PMID- 15143181
TI  - Amphoterin stimulates myogenesis and counteracts the antimyogenic factors basic
      fibroblast growth factor and S100B via RAGE binding.
AB  - The receptor for advanced glycation end products (RAGE), a multiligand receptor
      of the immunoglobulin superfamily, has been implicated in the inflammatory
      response, diabetic angiopathy and neuropathy, neurodegeneration, cell migration,
      tumor growth, neuroprotection, and neuronal differentiation. We show here that
      (i) RAGE is expressed in skeletal muscle tissue and its expression is
      developmentally regulated and (ii) RAGE engagement by amphoterin (HMGB1), a RAGE
      ligand, in rat L6 myoblasts results in stimulation of myogenic differentiation
      via activation of p38 mitogen-activated protein kinase (MAPK), up-regulation of
      myogenin and myosin heavy chain expression, and induction of muscle creatine
      kinase. No such effects were detected in myoblasts transfected with a RAGE mutant
      lacking the transducing domain or myoblasts transfected with a constitutively
      inactive form of the p38 MAPK upstream kinase, MAPK kinase 6, Cdc42, or Rac-1.
      Moreover, amphoterin counteracted the antimyogenic activity of the Ca(2+)
      modulated protein S100B, which was reported to inhibit myogenic differentiation
      via inactivation of p38 MAPK, and basic fibroblast growth factor (bFGF), a known
      inhibitor of myogenic differentiation, in a manner that was inversely related to
      the S100B or bFGF concentration and directly related to the extent of RAGE
      expression. These data suggest that RAGE and amphoterin might play an important
      role in myogenesis, accelerating myogenic differentiation via Cdc42-Rac-1-MAPK
      kinase 6-p38 MAPK.

PMID- 15143183
TI  - Functional studies of shaggy/glycogen synthase kinase 3 phosphorylation sites in
      Drosophila melanogaster.
AB  - Early studies of glycogen synthase kinase 3 (GSK-3) in mammalian systems focused
      on its pivotal role in glycogen metabolism and insulin-mediated signaling. It is
      now recognized that GSK-3 is central to a number of diverse signaling systems.
      Here, we show that the major form of the kinase Shaggy (Sgg), the GSK-3 fly
      ortholog, is negatively regulated during insulin-like/phosphatidylinositol 3
      kinase (PI3K) signaling in vivo. Since genetic studies of Drosophila melanogaster
      had previously shown that Wingless (Wg) signaling also acts to antagonize Sgg, we
      investigate how the kinase might integrate, or else discriminate, signaling
      inputs by Wg and insulin. Using Drosophila cell line assays, we found, in
      contrast to previous reports, that Wg induces accumulation of its transducer
      Armadillo (Arm)/beta-catenin without significant alteration of global Sgg
      specific activity. In agreement with a previous study using human GSK-3beta, Wg
      did not cause phosphorylation changes of the Ser9 or Tyr214 regulatory
      phosphorylated sites of Sgg. Conversely, as shown in mammalian systems, insulin
      induced inhibition of Sgg-specific activity by phosphorylation at the N-terminal
      pseudosubstrate site (Ser9) did not induce Arm/beta-catenin accumulation, showing
      selectivity in response to the different signaling pathways. Interestingly, a
      minigene bearing a Ser9-to-Ala change rescued mutant sgg without causing abnormal
      development, suggesting that the regulation of Sgg via the inhibitory
      pseudosubstrate domain is dispensable for many aspects of its function. Our
      studies of Drosophila show that Wg and insulin or PI3K pathways do not converge
      on Sgg but that they exhibit cross-regulatory interactions.

PMID- 15143182
TI  - Regulation of constitutive p50/c-Rel activity via proteasome inhibitor-resistant
      IkappaBalpha degradation in B cells.
AB  - Constitutive NF-kappaB activity has emerged as an important cell survival
      component of physiological and pathological processes, including B-cell
      development. In B cells, constitutive NF-kappaB activity includes p50/c-Rel and
      p52/RelB heterodimers, both of which are critical for proper B-cell development.
      We previously reported that WEHI-231 B cells maintain constitutive p50/c-Rel
      activity via selective degradation of IkappaBalpha that is mediated by a
      proteasome inhibitor-resistant, now termed PIR, pathway. Here, we examined the
      mechanisms of PIR degradation by comparing it to the canonical pathway that
      involves IkappaB kinase-dependent phosphorylation and beta-TrCP-dependent
      ubiquitylation of the N-terminal signal response domain of IkappaBalpha. We found
      a distinct consensus sequence within this domain of IkappaBalpha for PIR
      degradation. Chimeric analyses of IkappaBalpha and IkappaBbeta further revealed
      that the ankyrin repeats of IkappaBalpha, but not IkappaBbeta, contained
      information necessary for PIR degradation, thereby explaining IkappaBalpha
      selectivity for the PIR pathway. Moreover, we found that PIR degradation of
      IkappaBalpha and constitutive p50/c-Rel activity in primary murine B cells were
      maintained in a manner different from B-cell-activating-factor-dependent p52/RelB
      regulation. Thus, our findings suggest that nonconventional PIR degradation of
      IkappaBalpha may play a physiological role in the development of B cells in vivo.

PMID- 15143184
TI  - Selective modification of eukaryotic initiation factor 4F (eIF4F) at the onset of
      cell differentiation: recruitment of eIF4GII and long-lasting phosphorylation of
      eIF4E.
AB  - mRNA translation is mainly regulated at the level of initiation, a process that
      involves the synergistic action of the 5' cap structure and the 3' poly(A) tail
      at the ends of eukaryotic mRNA. The eukaryote initiation factor 4G(eIF4G) is a
      pivotal scaffold protein that forms a critical link between mRNA cap structure,
      poly(A) tail, and the small ribosomal subunit. There are two functional homologs
      of eIF4G in mammals, the original eIF4G, renamed eIF4GI, and eIF4GII that
      functionally complements eIF4GI. To date, biochemical and functional analysis
      have not identified differential activities for eIF4GI and eIF4GII. In this
      report, we demonstrate that eIF4GII, but not eIF4GI, is selectively recruited to
      capped mRNA at the onset of cell differentiation. This recruitment is coincident
      with a strong and long-lasting phosphorylation of eIF4E and the release of 4E
      BP1, a suppressor of eIF4E function, from the cap structure, without a
      concomitant change in 4E-BP1's phosphorylation. Our data further indicate that
      cytokines such as thrombopoietin can differentially regulate eIF4GI/II
      activities. These results provide the first evidence that eIF4GI/II does fulfill
      selective roles in mammalian cells.

PMID- 15143185
TI  - Molecular and genetic characterization of a Taf1p domain essential for yeast
      TFIID assembly.
AB  - Yeast Taf1p is an integral component of the multiprotein transcription factor
      TFIID. By using coimmunoprecipitation assays, coupled with a comprehensive set of
      deletion mutants encompassing the entire open reading frame of TAF1, we have
      discovered an essential role of a small portion of yeast Taf1p. This domain of
      Taf1p, termed region 4, consisting of amino acids 200 to 303, contributes
      critically to the assembly and stability of the 15-subunit TFIID holocomplex.
      Region 4 of Taf1p is mutationally sensitive, can assemble several Tafps into a
      partial TFIID complex, and interacts directly with Taf4p and Taf6p. Mutations in
      Taf1p-region 4 induce temperature-conditional growth of yeast cells. At the
      nonpermissive temperature these mutations have drastic effects on both TFIID
      integrity and mRNA synthesis. These data are consistent with the hypothesis that
      Taf1p subserves a critical scaffold function within the TFIID complex. The
      significance of these data with regard to TFIID structure and function is
      discussed.

PMID- 15143186
TI  - Signaling specificity by Ras family GTPases is determined by the full spectrum of
      effectors they regulate.
AB  - Ras family GTPases (RFGs) regulate signaling pathways that control multiple
      biological processes. How signaling specificity among the closely related family
      members is achieved is poorly understood. We have taken a proteomics approach to
      signaling by RFGs, and we have analyzed interactions of a panel of RFGs with a
      comprehensive group of known and potential effectors. We have found remarkable
      differences in the ability of RFGs to regulate the various isoforms of known
      effector families. We have also identified several proteins as novel effectors of
      RFGs with differential binding specificities to the various RFGs. We propose that
      specificity among RFGs is achieved by the differential regulation of combinations
      of effector families as well as by the selective regulation of different isoforms
      within an effector family. An understanding of this new level of complexity in
      the signaling pathways regulated by RFGs is necessary to understand how they
      carry out their many cellular functions. It will also likely have critical
      implications in the treatment of human diseases such as cancer.

PMID- 15143188
TI  - Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling.
AB  - Jak family tyrosine kinases mediate signaling by cytokine receptors to regulate
      diverse biological processes. Although Jak2 and other Jak kinase family members
      are phosphorylated on numerous sites during cytokine signaling, the identity and
      function of most of these sites remains unknown. Using tandem mass spectroscopic
      analysis of activated Jak2 protein from intact cells, we identified Tyr(221) and
      Tyr(570) as novel sites of Jak2 phosphorylation. Phosphorylation of both sites
      was stimulated by cytokine treatment of cultured cells, and this stimulation
      required Jak2 kinase activity. While we observed no gross alteration of signaling
      upon mutation of Tyr(221), Tyr(570) lies within the inhibitory JH2 domain of
      Jak2, and mutation of this site (Jak2(Y570F)) results in constitutive Jak2
      dependent signaling in the absence of cytokine stimulation and enhances and
      prolongs Jak2 activation during cytokine stimulation. Mutation of Tyr(570) does
      not alter the ability of SOCS3 to bind or inhibit Jak2, however. Thus, the
      phosphorylation of Tyr(570) in vivo inhibits Jak2-dependent signaling
      independently of SOCS3-mediated inhibition. This Tyr(570)-dependent mechanism of
      Jak2 inhibition likely represents an important mechanism by which cytokine
      function is regulated.

PMID- 15143187
TI  - Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.
AB  - The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in
      the cytokine/hematopoietin receptor superfamily and is a component of signaling
      by insulin receptor and several G-protein-coupled receptors. However, there is
      only limited knowledge of the physical structure of JAK2 or which of the 49
      tyrosines in JAK2 are autophosphorylated. In this study, mass spectrometry and
      two-dimensional peptide mapping were used to determine that tyrosines 221, 570,
      and 1007 in JAK2 are autophosphorylated. Phosphorylation of tyrosine 570 is
      particularly robust. In response to growth hormone, JAK2 was rapidly and
      transiently phosphorylated at tyrosines 221 and 570, returning to basal levels by
      60 min. Analysis of the sequences surrounding tyrosines 221 and 570 in JAK2 and
      tyrosines in other proteins that are phosphorylated in response to ligands that
      activate JAK2 suggests that the YXX[L/I/V] motif is one of the motifs recognized
      by JAK2. Experiments using JAK2 with tyrosines 221 and 570 mutated to
      phenylalanine suggest that tyrosines 221 and 570 in JAK2 may serve as regulatory
      sites in JAK2, with phosphorylation of tyrosine 221 increasing kinase activity
      and phosphorylation of tyrosine 570 decreasing kinase activity and thereby
      contributing to rapid termination of ligand activation of JAK2.

PMID- 15143191
TI  - Overexpression of the ped/pea-15 gene causes diabetes by impairing glucose
      stimulated insulin secretion in addition to insulin action.
AB  - Overexpression of the ped/pea-15 gene is a common feature of type 2 diabetes. In
      the present work, we show that transgenic mice ubiquitously overexpressing
      ped/pea-15 exhibited mildly elevated random-fed blood glucose levels and
      decreased glucose tolerance. Treatment with a 60% fat diet led ped/pea-15
      transgenic mice to develop diabetes. Consistent with insulin resistance in these
      mice, insulin administration reduced glucose levels by only 35% after 45 min,
      compared to 70% in control mice. In vivo, insulin-stimulated glucose uptake was
      decreased by almost 50% in fat and muscle tissues of the ped/pea-15 transgenic
      mice, accompanied by protein kinase Calpha activation and block of insulin
      induction of protein kinase Czeta. These changes persisted in isolated adipocytes
      from the transgenic mice and were rescued by the protein kinase C inhibitor
      bisindolylmaleimide. In addition to insulin resistance, ped/pea-15 transgenic
      mice showed a 70% reduction in insulin response to glucose loading. Stable
      overexpression of ped/pea-15 in the glucose-responsive MIN6 beta-cell line also
      caused protein kinase Calpha activation and a marked decline in glucose
      stimulated insulin secretion. Antisense block of endogenous ped/pea-15 increased
      glucose sensitivity by 2.5-fold in these cells. Thus, in vivo, overexpression of
      ped/pea-15 may lead to diabetes by impairing insulin secretion in addition to
      insulin action.

PMID- 15143189
TI  - Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its
      nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels.
AB  - The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of
      actin dynamics and localizes to the tips of lamellipodia and filopodia. Here, we
      show that Abi-1 binds the actin nucleator protein Wave-1 through an amino
      terminal Wave-binding (WAB) domain and that disruption of the Abi-1-Wave-1
      interaction prevents Abi-1 from reaching the tip of the lamellipodium. Abi-1
      binds to the Wave homology domain of Wave-1, a region that is required for
      translocation of Wave-1 to the lamellipodium. Mouse embryo fibroblasts that lack
      one allele of Abi-1 and are homozygous null for the related Abi-2 protein exhibit
      decreased Wave-1 protein levels. This phenotype is rescued by Abi-1 proteins that
      retain Wave-1 binding but not by Abi-1 mutants that cannot bind to Wave-1.
      Moreover, we uncovered an overlapping SNARE domain in the amino terminus of Abi-1
      that interacts with Syntaxin-1, a SNARE family member. Further, we demonstrated
      that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent
      manner and that complete nuclear translocation of Abi-1 in the absence of LMB
      requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1.
      Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading
      edge to regulate Wave-1 localization and protein levels.

PMID- 15143190
TI  - The nuclear hormone receptor coactivator NRC is a pleiotropic modulator affecting
      growth, development, apoptosis, reproduction, and wound repair.
AB  - Nuclear hormone receptor coregulator (NRC) is a 2,063-amino-acid coregulator of
      nuclear hormone receptors and other transcription factors (e.g., c-Fos, c-Jun,
      and NF-kappaB). We and others have generated C57BL/6-129S6 hybrid (C57/129)
      NRC(+/-) mice that appear outwardly normal and grow and reproduce. In contrast,
      homozygous deletion of the NRC gene is embryonic lethal. NRC(-/-) embryos are
      always smaller than NRC(+/+) embryos, and NRC(-/-) embryos die between 8.5 and
      12.5 days postcoitus (dpc), suggesting that NRC has a pleotrophic effect on
      growth. To study this, we derived mouse embryonic fibroblasts (MEFs) from 12.5
      dpc embryos, which revealed that NRC(-/-) MEFs exhibit a high rate of apoptosis.
      Furthermore, a small interfering RNA that targets mouse NRC leads to enhanced
      apoptosis of wild-type MEFs. The finding that C57/129 NRC(+/-) mice exhibit no
      apparent phenotype prompted us to develop 129S6 NRC(+/-) mice, since the
      phenotype(s) of certain gene deletions may be strain dependent. In contrast with
      C57/129 NRC(+/-) females, 20% of 129S6 NRC(+/-) females are infertile while 80%
      are hypofertile. The 129S6 NRC(+/-) males produce offspring when crossed with
      wild-type 129S6 females, although fertility is reduced. The 129S6 NRC(+/-) mice
      tend to be stunted in their growth compared with their wild-type littermates and
      exhibit increased postnatal mortality. Lastly, both C57/129 NRC(+/-) and 129S6
      NRC(+/-) mice exhibit a spontaneous wound healing defect, indicating that NRC
      plays an important role in that process. Our findings reveal that NRC is a
      coregulator that controls many cellular and physiologic processes ranging from
      growth and development to reproduction and wound repair.

PMID- 15143192
TI  - Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome
      genes him-6, rad-51, and top-3 are needed to maintain genome stability in the
      germ line.
AB  - Bloom's syndrome (BS) is an autosomal-recessive human disorder caused by
      mutations in the BS RecQ helicase and is associated with loss of genomic
      integrity and an increased incidence of cancer. We analyzed the mitotic and the
      meiotic roles of Caenorhabditis elegans him-6, which we show to encode the
      ortholog of the human BS gene. Mutations in him-6 result in an enhanced
      irradiation sensitivity, a partially defective S-phase checkpoint, and in reduced
      levels of DNA-damage induced apoptosis. Furthermore, him-6 mutants exhibit a
      decreased frequency of meiotic recombination that is probably due to a defect in
      the progression of crossover recombination. In mitotically proliferating germ
      cells, our genetic interaction studies, as well as the assessment of the number
      of double-strand breaks via RAD-51 foci, reveal a complex regulatory network that
      is different from the situation in yeast. Although the number of double-strand
      breaks in him-6 and top-3 single mutants is elevated, the combined depletion of
      him-6 and top-3 leads to mitotic catastrophe concomitant with a massive increase
      in the level of double-strand breaks, a phenotype that is completely suppressed
      by rad-51. him-6 and top-3 are thus needed to maintain low levels of double
      strand breaks in normally proliferating germ cells, and both act in partial
      redundant pathways downstream of rad-51 to prevent mitotic catastrophy. Finally,
      we show that topoisomerase IIIalpha acts independently during a late stage of
      meiotic recombination.

PMID- 15143193
TI  - Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex.
AB  - The Cdx1 gene product is essential for normal anterior-posterior vertebral
      patterning. Expression of Cdx1 is regulated by several pathways implicated in
      anterior-posterior patterning events, including retinoid and Wnt signaling. We
      have previously shown that retinoic acid plays a key role in early stages of Cdx1
      expression at embryonic day 7.5 (E7.5), while both Wnt3a signaling and an
      autoregulatory loop, dependent on Cdx1 itself, are involved in later stages of
      expression (E8.5 to E9.5). This autoregulation is reflected by the ability of
      Cdx1 to affect expression from proximal Cdx1 promoter sequences in tissue
      culture. However, this region is devoid of a demonstrable Cdx response
      element(s). We have now found that Cdx1 and LEF1, a nuclear effector of Wnt
      signaling, synergize to induce expression from the Cdx1 promoter through
      previously documented LEF/T-cell factor response elements. We also found a direct
      physical interaction between the homeodomain of Cdx1 and the B box of LEF1,
      suggesting a basis for this synergy. Consistent with these observations, analysis
      of Cdx1 Wnt3a(vt) compound mutants demonstrated that Wnt and Cdx1 converged on
      Cdx1 expression and vertebral patterning in vivo. Further data suggest that Cdx
      high-mobility group box interactions might be involved in a number of additional
      pathways.

PMID- 15143194
TI  - Jak3-independent trafficking of the common gamma chain receptor subunit:
      chaperone function of Jaks revisited.
AB  - Janus kinases (Jaks) play an essential role in cytokine signaling and have been
      reported to regulate plasma membrane expression of their cognate receptors. In
      this study, we examined whether Jak3 and the common gamma chain (gamma(c))
      reciprocally regulate their plasma membrane expression. In contrast to
      interleukin-2Ralpha, gamma(c) localized poorly to the plasma membrane and
      accumulated in endosomal-lysosomal compartments. However, gamma(c) was expressed
      at comparable levels on the surface of cells lacking Jak3, and plasma membrane
      turnover of gamma(c) was independent of Jak3. Nonetheless, overexpression of Jak3
      enhanced accumulation of gamma(c) at the plasma membrane. Without gamma(c), Jak3
      localized in the cytosol, whereas in the presence of the receptor, it colocalized
      with gamma(c) in endosomes and at the plasma membrane. Although the Jak FERM
      domain is necessary and sufficient for receptor binding, the requirement for full
      length Jak3 in gamma(c) membrane trafficking was remarkably stringent; using
      truncation and deletion mutants, we showed that the entire Jak3 molecule was
      required, although kinase activity was not. Thus, unlike other cytokine
      receptors, gamma(c) does not require Jak3 for receptor membrane expression.
      However, full-length Jak3 is required for normal trafficking of this cytokine
      receptor/Jak pair, a finding that has important structural and clinical
      implications.

PMID- 15143196
TI  - Ionizing radiation induces delayed hyperrecombination in Mammalian cells.
AB  - Exposure to ionizing radiation can result in delayed effects that can be detected
      in the progeny of an irradiated cell multiple generations after the initial
      exposure. These effects are described under the rubric of radiation-induced
      genomic instability and encompass multiple genotoxic endpoints. We have developed
      a green fluorescence protein (GFP)-based assay and demonstrated that ionizing
      radiation induces genomic instability in human RKO-derived cells and in human
      hamster hybrid GM10115 cells, manifested as increased homologous recombination
      (HR). Up to 10% of cells cultured after irradiation produce mixed GFP(+/-)
      colonies indicative of delayed HR or, in the case of RKO-derived cells, mutation
      and deletion. Consistent with prior studies, delayed chromosomal instability
      correlated with delayed reproductive cell death. In contrast, cells displaying
      delayed HR showed no evidence of delayed reproductive cell death, and there was
      no correlation between delayed chromosomal instability and delayed HR, indicating
      that these forms of genome instability arise by distinct mechanisms. Because
      delayed hyperrecombination can be induced at doses of ionizing radiation that are
      not associated with significantly reduced cell viability, these data may have
      important implications for assessment of radiation risk and understanding the
      mechanisms of radiation carcinogenesis.

PMID- 15143199
TI  - Activity-dependent synaptic competition at mammalian neuromuscular junctions.
AB  - Synapse elimination is a widespread developmental process in the peripheral and
      central nervous system that brings about refinement of neural connections through
      epigenetic mechanisms. Here we describe recent advances concerning the role of
      the pattern of motoneuronal firing, synchronous or asynchronous, in neuromuscular
      synapse elimination.

PMID- 15143195
TI  - Regulation of telomere length and suppression of genomic instability in human
      somatic cells by Ku86.
AB  - Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily
      disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been
      implicated in the regulation of telomere length although the effect of Ku86
      mutations varies considerably between species. Indeed, telomeres either shorten
      significantly, shorten slightly, remain unchanged, or lengthen significantly in
      budding yeast, fission yeast, chicken cells, or plants, respectively, that are
      null for Ku86 expression. Thus, it has been unclear which model system is most
      relevant for humans. We demonstrate here that the functional inactivation of even
      a single allele of Ku86 in human somatic cells results in profound telomere loss,
      which is accompanied by an increase in chromosomal fusions, translocations, and
      genomic instability. Together, these experiments demonstrate that Ku86, separate
      from its role in nonhomologous end joining, performs the additional function in
      human somatic cells of suppressing genomic instability through the regulation of
      telomere length.

PMID- 15143197
TI  - NHERF2 specifically interacts with LPA2 receptor and defines the specificity and
      efficiency of receptor-mediated phospholipase C-beta3 activation.
AB  - Lysophosphatidic acid (LPA) activates a family of cognate G protein-coupled
      receptors and is involved in various pathophysiological processes. However, it is
      not clearly understood how these LPA receptors are specifically coupled to their
      downstream signaling molecules. This study found that LPA(2), but not the other
      LPA receptor isoforms, specifically interacts with Na(+)/H(+) exchanger
      regulatory factor2 (NHERF2). In addition, the interaction between them requires
      the C-terminal PDZ domain-binding motif of LPA(2) and the second PDZ domain of
      NHERF2. Moreover, the stable expression of NHERF2 potentiated LPA-induced
      phospholipase C-beta (PLC-beta) activation, which was markedly attenuated by
      either a mutation in the PDZ-binding motif of LPA(2) or by the gene silencing of
      NHERF2. Using its second PDZ domain, NHERF2 was found to indirectly link LPA(2)
      to PLC-beta3 to form a complex, and the other PLC-beta isozymes were not included
      in the protein complex. Consistently, LPA(2)-mediated PLC-beta activation was
      specifically inhibited by the gene silencing of PLC-beta3. In addition, NHERF2
      increases LPA-induced ERK activation, which is followed by cyclooxygenase-2
      induction via a PLC-dependent pathway. Overall, the results suggest that a
      ternary complex composed of LPA(2), NHERF2, and PLC-beta3 may play a key role in
      the LPA(2)-mediated PLC-beta signaling pathway.

PMID- 15143200
TI  - How free fatty acids inhibit glucose utilization in human skeletal muscle.
AB  - Rat muscle studies suggest competition between free fatty acids (FFA) and glucose
      for oxidation, resulting in glucose-6-phosphate accumulation. However, FFA
      decrease glucose-6-phosphate in human skeletal muscle, indicating direct
      inhibition of glucose transport/phosphorylation. This mechanism could redirect
      glucose from muscle to brain during fasting and explain the insulin resistance
      associated with high-lipid diets and obesity.

PMID- 15143201
TI  - Aldosterone: refreshing a slow hormone by swift action.
AB  - Aldosterone elicits not only genomic effects with physiological consequences
      within hours or days but also elicits rapid nongenomic effects, such as
      activation of sodium transport in target cells, within seconds or minutes. Rapid
      aldosterone effects, which have also been shown in several in vivo studies in
      humans (e.g., increase in peripheral vascular resistance and blood pressure), are
      of potential clinical importance.

PMID- 15143198
TI  - Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5
      phosphate 4-kinase beta-/- mice.
AB  - Phosphorylated derivatives of the lipid phosphatidylinositol are known to play
      critical roles in insulin response. Phosphatidylinositol 5-phosphate 4-kinases
      convert phosphatidylinositol 5-phosphate to phosphatidylinositol 4,5-bis
      phosphate. To understand the physiological role of these kinases, we generated
      mice that do not express phosphatidylinositol 5-phosphate 4-kinase beta. These
      mice are hypersensitive to insulin and have reduced body weights compared to wild
      type littermates. While adult male mice lacking phosphatidylinositol 5-phosphate
      4-kinase beta have significantly less body fat than wild-type littermates, female
      mice lacking phosphatidylinositol 5-phosphate 4-kinase beta have increased
      insulin sensitivity in the presence of normal adiposity. Furthermore, in vivo
      insulin-induced activation of the protein kinase Akt is enhanced in skeletal
      muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase
      beta. These results indicate that phosphatidylinositol 5-phosphate 4-kinase beta
      plays a role in determining insulin sensitivity and adiposity in vivo and suggest
      that inhibitors of this enzyme may be useful in the treatment of type 2 diabetes.

PMID- 15143202
TI  - Olfaction: from odorant molecules to the olfactory cortex.
AB  - How do we smell? Our knowledge of how odor information from the environment is
      perceived has greatly advanced since the discovery of approximately 1,000 genes
      for odorant receptors in the mammalian genome. From the combination of molecular
      genetic, electrophysiological, and optical imaging studies a better understanding
      of how we smell is emerging.

PMID- 15143203
TI  - Use of recombinant congenic strains in mapping disease-modifying genes.
AB  - Previous research studies have established much information about single-gene
      diseases. However, other genes also influencing the outcome of a disease and
      genes involved in complex disease remain largely unknown. Here we report on
      recombinant congenic strains of mice, a powerful tool for genetic dissection of a
      complex trait.

PMID- 15143204
TI  - Neuroglobin: a respiratory protein of the nervous system.
AB  - Nerve tissues exhibit some of the highest oxygen consumption rates found in the
      body. Neuroglobin, a heme protein distantly related to hemoglobin, is thought to
      enhance the supply of oxygen to the neurons, the eye, and some endocrine tissues.
      Neuroglobin may promote neuronal survival under hypoxic conditions as they occur,
      for example, in stroke.

PMID- 15143205
TI  - Proteomic strategies and their application in studies of renal function.
AB  - Proteomics is a promising new tool for functional genomics. In addition to two
      dimensional gel electrophoresis, other methods that are based on liquid
      chromatography and mass spectrometry are now available to study proteins. In this
      brief article, we review the strengths and limitations of the proteomic
      approaches currently available to the researcher, and we provide examples of how
      proteomics has been, and can in the future be, used to study the kidney.

PMID- 15143206
TI  - Role of superoxide as a signaling molecule.
AB  - Superoxide is known to affect vascular physiology in several ways and has also
      been recognized to contribute significantly to vascular physiopathology. Here we
      discuss the emerging role of superoxide as an essential signaling molecule in
      normal physiology.

PMID- 15143207
TI  - Morphological features of cell death.
AB  - Cell death is discriminated into two main forms: apoptosis and necrosis. In
      contrast to necrosis, apoptosis is a regulated, energy-dependent form of cell
      death leading to phagocytosis of cellular remnants by neighboring cells.
      Characteristic morphological features of these two forms of cell death will be
      discussed and correlated to underlying molecular mechanisms.

PMID- 15143208
TI  - The airway compartment: chambers of secrets.
AB  - The adhesion molecule intercellular adhesion molecule-1 (ICAM-1) is known to play
      a crucial role in lung inflammation such as endotoxin-induced injury. Although
      ICAM-1 has been characterized on endothelial cells, limited information is
      available regarding its expression in the epithelial compartment. The present
      review provides novel views on this aspect.

PMID- 15143209
TI  - "Vision" in single-celled algae.
AB  - Photosynthetic unicellular algae have a unique visual system. In Chlamydomonas
      reinhardtii, the pigmented eye comprises the optical system and at least five
      different rhodopsin photoreceptors. Two of them, the channelrhodopsins, are
      rhodopsin-ion channel hybrids switched between closed and open states by
      photoisomerization of the attached retinal chromophore. They promise to become a
      useful tool for noninvasive control of membrane potential and intracellular ion
      concentrations.

PMID- 15143210
TI  - The sarcoplasmic reticulum, Ca2+ trapping, and wave mechanisms in smooth muscle.
AB  - The sarcoplasmic reticulum (SR) and apposed regions of the sarcolemma passively
      trap Ca2+ entering the cell to limit the rise in cytoplasmic Ca2+ concentration
      without SR pump involvement. When "leaky," the SR facilitates Ca2+ entry to the
      cytoplasm. SR Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP(3)Rs)
      propagates as calcium waves; IP(3)Rs alone account for wave propagation.

PMID- 15143212
TI  - Connexins pave the way for vascular communication.
AB  - Coordinated behavior within arterioles is necessary for large resistance changes
      to occur and is reflected as a conduction of dilations/constrictions along
      arterioles. These responses arise from locally initiated hyper- or
      depolarizations that propagate via transmembrane channels formed by connexins
      (gap junctions). Mounting evidence indicates that gap-junctional communication
      contributes to the control of vascular tone.

PMID- 15143213
TI  - Cellular and gene therapy for major histocompatibility complex class II
      deficiency.
AB  - Major histocompatibility complex (MHC) class II deficiency is a primary
      immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model
      of this disease. In addition, by a direct genetic correction approach, a
      diagnostic test to determine which of the four MHC II genes is defective in new
      MHC II-deficiency patients has been optimized.

PMID- 15143214
TI  - NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that
      regulates B cell development and signaling.
AB  - A functional cDNA cloning system was developed by using a retrovirus library
      encoding CD8-chimeric proteins and a nuclear factor of activated T cells (NFAT)
      GFP reporter cell line to identify molecules inducing NFAT activation. By using
      this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor
      tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to
      the Ig superfamily and is predominantly expressed in spleen B and T cells. NFAM1
      crosslinking induced ITAM phosphorylation, ZAP-70/Syk recruitment, NFAT
      activation, and cytokine production. In vivo overexpression of NFAM1 in bone
      marrow chimeras and transgenic mice induced severe impairment of early B cell
      development in an ITAM-dependent manner. In NFAM1-expressing B cells, B cell
      antigen receptor stimulation induced NFAM1 translocation to lipid raft, and NFAM1
      co-crosslinking augmented B cell antigen receptor signaling. The results suggest
      that NFAM1 modulates B cell signaling through its ITAM, which regulates B cell
      development.

PMID- 15143215
TI  - A model for Ure2p prion filaments and other amyloids: the parallel superpleated
      beta-structure.
AB  - In its prion form, Ure2p, a regulator of nitrogen catabolism in Saccharomyces
      cerevisiae, polymerizes into filaments whereby its C-terminal regulatory domain
      is inactivated but retains its native fold. The filament has an amyloid fibril
      backbone formed by the Asn-rich, N-terminal, "prion" domain. The prion domain is
      also capable of forming fibrils when alone or when fused to other proteins. We
      have developed a model for the fibril that we call a parallel superpleated beta
      structure. In this model, the prion domain is divided into nine seven-residue
      segments, each with a four-residue strand and a three-residue turn, that zig-zag
      in a planar serpentine arrangement. Serpentines are stacked axially, in register,
      generating an array of parallel beta-sheets, with a small and potentially
      variable left-hand twist. The interior of the filament is mostly stabilized not
      by packing of apolar side chains but by H-bond networks generated by the stacking
      of Asn side chains: charged residues are excluded. The model is consistent with
      current biophysical, biochemical, and structural data (notably, mass-per-unit
      length measurements by scanning transmission electron microscopy that gave one
      subunit rise per 0.47 nm) and is readily adaptable to other amyloids, for
      instance the core of Sup35p filaments and glutamine expansions in huntingtin.

PMID- 15143216
TI  - Bedout: a possible end-Permian impact crater offshore of northwestern Australia.
AB  - The Bedout High, located on the northwestern continental margin of Australia, has
      emerged as a prime candidate for an end-Permian impact structure. Seismic
      imaging, gravity data, and the identification of melt rocks and impact breccias
      from drill cores located on top of Bedout are consistent with the presence of a
      buried impact crater. The impact breccias contain nearly pure silica glass
      (SiO2), fractured and shock-melted plagioclases, and spherulitic glass. The
      distribution of glass and shocked minerals over hundreds of meters of core
      material implies that a melt sheet is present. Available gravity and seismic data
      suggest that the Bedout High represents the central uplift of a crater similar in
      size to Chicxulub. A plagioclase separate from the Lagrange-1 exploration well
      has an Ar/Ar age of 250.1 +/- 4.5 million years. The location, size, and age of
      the Bedout crater can account for reported occurrences of impact debris in
      Permian-Triassic boundary sediments worldwide.

PMID- 15143217
TI  - Increasing ozone over the Atlantic Ocean.
AB  - Ship-borne ozone (O3) measurements over the Atlantic Ocean during the period from
      1977 to 2002 show that O3 trends in the northern mid-latitudes are small. In
      contrast, remarkably large O3 trends occur at low latitudes and in the Southern
      Hemisphere, where near-surface O3 has increased by up to a factor of 2. The
      likely cause is the substantial increase of anthropogenic emissions of nitrogen
      oxides (NOx) associated with energy use in Africa, which has added to NOx from
      biomass burning and natural sources.

PMID- 15143218
TI  - Regeneration of male germline stem cells by spermatogonial dedifferentiation in
      vivo.
AB  - Although the ability of engrafted stem cells to regenerate tissue has received
      much attention, the molecular mechanisms controlling regeneration are poorly
      understood. In the Drosophila male germline, local activation of the Janus kinase
      signal transducer and activator of transcription (Jak-STAT) pathway maintains
      stem cells; germline stem cells lacking Jak-STAT signaling differentiate into
      spermatogonia without self-renewal. By conditionally manipulating Jak-STAT
      signaling, we find that spermatogonia that have initiated differentiation and are
      undergoing limited mitotic (transit-amplifying) divisions can repopulate the
      niche and revert to stem cell identity. Thus, in the appropriate
      microenvironment, transit-amplifying cells dedifferentiate, becoming functional
      stem cells during tissue regeneration.

PMID- 15143219
TI  - CT angiography of intracranial aneurysms: a focus on postprocessing.
AB  - Computed tomographic (CT) angiography is a well-known tool for detection of
      intracranial aneurysms and the planning of therapeutic intervention. Despite a
      wealth of existing studies and an increase in image quality due to use of
      multisection CT and increasingly sophisticated postprocessing tools such as
      direct volume rendering, CT angiography has still not replaced digital
      subtraction angiography as the standard of reference for detection of
      intracranial aneurysms. One reason may be that CT angiography is still not a
      uniformly standardized method, particularly with regard to image postprocessing.
      Several methods for two- and three-dimensional visualization can be used:
      multiplanar reformation, maximum intensity projection, shaded surface display,
      and direct volume rendering. Pitfalls of CT angiography include lack of
      visibility of small arteries, difficulty differentiating the infundibular
      dilatation at the origin of an artery from an aneurysm, the kissing vessel
      artifact, demonstration of venous structures that can simulate aneurysms,
      inability to identify thrombosis and calcification on three-dimensional images,
      and beam hardening artifacts produced by aneurysm clips. Finally, an algorithm
      for the safe and useful application of CT angiography in patients with
      subarachnoid hemorrhage has been developed, which takes into account the varying
      quality of equipment and software at different imaging centers.

PMID- 15143220
TI  - Optimizing Doppler and color flow US: application to hepatic sonography.
AB  - In the imaging of patients with chronic liver disease or portal hypertension or
      who have undergone liver transplantation or surgery, accurate evaluation of the
      hepatic vasculature is usually necessary. Because Doppler ultrasonography (US) is
      capable of accurately characterizing the nature of flow within the major hepatic
      arteries and the portal and hepatic veins, it is widely used for imaging the
      liver vasculature. An informed choice of transducer and scanning techniques is
      important in the evaluation of the liver vasculature. In addition, there are a
      variety of operator-dependent technical parameters (eg, baseline, frame rate,
      wall filters, gain, velocity range, angle correction, gate size and position)
      that must be optimized when performing Doppler US of the liver. Changes in these
      parameters independently influence both the color and spectral components of the
      Doppler US examination; therefore, the parameters should be optimized separately
      for each patient. Failure to appropriately adjust these parameters may result in
      artifacts or misinterpretation of the study, which will frequently affect patient
      treatment. In contrast, knowledge of these operator-dependent parameters will
      permit optimization of the study and improve the overall utility of liver Doppler
      US.

PMID- 15143221
TI  - MR cholangiopancreatography: improved ductal distention with intravenous morphine
      administration.
AB  - Magnetic resonance (MR) cholangiopancreatography has proved a robust and
      noninvasive imaging modality for evaluating the biliary and pancreatic ducts
      without the use of ionizing radiation. Although MR cholangiopancreatography
      reliably depicts the main extrahepatic and intrahepatic bile ducts, it does not
      depict the segmental intrahepatic ducts unless they are dilated. The segmental
      ducts are difficult to visualize with MR cholangiopancreatography because of
      their small caliber and the limited spatial resolution and signal-to-noise ratio
      achievable with standard MR pulse sequences. However, visualization of the normal
      (ie, nondistended) biliary system is necessary for the evaluation of donor
      candidates for living related liver transplantation. Because of the prevalence of
      variant biliary anatomy, MR cholangiopancreatography is often used for
      preoperative evaluation of prospective liver donors. Intravenous morphine
      administered prior to MR cholangiopancreatography can improve image quality by
      causing the sphincter of Oddi to contract, which increases pressure in and
      distention of the biliary and pancreatic ducts. Morphine administration may also
      be particularly helpful for the evaluation of patients with primary sclerosing
      cholangitis, malignant neoplasms such as cholangiocarcinoma, or cystic and non
      organ-deforming benign pancreatic neoplasms.

PMID- 15143222
TI  - Cross-sectional imaging in Crohn disease.
AB  - The role of cross-sectional imaging in the diagnosis of Crohn disease has
      expanded with recent technologic advances in computed tomography (CT) and
      magnetic resonance (MR) imaging that allow rapid acquisition of high-resolution
      images of the intestines. To acquire images of diagnostic quality, administration
      of a fairly large amount of intraluminal contrast agent prior to examination and
      scanning with intravenous contrast material injection are necessary. Both CT and
      MR imaging are reported to have a sensitivity of over 95% for the detection of
      Crohn disease; however, they may not allow early diagnosis. Colonoscopy and
      conventional enteroclysis studies are indicated for patients with early-stage
      disease. At more advanced stages, CT and MR imaging can help identify and
      characterize pathologically altered bowel segments as well as extraluminal
      lesions (eg, fistulas, abscesses, fibrofatty proliferation, increased vascularity
      of the vasa recta, mesenteric lymphadenopathy). These modalities can also clearly
      depict inflammatory lesion activity and conditions that require elective
      gastrointestinal surgery, thereby aiding in treatment planning. In the clinical
      setting, CT is currently the imaging modality of choice at most institutions;
      however, it is expected that MR imaging will soon play a comparable role. CT or
      MR imaging should be included in a comprehensive evaluation of patients with
      Crohn disease, along with conventional imaging and clinical and laboratory tests.

PMID- 15143224
TI  - The inaccessible or undrainable abscess: how to drain it.
AB  - Percutaneous abscess drainage is a safe, effective, and widely used technique for
      the treatment of patients with abdominal or pelvic sepsis. The majority of
      abdominal and pelvic abscesses afford reasonably straightforward access and are
      amenable to percutaneous drainage. However, requests are occasionally received
      for drainage of abscesses or fluid collections that initially appear unsuitable
      for percutaneous drainage. Factors that render collections seemingly unsuitable
      for imaging-guided drainage include inaccessibility due to surrounding organs,
      difficult location, and thickened contents (eg, clotted blood, thick pus). Well
      established alternative approaches (eg, transgluteal, transvaginal, transrectal)
      can be used to facilitate drainage of deep-seated collections that are
      inaccessible via more traditional routes. Other factors that may improve the
      accessibility of collections include modifications in patient positioning or in
      the use of imaging hardware (eg, angling of the computed tomography scanner
      gantry). Use of these techniques and modifications can allow percutaneous
      drainage of less accessible intraabdominal abscesses, thus eliminating the need
      for laparotomy.

PMID- 15143223
TI  - Disproportionate fat stranding: a helpful CT sign in patients with acute
      abdominal pain.
AB  - Fat stranding adjacent to thickened bowel wall seen at computed tomography (CT)
      in patients with acute abdominal pain suggests an acute process of the
      gastrointestinal tract, but the differential diagnosis is wide. The authors
      observed "disproportionate" fat stranding (ie, stranding more severe than
      expected for the degree of bowel wall thickening present) and explored how this
      finding suggests a narrower differential diagnosis, one that is centered in the
      mesentery: diverticulitis, epiploic appendagitis, omental infarction, and
      appendicitis. The characteristic CT findings (in addition to fat stranding) of
      each of these entities often lead to a final diagnosis. Diverticulitis manifests
      with mild, smooth bowel wall thickening and no lymphadenopathy. Epiploic
      appendagitis manifests with central areas of high attenuation and a
      hyperattenuated rim, in addition to its characteristic location adjacent to the
      colon. In contrast, omental infarction is always centered in the omentum. The
      most specific finding of appendicitis is a dilated, fluid-filled appendix.
      Correct noninvasive diagnosis is important because treatment approaches for these
      conditions range from monitoring to surgery.

PMID- 15143225
TI  - Percutaneous imaging-guided abdominal and pelvic abscess drainage in children.
AB  - Percutaneous imaging-guided drainage is the first-line treatment for infected or
      symptomatic fluid collections in the abdomen and pelvis, in the absence of
      indications for immediate surgery. The technology and expertise needed to perform
      percutaneous abscess drainage are widely available and readily adapted for use in
      the pediatric population. Catheter insertion procedures include the trocar and
      Seldinger techniques. Imaging guidance for drainage is most commonly performed
      with ultrasonography (US), computed tomography, or US and fluoroscopy combined.
      Abscesses in locations that are difficult to access, such as those deep in the
      pelvis, subphrenic regions, or epigastric region, can be drained by using the
      appropriate approach-transrectal, transgluteal, intercostal, or transhepatic.
      Although the causes of abscesses in children differ slightly from those of
      abscesses in the adult population, the frequency of successful treatment with
      percutaneous abscess drainage in children is 85%-90%, similar to that in adults.
      With expertise in imaging-guided drainage techniques and the ability to adjust to
      the special needs of children, interventional radiologists can successfully drain
      most abscesses and obviate surgery. Successful adaptation of abscess drainage
      techniques for pediatric use requires attention to the specific needs of children
      with respect to sedation, dedicated resuscitation and monitoring equipment,
      avoidance of body heat loss, minimization of radiation doses, and greater
      involvement of family compared with that in adult practice.

PMID- 15143226
TI  - Congenital hepatic shunts.
AB  - Abnormal vascular connections within the hepatic parenchyma are occasionally seen
      at ultrasonography (US) and require further evaluation. The radiologic findings
      in 42 children with infantile hepatic hemangioma (n = 28), vascular malformations
      (n = 10), or infradiaphragmatic total anomalous pulmonary venous return (TAPVR)
      (n = 4) associated with congenital vascular shunting were retrospectively
      reviewed. Arteriovenous connections are seen in infantile hepatic hemangiomas and
      arteriovenous malformations and manifest with aortic tapering at the level of the
      celiac trunk, hepatic artery enlargement with a low resistivity index (RI), and
      increased flow velocities in the hepatic veins that may assume an arterialized
      spectral pattern in late-stage disease. Congenital arterioportal shunts
      demonstrate a low RI in the hepatic artery, hepatofugal arterialized flow in the
      portal vein, and rapid development of signs of portal hypertension. Portosystemic
      shunting may be intra- or extrahepatic. A pulsatile triphasic spectral pattern is
      seen in the portomesenteric venous system in children with portosystemic
      shunting, and macroscopic connections between the portal system and the hepatic
      veins are evident. Infradiaphragmatic TAPVR is associated with a tortuous vessel
      that parallels the aorta, ends at the intrahepatic left portal vein or the ductus
      venosus, and has hepatopetal flow. Familiarity with the US features of various
      congenital abnormal hepatic vascular connections will aid in diagnosis and
      treatment.

PMID- 15143227
TI  - Gadolinium-enhanced three-dimensional MR angiography of Takayasu arteritis.
AB  - Takayasu arteritis is a form of large vessel vasculitis with a possible
      autoimmune origin that may cause stenosis of the aorta and its major branches.
      Six types of Takayasu arteritis are recognized; the type depends on whether the
      ascending aorta, descending thoracic aorta, abdominal aorta, aortic
      cervicobrachial branches, or renal arteries are affected. The coronary and
      pulmonary arteries are also sometimes involved. Clinical features of the disease
      include diminished or absent pulses, claudication, hypertension, and mesenteric
      angina. Conventional angiography has been the standard imaging tool for diagnosis
      and evaluation of Takayasu arteritis, although it demonstrates only the lumen of
      the vessel. Less invasive cross-sectional methods such as computed tomographic
      angiography and, more recently, three-dimensional magnetic resonance (MR)
      angiography can effectively demonstrate thickening of the vessel wall, which may
      be the earliest manifestation of the disease, occurring before stenosis and
      dilatation. MR imaging in particular allows better soft-tissue differentiation
      and can show other signs of inflammation, including mural edema and increased
      mural vascularity. Other advantages of MR imaging are the lack of iodinated
      contrast material or ionizing radiation.

PMID- 15143228
TI  - Pitfalls, artifacts, and remedies in multi- detector row CT coronary angiography.
AB  - Coronary angiography is increasingly performed with multi-detector row computed
      tomography (CT) in the clinical setting. Successful use of this method, however,
      depends on the radiologist's knowledge of its potential pitfalls and familiarity
      with methods for minimizing or avoiding them. To identify artifacts and other
      pitfalls that commonly degrade image quality and that could result in
      misinterpretation, contrast-enhanced coronary angiograms acquired with a multi
      detector row CT scanner with four detector rows in 110 consecutive patients were
      analyzed. The problems identified were classified into four broad categories: (a)
      motion-related artifacts caused by cardiac, pulmonary, or other body motion; (b)
      beam-hardening effects caused by metallic implants, severe calcifications, or air
      bubbles in the pulmonary artery that obscured the underlying coronary vessel
      lumen; (c) structural artifacts produced by adjacent contrast material-filled
      structures and overlying vessels; and (d) artifacts that resulted from technical
      errors or limitations. The most frequently observed artifacts were those related
      to cardiac motion. The most effective methods for minimizing cardiac motion
      artifacts are (a) premedication with beta-blockers to maintain optimal heart rate
      during scanning and (b) optimal selection of the reconstruction window.

PMID- 15143229
TI  - Thoracic manifestations of Behcet disease at CT.
AB  - Behcet disease is a multisystemic and chronic inflammatory disorder of unknown
      cause that is characterized by recurrent oral and genital ulcerations, ocular
      manifestations, and additional clinical manifestations in multiple organ systems.
      Behcet disease involving the chest can manifest as a wide spectrum of
      abnormalities. Although conventional chest radiography is commonly used for
      initial assessment, spiral computed tomography can demonstrate the entire
      spectrum of thoracic manifestations of Behcet disease, including abnormalities of
      the vessel lumen and wall, perivascular tissues, lung parenchyma, pleura, and
      mediastinal structures. Aneurysms of the pulmonary arteries, with or without
      thrombosis, are a typical manifestation of Behcet disease. Other manifestations
      include thrombosis, vasculitis, hemorrhage, infarction, and inflammation.
      Familiarity with these manifestations can be useful in the diagnosis of Behcet
      disease, helping to determine the cause of symptoms in patients who present with
      hemoptysis and guide the choice of appropriate therapy.

PMID- 15143230
TI  - Cisterna chyli at routine abdominal MR imaging: a normal anatomic structure in
      the retrocrural space.
AB  - The cisterna chyli, a dilated lymphatic sac in the retrocrural space, represents
      the origin of the thoracic duct. It is seen in approximately half of
      lymphangiographic studies and 20% of autopsies. Highly fluid-sensitive magnetic
      resonance (MR) imaging sequences such as single-shot rapid acquisition with
      refocused echoes, which are currently used in many abdominal MR imaging
      protocols, frequently result in the depiction of this structure. The cisterna
      chyli was evident on abdominal MR images acquired in 30 (15%) of 200 consecutive
      patients who underwent MR imaging at the authors' institution between February
      and June 2002. Its appearance varied from that of a thick tube to that of a thin
      tube, parallel or converging tubes, tortuous tubes, a sausage-shaped fluid
      collection, a focal collection, or a focal plexus. Radiologists who perform MR
      imaging should be familiar with the various possible appearances of this normal
      anatomic structure so as not to mistake it for a pathologic entity.

PMID- 15143231
TI  - From the archives of the AFIP: pulmonary Langerhans cell histiocytosis.
AB  - Pulmonary Langerhans cell histiocytosis (PLCH) is an isolated form of Langerhans
      cell histiocytosis that primarily affects cigarette smokers. PLCH is
      characterized by peribronchiolar proliferation of Langerhans cell infiltrates
      that form stellate nodules. The nodular lesions frequently cavitate and form
      thick- and thin-walled cysts, which are thought to represent enlarged airway
      lumina. PLCH lesions display temporal microscopic heterogeneity, with progression
      from dense cellular nodules to apparently cavitary nodules to increasing degrees
      of fibrosis that may extend along alveolar walls. In advanced cases, fibrotic
      scars are surrounded by enlarged, distorted air spaces. Affected patients are
      typically young adults who often present with cough and dyspnea. The
      characteristic radiographic features of PLCH are bilateral nodular and
      reticulonodular areas of opacity that predominantly involve the upper and middle
      lung zones with relative sparing of the lung bases. High-resolution computed
      tomography (CT) shows nodules and cysts in the same distribution and allows a
      confident prospective diagnosis of PLCH in the appropriate clinical setting. In
      typical cases, a predominantly nodular pattern is seen on CT scans in early
      phases of the disease, whereas a cystic pattern predominates in later phases. The
      radiologic abnormalities may regress, resolve completely, become stable, or
      progress to advanced cystic changes. Treatment consists of smoking cessation, but
      corticosteroid therapy may be useful in selected patients. Chemotherapeutic
      agents and lung transplantation may be offered to patients with advanced disease.
      The prognosis of PLCH is variable with frequent regression, stabilization, or
      recurrence of disease that does not correlate with cessation or continuation of
      smoking.

PMID- 15143233
TI  - Soft-tissue cavernous hemangioma.

PMID- 15143232
TI  - Best cases from the AFIP: hemimegalencephaly.

PMID- 15143234
TI  - Bladder squamous cell carcinoma.

PMID- 15143235
TI  - Echinococcal cyst.

PMID- 15143237
TI  - AAPM/RSNA tutorial on equipment selection: PACS equipment overview: display
      systems.
AB  - Display systems are key components of the digital radiology department. Current
      display systems for medical imaging are based on cathode-ray tubes (CRTs) or
      active-matrix liquid crystal displays (AMLCDs). The CRT is a cathodoluminescent
      display: Light is generated by exciting a luminescent material with energetic
      electrons. AMLCDs are light-modulating devices that form the image in the screen
      by controlling the transparency of individual display pixels. Many image quality
      aspects of CRTs are determined by the way the pixel luminance is generated in the
      cathodoluminescent screen. The resolution properties of AMLCDs are much better
      than those of CRTs. In CRT devices, phosphor granularity and raster scanning
      patterns are the main components of spatial noise. In AMLCDs, the most notable
      feature of the noise characteristic is the subpixel structure of complex pixel
      designs used in medical displays. The small-spot contrast of CRTs is dominated
      mainly by veiling glare and reflections of ambient illumination. In addition to
      display reflectance, the contrast of medical AMLCDs is affected by crosstalk and
      by variations of the luminance at off-normal viewing angles.

PMID- 15143236
TI  - MR lymphangiography: imaging strategies to optimize the imaging of lymph nodes
      with ferumoxtran-10.
AB  - Detection of local or regional metastases to lymph nodes is clinically important
      in virtually any type of primary tumor. Current imaging techniques rely heavily
      on the size criterion for characterization of nodal disease. However, size can be
      an ineffective parameter for diagnosis of tumor spread to lymph nodes. Magnetic
      resonance (MR) imaging performed before and after administration of ferumoxtran
      10 is a promising technique for characterization of lymph nodes in patients with
      various primary tumors. Normal homogeneous uptake of ferumoxtran-10 in
      nonmetastatic nodes shortens the T2 and T2*, turning these nodes dark, whereas
      malignant nodes lack uptake and remain hyperintense. To optimize acquisition
      strategies, the following factors should be considered: the timing of contrast
      material-enhanced imaging, the section thickness, the imaging plane, and the
      imaging parameters for T2*-weighted sequences. In addition, MR imaging with
      ferumoxtran-10 allows presurgical mapping of lymph nodes and quantitative
      estimation of T2*.

PMID- 15143238
TI  - DICOM structured reporting: Part 1. Overview and characteristics.
AB  - Supplement 23 to Digital Imaging and Communications in Medicine (DICOM) is an
      introduction to the structured reporting (SR) classes, which are used for
      transmission and storage of clinical documents. The SR classes fully support both
      conventional free-text reports and structured information, thus enhancing the
      precision, clarity, and value of clinical documentation. In addition, the SR
      standard provides the capability to link text and other data to particular images
      or waveforms and to store the coordinates of findings. In other words, SR
      documents not only describe the specific features contained in images or
      waveforms but can also refer to any number of images or waveforms. Accordingly,
      SR bridges the traditional gap between imaging systems and information systems.
      Furthermore, SR plays an essential role in Integrating the Healthcare Enterprise
      by providing healthcare practitioners with an effective tool that encompasses a
      variety of clinical contexts. Harmonization of DICOM SR and the Health Level
      Seven clinical document architecture standard is under way.

PMID- 15143239
TI  - DICOM structured reporting: Part 2. Problems and challenges in implementation for
      PACS workstations.
AB  - Structured reporting (SR) was recently added to the Digital Imaging and
      Communications in Medicine (DICOM) standard to provide an efficient mechanism for
      the generation, distribution, and management of clinical reports. The main
      advantage of SR is the ability to link clinical documents with the referenced
      images for simultaneous retrieval and display. A generic SR toolkit that covers
      the different clinical reports used in today's healthcare enterprises was
      developed for picture archiving and communication system (PACS) workstations. The
      modules of the SR toolkit collaborate to automatically construct the DICOM SR
      files from the free-text input presented in hypertext markup language (HTML) by
      using the associated SR trees. The DICOM toolkit is reused for SR encoding and
      DICOM services. A setup module was required for creating both the standard and
      private SR templates used in different healthcare specialties. The SR manager
      transparently converts between the different SR document presentations, that is,
      DICOM SR files and HTML documents, to provide the end users with an easy-to-use
      toolkit. To evaluate and demonstrate the effectiveness of the SR toolkit in a
      pragmatic setting, the toolkit was integrated into PACS workstations.

PMID- 15143240
TI  - Perceived threats and real killers.

PMID- 15143241
TI  - National Institutes of Health. Paid consulting: good for the staff, not for the
      chiefs.

PMID- 15143242
TI  - National Institutes Of Health. Are scientists worth more than senators?

PMID- 15143244
TI  - Space science. Hubble alternative to the rescue?

PMID- 15143243
TI  - Occupational health. Beset by lawsuits, IBM blocks a study that used its data.

PMID- 15143245
TI  - Planetary science. Endurance has its rewards on Mars.

PMID- 15143246
TI  - Paleontology. Evidence of huge, deadly impact found off Australian coast?

PMID- 15143247
TI  - Molecular biology. Consortium tackles mouse regulome.

PMID- 15143248
TI  - Biomedical research. New NIH training grants open to foreign students.

PMID- 15143249
TI  - U.S. immigration. Groups urge easing of restrictions on visa policies affecting
      scientists.

PMID- 15143250
TI  - International cooperation. Priorities for rebuilding civilian Iraqi science.

PMID- 15143252
TI  - Meteorology. Storm-in-a-box forecasting.

PMID- 15143251
TI  - Research ethics. South Korean cloning team denies improprieties.

PMID- 15143253
TI  - Meteorology. No end yet to forecast advances.

PMID- 15143254
TI  - Planetary science. Skywatchers await the fleeting shadow of Venus.

PMID- 15143255
TI  - American Physical Society meeting. Once again, dark matter eludes a
      supersensitive trap.

PMID- 15143256
TI  - American Physical Society meeting. Solar flares reveal surprising recipe.

PMID- 15143257
TI  - American Physical Society meeting. Gravity withstands close-up scrutiny.

PMID- 15143258
TI  - Higher education. Reinventing Europe's universities.

PMID- 15143259
TI  - Higher education. Russian universities want their share of the research pie.

PMID- 15143260
TI  - Contaminated evidence.

PMID- 15143262
TI  - Humidity, ice, and nitric acid.

PMID- 15143261
TI  - The future of GM crops.

PMID- 15143263
TI  - Comment on "Origin of the superflock of cichlid fishes from Lake Victoria, East
      Africa".

PMID- 15143265
TI  - Public health. Public health risk from the avian H5N1 influenza epidemic.

PMID- 15143266
TI  - Biomedicine. Do airborne particles induce heritable mutations?

PMID- 15143267
TI  - Geochemistry. Life's chemical kitchen.

PMID- 15143268
TI  - Neuroscience. Controlling the ups and downs of synaptic strength.

PMID- 15143269
TI  - Chemistry. New insights into the structure of water with ultrafast probes.

PMID- 15143271
TI  - Planetary science. The giant impact formation of the Moon.

PMID- 15143270
TI  - Immunology. The bell tolls for phagosome maturation.

PMID- 15143272
TI  - Evolution. Retrospective: in memory of John Maynard Smith (1920-2004).

PMID- 15143273
TI  - Recombination of human mitochondrial DNA.

PMID- 15143274
TI  - Retrotransposon-induced mutations in grape skin color.

PMID- 15143276
TI  - Extra-large-pore zeolites with two-dimensional channels formed by 14 and 12
      rings.
AB  - Stable zeolites that have larger pore apertures and a three-dimensional pore
      topology are of interest because they could be used to adsorb larger molecules,
      particularly for application in oil refining. Several large-pore zeolitic
      materials with channels formed by openings of more than 12 rings are known, but
      all of them have a one-dimensional channel system that limits their use in
      catalysis. We report the synthesis and some characterizations of IM-12, a
      thermally stable germanium-containing zeolite that contains the first two
      dimensional channel system with extra-large pores formed by 14- and 12-ring
      channels.

PMID- 15143275
TI  - Continuous particle separation through deterministic lateral displacement.
AB  - We report on a microfluidic particle-separation device that makes use of the
      asymmetric bifurcation of laminar flow around obstacles. A particle chooses its
      path deterministically on the basis of its size. All particles of a given size
      follow equivalent migration paths, leading to high resolution. The microspheres
      of 0.8, 0.9, and 1.0 micrometers that were used to characterize the device were
      sorted in 40 seconds with a resolution of approximately 10 nanometers, which was
      better than the time and resolution of conventional flow techniques. Bacterial
      artificial chromosomes could be separated in 10 minutes with a resolution of
      approximately 12%.

PMID- 15143277
TI  - Preference for vibrational over translational energy in a gas-surface reaction.
AB  - State-resolved gas-surface reactivity measurements revealed that vibrational
      excitation of nu3 (the antisymmetric C-H stretch) activates methane dissociation
      more efficiently than does translational energy. Methane molecules in the
      vibrational ground state require 45 kilojoules per mole (kJ/mol) of translational
      energy to attain the same reactivity enhancement provided by 36 kJ/mol of nu3
      excitation. This result contradicts a key assumption underlying statistical
      theories of gas-surface reactivity and provides direct experimental evidence of
      the central role that vibrational energy can play in activating gas-surface
      reactions.

PMID- 15143278
TI  - Asphalt volcanism and chemosynthetic life in the Campeche Knolls, Gulf of Mexico.
AB  - In the Campeche Knolls, in the southern Gulf of Mexico, lava-like flows of
      solidified asphalt cover more than 1 square kilometer of the rim of a dissected
      salt dome at a depth of 3000 meters below sea level. Chemosynthetic tubeworms and
      bivalves colonize the sea floor near the asphalt, which chilled and contracted
      after discharge. The site also includes oil seeps, gas hydrate deposits, locally
      anoxic sediments, and slabs of authigenic carbonate. Asphalt volcanism creates a
      habitat for chemosynthetic life that may be widespread at great depth in the Gulf
      of Mexico.

PMID- 15143279
TI  - Enhanced open ocean storage of CO2 from shelf sea pumping.
AB  - Seasonal field observations show that the North Sea, a Northern European shelf
      sea, is highly efficient in pumping carbon dioxide from the atmosphere to the
      North Atlantic Ocean. The bottom topography-controlled stratification separates
      production and respiration processes in the North Sea, causing a carbon dioxide
      increase in the subsurface layer that is ultimately exported to the North
      Atlantic Ocean. Globally extrapolated, the net uptake of carbon dioxide by
      coastal and marginal seas is about 20% of the world ocean's uptake of
      anthropogenic carbon dioxide, thus enhancing substantially the open ocean carbon
      dioxide storage.

PMID- 15143280
TI  - Reduction of particulate air pollution lowers the risk of heritable mutations in
      mice.
AB  - Urban and industrial air pollution can cause elevated heritable mutation rates in
      birds and rodents. The relative importance of airborne particulate matter versus
      gas-phase substances in causing these genetic effects under ambient conditions
      has been unclear. Here we show that high-efficiency particulate-air (HEPA)
      filtration of ambient air significantly reduced heritable mutation rates at
      repetitive DNA loci in laboratory mice housed outdoors near a major highway and
      two integrated steel mills. These findings implicate exposure to airborne
      particulate matter as a principal factor contributing to elevated mutation rates
      in sentinel mice and add to accumulating evidence that air pollution may pose
      genetic risks to humans and wildlife.

PMID- 15143281
TI  - TAF1 activates transcription by phosphorylation of serine 33 in histone H2B.
AB  - Dynamic changes in chromatin structure, induced by posttranslational modification
      of histones, play a fundamental role in regulating eukaryotic transcription. Here
      we report that histone H2B is phosphorylated at evolutionarily conserved Ser33
      (H2B-S33) by the carboxyl-terminal kinase domain (CTK) of the Drosophila TFIID
      subunit TAF1. Phosphorylation of H2B-S33 at the promoter of the cell cycle
      regulatory gene string and the segmentation gene giant coincides with
      transcriptional activation. Elimination of TAF1 CTK activity in Drosophila cells
      and embryos reduces transcriptional activation and phosphorylation of H2B-S33.
      These data reveal that H2B-S33 is a physiological substrate for the TAF1 CTK and
      that H2B-S33 phosphorylation is essential for transcriptional activation events
      that promote cell cycle progression and development.

PMID- 15143282
TI  - Regulation of phagosome maturation by signals from toll-like receptors.
AB  - In higher metazoans, phagocytosis is essential in host defense against microbial
      pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells
      are delivered on a common route from phagosomes to lysosomes for degradation.
      Here, we found that activation of the Toll-like receptor (TLR) signaling pathway
      by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps
      including internalization and phagosome maturation. Phagocytosis of bacteria was
      impaired in the absence of TLR signaling. Two modes of phagosome maturation were
      observed, constitutive and inducible; their differential engagement depended on
      the ability of the cargo to trigger TLR signaling.

PMID- 15143283
TI  - Species interactions and the evolution of sex.
AB  - The Red Queen hypothesis posits that sex has evolved in response to the shifting
      adaptive landscape generated by the evolution of interacting species. Previous
      studies supporting the Red Queen hypothesis have considered a narrow region of
      parameter space and only a subset of ecological and genetic interactions. Here,
      we develop a population genetics model that circumscribes a broad array of
      ecological and genetic interactions among species and derive the first general
      analytical conditions for the impact of species interactions on the evolution of
      sex. Our results show that species interactions typically select against sex. We
      conclude that, although the Red Queen favors sex under certain circumstances, it
      alone does not account for the ubiquity of sex.

PMID- 15143284
TI  - Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic
      plasticity.
AB  - Activation of N-methyl-d-aspartate subtype glutamate receptors (NMDARs) is
      required for long-term potentiation (LTP) and long-term depression (LTD) of
      excitatory synaptic transmission at hippocampal CA1 synapses, the proposed
      cellular substrates of learning and memory. However, little is known about how
      activation of NMDARs leads to these two opposing forms of synaptic plasticity.
      Using hippocampal slice preparations, we showed that selectively blocking NMDARs
      that contain the NR2B subunit abolishes the induction of LTD but not LTP. In
      contrast, preferential inhibition of NR2A-containing NMDARs prevents the
      induction of LTP without affecting LTD production. These results demonstrate that
      distinct NMDAR subunits are critical factors that determine the polarity of
      synaptic plasticity.

PMID- 15143285
TI  - Exclusive consolidated memory phases in Drosophila.
AB  - Two types of consolidated memory have been described in Drosophila, anesthesia
      resistant memory (ARM), a shorter-lived form, and stabilized long-term memory
      (LTM). Until now, it has been thought that ARM and LTM coexist. On the contrary,
      we show that LTM formation leads to the extinction of ARM. Flies devoid of
      mushroom body vertical lobes cannot form LTM, but spaced conditioning can still
      erase their ARM, resulting in a remarkable situation: The more these flies are
      trained, the less they remember. We propose that ARM acts as a gating mechanism
      that ensures that LTM is formed only after repetitive and spaced training.

PMID- 15143286
TI  - Scale errors offer evidence for a perception-action dissociation early in life.
AB  - We report a perception-action dissociation in the behavior of normally developing
      young children. In adults and older children, the perception of an object and the
      organization of actions on it are seamlessly integrated. However, as documented
      here, 18- to 30-month-old children sometimes fail to use information about object
      size and make serious attempts to perform impossible actions on miniature
      objects. They try, for example, to sit in a dollhouse chair or to get into a
      small toy car. We interpret scale errors as reflecting problems with inhibitory
      control and with the integration of visual information for perception and action.

PMID- 15143289
TI  - Increased arterial stiffness is independently related to cerebrovascular disease
      and aneurysms of the abdominal aorta: the Second Manifestations of Arterial
      Disease (SMART) Study.
AB  - BACKGROUND: Arterial stiffness is a risk factor for stroke and myocardial
      infarction. We investigated whether carotid arterial stiffness is related to
      other localizations of manifest arterial disease. METHODS: Carotid artery
      stiffness was measured by ultrasonography as the change in diameter in systole
      relative to the diastolic diameter in patients enrolled in the Second
      Manifestations of Arterial Disease (SMART) Study, a cohort study among patients
      with manifest cardiovascular disease or cardiovascular risk factors. The first
      consecutive 1561 patients with manifest cardiovascular disease were classified in
      4 categories: cerebrovascular disease, coronary artery disease, peripheral artery
      disease, or aneurysm of the abdominal aorta (AAA). Differences in arterial
      stiffness among the categories were studied by linear regression analyses.
      Patients with coronary artery disease as single diagnosis (n=482) served as
      reference group. RESULTS: Patients with cerebrovascular disease (arterial
      distension -42.0 microm [95% CI, -57.2 to -26.8]) and those with an AAA (-64.4
      microm [95% CI, -84.8 to -44.0]) had an increased carotid stiffness compared with
      the reference group. Adjustment for confounders attenuated the relations, which
      remained statistically significant (-34.2 microm [95% CI, -47.8 to -20.7] and 
      33.2 microm [95% CI, -51.8 to -14.6], respectively). CONCLUSIONS: Our study
      suggests that increased arterial stiffness is important in the pathophysiology of
      especially cerebrovascular disease and AAA. That the differences in arterial
      stiffness between disease categories attenuated after adjustment for important
      risk factors but remained significant suggests that besides being an element in
      the causal pathway, arterial stiffness is also a risk factor for cardiovascular
      disease itself.

PMID- 15143288
TI  - Validation of the aphasic depression rating scale.
AB  - BACKGROUND AND PURPOSE: The Aphasic Depression Rating Scale (ADRS) was developed
      to detect and measure depression in aphasic patients during the subacute stage of
      stroke. METHODS: Six experts selected an initial sampling of behavioral items
      from existing depression rating scales. Stroke patients (aphasic and nonaphasic)
      were assessed with these items by the rehabilitation staff, with the Hamilton
      Depression Rating Scale (HDRS) for nonaphasic patients only, by a psychiatrist,
      and by the rehabilitation staff with Visual Analog Scales (VAS). A second item
      selection was conducted after a regression algorithm was run including VAS as
      independent variables (criterion validity) and after their factorial structure
      was analyzed with a principal component analysis (factorial validity). The
      construct validity was evaluated with respect to the other depression
      assessments. A threshold for the diagnosis of depression was computed with
      respect to the psychiatrist's diagnosis. Interrater and test-retest reliability
      were assessed in 2 additional groups of aphasic patients. RESULTS: Eighty
      patients participated in the study (59 aphasic). Fifteen behavioral items from
      existing depression rating scales were selected, and 9 were retained after the
      validation process. ADRS correlated highly with VAS and HDRS (r=0.60 to 0.78,
      P=10(-4) to 10(-6)). With respect to the psychiatrist's diagnosis, the
      sensitivity and specificity of ADRS were 0.83 and 0.71, respectively, when the
      threshold was set at 9/32. Its factorial structure was comparable to HDRS
      structure. Interrater and test-retest reliability were high (average kappa
      coefficient of the 9 items=0.69). CONCLUSIONS: ADRS is a valid, reliable,
      sensitive, and specific tool for the evaluation of depression in aphasic patients
      during the stroke subacute phase.

PMID- 15143290
TI  - Is elevated mean platelet volume associated with a worse outcome in patients with
      acute ischemic cerebrovascular events?
AB  - BACKGROUND AND PURPOSE: Increased mean platelet volume (MPV), indicating higher
      platelet reactivity, is associated with an increased risk of myocardial
      infarction. Higher levels of MPV have been found in patients with acute ischemic
      stroke than in control subjects. Data from smaller studies regarding an
      association between MPV and stroke severity and outcome have been controversial.
      If such an association exists, MPV might help to identify patients at increased
      risk of a severe course of acute cerebrovascular disease. METHODS: Within a
      multicenter, cross-sectional study nested in a cohort, we analyzed the relation
      between MPV and stroke severity as determined by the modified Rankin Scale after
      1 week in 776 patients with acute ischemic stroke or transient ischemic attack.
      By multivariate logistic regression modeling, we determined the influence of MPV
      on stroke severity, adjusting for potential confounding factors. RESULTS:
      Patients within the highest quintile of MPV had a significantly higher risk of
      suffering a severe stroke, defined as modified Rankin Scale score of 3 to 6,
      compared with patients within the lowest quintile (odds ratio=2.6; 95% confidence
      interval, 1.6 to 4.1; P<0.001). This association remained significant after
      adjustment for possible confounding factors (odds ratio=2.2; 95% confidence
      interval, 1.2 to 4.0; P=0.013). CONCLUSIONS: Our results indicate that an
      elevated MPV is associated with a worse outcome for acute ischemic
      cerebrovascular events independent of other clinical parameters.

PMID- 15143292
TI  - Sodium intake and risk of death from stroke in Japanese men and women.
AB  - BACKGROUND AND PURPOSE: Despite the evidence for a positive association of
      dietary salt and blood pressure, the few prospective studies that have assessed
      the association between dietary salt and stroke have reported inconsistent
      results. The purpose of this study was to examine the relation between sodium
      intake and death from stroke in a population-based cohort of Japanese men and
      women. METHODS: In 1992, usual diet including sodium intake was determined in 13
      355 men and 15 724 women in Takayama City, Gifu, with the use of a validated food
      frequency questionnaire. RESULTS: There were 269 stroke deaths (137 men and 132
      women) between baseline and 1999. In men, the highest compared with the lowest
      tertile of sodium intake was significantly positively associated with death from
      total stroke after controlling for covariates (hazard ratio [HR]), 2.33; 95% CI,
      1.23 to 4.45). Significantly positive associations were also observed between
      sodium intake and death from ischemic stroke (HR, 3.22; 95% CI, 1.22 to 8.53) as
      well as death from intracerebral hemorrhage (HR, 3.85; 95% CI, 1.16 to 12.7). A
      positive association between sodium intake and death from stroke in women was
      suggested, although the associations for total stroke and ischemic stroke were of
      borderline significance (HR, 1.70; 95% CI, 0.96 to 3.02 and HR, 2.10; 95% CI,
      0.96 to 4.62, respectively). CONCLUSIONS: These prospective data support the
      hypothesis that dietary salt increases the risk of death from stroke.

PMID- 15143293
TI  - Stroke care delivery in institutions participating in the Registry of the
      Canadian Stroke Network.
AB  - BACKGROUND AND PURPOSE: Guidelines and performance indicators have been
      established for acute stroke care. However, little is known about the process of
      stroke care delivery in Canada. METHODS: The Registry of the Canadian Stroke
      Network (RCSN) captured detailed clinical data on patients with stroke and
      transient ischemic attack seen at 21 acute care institutions across Canada. Data
      from phase 1 of the RCSN (June 2001 to February 2002) were used to determine the
      use of evidence-based acute stroke care interventions in participating
      institutions. RESULTS: Overall, 4439 patients were seen during the study time
      frame and 1701 (38%) consented to full data collection. Thirty-one percent
      received care on a stroke unit or from a mobile stroke team. Among patients with
      ischemic stroke, 7% received thrombolysis, 80% underwent carotid imaging, 89%
      received antithrombotic agents, and 54% of those with atrial fibrillation
      received warfarin. There were significant intersite variations in the delivery of
      all of these interventions except for the use of antithrombotic agents, and these
      persisted after adjustment for age, sex, stroke type, and other comorbid
      conditions. CONCLUSIONS: Patients in institutions participating in the RCSN
      received high-quality stroke care based on a number of performance measures.
      However, gaps exist in the provision of other elements of stroke care,
      particularly organized inpatient stroke care and warfarin for atrial
      fibrillation. Future research should explore explanations for these findings and
      focus on solutions to deficiencies in care.

PMID- 15143294
TI  - Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage
      model.
AB  - BACKGROUND AND PURPOSE: Mitogen-activated protein kinase (MAPK) has been shown to
      be involved in the pathogenesis of cerebral vasospasm after subarachnoid
      hemorrhage (SAH). In the present study we examined the role of Ras protein, an
      upstream regulator of MAPK, and the effects of the inhibitors of Ras
      farnesyltransferase (FTase), FTI-277 and FTase inhibitor I, on angiographic
      vasospasm and clinical evaluations. METHODS: Twenty-five dogs were randomly
      divided into 5 groups: control, SAH, SAH+dimethyl sulfoxide, SAH+FTI-277, and
      SAH+FTase inhibitor I. An established canine double-hemorrhage model of SAH was
      used by injecting autologous arterial blood into the cisterna magna on days 0 and
      2. Angiography was performed at days 0 and 7. Clinical behavior and the
      activation of Ras (GTP-Ras) and phosphorylated ERK1/2 of MAPK in the basilar
      arteries were examined. RESULTS: Severe vasospasm was obtained in the SAH and
      SAH+dimethyl sulfoxide dogs (42.5+/-2.5% and 38.9+/-2.4%, respectively). Enhanced
      GTP-Ras and phosphorylated ERK1/2 were observed in the spastic basilar arteries
      (P<0.05). Inhibitors of Ras FTase decreased GTP-Ras and phosphorylated ERK1/2,
      attenuated angiographic vasospasm, and improved appetite and activity scores.
      CONCLUSIONS: Ras contributes to cerebral vasospasm, and inhibitors of Ras FTase
      may have potential in the management of cerebral vasospasm.

PMID- 15143295
TI  - Osteoprotegerin and osteopontin are expressed at high concentrations within
      symptomatic carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to compare the concentration of
      osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand
      (RANKL), and osteopontin (OPN) in stable (asymptomatic) and unstable
      (symptomatic) carotid atherosclerosis. In addition, we were interested in the
      effect of angiotensin II blockade on the secretion of these proteins by unstable
      atherosclerosis. METHODS: Endarterectomy samples removed from patients with
      recent (within 6 weeks) or no previous focal neurological symptoms were assessed
      by immunohistochemistry, Western analysis, and explant culture. Concentrations of
      OPG, RANKL, and OPN were measured by mean optical density (MOD), densitometry of
      protein bands, and enzyme-linked immunosorbent assay of supernatants from explant
      culture, and compared between symptomatic and asymptomatic patients. RESULTS: The
      concentration of OPG and OPN within the proximal internal carotid (PIC) part of
      the endarterectomy specimen removed from symptomatic patients was elevated 2- and
      4-fold, respectively. Although the concentration of RANKL did not differ
      according to patients' symptoms, the quantity of OPG secreted by explants of the
      PIC was greater in explants from symptomatic patients and could be significantly
      reduced within 48 hours of incubation with the angiotensin II blocker irbesartan.
      CONCLUSIONS: OPG and OPN are upregulated in symptomatic human carotid
      atherosclerosis with possible implications for plaque stability. Angiotensin II
      blockade is able to downregulate OPG secretion in vitro.

PMID- 15143296
TI  - Ischemic stroke in young women: a nested case-control study using the UK General
      Practice Research Database.
AB  - BACKGROUND AND PURPOSE: Estimates of the incidence of ischemic stroke in young
      women vary widely from 0.9 to 8.9 per 100,000 per year. This study was conducted
      to determine the incidence and risk factors for ischemic stroke in young women in
      the UK. METHODS: Women aged 15 to 49 with a first diagnosis and supporting
      evidence of ischemic stroke between January 1, 1992, and December 31, 1998, were
      identified from the UK General Practice Research Database. Age-specific incidence
      rates were calculated and a nested case-control study was conducted with up to 6
      controls randomly selected and matched to each case by year of birth and general
      practice. Crude and adjusted odds ratios (ORs) were calculated using conditional
      logistic regression. RESULTS: The incidence of ischemic stroke was 3.56/100 000
      per year. Factors associated with an increased risk were heart disease (OR,
      10.5), heavy alcohol consumption (OR, 8.5), previous venous thromboembolism (OR,
      6.2), treated diabetes mellitus (OR, 4.7), hypertension (OR, 4.6), migraine (OR,
      2.3), and use of combined oral contraceptives (OR, 2.3). Light alcohol
      consumption was found to be protective (OR, 0.17). CONCLUSIONS: The crude
      incidence rate was lower than previously reported for the USA and Europe but
      higher than that reported for the UK Oxford Region. This could be because of an
      under-representation of mild cases or because of a true lower incidence in the UK
      compared with the USA and the rest of Europe. The results of the case-control
      study are consistent with previous studies of ischemic stroke in young women.

PMID- 15143297
TI  - Angiotensin II AT1 receptor blockade reverses pathological hypertrophy and
      inflammation in brain microvessels of spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: The spontaneously hypertensive rat (SHR) is vulnerable to
      brain ischemia and stress and exhibits a chronically stimulated brain angiotensin
      II system, cerebrovascular hypertrophy, and inflammation. Pretreatment with
      angiotensin II type 1 (AT1) receptor antagonists protects from brain ischemia and
      from stress and prevents the development of stress-induced gastric ulcers in part
      by reducing inflammation in the gastric mucosa. We studied whether AT1 receptor
      antagonists could exert antiinflammatory effects in the brain vasculature as a
      mechanism for their protective effects against ischemia. METHODS: Ten-week-old
      SHR and normotensive Wistar-Kyoto male rats received the AT1 receptor antagonist
      candesartan (0.3 mg/kg per day) or vehicle for 28 days via osmotic minipumps. We
      studied AT1 receptors, intercellular adhesion molecule-1 (ICAM-1), endothelial
      nitric oxide synthase (eNOS), and number of macrophages by immunohistochemistry
      and Western blots. RESULTS: We found increased endothelial AT1 receptor
      expression of brain microvessels and middle cerebral artery of SHR. Brain AT1
      receptor inhibition reversed the pathological vascular hypertrophy, increased and
      normalized eNOS expression, and decreased ICAM-1 expression and the number of
      adherent and infiltrating macrophages in cerebral vessels of SHR. CONCLUSIONS:
      The antiinflammatory effects of AT1 receptor antagonists may be an important
      mechanism in protecting against ischemia.

PMID- 15143298
TI  - Insidious cognitive decline in CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks
      leading to subcortical vascular dementia. The aim of this study was to
      characterize cognitive function in subjects with a C475T (R133C) mutation in the
      Notch3 gene, leading to CADASIL. METHODS: Prestroke (n=13) and poststroke (n=13)
      mutation carriers and mutation carriers with dementia (n=8) were compared with
      healthy noncarriers from the same families using a comprehensive set of
      neuropsychological tests. RESULTS: Changes in working memory and executive
      function were observed in the very early phase of the disease before transient
      ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive
      impairment concerned also mental speed and visuospatial ability. Finally, the
      subjects with dementia had multiple cognitive deficits, which engaged even verbal
      functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups
      without dementia and the controls could be reliably distinguished using 3 tests
      that assessed working memory/attention, executive function, and mental speed.
      Episodic memory was relatively well-preserved late in the disease. CONCLUSIONS: A
      deterioration of working memory and executive function was already observed in
      the prestroke phase, which means that cognitive decline may start insidiously
      before the first onset of symptomatic ischemic episodes.

PMID- 15143300
TI  - Cerebrovascular mortality 10 years after stroke: a population-based study.
AB  - OBJECTIVES: Cerebrovascular mortality has declined in the general population of
      Sweden. The objective of the present study was to investigate causes of death
      among stroke patients in a long-term perspective. RESEARCH DESIGN AND METHODS: A
      population-based study was conducted of first-ever strokes in the municipality of
      Soderhamn, Sweden. Standardized mortality ratios were calculated for comparison
      with the general population. Three time periods (1975 to 1978, 1983 to 1986, and
      1987 to 1990) were analyzed. All 1186 patients were followed up for at least 10
      years. RESULTS: Cerebrovascular mortality was greatly increased (more than 10
      fold) in comparison with the general population during all study periods. The
      mortality from ischemic heart disease and some other diseases was moderately
      raised (3- to 8-fold), whereas the mortality from malignant disorders was normal.
      CONCLUSIONS: Cerebrovascular disease was the predominant cause of death among
      Swedish stroke patients in the 1970s and the 1980s.

PMID- 15143299
TI  - Genetic variation in white matter hyperintensity volume in the Framingham Study.
AB  - BACKGROUND AND PURPOSE: In a previous study of normal elderly male twins, the
      heritability of quantitative white matter hyperintensity (WMH) volume has been
      estimated to be high (0.73). We investigated heritability of WMH in a family
      based sample of the Framingham Heart Study for sex differences and the impact of
      age. METHODS: Brain magnetic resonance scans were performed on 2012 individuals
      in the cohort and offspring of the Framingham study. This report was limited to
      1330 stroke-free and dementia-free members (mean age 61.0 years) of the
      Framingham offspring. Individuals with a history of multiple sclerosis, stroke,
      dementia, or other neurological condition including traumatic brain injury were
      excluded from this analysis. WMH volume and total cranial volume (TCV) were
      quantified using a previously published algorithm. Because of extreme skewing,
      measures of WMH were log-transformed before analysis. Variance components methods
      were used to estimate heritability of WMH after adjusting for sex, age, age2, and
      TCV. RESULTS: In the full dataset, WMH heritability was 0.55 (P<0.0001).
      Heritability among women was 0.78 (P<0.0001) whereas heritability among men was
      0.52 (P<0.0003). Heritability varied as average age increased, with a peak of
      0.68 (P<0.0001) in individuals aged 55 or older. CONCLUSIONS: Using a family
      based study design comprising generally healthy individuals, this study found
      high heritability of WMH overall and similar heritability for both men and women.
      In addition, the heritability of WMH remained high among individuals in whom the
      prevalence of cerebrovascular brain injury was generally low, suggesting that WMH
      is also likely to be an excellent genetic marker of brain aging.

PMID- 15143301
TI  - Direct thrombin inhibition: a novel approach to stroke prevention in patients
      with atrial fibrillation.

PMID- 15143303
TI  - [Heart-lung interactions].

PMID- 15143304
TI  - [Pulmonary hypertension and peripheral edema in COPD].

PMID- 15143305
TI  - [Pulmonary artery hypertension and the obstructive sleep apnea syndrome].

PMID- 15143306
TI  - [Diagnostic and treatment of pulmonary embolism related acute pulmonary artery
      hypertension].

PMID- 15143308
TI  - [The contribution of Doppler-echocardiography to the diagnosis of a left heart
      cause of dyspnea].

PMID- 15143307
TI  - [Pulmonary artery hypertension: therapeutic progress].

PMID- 15143309
TI  - [Left heart failure and coronary artery disease in COPD].

PMID- 15143310
TI  - [Cardiac sarcoidosis].

PMID- 15143311
TI  - [Cardiac asthma].

PMID- 15143312
TI  - [Cardiovascular complications of the obstructive apnea-hypopnea syndrome: the
      effects of continuous positive airway pressure].

PMID- 15143313
TI  - [Cardiovascular side effects of drugs used in respiratory diseases].

PMID- 15143314
TI  - [Iatrogenic respiratory complications of cardiovascular drugs].

PMID- 15143315
TI  - [Heart-lung interactions: applications to respiratory disease].

PMID- 15143316
TI  - Advanced sequencing technologies: methods and goals.

PMID- 15143317
TI  - An assessment of the sequence gaps: unfinished business in a finished human
      genome.

PMID- 15143318
TI  - Improving the efficiency of RNA interference in mammals.

PMID- 15143319
TI  - Resurrecting ancient genes: experimental analysis of extinct molecules.

PMID- 15143320
TI  - Time to draw breath: asthma-susceptibility genes are identified.

PMID- 15143321
TI  - Micromanagers of gene expression: the potentially widespread influence of
      metazoan microRNAs.

PMID- 15143334
TI  - Protein overexpression and gene amplification of HER-2 and EGFR in colorectal
      cancers: an immunohistochemical and fluorescent in situ hybridization study.
AB  - Overexpression of HER-2 and the epidermal growth factor receptor (EGFR) has been
      observed in many cancers, sometimes accompanied by gene amplification. To assess
      whether novel chemotherapies targeting these overexpressed proteins may be
      effective for the treatment of colorectal cancers, we examined the exact
      frequency of HER-2 and EGFR overexpression, the relationship between gene
      amplification and protein expression, and the heterogeneity of gene amplification
      within and between primary and metastatic tumors. We evaluated 244 colorectal
      cancers immunohistochemically. All tumors found to overexpress HER-2 or EGFR were
      further analyzed for gene amplification by fluorescent in situ DNA hybridization.
      Overexpression of HER-2 and EGFR was found in 8 (3%) and 19 (8%) of the 244
      colorectal carcinomas, respectively. Gene amplification was observed in 100 and
      58% of the tumors exhibiting HER-2 and EGFR overexpression, respectively. HER-2
      amplification in cancer cells was characterized by clusters of hybridization
      signals, suggesting amplicons in homogeneously staining regions that were
      predominant in most primary and metastatic tumors. EGFR amplification, observed
      as scattered signals reminiscent of amplicons in double minute chromosomes, or
      coamplification of EGFR with the centromeric regions was observed as a minor
      population within primary tumors, and found in variety of populations in
      metastatic tumors. Overexpression of HER-2 and EGFR were observed in only a small
      fraction of colorectal carcinomas, but were frequently accompanied by gene
      amplification.

PMID- 15143335
TI  - Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and
      related glandular lesions: a possible link between lobular endocervical glandular
      hyperplasia/pyloric gland metaplasia and 'adenoma malignum'.
AB  - Gastrointestinal phenotype in cervical adenocarcinomas was examined by
      immunohistochemistry and correlated with morphologic features. Antibody panels
      included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition,
      expression of p16INK4, a cyclin-dependent kinase inhibitor which is expressed in
      a variety of high-risk HPV-related conditions, was studied. A total of 94
      invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs)
      and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently
      positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate
      of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85%
      whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were
      positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and
      MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs,
      indicating incomplete intestinal differentiation without a brush border in most
      of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates
      of 60% and 62%, respectively. Nuclear and cytoplasmic p16INK4 positivity was
      identified in 93% of UEAs, whereas 30% of MDAs were positive for p16INK4. Results
      in AISs were comparable to their invasive counterparts, but morphologically usual
      type AISs identified in eight cases of MDA were frequently positive for HIK1083
      (75%) and MUC6 (63%), and p16INK4. Of note was the existence of lobular
      endocervical glandular hyperplasia (LEGH) with atypical features including
      cytologic abnormalities, and/or papillary projection, which were identified in
      this study in pure form (n=3) or in association with MDAs (n=6), but not in cases
      of other types of adenocarcinomas. These observations indicate that
      gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there
      seems to be a possible link between MDA, and LEGH and morphologically usual-type
      AIS with gastric immunophenotype in histogenesis. Frequent absence of p16INK4
      expression in MDAs suggests a possibility that high-risk HPV does not play a
      crucial role in development of MDAs, in contrast to the majority of endocervical
      adenocarcinomas. p16INK4 immunohistochemistry appears to be a promising
      diagnostic tool, but pathologists should be aware of frequent negative staining
      in MDAs, which can be a source of erroneous diagnosis.

PMID- 15143336
TI  - Unusual tumors associated with the hereditary nonpolyposis colorectal cancer
      syndrome.
AB  - The molecular pathogenesis of tumors outside the usual tumor spectrum for
      hereditary nonpolyposis colorectal cancer (HNPCC) is currently controversial.
      Specifically, it is not known whether these tumors are related to defects in DNA
      mismatch repair or arise independently of this defect in these patients. Here, we
      report two young patients, each with a known MSH2 mutation in the family, who
      developed rare tumors (adrenal cortical carcinoma and anaplastic carcinoma of the
      thyroid) that are not usually associated with HNPCC. Both of these patients were
      members of families that fulfilled modified Amsterdam (Amsterdam II) criteria for
      this familial cancer syndrome. Both the adrenal tumor and the thyroid tumor
      showed complete loss of immunohistochemical expression for MSH2 protein. Neither
      tumor was considered microsatellite instability-high following microsatellite
      instability analysis using the established National Cancer Institute panel of
      five microsatellite markers. To our knowledge, MSH2 defects in these types of
      tumors have not been previously reported in patients with the HNPCC syndrome. Our
      results suggest that microsatellite instability analysis using the National
      Cancer Institute panel of five microsatellite markers may not detect
      microsatellite instability in tumors that fall outside the usual tumor spectrum
      of this syndrome. Therefore, when analyzing unusual tumors in patients with known
      or suspected HNPCC syndrome, we advocate the performance of immunohistochemistry
      for mismatch repair gene products in addition to microsatellite instability
      analysis.

PMID- 15143338
TI  - Infantile hemangiomas are arrested in an early developmental vascular
      differentiation state.
AB  - Infantile hemangiomas, the most common tumors of infancy, are vascular tumors
      characterized by rapid proliferation of endothelial cells during the first few
      months of postnatal life followed by slow spontaneous involution, whose molecular
      pathogenesis remains unclear. The recent identification of developmental
      expression of vascular lineage-specific markers prompted us to characterize
      infantile hemangiomas for the expression of lymphatic endothelial hyaluronan
      receptor-1 (LYVE-1), Prox-1, CD31 and CD34. We found that LYVE-1, a specific
      marker for normal and tumor-associated lymphatic vessels, was strongly expressed
      in tumor cells of infantile hemangiomas (n=28), but not in other vascular tumors
      including pyogenic granulomas (n=19, P<0.0001) or intramuscular hemangiomas
      (n=9), using LYVE-1/CD31 double immunostains. Whereas LYVE-1 expression was
      detected on the endothelial cells of all proliferating infantile hemangiomas,
      this lymphatic marker was absent from the lesional capillaries during involution
      in the majority of cases (P=0.0009). The majority of LYVE-1(+) endothelial cells
      also expressed CD34, but were negative for the lymphatic-specific homeobox
      protein Prox-1. Based on coexpression of both LYVE-1 and the blood vascular
      marker CD34, we propose that the endothelial cells in proliferating infantile
      hemangioma are arrested in an early developmental stage of vascular
      differentiation. The immature, incompletely differentiated immunophenotype of
      proliferating infantile hemangiomas may contribute to their rapid growth during
      the first few months of life.

PMID- 15143337
TI  - Expression of Birt-Hogg-Dube gene mRNA in normal and neoplastic human tissues.
AB  - Birt-Hogg-Dube (BHD) syndrome is an inherited autosomal genodermatosis
      characterized by hamartomas of the hair follicle called fibrofolliculomas and an
      increased risk for developing spontaneous pneumothorax, lung cysts and renal
      neoplasia. BHD was localized to chromosome 17p11.2 by linkage analysis in BHD
      families, and germline insertion/deletion and nonsense mutations in a novel gene
      were identified which were predicted to prematurely truncate the BHD protein,
      folliculin. No homology to other human proteins was found although folliculin was
      conserved across species. As a first step toward understanding the function of
      BHD in the cell and how BHD mutations can lead to the BHD phenotype, we measured
      the expression of BHD mRNA in normal and neoplastic human tissues by fluorescent
      in situ hybridization. BHD mRNA was expressed in a variety of tissues, including
      the skin and its appendages, the distal nephron of the kidney, stromal cells and
      type 1 pneumocytes of the lung, acinar cells of the pancreas and parotid gland,
      and epithelial ducts of the breast and prostate. In the brain, BHD mRNA was
      expressed in neurons of the cerebrum, and Purkinje cells in the cerebellum. BHD
      mRNA was also expressed in macrophage and lymphocytes in the tonsils and spleen.
      Tissues with reduced expression of BHD mRNA included heart, muscle and liver. BHD
      mRNA was expressed strongly in the proliferating epithelial strands of
      fibrofolliculomas, the cutaneous lesions characteristic of BHD, but not in renal
      tumors from BHD patients. These results indicate a wide expression pattern for
      BHD mRNA in many tissues, including skin, lung and kidney, which are involved in
      the BHD phenotype, and support a tumor suppressor role for BHD in renal cancer.

PMID- 15143339
TI  - The site of infection and ethnicity of the patient influence the biological
      pathways to HPV-induced mucosal cancer.
AB  - High-risk human papillomaviruses are the causative agents of cervical cancer and
      are also believed to be aetiologically involved in a subset of squamous cell
      carcinomas of the head and neck region, especially the tonsil. Cervical cancers
      arise through disruption of the pathways of p53 and the product of the
      retinoblastoma gene by the human papillomavirus oncoproteins E6 and E7. It is
      generally assumed that the same pathways are involved in human papillomavirus
      induced carcinogenesis at other mucosal surfaces. However, the patterns of
      expression of cell cycle proteins targeted by human papillomavirus E6 and E7 in
      cancers from different anatomic sites have been inconsistent, due to either
      biologic or technological factors. In this study, 73 human papillomavirus, 16
      positive cervical squamous cell carcinomas (35 from Australian and 38 from
      Chinese women) were analysed for the expression of p53, pRb, p16(INK4A),
      p21(CIP1/WAF1), p27(KIP1) and cyclin D1 by semiquantitative immunohistochemistry.
      Cervical cancers from Chinese women were found to be significantly more likely to
      overexpress p53, pRb, p21 and p27 than their Australian counterparts. These
      findings were compared with those from 31 human papillomavirus 16-positive
      tonsillar squamous cell carcinomas, all of Australian origin, tested using the
      same methodology. Comparisons of the tonsillar and combined cervical data showed
      that tonsillar cancers were significantly more likely to be p53-positive, whereas
      cervical cancers were significantly more likely to overexpress pRb, p16 and p27.
      When the tonsillar data were compared with cervical data from Australian women,
      the associations for p53 and pRb remained. These findings represent new evidence
      that the molecular pathways to human papillomavirus-induced mucosal cancer may be
      influenced by anatomic location and ethnicity.

PMID- 15143340
TI  - Intravascular bone marrow accumulation in persistent polyclonal lymphocytosis: a
      misleading feature for B-cell neoplasm.
AB  - Persistent polyclonal B-cell lymphocytosis is usually reported in young smoking
      women. Whether this syndrome represents a premalignant or benign disease remains
      unclear. Indeed, because of the association of Bcl-2/IgH rearrangement and
      cytogenetic abnormalities, such cases may be misdiagnosed as the leukemic phase
      of a non-Hodgkin's lymphoma. We report eight new cases of persistent polyclonal B
      cell lymphocytosis, which displayed a misleading bone marrow histological
      pattern, that is, intravascular B-cell infiltrate, constantly associated with Bcl
      2 immunohistostaining, as seen in some lymphoma. We also show the absence or low
      expression of adhesion molecules on persistent polyclonal B-cell lymphocytes,
      suggesting that migration abnormalities might lead to bone marrow and peripheral
      blood accumulation. Although most cases presented multiple Bcl-2/IgH gene
      rearrangements and appeared to be polyclonal, oligoclonal expansion was
      identified in one out of eight patients, yet was not associated with clinical
      aggressiveness. The occasional reports of oligoclonal IgH and Bcl-2/IgH
      rearrangements in this disorder suggest that polyclonal expansion may be followed
      by the emergence of a predominant clone. However, the benign clinical course and
      lack of biological evolution in most cases imply that it is mandatory to
      distinguish this disorder from other malignant lymphoproliferations, so that
      unnecessary aggressive therapy can be avoided.

PMID- 15143341
TI  - t(1;14) and t(11;18) in the differential diagnosis of Waldenstrom's
      macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia is caused by several B-cell proliferative
      disorders including lymphoplasmacytic lymphoma, marginal zone B-cell lymphoma, B
      cell chronic lymphocytic leukemia and multiple myeloma. Differential diagnosis
      between lymphoplasmacytic lymphoma and extranodal marginal zone lymphoma of
      mucosa-associated lymphoid tissue is particularly difficult as there is a
      considerable overlap in histological presentation. We report a case of
      Waldenstrom's macroglobulinemia with involvement of the peripheral blood, bone
      marrow and stomach. Serum chemistry revealed an IgM of 5.4 g/dl, but Bence-Jones
      protein in urine was negative. Abnormal lymphoid cells were detected in both
      blood and the bone marrow. Flow cytometry of the bone marrow aspirate showed that
      majority of cells were CD20(+), CD38(+), expressing immunoglobulin lambda light
      chain, but CD5(-) and CD10(-). Gastric biopsies revealed infiltration of the
      gastric mucosa by small lymphoid cells showing plasmacytoid differentiation and
      occasional Dutcher bodies. Lymphoepithelial lesions and Helicobacter pylori were
      not seen. Thus, the differential diagnosis between lymphoplasmacytic lymphoma and
      mucosa-associated lymphoid tissue lymphoma was raised. To resolve this, we
      performed BCL10 immunohistochemistry and reverse transcriptional polymerase chain
      reaction (RT-PCR) for the API2-MALT1 fusion transcript of t(11;18)(q21;q21). Both
      bone marrow and gastric biopsies showed strong BCL10 nuclear staining, similar to
      that seen in t(1;14)(p22;q32) positive mucosa-associated lymphoid tissue
      lymphoma, but absence of the API2-MALT1 fusion transcript. To further ascertain
      whether the detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) can be reliably
      used for the differential diagnosis between lymphoplasmacytic lymphoma and mucosa
      associated lymphoid tissue lymphoma, we screened for these translocations by
      BCL10 immunohistochemistry in 58 lymphoplasmacytic lymphomas and RT-PCR for
      t(11;18)(q21;q21) in 40 lymphoplasmacytic lymphomas, respectively. None of the
      lymphoplasmacytic lymphomas studied harbored these translocations. Thus,
      detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) is useful in the differential
      diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid
      tissue lymphoma.

PMID- 15143342
TI  - Functional conservation of interactions between a homeodomain cofactor and a
      mammalian FTZ-F1 homologue.
AB  - Nuclear receptors are master regulators of metazoan gene expression with crucial
      roles during development and in adult physiology. Fushi tarazu factor 1 (FTZ-F1)
      subfamily members are ancient orphan receptors with homologues from Drosophila to
      human that regulate diverse gene expression programs important for developmental
      processes, reproduction and cholesterol homeostasis in an apparently ligand
      independent manner. Thus, developmental and tissue-specific cofactors may be
      particularly important in modulating the transcriptional activities of FTZ-F1
      receptors. In Drosophila, the homeodomain protein Fushi tarazu acts as a cofactor
      for FTZ-F1 (NR5A3), leading to the hypothesis that a similar type of homeodomain
      cofactor-nuclear receptor relationship might exist in vertebrates. In this study,
      we have identified and characterized the homeodomain protein Prox1 as a co
      repressor for liver receptor homologue 1 (LRH1/NR5A2), a master regulator of
      cholesterol homeostasis in mammals. Our study suggests that interactions between
      LRH1 and Prox1 may fulfil roles both during development of the enterohepatic
      system and in adult physiology of the liver.

PMID- 15143343
TI  - Following single antibody binding to purple membranes in real time.
AB  - Antibody binding to surface antigens in membranes is the primary event in the
      specific immune defence of vertebrates. Here we used force microscopy to study
      the dynamics of antibody recognition of mutant purple membranes from
      Halobacterium salinarum containing a genetically appended anti-Sendai recognition
      epitope. Ligation of individual anti-Sendai antibodies to their antigenic
      epitopes was observed over time. Their increase in number within a small selected
      area revealed an apparent kinetic on-rate. The membrane-bound antibodies showed
      many different conformations that ranged from globular to V- and Y-like shapes.
      The maximum distance of two Fab fragments of the same antibody was observed to be
      approximately 18 nm, indicating an overall strong intrinsic flexibility of the
      antibody hinge region. Fab fragments of bound anti-Sendai antibodies were
      allocated to antigenic sites of the purple membrane, allowing the identification
      and localization of individual recognition epitopes on the surface of purple
      membranes.

PMID- 15143345
TI  - Analysis of the horseradish peroxidase/indole-3-acetic acid combination in a
      three-dimensional tumor model.
AB  - Horseradish peroxidase has previously been shown to catalyze the conversion of
      indole-3-acetic acid (IAA) to a potent cytotoxin in a gene therapy setting. A
      three-dimensional spheroid model composed of a human head and neck carcinoma cell
      line, has been used to mimic the tumor microenvironment, such as regions of
      hypoxia. Exposure of intact spheroids to 0.05-5 mM concentrations of IAA and the
      halogenated indole, 5-bromoindole-3-acetic acid (5Br-IAA), resulted in decreased
      cell survival, and demonstrates that this combination is effective under tumor
      simulated conditions. In addition, 5Br-IAA, displayed selectivity for spheroids
      with a large hypoxic fraction following short exposure times.

PMID- 15143344
TI  - Chemoattractant-induced Ras activation during Dictyostelium aggregation.
AB  - Ras proteins are highly conserved molecular switches that regulate cellular
      response to external stimuli. Dictyostelium discoideum contains an extensive
      family of Ras proteins that function in regulation of mitosis, cytoskeletal
      function and motility, and the onset of development. Little is known about the
      events that lead to the activation of Ras proteins in Dictyostelium, primarily
      owing to a lack of a biochemical assay to measure the levels of activated Ras. We
      have adapted an assay, used successfully to measure activated Ras in mammalian
      cells, to monitor activation of two Dictyostelium Ras proteins, RasC and RasG. We
      have found that the Ras-binding domain (RBD) of mammalian Raf1 was capable of
      binding to the activated form of RasG, but not to the activated form of RasC;
      however, the RBD of Schizosaccharomyces pombe Byr2 was capable of binding
      preferentially to the activated forms of both RasC and RasG. Using this assay, we
      discovered that RasC and RasG showed a rapid and transient activation when
      aggregation-competent cells were stimulated with the chemoattractant cAMP, and
      this activation did not occur in a number of cAMP signalling mutants. These data
      provide further evidence of a role for both RasC and RasG in the early
      development of Dictyostelium.

PMID- 15143346
TI  - Omomyc expression in skin prevents Myc-induced papillomatosis.
AB  - Obligate sensitization to apoptosis provides a safeguard mechanism against the
      oncogenic potential of Myc. Omomyc is a mutant bHLHZip domain that sequesters Myc
      in complexes that are unable to bind to the E box recognition element and
      activate transcription but remain competent for transcriptional repression.
      Omomyc has the peculiar properties of reverting Myc-induced transformation of
      tissue culture cells and enhancing Myc proapoptotic function. Thus, Omomyc has
      the potential to act as a potent suppressor of Myc-induced oncogenesis. To
      validate the therapeutic potential of Omomyc in vivo, we targeted its expression
      to the adult suprabasal epidermis of Inv-c-MycER (TAM) transgenic mice which
      express a switchable form of the Myc protein in suprabasal cells. Activation of
      Myc induces rapid epidermal hyperplasia and papillomatosis. We show that Omomyc
      inhibits such Myc-induced papillomatosis, potentiating Myc-dependent apoptosis in
      a tissue in which it is usually strongly suppressed. Furthermore, Omomyc
      expression restores the normal keratinocyte differentiation program and skin
      architecture, both of which are otherwise disrupted by Myc activation. These
      findings indicate that it is possible to selectively enhance the intrinsic
      apoptotic pathway mediated by Myc and so quell its oncogenic action.

PMID- 15143348
TI  - Autophagy in human tumors: cell survival or death?

PMID- 15143347
TI  - Apoptosis and plaque destabilization in atherosclerosis: the role of macrophage
      apoptosis induced by cholesterol.

PMID- 15143349
TI  - HIV: no PUMA no death?

PMID- 15143350
TI  - I1 imidazoline receptor-mediated effects on apoptotic processes in PC12 cells.

PMID- 15143351
TI  - Early work on the role of mitochondria in apoptosis, an interview with Guido
      Kroemer.

PMID- 15143353
TI  - One-day primary care morbidity surveys: a feasible means for obtaining valuable
      healthcare services data.

PMID- 15143352
TI  - Early work on the function of CD95, an interview with Shige Nagata.

PMID- 15143354
TI  - John Hunter (1728 - 1793): founder of scientific surgery.

PMID- 15143355
TI  - 2001 survey on primary medical care in Singapore.
AB  - INTRODUCTION: The 2001 survey on primary medical care was undertaken to compare
      updated primary healthcare practices such as workload and working hours in the
      public and private sectors; determine private and public sector market shares in
      primary medical care provision; and gather the biographical profile and morbidity
      profile of patients seeking primary medical care from both sectors in Singapore.
      This is the third survey in its series, the earlier two having been carried out
      in 1988 and 1993, respectively. METHODS: The survey questionnaire was sent out to
      all the 1480 family doctors in private primary health outpatient practice, the 89
      community-based paediatricians in the private sector who were registered with the
      Singapore Medical Council and also to all 152 family doctors working in the
      public sector primary medical care clinics. The latter comprised the polyclinics
      under the two health clusters in Singapore, namely the Singapore Health Services
      and National Healthcare Group, and to a very much smaller extent, the School
      Health Service's (SHS) outpatient clinics. The survey was conducted on 21 August
      2001, and repeated on 25 September 2001 to enable those who had not responded to
      the original survey date to participate. Subjects consisted of all outpatients
      who sought treatment at the private family practice clinics (including the
      clinics of the community-based paediatricians), and the public sector primary
      medical care clinics, on the survey day. RESULTS: The response rate from the
      family doctors in private practice was 36 percent. Owing to the structured
      administrative organisation of the polyclinics and SHS outpatient clinics, all
      returns were completed and submitted to the respective headquarters. Response
      from the community-based paediatricians was poor, so their findings were omitted
      in the survey analysis. The survey showed that the average daily patient-load of
      a family doctor in private practice was 33 patients per day, which was lower than
      the 40 patients a day recorded in 1993. The average working hours of each of
      these private practitioners was 7.6 hours per day. Family doctors in public
      sector primary medical care clinics were responsible for 16.6 percent of the
      patient-load for primary medical care in Singapore while the remaining 83.4
      percent was provided by family doctors in private practice. Singaporeans made
      approximately 4.4 visits to a family doctor in 2001, which was lower than the 5.0
      visits ascertained in 1993. Chronic medical conditions seen by family doctors as
      a whole, increased from 29.2 percent in 1993 to 34.3 percent in 2001. Upper
      respiratory tract infections and hypertension were the two leading disease
      conditions seen at both private and public sector primary medical care clinics in
      2001. The load of hypertension managed at primary medical care clinics had
      notably increased. CONCLUSION: The public sector share of outpatient load at 17
      percent in 2001 is well within the 25 percent level set in the Government's 1993
      White Paper on Affordable Healthcare. The private sector remains the main
      provider of primary medical care in Singapore, serving 83 percent of the
      population. The average workload for each family doctor in private practice had
      dropped from 40 to 33 patients a day between 1993 and 2001. There had been a
      notable growth in family doctors working in the private sector over this period.
      Both sectors saw an increase in the chronic disease load that they managed.

PMID- 15143356
TI  - Using pulsed-field gel electrophoresis in the molecular investigation of an
      outbreak of Serratia marcescens infection in an intensive care unit.
AB  - INTRODUCTION: Serratia marcescens is a well-known cause of nosocomial infections
      and outbreaks, particularly in immunocompromised patients with severe underlying
      disease. An outbreak due to S. marcescens infection was detected from 13 to 22
      February 2001 at the intensive care unit (ICU) of our institution. We used pulsed
      field gel electrophoresis (PFGE) typing to analyse the outbreak strains involved.
      METHODS: A total of 25 isolates were included in this study: 12 isolates from
      infected patients, nine isolates from insulin solution, one isolate from sedative
      solution (midazolam and morphine infusion) and one isolate from frusemide
      solution. Two isolates from other wards which were epidemiologically-unrelated
      were also included. RESULTS: The S. marcescens from patients, insulin solution
      and sedative solution showed an identical PFGE fingerprint pattern. The isolate
      from the frusemide solution had a closely-related PFGE pattern to the outbreak
      strain with one band difference. Attempts were made in the present study to
      identify the environmental reservoir of S. marcescens during the outbreak. We
      found that the insulin and sedative solutions used by the patients were
      contaminated with S. marcescens which was proven to be the source of the
      outbreak. CONCLUSION: Using PFGE, we showed that the outbreak in the ICU of our
      hospital was due to the clonal spread of a single strain of S. marcescens.

PMID- 15143358
TI  - Rhinosporidiosis: an unusual cause of nasal masses gains prominence.
AB  - INTRODUCTION: Rhinosporidiosis is a rare cause of nasal masses locally, with only
      two cases reported over a 35-year period. METHODS: Four patients with
      rhinosporidiosis, all from the Indian subcontinent, were managed at our tertiary
      referral centre over a recent five-year period. They presented with nasal masses
      and the diagnosis was confirmed by histological examination. RESULTS: All
      patients were treated by local excision of the nasal masses, and two also
      received dapsone therapy after surgery. During follow-up, local recurrence was
      found in two patients, one of whom had received dapsone. CONCLUSION: With a
      significant number of foreign workers from endemic regions, this uncommon disease
      may be observed more frequently in the future. It is thus important to consider
      the diagnosis of rhinosporidiosis in patients from endemic regions presenting
      with nasal masses. The mainstay of treatment should be wide surgical excision.

PMID- 15143357
TI  - Therapeutic plasmapheresis for the treatment of the thrombotic thrombocytopenic
      purpura-haemolytic uraemic syndromes.
AB  - INTRODUCTION: The thrombotic thrombocytopenic purpura-haemolytic uraemic
      syndromes (TTP-HUS) are uncommon disorders that are fatal if untreated.
      Therapeutic plasma exchange has resulted in excellent remission and survival
      rates in this patient population. METHODS: We reviewed our experience of
      therapeutic plasmapheresis for TTP-HUS syndromes for 11 patients who presented in
      the last five years. Parameters captured included haemoglobin and platelet counts
      at presentation as well as the number of plasmapheresis sessions and adjunctive
      treatment given. RESULTS: We found a response rate of 82 percent to plasma
      exchange, of whom 55 percent attained complete remission. Responses were
      excellent in the five patients who presented with primary or idiopathic TTP (100
      percent response) among whom 80 percent had sustained long term responses.
      Responses were poor and often unsustained (only one out of six survived) in
      patients who presented with thrombotic microangiopathies secondary to underlying
      disorders such as bone marrow transplantation and metastatic carcinoma.
      CONCLUSION: Plasmapheresis is mandatory and extremely effective for primary TTP.
      However, it is at most an adjunct for patients who developed it secondary to an
      underlying disorder until and if the primary disorder can be successfully
      treated.

PMID- 15143359
TI  - Importation of seven cases of an unusual helminthic infection into Singapore and
      assessment of the risk of local transmission.
AB  - Singapore remains vulnerable to the introduction of infectious diseases from
      other countries due to the high traffic of migrant labour and other visitors. We
      describe seven cases of migrant workers from West Africa who entered Singapore
      carrying loaisis, a helminthic infection. The clinical presentation, treatment
      using single dose ivermectin, potential for transmission, and the need for
      screening of this infection in Singapore are discussed.

PMID- 15143360
TI  - Piriformis pyomyositis: a rare cause of sciatica.
AB  - A 30-year-old Thai woman with piriformis pyomyositis presented with sciatica.
      Computed tomography showed swelling and enhancement of the right gluteus medius
      and piriformis muscles. She made a complete recovery after a course of
      intravenous antibiotics. This condition has only been reported three other times
      and is often diagnosed with difficulty. It could be erroneously dismissed as a
      lumbar disc prolapse. If untreated, it could lead to prolonged hospital stay and
      death. A high index of suspicion, early diagnosis and appropriate antibiotic or
      surgical treatment leads to full recovery.

PMID- 15143361
TI  - Role of non-invasive ventilation in difficult-to-wean children with acute
      neuromuscular disease.
AB  - Weaning from mechanical ventilation in children could be time-consuming and on
      many occasions, leads to reintubation with its associate complications. We report
      two children with acute neuromuscular disease, in whom bi-level positive airway
      pressure (BiPAP) as a mode of non-invasive ventilation was successfully used to
      wean the child from ventilators and prevented the need for tracheostomy. Despite
      the limited number of studies published in the literature suggesting BiPAP as a
      mode of weaning from mechanical ventilation, the technique when applied correctly
      seems to be safe and effective in weaning and avoiding tracheostomy.

PMID- 15143362
TI  - Non-traumatic acute paraplegia caused by cervical disc herniation in a patient
      with sleep apnoea.
AB  - A 57-year-old man with obstructive sleep apnoea presented with acute progression
      of myelopathy into paraplegia resulting from cervical disc herniation at C4-C5
      and C5-C6 levels. There was no associated history of trauma. Rapid progress to
      paraplegia from non-traumatic cervical disc herniation rarely occurs. Diagnostic
      and treatment modalities are discussed. The possible relationship between
      cervical myelopathy and sleep apnoea is also discussed.

PMID- 15143363
TI  - Clinics in diagnostic imaging (97). Right renal tuberculous autonephrectomy.
AB  - A 50-year-old man presented with recurrent episodes of right flank pain and
      dysuria for many years. Abdominal radiograph and intravenous urography showed
      extensive right renal parenchymal calcification in a lobar distribution and a non
      functioning right kidney, characteristic of end-stage tuberculosis. The
      pathology, clinical manifestations, and radiological findings of renal
      tuberculosis are discussed.

PMID- 15143366
TI  - [Epidemiological features of bronchial carcinoma cases with environmental
      asbestos exposure].
AB  - Due to environmental asbestos exposure, asbestos related lung diseases are common
      in Eskisehir district of Anatolia. In this study we aimed both to determine the
      epidemiological findings of the patients diagnosed as bronchial carcinoma and to
      discuss the features, which were probably related to asbestos exposure, presented
      by the patients. From May 1997 to December 2000, 301 cases were included in the
      study. Of the patients, 97 (32.2%) had epidermoid cell type, 84 (27.9%) had small
      cell, 39 (13%) had adenocarcinoma, 4 (1.3%) had large cell. Adenocarcinomas were
      more frequent in women. There were not significant differences among the cell
      types from the point of view of the age distributions. Adenocarcinomas were more
      frequently located in lower lobes of the lungs (36.9%) and more frequently showed
      peripheral locations (45.9%) than other cell types (20.6% for epidermoid and
      14.6% for small cell). Pleural effusion was more detected in adenocarcinomas
      (48.7% to 17.3% in epidermoid, 18.3% in small cell). The duration of smoking was
      shortest in adenocarcinomas, mean 32.4 years; the same duration was 56.2 years
      for epidermoid carcinomas. Of the patients, 54% had asbestos exposure.
      Adenocarcinomas were more frequently detected in the patients who exposed to
      asbestos but did not smoke. Our findings support that asbestos exposure may
      increase adenocancer frequency. The epidemiological and clinical features of
      adenocancer cases exposed to asbestos environmentally were not different than
      those of adenocancer cases exposed to asbestos occupationally.

PMID- 15143367
TI  - [The correlation between the distant metastases and organ-specific symptoms in
      the patients with lung cancer].
AB  - In this study, the correlation between distant metastases and metastatic organ
      specific abnormalities in patients with lung cancer was evaluated. There were 197
      patients who have lung cancer with distant metastases in this study. 141 (71.5%)
      of them were nonsmall cell lung cancer and 56 (28.5%) of them were small cell
      lung cancer. While one site of liver, brain and bone metastases were detected in
      128 (64.9%) patients, remainders (69 patients, 35.1%) had surrenal, renal,
      pancreatic, skin, lung, thyroid, abdominal lymph node metastases. Organ-specific
      symptoms, findings on physical examination and abnormalities in laboratory data
      were detected in 121 (56.5%), 45 (21%) and 52 (24.2 %) patients, respectively.
      Sensitivity of predilection of organ-specific symptoms for bone, liver and brain
      metastases were 67%, 43% and 74% and specificity were 86%, 90% and 76%,
      respectively. We concluded that organ-specific abnormalities were not so
      effective to predict metastases in lung cancer. We considered that this result
      could be due to retrospective analysis and not included enough patients.

PMID- 15143368
TI  - Immunoglobulins and complement components in patients with lung cancer.
AB  - Based on data providing a correlation between immunoglobulin or complement
      components levels and malignancies and specific disease parameters, we examined
      the possible correlation between the immunoglobulins, complement component levels
      and the stage of disease and the survival of patients. Sera from 55 patients with
      lung cancer and 22 healthy donor were assayed in order to evaluate the
      concentration of IgG, IgA, IgM, IgE, C3, C4. No considerable differences were
      found between the levels of immunoglobulins in patients with carcinoma of the
      lung versus subjects in the control group. Complement components (C3 and C4)
      levels were elevated in cancer patients with different cell types compared with
      levels in the control group. No statistically significant differences were found
      between the levels of the studied parameters and the stage of the disease and the
      survival time of patients. Our study confirm the hypothesis that malignant
      tumours contribute to elevation of complement components levels but additional
      studies are needed for demonstrating the prognostic value of immunoglobulin and
      complement components levels in lung cancer patients.

PMID- 15143369
TI  - [Correlation of serum IgE levels with severity of acute pulmonary
      thromboembolism].
AB  - We aimed to investigate whether there is a direct correlation of serum IgE
      concentration with severity of acute pulmonary thromboembolism (PTE). DESIGN:
      Prospective study. SETTINGS: University medical center. Forty-six patients (27
      female, 19 male) who were diagnosed as acute PTE in our clinic between 01 October
      2000 and 30 November 2001 comprised the study group. Mean age was 55 (range was
      20-82). The study group was divided into three groups according to severity of
      PTE: Group A, submassive PTE without pulmonary infarction (20 patients); group B,
      submassive PTE with pulmonary infarction (15 patients); and group C, massive PTE
      (11 patients). Serum IgE concentrations were measured by ELISA method at 1st,
      5th, 15th, 30th, 60th, 90th days, and 120th days, if needed, after the diagnosis.
      Statistical analysis was made by Post hoc Tukey test. First day serum IgE levels
      were highest in group B (mean 507.7) followed by group C (mean 324.2), and were
      lowest in group A (mean 117.2). The differences between group B and group C,
      between group B and group A, and also between group C and A were all
      statistically significant (p< 0.5, p< 0.0001, p< 0.015, respectively). 5th day
      and 15th day results showed statistically significant differences between group B
      and A, and between group C and A (at 5th day: p<0.0001, p< 0.015 respectively,
      and at 15th day: p< 0.0001, p< 0.012 respectively). At 30th, 60th, and 90th days
      of diagnosis serum IgE concentrations were higher in group B than in group A
      which were statistically significant (p< 0.0001, p< 0.0001, p< 0.019
      respectively). Patients with submassive PTE and pulmonary infarction had the
      highest serum IgE concentrations and the longest duration of high levels of IgE.

PMID- 15143370
TI  - [The influence of sarcoidosis on quality of life].
AB  - In the follow up of chronic illnesses like sarcoidosis, the psychological and
      social dimensions are getting more important in addition to the clinical
      parameters. It is the quality of life (QoL) that brings psychological and social
      dimensions in to the clinic. In this study we aimed to investigate the QoL of
      patients suffering from sarcoidosis. Study Short Form (SF-36) QoL scala was
      applied to 70 sarcoidosis patients who have been followed up in our center at
      least for a year. Among these patients 49 were females, 21 were males and the
      mean age was 43.27 +/- 11.97, mean disease duration was 3.55 +/- 1.80 (1-8
      years). In our study, we found that variables belonging to sarcoidosis influence
      the QoL as well as the patient herself/himself. While age and female gender
      influenced almost all parameters of QoL, in cases with symptoms physical
      component had been influenced most. Diffusing capacity (DLCO) showed positive
      correlation with many of the parameters of QoL, whereas disease stage did
      negative. Patients' income and their to be treatment did not affect QoL. In
      conclusion, we suggest that QoL may help to follow up and decide on the treatment
      of sarcoidosis along with the other treatment criteria.

PMID- 15143371
TI  - [The role of high resolution computerized tomography (HRCT) in the diagnosis and
      treatment of pulmonary tuberculosis].
AB  - In this study we have tried to put forth the role of thorax high resolution
      computerized tomography (HRCT) in the pursue of the diagnosis and treatment of
      pulmonary tuberculosis. It was detected that of the 67 patients with active
      tuberculosis, 66 (98.5%) had centrilobular nodule or branching linear structures,
      65 (97%) had acinary nodule, 55 (82%) had consolidation, 55 (82%) had cavities,
      54 (80.5%) had tree in bud appearance and 52 (77.6%) were bilateral. Of 30
      patients suffering from inactive tuberculosis, 26 (86.6%) were detected to have
      fibrotic changes, 20 (66.6%) bronchiectasis, 18 (60%) bronchovascular distortion
      and 14 (46.6%) pericicatrial emphysema. The sensitivity, specificity, positive
      predictive value, negative predictive values of thorax HRCT in determining the
      activity of the illness were found as 97%, 86.7%, 94.2% and 92.9% respectively.
      In conclusion we can say that thorax HRCT is a powerful and reliable diagnostic
      method for pulmonary tuberculosis. Thorax HRCT can be used as noninvasive
      diagnostic method especially in the patients suffering from smear and culture
      negative active tuberculosis.

PMID- 15143372
TI  - [BCG vaccination: where are we now?].
AB  - The bacillus Calmette-Guerin (BCG) vaccine is administered and recommended for
      the prevention and control of tuberculosis in developing countries with high-risk
      settings. A new general BCG vaccination programme against tuberculosis has been
      introduced since 1997 in Turkey. The aim of this study was to evaluate the BCG
      vaccination status in Duzce and to analyze contributing factors for the
      vaccination programme. BCG screening were performed in 1100 8th class students
      from nine primary schools of Duzce city centre and seven counties. BCG scar
      presence was taken as authoritative for vaccination status. BCG vaccination ratio
      was 0.94. Of 1100 students, 1030 had BCG scars; 478 had single scar, 536 had two
      scars and 16 had three scars. The significant negative correlation was observed
      between the BCG administration ratio and the number of children under age of 15
      per health personnel (r= -0.771, p= 0.025). Furthermore, based on some published
      studies marked regional variation of BCG vaccination status in Turkey was also
      discussed in this article.

PMID- 15143373
TI  - [The effect of comorbidity on prognosis in patients with COPD].
AB  - Patients with chronic obstructive pulmonary disease (COPD) have an increased risk
      of death from causes other than COPD. A study was undertaken to identify the most
      common comorbid diseases and to assess prognostic role of comorbidity in COPD. A
      cohort of 406 COPD patients, mean (+/- SD) 64 +/- 9 years were evaluated. Age,
      sex, smoking history, FEV1, comorbid conditions were recorded. Follow-up was
      conducted by means of telephone calls. Logistic regression analysis was used to
      identify the independent predictors of death. The mean (+/- SD) FEV1 was 1.40 +/-
      0.58 L. The most common comorbid diseases were hypertension (22%), coronary heart
      disease (8.9%), diabetes mellitus (7.4%), cancer (6.4%), heart failure (4.9%) and
      cerebrovascular disease (2%). The median follow-up was (+/- SD) 21 +/- 11 months.
      Twenty-four (5.9%) patients died during the follow-up period. Deaths from COPD
      were associated with FEV1 [RR 0.143 (95% CI 0.75-1.21)], heart failure (RR 0.177)
      and cancer (RR 0.064). In conclusion; while the most common comorbid diseases in
      COPD were hypertension, coronary heart disease and diabetes mellitus; FEV1, heart
      failure and cancer were associated factors with increased risk of death from
      COPD.

PMID- 15143374
TI  - [Completion pneumonectomy: indications, complications, and results].
AB  - Completion pneumonectomy is reported to be associated with high morbidity and
      mortality, especially when performed in patients with benign diseases. In our
      study we aimed to evaluate all patients underwent completion pneumonectomy in our
      clinic and to compare indications, complications and postoperative results with
      the literatures. Between January 1987 and December 2001, 27 consecutive patients
      who underwent completion pneumonectomy in our clinic were retrospectively
      reviewed. Postoperative morbidity and mortality rates were calculated according
      to indications and the results were compared to the standard pneumonectomies.
      There were 27 patients, 13 (48.1%) women and 14 (51.9%) men, with a median age of
      26 (range, 10 to 62 years). Completion pneumonectomy was performed for benign
      diseases in 23 (85.2%) patients and for malign diseases in 4 (14.8%). Malign
      indications included 2 second primary tumors and 2 local recurrences. In the
      group with benign diseases; completion pneumonectomy was performed for
      tuberculosis in 5, bronchiectasis in 14, bronchopleural fistula in 2 and necrosis
      of lung in 2. Hospital mortality was 7.4% including 1 intraoperative and 1
      postoperative deaths and both of them had undergone completion pneumonectomy for
      benign diseases. Complications occurred in 9 (33.3 %) patients, bronchopleural
      fistula + empyema were seen in 6 patients, cardiac rhythm disorders in 2 and
      wound infection in 1. All complications occurred in the patients operated for
      benign indications (39.1%). Completion pneumonectomy can be performed with an
      acceptable morbidity and mortality (similar to standard pneumonectomy) in
      selected cases. But the complication risk is higher in benign diseases,
      especially in tuberculosis. Surgical technique is important to avoid serious
      complications such as bronchopleural fistula and empyema.

PMID- 15143376
TI  - [The evaluation of Outpatient Smoking Cessation Clinic results].
AB  - Cigarette smoking is an intractable public health problem and health care
      providers play a important role in the effort to reduce the prevalence of
      smoking. Our outpatient smoking cessation clinic started working in April 2000.
      Since then it has been servicing once a week by appointment. After smoking habits
      and sociodemographic features of the people were asked all individuals attended a
      suitable smoking cessation program. The results were analyzed with Chi-square
      test and Kaplan Meier survival analysis. It was observed that 226 people, 97
      (42.9%) women and 129 (57.1%) men, visited the polyclinic during this period. The
      average age was 37.8 +/- 11.8 years. The rate of the smoking cessation was 43.4%
      at the end of the year. There were no relations between smoking cessation and
      initial age (p= 0.677), duration of smoking (p= 0.367), number of daily cigarette
      (p= 0.712), and nicotine addiction level (p= 0.673) and education level (p=
      0.131). We think that our results are important to show the importance of
      professional support in stopping smoking.

PMID- 15143375
TI  - [One-year follow up results of Smoking Cessation Outpatient Clinic].
AB  - In this study we investigated the five-year-results of our smoking cessation
      outpatient clinic retrospectively. Out of 839 subjects admitted to our clinic
      during this time period 634 of them completed the one-year follow up period. 318
      (50.2%) of these subjects were male and 316 (49.8%) of them were female. Subjects
      were divided into two groups. While one group received nicotine patch therapy,
      education and motivation the other group received just education and motivation.
      Mean age was 43.5 +/- 12 years. Nicotine patch therapy administered to 297
      subjects and smoking cessation rates in this group were 46.8% at 15th day and
      33.6% at the end of first year. The other group had smoking cessation rates of
      11.8% at 15th day and 10.9% at the end of one year. Out of 185 subjects who did
      not smoke at the end of 15th day 98 of them were also not smoking at the end of
      one year. 449 subjects were smoking at the end of 15th day and just 26 (5.7%) of
      them gave up smoking at the end of first year. Therapy compliance was 82.2% at
      the 15th day and 23.2% at 12th week. Most frequent side effects were local skin
      reactions (13.8%) due to nicotine patches, irritability and nervousness (8.5%)
      and concentration difficulties (7.4%). In this retrospective analysis we
      concluded that nicotine replacement therapy in conjunction with education and
      motivation may be an effective method for helping individuals in giving up
      smoking. We also observed that smoking situation in first 15 days is a good
      predictor of long-term success.

PMID- 15143377
TI  - [Three-dimensional computed tomography in acquired pediatric airway diseases].
AB  - To investigate the role of three-dimensional computed tomography (CT) in
      pediatric tracheobronchial diseases. Eleven male, six female patients aged from
      two weeks to 12 years (mean age, 3.3 years) were referred to spiral CT with a
      preliminary diagnosis of foreign body aspiration, extrinsic airway compression,
      acquired tracheoesophageal fistula, post-intubation stenosis, and bronchial
      erosion by a cavitary lung lesion. Tracheobronchial tree was scanned with 3 mm
      collimation, 1.5/1 pitch, 1.5 mm reconstruction interval, and standard
      reconstruction algorithm. Surface-rendered three-dimensional images and virtual
      bronchoscopic images were created from the axial raw data. Three-dimensional and
      virtual bronchoscopy findings were compared with findings of bronchoscopy.
      Virtual bronchoscopy revealed the level of obstruction in five patients with
      foreign body aspiration, but failed to disclose the nature of the aspirated
      foreign body and distinguish between a foreign body and mucoid obstruction.
      Virtual bronchoscopy correctly ruled out foreign body aspiration in four
      patients. Axial CT images also showed extraluminal findings including
      atelectasis, air trapping, peribronchial thickening, and infiltrations. In a
      patient with tracheitis virtual bronchoscopy failed to identify necrotic plaques
      observed in bronchoscopy. In patients with extrinsic compression, three
      dimensional images showed the site and degrees of stenosis, whereas axial images
      revealed the cause of compression. In one patient, an anomalous tracheal bronchus
      was demonstrated on three-dimensional and virtual bronchoscopy images. Three
      dimensional CT can localize tracheobronchial obstructions accurately. Virtual
      images may eliminate the need for invasive bronchoscopy in patients with
      questionable foreign body aspiration. Inability to evaluate the mucosal changes
      remains an important disadvantage of this technique.

PMID- 15143379
TI  - [Acute oxygen treatment].
AB  - Oxygen treatment is commonly used in clinical practice. Although this treatment
      was taught during medical education under different titles, it is observed that
      doctors do not administer oxygen treatment in adequate periods and doses. The
      possible cause of this may be that oxygen is not considered as a drug. The
      results of inadequate dose and insufficient monitoring in oxygen treatment would
      be serious. On the other hand, failure to correct hypoxaemia fearing from
      hypoventilation and carbon dioxide retention is not acceptable. For a safe oxygen
      treatment, doctor must know its indications, oxygen delivery systems, flow rates
      and monitoring. The aim of this review is to refresh our knowledge about when,
      how and how much to start oxygen treatment and how to monitor it.

PMID- 15143378
TI  - [A rare tracheal malignant tumor: mucoepidermoid carcinoma (a case report)].
AB  - An 18-year-old male preferred to our clinic with hemoptysis, cough, dyspnea and
      stridor. A wide-based polypoid tumor that was localized at the right wall of the
      distal trachea was observed over 3 cm from the carina by flexible bronchoscope.
      Computerized tomography showed an intraluminal soft tissue density mass in the
      trachea. Though right thoracotomy, a tracheal resection that contains three rings
      of the trachea with malignant lesion was performed. Pathologic examination
      reported a tracheal mucoepidermoid carcinoma. The patient is alive without
      recurrence three years after surgery.

PMID- 15143380
TI  - [Spontaneous remission in cancer].
AB  - Spontaneous remission of malignancy is a rare biological event. About 20 cases of
      regression of cancer are reported in the literature each year. This process is
      more rare in lung cancer than other solid tumors. Only six cases reported in the
      English literature this century. Spontaneous regression of lung cancer may be due
      to anti-tumor immune response or humoral factors. We reviewed related material in
      this paper.

PMID- 15143381
TI  - [Travel and pulmonary thromboembolism].
AB  - Pulmonary embolism is common cause of morbidity and mortality in immobile
      patients. Approximately 100 years ago,Virchow described a classical triad of
      local trauma to the vessel wall, hypercoagulability and stasis as cause of venous
      thromboembolism. Also prolonged travel is a risk factor for venous thromboembolic
      disease. The sitting position is caused by venous stasis and increased blood
      viscosity in the legs. The vessel lesions due to compression by the seat have
      been suggested as a cause of thrombosis. Addition in air travel relative hypoxia
      in the cabin of airplane reduces fibrinolytic activity and may lead to release of
      vein wall relaxin factors. Protective measures should include general advice to
      all passengers to avoid excess alcohol and caffeine, drink plenty of water and
      perform leg stretching exercises. Those with risk factors for deep vein
      thrombosis should carried out additional protective measures such as aspirin or
      low molecular weight heparin.

PMID- 15143382
TI  - [Development and treatment approaches of bronchopleural fistula after pulmonary
      resection].
AB  - Pulmonary resections comprise most of the operations performed in thoracic
      surgery departments. Diseases like pulmonary cancers, bronchiectasis, pulmonary
      abscess, tuberculosis and fungal infections are treated surgically by pulmonary
      resections. One of the important steps of the pulmonary resection is to suture
      the bronchi through which the air is supplied to the resected pulmonary tissue.
      Bronchopleural fistula developed in the bronchial stump is encompassed as one of
      the most important factors affecting mortality and morbidity regarding
      postoperative complications.

PMID- 15143383
TI  - [The evaluation of dyspnea and quality of life in COPD].
AB  - Dyspnea defined as an uncomfortable sensation of breathing is the main cause of
      disability in chronic obstructive pulmonary disease (COPD) patients. There is
      evidence that the underlying mechanisms of dyspnea are multifactorial. The aim of
      this study was to investigate these mechanisms causing dyspnea in COPD patients
      and the relationship between functional parameters, dyspnea scales and quality of
      life questionnaire. For this purpose 56 patients (11 female, 45 male) were
      recruited. Pulmonary function tests including airflow rates, lung volumes,
      maximal respiratory muscle forces, diffusing capacity, breathing pattern,
      arterial blood gas analyses as well as dyspnea scales MRC, baseline dyspnea index
      (BDI) and The Saint George Respiratory Questionnaire (SGRQ) were performed. The
      overall group showed moderate obstructive disease (FEV1%= 59.02 +/- 3.30) and
      mild hypoxemia with some air trapping (RV/TLC%= 52.00 +/- 2.00). MRC scale did
      not show any significant correlation with pulmonary function parameters. There
      was significant positive correlation between BDI and airflow rates, PImax, DLCO
      and air trapping. Breathing pattern parameters (Ti/Ttot, VT/Ti) also correlated
      with BDI. There was positive correlation between PaO2 and BDI (p< 0.001). SGRQ
      scores correlated significantly with FEV1, PImax, RV/TLC and P 0.1. There was
      also strong correlation between BDI and SGRQ scores. In conclusion, dyspnea is
      the result of multiple factors such as airflow limitation, decreased respiratory
      muscle strength, changes breathing pattern, hypoxemia, and air trapping which in
      turn affects quality of life in patients with COPD.

PMID- 15143384
TI  - [The levels of oxidant and antioxidant in patients with COPD].
AB  - It is determinate that oxidant-antioxidant imbalance is responsible for
      pathogenesis of chronic obstructive pulmonary disease (COPD) and smoking is
      playing a part in the pathogenesis. It was aimed to investigate the oxidant
      antioxidant imbalance in smokers and pathogenesis of COPD and their relations
      with lung functions. This study was done prospectively in Firat University
      Medical Faculty, Department of Chest Diseases. The levels of plasma
      malonyldialdehyde (MDA), erythrocyte reducted glutathione (GSH) and erythrocyte
      catalase were studied in 20 patients with COPD, in 20 smokers and in 20
      nonsmokers. All of the cases were male. Pulmonary function tests were done to all
      cases and the predicted values of FEV1, FVC, and FEV1/FVC were measured. The
      levels of plasma MDA: 1.44 +/- 0.23 nmol/mL, 1.51 +/- 0.27 nmol/mL and 1.29 +/-
      0.13 nmol/mL, the levels of erythrocyte GSH: 0.33 +/- 0.13 micromol/g.Hb, 0.34 +/
      0.17 micromol/g.Hb and 0.44 +/- 0.14 micromol/g.Hb and the levels of catalase
      were 22.82 +/- 17.47 k/g.Hb, 32.88 +/- 22.36 k/g.Hb and 55.73 +/- 26.56 k/g.Hb in
      patients with COPD, smokers and healthy nonsmokers respectively. There was no
      significance in each three parameters between smokers and patients with COPD. A
      significant difference was observed in each three parameters between nonsmokers
      and patients with COPD (MDA: p= 0.001, GSH: p= 0.028 and catalase: p< 0.001) and
      between smokers and nonsmokers (MDA: p= 0.035, GSH: p= 0.016 and catalase: p=
      0.005). In all three groups, no significant correlation was found between FEV1
      (predicted %), FEV1/FVC (predicted %) and the values of erythrocyte catalase, GSH
      and plasma MDA. In this study, there was an oxidant-antioxidant imbalance
      systemically in smokers and in patients with COPD. However, decreasing in the
      antioxidant capacity and/or increasing in the oxidant capacity either not
      correlate with spirometric measurements of airway obstruction in smokers or in
      patients with COPD were observed. We concluded that the use of cigarette
      increased oxidative stress by causing plasma lipid peroxidation and imbalance in
      erythrocyte antioxidant capacity.

PMID- 15143385
TI  - Elevated levels of circulating matrix metalloproteinase-9 in non-small cell lung
      cancer patients.
AB  - Elevated levels of matrix metalloproteinase have been implicated as playing
      important role in tumour progression in several types of cancers. Our aim was to
      determine whether these enzyme might be a useful tumour marker for lung cancer
      and also to evaluate the correlation of circulating levels of matrix
      metalloproteinase-9 (MMP-9) with tumour histology, staging, nodal status,
      metastasis and prognosis. Blood samples were collected from 35 nonsmall cell lung
      cancer patients who were diagnosed histologically, and 14 healthy controls. The
      MMP-9 levels were significantly higher in the cancer group (p< 0.001). However no
      significant correlation between several clinical features (such as histology of
      the tumour, staging, tumour status, or nodal status) and plasma MMP-9 levels have
      been observed. Though it does not show statistical significance, more patients
      with metastasis seemed to have higher MMP-9 levels. At the end of six month 11
      patients were out of follow-up. Among the remaining 24 patients eight patients
      had lower MMP-9 levels, seven were survivors at the end of six months. Sixteen
      patients had MMP-9 levels above the threshold. Only 10 have survived to six
      months. In conclusion MMP-9 can serve as a marker for metastasis and can be
      valuable in the follow-up of lung cancer patients.

PMID- 15143386
TI  - [The evaluation of excessive daytime sleepiness in taxi drivers].
AB  - Excessive daytime sleepiness (EDS) is a common but underrecognized and
      preventable cause of traffic accidents. It creates a problem of particular
      importance for professional drivers. We performed the Epworth Sleepiness Scale
      (ESS) and questionnaire related to their history of traffic accidents to 118
      professional taxi drivers to determine the EDS and its effects on driving
      performance in taxi drivers. There were 58 (49.2%) subjects with loud snoring, 8
      (5.9%) subjects with cardinal symptoms due to obstructive sleep apnea syndrome
      (OSAS) and 28 (23.7%) subjects with ESS > or =10 in the group of taxi drivers.
      Eighty (67.8%) drivers had been involved in a traffic accident. We found a
      significant relation between the number of traffic accident and EDS, witnessed
      apnea, cardinal symptom related to OSAS but not with snoring. The present data
      that sleepiness is a common symptom in taxi drivers and may be related to traffic
      accident.

PMID- 15143387
TI  - [Prevalence of smoking between the doctors, nurses and medical faculty students
      at some health facilities in Turkey].
AB  - Smoking is an important behaviour among health professionals who are role models
      for the public. For this reason 22 studies are selected which are smoking
      behaviours among doctors, nurses and students of medical school in Turkey.
      Smoking prevalence is found 32.6-66.2%, 40.3-68.6% and 15.1-36.6% among doctors,
      nurses and students of the medical faculties respectively. Smoking is fairly
      widespread among health professionals. Health professionals who are assumed to be
      role models for the public have to be considered primarily in cigarette control
      programs.

PMID- 15143388
TI  - [Diagnostic efficiency of pseudocholinesterase level in discrimination of
      transudates-exudates].
AB  - In this study, 80 cases with pleural effusion hospitalized at the departments of
      Chest Diseases and Internal Medicine in the Medical School of Selcuk University,
      and 30 healthy people as control group were studied. Regarding to the diagnosis,
      pleural fluids were classified into two groups as follows; transudates and
      exudates. Difference between the mean pleural pseudocholinesterase levels of
      transudates and exudates was statistically significant (p< 0.001). Similar
      significance was also obtained in the mean pleural fluid/serum
      pseudocholinesterase ratios of the groups (p< 0.001). In determination of
      exudative fluids both sensitivity and specificity of the pleural fluid
      pseudocholinesterase level was 100%. Sensitivity and specificity of the pleural
      fluid/serum pseudocholinesterase ratio were 90 and 87%, respectively. We have
      concluded that pleural pseudocholinesterase level and pleural fluid/serum
      pseudocholinesterase ratio can be used as a parameter with high diagnostic
      efficiency in discrimination of pleural effusions as exudates and transudates.

PMID- 15143389
TI  - [The value of fiberoptic bronchoscopy in diagnosis of smear negative pulmonary
      tuberculosis].
AB  - Although mycobacterial culture positivity is the gold standard for the diagnosis,
      the initial approach to the diagnosis of pulmonary tuberculosis (PTbc) is the
      detection of acid-fast bacilli (AFB) in respiratory specimens as recommended by
      the World Health Organization. But the physicians have to make a decision for the
      patients whose sputum smears are negative or who can not produce sputum. Waiting
      for culture results with radiological follow up or empirical antituberculous
      therapy are the standard options. In our study we aimed to assess the diagnostic
      yield of fiberoptic bronchoscopy in patients, suspected to have tuberculosis,
      whose sputum smears were negative or who could not produce sputum. Fifty six
      patients who suspected to have PTbc with sputum smear negative were enrolled in
      the study (fiberoptic bronchoscopy and selective bronchial washings were done to
      all patients. Bronchial washings were obtained from the affected parts). Mucosal
      biopsies were done in patients in where endobronchial abnormalities were noted.
      Transbronchial biopsies were done in selected patients from the radiological
      localizations. Ziehl-Nielsen staining and culture in Lowenstein-Jensen medium
      were the microbiological studies. Typical granulomas were expected to detect on
      histopathologic examination. Bronchoscopic lavage smears were positive for
      Mycobacterium tuberculosis in 13 (23%) patients. Twenty eight (50%) patients had
      positive culture. Histopathological results confirmed tuberculosis in eight of 20
      patients who had undergone mucosal biopsies, four of seven of transbronchial
      biopsies, two of three of needle aspiration biopsies. By bronchoscopic procedures
      early diagnosis was performed in 27 (48.21%) patients. We concluded that
      fiberoptic bronchoscopy has an important role in the diagnosis of patients
      suspected to have tuberculosis, whose sputum smears were negative or who could
      not produce sputum. It is useful and necessary in selected cases.

PMID- 15143390
TI  - [The cost of treatment in new case and multidrug resistant case in pulmonary
      tuberculosis].
AB  - The treatment of multidrug-resistant pulmonary tuberculosis (MDR-Tbc) is quite
      difficult, and the disease has high morbidity and mortality rates. This study was
      designed to compare the costs of treatment in new tuberculosis (new-Tbc) cases
      and MDR-Tbc cases. Data base of the study was composed of the data from therapy
      principles of new-Tbc cases and MDR-Tbc, and official directives and price lists
      of Turkish Pharmacology Society in 2001 fiscal year regulating treatment costs.
      For new-Tbc cases, the treatment cost included expanses for 20 days of
      hospitalisation, one month work loss and six months drug supply and laboratory
      costs; for MDR-Tbc cases, it was comprised by expenses for seven months
      hospitalisation in average, 12 months work loss, 24 months drug supply and
      laboratory costs, and probable surgical interventions and post-operative
      intensive care. The service of hospital stuff and medical equipment provided was
      disregarded. The cost analyses was calculated as charge price of American dollars
      ($) dated 14.09.2001. It was found that the cost of therapy for new-Tbc cases and
      MDR-Tbc cases were 1134.89 $ and 17529.15 $, respectively. In MDR-Tbc cases, the
      costs of hospitalisation, work loss, drug therapy and laboratory procedures were
      10.5, 12, 98.7 and 5.3 times higher respectively, when compared with those of new
      Tbc. The cost of thoracotomy for one patient including the cost for 10 days
      period of post-operative care in intensive care unit was 391.93 $. The treatment
      of MDR-Tbc has a high cost, and 16 new-Tbc cases can be treated with the same
      cost in our country. In conclusion, we think that successful treatment strategies
      for both new-Tbc cases and MDR-Tbc cases will lower the cost of tuberculosis
      treatment.

PMID- 15143391
TI  - [Pott's disease and different clinical presentations Pott's disease and different
      clinical presentations].
AB  - Skeletal tuberculosis remains a potentially crippling disease in the developing
      world; particularly as it usually affects children and young adults. The spine is
      involved approximately 50% of bone and joint tuberculosis cases. The features of
      four spinal tuberculosis cases were looked over this article. Their ages were
      between 18 and 76 years. All of them were male and immunocompetent. Pain was the
      major complaint. There was no life-threatening neurological sign. Among them, a
      case who was admitted to the hospital with painful torticollis had upper cervical
      lower thoracic spinal tuberculosis with psoas abscesses and peritoneal
      tuberculosis, but no pulmonary involvement. The other cases had thoracolumbal
      spinal tuberculosis with psoas abscesses and pulmonary tuberculosis of which
      miliary, chronic and new pulmonary tuberculosis. The whole diagnosis of spinal
      tuberculosis was made by radiographically-MRI and CT-. Specific antituberculous
      therapy with supportive care was begun and remarkable responses without surgical
      intervention were seen on them except miliary pulmonary tuberculosis case. The
      aim of this presentation was to emphasize the importance of early diagnosis so
      that adequate pharmacological treatment can be initiated to avoid serious
      complication.

PMID- 15143392
TI  - [Osteoarticular tuberculosis].
AB  - Tuberculosis (Tbc) remains as a major public health problem in the world.
      Extrapulmonary Tbc is gaining importance and it accounts for approximately 15% of
      all new cases. Osteoarticular Tbc is an infrequent form of the disease,
      accounting for 1-5% of all cases. Joints are uncommon site of infection;
      therefore, peripheral Tbc is considered rare. Tbc arthritis are usually
      monoarticular but oligoarticular involvement are also reported. We presented here
      four cases with osteoarticular Tbc and reviewed the literature.

PMID- 15143393
TI  - Endobronchial lipoma: a case report.
AB  - Endobronchial lipoma (EL) is a rare benign neoplasm that may cause irreversible
      pulmonary damage distally, and may be misdiagnosed clinically as a bronchial
      carcinoid or malignant tumor. They simulate malignant tumors, because of the age,
      sex and smoking history of the patients in whom they are found. Proper management
      is a "must" in order to avoid serious and unnecessary complications of the lung.
      We present a case of endobronchial lipoma, which is located in the right upper
      lobe bronchus, and diagnosed and treated by surgery.

PMID- 15143394
TI  - [Pleuropulmonary blastoma: a case report].
AB  - Pulmonary blastoma is a rare seen malignant tumor. It is generally reported in
      adults. The tumor including immature mesenchimal and/or epithelial structures is
      morphologically similar to fetal lung tissue. In this study, a male patient
      having been operated is presented because of the mass found in his chest X-ray.
      The lesion is histopathologically reported as a pleuropulmonary blastoma. The
      literature is reviewed because this case has a bad prognosis and is rarely seen.

PMID- 15143395
TI  - [Wegener granulomatosis: three cases].
AB  - Wegener granulomatosis (WG) is characterized by granulomatous vasculitis that
      involves multisystem, including upper and lower airways and kidney. WG may be a
      mortal disease if the diagnosis is delayed. The aim of this study is to present
      three patients admitted with different prediagnosis but after the investigations
      were diagnosed as WG and followed in our clinic. The cases were discussed with
      the literature knowledge. All three patients were diagnosed as WG with clinical,
      radiological and pathological findings. c-ANCA was positive in two patients, and
      negative one. Complete remission was established with treatment in one case. The
      treatment of other patients going on, however, the third patient was lost to
      follow up.

PMID- 15143396
TI  - [Quality of life in COPD].
AB  - Measurement of health related quality of life (HRQL) is quantification of the
      impact of disease on daily life and well-being in a formal and standardized
      manner. Chronic obstructive pulmonary disease (COPD) is essentially incurable,
      the therapy is directed towards minimization of symptoms, reduction of
      exacerbations and prevention of the decline in pulmonary functions also
      improvement in patients' HRQL. In COPD patients, impaired pulmonary function and
      limited exercise capacity may result in quality of life. As the relationship
      between respiratory impairment and HRQL is generally weak; it's important to
      evaluate HRQL in patients with COPD. In this review, general and disease specific
      questionnaires and assessment of COPD patients is evaluated in the light of
      recent literatures.

PMID- 15143397
TI  - [Gene therapy in malignant mesothelioma].
AB  - Malignant mesothelioma which arises from pleural mesothelial cells is a rare and
      deadly disease. Environmental factors, especially the exposure of asbestos, are
      accepted as etiological factors. There is not any accepted treatment of malignant
      mesothelioma. Nowadays four main forms of therapy and the combination of these
      forms are put in the practise for the treatment of malignant mesothelioma. These
      are surgical therapy, chemotherapy protocols, radiotherapy protocols and recently
      immunologic therapy which is based on direct antiproliferative effect of
      interferon. Gene therapy has been studying experimentally for recent years. The
      main principles of the gene therapy is sensitizing to antiviral drugs by
      infecting and changing the gene structure of the malign cells. The most used gene
      is herpes simplex virus (HSV) tk gene. In malignant mesothelioma, there is no
      standard treatment protocol and the main cause of death is local spread of tumor
      and the pathological effects of its mass rather than metastasis and the diagnosis
      and treatment results are evaluated from the same localization (pleural space).
      According of these factors, gene therapy could be an appropriate treatment for
      malignant mesothelioma.

PMID- 15143398
TI  - [Pulmonary function and nutrition].
AB  - Respiratory system disease itself can cause malnutrition, while nutritional
      status can be the cause of or enhance respiratory failure. Malnutrition which
      exists 27-71 percent in chronic obstructive pulmonary disease, is a factor that
      determines functional capacity and mortality.

PMID- 15143399
TI  - Effects of atmospheric sulphur dioxide and particulate matter concentrations on
      emergency room admissions due to asthma in Ankara.
AB  - Recent studies have associated short-term exposure to respirable particulate
      matter (PM(10)) and sulphur dioxide (SO(2)) with peak flow decrements, increased
      symptoms of respiratory irritation, increased use of asthma medications, and
      increased admission and hospitalization for asthma. To further delineate the
      association between SO(2), PM(10) exposure and asthmatic response, we compiled
      daily records of asthma emergency room visits from our hospital and data of
      meteorological conditions, SO(2) and PM(10) concentrations in Ankara area. Weekly
      averages of daily counts of emergency room visits for asthma were significantly
      associated with average weekly SO(2) and PM(10) exposure on previous week (r=
      0.328, p= 0.017 and r= 0.355, p= 0.009 respectively). Admission to emergency room
      for asthma count was also negatively correlated with ambient temperature (r= 
      0.496, p= 0.0001) and strong wind existence (X(2)= 3.930, p= 0.047) on previous
      days. It was also positively correlated with ambient relative humidity (r= 0.531,
      p= 0.0001). We observed that numbers of emergency visits due to asthma were
      higher in winter months, April and September. In winter and early spring period
      there was concordance between asthma emergency admissions with air pollutants
      levels. During this period ambient temperatures were low as well. There were two
      discordance points in monthly variation of air pollution and asthma visits. We
      thought that first asthma visits peak was related to allergic pollens during
      April and second peak was due to opening of schools and increasing of respiratory
      infections for this reason during September. The general pattern of our results
      confirms that even low levels of air pollution encountered in Ankara are linked
      to short-term increases in the number of people visiting emergency department for
      asthma.

PMID- 15143400
TI  - Nutritional status of COPD patients with acute exacerbation.
AB  - The prevalence and features of nutritional status in patients with chronic
      obstructive pulmonary disease (COPD) have been studied extensively in stable
      conditions, but are poorly defined in the presence of an acute exacerbation. The
      aim of this study is to evaluate the nutritional status of COPD patients with
      acute exacerbation and possible relationship between nutritional parameters and
      pulmonary functions. The study group consisted of 53 COPD patients acutely
      admitted to the hospital for standardized medical treatment. The nutritional
      status of patients was assessed by anthropometric measurements, biochemical
      analysis, and immunologic testing. The patients were divided into two groups as
      having severe (FEV1 < 50%) and mild to moderate (FEV1 ? 50%) COPD and weight loss
      greater than 5% for the comparison of the study parameters. Ideal body weight
      (IBW%) was found as 104.42 +/- 4.30 in severe COPD, where as it was 115.31 +/-
      7.28 in mild to moderate COPD group (p= 0.07). There was no relationship
      demonstrated between IBW% and FEV1. IBW% was correlated with DLCO for the total
      study population (r= 0.353, p= 0.035). Weight loss greater than 5% of body weight
      (BW) was observed in 54% of patients. Comparison of the patient's actual weight
      to their usual weight revealed statistically significant weight loss (p< 0.01).
      Mean values of serum albumin, transferrin were found in normal range. Delayed
      type hypersensitivity skin test revealed normal immune status. When the study
      parameters were compared, no any statistically significant differences in
      parameters related to nutritional status were detected, between severe and mild
      to moderate COPD groups. As a statistically significant weight loss was found
      between the actual and usual weights of the patients, monitoring of nutritional
      parameters and eventual dietetic treatment should also be included in the goals
      of the medical treatment of patients with COPD in acute exacerbation.

PMID- 15143401
TI  - [The effect of hyperinflation on respiratory muscles and breathing pattern in
      COPD].
AB  - Lung hyperinflation is a consequence of airway obstruction, increased airway
      resistance and compliance in patients with chronic obstructive pulmonary disease
      (COPD) which may result in respiratory muscle fatigue and deterioration of gas
      transfer. The aim of this study was to investigate the influence of
      hyperinflation on respiratory muscles, gas transfer and breathing pattern and
      compare the differences between mild and severe COPD. Twenty-eight COPD patients
      with radiological and tomographic evidence of emphysema were included in the
      study and they were divided into two groups according to the severity of COPD.
      Group I= FEV(1) < or = 49% (n= 16). Group II= FEV(1) > or = 50% (n= 12). Airflow
      rates were decreased and airway resistance was increased significantly in Group
      I. Maximal inspiratory pressure (MIP) was significantly reduced in Group I. FRC,
      RV and RV/TLC ratio were increased above 120% in both groups with more
      significant increase in Group I. Group I showed moderate hypoxemia (PaO(2) =
      54.02 mmHg) with hypercapnia (PaCO(2)= 46.65 mmHg) whereas Group II patients were
      mildly hypoxemic (PaO(2)= 63.78 mmHg) with normocapnia. Parameters of breathing
      pattern were similar in both groups. Diaphragm height index (DHI) didn't showed
      significant difference between groups. But there were significant correlations
      between DHI and RV, FRC. MIP showed significant positive correlation with airflow
      rates and DLCO, negative correlation with lung volumes, positive correlation with
      PaO(2) and negative correlation with PaCO(2). FRC also negatively correlated with
      Ti and Ti/Ttot. In conclusion, hyperinflation present even in the mild forms of
      COPD causes inspiratory muscle weakness which in return results in impairment in
      gas transfer.

PMID- 15143402
TI  - [Results of surgical treatment for lung cancer in advanced age].
AB  - In this study, 24 patients aged 70 and over who were operated for primary
      bronchogenic carcinoma were reviewed retrospectively and their results were
      compared with those of 90 patients under 70, whom operated for the same intent.
      The mean age and age range of the group were 74.6 +/- 3.3 and 70-86,
      respectively, and it consisted of 21 male and three female patients. The
      histology of the tumor revealed epidermoid carcinoma in 16 (67%) patients,
      adenocarcinoma in 6 (25%), and large cell carcinoma in 2 (8%). Twelve of the
      elderly patients had associated diseases (six had coronary artery disease and/or
      hypertension, four had chronic obstructive pulmonary disease and two had
      diabetes) that increased the operative risk. The resection type used most
      frequently was lobectomy (67%), followed by limited resection (25%). In
      postoperative staging, nine patients were found to have stage I disease, nine
      stage II disease, four stage IIIA disease and two stage IIIB disease. Three (13%)
      patients developed major complications, and postoperative mortality rate within
      30 days was 4% with one patient. In the patients aged under 70, the last two
      variables were noted in 10 (%11) cases and in 1 (%1) case respectively, and the
      difference between the two groups was statistically insignificant. As a result,
      with appropriate patient selection and vigorous postoperative care, morbidity and
      mortality of the pulmonary resections in elderly is not higher than in young
      patients, and a curative resection should be preferred.

PMID- 15143404
TI  - [Diagnostic efficiency of serum lipid-bound sialic acid level in malignant
      pleural effusions].
AB  - In this study, pleural fluid and serum lipid-bound sialic acid (LBSA) levels of
      68 cases with pleural effusion hospitalised at the department of Chest Diseases
      in the Medical School of Selcuk University, and serum LBSA levels of 30 healthy
      individuals as control group were studied. Pleural effusions of 32 cases were due
      to malignancy of which considerably lung cancer. In the other 36 cases the causes
      were nonmalignant in origin. Levels of mean serum LBSA in malignant and benign
      groups were significantly higher than control group (p< 0.001). However,
      difference of the mean serum LBSA levels of malignant and benign groups was not
      statistically significant. We found the mean pleural fluid LBSA level of 23.34
      mg/dL in malignant group and it was significantly higher than benign group (17.97
      mg/dL) (p< 0.05). It was observed that there was no significant statistical
      difference between the pleural fluid to serum LBSA ratios of malignant and benign
      groups. In differential diagnosis of malignant pleural effusions, sensitivity and
      specificity of pleural fluid LBSA were 91%, and 51%, respectively. In conclusion,
      for the differentiation of malignant pleural effusions LBSA is not believed to be
      a reliable tumor marker since it may also increase in various chronic and
      inflammatory diseases. Despite of that, in cases with a suspicion of malignancy,
      the increased level of pleural fluid LBSA may be useful as a supportive
      parameter.

PMID- 15143403
TI  - [Diagnostic value of postbronchoscopic sputum, bronchoscopic lavage, and
      transbronchial biopsy in peripheral lung cancer].
AB  - The aim of this prospective study was to review the value of bronchoscopic
      lavage, transbronchial biopsy and postbronchoscopic sputum cytology in peripheral
      lung cancer. Two groups of patients were involved in the study who were treated
      in our clinic between the years 1999 and 2001: Group I (22 patients; average age
      64 +/- 9 years; 18 males and four females) whose lesions were peripherally
      localised on chest radiographs and Group II (28 patients; average age 61 +/- 8;
      26 males and two females) whose lesions were centrally localised and were visible
      only by diagnostic bronchoscopic procedures. The following procedures and
      analysis were done in all patients: Cytologic analysis of prebroncoscopic sputum,
      bronchoscopic lavage, bronchial biopsy, and patients were asked to give sputum in
      30 minutes after bronchoscopy. The final diagnosis of all patients was primary
      lung cancer. In the first group none of the patients had visible endobronchial
      lesion on fiberoptic bronchoscopy. Sputum cytology of the patients were negative
      before bronchoscopy. Bronchoscopic lavage cytology was positive in five of 22
      patients (22.7%). Transbronchial biopsy provided better diagnostic yield (50%)
      than postbronchoscopic sputum (31.8%). In the second group of patients, cytologic
      analysis was positive 25%, 96.4% and 42.9% in bronchoscopic lavage, bronchial
      biopsy and postbronchoscopic sputum respectively. Our findings suggest that
      postbronchoscopic sputum cytology may be an important diagnostic procedure in
      endoscopically nonvisible pulmonary cancer. Since its application is easy and
      noninvasive, cytologic analysis of postbronchoscopic sputum may be preferable to
      bronchoscopic biopsy although a favorable diagnostic yield is not expected.

PMID- 15143405
TI  - [Respiratory findings and pulmonary function tests among the welders working for
      the sugar plant factory].
AB  - Industrialization and developments in technology run together with health
      problems in workers. The aim of this study was to examine the effects of the
      exposure of welding fume on respiratory system. This study was carried out in 32
      welders in the "Sugar Factory" in Ankara. As controls, 39 workers who were not
      exposed to weld fume were included in the study. A questionnaire about
      respiratory symptoms and exposure history, and pulmonary function tests were
      obtained and compared between the groups. The incidence of coughing, sputum and
      dyspnea was found to be statistically greater in the group of welders (65.6%,
      84.4%, 68.8%) compared with the control group (33.3%, 41%, 30.8%) (p< 0.05, p<
      0.001, p< 0.01). Coughing alone was present in 72.7% of smoking welders whilst
      sputum production was present in 90.9%. These rates were found to be lower in ex
      smoker welders or the welders who had never smoked. Chronic bronchitis was
      observed in 21.9% of the welders whereas no cases with chronic bronchitis were
      found in control group. The difference was statistically significant (p< 0.01).
      The results of pulmonary function tests were not statistically different in
      welders and control group. These results indicate that the exposure of weld fumes
      itself may cause respiratory symptoms particularly related with chronic
      bronchitis therefore a great caution must be taken when dealing with welding.

PMID- 15143406
TI  - [Serum adenosine deaminase activity in pulmonary tuberculosis].
AB  - Adenosine deaminase (ADA) activity has been helpful for the diagnosis of
      tuberculous pleurisy. However, there are few studies about the role of ADA in the
      diagnosis and follow-up of pulmonary tuberculosis. In our study, serum ADA
      activity was determined in order to investigate the role of the enzyme in the
      diagnosis of pulmonary tuberculosis and monitoring the efficiency of therapy. The
      ADA activity was (mean +/- SD) 21.77 +/- 8.51 U/L in pulmonary tuberculosis
      patients (n= 44), 6.24 +/- 3.25 U/L in old tuberculosis patients (n= 24), 8.58 +/
      4.38 U/L in healthy control subjects (n= 20), whereas the mean for the patients
      with bronchial cancer (n= 20) was 18.51 +/- 7.85 U/L. There was no statistical
      difference between the results of pulmonary tuberculosis patients and the
      patients with bronchial cancer. On the contrary, the result of these two group
      were significantly different from both old tuberculosis patients and healthy
      control subjects (p< 0.001 for both). In 10 pulmonary tuberculosis patients, ADA
      activities were determined both before and after treatment and a significant
      decrease was observed in ADA activities after treatment (p< 0.001). In
      conclusion, serum ADA activity is increased in pulmonary tuberculosis patients,
      therefore it may be a helpful parameter for monitoring therapy.

PMID- 15143407
TI  - [The evaluation of close contact case of pulmonary tuberculosis patients enrolled
      to Eskisehir Deliklitas Tuberculosis Control Dispensary].
AB  - Persons infected with Mycobacterium tuberculosis are at greatest risk for
      developing active tuberculosis especially in children, adolescents, young adults
      and persons who have selected risk factors. Persons who were contact with
      tuberculosis patients and who have positive tuberculin skin test reactions and
      had high risk for developing active tuberculosis should be use preventive
      chemotherapy. In this study, we aimed to evaluate retrospectively 1663 close
      contacts of 486 active tuberculosis patients who registered in Eskisehir
      Deliklitas Tuberculosis Control Dispensary. The mean age was 25.4 +/- 18.1 years,
      961 (57.7%) cases were female and 702 (42.3%) cases were male. Diagnosis was
      performed 1114 (67%) of close contacts people's patients with microbiological
      study. The scatrix of BCG has been recorded 901 (54.2%) cases, tuberculin skin
      test results has been recorded 952 (57.2%) cases. Tuberculin skin test of 612
      (64.5%) cases were above 15 mm. 37.8% of cases were used preventive chemotherapy
      and 2.6% of cases had active tuberculosis disease. The age group was 7-14 years
      and persons who had close contacts of bacile positive patients, 80.5% of them had
      used preventive chemotherapy. Persons who's tuberculin skin test positive and
      younger than 6 years, 98.5% of them had preventive chemotherapy. Only 372 (59.2%)
      of patients completed preventive chemotherapy. At the results; we established
      that the preventive chemotherapy programme which recommended to our country is
      using regularly, but most of the close contact patients didn't completed their
      therapy.

PMID- 15143408
TI  - [Evaluation of Nazilli Tuberculosis Dispensary activities executed between June
      1996-May 2000: Pre-DOT situation].
AB  - OBJECTIVE: To evaluate Nazilli Tuberculosis Dispensary activities executed
      between 1st June, 1996- 31st May, 2000 and to compare differences among 12-month
      periods. DESIGN: Retrospective analyses of data. SETTINGS: People living in the
      villages under responsibility of Nazilli Tuberculosis Dispensary. POPULATION:
      People examined in out-patient clinic as symptomatic cases, for health report or
      during contact examination, number of mycobacteriological and radiological
      examinations, and tuberculosis cases detected in each year. MAIN RESULTS: Average
      number of newly diagnosed tuberculosis patient in every 12-month-period was 105.
      The average rate for new tuberculosis cases finding was 52.5%. Pulmonary
      tuberculosis was in 74.8% of all tuberculosis cases. The range of smear positive
      pulmonary tuberculosis cases in all tuberculosis cases differed from 49% to 71%
      and a decrease in the rate of cases with no sputum smear from 18% to 3% were
      observed. The average of bacteriological conversion rate at the end of second
      therapy month was 70.5%. The average of cure rate in new smear positive patients
      was 82%. According to drug susceptibility test results, 13 of new smear positive
      cases and 5 of old cases were multi-drug resistant tuberculosis. CONCLUSION:
      Although the treatment success of either new smear positive or old smear positive
      tuberculosis cases were high, it is necessary to plan strategies for increasing
      the new case finding rate to 70%, the rate suggested by World Health
      Organization. The data obtained by this study showed that hopeful results may be
      achieved by stable staff and team-work in tuberculosis dispensary.

PMID- 15143409
TI  - [Symptomatic intracranial tuberculoma revealed when the patient receiving therapy
      for miliary tuberculosis: a case report].
AB  - We describe a 20 year old man with miliary tuberculosis of the lung, who was
      noted to have multiple intracranial tuberculomas on magnetic resonance imaging
      but not noncontrast head computed tomographic scan receiving antituberculous
      chemotherapy.

PMID- 15143410
TI  - [A patient with meningeal carcinomatosis and small cell lung cancer].
AB  - Cranial metastasis because of lung cancer shows the poor prognosis. Cranial
      metastasis is common: In order lung, breast, skin, kidney, gastrointestinal
      system cancer is the 80% of the cause of metastasis. Cranial metastases are
      common in lung cancer especially in small cell lung cancer. Cranial metastasis
      can be seen in different location but leptomeningeal infiltration is rare and
      interesting. Because of this we will describe a case which has been death seven
      months after diagnose because leptomeningeal infiltration of small cell lung
      cancer.

PMID- 15143411
TI  - [A case of aggressive fibromatosis of posterior mediastinum].
AB  - Aggressive fibromatosis is a rarely seen soft tissue tumor. They originate
      principally from deep seated fascial or musculoaponeurotic structures. Although
      they are considered histologically benign, they behave locally aggressive.
      Posterior mediastinal localisation is very rare. The patient who was investigated
      because of a lesion located in posterior mediastinum and a thoracal magnetic
      resonance imaging revealed a mass with a dimension of 20 x 6 x 5 cm, started at
      the level of thoracal fourth vertebra reaching the L1 vertebra, was diagnosed as
      aggressive fibromatosis by a biopsy obtained after a right posterior thoracotomy
      performed by thoracic surgery. A minimal regression was established nine months
      after radiotherapy by thoracal MRI. This case of aggressive fibromatosis, which
      was asymptomatic and whose posterior mediastinal mass did not increased its
      dimensions during six years of follow-up, was presented.

PMID- 15143412
TI  - [Treatment of malignant pleural mesothelioma].

PMID- 15143414
TI  - [Nebuliser therapy].
AB  - We use the nebuliser therapy to achieve rapid improvement in patients with acute
      airway limitation. Besides, this drug is effective in asthmatic children, in
      elderly patients and in patients with end-stage disease who need palliative care.
      Nowadays nebuliser therapy is used not only for bronchodilatation but also for
      antibiotic and expectoration treatment. Although nebuliser therapy provides a
      rapid and effective treatment in airway limitation, the patients who receive home
      nebuliser therapy may suffer from severe and incurable infections if the hygienic
      conditions are not achieved. Therefore, the indications of nebuliser therapy
      should be precisely determined and special care should be given in the choice of
      the patients who will receive nebuliser therapy.

PMID- 15143413
TI  - [Using of fibrinolytics in the treatment of complicated parapneumonic effusion
      and empyema in children].
AB  - Bacterial pneumonia is associated with a high incidence of pleural effusions in
      children. These parapneumonic effusions usually resolve spontaneously if patients
      are treated with appropriate antibiotics. However, a small percentage of
      parapneumonic effusions will become complicated, either loculated non-purulent
      fluid or an empyema. The traditional therapeutic approaches for complicated
      parapneumonic effusions includes catheter drainage and systemic antibiotics. Tube
      drainage often fails if the fluid is loculated by fibrinous adhesions and
      surgical operation require. Intrapleural administration of fibrinolytics is an
      effective treatment for complicated parapneumonic effusions and pleural empyemas,
      improving the drainage without causing systemic fibrinolysis or local hemorrhage.
      The global success rate were between 44% and 100%, in most cases more than 80%.
      Both streptokinase and urokinase have been used for this purpose but there are
      few reports of their use in the children. Intrapleural streptokinase and
      urokinase are equally efficacious in treating complicated parapneumonic effusions
      and empyemas. Intrapleural instillation of fibrinolytics is an effective and safe
      mode of treatment for complicated parapneumonic effusions and pleural empyemas,
      and may reduce the need for more invasive surgical procedures.

PMID- 15143415
TI  - [Overlap syndrome].
AB  - The term overlap syndrome (OVS) in sleep disorders is used to describe the
      association of obstructive sleep apnea syndrome (OSAS) with one of the following
      disorders: chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis
      and interstitial lung diseases. Because OSAS and COPD are seen together
      frequently, the term of OVS is often used for OSAS associated with COPD. In both
      OSAS and COPD, some abnormalities on the level of oxygen saturation occur during
      sleep. These abnormalities are much more serious in the OVS. Oxygen desaturation
      destroys the architecture of sleep and leads to the complications due to
      hypoxemia, which are normally seen in the late stage of each disease, occur in
      early stage. In this review, interaction of sleep and some of the lung diseases
      was discussed.

PMID- 15143416
TI  - [Central sleep apnea syndrome].
AB  - Central sleep apnea syndrome (CSAS) is a disorder characterized by repeated
      apneic events during sleep with no associated ventilatory effort. CSAS is
      classified as either hypercapnic or non-hypercapnic. In the hypercapnic form of
      CSAS, increases in PaCO(2) generally result from reductions in ventilation or
      outright apneas due to an underlying depression of respiratory drive. Hypercapnic
      CSAS is common in central hypoventilation syndromes which may be primary
      (idiopathic) or secondary to other disorders that cause damage to the respiratory
      center. Non-hypercapnic CSAS is not associated with either a primary reduction in
      respiratory drive or respiratory muscle weakness. Non-hypercapnic CSAS can be a
      primary disorder or can occur secondary to high altitude, other medical illnesses
      such as congestive heart failure and central nervous system disease.

PMID- 15143417
TI  - The cellular inflammation of bronchial biopsies in chronic obstructive pulmonary
      diseases.
AB  - This study was designed to describe the cellular inflammation, thickness of
      basement membrane (BMT) and epithelial desquamation (ED) in bronchial biopsies
      from patients with chronic obstructive pulmonary disease (COPD) compared with
      asthma and healthy individuals. Thirteen subjects with COPD, 12 asthmatic
      subjects, and 10 healthy individuals enrolled in the study. Bronchial biopsies
      obtained by fiberoptic bronchoscopy were stained with hematoxylin and eosin to
      perform cell counts and descriptive analysis. Neutrophils were found in higher
      numbers in epithelium and lamina propria in subjects with COPD compared with
      asthma and control groups (p< 0.001, p< 0.05) whereas eosinophils were observed
      higher in epithelium and lamina propria in asthmatic subjects (p< 0.001, p<
      0.001). There were no significant differences in numbers of neutrophils and
      eosinophils in submucosa in the three groups (p> 0.05). There were no significant
      correlations between the inflammatory cell counts and FEV1 or smoking history in
      either group (p> 0.05). In subjects with COPD only 6 (46.2%) of the subjects
      showed BMT whilst 2 (15.4%) of the subjects showed ED. In asthma group, 11
      (91.7%) of the subjects presented increased BMT and ED. In healthy individuals 1
      (10%) of the subjects had increased BMT and no one had ED. As a result, we may
      conclude that the predominant cells of bronchial mucosa in COPD are the
      neutrophils whereas they are eosinophils in asthma. Thickening of basement
      membrane and epithelial desquamation are the major features of asthmatics.
      However in COPD, these features would be focally present and variable.

PMID- 15143418
TI  - [Effects of salbutamol and ipratropium bromide on arterial blood gases in
      patients with stable COPD].
AB  - The aim of this study was to evaluate the acute effects of inhaled salbutamol and
      ipratropium bromide on arterial blood gases in patients with chronic obstructive
      pulmonary disease (COPD). We measured arterial blood gases and spirometry after
      inhalation of salbutamol (200 micro g) or ipratropium bromide (36 micro g) in 25
      patients with COPD. After at least 2 days of washout period, the same patients
      inhaled the other drug, and the procedure of study was repeated. Blood specimens
      were taken just before the inhalation and at 5, 10, 20, 30, 60, 90,120 minutes
      after inhalation, and spirometry was done before and 60 minutes after inhalation.
      Both drugs caused a small decrease in PaO(2) levels, however the decrease in
      PaO(2) after inhalation of salbutamol was significantly higher than that after
      ipratropium (p< 0.05). Both drugs caused a little, but not statistically
      significant decrease in D(A-a)DO(2) and PaCO(2) (p> 0.05). There were a little
      increase in FEV1 and FVC at 60 minutes after inhalation of both drugs, especially
      with salbutamol, compared to ipratropium bromide; but both increases were
      statistically insignificant (p> 0.05). The results revealed that, salbutamol
      caused a significant, but small and transient decrease in PaO2 and a little, but
      insignificant increase in D(A-a)DO(2) when used in recommended doses. Although
      salbutamol and ipratropium bromide which are used in treatment of COPD, can cause
      small decreases in PaO(2) after inhalation, the declines are trancient and
      clinically insignificant.

PMID- 15143419
TI  - [Investigation of pollens, fungal spors and other materials in houst dust of
      Isparta].
AB  - In this study allergic materials in house dusts collected from preselected
      stations in Isparta between April 1996 and March 1997 are investigated. Ten
      stations were preselected for the study. Dusts vacuumed in vacuum cleaners are
      collected regularly from selected houses every month. Preparations were prepared
      with Wodehouse method. These preparations were investigated microscopically and
      diagnosis and counts of pollens, fungal spors, plant tissues, and starch
      particles per 4 cm(2) in respect to months are performed. Obtained results are
      transformed to allergic material per square centimeters and are shown with tables
      and graphics. As a result, pollens belonging to 44 taxons are detected in Isparta
      house dusts. Annual total pollen per cm(2) is found as 277.5. Among these pollens
      most frequently seen are Pinaceae, Poaceae, Asteraceae and Cupressaceae
      respectively. While starch is first in order (2224/cm(2)), plant tissues are seen
      133/cm(2) and fungal spors are seen 17.1/cm(2). Allergic pollens for Isparta are
      Poaceae, Asteraceae and Cupressaceae and as the other, fungal spors. We believe
      that our results will be helpful for the physicians in diagnosis and treatment of
      patients with allergic disorders.

PMID- 15143420
TI  - [The effects of hypertonic NaCl (7.5%) in dogs with induced acute pulmonary
      artery obstruction].
AB  - The study was performed on 11 female and 9 male dogs to investigate the effect of
      hypertonic NaCl in severe hypotension and shock caused by acute pulmonary artery
      obstruction. The investigation was performed in Dicle University Healt Research
      Center (DUHRC). The youngest subject was six months old and the oldest was two
      years old. Their mean body weight was found as 19 kg. All the subjects were
      operated under general anesthesia. Invasive measurements of arterial pressure
      were performed through the right femoral artery by monitorization. All subjects
      were performed left thoracotomy, entrance to thorax was through 5th intercostal
      space, and first left then right pulmonary artery were circumferenced loosely
      with tape. After this, mean pulmonary artery pressures are recorded with the help
      of monitor by inserting canulla into the pulmonary artery. Pulmonary artery
      pressures at 3rd, 5th, 10th, 13th, 15th, 18th and 21st minutes after ligation of
      right main pulmonary artery and left lower lobe pulmonary artery, and mean artery
      pressures are recorded. Sodium nitroprusside is given to half of the subjects and
      nitroglycerine is given to the other half in order to lower pulmonary
      hypertension. Pulmonary arterial pressure measurements following administration
      of these drugs are recorded. 7.5% of NaCl infusion to subjects is performed in
      case of hypotension and shock. Isotonic NaCl solution is used in the control
      group. Mean arterial pressures in group receiving sodium nitroprusside + 7.5%
      NaCl solution are found significantly higher statistically when compared to group
      receiving sodium nitroprusside + 0.9% NaCl isotonic solution. Difference in mean
      arterial pressures were not found statistically significant in the group
      receiving nitroglycerin + 7.5% NaCl when compared to group receiving
      nitroglycerin + 0.9% NaCl solution.

PMID- 15143421
TI  - [In which stage we diagnose and how we treat lung cancer?].
AB  - To determine the stage of the disease, performance status of the patients on
      admission and treatment modalities, records of 226 patients with lung cancer
      diagnosed between January 1992 and December 1999 were evaluated retrospectively.
      The mean age of the patients were 61.3 +/- 10.3 years (mean +/- standard
      deviation) and 217 (96%) were men and 9 (4%) were women. Of the 192 cases with
      non-small cell lung cancer 22.9% were stage 4, 40.6% were stage 3b, 22.4% were
      stage 3a, 4.2% were stage 2, 9.9% were stage 1. Of the 34 (15.1%) patients with
      small cell lung cancer, 26.5% were extensive and 73.5% were in limited stages.
      The performance status according to European Cooperative Oncology Group (ECOG)
      was between 0-2 in 88.4% and 3-4 in 11.6% of the cases. A positive correlation
      between the performance status and the stage of the disease was observed (p=
      0.0331). It was detected that the performance status of the patients who
      underwent surgery was better than the patients who treated with radiotherapy (p=
      0.0008). Radiotherapy (RT), chemotherapy (CT), surgery, combined therapy (RT +
      CT), adjuvant RT and palliative therapy were performed in 27%, 20.4%, 11.5%,
      1.3%, 1.8% and 14.6% of the cases respectively. No information about treatment
      protocol was able to obtained in 23.4% of the patients, probably due to
      referrals, early deaths etc. In conclusion, more than half of our cases with lung
      cancer were diagnosed in advanced stages as a possible result of late admission
      to physician and surgery were performed in only a small part of the cases. It was
      detected that performance status of the patients operated was better than the
      patients treated with radiotherapy. On the other hand, combination therapy was
      applied in few cases.

PMID- 15143422
TI  - [Diagnostic value of Tc-99m MIBI scintigraphy in the differential diagnosis of
      malign and benign of intrathoracic pathologies].
AB  - This study was conducted to assess the feasibility of using Tc-99m labelled 2
      methoxy isobutyl isonitrile (MIBI) scintigraphy, to evaluate benign and malignant
      intratoracic lesions and to assess the value in the differential diagnosis. The
      eligible population of the study included randomly selected 37 patients examined
      in Kocaeli University Pulmonary Clinic (19 men, 18 women) who had a abnormality
      in the PA chest X-ray and hadn't received any therapy. After intravenous
      injection of 15-25 mCi Tc-99m MIBI, early (10 minutes) and delayed (2.5 hours)
      static spot images of posterior and anterior thorax and SPECT images were
      obtained. Assessment of MIBI uptake was done visually. Of the 18 patients with
      primary bronchial carcinoma, increased abnormal uptake of MIBI corresponding to
      the location of lesion was reported in 14 patients with planar imaging and in 15
      patients with SPECT and was considered positive. Three patients had no abnormal
      activity. Of the 19 patients with benign lesions, four had abnormally increased
      uptake of MIBI. In the detection of malignant lesions Tc-99m MIBI has 83.3%,
      78.9%, 78.9%, and 83.3%, specificity, sensitivity, positive predictive value and
      negative predictive value respectively. Tc-99m MIBI tumor scintigraphy might be a
      valuable non-invasive method in the differential diagnosis of malignant and
      benign lung lesions. However further study with larger series for the relatively
      low sensitivity and specificity.

PMID- 15143423
TI  - [The evaluation of pulmonary tuberculosis patients enrolled to Eskisehir
      Deliklitas Tuberculosis Control Dispensary].
AB  - Tuberculosis is an important public health problem in our country. Tuberculosis
      Control Dispensary has been important role in tuberculosis control programme. In
      this study we retrospectively evaluate 891 pulmonary tuberculosis patients who
      registered in Eskisehir Deliklitas Tuberculosis Control Dispensary between
      January 1990 and June 2000. The mean age was 38.9 +/- 15.7 years, 159 (18.3%)
      patients were female, 710 (81.7%) patients were male. The most common symptom was
      cough (88.7%). 81 percent of patients have been found by examination of
      symptomatic people while 6.4 percent of them by examination of close contacts.
      26.5 percent of patients had close contacts with tuberculosis patients. The
      scares of BCG vaccine has been recorded 63.6% of the patients and 80.3% percent
      of them had at least one scare, tuberculin skin test result has been recorded in
      49.6% percent of patients. Cavitary pulmonary tuberculosis was a diagnosed of
      27.7%. The sputum examination and culture for acid resistant basil has been
      performed 89.1% of the patients, 389 (50.2%) of patients had acid fast bacillus
      in sputum and 548 (70.8%) of patients had culture positivity. 80.3 percent of the
      patients has completed regularly their treatments (mean duration 10.4 +/- 2.6
      months). The mortality rate was 5.8%.

PMID- 15143424
TI  - [Determination of self-esteem levels of patients with tuberculosis].
AB  - Tuberculosis patients and determining the perception of their illnesses are
      important in increasing treatment adaptation. Decrease in self-esteem because of
      illness cause losing self confidence, deteriorating social relations and giving
      up struggle against illness. The aim of this study was to determine self-esteem
      levels of patients with tuberculosis. Descriptive and cross section study. Study
      was done on patients (n= 120) who were treated for pulmonary tuberculosis in
      "Izmir Chest Diseases and Surgical, Education, Practice and Research Hospital"
      between January 2001 and February 2001. Average self-esteem points of the
      patients were found to be 57.50 +/- 14.09 (minimum 24, maximum 84). It was
      observed that being unemployed and housewife, not having a job, effects on
      economic status of the patient, not having a hope to recover, change in family
      and social relations and not having social support decreased average self-esteem
      points of the patients.

PMID- 15143425
TI  - [Invasive pulmonary aspergillosis in solid organ transplant recipients].
AB  - To discuss diagnosis, risk factors, clinical and radiologic manifestations of
      invasive pulmonary aspergillosis (IPA) that is accepted as an important mortality
      factor in organ transplant recipients. We retrospectively evaluated seven IPA
      cases who were diagnosed among 207 patients that had undergone organ
      transplantation surgery in our center between 1998-2001. Of seven patients, four
      was renal and three was liver recipients. Diagnosis was made histopathologically
      (three post-mortem, one transbronchial lung biopsy) in four patients while
      culture positivity (sputum and tracheal aspiration material) with clinical and
      radiological evaluation was the diagnostic criteria for three patients. The most
      common respiratory symptoms were fever, productive cough and dyspnea. The most
      common fiberoptic bronchoscopic findings were mucosal fragility, hemorrhage. In
      one patient plaque formation was found. One liver recipients had been on
      hemodialysis because of renal insufficiency (serum creatine was 2.6 mg/dL). All
      liver and kidney recipients had allograft failure. One liver and two kidney
      recipients had neutropenia, two liver and one kidney recipients had
      thrombocytopenia. Six patients had received amphotericin-B and/or itraconazole
      therapy. Four of the five exitus were receiving antifungal treatment. Three of
      them were lost in a short time while only one non-survivor had received
      itraconazole for three weeks. The most frequent CT findings were patchy
      infiltrations and nodule formation with or without cavitation. Five patients were
      lost in two months (mortality, 71.4 %), two survivors are under follow up. These
      findings showed, IPA should be thought in the differential diagnosis of pulmonary
      infections after organ transplantation.

PMID- 15143426
TI  - [The features of cases of intrathoracic lymphomas].
AB  - In this study, 18 patients who had been diagnosed as intrathoracic lymphoma
      between January 1999 and August 2001 had been evaluated retrospectively to guide
      the diagnostic approaches. 12 (66.6%) of the patients were male and 6 (33.4%)
      were female. The mean age was 46.47 +/- 17.31. The leading symptoms were
      disapnea, cough, weight loss and fever. The most frequently seen laboratory
      findings were decreased hemoglobin and hematocrit rates (72.2%) and increased
      Lactate Dehydrogenase levels (44.4%). Radiologically, 18 (100%) patients had
      mediastinal lymph node enlargement, 8 (44.4%) patients had bilateral and 6
      (33.3%) had unilateral hilar enlargement, 3 (16.6%) patients had appearance of
      mass lesion, 1 (5.5%) had appearance of consolidation, 2 (11.1%) patients had
      atelectasis, 3 (16.6%) patients had appearance of pleural effusion.
      Histopathological diagnosis were undertaken with lymph node biopsies in 11(61.1%)
      patients, with bronchial biopsies in 2 (11.1%) patients, with pleural biopsy in 1
      (5.5%) patient, with lymph node and bronchial biopsies in 3 (16.6%) patients,
      with lymph node and pleural biopsies in 1 (5.5%) patient. 11 (61.1%) patients
      were diagnosed as Hodgkin Disease (nine as nodular type, two as mixed cellular
      type). 7 (38.9%) patients were diagnosed as non Hodgkin Lymphoma. After taking
      diagnosis the patients were sent to medical oncology clinics for follow up and
      therapy. These findings showed that different locations of intrathoracic
      lymphomas could be seen with nodal or extranodal presentations so it must be
      taken into account in differential diagnosis of other pathological conditions.

PMID- 15143427
TI  - Multiple endobronchial mass lesions due to sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease that primarily affects the lung
      and lymphatic systems of the body. The lungs are affected in over 90% of sarcoid
      patients. Although paranchymal lung disease is more common, the airways may also
      be involved. Bronchial mucosa is often affected in sarcoidosis, but endobronchial
      mass lesions are very rare. We present a case with multiple endobronchial mass
      lesions due to sarcoidosis.

PMID- 15143428
TI  - An unusual renal presentation of Wegener's granulomatosis.
AB  - A 63-year-old woman was admitted to our clinic with arthralgia, microhematuria
      and a pleural based solid mass in lower lobe basal segment of right lung seen in
      computerised tomogram of thorax. She was diagnosed as Wegener's granulomatosis by
      histopathological findings of right thoracotomy, wedge resection and
      decortication. The patient had positive antineutrophil cytoplasmic antibodies (c
      ANCA) in serum and tissue specimens. Histopathologic examination of the renal
      biopsy specimen revealed the diagnosis of tubulointerstitial nephritis. We report
      this case because of the unusual histologic type of renal involvement by
      reviewing the literature.

PMID- 15143429
TI  - [Hepatopulmonary syndrome].
AB  - Liver diseases affect lungs. Pulmonary vascular diseases are observed in hepatic
      diseases and portal hypertension have a wide spectrum that varies from
      intrapulmonary vascular dilatation to increased pulmonary vascular resistance
      with pulmonary hypertension. Hepatopulmonary syndrome is a syndrome characterized
      portal hypertension, intrapulmonary vascular dilatation and abnormal oxygenation
      (hypoxaemia). This review summarizes the clinicopathologic features, diagnostic
      criteria, and management of hepatopulmonary syndrome.

PMID- 15143430
TI  - [Metastatic lung tumours].

PMID- 15143431
TI  - [Upper airway resistance syndrome].
AB  - Upper Airway Resistance Syndrome (UARS) is characterized with daytime sleepiness
      and cardiovascular disturbances, because of the repetitive increase of upper
      airway resistance leading to arousals. UARS, can easily be overlooked because the
      conventional polysonographic measurements are not sensitive enough to diagnose
      this syndrome, therefore the prevalence and morbidity of this syndrome is not
      known. Measuring the increased inspiratory effort by an esophageal balloon during
      the rising upper airway resistance is the gold standard technique for the
      diagnosis. Treatment of UARS is similar with Obstructive Sleep Apnea Syndrome
      (OSAS). In this article the clinical picture, diagnosis, and management of the
      UARS is reviewed.

PMID- 15143432
TI  - Photosynthesis in a changing world.

PMID- 15143433
TI  - Direct and indirect climate change effects on photosynthesis and transpiration.
AB  - Climate change affects plants in many different ways. Increasing CO(2)
      concentration can increase photosynthetic rates. This is especially pronounced
      for C(3) plants, at high temperatures and under water-limited conditions.
      Increasing temperature also affects photosynthesis, but plants have a
      considerable ability to adapt to their growth conditions and can function even at
      extremely high temperatures, provided adequate water is available. Temperature
      optima differ between species and growth conditions, and are higher in elevated
      atmospheric CO(2). With increasing temperature, vapour pressure deficits of the
      air may increase, with a concomitant increase in the transpiration rate from
      plant canopies. However, if stomata close in response to increasing CO(2)
      concentration, or if there is a reduction in the diurnal temperature range, then
      transpiration rates may even decrease. Soil organic matter decomposition rates
      are likely to be stimulated by higher temperatures, so that nutrients can be more
      readily mineralised and made available to plants. This is likely to increase
      photosynthetic carbon gain in nutrient-limited systems. All the factors listed
      above interact strongly so that, for different combinations of increases in
      temperature and CO(2) concentration, and for systems in different climatic
      regions and primarily affected by water or nutrient limitations, photosynthesis
      must be expected to respond differently to the same climatic changes.

PMID- 15143434
TI  - Photosynthetic acclimation to simultaneous and interacting environmental stresses
      along natural light gradients: optimality and constraints.
AB  - There is a strong natural light gradient from the top to the bottom in plant
      canopies and along gap-understorey continua. Leaf structure and photosynthetic
      capacities change close to proportionally along these gradients, leading to
      maximisation of whole canopy photosynthesis. However, other environmental factors
      also vary within the light gradients in a correlative manner. Specifically, the
      leaves exposed to higher irradiance suffer from more severe heat, water, and
      photoinhibition stresses. Research in tree canopies and across gap-understorey
      gradients demonstrates that plants have a large potential to acclimate to
      interacting environmental limitations. The optimum temperature for photosynthetic
      electron transport increases with increasing growth irradiance in the canopy,
      improving the resistance of photosynthetic apparatus to heat stress. Stomatal
      constraints on photosynthesis are also larger at higher irradiance because the
      leaves at greater evaporative demands regulate water use more efficiently.
      Furthermore, upper canopy leaves are more rigid and have lower leaf osmotic
      potentials to improve water extraction from drying soil. The current review
      highlights that such an array of complex interactions significantly modifies the
      potential and realized whole canopy photosynthetic productivity, but also that
      the interactive effects cannot be simply predicted as composites of additive
      partial environmental stresses. We hypothesize that plant photosynthetic
      capacities deviate from the theoretical optimum values because of the interacting
      stresses in plant canopies and evolutionary trade-offs between leaf- and canopy
      level plastic adjustments in light capture and use.

PMID- 15143435
TI  - Diffusive and metabolic limitations to photosynthesis under drought and salinity
      in C(3) plants.
AB  - Drought and salinity are two widespread environmental conditions leading to low
      water availability for plants. Low water availability is considered the main
      environmental factor limiting photosynthesis and, consequently, plant growth and
      yield worldwide. There has been a long-standing controversy as to whether drought
      and salt stresses mainly limit photosynthesis through diffusive resistances or by
      metabolic impairment. Reviewing in vitro and in vivo measurements, it is
      concluded that salt and drought stress predominantly affect diffusion of CO(2) in
      the leaves through a decrease of stomatal and mesophyll conductances, but not the
      biochemical capacity to assimilate CO(2), at mild to rather severe stress levels.
      The general failure of metabolism observed at more severe stress suggests the
      occurrence of secondary oxidative stresses, particularly under high-light
      conditions. Estimates of photosynthetic limitations based on the photosynthetic
      response to intercellular CO(2) may lead to artefactual conclusions, even if
      patchy stomatal closure and the relative increase of cuticular conductance are
      taken into account, as decreasing mesophyll conductance can cause the CO(2)
      concentration in chloroplasts of stressed leaves to be considerably lower than
      the intercellular CO(2) concentration. Measurements based on the photosynthetic
      response to chloroplast CO(2) often confirm that the photosynthetic capacity is
      preserved but photosynthesis is limited by diffusive resistances in drought and
      salt-stressed leaves.

PMID- 15143436
TI  - Engineering plants for elevated CO(2): a relationship between starch degradation
      and sugar sensing.
AB  - In the future, plants will have additional CO(2) for photosynthesis. However,
      plants do not take maximal advantage of this additional CO(2) and it has been
      hypothesized that end product synthesis limitations and sugar sensing mechanisms
      are important in regulating plant responses to increasing CO(2). Attempts to
      increase end product synthesis capacity by engineering increased sucrose
      phosphate synthase activity have been generally, but not universally, successful.
      It was found that plants benefited from a two- to three-fold increase in SPS
      activity but a 10-fold increase did not increase yield. Despite the success in
      increasing yield, increasing SPS did not increase photosynthesis. However, carbon
      export from chloroplasts was increased during the day and reduced at night (when
      starch provides carbon for sucrose synthesis. We develop here a hypothesis that
      starch degradation is closely sensed by hexokinase because a newly discovered
      pathway required for starch to sucrose conversion that involves maltose is one of
      few metabolic pathways that requires hexokinase activity.

PMID- 15143437
TI  - Water shortage affects the water and nitrogen balance in Central European beech
      forests.
AB  - Whilst forest policy promotes cultivation and regeneration of beech dominated
      forest ecosystems, beech itself is a highly drought sensitive tree species likely
      to suffer from the climatic conditions prognosticated for the current century.
      Taking advantage of model ecosystems with cool-moist and warm-dry local climate,
      the latter assumed to be representative for future climatic conditions, the
      effects of climate and silvicultural treatment (different thinning regimes) on
      water status, nitrogen balance and growth parameters of adult beech trees and
      beech regeneration in the understorey were assessed. In addition, validation
      experiments with beech seedlings were carried out under controlled conditions,
      mainly in order to assess the effect of drought on the competitive abilities of
      beech. As measures of water availability xylem flow, shoot water potential,
      stomatal conductance as well as delta (13)C and delta (18)O in different tissues
      (leaves, phloem, wood) were analysed. For the assessment of nitrogen balance we
      determined the uptake of inorganic nitrogen by the roots as well as total N
      content and soluble N compounds in different tissues of adult and young trees.
      Retrospective and current analysis of delta (13)C, growth and meteorological
      parameters revealed that beech growing under warm-dry climatic conditions were
      impaired in growth and water balance during periods with low rain-fall. Thinning
      affected water, N balance and growth mostly of young beech, but in a different
      way under different local climatic conditions. Under cool, moist conditions,
      representative for the current climatic and edaphic conditions in beech forests
      of Central Europe, thinning improves nutrient and water status consistent to
      published literature and long-term experience of forest practitioners. However,
      beech regeneration was impaired as a result of thinning at higher temperatures
      and under reduced water availability, as expected in future climate.

PMID- 15143438
TI  - Interaction of flooding with carbon metabolism of forest trees.
AB  - Waterlogging and flooding cause oxygen deprivation in the root system of trees.
      Since oxygen is essentially for mitochondrial respiration, this process cannot be
      maintained under anoxic conditions and must be replaced by other pathways. For
      the roots it is therefore a matter of survival to switch from respiration to
      alcoholic fermentation. Due to the low efficiency of this process to yield energy
      equivalents (ATP), energy and carbon metabolism of trees are usually strongly
      affected by oxygen deprivation, even if a rapid switch from respiration to
      fermentation is achieved. The roots can compensate for the low energy yield of
      fermentation either (1) by decreasing the demand for energy by a reduction of
      energy-dependent processes such as root growth and/or nutrient uptake, or (2) by
      consuming more carbohydrates per unit time in order to generate sufficient energy
      equivalents. In the leaves of trees, flooding and waterlogging cause a decline in
      the rates of photosynthesis and transpiration, as well as in stomatal
      conductance. It is assumed that, due to reduced phloem transport, soluble sugars
      and starch accumulate in the leaves of flooded trees, thereby negatively
      affecting the sugar supply of the roots. Thus, root growth and survival is
      negatively affected by both changes in root internal carbon metabolism and
      impaired carbon allocation to the roots by phloem transport. In addition,
      accumulation of toxic products of fermentation in the roots, such as
      acetaldehyde, can further impair root metabolism. A main feature of tolerance
      against flooding and waterlogging of trees seems to be the steady supply of
      carbohydrates to the roots in order to maintain alcoholic fermentation; in
      addition, roots of tolerant trees seem to avoid accumulation of fermentation
      derived ethanol and acetaldehyde. From studies with flooding tolerant and non
      tolerant tree species, it is hypothesized that (1) the transport of ethanol
      produced in the roots under hypoxic conditions into the leaves via the
      transpiration stream, (2) its conversion into acetyl-CoA in the leaves, and (3)
      its use in the plant's general metabolism, are mechanisms of flooding tolerance
      of trees.

PMID- 15143439
TI  - Development of leaf photosynthetic parameters in Betula pendula Roth leaves:
      correlations with photosystem I density.
AB  - The global modelling of photosynthesis is based on exact knowledge of the leaf
      photosynthetic machinery. The capacities of partial reactions of leaf
      photosynthesis develop at different rates, but it is not clear how the
      development of photoreactions and the Calvin cycle are co-ordinated. We
      investigated the development of foliar photosynthesis in the temperate deciduous
      tree Betula pendula Roth. using a unique integrated optical/gas exchange
      methodology that allows simultaneous estimation of photosystem I and II (PS I and
      PS II) densities per leaf area, interphotosystem electron transport activities,
      and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) kinetic properties.
      We combined these measurements with in vitro determinations of Rubisco, soluble
      protein and chlorophyll contents. We observed a strong increase in leaf
      photosynthetic capacity in developing leaves per leaf area, as well as per dry
      mass, that was paralleled by accumulation of leaf Rubisco. Enhanced mesophyll
      conductance was the outcome of increased carboxylation capacity and increased
      CO(2) diffusion conductance. However, Rubisco was only partly activated in the
      leaves, according to in vivo measurements of Rubisco kinetics. The amount of
      active Rubisco increased in proportion with development of PS I, probably through
      a direct link between Rubisco activase and PS I electron transport. Since the
      kinetics for post-illumination P700 re-reduction did not change, the synthesis of
      cytochrome b(6)f complex was also proportional to PS I. The synthesis of PS II
      began later and continued for several days after reaching the full PS I activity,
      but leaf chlorophyll was shared equally between the photosystems. Due to this,
      the antenna of PS II was very large and not optimally organized, leading to
      greater losses of excitation and lower quantum yields in young leaves. We
      conclude that co-ordinated development of leaf photosynthesis is regulated at the
      level of PS I with subordinated changes in PS II content and Rubisco activation.

PMID- 15143440
TI  - Thermoluminescence study of photosystem II activity in Haberlea rhodopensis and
      spinach leaves during desiccation.
AB  - Thermoluminescence glow curve parameters were used to access the functional
      features of PS II in the Balkan endemic Haberlea rhodopensis. This representative
      of the higher desiccation-tolerant plants is unique for the European flora. An
      unusual high temperature of TL emission from Haberlea leaves after excitation by
      one flash at 5 degrees C was observed. The position of the main TL B band (S (2)Q
      (B)(-)) was at 45 - 47 degrees C, while this temperature was 30 - 32 degrees C in
      drought-sensitive mesophytic spinach. Consistent with the up-shift in TL
      emission, the lifetime of the S (2) state was also increased, showing a
      stabilization of charge storage in PS II complex in this resurrection plant. In
      addition, a part of PS II centres was less susceptible to DCMU. We consider the
      observed unusual TL characteristics of Haberlea rhodopensis reflect some
      structural modifications in PS II (especially in D1 protein), which could be
      related to the desiccation tolerance of this plant. This suggestion was supported
      by the different manner in which dehydration affected the TL properties in
      desiccation-tolerant Haberlea and desiccation-sensitive spinach plants.

PMID- 15143441
TI  - Role of red carotenoids in photoprotection during winter acclimation in Buxus
      sempervirens leaves.
AB  - The red leaf coloration of several plant species during autumn and winter is due
      to the synthesis of phenolic compounds such as anthocyanins or red carotenoids.
      The latter occur very rarely and are non-ubiquitous and taxonomically restricted
      compounds. The present study shows that the leaves of common box ( Buxus
      sempervirens L.) accumulate red carotenoids (eschscholtzxanthin,
      monoanhydroeschscholtzxanthin, anhydroeschscholtzxanthin) as a response to
      photoinhibitory conditions during winter acclimation. These compounds are
      produced in a coordinated manner with the operation of other photoprotective
      systems: accumulation and sustained deepoxidation of VAZ pigments with a
      concomitant decrease in maximal photochemical efficiency, accumulation of alpha
      tocopherol and a gradual decrease on chlorophyll content. All these processes
      were reversed when the photosynthetic tissues were transferred from
      photoinhibitory winter conditions to room temperature for 9 days. Buxus leaves
      showed a large degree of phenotype variation in the degree of reddening, ranging
      from green to orange. The differences in colour pattern were mainly due to
      differences in the accumulation of red carotenoids and xanthophyll esters. Red
      pigments were mainly anhydroeschscholtzxanthin and esters of eschscholtzxanthin.
      Conversely to fruit or petal chromoplasts, the plastids of red leaves in this
      species are not the terminal differentiated state but are able to redifferentiate
      again to chloroplasts. Their photoprotective role during winter as a light screen
      system or as antioxidants, in a similar way to other red pigments, and their
      implications on the wide ecological tolerance of this evergreen species are
      discussed.

PMID- 15143442
TI  - High-light stress and photoprotection in Umbilicaria antarctica monitored by
      chlorophyll fluorescence imaging and changes in zeaxanthin and glutathione.
AB  - The effect of high light on spatial distribution of chlorophyll (Chl)
      fluorescence parameters over a lichen thallus (Umbilicaria antarctica) was
      investigated by imaging of Chl fluorescence parameters before and after exposure
      to high light (1500 micro mol m (-2) s (-1), 30 min at 5 degrees C). False colour
      images of F (V)/F (M) and Phi (II) distribution, taken over thallus with 0.1 mm
      (2) resolution, showed that maximum F (V)/F (M) and Phi (II) values were located
      close to the thallus centre. Minimum values were typical for thallus margins.
      After exposure to high light, a differential response of F (V)/F (M) and Phi (II)
      was found. The marginal thallus part exhibited a loss of photosynthetic activity,
      manifested as a lack of Chl fluorescence signal, and close-to-centre parts showed
      a different extent of F (V)/F (M) and Phi (II) decrease. Subsequent recovery in
      the dark led to a gradual return of F (V)/F (M) and Phi (II) to their initial
      values. Fast (30 min) and slow (1 - 22 h) phase of recovery were distinguished,
      suggesting a sufficient capacity of photoprotective mechanisms in U. antarctica
      to cope with low-temperature photoinhibition. Glutathione and xanthophyll cycle
      pigments were analyzed by HPLC. High light led to an increase in oxidized
      glutathione (GSSG), and a conversion of violaxanthin to zeaxanthin, expressed as
      their de-epoxidation state (DEPS). The responses of GSSG and DEPS were reversible
      during subsequent recovery in the dark. GSSG and DEPS were highly correlated to
      non-photochemical quenching (NPQ), indicating involvement of these antioxidants
      in the resistance of U. antarctica to high-light stress. Heterogeneity of Chl
      fluorescence parameters over the thallus and differential response to high light
      are discussed in relation to thallus anatomy and intrathalline distribution of
      the symbiotic alga Trebouxia sp.

PMID- 15143443
TI  - The xanthophyll cycle in green algae (chlorophyta): its role in the
      photosynthetic apparatus.
AB  - Light-dependent conversion of violaxanthin to zeaxanthin, the so-called
      xanthophyll cycle, was shown to serve as a major, short-term light acclimation
      mechanism in higher plants. The role of xanthophylls in thermal dissipation of
      surplus excitation energy was deduced from the linear relationship between
      zeaxanthin formation and the magnitude of non-photochemical quenching. Unlike in
      higher plants, the role of the xanthophyll cycle in green algae (Chlorophyta) is
      ambiguous, since its contribution to energy dissipation can significantly vary
      among species. Here, we have studied the role of the xanthophyll cycle in the
      adaptation of several species of green algae (Chlorella, Scenedesmus,
      Haematococcus, Chlorococcum, Spongiochloris) to high irradiance. The xanthophyll
      cycle has been found functional in all tested organisms; however its contribution
      to non-photochemical quenching is not as significant as in higher plants. This
      conclusion is supported by three facts: (i) in green algae the content of
      zeaxanthin normalized per chlorophyll was significantly lower than that reported
      from higher plants, (ii) antheraxanthin + zeaxanthin content displayed different
      diel kinetics from NPQ and (iii) in green algae there was no such linear
      relationship between NPQ and Ax + Zx, as found in higher plants. We assume that
      microalgae rely on other dissipation mechanism(s), which operate along with
      xanthophyll cycle-dependent quenching.

PMID- 15143444
TI  - Water sources and water-use efficiency in mediterranean coastal dune vegetation.
AB  - In coastal environments plants have to cope with various water sources:
      rainwater, water table, seawater, and mixtures. These are usually characterized
      by different isotopic signatures ( (18)O/ (16)O and D/H ratios). Xylem water
      reflects the isotopic compositions of the water sources. Additionally, water-use
      efficiency (WUE) can be assessed with carbon isotope discrimination (Delta)
      analyses. Gas exchange, Delta of leaf dry matter, and isotopic composition (delta
      (18)O) of xylem water were measured from June to August 2001 in herbaceous
      perennials of mobile dunes (Ammophila littoralis, Elymus farctus) and
      sclerophyllous shrubs and climbers (Arbutus unedo, Pistacia lentiscus, Phillyrea
      angustifolia, Qercus ilex, Juniperus oxycedrus, Smilax aspera) of consolidated
      dunes. Assimilation rates were rather low and did not show clear seasonal
      patterns, possibly due to limited precipitation and generally low values of
      stomatal conductance. The lowest values were shown in S. aspera. Different
      physiological patterns were found, on the basis of delta (18)O and Delta
      analyses. Values of delta (18)O of xylem water of phanerophytes were remarkably
      constant and matched those of the water table, indicating dependence on a
      reliable water source; values of Delta were relatively high, indicating low
      intrinsic WUE, with the exception of J. oxycedrus. Surprisingly, very high delta
      (18)O values were found for the xylem water from S. aspera in August. This
      suggests retrodiffusion of leaf water to xylem sap in the stem or direct uptake
      of water by leaves or stems, owing to dew or fog occurrence. Low Delta values
      indicated high WUE in S. aspera. Contrasting strategies were shown by the species
      of mobile dunes: E. farctus relied on superficial water and exhibited low WUE,
      accordingly to its therophyte-like vegetative cycle; on the contrary, A.
      littoralis used deeper water sources, showing higher WUE in relation to its long
      lasting vegetative habit.

PMID- 15143445
TI  - Hg(2+) reacts with different components of the NADPH : protochlorophyllide
      oxidoreductase macrodomains.
AB  - The molecular background of Hg (2+)-induced inhibition of protochlorophyllide
      (Pchlide) photoreduction was investigated in homogenates of dark-grown wheat
      leaves. Our earlier work showed that 15 min incubation with 10 (-2) M Hg (2+)
      completely inhibits the activity of NADPH : Pchlide oxidoreductase ( ). Detailed
      analysis of spectra recorded at 10 K indicated the appearance of emission bands
      at 638 and 650 nm, which are characteristic for NADP (+)-Pchlide complexes.
      Fluorescence emission spectra recorded with different excitation wavelengths,
      fluorescence lifetime measurements and the analysis of acetone extractions
      revealed that Hg (2+) can also react directly with Pchlide, resulting in
      protopheophorbide formation. At 10 (-3) M Hg (2+), the phototransformation was
      complete but the blue shift of the chlorophyllide emission band speeded up
      remarkably. This indicates oxidation of the NADPH molecules that have a
      structural role in keeping together the etioplast inner membrane components. We
      suggest a complex model for the Hg (2+) effect: depending on concentration it can
      react with any components of the NADPH : Pchlide oxidoreductase macrodomains.

PMID- 15143446
TI  - [Erythropoietin in patients with head and neck carcinomas?].
AB  - BACKGROUND: Various studies have demonstrated the prognostic significance of the
      pretherapeutic blood hemoglobin concentration for patients with head and neck
      cancer following surgery or primary definitive or adjuvant radio- or
      radiochemotherapy. It was the aim of this study to evaluate whether the prognosis
      of these patients might be improved when correcting decreased pretherapeutic
      hemoglobin values by administering erythropoietin. METHOD: In a prospective
      placebo-controlled double-blind study (Cochrane "evidence-based medicine" level
      Ib) the effect of erythropoietin was analyzed in patients with locally advanced
      head or neck tumours with low blood hemoglobin values (women: < 12 g/dL; men: <
      13 dL) and a Karnofski value of > 60 following primary definite or adjuvant
      radiotherapy (up to 70 Gy). The time to local tumour progression and survival was
      evaluated. Kaplan-Maier estimates were applied and, the relative risk of well
      known prognostic factors tested for with a Cox Proportional Hazards model.
      RESULTS: 157 patients of the Freiburg University ENT-clinic were recruited from
      1997 to 2001. Study conduct was performed according to the GCP guidelines. A
      rapid increase of the blood hemoglobin value happened during the first five weeks
      of treatment under epoetin beta. Placebo patients experienced only minor changes
      of the hemoglobin value. Following adjuvant radiotherapy local tumour control
      probability at two years was 68 % +/- 7 % and 72 +/- 7 % for placebo and epoetin
      beta patients, respectively (p = 0.64). Patients who had undergone primary
      definite radiation experienced a local control probability of 36 % +/- 11 % in
      the placebo arm after two years, compared to epoetin beta with 23 % +/- 11 % (p =
      0.05). CONCLUSION: Epoetin beta resulted in prompt and stable correction of blood
      hemoglobin values in anemic patients with advanced head or neck tumours, but
      tumour control and survival was impaired particularly in patients with a high
      tumour burden.

PMID- 15143447
TI  - [Does computer-aided navigation of endonasal sinus surgery improve process
      quality and outcome quality?].
AB  - BACKGROUND: Ever since navigation technology was introduced into endonasal
      surgery, its impact on process and result of surgery has been debated. In this
      respect, factors of investment costs and additional costs for time exposure will
      be discussed as well. PATIENTS AND METHODS: In a retrospective analysis of
      quality assurance, the results of endonasal surgery by surgeons of different
      experience in 56 patients were evaluated. Preparation time, preoperative setup
      time as well as time of actual surgery were analysed and compared with possible
      indications for navigation. RESULTS: From our analysis a classification resulted
      dividing the indications for navigation into the following four different
      categories: redundant, reasonable, helpful, necessary. Navigation was redundant
      when it was dispensable and did not result in a clear improvement of process or
      outcome quality. Navigation has been proved reasonable when it helped to obtain
      additional information for improving process quality. It was considered helpful
      when the information obtained by navigation had an influence at least on the
      course and/or result of surgery. Navigation was necessary from the surgeon's
      point of view when the intervention in regard to the benefit-risk-ratio could not
      be justified without navigation, or only intraoperative slice imaging would allow
      surgery. CONCLUSION: Not only redundant, but also facultative and obligatory
      indications for navigation in endonasal surgery result from careful consideration
      of the risk-benefit-cost ratio. In standardized endonasal sinus surgery, like
      infundibulotomy or ethmoidectomy, however, navigation can be a hindrance to
      process quality and does not result in any advantage for outcome quality.

PMID- 15143448
TI  - [Extranasopharyngeal angiofibroma of the nasal cavity and paranasal sinuses].
AB  - BACKGROUND: Angiofibromas commonly arise in the nasopharynx in young male
      patients. Diagnosis is widely based on radiographic imaging to avoid ill-advised
      biopsy which may result in brisk bleeding. This study was undertaken to evaluate
      the incidence, clinical features and complications that may occur during the
      process of diagnosis and surgical therapy of angiofibromas outside the
      nasopharynx. METHODS AND PATIENTS: Case report of a 13-year-old female patient
      and review of the literature. RESULTS: Our patient received multi-agent
      chemotherapy elsewhere due to a misdiagnosed angiofibroma. Computed Tomography
      (CT) revealed a maxillary tumor which was repeatedly biopsied. Hypervascularity
      was excluded by arteriography and the lesion removed after lateral rhinotomy. The
      data of 42 patients were analyzed including our own case. 32 patients were male,
      10 female. The majority became symptomatic aged 19 years or younger (71.4 %). The
      maxilla was most commonly affected (38 %), less frequently the ethmoid, nasal
      cavity or septum, beside others. In 38 patients, symptoms developed within 12
      months or less (average: 8.5 months). Epistaxis, nasal obstruction and facial
      swelling were reported for most patients. Brisk bleeding occurred in 10 patients
      during tumor removal and resulted from biopsies in 11 of 20 patients. Angiography
      detected hypervascularity in 3 of 4 patients. There was no case with lethal
      outcome. CONCLUSION: Extranasopharyngeal angiofibromas of the nasal cavity or
      paranasal sinuses should be included in the differential diagnosis of nasal
      tumors. Compared to nasopharyngeal angiofibromas, more female patients are
      involved, symptoms develop more quickly but hypervascularity is less common.
      Signs of questionable hypervascularity in Computed Tomography and Magnetic
      Resonance Imaging (MRI) should indicate arteriography prior to surgical
      procedures. Preoperative embolization of hypervascular lesions during
      arteriography will reduce the risk of brisk bleeding during biopsy or surgical
      tumor removal.

PMID- 15143449
TI  - [Aminoglycoside- and cisplatin-ototoxicity: from basic science to clinics].
AB  - Gentamicin and cisplatin are clinically widely used pharmacological agents which
      may induce irreversible hearing loss as a side effect. Concerning the
      pathomechanisms of ototoxicity as well as preventive strategies there are
      similarities but also some differences. In this review we focus on the role of
      reactive oxygen species, the antioxidant system, cellular iron and calcium as
      well as nitric oxide and neurotrophins on gentamicin- and cisplatin-ototoxicity.
      Furthermore we deal with apoptotic and necrotic cell death as well as the role of
      mitochondria in these cell injury processes.

PMID- 15143450
TI  - [Conservative treatment in mild obstructive sleep apnea: comparison of
      theophylline and nasal continous positive airway pressure ventilation].
AB  - BACKGROUND: Comparison of theophylline and nasal continous positive airway
      pressure-ventilation (nCPAP) in patients non eligible for surgical treatment with
      obstructive sleep apnea. PATIENTS AND MATERIALS: In a prospective non-randomized
      study 60 patients with mild obstructive sleep apnea were investigated. All
      individuals were not eligible for surgery under general anaesthesia or refused
      surgical treatment. The efficacy of a daily single dose oral theophylline (5 - 7
      mg/kg body weight, n = 30) and nCPAP ventilation (n = 30) was evaluated by apnea
      hypopnea index (AHI) and Epworth Sleepiness Scale (ESS). Statistical data
      analysis was performed using the Wilcoxon-Test. RESULTS: In the theophylline
      group 4/26 patients (15 %) showed a mean AHI reduction of 42 %. The ESS-Score
      improved from 10.0 to 8.0. Therapy compliance was 86 %. The non-responder (22/26
      patients, 85 %) group showed a mean AHI increase of 11 % (from 24.6 to 27.3).
      This difference was not of statistical significance (p < or = 0.878). In the CPAP
      group the AHI decreased from 23.3 to 2.9 (p < or = 0,0001). Mean ventilation
      pressure was 6.4 mbar. The ESS-Score improved from 10 to 8. Compliance was 50 %.
      Six of thirty patients (20 %) did not use the CPAP device regularly. During the
      first four weeks another nine of thirty (30.7 %) patients turned back the device.
      Main reasons were discomfort (61 %), noise (38 %), rhinitis, conjunctivitis and
      discomfort of the partner (10 %). CONCLUSIONS: None of the treatments
      investigated can be considered as a substantial alternative for the majority of
      patients non eligible for surgery. Theophylline has a high compliance but little
      therapeutic effect. CPAP-ventilation is more effective but has a compliance
      problem in the patients investigated. Both modalities may have benefit but have
      to be individually indicated. A multimodal approach may ease the problem.

PMID- 15143451
TI  - [The interesting case - case no. 60. Fibrolipoma of the parapharyngeal region].
AB  - Tumours of the parapharyngeal region represent 0.5 % of all head and neck
      tumours. Most of them are benign and derive from the salivary gland tissue or
      have neurogenic offspring (neurolemmoma and paraganglioma). Fibrolipoma of the
      parapharyngeal space are extremely rare. There are only case reports found
      occasionally in the literature. We report about case of fibrolipoma in the
      parapharyngeal space of a 65-years-old man. Symptoms, diagnostic, differential
      diagnostic, as well as treatment will be discussed in context with the
      international literature.

PMID- 15143452
TI  - [Prevention and treatment of metabolic syndrome and diabetes. Medical and
      political responsibility for the health of the next generation].

PMID- 15143453
TI  - [Autoantibodies against islet cell antigens and type 1 diabetes after treatment
      with interferon-alpha].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to study the appearance of
      autoantibodies against islet cells and the development of type 1 diabetes in
      patients with chronic hepatitis C during interferon treatment. PATIENTS AND
      METHODS: 74 patients (24 women, 50 men, mean age: 46 years) with HCV infection
      were treated with interferon, ribavirin and amantadin versus placebo, after they
      had failed to previous interferon therapy in a prospective, randomised trial. At
      the end of treatment period anti-islet cell autoantibodies (anti-GAD, anti IA-2),
      anti-insulin antibodies, TSH, anti-thyroid autoantibodies (TPO, thyreoglobulin,
      TSH-receptor antibodies) were measured. RESULTS: In two patients, GAD
      autoantibodies were found, but both patients were negative for IA-2 and insulin
      antibodies. One of the patients developed type 1 diabetes five months after start
      of treatment. In this patient, the anti-GAD titer was initial 0 U/ml (normal: <
      1.2). The titer raised to 52,2 U/ml after the interferon monotherapy. During the
      second interferon treatment (in combination) the titer raised from initial 41,1
      U/ml to 59,6 U/ml. The anti-GAD titer of the second patient was 0 U/ml before
      treatment and raised to 1,7 U/ml. This patient did not develop a type 1 diabetes.
      CONCLUSION: Type 1 diabetes is a rare but serious complication of interferon
      therapy. Repetitive treatment seems to facilitate this complication. Screening
      for islet antibodies before a second therapy could be useful.

PMID- 15143454
TI  - [Transition clinics in endocrinology and diabetology for the chronically ill in
      Germany. A recent inquiry].
AB  - BACKGROUND AND OBJECTIVES: Transferring adolescent patients with endocrine
      disorders from paediatric to adult care units depends on regional facilities with
      varying efficiency. A nationwide system of transition clinics in Germany is
      actually not available, despite demands by physicians and patients. PATIENTS AND
      METHODS: We conducted a survey for the 36 German university hospitals to examine
      the regional existence and characteristics of actual transition methods. In a
      second questionnaire patients were asked to report their individual transition
      periods. RESULTS: Despite physician's demand in the majority of hospitals, there
      are only eight transition clinics nationwide. On average 56 patients attended
      these clinics yearly. Most patients suffered from disorders of pituitary, thyroid
      or adrenal gland (each 76 %) and diabetes mellitus type 1 (82 %). The perception
      of teamwork between the paediatric and adult care units was better in hospitals
      with transition clinics. Moreover, there was more scientific cooperation in those
      hospitals. Attendance to medical care and patient's compliance was enhanced by
      establishing transition clinics in 82 % and 70 %, respectively. Questioning
      affected patients we found attendance to the paediatric team up to the age of
      twenty with substantial difficulties finding an adequate adult care unit.
      Patients were more contend with paediatric than adult quality of physicians care
      (mark 1.6 versus 2.4). 82 % of patients judged establishing transition clinics as
      "urgently needed". CONCLUSION: In conclusion there are transition clinics in one
      quarter of German university hospitals. A more widespread installation of
      transition clinics is medical reasonable and is demanded by patients.

PMID- 15143455
TI  - [Diabetes in childhood: everyday burden and professional consequences for
      parents].
AB  - BACKGROUND AND OBJECTIVE: To investigate the burden and the financial and
      professional consequences for mothers and fathers after the onset of diabetes in
      their child in relationship to age at onset and family structure. PATIENTS AND
      METHODS: All families of children with an age at onset < 14 years and a diabetes
      duration < 10 years treated at four large pediatric diabetes centers received a
      structured questionnaire (burden of diabetes, professional position and career
      development, financial consequences for both parents, demographic data). RESULTS:
      580 families with 583 children with type 1 diabetes (46 % girls, diabetes
      duration 5.0 +/- 3.2 years, age at onset 6.9 +/- 3.9 years) participated. 42 % of
      the children had an age at onset below 6 years. 11 % had single parents. Before
      the onset of diabetes in their children 93 % of the fathers worked full-time,
      thereafter 4 % changed their employment. Mothers worked at onset full-time in 22
      % and part-time in 38 %; thereafter 31 % reduced their working time or stopped
      working. 33 % of the mothers reported handicaps in their professional career
      development, especially those with a child with age at onset below 6 years (44
      %). Negative financial consequences were present in 44 % of the families. The day
      to day burden on a scale from 1 to 5 decreased both in mothers and in fathers
      with increasing age at onset. The individual burden was higher in mothers (3.6 +/
      1.1) than in fathers (2.8 +/- 1.1) (p = 0.000). CONCLUSIONS: Initiatives to
      reduce the burden on families with a child with diabetes are urgently needed.
      Particularly the social and professional integration of mothers with younger
      children at diabetes onset need to be improved through support measures outside
      the family.

PMID- 15143456
TI  - [Hypoglycemia and transient diabetes mellitus in an insulin autoimmune syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 53-year-old Caucasian woman presented with
      repeated episodes of hypoglycemia. Self-monitored blood glucose levels during the
      attacks were between 40 and 60 mg/dl (2.2-3.3 mmol/l). INVESTIGATIONS: An oral
      glucose tolerance test performed over 210 minutes showed normal baseline glucose
      levels, markedly elevated levels of serum insulin and slightly elevated C-peptide
      concentrations. During the test, a marked increase of insulin and a normal
      increment of C-peptide were observed. The tentative diagnosis of an insulinoma
      was raised and a 72 h fasting test performed, throughout which the insulin
      glucose-ratio was pathologically elevated, whereas C-peptide levels were only
      slightly elevated. DIAGNOSIS: Strongly positive levels of insulin antibodies led
      to the diagnosis of an insulin autoimmune syndrome. TREATMENT AND COURSE: This
      syndrome is caused by IgG-insulin-complexes with prolonged plasma half-life in
      the presence of reduced insulin action. The therapy consisted of fractionated
      meals to avoid hyperinsulinism and following hypoglycemic episodes. After four
      months a spontaneous clinical remission was observed. CONCLUSION: The autoimmune
      insulin syndrome is a rare cause of recurrent, spontaneous hypoglycemia in Europe
      in non diabetic patients. Its prognosis is good as there is a high rate of
      spontaneous clinical remission in up to 80 % of patients.

PMID- 15143457
TI  - [Diabetes-associated autoimmune disease in children and juveniles: how important
      is early recognition?].
AB  - Coeliac disease (CD) and autoimmune thyreoiditis (AIT) are associated with type-1
      diabetes. These diseases frequently occur without apparent clinical symptoms.
      Therefore, a serological screening by autoantibody testing is required for early
      detection. Identified by screening, the prevalence of CD and AIT is reported to
      be up to 10-fold higher in young patients with type-1 diabetes than in healthy
      children. Up to now, no uniform recommendations exist regarding a standardized
      screening procedure as well as the treatment of patients with clinically
      asymptomatic disorder and evidence of autoimmunity. A delay in the detection of
      associated diseases, however, may lead to clinical relevant, but otherwise
      preventable complications.

PMID- 15143458
TI  - [Insulin pump treatment in type 1 diabetes mellitus].

PMID- 15143459
TI  - [Cardioprotection by acarbose--pro].

PMID- 15143460
TI  - [Cardioprotection by acarbose--contra].

PMID- 15143461
TI  - Involvement of secreted Aspergillus fumigatus proteases in disruption of the
      actin fiber cytoskeleton and loss of focal adhesion sites in infected A549 lung
      pneumocytes.
AB  - Aspergillus fumigatus is an opportunistic pathogenic fungus that predominantly
      infects the respiratory system. Penetration of the lung alveolar epithelium is a
      key step in the infectious process. The cytoskeleton of alveolar epithelial cells
      forms the cellular basis for the formation of a physical barrier between the
      cells and their surroundings. This study focused on the distinct effects of A.
      fumigatus on the actin cytoskeleton of A549 lung pneumocytes. Of the 3 major
      classes of cytoskeletal fibers--actin microfilaments, microtubules, and
      intermediate filaments--only the actin cytoskeleton was found to undergo major
      structural changes in response to infection, including loss of actin stress
      fibers, formation of actin aggregates, disruption of focal adhesion sites, and
      cell blebbing. These changes could be specifically blocked in wild-type strains
      of A. fumigatus by the addition of antipain, a serine and cysteine protease
      inhibitor, and were not induced by an alkaline serine protease-deficient strain
      of A. fumigatus. Antipain also reduced, by approximately 50%, fungal-induced A549
      cell detachment from the plates and reduction in viability. Our findings suggest
      that A. fumigatus breaches the alveolar epithelial cell barrier by secreting
      proteases that act together to disorganize the actin cytoskeleton and destroy
      cell attachment to the substrate by disrupting focal adhesions.

PMID- 15143462
TI  - A proof-of-concept study of short-cycle intermittent antiretroviral therapy with
      a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment
      of chronic HIV infection.
AB  - BACKGROUND: We previously demonstrated that short-cycle structured intermittent
      therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral
      therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen
      maintained suppression of plasma HIV viremia while reducing serum levels of
      lipids. Adherence to such a regimen may be problematic for certain patients.
      METHODS: Eight patients with a history of receiving combination ART that
      maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily
      SIT regimen of didanosine, lamivudine, and efavirenz. RESULTS: For 7 patients,
      suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks.
      Four patients with adequate samples had no evidence for an increase in plasma
      viremia for up to 72 weeks, by use of an assay with a limit of detection of <1
      copy/mL. The lack of rebound viremia may be the result of the persistence of
      efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7
      patients. There was no significant change in CD4(+) T cell counts or serum
      hepatic transaminase or lipid levels. CONCLUSION: A once-daily short-cycle SIT
      regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell
      counts. Such a regimen may have importance in resource-limited settings where the
      monetary cost of continuous ART is prohibitive.

PMID- 15143463
TI  - Minor mutations in HIV protease at baseline and appearance of primary mutation
      90M in patients for whom their first protease-inhibitor antiretroviral regimens
      failed.
AB  - The association between minor mutations in human immunodeficiency virus (HIV)
      protease at baseline and development of common primary mutation 90M at
      virological failure (conferring some resistance to all protease inhibitors [PIs])
      was evaluated in 93 previously drug-naive patients experiencing failure of their
      first PI-based antiretroviral regimens. In logistic regression analysis, the
      probability of accumulating a new 90M mutation at virological failure was
      associated with the presence at baseline of minor mutation 36I (naturally
      occurring in approximately 25% of HIV clade B and in >80% of HIV non-clade-B
      viruses) (adjusted odds ratio, 13.5 [95% confidence interval, 1.89-95.6]; P=.009)
      and, possibly, of 10I/V. This suggests a potential role for the presence of 36I
      at baseline in predicting the appearance of 90M at virological failure.

PMID- 15143464
TI  - Prospective analyses of HIV-1-specific proliferative responses, recall antigen
      proliferative responses, and clinical outcomes in an HIV-1-seropositive cohort.
AB  - BACKGROUND: In cross-sectional studies of chronically infected individuals,
      lymphoproliferative responses to human immunodeficiency virus (HIV) type 1 p24
      Gag antigen have previously been associated with lower virus load. It was not
      known whether this association would be predictive of better clinical outcome in
      longitudinal studies. METHODS: In blood samples from 608 HIV-seropositive
      individuals enrolled in a trial of glycoprotein 160 vaccine therapy over the
      course of 3-5 years, lymphoproliferative responses to HIV-1 antigens, tetanus
      toxoid (TT), and mitogens were measured and correlated with clinical outcome and
      other parameters of progression. Baseline lymphoproliferative responses to
      antigens and mitogens were used to categorize the cohort into responders or
      nonresponders. RESULTS: Although response to recall antigens did not correlate
      with clinical indices of disease progression, positive baseline
      lymphoproliferative responses to p24 and TT were associated with lower plasma
      levels of HIV-1 RNA. Persistently positive lymphoproliferative responses to the
      antigens also inversely correlated with repeated measurements of virus load,
      although the significance was lost once the measurements were adjusted for virus
      load and CD4(+) cell count at baseline, by use of generalized estimating equation
      analysis. CONCLUSIONS: These observations suggest that the effect of the
      association between lymphoproliferative response and virus load is established
      early during HIV-1 infection and does not increase over time and suggest that
      antigen-specific lymphoproliferative responses reflect the dynamic state of HIV-1
      infection and are inversely associated with virus load.

PMID- 15143465
TI  - Gender as a risk factor for both antibiotic resistance and infection with
      pediatric serogroups/serotypes, in HIV-infected and -uninfected adults with
      pneumococcal bacteremia.
AB  - Among 1022 adults with either pneumococcal bacteremia or meningitis, 85.5% of
      women and 74.7% of men were infected with human immunodeficiency virus (HIV). A
      multivariable regression analysis found more pediatric serogroups/serotypes (odds
      ratio [OR], 1.59 [95% confidence interval [CI], 1.18-2.15]) and more penicillin
      nonsusceptible strains (OR, 1.65 [95% CI, 1.06-2.59]) in women than in men; it
      was also found that bacteremic women were more likely to be infected with HIV
      (OR, 1.85 [95% CI, 1.26-2.71]) and to be younger (OR, 1.72 [95% CI, 1.25-2.36])
      than were men. Thus, conjugate pneumococcal vaccination of children may reduce,
      in particular, both antibiotic resistance and the burden of conjugate vaccine
      serotype pneumococcal disease in young, HIV-infected women.

PMID- 15143467
TI  - Body-composition changes in the simian immunodeficiency virus-infected juvenile
      rhesus macaque.
AB  - BACKGROUND: Body-composition changes are common in individuals infected with
      human immunodeficiency virus. The purpose of the present study was to measure, as
      a model of wasting in acquired immunodeficiency syndrome (AIDS), longitudinal
      body-composition changes in macaques infected with simian immunodeficiency virus
      (SIV). METHODS: Twelve juvenile macaques were inoculated with SIVmac239.
      Immunologic, virologic, somatometric, and dual-energy x-ray-absorptiometry
      measurements were performed prospectively every 4 weeks for 72 weeks and were
      compared to measurements taken from 8 uninfected control macaques. RESULTS:
      During the first 4 weeks, body-fat percentage decreased in the SIV-infected
      macaques while lean-tissue percentage increased; during weeks 4-72, these
      macaques lost a greater percentage of total fat tissue but had more subcutaneous
      fat deposition than did the uninfected control macaques. Just prior to death, the
      SIV-infected macaques that died (n=7) had a greater loss in body-mass index,
      abdominal fat, fat tissue, and lean tissue, compared with that in SIV-infected
      macaques that survived (n=5). CONCLUSIONS: Body-composition changes in SIV
      infected juvenile macaques exhibit 3 phases: during acute infection, loss of body
      weight from fat tissue; a compensation period during which macaques grow, but at
      a reduced rate; and a terminal phase, during which tissue is lost from all body
      compartments. The SIV-infected juvenile macaque provides a useful model for the
      investigation of wasting in AIDS, particularly for pediatric AIDS wasting.

PMID- 15143466
TI  - Release of anti-HIV mediators after administration of leukotriene B4 to humans.
AB  - BACKGROUND: CD8(+) T cells can control human immunodeficiency virus (HIV) through
      the lysis of infected cells and the release of soluble mediators, such as
      macrophage inflammatory protein (MIP)-1 beta, which prevent entry of HIV and/or
      inhibit HIV replication. Because neutrophils represent a major source of alpha
      defensins and, to a lesser extent, MIP-1 beta, we determined whether leukotriene
      B(4) (LTB(4)), a potent neutrophil agonist, would trigger the release of these 2
      anti-HIV peptides. METHODS: Plasma samples from HIV-uninfected subjects receiving
      intravenous bolus of LTB(4) were analyzed for alpha-defensins and MIP-1 beta
      levels by use of enzyme-linked immunosorbent assay. Furthermore, in vitro
      analysis of intracellular and secreted levels of alpha-defensins of resting and
      LTB(4)-activated neutrophils from HIV-uninfected and HIV-infected subjects were
      determined. LTB(4) modulation of CD63 and CD66b markers associated with
      degranulation were studied by use of flow cytometry. Chemotaxis of neutrophils
      from HIV-uninfected and HIV-infected subjects toward LTB(4) or interleukin (IL)-8
      was determined by use of migration assays. RESULTS: Administration of LTB(4) to
      humans caused a dose-dependent plasmatic increase in alpha-defensins and MIP-1
      beta proteins, with peak levels observed 2 h after administration of LTB(4).
      Neutrophils isolated from HIV-infected and HIV-uninfected subjects contained
      similar levels of stored alpha-defensins that were effectively secreted in vitro,
      in response to LTB(4) activation. Chemotaxis of neutrophils toward LTB(4) or IL-8
      was identical among the groups of subjects. CONCLUSION: LTB(4) induced the
      secretion alpha-defensins and MIP-1 beta. Neutrophils from HIV-infected subjects
      were fully responsive to LTB(4), which highlights a potential usefulness of this
      lipid mediator in the management of HIV infection.

PMID- 15143468
TI  - Reduced levels of neutralizing antibodies to Kaposi sarcoma-associated
      herpesvirus in persons with a history of Kaposi sarcoma.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) has been identified as the etiologic
      agent of Kaposi sarcoma (KS). Although KSHV is required for the development of
      KS, immune dysfunction is a common and important cofactor in the development of
      KS, as illustrated by the presence of KS in association with HIV infection or
      immunosuppressive-drug treatment after transplantation. Because neutralizing
      antibodies (NAb) constitute an important component of an antiviral immune
      response, we examined the functionality of the humoral immune response associated
      with KS, by measuring KSHV NAb titers in 3 groups of subjects. Group 1 included
      subjects who were KSHV positive, KS positive, and human immunodeficiency virus
      (HIV) positive; group 2 included subjects who were KSHV positive, KS negative,
      and HIV positive; and group 3 included subjects who were KSHV positive, KS
      negative, and HIV negative. NAb titers were significantly lower among subjects
      with KS, compared with subjects who were infected with KSHV but who did not have
      clinical evidence of KS, in a multivariate model adjusted for HIV infection and
      CD4 T cell count. The data from the present study suggest that NAb may play a
      role in the control of KSHV infection and the prevention of progression of KSHV
      infection to KS.

PMID- 15143469
TI  - Familial clustering of classic Kaposi sarcoma.
AB  - It is widely accepted that there is a causal association between Kaposi sarcoma
      associated herpesvirus (KSHV) and Kaposi sarcoma (KS). However, the majority of
      individuals infected with KSHV never develop KS. Here, we present a unique
      familial case of classic KS, in which the disease occurs in 4 siblings who have
      no recognized underlying immunodeficiency. We examine risk factors that could
      play a role in this condition, including KSHV infection, KSHV DNA load, genetic
      variants of KSHV, infection with additional viruses, interleukin-6-promoter
      polymorphism, and HLA genotype. We hypothesize that a genetic susceptibility to
      KS, in combination with KSHV infection, may play an important role in the
      presented familial case.

PMID- 15143470
TI  - Seroepidemiology and risk factors for sporadic norovirus/Mexico strain.
AB  - Risk factors associated with transmission of sporadic norovirus (NV; formerly
      Norwalk-like virus)/Mexico strain were identified in a seroepidemiological study
      conducted in rural Mexico. Acquisition of Mexico strain IgA antibodies was age
      related; 34% of 1-4-year-olds were seropositive, compared with 81% of adults
      (P<.001). After 12 months, 42% of 1-4-year-olds showed a seroresponse to Mexico
      strain, compared with 27% of adults (P<.01). Personal and domestic hygiene
      measures, such as hand washing, general cleanliness of the mother's clothing, and
      the type of room assigned for cooking were significantly associated with odds of
      a seroresponse. For infants, having a dog in or near the home was a risk factor
      for seroresponse (P<.01), whereas, for older children, the mother's involvement
      in agricultural activities was a risk factor (P<.001). This study provides
      initial evidence of risk factors associated with sporadic NV infection. Data
      indicate some similarities to risk factors associated with outbreaks of NV
      infection.

PMID- 15143471
TI  - Hepatitis C virus quasi-species dynamics predict progression of fibrosis after
      liver transplantation.
AB  - BACKGROUND: The dynamics of hepatitis C virus (HCV) quasi species in the E2
      region may correlate with the course of infection after orthotopic liver
      transplantation (OLT). METHODS: Thirty-four patients who underwent
      transplantation for HCV-related cirrhosis were studied. Serum and liver samples
      were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients
      were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year, <2) and
      group 2 (FS at 1 year, > or =2). Complexity was estimated by the number of bands
      in a single-strand conformational polymorphism assay, whereas diversity was
      measured by Shannon entropy (SE) and median mobility shift (MMS) values derived
      from the heteroduplex mobility assay. Diversity dynamics were measured at
      transmission (before OLT vs. 1 week after OLT) and after OLT (1 week after OLT
      vs. 1 year after OLT). RESULTS: Complexity was higher in group 1 patients than in
      group 2 patients before OLT (P<.02) and at 1 week after OLT (P<.04). Diversity
      decreased in group 1 at transmission, as measured by either SE (P<.01) or MMS
      (P<.04). However, diversity increased in this group after OLT, as measured by SE
      (P<.03) or MMS (P<.02). FS at 1 year after OLT correlated with transmission
      changes, as measured by SE (r=0.642, P<.0001) and MMS (r=0.443, P<.04), and with
      post-OLT changes (for SE: r=-0.583, P<.01; for MMS: r=-0.536, P<.01).
      CONCLUSIONS: HCV complexity and diversity in the E2 region correlated with the
      severity of recurrence of HCV infection after OLT. Increased diversity of quasi
      species at transmission correlated with a higher FS at 1 year. However, increased
      diversity of quasi species in the post-OLT period correlated with a lower FS at 1
      year. The dynamics of HCV quasi species in patients who undergo transplantation
      are predictive of outcome.

PMID- 15143472
TI  - Differential production of inflammatory cytokines in primary infection with human
      metapneumovirus and with other common respiratory viruses of infancy.
AB  - Viral respiratory infections are the most frequent cause of hospital admission
      for infants and young children during winter. However, the mechanisms of illness
      that are associated with viral lower-respiratory-tract infection (LRI) are
      unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in
      infants to the induction of innate inflammatory responses. This theory is
      supported by studies showing that Toll-like receptor 4 is activated by
      respiratory syncytial virus (RSV), leading to production of inflammatory
      cytokines. We prospectively examined previously naive infants in Buenos Aires,
      Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection
      with human metapneumovirus (hMPV) was second only to RSV in frequency. Both
      viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV
      elicited significantly lower levels of respiratory inflammatory cytokines than
      did RSV. Symptoms in infants infected with influenza virus were different from
      those in infants infected with RSV, but cytokine responses were similar. These
      findings suggest that hMPV and RSV either cause disease via different mechanisms
      or share a common mechanism that is distinct from innate immune activation.

PMID- 15143473
TI  - Association between common Toll-like receptor 4 mutations and severe respiratory
      syncytial virus disease.
AB  - BACKGROUND: The clinical spectrum of respiratory syncytial virus (RSV)
      bronchiolitis in previously healthy infants is extremely variable. Thus, it is
      likely that factors such as genetic heterogeneity contribute to disease severity.
      Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in
      the innate immune response to RSV. METHODS: The association of the TLR4 mutations
      (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99
      infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two
      ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults
      (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159
      polymorphism were genotyped by use of reverse-transcriptase polymerase chain
      reaction and restriction fragment-length polymorphism analysis, respectively.
      RESULTS: Each of the TLR4 mutations, either alone or in cosegregation, were
      associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations
      were significantly overrepresented in group I, compared with groups II and III.
      No association between the CD14/-159 polymorphism and RSV bronchiolitis was
      found. CONCLUSIONS: These findings suggest that TLR4 mutations, but not the CD14/
      159 polymorphism, are associated with an increased risk of severe RSV
      bronchiolitis in previously healthy infants.

PMID- 15143474
TI  - Protection against challenge with measles virus (MV) in infant macaques by an MV
      DNA vaccine administered in the presence of neutralizing antibody.
AB  - Measles virus (MV) infection is the major cause of vaccine-preventable death in
      infants and children worldwide. It is difficult to achieve immunity to MV
      infection by use of vaccines in infants during the first 6-9 months of life
      because of the presence of maternal antibody. Morbidity and mortality due to MV
      infection would decrease substantially if a vaccine administered at birth could
      prime immunity in the presence of maternal antibody. We demonstrate here that an
      MV DNA vaccine administered to infant macaques in the presence of maternal
      antibody primes MV-specific T cell responses but not de novo neutralizing
      antibody. This vaccine protected 80% of the infant macaques from skin rash and MV
      induced immunosuppression. A molecular interleukin-2 adjuvant was required for
      protection with this vaccine. This macaque model shows that infants can be
      vaccinated against MV in the presence of maternal antibody. These results suggest
      that it is possible to develop an MV DNA vaccine that could protect infants in
      developing countries during the first months of life.

PMID- 15143475
TI  - The hamster as an animal model for eastern equine encephalitis--and its use in
      studies of virus entrance into the brain.
AB  - Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral
      diseases in the United States, with mortality rates of 30%-70%. Vasculitis
      associated with microhemorrhages in the brain dominates the pathological picture
      in fatal human eastern equine encephalitis, and neuronal cell death is detectable
      during the late stage of the disease. We describe use of the golden hamster to
      study EEEV-induced acute vasculitis and encephalitis. In hamsters, EEEV
      replicates in visceral organs, produces viremia, and penetrates the brain. The
      pathological manifestations and antigen distribution in the brain of a hamster
      are similar to those described in human cases of EEEV.

PMID- 15143476
TI  - Similar antibody concentrations in Filipino infants at age 9 months, after 1 or 3
      doses of an adjuvanted, 11-valent pneumococcal diphtheria/tetanus-conjugated
      vaccine: a randomized controlled trial.
AB  - In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate
      vaccine (serotypes 1, 4, 5, 7F, 9V, 19F, and 23F conjugated to tetanus protein;
      and serotypes 3, 6B, 14, and 18C conjugated to diphtheria toxoid) administered
      alone at age 18 weeks (11PncTD1) elicited similar antibody concentrations at age
      9 months as those elicited by 3 doses (11PncTD3) administered concomitantly with
      national program vaccines, at ages 6, 10, and 14 weeks. Geometric mean antibody
      concentrations ranged from 0.36 microg/mL (for serotype 18C) to 5.81 microg/mL
      (for serotype 4), for the 11PncTD1 vaccine, and from 0.32 microg/mL (for serotype
      18C) to 5.01 microg/mL (for serotype 19F), for the 11PncTD3 vaccine. The
      proportion of infants with threshold antibody concentrations > or =0.35 microg/mL
      was also similar (ranges, 55.6%-100% for the 11PncTD1 vaccine and 42.9%-100% for
      the 11PncTD3 vaccine). The functional activity of antibodies expressed as
      opsonophagocytic activity titers was similar in the 11PncTD1 and 11PncTD3 groups.
      This finding is an important one for countries with financial constraints and
      high pneumococcal disease burden.

PMID- 15143478
TI  - A molecular marker for evaluating the pathogenic potential of foodborne Listeria
      monocytogenes.
AB  - BACKGROUND: Internalin mediates entry of Listeria monocytogenes into some human
      cultured cell lines and crossing of the intestinal barrier in transgenic mice
      expressing its receptor, human E-cadherin, in enterocytes. The relevance of these
      findings for humans is challenged by the observation that some L. monocytogenes
      isolates express a truncated nonfunctional form of internalin. METHODS: We
      investigated expression of internalin by use of immunoblot assay in 300 clinical
      strains obtained in France in a single year and a representative set of 150
      strains obtained from food products during the same period. RESULTS: Clinical
      strains expressed full-length internalin far more frequently (288/300 strains
      [96%]) than did strains recovered from food products (98/150 strains [65%]; odds
      ratio, 12.73; 95% confidence interval, 6.27-26.34; P<1 x 10(-7)). All 61 strains
      (100%) from pregnancy-related cases, 55 (98%) of 56 strains from patients with
      central nervous system infections, and 151 (93%) of 162 strains from patients
      with bacteremia expressed full-length internalin. All 110 strains belonging to
      serovar 4b, the most frequently implicated serovar in human listeriosis,
      expressed full-length internalin. CONCLUSIONS: This study demonstrates the
      critical role of internalin in the pathogenesis of human listeriosis. It provides
      a molecular explanation for the predominance of serovar 4b among clinical strains
      and supports the usefulness of studying the expression of internalin as a marker
      of virulence in humans.

PMID- 15143479
TI  - Impairment of growth of Listeria monocytogenes in THP-1 macrophages by
      granulocyte macrophage colony-stimulating factor: release of tumor necrosis
      factor-alpha and nitric oxide.
AB  - BACKGROUND: Listeria monocytogenes tends to survive in phagocytes. Granulocyte
      macrophage colony-stimulating factor (GM-CSF) protects mice against L.
      monocytogenes infection, and mice knocked out for the GM-CSF gene are more
      susceptible to these infections. METHODS: THP-1 cells were used to characterize
      the GM-CSF receptor (binding isotherms; STAT5 phosphorylation), measure the
      intracellular growth of L. monocytogenes (5 h after phagocytosis), examine the
      influence of a 24-h incubation with GM-CSF before infection, measure the
      production of tumor necrosis factor (TNF)-alpha and the expression of nitric
      oxide synthase (iNOS), and evaluate the influence of anti-GM-CSF receptor (GM
      CSFR alpha ) and anti-TNF-alpha antibodies and the addition of N(omega)-nitro-L
      arginine methyl ester (L-NAME) and catalase. RESULTS: THP-1 cells display
      functional GM-CSFR alpha. GM-CSF impairs the intracellular growth of L.
      monocytogenes to approximately 65% of its value in unstimulated cells. This
      effect is abolished by anti-GM-CSFR alpha, anti-TNF-alpha antibodies, and
      catalase (and, to a lesser extent, by L-NAME). GM-CSF stimulates the release of
      TNF-alpha and the expression of iNOS. TNF-alpha added to unstimulated cells (even
      in large amounts) does not fully reproduce the impairment in the growth of L.
      monocytogenes caused by GM-CSF. CONCLUSIONS: GM-CSF impairs the intracellular
      growth of L. monocytogenes by a synergistic action of the GM-CSF-triggered
      release of autocrine TNF-alpha and hydrogen peroxide and the production of NO
      (associated with the stimulation of the expression of iNOS).

PMID- 15143477
TI  - Quinolone resistance-determining region mutations and por type of Neisseria
      gonorrhoeae isolates: resistance surveillance and typing by molecular
      methodologies.
AB  - Quinolone resistance is increasing rapidly in Neisseria gonorrhoeae and is a
      significant public health problem that requires ongoing surveillance. To examine
      the feasibility of molecular surveillance of quinolone resistance, and to further
      characterize an outbreak of resistant N. gonorrhoeae in Israel, the quinolone
      resistance-determining region (QRDR) sequences and the por types of 80 N.
      gonorrhoeae isolates were determined using molecular techniques. QRDRs of gyrA
      and parC were amplified by polymerase chain reaction and were sequenced directly.
      The por type was determined by checkerboard hybridizations performed using
      oligonucleotide probes to regions encoding 5 variable loops of the porin protein.
      All 42 ciprofloxacin-resistant (CipR) isolates had mutations in QRDRs of both
      gyrA and parC, and identical mutations were found in 93% of these isolates. One
      intermediately resistant isolate had 1 mutation in gyrA, and susceptible isolates
      showed no mutations. Forty isolates had 1 of 2 por types that differed only by an
      in-frame deletion in variable region 5; all but 1 of these isolates were CipR.
      QRDR sequencing and por type determination showed that the outbreak of CipR N.
      gonorrhoeae in Israel was clonal. QRDR mutations were consistent with those
      previously characterized; this indicates that DNA probes can be developed for
      rapid detection and surveillance of quinolone-resistant N. gonorrhoeae in
      settings in which nonculture diagnostic methods are used.

PMID- 15143480
TI  - Differential effects of varying concentrations of clostridium difficile toxin A
      on epithelial barrier function and expression of cytokines.
AB  - BACKGROUND: Presentation after Clostridium difficile infection may depend on the
      level of epithelial exposure to toxins. We investigated epithelial barrier
      function and expression of interleukin (IL)-8 and transforming growth factor
      (TGF)-beta in response to varying concentrations of C. difficile toxin A.
      METHODS: T84 cells were either preexposed or continuously exposed to C. difficile
      toxin A (0.01-1000 ng/mL). Barrier function was assessed by measurements of
      transepithelial electrical resistance. RESULTS: Preexposure to < or =10 ng/mL
      toxin A led to an increase in the release of TGF-beta 1, but there was no change
      in the expression of IL-8. In contrast, after preexposure to >10 ng/mL toxin A,
      there was enhanced expression of IL-8, but release of TGF-beta 1 was similar to
      that in control monolayers. After preexposure to >10 ng/mL toxin A, there was
      complete and irreversible loss of electrical resistance. At lower concentrations,
      loss of resistance across monolayers was followed by recovery, which was enhanced
      by all 3 recombinant isoforms of TGF-beta. Pretreatment with recombinant isoforms
      of TGF-beta or coculture with TGF-beta 3-expressing colonic subepithelial
      myofibroblasts was also protective. CONCLUSIONS: In C. difficile infection, the
      development and severity of colonic inflammation may depend on the exposure of
      intestinal epithelial cells to toxins and the expression of proinflammatory (IL
      8) and protective (TGF-beta) factors.

PMID- 15143482
TI  - Sphingosine 1-phosphate induces antimicrobial activity both in vitro and in vivo.
AB  - Sphingosine 1-phosphate (S1P), a polar sphingolipid metabolite, is involved in a
      wide spectrum of biological processes, including Ca(++) mobilization, cell
      growth, differentiation, motility, and cytoskeleton organization. Here, we show a
      novel role of S1P in the induction of antimicrobial activity in human macrophages
      that leads to the intracellular killing of nonpathogenic Mycobacterium smegmatis
      and pathogenic M. tuberculosis. Such activity is mediated by host phospholipase
      D, which favors the acidification of mycobacteria-containing phagosomes.
      Moreover, when it was intravenously injected in mycobacteria-infected mice, S1P
      reduced mycobacterial growth and pulmonary tissue damage. These results identify
      S1P as a novel regulator of the host antimicrobial effector pathways.

PMID- 15143483
TI  - Transmission of acute infectious nonbacterial gastroenteritis to volunteers by
      oral administration of stool filtrates. 1971.

PMID- 15143481
TI  - Differential induction of apoptosis and necrosis in monocytes from patients with
      tuberculosis and healthy control subjects.
AB  - BACKGROUND: Mycobacterium tuberculosis and purified protein derivative (PPD)
      induce apoptosis in murine macrophages and apoptosis and necrosis in human
      monocytes and alveolar epithelial cells. Macrophages from bronchoalveolar lavages
      and granulomas from patients with tuberculosis (TB) present both types of cell
      death; however, the significance of the type of cell death in TB remains
      uncertain. METHODS: Monocytes from PPD-positive control subjects and from
      patients with TB were exposed to PPD or M. tuberculosis. Apoptosis, necrosis, and
      the percentage of tumor necrosis factor (TNF)-alpha -positive and interleukin
      (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate
      dehydrogenase, TNF-alpha, and IL-10 were measured in culture supernatants. The
      role of TNF-alpha and IL-10 was tested by blockade experiments. RESULTS: PPD and
      M. tuberculosis induced apoptosis in monocytes from PPD-positive control
      subjects, whereas cells from patients with TB presented apoptosis and necrosis.
      Cells from PPD-positive control subjects produced mainly TNF-alpha, whereas cells
      from patients with TB produced mainly IL-10. Blockade experiments suggest that
      TNF-alpha and IL-10 regulate the type of cell death occurring in response to M.
      tuberculosis. CONCLUSIONS: Results suggest that apoptosis of monocytes exposed to
      mycobacteria may partly explain the protective immune response found in PPD
      positive control subjects, whereas necrosis may be determinant of the bacterial
      dissemination and tissue damage that occur in patients with active TB.

PMID- 15143484
TI  - Dental plaque revisited: bacteria associated with periodontal disease.
AB  - Between 3-12 weeks after the beginning of supragingival plaque formation, a
      distinctive subgingival microflora predominantly made up of gram-negative,
      anaerobic bacteria and including some motile species, becomes established. In
      order to establish in a periodontal site, a species must be able to attach to one
      of several surfaces including the tooth (or host derived substances adhering to
      the tooth), the sulcular or pocket epithelium, or other bacterial species that
      are attached to these surfaces (Socransky and Haffajee 1991). Bacterial adhesion
      has demonstrated specificity in the mechanisms involved and studies have shown
      that there is a diversity of receptors on tooth surfaces, epithelial or other
      host cells and other bacteria. Recent studies have described bacterial complexes
      that are present in subgingival plaque and these studies are likely to help in
      current understanding of the complex ecology observed in dental plaque biofilm
      (Socransky, Haffajee et al. 1998). Bacterial interactions play important roles in
      species survival. Some interspecies relationships are favourable, in that one
      species produces growth factors for, or facilitates attachment of, another
      species. Other relationships are antagonistic due to competition for nutrients
      and binding sites, or to the production of substances that limit or prevent the
      growth of another species (Socransky and Haffajee 1991). A number of different
      bacterial interactions within plaque biofilm have been discussed. In the last 30
      40 years, a vast amount of evidence has been published to suggest that bacteria
      are the primary aetiological agents of periodontal diseases. In the 1950s and
      early 1960s, periodontal treatment was based on the non-specific plaque
      hypothesis. However, the non-specific plaque hypothesis gave way after studies
      suggested that not all organisms in plaque are equally capable of causing
      destructive periodontal disease. Thus the concept of specificity re-emerged.
      Criteria for defining periodontal pathogens have been developed and include
      association, elimination, host response, virulence factors, animal studies and
      risk assessment (Haffajee and Socransky 1994). Until recently there were few
      consensus periodontal pathogens and trying to discriminate pathogenic from non
      pathogenic species has been a difficult task for dental researchers for a variety
      of reasons. A discussion of the specific microbiota associated with gingivitis,
      chronic and aggressive periodontitis, NUG, HIV-associated periodontitis and
      implantitis has been presented. The bacteria associated with periodontal diseases
      are predominantly gram-negative anaerobic bacteria and may include A.
      actinomycetemcomitans, P. gingivalis, P. intermedia, B. forsythus, C. rectus, E.
      nodatum, P. micros, S. intermedius and Treponema sp. The bacterial numbers
      associated with disease are up to 10(5) times larger than those associated with
      health.

PMID- 15143485
TI  - An investigation into the bristle action of electric toothbrushes.

PMID- 15143486
TI  - Spontaneous closure of diastema following periodontal therapy.

PMID- 15143487
TI  - [Response of the spinal trigeminal nucleus neurons to electric stimulation of the
      rat dura mater].
AB  - Aseptic inflammation of tissues surrounding large meningeal blood vessels, e.g.
      the superior sagittal sinus, underlies pathogenesis of migraine. This
      inflammation develops due to antidromic activation of sensory trigeminal nerve
      endings and is followed by changes in responses of the spinal nucleus of the
      trigeminal nerve neurons to electrical stimulation of the superior sagittal
      sinus. However, characteristics of these reactions are still unclear. In
      experiments ou urethane-anesthetized rats, responses of 387 neurons of the spinal
      nucleus of the trigeminal nerve to electrical stimulation of the superior
      sagittal sinus, were recorded. It was tial discharge with the latency 7 to 19 ms
      (11.4 +/- 0.17 ms) and a subsequent long-lasting discharge with the latency 20 to
      50 ms (34.2 +/- 0.8 ms). It is presumed that the first phase reflects orthodromic
      activation of prevascular A delta and C-fibers of the trigeminal nerve while the
      second phase is connected with activation of meningeal C-fibers which have low
      conduction velocity, and/or with a secondary activation of perivascular sensory
      endings of trigeminal nerve by releasing algogenic and vasoactive substances.
      These changes could be used as an indicator of efficacy of some antimigraine
      substances in animal experiments.

PMID- 15143488
TI  - [Change in serotonin metabolism in the rat brain in response to the repeated
      stimulus presentation].
AB  - The content of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5
      HIAA), monoamine oxidase (MAO) activity and kinetic parameters (K(m) and Vmax)
      for the reaction of 5-HT deamination, were examined in various regions of the rat
      brain after repeated presentation of a contextual stimulus. Habituation to the
      stimulus was accompanied by an increase of 5-HT metabolism and active transport
      of 5-HIAA in the amygdala, striatum and midbrain, while these changes were not
      found in the prefrontal cortex and hippocampus. Kinetic studies have revealed
      that the enhancement of 5-HT deamination by MAO in the brain structures was
      mediated by different catalytic mechanisms. A significant decrease in K(m) value
      for 5-HT deamination in the amygdala indicated an increase in the affinity of
      enzyme towards 5-HT. In the striatum the enhanced MAO activity was provided by
      increasing maximal rate of 5-HT deamination. It is concluded that an activation
      of presynaptic mechanisms of the serotonergic transmission in the amygdala and
      striatum is involved in the inhibition of biological significance and attention
      to repeated presentation of stimulus.

PMID- 15143489
TI  - [Characteristics of the human cardiovascular system in the human diving
      response].
AB  - Comparative-evolutional research of diving response showed that mechanisms of its
      expression had much in common in humans and in animals. Firstly, it involves a
      reflex bradycardia, vasoconstriction of peripheral vessels, and blood flow
      centralization. But, unlike animals whose diving response has some typical
      species peculiarities, human diving response is rather diverse. Four types of
      cardiovascular system response to face submersion were revealed: over-reactive,
      reactive, paradoxical, and nonreactive. These types were chosen according to the
      bradycardia character. It is also supposed that the occurrence of individual
      maximal R--R-interval, while serving as a signal to apnea stopping, is among the
      reasons of apnea activity limitation.

PMID- 15143490
TI  - [Role of adrenoreceptors in the effect of thyroliberin on lymphatic vessels].
AB  - Formerly we showed that TRH had simulative effect on mesenteric bovine and rat
      lymphatic vessels (LV) in very low concentration--10(-12)-10(-18) M. In present
      paper, participation of LV alpha- and beta-receptors in realization of TRH
      activity on rat mesenteric lymphatic vessels was studied in situ. Propranolol
      increased the stimulative effect of TRH, isoproterenol exerted an opposite
      effect. Phentolamine, prazosin eliminated the simulative effect of TRH, yohimbine
      resulted in additional gain of effect, which seems to testify 1) presynaptic
      action of TRH or 2) increase of the output of norepinephrine, which is
      potentiated by alpha 2-adrenoceptor antagonists. Also the participation of
      adrenergic receptors in positive chronotropic effects of mesenteric rat LV was
      studied using the method of selective destruction of dopamine-containing neurons
      after 6-OHDA infusion. As it occurred, desympathization hindered development of
      stimulating action of TRH. Thus, the efficiency of TRH as a stimulator of LV is
      connected with activation of adrenergic mechanisms.

PMID- 15143492
TI  - [Effect of erythrocytes from intact, polycythemic, and anemic rats on
      erythropoiesis in erythroblastic island culture].
AB  - Comparison of influence of erythrocytes of different stages of maturity, and
      their amount on erythropoiesis in erythroblastic island culture revealed their
      dose-dependent and maturity-dependent inhibiting effect on erythropoiesis.
      Erythrocytes of polycythemic rats inhibit maturing and formation of
      erythroblastic islands more intensively than erythrocytes of normal on anemic
      rats.

PMID- 15143491
TI  - [Ischemic adaptation of the rat brain as a method for protection of endothelium
      from ischemic reperfusion injury].
AB  - This study represents results of investigation carried out to determine the
      endothelium-protective effect of early and late phases of brain ischemic
      preconditioning as well as local and remote adaptation. The experiments were
      performed on adult male rats. Prolonged 30-min four vessels brain ischemia
      followed by 120-min reperfusion on carotid arteries, was performed (control
      group). Early and late local ischemic preconditioning was due to both 5-min
      ischemia and 30-min and 48 h reperfusion respectively on carotid arteries. Remote
      ischemic preconditioning was caused by 30-min ischemia and also by 15-min and 48
      h reperfusion, respectively (early and late phases of adaptation) on femoral
      artery before prolonged brain ischemia described above. To estimate the role of
      nitric oxide in ischemic adaptation, mechanisms involved both nonselective
      blocker of NO-synthesis (N omega-nitro-L-arginine) in the time of early
      adaptation phase and the relatively selective iNOS inhibitor S-methylisothiourea
      sulfate, given before sustained brain ischemia, on the late preconditioning.
      Registration of brain blood flow was made by ultrasonic high-frequency Doppler
      device. Degree of brain edema was studied and evaluation of desquamated
      endothelial cells in blood was carried out. Early and late phases of local
      ischemic preconditioning were found to improve the brain blood flow and level of
      circulatory endothelial cells as well as to reduce degree of edema. The
      endothelium-protective effect of remote ischemic preconditioning has been proved
      in this study only on the late phase. Nitric oxygen was found to be important
      endothelium-protective factor in ischemic preconditioning.

PMID- 15143495
TI  - [The acoustic aspect of the speech development in children during the third year
      of life].
AB  - The current part of a Russian language acquisition longitudinal study based on
      auditory, phonetic and instrumental analysis is devoted to the third year of
      child's life. We examined the development of supplementary acoustic and phonetic
      features of the child's speech providing for the possibility for the speech to be
      recognized. The instrumental analysis and statistical processing of vowel formant
      dynamics as well as stress, palatalization and VOT development, has been
      performed for the first time in Russian children. We showed that the high
      probability of children words recognition by auditors was due to establishment of
      a system of acoustically stable features which, in combination with each other,
      provide for the informative sufficiency of a message.

PMID- 15143494
TI  - [Free radical mechanism of the cold stress development in rats].
AB  - Development of cold stress in rats is characterized by sharp activation of lipid
      peroxidation accompanied by a considerable increase of the diene conjugates level
      and Schiff bases in tissues of brain, liver and in erythrocytes. There is a shift
      in the prooxidant--antioxidant balance of the organism in the form of
      amplification of xanthine oxidase prooxidant enzymatic activity in the brain and
      liver, and a decrease of myeloperoxidase activity in blood neutrophiles of rats.
      The attrition at cold stress, mainly, of enzymatic endocellular antioxidant
      system as the result of inhibition of superoxide dismutase, catalase, glutathione
      reductase activities in brain, liver and erythrocytes is indemnified by
      activation of non-enzymatic antioxidant mechanisms. In conditions of cold stress,
      destabilization of erythrocyte membranes of rats described by a decrease of the
      microviscosity of protein-lipid contact zones and reduction of degree of
      immersing of proteins in lipid membrane owing to exhibiting proteins from the
      hydrophobic zone of membranes, or their aggregate, increase of polarity of lipid
      phase and negative surface charge, is marked.

PMID- 15143493
TI  - [Functional interaction between nicotinic cholinergic receptors and Na, K-ATPase
      in the skeletal muscles].
AB  - Acetylcholine (ACh) hyperpolarized the rat diaphragm muscle fibers by 4.5 +/- 0.8
      mV (K0.5 = = 36 +/- 6 nmol/l). The AC-induced hyperpolarization was blocked by d
      tubocurarine and ouabain in nanomolar concentrations. This effect of ACh was not
      observed in cultured C2C12 muscle cells and in Xenopus oocytes with expressed
      embryonic mouse muscle nicotinic acetylcholine receptors (nAChR) or with neuronal
      alpha 4 beta 2 nAChR. In membrane preparations from the Torpedo californica
      electric organ, containing both nAChR and Na, K-ATPase, 10 nmol/l ouabain
      modulated the binding kinetics of the cholinergic ligand dansyl-C6-choline to the
      nAChR. These results suggest that in-sensitive alpha 2 isoform) and nAChR in a
      state with high affinity to Ach and d-tubocurarine may form a functional complex
      in which binding of ACh to nAchR is coupled to activation of the Na, K-ATPase.

PMID- 15143496
TI  - [Effect of age on absorption and membrane digestion in the rat small intestine].
AB  - By the short-circuit current method in our modification, kinetic constants for
      nutrient transporters in rat gastric-intestinal tract and unstirred layer
      thickness near mucosa surface, were studied. In experiments on rats it was shown
      that in ageing, the nutrient monomer transporters number in the small intestine
      increases twofold, while its affinity to correspondent nutrients remains
      unchanged. For the peptide the situation may be the opposite one. The layer
      thickness in the vicinity of mucosa surface measured by glucose decreased in
      ageing. It was suggested that in old rats the role of volume digestion is
      enhanced resulting in adapting increase of nutrient monomer transporters number.

PMID- 15143497
TI  - [Differential evacuation activity of the human gastroduodenal complex].
AB  - In clinical healthy volunteers (20) the rapid of gastric evacuation of three
      types of test meals: the gruel with egg protein or butter are investigated by
      sonography. There are investigated (117): the half-time of evacuation, the area
      of a diameter of the antrum in the systole and diastole, the amplitude of the
      contraction and the frequency of it. In healthy volunteers the differentiative
      evacuation of the three types of the test meals are established. The reception of
      pancreatin (KREON 10,000) with the test meals are increasing the speed of it
      evacuation, but without changing the differentiative of gastric evacuation.

PMID- 15143498
TI  - [Gastric secretion in dogs following three day fasting and resumed feeding].
AB  - The investigation into the influence of a three-day starvation on the gastric
      secretion in dogs with Pavlov pouches stimulated by meat, histamine and
      pentagastrin, was carried out. A 72-hour starvation did not change the summary
      volume of the gastric juice, debit of the gastric acid, and quantity of pepsin.
      At the same time the starvation decreased the average rate of gastric juice
      secretion, gastric acid and pepsin secretion in response to histamine and
      decreased the pepsin secretion in response to pentagastrin. In this way re
      feeding enhanced the average rate of gastric juice secretion and gastric acid
      secretion on 3-day and pepsin on 5-day in response to meat. The average rate of
      gastric juice secretion increased on the 5-day after refeeding in response to
      histamine and the average rate of gastric juice, gastric acid and pepsin
      secretion in response to pentagastrin.

PMID- 15143500
TI  - [Effect of microinjections of a selective blocker of M1-muscarinic receptors
      pirenzepine into the neostriatum on the rat motor activity].
AB  - In simulated discrimination conditioned reflex of active avoidance (CRAA) in T
      maze, the effect of bilateral microinjections of the muscarinic receptor M1
      selective blocker pirenzepine on the CRAA formation and behaviour in the "open
      filed" test, was studied in rats. A sharp worsening of the CRAA learning and a
      significant increase in the motor activity were shown to occur in rats following
      the microinjections as compared with control rats. The change in the motor
      responses seems to account for the worsening of the CRAA learning. Another reason
      of the phenomenon could involve a disorder in perception of conditioned signals
      and their poor differentiation. The data obtained and the literature data suggest
      a complex character of changes induced by the blockade of the M1 muscarinic
      receptors of the neostriatum.

PMID- 15143499
TI  - [Hyperexcitability CA1 neurons induced by brief episodes of hypoxia in
      hippocampal slices in rats of various age groups].

PMID- 15143502
TI  - [Interhemispheric asymmetry of the hippocampal damage after bilateral ligation of
      common carotid arteries].
AB  - Permanent bilateral occlusion of common carotid arteries in rats with different
      behaviour types led to non-uniform structural alterations in the hippocampus. In
      the majority of animals, morphological changes were diffuse (i.e. having no clear
      localisation in a definite region of the brain structure) and symmetrical (i.e.
      having no evident prevalence in one of the brain hemispheres). In 6.6% of
      survived animals, apart from diffuse structural changes, local and asymmetrical
      sites of lesions occurred in the hippocampus and mostly in the dorso-lateral
      thalamic nuclei of the right brain hemisphere. These local zones of strongly
      pronounced pathology corresponded to ischemic insults which were described
      earlier by other authors under transient cerebral ischemia. It is supposed that
      the occurrence of unilateral ischemic insults in a definite region of hippocampus
      and thalamus after bilateral occlusion of common carotid arteries is due to
      individual features of the anatomy of the vascular brain system which are found
      more frequently in rats with passive type of behaviour and in rats of the middle
      group than in rats with active type of behaviour.

PMID- 15143501
TI  - [The central nucleus of the amygdala: cytoarchitechtonics, neuronal organization,
      and histophysiology].
AB  - Neurologists' attention is attracted by amygdala's central nucleus which takes
      part in formation of stress response and adaptive behaviour in animals. The data
      on cytoarchitectonics, neuronal organization and histophysiology of this
      important centre are based on current knowledge of its subnuclear organization.

PMID- 15143503
TI  - [Vital investigation of the genome activity and neuronal synaptic plasticity in
      snail in the course of learning].
AB  - Vital investigation of genome activity and its role in mechanisms of long-term
      synaptic plasticity formation were studied in LP11 neuron (command neurone of
      defence behaviour) during sensitisation (simple form of learning) in semi-intact
      preparation of snail Helix lucorum. Genome activity was investigate by means of
      specific fluorescent dye SYTO 16 and image analysis system. It was found that
      application of sensitizing stimulation (10% quinine solution) onto the snail head
      initiate two-phase changes in neural responses evoked by tactile or chemical
      stimulation. Depression of neural responses was obtained during short-term phase
      (during 1 hour after sensitization) and facilitation of neural responses--during
      long-term phases (over 1 hour). At the same time (15-20 min after learning), a
      significant increase in SYTO 16 fluorescent level was found in nucleus site LP11
      neurone. Initial SYTO 16 fluorescence level was registered in 4-5 hours after
      sensitization. If the sensitization was produced during actinomycin D application
      (inhibitor of RNA synthesis, 20 microM) then facilitation of neural responses
      evoked by sensory stimulation were suppressed during long-term phase of
      sensitization and was the same as in control sensitized snails during short-term
      phase of learning. Increase in SYTO 16 fluorescence level in nucleus region site
      of LP11 neurone was completely prevented in sensitization during actinomycin D
      application. If actinomycin D was applied 30 min after sensitization (1 hour
      after first sensitizing stimulation) then synaptic facilitation and fluorescent
      dynamics was the same as in control sensitized snails. Our experimental data
      showed that nociceptive sensitization development was followed by quick (15-20
      min) DNA activation and long-term synaptic facilitation (1 hour after
      sensitization), while induction of the processes was suppressed by inhibitor of
      RNA synthesis during short time interval (during 1 hour of learning).

PMID- 15143504
TI  - [Neuroeffector connections of multimodal neurons in the African snail (Achatina
      fulica)].
AB  - Using a new method of animal preparation, the efferent connections of giant
      paired neurons on the dorsal surface of visceral and right parietal ganglia of
      snail, Achatina fulica, were examined. It was found that spikes in giant neurons
      d-VLN and d-RPLN evoke postjunctional potentials in different points of the snail
      body and viscerae (in the heart, in pericardium, in lung cavity and kidney walls,
      in mantle and body wall muscles, in tentacle retractors and in cephalic artery).
      The preliminary analysis of synaptic latency and facilitation suggests a direct
      connections between giant neurons and investigated efferents.

PMID- 15143506
TI  - [Species specificity of the isoenzyme profile of lactate dehydrogenase in organs
      of rodents of various ecogenesis].
AB  - Separation of isoenzymes of lactate dehydrogenase (LDH, EC. 1.1.1.27) in extracts
      of heart, kidney, liver, spleen, lungs of nutrias, chinchillas by agar gel
      electrophoresis reveals a species specificity in ratio of electrophoretic
      fractions of the enzyme. The isoenzymes of LDH were seem to play an important
      role in adaptation of fur animals to environmental conditions. It has been shown
      that in semiaquatic mammals--nutrias, the relative content of the A-subunits in
      the isoenzymatic spectrum of LDH in organs was increased as compared with
      terrestrial animals--chinchillas, whereas relative content of B-subunits in these
      organs of chinchillas was very high. This is an example of subtle biochemical
      specialisation of function at molecular level to environmental conditions.

PMID- 15143505
TI  - [Postcatelectrotonic potentials and trace changes in the nerve fiber
      excitability].
AB  - When cathode subthreshold impulse was turned off, excitable membranes of isolated
      nerve fibres and nervous trunk show postelectrotonic depolarisation (PED), that
      is a slow recovery of membrane potential to the resting level. PED of the single
      nodes of Ranvier and nervous trunk is registered not only in normal conditions,
      but also after complete block of sodium channels. The size and duration of
      nervous trunk PED under subthreshold depolarising current increase along with
      duration of applied depolarisation: when cathode current 1 ms in duration was
      used, they were 0.093 +/- +/- 0.004 mV and 7.123 +/- 0.576 ms, respectively; when
      current was 5 ms in duration, they were 0.189 +/- 0.005 mV and 23.212 +/- 1.186
      ms, whereas a 10-ms depolarisation yields values of 0.220 +/- 0.011 mV and 68.721
      +/- 3.389 ms. Application of the train of catelectrotonic impulses leads to PED
      built-up. As PED is found not only in normal conditions but also after complete
      block of sodium channels, it is reasonable to suggest that the most probable
      reason for PED is an outward potassium current.

PMID- 15143507
TI  - [Temperature sensitivity of the cholinergic response in cortical neurons of
      guinea pigs].
AB  - A temperature change from 20 to 36 degrees C results in a significant increase of
      neuronal responses to iontophoretic application of acetylcholine in parietal
      cortex slices. The most intensive changes in cholinergic responses occurred in
      two temperature zones: 27-29 degrees C and 34-36 degrees C. Increase in the
      responses to acetylcholine accompany with increasing spontaneous spike activity.

PMID- 15143508
TI  - [Responses of the rat kidney to the water load test and vasopressin administered
      during normal feeding and fasting].
AB  - Parameters of water-salt balance in Wistar rats were compared on empty stomach
      and at standard alimentary regimen (satiated animals). On empty stomach, the
      blood serum osmolatity amounted to 284 +/- 2, while in satiated rats--to 290 +/-
      5 mOsm/kg H2O (p < 0.05); sodium ion concentration on empty stomach lower,
      whereas no difference in potassium concentration was found. After an intragastric
      administration of water (5 ml/100 g body mass) to unanaesthetised rats, the blood
      serum osmolality decreased, while diuresis increased to an equal extent in both
      groups of rats. For 120 min after the water administration the rats on an empty
      stomach excreted 92.9% of the administrated fluid, whereas the satiated animals-
      80.7%. The urine composition differed qualitatively: in fasting rats the
      increment of diuresis was due to a rise of osmotic free water excretion, whereas
      in satiated rats--to an increase of excretion of osmotic active substances
      (including Na and K ions) with water and a simultaneous increase of the osmotic
      free water reabsorption in the kidney. After the water load and injection of
      0.005 nmole/100 g body mass of arginine-vasopressin for 2 hr of the study,
      diuresis in both groups of animals decreased to an equal extent, but in fasting
      animals this was due mostly to an increase of the osmotic free water. The data
      obtained indicate that, under conditions of usual alimentary regimen, the
      response of kidney to the water load had a character of a volume-regulating
      response, whereas in fasting rats--of the specific osmorequlating one. A problem
      is discussed of the concept of norm under usual conditions and at certain
      clinically accepted restrictions, for instance, on empty stomach.

PMID- 15143509
TI  - [Atrial natriuretic factor stimulates the frog urinary bladder osmotic
      permeability in presence of a cyclic nucleotide phosphodiesterase inhibitor].
AB  - The role of atrial natriuretic factor (ANF) in regulation of osmotic water
      permeability was studied in isolated frog Rana temporaria L. urinary bladder. It
      was found that ANF (rANF, 1-28) added to the serosal solution at concentrations 5
      x 10(-8) M and higher dosedependently stimulated the arginine-vasotocin (AVT)
      induced increase of osmotic water permeability. The effect of ANF was revealed
      only in presence of 3-isobuthyl-1-methylxantine (180 microM) and was accompanied
      by significant elevation of cGMP level in urinary bladder homogenate and isolated
      mucosal epithelial cells. C-ANF (des[Gln18, Ser19, Gly20, Leu21, Gly22]-ANF-(4
      23)-NH2), a specific agonist of NPR-C receptor, exerted no effect on osmotic
      water permeability. ANF induced a significant increase of cAMP in urinary bladder
      homogenates (AVT, 5 x 10(-11) M: 52.3 +/- 10.6; AVT + ANF, 10(-7) M: 114.2 +/-
      26.9 pmol/mg protein, n = 5, p < 0.05). The activity of adenylate cyclase in
      crude plasmatic membrane fraction was not changed. Milrinone, a specific
      inhibitor of phosphodiesterase 3, at concentrations from 25 to 80 microM,
      enhanced both the hydroosmotic response to AVT and AVT-stimulated cAMP
      production. Altogether these data demonstrate that, in the frog urinary bladder,
      ANF stimulates the AVT-induced increase of osmotic water permeability acting
      probably through NPR-A receptor-coupled mobilization of cGMP and cGMP-dependent
      inhibition of phosphodiesterase 3.

PMID- 15143510
TI  - [Sensory neurons of metasympathetic (intramural) ganglia in the guinea pig small
      intestine].
AB  - The hypothesis that multiaxonal neurons of the myenteric plexus of the small
      intestine are sensory neurons, was tested. The rising principle of the issue to
      sensory information in the metasympathetic ganglions of the small intestine was
      discovered by microapplication of the salt acid solution. Serotonin (5
      hydroxytriptamine) and acetylcholine can participate in forming primary sensory
      signals in the multiaxonal neurons. Pulsed activity in primary sensory neurons by
      mucous perfusion of the small intestine by physiological solution with pH 3.5-3.8
      was revealed. The enterochromaffin cells of the mucosa and multiaxonal neurons of
      the submucous and myenteric plexuses take part in reception of the salt acid.

PMID- 15143511
TI  - [Effect of prednisolone on the inhibition of basal gastric secretion in
      laboratory rats induced by fats or blockade of H2-receptors].
AB  - Experiments on rats with gastric fistulae for the first time have shown that
      glucocorticosteroid prednisolone causes weakening of the fat and H2-receptor
      inhibition of basal gastric secretion.

PMID- 15143512
TI  - Molecular mechanisms of apoptosis.
AB  - Apoptosis (Programmed Cell Death) is a genetically regulated, morphologically
      distinct form of cell death that can be initiated by many different physiological
      and pathological stimuli. Such strategic intracellular programming is initiated
      in many instances during normal life cycle and development in order to maintain
      the homeostasis of a multicellular organism, to eliminate unwanted cells.
      However, apoptosis is also involved in a wide range of pathologic conditions,
      including neurodegenerative and cardiovascular diseases, cancer and autoimmune
      diseases. Therefore, the ability to understand and manipulate the cell death
      machinery is an obvious goal of medical research. Here we review the basic
      components of the death machinery, discuss their interaction in regulation of
      apoptosis, and describe the main pathways that are used to activate apoptosis.

PMID- 15143513
TI  - [Proteolytic enzymes and apoptosis].
AB  - Information about basic mechanisms of programmed cell death (apoptosis)
      development with participation of proteolytic enzymes is given in the review. The
      basic mechanisms of apoptosis launching are conditionally subdivided into three
      groups, depending on the "points of application" of apoptosis development
      initiating factor: membrane (receptor-dependent), mitochondrial and nuclear.
      Attention is accentuated on ubiquitin-dependent proteasomal proteolysis as the
      key system regulating apoptosis. The possible disturbances of apoptotic program
      realization are specified under various pathological processes and diseases.

PMID- 15143514
TI  - [Vitamin E and apoptosis].
AB  - The literature data concerning the participation of tocopherol in apoptosis are
      discussed. Acting as antioxidant this vitamin exerts a complex effect on
      apoptosis mechanisms. Its action on this process is caused by involvement of some
      different mechanisms transducing the apoptotic signal. Among them are caspase and
      Fas-receptor activation, sphingosine metabolism, processes carried out in nuclei
      and mitochondria and signal transduction pathways. The specific mechanisms
      connected with interaction of this vitamin with tocopherol-binding proteins may
      be also involved in this vitamin action.

PMID- 15143515
TI  - [Kinetic and mechanism of interaction of L-cysteine with alkaline phosphatase
      from calf intestines].
AB  - The effect of L-cysteine on activity of hydrophobic forms of calf intestine
      alkaline phosphatase was investigated. Apparent inhibition constants for mixed
      type inhibition have been determined. The kinetic results allow supposing that
      the mechanism of equilibrium establishment between the inhibitor and enzyme
      involves the initial rapid formation of intermediate complex and a subsequent
      slower step leading to its stabilization in the substrate binding site. The
      microscopic rate constants for slow step of interaction of L-cysteine with
      alkaline phosphatase have been calculated. Effect of pH on apparent inhibition
      constants and kinetic parameters for enzymatic reaction in the presence of L
      cysteine was analysed.

PMID- 15143516
TI  - [Enzymes and processes of activation of the endometrium stromal cells].
AB  - The endometrium stroma cells and properties of such key enzymes as
      acetylcholinesterase, Mg2+, Ca(2+)-ATPase, AMP-deaminase have been investigated
      in them. The activity of acetylcholinesterase in suspension of cells compounds is
      9.8 +/- 0.2 mumol of tiocholinbromide/mg protein/hour and is reduced under
      influence of exogenous ATP, NO2-, H2O2 and Triton X-100. Common Mg2+, Ca(2+)
      ATPase activity of compounds of 36 +/- 2 mumol Pi/mg protein/hour, is depressed
      by sodium azide and thapsigargine, that specifies presence of an investigated
      enzyme in mitochondria and endoplasmic reticulum of investigated cells. In a
      suspension of stroma cells with addition of 0.2% of Triton X-100 for augmentation
      of permeability of cellular membranes and 1.5 M KCl for a dissociation of
      complexes AMP-deaminase with proteins and membranes, the deamination exogenous
      AMP up to IMP and NH3, is registered generated in the given response. The
      supposition about NH3 role as the paracrine regulator in the system endometrium
      myometrium of the uterus is expressed.

PMID- 15143517
TI  - [Effect of caffeine on azide-sensitive Mg2+, ATP-dependent increase of
      tetracycline fluorescent response in modeling of Ca ions accumulation in
      mitochondria].
AB  - The influence of caffeine on the Mg2+, ATP-dependent Ca(2+)-uptake was
      investigated in the experiments, conducted on mitochondria isolated from
      myometrium of nonpregnant estrogenized rats. NaN3-sensitive CTC fluorescence
      increasing (lambda f = = 520 nm) was used as a test for active Ca2+ transport.
      Kinetics of NaN3-sensitive Mg2+, ATP-dependent component of CTC fluorescence
      change fits to the pattern of the first-order reaction either in the absence or
      in the presence of caffeine (20 mM). Caffeine (0-20 mM) inhibited both the
      stationary level (settled on the 2-3d min. of incubation) and the initial rate
      V0, and rate constant k of CTC fluorescence change. Magnitude of the apparent
      inhibition constant I0.5 for caffeine is 10.41 +/- 1.81 mM, inhibition process
      has weak positive cooperativity--the value of apparent Hill coefficient for
      caffeine is equal to 1.2 +/- 0.3. Data obtained suggest that caffeine inhibits
      both stationary Ca2+ capacity of mitochondria and the rate of NaN3-sensitive
      Mg2+, ATP-dependent Ca(2+)-accumulation in case of myometrium. These data could
      be useful for further investigation of molecular and membrane mechanisms of
      caffeine action on the intracellular Ca2+ homeostasis in uterus smooth muscle and
      its contractive activity.

PMID- 15143519
TI  - [Interaction of human alpha-thrombin with organic ligands of ionic nature].
AB  - Investigations results of human thrombin interaction with organic ligands of ion
      nature containing nonpolar groups are presented. It is shown that electrostatic
      interaction is the basic one under enzyme binding, while hydrophobic binding is
      only additional function in the reaction enzyme-ligand, this fact is confirmed by
      the absence of interaction between thrombin and rivanol which has a positive
      charge side by side with cumbrous hydrophobic group. New data are presented about
      the ligand specificity of binding sites of thrombin active centre. The importance
      of relative arrangement of hydrophobic ligand groups for interaction with enzyme
      is shown. It is supposed that thrombin binding with organic ligands occurs owing
      anionic site of beta-domain of active thrombin centre with the major aminoacids
      arginine and lysine (Lys 68, Arg 78, Arg 77, Arg 66 etc.). It is shown that the
      compounds containing negative group SO3 and have some cunbours hydrophobic groups
      interact more intensively with the enzyme. Thus, rosseline--with symmetrical
      hydrophobic nucleus (four benzene rings)--is the most efficient ligand for the
      binding with thrombin. The obtained investigation results evidence for
      bacteriostatical and stabilizing effect of low-molecular asobenzene ligands on
      rather labile thrombin molecules.

PMID- 15143518
TI  - [Ligand-induced structuring of polyreactive immunoglobulins].
AB  - The influence of several hydrophobic compounds with different structures on the
      binding of native and chaotropically modified bovine immunoglobulins to native
      and denatured nonspecific protein immobilized on the surface is researched. It is
      shown that the character of binding depends on the amount and mutual location of
      hydrophobic nuclei in the effectors structure. The authors observed moderate
      suppression of binding or absence of the expressed effect while using one-nucleus
      effector. The influence of compounds with two distanced benzene nuclei differs
      qualitatively from the influence of the compound with two condensate ones,
      described earlier: it was observed that the stimulation level of the binding
      depends on structural-functional condition of immunoglobulin and immobilized
      protein. In case of the effector with three spaced hydrophobic nuclei the
      stimulating effect is much more expressed (3-4 times higher). The concentration
      dependence of the ligand-induced effects is demonstrated. It is supposed, that
      stimulative influence of effectors with spaced hydrophobic nuclei is caused by
      two different processes. The first one is the formation of highly binding center
      as the result of ligand-induced structuring of immunoglobulins. The other one is
      the competition for the center formed between dissolved polynuclear effector and
      ligand groups of aminoacids hydrophobic residues statistically formed on the
      surface of immobilized protein.

PMID- 15143520
TI  - [Effect of lipid peroxide photooxidation on activity of lymphocyte-bound
      peroxidase].
AB  - The UV-light influence (240-390 nm) in the doses range of 75.5 divided by 2265
      J/m2 has been studied on structurally functional state of lymphocytes by the
      method of determination of the TBA-active products, spectrophotometric method and
      enzyme-linked immunosorbent assay. It has been shown that UV-irradiation dose
      increase led to the intensification of lipids peroxide photooxidation processes
      on lymphocytes, accompanied by the increase of their natural peroxidase activity
      and ability to sorb exogenic peroxidase. The association of peroxidase with the
      native and UV-irradiated lymphocytes results in the decrease of its catalytic
      activity.

PMID- 15143521
TI  - [Using comet assay for the evaluation of biological activity of heavy metal salts
      in eucaryotic cells].
AB  - The test-system for the examination of different factors modifying effect on
      heavy metals biological activity was chosen. Nickel-induced DNA damage was
      examined in the chosen test-system.

PMID- 15143522
TI  - [Modulating effect of anticonvulsive agents on Ca2+ dependent membrane fusion in
      cell-free model of neurosecretion].
AB  - The effect of antiepileptic drug ethosuximide and sodium valproat on fusion of
      synaptic vesicles with synaptosomal plasma membranes was studied in cell-free
      system. It was shown that ethosuximide and sodium valproat increases the rate of
      Ca(2+)-dependent fusion reaction in vitro. We have found that convulsant drugs
      pentylenetetrazol and picrotoxin did not fuse membrane components of the model
      system. Ethosuximide- and sodium valproat-provoked fusion of synaptic vesicles
      and plasma membranes of synaptosomes were suppressed by convulsant drugs
      pentylenetetrazol and picrotoxin.

PMID- 15143523
TI  - [Activity of antioxidant enzymes in enterocytes of the small intestine and blood
      cells after ionizing irradiation and administration of vitamin E in rats].
AB  - The long-term influence of low X-ray irradiation increases lipid peroxidation
      (LP) in radiosensitive (bone marrow, enterocytes of small intenstine) and in
      relatively radioresistant blood cells (erythrocytes). The activation of
      antioxidant system enzymes in observed cells does not decrease LP intensity. We
      concluded that additional administration of alpha-tocopherol provided the
      decrease of the first and end products of LP in the observed tissues mostly in
      the beginning of the experiment. Antioxidant effect of the preparation is more
      significant in cells with high proliferative activity but normal activity of
      enzymes was not determined.

PMID- 15143524
TI  - [Mineral content of blood serum in greenland seal pups during the period of
      adaptation to the captivity].
AB  - Results of investigation of mineral levels in the harp seal pups blood serum in
      connection with adaptation to the captivity are presented. The contents of
      copper, zinc, iron, magnesium, cobalt, manganese, sodium, potassium, calcium and
      phosphorus in the first 18 day of animals keeping in the oceanarium were
      determined. The causes of the revealed differences in changes of the contents of
      single elements during the observation term, and also question on duration of
      fading stress alterations and stabilization of biochemical parameters of marine
      mammals blood are discussed.

PMID- 15143525
TI  - [Structure-functional analysis of peptide P3 identical to gamma370-383 binding
      sites with integrin alphaIIbbeta3 in gammaC-domain of fibrinogen].
AB  - The interactions between platelet integrin alpha IIb beta 3 and fibrinogen (Fg)
      mediate a range of adhesive reactions, which are necessary for platelet
      aggregation and fibrin clot retraction. The binding site for alpha IIb beta 3
      resides in the gamma C domain of Fg. In our previous work we have identified a
      novel binding site in the gamma C domain, gamma 370-383 (P3), for integrin alpha
      IIb beta 3 and have demonstrated that the P3 sequence together with the C
      terminal gamma C sequence 408AGDV411 accounts for the full binding of alpha IIb
      beta 3. In our present study, in order to define the amino acid residues in P3
      involved in the interaction with alpha IIb beta 3, we have used SPOT-synthesis
      analyses. Libraries consisting of peptides covering P3 were created and probed
      with radiolabeled alpha IIb beta 3. Screening of the libraries showed that
      several positively charged residues may be critical for interaction of P3 with
      integrin alpha IIb beta 3.

PMID- 15143526
TI  - [Interferonogenic activity of immobilized ribopolynucleotides in vitro].
AB  - In vitro experiments the authors have studied a property of yeast RNA--tilorone
      hydrochloride complex covalently linked to spheron to induce the synthesis of
      interferons type I (alpha- and beta-interferons) in the culture of peripheral
      mononuclear human cells. Such a complex is shown to possess a marked
      interferonogenic activity. The data obtained appear to be a proof of the
      interferon induction to be realised by a mechanism needing at the first stage the
      contact between the inducer and the cell surface without its penetration into the
      cell.

PMID- 15143527
TI  - [Intracellular localization of thiamine-binding proteins in the liver and kidneys
      of rats].
AB  - The distribution of thiamine-binding and thiamine triphosphatase activity typical
      of thiamine-binding proteins was studied in intracellular structures of rats
      liver and kidneys. It was found that the fraction of microsomes has the highest
      rate of specific thiamine-binding activity amide fractions of subcellular
      structures that was isolated using differential centrifugation in the both
      organs. Hydrolysis of thiamine triphosphate (pH 7.4) was also extremely active in
      these structures. The results of our research allow to make a conclusion that
      subcellular structures precipitated as fraction of microsomes (endoplasmic
      reticulum and vesicled parts of plasma membranes) are the sites of the most
      probable localisation of thiamine-binding proteins of liver and kidneys.

PMID- 15143530
TI  - [Effect of acetaldehyde on ethanol- and aldehyde-metabolising systems of the
      liver and brain of rats].
AB  - Lately the mechanism of craving for alcohol has been related to the local level
      of brain acetaldehyde occurring in ethanol consumption and depending on the
      activities of the brain and liver ethanol and acetaldehyde-metabolizing systems.
      In this connection, we studied the effect of chronic acetaldehyde intoxication on
      the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), the
      microsomal ethanol oxidizing system (MEOS) and liver and brain catalase as well
      as ethanol and acetaldehyde levels in the blood. The results showed that the
      chronic acetaldehyde intoxication did not alter significantly the activities of
      liver ADH, MEOS and catalase as well as liver and brain ALDH. In parallel with
      this, the systemic acetaldehyde administration led to shortened time of ethanol
      narcosis and activation of catalase in the cerebellum and left hemisphere, which
      may indicate involvement of this enzyme into metabolic tolerance development.

PMID- 15143529
TI  - [NO-dependent effects during adaptation of rats to intermittent hypoxia].
AB  - In experiments on Wistar rats processes nitric oxide production on concentration
      of anions (NO2-, NO3-), carbamide and polyamines contents were investigated in
      processes of rats adaptation to acute hypoxia (7% O2 in N2, 30 min) and
      intermittent hypoxia training (10% O2 in N2, 15 min, 5 cycles daily) during 14
      days. NO production by oxygen-dependent and oxygen-independent metabolites paths
      has been investigated. It is concluded that the disturbances in nitric oxide
      system induced by acute hypoxia by L-arginine injections may result in acute
      hypoxia.

PMID- 15143528
TI  - [Effect of ATP-sensitive potassium channel modulators and intermittent hypoxia on
      mitochondrial respiration during stress].
AB  - The influence of activator of ATP-sensitive potassium channels (KATP) pinacidil
      and blocker glibenclamide after intermittent hypoxia in rats under stress
      condition on ADP-stimulated mitochondrial respiration by Chance and lipid
      peroxidation processes in liver have been investigated. We used next substrates
      of oxidation--0.35 mM succinate, 1 mM alpha-ketoglutarate, 3 mM glutamate, 3 mM
      pyruvate, 2.5 mM malate and inhibitor of the mitochondrial fermentative complex I
      (10 microM rotenone), succinate dehydrogenase inhibitor (2 mM malonate) and
      inhibitor of transamination (1 mM aminooxiacetate). We suggest that adaptation by
      intermittent hypoxia and application of a KATP opener pinacidil possess
      significant protective effect on mitochondrial energy support under stress
      condition. Combination of intermittent hypoxia with pinacidil causes more
      efficient consumption of oxygen and decrease of lipid peroxidation processes
      comparative to intermittent hypoxia or pinacidil injection used separately. We
      conclude about the existence of the functional link between nitric oxide which is
      being increased under intermittent hypoxia and KATP opener. Both intermittent
      hypoxia and pinacidil effectively decrease the negative results of mitochondrial
      dysfunction under stress condition.

PMID- 15143532
TI  - [Bone segmentation in human CT images].
AB  - In 3D visualization of human skeleton, distinguishing bones from soft tissue in
      2D CT slides is the first and most critical procedure. This article presents the
      methods for image pre-processing, segmentation and smoothing. 1733 CT images of
      human body from Visible Human Project provided by the American National Library
      of Medicine are treated in this paper. We use the technique of Chebyshev uniform
      approximation filtering for denoising and present a new simple adaptive threshold
      method in segmentation, which combines the similarity of consecutive slices with
      the region-growing method. In post-processing, we use the algorithms of
      mathematical morphology and multi-resolution filtering. The accuracy of
      segmentation is examined and certified by comparing the segmented images with the
      original one. The results also demonstrate a wide applicability of the method.

PMID- 15143531
TI  - [Retrospective analysis of the effect of Ukraine and USA research interrelations
      on the development of sport biochemistry in the XX century].
AB  - This review highlights some of the important developments in Sport Biochemistry
      and relates these endeavors to the current understanding of muscle biochemistry
      and function. Attempts have been made to establish some scientific links involved
      in the evolution of such research, in particular the influences shared by
      scientists working in some premier institutions in Ukraine and the USA in the
      20th century. Research initiated in the United States by Sutherland lead to
      further Ukrainian investigations that aided in the understanding of the role cAMP
      and cAMP-dependent protein kinase in muscle metabolism during exercise. Topics
      covered include Palladin's pioneering research on muscle creatine in Ukraine at
      the beginning of the 20th century, Russian program on creatine supplements in the
      1970s-1980s and its implementation at Olympic games.

PMID- 15143533
TI  - [Preparation and degradation of poly(DL-lactide)/calcium phosphates porous
      scaffolds].
AB  - The porous foams were prepared by the solvent-casting and particulate-leaching
      technique using poly(DL-lactide) (PDLLA), poly(DL-lactide)/hydroxyapatite
      (PDLLA/20wt%HA), and poly(DL-lactide)/beta-tricalcium phosphate(PDLLA/20wt% beta
      TCP) respectively. Observations by scanning electron microscopy indicated that
      the HA and beta-TCP were homogeneously dispersed in the polymer matrix, and the
      pores of the foams are interconnected, resulting in continuous pore structures.
      The porosity of PDLLA/HA and PDLLA/beta-TCP foams was lower than that of the pure
      PDLLA foams, but the compression strength was higher than that of the pure PDLLA
      foams. The results of the degradation in vitro showed that both HA and beta-TCP
      had significant inhibitory effects on the degradation of PDLLA, especially the
      HA. It is expected that the composite foams are of use as scaffolds for bone
      tissue engineering.

PMID- 15143535
TI  - [Blood compatibility of two novel polyurethane coating materials].
AB  - Amphiphilic coupling-polymer of stearyl poly (ethylene oxide)-co-4, 4'
      methylendiphenyl diisocyanate-co-stearyl poly(ethylene oxide), MSPEO, was
      specially designed as surface-modifying additives. The blends of MSPEO in both
      polyether urethane (PEU) and chitosan(Chi), as the coating materials for
      intravascular device were investigated. Two kinds of static clotting time tests,
      plasma recalcification time (PRT) and prothrombin time(PT), as well as the static
      platelet adhesion experiment were carried out. And the dynamic anti-coagulation
      experiment was performed with a closed-loop tubular system under a blood shear
      rate of 1,500 s-1. The results demonstrate that both blend coatings can improve
      the anti-coagulation of polyurethane greatly and will not lead to hemolysis, and
      that more platelets adhere to the surface modified by Chi-MSPEO blend coating as
      compared with those adhere to the surface modified by PEU-MSPEO blend coating.
      The surface modified by Chi-MSPEO has longer PRT, whereas the surface modified by
      PEU-MSPEO has longer PT.

PMID- 15143534
TI  - [Correlative changes of histomorphometry and biomechanical property of lumbar
      vertebrae body in ovariectomized rats].
AB  - This paper presents the correlative changes of cancellous bone histomorphometry,
      biomechanical property and bone mineral contents of lumbar vertebrae in
      ovariectomized rats. Forty eight 10.5-month-old female SD rats were randomized to
      six groups: 1) Basal: at 10.5 mon. of age; 2) sham-1: sham-operated at 13 mon. of
      age; 3) OVX-1: ovariectomized at 13 mon. of age; 4) sham-2: sham-operated at 16
      mon. of age; 5) OVX-2: ovariectomized at 16 mon. of age; and 6) OVX-2 + EE:
      ovariectomized and treated with 17 alpha-ethynylestradiol (100 micrograms.kg-1.d
      1) starting at 13 mon. of age for 12 weeks. Double in vivo fluorochrome labeling
      was administered to all rats. At the end-point of study, the undecalcified
      longitudinal fourth lumbar vertebra (LV4) sections were cut and stained with
      Goldner's Trichrome for bone histomorphometric analyses. The mechanical
      properties of the compact fifth lumbar vertebra body (LV5) were measured with
      compression test, the LV5 bodies then were dried constantly with high temperature
      and digested with acid for testing of bone mineral content. A trend in trabecular
      bone volume (BV/TV), trabecular thickness (Tb.Th) of LV4, bone break load, break
      stress, elastic moduli and bone calcium content of LV5 to increase with the
      increase of age was revealed in the intact rats, but the highest value was at 13
      mon. of age. A positive correlation was seen between histomophormetry and bone
      bio-mechanical properties in the intact rats. Compared with the data from the
      sham-operated rats, the BV/TV and Tb. Th significantly decreased and bone
      turnover rate significantly increased in OVX rats at 10 weeks, and the above
      parameters further decreased 22 weeks post OVX. Correspondingly, the bone break
      load, break stress, elastic moduli and bone calcium content significantly
      decreased with the increase of time post OVX was compared with those of sham
      operated rats. A positive correlation between histomophormetry and bone
      biomechanical properties was also observed in OVX rats (r = 0.399, P = 0.018).
      Bone histomorphometry is good for predicting early physiological and pathological
      changes and bone biomechanical properties are good parameters for predicting
      corresponding function of bone such as fracture. Both of them are useful and
      needful in the animal studies on osteoporosis and related pharmacodynamic
      observations on new drugs.

PMID- 15143536
TI  - [DNA microarray reveals changes in gene expression of endothelial cells under
      shear stress].
AB  - cDNA microarray technology is used as a powerful tool for rapid, comprehensive,
      and quantitative analysis of gene profiles of cultured human umbilical vein
      endothelial cells(HUVECs) in the normal static group and the shear stressed (4.20
      dyne/cm2, 2 h) group. The total RNA from normal static cultured HUVECs was
      labeled by Cy3-dCTP, and total RNA of HUVECs from the paired shear stressed
      experiment was labeled by Cy5-dCTP. The expression ratios reported are the
      average from the two separate experiments. After bioinformatics analysis, we
      identified a total of 108 genes (approximately 0.026%) revealing differential
      expression. Of these 53 genes expressions were up-regulated, the most enhanced
      ones being human homolog of yeast IPP isomerase, human low density lipoprotein
      receptor gene, Squalene epoxidase gene, 7-dehydrocholesterol reductase, and 55
      were down-regulated, the most decreased ones being heat shock 70 kD protein 1,
      TCB gene encoding cytosolic thyroid hormone-binding protein in HUVECs exposed to
      low shear stress. These results indicate that the cDNA microarray technique is
      effective in screening the differentially expressed genes in endothelial cells
      induced by various experimental conditions and the data may serve as stimuli to
      further researches.

PMID- 15143537
TI  - [Effects of the variation in components of DLC on protein adsorption].
AB  - Diamond-like carbon(DLC) was prepared by means of plasma source ion implantation
      ion beam enhanced deposition. Through the heat treatment upon DLC in air and in
      depressed Ar gas, the DLC rich in graphite, DLC rich in diamond, and other kinds
      of DLC used in the study were obtained respectively. For the three kinds of DLC,
      the components of carbonaceous phase were analysed by X-ray photoelectron
      spectroscopy (XPS), the adsorptive amounts of human serum albumin (HSA), human
      serum fibrinogen (HFG) and human serum immunoglobin (IgG) on their surfaces in
      the condition of constant temperature were determined by radio isotope 125I
      labelling method. Results showed the graphite phase and diamond phase in DLC
      increased by two times or so respectively after the aforementioned different heat
      treatment. In pace with the increase of these foreign phases, the adsorptive
      amounts of HFG and IgG on DLC greatly increase but the adsorptive amounts of HSA
      on DLC decrease; furthermore, there is a change from non-selective adsorption of
      three human serum proteins into selective adsorptions of HFG and IgG prior to
      HSA. These results indicate that the foreign phases in DLC such as graphite,
      diamond, C-H phase and C-O phase have a great effect on protein adsorption on DLC
      and hence a negative effect on the hemocompatibility of DLC. The mechanisms for
      the increase of graphite phase and diamond phase in the process of heat treatment
      were also discussed in this paper.

PMID- 15143538
TI  - [Three-dimensional finite element stress analysis on the periodontal tissue of
      maxillary canine].
AB  - A three-dimensional finite element model of the maxillary canine was developed
      including periodontal ligament, pulp and alveolar bone. And the stress
      distributions in the periodontal tissue were obtained under different orthodontic
      force. The specific aims were to make the model by means of the more advanced and
      accurate twin CT, to provide more accurate data for clinical use, and to build a
      more accurate model for the simulation of maxillary canine movement under
      orthodontic forces.

PMID- 15143539
TI  - [Evaluation on biocompatibility of Ti-Fe-Mo-Mn-Nb-Zr alloy].
AB  - In this study, the general toxicity tests including acute toxicity test,
      haemolysis test, MTT assay of Ti-Fe-Mo-Mn-Nb-Zr alloys were carried out. The
      morphology of these cells was also observed under phase-contrast microscope. By
      using X-ray photoelectron spectroscopy(XPS), the kind and mol% of element in
      surface film were studied. The kind and concentration of element in dipping fluid
      were investigated by ICP atomic emission spectrometry. The results showed the
      primary component is TiO2 in surface film. The dipping fluid of Ti-Fe-Mo-Mn-Nb-Zr
      alloys contains Fe 0.2-1.07 mg/l and Mn 0.16-0.5 mg/l; such dental materials are
      beneficial to health. No cytotoxic effect was disclosed by in vitro and in vivo
      tests. The level of cytotoxicity was grade 0 and 1; the haemolysis degree was
      0.558%-0.642%, i.e. less than 5%. The cells growing in the extract showed normal
      morphology. These data indicate that Ti-Fe-Mo-Mn-Nb-Zr alloy, as a dental
      material, has good biocompatibility.

PMID- 15143540
TI  - [Changes of compliance in tensional anastomotic arteries].
AB  - The data of arterial pressure and diameter were measured in vivo before and after
      normal anastomosis and tensional anastomosis in canine femoral arteries at
      different time intervals. The arterial compliance was calculated, and the
      exponential form C = bemPa was employed to fit the compliance (C)- average
      pressure (Pa) curve. The relationship between compliance and average pressure was
      determined. The results showed that the compliance of arteries decreased after
      anastomosis, and the compliance of arteries after tensional anastomosis was lower
      than that of normal anastomosis at different time intervals. It was decreased
      most markedly at 14 days after tensional anastomosis. This indicated that the
      distensibility of tensional anastomotic artery was decreased more markedly than
      that of normal anastomotic artery. The function of artery was evidently affected
      by tensional anastomosis.

PMID- 15143541
TI  - [Application of oligo-microarray in an in vitro study of the effects of pulsatile
      fluid shear stress on gene expression of human smooth muscle cells].
AB  - We assessed the effects of pulsatile flow shear stress on the gene expression
      profiles of human umbilical artery smooth muscle cells (HUASMCs) in vitro using
      the Express Chip DNA microarray method and investigated the difference between
      pulsatile and steady shear stress on differentially expressed genes of HUASMCs.
      In a modified pulsatile flow chamber system, HUASMCs were exposed to pulsatile
      and steady fluid shear stress (5.52 dyne/cm2) for 6 h respectively, and normal
      static cultured HUASMCs were selected as a control. The total cellular RNA was
      extracted by TRIzol Reagent (Life Technologies, Inc) according to the
      manufacturer's manual. Conversion of mRNA to single strand cDNA and double strand
      cDNA template was synthesized by Reverse Transcription from the total RNA. cRNA
      probe was transcribed with biotin labeling. After hybridization of probe with
      microarray, the binding of streptavidin to biotin was performed and amplified
      with the first antibody and further amplified with Cy3-conjugated second
      antibody. Then detection of Cy3 dye was carried out with ScanArray 5000. The
      results showed that a total of 1,330 genes revealed differential expression in
      HUASMCs exposed on pulsatile shear stress (5.52 dyne/cm2, 6 h); however, 2,676
      genes revealed differential expression in HUASMCs exposed on steady shear stress.
      Comparsion of HUASMCs exposed to pulsatile with the HUASMCs exposed to steady
      shear stress showed there were 2,297 genes revealing differential expression. The
      transcriptional profile of fluidally induced genes in HUASMCs suggested a
      different response to pulsatile and steady shear stress.

PMID- 15143542
TI  - [Extraction of sleep structure information from heart rate variability based on
      spectrum analysis].
AB  - In this study we made full use of the heart rate spectrum analysis to obtain the
      character parameters of heart rate variability related to EEG sleep phase
      information, and then we discarded the correlation between characteristics by
      employing Principal Component Analysis. Finally, by means of the decision tree
      based on Fisher rules, we established two full automatic models for identifying
      healthy people and sleep apnea hypopnea syndroma (SAHS) patients respectively.
      The result of experiments indicates that the model is accurate and robust.

PMID- 15143543
TI  - [Fast volume rendering of echocardiogram with shear-warp algorithm].
AB  - Shear-warp is a volume rendering technology based on object-order. It has the
      characteristics of high speed and high image quality by comparison with the
      conventional visualization technology. The authors introduced the principle of
      this algorithm and applied it to the visualization of 3-D data obtained by
      interpolating rotary scanning echocardiogram. The 3-D reconstruction of the
      echocardiogram was efficiently completed with high image quality. This algorithm
      has a prospective application in medical image visualization.

PMID- 15143544
TI  - [Study on the influence of simulative EEG modulation magnetic field on the
      discharge of median raphe nuclei].
AB  - In this paper the response characteristic of the nerve fiber to the modulation
      magnetic field induction is studied by using the method of numeric simulation. It
      is found that the nerve fiber is sensitive to the low frequency modulated signal
      but not to the high frequency carrier wave. A simulative EEG signal generator is
      developed according to the change of EEG rhythm during the sleep. The simulative
      EEG square wave is modulated by high-frequency magnetic impulse. The modulation
      magnetic field is coupled into the rabbit's brain to study the influence of
      magnetic stimulation on the discharge of 5-hydroxytryptamine (5-HT) nerve cell.
      The experiment results demonstrate that discharge frequency of median raphe
      nuclei related to sleep changes significantly and the discharge becomes slow,
      which shows that magnetic stimulation can inhibit electrical activity of 5-HT
      nerve cell and provide a new way to improve insomnia.

PMID- 15143545
TI  - [Study on the preparation of folate-conjugated albumin nanoparticles].
AB  - Bovine serum albumin nanoparticles(BSANP) were prepared by desolvation method.
      The activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjuated
      to the surface of BSANP via the amino groups. Then the folate-conjugated BSANPs
      (folate-BSANP) were purified with Sephadex G-50 column and completely separated
      from unreacted folic acid. After chymotryptic hydrolysis, the extent of folate
      conjugation on the BSANP was determined by quantitative ultraviolet(UV)
      spectrophotometric analysis. It was found that the spectrum of trypsin digest of
      folate-conjugate BSANP is basically identical with that of folate, thus
      indicating folate is successfully expressed on the surface of BSANP. The folate
      BSANP was averagely 66 nm in diameter and was spherical in shape. Folate
      conjugated BSANP was achieved, which represents a potential new drug carrier for
      tumor cell-selective targeting.

PMID- 15143546
TI  - [Air distribution in the bronchial tree of human lungs].
AB  - A three-element model of lumped parameter based on the statistic data of Weible's
      symmetric model and on the reference anatomic figures of the bronchial tree of
      the lungs has been proposed using the fluid network theory. It was assumed that
      the upper five or seven generations of the twenty-four generations of the
      respiratory airway are asymmetric, while the rest are symmetric. GEAR method was
      used to solve the ordinary differential equations. The pressure and flow rate
      distributions in different positions of the lungs during normal respiration and
      partial bronchial obstruction were compared, respectively. This model has great
      significance in finding out the air distribution in the human bronchial tree
      under various physiological and pathological conditions.

PMID- 15143548
TI  - [Oxygen transport in pulmonary capillaries].
AB  - Based on the principles of the sheet-flow model, oxygen transport in pulmonary
      capillaries was considered as a process in which oxygen first enters plasma
      through the respiratory membranes, and then combines with the Hbc. A novel
      mathematical model about oxygen transport in pulmonary capillaries was
      established according to the relationship of the oxygen concentration inside the
      red blood cells with the concentration of haemoglobin and the blood saturation,
      and according to the basic formula for the correlation between blood saturation
      and oxygen partial pressure. Furthermore, we adopted the Lax-Wendroff Finite
      Difference Method and obtained certain valuable results under different
      physiological states. It was well concluded that the established model could be
      used to provide useful data for medical researchers as well as doctors.

PMID- 15143547
TI  - [The influence of IL-3 on the differentiation and development of dendritic cells
      from mouse bone marrow].
AB  - In order to compare the effects of GM-CSF + IL-4 with the effects of IL-3 + IL-4
      on the differentiation and development of dendritic cells (DCs) from mouse bone
      marrow, we cultured bone marrow hematopoietic progenitor cell in vitro and
      examined whether DCs induced by IL-3 + IL-4 (IL-3 DCs) differed from the DCs
      induced by GM-CSF + IL-4 (GM-CSF DCs) in morphology, yields, phenotype and
      endocytic activity. Scanning electron microscope, laser scanning confocal
      microscope (LSCM) and flow cytometer (FCM) were used. The results showed that the
      DCs induced by IL-3 + IL-4 and the DCs induced by GM-CSF + IL-4 had similar
      morphology, and the DCs induced by IL-3 + IL-4 expressed high level of major
      histocompability complex (MHC) class II. Besides, IL-3 DCs had the
      characteristics of higher yields and better consistency. But CD80 and CD86 were
      expressed at low levels or absent on IL-3-treated DCs. The capability of uptaking
      antigen of IL-3 DCs was more powerful than that of GM-CSF DCs. IL-3 could
      substitute for GM-CSF in culturing DCs from mouse bone marrow cells and could
      obtain the tolerance DCs that lack costimulatory molecules.

PMID- 15143549
TI  - [Spatial spectra of neural electric activities and their application in study of
      visual spatial selective attention].
AB  - In this paper, the spatial spectra of neural electric activities and their
      primary application to visual spatial selective attention are presented. Based on
      the spherical harmonic spectra inversion by equivalent distributed dipole layer
      technique, novel latitude spectra S(1) and longitudinal spectra S(m) are defined
      as the description of spatial spectra of brain electric activities. When the
      latitude and longitudinal spectra are applied to the event-related potentials
      (ERP) of spatial selective attention to the right and left visual fields, the
      temporal structures of spatial spectra of all temporal sample points show
      meaningful delay and amplitude differences of components between 100 ms and 200
      ms for attended and unattended stimulus conditions. These facts indicate that the
      latitude and longitudinal spatial spectra concept is useful in study of cognitive
      brain research.

PMID- 15143550
TI  - [Biological characteristics of human embryonic myoblasts in vitro].
AB  - This study was intended to observe the biological properties of primary human
      embryonic skeletal myoblasts cultured in vitro and to inquire about the possible
      differentiation mechanism. Isolated human embryonic myoblasts were identified by
      morphology and myosin immunohischemical staining. The proliferating myoblasts
      were shifted to DM (DMEM supplemented with 3% fetal bovine serum) to induce
      differentiation. The control group was cultured in GM (DMEM supplemented with 10%
      fetal bovine serum). The differentiation was tested by the rate of myotube
      formation (RMF); The change of cell cycle was tested by flow cytometry; the
      morphological features were observed by use of inverted microscope and TEM. The
      myogenic regulatory factors (MRFs) such as MyoD, Myogenin and Myf5 were assayed
      by RT-PCR. Results showed that the primary myoblasts cultured in DM, in
      comparison with those cultured in GM, had higher rate of myotube formation (RMF)
      and myofilament formation, and more of the myoblasts cultured in DM exited the S
      phase. The expression level of Myogenin mRNA was obviously higher than that of
      the control group, the increase of MyoD mRNA expression level was not so high,
      however, the expression of Myf5 mRNA was decreased. These data indicate that
      there is a possible mechanism between differentiation and cell cycle. Besides,
      the mRNA expression of myogenic regulatory factors (MRFs) occurs in different
      phase of differentiating myoblastes and implicates the diverse biological
      function.

PMID- 15143551
TI  - [Expression and purification of mouse B lymphocyte chemoattractant].
AB  - A DNA fragment encoding mouse B Lymphocyte Chemoattractant (BLC, MV10Kda) was
      obtained by PCR. The amplified fragment was inserted into prokaryotic expression
      vector PQE30. Recombinant protein was expressed in E. Coli XL-1 blue and purified
      by affinity chromatography on a nickel-nitrilotriacetic acid gel matrix. Then it
      was identified by sequence analysis and Western blot analysis. The fragment
      inserted into prokaryotic expression vector PQE30 was identified to be BLC gene
      fragment by sequence analysis. And a specfic band was shown by Western blot
      analysis. These findings provide the evidence that the recombinant protein
      obtained and purified in this study using gene engineering method is mouse B
      Lymphocyte Chemoattractant.

PMID- 15143552
TI  - [Cloning and expression of immunoadjuvant molecule--CTB gene].
AB  - We cloned cholera toxin subunit B gene from 569B and M045 strain of Vibrio
      cholerae with polymerase chain reaction, constructed recombinant plasmid pCTB,
      and transformed pCTB into the prokaryotic cell strain JM109. The indentification
      was made by means of restriction enzyme analysis, polymerase chain reaction, DNA
      sequencing, SDS-polyacrylamine gel electrophoresis analysis and Western blot. The
      results indicate that we have amplified cholera toxin subunit B gene of 376 bp
      from Vibrio cholerae and hve constructed the recombinant plasmid pCTB, and we
      have affained the object amied at successful expression of 12 KD in the
      prokaryotic cell strain.

PMID- 15143553
TI  - [Preparation of chitosan-collagen sponge and its application in wound dressing].
AB  - We have prepared a wound dressing made from chitosan and collagen. Its clinical
      curative effect was detected. Chitosan solution was put into purified collagen
      solution. Then, the solution became sponge by means of freeze drying, and it was
      subjected to a series of toxicology tests, including acute toxicity, stimulation
      test, allergic and hemolysis tests, as well as the clinical test of openning
      trauma in orthopedics. All of the results of toxicology tests were negative. The
      chitosan-collagen sponge could not only accelerate the speed of curing but also
      restrain the extravasate. Therefore, the chitosan-collagen sponge has good
      biocompatibility and clinical curative effect. It is a prospective security
      biomaterial for medical use.

PMID- 15143554
TI  - [Bio-tribological properties of dental prosthesis made of nitriding titanium
      alloy material].
AB  - Titanium alloy material (TC4) samples were treated with nitriding technique. The
      dynamic friction and wear behavior of the modified layer were examined on a
      reciprocating sliding rig in artificial saliva. Microhardness, depth profile and
      wear mechanisms were investigated by means of MVK-H12, TALYSURF6, XPS and
      microscopy. The results demonstrate that after being treated with nitriding
      technique the titanium alloy material (TC4) has better tribological behavior and
      up-graded wear resistance. The wear mechanism involves adhesion.

PMID- 15143555
TI  - [Extracellular matrix for the replacement of ureteral defect].
AB  - This is an experiment on rabbits to evaluate the possibility of ureteral
      replacement by extracellular matrix. We adopted a biochemical method for
      preparing a new tissue engineering material named Extracellular Matrix (ECM), and
      the ECMs were used as homologous grafts to replace the defect in the ureters.
      Light microscopy, scanning electron microscopy, immunohistochemical technique and
      intravenous urography were used. The routine blood and biochemical laboratory
      tests were made before and after operation, and the measured values of pressure
      in the ureter of experiment and control groups were compared. The ureteral ECM
      was found in the experiment to promote the regeneration of all ureteral wall
      components. There were no significant differentces between the regenerative
      tissue and the normal tissue in morphology and function 16 weeks after
      replacement. The homologous ECM might be an ideal replacement material for
      ureteral defect.

PMID- 15143556
TI  - [Assessing the transvalvular gradient of a Chinese-made jiuling solid pyrolytic
      carbon bileaflet heart valve prosthesis].
AB  - In order to assess the transvalvular gradient of a Chinese-made Jiuling solid
      pyrolytic carbon bileaflet heart valve prosthesis, we determined its
      hydrodynamics in the laboratory and then measured the hemodynamic performance in
      the animals and patiens. The Jiuling prosthesis was tested in a pulsatile flow
      simulator in the aortic position. Six sheep subjected to mitral replacement with
      21 mm Jiuling prosthesis were measured by open cardiac catheterization
      intraoperatively. Doppler echocardiography and open cardiac catheterization under
      dobutamine stress were performed in two sheep 60 months after implantation.
      Clinically, 14 cases of aortic valve and 10 cases of mitral valve in the patients
      who underwent valve replacement with Jiuling heart valve prosthesis were measured
      by open cardiac catheterization and Doppler echocardiopgraphy. The results showed
      that Juiling heart valve prosthesis had lower mean transvalvular gradient (below
      10 mmHg) at any given tissue annulus diameter. In animal experiments, the
      transvalvular gradients of 6 sheep were 5.2 +/- 1.7 mmHg intraoperatively, and of
      2 sheep 60 months after implantation were 6.1 +/- 0.3 mmHg by catheterization. In
      patients, the mean transvalvular gradients in the aortic position measured by
      means of catheterization and echocardiography were 6.26-4.10 mmHg and 9.42-7.48
      mmHg; the gradients in the mitral position were 2.10-1.9 mmHg and 5.281-4.10 mmHg
      respectively. The above results demonstrate that Jiuling valve prosthesis has
      excellent hemodynamic performance.

PMID- 15143557
TI  - [Construction of LACK gene recombinant plasmid and detection of its expression in
      eukaryotic cell].
AB  - The LACK gene from Leishmania, an analogue of the receptor of activated protein
      kinase C, was discovered recently. In this study, the LACK gene of Leishmania
      donovani was obtained from the recombinant plasmid T-LACK by PCR. The gene was
      cloned into eukaryotic expressed plasmid pcDNA3.1(+) to construct recombinant
      plasmid. This recombinant plasmid then was transfected into the eukaryotic cell
      COS-7, and the expression of LACK gene in eukaryotic cell was detected by RT-PCR
      and immunofluorescent staining. Both RT-PCR and immunofluorescent staining of
      recombinant plasmid transfected COS-7 showed positive reaction, thus indicating
      that the recombinant plasmid pcDNA3-LACK can express LACK protein in euka ryotic
      cell COS-7.

PMID- 15143558
TI  - [High cholesterol level upregulate the expression of caveolin-1].
AB  - To study the influence of hypercholesterolemia with caveolin-1 on the plasmalemma
      of vascular endothelium, we used the methods of immunohistochemistry to detect
      the dynamic changes of caveolin-1 in cultured ECV-304 cells which were stimulated
      high cholesterol serum and the arterial endothelium of hypercholesterolemia rats.
      It is resulted that high cholesteorol level can upregulate the expression of
      caveolin-1 both in vitro and in vivo. In the initial stage of
      hypercholesterolemia model, the expression of caveolin-1 increased as the time of
      high cholesterol level added, but in the later period it was decreased slightly.

PMID- 15143559
TI  - [Digital fluoroscopy imaging system with dual energy X-ray image decomposition].
AB  - Dual-kilovolt technique was realized in dual energy X-ray imaging system with
      computer controlled KV adjustment, filter switching and image acquirement. The
      dual energy images can be obtained in 2-3 seconds to avoid moving artifact. Low
      energy photons in high energy X-ray beam can be attenuated effectively by a 2 mm
      Cu filter to separate the spectra of the high and low energy X-rays. A simplified
      dual energy decomposition method was used to obtain the soft tissue image. An
      example of chest dual energy radiographs is presented to illustrate the
      performance of the system.

PMID- 15143560
TI  - [Research on the application of neural network to diagnosis of cardiopathy].
AB  - Neural networks can fit any nonlinear function. After drawing out several
      characteristic parameters from the three-dimension spectrum for high frequency
      QRS waves, we input them into the network and trained the network. In this way,
      we can get a m-dimension curved surface in the m-dimension space which is
      constructed by those parameters, and this curved surface divides the space into
      two parts: the unhealthiness and the health. Now, the network can automatically
      distinguish between the healthiness and the unhealthiness according to their
      three-dimension spectrum for high frequency QRS waves.

PMID- 15143561
TI  - [The development of an active shimming system for 0.2T open-style permanent
      magnet MRI].
AB  - This paper introduces the basic structure, operation principle as well as
      shimming method of an active shimming system, which was developed for 0.2T open
      style permanent magnet MRI. In the end, a group of spin-echo images (T1 weighted
      and T2 weighted) produced by the 0.2T MRI are given to demonstrate the
      satisfactory shimming performance of this active shimming system.

PMID- 15143562
TI  - [Three-dimensional finite element study on middle face advancement with
      distraction osteogenesis].
AB  - Based on the anatomic structure of a girl with class III skelet al malocclusion,
      a three-dimensional finite element biomechanical model of facial soft tissue was
      established. With the use of this model, three surgery plans of distraction
      osteogenesis, LeFort I, II, III maxillary complex advancement in the direction of
      functional occlusal plane, were simulated. As a result, the facial soft tissue
      deformation was predicted and the ratio of the facial location deformation to the
      free bone advancement was calculated. The facial shape after surgery could be
      viewed in 3D. In addition, the location of center of resistance was investigated
      when the free bone was protracted forward in the process of LeFort I maxillary
      complex advancement; it was located at a site about 30 mm posterior to the soft
      tissue A point. The research result indicates that three-dimensional finite
      element research on distraction osteogenesis can provide instruction for setting
      the suitable protraction point and direction of the protraction force in surgery,
      and by predicting the facial soft tissue deformation, it also can provide the
      surgeon and patient with information on the options and reference to the surgery
      plans.

PMID- 15143563
TI  - [Pumping performance of a new piezoelectric pump for drug delivery].
AB  - A novel double-chamber series piezoelectric pump has been presented and tested.
      The pump is a multi-layer circular planar structure, consisting of PMMA
      (polymethyl methacrylate) pump body, two PZT actuator membranes and three
      cantilever valves. The PZT actuators are driven at a phase difference of 180
      degrees, which is equal to two one-chamber pumps running in series. The output
      performance depends on the geometrical parameters of the actuator membrane. The
      prototype pump, fabricated with the PZT membrane 0.18 mm in thickness and 50 mm
      in diameter of 50 mm, can deliver drug in either direct way (pumping liquid drug)
      or indirect way (pumping air to extrude liquid drug from a sealed container). The
      frequency-response characteristic of the two handling methods is of difference.
      The pump obtains optimum performance at low frequency for liquid as medium, and
      at high frequency for air as medium. For both the direct delivery and indirect
      delivery, the maximum flowrate achieved reached up to 220 ml/min and 35 ml/min,
      respectively; and the maximum backpressure obtained amounted to about 14 KPa and
      21 KPa, respectively, at the applied voltage of 80 V with frequency of 20 Hz.

PMID- 15143564
TI  - [Study on medical diagnosis decision support system for heart diseases based on
      hybrid genetic algorithm].
AB  - In this study, a medical diagnosis decision support system based on hybrid
      genetic algorithm has been established to support the diagnosis of five common
      heart diseases (coronary heart disease, rheumatic valvular heart disease,
      hypertensive heart disease, chronic cor pulmonale and congenital heart disease).
      A heart disease database consisting of 352 samples was used for constructing and
      testing the performance of system. Cross-validation of the experimental results
      indicate that the system we established shows high capability of classifying
      these five kinds of heart diseases, the mean accuracy of classification is as
      high as 90.6%, and the user accuracy and procedure accuracy of each disease are
      both above 85.0%, showing great application prospect of supporting heart diseases
      diagnosis in clinics.

PMID- 15143565
TI  - [Computer-assisted surgical navigation technique].
AB  - Surgical navigation system is a system that processes medical images by computer
      graphics and image processing technique, reconstructs 2D or 3D medical image
      models. It builds a real-time loop among the eyes of doctor, the surgical device
      and the head of patient by several of space localization technique, so that to
      realize displaying the localization of surgical devices real-time. The history
      and research status of surgical navigation system is summarized and the system
      configuration and the key techniques are expatiated emphatically in this paper.
      The key techniques include localization in space, image processing and displaying
      technique, system registration technique and head location technique. At last the
      progress direction of navigation systems is given.

PMID- 15143566
TI  - [Factors controlling the microstructure of collagen-based dermis regeneration
      scaffold].
AB  - The factors controlling the microstructure and properties of collagen-based
      bioactive artificial dermis are reviewed. The second component, the pore diameter
      and porosity, the thickness of scaffold, the bioactive factors as well as the
      cross-linking density that are important parameters of artificial dermis should
      be carefully researched and designed. Experiment methods controlling these
      parameters are suggested.

PMID- 15143567
TI  - [Advances in piezoelectric quartz crystal biosensor and its applications].
AB  - Piezoelectric quartz crystal biosensor is a new sensor developed with the
      comprehensive utilization of the high sensitivity to mass and the surface
      characteristics of quartz crystal such as density, viscosity, dielectric
      constant, conductance, and the high specificity of biologic identification
      molecules. It has the features of high sensitivity, high specificity, simple
      operation, high analysis speed, low cost, small size, on-line detection, etc. It
      can be of wide application in the areas of medical laboratory diagnosis,
      environment monitor, foods sanitary control and industrial production. In this
      paper, the fundamental principle, structure and its applications are reviewed.

PMID- 15143569
TI  - [The progress in epileptic seizure prediction].
AB  - It is estimated that epilepsy, a chronic disorder of the nervous system, affects
      about 0.5%-2% of the population and about 10%-50% do not respond well to current
      antiepileptic medications and may not be candidates for surgery. For these
      patients, the unpredictability of seizure onset is a major cause of disability
      and mortality. Therefore, anticipation of an imminent seizure would be beneficial
      to patients because it could provide time for the application of preventive
      measures to keep the risk of seizure to a minimum. This paper reviews the
      feasibilities, the progress, existing problems and possible applications in the
      field of epileptic seizure prediction.

PMID- 15143568
TI  - [The influence of biodegradable polymer on bone and soft tissue].
AB  - Clinical and research reports concerning orthopedic biodegradable implants were
      reviewed. The clinical results were analyzed in terms of complications and
      compatibility. The possible applications of the implants and further research
      fields were summarized.

PMID- 15143571
TI  - [Nanotechnology & nanoparticles and their advances of investigation and
      application in the fields of biomedicine].
AB  - Nanotechnology is the technique that is used in manufacturing special function
      products with the studies of movement regularities and properties for electrons,
      atoms and molecules within 1-100 nm. It is penetrating into the fields of biology
      and medicine. Because nanoparticles possess quantum size effect, surface little
      size effect and grand quantum tunnel effect, they exhibit many characteristics
      such as great specific surface area, high surface activity, a lot of surface
      active centers, high catalytic efficiency and strong adsorbing ability. The
      development of biology and medicine will be speeded up with the progress of
      nanotechnology and the understanding of nanoparticles.

PMID- 15143570
TI  - [Basic researches on cell adhesion and its application in tendon tissue
      engineering].
AB  - Cell adhesion is a basic and very important tissue in the field of tissue
      engineering. Fibronectin and integrins are the most important elements to cell
      adhesion. Some surface receptors of fibroblast can also conjugate with type I
      collagen in extracellular matrix (ECM) directly. Laminin receptors on the surface
      of fibroblast bound to laminin also play a role in cell adhesion. In this paper
      are reviewed a number of related articles. The structures and function of
      fibronectin and integrins are discussed in detail; the tendon cell's adhesion
      structures are also discussed. Yet, there was scarcely any paper on the effects
      which the preservation of tissue engineered products may have on cells' adhesion
      fo ECM. Therefore, researching on cell adhesion and finding a way of preservation
      that has no or very little adverse effect on cell adhesion is an important topic.
      Results from expected advanced researches on cell adhesion may probably find
      promising applications in the field of tissue engineering.

PMID- 15143572
TI  - [Models and computation methods of EEG forward problem].
AB  - The research of EEG is of grat significance and clinical importance in studying
      the cognitive function and neural activity of the brain. There are two key
      problems in the field of EEG, EEG forward problem and EEG inverse problem. EEG
      forward problem which aims to get the distribution of the scalp potential due to
      the known current distribution in the brain is the basis of the EEG inverse
      problem. Generally, EEG inverse problem depends on the accuracy and efficiency of
      the computational method of EEG forward problem. This paper gives a review of the
      head model and corresponding computational method about EEG forward problem
      studied in recent years.

PMID- 15143573
TI  - [Nikolai Naumovich Terebinskii (1880-1959)].

PMID- 15143575
TI  - [Surgical strategy in active infective endocarditis].
AB  - In the cardio-surgical department of the regional clinical hospital of Kirov
      oblast 117 patients (83 men and 34 women) with active infective endocarditis of
      native heart valves were operated upon: with injury of the aortal valve (61),
      mitral (37), mitral and aortal (16), tricuspidal (2), mitral, aortal and
      tricuspidal (1). During 10 days the patients were examined and prepared for
      operation which included intensive antibacterial, cardiotropic and
      immunomodulating therapy. Then the operation of prosthesing the valve, mainly
      with domestic prostheses "LIKS-2" and Karboniks-1 was performed. Lethality was
      7.6%. Recurrent endocarditis took place in 6% of cases. In reoperations
      cannulation of the femoral artery and retrograde cardioplegia were used. In
      repeated mitral prosthesing right side thoracotomy in the 4th intercostal area
      was used as the approach. The surgical strategy for active infective endocarditis
      should consist of maximally rapid examination of the patient, rapid intensive
      preparation for the operation performed in maximally early terms.

PMID- 15143574
TI  - [Surgical strategies in the diagnosis and treatment of patients with
      differentiated thyroid cancer].
AB  - Results of examination of 215 patients with differentiated thyroid cancer
      (papillary, follicular, medullary) with various degrees of involvement of
      regional lymph nodes in the process are presented. The follow-up observation
      lasted from 2 till 10 years. It was established that metastases most frequently
      affect the jugular group of nodes so it was chosen for investigation in order to
      detect the micro-metastases at the subclinic stage. Division of the surgical
      treatment into two stages (biopsy of the regional lymph nodes and
      lymphodissection within 2-3 months in case of metastases) has allowed to improve
      early results and not worsen long-term results of treatment.

PMID- 15143576
TI  - [Early results of surgical treatment of infective endocarditis].
AB  - Operations were performed on 183 patients with infective endocarditis and injury
      of the valve apparatus of the heart. Duration of the disease was from 5 weeks to
      9 years. Insufficiency of circulation of the III-IV functional class was noted in
      92% of the patients. High activity of the infective process observed in 30% of
      the patients by the moment of operation did not influence the results of surgical
      treatment. Postoperative lethality was 7.6%.

PMID- 15143577
TI  - [Bioelectrical activity of the gastrointestinal tract in acute intestinal
      obstruction].
AB  - During the period of 2001-2002 in the surgical department of the Republican
      clinical hospital there were 72 patients with acute small bowel obstruction. In
      addition to generally accepted methods of diagnosing the acute intestinal
      obstruction including general rentgenography of organs of the abdominal cavity,
      radiopaque methods, ultrasound scanning of organs of the abdominal cavity, a
      measuring-diagnostic system (polygastroenterograph "PGEG-2001") was used which
      registered and processed fluctuation of biopotentials of different parts of the
      gastrointestinal tract and measured instantaneous values of the intracavital
      gastric pressure. So, a short period of time was needed to reliably determine the
      kind and level of obstruction.

PMID- 15143578
TI  - [Methods in draining surgical procedures performed on the thoracic lymphatic duct
      in liver cirrhosis].
AB  - During the period from 1980 till 2000 212 operations were performed on the
      thoracic lymphatic duct (TLD). Different modifications of the lympho-venous
      anastomosis were used in 160 (75.4%) of them, direct external drainage of TLD in
      41 (20%) patients, ductolysis of TLD in 11 (5%) patients. In order to get lymph
      from TLD and for the following lymphosorption two kinds of operations were used:
      direct external drainage of TLD or of one of its branches and the formation of
      lymphovenous anastomosis (most frequently anastomosis of TLD with the external
      jugular vein) in combination with lymphaticostomy. A technique of chronic
      catheterization of TLD is proposed which allows performing external drainage of
      the duct for the following courses of lymphosorption in activation of cirrhosis
      without reoperations. When withdrawing the catheter from TLD the author
      recommends to make a relaxation suture tied during elimination of the drainage.
      It prevents lymphedema of the tissues and the formation of lymphatic fistulas.

PMID- 15143579
TI  - [Auto-venous femoral-popliteal bypass in patients of different age groups].
AB  - The results of autovenous femoro-popliteal shunting performed in 106 patients
      with infrainguinal atherosclerotic arterial occlusion were investigated. All the
      patients were divided into 3 groups: younger than 50, from 50 to 60 and older
      than 60 years of age. The most favorable results were registered in the group of
      patients aged from 50 to 60. In 3 years these results made up 52.2%, in 5 years-
      17.4%. The lowest indices of shunt functioning were noted in patients younger
      than 50, and 3 and 5 years later they were 38.5 and 7.7% respectively. In 70% of
      this age group patients there were injuries of the main crural arteries and
      significant changes in the phospholipid fraction level. The main cause of
      unsatisfactory results of shunting operations in the femoro-popliteal area is
      though to be the injuries of the main crural arteries and the progressing course
      of the atherosclerotic process.

PMID- 15143580
TI  - [Prophylaxis and treatment of the incompetent stump of the primary bronchus and
      tracheobronchial anastomosis with using omentoplasty].
AB  - An analysis of risk factors of incompetence of the bronchus stump or
      tracheobronchial anastomosis has shown that the statistically reliable factors (p
      < 0.05) were: male gender of the patient, neglected lung cancer, high degree of
      purulent intoxication, preoperative gamma-therapy, certain kinds of performing
      sutures, the degree of acute respiratory insufficiency. The traditional methods
      of plasty of the primary bronchus stump or tracheobronchial anastomosis in
      patients with the high objective risk of the development of incompetence of their
      sutures are known to be not effective. An experience with 70 prophylactic and
      curative omentoplasties has shown than the application of the greater omentum for
      plasty can substantially reduce frequency of the formation of acute
      bronchopleural fistulas, but the technique of fixation of the omentum to the
      trachea and opposite primary bronchus is of great significance for realization of
      the omentum plasty potential.

PMID- 15143581
TI  - [Mast cells apparatus of the duodenum in patients with gastro-intestinal
      hemorrhage of ulcer etiology].
AB  - Morphohistochemical investigations of the duodenum in patients with ulcer disease
      complicated by hemorrhage have revealed two times higher number of mast cells and
      correspondingly increased amount of histamine and heparin in the periulcerous
      area. It accounts for the focal obstacle of blood coagulation and arrest of
      hemorrhage in patients with ulcer disease.

PMID- 15143582
TI  - [Diagnosis of pre-recurrent syndrome in bleeding ulcer of the stomach and
      duodenum].
AB  - The individual surgical strategy used in the recent years has allowed to improve
      results of treatment of patients with ulcerous gastroduodenal bleedings. A
      considerable number of recurrent hemorrhages due to insufficiently reliable
      prognosis is responsible for high lethality in this pathology. An investigation
      of pathogenesis of rebleedings as well as a statistical analysis of 249 case
      histories of patients with ulcerous hemorrhages allowed detection of most
      significant clinico-laboratory and endoscopic signs of recurrent bleeding. Of the
      greatest importance were case histories of collapse, active bleeding by G.P.
      Gidikir, size of the ulcer and blood loss indices. The program Statistica 5.5
      (USA, 1998) was used for the development of the algorithm of prognosis of
      recurrent bleeding as three trees of solutions. The prognosis exactness by each
      of the trees was about 80%. The combined use of several trees substantially
      increased the prognosis reliability. The method can be recommended for wide
      practical application due to its simplicity and exactness.

PMID- 15143583
TI  - [Prospects for video-endoscopic surgical technique in incarcerated hernias].
AB  - An analysis of generalized clinical material includes 60 diagnostic laparoscopies
      performed in patients with incarcerated hernias and 48 curative endovideosurgical
      interventions in patients with incarcerated inguinal and femoral hernias.
      Attention is called to the extension of technological resources of the operative
      treatment of incarcerated hernias using the laparoscopic technique and possible
      transformations of the operative strategy in such cases.

PMID- 15143584
TI  - [On the improvement of surgical treatment of destructive pancreatitis].
AB  - Results of treatment of destructive pancreatitis during the recent 20 years have
      been analyzed. Among 189 patients with this disease there were 54.5% of women and
      45.5% of men aged from 20 to 80 years. The main principle of the surgical
      treatment was active ablation of all foci of destruction in the pancreas,
      abdominal cavity and retroperitoneal fat. "Closed", "open" and "combined"
      operations were used according to individual indications established by highly
      informative methods of diagnostics such as ultrasound, CT, retrograde
      pancreatocholangiography, laparoscopy. Combined use of the operations, flow
      lavage of bursa omentalis and retroperitoneum, complex therapy using
      intraarterial laserotherapy have allowed to reduce postoperative complications
      from 41 to 17% and mortality from 31 to 11.5%.

PMID- 15143585
TI  - [Principles of differentiated treatment of acute pancreatitis].
AB  - Results of treatment of 3372 patients with acute pancreatitis for the period from
      1990 to 2002 are analyzed. The authors have developed a medico-diagnostic
      algorithm for acute pancreatitis. The introduction of it into clinics allowed the
      general lethality from acute pancreatitis to be reduced to 2.9% for 11 years.

PMID- 15143586
TI  - [Blunt non-penetrating wounds to the chest and abdomen with non-standard injuring
      shells].
AB  - A case of a gun-shot wound with a bullet of non-lethal action is described. The
      bullet has a metallic weighting and a rubber coat. Wounds made by such bullets
      can be dangerous because of possible injuries of the vessels.

PMID- 15143587
TI  - [Clinico-morphological characteristics of injuries inflicted by shots from
      weapons of non-lethal action].
AB  - The problem of studying injuries inflicted by different kinds of self-defense
      weapons is of great interest both to medical workers of different specialties
      (experts in forensic medicine, surgeons, toxicologists etc.) and to
      criminologists. Cases from practice of clinical and forensic medicine show that
      shots from pistols PB-4 with cartridges of traumatic action depending on the
      distance and the injured area as well as on other dynamic parameters of the
      interaction of the shell and the obstacle can cause injuries of different degrees
      of severity.

PMID- 15143588
TI  - [Application of superoxide dismutase preparation for the prophylaxis of post
      traumatic broncho-pulmonary complications].
AB  - The effectiveness of endobronchial application of superoxide dismutase (SOD) for
      prevention of posttraumatic bronchopulmonary complications was analyzed in 11
      patients with severe combined traumas and dominating injuries of the chest. It
      was shown that severe combined traumas sharply initiate processes of free radical
      oxidation in tissues, intensify prooxidative activity, deplete total
      antioxidative activity and its important link--plasma and erythrocyte SOD.
      Endobronchial instillation of SOD after a severe combined trauma results in
      increased intracellular activity of catalase, total antioxidative activity, SOD,
      decreased production of lipid peroxides in homogenate of the pellet of
      bronchoalveolar lavage (BAL), reduced number of neutrophiles and higher number of
      lymphocytes in BAL pellet. Posttraumatic endobronchial instillation of SOD
      reliably improves the respiratory and metabolic function of the lungs, improves
      the surfactant system of the lungs, bronchial patency, reduces the number of
      cases of posttraumatic pneumonia.

PMID- 15143589
TI  - [Postinfectious coxarthrosis and its surgical treatment].
AB  - Results of the observation of 27 patients with postinfection coxarthrosis have
      shown expedience of using alloplasty of the hip joint with a demineralized
      osteocartilaginous transplants instead of operations of endoprosthesis in young
      patients. An original technique of alloplasty of the hip joint is proposed.

PMID- 15143590
TI  - [Current principles of correction of leg shapes in reconstructive and aesthetic
      surgery].
AB  - Main principles which should be followed when choosing the strategy of treatment
      in patients with deformities of lower extremities are describes. The authors'
      experience includes 213 patients with deformities of lower extremities, 59 of
      them were operated upon. Basing on this experience the authors have developed a
      classification allowing systematization of the methods for correction of
      deformities of legs. The following factors were taken into account: the character
      and degree of the deformity, the degree of impairment of the joint functions,
      compensatory changes, the degree of alteration of soft tissues, patient's age and
      the esthetic effect estimated by the patient.

PMID- 15143591
TI  - [Specifics of intensive therapy in abdominal gunshot wounds].
AB  - Among the wounded admitted to the departments of anesthesiology, resuscitation
      and intensive therapy there were from 57.8 to 77.6% of gunshot injuries of the
      abdomen. Successful treatment of such patients is dependent not only on the
      timeliness and quality of surgical interventions but also on the correct choice
      of intensive therapy before and during operation and in the postoperative period.
      The temporizing strategy providing for expanding the list of the methods used as
      late as the symptoms of the unfavorable course of the postoperative period can
      not be considered sufficiently effective. Complex intensive therapy with a
      forestalling action on different links of the wound disease pathogenesis in most
      cases allows not only the elimination of organic and systemic impairments
      resulting from the wound but also is more effective for defensive compensatory
      mechanisms. Differentiation of the programs of treatment depending not only on
      the severity of the patient's state but also on the character of injuries of
      organs of the abdominal and retroperitoneal areas is of the leading significance.

PMID- 15143592
TI  - [On teaching surgery at the graduation course of a medical college according to a
      new curriculum].
AB  - Teaching surgery to students of the medical college represents a complex dynamic
      process based on the achievements and advantages of domestic medical education.
      The article presents an analysis of historical aspects of teaching surgery formed
      under the influence of N.I.Pirogov's ideas and shows the necessity of searching
      for new forms of organization of teaching surgery at the up-to-date stage of
      reorganization of higher professional school. Special attention is given to a
      compulsory preservation of traditional principles of the system of teaching
      surgery verified by almost two centuries of experience of using it.

PMID- 15143593
TI  - [Feasible prognostication of coronary shunt patency after surgery of direct
      revascularization of the myocardium according to the echo-cardiological data].
AB  - The possibility to make a prognosis of patency of coronary shunts after operation
      of direct revascularization of the myocardium was investigated by the data of
      analysis of the indices of the left ventricle systolic function by findings of
      echocardiography and stress-echocardiography. Examination of 78 patients was
      carried on before and at different terms after coronary shunting. The results of
      multifactorial regression analysis show that the dynamics of rejection fraction,
      before and after operation, duration of ischemia in seconds, amount of
      nitroglycerin taken in tablets are thought to be most informative for prognosis
      of shunt patency.

PMID- 15143594
TI  - [Intraoperative ultrasonic scanning of extrahepatic bile ducts].
AB  - The intraoperative ultrasonic investigation (IOUSI) of bile tracts was used
      during laparoscopic cholecystectomy for chronic (53 patients) and acute (25
      patients) calculous cholecystitis and during 74 open operations in patients with
      mechanical jaundice. In half of the cases IOUSI was combined with intraoperative
      cholangiography (IOCG). A conclusion made on the basis of the clinical material
      suggests that IOUSI allows better assessment than IOCG of the state of the bile
      duct walls and pancreas head, the consistency of the duct content and can detect
      small (2-5 mm) concrements more exactly. However IOCG is more effective in
      determining the function of the bile tracts. So, the methods are thought to be
      not competing but mutually supplementing.

PMID- 15143596
TI  - [Prognosis of the stomach and duodenal ulcer complications: endoscopic aspects].
AB  - The visual picture of the ulcerous defect was studied in 222 patients by
      endoscopic and intraoperative methods. The prognostic assessment of the
      development of complications of ulcer disease of the stomach and duodenum is
      given on the basis of the characteristics of the ulcer process (diameter, depth,
      character of the ulcer fundus and margins).

PMID- 15143597
TI  - [On the question of functional postvagotomy complications].
AB  - The intraoperative measures preventing functional complications after vagotomy
      were determined in performing organ-saving operations on 63 patients with
      complications of ulcer disease of the duodenum. Truncal vagotomy must be
      supplemented with draining operation. The draining operations should be carried
      out with the dissection of the cicatricial-ulcerous infiltration. The
      gastroduodenal anastomosis in draining operation should be formed by a one-row
      suture. When performing selective proximal vagotomy and its variants it is
      necessary to avoid iatrogenic damage of the Laterge nerve and its terminal part-
      "crow's feet". Mobilization of the abdominal part of the esophagus during
      different variants of selective proximal vagotomy must be fulfilled along the
      length not more than 5 cm proximal to the gastro-esophageal passage and to be
      associated with a correcting operation on the esophagocardial part.

PMID- 15143595
TI  - [Patients' self assessment of postop results after reconstructive surgeries on
      the femoral-popliteal segment of the arteries and their rehabilitation].
AB  - A comparative analysis of long-term results of reconstructive operations on the
      femoro-popliteal segment performed by different techniques was based on the
      assessment of the operation results made by the patients and their social
      rehabilitation after the operation. The operations of choice may be thought to be
      reconstruction with the application of transplants of velours dacron with a
      gelatin impregnation (VDGI), polytetraftoroethylene (PTFE) and autovein.
      Transplants of VDGI are found to be preferable. The long-term results of using
      PTFE transplants in the femoro-popliteal position were shown by the authors to be
      inferior to VDGI transplants. Since PTFE is much more expensive than dacron, the
      practice of so wide using this material should be revised. The authors believe
      that endarterectomy can not be considered to be the operation of choice for long
      standing occlusions of the superficial femoral artery. They should be used but
      for critical ischemia of the extremity when trying to safe it if the transplants
      of VDGI and PTFE and good autovein are not available. The long-term results of
      using lavsan-ftorolon transplants in the femoro-popliteal position suggest that
      they should not be used in practice.

PMID- 15143598
TI  - [Leiomyoma of the small intestine complicated by bleeding].

PMID- 15143599
TI  - [Concurrent micro-cellular cancer of the lung and atypical carcinoid of the
      vermiform process].

PMID- 15143600
TI  - [Criteria of assessment of restriction of vital activity of patients after total
      endoprosthesis of the hip joint].
AB  - Total endoprosthesis of the hip joint is an effective method of rehabilitation of
      patients with a severe pathology of the hip joint. But the lack of exact criteria
      of assessment of restriction of vital activity of patients after total
      endoprosthesis results in leveling the effects of medical rehabilitation due to
      the existing stereotype solution of the MSE bureau and so the majority of
      patients (90%) after operation get invalidization of the I and II groups for a
      long time without sufficient causes. Results of complex clinico-rentgenological,
      biomechanical, electrophysiological examinations and expert assessment of 450
      patients after implantation of various domestic and foreign endoprostheses
      allowed the elaboration of differentiated criteria for the examination of
      restricted viral activity depending on the nosological form of the disease,
      degree of the disturbance of the statico-dynamic function, prognosis,
      complications, character and conditions of work.

PMID- 15143601
TI  - [On a unified approach to nomenclature of sequelae from compression injuries and
      acute impairment of main blood circulation].
AB  - Different compression traumas and various acute disturbances of the main blood
      circulation, chiefly of extremities, result in similar ischemic and reperfusion
      lesions leading to the development of life-threatening endotoxicosis. In the
      literature there are diverse interpretations of these phenomena. These notions
      are not similar in medical Encyclopedia either. The authors consider that its
      pathogenetical essence must be called "postischemic endotoxicosis" or as an
      alternative "a reperfusion syndrome". For such interpretations to be complete in
      different clinical situations, it is necessary to mention the specific (or
      similar but different) causes of ischemia and its localization, and in such a
      diversity they can not have a common designation. So the interpretation of this
      pathology in such cases should consist of two parts--a pathogenetical basis
      common for all, and a diverse etiological characteristic.

PMID- 15143603
TI  - [Combined injuries of arteries, nerves and tendons of the forearm].
AB  - Combined injuries of the forearm occupy an important place in modern structure of
      functionally severe traumas. Discussions concerning the best time for nerve
      reconstructions and unsolved questions of a necessity to restore one of the
      arteries if the other is safe confirms the importance of the problem. An analysis
      of the domestic and foreign literature data on diagnosing and treatment of the
      traumas in question is given. Main specific features of treatment depending on
      the time, character of injuries and functional role of the injured structures are
      described.

PMID- 15143602
TI  - [On 100th anniversary of A. A. Kuliabko's experiments on heart resuscitation].

PMID- 15143604
TI  - [ Randomized studies].

PMID- 15143606
TI  - [Neoadjuvant radiochemotherapy in the treatment of esophageal squamous
      carcinoma:Preliminary results in a series of 15 patients].
AB  - The purpose of this study is to analyze the experience of the Center of General
      Surgery and Liver Transplantation from Fundeni Clinical Institute (Bucharest)
      regarding the results of neoadjuvant radiochemotherapy in the squamous carcinoma
      of the esophagus. During 01.01.2001-09.07.2003, 15 patients with squamous
      carcinoma of the esophagus were treated using neoadjuvant radiochemotherapy
      (RCT); 13 patients (86%) underwent esophageal resection (in 2 patients resection
      was not possible due to the mediastinal invasion). Complete histological response
      (the lack of malignant tissue on the esophagectomy specimens) was noted in 5
      cases. The morbidity and mortality rates were 48%, respectively 6%. RCT increases
      the resectability in esophageal cancer and decreases the postoperative morbidity
      and mortality.

PMID- 15143605
TI  - [Preoperative modern evaluation of patient with esophageal stenosis].
AB  - It is well known the difficulty of a precise evaluation in the pretherapeutic
      stage of any esophageal pathology, especially that of obstructive lesions.
      Preoperatory information should be as accurate as possible, any evaluation error
      leading to surgical manoeuvres that can later be regretted. From the current
      practice one can easily observe that there is no typical exploratory protocol,
      each having its own specific limits, high costs that are not negligible, and some
      of them are not always immediately available. It is obvious that para-clinic
      approach has changed, due to technological progress that has increased the
      accuracy of medical information, but has also increased costs. The standard
      protocol has lead to a retrospective analysis of the esophageal obstruction cases
      that were hospitalized in the Sf Maria Clinic of Surgery, during 1981-2002,
      regarding diagnostic algorythm and treatment used.

PMID- 15143607
TI  - [Organic hypoglycemia of pancreatic cause].
AB  - Insulinomas represent the most common cause of organic hypoglycemia. They are
      rare tumors: a review of the world literature reported a total number of 2000
      3000 cases. The clinical diagnosis is based on the Whipple triad, which consists
      of: a) symptoms of hypoglycemia, b) blood glucose level: 40-50 mg/dl during the
      crisis, c) relief of symptoms after oral or intravenous administration of
      glucose. The most ticklish problem is the settlement of the accurate location of
      the tumor. Nowadays, there are many diagnostic methods; one of the best appears
      to be intra-operative ultrasonography. The authors analyse a series of 16
      patients, operated between 1985 and 2002 in "I. Juvara" Surgical Clinic and
      present their opinions concerning tactic and technical aspects of different
      surgical procedures, with their advantages and limits. The results of the
      surgical treatment are detailed. There are also mentioned new imagery techniques
      and laparoscopic procedures, from recent medical issues.

PMID- 15143609
TI  - [Diagnosis characteristics features in breast cancer].
AB  - Representing about 20% of all woman's cancers in all the world, breast cancer is
      a multifactorial disease with unknown mechanism facts which may explain the
      significant growth of incidence and mortality in the last few years. In the
      absence of screening program in majority cases the diagnosis is discovered too
      late. In this present study we have made a retrospective study on 487 patients
      during 1996-2000 at the 1st Surgical Clinic from Craiova. The purpose of this
      study was the defining of the population with an increased risk which has to be
      monitorized. In order to accomplish it, we have carefully supervised some of
      clinical parameters: sex, age, social environment, physiological and pathological
      antecedents, heredocolateral antecedents, and the constitutional type. The study
      method was the comparative analysis, and the evaluation according to the modern
      statistical methods. The risk factors, which can be surely used in defining the
      groups of population with an increased risk, which should be supervised for an
      active discover of breast cancer, as the resulted from our study, are: the age
      decades V, VI, and VII with maximum incidence in subgroups 45-49 and 60-64 years
      old; early monarch (67.15%); delayed menopause, over 50 years old (84.4%); long
      exposure to sexual hormones during the reproductive period (the period of
      menstrual cyclicity over 32 years old); the pathology of the benign tumor, the
      biggest risk belonging to the proliferative tumours (intraductal papiloma);
      hyperestrogenism. The only improving method of the therapeutical results in
      breast cancer is an early discover of it, which can be accomplished only by the
      implementation of a national program of active discover, in which the essential
      part belongs to the primary care helped by a widely-broadcast medical education.

PMID- 15143608
TI  - [Use of prosthesis in inguinal hernia repair].
AB  - AIMS: To evaluate the use of mesh in the evolution of hernia repair technique
      during a period of twelve years. PATIENTS--METHODS: From january 1991, to
      december 2002, 1306 patients 1136 men, 190 women, with inguinal hernia, with a
      mean age of 47.4 years old (15-98) have had an elective surgical repair. 1097
      (83.9 per cent) were unilateral. 209 (16.1 per cent) were recurrent hernia.
      Clinical data, operative technique have been prospectively evaluated: Four
      techniques were used: Shouldice procedure, Stoppa operation and laparoscopic
      repair (TEP) in 1992 and Lichtenstein technique since 1993. RESULTS: During the
      study, meshes were used in 65.7 per cent of the patients respectively 33.3 per
      cent for Lichtenstein, 26.9 per cent for laparoscopic repair and only 5.3 per
      cent for Stoppa open procedure. During the study, prosthesis rate increased from
      9.1 to 85.4 per cent for primary hernia and from 10 to 100 per cent for recurrent
      hernias. To day, Stoppa procedure is not yet performed. Herniorraphies decrease
      from 91.9 to 14.6 per cent. CONCLUSIONS: "Tension free" techniques represent 85.4
      per cent of all procedures at the end of the study, specially Lichtenstein
      operation (65 per cent) which seems to become the new "Gold Standart" in inguinal
      hernia repair.

PMID- 15143611
TI  - [Incisional hernia repair using full-thickness intraperitoneal mesh].
AB  - Prosthetic materials proved to be a real success for incisional hernia repair,
      still there is a strong debate regarding the best mesh and procedure to be used.
      Most surgeons avoid full-thickness replacement with intraperitoneal mesh because,
      occasionally, an intense inflammatory response may lead to severe adhesions or
      enterocutaneous fistula. Still, interposition of the omentum between the
      abdominal contents and the mesh is a safe and natural method of visceral
      protection. Since July 1998, we used this technique in 33 cases treated for
      antero-lateral abdominal defects, operations that were followed by only 15% early
      and 3% late complications. Monofilament polypropylene meshes (Bard, Davol Inc.)
      were used in most cases. Although our results need further evaluation, may be
      considered favourable on short and medium term comparing to Romanian experience,
      which is based mainly on extraperitoneal placement of the mesh. The study is a
      good opportunity to review the literature regarding this issue.

PMID- 15143610
TI  - [Alloplastic or autoplastic in incisional hernia].
AB  - The study is retrospective and includes 194 patients with incisional hernia (IH).
      Local and general factors involved in IH pathogeny were tried to be identified,
      namely tactical and technical solutions for surgically solving the abdominal
      parietal deficiencies. Main risk factors, for the lot having been studied, are
      general: obesity, diabetes, cancer and local: wound suppuration, repeated
      surgical operations, emergency surgery, multiparity and physical effort. Simple
      suture and aloplastic procedures prevailed being adapted to the type of lesion,
      intraoperatory identified. For patients with multiple orifices different
      techniques were used during the same surgical operation.

PMID- 15143612
TI  - [Intraoperative diagnosis of common biliary duct using laparoscopic
      ultrasonography].
AB  - THE AIM: Of the study is to show the advantages and limits of laparoscopic
      echography in exploration and diagnosis of common biliary duct lithiasis, as it
      is evidenciated in the experience of our surgical department. MATERIAL AND
      METHODS: Between 31.03.1997-31.12.2002 we have made 878 laparoscopic
      interventions to patients with hepatho-biliary pathology. We made a prospective
      study and performed 116 laparoscopic ultrasonography examinations for exploration
      of the liver and bile ducts. We used an Aloka SSD 2000 device with a linear
      laparoscopic flexible transductor. RESULTS: We obtained a very good visualization
      in 97 cases (83.6%) and medium visualization in 19 cases (16.4%). The medium time
      of the examination was 10 minutes (variations between 5-20 minutes). We
      discovered pathological modifications in principal bile duct and cystic using
      color Doppler examination in acute and chronic inflammatory lesions with
      important anatomical modifications. CONCLUSIONS: 1. laparoscopic ultrasonography
      it is an ideal technique in common bile duct lithiasis diagnosis, with 90-98%
      precision. 2. intraoperative ultrasonography does not need preliminary dissection
      of cystic and offers the possibility of exploration of the liver and pancreas. 3.
      it needs a learning curve and collaboration between surgeon and ultrasonography
      specialist.

PMID- 15143613
TI  - [Functional secondary megaduodenum].
AB  - This paper aim is to present the case of a 72 year old male, diagnosed with
      functional secondary megaduodenum. We intend to discuss the pathogenic and
      positive diagnostic difficulties (the presence or absence of a mechanical
      obstructive factor or the participated of the megaduodenum in an intestinal
      pseudo-obstruction syndrome). Also we outline the rare frequency of this disease
      and especially the therapeutic difficulties: inefficiency of conservatory
      treatment, delicate problems of surgical tactics and technique.

PMID- 15143614
TI  - [Completion gastrectomy associated with pancreaticoduodenectomy].
AB  - The authors present the case of a male patient, aged 56, operated (partial
      gastrectomy) for peptic ulcer 20 years ago, who is admitted for epigastric pain
      and distension, frequent vomiting, asthenia and weight loss. Physical
      examination, barium meal and upper digestive endoscopy with biopsy established
      the diagnosis of carcinoma of the gastric stump, due to malignant transformation
      of adenomatous polyps, with duodenal invasion. Completion of gastrectomy and
      pancreaticoduodenectomy was performed, with good postoperative results. Although
      the extent of resection may appear excessive, our attitude was justified by the
      features of the lesion and good biological condition of the patient.

PMID- 15143616
TI  - [Laparoscopic subtotal splenectomy in the treatment of hereditary spherocytosis].
AB  - Clinical manifestations of hereditary spherocytosis, the most common red blood
      cell membrane disorder, can be controlled by splenectomy. However, concerns
      regarding exposure of patients to a life long risk for overwhelming infections
      have restricted its use, especially in children. Subtotal splenectomy, as long as
      80% to 90% of the enlarged spleen is removed, is a logical alternative. Subtotal
      splenectomy was effective in decreasing the hemolytic rate, while maintaining the
      phagocytic and immune function of the spleen. This surgical procedure should be
      considered in transfusion-dependent infants and children whit hereditary
      spherocytosis and in older patients whit erythrocyte membrane defects. Based on
      our experience in laparoscopy (120 laparoscopic splenectomies) and open subtotal
      splenectomy (5 cases) we performed 2 laparoscopic subtotal splenectomies in
      patients with hereditary microspherocytosis with good short term results. We have
      had no problem with blood loss and no transfusions were needed. The procedure can
      be performed safely and easily with all the traditional advantages of a minimally
      invasive approach. In order to evaluate the long term clinical benefit a minimal
      follow-up of 5 years is needed.

PMID- 15143615
TI  - [One case of multiple abdominal hydatidosis].
AB  - It is presented the case of a 45 years old female patient transferred in our
      clinic from Parasitology Clinic with the diagnosis of hepato-splenic hydatidosis.
      Preoperative echography presented 3 abdominal hydatid cysts (hepatic, splenic and
      free in the peritoneal cavity--greater omentum). Intraoperative exam confirmed
      the preoperative evaluation. The operation consisted in two ideal cystectomies
      associated with one partial cystectomy with evacuation and drainage.
      Postoperative evolution was simple.

PMID- 15143617
TI  - [Subfascial endoscopic perforating veins section].
AB  - AIM: Subfascial endoscopic perforating veins section (SEPS) is a modern surgical
      method used in the treatment of chronic venous insufficiency. The paper presents
      the postoperative results using SEPS technique at the patients with chronic
      venous insufficiency of the inferior limbs of different etiologies. MATERIAL AND
      METHOD: We followed 26 patients, 16 women and 10 men, with ages between 16-75
      years, with chronic venous insufficiency at the inferior legs. 20 patients had
      only one inferior limb affected by the disease and 6 patients had both limbs
      involved. They were, after CEAP clinical criterion, in C4, C5 and C6 classes and
      they had three different etiologies as primary varices with an evolutive period
      of 20 years, postthrombotic syndrome and congenital varices. We performed 32 SEPS
      operations in the 1-rst Clinic of Surgery, University of Medicine and Pharmacy
      "Victor Babes" Timisoara. RESULTS: The time of healing and postoperative
      complications were reduced after SEPS procedures. The healing is 100% at three
      months after surgery. The check up after 12 months showed a rate of 87.5% of
      healing. We recorded 4 unilateral relapses at patients that had postthrombotic
      syndrome. DISCUSSIONS: The study realized in our clinic comparing with other
      studies from the literature, shows that our results are similar to that recorded
      in medical centers from other countries demonstrating the superiority of SEPS
      methods comparing with the classical Linton or Felder methods of perforating
      veins ligation.

PMID- 15143618
TI  - [The surgical treatment of the parastomal hernia using prolene mesh].
AB  - Parastomal herniation is a frequent complication in enterostomy. The therapeutic
      strategy consists in three approaches: local fascial repair, relocation of the
      stoma, local repair of the parietal defect using nonabsorbable meshes. In our
      clinic between 1997-2002 we used monofilament meshes placed in sublay position at
      four patients with parastomal herniation. At three patients we used midline
      laparotomy placing the mesh round the colostomy on preperitoneal space, after
      preparing the hernia sack. The size of the mesh goes beyond the parastomal
      parietal defect with 3-5 cm. At the fourth patient we placed the mesh round the
      preperitoneal segment of the colon using a combined intraperitoneal and
      parastomal procedure, the size of the mesh going beyond parastomal parietal
      defect in this case too with 3-5 cm. The immediately and delayed results was
      favorable. CONCLUSIONS: The parastomal herniation's surgical repair applying
      prolen mesh can be a therapeutic alternative with good results.

PMID- 15143619
TI  - Influence of mental motor imagery on the execution of a finger-to-thumb
      opposition task.
AB  - The present fMRI study compares regional distribution of the cortical activity
      during the execution of unilateral hand movements (finger-to-thumb opposition)
      preceded or not by their motor simulation (S + E and E condition, respectively).
      The results show that, overall, the number and the spatial distribution of
      activated voxels are both increased in the S + E with respect to the E condition.
      The motor performance preceded by mental rehearsal is related to selective
      increase of the cortical activity. Among the motor areas that are found active
      during the simple motor execution a significant enhancement of functional
      activation during the S + E condition ipsilateral primary motor regions (M1). The
      activity increase may be accounted by a sort of neural recruiting that is made
      possible by the overlapping of cortical networks involved in both motor output
      and motor imagery. The beneficial effects of "mental practice" on the physical
      performance may rely to the close temporal association between motor rehearsal
      and actual performance.

PMID- 15143620
TI  - Blockage of vibrissae afferents: I. Motor effects.
AB  - In the past, it has been proposed that the rat vibrissae play an important role
      in other hand, postural abnormalities, muscle tone decreases and hypomotility
      after sensory organ destructions were proposed as evidence supporting the "level
      setting" or "tonic" hypothesis. This hypothesis postulates that afferent
      activity, besides its well know transductive functions, sets the excitability
      state of the central nervous system. We thought the vibrissal system to be a good
      model to dissect these two postulated roles because vibrissae trimming would
      annul the transductive function without affecting the integrity of nerve
      activity. Thus we compare the effects of trimming the whiskers with blocking the
      vibrissal afferent nerves on two types of motor behavior: activity in an open
      field and walking over a rope connecting two elevated platforms. We found that
      only vibrissal afferent blockage (both nerve section and local anaesthesia)
      produced severe failures in the motor performances studied. These effects could
      not be fully explained by the abolition of the vibrissae as a sensory modality
      because cutting the whiskers did not significantly affect the motor performance.
      These data are discussed in reference to a tonic or general excitatory function
      of sensory inputs upon the central nervous system.

PMID- 15143622
TI  - Blockage of vibrissal afferents: III. Electrocorticographic effects.
AB  - We have shown signs of behavioral depression after vibrissal deafferentation.
      Locomotor slowing, motor impairments and footshock thresholds increment were
      demonstrated after vibrissal afferent blockages. Here, we study the
      electrocortical (ECoG) effects of vibrissal pad anaesthesia, also replicated by
      bilateral brachial plexus blockage. We found in both cases, that this acute and
      massive deafferentation produces synchronization over the entire neocortex
      accompanied by an important loss of muscular electrical activity. Slow waves
      observed in this condition were similar to those recorded in the sleeping rat
      without any treatment, but in our case, there were no behavioral signs of sleep.
      Thus a clear behavioral electroencephalographic dissociation was obtained by
      acute deafferentation. These results would seem to support the sleep
      deafferentation hypothesis.

PMID- 15143621
TI  - Blockage of vibrissae afferents: II. Footshock threshold increments.
AB  - Because of their dense innervation rat vibrissae have been regarded as a very
      important sensory system. Many behavioral deficits have been reported by other
      authors after rat vibrissal afferent blockades. In the present work we found
      significant threshold increments to footshock following either reversible nerve
      block (procaine or nerve pressure) or section of the vibrissal afferent nerves,
      but not following vibrissae trimming. These results are discussed in reference to
      the tonic or level-setting function of afferent systems.

PMID- 15143623
TI  - Convergence of forelimb afferent actions on C7-Th1 propriospinal neurones
      bilaterally projecting to sacral segments of the cat spinal cord.
AB  - Propriospinal neurones located in the cervical enlargement and projecting
      bilaterally to sacral segments of the spinal cord were investigated
      electrophysiologically in eleven deeply anaesthetized cats. Excitatory or
      inhibitory postsynaptic potentials from forelimb afferents were recorded
      following stimulation of deep radial (DR), superficial radial (SR), median (Med)
      and ulnar (Uln) nerves. 26 cells were recorded from C7, 22 from C8 and 3 from Th1
      segments. The majority of the cells were located in the Rexed's laminae VIII and
      the medial part of the lamina VII. In 10 cases no afferent input from the
      forelimb afferents was found. In the remaining neurones effects were evoked
      mostly from DR (88%) and Med (63%), less often from SR (46%) and Uln (46%).
      Inhibitory actions were more frequent than excitatory. The highest number of
      IPSPs was evoked from high threshold flexor reflex afferents (FRA)--all
      connections were polysynaptic. However, inhibitory actions were often evoked from
      group I or II muscle afferents (polysynaptic or disynaptic) and, less frequently,
      from cutaneous afferents (mostly polysynaptic). Di- or polysynaptic IPSPs often
      accompanied monosynaptic EPSPs from group I or II muscle afferents. Disynaptic or
      polysynaptic EPSPs from muscle and cutaneous afferents were also recorded in many
      neurones, while polysynaptic EPSPs from FRA were observed only exceptionally.
      Various patterns of convergence in individual neuronal subpopulations indicate
      that they integrate different types of the afferent input from various muscle and
      cutaneous receptors of the distal forelimb. They transmit this information to
      motor centers controlling hind limb muscles, forming a part of the system
      contributing to the process of coordination of movements of fore--and hind-
      limbs.

PMID- 15143624
TI  - Spontaneous K-complexes in behaving rats.
AB  - The K-complex (KC) is an electrographic rhythmic pattern present in human and cat
      sleep EEG. In long-term multisite videoEEG recordings in behaving Sprague-Dawley
      (SD) rats, well-defined spontaneous KCs were observed during sleep. Sprague
      Dawley rats were implanted with multiple electrodes bilaterally along the antero
      posterior axes at the locations F1, F2, F7, F8, T3, T4, P3, P4, all against a
      ground reference placed in the midline above the cerebellum. Multiple, closely
      spaced cortical electrodes allowed two-dimensional surface brain mapping of the
      power spectra distribution. Two silver wires were also inserted into nuchal
      muscles to record EMG activity. Each rat was monopolarly recorded from 0900 h to
      1500 h in a natural dark-light rodents, we examined the patterns of appearance in
      various conditions, the progression through a full sleep-waking cycle, the shape,
      density, spectral components, and spatial distribution in power spectra. The rat
      KC appears to share similar features with the human and cat KC.

PMID- 15143626
TI  - Numerical study of light correlations in a random medium close to the Anderson
      localization threshold.
AB  - We applied a finite-difference time domain algorithm to the study of field and
      intensity correlations in random media. Close to the onset of Anderson
      localization, we observe deviations of the correlation functions, in both shape
      and magnitude, from those predicted by the diffusion theory. Physical
      implications of the observed phenomena are discussed.

PMID- 15143628
TI  - Fast wavelength-parallel polarimeter for broadband optical networks.
AB  - We describe a novel wavelength-parallel polarimeter operating in the light-wave
      band that measures the complete state of polarization of 256 wavelengths in
      parallel within 20 ms (software-limited), with the potential for submillisecond
      operation. By use of fast switching ferroelectric liquid crystals in conjunction
      with an InGaAs arrayed detector, selection and wavelength-parallel detection of
      individual polarization components can be achieved within approximately 150
      microseconds. This instrument offers unprecedented sensing capability that is
      relevant to the compensation of polarization-related impairments in high-speed
      light-wave communications.

PMID- 15143627
TI  - Light spectra in the near field of random media.
AB  - The spectrum of light in close proximity to a highly scattering, randomly
      inhomogeneous medium is investigated. We find differences between the far- and
      near-field spectra that are due to evanescent wave contributions. We show that
      these spectral modifications depend on the coherence properties of an equivalent
      planar source, which, in turn, relates to the statistical characteristics of the
      interface.

PMID- 15143625
TI  - Increased calbindin-D28K immunoreactivity in rat cerebellar Purkinje cell with
      excitatory amino acids agonists is not dependent on protein synthesis.
AB  - The calcium binding protein Calbindin-D28K (CaBP) is abundantly expressed in
      cerebellar Purkinje cells and show increased immunoreactivity (CaBP-IR) when
      challenged with glutamate or an analog agonist for the ionotropic glutamate
      receptor (iGluR). Here we report that t-ACPD, a metabotropic glutamate receptor
      (mGluR) agonist, produced small increases in CaBP-IR which was potentiated by a
      mGluR antagonist The increase in CaBPIR was not due to de novo protein synthesis
      because the translational inhibitors (cycloheximide and emetine) or
      transciptional inhibitors (actinomycine-D and a-amanitine), did not prevent the
      EAA enhanced CaBP-IR. The CaBP-IR in the PC appears to be coupled to the
      ionotropic rather than the metabotropic glutamate receptors, but the latter
      become effective in the presence of their blocker, L-AP3. The results suggest
      that CaBP may increase its IR through a conformational change of the protein
      itself.

PMID- 15143629
TI  - Experimental observation of autosoliton propagation in a dispersion-managed
      system guided by nonlinear optical loop mirrors.
AB  - Observation of autosoliton propagation in a dispersion-managed optical
      transmission system controlled by in-line nonlinear fiber loop switches is
      reported for what is believed to be the first time. The system is based on a
      strong dispersion map with large amplifier spacing. Operation at transmission
      rates of 10 and 40 Gbits/s is demonstrated.

PMID- 15143630
TI  - Chaotic ray dynamics in an optical cavity with a beam splitter.
AB  - We investigate the ray dynamics in an optical cavity when a ray-splitting
      mechanism is present. The cavity is a conventional two-mirror stable resonator,
      and the ray splitting is achieved by inserting an optical beam splitter
      perpendicular to the cavity axis. Using Hamiltonian optics, we show that such a
      simple device presents surprisingly rich chaotic ray dynamics.

PMID- 15143631
TI  - Simple expressions for performance parameters of complex filters, with
      applications to super-Gaussian phase filters.
AB  - To study the three-dimensional (3-D) behavior produced by complex filters, we
      have extended the expressions for the axial and the transverse gain to the case
      in which the best image plane is not near the paraxial focus. Super-Gaussian
      phase filters are proposed to control the 3-D image response of an optical
      system. Super-Gaussian phase filters depend on several parameters that modify the
      shape of the phase filter, producing tunable control of the 3-D response of the
      optical system. The filters are capable of producing a wide range of optical
      effects: transverse superresolution with high depth of focus, 3-D
      superresolution, and transverse apodization with different axial responses.

PMID- 15143632
TI  - Superresolution in compensated telescopes.
AB  - We present a procedure for attaining resolution beyond the diffraction limit in
      ground-based telescopes. This procedure is based on the use of rotationally
      symmetric pupil plane filters that can be easily implemented in dynamic optical
      devices such as a deformable mirror of an adaptive-optics system. We show that a
      successful application of the technique requires partial compensation for
      atmospheric distortion by adaptive optics. Consequently, we derive the required
      level of compensation as a function of the atmospheric conditions. Finally, our
      results are checked using simulated data.

PMID- 15143633
TI  - Correct interpretation of spectral interference measurements of weakly absorbing
      films of micrometer thickness.
AB  - We present analytical equations based on thin-film optics with which to extract
      the thickness of weakly absorbing films from spectral interference measurements,
      using only the observed constant interference frequency. It is shown that the
      assumption of a constant index of refraction n for the analysis of interference
      frequency omega 0 introduces significant errors into the thickness calculation.
      Instead, the first derivative of n with respect to the energy, n', has to be
      included as well to yield the correct film thickness, even for small values of
      n'. The equations presented can be used as constraints in appropriate numerical
      methods to improve the film thickness iteratively.

PMID- 15143634
TI  - Magneto-optical nonreciprocal phase shift in garnet/silicon-on-insulator
      waveguides.
AB  - We demonstrate the integration of a single-crystal magneto-optical film onto thin
      silicon-on-insulator (SOI) waveguides by use of direct wafer bonding. Simulations
      show that the high confinement and asymmetric structure of SOI allows an
      enhancement of approximately 3x over the nonreciprocal phase shift achieved in
      previous designs; this value is confirmed by our measurements. Our structure will
      allow compact magneto-optical nonreciprocal devices, such as isolators,
      integrated on a silicon waveguiding platform.

PMID- 15143635
TI  - Frequency comb linewidth of an actively mode-locked fiber laser.
AB  - We report what is to our knowledge the first measurement of the linewidth of the
      frequency comb lines of a mode-locked Er-doped fiber laser. By propagating the
      output pulses through fiber as long as 1000 km in a modified self-heterodyne
      arrangement, we have measured the effective linewidth of the comb lines to be
      less than 12 kHz on a 5-ms time scale; the width is due primarily to frequency
      jitter from environmental fluctuations. Deconvolution of the spectral line shapes
      by use of Voigt analysis yields an upper limit of the intrinsic Lorentzian width
      of 3 kHz.

PMID- 15143636
TI  - Single-mode direct-ultraviolet-written channel waveguide laser in neodymium-doped
      silica on silicon.
AB  - A waveguide laser with a neodymium-doped silica core is fabricated on a silicon
      substrate by a combination of flame hydrolysis deposition, solution doping, and
      direct UV writing. The neodymium-ion concentration is estimated to be
      approximately 8000 parts in 10(5). The propagation loss around 1.05 microns is <
      0.8 dB/cm. Lasing in the range 1048-1056 nm and 1356 +/- 1 nm is observed. A
      slope efficiency of 33% for a high-reflectivity output coupler and a threshold of
      4 mW of absorbed power for a 25% output coupler are measured for the 4F3/2-
      >4I11/2 transition.

PMID- 15143637
TI  - Spinning-disk self-referencing interferometry of antigen-antibody recognition.
AB  - A gold ridge microstructure fabricated to a height of lambda/8 on a high
      reflectivity substrate behaves as a wave-front-splitting self-referencing
      interferometer in phase quadrature when illuminated by a Gaussian laser beam and
      observed in the far field along the optic axis. When immuno-gammaglobulin (IgG)
      antibodies are selectively immobilized on the gold microstructure, they recognize
      and bind to a specific antigen, which shifts the relative optical phase of the
      interferometer and modifies the far-field diffracted intensity. We detect bound
      antigen interferometrically on spinning disks at a sampling rate of 100 kHz and
      verify the interferometric nature of the signal by using two quadratures of
      opposite sign to rule out effects of dynamic light scattering. Strong molecular
      recognition is demonstrated by the absence of binding to nontarget molecules but
      strong signal change in response to a specific antigen. This BioCD has the
      potential to be applied as a spinning-disk interferometric immunoassay and
      biosensor.

PMID- 15143639
TI  - NOISE 2 imaging system: seeing through scattering tissue with a reference point.
AB  - We propose a fly-eye-like imaging system for seeing objects embedded in
      scattering media. Objects are recovered from many speckled images observed by a
      digital camera through a microlens array. Each microlens in the array generates a
      speckle image of the object buried between two layers of chicken breast tissue.
      In the computer each image is Fourier transformed jointly with an image of the
      speckled pointlike source captured under the same conditions. A set of the
      squared magnitudes of the Fourier-transformed pictures is accumulated to form a
      single average picture. This final picture is again Fourier transformed,
      resulting in the reconstruction of the hidden object.

PMID- 15143640
TI  - Radiance-based monitoring of the extent of tissue coagulation during laser
      interstitial thermal therapy.
AB  - Optical monitoring relates the dynamic changes in measured light intensity to the
      extent of treatment-induced coagulation that occurs during laser interstitial
      thermal therapy. We utilized a two-region Monte Carlo simulation to elucidate the
      nature of the changes in interstitial radiance and fluence that result from the
      formation of a volume of thermal coagulation surrounding a cylindrical emitter.
      Using simulation results, we demonstrate that radiance sensors are more sensitive
      than traditional fluence sensors to coagulation-induced scattering changes.
      Radiance measurements take advantage of directional detection angles that are
      more receptive to the onset and passing of the coagulation boundary. We performed
      experiments with albumen phantoms to demonstrate the practicality of the radiance
      method for monitoring interstitial laser thermal therapy.

PMID- 15143641
TI  - Influence of laser polarization on ocular refractive parameters after refractive
      surgery.
AB  - We provide an adjustment factor for ablation algorithms used in photorefractive
      laser surgery that takes into account how laser polarization in reflection losses
      affects the cornea. We evaluate the influence of this factor on corneal radius
      and asphericity after surgery, showing that it is significant for visual
      performance (effective visual acuity is reduced) and for the correction of eye
      aberrations. Our data indicate that this adjustment factor should be included in
      the ablation algorithms (depending on the polarization state of each laser
      device) that are proposed for customized corneal ablation, which need great
      accuracy for minimization of eye aberrations.

PMID- 15143642
TI  - Effect of pigment packaging on diffuse reflectance spectroscopy of samples
      containing red blood cells.
AB  - We present the results of diffuse reflectance measurements made on the surface of
      a tissue-simulating phantom containing intact human erythrocytes. These
      measurements indicate that the absorption spectrum of hemoglobin in its natural
      environment is significantly different from that measured in homogeneous fluid
      solution, especially in the spectral regions of highest absorption. We show that
      this difference can be explained by the pigment packaging theory developed by
      Duysens [Biochim. Biophys. Acta 19, 1 (1956)] and that the adoption of basis
      spectra that take this effect into account improves the accuracy of fitting
      diffuse reflectance spectra.

PMID- 15143645
TI  - One-mode model for patterned metal layers inside integrated color pixels.
AB  - Optimized design of the optical filters inside integrated color pixels (ICPs) for
      complementary metal-oxide semiconductor image sensors requires analytical models.
      ICP optical filters consist of subwavelength patterned metal layers. We show that
      a one-mode model, in which subwavelength gaps in the metal layer are described in
      terms of single-mode waveguides, suffices to predict the salient features of
      measured ICP wavelength selectivity. The Airy-like transmittance formula, derived
      for transverse-electric polarization, predicts an angle-independent cutoff
      wavelength, which is in good agreement with predictions made with a two
      dimensional finite-difference time-domain method.

PMID- 15143643
TI  - Directional imaging of the retinal cone mosaic.
AB  - We describe a near-IR scanning laser ophthalmoscope that allows the retinal cone
      mosaic to be imaged in the human eye in vivo without the use of wave-front
      correction techniques. The method takes advantage of the highly directional
      quality of cone photoreceptors that permits efficient coupling of light to
      individual cones and subsequent detection of most directional components of the
      backscattered light produced by the light-guiding effect of the cones. We discuss
      details of the system and describe cone-mosaic images obtained under different
      conditions.

PMID- 15143644
TI  - Multiple-discriminant analysis for light-scattering spectroscopy and imaging of
      two-layered tissue phantoms.
AB  - We propose a new method for enhancing the sensitivity of the reflectance spectrum
      to the scattering feature of the superficial tissue layer. This method is based
      on multiple-discriminant analysis in the eigensubspace of the spectrum.
      Considering the application of scattering imaging, we evaluated this method by
      performing multispectral imaging of two-layered tissue phantoms. A color map
      converted from the spectral reflectance corresponds well to variations in the
      size of the scattering in the first layer.

PMID- 15143646
TI  - Vacuum-ultraviolet beam array generation by flat micro-optical structures.
AB  - Micro-optical structures for VUV laser beam shaping and wave-front sensing were
      manufactured by thin-film deposition onto CaF2 and transfer by etching. Arrays of
      Bessel-like F2 laser beams at a wavelength of 157 nm with extremely small conical
      angles were generated by microaxicon lenses. Beam propagation was studied in
      simulations and experiments. Apodization by absorbing layers is proposed for beam
      cleaning.

PMID- 15143638
TI  - Enhanced second-harmonic generation by means of high-power confinement in a
      photovoltaic soliton-induced waveguide.
AB  - We present the first experimental demonstration of enhanced second-harmonic
      generation (SHG) by means of power confinement with a femtosecond laser in a
      photovoltaic soliton-induced waveguide. A dark spatial soliton created with a
      weak cw laser beam in a photovoltaic lithium niobate crystal induces an efficient
      waveguide for SHG, leading to a 60% enhancement of the conversion efficiency.

PMID- 15143647
TI  - Performance of a phase-conjugate engine implementing a finite-bit phase
      correction.
AB  - The achievable Strehl ratio when a finite-bit correction to an aberrated wave
      front is implemented is examined. The phase-conjugate engine used to measure the
      aberrated wave front consists of a quadrature interferometric wave-front sensor,
      a liquid-crystal spatial light modulator, and computer hardware-software to
      calculate and apply the correction. A finite-bit approximation to the conjugate
      phase is calculated and applied to the spatial light modulator to remove the
      aberrations from the optical beam. The experimentally determined Strehl ratio of
      the corrected beam is compared with analytical expressions for the expected
      Strehl ratio and shown to be in good agreement with those predictions.

PMID- 15143648
TI  - Continuous-wave, totally fiber integrated optical parametric oscillator using
      holey fiber.
AB  - We present, for the first time to our knowledge, a cw, all-fiber optical
      parametric oscillator that uses a holey fiber. The oscillator operates at 1.55
      microns and can yield an oscillating parametric signal that consists of a single
      line with a 30-dB extinction ratio and a 10-pm linewidth or that consists of
      multiple lines. In addition to the signal and the idler, five other pairs of
      spectral lines can be observed that are due to multiple parametric interactions.
      The source reaches threshold for a pump power of 1.28 W and saturates for pump
      powers in excess of approximately 1.6 W.

PMID- 15143649
TI  - Reflection of quadratic solitons at the boundary of nonlinear media.
AB  - We report experimental evidence of soliton reflection at the boundary of
      quadratic nonlinear media. The evolution of beams incident upon the interface of
      periodically poled LiNbO3 and uniform LiNbO3 is considered; in the whole device
      the linear refractive index is homogeneous. Linear beam transmission and soliton
      reflection at the nonlinear phase-mismatched boundary were observed. Numerical
      simulations that correspond to the experiments are also presented.

PMID- 15143650
TI  - Diffraction-limited polarized emission from a multimode ytterbium fiber amplifier
      after a nonlinear beam converter.
AB  - The multimode and depolarized output beam of a highly multimode diode-pumped Yb
      doped fiber amplifier is converted to a diffraction-limited, linearly polarized
      beam by a self-referencing two-wave-mixing process in an infrared-sensitive
      photorefractive crystal (Rh:BaTiO3). As much as 11.6 W of single-mode output is
      achieved with a 78% multimode-to-single-mode photorefractive conversion
      efficiency.

PMID- 15143651
TI  - Ultrahigh-gain bulk solid-state stimulated Brillouin scattering phase-conjugation
      material.
AB  - We report what is believed to be the first observation of phase conjugation by
      stimulated Brillouin scattering (SBS) in TeO2 single crystal. The observed very
      low threshold for phase-conjugate mirror (PCM) formation, high PCM reflectivities
      in this initial experiment, and commercial availability of material hold promise
      for a host of practical applications in the near future. The resultant steady
      state gain parameter, approximately 100 cm/GW, is to our knowledge the largest
      ever reported for any SBS material.

PMID- 15143652
TI  - Role of dispersion in multiple-collapse dynamics.
AB  - The multiple-collapse dynamics of ultrashort pulses along the propagation
      direction are investigated under conditions of both normal and anomalous group
      velocity dispersion (GVD). In the anomalous-GVD regime we find that collapse
      events can occur at locations in the medium many diffraction lengths beyond the
      initial collapse point, in contrast with the normal-GVD regime in which multiple
      collapse occurs within a diffraction length. Numerical simulations of a modified
      nonlinear envelope equation are found to be in good qualitative agreement with
      the observed lengths of the filaments.

PMID- 15143653
TI  - Cascaded Raman generation in optical fibers: influence of chromatic dispersion
      and Rayleigh backscattering.
AB  - We study experimentally the influence of chromatic dispersion and Rayleigh
      backscattering on cascaded Raman generation in silica optical fibers. Effects
      ranging from enhanced spectral broadening of the Stokes orders to generation of
      higher Stokes order at unexpected wavelengths are observed. Additionally, we show
      that four-wave-mixing processes can quench the noisy Rayleigh lasing lines
      generated in power Raman amplifiers. Our observations are confirmed by numerical
      simulations.

PMID- 15143654
TI  - Bifocal-polarization holographic lens.
AB  - We present a holographic lens with novel features recorded in an azopolymer film.
      Two holographic modulations, bulk birefringence and surface relief, are induced
      in the medium at the same time. The resultant holographic element has two focal
      planes, and the polarization of light in the focal points depends on the
      polarization of the incident light. Applications of this device for writing
      reading information in two planes simultaneously or separately are described.

PMID- 15143655
TI  - Superwide-angle coverage code-multiplexed optical scanner.
AB  - A superwide-angle coverage code-multiplexed optical scanner is presented that has
      the potential to provide 4 pi-sr coverage. As a proof-of-concept experiment, an
      angular scan range of 288 degrees for six randomly distributed beams is
      demonstrated. The proposed scanner achieves its superwide coverage by exploiting
      a combination of phase-encoded transmission and reflection holography within an
      in-line hologram recording-retrieval geometry. The basic scanner unit consists of
      one phase-only digital mode spatial light modulator for code entry (i.e., beam
      scan control) and a holographic material from which we obtained what we believe
      is the first-of-a-kind extremely wide coverage, low component count, high speed
      (e.g., microsecond domain), and large aperture (e.g., > 1-cm diameter) scanner.

PMID- 15143656
TI  - Fabrication of concave refractive microlens arrays in solgel glass by a simple
      proximity-effect-assisted reflow technique.
AB  - We report a simple method for fabricating a concave refractive microlens array
      (MLA) in solgel glass by using a proximity-effect-assisted reflow technique. The
      solgel concave refractive MLA that we fabricated had excellent surface
      smoothness; good dimensional conformity, with an 8.23% nonuniformity of the
      microlens elements; and structural perfection, with a biggest deviation of 1%
      from a perfect concave spherical crown. The relative error between the measured
      and the designed values of the concave MLA's focal length was only 1.83%.
      Compared with the conventional fabrication techniques for concave MLAs, the
      proposed method has significant advantages including simplicity, low cost, good
      element conformity, and smooth device surface.

PMID- 15143659
TI  - Addressing atoms in optical lattices with Bessel beams.
AB  - A method of synthesizing localized optical fields with zeros on a periodic
      lattice is analyzed. The applicability to addressing atoms trapped in optical
      lattices with low cross talk is discussed.

PMID- 15143660
TI  - Characterization of optically soft spheroidal particles by multiangle light
      scattering data by use of the neural-networks method.
AB  - A method for evaluating the size of optically soft spheroidal particles by use of
      the angular structure of scattered light is proposed. It is based on the use of
      multilevel neural networks with a linear activation function. The retrieval
      errors of radius R of the equivolume sphere and aspect ratio e are investigated.
      The ranges of the size of R, e, and the refractive index are 0.3-1.51 microns,
      0.2-1, and 1.01-1.02, respectively. The retrieval errors of the equivolume radius
      and aspect ratio are 0.004 micron and 0.02, respectively, for a three-level
      neural network (at a precisely measured angular distribution of scattered light).
      The retrieval errors of R and e for a one-level neural network are 2-5 times
      greater. The errors for a multilevel neural network increase faster than those
      for a single-level network.

PMID- 15143657
TI  - Analysis of high-reflectivity metal-dielectric mirrors for edge-emitting lasers.
AB  - A metal-dielectric mirror is shown as a simple solution for high-reflectivity
      coatings on cleaved-facet edge-emitting lasers, as well as a means to provide
      wavelength stabilization and spectral filtering. We show, through the use of a
      simple SiO2/Ti/Au coating, reflectivities better than 90% and a 25% reduction in
      the 30-dB linewidth of the output spectrum. Wavelength filtering and varying
      reflectivities are described as the result of multiple reflections and a coupled
      cavity effect.

PMID- 15143661
TI  - Statistical-mechanics theory of active mode locking with noise.
AB  - Actively mode-locked lasers with noise are studied employing statistical
      mechanics. A mapping of the system to the spherical model (related to the Ising
      model) of ferromagnets in one dimension that has an exact solution is
      established. It gives basic features, such as analytical expressions for the
      correlation function between modes, and the widths and shapes of the pulses
      [different from the Kuizenga-Siegman expression; IEEE J. Quantum Electron. QE-6,
      803 (1970)] and reveals the susceptibility to noise of mode ordering compared
      with passive mode locking.

PMID- 15143662
TI  - Extremely simple device for measuring 20-fs pulses.
AB  - We demonstrate an extremely simple frequency-resolved optical-gating device
      (GRENOUILLE) capable of measuring pulses with spectra wider than 100 nm. Its
      nearly all-reflective geometry minimizes the material dispersion, allowing
      accurate measurement of pulses as short as 19 fs.

PMID- 15143663
TI  - Ultrafast laser-driven x-ray spectrometer for x-ray absorption spectroscopy of
      transition metal complexes.
AB  - We report what are to our knowledge the first measurements of an x-ray absorption
      near-edge structure (XANES) spectrum of solvated iron pentacarbonyl by use of an
      ultrafast laser-driven plasma x-ray source. This source is operating at a 2-kHz
      repetition rate. Hard x radiation that might falsify the XANES measurements is
      suppressed by an x-ray optical setup that consists of a fiber-optic lens and a
      silicon single crystal.

PMID- 15143664
TI  - Terahertz time-domain spectroscopy of submonolayer water adsorption in
      hydrophilic silica aerogel.
AB  - We report a terahertz time-domain spectroscopy study of the adsorption of water
      in hydrophilic silica aerogel. The adsorbed water is in submonolayer form and
      shows properties of index of refraction similar to those of bulk water but
      different absorption properties.

PMID- 15143665
TI  - [Use of hydrogen peroxide for closing disulfide bridges in peptides].
AB  - The use of hydrogen peroxide for the formation of disulfide bridges was studied
      in 15 peptides of various lengths and structures. The oxidation of peptide thiols
      by hydrogen peroxide was shown to proceed under mild conditions without
      noticeable side reactions of Trp, Tyr, and Met residues. Yields of the
      corresponding cyclic disulfides were high and mostly exceeded those obtained with
      other oxidative agents, in particular, iodine. It was established that the use of
      hydrogen peroxide in organic medium also provided sufficiently high yields when
      large-scale syntheses of oxytocin and octreotide (up to 10 g) were carried out.
      The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004,
      vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143658
TI  - Tailored Gires-Tournois etalons as tunable dispersion slope compensators.
AB  - We present a novel concept of a tailored Gires-Tournois etalon structure and show
      that such a device is useful for the fabrication of a dispersion-slope
      compensator with an almost arbitrary dispersion profile and also with tunability
      in the dispersion slope.

PMID- 15143666
TI  - [Synthesis of lipophilic RGD-peptide derivatives].
AB  - Bishexadecyl ester of RDG peptide was synthesized in solution by the conventional
      methods of peptide chemistry in a total yield of 48%. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143668
TI  - [Role of histidine in ligand binding ability of hemoglobin gene].
AB  - The atomic and electronic structures of heme complexes with His, Gly, and Cys
      residues (Heme-His, Heme-Gly, and Heme-Cys) in the fifth coordination position of
      the Fe atom and with oxygen and nitrogen oxide molecules in the sixth Fe position
      were studied by the semiempirical quantum-chemical method PM3. A comparative
      analysis of internuclear distances showed that the strength of chemical bonding
      between the ligand molecules (oxygen and nitrogen oxide) is greater for Heme-Cys
      than for Heme-His and Heme-Gly complexes. Consequently, the strengthening of the
      chemical bond of the oxygen (or nitrogen oxide) molecule with Heme-Cys
      substantially weakens the chemical bond in the ligand molecule. The Mulliken
      population analysis showed that the electronic density of ligand (oxygen or
      nitrogen oxide) p-orbitals is transferred to the d-orbitals of the Fe atom, whose
      charge, calculated according to the Mulliken analysis, formally becomes negative.
      In the Heme-His complex with oxygen, this charge is substantially greater than in
      the complex with NO, and the oxygen molecule becomes polarized. No oxygen
      polarization is observed in the Heme-Cys complex, and the electron density
      (judging from the change in the Fe charge) is transferred to the coordinated
      sulfur atom. This is also characteristic of Heme-Cys complexes with nitrogen
      oxide. An analysis of charges on the atoms indicates that the character of
      chemical bonding of the oxygen molecule in Heme-Cys and Heme-Gly complexes is
      similar and basically differs from that in the case of the Heme-His complex. The
      English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol.
      30, no. 2; see also http://www.maik.ru.

PMID- 15143670
TI  - [Synthesis of monomoraprenyl- and monodolichylsuccinates and maleates].
AB  - The reactions of moraprenol and dolichol with succinic and maleic anhydrides in
      the presence of pyridine or triethylamine were studied, and the conditions were
      found for the efficient synthesis of moraprenyl and dolichyl hydrogen succinates
      and maleates. These may be of interest as analogues of moraprenyl and dolichyl
      hydrogen phosphates with modified anionic groups. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143671
TI  - [Synthesis, NMR and conformational studies of fucoidan fragments. VI. Fragments,
      content of alpha-(1--->2)-bound fucobioside unit].
AB  - A series of selectively sulfated di- and trisaccharide derivatives corresponding
      to the potential fragments of fucoidans with a (1-->2)-alpha-bound fucobioside
      unit were synthesized and studied by 1H and 13C NMR spectroscopy. NOE experiments
      and molecular modeling were used for a conformational analysis of the compounds
      synthesized. In the case of disaccharides, the experimental NOE values were found
      to agree with those obtained using modeling with the use of density functional
      theory (DFT) and differ from those resulting from modeling by the molecular
      mechanics MM3 force field. Trisaccharide fragments partially or completely
      sulfated in position 4 turned out to be correctly described by both MM3 force
      field and DFT computation. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143667
TI  - [Precursors of HLDF differentiation factor and ribosomal protein RPS21 have a
      common N-terminal sequence].
AB  - The mature differentiation factor HLDF, isolated from culture fluid, comprises 54
      aa, whereas the open reading frame of mRNA encodes a 97-aa protein. We presumed
      that the protein translation begins from the first ATG codon, whose environment
      mostly meets the requirements for the initiation point. Two more ATG triplets are
      localized in positions 48-50 and 100-102, i.e., in the area preceding the cDNA
      fragment that encodes the N-terminal fragment of the mature protein. The mRNAs of
      HLDF and the S21 ribosomal protein have previously been shown to be highly
      homologous, and, therefore, their differences appear to be derived from two point
      deletions in the cDNA of the HLDF-encoding sequence (a G residue in position 112
      and a C residue in position 224). As a result, the mature differentiation factor
      and RPS21 may be the products of translation from different open reading frames,
      the differentiation factor may be synthesized in the cell as a precursor, and its
      N-terminal sequence may be identical to that of RPS21. To test this hypothesis,
      we prepared recombinant RPS21 and the polyclonal antibodies to HLDF, full-size
      RPS21, and the C-terminal RPS21 peptide. Immunochemical staining by specially
      produced antibodies of native HL-60 cells and the same cells brought into
      apoptosis or differentiation confirmed that the precursor of the differentiation
      factor and the ribosomal S21 protein have a common N-terminal sequence and
      different cellular localizations. Neither an intron-containing gene nor a
      pseudogene with the nucleotide sequence corresponding to the HLDF cDNA was
      detected in the human genome or in the HL-60 cell line genome. On the basis of
      these facts, we propose a hypothesis of the molecular mechanism of the HLDF mRNA
      biosynthesis by means of posttranslational modifications of pre-mRNA of RPS21.
      The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004,
      vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143674
TI  - [Polar components of Black sea seaweed Colpomenia peregrina (Sauv.) Hamel].
AB  - GC-MS of trimethylsilyl derivatives of the compounds present in the butanolic
      extract of biomass of brown seaweed Colpomenia peregrina from the Black Sea aided
      in identification of 24 components, including aliphatic hydroxy and keto and
      aromatic acids, glycerol, mannitol, floridoside, and monosaccharides. The
      polysaccharide composition of the biomass was also studied, with high sodium
      alginate and laminaran contents and a comparatively low level of fucoidan being
      revealed. The polysaccharides were isolated from the biomass by fractional
      extraction and purified by precipitation or ion exchange chromatography. The
      structures of alginic acid and laminaran were deduced from 13C NMR spectra and
      confirmed, in the case of laminaran, by methylation analysis. The sodium alginate
      was shown to contain more guluronic (G) than mannuronic acid (M) residues, the
      M/G ratio being 0.48. Laminaran was demonstrated to be a beta-glucan with 1-->3
      linkages in its backbone and 1-->6 linkages in its branching points, which is
      characteristic of brown algae. Fucoidan turned out to be a complex
      heteropolysaccharide containing, in addition to fucose and sulfate, other neutral
      monosaccharides and uronic acids. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru

PMID- 15143673
TI  - [Synthesis of photoreactive neoglycolipid probes--instruments for studying
      membrane lectins].
AB  - A method for the synthesis of photoaffinity neoglycolipid probes with a highly
      efficient carbene-generating diazocyclopentadien-2-ylcarbonyl (Dcp) label, which
      can be radioiodinated under standard oxidation conditions, was developed. The
      probes are intended for incorporation into the lipid bilayer. They are lipophilic
      glycoconjugates on the basis of an amphiphilic aglycone built up from a
      diacylglycerol and a polyethylene glycol spacer (with a polymerization degree of
      9-16) bearing the Dcp label at the terminal unit. The location of the label in
      the aglycone provides the possibility of one-step preparation of a wide range of
      probes using various carbohydrate synthons. We have synthesized photoaffinity
      neoglycoconjugates containing the oligosaccharides: sialyl LewisX tetrasaccharide
      and A trisaccharide, which is specific to some tumor cells. A probe containing an
      inactive pentaol (aminodeoxyglucitol) was also synthesized to detect nonspecific
      binding. The Dcp label is bound to the probe molecule by ester bond; its lability
      under alkaline conditions facilitates the analysis of cross-linked products after
      photoaffinity labeling. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143676
TI  - [Interaction of new pyridylporphyrins with bovine serum albumin].
AB  - The interaction of meso-tetra(4-N-hydroxyethylpyridyl)porphyrin, meso-tetra(3-N
      hydroxyethylpyridyl)porphyrin, and their zinc complexes with bovine serum albumin
      (BSA) was studied by electronic spectroscopy, CD, and equilibrium dialysis at pH
      7.2. The titration of the porphyrins with BSA was accompanied by a decrease in
      light absorption and a bathochromic shift of the Soret band, as well as by the
      appearance of an isobestic point. The porphyrin interaction with BSA also led to
      the induction of positive CD spectra in the visible region, which is explained by
      the porphyrin sorption on the protein globule. The equilibrium dialysis helped in
      determining the stoichiometry of binding and the binding constants of the
      porphyrins under study with BSA using Scatchard plots. This interaction is
      nonspecific and reversible. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143675
TI  - [Inositol-containing sphingolipid from red algae Gracilaria verrucosa].
AB  - An unusual polar lipid was isolated from the red alga Gracilaria verrucosa.
      Inositol, sphingosine bases, fatty acids, and phosphate were identified by GC and
      GC-MS analysis among the products of its acid methanolysis. On the basis of the
      lipid composition, chromatographic behavior, chemical properties, and mass
      spectra, the inositolphosphoceramide structure was proposed for this lipid.
      Similar lipids were previously found only in fungi and some protozoa. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no.
      2; see also http://www.maik.ru.

PMID- 15143681
TI  - A genetic point of view.

PMID- 15143680
TI  - [New water-soluble analog of the fusion peptide of influenza virus hemagglutinin:
      synthesis and properties].
AB  - A water-soluble analogue F32 of the fusion peptide from the influenza virus
      hemagglutinin was synthesized. It consisted of 32 aa residues and retained the
      ability to interact with lipid membranes; its N-terminal sequence 1-24 coincided
      with that of the fusion protein from hemagglutinin (strain A/PR/8/34), whereas
      residues 25-32 (GGGKKKKK) provided its solubility in water. The peptide induced
      the conductivity fluctuations in planar bilayer lipid membranes characteristic of
      active fusion peptides. Conditions were found using CD spectroscopy under which
      the structure of F32 inside detergent micelles, where it can be studied by high
      resolution 1H NMR spectroscopy, is close to the structure of the peptide during
      its interaction with phospholipid liposomes. The English version of the paper:
      Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143679
TI  - [Steroidal polyols from Far Eastern starfish Henricia sanguinolenta and H.
      leviuscula leviuscula].
AB  - Two new asterosaponins, (20R)-3-O-beta-D-(2-O-methylxylopyranosyl)-24
      propylcholest-4-ene-3 beta,6 beta, 8, 15 alpha, 16 beta, 29-hexaol (sanguinoside
      A) and (20R,24S)-3-O-beta-D-(2,3,4-tri-O-methylxylopyranosyl)-5 alpha-cholestane
      3 beta, 4 beta, 6 beta, 8, 15 alpha, 24-hexaol (sanguinoside B), were isolated
      from two species of Pacific Far Eastern Starfish Henricia sanguinolenta and H.
      leviuscula leviuscula, collected in the Sea of Okhotsk. Both glycosides contain
      aglycones with pentahy-droxysteroid nuclei of similar structures, which are
      substituted at the 3-hydroxy group with differently methylated beta-D-xylosyl
      residues. Sanguinoside A has an unusual structure of its aglycone side chain,
      whereas sanguinoside B has a unique permethylated carbohydrate chain. In
      addition, laevisculoside G, a known glycoside, was identified in the H.
      leviuscula starfish. The structures of the isolated glycosides were established
      by interpreting their spectral data and by comparing their spectral
      characteristics with those of known compounds. The English version of the paper.
      Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143682
TI  - Imaging of congenital abnormalities.

PMID- 15143683
TI  - Case of the season. Massive tumor embolus filling the right ventricle and main
      pulmonary artery.

PMID- 15143678
TI  - [Palmitates of isomeric 15-oxygenated delta8(14)-sterols].
AB  - 3 beta-Hexadecanoyloxy-5 alpha-cholest-8(14)-en-15-one, 3 alpha-hexadecanoyloxy-5
      alpha-cholest-8(14)-en-15-one, 15 beta- hexadecanoyloxy-5 alpha-cholest-8(14)-en
      3 beta-ol, 15 alpha-hexadecanoyloxy-5 alpha-cholest-8(14)-en-3 beta-ol, 15 beta
      hexadecanoyloxy-5 alpha-cholest-8(14)-en-3-one, and 15 alpha-hexadecanoyloxy-5
      alpha-cholest-8(14)-en-3-one were synthesized and their chromatographic and 1H
      NMR characteristics were determined. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143677
TI  - [Immunochromatographic analysis of 2,4-dichlorophenoxyacetic acid and simazine
      using monoclonal antibodies labelled with colloidal gold].
AB  - A method of the competitive immunochromatographic assay of the pesticides 2,4-D
      (2,4-dichlorophenoxyacetic acid) and simazine (2-chloro-4,6-bis(N-ethylamino)
      1,2,5-triazine) in aqueous samples was developed. Monoclonal antibodies to these
      pesticides labeled with colloidal gold were used to visualize the results. The
      sensitivity of the 2,4-D and simazine assay is 12 ng/ml, and the time of analysis
      is 3-7 min. The method does not differ in sensitivity from the competitive EIA
      using conjugates of monoclonal antibodies to the pesticides with horseradish
      peroxidase; however, the time of the EIA is 1.5 h. The immunochromatographic
      method of the pesticide detection is available and simple and may be recommended
      for the development of assays of any other low-molecular compounds. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no.
      2; see also http://www.maik.ru.

PMID- 15143672
TI  - [Synthesis and immunomodulating activity of new diglycopeptides of of
      glycyrrhizinic acid and it's 30-methyl ester].
AB  - New amino acid derivatives of glycyrrhizic acid and its methyl ester were
      selectively synthesized using active N-succinimide esters. The compounds with
      residues of glycine ethyl ester and alanine methyl and butyl esters increased the
      level of agglutinins and hemolysins in blood serum of mice two- to threefold in
      comparison with the control upon parenteral administration at a dose of 2 mg/kg
      for 14 days. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

PMID- 15143685
TI  - Prenatal and postnatal imaging of spinal dysraphism.

PMID- 15143684
TI  - Congenital malformations of the brain: prenatal and postnatal imaging.

PMID- 15143686
TI  - Congenital anomalies of the fetal/neonatal chest.
AB  - The ability to identify and confidently diagnose a wide range of congenital fetal
      thoracic lesions has increased tremendously in the past 2 decades with the
      emergence of high-resolution sonography and ultrafast MRI sequences. Imaging
      studies constitute a vital component in the diagnosis of these lesions, whether
      in the fetal, neonatal or childhood periods. In addition to providing a road map
      for potential intervention, imaging techniques have provided important
      information about normal development, natural history, and prognosis. In the
      prenatal stage, these features aid in family counseling, pregnancy management,
      and the identification of a subgroup of patients who may benefit from fetal
      intervention. In the neonatal and childhood periods, imaging studies facilitate
      timely diagnosis and institution of appropriate therapeutic strategies.

PMID- 15143688
TI  - Cross-sectional imaging in congenital anomalies of the heart and great vessels:
      magnetic resonance imaging and computed tomography.

PMID- 15143689
TI  - Congenital abnormalities of the gastrointestinal tract.

PMID- 15143690
TI  - Congenital abnormalities of the genitourinary system.

PMID- 15143669
TI  - [Activation of the RIG-I gene, coding for DEXH/D-protein in infection of RH cells
      by tick-borne encephalitis virus].
AB  - It was demonstrated by subtractive hybridization that the infection of a human
      embryonic kidney cell line with tick-borne encephalitis virus causes an
      approximately tenfold transcription activation of the RIG-1 gene, which encodes a
      protein of the DExH/D-box-containing RNA helicase family. A possible involvement
      of the protein in antiviral cell systems is discussed. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also
      http://www.maik.ru.

PMID- 15143692
TI  - Prenatal diagnosis and imaging of genetic syndromes.

PMID- 15143693
TI  - [Traffic accidents--the national killer].
AB  - Traffic accidents are the most prevalent cause of death in developed countries
      between the ages of 1-33 years. In spite of a low motorization level in Israel,
      the rate of injury per 100,000 residents in Israel (2.8) was higher than in the
      US (1.8), NZ (1.7), Canada (1.7), Japan (1.3) and most European countries. The
      worst injuries were among pedestrians; particularly children aged 1-9 years and
      elderly (70+ years). In the past decade there have been significant advances in
      trauma care in Israel. Major strides included the foundation of trauma centers in
      hospitals, the establishment of the National Council for Trauma and the National
      Center for Trauma and Emergency Medicine Research at the Gertner Institute that
      coordinates the national trauma registry. One of the primary aims of the registry
      was to provide data to support decision-makers in setting national policy for
      accident prevention. The Israeli Police Department provides data on traffic
      accident victims to the Israeli Central Bureau of Statistics (CBS) which
      publishes the national figures. In their article in this edition of the journal,
      Dr Peleg and Dr. Aharonson-Daniel present a grave concern regarding the fact that
      details of over 50% of hospitalized traffic accident victims were not reported to
      the CBS by the police, including data on the severely injured casualties. Traffic
      accidents are a major cause of loss of life and disability, creating a heavy
      economic burden on the state and the health care system. Hence, the authors
      recommend establishing a national database which will combine data from medical
      and other sources and present the complete comprehensive picture of traffic
      accident injuries. Such a database will improve the decision-making process,
      providing more focused data to enhance the preparation and dissemination of
      appropriate injury prevention policies.

PMID- 15143694
TI  - [Pasteurella multocida infections--10 years' experience].
AB  - Dog and cat bites are commonly seen at emergency rooms, but have been
      inadequately characterized. This study attempted to characterize the clinical
      features of 10 patients from whom P. multocida was cultured. During the past 10
      years, 108 patients have been hospitalized for pet bites, at a rate of 3.4/10,000
      hospitalizations. Five patients had a documented exposure to cats, 3 to dogs, and
      two had an unknown exposure. The mean age was 50.8 years (+/- 20.5) and 80% were
      men. An average delay of 5.7 days was noted from exposure to hospitalization, and
      additional 4.4 days until P. multocida was characterized. P. multocida was
      cultured from wounds in six patients, and three patients had bacteremia; another
      patient had septic arthritis. Six patients needed debridement and the average
      hospital stay was 11.7 days (3 times our hospital's average). Animal bites may
      take a complicated course. Our findings call for reassessment of the need for
      prophylaxis in animal bites.

PMID- 15143691
TI  - Congenital abnormalities of the musculoskeletal system: perinatal evaluation and
      long-term outcome.
AB  - Many musculoskeletal malformations can be detected by prenatal US. Whether
      isolated or part of a syndrome, these anomalies can have a significant impact on
      the entire life of the individual. Nonfatal conditions may be subtle and become
      more recognizable in the second and third trimester. After delivery, radiography
      helps confirm the diagnosis. US, CT, and MRI all have a role in imaging the
      primary abnormality, the follow-up effects of treatment, and in monitoring for
      potential complications that may develop over time. Three-dimensional imaging has
      an increasing role, in US, CT, and MRI, both in the prenatal and postnatal
      periods.

PMID- 15143695
TI  - [Contralateral hemothorax: a late complication of subclavian vein
      catheterization].
AB  - Central venous catheterization is extensively used in unstable patients who need
      hemodynamic monitoring and in patients who require prolonged treatment such as,
      chemotherapy, antibiotics therapy, parenteral nutrition, or temporary
      hemodialysis. Subclavian vein catheterization is the preferred approach for
      hemodialysis, especially as it does not restrict the patient. Most of the
      complications related to this procedure are insignificant, however, occasionally
      they may be life threatening and require surgical intervention. We present a case
      study of a 77-year-old woman suffering from chronic renal failure. A subclavian
      catheter was inserted, and the patient started hemodialysis. Three weeks later,
      during hemodialysis, she complained of right upper abdominal and right chest
      pain. Chest X-ray showed a moderate to large right pleural effusion, with
      pleurocentesis confirming the presence of hemothorax.

PMID- 15143687
TI  - Ultrasound of congenital heart disease: a review of prenatal and postnatal
      echocardiography.

PMID- 15143696
TI  - [The effect of spouse participation in cardiac rehabilitation program on
      patients' compliance and exercise level].
AB  - BACKGROUND: Exercise-based cardiac rehabilitation programs have proven to be
      associated with decreased morbidity and mortality after cardiac events.
      Unfortunately, attendance is often poor, and long term compliance is low. This
      study examined the effect of the active participation of spouses in the exercise
      program on the compliance and physical fitness level of their partners. METHODS:
      During the years 1998-2001, 24 couples joined our cardiac rehabilitation program.
      The couples were divided into 2 groups on the basis of their medical status. In
      Group 1--Rehabilitation program (n = 14); one of the couple had suffered a
      myocardial infraction or underwent a coronary bypass surgery at least 3 weeks
      before starting the program. In Group 2--secondary prevention (n = 10); one of
      the couple had a medical history of cardiac disease. The third Group included the
      spouse. Each group was compared with a matched control group based on their
      medical condition. The parameters that were measured were: the number of sessions
      attended, basic and final physical training level. RESULTS: In the rehabilitation
      groups, the participants attended a larger number of sessions (87.3 + 17)
      compared to control (47.7 + 6) (p < 0.05). There was no difference in the basic
      training level between the groups (3.5 + 0.2 METS; compared with 3.4 + 0.2 METS)
      (P = 0.5) and both groups had similarly improved their training level by 0.79 +
      0.1 METS compared with 0.6 + 0.1 METS in the control group (p = 0.2). In the
      secondary preventive groups, the control group attended a larger number of
      sessions (51 + 13 compared with 31.2 + 6 sessions) (p < 0.02). There was no
      difference in the basic training level between groups 3.7 + 0.3 METS compared
      with 4.2 + 0.2 in the control group (p = 0.2). However, at the end of the
      training period, the control group showed greater improvement in their training
      level by 0.7 + 0.2 METS compared to 0.3 + 0.1 METS (p < 0.05). The spouses
      themselves had attended a greater number of sessions (45 + 10 compared with 37 +
      6 in the control group) (p = 0.2). There was no difference between those groups
      in the training level at baseline and at the end of training period. CONCLUSION:
      Active support during the rehabilitation program may improve the rates of
      participation but in the secondary prevention program active spouse support may
      encourage early dropout.

PMID- 15143697
TI  - [Reasons for failure in gait rehabilitation after stroke, hip fracture and lower
      limb amputation].
AB  - During a period of 12 months, 136 patients were discharged from the
      rehabilitation unit into the community. This article retrospectively reviewed the
      discharge letter in the medical dossiers for these cases. The patient group
      included: seventy-one patients recovering after a first stroke and 25 after a
      recurrent stroke, 13 cases were operated after traumatic hip fracture, 15 were
      after below-knee amputation and one, after above-knee amputation. Eleven patients
      had other diseases or injuries. Patients were considered ambulators if they were
      able to walk independently, with or without assisting device, inside the
      department for a distance of at least 5 meters. Nonambulating patients could not
      walk or could walk only a few steps with full assistance, for a distance of less
      than 5 meters. Only 9 patients remained wheelchair dependents at the end of the
      rehabilitation period (6 after stroke, one after hip fracture and 2 amputees).
      The 6 stroke patients were all unable to support their body weight over the
      hypotonic paralyzed leg or to balance between the leg and the walking device. The
      only patient in this subgroup after hip fracture suffered from hemiplegia,
      contralateral previously operated hip fracture and Parkinson disease. Among the
      two amputees, one refused to continue the rehabilitation program and the other,
      suffered from motor and cognitive disorders following three episodes of stroke.

PMID- 15143699
TI  - [Homeless-disabled people--medical, moral and social problem].
AB  - Many factors contribute to homelessness, including extreme poverty, extended
      periods of unemployment, disruption of regular sources of income and employment,
      deinstitutionalization and substance abuse. As a result, the needs of the
      homeless are both broad and complex. This assessment is based on literature
      reviews and reviews of local documents and reports. For homeless people,
      healthcare competes with more immediate needs, such as obtaining adequate food
      and shelter and it is our duty as a society to help.

PMID- 15143698
TI  - [Noise-induced hearing loss--factors affecting worker's decision to submit a
      disability claim].
AB  - Noise-induced hearing loss is recognized worldwide as a prevalent work-related
      morbidity and is the most common compensated occupational disease in Israel.
      Despite extended legislation, hearing conservation programs, surveillance and
      biological monitoring (by audiometry) of work sites and workers, the burden of
      this injury remains high. As a rule, afflicted workers refrain from filing
      compensation claims and do so only at later stages when both subjective and
      objective evidence of advanced hearing loss is present. We have evaluated the
      determinants that seem to influence the decision of an individual worker to file
      a claim. We found that the major determinants are subjective perception of the
      level of hearing disability and clinical symptoms such as: tinnitus (OR = 3.3
      with CI 95% = 2.1 5.2), verbal communication disturbances (OR = 2.7, 95% CI = 1.9
      3.8), complaints of dizziness (OR = 1.9, 95% CI = 1.4-2.5), severity of hearing
      impairment (by audiometry with OR = 1.04, 955 CI = 1.02-1.06) and musculoskeletal
      complaints (OR = 1.6, 95% CI = 1.2-2.2). These findings attest to the relatively
      late stage in the development of noise-induced hearing loss at which workers file
      a claim for compensation and rehabilitation. In order to alleviate the burden of
      this injury in the future and encourage workers to approach the National
      Insurance Institute at an earlier stage, we suggest several ways of intervention
      and improving the awareness of all parties concerned.

PMID- 15143702
TI  - [Bacteriophages as antibacterial agents].
AB  - Bacteriophages are viruses that only infect bacteria. They have played an
      important role in the development of molecular biology and have been used as anti
      bacterial agents. Since their independent discovery by Twort and d'Herelle, they
      have been extensively used to prevent and treat bacterial infections, mainly in
      Eastern Europe and the former Soviet Union. In western countries this method has
      been sporadically employed on humans and domesticated animals. However, the
      discovery and widespread use of antibiotics, coupled with doubts about the
      efficacy of phage therapy, led to an eclipse in the use of phage in medicine. The
      emergence of antibiotic resistant bacteria, especially strains that are multiply
      resistant, has resulted in a renewed interest in alternatives to conventional
      drugs. One of the possible replacements for antibiotics is the use of
      bacteriophages as antimicrobial agents. This brief review aims to describe the
      history of bacteriophage and early clinical studies on their use in bacterial
      disease prophylaxis and therapy, and discuss the advantages and disadvantages of
      bacteriophage in this regard.

PMID- 15143703
TI  - [Health care systems and impossibility theorems].
AB  - Health care systems, amongst the most complicated systems that serve mankind,
      have been in turmoil for many years. They are characterized by widespread
      dissatisfaction, repeated reforms and a general perception of failure. Is it
      possible that this abominable situation derives from underlying causes, which are
      inherent to the most basic elements of these systems? Those elements compromise
      the use of words and definitions in the formulation of their principles and their
      way of action, in their logical structure as well as in the social order in which
      they exist. An in-depth investigation of these elements raises findings that may
      negate the basic feasibility of the success of such complex systems, as currently
      known in the western world. One of the main elements of the democratic regime is
      its system of decision/choice making, i.e. the majority vote. But, already in the
      nineteenth century, it was discovered that a majority was an intransitive
      ordering and did not produce a consistent definition of a preference. The Marquis
      of Condorcet in his famous 1785 "Essai sur l'application de l'analyse a la
      probabilite des decisions rendues a la plurite des voix", clearly demonstrated
      that majority decisions might lead to intransitivity and an indeterminancy in
      social choices. On the basis of his discoveries, it was later shown that
      legislative rules may lead to the choice of a proposal that is actually opposed
      by the majority, or to a deadlock and therefore, to socially undesirable
      implications. Subsequent to these theories of Condorcet, which became known as
      "The Paradox of Condorcet", many papers were published in the 19th and 20th
      centuries regarding the issue of problems dealing with individual preferences
      leading to social order--a complex procedure of, amongst others, aggregation in a
      defined axiomatic framework. During the twentieth century it became astoundingly
      manifest that certain issues, although correctly attacked logically, could not be
      resolved. Two such famous results are Kurt Godel's seminal paper in 1931: "Ueber
      formal unentscheidbare Saetze der Principia Mathematica and verwandter System I"
      and Arrow's Nobel Prize winning "Impossibility Theorem" (Social Choice and
      Individual Values, 1951). Godel showed, unequivocally, that there is an enormous
      gap between what is being perceived as truth and what in fact can be proven as
      such. Arrow showed that the translation of individual preferences into a social
      order is impossible--except in a dictatorship. The unsolved controversies
      concerning the desirable or ideal structure of health care systems are impinged
      upon by these findings generally, and, in the case of the impossibility theorem,
      also directly. There is the impossibility of aggregating preferences and, at a
      deeper level, the impossibility of defining certain fundamental values, coupled
      with the problematic use of certain words, the absence of the possibility of
      creating, on a logically defined base, a complex system, complete and
      comprehensive in its own right. This is added to the fact that according to the
      elaboration by Stephen Wolfram in "A New Kind of Science", it is not easy to
      reduce complicated systems to simple components and to predict the continuation
      of their development even from simple basic laws without complicated
      calculations. All of these factors impede the construction of satisfying health
      care systems and leave obvious problems which overshadow the structure and the
      operation of health care systems.

PMID- 15143704
TI  - [Prenatal diagnosis of fetal neoplasms].
AB  - A variety of neoplasms can develop in each fetal organ. Most fetal neoplasms can
      be detected by ultrasonographic examination. Cancer appearing either at birth or
      within the first month of life occurs in 36.5 per million liveborn infants. The
      death rate is 6.24-7.6 per million live births. This article briefly reviews the
      sonographic findings in the most common fetal neoplasms and presents the authors'
      experience in the prenatal ultrasonographic diagnosis of fetal neoplasms:
      intracranial fetus-in-fetu, adrenal neuroblastoma and mesoblastic nephroma.

PMID- 15143701
TI  - [Our experience with the medical rehabilitation of homeless-disabled people].
AB  - During the last two years, 11 homeless-disabled people were treated at our
      rehabilitation ward. All of the patients were Jewish, six were new immigrants
      from Russia, their age ranged between 34 to 60 years, most of these patients had
      completed at least high school education, and all had managed to have a "normal"
      social-working life until the crisis which led them to the street. Six became
      alcoholics and one was a narcotic-drug user. None of these patients suffered from
      malnutrition or mental disorder, and after the rehabilitation process was over,
      they became independent, performing the activities of daily living. Most of them
      decided to return to their previous street--living place, despite their
      disabilities. This new combination of relatively young disabled-homeless people
      at our rehabilitation facility demands novel and different rehabilitation
      approaches.

PMID- 15143700
TI  - [Road traffic accidents--severe injuries. Decision-making on the basis of partial
      data].
AB  - BACKGROUND: Road traffic accidents are the cause of approximately one quarter of
      trauma hospitalizations in Israel. A comparison of figures on severe traffic
      injuries, as published by the Israeli Central Bureau of Statistics (CBS) and the
      Israeli Police with data from registries in medical systems, revealed significant
      disparities. AIMS: To present gaps between registries and the possible
      consequences that presenting incomplete data to decision makers may have on their
      ability to set policy for reducing road traffic accidents. RESULTS: The number of
      severe injuries according to the CBS, the National Council for Road Safety and
      the Israeli Police ranges from 3,378 to 2,573 per year, for the period 1998-2000.
      During the same time period, the national trauma registry that recorded data at
      only eight hospitals (of the 24 hospitals in the country), noted a total of 4,442
      to 4,800 patients per year. The Ministry of Health's data, that includes figures
      from most of the hospitals in the country, reports between 10,290 to 11,009 road
      traffic accident hospitalizations per year for this same period of time. The CBS
      data is the formal national data, hence the database which decision makers use
      when considering the number of casualties due to road accidents consists of less
      than half of the actual number of cases. Furthermore, it is not a representative
      sample. When decisions are made without data, one uses common sense and reason.
      However, when the decision maker is presented with information, he assumes that
      these are valid, reliable, representative, well established data and relates to
      the information as such in the decision making process. If data is misleading,
      decisions may be ill-advised. SUMMARY AND CONCLUSION: Gaps in information are
      presented, posing a question on the possible effect that the interpretation of
      partial data by decision makers may have on the decisions they make. It is
      strongly advocated that collaboration is needed between police and health
      agencies and that a system for collecting and analyzing data on road traffic
      casualties be established to combine health and police data. The existence of a
      reliable, complete and valid database is essential in order to succeed in the
      important battle to reduce morbidity and mortality from road traffic accidents.

PMID- 15143706
TI  - [Western bio-ethics--Israel between North America and Europe].
AB  - In an attempt to re-structure and formulate western bio-ethics in the '80's, the
      four principles of beneficence, non-maleficence, autonomy and justice were
      promulgated in North America and the United Kingdom. Extensive criticism was
      leveled against this endeavor, as being erroneous in principle or substantially
      inadequate. Furthermore, European opponents of this effort claimed that the
      Continent's 'true' set of values greatly differs from those of North America,
      hence negating attempts for global bio-ethics based on these principles. In this
      review the principles of modern American bio-ethics are presented and criticisms
      presently deliberated in Europe are introduced, while offering alternative
      principles. Israel's unique position is demonstrated by its legislation on issues
      such as the national health system, organ transplantation, the right to refuse
      medical treatment and stem cell research, all confirming that Israel begs to
      differ. We conclude that European values have much in common with Israel's
      tradition and culture, commending due modification of our ethical conceptions and
      training programs. The coming years should be characterized by constant dialogue
      between the proponents of European and American values, while Israel's individual
      standpoint is maintained.

PMID- 15143707
TI  - [Iatrogenic fetal death--ethical and juridical issues].
AB  - What are the rights of a fetus to live and exist? Is respecting the rights of the
      pregnant woman over her body and her independence the primary concern to be taken
      into account? Or does the fetus of a certain age have it's own rights, which
      should prevail when cardinal decisions about it's future life need to be made?
      How should the parturient's doctor act when contradicting interests and needs
      exist between those of the pregnant woman and her fetus? To whom does the
      practitioner owe his or her primary loyalty? Can any of the involved "parties"
      prosecute the physician for acting on behalf of one of them, while injuring the
      rights of the other? In the great majority of cases, the above presented dilemmas
      do not need to be dealt with, as there is a complete overlap between the
      expectations of the future mother and the interests of her future child. Indeed
      the legislator attended to these issues, and considered the medical risks, the
      ethical and juridical aspects, and the philosophical theories and religious
      beliefs. However, a few difficult cases with no authoritative recommendations or
      guidance still exist. Our case report is an example of such a dilemma, in which
      the rights of a fetus at term, with presumed normal anatomical and intellectual
      potential, were scarified and violated, causing it's death. This dismal outcome
      is apparently the consequence of the mother's intellectual incompetence. At the
      same time, the medical and juridical institutions backed up her refusal to have a
      cesarean section that could have saved her fetus, considering her (incompetent)
      decision as prevailing, leaving the fetus to perish in its mother's womb, and
      trampling irrevocably it's right to live. In view of this case, we describe the
      chain of events that took place, involving the reader in the medical-ethical
      juridical dilemmas. We intend to bring the subject to an overall profound,
      valuable, professional and multidisciplinary debate in order to establish
      acceptable guidance and directives in similar cases in the future.

PMID- 15143705
TI  - [Posterior tibial tendon dysfunction].
AB  - Posterior tibial tendon dysfunction is the most common cause of acquired flatfoot
      in adults. The posterior tibial tendon is the primary dynamic stabilizer of the
      medial longitudinal arch of the foot. Various histological alterations in the
      tendon substance disrupt the normal linear structure of the collagen fibers. As a
      result the tendon weakens, elongates, tears and its function is compromised. This
      in turn places the static stabilizers of the arch under excessive stress, which
      eventually leads to their collapse and formation of pes planovalgus deformity.
      Many etiologies have been proposed as an underlying cause of posterior tibial
      tendon dysfunction. The average age at the time of presentation is forty years
      and many of the patients are women, white, obese and suffer from hypertension.
      The diagnosis is mainly based on clinical findings and supported by radiographic
      findings. Posterior tibial tendon dysfunction was classified by Johnson and Strom
      according to the appearance of pes planovalgus deformity, its flexibility and the
      development of arthritic changes in the subtalar and ankle joints. In Stage I
      there is no deformity, in Stage II there is a flexible deformity, in stage III
      there is a rigid deformity and in stage IV there is an involvement of the ankle
      joint secondary to long standing rigid deformity of the hindfoot. The initial
      treatment for any stage should be non-operative and includes immobilization and
      anti-inflammatory drugs for the acute phase and different kinds of orthotics for
      the chronic phase. Failure of the non-operative treatment is an indication for
      surgery. The surgical procedures for the first stage include soft tissue
      debridement with or without tendon transfer. The surgical procedures for second
      stage include tendon transfer combined with various osteotomies or joint fusions.
      The surgical procedures for the third and fourth stages are triple arthrodesis
      and pantalar arthrodesis respectively.

PMID- 15143708
TI  - [American Geriatrics Society, Annual Scientific Meeting, Baltimore May 2003].

PMID- 15143709
TI  - [Homeless with a giant cauliflower-like tumor on the chest wall].

PMID- 15143710
TI  - [The clinical application and research of Chinese patent compound formulas].

PMID- 15143711
TI  - [Effect of yangjing zhongyu decoction on matrix metalloproteinase-9 expression in
      endometrium and sex hormone regulation in women with cryptogenic infertility].
AB  - OBJECTIVE: To investigate the effect of Yangjing Zhongyu decoction (YZD) on
      metalloproteinase-9 (MMP-9) and its inhibitor-1 (TIMP-1) expression and sex
      hormone regulation in mid-luteal phase endometrium of women with cryptogenic
      infertility. METHODS: In situ hybridization and reverse transcription-polymerase
      chain reaction method was used to detect MMP-9 and TIMP-1 mRNA, and
      radioimmunoassay was used to determine levels of serum estradiol (E2) and
      progesterone (P) synchronously, of 22 infertile women during mid-luteal phase.
      RESULTS: After treatment, the mid-luteal serum E2 and P level was 451.501 +/-
      226.342 pmol/L and 46.502 +/- 19.948 nmol/L respectively, significantly higher
      than that before treatment (304.656 +/- 135.853 pmol/L and 33.782 +/- 15.459
      nmol/L respectively), the difference was significant (P < 0.01). Staining of MMP
      9 mRNA positive granules in cytoplasm and nuclei of adeno-epithelial cell mid
      luteal phase endometrium deepened significantly, but the change in mesenchym was
      insignificant. The MMP-9 mRNA expression after treatment was 0.617 +/- 0.186
      (grey level), significantly higher than the level before treatment (0.490 +/-
      0.370), comparison between them showed significant difference (P < 0.05). Change
      of TIMP-1 mRNA expression in adeno-epithelial and mesenchym before and after
      treatment was insignificant (0.588 +/- 0.191 vs 0.621 +/- 0.146, P < 0.05).
      Correlation analysis showed that the quantitative difference of P value before
      and after treatment was positively correlated with the difference of MMP-9 mRNA
      before and after treatment (r = 0.682, P < 0.01). CONCLUSION: YZD could soothen
      Gan and nourish Shen, raise the level of mid-luteal phase serum P, and further
      promote MMP-9 gene expression in endometrium to benefit the degradation of
      extracellular matrix of endometrium, and facilitate for blastocyst implantation.

PMID- 15143712
TI  - [Therapeutic effect of Chinese herbal medicines for nourishing blood and
      reinforcing shen in treating patients with anovulatory sterility of shen
      deficiency type and its influence on the hemodynamics in ovarian and uterine
      arteries].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of Nuzhen Yunyu Decoction
      (NYD, a Chinese recipe for nourishing blood and reinforcing Shen) and its
      influence on the hemodynamic parameters in ovarian and uterine arteries. METHODS:
      Sixty-eight patients were randomly divided into two groups at the ratio of 2:1,
      45 in the TCM group treated with Chinese medicine and 23 in the control group
      treated with clomiphene citrate. Menstrual cycle were taken as the indexes for
      clinical observation; basal body temperature, cervical mucus, vaginal exfoliative
      cells, serum hormones and B ultrasonic examination were taken as the indexes for
      ovulation and pregnancy assessment. The hemodynamic parameters of uterus and
      ovary were determined by using color Doppler ultrasonography, and the growth of
      follicles and ovulation, thickness of uterine endometrium were also monitored
      continuously. RESULTS: Results of 3 cycles treatment and 1 year follow-up study
      showed that the ovulation promoting rate, pregnancy rate and abortion rate in the
      two groups were similar, but the treated group showed better effects than that of
      control group, in such aspects as regulating menstruation, promoting growth and
      development of follicle, strengthening endometrium, improving blood supply and
      circulation of uterine and ovary (P < 0.05, P < 0.01). CONCLUSION: NYD has the
      effects of ovulation promotion and holistic regulation of reproductive system.

PMID- 15143713
TI  - [Effect of Chinese herbal treatment on the efficiency of blocking CD antigen and
      on prolactin and progesterone in women with recurrent spontaneous abortion].
AB  - OBJECTIVE: To explore the effect of Chinese herbal medicine Baotai Granule (BTG,
      a self-made preparation) on CD antigen blocking efficiency, prolactin (PRL) and
      progesterone (P) in patients with recurrent spontaneous abortion (RSA). METHODS:
      Thirty-four women suffered from RSA were treated with BTG, twice every day, 1
      package (10 g) in each time by orally intake. Changes of the efficiency of serum
      blocking antibody in them to the CD antigen in their husband's peripheral T
      lymphocytes before and after treatment were observed. And the changes of blood
      levels of PRL and P were also monitored. RESULTS: Fetus had successfully
      protected in 30 women (88.2%), in them, the efficiency of blocking to CD3, CD4
      and CD8 after treatment were all higher than that before treatment, and levels of
      PRL and P in peripheral blood increased along with the increase of gestational
      age, while no obvious change was found in those who failed to complete pregnancy.
      CONCLUSION: Chinese herbal medicine could protect the fetus by regulating the
      response between endocrine and immunity network during pregnancy.

PMID- 15143714
TI  - [Exploration on the relationship between positive antisperm antibody and nitric
      oxide level of infertile patients and on integrative Chinese and Western medicine
      treatment].
AB  - OBJECTIVE: To study the relationship between the positive antisperm antibody
      (AsAb) and nitric oxide (NO) content in blood of infertile patients and the
      therapeutic effect of integrative Chinese and western medicine (ICWM) treatment
      on the disease. METHODS: Infertile patients, 75 of AsAb positive and 68 of AsAb
      negative were selected to observe the mature partuient rate and abortion rate.
      Serum NO level were measured before treatment to observe the relationship between
      NO and positive AsAb. Patients were treated with ICWM and followed-up for five
      years. RESULTS: Mean value of serum NO in patients with positive AsAb was
      significantly higher than that in fertile women, and there was no significant
      difference between patients with negative AsAb and fertile women (P < 0.01). In
      the 5 years after treatment, the mature partuient rate between the two groups
      showed insignificant difference (P > 0.05). CONCLUSION: AsAb positive and NO
      level abnormal may interfere mutually, to intervent the reproductive process.
      ICWM therapy could effectively regulate auto-immunity and endocrine function, and
      make the infertile patients obtain satisfactory efficacy.

PMID- 15143715
TI  - [Analysis on therapeutic effect of Western and Chinese drug in treating
      intrahepatic cholestasis pregnancy].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and
      S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy
      (ICP) and improving prognosis of perinatal newborn babies. METHODS: Sixty in
      patients of ICP were randomly divided into two groups, the group A treated with
      YCHD and the group B treated with SAM. The symptom of itching and serum
      biochemical indexes, including glycocholic acid, bilirubin and transaminase, were
      observed after 3 weeks treatment, and the prognosis of perinatal newborn babies
      between the two groups was compared after delivery. RESULTS: After treatment, the
      symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase
      improved significantly (P < 0.05) in both groups, and the prognosis of newborn in
      the two groups was similar (P > 0.05). CONCLUSION: Both YCHD and SAM could
      effectively treat ICP. The former is rather cheaper, so it is more feasible for
      spreading.

PMID- 15143717
TI  - [Effect of jiangtang bushen recipe in intervention treatment of patients with
      impaired glucose tolerance].
AB  - OBJECTIVE: To evaluate the intervention effect of diet, exercise and Jiangtang
      Bushen Recipe (JBR, a Chinese herbal recipe) in preventing the progress of
      patients with impaired glucose tolerance (IGT) to diabetes mellitus (DM) type 2.
      METHODS: Fifty-one patients with IGT, with their diagnosis conformed to the
      diagnosis standard of WHO, 1999, were randomly divided into the control group (n
      = 26) and the TCM group (n = 25). Patients in the control group attended to the
      educational course for DM and received dietotherapy and kinetotherapy, and to
      those in the TCM group, under these treatments, JBR was given additionally. Oral
      glucose tolerance test (OGTT), body weight index (BWI), levels of blood lipids
      and fasting insulin of all the patients were examined after 3 months, 6 months
      and 12 months of treatment. The total observation time was 1 year. RESULTS:
      Except the 6 cases out of the 51 patients (11.7%), on whom the observation
      discontinued, in the control group, as compared with before treatment, levels of
      fasting insulin and fasting blood glucose after treatment were not changed
      significantly (P > 0.05), also insignificant difference was shown in levels of
      total cholesterol (TC) and triglyceride (TG), though the two indexes lowered
      slightly after treatment (P > 0.05), but significant difference was shown in
      comparison of OGTT/2 h, blood glucose and BWI (P < 0.05). While in the TCM group,
      fasting blood glucose was changed insignificantly (P > 0.05), but there was
      significant difference in comparison of fasting insulin, TC, BWI, OGTT/2 h and
      plasma glucose levels (P < 0.01) respectively before and after treatment. At the
      end of the study, the cumulative cases with conversion to diabetes were 3 (13.6%)
      in the control group, and 1 (4.3%) in the TCM group, chi 2 test showed
      insignificant difference in comparison of diabetes conversion rate between the
      two groups (P > 0.05), however, the TCM group showed a better year conversion
      rate of normal glucose tolerance than that in the control group (chi 2 = 8.31, P
      < 0.01). CONCLUSION: TCM intervention is possibly effective in delaying the
      conversion of IGT to DM type 2, and plays integrative effeciency in impelling IGT
      patients to health. The favorable education and treatment of DM controlling,
      including dieto- and kineto-therapy may also be advantageous in IGT intervention,
      but could not be effective in blocking the advance of IGT.

PMID- 15143716
TI  - [Effect of Radix notoginseng saponins on platelet activating molecule expression
      and aggregation in patients with blood hyperviscosity syndrome].
AB  - OBJECTIVE: In order to explore the relationship between the active components and
      the functional links of Chinese herbs, the effect of Xuesaitong capsule, a
      preparation made of multi-component Panax notoginseng saponins (PNS) on platelet
      activating molecule expression and aggregation in patients with blood
      hyperviscosity syndrome (BHS) was observed, with aspirin (ASP) as a control.
      METHODS: One hundred and twenty patients with BHS were divided, adopting
      randomized, double-blinded and double simulated principle into 2 groups, the PNS
      group and the ASP group, 60 in each group. Changes of the TCM clinical syndrome,
      platelet adhesion and aggregation, endothelin (ET), prostacyclin, thromboxane,
      CD62P and CD41 before treatment and after 28 days treatment were observed.
      RESULTS: Comparison between the therapeutic effects of the two groups on TCM
      clinical syndrome showed that the total effective rate in the PNS group was
      86.67% and that in the ASP group 56.67%, showing significant difference (P <
      0.05). Compared with before treatment, after treatment, levels of platelet
      adhesion and aggregation, endothelin, prostacyclin and thromboxane were
      significantly different in both groups (P < 0.05 or P < 0.01); levels of CD62P
      and CD41 in the PNS group were also significantly different, but the difference
      was insignificant in the ASP group; no significant difference was shown in both
      groups in levels of triglyceride, total cholesterol and very low density
      lipoprotein-cholesterol. CONCLUSION: PNS may inhibit activation of platelet
      through multiple components and multiple pathways, which is different from that
      of ASP, only through inhibition on arachidonic acid metabolism to suppress
      platelet aggregation. PNS has effects of decreasing platelet superficial
      activation, inhibiting platelet adhesion and aggregation, preventing thrombosis
      and improving microcirculation, and its therapeutic effect on clinical syndrome
      is better than that of ASP.

PMID- 15143718
TI  - [Clinical observation on treatment of SARS with combination of chaihu droplet
      pill and huoxiang zhengqi droplet pill].
AB  - OBJECTIVE: To observe the effect of combination treatment with Chaihu Droplet
      pill (CHDP) and Huoxiang Zhengqi Droplet pill (HZDP) in treating severe acute
      respiratory syndrome (SARS) in early stage. METHODS: Twenty-two patients of SARS
      were randomly selected and paired according to such controlling factors as age,
      sex and profession into 11 couples. To them all symptomatic treatment was
      applied, combined CHDP and HZDP (CH-HZ) was given additionally to one of each
      couple randomly. The treatment was lasted for 13 days to investigate the changes
      of the clinical indexes such as creatine kinase (CK), lactate dehydogenase (LDH)
      and serum sodium levels. RESULTS: Early applying of CH-HZ treatment showed good
      effects in improving CK, LDH, oxygenation index and absolute value of
      neutrophils, and could reduce the daily maximal dosage of glucocorticoid needed
      for SARS patients. CONCLUSION: Early application of CH-HZ treatment in treating
      SARS could alleviate the injury in lung of SARS patients and the neutrophil
      dependent inflammatory reaction, and reduce the dosage of glucocorticoid used.

PMID- 15143720
TI  - [Effect of xiongshao capsule on vascular remodeling in rabbit with experimental
      atherosclerosis].
AB  - OBJECTIVE: To study the effect of Xiongshao Capsule (XSC) on vascular remodeling
      in experimental atherosclerotic (AS) rabbits, and to explore the possible
      mechanisms. METHODS: Rabbit's fractional AS model was established by denuding and
      injuring the abdominal artery with 4F.Fogarty catheter, and followed with high
      cholesterol feeding. The animals were randomly divided into 8 groups, namely, the
      modeled group of 3 days, 2 weeks and 6 weeks after balloon injury (A, B and C);
      the single endothelium injury group (D), the probucol treating group (E), the low
      dose and high-dose XSC treating group (F and G) and the normal control group (N).
      Except the rabbits in Group N and D, the other groups were all fed with high fat
      forage. Histopathological examination of abdominal aorta with the most obvious
      lesion was performed, and the changes of related vascular remodeling indexes
      after arterial injury were observed using computerized image analyzing system;
      the correlation analysis between progress of intimal proliferation and vascular
      remodeling were performed as well. RESULTS: Artery intimal proliferation
      progressed gradually as time went on, which was more significant in Group C as
      compared with that in Group B and D (P < 0.01). All the drugs could reduce the
      maximum intima thickness (MIT). Moreover, both high-dose XSC and Probucol
      profoundly decreased the intima area (IA), showing significant difference as
      compared with that in Group C (P < 0.01). The internal elastic laminal area
      (IELa), external elastic laminal area (EELa), minimum lumen diameter (MLD) and
      lumen area (LA) in Group A increased significantly, as compared with that in
      Group N (P < 0.01). At 6 weeks after balloon injury, with the further intimal
      thickening, IELa, EELa reduced contrarily, resulting in insufficient vascular
      compensation, lumen stricture and MLD reduction (P < 0.01). Improvement of MLD
      and LA was shown in all the drug treated groups, with significant difference in
      comparing with those in Group C (P < 0.01). CONCLUSION: Single endothelium injury
      may be one of the initiating elements of pathological vascular remodeling, which
      could be intensified by hyperlipemia. Intimal proliferation and vascular
      remodeling jointly participated in the pathological course of AS lumen stricture
      after endothelium injury. XSC plays its action in preventing and treating AS
      through inhibiting intimal proliferation after balloon injury and intervening
      pathological vascular remodeling.

PMID- 15143719
TI  - [Study on effect and mechanism of liuwei dihuang decoction in modulating
      hypothalamus-pituitary-ovary axis in senescence accelerated mice model].
AB  - OBJECTIVE: To study the changes of hypothalamus-pituitary-ovary (HPO) axis of
      senescence accelerated mice (SAM) model in their aging process and the modulatory
      effect of Liuwei Dihuang decoction (LW) on the changes. METHODS: Using vaginal
      smear to test the estrous cycle of animal; using radioimmunoassay to determine
      serum levels of estradiol (E2), and beta-endorphin (beta-EP) and substance P (SP)
      in hypothalamus; and the western bloting technique was adopted to quantify the
      level of luteinizing hormone (LH) in pituitary and estradiol receptor alpha (ER
      alpha) in pituitary and ovary. RESULTS: The estrous cycle and diestrus were
      significantly prolonged as SAMP8 aged, the concentration of serum E2 was lower,
      pituitary LH was higher in the SAMP8 than those in SAMR1. Content of beta-Ep and
      SP in hypothalamus gradually lowered during aging, SP content lowered after a
      transient increasing, and ER alpha expression lowered significantly. LW could
      significantly shorten the diestrus, increase weight of ovary, elevate serum E2
      level, significantly reduce the LH level in pituitary, increase beta-EP content
      in hypothalamus and ER alpha expression in ovary, but significantly lower SP
      content in hypothalamus. Oral administration of estrogen could increase serum E2,
      beta-EP and SP content in hypothalamus and ER alpha expression in pituitary, but
      lower LH level in pituitary, weight of ovary and ER alpha level in ovary.
      CONCLUSION: SAMP8, in the aging process, develops a progressive HPO axis
      functional disturbance, it is closely related with the change of levels of
      peptide neuro-mediator in hypothalamus and change of ER alpha level in ovary. LW
      could improve or modulate the HPO axis functional disturbance in SAMP8.

PMID- 15143721
TI  - [Effect of guizhi decoction on CD4+, CD8+ T-lymphocytes and SIgA in mucosal
      immune system in intestine of mice with Bi syndrome (collagen induced immune
      arthritis)].
AB  - OBJECTIVE: To observe the effect of Guizhi Decoction (GZD) on immunological
      indexes in intestinal mucosal immune system of mice with Bi syndrome (collagen
      induced immune arthritis). METHODS: Eighty male DBA mice were randomly divided
      into 4 groups, the normal group, the model group and the high and low dosage GZD
      groups. Model of Bi syndrome was induced by collagen type II. CD4+, CD8+ T
      lymphocytes and SIgA in mice' small intestine and PP node were labeled by
      immunohistochemical staining and their number was calculated using imaging
      analyzer. RESULTS: Compared with the normal group, in the model group, after
      immunization with collagen type II, numbers of CD4+ and CD8+ T-lymphocytes and
      SIgA in mice' intestinal mucosal immune system reduced significantly (P < 0.05 or
      P < 0.01). After treatment with GZD of both high and low dosage, CD4+ T
      lymphocytes and SIgA increased significantly, but significant difference only
      showed in comparison between the high dosage GZD group and the model group (P <
      0.05 or P < 0.01). CONCLUSION: GZD could enhance the immune function in
      intestinal mucosa in mice with Bi syndrome, thus it might induce immune tolerance
      and immune inhibition.

PMID- 15143722
TI  - [Antagonistic effect of baicalin on oxidative stress injury in neurons and
      astrocytes of rats].
AB  - OBJECTIVE: To explore the experimental conditions for H2O2 to injure astrocytes
      and the effect of baicalin in protecting neurons and astrocytes from oxidative
      stress injury. METHODS: Neurons and astrocytes from forebrain of rats were
      cultured in vitro and treated with H2O2, baicalin and combination of the two,
      respectively. The cell viability or survival rate was determined using MTT.
      RESULTS: Effects of H2O2 in different concentrations on survival rate of
      astrocytes showed significant difference (F = 28.569, P < 0.01) in a dose
      dependent manner. Degrees of H2O2 injury, with the same concentration of H2O2, on
      cells with different seeding density were also significantly different (F =
      5.439, P < 0.01), and dose-dependently. Baicalin didn't influence the survival
      rate of neurons and astrocytes when the concentration was within 2.5-40 mumol/L
      (for neurons, F = 0.49, P > 0.05; for astrocytes, F = 1.001, P > 0.05), but
      baicalin showed significant antagonism to the injury of oxidative stress (for
      neurons, F = 24.384, P < 0.01; for astrocytes, F = 5.000, P < 0.01). The higher
      the concentration of bainalin, the higher the cell survival rate. CONCLUSION: A
      model of astrocytes oxidative injury induced by H2O2 is established. Baicalin
      shows no toxicity on neurons and astrocytes when the concentration is within 2.5
      40 mumol/L, but could antagonize the H2O2 caused oxidative injury on cells in a
      dose-dependent manner.

PMID- 15143723
TI  - [Experimental study on inhibitory effect of langchuangjing granule on lupoid
      change of kidney in lupus-prone mice].
AB  - OBJECTIVE: To study the effect and mechanism of Langchuangjing Granule (LCJ) in
      inhibiting the lupoid change of kidney in lupus-prone mice. METHODS: Intervention
      therapy was applied to three group of BW female mice of lupus, 3 months in age,
      for 6-12 weeks with LCJ, prednisone and LCJ + prednisone respectively to observe
      the dynamic development of disease, changes of CD4+, CD8+ and CD54 expression,
      and the effect on pathology of renal corpuscles. RESULTS: Both western and
      Chinese medicines can partially improve the symptoms and plasma CD4+ and CD8+
      distribution, inhibit the increase of serum ICAM-1 content and the high
      expression of CD54 in surface of lymphocyte of peripheral blood, suppress the
      atrophy of renal corpuscles and the proliferation of mesangial cell. The optimal
      effect was showed by the combination of LCJ and prednisone. CONCLUSION: LCJ could
      effectively control and improve the genesis and development of lupoid changes in
      model mice, and regulate the cellular immune function, inhibit the excessive
      immune reaction, and improve the pathology of lupoid nephritis, it could
      cooperate with western medicine to give full play of its effective role and show
      the superiority in treatment.

PMID- 15143724
TI  - [Effect of sanhuang jiangtang recipe on renin-angiotensin system in local
      myocardium in diabetic rats].
AB  - OBJECTIVE: To study the effect of Sanhuang Jiangtang recipe (SJR) on renin
      angiotensin system in local myocardium in diabetic rats. METHODS: Rats were made
      into diabetes model by intraperitoneally administering of streptozocin, and
      medicated through gastrogavage with SJR (50 g/kg), gliclazide (20 mg/kg),
      captopril (15 mg/kg) and nitrendipine (30 mg/kg) respectively, for successive 8
      weeks, started from 2 weeks after modeling. Levels of fasting blood sugar (FBS),
      serum insulin (Ins), heart/body weight ratio (H/BW), myocardial angiotensin II
      (Ang II), angiotensin converting enzyme (ACE) and aldosterone (ALD) were
      determined. And the mRNA expression of type I angiotensin receptor (AT1R) in
      myocardium were detected by RT-PCR assay. RESULTS: As compared with those in the
      normal rats, levels of FBS, H/BW, Ang II, ACE, ALD and AT1R mRNA expression were
      higher (all P < 0.05) and level of serum Ins was lower (P < 0.01) in the model
      rats. SJR, gliclazide, captopril and nitrendipine could slightly reduce the blood
      sugar level in model rats, but with no increase of serum Ins. All the four drugs
      could reduce H/BW, Ang II, ACE and AT1R mRNA expression. SJR and captopril could
      also decrease the ALD content in myocardium. CONCLUSION: Cardiac hypertrophy has
      been induced in 10 weeks after diabetic modeling. Activation of local myocardial
      RAS is related to the genesis of diabetic cardiomyopathy. SJR, gliclazide,
      captopril and nitrendipine could antagonize the genesis of diabetic
      cardiomyopathy, the mechanism is related to the inhibition of RAS activation in
      local myocardium.

PMID- 15143725
TI  - [Clinical study on treatment of allergic rhinitis by yiqi qufeng decoction
      combined with pulverization and acupoint sticking].

PMID- 15143726
TI  - [Clinical observation on effect of modified dachengqi decoction in auxiliary
      treating infantile gastrointestinal disturbance].

PMID- 15143727
TI  - [Effect of yangxue qingnao granule on microcirculation and cerebral blood flow in
      patients with migraine].

PMID- 15143728
TI  - [Standardized clinical research is the key for joining of Chinese medicine into
      mainstream medicine].

PMID- 15143729
TI  - [Current status and direction of researches on antagonizing chemical agents
      induced vomiting by Chinese and Western medicines].

PMID- 15143733
TI  - [Some ideals on higher educational course setting of integrated Chinese and
      Western medicine].

PMID- 15143731
TI  - [Application of Chinese herbal medicine in organ preservative fluid].

PMID- 15143732
TI  - [Generality of sera-pharmacologic experimental study on effect of Chinese herbal
      medicine on liver stellate cells].

PMID- 15143734
TI  - [Minute of 2nd China-Japan-Korea Academic Conference on Blood Stasis Syndrome and
      on Activating Blood Circulation to Remove Stasis].

PMID- 15143739
TI  - [Ascensia CONFIRM: a glycemia monitor known again by patients].

PMID- 15143737
TI  - Implementation of the 'three Rs' in biomedical research.
AB  - A systematic sample of 2800 articles published between 1970 and 2000 in 14 major
      biomedical journals was analysed to assess the implementation of the 'Three Rs'
      (replacement, reduction and refinement) in biomedical research. During this
      period the total number of articles published annually by the journals more than
      doubled, but the proportion of studies using animals decreased by 30 per cent.
      There was a significant increase, from 21 per cent to 35 per cent, in the
      proportion of animal studies which made use of untreated euthanased animals as
      donors of biological materials, a gradual decrease in the number of chronic
      studies on animals, and a 50 per cent decrease in the average number of animals
      used per published paper. There was an improvement in the reporting of the
      specification of the animals' husbandry, conditions of care and environment.
      Parameters of importance for the evaluation of the scientific quality of the
      research and the welfare of the animals were generally poorly reported, but the
      proportion of papers with adequate information on most of the parameters analysed
      increased between 1970 and 2000.

PMID- 15143738
TI  - When things go wrong: managing crisis. A talk with Harry M. Jansen Kraemer, Jr.,
      and Sally Benjamin Young. Interview by Thomasine Kushner.

PMID- 15143735
TI  - Rickettsial spotted fever in Kerala.

PMID- 15143740
TI  - Antischistosomal effects of praziquantel, its alkaline hydrolysis and sun
      decomposed products on experimentally S. mansoni infected albino mice. (A)
      Efficacy assessment based on clinicopathological findings.
AB  - The antischistosomal activity of praziquantel (PZQ), its alkaline hydrolysis
      product (HP) and its sun-decomposed (SD) products was investigated in S. mansoni
      experimentally infected mice. The evaluation was made depending on the degree of
      clinico-pathological changes. The results obtained revealed that, PZQ, HP and the
      SD have induced partial suppression of worm fecundity as judged by the
      significant reduction in eggs per gram of faeces in comparison with the infected
      untreated control. The effect on tissue egg deposition in the treated groups was
      comparable to the infection of untrea ted control. Worm recovery showed large
      reduction in the number of worms for SD (47.6%) and HP (28.6%) compared to PZQ
      (16.6%) treated groups. So, the former two compounds have the superior
      antischistosomal activities. Glutamate pyruvate transominase (GPT) and glutamate
      oxaloacetate transaminase (GOT) concentrations were measured. The GOT values for
      all treated groups were significantly higher than those for the healthy control
      group (p=0.01). The SD group enzyme concentration was even higher than the
      infected untreated control. The GPT values of all groups were greater than the
      uninfected control and the difference was significant for the infected untreated,
      PZQ and the SD treated groups (p=0.05).

PMID- 15143741
TI  - Impact of worktime arrangements on work-home interference among Dutch employees.
AB  - OBJECTIVES: This study examined the effects of different worktime arrangements on
      work-home interference while taking into account other work-related factors,
      private situation and health status, explored gender differences in this
      relation, and examined reciprocal effects between workhours and work-home
      interference. METHODS: Data from the Maastricht cohort study on fatigue at work
      were used with 8 months of follow-up (N=6947 at baseline). RESULTS: Worktime
      arrangements were related to work-home interference among the men and women, even
      after control for confounding. As compared with daywork, baseline shiftwork was
      associated with higher work-home interference over time. Within daywork, full
      time work was prospectively related to higher work-home interference than part
      time work was. For full-timers, baseline overtime work, hours of overtime work,
      change in number of workhours, and commuting time were related to higher work
      home interference over time, whereas compensation for overtime work, familiarity
      with work roster, ability to take a day off, and a decrease in workhours at own
      request were associated with less work-home interference. For the part-timers,
      baseline overtime work and commuting time were related to higher work-home
      interference over time, whereas compensation for overtime, flexible workhours,
      and ability to take a day off were protective against work-home interference.
      Reciprocal relations between work-home interference and workhours were also
      found. CONCLUSIONS: Worktime arrangements are clearly related to work-home
      interference. Because reciprocal effects exist as well, important selection
      processes may exist. Nevertheless, specific characteristics of worktime
      arrangements could constitute useful tools for reducing work-home interference.

PMID- 15143736
TI  - Rhodotorula mucilaginosa, a carotenoid producing yeast strain from a Patagonian
      high-altitude lake.
AB  - The red yeast Rhodotorula mucilaginosa strain CRUB 0138 (previously identified as
      R. lactosa) was isolated from a high-altitude Patagonian Lake Toncek (1700 m
      a.s.l.), and assigned with mucilaginosa species. Its biochemical, physiological
      and molecular features were assessed and compared to R. mucilaginosa PYCC 5166
      type strain using a polyphasic approach; in addition, biomass and carotenoid
      pigment production at different C/N ratios were determined in an incubator
      shaker. Phenetic characterization by means of 70 current physiological tests
      including assimilation of aldaric acids and aromatic compounds, and also the
      ability to grow with amino acids as sole carbon sources, was carried out.
      According to numerical taxonomy calculations, similarity indexes between R.
      mucilaginosa CRUB 0138 and PYCC 5166 type strain were 0.86 and 0.77,
      corresponding to a complete set of physiological tests and MSP-PCR (Mini/Micro
      Satellite Primed PCR; (GTG)5, M13 and (GAC)5 primers were employed)
      fingerprinting. Killer activity against 2 native strains, Rhodosporidium
      kratochvilovae and R. mucilaginosa was detected. Maximum biomass-glucose
      conversion efficiency (87%) and maximum carotenoid yield (2.32 mg/L) were
      obtained at C/N = 5 in culture medium containing 10 and 40 g/L glucose,
      respectively. Different C/N ratios did not influence carotenoid pigment
      production but low C/N enhanced biomass yield.

PMID- 15143742
TI  - Direction of shift rotation among three-shift workers in relation to
      psychological health and work-family conflict.
AB  - OBJECTIVES: The aim of the present study was to investigate whether the direction
      of shift rotation was related to the need for recovery, fatigue, sleep quality,
      work-family conflict, and leisure time among three-shift workers. METHODS: Data
      of 95 workers in forward-rotating three-shift work and 681 workers in backward
      rotating three-shift work, with 32 months of follow-up, in the Maastricht cohort
      study (N=12,095) were used. Both cross-sectional and longitudinal analyses were
      carried out. RESULTS: A backward rotation schedule was prospectively related to
      an increased need for recovery [relative risk (RR) 2.88, 95% confidence interval
      (95% CI) 1.06-7.81] and poor general health (RR 3.21, 95% CI 1.32-7.83), as
      compared with a forward rotation schedule. Adjustment for demographic and health
      variables and the characteristics of the work environment did not alter these
      relations considerably. Furthermore, a forward rotation schedule was
      prospectively related to less work-family conflict and better sleep quality over
      the 32 months of follow-up. Finally, high levels of fatigue, need for recovery,
      poor sleep quality, poor general health, insufficient leisure time, and work
      family conflict at first measurement were associated with an increased risk of
      leaving shiftwork during the follow-up. CONCLUSIONS: Optimization of shiftwork
      schedules, in terms of shift rotation, seems a promising method for decreasing
      the negative impact accompanying shiftwork. Future studies should investigate
      whether these findings for three-shift workers are applicable to other shiftwork
      schedules as well. Furthermore, this study clearly illustrates the existence of
      secondary selection processes among shiftworkers and thereby emphasizes the
      complexity of valid shiftwork research.

PMID- 15143743
TI  - Factors affecting the herd level of antibodies against Mycobacterium avium
      subspecies paratuberculosis in dairy cattle.
AB  - A case-control study was made of Norwegian dairy herds with high and low herd
      levels of antibodies against Mycobacterium avium subspecies paratuberculosis. A
      high proportion of the herds had a considerable number of seropositive cows, and
      environmental and management factors were examined for possible associations with
      the high serological levels of antibodies. The most important appeared to be:
      geographical location, red deer (Cervus elaphus) gaining access to the pastures
      for cattle, the observation of wild birds in the feed storage, and herds sharing
      common pasture with other herds of cattle. However, diagnostic tests showed that
      none of the animals in the case herds was infected with M a paratuberculosis.

PMID- 15143744
TI  - Intrapsychic change: methodological problems in psychotherapy research. 1961.

PMID- 15143745
TI  - Kurt Wuthrich: biographical note.

PMID- 15143746
TI  - NMR studies of structure and function of biological macromolecules (Nobel
      Lecture).

PMID- 15143730
TI  - [Different application of various translation manipulations in translation of
      Chinese medical literatures].

PMID- 15143750
TI  - UK guidelines offer better support for cancer patients.

PMID- 15143749
TI  - The issue of complementarity.

PMID- 15143747
TI  - Non-specific bronchial hyperresponsiveness is a risk factor for steroid
      insensitivity in nasal polyposis.
AB  - OBJECTIVE: Management of nasal polyposis should be primarily medical. Resorting
      to intranasal ethmoidectomy should not be envisaged before a trial of dual
      steroid therapy. Nevertheless, no risk factor for steroid insensitivity in
      patients with nasal polyposis is actually defined. The aim of this study is to
      evaluate whether the presence of asthma and/or non-specific bronchial
      hyperresponsiveness (BHR) can be considered a risk factor for steroid
      insensitivity. MATERIAL AND METHODS: This study focused on the evaluation of a
      dual modality, topical and systemic, over a follow-up period of 3 years. A total
      of 55 subjects with and 45 subjects without BHR were treated according to a
      standardized therapeutic protocol combining short-term oral administration of
      prednisolone and a daily intranasal spray of beclomethasone. RESULTS: Over the
      follow-up period of 3 years, this dual modality proved to be successful in 93.4%
      of subjects without BHR and without aspirin idiosyncrasy, in 82.2% of subjects
      with BHR and without aspirin idiosyncrasy and in 60% of subjects with BHR and
      aspirin idiosyncrasy. The percentage of patients who underwent surgery after the
      failure of medical treatment was significantly larger in patients with than
      without BHR (p < 0.05) and in patients with than without aspirin idiosyncrasy (p
      < 0.02). CONCLUSION: The presence of BHR and/or aspirin idiosyncrasy can be
      considered a major risk factor for steroid insensitivity in patients with nasal
      polyposis.

PMID- 15143751
TI  - Tobacco fights back.

PMID- 15143752
TI  - The Universities of the Renaissance and Reformation.
AB  - European universities had great intellectual and religious influence in the
      Renaissance and Reformation and exhibited considerable variety. Italian
      universities taught law and medicine to doctoral students. Their loose
      organization made it possible for professors to produce original research in law,
      medicine, philosophy, and the humanities. Northern European universities
      concentrated on teaching arts to undergraduates, while theology was the most
      important graduate faculty. Their stronger structure enabled Martin Luther and
      other professors of theology in German, Dutch, Swiss, and English universities to
      create and lead the Protestant. By the early seventeenth century universities
      everywhere were in decline.

PMID- 15143753
TI  - Truths and consequences: writing the history of disease. [Review of: Gerald N.
      Grob. The Deadly truth: A history of disease in America. Cambridge, Mass, Harvard
      University Press, 2002].

PMID- 15143756
TI  - [Current trends and issues of the Japanese pharmaceutical industry].

PMID- 15143754
TI  - Working and knowing in the history of STM. [Review of: Pickstone, John V. Ways of
      knowing. A new history of science, technology and medicine. Manchester,
      Manchester University Press, 2000].

PMID- 15143755
TI  - [The separation of drug dispensaries from medical practice in the Taisho era; the
      intense conflict between pharmacists and medical doctors].

PMID- 15143757
TI  - [A study on formulas of Ettyu-Hangontan during the Edo period].
AB  - Since 1640, Borneol was brought to Nagasaki from South-East Asia by the Dutch
      ships. As a result, it was introduced as a component unique to "Hangontan" which
      was distributed by the pill-peddler of Toyama during the Edo period. We intend to
      discuss how to bring about such a formula for the "Hangontan" of Toyama.

PMID- 15143748
TI  - Perspectives: the third revolution in health.

PMID- 15143759
TI  - The historical documentation of scientific developments: scientists should
      participate.

PMID- 15143758
TI  - Nobel Prizes for nuclear magnetic resonance imaging: 2003 and historical
      perspectives.

PMID- 15143761
TI  - [Examination of the Tanyin chapter of the "Heji Jufang"].
AB  - An examination of the tanyin chapter of the "Heji Jufang", the world's first
      national pharmacopoeia and the major pharmacopoeia of the Northern Sung era,
      yielded the following findings:(1) In the tanyin chapter, we identified many
      examples of discussions based on the theory of "lung and stomach disorders".
      Since this theoryis not found in medical books before the Tang era, and since
      many examples can be found in the "Heji Jufang" and other medical books of the
      same period, we believe this is a view of pathology peculiar to the Northern Sung
      era.(2) A comparison of the components of prescriptions used in the "Waitai
      Miyaofang" and the tanyin chapter of the "Heji Jufang" revealed that the former
      contains many strong diuretics, purgatives, and crude drugs of a hot nature,
      while the later contains few of these but many diuretics that have a mild
      antitussive effect. We believe the use of medicines in the latter is related to
      the treatment of "avoiding diuretics and purgatives which could adversely affect
      pi qi."(3) We pointed out that the er chen tang in the tanyin chapter of the
      "Heji Jufang" is merely one prescription of a group of prescriptions to treat a
      morbid condition caused by the disorders of the stagnant tanyin. We revealed in
      the "Yijianfang" and "Wangbing Huichun" the process by which, with the passage of
      time, that er chen tang came to be widely interpreted as the basic prescription
      for tanyin, including chronic cases.

PMID- 15143762
TI  - [Clinical images in gastroenterology. Trichobezoar and perforated gastric ulcer].

PMID- 15143764
TI  - [Reversible hearing loss in acute salicylate intoxication].
AB  - Acetylic acid, such as aspirin, is one of the most commonly used medication in
      Western societies. Aspirin overdosage causes ototoxic side effects in some
      patients, such as bilateral mild to moderate sensorineural hearing loss and
      tinnitus. Recent literature describes, that salicylates act as competitive
      inhibitors of Cl- anions at the anion-binding site of prestin, the motor protein
      of the outer hair cell. This molecular mechanism correlates well with the
      clinical audiological mainstays of aspirin-induced hearing loss, dose dependency,
      cochlear site of hearing loss and reversibility. We report about a young man with
      an acute moderate aspirin intoxication resulting in asymmetric hearing loss of 50
      dB HL and tinnitus for five days. Otoacoustic emissions were absent on the first
      day of intoxication but could be measured again on the fifth day after the
      intoxication. As the ototoxic side effects resolve with in two or three days, no
      specific treatment is necessary for ototoxicity. Medical treatment of acute or
      chronic aspirin intoxications aims to decrease further drug absorption by
      gastrointestinal decontamination and to accelerate elimination by alkaline
      diuresis. Only in severe intoxications hemodialysis may be considered to treat
      neurologic, pulmonal, renal or cardial complications.

PMID- 15143763
TI  - [Hearing aids in the elderly. Why is the accommodation so difficult?].
AB  - PRELIMINARY REMARKS: The acceptance of hearing-aids by elderly people is
      generally poor. Hearing loss on the other hand increases with age, and the
      ability to communicate,especially in random noise, diminishes. PATIENTS AND
      METHODS: Audiometric data on 331 individuals older than 60 years were collected.
      Sixty people between 15 and 30 and 86 people between 31 and 60 years acted as
      controls. Tympanograms, hearing thresholds, speech audiometry and dichotic
      hearing as well as binaural masking level differences and otoacustic emissions
      for eight frequencies were measured. Hearing aid status was also determined.
      RESULTS: Our data show more hearing deficits at low frequencies as indicated in
      the literature. Presbycusis is present solely in the internal ear in 11.5-27.7%,
      in central hearing structures in 3.8-21.4%, but mainly in all parts of the
      auditory pathway 50.9-84.6% of cases. Only 15.3% of patients needing hearing aids
      were actually provided with them. CONCLUSION: Hearing decreases with age but some
      older people have completely normal hearing. Therefore, a physiological
      presbycusis does not exist. There are deficits in the inner ear as well as in the
      central auditory structures which should be determined by audiometric diagnosis.
      Hearing aid supply should be carefully regulated and audiotherapy carried out.

PMID- 15143765
TI  - [Current developments in cochlear implantation].
AB  - Over the last 20 years, cochlear implantation has become a well accepted
      treatment in patients suffering from hearing loss or congenital deafness. Results
      have been impressive,and indications for a cochlear implant have been extended
      continuously. Thanks to a sophisticated diagnostic procedure, optimization of the
      surgical technique, and the progression of interdisciplinary cooperation in the
      field of rehabilitation, the acceptance of cochlear implantation is growing
      significantly. The manufacturers of the devices are making great efforts to
      miniaturize the external components of the system, and new developments in
      electrode arrays, combined with new speech coding strategies, result in better
      speech understanding. The new developments in electrode design, however, are not
      necessarily improvements over recent years. Nevertheless, a very well functioning
      network of physicians, scientists, and manufacturers has acted and reacted in an
      outstanding manner to identify possible causes of post-implantation meningitis,
      have taken immediate counter measures and presented possibilities of prevention.

PMID- 15143760
TI  - Significant events in the developments of MRI.

PMID- 15143766
TI  - Photonics: tuning holes in photonic-crystal nanocavities.
AB  - One challenge in photonics is strongly to confine light in small volumes in order
      to increase light-matter interaction. Akahane et al. propose a new concept for
      increasing the lifetime of this interaction, based on tailoring of the Fourier
      spectrum of cavity modes, which they believe is demonstrated by the surprising
      enhancement (roughly tenfold) of the quality factor Q of the cavity as a result
      of fine-tuning the mirror-hole geometry in a photonic-crystal nanocavity. Here we
      question the validity of their concept and argue that the improvement in Q is due
      to an increase in the impedance wave matching at the cavity edges and to a slow
      wave effect. This alternative interpretation opens the way to new cavity designs.

PMID- 15143768
TI  - [The history of the development and changes of quinolone antibacterial agents].
AB  - The quinolones, especially the new quinolones (the 6-fluoroquinolones), are the
      synthetic antibacterial agents to rival the Beta-lactam and the macrolide
      antibacterials for impact in clinical usage in the antibacterial therapeutic
      field. They have a broad antibacterial spectrum of activity against Gram
      positive, Gram-negative and mycobacterial pathogens as well as anaerobes.
      Further, they show good-to-moderate oral absorption and tissue penetration with
      favorable pharmacokinetics in humans resulting in high clinical efficacy in the
      treatment of many kinds of infections. They also exhibit excellent safety
      profiles as well as those of oral Beta-lactam antibiotics. The bacterial effects
      of quinolones inhibit the function of bacterial DNA gyrase and topoisomerase IV.
      The history of the development of the quinolones originated from nalidixic acid
      (NA), developed in 1962. In addition, the breakthrough in the drug design for the
      scaffold and the basic side chains have allowed improvements to be made to the
      first new quinolone, norfloxacin (NFLX), patented in 1978. Although currently
      more than 10,000 compounds have been already synthesized in the world, only two
      percent of them were developed and tested in clinical studies. Furthermore, out
      of all these compounds, only twenty have been successfully launched into the
      market. In this paper, the history of the development and changes of the
      quinolones are described from the first quinolone, NA, via, the first new
      quinolone (6-fluorinated quinolone) NFLX, to the latest extended-spectrum
      quinolone antibacterial agents against multi-drug resistant bacterial infections.
      NA has only modest activity against Gram-negative bacteria and low oral
      absorption, therefore a suitable candidate for treatment of systemic infections
      (UTIs) is required. Since the original discovery of NA, a series of quinolones,
      which are referred to as the old quinolones, have been developed leading to the
      first new quinolone, NFLX, with moderate improvements in over all properties
      starting in 1962 through and continuing throughout the 1970's. Especially, the
      drug design for pipemidic acid (PPA) indicated one of the important breakthroughs
      that lead to NFLX. The introduction of a piperazinyl group, which ia a basic
      moiety at the C7-position of the quinolone nuclei, improved activity against Gram
      negative organisms broadening the spectrum to include Pseudomonas aeruginosa. PPA
      also showed soem activity against Gram-positive bac teria. The basic piperazine
      ring, which can form the zwitterionic natrure with the carboxylic acid at the C3
      position, has subsequently been shown to increase the ability of the drugs to
      penetrate the bacterial cells resulting in enhanced activity. Further, the
      zwitterionic forms resulted in significant tissue penetration in the
      pharmacokinetics. On the other hand, the first compound with a fluorine atom at
      the C6-position of the related quinolone scaffold was flumequine and the compound
      indicated that activity against Gram-positive bacteria could be improved in the
      old quinolones. The addition of a flourine atom at the C6-position is essential
      for the inhibition of target enzymes. The results show the poten antibacterial
      activity and the penetration of the quinolone molecule into the bacterial cells
      and human tissue. The real breakthrough came with the combination of these two
      features in NFLX, a 6-fluorinated quinolone having a piperazinyl group at the C7
      position, NFLX features significant differences from the old quinolones in the
      activities and pharmacokinetics in humans, resulting in high clinical efficacy in
      the treatment of many kinds of infections including RTIs.Consequently, those
      great discoveries are rapidly superseded by even better compounds and NFLX proved
      to be just the beginning of a highly successful period of research into the
      modifications of the new quinolone antibacterials. Simce the chemical structure
      and important features of NFLX had become apparent in 1978, many compounds were
      patented in the next three years, several of which reached the market. Among the
      drugs, ofloxacin (OFLX) and ciprofloxacin (CPFX) are recognized as superior in
      several respects to the oral beta-lactam antibiotics as an antibacterial agent.
      With a focus on OFLX and CPFX, numerous research groups entered the antibacterial
      therapeutic field, triggering intense competition in the search to find newer,
      more effective quinolones. After NFLX was introduced in the market, while
      resulting by the end of today, eleven kinds of other new quinolones launched in
      Japan. They are enoxacin (ENX), OFLX, CPFX, lomefloxacin (LFLX), fleroxacin
      (FRLX), tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX),
      gatifloxacin (GFLX), prulifloxacin (PULX) and also pazufloxacin (PZFX). The
      advantages of these compounds, e.g., LVFX, SPFX and GFLX, are that their spectrum
      includes Gram-positive bacteria species as well as Gram-negative bacteria and
      they improve bioavailability results when a daily dose is administered for
      systemic infections including RTIs. However, unexpected adverse reactions, such
      as the CNS reaction, the drug-drug interaction, phototoxicity, hepatotoxicity and
      cardiotoxicity such as the QTc interval prolongation of ECG, have been reported
      in the clinical evaluations or the post-marketing surveillance of several new
      quinolones. Moreover, the adverse reactions of arthropathy (the joint toxicity)
      predicated from studies in juvenile animals have never materialized in clinical
      use. Therefore, no drugs other than NFLX have yet been approved for pediatric
      use. Fortunately, the newer quinolones are being developed and tested to reduce
      these adverse reactions on the basis of recent studies. On the other hand, multi
      drug resistant Gram-positive bacteria including methicillin-resistant
      Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative
      staphycolocci (MRCNS), penicillin-resistant Streptococcus pneumoniae (PRSP) and
      vancomycin-resistant enterococci (VRE) have been a serious problem in the medical
      community. Recently, the new quinolone antibacterials are highly successful class
      of antibacterial therapeutic field, however, the increased isolation of quinolone
      resistant bacteria above them has become a normal outcome. These problems of
      multi-drug resistance have been the driving force for the development of newer
      quinolones. The next gereration of quinolone antibacterial agents will be potent
      against multi-drug resistant bacteria, such as MRSA, and provide a lower rate of
      emergence in resistance. Further, they should have favorable safety profiles to
      reduce the adverse reactions. The future of quinolones as the ultimate in
      pharmaceuticals must be handled cautiously if they are to realize their potential
      in the medical community.

PMID- 15143770
TI  - Omp85, an evolutionarily conserved bacterial protein involved in outer-membrane
      protein assembly.
AB  - The insertion of proteins into membranes generally requires the assistance of
      membrane proteins. A protein, designated Omp85 in Neisseria meningitidis, was
      shown to be required for the assembly of bacterial outer-membrane proteins. The
      protein is essential for the viability of the bacteria and is ubiquitous among
      Gram-negative bacteria. Omp85 depletion results in the accumulation of aggregates
      of unfolded outer-membrane proteins, and we argue that Omp85 is directly involved
      in outer-membrane-protein assembly. Omp85 shows sequence similarity with Toc75 of
      the chloroplast protein-import machinery, suggesting a common evolutionary
      origin.

PMID- 15143769
TI  - Brain involvement in multicentric Epstein-Barr virus-associated smooth muscle
      tumours in a child after kidney transplantation.
AB  - Epstein-Barr virus (EBV)-associated smooth muscle tumours (SMT) have been
      reported in young patients with induced immunosuppression associated with organ
      transplantation, acquired immunodeficiency syndrome or congenital
      immunodeficiencies. EBV-associated SMT are frequently multicentric or multifocal
      and often occur in unusual locations. We are reporting a case of EBV-associated
      multicentric SMT that occurred after kidney transplantation in a 2-year-old boy
      with a history of oligomeganephrony. Headaches and left VIth cranial nerve
      paralysis led to the discovery of a brain tumour 3 years after transplantation.
      There were multiple pulmonary, hepatic and splenic nodules and enlarged
      mesenteric lymph nodes. Histological examination revealed multicentric SMT of
      uncertain malignant potential. Further investigations using in situ hybridisation
      demonstrated EBV early RNAs in the nucleus of most tumour cells. The
      immunosuppressive therapy was reduced, and the child was treated with
      chemotherapy, but died 2 months later, due to neurological complications.

PMID- 15143771
TI  - Somatisation or not?

PMID- 15143767
TI  - [A pair of crude drugs used in Shang-Han-Lun, especially the ways of using
      roasted licorice].
AB  - The frequency and usage of "Yao-dui" (pair of two kinds of crude drugs, Yaku-tai
      used in Shang-Han-Lun, a famous formulary in traditional Chinese medicine, was
      examined. The best ten kinds of pairs of two crude drugs frequently mentioned in
      the formulary were those among five drugs contained in Guizhi-tang (Keishi-to in
      Japanese), which is a major formulation in Shang-Han-Lun. Radix Glycyrrhizae
      Preparata (Sha-kanzo in Japanese) and Ramulus Cinnamomi (Keishi in Japanese) were
      used in pairs very frequently, which is used for the treatment of palpitation
      caused by Xin-yang deficiency (Shin-yo-kyo in Japanese) and usually used with
      Poria. Radix Glycyrrhizae Preparata and Radix Paeoniae worked in pairs for the
      treatment of muscular spasm and pain due to Xue-deficiency-syndrome (Kekkyo in
      Japanese). Radix Glycyrrhizae Preparata is used together with Rhizoma Zingiberis
      (Kankyou in Japanese) for the treatment of diarrhea accompanied with cold pain in
      the lower abdomen and usually used with Radix Ginseng and Aconiti Preparata. The
      experimental knowledge of the usage of these crude drug pairs will be useful to
      create a new formulation of crude drugs for modern medical treatment.

PMID- 15143773
TI  - Stem cell politics get dirty.

PMID- 15143777
TI  - A voluntary patient support service in general practice.

PMID- 15143776
TI  - Cancer statistics digest: mortality trend for "oral cavity and pharynx" and
      "larynx" cancer in Japan: 1960-2000.

PMID- 15143775
TI  - [From psychooncological research to clinical practice].

PMID- 15143774
TI  - Cancer education, prevention and early detection in indigenous population in the
      Isthmus of Tehuantepec, Oaxaca, Mexico: The Cancer Prevention and Research Center
      (CEPREC) Project.

PMID- 15143779
TI  - Editorial for computerized medical imaging and graphics.

PMID- 15143778
TI  - Disability now.

PMID- 15143780
TI  - Statistics--for fun and therapy.

PMID- 15143781
TI  - Springtime in Paris. Evaluating the heathcare system in France.

PMID- 15143772
TI  - Diagnosis of bacterial LRTI.

PMID- 15143784
TI  - Congenital infection with Trypanosoma cruzi: from mechanisms of transmission to
      strategies for diagnosis and control.

PMID- 15143785
TI  - Limitations of an indoor air pollution index.

PMID- 15143788
TI  - Source extraction information from air quality data monitored in an Argentinean
      steel mill.
AB  - A statistical analysis of a series of ambient air concentrations of suspended
      particulate matter (SPM) and NO2 is presented. Measurements were taken at four
      sites that belong to an Argentinean steel mill and in another site located in its
      vicinity. The air pollutants were measured during a three-week exploratory
      sampling. The monitoring sites were selected on the basis of relevant
      characteristics of the emission sources and the corresponding climatological
      statistics of the last decade. Suspended particulate matter with aerodynamic
      diameter of less than 10 microm (PM10) and NO2 were continuously measured at only
      one site, while 1-hr samples of NO2 and 24-hr samples of total SPM and SO2 were
      collected at the other sites. The registered concentrations show that SPM was the
      pollutant of major concern. A first estimate about the nature of the contribution
      of the different sources of particles and NO2 present in the area was obtained
      through the statistical analysis of measured concentration data coupled with
      prevalent meteorological variables.

PMID- 15143791
TI  - Hot emission model for mobile sources: application to the metropolitan region of
      the city of Santiago, Chile.
AB  - Depending on the final application, several methodologies for traffic emission
      estimation have been developed. Emission estimation based on total miles traveled
      or other average factors is a sufficient approach only for extended areas such as
      national or worldwide areas. For road emission control and strategies design,
      microscale analysis based on real-world emission estimations is often required.
      This involves actual driving behavior and emission factors of the local vehicle
      fleet under study. This paper reports on a microscale model for hot road
      emissions and its application to the metropolitan region of the city of Santiago,
      Chile. The methodology considers the street-by-street hot emission estimation
      with its temporal and spatial distribution. The input data come from experimental
      emission factors based on local driving patterns and traffic surveys of traffic
      flows for different vehicle categories. The methodology developed is able to
      estimate hourly hot road CO, total unburned hydrocarbons (THCs), particulate
      matter (PM), and NO(x) emissions for predefined day types and vehicle categories.

PMID- 15143789
TI  - The effect of opening windows on air change rates in two homes.
AB  - More than 300 air change rate experiments were completed in two occupied
      residences: a two-story detached house in Redwood City, CA, and a three-story
      townhouse in Reston, VA. A continuous monitor was used to measure the decay of
      SF6 tracer gas over periods of 1-18 hr. Each experiment first included a
      measurement of the air change rate with all exterior doors and windows closed
      (State 0), then a measurement with the single change from State 0 conditions of
      opening one or more windows. The overall average State 0 air change rate was 0.37
      air changes per hour (hr(-1)) (SD = 0.10 hr(-1); n = 112) for the California
      house and 0.41 hr(-1) (SD = 0.19 hr(-1); n = 203) for the Virginia house.
      Indoor/outdoor temperature differences appeared to be responsible for the
      variation at the Virginia house of 0.15-0.85 hr(-1) when windows were closed.
      Opening a single window increased the State 0 air change rate by an amount
      roughly proportional to the width of the opening, reaching increments as high as
      0.80 hr(-1) in the California house and 1.3 hr(-1) in the Virginia house.
      Multiple window openings increased the air change rate by amounts ranging from
      0.10 to 2.8 hr(-1) in the California house and from 0.49 to 1.7 hr(-1) in the
      Virginia house. Compared with temperature differences and wind effects, opening
      windows produced the greatest increase in the air change rates measured in both
      homes. Results of this study indicate the importance of occupant window-opening
      behavior on a home's air change rate and the consequent need to incorporate this
      factor when estimating human exposure to indoor air pollutants.

PMID- 15143790
TI  - Air intake contamination by building exhausts: tracer gas investigation of
      atmospheric dispersion models in the urban environment.
AB  - The establishment of a safe distance between sources of pollution and air intakes
      is based on a complex exercise that should take into account several wind,
      physical, and topographical factors. To estimate the maximum concentrations of
      the pollutants as a function of the distance from the emission source, some
      heating, ventilation, and air conditioning (HVAC) system designers use the
      atmospheric dispersion models suggested by the American Society of Heating,
      Refrigerating, and Air-Conditioning Engineers (ASHRAE). Two of these models, the
      Halitsky and Wilson-Chui-Lamb models, have been developed and evaluated mainly
      with laboratory data. There have been relatively few evaluations with full-scale
      field data. The objective of this study, carried out on a building in downtown
      Montreal, Quebec, Canada, was to compare the measured concentrations of a tracer
      gas emitted by an exhaust stack with those predicted by these models. The results
      indicate that the Halitsky model gives lower than actual dilution, while the
      Wilson-Chui-Lamb model generally gives acceptable estimates, with occasional over
      estimations of the dilution.

PMID- 15143783
TI  - Obesity--the challenge ahead.

PMID- 15143792
TI  - Spray charging of droplets in a wet scrubber.
AB  - The experimental setup was designed to study the effect of natural charging of
      droplets during spraying (called spray electrification or spray charging) in a
      wet scrubber. The influence of nozzle material, liquid feed rate, and liquid
      composition on the specific charge (charge per unit volume of liquid) formed in
      spraying was measured. It was found that the nozzle material has no measurable
      effect on this specific charge. Increasing the liquid feed rate increases the
      specific charge significantly. Increasing solute (NaCl or NaOH) concentration
      increases the conductivity that decreases the formed specific charge. The same
      correlation between the specific charge and conductivity was also observed with
      real scrubbing liquids. It is proposed that the specific charge depends only on
      the value of liquid conductivity, not on liquid composition. The conductivity of
      the tested scrubbing liquids was high enough to suppress the formation of a high
      specific charge during spraying.

PMID- 15143782
TI  - Evidence-based medicine: a matter of belief.

PMID- 15143794
TI  - Combined simulation of combustion and gas flow in a grate-type incinerator.
AB  - Computational fluid dynamic (CFD) analysis of the thermal flow in the combustion
      chamber of a solid waste incinerator provides crucial insight into the
      incinerator's performance. However, the interrelation of the gas flow with the
      burning waste has not been adequately treated in many CFD models. A strategy for
      a combined simulation of the waste combustion and the gas flow in the furnace is
      introduced here. When coupled with CFD, a model of the waste combustion in the
      bed provides the inlet conditions for the gas flow field and receives the
      radiative heat flux onto the bed from the furnace wall and gaseous species. An
      unsteady one-dimensional bed model was used for the test simulation, in which the
      moving bed was treated as a packed bed of homogeneous fuel particles. The
      simulation results show the physical processes of the waste combustion and its
      interaction with the gas flow for various operational parameters.

PMID- 15143793
TI  - An examination of the 6:00 a.m.-9:00 a.m. measurements of ozone precursors in the
      New York City metropolitan area.
AB  - In recent years, ambient measurements of hourly ozone precursor concentrations,
      namely speciated and total nonmethane organic compounds (NMOCs), have become
      available through the Photochemical Assessment Monitoring Stations (PAMS)
      program. Prior to this, NMOCs were measured in the central business district
      using a canister to obtain the 3-hr integrated sample for the 6:00 a.m.-9:00 a.m.
      period. Such sampling had been carried out annually for nearly a decade at three
      locations in the New York City metropolitan area. The intent of these
      measurements, along with measurements of the other ozone precursor, NO(x), was to
      provide an understanding of ozone formation and the emissions loading and mix in
      the urban area. The analysis of NMOC and NO(x) measurements shows a downward
      trend in the case of NMOC. In addition, we compared the canister-based NMOC
      concentrations with data obtained from the PAMS program for the 6:00 a.m.-9:00
      a.m. period. Analysis of the NMOC concentrations reveals poor spatial correlation
      between the various monitors, reflecting the effect of localized emissions. This
      suggests that NMOC measurements made at a single location cannot be viewed as
      representative of the entire region. On the other hand, correlations were found
      to be higher among the NO(x) monitors, indicating the commonality of emission

PMID- 15143796
TI  - Development and demonstration of an explicit lumped-parameter biofilter model and
      design equation incorporating monod kinetics.
AB  - Biofiltration is an economical air pollution control (APC) technology,
      particularly suitable for the treatment of air-streams having high flow rates and
      low concentrations of volatile organic compounds (VOCs). This technology utilizes
      enzymatic catalysis at ambient conditions to mineralize such pollutants to CO2,
      H2O, and salts. A pilot-scale study conducted for more than 4 years investigated
      the development of a new biofiltration technology employing trickle bed air
      biofilters (TBABs). Following the completion of this experimental study,
      additional data analysis was performed to develop a simple lumped-parameter
      biofilter model, assuming first-order kinetics. This model related the observed
      biofilter performance to the principle independent physical, thermodynamic, and
      biochemical parameters. The initial model has subsequently been expanded to
      incorporate Monod kinetics. In this paper, the development and use of the final
      explicit lumped-parameter biofilter model and design equation, incorporating
      Monod kinetics, are presented. To facilitate the application of this model,
      practical procedures are also presented for the determination of VOC solubility,
      VOC biokinetic Monod parameters, and the maximum practical biofilter inlet VOC
      concentration.

PMID- 15143797
TI  - Real-world vehicle emissions: a summary of the Eleventh Coordinating Research
      Council On-Road Vehicle Emissions Workshop.
AB  - The Coordinating Research Council (CRC) held its eleventh workshop in March 2001,
      focusing on results from the most recent real-world vehicle emissions research.
      We summarize the presentations from researchers engaged in improving our
      understanding of the contribution of mobile sources to ambient air quality and
      emission inventories. Participants in the workshop discussed efforts to improve
      mobile source emission models and emission inventories, the role of on-board
      diagnostic (OBD) systems in inspection and maintenance (I/M) programs,
      particulate matter (PM) emissions, contributions of diesel vehicles to the
      emission inventory, on-road emissions measurements, fuel effects, unregulated
      emissions, and microscale and modal emission models, as well as topics for future
      research.

PMID- 15143786
TI  - Re: A comparison of four gravimetric fine particle sampling methods.

PMID- 15143798
TI  - Effect of solids concentration on bacterial leaching of heavy metals from sewage
      sludge.
AB  - Microbial metal leaching from sewage sludge (2-9% w/v) was carried out with the
      iron-oxidizing bacterium Thiobacillus ferrooxidans. Measurements of pH, oxidation
      reduction potential, and concentration of Fe2+ indicated that T. ferrooxidans was
      effective in removing metals from an incubation bath containing less than 5%
      sludge solids concentration. Specifically, Cu leaching was completely suppressed
      at a high solids concentration of 9% (w/v). Results indicated that the
      deactivation of T. ferrooxidans at a high sludge content was mainly due to the
      presence of inhibiting materials such as organic matter. A mixed culture of
      sulfur-oxidizing bacteria was obtained by enrichment from anaerobically digested
      sewage sludge to enhance the efficiency of the microbial leaching process. These
      bacteria were much more effective in metal leaching than was iron-oxidizing T.
      ferrooxidans. At 9% (w/v) solids concentration, the leaching efficiencies of Zn
      and Cu were 78% (2.66 g/kg dry sludge) and 59% (1.36 g/kg dry sludge),
      respectively. Therefore, when removing heavy metals from the anaerobically
      digested sewage sludge, the indigenous sulfur-oxidizing bacteria isolated in the
      current study were more efficient than T. ferrooxidans, especially at high sludge
      solids concentrations.

PMID- 15143787
TI  - Quantitative analysis of environmental factors in differential weighing of blank
      Teflon filters.
AB  - Mass differences less than 100 microg must be correctly measured in gravimetric
      analysis of particles collected on filters. Even small variations in mass
      measurement may contribute significant errors to calculated concentrations. In
      addition to the collected particles, a number of other factors affect the
      observed mass difference between the measurements before and after sampling. The
      most often controlled of these factors are static charge, temperature, and
      humidity. Using 951 laboratory blank filter weights, we have statistically
      analyzed these and other factors that affect the observed filter weight. Some of
      these are controllable or correctable; others are not and enter into the final
      results as errors. The standard deviation of differential blank filter weighing
      after applying all corrections was 2.7 microg. The most important correctable
      factors are air buoyancy variation and filter storage time. When weighing blank
      Teflon filters at relative humidity < 50%, these are an order of magnitude more
      important than weighing-room humidity. Using field blank filters in each weighing
      batch could control these three factors but also doubles the errors caused by
      balance random variation and filter handling contamination, because four weighing
      measurements and the handling of two filters are needed to obtain one corrected
      differential mass result.

PMID- 15143799
TI  - Theoretical study of selective methylation in the synthesis of azithromycin.
AB  - Azithromycin is a 15-membered macrolide antibiotic which is active in vitro
      against clinically important gram-negative bacteria. In this study, the
      selectivity of the methylation mechanism was analyzed computationally on the 2'
      OCbz-3'-NMeCbz derivative of azithromycin in vacuum and in DMF. We have shown
      that the methylation of the hydroxy group on C-6 is energetically unfavorable
      compared to the other hydroxy groups in vacuum; the softness values further
      showed that the C-6 anion is not reactive towards CH3I in the methylation
      mechanism. To understand the effect of the solvent on the methylation process,
      detailed molecular dynamics simulations were performed in DMF using the anions at
      the C-4", C-6, C-11 and C-12 positions. We find the conformations of the anions
      not to be affected by the presence of the solvent. The radial distribution
      functions of the solvent molecules around the O- of the anions demonstrate that
      DMF molecules cluster around the C-6 anion. The relative strength of the anion
      solvent interactions reveal that the solvent molecules provide the largest
      stabilization to the C-6 anion and prevent the methylation at this position. The
      latter descriptor was found to be an important factor in explaining the
      experimentally observed selectivity towards the methylation of the C-4", C-6, C
      11 and C-12 anions.

PMID- 15143800
TI  - Molecular dynamics study of peptide segments of the BH3 domain of the
      proapoptotic proteins Bak, Bax, Bid and Hrk bound to the Bcl-xL and Bcl-2
      proteins.
AB  - Overexpression of Bcl-2 and Bcl-xL proteins, both inhibitors of apoptosis or
      programmed cell death, is related to the generation and development of several
      types of cancer as well as to an elevated resistance to chemotherapeutic
      treatments. Given that synthetic peptide fragments of the BH3 domain are capable
      to bind to both proteins and induce apoptosis in cell-free systems and HeLa
      cells, small molecule non-peptide mimics of these peptides can be considered as a
      new therapeutic strategy for the treatment of diseases associated to a deficient
      apoptosis or resistant to the treatments with chemotherapeutic drugs. This
      strategy is supported by experimental evidences about the death of transformed
      cells and sensibilization of tumoral cells by the inhibition of the antiapoptotic
      proteins Bcl-2 and Bcl-xL. In the current work, these proteins complexed with
      X(16BH3), where X designates the proapoptotic proteins Bak, Bax, Bid and Hrk,
      have been modeled in order to establish a pharmacophoric hypothesis that must be
      present in any ligand capable of binding with the antiapoptotic proteins Bcl-2
      and Bcl-xL. The pharmacophore is also used to explain the structural features of
      a set of new small molecule inhibitors of these antiapoptotic proteins.

PMID- 15143806
TI  - Digital moire fringe-scanning method for centering a circular fringe image.
AB  - A digital moire fringe-scanning method for centering a circular fringe image is
      proposed. The image of a nondiffracting beam, whose cross section is a circular
      fringe, is first downloaded onto a computer. The image is then superposed with a
      digital circular grating, whose center is close to the center of the image, to
      generate circular moire fringes. Changing the phase of a digital grating can
      cause moire fringe scanning. The global center of the image can be calculated by
      use of sets of the scanned picture. Because all the image data are used for the
      calculation, the effect of random noise on centering is greatly reduced and the
      center position resolution can reach the order of a subelement of a CCD. The
      measurement of spatial straightness is discussed.

PMID- 15143804
TI  - Broadband, static wave-front generation: Na-Ag ion-exchange phase screens and
      telescope emulation.
AB  - We test the statistical properties of static, atmospherelike wave fronts in glass
      that allow repeatable testing of astronomical adaptive optics instrumentation.
      The technology is mask-structured ion exchange (MSI) in glass and has significant
      advantages over other transmissive technologies. The screens are easy to clean,
      are insensitive to ambient temperature changes, and have high optical-to-near
      infrared transmission. However, the effective coherence length (r0) on each of
      the fabricated screens is systematically too large or, equivalently, the
      fabricated aberrations are too weak. Despite this strong caveat, the screens
      appear to be quite useful: Long-exposure point-spread functions have realistic
      shapes, and power spectrum indices closely match those of the computer-generated
      wave fronts. Most significant, stacking screens with similar r0 values reduced r0
      by the amount predicted by turbulence theory. The refractivity of MSI screens
      remains unmeasured. Finally, we present our design of an optical system that
      emulates the key characteristics of the Very Large Telescope, made to contain
      glass phase screens and to mimic an array of stars for multiconjugate adaptive
      optics system testing.

PMID- 15143807
TI  - Simple three-dimensional laser angle sensor for three-dimensional small-angle
      measurement.
AB  - A simple three-dimensional (3D) laser angle sensor for 3D measurement of small
      angles based on the diffraction theorem and on ray optics analysis is presented.
      The possibility of using position-sensitive detectors and a reflective
      diffraction grating to develop a 3D angle sensor was investigated and a prototype
      3D laser angle sensor was designed and built. The system is composed of a laser
      diode, two position-sensitive detectors, and a reflective diffraction grating.
      The diffraction grating, mounted upon the rotational center of a 3D rotational
      stage, divides an incident laser beam into several diffracted rays, and two
      position-sensitive detectors are set up for detecting the positions of +/-1st
      order diffracted rays. According to the optical path relationship between the
      three angular motions and the output coordinates of the two position-sensitive
      detectors, the 3D angles can be obtained through kinematic analysis. The
      experimental results show the feasibility of the proposed 3D laser angular
      sensor. Use of this system as an instrument for high-resolution measurement of
      small-angle rotation is proposed.

PMID- 15143802
TI  - Force-field parametrization and molecular dynamics simulations of Congo red.
AB  - Congo red, a diazo dye widely used in medical diagnosis, is known to form
      supramolecular systems in solution. Such a supramolecular system may interact
      with various proteins. In order to examine the nature of such complexes empirical
      force field parameters for the Congo red molecule were developed. The
      parametrization of bonding terms closely followed the methodology used in the
      development of the charmm22 force field, except for the calculation of charges.
      Point charges were calculated from a fit to a quantum mechanically derived
      electrostatic potential using the CHELP-BOW method. Obtained parameters were
      tested in a series of molecular dynamics simulations of both a single molecule
      and a micelle composed of Congo red molecules. It is shown that newly developed
      parameters define a stable minimum on the hypersurface of the potential energy
      and crystal and ab initio geometries and rotational barriers are well reproduced.
      Furthermore, rotations around C-N bonds are similar to torsional vibrations
      observed in crystals of diphenyl-diazene, which confirms that the flexibility of
      the molecule is correct. Comparison of results obtained from micelles molecular
      dynamics simulations with experimental data shows that the thermal dependence of
      micelle creation is well reproduced.

PMID- 15143795
TI  - Catalytic oxidation of organic compounds in incineration flue gas by a commercial
      palladium catalyst.
AB  - The object of this study is to investigate the effect of different operation
      conditions on the catalytic oxidation of trace organic compounds [i.e., benzene,
      toluene, ethylbenzene, and xylene (BTEX); and polyaromatic hydrocarbons (PAHs)]
      in incineration flue gas. A commercial Pd-based honeycomb catalyst, which is
      applied to treat flue gas with low organic concentrations and high gas velocity,
      is employed in this study. The investigated parameters include (1) effect of
      different space velocities, (2) effect of heavy metals, (3) effect of acid gas,
      and (4) effect of water vapor and ash particles. In this work, an effective
      catalyst oxidation system is constructed and expected to purify the incineration
      flue gas. Catalyst oxidation is a potential purification system that will meet
      the stricter regulations on the emissions of incineration systems. Experimental
      results showed that the destruction efficiency of PAHs and BTEX in Pd catalyst
      was generally greater than 80%. Decreasing the space velocity increased the
      decomposition efficiency of organic compounds. When the feedstock contained the
      heavy metals Pb and Cr, the oxidation of organic compounds was not inhibited. But
      the presence of Cd significantly decreased the oxidation efficiency. The acid
      gases SO2 and HCl in the flue gas could have influenced the crystal structure of
      PdO and subsequently deactivated/poisoned the Pd catalyst. The effect of water
      vapor on the catalytic destruction of PAHs and BTEX was not obvious.

PMID- 15143805
TI  - Mueller polarimetric imaging system with liquid crystals.
AB  - We present a new polarimetric imaging system based on liquid-crystal modulators,
      a spectrally filtered white-light source, and a CCD camera. The whole Mueller
      matrix image of the sample is measured in approximately 5 s in the transmission
      mode. The instrument design, together with an original and easy-to-operate
      calibration procedure, provides high accuracy over a wide spectral range (500-700
      nm). This accuracy has been assessed by measurement of a linear polarizer at
      different orientations and a thick wedged quartz plate as an example of a
      partially depolarized retarder. Polarimetric images of a stained hepatic biopsy
      with significant fibrosis have been taken at several wavelengths. The optical
      properties of Picrosirius Red stained collagen (diattenuation, retardance, and
      polarizance) have been measured independently from each other between 500 and 700
      nm.

PMID- 15143808
TI  - Effects of fiber-optic probe design and probe-to-target distance on diffuse
      reflectance measurements of turbid media: an experimental and computational study
      at 337 nm.
AB  - Fiber-optic probes are widely used in optical spectroscopy of biological tissues
      and other turbid media. Only limited information exists, however, on the ways in
      which the illumination-collection geometry and the overall probe design influence
      the interrogation of media. We have investigated both experimentally and
      computationally the effect of probe-to-target distance (PTD) on the diffuse
      reflectance collected from an isotropically (Lambertian) scattering target and an
      agar-based tissue phantom. Studies were conducted with three probes characterized
      by either common (single-fiber) or separate (two bifurcated multifiber probes)
      illumination and collection channels. This study demonstrates that PTD, probe
      design, and tissue scattering anisotropy influence the extent of the transport of
      light into the medium, the light-collection efficiency, and the sampling volume
      of collected light. The findings can be applied toward optimization of fiber
      optic probe designs for quantitative optical spectroscopy of turbid media
      including biological tissues.

PMID- 15143803
TI  - Mapping protein pockets through their potential small-molecule binding volumes:
      QSCD applied to biological protein structures.
AB  - Previously we demonstrated a method, Quantized Surface Complementarity Diversity
      (QSCD), of defining molecular diversity by measuring shape and functional
      complementarity of molecules to a basis set of theoretical target surfaces
      [Wintner E.A. and Moallemi C.C., J. Med. Chem., 43 (2000) 1993]. In this paper we
      demonstrate a method of mapping actual protein pockets to the same basis set of
      theoretical target surfaces, thereby allowing categorization of protein pockets
      by their properties of shape and functionality. The key step in the mapping is a
      'dissection' algorithm that breaks any protein pocket into a set of potential
      small molecule binding volumes. It is these binding volumes that are mapped to
      the basis set of theoretical target surfaces, thus measuring a protein pocket not
      as a single surface but as a collection of molecular recognition environments.

PMID- 15143801
TI  - Identifying the binding mode of a molecular scaffold.
AB  - We describe a method for docking of a scaffold-based series and present its
      advantages over docking of individual ligands, for determining the binding mode
      of a molecular scaffold in a binding site. The method has been applied to eight
      different scaffolds of protein kinase inhibitors (PKI). A single analog of each
      of these eight scaffolds was previously crystallized with different protein
      kinases. We have used FlexX to dock a set of molecules that share the same
      scaffold, rather than docking a single molecule. The main mode of binding is
      determined by the mode of binding of the largest cluster among the docked
      molecules that share a scaffold. Clustering is based on our 'nearest single
      neighbor' method [J. Chem. Inf. Comput. Sci., 43 (2003) 208-217]. Additional
      criteria are applied in those cases in which more than one significant binding
      mode is found. Using the proposed method, most of the crystallographic binding
      modes of these scaffolds were reconstructed. Alternative modes, that have not
      been detected yet by experiments, could also be identified. The method was
      applied to predict the binding mode of an additional molecular scaffold that was
      not yet reported and the predicted binding mode has been found to be very similar
      to experimental results for a closely related scaffold. We suggest that this
      approach be used as a virtual screening tool for scaffold-based design processes.

PMID- 15143809
TI  - Determination of collagen fiber orientation in human tissue by use of
      polarization measurement of molecular second-harmonic-generation light.
AB  - Based on the reflection-type polarization measurement of second-harmonic
      generation (SHG) light induced by collagen molecules, we are able to determine
      the collagen fiber orientation in human tissues taken from a cadaver. The
      resulting SHG radar graph shows the direction of the absolute orientation and the
      degree of organization of collagen fibers. To evaluate the probing sensitivity to
      the collagen orientation, we compared the proposed method with other polarimetric
      methods. Use of the proposed method revealed characteristic orientation
      differences among collagen fibers and demonstrated significant inhomogeneity with
      respect to the distribution of collagen orientation in human dentin. The proposed
      method provides a powerful research and diagnostic tool for examining the
      collagen orientation in human tissues.

PMID- 15143812
TI  - Surface characterization from doubly scattered light.
AB  - When a translucent diffuser is illuminated by a speckle pattern, a new speckle
      pattern is produced. We show that the decorrelation of this intensity pattern by
      displacement of the diffusing surface is related to the standard deviation of the
      slope's distribution when the illuminating speckle grain is chosen appropriately
      small. The experimental results are compared with those obtained by measuring the
      angular distribution of the mean scattered intensity, and they show good
      agreement with each other.

PMID- 15143810
TI  - Microsurface plasmon resonance biosensing based on gold-nanoparticle film.
AB  - We use a gold-nanoparticle coated film to achieve highly spatially resolved
      biosensing that is based on localized surface-plasmon resonance. Unlike the
      planar gold film employed for conventional surface-plasmon resonance sensing, the
      gold-nanoparticle film relies exclusively on shifting of the peak extinction
      wavelength for detection of biointeraction and does not depend critically on the
      angle of incidence. These characteristics permit integration of surface-plasmon
      resonance with large-numerical-aperture optics to achieve biosensing with high
      sensitivity and spatial resolution as high as 25 microm.

PMID- 15143813
TI  - Lau array illuminator.
AB  - Spatial coherence can be created by appropriate spatial arrangements of
      incoherent point sources. Lau used a source of extended light and two amplitude
      gratings of identical periods, separated by the quarter Talbot distance, to
      provide coherent light. Because of the two successive amplitude gratings, most of
      the power is lost. By modifying the geometry of the second grating, I designed an
      array illuminator, providing several compression ratios and various topologies of
      the output plane, with significantly reduced losses. To further improve the power
      efficiency of the system, I used a longitudinal mirror system to collect the
      light rays that are lost in the initial Lau setup. Both one- and two-dimensional
      geometries are considered.

PMID- 15143811
TI  - Ultrahigh-resolution full-field optical coherence tomography.
AB  - We have developed a white-light interference microscope for ultrahigh-resolution
      full-field optical coherence tomography of biological media. The experimental
      setup is based on a Linnik-type interferometer illuminated by a tungsten halogen
      lamp. En face tomographic images are calculated by a combination of
      interferometric images recorded by a high-speed CCD camera. Spatial resolution of
      1.8 microm x 0.9 microm (transverse x axial) is achieved owing to the extremely
      short coherence length of the source, the compensation of dispersion mismatch in
      the interferometer arms, and the use of relatively high-numerical-aperture
      microscope objectives. A shot-noise-limited detection sensitivity of 90 dB is
      obtained in an acquisition time per image of 4 s. Subcellular-level images of
      plant, animal, and human tissues are presented.

PMID- 15143817
TI  - Secure holographic memory by double-random polarization encryption.
AB  - A novel optical encryption based on polarization is proposed and applied to a
      holographic memory system. Original binary data are described as two orthogonal
      linear polarization states. These input polarization states can be modulated by
      use of two polarization-modulation masks located at the input and the Fourier
      planes. Each modulation mask can convert an input polarization state into a
      random polarization state. Once encrypted, the polarization state is recorded as
      a hologram. For the decryption, the hologram can generate a vector phase
      conjugate beam. When the same polarization-modulation masks are used, the vector
      phase-conjugate readout can cancel the polarization modulation at each mask, and
      the original polarization state can be recovered. The encryption of the proposed
      method is evaluated numerically. We also present experimental results by
      demonstrating holographic recording in a bacteriorhodopsin film.

PMID- 15143814
TI  - One-dimensional photonic crystals with an amplitude-modulated dielectric constant
      in the unit cell.
AB  - Photonic band structures of one-dimensional photonic crystals with an amplitude
      modulated dielectric constant in the unit cell were studied. With this structure
      two bandgaps in the visible and one in the IR region were predicted. Experimental
      measurements of the two photonic bandgaps in the visible spectrum were made in a
      photonic crystal recorded in a holographic emulsion. Good agreement between
      experimental and theoretical results was obtained.

PMID- 15143815
TI  - Investigation of the diffusion processes in a self-processing acrylamide-based
      photopolymer system.
AB  - Results from the investigation of the diffusion processes in a dry acrylamide
      based photopolymer system are presented. The investigation is carried out in the
      context of experimental research on optimization of the high-spatial-frequency
      response of the photopolymer. Tracing the transmission holographic grating
      dynamics at short times of exposure is utilized to measure diffusion
      coefficients. The results reveal that two different diffusion processes
      contribute with opposite sign to the refractive-index modulation responsible for
      the diffraction grating buildup. Monomer diffusion from dark to bright fringe
      areas increases the refractive-index modulation. It is characterized with
      diffusion constant D0 = 1.6 x 10(-7) cm2/s. A second diffusion process takes
      place during the recording. It decreases the refractive-index modulation and we
      ascribe it to diffusion of short-chain polymer molecules or radicals from bright
      to dark fringe areas. The estimated diffusion coefficient for this process is D0
      = 6.35 x 10(-10) cm2/s. The presence of the second process could be responsible
      for the poor high-spatial-frequency response of the investigated photopolymer
      system. Comparison with the diffusion in photopolymer systems known for their
      good response at high spatial frequencies shows that both investigated diffusion
      processes occur in a much faster time scale.

PMID- 15143818
TI  - Reflective acousto-optic modulation with surface acoustic waves.
AB  - A reflective optical modulator based on acousto-optic modulation of light by a
      mirror corrugated with surface acoustic waves is presented. Modulation of optical
      amplitude, frequency, and phase is demonstrated at visible (633- and 488-nm) and
      deep UV (244-nm) wavelengths. The reflective modulator has eight channels and
      achieves a maximum first-order diffraction efficiency of 6.0%.

PMID- 15143816
TI  - Gamma correction for digital fringe projection profilometry.
AB  - Digital fringe projection profilometry utilizes a digital video projector as a
      structured light source and thus gains great flexibility. However, the gamma
      nonlinearity of the video projector inevitably decreases the accuracy and
      resolution of the measurement. We propose a gamma-correction technique based on
      statistical analysis of the fringe images. The technique allows one to estimate
      the value of gamma from the normalized cumulative histogram of the fringe images.
      By iterating the two steps, gamma estimation and phase evaluation, the actual
      gamma value can be calculated. At the same time the phase distribution of the
      fringe pattern can be solved with higher accuracy. In so doing, neither
      photometric calibration nor knowledge of the device is required. Both computer
      simulation and experiment are carried out to demonstrate the validity of this
      technique.

PMID- 15143820
TI  - Combined temperature lidar for measurements in the troposphere, stratosphere, and
      mesosphere.
AB  - We describe the performance of a combined Raman lidar. The temperature is
      measured with the rotational Raman technique and with the integration technique
      simultaneously. Additionally measured parameters are particle extinction and
      backscatter coefficients and water vapor mixing ratio. In a previous stage of the
      system, instrumental problems restricted the performance. We describe how we
      rebuilt the instrument and overcame these restrictions. As a result, the
      measurement time for the same spatial resolution and accuracy of the rotational
      Raman temperature measurements is reduced by a factor of approximately 4.3, and
      their range could be extended for the first time to the upper stratosphere.

PMID- 15143819
TI  - Effective Mie scattering of a spherical fractal aggregate and its application in
      turbid media.
AB  - An effective Mie-scattering model is developed to deal with the scattering
      property of a spherical fractal aggregate consisting of scattering particles. In
      this model the scattered field of a scattering particle is given by the classical
      Mie-scattering theory. On the basis of the Monte Carlo simulation method, we
      determine the physical parameters of a scattering aggregate, the scattering
      efficiency Q, and the anisotropy value g, as well as their dependence on the size
      and the effective mean-free-path length of a scattering aggregate. Accordingly,
      photon migration through a microscope objective focused into a turbid medium
      including scattering aggregates is simulated to understand the effect of complex
      tissue on image quality.

PMID- 15143823
TI  - Calibration method for multiangle lidar measurements.
AB  - A new method based on a two-angle approach is developed to determine the lidar
      solution constant from scanning elastic lidar data, hence providing a relative
      calibration for each lidar scan. Once the solution constant is determined, the
      vertical profiles of atmospheric extinction can be calculated. With this
      calibration method a minimization technique is used that replaces the linear
      regression used in a known two-angle approach that requires only local
      atmospheric homogeneity over a restricted altitude calibration range rather than
      overall horizontal homogeneity. Lidar signals from at least one pair of elevation
      angles are used, averaged in time when the system is operated in a permanent two
      angle mode, or an arbitrary number of signal pairs is used, when a two
      dimensional lidar scan is being processed. The method is tested extensively with
      synthetic data. The calibration method is a robust tool for determining the
      solution constant to the lidar equation and for obtaining vertical profiles of
      atmospheric extinction.

PMID- 15143822
TI  - Passively Q-switched ceramic Nd3+:YAG/Cr4+:YAG lasers.
AB  - Passively Q-switched ceramic Nd3+:YAG lasers with ceramic Cr4+:YAG saturable
      absorbers are demonstrated. When the lasers are pumped by a 1-W cw laser diode,
      optical-optical efficiency as great as 22% is obtained with Cr4+:YAG of initial
      transmission ranging from 94% to 79%. The results are similar to those in their
      crystalline counterparts. The operation of Brewster's angle and the polarization
      state of the laser output are also investigated.

PMID- 15143821
TI  - Diode-end-pumped electro-optically Q-switched Nd:YLF slab laser.
AB  - We report a very compact Nd:YLF slab laser that is end pumped by a quasi
      continuous-wave diode stack. A hybrid resonator is used to generate high output
      power in a near-diffraction-limited beam (i.e., a beam propogation M2 factor of
      less than 1.2). A pulse energy of 14.3 mJ was obtained with a pulse width of 8.5
      ns at a repetition rate of 500 Hz, which corresponds to a Q-switched peak power
      of 1.68 MW.

PMID- 15143824
TI  - GLITTER: new lidar technique for cloud-base altimetry. Description and initial
      aircraft measurements.
AB  - Knowledge of cloud-base heights is important for climate studies, weather, and
      military operations. Conventional lidar methods monitor cloud depths by direct
      transmission of the beam through the cloud and sensing the backscattered returns.
      These techniques are limited by severe optical scattering by cloud particles to
      thickness <0.5 km. We have conceived of a novel lidar method measurement for
      thick-cloud-base altimetry from above that is not restricted by cloud scattering.
      The new method, known as GLITTER (an acronym for glimpses of the lidar images
      through the empty regions), relies on cloud porosity and diffuse reflection from
      land features to sense cloud bottoms. An aircraft GLITTER lidar measured cloud
      bases at 3.7- and 4.5-km altitudes. These initial results represent a proof-of
      principle demonstration of the new lidar method.

PMID- 15143825
TI  - SAFIRE-A (spectroscopy of the atmosphere by far-infrared emission-airborne):
      optimized instrument configuration and new assessment of improved performance.
AB  - An upgraded configuration of the SAFIRE-A Fourier transform far-infrared
      spectrometer was recently set up, and significant improvements in instrument
      performance were attained during several testing and scientific flights onboard
      the high-altitude research aircraft M55-Geophysica. New features were implemented
      in specific instrument subsystems, such as the pointing system, the reference
      laser interferometer, and the onboard calibration unit, to increase the overall
      instrument functionality and to obtain reliable operation from both the high
      frequency (approximately 120 cm(-1)) and the low-frequency (approximately 23 cm(
      1)) detection channels. Other changes, such as those made in the onboard
      recording system or in the postflight data-transfer procedure, were aimed at
      expanding the capability of unattended operation and at providing a user-friendly
      interface for data downloading and ground servicing. A detailed description of
      these modifications is given, along with a quantitative assessment of the SAFIRE
      A instrument performance.

PMID- 15143826
TI  - Deposition and characterization of silica-based films by helicon-activated
      reactive evaporation applied to optical waveguide fabrication.
AB  - Planar silicon dioxide optical waveguides were deposited by use of a plasma
      activated reactive evaporation system, at a low deposition temperature and with
      reduced hydrogen contamination, on thermally oxidized silicon wafers. The
      deposited films show a refractive-index inhomogeneity of less than 0.1%, a
      thickness nonuniformity of less than 5%, and a material birefringence of
      approximately 5 x 10(-4). Rib-type channel waveguides were formed on the
      deposited films by means of hydrofluoric acid etching. The transmission loss of
      the rib waveguides is determined to be as low as 0.3 dB/cm at a wavelength of
      1310 nm for TE polarization, after subtraction of the calculated leakage and
      scattering losses. Owing to the presence of the OH vibrational overtone band, an
      additional loss peak of 1 dB/cm is found near the 1385-nm wavelength. The
      experimental results of transmission loss at wavelengths of 1310 and 1550 nm are
      compared with analytic expressions for interface scattering and leakage loss.

PMID- 15143827
TI  - Selagoline, a new alkaloid from Huperzia selago.
AB  - A new natural product, named selagoline, and two known alkaloids, huperzine A and
      serratidine, were isolated from Huperzia selago (Lycopodiaceae) collected in
      Iceland. Their structures were determined using 600 and 800MHz one- and two
      dimensional NMR methods supported by Fourier-transform mass spectrometry.
      Possible role of selagoline as a precursor of 5,15-oxidolycopodane, a component
      of the classical alkaloids L28 and L31, is discussed.

PMID- 15143828
TI  - The structure of a new crystalline cevane alkaloid: its identity with
      persicanidine B and harepermine.
AB  - The structure of a new crystalline base (melting point (mp) 167-169 degrees C)
      obtained from Fritillaria imperialis was elucidated as (20R, 25R)-5alpha,17beta
      cevanine-3beta,6beta-diol, X-ray diffraction analysis of the mono-hydrate. The
      base was found to be identical with persicanidine B and also with harepermine.

PMID- 15143830
TI  - Aroma chemical emitted from Gerris paludum insularis.
AB  - An aroma chemical emitted from Gerris paludum insularis was analyzed by means of
      GC and GC-MS. The main constituent was identified as iso amyl alcohol (3-methyl-1
      butanol). The chemical showed a characteristic aroma of Gerris paludum insularis.

PMID- 15143831
TI  - Ultrasound-assisted conversion of toxic beta-asarone into nontoxic bioactive
      phenylpropanoid: isoacoramone, a metabolite of Piper marginatum and Acorus
      tararinowii.
AB  - Ultrasound-assisted synthesis of bioactive isoacoramone (1), a metabolite of
      Piper marginatum and Acorus tararinowii, has been achieved by oxidation of toxic
      beta-asarone (2) with potassium permanganate/copper sulphate/alumina into
      asaronaldehyde (3) followed by treatment with ethylmagnesium iodide to provide 1
      (2,4,5-trimethoxy)phenyl-1-propanol (4) which upon further oxidation with
      potassium permanganate/copper sulphate afforded 1 in 64% yield (overall 32%).
      Toxicological evaluation of 1 reveals it to be nontoxic up to 60 mg/kg b.w.

PMID- 15143829
TI  - Flavonoids of Crataegus microphylla.
AB  - Crataegus microphylla C. Koch is one of the 17 species of Crataegus growing in
      Turkey [H.P.T. Ammon and R. Kaul (1994). Dtsch. Apoth. Ztg., 134, 2433, 2521,
      2631.]. This report is part of a series on the chemical investigations of
      Crataegus species from Turkey. Nine flavonoids have been isolated from the leaves
      and flowers of C. microphylla C. Koch. The amounts of the flavonoids from the
      leaves and flowers of the plant were determined.

PMID- 15143833
TI  - Antioxidants from rape (Brassica campestris vir. Japonica Hara) oil cake.
AB  - A simple but novel compound, S-1-methoxy-1-(3,5-dimethoxy-4-hydroxyphenyl)ethane,
      was isolated as a moderately antioxidative compound from rape (Brassica
      campestris L. subsp. napus) oil cake together with 5 known compounds. Three of
      these compounds, indolacetonitrile, 4-hydroxyindolacetonitrile, and 4
      hydroxyphenylacetonitrile, showed strong antioxidative activity evaluated by the
      ferric thiocyanate method.

PMID- 15143832
TI  - Cytotoxic alkaloids from the marine sponge Thorectandra sp.
AB  - Three beta-carboline alkaloids, Compound 1, 1-deoxysecofascaplysin A (2), and
      fascaplysin (3), were isolated from the aqueous and organic extracts of the
      marine sponge Thorectandra sp. The structures of 1 and 2 were determined on the
      basis of spectral data. Compound 1 inhibited the growth of MCF-7 (breast) with an
      IC50 of 5.9 microg/mL while Compound 2 inhibited the growth of MCF-7 as well as
      OVCAR-3 (ovarian) human tumor cell lines with IC50s of 1.5 and 2.2 microg/mL,
      respectively.

PMID- 15143834
TI  - Glycosidic monoterpenes from Linaria capraria.
AB  - During our systematic study on the species of genus Linaria (Scrophulariaceae)
      present in Italy, we examined the glycosidic fraction of Linaria capraria Moris
      et De Not., a species endemic of Tuscany archipelago. This fraction is
      particularly complex and we considered in this article only the medium polarity
      components. In accordance with previous studies, L. capraria shows acyl
      derivatives of antirrhinoside 1 as specific chemotaxonomic iridoidic markers. L.
      capraria exhibits a complex composition, with regard to iridoidic constituents,
      with several chromatographic problems to be resolved. We then isolated, besides
      the known antirrhinoside 1, two acyl derivatives of antirrhinoside, the 6'-O
      senecioyl derivative, 2, and the 6'-O-angeloyl derivative, 3. In addition a
      glucoside of an acyclic monoterpene, 4, was also isolated, which may be
      correlated to the other monoterpenic glycosides isolated from other species of
      Scrophulariaceae.

PMID- 15143835
TI  - Isolation and synthesis of isodihydropiperlonguminine.
AB  - The hexane extract of dried fruits of Piper longum on fractionation afforded a
      new alkamide, isodihydropiperlonguminine and two phenyl propanoic acid
      derivatives. The structures of these compounds are established based on
      spectroscopic evidence and synthesis.

PMID- 15143837
TI  - Alkaloids from Isopyrum thalictroides L.
AB  - Two new aporphine-benzylisoquinoline alkaloids thaliphine and isothaliphine with
      a new type of ether bridge were isolated from the roots and rhyzomes of Isopyrum
      thalictroides L. (Ranunculaceae). Their structures were established by physical
      and spectral analysis. The known alkaloid N-methylglaucine was isolated for the
      first time from a plant of the family Ranunculaceae.

PMID- 15143836
TI  - Prenylindoles from Tanzanian Monodora and Isolona species.
AB  - 6-(3-Methyl-but-2-enyl)-1,3-dihydro-indol-2-one, annonidine F [3-[6-(3-methyl-but
      2-enyl)-1H-indolyl]-6-(3-methyl-but-2-enyl)-1H-indole], 1H-indole-5-carbaldehyde,
      6-(3-methyl-2-butenyl)-1H-indole, 6-(3-methyl-buta-1,3-dienyl)-1H-indole, 6-(4
      oxo-but-2-enyl)-1H-indole and 3-geranylindole were isolated from Monodora
      angolensis (Annonaceae) while 3-(1,1-dimethyl-but-2-enyl)-5-(3-methyl-but-2-enyl)
      1H-indole (caulidine A), 4-[3-(1,1-dimethyl-but-2-enyl)-1H-indol-5-yl]-but-3-en-2
      one (caulidine B), 5-(3-methyl-2-butenyl)-1H-indole and 5-(3-methylbuta-1,3
      dienyl)-1H-indole were obtained from Isolona cauliflora (Annonaceae); structural
      determination by spectroscopic analysis. Some of the prenylindoles had antifungal
      and antimalarial activities.

PMID- 15143838
TI  - A new dehydroaporphine alkaloid from Papaver fugax.
AB  - A new dehydroaporphine alkaloid (-)-6a,7-dehydrofloripavidine has been isolated
      from the aerial parts of Papaver fugax Poir. (Papaveraceae) collected from
      Erzurum (Eastern Anatolia). (-)-Floripavidine (aporphine) and (-)-mecambrine
      (proaporphine) were isolated as major alkaloids. Other bases present were (+)
      salutaridine (promorphinane) and argentinine (phenanthrene). The presence of
      argentinine has been shown for the first time in the Papaveraceae.

PMID- 15143839
TI  - A new biflavonoid from leaves of Garcinia nervosa.
AB  - The isolation of a new biflavonoid, identified as I-3, II-3, I-5, II-5, I-7, II
      7, I-4', II-4'-octahydroxy [I-2', II-2'] biflavone, from the leaves of Garcinia
      nervosa is reported. The structure was established by chemical and physical means
      (IR, UV, 1H-NMR, 13C-NMR data).

PMID- 15143841
TI  - Retraction of a published article.

PMID- 15143840
TI  - Biologically active metabolites from fungi, 19: new isocoumarins and highly
      substituted benzoic acids from the endophytic fungus, Scytalidium sp.
AB  - Six known metabolites, two new isocoumarins 4 and 8, and one new highly
      substituted benzoic acid derivative 9 were isolated from the ethyl acetate
      culture extract of a fungal endophyte, Scytalidium sp. In addition, another new
      benzoic acid 10 with an unusual 1,2-dicarbonyl side chain was indirectly
      identified from its methylated derivatives 10a-10d.

PMID- 15143842
TI  - The state of psychiatry in Hong Kong: a bird's eye view.

PMID- 15143843
TI  - The Dependent Personality Questionnaire (DPQ): a screening instrument for
      dependent personality.
AB  - BACKGROUND: There are no specific instruments for rating dependent personality,
      although this may be an important subject in clinical practice, where knowledge
      of dependent personality features may influence treatment. AIMS: To develop a
      simple self-rating questionnaire for dependent personality features and compare
      the findings in two groups, one with and one without established dependent
      personality disorder. METHOD: An 8-item Dependent Personality Questionnaire (DPQ)
      was developed and its acceptability and validity tested by administration to 30
      psychiatric patients, half of whom had dependent personality disorder using
      clinical and research data, and the other 15 (pair-matched for age and sex)
      having other psychiatric diagnoses (including other personality disorders) but no
      dependent personality features. RESULTS: The mean score on the dependent
      personality questionnaire (DPQ) was 13.7 in those with dependent personality
      disorder and 7.5 in those without such a disorder (p < .005). The DPQ was also a
      good predictor of the diagnosis of dependent personality disorder, with
      sensitivity, specificity, predicted positive, and predicted negative accuracies
      of 87%. CONCLUSIONS: The results suggest that the DPQ may be a suitable screening
      instrument for dependent personality characteristics.

PMID- 15143847
TI  - Stress, burnout, coping and stress management in psychiatrists: findings from a
      systematic review.
AB  - BACKGROUND: Research into stress among psychiatrists has attempted to identify
      stressors, which can lead to physical illness and psychological distress. AIMS:
      The aim of the study was systematically to review the current evidence for the
      effectiveness of stress management interventions for those working in the
      psychiatric profession. METHOD: A systematic review of the current literature was
      conducted into stress and stress management within the profession of psychiatry.
      RESULTS: Twenty-three international studies were included in the psychiatry
      section of the review. Psychiatrists report a range of stressors in their work,
      including stress associated with their work and personal stresses. One personal
      stress, which psychiatrists find very difficult to cope with is patient suicide.
      Coping strategies include support from colleagues and outside interests. No
      studies evaluated the use of stress-management interventions for psychiatrists.
      CONCLUSIONS: Psychiatry is a stressful profession. Psychiatrists identified
      several stressors in their professional and personal lives.

PMID- 15143846
TI  - Social and health determinants of well being and life satisfaction in Jamaica.
AB  - BACKGROUND: Psychological well being and the degree of satisfaction with life are
      likely to affect a range of social behaviours and determine uptake of health and
      social services. It is important to identify the factors that inform these
      constructs. AIMS: We sought to identify the variables which best predicted
      psychological well being in the Caribbean country, Jamaica and also those
      associated with feelings of satisfaction with life. METHODS: Interviews were
      conducted on young adults aged 15-50 years as part of a sexual decision-making
      survey in Jamaica. Information was collected on a range of social, health and
      demographic variables and a measure of psychological well being--Centre for
      Epidemiological Studies of Depression (CES-D). Satisfaction with life was
      measured using a Likert scale in response to the question 'Are you satisfied with
      your life as a whole?' Multiple regression analyses were used to determine the
      predictors of psychological well being and satisfaction with life. RESULTS: There
      were 2580 respondents (1601 women and 979 men). The mean age was 29.7 years
      (standard deviation 9.2 years). Women had lower levels of psychological well
      being and satisfaction with life. Independent predictors of lower psychological
      well being were having an acute illness, having a chronic illness in women and
      high religious behaviour in men. Satisfaction with life was predicted by younger
      age, marital status and employment. CONCLUSIONS: Our findings suggest that health
      variables are more important for psychological well being while social
      circumstances are more significant for satisfaction with life. There are
      important gender differences in the mediation of psychological well being as well
      as age differences in the variables associated with satisfaction with life.

PMID- 15143845
TI  - Taoism and its impact on mental health of the Chinese communities.
AB  - Spirituality and religious coping is an important and rapidly expanding field in
      recent years. For the Chinese, traditional Taoism may still have a strong impact
      on the mental health of Chinese people. Taoistic concepts of mental health stress
      the transcendence from self and secularity, the dynamic revertism of nature,
      integration with nature and the pursuit of the infinite. Compared with western
      concepts of mental health, Taoism advocates self-transcendence, integration with
      the Law of Nature, inaction and infinite frame of reference instead of social
      attainment, self-development, progressive endeavor and personal interpretation.
      By means of a case illustration, the writer tries to describe its impacts on help
      seeking, stress and coping, and the meaning of life of a Chinese family. Its
      generalization to different types of Chinese communities is also discussed.

PMID- 15143844
TI  - Race and psychiatric services in post-apartheid South Africa: a preliminary study
      of psychiatrists' perceptions.
AB  - OBJECTIVES: The primary objective of this study was to examine the perception of
      the quality of psychiatric services five years after apartheid, and specifically
      whether care for black patients had improved. DESIGN: A survey was distributed to
      South African psychiatrists during a national congress and by mail. The
      questionnaire focused on the quality of psychiatric care in general, for black
      and white patients, the racial composition of each respondent's psychiatric
      practice currently, and the racial composition of the psychiatric practice during
      apartheid. RESULTS: Psychiatric services in South Africa were viewed as
      deteriorating. The end of apartheid has done little to improve the quality of
      psychiatric care for both black and white patients. Although less pronounced,
      racial inequality in psychiatric care continues to exist. Psychiatric practices
      continue to be overrepresented with white patients. CONCLUSION: There remains a
      differential in quality of psychiatric care and further monitoring should
      continue. Continued efforts to improve racial equality and the need for greater
      awareness of cultural issues need to be addressed. Limitations of this study
      included possible social desirability bias, use of subjective rather than
      objective measures, and a survey that was limited in scope.

PMID- 15143849
TI  - The value of treatment-goal themes for treatment planning and outcome evaluation
      of psychiatric inpatients.
AB  - BACKGROUND: The taxonomy of treatment-goal themes of the Bern Inventory of
      Treatment Goals (BIT-T) has shown to be a comprehensive coding system for
      outpatient use. AIM: The current study examines the value of the BIT-T for
      treatment planning and outcome evaluation of psychiatric inpatients. METHOD: The
      1991 treatment goals of 675 predominantly non-psychotic psychiatric inpatients
      were coded using the BIT-T. Ratings of goal-related changes by patients and
      length of stay were used as outcome criteria. RESULTS: The BIT-T showed to be
      reliable and exhaustive. Distributions of goal themes are partially associated
      with diagnoses. Goal-related improvements as well as length of hospital stay
      differed depending on the themes of patients' treatment goals. CONCLUSIONS:
      Coding of treatment-goal themes with the BIT-T provides researchers as well as
      practitioners with valuable information that goes beyond psychopathological
      diagnoses. This information can be used clinically for treatment planning as well
      as outcome evaluation.

PMID- 15143851
TI  - Indoor mold exposure associated with neurobehavioral and pulmonary impairment: a
      preliminary report.
AB  - Recently, patients who have been exposed indoors to mixed molds, spores, and
      mycotoxins have reported asthma, airway irritation and bleeding, dizziness, and
      impaired memory and concentration, all of which suggest the presence of pulmonary
      and neurobehavioral problems. The author evaluated whether such patients had
      measurable pulmonary and neurobehavioral impairments by comparing consecutive
      cases in a series vs. a referent group. Sixty-five consecutive outpatients
      exposed to mold in their respective homes in Arizona, California, and Texas were
      compared with 202 community subjects who had no known mold or chemical exposures.
      Balance, choice reaction time, color discrimination, blink reflex, visual fields,
      grip, hearing, problem-solving, verbal recall, perceptual motor speed, and memory
      were measured. Medical histories, mood states, and symptom frequencies were
      recorded with checklists, and spirometry was used to measure various pulmonary
      volumes and flows. Neurobehavioral comparisons were made after individual
      measurements were adjusted for age, educational attainment, and sex. Significant
      differences between groups were assessed by analysis of variance; a p value of
      less than 0.05 was used for all statistical tests. The mold-exposed group
      exhibited decreased function for balance, reaction time, blink-reflex latency,
      color discrimination, visual fields, and grip, compared with referents. The
      exposed group's scores were reduced for the following tests: digit-symbol
      substitution, peg placement, trail making, verbal recall, and picture completion.
      Twenty-one of 26 functions tested were abnormal. Airway obstructions were found,
      and vital capacities were reduced. Mood state scores and symptom frequencies were
      elevated. The author concluded that indoor mold exposures were associated with
      neurobehavioral and pulmonary impairments that likely resulted from the presence
      of mycotoxins, such as trichothecenes.

PMID- 15143848
TI  - The development of the therapeutic community in correctional establishments: a
      comparative retrospective account of the 'democratic' Maxwell Jones TC and the
      hierarchical concept-based TC in prison.
AB  - BACKGROUND: The correction-based therapeutic community (TC) is one of the most
      described treatment modalities for (substance abusing) incarcerated offenders.
      The origins and development of the therapeutic community have been traced back to
      two independent traditions: the American hierarchical concept-based TC and the
      British democratic Maxwell Jones-type TC. Both branches have developed
      independently, targeting different people and tackling diverse problems. AIMS: To
      demonstrate that there are clear and undeniable similarities between the 'two'
      prison-based therapeutic communities. METHOD: A comparative historical review of
      the literature and a critical discussion and comparison. RESULTS: The links
      between the democratic and hierarchical therapeutic communities are summarised
      under five headings: social learning and behavioural modification; permissiveness
      and modelling; democracy and hierarchy; communalism and community as method;
      reality testing and 'acting as if'. CONCLUSIONS: The 'two' correction-based
      therapeutic communities are on converging pathways. Far from being oppositional
      models, they can be regarded as being complementary.

PMID- 15143852
TI  - Effects of toxic exposure to molds and mycotoxins in building-related illnesses.
AB  - The authors studied 100 patients who had been exposed to toxic molds in their
      homes. The predominant molds identified were Alternaria, Cladosporium,
      Aspergillus, Penicillium, Stachybotrys, Curvularia, Basidiomycetes, Myxomycetes,
      smuts, Epicoccus, Fusarium, Bipolaris, and Rhizopus. A variety of tests were
      performed on all, or on subgroups of, these patients. Sensitivities and exposures
      were confirmed in all patients by intradermal skin testing for individual molds
      (44-98% positive), and by measurement of serum antibodies. Abnormalities in T and
      B cells, and subsets, were found in more than 80% of the patients. The findings
      of trichothecene toxin and breakdown products in the urine, serum antibodies to
      molds, and positive intradermal skin tests confirmed mycotoxin exposure.
      Respiratory signs (e.g., rhinorrhea, sinus tenderness, wheezing) were found in
      64% of all patients, and physical signs and symptoms of neurological dysfunction
      (e.g., inability to stand on the toes or to walk a straight line with eyes
      closed, as well as short-term memory loss) were identified in 70% of all
      patients. Objective abnormal autonomic nervous system tests were positive in all
      100 patients tested. Brain scans, conducted using triple-head single photon
      emission computed tomography, were abnormal in 26 (86%) of 30 (subgroup of the
      100) patients tested. Objective neuropsychological evaluations of 46 of the
      patients who exhibited symptoms of neurological impairment showed typical
      abnormalities in short-term memory, executive function/judgment, concentration,
      and hand/eye coordination.

PMID- 15143853
TI  - Use of functional brain imaging in the evaluation of exposure to mycotoxins and
      toxins encountered in Desert Storm/Desert Shield.
AB  - In this retrospective analysis the authors compared brain scintigrams, performed
      using triple-head single-photon emission computed tomography (tripleSPECT), of
      subjects who were judged clinically impaired from exposure to toxins during the
      Desert Storm/Desert Shield military action, and of subjects exposed to
      mycotoxins, with those of normal controls. The scintigrams for both exposed
      groups exhibited similar patterns of abnormalities, which were consistent with
      neurotoxic impairment. The authors conclude that further study is needed to
      determine whether mycotoxin exposure may be a cause of abnormalities seen in
      tripleSPECT images.

PMID- 15143854
TI  - Mixed mold mycotoxicosis: immunological changes in humans following exposure in
      water-damaged buildings.
AB  - The study described was part of a larger multicenter investigation of patients
      with multiple health complaints attributable to confirmed exposure to mixed-molds
      infestation in water-damaged buildings. The authors present data on symptoms;
      clinical chemistries; abnormalities in pulmonary function; alterations in T, B,
      and natural killer (NK) cells; the presence of autoantibodies (i.e., antinuclear
      autoantibodies [ANA], autoantibodies against smooth muscle [ASM], and
      autoantibodies against central nervous system [CNS] and peripheral nervous system
      [PNS] myelins). A total of 209 adults, 42.7 +/- 16 yr of age (mean +/- standard
      deviation), were examined and tested with (a) self-administered weighted health
      history and symptom questionnaires; (b) standardized physical examinations; (c)
      complete blood counts and blood and urine chemistries; (d) urine and fecal
      cultures; (e) thyroid function tests (T4, free T3); (f) pulmonary function tests
      (forced vital capacity [FVC], forced expiratory volume in 1 sec [FEV1.0], and
      forced expiratory flow at 25%, 50%, 75%, and 25-75% of FVC [FEF25, FEF50, FEF75,
      and FEF2(25-75)]); (g) peripheral lymphocyte phenotypes (T, B, and NK cells) and
      mitogenesis determinations; and (h) a 13-item autoimmune panel. The molds-exposed
      patients reported a greater frequency and intensity of symptoms, particularly
      neurological and inflammatory symptoms, when compared with controls. The
      percentages of exposed individuals with increased lymphocyte phenotypes were: B
      cells (CD20+), 75.6%; CD5+CD25+, 68.9%; CD3+CD26+, 91.2%; CD8+HLR-DR+, 62%; and
      CD8+CD38+, 56.6%; whereas other phenotypes were decreased: CD8+CD11b+, 15.6% and
      CD3-CD16+CD56+, 38.5%. Mitogenesis to phytohemagglutinin was decreased in 26.2%
      of the exposed patients, but only 5.9% had decreased response to concanavalin A.
      Abnormally high levels of ANA, ASM, and CNS myelin (immunoglobulins [Ig]G, IgM,
      IgA) and PNS myelin (IgG, IgM, IgA) were found; odds ratios for each were
      significant at 95% confidence intervals, showing an increased risk for
      autoimmunity. The authors conclude that exposure to mixed molds and their
      associated mycotoxins in water-damaged buildings leads to multiple health
      problems involving the CNS and the immune system, in addition to pulmonary
      effects and allergies. Mold exposure also initiates inflammatory processes. The
      authors propose the term "mixed mold mycotoxicosis" for the multisystem illness
      observed in these patients.

PMID- 15143856
TI  - Chronic sinusitis: defective T-cells responding to superantigens, treated by
      reduction of fungi in the nose and air.
AB  - In this study, the author used endoscopic sinus photography to study the effects
      of reduction of fungi in the nose, and in environmental air, on the sinus mucosa
      of 639 patients diagnosed with chronic rhinosinusitis. Sinus mucosal photographs
      were taken before and after reduction of fungal load in the nose and air, to
      determine if there was an optimum environmental air fungal load associated with
      sinus mucosal recovery to normal appearance. Systemic symptoms associated with
      fungal exposure, which resolved when fungus was removed from the patient and the
      environmental air and reappeared with recurrent environmental fungal exposure,
      are also discussed and are termed systemic fungal symptoms. Interventions
      consisted of nasal fungal load reduction with normal saline nasal irrigations and
      antimicrobial nasal sprays, and environmental air fungal load reduction with high
      efficiency particulate air (HEPA) filtration in combination with ionizers or
      evaporation of a solution of botanical extract. Main outcome measures were
      obtained with environmental air 1-hr gravity-plate fungal colony counts, laser
      air particle counts, and endoscopic sinus photography. Blood levels of
      immunoglobulins IgG and IgE for 7 common molds were also determined. After
      intervention, 94% of patients who used antimicrobial nasal sprays and who reduced
      their environmental fungal air count to 0-4 colonies per 1-hr agar gravity-plate
      exposure (n = 365) exhibited normal sinus mucosa by endoscopic exam.
      Environmental air fungal counts that exceeded 4 colonies resulted in sinus
      mucosal abnormalities ranging from edema, to pus and/or nasal polyps at higher
      counts. Neutralization of allergy, and/or surgery, were used as appropriate
      following implementation of environmental measures. On the basis of these
      observations, as well as detailed clinical experience and a review of the current
      literature, the author hypothesizes that the pathogenesis of chronic
      rhinosinusitis, allergic fungal sinusitis, and systemic fungal symptoms is a
      genetic defect at the variable beta chain helper T-cell receptor (TCR Vbeta) site
      which requires the presence of an antigen (fungus). Chronic sinusitis patients
      who have recurring exposure to environmental air that contains fungal
      concentrations in excess of 4 colonies per 1-hr agar plate exposure appear to
      have an increased risk of persistent chronic sinusitis and/or systemic symptoms,
      regardless of the medical treatment provided.

PMID- 15143857
TI  - Health symptoms caused by molds in a courthouse.
AB  - A majority of occupants of a newly renovated historic courthouse in Calgary,
      Alberta, Canada, reported multiple (3 or more) health-related symptoms, and
      several reported more than 10 persistent symptoms. Most required at least 1 day
      outside of the building to recover from their symptoms. Molds that produce
      mycotoxins, such as Stachybotrys chartarum and Emericella nidulans, were
      identified in the building, along with fungal organisms of the genera
      Aspergillus, Penicillium, Streptomyces, Cladosporium, Chaetomium, Rhizopus/Mucor,
      Alternaria, Ulocladium, and Basidiomycetes. Renovations to this historic had
      building failed to provide adequate thermal and vapor barriers, thus allowing
      moist indoor air to migrate into the building enclosure, causing condensation to
      develop. Mold grew on the condensation and was dispersed throughout the
      courthouse, including on furniture and files. The courthouse was closed and a new
      facility was modified with low-offgassing materials, better ventilation and air
      filtration, and strict building maintenance to accommodate those occupants of the
      older building who had developed multiple chemical sensitivities.

PMID- 15143855
TI  - Antibodies to molds and satratoxin in individuals exposed in water-damaged
      buildings.
AB  - Immunoglobulin (Ig)A, IgM, and IgG antibodies against Penicillium notatum,
      Aspergillus niger, Stachybotrys chartarum, and satratoxin H were determined in
      the blood of 500 healthy blood donor controls, 500 random patients, and 500
      patients with known exposure to molds. The patients were referred to the
      immunological testing laboratory for health reasons other than mold exposure, or
      for measurement of mold antibody levels. Levels of IgA, IgM, and IgG antibodies
      against molds were significantly greater in the patients (p < 0.001 for all
      measurements) than in the controls. However, in mold-exposed patients, levels of
      these antibodies against satratoxin differed significantly for IgG only (p <
      0.001), but not for IgM or IgA. These differences in the levels of mold
      antibodies among the 3 groups were confirmed by calculation of z score and by
      Scheffe's significant difference tests. A general linear model was applied in the
      majority of cases, and 3 different subsets were formed, meaning that the healthy
      control groups were different from the random patients and from the mold-exposed
      patients. These findings indicated that mold exposure was more common in patients
      who were referred for immunological evaluation than it was in healthy blood
      donors. The detection of antibodies to molds and satratoxin H likely resulted
      from antigenic stimulation of the immune system and the reaction of serum with
      specially prepared mold antigens. These antigens, which had high protein content,
      were developed in this laboratory and used in the enzyme-linked immunosorbent
      assay (ELISA) procedure. The authors concluded that the antibodies studied are
      specific to mold antigens and mycotoxins, and therefore could be useful in
      epidemiological and other studies of humans exposed to molds and mycotoxins.

PMID- 15143859
TI  - [Type 1 diabetes mellitus and eating disorders. An over- or underestimated
      comorbidity?].

PMID- 15143861
TI  - Prevalence and clinical manifestations of eating disorders in Austrian
      adolescents with type-1 diabetes.
AB  - OBJECTIVES: To investigate prevalence and clinical manifestations of DSM-IV
      clinical eating disorders and subsyndromal eating problems among adolescents with
      type-1 diabetes. METHOD: A clinical sample of 251 adolescents with type-1
      diabetes was recruited from multiple centres. Of these adolescents, 199 (96 girls
      and 103 boys--79.3% participation rate) with a mean age of 14.1 years (SD: 2.6)
      were screened for eating disorders and then underwent DSM-IV-based clinical
      assessment of eating disorders by interview. RESULTS: 11.5% of the girls and none
      of the boys with type-1 diabetes had DSM-IV eating disorders, whereas 13.5% of
      the girls and 1% of the boys had subsyndromal problems of eating and shape. Girls
      with both type-1 diabetes and a clinical or subclinical eating disorder had a
      significantly higher body-mass index than those without eating problems.
      CONCLUSION: This Austrian study supports cumulative international evidence that
      among youths with type-1 diabetes, adolescent girls and especially those having a
      higher body mass are particularly vulnerable for manifesting pathology of eating,
      weight and shape. Thus, this particular population requires screening of eating
      behaviour and relevant psychopathology, close monitoring, and psychosocial
      interventions through cooperative efforts of specialised centres.

PMID- 15143867
TI  - Gas gangrene due to Clostridium perfringens in two injecting drug users in
      Vienna, Austria.
AB  - We describe two cases of severe myonecrotic infections caused by Clostridium
      perfringens in injecting drug users (IDUs) in Vienna, Austria. Clostridial
      myonecrosis, or gas gangrene, is a clostridial infection primarily of muscle
      tissue. C. perfringens is isolated in 90% of these infections. Other clostridial
      species isolated are C. novyi, C. septicum, C. histolyticum, C. fallax, and C.
      bifermentans. Classically, clostridial myonecrosis has an acute presentation and
      a fulminant clinical course. It is diagnosed mainly on a clinical basis. The
      infection may be so rapidly progressive that any delay in recognition or
      treatment may be fatal. The onset is sudden, often within 4 to 6 hours after an
      injury. An early clinical finding is sudden severe pain in the area of infection.
      Swelling and edema in the area of infection is pronounced. At surgery, the
      infected muscle is dark-red to black, is noncontractile, and does not bleed when
      cut. Crepitus, although not prominent, is sometimes detected. We were able to
      demonstrate spores that were morphologically indistinguishable from spores of C.
      perfringens in a drug sample obtained from case 2. General practitioners and
      accident and emergency staff should be aware of the possibility of C. perfringens
      infection in IDUs, especially if injection into soft tissue is suspected.

PMID- 15143858
TI  - [Future perspectives in the treatment of type 2 diabetes].

PMID- 15143871
TI  - Follow-up and mortality profiles in the Miyagi Cohort Study.
AB  - BACKGROUND: Findings from a large-scale population-based prospective cohort would
      lead us to better understanding of the relationship between lifestyle and health,
      thus better provision of strategies for disease prevention and health promotion.
      METHODS: We conducted a baseline survey with two self-administered questionnaires
      regarding lifestyle and personality on the residents aged 40 to 64 years in 14
      municipalities of Miyagi Prefecture, Japan, during June through August, 1990. Out
      of the eligible 51,925 residents, 47,605 (91.7%) responded to the lifestyle
      questionnaire and formed the cohort under study. We then have been following up
      the subjects for mortality, migration, and incidence of cancer. RESULTS: During
      the follow-up from June 1990 through March 2001, 2,536 subjects (5.3%) died and
      2,166 subjects (4.5%) emigrated. The distribution of the causes of death among
      the study subjects was quite consistent with the national average. CONCLUSIONS:
      In this cohort study, both the participation rate and the follow-up rate are
      satisfactorily high. We expect this Miyagi Cohort Study to provide the society
      with evidence for health promotion and disease prevention.

PMID- 15143870
TI  - Lifestyle and mortality in the Miyagi Cohort Study.

PMID- 15143862
TI  - Normal regulation of elevated plasma ghrelin concentrations in dialysis patients.
AB  - BACKGROUND: Chronic renal failure is often associated with malnutrition, and
      malnourished patients are subject to increased morbidity and mortality. Therefore
      plasma concentrations of the stomach-derived peptide hormone ghrelin, which has
      been shown to exert potent GH-releasing and appetite-stimulating effects, were
      determined and correlated with nutritional parameters. METHODS: Twenty-four
      patients (15 male, 9 female) undergoing hemodialysis (HD) were studied. In
      addition, six patients were studied before and one hour after ingestion of a meal
      and five were studied immediately before and at the end of the dialysis session.
      RESULTS: Chronic renal insufficiency was associated with significantly elevated
      ghrelin levels (320.1 +/- 57 fmol/mL vs. 75.6 +/- 12.4 fmol/mL in controls; p <
      0.007). Plasma ghrelin concentrations were also significantly higher in the 16
      normal-weight patients than in the eight overweight or obese patients (399.6 +/-
      76.3 fmol/mL vs. 161.1 +/- 41.3 fmol/mL; p < 0.03). Ingestion of food induced a
      decrease in five out of six patients tested (mean 242.3 +/- 66.5 fmol/mL vs. 186
      +/- 30.7 fmol/mL; n.s.). HD also resulted in a significant decrease of elevated
      ghrelin concentrations: ghrelin was in the normal range at the end of HD in four
      of the five patients tested. Plasma ghrelin concentrations did not correlate with
      nutritional parameters except for cholinesterase which was negatively correlated
      to ghrelin. CONCLUSION: Plasma ghrelin concentrations are elevated in HD. The
      fact that ghrelin concentrations are higher in normal-weight than in overweight
      or obese HD patients and suppressed after ingestion of a meal suggests that the
      regulation of ghrelin release is retained in HD patients, albeit shifted to a
      higher level.

PMID- 15143869
TI  - [Reliability of home monitoring with event recording compared with
      polysomnography in infants].

PMID- 15143872
TI  - Cancer incidence profiles in the Miyagi Cohort Study.
AB  - BACKGROUND: There were few prospective cohort studies in Japan using cancer
      incidence as an endpoint. METHODS: We conducted a baseline survey with two self
      administered questionnaires regarding lifestyle and personality on the residents
      aged 40 to 64 years in 14 municipalities of Miyagi Prefecture, Japan, during June
      through August, 1990. Out of the eligible 51,921 residents, 47,605 (91.7%)
      responded to the lifestyle questionnaire and formed the cohort under study. We
      collated the list of subjects in the cohort with the Miyagi Prefectural Cancer
      Registry data through December 31, 1997. To identify the same person between two
      data, we used four personal characteristics (sex, name, birthday, and
      municipality of dwelling). RESULTS: We ascertained 1,718 cases of incident
      cancer. In men, gastric cancer was the leading site of cancer (27.7%), followed
      by lung cancer and colon cancer. In women, breast cancer was the most common
      (19.6%), followed by gastric cancer and colon cancer. CONCLUSIONS: By record
      linkage with regional cancer registry data, it becomes possible for us to
      investigate the effect of various life-styles on cancer incidence in the Miyagi
      Cohort Study. We expect this data to contribute to the progress of research on
      cancer etiology and cancer prevention.

PMID- 15143866
TI  - [Spinal cord injuries in infants and juveniles].
AB  - Trauma of the infant or juvenile spine is a very rare occurrence (less than 2%).
      Nevertheless, it is almost always dramatic. In 21 years 1630 patients with spinal
      cord injuries were treated. Of these, 21.7% (357 patients) had injuries in the
      area of the cervical spine. 23 patients (1.4%) were younger than 17.5 years, 8 of
      them were younger than 10 years. In 10 cases the cause was a traffic accident, in
      7 cases it was a jump in too shallow water. In 4 times other leisure activities
      were the cause. A fall from a window sill and a falling tree were further
      reasons. Neck segment C0 to C3 was involved eight times, segment C3 to C7/Th1 was
      involved 15 times. The average age of the group with injuries in C0 to C3 was 5.6
      years, in the group with injuries of segments C3 to C7/Th1 it was 15.8 years. In
      11 cases the trauma caused complete tetraplegia, in six cases the paralysis was
      partial. In six further cases no neurological deficit occurred. 14 cases were
      treated surgically, six were treated conservatively. Four children younger than
      10 years with complete tetraplegia died. In seven cases tetraplegia persisted;
      out of six patients with incomplete neurological deficit three improved and three
      patients recovered completely.

PMID- 15143865
TI  - [Long-term results of percutaneous transmyocardial laser revascularization
      therapy at the University of Vienna Medical Center].
AB  - INTRODUCTION: Percutaneous transmyocardial laser revascularization (PTMR) was
      used for treating patients with therapy refractory angina pectoris who are not
      amenable for angioplasty or bypass surgery ("no-option patients"). The aim of
      this study was to evaluate the short- and long-term results of PTMR-interventions
      performed at the University of Vienna between February 1999 and May 2000.
      PATIENTS AND METHODS: Twenty-four "no-option" patients underwent PTMR. The
      chronically ischemic myocardial areas were determined by perfusion scintigraphy;
      after coronary angiography and contrast ventriculography 10 patients were treated
      with the Biosense laser using 3D-NOGA-mapping guidance and 14 patients with the
      Eclipse laser using biplane fluoroscopic guidance. After an average follow-up
      period (FUP) of 7.7 +/- 4.2 months, all patients underwent perfusion
      scintigraphy, coronary angiography and contrast ventriculography. Global and
      regional left ventricular (LV) function were calculated by the area-length
      method. RESULTS: The ischemic myocardial areas of the patients were treated with
      an average of 16 laser points. In one patient, an intramural hematoma caused by
      the Biosense laser catheter was observed, in another patient the ventricular wall
      was perforated by the Eclipse laser (both events were resolved conservatively);
      during the in-hospital stay 2 patients suffered from severe angina pectoris and
      in one patient a pacemaker was implanted. During the 7-month-FUP one patient had
      a myocardial infarction; in one patient a stent implantation, in another one
      coronary bypass surgery had to be performed (in not-lasered areas), 2 patients
      died. Thus, the composite MACE rate was 33.3%. Angina class improved
      significantly during the FUP, but a trend to deterioration of global ejection
      fraction was observed. The rest and late rest myocardial perfusion remained
      unchanged. CONCLUSION: While the angina class of the patients improved
      significantly, no significant change of myocardial perfusion but a trend to
      deterioration of LV function after the FUP were observed.

PMID- 15143868
TI  - [Austrian Society for Pulmonary Diseases and Tuberculosis. Consensus concerning
      the management of chronic obstructive pulmonary diseases (COPD). Revised draft
      2004].

PMID- 15143873
TI  - Cigarette smoking and mortality in Japan: the Miyagi Cohort Study.
AB  - BACKGROUND: We examined the association between smoking and all-cause mortality
      among Japanese men and women. METHODS: In 1990, 18,945 men and 17,107 women in
      Miyagi Prefecture in rural northern Japan (40-64 year of age) completed a self
      administered questionnaire including items on smoking. Cox regression was used to
      estimate relative risk (RR) of mortality according to smoking categories, with
      adjustment for age, education, marital status, past history of diseases,
      drinking, body mass index, walking, and dietary variables. During 11 years of
      follow-up, 1,209 men and 499 women had died. RESULTS: Multivariate RRs of all
      cause mortality for current smokers as compared with never smokers were 1.71 (95%
      confidence interval, 1.44-2.03) for men and 1.44 (95% confidence interval, 1.06
      1.94) for women. Among men, risk in past smokers who had quit smoking for 15
      years or longer was not different from the risk in never smokers (RR, 0.97; 95%
      confidence interval, 0.68-1.39). Of all deaths, 34% in men and 4% in women were
      attributable to current or past smoking. CONCLUSIONS: This study indicates that
      smoking increases the risk of premature death among middle-aged Japanese men and
      women and that substantial proportion of death, especially for men, is
      attributable to smoking.

PMID- 15143864
TI  - Renal functional reserve in patients with Type 1 diabetes mellitus.
AB  - AIM: Decreased renal functional reserve might precede incipient diabetic
      nephropathy in patients with Type 1 diabetes. The aim of this study was to assess
      the relationship between renal functional reserve and easily assessable estimates
      of systemic endothelial dysfunction in normoalbuminuric patients with Type 1
      diabetes and diabetic retinopathy. METHODS: Renal functional reserve was
      calculated as the relative change in glomerular filtration rate after protein
      ingestion. Glomerular filtration rate was measured using pharmacokinetic
      compartmental analysis of single-shot plasma sinistrin clearance. We measured the
      activity of von Willebrand factor and concentrations of C-reactive protein and
      apolipoprotein B, as easily assessable estimates of systemic endothelial
      dysfunction. RESULTS: Twenty-two patients were studied. Renal functional reserve
      was inversely associated with activity of von Willebrand factor (R=-0.431,
      p=0.045) and, in a multivariate model, with concentration of C-reactive protein
      (R=0.652, p=0.031). CONCLUSION: Renal functional reserve is inversely associated
      with concentration of C-reactive protein in normoalbuminuric patients with Type 1
      diabetes and diabetic retinopathy. This finding provides evidence that decreased
      renal functional reserve might reflect endothelial dysfunction. We speculate that
      decreased renal functional reserve might possibly show as an early marker of
      diabetic nephropathy.

PMID- 15143874
TI  - Alcohol consumption and mortality in Japan: the Miyagi Cohort Study.
AB  - BACKGROUND: We examined the association between alcohol consumption and all-cause
      mortality in Japanese men and women. METHODS: From June through August 1990, a
      total of 39,076 subjects (20,660 men and 18,416 women) in 14 municipalities of
      Miyagi Prefecture in rural northern Japan (40-64 years of age) completed a self
      administered questionnaire that included information about alcohol consumption
      and various health habits. During 11 years of follow-up, we identified 1,879
      deaths (1,335 men and 544 women). We used Cox proportional-hazards regression to
      estimate relative risk (RR) of all-cause mortality according to categories of
      alcohol consumption and to adjust for age, education, marital status, past
      histories of chronic diseases, body mass index, smoking, walking and dietary
      variables. RESULTS: Among men, the risk for all-cause mortality was significantly
      higher in past drinkers than never-drinkers (multivariate RR, 1.86; 95%
      confidence interval [CI], 1.50-2.29). There was a dose-response association
      between alcohol consumption and the risk of all-cause mortality among current
      drinking men: multivariate RRs in reference to never-drinkers (95% CI) were 1.10
      (0.90-1.33), 1.17 (0.96-1.42), 1.16 (0.96-1.40), and 1.62 (1.32-1.99) in current
      drinkers who consumed less than 22.8 g, 22.8-45.5 g, 45.6-68.3 g, and 68.4 g or
      more alcohol per day, respectively (P for trend<0.001). Similar association was
      observed among women (P for trend=0.005). CONCLUSIONS: The results indicated that
      alcohol consumption tended to be associated with linear increase in risk of all
      cause mortality among Japanese men and women, and the association was remarkable
      for younger men.

PMID- 15143863
TI  - Urinary albumin excretion is correlated to fibrinogen levels and protein S
      activity in patients with type 1 diabetes mellitus without overt diabetic
      nephropathy.
AB  - The aim of the study was to test the hypothesis that in diabetic patients without
      overt nephropathy there may be a correlation between the activity of natural
      anticoagulant proteins and glomerular dysfunction. Assays for functional activity
      of proteins S and C, measurements of urinary albumin excretion, lipid parameters
      and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus
      and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria
      had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years;
      p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S
      activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of
      retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with
      normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25,
      p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05),
      total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy
      (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2
      diabetes mellitus and microalbuminuria had significantly higher apoprotein B
      levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with
      normoalbuminuria, and apoprotein B was significantly correlated to albumin
      excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus
      with fibrinogen, protein S and C activity, cholesterol, triglycerides,
      haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters
      (r=0.53; p<0.003), there was significant independent correlation of fibrinogen
      (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy
      (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes,
      relative elevation of fibrinogen level and protein S activity appear in the early
      stages of development of diabetic nephropathy, and may be related to the
      pathogenesis of diabetic kidney disease.

PMID- 15143860
TI  - [Future targets in the treatment of type 2 diabetes].
AB  - Prevention and treatment of type 2 diabetes mellitus (T2DM) and the metabolic
      syndrome represent a major clinical challenge, because effective strategies such
      as fat restriction and exercise are difficult to implement into diabetes
      treatment. Based on the increasing knowledge on the pathogenesis of T2DM, new
      therapeutic approaches are currently under investigation. Potential targets of
      new therapeutic approaches include: (i) Inhibition of hepatic glucose production,
      (ii) stimulation of glucose-dependent insulin secretion, (iii) enhancement of
      insulin signal transduction, and (iv) reduction of body fat mass. Agonists of
      glucagon-like-peptide 1 (GLP-1) and antagonists of dipeptidylpeptidase IV, which
      inactivates GLP-1, stimulate glucose-dependent insulin secretion, improve
      hyperglycemia and are already tested in clinical trials. In humans, glucagon
      antagonists and an amylin analogue reduce glucagon-dependent glucose production.
      The glucose-lowering effect of current modulators of lipid oxidation is not
      pronounced and their use could be limited by side effects. In addition to
      clinically approved thiazolidendiones, new agonists of the peroxisome
      proliferator activator receptor gamma (PPAR gamma) as well as combined PPAR
      alpha/gamma agonists are developed at present. The direct modulation of insulin
      signal transduction is still limited to experimental studies.

PMID- 15143875
TI  - Walking and mortality in Japan: the Miyagi Cohort Study.
AB  - BACKGROUND: Although many studies in western populations demonstrated that time
      spent walking was associated with a reduced risk of all-cause mortality, data on
      Japanese has been sparse. METHODS: In 1990, 20,004 men and 21,159 women in Miyagi
      Prefecture in rural northern Japan (40-64 year of age) completed a self
      administered questionnaire including a question on time spent walking. Cox
      regression was used to estimate relative risk (RR) of mortality according to
      three levels of walking (30 minutes or less, between 30 minutes and one hour, and
      one hour or more), with adjustment for age, education, marital status, past
      history of diseases, smoking, drinking, body mass index, and dietary variables.
      During 11 years of follow-up, 1,879 subjects had died. RESULTS: Time spent
      walking was inversely associated with risk of all-cause mortality: compared with
      men and women who walked one hour or more per day, multivariate RR (95%
      confidence intervals) was 1.06 (0.95-1.19) for subjects who walked between 30
      minutes and one hour per day, and 1.16 (1.04-1.29) for subjects who walked 30
      minutes or less per day (P for trend=0.007). Shorter duration of walking was
      associated with increased mortality among men who were never smokers (P for
      trend=0.081) and past smokers (P for trend=0.026), but not among currently
      smoking men (P for trend=0.751). We observed similar effect modification for
      women. CONCLUSIONS: Time spent walking was associated with a reduced risk for all
      cause mortality, especially among nonsmoking men and women.

PMID- 15143876
TI  - Body mass index and mortality in Japan: the Miyagi Cohort Study.
AB  - BACKGROUND: The relation between body mass index (BMI) and mortality is not well
      established. The objective of this study was to examine the association in
      Japanese adults. METHODS: In 1990, 18,740 men and 20,870 women in Miyagi
      Prefecture in rural northern Japan (40-64 years of age) completed a self
      administered questionnaire including height and weight. Cox regression was used
      to estimate relative risk (RR) of mortality according to levels of BMI, with
      adjustment for age, marital status, smoking, drinking, walking, and weight change
      since 20 years of age. RESULTS: During 11 years of follow-up, 1,121 men and 567
      women had died. Compared with the referent BMI category (23.0-24.9), women in the
      highest BMI category (BMI>30.0) had a RR of death of 1.64 (95% confidence
      interval (CI), 1.09-2.49) and men and women in the lowest BMI categories
      (BM1<18.5) had a RR of death of 2.06 (95% CI, 1.49-2.84) and 1.83 (95% CI, 1.17
      2.88), respectively, after adjustment for potential confounders and after
      exclusion of deaths occurring in the first three years of follow-up. We did not
      observe significant differences in mortality for subjects with wide range of BMI
      (18.5 or higher in men and 18.5 to 29.9 in women). CONCLUSIONS: The risk of death
      from all causes increases in lean men and women, and obese women in this cohort.

PMID- 15143879
TI  - Is obesity a favorable factor for resectability of rectal cancer?
AB  - BACKGROUND/AIMS: It is well established that unresectable rectal tumors have a
      detrimental effect on long-term survival. Predictive factors for resectability
      focused on the body mass index and surgeon case volume were assessed in the
      present study. METHODOLOGY: Data of 387 patients with rectal cancer and 284
      patients with colon tumor who underwent elective surgical exploration during two
      periods (1986-1992 and 1994-2001) were evaluated. Univariate and multivariate
      analysis was performed to estimate the predictive factors for resectability of
      rectal cancer. The ratio of unresectable rectal and colon tumors was compared in
      subgroups of patients selected by body mass index. RESULTS: The observed rate of
      resectability of rectal cancer was 78%. Coexisted distant metastases, low
      caseload of surgeons, body mass index < 25 kg/m2, tumor location < or = 12 cm and
      the first treatment period were associated with low rate of resectability. The
      ratio of unresectable tumors treated by surgeons with low case volume varied
      significantly with body mass index in rectal cancers (< 20 = 52%, 20-24.9 = 29%,
      25-29.9 = 16%, > or = 30 = 19%) but not in colon tumors. CONCLUSIONS: In respect
      to resectability of rectal cancer there was significant difference between
      surgeons with medium and low case volume. Patient's obesity seemed to be a
      favorable factor for resectability of tumors located in the rectum but not in the
      colon when operations were performed by surgeons with low case volume.

PMID- 15143878
TI  - The impact of splenectomy or splenic artery ligation on the outcome of a living
      donor adult liver transplantation using a left lobe graft.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the impact of splenectomy
      or splenic artery ligation on the outcome in living donor adult liver
      transplantation (LDALT) using a left lobe graft. METHODOLOGY: Forty-eight LDALT
      cases using a left lobe graft were enrolled in this study. The patients were
      classified into two groups: Group A (n=40), in which neither a splenectomy nor a
      splenic artery ligation was performed, and Group B (n=8), in which a splenectomy
      (n=6) or a splenic artery ligation (n=2) was performed. Indications for
      splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having
      splenic aneurysms. RESULTS: None of the patients receiving a splenectomy or a
      splenic artery ligation experienced any septic complication in this series. The
      graft-recipient weight ratio in group B tended to be smaller than in group A. In
      group B, all patients were classified into Child's class C or B. The incidence of
      esophageal varices in group B was significantly higher than in group A. Moreover,
      the platelet count and the white blood cell count in group B were significantly
      lower than in group A. No statistical difference was found in postoperative
      functional cholestasis and intractable ascites. None of the participants in group
      B experienced both postoperative hyperbilirubinemia and intractable ascites,
      which were characterized as a small-for-size graft after LDALT. The patient
      survival rate in group B seems to be better than in group A. In a majority of the
      cases the portal pressure as well as the portal vein flow after a splenectomy
      decreased in comparison to that before the splenectomy. CONCLUSIONS: Splenectomy
      or splenic artery ligation is considered to be beneficial for improving the
      outcome in LDALT using a left lobe graft.

PMID- 15143877
TI  - Health practices and mortality in Japan: combined effects of smoking, drinking,
      walking and body mass index in the Miyagi Cohort Study.
AB  - BACKGROUND: Evidence is limited regarding the association between the
      combinations of multiple health practices and mortality. METHODS: In 1990, 28,333
      men and women in Miyagi Prefecture in rural northern Japan (40-64 year of age)
      completed a self-administered questionnaire. A lifestyle score was calculated by
      adding the number of high-risk practices (smoking, consuming > or = 22.8 g
      alcohol/d, walking < 1 hr/d, body mass index < 18.5 or > or = 30.0). Cox
      regression was used to estimate relative risk (RR) of mortality according to the
      lifestyle score, with adjustment for age, education, marital status, past history
      of diseases, and dietary variables. During 11 years of follow-up, 1,200 subjects
      had died. RESULTS: We observed linear increase in risk of death associated with
      increasing number of high-risk practices: compared with men who had no high-risk
      practices, multivariate RRs for men who had 1 to 4 practices were 1.20, 1.66,
      1.94, and 3.96, respectively (P for trend<0.001), and corresponding RRs for women
      were 1.31, 2.14, 3.98, 5.56, respectively (P for trend<0.001). A unit increase in
      the number of high-risk practices corresponded to being 2.8 and 4.8 years older
      for men and women, respectively. CONCLUSIONS: In this prospective cohort study of
      middle-aged men and women in rural Japan, a larger number of high-risk practices
      was associated with linear increase in risk of all-cause mortality.

PMID- 15143880
TI  - The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine in node
      positive pancreatic cancer.
AB  - BACKGROUND/AIMS: The effects of gemcitabine in postoperative adjuvant
      chemotherapy were evaluated in patients suffering from locally advanced
      pancreatic cancer with lymph node metastases. The results were compared with
      those of our historical control patients treated by surgery alone. METHODOLOGY:
      Twenty-one patients with node-positive pancreatic cancer who had undergone a
      pancreatic resection with curative intent over the five years up to February
      2003, were enrolled in this study. Nine cases received postoperative adjuvant
      chemotherapy with biweekly administration of 1000 mg/m2 gemcitabine, while the
      remaining 12 cases underwent surgery without any adjuvant chemotherapy. RESULTS:
      The chemotherapy was well tolerated with only mild symptomatic and hematologic
      toxicities. The overall cumulative survival rates of the chemotherapy and surgery
      alone groups were 86% and 75% at one year, and 50% and 0% at two years, with a
      median survival of 20.3 months and 15.4 months, respectively (p=0.0084). The
      disease-free interval was also significantly greater in the chemotherapy group
      compared with the surgery-alone group (p=0.0244). CONCLUSIONS: Adjuvant systemic
      chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects
      and improved the survival rate of patients with node-positive pancreatic cancer.
      Although further investigation is needed to confirm these results, gemcitabine is
      a promising agent for the treatment of resectable advanced pancreatic cancer.

PMID- 15143881
TI  - Expression of DNA repair protein: MYH, NTH1, and MTH1 in colorectal cancer.
AB  - BACKGROUND/AIMS: Oxidative stress is one of the causative agents of
      carcinogenesis. The DNA repair protein: MYH, NTH1 and MTH1 eliminate the
      oxidative DNA damage. In various tumors, overexpression of MTH1 has been
      reported. This is the first report demonstrating the expression of those proteins
      in colorectal cancer. METHODOLOGY: We investigated the expression of MYH, NTH1
      and MTH1 by immunohistochemical typing methods in colorectal cancers obtained
      from consecutive patients undergoing surgery at the University of Tokyo hospital.
      RESULTS: High MYH immunoreactivity was detected in 57% of cases (46/81), which
      showed a significant correlation with the depth of tumor (p=0.04). Cytoplasmic
      expression of NTH1 was detected in 35% of cases (28/81), which showed a
      significant correlation with lymph node metastasis (p=0.001), histological grade
      according to the Dukes' Classification (p=0.005), and disease-free survival
      (p=0.04). High MTH1 immunoreactivity was detected in 84% of cases (68/81), which
      showed a significant correlation with tumor location (p=0.04). CONCLUSIONS: The
      expression pattern of DNA repair protein for oxidative DNA damage showed a
      significant correlation with aggressive features of colorectal cancer such as the
      depth of tumor, and lymph node metastasis, as well as with Dukes' classification
      and disease-free survival.

PMID- 15143882
TI  - Treatment of colorectal cancer with synchronous bilobar liver metastases with
      simultaneous bowel and liver resection plus radiofrequency ablation.
AB  - Patients with synchronous bilobar colorectal liver metastases usually have an
      extent or distribution of the metastases that precludes curative resection.
      Recently radiofrequency ablation has been proved to safely control liver
      metastases but a combination of radiofrequency ablation with more than liver
      resection is rarely performed. We report two patients with colorectal primary and
      synchronous classically unresectable bilobar liver metastases treated with a
      combination of bowel and liver resection plus radiofrequency ablation. In the
      first patient we performed left colectomy, left hepatic lobectomy and
      radiofrequency ablation of lesions in segments I and VII. In the second patient
      we performed low anterior resection, wedge resections for three superficially
      placed lesions in segments V and VIII, and radiofrequency ablation of five more
      deeply located lesions in segments III, IV, VI and VII. Both patients recovered
      uneventfully. At the eighth month, the first patient developed three new liver
      metastases that were treated with subsequent radiofrequency ablation and at the
      tenth and seventh months of follow-up respectively, both patients are disease
      free. In conclusion, combination of bowel and liver resection plus radiofrequency
      ablation expands the possibilities to treat more patients with colorectal cancer
      having synchronous bilobar unresectable liver metastases.

PMID- 15143886
TI  - Self-expanding metallic stent for benign biliary strictures: seven-year follow
      up.
AB  - We report two cases of benign biliary strictures managed by metallic stent
      placement because the patients refused surgical repair. One patient is a 67-year
      old man who had a stricture of the right hepatic duct and a bile leak following a
      cholecystectomy. The second patient is a 50-year-old man who had a stricture of
      the left hepatic duct following a right hepatic lobectomy for hepatolithiasis.
      For treatment of these bile duct strictures, a Gianturco-Rosch Z stent was placed
      in the former case and a Wallstent in the latter. Luminal patency of the stent
      was maintained for 7 years in the former case but in the latter, luminal stenosis
      of the stent was induced soon after placement. However, in the former, bile
      stasis in the left hepatic duct system, which emptied into the side of the stent,
      gradually developed without signs or symptoms of cholangitis or biliary
      obstruction. Therefore, the use of metallic stents for benign biliary stricture
      remains controversial. However, if metallic stent placement is the only
      therapeutic option, it is necessary to maintain bile flow not only through the
      stent but also in the bile ducts which flow into the side of the stent.

PMID- 15143884
TI  - Endoscopic sphincterotomy in patients with "acalculus" cholangitis associated
      with juxtapapillary diverticula.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate patients who underwent
      endoscopic sphincterotomy for "acalculus" cholangitis associated with
      juxtapapillary diverticula. METHODOLOGY: In a retrospective study we analyzed 87
      patients who underwent endoscopic sphincterotomy for cholangitis; the cholangitis
      considered "acalculus", when outlining the extra- and intrahepatic bile ducts, we
      could not observe any intraluminal defect or stricture, and during the clearing
      of the bile ducts with the balloon, after endoscopic sphincterotomy, there was no
      evidence of stones, fragments of stones or sludge. Patients who had undergone
      previous endoscopic sphincterotomy, or who had additional pancreatobiliary
      diseases were excluded from this study. There were 11 patients with "acalculus"
      cholangitis associated with juxtapapillary diverticula, and sufficient clinical
      data available for this study. RESULTS: Nine patients presented pain, fever, and
      jaundice. In two patients diagnosis was established via the test of abnormal
      liver biochemistry. Seven patients had positive blood cultures and three of them
      developed confusion and hypotension. Endoscopic sphincterotomy succeeded in all
      cases; no evidence of stones, fragments of stones or sludge was recorded during
      the clearing of bile ducts, after endoscopic sphincterotomy, with the balloon.
      Five patients presented mild post-endoscopic sphincterotomy complications
      successfully treated. In the follow-up period, from 4 months to 7 years after
      endoscopic sphincterotomy, none of the patients developed symptoms of
      cholangitis. CONCLUSIONS: We recommend endoscopic sphincterotomy in patients with
      "acalculus" cholangitis associated with juxtapapillary diverticula, despite the
      absence of obvious obstruction, and the possible morbidity which is inherent with
      an invasive procedure like endoscopic sphincterotomy.

PMID- 15143885
TI  - Endoscopic papillary balloon dilation for treatment of common bile duct stones.
AB  - BACKGROUND/AIMS: Use of endoscopic papillary balloon dilation (EPBD) for the
      treatment of common bile duct stones has increased in recent years, owing to its
      simplicity and its advantage of preserving sphincter function. It has been
      reported that EPBD is associated with a lower risk of bleeding, but a higher risk
      of pancreatitis than endoscopic sphincterotomy. However, there have been few
      reports on studies of post-EPBD pancreatitis. This report concerns the use of
      EPBD at our department for the treatment of common bile duct stones and early
      postoperative complications, with a focus on pancreatitis. METHODOLOGY: The study
      was conducted in 63 patients with choledocholithiasis, including 4 patients with
      cirrhosis and 21 patients with periampullary diverticula. The stones were
      extracted after EPBD conducted with an 8-mm dilatation balloon. RESULTS: Complete
      removal of stones was achieved in 53 out of 63 patients (84.1%). Pancreatitis
      meeting the criteria of Cotton et al. occurred in 7 of the 63 patients (11.1%),
      while 12 patients (19.5%) were affected when milder cases of pancreatitis were
      included. Severe pancreatitis occurred in 1 patient only. Cholangitis occurred in
      3 patients (4.8%) and basket impaction occurred in 1 patient (1.6%), but no
      serious complications such as bleeding or perforation were encountered.
      CONCLUSIONS: These results suggest that EPBD is an effective procedure for the
      treatment of common bile duct stones, with a low risk of serious complications.

PMID- 15143883
TI  - Anti-retrovirals and immunosuppressive drug interactions in a HIV-positive
      patient after liver transplantation.
AB  - We report a case of drug-related toxicity after liver transplantation for
      hepatocellular carcinoma in a HIV-HCV co-infected patient. Before transplant the
      patient was on a triple antiretroviral therapy (zidovudine and lamivudine and
      efavirenz) with a stable CD4+ cell count >500 cells/microL. Liver transplantation
      was performed with a liver graft showing a 10% of macrosteatosis and with a graft
      to-recipient body weight ratio of 1.3. Immunosuppression was achieved with
      tacrolimus, azathioprine and steroids. The antiretroviral therapy was resumed in
      the first postoperative day as the early graft function was in the normal range.
      After a few hours the patient showed myoglobinuria, rhabdomyolysis and a fast
      deteriorating graft function. All drugs were withdrawn except steroids and an
      empiric therapy with riboflavin and glutathione was maintained for five days
      until myoglobinuria ended. Nevertheless the serum levels of tacrolimus remained
      in the therapeutic range for six days when it was reintroduced at a reduced
      dosage (0.01 mg/kg/die). The postoperative course was complicated by tense
      ascites and severe hyperbilirubinemia without any rejection episodes. The patient
      was discharged 48 days post-transplantation with a good liver function. During
      the following year no signs of aggressive HCV-HIV recurrences were observed and
      the patient is maintaining a CD4+ cells count >400 without antiretroviral
      therapy.

PMID- 15143887
TI  - Portal vein thrombosis complicated with disseminated intravascular coagulation
      due to acute cholecystitis.
AB  - We herein present the case of a 53-year-old man who suffered from portal vein
      thrombosis complicated with disseminated intravascular coagulation due to acute
      cholecystitis. Although gabexate mesilate and antibiotics were administered and
      endoscopic nasobiliary drainage was performed, only percutaneous transhepatic
      gallbladder drainage performed on the sixth hospital day improved his systemic
      condition and a recanalization of the portal vein was achieved. Regarding the
      strategy for the treatment of patients with disseminated intravascular
      coagulation, both an early diagnosis and prompt treatment for the underlying
      diseases are considered to be extremely important. Since both a hypercoagulate
      state and cholecystitis are considered to be etiological causes of portal vein
      thrombosis, clinicians should be aware that thrombosis may present as a
      complication in such patients.

PMID- 15143888
TI  - Successful surgical treatment for metachronous advanced cancers of the
      gallbladder and the common bile duct--case report.
AB  - A 73-year-old woman with a tentative diagnosis of gallbladder cancer had
      undergone cholecystectomy with liver resection and dissection of regional lymph
      nodes. Pathological examination of the resected specimen revealed well
      differentiated papillary adenocarcinoma of the gallbladder with subserosal
      invasion. No evidence of metastasis was noted in the dissected lymph nodes. After
      surgery, she had been disease free in the follow-up study. Ten years after
      surgery, however, carcinoma arising from the common bile duct was newly found,
      and pancreaticoduodenectomy with regional lymph nodes dissection was performed.
      Histological examination confirmed well-differentiated adenocarcinoma of the
      common bile duct. Lymph nodes had no evidence of malignancy. The patient has been
      doing well with no evidence of recurrence 20 and 10 years after each operation,
      respectively. Apparently, these two cancers occurred independently and each
      surgical treatment for this patient was successful.

PMID- 15143891
TI  - Pancreaticobiliary maljunction in monozygotic twins--a case report.
AB  - We experienced a case of pancreaticobiliary maljunction in monozygotic twins.
      While one of the twins suffered from gallbladder cancer with poor prognosis, the
      other was not associated with biliary malignancy. Ultrasonography, endoscopic
      ultrasonography, and magnetic resonance cholangiopancreatography are effective in
      diagnosis of this disorder before occurrence of biliary cancers. This case is not
      only of academic interest for familial occurrence, but also of clinical interest
      in the early detection of pancreaticobiliary maljunction.

PMID- 15143889
TI  - Surgery for segmental primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is an uncommon chronic hepatobiliary disorder, and
      the definitive surgical treatment for symptomatic primary sclerosing cholangitis
      is liver transplantation. Although some cases with primary sclerosing cholangitis
      treated with hepaticojejunostomy or partial hepatectomy have been reported, the
      indications for these procedures and their long-term results have not been well
      defined or studied. We present three patients with segmental primary sclerosing
      cholangitis, and discuss the indication of surgical treatment for primary
      sclerosing cholangitis excluding liver transplantation. Three patients with
      segmental primary sclerosing cholangitis of the common bile duct and the hepatic
      ducts were treated by hepaticojejunostomy with partial resection of the common
      bile duct. We investigated clinical features such as angiography,
      cholangiography, and surgical treatment outcomes. It was difficult to
      differentiate primary sclerosing cholangitis from a cholangioma preoperatively,
      despite the use of cytology, angiography, and cholangiography. Two of the three
      patients were preoperatively suspected to have cholangioma. Segmental primary
      sclerosing cholangitis was diagnosed operatively. All patients were treated
      hepaticojejunostomy and achieved long-term survival. Although liver
      transplantation is the treatment of choice for primary sclerosing cholangitis, in
      cases of segmental primary sclerosing cholangitis, local resection of the
      involved structures may be curative. Resection of a discrete lesion may provide
      many years of survival with a good quality of life, in some cases obviating the
      need for liver transplantation.

PMID- 15143890
TI  - A recurrent case of an early gallbladder carcinoma after laparoscopic
      cholecystectomy.
AB  - A 71-year-old woman diagnosed with gallstones and chronic cholecystitis was
      admitted to our hospital in October 1997, and laparoscopic cholecystectomy was
      performed. After the operation, early gallbladder carcinoma, which had
      superficially spread to the whole gallbladder restricted to mucosa (pT1a) by
      histology, was identified. Six weeks later, liver bed resection, bile duct
      dissection and regional lymph node dissection were performed. Histological
      examination revealed that cancer cells had been microscopically disseminated to
      the hepatoduodenal ligament and invaded into the lymphatic vessels. The
      postoperative course was uneventful. She died of peritoneal recurrence of her
      gallbladder cancer 14 months after the second operation.

PMID- 15143892
TI  - Regular hemodialysis reverses gastric mucosal atrophy of patients with chronic
      renal failure.
AB  - BACKGROUND/AIMS: Gastric mucosa of patients with chronic renal failure on regular
      hemodialysis is known to retain fundic glands relatively intact, but no evidence
      for regeneration of fundic glands by hemodialysis has been provided to date. This
      study was performed to investigate endoscopically and histopathologically if
      hemodialysis to treat renal failure would regenerate the background gastric
      mucosa and to elucidate factors associated with the mucosal regeneration.
      METHODOLOGY: First, the relationship between duration of hemodialysis and the
      degree of atrophy of the background gastric mucosa was investigated in patients
      with chronic renal failure treated and not treated by hemodialysis. Treated
      patients were further divided into long-term group treated for 4 years or longer
      and short-term group treated for shorter than 4 years. The degree of atrophy of
      gastric mucosa was evaluated by hematoxylin-eosin staining, PAS-alucian blue
      staining and immunohistochemical staining to detect Ki-67 expression using biopsy
      specimens obtained from gastric mucosa. The labeling index is the proportion of
      positively labeled cells with respect to the total number of cells. The
      proliferative index was calculated by multiplying the labeling index and the
      proliferative zone (length of the area between the uppermost and lowest labeled
      cells). Serum gastrin, glucagon and cholecystokinin were assayed as well as urine
      epidermal growth factor to elucidate factors associated with regeneration of
      gastric mucosa. Helicobacter pylori infection was examined by ELISA. RESULTS: In
      the long-term group, the degree of atrophy of gastric mucosa was endoscopically
      evaluated to be C1 type. In both of the two hemodialysis groups, endoscopically
      identified fundic gland region was histologically confirmed to be fundic glands
      by both hematoxylin-eosin staining and PAS-alucian blue staining. Epithelial cell
      proliferative index was significantly higher in long-term and short-term
      hemodialysis group than non-hemodialysis group (P=0.0001). No significant
      difference in serum gastrin, glucagon and cholecystokinin as well as urine
      epidermal growth factor was detectable among the three groups. Most patients of
      both hemodialysis groups were H. pylori-negative. CONCLUSIONS: A possibility of
      regeneration of the background gastric mucosa in proportion to the duration of
      hemodialysis was suggested on the basis of histopathological evidence. The
      observed regeneration of gastric mucosa was ascribable to elimination of factors
      associated with atrophy of gastric mucosa including H. pylori by hemodialysis.

PMID- 15143893
TI  - Von Willebrand gene expression in damaged human liver.
AB  - BACKGROUND/AIMS: von Willebrand factor (vWf) is an adhesive glycoprotein known to
      play a role in hemostasis and in tissue injury. It is found in high levels in
      plasma of patients with acute hepatic failure and chronic liver disease. The aim
      of this study was to investigate the pattern of tissue vWf in acute liver failure
      in humans. METHODOLOGY: We studied vWf immunostaining and mRNA expression in the
      liver of three patients with fulminant liver failure, two patients with chronic
      liver disease, and two controls. PECAM-1 (CD31) immunostaining and mRNA
      expression were used as an additional endothelial marker. RESULTS: In chronic
      liver cirrhosis, vWf deposits were strongly detected at the scar-parenchyma
      interface. In fulminant hepatic failure, intense deposits were seen in tissue
      sections in the area of necrosis. A similar pattern of immunostaining was seen
      with PECAM-1. vWf transcripts were abundant in the liver of patients with chronic
      disease and minimally expressed in patients with acute hepatic failure and in
      controls. CONCLUSIONS: vWf is deposited within the liver sinusoids early after
      liver damage. The factor is only partially produced locally during the acute
      phase of the disease, but is overproduced in chronic disease states. These
      changes may suggest a role for vWf in liver injury and repair.

PMID- 15143894
TI  - Changing trends in the management of Klatskin tumor.
AB  - BACKGROUND/AIMS: To evaluate the long-term outcome of a multidisciplinary
      approach for advanced Klatskin tumor involving the hepatic hilus. METHODOLOGY: A
      retrospective analysis was undertaken in 110 patients between 1993 and 2003. The
      patients were divided into Group A (n=42) and Group B (n=58). Group A patients
      underwent local excision of the tumor and Group B patients underwent combined
      tumor and liver resection with or without resection of the regional vascular
      structures. On admission, all patients underwent percutaneous transhepatic
      biliary drainage. Where hepatectomy was planned, portal vein branch ligation and
      transection was done ipsilateral to the liver lobe where the tumor was present.
      An arterial catheter was introduced into the hepatic artery at the end of the
      surgery, for adjuvant locoregional immunochemotherapy, which was carried out in
      all patients. The second-stage resectional surgery was carried out 35 days later.
      RESULTS: The overall mean survival for Group A patients was 29 months (range 14
      to 76). The mean disease-free survival was 28 months (range 10-52). Five-year
      survival rate was 5% and five-year disease-free survival was 0%. The overall mean
      survival for Group B patients was 39 months (range 28 to 79). The mean disease
      free survival was 32 months (range 17-72). Five-year survival rate was 20% and
      five-year disease-free survival was 10%. CONCLUSIONS: The concept of a
      multidisciplinary approach has significantly improved survival in patients with a
      grave disease like Klatskin tumor.

PMID- 15143897
TI  - Contrast-enhanced, wide-band phase-inversion power Doppler imaging of hepatic
      focal nodular hyperplasia.
AB  - BACKGROUND/AIMS: To determine whether examination of hepatic focal nodular
      hyperplasia by wide-band, phase-inversion sonography offers any advantages over
      power and color Doppler sonography in the depiction of specific characteristics
      of these pathologies. METHODOLOGY: Twenty-six patients were examined. The
      presence of focal nodular hyperplasia was confirmed by ultrasound-guided biopsy,
      surgical resection, dynamic helical computed tomography or magnetic resonance.
      All patients, prior to enhanced sonography, had undergone B-mode gray-scale
      sonography, color Doppler, and power Doppler examinations. After injection of 2.5
      g of Levovist intravenously, analysis of the contrast agent arrival was performed
      by wide-band, phase-inversion power Doppler sonography. RESULTS: The B-mode gray
      scale sonography, color and power Doppler sonography were non-specific for focal
      nodular hyperplasia in 14 cases in our examination. However based on the wide
      band, phase-inversion power Doppler sonography findings all patients with focal
      nodular hyperplasia were diagnosed. All typical anatomic features of focal
      nodular hyperplasia such as "star sign" or "spoke-wheel" pattern were clearly
      visible. In 3 cases, computed tomography and magnetic resonance imaging had
      failed to disclose pathology while phase-inversion sonographic images were
      completely suggestive which was later finally confirmed by histologic
      examination. CONCLUSIONS: Our data demonstrate the usefulness of wide-band, phase
      inversion power Doppler sonography in the differential diagnosis of hepatic focal
      nodular hyperplasia by visualizing all characteristic anatomic details.

PMID- 15143898
TI  - Hepatitis B core antigen in liver tissue from HBs-positive, HBe-negative
      patients.
AB  - BACKGROUND/AIMS: We aimed to study the relationship between HBcAg in liver
      tissue, histological and biochemical activity and serum HBV-DNA levels among
      HBeAg-negative patients. METHODOLOGY: 49 biopsy specimens taken from 16 females
      and 29 males were studied. Immunostaining for HBcAg was performed with
      commercially available kits (Dako). Serum HBV-DNA was detected by the
      hybridization method, in case of negative hybridization, repeated by PCR.
      RESULTS: HBcAg was found in 16 biopsy specimens (32.6%) (group I)--in 10 cases in
      hepatocytes nuclei and cytoplasm, in 5 in the nuclei and in one case in cytoplasm
      only. 15 out of 16 patients were serum HBV-DNA positive. Seven patients showed
      chronic liver disease of moderate or severe activity with HBcAg expression both
      in the nuclei and cytoplasm. Group II consisted of 33 patients who were HBcAg
      negative. In 7 patients HBV-DNA was not found by hybridization or by PCR. In
      eleven patients ALT and AST activity exceeded 1.5x the ULN. ALT and AST differed
      significantly between group II and I. CONCLUSIONS: In our opinion
      immunohistochemical examination is an essential part of classification to
      antiviral treatment. HBcAg immunostaining should be performed in every HBeAg
      negative patient to exclude reasons for aminotransferase elevation other than HBV
      infection.

PMID- 15143901
TI  - Modification of lymph node dissection for colon cancer by clinical diagnosis.
AB  - BACKGROUND/AIMS: Less invasive procedures for colon cancer that are available now
      increase the needs of modified lymph node dissection. The aim of the present
      study is to establish oncologically safe criteria for modifying lymph node
      dissection for colon cancer by clinical diagnosis. METHODOLOGY: We evaluated the
      central extent of lymph node metastasis in 276 patients who underwent curative
      surgery for colon cancer according to clinicopathologic factors and analyzed the
      accuracy of clinical assessment of the factors. RESULTS: Only the degree in depth
      of invasion determined the maximum extent of lymph node metastasis. None of pTis
      pT2 tumors showed metastasis to nodes along the main vessels including apical
      nodes, demonstrating that patients with pTis-pT2, but not pT3-pT4, tumors could
      be candidates for modified lymph node dissection. While the accuracy in clinical
      assessment of depth for pTis, pT1, and pT2 tumors was only 59.1%, 73.7%, and
      53.6%, respectively, none of the clinically assessed as Tis or T1 tumors was
      finally diagnosed as a pT3-pT4 tumor. On the other hand, 30.8% of T2 tumors were
      revealed to be pT3 tumors. CONCLUSIONS: Modification of lymph node dissection by
      clinical diagnosis should be performed for Tis-T1 but not for T2-T4 tumors when
      bowel resection is performed.

PMID- 15143900
TI  - Rectal cancer surgery with sphincter preservation: functional results related to
      the level of anastomosis. Clinical and instrumental study.
AB  - BACKGROUND/AIMS: Unsatisfactory functional results have been reported not only
      after coloanal anastomosis, but also after anterior resection with colorectal
      anastomosis. The aim of this study is to establish functional outcome predictive
      factors related to surgical technique and especially the real impact of residual
      rectum length to identify patients who could benefit from colonic pouch
      reconstruction. METHODOLOGY: Sphincter preservation was achieved in 214 of 327
      patients who underwent surgery for rectal cancer. Patients have been subdivided
      according to the level of anastomosis measured by a rigid proctoscope from the
      anal verge. In 93 patients functional results have been assessed by clinical
      control and anorectal manometry. RESULTS: Functional alterations such as leakage
      (13%), incontinence (5%), urgency (5%) and difficulty in evacuation (10%)
      appeared in patients who underwent anterior resection with anastomosis 4 to 6 cm
      from the anal verge. Nevertheless, comparing anterior resection with anastomosis
      6 to 8 cm and that with anastomosis 4 to 6 cm rectal compliance was the only
      parameter whose difference is statistically significant. CONCLUSIONS: This result
      makes us to believe that patients who undergo anterior resection with no more
      than 2-3 cm of residual rectum could benefit from a colonic pouch reconstruction.

PMID- 15143899
TI  - Lugol staining pattern in background epithelium of patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND/AIMS: Squamous cell carcinoma of the esophagus often arises in the
      setting of chronic esophagitis. We investigated whether chronic esophagitis was
      associated with carcinogenesis in the esophageal squamous epithelium.
      METHODOLOGY: Videoendoscopy with Lugol staining was performed in 70 patients with
      invasive carcinoma of the esophagus. We especially focused the study on
      background epithelium of the esophagus, then background epithelium was classified
      into two groups according to differences in Lugol staining patterns. Following
      Lugol solution spraying, background epithelium showing uniform greenish-brown
      staining was defined as having a uniform pattern. In contrast, when multiple
      Lugol-unstained speckles were present throughout the esophagus, the pattern was
      defined as speckled. Furthermore, we also investigated whether glycogenic
      acanthosis is present or not in background epithelium. RESULTS: Chronic
      esophagitis was present in 11 of 70 patients (16%) with invasive carcinoma,
      indicating a speckled pattern in background epithelium following Lugol solution
      spraying. The remaining 84% of patients with invasive carcinoma showed normally
      uniform Lugol staining background epithelium. Glycogenic acanthosis was found in
      65 (93%) of 70 patients. CONCLUSIONS: Approximately 80% of patients with
      esophageal squamous cell carcinoma showed normal Lugol staining of background
      epithelium. Field carcinogenesis is postulated to be not predominant in the
      development of esophageal squamous cell carcinoma in our Japanese subjects. In
      contrast, glycogenic acanthosis of the esophagus was associated with the
      background epithelium accompanied with esophageal squamous cell carcinoma.

PMID- 15143902
TI  - Pancreas-sparing duodenectomy in duodenal pathology: indications and results.
AB  - BACKGROUND/AIMS: Pancreas sparing-duodenectomy is an organ-preserving surgical
      procedure suitable for patients with premalignant or early malignant lesions of
      the duodenum. The surgical technique is challenging due to the close anatomical
      relationship between the pancreas and the duodenum. METHODOLOGY: All patients
      undergoing pancreas-sparing duodenectomy for benign or premalignant condition of
      the duodenum operated on between 1998 and 2001 were analyzed prospectively. The
      surgical technique, the hospital course, and complications are described.
      RESULTS: A total of four patients underwent pancreas sparing-duodenectomy. Two
      patients experienced an uncomplicated postoperative course. In one patient, after
      completing the pancreas sparing-duodenectomy, the operation was converted to a
      Whipple procedure after the intraoperative diagnosis of malignant disease in the
      fresh frozen section. One patient had a complicated postoperative course with
      postoperative pancreatitis requiring several reoperations. At follow-up all
      patients are well, free of recurrence and alive. CONCLUSIONS: Pancreas-sparing
      duodenectomy is a challenging surgical technique and requires excellent knowledge
      of the anatomy. Intraoperative fresh-frozen section is mandatory to exclude
      malignant disease. If performed for appropriate indications, pancreas sparing
      duodenectomy offers the potential to preserve the anatomical gastrointestinal
      passage and the integrity of the pancreas.

PMID- 15143896
TI  - Selective suppression of initial cytokine response facilitates liver regeneration
      after extensive hepatectomy in rats.
AB  - BACKGROUND/AIMS: After extensive hepatectomy, the cytokine network plays an
      important role in injury to the remnant liver and subsequent impairment of liver
      regeneration. Tumor necrosis factor alpha (TNF alpha) and interleukin 1beta (IL
      1beta) are thought to be the initial cytokines associated with liver injury as
      well as with regeneration. We investigated the effect of the suppression of these
      cytokines on liver function and on liver regeneration after subtotal hepatectomy
      in rats. METHODOLOGY: Following 90% hepatectomy, rats were divided into two
      groups. Animals in the FR group received intraperitoneal FR167653, a selective
      inhibitor of TNF alpha and IL 1beta, while those in the Control group received
      vehicle only. Liver chemistry and serum levels of TNF alpha and IL-6 were
      measured serially. Liver specimens were obtained 48 hr after surgery and
      regenerative activity assessed by proliferating cell nuclear antigen (PCNA)
      expression and remnant liver weight. RESULTS: The survival rate was significantly
      better in the FR group (76.4+/-11.7 hrs) than in the Control group (26.8+/-4.3
      hrs, p=0.0014). Liver enzyme and blood sugar levels after surgery were higher in
      the FR group compared to the Control group (p=0.03 or less). Changes in serum
      levels of both TNF alpha and IL-6 were suppressed in FR group rats after surgery.
      Microscopically, hepatocellular damage and steatosis was less prominent in FR
      group livers. PCNA labeling index and residual liver weights were higher in the
      FR group (p<0.001). CONCLUSIONS: Following extensive hepatectomy in rats,
      suppression of early cytokine induction improved liver function and facilitated
      liver regeneration. Suppression of selective cytokine responses could allow
      extended liver resection and reduced risk of liver failure.

PMID- 15143903
TI  - Mucosa-associated lymphoid tissue lymphoma of the duodenum: report of a case
      resistant to Helicobacter pylori eradication.
AB  - We present a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the
      duodenum treated with surgical resection. A 64-year-old woman underwent upper
      gastrointestinal endoscopy because of melena. Examinations revealed an ulcer
      forming lesion at the second portion of the duodenum that was diagnosed
      histologically as low-grade MALT lymphoma. We attempted Helicobacter pylori
      eradication therapy, although all the tests revealed negative results for its
      infection. No sign of remission was observed and we performed surgical resection.
      The patient has shown no sign of recurrence at present, 39 months after the
      operation. Duodenal MALT lymphoma is a rare entity. Only 17 cases have been
      reported in the English literature. We summarized the characteristics of the
      disease and tried to figure out differences in comparison with those in the
      stomach, including the involvement of the Helicobacter pylori infection.

PMID- 15143895
TI  - Nissen fundoplication in infants and children: a long-term clinical study.
AB  - BACKGROUND/AIMS: Infants and children who underwent open Nissen fundoplication
      for gastroesophageal reflux disease were retrospectively evaluated to assess the
      success and complications of this operation. METHODOLOGY: Twenty-six
      neurologically normal children (16 boys and 10 girls between 6 months and 11
      years old) underwent Nissen fundoplication for intractable or complicated
      gastroesophageal reflux between October 1982 and February 2002. Before surgery
      and at follow-up visits, all children were subjected to thorough history, barium
      meal study and gastroscopy with multiple esophageal biopsies. The median follow
      up period was 28 months (range: 11 months-19 years). RESULTS: Persistent vomiting
      or regurgitation since birth was the main symptom (24 patients, 92.3%), chest
      symptoms occurred in 5 patients (19.2%), malnutrition and retarded growth were
      found in 4 patients (15.4%), hematemesis and/or melena occurred in 2 patients
      (7.7%) and dysphagia due to esophageal stricture occurred in 4 patients (15.4%).
      There was no mortality. The mean hospital stay was 4.1 days. Twenty-two patients
      (84.6%) had no recurrent reflux. Reflux symptoms recurred in 4 cases (15.4%). One
      of these cases had no evidence of recurrent pathological reflux, 2 cases with
      preoperative stricture developed wrap disruption, recurrent reflux and re
      stricture. Both refused a second operation. The fourth case developed melena and
      reflux esophagitis due to wrap herniation through the hiatus and was successfully
      managed by a second operation. CONCLUSIONS: Nissen fundoplication is an effective
      operation to correct gastroesophageal reflux in infants and children when the
      drug therapy fails. The operation should be done before occurrence of
      complications to decrease the recurrence of reflux.

PMID- 15143904
TI  - Prognostic factors in esophageal cancer.
AB  - BACKGROUND/AIMS: Despite the advances in surgical treatment and the improvements
      in perioperative care for esophageal cancer, the long-term prognosis of this
      disease is poor. To improve long-term survival, it is essential to identify
      prognostic factors. This paper deals with the prognostic factors in esophageal
      cancer after potentially curative resection. Furthermore, correlation of the
      genetic alteration obtained from biopsy specimens with the prognostic factor was
      determined. METHODOLOGY: A total of 102 patients, who underwent transthoracic
      esophagectomy, were retrospectively analyzed. In 18 recent patients, the genetic
      alteration of E-cadherin, cyclin D1, and p16INK4 were evaluated in the biopsy
      specimens. RESULTS: Univariate analysis revealed that the number of metastatic
      lymph nodes and the tumor diameter significantly influenced prognosis. A Cox
      proportional regression hazard model showed that only the number of metastatic
      lymph nodes significantly affected prognosis. Overexpression of E-cadherin and
      amplification of cyclin D1 was correlated with the number of metastatic lymph
      nodes but not with p16INK4. CONCLUSIONS: Preoperative genetic assessment of
      biopsy specimens obtained endoscopically provides useful information concerning
      selection of treatment modalities.

PMID- 15143905
TI  - Cardio-esophageal cancer. Is 18Fluorodeoxyglucose positron emission tomography
      worthwhile?
AB  - BACKGROUND/AIMS: 18Fluorodeoxyglucose positron emission tomography has been
      proposed for the preoperative staging of carcinomas of the esophagus and gastric
      cardia. The aim of this study was to assess its diagnostic value and its
      influence on therapeutical decisions. METHODOLOGY: Twenty-eight patients with a
      cancer of the esophagus or gastric cardia underwent a 18Fluorodeoxyglucose
      positron emission tomography on a gamma camera with coincidence detection
      electronics, in addition to our standard preoperative procedures (barium swallow,
      liver ultrasonography, chest X-ray). Four types of lesions were searched for:
      primary tumor, abdominal and mediastinal lymph nodes, and distant metastases.
      Results of 18Fluorodeoxyglucose positron emission tomography were compared to
      pathological findings. RESULTS: Sensitivity for the primary tumor was 86%.
      Sensitivity for mediastinal and abdominal lymph nodes was 75 and 54%,
      respectively, whereas specificity was 100%. Distant metastases were detected in 4
      patients: liver metastasis in 2 patients and bone metastasis in 2 patients.
      Results of 18Fluorodeoxyglucose positron emission tomography influenced
      therapeutical decisions for 2 patients. CONCLUSIONS: 18Fluorodeoxyglucose
      positron emission tomography seems to be worthwhile in the preoperative staging
      of carcinomas of the esophagus and gastric cardia, mainly because it may detect
      distant metastases.

PMID- 15143907
TI  - Primary adenocarcinoma arising in esophageal colon interposition: report of a
      case.
AB  - Colon interposition has become a favored technique for esophageal reconstruction.
      We report a 79-year-old man with primary adenocarcinoma arising in the interposed
      colon 30 years after esophageal reconstruction for esophageal cancer. The
      occurrence of a carcinoma in a colon removed from its natural location and
      serving a different function suggests this rise in incidence may result from the
      action of carcinogens on colonic cells over an increasing period.

PMID- 15143906
TI  - Variceal recurrence after endoscopic sclerotherapy associated with the
      perforating veins in lower esophagus independently.
AB  - BACKGROUND/AIMS: The perforating veins as a lateral blood supply route for
      esophageal varices in lower esophagus are associated with the recurrence of
      esophageal varices after sclerotherapy, but not vessels at the esophagogastric
      junction as an ascending blood supply route. To date, however, frequency of
      association perforating veins alone with variceal recurrence has not been
      investigated. To clarify the influence of perforating veins alone on variceal
      recurrence after endoscopic injection sclerotherapy, we studied the prevalence of
      variceal recurrence in patients with perforating veins detected by endoscopic
      ultrasonography after treatment. METHODOLOGY: Forty-two patients who underwent
      injection sclerotherapy and received endoscopic ultrasonography after treatment
      to evaluate the effect on the collaterals around the esophagus, were studied.
      Subjects were classified in four groups according to endosonographic findings as
      follows: group A: perforating veins (+) and vessels at esophagogastric junction
      (+), group B: perforating veins (+) and vessels at esophagogastric junction (-),
      group C: perforating veins (-) and vessels at esophagogastric junction (+), group
      D: perforating veins (-) and vessels at esophagogastric junction (-). RESULTS:
      Variceal recurrence was observed in 60% (6/10) of patients in group A, 64.3%
      (9/14) of patients in group B, 33.3% (1/3) of patients in group C, 0% (0/15) of
      patients in group D, respectively. The prevalence of variceal recurrence was
      compared between the 4 groups. No significant difference between group A or C and
      B was noted, and there was a significant difference between group A or B and D.
      CONCLUSIONS: These results suggested that perforating veins are highly associated
      with variceal recurrence after sclerotherapy even if perforating veins are
      independent.

PMID- 15143908
TI  - Mucosa-associated lymphoid tissue lymphoma of the esophagus: case report and
      review of the literature.
AB  - We report the histomorphologic and immunohistochemical features of another case
      of mucosa-associated lymphoid tissue (MALT) lymphoma arising from the esophagus
      and discuss the problems of differential diagnosis. The patient was a 49-year-old
      man, who had no gastrointestinal symptoms. On endoscopy, a smooth-surfaced,
      semibulbous lesion was found 36 cm from the incisors. We performed radical
      resection of this submucosal tumor with video-assisted thoracoscopic surgery for
      the purpose of diagnosis and treatment. The immunophenotype of the centrocyte
      like-cells was CD20+, BCL2+, CD5-, CD10-, CD23- CD45RO- and cyclin D1-. Diffuse
      immunostaining of bcl-2 was detected in the nuclei of the tumor cells without
      lymph follicles. Southern blotting analyses of the IgH gene detected a single
      dominant band indicative of a clonal IgH rearrangement. From the pathological,
      immunohistochemical, and molecular biological features we concluded that the
      tumor was a MALT lymphoma. Only three cases of primary esophageal MALT lymphoma
      have been reported to date. On the basis of the present case and the three
      previously reported cases, we suggest that MALT lymphoma of the esophagus is
      usually an elevated type. The spectrum of sites in which gastrointestinal MALT
      lymphoma occurs should be expanded to include the esophagus.

PMID- 15143909
TI  - Surgical repair of esophagobronchial fistula caused by radiation injury.
AB  - We present an unusual case of a benign esophagobronchial fistula caused by
      radiotherapy to treat esophageal carcinoma which was closed successfully. A 62
      year-old man with superficial squamous cell carcinoma of the esophagus underwent
      radiotherapy, including 60 Gy externally and 10 Gy intraluminally from January to
      March 1995. Esophagography revealed a fistula between the esophagus and left main
      stem bronchus on January 14, 1996. No residual cancer existed. Neither stenting
      with a silicone tube nor with a covered flexible metallic stent occluded the
      fistula. Thoracic esophagectomy, closure of the esophagobronchial fistula using a
      2-cm nubbin of esophageal wall, surrounding the orifice of the fistula and
      antesternal gastric pull-through reconstruction with mediastinal lymphadenectomy
      were performed. The postoperative course was uneventful and there is no evidence
      of recurrence of the fistula or the cancer 5 years postoperatively. Radiotherapy
      may cause esophagobronchial fistula even in cases of superficial esophageal
      cancer. Bypass surgery should be considered because stenting is not effective for
      benign fistula without stricture.

PMID- 15143911
TI  - Gastrointestinal adverse reactions following anthrax vaccination: an analysis of
      the Vaccine Adverse Events Reporting System (VAERS) database.
AB  - BACKGROUND/AIMS: The Institute of Medicine (IOM) of the United States Academy of
      Sciences in 2000 encouraged the evaluation of active long-term monitoring studies
      of large populations to further evaluate the relative safety of anthrax vaccine.
      Anthrax is a deadly bacterial infectious disease that currently has been
      engineered as a biological warfare agent. The vaccine produced against anthrax is
      a cell-free crude culture of the various toxin components of the natural disease.
      The U.S. military current goal is to vaccinate its entire personnel by 2003. The
      purpose of this study was to evaluate anthrax vaccination and its association
      with arthritic, immunological and gastrointestinal adverse reactions based upon
      analysis of the Vaccine Adverse Events Reporting System (VAERS) database.
      METHODOLOGY: We analyzed the VAERS database from 15 December 1997 to 12 April
      2000. We also compared the incidence of anthrax adverse reactions with the
      incidence of adverse reactions reported to VAERS after adult tetanus vaccination.
      RESULTS: Anthrax vaccine was one of the most reactogenic vaccines included in
      VAERS. The incidence of adverse reactions reported following anthrax vaccine was
      higher for every reaction analyzed in comparison to the adult vaccine control
      groups. CONCLUSIONS: The current anthrax vaccine may be acceptable in military
      populations in impending threat of anthrax exposure, the cost-benefits of
      vaccination in less high risk military populations may be more questionable.
      Civilian anthrax vaccination will require a less reactogenic vaccine. Civilian
      doctors should be aware of anthrax vaccine adverse reactions. Military and
      civilian doctors should also be diligent in their reporting to VAERS of cases of
      adverse reactions to anthrax vaccine.

PMID- 15143910
TI  - Stress ulcer prophylaxis in critically ill patients: a randomized controlled
      trial.
AB  - BACKGROUND/AIMS: Critically ill patients especially who require mechanical
      ventilation or have coagulopathy are at increased risk for stress-related
      gastrointestinal hemorrhage. There are conflicting data on the efficacy and
      complication rates of various prophylactic regimens. METHODOLOGY: Our single
      center randomized, placebo-controlled study included 287 patients with high risk
      for stress-related upper gastrointestinal hemorrhage (>48 h mechanical
      ventilation, coagulopathy). We compared 3 prophylactic regimens (proton pump
      inhibitor--omeprazole 40 mg i.v. once daily, n=72; H2 antagonists--famotidine 40
      mg twice a day, n=71; and sucralfate 1 g every 6 hours, n=69) with placebo (n=75)
      in patients with trauma or after major surgery. RESULTS: Of 287 assessable
      patients, clinically significant stress-related upper gastrointestinal bleeding
      was observed in 1%, 3%, 4%, and 1% of patients assigned to receive omeprazole,
      famotidine, sucralfate, and placebo, respectively (p>0.28). Bleeding developed
      significantly more often in patients with coagulopathy compared with the others
      (10% vs. 2%; p=0.006). The gastric pH (p>0.001) and gastric colonization (p<0.05)
      was significantly higher in the patients who received pH increasing substances
      when compared with the other 2 groups. Nosocomial pneumonia occurred in 11% of
      patients receiving omeprazole, in 10% of famotidine patients, in 9% of sucralfate
      patients and in 7% of controls (p>0.34). No statistically significant differences
      were found for days on ventilator, length of ICU stay, or mortality among all the
      4 groups. CONCLUSIONS: We could not show that omeprazole, famotidine, or
      sucralfate prophylaxis can affect already very low incidence of clinically
      important stress-related bleeding in high-risk surgical intensive care unit
      patients. Furthermore, our data suggested that especially gastric pH increasing
      medication could increase the risk for nosocomial pneumonia. Routine prophylaxis
      for stress-related bleeding even in high-risk patients seems not to be justified.

PMID- 15143913
TI  - Two cases of ileosigmoid knot: the youngest reported patient and CT findings.
AB  - Ileosigmoid knot is one of the causes of intestinal obstruction, but it is very
      difficult to make a correct preoperative diagnosis of the disease. This rare
      condition with high mortality is usually found in adult patients and has rarely
      been reported in children. We recently experienced two patients with ileosigmoid
      knot. One was a 4-year-old boy and the other a 60-year-old man. Both patients had
      suffered the sudden onset of abdominal pain. The boy was in a state of shock on
      admission. Abdominal computed tomography findings indicated intestinal
      obstruction. In laparotomy, intestinal resection and detorsion without resection
      were performed for the boy and adult patients, respectively. We herein report a
      case of ileosigmoid knot in which the patient was the youngest reported in the
      English literature, and showed that the computed tomography examination provided
      valuable information in both patients.

PMID- 15143912
TI  - Ulcerative colitis: analyses of 116 cases (do extraintestinal manifestations
      effect the time to catch remission?).
AB  - BACKGROUND/AIMS: Evaluation of clinical, demographic and epidemiologic features
      of ulcerative colitis and therapy response of these patients. METHODOLOGY:
      Retrospectively, 116 patients (64.7% female) were enrolled in this study. Mean
      age and mean follow-up period were 36+/-16, 5+/-2 years, respectively. RESULTS:
      The most common anatomic involvement was pancolitis (60.3%) and the others were
      as follows: left side 25%, rectum 13.8% and ileum (backwash ileitis) 0.9%.
      Extraintestinal manifestations were observed in 42.2% of patients (sacroiliitis
      12%, primary sclerosing cholangitis 7.6%, pyoderma gangrenosum 2.4%, peripheral
      arthropathy 1.6%, autoimmune hepatitis 1.6%, steatosis 12.9%, gallstone 0.8%,
      perianal fistulas 0.8%, sagittal sinus thrombosis 0.8%, psoriasis 0.8%). Multiple
      extraintestinal manifestations were observed (primary sclerosing cholangitis +
      pyoderma gangrenosum) in 2 patients. Colonic perforation due to toxic megacolon
      was observed in only one patient during follow-up period. The mean period for
      remission was 3.7 months in 72% of patients with pancolitis by the treatment of 5
      aminosalicylic acid (5-ASA) (2-3 gr/day) + methylprednisolone (1 mg/kg/day) +/-
      (for maintenance of remission) azathioprine (AZT) (1.5-2 mg/kg/day); 3.7 months
      in 72% of left-sided colitis by 5-ASA +/- corticosteroid enemas +/-
      methylprednisolone (1 mg/kg/day) +/- (for maintenance of remission) AZT (1.5-2
      mg/kg/day) and 3.7 months in 62.5% of patients with distal colitis by 5-ASA (p.o.
      +/- enema) +/- corticosteroid enemas. Colectomy was performed on 7 patients
      refractory to these treatments. Six patients (4 of them had pancolitis) were
      treated with cyclosporine (Cys) (4 mg/kg/day, p.o.). Only one patient, a non
      responder to Cys therapy, had colectomy. The mean remission time was 4.7 months
      in 80.6% of patients with extraintestinal involvement and 3.2 months in 71.2% of
      patients without extraintestinal involvement (P=0.002). CONCLUSIONS: Medical
      therapy was generally enough for the treatment. Cys and/or surgery can be another
      choice for the patients that do not respond to the medical therapy.
      Extraintestinal manifestations do not change the remission rate, but prolong the
      time to catch remission.

PMID- 15143914
TI  - An extensive metabolizer with recurrent ulcer responding to high dose of
      lansoprazole.
AB  - A 51-year-old man underwent surgery for duodenal ulcer in 1983. Ulcer recurred
      several times. Recently, the patient was receiving 30 mg/day of lansoprazole. On
      June 15, 2001 hemorrhagic recurrent ulcer was diagnosed. Analysis of CYP2C19
      enzyme genotype indicated that the patient was a heterozygous extensive
      metabolizer, suggesting that 30 mg/day of lansoprazole did not produce effective
      concentrations of drug in the serum. The dose of lansoprazole was increased to 60
      mg/day, and intragastric pH monitoring revealed that a pH > or = 3 was maintained
      for 99.8% of a 24-hour period, as compared with a previous value of 88.3%. After
      3 weeks of treatment, endoscopic examination showed that a red scar had formed at
      the ulcer site.

PMID- 15143915
TI  - Serum markers of liver fibrosis and histologic severity of fibrosis in resected
      liver.
AB  - BACKGROUND/AIMS: Serum concentrations of the 7S fragment of type IV collagen (7S
      collagen), amino-terminal propeptide of type III procollagen (PIIIP), and
      hyaluronic acid (HA) have been reported to serve as serologic markers of liver
      fibrosis in hepatitis and cirrhosis. We investigated whether these fibrosis
      markers reliably reflect histologic changes in the livers of patients with
      hepatocellular carcinoma. METHODOLOGY: Subjects included 165 patients undergoing
      liver resection for hepatocellular carcinoma. Most were seropositive for chronic
      hepatitis B or C. Histopathologic changes in liver tissue resected with the tumor
      were scored according to Knodell's histologic activity index. Serum was sampled
      for assays shortly before surgery. RESULTS: Significant correlations were found
      between hepatitis activity score and 7S collagen, PIIIP, and HA. Concentrations
      of 7S collagen differed significantly between activity grades, but differences
      were not significant for PIIIP or HA. Significant correlations were found between
      fibrosis staging score and all these three markers. When patients were divided
      according to activity grade, 7S collagen showed stronger correlation with
      fibrosis staging score than did PIIIP or HA. CONCLUSIONS: The 7S collagen
      fragment correlated more strongly than PIIIP or HA with stage and activity grade
      in patients with hepatocellular carcinoma. However, overlapping of results
      between histologically defined groups appeared to limit clinical diagnostic
      usefulness of all markers in individual patients.

PMID- 15143916
TI  - Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon
      (133Xe) clearance.
AB  - BACKGROUND/AIMS: The aim of the present study was to identify in a standardized
      experimental rat liver tumor system the drugs which are most appropriate in
      influencing the relationship between liver tumor and normal liver parenchyma
      blood flow as estimated with 133Xe washout clearance method, and thereby
      positively influencing the kinetics of chemotherapeutic drugs. A battery of
      vasoactive drugs, which according to a literature review were considered to be
      active, were tested. METHODOLOGY: Twelve drugs were administered intravenously on
      113 Wistar-Fu rats with an experimental adenocarcinoma in the liver (weight 0.62
      g). 133Xe was applied in the tumor and in normal parenchyma with and without
      administration of a vasoactive drug. The pulses were registered with a NaI (Tl)
      scintillation detector connected to a multichannel analyzer. The disappearance
      rate of the isotope was calculated according to a single compartment model. Four
      recordings were performed in each rat randomly in tumor and liver parenchyma with
      and without a drug (series A) and one series twice in tumor and twice in
      parenchyma with a drug (series B). RESULTS: In unaffected animals the tumor to
      liver quotient was 0.57+/-0.35. This quotient was higher in tumors less than 0.53
      g. Angiotensin-II 8 mg i.v. increased the quotient to 0.95+/-0.20. No other drug
      significantly influenced the quotient. CONCLUSIONS: In an experimental
      adenocarcinoma in the liver this study has investigated the possibility of
      increasing the tumor to normal liver parenchyma blood flow quotient by a variety
      of vasoactive substances for the beneficial modification of tumor blood flow.
      Angiotensin II 8 mg i.v. was the only drug, which increased the quotient. None of
      the other tested drugs were supporting previous presented results on influencing
      tumor blood flow.

PMID- 15143917
TI  - Hypothalamo-pituitary gonadal axis in men with chronic hepatitis.
AB  - BACKGROUND/AIMS: Hypothalamo-pituitary function of male patients with chronic
      active hepatitis was evaluated. The effects of interferon alpha therapy on
      hypothalamo-pituitary-gonadal axis were also investigated. METHODOLOGY: Twenty
      patients with chronic B and C hepatitis, and 10 healthy subjects were studied.
      Before and after treatment with IFN alpha, basal levels of FSH, and LH were
      obtained and all groups were evaluated with LH-RH stimulation test. RESULTS:
      Baseline hormone levels and FSH and LH responses to LH-RH stimulation test were
      similar in patients and controls. It was notable that the LH response was
      considerably greater than that of FSH and pretreatment FSH results in patients
      with HCV infection appeared earlier than those of patients with HBV infection.
      Following IFN alpha treatment, the results of LH-RH stimulation test were similar
      to those of controls but there were a delayed LH and FSH response to LH-RH
      stimulation test. CONCLUSIONS: Hypothalamic and/or gonadal hypogonadism is
      correlated with the degree of liver damage in cirrhosis. In patients with chronic
      hepatitis, which is characterized by lesser degree of liver damage than
      cirrhosis, HPG axis is not affected. IFN alpha, still in use for treatment of
      hepatitis, did not have any effect on HPG axis although it has many side effects.

PMID- 15143918
TI  - Interspousal transmission of hepatitis C virus: application of comparing the
      variability of HVR1 nucleotide region.
AB  - BACKGROUND/AIMS: The interspousal transmission of hepatitis C virus (HCV) has
      been a controversial issue in previous studies. We thus aim to investigate the
      possibility of HCV transmission between spouses by comparing the variability of
      HCV hypervariable region 1 (HVR1) between spouses and non-spouses. METHODOLOGY:
      Four spouses both positive for anti-HCV antibody and HCV RNA were enrolled in our
      study. Reverse transcriptional polymerase chain reaction (PCR) of HVR1 region was
      done from each patient for blood samples. The amplified PCR products were
      molecularly cloned, and eight to ten clones from each patient were analyzed. In
      addition to the phylogenetic analysis, comparing the variability of nucleotide
      and deduced amino acid sequences of HVR1 and outside HVR1 from these clones by a
      computer software program PHYLIP version 3.57 was performed in each patient,
      between spouse and among non-family patients. RESULTS: All eight patients were
      infected with genotype Ib HCV. The sequences of eight to ten clones of HCV HVR1
      in each patient showed quasispecies nature of HCV. Moreover, the variabilities of
      nucleotide sequence and deduced amino acid sequence of HVR1 were much higher than
      those outside of HVR1. Between spouses, the variabilities of HVR1 were
      significantly lower (p<0.001) than those of non-family members in 3 of 4
      families. Clones of the same patient displayed the closest relationship in the
      phylogenetic tree. In addition, spouses of three families showed a closer
      relationship than other non-family patients. CONCLUSIONS: This study strongly
      suggests that sexual transmission does exist, which can be confirmed by comparing
      the variability of HVR1 nucleotide region of HCV.

PMID- 15143919
TI  - Telomerase activity and telomerase catalytic subunit in hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Telomerase activation has been found in most malignant tumors.
      Human telomerase reverse transcriptase is a catalytic subunit of human telomerase
      and a rate-limiting factor of the enzymatic activity of telomerase. The present
      study was designed to examine the usefulness of detecting human telomerase
      catalytic subunit mRNA and telomerase activity as a molecular diagnostic marker
      for human liver cancers. METHODOLOGY: Thirty-one specimens of hepatocellular
      carcinoma and corresponding adjacent tissues were analyzed for human telomerase
      reverse transcriptase expression by reverse transcription polymerase chain
      reaction and for telomerase activity by polymerase chain reaction-based telomeric
      repeat amplification protocol. RESULTS: Human telomerase reverse transcriptase
      mRNA expression was observed in 97% of hepatocellular carcinoma tissues, in
      contrast none of the non-tumorous liver tissues did. Telomerase activity was
      detected in 94% of hepatocellular carcinoma and in only 16% of adjacent liver
      tissues. Human telomerase reverse transcriptase mRNA expression and telomerase
      activity were observed in all 3 grade I (well-differentiated) hepatocellular
      carcinoma. Significant correlations between human telomerase reverse
      transcriptase mRNA expression and hepatocellular carcinoma and also between
      telomerase activity and HCC were found (both p<0.001). CONCLUSIONS: The results
      indicate that human telomerase catalytic subunit mRNA expression and telomerase
      activity might be associated with hepatocellular carcinogenesis and could be as
      markers for diagnosis of hepatocellular carcinoma.

PMID- 15143921
TI  - Mobilization of peripheral blood hematopoietic stem cells following liver
      resection surgery.
AB  - BACKGROUND/AIMS: Stem cells are characterized by plasticity, namely the ability
      of interchanging between various tissue and organs. In this regard, many studies
      have demonstrated the presence of antigenic structures relevant to the
      hematopoietic stem cell on hepatocytes, thus suggesting that in certain
      conditions liver cells may derive from the hematopoietic compartment. The aim of
      this study has been to verify whether surgical liver resection can activate bone
      marrow, by mobilizing peripheral blood hematopoietic stem cells (CD34+ cells)
      putatively able to induce liver repopulation. METHODOLOGY: White blood cell and
      CD34+ cell count was determined at baseline (before surgery) and then monitored
      in the postoperative period in 13 patients undergoing liver resection (in most
      cases because of malignant, primary or secondary liver diseases) and, as a
      control group, in 12 patients affected with other diseases requiring abdominal
      surgery, but not liver resection. Moreover, to assess the basal value of
      circulating CD34+ cells, 50 healthy blood donors were included in the study. The
      CD34+ cell count has been carried out by flow cytometry, by applying conventional
      protocols. RESULTS: Patients, as altogether considered, showed at baseline a
      significantly higher white blood cell count as compared to healthy controls
      (7.41+/-2.89 x 10(3)/microL vs. 6.00+/-1.37 x 10(3)/microL, P<0.01), as opposed
      to the CD34+ cell count, the results of which were significantly lower (2.8+/
      1.8/microL vs. 4.1+/-1.9/microL, P<0.01). The increase of CD34+ cells was
      significantly higher in patients following liver resection as compared to others
      (+6.5+/-4.1/microL vs. +0.7+/-1.4/microL, P<0.001), whereas the variation of
      white blood cell count was not statistically significant (+1.87+/-3.76 x
      10(3)/microL vs. + 1.51+/-2.87 x 10(3)/microL). CONCLUSIONS: Our results indicate
      that hepatic injury caused by extensive liver resection may constitute a trigger
      to the mobilization of hematopoietic stem cells putatively able to differentiate
      into hepatocytes, thus starting the recovery process of liver. These data could
      open innovative views to the treatment of certain liver diseases (e.g. fulminant
      hepatic failure), in particular by the administration of hematopoietic growth
      factors, such as G-CSF or GM-CSF, after the hepatic damage, to contribute,
      through the activation of the hematopoietic compartment, to a more efficient
      liver regeneration.

PMID- 15143920
TI  - Hepatocellular carcinoma with bile duct thrombi: analysis of surgical treatment.
AB  - BACKGROUND/AIMS: To summarize the experience of surgical intervention for
      hepatocellular carcinoma with bile duct thrombi, and to evaluate the influence on
      prognosis. METHODOLOGY: From 1994 to 2002, 15 patients with hepatocellular
      carcinoma and bile duct thrombi who underwent surgical intervention were
      retrospectively analyzed. The operative procedures included hepatectomy with
      removal of bile duct thrombi (n=7), hepatectomy combined with extrahepatic bile
      duct resection (n=4), thrombectomy through choledochotomy (n=3), and piggyback
      orthotopic liver transplantation (n=1). RESULTS: The 1- and 3-year survival rates
      were 73.3% and 40%, respectively. Two patients survived over 5 years. There were
      no significant differences in the survival rates between patients with and
      without obstructive jaundice (P>0.05). The survival rate of patients with portal
      vein invasion was significantly lower than for those without portal vein invasion
      (P<0.05). CONCLUSIONS: Surgical intervention was effective for patients with
      hepatocellular carcinoma and bile duct thrombi. Operation for recurrent
      intrahepatic tumor can prolong the survival period. Liver transplantation is a
      new operative procedure worthy of investigation.

PMID- 15143923
TI  - Phase II study of combination doxorubicin, interferon-alpha, and high-dose
      tamoxifen treatment for advanced hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Our previous studies showed that high-dose tamoxifen may improve
      the therapeutic efficacy of doxorubicin (HTD regimen) in hepatocellular
      carcinoma. Interferon-alpha, either as a single-agent treatment or as a
      biochemical modulator, has also been reported to be effective in the treatment of
      hepatocellular carcinoma. In this study, we sought to clarify if the addition of
      Interferon-alpha2b to HTD regimen could further improve the control of advanced
      hepatocellular carcinoma. METHODOLOGY: Eligible patients had unresectable and non
      embolizable hepatocellular carcinoma, objectively measurable tumors, adequate
      hemogram and major organ function, age > or = 75 year, and a Karnofsky
      performance status > or = 60%. The treatment included oral tamoxifen 40 mg/m2,
      q.i.d., Day 1-7; interferon-alpha2b subcutaneous injection, 5 MU/m2, q.d. (Day 3
      5) and 3 MU/m2, q.o.d. (Day 6-21); and intravenous doxorubicin 60 mg/m2, Day 4,
      repeated every 4 weeks. RESULTS: From May 1997 through July 2002, a total of 30
      patients were enrolled, 25 of whom were eligible for assessment of response and
      toxicity. These included 20 men and 5 women, with a median age of 45 years. They
      received an average of 3.5 (range: 1-8) courses of chemotherapy. Grade 3-4
      leukopenia and Grade 3-4 thrombocytopenia developed in 46.7% and 51.0% of
      treatment courses, respectively. Gastrointestinal toxicity was generally mild.
      One patient achieved a complete remission and remained disease-free at this
      report, with a progression-free survival of 49 months at last follow-up in
      September 2002. Five patients achieved a partial remission, with a median
      progression-free survival of 7 months. The total response rate was 24% (95%
      confidence interval 9.4-45.1%). Median survival for all 25 patients was 6.0
      months and the 1-year survival rate was 16%. CONCLUSIONS: Combination of
      interferon-alpha2b, high-dose tamoxifen, and doxorubicin is an effective
      treatment for advanced hepatocellular carcinoma. However, the data does not
      support that addition of interferon-alpha2b is superior to HTD regimen alone.

PMID- 15143924
TI  - Limited resection of the right hemiliver based on reclassification of the right
      anterior segment of the liver.
AB  - We proposed that the anterior segment was divided into ventral and dorsal
      segments, and reclassified the right hemiliver into three segments; ventral,
      dorsal, and posterior segments. According to our classification we successfully
      performed limited resection of the right hemiliver.

PMID- 15143922
TI  - Fibronectin levels in chronic viral hepatitis and response of this protein to
      interferon therapy.
AB  - BACKGROUND/AIMS: In this study, the plasma fibronectin levels in the cases of
      chronic hepatitis B and C infection and this protein's response to the interferon
      therapy were examined. METHODOLOGY: Totally, 38 patients with chronic hepatitis,
      21 of them being hepatitis B, 17 of them being hepatitis C; and 24 healthy blood
      donors, as the control group, took part in this study. The quantitative
      determinations of fibronectin in plasma samples were performed with the Bohring
      Nephelometer BN 100 (N Antiserum to Human Fibronectin, code no OUND, Dade Behring
      Marburg GmbH, Marburg Germany). RESULTS: It was observed that the fibronectin
      plasma levels of the control group were significantly higher than those of the
      patient group before the therapy (p=0.043). After the interferon therapy of six
      months, the difference between the fibronectin levels of 16 examined patients
      before and after the treatment was found to be significant (p=0.001). A negative
      correlation was detected between the fibronectin levels before the therapy and
      the inflammatory grade as far as the histopathology of the illness was concerned
      (r=-0.49), which is a statically significant value (p=0.002). The correlation
      between the levels of fibronectin and the stage of the fibrosis was found to be
      insignificant statistically (p=0.225). When comparing the levels before and after
      the therapy, as far as ALT and AST values were concerned, it was observed that
      both parameters fell significantly after the therapy (p=0.002). However, no
      correlation was observed between the fibronectin levels and ALT, AST before and
      after the therapy. CONCLUSIONS: Fibronectin can be a useful marker for showing
      the hepatic inflammation and damage in the cases of chronic hepatitis, and can
      also be used in the evaluation of the response to the interferon therapy like
      other biochemical parameters (ALT, prothrombin activity etc.).

PMID- 15143925
TI  - Living-related liver transplantation in a patient with end-stage hepatolithiasis
      and a biliary-bronchial fistula.
AB  - Liver transplantation in patients with end-stage hepatolithiasis is complicated
      by the high incidence of the suppurative cholangitis and systemic infection. A 43
      year-old Korean-Japanese woman with hepatolithiasis, biliary cirrhosis,
      suppurative cholangitis, and biliary-bronchial fistula underwent living-related
      liver transplantation (LRLT) using a right lobe graft of her sister. The risk of
      infection was minimized by preoperative percutaneous transhepatic biliary
      drainage initiated 2 months before transplantation. The native liver was resected
      en bloc with the extrahepatic bile ducts and the infected section of the right
      hemidiaphragm. Opportunistic infection was prevented by limiting antimicrobial
      therapy to the interval from preoperative day 3 to postoperative day 4.
      Immunosuppressive agents were given below standard dose. The postoperative course
      following LRLT was uncomplicated, and hepatic function was good. Careful
      management of infection and adequate graft size are essential for successful LRLT
      in patients with end-stage hepatolithiasis.

PMID- 15143927
TI  - Serotonin release during percutaneous radiofrequency ablation in a patient with
      symptomatic liver metastases of a neuroendocrine tumor.
AB  - In a patient with symptomatic liver metastases of a neuroendocrine tumor larger
      than 10 cm in diameter percutaneous radiofrequency ablation was performed. The
      ablation resulted in a significant decrease in tumor size and a good long-term
      improvement of symptoms. Plasma serotonin 48 hours after the ablation was
      approximately 10-fold lower than before. However, sequential determination of
      plasma serotonin during the radiofrequency ablation revealed a two-fold increase
      of plasma serotonin induced by the procedure. There was also an approximately
      three-fold increase of 5-hydroxyindol acetic acid in urine in the 24 hours
      following the ablation. The data show that ablation procedures in neuroendocrine
      tumors may induce hormone release which may be critical in patients with severe
      clinical symptoms.

PMID- 15143926
TI  - Repeated resections of extrahepatic metastases after hepatic resection: an
      aggressive approach to hepatocellular carcinoma.
AB  - Survival following curative hepatic resection for hepatocellular carcinoma is
      limited by a high incidence of recurrence. Resection of extrahepatic recurrences
      has been shown to prolong survival in selected patients. We report two cases in
      whom repeated resections of extrahepatic metastases achieved good palliation and
      survival. The first patient had cerebral, pulmonary and splenic metastases that
      appeared more than four years following an extended left hepatectomy for a 4-cm
      hepatocellular carcinoma. Resection of the metastases in the three organs was
      performed in sequence, and the patient remained alive and asymptomatic 12 months
      after the metastatic recurrence. The second patient developed pulmonary
      metastases after an extended right hepatectomy for a 16-cm hepatocellular
      carcinoma. Following two resections of pulmonary metastases, he was alive and
      disease-free for seven years. These two cases illustrate that an aggressive
      surgical approach of repeated resections of extrahepatic recurrences after
      curative resection of hepatocellular carcinoma can result in long-term survival
      in selected patients.

PMID- 15143929
TI  - Resection and radiofrequency ablation of multiple liver adenomas secondary to
      anti-conceptive pills.
AB  - A case of multiple hepatic adenomas associated with birth control pills in a 25
      year-old female is presented. Her only complaint was abdominal pain, and an
      elevated alkaline phosphatase was the only laboratory abnormality. The largest
      adenoma was located in the caudate lobe and was resected. The other two were
      small, located deep in the right lobe, and treated with radiofrequency ablation.
      Currently, the patient is asymptomatic and her alkaline phosphatase has returned
      to normal levels.

PMID- 15143928
TI  - Hepatocellular carcinoma in a case of Dubin-Johnson syndrome treated successfully
      with a central bilateral segmentectomy.
AB  - A 72-year-old woman with hepatocellular carcinoma and HCV cirrhosis combined with
      Dubin-Johnson syndrome was successfully treated by a central bilateral
      segmentectomy. While the preoperative serum bilirubin level is one of the
      established criteria for determining the indications for a hepatic resection, it
      is not effective for HCV cirrhosis cases associated with Dubin-Johnson syndrome.
      Postoperative hyperbilirubinemia may be cured without special treatment such as
      bilirubin absorption or plasma exchange, but such patients must be carefully
      observed to ensure that liver failure does not occur.

PMID- 15143931
TI  - Non-pancreatic periampullary adenocarcinomas: an explanation for favorable
      prognosis.
AB  - BACKGROUND/AIMS: Our previous studies demonstrate that patients with non
      pancreatic periampullary adenocarcinomas have a favorable prognosis relative to
      those with pancreatic adenocarcinoma. This study investigates histopathologic
      factors that contribute to the superior outcome of these patients. METHODOLOGY: A
      retrospective review of all patients explored for periampullary neoplasms at a
      single institution over a 20-year period. RESULTS: 291 patients with
      periampullary neoplasms underwent exploratory laparotomy, of which 185 had
      resectable tumors. Periampullary adenocarcinomas were resected in 120: pancreatic
      head (n=74), distal common bile duct (n=10), duodenum (n=5), and ampulla of Vater
      (n=31). The resection rate for non-pancreatic adenocarcinomas was 90%, while that
      of pancreatic cancers was 44% (p<0.01). Median survival for resected non
      pancreatic adenocarcinomas was 38.8 months; that of pancreatic tumors was 15.3
      months (p<0.01). Non-pancreatic adenocarcinomas were significantly smaller
      (p<0.001), better differentiated (p<0.001), and less likely to have involved
      nodes (p<0.001), margins (p<0.001), perineural invasion (p<0.001), or vascular
      invasion (p<0.2) than pancreatic adenocarcinomas. CONCLUSIONS: Histopathologic
      features of non-pancreatic periampullary adenocarcinomas significantly
      differentiate them from pancreatic adenocarcinoma and contribute to their
      relatively favorable long-term outcome following resection.

PMID- 15143933
TI  - Heterotopic pancreas--clinical presentation and pathology with review of the
      literature.
AB  - BACKGROUND/AIMS: Heterotopic pancreas is usually a silent gastrointestinal
      malformation, but it may become clinically evident when complicated by chronic
      inflammation or by growth. METHODOLOGY: We report on eleven cases of heterotopic
      pancreatic tissue. The cases were selected from the records of our Surgical
      Department and Institute of Pathology. The literature about heterotopic pancreas
      is reviewed. RESULTS: Nausea and vomiting (27%), epigastric pain (27%),
      ulceration (27%) and weight loss (18%) were the three most frequent symptoms and
      signs. The lesions were diagnosed as gastrointestinal tumor or ulcer by
      gastroduodenoscopy (36%). The other patients were diagnosed during surgery (64%).
      Definitive diagnosis was only achievable by pathology. Heterotopic pancreas was
      the reason for surgery in 36% of the cases, in another 45% diagnosis was
      incidental during surgery and in 18% the diagnosis was established endoscopically
      and surgery was not necessary. CONCLUSIONS: The diagnosis of heterotopic pancreas
      is rarely established, most cases remain clinically silent. In symptomatic
      patients diagnosis should to be secured histologically to exclude malignant
      disease.

PMID- 15143935
TI  - Pancreatic cancer today.
AB  - Carcinoma of the exocrine pancreas remains a challenging disease with poor
      prognosis mainly due to advanced stage by the time of presentation, the early
      systemic dissemination and its extraordinary local tumor progression. Surgery has
      little more to offer in improvement of curative percentage of disease and some
      progress has been made in the medical management of pancreatic cancer with the
      introduction and use of new chemical agents and with combined immunochemotherapy
      and chemoradiotherapy. The purpose of this review article is to focus on all
      recent advances in the management of pancreatic cancer. We review the current
      trial literature emphasizing the risk factors, the molecular biology of the
      tumor, and the therapeutic approach.

PMID- 15143934
TI  - Total papillectomy for borderline malignant tumor of papilla of Vater.
AB  - The therapies for treating tumors of the papilla of Vater remain controversial
      because accurate preoperative diagnosis is difficult. Treatments include
      endoscopic resection, pancreaticoduodenectomy and total papillectomy. We report
      the case of a 69-year-old man who underwent total papillectomy for a borderline
      malignant tumor of the papilla of Vater. In our institution, the decision to
      perform a total papillectomy for borderline malignant adenoma is based on whether
      it is intestinal type or pancreaticobiliary type. Carcinoma of the papilla of
      Vater is classified into two types: an intestinal type and a pancreaticobiliary
      type and the prognosis of the intestinal type is much better than that of the
      pancreaticobiliary type. We suggest that total papillectomy can be performed for
      an intestinal, borderline malignant tumor.

PMID- 15143932
TI  - Platelets counts closely correlate with the disease-free survival interval of
      pancreatic cancer patients.
AB  - BACKGROUND/AIMS: We investigated the relationship between preoperative platelets
      count and the outcome of pancreatic cancer patients. METHODOLOGY: We
      retrospectively reviewed the clinical records of 105 patients with invasive
      ductal carcinoma of the pancreas who underwent radical resection at our
      institution over a 20-year period. The patients were divided into two groups
      based on their preoperative platelets counts: a group with thrombocytosis (> or =
      40x10(4)/mL) and a group with non-elevated platelets counts (< 40x10(4)/mL).
      Histopathological findings, survival rates, recurrence patterns, and disease-free
      survival intervals were compared between the two groups. RESULTS: The outcome of
      the group with thrombocytosis was significantly poorer than that of the group
      with non-elevated platelets counts (p=0.043). The mean disease-free interval of
      patients with thrombocytosis was 4.9 months as opposed to 46.5 months for those
      with non-elevated platelets counts (p=0.006). Patients were classified into four
      groups according to changes in platelets counts after surgery. Consistently, the
      outcome of the group with both pre- and postoperative non-elevated platelets
      counts was the best compared to groups with post- and/or postoperative
      thrombocytosis. CONCLUSIONS: Our clinical data suggest that high platelets counts
      in the preoperative and postoperative period may be associated with a poor
      outcome and shortening of postoperative disease-free survival interval.

PMID- 15143930
TI  - A mixed hepatocellular carcinoma and cholangiocarcinoma: dual expression of
      biliary-type cytokeratin and hepatocyte specific marker.
AB  - A 5-cm lesion in the right hepatic lobe was detected in a 61-year-old man with
      chronic hepatitis C by ultrasonography. Contrast-enhanced computed tomography
      showed a low-density lesion with wide peripheral enhancement. Hepatic angiography
      revealed that the tumor had partial hypervascularity. Although serum
      concentrations of alpha-fetoprotein and carcinoembryonic antigen were within
      normal limits, an elevated concentration of carcinohydrate antigen 19-9 was
      detected in serum. A definitive diagnosis was not made although we strongly
      suspected mixed hepatocellular carcinoma and cholangiocarcinoma. Since
      intraoperative frozen-section examination revealed adenocarcinoma, a right
      hepatic lobectomy with regional lymph node dissection was performed. A histologic
      diagnosis of mixed hepatocellular carcinoma and cholangiocarcinoma was made
      because the hepatic tumor consisted of components of both hepatocellular
      carcinoma and cholangiocellular carcinoma, with a transitional area.
      Additionally, immunohistochemical examination revealed that some tumor cells in
      the transitional area were immunoreactive for both cytokeratin 19 and hepatocyte
      paraffin 1.

PMID- 15143940
TI  - Prophylactic lymph node dissection for early gastric cancer invading submucosa.
AB  - BACKGROUND/AIMS: Prophylactic lymph node dissection for gastric cancer patients
      was considered to prolong survival time and D2 lymph node dissection was a
      standard treatment for early gastric cancer invading submucosa without lymph node
      metastasis. We investigated the possibility of minimizing the extent of
      prophylactic lymph node dissection for early gastric cancer invading submucosa if
      there was no evidence of lymph node metastasis. METHODOLOGY: We analyzed data on
      404 patients with early gastric cancer invading the submucosa who underwent
      gastrectomy from 1979 to 1998 in the National Kyushu Medical Center, Fukuoka,
      Japan. The postoperative survival rate of patients with standard D2 dissection
      was compared with cases of those with limited D2 dissection which was defined as
      confined as D2 dissection dissections No.7 (lymph nodes were those along the left
      gastric artery), No.8 (lymph nodes along the anterosuperior common hepatic
      artery) and No.9 (lymph nodes along the celiac artery). RESULTS: Of the 404
      patients, 52 and 17 had lymph node metastasis in group 1 and group 2 nodes,
      respectively. Of 17 patients with lymph node metastasis in group 2, 14 (82.4%)
      had metastasis confined to No.7, 8 and 9 of group 2 nodes. The 5-year survival
      rate of patients with submucosal cancer without lymph node metastasis was 94.4%
      after limited D2 dissection and 97.3% after standard D2 dissection, respectively.
      CONCLUSIONS: The appropriate prophylactic lymph node dissection for early gastric
      cancer invading the submucosa without lymph node metastasis was considered to be
      minimized to limited D2 dissection.

PMID- 15143937
TI  - Does the surgical stress associated with palliative resection for patients with
      incurable gastric cancer with distant metastasis shorten their survival?
AB  - BACKGROUND/AIMS: In cases of incurable stage IV gastric cancer with distant
      metastases, surgical treatment has usually consisted merely of palliation. The
      effect of palliative resection in these highly advanced cases remains
      controversial. Palliative resection may be prohibited by the potential
      disadvantages of surgical stress. METHODOLOGY: Over the past 23 years, 382 stage
      IV incurable gastric cancer patients with distant metastases were classified into
      a resection group (group R) whose subjects underwent a palliative resection of
      the primary tumor and the non-resection group (group N) who were treated without
      resection of primary tumor. In order to exclude patients with very poor prognosis
      due to irresectability even if trying to resect, we restricted the subjects to
      patients who survived more than 30 and 60 days and some months and estimated the
      mean survival. Cumulative survival rates were calculated by using the Kaplan
      Meier method, and the mean survivals of groups R and N were compared. RESULTS: A
      significantly longer mean survival was observed in group R than in group N (381
      vs. 181 days, P<0.0001). Restricting the subjects to patients who survived more
      than 30 and 60 days, there is also a significant difference between the mean
      survival of group R and that of group N. However, restricting the subjects to
      patients who survived more than 300 days, no significant difference was seen
      between the two groups. The rate of hospital death was higher in group N than in
      group R (15.9% vs. 3.4%) CONCLUSIONS: Palliative resection of the primary tumor
      in stage IV gastric cancer is meaningful in view of hospital stay, long-term
      survival, and satisfaction with the treatment. We should resect the primary tumor
      in cases in which it is resectable.

PMID- 15143941
TI  - Genes inside the cagPAI of Helicobacter pylori are not associated with gastric
      cancer in Japan.
AB  - BACKGROUND/AIMS: In Japan, infection with cagA-positive H. pylori is not
      associated with gastric cancer unlike Western populations. Both cagE and
      Agrobacterium VirD4 homologue are genes inside the cagPAI. The aim of this study
      was to examine whether the presence of genes inside the cagPAI, cagA, cagE and
      Agrobacterium VirD4 homologue, is associated with gastric cancer in Japan.
      METHODOLOGY: Thirty-nine patients with gastric cancer and 39 subjects with only
      chronic gastritis were infected with H. pylori. Seventy-eight H. pylori strains
      were isolated from gastric biopsies and the presence of 23S rRNA, cagA, cagE, and
      VirD4 homologue were studied by polymerase chain reaction. RESULTS: The
      positivity of cagA was 97.4% in patients with gastric cancer, and 92.3% in
      control subjects. Thirty-six strains (92.3%) isolated from patients and 35
      strains (89.7%) from control subjects had both cagE and VirD4. All the 3 cagA
      negative strains did not have both cagE and VirD4. There were no significant
      differences in the positivities of cagA, cagE, and VirD4 between patients and
      control subjects. CONCLUSIONS: cagE and VirD4 were possessed by most Japanese
      strains, and thus the structure of the cagPAI of H. pylori might not be
      associated with the development of gastric cancer in Japan.

PMID- 15143938
TI  - The effect of Helicobacter pylori infection on apoptosis and cell proliferation
      in gastric epithelium.
AB  - BACKGROUND/AIMS: Helicobacter pylori (Hp) may affect the normal balance between
      gastric epithelial cell proliferation and epithelial cell death, interfering thus
      with the maintenance of gastric mucosa integrity. The aim of this study was to
      investigate the effect of Hp infection on cell proliferation index (PI) and
      apoptotic index (AI) in gastric epithelium of the antrum and corpus. METHODOLOGY:
      Prospective study in forty-one patients with functional dyspepsia (14 males, 27
      females, average age = 54+/-16.1 years). Day one: upper digestive endoscopy with
      biopsies of the antrum and corpus, and a cytological smear of the antral area for
      AgNOR (argyrophilic nucleolar organizer region) analysis. Biopsies for the
      programmed tests were sent in separate labeled containers: to study AI (antibody
      anti-M30), PI (antibody anti-Ki 67) and histology (Sydney criteria and the
      detection of Hp). Detection of the AgNORs through the Gimenez-Mas et al.
      technique, using Visilog-Microptic Software. Day two: a blood sample was drawn
      from each patient for the serologic detection of the status CagA and VacA, and a
      breath test was carried out with 13C-Urea. STATISTICS: SPSS program with the
      application of Student's t, chi-square and Fisher tests. RESULTS: 24 patients
      were Hp(+) and 17 Hp(-). The PI (Ki 67 and AgNORs) in the antral area was
      significantly increased in the Hp(+) patients. AI showed no significant
      difference in the subgroups Hp(+) and Hp(-). Both subgroups showed increased PI
      in the antrum and increased AI in the gastric corpus. There was significantly
      higher PI in CagA(+), without an increase in the AI. The AI was significantly
      higher in CagA(-), when compared with CagA(+). The VacA protein had no influence
      on PI and AI. Acute and chronic gastritis was more frequent and more severe in
      Hp(+) patients. This group lacked any correlation between the histological
      findings and the PI, but the opposite was the case between AI and the degree of
      cellular infiltration. CONCLUSIONS: In patients with functional dyspepsia, Hp
      infection induces an increase of PI, with significant presence in the antrum
      area, without the corresponding increase in AI. Cag A(+) promotes the increase of
      PI, and Cag A(-) promotes the increase of AI. The Vac A status has no influence
      on the PI or AI. The degree of cellular infiltration interferes with AI.

PMID- 15143943
TI  - Correlation of lymph node metastases and expression of matrix metalloproteinase-7
      in patients with gastric cancer.
AB  - BACKGROUND/AIMS: Matrix metalloproteinase-7 (MMP-7) is thought to play an
      important role in the progression of cancer invasion. However, the expression of
      MMP-7 in primary and nodal lesions of gastric cancer is unknown. METHODOLOGY:
      Expression of MMP-7 protein in primary and nodal lesions of human gastric cancer
      was evaluated by immunohistochemistry. Expression of MMP-7 mRNA in the sentinel
      node, i.e. the first lymph node in the lymphatic basin to receive metastases from
      the primary tumor, was evaluated by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: Among primary lesions, 73 (48%) of 153 tumors were
      strongly positive for MMP-7. Strong positivity rates in the primary lesion were
      associated with deep invasion of the gastric wall, nodal metastases, and
      infiltration of vessels or lymphatics. Five-year survival rates were 43.8% in
      patients with strongly positive tumors and 75.0% in patients with weakly positive
      tumors. Among nodal metastases, 53 (76%) of 70 lesions were strongly positive for
      MMP-7, which was significantly higher than the strong positivity rate for primary
      lesions. Strong positivity rates in metastatic lesions were significantly higher
      when metastatic lymph nodes were present in group 2 or more. All of six patients
      with peritoneal dissemination in the absence of gastric serosal invasion had
      nodal metastases strongly positive for MMP-7. Five-year survival rates were 17.5%
      in patients with strongly positive nodal metastases and 68.6% in patients with
      weakly positive nodal metastases. RT-PCR demonstrated MMP-7 expression in
      sentinel nodes of 3 cases of 30. All 3 cases had metastases not only in the
      sentinel node but also in non-sentinel nodes. However, in 27 cases, including 24
      without metastases and 3 with metastases in the sentinel nodes only, expression
      of MMP-7 in the sentinel nodes was not observed. CONCLUSIONS: MMP-7 may
      contribute to the invasion of both primary and nodal lesions in patients with
      gastric cancer. The MMP-7 expression is a useful prognostic factor, and
      evaluating the expression in sentinel node may help surgeons determine what level
      of lymph node dissection should be performed.

PMID- 15143936
TI  - Clinical merit of subdividing gastric cancer according to invasion of the
      muscularis propria.
AB  - BACKGROUND/AIMS: In TNM classification, carcinoma that has invaded the muscularis
      propria (mp) and cancer that has invaded the subserosa are both categorized as T2
      cancer. However, some mp gastric cancer patients have a good postoperative
      course, similar to that of early gastric cancer patients. We performed a
      retrospective analysis of 74 patients with mp gastric cancer, based on the depth
      of mp invasion. METHODOLOGY: The clinicopathologic features of 74 cases of
      gastric cancer invading the mp (but no further) were subdivided according to
      depth of invasion, retrospectively reviewed and compared with surgical features
      of 165 patients with gastric cancer invading the submucosa (sm gastric cancer).
      For each tumor, we evaluated the degree of tumor invasion in the mp layer at a
      magnification of x100, using the section that showed the greatest extent of
      invasion. The patients were classified into 2 groups: mp1, tumor was limited to
      the first of the 3 mp layers; mp2, tumor had expanded beyond the first layer.
      RESULTS: Of the 74 mp gastric cancer patients, 30 were classified as mp1 and 44
      were classified as mp2. Patients with mp1 gastric cancer had significantly more
      macroscopic signs of early gastric cancer, a lower frequency of lymph node
      metastasis, and a higher rate of operative cure than patients with mp2 gastric
      cancer. The incidence of lymph node metastasis among mp1 gastric cancer patients
      was almost equal to that of the 165 sm gastric cancer patients. The 5-year
      survival rate of mp1 patients was significantly better than that of mp2 patients
      (p<0.05), but was similar to that of the 165 sm gastric cancer patients (84%)
      (p<0.05). CONCLUSIONS: There were clear differences in clinical features between
      the mp1 and mp2 gastric cancer patients. Subdivision of mp gastric cancer
      according to depth of invasion may enable more precise prognosis and treatment of
      mp gastric cancer patients. The clinicopathological findings and surgical outcome
      of the mp1 patients were similar to those of the sm gastric cancer patients.
      Thus, mp1 patients may require treatment that is similar to treatment
      administered to patients with early gastric cancer.

PMID- 15143942
TI  - Gastric adenocarcinoma after renal transplantation.
AB  - BACKGROUND/AIMS: Little is known of the characteristics of gastric adenocarcinoma
      after renal transplantation. This study was performed to find out the incidence
      and clinicopathological features of gastric adenocarcinoma after renal
      transplantation in an endemic area for gastric cancer. METHODOLOGY: Between April
      1979 and March 2001, fourteen gastric adenocarcinoma patients (0.7%) out of 2000
      renal transplant recipients in a single institute were retrospectively reviewed.
      RESULTS: Gastric adenocarcinoma was identified in 14 recipients (8 males and 6
      females; mean age 47.6 years) about 60 months after renal transplantation. Four
      patients had early gastric cancer; ten patients had cancer in an advanced stage.
      Eleven patients underwent surgical resection, while three with distant metastasis
      were treated symptomatically. There was no postoperative mortality. Seven
      patients survived without evidence of recurrence, whereas four died of recurrence
      and three of gastric cancer progression. CONCLUSIONS: Renal transplant recipients
      are at increased risk of gastric adenocarcinoma, the most common malignancy in
      Korea. With curative surgery, favorable prognosis can be anticipated when the
      diagnosis is made at an early stage. Regular endoscopic examination for early
      diagnosis is recommended during the follow-up period after renal transplantation
      in a gastric cancer endemic area.

PMID- 15143939
TI  - Postoperative clinical evaluation following pylorus-preserving gastrectomy.
AB  - BACKGROUND/AIMS: Recent pathological study demonstrated that extended
      lymphadenectomy is not always necessary for patients with early gastric cancer.
      METHODOLOGY: Twenty-eight patients underwent pylorus-preserving gastrectomy. The
      clinicopathological findings of patients with pylorus-preserving gastrectomy were
      compared to those of 58 patients with conventional distal gastrectomy. RESULTS:
      There were no significant differences in surgical duration, blood loss, blood
      chemistry, food intake, and body weight loss. Regarding abdominal symptoms, early
      dumping syndrome was significantly higher in distal gastrectomy than in pylorus
      preserving gastrectomy (35.6% vs. 12.0%, p<0.05). Remnant gastritis was also
      significantly higher in distal gastrectomy (57.1% vs. 27.7%, p<0.05). However,
      food residue tended to be more frequently seen in pylorus-preserving gastrectomy
      (33.3% vs. 61.1%, p=0.052). Based on questionnaire results, the rate of patient
      satisfaction with their surgical outcome tended to be lower in pylorus-preserving
      gastrectomy than in distal gastrectomy (84.0% vs. 95.6%, p=0.098). The tendency
      was more pronounced in patients over 70 years old (77.8% vs. 100%, p=0.065).
      CONCLUSIONS: Pylorus-preserving gastrectomy is superior to conventional distal
      gastrectomy in the prevention of dumping syndrome and reflux gastritis. However,
      since delayed emptying is frequently seen post pylorus-preserving gastrectomy,
      this procedure is not recommended for older patients under simplistic
      indications.

PMID- 15143944
TI  - Effect of the anastomosis-site after Billroth I gastrectomy on the motility of
      the remnant stomach.
AB  - BACKGROUND/AIMS: Gastric emptying, in healthy individuals, is a highly regulated
      process, and plasma cholecystokinin plays a major role in its feedback
      regulation. However, the hormonal regulation of postprandial gastric emptying of
      the remnant stomach after distal gastrectomy with Billroth I reconstruction
      procedure has not been well described. The aim of this study is to characterize
      the gastroduodenal motility and gastric emptying of the two anastomosis-methods
      after Billroth I gastrectomy, while assessing the effect of cholecystokinin on
      the motility of the remnant stomach. METHODOLOGY: Two types of anastomosis (end
      to-end, side (posterior wall)-to-end) after Billroth I gastrectomy were measured
      with strain gauge force transducers, and evaluated as to gastroduodenal motility,
      gastric emptying, gastrointestinal hormones (cholecystokinin, gastrin), and blood
      glucose associated with food administration. RESULTS: Remnant stomachs with side
      to-end anastomosis showed superior motility as compared to those with end-to-end
      anastomosis. Plasma cholecystokinin was higher in the end-to-end anastomosis
      group. No differences as to gastric emptying, levels of plasma gastrin, or blood
      glucose were observed between the two groups. CONCLUSIONS: Plasma cholecystokinin
      may explain the difference in motility index between the two groups.

PMID- 15143947
TI  - Successfully treated metachronous liver metastasis of alpha-fetoprotein-producing
      early gastric cancer: case report.
AB  - We treated a 57-year-old male with liver metastasis derived from an alpha
      fetoprotein-producing early gastric cancer. Eleven months after distal
      gastrectomy with D2 lymph node dissection, the patient underwent hepatectomy of
      segment 4 to resect a liver tumor 3 cm in diameter found by abdominal computed
      tomography. Immunohistochemical examination of the stomach and liver specimens,
      using anti-alpha-fetoprotein antibody, showed partial alpha-fetoprotein
      expression in both the primary gastric and metastatic hepatic tumors. The
      patient's serum alpha-fetoprotein level had been elevated at 302 ng/mL before
      hepatectomy, but the level remained below 5 ng/mL postoperatively. The patient
      remains alive without tumor recurrence 3 years after hepatectomy. There have been
      few previous reports of good outcome after curative resection of a metachronous
      liver metastasis derived from alpha-fetoprotein-producing gastric cancer. The
      assessment of serum alpha-fetoprotein level may be useful for detecting and
      monitoring liver metastasis in gastric cancer, especially for alpha-fetoprotein
      producing tumors.

PMID- 15143946
TI  - Complication of jejunal pouch interposition after proximal gastrectomy: case
      report.
AB  - Interposition of a jejunal pouch after proximal gastrectomy is a popular
      reconstruction method in Japan, because it produces a good quality of life soon
      after surgery. Many reports have described its usefulness. However, there are few
      reports describing its complications. We report here for the first time a case of
      pouch stasis needing surgery. A 23-year-old man underwent proximal gastrectomy
      with interposed jejunal pouch for traumatic strangulated diaphragmatic hernia.
      Three years later, he complained of persistent vomiting. Since surgery, he had
      eaten as much as other young people. An upper gastrointestinal series showed
      dilatation of the jejunal pouch and stasis of contrast medium. Since conservative
      therapy was not effective, surgery was performed. In the operative findings, the
      jejunal pouch was extremely dilated, the remaining stomach had become atrophic,
      and moreover, the anastomosis was severely distorted. It was considered that
      frequent excessive ingestion caused irreversible dilatation of the jejunal pouch,
      resulting in pouch stasis. Even though the jejunal pouch is interposed for
      reconstruction, it is very important to give nutritional guidance to patients,
      especially young patients, to prevent pouch stasis caused by excessive food
      ingestion.

PMID- 15143945
TI  - Effect of human noxa on irinotecan-induced apoptosis in human gastric carcinoma
      cell lines.
AB  - BACKGROUND/AIMS: A protein BH3-only member bcl-2 family, Noxa is a proapoptotic
      mediator for p53-induced apoptosis. We analyzed the effect of Noxa on p53-induced
      apoptotic gastric carcinoma cell lines. METHODOLOGY: The expressions of human
      Noxa (hNoxa) mRNA on human gastric carcinoma cell lines were assessed with RT
      PCR. Further, hNoxa antisense and sense S-oligodeoxynucleotide (ODN) were used to
      analyze the effect of hNoxa on p53-induced apoptotic gastric carcinoma cell
      lines. RESULTS: Various levels of hNoxa mRNA expression were detected in all
      gastric cell lines. MKN45 that has wild-type p53 showed severe inhibition by
      irinotecan compared with MKN28, which has mutated p53. Cell growth under hNoxa
      antisense S-ODN treatment did not differ from that under sense S-ODN treatment in
      MKN28. On the other hand, the suppression of cell growth in MKN45 decreased with
      hNoxa antisense S-ODN treatment as compared to hNoxa sense S-ODN treatment. MKN45
      cells exhibited DNA fragmentation clearly after 24 hr of 3 mM hNoxa sense S-ODN
      treatment. The DNA fragmentation in MKN45 was inhibited by hNoxa antisense S-ODN
      treatment. CONCLUSIONS: It seems that hNoxa plays an important role in induction
      of apoptosis on p53 wild type gastric carcinoma cell lines.

PMID- 15143949
TI  - [Management of stroke in a ward of internal medicine. Limits and prospects].
AB  - Precocious admission to specifically "dedicated" wards proved to improve
      reduction of mortality and degree of residual disability in patients with stroke,
      even if their inhomogeneous distribution gets most patients admitted to wards of
      Internal Medicine. We purposed to evaluate the importance of this problem, to
      check adhesion to the national guidelines and to show the main problems in
      management of patients with stroke in the Operative Unit of Internal Medicine,
      Vascular and Metabolic Diseases of the IRCCS S. Matteo Hospital of Pavia. 143
      patients with stroke were admitted in 2001, 126 were ischemic, 17 hemorragic; the
      mean age was of 73. The most frequent risk factors were hypertension, diabetes,
      smoke and atrial fibrillation. 59% of patients were admitted within 6 hours from
      onset of symptoms. Within the ischemic subtypes, 17.5% were atherotrombothic,
      16.7% cardioembolic, 23.8% lacunar and 42% with undetermined etiology. Lacunar
      syndromes were the most part. 80% of patients underwent computed tomography, 50%
      underwent epiaortic Doppler sonography, 38% echocardiography. 61% of ischemic
      subtypes underwent acute antiplatelet treatment. Complications were prevalent in
      oldest patients. Mortality of inpatients was 17%, influenced by age,
      hypertension, severe sensorial compromission at admission, cardioembolism and
      complications. This study proved leak of adhesion to national guidelines which
      brought to inadequate accuracy in diagnosis and difficulty in making correct and
      coherent therapeutic choices. At least in great hospitals, "dedicated" areas in
      wards of Internal Medicine with selected, trained and motivated staff should be
      desirable.

PMID- 15143950
TI  - [Chronic idiopathic neutropenia. A cytofluorimetric method to detect
      antineutrophil antibodies].
AB  - A cytofluorimetric method to detect antineutrophil antibodies was carried out in
      sixty adults suffering from chronic idiopathic neutropenia (5 patients with
      severe neutropenia, 16 with moderate neutropenia, 39 with mild neutropenia). Both
      the direct and the indirect tests were carried out using F(ab')2 goat anti-human
      FITC-conjugates immunoglobulins on whole blood samples. Fifteen patients (25%)
      were found to have antineutrophil antibodies both on the neutrophil surface and
      in serum. Most positive patients were suffering from severe neutropenia (4
      patients) and moderate neutropenia (8 patients). Only four positive patients were
      suffering from infections.

PMID- 15143948
TI  - [Clinical use of erythropoietin].
AB  - The introduction of recombinant human erythropoietin (RHuEPO) has dramatically
      changed the therapeutic approach to the anemia of chronic renal failure. Clinical
      studies have also demonstrated that RHuEPO is effectiveness in various non-uremic
      conditions, such as anemia associated with onco-hematological disorders,
      prematurity, HIV infection and to reduce the exposure to allogeneic blood in
      surgical patients. In this review, we briefly analyze the main clinical
      applications of RHuEPO, with particular attention to the potential complications
      deriving from its use.

PMID- 15143951
TI  - [Pyogenic sacroiliitis complicated by iliopsoas muscle abscess].
AB  - Both pyogenic sacroiliitis and iliopsoas muscle abscess are uncommon infectious
      entities, and their coexinstence has been reported in very few patients. We
      present here the case of a woman who developed a large iliopsoas abscess as a
      consequence of a pyogenic sacroiliitis, initially misdiagnosed as a common
      sciatica and treated with corticosteroids. The patient was cured by the surgical
      drainage of the abscess and a long-lasting antibiotic treatment. We discuss
      diagnostic difficulties linked to the two infectious entities, their possible
      pathogenic connections, the role of imaging procedures, and therapeutic options.
      We conclude that pyogenic sacroiliitis and the potential evolution to an
      iliopsoas abscess must be taken into consideration in the differential diagnosis
      of lower back pain, especially if fever is a concomitant sign.

PMID- 15143952
TI  - [Inflammation and atherosclerosis].
AB  - The link between atherosclerosis with phlogosis is well knowed by a long time: in
      this article the correlations among lipoproteins, acute inflammation's proteins,
      innate immunity, but also nexus with infections and reactive oxygene species of
      scavenger receptors called Toll-like and antiinflammatory statines's property are
      also reviewed.

PMID- 15143954
TI  - [Adrenomedullin in cardiovascular pathology].
AB  - Adrenomedullin (AM), inducing a potent and powerful hypotensive activity caused
      by dilatation of resistance vessels, has elicited interest for its cardiovascular
      actions. AM is secreted from various cell type, including vascular endothelial
      and smooth muscle cell. AM plasma levels are increased in various cardiovascular
      diseases as heart failure and hypertension and may be involved in
      pathophysiological changes in cardiovascular diseases.

PMID- 15143953
TI  - [Inflammation, hyperresponsiveness and reversible bronchial obstruction in
      asthma: are they related?].
AB  - Inflammation, hyperresponsiveness and reversible bronchial obstruction are three
      features of asthma. Even if numerous studies have in part clarified the
      relationships between them, some pathogenetic aspects nevertheless remain unclear
      even today. The origins of hyperresponsiveness still escape us and the
      relationship of this with the entity of bronchial inflammation looks weak.
      Bronchial obstruction does not result correlated with the symptoms of asthma or
      with hyperresponsiveness. In some studies there has been reported a significant
      relationship between degree of hyperresponsiveness and reversibility after
      inhalation of beta2-agonists. Given the scarce interdependence highlighted by
      these features of asthma, it is presently an argument for discussion whether the
      valuation of each is useful during the monitoring of the state and evolution of
      the disease.

PMID- 15143955
TI  - [New insights in the pathogenesis of prothrombotic state associated with
      hypercholesterolemia].
AB  - Hypercholesterolemia and overt atherosclerotic disorders have been associated
      with a low-grade inflammation that involves not only the intrinsic cells of the
      artery wall, but also circulating cells. Platelets as well as monocytes
      participate importantly in this disease process through the release of a wide
      variety of biologically active substances. Recent findings on the inflammatory
      actions of platelets have opened new perspectives in the comprehension of the
      pathogenetic mechanism(s) of atherosclerosis. Stimulated platelets, in fact,
      actively synthesize proinflammatory cytokines which have been all involved in the
      inflammatory process associated to hypercholesterolemia and plaque development.
      In this context, increasing evidence suggests that interrelated inhibition of
      inflammation and thrombosis induced by statins could largely contribute to
      clinical benefits from lipid-lowering therapy.

PMID- 15143956
TI  - Belgian consensus on recommendations for standards of care for women with
      epilepsy before, during and after pregnancy.
AB  - Women with epilepsy (WWE) have an increased risk of complications during
      pregnancy, which however can be minimized by optimal, interdisciplinary patient
      management. The aim of any therapy is to achieve an optimal balance between
      avoidance of seizures, which may be harmful to both mother and foetus, and
      minimization of foetal and neonatal exposure to deleterious influences of
      antiepileptic drugs. Suitable measures include early and regular counselling of
      the young WWE about contraception and planning of pregnancy, optimisation of drug
      treatment (choice of the right drug and dosage also in view of altered
      pharmacokinetics, avoidance of polytherapy, therapeutic drug monitoring etc.), in
      time folate substitution, and close follow-up of the patient during and after
      pregnancy. Until now, many issues such as underlying factors of malformations
      have not been clearly elucidated. Nonetheless, chances for an unproblematic
      pregnancy of WWE are high.

PMID- 15143957
TI  - Lipids in ischemic stroke subtypes.
AB  - In secondary prevention, reduction of the risk of recurrent ischemic stroke might
      be expected with statins if a correlation can be established between
      hyperlipidemia and ischemic stroke or some specific ischemic stroke/TIA subtypes.
      However, such correlation remains controversial, and more particularly with the
      etiologic stroke/TIA subtypes. Few studies have evaluated the plasma lipid
      profile in different ischemic stroke subtypes, and notably in lacunar infarctions
      and cardioembolic strokes. The objectives of this case-control study was to
      determine (1) which cholesterol fractions is associated with large vessel disease
      (LVD), small vessel disease (SVD), and cardioembolic disease (CED); (2) whether
      hypertriglyceridemia is related more to any particular stroke subtype; and (3)
      whether the lipid profile is different between LVD and SVD which are both
      responsible for atherothrombotic cerebral ischemia. From a cohort of 485
      patients, were selected 240 consecutive cases with ischemic stroke (n = 182) or
      transient ischemic attack (n = 58) due to a single etiology. The levels of total
      cholesterol (total-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and
      triglycerides (TG) were measured in 61 patients with LVD, in 65 with SVD, and in
      114 with CED, and compared with age- and sex-matched control subjects. Additional
      analysis was performed to compare the lipid profile between LVD and SVD after
      adjustment for other risk factors. Compared to controls, the total-C level was
      significantly higher in patients with SVD (p = 0.005) and LVD (p = 0.018). A
      significant increase in the LDL-C level (p < 0.004) and a significant decrease in
      the HDL-C level (p = 0.001) were only observed in the LVD patients. The three
      stroke subtypes showed higher TG levels than the controls (CED, p = 0.037; SVD, p
      < 0.001; LVD, p = 0.014). The plasma lipid profile was similar in the SVD and LVD
      subtypes except for HDL-C, which was significantly lower in LVD than in SVD (p =
      0.047). Logistic regression adjusted for confounders showed that decreased HDL-C
      (p = 0.020), and smoking (p = 0.019) were significant discriminative factors for
      LVD vs. SVD. In conclusion, this controlled study shows that hypertriglyceridemia
      is commonly found in patients with ischemic cerebrovascular disease whatever the
      etiologic subtype, whereas hypercholesterolemia is related more to SVD and LVD.
      In addition to hypertension and diabetes, hypercholesterolemia may also be
      involved in the etiology of SVD and differs from LVD by a lower decrease in HDL
      C.

PMID- 15143958
TI  - The effects of phenytoin and phenobarbital on seizures induced by
      imipenem/cilastatin in rats.
AB  - The effects of phenytoin (PHT) and phenobarbital (PHB) on EEG activity and
      behavior was studied in the model of epilepsy induced by intracerebroventricular
      (i.c.v.) administration of imipenem/cilastatin (Imi/Cil). Under intraperitoneal
      (i.p.) sodium pentobarbital anesthesia adult male Wistar albino rats were
      implanted with electrodes and cannulas were placed into the right lateral
      ventricle. Animals were divided into groups: 1) Imi/Cil (100/100 microg, i.c.v.),
      2) PHT (40 mg/kg) + Imi/Cil (100/100 microg, i.c.v), 3) PHT (80 mg/kg) + Imi/Cil
      (100/100 microg, i.c.v.), 4) PHT (160 mg/kg) + Imi/Cil (100/100 microg, i.c.v.),
      5) PHB (50 mg/kg) + Imi/Cil (100/100 microg, i.c.v.), and 6) PHB (80 mg/kg) +
      Imi/Cil (100/100 microg, i.c.v.). PHT and PHB were injected intraperitoneally
      (i.p.) 1 h before Imi/Cil. Seizures were scored according to the scale: 0--normal
      behavior; 1--twitching, 2--head nodding, forelimb clonus, 3--rearing, and 4-
      clonic-tonic convulsions. Imi/Cil provoked maximal seizures in all animals, and
      all rats died 10 - 18 min after the injection. Epileptiform activity preceded
      behavioral seizures. Clonic-tonic seizures were associated with continuous bursts
      of high-frequency high-amplitude spikes in the EEG. PHT and PHB suppressed
      Imi/Cil-induced seizures dose-dependently. PHB reduced epileptiform discharges
      during behavioral seizures elicited by Imi/Cil, while PHT had no effect on EEG
      epileptic phenomena. These results suggest that PHT acts as anticonvulsant, and
      PHB as anticonvulsant and antiepileptic agent in the model of epilepsy induced by
      Imi/Cil.

PMID- 15143959
TI  - Diagnostic and therapeutic impact of ambulatory electrocardiography in acute
      stroke.
AB  - Detection of paroxysmal atrial fibrillation (PAF) in patients with recent
      ischemic stroke or TIA suggests a cardioembolic etiology and leads to initiation
      of oral anticoagulation in suitable candidates. We assessed the diagnostic and
      therapeutic impact of adding ambulatory electrocardiography (24 hr ECG) to a
      standardised ischemic stroke workup. METHODS: We measured the frequency of
      detection of PAF in consecutive stroke patients who underwent 24 hr ECG that was
      not diagnosed clinically or on a standard 12-lead ECG. RESULTS: One hundred forty
      five ischemic stroke patients were included. 24 hr ECG was obtained in 136
      patients (93.8%). Clinically unsuspected PAF was detected on 24 hr ECG in 7
      patients (5.1%). The secondary prevention measure changed from antiplatelet
      agents to oral anticoagulation in 6 of 7 patients. CONCLUSION: Our findings
      suggest that ambulatory electrocardiography is a valuable diagnostic tool in the
      workup of stroke patients. Further prospective studies are needed to identify,
      subtypes of patients in whom the yield of ambulatory electrocardiography is
      higher.

PMID- 15143960
TI  - Deep brain stimulation in movement disorders. The applications reconsidered.
AB  - In this study the role of DBS in advanced Parkinson disease (PD) is re-evaluated
      and new indications in the field of movement disorders are explored. The authors
      performed unilateral pallidal stimulation in 26 patients with advanced PD. At
      long-term follow-up review, the motor effect is unsatisfying. The authors
      conclude that unilateral pallidal stimulation is not a favourable treatment
      option for patients with advanced PD. Bilateral subthalamic nucleus stimulation
      was performed in twenty patients with advanced PD. After a minimum follow-up of 4
      years, there was still a significant improvement in motor function and functional
      performance in all patients. One side-effect of the stimulation was however
      rather concerning: four patients presented with stimulation-induced hypomanic to
      manic characteristics. Bilateral subthalamic stimulation was performed in four
      patients with multiple system atrophy-parkinsonism. At long-term follow-up, the
      patients fared better with than without stimulation. The authors finally present
      a completely new indication for DBS: Tourette syndrome (TS). They review the
      literature on surgical procedures performed in TS, all of which consisted of
      making lesions. Three TS patients are presented on which bilateral thalamic
      stimulation was performed. At long-term follow-up, all major tics had
      disappeared, as well as associated behavioral disturbances.

PMID- 15143961
TI  - Hypnic headache: a case report with polysomnography.
AB  - We report on a case of nocturnal headache attacks fulfilling the criteria for
      hypnic headache syndrome. Using an overnight polysomnography, one nocturnal
      headache attack was captured during the REM phase of sleep. Quality of sleep was
      poor with desaturation episodes. However, the hypnic headache attack was not
      associated with oxygen desaturation. This additional case supports the view of a
      relationship between the hypnic headache syndrome and the REM sleep stage.
      Lithium therapy decreased the intensity and frequency of headache attacks.

PMID- 15143962
TI  - Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and
      angiogenesis.
AB  - AIMS AND BACKGROUND: The PI3 kinase signalling pathway is now accepted as being
      at least as important as the ras-MAP kinase pathway in cell survival and
      proliferation, and hence its potential role in cancer is of great interest. The
      purpose of this review is briefly to examine evidence for an involvement of PI3K
      in human cancers, discuss the mechanisms by which its activation promotes tumor
      progression, and consider its utility as a novel target for anticancer therapy.
      METHODS AND STUDY DESIGN: A Medline review of recent literature concerning the
      role of PI3 kinase in tumor progression--mechanisms of action and clinical
      implications. RESULTS: Evidence is presented that misregulation of the PI3 kinase
      pathway is a feature of many common cancers, either by loss of the suppressor
      protein PTEN, or by constitutive activation of PI3 kinase isoforms or downstream
      elements such as AKT and mTOR. This activation potentiates not only cell survival
      and proliferation, but also cytoskeletal deformability and motility; key elements
      in tumor invasion. In addition the PI3K pathway is implicated in many aspects of
      angiogenesis, including upregulation of angiogenic cytokines due to tumor hypoxia
      or oncogene activation and endothelial cell responses to them. These cytokines
      signal though receptors such as VEGF-R, FGF-R and Tie-2 and potentiate processes
      essential for neoangiogenesis including cell proliferation, migration,
      differentiation into tubules and "invasion" of these capillary sprouts into
      extracellular matrix (ECM). CONCLUSIONS: A more complete understanding of the
      role of the PI3 kinase pathway in cancer will lead the way to the development of
      more potent and selective inhibitors which should be a useful adjunct to
      conventional therapies, potentially interfering with tumor progression at several
      pivotal points; in particular cell survival, invasion and angiogenesis.

PMID- 15143963
TI  - Case-control study of anaplastic thyroid cancer.
AB  - AIMS AND BACKGROUND: The aim of the present study was to test some hypothetical
      risk factors for anaplastic thyroid cancer. STUDY DESIGN: A case-control study
      comprised 110 patients with histologically or cytologically verified anaplastic
      thyroid cancer and 110 hospital controls individually matched with cases by sex,
      age, place of residence and time of hospitalization. Univariate and multivariate
      logistic regressions were used for data analysis. RESULTS: According to the
      conditional logistic regression analysis, the following factors were
      significantly and independently related to anaplastic thyroid cancer: history of
      goiter or thyroid nodules (odds ratio, OR, 37.55; 95% confidence interval, CI,
      4.86-290.11), history of residence in endemic goiter area (OR, 2.56; 95% CI, 1.05
      6.22), history of previous malignant non-thyroid tumor (OR, 5.51; 95% CI, 1.04
      29.25), diabetes mellitus (OR, 4.06; 95% CI, 1.29-12.81) and low educational
      level (OR, 2.44; 95% CI, 1.17-5.06). CONCLUSIONS: The results are in line with
      the current knowledge on factors related to thyroid cancer, except for the
      association between thyroid cancer and diabetes mellitus, which as far as we know
      has not yet been reported.

PMID- 15143964
TI  - Intraoperative radiotherapy during breast conserving surgery in patients
      previously treated with radiotherapy for Hodgkin's disease.
AB  - AIMS AND BACKGROUND: Women who have received radiotherapy for Hodgkin's disease
      have an increased risk of developing breast cancer. Breast-conserving surgery
      followed by breast irradiation is generally considered to be contraindicated in
      such patients owing to the high cumulative radiation dose to the breast.
      Mastectomy is therefore recommended as the preferred treatment option in these
      women. METHODS: We report 3 patients affected by breast cancer who had previously
      been treated with mantle radiation for Hodgkin's disease and on whom breast
      conserving surgery and full-dose intraoperative radiotherapy with electrons
      (ELIOT) were performed. RESULTS: A total dose of 17 Gy (prescribed at 100%
      isodose) in one case and 21 Gy (at the 90% isodose) in two cases was delivered
      directly to the mammary gland without acute complications and with good cosmetic
      results. CONCLUSIONS: In women previously irradiated for Hodgkin's disease, ELIOT
      could avoid repeat irradiation of the whole breast, thereby permitting
      conservative surgical treatment.

PMID- 15143966
TI  - Percutaneous kyphoplasty: indications and technique in the treatment of vertebral
      fractures from myeloma.
AB  - AIMS AND BACKGROUND: The purpose of our research was to assess the effectiveness
      and safety of percutaneous kyphoplasty, the new method of treatment for pain
      deriving from vertebral compression fractures due to myeloma. METHODS: We treated
      3 patients with pain refractory to conventional medical therapy (analgesics, bed
      rest, bracing with orthopedic devices for more than 4 weeks), localized in the
      lumbar area, painful to the touch and in the absence of neurological signs.
      RESULTS: The method demonstrated a swift pain relief associated with an evident
      augmentation in the resistance and restoration of the vertebral body's
      physiological shape. Polymethylmethacrylate leaks were not observed in the
      epidural or foraminal area, nor were complications such as pulmonary embolism for
      involvement of the venous plexus or related to phenomenon of infections due to
      the procedure, or toxicity due to the polymethylmethacrylate. CONCLUSIONS:
      Kyphoplasty was found to be an effective alternative, simple and safe in the
      treatment of vertebral collapse consequent to multiple myeloma. The same
      injection of polymethylmethacrylate can be done before the radiotherapy
      treatment, thereby synergizing its delayed analgesic action to pain, or after the
      failure or in the case of local recurrence.

PMID- 15143965
TI  - Conservative treatment in noninvasive breast cancer.
AB  - BACKGROUND: The elective treatment for noninvasive breast carcinoma has not yet
      been established. As a result of mammographic screening programs, the incidence
      of noninvasive tumors has increased and has lead to the same controversy already
      present had with invasive carcinomas: mastectomy or conserving therapy. METHODS:
      Since 1990, 101 patients with noninvasive breast cancer were treated with
      irradiation following breast-conserving surgery. All the patients had irradiation
      of the whole breast (mean dose, 47.6 +/- 1.2 Gy). The radiation dose boost to the
      tumor bed was delivered in 28.7% of the cases (mean dose, 21.03 +/- 3.06 Gy), and
      in 71.3%, the boost was not administered. RESULTS: With a median follow-up of 34
      months, survival is 100%. The disease-free survival at 5 years by the Kaplan
      Meier method is 93.6 +/- 8.65. CONCLUSIONS: The conserving treatment is a valid
      option for treatment of patients with ductal carcinoma in situ.

PMID- 15143967
TI  - Outcome of surgical treatment of carcinoma of the pancreas.
AB  - AIMS AND BACKGROUND: Pancreatic resections for neoplastic diseases have a high
      risk of severe intra- and postoperative complications and are associated with
      high mortality rates. They should be performed as a rule in centers specializing
      in this type of surgery. However, it is becoming increasingly likely that such
      tumors may have to be treated in surgery units which are not specifically
      dedicated to pancreatic surgery. The aim of this study was to assess the
      improvements in clinical results in a non-specialized general surgery setting in
      the light of the most recent progress in surgical techniques, drug treatments and
      nutritional support. METHODS AND STUDY DESIGN: We analyzed 48 patients with
      pancreatic cancer treated in our institution over the period from 1980 to 1998:
      36 had cancer of the head of the pancreas, 5 of the ampulla, 1 in the second
      duodenal portion, and 6 of the body-tail. The operations performed consisted of
      13 Whipple pancreaticoduodenectomies with cutting and stapling of the distal
      pancreatic stump at the level of the isthmus, 4 left pancreasectomies, 2 local
      resections of the ampulla, 21 palliative operations, and 2 exploratory
      laparotomies. RESULTS AND CONCLUSIONS: The patients were submitted to follow-up
      including clinical examinations, blood-chemistry tests, and instrumental
      investigations. The mean survival was 18 months in the cases where radical
      surgery was performed, compared to 11 months after palliative surgery. We
      conclude that an improved prognosis can obtain after pancreatic resection. This
      is attributable to a more accurate preoperative staging and to the aid of the
      various forms of nutritional support and pharmacological prophylaxis currently
      available.

PMID- 15143968
TI  - Early results after radiofrequency-assisted liver resection.
AB  - AIMS AND BACKGROUND: Intraoperative blood loss during liver resection remains a
      major concern due to its association with higher postoperative complications and
      shorter long-term survival. The aim of this study was to assess the feasibility
      and safety of a novel concept for liver resection using a radiofrequency energy
      assisted technique. METHODS: From January 2001 to July 2002, 42 patients were
      operated on using radiofrequency energy-assisted liver resection. Radiofrequency
      energy was applied along the resection edge to create a 'zone of desiccation'
      prior to resection with a scalpel. RESULTS: Median resection time was 50 mins
      (range, 30-110). The median blood loss during resection was 30 mL (range, 15
      992). Mean preoperative and postoperative hemoglobin values were 13.7 g/dL (SD +/
      1.6) and 11.8 g/dL (SD +/- 1.4), respectively. No blood transfusion was
      registered, nor was any mortality observed. There were 3 postoperative
      complications, one subphrenic abscess, one chest infection and one biliary leak
      from a hepatico-jejunostomy. Median postoperative stay was 8 days (range, 5-86).
      CONCLUSIONS: Liver resection assisted by radiofrequency energy is feasible, easy
      and safe. This novel technique offers a new method for 'transfusion-free'
      resection without the need for sutures, ties, staples, tissue glue or admission
      to an intensive care unit.

PMID- 15143969
TI  - Paclitaxel administered weekly in patients with docetaxel-resistant metastatic
      breast cancer: a single-center study.
AB  - AIMS AND BACKGROUND: We evaluated retrospectively the efficacy and toxicity of
      paclitaxel in patients with docetaxel-resistant metastatic breast cancer. STUDY
      DESIGN: Paclitaxel (80 mg/m2) was administered weekly to 44 patients who had
      previously received chemotherapy regimens for metastatic breast cancer. All
      patients had progressive disease in spite of having received docetaxel therapy.
      RESULTS: Treatment was repeated until there was evidence of disease progression.
      Objective responses were obtained in 14 of 44 assessable patients (31.8%; 95%
      confidence interval, 17.5-46.1). Fourteen patients had partial responses; none
      responded completely. Seven of 14 responders had primary resistance to docetaxel
      therapy. The median duration of response was 6.1 months (range, 2.1-12.7). The
      median time to progression was 5.0 months. Clinically severe adverse events
      (grade 3 or 4) included neutropenia (27.2%), leukopenia (25.0%), neuropathy
      sensory (13.6%), febrile neutropenia (6.8%), anemia (2.2%), constipation (2.2%),
      and edema (2.2%). Treatment was generally well tolerated and could be continued
      on an out-patient basis. CONCLUSIONS: Weekly paclitaxel is effective in patients
      with docetaxel-resistant metastatic breast cancer. This observation suggests
      partial cross-resistance between paclitaxel and docetaxel. There was no evidence
      for additive cumulative toxic effects of the two taxanes.

PMID- 15143970
TI  - Efficacy and safety of trastuzumab as a single agent in heavily pretreated
      patients with HER-2/neu-overexpressing metastatic breast cancer.
AB  - AIMS AND BACKGROUND: The human epidermal growth factor receptor 2 (HER2) protein
      is a unique and useful target for antibody therapy against breast cancers that
      overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal
      antibody, trastuzumab, was approved for clinical use in the United States in
      1998. It became available in Japan in June 2001. This study focuses on the
      efficacy and safety of trastuzumab as a single agent in second-third line
      treatment of HER2/neu-overexpressing metastatic breast cancer. STUDY DESIGN:
      Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a
      single agent or in combination chemotherapy, for second-third line treatment of
      HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were
      treated with trastuzumab as a single agent. We reviewed retrospectively the
      efficacy and safety of the drug given as a single agent. The expression of HER2
      was determined by immunohistochemical staining. All patients received a standard
      loading dose of 4 mg/kg followed by 2 mg/kg weekly. RESULTS: Patients received a
      median of 16.7 weekly infusions (range, 1-66 infusions). Trastuzumab therapy was
      generally well tolerated. Clinically severe adverse events (grade 3 or 4)
      included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included
      fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as
      were serious hematologic complications. Cardiotoxicity did not occur in the
      study. Three patients had a complete and 3 a partial response, 3 had no change,
      17 had progressive disease, and one was not evaluated. The overall response rate
      in the 26 patients with available data was 23.1% (95% confidence interval, 5.7
      40.4). The median duration of response was 6.4 months (range, 2.5-14.0). The
      median time to progression was 3.1 months (range, 0.2-16.7). Response rates
      differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver
      0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2). CONCLUSIONS:
      Molecular target therapy with trastuzumab appears safe and is generally well
      tolerated. For treatment of metastatic breast cancer, single agent therapy
      produces a durable response in some patients but lacks sufficient efficacy.
      Single agent use of trastuzumab is a viable option for treatment in cases with
      non-life-threatening disease without visceral metastasis.

PMID- 15143971
TI  - Pharmacoeconomic comparison between chronochemotherapy and FOLFOX regimen in the
      treatment of patients with metastatic colorectal cancer: a cost-minimization
      study.
AB  - AIMS AND BACKGROUND: The addition of oxaliplatin to the widely employed De
      Gramont schedule (FOLFOX regimen) in patients with metastatic colorectal cancer
      improved their outcome with a moderate toxicity pattern. The adaptation of the
      delivery rate of 5-fluorouracil, leucovorin and oxaliplatin to circadian rhythms
      (chronotherapy) resulted in a very high drug tolerability with clinical results
      at least comparable to those achieved with the FOLFOX regimen. However,
      chronomodulated infusion seemed to be more expensive, requiring dedicated
      electronic pumps and several disposable materials. The present study aimed to
      compare the direct costs of the two regimens and to determine whether
      chronotherapy was effectively more expensive than the FOLFOX regimen. STUDY
      DESIGN: The direct costs of drug delivery devices derived from various publicly
      available sources and of toxicity management as extrapolated from two published
      studies considering comparable patient subsets were added and compared. RESULTS:
      Pump, central venous system and disposable materials for a single chronotherapy
      cycle were Euro 193 or Euro 212 according to whether the pumps were bought or
      rented, compared to Euro 58 for the FOLFOX regimen. Toxicity management costs
      were Euro 144 vs Euro 288 for the two schemes, respectively. Globally, a single
      course of chronotherapy cost Euro 337 or Euro 356, whereas a single FOLFOX cycle
      cost Euro 346. CONCLUSIONS: Direct costs for a single chronotherapy cycle
      appeared to be comparable to a single course of the FOLFOX regimen. In fact, the
      major material cost of chronochemotherapy devices was balanced by a better
      tolerability profile. The overall improvement in quality of life with
      chronochemotherapy affecting indirect costs, such as reduction of work, and
      intangible costs is worthy of further pharmacoeconomic attention.

PMID- 15143972
TI  - Weekly docetaxel as second-line therapy in non-small cell lung cancer: a phase II
      study.
AB  - INTRODUCTION: Single-agent docetaxel is active as second-line chemotherapy in non
      small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have
      shown response rates of about 20% and 9 months of median survival. Two phase III
      studies documented a survival benefit at 1 year compared to BSC and vinorelbine
      or ifosfamide. Recent trials indicate acceptable activity and a good safety
      profile of weekly docetaxel with doses of 25-43 mg/m2. The aim of our study was
      to confirm this evidence and to evaluate activity and toxicity of weekly
      docetaxel at the dose of 40 mg/m2. PATIENTS ATND METHODS: Twenty-one patients
      with NSCLC entered the study (7 stage IIIB and 14 stage IV): 13 males and 8
      females. Median age was 66 years (range, 53-75). ECOG was O in 6, 1 in 9 and 2 in
      6 patients. All patients were pretreated with a first-line chemotherapy (13
      patients progressed soon after the first line); 6 of them received palliative
      radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2
      in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87
      administrations was delivered (median, 4; range, 1-12). RESPONSES: All patients
      were assessable for response (according to the "intent-to-treat principle") and
      for toxicity. No complete or partial remission was observed; 2 minor responses
      (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented.
      Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to
      early death (14%). Median survival was 3 months (range, 1-17), and 1-year
      survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3
      asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic
      reactions in 2. No treatment-related death was recorded. CONCLUSIONS: The trial
      showed only very modest activity of weekly docetaxel, with severe side effects
      that induced us to stop the accrual in order to prevent other worse toxicities.
      We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not
      manageable and does not seem to provide a real benefit in terms of response and
      quality of life.

PMID- 15143974
TI  - Regionally advanced nasopharyngeal carcinoma: long-term outcome after sequential
      chemotherapy and radiotherapy.
AB  - AIMS AND BACKGROUND: To evaluate the long-term clinical outcome of 61 patients
      with regionally advanced nasopharyngeal carcinoma treated with sequential
      chemotherapy and radiotherapy within a phase II trial. METHODS: The trial
      evaluated a combined modality regimen including 3 cycles of induction
      polychemotherapy (epirubicin 70 mg/m2 d1, and cisplatin 100 mg/m2 d1, both
      recycled every 3 weeks) followed by definitive radiotherapy to the primary site
      (64-70 Gy) and the neck (50-70 Gy). Patients included in the trial had
      pathologically confirmed nasopharyngeal carcinoma; stage (UICC 1987) T-any, N2-3,
      M0; ECOG performance status 0-1. Sixty-one patients were enrolled between 1990
      and 1996; stage according to UICC 1997 was IIb in 8%, III in 36% and IV in 56% of
      the patients; histology was WHO type 1-2 in 11% and WHO type 3 in 89% of cases.
      Minimum follow-up of 33 surviving patients is 5.2 years. RESULTS: Clinical
      failure has been observed in 30 patients (49%): initial failure, observed within
      the third year of follow-up in all but one case, was local alone in 6 (20%),
      regional alone in 10 (33%), local and regional in 1 (3%), regional and distant in
      1 (3%), and distant alone in 12 patients (40%). Seven patients received salvage
      surgery to the neck, 2 of them still disease-free at 10 and 11 years from salvage
      surgery; 4 patients with an isolated local relapse were re-irradiated, and one of
      them was alive and well at 6.5 years from salvage radiation. At 5-year local
      control, regional control and distant metastasis-free rates were 83%, 74% and
      73%, respectively; overall and disease-free survival were 64% and 51%. Late
      effects of initial treatment, as evaluated in 30 patients surviving 5 years
      without relapse, were generally acceptable, but some degree of xerostomia, dental
      damage, trismus and hearing loss were reported by a significant proportion of
      patients (respectively 100%, 88%, 76% and 86%). CONCLUSIONS: In our experience,
      long-term clinical cure of regionally advanced nasopharyngeal carcinoma was
      obtained in 51% of cases treated with chemotherapy and radiotherapy. Salvage
      treatments (neck surgery, local re-irradiation) are worthy, as they increase the
      cure rate by approximately 10%, raising 5-year survival to over 60%. Late effects
      are significant, calling for refinements in radiation technique, better
      integration with chemotherapy to possibly decrease the need for higher radiation
      dose, and/or use of effective radioprotectants.

PMID- 15143973
TI  - Carboplatin and gemcitabine in the palliative treatment of stage IV non-small
      cell lung cancer: definitive results of a phase II trial.
AB  - BACKGROUND: Cisplatin-containing regimens represent the gold standard in the
      treatment of advanced non-small cell lung cancer, but carboplatin is often
      preferred for its better toxic profile when palliation is the aim of the
      treatment. The synergistic effect and tolerability of carboplatin-gemcitabine
      combination are well known. In this phase II trial, we evaluated the activity and
      safety of a schedule with carboplatin and gemcitabine, defined in our previous
      phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small
      cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and
      gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated
      until disease progression or intractable toxicity and were evaluated before each
      course of chemotherapy for toxicity and after every 3 courses for response.
      RESULTS: After a median follow-up of over 10 months, complete response, partial
      response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%),
      and 15 patients (40.5%), respectively. Median time to progression was 7 months.
      At this writing, 27 patients have died, with a median survival of 10 months, and
      29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15
      months of follow-up, respectively. Toxicity was mild, and mainly hematological,
      with a significant correlation with the number of courses of chemotherapy (P =
      0.0003). CONCLUSIONS: Our results are comparable with those reported in the
      literature and confirm the good activity and tolerability of the carboplatin
      gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and
      gemcitabine may represent an interesting option in the palliative treatment of
      non-small cell lung cancer.

PMID- 15143975
TI  - Contralateral parotid-sparing radiotherapy in patients with unilateral squamous
      cell carcinoma of the head and neck: technical methodology and preliminary
      results.
AB  - AIMS AND BACKGROUND: Radiation-induced permanent xerostomia occurs frequently in
      patients affected by squamous cell carcinoma of the head and neck treated by
      parallel opposed lateral fields. An ipsilateral technique by using co-planar
      multiple-field arrangement was designed to restrict treatment to the primary
      tumor and neck on the same side for patients with selected lateralized squamous
      cell carcinoma of the head and neck. METHODS: From November 2001 till December
      2002, 30 patients affected by squamous cell carcinoma of tonsillar fossa,
      retromolar trigone, alveolar ridge and oropharyngeal lateral wall were included
      in this investigational trial and treated with an ipsilateral multiple field
      technique: in detail, oblique opposed two upper half fields were planned
      ipsilaterally to the squamous cell carcinoma site to cover PTV1 and PTV2, whereas
      an anterior-lower half field was planned to encompass the lower neck node area
      above clavicles. On CT scans, the contralateral parotid gland was outlined as
      organ at risk and the contralateral upper lymph node area was contoured as volume
      of interest. In selected cases, convergent oblique two wedge-pair half fields
      were added to opposed oblique two-field technique in order to cover only PTV2:
      generally, in these patients, PTV1 received 1.8 Gy per fraction and PTV2 2.2 Gy
      per fraction up to total doses of 54 Gy and 66 Gy, respectively. RESULTS: Ten
      patients received radical radiotherapy, 9 patients radical alternating chemo
      radiotherapy, and 11 patients adjuvant radiotherapy. At the end of treatment,
      unilateral confluent mucositis was recorded in 13 (43%) patients and unilateral
      moist skin epidermolysis in 14 (46%) patients. Six months after the end of
      radiotherapy, grade 0 xerostomia was recorded in 20 (67%) patients. No patient
      experienced grade 2+ xerostomia. At a median follow-up of 12 months, 26 (86%)
      patients were alive and well; 2 patients (6%) developed contralateral neck node
      failure, both 4 months after the end of ipsilateral radiotherapy. CONCLUSIONS:
      These results, although preliminary, suggest that by using an ipsilateral
      radiotherapy technique, symptomatic xerostomia may be avoided in selected
      patients with lateralized squamous cell carcinoma of the head and neck without an
      increased short-term risk of contralateral nodal failure.

PMID- 15143976
TI  - Radiotherapy of liver malignancies. From whole liver irradiation to stereotactic
      hypofractionated radiotherapy.
AB  - AIMS AND BACKGROUND: Until recently radiotherapy of hepatic malignancies has
      played a limited role due to the well-known limited radiotolerance of the liver.
      The aim of this paper is to review the available data on the risk of radiation
      induced liver disease (RILD) and to define the modern role of radiotherapy in the
      management of patients with metastatic or primary liver malignancies. METHODS:
      The advent of three-dimensional conformal treatment planning with dose-volume
      histogram analysis has made the study of partial liver irradiation possible.
      Limited portions of the liver may withstand high doses of radiation with minimal
      risk of RILD. Patients with solitary unresectable liver tumors may be treated
      with high-dose radiotherapy with curative intent. Recently, the feasibility of
      stereotactically guided treatment techniques with a single fraction or few
      treatment sessions has been explored in numerous institutions. RESULTS: The
      radiation tolerance of the whole liver found by several investigations is in the
      order of approximately 30 Gy, which seriously restricts its clinical application.
      The role of whole liver irradiation therefore appears of limited benefit in the
      palliation of patients with multiple liver metastases. The use of three
      dimensional conformal techniques has made partial liver irradiation possible to
      doses in the 70-80 Gy range with conventional fractionation. At least two
      published series have reported improved local control and survival rates with
      dose escalation with three-dimensional conformal radiotherapy in patients with
      unresectable liver metastases. Similar outcomes have been recently reported with
      single dose (or hypofractionated) stereotactic radiotherapy both in metastatic
      and primary hepatic malignancies with minimal morbidity. Accurate target
      delineation and treatment reproducibility are the key to the success of this
      novel treatment approach, and specific treatment planning techniques and patient
      setup procedures must be developed to implement it. CONCLUSIONS: Stereotactic
      high-dose radiotherapy is technically feasible for the treatment of inoperable
      liver malignancies, with the potential of high local control and low morbidity.
      Definitive evidence on the clinical advantages of this technique over other more
      established treatments can only be gathered from well-designed clinical studies.

PMID- 15143977
TI  - Fractionations in radiotherapy of brain metastases.
AB  - AIMS AND BACKGROUND: The aim of this study was to evaluate different
      fractionations for radiotherapy of brain metastases. METHODS: One hundred and
      twenty-five patients treated with whole brain cobalt therapy (WBRT) were examined
      to evaluate the effect on survival and quality of life of three different dose
      fractionations (2 Gy x 25, 3 Gy x 10 and 4 Gy x 5). Fractionation was evaluated
      in relation to mean survival, single or multiple lesions, presence of
      extracranial metastases, primary tumor control and neurological status before and
      after treatment. Kaplan-Meier analysis of survival and univariate and
      multivariate analysis of these factors were performed. Twenty-six (21%) patients
      were treated with 2 Gy x 25, 48 patients (38%) with 3 Gy x 10 and 42 patients
      (33%) with 4 Gy x 5. The other 9 patients were treated with unusual
      fractionations. RESULTS: In 66% of patients an improvement in neurological status
      after radiotherapy was recorded. Patients with controlled primary tumors had a
      better mean survival, 8.6 months, if they had no extracranial metastases. The six
      month survival was 21% in the 4 Gy x 5 group, 36% in the 3 Gy x 10 group, and 21%
      in the 2 Gy x 25 group; the results for one-year actuarial survival were highly
      similar in the three fractionation groups (5%, 11% and 6%, respectively).
      CONCLUSIONS: The use of 5 x 4 Gy fractionation may be appropriate in lung cancer
      patients, where no significant difference in 6- and 12-month survival was
      observed with respect to the other fractionation groups despite the most
      unfavorable prognosis of these patients and the lower biological effectiveness of
      this fractionation with respect to the other schedules.

PMID- 15143978
TI  - External beam irradiation in the palliation of bone metastases: a practice
      analysis among Sicilian Departments of Radiation Oncology.
AB  - BACKGROUND: In the treatment of bone metastases, the choice of radiation
      fractionation, total radiation dose, delivery technique, and imaging studies
      before treatment varies among radiation oncologists. Surveys on this issue, using
      case scenarios, have been published by groups from Europe, North America, and
      Australia-New Zealand. Our objective was to analyze retrospectively the "real"
      practice in nine radiotherapy centers located in Sicily. METHOD: A questionnaire
      including 17 items was distributed to 30 practicing radiation oncologists working
      in seven departments of four Sicilian cities (Messina, Catania, Ragusa and
      Palermo) during a meeting of the Sicilian Division of the Associazione Italiana
      Radioterapia Oncologica (AIRO). Participants were asked to answer the questions
      using a card for every patient treated with external beam irradiation from 1
      January to 31 December, 2000. RESULTS: Six centers returned the questionnaires;
      332 cards were valuable for a total of 5644 responses. All six responding
      departments used linear accelerators for treatment delivery. The most common dose
      fractionation was 30 Gy in 10 fractions and the most common technique used was
      opposed parallel local fields. Before the start of irradiation a bone scan was
      performed in 325 of the 332 (98%) patients treated and CT and/or MRI was
      performed in 320 (96%); surprisingly, standard roentgenograms were used in only
      142 of 332 patients (42.8%). CONCLUSION: The "real" radiation practice for bone
      metastases in the region of Sicily confirms the results of the previously
      reported international surveys: there is a clear preference for fractionated
      treatment and local field therapy. The results of randomized studies, which
      demonstrated both the efficacy and the feasibility of a single 6-8 Gy fraction in
      the palliation of bone metastases, have little or no impact on the pattern of
      practice.

PMID- 15143979
TI  - Comparative evaluation of two hypofractionated radiotherapy regimens for painful
      bone metastases.
AB  - AIMS AND BACKGROUND: In 75% of the patients with bone metastases (BM) pain is the
      dominant symptom. Radiotherapy (XRT) plays a major role in the palliation of pain
      in patients with BM. Several schedules of short and long fractionation XRT are
      used in clinical practice, with hypofractionated treatments being even more
      attractive for practical reasons. A considerable body of evidence supports the
      clinical use of short schedules and single-dose XRT. We retrospectively evaluated
      the efficacy of two short fractionated schedules of 8 Gy as a single dose and 20
      Gy in 5 fractions in relieving pain in patients with multiple uncomplicated BM.
      METHOD: From January to December 2001, 130 patients with 146 painful BM were
      treated with palliative localized XRT. There were 42 males and 88 females with a
      median age of 58 years (range 28-84). The commonest sites of treatment were the
      spine (59.6%) and pelvis (14.4%). The primary endpoint was clinically significant
      pain relief in the first six months of follow-up evaluated with the IAEA
      (International Atomic Energy Agency) pain measurement score measuring pain
      severity and pain frequency. Analgesic use was also recorded before and after
      treatment as drug frequency and drug severity. Patients with painful BM from any
      primary tumor site were irradiated. Treatment schedules consisted of a course of
      XRT with 4 Gy/fraction/day (total dose: 20 Gy/5 fractions) (group A, 59 lesions)
      or with a single dose of 8 Gy (group B, 87 lesions). RESULTS: There was no
      significant difference in complete response (CR) rates between treatment
      schedules: complete pain relief was achieved in 17/59 lesions (29%) in the
      fractionated group and in 29/87 lesions (33%) in the single-dose group. Also the
      overall response (complete + partial) was similar: 35/59 lesions (60%) in group A
      and 60/87 (69%) in group B. The minimum, maximum and median follow-up was 3, 23,
      and 9 months, respectively, for group A and 3, 20, and 11 months for group B. The
      actuarial median duration of pain relief was similar: 4.5 months in group A and 4
      months in group B. No particular side effects were recorded in either group.
      CONCLUSIONS: There were no differences between the two fractionation schedules
      used in our study with regard to pain relief and use of analgesics. Palliation of
      pain was obtained in approximately two thirds of patients with both schedules,
      providing further evidence of the similar efficacy between single and multiple
      fractions. With regard to pain response these data justify a recommendation for
      the use of a more simple and convenient 8 Gy single fraction for the palliation
      of uncomplicated BM.

PMID- 15143980
TI  - Opioid consumption in hospitals of the Friuli-Venezia Giulia region: a four-year
      retrospective study.
AB  - AIMS AND BACKGROUND: Opioid consumption for analgesic purposes is considered an
      important indicator of the quality of cancer pain treatment. Italy's consumption
      ranks among the lowest in economically developed countries. A lack of systematic
      education of health care professionals regarding pain control and a sort of
      "opiophobia" induced by measures designed to control the improper use of drugs
      have been indicated as possible reasons for this trend. The aim of this study was
      firstly to evaluate the level of opioid consumption at inpatient institutions
      (where opioid prescription rules have never been subjected to any restriction)
      and secondly to survey the attitude of the physicians working in general
      hospitals and specialized oncology institutions (oncology centers and hospices)
      towards opioid administration. METHODS: The authors performed a four-year survey
      (1996-1999) on the consumption of major opioids (morphine, meperidine,
      buprenorphine, transdermal fentanyl) among all the inpatient institutions (six
      regional/provincial hospitals, eleven district hospitals, the Aviano Oncology
      Institute and two hospices) of the Friuli-Venezia Giulia region in North-Eastern
      Italy. To facilitate data interpretation, all the opioids were converted to
      milligrams equivalent of oral morphine (mg OME). Data on the number of days of
      hospitalization of oncological patients in every institution were also collected.
      RESULTS: The overall consumption of opioids was 9,299,177 mg OME (83.3%) and
      1,845,060 mg OME (16.7%) in general hospitals and specialized oncology
      institutions, respectively. Overall, the number of days of hospitalization of
      oncological patients was 1,121,142 (87%) and 167,665 (13%) in general hospitals
      and specialized oncology institutions, respectively. The ratio between the total
      dosage of mg OME administered and the total number of hospitalization days in
      general hospitals and specialized oncology institutions was 8.29 mg OME/day and
      11 mg OME/day, respectively. CONCLUSIONS: Our data show that in specialized
      oncology institutions, opioid consumption was proportionally higher than in
      general hospitals. This result indicates the attitude of the physicians of these
      institutions towards opioid administration, probably due to the training received
      on cancer pain treatment, and emphasizes the need to educate all health care
      workers involved in the management of cancer patients.

PMID- 15143981
TI  - Cancer patients submitted to innovative chemotherapeutic agents of intermediate
      emetogenic potential: antiemetic prescriptions and incidence of emesis.
AB  - Controversies exist regarding the classification of the emetogenic potential of
      chemotherapeutic agents such as taxanes, gemcitabine and irinotecan and the
      antiemetic prophylaxis for acute emesis to be administered. Instead, no
      prophylaxis for delayed emesis has been suggested. A prospective, observational
      study was carried out in 103 Italian oncological centers to evaluate the
      prescriptions of antiemetics and the incidence of nausea and vomiting in patients
      submitted to these chemotherapy agents. Two hundred and nine patients treated
      with taxanes, 300 with gemcitabine and 93 with irinotecan were evaluated. For the
      prophylaxis of acute emesis a 5-HT3 antagonist alone or in combination with a
      corticosteroid was administered to 86.6% of patients receiving taxanes, to 59.3%
      of those receiving gemcitabine and to 96.8% of those submitted to irinotecan. 20%
      to 40% of patients received antiemetic prophylaxis for delayed emesis. In taxane
      treated patients the incidence of acute vomiting and nausea was 6.2% and 27.3%,
      respectively, while in gemcitabine- and irinotecan-treated patients it was
      6.0/33.4% and 17.9/58.9%, respectively. In conclusion, the study showed that
      almost all patients received prophylaxis for acute emesis and that there is
      overprescription of 5-HT3 antagonists. The incidence of acute emesis is low;
      therefore, randomized clinical trials are necessary to verify the utility of
      prophylaxis and to find the best antiemetic treatment.

PMID- 15143982
TI  - The importance of extracapsular extension of axillary lymph node metastases in
      breast cancer.
AB  - PURPOSE: To evaluate the prognostic value of extracapsular extension (ECE) of
      axillary lymph node metastases in 221 patients with axillary lymph node-positive,
      T1-T2 breast cancer treated at Dokuz Eylul University Hospital, Department of
      Radiation Oncology. PATIENTS AND METHODS: The clinical records of patients with
      axillary node-positive, pathological stage II-III breast cancer examined at Dokuz
      Eylul University Hospital, Department of Radiation Oncology, between 1991-1999
      were reviewed. All patients underwent modified radical mastectomy (MRM) or wide
      excision with axillary node dissection. Axillary surgery consisted of level I-II
      dissection. The number of lymph nodes dissected from the axilla was equal to or
      more than 10 in 92% of the patients. All 221 patients had pathological T1-T2
      tumors. The number of involved lymph nodes was four or more in 112 51% patients
      and less than four in the remaining 109 (49%). In 127 (57.5%) patients,
      extracapsular extension was detected in axillary lymph nodes. Tangential
      radiotherapy fields were used to treat the breast or chest wall. Lymphatic
      irradiation was performed in 215 (97%) patients with fields covering both the
      supraclavicular and axillary regions. Median radiotherapy dose for lymph nodes
      was 5000 cGy in 25 fractions. The following factors were evaluated: age,
      menopausal status, histological tumor type, pathological stage, number of
      involved axillary lymph nodes, and extracapsular extension. The chi-square test
      was used to compare proportions of categorical covariates between groups of
      patients with and without ECE. Survival analyses were estimated with the Kaplan
      Meier method. The Cox regression model was used for the analysis of prognostic
      factors. RESULTS: The median follow-up for the survivors was 55 months (range, 19
      23). The median age was 52 years (range, 28-75). In patients with extracapsular
      extension the percentages of pathological stage III (22% vs 4.3%, P < 0.0001 and
      involvement of four or more axillary nodes (25.5% vs 69.3%, p < 0.0000) were
      higher. Multivariate analysis revealed a significant correlation between the
      presence of ECE and disease-free survival (DFS) (P = 0.04) as well as distant
      metastases-free survival (DMFS) (P = 0.002), but there was no significant
      correlation between ECE and overall survival (OS). Only an elevated number of
      involved axillary lymph nodes significantly reduced the overall survival (P =
      0.001). CONCLUSION: The rate of extracapsular extension was found to be directly
      proportional to the number of axillary lymph nodes involved and the stage of
      disease. Extracapsular extension had significant prognostic value in both
      univariate and multivariate analysis for DFS and DMFS but not OS. The reason for
      ECE not affecting OS might be related to the much more dominant prognostic effect
      of the involvement of four or more axillary nodes on OS. Studies with more
      patients are needed to demonstrate that ECE is a likely independent prognostic
      factor for OS.

PMID- 15143983
TI  - Prognostic value of different factors in breast carcinoma.
AB  - INTRODUCTION: The aggressive biological behavior of invasive and metastatic
      cancer is considered to be the most insidious and life-threatening aspect for
      breast cancer patients. It is mostly the result of changes in many molecular
      characteristics of tumor cells, including alterations in the mechanisms
      controlling cell growth and proliferation. AIM: The aim of this retrospective
      study was to identify predictors of aggressive biological behavior and metastatic
      potential in breast carcinoma among a number of intrinsic biomarkers of tumor
      cells such as steroid receptors and oncogene and tumor suppressor gene products.
      METHODS: Routine formalin-fixed, paraffin-embedded tumor samples were used and
      sections were stained immunohistochemically with the DAKO Strept ABC method to
      determine the expression of estrogen receptors (ER), progesterone receptors
      (PgR), HER-2/neu, bcl-2, Ki-67, p53 and nm23 in 192 consecutive breast carcinoma
      patients. The results of the quantitative immunohistochemical assays were
      correlated with clinical and histological data such as patient age, overall
      survival, tumor size, axillary lymph node status, hystological type, tumor grade,
      Nottingham prognostic index (NPI) and therapeutic regimens. RESULTS: Univariate
      analysis revealed that survival was significantly longer for patients with small
      tumors (P = 0.007), lower tumor grade (P = 0.021), negative axillary lymph nodes
      (P = 0.002), presence of nm23 protein (P = 0.002), and for patients treated with
      adjuvant hormonal therapy (P = 0.010). In multivariate analysis the independent
      factors positively affecting survival were absence of axillary lymph node
      metastases (P = 0.002), nm23 expression (P = 0.009) and hormonal therapy (P =
      0.050). Among patients with positive axillary nodes there was a significantly
      higher survival rate in patients with nm23 expression compared with nm23-negative
      patients (P < 0.001). CONCLUSION: Identification of a subset of node-positive
      breast cancer patients with a more favorable prognosis according to nm23
      expression might be clinically useful.

PMID- 15143985
TI  - Micro-melanoma detection. A clinical study on 22 cases of melanoma with a
      diameter equal to or less than 3 mm.
AB  - BACKGROUND AND AIMS: Very small pigmented lesions may represent an extreme
      diagnostic challenge to the clinician. Our aim was to describe the clinical and
      dermoscopic features in a series of cutaneous melanomas with a maximum clinical
      diameter of 3 mm. METHODS: We conducted a retrospective study of the 924 primary
      melanomas seen and treated during a period of five years at the Unit for Melanoma
      Detection of the Istituto Nazionale Tumori of Milan, Italy. The size
      characteristics of the considered lesions allowed the identification of 22 (2.4%)
      cases of micro-melanoma (clinical diameter of 3 mm or less). Sixteen of these
      cases were subjected to dermoscopy. The clinical and dermoscopic features as well
      as the corresponding diagnoses were recorded. RESULTS: The typical lesion
      presents as a small, dark, often black macule, generally evenly colored, with
      well-defined borders; it may be asymmetric or symmetric in shape. These features
      prompted a correct clinical diagnosis in nearly half of the cases. Dermoscopy
      lead to a correct diagnosis in all cases subjected to the technique. CONCLUSION:
      Dermoscopy appears to be an efficient aid to the diagnosis of micro-melanomas,
      provided that clinicians are aware of this type of lesion and maintain the index
      of suspicion at a high level.

PMID- 15143984
TI  - p53 protein expression and cell proliferation in non-neoplastic and neoplastic
      proliferative skin diseases.
AB  - AIMS AND BACKGROUND: The p53 protein is essential for the regulation of cell
      proliferation and its aberrant accumulation is usually seen in malignant tumors
      but also occurs in squamous epithelium of inflammatory skin diseases
      characterized by hyperproliferation. The aim of this study is to elucidate the
      role of the p53 tumor suppressor protein in the pathogenesis of different
      hyperproliferative, non-malignant and malignant skin diseases, and to determine
      the association between p53 overexpression and cell proliferation. We also
      investigated the influence of aging on p53 and Ki-67 protein expression. METHODS:
      One hundred and fifty skin specimens divided into 30 samples each of normal skin
      (NS), psoriatic skin (PS), keratoacanthomas (KA), basal cell carcinomas (BCC),
      and squamous cell carcinomas (SCC) were examined immunohistochemically to assess
      p53 and Ki-67 protein expression. RESULTS: p53 immunostaining of NS, PS, KA, BCC
      and SCC was detected in 39.0%, 46.7%, 66.7%, 80% and 86.7% of cases,
      respectively. Median values and ranges of p53 protein expression were as follows:
      0.0% (range, 0.0-1.8%) in NS, 0.0% (range, 0.0-6.5%) in PS, 9.2% (range, 0.0
      24.0%) in KA, 19.3% (range, 0.0-48.1%) in BCC and 30.1% (range, 0.0-68.1%) in
      SCC. p53- and Ki-67-positive cells were present in basal (NS) and suprabasal
      layers (PS), and not only in cancer nests of KA, BCC and SCC but also in
      dysplastic and even morphologically normal epidermis adjoining cancers. The
      positivity of p53 and Ki-67 proteins differed significantly among the groups,
      with no differences in p53 expression between NS and PS and in Ki-67 expression
      between PS and KA. Within all groups there was a significant correlation between
      p53 and Ki-67 expression. Lesion location and patient age, with the exception of
      location in PS and age in BCC, were significantly related to p53 and Ki-67
      expression in all groups. CONCLUSIONS: Our findings suggest that p53
      overexpression occurs mainly in neoplastic skin lesions, although it may also
      occur in squamous epithelium of inflammatory skin diseases such as PS, as well as
      in normal skin epithelium. It is associated with cell proliferation in normal as
      well as altered epithelium. p53 protein overexpression is an age-related process
      and significantly associated with sun exposure, especially in NS and PS but also
      in KA and SCC. Our findings suggest that Ki-67 rate and p53 protein expression
      reflect the degree of malignancy in the examined cutaneous neoplasms.

PMID- 15143986
TI  - The development of pulmonary adenocarcinoma in a patient with Job's syndrome, a
      rare immunodeficiency condition.
AB  - The hyperimmunoglobulin E (HIE) (Job's) syndrome often has it onset in childhood
      and is characterized by markedly elevated serum IgE levels, chronic dermatitis
      and recurrent pyogenic infections. Lymphoid malignancies have most commonly been
      associated with this syndrome while the first case in the literature of carcinoma
      associated with HIE syndrome was a squamous cell carcinoma of the vulva,
      described by Clark et al. in 1998. We observed a male patient with Job's syndrome
      diagnosed at age three who presented with bone pain and a metastatic epithelial
      tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting
      the primary site showed multiple mediastinal lymph nodes with lung and liver
      metastases on computed tomography scans and an extradural spinal metastasis at
      the upper thoracic level on magnetic resonance imaging. Although the patient
      refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was
      established on the basis of sputum cytology and the clinical aspects of tumor
      extent. Intravenous corticosteroids and palliative radiotherapy were given for
      the spinal metastasis. Palliative chemotherapy could not be started because of
      the patient's poor performance status as well as nosocomial fungal pneumonia and
      pseudomonal urogenital infection with bacteremia. Despite the antifungal and
      broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.

PMID- 15143987
TI  - Primary pure ovarian choriocarcinoma mimicking ectopic pregnancy: a report of
      fulminant progression.
AB  - Nongestational choriocarcinoma of the ovary is a germ cell tumor with a worse
      prognosis than gestational choriocarcinoma. In this report we present a
      nongestational choriocarcinoma that was referred to our hospital as an ectopic
      pregnancy. The clinical features, management, and outcome are discussed.

PMID- 15143988
TI  - Case report of a hepatic angiomyolipoma.
AB  - Angiomyolipoma (AML) is a benign mesenchymal tumor that has been frequently
      reported in the kidney but rarely in the liver. Hepatic AML may be clinically,
      radiologically and morphologically difficult to distinguish from hepatocellular
      carcinoma or other hepatic lesions, even though the number of cases has been
      increasing recently due to improved imaging techniques. Histologically it
      consists of smooth muscle cells, adipose cells and abnormal blood vessels. It is
      commonly diagnosed following abdominal pain but may also be asymptomatic, has a
      predominant female predilection, highly variable size and occurs in subjects with
      a wide age range. The right lobe is the most common site, and multicentricity has
      been reported. Here we report a case of the myomatous variant of AML,
      accidentally discovered in a young woman with no clear features on radiographic
      examination, which was diagnosed by means of fine needle aspiration biopsy (FNAB)
      and then surgically removed. Although careful observation with serial
      radiological follow-up is an option in these cases, we chose the surgical
      approach because of the risk of rupture due to the large size of the lesion and
      the risk of malignant behavior or transformation. In case of the myomatous
      variant composed of irregular cells with epithelioid appearance, hepatocellular
      carcinoma with fatty changes or the possibility of other malignant tumors must be
      ruled out by immunohistochemistry (HMB-45), even in biopsy specimens.

PMID- 15143989
TI  - Spontaneous splenic rupture after the start of lung cancer chemotherapy. A case
      report.
AB  - Hamartoma of the spleen, first described by Rokitansky in 1861 under the name of
      "splenoma", is a rare benign lesion that is nearly always asymptomatic. Apart
      from the congenital forms there are also acquired forms of splenoma that are
      frequently associated with hematological diseases or solid tumors. We describe
      the case of a man suffering from splenoma who had a spontaneous rupture of the
      spleen with serious hemoperitoneum a few hours after the start of
      polychemotherapy for squamous cell lung cancer. The close temporal relationship
      with the event led us to suspect that the drugs used (cisplatin, vinorelbine and
      corticosteroids) could have played a causal role. From a review of the literature
      this seems to be the third case reported of spontaneous rupture of the spleen
      with hamartoma, and the first with the concomitant occurrence of lung cancer.

PMID- 15143990
TI  - Meningeal hemangiopericytoma metastatic to the adrenal gland with multiple
      metastases to bones and lungs: a case report.

PMID- 15143991
TI  - Mediastinal chondrosarcoma.
AB  - The authors report a rare case of primary chondrosarcoma of the anterior
      mediastinum showing unusual pathological and clinical features, namely 1) the
      lack of any anatomical relationship between the tumor and cartilage-containing
      organs, and 2) an indolent behavior with long-term survival. In spite of early
      disease recurrence and repeated surgery, the patient is in good health five years
      after primary surgery. The reported case suggests that 1) primary chondrosarcomas
      of the anterior mediastinum may have a better prognosis than previously
      recognized, 2) the disease can remain confined within the chest for as long as
      five years, and 3) repeated surgery may contribute to long-term survival.

PMID- 15143992
TI  - Paraneoplastic nephrotic syndrome in advanced breast cancer patient. A case
      report.
AB  - A case of paraneoplastic nephrotic syndrome (NS) is described five years after
      the diagnosis of breast cancer. A review of the literature shows that NS is a
      rare complication of breast carcinoma.

PMID- 15143994
TI  - The tobacconist boutique, an inviting (and misleading) marriage between smoking
      and culture.

PMID- 15143993
TI  - Gliofibroma: an incompletely characterized tumor.
AB  - Although gliofibroma is a rare and incompletely characterized tumor, recent
      publications have revealed new aspects of this entity. The case of a 16-year-old
      boy who was diagnosed as having a gliofibroma is presented here, and the problems
      regarding nosology are discussed in the light of the recent literature.

PMID- 15143995
TI  - [San Antonio Breast Cancer Symposium 2003. New therapeutic prospects in the
      treatment of early-stage breast cancer].

PMID- 15143996
TI  - [Oral capecitabine therapy: experience and developments at the Milano Cancer
      Institute].

PMID- 15143998
TI  - Increased funding to tackle diseases of livestock.

PMID- 15143997
TI  - [January 2004: a month of success with oxaliplatin and hope for patients with
      colorectal cancer].

PMID- 15143999
TI  - Risk factors associated with the prevalence of interdigital dermatitis in sheep
      from 1999 to 2000.
AB  - As part of an investigation into improving the treatment and control of lameness
      in sheep flocks in England and Wales, a postal survey was conducted in November
      2000. Farmers were asked to estimate the prevalence of footrot and interdigital
      dermatitis in their flocks. In the ewes the prevalence of interdigital dermatitis
      remained relatively stable throughout the year, but there was a large increase in
      lambs during late spring and early summer. Logistic regression models were used
      to assess statistically significant risk factors associated with prevalences of
      the condition of 5 per cent or more in ewes and 10 per cent or more in lambs.
      Factors that increased the risk in ewes were 'sometimes/never' catching lame
      sheep compared with 'always' farm land 100 m or less above sea level and renting
      in winter grazing; factors that increased the risk in lambs were a prevalence of
      5 per cent or more of footrot in ewes, 'sometimes/never' catching lame ewes
      compared with 'always', 'sometimes/never' treating ewes with footrot with
      parenteral antibiotics compared with 'always', showing sheep at agricultural
      events, farm land 100 m or less above sea level, and a prevalence of 5 per cent
      or more of interdigital dermatitis in ewes. Turning sheep on to a field which had
      been free from livestock for at least two weeks after footbathing decreased the
      risk of interdigital dermatitis in lambs. Footbathing without the use of a clean
      field compared with not footbathing did not significantly affect the prevalence
      of the interdigital dermatitis.

PMID- 15144000
TI  - Effects of stocking density and group size on the condition of the skin and
      feathers of pheasant chicks.
AB  - Twenty-two flocks of pheasants were reared from day-old to approximately six
      weeks of age without the use of beak trimming or other measures against feather
      pecking. The pheasants were housed in aviaries in groups of 80 or 240 chicks at
      stocking densities of 0.7, 1.3 or 4.0 birds per m2. The quality of the pheasants'
      plumage was poorer at the highest stocking density than at the two lower
      densities. Higher stocking densities resulted in higher proportions of birds with
      injuries to their skin (7.2 per cent, 13 per cent and 34 per cent). The group
      size had no significant effect on the quality of the birds' plumage, but at the
      largest group size there were significantly more beak-inflicted skin injuries (21
      per cent v 12 per cent). In the period between 35 and 42 days of age, the quality
      of the birds' plumage decreased significantly.

PMID- 15144001
TI  - Comparative pathology of parasitic infections in free-ranging and captive pit
      vipers (Bothrops jararaca).
AB  - Between June 1997 and May 1998, 47 pit vipers (Bothrops jararaca) (Group A) were
      euthanased when they were brought to the Instituto Butantan by farmers, and
      examined postmortem; during the same period, 91 snakes of the same species (group
      B) were examined after they had died in an outdoor serpentarium. The majority of
      the parasites encountered were nematodes; lungworms, Rhabdias vellardi, and the
      intestinal hookworm Kalicephalus inermis were the most common. Some of the snakes
      in group A were heavily infested, but their lesions were mild, whereas in group B
      the parasites were generally accompanied by severe lesions. The parasites with a
      direct life cycle were more common than those with obligatory intermediate hosts,
      and the snakes were more commonly infected during the hotter and more humid
      seasons.

PMID- 15144002
TI  - Left perinephric abscess associated with nephrolithiasis and bladder calculi in a
      bitch.
AB  - An eight-year-old, entire female Pekingese cross, weighing 3.8 kg, had been
      inappetent with fever, depression, abdominal pain, vomiting and diarrhoea for
      seven days. The radiographic and ultrasonographic findings were consistent with
      glomerulonephritis, nephrolithiasis in both kidneys, bladder calculi and an
      accumulation of fluid in the left perinephric space. The clinical signs, together
      with the results of the diagnostic imaging, suggested that this fluid could be
      pus. A definitive diagnosis of a subcapsular abscess in the left kidney was
      established when this kidney was removed surgically. A histopathological
      examination of the kidney revealed a diffuse suppurative interstitial nephritis,
      membranous glomerulonephritis and an abscess invading the perinephric adipose
      tissue from the renal cortex. Twelve months after surgery the dog remains
      clinically stable, but owing to the disease of its remaining kidney its long-term
      prognosis is poor.

PMID- 15144004
TI  - First case of Thelazia callipaeda infection in a dog in Germany.

PMID- 15144003
TI  - Investigation of attaching and effacing activity of ruminant eae-positive
      Escherichia coli using rabbit and lamb ligated ileal loop assays.

PMID- 15144005
TI  - Lifetime reproductive performance of sows kept indoors and outdoors in Croatia.

PMID- 15144006
TI  - Detection of Coxiella burnetii by immunomagnetic separation-PCR in the milk of
      sheep in Turkey.

PMID- 15144007
TI  - Competition in the supply of medicines.

PMID- 15144008
TI  - Funding animal health and welfare.

PMID- 15144010
TI  - Alimentary tract perforation in cattle caused by tyre wire.

PMID- 15144009
TI  - Off-label treatment for otoacariosis.

PMID- 15144011
TI  - Necrotic enteritis in mute swans associated with cyanobacterial toxins.

PMID- 15144012
TI  - Ornithonyssus bacoti infestation on pets in the UK.

PMID- 15144013
TI  - Call for veterinary historians.

PMID- 15144014
TI  - Analysis of the IDDM candidate gene Prss16 in NOD and NON mice.
AB  - The thymus-specific serine protease Prss16 is highly expressed by the epithelial
      cells in the thymic cortex. It has been suggested to play an important role in
      the positive selection of T cells through the antigen presention pathway of the
      cortical antigen presenting cells. Recently, the gene encoding Prss16 has been
      linked to insulin dependent diabetes mellitus (IDDM) susceptibility independent
      of HLA-DR3 suggesting the Prss16 may be involved in the development of autoimmune
      disease. Due to the similarities of the gene structure and expression pattern
      between the human and mouse genes, we compared Prss16 between non-obese diabetic
      (NOD) and non-obese non-diabetic (NON) mice. Analysis of the Prss16 coding region
      failed to identify any differences in sequence. Northern analysis and semi
      quantitative reverse transcriptase polymerase chain reaction showed that the mRNA
      was equal in size and abundance in the two strains. In situ hybridization showed
      similar patterns of staining. Therefore, our data suggests that there is no
      significant different in the gene structure, transcription level, and expression
      pattern of Prss16 gene between NOD and NON mice.

PMID- 15144015
TI  - Marginal zone B cells in neonatal rats express intermediate levels of CD90 (Thy
      1).
AB  - Here we show that marginal zone (MZ)-B cells in rats can already be detected in
      neonatal spleen from two days after birth. At this time point, morphologically
      distinct MZs are not present yet and the vast majority of B cells in spleen are
      located in a concentric area surrounding the T cell zones (PALS). Before MZs are
      obviously detectable in spleen (14 days after birth), MZ-B cells seem to be
      enriched at the outer zones of the concentric B cell areas. Similar to adult
      rats, neonatal MZ-B cells are intermediate-sized cells that express high levels
      of surface (s)IgM and HIS57 antigen, and low levels of sIgD and CD45R (HIS24). We
      show here, however, that in contrast to adult MZ-B cells, MZ-B cells (and also
      recirculating follicular (RF)-B cells) in neonatal rats express higher levels of
      CD90 (Thy-1). In adult rats, expression of CD90 on the B cell lineage is confined
      to immature B cells. We speculate that the expression of CD90 on neonatal MZ-B
      cells may have implications for their responsiveness to polysaccharide (T cell
      independent type 2) antigens.

PMID- 15144016
TI  - T cells of different developmental stages differ in sensitivity to apoptosis
      induced by extracellular NAD.
AB  - Extracellular nucleotides such as ATP and NAD can profoundly affect the functions
      of lymphocytes, macrophages, and other cells. We have recently shown that
      extracellular NAD induces rapid apoptosis in naive T cells by a mechanism
      involving the ADP-ribosylation of cell surface molecules. In the present paper,
      we describe that T cells of different developmental stages differ in their
      sensitivity to NAD-induced apoptosis. Thymocytes were less susceptible than
      peripheral lymph node T cells, and freshly activated cells were more resistant
      than resting cells. Sensitivity to NAD-induced apoptosis generally correlated
      with expression of the ADP-ribosyltransferase ART2.2, which is not expressed on
      thymocytes and shed from peripheral T cells upon activation. Our findings suggest
      that NAD-induced apoptosis does not play a role during thymic selection of T
      cells, but rather may play a role by preventing the activation of unwanted
      bystander T cells during an immune response, and thus may participate in the
      control of autoimmunity.

PMID- 15144017
TI  - Conclusions from two model concepts on germinal center dynamics and morphology.
AB  - Germinal centers (GC) are an essential part of the humoral immune response. They
      develop a clear structure during maturation: Centroblasts and centrocytes are
      separated into two zones, the dark and the light zone. The mechanisms leading to
      this specific morphology as well as the reason for zone-depletion during a later
      phase of the GC reaction have not clearly been revealed in experiment. We discuss
      and weigh possible mechanisms of dark and light zone development in the framework
      of two mathematical models. In a comparative approach we formulate constraints on
      typical lymphocyte velocities in GCs which are characteristic for the different
      proposed mechanisms.

PMID- 15144018
TI  - Proliferative responses of harbor seal (Phoca vitulina) T lymphocytes to model
      marine pollutants.
AB  - In recent years, population declines related to viral outbreaks in marine mammals
      have been associated with polluted coastal waters and high tissue concentrations
      of certain persistent, lipophilic contaminants. Such observations suggest a
      contributing role of contaminant-induced suppression of cell-mediated immunity
      leading to decreased host resistance. Here, we assessed the effects of the
      prototypic polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (B[a]P), and two
      polychlorinated biphenyls (PCBs), CB-156 and CB-80, on the T-cell proliferative
      response to mitogen in harbor seal peripheral lymphocytes. Despite the
      variability associated with our samples from free-ranging harbor seals, we
      observed a clear suppressive effect of B[a]P (10 uM) exposure on T cell
      mitogenesis. Exposures to 10 uM CB-156 and CB-80, and 1.0 and 0.1 uM B[a]P, did
      not produce significant depression in lymphoproliferation. Exposure to the model
      PAH at 10 uM resulted in a 61% (range 34-97%) average reduction in
      lymphoproliferation. We were able to rule out a direct cytotoxic effect of B[a]P,
      indicating that observed effects were due to altered T cell function. Based on
      our in vitro results, we hypothesize that extensive accumulation of PAH by top
      trophic-level marine mammals could alter T cell activation in vivo and impaired
      cell-mediated immunity against viral pathogens.

PMID- 15144020
TI  - The dynamics of germinal centre selection as measured by graph-theoretical
      analysis of mutational lineage trees.
AB  - We have developed a rigorous graph-theoretical algorithm for quantifying the
      shape properties of mutational lineage trees. We show that information about the
      dynamics of hypermutation and antigen-driven clonal selection during the humoral
      immune response is contained in the shape of mutational lineage trees deduced
      from the responding clones. Age and tissue related differences in the selection
      process can be studied using this method. Thus, tree shape analysis can be used
      as a means of elucidating humoral immune response dynamics in various situations.

PMID- 15144019
TI  - Early steps of a thymic tumor in SV40 transgenic mice: hyperplasia of medullary
      epithelial cells and increased mature thymocyte numbers disturb thymic export.
AB  - Bone marrow progenitors migrate to the thymus, where they proliferate and
      differentiate into immunologically competent T cells. In this report we show that
      mice transgenic for SV40 T and t antigens under the control of the L-pyruvate
      kinase promoter develop, in a first step, thymic hyperplasia of both thymocytes
      and epithelial cells. Morphological studies (histology, immunohistolabeling and
      electron microscopy) revealed modifications of the thymic microenvironment and
      gradual expansion of medullary epithelial cells in 1 month-old mice, taking over
      the cortical region. Then, a thymic carcinoma develops. Two-color labeling of
      frozen sections identified the transgene in medullary epithelial cells. Flow
      cytometry analysis demonstrated a marked increase in mature CD4+ and CD8+
      thymocytes in adult mice (39 +/- 10 x 10(6) in transgenic mice and 12 +/- 5 x
      10(6) in age-matched controls). Furthermore, thymocyte export was disturbed.

PMID- 15144021
TI  - Do bovine lymphocytes express a peculiar prion protein?
AB  - The cellular prion protein (PrPc) is a glycolipid-anchored cell surface protein
      that usually exhibits three glycosylation states. Its post-translationally
      modified isoform, PrPsc, is involved in the pathogenesis of various transmissible
      spongiform encephalopathies (TSEs). In bovine species, BSE infectivity appears to
      be restricted to the central nervous system; few or no detectable infectivity is
      found in lymphoid tissues in contrast to scrapie or variant CJD. Since expression
      of PrPc is a prerequisite for prion replication, we have investigated PrPc
      expression by bovine immune cells. Lymphocytes from blood and five different
      lymph organs were isolated from the same animal to assess intra- and
      interindividual variability of PrPc expression, considering six individuals. As
      shown by flow cytometry, this expression is absent or weak on granulocytes but is
      measurable on monocytes, B and T cells from blood and lymph organs. The
      activation of the bovine cells produces an upregulation of PrPc. The results of
      our in vitro study of PrPc biosynthesis are consistent with previous studies in
      other species. Interestingly, western blotting experiments showed only one form
      of the protein, the diglycosylated band. We propose that the glycosylation state
      could explain the lack of infectivity of the bovine immune cells.

PMID- 15144022
TI  - Implementation of the European Laryngological Society (ELS) basic protocol for
      assessing voice treatment effect.
AB  - OBJECTIVES: 93 patients with various kinds of organic benign voice pathology
      (vocal fold nodules, polyp, Reinke's oedema, unilateral paralysis, sulcus/scar)
      and/or with muscle tension dysphonia, were evaluated before and after their voice
      treatment (phonosurgery with voice therapy, antireflux medication, or voice
      therapy alone) in order to check the clinical relevance of a basic
      multidimensional protocol for assessing functional results of voice treatments,
      as developed by the Committee on Phoniatrics of the ELS. MATERIAL AND METHOD: The
      protocol has been used in different university voice clinics. It comprises 5
      dimensions: Perception: Grade, Breathiness and Roughness from the GRBAS-scale,
      rated by two experienced judges: a phoniatrician/laryngologist and a speech
      therapist. Acoustics: Jitter % and Shimmer % computed on a /a:/, at comfortable
      loudness and pitch. Also Fo-range and softest possible intensity.
      Videostroboscopy: Glottal closure, regularity, mucosal wave and symmetry, rated
      separately. Phonation quotient: computed by dividing the vital capacity (ml) by
      the maximum phonation time (s) (best value of 2x3 trials). Self rating by the
      patient: voice quality in itself and general social/occupational handicap due to
      the voice problem rated separately. RESULTS: Results show that, at group level,
      the overall effects for each parameter indicate a significant improvement after
      treatment. However, the correlations between the pre/post changes for the
      different parameters are weak (low redundancy). CONCLUSION: The assessment of
      voice pathology needs to be multidimensional, as these multidimensional
      informations about voice changes lead to a better understanding of the actual way
      in which a treatment works.

PMID- 15144023
TI  - Efficacy of voice therapy assessed with the Voice Range Profile (Phonetogram).
AB  - INTRODUCTION: Voice Range Profile (VRP), or Phonetography, is a widely used
      method of acoustic voice assessment: it explores and documents the extreme
      possibilities or capabilities of the voice by producing a chart displaying the
      intensity dynamics as a function of the fundamental frequency range. OBJECTIVES:
      In the present study VRP is used for investigating the efficacy of (isolated)
      functional voice therapy, and for defining the best suited VRP criteria for this
      purpose. MATERIAL AND METHOD: 30 adult voice patients with complaints of chronic
      dysphonia (> 4 months) fitted the acceptance--and exclusion criteria, and
      received functional voice therapy for 2 sessions/week during 3-6 months therapy
      (2x/week). VRP was performed before and after therapy, and a follow-up VRP was
      conducted 3 months after completion of the therapy. RESULTS: The parameters
      "softest intensity" and "VRP--area" seem the most sensitive parameters: they show
      an average highly significant improvement after therapy, and still an average
      significant improvement between the end of treatment and the follow-up
      measurement. CONCLUSION: For daily practice, an index (3 points-index) combining
      Fo-range and softest intensity is proposed.

PMID- 15144024
TI  - [Comparative evaluation of speech disorders and verbal and non verbal
      communication within two groups of patients: patients with facial paralysis (FP)
      and those who had undergone hypoglosso-facial anastomosis (HFA)].
AB  - INTRODUCTION: Speech disorders were often allotted to hypoglossal-facial
      anastomosis (HFA) without being clearly shown. We have compared patients with a
      peripheral facial paralysis at those with HFA. AIMS OF THE STUDY: Retrospective
      study comparing verbal communication (articulation) and non-verbal within two
      groups of patients: patients with patient FP versus with HFA. PATIENTS AND
      METHODS: 10 patients with idiopathic FP versus 7 patients with HFA took part in
      this study. The series of tests includes an evaluation of the motor
      possibilities, bilabial pressure measurement (for the patients with FP), speech
      capacities and finally an evaluation of the verbal and non-verbal communication
      from a scale of satisfaction. RESULTS: The results highlight: the presence of
      real speech disorders (permanent) among patients with FP and their absence among
      patients having profited from HFA; a real satisfaction of the HFA versus FP on
      the quality of life compared to daily tasks, more specifically concerning verbal
      and food skills. CONCLUSION: The HFA is not responsible for speech disorders, and
      makes undeniable improvements confirmed subsequently by the patients.

PMID- 15144025
TI  - Voice prostheses: long-term follow-up retrospective study (three- to sixteen-year
      follow-up of 22 patients).
AB  - BACKGROUND: Thirty-five patients using tracheoesophageal voice with a 3- to 16
      year follow-up were investigated. We analyzed functional voice outcome, voice
      prosthesis (VP) lifespan, and VP-related complications. METHODS: Between 1987 and
      2001, 81 patients underwent total laryngectomy (TL). The 35 currently surviving
      patients (31 men, 4 women) were studied for VP lifespan and VP-related
      complications encountered up to 16 years after surgery. For voice rehabilitation,
      the 35 laryngectomies of our study required 178 prostheses. Short- and long-term
      voice results of 22 patients were compared by objective voice examination:
      maximum phonation time (MPT), intensity range (Int.), fundamental frequency (F0),
      frequency analysis (FA), and voice handicap index (VHI). RESULTS: Long-term
      results are: F0=131 (range: 30-250); Int=22.5 dB (range: 17-35 dB); MPT=4 sec
      (range: 2-12 sec); FA=3 (range: 1-4); VHI=38/120 (range: 8-73). Short- vs long
      term outcome comparison shows the following values: F0: 93 vs 135 Hz; Int: 25 vs
      24 dB; FA: 1 vs 3; and MPT: 21 vs 4 sec. The mean VP lifespan is 165.5 days for
      Provox (range: 2 days-30 months); 143.5 days for Blom-Singer (range: 10 days-24
      months); and 195 days for VoiceMaster (6-7 months). Postoperative complications
      involved 12 cases of periprosthetic leakage (6.74%); 31 granulomas (17.4%); 3
      partial stenoses of the tracheoesophageal tract (1.6%); and 1 temporarily removed
      VP (0.5%). CONCLUSIONS: Complications are generally resolved during standard
      office-setting examination. The commercially available VPs are complementary,
      used according to the diverse characteristics of each VP.

PMID- 15144026
TI  - [Optimizing vocal efficiency by shifting the "laryngeal mechanism"].
AB  - Optimizing vocal efficiency by shifting the "laryngeal mechanism". Some factors,
      either socio-cultural or anatomical, genetic, or habitual, may orient our
      acoustical and phonatory expectations toward a specific "laryngeal mechanism"
      (referred to by Roubeau, Castellengo and Henrich). We prefer to keep the
      laryngeal mechanism we are used to even if our cultural environment or personal
      development offers us another one. Our vocal preferences may thus limit the
      modalities of professional exercise that we choose, and may confront us with
      compensatory symptomatology of vocal fatigue. Professional obligations or
      artistic choices may suggest to the consulting therapist a different orientation
      with respect to laryngeal mechanism whereby functional comfort and acoustical
      efficiency of ambitious vocal performances are optimized. We illustrate this with
      some clinical observations.

PMID- 15144027
TI  - [Vocalab: a new software for voice evaluation and therapy].
AB  - When handling vocal pathologies, speech therapists need tools to visualise voice
      and speech, in order to correlate personal auditory analysis with accurate data.
      Vocalab2 is a spectral analysis tool designed for speech therapists, developed in
      partnership with INSA Toulouse, France. Vocalab is a simple and user-friendly
      tool with important features to be used during evaluation and therapy. The
      software is based on a set of phoniatric data and sophisticated real-time signal
      analysis (Fourier transform, fundamental detection). One of the key tools of
      Vocalab2 is the real-time spectrum for visualising, differentiating and comparing
      every cord approximation and speech movement. Animations are proposed for
      illustrating most phonemes, and videos related to folding cords in the case of
      pathologic and normal sound production are also proposed. An extensive test has
      been conducted during 18 month, with important feedback that has considerably
      improved the tool. The satisfaction ratio is around 8/10.

PMID- 15144028
TI  - [A retrospective study of 91 injections of botulinus toxin into the upper
      sphincter of the oesophagus].
AB  - OBJECTIVE: To evaluate the results of botulinus toxin in dysphagia arising in the
      upper sphincter of the oesophagus. MATERIALS AND METHODS: Since June 1995, 64
      patients have had botulinus toxin injected into the upper sphincter of the
      oesophagus for major swallowing disorders. All cases were treated in the
      dysphagia service, and underwent clinical assessment, video-swallow screening,
      and swallowing therapy. The patient cohort included various pathological groups-
      neurological (vascular accident, head injury, cranial nerve disorders,
      degenerative diseases), postoperative (surgery for carcinoma of the laryngo
      pharynx), and functional, whether purely idiopathic or attributable. RESULTS AND
      CONCLUSIONS: Global analysis of the results shows that botulinus toxin has good
      efficacy in relaxing the upper sphincter of the oesophagus; this does not always
      lead to recovery of normal swallowing, but can bring about improvement by
      assisting in the therapeutic management of the swallowing problem, and in
      improving the dietary intake.

PMID- 15144029
TI  - [Zenker's diverticulum in the elderly patient: evolution of endoscopic treatment
      using a CO2 laser].
AB  - OBJECTIVES: The authors report their experience in a retrospective study of 28
      patients with symptomatic hypopharyngeal diverticulum. MATERIAL AND METHOD: The
      mean age was 70 years. Eight patients presented with severe dysphagia and nine
      with weight's loss. The delay before diagnosis was 17 months. All patients
      included were studied by an oesophageal barium swallow prior to any treatment.
      According to Van Overbeeck's classification, diverticula were medium sized in 11
      patients, small in 8 and large in 7. All patients had endoscopic assessment of
      the diverticular pouch; 26 patients were treated by microendoscopic laser myotomy
      and 2 by resection. RESULTS: The average time for oral feeding was 4 days. None
      of the 28 cases had a postoperative complication. 25 patients had partial or
      complete relief of symptoms after their initial treatment. In 3 cases recurrence
      of symptoms occurred, of whom 2 underwent endoscopic revision and 1 underwent an
      open procedure. CONCLUSION: Endoscopic laser surgery for Zenker's diverticulum
      can be recommended as the treatment of choice for elderly patients. It is a
      useful procedure because it is swift, effective with a low rate of morbidity,
      even in cases with impaired of health or associated diseases.

PMID- 15144030
TI  - [Evaluation and treatment of swallowing disorders after tracheal intubation and
      tracheotomy].
AB  - Swallowing and respiration are well-coordinated and interdependent functions.
      When one of these processes is impaired, the consequence may be negative for the
      other. This article describes the mechanisms of the disorders of swallowing, the
      effects of tracheotomy or intubation and mechanical ventilation on swallowing,
      and the procedures used to assess and treat perturbation of swallowing. Combining
      a basic understanding of these concepts with practical management can increase
      safe and efficient oral intake in patients after artificial ventilation.

PMID- 15144031
TI  - [Dysphagia, a geriatric point of view].
AB  - Dysphagia is most common in geriatric medicine. Aspirations may cause chronic
      inflammatory syndrome or acute pneumonia or heart failure. At-risk patients
      should be recognised: some risks are caused by an acute condition, some by
      chronic disease or handicap. Alzheimer's disease is the most common at-risk
      condition; it is causes a loss of the conscious part of mastication and early
      swallowing. Psychiatric disorders with anorexia should not be overlooked as a
      cause for dysphagia and malnutrition. Due to a longer life, elderly people are
      more likely to have multiple causes for dysphagia. Management of dysphagia in
      geriatric patients is sometimes curative but more often readaptative and
      palliative. It is not restricted to the time of the meals. It first starts with
      avoiding decubitus and maintaining a walking ability. Proper positioning in seats
      and bed involves an occupational therapist. The nutritionist selects tasty and
      appealing meals for each patient. Nurses detect acute confusion as opposed to, or
      in, dementia. The speech therapist takes charge in tutoring the staff in knowing
      what is the secure way to manage an assisted meal, and helps finding the best
      fitted texture for food and drink. Sometimes a proper rehabilitation will be
      feasible. Per endoscopic gastrostomies are mostly restricted to neuro-vascular
      patients and need discussed for their benefit/risk balance. The holistic approach
      needed to manage dysphagia in polypathology elderly patients calls for a
      "cultural" approach of the whole gerontologic team, never the less, accurate
      specialised diagnosis in mandatory.

PMID- 15144032
TI  - Use of a laryngeal mask during medialization laryngoplasty.
AB  - OBJECTIVES: In certain instances medialization thyroplasty under local anesthesia
      is awkward for the patient and complicates surgery. Moreover, for certain
      operations such as for sulcus vergeture or presbyphonia, subjective auditory
      appreciation of vocal improvement under operating room conditions is not
      efficient. In those various instances, we therefore perform thyroplasty under
      general anaesthesia using a laryngeal mask, and under fibrerscopic control.
      MATERIAL AND METHOD: A joint connecting the laryngeal mask to the ventilation
      tube is angled and comprises a small valve through which a fiberscope is slipped.
      We have used this method since April 99 for 11 surgery procedures. RESULTS AND
      CONCLUSION: To date, we have not encountered intraoperative complications that
      have required intubating the patient in order to continue surgery. It can,
      however, occur that a change in head posture during surgery displaces the mask.
      In that event, surgery must be momentarily interrupted in order to re-position
      the mask. The vocal results met expectations.

PMID- 15144033
TI  - ["Sonorous man"--an approach to the singing voice through the process of
      Psychophony].
AB  - Dealing with the voice requires total management, not only of the voice itself,
      but also of the bodily and psychological status. In fact, the patient who
      presents with vocal cord pathology is usually unaware of what has caused abuse of
      his voice. It is therefore our task to restore comfort, but also well-being. Here
      we cover the way in which we intend to guide him towards a new way of voice
      behaviour so that he now concentrates not only on the acoustic qualities of the
      sound he makes, but also on the quality of resonance as well as of posture and
      movement. To achieve this, we must embark on areas often related to play and to
      rich mental imagery in order to support his efforts. The patient or pupil must
      refine his perception of vibration and touch in order to enhance his
      proprioceptive skills.

PMID- 15144034
TI  - [Evaluation of vocal abuse by the patient and correlation with vocal cords
      lesions].
AB  - OBJECTIVE: The aim of this study was to evaluate the recognition by the patient
      of quantitative vocal abuse and its assessment. MATERIALS AND METHODS: 336 files
      of patients presenting with dysphonia were evaluated with a questionnaire
      composed of 4 items. We compared the patients, evaluation of their vocal abuse
      with the presence or absence of benign lesions on the vocal cords. RESULTS AND
      CONCLUSION: Abuse and misuse are often confused and the word abuse does not seem
      to be the most appropriate to describe the quantitative excess of voice use which
      is distinct from misuse.

PMID- 15144035
TI  - [Paracalcitiol compared with calcitriol in treatment of secondary
      hyperparathyroidism in patients with hemodyalisis. Are they really different?].

PMID- 15144036
TI  - [Predictors of colectomy in patients with ulcerative colitis. A cohort analysis
      of 184 cases].
AB  - BACKGROUND: At the present time procto-colectomy is the only potentially curative
      therapeutic measure for patients with ulcerative colitis (UC). Due to its
      morbidity and mortality, several prognostic indexes have been proposed to
      identify subjects in whom surgery could be beneficial. However, they have limited
      availability or they are very cumbersome for the individual patient. AIM: To
      analyze demographic, clinical and biochemical variables in a group of 184 Mexican
      patients with UC in order to identify predicting factors for procto-colectomy.
      PATIENTS AND METHODS: Subjects were divided into two groups: A. Those in whom a
      procto-colectomy was performed (n = 52) and B. Patients on medical treatment in =
      132). Continuous variables were analyzed by means of the Student's t test and
      categorical variables by means of chi-square statistic. A multivariate analysis
      was performed using logistic regression. RESULTS: The main indication for surgery
      was failure to medical treatment (78%). Procto-colectomy was elective in 28 cases
      and an emergency procedure in 14 (7 failures to medical treatment, 4 colonic
      perforations, 2 toxic megacolons and 1 uncontrolled hemorrhage). All operated
      subjects had pancolitis and showed more bloody bowel movements per day (> 10),
      fever (> 38.5 degrees C), tachycardia, hipoalbuminemia and hospitalizations. Only
      hypoalbuminemia in subjects with universal colitis was consistently associated to
      procto-colectomy. CONCLUSION: Pancolitis, hypoalbuminemia and previous
      hospitalizations were the strongest predictors of procto-colectomy in our cohort.
      Thus, serum protein determinations can be useful in patients with universal UC to
      decide surgical therapy.

PMID- 15144037
TI  - Influenza vaccination of patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the safety, the immunogenicity, and the increase of pre
      existing autoantibodies in patients with systemic lupus erythematosus (SLE)
      following influenza vaccination. PATIENTS AND METHODS: Eighteen women with SLE
      received an inactivated influenza vaccine. Antibody titers were measured before
      and 4 weeks after vaccination using a standardized hemagglutination inhibition
      (HAI) assay. Disease activity and antinuclear autoantibodies were determined at
      study entry, at 4 weeks, and at 8 weeks after vaccination. RESULTS: After
      vaccination, the percentage of patients with anti-hemagglutinin antibody levels
      increased significantly but was lower than in healthy women. Mean antibody titer
      of patients increased significantly but also was lower than that of controls.
      Both the mean of disease activity and anti-ds DNA antibody decreased
      significantly. Adverse effects to the vaccine were mild. CONCLUSIONS: a)
      Influenza vaccination appears to be safe; b). Antibody response to influenza
      vaccination increases significantly for all 3 influenza antigens; c) Specific
      antibody response is not significantly affected by treatment, age, IgG levels, or
      disease activity.

PMID- 15144038
TI  - [Fecal incontinence in the elderly].
AB  - Fecal incontinence (FI) is a devastating condition that affects quality of life.
      Age and gender are related with the prevalence of FI. In adults, prevalence
      varies from 2% to 7%. It is more frequent in women than in men (3:1) and is more
      prevalent in elderly patients. There are no studies in Mexico that evaluate the
      frequency of FI in adults older than 60 years. AIM: To investigate the FI
      frequency, severity and associated factors in patients > or = 60 years. PATIENTS
      AND METHODS: Three groups of patients were included: a) Group I: consecutive
      outpatients patients from the Gastroenterology and Geriatrics Clinics of the
      INCMNSZ; b) Group II: INCMNSZ inpatients admitted due to a non-related condition
      with FI; c) Group III: Reyna Sofia nursing home residents (NHR) in Mexico City. A
      structured questionnaire was used to obtain demographic data, comorbidity and
      associated factors with FI. Grade of FI was assessed with the Wexner scale.
      RESULTS: 159 patients were included, 89 (56%) were women. Mean age was 75 years
      (range 59-98). There were 54 patients in group I, 50 in group II and 55 in group
      III. Overall frequency of FI was 33% (n = 53). Frequency of FI was 26% in group
      1, 20% in group II and 53% in group III. Sixty six percent (n = 35) of the FI
      cases were female. Neuropsychiatric disorders were associated to FI in 29
      patients (54%) and diabetes mellitus in 17 (32%). Eighty percent of patients wore
      disposable pads for FI. Urinary incontinence was associated to FI in 31 (58%).
      Thirteen (24%) patients had mild FI, 20 (38%) moderate, and 20 (38%) severe FI.
      The severity score for FI was lower in groups I and II (8.1 y 9.7) than in group
      III (18, p = 0.001). Age in patients with mild FI was significantly lower (73
      years) than in patients with severe FI (83y, p = 0.01). CONCLUSIONS: FI in
      patients older than 60 years old is a very common condition. FI was more frequent
      and severe in women, in NHR and in those with neuropsychiatric disorders. Urinary
      incontinence was associated in half of patients with FI.

PMID- 15144039
TI  - [Reactogenicity of the simultaneous administration of influenza and pneumococcal
      vaccines in adults over 55 years of age].
AB  - BACKGROUND: Pneumonia is the principal cause of morbidity and mortality in PEMEX
      medical services. Vaccination against influenza is 72% effective in preventing
      hospitalizations and 87% effective in preventing deaths related to this virus,
      and vaccination against pneumococcus is 60% effective in preventing invasive
      diseases by this microorganism. ACIP recommends use of both vaccines
      simultaneously in adults over 65 years of age. OBJECTIVES: To describe the
      frequency, duration and severity of local and systemic reactions related to the
      simultaneous administration of vaccines against influenza and pneumococcus in
      adults over 55 years of age, and compare with reactions related to influenza
      vaccine. MATERIAL AND METHODS: Two hundred-thirty two adults over 55 years of age
      were randomly assigned to two groups, group A (114 subjects) received influenza
      vaccine, group B (118 subjects) received influenza and pneumococcus vaccines
      simultaneously. RESULTS: Comparing the number of subjects with local reactions on
      the right arm between groups A and B (17 subjects vs. 27 subjects), differences
      were not statistically significative (p = 0.121). Systemic reactions were not
      statistically significative either (p = 0.126) when results were compared between
      both groups (30 from group A vs. 42 for group B). CONCLUSIONS: Simultaneous
      administration of influenza and pneumococcus vaccines has proven to be safety. In
      the absence of contraindications, there is no reason for not offering both
      vaccines in the same medical visit.

PMID- 15144040
TI  - Pharmacokinetics of digoxin in children with congestive heart failure aggravated
      by other diseases.
AB  - OBJECTIVE: To determine individual digoxin level variations and the effect of
      some common diseases those aggravate congestive heart failure (CHF) on digoxin
      pharmacokinetics in children. DESIGN: Digoxin pharmacokinetics was evaluated in
      11 children with CHF and an additional disease, such as rheumatic fever, anemia
      or infections. Digoxin plasma levels were monitored in patients on multiple-dose
      regime. Setting. Third level pediatric hospital. RESULTS: Pharmacokinetic
      parameters showed extensive variation; median values were: elimination half-life
      42.0 hrs (8.3-77.0), volume of distribution 1.01 L/kg (0.654-6.25), and clearance
      15.0 mL/kg/h (6.0-331.8), which differed from results in patients with only CHF,
      reported previously. Dosage schemes in use at the Cardiology Service produced the
      following results: 40.5% of patients reached therapeutic levels, 10.8% toxic
      levels and 48.6% subtherapeutic levels. CONCLUSION: The range of dosage required
      in order to adjust individual treatments was very wide, leading us to the
      conclusion that therapeutic schemes for this population should be individualized
      based on their pharmacokinetic parameters, and therapeutic monitoring of drugs
      should be performed.

PMID- 15144041
TI  - [Retrospective transfusional audit at the Centro Nacional de la Transfusion
      Sanguinea].
AB  - BACKGROUND: Prior to a blood transfusion, we should consider the risk benefit
      ratio. The literature shows that 18 to 57% of red blood cells, up to 96% of fresh
      frozen plasma and 26% of platelet concentrates are unnecessarily transfused. The
      goal of the present work is to know the appropriateness of transfusion at public
      and private health institutions supported by the Centro Nacional de la
      Transfusion Sanguinea. MATERIAL AND METHODS: An observational, retrospective,
      transverse and descriptive study was carried out by analyzing the requirements of
      blood products considering the patient's diagnosis, requested blood components,
      complete blood count, prothrombin and activated partial thromboplastin time. The
      therapeutic indication was considered either adequate or inadequate according to
      the guidelines for the transfusion therapy of blood products. Descriptive
      statistics for the analysis of the data were used. RESULTS: We analyzed 1,573
      request forms received in year 2001. In 849 cases (55%) the indication was
      adequate, whereas in 724 (45%) the indication of the blood products was
      inadequate. CONCLUSIONS: Our results show that overtransfusion is a common
      practice. We propose to follow the guidelines already established for the
      transfusion of blood components in order to avoid iatrogenia due to
      overtransfusion.

PMID- 15144042
TI  - Production of recombinant rat hepatic histidase.
AB  - Rat liver histidase was expressed in E. coli by using a PCR product of the coding
      sequence obtained from the rat liver cDNA of histidase cloned in the expression
      vector pRSET. The construct (pRSET-HAL) produced a fusion protein containing a
      tail of polyhistidine. The expression product was purified with a resin
      containing Ni+ that retains proteins with polyhistidine fragments. pRSET-HAL was
      analyzed by restriction enzyme mapping and by sequencing confirming the correct
      orientation and nucleotide sequence. Native rat liver histidase was also purified
      and it had a Mr of 72 kDa. An antiserum against native histidase was obtained in
      rabbit. Western blot analysis revealed one band of 72 kDa observed in membranes
      containing purified histidase or rat liver high speed supernatants. The same
      antiserum also detected in cell lysates of E. coli transformed with the pRSET-HAL
      plasmid a single band of 74 kDa of the recombinant histidase before cleavage with
      enterokinase. After the proteolysis, the Western blot analysis showed a single
      band of approximately 72 kDa. Kinetic analysis of the recombinant histidase
      showed similar Km and Vmax compared with native histidase.

PMID- 15144044
TI  - [DNA methylation: an epigenetic process of medical importance].
AB  - Methylation of CpG dinucleotides is an epigenetic mechanism involved in the
      regulation of gene expression in mammals. The patterns of CpG methylation are
      specie and tissue specific. The biological machinery of this system comprises a
      variety of regulatory proteins including DNA methyltransferases, putative
      demethylases, methyl-CpG binding proteins, histones modifying enzymes and
      chromatin remodeling complexes. DNA methylation maintains gene silencing and
      participates in normal development, genomic imprinting and X chromosome
      inactivation. In contrast, alterations in DNA methylation participate in the
      induction of some human diseases, especially those involving developmental
      defects and tumorigenesis. This review summarizes the molecular aspects of DNA
      methylation and its implications in cancer and other human diseases in which this
      epigenetic mechanism has been involved. Our understanding of the epigenetic
      changes that occur in human diseases will be very important for future
      management. Changes in the patterns of methylation can be used as markers in
      cancer and their potentially reversible state creates a target for therapeutic
      strategies involving specific gene re-activation or re-silencing.

PMID- 15144043
TI  - [Treatment of mucormycosis with adjunctive hyperbaric oxygen: five cases treated
      at the same institution and review of the literature].
AB  - INTRODUCTION: Mucormycosis is an invasive fungal infection that affects
      decompensated diabetics, immunosupressed patients and occasionally healthy
      individuals. Despite advances in anti-fungal therapy and surgical techniques, the
      morbidity and mortality remain high. Adjuvant hyperbaric oxygen therapy (HBO) has
      been proposed based on pathophysiology and several favorable clinical reports.
      MATERIAL AND METHODS: A chart review of mucormycosis patients referred to the HBO
      service was performed. Also an electronic search in Medline of relevant
      literature was undertaken. RESULTS: Five mucormycosis patients referred for HBO
      had complete charts available. Four had craniofacial involvement and one had left
      upper extremity involvement. The predisposing diseases were leukemia (n = 3),
      diabetes mellitus plus sarcoidosis (n = 1), and trauma (n = 1). All patients were
      managed with amphotericin B, surgical debridement and HBO. Survival was 60% (3/5)
      three months after the diagnosis was established. The literature was scarce but
      favors HBO. CONCLUSION: Considering the pathophysiology of mucormycosis adjuvant
      HBO therapy seems reasonable. However, the clinical experience is still too
      limited to make HBO part of the standard of care. Prospective, randomized,
      controlled trials will help to define the role of HBO in this devastating
      infection.

PMID- 15144045
TI  - [An update on non-alcoholic fatty liver disease].
AB  - Non alcoholic fatty liver disease is a disease of emerging identity and
      importance. It is frequently associated with obesity, especially visceral fat,
      and is intimately related to fatty liver and markers of insulin resistance. Both
      the prevalence and the severity of liver steatosis are related to body mass
      index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired
      glucose tolerance or type 2 diabetes. The identification fatty liver disease in
      obese patients, is very important in order to prevent complications such as
      steathohepatitis and cirrhosis. The pathogenesis of non alcoholic fatty liver
      disease is very complex, there are mitochondrial morphologic and functional
      alterations, as well as, high sensitivity to injurious stimulus, an increased
      inflammatory activity, and modifications in cellular metabolism at post-receptor
      level. Weight reduction is one of the first steps in the treatment of patients
      with non alcoholic fatty liver disease, as well as the management of associated
      conditions such as obesity, diabetes mellitus and hyperlipidaemia. Antioxidants,
      and others drugs such as ursodeoxycholic acid may be beneficial in the treatment
      of non alcoholic fatty liver disease. These medications, however, need first to
      be tested in well-controlled trials with clinically relevant end-points and
      extended follow-up. In this review, we analyze the new concepts in epidemiology,
      pathophysiology and treatment of this disease.

PMID- 15144046
TI  - [Regulation of NF-kappaB transcription factor. A molecular mediator in
      inflammatory process].

PMID- 15144047
TI  - [Intrauterine infection and preterm birth].

PMID- 15144048
TI  - [Sticky platelet syndrome].

PMID- 15144049
TI  - [Commentaries on the article "Current concepts on surgical management of breast
      cancer"].

PMID- 15144051
TI  - Dating algal origin using molecular clock methods.

PMID- 15144050
TI  - A brief history of plastids and their hosts.

PMID- 15144052
TI  - Plastid functions in the Apicomplexa.

PMID- 15144053
TI  - Origin and fate of chloroplasts in the Euglenoida.

PMID- 15144054
TI  - Protist diversity is different?

PMID- 15144055
TI  - The chloroplast genome of dinoflagellates--a reduced instruction set?

PMID- 15144056
TI  - Mitosis in Giardia lamblia: multiple modes of cytokinesis.
AB  - Mitosis in Giardia is poorly understood. Until today, it is still controversial
      whether Giardia divides with a mirror-image symmetry (ventral-ventral or dorsal
      dorsal) or in a dorsal-ventral mode. Here, we report the different modes by which
      cytokinesis takes place in Giardia lamblia. To determine how Giardia divides,
      video microscopy, scanning electron microscopy, semi-thick sections and freeze
      fracture replicas were analyzed by transmission electron microscopy. Between 12
      and 15% of the cells cultivated for 24-48 h were found in the process of
      division. Three types of cytokinesis were found: (1) ventral-ventral, where the
      discs face each other; (2) dorsal-dorsal, where the discs are in opposite
      directions; and (3) ventral-dorsal. Giardia divides with mirror-image symmetry
      either in ventral-ventral or dorsal-dorsal modes. During ventral-ventral type of
      division, Giardia becomes detached and swims freely in the culture medium,
      whereas, in the other modes of division, the cells can be found either adhered or
      swimming.

PMID- 15144057
TI  - Modeling senescence in hypotrichous ciliates.
AB  - A sexually reproducing hypotrichous ciliates undergo senescence which is in
      general attributed to degenerative processes in the macronucleus, assuming that
      loss of viability is based on loss of genetic elements. It is generally accepted
      that the genetic elements in the macronucleus of hypotrichs segregate randomly, a
      process which potentially can lead to aneuploid imbalances in the distribution of
      gene copies. It is, however, unclear whether there are mechanisms which
      compensate for such imbalances such that each genetic element regains its
      predetermined copy number (regulatory model, conserving euploidy), or whether the
      genetic elements only double, so that genetic imbalances can be inherited to
      further generations (stochastic model, allowing aneuploidy). By means of
      mathematical modeling and simulations, we investigate these two models with
      respect to the number of generations a lineage of hypotrichs can survive under
      asexual conditions. Whereas the regulatory model cannot explain senescence in
      hypotrichs, the stochastic model provides plausible results which, however,
      strongly depend on the assumed distribution of copy numbers which we investigate
      by means of three examples. For both models, simple prediction formulae for the
      approximate survival time of asexually reproducing ciliates are provided.

PMID- 15144058
TI  - Small-subunit ribosomal RNA gene sequences of Phaeodarea challenge the monophyly
      of Haeckel's Radiolaria.
AB  - In his grand monograph of Radiolaria, Ernst Haeckel originally included
      Phaeodarea together with Acantharea and Polycystinea, all three taxa
      characterized by the presence of a central capsule and the possession of
      axopodia. Cytological and ultrastructural studies, however, questioned the
      monophyly of Radiolaria, suggesting an independent evolutionary origin of the
      three taxa, and the first molecular data on Acantharea and Polycystinea brought
      controversial results. To test further the monophyly of Radiolaria, we sequenced
      the complete small subunit ribosomal RNA gene of three phaeodarians and three
      polycystines. Our analyses reveal that phaeodarians clearly branch among the
      recently described phylum Cercozoa, separately from Acantharea and Polycystinea.
      This result enhances the morphological variability within the phylum Cercozoa,
      which already contains very heterogeneous groups of protists. Our study also
      confirms the common origin of Acantharea and Polycystinea, which form a sister
      group to the Cercozoa, and allows a phylogenetic reinterpretation of the
      morphological features of the three radiolarian groups.

PMID- 15144060
TI  - Complex flagellar motions and swimming patterns of the flagellates Paraphysomonas
      vestita and Pteridomonas danica.
AB  - Most flagellates with hispid flagella, that is, flagella with rigid filamentous
      hairs (mastigonemes), swim in the direction of the flagellar wave propagation
      with an anterior position of the flagellum. Previous analysis was based on planar
      wave propagation showing that the mastigonemes pull fluid along the flagellar
      axis. In the present study, we investigate the flagellar motions and swimming
      patterns for two flagellates with hispid flagella: Paraphysomonas vestita and
      Pteridomonas danica. Studies were carried out using normal and high-speed video
      recording, and particles were added to visualize flow around cells generating
      feeding currents. When swimming or generating flow, P. vestita was able to pull
      fluid normal to, and not just along, the flagellum, implying the use of the
      mastigonemes in an as yet un-described way. When the flagellum made contact with
      food particles, it changed the flagellar waveform so that the particle was fanned
      towards the ingestion area, suggesting mechano-sensitivity of the mastigonemes.
      Pteridomonas danica was capable of more complex swimming than previously
      described for flagellated protists. This was associated with control of the
      flagellar beat as well as an ability to bend the plane of the flagellar waveform.

PMID- 15144059
TI  - Dinoflagellate expressed sequence tag data indicate massive transfer of
      chloroplast genes to the nuclear genome.
AB  - The peridinin-pigmented plastids of dinoflagellates are very poorly understood,
      in part because of the paucity of molecular data available from these
      endosymbiotic organelles. To identify additional gene sequences that would carry
      information about the biology of the peridinin-type dinoflagellate plastid and
      its evolutionary history, an analysis was undertaken of arbitrarily selected
      sequences from cDNA libraries constructed from Lingulodinium polyedrum (1012 non
      redundant sequences) and Amphidinium carterae (2143). Among the two libraries 118
      unique plastid-associated sequences were identified, including 30 (most from A.
      carterae) that are encoded in the plastid genome of the red alga Porphyra. These
      sequences probably represent bona fide nuclear genes, and suggest that there has
      been massive transfer of genes from the plastid to the nuclear genome in
      dinoflagellates. These data support the hypothesis that the peridinin-type
      plastid has a minimal genome, and provide data that contradict the hypothesis
      that there is an unidentified canonical genome in the peridinin-type plastid.
      Sequences were also identified that were probably transferred directly from the
      nuclear genome of the red algal endosymbiont, as well as others that are
      distinctive to the Alveolata. A preliminary report of these data was presented at
      the Botany 2002 meeting in Madison, WI.

PMID- 15144061
TI  - Molecular definition and the ubiquity of species in the genus Naegleria.
AB  - To investigate the variability within species of the genus Naegleria, the
      ITS1,5.8S and ITS2 rDNA were sequenced of several strains of N. lovaniensis and
      its Western Australian variants, N. australiensis, N. fowleri, N. andersoni, N.
      jamiesoni, N. tihangensis, N. pringsheimi, N. pagei, N. gruberi sensu lato and a
      Naegleria lineage that lost a group I intron from the SSUrDNA twintron. As a
      result, it is possible to define a molecular species within the Naegleria genus.
      In addition, one strain of each different allozyme cluster was sequenced to
      investigate whether they belong to described species or should be treated as
      distinct new species. This leads to the proposal of eleven new species. The
      sequencing results from those Naegleria spp. of which several strains are
      available indicate that these species are ubiquitous. The only exception might be
      the species represented by the WA variants. However, there are still many
      Naegleria spp. for which only one strain has been isolated, hence, it is
      important that the search for more isolates should be continued worldwide.

PMID- 15144063
TI  - Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of
      the malaria parasite Plasmodium falciparum.
AB  - All eight enzymes required for de novo heme biosynthesis have been predicted from
      the nuclear genome of the human malaria parasite Plasmodium falciparum. We have
      studied the subcellular localization of three of these using a GFP reporter in
      live transfected parasites. The first enzyme in the pathway delta-aminolevulinic
      acid synthase (ALAS) is targeted to the mitochondrion, but the next two enzymes
      porphobilinogen synthase (PBGS) and hydroxymethylbilane synthase (HMBS) are
      targeted to the plastid. An enzymatically active recombinant version of PBGS from
      P. falciparum was over-expressed and its activity found to be stimulated by Mg2+
      (and enhanced by Mn2+) but not by Zn2+. A hypothetical scheme for the exchange of
      intermediates in heme biosynthesis between the mitochondrion and plastid
      organelle, as well as organelle attachment is discussed.

PMID- 15144064
TI  - Irene Manton FRS 1904-1988.

PMID- 15144062
TI  - Diverse eukaryotes have retained mitochondrial homologues of the bacterial
      division protein FtsZ.
AB  - Mitochondrial fission requires the division of both the inner and outer
      mitochondrial membranes. Dynamin-related proteins operate in division of the
      outer membrane of probably all mitochondria, and also that of chloroplasts-
      organelles that have a bacterial origin like mitochondria. How the inner
      mitochondrial membrane divides is less well established. Homologues of the major
      bacterial division protein, FtsZ, are known to reside inside mitochondria of the
      chromophyte alga Mallomonas, a red alga, and the slime mould Dictyostelium
      discoideum, where these proteins are likely to act in division of the organelle.
      Mitochondrial FtsZ is, however, absent from the genomes of higher eukaryotes
      (animals, fungi, and plants), even though FtsZs are known to be essential for the
      division of probably all chloroplasts. To begin to understand why higher
      eukaryotes have lost mitochondrial FtsZ, we have sampled various diverse protists
      to determine which groups have retained the gene. Database searches and
      degenerate PCR uncovered genes for likely mitochondrial FtsZs from the
      glaucocystophyte Cyanophora paradoxa, the oomycete Phytophthora infestans, two
      haptophyte algae, and two diatoms--one being Thalassiosira pseudonana, the draft
      genome of which is now available. From Thalassiosira we also identified two
      chloroplast FtsZs, one of which appears to be undergoing a C-terminal shortening
      that may be common to many organellar FtsZs. Our data indicate that many protists
      still employ the FtsZ-based ancestral mitochondrial division mechanism, and that
      mitochondrial FtsZ has been lost numerous times in the evolution of eukaryotes.

PMID- 15144066
TI  - Partitioning variances of growth in ultrasound longissimus muscle area measures
      in Angus bulls and heifers.
AB  - The objective of the study was to estimate variance components, heritability, and
      repeatability of ultrasound longissimus muscle area (ULMA) measures. Data
      included 4,653 serial ULMA measures from 882 purebred Angus bulls and heifers.
      Animals were born over a 4-yr period from 1998 to 2001. Each year, bulls and
      heifers were ultrasonically scanned four to eight times, with a 4- to 6-wk
      interval between scans. Initially, data were subdivided by scan session across
      years and were analyzed in a multitrait model (MTM). Data pooled across years and
      scan session were then analyzed using random regression models (RRM) to estimate
      trends in genetic parameter estimates. Additive direct genetic variance increased
      with advancing scan session ranging from 8.67 cm4 at the first scan (mean age =
      35 wk) to a maximum of 19.48 cm4 at the sixth scan (mean age = 56 wk).
      Heritability of ULMA increased from 0.35 at first scan to a maximum of 0.48 at
      the fourth scan (mean age = 50 wk). Additive direct genetic variance and
      heritability values at about 1 yr of age (fifth scan) were 18.24 cm4 and 0.45,
      respectively. Estimates from RRM also showed an increase in sigma(a)2 and h2 with
      age. Trends in sigma(pe)2 estimates, although tending to fluctuate, also
      increased with age. Additive direct genetic variance at 1 yr of age ranged from
      15.8 cm4 to 17.0 cm4 for the different models. Heritability of yearling ULMA
      measures ranged from 0.40 to 0.42 and repeatabilities ranged from 0.80 to 0.84.
      For the range of ages used in the current study, both MTM and RRM showed close to
      maximum heritability values at around 1 yr of age. Therefore, phenotypic
      differences in yearling ULMA between Angus cattle are better indicators of
      genetic differences than earlier measurements. Angus breeders could, therefore,
      use ULMA measures made at around 1 yr of age to select next generation parents.

PMID- 15144065
TI  - A mixed-model approach for the analysis of cDNA microarray gene expression data
      from extreme-performing pigs after infection with Actinobacillus
      pleuropneumoniae.
AB  - We proposed a novel statistical approach for the analysis of cDNA experiments
      based on mixed-model methodology combined with mixtures of distributions. Our
      objective was to detect genes that may be involved in conferring heritable
      differences in susceptibility to common infections in intensive pig production.
      We employed a microarray expression profiling strategy and a mixed-model approach
      to the analysis of the expression data. A cDNA microarray of pig with 6,420
      probes from immune tissues and cells was used to compare gene expression in
      peripheral blood leukocytes of two pigs showing extreme performance in their
      response to infection with Actinobacillus pleuropneumoniae. Principal components
      analyses were used to identify the two most extreme-performing pigs after
      infection (i.e., pigs whose measured responses to infection fell at the
      extremes). Blood samples and expression profiles from 0 to 24 h after infection
      were compared using a bivariate, mixed-model approach, in which the effect gene x
      immunological status interaction was treated as a random effect. Bayesian model
      based clustering via mixtures of normal distributions of the resulting BLUP of
      the random interaction was approached and resulted in a list of 307
      differentially expressed genes, of which 179 were down-regulated in the
      susceptible pig. The majority of the differentially expressed genes were derived
      from a cDNA library of leukocytes of A. pleuropneumoniae-challenged pigs that
      were subtracted against leukocytes before the challenge. These results provide
      evidence that the proposed statistical approach was useful in enhancing the
      knowledge of the mechanisms involved in the genetics of the immune response.

PMID- 15144067
TI  - Evaluation of Dorset, Finnsheep, Romanov, Texel, and Montadale breeds of sheep:
      II. Reproduction of F1 ewes in fall mating seasons.
AB  - Objectives were to estimate effects of sire breed (Dorset, Finnsheep, Romanov,
      Texel, and Montadale), dam breed (Composite III and northwestern whiteface),
      mating season (August, October, and December), ewe age (1, 2, and 3 yr), and
      their interactions on reproductive traits of F1 ewes. A total of 1,799 F1 ewes
      produced 3,849 litters from 4,804 exposures to Suffolk rams during 35-d mating
      seasons over 3 yr. Ewes were weighed at breeding. Conception rate and ewe
      longevity (present or absent at 42 mo of age) were determined. Number born and
      litter birth weight were recorded, and number and weight at weaning and 20 wk of
      age were analyzed separately for dam- and nursery-reared litter mates. Total
      productivity through 3 yr of age for each ewe entering the breeding flock was
      calculated as the sum of 20-wk weights for dam- or nursery-reared lambs.
      Interactions of sire breed x mating season, sire breed x ewe age, and mating
      season x ewe age were generally significant, whereas interactions of sire breed,
      mating season, and ewe age x dam breed were seldom detected. Interactions of sire
      breed x mating season were often due to changes in rank as well as magnitude,
      indicating the importance of matching sire breed to a specific mating season. The
      number born to Dorset-, Texel-, and Montadale-sired ewes was not affected by dam
      breed; however, Finnsheep-sired ewes out of northwestern whiteface dams were more
      prolific than Finnsheep-sired ewes out of Composite III dams, and the opposite
      situation existed for Romanov-sired ewes. Least squares means of sire breeds (P <
      0.001) for total productivity of dam-reared lambs were 98.5, 103.5, 106.9, 124.6,
      and 154.9 kg/ewe entering the breeding flock for Texel, Dorset, Montadale,
      Finnsheep, and Romanov, respectively. Superior reproduction of Romanov-sired ewes
      was due to greater conception rate and prolificacy for each mating season and ewe
      age, as well as greater ewe longevity. Total productivity of F1 ewes by Composite
      III dams (125.6 kg) was greater (P < 0.001) than for ewes born to northwestern
      whiteface dams (109.7 kg), and the effect of mating season increased (P < 0.001)
      from August to October to December. Litter weight at 20 wk of age of 2- and 3-yr
      old ewes was similar but greater (P < 0.001) than for 1-yr-old ewes. Experimental
      results provide comprehensive information about the appropriate use of these
      breeds in crossbreeding systems to meet specific production-marketing objectives.

PMID- 15144068
TI  - A bioeconomic approach to derive economic values for pasture-based sheep genetic
      improvement programs.
AB  - Economic values for a range of different maternal and carcass sheep performance
      traits were derived for hill sheep in the United Kingdom. A bioeconomic model
      that includes estimates of available energy supply and herbage intake for sheep
      from hill and mountain pastures, together with that from improved grassland, has
      provided a base from which to define the economic limitations to genetic
      improvement in harsh environments. The degree to which different farm systems can
      accommodate changes in animal performance as a result of genetic improvement was
      explored. Results showed that genetic improvement in harsh environments is likely
      to be of greater benefit to farms with fewer constraints to improvements in
      production, such as better quality pasture or a higher ratio of improved
      grassland to hill pasture. For farm types in the harshest locations, the economic
      value of improving litter size was only positive within defined production
      limits. Increasing litter size beyond these limits resulted in diminishing
      marginal returns because the costs of additional inputs outweighed the benefits
      of extra returns. Results also showed that relative improvements in maternal
      characteristics are at least as economically important as improvements in lamb
      carcass quality. The effects of variation in market prices on economic values for
      the major costs and returns of the sheep enterprises showed that, in general,
      economic values are robust. The methodology described could be adapted and
      applied to other extensive sheep systems worldwide.

PMID- 15144069
TI  - Maximizing genetic gain over multiple generations with quantitative trait locus
      selection and control of inbreeding.
AB  - Stochastic computer simulation was used to investigate the potential extra
      genetic gains obtained from gene-assisted selection (GAS) by combining 1)
      optimization of genetic contributions for maximizing gain, while restricting the
      rate of inbreeding with 2) optimization of the relative emphasis given to the QTL
      over generations. The genetic model assumed implied a mixed inheritance model in
      which a single quantitative trait locus (i.e., QTL) is segregating together with
      polygenes. When compared with standard GAS (i.e., fixed contributions and equal
      emphasis on the QTL and polygenic EBV), combined optimization of contributions of
      selection candidates and weights on the QTL across generations allowed
      substantial increases in gain at a fixed rate of inbreeding and avoided the
      conflict between short- and long-term responses in GAS schemes. Most of the
      increase of gain was produced by optimization of selection candidates'
      contributions. Optimization of the relative emphasis given to the QTL over
      generations had, however, a greater effect on avoiding the long-term loss usually
      observed in GAS schemes. Optimized contribution schemes led to lower gametic
      phase disequilibrium between the QTL and polygenes and to higher selection
      intensities both on the QTL and polygenes than with standard truncation selection
      with fixed contributions of selection candidates.

PMID- 15144070
TI  - The relationships among body weight, body composition, and intramuscular fat
      content in steers.
AB  - Angus steers of known age (265 +/- 17 d) and parentage were used in a 2-yr study
      (yr 1, n = 40; yr 2, n = 45) to evaluate the relationship between percentage of
      i.m. fat content of the longissimus dorsi at the 12th rib and carcass
      characteristics during growth of nonimplanted steers. Steers were sorted by age
      and EPD of paternal grandsire for marbling into high- and low-marbling groups so
      that steers with varying degrees of genetic potential for marbling were evenly
      distributed across slaughter groups. All steers were fed a 90% concentrate corn
      based diet. Steers were allotted to five slaughter groups targeted to achieve hot
      carcass weights (HCW) of 204, 250, 295, 340, and 386 kg over the course of the
      feeding period. Data were analyzed as a completely random design with a factorial
      arrangement of treatments (year, marbling group, and slaughter group). Marbling
      group did not affect backfat, LM area, yield grade (YG), or marbling score.
      Regression equations were developed to quantify the change in carcass
      characteristics and composition over slaughter groups. Hot carcass weight
      increased in a linear fashion and differed (P < 0.01) among the slaughter groups
      as anticipated by design. Yield grade followed a quadratic upward pattern (P <
      0.01) as HCW increased. Slaughter group affected the degree of marbling linearly
      (P < 0.01). There were no slaughter group x marbling group interactions,
      indicating that no differences occurred in the pattern of marbling attributable
      to paternal grandsire EPD. Carcasses expressed small degrees of marbling at 266
      kg of HCW and obtained a YG of 3.0 at 291 kg of HCW. Fractional growth rates
      decelerated with increasing HCW. Greater advances in marbling relative to total
      carcass fatness occurred at HCW less than 300 kg. Management practices early in
      growth may influence final quality grade if compensatory i.m. fat content
      development does not occur.

PMID- 15144071
TI  - Growth and carcass characteristics of lambs sired by Dorper and Dorset rams.
AB  - Growth and carcass merit of Dorset-(DO) and Dorper-sired (DP) lambs were compared
      over 3 yr in matings with 50% Dorset, 25% Rambouillet, 25% Finnsheep ewes. The DP
      were slightly lighter (P = 0.09) at birth than the DO lambs. In the first year of
      the study, DP lambs produced by AI using imported South African sires were
      heavier than DO lambs when weaned at 60 d of age (21.7 vs. 19.5 kg; P = 0.05). In
      yr 2 and 3, however, offspring of natural-service Dorper sires produced in the
      U.S. did not differ in weaning weight from DO lambs (16.9 vs. 17.8 kg; P = 0.02
      for breed x year interaction). Lamb survival was also affected by breed x year
      interaction (P = 0.04). In 2000 and 2001, with 12 to 16% triplet or larger
      litters, mortality was higher for DP lambs (14.9 vs. 7.7%; P = 0.12). However, in
      2002, with approximately 33% triplet or larger litters and with higher mortality
      levels in all birth types, DP lambs had fewer death losses than did DO lambs
      (23.2 vs. 36.1%; P = 0.11). No differences between DO and DP lambs were observed
      in postweaning gain during summer grazing or in drylot in autumn. At chilled
      carcass weights of approximately 25 kg, DP lambs were somewhat fatter than DO
      lambs, with greater body wall thickness (P < 0.01; 22 vs. 19 mm) and slightly
      greater backfat thickness (P = 0.15; 6.4 vs. 5.5 mm) and yield grades (P = 0.15;
      2.9 vs. 2.6). The DP lambs also had more desirable leg scores (P = 0.01; 11.6 vs.
      10.9) and slightly larger LM area (P = 0.13; 14.1 vs. 13.5 mm2) than did DO
      lambs, confirming acceptable muscling and conformation in carcasses from Dorper
      sired lambs. However, differences were not observed in the percentage of carcass
      weight in the leg or loin, or in the lean:bone ratio in the dissected leg.
      Ultrasonic measurements of backfat thickness and LM area taken in live lambs
      before slaughter were positively associated with direct measures on chilled
      carcasses with correlations of 0.77 for backfat thickness and 0.51 for LM area.

PMID- 15144072
TI  - Changes in plasma ghrelin and growth hormone concentrations in mature Holstein
      cows and three-month-old calves.
AB  - We measured changes in plasma ghrelin and GH concentrations in mature Holstein
      cows and 3-mo-old female Holstein calves fed at scheduled times. Our objective
      was to determine the characteristics of ghrelin secretion in dairy cattle and its
      influence on GH. Animals were fed at 0800 and 1600 for 2 wk before and during
      experiments. Plasma was sampled for 24 h at 2-h intervals in Exp. 1. In mature
      cows, plasma ghrelin concentrations decreased (P < 0.01) just after 0800 but not
      at the 1600 feeding. Ghrelin concentrations were lower (P < 0.01) in calves than
      in mature cows and they did not decrease after feeding in calves. The temporal
      relationship between ghrelin and GH remained unclear. In Exp. 2, plasma was
      sampled 2 h before and after both morning and evening feedings at 20-min
      intervals. Plasma ghrelin concentrations decreased (P < 0.05) 40 min after 0800
      feeding and 60 min after 1600 feeding in mature cows. These results indicate that
      in mature cows, plasma ghrelin concentration decreased after feeding, but this
      decrease was not evident in 3-mo-old calves. Further studies are required to
      define the relationship between plasma ghrelin and GH concentrations.

PMID- 15144073
TI  - Isoleucine requirement for late-finishing (87 to 100 kg) pigs.
AB  - Three pig trials were carried out to determine the true digestible Ile
      requirement for maximal weight gain and minimal plasma urea nitrogen (PUN) of
      late-finishing (87 to 105 kg) pigs. In Exp. 1, an Ile-deficient basal diet was
      developed and confirmed to be markedly deficient in Ile, yet fully efficacious
      when fortified with surfeit Ile. This diet contained corn and dried red blood
      cells (RBC) as Ile sources, and was analyzed to contain 10.5% CP, 0.25% Ile, and
      0.63% lysine; ME was calculated to be 3,475 kcal/kg. True digestibility of Ile in
      the basal diet was 88% based on previous digestibility trials in ileal-cannulated
      pigs and cecectomized roosters. Experiment 2 was a growth trial that involved
      five graded levels of crystalline Ile supplementation (0.02%) to generate five
      dose levels of true digestible Ile (0.25 to 0.33%), Diets 1 through 5,
      respectively. Gain and feed efficiency showed a linear response to incremental
      doses of Ile (P = 0.003 and 0.036, respectively), with an apparent plateau at
      0.31% true digestible Ile. In Exp. 3, a replicated 5 x 5 Latin square, five
      barrows (Square 1) and five gilts (Square 2) were used in five 4-d feeding
      periods, with five levels of true digestible Ile (0.22 to 0.30%). Using feed
      intake as a covariate, a linear decrease in PUN occurred in gilts (8.9, 8.6, 8.0,
      7.0, and 5.5; P = 0.004) and in gilts and barrows combined (9.5, 9.2, 9.2, 8.5,
      and 7.6; P = 0.006) as Ile increased incrementally. The PUN results for barrows
      (10.5, 10.0, 10.2, 9.9, and 9.7) were not affected by dietary Ile (P = 0.417).
      The results of these experiments suggest that the factorial requirement estimate
      of 0.30% true digestible Ile for high-lean, late-finishing pigs suggested by the
      NRC Subcommittee on Swine Nutrition is accurate.

PMID- 15144075
TI  - Long-term effects of dietary organic and inorganic selenium sources and levels on
      reproducing sows and their progeny.
AB  - An experiment evaluated the effects of feeding either a basal non-Se-fortified
      diet, two Se sources (organic or inorganic) each providing 0.15 and 0.30 ppm Se,
      or their combination (each providing 0.15 ppm Se) on gilt growth and sow
      reproductive performance. The experiment was a 2 x 2 + 2 factorial conducted in a
      randomized complete block design in three replicates. One hundred twenty-six
      crossbred gilts were started on one of the six treatment diets at 27.6 kg BW.
      During the grower phase, animals were bled at 30-d intervals with three gilts
      killed per treatment at 115 kg BW for tissue Se analysis. Fifteen gilts per
      treatment were bred at 8 mo of age and were continued on their treatment diets
      for four parities. Sow serum collected within parity was analyzed for Se and
      glutathione peroxidase (GSH-Px) activity. Tissue Se was determined from five 0-d
      old pigs per treatment from fourth-parity sows. Three sows per treatment were
      killed after the fourth parity for tissue Se analysis. Similar treatment
      performance responses occurred from 27 to 115 kg BW. Serum Se (P < 0.01) and GSH
      Px activity (P < 0.05) increased for both Se sources to 0.30 ppm Se during the
      grower and reproductive periods. Serum Se and GSH-Px activity decreased from 70
      to 110 d postcoitum in all treatment groups, but increased at weaning (P < 0.01)
      in the Se-fortified groups. The number of pigs born (total, live) increased (P <
      0.05) with the 0.15 ppm Se level for both Se sources. Tissue and total body Se
      content of 0-d-old pigs increased with Se level (P < 0.01) and also when the
      organic Se source (P < 0.01) was fed to the sow. When sows were fed either Se
      source, pig serum Se (P < 0.01) and GSH-Px activity (P < 0.05) increased at
      weaning. Colostrum and milk Se concentrations increased (P < 0.01) with Se level
      for both Se sources, but were substantially greater (P < 0.01) when sows were fed
      organic Se. The combination of Se sources had sow milk and tissue Se values that
      were similar to those of sows milk and fed 0.15 ppm organic Se. The fourth-parity
      sows had greater tissue Se concentrations when organic Se level was increased (P
      < 0.01), more so than when sows were fed inorganic Se. These results suggest that
      both Se sources resulted in similar sow reproductive performances at 0.15 ppm Se,
      but sows fed the organic Se source had a greater transfer of Se to the neonate,
      colostrum, milk, weaned pig, and sow tissues than sows fed inorganic Se.

PMID- 15144074
TI  - Nucleotides in sow colostrum and milk at different stages of lactation.
AB  - An experiment was conducted with the objective of measuring the concentrations of
      total milk solids (TMS), CP, and 5'monophosphate nucleotides in sow colostrum and
      milk. Twelve multiparous sows (Landrace x Yorkshire x Duroc) were used. Litter
      size was standardized at 11 piglets for all sows at farrowing. Sows were fed an
      18.45% CP corn-soybean meal-based diet throughout lactation. The experimental
      period was the initial 28 d of lactation, with colostrum collected within 12 h of
      farrowing and milk collected on d 3, 7, 14, 21, and 28. Colostrum and milk
      samples were analyzed for TMS, CP, adenosine 5'monophosphate (5'AMP), cytidine
      5'monophosphate (5'CMP), guanosine 5'monophosphate (5'GMP), inosine
      5'monophosphate (5'IMP), and uridine 5'monophosphate (5'UMP). Total milk solids
      decreased (P < 0.05) from 26.7% on d 0 to 23.1% on d 3. The TMS further decreased
      (P < 0.05) to 19.3% on d 7, but remained relatively constant thereafter at 18.2,
      18.8, and 19.2% on d 14, 21, and 28, respectively. The concentration of CP
      decreased from 16.6% in colostrum to 7.7, 6.2, 5.5, 5.7, and 6.3% in milk
      collected on d 3, 7, 14, 21, and 28, respectively (linear and quadratic effect; P
      < 0.05). Concentrations of 5'AMP, 5'CMP, 5'GMP, and 5'IMP increased from d 0 to d
      3 and d 7, and then decreased during the remaining lactation period (quadratic
      effect; P < 0.05). The concentration of 5'UMP decreased from d 0 to 28 of
      lactation (linear and quadratic effects; P < 0.05). In colostrum, 5'UMP
      represented 98% of all 5'monophosphate nucleotides, and in milk, 5'UMP accounted
      for 86 to 90% of all nucleotides, regardless of day of lactation. The results of
      this experiment suggest that the concentrations of TMS and CP in sow mammary
      secretions changed during the first week of lactation, but were constant
      thereafter. Likewise, the concentrations of 5'monophosphate nucleotides changed
      during the initial week postpartum, but during the last 2 wk of a 4-wk lactation
      period, the concentrations were constant.

PMID- 15144076
TI  - Evaluation of various inclusion rates of organic zinc either as polysaccharide or
      proteinate complex on the growth performance, plasma, and excretion of nursery
      pigs.
AB  - Three experiments were conducted to evaluate the effects of feeding dietary
      concentrations of organic Zn as a Zn-polysaccharide (Quali Tech Inc., Chaska, MN)
      or as a Zn-proteinate (Alltech Inc., Nicholasville, KY) on growth performance,
      plasma concentrations, and excretion in nursery pigs compared with pigs fed 2,000
      ppm inorganic Zn as ZnO. Experiments 1 and 2 were growth experiments, and Exp. 3
      was a balance experiment, and they used 306, 98, and 20 crossbred pigs,
      respectively. Initially, pigs averaged 17 d of age and 5.2 kg BW in Exp. 1 and 2,
      and 31 d of age and 11.2 kg BW in Exp. 3. The basal diets for Exp. 1, 2, and 3
      contained 165 ppm supplemental Zn as ZnSO4 (as-fed basis), which was supplied
      from the premix. In Exp. 1, the Phase 1 (d 1 to 14) basal diet was supplemented
      with 0, 125, 250, 375, or 500 ppm Zn as Zn-polysaccharide (as-fed basis) or 2,000
      ppm Zn as ZnO (as-fed basis). All pigs were then fed the same Phase 2 (d 15 to
      28) and Phase 3 (d 29 to 42) diets. In Exp. 2, both the Phase 1 and 2 basal diets
      were supplemented with 0, 50, 100, 200, 400, or 800 ppm Zn as Zn-proteinate (as
      fed basis) or 2,000 ppm Zn as ZnO (as-fed basis). For the 28-d Exp. 3, the Phase
      2 basal diet was supplemented with 0, 200, or 400 ppm Zn as Zn-proteinate, or
      2,000 ppm Zn as ZnO (as-fed basis). All diets were fed in meal form. In Exp. 1,
      2, and 3, pigs were bled on d 14, 28, or 27, respectively, to determine plasma Zn
      and Cu concentrations. For all three experiments, there were no overall treatment
      differences in ADG, ADFI, or G:F (P = 0.15, 0.22, and 0.45, respectively).
      However, during wk 1 of Exp. 1, pigs fed 2,000 ppm Zn as ZnO had greater (P < or
      = 0.05) ADG and G:F than pigs fed the basal diet. In all experiments, pigs fed a
      diet containing 2,000 ppm Zn as ZnO had higher plasma Zn concentrations (P <
      0.10) than pigs fed the basal diet. In Exp. 1 and 3, pigs fed 2,000 ppm Zn as ZnO
      had higher fecal Zn concentrations (P < 0.01) than pigs fed the other dietary Zn
      treatments. In conclusion, organic Zn either as a polysaccharide or a proteinate
      had no effect on growth performance at lower inclusion rates; however, feeding
      lower concentrations of organic Zn greatly decreased the amount of Zn excreted.

PMID- 15144077
TI  - Prediction of nutritive values in grass silages: I. Nutrient digestibility and
      energy concentrations using nutrient compositions and fermentation
      characteristics.
AB  - Grass silages (n = 136) were selected from commercial farms across Northern
      Ireland according to their pH, ammonia nitrogen, DM, and predicted ME
      concentration. Each silage was offered to four sheep as a sole feed at
      maintenance feeding level to determine nutrient digestibility and urinary energy
      output. Dry matter concentration was determined as alcohol-corrected toluene DM
      and was subsequently used as the basis for all nutrient concentrations. The
      objectives were to use these data to examine relationships between nutritive
      value and nutrient concentration or fermentation characteristics in silages and
      then develop prediction equations for silage nutritive values using stepwise
      multiple regression techniques. The silages had a large range in quality (DM =
      15.5 to 41.3%, ME = 7.7 to 12.9 MJ/kg of DM, pH = 3.5 to 5.5) and a relatively
      even distribution over the range. There was a positive relationship (P < 0.001)
      between silage GE and DE or ME concentration. Digestible OM in total DM (DOMD);
      ME/GE; and digestibility of DM, OM, and GE were positively related (P < 0.05) to
      CP, soluble CP, ether extract, lactic acid concentration, and lactic acid/ total
      VFA, whereas they were negatively related (P < 0.05) to ADF, NDF, lignin,
      individual VFA concentration, pH, and ammonia N/total N. Concentrations of DE and
      ME and digestibility of CP and NDF had similar relationships with those
      variables, although some relationships were not significant. Three sets of
      multiple prediction equations for DE and ME concentration; ME/ GE; DOMD; and
      digestibility of DM, OM, GE, CP, and NDF were therefore developed using three
      sets of predictors. The first set included GE, CP, soluble N/total N, DM, ash,
      NDF, lignin, lactic acid/total VFA, and ammonia N/total N; the second set
      excluded soluble N/ total N and lignin because they are not typically measured;
      the third set further excluded the fermentation data. The R2 values generally
      decreased with exclusion of predictors. The second and third sets of equations,
      except for NDF digestibility, were validated using the mean-square-prediction
      error model and an independent grass silage data set published since 1977 (n = 17
      [DM digestibility] to 28 [DOMD and OM digestibility]). The validation indicated
      that the equations developed in the present experiment could accurately predict
      DE and ME concentrations and DE/GE and ME/GE in grass silages.

PMID- 15144078
TI  - Prediction of nutritive values in grass silages: II. Degradability of nitrogen
      and dry matter using digestibility, chemical composition, and fermentation data.
AB  - One hundred thirty-six perennial rye-grass silages with wide variations in
      quality were evaluated for N and DM degradability in three beef steers offered
      grass silage of medium quality ad libitum. The silages were incubated in the
      rumen of each animal in triplicate for 0, 6, 12, 24, 48, and 72 h, respectively.
      The disappearance rates of N or DM were used to calculate the readily soluble
      fraction ("a" value), potentially degradable fraction ("b" value), and the
      fractional degradation rate of"b" ("c" value). The effective degradability (P) of
      N or DM was then estimated assuming a ruminal outflow rate of 0.02, 0.05, or
      0.08/h (P0.02, P0.05, or P0.08). The objective was to use these data to develop
      prediction equations for N and DM degradability in grass silages. There were
      considerable variations in "a," "b," and "c" values and the P0.02, P0.05, or
      P0.08 of N and DM (e.g., the P0.02 of N ranged from 75.0 to 93.4% and the P0.02
      of DM from 51.5 to 82.5%). The P0.02, P0.05, or P0.08 of N and DM were negatively
      related (P < 0.001) to ADF, NDF, and lignin concentrations but positively related
      (P < 0.001) to protein fractions (CP, soluble CP, and true protein
      concentrations) and digestibility of DM, OM, GE, CP, and NDF and digestible OM in
      the total DM (measured with sheep). The N and DM degradability data were also
      positively related to silage lactic acid concentration, but the relationships
      between DM degradability data and pH, ammonia N/total N, and VFA concentration in
      silages were negative (P < 0.05). Several sets of prediction equations (linear
      and multiple) were thus developed for N and DM degradability using CP or NDF
      concentration, "a" value or digestibility data as primary predictors, together
      with or without other nutrient concentration and silage fermentation variables.
      All these relationships were highly significant (P < 0.001), and each predictor
      had a significant effect on the relationship (P < 0.05). The R2 values in
      multiple regression for N and DM degradability were generally over 0.70 and
      higher than in linear regression equations. Four equations were also developed to
      convert N and DM degradability at a given ruminal outflow rate, predicted using
      the above-mentioned equations, to their counterparts at any ruminal outflow rate
      (0.02 to 0.10/h), respectively.

PMID- 15144079
TI  - Effects of Sapindus saponaria fruits on ruminal fermentation and duodenal
      nitrogen flow of sheep fed a tropical grass diet with and without legume.
AB  - Six adult African-type hair sheep (BW = 40.3 +/- 6.3 kg) fitted with ruminal and
      duodenal cannulas were subjected to four treatments. Sheep were offered basal
      diets at a rate of 80 g of DM/kg of metabolic BW (equivalent to ad libitum
      access) consisting either of a low-quality grass hay (Brachiaria dictyoneura,
      3.7% CP, DM basis) alone or in combination with a forage legume (Cratylia
      argentea, 18.6% CP, DM basis) in a 3:1 ratio (DM basis). In addition, 0 or 8 g of
      DM of Sapindus saponaria fruits (12.0% crude saponins, DM basis) per kilogram of
      metabolic BW was administered intraruminally. Supplementation of C. argentea
      increased intakes of OM (+21%; P < 0.01) and CP (+130%; P < 0.001), as well as
      ruminal fluid ammonia N concentrations (from 2.40 to 8.43 mg/dL; P < 0.001).
      Apparent OM and N digestibilities were not affected by legume addition, but ADF
      digestibility decreased by 10% (P < 0.01). Total ruminal VFA concentration was
      unchanged, but acetate:propionate was lower (P < 0.01) and isobutyrate proportion
      was greater (P < 0.001) with the legume addition. Legume supplementation
      increased duodenal flows of total N (+56%; P < 0.001), nonammonia N (+52%; P <
      0.001), ruminal escape N (+80%; P < 0.001), and microbial N (+28%; P < 0.05).
      Microbial efficiency was not affected by legume addition. Supplementation of S.
      saponaria increased (P < 0.05) dietary OM intake by 14%, but had no effect on CP
      intake and ruminal fluid ammonia concentration or on OM and N digestion.
      Digestibility of ADF was decreased (P < 0.01) by 10% with S. saponaria as was
      acetate:propionate (P < 0.001) and the isobutyrate proportion (P < 0.001).
      Ruminal protozoa counts increased (P < 0.01) by 67% with S. saponaria. Duodenal N
      flows were not significantly affected by S. saponaria supplementation, except for
      microbial N flow (+34%; P < 0.01). Microbial efficiency was greater (P < 0.05) by
      63% with the addition of S. saponaria. Few interactions between legume and S.
      saponaria supplementation were observed. The NDF digestibility was decreased with
      S. saponaria in the grass-alone diet, but not in the legume-supplemented diet
      (interaction; P < 0.05). Interactions were absent in ruminal fermentation
      measures and duodenal N flow, indicating that effects were additive. Results
      suggest that, even when not decreasing ruminal protozoa count, supplementation of
      S. saponaria fruits is a beneficial way to improve ruminal VFA profile, microbial
      efficiency, and duodenal flow of microbial protein in sheep fed tropical grass
      alone or grass-legume diets.

PMID- 15144080
TI  - Preslaughter stress and muscle energy largely determine pork quality at two
      commercial processing plants.
AB  - The objective of the present experiment was to study physiological changes
      elicited in response to stress in the immediate preslaughter period and to link
      them to pork quality characteristics. Crossbred, halothane-free pigs (n = 192)
      were processed in eight groups (24 pigs per group) on various days at one of two
      commercial processing plants operating different stunning systems (electrical and
      CO2 stunning in Plants A and B, respectively). In each group, half the pigs were
      exposed to either minimal or high preslaughter stress. Blood samples were taken
      at exsanguination, and lactate, cortisol, and catecholamines, as well as blood pH
      and temperature, were assessed and linked to various longissimus muscle quality
      attributes. Additionally, muscle pH and temperature were measured 30 min
      postmortem, and muscle glycolytic potential was determined 22 h postmortem. At
      both processing plants, high preslaughter stress resulted in higher (P < 0.05)
      blood cortisol and lactate; however, the effects of preslaughter stress on
      catecholamines and blood pH were believed to be biased by the different stunning
      methods employed at the plants. High preslaughter stress increased (P < 0.05)
      blood temperature at Plant A but not at Plant B. At both plants, high stress
      increased (P < 0.05) 30-min muscle temperature and decreased (P < 0.05) 30-min
      muscle pH. Ultimate pH was increased (P < 0.05) and muscle glycolytic potential
      was decreased (P < 0.05) by high preslaughter stress. At both plants, high stress
      resulted in inferior pork quality attributes (P < 0.05), including reflectance,
      electrical conductivity, filter paper moisture, drip loss, and L* value. The
      effect of stress was greater on water-holding capacity than on pork color, with
      drip losses increased by 56%. Of all stress indicators measured at
      exsanguination, only blood lactate was strongly correlated with pork quality
      attributes. Regression analyses revealed that blood lactate and glycolytic
      potential accounted for 52 and 48% of the variation in drip loss and L* value,
      respectively. In combination with high preslaughter stress, high glycolytic
      potentials were related to increased drip losses. We conclude that high
      preslaughter stress leads to impaired pork quality, with high muscle energy
      levels aggravating the negative effects of preslaughter stress. Monitoring stress
      level by blood lactate measurement in combination with strategies to control
      muscle energy present at slaughter may help to improve meat quality.

PMID- 15144081
TI  - Feeding 25-hydroxyvitamin D3 to improve beef tenderness.
AB  - The objective of this trial was to determine if a single oral bolus of 25
      hydroxyvitamin D3 (25-OH D3) given at various times before slaughter would
      enhance the tenderness of beef loin steaks. One hundred eight crossbred steers
      were allotted to 18 pens so that the mean weight of the cattle in each pen was
      similar. Treatments (25-OH D3 dose [62.5 or 125 mg]) and time of administration
      of the single oral bolus (4, 7, 21, or 35 d before slaughter) were assigned
      randomly to each pen of steers. Serial plasma samples were collected at each
      bolus administration time for control animals. For steers assigned to a treatment
      group, a baseline blood sample was collected before bolus administration and at
      each subsequent administration when other treatment groups received their bolus.
      Plasma samples were assayed for 25-OH D3 and calcium concentrations. Troponin-T
      degradation and Warner-Bratzler shear force were measured as indicators of
      tenderness for loin steaks collected at slaughter and aged for 6 or 14 d
      postmortem. Muscle samples, collected concurrently, were assayed for 25-OH D3 and
      calcium concentrations. A single oral bolus of 25-OH D3 was sufficient to
      increase plasma 25-OH D3 concentrations (P < 0.001) through slaughter, regardless
      of dose or time of bolus administration. The single oral bolus of 25-OH D3,
      however, did not increase plasma calcium concentrations (P > 0.05). As a result,
      neither troponin-T degradation nor Warner-Bratzler shear force was improved (P >
      0.05) by treatment. Muscle 25-OH D3 concentrations were increased (P > 0.001) by
      treatment with 25-OH D3. Although sustained plasma 25-OH D3 concentrations did
      not increase plasma or muscle calcium at slaughter nor influence tenderness, the
      use of 25-OH D3 as a nutritional means of improving beef tenderness is in its
      infancy, and more research to delineate an effective dose and the potential
      interaction of seasonal exposure to ultraviolet light is warranted.

PMID- 15144082
TI  - Effects of supplemental rumen-protected conjugated linoleic acid or corn oil on
      fatty acid composition of adipose tissues in beef cattle.
AB  - Thirty-six Angus x Hereford heifers (365 +/- 60 kg) were used to determine the
      effects of supplemental dietary lipid sources on fatty acid composition of i.m.,
      perianal (p.a.), and s.c. lipid depots. Lipid was supplied to diets as either
      corn oil or a rumen-protected conjugated linoleic acid (CLA) salt for two
      specific treatment periods of either the final 32 or 60 d on feed. Following an
      initial 56-d feeding period, heifers were fed one of three dietary treatments (DM
      basis): 1) basal diet containing 88% concentrate and 12% grass hay (CON), 2)
      basal diet plus 4% corn oil (OIL), or 3) basal diet plus 2% rumen-protected CLA
      salt (RPCLA) containing 31% CLA. The trans-10, cis-12 CLA concentration was
      greatest (P < 0.05) for heifers fed RPCLA and OIL diets and least (P < 0.05) for
      CON, regardless of time on dietary treatment. Heifers fed supplemental RPCLA had
      greater (P < 0.05) total CLA content than either CON- or OIL-fed heifers. Adipose
      tissue concentration of trans-11 vaccenic acid (TVA) was less (P < 0.05) for CON
      than OIL or RPCLA, which did not differ (P > 0.05). Percentages of C18:1 trans-10
      were least (P < 0.05) in i.m. lipid compared with p.a. and s.c., which did not
      differ (P > 0.05). Following 60 d of lipid supplementation, heifers fed OIL and
      RPCLA had lower (P < 0.05) concentrations of oleic acid and total monounsaturated
      fatty acids (MUFA) compared with CON. The ratio of cis-9, trans-11 CLA:TVA was
      higher (P < 0.05) for heifers fed 60 vs. 32 d, but did not differ (P > 0.05)
      between adipose depots. Feeding OIL increased (P < 0.05) adipose concentration of
      C18:2 fatty acid, whereas feeding RPCLA increased (P < 0.05) total CLA isomers by
      22%. Intramuscular lipid contained the lowest (P < 0.05) percentage of cis-9,
      trans-11 CLA, total CLA, C18:1 cis-9, C18:1 trans-10, and TVA. Total CLA and cis
      9, trans-11 CLA isomers were increased (P < 0.05) in p.a. and s.c. adipose
      depots, whereas i.m. adipose tissue contained increased (P < 0.05) amounts of
      total PUFA. Results from this study indicate that short-term lipid
      supplementation to feedlot cattle can increase adipose tissue CLA concentrations,
      but only marginally (8.3 to 17.5%). Moreover, observed decreases in oleic acid
      and total MUFA concentrations of adipose tissues from heifers fed rumen-protected
      CLA or corn oil suggest that lipid supplementation may decrease delta9 desaturase
      activity in adipose tissues, which in turn would lower the conversion of TVA to
      cis-9, trans-11 CLA isomer.

PMID- 15144083
TI  - Indicators of tenderization are detectable by 12 h postmortem in ovine
      longissimus.
AB  - Postmortem changes in osmotic pressure; ionic strength; pH; temperature; mu- and
      m-calpain; calpastatin; desmin degradation; and myofibril fragmentation index
      (MFI) were determined in ovine longissimus muscle. Our objectives were to
      characterize changes in these variables and to identify postmortem time points at
      which significant proteolysis and tenderization (as measured by change in MFI)
      could be detected. Seven crossbred (Dorset x Romanov) lambs were slaughtered, and
      samples of the longissimus muscle were removed at 0, 3, 6, 9, 12, 24, 72, and 360
      h postmortem. Osmotic pressure increased (P < 0.05) from 379 to 528 mOsm during
      the postmortem storage period, with two-thirds of the increase occurring within
      the first 24 h. By measuring conductivity, we showed that ionic strength
      increased (P < 0.05) from 8.13 to 9.78 mS/cm during the storage period, which is
      equivalent to 79 and 97 mM NaCl solutions, respectively. In accordance with pH
      and temperature, conductivity reached ultimate levels at 24 h postmortem. Within
      9 h postmortem, mu-calpain activity had decreased (P < 0.05) from at-death values
      and continued to decrease until 72 h, at which time it was undetectable. It was
      still possible to detect the 76-kDa isoforms (a product of the autolysis of the
      80-kDa subunit of mu-calpain) immunologically, which implies that the loss of
      activity was not caused by extensive autolysis. In contrast, m-calpain activity
      remained constant throughout the aging period, whereas calpastatin activity was
      stable until 24 h postmortem, after which it gradually decreased. Autolysis
      products of mu-calpain were detected at 3 h postmortem, indicating that mu
      calpain was activated some time between 0 and 3 h postmortem. Moreover, the
      effect of mu-calpain activity on myofibrillar substrates was first observed at 9
      h postmortem, when a 23% loss of native desmin was detected. This degradation
      translated into an increase in MFI at 12 h. Collectively, these results imply
      that mu-calpain is active in postmortem muscle in the presence of calpastatin,
      and that effects of mu-calpain activity as determined by increased MFI are
      detectable during the first 12 h postmortem.

PMID- 15144085
TI  - Light microscopy and image analysis of thin filament lengths utilizing dual
      probes on beef, chicken, and rabbit myofibrils.
AB  - Image analysis procedures for immunofluorescence microscopy were developed to
      measure muscle thin filament lengths of beef, rabbit, and chicken myofibrils.
      Strips of beef cutaneous trunci, rectus abdominis, psoas, and masseter; chicken
      pectoralis; and rabbit psoas muscles were excised 5 to 30 min postmortem.
      Fluorescein phalloidin and rhodamine myosin subfragment-1 (S1) were used to probe
      the myofibril structure. Digital images were recorded with a cooled charge
      coupled device controlled with IPLab Spectrum software (Signal Analytics Corp.)
      on a Macintosh operating system. The camera was attached to an inverted
      microscope, using both the phase-contrast and fluorescence illumination modes.
      Unfixed myofibrils incubated with fluorescein phalloidin showed fluorescence
      primarily at the Z-line and the tips of the thin filaments in the overlap region.
      Images were processed using IPLab and the National Institutes of Health's Image
      software. A region of interest was selected and scaled by a factor of 18.18,
      which enlarged the image from 11 pixels/microm to approximately 200
      pixels/microm. An X-Y plot was exported to Spectrum 1.1 (Academic Software
      Development Group), where the signal was processed with a second derivative
      routine, so a cursor function could be used to measure length. Fixation before
      phalloidin incubation resulted in greatest intensity at the Z lines but a more
      uniform staining over the remainder of the thin filament zone. High-resolution
      image capture and processing showed that thin filament lengths were significantly
      different (P < 0.01) among beef, rabbit, and chicken, with lengths of 1.28 to
      1.32 microm, 1.16 microm, and 1.05 microm, respectively. Measurements using the
      S1 signal confirmed the phalloidin results. Fluorescent probes may be useful to
      study sarcomere structure and help explain species and muscle differences in meat
      texture.

PMID- 15144084
TI  - Characterization of certified Angus beef steaks from the round, loin, and chuck.
AB  - Beef carcasses (n = 150) of A-maturity were selected randomly to determine
      baseline shear force and sensory panel ratings, assess variation in tenderness,
      and evaluate mean value differences between Certified Angus Beef (CAB), commodity
      Choice, and Select steaks. Three steaks were removed from the triceps brachii
      (TB), longissimus lumborum (LL), gluteus medius (GM), semimembranosus (SM),
      biceps femoris (BF), and quadriceps femoris complex (QF), and assigned to Warner
      Bratzler shear (WBSF) and sensory panel analyses. As anticipated, marbling score
      and measured percentage of i.m. fat were greatest (P < 0.05) for CAB,
      intermediate (P < 0.05) for Choice, and least (P < 0.05) for Select carcasses. A
      muscle x quality level interaction (P < 0.05) was observed for WBSF values and
      sensory panel tenderness ratings. The TB, LL, GM, and BF steaks from CAB
      carcasses had lower (P < 0.05) WBSF than Select steaks from the same muscles.
      Even though WBSF values did not differ (P > 0.05) between CAB and Choice QF and
      TB steaks, the LL and GM steaks from CAB carcasses were more tender (P < 0.05)
      than Choice-grade LL and GM steaks. The TB from Select carcasses had higher (P <
      0.05) WBSF values than TB steaks from CAB or Choice carcasses, but sensory panel
      ratings indicated that quality level showed little consistency among the GM, SM,
      BF, and QF. Trained sensory panelists rated CAB LL steaks more tender (P < 0.05)
      than LL steaks from Choice and Select carcasses, and Choice LL steaks were
      evaluated as more (P < 0.05) tender than those from Select carcasses. These
      results demonstrate that the influence of marbling on tenderness was more evident
      in muscles of middle meats than in end cuts, particularly in muscles of the
      round.

PMID- 15144087
TI  - Manipulation of the n-3 polyunsaturated fatty acid content of muscle and adipose
      tissue in lambs.
AB  - Fifty Suffolk-crossbred wether lambs, with an initial live weight of 29 +/- 2.1
      kg, were allocated to one of five concentrate-based diets formulated to have a
      similar fatty acid content (60 g/kg DM), but containing either linseed oil (high
      in 18:3n-3); fish oil (high in 20:5n-3 and 22:6n-3); protected linseed and
      soybean (PLS; high in 18:2n-6 and 18:3n-3); fish oil and marine algae
      (fish/algae; high in 20:5n-3 and 22:6n-3); or PLS and algae (PLS/algae; high in
      18:3n-3 and 22:6n-3). Lambs were slaughtered when they reached 40 kg. Growth
      performance and intake were similar (P > 0.35) among treatments. By contrast,
      gain:feed was higher (P < 0.05) in lambs fed the fish oil compared with the
      linseed oil or PLS/algae diets. Total fatty acid concentration (mg/100 g) in the
      neutral lipid of the longissimus muscle was not affected by treatment (P > 0.87)
      but was least (P < 0.05) in the phospholipid fraction in lambs fed the linseed
      oil diet. Lambs fed either diet containing marine algae contained the highest (P
      < 0.05) percentage of 22:6n-3 in the phospholipid (mean of 5.2%), 2.8-fold higher
      than in sheep fed the fish oil diet. In lambs fed the fish/algae diet, the
      percentage of 20:5n-3 was highest (P < 0.05), contributing some 8.7, 0.8, and
      0.5% of the total fatty acids in the muscle phospholipid, neutral lipids, and
      adipose tissue, respectively. The percentage of 18:3n-3 in the phospholipid
      fraction of the LM was highest (P < 0.05) in lambs fed the linseed oil diet
      (6.9%), a value double that of sheep fed the PLS diet. By contrast, lambs fed the
      PLS diet had twice the percentage of 18:3n-3 in the muscle neutral lipids (3.8%)
      than those offered the linseed oil diet, and 5.5-fold greater than lambs fed the
      fish/algae treatment (P < 0.05), an effect that was similar in the adipose
      tissue. The percentage of 18:2n-6 was highest (P < 0.05) in lambs fed the PLS
      diet, where it contributed 33.7, 10.1, and 11.2% in the muscle phospholipid,
      neutral lipids, and adipose tissue, respectively. The highest (P < 0.05) muscle
      PUFA-to-saturated fatty acid (P:S) ratio was obtained in lambs fed the PLS diet
      (0.57), followed by the PLS/algae diet (0.46), and those fed the fish oil or
      linseed oil diets had the lowest ratios (0.19 and 0.26, respectively). The
      favorable P:S ratio of lambs fed the PLS/algae diet, in conjunction with the
      increased levels of 20:5n-3 and 22:6n-3, enhanced the nutritional qualities of
      lamb to more closely resemble what is recommended for the human diet.

PMID- 15144086
TI  - Timing of magnesium supplementation administered through drinking water to
      improve fresh and stored pork quality.
AB  - Thirty-two pigs were used to determine the timing effect of magnesium (Mg)
      supplementation given through drinking water on pork quality. Pigs (16 barrows
      and 16 gilts) were individually penned, provided 2.7 kg of feed (0.12% Mg) daily
      (as-fed basis), and allowed free access to water via a nipple waterer for the
      duration of the study. After 5 d of adjustment, pigs (120 +/- 0.8 kg BW) were
      allotted randomly by weight and sex to 900 mg/L of supplemental Mg from magnesium
      sulfate heptahydrate in drinking water for -6, -4, -2, or 0 d relative to
      slaughter. The LM and semimembranosus (SM) muscles were removed 24 h postmortem.
      Retail display storage was simulated for 8 d, and the LM was vacuum-packaged for
      25 or 50 d at 4 degrees C. Magnesium did not affect the pH of the LM at either 45
      min (P = 0.15) or 24 h postmortem (P = 0.23). However, the pH of the SM at 24 h
      postmortem tended to be greater (P = 0.08) for pigs consuming Mg for 2 d than for
      those not supplemented. Fluid loss after 8 d of storage was less (P < 0.05) in
      the LM of pigs supplemented with Mg for 6 d than in those without
      supplementation. Furthermore, fluid loss from the SM of pigs provided
      supplemental Mg for 2 d, but not for 4 or 6 d, was lower (P < 0.05) on each day
      of retail display than the SM of unsupplemented pigs. Minolta L*, a*, and b*
      color measurements of the LM during display storage were not (P > 0.10) affected
      by Mg supplementation. However, Mg supplementation for 2 or 4 d decreased
      paleness (lower L* value) after 25 d (P < 0.05), but not 50 d (P > 0.10) of
      vacuum-packaged storage. Magnesium addition for 2 d decreased the extent of
      oxidation (thiobarbituric acid-reactive substances) of the LM after 4 d of
      display storage compared with 0 d of Mg (P < 0.05). Oxidation of the SM during 8
      d of display storage increased linearly (P < 0.05) as duration of supplementation
      increased from 2 to 6 d but did not differ (P = 0.22) from 0 d of Mg
      supplementation. Although the response to Mg supplementation was variable,
      supplementation for 2 d before slaughter was considered most efficacious because
      of the following: decreased fluid loss from the SM, and lower lipid oxidation
      formation in the LM during retail storage; a darker, more desirable LM color
      after 25 d of vacuum-packaged storage; and cost reductions compared with longer
      durations.

PMID- 15144088
TI  - Consumer acceptance of calcium chloride-marinated top loin steaks.
AB  - In this study, a multi-city, retail consumer survey was used to determine whether
      marinating in calcium chloride at 72 h postmortem improves consumer and trained
      sensory panel evaluations of beef loin steaks, Warner-Bratzler shear force (WBSF)
      values, and the value of CaCl2 marinades to improve tenderness in a national
      consumer market. Boneless strip loin subprimals (n = 8) were obtained from eight,
      not electrically stimulated, USDA Standard-grade carcasses, halved, and
      alternating ends were marinated with 200 mM CaCl2 at 5% (wt/wt) or not injected
      (controls). Strip loins were then aged for 7 d in vacuum packages at 2 degrees C
      before WBSF, trained or consumer evaluations. Four trained research teams
      traveled on the same 7-d period to collect the consumer data. Consumers (n = 393;
      minimum of 10 consumers/panel, three panels/store, three stores/city, and four
      cities) varying widely in income level, education, and gender evaluated the
      steaks for tenderness, beef flavor, juiciness, and overall quality in each of
      three supermarkets in major cities (Los Angeles, CA; Baltimore, MD; Chicago, IL;
      and Dallas, TX). The average improvement (P < 0.05) in WBSF for steaks marinated
      with CaCl2 was 1.39 kg. Trained panelists scored marinated steaks higher (P <
      0.05) than control steaks in sustained juiciness (6.00 vs. 5.09), beef flavor
      (6.31 vs. 5.64), and overall mouth-feel (5.98 vs. 4.93). Consumers also rated
      marinated steaks higher (P < 0.05) than control steaks in juiciness (5.98 vs.
      5.45), beef flavor (6.70 vs. 6.05), tenderness (6.75 vs. 5.89), and overall
      quality (6.68 vs. 6.20). Consumers in this study would pay dollar 0.95/kg more
      for steaks marinated with CaCl2, adding dollar 21.64 to the value of a loin from
      tough carcasses. These results indicate that consumers can differentiate
      tenderness levels and are willing to pay a premium for calcium chloride
      marinating to effectively improve the quality of beef loin steaks.

PMID- 15144089
TI  - Bovine metalloprotease characterization and in vitro connective tissue
      degradation.
AB  - Metalloproteases that selectively hydrolyze connective tissue proteins may
      tenderize meat without creating texture problems associated with myofibrillar
      protein degradation. Our objective was to characterize the activity of bovine
      placental proteases to determine whether they can improve meat tenderness through
      disruption of the connective tissue matrix. Enzymes were extracted, crudely
      purified, and proteolytic activity was assessed against gelatin and collagen
      under varying pH and temperature conditions using both SDS-PAGE and zymography.
      Gelatin zymography revealed proteolysis between 57 and 63 kDa, with decreased
      activity as buffer pH decreased from pH 7.4 to 5.4 (37 degrees C). Proteolytic
      activity was pronounced at 37 degrees C, moderate at 25 degrees C, and absent at
      4 degrees C following 48-h incubation (pH 7.4). Placental enzymes were
      metalloproteases inhibited by excess EDTA. Maximum proteolysis was achieved in
      the presence of Ca2+, with or without Mg2+ and Zn2+. Absence of Ca2+ decreased
      proteolytic activity. Complete degradation of both the 125- and 120-kDa proteins
      of the alpha-chains of gelatin was achieved following enzyme incubation for 6 h
      at 37 degrees C or 24 h at 25 degrees C. No degradation was observed following
      enzyme incubation with native Type I collagen. Given the marked decrease in
      enzyme activity at pH 5.4 and 4 degrees C (standard industry conditions), bovine
      placental metalloproteases would not be expected to contribute to connective
      tissue degradation or improve meat tenderness.

PMID- 15144090
TI  - Behavior and reproductive performance by stalled breeding females on a commercial
      swine farm.
AB  - The behavior of stalled females pigs was observed to investigate the relations
      between behavior and reproductive performance. A commercial farrow-to-finish farm
      equipped with a computerized recording system with approximately 300 female pig
      inventories was visited three times to observe three postural behaviors (lying,
      standing, and sitting) and three stereotypies (vacuum chewing, drinker playing,
      and bar biting) of stalled females at 15-min intervals for 6 h (25 times
      including 0 min of one zero-time sampling) after feeding. Relative frequencies
      (%) of the postural behaviors and the stereotypies for 6 h were expressed as a
      percentage of a total of 25 time observations. Statistical models for
      reproductive performance included each behavior, parity, and day of visit. Among
      609 pregnant females observed at our three visits, the means in relative
      frequencies (%) of lying, standing, sitting, vacuum chewing, drinker playing, and
      bar biting for 6 h were 60.1 +/- 0.91, 32.3 +/- 0.87, 7.60 +/- 0.44, 12.7 +/-
      0.65, 0.4 +/- 0.06, and 0.2 +/- 0.50%, respectively. Among 514 farrowed females
      of the 609 pregnant females, the means of total pigs born, pigs born alive, pigs
      born dead, birth litter weights, pigs weaned, and adjusted 21-d litter weights
      were 12.3 +/- 0.13, 11.2 +/- 0.12, 1.1 +/- 0.06, 17.1 +/- 0.18 kg, 10.3 +/- 0.08,
      and 68.1 +/- 0.40 kg, respectively. Females showing a high relative frequency (>
      or = 36%) of vacuum chewing during gestation produced fewer (P < 0.05) total pigs
      born (11.7 +/- 0.38 vs. 12.6 +/- 0.22) than those showing no vacuum chewing. No
      relationships were found between vacuum chewing and other performance
      measurements such as pigs born alive, pigs weaned, and adjusted 21-d litter
      weights. Neither postural behavior nor the other stereotypies were related to
      reproductive performance. The farrowing rate was not related to any postural
      behavior and stereotypy in logistic regression mixed models. This study suggests
      that a subpopulation of females exists on commercial farms that frequently
      exhibit vacuum chewing and give birth to fewer total pigs. High frequency of
      vacuum chewing in those females may be indicative of their suboptimal
      reproductive performance.

PMID- 15144092
TI  - Semen characteristics and libido in boars treated repeatedly with PGF2alpha.
AB  - The objective was to determine the effects of repeated injections of PGF2alpha
      (Lutalyse; Pfizer) on semen and libido characteristics in terminal-line boars.
      Semen was collected once weekly from wk 0 to 15 and on four consecutive days
      during wk 16. Boars received an i.m. injection of 10 mg of PGF2alpha (n = 11) or
      2 mL of vehicle (n = 11) immediately before entering the collection room. For the
      weekly collections, semen volume (220.3 +/- 3.2 mL; mean +/- SE), gel weight
      (38.7 +/- 0.7 g), total sperm cells (65.4 +/- 1.2 billion), motile sperm cells
      (67.4 +/- 0.6 %), and sperm velocity (125.9 +/- 1.2 microm/s), were affected by
      time (P < 0.01) but not by treatment (P > 0.10). Sperm concentration (0.31 +/-
      0.01 billion/mL) was not affected (P > 0.10) by time or treatment. The percentage
      of morphologically normal sperm cells, assessed at wk 16, did not differ (P =
      0.39) between groups (80.8 +/- 1.0). Libido was evaluated from wk 0 to 16. There
      were no effects of treatment or time (P > 0.10) on the period from injection to
      the start of ejaculation (225.6 +/- 9.1 s). Duration of ejaculation was affected
      by treatment (P < 0.01; 472.0 +/- 43.1 s and 280.4 +/- 43.1 s, for PGF2alpha
      treated and control boars, respectively) and time (P < 0.01). During the
      intensive collection period (wk 16), semen volume (200.1 +/- 7.1 mL), gel weight
      (39.2 +/- 1.5 g), sperm concentration (0.19 +/- 0.01 billion/ mL), total sperm
      cells (39.5 +/- 3.6 billion), motile sperm cells (65.6 +/- 2.2%), and sperm
      velocity (117.8 +/- 3.7 microm/ s) were affected by time (P < 0.10) but not by
      treatment (P > 0.10). The period from injection to the start of ejaculation
      tended to decrease (by 44%) during the intensive collection period in PGF2alpha
      treated boars, but not in controls (treatment x time, P = 0.07). Regardless, the
      period from injection to the start of ejaculation did not differ (P = 0.63)
      between groups on d 4 of the intensive collection period. Duration of ejaculation
      was affected by treatment (P < 0.01; 459.1 +/- 24.1 s for PGF22alpha-treated
      boars vs. 303.1 +/- 24.1 s for controls) but not by time (P > 0.10). Overall,
      there were no exceptional positive or negative effects of long-term treatment
      with PGF2alpha on semen characteristics and libido in boars.

PMID- 15144091
TI  - Effect of supranutritional and organically bound selenium on performance, carcass
      characteristics, and selenium distribution in finishing beef steers.
AB  - Dietary selenium influences the Se content in edible muscle of beef cattle.
      Limited data are available to describe the effects that feeds naturally high in
      Se have on production, carcass characteristics, and Se distribution in terminal
      tissues. Therefore, 43 crossbred steers (BW = 351 +/- 24 kg) were stratified by
      BW and assigned to one of four dietary treatments: Se adequate (CON; n = 12), Se
      provided as high-Se wheat (WHT; n = 9), high-Se hay (HAY; n = 11), or sodium
      selenate (SEO; n = 11). Daily selenium intake for WHT, HAY, and SEO diets was 65
      microg/kg BW, whereas it was 9.5 microg/kg BW for CON. Diets were similar in
      ingredient composition (25% wheat, 39% corn, 25% grass hay, 5% desugared
      molasses, and 6% wheat middling-based supplement; DM basis), isonitrogenous and
      isocaloric (14.0% CP, 2.12 Mcal NEm/kg DM and 1.26 Mcal NEg/ kg DM), and offered
      once daily (1500) individually to steers in a Calan gate system for 126 d. At the
      end of the trial, steers were slaughtered; carcass data were recorded; and
      samples of the liver, kidney, spleen, semitendinosus, and hair were collected for
      Se analysis. Intake of DM, G:F, and ADG did not differ (P > 0.13). No differences
      (P > 0.12) were noted for hot carcass weight, organ weights, longissimus muscle
      area, back-fat thickness, marbling scores, or quality and yield grade. Kidney,
      pelvic, and heart fat tended to be higher (P = 0.06) in CON and WHT compared with
      SEO and HAY steers (2.9, 2.4, 2.5, 2.9 +/- 0.2% for CON, SEO, HAY, and WHT,
      respectively). Selenium concentrations in all tissues collected differed (P <
      0.003) due to treatment. Distribution of Se to the kidney, spleen, and hair were
      similar with CON < SEO < HAY < WHT (8.40, 10.05, 10.86, 12.89 +/- 0.26 ppm for
      kidney; 2.00, 2.60, 3.82, 5.16 +/- 0.09 ppm for spleen; 1.80, 4.00, 5.93, 10.54
      +/- 0.56 ppm for hair; P < 0.01). The distribution of Se in liver and muscle (DM
      basis) differed from that in other tissues, with CON < HAY < SEO = WHT (2.33,
      6.56, 9.91, 10.79 +/- 0.80 ppm; P < 0.01) and CON = SEO < HAY < WHT (1.33, 1.55,
      3.32, 4.41 +/- 0.18 ppm; P < 0.01), respectively. When providing dietary Se at
      supranutritional levels, source of Se did not affect production or carcass
      characteristics, but it altered the distribution and concentration of Se
      throughout the tissues of finishing beef steers.

PMID- 15144093
TI  - Increasing weaning age improves pig performance in a multisite production system.
AB  - Two trials were conducted to determine the effects of weaning age on pig
      performance in a multisite production system. The second trial also evaluated the
      effects of modifying the nursery feeding program according to weaning age. In
      Trial 1 (2,272 pigs), treatments included weaning litters at 12, 15, 18, or 21 d
      of age. In Trial 2 (3,456 pigs), litters were weaned at 15, 16, 18, 19, 21, or 22
      d of age and categorized into three treatments (15.5, 18.5, or 21.5 d of age). In
      Trial 2, pigs in each age group were fed one of two nursery feeding programs.
      Nursery feeding programs varied in both diet formulation and in the quantity of
      diets fed containing increased levels of whey and spray-dried animal plasma. Each
      trial was conducted as a randomized complete block design with four blocks of
      nursery and finishing sites. All weaning-age treatments were weaned from a 7,300
      sow farm on the same day into the same nursery. Each block remained intact as
      pigs moved from nursery to finishing site. Increasing weaning age (12, 15, 18, or
      21 d in Trials 1; and 15.5, 18.5, or 21.5 d in Trial 2) increased (linear, P <
      0.001) ADG (299, 368, 409, 474 +/- 7 g/d; 435, 482, 525 +/- 13 g/d) and tended to
      decrease (linear, P < 0.09) mortality (5.25, 2.82, 2.11, 0.54 +/- 0.76%; 2.17,
      1.56, 1.30 +/- 0.36%) in the initial 42 d after weaning. Finishing ADG (722, 728,
      736, 768 +/- 11 g/d; 783, 790, 805 +/- 11 g/d) also improved (linear, P < 0.01)
      with increasing weaning age. Overall, increasing weaning age increased (linear, P
      < 0.001) wean-to-finish ADG (580, 616, 637, 687 +/- 8 g/d; 676, 697, 722 +/- 6
      g/d), weight sold per pig weaned (94.1, 100.5, 104.4, 113.1 +/- 1.3 kg; 107.6,
      111.6, 116.2 +/- 1.1 kg), and decreased (linear, P < 0.03) mortality rate (9.4,
      7.9, 6.8, 3.6 +/- 0.95%; 3.9, 3.4, 2.5 +/- 0.5%). Altering the nursery feeding
      program did not affect wean-to-finish growth performance. In this multisite
      production system, increasing weaning age from 12 to 21.5 d of age increased
      weight sold per pig weaned by 1.80 +/- 0.12 kg for each day increase in weaning
      age. These studies suggest increasing weaning age up to 21.5 d can be an
      effective management strategy to improve wean-to-finish growth performance in
      multisite pig production.

PMID- 15144095
TI  - Daily and alternate-day supplementation of urea or biuret to ruminants consuming
      low-quality forage: II. Effects on site of digestion and microbial efficiency in
      steers.
AB  - Five steers (491 +/- 21 kg BW) were used in an incomplete 5 x 4 Latin square with
      four 24-d periods to determine the influence of supplemental non-protein N (NPN)
      source and supplementation frequency (SF) on nutrient intake and site of
      digestion in steers consuming low-quality grass straw (4% CP). Treatments (TRT)
      included an unsupplemented control and a urea- or biuret-containing supplement
      placed directly into the rumen daily (D) or every other day (2D) at 0700. The NPN
      treatments were formulated to provide 90% of the estimated degradable intake
      protein requirement. Daily TRT were supplemented CP at 0.04% of BW/d, whereas the
      2D TRT were supplemented at 0.08% of BW every other day. Therefore, all
      supplemented TRT received the same quantity of supplemental CP over a 2-d period.
      Forage OM intake was not affected (P > 0.05) by NPN supplementation, NPN source,
      or SF; however, total OM and N intake were increased (P < 0.01) with CP
      supplementation. Duodenal flow of N was greater (P = 0.04) with CP
      supplementation compared with the control. In addition, duodenal bacterial N flow
      was increased with CP supplementation (P = 0.04) and for biuret compared with
      urea (P < 0.01). Bacterial efficiency (g bacterial N/kg OM truly digested in the
      rumen) was greater (P = 0.05) for biuret than for urea. Apparent total-tract N
      digestibility was increased with NPN supplementation (P < 0.01) but not affected
      by NPN source or SF. These results suggest that urea or biuret can be used
      effectively as a supplemental N source by steers consuming low-quality forage.

PMID- 15144094
TI  - Daily and alternate day supplementation of urea or biuret to ruminants consuming
      low-quality forage: I. Effects on cow performance and the efficiency of nitrogen
      use in wethers.
AB  - Two experiments were conducted to determine the influence of supplemental
      nonprotein N (NPN) provided daily (D) or every other day (2D) on ruminant
      performance and N efficiency. Treatments included an unsupplemented control (CON)
      and a urea (28.7% CP) or biuret (28.6% CP) supplement provided D or 2D at 0700.
      In Exp. 1, five wethers (39 +/- 1 kg BW) were used in an incomplete 5 x 4 Latin
      square with four 24-d periods to determine the influence of supplemental NPN
      source and supplementation frequency (SF) on the efficiency of N use in lambs
      consuming low-quality grass straw (4% CP). The amount of CP supplied by each
      supplement was approximately 0.10% of BW/d (averaged over a 2-d period). In Exp.
      2, 80 Angus x Hereford cows (540 +/- 8 kg BW) in the last third of gestation were
      used to determine the effect of NPN source and SF on cow performance. The NPN
      treatments were formulated to provide 90% of the estimated degradable intake
      protein requirement. The supplemented treatments received the same amount of
      supplemental N over a 2-d period; therefore, the 2D treatments received double
      the quantity of supplemental N on their respective supplementation day than the D
      treatments. In Exp. 1, total DM, OM, and N intake; DM, OM, and N digestibility; N
      balance; and digested N retained were greater (P < 0.03) for supplemented than
      for CON wethers, with no difference (P > 0.05) between NPN sources or SF. Plasma
      urea-N (PUN) was increased with N supplementation compared with CON (P < 0.01),
      and urea treatments had greater PUN than biuret (P < 0.01). In addition, PUN was
      greater (P = 0.02) for D than for 2D treatments. In Exp. 2, pre- and postcalving
      (within 14 d and 24 h after calving, respectively) cow weight and body condition
      score change were more positive (P < 0.05) for supplemented groups than for CON.
      These results suggest that supplements containing urea or biuret as the primary
      source of supplemental N can be effectively used by lambs and cows consuming low
      quality forage, even when provided every other day.

PMID- 15144097
TI  - The influence of high-nitrogen forages on the voluntary feed intake of sheep.
AB  - The objective of this research was to examine the effect of high concentrations
      of nonprotein nitrogen (NPN) on the voluntary food intake of sheep fed high
      quality grasses. Wether lambs (n = 6 per treatment) were fed dried switchgrass
      (Panicum virgatum L.; Exp. 1) or dried tall fescue (Festuca arundinacea Schreb.;
      Exp. 2). In both experiments, urea was added to the dried forage at 0 (control),
      12, or 24 g of N/kg of DM to increase the NPN concentration. Acid detergent fiber
      concentrations were 305 g/kg of DM in both experiments, although DM digestibility
      was 663 and 618 g/ kg of DM in Exp. 1 and Exp. 2, respectively. Voluntary feed
      intake of the control forage was 28.2 and 19.1 g/ kg of BW in Exp. 1 and Exp. 2,
      respectively, and decreased for the high-urea treatments to 25.2 and 16.2 g/kg of
      BW in Exp. 1 (P = 0.07) and Exp 2 (P = 0.03), respectively. Total feed N
      concentrations increased from 29.5 g to 45.7 g of N/kg of DM in Exp. 1 (P < 0.01)
      and from 28.4 to 55.9 g of N/kg of DM in Exp. 2 (P < 0.01). Nonprotein N
      concentrations increased from 28.3 to 53.8% of the total N in switchgrass diets
      (Exp. 1; P < 0.01), and from 26.4 to 64.0% in tall fescue diets (Exp. 2; P <
      0.01). Plasma urea concentrations of the lambs increased from 3.1 to 6.6 mM (Exp.
      1; P < 0.01) and from 2.9 to 5.8 mM (Exp. 2; P < 0.01) as the amount of urea
      added to the diets increased. These changes resulted in an increase in plasma
      osmolality from 298 to 307 mOsm/kg (Exp. 1; P = 0.04), and from 299 to 307
      mOsm/kg (Exp. 2; P = 0.06). Increasing feed N and NPN concentrations through the
      addition of urea caused a significant decrease in the voluntary feed intake of
      sheep fed tall fescue and switchgrass. These responses showed no significant
      cause-and-effect relationship between voluntary feed intake, plasma urea
      concentrations, and plasma osmolality.

PMID- 15144096
TI  - Daily and alternate-day supplementation of urea or biuret to ruminants consuming
      low-quality forage: III. Effects on ruminal fermentation characteristics in
      steers.
AB  - Five ruminally and duodenally cannulated steers (491 +/- 21 kg BW) were used in
      an incomplete 5 x 4 Latin square with four 24-d periods to determine the
      influence of supplemental nonprotein N (NPN) source and supplementation frequency
      (SF) on the dynamics of ruminal fermentation in steers consuming low-quality
      grass straw (4% CP). Treatments (TRT) included an unsupplemented control (CON)
      and a urea or biuret supplement that were placed directly into the rumen at 0700
      daily (D) or every other day (2D). The NPN treatments were formulated to provide
      90% of the estimated degradable intake protein requirement; therefore, the urea
      and biuret treatments received the same amount of supplemental N over a 2-d
      period. Daily TRT were supplemented with CP at 0.04% of BW/d, whereas the 2D TRT
      were supplemented at 0.08% of BW every other day. Forage was provided at 120% of
      the previous 5-d average intake in two equal portions at 0715 and 1900. Ruminal
      fluid was collected 0, 3, 6, 9, 12, and 24 h after supplementation on a day of
      and a day before supplementation for all TRT. Ruminal NH3-N increased (P < 0.04)
      with CP supplementation on the day all supplements were provided and on the day
      on which only daily supplements were provided compared with the CON. However, an
      NPN source x SF interaction (P = 0.03) on the day all supplements were provided
      indicated that NH3-N increased at a greater rate for urea as SF decreased
      compared with biuret. Ruminal NH3-N on the day only daily supplements were
      provided was greater (P = 0.02) for D compared with 2D. On the day all
      supplements were provided, D increased (P = 0.05) ruminal indigestible acid
      detergent fiber passage rate and ruminal fluid volume compared with 2D. These
      results suggest that urea or biuret can be used effectively as a supplemental N
      source by steers consuming low-quality forage without adversely affecting ruminal
      fermentation, even when provided every other day.

PMID- 15144098
TI  - A simulation exercise to teach principles of bovine reproductive management.
AB  - Students in Reproductive Management (a senior-level course with approximately 20
      to 50 students per semester) at the University of Missouri-Columbia are required
      to participate in a simulation exercise that is designed to improve reproductive
      efficiency in a beef herd. During a simulated 5-yr period, students must 1)
      improve reproductive efficiency in a beef cow-herd through implementation of
      reproductive management principles; 2) determine the economic impact of
      reproductive management decisions in a beef herd; and 3) evaluate the constraints
      of different geographical locations on approaches to reproductive management.
      Groups of three to four students are provided with the reproductive and economic
      records of a farm/ranch located in different parts of North America. Students
      create reproductive management plans consisting of 1) detailed discussion of
      farm/ranch environment (climate, terrain, forage and grain availability, and
      stocking rate; season for breeding and calving; and justification for choice of
      breed); 2) assessment of current level of reproductive performance; 3)
      identification and economic justification of specific (measurable) objectives; 4)
      discussion of alternatives for accomplishing specific objectives; 5) prediction
      of reproductive performance (pregnancy rate, quantity of calf weaned per cow
      exposed, and cost per quantity of calf weaned) in response to implementation of
      specific management practices; and 6) an annual and 5-yr reproductive and
      economic summary. Students obtain livestock marketing information for their
      assigned location via the Internet. Spreadsheets were developed to calculate the
      reproductive efficiency of postpartum cows and replacement heifers based on
      management decisions made by the groups and to calculate a yearly economic
      summary for each of the 5 yr. Management decisions are justified in a written
      report, and oral presentations are given to the class when the project is
      completed. Greater than 85% of students indicated that the exercise increased
      their understanding of how management decisions affect reproductive efficiency
      and profitability in a beef operation and also provided added confidence for
      students that applied for beef management positions.

PMID- 15144099
TI  - Disposal of poultry.

PMID- 15144100
TI  - Another ingredient in the recipe for a successful career.

PMID- 15144101
TI  - An ethicist's commentary on placing animals in less-than perfect homes.

PMID- 15144102
TI  - Availability and estimates of veterinary antimicrobial use in British Columbia.
AB  - The amount of antimicrobial use is a significant selection pressure that alters
      the frequency of antimicrobial resistance. This paper summarizes attempts to
      estimate the weight of antimicrobial purchases in British Columbia for use in
      animals. The data reported here do not capture all sources of veterinary
      antimicrobial use in British Columbia. This paper highlights how information
      deficits on veterinary drug use complicate the development of an evidence-based
      policy framework for combating antimicrobial resistance.

PMID- 15144104
TI  - Clinical West Nile virus infection in 2 horses in western Canada.
AB  - Two horses had a history of ataxia and weakness or recumbency. One recovered and
      was diagnosed with West Nile virus (WNV) infection by serologic testing. The
      other was euthanized; it had meningoencephalomyelitis, WNV was detected by
      polymerase chain reaction. West Nile virus infection is an emerging disease. Year
      2002 is the first year in which cases have been seen in Saskatchewan.

PMID- 15144103
TI  - Lack of evidence of Brucella ovis infection in rams in Quebec.
AB  - A study was conducted to estimate the seroprevalence of Brucella ovis infection
      in rams in the Estrie and Bas-Saint-Laurent regions (Quebec). Rams sera (n = 258)
      were serologically evaluated from 224 rams in 30 commercial flocks and from 34
      rams at 2 slaughterhouses by using an enzyme linked immunosorbent assay.
      Epididymides and testes were examined by palpation on farms and microscopically
      for culled rams. No ram was seropositive to Brucella ovis or had lesions
      suggestive of brucellosis from the farm or slaughterhouse surveys.

PMID- 15144106
TI  - Necrotizing hepatitis associated with enteric salmonellosis in an alpaca.
AB  - Salmonella typhimurium was isolated from the feces of an alpaca suffering
      anorexia and weight loss. Multifocal necrotizing and suppurative hepatitis
      consistent with bacterial infection was found in the liver biopsies. Enteric
      salmonellosis may be associated with milder physical and clinicopathological
      changes in camelids than in other large animal species.

PMID- 15144105
TI  - Myxedema coma leading to respiratory depression in a dog.
AB  - A 10-year-old, intact male, cocker spaniel was presented with hypothermia,
      without shivering, and progressive stupor leading to coma. Myxedema coma,
      potentially precipitated by diuretic therapy, was tentatively diagnosed and
      treatment initiated, but progressive respiratory depression led to the decision
      to euthanize. Postmortem findings supported the diagnosis of myxedema coma.

PMID- 15144107
TI  - Obstruction of the small intestine caused by a hairball in 2 young beef calves.
AB  - Two beef calves, with a history of anorexia and absence of feces, were dehydrated
      and bloated on presentation. Intestinal obstruction was suspected based on
      clinical and laboratory findings. Hairballs obstructing the small intestine were
      removed surgically and the calves recovered. Intestinal obstruction due to
      hairballs has not been described before.

PMID- 15144108
TI  - Hepatocellular adenoma in a 12-year-old crossbred German shepherd dog.
AB  - A 12-year-old, neutered male crossbred German shepherd presented with lethargy,
      inappetence, vomiting, and diarrhea. Bile duct carcinoma was diagnosed by
      cytological analysis of samples obtained by ultrasound-guided fine-needle
      aspiration. After surgical excision of the mass, the histologic diagnosis was
      hepatocellular adenoma.

PMID- 15144109
TI  - Inorganic arsenic toxicosis in a beef herd.
AB  - Over a 44-day period, 4 of 5 affected calves in a 170-head herd of beef cattle
      died after exhibiting clinical signs of lethargy, ataxia, anorexia, and diarrhea.
      Histopathological examination of tissues and toxicological analysis of a
      suspicious powder discovered in the pasture confirmed arsenic trioxide toxicosis.

PMID- 15144110
TI  - Animal identification and the veterinary practitioner.

PMID- 15144111
TI  - Adenoma of the nasal turbinate in a sheep.

PMID- 15144112
TI  - The future of veterinary diagnostic laboratories.

PMID- 15144113
TI  - Practical bond considerations: dealing with client emotional or mental limits.

PMID- 15144114
TI  - Sterilizing female dogs.

PMID- 15144115
TI  - CVMA National Benchmarking Program--Part 3.

PMID- 15144116
TI  - Ehlers-Danlos syndrome in a dog.

PMID- 15144117
TI  - Atraumatic proximal femoral physeal fractures in cats.

PMID- 15144118
TI  - Toward an understanding of the long-term outcome of juvenile idiopathic
      arthritis.
AB  - Over the past four decades, a number of studies have evaluated the long-term
      outcome of juvenile idiopathic arthritis (JIA) and some of them have also
      attempted to identify early prognostic factors. This editorial addresses, by
      reviewing the surveys that have analyzed the outcome of JIA in term of clinical
      remission, physical disability, and radiographic damage, the clinical questions
      that are most relevant in this area of study. Altogether, the available data
      indicate that JIA is not a benign disease because a considerable number of
      patients still enter adulthood with persistently active disease and a significant
      proportion of them may develop severe physical disability. Among the different
      onset forms, the long-term outcome is best in persistent oligoarthritis and worst
      in RF-positive polyarthritis; the outcome of systemic arthritis is widely
      variable, perhaps reflecting the heterogeneity of this JIA subtype. The
      comparison of earlier studies with those published in the last decade shows a
      decline in the frequency of patients with severe physical disability over the
      years; however, the proportion of patients who enter adulthood with active
      disease does not seem to be diminished. Although there is considerable data on
      prognostic factors in JIA, prediction of long-term outcome early after disease
      presentation is still difficult because comparisons among studies are hindered
      for a variety of reasons. Thus, while a considerable body of data is
      accumulating, the definition of the long-term outcome of JIA remains imperfect.
      To increase the comparability of future analyses and to obtain generalizable
      information on the prognosis of JIA and its prediction, a great deal of effort
      should be directed toward standardizing the study design and the measurement of
      predictors and outcomes.

PMID- 15144119
TI  - Sequential therapies with intravenous cyclophosphamide and oral mycophenolate
      mofetil or azathioprine are efficacious and safe in proliferative lupus
      nephritis.

PMID- 15144120
TI  - Yersinia enterocolitica leads to transient induction of TNF-alpha and activates
      NF-kappaB in synovial fibroblasts.
AB  - OBJECTIVE: The importance of the presence of bacterial antigen or even living
      bacteria for the pathogenesis of reactive arthritis has been discussed
      increasingly ever since bacterial antigen was found in inflamed joints. Bacteria
      may persist in the body and drive the local immune response, maintaining
      arthritis. Cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) are
      essential for bacterial elimination. In reactive arthritis, the course of the
      disease is influenced by several cytokines, including TNF-alpha. TNF-alpha
      expression can be mediated by transcription factor nuclear factor-kappa B (NF
      kappaB). Moreover, TNF-alpha is also one of the strongest activators of NF
      kappaB. METHODS: In vitro expression of TNF-alpha and activation of NF-kappaB in
      synovial fibroblasts after infection with Yersinia enterocolitica or Salmonella
      enteritidis was analysed by electrophoretic mobility shift assay, Western blot
      assay and real-time PCR. RESULTS: We found that infection of synovial fibroblasts
      with yersinia and salmonellae lead to the transient expression of TNF-alpha mRNA
      and induction of NF-kappaB. CONCLUSION: Induction of TNF-alpha in synovial
      fibroblasts after infection with yersiniae or salmonellae might be insufficient
      to eliminate bacteria, and this could allow the intracellular persistence of
      these bacteria. Our results therefore support the hypothesis that a permissive
      cytokine pattern might contribute to the pathogenesis of reactive arthritis.

PMID- 15144121
TI  - Expression of Ro/SS-A and La/SS-B determined by immunohistochemistry in healthy,
      inflamed and autoimmune diseased human tissues: a generalized phenomenon.
AB  - OBJECTIVE: Autoantibodies to the ribonucleoproteins Ro/SS-A and La/SS-B are found
      in autoimmune diseases such as primary Sjogren's syndrome (pSS), systemic lupus
      erythematousus and rheumatoid arthritis. Increased and aberrant expression of
      Ro/SS-A and La/SS-B in target organs, which have been reported in the recent
      literature, might contribute to their antigenicity. However, data on the
      expression of Ro/SS-A and La/SS-B in other inflammatory conditions are scarce.
      MATERIALS AND METHODS: Using monoclonal antibodies against Ro/SS-A and La/SS-B,
      we studied the expression of these antigens in paraffin-embedded healthy tissue,
      aspecific inflamed tissue, the neonatal and adult cardiac conduction systems and
      labial salivary gland tissues of patients suspected of having pSS. RESULTS: In
      healthy tissues, the nuclei expressed both Ro/SS-A and La/SS-B. This expression
      was stronger in inflamed tissues. Nucleoli were negative and cytoplasmic
      expression was weaker than nuclear expression. No increased or aberrant
      expression of Ro/SS-A or La/SS-B was observed in either neonatal or adult
      atrioventricular nodes and bundle branches. More pSS patients showed high La/SS-B
      immunoreactivity levels in their labial salivary gland ductal cell nuclei than
      non-Sjogren's syndrome sicca patients. CONCLUSIONS: Ro/SS-A and La/SS-B
      expression is a generalized cell biological phenomenon and may be upregulated by
      increased cell activation both in aspecific and autoimmune-mediated inflammation.
      In pSS the high expression of La/SS-B in labial salivary, gland ductal cell
      nuclei might contribute to the local immune response.

PMID- 15144122
TI  - Effects of glucosamine hydrochloride on the production of prostaglandin E2,
      nitric oxide and metalloproteases by chondrocytes and synoviocytes in
      osteoarthritis.
AB  - OBJECTIVES: To determine the response of glucosamine hydrochloride on
      chondrocytes and synoviocytes in terms of prostaglandin E2 (PGE2), nitric oxide
      (NO) and matrix metalloproteases (MMPs). METHODS: Chondrocytes and synoviocytes
      were prepared from joint specimens of patients who underwent total knee
      arthroplasty for osteoarthritis (OA). Chondrocytes from patients with femoral
      neck fracture were served as a normal control. Culture cells were stimulated by 5
      ng/ml of IL-1beta and treated with various concentration of glucosamine
      hydrochloride (from 1 microg/ml to 500 microg/ml). PGE2, NO, MMP-1, MMP-3, and
      MMP-13 levels were evaluated in the culture supernatant. Further, the expression
      of COX-2 mRNA was studied by semiquantitative PCR. RESULTS: With IL-1beta
      stimulation, the levels of these mediators increased dramatically, except for NO
      from synoviocytes. After stimulation, levels of these mediators in OA
      chondrocytes were higher than synoviocytes and normal chondrocytes, and the level
      of MMP-3 was higher than those of MMP-1 and MMP-13. Glucosamine hydrochloride at
      a concentration of 100 microg/ml suppressed PGE2 production, and partly
      suppressed NO production. It also suppressed the production of MMPs from normal
      chondrocytes and synoviocytes but not from OA chondrocytes. CONCLUSION:
      Glucosamine modulates the metabolism of chondrocytes and synoviocytes and its
      mode of action differs between cells and conditions.

PMID- 15144123
TI  - Intra-articular injection of non-animal stabilised hyaluronic acid (NASHA) for
      osteoarthritis of the hip: a pilot study.
AB  - OBJECTIVES: This study was undertaken to assess the safety and potential efficacy
      of intra-articular non-animal stabilised hyaluronic acid (NASHA) in patients with
      hip OA. METHODS: This was a prospective, open-label, 3-month pilot study of a
      single intra-articular injection of NASHA in 31 patients. Safety outcomes were
      measured at 2 weeks and 3 months after treatment, as were efficacy measurements
      including WOMAC pain, stiffness and physical function scores, and the patient
      assessment of global disease status. Patients demonstrating reduced pain at month
      3 participated in an extension phase (assessment at 6-11 months, 18 patients).
      Positive response was defined as a > or = 40% reduction in the WOMAC pain score
      from baseline, together with an absolute decrease of > or = 5 points. RESULTS:
      Intra-articular injection of NASHA into the hip was well tolerated. The only
      treatment-related AE was exacerbation of pain and/or stiffness in the treated hip
      (reported by 9 patients) and there were no serious AEs. The response rate to
      treatment was 50% at 2 weeks and 54% at 3 months. In the extension population,
      response rates of 69% and 44% were observed at month 3 and the extension visit,
      respectively. Global disease status was improved at month 3 compared with
      baseline in 68% of the patients. CONCLUSIONS: Our results show that a single
      intra-articular injection of NASHA is a well tolerated and potentially effective
      therapy in the treatment of hip OA. Further studies of NASHA in this setting are
      warranted.

PMID- 15144124
TI  - The biological action of hyaluronan on human osteoartritic articular
      chondrocytes: the importance of molecular weight.
AB  - OBJECTIVES: The intra-articular injection of hyaluronan (HA) was originally used
      in the treatment of osteoarthritis (OA) to increase the viscosity of synovial
      fluid. However, some findings suggest that the activity of HA cannot be solely
      explained by its biomechanical properties. The aim of this study was to analyze
      the in vitro biological effects of HA on human OA chondrocytes and the impact of
      its molecular weight (MW) on those effects. METHODS: Cells were isolated from
      cartilage obtained during joint replacement surgery in OA patients. The
      chondrocytes were cultured for 24 hours to detect prostaglandin E2 (PGE2) and for
      48 hours to measure nitric oxide (NO), after which they were pre-incubated with
      HA and stimulated with interleukin-1 (IL-1) at 5 ng/ml. Two commercial HA
      preparations with different MWs were used: Hyalgan (500-730 kDa, HA, Bioiberica
      S.A.) and Synvisc (hylan of 6,000 kDa, Biomatrix Inc). NO was detected by the
      Greiss reaction and PGE2 was quantified by a commercial EIA in the supernatant.
      Apoptosis was induced by an NO donor (sodium nitroprusside, SNP) and the effect
      of HA on apoptosis was quantified by flow cytometry. RESULTS: Neither HA
      preparation studied had any effect on the basal production of NO or PGE2.
      However, the 500-730 kDa HA at 200 microg/ml reduced the synthesis of both IL-1
      induced NO and PGE2 by 70% and 45% respectively. Furthermore both HA preparations
      at 200 microg/ml decreased the apoptosis induced by SNP, 500-730 kDa to 40% and
      6,000 kDa to 36%. CONCLUSION: HA may induce biological effects in addition to
      acting as a viscoelastic substance. This study suggests that HA preparations are
      different due to differences in biological activity resulting from MW.

PMID- 15144125
TI  - Clinical determinants of bone mass and bone ultrasonometry in patients with
      systemic sclerosis.
AB  - OBJECTIVE: The aim of this study was to evaluate bone mass and bone
      ultrasonometry in patients affected with systemic sclerosis (SSc). METHODS: Fifty
      five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30
      postmenopausal women) affected with SSc (in a limited, intermediate or diffused
      form) and 60 age-matched healthy controls (30 premenopausal, and 30
      postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan
      beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the
      heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein),
      and autoantibodies (ANA, ENA). Examinations were also carried out in order to
      determine any internal organ involvement. None of the patients had previously
      received steroid treatment. RESULTS: BMD was significantly lower in the SSc group
      than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980
      vs 1.241, p < 0.01; femoral neck: 0.832 vs 0.955, p < 0.05; total body 1.050 vs
      1.168, p < 0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10;
      femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was
      also altered (75.8 vs 96.2, p < 0.01; T = -2.10, Z = -1.12). BMD and SI were
      lower in women with the diffuse form of skin involvement. BMD and SI were lower
      in women in whom one or more internal organs were involved. CONCLUSION: SSc
      patients had reduced BMD and SI that was more marked in the diffuse form and in
      those with internal organ involvement and that became more marked with age and
      estrogen deficiency. This demineralisation was not related to the inflammation
      indices, disease duration, or to the immunological pattern.

PMID- 15144126
TI  - Survey of practices regarding management of early rheumatoid arthritis by
      rheumatologists in France.
AB  - OBJECTIVE: To describe the practices of rheumatologists in France regarding the
      initial management of early rheumatoid arthritis (RA) and to estimate the
      associated costs. METHODS: A questionnaire on the diagnosis and treatment of
      early RA was sent to the 2485 practicing rheumatologists in France. The results
      of the 917 completed questionnaires (37% response rate) were analyzed, and
      initial investigation and treatment costs, including the first month of
      treatment, were calculated from a socio-economic perspective. RESULTS: For the RA
      diagnosis, more than 80% of the respondents recommended the erythrocyte
      sedimentation rate, C-reactive protein, complete blood count, rheumatoid factor,
      antinuclear antibody and wrist radiographs. In 40% and 60% of the cases,
      antikeratin antibody, liver enzymes, serum creatine, serum protein
      electrophoresis and radiographs (chest, foot and knee) were advocated. Initial
      drugs administered were non-steroidal antiinflammatory agents (88%), analgesics
      (76%), disease modifying anti-rheutmatic drugs (74% with methotrexate in 46% of
      cases, followed by hydroxychloroquine [13%], sulfasalazine [8%], leflunomide
      [7%], intramuscular gold therapy [6%]), and glucocorticoids (21%). Rehabilitation
      was recommended by 51% of the respondents. The median cost for this initial
      management was 273 euros (mean 301 euros, range 49-1,336 euros). CONCLUSION:
      Marked variations occur among French rheumatologists in the initial management of
      early RA. These data may be helpful in identifying obstacles to physician
      compliance with recommendations regarding everyday clinical practice and to set
      up more a specific evaluative study.

PMID- 15144127
TI  - Safety of leflunomide plus infliximab combination therapy in rheumatoid
      arthritis.
AB  - OBJECTIVE: To analyse the safety of leflunomide plus infliximab combination
      therapy, in adult rheumatoid arthritis (RA) patients. PATIENTS: A retrospective
      study of 17 adult patients with active RA (DAS 28 = 5.94 +/- 0.88 at baseline)
      who were treated with a combination of leflunomide plus infliximab after failure
      of treatment with other DMARDs. 13 patients were treated for a minimum of 3
      months with leflunomide without toxicity before beginning infliximab. Treatment
      was begun simultaneously with both drugs in 4 patients. Side effects (clinical
      and biological) and efficacy (DAS 28) were evaluated at each infliximab infusion
      (3 mg/kg at week 0, 2, 6 and then every 8 weeks). RESULTS: Thirteen patients
      experienced 20 types of side effects and 8 of them stopped the combination
      therapy. The causes of discontinuation were congestive heart failure (1 case),
      hypertension with thoracic pain (2 cases), eczematous skin patches (2 cases) and
      neutropenia (3 cases). No death was registered. Nine RA patients continuted the
      therapy with a median follow-up of 22 weeks. Only 4 of them experienced no side
      effects. Eight patients were positive for antinuclear antibodies (ANA) and 1 for
      double-stranded DNA (dsDNA) antibodies at study entry. After treatment, 13 and 5
      patients tested positive respectively for ANAs and dsDNA antibodies. There was no
      relationship between discontinuation and ANA/dsDNA positivity. CONCLUSION: In
      this cohort, adverse events were not very different from those seen in patients
      on either treatment alone and the combination of leflunomide plus infliximab did
      not appear to be as badly tolerated as described in a previous study.

PMID- 15144128
TI  - CD69 expression on neutrophils from patients with rheumatoid arthritis.
AB  - OBJECTIVE: Since the early activation antigen CD69 has been implicated in the
      pathogenesis of some inflammatory diseases, we evaluated the expression of the
      molecule on peripheral blood (PB) and synovial fluid (SF) neutrophils obtained
      from RA patients and its possible correlation with PB and SF cytokine
      concentration. METHODS: CD69 membrane expression (and CD11b as control marker)
      was assessed by indirect immunofluorescence and flow cytometry analysis on
      purified PB and SF neutrophils. Cytokine levels (GM-CSF, IFN-gamma, TNF-alpha) in
      plasma and SF supernatants were measured by ELISA. RESULTS: CD69 was absent on
      control neutrophils, while it was expressed on PB neutrophils from RA patients
      although no detectable GM-CSF, IFN-gamma or TNF-alpha was observed in their
      plasma. CD69 expression was still more evident on SF neutrophils from RA
      patients; 59% had detectable levels of INF-gamma in their SF while GM-CSF and TNF
      alpha were detectable in SF from 95% and 33% of RA patients, respectively.
      However, no correlation was observed between cytokine concentrations and CD69
      expression on SF neutrophils. SF but not PB neutrophils from RA patients
      expressed increased amounts of CD11b when compared to control PB neutrophils
      without any correlation with CD69 membrane expression. CONCLUSION: The activation
      antigen CD69 is significantly expressed on PB and SF neutrophils from RA
      patients. However, the mechanism(s) of induction and its possible role in the
      pathogenesis of RA remain to be defined.

PMID- 15144129
TI  - MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and
      psoriatic arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) are both
      chronic rheumatic inflammatory diseases characterized by disruption of the extra
      cellular matrix (ECM) protein of the cartilage, likely induced by proteolytic
      enzymes such as matrix metalloproteases (MMPs). The goal of this study was to
      quantify the expression of MMPs such as MMP-2 and MMP-9, and their physiological
      tissue inhibitors TIMP-2 and TIMP-1, respectively, in serum and synovial fluid.
      METHODS: Serum and synovial fluid from 24 RA patients and 17 PA patients were
      studied to determine the levels of MMP-2 and MMP-9 proteolytic activity using a
      modified gelatin zymography procedure. TIMP-1 and TIMP-2 were measured by a
      commercially available ELISA kit. RESULTS: Our results show that MMP-2 was
      detected in the latent form only, while MMP-9 was present in latent and active
      form. Both gelatinases were more concentrated in synovial fluid than in serum,
      and TIMP-1 and TIMP-2 concentrations were also more elevated in synovial fluid
      than in serum. CONCLUSIONS: To investigate the remodelling of cartilage ECM
      proteins, the evaluation of synovial fluid concentrations of MMP-2, MMP-9, TIMP-1
      and TIMP-2 is more reliable than that determined in serum. In view of these data,
      MMPs inhibitors might represent a possible target for new therapies delivered
      directly in the joint space.

PMID- 15144130
TI  - Is there a role for Chlamydia pneumoniae infection in systemic lupus
      erythematosus and in the associated atherosclerotic cardiovascular disease?
AB  - OBJECTIVE: To search for molecular evidence of Chlamydial infection in systemic
      lupus erythematosus (SLE) subjects and to assess if there is an association of
      this infectious agent with coronary artery calcification (CAC), a marker of total
      atherosclerotic burden. METHODS: 28 SLE subjects had blood samples drawn and DNA
      extracted from peripheral blood mononuclear cells (PBMC) and an electron beam
      computed tomography (EBCT) scan. Polymerase chain reaction (PCR) analysis was
      performed for Chlamydia trachomatis 16srRNA and major outer membrane protein
      (MOMP) and for C. pneumoniae 16srRNA, MOMP, as well as nested PCR for MOMP.
      RESULTS: Four of 28 subjects (14.2%) had evidence of C. pneumoniae nucleic acid
      in PBMC. The 16srRNA primers detected C. pneumoniae in one patient (3.57%) and
      the nested PCR MOMP primers in 3 subjects (10.71%). None were positive for
      Chlamydia trachomatis. Two of the 4 subjects with C. pneumoniae DNA had abnormal
      EBCT scans and 2/11 (18.3%) subjects with abnormal EBCT were positive for C.
      pneumoniae. There were significant associations of C. pneumoniae DNA with smoking
      (OR = 3) and corticosteroid use. The odds ratio for subjects with abnormal CAC
      and detectable C. pneumoniae was 1.67. CONCLUSION: This pilot study demonstrates
      for the first time that C. pneumoniae DNA can be identified in the PBMC of some
      SLE subjects and there may be an association with CAC. Smoking may be an
      additional risk factor for infection in this population. Determination of
      pathogenicity of this organism in atherosclerotic coronary vascular disease in
      SLE will require further study.

PMID- 15144131
TI  - Osteoarticular mycobacterial infections in patients with the human
      immunodeficiency virus.
AB  - OBJECTIVE: Data about the characteristics of patients with the human
      immunodeficiency virus (HIV) and concomitant mycobacterial skeletal infection are
      scarce. Thus, our aim was to describe this condition in a cohort of 11 patients.
      METHODS: A review of the records of 11 HIV-positive individuals with
      microbiological confirmation of mycobacterial osteoarticular infection was
      conducted. The studied data included: age, sex, risk factor for the HIV days
      between the onset of symptoms and diagnosis, evidence of previous tuberculosis,
      location of the infection, isolated organism, diagnostic method, laboratory data
      (erythrocyte sedimentation rate, haemoglobin, leukocyte count), number of CD4+
      lymphocytes, anti-retroviral therapy, treatment and outcome. RESULTS: Eight
      patients were men and 3 were women. The median age was 34.2 years (range 20-46
      years). Previous tuberculosis was present in 5 cases. Mean days between the onset
      of symptoms and diagnosis was 124 (range 20-365 days). Infections involved the
      knee (4 cases), spine (3 cases), hip (2 cases), elbow (1 case) and tibia (1
      case). ESR was frequently elevated. The CD4 count ranged from 0.03 to 0.779 x
      10(9)/l (mean 0.245 x 10(9)/l). M. tuberculosis was the responsible organism in 9
      cases, Mycobacerium tuberculosis plus Staphylococcus aureus in one case and M.
      Kansasii in one case. Patients received specific treatments with good results.
      Surgery was necessary in 4 cases. No deaths occurred. Four patients were anti
      retroviral naive at the moment the diagnosis was made. The remainder 8 were on
      zidovudine therapy. CONCLUSION: The immunologic status of patients with HIV and
      concomitant mycobacterial skeletal infections is quite variable. The outcome of
      this condition seems to be good.

PMID- 15144132
TI  - Takayasu's arteritis secondary to myelodysplasia as a predictor of poor outcome:
      two case reports.
AB  - We present two patients with myelodysplasia in association with Takayasu's
      arteritis (TA). In both patients intensive immunosuppressive treatment could not
      control the vascular inflammation. Subsequently both patients developed
      myelodysplasia, rapidly progressing to secondary acute myelogenous leukaemia. One
      patient had a peripheral blood stem cell transplant from a compatible sibling
      donor, but died of refractory leukaemia 5 months later. The other patient died of
      fungal sepsis. These are the first two patients reported to have TA associated
      with myelodysplasia/secondary leukaemia.

PMID- 15144133
TI  - Appropriateness in anti-nuclear antibody testing: from clinical request to
      strategic laboratory practice.
AB  - As a result of rapid changes in laboratory technology, clinical behaviour and
      patients' expectations, along with limited economic resources, there is a greater
      requirement for an appropriate use of autoantibody testing. We examine the
      various aspects and the most controversial points of the diagnostic procedure in
      systemic autoimmune rheumatic diseases, and make recommendations for the most
      efficient approach to autoantibody testing, based on selected publications and
      the relevant literature. Appropriateness is a complex task that can be achieved
      only by combining the efforts from the laboratory and the clinic, thereby using
      scientific knowledge, inter-disciplinary consultation and expert clinical
      investigation.

PMID- 15144134
TI  - Serological assessment of type I collagen burden in scleroderma spectrum
      disorders: a systematic review.
AB  - RATIONALE: The aim of the study was to evaluate the validity of collagen type I
      metabolites as markers of disease activity in scleroderma (SSc), through a
      systematic review of the literature and by validating the results by measuring
      collagen type I metabolites in well characterized patients with scleroderma
      spectrum disorders and in Raynaud's phenomenon. METHODS: A systematic review was
      performed of studies of collagen type I metabolites in scleroderma spectrum
      disorders published from 1980 to 2003. The collected results from the literature
      were compared with our own measurements of collagen type I metabolites (PINP and
      ICTP) in a small number of well characterized patients within the scleroderma
      spectrum and in patients with primary and "autoimmune" Raynaud's phenomenon.
      Peptide concentrations from all sources, including the present study, were
      compared. Reported correlations between peptide concentrations and clinical
      variables were also analysed. RESULTS: Of 19 papers identified by an extensive
      Medline search, 12 were eligible for systematic analysis. There was a
      considerable heterogeneity in the results with a wide range of metabolite
      concentrations. Values from disease groups and healthy controls overlapped. These
      findings were confirmed by our study where, similarly, there was a large range of
      values in all groups, but particularly in the diffuse SSc subset. When the
      correlation between peptide levels and clinical variables was assessed, large
      discordance between the studies was observed. CONCLUSIONS: We have not found
      sufficient evidence to support the use of serum markers of collagen turnover in
      the assessment of scleroderma activity and severity, in view of their low
      specificity and the heterogeneity of the results of various studies. Lack of
      standardized routine evaluation of SSc patients in clinical studies might have
      accounted for the variability of the findings. However, due to the small sizes of
      most published studies, demonstration of no effect should come from large-scale
      randomised trials. Longitudinal serial analysis of these molecules in individual
      patients may play a future role in the evaluation of the response to fibroblast
      targeting therapeutic strategies in scleroderma patients.

PMID- 15144135
TI  - Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: An unsolved problem in juvenile idiopathic arthritis (JIA) is to
      identify patients at special risk for relapse. It is important to adjust anti
      inflammatory and immunosuppressive therapy to the children's actual disease
      activity especially in times of remission. Our aim was to analyze if the serum
      levels of MRP8/MRP14 are reliable predictive markers for the risk of relapse in
      clinically inactive juvenile idiopathic arthritis. METHODS: Serum concentrations
      of MRP8/MRP14 were determined by ELISA and correlated with laboratory and
      clinical parameters for disease activity in patients with JIA. 29 patients with
      changing disease activity were followed up for a mean time of 2.9 years. Two
      groups of patients--one before relapse (mean 3.7 months) but without clinical
      signs of disease reactivation, and one in remission for 12 further months--were
      compared. RESULTS: MRP8/MRP14 serum levels in patients before relapses were
      significantly higher than the levels in patients in stable remission for one year
      (662 ng/ml versus 395 ng/ml; p < 0.05). Using a cut-off for MRP8/MRP14 of 450
      ng/ml the likelihood ratio for relapse was 3.7 (positive predictive value 80%),
      while no differences were found for C-reactive protein and erythrocyte
      sedimentation rate between the two groups. CONCLUSION: MRP8/MRP14 correlate with
      individual disease activity in patients with JIA. Our data suggest that local
      disease activity may be present even months before flares become clinically
      apparent. Serum levels of MRP8/MRP14 can give a hint as to clinically occult
      disease activity, in this way helping to adjust therapy in times of low disease
      activity.

PMID- 15144136
TI  - Interleukin-4 receptor alpha polymorphisms in primary Sjogren's syndrome.

PMID- 15144137
TI  - Fulminant hepatitis in an asymptomatic chronic carrier of hepatitis B virus
      mutant after withdrawal of low-dose methotrexate therapy for rheumatoid
      arthritis.

PMID- 15144138
TI  - Silicone gel filled breast implants and dermatomyositis.

PMID- 15144139
TI  - Lupus-like onset of recurrent Kawasaki disease in an adolescent boy.

PMID- 15144140
TI  - A case of Kawasaki disease accompanied by Henoch-Schonlein purpura.

PMID- 15144141
TI  - Clarithromycin in adult-onset Still's disease. Case report with a 1-year follow
      up.

PMID- 15144142
TI  - Juvenile temporal arteritis: a case report and review of the literature.

PMID- 15144143
TI  - Could placental abruption be an antiphospholipid antibody related disorder?

PMID- 15144144
TI  - Pulse steroid treatment of polymyalgia rheumatica.

PMID- 15144145
TI  - Beta-thalassaemic trait and systemic lupus erythematosus.

PMID- 15144146
TI  - Monolateral coxitis as a unique osteoarticular manifestation of Parvovirus B19
      infection.

PMID- 15144147
TI  - Comparison of serum IgE levels between female and male SLE patients, with
      reference to gender differences in the incidence of SLE.

PMID- 15144148
TI  - A matter of attitude.

PMID- 15144149
TI  - Best use for PAs and NPs.

PMID- 15144150
TI  - The perils of single-payer health care.

PMID- 15144152
TI  - Nurses study hospital noise.

PMID- 15144151
TI  - Medical schools teach safety.

PMID- 15144153
TI  - ICSI action group tackles safety.

PMID- 15144154
TI  - Malpractice crisis impedes safety.

PMID- 15144155
TI  - Safety and quality: our common goals.

PMID- 15144156
TI  - Embrace EMRs.

PMID- 15144157
TI  - Imperfect tools.

PMID- 15144158
TI  - Putting patient safety in place.

PMID- 15144159
TI  - Lifelike learning.

PMID- 15144160
TI  - Health literacy and patient safety.

PMID- 15144161
TI  - A call for improving quality in care transitions.

PMID- 15144162
TI  - A better system for monitoring and preventing medical errors.

PMID- 15144163
TI  - Reducing medication errors: safest in America targets error-prone prescribing
      practices.

PMID- 15144164
TI  - Balanced scorecards for specialists: a tool for quality improvement.
AB  - This article describes a program that HealthPartners uses to assess and compare
      the performance of specialists that serve its members. HealthPartners' Balanced
      Scorecards program focuses on cardiologist and orthopedist practices in the
      Minneapolis/St. Paul metro area and St. Cloud, Minnesota. The scorecards assess
      the clinical and business processes of specialist practices, their use of
      resources, the degree to which patients and referring physicians are satisfied
      with their performance, and their patient outcomes. Unblinded comparative data is
      made available to referring physicians, employers, and consumers only after each
      individual specialist group has had the opportunity to review its own data
      against blinded results, discuss the methodology, and comment on the results.

PMID- 15144166
TI  - Another sore throat.

PMID- 15144165
TI  - From eminence-based practice to evidence-based practice: a paradigm shift.
AB  - Evidence-based medicine differs from the traditional approach to health care in
      that in addition to relying on clinical experience, expert opinion, and knowledge
      of pathophysiology for clinical decision-making, clinicians identify important
      knowledge gaps and information needs, formulate answerable questions, identify
      potentially relevant research, assess the validity of evidence and results, and
      apply research evidence to individual patients in a way that takes into account
      the patients' particular experiences, expectations, and values. It is becoming
      increasingly important that physicians learn the concepts of EBM because many EBM
      related concepts have become a part of daily clinical practice. This article uses
      examples from orthopedics to outline EBM principles and methods and the
      advantages of EBM over traditional approaches. It also discusses challenges in
      implementing EBM and suggests EBM-related resources for physicians.

PMID- 15144167
TI  - Insurance coverage and the states.

PMID- 15144168
TI  - Ethnic politics, policy fragmentation, and dependent health care access in
      California.
AB  - One out of every six nonelderly Americans without health insurance lives in
      California. The problem of access to competent and dependable health care is
      especially problematic among the state's minority, and especially Hispanic,
      population. Because one-third of the country's Hispanics live in California, how
      this state deals with health access issues will affect the practice and progress
      toward universal care in the nation as a whole. Expanding health care access to
      California's dependent population will involve overcoming a number of well-known
      administrative and fiscal obstacles, including an underfunded, highly fragmented
      public health care system that has developed incrementally and incoherently over
      decades. However, a key to understanding the problem of access to health care in
      California involves a story of how ethnic conflict and partisan politics often
      conspire to deny or discourage access for eligible women and children.

PMID- 15144169
TI  - Holding back the tide: policies to preserve and reconstruct health insurance
      coverage in Maryland.
AB  - Over the past decade, state officials have pursued a variety of strategies to
      protect and expand health insurance coverage for their residents. This article
      examines the course of action in Maryland, where new initiatives were shaped
      around the state's unique hospital payment system and its reimbursement of
      uncompensated care, an evolving Medicaid and children's health program, and
      regulation of the small group health insurance market. Several important patterns
      emerge from the Maryland experience. First, even the most incremental initiatives
      -programs intended to aid a few thousand beneficiaries--bring into play the very
      issues that hamper comprehensive reforms: who is deserving of mutual aid and what
      is the proper role of government versus private entities in administering that
      aid. In Maryland, these issues generate conflict not only between Democrats and
      Republicans but also urban and rural interests. Second, all of the important
      reforms of the past decade were undertaken primarily in reaction to federal
      policy initiatives. Contrary to rhetoric lauding states as the "laboratories of
      democracy," the political impetus for reform and basic policy options emerge from
      interaction between federal and state debates. Third, even with budget surpluses
      and Democrats in control of the governorship and legislature, Maryland did not
      move aggressively toward universal health insurance. Now, with a much weaker
      economy and a new, Republican governor, the primary challenge will be to prevent
      further erosion of insurance coverage. The Maryland experience reiterates that
      each step toward greater health security, no matter how small, is a major
      technical and political challenge and that it will be difficult if not impossible
      to rely on states to secure coverage for all Americans in the foreseeable future.

PMID- 15144170
TI  - Obstacles to dependent health care access in Oregon: health insurance or health
      care?
AB  - In the 1980s, Oregon was one of a handful of "states that could not wait" for
      national health care reform. Oregon's chosen approach to reform was predicated on
      two widely accepted assumptions. First, universal access to health care is best
      achieved by universal access to health insurance. Second, universal access to
      health care could best be achieved, at least politically, by incrementally
      building upon the existing health care delivery and insurance system. This
      article questions both of these assumptions in light of Oregon's decade-long
      experience in trying to expand access to health care among its dependent
      population.

PMID- 15144171
TI  - States and the politics of incrementalism: health policy in Wisconsin during the
      1990s.
AB  - Wisconsin officials during the 1990s seemed poised to enact innovative and
      comprehensive health care reform. During that era, an ambitious, popular, and
      reform-minded governor led the state. The state had an unusually professional
      legislature. The state's economy was strong. Even with these advantages, however,
      the report card on the state's efforts is mixed. The state enacted a fairly
      modest set of reforms that were financed largely by the federal government and
      subject to extensive federal oversight. The Wisconsin story thus seems to be
      about the politics of incrementalism. But while critics of incrementalist
      politics point out that the number of uninsured continues to grow, the catalytic
      federalism witnessed in Wisconsin in the 1990s may well be the best model for
      implementing health care reform.

PMID- 15144172
TI  - State health care reform politics and the unfortunate end of the 1990s.

PMID- 15144173
TI  - State efforts to expand health coverage: one bite at a time.

PMID- 15144174
TI  - Basal plane pyrolytic graphite modified electrodes: comparison of carbon
      nanotubes and graphite powder as electrocatalysts.
AB  - The oxidations of NADH, epinephrine, and norepinephrine are studied using carbon
      nanotube and graphite powder-modified basal plane pyrolytic graphite electrodes.
      Immobilization is achieved in two ways: first, via abrasive attachment of
      multiwall carbon nanotubes or graphite powder by gently rubbing the electrode
      surface on a fine quality paper supporting the desired material; second, via
      "film" modification from dispersing either graphite powder or nanotubes in
      acetonitrile and pipeting a small volume onto the electrode surface and allowing
      the solvent to volatilize. While electrocatalytic behavior of both types of
      nanotube-modified electrodes is shown, with enhanced currents and reduced peak-to
      peak separations in the voltammetry in comparison with naked basal plane
      pyrolytic graphite, similar catalytic behavior is also seen at the graphite
      powder-modified electrodes. Caution is, therefore, suggested in assigning unique
      catalytic properties to carbon nanotubes.

PMID- 15144175
TI  - Electrogenerated chemiluminescence from R(bpy)3(2+) ion-exchanged in carbon
      nanotube/perfluorosulfonated ionomer composite films.
AB  - The electrochemistry and electrogenerated chemiluminescence (ECL) of
      ruthenium(II) tris(bipyridine) (Ru(bpy)(3)(2+)) ion-exchanged in carbon nanotube
      (CNT)/Nafion composite films were investigated with tripropylamine (TPA) as a
      coreactant at a glassy carbon (GC) electrode. The major goal of this work was to
      investigate and develop new materials and immobilization approaches for the
      fabrication of ECL-based sensors with improved sensitivity, reactivity, and long
      term stability. Ru(bpy)(3)(2+) could be strongly incorporated into Nafion film,
      but the rate of charge transfer was relative slow and its stability was also
      problematic. The interfusion of CNT in Nafion resulted in a high peak current of
      Ru(bpy)(3)(2+) and high ECL intensity. The results indicated that the composite
      film had more open structures and a larger surface area allowing faster diffusion
      of Ru(bpy)(3)(2+) and that the CNT could adsorb Ru(bpy)(3)(2+) and also acted as
      conducting pathways to connect Ru(bpy)(3)(2+) sites to the electrode. In the
      present work, the sensitivity of the ECL system at the CNT/Nafion film-modified
      electrodes was more than 2 orders of magnitude higher than that observed at a
      silica/Nafion composite film-modified electrode and 3 orders of magnitude higher
      than that at pure Nafion films. The CNT/Nafion composite film-modified GC
      electrodes also exhibited long-term stability.

PMID- 15144176
TI  - Potentiometric sensing of chemical warfare agents: surface imprinted polymer
      integrated with an indium tin oxide electrode.
AB  - Rapid and specific recognition of methylphosphonic acid (MPA), the degradation
      product of nerve agents sarin, soman, VX, etc., was achieved with potentiometric
      measurements using a chemical sensor fabricated by a surface imprinting technique
      coupled with a nanoscale transducer, indium tin oxide (ITO). An octadecylsiloxane
      thin layer was covalently bound to the ITO-coated glass surface in the presence
      of MPA. After extraction of MPA, potentiometric measurements showed selective
      detection of MPA. The selectivity of the sensor has been tested on other
      alkylphosphonic acids, such as ethylphosphonic acid and propylphosphonic acid, as
      well as tert-butylphosphonic acid. The viability of the sensor in the presence of
      other chemical analogues, such as organophosphorus pesticides and herbicides, was
      investigated.

PMID- 15144177
TI  - Iterative absolute electroanalytical approach to characterization of bulk redox
      conducting systems.
AB  - A novel electroanalytical approach is proposed here, and it is demonstrated with
      the direct and simultaneous determination of two unknowns: the concentration of
      redox sites and the apparent diffusion coefficient for charge propagation in a
      single crystal of dodecatungstophosphoric acid. This Keggin-type polyoxometalate
      serves as a model bulk redox conducting inorganic material for solid-state
      voltammetry. The system has been investigated using an ultramicrodisk working
      electrode in the absence of external liquid supporting electrolyte. The
      analytical method requires numerical solution of the combination of two equations
      in which the first one describes current (or charge) in a well-defined (either
      spherical or linear) diffusional regime and the second general equation describes
      chronoamperometric (or normal pulse voltammetric current) under mixed (linear
      spherical) conditions. The iterative approach is based on successive
      approximations through calculation and minimizing the least-squares error
      function. The method is fairly universal, and in principle, it can be extended to
      the investigation of other bulk systems including sol-gel processed materials,
      redox melts, and solutions on condition that they are electroactive and well
      behaved, they contain redox centers at sufficiently high level, and a number of
      electrons for the redox reaction considered is known.

PMID- 15144179
TI  - Hydrodynamic dispersion due to combined pressure-driven and electroosmotic flow
      through microchannels with a thin double layer.
AB  - The hydrodynamic dispersion of a nonadsorbed and nonelectrolyte solute is
      considered for the case of a flow driven through a straight microchannel by
      pressure and electric potential differences. The analysis is conducted using a
      thin double layer approximation developed in the previous paper (Zholkovskij, E.
      K.; Masliyah, J. H.; Czarnecki, J. Anal. Chem. 2003, 75, 901-909). On the basis
      of this approach, an expression is derived to address the dispersion coefficient
      for arbitrary electrokinetic potential, electrolyte type, and cross-section
      geometry. In the derived expression, the influence of cross-section geometry
      manifests itself through the channel hydrodynamic radius and through three
      dimensionless geometrical factors. The procedure for obtaining the geometrical
      factors is presented for an arbitrary cross-section geometry. The geometrical
      factors are evaluated for several examples of cross section: (i) unbounded
      parallel planes; (ii) circle; (iii) annulus; (iv) ellipse; (v) rectangle. The
      dependency of the dispersion coefficient on different parameters is discussed. It
      is shown that the dependencies are substantially affected by the cross-section
      geometry, electrolyte type, and electrokinetic potential.

PMID- 15144178
TI  - Bead-based electrochemical immunoassay for bacteriophage MS2.
AB  - Viruses are one of four classes of biothreat agents, and bacteriophage MS2 has
      been used as a simulant for biothreat viruses, such as smallpox. A paramagnetic
      bead-based electrochemical immunoassay has been developed for detecting
      bacteriophage MS2. The immunoassay sandwich was made by attaching a biotinylated
      rabbit anti-MS2 IgG to a streptavidin-coated bead, capturing the virus, and then
      attaching a rabbit anti-MS2 IgG-beta-galactosidase conjugate to another site on
      the virus. beta-Galactosidase converts p-aminophenyl galactopyranoside (PAPG) to
      p-aminophenol (PAP). PAPG is electroinactive at the potential at which PAP is
      oxidized to p-quinone imine (PQI), so the current resulting from the oxidation of
      PAP to PQI is directly proportional to the concentration of antigen in the
      sample. The immunoassay was detected with rotating disk electrode (RDE)
      amperometry and an interdigitated array (IDA) electrode. With an applied
      potential of +290 mV vs Ag/AgCl and a rotation rate of 3000 rpm, the detection
      limit was 200 ng/mL MS2 or 3.2 x 10(10) viral particles/mL with RDE amperometry.
      A trench IDA electrode was incorporated into a poly(dimethyl siloxane) channel,
      within which beads were collected, incubated with PAPG, and PAP generation was
      detected. The two working electrodes were held at +290 and -300 mV vs Ag/AgCl,
      and electrochemical recycling of the PAP/PQI couple by the IDA electrode lowered
      the limit of detection to 90 ng/mL MS2, or 1.5 x 10(10) MS2 particles/mL.

PMID- 15144180
TI  - Mechanistic investigation of nanoparticle motion in pulsed voltage miniaturized
      electrical field flow fractionation device by in situ fluorescence imaging.
AB  - In our previous study, we reported a miniaturized electrical field flow
      fractionation device (micro-EFFF) that used a pulsed voltage (PV) to increase the
      effective electric field and, hence, improved the separation performance. In this
      work, we developed two micro-EFFFs with planar or segmented electrode design and
      investigated the particle movement in the flow channels under a PV. Numerical
      simulation was used to understand the electric field distribution in the micro
      EFFFs. When the calculations for the micro-EFFF with a segmented electrode
      (segmented micro-EFFF) and the micro-EFFF with planar electrodes (planar micro
      EFFF) are compared, a stronger electric field at the top electrode segments is
      found in the segmented micro-EFFF, with the strongest field at the edges of the
      electrode segments. Nanoparticle motion in both devices was in situ visualized by
      using a fluorescence microscope equipped with a CCD-camera. Results reveal that
      electrophoresis governs the nanoparticle movement in the planar micro-EFFF and
      dielectrophoresis dominates the movement in the segmented micro-EFFF. Two models
      are postulated to explain the experimental observations of the nanoparticle
      movement. The mechanistic understanding of controlling nanoparticle motion in a
      miniaturized environment will help the design and application of micro-EFFF for
      the separation of charged biomolecules (proteins and DNAs).

PMID- 15144181
TI  - Theoretical modeling and experimental evaluation of a microscale molecular mass
      sensor.
AB  - A theoretical model for a recently developed microscale molecular mass sensor
      (micro-MMS) is presented. The micro-MMS employs a widely applicable technique of
      measuring the refractive index gradient (RIG) in a microchannel created after two
      adjacent streams merge: a "sample stream" containing analyte(s) of interest in a
      host solvent and a "mobile-phase" stream containing only the host solvent.
      Because the flow in the microchannel is laminar, the analytes in the sample
      stream mix with the mobile-phase stream primarily by diffusion. The diffusion
      induced RIG in the microchannel is measured by monitoring the deflection angle of
      a diode laser probe beam, which is orthogonal to both the direction of flow and
      the direction of analyte diffusion. The micro-MMS samples the RIG with probe
      beams at two positions along the direction of flow, and the ratio of the
      downstream to the upstream signal monitors the diffusion coefficient. Following
      calibration for a given class of compounds, the molecular mass of an analyte of
      interest can be determined. Along with the analyte diffusion coefficient, the
      theoretical model indicated three other specific parameters are important to
      interpret the micro-MMS output: the radius of the interrogating light probe
      beams, the time intervals between each of the detection positions, and the merge
      point relative to the detection positions. A series of experiments were conducted
      at different beam radii and flow rates to investigate these parameters, and the
      results are consistent with the model. The model shows that by using smaller beam
      radii and altering flow rates the molecular mass range of the micro-MMS can be,
      in principle, tuned from less than 10(2) g/mol to greater than 10(8) g/mol. The
      ratio data from the micro-MMS is also demonstrated to readily provide a
      "universal calibration", from which the determination of unknown diffusion
      coefficients can be readily obtained.

PMID- 15144182
TI  - Protein characterization by on-line capillary isoelectric focusing, reversed
      phase liquid chromatography, and mass spectrometry.
AB  - Two-dimensional polyacrylmide gel electrophoresis (2D-PAGE), perhaps the most
      widely used method in proteomics research, is often limited by sensitivity and
      throughput. Capillary isoelectric focusing (CIEF) coupled with electrospray
      ionization (ESI) mass spectrometry (MS) provides a liquid-based alternative to 2D
      PAGE that can overcome these problems but is limited by ampholyte interference
      and signal quenching in ESI-MS. Inserting a reversed-phase liquid chromatography
      (RPLC) step between CIEF and MS can remove this interference. In this work, a
      CIEF-RPLC-MS system is described for separation and characterization of proteins
      in complex mixtures. CIEF is performed with a microdialysis membrane-based
      cathodic cell that also permits protein fractions to be collected, washed to
      remove ampholyte, and analyzed by RPLC-MS. CIEF performance with this cell is
      equivalent to that achieved with a conventional cathodic cell, and no loss of
      protein is observed during faction collection. The cell can be easily and safely
      retrofitted into commercial instrumentation and is applicable for peptide
      analysis as well. Protein detection at the low-femtomole level is demonstrated
      with little or no interference from ampholyte, and CIEF-RPLC-MS data are used to
      construct a plot of pI vs MW for a protein mixture. The current instrumental
      configuration allows seven fractions in the pI range 3-10 to be analyzed by RPLC
      MS in 2 h.

PMID- 15144183
TI  - Secondary electrospray ionization-ion mobility spectrometry for explosive vapor
      detection.
AB  - The unique capability of secondary electrospray ionization (SESI) as a
      nonradioactive ionization source to detect analytes in both liquid and gaseous
      samples was evaluated using aqueous solutions of three common military
      explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG)
      and pentaerythritol tetranitrate (PETN). The adducts formed between the compounds
      and their respective dissociation product, RDX.NO(2)(-), NG.NO(3)(-), and
      PETN.NO(3)(-), gave the most intense signal for the individual compound but were
      more sensitive to temperature than other species. These autoadducts were
      identified as RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-) and had maximum signal
      intensity at 137, 100, and 125 degrees C, respectively. The reduced mobility
      values of the three compounds were constant over the temperature range from 75 to
      225 degrees C. The signal-to-noise ratios for RDX, NG, and PETN at 50 mg L(-1) in
      methanol-water were 340, 270, and 170, respectively, with a nominal noise of 8 +/
      2 pA. In addition to the investigation of autoadduct formation, the concept of
      doping the ionization source with nonvolatile adduct-forming agents was
      investigated and described for the first time. The SESI-IMS detection limit for
      RDX was 116 microg L(-1) in the presence of a traditional volatile chloride
      dopant and 5.30 microg L(-1) in the presence of a nonvolatile nitrate dopant. In
      addition to a lower detection limit, the nitrate dopant also produced a greater
      response sensitivity and a higher limit of linearity than did the traditional
      volatile chloride dopant.

PMID- 15144184
TI  - Guanidino labeling derivatization strategy for global characterization of peptide
      mixtures by liquid chromatography matrix-assisted laser desorption/ionization
      mass spectrometry.
AB  - Guanidination performed with isotopic isoforms of O-methylisourea was used in
      combination with reversed-phase liquid chromatography (LC) matrix-assisted laser
      desorption/ionization to characterize, both qualitatively and quantitatively,
      protein mixtures. Synthesis of (13)C- and (15)N(2)-labeled O-methylisourea
      sulfate produces a molecule that is 3 Da heavier than the light isotopic variant.
      Protein mixtures containing identical components in different concentration are
      pooled together following parallel derivatization. Relative quantification of
      protein mixtures is achieved by mass spectrometry. A difference of 3 Da allows
      negligible interference between the two isotopic clusters for quantification of
      peptides up to 1400 Da. Under these conditions, the chromatographic resolution
      achieved allows separation of different pairs of derivatized peptides without
      altering the retention time of structurally identical isotopic isoforms.
      Concomitant isolation of both chemically modified precursors is followed by
      tandem mass analysis. Activation of the ions via collisions with an inert gas
      produces isotopically derivatized fragment ions, which appear as doublets in the
      product ion spectrum. Since the modification occurs on the C-terminal lysine,
      ions incorporating the guanidino moiety on the C-terminus can be distinguished
      from those containing the original unmodified peptide N-terminus. Knowledge of
      the location of the proton can be beneficial to data interpretation and peptide
      sequencing.

PMID- 15144185
TI  - Use of statistical methods for estimation of total number of charges in a mass
      spectrometry experiment.
AB  - Estimation of the number of ions in a mass spectrometry experiment is needed to
      determine instrumentation parameters such as ionization efficiency, collision
      induced dissociation efficiency, ion-transfer efficiency, ion trapping
      efficiency, and preamplifier detection limit. This work aims at analyzing the
      statistical characteristics (primarily variance) in the intensities of the
      isotopic distributions, which depend on the number of ions in the cell. A
      mathematical derivation was developed based on the maximum likelihood estimation
      method, which estimates the most likely number of ions in the cell using a method
      known as nonrandom parameter estimation. The performance of the method improves
      with increase in the number of observed distributions. The method works well
      provided the spectra show isotopic resolution and is independent of the
      instrument or method used to arrive at the spectra.

PMID- 15144186
TI  - Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T
      cells using immobilized metal affinity chromatography and tandem mass
      spectrometry.
AB  - Protein tyrosine phosphorylation cascades are difficult to analyze and are
      critical for cell signaling in higher eukaryotes. Methodology for profiling
      tyrosine phosphorylation, considered herein as the assignment of multiple protein
      tyrosine phosphorylation sites in single analyses, was reported recently
      (Salomon, A. R.; Ficarro, S. B.; Brill, L. M.; Brinker, A.; Phung, Q. T.;
      Ericson, C.; Sauer, K.; Brock, A.; Horn, D. M.; Schultz, P. G.; Peters, E. C.
      Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 443-448). The technology platform
      included the use of immunoprecipitation, immobilized metal affinity
      chromatography (IMAC), liquid chromatography, and tandem mass spectrometry. In
      the present report, we show that when using complex mixtures of peptides from
      human cells, methylation improved the selectivity of IMAC for phosphopeptides and
      eliminated the acidic bias that occurred with unmethylated peptides. The IMAC
      procedure was significantly improved by desalting methylated peptides, followed
      by gradient elution of the peptides to a larger IMAC column. These improvements
      resulted in assignment of approximately 3-fold more tyrosine phosphorylation
      sites, from human cell lysates, than the previous methodology. Nearly 70 tyrosine
      phosphorylated peptides from proteins in human T cells were assigned in single
      analyses. These proteins had unknown functions or were associated with a plethora
      of fundamental cellular processes. This robust technology platform should be
      broadly applicable to profiling the dynamics of tyrosine phosphorylation.

PMID- 15144187
TI  - Solvent extraction of sr2+ and cs+ based on room-temperature ionic liquids
      containing monoaza-substituted crown ethers.
AB  - A series of N-alkyl aza-18-crown-6 ethers were synthesized and characterized by
      NMR spectroscopy and mass spectrometry. These monoaza-substituted crown ethers in
      ionic liquids were investigated as recyclable extractants for separation of
      Sr(2+) and Cs(+) from aqueous solutions. The pH-sensitive complexation capability
      of these ligands allows for a facile stripping process to be developed so that
      both macrocyclic ligands and ionic liquids can be reused. The extraction
      efficiencies and selectivities of these monoaza-substituted crown ethers for
      Na(+), K(+), Cs(+), and Sr(2+) were studied in comparison to those of
      dicyclohexano-18-crown-6 under the same conditions. The extraction selectivity
      order for dicyclohexano-18-crown-6 in the ionic liquids investigated here was
      K(+) >> Sr(2+) > Cs(+) > Na(+). The extraction selectivity order for N-alkyl aza
      18-crown-6, in which the alkyl group is varied systematically from ethyl to n
      dodecyl, was Sr(2+) >> K(+) > Cs(+) > Na(+) in 1-ethyl-3-methylimidazolium
      bis[(trifluoromethyl)sulfonyl]amide and 1-butyl-3-methylimidazolium
      bis[(trifluoromethyl)sulfonyl]amide and K(+) > Sr(2+) > Cs(+) > Na(+) in 1-hexyl
      3-methylimidazolium bis[(trifluoromethyl)sulfonyl] amide and 1-octyl-3
      methylimidazolium bis[(trifluoromethyl)sulfonyl]amide. The strong dependence of
      selectivity on the type of ionic liquid indicates an important role played by
      solvation in solvent extraction processes based on ionic liquids. The
      optimization of macrocyclic ligands and ionic liquids led to an extraction system
      that is highly selective toward Sr(2+).

PMID- 15144188
TI  - Protein-doped monolithic silica columns for capillary liquid chromatography
      prepared by the sol-gel method: applications to frontal affinity chromatography.
AB  - The development of bioaffinity chromatography columns that are based on the
      entrapment of biomolecules within the pores of sol-gel-derived monolithic silica
      is reported. Monolithic nanoflow columns are formed by mixing the protein
      compatible silica precursor diglycerylsilane with a buffered aqueous solution
      containing poly(ethylene oxide) (PEO, MW 10,000) and the protein of interest and
      then loading this mixture into a fused-silica capillary (150-250-microm i.d.).
      Spinodal decomposition of the PEO-doped sol into two distinct phases prior to the
      gelation of the silica results in a bimodal pore distribution that produces large
      macropores (>0.1 microm), to allow good flow of eluent with minimal back
      pressure, and mesopores (approximately 3-5-nm diameter) that retain a significant
      fraction of the entrapped protein. Addition of low levels of (3
      aminopropyl)triethoxysilane is shown to minimize nonselective interactions of
      analytes with the column material, resulting in a column that is able to retain
      small molecules by virtue of their interaction with the entrapped biomolecules.
      Such columns are shown to be suitable for pressure-driven liquid chromatography
      and can be operated at relatively high flow rates (up to 500 microL x min(-1)) or
      with low back pressures (<100 psi) when used at flow rates of 5-10 microL x min(
      1). The clinically relevant enzyme dihydrofolate reductase was entrapped within
      the bioaffinity columns and was used to screen mixtures of small molecules using
      frontal affinity chromatography with mass spectrometric detection. Inhibitors
      present in compound mixtures were retained via bioaffinity interactions, with the
      retention time being dependent on both the ligand concentration and the affinity
      of the ligand for the protein. The results suggest that such columns may find use
      in high-throughput screening of compound mixtures.

PMID- 15144189
TI  - Extraction of nerve agent VX from soils.
AB  - The development and optimization of a method allowing the extraction of intact
      organophosphorus chemical warfare agent O-ethyl S-(2-diisopropylaminoethyl)
      methylphosphonothiolate (VX) from several types of soils are presented here. This
      involved the selection of an appropriate buffer to bring the sample to a pH close
      to the pK(a) of VX but sufficiently low to avoid its basic hydrolysis. Buffering
      with Tris (pH 9) and subsequent extraction of the aqueous layer by a 85:15 (v/v)
      hexane/dichloromethane mixture allows rapid and sensitive flame photometric
      detection of VX at spiking levels lower than 10 microg x g(-1), even after 3
      months of aging. Extraction yields were close to 60% in complex matrixes. This
      method also allows recovery and identification of a characteristic degradation
      product of VX, bis(2-diisopropylaminoethyl) disulfide, which appears to be formed
      during the aging process. The performance of this method is far better than that
      of OPCW reference operating procedure, which does not allow extraction of
      detectable amounts of VX (spiked at 10 microg x g(-1)) in one of the soils used
      for this study.

PMID- 15144190
TI  - A test field for the second-order advantage in bilinear least-squares and
      parallel factor analyses: fluorescence determination of ciprofloxacin in human
      urine.
AB  - The analytical performances of two algorithms, the recently introduced bilinear
      least-squares (BLLS) and the popular parallel factor analysis (PARAFAC), are
      compared as regards second-order fluorescence data recorded for the determination
      of the fluoroquinolone antibiotic ciprofloxacin in human urine samples. The
      applied chemometric methodologies employ different strategies for exploiting the
      so-called second-order advantage, which allows one to obtain individual
      concentrations of calibrated analytes in the presence of any number of
      uncalibrated (urine) components. Analysis of a spiked urine test set (in the
      analyte concentration range 0-200 mg L(-1)) showed that BLLS provides results of
      slightly better quality than PARAFAC. Satisfactory results have been obtained on
      comparing the concentrations predicted for a series of real urine samples with
      those furnished by liquid chromatography. The limit of detection of the
      fluorescence-based methods is approximately 5 mg L(-1).

PMID- 15144191
TI  - In situ investigation of drug diffusion in hydrogels by the refractive index
      method.
AB  - This work describes a simple but novel analytical method for in situ monitoring
      of the diffusion process of drugs in hydrogels based on refractive index
      measurements. The diffusion process was monitored by recording the refraction of
      a laser beam passing through a triangular cell, which allows the determination of
      changes in the refractive index distribution from the deviated distance of the
      linear beam. Compared to conventional methods, this new method exhibits
      advantages such as more simplicity, lower cost, and speed. Further, the
      refractive index method permits the determination of the concentration
      distribution of solutes in the hydrogels at any time during the diffusion process
      under nondestructive circumstances. The precision was determined by successfully
      applying this new method to the diffusion of a typical antibiotic drug, cefazolin
      sodium, in agarose gels of various concentrations. By employing Fick's second
      law, the diffusion behavior was investigated and the diffusion coefficients of
      cefazolin sodium in agarose gels were therefore obtained. Amsden's physical model
      based on obstruction effect was applied to the simulation of the diffusion
      process of cefazolin sodium and turned out to fit the results quite well.

PMID- 15144193
TI  - A chemical ionization mass spectrometry method for the online analysis of organic
      aerosols.
AB  - A new technique employing chemical ionization mass spectrometry (CIMS) is
      described that allows the composition of organic particles to be determined on
      the time scale of seconds. With this Aerosol CIMS technique, particles are
      vaporized thermally at temperatures up to 480 degrees C, and the resulting vapor
      is chemically ionized and detected with a quadrupole mass spectrometer. The
      separation of the vaporization and ionization steps allows greater control and
      more flexibility for the detection of condensed phases than with other chemical
      ionization methods. Consequently, composition can be correlated to volatility,
      providing an additional dimension of information. The use of a variety of
      positive and negative reagent ions, such as H(+)(H(2)O)(2), H(+)(CH(3)OH)(2),
      NO(+), O(2)(+), O(2)(-), F(-), and SF(6)(-), offers flexibility in the detection
      sensitivity and specificity. Furthermore, the degree of fragmentation of the
      resulting ion can be controlled, providing more straightforward identification
      and quantification than with other commonly used methods, such as electron impact
      ionization. Examples are given of the detection of aerosols consisting of
      organics with various functionalities, including alkanes, alkenes, alcohols,
      aldehydes, ketones, and carboxylic acids. Applications of this technique to
      laboratory studies of atmospherically relevant aerosol reactions are discussed.

PMID- 15144192
TI  - Secondary structure analysis of proteins embedded in spherical polyelectrolyte
      brushes by FT-IR spectroscopy.
AB  - The adsorption of bovine serum albumin (BSA), bovine beta-lactoglobulin, and
      bovine pancreatic ribonuclease A onto spherical polyelectrolyte brushes (SPB) is
      reported. The SPB consist of narrowly distributed poly(styrene) core particles
      (diameter approximately 100 nm) onto which linear chains of anionic
      polyelectrolytes are grafted. The polyelectrolyte shell consists of either the
      weak polyelectrolyte poly(acrylic acid) or the strong polyacid
      poly(styrenesulfonate). The SPB particles are dispersed in H(2)O at room
      temperature. The secondary structure of the proteins was investigated by Fourier
      transform infrared spectroscopy in transmission mode before and during adsorption
      to these colloidal brushes. The alpha-helix and beta-sheet content of the
      proteins was nearly fully retained in the adsorbed state for all systems. Only in
      the case of BSA interacting with poly(styrenesulfonic) brushes could a slight
      loss of alpha-helix structure be observed. As the interaction of SPB and proteins
      can be controlled by the ionic strength in the buffer, additional experiments
      were performed to release the adsorbed protein. The amount of released protein
      was quantified and was found to be strongly dependent on the kind of protein and
      brush used. The secondary structure of the released proteins could be analyzed as
      well. An almost full preservation of secondary structure was found. This
      demonstrates that SPB are well-suited to immobilize proteins. The SPB can be
      charged and decharged under retention of the secondary structure of the
      biomolecules.

PMID- 15144194
TI  - Exploring the analytical potential of NMR spectroscopy in chiral anisotropic
      media for the study of the natural abundance deuterium distribution in organic
      molecules.
AB  - The deuterium/hydrogen (D/H)(i) ratio measurement by quantitative (2)H NMR
      spectroscopy is a method of choice for the analysis of kinetic isotopic effects
      associated with enzyme-catalyzed reactions during a biosynthetic pathway.
      However, the efficiency of the current isotropic (2)H-[(1)H] NMR can be limited
      by the rather small chemical shift dispersion of deuterium nuclei. In addition,
      this method does not allow the enantiotopic deuterons in prochiral molecules to
      be spectrally discriminated, hence precluding the quantification of isotopic
      fractionation on methylene prostereogenic sites. In this work, we explore another
      analytical strategy able to circumvent these disadvantages. This approach is
      based on the use of natural abundance (2)H 2D NMR experiments on solutes embedded
      in polypeptidic, chiral liquid crystalline solvent. Thus, we show that NMR in
      these oriented phases is a powerful way to separate deuterium signals on the
      basis of the quadrupolar interactions, providing a promising alternative to
      overcrowded (2)H NMR spectra obtained in liquid state. To illustrate our purpose,
      we have experimentally investigated the case of 1,1'-bis(phenylthio)hexane
      derived by cleavage from methyl linoleate of safflower. The (2)H NMR results in
      chiral liquid crystals are presented and discussed. We show, for the first time,
      that (D/H)(pro-R) and (D/H)(pro-S) can be measured at the same methylene position
      of a fatty acid chain.

PMID- 15144195
TI  - Quantitative determination of heme for forensic characterization of bacillus
      spores using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - A quantitative method was developed for the determination of heme
      (ferriprotoporphyrin IX) using matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOFMS). The method was designed for forensic
      characterization of the use of blood agar in preparation of Bacillus spores. An
      alkali wash of 0.3 M ammonium hydroxide was used to solubilize heme from spore
      samples. The wash was concentrated and analyzed by MALDI-TOFMS. Experimental
      parameters were optimized to obtain the best signal intensity, maximize signal
      reproducibility, and improve day-to-day repeatability of the measurement.
      Sinapinic acid was found to be the best matrix. A sandwich sample preparation
      protocol was determined to increase the shot-to-shot and point-to-point
      reproducibility of the measurement. Cobalt(III) protoporphyrin was used as an
      internal standard and the analyte/internal standard ratio responses from
      solutions of known concentrations were used to construct a calibration curve
      (R(2) = 0.993). Limits of detection and quantitation for heme were calculated to
      be approximately 0.4 (200 fmol) and 0.8 microM (400 fmol), respectively. Spore
      samples prepared on blood agar and nonblood agar were analyzed using the method.
      Heme was detected at a concentration of approximately 0.3 ng/mg of spore on
      samples prepared on blood agar and purified by extensive washing. Heme was not
      detected on spore samples prepared without blood.

PMID- 15144196
TI  - Atmospheric pressure photoionization. 1. General properties for LC/MS.
AB  - In this work, we describe the performance of an atmospheric pressure
      photoionization (APPI) source for sampling liquid flows. The results presented
      here primarily focus on the mechanism of direct photoionization (PI), as compared
      to the dopant mechanism of PI. Measured detection limits for direct APPI were
      comparable to atmospheric pressure chemical ionization (APCI; e.g., 1 pg for
      reserpine). The ion signal is linear up to 10 ng injected quantity, with a useful
      dynamic range exceeding 100 ng. Evidence is presented indicating that APPI
      achieves significantly better sensitivity than APCI at flow rates below 200
      microL/min, making it a useful source for capillary liquid chromatography and
      capillary electrophoresis. Results are presented indicating that APPI is less
      susceptible to ion suppression and salt buffer effects than APCI and electrospray
      ionization (ESI). The principal benefit of APPI, as compared to other ionization
      sources, is in efficiently ionizing broad classes of nonpolar compounds. Thus,
      APPI is an important complement to ESI and APCI by expanding the range and
      classes of compounds that can be analyzed. In this paper, we also discuss the
      role of direct APPI vs PI-induced APCI using dopants.

PMID- 15144198
TI  - Two-dimensional nonlinear wavelet compression of ion mobility spectra of chemical
      warfare agent simulants.
AB  - Ion mobility spectrometry (IMS) affords miniaturized hand-held devices that can
      be used for monitoring and remote measurement. Because such instruments have
      limits on storage capacity or bandwidth for wireless transmission, data
      compression is important. Furthermore, all instruments should be operated with
      the fastest possible sampling rates because a signal-to-noise gain can be
      achieved by wavelet compression. Linear wavelet compression (LWC) applied to IMS
      data may cause peak distortion when the spectra are reconstructed. Nonlinear
      wavelet compression (NLWC) precisely preserves the peak location (i.e., drift
      time), height, and shape. IMS data of three chemical warfare simulants, dimethyl
      methylphosphonate, triethyl phosphate, and dipropyleneglycol monomethyl ether,
      were collected from an Ion Track ITEMISER and a Graseby Ionics detector CAM. Two
      dimensional NLWC was used to compress the IMS data in the drift time and data
      acquisition dimensions on IMS data of chemical warfare simulants. NLWC was
      applied to achieve a compression factor of 1/128 with relative error of root-mean
      square of <0.25% in the reconstructed spectra. A method was also developed and
      evaluated for optimizing compression.

PMID- 15144197
TI  - Molecular-level description of proteins from saccharomyces cerevisiae using
      quadrupole FT hybrid mass spectrometry for top down proteomics.
AB  - For improved detection of diverse posttranslational modifications (PTMs), direct
      fragmentation of protein ions by top down mass spectrometry holds promise but has
      yet to be achieved on a large scale. Using lysate from Saccharomyces cerevisiae,
      117 gene products were identified with 100% sequence coverage revealing 26
      acetylations, 1 N-terminal dimethylation, 1 phosphorylation, 18 duplicate genes,
      and 44 proteolytic fragments. The platform for this study combined continuous
      elution gel electrophoresis, reversed-phase liquid chromatography, automated
      nanospray coupled with a quadrupole-FT hybrid mass spectrometer, and a new search
      engine for querying a custom database. The proteins identified required no manual
      validation, ranged from 5 to 39 kDa, had codon biases from 0.93 to 0.083, and
      were primarily associated with glycolysis and protein synthesis. Illustrations of
      gene-specific identifications, PTM detection and subsequent PTM localization
      (using either electron capture dissociation or known PTM data stored in a
      database) show how larger scale proteome projects incorporating top down may
      proceed in the future using commercial Q-FT instruments.

PMID- 15144200
TI  - Determination of linear alkylbenzenesulfonates and their degradation products in
      soils by liquid chromatography-electrospray-ion trap multiple-stage mass
      spectrometry.
AB  - Linear alkylbenzenesulfonates (LAS) (C(10)-C(13)) and their degradation products,
      sulfophenyl carboxylate compounds (SPCs) (C(2)-C(6), C(8), C(11)), have been
      extracted from soil samples with methanol, isolated, concentrated by solid-phase
      extraction, and determined by liquid chromatography/negative ion electrospray
      quadrupole ion-trap tandem mass spectrometry (MS(n)). The ion fragmentation
      processes and pathways were studied in detail by MS, MS(2), and MS(3). Upon
      collision-induced dissociation, the deprotonated molecules of LASs render the
      ethylene-substituted benzenesulfonate ion (m/z 183), the fragmentation of which
      gave the intense signal at m/z 119, corresponding to the ethylene-substituted
      phenoxide ion formed by the loss of sulfur dioxide. The fragmentation pattern of
      SPCs shows that, for the analytes of large carbon atom chains (>5C), the neutral
      loss of water is favored whereas for those of short carbon atoms chain, the loss
      of carbon dioxide is more frequent. Multiple reaction monitoring using isolation
      only for MS and using isolation and fragmentation for MS(2) and MS(3) were used
      to identify and quantify each compound. The three MS modes have been validated in
      terms of sensitivity, selectivity, and precision, showing that each MS stage used
      reduces sensitivity 10 times. Recoveries from soil were higher than 65% at LOQ
      level for all the analytes tested, except for C(2)-C(4) SPCs by any MS mode, with
      relative standard deviation lower than 19%. The utility of the method is
      demonstrated by successfully quantifying real samples treated with these
      products. Quantification limits for the methodology developed in this work ranged
      from 0.5 to 50 microg kg(-1) by MS, from 2 to 400 microg kg(-1) by MS(2), and
      from 20 to 4000 microg kg(-1) by MS(3). Concentration levels of LASs and SPCs
      ranging from 0.1 to 15 mg kg(-1)-were found in soil samples amended with sludges,
      thus indicating their input and persistence in the soil compartment.

PMID- 15144199
TI  - Derivatization for LC-electrospray ionization-MS: a tool for improving reversed
      phase separation and ESI responses of bases, ribosides, and intact nucleotides.
AB  - We have developed a method for analyzing polar compounds by reversed-phase LC-ESI
      MS following esterification of the analytes' free hydroxyl groups with propionyl
      or benzoyl acid anhydride. The method was applied to members of the plant hormone
      group cytokinins, which includes adenine bases, ribosides/glycosides, and
      nucleotides substituted at N-6 with an isoprenoid side chain, spanning a wide
      range of polarity. It was also used to analyze other compounds of biological
      importance, e.g., the nucleotides AMP, ADP, and ATP. The formation of more
      hydrophobic derivatives had a significant impact on two aspects of the analysis.
      The retention on a reversed-phase material was greatly increased without the use
      of any acetate/formate buffer or ion pairing reagent, and the ESI response was
      enhanced, due to the higher surface activities of the derivatives. Detection
      limits of propionylated cytokinins were in the high-attomole to low-femtomole
      range, an improvement by factors of 10-100 compared to previously reported
      figures. Using an automated SPE-based purification method, 12 endogenous
      cytokinins were quantified in extracts from 20- to 100-mg samples of leaves (from
      the plant Arabidopsis thaliana) with high accuracy and precision. Furthermore,
      the chromatographic properties of the benzoylated AMP, ADP, and ATP in the
      reversed-phase LC-MS system were much better in terms of retention, separation,
      and sensitivity than those of their underivatized counterparts, even without the
      use of any ion pairing reagent. Our data show that derivatization followed by LC
      ESI-MS is an effective strategy for analyzing low molecular weight compounds,
      enabling compounds with a wide range of polarity to be determined in a single
      injection LC-MS analysis.

PMID- 15144201
TI  - Simulation studies on the effects of mobile-phase modification on partitioning in
      liquid chromatography.
AB  - Various driving forces have been suggested to explain retention and selectivity
      in reversed-phase liquid chromatography (RPLC). To provide molecular-level
      information on the retention mechanism in RPLC, configurational-bias Monte Carlo
      simulations in the Gibbs ensemble were carried out for model systems consisting
      of three phases: an n-hexadecane retentive phase, a mobile phase with varying
      water-methanol composition, and a helium vapor phase as reference state. Liquid n
      hexadecane functions as a model of a hydrophobic stationary phase, and a wealth
      of experimental data exists for this system. Gibbs free energies for solute
      transfers from gas to retentive phase, from gas to mobile phase, and from mobile
      to retentive phase were determined for a series of short linear alkanes and
      primary alcohols. Although the magnitude of the incremental Gibbs free energy of
      transfer for a methylene segment is always larger for the gas- to retentive-phase
      transfer than the gas- to mobile-phase transfer, it is found that the
      partitioning of alkanes and alkyl tail groups is mostly affected by the changes
      in the aqueous mobile phase that occur when methanol modifiers are added. In
      contrast, the partitioning of the alcohol headgroup is sensitive to changes in
      both the n-hexadecane and the mobile phases. In particular, it is found that
      hydrogen-bonded aggregates of methanol are present in the n-hexadecane phase for
      higher methanol concentrations in the mobile phase. These aggregates strongly
      increase alcohol partitioning into the retentive phase. The simulation data
      clearly demonstrate that due to modification of the retentive-phase hydrocarbons
      by solvent components, neither the solvophobic theory of RPLC, advocated by
      Horvath and co-workers, nor the lipophilic theory of RPLC, advocated by Carr and
      co-workers, can adequately describe the separation mechanism of the hexadecane
      model system of a retentive phase studied here nor the more complex situation
      present in actual RPLC systems.

PMID- 15144202
TI  - Characterization of interlayer Cs+ in clay samples using secondary ion mass
      spectrometry with laser sample modification.
AB  - Ultraviolet laser irradiation was used to greatly enhance the secondary ion mass
      spectrometry (SIMS) detection of Cs(+) adsorbed to soil consisting of clay and
      quartz. Imaging SIMS showed that the enhancement of the Cs(+) signal was
      spatially heterogeneous: the intensity of the Cs(+) peak was increased by factors
      up to 100 for some particles but not at all for others. Analysis of standard clay
      samples exposed to Cs(+) showed a variable response to laser irradiation
      depending on the type of clay analyzed. The Cs(+) abundance was significantly
      enhanced when Cs(+)-exposed montmorillonite was irradiated and then analyzed
      using SIMS, which contrasted with the behavior of Cs(+)-exposed kaolinite, which
      displayed no Cs(+) enhancement. Exposed illitic clays displayed modest
      enhancement of Cs(+) upon laser irradiation, intermediate between that of
      kaolinite and montmorillonite. The results for Cs(+) were rationalized in terms
      of adsorption to interlayer sites within the montmorillonite, which is an
      expandable phyllosilicate. In these locations, Cs(+) was not initially detectable
      using SIMS. Upon irradiation, Cs(+) was thermally redistributed, which enabled
      detection using SIMS. Since neither the illite nor the kaolinite is an expandable
      clay, adsorption to inner-layer sites does not occur, and either modest or no
      laser enhancement of the Cs(+) signal is observed. Laser irradiation also
      produced unexpected enhancement of Ti(+) from illite and kaolinite clays that
      contained small quantities of Ti, which indicates the presence of microscopic
      titanium oxide phases in the clay materials.

PMID- 15144203
TI  - Living bacterial cell array for genotoxin monitoring.
AB  - A biosensor composed of a high-density living bacterial cell array was fabricated
      by inserting bacteria into a microwell array formed on one end of an imaging
      fiber bundle. The size of each microwell allows only one cell to occupy each
      well. In this biosensor, E. coli cells carrying a recA::gfp fusion were used as
      sensing components for genotoxin detection. Each fiber in the array has its own
      light pathway, enabling thousands of individual cell responses to be monitored
      simultaneously with both spatial and temporal resolution. The biosensor was
      capable of performing cell-based functional sensing of a genotoxin with high
      sensitivity and short incubation times (1 ng/mL mitomycin C after 90 min). Dose
      response curves for several genotoxins were obtained. The biosensors demonstrated
      an active sensing lifetime of more than 6 h and a shelf lifetime of two weeks.

PMID- 15144204
TI  - Single-drop microextraction combined with low-temperature electrothermal
      vaporization ICPMS for the determination of trace Be, Co, Pd, and Cd in
      biological samples.
AB  - A new method of single-drop microextraction combined with low-temperature
      electrothermal vaporization (LTETV)-ICPMS was proposed for the determination of
      trace Be, Co, Pd, and Cd with benzoylacetone (BZA) as both extractant and
      chemical modifier. Several factors that influence the microextraction efficiency,
      such as sample flow rate, microdrop volume, and extraction time, were
      investigated and the optimized microextraction conditions were established. Be,
      Co, Pd, and Cd in the postextraction organic phase were directly determined by
      LTETV-ICPMS with the use of BZA as chemical modifier. The chemical modification
      of BZA in LTETV-ICPMS was studied, and the factors affecting the formation of
      chelates and vaporization/transportation of chelates were investigated. Under the
      optimized conditions, the detection limits of the method were 0.12, 0.99, 1.5,
      and 0.27 pg/mL for Be, Co, Pd, and Cd, and the relative standard deviations for
      0.1 ng/mL Be, Co, Pd, and Cd were 16, 14, 14, and 11%, respectively. After 10 min
      of extraction, the enrichment factors were 160 (Be), 125 (Co), 40 (Pd), and 180
      (Cd). The proposed method was applied to the determination of trace Be, Co, Pd,
      and Cd in biological reference materials, and the determined values were in good
      agreement with the certified values.

PMID- 15144205
TI  - Seeing better through a MIST: evaluation of monoclonal recombinant antibody
      fragments on microarrays.
AB  - Automation is the key approach for genomewide and proteomewide screening of
      function and interaction. Especially for proteomics, antibody microarrays are a
      useful tool for massive parallel profiling of complex samples. To meet the
      requirements of antibody microarrays and to obtain a great variety of antibodies,
      new technologies such as phage display have partly replaced the classical
      hybridoma method. While the selection process for phage-displayed antibody
      fragments itself has been automated, the bottleneck was shifted further
      downstream to the identification of monoclonal binders obtained from the
      selections. Here, we present a new approach to reduce time, material, and waste
      to extend automation beyond the selection process by application of conventional
      microarray machinery. We were able to express recombinant antibody fragments in a
      single inoculation and expression step and subjected them without purification
      directly to an automated high-throughput screening procedure based on the
      multiple spotting technique (MIST). While obtaining comparable sensitivities to
      enzyme-linked immunosorbent assays, we minimized manual interaction steps and
      streamlined the technique to be accessible within the automated selection
      procedure.

PMID- 15144206
TI  - A mammalian genetic system to screen for small molecules capable of disrupting
      protein-protein interactions.
AB  - A mammalian two-hybrid system was developed for high-throughput screening of
      compounds that disrupt specific protein-protein interactions. The existing
      mammalian systems are unsatisfactory for drug screening due to nonregulated
      expression of interacting proteins. To construct a tightly regulated system, the
      tetracycline repressor was fused with the inhibitory KRAB domain as a suppressor.
      The binding of the suppressor to the tet operator entirely blocked expression of
      two interacting proteins. When both the inducer doxycycline and drugs were added
      to the culture, the reporter gene was either activated by interaction of the
      paired proteins with ineffective drugs or remained silent due to disruption of
      the protein interactions by the effective drugs. We demonstrate that interactions
      of the type I receptor for TGFbeta with FKBP12 and the epidermal growth factor
      receptor (EGFR) with p85 are effectively disrupted by FK506 and EGFR kinase
      inhibitor AG1478, respectively. The power of this system for drug screening was
      further demonstrated by rapid identification of inhibitors from a druglike
      library for the receptor kinases.

PMID- 15144207
TI  - Impact of ion trap tandem mass spectra variability on the identification of
      peptides.
AB  - Peptide identification based on tandem mass spectrometry and database searching
      algorithms has become one of the central technologies in proteomics. At the heart
      of this technology is the ability to reproducibly acquire high-quality tandem
      mass spectra for database interrogation. The variability in tandem mass spectra
      generation is often assumed to be minimal, and peptide identifications are
      typically based on a single tandem mass spectrum. In this paper, we characterize
      the variance of scores derived from replicate tandem mass spectra using several
      database search algorithms and demonstrate the effects of spectral variability on
      the correct identification of peptides. We show that the variance associated with
      the collection of tandem mass spectra can be substantial leading to sizable
      errors in search algorithm scores ( approximately 5-25% RSD) and ultimately
      incorrect assignments. Processing strategies are discussed to minimize the impact
      of tandem mass spectra variability on peptide identification.

PMID- 15144209
TI  - A gas chromatograph/resonant electron capture-TOF mass spectrometer for four
      dimensions of negative ion analytical information.
AB  - A prototype gas chromatograph (GC) electron monochromator (EM) reflectron time-of
      flight (TOF) mass spectrometer has been constructed and demonstrated to
      simultaneously record four-dimensional resonant electron capture (REC) mass
      spectra (m/z, ion-intensity, electron-energy, and retention time) of electron
      capturing compounds in real time. Specifically, complete REC mass spectra of all
      of the components in a mixture of perfluorocarboxylic acids and in a sample of
      pentafluorobenzyl alcohol were recorded in the GC mode. For each compound, the
      data enable one to distinguish different electronic states of the molecular ion
      and different possible decomposition pathways for each state. This new instrument
      can be used to obtain analytical information unrecognizable by any other mass
      spectrometric technique from the isomeric species of a variety of electron
      capturing structures.

PMID- 15144208
TI  - 2,5-Dihydroxybenzoic acid butylamine and other ionic liquid matrixes for enhanced
      MALDI-MS analysis of biomolecules.
AB  - The performance of the new ionic liquid MALDI-MS matrix 2,5-dihydroxybenzoic acid
      butylamine (DHBB) was assessed and compared to results obtained with the ionic
      liquid MALDI-MS matrixes alpha-cyano-4-hydroxycinnamic acid butylamine (CHCAB),
      3,5-dimethoxycinnamic acid triethylamine (SinTri), and the frequently used solid
      MALDI matrixes 2,5-dihydroxybenzoic acid (DHB) and alpha-cyano-4-hydroxycinnamic
      acid (CHCA). The vacuum-stable, liquid consistency of ionic liquid matrix sample
      preparations considerably enhanced MALDI-MS analysis in terms of shot-to-shot
      reproducibility. Consequently, relative standard deviations serving as a measure
      for reproducibility of intensity-values acquired from 90 different spots on one
      MALDI-MS preparation were approximately one-half as high when solid DHB was
      replaced by the ionic liquid DHBB and eight times lower after exchange of solid
      CHCA by ionic liquid CHCAB. Interestingly, the ionic liquid MALDI matrix DHBB
      conserved the broad applicability of its solid analogue DHB, reduced MALDI
      induced fragmentation of monosialylated glycans and gangliosides, and was the
      superior ionic liquid matrix for MALDI-MS analysis of oligosaccharides and
      polymers, such as poly(ethylene glycol). It also worked well with
      glycoconjugates, peptides, and proteins; however, the tendency of DHBB to form
      multiple alkali adduct ions with peptides and proteins made CHCAB the ionic
      liquid matrix of choice for peptides. SinTri was the best ionic liquid matrix for
      proteins of high molecular weight, such as IgG. Furthermore, it was demonstrated
      for the first time that solvent properties and MALDI matrix properties of ionic
      liquids, such as DHBB, can be combined to enable fast, direct screening of an
      enzymatic reaction. This was proven by the desialylation of sialylactose with
      sialidase from Clostridium perfringens in the presence of diluted aqueous DHBB
      and subsequent direct MALDI-MS analysis of the reaction mixture.

PMID- 15144210
TI  - Suppression of alpha-cyano-4-hydroxycinnamic acid matrix clusters and reduction
      of chemical noise in MALDI-TOF mass spectrometry.
AB  - Progress in high-throughput MALDI-TOFMS analysis, especially in proteome
      applications, requires development of practical and efficient procedures for the
      preparation of proteins and peptides in a form suitable for high acquisition
      rates. These methods should improve successful identification of peptides, which
      depends on the signal intensity and the absence of interfering signals.
      Contamination of MALDI samples with alkali salts results in reduced MALDI peptide
      sensitivity and causes matrix cluster formation (widely reported for CHCA matrix)
      observed as signals dominating in the range below m/z 1200 in MALDI spectra. One
      way to remove these background signals, especially for concentrations of peptides
      lower than 10 fmol/microL, is to wash matrix/sample spots after peptide
      cocrystallization on the MALDI plate with deionized water prior to analysis. This
      method takes advantage of the low water solubility of the CHCA compared to its
      alkali salts. We report here that the application of some ammonium salt
      solutions, such as citrates and phosphates, instead of deionized water greatly
      improves the efficiency of this washing approach. Another way to reduce matrix
      cluster formation is to add ammonium salts as a part of the MALDI matrix. The
      best results were obtained with monoammonium phosphate, which successfully
      suppressed matrix clusters and improved sensitivity. Combining both of these
      approaches-the addition of ammonium salts in the CHCA matrix followed by one
      postcrystallization washing step with ammonium buffer-provided a substantial (
      approximately 3-5-fold) improvement in the sensitivity of MALDI-MS detection
      compared to unwashed sample spots. This sample preparation method resulted in
      improved spectral quality and was essential for successful database searching for
      subnanomolar concentrations of protein digests.

PMID- 15144212
TI  - Use of polymeric indicator for electrochemical DNA sensors: poly(4-vinylpyridine)
      derivative bearing [Os(5,6-dimethyl-1,10-phenanthroline)2Cl]2+.
AB  - A poly(4-vinylpyridine) (PVP) derivative bearing redox-active osmium complexes,
      PVP-[Os(5,6-dmphen)(2)Cl](2+) (5,6-dmphen = 5,6-dimethyl-1,10-phenanthroline),
      was employed as a hybridization indicator for electrochemical DNA sensors. PVP
      [Os(5,6-dmphen)(2)Cl](2+) exhibited approximately 1000 times higher sensitivity
      than the corresponding monomeric analogue, [Os(5,6-dmphen)(3)](2+), in DNA
      determination due to polymeric effects. The detection limit of the present sensor
      was approximately 0.5 amol. Another merit of the polymeric indicator is that the
      redox potential was found to be +360 mV (vs Ag/AgCl), which is significantly
      lower than that reported for the monomeric analogue (+672 mV). The polymeric
      indicator was applicable to the discrimination of single- and double-base
      mismatched DNAs from fully matched target DNA. The polymeric indicator can be
      removed from the electrode surface by rinsing the electrode in a high-temperature
      buffer for 6 min, and thus, the polymeric indicator-based DNA sensor can be used
      repeatedly.

PMID- 15144211
TI  - Microflow NMR: concepts and capabilities.
AB  - The principles and parameters to consider when choosing an NMR probe for analysis
      of a volume- or mass-limited sample are identified and discussed. In particular,
      a capillary-based microflow probe is described which has a mass sensitivity
      comparable to cryoprobes (observe volume approximately 40 microL), but with
      several distinct advantages. The microflow probe has a flowcell volume of 5
      microL and an observe volume of 1.5 microL and is equipped with proton and carbon
      observe channels, deuterium lock, and z-gradient capability. The entire flow path
      is fused silica; inlet and outlet capillary inner diameters are 50 microm to
      minimize sample dispersion, making it well-suited to volume-limited samples. An
      injected sample of 1 nmol of sucrose (0.34 microg in 3 microL, 0.33 mM; MW = 342
      g/mol) yields a 1D proton spectrum in 10 min on a spectrometer of 500 MHz or
      higher. In another example, 15 microg of sucrose (in 3 microL; 15 mM, 45 nmol) is
      injected and parked in the probe to yield a heteronuclear multiple-quantum
      coherence (HMQC) spectrum in less than 15 h. The natural product muristerone A
      (75 microg in 3 microL, 50 mM, 150 nmol; MW = 497 g/mol) was delivered to the
      flow cell, and a gradient correlation spectroscopy spectrum was acquired in 7
      min, a gradient HMQC in 4 h, and a gradient heteronuclear multiple-bond
      correlation in 11 h. Four basic modes of sample injection into the probe vary in
      degree of user intervention, speed, solvent consumption, and sample delivery
      efficiency. Manual, manual-assisted (employing a micropump), automated (using an
      autosampler), and capillary HPLC modes of operation are described.

PMID- 15144214
TI  - Geometric trajectory analysis of metabolic responses to toxicity can define
      treatment specific profiles.
AB  - Metabonomics can be viewed as the process of defining multivariate metabolic
      trajectories that describe the systemic response of organisms to physiological
      perturbations through time. We have explored the hypothesis that the homothetic
      geometry of a metabolic trajectory, i.e., the metabolic response irrespective of
      baseline values and overall magnitude, defines the mode of response of the
      organism to treatment and is hence the key property when considering the
      similarity between two sets of measurements. A modeling strategy to test for
      homothetic geometry, called scaled-to-maximum, aligned, and reduced trajectories
      (SMART) analysis, is presented that together with principal components analysis
      (PCA) facilitates the visualization of multivariate response similarity and hence
      the interpretation of metabonomic data. Several examples of the utility of this
      approach from toxicological studies are presented as follows: interlaboratory
      variation in hydrazine response, CCl(4) dose-response relationships, and
      interspecies comparison of bromobenzene toxicity. In each case, the homothetic
      trajectories hypothesis is shown to be an important concept for the successful
      multivariate modeling and interpretation of systemic metabolic change. Overall,
      geometric trajectory analysis based on a homothetic modeling strategy like SMART
      facilitates the amalgamation and comparison of metabonomic data sets and can
      improve the accuracy and precision of classification models based on metabolic
      profile data. Because interlaboratory variation, normal physiological variation,
      dose-response relationships, and interspecies differences are also key areas of
      concern in genomic and proteomic as well as metabonomic studies, the methods
      presented here may also have an impact on many other multilaboratory efforts to
      produce screenable "-omics" databases useful for gauging toxicity in safety
      assessment and drug discovery.

PMID- 15144216
TI  - Succinylacetone oxidation by oxygen/peroxynitrite: a possible source of reactive
      intermediates in hereditary tyrosinemia type I.
AB  - Hereditary tyrosinemia type I (HT1) is an inborn metabolic error characterized by
      hepatorenal dysfunction. Affected patients excrete large quantities of
      succinylacetone (SA), a tyrosine catabolite believed to be involved in the
      pathogenesis of HT1. A growing body of evidence relates the oxidative stress
      observed in metabolic disorders to free radicals generated from accumulated
      metabolites. In this context, oxidation of SA by peroxynitrite or cytochrome c
      yielding reactive intermediates and products was investigated here. Both
      peroxynitrite and cytochrome c were able to initiate oxygen consumption by SA,
      which was followed by polarimetric and chemiluminescence measurements. The light
      emission arises from triplet carbonyls formed by the thermolysis of dioxetane
      intermediates, as indicated by energy transfer experiments. EPR spin-trapping
      studies with 2-methyl-2-nitrosopropane revealed the intermediacy of two different
      carbon-centered radicals, one of them originating from cleavage of the triplet
      carbonyl product. The pH profiles obtained by oxygen consumption,
      chemiluminescence, and stopped-flow spectrophotometry point to the peroxynitrite
      anion as the initiator of SA aerobic oxidation. Overstoichiometric formation of
      organic acids based on added peroxynitrite confirms the occurrence of an oxygen
      dependent chain reaction, here proposed to be initiated by one electron
      abstraction from the enolic form of SA. The results obtained may help shed light
      on the role of both SA and oxidative stress in the pathogenesis of HT1.

PMID- 15144215
TI  - Identification of O2-substituted pyrimidine adducts formed in reactions of 4
      (acetoxymethylnitrosamino)- 1-(3-pyridyl)-1-butanone and 4-(acetoxymethylnitros-
      amino)-1-(3-pyridyl)-1-butanol with DNA.
AB  - Metabolic hydroxylation of the methyl group of the tobacco specific carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) results in the formation of
      intermediates that can alkylate DNA. Similarly, metabolic hydroxylation of the 2'
      position of the tobacco specific carcinogen N'-nitrosonornicotine gives DNA
      alkylating intermediates. The resulting pyridyloxobutyl and pyridylhydroxybutyl
      adducts with dGuo have been characterized, but there are no reports of pyrimidine
      adducts. Therefore, in this study, we investigated the reactions of 4
      (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKCH(2)OAc) and 4
      (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol (NNALCH(2)OAc) with DNA, dCyd,
      and dThd. NNKCH(2)OAc and NNALCH(2)OAc are stable precursors to the products
      formed upon metabolic methyl hydroxylation of NNK and NNAL. Analysis by LC-ESI
      SIM of enzyme hydrolysates of DNA that had been allowed to react with NNKCH(2)OAc
      and NNALCH(2)OAc demonstrated the presence of major adducts with dCyd and dThd.
      The dCyd adducts were thermally unstable, releasing 4-HPB (18) or 4-hydroxy-1-(3
      pyridyl)-1-butanol (25) upon treatment at 100 degrees C, pH 7.0. The dThd adducts
      were stable under these conditions. The dCyd adduct of NNALCH(2)OAc was
      characterized by its MS and UV and by conversion upon neutral thermal hydrolysis
      to the corresponding Cyt adduct, which was identified by MS, UV, and NMR. The
      dCyd and Cyt adducts of NNKCH(2)OAc were similarly characterized. The dThd adduct
      of NNKCH(2)OAc was identified by MS, UV, and NMR. Treatment of this adduct with
      NaBH(4) gave material, which was identical to that produced upon reaction of
      NNALCH(2)OAc with DNA or dThd. These data demonstrate that the major pyrimidine
      adducts formed in the reactions of NNKCH(2)OAc with DNA are O(2)[4-(3-pyridyl)-4
      oxobut-1-yl]dCyd (26) and O(2)[4-(3-pyridyl)-4-oxobut-1-yl]dThd (30) while those
      produced from NNALCH(2)OAc are O(2)[4-(3-pyridyl)-4-hydroxybut-1-yl]dCyd (28)
      andO(2)[4-(3-pyridyl)-4-hydroxybut-1-yl]dThd (31). Levels of these pyrimidine
      adducts of NNKCH(2)OAc in DNA were substantially greater than those of the dGuo
      adducts of NNKCH(2)OAc, based on MS peak area. Furthermore, 26 was identified as
      a major 4-HPB releasing adduct of NNKCH(2)OAc. These results suggest that
      pyrimidine adducts of tobacco specific nitrosamines may be important contributors
      to their mutagenic and carcinogenic activity.

PMID- 15144217
TI  - A proteomic investigation of drug-induced steatosis in rat liver.
AB  - A significant problem faced by pharmaceutical companies today is the failure of
      lead compounds in the later stages of development due to unexpected toxicities.
      We have used two-dimensional differential in-gel electrophoresis and mass
      spectrometry to identify a proteomic signature associated with hepatocellular
      steatosis in rats after dosing with a compound in preclinical development. Liver
      toxicity was monitored over a 5 day dosing regime using blood biochemical
      parameter measurements and histopathological analysis. As early as 6 h
      postdosing, livers showed hepatocellular vacuolation, which increased in extent
      and severity over the course of the study. Alterations in plasma glucose, alanine
      aminotransferase, and aspartate aminotransferase were not detected until the
      third day of dosing and changed in magnitude up to the final day. The proteomic
      changes were observed at the earliest time point, and many of these could be
      associated with known toxicological mechanisms involved in liver steatosis. This
      included up-regulation of pyruvate dehydrogenase, phenylalanine hydroxylase, and
      2-oxoisovalerate dehydrogenase, which are involved in acetyl-CoA production, and
      down-regulation of sulfite oxidase, which could play a role in triglyceride
      accumulation. In addition, down-regulation of the chaperone-like protein, glucose
      regulated protein 78, was consistent with the decreased expression of the
      secretory proteins serum paraoxonase, serum albumin, and peroxiredoxin IV. The
      correlation of these protein changes with the clinical and histological data and
      their occurrence before the onset of the biochemical changes suggest that they
      could serve as predictive biomarkers of compounds with a propensity to induce
      liver steatosis.

PMID- 15144218
TI  - Iso[7]LGD2-protein adducts are abundant in vivo and free radical-induced
      oxidation of an arachidonyl phospholipid generates this D series isolevuglandin
      in vitro.
AB  - Isolevuglandins (isoLGs) are a family of gamma-ketoaldehydes, aka isoketals or
      neuroketals, that are generated by free radical-induced oxidation of
      polyunsaturated fatty acid-containing lipids. Because of their high reactivity
      toward epsilon-amino groups of lysyl residues, isoLGs are found as protein
      adducts in vivo. Plasma levels of isoLG-derived protein modifications are orders
      of magnitude higher than levels of the corresponding isoprostane. This suggests
      that while isoprostanes are rapidly cleared from the circulation, isoLG-protein
      adducts accumulate over the lifetime of the protein, which can be weeks, and this
      may provide a dosimeter for oxidant stress. We now confirm the postulated
      formation of the first D series isoLG, iso[7]LGD(2), by free radical-induced
      oxidation of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine in vitro. We
      also show that iso[7]LGD(2)-protein adduct levels in blood are the highest known
      for an isoLG-derived epitope. They average 30-fold higher than isoLGE(2)-protein
      and 3-fold higher than iso[4]LGE(2)-protein levels. Similarly, iso[7]LGD(2)
      derived epitope levels in oxidized low density lipoprotein are 20 times higher
      than isoLGE(2)-protein and five times higher than iso[4]LGE(2)-protein levels.
      Previous studies showed that plasma levels of protein-bound E series isoLGs,
      i.e., isoLGE(2) and iso[4]LGE(2), are elevated in individuals with
      atherosclerosis as compared with age-matched controls. Plasma iso[7]LGD(2)
      protein immunoreactivity in individuals with atherosclerosis averages 8.5 +/- 3.1
      nmol/mL, significantly higher (P = 0.01) than the 3.5 +/- 0.1 nmol/mL in healthy
      controls. Plasma levels of iso[7]LGD(2)-protein adducts are strongly correlated
      with iso[4]LGE(2)- (r = 0.933) and isoLGE(2)-protein adducts (r = 0.877). This
      supports the hypothesis that isoLGs are generated in vivo by parallel competing
      radical-induced pathways.

PMID- 15144219
TI  - Metabolism is required for the expression of ecstasy-induced cardiotoxicity in
      vitro.
AB  - Cardiovascular complications associated with 3,4-methylenedioxymethamphetamine
      (MDMA, ecstasy) abuse have increasingly been reported. The indirect effect of
      MDMA mediated by a sustained high level of circulating biogenic amines may
      contribute to the cardiotoxic effects, but other factors, like the direct toxic
      effects of MDMA and its metabolites in cardiac cells, remain to be investigated.
      Thus, the objective of the present in vitro study was to evaluate the potential
      cardiotoxic effects of MDMA and its major metabolites 3,4
      methylenedioxyamphetamine (MDA), N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA),
      and alpha-methyldopamine (alpha-MeDA) using freshly isolated adult rat
      cardiomyocytes. The cell suspensions were incubated with these compounds in the
      final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 4 h. alpha-MeDA, N-Me
      alpha-MeDA, and their respective aminochromes (oxidation products) were
      quantified in cell suspensions by HPLC-DAD. The toxic effects were evaluated at
      hourly intervals for 4 h by measuring the percentage of cells with normal
      morphology, glutathione (GSH), and glutathione disulfide (GSSG); intracellular
      Ca(2+), ATP, and ADP; and the cellular activities of glutathione peroxidase,
      glutathione reductase, and glutathione-S-transferase. No toxic effects were found
      after exposure of rat cardiomyocytes to MDMA or MDA at any of the tested
      concentrations for 4 h. In contrast, their catechol metabolites N-Me-alpha-MeDA
      and alpha-MeDA induced significant toxicity in rat cardiomyocytes. The toxic
      effects were characterized by a loss of normal cell morphology, which was
      preceded by a loss of GSH homeostasis due to conjugation of GSH with N-Me-alpha
      MeDA and alpha-MeDA, sustained increase of intracellular Ca(2+) levels, ATP
      depletion, and decreases in the antioxidant enzyme activities. The oxidation of N
      Me-alpha-MeDA and alpha-MeDA into the toxic compounds N-methyl-alpha
      methyldopaminochrome and alpha-methyldopaminochrome, respectively, was also
      verified in cell suspensions incubated with these MDMA metabolites. The results
      obtained in this study provide evidence that the metabolism of MDMA into N-Me
      alpha-MeDA and alpha-MeDA is required for the expression of MDMA-induced
      cardiotoxicity in vitro, being N-Me-alpha-MeDA the most toxic of the studied
      metabolites.

PMID- 15144220
TI  - Human flavin-containing monooxygenase form 2 S-oxygenation: sulfenic acid
      formation from thioureas and oxidation of glutathione.
AB  - Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming
      reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with
      GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S
      oxygenation is an example of FMO-dependent bioactivation of a xenobiotic.
      Functional FMO2 is expressed in the lung of 26% of individuals of African descent
      and 5% of Hispanics but not in Caucasians or Asians. We have previously
      demonstrated that human FMO2.1 protein expressed in Sf9 microsomes has high
      activity toward a series of thioureas that are known or suspected lung toxicants
      including thiourea, 1-phenylthiourea, and ethylenethiourea. We now show by HPLC
      and LC-MS that 1-phenylthiourea and alpha-naphthylthiourea are converted to their
      sulfenic acids. GSH in the incubations at concentrations of 0.5-1.0 mM completely
      eliminated the sulfenic acid with resultant production of GSSG. These results
      indicate that individuals with the FMO21 allele may be at enhanced risk of
      pulmonary damage upon exposure to thioureas.

PMID- 15144221
TI  - Structural characterization of diastereoisomeric ethano adducts derived from the
      reaction of 2'-deoxyguanosine with trans,trans-2,4-decadienal.
AB  - Background levels of exocyclic DNA adducts have been detected in rodent and human
      tissues. Several studies have focused on bifunctional electrophiles generated
      from lipid peroxidation as one of the endogenous sources of these lesions. We
      have previously shown that the reaction of 2'-deoxyguanosine (dGuo) with
      trans,trans-2,4-decadienal (DDE), a highly cytotoxic aldehyde generated as a
      product of lipid peroxidation in cell membranes, results in the formation of a
      number of different base derivatives. Three of these derivatives have been fully
      characterized as 1,N(2)-etheno-2'-deoxyguanosine adducts. In the present work,
      four additional adducts, designated A3-A6, were isolated from in vitro reactions
      by reversed-phase HPLC and fully characterized on the basis of spectroscopic
      measurements. Adducts A3-A6 are four diastereoisomeric 1,N(2)-hydroxyethano-2'
      deoxyguanosine derivatives possessing a carbon side chain with a double bond and
      a hydroxyl group. The systematic name of these adducts is 6-hydroxy-3-(2'-deoxy
      beta-D-erythro-pentafuranosyl)-7-((E)-1-hydroxy-oct-2-enyl)-3,5,6,7-tetrahydro
      imidazo[1,2-a]purin-9-one. The proposed reaction mechanism yielding adducts A3-A6
      involves DDE epoxidation at C2, followed by nucleophilic addition of the
      exocyclic amino group of dGuo to the C1 of the aldehyde and cyclization, via
      nucleophilic attack, on the C2 epoxy group by N-1. The formation of adducts A1-A6
      has been investigated in acidic, neutral, and basic pH in the presence of
      H(2)O(2) or tert-butyl hydroperoxide. Neutral conditions, in the presence of
      H(2)O(2), have favored the formation of adducts A1 and A2, with minor amounts of
      A3-A6, which were prevalent under basic conditions. These data indicate that DDE
      can modify DNA bases through different oxidative pathways involving its two
      double bonds. It is important to structurally characterize DNA base derivatives
      induced by alpha,beta-unsaturated aldehydes so that the genotoxic risks
      associated with the lipid peroxidation process can be assessed.

PMID- 15144223
TI  - Enzymes involved in the metabolism of the carcinogen 2-nitroanisole: evidence for
      its oxidative detoxication by human cytochromes P450.
AB  - 2-Nitroanisole (2-NA) is an important industrial pollutant and a potent
      carcinogen for rodents. Determining the capability of humans to metabolize 2-NA
      and understanding which human cytochrome P450 (P450) enzymes are involved in its
      activation and/or detoxification are important to assess an individual's
      susceptibility to this environmental carcinogen. We compared the ability of
      hepatic microsomal samples from different species including human to metabolize 2
      NA. Comparison between experimental animals and human P450 enzymes is essential
      for the extrapolation of animal carcinogenicity data to assess human health risk.
      Human hepatic microsomes generated a pattern of 2-NA metabolites, reproducing
      that formed by hepatic microsomes of rats and rabbits. An O-demethylated
      metabolite of 2-NA (2-nitrophenol) and two ring-oxidized derivatives of this
      metabolite (2,6-dihydroxynitrobenzene and 2,X-dihydroxynitrobenzene) were
      produced. No nitroreductive metabolism leading to the formation of o-anisidine
      was evident with hepatic microsomes of any species. Likewise, no DNA binding of 2
      NA metabolite(s) measured with either tritium-labeled 2-NA or the (32)P
      postlabeling technique was detectable in microsomes. Therefore, hepatic
      microsomal P450 enzymes participate in the detoxication reactions of this
      environmental carcinogen. Using hepatic microsomes of rabbits pretreated with
      specific P450 inducers, microsomes from Baculovirus transfected insect cells
      expressing recombinant human P450 enzymes, purified P450 enzymes, and selective
      P450 inhibitors, we found that human recombinant P450 2E1, 1A1, and 2B6, as well
      as orthologous rodent P450 enzymes, are the most efficient enzymes metabolizing 2
      NA. The role of specific P450 enzymes in the metabolism of 2-NA in human hepatic
      microsomes was investigated by correlating specific P450-dependent reactions with
      the levels of 2-NA metabolites formed by the same microsomes and by examining the
      effects of specific inhibitors of P450 enzymes on 2-NA metabolism. On the basis
      of these studies, we attribute most of the 2-NA oxidation metabolism in human
      microsomes to P450 2E1. These results, the first report on the metabolism of 2-NA
      by human P450 enzymes, clearly demonstrate that P450 2E1 is the major human
      enzyme oxidizing this carcinogen in human liver.

PMID- 15144222
TI  - Glutathione transferase zeta-catalyzed bioactivation of dichloroacetic acid:
      reaction of glyoxylate with amino acid nucleophiles.
AB  - Dichloroacetic acid (DCA) is a drinking water contaminant, a therapeutic agent,
      and a rodent carcinogen. Glutathione transferase zeta (GSTZ1-1) catalyzes the
      biotransformation of a range of alpha-haloalkanoates and the cis-trans
      isomerization of maleylacetoacetate. GSTZ1-1 catalyzes the bioactivation of
      fluorine-lacking dihaloacetates to S-(alpha-halocarboxymethyl)glutathione, a
      reactive intermediate that covalently modifies and inactivates the enzyme or is
      hydrolyzed to glyoxylate. The purpose of this study was to examine the GSTZ1-1
      catalyzed bioactivation of DCA, including the reaction of DCA-derived glyoxylate
      with amino acid nucleophiles and the characterization of the structures and
      kinetics of adduct formation by LC/MS. The binding of [1-(14)C]DCA-derived label
      to bovine serum albumin required both GSTZ1-1 and GSH, whereas the binding to
      dialyzed rat liver cytosolic protein was increased in the presence of GSH.
      Studies with model peptides (antiflammin-2 and IL-8 inhibitor) indicated that
      glyoxylate, rather than S-(alpha-chlorocarboxymethyl)glutathione, was the
      reactive species that modified amino acid nucleophiles. Both addition (+74 Da)
      and addition-elimination (+56 Da) adducts of glyoxylic acid were observed.
      Addition adducts (+74 Da) could not be characterized completely by mass
      spectrometry, whereas addition-elimination adducts (+56 Da) were characterized as
      2-carboxy-4-imidazolidinones. 2-Carboxy-4-imidazolidinones were formed by the
      rapid equilibrium reaction of glyoxylate with the N-terminal amino group of
      antiflammin-2 to give an intermediate carbinolamine (K(eq) = 0.63 mM(-1)), which
      slowly eliminated water to give an intermediate imine (k(2) = 0.067 hour(-1)),
      which rapidly cyclized to give the 2-carboxy-4-imidazolidinone. Glucose 6
      phosphate dehydrogenase was inactivated partially by glyoxylate when reactants
      were reduced with sodium borodeuteride, which may indicate that glyoxylate reacts
      with selective lysine epsilon-amino groups. The results of the present study
      demonstrate that GSTZ1-1 catalyzes the bioactivation of DCA to the reactive
      metabolite glyoxylate. The reaction of glyoxylate with cellular macromolecules
      may be associated with the multiorgan toxicity of DCA.

PMID- 15144224
TI  - Comparative metabolism of the aza polynuclear aromatic hydrocarbon
      dibenz[a,h]acridine by recombinant human and rat cytochrome P450s.
AB  - To assess the role of human and rat cytochrome P450s in the metabolism of aza
      polynuclear aromatic hydrocarbons (aza-PAHs) and to examine the influence of
      heterocyclic nitrogen on the metabolism of these chemicals, we have investigated
      the biotransformation of dibenz[a,h]acridine (DB[a,h]ACR), an aza-PAH with two
      nonidentical bay regions, by recombinant human cytochromes P450 1A1, 1B1, and 3A4
      and rat P450 1A1. Among the three P450s, 1A1 was the most effective in
      metabolizing DB[a,h]ACR followed by 1B1 and 3A4. The major DB[a,h]ACR metabolites
      produced by human P450 1A1 and 1B1 were the dihydrodiols with a bay region double
      bond, namely, DB[a,h]ACR-3,4-diol and DB[a,h]ACR-10,11-diol (putative proximate
      carcinogen). P450 1A1 produced a higher proportion of DB[a,h]ACR-10,11-diol
      (derived from the benzo ring adjacent to the nitrogen) (44.7%) than of DB[a,h]ACR
      3,4-diol (derived from benzo ring away from the nitrogen) (23.8%). In contrast,
      1B1 produced a much greater proportion of 3,4-diol (54.7%) than of 10,11-diol
      (6.4%). These data indicate that (i) human P450 1A1 and 1B1 differ dramatically
      with respect to the regiospecific metabolism of DB[a,h]ACR, (ii) human P450 1A1
      is substantially more active than human P450 1B1 in the metabolic activation of
      the aza-PAH to its 10,11-diol, and (iii) the presence of nitrogen influences the
      relative extent to which the two benzo ring diols with a bay region double bond
      are formed by human P450s 1A1 and 1B1. In contrast to human P450s 1A1 and 1B1,
      rat P450 1A1 showed no regioselectivity in the metabolism of DB[a,h]ACR producing
      nearly equal proportions of 10,11-diol and 3,4-diol. Despite significant
      differences in their regioselectivity, human P450 1A1 and 1B1 and rat P450 1A1
      showed similar stereoselectivity in the metabolism of DB[a,h]ACR to its diols
      having a bay region double bond, producing primarily the R,R enantiomers (>94%).
      The data of these studies indicate that human and rat P450 1A1 differ in their
      regioselectivity in the metabolism of DB[a,h]ACR to its two benzo ring diols with
      a bay region double bond and consequently in their ability to metabolically
      activate the parent aza-PAH. However, human and rat P450 1A1 do not differ with
      respect to their stereoselectivity in the metabolism of DB[a,h]ACR to the diols.

PMID- 15144225
TI  - Benzo[a]pyrene regulates osteoblast proliferation through an estrogen receptor
      related cyclooxygenase-2 pathway.
AB  - Polycyclic aromatic hydrocarbons (PAHs) have been known as a kind of
      xenoestrogen. Benzo[a]pyrene, a PAH present in tobacco smoke and tar, has been
      implicated in the induction of cell proliferation as well as tumors including
      osteosarcoma. Nevertheless, the literature about the action of benzo[a]pyrene on
      the bone system is rare. It has been identified that osteoblasts owned the
      estrogen receptors and estrogen could modulate the osteoblast proliferation. In
      this study, we found that benzo[a]pyrene was capable of increasing the cell
      proliferation in cultured rat osteoblasts, human osteosarcoma cell line (MG-63),
      and estrogen sensitive human cell line (MCF-7) but not in the human estrogen
      receptor negative cell line (MDA-MB-231). This benzo[a]pyrene-induced osteoblast
      proliferation could be inhibited by the estrogen receptor antagonist ICI182780
      and tamoxifen, PD98059 [extracellular signal-regulated kinase (ERK)/mitogen
      activated protein kinase (MAPK) inhibitor], and LY294002 [phosphatidylinositol 3
      kinase (PI3K) inhibitor] but not alpha-naphthoflavone (aryl hydrocarbon receptor
      antagonist) and SB203580 (p38 MAPK inhibitor). Western blot analysis showed that
      benzo[a]pyrene could induce the phosphorylation of ERK1/2 and Akt (PI3K
      downstream effector) in osteoblasts. The proliferating cell nuclear antigen
      protein levels in nuclear fraction of osteoblasts were also increased by
      benzo[a]pyrene. Moreover, cyclooxygenase-2 (COX-2), but not COX-1, expression
      could be induced in osteoblasts under benzo[a]pyrene treatment. Its upregulation
      was associated with the induction of prostaglandin E(2) (PGE(2)). COX-2
      inhibitors NS398 and aspirin are capable of inhibiting the benzo[a]pyrene-induced
      osteoblast proliferation. These results indicate that benzo[a]pyrene may modulate
      the osteoblast proliferation through activation of COX-2 protein.

PMID- 15144227
TI  - Stereoselective metabolic activation of alpha-hydroxy-N-desmethyltamoxifen: the R
      isomer forms more DNA adducts in rat liver cells.
AB  - The antiestrogenic drug tamoxifen forms DNA adducts in rat liver through two
      genotoxic metabolites, alpha-hydroxytamoxifen and alpha-hydroxy-N
      desmethyltamoxifen. These have now each been resolved into R- and S-enantiomers.
      The work with alpha-hydroxytamoxifen was published earlier [Osborne, et al.
      (2001) Chem. Res. Toxicol. 14, 888-893]. Here, we publish results with alpha
      hydroxy-N-desmethyltamoxifen. We prepared the derivative N-ethoxycarbonyl-N
      desmethyltamoxifen-alpha-S-camphanate, separated it into two diastereoisomers,
      and hydrolyzed them to give (+)- and (-)-alpha-hydroxy-N-desmethyltamoxifen. The
      configuration of the (-)-isomer was shown to be S- by degradation of the above
      ester to a derivative of (-)-2-hydroxy-1-phenyl-1-propanone, which has already
      been shown to have S-configuration. The two enantiomers have the same chemical
      properties and were equally reactive toward DNA in vitro at pH 6. However, on
      treatment of rat hepatocytes in culture, R-(+)-alpha-hydroxy-N-desmethyltamoxifen
      gave 10 times as many DNA adducts as the S-(-)-isomer. This suggests that the R
      isomer more readily undergoes sulfate conjugation to generate a reactive
      carbocation that attacks DNA.

PMID- 15144226
TI  - Endogenously generated hydrogen peroxide is required for execution of melphalan
      induced apoptosis as well as oxidation and externalization of phosphatidylserine.
AB  - Hydrogen peroxide (H(2)O(2)) is generated endogenously during execution of both
      intrinsic as well as extrinsic apoptotic programs suggesting that it may function
      as a secondary messenger in apoptotic pathways. In the present study, we
      investigated the role of endogenously generated H(2)O(2) by using two cell lines
      HL-60 cells and its subclone, H(2)O(2) resistant HP100 cells overexpressing
      catalase (CAT). With the exception of CAT, we found no differences in the
      expression of other primary antioxidant enzymes (Cu/Zn-superoxide dismutase, Mn
      superoxide dismutase, and glutathione peroxidase) or apoptosis-related proteins
      (Bcl-2 and Bax) in HP100 cells as compared with the parental HL-60 cells.
      Production of H(2)O(2) was readily detectable as early as 1 h after melphalan
      (Mel) exposure of HL-60 cells but not HP-100 cells. Biomarkers of apoptosis, such
      as release of cytochrome c, disruption of mitochondrial transmembrane potential,
      caspase-3 activation, and chromatin condensation, became apparent much later, 3 h
      and onward after Mel treatment of HL-60 cells. The emergence of essentially all
      biomarkers of apoptosis was dramatically delayed in HP100 cells as compared with
      HL-60 cells. A relatively minor phospholipid species, phosphatidylserine (PS),
      was markedly oxidized 3 h after Mel treatment in HL-60 cells (but not in HP100
      cells) where it was significantly inhibited by exogenously added CAT. The two
      most abundant classes of membrane phospholipids, phosphatidylcholine and
      phosphatidyletanolamine, did not undergo any significant oxidation. PS oxidation
      took place 3 h after exposure of HL-60 cells to Mel and paralleled the appearance
      of cytochrome c in the cytosol. Neither cytochrome c release nor PS oxidation
      occurred in Mel-treated HP100 cells, indicating that both endogenous H(2)O(2) and
      cytochrome c were essential for selective PS oxidation detected in HL-60 cells.
      Mel-induced PS oxidation was also associated with externalization of PS on the
      surface of HL-60 cells. Given that 3-amino-1,2,4-triazole, a CAT inhibitor,
      suppressed the resistance of HP100 cells to apoptosis, production of reactive
      oxygen species, PS oxidation, and PS externalization induced by Mel, the results
      from the present study suggest that H(2)O(2) is critical for triggering the Mel
      induced apoptotic program as well as PS oxidation and externalization.

PMID- 15144228
TI  - Metabolic formation of DHP-derived DNA adducts from a representative otonecine
      type pyrrolizidine alkaloid clivorine and the extract of Ligularia hodgsonnii
      hook.
AB  - Plants that contain pyrrolizidine alkaloids (PAs) are widely distributed, and PAs
      have been shown to be genotoxic and tumorigenic in experimental animals. Our
      recent mechanistic studies indicated that riddelliine, a tumorigenic retronecine
      type PA, induced tumors via a genotoxic mechanism mediated by the formation of a
      set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived
      DNA adducts. However, it is not known if this mechanism is general to PAs of
      other types. In this study, we report that the metabolism of clivorine, a
      tumorigenic otonecine type PA, by F344 rat liver microsomes results in DHP
      formation. When incubations were conducted with clivorine in the presence of calf
      thymus DNA, eight DHP-derived DNA adducts were formed. The Ligularia hodgsonnii
      Hook plant, an antitussive traditional Chinese medicine, was found to contain
      otonecine type PAs with clivorine being predominant. DHP and DHP-derived DNA
      adducts were also obtained when microsomal incubations were conducted with
      extracts of L. hodgsonnii Hook. This is the first report that DHP-derived DNA
      adducts are formed from the metabolic activation of otonecine type PA and that
      these DHP-derived DNA adducts are potential biomarkers of PA exposure and PA
      induced tumorigenicity. These results also provide evidence that the principal
      metabolic activation pathway of clivorine leading to liver genotoxicity and
      tumorigenicity is (i) formation of the corresponding dehydropyrrolizidine
      (pyrrolic) derivative through oxidative N-demethylation of the necine base
      followed by ring closure and dehydration and (ii) binding of the pyrrolic
      metabolite to DNA leading to the DNA adduct formation and tumor initiation.

PMID- 15144229
TI  - 2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline stability and reactivity.
AB  - N-Nitrosamines and nitrosamides can initiate cancer. These studies evaluated the
      stability and reactivity of 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO
      IQ) to assess its possible role in the initiation of colon cancer by 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ). (14)C-N-NO-IQ was incubated with different
      solvents and pHs in the presence and in the absence of nucleophiles and analyzed
      by HPLC. The products identified by electrospray ionization mass spectrometry
      include 2-chloro-3-methylimidazo[4,5-f]quinoline (2-Cl-IQ), 2,2'-azo-3,3'
      dimethylimidazo[4,5-f]quinoline (AZO-IQ), 2-azido-IQ (2-N(3)-IQ), 3
      methylimidazo[4,5-f]quinoline (deamino-IQ), and IQ. A variety of organic solvents
      were tested with 0.1 N HCl. 2-Cl-IQ and IQ were formed following acidification of
      all solvents. AZO-IQ was only formed in methanol. Deamino-IQ was the major
      product formed in all of the alcohols tested, except for methanol. Under acidic
      conditions that completely convert N-NO-IQ in 5 min (acetonitrile with 0.1 N
      HCl), 62% of N-NO-IQ remains after 30 min if dimethyl sulfoxide is substituted
      for acetonitrile. N-NO-IQ was stable in the physiologic pH range of 5.5-9.0 and
      did not react with nucleophiles over a 4 h period at pH 7.4 and 37 degrees C. At
      acidic pH (pH < or =2.0) for 30 min and 37 degrees C, N-NO-IQ becomes labile
      forming electrophile(s), which combine with biologically relevant nucleophiles.
      The reaction of N-NO-IQ at pH 2.0 followed first-order kinetics (t(1/2) = 10 +/-
      2 min) and was significantly increased in 10 mM NaN(3) (t(1/2) = 2 +/- 0.1 min).
      2-N(3)-IQ was the major product observed in the latter incubation. N-NO-IQ
      binding to DNA at pH 2.0 is 100-fold more than that at pH 7.4. At pH 2.0, greater
      than 90% of the binding was inhibited by 10 mM NaN(3). Thus, N-NO-IQ forms a
      reactive electrophile(s) at acidic pH, which binds DNA. N-NO-IQ reaction products
      may depend on the pH and the hydrophobic milieu of cells or tissues.

PMID- 15144230
TI  - Monitoring outcomes of pregnancy following drug exposure: a company-based
      pregnancy registry program.
AB  - Women who discover they are pregnant after exposure to a drug and pregnant women
      who have a condition that requires continued treatment during pregnancy are told
      to balance the benefits and risks of the exposure to justify continuation of
      treatment, discontinuation of treatment or, possibly, pregnancy termination.
      However, there are limited data available to inform decision-making. The Merck
      Pregnancy Registry Program is a company-run pregnancy registry whose objective is
      to acquire and analyse information on drug exposures and pregnancy outcomes to
      better describe the safety profile of Merck products used during pregnancy.
      Information is collected from women and healthcare providers who call to report
      drug exposure during pregnancy. Prospective pregnancies are followed up to
      outcome and data are collected via questionnaires, telephone calls and a review
      of medical records. Reports are classified as prospective (information received
      prior to knowledge of pregnancy outcome) or retrospective (received after the
      outcome is known). Congenital anomaly reports are assessed for timing of
      exposure, maternal age and medical history, biological plausibility and
      concomitant medication exposures. Rates of pregnancy outcomes and birth defects
      in the prospective cohort are computed and confidence intervals are calculated to
      reflect the strength of the finding based on the sample size. Rates of pregnancy
      outcomes in the Pregnancy Registry are compared with the rates of pregnancy
      outcomes in the general US population and, if available, in subpopulations with
      the relevant disease states. The limitations of post-marketing surveillance are
      well known as voluntary reporting of individuals and healthcare professionals is
      known to be subject to various types of bias. Small sample size is another major
      limitation. However, the strength of the registry lies in its ability to gather
      pregnancy outcome reports early in the life of a product and to recognise and
      analyse unusual birth defects. Our data suggest that pregnancy registries can be
      used to review human exposure data in a systematic fashion so that useful
      information can be shared with women and their healthcare providers. The use of
      the pregnancy registry design has allowed for the collection and analysis of data
      on the effects of drug exposures on human pregnancies that have otherwise been
      difficult to obtain.

PMID- 15144232
TI  - Safety of Diastat, a rectal gel formulation of diazepam for acute seizure
      treatment.
AB  - Diazepam rectal gel (Diastat) is the only medication approved by the US FDA for
      the management of selected, refractory patients with epilepsy, on stable regimens
      of antiepilepsy drugs, who require intermittent use of diazepam to control bouts
      of increased seizure activity. An analysis of the safety of diazepam rectal gel
      reveals that this formulation has certain advantages over intravenous diazepam
      administration: most notably a very low incidence of respiratory depression, low
      potential for abuse and the opportunity for out-of-hospital use by non
      professional caregivers. Sedation is the most common adverse effect of rectal
      diazepam treatment, occurring in approximately one-quarter of patients, although
      drug-induced somnolence is difficult to distinguish from normal post-ictal
      sedation. Overdosage of diazepam rectal gel is rarely associated with serious
      clinical consequences, and overdoses of up to 330% of the maximum recommended
      dosage have been reported without any respiratory or cardiac depression. Under
      administration may be a serious safety issue because of morbidity that may result
      if seizures are not terminated. Chronic administration may cause tachyphylaxis
      and should be avoided.

PMID- 15144231
TI  - Cancer risk following growth hormone use in childhood: implications for current
      practice.
AB  - The therapeutic use of growth hormone (GH) has caused concern, as it is anabolic
      and mitogenic, and its effector hormone, insulin-like growth factor (IGF)-I is
      anti-apoptotic. As both hormones can cause proliferation of normal and malignant
      cells, the possibility that GH therapy may induce cancer, increase the risk of
      tumour recurrence in those previously treated for a malignancy, or increase the
      risk of cancer in those with a predisposition, has resulted in concerns over its
      use. There are theoretical and epidemiological reasons that suggest GH and IGF-I
      may be important in tumour formation and proliferation. Malignant tumours have
      been induced in animals exposed to supraphysiological doses of GH, whereas
      hypophysectomy appears to protect animals from carcinogen-induced neoplasms. In
      vitro, proliferation and transformation of normal haemopoetic and leukaemic cells
      occurs with supraphysiological doses of GH, but not with physiological levels.
      IGF, IGF binding proteins (IGFBP) and IGFBP proteases influence the proliferation
      of cancer cells in vitro; however, GH is probably not involved in this process.
      Epidemiological studies have suggested an association between levels of IGF-I and
      cancer, and an inverse relationship between IGFBP-3 and cancer; however, these
      associations have been inconsistent. A number of studies have been undertaken to
      determine the risk of the development of cancer in children treated with GH,
      either de novo, or the recurrence of cancer in those previously treated for a
      malignancy. Despite early concerns following a report of a cluster of cases of
      leukaemia in recipients of GH, there appears to be no increased risk for the
      development of leukaemia in those treated with GH unless there is an underlying
      predisposition. Even in children with a primary diagnosis of cancer, subsequent
      GH use does not appear to increase the risk of tumour recurrence. However, a
      recent follow-up of pituitary GH recipients has suggested an increase in
      colorectal cancer. In addition, follow-up of oncology patients has suggested an
      increase in second neoplasms in those who also received GH therapy. These studies
      emphasise the importance of continued surveillance both internationally with
      established databases and also nationally through single-centre studies.

PMID- 15144233
TI  - Prevention of anaphylactic reactions to anaesthetic drugs.
AB  - Although screening tests to prevent anaphylaxis during anaesthesia have been
      advocated, such tests are unlikely to have significant impact on reducing the
      incidence of anaphylaxis during anaesthesia. This is due to the low prevalence of
      the disease, the diversity of drugs used in anaesthesia and the incidence of
      false positive and negative tests. The suggested risk factors of allergy, i.e.
      atopy, asthma, family history, female sex, previous exposure, vasectomy, use of
      zinc protamine sulfate insulin and allergy to cosmetics, eggs, fish and non
      anaesthetic drugs are not valid. Although all have theoretical or real
      associations with anaphylaxis during anaesthesia the majority of patients with
      such a history undergo uneventful anaesthesia. Fruit allergy, anaphylaxis to
      cephalosporins and penicillin, barbiturate allergy, gelatin allergy and allergy
      to metabisulphite and eggs require consideration in avoiding particular drugs.
      The incidence of anaesthetic anaphylaxis can be reduced by avoiding latex
      exposure in patients with spina bifida or latex allergy, and preventing second
      reactions in patients with a history of anaphylaxis, or major undiagnosed or
      undocumented adverse events during anaesthesia. Determining the cause of an
      adverse event and the drug responsible, and adequately communicating those
      findings can reduce second reactions. Avoiding neuromuscular blocking drugs
      (NMBDs) in patients who have reacted to an NMBD, and use of non-intravenous
      techniques should also reduce the incidence of second reactions. Desensitisation,
      and blocking with monovalent quaternary ammonium compounds may allow improved
      safety of NMBDs and pretreatment with antihistamines and corticosteroids may
      block or ameliorate the severity of reactions, but there is currently little
      evidence to support their routine use.

PMID- 15144234
TI  - Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus
      older agents.
AB  - AIM: The relative gastrointestinal toxicity of NSAIDs in normal clinical practice
      is unknown. The aim of this study was to estimate the risk of upper
      gastrointestinal bleeding associated with NSAIDs and analgesics, with special
      emphasis on those agents that have been introduced in recent years. DESIGN:
      Multicentre case-control study. PATIENTS: All incident community cases of upper
      gastrointestinal bleeding from a gastric or duodenal lesion in patients aged >18
      years of age (4309 cases). After secondary exclusions, 2813 cases and 7193
      matched controls were included in the analysis. SETTING: Eighteen hospitals in
      Spain and Italy with a total study experience of 10,734,897 person-years. MAIN
      OUTCOME MEASURE: Odds ratios of upper gastrointestinal bleeding for each drug,
      with adjustment for potential confounders. For each individual drug the reference
      category was defined as those not exposed to the drug. RESULTS: The incidence of
      upper gastrointestinal bleeding was 401.4 per million inhabitants aged >18 years.
      Thirty-eight percent of cases were attributable to NSAIDs. Individual risks for
      each NSAID were dose dependent. Ketorolac was associated with the highest risk
      estimate (24.7; 95% CI 8.0, 77.0). For newer NSAIDs, the risks were as follows:
      aceclofenac 1.4 (95% CI 0.6, 3.3), celecoxib 0.3 (95% CI 0.03, 4.1),
      dexketoprofen 4.9 (95% CI 1.7, 13.9), meloxicam 5.7 (95% CI 2.2, 15.0),
      nimesulide 3.2 (95% CI 1.9, 5.6) and rofecoxib 7.2 (95% CI 2.3, 23.0). The risk
      was significantly increased in patients with a history of peptic ulcer and/or
      upper gastrointestinal bleeding, and in those taking antiplatelet drugs.
      CONCLUSIONS: NSAID-induced upper gastrointestinal bleeding is a common cause of
      hospital admission. Apart from the patient's history of peptic ulcer, its risk
      depends on the particular drug and its dose, and on concomitant treatments. Our
      results do not confirm that greater selectivity for COX-2 confers less risk of
      upper gastrointestinal bleeding.

PMID- 15144235
TI  - Interaction of activated Cdc42-associated tyrosine kinase ACK2 with HSP90.
AB  - ACK2 (activated Cdc42-associated tyrosine kinase 2) is a specific downstream
      effector for Cdc42, a member of the Rho family of small G-proteins. ACK2
      interacts with clathrin, an endocytic vesicle coating protein, and SH3PX1, a
      sorting nexin, and is involved in clathrin-mediated endocytosis. While searching
      for proteins that interact with ACK2, we found that HSP90 (heat-shock protein 90)
      binds to ACK2. Analysis of a series of truncation mutants of ACK2 has defined the
      regions within the kinase domain of ACK2 that are required for binding to HSP90.
      The binding of HSP90 to ACK2 is blocked upon treatment with geldanamycin, an
      HSP90-specific ATPase inhibitor, and is required for the in vivo kinase activity
      of ACK2 and its association with Cdc42. Overall, our data suggest a novel
      mechanism of regulation in which HSP90 serves as a regulatory component in an
      ACK2 functional complex and plays a role in sustaining its kinase activity.

PMID- 15144236
TI  - Enhancement of correct protein folding in vivo by a non-lytic baculovirus.
AB  - The BEVS (baculovirus expression vector system) is widely used for the production
      of proteins. However, engineered proteins frequently experience the problem of
      degradation, possibly due to the lytic nature of the conventional BEVS (herein
      referred to as L-BEVS). In the present study, a non-lytic BEVS (N-BEVS) was
      established by random mutagenesis of viral genomes. At 5 days post-infection, N
      BEVS showed only 7% cell lysis, whereas L-BEVS showed 60% lysis of cells. The
      quality of protein expressed in both N- and L-BEVSs was examined further using a
      novel FRET (fluorescence resonance energy transfer)-based assay. To achieve this,
      we constructed a concatenated fusion protein comprising LUC (luciferase)
      sandwiched between EYFP (enhanced yellow fluorescent protein) and ECFP (enhanced
      cyan fluorescent protein). The distance separating the two fluorescent proteins
      in the fusion protein EYFP-LUC-ECFP (designated hereafter as the YLC construct)
      governs energy transfer between EYFP and ECFP. FRET efficiency thus reflects the
      compactness of LUC, indicating its folding status. We found more efficient FRET
      in N-BEVS compared with that obtained in L-BEVS, suggesting that more tightly
      folded LUC was produced in N-BEVS. YLC expression was also analysed by Western
      blotting, revealing significantly less protein degradation in N-BEVS than in L
      BEVS, in which extensive degradation was observed. This FRET-based in vivo
      folding technology showed that YLC produced in N-BEVS is more compact,
      correlating with improved resistance to degradation. N-BEVS is thus a convenient
      alternative for L-BEVS for the production of proteins vulnerable to degradation
      using baculoviruses.

PMID- 15144237
TI  - G-protein-coupled receptor regulation of P2X1 receptors does not involve direct
      channel phosphorylation.
AB  - P2X1 receptors for ATP are ligand-gated cation channels, which mediate smooth
      muscle contraction, contribute to blood clotting and are co-expressed with a
      range of GPCRs (G-protein-coupled receptors). Stimulation of Galpha(q)-coupled
      mGluR1alpha (metabotropic glutamate receptor 1alpha), P2Y1 or P2Y2 receptors co
      expressed with P2X(1) receptors in Xenopus oocytes evoked calcium-activated
      chloride currents (I(ClCa)) and potentiated subsequent P2X1-receptor-mediated
      currents by up to 250%. The mGluR1alpha-receptor-mediated effects were blocked by
      the phospholipase C inhibitor U-73122. Potentiation was mimicked by treatment
      with the phor-bol ester PMA. P2X receptors have a conserved intracellular PKC
      (protein kinase C) site; however, GPCR- and PMA-mediated potentiation was still
      observed with point mutants in which this site was disrupted. Similarly, the
      potentiation by GPCRs or PMA was unaffected by chelating the intracellular
      calcium rise with BAPTA/AM [bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid
      tetrakis-(acetoxymethyl ester)] or the PKC inhibitors Ro-32-0432 and
      bisindolylmaleimide I, suggesting that the regulation does not involve a calcium
      sensitive form of PKC. However, both GPCR and PMA potentiation were blocked by
      the kinase inhibitor staurosporine. Potentiation by phorbol esters was recorded
      in HEK-293 cells expressing P2X1 receptors, and radiolabelling of phosphorylated
      proteins in these cells demonstrated that P2X1 receptors are basally
      phosphorylated and that this level of phosphorylation is unaffected by phorbol
      ester treatment. This demonstrates that P2X1 regulation does not result directly
      from phosphorylation of the channel, but more likely by a staurosporine-sensitive
      phosphorylation of an accessory protein in the P2X1 receptor complex and suggests
      that in vivo fine-tuning of P2X1 receptors by GPCRs may contribute to
      cardiovascular control and haemostasis.

PMID- 15144239
TI  - 'Failure' of early oral feeding in traditional care.

PMID- 15144238
TI  - Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria
      associated membrane) and/or mitochondria?
AB  - Recent studies by our group and others have disclosed the presence of ceramides
      in mitochondria, and the activities of ceramide synthase and reverse ceramidase
      in mitochondria have also been reported. Since a possible contamination with the
      ER (endoplasmic reticulum)-related compartment MAM (mitochondria-associated
      membrane) could not be ruled out in previous studies, we have re-investigated the
      presence of the enzymes of ceramide metabolism in mitochondria and MAM highly
      purified from rat liver. In the present paper, we show that purified mitochondria
      as well as MAM are indeed able to generate ceramide in vitro through both
      ceramide synthase or reverse ceramidase, whereas the latter enzyme activity is
      barely detectable in microsomes. Moreover, ceramide synthase activities were
      recovered in outer mitochondrial membranes as well as in inner mitochondrial
      membranes. Using radiolabelled sphingosine as a substrate, mitochondria could
      generate ceramide and phytoceramide. However, the in vitro sensitivity of
      ceramide synthase toward FB1 (fumonisin B1) in mitochondria as well as in MAM was
      found to depend upon the sphingoid base: whereas dihydrosphingosine N
      acyltransferase was inhibited by FB1 in a concentration-dependent manner, FB1
      actually activated the ceramide synthase when using sphingosine as a substrate.
      Acylation of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate,
      generating ceramide 1-phosphate, was also shown with both subcellular fractions.
      Moreover, the same difference in sensitivity towards FB1 for the ceramide
      synthase activities was seen between the two phosphorylated sphingoid bases,
      raising the possibility that distinct base-specific enzymes may be involved as
      ceramide synthases. Collectively, these results demonstrate the involvement of
      mitochondria in the metabolism of ceramides through different pathways, thereby
      supporting the hypothesis that topology of ceramide formation could determine its
      function.

PMID- 15144240
TI  - Nasogastric intubation: is it necessary?

PMID- 15144241
TI  - A culture of performance and accountability must be supported.

PMID- 15144242
TI  - Early oral feeding after colorectal resection: a randomized controlled study.
AB  - BACKGROUND: Nasogastric (NG) intubation is widely used following elective
      abdominal operations although it is associated with morbidity and discomfort. The
      present study is a randomised controlled trial on the effect of early oral
      feeding without NG decompression following elective colorectal resection for
      cancer. METHODS: One hundred patients were randomized to group A (NG catheter and
      fasting until passage of flatus, followed by liquid diet advanced to soft-solid)
      or group B (no NG tube, clear liquids the day after surgery, followed by soft
      solid food). The endpoints were: (i) morbidity; (ii) resumption of intestinal
      function; (iii) length of hospital stay; and (iv) patients' well being evaluated
      by short-form health survey [36 items] (SF-36). RESULTS: Twelve complications
      occurred in group A (50 patients) and 13 in group B (50 patients) (P = NS). Seven
      patients developed vomiting in group A as compared to 16 in group B (P < 0.05).
      Twenty per cent of patients required NG decompression in group B hence 80% did
      not need NG tubes. Resumption of intestinal function occurred after 4 days, and
      length of hospital stay was 7 days in both groups. No significant difference was
      detected between groups (P = NS) in the SF-36 score change before and after the
      operation. CONCLUSION: Patients undergoing elective colorectal resection can be
      managed without postoperative NG catheters, starting oral feeding on the first
      postoperative day. Albeit, no reduction in postoperative hospital stay or
      patients' well being could be detected, abolition of postoperative NG intubation
      with early oral feeding was a safe approach, with only 20% of patients requiring
      NG decompression because of repeated episodes of vomiting.

PMID- 15144243
TI  - Accuracy of mandatory surgeon recording of unplanned return to theatre.
AB  - BACKGROUND: Unplanned return to theatre (URTT) is a common performance indicator
      in surgery. The aim of this study is to determine the accuracy of recording URTT
      in orthopaedic surgery, and whether it is improved when recorded by the operating
      surgeon. METHODS: All orthopaedic URTT at St. George Hospital (Kogarah,
      Australia), as recorded by nursing staff, from 1 January 2001 to 31 December 2001
      were reviewed. The results were compared to a similar review for the period from
      1 June 2002 to 31 May 2003, when data was entered by the operating surgeon.
      RESULTS: In 2001, the true URTT rate was 68 out of a total of 2250 cases. Only 39
      of these were recorded as URTT (sensitivity = 57%). Of the 2182 remaining cases,
      34 were incorrectly reported as URTT (specificity = 98.4%). In the period June
      2002-May 2003, the true URTT rate was 25 out of 2119 cases. Of these, 22 were
      correctly recorded (sensitivity = 88%). Of the 2094 remaining cases, 16 were
      incorrectly recorded as URTT (specificity = 99.2%). The differences in
      sensitivity and specificity between the two periods were statistically
      significant. CONCLUSIONS: Unplanned return to theatre cases need to be reviewed
      individually to assess clinical significance. Mandatory surgeon reporting
      significantly increases the accuracy of data.

PMID- 15144245
TI  - Do elective surgery patients use the internet to look for information about their
      condition?
AB  - BACKGROUND: As 54% of Australians have access to the internet, it might be
      expected that people scheduled for surgery would look for information on it. No
      reported Australian studies have quantified internet use by patients before
      surgery. METHODS: Patients scheduled for elective surgery in two Sydney teaching
      hospitals were asked to complete self-administered questionnaires while waiting
      in preadmission clinics. Detail on sources of information consulted about their
      condition was requested. A small sample was asked about the sites visited and the
      self-reported usefulness of the information found. RESULTS: Ten per cent (95% CI:
      8.5-11.5) of 1571 patients who participated had searched the internet for
      information relating to their condition. Logistic regression showed that these
      patients were significantly more likely to be younger than 60 years (P < 0.001;
      OR: 3.28; CI: 1.99-5.4), to be employed (P < 0.001; OR: 2.27; CI: 1.52-3.4), and
      to have a higher level of education (P = 0.001; OR: 1.9; CI: 1.28-2.83). Patients
      of Hospital 1 were significantly more likely to access the internet for
      information on their condition than those at Hospital 2 (P = 0.002; OR: 1.85; CI:
      1.28-2.7). The most nominated sources of information were friends and relatives
      (20%) and books or magazines (15%). CONCLUSION: In contrast to anecdote, use of
      the internet to access information prior to elective surgery appears low. Its
      absolute use compared with other sources of information is also low. More
      traditional forms of communication appear to still pay an important role in this
      setting.

PMID- 15144247
TI  - Sentinel node biopsy in breast cancer and melanoma requires adequate self-audit.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is an evolving technique with potential
      for improving staging. Melanoma and breast cancer are the two most commonly used
      applications. The present study relates the author's validation data in both
      diseases. METHODS: Review of a prospective database. RESULTS: Between January
      2000 and December 2001 92 cases of breast cancer were offered SNB. The first 48
      had completion axillary dissection. The identification rate was 92%. There were
      28 true negative, 15 true positive and one false negative case. A mean of 2.0
      nodes were removed (range 1-4). Completion axillary dissection removed a mean of
      15.1 nodes. The following 44 cases were offered a choice of SNB alone, axillary
      dissection or a combination of techniques. Thirty-seven women chose SNB alone.
      There was one technical failure, 28 negative SNB and eight positive SNB results.
      A mean of 3.1 lymph nodes were removed (range 1-9) applying a 10% rule. At 24-36
      months follow up there have been no cases of locoregional recurrence. From
      January to December 2001 36 cases of melanoma > or =1 mm were managed with SNB.
      Twenty-eight SNB were negative and eight were positive (22%). At follow up (range
      12-24 months) there were three locoregional recurrences, but only one of these
      were in the node basin determined to be previously negative by SNB (3.5%).
      DISCUSSION: Sentinel node biopsy in breast cancer is a valid alternative to full
      axillary dissection for staging the axilla. Patients can make an informed choice
      to have SNB alone if they understand the limitations of the technique and
      possible consequences of these limitations. In melanoma SNB provides valuable
      prognostic information most melanoma patients prefer to have. Adequate self-audit
      is necessary before a patient can make an informed decision to have SNB in either
      disease.

PMID- 15144248
TI  - Morbidity associated with axillary surgery for breast cancer.
AB  - AIM: To determine the prevalence of long-term complications of axillary surgery
      for breast cancer and whether preservation of the intercostobrachial nerve (ICBN)
      reduces this morbidity. METHODS: A self-administered questionnaire was mailed to
      all patients who had undergone breast cancer and axillary surgery 2.5-6 years
      previously. The questions addressed symptoms of arm pain, numbness, weakness,
      stiffness and swelling. The operation notes were reviewed to ascertain the type
      and extent of surgery and whether the ICBN was preserved or sacrificed. RESULTS:
      One hundred and seventy of 208 (82%) questionnaires were returned completed. At
      least one symptom was reported by 130 (76.5%) of patients. Numbness was the most
      common symptom, present in 60% overall. Patients who had had the ICBN preserved
      reported significantly less numbness (37.5%vs 71.7% (P < 0.001)). Pain was
      present in 45.3% of patients and those with the ICBN preserved had significantly
      less pain (31.3%vs 58.5% (P = 0.02)). Weakness was present in 40%. Swelling was
      reported in 26.4% and stiffness in 12.2%. CONCLUSION: Axillary lymph node
      dissection for breast cancer has a high long-term morbidity. Preservation of the
      ICBN during the axillary procedure significantly reduces this morbidity.

PMID- 15144249
TI  - Early in-hospital management of burn injuries in Australia.
AB  - BACKGROUND: The accurate initial assessment and management of burn injuries
      influences subsequent clinical outcome. The purpose of the present study was to
      evaluate, over a 12-year period (1989-2001), changes in the practices of
      referring hospitals in terms of early management of patients with burn injuries
      prior to transfer to a burns unit. METHODS: The details of all consecutive
      patients over two separate 12-month periods between June 1989 to May 1990 and
      between April 2000 and March 2001 who were transferred to the Burns Unit, Concord
      Repatriation General Hospital, Sydney, were prospectively recorded and
      retrospectively reviewed. In particular, the referral procedure, the accuracy of
      the referring hospital's assessment of burn size and initial fluid resuscitation
      were compared between the two time frames. RESULTS: There were 51 patients in the
      initial 12-month period and 57 patients in the latter 12-month period. Regarding
      the transfer of the latter group of patients, the referring hospital liaised
      directly by telephone with the Burns Unit registrar or consultant significantly
      more often (77%vs 45%, respectively, P < 0.05). Similar proportions of patients
      in the two time periods received correct initial assessment of burn size (39% in
      the 1989-1990 group vs 42% in the 2000-2001 group, P = 0.76). The latter group of
      patients was significantly more likely to receive the correct choice of fluid for
      initial resuscitation at the referring hospital (98%vs 61%, respectively, P <
      0.05). CONCLUSIONS: Over this 12-year period, there has been marked improvement
      in referral practices and appropriate initial fluid resuscitation for patients
      with burn injuries. Referring hospitals' assessment of burn size has not
      improved. Possible reasons for the observed changes include: increased
      postgraduate education programmes by the Royal Australasian College of Surgeons
      and the Australian and New Zealand Burns association; the formalization of
      emergency medicine training programmes by the Australasian College of Emergency
      Medicine and increasing awareness within the medical community of the presence of
      dedicated burns units.

PMID- 15144250
TI  - Protocol-based approach to suspected appendicitis, incorporating the Alvarado
      score and outpatient antibiotics.
AB  - BACKGROUND: There is evidence that antibiotics can be used as primary treatment
      for appendicitis, however, delayed surgical treatment might still be associated
      with perforation. Most patients at risk of perforation have high Alvarado scores.
      We designed a protocol-based approach to suspected appendicitis, in which the
      Alvarado score was used to select patients for early treatment with surgery or
      outpatient antibiotics. METHODS: Patients included in the present study were
      adults and children referred to the surgical service at John Hunter Hospital
      (Newcastle, Australia) with suspected appendicitis in the 12 months from July
      2000. Treatment groups: no treatment (Alvarado score 1-4); antibiotics alone
      (Alvarado 5-7); early surgery (Alvarado 8-10). OUTCOME MEASURES: time to
      operation; duration of hospital stay; non-therapeutic operations; delayed
      treatment in association with perforation; recurrent appendicitis (for those
      treated with antibiotics). Comparison group: 142 patients managed with 'best
      clinical practice' as part of an earlier trial. RESULTS: One hundred and twenty
      two patients were enrolled. Median time to operation was 3.9 h (comparison group
      7.3 h, P = 0.014). Median length of stay was 38.5 h (comparison group 44.2 h, P =
      0.041). There were two cases of delayed treatment in association with perforation
      (2/122 = 1.6%, comparison group 2/142 = 1.4%, P = 0.88) and 10 non-therapeutic
      operations (10/122 = 8.1%, comparison group 15/142 = 10.6%, P = 0.51). Of those
      whose initial illness was treated successfully with antibiotics, 2/42 (4.8%)
      subsequently required appendicectomy. CONCLUSIONS: This protocol-based approach
      to suspected appendicitis is feasible. A prospective controlled study would be
      required to confirm potential benefits (in terms of short hospital stay) and to
      confirm that there is not an increase in adverse outcomes.

PMID- 15144252
TI  - Minimal access thyroid surgery: technique and report of the first 25 cases.
AB  - BACKGROUND: Minimal access thyroid surgery, using various techniques, is
      increasingly being reported. The present study reviews our experience with
      thyroid surgery using a lateral focused mini-incision approach, and assesses its
      safety and feasibility. METHODS: The study group comprised all patients
      undergoing minimal access thyroid surgery (MATS) during the period May 2002-May
      2003. Data were prospectively gathered, including patient demographics,
      indication for surgery, operation performed, nodule size, final pathology, and
      complications. Exclusion criteria for this procedure included: family history of
      thyroid cancer, previous neck irradiation or surgery, carcinoma on fine needle
      aspiration, presence of significant thyroiditis, multinodular goitre, and nodule
      size >3 cm. The operation was carried out through a 2.5-cm lateral incision
      placed directly over the nodule, with exposure gained by dissecting the plane
      between the sternomastoid muscle and the lateral edge of the strap muscles.
      RESULTS: Twenty-five patients underwent MATS, 22 women and three men. Nineteen
      patients underwent hemithyroidectomy, five underwent isthmectomy, and one
      underwent local nodule excision. The average measured incision size was 2.63 cm
      at the end of the procedure. The average nodule size was 2.2 cm, and the average
      thyroid lobe resected measured 4.7 cm in maximal length. Final pathology revealed
      benign nodules in 21 patients and four thyroid cancers (two follicular and two
      papillary). There was one wound infection and two patients had temporary
      recurrent laryngeal nerve neuropraxia. CONCLUSION: Minimal access thyroid surgery
      is a safe and feasible alternative to open thyroid surgery in selected cases.

PMID- 15144253
TI  - Trends in the management of severe acute pancreatitis: interventions and outcome.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) in the intensive care unit (ICU) is a
      complex and challenging problem. The aim of the present study was to identify
      trends in management of SAP patients admitted to a tertiary level ICU, and to
      relate these to changes in interventions and outcome. METHODS: Patients admitted
      to the Department of Critical Care Medicine (DCCM), Auckland Public Hospital with
      SAP from 1988 to 2001 (inclusive) were identified from the DCCM prospective
      database, and data were extracted from several sources. RESULTS: One hundred and
      twelve patients (men 69, women 43, mean age (+/-SD) 57.3 years +/- 14.3) were
      admitted with SAP to DCCM in the 13-year period. Aetiology was gallstones (42%),
      alcohol (29%), or idiopathic (29%). At admission to DCCM the median duration of
      symptoms was 7 days (range 1-100) and the mean (+/-SD) Acute Physiology and
      Chronic Health Evaluation II score was 19.9 +/- 8.2. Ninety-nine patients (88%)
      had respiratory failure and 79 (71%) had circulatory failure. The number of
      necrosectomies peaked between 1991 and 1995 (17/35 patients (49%) compared to
      4/22 (18%) prior 1991; chi(2) = 6.90, P = 0.032). Abdominal decompression,
      enteral nutrition, percutaneous tracheostomy, and the use of stents in endoscopic
      retrograde cholangiopancreatography were introduced over the study period. The
      length of stay in DCCM did not alter (median 4 days, range 1-60) but there was a
      reduction in the length of hospital stay (median 36 days to 15 days; anova= 6.16,
      P = 0.046). The overall mortality was 31% (35/112) and did not alter over the
      study period. CONCLUSIONS: SAP remains a formidable disease with a high mortality
      despite a number of changes in intensive care and surgical management.

PMID- 15144254
TI  - Single surgeon experience with bilayer polypropylene mesh repair of inguinal
      hernia.
AB  - BACKGROUND: Open mesh repair of inguinal hernia has been shown to be an effective
      and safe method of hernia repair. In search of the 'ideal' method of open mesh
      hernia repair, many different methods of mesh placement have been developed.
      Laparoscopic hernia repair is reported to be superior to open repair in terms of
      postoperative pain and rehabilitation. These improved functional outcomes could
      be the result of placement of mesh in the preperitoneal space (underlay), rather
      than the laparoscopic method per se. A bilayer polypropylene mesh implant has
      been developed that provides onlay and underlay (preperitoneal) mesh layers. The
      present study reports the singular experience of a general surgeon with this
      bilayer polypropylene mesh implant. METHODS: A retrospective audit of the first
      169 consecutive inguinal hernia repairs was conducted by mailed questionnaire and
      telephone interview. Data was collected on patient demographics, postoperative
      pain scores and complications. Patients with potential recurrences at the time of
      follow up were invited for clinical review. RESULTS: One hundred and three
      patients (71%) participated in the audit. Thirteen per cent of cases were for
      recurrent hernia. Median age was 60 years (range 21-99). Median length of follow
      up was 19 months (range 8-27). No recurrences were detected in the patients who
      underwent primary repair of inguinal hernia. CONCLUSION: Inguinal hernia repair
      with bilayer polypropylene mesh is safe and has low complication and recurrence
      rates.

PMID- 15144255
TI  - Evaluation of level 1 care facilities for vascular patients.
AB  - BACKGROUND: A surgical acute care unit (SACU) was established within our hospital
      to specifically provide level 1 care to surgical patients. We assess the impact
      that this has had on outcome in vascular patients. METHODS: All patients
      undergoing carotid endarterectomy (CEA) and elective abdominal aortic aneurysm
      repair (AAA) during the first year of SACU were included in the present study. A
      control group was compiled from patients undergoing the same two procedures in
      the year preceding the opening of the SACU. Data were collected on admission
      time, time spent in critical care, outcome and operative cancellations. RESULTS:
      During the first year of the SACU there were 28 CEA and 42 AAA repairs performed.
      In the control group there were 18 CEA and 34 AAA repairs performed. There were
      no significant differences in death rate or length of hospital stay between the
      two groups for either AAA repair or CEA. CEA patients in the study group had a
      significantly reduced level 2 stay (P < 0.001 Mann-Whitney U-test), with 71% of
      patients being admitted directly to the level 1 facility from theatre. There were
      less CEA cancelled because of critical care bed shortages among the cases (n = 0)
      compared to the control group (n = 2), although this did not reach statistical
      significance (P = 0.15 Fisher's exact test). CONCLUSIONS: Designated level 1 care
      has reduced the need for the postoperative admission of CEA patients to level 2
      care facilities. It has had no discernible impact on admission time or mortality,
      but might reduce the number of cancelled operations caused by a lack of level 2
      beds.

PMID- 15144257
TI  - Unusual locations of hydatid disease and surgical approach.
AB  - BACKGROUND: Hydatid disease is an endemic parasitic disease of the Mediterranean
      countries. Although the liver is the most commonly involved organ, the disease
      can be seen anywhere in the body. In the present study, we present our experience
      with uncommonly located hydatid disease diagnosed and treated between 1983 and
      1999 in the Sixth Surgical Department of Ankara Numune Training and Research
      Hospital, Ankara, Turkey. METHODS: Forty-nine patients with unusually located
      hydatid disease were retrospectively analysed. There were 21 men and 28 women in
      the present series. Of those, 26 patients were harbouring both hepatic and
      extrahepatic cysts, while 23 had only extrahepatic cysts. Peritoneal cavity,
      spleen, retroperitoneum, thyroid gland, anterior abdominal wall, thigh, kidney,
      presacral space and pancreas were the organs or tissues involved in the cases.
      Spleen and peritoneal cavity were the two most frequent locations in the present
      series. RESULTS: Partial or total cystectomy with or without tube drainage or
      omentopexy was the operation of choice for hydatid cyst of the peritoneal cavity.
      Splenectomy was performed for splenic hydatidosis. Mean postoperative stay was 7
      days (4-23). Three diaphragmatic and one inferior vena cava lacerations occurred
      during operations that were repaired successfully in the same sessions. No
      mortality occurred in the present series. CONCLUSION: Hydatid disease can affect
      any organ or area throughout the body and suspicion of this disease should be
      justified in patients presenting with a cystic mass in endemic areas.

PMID- 15144256
TI  - Congenital coronary artery fistulas: clinical considerations and surgical
      treatment.
AB  - BACKGROUND: Coronary artery fistulas are uncommon abnormalities that can cause
      significant cardiac morbidity. Indications for operation vary, particularly, for
      asymptomatic patients. Early surgical correction is indicated because of the high
      incidence of late symptoms and complications. METHODS: From January 1981 to
      December 2001, all 15 patients who underwent surgical management of congenital
      coronary artery fistulas at the Tri-Service General Hospital, Taipei, Taiwan,
      China were included in the present retrospective study. RESULTS: Twelve patients
      were symptomatic at the time of the diagnosis. Coronary artery fistulas involved
      the right coronary artery in five patients, left coronary artery in nine, and
      both the right and the left coronary arteries in one. Coronary artery fistula
      drained into the right ventricle in seven patients, right atrium in three,
      pulmonary artery in two, left ventricle in one, left atrium in two, and coronary
      venous sinus in one. The value of pulmonary blood flow/systemic blood flow ranged
      from 0.98 to 2.1. Six patients had associated cardiac anomalies. All patients
      received surgical correction. Nine patients received cardiopulmonary bypass
      during operation. There was zero operative mortality and operative morbidity was
      low. All patients had a stable condition and were asymptomatic during a mean
      postoperative follow-up of 13.3 years. CONCLUSIONS: Early surgical treatment for
      coronary artery fistulas is safe and effective. The risk of operative correction
      appears to be considerably less than the potential for development of serious and
      potentially fatal complications, even in asymptomatic patients.

PMID- 15144258
TI  - Waiting for elective general surgery: physical, psychological and social
      consequences.
AB  - BACKGROUND: Long surgical waiting lists are common and receive serious
      consideration. To evaluate the positive and negative effects of waiting lists,
      insight into the consequences of waiting is needed. The present study aims to
      assess what insight the current literature provides into the effects of delayed
      surgery for varicose veins, inguinal hernia in adults, gallstones, and breast
      cancer in terms of physical, psychological and social aspects. METHODS: Searches
      of Medline and Embase, for the period January 1985-September 2003, were performed
      to identify articles providing direct or indirect insight into the consequences
      of waiting for surgery for each disorder. Reference lists of retrieved reports
      were examined for relevant articles. RESULTS: Seven studies were identified with
      direct data on consequences of delay in elective surgery. Relevant indirect data
      were found in 32 reports. Results indicated that delayed varicose vein surgery or
      inguinal hernia repair involves marginal physical, psychological or social
      suffering, and that severe deterioration is unlikely. The impact of delayed
      cholecystectomy seems more profound by suffering on all three health aspects.
      Complications while waiting do occur, with a higher risk for patients with
      previous complications. Longer delays for breast cancer surgery seem to adversely
      affect prognosis, although it is unclear which interval is associated with such
      an effect. Moreover, having breast cancer undoubtedly affects psychological
      health. CONCLUSIONS: There is a remarkable paucity of studies addressing the
      consequential impact of waiting for elective surgery on patients' health for each
      of the four studied disorders. Current literature permits merely general
      estimation of this consequential impact. As specific assessment of these
      consequences is important for daily practice and for policy, further research is
      required.

PMID- 15144259
TI  - Diagnosis and management of isolated pancreatic tuberculosis: recent experience
      and literature review.
AB  - The increased reporting of tuberculosis of the pancreas is related to a worldwide
      increase in tuberculosis and an increase in emigration from countries where
      tuberculosis is endemic into countries where more sophisticated healthcare and
      radiological imaging are available. Three recent cases of pancreatic tuberculosis
      in Auckland, New Zealand, emphasize that tuberculosis should now be included in
      the differential diagnosis of a pancreatic mass. Diagnostic indicators include
      emigration from, or recent travel to, a country where tuberculosis is endemic,
      the association of a pancreatic mass with fever, the presence of abdominal pain
      and a cystic pancreatic mass in a younger male. Radiological appearances might be
      similar to a mucinous cystic neoplasm or could show a pancreatic mass with
      involvement of peripancreatic lymph nodes or a mass centred in a peripancreatic
      lymph node. When the diagnosis is suspected an human immunodeficiency virus test
      and a comprehensive screening for tuberculosis at other sites should be
      performed. If tuberculosis is unable to be diagnosed then pancreatic biopsy and
      culture is indicated. Endoscopic ultrasound with fine needle aspiration for
      cytology is likely to become the preferred technique. Most patients have an
      excellent clinical response to standard antituberculosis regimens.

PMID- 15144260
TI  - An in-vivo paradigm for the evaluation of stimulating electrodes for use with a
      visual prosthesis.
AB  - BACKGROUND: Electrical stimulation of the visual cortex with surface electrodes
      is able to elicit basic visual perceptions in blind patients. The development of
      a visual prosthesis for the blind will require an in-vivo model for the
      optimization of cortical neurostimulation with multielectrode arrays. METHODS: In
      anaesthetized cats a bilateral craniotomy was performed and the dura was removed
      to expose the cerebral cortex. A prototype stimulating electrode array was placed
      on a gyrus in one hemisphere, and the transcallosal evoked response (TER) to
      cortical stimulation by this electrode array was recorded at a homologous region
      in the contralateral hemisphere. RESULTS: The stimulating electrode array
      elicited TER of short latency (6.9 ms) in the contralateral hemisphere. Bipolar
      stimulation of adjacent electrodes on the array evoked similar TER regardless of
      the polarity of stimulation. Electrodes spread apart on the array caused higher
      amplitude TER than electrodes placed close together. Multielectrode stimulation
      evoked lower amplitude TER than bipolar stimulation. CONCLUSIONS: This
      transcallosal model of cortical neurostimulation is a useful method to evaluate
      electrode arrays and stimulation techniques in the development of a visual
      prosthesis.

PMID- 15144261
TI  - Submental intubation in complex craniomaxillofacial trauma.
AB  - The submental route for endotracheal intubation is an alternative to nasal
      intubation or tracheostomy in the surgical management of patients with complex
      craniomaxillofacial injuries. The critical indication for submental intubation is
      the requirement for intraoperative maxillomandibular fixation (MMF) in the
      presence of injuries that preclude nasal intubation and in a situation where a
      tracheostomy is not otherwise required. MMF to re-establish dental occlusion is
      essential for a normal functional result in dentate patients with fractures
      involving alveolar segments of the jaws. However, MMF precludes orotracheal
      intubation. Nasotracheal intubation is often used but is contraindicated in the
      presence of skull base fractures and will interfere with the access to certain
      fracture types. A tracheostomy has a high potential complication rate and in many
      patients, an alternative to the oral airway is not required beyond the
      perioperative period. A submental intubation has been used in 11 selected cases
      amongst 190 consecutively treated patients with craniomaxillofacial trauma over a
      3-year period. These cases have been retrospectively reviewed and there have been
      no significant complications. The indications and technique used are described.
      Submental intubation is a simple and useful technique with low morbidity in
      selected cases of craniomaxillofacial trauma and the author's clinical experience
      with this technique is described.

PMID- 15144262
TI  - Surgical fires and alcohol-based skin preparations.
AB  - Alcohol-based skin preparations are known to be flammable. Their use continues
      despite a significant level of risk. Two cases of fires resulting from ignition
      of pooled alcohol-based skin preparations are reported. Both cases were
      associated with use of electrocautery for haemostasis. The literature is reviewed
      and recommendations are made to reduce the risk of further similar occurrences.

PMID- 15144263
TI  - RE: Training of breast surgeons.

PMID- 15144264
TI  - Circumcision rate too low?

PMID- 15144265
TI  - RE: Giant Meckel's diverticulum with enterolith formation.

PMID- 15144266
TI  - Circumcision in Western Australia.

PMID- 15144267
TI  - RE: Circumcision in Western Australia.

PMID- 15144268
TI  - Circumcision in Western Australia--RACS statement.

PMID- 15144270
TI  - Laparoscopic removal of the left-sided gallbladder.

PMID- 15144269
TI  - Adrenocortical oncocytoma: benign or malignant?

PMID- 15144271
TI  - Bilateral epididymal masses with infertility.

PMID- 15144272
TI  - Gastrointestinal stromal tumour presenting as incarcerated inguinal hernia.

PMID- 15144273
TI  - Primary hydatid cyst of the axilla.

PMID- 15144274
TI  - Hemosuccus pancreaticus.

PMID- 15144275
TI  - Aorto-enteric fistula following endoluminal abdominal aortic aneurysm repair.

PMID- 15144277
TI  - A histological study of the hph-1 mouse mutant: an animal model of
      phenylketonuria and infantile hypertrophic pyloric stenosis.
AB  - AIM: To quantify the chronological sequence of changes in the morphology and
      immunoreactivity for neurotransmitters in the pylorus of an animal model of
      infantile hypertrophic pyloric stenosis and phenylketonuria. METHOD: Thirty
      specimens of pylorus from hph-1 mice and age/sex matched controls (age range: 10
      180 days) were examined using conventional histology and immunohistochemistry for
      a variety of antigens: protein gene product 9.5, a pan neuronal marker;
      vasoactive intestinal polypeptide; nitric oxide synthase two antigens coalesced
      to the same inhibitory neurons in humans; substance P, a potent excitatory
      neurotransmitter; and calcitonin gene related peptide, a neurotransmitter
      implicated in the somatic afferent innervation of the stomach. The changes in the
      morphology of the muscle layers were quantified and statistically analysed for
      each age group (10, 20, 40, 90 and 180 days). RESULTS: Between 10 and 90 days of
      age, all muscle layers of the hph-1 mice were hypertrophied, for example, 10
      days, hph-1 longitudinal muscle mean diameter = 3.4, control = 1.8; hph-1
      circular muscle width = 11.5, control = 4.7. The hph-1 mice were significantly
      smaller during this period (40 days, hph-1 weight = 10 g, control = 25 g). There
      was no change in the pattern of expression of the antigens examined within the
      hph-1 mice compared with the controls. CONCLUSION: Hph-1 mice develop a transient
      smooth muscle hypertrophy of the pylorus attended by gastric distension and
      failure to gain weight. These changes resolve as the pyloric muscle hypertrophy
      resolves.

PMID- 15144278
TI  - Some segmental features on the structure of the aortic wall of the dog.
AB  - Structural features of segmental parts of the aorta of the dog were studied by
      light microscopy (LM) and scanning electron microscopy (SEM). The variability in
      the wall architecture composition and vascular thickness of the ascending (T2-3
      level), thoracic (T7-8 level) and abdominal (L6-7 infrarenal level) segments of
      the aorta was analysed. Morphological features such as presence of intimal folds,
      pattern of the medial myoconnective components with segmental variations in the
      number of elastic lamellae, whose relative number was higher in the thoracic
      aorta (ascending and descending parts), compared with the abdominal aorta, and a
      network of connective (stromal) elements formed by elastic and collagen lamellae
      and fibres in the adventitia were observed. The results were discussed on a
      histophysiological basis, because small but significant segmental differences had
      been characterized in the aortic wall structure of the dog.

PMID- 15144279
TI  - Immunocytochemical detection of synaptophysin in enteric neurones during prenatal
      development in the rat stomach.
AB  - Summary In this study, the localization and appearance of synaptophysin
      immunoreactive (IR) nerve cells and their relationships with the developing
      gastric layers were studied by immunocytochemistry and light microscopy in the
      embryonic rat stomach. The stomachs of Wistar rat embryos aged 13-21 days were
      used. The first neuronal bodies and their processes containing synaptophysin
      immunoreactivity were observed on embryonic day 13. In contrast, synaptophysin-IR
      nerve terminals were first observed between mesenchymal cells on embryonic day
      14. These results indicate that synaptophysin is expressed in growing neurits and
      neuronal cell bodies before these neurones have established synaptic connections.
      The occurrences of mesenchymal cell condensation near synaptophysin-IR
      neuroblasts on embryonic day 15 reflect an active nerve element-specific
      mesenchymal cell induction resulting in the morphogenesis of muscle cells.
      Similarly, the appearance of glandular structures after synaptophysin-IR
      neuroblasts, on embryonic day 18, suggests that the epithelial differentiation
      may be closely related to the neuronal maturation as well as other factors.
      Finally, synaptophysin is functionally important in neuronal development and
      maturation, together with the establishment of neuroneuronal and neuromuscular
      contacts and in epithelial differentiation.

PMID- 15144280
TI  - The fine structure of the Harderian gland in the ostrich (Struthio camelus).
AB  - The Harderian gland of the ostrich (Struthio camelus) is a tubuloalveolar gland
      containing holocrine secreting epithelial cells. The gland epithelium is composed
      of two different cell types, which can be classified as type I and type II. These
      cells contain dense secretory vesicles in their cytoplasm and they are connected
      laterally with desmosomes. At the basal site of these cells, myoepithelial cells
      are present. Plasma cells are observed in the subepithelial region of the gland.
      In the interlobular trabeculae, forming the gland stroma, fibroblasts, blood
      vessels and nerve fibres are included. Another important finding in the ostrich
      Harderian gland is the presence of homogeneous material.

PMID- 15144281
TI  - Histo-anatomical studies on the accessory reproductive glands of the Anatolian
      souslik (Spermophilus xanthoprymnus) (Mammalia: Sciuridae).
AB  - In this study, the histo-anatomy of the accessory reproductive glands of the
      Anatolian souslik (Spermophilus xanthoprymnus) is investigated, using 102 males
      of the vouchers which were captured from central Anatolia and eastern
      Mediterranean regions. Averages of measurements taken from each part of the
      accessory reproductive glands were as follows: length of vesicular gland [right:
      3.96 (+/-0.48) mm; left: 3.70 (+/-0.55) mm]; prostate gland [length: 2.55 (+/
      0.38) mm; width: 2.63 (+/-0.45) mm]; length of bulbourethral gland [right: 2.32
      (+/-0.33) mm; left: 2.37 (+/-0.39) mm], and the length of the pars pelvina of the
      urethra was 12.31 (+/-0.76) mm. Histological sections showed that vesicular gland
      was composed of typically branched tubulo-alveolar glands. As the fibrous
      connective tissue that was found among alveoles in the prostate was dense and
      relatively common, only few tubulo-alveolar glands occurred. The bulbourethral
      gland (Cowper's gland) was a tubulo-alveolar gland with a large and serrated
      lumen and septa between the alveoles consisted of dense fibro-muscular fibres.

PMID- 15144283
TI  - Arterial vascularization of the uropygial glands (Gl. uropygialis) in the rock
      partridge (Alectoris graeca) living in Turkey.
AB  - This study aims to observe the morphological characteristics of the uropygial
      gland (Glandula uropygialis), specifically the arterial vascularization, in rock
      partridges (Alectoris graeca) living in Turkey. Coloured-latex-injected animals
      were dissected and the gland and related arteries were observed. Mostly, the
      fourth paired caudal segmental arteries (Aa. segmentales caudales) arising from
      the median caudal artery (A. mediana caudae) were specified as the uropygial
      gland arteries. These arteries, in turn, gave the following rami: the muscular
      ramus (Ramus muscularis) to the levator coccygeus and lateral caudal muscles, the
      lateral ramus (Ramus lateralis) to the lateral coccygeus muscle and a small
      ventro-lateral division of the caudal component of the gland, and the medial rami
      (Ramus medialis) to the dorsal surface of the gland.

PMID- 15144282
TI  - Neurosteroidogenesis in oligodendrocytes and Purkinje neurones of cerebellar
      cortex of dogs.
AB  - The cerebellum is a steroidogenic organ that expresses steroidogenic enzymes and
      produces neurosteroids. Purkinje neurones appear to be the most active
      steroidogenic cells in the cerebellar cortex. These neurones express 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD), P450 side-chain cleavage (P450scc), 17
      alpha-hydroxylase/c17, 20lyase (P450c17), P450 aromatase (P450arom) and produce
      pregnenolone, progesterone, dehydroepiandrosterone, androstenedion, oestradion
      and oestrone. Oligodendrocytes are predominantly the producer of myeline protein.
      The oligodendrocytes were identified by immunohistochemistry using a monoclonal
      antibody against myeline 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase),
      a myeline specific enzyme. In this study we have examined the distribution of 3
      beta-HSD and CNPase by immunohistochemistry using monoclonal antibody in canine
      cerebellar cortex. The localization of oligodendrocytes within the cerebellar
      cortex was determined to be close to Purkinje neurones. This result suggests that
      endogenous progesterone synthesized de novo in the Purkinje neurone can promote
      myeline protein synthesis in oligodentrocytes.

PMID- 15144284
TI  - Scanning electron microscopy of the superficial pineal gland of the 15-day-old
      rat (Rattus norvegicus).
AB  - The presence of a cortex and medulla in the superficial pineal gland has been a
      controversial point in the morphology of this structure in mammals. The published
      reports indicate contradictory data especially in rodents. In this study the
      pineal gland of 15-day-old male rats (Rattus norvegicus) were studied, using
      scanning electron microscopy, in an attempt to determine whether or not a cortex
      and medulla are apparent in the pineal gland of young rats. The superficial
      pineal gland of the 15-day-old rat exhibited both a cortex and a medulla; these
      areas exhibited different structural organizations. The cortex had a thickness of
      40-80 microm and the cells did not show a particular arrangement. The center of
      the gland was composed of a medulla, which had a width of 1000-1200 microm, and
      consisted of cells arranged in cords; its morphology was distinctly different
      from that of the cortex.

PMID- 15144285
TI  - Quantitative analysis of cells in the ganglion cell layer of the chick retina:
      developmental changes in cell density and cell size.
AB  - Changes in cell density and size in the ganglion cell layer (GCL) of the retina
      were studied in chick embryos and post-hatching chicks. The total number of cells
      in the GCL increased from 3.64 million at embryonic day 8 (E8) to the maximal
      7.85 million at E14. After E14, the number of cells decreased to 6.08 million at
      post-hatching day 1 (P1) and 4.87 million at P8. Cell density in the GCL
      decreased unevenly according to retinal regions; cell density in the presumptive
      central area (pCA) of P8-chicks decreased to approximately 45% of that in E8
      embryos. Densities of the nasal peripheral retina (NP) and temporal peripheral
      retina (TP) of P8-chicks decreased to 23 and 18% of E8-embryos, respectively.
      Differentiation of the central (44,000 cells/mm(2) in pCA) - peripheral (28,000
      cells/mm(2) in TP) gradient in cell density was formed by E8. The presumptive
      dorsal area (pDA) was shaped by E11, but became obscure with age. Although
      ganglion cell sizes were basically uniform at E8, differentiation occurred with
      the appearance of larger ganglion cells after E14. Mean size of retinal ganglion
      cells increased 2.8-fold in the pCA and 3.8-fold in the TP between E8 and P8,
      accompanying a similar scale of decreases in cell densities.

PMID- 15144286
TI  - Desmoplakin and Plakoglobin--specific markers of lymphatic vessels in the skin?
AB  - Monoclonal antibodies against Desmoplakin and Plakoglobin were tested for their
      suitability as specific markers of lymphatic vessels. The tissue samples were
      taken from horse skin in an attempt to establish the horse as a model for human
      lymphatic diseases. To obtain a clear, positive identification of blood and
      lymphatic vessels, immunohistochemical staining with antibodies against vascular
      endothelial growth factor receptor 3 (VEGFR-3) and platelet endothelial adhesion
      molecule (PECAM-1, CD31), was compared with Desmoplakin and Plakoglobin. Because
      anti-VEGFR-3 is specific for lymphatic vessels in the skin while anti-CD31 stains
      blood and lymphatic vessels as well, it can be concluded that VEGFR-3(-)/CD31(+)
      vessels are blood vessels and VEGFR-3(+)/CD31(+) vessels are lymphatic vessels.
      It was documented on serial sections that Plakoglobin stains both blood and
      lymphatic vessels. However, Desmoplakin did not stain several positively
      identified lymphatic vessels. Therefore, Desmoplakin and Plakoglobin antibodies
      are not specific markers of lymphatic vessels in the skin and the staining
      pattern is tissues and species dependent.

PMID- 15144287
TI  - Development of ileal Peyer's patches and follicle associated epithelium in bovine
      foetuses.
AB  - The development of the ileal Peyer's patches (ilPP) and follicle associated
      epithelium (FAE) was examined in 30 bovine foetuses ranging from 73 to 271 days
      of gestation by light and transmission electron microscopic methods. The first
      primordial ilPP was encountered in the foetus at 164 days of gestation The ilPP
      were found to have been formed from the aggregation of lymph follicles in the
      foetus at 227 days of gestation whereas in the foetus at 271 days of gestation
      the follicular development was observed to have been completed. While the cells
      in the FAE in the foetus at 164 days of gestation and those older were cuboidal,
      those of the foetus at 271 days of gestation were columnar. As from the foetus at
      227 days of gestation, however, the FAE was found to be composed of uniform
      lymphoepithelial cells with an increase in the number of intraepithelial
      leukocytes. In the early stages, whereas the apical surfaces of the FAE cells
      appeared shorter with microfolds, with advancing age the apical surfaces of the
      FAE cells were observed to be heterogeneous. Our results suggest that bovine ilPP
      and FAE cells are histologically and functionally mature before birth.

PMID- 15144288
TI  - Sirius red is able to selectively stain eosinophil granulocytes in bovine, ovine
      and equine cervical tissue.
AB  - The aim of the present study was to examine the suitability of sirius red
      staining for selective light microscopic demonstration of eosinophil granulocytes
      in cervical tissue of mares, cows and sheep. For this purpose, tissue was fixed
      in 4% neutral buffered formol or in Bouin's solution. Paraffin sections of 5
      microm thickness were stained with sirius red. In cows, mares and sheep a
      selective distinction of eosinophilic infiltration is successful after both
      fixation methods.

PMID- 15144289
TI  - Stereology of the liver in three species of Leontopithecus (Lesson, 1840)
      Callitrichidae--primates.
AB  - Studies on liver morphology and stereology are relevant to the comparative
      anatomical and pathological research. They also facilitate the use of non-human
      primates in basic research, which has substantially supported studies in human
      medicine. Quantitative studies of liver structures have also been more extensive
      in Old World primates and other vertebrates. Twenty-three livers of adult lion
      tamarins were studied (six Leontopithecus rosalia, seven Leontopithecus
      chrysomelas, and 10 Leontopithecus chrysopygus), dissected, and fixed in 10%
      neutral buffered formalin solution. For stereological quantification, the liver
      was regarded as consisting of parenchyma (hepatocytes) and stroma (non
      hepatocytes). The volume density (V(v)) was determined by point counting, and the
      disector method was used to obtain the numerical density of hepatocytes (N(v)).
      Hepatic stereological differences among the three species of lion tamarins were
      not statistically significant. Therefore, the pooled V(v[hepatocyte]) and
      V(v[stroma]) could be determined as 96.2 and 7.4%, respectively, and
      N(v[hepatocyte]) as 500.33 x 10(6) cm(-3). Significantly different, the values
      found for V(v[hepatocyte]) and N(v[hepatocyte]) in lion tamarins were,
      respectively, 0.09 and 2.8 times greater than those in baboons, and 0.17 and 3.8
      times greater than those in man. However, the V(v[stroma]) was 1.04 times smaller
      than that in baboons and 1.79 times smaller than that in man.

PMID- 15144290
TI  - Ethical dichotomies and methods of seeking consent.

PMID- 15144291
TI  - Anaesthetists' intentions to violate safety guidelines.
AB  - The Theory of Planned Behaviour has been used to investigate the likelihood that
      anaesthetists will routinely perform three violations of safety guidelines. The
      three violations were: failing to visit patients before surgery, failure to
      perform pre-anaesthetic equipment checks and the silencing of alarms during
      anaesthesia. These suggested violations arose from discussions with the Medical
      Defence Union. In forming the intention not to perform these violations,
      anaesthetists are most influenced by their normative beliefs about the violation,
      i.e. the opinion they believe a group of peers and other significant other people
      would hold about them performing the violation. The next most influential factor
      is their personal norms, i.e. beliefs that the individual has about whether the
      violation is really right or wrong, followed by behavioural beliefs, i.e. beliefs
      about the consequences of performing the violation, and control beliefs, i.e.
      beliefs about how much control they have over performing the violation. The
      results show that the more intense the anaesthetists' belief that the violations
      were important, the less likely they were to violate, except for the case of
      alarm silencing. This result suggests that there may be a basic lack of
      confidence in the reliability of audible alarms that undermines their utility.

PMID- 15144292
TI  - Accuracy of the Foldes-Biro equation for measurement of oxygen uptake during
      anaesthesia: a laboratory simulation.
AB  - Laboratory benchtop testing was conducted of the Biro method for measurement of
      oxygen uptake from an anaesthetic breathing system by patients during low flow
      anaesthesia. A high precision flow and gas concentration measurement system was
      employed in conjunction with a physical gas exchange simulation model to test the
      theoretical basis of the method under controlled conditions. Simulated oxygen
      uptake values between 200 and 350 ml x min(-1) were modelled. The Biro-derived
      measurement of simulated O(2) uptake significantly underestimated the target
      value (mean difference -88.5 ml x min(-1), or -31.7%). The bias was directly
      proportional to the simulated O(2) uptake. The Biro method has a systematic bias
      that cannot be explained by random measurement imprecision.

PMID- 15144294
TI  - The role of prophylactic fresh frozen plasma in decreasing blood loss and
      correcting coagulopathy in cardiac surgery. A systematic review.
AB  - Summary Fresh frozen plasma is commonly used in cardiac surgery in an attempt to
      replace clotting factors and to decrease bleeding. Despite this, there has been
      no previous review of the available literature to support this practice. The aim
      of this review was to study the effect of prophylactic peri-operative transfusion
      of fresh frozen plasma on bleeding and coagulopathy in patients undergoing
      cardiac surgery. A comprehensive literature search was performed and all
      randomised controlled trials of the use of fresh frozen plasma in cardiac surgery
      were included. Six small trials were found that included a total of 363
      participants with six different dose regimens of fresh frozen plasma. The overall
      quality of the studies was poor due to small patient numbers and lack of
      allocation concealment. There was no evidence that the prophylactic use of fresh
      frozen plasma affected peri-operative blood loss in cardiac surgery. There was
      some evidence that it may improve platelet count and fibrinogen concentration.

PMID- 15144293
TI  - A prospective, randomised, single-blind pilot study to determine the effect of
      anaesthetic technique on troponin T release after off-pump coronary artery
      surgery.
AB  - Ischaemic damage to the myocardium inevitably occurs during coronary artery
      surgery. However, the extent of the damage may be influenced by the anaesthetic
      technique used. The most sensitive and reliable marker of myocardial damage is
      currently thought to be troponin T. We conducted a prospective, randomised,
      single-blind pilot study to determine the baseline values of troponin T release
      after off-pump coronary artery bypass surgery in 30 patients randomly allocated
      to receive either propofol, isoflurane or isoflurane and high thoracic epidural
      analgesia. All other treatment was standardised. Patients undergoing emergency
      surgery and those with unstable angina were excluded. Blood samples were taken at
      0, 3, 6, 12, 24 and 48 h after surgery for troponin T analysis. Mean troponin T
      levels at 24 h were not significantly different between the groups (p = 0.41).
      These data allows appropriate power calculations for further, large-scale studies
      to determine the anaesthetic technique that provides optimal myocardial
      protection.

PMID- 15144296
TI  - The effects of intrathecal diamorphine on gastric emptying after elective
      Caesarean section.
AB  - This study investigated whether intrathecal diamorphine affects gastric emptying
      following elective Caesarean section. Forty women were randomly allocated to
      receive either diamorphine 300 microg or 0.9% saline as part of a standard spinal
      anaesthetic. Gastric emptying was measured in the immediate postoperative period
      using paracetamol absorption. Paracetamol concentrations were measured by
      enzymatic assay method using a Beckman CX-7 automated analyser. The time to
      maximum concentration (Tmax) was statistically longer in the diamorphine group
      (control 41.8, SD 20.8 min; diamorphine 72.6 SD 41.9 min; p < 0.01). During the 2
      h study period, mean morphine consumption via a patient controlled analgesia
      device was significantly higher in the control group (control 9.3, SD 3.6 mg;
      diamorphine 2.1, SD 2.1 mg; p < 0.01). We conclude that intrathecal diamorphine
      may contribute to the delay in gastric emptying that occurs immediately following
      elective spinal Caesarean section.

PMID- 15144295
TI  - A comparison of nefopam and clonidine for the prevention of postanaesthetic
      shivering: a comparative, double-blind and placebo-controlled dose-ranging study.
AB  - Postanaesthetic shivering is a frequent complication following general
      anaesthesia. The aim of this study was to compare the effectiveness of three
      doses of nefopam with clonidine and placebo in the prevention of postanaesthetic
      shivering. We studied 371 patients undergoing abdominal or orthopaedic surgery.
      Patients were allocated to one of five groups: Group A (n = 73) received 0.2 mg x
      kg(-1) nefopam, Group B (n = 75) 0.1 mg x kg(-1) nefopam, Group C (n = 76) 0.05
      mg x kg(-1) nefopam, Group D (n = 73) 1.5 microg x kg(-1) clonidine, and Group E
      (n = 74) saline 0.9% as placebo. We found a significant reduction in the
      incidence of shivering in Group A compared to Group C and clonidine as well as to
      the placebo group. All active treatments reduced the incidence and the severity
      of shivering compared to placebo. At 5 min postoperatively clonidine-treated
      patients showed a significant decrease in MAP and a significantly lower Aldrete
      score compared to all other groups. No haemodynamic or sedative adverse events
      were observed in the nefopam-treated patients. The results of our study indicate
      that nefopam (0.2 mg x kg(-1)) is superior to clonidine (1.5 microg x kg(-1)) in
      the prophylaxis of postanaesthetic shivering and not accompanied by sedative or
      haemodynamic side-effects.

PMID- 15144297
TI  - The management of patients with morbid obesity in the anaesthetic assessment
      clinic.
AB  - One hundred and two patients with body mass indices of 37 kg x m(-2) or greater
      were interviewed in an outpatient assessment clinic over an 18-month period. All
      had been listed for elective surgery under general anaesthesia. All patients were
      given an explanation of the problems of morbid obesity in relation to
      anaesthesia. Three options were then offered to the patients: 1) to proceed with
      general anaesthesia as planned; 2) to undergo the planned procedure under some
      form of regional anaesthesia, or 3) to postpone surgery and attempt to lose
      significant amounts of weight. At this initial consultation, 24 patients chose
      option 1, 21 patients chose option 2, and 52 patients chose option 3. Four
      patients decided not to have the planned surgery. One patient decided to have his
      surgery performed at another hospital under general anaesthesia. Of the 52
      patients who opted to lose weight, only eight succeeded in reducing their body
      mass index (BMI) by 3 or more during the period of the study. Of these eight,
      only four had reduced their BMI to below 35. In this study, an explanation of the
      problems of obesity in relation to anaesthesia, in advance of the date of
      surgery, had a significant effect on the type of anaesthesia chosen by most
      morbidly obese patients that were interviewed. Unfortunately, of those who
      decided to try and lose weight, only the occasional patient achieved significant
      weight loss. Although a laudable and advocated aim, optimization of patients with
      regard to their weight proved impractical in our study.

PMID- 15144298
TI  - Effect of chronic beta-blockade on peri-operative outcome in patients undergoing
      non-cardiac surgery: an analysis of observational and case control studies.
AB  - Little is known about the effect of chronic beta-adrenoceptor antagonist therapy
      during the peri-operative period in patients undergoing non-cardiac surgery. We
      conducted a literature review to identify studies examining the relationship
      between chronic therapy and adverse peri-operative outcome. Eighteen studies were
      identified in which it was possible to ascertain the incidence of adverse cardiac
      outcomes in those patients who were and were not receiving chronic beta-blocker
      therapy. None of the studies demonstrated a protective effect of chronic beta
      blockade. The results of these studies were then combined and a cumulative odds
      ratio calculated for the likelihood of myocardial infarction, cardiac death and
      major cardiac complications. Patients receiving chronic beta-blocker therapy were
      more likely to suffer a myocardial infarction (p < 0.05). These findings differ
      from the published effects of acute beta-blockade. Reasons for this discrepancy
      are considered.

PMID- 15144299
TI  - Production of compound A and carbon monoxide in circle systems: an in vitro
      comparison of two carbon dioxide absorbents.
AB  - Two new generation carbon dioxide absorbents, DragerSorb Free and Amsorb Plus,
      were studied in vitro for formation of compound A or carbon monoxide, during
      minimal gas flow (500 ml x min(-1)) with sevoflurane or desflurane. Compound A
      was assessed by gas chromatography/mass spectrometry and carbon monoxide with
      continuous infrared spectrometry. Fresh and dehydrated absorbents were studied.
      Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration >or= 1
      kPa) with fresh absorbents was longer with DragerSorb Free (1233 (55) min) than
      with Amsorb Plus (1025 (55) min; p < 0.01). For both absorbents, values of
      compound A were < 1 ppm and therefore below clinically significant levels, but
      were up to 0.25 ppm higher with DragerSorb Free than with Amsorb Plus. Using
      dehydrated absorbents, values of compound A were about 50% lower than with fresh
      absorbents and were identical for DragerSorb Free and Amsorb Plus. With
      dehydrated absorbents, no detectable carbon monoxide was found with desflurane.

PMID- 15144300
TI  - Measurement of cardiac output by transpulmonary arterial thermodilution using a
      long radial artery catheter. A comparison with intermittent pulmonary artery
      thermodilution.
AB  - Cardiac output can be measured accurately by transpulmonary arterial
      thermodilution using the PiCCO (Pulsion Medical Systems, Munich, Germany) system
      with a femoral artery catheter. We have investigated the accuracy of a new 50 cm
      4 French gauge radial artery catheter and the ability to use the system with a
      shorter radial catheter. We studied 18 patients who had undergone coronary artery
      surgery and made three simultaneous measurements of cardiac output by arterial
      thermodilution and with a pulmonary artery catheter. The radial catheter was
      withdrawn in 5 cm increments and the measurements were repeated. We found close
      agreement between arterial thermodilution and pulmonary artery thermodilution
      with a mean (SD) bias of 0.38 (0.77) l x min(-1). Arterial thermodilution became
      unreliable once the catheter had been withdrawn by more than 5 cm. We conclude
      that cardiac output measurement with arterial thermodilution with a radial
      catheter is interchangeable with that derived from a pulmonary artery catheter,
      and that a centrally sited arterial catheter is required for accurate
      determination of cardiac output by transpulmonary arterial thermodilution.

PMID- 15144301
TI  - Ventilation of a model lung using various cricothyrotomy devices.
AB  - In this study we developed a model lung to compare the effectiveness of
      ventilation using four different cricothyrotomy devices. The Ravussin 13G cannula
      (VBM Medical), the Quicktrach cannula 4 mm ID (VBM Medical), the Melker cannula 6
      mm ID (Cook) and a cuffed tracheal tube 6 mm ID were used in turn to ventilate
      the model lung through a cricothyrotomy over a range of upper airway resistances.
      The 6 mm cuffed tracheal tube provided consistently good ventilation independent
      of upper airway resistance. The 6 mm ID Melker device provided at least
      reasonable and at best very good ventilation, whatever the patency of the upper
      airway. The Ravussin cannula could ventilate well with the jet ventilator with
      low upper airway resistance but could not ventilate at all with complete upper
      airway obstruction. The Quicktrach performed poorly with low upper airway
      resistance but well with increased upper airway resistance. With its easier
      insertion, fewer complications compared to a surgical cricothyrotomy, and the
      ability to use it with a standard anaesthetic circuit, the authors feel that the
      6 mm Melker canula is the technique of choice for emergency trans-tracheal
      ventilation.

PMID- 15144302
TI  - Dead space and paediatric anaesthetic equipment: a physical lung model study.
AB  - Untested assumptions have been made with regard to functional dead space in
      facemasks, filters and breathing systems used in children for the administration
      of inhalation anaesthesia. Total functional dead space was measured in various
      combinations of this equipment applied to a spontaneous ventilation lung model
      with parameter settings appropriate for infants of 7-8 kg. We found that
      functional dead space was too large to allow for spontaneous ventilation of the
      lungs when a breathing filter was fitted. There was minimal relationship between
      size of the facemask and functional dead space; however, the provision of 22-mm
      female inlets to facemasks achieved proportionately less functional dead space
      than with 15-mm male inlets. Regardless of the apparatus used and the magnitude
      of the dead space, the leak induced when a poorly fitting facemask was used
      dramatically reduced the dead space of the breathing system - to near optimal
      conditions - by moving the alveolar gas elimination point to within the facemask
      itself.

PMID- 15144303
TI  - Awake craniotomy for glioblastoma in a 9-year-old child.
AB  - We report the pre-operative preparation and anaesthetic management for resection
      of an intracerebral tumour during awake craniotomy in a 9-year-old boy. We
      believe this is the youngest patient reported to have undergone this procedure.
      The challenges of sedation and psychological care throughout the procedure are
      discussed. We conclude that the procedure can be performed safely and that it
      seems unacceptable to uphold an age restriction. We believe that it is the
      individual level of development of the child that determines suitability for this
      type of surgery.

PMID- 15144304
TI  - The use of bispectral index during a cardiopulmonary arrest: a potential
      predictor of cerebral perfusion.
AB  - A 62-year-old male underwent off-pump coronary artery grafting surgery while
      cerebral function was monitored with bispectral index (BIS). The BIS monitoring
      was continued into the immediate postoperative period, during which time the
      patient experienced a cardiopulmonary arrest. The changes in the BIS values
      helped the resuscitating team in assessing the cerebral response to the
      cardiopulmonary resuscitation.

PMID- 15144305
TI  - The impact of regional anaesthesia on outcome: a patient's perspective.
AB  - Peripheral nerve catheters are being used increasingly to manage acute pain.
      Whilst acknowledged as effective, their broader implications for patient outcome
      are less clear. In this case report, we describe the way in which not only was
      the pain management of an ischaemic leg successful via a sciatic nerve catheter,
      but decision-making around this strategy affected outcome.

PMID- 15144306
TI  - Canary needs help; send for Willie Sutton.

PMID- 15144307
TI  - Measuring tracheal pressure during jet ventilation.

PMID- 15144309
TI  - The Cyclimorph cough.

PMID- 15144311
TI  - A faulty Bain circuit.

PMID- 15144312
TI  - Terlipressin for cerebral perfusion pressure support in a patient with septic
      shock.

PMID- 15144314
TI  - Prefilled ephedrine syringes.

PMID- 15144313
TI  - Use of the harmonic scalpel in a patient with a permanent pacemaker.

PMID- 15144315
TI  - Sneddon's syndrome and anaesthesia.

PMID- 15144316
TI  - Carbon dioxide pneumothorax treatment with positive end-expiratory pressure.

PMID- 15144319
TI  - Inadvertent epidural administration of metaraminol.

PMID- 15144317
TI  - A leaking one-way rotating valve.

PMID- 15144320
TI  - Reduction in pulmonary shunt using the Open Lung Concept.

PMID- 15144321
TI  - Auscultation of the chest after tracheal intubation.

PMID- 15144322
TI  - The sterility of fentanyl vials.

PMID- 15144323
TI  - A serious incident with the Blease Frontline Genius anaesthetic machine.

PMID- 15144325
TI  - Failure of percutaneous tracheostomy forceps.

PMID- 15144327
TI  - 'Gas off' or 'vaporiser off'.

PMID- 15144328
TI  - Leak of TIVA from Y-connector.

PMID- 15144330
TI  - External cephalic version: a safe procedure? A systematic review of version
      related risks.
AB  - BACKGROUND: The Term Breech Trial has considerably increased the number of
      cesareans. External cephalic version (ECV) might be an effective method of
      lowering the rate of cesareans; its efficacy has been well established. However,
      although in the absence of anesthesia the risks are thought to be low, most
      studies have used populations too small to allow definite conclusions on version
      related risks. METHODS: In an attempt to make an inventory of these risks, we
      have systematically analyzed 44 studies, covering a total of 7377 patients from
      1990 to 2002. The studies used were derived from a Medline and Embase search.
      RESULTS: The most frequently reported complications were transient abnormal
      cardiotocography (CTG) patterns (5.7%). Persisting pathological CTG readings
      (0.37%) and vaginal bleeding occur rarely (0.47%). The incidence of placental
      abruption was even lower, at 0.12%. Fetomaternal transfusion was absent in five
      out of seven studies, with a mean incidence of 3.7%. Emergency cesareans were
      performed in 0.43% of all versions. Perinatal mortality was 0.16%. CONCLUSIONS:
      External cephalic version seems to be a safe procedure.

PMID- 15144331
TI  - Cerebrospinal fluid leptin levels in preeclampsia: relation to maternal serum
      leptin levels.
AB  - BACKGROUND: To determine whether cerebrospinal fluid (CSF) and circulating levels
      of leptin differ between women with preeclampsia and women who had an
      uncomplicated pregnancy. METHODS: Maternal serum and CSF leptin concentrations
      obtained in the third trimester of the gestation were compared in 16 women with
      mild preeclampsia and 23 normotensive pregnant women who underwent cesarean
      section. Before administering local anesthetic for spinal anesthesia, 2 mL CSF
      and 4 mL venous blood sample were taken and were stored at -30 degrees C until
      serum and CSF leptin levels were measured by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Mean CSF leptin concentrations were not significantly different
      between the two groups (preeclampsia 9.7 +/- 4.2 ng/mL, normotensive 13.6 +/- 4.3
      ng/mL, p = 0.952). Similarly, mean serum leptin concentrations were similar
      between the two groups (mild preeclampsia 21.7 +/- 7.1 ng/mL, normotensive 18.3
      +/- 6.7 ng/mL, p = 0.698). CSF leptin levels are inversely related to the serum
      leptin concentrations in preeclamptic patients (r = -0.87, p = 0.000). An inverse
      relationship was also detected between CSF and serum leptin levels in
      normotensive pregnant subjects (r = -0.66, p = 0.000). CONCLUSIONS: CSF and serum
      leptin levels were similar in patients with preeclampsia and normotensive
      pregnant women. However, the CSF leptin was negatively correlated with the serum
      leptin concentrations in preeclamptic and normotensive control subjects,
      suggesting that leptin enters the brain by a saturable transport system. Further
      work is needed to confirm our findings.

PMID- 15144332
TI  - A population-based risk factor scoring will decrease unnecessary testing for the
      diagnosis of gestational diabetes mellitus.
AB  - BACKGROUND: To determine the effectiveness of a population-based risk factor
      scoring to decrease unnecessary testing for the diagnosis of gestational diabetes
      mellitus (GDM). METHODS: We formed a risk factor scoring over five, which
      questions maternal age, body mass index and first-degree relatives with a
      diagnosis of diabetes mellitus, a prior macrosomic fetus and adverse outcome
      during the previous pregnancies. All participants underwent a 50-g glucose
      challenge test (GCT) followed by a 100-g oral glucose tolerence test (OGTT). We
      opened the 50-g GCT envelope if the participant had a risk score > or = 1 and
      opened the 100-g OGTT envelope if the 50-g GCT value was > or = 7.2 mmol/l. After
      all patients delivered we also built other strategies and tested their detection
      rates. RESULTS: Fourteen patients (3.3%) were diagnosed as having gestational
      diabetes mellitus via a 100-g OGTT. None of the patients with a score of zero had
      gestational diabetes mellitus. Logistic regression analysis revealed that an
      increase in the score by one caused a three times increase in gestational
      diabetes mellitus risk (OR = 3, CI = 1.9-5). Compared with the universal
      screening, our strategy to screen if the risk score was > or = 1, followed by a
      50-g GCT with a 7.2-mmol/l cut-off value, decreased the number of women to be
      screened by 30% and diagnosed all cases with GDM. Screening the patients with a
      score > or = 2 would have decreased the number of women to be screened by 63%,
      still diagnosing 85% of cases with GDM. Also, risk factor-based screening
      strategies cause a 50% and 53% reduction in the number of OGTT applied,
      respectively. CONCLUSION: A well integrated, population-based scoring will
      decrease the number of unnecessary testing but still diagnose 85-100% of GDM
      cases.

PMID- 15144333
TI  - Etiology and outcome of fetuses with functional heart disease.
AB  - BACKGROUND: The aim of this study was to assess the etiology and outcome of
      fetuses with functional heart disease as detected by echocardiography. METHODS:
      In total, 51 fetuses (median gestation age of 28.6 weeks) were included. The
      inclusion criteria were hydrops (n = 14), pericardial effusion (PE; n = 9),
      tricuspid valve regurgitation (TR; n = 8), hypertrophic cardiomyopathy (HCM; n =
      7) and dilated cardiomyopathy (DCM; n = 7). Antenatal management was performed
      for 17 of 51 fetuses (33%): two abortions, nine digoxin administrations, three
      thoracocenteses, one pericardial puncture, one blood transfusion and one ascites
      centesis. RESULTS: The etiology of functional heart disease was twin pregnancy in
      18, fetal lung lesions in five, maternal diabetes in five, fetal anemia in four,
      extracardiac or chromosomal abnormalities in three, infection in three, teratoma
      or arteriovenous malformation in four, indomethacin administration in two,
      endocardial fibroelastosis in two, maternal anaphylaxia in one, idiopathic
      arterial calcification of infancy (IACI) in one, pregnancy-induced hypertension
      (PIH) in one, and unknown in two fetuses. There was no significant difference
      between fetuses with and without treatment (53% vs. 79%; p = 0.06). There were
      two stillbirths and 12 postnatal deaths (29%). Among 35 surviving infants, 85%
      were free of symptoms in the follow-up (mean 3.9 years). CONCLUSIONS: These
      findings indicate that a functional heart disease in utero is associated with
      very varying etiology and high mortality. Improved understanding of the
      hemodynamic findings may lead to treatment that is more successful.

PMID- 15144334
TI  - High-density lipoprotein and homocysteine levels correlate inversely in
      preeclamptic women in northern Nigeria.
AB  - BACKGROUND: Preeclampsia/eclampsia is one of the most common complications of
      pregnancy. It is a cause of high morbidity for both mother and fetus, especially
      in developing countries. In a recent survey conducted in Gombe, Nigeria,
      eclampsia was found to be a major cause of maternal mortality (24.2%), second
      only to obstetric hemorrhage (27.1%). Previous studies have produced
      contradictory findings regarding total homocysteine (tHcy) levels in women with
      preeclampsia/eclampsia and there is little information about the relationship
      between particular serum lipids and tHcy. The objective of this study in Gombe
      was to compare the levels of serum lipids and homocysteine in healthy pregnant
      women and women with preeclampsia/eclampsia in Nigeria. METHODS: The experimental
      subjects included 43 women with preeclampsia/eclampsia and 130 healthy pregnant
      women served as controls. The criteria for preeclampsia/eclampsia included the
      following: hypertension (blood pressure > 140/90 mmHg), total protein (> 190 mg/g
      creatinine), and edema. Blood sera obtained from patients and controls attending
      the prenatal clinics at the Specialist Hospital and the Federal Medical Center in
      Gombe were analyzed for tHcy, total cholesterol, triglycerides, high-density
      lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol,
      antioxidant capacity, folate, and vitamin B-12. RESULTS: The mean tHcy
      concentration for the preeclamptic/eclamptic women was greater than that of the
      controls (10.1 vs. 8.4 micromol/l, respectively, p = 0.01). The mean
      concentrations of LDL-cholesterol and triacylglycerols were not different between
      the two groups. However, the mean HDL-cholesterol level was higher in the healthy
      pregnant women compared with the preeclamptic/eclamptic women (1.64 vs. 1.42
      mmol/l, respectively, p = 0.02). The HDL-cholesterol concentration was correlated
      inversely with the tHcy concentration (p = 0.001, r = 0.51). Total homocysteine
      was not linked with either serum folate or vitamin B-12. CONCLUSIONS: These
      results show that preeclampsia/eclampsia is associated with increased tHcy levels
      and that HDL levels are depressed in Nigerian women with this hypertensive,
      pregnancy associated disorder.

PMID- 15144336
TI  - Multiple birth and cerebral palsy in Europe: a multicenter study.
AB  - BACKGROUND: A European multicenter study (Surveillance of Cerebral Palsy in
      Europe, SCPE) was used to describe changes over time in multiple birth rates and
      cerebral palsy (CP) rates among multiple born infants, to compare CP rates and
      clinical types between multiples and singletons, and to analyse the influence of
      birth order in twins. METHODS: Data were collected from 12 European population
      based CP registers on 6613 children born in 1975-90, as well as demographic data.
      RESULTS: The rate of multiple birth in the populations increased from 1.9% in
      1980 to 2.4% in 1990, and the proportion of multiples among CP infants increased
      from 4.6% in 1976 to 10% in 1990. Multiples have a four times higher rate of CP
      than singletons [7.6 vs. 1.8 per 1000 live births, relative risk (RR) 4.36; 95%
      confidence interval (CI) 3.76-4.97] overall. The risk is marginally higher in
      multiples with birthweight > 2500 g (RR 1.60; 95% CI 0.95-2.28) and born at term
      (RR 1.65; 95% CI 0.91-2.40), and there is no difference in the risk for the low
      birthweight and preterm groups. Correcting for differences in gestational age and
      birthweight, the clinical type of CP was the same in multiples and singletons.
      Twin CP infants are more often second than first born (56% vs. 44%, p < 0.05).
      CONCLUSIONS: Multiple born infants have a four times higher risk of developing
      cerebral palsy than singletons, mainly related to the higher risk of preterm
      birth in multiples. As the rate of multiples doubled through the 1980s, cerebral
      palsy cases in multiples increased in the same period.

PMID- 15144335
TI  - Elevated plasma homocysteine levels in gestational diabetes mellitus.
AB  - OBJECTIVE: This prospective study investigated the occurrence of
      hyperhomocysteinemia in a population of patients with gestational diabetes. The
      aim was to determine whether elevated plasma homocysteine is associated with
      gestational diabetes in Turkish women. STUDY DESIGN: This prospective controlled
      study was conducted in the Department of Obstetrics and Gynecology of the Baskent
      University Faculty of Medicine between April 2002 and June 2003, and involved 304
      Turkish women with uncomplicated pregnancies who were at 24-28 weeks gestation.
      The women in the study were assigned to one of three groups according to the
      results of the 50-g glucose screening and the oral glucose tolerance test (OGTT):
      group 1 comprised women who had normal glucose levels (< or = 135 mg/dL) after
      the 50-g challenge; group 2 comprised women with abnormal screening test results
      (> 135 mg/dL) but normal OGTT results; and group 3 comprised patients with
      gestational diabetes mellitus (GDM) according to the OGTT. Levels of fasting
      glucose, homocysteine, vitamin B(12) and folic acid, total cholesterol, high
      density lipoprotein (HDL) cholesterol, and triglycerides, low density lipoprotein
      (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol levels were
      measured in the three groups. Levels of insulin sensitivity were calculated using
      the homeostasis model assessment (HOMA) formula. RESULTS: The mean level of
      homocysteine in group 1 was significantly lower than the levels in groups 2 and 3
      (p < 0.001) The mean triglyceride and VLDL levels in group 3 were significantly
      higher than the corresponding levels in group 1 (p < 0.05 for both). There were
      no significant differences among the groups with respect to levels of total
      cholesterol, vitamin B(12), folic acid, creatinine, fasting glucose or insulin.
      The mean HOMA value in group 3 was significantly higher than that in group 1 (p <
      0.05). Only the blood glucose level after the 50-g glucose screening [p = 0.000,
      95% confidence interval (CI) 0.009-0.027] had a significant correlation with
      homocysteine levels. CONCLUSION: In this prospective study of Turkish women, we
      found that patients with gestational diabetes and women with abnormal screening
      test results (> 135 mg/dL) but normal OGTT results have higher homocysteine
      levels than normal pregnant women. This increased level seems to be related to an
      abnormal 50-g test but not to insulin resistance. Further investigations are
      needed to follow up for these patients in the postpartum period and later in
      their life.

PMID- 15144337
TI  - Maternal and neonatal outcome of 93 consecutive triplet pregnancies with 71%
      vaginal delivery.
AB  - BACKGROUND: The aim of this study was to investigate neonatal and maternal data
      in a large series of triplet pregnancies as a function of the decision regarding
      the route of delivery. METHODS: A retrospective series of 93 triplet pregnancies
      managed and delivered between 1989 and 2001 in a single perinatal department was
      analyzed. Seventy-eight women with triplet gestations who underwent a trial of
      labor were compared with 15 women with triplet gestations who delivered their
      infants by elective cesarean delivery. Neonatal outcomes assessed included
      respiratory distress syndrome, retinopathy of prematurity, necrotizing
      enterocolitis, intraventricular hemorrhage and Apgar scores. Maternal outcomes
      assessed included preeclampsia, blood transfusion, endometritis and urinary tract
      infection. RESULTS: Sixty-six of 78 women (84%) who underwent a trial of labor
      had a successful vaginal delivery of all three neonates. The other 12 delivered
      their infants by cesarean delivery. Perinatal mortality referred to 104 triplet
      pregnancies was 48/1000. CONCLUSIONS: Our experience suggests that offering
      vaginal delivery is an acceptable management plan for triplet gestation in a
      center with a sufficient number of triplet deliveries.

PMID- 15144338
TI  - Vaginal hematoma during parturition: a population-based study.
AB  - BACKGROUND: Vaginal hematoma is a rare but painful complication during and after
      childbirth, with little information in the literature regarding risk factors and
      management. Aim. To study the risk factors in a national population-based
      registry. SETTING: All births in Sweden from 1987 to 2000 inclusive. METHODS:
      Data were analyzed using the Mantel-Haenszel technique, with odds ratio (OR) and
      95% confidence interval (CI), adjusting for maternal age, parity and birthweight.
      RESULTS: Nulliparity was a strong risk factor (OR 3.63, 95% CI 3.25-4.08), as was
      maternal age over 29 years and a birthweight exceeding 4000 g. Irrespective of
      year of delivery the mother stayed an extra 1.3-1.7 days in hospital following
      this complication. CONCLUSION: Risk factors for vaginal hematoma during delivery
      include primiparity and a maternal age > 29 years.

PMID- 15144339
TI  - Nordic gynecologists' opinion on quality assessment registers.
AB  - BACKGROUND: The Board of the Nordic Federation of Societies of Obstetrics and
      Gynecology established a Quality Group for Gynecological Surgery connected with
      benign diseases with one member from each of the Nordic countries. The aim was to
      suggest guidelines for the quality assessment of such surgery. METHODS: A
      questionnaire study was carried out in all Nordic gynecological departments
      concerning quality assessment and the elaboration of guidelines. RESULTS: Most of
      the departments (80.4%) want to participate in establishing and maintaining a
      quality register. The majority of responders strongly agree that registers detect
      areas of satisfactory as well as unsatisfactory quality, and are necessary for
      comparison of treatment results among departments. Several departments are
      hesitant about joining a register if it will incur financial costs (59.5%) and/or
      extra work (47.6%). Most departments (71.4-94.6%) consider that all major
      gynecological surgery should be monitored. The departments agree that pre-, per-,
      and post hospital patient events should be included in any register. These
      results are incorporated into common general guidelines for quality assessment of
      gynecological surgery in the Nordic countries. CONCLUSION: The gynecological
      departments in the Nordic countries agree on the necessity for and the main
      content of registers for quality assessment, but the interest drops when extra
      work is needed, and if the departments have to pay to participate, which
      emphasize the need for simple and low-cost registers. In accordance with the
      results of the Nordic questionnaire, common general quality guidelines for
      gynecological surgery are suggested.

PMID- 15144340
TI  - A longitudinal study on different models of postabortion care in Tanzania.
AB  - OBJECTIVE: To identify women having unsafe abortions and elucidate whether an
      acceptable follow-up rate among these women can be retrieved. STUDY POPULATION:
      One thousand three hundred and fifty-seven women attended Temeke Municipal
      Hospital, Dar es Salaam with an abortion-related diagnosis. METHODS: Women having
      unsafe abortions were identified by an empathetic dialogue, offered a
      contraceptive service and asked to return for follow-up. Three different ways of
      achieving follow-up information were tested. In phase 1, a combination of
      hospital-based and home-based interviews was utilized, in phase 2, an additional
      1-month control visit was added to the protocol, and in phase 3, the
      contraceptive counseling and service was provided by technically well-skilled
      counselors. RESULTS: Seven hundred and eighty-eight women were identified as
      having had unsafe abortions and 491 women as spontaneous abortions. Women having
      unsafe abortions were younger, more often single and of higher parity than women
      having spontaneous abortions. The follow-up rate achieved varied from 47%-72%,
      being lowest in phase 1 and highest in phase 3. The two most common reasons for
      loss to follow-up were the interviewer's inability to locate the respondent's
      house either because of an unspecific or a remote address (58%) and migration
      (29%). CONCLUSION: If hospital-based and confidential home-based interviews are
      used combined and if the women having unsafe abortions are counseled by
      technically well-skilled counselors, it is possible to achieve a reasonable
      follow-up rate among women having unsafe abortions.

PMID- 15144341
TI  - Pulmonary embolism associated with combined oral contraceptives: reporting
      incidences and potential risk factors for a fatal outcome.
AB  - BACKGROUND: It is established that combined oral contraceptive (COC) treatment
      increases the risk of a pulmonary embolism (PE), but specific risk factors for a
      fatal outcome from a PE remain to be determined. This study aimed to identify
      such risk factors, and to calculate the reporting rates of fatal and non-fatal
      PE. METHODS: Cases of suspected PE during treatment with COCs reported to the
      Swedish Adverse Drug Reactions Advisory Committee (SADRAC) between 1965 and 2001
      were included. Medical records were scrutinized for potential risk factors for a
      venous thromboembolism (VTE). Annual sales data were obtained from the National
      Corporation of Pharmacies. RESULTS: A total of 248 cases of a suspected PE were
      reported; 207 non-fatal and 41 fatal. A VTE was verified in all fatal, and in
      83.5% of non-fatal cases. The presence of nausea or abdominal pain, an age >35
      years, concomitant treatment with other drugs which may increase the VTE risk,
      vein or lymph vessel malformation, and a deep vein thrombosis above the knee
      level were positively associated with a fatal outcome. Chest pain and previous
      COC use were negatively associated with a fatal outcome. The reporting rate of a
      PE with a verified VTE was 1.72 (95% confidence interval 1.47-2.00) cases per 100
      000 treatment years, and of a fatal PE 0.25 (95% confidence interval 0.16-0.37)
      cases per 100 000 treatment years. CONCLUSION: Several specific potential risk
      factors for a fatal outcome from a COC-induced PE were identified. Recognition of
      these in combination with a high suspicion of VTE in COC users may reduce the
      risk of a fatal outcome.

PMID- 15144342
TI  - Fatty acid synthase expression and clinicopathological findings in endometrial
      cancer.
AB  - BACKGROUND: Over-expression of fatty acid synthase (FAS), the enzyme involved in
      the anabolic conversion of dietary carbohydrates to fatty acid, has been reported
      in many human malignancies. This study investigated whether clinicopathological
      findings [histological grade, myometrial invasion, vessel permeation, lymphatic
      permeation, nodal metastasis, and Federation of International Gynecologic
      Obstetrics (FIGO) stage] and body fat distribution differ with the level of FAS
      expression in endometrial cancer. METHODS: Subjects were 73 postmenopausal women
      (mean age, 62.2 +/- 7.4 years; range, 49-75 years) with endometrioid
      adenocarcinoma. Baseline characteristics included age, height, body weight (BW),
      body mass index (BMI), and years since menopause (YSM). Percentage of body fat
      and the trunk-leg fat mass ratio were measured by dual-energy X-ray
      absorptiometry. FAS expression was determined using immunohistochemical methods
      in formalin-fixed and paraffin-embedded cancer specimens. FAS expression was
      defined as none, low, and high. RESULTS: Sixty-six (90.4%) cases showed positive
      FAS status. Sixty-nine percent of cases showed myometrial invasion > or =1/2, 50%
      of cases showed myometrial invasion <1/2, and 23% of cases without myometrial
      invasion demonstrated a positive FAS status. Lymphatic permeation, vessel
      permeation, nodal metastasis, and advancing FigO stage were associated with FAS
      status. The trunk-leg fat ratio and BMI in high and low FAS status groups were
      significantly greater than that in those not expressing FAS (p < 0.05). However,
      age, height, weight, YSM, and percentage of body fat did not differ with FAS
      status. CONCLUSION: FAS expression in endometrial cancer is associated with
      cancer progression and upper body fat distribution.

PMID- 15144343
TI  - Power Doppler vascularity index for predicting the response of neoadjuvant
      chemotherapy in cervical carcinoma.
AB  - BACKGROUND: To evaluate whether the power Doppler vascularity index (PDVI) can
      predict the response to neoadjuvant chemotherapy (NACT) in cervical carcinoma.
      METHODS: Twenty-five women with bulky early stage cervical carcinoma treated by
      NACT followed by surgery were enrolled. Their response to NACT was evaluated.
      Clinical characteristics and pathologic data were recorded. Transvaginal power
      Doppler was performed before, during and after NACT. PDVI was detected using
      power Doppler and a quantitative image processing system. Factors that can
      potentially correlate with the response to NACT were analyzed. RESULTS: Twelve
      (48%) patients showed a response (responders) to NACT and 13 (52%) were unchanged
      or had progressive disease (nonresponders) after NACT. Higher PDVI values were
      noted in tumors with lymphovascular emboli and pelvic lymph node metastasis both
      before and after NACT. The mean values of the PDVI of the nonresponders before
      (19.27 +/- 6.01 vs. 12.28 +/- 7.06, p = 0.014), during (20.2 +/- 1.5 vs. 12.9 +/-
      2.1, p = 0.009) and after NACT (18.1 +/- 6.0 vs. 9.3 +/- 5.4, p = 0.001) were
      significantly higher than those of the responders. When the cutoff point for
      predicting nonresponders to NACT was set at a PDVI value of 15%, the sensitivity
      was 92.3% and the specificity 66.7%. CONCLUSIONS: The power Doppler vascularity
      index can predict the response to neoadjuvant chemotherapy in cervical cancer,
      and might be useful for the evaluation of response to chemotherapy in cancer
      patients in the future.

PMID- 15144345
TI  - Heavy uterine bleeding due to uterine arteriovenous malformations.

PMID- 15144344
TI  - Very large Skene's duct cyst.

PMID- 15144346
TI  - Successful management of obstructed labor in a patient with multiple hydatid
      cysts.

PMID- 15144347
TI  - Twin pregnancy with a complete hydatidiform mole and co-existing fetus.

PMID- 15144348
TI  - Plasmodium falciparum infection as an unexpected cause of anemia in a healthy
      parturient.

PMID- 15144349
TI  - Tibolone.

PMID- 15144351
TI  - Physical activity in young children--does it matter?

PMID- 15144352
TI  - Exercise therapy for people with rheumatoid arthritis and osteoarthritis.
AB  - Exercise therapy would appear to be effective at increasing aerobic capacity and
      muscle strength in patients with rheumatoid arthritis (RA), and no detrimental
      effects on disease activity or pain compared with controls has been observed.
      Exercise therapy--at least in the short-term, improves pain, muscular strength
      and function in elderly people with mild osteoarthritis (OA) of the hip or knee.
      For the treatment of both OA and RA the knowledge of the optimal type, frequency,
      duration and intensity of exercise is still limited, but the exercise should not
      include high-impact loads or high injury risk. Long-term compliance is important
      in achieving long-term benefits. Supervised classes appears to be as effective as
      treatments provided on a one-to-one basis, group-based exercise programme thus
      providing a cost-effective alternative. Adherence to home programmes seems to be
      lower. Future research should focus on finding optimal type and dose of exercise,
      ways of optimally maintaining the beneficial effects of exercise therapy over
      time as well as on the effects of exercise on the long-term progression of the
      disease and cost-effectiveness of the therapy.

PMID- 15144353
TI  - Physical activity as a preventive measure for coronary heart disease risk factors
      in early childhood.
AB  - Physical activity causes acute physiological and long-term adaptive responses in
      the body. It is a protective factor for coronary heart disease (CHD) in adults.
      It has been assumed that children younger than 8 years of age may be in general
      active enough and there would be hardly any relationships between physical
      activity and CHD risk factors in early childhood. One hundred and fifty-five
      children (age 4-7 years) participated in this physical activity study during
      three consecutive years. Physical activity was examined twice a year with a
      special-purpose physical activity diary. CHD risk factors were measured during
      annual health care visits in the Specific Turku Coronary Risk-Factor Intervention
      Project (STRIP). We found that physical activity was related to CHD risk factors
      in early childhood. Among the girls, low-activity playing was related to a higher
      BMI. At the mean age of 6 years, high-activity playing was negatively related to
      serum total cholesterol (r=-0.32*) and positively to the high-density lipoprotein
      (HDL)/total cholesterol ratio (r=0.37**). The negative relationship between high
      activity playing and triglycerides was highest (r=-0.32*) at the mean age of six.
      Among 4-year-old boys, playing outdoors correlated positively with serum HDL
      cholesterol concentration (r=0.29*) and the HDL/total ratio (r=0.35**). At the
      age of 5 years, physically active playing correlated positively with systolic
      blood pressure (r=0.25*). Playing outdoors and high-activity playing already have
      important health-maintaining effects in 4-7-year-old children. These positive
      effects differ between genders. (*P<0.05 **P<0.01)

PMID- 15144354
TI  - Secular trends in physical fitness and obesity in Danish 9-year-old girls and
      boys: Odense School Child Study and Danish substudy of the European Youth Heart
      Study.
AB  - INTRODUCTION: Low physical fitness and obesity have been shown to be associated
      with cardiovascular disease (CVD) risk. Obesity is on the increase in many
      countries, but little is known about physical fitness trends. Monitoring of
      changes in fitness and obesity in the population is important for preventive
      strategies, and the aim of this study was to analyse the secular trends in
      fitness and body composition in Danish children. MATERIALS AND METHODS: Two
      representative population studies were conducted 12 years apart on 9-year-old
      children in the same location: the Odense School Child Study in 1985-86 and the
      European Youth Heart Study in 1997-98. In both studies, physical fitness was
      determined by a maximal cycle ergometer test, and obesity was assessed by
      skinfolds. RESULTS: Boys had a lower physical fitness and were fatter in 1997-98
      than in 1985-86. In addition, an increased polarization is emerging, with the
      difference between the fit and the unfit and the difference between the lean and
      the fat being greater in 1997-98 than in 1985-86. In girls, a similar
      polarization was found, but no overall change in fitness or obesity. CONCLUSION:
      The negative trend and increased polarization for physical fitness and obesity in
      Danish children suggest a future generation with a higher degree of CVD risk.

PMID- 15144355
TI  - Muscle temperature and sprint performance during soccer matches--beneficial
      effect of re-warm-up at half-time.
AB  - The relationship between quadriceps muscle temperature (T(m)) and sprint
      performance was evaluated during soccer matches in 25 competitive players. In one
      game, T(m) was determined frequently (n=9). In another game, eight players
      performed low-intensity activities at half-time (re-warm-up, (RW), whereas
      another eight players recovered passively (CON). T(m) was 36.0+/-0.2 degrees C at
      rest and increased (P<0.05) to 39.4+/-0.2 degrees C before the game and remained
      unaltered during the first half. At half-time, T(m) decreased (P<0.05) to 37.4+/
      0.2 degrees C, but increased (P<0.05) to 39.2+/- degrees C during the second
      half. In CON and RW, T(m) and core temperature (T(c)) were similar before and
      after the first half, but 2.1+/-0.1 and 0.9+/-0.1 degrees C higher (P<0.05),
      respectively, in RW prior to the second half. At the onset of the second half,
      the sprint performance was reduced (P<0.05) by 2.4% in CON, but unchanged in RW.
      The decrease in T(m) was correlated to the decrease in performance (r=0.60,
      P<0.05, n=16). This study demonstrates that in soccer, the decline in T(m) and
      T(c) during half-time is associated with a lowered sprint capacity at the onset
      of the second half, whereas sprint performance is maintained when low-intensity
      activities preserve muscle temperature.

PMID- 15144356
TI  - Identification of prognostic indicators for patient outcomes in extensor
      tendinopathy at the elbow.
AB  - Extensor tendinopathy is a degenerative overuse condition involving the common
      extensor tendon at the lateral humeral epicondyle. The diagnosis and management
      of this condition are clinically based. Our aims were to determine if through
      patient history and clinical examination we could ascertain prognostic factors
      affecting time to symptom resolution in extensor tendinopathy. Symptomatic
      patients (N=28) had a thorough history and examination, and rehabilitation
      monitored regularly for 6 months. Patient outcomes at 6 months were then
      correlated with specific factors on initial presentation. Factors implicated as
      having prognostic significance regarding patient outcomes were a current history
      of manual work (P=0.04, effect size -0.29), and a current history of weekly
      participation in racquet sports (P=0.01, effect size -0.41). These individual
      factors had a significantly decreased chance of symptom resolution at the 6-month
      stage, and when combined had an effect size of -0.6 (P=0.001). Negative patient
      outcomes may be related to current high and repetitive levels of tendon stress,
      and rest from recreational and occupational use of wrist extensor tendons may be
      necessary to enhance the chances of complete symptom resolution. Enforced rest
      has monetary and quality-of-life implications, but is probably preferable to an
      incomplete recovery and prolonged tendon pain and dysfunction.

PMID- 15144357
TI  - Low-back pain in adolescents is associated with poor hip mobility and high body
      mass index.
AB  - The objective of this cross-sectional study was to investigate whether body mass
      index (BMI) and hip mobility are associated with low-back pain (LBP) in
      adolescents. The study population included all adolescents in 8th and 9th grades
      in a rural and in an urban area in Eastern Norway. Eighty-eight adolescents
      participated (mean age 14.7 years), making the response rate 84%. LBP was
      assessed by a questionnaire answered in the classrooms as pain/discomfort in the
      low back during the preceding year. Body height and weight were measured, and BMI
      was calculated. Hip mobility was measured as active movements by a goniometer.
      The level of significance was set to P< or =0.05. In bivariate analysis for the
      whole group, LBP was associated positively with a higher than mean BMI, while LBP
      among boys was associated with a less than mean hip flexion, internal rotation,
      and hamstrings flexibility. In multiple regression analyses, adjusting for gender
      and well-being, LBP was associated with a higher than mean BMI, a less than mean
      hamstrings flexibility, and a less than mean hip flexion. The results suggest
      further prospective research to investigate whether poor hip mobility and high
      BMI may predict juvenile LBP.

PMID- 15144358
TI  - Skeletal muscle and hormonal adaptations to circuit weight training in untrained
      men.
AB  - Twelve men either performed 10 weeks of timed circuit weight training 3 days
      week(-1) (CWT; n=8; X+/-SE; age=23.6+/-1.8 years), or were part of a sedentary
      control group (n=4; age=20.5+/-1.0 years). Significance was P<0.05 for all
      analyses. The CWT program significantly increased 1 repetition maximum (1 RM)
      strength for nine of 10 exercises (15-42%). Although no body composition measure
      significantly changed for the CWT group, low-to-moderate effect sizes were
      evident for body weight, lean body mass, and relative fat. CWT did not alter
      percent fiber type, but did increase cross-sectional areas for type IIA fibers
      (microm(2); pre=5988+/-323, post=7259+/-669). Relative (%) myosin heavy-chain
      (MHC) expression increased for MHC IIa (pre=42.5+/-2.7, post=50.1+/-2.6), and
      decreased for MHC IIb (pre=21.8+/-2.8, post=15.4+/-2.4) for the CWT group. Serum
      testosterone, cortisol, and the testosterone/cortisol ratio did not change at any
      time for the CWT group. None of the measured variables changed for the control
      group. These data indicate that for untrained subjects, CWT of the type used
      resulted in improved muscular strength and a tendency toward increased lean mass.
      Compared with other types of weight training, fewer adaptations of the muscle
      fibers were evident. This is likely due in part to the relatively low loads used
      with this type of resistance exercise.

PMID- 15144359
TI  - Different frequency treadmill running in immobilization-induced muscle atrophy
      and ankle joint contracture of rats.
AB  - We investigated the effects of different frequencies of treadmill running on
      immobilization-induced soleus and gastrocnemius muscle atrophy and ankle joint
      contracture in rats using morphology and histochemistry. The right ankle joint of
      rat was immobilized for 2 weeks. Thereafter, the rats were randomly assigned to
      four groups for 6 weeks of exercise under different conditions: free cage
      activity and free remobilization (FR), once-a-week treadmill running (low
      frequency running program (LFR)), three-time-a-week running (middle-frequency
      running program (MFR)), and six-time-a-week running (high-frequency running
      program (HFR)) groups. Two weeks of immobilization significantly reduced the
      cross-sectional area of soleus type I (62%, P<0.05) and type II muscle fibers
      (66%, P<0.05), gastrocnemius type I (78%, P<0.05) and type II muscle fibers (68%,
      P<0.05), and the range of ankle joint movement (46%, P<0.05). Immobilization also
      increased the ratio of type II to total fiber numbers in the soleus (P<0.05), and
      gastrocnemius (P<0.05), and induced pathological changes in muscle fibers. Some
      of these changes could not be corrected by free remobilization; however, the LFR,
      MFR, and HFR groups clearly recovered toward normal levels with exercise
      frequency, the effect on muscle recovery being more beneficial in the MFR and HFR
      groups. In addition, the range of ankle joint contracture was improved in LFR,
      MFR, and HFR groups in comparison with that in the FR group. These findings
      indicate that treadmill running exercise improved the immobilization-induced
      muscle fiber histochemical alterations and the range of the ankle motion in rats.
      Running three times and six times a week was more beneficial for recovery of
      immobilization-induced muscle atrophy and joint contracture compared with no
      running or once-a-week running.

PMID- 15144360
TI  - Effect of motivational climate on sportspersonship among competitive youth male
      and female football players.
AB  - The purpose of this study was to investigate the influence of perceived
      motivational climate and gender on sportspersonship behavior of competitive youth
      football players. Participants were 512 boy and 202 girl Norwegian youth football
      players (12-14 years old) competing in an international football tournament. A 2
      x 2 x 2 (gender, mastery climate high and low, performance climate high and low)
      MANOVA produced no multivariate or interaction effects, but main effects for
      gender, performance climate, and mastery climate did emerge. Post hoc analyses of
      the simple main effects found that boys and girls were different in
      sportspersonship, but only in that boys were more sportspersonlike than girls on
      one of the four sportspersonship dimensions. Players perceiving a high mastery
      climate endorsed sportspersonship more than those players perceiving a low
      mastery climate, and players perceiving a high performance climate were less
      likely to endorse sportspersonship than players perceiving a low performance
      climate. Canonical correlation analysis revealed that a strong mastery climate
      was positively associated with commitment, respect for social conventions, and
      respect for rules and officials. A strong performance climate was negatively
      associated with respect and concern for social conventions and respect for rules
      and officials, while a positive association emerged for respect and concern for
      the opponent. The results of our study suggest that both boys and girls may well
      perceive the coach emphasizing similar criteria of success and failure and
      thereby a similar culture of sportspersonship, while in general a strong mastery
      climate leads to a higher sportspersonship orientation.

PMID- 15144363
TI  - The nurse stump.

PMID- 15144364
TI  - Healthy behaviors and sources of health information among low-income pregnant
      women.
AB  - This article addresses responses from two open-ended questions, describing the
      healthy behaviors and sources of health information in 150 low-income pregnant
      women. Data for this exploratory study were collected as part of a larger
      descriptive correlational study. Qualitative content analysis was used in the
      analysis. One hundred fifty English-speaking pregnant women aged 18 and over were
      interviewed at a public prenatal clinic in the Southeastern United States at
      their first prenatal visit. Health behaviors were placed into seven mutually
      exclusive categories: food-related behaviors, substance-related behavior,
      exercise/rest/activity, self-awareness/appearance, learning, focus on baby, and
      no specific behaviors. Sources of information questions were placed into seven
      mutually exclusive categories: family, health personnel, reading, hearing, other
      people, self-intuitive, and no response. Low-income pregnant women are aware of
      healthy behaviors and report practicing them during their pregnancies. Because
      family members are a common source of information for health practices, they
      should be included in health education efforts.

PMID- 15144366
TI  - Barriers to effective contraception and strategies for overcoming them among
      adolescent mothers.
AB  - Young women often have difficulty accessing and correctly using contraception.
      However, these difficulties are not primarily the result of lack of knowledge or
      experience of contraception. In this study, nine adolescent mothers were
      interviewed about their experience of contraception before and after the birth of
      their children. These adolescent women faced barriers to effective contraceptive
      use before the birth of their children. These barriers included indifference to
      the possibility of pregnancy, perceived invulnerability to pregnancy, and
      forgetting to use contraception regularly. Analysis also revealed that during the
      time these women were sexually active prior to pregnancy, many had used a range
      of strategies to overcome these barriers to effective contraception, including
      using adult support, allowing an adult to take responsibility for contraception,
      and using multiple methods of contraception to cover for contraceptive failure.
      The strategies used by these women to delay childbearing indicate valuable areas
      for further research in preventing unplanned adolescent pregnancy.

PMID- 15144365
TI  - Nurse home visits to maternal-child clients: a review of intervention research.
AB  - Home visiting has been considered a promising strategy for addressing the
      multiple needs of families at risk. Research reviews are a valuable resource for
      researchers, policymakers, and practitioners who develop and support new home
      visiting interventions. This review examines 13 research studies published
      between the years of 1980 and 2000 that test the effectiveness of home-visiting
      interventions using professional nurses as home visitors. Findings indicate that
      a wide range of client problems are addressed during home visits using a variety
      of nursing interventions. Missing from most of the reports is a clear theoretical
      link between the client problem addressed, the nursing intervention, and target
      outcomes. About half of the studies were successful in achieving desired
      outcomes. Future research should be directed by middle-range practice theory,
      clearly explicate the nursing intervention being tested, use power analysis to
      determine sample size, and report reliability and validity of dependent variable
      measures with culturally diverse samples.

PMID- 15144367
TI  - Childhood vaccine risk/benefit communication among public health clinics: a time
      motion study.
AB  - United States law requires that immunization providers use Centers for Disease
      Control Vaccine Information Statements (VISs) and inform parents about vaccine
      risks and benefits prior to every childhood immunization. A recent national
      survey found that public health clinics (PHCs) reported high compliance with this
      law. To further investigate these findings, we conducted an immunization time
      motion study in two PHCs in Kansas and Louisiana. Research assistants observed a
      convenience sample of 246 child immunization visits to record distribution of the
      VISs and content and time of vaccine communication. Thirty percent of parents
      read below a ninth grade level, 53% had Medicaid insurance, and 56% were Black.
      VISs were given with every dose of vaccine administered in 89% of visits. Public
      health nurses (PHNs) frequently discussed potential vaccine side effects (91%),
      treatment of side effects (91%), and the vaccine schedule (93%).
      Contraindications were screened in 71% of visits. Benefits were discussed in 48%
      of visits and severe risks in 29%. The national Vaccine Injury Compensation
      Program (VICP) was never discussed. The immunization visits lasted for a mean of
      20 min. Vaccine communication of side effects, risks, benefits, screening for
      contraindications, and the next visit lasted for an average of 16 s for all
      vaccines. PHC compliance with mandated VIS distribution and practical vaccine
      communication was high. Room for improvement exists in discussion of benefits,
      serious risks, and the VICP.

PMID- 15144368
TI  - Maternal depression and anxiety and infant development: a comparison of foreign
      born and native-born mothers.
AB  - Studies that investigate infant and/or child development in families of depressed
      or anxious mothers do not include samples of foreign-born non-English-speaking
      mothers. This article describes a pilot study investigating infant development,
      maternal depression, and anxiety in comparison samples of native-born and foreign
      born mothers and children from Vietnam, Laos (Hmong), and the Democratic Republic
      of Congo. Maternal depression and anxiety were measured with the Hopkins Symptom
      Checklist-25, and the developmental status of children 0-25 months of age was
      measured with the Denver II. Foreign-born mothers were more anxious than native
      born mothers. Non-English-speaking foreign-born mothers were clinically depressed
      (1.83) and moderately anxious (1.62). Infants of native-born mothers and English
      speaking foreign-born mothers performed better on the Denver II than children of
      foreign-born non-English-speaking mothers. Infants and toddlers of non-English
      speaking mothers appear to be at high risk for delays during their first 25
      months of life. Public health nurses need to advocate for appropriate interpreter
      services and mental health resources for non-English-speaking mothers of young
      children. Developmental screening should reflect cultural variations in parental
      expectations of how and when children meet developmental milestones. Replication
      studies and investigation about the long-term development of this high-risk group
      of children are needed.

PMID- 15144369
TI  - Effectiveness of home visit falls prevention strategy for Taiwanese community
      dwelling elders: randomized trial.
AB  - The purpose of this research was to examine the effect of a multifactorial
      intervention to prevent falls by increasing self-efficacy to prevent falls,
      improving the knowledge of medication safety, and decreasing the number of
      environmental risks in older persons dwelling in the community. A sample of 120
      cognitively intact residents of this community who were 65 years of age and older
      were recruited into a two-group pretest-post-test experimental design and
      randomly assigned to an experimental group and a comparison group (60 in each
      group). The intervention was delivered, and data were collected during three home
      visits in a 4-month period. (1) Experimental subjects improved their fall self
      efficacy, environmental safety, and knowledge of medication safety significantly
      (p < 0.01) as compared with those in the comparison group at post-test; (2) the
      incidence of falls was reduced at post-test in both groups compared to pretest
      scores, and the falling was more serious in the comparison group at post-test
      compared to that in the experimental group. The results can help community health
      professionals to individualize their interventions to the specific needs of the
      elderly, thus helping to prevent falls among community-dwelling elders.

PMID- 15144370
TI  - Reliability and validity of the Chinese version of the Worry Scale.
AB  - This article presents the findings on the development and validation of a Chinese
      version of the Worry Scale (WS), a measure of worry about hypoglycemia. A
      previously developed 16-item WS was back-translated and applied to 117 Chinese
      diabetic patients living in Hong Kong. An iterative process of factor and item
      analyses identified a unidimensional 10-item Chinese WS (WS-10), which accounted
      for 57.15% of the total variance. Cronbach's alpha was 0.91. Strong correlation
      was demonstrated between the WS-10 and WS with 16 items (r = 0.97, p = 0.000).
      Comparing the level of worry about hypoglycemia between Type 1 and Type 2
      diabetic patients established a contrast-group validity of the WS-10 (p = 0.002).
      Criterion validity was established by correlating the WS-10 with the respondents'
      glycosylated hemoglobin (r = -0.29, p = 0.002). Test-retest reliability using
      intraclass correlation (ICC) was established, ICC(1, 1) = 0.68. As the clinical
      administration of this scale takes less than 5 min, the Chinese WS-10 offers a
      useful instrument to identify patients with high levels of worry about
      hypoglycemia for clinical and education interventions. It also provides public
      health nurses with a reliable and valid prepost measure of intervention
      effectiveness. The Chinese WS-10 will facilitate further research about the
      effects of worry concerning hypoglycemia on self-care behaviors with the Chinese
      populations.

PMID- 15144371
TI  - How much public health in public health nursing practice?
AB  - Public health nursing (PHN) practice is defined by an emphasis on population
      health issues rather than individually focused clinical interventions, but the
      actual scope and focus of PHN practice have not been well documented. The purpose
      of this survey was to investigate the practice activities, priorities, and
      education of public health nurses in California. Public health nurses in five
      counties were surveyed about interventions targeted at individual-family,
      community, and system levels. Summary scales (range: 1-4) were created to measure
      self-rated PHN activity, importance, and education at each level. Staff were most
      likely to perform individual-family level interventions (mean score, m=2.55),
      followed by community (m=1.86) and system-level interventions (m=1.46). Managers
      rated individual-family level interventions as most important (m=2.91) and
      community-level interventions (m=2.42) as more important than those at the system
      level (m=1.99). Individually focused case management was the most frequently
      performed and highly valued intervention. Staff and manager-directors deemed
      individual-family interventions as the area in which public health nurses were
      best educated, followed by community and then system interventions. Results
      indicate that the population health focus of public health nursing is not
      reflected in the practice activities, management priorities, or educational
      preparation of public health nurses.

PMID- 15144372
TI  - Public health nurses' perspectives on collaborative partnerships in South Africa.
AB  - The importance of partnerships and collaborations between different stakeholders
      in order to achieve health objectives are increasingly recognized. This article
      aims to: (1) highlight the importance of establishing partnerships and coalitions
      to achieve health goals; (2) consider the benefits and costs of such
      collaborations; and (3) identify the conditions which facilitate effective
      partnerships, from the perspective of nurses working within collaborative
      ventures in South Africa. A survey of these nurses was undertaken to consider
      their perceptions of the likely returns from investments in collaborative working
      and the extent of the relationship between the participation incentives and
      difficulties encountered. By examining their perceptions to a number of facets of
      partnership fostering, the article has elaborated on the meaning of collaboration
      and its rationale, and highlighted the conditions necessary for the success of
      community partnerships (CPs). The study has also demonstrated the feeling that
      CPs are beneficial with increased satisfaction along many operational parameters.
      Working to a shared agenda requires a "give and take attitude" among the
      stakeholders, designed to produce an outcome that merges multiple and new
      insights and directions for action, as well as the combined power foundation to
      do so.

PMID- 15144373
TI  - The evolution of the community health nurse practitioner in Korea.
AB  - Community health nursing in Korea has undergone dramatic changes since 1980.
      These changes arose through the efforts of Mo Im Kim, an internationally known
      leader in Korean nursing, and colleagues who successfully worked to establish a
      national community health nurse practitioner program. This article will review
      these changes with the aim of describing the evolutionary process that culminated
      in a community health care system that is meeting the needs of Korean citizens
      who live in rural and isolated areas. The authors believe that the evolution of
      the community health nurse practitioner in Korea provides a paradigm that can
      serve as a model for other countries. Health care in Korea is organized
      differently than that in the United States. However, the plan, process, and
      political activism can be used for community and public health nursing change in
      the United States. The information contained in this article is based upon
      interviews with Mo Im Kim and 20 of her colleagues and associates. Interviewees
      were selected using a "snowball" sampling technique. Additional data were derived
      from various professional and personal documents of these individuals. The first
      author conducted the interviews in both Korea and in the United States.

PMID- 15144375
TI  - Expression profiling of phyB mutant demonstrates substantial contribution of
      other phytochromes to red-light-regulated gene expression during seedling de
      etiolation.
AB  - Different Arabidopsis phytochrome (phy) family members (phyA through phyE)
      display differential photosensory and/or physiological functions in regulating
      growth and developmental responses to light signals. To identify the genes
      regulated by phyB in response to continuous monochromatic red light (Rc) during
      the induction of seedling de-etiolation, we have performed time-course,
      microarray-based expression profiling of wild type (WT) and phyB null mutants.
      Comparison of the observed expression patterns with those induced by continuous
      monochromatic far-red light (FRc; perceived exclusively by phyA) in WT and phyA
      null-mutant seedlings suggests early convergence of the FRc and Rc photosensory
      pathways to control a largely common transcriptional network. phyB mutant
      seedlings retain a surprisingly high level of responsiveness to Rc for the
      majority of Rc-regulated genes on the microarray, indicating that one or more
      other phys have a major role in regulating their expression. Combined with the
      robust visible morphogenic phenotype of the phyB mutant in Rc, these data suggest
      that different members of the phy family act in organ-specific fashion in
      regulating seedling de-etiolation. Specifically, phyB appears to be the dominant,
      if not exclusive, photoreceptor in regulating a minority population of genes
      involved in suppression of hypocotyl cell elongation in response to Rc signals.
      By contrast, this sensory function is apparently shared by one or more other phys
      in regulating the majority Rc-responsive gene set involved in other important
      facets of the de-etiolation process in the apical region, such as cotyledon cell
      expansion.

PMID- 15144374
TI  - Expression and function of HD2-type histone deacetylases in Arabidopsis
      development.
AB  - HD2 (histone deacetylase) proteins are plant-specific histone deacetylases
      (HDACs). The Arabidopsis genome contains four HD2 genes, namely HD2A, HD2B, HD2C,
      and HD2D. We have previously demonstrated that HD2A, HD2B, and HD2C can repress
      transcription directly by targeting to promoters in planta. Here, we show that
      the N-terminal conserved motif (EFWG) and histidine 25 (H25), a potential
      catalytic residue, were important for the gene repression activity of HD2A. In
      situ hybridization indicated that HD2A, HD2B, and HD2C were expressed in ovules,
      embryos, shoot apical meristems, and primary leaves. Furthermore, all three genes
      were strongly induced during the process of somatic embryogenesis. HD2D mRNA was
      only detected in the stems and flowers with young siliques and may have adopted
      different functions. Using green fluorescent protein (GFP) fusions, we
      demonstrated that HD2A, HD2B, and HD2C accumulated in the nuclei of Arabidopsis
      cells. Overexpression of 35S::GFP-HD2A in transgenic Arabidopsis plants generated
      pleiotropic developmental abnormalities, including abnormal leaves, delayed
      flowering, and aborted seed development. The data showed that normal pattern of
      HD2 expression was essential for normal plant development and that HD2A, HD2B,
      and HD2C may be needed for embryogenesis and embryo development. Reverse
      transcriptase (RT)-PCR analysis revealed that a number of genes involved in seed
      development and maturation were repressed in the 35S::GFP-HD2A plants, supporting
      a role of HD2A in the regulation of gene expression during seed development.

PMID- 15144376
TI  - The nuclear factor HCF145 affects chloroplast psaA-psaB-rps14 transcript
      abundance in Arabidopsis thaliana.
AB  - The high chlorophyll fluorescence (hcf)145 mutant of Arabidopsis thaliana is
      specifically affected in photosystem (PS)I function as judged from spectroscopic
      analysis of PSII and PSI activity. The defect is because of a severe deficiency
      of PSI core subunits, whereas levels of the four outer antenna subunits of PSI
      were less reduced in hcf145. Pulse labelling of chloroplast proteins indicated
      that synthesis of the two largest PSI reaction-centre polypeptides, Psa
      (photosystem I subunit) A and PsaB, is significantly affected by the mutation. A
      comparison of stationary transcript levels with rates of transcription
      demonstrates that hcf145 induces a decreased stability and, probably,
      transcription of the tricistronic psaA-psaB-rps (small-subunit ribosomal
      protein)14 mRNA, which is generated by the plastid-encoded RNA polymerase.
      Translation inhibition experiments excluded translational defects as primary
      cause of impaired mRNA stability. Larger primary transcripts, which also contain
      sequences of the ycf3 (hypothetical chloroplast reading frame) gene located
      upstream of the psaA-psaB-rps14 operon and generated by the action of the nuclear
      encoded RNA polymerase, are not targeted by the mutation. Real-time reverse
      transcription (RT)-PCR analysis has successfully been applied to quantify defined
      intervals of the tricistronic transcript and it was established that the psaA
      region is less stable than the rps14 region in hcf145. The hcf145 gene has been
      mapped on the upper part of chromosome 5.

PMID- 15144377
TI  - Functional analyses of the flowering time gene OsMADS50, the putative SUPPRESSOR
      OF OVEREXPRESSION OF CO 1/AGAMOUS-LIKE 20 (SOC1/AGL20) ortholog in rice.
AB  - A late-flowering mutant was isolated from rice T-DNA-tagging lines. T-DNA had
      been integrated into the K-box region of Oryza sativa MADS50 (OsMADS50), which
      shares 50.6% amino acid identity with the Arabidopsis MADS-box gene SUPPRESSOR OF
      OVEREXPRESSION OF CO 1/AGAMOUS-LIKE 20 (SOC1/AGL20). While overexpression of
      OsMADS50 caused extremely early flowering at the callus stage, OsMADS50 RNAi
      plants exhibited phenotypes of late flowering and an increase in the number of
      elongated internodes. This confirmed that the phenotypes observed in the knockout
      (KO) plants are because of the mutation in OsMADS50. RT-PCR analyses of the
      OsMADS50 KO and ubiquitin (ubi):OsMADS50 plants showed that OsMADS50 is an
      upstream regulator of OsMADS1, OsMADS14, OsMADS15, OsMADS18, and Hd (Heading
      date)3a, but works either parallel with or downstream of Hd1 and O. sativa
      GIGANTEA (OsGI). These results suggest that OsMADS50 is an important flowering
      activator that controls various floral regulators in rice.

PMID- 15144378
TI  - Light induces phenylpropanoid metabolism in Arabidopsis roots.
AB  - Experiments have shown that many phenylpropanoid genes are highly expressed in
      light-grown Arabidopsis roots. Studies employing reporter gene constructs have
      indicated that the expression of these genes is localized not only to the
      lignifying root vasculature, but also to non-lignifying tissues, such as the root
      cortex, suggesting that the proteins encoded by these genes may be involved in
      aspects of phenylpropanoid metabolism other than lignification. Consistent with
      this hypothesis, roots of etiolated and soil-grown plants contain almost no
      soluble phenylpropanoids, but exposure to light leads to the accumulation of
      flavonoids, as well as high levels of coniferin and syringin (coniferyl and
      sinapyl-4-O-glycosides), compounds not previously reported to be accumulated in
      Arabidopsis. To elucidate the mechanism by which light induces root secondary
      metabolism, extracts of mutants defective in light perception and light responses
      were analyzed for phenylpropanoid content. The results of these assays showed
      that phytochrome (PHY)B and cryptochrome (CRY)2 are the primary photoreceptors
      involved in light-dependent phenylpropanoid accumulation, and that the hypocotyl
      elongated (HY5) transcription factor is also required for this response. The
      presence of phenylpropanoids in etiolated roots of cop (constitutively
      photomorphogenic)1, cop9, and det (de-etiolated)1 mutants indicate that the
      corresponding wild-type genes are required to repress root phenylpropanoid
      biosynthesis in the absence of light. Biochemical analysis of root cell walls and
      analysis of phenylpropanoid gene expression suggest that coniferin and syringin
      accumulation may be the result of both increased biosynthesis and decreased
      conversion of these compounds into other phenylpropanoid end products. Finally,
      our data suggest that the accumulation of coniferin, syringin, and flavonoids in
      Arabidopsis roots is a high-irradiance response (HIR), and suggest that
      comparative analysis of light- and dark-grown Arabidopsis roots may provide new
      insights into both phenylpropanoid biosynthesis and light signaling in plants.

PMID- 15144379
TI  - A novel regulatory pathway of sulfate uptake in Arabidopsis roots: implication of
      CRE1/WOL/AHK4-mediated cytokinin-dependent regulation.
AB  - Cytokinin is an adenine derivative plant hormone that generally regulates plant
      cell division and differentiation in conjunction with auxin. We report that a
      major cue for the negative regulation of sulfur acquisition is executed by
      cytokinin response 1 (CRE1)/wooden leg (WOL)/Arabidopsis histidine kinase 4
      (AHK4) cytokinin receptor in Arabidopsis root. We constructed a green fluorescent
      protein (GFP) reporter system that generally displays the expression of the high
      affinity sulfate transporter SULTR1;2 in Arabidopsis roots. GFP under the control
      of SULTR1;2 promoter showed typical sulfur responses that correlate with the
      changes in SULTR1;2 mRNA levels; accumulation of GFP was induced by sulfur
      limitation (-S), but was repressed in the presence of reduced sulfur compounds.
      Among the plant hormones tested, cytokinin significantly downregulated the
      expression of SULTR1;2. SULTR1;1 conducting sulfate uptake in sultr1;2 mutant was
      similarly downregulated by cytokinin. Downregulation of SULTR1;1 and SULTR1;2 by
      cytokinin correlated with the decrease in sulfate uptake activities in roots. The
      effect of cytokinin on sulfate uptake was moderated in the cre1-1 mutant,
      providing genetic evidence for involvement of CRE1/WOL/AHK4 in the negative
      regulation of high-affinity sulfate transporters. These data demonstrated the
      physiological importance of the cytokinin-dependent regulatory pathway in
      acquisition of sulfate in roots. Our results suggested that two different modes
      of regulation, represented as the -S induction and the cytokinin-dependent
      repression of sulfate transporters, independently control the uptake of sulfate
      in Arabidopsis roots.

PMID- 15144380
TI  - Heterosis in the freezing tolerance of crosses between two Arabidopsis thaliana
      accessions (Columbia-0 and C24) that show differences in non-acclimated and
      acclimated freezing tolerance.
AB  - Heterosis is broadly defined as the increased vigour of hybrids in comparison to
      their parents. In the model plant Arabidopsis thaliana, a significant heterosis
      effect on leaf-freezing tolerance was observed in the F(1) generation of a cross
      between the accessions Columbia-0 (Col) and C24. Parental Col plants were
      significantly more freezing-tolerant than C24 plants in both the acclimated and
      non-acclimated (NA) states. Mid-parent heterosis was observed in the F(1) plants,
      both in the basic tolerance of non-adapted plants and in freezing tolerance after
      cold acclimation. Best-parent heterosis, on the other hand, was only found after
      cold acclimation. The heterosis effect was reduced in the F(2) populations such
      that only mid-parent heterosis was evident. The leaf content of soluble sugars
      (fructose (Fru), glucose (Glc), sucrose (Suc) and raffinose (Raf)) increased
      dramatically in the F(1) plants after cold acclimation as compared to the
      parental lines. The content of proline (Pro), however, was only moderately
      increased in the F(1) plants under the same conditions. Correlation analyses
      showed that only Raf content was consistently related to leaf-freezing tolerance
      in both the acclimated and NA states. A quantification of mRNA levels in leaves
      of parental and F(1) lines using quantitative real-time RT-PCR showed no clear
      indication for an involvement of the investigated genes (CBF (C-repeat binding
      factor)1, CBF2, (cold-regulated protein (COR) 6.6, COR15a, COR15b, COR47 and
      COR78) in the heterosis effect.

PMID- 15144381
TI  - Involvement of MEK1 MAPKK, NTF6 MAPK, WRKY/MYB transcription factors, COI1 and
      CTR1 in N-mediated resistance to tobacco mosaic virus.
AB  - The tobacco N gene, a member of the Toll-interleukin 1 homology region/nucleotide
      binding site/leucine-rich repeat (TIR-NBS-LRR) class of resistance (R) genes,
      confers resistance to tobacco mosaic virus (TMV). We used a candidate gene
      approach to identify known defense genes that were also involved in N signaling.
      The requirement for these genes was determined by downregulating their expression
      using the well-established tobacco rattle virus (TRV)-based virus-induced gene
      silencing (VIGS). Silencing of genes encoding a mitogen-activated protein kinase
      (MAPK) NTF6/NRK1, or an MAPK kinase (MAPKK) MEK1/NQK1, attenuated N-mediated
      resistance to TMV. We also found that N resistance is compromised in plants in
      which expression of WRKY1-WRKY3 and MYB1 transcription factors were
      downregulated. In addition, suppression of jasmonic acid (JA) signaling component
      COI1 ortholog affected N function. However, downregulation of expression of CTR1
      ortholog leads to more rapid hypersensitive response (HR). The involvement of
      these genes in N- and other R-gene-mediated defense provides further evidence for
      the convergence of downstream signaling pathways of different R genes.

PMID- 15144382
TI  - Drought tolerance established by enhanced expression of the CC-NBS-LRR gene,
      ADR1, requires salicylic acid, EDS1 and ABI1.
AB  - An activation-tagged allele of activated disease resistance 1 (ADR1) has
      previously been shown to convey broad spectrum disease resistance. ADR1 was found
      to encode a coiled-coil (CC)-nucleotide-binding site (NBS)-leucine-rich repeat
      (LRR) protein, which possessed domains of homology with serine/threonine protein
      kinases. Here, we show that either constitutive or conditional enhanced
      expression of ADR1 conferred significant drought tolerance. This was not a
      general feature of defence-related mutants because cir (constitutive induced
      resistance)1, cir2 and cpr (constitutive expressor of PR genes)1, which
      constitutively express systemic acquired resistance (SAR), failed to exhibit this
      phenotype. Cross-tolerance was not a characteristic of adr1 plants, rather they
      showed increased sensitivity to thermal and salinity stress. Hence, adr1
      activated signalling may antagonise some stress responses. Northern analysis of
      abiotic marker genes revealed that dehydration-responsive element (DRE)B2A but
      not DREB1A, RD (response to dehydration)29A or RD22 was expressed in adr1 plant
      lines. Furthermore, DREB2A expression was salicylic acid (SA) dependent but NPR
      (non-expressor of PR genes)1 independent. In adr1/ADR1 nahG (naphthalene
      hydroxylase G), adr1/ADR1 eds (enhanced disease susceptibility)1 and adr1/ADR1
      abi1 double mutants, drought tolerance was significantly reduced. Microarray
      analyses of plants containing a conditional adr1 allele demonstrated that a
      significant number of the upregulated genes had been previously implicated in
      responses to dehydration. Therefore, biotic and abiotic signalling pathways may
      share multiple nodes and their outputs may have significant functional overlap.

PMID- 15144383
TI  - Differential mRNA translation contributes to gene regulation under non-stress and
      dehydration stress conditions in Arabidopsis thaliana.
AB  - Translational regulation was evaluated for over 2000 genes by measurement of the
      proportion of individual mRNA species in polysomal (PS) complexes in leaves of
      non-stressed and moderately dehydration-stressed Arabidopsis. The amount of each
      mRNA in polysomes ranged from 23 to 97% in non-stressed leaves and was
      significantly reduced for a large portion of the genes (71%) in response to
      dehydration. The effect of dehydration on translational status varied extensively
      between mRNA species. Sixty per cent of the dehydration-inducible mRNAs with
      twofold or greater increase in abundance maintained PS levels in response to
      water-deficit stress, while 40% showed impaired ribosome loading (RL). PS
      association declined significantly for 92% of the mRNAs that displayed a strong
      decrease in abundance, indicating a relationship between translation and
      decreased gene transcription and/or mRNA stability. Interestingly, many mRNAs
      that encode proteins of similar biological function displayed coordinate
      translational regulation. Thus, the abundance of PS mRNA may provide a more
      accurate estimate of gene expression than total cellular mRNA because of
      extensive differential translational regulation.

PMID- 15144384
TI  - An intragenic tandem duplication in a transcriptional regulatory gene for
      anthocyanin biosynthesis confers pale-colored flowers and seeds with fine spots
      in Ipomoea tricolor.
AB  - While the wild-type morning glory (Ipomoea tricolor) displays bright-blue flowers
      and dark-brown seeds, its spontaneous mutant, Blue Star, carrying the mutable
      ivory seed-variegated (ivs-v) allele, exhibits pale-blue flowers with a few fine
      blue spots and ivory seeds with tiny dark-brown spots. The mutable allele is
      caused by an intragenic tandem duplication of 3.3 kbp within a gene for
      transcriptional activator containing a basic helix-loop-helix (bHLH) DNA-binding
      motif. Each of the tandem repeats is flanked by a 3-bp sequence AAT, indicating
      that the 3-bp microhomology is used to generate the tandem duplication. The
      transcripts in the pale-blue flower buds of the mutant contain an internal 583-bp
      tandem duplication that results in the production of a truncated polypeptide
      lacking the bHLH domain. The mRNA accumulation of most of the structural genes
      encoding enzymes for anthocyanin biosynthesis in the flower buds of the mutant
      was significantly reduced. The transcripts identical to the wild-type mRNAs for
      the transcriptional activator were present abundantly in blue spots of the
      variegated flowers, whereas the transcripts containing the 583-bp tandem
      duplication were predominant in the pale-blue background of the same flowers. The
      flower and seed variegations studied here are likely to be caused by somatic
      homologous recombination between an intragenic tandem duplication in the gene
      encoding a bHLH transcriptional activator for anthocyanin biosynthesis, whereas
      various flower variegations are reported to be caused by excision of DNA
      transposons inserted into pigmentation genes.

PMID- 15144385
TI  - A modified viral satellite DNA that suppresses gene expression in plants.
AB  - DNAbeta is a type of single-stranded (ss) circular satellite DNA found in
      association with monopartite-genome begomoviruses, such as Tomato yellow leaf
      curl China virus isolate Y10 (TYLCCNV-Y10). Y10 DNAbeta is required for symptom
      expression in plants but depends on TYLCCNV-Y10 genomic DNA (DNA-A) for
      replication and encapsidation. When we converted DNAbeta into a gene-silencing
      vector (modified DNAbeta (DNAmbeta)) by replacing its C1 open-reading frame (ORF)
      with a multiple cloning site (MCS), it was replicated but no longer induced
      symptoms in association with TYLCCNV-Y10 DNA-A, so allowing the effects of gene
      inserts to be recognized easily. Insertion into DNAmbeta of sequences from any of
      the three host genes (proliferating cell nuclear antigen (PCNA), phytoene
      desaturase (PDS), and sulfur (Su)), or from a transgene (green fluorescent
      protein (GFP)), resulted in silencing of the cognate gene in Nicotiana
      benthamiana. The silencing persisted for more than a month and was associated
      with decreased levels of mRNA of the gene targeted. Although DNAmbeta probably
      does not enter meristematic tissue, the PCNA gene could be silenced there.
      DNAmbeta was an effective silencing vector in tested N. glutinosa, N. tabacum
      Samsun (NN or nn), and Lycopersicon esculentum plants, and was able to silence
      two genes simultaneously. This satellite DNA vector-based form of virus-induced
      gene silencing (VIGS) promises to be applicable to other begomovirus/DNAbeta
      systems, which are recently reported to occur in several dicotyledonous crop
      species, thereby providing a powerful approach to gene discovery and the analysis
      of gene function in these crops.

PMID- 15144386
TI  - In silico screening of a saturated mutation library of tomato.
AB  - A comprehensive mutant population is a basic resource for exploring gene
      function. We developed an isogenic tomato 'mutation library' in the genetic
      background of the inbred variety M82. A total of 13 000 M(2) families, derived
      from EMS (ethyl methane sulfonate) and fast-neutron mutagenesis, were visually
      phenotyped in the field and categorized into a morphological catalog that
      includes 15 primary and 48 secondary categories. Currently, 3417 mutations have
      been cataloged; among them are most of the previously described phenotypes from
      the monogenic mutant collection of The Tomato Genetics Resource Center, and over
      a thousand new mutants, with multiple alleles per locus. The phenotypic database
      indicates that most mutations fall into more than a single category
      (pleiotropic), with some organs such as leaves more prone to alterations than
      others. All data and images can be searched and accessed in the Solanaceae Genome
      Network (SGN) on a site called 'The Genes That Make Tomatoes'
      (http://zamir.sgn.cornell.edu/mutants/).

PMID- 15144388
TI  - Photoallergic contact dermatitis.
AB  - PURPOSE: To determine whether photoallergic contact dermatitis is as uncommon as
      it is usually considered to be and to review the associated clinical features.
      METHODS: We reviewed the literature on photoallergic reactions induced by the
      topical contact of the skin with a chemical in the presence of, or followed by,
      exposure to UV or visible light. Some of the more recently observed photo
      allergens and those presenting special clinical features are discussed. RESULTS:
      The literature cites several topical substances that give rise to photoallergic
      contact dermatitis, some of them only exceptionally but others quite frequently.
      The clinical features are not always those of a eczematous eruption, and several
      parts of the body may be affected. CONCLUSIONS: Many topical photoallergic
      culprits have been reported in the literature, the most important of which are
      sunscreen agents and, recently, non-steroidal anti-inflammatory agents (NSAIDs).
      Not at all exceptional is the occurrence of photoaggravation and recurrent
      transient or even persistent light reactions on previously exposed as well as non
      exposed areas (often sparing the original application site), particularly with
      the NSAID ketoprofen. Moreover, cross-reactions with chemically-related as well
      as non-chemically related molecules are common. The potentially misleading
      clinical features observed in some cases, the diversity of the casual substances
      identified, and the low frequency with which photopatch testing is carried out in
      general indicate that the occurrence of photoallergic contact dermatitis might
      well be underestimated.

PMID- 15144391
TI  - Ground-level solar spectral irradiance in Glasgow: an inter-comparison of two
      sites.
AB  - BACKGROUND: Solar spectral radiometry presents significant challenges to produce
      accurate and reproducible data. To investigate the reliability of the
      measurements, several inter-comparisons have been set up. Although these are
      useful, their main drawback is that equipment must be dismantled and transported
      to a common site and re-calibrated. METHODS: In this study, an inter-comparison
      has been performed of two spectroradiometers that are located 3 miles apart some
      30 m above sea level. These two systems have operated using different calibration
      techniques. Data were compared on clear days, to minimise actual differences in
      ultraviolet irradiation. RESULTS: There were substantial differences at some
      individual wavelength points, but overall the mean difference of results at 5 nm
      intervals on an individual scan from the two systems agreed to within 11%. If the
      data were used to compute the erythemal irradiance, the differences were reduced
      to 4%. CONCLUSION: This study demonstrates both the limitations and the level of
      reliability that might be expected from these systems operating under careful
      scientific supervision.

PMID- 15144390
TI  - Gene expression profiling of in vivo UVB-irradiated human epidermis.
AB  - BACKGROUND: Several recent studies have employed microarray profiling to study
      UVB-regulated gene expression in human skin. These studies are all based on UV
      irradiated cultured cells that differ substantially from the intact tissues they
      are supposed to imitate. The purpose of the present study was to analyze the
      differential expression of UVB-regulated genes in intact human epidermis
      following in vivo UV irradiation. METHODS: The forearms of human volunteers were
      exposed to 4 MED of UVB in vivo, followed by removal of epidermal samples from
      exposed and non-exposed areas after 24 h. RNA samples were analyzed using
      oligonucleotide microarray (Affymetrix) technology analyzing 12 500 genes
      simultaneously. Verification of selected genes was performed by semi-quantitative
      reverse transcriptase polymerase chain reaction. RESULTS: Gene expression
      patterns clearly distinguished UV-exposed epidermis from unexposed skin.
      Classification of these genes into functional categories revealed that several
      biological processes are globally affected by UVB. Significant changes were seen
      in more than 800 genes. CONCLUSION: Human intact epidermis responds to a single
      low dose of in vivo UVB irradiation by differential regulation of numerous genes.
      Our results illustrate the power of global gene expression analysis of human
      epidermis to identify molecular pathways involved in UV-induced photodamage.

PMID- 15144392
TI  - Photodynamic therapy of interdigital mycoses of the feet with topical application
      of 5-aminolevulinic acid.
AB  - BACKGROUND: Findings of in vitro studies have demonstrated that dermatophytes and
      yeasts can be effectively photosensitized after topical delivery of 5
      aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT),
      seems to lack mutagenic activity and hazard of selection of drug-resistant
      strains. METHODS: Twenty percent ALA preparation in Eucerin cream was applied
      under an occlusive dressing to skin lesions of nine patients with clinical and
      microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions
      were irradiated with 75 J/cm(2) of broad-band red light. Interdigital lesions of
      the other foot served as control (treated with only light or only ALA). After 7
      days from the first treatment, no further treatment was delivered if lesions were
      not clinically evident and direct microscopic examination was negative.
      Otherwise, three additional weekly treatments were delivered. Four weeks after
      the last treatment, patients had a final follow-up clinical and laboratory
      examination. RESULTS: Clinical and microbiological recovery was seen in six out
      of nine patients after one (four cases) or four (two cases) treatments. However,
      after 4 weeks, recurrences were seen in four patients. Overall tolerability was
      always good. CONCLUSION: Under the conditions employed in the present study, ALA
      PDT had good therapeutic effects on interdigital mycosis of the feet. However,
      recurrences were quick. In vivo environmental conditions, i.e. temperature,
      humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA
      and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition,
      the irregular tridimensional shape of this peculiar anatomical area could lead to
      a non-uniform delivery of light and/or ALA cream. However, the present results
      can stimulate further studies on the PDT of superficial skin mycoses.

PMID- 15144393
TI  - Different low doses of broad-band UVA in the treatment of morphea and systemic
      sclerosis.
AB  - BACKGROUND: Numerous treatment modalities, some with potentially hazardous side
      effects, are currently used for morphea (M) and systemic sclerosis (SS) with
      limited success. Low-dose ultraviolet A (UVA) phototherapy (20 J/cm(2)) was found
      to be highly effective for sclerotic patches, even in patients with advanced and
      rapidly evolving lesions. OBJECTIVE: To determine the effectiveness of different
      low doses of UVA in treating patients with M and SS. METHODS: Sixty-three
      patients complaining of M and 15 patients complaining of SS received 20 sessions
      of UVA (320-400 nm) each. Patients were divided randomly into three groups that
      received 5, 10 and 20 J/cm(2), with cumulative UVA doses of 100, 200, and 400
      J/cm(2), respectively. The efficacy of therapy was judged clinically (by
      sequential inspection and palpation) and histopathologically by morphometry in M
      cases. RESULTS: Obvious clinical improvement, with no comparable differences
      between various low UVA doses, was noted in patients with M and SS, accompanied
      by histopathological changes towards normalization of collagen. CONCLUSIONS:
      After 20 sessions, it appears that lower doses of UVA (5, 10 J/cm(2)) are as
      beneficial as the relatively higher dose (20 J/cm(2)) in the treatment of M and
      SS.

PMID- 15144394
TI  - PIBIDS syndrome (trichothiodystrophy type F) and skin cancer: an exceptional
      association.

PMID- 15144395
TI  - Pathological and molecular biological aspects of the renal epithelial neoplasms,
      up-to-date.
AB  - Renal neoplasms are not necessarily high in frequency, but they are
      characteristic in their heterogeneity and occasional association with systemic
      familial tumor syndromes and phacomatoses (e.g. clear cell renal cell carcinoma
      and von Hippel-Lindau disease, Wilms tumor and aniridia, genitourinary
      malformation and mental retardation (so-called, WAGR syndrome), and
      angiomyolipoma and tuberous sclerosis). Physicians and pathologists should take
      note of these syndromes and associated renal neoplasms because they have provided
      important clues to elucidate the mechanism of tumorigenesis concerning cancer
      suppressor genes. This review aims to present recent classification of renal
      parenchymal neoplasms based on their molecular biological characteristics, and
      future problems yet to be clarified.

PMID- 15144397
TI  - Immunohistochemically detectable Cdx2 is present in intestinal phenotypic
      elements in early gastric cancers of both differentiated and undifferentiated
      types, with no correlation to non-neoplastic surrounding mucosa.
AB  - It has previously been reported that Cdx2 is the useful prognostic and intestinal
      phenotypic marker in advanced gastric cancers (GC). In this study, Cdx2
      expression and phenotype in early GC and non-neoplastic surrounding mucosa were
      examined. A total of 130 early GC (70 intramucosal and 60 submucosally invasive
      cancers) histologically and phenotypically were evaluated. The expression of Cdx2
      was assessed by immunohistochemistry. The lesions were phenotypically divided
      into 44 gastric (G), 42 gastric and intestinal mixed (GI), 30 intestinal (I), and
      14 null (N) types, independent of the histological classification. Most of the
      early GC were Cdx2-positive, nuclear staining being strongly associated with
      intestinal phenotypic expression. Early differentiated cancers tended to feature
      both Cdx2 and intestinal phenotypic expression, while their undifferentiated
      counterparts were more likely to demonstrate only gastric phenotypic expression
      (P < 0.05). The phenotypes of six intramucosal microcarcinomas did not correlate
      with those of adjacent normal glands. These data suggest that Cdx2 is expressed
      in the very early stage of gastric carcinogenesis in association with the shift
      from gastric to intestinal phenotypic expression. This appears to occur in
      differentiated cancers at an earlier stage than in undifferentiated ones, and may
      be linked to suppression of expansion of malignant cells.

PMID- 15144396
TI  - Accumulation of MDM2 in pleomorphic xanthoastrocytomas.
AB  - The molecular genetic basis and the tumorigenic mechanism of pleomorphic
      xanthoastrocytoma (PXA) still remain to be elucidated. The amplification of the
      mdm2 gene and accumulation of the MDM2 protein, which is considered to be one of
      the major cellular regulators of p53-mediated cell growth control, were studied
      in eight specimens of PXA obtained from five patients. All of the PXA samples
      showed at least focal immunopositivity for MDM2. However, none of the samples
      showed mdm2 gene amplification. These results suggest that accumulation of MDM2
      without gene amplification may be one of the major molecular events occurring in
      the tumorigenesis of PXA.

PMID- 15144398
TI  - Bidirectional gastric differentiation in cellular mucin phenotype (foveolar and
      pyloric) in serrated adenoma and hyperplastic polyp of the colorectum.
AB  - This study examined whether gastric pyloric gland-type mucin is expressed in
      serrated adenoma (SA) and in hyperplastic polyp (HP) of the colorectum, and
      whether cellular position-based gastric differentiation is observed in these
      lesions as previously hypothesized. Immunostaining was performed for MUC6 and
      alpha-linked GlcNAc residue (pyloric gland-type mucin markers), human gastric
      mucin (HGM; foveolar-type mucin marker) and Ki-67 (proliferating cell marker) for
      31 SA, 22 HP, 21 traditional tubular adenoma (TA) and 20 hyperplastic nodule
      (HN). MUC6 showed varying expression in SA, 22/31 (71.0%); HP, 15/22 (68.2%); TA,
      2/21 (9.5%); and HN, 0/20 (0%) with significantly higher frequencies in SA and HP
      compared to those in TA and HN. The alpha-linked GlcNAc residue was found only in
      SA (3/31, 9.7%) and in HP (2/22, 9.1%). In SA and HP, HGM was typically expressed
      in the entire crypt length, but some reduction in expression was shown in the
      basal crypt portion below the proliferative zone. MUC6 and alpha-linked GlcNAc
      residues were expressed in the basal crypt portion below or below and including
      proliferative zone. These data demonstrate that SA and HP show bidirectional
      gastric (foveolar and pyloric gland) differentiation with respect to mucin
      cellular phenotype and the potential for cellular position-based differentiation,
      which mimics the gastric antral mucosa.

PMID- 15144399
TI  - Histidine decarboxylase expression in pancreatic endocrine cells and related
      tumors.
AB  - Histidine decarboxylase (HDC) is an enzyme for decarboxylating l-histidine to
      histamine and is expressed in various types of cells including neuroendocrine
      tumors. Recent findings have demonstrated a high percentage of HDC
      immunoreactivity in many neuroendocrine tumors, including carcinoid tumors, small
      cell carcinomas of the lung, pheochromocytomas, and medullary carcinomas of the
      thyroid. HDC immunostaining was applied to pancreatic islet cells and related
      tumors to explore possible expression of HDC as a wide spectrum marker for
      neuroendocrine differentiation. A total of 24 cases (22 pancreatic endocrine
      neoplasms, one small cell carcinoma of the pancreas, and one mixed exocrine
      endocrine carcinoma) along with normal pancreatic tissue were immunostained with
      the anti-HDC antibody. In a normal pancreas, a double immunostaining revealed
      possible colocalization of HDC with glucagon- or insulin-positive cells in the
      islets. Seventeen of 22 pancreatic endocrine neoplasms (77%) were found to be
      positive for HDC, and no distinct relation to hormonal activity was observed. One
      small cell carcinoma was strongly positive to HDC. One non-functional tumor with
      mixed exocrine and endocrine components showed a diffuse positive immunostaining
      for HDC, and some neoplastic glucagon- or somatostatin (SRIF)-positive cells
      coexpressed HDC. In conclusion, we demonstrated that the majority of pancreatic
      endocrine tumors expressed HDC, and we suggest that HDC is a wider new marker for
      neuroendocrine differentiation.

PMID- 15144400
TI  - Abnormalities in chromosome 17 and p53 in lung carcinoma cells detected by
      fluorescence in situ hybridization.
AB  - The value of fluorescence in situ hybridization (FISH) as an aid to deciding the
      prognosis for lung carcinoma patients, comparing quantitatively the signal from
      the p53 gene (17p13.1) on chromosome 17, was studied. A dual-labeling technique
      was used, using probes for the centromeric region of chromosome 17 and for the
      p53 gene locus. FISH was used on frozen sections of 68 surgically resected lung
      carcinoma (20 adenocarcinoma; 37 squamous cell carcinoma; 11 large, small, and
      other cell carcinoma). Hybridization signals were counted for 100-200 interphase
      nuclei per specimen using a Zeiss confocal laser scanning microscope (Carl Zeiss,
      Oberkochen, Germany) equipped with a bandpass filter for diaminophenolindole and
      a longpass filter for rhodamine. Clinicopathologic data were evaluated using the
      Statistical Analysis System. Chromosome 17 polysomy (three or more signals) was
      greater in poorly differentiated than in well-differentiated lung carcinoma (P <
      0.05). p53 deletion correlated with p53 immunostaining (P < 0.05). Thus, analysis
      by FISH using DNA probes for chromosome 17 and p53 may be of some, albeit
      limited, value in determination of prognosis.

PMID- 15144401
TI  - Ovarian mucinous borderline tumors of intestinal type without intraepithelial
      carcinoma: are they still tumors of low malignant potential?
AB  - The purpose of this study was to clarify whether ovarian intestinal-type mucinous
      borderline tumors without intraepithelial carcinoma should still be considered
      tumors of low malignant potential. Fifty-five intestinal-type mucinous borderline
      tumors without intraepithelial carcinoma in which a section had been taken for
      each 2 cm or less of the tumor's greatest diameter were selected. The
      International Federation of Gynecology and Obstetrics' stage and follow-up data
      of each case were examined. All 55 patients had stage I disease (including one
      with pseudomyxoma peritonei of superficial organizing type, according to Lee and
      Scully's classification). No patient had metastases or died from the tumor,
      although in one patient who underwent cystectomy, the disease recurred in the
      remaining ovary 5 years after surgery. However, the patient was alive and well
      after undergoing salpingo-oophorectomy. The patient with pseudomyxoma peritonei
      had no recurrence and did not die from the tumor. These findings indicated that
      intestinal-type mucinous borderline tumors, in which intraepithelial carcinoma
      has been ruled out with adequate histological sampling, are benign tumors, not
      tumors of low malignant potential. It is proposed here that these tumors should
      be designated as high-grade mucinous adenoma. Unilateral salpingo-oophorectomy is
      the recommended treatment because cystectomy alone may allow local recurrence in
      the remaining ovary.

PMID- 15144402
TI  - Analysis of mucin, p53 protein and Ki-67 expressions in gastric differentiated
      type intramucosal neoplastic lesions obtained from endoscopic mucosal resection
      samples: a proposal for a new classification of intramucosal neoplastic lesions
      based on nuclear atypia.
AB  - There are differing views between Western and Japanese pathologists on the use of
      histological criteria to classify gastrointestinal tumors. It is therefore a
      priority to create a new histological classification of the stomach in order to
      resolve the confusion. Expression patterns were examined of mucin (MUC2, CD10,
      MUC5AC, pyloric gland-type mucin), p53 protein, and Ki-67 in tumor cells
      according to the following new classification system for differentiated-type
      intramucosal neoplastic lesions of the stomach, based on nuclear atypia:
      borderline neoplasia (adenoma (including dysplasia), indefinite tumor of adenoma
      or low-grade cancer, and low-grade cancer) and definite carcinoma (intermediate
      cancer, and high-grade cancer). The resulting grades were: adenoma, 23;
      indefinite tumor for adenoma or low-grade cancer, 6; low-grade cancer, 28;
      intermediate cancer, 48; high-grade cancer, 20. While the frequency of intestinal
      type borderline neoplasias was higher than that of definite carcinomas, the mixed
      type of definite carcinomas occurred with higher frequency than borderline
      neoplasias. The p53 protein overexpression and the Ki-67-positive rate increased
      with an increase in the grade assigned according to the new classification. The
      correlated expression levels of p53 protein, Ki-67, and various mucins, support
      the conclusion that this classification of intramucosal neoplastic lesions is
      useful for obtaining a consensus diagnosis of gastric intramucosal neoplasia
      between pathologists and gastrointestinal clinicians.

PMID- 15144403
TI  - Solitary fibrous tumor arising in gastric serosa.
AB  - The solitary fibrous tumor (SFT) of peritoneum, especially arising in gastric
      serosa, is extremely rare. A case of SFT arising in gastric serosa of a 70-year
      old man is reported. On abdominal computed tomography scan, an approximate 8.0 x
      5.3 cm-sized solid mass with multiple nodular calcifications was noted in the
      omentomesentery of right upper abdomen, which was abutting to the gastric antral
      wall. At laparotomy the tumor was tightly attached to the gastric serosa and was
      completely excised by wedge resection of the stomach. The cut surfaces of the
      tumor were pale brown to pale yellow, firm, with multifocal yellowish, gritty,
      stony-hard nodules and cystic changes. Microscopically, the tumor was composed of
      mildly cellular benign-appearing spindle-shaped cells and bands of hyalinized
      collagen in varying proportions. The tumor revealed predominantly sclerosing
      pattern with extensive hyalinized fibrosis and multifocal dystrophic
      calcifications. The tumor was mainly located at the gastric serosa and subserosa,
      and its growth pattern was expansile with entrapping of muscularis propria and
      submucosa in the periphery of the tumor. By immunohistochemistry, the tumor cells
      were diffusely positive for CD34 and vimentin but negative for cytokeratin,
      desmin, smooth muscle actin, CD99 and c-kit. Although its occurrence is rare, SFT
      should be considered in the differential diagnosis of mesenchymal tumors of the
      stomach.

PMID- 15144404
TI  - Liver metastasis from rectal cancer with prominent intrabile duct growth.
AB  - Intrabiliary growth of liver metastases from colorectal cancer has rarely been
      studied. A surgically resected case of a metastatic liver tumor with prominent
      intrabiliary growth derived from rectal cancer is reported. The patient was a 62
      year-old man who had received a low anterior resection for rectal cancer in March
      2000. He was re-admitted due to obstructive jaundice in January 2003, and was
      diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary
      tumor extending from the intrahepatic bile duct of segment II to the common
      hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI,
      and an extrahepatic bile duct resection with reconstruction of the biliary tract.
      In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in
      diameter in segments II and VI, respectively, and an intrabiliary tumor
      originating from the main tumor in segment II extended to the common hepatic
      duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to
      moderately differentiated adenocarcinoma, which showed the same histological
      features as the rectal cancer. The immunohistochemical findings strongly
      supported that these tumors, including the intrabiliary growth, were liver
      metastasis from the rectal cancer. The intrabiliary invasion and growth of
      metastatic liver tumors has generally been overlooked, notwithstanding their
      frequently observed biological behavior. The present case is informative, and
      further investigation into this type of metastatic liver tumor may be warranted.

PMID- 15144405
TI  - Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an
      adult.
AB  - A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare
      and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this
      study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)-like
      features, which produced difficulty in the differential diagnosis between
      sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor
      composed of poorly differentiated HCC, Edmondson's grade III, and more primitive
      components, which were embryonal and small cell undifferentiated components of HB
      like areas. The small undifferentiated cells surrounded HCC and the embryonal
      component of HB-like area, and revealed transition partly to areas of
      rhabdomyosarcoma. A small portion of chondrosarcoma was also noted.
      Immunohistochemical analysis showed that HCC and the embryonal component of HB
      like areas expressed alpha-fetoprotein (AFP) and cytokeratin 8. The small
      undifferentiated cells were negative for AFP but stained with cytokeratin 8 as
      well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is
      not certain whether small undifferentiated cells belong to hepatic progenitor
      cells or primitive mesenchymal cells. Polymerase chain reaction-single-strand
      conformation polymorphism analysis for beta-catenin mutation using
      microdissection revealed no mutation of any components. A review was undertaken
      of the cases previously reported as adult hepatoblastoma without detailed
      immunohistochemical study and consider many of them may be sarcomatoid HCC. These
      primitive and sarcomatoid components would be arising from the dedifferentiation
      process of HCC.

PMID- 15144406
TI  - Malignant transformation of atypical endometrial hyperplasia after progesterone
      therapy showing germ-cell tumor-like differentiation.
AB  - A 31-year-old woman was treated for atypical endometrial hyperplasia (AEH) with
      high-dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The
      AEH was found by repeated cytologic and histologic examinations to have
      completely disappeared with the therapy, but 3 years after her last follow up she
      required emergency surgery to treat severe genital bleeding. The hysterectomied
      uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid
      type. Minor AEH was present in the exophytic area, in which some glands were
      cystically dilated. Part of the AEH had transformed into other histologic
      features with germ-cell-like differentiation, demonstrated by immunohistochemical
      positive reaction of placental alkaline phosphatase, alpha-fetoprotein, and human
      chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation,
      resulting in the development of well- and poorly differentiated adenocarcinoma
      and tumor exhibiting germ-cell-like differentiation. The patient died of a
      massive tumor extension 7 months after surgery. The AEH before MPA therapy and
      the recurrent tumors had genetically different characteristics based on evidence
      of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in
      the latter but not in the former, by analysis of genetic alterations using
      microsatellite markers.

PMID- 15144407
TI  - Ureteral leiomyoma causing hydronephrosis in Type 1 multiple endocrine neoplasia.
AB  - A rare case of leiomyoma of the ureter in a patient with type 1 multiple
      endocrine neoplasia (MEN) is reported. The case is of a Japanese man in his
      forties who had a past history of parathyroid gland hyperplasia, pancreatic islet
      cell tumors, and bilateral adrenocortical nodular hyperplasia. The leiomyoma,
      measuring 15 x 13 x 12 mm, was located in the right upper ureter, obstructing the
      lumen and causing hydronephrosis. Three small leiomyomas were also detected in
      the lower portion. Furthermore, histological examination revealed three tiny
      leiomyomatous nodules embedded in the muscular layer. It has been reported that
      type 1 MEN is often complicated by multiple leiomyoma in many organs, including
      the esophagus, stomach, lung, uterus, and skin. However, it is believed that this
      is the first report of leiomyomatosis of the ureter occurring in a patient with
      type 1 MEN. It should be recognized that multiple ureteral leiomyomas may develop
      in patients of type 1 MEN and can potentially result in hydronephrosis. The
      multiple development of leiomyoma suggests a causal relationship to MEN1 gene
      alteration.

PMID- 15144408
TI  - Myolipoma of the retroperitoneum.
AB  - A case of retroperitoneal myolipoma is reported. A 55-year-old woman with the
      main complaint of an abdominal mass was admitted to Teikyo University Hospital,
      Tokyo, Japan. Retroperitoneal liposarcoma was suspected based on magnetic
      resonance imaging, and the tumor was resected. The resected tumor was well
      encapsulated and 30 x 15 x 8 cm in size. Histologically, it consisted of mature
      adipose cells and smooth muscle cells. Neither nuclear atypia nor mitosis was
      observed in either component. The tumor was pathologically diagnosed as myolipoma
      of the retroperitoneum. Retroperitoneal myolipoma is often misdiagnosed
      radiologically as liposarcoma because the overwhelming majority of large
      retroperitoneal tumor containing fat is liposarcoma, however, the clinical course
      of myolipoma is quite different from that of liposarcoma. Although myolipoma is
      very rare, pathologists should consider it in the differential diagnosis of fat
      containing retroperitoneal masses.

PMID- 15144420
TI  - NBQX or topiramate treatment after perinatal hypoxia-induced seizures prevents
      later increases in seizure-induced neuronal injury.
AB  - PURPOSE: To evaluate the efficacy of NBQX (2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(f) quinoxaline-2,3-dione) and topiramate (TPM) given after hypoxia
      induced seizures in preventing the delayed effect of hypoxia on subsequent
      susceptibility to seizures and neuronal injury. METHODS: We used "two-hit" rodent
      seizure model to study the long-term effect of perinatal hypoxia on later kainate
      (KA) seizure-induced neuronal damage and investigated the therapeutic efficacy of
      a postseizure treatment protocol in reversing the conditioning effect of early
      life seizures. RESULTS: Hypoxia at P10 induces seizures without cell death but
      causes an increase in susceptibility to second seizures induced by KA as early as
      96 h after hypoxia, and this lowered seizure threshold persists to adulthood.
      Furthermore, perinatal hypoxia increases KA-induced neuronal injury at postnatal
      day (P)21 and 28/30. Repeated doses of NBQX (20 mg/kg) or TPM (30 mg/kg) given
      for 48 h after hypoxia-induced seizures prevent the increase in susceptibility to
      KA seizure-induced hippocampal neuronal injury at P28/30. CONCLUSIONS: Our
      results suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor blockade after hypoxia prevents the priming effect of perinatal hypoxia
      induced seizures and that this protection occurs independent of its
      anticonvulsant action.

PMID- 15144422
TI  - Severity of histopathologic abnormalities and in vivo epileptogenicity in the in
      utero radiation model of rats is dose dependent.
AB  - PURPOSE: Malformations of cortical development (MCDs) are a frequent cause of
      refractory epilepsy in humans. The in utero radiation model in rats shares many
      clinical and histopathologic characteristics with human MCDs. Previous studies
      reported the presence of clinical seizures in radiated rats, but also suggested a
      dose-dependent differential effect. METHODS: Time-pregnant Sprague-Dawley rats
      were irradiated on embryonic day E17 with 100 cGy (low dose), 145 cGy (medium
      dose), 175 cGy (high dose), or were left untreated. Their adult litters were
      implanted with bifrontal epidural and hippocampal depth electrodes and underwent
      long-term video-EEG monitoring. After 2 weeks of monitoring, the animals were
      killed and their brains processed for histological studies. RESULTS: Spikes were
      most frequently found in the rats that were subjected to low- and medium-dose
      radiation at E17 and were less frequently seen in the animals that were subjected
      to high-dose radiation. No interictal spikes were found in any of the control
      animals. Seizures were recorded in three of five animals of the medium-dose
      group. Histological studies showed a dose-dependent decrease in cortical
      thickness as well as an increase of cortical and hippocampal disorganization.
      CONCLUSIONS: In vivo epileptogenicity in radiated animals was present only in
      mild or moderate MCD. No in vivo epileptogenicity was seen in severe radiation
      induced MCD.

PMID- 15144423
TI  - Freeze lesion-induced focal cortical dysplasia predisposes to atypical
      hyperthermic seizures in the immature rat.
AB  - PURPOSE: To determine the effects of focal cortical dysplasia on the behavioral
      and electrographic features of hyperthermia-induced seizures (HSs) in rats.
      METHODS: A right sensorimotor cortex freeze lesion was induced in postnatal day 1
      (P1) rat pups, and HSs were provoked at P10 under continuous monitoring of core
      temperature; EEGs were recorded from the right amygdala during and after
      hyperthermia. Controls included both sham-operated at P1 and naive rats. RESULTS:
      HSs began with jaw myoclonus, followed by hindlimb clonus and generalized
      convulsions (GCs), and terminated by a period of posthyperthermia depression. The
      threshold temperature and latency of jaw myoclonus were similar across the
      groups. However, both the threshold temperature and latency of GCs were
      significantly lower in lesioned pups than in controls (40.5 +/- 0.5 degrees C, n
      = 24, vs. 42.0 +/- 0.2 degrees C, n = 21; p < 0.001; 6.7 +/- 0.6 min, n = 20, vs.
      8.4 +/- 0.6 min, n = 22; p < 0.05). In lesioned pups, the threshold and latencies
      for jaw myoclonus and hindlimb clonus were similar, whereas in controls, the
      progression from one to the other was marked by significant differences in both
      parameters. Posthyperthermia depression was longer in lesioned (13.3 +/- 1.2 min,
      n = 21) than in control (8.0 +/- 0.8 min, n = 20; p < 0.0001) pups. Ictal EEG
      activity was recorded during both behavioral seizures and posthyperthermia
      depression. CONCLUSIONS: An HS in rats with a localized freeze lesion results in
      lower threshold GC and prolonged ictal manifestations, thus supporting a
      pathophysiologic link between focal cortical dysplasia and atypical febrile
      seizures, conditions that have a high prevalence in children with mesial temporal
      lobe epilepsy.

PMID- 15144421
TI  - FMRI of brain activation in a genetic rat model of absence seizures.
AB  - PURPOSE: EEG-triggered functional magnetic resonance imaging (fMRI) was used to
      identify areas of brain activation during spontaneous spike-and-wave discharges
      (SWDs) in an epileptic rat strain under awake conditions. METHODS: Spontaneous
      absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo
      planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level-dependent (BOLD)
      signal was triggered based on EEG recordings during imaging. Images obtained
      during spontaneous SWDs were compared with baseline images. RESULTS: Significant
      positive BOLD signal changes were apparent in several areas of the cortex and
      several important nuclei of the thalamus. In addition, no negative BOLD signal
      was found in any brain area. CONCLUSIONS: We have shown that EEG-triggered BOLD
      fMRI can be used to detect cortical and thalamic activation related to the
      spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These
      results draw an anatomic correlation between areas in which increased BOLD signal
      is found and those in which SWDs have been recorded. In addition, no negative
      BOLD signal was found to be associated with these spontaneous SWDs. We also
      demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic
      rat model of absence seizure.

PMID- 15144424
TI  - Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14
      families.
AB  - PURPOSE: Benign familial infantile convulsions (BFIC) is a form of idiopathic
      epilepsy. It is characterized by clusters of afebrile seizures occurring around
      the sixth month of life. The disease has a benign course with a normal
      development and rare seizures in adulthood. Previous linkage analyses defined
      three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31.
      However, a responsible gene has not been identified. We studied linkage in 16
      further BFIC families. METHODS: We collected 16 BFIC families, without an
      additional paroxysmal movement disorder, of German, Turkish, or Japanese origin
      with two to eight affected individuals. Standard two-point linkage analysis was
      performed. RESULTS: The clinical picture included a large variety of seizure
      semiologies ranging from paleness and cyanosis with altered consciousness to
      generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform
      discharges in six patients, and three ictal EEGs in three distinct patients
      revealed a focal seizure onset in different brain regions. In all analyzed
      families, we found no evidence for linkage to the BFIC loci on chromosomes 19q
      and 2q, as well as to the known loci for benign familial neonatal convulsions on
      chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be
      confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411,
      and the known region for BFIC could be narrowed to 22.5 Mbp between markers
      D16S690 and D16S3136. CONCLUSIONS: Our data confirm the importance of the
      chromosome 16 locus for BFIC and may narrow the relevant interval.

PMID- 15144425
TI  - Randomized, controlled clinical trial of zonisamide as adjunctive treatment for
      refractory partial seizures.
AB  - PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide
      (ZNS) as adjunctive treatment for patients with refractory partial seizures.
      METHODS: This randomized, double-blind, placebo-controlled study was conducted at
      four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and
      a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS
      treatment were given a 7-mg/kg/d dosage. When investigators found that adverse
      effects could be reduced by gradually introducing ZNS, patients were allowed to
      begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated
      over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary
      efficacy measures were the median percentage reduction from baseline in seizure
      frequency and the proportion of patients achieving a > or =50% reduction from
      baseline (responder rate). Patient and physician global assessments also served
      as indicators of efficacy. Safety was assessed primarily by treatment-emergent
      adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure
      frequency, which differed significantly from the 4.7% increase in placebo-treated
      patients. The responder rate for ZNS-treated patients was 26.9%, compared with
      16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients
      and 12.3% of placebo-treated patients considered their condition improved;
      similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo
      treated patients as improved. The most frequently reported adverse events with
      ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue.
      CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and
      significantly improved seizure control among patients with refractory partial
      seizures.

PMID- 15144426
TI  - Does hyperventilation elicit epileptic seizures?
AB  - PURPOSE: Voluntary hyperventilation has been advocated for many decades as an
      "activating" procedure to provoke clinical seizures and epileptiform discharges
      in subjects with suspected epilepsy who undergo standard EEG recordings. This
      study was undertaken to determine the effects of hyperventilation in patients
      with proven epilepsy. METHODS: We examined the records of 433 consecutive
      patients with proven epilepsy, as documented by long-term video-EEG studies. The
      patients underwent 5 min of voluntary hyperventilation during standard EEG
      recordings. All EEGs were interpreted by board-certified
      electroencephalographers. The patients ranged in age from 10 to 64 years; 384
      (88.7%) had localization-related and 48 (11.3%) generalized epilepsy syndromes.
      RESULTS: Hyperventilation was associated with a clinical seizure in two (0.46%)
      of the subjects (partial seizures in both cases). Interictal epileptiform
      discharges were interpreted as showing in increase in frequency during
      hyperventilation in 19 (4.4%) patients, when compared with the baseline EEG.
      CONCLUSIONS: Voluntary hyperventilation in patients with unequivocal epilepsy is
      rarely associated with either clinical seizures or an increase in frequency of
      epileptiform discharges.

PMID- 15144427
TI  - EEG and MEG source analysis of single and averaged interictal spikes reveals
      intrinsic epileptogenicity in focal cortical dysplasia.
AB  - PURPOSE: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings
      were used for noninvasive analysis of epileptogenicity in focal cortical
      dysplasia (FCD). The results of two different approach methods (multiple source
      analysis of averaged spikes and single dipole peak localization of single spikes)
      were compared with pre- and postoperative anatomic magnetic resonance imaging
      (MRI). PATIENTS: We studied nine children and adolescents (age, 3.5-15.9 years)
      with localization-related epilepsy and FCD diagnosis based on MRI. Five patients
      underwent epilepsy surgery, two of them after long-term recording with subdural
      grid electrodes, and one after intraoperative electrocorticography. METHODS: The
      122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for
      25 to 40 min. Interictal spikes were identified visually and used as templates to
      search for similar spatiotemporal spike patterns throughout the recording. With
      the BESA program, similar spikes (r > 0.85) were detected, averaged, high-pass
      filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal
      source analysis with a multishell spherical head model. Peak activity from single
      spikes was modeled by single dipoles for the same subset of spikes. Source
      localization was visualized by superposition on T1-weighted MRI and compared with
      the lesion identified in T1- and T2-weighted MRI. In the five cases undergoing
      epilepsy surgery, the results were correlated with invasive recordings,
      postoperative MRI, and outcome. RESULTS: In all cases, the analysis of averaged
      spikes showed a localization of onset- and peak-related sources within the
      visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284)
      were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91%
      localized within the lesion with MEG, and 93.5% with EEG. In three of five
      patients operated on, the resected area included the onset zones of averaged EEG
      and MEG spike activity. These patients had excellent postoperative outcome,
      whereas the others did not become seizure free. CONCLUSIONS: Consistent MEG and
      EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic
      epileptogenicity in FCD.

PMID- 15144429
TI  - Parietal lobe epilepsy: the semiology, yield of diagnostic workup, and surgical
      outcome.
AB  - PURPOSE: To characterize the clinical features, the prognostic value, and
      diagnostic sensitivities of various presurgical evaluations and the surgical
      outcomes in parietal lobe epilepsy (PLE), we describe 40 patients who were
      diagnosed as having PLE, including 27 surgically treated patients. METHODS: The
      diagnosis was established by means of a standard presurgical evaluation,
      including magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission
      tomography (FDG-PET), ictal single-photon emission tomography (SPECT), and scalp
      video-electroencephalography (EEG) monitoring, with additional intracranial EEG
      monitoring in selected cases. RESULTS: Among the 40 patients, 27 experienced at
      least one type of aura. The most common auras were somatosensory (13 patients),
      followed by affective, vertiginous, and visual auras. The patients had diverse
      manifestations. Eighteen patients showed simple motor seizure, followed by
      automotor seizure, and dialeptic seizure. Two patients manifested generalized
      tonic-clonic seizures only, and 19 patients experienced more than one type of
      seizure. The surgical outcome was favorable in 22 of 26 patients including 14 who
      were seizure free. Patients with localized MRI abnormality had a higher
      probability to be seizure free, with marginal significance (p = 0.062), whereas
      other diagnostic modalities failed to predict the surgical outcome. In the
      seizure-free group, localization sensitivity was 64.3% by MRI, 50% by PET, 45.5%
      by ictal SPECT, and 35.7% by ictal EEG. The concordance rate of the various
      diagnostic modalities was higher in the seizure-free group than in the non
      seizure-free group, although it did not reach statistical significance.
      CONCLUSIONS: Seizures, in the case of PLE, can manifest themselves in a wider
      variety of ways than was previously thought. Surgical outcome was favorable in
      most of the patients. MRI abnormality and concordance of different diagnostic
      modalities were associated with high seizure-free rate.

PMID- 15144428
TI  - Correlation between 1H MRS and memory before and after surgery in mesial temporal
      lobe epilepsy with hippocampal sclerosis.
AB  - PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate
      neuronal loss and gliosis, may be used as a sensitive tool for lateralization of
      temporal lobe epilepsy (TLE). Although the correlation between the memory
      functions and 1H MRS has been investigated, its predictive value after surgery
      has not been studied previously. This study evaluated memory and 1H MRS values of
      medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE
      HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two
      patients underwent memory tests and 1H MRS investigation before and 6 months
      after SAH and were compared with nine control subjects. RESULTS: The 1H MRS
      scores were found to be significantly low on the pathological side of the
      patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of
      left TLE patients were correlated only with verbal memory scores. Statistical
      analysis did not reveal any significance for nonverbal memory scores for both TLE
      groups on either side, which showed no significant correlation between material
      specificity and 1H MRS findings. Conversely, regression analyses demonstrated
      that high right- and low left-sided 1H MRS values obtained before surgery may
      predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS
      can be considered as a useful tool to determine the lateralization in patients
      with MTLE-HS before the surgery. Although only a weak relation exists between the
      MRS values and memory scores, presurgical MRS scores may be predictive for a
      possible deterioration in verbal memory after surgery. However, further studies
      with higher numbers of cases are needed for confirmation of the results.

PMID- 15144430
TI  - Cognitive, psychosocial, and family function one year after pediatric epilepsy
      surgery.
AB  - PURPOSE: Assumptions regarding the benefits of seizure control after pediatric
      epilepsy surgery for cognitive, psychosocial, and family function were explored
      in a prospective study of 51 children with intractable epilepsy. METHODS: Thirty
      children who underwent surgery were studied before and 1 year after surgery, and
      a comparison group of 21 children with medically refractory seizures was examined
      at comparable times. RESULTS: One year after surgery, 57% of the surgical group
      was seizure free. Seizure status after surgery did not predict change over time
      in any of the areas measured. Cognitive and psychosocial status did not change
      over time in either group, and the strongest predictor of individual change in
      psychosocial status in the surgical group was baseline level of function. Within
      the surgical group, a trend toward an increase in independence promotion was
      noted in the family, but the children's satisfaction with the family declined.
      CONCLUSIONS: These findings challenge the assumption that elimination of seizures
      will result in improved cognitive, psychosocial, and family functioning, at least
      within the first year after surgery.

PMID- 15144431
TI  - Development of syndrome severity scores for pediatric epilepsy.
AB  - PURPOSE: A severity rating for each of the pediatric epilepsy syndromes can
      contribute to a more comprehensive understanding of seizure condition severity.
      We describe the development of the Epilepsy Syndrome Severity Scores-Child (ESSS
      C). METHODS: The Delphi Technique was used to establish severity scores for
      pediatric epileptic syndromes as defined by the International League Against
      Epilepsy (ILAE). Pediatric neurologists with expertise in epilepsy were asked to
      rate the severity of each syndrome on a scale of 1 to 10, considering: (a)
      response to medical treatment, (b) seizure severity, and (c) long-term prognosis.
      Syndrome severity ratings took place in four different rounds. Experts provided
      initial scores in rounds 1 and 2. RESULTS: Of the 18 experts who agreed to
      participate in the development of the scale, 12 completed all four rounds. The
      median served as the syndrome severity score if the mean and median agreed within
      0.5. Otherwise, whichever of these two numbers was closest to the mode was
      selected. Syndromes that were rated with high severity scores (9 or 10) or low
      severity scores (1 or 2) had unanimous or near unanimous ratings. The syndromes
      with scores in the middle range (4 to 8) had a wider range of ratings.
      CONCLUSIONS: If further studies provide empirical support for the validity of
      these epileptic syndrome severity scores, then the ESSS-C has potential for use
      both clinically and in future research in the prediction of outcomes of
      treatments.

PMID- 15144432
TI  - Accidents in patients with epilepsy: types, circumstances, and complications: a
      European cohort study.
AB  - PURPOSE: To investigate the risk of accidents in a cohort of patients with
      epilepsy and in matched nonepilepsy controls, by type, circumstances, and
      complications. METHODS: A total of 951 children and adults with idiopathic,
      cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in
      secondary and tertiary centers in eight European countries (England, Estonia,
      Germany, Italy, the Netherlands, Portugal, Russia, and Slovenia) were followed up
      prospectively for 17,484 and 17,206 person-months and asked to report any
      accident requiring medical attention, its site, and complications. Risk
      assessment was done by using actuarial methods, relative risks (RRs), and 95%
      confidence intervals (CIs). RESULTS: During the study period, 199 (21%) patients
      and 123 (14%) controls reported an accident (p < 0.0001); 24% were seizure
      related. The cumulative probability of accidents at 12 and 24 months was 17 and
      27% in the cases and 12 and 17% in the controls. The risk was highest for
      concussions (RR, 2.6; 95% CI, 1.2-5.8), abrasions (RR, 2.1; 95% CI, 1.1-4.0), and
      wounds (RR, 1.9; CI, 1.2-3.1). Domestic accidents prevailed in both groups,
      followed by street and work accidents, and were more common among cases. Compared
      with controls, patients with epilepsy reported more hospitalization,
      complications, and medical action. Disease characteristics associated with an
      increased risk of accidents included generalized epilepsy (concussions), active
      epilepsy, and at least monthly seizures (abrasions). Most risks decreased,
      becoming nonsignificant after excluding seizure-related events. CONCLUSIONS:
      Patients with epilepsy are at higher risk of accidents and their complications.
      However, the risk was substantially lower after exclusion of seizure-related
      events.

PMID- 15144433
TI  - Economic evaluation of epilepsy in Kiremba (Burundi): a case-control study.
AB  - PURPOSE: Epilepsy is a common disease whose prevalence across Africa is extremely
      variable (from 5 to 74 per thousand ). Its social and economic consequences in
      this continent are not well established. The objective of this study was to
      compare the cost of care of patients with epilepsy with that of controls in the
      commune of Kiremba in Burundi. METHODS: The survey was carried out in the commune
      of Kiremba from March 1, 2001, to April 30, 2001. A sample of cases (patients
      with epilepsy) and controls was taken from the general population. The economic
      analysis was conducted from the viewpoint of the patient. Data collected were
      direct medical costs (consultations, admissions to hospital, complementary
      examinations, treatments) and indirect costs (evaluated from the number of days
      of family life disrupted). RESULTS: In this study, 1,056 patients were included
      (352 patients with epilepsy and 704 controls). The total annual cost of patients
      with epilepsy was US dollars 11.0 against US dollars 7.3 for controls (p = 0.03).
      The indirect costs represented 75.8% of the total cost. For the people with
      epilepsy that took antiepileptic treatment (n = 18), the annual average total
      cost became US dollars 48.4. The number of disrupted days was 10.2 days (SD, 18.7
      days) for the treated patients with epilepsy and 2.0 days (SD, 9.0 days) for the
      untreated ones (p < 0.001). CONCLUSIONS: Epilepsy was responsible for an extra
      cost: an increased direct cost along with more disruption of family life. This
      extra cost remained after adjustment for use of health care and antiepileptic
      treatments. Various measures could be envisioned to reduce the impact of indirect
      costs.

PMID- 15144434
TI  - Antimyoclonic effect of levetiracetam in 13 patients with Unverricht-Lundborg
      disease: clinical observations.
AB  - PURPOSE: Disabling myoclonus is the main symptom in long-standing Unverricht
      Lundborg disease (ULD), and levetiracetam (LEV) appears to be an effective
      anticonvulsant with promising short-term antimyoclonic properties. METHODS: LEV
      was prescribed to 13 patients with ULD. We retrospectively analyzed the efficacy
      of LEV on seizure frequency and on myoclonus, by using a simplified myoclonus
      rating score, and compared the patients' status before LEV and at the last follow
      up. They were two women and 11 men, aged 14 to 52 years (mean, 36.5 years), with
      a disease duration of 4 to 40 years (mean, 24.3 years). LEV was given at 2,000 to
      4,000 mg/d for 0.5 to 26 months (mean, 13.8 months). RESULTS: One patient stopped
      LEV within 2 weeks because of side effects and lack of efficacy. None of the
      other 12 patients reported side effects. The average myoclonus score
      significantly changed from 3.1 to 2.4 (p = 0.01), but only eight had a measurable
      improvement. CONCLUSIONS: The best effects were noted in the younger patients. In
      patients previously treated with high-dose piracetam (PIR), discontinuation of
      PIR was not always well tolerated, and a combination of PIR at lower doses and
      LEV appeared to be a practical solution. LEV should probably be considered as a
      major treatment option early in the course of ULD.

PMID- 15144435
TI  - The coexistence of idiopathic generalized epilepsy and partial epilepsy.
AB  - PURPOSE: To describe the clinical, EEG, and imaging data of a series of patients
      with features of both idiopathic generalized epilepsy (IGE) and partial epilepsy.
      METHODS: A computerized database of all patients attending the regional epilepsy
      clinic was used to identify all patients with IGE. Case notes were reviewed, and
      cases with clinical evidence of co-existing partial epilepsy identified. RESULTS:
      Nine cases with clinical features of a partial and generalized-onset epilepsy and
      with electrophysiological evidence of IGE are presented. This represented <1% of
      the overall IGE population in the clinic. Five (55.6%) patients are currently in
      remission, with successful epilepsy surgery in one patient. CONCLUSIONS: The
      coexistence of IGE and partial epilepsy is uncommon, and if appropriate treatment
      with a broad-spectrum antiepileptic drug is given, then the prognosis can be
      good. Surgery should be considered for those cases with medically intractable
      partial-onset seizures as part of this syndrome.

PMID- 15144438
TI  - ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis.
AB  - Experts discussed the definition, natural history, pathologic features,
      pathogenesis, electroclinical, neurophysiological, neuropsychological, structural
      and functional imaging findings, as well as surgical outcome in mesial temporal
      lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting
      consensus process the ILAE Commission Neurosurgery of epilepsy accepted the
      resulting conclusions as state-of-the art report on MTLE-HS. The majority of
      contributors considered MTLE-HS to represent a sufficient cluster of signs and
      symptoms to make up a syndromic diagnostic entity.

PMID- 15144437
TI  - Does glucocorticoid administration prevent late seizures after head injury?
AB  - PURPOSE: Preventing posttraumatic epilepsy has been a difficult challenge. In
      this study we evaluated the association between glucocorticoid administration
      after traumatic brain injury (TBI) and posttraumatic seizures. METHODS: We
      examined a seizure-prevention trial database of 404 patients with severe TBI for
      exposure to glucocorticoids in the early (<1 week) posttraumatic period. After
      controlling for seizure risk, we compared the odds of developing first and second
      late posttraumatic seizures between those that received glucocorticoids and those
      that did not. RESULTS: Patients dosed with glucocorticoids within 1 day of their
      TBI were more likely to develop first late seizures than were those without [p =
      0.04; hazard ratio = 1.74; 95% confidence interval (CI), 1.01-2.98]; whereas
      those receiving glucocorticoids > or =2 days after their injury had no similar
      association (p = 0.66; hazard ratio = 0.77; 95% CI, 0.23-2.56; p = 0.10 among the
      three groups). Receiving glucocorticoids within 1 day, or > or =2 days after TBI
      was not associated with second late seizure development. CONCLUSIONS:
      Glucocorticoid treatment after TBI is not associated with decreased late
      posttraumatic seizures, and early treatment is associated with increased seizure
      activity.

PMID- 15144436
TI  - Regional cerebral hyperperfusion with ictal dystonic posturing: ictal-interictal
      SPECT subtraction.
AB  - PURPOSE: Ictal-interictal single-photon emission computed tomography (SPECT)
      subtraction was performed to find brain structures related to ictal dystonic
      posturing (DP) in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-two
      patients with mesial TLE who had ictal and interictal SPECTs were included. They
      were divided into two groups; DP group with ictal dystonia during ictal SPECT (n
      = 15) and Non-DP group without ictal DP (n = 17). Ictal-interictal SPECT
      subtraction was performed, and then subtracted SPECT was coregistered with brain
      spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI). The ictal
      hyperperfusion on subtracted SPECT was analyzed in basal ganglia, frontal cortex,
      thalamus, temporal lobe, and insular cortex. RESULTS: The incidences of ictal
      hyperperfusion on brain regions in DP versus Non-DP groups were 80.0% (12 of 15
      patients) versus none (0 of 17), p = 0.001, chi2, in caudate nucleus; 93.3% (14
      of 15) versus 47.0% (eight of 17), p = 0.005, in putamen; and 80.0% (12 of 15)
      versus 41.2% (seven of 17), p = 0.026, in thalamus. No significant difference of
      ictal hyperperfusion was found in globus pallidus, temporal lobes, insular and
      frontal cortices between DP and Non-DP groups. DP patients showed an earlier age
      at seizure onset [8.6 years (DP) vs. 15.7 years (Non-DP) (p = 0.015)] and a
      longer duration of seizure history [19.0 years (DP) vs. 11.9 years (Non-DP) (p =
      0.015)]. CONCLUSIONS: Caudate nucleus, putamen, and thalamus were significantly
      related to the ictal DP during TLE seizures. Our study showed first an active
      involvement of the caudate nucleus in the generation of ictal DP.

PMID- 15144439
TI  - Late language transfer vs. immutability of command center.

PMID- 15144442
TI  - Socio-economic burden of permanent incisor replantation on children and parents.
AB  - This study describes the socio-economic burden and attitudes of children and
      their parents following replantation of avulsed incisors. Records of 80 patients
      with 99 avulsion injuries treated in a teaching hospital clinic from 1988 to 1999
      were reviewed. Mean age at time of injury was 10.6 years (range = 6.6-17.7
      years). Complete records for a minimum of 1 year were obtained for 43 patients
      with 60 replanted incisors. Mean treatment procedures provided during the first
      year included 5.5 diagnostic periapical radiographs, 1.9 occlusal radiographs,
      1.3 pulpectomies, and 2.7 pulp medicament applications. The mean estimated
      treatment cost and direct time (dentist) for first-year post-trauma management
      was 1465 dollars CAD and 7.2 h, respectively. Treatment costs were significantly
      higher during the first year post-trauma for patients who had their incisors
      extracted (P = 0.04), but there was no significant difference in direct treatment
      time between the two groups (P = 0.19). Twenty-one patient-parent pairs were
      surveyed for a number of qualitative factors. Ninety per cent of patients and 86%
      of parents reported that school and work time was lost. Even after having gone
      through the painful experience of replantation, the demands of recall, and in
      some cases, extraction, the majority of patients (67%) and parents (81%) stated
      that they would have still made the same (replantation) decision. Patient and
      parent responses were not statistically different (P = 0.453). Almost half the
      parents stated they would be willing to pay over 2000 dollars CAD to save an
      incisor. Patients rated retention of an incisor as significantly more important
      than infraocclusion. This is the first study to quantify the treatment burden of
      replantation of avulsion injuries exclusively in the pediatric population. This
      study describes the socio-economic burden and responsibilities of patient/parent
      and dentist and their role in informed consent.

PMID- 15144443
TI  - Dental injury among Brazilian schoolchildren in the state of Sao Paulo.
AB  - To describe the distribution of dental trauma in Brazilian schoolchildren and its
      association with demographic, environmental and clinical factors. A random sample
      of 73 243 schoolchildren's oral examination records from private and public
      units, selected from 131 cities within the state of Sao Paulo, Brazil, was
      analysed. Trauma was assessed based on international methodological standards
      prescribed by the World Health Organization for Oral Health Surveys (1997).
      Proportions obtained were compared between urban and rural schools, as well as
      between private and public units. Oral health status indices were estimated based
      on the decayed, missing and filled teeth (DMFT) index - the average number of
      decayed, missing and filled teeth; the proportion of caries-free 5-year-old
      schoolchildren and anterior maxillary overjet among 12-year-old schoolchildren.
      The prevalence of dental trauma in anterior dentition was of 2.4, enrolling
      average 1.2 teeth per child. A rate of 2.4 impaired anterior teeth per thousand
      was obtained, upper central incisors being those that were most affected - 7.7 in
      every 10. Among 8- to 11-year-old children, the rates grew regularly. The
      proportion of dental trauma was significantly higher in boys than in girls (P <
      0.01), and gender prevalence ratio was of 1.58 for boys. The results showed
      positive associations between dental trauma and caries-free 5-year-old
      schoolchildren (P = 0.003), anterior maxillary overjet > or =3 mm (P < 0.001),
      and private school as a socio-economic proxy indicator (P = 0.048).

PMID- 15144444
TI  - Influence of the type of dental trauma on the pulp vitality and the time elapsed
      until treatment: a study in patients aged 0-3 years.
AB  - The purpose of the present study was to determine the influence of the type of
      trauma on the pulp vitality and the time elapsed until seeking dental care in
      children aged 0-3 years seen at the Baby Clinic of the Aracatuba Dental School,
      UNESP. A total of 1813 records were analyzed. Two hundred and three patients,
      corresponding to 302 traumatized teeth, were assessed clinically and
      radiographically. Hard-tissue injuries were the most frequent (52%), with a
      predominance of enamel crown fractures (41.4%), followed by concussions (12.6%)
      and intrusions (11.6%). Clinical and radiographic examination revealed that 72%
      of the traumatized teeth maintained pulp vitality. In the case of supporting
      tissue lesions, 51.1% of the patients sought care within 1-15 days after injury,
      while in the case of hard-tissue injuries, 52.7% sought care only after 16 days.
      The results showed that supporting-tissue injuries had a significant influence on
      the faster seeking of dental care.

PMID- 15144445
TI  - Incidence of cerebral concussions associated with type of mouthguard used in
      college football.
AB  - Controversy exists among sports dentists as to whether or not a 'custom made'
      mouthguard is more effective in reducing the incidence of cerebral concussion
      than the boil-and-bite 'non-custom made' mouthguard. While members on each side
      remain steadfast in their opinion, not a single epidemiological study has been
      conducted to investigate the effect of type of mouthguard worn on the incidence
      of cerebral concussion. The aim of this study was to determine if there was a
      difference between the type of mouthguard worn and the incidence of cerebral
      concussions among National Collegiate Athletic Association (NCAA) Division I-A
      football players. During the 15-week 2001 college football season, trainers
      entered, via an interactive web site, weekly data for each game and practice
      sessions for the preceding week. Eighty-seven (76%) out of a possible 114
      Division I teams participated. A total of 506 297 athletic exposures were
      recorded; 369 brain concussions were reported. The incidence of cerebral
      concussions per 1000 exposures was 0.73. Utilizing a risk ratio with a 95%
      confidence interval, no statistical difference occurred in the incidence of
      cerebral concussions between football players wearing custom made versus non
      custom made mouthguards (0.990,1.750). In this study, there was no advantage of
      wearing a custom made mouthguard over a boil-and-bite mouthguard to reduce the
      risk of cerebral concussion in football players.

PMID- 15144446
TI  - Are all mouthguards the same and safe to use? The influence of occlusal
      supporting mouthguards in decreasing bone distortion and fractures.
AB  - The safety benefits of mouthguards have been demonstrated in many studies, with
      many authors and sports dentists strongly recommending the wearing of
      mouthguards. However, wearing a mouthguard with incorrect occlusion might cause a
      variety of problems. It comes as no surprise that a traumatic blow to the chin,
      while wearing an insufficient mouthguard lacking anterior contact, can result in
      severe distortions to the mandibular bone, and bone fractures. The aim of this
      study was to clarify how ineffective insufficient occlusal supporting mouthguards
      are and how dangerous they can be to use. Consequently, in this study, occlusal
      supportive areas were varied and accelerations of head and distortions of the
      mandible were measured using an artificial skull model and a pendulum impact
      device. As a result, the distortions of the mandible tended to increase as the
      supported area decreased. On the contrary, accelerations of the head decreased as
      the occlusion part decreased. Thus, a lot of impact energy was consumed in the
      distortion of the mandible; accordingly, it seemed that only a little destructive
      energy was transferred to the head. From this study, it would seem that wearing a
      mouthguard, which is insufficient in the occlusion, has the potential of causing
      a bone fracture of the mandible. Consequently, mouthguards should have proper
      occlusion.

PMID- 15144447
TI  - Fracture resistance of re-attached coronal fragments--influence of different
      adhesive materials and bevel preparation.
AB  - The purpose of this study was to investigate the fracture resistance of re
      attached coronal fragments of teeth using different materials and tooth
      preparations. Seventy-two recently extracted bovine incisors were selected. Eight
      incisors were maintained without any preparation as a control group. The incisal
      third of the other teeth was sectioned using a diamond saw. In one group (n =
      32), a 2-mm bevel was prepared, whereas in the second group no preparation was
      made (n = 32). The specimens (beveled and non-beveled) were divided in four
      groups (n = 8) and re-attached with the following materials: a dual-cured resin
      cement RelyX ARC (RX); a chemically cured composite Bisfil 2B (B2); a light-cured
      composite Z250 (Z2); and a one-bottle adhesive Single Bond (SB). The bevel region
      was restored with adhesive and composite. All materials were used according to
      manufacturer's directions. A light-curing unit was used to polymerize the
      materials. Specimens were stored in saline solution for 72 h. De-bonding
      procedures were performed in a testing machine with cross-head speed of 0.6 mm
      min(-1). The load was applied in the incisal third. The resistance to fracture
      for control group was 70 (7) kg. The fracture resistance for non-beveled and
      beveled specimens were: SB, 3.3 (2.4) and 17.0 (4.1); RX, 11.5 (3.0) and 16.3
      (3.1); Z2, 14.4 (4.2) and 20.5 (1.7); and B2, 19.5 (3.5) and 32.5 (7.4) kg.
      Analysis of variance (anova) and Fisher's protected least significant difference
      (PLSD) test disclosed significant influence for materials and cavity designs (P =
      0.001). The highest failure loads were obtained with the B2 group and then with
      the Z2 with either bevel or non-bevel. RX produced lower failure loads than the
      restorative composites. The lowest failure load was obtained with SB in the non
      beveled group. No technique studied was able to attain the fracture resistance of
      the control group and both materials and tooth preparation influenced the
      fracture resistance.

PMID- 15144448
TI  - In vitro assessment of dentinal permeability after the use of ultrasonic
      activated irrigants in the pulp chamber before internal dental bleaching.
AB  - This in vitro study aimed to assess dentin permeability quantitatively after the
      use of different irrigants into the pulp chamber, with or without ultrasonic
      activation, before the application of an internal bleaching agent. Thirty
      maxillary anterior teeth, treated endodontically, were randomly assigned to six
      groups, according to the irrigant used: group I, distilled water; group II, 17%
      EDTA; group III, 1% sodium hypochlorite; for groups IV, V, and VI, respectively,
      the same solutions were used, but were ultrasonicated. In groups I, II, and III,
      the irrigant that filled the pulp chamber was left undisturbed for 15 s and was
      then aspirated; in groups IV, V, and IV, the irrigants were placed into the pulp
      chamber, ultrasonic-activated for 15 s, and were then aspirated. This sequence
      was repeated three times for all groups. Afterwards, for all groups, the pulp
      chamber was dried, filled with a bleaching agent, and sealed with glass ionomer
      cement. At each change of the whitening agent, these procedures were repeated.
      Then, the temporary restorations were removed, access cavities were cleaned, and
      teeth were immersed in a 10% copper sulfate aqueous solution, submitted to vacuum
      and immersed in a 1% rubianic acid alcohol solution. Copper ion penetration was
      revealed by the rubianic acid. After staining, roots were removed at the cemento
      enamel junction (CEJ) and sectioned in a mesiodistal direction starting from the
      cervical plug level. The sections were thinned, observed under an optical
      microscope, the images were digitized, and copper ion penetration was measured in
      each section using a specific software. Means and SD were: group I, 2.41 (+/
      1.45); group II, 5.22 (+/-1.79); group III, 8.32 (+/-2.55); group IV, 3.73 (+/
      0.89); group V, 14.83 (+/-4.99); and group VI, 10.51 (+/-2.65). Statistical
      analysis using two-way anova and Tukey test showed that, regardless of the
      irrigant, ultrasonication increased dentinal permeability (P < 0.01). Comparing
      the overall effectiveness of the tested solutions, EDTA yielded the greatest
      increase in dentinal permeability (P < 0.01). Based on these results, it may be
      concluded that use of ultrasonic-activated irrigants in the pulp chamber, before
      the accomplishment of internal dental bleaching procedures, may result in a
      remarkable increase of dentin permeability, which may enhance the efficiency of
      the whitening agent.

PMID- 15144449
TI  - Trauma to anterior implants.
AB  - The replacement of anterior teeth with an implant-supported restoration is
      recognized as an efficient and successful treatment. One of the rare
      complications that can occur with dental implants is the fracture of either the
      implant or the superstructure because of biomechanical overload or occlusal
      force. In contrast to the permanent dentition, there is limited information about
      how osseointegrated implants or the periimplantary bone behave after dental
      trauma. This article presents a case of trauma to anterior implants and
      illustrates the effects to the titanium screw and the surrounding tissue.

PMID- 15144450
TI  - Combined technique with polyethylene fibers and composite resins in restoration
      of traumatized anterior teeth.
AB  - Traumatized anterior teeth need quick esthetic and functional repair. Esthetic
      requirements of anterior teeth require the use of composite materials which, in
      the most complex cases, can be used in association with fibers so as to improve
      their mechanical resistance. Many kinds of fibers are available. The authors
      considered parameters such as physical properties, water absorption, ease of
      cutting and of laying. Polyethylene fibers appear to have the best properties in
      elasticity, translucency, adaptability, tenaciousness, resistance to traction and
      to impact. Fifteen children, between 7 and 13 years old, with crown fractures of
      the anterior sector were treated. In the case of a simple crown fracture, the
      missing part was restored by polyethylene fibers and composite resins. In the
      case of a complex crown fracture needing endodontic treatment, the fibers were
      used as a central core stump in order to restore the dental morphology. At
      control examinations, the teeth restored by this technique were acceptable, both
      in function and in aesthetics. Thus, the authors recommend this combined
      technique for predictable restoration of traumatized anterior teeth.

PMID- 15144451
TI  - Accidental lodgment of an air gun pellet in the maxillary sinus of a 6-year old
      girl: a case report.
AB  - Air gun, although considered a toy, can cause injuries ranging from trivial to
      very grievous. The type and severity of injuries depend on the type of air gun
      used, the distance at which it is fired, and the anatomic site at which the
      pellet hits. An interesting case involving a young girl, who was accidentally hit
      by an air gun pellet at a village fair, is described. The pellet penetrated the
      maxillary bone to be lodged in the sinus. The treatment strategy along with
      literature review on short- and long-term complications of air gun injuries is
      presented.

PMID- 15144452
TI  - Pulp canal obliteration in an unerupted permanent incisor following trauma to its
      primary predecessor: a case report.
AB  - Trauma to a primary tooth may result in damage to the underlying developing
      permanent tooth bud because of the close proximity between the root of the
      primary tooth and its permanent successor. We report an unusual case where injury
      to the primary dentition resulted in pulp canal obliteration (PCO) of a permanent
      maxillary central incisor prior to its eruption. The other permanent maxillary
      central incisor was diagnosed as malformed because of trauma to the primary
      dentition at an earlier age. The occurrences of PCO or crown malformation dose
      not routinely disrupt the eruption of those teeth. Periodic assessment is
      required to determine the need for endodontic intervention.

PMID- 15144454
TI  - How allergenic is food?

PMID- 15144453
TI  - Bifid mandibular condyle: a case report.
AB  - A case of left bifid mandibular condyle (BMC) is reported in a 36-year-old
      female. The patient had a history of trauma in childhood. From the radiological
      examination, the left condyle was seen to have two anterioposteriorly situated
      heads. BMC is an extremely rare condition, where the condyle is duplicated or
      lobulated. The literature on BMC is reviewed, and possible cause of trauma and
      consequences of the anomaly are discussed.

PMID- 15144455
TI  - Eosinophil trafficking: new answers to old questions.

PMID- 15144456
TI  - Epidemiological aspects of paediatric asthma.

PMID- 15144457
TI  - Asthma in India: applying science to reality.

PMID- 15144458
TI  - A consensus protocol for the determination of the threshold doses for allergenic
      foods: how much is too much?
AB  - BACKGROUND: While the ingestion of small amounts of an offending food can elicit
      adverse reactions in individuals with IgE-mediated food allergies, little
      information is known regarding these threshold doses for specific allergenic
      foods. While low-dose challenge trials have been conducted on an appreciable
      number of allergic individuals, a variety of different clinical protocols were
      used making the estimation of the threshold dose very difficult. OBJECTIVE: A
      roundtable conference was convened to develop a consensus clinical protocol for
      low-dose challenge trials for the estimation of threshold doses for specific
      allergenic foods. METHODS: In May 2002, 20 clinical allergists and other
      interested parties were invited to participate in a roundtable conference to
      develop consensus of the key elements of a clinical protocol for low-dose
      challenge trials. RESULTS: A consensus protocol was developed. Patients with
      convincing histories of food allergies and supporting diagnostic evidence
      including past challenge trials or high CAP-RAST scores can be enrolled in low
      dose challenge trials. Care must be taken with younger patients to assure that
      they have not outgrown their food allergy. An approach was developed for the
      medication status of patients entering such trials. Challenge materials must be
      standardized, for example, partially defatted peanut flour composed of equal
      amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish).
      Challenge materials must be appropriately blinded with sensory evaluation used to
      confirm the adequacy of blinding. A double-blind, placebo-controlled design
      should be used for low-dose challenge trials. Low-dose challenge trials would
      begin at doses of 10 microg of the allergenic food and would continue with doses
      of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending
      upon the expert judgement of the physician; even higher doses might be applied to
      assure that the patient is indeed reactive to the particular food. A 30-min time
      interval would be used between doses, and reactive doses would be expressed as
      both discrete and cumulative doses. The goal of each challenge would be to
      develop objective symptoms; trials should not be discontinued on the basis of
      subjective symptoms only. Statistically, a minimum of 29 patients would be
      enrolled in low-dose challenge trials for each allergenic food because 0 reactors
      out of 29 patients at a particular dose allow the conclusion that there is 95%
      certainty that 90% of allergic individuals will not react to that dose.
      CONCLUSION: A consensus protocol was developed. Using this protocol, it will be
      possible to estimate threshold doses for allergenic foods, the lowest amount that
      elicits mild, objective symptoms in highly sensitive individuals.

PMID- 15144459
TI  - Syndecan-4-dependent migration of human eosinophils.
AB  - BACKGROUND: Heparan sulphate proteoglycans (HSPGs) are important participants in
      cell surface signalling and critical in controlling cell behaviour. They modulate
      inflammatory cell maturation and activation, leucocyte rolling, adhesion to
      endothelium as well as extravasation and chemotaxis. Whether eosinophil's
      function is affected has not yet been reported. OBJECTIVE: We investigated the
      effects of transgenic, recombinant anti-thrombin III and Kybernin P, an anti
      thrombin III concentrate, as HSPG ligands on spontaneous and chemokine-triggered
      migration of normal eosinophils from human peripheral blood in modified Boyden
      chamber micropore filter assays. METHODS: Eosinophils from human peripheral blood
      were purified using magnetic antibody cell sorting. The signalling mechanisms
      required for anti-thrombin-dependent migration were studied using signalling
      enzyme blockers. Expression of HSPG core protein mRNA was studied by PCR.
      RESULTS: Pre-treatment of eosinophils with anti-thrombin III inhibited chemotaxis
      toward optimal concentrations of eotaxin or RANTES (regulated upon activation
      normal T cell expressed and activated). In the absence of the chemokines, direct
      exposure to gradients of anti-thrombin III stimulated eosinophil migration. The
      effects of anti-thrombin III were abolished by pre-treating cells with heparinase
      1, chondroitinase, sodium chlorate and anti-syndecan-4 antibodies. Syndecan-4
      gene expression in eosinophils was confirmed in PCR. In the presence of
      pentasaccharide, anti-thrombin III lost its effect on the cells. Functional
      responses were also abrogated by inhibition of protein kinase C,
      phosphatidylinositol 3-kinase and phosphodiesterase. CONCLUSION: Data indicate
      that anti-thrombin III affects eosinophil motility via the effects of its heparin
      binding site on cell surface syndecan-4. Ligation of syndecan-4 with anti
      thrombin III induces eosinophil migration and deactivates motility toward
      chemokines. These observations suggest that syndecan-4-dependent signalling may
      control eosinophil locomotion.

PMID- 15144460
TI  - Human airway submucosal glands augment eosinophil chemotaxis during rhinovirus
      infection.
AB  - BACKGROUND: Asthma exacerbations are frequently associated with rhinovirus (RV)
      infections. However, the contribution of airway submucosal gland (SMG) to
      exacerbations of asthma in RV respiratory infection has not been studied.
      OBJECTIVE: This study was undertaken to examine whether RV-infected human
      respiratory SMG cells produce pro-inflammatory cytokines and chemokines for
      eosinophils, and augment eosinophil transmigration across human airway
      epithelium. METHODS: We infected cultured human tracheal SMG cells with RV14,
      collected culture media at 1, 3, and 5 days after infection, and measured the
      chemotactic activity for eosinophils in the culture supernatant using a 48-well
      microchemotaxis chamber and a (51)Cr-labelled eosinophil transmigration assay.
      RESULTS: Exposing a confluent human tracheal SMG cell monolayer to RV14
      consistently led to infection. Human SMG cells with RV infection secreted soluble
      factors activating human eosinophil chemotaxis into the culture supernatant in a
      time-dependent manner, and the culture supernatant significantly augmented the
      transmigration of (51)Cr-labelled eosinophils through human airway epithelial
      cell layers from the basal to mucosal side. These effects were completely
      abolished by a mixture of a monoclonal antibody regulated on activation, normal T
      cells expressed and secreted (RANTES) and an antibody to granulocyte macrophage
      colony stimulating factor (GM-CSF). CONCLUSION: These results suggest that human
      respiratory SMG cells may augment eosinophil transmigration across the airway
      epithelium through the secretion of RANTES and GM-CSF after RV infection, and may
      contribute to exacerbations of asthma.

PMID- 15144461
TI  - Effect of Mycobacterium tuberculosis chaperonins on bronchial eosinophilia and
      hyper-responsiveness in a murine model of allergic inflammation.
AB  - BACKGROUND: Epidemiological evidence suggests that infection with Mycobacterium
      tuberculosis protects children against asthma. Several laboratories have shown
      that, in mouse models of allergic inflammation, administration of the whole live
      tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG),
      prevents ovalbumin (OVA)-induced pulmonary eosinophilia. OBJECTIVE: The aim of
      this study was to characterize specific M. tuberculosis molecules that are known
      to modulate immune responses to see if they affected pulmonary eosinophilia and
      bronchial hyper-responsiveness. METHODS: C57Bl/6 mice were sensitized to OVA on
      days 0 and 7 and subsequently challenged with OVA on day 14 over a 3-day period.
      Pulmonary eosinophilia and bronchial hyper-responsiveness were measured 24 h
      following the last antigen challenge. In some groups, mice were pre-treated with
      M. tuberculosis or M. tuberculosis chaperonins (Cpns)60.1, 60.2 and 10, and the
      effect of this treatment on the allergic inflammatory response to aerosolized OVA
      was established. RESULTS: We show that M. tuberculosis Cpns inhibit allergen
      induced pulmonary eosinophilia in the mouse. Of the three Cpns produced by M.
      tuberculosis, Cpn60.1, Cpn10 and Cpn60.2, the first two are effective in
      preventing eosinophilia when administered by the intra-tracheal route.
      Furthermore, the increase in airways sensitivity to inhaled methacholine
      following OVA challenge of immunized mice was suppressed following treatment with
      Cpn60.1. The allergic inflammatory response was also characterized by an increase
      in Th2 cytokines IL-4 and IL-5 in bronchoalveolar lavage fluid, which was also
      suppressed following treatment with Cpn60.1. CONCLUSION: These data show that
      bacterial Cpns can suppress eosinophil recruitment and bronchial hyper
      responsiveness in a murine model of allergic inflammation.

PMID- 15144462
TI  - Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales.
AB  - BACKGROUND: Peanuts and tree nuts are among the most common foods provoking
      severe allergic reactions including fatal anaphylaxis. However, little is known
      of the underlying genetic and immunological mechanisms involved. OBJECTIVE: Based
      on findings in other allergic diseases, we have investigated whether specific
      human leucocyte antigens (HLA) are associated with nut allergy. METHOD: Eighty
      four patients presenting at the allergy clinic with symptoms of nut allergy were
      typed for the HLA Class I (HLA-A and B) and Class II (HLA-DRB1 and DQB1) loci by
      PCR using sequence-specific primers. Carriage frequencies were compared with 82
      atopic non-nut-allergic subjects and 1798 random blood donors. RESULTS: The
      frequency of HLA-B(*)07 (28.57%) and DRB1(*)11 (15.48%) was increased in the nut
      allergic patients compared to the atopic controls (12.20% and 3.66%,
      respectively) but not when compared to the blood donors (28.86% and 10.12%).
      DRB1(*)13 and DQB1(*)06 were both increased in frequency in the nut allergy
      patients over both the atopic and blood donor controls. However, none of these
      increased frequencies were significant when corrected for the number of
      comparisons undertaken. CONCLUSION: At HLA '2-digit resolution' and with
      undifferentiated patients with nut allergy, there are no major disturbances in
      the frequency of HLA-A, B, DRB1 or DQB1 types. However, the difference in
      frequency of HLA-DRB1(*)11 between the nut allergy patients and the atopic
      controls merits further investigation as this may represent an important
      phenotypic relationship.

PMID- 15144464
TI  - Topical treatment with aqueous solutions of rofleponide palmitate and budesonide
      in a pollen-season model of allergic rhinitis.
AB  - BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug
      with a promising pre-clinical profile designed to deliver topical airway
      treatment for allergic rhinitis and asthma in a novel manner. Thus, the
      rofleponide palmitate pro-drug is designed to provide topical exposure of the
      mucosa to the inactive lipophilic drug, which would be locally metabolized to the
      more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine
      whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow
      (PIF) in a pollen-season model of allergic rhinitis and to compare any such
      effects with those of another glucocorticosteroid (i.e., budesonide). METHODS:
      During the pollen-free season, 40 patients with strictly seasonal allergic
      rhinitis received topical nasal spray treatment with an aqueous solution of
      rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg
      once daily for 10 days in a double-blind, placebo-controlled, and crossover
      study. After 3 days of drug treatment, individualized allergen challenges were
      given once daily for 7 days while the treatment continued. The washout periods
      between each of the challenge series were 2 weeks. Nasal symptoms and PIF were
      recorded in the morning and evening, as well as 10 and 20 min after each allergen
      challenge. The mean recordings obtained during the last 3 days of the allergen
      challenge series, when symptoms were established and when the treatment had
      lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments
      reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01
      0.001). There was no overall difference in efficacy between rofleponide palmitate
      400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous
      solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal
      PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide
      palmitate is similar to that of 128 microg of budesonide in the pollen-season
      model used in this study.

PMID- 15144463
TI  - No apparent association between periocular and ocular microcolonization and the
      degree of inflammation in patients with atopic keratoconjunctivitis.
AB  - BACKGROUND: The cause of the chronic inflammation in atopic keratoconjunctivitis
      (AKC), the ocular manifestation of atopic eczema/dermatitis syndrome, is largely
      unknown. OBJECTIVE: To investigate the possibility that microorganisms may be
      important in the inflammatory activity in AKC. METHODS: Fifteen patients with AKC
      participated in the study. The presence of aerobic bacteria and fungi was related
      to the severity of clinical signs, the numbers of inflammatory cells in tears and
      conjunctival biopsies, and the concentration of various cytokines in tears. In
      addition, serological evidence for IgE sensitization to Staphylococcus aureus B
      antigen and Malassezia sympodialis antigen was investigated. Twelve healthy
      subjects were included for control purposes. RESULTS: The patients exhibited
      moderate clinical signs of AKC. No relation was found between the severity of AKC
      and the presence of microorganisms, despite the fact that S. aureus was
      frequently isolated. AKC patients showed significantly higher levels of IFN
      gamma, TNF-alpha (tumour necrosis factor-alpha), IL-2, IL-4, IL-5 and IL-10 than
      controls. An association was found between conjunctival signs and the levels of
      all cytokines except IL-5. CONCLUSION: We found no evidence to suggest that
      periocular and ocular microcolonization are related to inflammatory parameters in
      AKC. However, confirmation of the present results in a longitudinal study with
      repeated clinical examinations and samplings in the same individual is required
      before the contribution of S. aureus to on-going inflammation in AKC can be
      dismissed.

PMID- 15144465
TI  - A novel promoter polymorphism in the gene encoding complement component 5
      receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three
      independent populations.
AB  - BACKGROUND: The inflammatory functions of complement component 5 (C5) are
      mediated by its receptor, C5R1, which is expressed on bronchial, epithelial,
      vascular endothelial and smooth muscle cells. A susceptibility locus for murine
      allergen-induced airway hyper-responsiveness was identified in a region syntenic
      to human chromosome 19q13, where linkage to asthma has been demonstrated and
      where the gene encoding C5R1 is localized. OBJECTIVE: The aim of this study was
      to screen for novel polymorphisms in the C5R1 gene and to determine whether any
      identified polymorphisms are associated with asthma and/or atopy and whether they
      are functional. METHODS: Single-nucleotide polymorphism (SNP) detection in the
      gene encoding C5R1 was performed by direct sequencing. Genotyping was performed
      in three populations characterized for asthma and/or atopy: (1) 823 German
      children from The Multicenter Allergy Study; (2) 146 individuals from Tangier
      Island, Virginia, a Caucasian isolate; and (3) asthma case-parent trios selected
      from 134 families (N=783) in Barbados. Functional studies were performed to
      evaluate differences between the wild-type and the variant alleles. RESULTS: We
      identified a novel SNP in the promoter region of C5R1 at position -245 (T/C).
      Frequency of the -245C allele was similar in the German (31.5%) and Tangier
      Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%;
      P=0.0039 to <0.0001). We observed no significant associations between the -245
      polymorphism and asthma or atopy phenotypes. Upon examination of the functional
      consequences of the -245T/C polymorphism, we did not observe any change in
      promoter activity. CONCLUSION: This new marker may provide a valuable tool to
      assess the risk for C5a-associated disorders, but it does not appear to be
      associated with asthma and/or atopy.

PMID- 15144466
TI  - Double-stranded RNA activates RANTES gene transcription through co-operation of
      nuclear factor-kappaB and interferon regulatory factors in human airway
      epithelial cells.
AB  - BACKGROUND: Regulated on activation, normal T cells expressed and secreted
      (RANTES) is a member of the CC chemokine family and contributes to viral-induced
      airway inflammation including exacerbations of asthma. Double-stranded RNA
      (dsRNA) is known to be synthesized during replication of many viruses and a
      ligand of Toll-like receptor 3. We hypothesized that dsRNA may mimic viral
      infection and induce RANTES expression in airway epithelial cells. OBJECTIVE: We
      first confirmed that dsRNA up-regulated RANTES mRNA and protein synthesis in the
      airway epithelial cells. We next focused our studies on the transcriptional
      regulation of RANTES. METHODS: Airway epithelial cell line BEAS-2B and normal
      human bronchial epithelial cells were used in vitro study. Levels of RANTES mRNA
      and protein expression were determined with RT-PCR and ELISA. Mechanisms of
      transcriptional regulation were assessed by electrophoretic mobility shift assay
      and dual luciferase assay using RANTES promoter-luciferase reporter plasmids.
      RESULTS: Activation of nuclear factor-kappaB (NF-kappaB) was confirmed by nuclear
      protein binding to a DNA probe derived from the RANTES promoter. Activity of the
      RANTES promoter was increased by dsRNA. The stimulation with dsRNA was partially
      inhibited in plasmids mutated at either of the binding sites for NF-kappaB or IFN
      regulatory factors (IRFs). When both sites were mutated, the activation was
      totally abrogated. CONCLUSION: These results imply that dsRNA activates NF-kappaB
      and IRFs and these transcription factors activate transcription of the RANTES
      promoter and its protein expression in airway epithelial cells.

PMID- 15144467
TI  - Does previous infection protect against atopic eczema and recurrent wheeze in
      infancy?
AB  - BACKGROUND: Frequent infection in infancy and early childhood has been
      hypothesized to explain the low prevalence of asthma and other atopic disease
      among children in developing countries (the so-called 'hygiene hypothesis'), but
      the low prevalence in Eastern Europe remains unexplained. OBJECTIVE: To test the
      hygiene hypothesis in the Republic of Belarus by examining the relationship
      between gastrointestinal (GI) and respiratory infection and two potentially
      atopic outcomes in the first 12 months of life: atopic eczema and recurrent
      wheeze. METHODS; We carried out two case-control studies nested within a large
      (n=17 046) randomized trial in Belarus, with cases defined as (1) first
      occurrence of atopic eczema (n=819) and (2) second episode of wheezing (n=112).
      Incidence density sampling was used to select four matched controls born within 1
      month at the same hospital as the case. Exposure was defined as one or more
      episodes of GI or respiratory infection (examined separately) with onset >7 days
      before onset of the case's atopic outcome. Analyses controlled for family atopic
      history, duration of exclusive breastfeeding, sex, birth weight, maternal
      education, and (for recurrent wheeze) maternal smoking. RESULTS: For atopic
      eczema, prior GI infection occurred in 7.4% of cases vs. 6.0% of controls
      [adjusted OR=1.27 (0.94-1.72)] and prior respiratory infection in 35.2% vs. 32.6%
      [adjusted OR=1.14 (95% CI=0.94-1.37)]. For recurrent wheeze, prior GI infection
      occurred in 9.8% of cases vs. 7.4% of controls [adjusted OR=1.30 (0.60-2.82)].
      CONCLUSION: Our results do not support the hypothesis that infection protects
      against atopic eczema or recurrent wheezing in the first 12 months of life.

PMID- 15144468
TI  - Polymorphisms of the ADAM33 gene are associated with accelerated lung function
      decline in asthma.
AB  - BACKGROUND: Asthma is a genetically complex disease characterized by respiratory
      symptoms, intermittent airway obstruction and airway hyper-responsiveness due to
      airway inflammation and remodelling. The ADAM33 gene is associated with asthma
      and airway hyper-responsiveness and is postulated as a gene for airway
      remodelling. OBJECTIVE: To investigate whether polymorphisms of the ADAM33 gene
      are associated with accelerated lung function decline in patients with asthma.
      METHODS: In a cohort of 200 asthma patients followed over 20 years, eight single
      nucleotide polymorphisms of the ADAM33 gene were analysed to estimate their
      effect on annual FEV(1) decline. RESULTS: The rare allele of the S_2 polymorphism
      was significantly associated with excess decline in FEV(1) (P<0.05). CONCLUSION:
      These findings suggest that a variant in ADAM33 is not only important in the
      development of asthma but also in disease progression, possibly related to
      enhanced airway remodelling.

PMID- 15144469
TI  - Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed
      by skin tests and double-blind food challenges.
AB  - BACKGROUND: The effect of birch-pollen immunotherapy (IT) on cross-reactive food
      allergies is controversial. OBJECTIVE: The aim of this study was to investigate
      the effect of birch-pollen IT on apple allergy and to evaluate recombinant
      allergens and double-blind placebo-controlled food challenges (DBPCFCs) as
      monitoring tools. METHODS: Twenty-five adult birch-pollen- and apple-allergic
      patients were randomly divided into two groups, either receiving birch-pollen IT
      or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple,
      natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT)
      were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1).
      Clinical outcome was evaluated by DBPCFC. CD4(+)CD25(+) regulatory T cells
      (Tregs) were isolated from peripheral blood and tested in functional assays.
      RESULTS: Birch-pollen IT resulted in a significant decrease of SPT reactivity for
      rBet v 1 (30-fold) and rMal d 1 (10-fold) already after 3 months. IgG4 antibodies
      were potently induced against Bet v 1, displaying cross-reactivity to Mal d 1.
      Visual analogue scale scores decreased >10-fold in 9/13 patients of the IT group,
      with three patients converting to negative. In the control group, no decrease was
      observed. Birch-pollen IT did not lead to detectable changes in the number or
      function of the CD4(+)CD25(+) Tregs. CONCLUSIONS: This trial supports the claims
      that birch-pollen IT also decreases allergy to foods containing Bet v 1
      homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful
      tools for monitoring the effect of birch-pollen IT on linked food allergies.

PMID- 15144470
TI  - Roles of major oligosaccharides on Cry j 1 in human immunoglobulin E and T cell
      responses.
AB  - BACKGROUND: We have demonstrated that carbohydrates in Cry j 1, the major
      allergen of Cryptomeria japonica pollen, play a major role in promoting Cry j 1
      specific Th2 response. However, little is known as to whether the carbohydrates
      directly participate in allergic responses. OBJECTIVE: We sought to determine
      whether Cry j 1-related oligosaccharides function as IgE and/or T cell epitopes.
      In addition, the regulatory effect of Cry j 1-related oligosaccharide on Cry j 1
      specific T cell responses was investigated. METHODS: Two monovalent
      oligosaccharides largely found on Cry j 1, Manalpha1-6(Manalpha1-3)(Xylbeta1
      2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc (M3FX), and GlcNAcbeta1-2Manalpha1
      6(GlcNAcbeta1-2Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc
      (GN2M3FX) were prepared. Manalpha1-2Manalpha1-6(Manalpha1-2Manalpha1-3)Manalpha1
      6(Manalpha1-2Manalpha1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc (M9A) was used
      as control. Competitive inhibition ELISA for Cry j 1-specific IgE was performed
      using these oligosaccharides as inhibitors. In addition, T cell lines specific
      for Cry j 1 or purified protein derivative of Mycobacterium tubecurosis (PPD)
      were established, and cellular responses against these oligosaccharides were
      investigated in the presence or absence of the respective antigens. RESULTS:
      Overall, neither M3FX nor GN2M3FX displayed inhibitory effect on the binding
      between IgE and Cry j 1. In addition, M3FX did not by itself stimulate Cry j 1 or
      PPD-specific T cells. However, M3FX significantly inhibited Cry j 1-induced
      proliferation and IL-4 production in Cry j 1-specific T cells. Such an inhibitory
      effect was not seen in PPD-specific T cell responses. CONCLUSION: These results
      suggest that Cry j 1-related oligosaccharides are not major epitopes for IgE or T
      cells. However, these oligosaccharides have a novel potential to inhibit Cry j 1
      specific T cell responses selectively.

PMID- 15144471
TI  - Prevalence and associated factors of atopic dermatitis symptoms in rural and
      urban Ethiopia.
AB  - BACKGROUND: Allergic diseases, including atopic dermatitis (AD), are increasingly
      becoming a clinical problem in developing countries. OBJECTIVE: We investigated
      the prevalence of AD symptoms and the effects of potential environmental
      aetiologies in rural and urban areas of Jimma in southwestern Ethiopia. METHODS:
      Information on allergic disease symptoms and lifestyle factors was gathered in an
      interviewer-led cross-sectional questionnaire-based population survey of 9844
      urban and 3032 rural participants of all ages. A one-in-four subsample underwent
      skin prick testing for hypersensitivity to Dermatophagoides pteronyssinus, mixed
      threshings, and aspergillus. RESULTS: Around 95% of those eligible took part in
      the survey. Lifetime cumulative prevalence of AD symptoms was generally low with
      an overall prevalence of 1.2%, but was higher in the urban (1.5%) than in the
      rural area (0.3%; odds ratio (OR)=4.45 [95% CI 2.34-8.47]). AD symptoms were
      strongly associated with wheeze (adjusted OR=22.03 [15.45-31.42]) and rhinitis
      symptoms (61.94 [42.66-89.95]). Of several environmental exposures assessed,
      residence in a house made of brick (rather than mud) walls with wooden (rather
      than clay) floor, exposure to cigarette smoke as a child, having lived outside of
      Jimma in the past, and being of the Tigrean ethnic group were associated with an
      increased risk of AD symptoms. CONCLUSION: Although the overall prevalence of AD
      symptoms was low in this Ethiopian population, a marked urban-rural gradient was
      evident. Lifestyle factors linked to urbanization were associated with an
      increased risk of AD symptoms.

PMID- 15144473
TI  - In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo
      controlled, crossover trial.
AB  - BACKGROUND: In people with a history of sting allergy, only prior reaction
      severity and older age are known to predict subsequent reaction risk.
      Furthermore, no diagnostic test other than a deliberate sting challenge has been
      found to identify people in whom venom immunotherapy (VIT) has been unsuccessful.
      OBJECTIVE: We aimed to assess the utility of a number of in vitro tests to
      diagnose venom allergy and to monitor immunotherapy. METHODS: During a double
      blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT
      the following venom-specific tests were performed at enrolment, and at completion
      of treatment prior to a diagnostic sting challenge; leucocyte stimulation index
      (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene
      release test (LRT) and basophil activation test (BAT). Intradermal venom skin
      testing (VST) was also performed at trial entry. RESULTS: Only VST and HRT
      identified those at risk of sting anaphylaxis in the placebo group. Although IgE
      RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with
      intradermal VSTs, they did not predict sting challenge outcome. After successful
      VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST
      increased and a natural decline in HRT reactivity was reversed. A confounding
      seasonal affect on laboratory results was suspected. CONCLUSION: The HRT warrants
      further assessment for diagnosis of venom allergy. Uninformative performance of
      the commercially available LRT and BAT tests may be due to pre-incubation with IL
      3. None of the tests evaluated appear to be reliable markers of successful VIT.

PMID- 15144472
TI  - Increased macrophage-derived chemokine in exhaled breath condensate and plasma
      from children with asthma.
AB  - BACKGROUND: Type 2 helper T lymphocyte-specific chemokines including macrophage
      derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) and
      eotaxin are important mediators for allergic airway inflammation. OBJECTIVE: We
      investigated whether these chemokines can be detected in exhaled breath
      condensate (EBC) and their relation to childhood asthma. METHODS: Asthmatics
      recruited from paediatric clinics of a university teaching hospital were
      classified into intermittent asthma (IA) and persistent asthma (PA) according to
      Global Initiative for Asthma guidelines. EBC was collected by a disposable
      collection kit, whereas fractional exhaled nitric oxide (FENO) was measured by a
      chemiluminescence analyser. Concentrations of MDC, TARC and eotaxin in both EBC
      and plasma were measured using sandwich enzyme immunoassay. The intra-subject
      reproducibility of exhaled chemokine measurements was determined by co-efficients
      of variation (CV). RESULTS: Forty-eight patients with PA, 36 children with IA and
      18 controls were recruited. MDC and eotaxin were present in EBC from nearly all
      subjects, whereas TARC could be measured in EBC from 33 (32%) subjects only. The
      median MDC concentration in EBC was higher in PA (117 pg/mL) as compared with IA
      (106 pg/mL) and controls (105 pg/mL; P=0.003 for both). The median plasma MDC
      concentration in PA (648 pg/mL) was also higher than that in IA (520 pg/mL;
      P=0.002) and controls (490 pg/mL; P=0.008). The median plasma TARC concentration
      was also increased in PA as compared with IA (72 pg/mL vs. 35 pg/mL; P=0.004).
      MDC concentrations in EBC were lower in patients with PA who received high-dose
      inhaled corticosteroid (P=0.005). FENO was significantly higher in asthmatics
      than controls (P<0.0001), but it was not associated with chemokines in EBC or
      plasma. The mean (range) CV for measuring MDC, TARC and eotaxin in EBC (n=6) were
      5.5 (2.0-7.2%), 8.8 (3.6-14.4%) and 5.2 (2.8-7.9%), respectively. CONCLUSIONS:
      Our results suggest that MDC in EBC and MDC and TARC in plasma are increased in
      children with PA as compared with IA or control. MDC concentrations in EBC are
      suppressed in patients on high-dose inhaled corticosteroid treatment.

PMID- 15144474
TI  - Genetic predisposition to wheeze following respiratory syncytial virus
      bronchiolitis.
AB  - BACKGROUND: The nature of the association between severe respiratory syncytial
      virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous
      study, we showed that genetic variation in the IL-8-promoter region is associated
      with susceptibility to severe bronchiolitis. OBJECTIVE: The purpose of this study
      was to assess the association between wheezing post-bronchiolitis and the genetic
      variant of IL-8 gene. METHODS: We collected data from 134 children who had
      suffered from bronchiolitis, enrolled in our previous study. The occurrence of
      wheezing post-bronchiolitis was recorded from a questionnaire sent by post. The
      association between the genotype and wheezing phenotype was assessed by family
      based and case-control approaches. RESULTS: Family-based association showed that
      the IL-8 variant was transmitted significantly more often than expected in the
      children who wheezed after the episode of bronchiolitis (transmission=56%,
      P=0.02). This effect was not observed in the group of children who had
      bronchiolitis but did not go on to wheeze. Moreover, the variant was
      significantly more frequent in post-bronchiolitis wheezers compared with the
      general population (odds ratio=1.6, 95% confidence interval 1.0-2.6). CONCLUSION:
      These preliminary results suggest that there is a genetic predisposition to
      wheeze following severe RSV bronchiolitis.

PMID- 15144475
TI  - Induction of eotaxin production by interleukin-4, interleukin-13 and
      lipopolysaccharide by nasal fibroblasts.
AB  - BACKGROUND: There is growing evidence that eotaxin is a key mediator in the
      development of tissue eosinophilia. Fibroblasts are a major source of eotaxin.
      The severity of diseases with eosinophilic inflammation like nasal polyposis,
      atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF
      beta are expressed locally, was shown to correlate with bacterial factors such as
      lipopolysaccharide (LPS) rather than allergen. OBJECTIVE: We examined eotaxin
      production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in
      combination with LPS, and the effect of TGF-beta(1) on it. Moreover, we compared
      the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung
      or skin fibroblasts. METHODS: Fibroblast lines were established from human biopsy
      tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of
      eotaxin in the supernatants was measured by ELISA. RESULTS: IL-4, but not IL-13,
      synergized with LPS to produce eotaxin in a dose- and time-dependent manner.
      Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any
      effect. But when IL-4 and LPS were added together, synergy for eotaxin production
      was observed. Moreover, this synergy was observed in nasal and skin fibroblasts,
      but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was
      modulated by TGF-beta(1). CONCLUSION: These results suggest that a co-stimulus
      like LPS is necessary for IL-4 to make a strong induction of eotaxin in
      eosinophilic inflammations such as nasal polyposis. Modulation by TGF-beta(1) may
      have important implications for the development of eosinophilic inflammation.

PMID- 15144476
TI  - Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acid anhydrides.
AB  - BACKGROUND: Organic acid anhydrides are low molecular weight industrial
      chemicals, able to cause rhinoconjunctivitis and asthma associated with specific
      IgE against hapten-carrier protein conjugate. Only a proportion of exposed
      workers develop IgE-associated allergy to acid anhydrides. OBJECTIVE: We
      determined whether genetic susceptibility, in particular, HLA Class II alleles
      may be a risk factor. METHODS: We undertook HLA typing in 52 cases who had
      confirmed specific IgE and in 73 referents matched on site, age and duration of
      acid anhydride exposure identified in cross-sectional studies of workers exposed
      to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and
      methyltetrahydrophthalic (MTHPA) anhydrides. RESULTS: The linked alleles DQ5
      (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0;
      95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5,
      DQB1(*)0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). CONCLUSION:
      DQB1(*)05 gene confers susceptibility to develop specific IgE antibodies against
      HHPA, MHHPA and a non-significant trend with MTHPA. DQB1(*)0501 is protective for
      other low molecular chemical sensitizers (isocyanates and plicatic acid) which
      may indicate varying affinities for the corresponding specific class II
      molecules.

PMID- 15144477
TI  - Late eczematous reactions to food in children with atopic dermatitis.
AB  - BACKGROUND: Food allergy is a common problem in patients with atopic dermatitis
      (AD), particularly in children. While immediate reactions to food are well
      characterized, the importance of food as a provocation factor for late eczematous
      reactions has been a subject of debate for several decades. OBJECTIVE: To
      investigate the importance of food for the induction of late eczematous reactions
      in children with AD and to correlate the clinical outcome to the results of
      specific IgE determinations and atopy patch tests (APTs). METHODS: One hundred
      and six double-blind placebo-controlled food challenges (DBPCFCs) to cow's milk,
      hen's egg, wheat and soy in 64 children with AD (median age 2 years) were
      analysed retrospectively. Total and food-specific IgE were determined by CAP RAST
      FEIA and APTs with native foodstuff were performed. The diagnostic values of
      specific IgE and APT results were calculated. RESULTS: Forty-nine (46%) of the
      challenges were related to a clinical reaction. An exacerbation of AD (late
      eczematous reaction) commonly occurred 24 h after the ingestion of food. Isolated
      late eczematous reactions were seen in 12% of all positive challenges. Forty-five
      percent of the positive challenges were associated with late eczematous
      responses, which followed immediate-type reactions. The sensitivity of food
      specific IgE and the APT was 76% and 70%, respectively. Specific IgE and APT were
      often false positive, which resulted in low positive predictive values (64% and
      45%, respectively). CONCLUSIONS: Late eczematous reactions may often be observed
      upon food challenge in children with AD. Due to the poor reliability of food
      specific IgE and APT results DBPCFCs have still to be regarded as the gold
      standard for the appropriate diagnosis of food responsive eczema in children with
      AD.

PMID- 15144478
TI  - Transition to child care: associations with infant-mother attachment, infant
      negative emotion, and cortisol elevations.
AB  - Seventy 15-month-old infants were studied at home before starting child care,
      during adaptation (mothers present) and separation (first 9 days without mothers)
      phases, and 5 months later. Security of infant-mother attachment was assessed
      before and 3 months after child care began. In the separation phase, salivary
      cortisol rose over the first 60 min following the mothers' departures to levels
      that were 75% to 100% higher than at home. Compared with insecure infants, secure
      infants had markedly lower cortisol levels during the adaptation phase and higher
      fuss and cry levels during the separation phase, and their fuss and cry levels
      were significantly correlated with their cortisol levels. Attachments remained
      secure or became secure if mothers spent more days adapting their children to
      child care.

PMID- 15144479
TI  - Genetic and environmental processes in young children's resilience and
      vulnerability to socioeconomic deprivation.
AB  - Some children exposed to socioeconomic (SES) deprivation are resilient and
      function better than expected, given the level of deprivation they have
      experienced. The present study tested genetic and environmental contributions to
      young children's resilience and vulnerability to SES deprivation. Children's
      resilience was assessed by the difference between their actual score and the
      score predicted by their level of SES deprivation in the E-Risk Study, an
      epidemiological cohort of 1,116 five-year-old twin pairs. Consistent with
      previous research, results showed that maternal warmth, stimulating activities,
      and children's outgoing temperament appeared to promote positive adjustment in
      children exposed to SES deprivation. Findings add new information by
      demonstrating that resilience is partly heritable and that protective processes
      operate through both genetic and environmental effects.

PMID- 15144480
TI  - The time to talk: the influence of the timing of adult-child talk on children's
      event memory.
AB  - To investigate the influence of the nature and timing of adult-child talk on
      event recall, this study engaged 63 three-year-olds and 65 five-year-olds in a
      staged event and interviewed them 2 weeks later. Children were assigned to 1 of 4
      conditions: elaborative pre-, during-, and post-talk, and empty talk (during the
      event). Children in the elaborative, relative to the empty, talk conditions made
      fewer errors. Furthermore, post-talk had the greatest influence on correct
      recall, although for the 5-year-olds, during-talk was also facilitative. Recall
      was enhanced to a greater extent by the child's contribution to the talk,
      relative to that of the adult. The findings contribute to an understanding of the
      mechanisms by which adult-child conversations influence recall.

PMID- 15144481
TI  - Children's thinking about diversity of belief in the early school years:
      judgments of relativism, tolerance, and disagreeing persons.
AB  - Children's thinking about diversity of belief in 4 realms--morality, taste,
      facts, and ambiguous facts--was examined. Ninety-six participants (ages 5, 7, and
      9) were interviewed about beliefs different from their own that were endorsed by
      characters with different status; their judgments of relativism, tolerance, and
      disagreeing persons were assessed. Five-year-olds made fewer relative and
      tolerant judgments than 7- and 9-year-olds. Nevertheless, participants of all
      ages organized their judgments according to the realm of diversity, thought that
      some beliefs are relative and some are nonrelative, and made tolerant judgments
      of some divergent beliefs (and their proponents) but not of others. The findings
      suggest that, in the early school years, children have multiple and well
      differentiated perspectives on belief diversity.

PMID- 15144482
TI  - Children's developing knowledge of the relationship between mental awareness and
      pretense.
AB  - This study investigated 3- and 4-year-old's understanding of the relationship
      between pretense and mental awareness. In Experiments 1 and 2, only a subset of 4
      year-olds recognized that sleeping characters and characters ignorant of their
      appearance were not pretending. However, these experiments had certain linguistic
      demands, which potentially influenced performance. In Experiments 3, these demand
      characteristics were reduced; under these circumstances, 3- and 4-year-olds
      recognized that pretenders were aware of their actions or appearance. However,
      Experiment 4 showed that even using this modified procedure, 3- and 4-year-olds
      do not completely understand the relationship between pretense and awareness.
      These data support the hypotheses that by the age of 4, children have some, but
      not a complete, understanding of the relationship between pretense and mental
      awareness.

PMID- 15144483
TI  - Forced to choose: some determinants of racial identification in multiracial
      adolescents.
AB  - This paper categorizes multiracial youth (N=1,496) ages 14 to 19 and compares
      them with each other and with monoracial youth on identity development measures.
      The multiracial categories used here are derived from youths' reports of their
      own and their parents' race(s). Comparisons are made within groups of multiracial
      respondents who make different choices among single-race categories. Results show
      differences between subgroups in strength and importance of ethnic identity, self
      esteem, and perceptions of ethnic discrimination. Multinomial logistic regression
      shows further that physiognomy, ethnic identity, and race of coresident parent(s)
      are significantly associated with reported race. Also related to racial
      identification among part-Hispanic youth are the racial distribution and
      socioeconomic status of their neighborhoods and the racial distributions of their
      schools.

PMID- 15144484
TI  - Children's strategies and goals in response to help-giving and help-seeking tasks
      within a friendship.
AB  - The present research tested whether children's responses to help-giving and help
      seeking friendship tasks predicted how many friends they had and the quality of
      their best friendship. Fifth-grade children (N=511; typically 10 or 11 years old)
      responded to vignettes in which they could either give help to a friend or seek
      help from a friend. Children's strategies and goals in both contexts were
      significantly correlated with the number of friends children had. Responses in
      the help-giving context but not in the help-seeking context were significantly
      associated with friendship quality. Although gender differences in strategies and
      goals were found, strategies and goals were related to the number of friends and
      friendship quality for both boys and girls.

PMID- 15144485
TI  - Children's achievement moderates the effects of mothers' use of control and
      autonomy support.
AB  - Two studies investigated the effects of parents' control and autonomy support on
      low- and high-achieving children. In Study 1, mothers' (N=110) involvement with
      children (7 to 10 years old) in the context of a challenging task was observed.
      During this interaction, mothers' control predicted diminished engagement and
      their autonomy support predicted enhanced performance for low-achieving children
      more than for high-achieving children. In Study 2, mothers' (N=121) responses to
      children's (9 to 12 years old) failure were assessed with a daily checklist.
      Children's grades were obtained at this time and 6 months later. Mothers'
      controlling responses predicted decreased performance and their autonomy
      supportive responses predicted increased performance over time for low achievers
      more than for high achievers.

PMID- 15144486
TI  - Parental influences on adolescent problem behavior: revisiting Stattin and Kerr.
AB  - High school students (approximately 14-18 years old; N=2,568) completed
      questionnaires in which they reported on their involvement in substance use and
      delinquency, and their perceptions of parental warmth, control, monitoring, and
      knowledge. Three alternative models were compared describing the nature of
      relations among these variables. Problem behavior was best predicted by a model
      that included indirect effects of warmth, control, and monitoring (all by way of
      parental knowledge), as well as direct effects of control and monitoring.
      Analyses are framed and findings are discussed with reference to recent work by
      Stattin and Kerr (2000; Kerr & Stattin, 2000) on the measurement and meaning of
      parental monitoring.

PMID- 15144488
TI  - Parental control of the personal domain and adolescent symptoms of
      psychopathology: a cross-national study in the United States and Japan.
AB  - One hundred seventy U.S. (M=16.1 years) and 125 middle-class Japanese (M=16.6
      years) adolescents completed a questionnaire assessing perceptions of who
      (adolescent or parent) controls the personal, conventional, prudential, and
      overlapping domain behaviors of the adolescent. Participants also completed an
      inventory assessing self-reported psychological symptoms. Adolescents in both
      countries indicated that they should have more say over personal issues and that
      parents should have more say over conventional and prudential issues. Self
      reports of internalizing symptoms were positively correlated with amount of
      perceived control over personal issues for U.S. and Japanese students and for
      parental control over overlapping domain issues for Japanese students. There were
      no associations between parental control of conventional or prudential behaviors
      and psychological symptoms.

PMID- 15144487
TI  - Physiological reactivity, social support, and memory in early childhood.
AB  - The interactive effects of physiological reactivity and social support on
      children's memory were examined. Four- to 6-year-olds completed a laboratory
      protocol during which autonomic responses and salivary cortisol were measured.
      Memory was assessed shortly afterward and 2 weeks later. During the second
      interview, children were questioned by a supportive or nonsupportive interviewer.
      Few significant relations emerged between reactivity and children's short-term
      memory. Following a 2-week delay, cortisol reactivity was associated with poorer
      memory and autonomic reactivity was associated with increased accuracy among
      children questioned in a supportive manner but decreased accuracy among children
      questioned in a nonsupportive manner. Results question traditional
      conceptualizations of reactivity as a risk factor and instead suggest that
      reactivity may only confer risk in certain environmental contexts.

PMID- 15144489
TI  - Moving toward and away from the world: social approach and avoidance trajectories
      in anxious solitary youth.
AB  - This investigation tested the person-by-environment hypothesis that the joint
      influence of behavioral vulnerability (anxious solitude) and interpersonal
      adversity (peer exclusion) predicts heightened social avoidance and depression
      over time. The study assessed 519 fifth and sixth graders 3 times during 1 year.
      Teachers reported social behavior and peer exclusion; youth reported depression.
      As hypothesized, anxious solitary youth displayed maintenance or exacerbation of
      social avoidance and depression in the context of high exclusion, but increased
      social approach and less depression in the context of low exclusion. Some effects
      were moderated by sex. The interaction of behavioral vulnerability and peer
      exclusion was more consistently linked to adjustment changes in anxious solitary
      youth than in youth with other behavioral profiles.

PMID- 15144490
TI  - Attachment status in children prenatally exposed to cocaine and other substances.
AB  - Attachment status of children exposed in utero to cocaine, opiates, and other
      substances was examined at 18 months (n=860) and 36 months (n=732) corrected age.
      Children exposed to cocaine and opiates had slightly lower rates of attachment
      security (but not disorganization), and their insecurity was skewed toward
      ambivalent, rather than avoidant, strategies. Continued postnatal alcohol use was
      associated with higher rates of insecurity and disorganization at 18, but not 36,
      months of age. Stability of attachment across the 18-month period was barely
      above chance expectation. Attachment status at 18 months was associated with
      child temperament and caregiver-child interaction; at 36 months, attachment was
      associated with child temperament, child behavior problems, and caregivers'
      parenting self-esteem.

PMID- 15144491
TI  - Parental guidance in preschoolers' understanding of spatial-graphic
      representations.
AB  - This research was designed to observe whether parents guide their children's
      understanding of spatial-graphic representations and, if so, to describe the
      quality of the strategies they use. Parents read a picture book to their
      preschoolers (3 or 5 years, N=31) and children completed spatial-graphic
      comprehension tasks. Observational data revealed a range of creative behaviors
      used to address the book's spatial-graphic challenges. The incidence and quality
      of parental spatial-graphic behaviors were significantly related to 5-year-old
      children's performance on spatial-graphic measures. These findings, as well as
      the paucity of parent attention to aesthetics or graphic production techniques,
      are discussed in relation to representational development and educational
      practice.

PMID- 15144492
TI  - Development of subordinate-level categorization in 3- to 7-month-old infants.
AB  - Visual preference procedures were used to investigate development of perceptually
      based subordinate-level categorization in 3- to 7-month-old infants. Experiments
      1 and 2 demonstrated that 3- to 4-month-olds did not form category
      representations for photographic exemplars of subordinate-level classes of cats
      and dogs (i.e., Siamese vs. Tabby, Beagle vs. Saint Bernard). Experiments 3
      though 5 showed that 6- and 7-month-olds formed a category representation for
      Tabby that excluded Siamese and a category representation for Saint Bernard that
      excluded Beagle, but they did not form a category representation for Siamese that
      excluded Tabby or a category representation for Beagle that excluded Saint
      Bernard. The findings are consistent with a differentiation-driven view of early
      perceptual category development from global to basic to subordinate levels.

PMID- 15144494
TI  - Should you ask a fisherman or a biologist?: Developmental shifts in ways of
      clustering knowledge.
AB  - Individuals can infer what others are likely to know by clustering knowledge
      according to common goals, common topics, or common underlying principles.
      Although young children are sensitive to underlying principles, that manner of
      clustering might not prevail when other viable means are presented. Two studies
      examined how a sample of 256 children at ages 5, 7, 9, and 11 decide how to
      generalize another person's knowledge when goals, topics, and principles are put
      in conflict. In both studies, younger children preferred generalizing according
      to goals and topics, whereas older children preferred clustering based on
      principles related to disciplines. The most naturalistic ways of envisioning how
      knowledge is clustered in the minds of others therefore seems to change
      significantly during the elementary school years.

PMID- 15144493
TI  - The Strong African American Families Program: translating research into
      prevention programming.
AB  - A randomized prevention trial contrasted families who took part in the Strong
      African American Families Program (SAAF), a preventive intervention for rural
      African American mothers and their 11-year-olds, with control families. SAAF is
      based on a contextual model positing that regulated, communicative parenting
      causes changes in factors protecting youths from early alcohol use and sexual
      activity. Parenting variables included involvement-vigilance, racial
      socialization, communication about sex, and clear expectations for alcohol use.
      Youth protective factors included negative attitudes about early alcohol use and
      sexual activity, negative images of drinking youths, resistance efficacy, a goal
      directed future orientation, and acceptance of parental influence. Intervention
      induced changes in parenting mediated the effect of intervention group influences
      on changes in protective factors over a 7-month period.

PMID- 15144495
TI  - African American late adolescents' relationships with parents: developmental
      transitions and longitudinal patterns.
AB  - Five-year longitudinal patterns and the influence of developmental transitions on
      76 middle-class African American late adolescents' (M=18.43 years) relationships
      with parents were examined. Late adolescents were closer to mothers than to
      fathers. Controlling for age, late adolescent females who had left home reported
      less negative relationships with mothers than did adolescents living at home or
      in transition to leaving home, and late adolescent females living at home
      reported more intense conflicts with parents 3 years earlier than did boys living
      at home and girls living away. Earlier attachment led to more attached and
      supportive relationships with both parents and less negative interactions with
      mothers in late adolescence. Stable father presence also influenced more positive
      relationships with fathers.

PMID- 15144496
TI  - Out-of-school care and problem behavior trajectories among low-income
      adolescents: individual, family, and neighborhood characteristics as added risks.
AB  - Using a developmental systems approach, this study considered longitudinal links
      between adolescents' out-of-school care experiences and behavioral trajectories
      within a random sample of 819 adolescents ages 10 to 14 years at Wave 1 from low
      income, urban families. Multiple aspects of context were considered, including
      the location, supervision, and structure of adolescents' care arrangements, as
      well as parenting practices and perceived neighborhood environments. Regression
      models indicated that out-of-home care, whether supervised or unsupervised,
      showed modest longitudinal relations with heightened rates of delinquency, drug
      and alcohol use, and school problems. Out-of-home care was linked with
      particularly deleterious outcomes for adolescents with high earlier rates of
      behavior problems, low parental monitoring, and low perceived neighborhood
      collective efficacy.

PMID- 15144497
TI  - Family interdependence and academic adjustment in college: youth from immigrant
      and U.S.-born families.
AB  - This study is an examination of family interdependence and its implications for
      academic adjustment among late adolescents and young adults in college (18 to 25
      years). Survey data and university records were collected on 998 American youth
      with Asian Pacific, Latino, African/Afro-Caribbean, and European backgrounds.
      Results indicate that Asian Pacific Americans placed more importance on family
      interdependence than did European Americans. Across all panethnic groups, youth
      with immigrant parents placed greater emphasis on family interdependence than did
      youth with U.S.-born parents. The study distinguished between family
      interdependence attitudes and behaviors and found that they had counteracting
      influences on academic adjustment: Family obligation attitudes contributed to
      greater academic motivation among youth from immigrant as compared with U.S.-born
      families, but greater behavioral demands detracted from achievement.

PMID- 15144498
TI  - Extra-cellular matrix in vascular networks.
AB  - The vascular network is a series of linked conduits of blood vessels composed of
      the endothelium, a monolayer of cells that adorn the vessel lumen and surrounding
      layer(s) of mesenchymal cells (vascular smooth muscle, pericytes and
      fibroblasts). In addition to providing structural support, the mesenchymal cells
      are essential for vessel contractility. The extracellular matrix is a major
      constituent of blood vessels and provides a framework in which these various cell
      types are attached and embedded. The composition and organization of vascular
      extracellular matrix is primarily controlled by the mesenchymal cells, and is
      also responsible for the mechanical properties of the vessel wall, forming
      complex networks of structural proteins which are highly regulated. The
      extracellular matrix also plays a central role in cellular adhesion,
      differentiation and proliferation. This review examines the cellular and
      extracellular matrix components of vessels, with specific emphasis on the
      regulation of collagen type I and implications in vascular disease.

PMID- 15144499
TI  - Cytotoxicity of lavender oil and its major components to human skin cells.
AB  - Lavender (Lavandula angustifolia) oil, chiefly composed of linalyl acetate (51%)
      and linalool (35%), is considered to be one of the mildest of known plant
      essential oils and has a history in wound healing. Concerns are building about
      the potential for irritant or allergenic skin reactions with the use of lavender
      oil. This study has demonstrated that lavender oil is cytotoxic to human skin
      cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25%
      (v/v) in all cell types tested (HMEC-1, HNDF and 153BR). The major components of
      the oil, linalyl acetate and linalool, were also assayed under similar conditions
      for their cytotoxicity. The activity of linalool reflected that of the whole oil,
      indicating that linalool may be the active component of lavender oil. Linalyl
      acetate cytotoxicity was higher than that of the oil itself, suggesting
      suppression of its activity by an unknown factor in the oil. Membrane damage is
      proposed as the possible mechanism of action.

PMID- 15144500
TI  - The influence of antisense oligonucleotides against STAT5 on the regulation of
      normal haematopoiesis in a bone marrow model.
AB  - Cytokines and growth factors that take part in the regulation of haematopoietic
      cell development activate many signalling pathways in target cells. The STAT5
      (signal transducers and activators of transcription) proteins are members of a
      family of signal transducers and activators of transcription that can be
      activated after cytokine stimulation. Their binding to promoters of different
      genes influences cell proliferation, differentiation and survival. It is
      suggested that they play an important role in haematopoiesis, however, the
      question of the real function of STAT5 proteins requires further examination. The
      aim of our study was to investigate the role of STAT5 in the proliferation and
      apoptosis of normal haematopoietic bone marrow cells derived from heparinized
      cadaveric organ donors (HCOD). We applied antisense oligodeoxynucleotides (ODNs)
      to block STAT5A and STAT5B at the mRNA level and the reverse transcription
      polymerase chain reaction method to study STAT5 mRNA expression in the cells
      after incubation with ODNs. Moreover, we performed Western blot analysis of the
      STAT5A protein after exposure to antisense STAT5A. We analysed the clonogenicity
      of the colony-forming unit of granulocytes-macrophages and the burst-forming unit
      of erythrocytes in methylcellulose cultures according to the type and the dose of
      ODNs. We also examined apoptosis induced in bone marrow mononuclear and CD34(+)
      cells by employing annexin V staining and the TUNEL method using flow cytometry
      (FACScan). We found that the perturbation of STAT5 expression decreased the
      clonogenicity of bone marrow haematopoietic cells. However, we did not observe
      any significant increase in the percentage of apoptotic cells after incubation
      with antisense ODNs. It was concluded that the STAT5 proteins play a significant
      role in the proliferation of human bone marrow cells harvested from HCOD. These
      proteins might be critical in the regulation of haematopoiesis, especially under
      stress conditions.

PMID- 15144501
TI  - Stability of cultured dental follicle cells.
AB  - Because the dental follicle is required for tooth eruption, establishment of
      dental follicle cell (DFC) lines is needed for experimentation to determine how
      the cells regulate eruption. Thus, it is critical that the follicle cells in
      culture remain stable and neither become transformed nor differentiate. To
      determine the stability of rat DFC cultures in terms of exhibiting contact
      inhibition of growth when confluent (no transformation), DFC at different
      passages were analysed using flow cytometry. Gene expression of cyclin E was
      determined by reverse transcription polymerase chain reaction as a further method
      to determine if growth was occurring when the cells were confluent. Alkaline
      phosphatase and von Kossa staining were also performed as a means of determining
      stability in terms of differentiation; that is, are the DFC maintaining their
      phenotype or are they differentiating into osteoblasts and osteocytes? After
      plating cells of a given passage, they initially underwent a rapid phase of
      growth with 30-40% of the cells in S, G(2) and M (dividing track) as determined
      by flow cytometry. The number of such cells declined to only 7-15% at
      preconfluency. At late confluency, only 2 and 5% of the cells were in the
      dividing track in passages 6 and 9, respectively, but in passage 12 this had
      risen to 15%. For a given passage of cells, cyclin E gene expression
      significantly declined in late confluency as compared to the early growth phase.
      However, in passage 12, the gene expression of cyclin E at late confluency was
      higher than the expression at late confluency in passage 6. Thus, the DFC were
      remarkably stable through passage 9, but by passage 12 it appeared that a small
      percentage of the cells had become transformed and had lost their contact
      inhibition growth properties. Alkaline phosphatase and von Kossa staining were
      negative for all passages, suggesting that the cells remained stable in terms of
      differentiation and did not differentiate into either osteoblasts or osteocytes.

PMID- 15144504
TI  - Galvanizing mental health research in low and middle-income countries: role of
      scientific journals.

PMID- 15144502
TI  - Influence of tissue origins and external microenvironment on porcine foetal
      fibroblast growth, proliferative life span and genome stability.
AB  - One of the challenges of manipulating genes in primary cells is that the cells
      have a finite proliferation capacity. This, combined with the lower gene
      targeting efficiency of somatic cells, makes identification of targeted clones
      very difficult. The objective of this study was to establish a system that allows
      porcine foetal fibroblasts to reach their maximal proliferation capacity in
      vitro. The influence of fibroblast origin, stage of foetal development, cell
      seeding densities and concentration of foetal bovine serum (FBS) on the
      population doublings, the percentage of beta-galactosidase-activity-positive
      cells and the genome stability of foetal fibroblasts during in vitro culture was
      investigated. It was found that porcine foetal fibroblasts could be cultured for
      over 80 population doublings in the appropriate culture system. Fibroblasts from
      earlier stages of foetal development were better candidate cells than those from
      the later stages. Cells from the heart were more actively proliferative and more
      resistant to replicative senescence than those from the liver. Compared to 10%
      FBS content, 15% FBS provided better homeostatic support, not only to
      proliferative performance, but also in maintaining a normal karyotype. In
      addition, the proliferative life span of porcine foetal fibroblasts is also
      dependent on seeding density of the culture.

PMID- 15144505
TI  - Australian and New Zealand clinical practice guidelines for the treatment of
      bipolar disorder.
AB  - BACKGROUND: The Royal Australian and New Zealand College of Psychiatrists is co
      ordinating the development of clinical practice guidelines (CPGs) in psychiatry,
      funded under the National Mental Health Strategy (Australia) and the New Zealand
      Health Funding Authority METHOD: For these guidelines, the CPG team reviewed the
      treatment outcome literature (including meta-analyses) and consulted with
      practitioners and consumers. TREATMENT RECOMMENDATIONS: This guideline provides
      evidence-based recommendations for the management of bipolar disorder by phase of
      illness, that is acute mania, mixed episodes and bipolar depression, and the
      prophylaxis of such episodes. It specifies the roles of various mood-stabilizing
      medications and of psychological treatments such as cognitive therapy and psycho
      education.

PMID- 15144506
TI  - Researching psychiatry in Western Australia.
AB  - OBJECTIVE: To provide an overview of the development, approaches and main
      research projects of the Centre for Clinical Research in Neuropsychiatry (CCRN)
      in Perth, Western Australia. METHOD: Discursive. RESULTS: Underlying concepts,
      methods and selected findings of recent research into the neurobiology and
      epidemiology of schizophrenia, autism and other psychotic disorders are
      presented. CONCLUSION: CCRN, one of Australia's youngest centres of psychiatric
      research, has invested fruitfully in research areas such as molecular genetics,
      neuropsychology, neurophysiology, behavioural pharmacology, diagnostic assessment
      procedures and record linkage epidemiology.

PMID- 15144507
TI  - Benign brain tumours and psychiatric morbidity: a 5-years retrospective data
      analysis.
AB  - OBJECTIVE: To examine the psychiatric comorbidity in benign brain tumours.
      METHOD: A retrospective (5 years) data analysis at our 500 bed teaching hospital.
      The diagnoses of benign brain tumours were based on the record of final diagnoses
      in the case records confirmed by either CT or MRI scans. Case records of patients
      with clearly documented history of psychiatric symptoms of several weeks to
      several months duration were identified only if such symptoms had antedated a
      diagnosis of the brain tumour. Using a specially designed proforma, two
      psychiatrists rated the symptoms together. We also collected data on age, gender
      and CT/MRI findings. Consensus was reached on all cases in regard to the
      psychiatric phenomenology. The symptoms were divided according to their
      presentation into purely neurological or psychiatric symptoms. RESULTS: A total
      of 79 patients were identified as having a primary diagnosis of benign brain
      tumour. There were 56 female patients and 23 male patients. Seventy-two of these
      had meningiomas. Fifteen (21%) of 72 meningioma cases, eight men and seven women,
      presented with psychiatric symptoms in the absence of neurological symptoms.
      Affective disorders were a common presentation. There was no correlation between
      brain laterality and the psychiatric comorbidity. CONCLUSIONS: Psychiatric
      symptoms may be the only initial manifestations of meningiomas of the brain in a
      significant number of cases occurring in the fifth decade of life. Such patients
      must be investigated by brain imaging studies even if there are no neurological
      signs or symptoms.

PMID- 15144508
TI  - Psychiatric disorder in women with early stage and advanced breast cancer: a
      comparative analysis.
AB  - OBJECTIVE: To assess psychosocial morbidity in women with breast cancer and to
      compare the differential rates between women with early stage and advanced
      disease. METHOD: In this report, 303 women with early stage breast cancer,
      psychiatrically assessed at baseline (as part of a study of cognitive-existential
      group therapy during adjuvant chemotherapy), are compared with 200 women with
      advanced breast cancer (similarly assessed in a trial of supportive-expressive
      group therapy). A structured psychiatric interview plus self-report measures were
      used to assess psychiatric morbidity, quality of life and cognitive attitude to
      cancer. RESULTS: The early stage patients, whose mean age was 46 years, were on
      average 3 months post-surgery and had an overall prevalence of DSM-IV psychiatric
      diagnosis of 45%. The metastatic patients, whose mean age was 51 years, were on
      average 63 months post-primary diagnosis and had an overall prevalence of DSM-IV
      diagnosis of 42%; the difference between the two rates was not statistically
      significant. Of women with early stage breast cancer, 36.7% had mood disorders,
      9.6% suffering from major depression and 27.1% from minor depression. In the
      metastatic sample 31% had mood disorders, 6.5% having major depression and 24.5%
      with minor depression. Anxiety disorders were present in 8.6% of the early stage
      group and 6% of women with advanced disease. Fatigue, a past history of
      depression, and cognitive attitudes of helplessness, hopelessness or resignation
      were significantly associated with depression in both groups. The women from the
      metastatic sample were significantly less distressed by hair loss but more
      dissatisfied with body image, and had higher rates of lymphoedema and hot flushes
      than the early stage women. CONCLUSIONS: The rates of psychosocial distress are
      high, and similar, across patients with both early and advanced stage breast
      cancer, although the illness related causes of distress are different. These data
      present a challenge to clinical services to provide a comprehensive range of
      support services to ameliorate this distress.

PMID- 15144509
TI  - The trauma of first episode psychosis: the role of cognitive mediation.
AB  - OBJECTIVE: First episode psychosis can be a distressing and traumatic event which
      has been linked to comorbid symptomatology, including anxiety, depression and
      PTSD symptoms (intrusions, avoidance, etc.). However, the link between events
      surrounding a first episode psychosis (i.e. police involvement, admission, use of
      Mental Health Act, etc.) and PTSD symptoms remains unproven. In the PTSD
      literature, attention has now turned to the patient's appraisal of the traumatic
      event as a key mediator. In this study we aim to evaluate the diagnostic status
      of first episode psychosis as a PTSD-triggering event and to determine the extent
      to which cognitive factors such as appraisals and coping mechanisms can mediate
      the expression of PTSD (traumatic) symptomatology. METHOD: Approximately 1.5
      years after their first episode of psychosis, patients were assessed for
      traumatic symptoms, conformity to DSM-IV criteria for posttraumatic stress
      disorder (PTSD), and their appraisals of the traumatic events and coping
      strategies. Psychotic symptomatology was also measured. RESULTS: 31% of the
      sample of 35 patients who agreed to participate reported symptoms consistent with
      a diagnosis of PTSD. Although no relationship was found between PTSD (traumatic)
      symptoms and potentially traumatic aspects of the first episode (including place
      of treatment, detention under the MHA etc.), intrusions and avoidance were
      positively related to retrospective appraisals of stressfulness of the ward (i.e.
      the more stressful they rated it the greater the number of PTSD symptoms) and the
      patient's coping style (sealers were less likely to report intrusive re
      experiencing but more likely to report avoidance). CONCLUSIONS: The results call
      into question whether it is possible to make claims for a simple causal link
      between psychosis and PTSD. Instead patients' appraisals of potentially traumatic
      events and their coping styles may mediate the traumatic impact of a first
      episode of psychosis.

PMID- 15144510
TI  - Self-esteem in patients who have recovered from psychosis: profile and
      relationship to quality of life.
AB  - BACKGROUND: New developments in pharmacotherapy are likely to improve
      substantially the symptomatic recovery from psychosis but low self-esteem may
      compromise quality of life. AIMS: To investigate the profile and correlates of
      self-esteem in individuals who have achieved symptomatic recovery from psychosis
      and determine its relationship with quality of life. METHOD: Sixty-one
      individuals who had been free of psychotic symptoms for 6 months were selected
      during a community-based epidemiological survey of psychoses. Participants were
      evaluated for subjective assessment of self-esteem using a self-report
      questionnaire, for clinical and antecedent features of illness, and for quality
      of life. RESULTS: Forty-three percent had scores in the range indicative of low
      self-esteem on the questionnaire. Level of self-esteem was unrelated to gender,
      employment status, the type of psychotic disorder, course of disorder or
      premorbid social adjustment. Depression was associated with reduced levels of
      self-esteem. However, independent of depression and other confounding variables,
      a low level of self-esteem was a risk factor for impaired quality of life.
      CONCLUSIONS: Self-esteem is often low among persons who have achieved symptomatic
      recovery from psychosis, is associated with depression and is a predictor of
      quality of life.

PMID- 15144511
TI  - Duration of untreated psychosis and treatment outcome in schizophrenia patients
      untreated for many years.
AB  - OBJECTIVE: The duration of untreated psychosis (DUP) influences treatment outcome
      in schizophrenia but its relevance in untreated patients, ill for a very long
      duration, is not known. This study examined outcome and factors related to it
      after one year of treatment of schizophrenia patients who were ill for many years
      and not previously treated. METHOD: Among 75 never-treated patients with
      schizophrenia detected in a community survey in Chennai, India, 49 took treatment
      and were followed up prospectively for one year. Evaluation at intake and outcome
      was carried out using standardized methods. RESULTS: A good clinical outcome in
      29%, social outcome in 35%, occupational outcome in 51% and global outcome in 31%
      was observed at the end of one year. Patients with poor global outcome did not
      significantly differ from those with good outcome on demographic and clinical
      variables at intake but for the presence of delusions and formal thought
      disorder. The proportion with good outcome in clinical, work and global measures
      fell steadily with increasing DUP. This difference was significant for clinical
      and global outcomes after a DUP of 5 years. CONCLUSIONS: The relationship between
      DUP and response to treatment held good even in chronic stages of schizophrenia
      with longer DUP associated with poorer outcome.

PMID- 15144512
TI  - Psychological trauma: psychiatry and the law in conflict.
AB  - OBJECTIVE: To contrast the psychiatric and legal construct of psychological
      trauma, with posttraumatic stress disorder (PTSD) as the reference disorder.
      METHOD: Literature relevant to DSM-IV PTSD definition of a traumatic event
      (Criterion A) was assessed. This construct was compared with the current legal
      status for psychological trauma arising from recent judgements of the Australian
      High Court. CONCLUSIONS: The current legal construct of psychological trauma is
      not only practical and sensible, but is far more evidence-based than the DSM-IV
      construct of trauma.

PMID- 15144513
TI  - The relationship between public causal beliefs and social distance toward
      mentally ill people.
AB  - OBJECTIVE: The aim of this study is to investigate the nature of the relationship
      between public causal beliefs and social distance toward people with mental
      disorders, particularly schizophrenia and depression. METHOD: In total, three
      representative surveys were carried out in Germany, Russia and Mongolia using
      personal, fully structured interviews. RESULTS: Despite the subjects' different
      cultural backgrounds, their responses show similar trends with regard to
      attributing depression and schizophrenia to psychosocial causes: 'acute stress'
      (life event) was most frequently endorsed as the cause for these two disorders.
      The biological causes ('brain disease' and 'heredity') were less frequently
      selected for depression than for schizophrenia. Irrespective of place and type of
      mental disorder, endorsing biological factors as the cause of schizophrenia was
      associated with a greater desire for social distance, the same relationship
      applies to depression in half the instances. CONCLUSIONS: It would be premature
      to draw conclusions with regard to interventions aimed at reducing discrimination
      based on stigma. However, our study provides stimulus for re-considering the
      assumptions underlying antistigma interventions: that promulgating biological
      concepts among the public might not contribute to a desired reduction in social
      distance toward people with mental disorders.

PMID- 15144515
TI  - Quality of life and related risk factors in a Taiwanese Village population 21
      months after an earthquake.
AB  - OBJECTIVE: To investigate quality of life and related risk factors of Taiwanese
      earthquake survivors with different psychiatric disorders 21 months after the
      earthquake. METHOD: This was a population survey. Trained assistants used the
      Medical Outcomes Study Short Form-36 (MOS SF-36) and questionnaires to interview
      461 respondents (209 males and 252 females) 16 years or older who were equally
      exposed to the earthquake. Psychiatrists interviewed the same respondents using
      the Mini-International Neuropsychiatric Interview (MINI), with an adjusted
      response rate of 79.9%. RESULTS: The prevalence of varied psychiatric disorders
      in earthquake survivors ranged from 3.3% to 18%. However, there was almost a
      positive trend in quality of life in survivors among the following groups:
      posttraumatic stress disorder combined with major depressive episode; major
      depressive episode; posttraumatic stress disorder; other psychiatric diseases;
      and healthy mentality groups on the physical aspect or mental aspect of the MOS
      SF-36. When survivors were elderly or female and had experienced prominent
      financial loss immediately after the earthquake, social network change, and
      mental impairment, their quality of life tended to be worse. CONCLUSION: The
      earthquake survivors had a higher percentage of psychiatric disorders. The risk
      factors that affected quality of life in survivors were age, female sex,
      financial loss, social network change, and mental impairment.

PMID- 15144516
TI  - Early risk factors for adolescent antisocial behaviour: an Australian
      longitudinal study.
AB  - OBJECTIVE: This investigation utilizes data from an Australian longitudinal study
      to identify early risk factors for adolescent antisocial behaviour. METHOD:
      Analyses are based on data from the Mater University Study of Pregnancy, an on
      going longitudinal investigation of women's and children's health and development
      involving over 8000 participants. Five types of risk factors (child
      characteristics, perinatal factors, maternal/familial characteristics, maternal
      pre- and post-natal substance use and parenting practices) were included in
      analyses and were based on maternal reports, child assessments and medical
      records. Adolescent antisocial behaviour was measured when children were 14 years
      old, using the delinquency subscale of the Child Behaviour Checklist. RESULTS:
      Based on a series of logistic regression models, significant risk factors for
      adolescent antisocial behaviour included children's prior problem behaviour (i.e.
      aggression and attention/restlessness problems at age 5 years) and marital
      instability, which doubled or tripled the odds of antisocial behaviour. Perinatal
      factors, maternal substance use, and parenting practices were relatively poor
      predictors of antisocial behaviour. CONCLUSIONS: Few studies have assessed early
      predictors of antisocial behaviour in Australia and the current results can be
      used to inform prevention programs that target risk factors likely to lead to
      problem outcomes for Australian youth.

PMID- 15144517
TI  - Prevention and treatment of childhood and adolescent aggression and antisocial
      behaviour: a selective review.
AB  - OBJECTIVE: In this paper I examine the possible role of public sector child and
      youth mental health services in prevention and treatment of childhood and
      adolescent aggression. The problem of juvenile antisocial behaviour in Australian
      society is discussed. METHOD: The review details the extent, concern and costs of
      juvenile antisocial behaviour. The most efficacious prevention and treatment
      programs for aggressive and antisocial behaviour are reviewed within the context
      of reforms to public sector mental health services. The place of evidence-based
      mental health programs within child and youth mental health services is
      discussed. RESULTS: Recommendations are made on the adoption of selective
      programs demonstrated to be efficacious in the prevention and treatment of
      aggression and antisocial behaviour. CONCLUSION: Child and youth mental health
      services can make a specific contribution to crime prevention.

PMID- 15144518
TI  - Irreversible priapism during olanzapine and lithium therapy.

PMID- 15144519
TI  - Recurrent seasonal confusional psychosis: a diagnostic dilemma.

PMID- 15144520
TI  - Fluoxetine-induced breast atrophy.

PMID- 15144526
TI  - Removal of small non-enveloped viruses by nanofiltration.
AB  - BACKGROUND AND OBJECTIVES: Nanofiltration is one of the most effective virus
      reduction methods in the manufacturing process of plasma products. However, it is
      difficult to remove small viruses from high molecular weight protein preparations
      like immunoglobulin G or factor VIII complex by nanofiltration, because the size
      of the protein is similar to that of viruses. In order to separate the viruses
      from these proteins by nanofiltration, it is necessary to change the size of
      either one. In this study, we report that such non-enveloped viruses as human
      parvovirus B19 (B19), human encephalomyocarditis virus (EMC) or porcine
      parvovirus (PPV) aggregate in the presence of certain kinds of amino acids and
      could be easily removed by nanofiltration. MATERIALS AND METHODS: 0.3 M Glycine
      (or other amino acid) solution spiked with viruses was subjected to dead-end
      single filtration with a 35-nm pore-size filter. Virus removal by nanofiltration
      was either evaluated by PCR or by infectivity assay. RESULTS: B19 in a 0.3 M
      glycine solution was reduced to 1:10(7.5) (7.5-log) by nanofiltration with a 35
      nm pore-sized filter, whereas in PBS it was not reduced. Similarly, B19 was also
      reduced when suspended in other amino acids solutions. This effect was also
      confirmed with the other small non-enveloped viruses EMC or PPV. When 5% globulin
      or 5% albumin was added to a 0.3 M glycine solution, the removal rate was
      decreased. CONCLUSIONS: These data suggest that viruses in the presence of
      certain kinds of amino acids could be aggregated and effectively removed by a
      filter that has a pore size larger than the size of the viruses.

PMID- 15144528
TI  - Implementation of the INTERCEPT Blood System for Platelets into routine blood
      bank manufacturing procedures: evaluation of apheresis platelets.
AB  - BACKGROUND AND OBJECTIVES: The INTERCEPT Blood System for Platelets utilizes
      amotosalen-HCl (S-59) in combination with ultraviolet A (UVA) light to inactivate
      viruses, bacteria, protozoa and leucocytes that may contaminate platelet
      concentrates (PCs). To facilitate implementation of this technique into routine
      blood bank manufacturing procedures, this study evaluated the impact of different
      time settings of photochemical treatment on in vitro platelet function. MATERIALS
      AND METHODS: Platelets derived from apheresis (6.5-7.0 x 10(11) platelets) were
      resuspended in 240 ml of autologous plasma and 360 ml of platelet additive
      solution (PAS III) and split into two equal-sized PC units. Whereas one unit was
      not treated, the other was treated with 150 microm amotosalen and 3 J/cm2 UVA
      light followed by a compound adsorption device (CAD) step for reduction of
      residual amotosalen and photoproducts. In a first series of experiments (arm A, n
      = 7), PC units were photochemically treated after an overnight storage period of
      16-23 h followed by a CAD step of 4 h. In a second series (arm B, n = 8),
      photochemical treatment occurred after a short storage time of 4 h with a
      subsequent CAD step of 16 h. Platelet function was evaluated by assaying blood
      gas analysis, glucose and lactate concentration, lactate dehydrogenase (LDH),
      hypotonic shock response (HSR) and the expression of CD62p, over a period of 7
      days. RESULTS: Neither of the photochemical treatment procedures showed
      differences for pH, pCO2, pO2, HCO3, glucose consumption or platelet activation
      until the end of day 7. Increased lactate values detected for the treated units
      of arm A at the end of the storage period were independent from the PCT time
      setting. CONCLUSIONS: Photochemical pathogen inactivation with different initial
      resting periods between 4 and 23 h, and different CAD steps of 4 and 16 h, had no
      influence on the platelet in vitro function during 7 days of storage.

PMID- 15144527
TI  - Virus inactivation and protein recovery in a novel ultraviolet-C reactor.
AB  - BACKGROUND AND OBJECTIVES: Ultraviolet-C (UVC) irradiation is a viral
      inactivation method that was dismissed by many plasma fractionators as a result
      of the potential for protein damage and the difficulty in delivering uniform
      doses. A reactor with novel spiral flow hydraulic mixing was recently designed
      for uniform and controlled UVC treatment. The objective of this study was to
      investigate virus inactivation and protein recovery after treatment through the
      new reactor. MATERIALS AND METHODS: Virus- and mock-spiked Alpha1-proteinase
      inhibitor (Alpha1-PI) solutions were treated with UVC. The virus samples were
      assayed for residual infectivity and amplified by the polymerase chain reaction
      (PCR). The mock-spiked samples were assayed for protein integrity. RESULTS:
      Greater than 4 log10 of all test viruses were inactivated, regardless of the type
      of nucleic acid or presence of an envelope. Unlike previous studies, viruses with
      the smallest genomes were found to be those most sensitive to UVC irradiation,
      and detection of PCR amplicons > or = 2.0 kb was correlated to viral infectivity.
      Doses that achieved significant virus inactivation yielded recovery of > 90%
      protein activity, even in the absence of quenchers. CONCLUSIONS: The results
      demonstrate the effectiveness of UVC treatment, in the novel reactor, to
      inactivate viruses without causing significant protein damage, and confirm the
      utility of large PCR amplicons as markers for infectious virus.

PMID- 15144529
TI  - Methylene blue-photoinactivated plasma vs. fresh-frozen plasma as replacement
      fluid for plasma exchange in thrombotic thrombocytopenic purpura.
AB  - BACKGROUND AND OBJECTIVES: Plasma exchange with fresh-frozen plasma (FFP) is the
      treatment of choice in thrombotic thrombocytopenic purpura (TTP). Methylene blue
      photoinactivated plasma (MBPIP) has been proposed as a safer alternative to FFP,
      but its effectiveness in the treatment of TTP is not well established. The
      purpose of this study was to investigate whether MBPIP is as effective as FFP in
      the treatment of TTP by plasma exchange. MATERIALS AND METHODS: A retrospective
      analysis was carried out of 56 TTP episodes, occurring between 1990 and 2003,
      which had been treated by plasma exchange. MBPIP was used for fluid replacement
      in 27 episodes and FFP in 29. The effect of plasma (MBPIP or FFP) on treatment
      outcomes was analysed by multivariate logistic regression. RESULTS: Compared to
      patients treated with FFP, those receiving MBPIP had an increased risk of dying
      from progressive TTP [adjusted odds ratio (OR) = 31; 95% confidence interval
      (CI): 1.2 to > 100], a greater number of recurrences while on plasma exchange
      therapy (OR = 4.6; 95% CI: 1.2-17), and a lower probability of attaining a
      sustained remission within 9 days of starting plasma exchange (OR = 5.2; 95% CI:
      1.3-20). CONCLUSIONS: MBPIP seems to be less effective than FFP in the treatment
      of TTP. It is therefore prudent to avoid MBPIP until therapeutic equivalency to
      FFP has been established by randomized, controlled trials.

PMID- 15144530
TI  - Impact of tobacco smoking on platelet function in apheresis products in vitro.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the platelet
      function, over a 5-day time-period, of apheresis-derived platelet concentrates
      obtained from smokers and non-smokers. MATERIALS AND METHODS: Smoker and non
      smoker plateletpheresis products were investigated on days 1, 3 and 5 of storage.
      Receptor expression (as evaluated by flow cytometry) and the platelet aggregation
      response were measured. RESULTS: There was only a slight loss of platelet
      function in apheresis products from smokers compared to non-smokers. CONCLUSIONS:
      Smoking does not significantly change the quality of platelet preparations. The
      current practice, of not to exclude smokers from platelet donation, can be
      continued.

PMID- 15144531
TI  - Fibrin sealant produced by the CryoSeal FS System: product chemistry, material
      properties and possible preparation in the autologous preoperative setting.
AB  - BACKGROUND AND OBJECTIVES: The CryoSeal FS has been introduced as an automated
      device for the production of fibrin sealant from small volumes of plasma. We
      tested this device and compared the product with commercially available fibrin
      sealants and with the requirements of the European Pharmacopoeia. MATERIALS AND
      METHODS: The CP3 program and disposables required were used to manufacture fibrin
      sealant. The chemistry and mechanical properties of the product were
      investigated. RESULTS: The cryoprecipitate generated with CryoSeal contains
      concentrated fibrinogen and critical clotting factors. The efficiency of the
      production process is poor, but the production procedure itself is simple and not
      time-consuming. The volume of plasma required allows application in the
      preoperative autologous setting. CONCLUSIONS: The CryoSeal FS is an automated
      device for cryoprecipitation and production of thrombin. It can be implemented
      easily in the clinical routine, although, owing to product specifications, the
      efficacy of the CryoSeal fibrin sealant requires further clinical trials.

PMID- 15144532
TI  - Rhabdomyolysis in allogeneic peripheral blood stem cell donors.

PMID- 15144533
TI  - Prolonged hepatitis C virus seroconversion in a blood donor, detected by HCV
      antigen test in parallel with HCV RNA.

PMID- 15144534
TI  - "Serious hazards of transfusion" underestimates the incidence of transfusion
      related acute lung injury in the UK.

PMID- 15144537
TI  - Institutionalized racism and end-stage renal disease: is its impact real or
      illusionary?
AB  - Racism is the subjugation of one group (superior) over another (inferior) and may
      be divided into two categories: overt (gross) and covert. Covert racism
      (subconscious) is categorized as institutionalized racism. Although
      institutionalized racism is a more tolerant and restrained practice of this
      superior/inferior ethnic construct in which African Americans or other people of
      color are treated as inferiors, it has led to important health disparities
      between blacks and whites. One area where its mark is most indelible is in the
      treatment of end-stage renal disease (ESRD).

PMID- 15144538
TI  - Improved survival with higher hematocrits: where is the evidence?
AB  - The Centers for Medicare and Medicaid Services (CMS) is reviewing Medicare
      coverage policy for recombinant human erythropoietin (epoetin) therapy. CMS
      officials are concerned that "Medicare spending on EPO may be higher than
      necessary without resulting in optimal patient benefit." Approximately 190 end
      stage renal disease (ESRD) patients die each day-a mortality rate that has
      remained essentially unchanged since 1994-despite improvements in the "adequacy
      of dialysis, vascular access, and anemia management". To date, the evidence cited
      in support of a survival benefit of epoetin confuses the relationship between
      treatment response and outcomes with a causal effect of epoetin. A variety of
      mechanisms may account for a non-causal association between hematocrit and
      mortality can occur. We conclude that there is no basis for inferring the
      survival benefits (or detriments) of increasing a patient's hematocrit by
      adjusting the dosing of epoetin. Furthermore, we note that caution is required in
      administering large doses of epoetin to unresponsive patients in order to achieve
      the target hematocrit. A better understanding of the epoetin/survival
      relationship, well-grounded in science, is needed to provide a basis for CMS to
      improve its current epoetin policies, and may help to improve patient mortality.

PMID- 15144539
TI  - Cardiac arrest in dialysis patients: taking a small step.
AB  - Dialysis patients are at high risk for death, and cardiac disease accounts for
      43% of all-cause mortality. The single greatest cause of death in dialysis
      patients is sudden cardiac death. The survival of dialysis patients after cardiac
      arrest is poor. Clinical strategies for improving the outcomes of dialysis
      patients should include therapies to reduce the risk of cardiac arrest and the
      likelihood of surviving cardiac arrest. Defibrillators should be available in all
      dialysis centers.

PMID- 15144540
TI  - How can the poor outcomes for diabetic dialysis patients be improved?

PMID- 15144542
TI  - How can the poor outcomes for diabetic dialysis patients be improved?

PMID- 15144541
TI  - How can the poor outcomes for diabetic dialysis patients be improved?

PMID- 15144543
TI  - How can the poor outcomes for diabetic dialysis patients be improved?

PMID- 15144544
TI  - How can the poor outcomes for diabetic dialysis patients be improved?

PMID- 15144545
TI  - Residual renal function: considerations on its importance and preservation in
      dialysis patients.
AB  - Residual renal function (RRF) remains important even after commencement of
      dialysis. Its role in the adequacy of peritoneal dialysis (PD) is well recognized
      and is increasingly utilized in incremental PD regimes, but it is also vitally
      important in hemodialysis (HD) patients, in whom it, as in PD patients, may
      improve survival. It may allow for a reduction in the duration of HD sessions. It
      reduces the need for dietary and fluid restrictions in both PD and HD patients.
      Other contributions include improved middle molecule clearance, better
      hemoglobin, phosphate, potassium, and urate levels, enhanced nutritional status
      and quality of life scores, and better outcomes in pregnancy. On the negative
      side, hypoalbuminemia may be prolonged in patients with persistent nephrotic
      range proteinuria. Contrary to popular belief, RRF does not necessarily decline
      rapidly with the initiation of HD. PD may be better than HD in preserving RRF,
      although this difference may not persist if biocompatible membranes, bicarbonate
      buffer, and ultrapure water are used. Nocturnal ambulatory peritoneal dialysis
      (APD) patients may fare worse than continuous ambulatory peritoneal dialysis
      (CAPD) patients. RRF can be adversely affected by angiotensin-converting enzyme
      (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides,
      and radiocontrast agents. Diuretics can help maintain fluid balance but not RRF.

PMID- 15144546
TI  - Testosterone metabolism and replacement therapy in patients with end-stage renal
      disease.
AB  - Hypogonadism is common among men with end-stage renal disease (ESRD), beginning
      before the need for dialysis and not improved with the initiation of dialysis.
      Many of the manifestations of hypogonadism, such as bone disease and muscle
      wasting, are also frequently seen among dialysis patients. There have been few
      studies of testosterone replacement therapy in this patient population, but
      available data suggest that testosterone can be administered without adjustment
      of the doses used in hypogonadal men with normal renal function. Extrapolation
      from results of treatment of hypogonadal older men with normal renal function
      suggests that testosterone replacement could improve libido and could have
      salutary effects on muscle mass and bone mineral density in patients with kidney
      disease. However, caution is warranted because of the potential side effects of
      testosterone therapy, and further research is needed to more precisely define the
      balance of risk and benefit in patients with chronic kidney disease. Specifically
      it will be important to determine the prevalence and clinical significance of
      hypogonadism in ESRD patients in the modern era and to measure the effects of
      replacement therapy on various symptoms of hypogonadism as well as on overall
      quality of life, physical functioning, and survival.

PMID- 15144547
TI  - The consequences of uncontrolled secondary hyperparathyroidism and its treatment
      in chronic kidney disease.
AB  - Secondary hyperparathyroidism (HPT) is a common complication of chronic kidney
      disease (CKD) and a frequent cause of clinically significant bone disease. Soft
      tissue and vascular calcification, cardiovascular disease, and calcific uremic
      arteriolopathy (CUA) are additional serious consequences of the disorder that may
      contribute directly to cardiovascular morbidity and mortality in patients with
      CKD. Less widely appreciated manifestations include neurological disturbances,
      hematological abnormalities, and endocrine dysfunction. Secondary HPT arises from
      alterations in calcium, phosphorus, and vitamin D metabolism that develop early
      in the course of CKD and become more pronounced as kidney function declines.
      Treatment is often delayed, however, until the disease is well established.
      Current therapeutic strategies rely largely on the use of vitamin D sterols to
      diminish excess parathyroid hormone (PTH) synthesis and to lower serum or plasma
      PTH levels, but their use is often confounded by increases in serum calcium and
      phosphorus concentrations, changes that can aggravate soft-tissue and vascular
      calcification. As such, there is a need for new therapeutic interventions that
      can effectively lower serum or plasma PTH levels without producing untoward side
      effects. The current review summarizes the diverse manifestations of secondary
      HPT in patients with CKD. The consequences of inadequately controlled secondary
      HPT and the adverse effects of selected therapeutic interventions for the
      disorder on vascular calcification and cardiovascular disease in those with CKD
      are discussed.

PMID- 15144548
TI  - Evidence-based data for the hemodialysis access surgeon.
AB  - The National Kidney Foundation Dialysis Outcomes Quality Initiative Clinical
      Practice Guidelines for Vascular Access (DOQI) have defined the access-related
      care for patients with end-stage renal disease (ESRD). However, the standard of
      care across the country has fallen short of the DOQI targets. One potential
      explanation for these shortcomings is the lack of compelling evidence in the
      literature to support the recommendations. This study was designed to compare the
      DOQI with the best available evidence in the literature for four clinical
      questions relevant to the hemodialysis access surgeon: the choice of access type
      (autogenous versus prosthetic), the type of prosthetic graft, management of the
      "failing" (nonthrombosed) access, and management of the thrombosed access. The
      electronic literature databases MEDLINE and Evidence-Based Medicine Reviews were
      searched and relevant randomized controlled trials or meta-analyses were
      identified for review. No randomized controlled trials comparing autogenous to
      prosthetic accesses were identified. However, a recent systematic review reported
      that the patency rates for upper extremity autogenous accesses were superior to
      their polytetrafluoroethylene (PTFE) counterparts. The identified randomized
      trials suggested that the patency rates for the different types of commercially
      available prosthetic grafts used for access appear comparable. They suggested
      that standard wall PTFE thickness and prosthetic anastomotic cuffs may be
      associated with better graft patency, while venous cuffs may be associated with
      worse patency. Furthermore, the trials suggested percutaneous angioplasty of
      "failing" prosthetic accesses with greater than 50% stenoses did not appear to
      improve patency and that routine use of intraluminal stents, as an adjunct to
      angioplasty, was not beneficial. They did suggest that patency after open
      surgical revision of "failing" prosthetic accesses was superior to that after
      percutaneous angioplasty. Lastly, the identified trials suggested that the
      patency rates after open surgical revision of thrombosed prosthetic accesses was
      better than after endovascular treatment. Despite the magnitude of hemodialysis
      related access problems, the quality of the evidence supporting the clinical
      decisions relevant to the access surgeon is limited and further clinical trials
      are justified.

PMID- 15144549
TI  - Nitric oxide and hemodialysis.
AB  - Nitric oxide (NO), previously thought of as a noxious gas, is now recognized as
      an important mediator of vascular responsiveness. Soon after its discovery, it
      was realized that the actions of NO are similar to the previously described
      endothelium-derived relaxing factor (EDRF). It is synthesized in the vascular
      endothelium utilizing the enzyme nitric oxide synthase (NOS) and diffuses in the
      adjacent vascular media, where it has a vasodilatory action. Opposing actions of
      NO and vasoconstrictor agents (such as endothelin-1, angiotensin IotaIota, and
      others) maintain the vascular tone of the renal arteries. The same balance at the
      level of the macula densa maintains glomerular filtration rate (GFR) during
      varying levels of salt excretion. Lack of NO can result in disruption of this
      fine balance, with resultant vasoconstriction and disease progression,
      hypertension, and accelerated atherosclerosis. In addition, hypertension may
      result from positive salt balance that occurs when macula densa NOS is inhibited.
      While most investigators report low levels of NO in uremic subjects, the levels
      in hemodialysis (HD) patients have not been characterized adequately. This is
      primarily because HD patients are exposed to both stimulatory and inhibitory
      factors for NO synthesis. Retention of inhibitors of NOS tends to decrease NO
      levels, whereas production of NO will be increased by cytokines generated during
      blood-dialyzer interaction. There is less disagreement, however, over the finding
      of elevated levels in those with dialyzer reactions and dialysis-induced
      hypotension. Recent developments in the isolation of inducible and constitutive
      forms of NOS makes understanding of its pathophysiologic effects more complete.
      Newer treatment directed at inhibiting only the inducible forms of NOS (sparing
      the constitutive forms) may soon be found useful for the treatment and prevention
      of hypotension and dialyzer reactions in HD patients.

PMID- 15144550
TI  - The body mass index paradox and an obesity, inflammation, and atherosclerosis
      syndrome in chronic kidney disease.
AB  - The association of high body mass index (BMI) with better survival in chronic
      kidney disease (CKD) is considered a "risk factor paradox" or "reverse
      epidemiology." Since malnutrition is a powerful predictor of death and
      cardiovascular disease is its leading cause, it has been suggested that
      malnutrition and atherosclerosis must be associated. Thus the current paradigm is
      that malnutrition is a risk factor for atherosclerosis and obesity is protective
      in CKD patients. We recently showed that high-BMI patients with inferred high
      body fat have an increased prevalence of atherosclerosis and subsequent
      cardiovascular and all-cause mortality. Prior cross-sectional studies also showed
      that high BMI in CKD is associated with higher C-reactive protein (CRP) levels
      and increased coronary calcification on electron beam computed tomography (CT)
      scan. These apparently conflicting data on better survival but increased
      inflammation and atherosclerosis in high-BMI CKD patients could be explained as
      follows. It is hypothesized that nutrition exerts a much stronger influence on
      survival than atherosclerosis in CKD. Malnutrition strongly augments the hazard
      of death from coexistent diseases, while better nutrition has the opposite
      effect. Thus the risk of death is highest in malnourished patients (low muscle
      and low fat mass) and lowest in well-nourished patients (high BMI, high muscle
      mass). Obesity (high BMI, high fat mass) is associated with inflammation and
      atherosclerosis. The risk of death from obesity and atherosclerosis is increased,
      but not so much as occurs with malnutrition. Therefore high body fat patients
      have intermediate survival. Thus it is postulated that an association of obesity,
      inflammation, and atherosclerosis (OIA syndrome) might exist in CKD.

PMID- 15144551
TI  - Interventionalist's role in identifying candidates for secondary fistulas.
AB  - One hundred consecutive patients with upper extremity prosthetic grafts referred
      for either an angioplasty or treatment of a thrombosed graft were included in the
      study. After the patient's treatment was concluded, the angiographic images that
      had been created during the case were evaluated to determine if an upper arm vein
      was evident that would be suitable for the construction of an arteriovenous
      fistula (AVF). Criteria used to determine suitability included vein size measured
      at the level of the elbow, feeding artery size at the level of the elbow, absence
      of stenosis within the vein, and continuity with downstream unobstructed veins.
      Thirty-eight percent of patients had an upper arm graft and 62% had a lower arm
      graft. Since it was not possible to adequately evaluate patients with an upper
      arm graft, these patients were not included in any further evaluations. A total
      of 46 patients (74%) with a forearm loop graft had one or both of the upper arm
      veins that appeared to be optimum for the creation of an AVF. If the percentage
      of graft patients with venous anatomy conducive to the creation of a fistula
      revealed in this study is representative, then the percentage of fistulas in use
      could be very quickly increased to more than 50% by simply seizing the
      opportunity. This effort directed toward prevalent patients could yield results
      much more rapidly than limiting one's focus to incident patients.

PMID- 15144552
TI  - Depression: a common but underrecognized condition associated with end-stage
      renal disease.
AB  - We describe a patient with end-stage renal disease (ESRD) who developed
      depression over the period of dialysis initiation. Depression is an extremely
      common but underrecognized disorder in the dialysis population, which is one of
      the rationales for this case report. Here we present the epidemiology, mechanisms
      for diagnosis, associations with medical morbidity, and treatment modalities
      specifically for patients on dialysis.

PMID- 15144554
TI  - Dysfunction of new catheters by old fibrin sheaths.

PMID- 15144555
TI  - Arteriovenous fistula stenosis: new terminology.

PMID- 15144558
TI  - Decentralization's impact on the health workforce: Perspectives of managers,
      workers and national leaders.
AB  - Designers and implementers of decentralization and other reform measures have
      focused much attention on financial and structural reform measures, but ignored
      their human resource implications. Concern is mounting about the impact that the
      reallocation of roles and responsibilities has had on the health workforce and
      its management, but the experiences and lessons of different countries have not
      been widely shared. This paper examines evidence from published literature on
      decentralization's impact on the demand side of the human resource equation, as
      well as the factors that have contributed to the impact. The elements that make
      such an impact analysis exceptionally complex are identified. They include the
      mode of decentralization that a country is implementing, the level of
      responsibility for the salary budget and pay determination, and the civil service
      status of transferred health workers.The main body of the paper is devoted to
      examining decentralization's impact on human resource issues from three different
      perspectives: that of local health managers, health workers themselves, and
      national health leaders. These three groups have different concerns in the human
      resource realm, and consequently, have been differently affected by
      decentralization processes. The paper concludes with recommendations regarding
      three key concerns that national authorities and international agencies should
      give prompt attention to. They are (1) defining the essential human resource
      policy, planning and management skills for national human resource managers who
      work in decentralized countries, and developing training programs to equip them
      with such skills; (2) supporting research that focuses on improving the knowledge
      base of how different modes of decentralization impact on staffing equity; and
      (3) identifying factors that most critically influence health worker motivation
      and performance under decentralization, and documenting the most cost-effective
      best practices to improve them. Notable experiences from South Africa, Ghana,
      Indonesia and Mexico are shared in an annex.

PMID- 15144559
TI  - MRI of coronary artery atherosclerosis in rabbits: Histopathology-MRI correlation
      and atheroma characterization.
AB  - BACKGROUND AND OBJECTIVES: We report in vivo magnetic resonance imaging (MRI)
      characteristics and histopathology correlation of the thrombus formation in
      atherosclerosis the rabbit animal model. DESIGN AND METHODS: Atherosclerosis was
      induced in white male rabbits with vegetable ghee followed oxidized diet.
      Baseline MRI of atherosclerosis-recruited rabbits was done and later animals were
      used for atheroma histopathology characterization. Contiguous cross-sectional T2
      weighted fast spin echo MRI images were compared by coronary histopathology. In
      all animals, coronary aortic wall thickening and atheroma size was measured using
      MRI. RESULTS: MRI images and digitized histological sections confirmed
      intraluminal thrombus in 6 (67%) of the 9 animals. MRI data showed correlation
      with the histopathology for aortic wall thickness (R2 = 0.82, P < 0.0001), lumen
      area (R2 = 0.88, P < 0.0001) and plaque size (R2 = 0.77, P < 0.0001). Optimized
      TE and TR parameters and multicontrast enhancement generated better MRI
      visibility of vulnerable plaque components. The MRI data evaluated % stenosis,
      plaque burden. Frequency of plaques, plaque height in aorta and coronary artery
      atheroma was also assessed by histology. In vivo, MRI determined the presence and
      size of the thrombus in this animal model of atherosclerosis and histopathology
      defined the plaque disruption. CONCLUSION: The combination of in vivo MRI and
      comparison with histopathology images of rabbit coronary thrombus may be a
      research tool for understanding of the pathogenesis of acute coronary plaques.

PMID- 15144560
TI  - Association of the T allele of an intronic single nucleotide polymorphism in the
      colony stimulating factor 1 receptor with Crohn's disease: a case-control study.
AB  - BACKGROUND: Polymorphisms in several genes (NOD2, MDR1, SLC22A4) have been
      associated with susceptibility to Crohn's disease. Identification of the
      remaining Crohn's susceptibility genes is essential for the development of
      disease-specific targets for immunotherapy. Using gene expression analysis, we
      identified a differentially expressed gene on 5q33, the colony stimulating factor
      1 receptor (CSF1R) gene, and hypothesized that it is a Crohn's susceptibility
      gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in
      innate immunity. METHODS: Patients provided informed consent prior to entry into
      the study as approved by the Institutional Review Board at LSU Health Sciences
      Center. We performed forward and reverse sequencing of genomic DNA from 111
      unrelated patients with Crohn's disease and 108 controls. We also stained
      paraffin-embedded, ileal and colonic tissue sections from patients with Crohn's
      disease and controls with a polyclonal antibody raised against the human CSF1R
      protein. RESULTS: A single nucleotide polymorphism (A2033T) near a Runx1 binding
      site in the eleventh intron of the colony stimulating factor 1 receptor was
      identified. The T allele of this single nucleotide polymorphism occurred in 27%
      of patients with Crohn's disease but in only 13% of controls (X2 = 6.74, p <
      0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry,
      positive staining with a polyclonal antibody to CSF1R was observed in the
      superficial epithelium of ileal and colonic tissue sections. CONCLUSIONS: We
      conclude that the colony stimulating factor receptor 1 gene may be a
      susceptibility gene for Crohn's disease.

PMID- 15144563
TI  - Keeping up with protein folding.

PMID- 15144562
TI  - Short and long term treatment of asthma with intravenous nutrients.
AB  - BACKGROUND: Asthma is an increasing problem in this country and others. Although
      medications for the treatment of asthma abound and are improving, there are
      inherent risks and side effects with all of them. Intravenous magnesium has been
      employed in the treatment of acute asthma, but its use has not become universal,
      nor has it been studied for the treatment of chronic asthma. It is known to be a
      safe drug with minimal side effects. In this study, the author investigates the
      use of magnesium and other nutrients in the treatment of both acute and chronic
      asthma. METHODS: In this non-blinded outcome study, following informed consent,
      forty-three (43) randomly selected volunteer patients with both acute and chronic
      asthma were treated with IV infusions described herein. All patients were
      observed with spirometry 10 minutes post-infusion; two sub-groups of patients
      were also observed after multiple infusions over a short period of time (less
      than one month) and a longer period of time (average 5.8 months). Pulmonary
      function was analyzed by spirometric testing with pre- and post-infusion
      spirometric measurements with the pre/post group. For longer term (Trend)
      patients, baseline spirometry measurements were compared to spirometry
      measurements after patients had received multiple infusions over a period of
      time. Eight (8) patients were measured for both pre/post and Trend data. RESULTS:
      The 38 pre-infusion/post-infusion patients with acute and chronic asthma
      demonstrated an overall average improvement (percentage improvement in percent
      predicted) of 45%. The 13 patients measured for improvement over time (Trend
      data, average duration 5.82 months), demonstrated an overall average improvement
      (percentage improvement in percent predicted) of 57%. Of the 13 patients in the
      multiple infusion group, 9 patients who received longer-term therapy (average
      duration of 12.58 months) for chronic asthma demonstrated an overall average
      improvement of 95% (percentage improvement in percent predicted). CONCLUSION: The
      use of intravenous treatment with multiple nutrients, including magnesium, for
      acute and chronic asthma may be of considerable benefit. Pulmonary function
      improved progressively the longer patients received treatment.

PMID- 15144561
TI  - Eosinophilia in a patient with cyclical vomiting: a case report.
AB  - BACKGROUND: Eosinophilic gastritis is related to eosinophilic gastroenteritis,
      varying only in regards to the extent of disease and small bowel involvement.
      Common symptoms reported are similar to our patient's including: abdominal pain,
      epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema,
      dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of
      eosinophilic infiltration usually occur in the lamina propria or submucosa with
      perivascular aggregates. The disease is likely mediated by eosinophils activated
      by various cytokines and chemokines. Therapy centers around the use of
      immunosuppressive agents and dietary therapy if food allergy is a factor. CASE
      PRESENTATION: The patient is a 31 year old Caucasian female with a past medical
      history significant for ulcerative colitis. She presented with recurrent bouts of
      vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of
      vomiting had been reoccurring every 7-10 days, with each episode lasting for 1-3
      days. This was associated with extreme weakness and cachexia. Gastric biopsies
      revealed intense eosinophilic infiltration. The patient responded to
      glucocorticoids and azathioprine. The differential diagnosis and molecular
      pathogenesis of eosinophilic gastritis as well as the molecular effects of
      glucocorticoids in eosinophilic disorders are discussed. CONCLUSIONS: The patient
      responded to a combination of glucocorticosteroids and azathioprine with
      decreased eosinophilia and symptoms. It is likely that eosinophil-active
      cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating
      factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as
      eotaxin may be involved in eosinophil recruitment. These mediators are
      downregulated or inhibited by the use of immunosuppressive medications.

PMID- 15144567
TI  - Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.
AB  - Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with
      tuberculosis (TB) pleural effusion. Recent studies from the west have found that
      estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy
      for these patients. The diagnostic utility of pleural effusion IFN-gamma level
      estimation has not been evaluated in patients from developing countries, however.
      This work was carried out to study the diagnostic utility of IFN-gamma level
      estimation in patients with TB pleural effusion and to define the best cutoff of
      IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural
      effusion. Of these, 64 were found to have a TB etiology, established by means of
      various conventional modalities. Measurement of pleural fluid IFN-gamma levels
      was done by ELISA technique. The median value of pleural fluid IFN-gamma levels
      in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher
      (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The
      receiver operator characteristic (ROC) curve for IFN-gamma showed an area under
      the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml.
      Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB,
      sensitivity, specificity, negative predictive value, and positive predictive
      value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation
      of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB
      pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and
      specificity for diagnosis of TB.

PMID- 15144564
TI  - Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation
      of HEF1.
AB  - BACKGROUND: The Transforming Growth Factor-beta (TGF-beta) regulates myriad
      cellular events by signaling through members of the Smad family signal
      transducers. As a key signal transducer of TGF-beta, Smad3 exhibits the property
      of receptor-activated transcriptional modulator and also the novel ability of
      regulating the proteasomal degradation of two Smad3 interacting proteins, SnoN
      and HEF1. It has been shown that Smad3 recruits two types of Ub E3 ligases,
      Smurf2 and the Anaphase Promoting Complex (APC), to mediate SnoN ubiquitination,
      thereby enhancing SnoN degradation. The molecular mechanisms underlying Smad3
      regulated HEF1 degradation are not well understood. Furthermore, it is not clear
      how Smad3 recruits the APC complex. RESULTS: We detected physical interaction
      between Smad3 and an APC component APC10, as well as the interaction between HEF1
      and CDH1, which is the substrate-interacting component within APC. Detailed
      domain mapping studies revealed distinct subdomains within the MH2 domain of
      Smad3 for binding to APC10 and HEF1 and suggests the formation of a complex of
      these four proteins (Smad3, HEF1, APC10 and CDH1). In addition, the protein
      levels of HEF1 are subjected to the regulation of overexpressed APC10 and CDH1.
      CONCLUSIONS: Our data suggests that Smad3 may recruit the APC complex via a
      direct interaction with the APC subunit APC10 to regulate the ubiquitination and
      degradation of its interactor HEF1, which is recognized as an ubiquitination
      substrate by the CDH1 subunit of the APC complex.

PMID- 15144565
TI  - Gene finding in novel genomes.
AB  - BACKGROUND: Computational gene prediction continues to be an important problem,
      especially for genomes with little experimental data. RESULTS: I introduce the
      SNAP gene finder which has been designed to be easily adaptable to a variety of
      genomes. In novel genomes without an appropriate gene finder, I demonstrate that
      employing a foreign gene finder can produce highly inaccurate results, and that
      the most compatible parameters may not come from the nearest phylogenetic
      neighbor. I find that foreign gene finders are more usefully employed to
      bootstrap parameter estimation and that the resulting parameters can be highly
      accurate. CONCLUSION: Since gene prediction is sensitive to species-specific
      parameters, every genome needs a dedicated gene finder.

PMID- 15144568
TI  - Combination of Targeting Gene-ViroTherapy with 5-FU enhances antitumor efficacy
      in malignant colorectal carcinoma.
AB  - To improve the therapeutic effect of ONYX015, an E1B55kD-deleted replication
      competent adenovirus, ZD55 was constructed and armed with the therapeutic gene
      hTRAIL to form ZD55-hTRAIL, which was used for cancer therapy and which we call
      Targeting Gene-ViroTherapy. In vitro experiments with SW620, HCT116, and HT29
      colorectal carcinoma cell lines demonstrated that they were all sensitive to ZD55
      hTRAIL, and especially sensitive to ZD55-hTRAIL plus 5-fluorouracil (5-FU)
      treatment. In the SW620 xenograft tumor model, various treatment groups showed
      marked differences at week 11, with the tumor volume for the phosphate-buffered
      saline (PBS) treatment group >1700 mm3, for 5-FU > 1300 mm3, for ONYX015 1051.3
      mm3, for ZD55-hTRAIL 600.05 mm3, and for ZD55-hTRAIL plus 5-FU 230.2 mm3. At the
      end of week 14, tumor-bearing mice in the other groups almost all died, whereas
      all the mice in the combined treatment group were alive, with one mouse tumor
      free. By transmission electron microscopy (TEM) assay, most tumor cells treated
      with ONYX015 or with ZD55-hTRAIL singly or in combination with 5-FU were lysed
      due to viral propagation. RT-PCR analysis and immunohistochemistry examination
      revealed that hTRAIL was expressed in ZD55-hTRAIL-treated SW620 tumor tissue.
      Furthermore, no detectable hepatoxicity was found by serum enzyme level analysis.
      These results suggest that ZD55-hTRAIL alone or in combination with 5-FU may have
      potential clinical implications.

PMID- 15144570
TI  - IL-10 promoter nt -1082A/G polymorphism and human papillomavirus infection in
      cytologic abnormalities of the uterine cervix.
AB  - The role of A/G polymorphism at nucleotide -1082 in the interleukin-10 (IL-10)
      promoter was assessed by following the disease course of 253 patients who had had
      a routine diagnostic Hybrid Capture human papillomavirus (HPV) test because of
      cytologic or colposcopic abnormalities of the uterine cervix. At baseline, 97
      (78%) of the 125 high-risk HPV-positive and 83 (65%) of the 128 HPV-negative
      patients had equivocal cytologic atypia classified as P3 by the Papanicolaou
      classification, and the rest of the patients had mild colposcopic atypia with
      cytologic results of no oncogenic significance. In the high-risk HPV-infected
      patients, the frequency distribution of the nt -1082 genotypes (A/A: 28%; A/G:
      52%; G/G: 20%) did not differ significantly from that in the controls (A/A: 25%;
      A/G: 51%; G/G: 24%; p = 0.70). On the other hand, the nt -1082 G allele tended to
      decrease susceptibility to equivocal cytologic atypia unrelated to HPV infection
      (A/G: OR = 0.56 [95% CI: 0.31-1.02], G/G: OR = 0.27 [95% CI: 0.11-0.63], p for
      trend = 0.05). With respect to the development of high-grade cervical
      intraepithelial neoplasia (CIN), the established risk factors, such as high-risk
      HPV infection (RR = 104.6, 95% CI: 14.2-769.9) and cytologic atypia (RR = 9.6,
      95% CI: 2.34-39.7) but not the various nt -1082 genotypes (A/A: reference; A/G:
      RR = 1.11 [95% CI: 0.59-2.08]; G/G: RR = 0.62 [95% CI: 0.25-1.50]) were found to
      increase the risk for high-grade CIN. In conclusion, the nt -1082 polymorphism
      had no influence on the early phase of cervical carcinogenesis but may determine
      different susceptibilities to cervical abnormalities unrelated to HPV infection.

PMID- 15144571
TI  - Differential contribution of IL-1Ra isoforms to allele-specific IL-1Ra mRNA
      accumulation.
AB  - The interleukin-1 (IL-1) receptor antagonist (IL-1Ra) gene produces two isoforms
      of IL-1Ra, intracellular (icIL-1Ra) and secreted (sIL-1Ra). Distinct promoter
      regions control synthesis of each isoform. Five alleles of this gene, defined by
      sIL-1Ra intron 2 polymorphism, have been described. Although differences in IL
      1Ra protein production have been demonstrated in various tissues and cells
      obtained from individuals carrying allele 1 vs. allele 2, the underlying
      mechanisms of this discrepancy remain poorly understood. We hypothesize that one
      mechanism contributing to differences in protein levels may be allele-specific
      accumulation of icIL-1Ra or sIL-1Ra mRNA. Quantification of allele-specific
      differences in mRNA accumulation in colonic biopsies and peripheral blood
      mononuclear cells (PBMC) of heterozygous individuals shows that the amount of
      allele 1-specific icIL-1Ra mRNA averaged four times higher relative to allele 2.
      In transfection assays, gene expression directed by the allele 1-specific icIL
      1Ra promoter fragment was found to be greater than that directed by the allele 2
      promoter, suggesting that icIL-1Ra promoter activity contributes to the disparity
      in the allele-specific icIL-1Ra mRNA accumulation. Our data show that differences
      in the transcriptional regulation of icIL-1Ra alleles 1 and 2 may be involved in
      the production of icIL-1Ra protein. Disregulated icIL-1Ra production may play a
      role in chronic inflammatory diseases where the balance between IL-1 and IL-1Ra
      has been implicated as a key pathogenic mechanism.

PMID- 15144569
TI  - IFN-beta induces caspase-mediated apoptosis by disrupting mitochondria in human
      advanced stage colon cancer cell lines.
AB  - Various human colon cancer cell lines tested in vitro differed significantly in
      susceptibility to growth inhibition of recombinant human interferon-beta (rHuIFN
      beta). Two p53-mutant lines, COH and CC-M2, derived from high-grade colon
      adenocarcinoma, showed signs of apoptosis after treatment with 250 IU/ml of HuIFN
      beta in the culture medium. The similarly p53-mutated HT-29 line from a grade I
      adenocarcinoma showed no apoptosis, however, and only cell cycle G1/G0 or S phase
      retardation with 1000 IU/ml HuIFN-beta. After HuIFN-beta exposure, COH and CC-M2
      cells showed increased levels of Fas and FasL proteins, alteration of
      mitochondrial membrane potential, and activation of caspase-9, caspase-8, and
      caspase-3 in a time-dependent manner. Treatment of COH and CC-M2 cells with anti
      FasL antibodies or rFas/Fc fusion protein, however, could not prevent the
      apoptosis induced by HuIFN-beta. In contrast, cell-permeable specific inhibitors
      of the three caspases could inhibit the DNA fragmentation and cell death but not
      the mitochondrial membrane potential changes. Treatment with mitochondria
      stabilizing reagents could significantly abrogate the apoptosis and caspase
      activation induced by HuIFN-beta. These results suggest that in COH and CC-M2
      colon cancer cell lines, HuIFN-beta induces apoptosis mainly through
      mitochondrial membrane alteration and subsequent activation of the caspase
      cascade pathway, but not by the Fas/FasL interaction or the p53-dependent
      apoptotic mechanism.

PMID- 15144573
TI  - Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1,
      CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus.
AB  - Human papillomavirus (HPV) infection is associated with cervical cancer.
      Papillomaviruses can induce diseases ranging from warts and condylomata to
      lesions that can progress to malignant neoplasias. Cervical cancer is a serious
      problem in developing countries because it is usually not detected at an early
      stage. In Mexico, a woman dies every 2 hr from this malignancy. In a phase I/II
      clinical trial, we evaluated the potential use of the MVA E2 recombinant vaccinia
      virus to treat cervical intraepithelial neoplasia CIN 1, CIN 2, and CIN 3 lesions
      associated with human papillomavirus (HPV) infection. Seventy-eight women with
      CIN 1-, CIN 2-, and CIN 3-grade lesions were treated with either an MVA E2
      recombinant virus vaccine or with cryosurgery. Thirty-six women received the
      recombinant virus vaccine at a total of 10(7) MVA E2 virus particles injected
      directly into the uterus once every week over a 6-week period. Forty-two patients
      were treated with cryosurgery. Reduction of lesions was monitored weekly by
      colposcopy and cytologic analysis. The type of immune response after MVA E2
      injection was determined by measuring antibody titers against MVA E2 virus and
      the E2 protein, and by the presence of cytotoxic activity against cancer cells
      bearing papillomavirus DNA. The presence of papillomavirus was determined by with
      the hybrid capture method. Thirty-four of 36 patients showed complete elimination
      of precancerous lesions after treatment with the MVA E2 vaccine. In two patients,
      precancerous lesions were reduced from grade CIN 3 to CIN 1. Three other patients
      presented isolated koilocytes after treatment with MVA E2. Colposcopy revealed no
      lesions in 85% of patients, and only small aceto-white spots were detected in 15%
      of patients after treatment with MVA E2. All patients developed antibodies
      against the MVA E2 vaccine, and vaccination generated a specific cytotoxic
      response against HPV-transformed cells. Furthermore, 50% of patients showed no
      evidence of papillomavirus after treatment with MVA E2, while the remaining 50%
      showed persistence of HPV DNA, but at approximately only 10% of the original
      viral load. The presence of cells cytotoxic to HPV-transformed cells, and the
      generation of antibodies against MVA E2, correlated with the elimination of
      lesions and with a remarkable reduction of HPV viral load in all patients treated
      with MVA E2. Additionally, the MVA E2 vaccine did not produce any apparent side
      effects in any of the patients treated. Cryosurgery eliminated the lesions of CIN
      1 in all patients, but patients so treated did not develop cytotoxic activity
      against cancer cells. These results show that therapeutic vaccination with MVA E2
      vaccine is an excellent prospective means for stimulating the immune system and
      causing the regression of precancerous CIN 1, CIN 2, and CIN 3 lesions when the
      vaccine is given locally.

PMID- 15144574
TI  - A novel strategy to modify adenovirus tropism and enhance transgene delivery to
      activated vascular endothelial cells in vitro and in vivo.
AB  - To assess the possibilities of retargeting adenovirus to activated endothelial
      cells, we conjugated bifunctional polyethylene glycol (PEG) onto the adenoviral
      capsid to inhibit the interaction between viral knob and coxsackie-adenovirus
      receptor (CAR). Subsequently, we introduced an alphav integrin-specific RGD
      peptide or E-selectin-specific antibody to the other functional group of the PEG
      molecule for the retargeting of the adenovirus to activated endothelial cells. In
      vitro studies showed that this approach resulted in the elimination of transgene
      transfer into CAR-positive cells, while at the same time specific transgene
      transfer to activated endothelial cells was achieved. PEGylated, retargeted
      adenovirus showed longer persistence in the blood circulation with area under
      plasma concentration-time curve (AUC) values increasing 12-fold compared to
      unmodified virus. Anti-E-selectin antibody-PEG-adenovirus selectively homed to
      inflamed skin in mice with a delayed-type hypersensitivity (DTH) inflammation,
      resulting in local expression of the reporter transgene luciferase. This is the
      first study showing the benefits of PEGylation on adenovirus behavior upon
      systemic administration. The approach described here can form the basis for
      further development of adenoviral gene therapy vectors with improved
      pharmacokinetics and increased efficiency and specificity of therapeutic gene
      transfer into endothelial cells in disease.

PMID- 15144575
TI  - Stable transgene expression in tumors and metastases after transduction with
      lentiviral vectors based on human immunodeficiency virus type 1.
AB  - The relatively low efficiency of target cell transduction and variations in the
      stability of transgene expression by retroviral vectors based on the Moloney
      murine leukemia virus (MoMLV) are major impediments to the use of such vectors in
      cancer gene therapy approaches. The present study was designed to investigate the
      stability and efficiency of transgene expression in human lung and breast cancer
      cell lines transduced with vectors based on human immunodeficiency virus type 1
      (HIV-1) in vitro and in vivo in nude mouse models of metastasis. H460 lung
      carcinoma cells and MDA-MB-231 breast carcinoma cells were transduced with
      lentiviral vectors encoding enhanced green fluorescent protein (EGFP) and beta
      galactosidase (beta-Gal), respectively. Transduced H460 cells were administered
      to nude mice by either intravenous or subcutaneous injection and MDA-MB-231 cells
      were implanted orthotopically into the mammary fat pad of such mice to induce
      primary tumor and metastatic lung tumor formation. High-level EGFP expression was
      maintained in transduced H460 cells in metastatic lung nodules for up to 6 weeks
      and transgene expression in vitro persisted for at least 23 days after retrieval
      of EGFP-positive H460 cells from the lungs of tumor-bearing mice and subsequent
      cultivation in vitro. Likewise, beta-Gal expression levels in metastatic MDA-MB
      231 cells in lungs remained high for up to 11 weeks. Southern blot analyses
      carried out with DNA from lung nodules showed that proviral DNAs in H460 cells
      were maintained stably over many cell generations and during subsequent
      reimplantation in vivo. However, molecular analyses revealed variations in
      transgene copy numbers and expression levels among individual lung clones. These
      results demonstrate the usefulness of HIV-1-based lentiviral vectors for
      sustained and stable transgene expression in human lung and breast cancer cell
      lines in vitro and in vivo.

PMID- 15144577
TI  - Basic fibroblast growth factor enhances transduction, distribution, and axonal
      transport of adeno-associated virus type 2 vector in rat brain.
AB  - The ubiquitous expression of cell surface heparan sulfate proteoglycan, a binding
      receptor for adeno-associated virus type 2 (AAV-2), may account for the broad
      host range of this vector. Because the fibroblast growth factor receptor type 1
      has been postulated to be a coreceptor for successful AAV-2 entry into host
      cells, we designed a strategy to investigate whether coadministration of this
      virus with basic fibroblast growth factor (bFGF) can enhance AAV-2-mediated gene
      delivery. We injected AAV-2-thymidine kinase (AAV-2-TK) vector into rat striata
      and checked whether coinjection with bFGF enhanced transduction and/or enlarged
      the area of transgene expression. Immunostaining confirmed the tropism of AAV-2
      TK for neurons. The previous injection (7 days before vector delivery) of bFGF
      had no major impact on vector distribution area. However, when the vector was
      coinjected with bFGF, the right striatum showed an average viral transduction
      volume of 5 mm(3), which was more than 4-fold larger when compared with the left
      side (AAV-2-TK plus phosphate-buffered saline). This result clearly indicates
      that simultaneous injection of bFGF with AAV-2-TK can greatly enhance the volume
      of transduced tissue, probably by way of a competitive block of AAV-2-binding
      sites within the striatum. Robust TK immunoreactivity was also observed in the
      globus pallidus, which receives anterograde projections from the striatum. We
      propose that postsynaptic transport of recombinant particles was likely
      responsible for the distribution of TK in the globus pallidus on both bFGF
      treated and untreated sides. In summary, we found that bFGF acts as an adjuvant
      for distribution of AAV-2 in rat brain.

PMID- 15144576
TI  - Subunit-specific coordinate upregulation of sodium pump activity in alveolar
      epithelial cells by lentivirus-mediated gene transfer.
AB  - Resolution of alveolar edema depends on active ion transport by sodium pumps
      located on the basolateral surface of alveolar epithelial cells (AECs),
      suggesting that upregulation of sodium pump activity may facilitate clearance of
      edema fluid. We have investigated the use of lentiviral vectors to augment sodium
      pump activity via gene transfer of sodium pump subunits to AECs. Full-length cDNA
      for the alpha(1) or beta(1) subunit of rat Na(+),K(+)-ATPase was cloned into the
      lentiviral vector pRRLsin.hCMV.IRES.EGFP. Rat AECs in primary culture were
      transduced on day 4 with lentiviral vectors pseudotyped with vesicular stomatitis
      virus glycoprotein G. Transduction with lentiviral vectors encoding either
      alpha(1) subunit (Lenti-alpha(1)-EGFP) or beta(1) subunit (Lenti-beta(1)-EGFP)
      led to dose-dependent increases in mRNA and protein for the corresponding
      subunit. Transduction with Lenti-beta(1)-EGFP was accompanied by coordinate
      upregulation of endogenous alpha(1) expression, whereas endogenous beta(1)
      expression was unchanged after transduction with Lenti-alpha(1)-EGFP. Consistent
      with these findings, transduction with Lenti-beta(1)-EGFP, but not Lenti-alpha(1)
      EGFP, led to augmentation of sodium pump activity as a result of increases in
      Na(+),K(+)-ATPase holoenzyme. Sodium pump alpha(2) subunit and sodium channel
      protein did not change after Lenti-beta(1)-EGFP transduction. These results
      demonstrate that overall sodium pump activity can be efficiently upregulated in
      AECs specifically via gene transfer of the sodium pump beta(1) subunit and
      support the feasibility of lentivirus-mediated gene transfer to augment alveolar
      fluid clearance.

PMID- 15144578
TI  - Nonionic polymeric micelles for oral gene delivery in vivo.
AB  - The main aim of this study was to investigate the feasibility of using nonionic
      polymeric micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene
      oxide) (PEO-PPO-PEO) as a carrier for oral DNA delivery in vivo. The size and
      appearance of DNA/PEO-PPO-PEO polymeric micelles were examined, respectively, by
      dynamic light scattering and atomic force microscopy, and their zeta potential
      was measured. Expression of the delivered lacZ gene in various tissues of nude
      mice was assessed qualitatively by 5-bromo-4-chloro-3-indolyl-beta-D
      galactopyranoside staining of sections and quantitatively by measuring enzyme
      activity in tissue extracts, using the substrate of beta-galactosidase,
      chlorophenol red-beta-D-galactopyranoside. In addition, the types of cells
      expressing the lacZ gene in the duodenum were identified by histological
      analysis. DNA/PEO-PPO-PEO polymeric micelles are a single population of rounded
      micelles with a mean diameter of 170 nm and a zeta potential of -4.3 mV. Duodenal
      penetration of DNA/PEO-PPO-PEO polymeric micelles was evaluated in vitro by
      calculating the apparent permeability coefficient. The results showed a dose
      independent penetration rate of (5.75 +/- 0.37) x 10(-5) cm/sec at low DNA
      concentrations (0.026-0.26 microg/microl), but a decrease to (2.89 +/- 0.37) x
      10(-5) cm/sec at a concentration of 1.3 microg/microl. Furthermore, when 10 mM
      RGD peptide or 10 mM EDTA was administered before and concurrent with the
      administration of DNA/PEO-PPO-PEO polymeric micelles, transport was inhibited
      ([0.95 +/- 0.57] x 10(-5) cm/sec) by blocking endocytosis or enhanced ([29.8 +/-
      5.7] x 10(-5) cm/sec) by opening tight junctions, respectively. After oral
      administration of six doses at 8-hr intervals, the highest expression of
      transferred gene lacZ was seen 48 hr after administration of the first dose, with
      gene expression detected in the villi, crypts, and goblet cells of the duodenum
      and in the crypt cells of the stomach. Reporter gene activity was seen in the
      duodenum, stomach, and liver. Activity was also seen in the brain and testis when
      mice were administered 10 mM EDTA before and concurrent with DNA/PEO-PPO-PEO
      polymeric micelle administration. lacZ mRNA was detected in these five organs and
      in the blood by reverse transcription-polymerase chain reaction. Taken together,
      these results show efficient, stable gene transfer can be achieved in mice by
      oral delivery of PEO-PPO-PEO polymeric micelles.

PMID- 15144579
TI  - Glioma-specific and cell cycle-regulated herpes simplex virus type 1 amplicon
      viral vector.
AB  - We have engineered a novel herpes simplex virus type 1 (HSV-1)-based amplicon
      viral vector, whereby gene expression is controlled by cell cycle events. In
      nondividing cells, trans-activation of the cyclin A promoter via interaction of
      the Gal4/NF-YA fusion protein with the Gal4-binding sites is prevented by the
      presence of a repressor protein, cell cycle-dependent factor 1 (CDF-1). CDF-1 is
      specifically expressed during the G(0)/G(1) phase of the cell cycle and its
      binding site is located within the cyclin A promoter. In actively proliferating
      cells, trans-activation could take place because of the absence of CDF-1. Our
      results showed that when all these cell cycle-specific regulatory elements are
      incorporated in cis into a single HSV-1 amplicon plasmid vector backbone (pC8
      36), reporter luciferase activity is greatly enhanced. Transgene expression
      mediated by this series of HSV-1 amplicon plasmid vectors and amplicon viral
      vectors could be regulated in a cell cycle-dependent manner in a variety of cell
      lines. In a further attempt to target transgene expression to a selected group of
      actively proliferating cells such as glial cells, we have replaced the
      cytomegalovirus promoter of the pC8-36 amplicon plasmid with the glial cell
      specific GFAP enhancer element. With this latter viral construct, cell type
      specific and cell cycle-dependent transgene expression could subsequently be
      demonstrated specifically in glioma-bearing animals. Taken together, our results
      suggest that this series of cell cycle-regulatable HSV-1 amplicon viral vectors
      could potentially be adapted as useful tools for the treatment of human cancers.

PMID- 15144580
TI  - Genetic replacement of the adenovirus shaft fiber reduces liver tropism in
      ovarian cancer gene therapy.
AB  - Approaches to alter the native tropism of adenoviruses (Ads) are beneficial to
      increase their efficacy and safety profile. Liver tropism is important with
      regard to potential clinical toxicity in humans. Ad5/3 chimeras in which the Ad5
      knob is substituted by the Ad3 knob, such as Ad5/3luc1, have been recently shown
      to increase infectivity of ovarian cancer cell lines and primary tumor cells,
      which express low levels of the coxsackie-adenovirus receptor (CAR), without
      increasing infectivity of liver cells. A novel strategy to address the problem of
      liver uptake and improve the tumor/liver ratio is genetic replacement of the Ad
      fiber shaft. Ad5.Ad3.SH.luc1 is an Ad5-based vector that contains the fiber shaft
      from Ad serotype 3 but the fiber knob from Ad serotype 5. To compare tumor/liver
      of Ad5.Ad3.SH.luc1 and Ad5/3luc1 in vivo, we created three different tumor and
      treatment models of ovarian cancer in mice, simulating intraperitoneal and
      intravenous administration of tumors. Ad5.Ad3.SH.luc1 displayed the lowest liver
      tropism of all viruses in all models tested. Intravenous administration of all
      viruses resulted in higher tumor transduction rates compared to intraperitoneal
      administration. Genetic shortening of the Ad5 fiber shaft significantly increases
      relative tumor/liver gene transfer. This could improve the effective tumor dose
      and reduce side effects, thereby increasing the bioavailability of therapeutic
      agents.

PMID- 15144582
TI  - [Metabolic syndrome is threatening the health of mankind].

PMID- 15144583
TI  - [The development of minimally invasive cardiac surgery in China].

PMID- 15144581
TI  - Characterization of a family of chimpanzee adenoviruses and development of
      molecular clones for gene transfer vectors.
AB  - The high prevalence of preexisting immunity to the commonly used adenoviral
      vectors, as well as the requirement for readministration of vector for multiple
      therapeutic applications, necessitates the development of a panel of
      immunologically distinct adenoviral vectors against which neutralizing antibodies
      are rare in human populations. We have completely sequenced three chimpanzee
      derived adenoviruses, Pan 5, Pan 6, and Pan 7, and have molecularly cloned E1
      deleted vector genomes from each as bacterial plasmids. All the E1-deleted
      vectors were grown to high titer in HEK 293 cells. Neutralizing antibodies to the
      chimpanzee adenoviral vectors were not detected in serum samples from human
      subjects. In vitro cross-neutralization using rabbit antisera and in vivo
      readministration experiments in mice demonstrated that antibodies against Pan 5,
      Pan 7, or Pan 9 cross-neutralize one another but do not neutralize Pan 6. These
      results indicate that chimpanzee adenoviral vectors may be useful as vaccines or
      gene therapy vectors in human populations and should allow applications that
      require multiple vector administrations.

PMID- 15144584
TI  - [A comparison of the application of two working definitions of metabolic syndrome
      in Chinese population].
AB  - OBJECTIVE: To compare the significance of the application of the working
      definition for metabolic syndrome (MS) proposed by the World Health Organization
      (WHO) in 1999 and the one proposed by the Third Report of the National
      Cholesterol Education Program Expert Panel on Detection, Evaluation, and
      Treatment of High Blood Cholesterol in Adults (ATP III) in 2001. METHODS: Data of
      2048 subjects, aged 20-74, 896 males and 1152 females, with complete laboratory
      data, including plasma glucose, lipid profile, blood pressure, serum insulin,
      urine albumin and creatinine, were gathered from the data of baseline survey on
      obesity and its co-morbidities conducted in Huayang and Caoyang communities,
      Shanghai, from 1999 to 2001. MS was diagnosed according to these two definitions
      respectively. RESULTS: (1) The age-adjusted MS prevalence rates were 17.14% and
      10.95% according to the WHO (1999) and ATP III (2001) respectively, the former
      being significantly higher than the latter. (2) A total of 445 subjects were
      diagnosed as having MS. The agreement in the diagnosis of MS using two
      definitions was about 45.17%. 42.02% of the subjects had MS only under the WHO
      (1999) definition, while 12.81% of the subjects had MS under the ATP III (2001)
      definition. (3) The prevalence rate of hyperglycemia and central obesity as
      defined by WHO (1999) definition were 1.74 and 4.38 times higher than those
      defined by ATP III (2001) definition (16.74% vs 9.57%, 33.04% vs 7.54%
      respectively). (4) In comparison with non-MS subjects, the body mass index, waist
      to-hip ratio, blood pressure, blood glucose, insulin resistant index (HOMA-IR),
      and albumin-to-creatinine ratio were all significantly increased in MS subjects.
      CONCLUSION: Both definitions for MS can reflect the clustering degree of risk
      factors of cerebrovascular and cardiovascular diseases. The WHO definition of MS
      can better reflect the characteristics of MS in Chinese than the definition
      proposed by ATP III, however it needs more measurements and costs more. A simple
      method with high detection ability remains to be worked out.

PMID- 15144585
TI  - [Metabolic syndrome strongly linked to stroke in Chinese].
AB  - OBJECTIVE: To assess the association of the metabolic syndrome with stroke in
      Chinese using the definition of ATP III, and revised definition according to
      Chinese criteria for abdominal obesity. METHODS: Multi-center case control study,
      1934 first-ever-stroke patients (Atherothrombosis, lacunar infarction, and
      intracerebral hemorrhage) aged 30 to 74 years were sequentially recruited. And
      1839 age, gender and geographically matched subjects were included as controls.
      RESULTS: The prevalence of metabolic syndrome defined by either ATP III or
      Chinese criteria was significantly increasing in patients with lacunar
      infarction, cerebral atherosclerosis, or intracerebral hemorrhage than control
      subjects. After age- and sex-adjusted and further adjusted age, sex, total
      cholesterol, smoking, drinking, and education levels, the metabolic syndrome
      defined by ATP III criteria was associated with a 2.7 to 4.3 fold and 2.5 to 4.0
      fold higher risk of the three stroke subtypes, respectively. CONCLUSION: the
      metabolic syndrome defined by ATP III and revised according to Chinese criteria
      of abdominal obesity was positively associated with the risk of stroke in our
      case control study. This study underscores the need for well-designed prospective
      study in Chinese to give further evidence to the link between metabolic syndrome
      and stroke.

PMID- 15144586
TI  - [Peroxisome proliferator-activated receptor gamma C-161T polymorphism and carotid
      artery atherosclerosis in metabolic syndrome].
AB  - OBJECTIVE: To assess the relationship between PPAR gamma C161-T polymorphism and
      Carotid Atherosclerosis in metabolic Syndrome (MS). METHODS: Polymerase chain
      reaction-restricted fragments length polymorphism was used to study the
      distribution of the PPAR gamma C161-T polymorphism in 248 metabolism syndrome,
      163 essential hypertension (EH) and 115 type 2 diabetes mellitus (DM) patients
      and 121 normal controls. Fasting insulin (FINS), fasting blood glucose (FBG),
      uric Acid (UA), plasma lipids and ultrasonography for carotid artery were
      examined. RESULTS: Waistline and BMI were significantly higher in MS compared
      with those in control, EH and DM (P < 0.01). systolic blood pressure (SBP),
      diastolic blood pressure (DBP) and pulse pressure (PP) were markedly higher in MS
      and EH compared with those in DM and control (P < 0.01). The frequencies of the
      CC, CT and TT were 74.6%, 21.8% and 3.6% in MS respectively, The frequencies of
      the CC was significantly higher in MS compared with that in control, but T allele
      carrier (CT + TT) was significantly lower compared with control, DM and EH (P <
      0.05 or P < 0.01). In MS, CC genotype had significantly increased the intima
      media thickness (IMT) of common carotid artery and plaque index compared with CT
      + TT (IMT: 0.84 mm +/- 0.3 mm vs 0.66 mm +/- 0.19 mm; plaque index: 2.19 +/- 1.21
      vs 1.66 +/- 1.36, P < 0.05), CC genotype had significantly increased plaque index
      compared with CT + TT in EH and DM (plaque index: EH: 1.55 +/- 1.23 vs 1.29 +/-
      0.92; DM: 1.57 +/- 1.2 vs 1.18 +/- 0.85, P < 0.05); CC genotype had significantly
      higher SBP compared with CT + TT in EH (P < 0.05), CC genotype had significantly
      increased plaque index in MS than that in DM and EH (P < 0.01), CC genotype had
      significantly increased IMT in MS compared with DM. CC genotype had significantly
      higher SBP and PP compared with CT + TT in MS (SBP: 155 mm Hg +/- 23 mm Hg vs 145
      mm Hg +/- 21 mm Hg; PP: 69 mm Hg +/- 8 mm Hg vs 58 mm Hg +/- 8 mm Hg, 1 mm Hg =
      0.133 kPa, P < 0.05). CONCLUSION: In MS, CC genotype was prone to lesion of
      carotid artery, but CT + TT may reduce lesion of carotid artery, which implicates
      that PPAR gamma C161-T may play a important role in carotid artery
      arteriosclerosis.

PMID- 15144588
TI  - [Interaction of ApoE and LDL-R gene polymorphisms and alcohol drinking and
      smoking on coronary heart disease].
AB  - OBJECTIVE: To investigate the association between the ApoE and LDLR-R gene loci
      on coronary heart disease (CHD) and their interaction with alcohol drinking and
      smoking in Hans of Chinese. METHODS: A questionnaire survey of the behaviors of
      smoking and drinking, dietary custom, and anamnesis, was conducted among 146
      cases of CHD, aged 64 +/- 11, and 340 controls, aged 63 +/- 12. Peripheral blood
      samples were collected and the total DNAs were extracted. The levels of
      triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were examined. The ApoE
      genotype was identified by the method of multiplex amplification refractory
      mutation system and AvaII polymorphisms of the LDL-R gene were detected by using
      the method of polymerase chain reaction-restriction fragment length polymorphism.
      The interaction between the genes and alcohol drinking and smoking was analyzed
      by using multivariate logistic regression models. RESULTS: (1) Both the systolic
      blood pressure and diastolic blood pressure of the CHD patients (132 mm Hg +/- 21
      mm Hg, and 81 mm Hg +/- 13 mm Hg, 1 mm Hg = 0.133 kPa) were significantly higher
      than those of the controls (123 mm Hg +/- 17 mm Hg and 77 mm Hg +/- 11 mm Hg,
      both P < 0.05). The level of TG was 1.6 +/- 0.9 mmol/L in the CHD group,
      significantly higher than that in the control group (1.4 +/- 0.8 mmol/L, P <
      0.05). However, there was no difference in the levels of TC, LDL-C, and HDL-C
      between the 2 groups (all P > 0.05). (2) For the ApoE gene, the frequencies of
      E4/3 genotype and epsilon 4 allele were 24.0% and 13.4% respectively in the CHD
      group, both significantly higher than those in the control group (12.9% and 7.2%
      respectively, both P < 0.05). For the LDLR-AvaII locus, no difference was found
      in different genotypes between the CHD and control groups. However, the
      proportion of those with epsilon 4 locus and AvaII(+) locus simultaneously was
      60% in the CHD group, significantly higher than in the control group (31.8%, P <
      0.05). (3) After adjustment of confounding variables, such as age, sex, blood
      pressure, and body mass index, the binary logistic analysis showed a significant
      gene-environment interaction (P < 0.05). The OR value were: for epsilon 4
      AvaII(+): 2.99 (95% CI: 1.36 approximately 6.66, P < 0.01), for epsilon 3-often
      drinking: 2.60 (95% CI: 1.35 approximately 5.02, P < 0.01), for epsilon 3-smoking
      2.58 (95% CI: 1.16 approximately 5.71, P < 0.05), for epsilon 4-stopped smoking
      3.12 (95% CI: 1.23 approximately 8.09, P < 0.05), for epsilon 4-smoking: 5.30
      (95% CI: 1.21 approximately 23.22, P < 0.05), and for AvaII(+)-often drinking:
      2.49 (95% CI: 1.12 approximately 5.52, P < 0.05) respectively. CONCLUSION: The
      carriers of epsilon 3, epsilon 4 or AvaII(+) alleles would have higher risk of
      suffering from CHD if they are drink alcohol or smoke heavily.

PMID- 15144587
TI  - [The protective effect of interleukin-1 receptor antagonist on postischemic
      reperfused myocardium and its possible mechanism].
AB  - OBJECTIVE: To observe the dynamic changes of plasma inflammatory cytokine
      interleukin-1 beta (IL-1 beta) in patients with acute myocardiac infarction (AMI)
      before and after recanalization of the infarct related artery (IRA) and to
      observe the effect of recombinant human IL-1 receptor antagonist (rhIL-1ra) on
      the postischemic reperfused myocardium in experimental rabbits. METHODS: (1)
      ELISA was used to measure the plasma IL-1 beta of 22 AMI patients, 20 males and 2
      females, aged 64 +/- 12, before emergency percutaneous coronary intervention
      (PCI), and 12 hours and 24 hours after-intervention, and measure the plasma IL-1
      beta of 8 healthy controls, 6 males and 2 females, aged 56 +/- 9. (2) Forty
      rabbits underwent ligation of the left circumflex branch of coronary artery (LCX)
      for 50 minutes and reperfusion for 4 hours after the ligatures were untied. The
      rabbits were randomly divided into 4 groups of 10 rabbits to be injected into the
      left ventricle immediately before the reperfusion with rhIL-1ra 10 mg/kg (group
      A), 20 mg/kg (group B), or 40 mg/kg (group C), and normal saline (control group)
      respectively. After reperfusion of 4 hours, the LCX was re-ligated. Evans blue
      was injected into the left ventricle. 15% KCl was injected intravenously to kill
      the rabbits. Their hearts were taken out to weigh the non-ischemic, ischemic, and
      necrotic cardiac muscles so as to calculate the infarct size. The myoperoxidase
      (MPO) activity was measured by colorimetry. Sections of myocardium were made. The
      number of apoptotic cardiomyocytes was evaluated by TUNEL method. The apoptotic
      rate of cardiomyocyte was measured by annexin V method. The DNA expression of
      myocardium was detected by DNA laddering method. The expressions of Bcl-2 and Bax
      apoptosis genes were assessed. RESULTS: (1) The average plasma IL-1 beta level of
      the 22 AMI patients before emergency PCI was significantly higher than that of
      the controls (28 pg/ml +/- 9 pg/ml vs. 20 pg/ml +/- 11 pg/ml, P < 0.05), and
      became the highest 12 hours after the intervention (86 pg/ml +/- 14 pg/ml), and
      the high level lasted to 24 hours after emergency PCI. (2) In the ischemia
      reperfusion rabbit model, the infarct size was 47% +/- 7% in the group A, 34% +/-
      8% in the group B, 31% +/- 6% in the group C, and 61% +/- 11% in the control
      group (P < 0.05, 0.01, and 0.01 respectively). The activity of myocardial MPO was
      16.6 +/- 3.6 min(-1).g.w.w(-1) in the group A, 10.9 min(-1).g.w.w(-1) +/- 1.9
      min(-1).g.w.w(-1) in the group B, 7.8 min(-1).g.w.w(-1) +/- 2.2 min(-1).g.w.w(-1)
      in the group C, and 20.5 min(-1).g.w.w(-1) +/- 4.5 min(-1).g.w.w(-1) in the
      control group (P < 0.05, 0.01, and 0.01 respectively). The cardiomyocyte
      apoptosis evaluated by TUNEL was 38.3 n/HP +/- 7.4 n/HP in the group A, 25.6 n/HP
      +/- 6.8 n/HP in the group B, 12.2 n/HP +/- 3.3 n/HP in the group C, and 44.4 n/HP
      +/- 9.5 n/HP in the control group (P < 0.05, and P < 0.01 respectively in
      comparison between the group B and the control group and between the group C and
      the control group). The apoptotic rate by annexin V method was 11.6% +/- 2.7% in
      the group A; 7.7% +/- 2.4% in the group B, 4.7% +/- 1.4% in the group C, and
      15.6% +/- 3.5% in the control group (P < 0.05, 0.01, and 0.01 respectively). DNA
      electrophoresis showed scaling ladder pattern only in the control group. The
      fluorescent density of the apoptosis gene Bax in myocardium was 24.9 +/- 8.2 in
      the group A; 15.5 +/- 3.4 in the group B, 10.6 +/- 2.5 in the group C, and 33.3
      +/- 9.4 in the control group (P = 0.0298, 0091, and 0052 respectively) and no
      significant difference in the expression of Bcl-2 was shown among the 4 groups.
      Myocardial MPO was correlated with cardiomyocyte apoptosis (r = 0.86 by TUNEL, P
      < 0.01; r = 0.75 by Annexin V method, P < 0.05). CONCLUSION: Inflammatory
      cytokine IL-1 beta is involved in myocardial ischemia-reperfusion injury. With
      potential therapeutic value in prevention and treatment of ischemia-reperfusion
      injury to myocardium, rhIL-1ra may reduce myocardial ischemia-reperfusion injury
      by suppression of cardiomyocytes apoptosis mediated by IL-als; 0.86 by TUNEL, P <
      0.01; r = 0.75 by Annexin V method, P < 0.05). CONCLUSION: Inflammatory cytokine
      IL-1 beta is involved in myocardial ischemia-reperfusion injury. With potential
      therapeutic value in prevention and treatment of ischemia-reperfusion injury to
      myocardium, rhIL-1ra may reduce myocardial ischemia-reperfusion injury by
      suppression of cardiomyocytes apoptosis mediated by IL-1.

PMID- 15144589
TI  - [High efficient generation of recombinant adenovirus containing human Fas gene
      using a method of homologous recombination in bacteria].
AB  - OBJECTIVE: To generate recombinant adenovirus with human Fas gene and transfect
      the Fas gene into keloid-derived fibroblasts to take place of the dysfunctional
      Fas gene, reconstruct the blocked Fas signal. METHODS: We used a new bacterial
      homologous recombination system (Ad-Easy system) to construct recombinant
      adenovirus vector. Fas gene was cut down from the PMD-T-Fas plasmid and then
      transferred to track plasmid. Recombination was successfully completed in
      bacteria BJ5183 and recombinant adenovirus was produced in 293 cells. Then we
      infected keloid derived fibroblasts and compared the expression of Fas protein.
      Finally, we detected the function of newly produced Fas protein. RESULTS: We
      successfully constructed the recombinant adenovirus with Fas gene and detected
      its highly expressed Fas protein in infected keloid derived fibroblasts. Obvious
      apoptosis was also detected in infected keloid derived fibroblasts exposed to
      FasMcab. CONCLUSION: (1) The recombinant adenovirus with Fas gene can transfect
      the Fas gene into keloid-derived fibroblasts and highly improved the expression
      of Fas protein. The newly expressed Fas gene can reconstruct the blocked Fas
      signal. (2) The correlation between keloid and Fas gene was further proved and it
      may paves a sound foundation for further gene therapy in keloid.

PMID- 15144592
TI  - [Connective tissue growth factor synergistically with transforming growth factor
      beta 1 to promote renal fibrosis].
AB  - OBJECTIVE: To investigate the influence of CTGF and TGF-beta(1) on the synthesis
      and secretion of matrix metalloproteinase-2 (MMP-2) and myofibrotic activation in
      renal fibroblasts. METHODS: Equal numbers of renal fibroblasts (NRK-49F) were
      planted and divided into vechile, CTGF treated alone, TGF-beta(1) treated alone,
      and CTGF plus TGF-beta(1) treated groups. Gelatin zymography and Western-blot
      analysis were used for assay of the MMP-2 activity and protein level in the
      supernatant cultured medium, respectively. The levels of MMP-2 mRNA were assessed
      by real time-PCR. Western-blot analysis was carried out to measure the expression
      of alpha-smooth muscle actin (alpha-SMA), a maker protein of myofibroblast in
      cells, and the levels of extracellular matrix (ECM) component Fibronectin in
      supernantant medium. RESULTS: The activity and protein level of MMP-2 were no
      significant difference between the groups when cells were stimulated for 24
      hours. While cells were stimulated for 48 hours, 100 ng/ml CTGF and 5 ng/ml TGF-
      beta(1) induce a increase in MMP-2 activity and protein levels compared with
      vechile, respectively (P < 0.05); different dose of CTGF plus TGF-beta(1) had the
      tendency to suppress MMP-2 activity and protein level, and a significant decrease
      was seen in 50 ng/ml CTGF plus 5 ng/ml TGF-beta(1) group, 100 ng/ml CTGF plus 5
      ng/ml TGF-beta(1) group compared with CTGF group and TGF-beta(1) group,
      respectively (P < 0.05). When cells were stimulated for 12 hours, the levels of
      MMP-2 mRNA were increased significantly in 100 ng/ml CTGF group and 5 ng/ml TGF
      beta(1) group compared with vechile respectively beta(1.72), 1.68 vs 1.29, (P <
      0.01), decreased significantly in CTGF plus TGF-beta(1) group compared with CTGF
      group and TGF-beta(1) group, respectively (0.67 vs 1.72, 1.68, P < 0.01). 100
      ng/ml CTGF had no prominent effect on the expression of alpha-SMA in cells and FN
      in supernatant medium (P > 0.05), whereas 5 ng/ml TGF-beta(1) significantly
      stimulated both the expression of alpha-SMA and FN (P < 0.05), and CTGF plus TGF
      beta(1) induced more alpha-SMA and FN compared with TGF-beta(1) (P < 0.05).
      CONCLUSION: CTGF synergistically with TGF-beta(1) to induce the formation of
      myofibroblasts and down-regulate the production of MMP-2 in renal fibroblast.

PMID- 15144593
TI  - [Transforming growth factor beta 1 modulates connective tissue growth factor
      expression via Smad2 signaling pathway in podocyte in vitro].
AB  - OBJECTIVE: To assess the expression of connective tissue growth factor (CTGF),
      and the signaling pathway for the regulation of CTGF by transforming growth
      factor beta1 (TGF beta(1)) in podocytes. METHODS: In this study, we observed the
      effects of three potent profibrotic growth factors-TGF beta(1), Platelet-derived
      growth factor (PDGF), and Angiotensin II (AngII) on the expression of CTGF
      protein by Western blot analysis in cultured mouse podocytes, which is one of the
      most important cell construction of glomerular filter barrier, and we also
      investigated the underlying ERK and Smads signaling pathway through which TGF
      beta(1) regulates CTGF expression. The levels of CTGF mRNA were assayed by RT
      PCR. RESULTS: Basal levels of CTGF protein were observed in cultured podocytes,
      treatment with 20 ng/ml PDGF and 10(-6) mol/L Ang. II for 24 h did not stimulate
      the expression of CTGF protein compared with control (P > 0.05), but
      significantly increase in levels of CTGF protein were seen in 1 ng/ml TGF beta(1)
      treated cells compared with with control (P < 0.05), and the levels of CTGF were
      up-regulated in a TGF beta(1) dose-dependent manner; The level of CTGF mRNA was
      also stimulated by 1 ng/ml TGF beta(1) at 12 h. 1 ng/ml TGF beta(1) induced
      phosphorylation of Smad(2) and ERK(1/2), and both reached the peak at 30 min;
      suppression of phosphorylation of Smad(2) with Staurosporine, a Serine/Threonine
      kinase inhibitor, diminished TGF beta(1)-triggered expression of CTGF protein,
      while blockade of phosphorylation of ERK(1/2) with PD98059, a specific ERK(1/2)
      activation inhibitor, did not decrease the TGF beta(1)-triggered expression of
      CTGF protein. CONCLUSION: TGF beta(1) stimulated the expression of CTGF protein
      via Smad(2)-dependent and ERK(1/2)-independent signaling pathway in podocyte in
      vitro.

PMID- 15144594
TI  - [Coronary resistance system in evaluation of microvascular dysfunction after
      intracoronary microembolization: an experimental study].
AB  - OBJECTIVE: To assess the microvascular function of coronary artery after
      intracoronary microembolization using coronary resistance system. METHODS: The
      left anterior descending coronary artery (LAD) of 10 pigs weighing 21 kg-25 kg
      were embolized by repetitive injection of microspheres 45 micro m in diameter
      through a 2.8F Tracker catheter. Intra-vascular ultrasound (IVUS) images,
      intracoronary Doppler and pressure signals in the middle segment of LAD were
      acquired by use of intracoronary ultrasound imaging catheter, Doppler flow wire
      and pressure wire separately. Intracoronary bolus injection of 18 micro g
      adenosine was administered to maximally vasodilate the coronary arterial bed
      through the 2.8F Tracker catheter. The resting and hyperemic signals were
      acquired respectively before microembolization and in different levels of
      microembolization. Coronary resistance system reflecting the resistance to
      pulsatile coronary flow was established by a self-made software of PC system. The
      resting and hyperemic CR parameters included average resting coronary resistance
      (rCR) and average minimal coronary resistance (min-CR), the first-harmonic rCR
      and min-CR, the first-harmonic rCR orientation and min-CR orientation, and so on.
      Factor analysis was performed to extract the best coronary parameter from the
      coronary resistance parameters. RESULTS: Factor analysis showed that the first
      harmonic rCR and first-harmonic min-CR were correlated better with the first
      component extracted from the resting and hyperemic CR parameters than rCR and min
      CR, with the correlation coefficient being 0.913 and 0.950 in the first-harmonic
      CR and first-harmonic min-CR respectively. No significant difference in min-CR
      was found between the value at the dosage of 5 x 10(4) microspheres and that
      before microembolization. The min-CR value increased markedly from 271 mm Hg.ml(
      1).s(-1) +/- 99 mm Hg.ml(-1).s(-1) at the dosage of injecting 5 x 10(4)
      microspheres to 361 mm Hg.ml(-1).s(-1) +/- 158 mm Hg.ml(-1).s(-1) at the dosage
      of injecting 10 x 10(4) microspheres (P < 0.05). The min-CR value remained almost
      unchanged from the dosage of 10 x 10(4) to 15 x 10(4) microspheres. There was no
      significant difference concerning the first-harmonic min-CR between the value at
      the dosage of 5 x 10(4) microspheres and that before microembolization. Along
      with the increase of number of microspheres injected the min-CR value increased
      gradually. The min-CR value was increased significantly than that before
      microembolization since the number of microspheres injected surpassed 14 x 10(4).
      CONCLUSION: The first-harmonic min-CR reflected the coronary microvascular
      dysfunction in different extents of microembolization better than min-CR. The
      extent of coronary microvascular dysfunction wasn't linearly related to the
      extent of microembolization.

PMID- 15144595
TI  - [Effects of selective cyclooxygenase-2 inhibitor NS-398 on 5-fluorouracil
      chemotherapy and progression of colon cells: an experimental study].
AB  - OBJECTIVE: To investigate the effects of selective cyclooxygenase-2 (COX-2)
      inhibitor NS-398 on 5-fluorouracil (5-Fu) chemotherapy and on the progression of
      colon cells. METHODS: Colon cancer cells of HT-29 and SW480 lines were cultured.
      Selective COX-2 inhibitor NS-398, 5-Fu, or NS-398 combining with 5-Fu were added
      into the cultures to be co-cultured for 24, 48, and 72 hours respectively. RT-PCR
      and ELISA analysis were performed to detect the level of COX-2 mRNA expression
      and prostaglandin 2 (PGE2) concentration in the cells of both HT-29 and SW480
      lines. The proliferation and apoptosis of the two cell lines were observed with
      MTT assay and flow cytometry. RESULTS: Expression of COX-2 mRNA were negative in
      SW480 line and positive in HT-29 line. Compared with SW480 line, the HT-29 line
      showed an obvious decline of PGE2 concentration following NS-398 treatment. Both
      NS-398 and 5-Fu inhibited the cells' proliferation and induced apoptosis in a
      dose-dependent manner, and a more significant inhibition was found when the cells
      were co-treated with NS-398 and 5-Fu. Although, there was no significant
      difference between these in inducing apoptosis. CONCLUSION: Selective COX-2
      inhibitor NS-398 can inhibit the proliferation of colon cancer cells and induce
      apoptosis thereof. The mechanism of NS-398 against colon cancer may be
      independent upon the expression levels of COX-2 mRNA and PGE2 of colon cancer. NS
      398 may be a subsidiary drug in 5-Fu chemotherapy in treating colon cancer.

PMID- 15144597
TI  - [Effect of different angiotensin converting enzyme inhibitors on coronary
      collateral circulation].
AB  - OBJECTIVE: To observe the effects of different angiotensin converting enzyme
      inhibitors (ACEI) on coronary collateral circulation. METHODS: Twenty-four
      healthy dogs underwent measurement of distolic aortic pressure (DAP) and ligation
      of the left anterior descending coronary artery. The distolic coronary pressure
      (DCP) and retrograde blood flow (Qret) were measured. Five days after the
      operation the dogs were randomly divided into three groups of 8 dogs: benazepril
      group (benazepril 10 mg qd); captopril group (captopril 12.5 mg bid) and control
      group (starch tablet was given). Thirty days after the operation a reflux
      catheter was inserted to measure the DCP and Qret again. Then the dogs were
      killed and their hearts were taken out to examine the pathologic changes. The
      angiotensin converting enzyme (ACE) activity levels in plasma and myocardium were
      examined by FAPGG spectrophotometry. RESULTS: (1) In the captopril group the
      plasma ACE activity was (24.1 +/- 0.6) U/L 10 days after medication, and 24.3 +/-
      0.6 U/L twenty-five days after medication, both significantly lower than that
      before medication [(57.6 +/- 0.8) U/L, both P < 0.01]; in benazepril group the
      plasma ACE activity was (24.4 +/- 0.4) U/L ten days after medication, and (24.0
      +/- 0.5) U/L 25 days after medication, both significantly lower than that before
      medication [(59.5 +/- 1.3) U/L, both P < 0.01]. The plasma ACE activity levels of
      captopril and benazepril groups, especially of the benazepril group, after
      medication were significantly lower than that of the control group. The tissue
      ACE activity levels of the captopril and benazepril groups were lower than that
      of the control group. (2) The values of DCP in the control and captopril group
      were higher after medication than before medication. A tendency of decrease of
      DCP was shown in the benazepril group, however, without statistical significance.
      (3) In the control group Qcol was (2.01 +/- 0.31) ml/min 25 days after
      medication, significantly than that before medication [(0.91 +/- 0.15) ml/min],
      the corresponding values in captopril group were (2.24 +/- 0.46) ml/min and (0.88
      +/- 0.13) ml/min respectively in the captopril group and (3.18 +/- 0.27) ml/min
      and (0.89 +/- 0.11) ml/min respectively in the benazepril group with the value 25
      days after in the benazepril group being the highest. (4) 30 days after operation
      collateral circulation was established in the ischemic myocardium in all 3
      groups. The microvessel density in the ischemic zone of myocardium was higher
      than that in the nonischemic zone in all 3 groups. The microvessel density in the
      ischemic zone of myocardium was greater in the benazepril group than in the
      captopril and control groups. There was no difference in microvessel density
      between the captopril group and control group. CONCLUSION: Benazepril increases
      the microvessel density and collateral flow, promotes the creation of collateral
      circulation in ischemic area, but captopril has not such effects.

PMID- 15144596
TI  - [Effects of anti-sense Smad4 gene on the biological characteristics of the fat
      storing cell line CFSC].
AB  - OBJECTIVE: To investigate the effects of antisense Smad(4) on the biological
      characteristics of the fat-storing cell line CFSC. METHODS: Fat-storing cells of
      line CFSC from rat with liver fibrosis were cultured and transfected with 50 MOI
      of recombinant adenoviral vector carrying antisense Smad(4) (AdvATSmad(4)) or the
      control empty adenovirus (Adv0), both produced by 293 packaging cells,
      respectively. Two, four, and six days after the transfection the cultured cells
      were collected to undergo trypan blue staining and cell counting. The growth
      curves were drawn. The presence of antisense Smad(4) was detected by RT-PCR and
      Western blotting. (3)H-TdR was added into the culture media to be co-cultured for
      6 hours. Then the cells were collected to examine the (3)H-TdR incorporation
      rate. RT-PCR and immunohistochemistry were used to examine the expression of
      COL1A1 and type I collagen, kinds of extracellular matrix (ECM). RESULTS:
      Compared with the control CFSC and the Adv0-transfected CFSC cells, the cell
      growth curve, (3)H-TdR incorporation rate, proline incorporation rate, expression
      of Smad(4), and expression of extracellular matrix were markedly decreased in the
      AdvATSmad(4)-transfected CFSCs. CONCLUSION: The antisense Smad(4) gene inhibits
      the expression of Smad(4) mRNA and protein, proline incorporation and cell
      growth, thus down-regulating the production of ECM. Antisense Smad(4) gene may be
      used as a choice of gene therapy for liver fibrosis.

PMID- 15144598
TI  - [A new method of pulmonary artery cannulation with minimally invasive
      decannulation for right ventricular assistance:an animal experiment].
AB  - OBJECTIVE: To create a new method of pulmonary artery cannulation during
      operation for right ventricular assistance, for which minimally invasive
      decannulation can be done after operation. METHODS: A specially-made
      disassemblable composite graft consisting of a woven dacron tube and a bovine
      pericardial tube (composite graft) was anastomosed to the pulmonary artery as a
      pathway in seven dogs by median sternotomy. The end of the woven dacron tube and
      a link-thread for connecting the two tubes in the composite graft were drawn
      outside the body through an intercostal tunnel. A predisposed drawing-tieing
      thread in the composite graft was drawn outside through another intercostal
      tunnel and then tightened. An inflow cannula was placed into the left femoral
      vein or jugular vein via an incision of skin so as to establish a right
      ventricular assist system. By means of the centrifugal pump, the right
      ventricular bypass was established. After stopping the pumping, the 2 sets of
      predisposed prolene thread in the composite graft were tied by catheter and
      knotting tool via the small skin incision, 8 knots for each set, to close the
      bovine pericardial tube, and then the drawing-tieing thread, link-thread, and the
      dacron tube in the composite graft were removed. Median sternotomy was performed
      again to observe the anastomotic stoma, the closure of the stump of bovine
      pericardial tube, and whether hemorrhage occurred. RESULTS: The mean maximum
      output of right ventricular assist system from left femoral or jugular vein to
      pulmonary artery was (64.4 +/- 12.3) ml.min(-1).kg(-1). The second sternotomy
      showed satisfactory knotting on the bovine pericardial tube except in one case,
      whose second set of drawing-tieing thread was tied in the seventh knot and failed
      to be drawn out, thus partially remained in the body. No bleeding was found in
      all cases. CONCLUSION: The new cannulating methods with minimally invasive
      decannulation after operation created in this study is simple, easy and
      effective.

PMID- 15144606
TI  - [Taking precautions, strengthen the prevention and management of avian influenza
      in human beings].

PMID- 15144607
TI  - [Effect of protein kinase C-nuclear factor-kappa B signal transduction pathway on
      proliferation and expression of vascular endothelial growth factor in human
      pulmonary artery smooth muscle cells].
AB  - OBJECTIVE: To investigate the effect of protein kinase C (PKC)-nuclear factor
      kappa B (NF-kappaB) signal transduction pathway on proliferation and expression
      of vascular endothelial growth factor (VEGF) in human pulmonary artery smooth
      muscle cells (HPASMCs). METHODS: Cultured HPASMCs in normoxia or hypoxia
      conditions were divided into three groups and stimulated with or without phorbol
      12-myristate 13-acetate (PMA) and pyrrolidine dithiocarbamate (PDTC) in vitro.
      The three groups were the control group, the PMA group and the PMA + PDTC group.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect VEGF
      mRNA expression, and the expression of VEGF protein and the inhibitor protein
      IkappaBalpha were observed by Western blot, while the location and expression of
      NF-kappaB p65 were observed by immunocytochemical staining, and cell cycle phases
      were analyzed by flow cytometry. RESULTS: (1) As for the positive rate of
      nucleolar staining for NF-kappaB p65, the relative expression of IkappaBalpha
      protein, and the percentage of G(2)/M phases of cell cycle, there were
      significant differences between the PMA group and the control group or PMA + PDTC
      group, both in normoxia and hypoxia conditions (P < 0.05, respectively), and
      there was also a significant difference between the normoxia and hypoxia PMA
      groups (P < 0.05). (2) There were no significant differences in VEGF mRNA and
      protein expression among the three groups (P > 0.05, respectively) in normoxia,
      but the expression was higher in hypoxia PMA group than in hypoxia control and
      hypoxia PMA + PDTC or normoxia PMA group (P < 0.05, respectively). (3) There was
      a positive correlation between the positive rate of nucleolar staining for NF
      kappaB p65, the relative expression of VEGF protein and the percentage of G(2)/M
      phases of cell cycle in hypoxia PMA group (r = 0.587 - 0.710, P < 0.05,
      respectively). CONCLUSIONS: There is a signal transduction pathway of PKC-NF
      kappaB in HPASMCs. The activity of PKC can be enhanced in hypoxia, concomitant NF
      kappaB activation or VEGF overexpression to be involved in the proliferation.
      These results suggest that the activation of NF-kappaB can be considered as a
      downstream of PKC signal transduction pathway, and the activation of PKC-NF
      kappaB signal transduction pathway and VEGF overexpression may contribute to the
      process of hypoxic pulmonary hypertension.

PMID- 15144609
TI  - [The temporal and spatial distribution of vasoactive intestinal peptide and its
      receptor in the development of airway hyperresponsiveness].
AB  - OBJECTIVE: To determine the possible involvement of vasoactive intestinal peptide
      (VIP) in the development of airway hyper responsiveness (AHR). METHODS: Twenty
      five rabbits were randomly divided into five groups (5 animals each). Four groups
      were exposed to 2.0 ppm ozone 1 h/day for 1 (group B(0)), 2 (group B(1)), 4
      (group B(2)), and 8 (group B(3)) days, respectively. The control group (group A)
      breathed only filtered room air. The changes of the VIP level and the mRNA
      expression of VIP receptor 1 (VIPR1) in the lung were detected at various ozone
      stressing time points. In situ hybridization was performed to examine the
      distribution of VIPR1 in the lung. RESULTS: (1) The concentration of VIP in the
      lung increased slowly and were maximal at day 4, then returned to the normal
      level. (2) The changing pattern of the VIPR1 mRNA in the lung was similar to
      those observed for VIP. Increases in VIPR1 mRNA were detectable by 1 day and
      maximal by 2 - 4 days, and then decreased slowly. (3) In group A, VIPR1 was
      expressed on airway epithelium, in pulmonary interstitial and focal areas of
      airways and vascular smooth muscles. By days 2 to 4, hybridization staining
      increased and the majority of VIPR1-positive cells was located in the
      perivascular and peribronchiolar area. On day 8, very few positive cells were
      seen in the lung. CONCLUSION: VIP may play an important role in the development
      of AHR by binding with VIPR1.

PMID- 15144612
TI  - [An experimental study of the therapeutic effect of interleukin-2 and interleukin
      12 with and without amphotericin B on pulmonary fungal infection].
AB  - OBJECTIVE: To study the therapeutic effect of interleukin-2 (IL-2) and
      interleukin-12 (IL-12) with and without amphotericin B on pulmonary fungal
      infection of mice. METHODS: A mouse model of pulmonary invasive aspergillus
      fumigatus (IPA) infection was established and the mice were divided into
      different groups, treated with IL-2 and IL-12 with and without amphotericin B.
      The survival number of mice in 15 days and the colony count of lung tissue in the
      different groups were observed. RESULTS: IL-2, IL-12 and amphotericin B showed
      synergistic effect in prolonging the survival of the infected mice and reducing
      the colony count in the lung tissue. CONCLUSION: IL-2 and IL-12 are effective
      adjuvant therapeutic agents in the immunosuppressed hosts.

PMID- 15144611
TI  - [The effects of anti-inflammatory and anti-asthmatic agents on CD34+
      hematopoietic cells in bone marrow of asthmatic mice].
AB  - OBJECTIVE: To observe the effects of glucocorticoids and cysteinyl leukotrienes 1
      receptor antagonist on CD(34)(+) hematopoietic cells, and to study the
      rationality of a bone marrow-targeting anti-inflammatory strategy. METHODS:
      Twenty-four BALB/c mice were sensitized and challenged by 1% ovalbumin (OVA) to
      establish the asthmatic model. Asthmatic mice were challenged by 1% OVA and
      divided into 4 groups: fed by sterile saline (group A), prednisone (group B),
      montelukast (group C) and prednisone plus montelukast (group D) respectively for
      two consecutive weeks. The mice were killed at 24 h after the last challenge,
      then bronchoalveolar lavage fluid (BALF), peripheral blood and bone marrow were
      prepared. Eosinophils in peripheral blood and BALF, nucleate cells in BALF,
      peripheral blood and bone marrow were counted. The percentage of CD(34)(+) cells,
      CD(4)(+), CD(8)(+) T lymphocyte to nucleate cells in peripheral blood and bone
      marrow were counted by flow cytometry. Immunocytochemistry and in situ
      hybridization were employed to detect the hematopoietic cells expression of
      CD(34)(+) and IL-5Ralpha mRNA in bone marrow (CD(34)(+) IL-5Ralpha mRNA(+)
      cells). RESULTS: The number of EOS in BALF and peripheral blood and the number of
      CD(34)(+) cells in peripheral blood and bone marrow in group A were [(18.3 +/-
      1.3) x 10(5)/L], [(2.5 +/- 0.4) x 10(8)/L], [(9.6 +/- 5.1) x 10(7)/L] and [(7.7
      +/- 3.2) x 10(7)/femur] respectively, compared with the corresponding indices in
      group B [(4.6 +/- 1.7) x 10(5)/L, (1.5 +/- 0.3) x 10(8)/L, (3.9 +/- 2.1) x
      10(7)/L, (3.3 +/- 1.8) x 10(7)/femur] and group D [(3.7 +/- 1.4) x 10(5)/L, (1.7
      +/- 0.3) x 10(8)/L, (4.1 +/- 1.8) x 10(7)/L, (2.2 +/- 0.7) x 10(7)/femur]; the
      differences all were significant (all P < 0.01). The number of bone marrow
      CD(34)(+) IL-5Ralpha mRNA(+) in group B and D were (23 +/- 7)% and (21 +/- 4)%,
      as compared with the corresponding index in group A [(37 +/- 4)%], the
      differences were significant (P < 0.01); the number of eosinophils in BALF in
      group C was (12.2 +/- 1.1) x 10(5)/L, as compared with the corresponding index in
      group A [(18.3 +/- 1.3) x 10(5)/L], the difference was significant (P < 0.05).
      CONCLUSIONS: Prednisone probably inhibits the proliferation, differentiation and
      emigration of CD(34)(+) cells in the bone marrow of asthmatic mice, and inhibits
      eosinophilopoiesis in bone marrow, eosinophil migration into peripheral blood and
      recruitment to the airways. Montelukast may suppress eosinophil infiltrating into
      lungs of asthmatic mice, but it does not inhibit the proliferation and emigration
      of CD(34)(+) cells and does not show apparent synergistic effect with prednisone.

PMID- 15144613
TI  - [Concurrent radiotherapy combined with carboplatin and etoposide in limited stage
      small cell lung cancer].
AB  - OBJECTIVE: To observe the effect of concurrent radiotherapy combined with
      carboplatin and etoposide in limited stage small cell lung cancer. METHODS:
      Ninety patients with limited stage small cell lung cancer were randomized into
      two groups, concurrent treatment group (group A) and sequential treatment group
      (group B). All the patients in two groups received radiotherapy (60 Gy in 6
      weeks) and six courses of chemotherapy (carboplatin and etoposide). Radiotherapy
      was started in the first course of chemotherapy in group A. Patients of group B
      were treated by radiation between the fourth and the fifth course of
      chemotherapy. RESULTS: The median survival time was 26 months in group A and 19
      months in group B. The 5-year survival rate was 27% in group A and 16% in group
      B. The major toxic reactions were grade III-IV myelosuppression. The differences
      of two groups were significant (P < 0.05). CONCLUSION: Concurrent radiotherapy
      combined with carboplatin and etoposide can significantly improve median survival
      time and 5-year survival rate of patients with limited stage small cell lung
      cancer.

PMID- 15144614
TI  - [Oncostatin M gene therapy in mice bearing lung adenocarcinoma xenograft using a
      hypoxia/radiation dual-sensitive promoter].
AB  - OBJECTIVE: To improve the efficacy of radiogenetic therapy for lung cancer, a
      hypoxia/radiation dual-sensitive promoter was constructed to enhance the
      expression of oncostatin M (OSM) in transfected cells exposed to radiation under
      hypoxia. METHODS: The chimeric promoter HRE-Egr was generated by insertion of
      hypoxia response elements (HREs) upstream of the Early growth response gene-1
      (Egr-1) promoter. OSM expression vector was constructed by cloning HRE-Egr
      promoter upstream of OSM gene, which was transfected into A549 cells. The
      expression of OSM in transfected cells exposed to irradiation and(or) hypoxia was
      analyzed, and the relative survival rate of transfected cells exposed to the
      above conditions was tested. To examine the efficacy of this HRE-Egr-OSM gene
      therapy in vivo, the tumor suppression effects were investigated in 40 nude mice
      bearing lung adenocarcinoma xenograft. RESULTS: Expression of OSM gene in
      transfected cells exposed 6 Gy irradiation was markedly increased under hypoxia.
      A gene therapy experiment in vitro showed that the survival rate of transfected
      cells exposed to radiation under hypoxia was obviously decreased with comparison
      of cells under normoxia. HRE-Egr promoter transfected tumors regressed
      significantly after a combination therapy of irradiation and HRE-Egr transfection
      in all mice (n = 10), and six tumors disappeared in 3 weeks without any side
      effects. CONCLUSION: The data indicate that tumor targeted expression of OSM gene
      under the control of a hypoxia/radiation dual-sensitive promoter represents a
      novel strategy for safe and effective gene therapy of lung carcinoma and might
      have clinical application in the future.

PMID- 15144615
TI  - [Preparation and application of recombinant Mycobacterium tuberculosis CFP10-ESAT
      6 fusion protein].
AB  - OBJECTIVE: To prepare the recombinant CFP10-ESAT-6 fusion protein, and to study
      its immunological characteristics, and its potential for serodiagnosis of
      tuberculosis. METHODS: The lhp-ESAT-6 fusion gene was amplified by Gene SOEing,
      and then cloned into pQE30 plasmid. The recombinant CFP10-ESAT-6 fusion protein
      was expressed and purified. Its antigenicity was confirmed by Western blot.
      Animal models infected with M. tuberculosis H(37)Rv strain and M. bovis BCG
      respectively were made to evaluate the potential value of the fusion protein in
      the serodiagnosis of tuberculosis. RESULTS: The sequence of recombinant plasmid
      pQE30-CFP10-ESAT-6 was identical to the predicted sequence. The recombinant
      protein (rCFP10-ESAT-6), about 26 000, existed in the cytoplasm of DH5alpha in
      soluble form and represented 40% of the total bacterial protein. The purity and
      concentration of the final product was 98% and 1.2 g/L, respectively. Western
      blot showed that the rCFP10-ESAT-6 had good immunoreactivity with sera from
      patients with active tuberculosis and rabbits immunized with CFP10 and ESAT-6
      respectively. The positive cutoff value was A(490) plus 2 standard deviation from
      negative guinea pig sera detected by ELISA. Serological reactivity to rCFP10-ESAT
      6 was observed in 11 of the serum samples from guinea pigs with tuberculosis and
      1 of sera from guinea pigs infected with BCG, while the serological reactivity to
      PPD was observed in 11 of sera from guinea pigs with tuberculosis and in 11 of
      sera from guinea pigs infected with BCG. CONCLUSIONS: The rCFP10-ESAT-6 fusion
      protein was highly expressed in soluble form in E. coli. It had antigenicity of
      both CFP10 and ESAT-6, and could be used to differentiate infection with M.
      tuberculosis H(37)Rv strain from immunization with M. bovis BCG. The study
      provided experimental data for potential application of rCFP10-ESAT-6 in the
      diagnosis of tuberculosis.

PMID- 15144616
TI  - [Constructing shuttle plasmid fusion expressing Ag85B-ESAT-6 on the surface of
      Mycobacterium].
AB  - OBJECTIVE: To construct the E. coli.-BCG (Bacille Calmette-Guerin) shuttle vector
      expressing Mycobacterium tuberculosis secreted protein Ag85B-ESAT-6 on the
      surface of Mycobacterium vaccae. METHODS: The gene fragment containing 19 000
      antigen (19-ss) were amplified by polymerase chain reaction (PCR) from the
      Mycobacterium tuberculosis H(37)Ra. We cloned the 19ss gene into the E. coli.-BCG
      shuttle vector pOLYG and named the pCW, which can shuttle and express exogenous
      antigen gene on cell wall of Mycobacterium. Then Mycobacterium tuberculosis
      secret protein Ag85B and ESAT-6 gene were cloned into the vector and determined
      by indirect immunofluorescence. RESULTS: The sequence of 19-ss gene was
      identified with Genbank reported by sequencing. The constructed E. coli.-BCG
      shuttle vector using 19ss gene had the function of shuttle between E. coli. and
      Mycobacteria. By indirect immunofluorescence technique the secreted protein Ag85B
      ESAT-6 can be fused and expressed on surface of Mycobacterium vaccae. CONCLUSION:
      The E. coli.-BCG shuttle vector is constructed successfully which could express
      exogenous antigen gene as a chimeric exported membrane.

PMID- 15144618
TI  - [Pulmonary edema caused by ventilator-associated lung injury].

PMID- 15144619
TI  - [Structural and functional aspects of influenza virus RNA polymerase].

PMID- 15144637
TI  - [Experience on transplantation of auto-pulmonary graft treating with congenital
      aortic disease].
AB  - OBJECTIVE: To summarize the experience on auto-pulmonary transplantation (Ross
      procedure) treating with congenital aortic disease. METHODS: From October 1994 to
      November 2003, 20 cases of Ross procedure were performed to treat with congenital
      aortic disease, Male: 15 cases; Female: 5 cases; age: 25 years; DIAGNOSIS:
      congenital heart disease (CHD), aortic abnormalities: 12 cases; aortic valve
      prolapse: 5 cases; aortic valve hypogenesis: 3 cases; combined with subacute
      bacterial endocarditis (SBE): 4 cases, and ventricle septal defect (VSD): 2
      cases; UCG showed aortic stenosis(AS) and/or aortic insufficience (AI) (moderate
      to severe), Left ventricle diastole diameter (LVDD): (60.51 +/- 11.87) mm, the
      grade pressure across aortic valve: (27.04 +/- 6.80) mmHg, heart function (NYHA):
      Class II: 13 cases; Class III: 3 cases; all cases were performed under CPB and
      moderate hypothermia, the operation procedure was following: (1) taking off auto
      pulmonary artery valve; (2) removing dysfunctional aortic valve and auto
      transplantation of pulmonary valve on aortic root; (3) putting a pulmonary
      homograft to rebuild right ventricular outflow tract. RESULTS: The mortality was
      0 during stay at hospital, aortic valve function were all normal, LVDD decreased
      significantly (t = 3.4007, P = 0.0008), the grade pressure across aortic valve
      was in normal limitation, (6.8 +/- 0.19) mmHg. Follow-up showed heart function
      was in Class I (NYHA), aortic and pulmonary valve function was very well.
      CONCLUSION: Ross procedure is a kind of effective alterative operation for
      treating with congenital aortic valve disease, with good short and middle term
      results.

PMID- 15144636
TI  - [Arterial switch operation for transposition of the great arteries and double
      outlet of right ventricle with subpulmonary ventricular septum defect].
AB  - OBJECTIVE: To summarize the clinical experience on the arterial switch operation
      for complex congenital heart disease in recent 3 years in our hospital. METHODS:
      Sixty-one patients with complex congenital heart disease received by arterial
      switch operation from Jan 2000 to May 2003. There were 26 patients with
      transposition of the great arteries and intact ventricular septum (TGA-IVS), 19
      patients with transposition of the great arteries and ventricular septal defect
      (TGA-VSD) and 16 patients with double outlet of right ventricle with subpulmonary
      ventricular septum defect (Taussig-Bing). RESULTS: There were 2 death among TGA
      IVS cases, 4 deaths among TGA-VSD cases and 4 deaths among Taussig-Bing cases.
      The total operative mortality was 16%. All patients were followed up 3 months to
      3 years. In all patients, the cyanosis disappeared and the physical activities
      increased obviously. One patients with Taussig-Bing keep moderate mitral valve
      reflux unchanged, 2 patients with TGA had pulmonary and aortic supra-valve
      stenosis with 40 mmHg pressure gradient. One patient with subpulmonary stenosis
      and residual VSD was re-operated 3 months later. All survivor had good heart
      function. CONCLUSIONS: The effect of arterial switch operation on the treatment
      of TGA was well accepted in this study. The procedure used in treatment on
      Taussig-Bing can prevent pulmonary obstruction and avoid the complication of left
      ventricular outflow tract obstruction caused by intraventricular repair.

PMID- 15144639
TI  - [Surgical treatment on residual shunt after repair of ventricular septal defect].
AB  - OBJECTIVE: To summarize the experience in surgical treatment of residual shunt
      after repair of ventricular septal defect and investigate the position of the
      residual shunts. METHODS: Between January 1979 and May 2003, re-operations on
      residual shunt after repair of ventricular septal defect were performed in 37
      patients with congenital heart disease including ventricular septal defect,
      tetralogy of Fallot, double outlet right ventricle in 19, 17 and 1 patients,
      respectively. It accounted for 0.21% (37/18000) of open heart operations
      performed during these years. The patients included 26 males and 11 females with
      age from 3 months to 53 years (mean 16 +/- 12 years). The residual shunt was
      diagnosed by postoperative murmur and echocardiography. Twenty-six cases were
      repaired with patch and 11 cases were closed directly with mattresses sutures.
      RESULTS: Two patients (2/37, 5%) died within 48 hrs postoperatively. The results
      in other 35 patients followed up after surgery from 3 months to 15 years were
      satisfactory. CONCLUSIONS: Most of the residual shunts occurred in base of septal
      leaflet of tricuspid valve, the second and the first transfer suture
      respectively. Effects of reoperations on residual shunts were satisfactory.

PMID- 15144638
TI  - [Fontan operation with extracardiac conduit on beating hearts].
AB  - OBJECTIVE: To evaluate the results of Fontan operation with extracardiac conduit
      on beating hearts. METHODS: Forty-two patients (31 males and 11 females) age
      ranged from 3 to 19 years old included in this study. There were 19 double inlet
      ventricle, 10 tricuspid atresia, and 3 patients with mitral atresia, 10 patients
      with other complex congenital cardiac malformations. Fontan operations with
      extracardiac conduit were performed in all patients with the help of
      cardiopulmonary bypass without hypothermia in this study. Atrial septal
      fenestration was performed in 8 patients. In one patient, bi-directional
      cardiopulmonary procedure was performed 2 years before Fontan operation. RESULTS:
      There was one early death caused by acute hepatic function failure and one late
      death caused by repeated lung infections. The follow-up of 1 to 4.5 years showed
      that all patients' cardiac functions were grade I to II, and arterial oxygen
      saturation was 92% - 96%. CONCLUSIONS: The early and mid-term outcome of Fontan
      operation with extracardiac conduit on beating hearts is good and the method can
      be used in the single ventricle repair.

PMID- 15144640
TI  - [Anatomical and clinical study of the supinator syndrome evoked embitterment
      test].
AB  - OBJECTIVE: To explore the mechanism and feasibility of the supinator syndrome
      evoked embitterment test from anatomy and clinic. METHODS: 25 cases of The
      supinator syndrome were reviewed. 18 of them were male and 7 were female. Drop
      finger deformation were apparent in 25 cases and The supinator syndrome evoked
      embitterment test was positive for All patients. Operative neurolysis was done in
      8 cases, conservation treatment 17 cases; 92 cadaver upper extremities were
      dissected for a study the relationship between supinator tunnel and posterior
      interosseous nerve. RESULTS: 22 cases had been followed up for an average of 9
      months. 16 cases had a full recovery and 6 cases, a partial recovery. the
      anatomical study shows that The posterior interosseous nerve was compressed by
      Forhse arcade and the distal border of the supinator muscle during passive
      pronation forearm. CONCLUSION: The supinator syndrome evoked embitterment test
      was a new test for the diagnosis of supinator syndrome, it was found to be more
      sensitive and specific than the others test.

PMID- 15144641
TI  - [Instability of C1,2 treated with transcutaneous anterior lateral mass fixation
      and bone grafting].
AB  - OBJECTIVE: Creating the method of transcutaneous anterior lateral mass fixation
      for instability of C(1,2). METHODS: The regular and safe angle and the distance
      between the median margin of vertebral artery and median line of superior and
      inferior margin of axis were measured with computerized tomography. Fifteen cases
      of C(1,2) instability including 7 cases atlanto-axial dislocation, 3 cases of
      Jefferson's fracture, 1 case of dental fracture and dislocation and 4 cases of
      fractures of anterior arch of C1 were treated with pertacuneous anterior lateral
      mass screws and bone grafting with new-designed hole instrumentations according
      to the measurement of 40 normal atlanto-axial vertebrae. RESULTS: In posterior
      anterior ray the regular angle was 24.0 degrees +/- 3.7 degrees (right side), and
      23.8 degrees +/- 1.8 degrees (left side); safe angle is 15.2 degrees - 30.3
      degrees (left side) and 14.8 degrees - 32.1 degrees (right side), respectively.
      The distance between the median margin of vertebral artery and median line of
      superior and inferior margin of vertebral artery and median line of superior and
      inferior margin of lateral mass was (5.6 +/- 2.2) mm (right) and (5.8 +/- 1.9) mm
      (left). In lateral ray the regular angle was 24.1 degrees +/- 1.8 degrees, and
      safe angle 12.6 degrees - 26.8 degrees. All cases reach a satisfactory result of
      fixation without the injury of vertebral artery, spinal cord and esophagus. The
      acupuncture point recovers without infection. CONCLUSIONS: This operation
      procedure for instability of C(1,2) has the advantage of less trauma and
      bleeding, simply operation and bone grafting at the same time. The operation
      procedure is safe with reasonable instrument and selecting the correct puncture
      point, angle and depth.

PMID- 15144642
TI  - [A long-term follow-up study of high tibial osteotomy in medial compartment
      osteoarthrosis].
AB  - OBJECTIVE: To observe long-term outcome of high tibial osteotomy (HTO) in
      treating the medial compartment osteoarthrosis of the knee. METHODS: A
      retrospective study was made between 1985 and 1996, of 194 patients (215 knees)
      who had HTO in medial compartment osteoarthritis at the Orthopaedic Hospital of
      Kiel University. RESULTS: One hundred and sixty-one knees were reviewed at an
      average follow-up of 7.5 years (range, 1.5 - 12 years). 97.3% good and excellent
      results up to two years postoperatively; 93.6% good and excellent results up to
      five years postoperatively; at over five years, 78.2% good and excellent.
      Nineteen (11.8%) knees had required conversion of their HTO to a total knee
      arthroplasty (TKA). The survive rate of HTO taking as TKA as an end point is
      98.7% in 2 years; 95.0%, 5 years and 84.1%, 10 years. CONCLUSIONS: We believe
      that the high tibial osteotomy is one of good methods in treating the medial
      compartment osteoarthritis of the knee, overcorrection the femorotibial alignment
      is the key step of the operation. Postoperatively, there is a trend of the
      results to get worse with time and a part of the patients had been revised to
      total knee arthroplasty because of a poor result.

PMID- 15144643
TI  - [The significance of platelet-derived endothelial cell growth factor mRNA
      expression in superficial bladder cancer].
AB  - OBJECTIVE: To investigate the mRNA expression of platelet-derived endothelial
      cell growth factor (PD-ECGF) in superficial bladder cancer and its significance.
      METHODS: PD-ECGF mRNA expressions were determined by RT-PCR in 28 cases of
      superficial bladder cancers and 6 cases of normal bladder mucosa. The relation
      between PD-ECGF mRNA expression and tumor invasion to lamina propria or
      recurrence after transurethral resection was also analyzed. RESULTS: Some degree
      of PD-ECGF mRNA expression was present in all the samples. The PD-ECGF mRNA level
      was 3.1-fold higher in pT(1) tumors than in normal bladder mucosa (t = 2.13, P <
      0.05) and 2.2-fold higher in pT(1) tumors than in pT(a) tumors (t = 2.66, P <
      0.05); G(3) tumors expressed 3.3-fold higher PD-ECGF mRNA than normal bladder
      mucosa (t = 2.44, P < 0.05) and 2.5-fold higher than G(1 - 2) tumors (t = 3.36, P
      < 0.01). Eleven cases recurred during the mean follow-up period of 18 months.
      Three-fold higher PD-ECGF mRNA expression was showed in cases who recurred after
      transurethral resection than that in cases who did not recur (t = 4.49, P <
      0.01). The specificity and sensitivity of predicting tumor recurrence were 82.4%
      and 81.8% respectively using 0.095 as a cutoff value of PD-ECGF mRNA level in
      this group of superficial bladder cancer. CONCLUSION: PD-ECGF mRNA expression
      correlates with tumor dedifferentiation and plays an important role in the early
      invasion in superficial bladder cancer. To analyze the PD-ECGF mRNA level
      contributes to the evaluations of tumor differentiation and invasion to lamina
      propria as well as recurrence prediction in superficial bladder cancer.

PMID- 15144645
TI  - [Clinical investigation of renal angiomyolipoma].
AB  - OBJECTIVE: To study the diagnosis and management of renal angiomyolipoma (RAML),
      and to identify risk factors affecting spontaneous angiomyolipoma rupture.
      METHODS: The data of 68 patients with RAML from 1989 to 2002 were retrospectively
      reviewed. These patients were divided in two groups on the basis of tumor size,
      35 patients in group A (<or= 4 cm) and 33 patients in group B (> 4 cm). RESULTS:
      Seven patients were identified by image-guided percutaneous biopsy, and no major
      complications was noted. Sixteen patients with RAML were examined with
      angiography and 9 of 16 patients had got spontaneous rupture. 41.2% of patients
      were symptomatic, 4 cases (11.4%) in group A and 24 (72.7%) cases in group B (P <
      0.01). There were significant differences in mean tumor size (11.6 cm +/- 5.1 cm
      vs 5.3 cm +/- 2.9 cm, P < 0.01) and mean aneurysm size (13.6 mm +/- 5.8 mm vs 2.6
      mm +/- 3.0 mm, P < 0.01) between 9 cases of the ruptured tumor and 59 cases of
      unruptured tumor, 9 cases of the ruptured and 7 cases of unruptured tumor with
      angiography, respectively. Treatment consisted of conservative observation in 10
      patients (no radiographic changes during the follow-up of 2 - 7 years); partial
      nephrectomy in 14 patients, tumor enucleation in 30 patients, total nephrectomy
      in 14 and posterior laparoscopic nephrectomy in 3 (no recurrence and complication
      correlation to operation during the follow-up of 2 - 144 months). CONCLUSIONS: It
      is an important role that percutaneous biopsy guided by ultrasonography or
      computerized tomography performs in managing suspicious and/or indeterminate
      RAML. A higher probability of rupture is related to tumor and/or aneurysms size.
      Nephron-sparing surgery is the first choice for surgical treatment of RAML.

PMID- 15144646
TI  - [Effects on neuronal ultrastructure and nervous system of monkey after selective
      cerebral profound hypothermia and blood flow occlusion].
AB  - OBJECTIVE: To study the effects of deep hypothermia on the neuronal
      ultrastructure and nervous system of monkey after selective cerebral profound
      hypothermia and blood flow occlusion. METHODS: Brain-local extracorporeal
      circulation was established by right internal carotid artery deep hypothermic
      perfusion and homolateral external jugular vein backflow, brain blood flow was
      recovered from circulatory arrest 60 - 80 minutes late and monkey came back
      naturally. RESULTS: In all 7 monkeys, 5 were succeeded in being build up the
      models except for 2 because of technic problems, and 4 of them lived up for ever.
      The function of nervous system grade, essential organ and neuronal ultrastructure
      were normal. CONCLUSION: Selective cerebral profound hypothermia can increase the
      ability of brain to endure hypovolemia and hypoxidosis and prolong the time of
      blood flow occlusion.

PMID- 15144664
TI  - [Effects of extracellular signal-regulated kinase inhibition by AG126 on tissue
      tumor necrosis factor-alpha expression and multiple organ dysfunction in rats
      with postburn Staphylococcus aureus sepsis].
AB  - OBJECTIVE: To investigate the effects of extracellular signal-regulated kinase
      (ERKs) inhibition by AG126 on tissue tumor necrosis factor-alpha (TNF-alpha)
      expression and multiple organ dysfunction in rats with postburn Staphylococcus
      aureus sepsis and its potential signal regulating mechanism. METHODS: To
      reproduce postburn sepsis model, male Wistar rats were inflicated with 20% total
      body surface area third-degree scald followed by Staphylococcus aureus challenge.
      34 rats were randomly divided into four groups as follows: normal control group
      (n = 6), scald control group (n = 6), postburn sepsis group (n = 12), and AG126
      treatment group (n = 10). Tissue samples from the liver, kidneys and lungs were
      collected to determine phosphorylated ERKs by Western blot analysis, and TNF
      alpha mRNA expression as well as its protein levels. RESULTS: It was revealed
      that phosphorylated ERKs in the liver, lungs, and kidneys from postburn septic
      animals were up-regulated rapidly at 0.5 - 2.0 hours, being 1.94-fold (P < 0.05),
      2.86-fold (P < 0.01), and 1.41-fold at 2.0 hours compared to normal controls,
      respectively. Treatment with AG126 could significantly reduce phosphorylated ERKs
      in lung tissue by 70.6% (P < 0.01) at 2.0 hours postburn sepsis, and almost
      completely inhibited ERKs activation in the liver and kidneys at various time
      points. Meanwhile, both TNF-alpha mRNA and protein expressions in the liver,
      lungs, and kidneys were significantly decreased in AG126-treated group following
      septic challenge (P < 0.05 or 0.01). In addition, 2.0 hours after Staphylococcus
      aureus infection, treatment with AG126 markedly improved hepatic and renal
      function parameters, including serum ALT, AST, Cr, as well as BUN levels (P <
      0.05 or 0.01), together with significant decrease in pulmonary myeloperoxidase
      activity, compared to those without AG126 treatment. CONCLUSION: These data
      suggested that ERKs signal transduction might be involved in the pathogenesis of
      systemic inflammatory response and multiple organ dysfunction in postburn gram
      positive bacterial sepsis. Early treatment with AG126 could significantly down
      regulate TNF-alpha mRNA expression as well as protein levels in vital organs and
      attenuate multiple organ dysfunction induced by scald injury combined with
      Staphylococcus aureus challenge.

PMID- 15144663
TI  - [Role of p38 mitogen-activated protein kinase signal transduction pathway in the
      acute lung injury of severely burned rats].
AB  - OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK)
      signal transduction pathway in the acute lung injury of severely burned rats.
      METHODS: Forty-eight adult healthy rats were randomly divided into three groups:
      sham group, burn control group, and burn + SB203580 group. A third-degree burns
      over 30% total body surface area rat model was used and pulmonary capillary
      permeability, lung water content, pulmonary histology and p38 MAPK activity were
      measured at 24 hours postburn. RESULTS: Burn trauma resulted in increased
      pulmonary capillary leakage permeability (42.5 +/- 4.7 vs. 12.1 +/- 1.4, P <
      0.01), elevated lung water content (P < 0.05), and worsen histologic condition.
      There was a significant activation of p38 MAPK at 24 hours postburn compared with
      control. SB203580 inhibited the activation of p38 MAPK, reduced the pulmonary
      capillary leakage permeability (24.7 +/- 2.9 vs. 42.5 +/- 4.7, P < 0.01),
      decreased lung water content, and prevented burn-mediated lung injury.
      CONCLUSION: The activation of p38 MAPK is one important aspect of the signaling
      event that contributes to burn-induced lung injury.

PMID- 15144665
TI  - [Effects of the escharectomy during burn shock stage on expression of glucose
      translator-4 mRNA in skeletal muscle and adipose tissue].
AB  - OBJECTIVE: To investigate the effect of the escharectomy during burn shock stage
      on expression of glucose translator-4 (GLUT4) mRNA in skeletal muscle and adipose
      tissue. METHODS: 30% TBSA scalded rats were employed. Escharectomy were conducted
      at 8 h, 24 h, 168 h after burns respectively. Insulin, glucagon, cortisol and
      glucose levels in serum were analyzed. RT-PCR were employed to analyze GLUT4 mRNA
      expression in skeletal muscle and adipose tissue. RESULTS: Glucagon, cortisol and
      glucose levels in serum were declined in groups which escharectomy were conducted
      during burn shock stage. GLUT4 mRNA expression in both skeletal muscle and
      adipose tissue were downregulated after burns and escharectomy conducted during
      burn shock stage made it restored to near normal. CONCLUSION: GLUT4 mRNA
      expression will declined after major burns in skeletal muscle and adipose tissue.
      Escharectomy during shock stage could make it upregulated, which will be helpful
      to improve glucose metabolism and hypermetabolism after major burns.

PMID- 15144667
TI  - [Effects of glutamine granules on protein metabolism in trauma patients].
AB  - OBJECTIVE: To evaluate the effect of glutamine granules on protein metabolism in
      severe burns and trauma patients. METHODS: 120 patients with severe burns,
      multiple trauma and post operation who met the requirements of the protocol
      joined this double-blind randomized controlled, multi-center clinical trail.
      Patients were randomly divided into two groups: placebo control group (P group,
      60 patients) and glutamine granules treatment group (GLN group, 60 patients).
      There was isonitrogenous and isocaloric intake in both groups, GLN and P group
      patents had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(
      1) for 7 days, respectively. The level of plasma glutamine, protein and urine
      nitrogen exclude were determined, wound healing rate of burn area and hospital
      stay were recorded, and then observed the complication and side effect. RESULTS:
      After 7 days of taking glutamine granules orally, plasma GLN concentration was
      significant higher than that in P group (592.50 +/- 185.23 micro mol/L vs. 407.41
      +/- 190.22 micro mol/L) (P < 0.01). Plasma prealbumin and transferrin in GLN
      group were significant higher than those in P group (P < 0.01), but the
      concentration of total protein and albumin were no marked changes compare with P
      group (P > 0.05). The capacity of urine nitrogen exclude in GLN group were
      significant lower than that in P group. Additional, the wound healing rate was
      faster and hospital stay days was shorter than P group (P < 0.05), and the
      occurrence of glutamine granules side effect was seldom. CONCLUSION: Taking
      glutamine could promote protein synthesis, abate protein decompose, ameliorate
      wound healing rate and reduce hospital stay obviously.

PMID- 15144668
TI  - [The clinical application on composite graft of acellular allo-dermal matrix and
      auto-microskin on escharectomy after deep burns].
AB  - OBJECTIVE: To present the clinical application of composite graft of acellular
      allo-dermis matrix (ADM) with thin auto-microskin on burn wound. METHODS: 8
      inpatients with 18 full thickness skin burn wounds were transplanted with allo
      ADM after eschar was excised, then the auto-microskin and allo-human skin were
      covered on the area of the matrix, the wound where no allo-ADM grafting were
      covered as control groups only with auto-microskin and allo-human skin. The area
      of donor to wound is 1:5 - 1:8. RESULTS: Survived rate of 18 pieces composite
      skin that allo-ADM with auto-microskin were grafted were 94%. After following up
      for 3 to 13 months, the skins of complex grifting had well elastic and smooth
      texture compared to auto-microskin grafted, they appeared less cicatrisation and
      ulceration. 3 months after operation, it was indicated by histological
      examination that tightknit the epithelial-dermal conjunction and epidermal
      papilla structure could be identified in the allo-ADM skin and there were orderly
      collagenous fibres, but scar skin structure was observed in that auto-microskin
      grifted area. CONCLUSION: The graft effectiveness of allo-ADM and auto-microskin
      was better than that of auto-microskin, and this method could be used on major
      deep burn wound healing.

PMID- 15144666
TI  - [Relationship between epithelial-immunologic cells transdifferentiation and
      pseudoepitheliomatous granuloma lesion].
AB  - OBJECTIVE: Inappropriate treatment at early stage of wound could result in the
      formation of pseudoepitheliomatous granuloma (PEG). The correlation of abnormal
      transdifferentiation of epithelial cells to immunologic cells and the occurrence
      of PEG lesion was investigated. METHODS: Morphological change of epithelial
      tissue was observed with histopathology in 11 specimens of PEG lesions and 6
      specimens of normal skins from PEG edge (PEG-N) from 11 patients with damaged
      skin. The expression characteristics and distribution of pan-cytokeratin (CKp),
      IV type collagen, laminin (LM), epithelial cadherin (E-Cad), beta-catenin (beta
      Cat), focal adhesion kinase (FAK), stem cell factor (SCF) and its receptor-c-Kit,
      proliferating cell nuclear antigen(PCNA), and cluster of differentiation-14
      (CD14), CD68 and mast cell tryptase (MCT) in PEG were detected with the
      immunohistochemical and the indirect immunofluorescent double-staining. RESULTS:
      In comparison with PEG-N, epithelial tissue take on squamous metaplasia, and
      stroma was infiltrated with intensive microvessels and inflammatory cells in the
      PEG lesion. Poor epithelial basal layer constitution, basal polarization, and
      migration of basal cells to stroma could be observed. In the ultrastructure, the
      loose intercellular junction of basal cells and the increased nucleus/cytoplasm
      ratio and intercellular space could be observed, neonatal monocytoid cells and
      macrophages and mast cells as a exuviate-like manner brooded from cytoplasm of
      original epithelial cells and basement membrane. protein expression of CKp and E
      Cad by basal cells was significantly decreased, and the IV type collagen and LM
      protein could not be found in basement membrane of identical locus. By contrast,
      the immunoreactivity of beta-Cat and FAK was apparently increased. In addition,
      CD14(+) monocytes, CD68(+) macrophages, MCT(+) mast cells and CD68(+)/MCT(+)
      cells with various size, and these cells of stronger immuno-staining of SCF, c
      Kit and PCNA antigen could be found in epithelial tissue and stroma. CONCLUSION:
      Epithelial cells in PEG related to wound are characteristized by
      transdifferentiation of epithelial cells to immunologic cells, wich may be
      associated with local infectious and inflammatory reaction, ultimately resulting
      in enhancement the ratio of beta-Cat/E-Cad signal and activation SCF-c-Kit signal
      pathway. The phenomena of transdifferentiation epithelial cells in the PEG lesion
      will help to recognize of the neoplatic immune and trauma repair mechanism.

PMID- 15144669
TI  - [Liver transplantation for hepatocellular carcinoma: a report of 60 cases].
AB  - OBJECTIVE: To evaluate the role of orthotopic liver transplantation (OLT) in
      treatment of hepatocellular carcinoma (HCC) and the selection of recipients.
      METHODS: OLT was performed in 60 patients with HCC at Organ Transplantation
      Centre of the First Affiliated Hospital of Sun Yat-sen University between
      September 1993 and September 2002. Medical records were retrospectively analyzed
      with regard to the response to OLT and survival. RESULTS: One-month, 1, 2, 3-year
      survival rate of 23 liver transplant performed from September 1993 to July 2002
      were 73.9%, 60.9%, 43.5% and 29.0%, respectively. One-month, 1, 2-year survival
      rate of 37 liver transplant performed from August 2000 to September 2002 were
      89.2%, 75.8% and 61.2%, respectively. One-month survival rate was significantly
      greater in the patients with a preoperative liver function of Child A or B than
      Child C (P < 0.05). One-month, 1, 2, 3-year survival rate of small HCC (single
      tumor <or= 5 cm diameter or less than 3 tumors and tumors <or= 3 cm maximum
      diameter, n = 19) and large HCC (tumors > 5 cm diameter, n = 41) were 84.2%,
      76.6%, 65.6%, 65.6% and 82.9%, 63.1%, 46.7%, 37.4%, respectively. The median
      survival of large HCC was 18.0 months and mean survival of small HCC was 29.6
      months, respectively. The recurrence rate of small HCC and large HCC were 15.8%
      and 27.7%, respectively. There was no significant difference between the
      cumulative survival of small HCC and large HCC. The quality of life of patients
      with long-term survival was good. CONCLUSIONS: HCC associated with cirrhosis can
      be effectively treated by OLT on condition that no extrahepatic spread and no
      vascular involvement. OLT is recommended for treatment of small HCC combined with
      liver cirrhosis, meanwhile, OLT performed in the partial large HCC still is
      reasonable at the present time.

PMID- 15144670
TI  - [The classification and management of pancreatic duct stone].
AB  - OBJECTIVE: To set up a stand for surgical classification of pancreatic duct stone
      and evaluate the benefits of different management according to the
      classification. METHODS: Retrospectively analysis the diagnosis and prognosis of
      different management of 33 cases pancreatic duct stones to establish a new
      standard of classification and strategy of management of pancreatic duct stone.
      RESULTS: According to the results of imaging examination (B-US, CT, ERCP) and
      finding during surgery, pancreatic duct stone can be classified into four
      different types: Type I: The stones mainly located in the head of pancreas.
      Endoscopic pancreas drainage and remove of stones is the first line choice of
      treatment. If it fail the Whipple procedure should be applied. Type II, The
      stones mainly located in the body of pancreas. It can be treated by Pusetow
      procedure. Type III, The stones mainly located in the tail of pancreas. The
      resection of the tail of pancreas or combined with spleenectomy was recommended
      for the management of this type stones. Type IV, The stones can be found from the
      head to tail of the main duct of pancreas. The Pusetow-Gillesby procedure or
      dividing of the neck of pancreas removing stones from both ends of pancreatic
      duct and reconstructed by two ends pancreatic duct-ileostomy in Roux-en-Y fashion
      are the choice of management. CONCLUSION: The invadulaized strategy of the
      management based upon correct diagnosis and classification play the most
      important role in the treatment of pancreatic duct stone.

PMID- 15144671
TI  - [Paraaortic lymph node micrometastasis in advanced gastric cancer and its
      significance in prognosis].
AB  - OBJECTIVE: Paraaortic lymph nodes dissection in advanced gastric carcinoma is
      controversial. Investigation of micrometastasis in these critical lymph nodes is
      important in the evaluation of prophylactic lymphadenectomy. METHODS: A total of
      2 339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with
      advanced gastric carcinoma were examined immunohistochemically using cytokeratin
      antibody. RESULTS: Paraaortic lymph node metastasis was found in 95 of 390 nodes
      of 14 patients by routine histological examination. Micrometastasis in the
      paraaortic lymph nodes was immunohistochemically detected in 45 of 295 negative
      nodes from 15 of 33 patients. The 5-year-survival rate in patients with
      paraaortic lymph node metastasis was 56.0% in the node negative group, 25.2% in
      the cytokeratin positive group and 9.0% in the hematoxilin and eosin positive
      group. CONCLUSIONS: We have demonstrated a high rate of micrometastasis in the
      paraaortic lymph nodes of patients with advanced gastric carcinoma and have
      confirmed that prophylactic lymphadenectomy of these nodes is effective for such
      patients.

PMID- 15144672
TI  - [Overcoming multi-drug resistance using anti-MDR1 ribozymes].
AB  - OBJECTIVE: To reverse multidrug resistance (MDR) of HepG2 by anti-MDR1 hammerhead
      ribozyme. METHODS: We developed an anti-MDR1 hammerhead ribozyme and delivered it
      to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral
      vector containing RNA polymerase III promoter. We detected the expression of
      MDR1/Pgp and Rz in HepG2, HepG2 multidrug-resistant cell line and HepG2 Rz
      tranduced cells by real-time RT-PCR, semi-quantitative RT-PCR and western blot
      methods. Moreover, MTT assay was tested to detect sensitivity of these ribozyme
      tranduced cells, and Rhodamine123 (Rh123) applied to test the function of Pgp.
      RESULTS: The Rz-tranduced HepG2 cells became doxorubicin-sensitive, concomitant
      with the decreases in MDR1 expression, P-gp amounts and efflux pump function.
      CONCLUSIONS: The approaches using either retrovirus or liposome-mediated transfer
      of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR
      cells.

PMID- 15144673
TI  - [Experimental study on iNOS gene transfer mediated by liposome to treat portal
      hypertension in cirrhotic rats].
AB  - OBJECTIVE: To evaluate the effects of iNOS gene transfer on portal hypertensive
      rats. METHODS: Eukaryotic expression plasmid pcDNA(3)/iNOS was used to transfect
      sinusoidal endothelial cells (SEC) mediated by Lipofectamine. Transfection rate
      and gene exspression were detected. Hepatic cirrhosis was induced in male Sprague
      Dawley rats by intraperitoneal injection of carbon tetrachloride, and the
      cirrhotic rats were divided into three groups:Liposome-pcDNA(3)/iNOS (n = 10),
      Tris buffer (n = 10) and nude plasmid (n = 10), which were injected into the
      portal vein of experiment cirrhotic rats respectively. Five days later, animals
      were killed, immunohistochemistry and spectrophotometry methods were used to
      measure the expression of iNOS and the amount of NO production. RESULTS:
      Eukaryotic expression plasmid pcDNA(3)/iNOS could effectively transfect SEC and
      express corresponding gene products. Following iNOS gene transfer, compared with
      the two controlled groups, iNOS expression and the NO production were
      significantly increased meanwhile portal pressure was decreased significantly.
      CONCLUSIONS: The iNOS gene transfer is a feasible and an effective approach to
      treat portal hypertension in cirrhotic rats which could increase the expression
      of intra-hepatic iNOS and the amount of NO production thus leading to a
      remarkable reduction of portal venous pressure.

PMID- 15144674
TI  - [The expression of Cyclin D1 modulated by somatotropin on human pancreas cancer
      cell lines Bxpc-3].
AB  - OBJECTIVE: To observe the growth effect of somatostapin on human pancreas cancer
      lines Bxpc-3. METHODS: The Bxpc-3 pancreas cancer cells were treated with
      Somatotropin. The cells hyperplasia were detected by MTT and were observed
      apoptosis cells determinated quantitatively by TUNEL, quantify immune fluoresence
      double marked the proliferation cells and apoptosis cells, the expression of
      Cyclin D1 detected by immunohistochemical. RESULTS: The growth effect of pancrea
      cancer cells were limited by 10(-7) M, 10(-8) M, 10(-9) M Somatotropin on 2 day.
      The limited effect was decreased from 3 day. The cells proliferation were
      increased by somotostapin on 4day to 5day. The relationship between the
      expression of Cyclin D1 and apoptosis was negative correlation and the cells
      hyperplasia was positive correlation in Bxpc-3 cell line. CONCLUSION: From the
      cell study we knew the expression of Cyclin D1 reflected the prolefiration of
      pancreas cancer cells.

PMID- 15144675
TI  - [Experiment and study of endothelialization of prostheses with bone marrow CD34+
      cells].
AB  - OBJECTIVE: To exploration the endothelialization of prostheses with bone marrow
      CD(34)(+) cells. METHODS: CD(34)(+) cells were isolated from bone marrow of
      carine by an immune magnetic cell sorting system and induced into endothelial
      cells with VEGF. Seeding the cells to PTFE prostheses which implanted the
      abdominal aorta artery (AAA) and inferior vena cava (IVC). RESULTS: The isolated
      cells from bone marrow were CD(34)(+) by flow cytometer which could differentiate
      into endothelial cells in vascular endothelial growth factor (VEGF). The
      endothelial cells were identified by immunostaining and transmission electron
      microscope. The obliteration rate of the seeding grafts implanting AAA was 0%,
      the stenosis rate 12.5%; the obliteration rate implanting IVC 12.5%, the stenosis
      rate 25%. CONCLUSION: CD(34)(+) cells were isolated from bone marrow by an immune
      magnetic cell sorting system and were able to be induced into endothelial cells
      with VEGF in vitro. PTFE prostheses seeding CD(34)(+) cells have the ideal
      endothelialization and patency.

PMID- 15144682
TI  - [The application and early result of rectangle titanium cage in the anterior
      cervical spine fusion].
AB  - OBJECTIVE: To evaluate the value of rectangle titanium cage (SynCage-C) in the
      anterior cervical spine fusion. METHODS: Nineteen patients underwent anterior
      cervical discectomy and interbody fusion using SynCage-C with average follow-up
      of 9 months. RESULTS: All cases had cervical spondylosis with 13 cases of
      myelopathy and 6 cases of radiculopathy. One level fusion were 16 cases and two
      levels were 3 cases. The mean operation time was 40 minutes per level with
      average bleeding 60 ml. Patients were asked to wear a hard collar for average 8.5
      weeks after the operation. The fusion was solid on lateral view X-ray films three
      months post-operation. Only 1 case had neck stiffness due to prolonged collar
      protection and another case had short term pain on bone dorner site. There were
      no other complications such as cage subsidence, displacement, milaligment and
      kyphosis of cervical spine. CONCLUSION: The SynCage-C can resort and maintain the
      intervertebral space effectively with the advantage of immediate stability,
      satisfactory fusion and easy to use.

PMID- 15144683
TI  - [Design and preliminary clinical application of transoralpharyngeal atlantoaxial
      reduction plate].
AB  - OBJECTIVE: To design transoralpharyngeal atlantoaxial reduction plate (TARP),
      evaluate its biomechanical performance and observe its preliminary clinical
      effect. METHODS: A brand-new TARP system was designed, including butterfly
      titanium alloy plate, self-locking screws, atlantoaxial reductor and other
      operation instruments. Twelve fresh occipital bone-C(3) specimen were designed
      for biomechanical test including range of motion (ROM) (n = 6) and screw pull-out
      strength (n = 12). Preliminary clinical application of TARP was reported.
      RESULTS: The reduction mechanism of the TARP system was designed cleverly. TARP
      had equal effect with Magerl + Brooks and it was more stable than the other three
      clinically widely used atlantoaxial fixators: Magerl, Brooks and anterior
      transarticular screw fixation through C(2) vertebral body. TARP's C(1) and C(2)
      screws were strong enough for atlantoaxial arthrodesis and their antipull-out
      performance was excellent. Clinical application on irreducible atlantoaxial
      dislocation proved that TARP had the function of instant reduction, the operation
      was feasible and the operation effect was significant. CONCLUSION: TARP's design
      is novel and it has excellent biomechanical performance. The operation procedure
      is simple and reasonable. Furthermore, instant reduction could be completed
      during the operation and the fixation is strong. Above all, TARP is creative and
      will have excellent prospect.

PMID- 15144684
TI  - [Long-term follow-up on disc renarrowing after anterior lumbar interbody fusion
      with autogenous tricortical iliac crest graft].
AB  - OBJECTIVE: To have a retrospective review of the patients undergoing anterior
      lumbar interbody fusion (ALIF) with clinical and radiological assessment, and
      observe changing of graft after procedure and assess correlation between graft
      collapse and recurrence of radiculopathy. METHODS: Sixty-seven consecutive
      patients undergoing ALIF only at L(4 - 5) with autologous iliac crest graft for
      intervertebral disc prolapse were followed-up for an average of 14 (2.5 - 32)
      years. The effect of the fusion was examined by the existence of radiolucent
      lines and bony continuity on plain radiographs and tomographs, or mobility on
      flexion-extension radiographs. The disc height was also measured. Lower limb
      radiculopathy was assessed based on the symptom and examination. Paired samples t
      test was used for statistical analysis. RESULTS: Sixty-four patients with
      successful fusion were analyzed (fusion rate: 96%). All measurements in this
      study were completed by the same author, and the measurement error of more than 2
      mm was statistically significant. According to this, graft collapse occurred in
      55 patients (86%) and 9 patients (14%) had no graft collapse. In these 55 cases,
      the original disc height was (12.1 +/- 2.9) mm, increased immediately after the
      surgery to (16.2 +/- 1.9) mm, however re-narrowed to (12.9 +/- 2.7) mm at the
      first observation of solid fusion (a mean of 9 months, ranging from 5 to 14
      months), which was not significant different compared to the original. There was
      no significant change in disc height after solid fusion and the disc space at the
      final follow-up was (12.6 +/- 2.3) mm. There was no radiculopathy observed in 52
      cases (95%) during the follow-up. CONCLUSION: Disc space re-narrowing was
      observed in most cases after single level ALIF of L(4 - 5), however it was rarely
      less than the initial and unlikely to result in recurrence of radiculopathy.

PMID- 15144685
TI  - [Treatment of spinal fractures complicating ankylosing spondylitis].
AB  - OBJECTIVE: To study the treatment of spinal fractures in ankylosing spondylitis.
      METHODS: Nineteen cases of spinal fractures complicating ankylosing spondylitis
      admitted in our hospital were studied retrospectively. RESULTS: All of 19 cases
      were up to the diagnosis standards of ankylosing spondylitis. Eleven patients had
      cervical fracture and 8 had thoracolumbar fracture. Of the patients with cervical
      fracture, fractures occurred at C(5 - 7) in 9 patients. Of the patients with
      thoracolumbar injury, stress fractures were seen in 7 patients and all of seven
      fractures occurred at T(10)-L(2). Sixteen of the 19 patients sustained fractures
      through three columns of the spine. Nine patients had spinal cord injures; eight
      of the 9 cases had cervical fracture. All of the 19 patients were treated
      operatively. Four different surgical procedures were used in patients with
      cervical fracture; decompression, fusion and stabilization with instrumentation
      by anterior approach were performed in 9 patients. Of the patients with
      thoracolumbar fractures, four different operations were performed; fusion by both
      anterior and posterior approach plus a long posterior instrument were used in 5
      cases. Eighteen patients had an average follow-up period of 46.6 months. Nine
      patients with preoperative neurological deficits improved in 8 and was stabilized
      in 1. Radiographic evidence of fusion was observed in all of the 18 patients. Two
      patients suffered neurological deterioration during surgery. One patient died
      from cerebrovascular infarction. Two patients had pneumonia after the operative
      procedure. CONCLUSIONS: Spinal fractures in ankylosing spondylitis are associated
      with a high rate of neurological injury. Shearing fracture usually occurs at the
      lower cervical spine (C(5 - 7)) and stress fracture at thoracolumbar spine. Most
      of the fractures involve three columns of spine. Surgical intervention may be
      indicated in this injury. Fracture union and neurological improvement can be
      achieved in most patients treated by operation. We suggest that, fusion and
      stabilization with instrumentation by anterior approach is indicated in most
      cervical shearing fracture, and a combined fusion by both sides plus a long
      posterior instrument is probably beneficial in patients with thoracolumbar stress
      fracture. Complications is not rare after surgery and appropriate preventive
      measures are necessary for these patients.

PMID- 15144686
TI  - [Minimally-invasive surgical treatment of cervical radiculomyelopathy].
AB  - OBJECTIVE: To discuss the effect of the posterior minimally-invasive surgical
      treatment of root type cervical spondylotic myelopathy. METHODS: A posterior
      minimally-invasive operation was given to 32 nerve root type cervical spondylotic
      myelopathy patients, and the clinical result was followed. RESULTS: An operation
      of enlargement of intervertebral foramen and disc excision was given for 14 young
      patients whose ligamentum flavum incrassated a little and the disc was soft. An
      operation of enlargement of intervertebral foramen only was given for 18 old
      patients whose ligamentum flavum incrassated much with ossification, and the disc
      was tenacious. All the patients' sign of nerve root was improved after operation.
      Twenty-eight patients were followed up 3 to 16 months, and there were no obstacle
      of neck movement and recurrence of clinical sign. CONCLUSION: This method for the
      posterior minimally-invasive neurosurgical operations of cervical spondylotic
      myelopathy is safe, simple and effective. By this operation, we can removal most
      of the herniative cervical disk and decompression for the nerve root and get good
      stable of spondylopathy.

PMID- 15144687
TI  - [Biomechanical study of percutaneous pinning as the treatment of proximal humerus
      fractures].
AB  - OBJECTIVE: To investigate the influence on fracture stability by different pin
      construct during percutaneous pinning for the treatment of proximal humerus
      fractures. METHODS: Eighteen pairs (36) adult fresh-frozen humeri were match
      paired and divided into 4 groups. Dual-energy bone density scan had been used in
      order to rule out the influence by different degrees of osteoporosis of the
      cadaver. Two-part surgical neck fracture model was carried out unanimously in all
      36 humeri. Four terminal threaded pins (2.5 mm in diameter) were used in fixation
      for all specimen. Parallel type pinning (box type) were carried out in 2 groups
      and convergent type pinning (fan shape) in the other 2 groups. Instron5566
      biomechanical tester was applied in determining both anti-shear and anti-torsion
      ultimate load of each specimen. RESULTS: There was no statistical difference
      between parallel pin construct and convergent construct in regard of anti-shear
      resistance (P = 0.73). But by mean of anti-torsion resistance, the parallel
      construct had significant advantage over the convergent construct (P = 0.04).
      CONCLUSION: According to our biomechanical data, parallel pin construct seems to
      have better torsional stability. We suggest that parallel pin fixation should be
      applied whenever possible. Convergent pin construct should be considered when
      parallel construct is not possible or the distance between pins are too small (<
      1 cm).

PMID- 15144688
TI  - [Clinic effect of alendronate sodium treatment in osteoporosis patients with hip
      fracture].
AB  - OBJECTIVE: To assess efficacy and safety of alendronate sodium treatment in
      osteoporosis patients with hip fracture. METHODS: One year randomized, double
      blind clinical trial was carried out in 77 osteoporosis patients with hip
      fracture. The bone mineral density (BMD) in lumbar spine (L(2 - 4)), femoral neck
      (Neck), Wards triangle (Wards) and great trochanter (Troch) was measured by dual
      energy x-ray absorptiometer (DEXA). RESULTS: In our study, alendronate sodium
      induced marked increases in BMD of the L(2 - 4) (7.0% +/- 13.0%), Neck (7.3% +/-
      11.1%), Wards (4.6% +/- 5.9%), Troch (4.5% +/- 3.2%) (mean +/- s) versus
      decreases of 2.0% +/- 4.5%, -0.9% +/- 6.9%, 3.6% +/- 4.9% and 1.14% +/- 6.0% with
      placebo (P < 0.05). Blood Ca, P, ALP, BGP and Urine Pyd/C were no significant
      difference between before and after therapy. There were usually mild and
      transient side-effect, such as gastrointestinal symptoms. CONCLUSION: Alendronate
      is an efficacy and safety drug in treatment of osteoporosis.

PMID- 15144690
TI  - [The change of renin, endothelin and prostaglandin in blood during long time left
      ventricular assist].
AB  - OBJECTIVE: To monitor the change of renin, endothelin and 6-keto-prostaglandin
      F1alpha in canine during left ventricular assist (LVA). METHODS: Eight canines
      were assisted by left assist ventricular device for 9 hours. The level of renin,
      endothelin and 6-keto-prostaglandin f1alpha in plasma were measured by
      radioimmunity analysis before assisting (control group) and at 3 hours, at 6
      hours, at 9 hours after assisting. RESULTS: The level of endothelin in plasma
      didn't dropped remarkably as LVA proceeded in which there was not differency in
      statistical diffency compared with control group[(51 +/- 11) ng/L, (42 +/- 8)
      ng/L, t = 0.926, P > 0.05]; The level of renin in plasma reached the summit at 3
      hours during LVA compared with control group (3,036 +/- 1,411) ng/L, (1,783 +/-
      467) ng/L, t = 5.013, P < 0.01) and later show dropping tendency without
      statistical differency at 9 hours (1 944 +/- 883) ng/L (t = 0.644, P > 0.05); The
      level of 6-keto-prostaglandin f1alpha in plasma at 3 hours during assisting
      increased remarkably [(75 +/- 17) ng/L, t = 1.411, P < 0.05), at 6 hours reached
      summit [(92 +/- 18)ng/L, t = 3.533, P < 0.01) and at 9 hours show dropping
      tendency with significant differency compared with control group (90 +/- 22)
      ng/L, t = 2.516, P < 0.05). CONCLUSION: During 9 hours LVA, endothelin didn't
      dropped remarkably compared with control group and the endothelium released renin
      with transient increase, prostaglandin with consistent increase.

PMID- 15144689
TI  - [The therapeutic effect of nanometer silver impregnated dressing on gunshot
      wounds after being immersed in brine and tapwater in rabbits].
AB  - OBJECTIVE: To investigate the therapeutic effect of nanometer silver impregnated
      dressing on gunshot wounds after being immersed in brine and tapwater in rabbits.
      METHODS: Rabbits were randomly divided into two groups after receiving gunshot
      wounds in both lower limbs. In group 1, the wounded limbs on the experimental
      side were immersed in brine for 5 h; in group 2, the wounded limbs on
      experimental side were immersed in tapwater for 5 h. All the wounds were treated
      with nanometer silver impregnated dressing on the experimental sides, while those
      of the control sides were treated with vaseline dressing. Biopsy was done after
      30 min and 1, 2, 3, 4, 5 h, respectively. RESULTS: In group 1, the onset of
      inflammation around the wounds of the experimental sides was delayed, the
      inflammatory response was less serious, and the wounds were dry with less
      exudation compared to the controls. The mean healing time of the entry wounds on
      experimental and control sides was (29.4 +/- 6.6) d and (36.3 +/- 6.0) d (P <
      0.01), respectively, and that of the exit wounds on experimental and control
      sides was (20.1 +/- 6.0) d and (27.3 +/- 5.7) d (P < 0.01), respectively. In
      group 2, only one of the experimental wounds showed mild inflammation, while all
      of the control wounds showed serious inflammation with much exudation. The mean
      healing time of the entry wounds on experimentsides was (13.0 +/- 1.52) d, while
      that on control sides was (16.0 +/- 3.10) d (P < 0.01). The mean healing time of
      exit wounds on experimental sides was (11.0 +/- 2.75) d, and those of the control
      sides was (15.6 +/- 2.85) d (P < 0.01). CONCLUSION: The nanometer silver
      impregnated dressing can control infection and accelerate healing in gunshot
      wounds in rabbits.

PMID- 15144691
TI  - [p16 protein expression in the transplacental induced brain tumor in rat].
AB  - OBJECTIVE: To study in series the p16 protein expression on the rat brain tumor
      induced transplacentally by ENU. METHODS: The p16 protein expression was
      determined with immuno-histochemistry stain on the offspring's brain at their 60,
      90, 120, 150 days after birth. RESULTS: (1) p16 proteins were expressed in all of
      the brain samples in the 60-day group; occasionally negative in the 90-day group;
      partly expressed in the 120-day group; significantly less expressed in the 150
      day group. (2) The rate of expression in the tissue around tumor was higher than
      that in the tumor. (3) The p16 protein was mainly orientated in the nuclear of
      cell and sporadically orientated in the cytoplasm. CONCLUSION: (1) It shows the
      p16 protein expression decreases with the increase of tumor incidence in the rat
      brain, which accompanies the start and development of the induced tumor. So we
      speculate that the dysfunction of p16 gene is one of the factors related to tumor
      incidence in this animal model. (2) The p16 protein is mainly orientated in the
      nuclear of cell and sporadically orientated in the cytoplasm.

PMID- 15144693
TI  - [Potential mechanism underlying down-regulation of albumin expression induced by
      lipopolysaccharide in rat hepatocytes].
AB  - OBJECTIVE: To investigate the potential molecular mechanism underlying down
      regulation of albumin expression induced by lipopolysaccharide (LPS) in rat
      hepatocytes. METHODS: The albumin mRNA expression and albumin protein levels in
      the supernatant were observed at 0, 2, 8, 12 and 24 hours after 1 micro g/ml LPS
      treatment. The albumin mRNA expression was determined by RT-PCR, and albumin
      protein levels were assayed with EIA in the supernatant of hepatocytes pretreated
      with specific inhibitors of extracellular signal-regulated kinase (PD98059) and
      p38 kinase (SB203580). RESULTS: The albumin mRNA expression was reduced to 70% of
      baseline value, meanwhile, the albumin protein concentration in the supernatant
      was reduced by 50% compared with the controls after 24 hours of LPS treatment.
      Pretreatment with PD98059 and SB203580 did significantly inhibit the reduction of
      albumin by LPS at the given dose. CONCLUSION: The results indicate that LPS can
      induce the reduction of albumin synthesis by down-regulation of albumin mRNA
      expression at transcription level, and the process may be related to the signal
      transducation of extracellular signal-regulated kinase and p38 kinase.

PMID- 15144705
TI  - [Pediatric medical education needs to be reformed].

PMID- 15144694
TI  - [Effects of substance P on granulation tissue fibroblasts proliferation and
      expression of basic fibroblast growth factor mRNA].
AB  - OBJECTIVE: To explore the proliferation-promoting effect of sensory neuropeptide
      substance P (SP) on the cultured granulation tissue fibroblasts in vitro and its
      regulative effect on the gene expression of basic fibroblast growth factor (bFGF)
      mRNA. METHODS: The proliferation-promoting effect of cultured granulation tissue
      fibroblasts was observed by means of MTT; the regulative effect of SP on gene
      expression of fibroblast bFGF by RT-PCR. The time and dose-efficiency relations
      were also observed. RESULTS: There was a significant proliferation-promoting
      effect of SP on the cultured granulation tissue fibroblasts in vitro in a
      remarkable dose-dependent fashion. However, bFGF antibody only partly exerted its
      inhibitive effect. SP could induce the bFGF mRNA expression of the fibroblasts at
      the 3rd and 6th hour (P < 0.01). SP could promote the bFGF mRNA expression of the
      fibroblasts in the concentration of 10(-9) - 10(-5) mol/L and peaked in the
      concentration of 10(-7) mol/L. CONCLUSIONS: SP has a significant proliferation
      promoting effect on the granulation tissue fibroblasts, which is correlated with
      SP inducing bFGF mRNA expression of fibroblasts.

PMID- 15144706
TI  - [A case report of facial malignant granuloma].

PMID- 15144707
TI  - [Long-term outcome and cardiac arrhythmias in infants with right atrial
      isomerism].
AB  - OBJECTIVE: The investigators compared the outcome of infants and children having
      right atrial isomerism with normal pulmonary venous drainage to those with
      anomalous drainage and determined factors associated with poor outcome. They
      further determined the prevalence of symptomatic cardiac arrhythmia in these
      patients and its relation to long-term morbidity and mortality. METHODS: The
      authors made a retrospective review of management and outcome of 116 infants and
      children diagnosed to have right atrial isomerism between January 1980 and
      December 2000. The type, timing and precipitating factors of symptomatic cardiac
      arrhythmia that occurred in patients, among a cohort of 85 who had or are
      awaiting surgical interventions, were noted. RESULTS: The 116 patients presented
      at a median of 1 day (range 1 day to 3.7 years) with cyanosis in the majority
      (96%). No interventions were planned in 31 (27%) patients who all died. The early
      surgical mortality for pulmonary venous repair was 25% (2/8), Fontan procedure
      26% (5/19), cavopulmonary shunting 8% (1/13) and systemic-pulmonary arterial
      shunt insertion 2% (1/53). Late mortality was related to infection (n = 10),
      sudden death of unknown aetiology (n = 7) and documented arrhythmia (n = 1).
      Patients with obstructed anomalous pulmonary venous drainage had poor survival (P
      < 0.001). The mean (SEM) survival estimates for those with normal pulmonary
      venous drainage at 1, 5, 10 and 15 years were 81 (5)%, 67 (7)%, 60 (8)% and 43
      (12)%, respectively, similar to those of patients with non-obstructed anomalous
      drainage (P = 0.06). Independent risk factors for mortality included pulmonary
      venous obstruction (relative risk RR 3.8, P = 0.001) and a single ventricle (RR
      2.9, P = 0.016). Symptomatic cardiac arrhythmia occurred in 15/85 (18%) patients;
      11 of whom had supraventricular tachycardia, and 1 atrial tachycardia, 1 atrial
      flutter, 1 ventricular tachycardia and 1 congenital complete heart block. The
      arrhythmias occurred before surgery in 4, early after surgery in 5, and late
      after surgery in 6 patients. Freedom from arrhythmia at 1, 5, 10, 15 and 20 years
      was (93 +/- 3)%, (86 +/- 4)%, (80 +/- 6)%, (73 +/- 9)% and (48 +/- 15)%,
      respectively. Logistic regression failed to identify any risk factors for
      symptomatic arrhythmia. CONCLUSION: The long-term outcome of infants and children
      with right atrial isomerism, whether associated with normal or anomalous
      pulmonary venous drainage, remains unfavourable. Sepsis and sudden death are
      major causes of late mortality. While symptomatic cardiac arrhythmias are not
      uncommon. They do not seem to relate to the overall high mortality and occurrence
      of sudden death in this patient group. Nonetheless, detailed assessment and
      aggressive management of cardiac arrhythmias once they occur are warranted in
      light of the precarious single ventricular haemodynamics.

PMID- 15144708
TI  - [Changes of endogenous hydrogen sulfide (H2S) in hypertensive rats].
AB  - OBJECTIVE: Hydrogen sulfide, a well known toxic gas, has been found to play
      important roles in many organs and tissues, especially in cardiovascular system
      recently. The aim of this study was to explore the producing rate of hydrogen
      sulfide (H(2)S) in aorta and the level of H(2)S in plasma of spontaneous
      hypertensive rats (SHR), and to study the role of H(2)S on the development of
      hypertension. METHODS: Twenty-four male SHR rats at the age of 4 weeks were
      randomly divided into SHR control group, SHR + NaHS (H(2)S donor) group and SHR +
      DL-propargylglycine (PPG) group, respectively. Another twenty-four male WKY rats
      were also divided into WKY control group, WKY + NaHS group and WKY + PPG group.
      SHR control and WKY control rats were injected with water. Rats of SHR + NaHS
      group and WKY + NaHS group were injected with NaHS, and rats of SHR + PPG group
      and WKY + PPG group were injected with PPG every day. Five weeks later, the blood
      pressure and the left-to-whole heart weight ratio were determined. The producing
      rate of H(2)S in aorta and the H(2)S level in plasma were also detected. RESULTS:
      The producing rate of H(2)S in aorta and the plasma level of H(2)S in SHR groups
      were all less than those of the corresponding WKY groups, however, the
      differences between SHR + PPG group and WKY + PPG group were not significant (P >
      0.05). The producing rate of H(2)S and the plasma level of H(2)S in SHR + PPG
      group were similar to those of SHR control group. The producing rate of H(2)S and
      the plasma level of H(2)S in SHR + NaHS group were higher than those of SHR
      control. Both the producing rate and the plasma level of H(2)S in WKY + PPG group
      were less than those of WKY control. The producing rate of H(2)S in aorta of WKY
      + NaHS group was higher than that of WKY controls, while the plasma level of
      H(2)S in WKY + NaHS group was not different from that of WKY controls
      significantly. The blood pressure of SHR groups increased compared with that of
      WKY groups (P < 0.05). The blood pressure of SHR + PPG group was similar to that
      of SHR controls, while the blood pressure of SHR + NaHS reduced significantly
      compared with that of SHR controls. The blood pressure of WKY + PPG group was
      higher than that of WKY controls while the blood pressure of WKY + NaHS was
      similar to that of WKY controsl. CONCLUSIONS: H(2)S plays an important role in
      maintaining normal pressure and the reduced production of endogenous H(2)S is an
      essential factor in the development of spontaneous hypertension. Exogenous H(2)S
      provides a new way for interfering with the progression of hypertension.

PMID- 15144709
TI  - [Correlation between mannose-binding lectin gene codon 54 polymorphism and
      susceptibility of Kawasaki disease].
AB  - OBJECTIVE: Human mannose-binding lectin (MBL) is a C-type serum lectin
      synthesized by the liver as an acute-phase protein. MBL can bind to glycoproteins
      terminated with mannose and N-acetylglucosamine present in the cell walls on a
      variety of microorganisms. Therefore, MBL appears to play an important role in
      the immune system. Low levels of MBL in human have been associated with a
      susceptibility to recurrent infections. MBL deficiency and low serum MBL levels
      are strongly associated with the presence of three point mutations at codon 52,
      54 and 57 of exon 1 in the human MBL gene, and in Chinese population, the codon
      54 mutation occurs at a frequency of 0.11 - 0.17. The data suggested that MBL
      insufficiency might also predispose to the development of autoimmune diseases
      such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The
      possibility that Kawasaki disease (KD) is an infectious disease has been
      discussed and investigated for decades, in light of the implication that
      infections are involved in the pathogenesis of KD. It has been suggested that MBL
      insufficiency might predispose to the occurrence of KD. This study was aimed to
      investigate the genetic association of MBL codon-54 polymorphism in patients with
      KD, and to investigate possible associations with clinical manifestations of the
      disease. METHODS: There were 95 patients with KD and 160 healthy subjects in the
      study. The genotype of MBL gene 54 codon was detected by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical
      characteristics and biochemical examination were also performed. RESULTS: The
      genotype frequency of heterozygote (GGC/GAC) was significantly higher in KD group
      than that in healthy subjects (45.2% vs 25.0%, P < 0.01), and the allele
      frequency of GAC mutation was also higher in KD patients than that in control
      group (0.258 vs 0.138, P < 0.01). The variant allele (GAC) was markedly
      associated with KD (OR = 2.18, 95% CI = 1.38 approximately 3.44, P < 0.05). But
      there was no significant difference in the allele frequency of GAC between
      patients with and without coronary artery lesion (CAL) in KD cases (0.281 vs
      0.246, P > 0.05). In addition, in cases of KD, more patients carrying the variant
      allele (GAC) had episodes of upper respiratory or gastrointestinal infections
      prior to the onset of KD than wild homozygotes (P < 0.01). CONCLUSION: The codon
      54 polymorphism of MBL gene was associated with KD. It is possible that MBL gene
      codon 54 mutation might be related to the pathogenesis of KD.

PMID- 15144710
TI  - [Neuronal differentiation and TrkA expression of neuroblastoma induced by the
      combination treatment of interferon-gamma and NGF].
AB  - OBJECTIVE: Neuroblastoma (NB) is one of the most common solid tumors of early
      childhood. A small percentage of NB has been found to undergo spontaneous or
      chemotherapeutically induced regression or differentiation into benign
      ganglioneuromas. The differentiation therapy is a respective method in the
      clinical treatment of NB. OBJECTIVE: Interferon-gamma (IFN-gamma), nerve growth
      factor (NGF), and combination of IFN-gamma and NGF were used as induction drugs
      respectively to induce the differentiation of human SMS-KCNR cells. The cells
      were observed for morphological differences, growth arrest, and the TrkA mRNA
      expression of the 10th day-cells. METHODS: The human SMS-KCNR cell lines were
      cultured. The TrkA mRNA expression was detected by RT-PCR. Cell counts were
      measured by using a hemocytometer and the viability was assessed with the trypan
      blue exclusion. The morphological differentiation was observed under the phase
      contrast microscope. RESULTS: The simultaneous loading of NGF with IFN-gamma
      caused more prominent neurite outgrowth than independent treatment with either
      IFN-gamma or NGF in SMS-KCNR cells (P < 0.01). The cell proliferation was
      inhibited significantly in the former (P < 0.01). The TrkA mRNA level increased
      in the IFN-gamma group (P < 0.01). While there was no significant change of TrkA
      mRNA level in the NGF group (P > 0.05). The TrkA mRNA level was obvious decreased
      in the combination group (P < 0.01). CONCLUSION: In human SMS-KCNR cells, the
      combination of IFN-gamma and NGF showed prominent effect on the cell
      differentiation. In contrast with the induction of TrkA mRNA expression by IFN
      gamma, the combination treatment could decrease TrkA mRNA expression, which might
      indicate that a kind of negative feedback mechanism existed. These data suggest
      that using IFN-gamma and NGF together may be an appropriate strategy in the
      treatment of children with advanced neuroblastoma.

PMID- 15144711
TI  - [Effects of meisoindigo on the expression of globin gene in vitro].
AB  - OBJECTIVE: The pathophysiology of beta-thalassemia is the imbalance of the alpha
      and non-alpha globin chain which leads to a series of clinical symptoms of
      hemolytic anemia. Scientists continuously try to explore gene-activated drugs to
      increase the level of non-alpha globin chain or decrease the level of alpha
      globin chain in the treatment of beta-thalassemia. To probe into the effects on
      globin-gene expression of meisoindigo (Me) in cultured erythroid cells derived
      from peripheral blood, so as to provide the theoretical basis for applying Me in
      the treatment of beta-thalassemia. METHODS: By using the two-step liquid culture
      of erythroid progenitor cells and reverse transcription polymerase chain reaction
      (RT-PCR), and by using alpha mRNA as an inner control, the level of gamma mRNA
      and beta mRNA in cultured erythroid cells derived from peripheral blood of 11
      patients with severe beta-thalassemia and 6 normal volunteers were measured under
      the effect of different concentration (2.5 micro mol/L, 5 micro mol/L and 10
      micro mol/L) of Me. RESULTS: (1) No statistic significance was found in the ratio
      of beta/alpha mRNA by Me in cultured cells from both normal individuals and beta
      thalassemia. (2) Me can significantly increase the ratio of gamma/alpha mRNA and
      (beta + gamma)/alpha mRNA (that is non-alpha/alpha mRNA) in cultured cells from
      normal individuals and beta-thalassemia. The ratio of gamma/alpha mRNA was
      increased 0.31 - 0.45 times and the ratio of non-alpha mRNA/alpha mRNA increased
      0.21 - 0.32 times in Me induced cells from normal individuals. No significant
      result was observed among the different concentrations of Me (2.5 micro mol/L, 5
      micro mol/L and 10 micro mol/L) in normal individuals. With the increasing of Me
      concentrations, the ratios of gamma/alpha mRNA and alpha/alpha mRNA were
      increased in cultured cells from beta-thalassemia. The ratio of gamma/alpha mRNA
      was increased 0.33 - 1.17 times and the ratio of non-alpha/alpha mRNA increased
      0.25 - 0.89 times in Me induced cells from beta-thalassemia. There was no
      significant difference between the concentrations of 2.5 micro mol/L and 5 micro
      mol/L concentration in beta-thalassemia. However, there was significant
      difference between the concentrations of 10 micro mol/L and the concentrations of
      2.5 micro mol/L and 5 micro mol/L in beta-thalassemia. (3) The increase of the
      ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in beta-thalassemia was higher
      than that in normal individual with induction by Me with a higher concentration
      (10 micro mol/L). CONCLUSION: Me can raise the ratio of gamma/alpha mRNA and non
      alpha/alpha mRNA in cultured erythroid cells derived from peripheral blood of
      both normal individual and beta-thalassemia in the level of transcription, which
      can improve the imbalance of the alpha and non-alpha globin chain. So Me has a
      latent value in the therapy of beta-thalassemia.

PMID- 15144712
TI  - [The expression of CD19 in 210 cases of childhood acute leukemia and its
      significance].
AB  - OBJECTIVE: To investigate the expression of CD19 on childhood acute leukemia (AL)
      and its significance, and to provide evidence for the diagnosis and differential
      diagnosis as well as monoclonal antibody-targeting treatment of leukemia.
      METHODS: There were 210 cases of childhood AL, of which 130 cases were male and
      80 were female with a mean age of 9 years old. Using a panel of 27 fluorochrome
      directly labeled monoclonal antibodies, 210 samples from the patients were
      analyzed with CD45/SSC double parameters and multi-color flow cytometry to
      determine the expression of CD19. RESULTS: In the 93 cases of B lineage acute
      lymphoblastic leukemia (ALL), the positive rate (98.9%, 92/93) of CD19 was
      significantly higher than that of the other B cell related antigens, such as CD10
      (88.2%, 82/93, P = 0.003), CD20 (24.7%, 23/93, P = 0.001) and CD22 (60.2%, 56/93,
      P = 0.001). CD19 was expressed on all 8 cases of B/myeloid (My) hybrid acute
      leukemia (HAL) and 1 case of B/T HAL, but was not expressed on all 24 cases of T
      lineage leukemia and 5 cases of T/My HAL. In the 79 cases of acute myeloid
      leukemia (AML), only 5 (6.3%) cases expressed CD19. The positive rate (6.3%) of
      CD19 on AML was significantly lower than that on B lineage ALL (98.9%, P =
      0.001). The percentage of CD19 positive cells in B/My HAL (41.6% - 88.7% with a
      mean of 73.8%) was significant higher than that in CD19(+)-AML (21.4% - 50.4%
      with a mean of 24.2%; Run Sum test, P = 0.0084). Of the 210 cases, 102 were B
      lineage related AL including B lineage ALL, B/My HAL and B/T HAL. In B lineage
      related AL, the sensitivity and the specificity of CD19 was 99.0% (101/102) and
      95.4% (13/108) while the positive predictive and the negative predictive values
      to B lineage were 95.3% (101/106) and 99.0% (103/104), respectively. Using
      CD19(+) as a single reagent to diagnose B lineage, the false positive rate was
      4.6% (5/108) and the false negative rate was 1.0% (1/102) with a general
      diagnosis index (GDI) of 94.4% [GDI = 1-(false positive rate + false negative
      rate)]. CONCLUSION: CD19 is continuously and stably expressed on all stages of B
      lineage differentiation. It is a reliable cell membrane marker for diagnosing B
      lineage ALL and an ideal target for antibody-targeting treatment of leukemia as
      well; the expression degree of CD19 can be used to distinguish B/My HAL from
      CD19(+)-AML; CD19 didn't express on normal myeloid cells but did on some AML
      cells. Therefore it can be used to detect the minimal residual disease.

PMID- 15144714
TI  - [Application of metal hemoclip for endoscopic polypectomy in children with thick
      pedunculated intestinal polyps].
AB  - OBJECTIVE: With the development of endoscopic therapy in children, endoscopic
      electrocoagulation polypectomy had gradually replaced surgery and became an
      important method to resect gastrointestinal polyps in children. Simple
      electrocoagulation polypectomy could often bring some complications of
      gastrointestinal bleeding and perforation because of incomplete
      electrocoagulation or mechanical incision, especially in gastrointestinal thick
      pedunculated polyps which always have thick nutrient blood vessel. Hemoclips can
      successfully interdict arteriovenous blood because it can clamp tissue firmly
      without causing necrosis around the target area. Based on its good mechanical
      hemostasis, hemoclips are not only widely used in treating bleeding like from
      ulcer, tumor and variceal ligation but also used in removal of thick-pedunculated
      gastrointestinal polyps in adults. This paper describes the application of
      endoscopic electrocoagulation with metal hemoclips to remove thick-pedunculated
      intestinal polpys in children for the first time, sums up the experience and
      evaluates its efficacy and safety. METHODS: Between October, 2001 and December,
      2002, 5 cases with thick-pedunculated intestinal polpys were presented. The age
      of the patients ranged from 3 to 5 years. The clinical features were
      gastrointestinal bleeding or abdominal pain. The longest course of disease was 2
      years. Enough preparations for alimentary tract were necessary for polypectomy.
      The procedures were performed under general anesthesia in order to avoid the risk
      of bleeding aspiration. Endoscopy was performed in the standard fashion. The
      apparatus included electronic colonic endoscope (XQ 200, Fuji Corp, Tokyo,
      Japan), snare (XQ200, Fuji Corp, Tokyo, Japan), impeller of the clip (HX-5QR-1)
      and hemoclip (MD850) which could be passed through the biopsy channel of
      endoscope. The clip was completely covered with a hood avoiding any injury to the
      mucous membrane. The pedicel with diameter of more than 1.0 cm underwent
      endoscopic electrocoagulation polypectomy with hemoclips. The clip contacted
      polyps in upright direction. One or more hemoclips were selected to clamp the
      proximal basement of the pedicel in terms of the pedicel diameter. Turning of the
      red colour of polyps to purple suggested that hemoclip interdicted arteriovenous
      blood effectively. The clip was then shut off and electrocoagulation polypectomy
      was followed. Six polyps were observed and removed. RESULTS: Six polyps including
      2 transverse colon polyps and 4 descending colon polyps were resected.
      Pathological results showed that 3 were juvenile polyps and the other 3
      adenomatous polyps. All the polyps were completely resected. The diameter of
      pedicel were 1.2 - 2.2 cm. The head and pedicel of the biggest polyp was about 5
      cm x 5 cm and 2.2 cm, respectively, and five clips were used in order to remove
      it. No complications of bleeding and perforation were observed in these children.
      All hemoclips were expelled from intestines within one week. The symptoms of
      these patients disappeared. CONCLUSION: Mechanical hemostasis with hemoclips
      successfully interdicted arteriovenous blood of thick-pedunculated polyps.
      Hemoclips can successfully prevent the complications of bleeding and perforation.
      The clipping brings about a new method in endoscopic therapy. Endoscopic
      electrocoagulation polypectomy with hemoclips is a simple, safe and effective
      method to treat thick-pedunculated gastrointestinal polyps in children and it is
      a valuable tool in polypectomy for children.

PMID- 15144713
TI  - [A study on micromegakaryocyte in children with idiopathic thrombocytopenic
      purpura].
AB  - OBJECTIVE: Bone marrow megakaryocytes overly proliferate and abnormally develop
      among patients with idiopathic thrombocytopenic purpura (ITP). Previous studies
      showed that it resulted from the abnormal immune function of the body. But the
      changes in megakaryocytes, especially in micromegakaryocytes in this disease are
      unclear. The present study was designed to explore the growth and development
      status of megakaryocytes and the significance of changes in micromegakaryocytes
      in pediatric cases. METHODS: Routine bone marrow smears assay and enzyme labeling
      for micromegakaryocytes with CD41 monoclonal antibody (McAb) were performed in 46
      children with ITP. The level of platelet-associated immunoglobulin (PA-Ig) was
      measured with ELISA. RESULTS: Among 46 children, 36 had acute ITP (AITP)and 10
      chronic ITP (CITP). The number of megakaryocytes increased or was normal in 45
      patients, but decreased only in 1 case of CITP. The positive rate of
      micromegakaryocytes and type I micromegakaryocytes was 98% (45/46) and 35%
      (16/46), respectively. The positive rate of type I micromegakaryocytes was higher
      in CITP (50%) cases than that in AITP (31%) cases, but the median of the other
      three types of micromegakaryocytes in CITP cases (159) was lower than that in the
      AITP cases (336). There was no relationship between the numbre of all types of
      megakaryocytes and the level of PA-Ig. CONCLUSION: Majority of patients with ITP
      showed an increase in micromegakaryocytes, especially in type II, III and IV. The
      immune disturbance might not be the only reason for ITP. The abnormality of
      quality of megakaryocytes might be one of the potential causes for
      thrombocytopenia in some cases of ITP, especially in those of CITP. The
      appearance and the number of type I micromegakaryocytes might reflect the
      prognosis of cases of ITP.

PMID- 15144716
TI  - [Long-term effect of repeated febrile convulsions on seizure susceptibility in
      immature rats].
AB  - OBJECTIVE: To elucidate the long-term effect of repeated febrile convulsions (FC)
      on seizure susceptibility in immature rats. METHODS: Warm-water-immersion rat FC
      model was developed with SD rats 22 days of age, 15 attacks of seizures were
      induced in the rats every other day, and some of the rats were left un-stimulated
      for 3 months, then were re-stimulated. Seizure phenomenon was observed, including
      the latency and the duration of seizures and the temperature of rats. Hippocampal
      neuron loss and mossy fiber sprouting were detected by thionine staining and Timm
      staining. RESULTS: After the 15th bath, the latency, the duration of seizures,
      and the temperature of rats were respectively (4.3 +/- 0.8) min, (5.5 +/- 2.9)
      min, (42.2 +/- 0.7) degrees C. Three months later, on re-stimulation, in 14 of 19
      rats with previous FC experience seizures occurred while in only one of 13 non-FC
      rats seizure occurred and lasted for 8.5 min. Three months later, the latency,
      the duration of seizures, and the temperature of rats were respectively (5.4 +/-
      0.6) min, (19.3 +/- 5.1) min, and (42.4 +/- 0.4) degrees C (4 rats with status
      epileptics were not included). The incidence of seizures on re-stimulation in
      rats of FC group (74%) was significantly higher than that in non-FC group (8%)
      (chi(2) = 13.50, P < 0.01), and the duration of seizures [(19.3 +/- 5.1) min] was
      significantly longer than those induced in early life [(5.5 +/- 2.9) min] (t =
      10.49, P < 0.01). After the 15th bath, no significant change was demonstrated in
      rats of different groups. While 3 months later, prominent neuron loss was
      observed in hippocampal CA(3) region in rats with previous FC experience (P <
      0.01). Significant mossy fiber sprouting phenomenon was detected after the 15th
      bath and 3 months later (P < 0.05). CONCLUSION: Repeated FC in early life
      enhances long term susceptibility of rats to seizure.

PMID- 15144715
TI  - [Heparanase expression of peripheral blood cells in steroid responsive nephrotic
      syndrome patients].
AB  - OBJECTIVE: The beta-D-endoglycosidase heparanase (Hpa) is HS-specific which leads
      to the degradation of heparan sulfate (HS). An increased permeability of the
      glomerular basement membrane (GBM) for proteinuria was suggested to relate to a
      decrease of HS side chains in the GBM. However, whether an up-regulated
      expression of Hpa exists in steroid responsive nephrotic syndrome (SRSNS) remains
      unknown. The purpose of this study was to evaluate the role of Hpa in the
      development of SRSNS and the correlation with the proteinuria. METHODS: Forty
      three children with SRSNS were selected and included the active stage group (n =
      23), the restoration stage group (n = 10) and the remission stage group (n = 10).
      There were 23 nephritic nephrosis children, 15 purpura nephritis children and 15
      healthy children as controls. By using the method of reverse transcriptase-PCR
      (RT-PCR), Hpa gene expression in the peripheral blood leukocytes (PBLs) was
      assayed. RESULTS: (1) All patients with nephrotic syndrome exhibited higher
      levels of Hpa mRNA than those of the healthy group (P < 0.05). The highest
      expression was in the active stage group of SRSNS (1.27 +/- 0.36, P < 0.001),
      while there was no difference between the patients of nephritic nephrosis group
      (0.62 +/- 0.15) and purpura nephritis group (0.55 +/- 0.17) (P > 0.05). (2) In
      contrast with the healthy group, there was a significant difference in the active
      stage group of SRSNS (P < 0.001). So was the restoration stage group (P < 0.05),
      but there was no difference to the remission stage group (P > 0.05). (3) There
      was a positive correlation between the expression level of Hpa mRNA and the
      quantity of urinary protein (r(s) = 0.751, P < 0.001). CONCLUSION: Up-regulated
      expression of Hpa mRNA may be important to the loss of glomerular negative charge
      in GBM and lead to proteinuria in SRSNS.

PMID- 15144717
TI  - [Effects of aminoguanidine in different dosages on renal function in endotoxin
      induced rabbits shock model].
AB  - OBJECTIVES: To explore the effects of aminoguanidine (AG) in different dosages on
      renal function in endotoxin induced rabbits shock model in the early stage and to
      approve the effects of dose-depended and time-depended of AG. METHODS: Fourty New
      Zealand rabbits under anaesthesia were randomly divided into 5 groups: sham
      group, LPS group, the first group of AG, the second group of AG, the third group
      of AG. Each rabbits from the four groups received Escherichia Coli O55B5 LPS 400
      micro g/kg to induce endotoxic shock except sham group. Edotoxic shock was
      diagnosed when the mean arterial pressure (MAP) decreased to 30%. Each rabbits in
      sham group and LPS group received 5ml NS, in the other three groups were infused
      with AG 30 mg/kg (the first group of AG), 50 mg/kg (the second group of AG), 100
      mg/kg (the third group of AG) in 5ml NS, respectively. Urine output was recorded
      at the following time points, before injecting IPS (T(0)), shock (T), 1 h (T(1)),
      2 h (T(2)), 3 h (T(3)), 4 h (T(4)), 5 h (T(5)) and 6 h (T(6)) after shock. Plasma
      nitrate and nitrite (NO(3)(-)/NO(2)(-), stable products of NO), BUN, Scr, RBP
      were determined at the time points of T, T(2), T(4) and T(6). RESULTS: LPS
      increased NO(3)(-)/NO(2)(-), BUN, Scr, RBP [from (47 +/- 5) micro mol/L, (5.8 +/-
      1.5) mmol/L, (41 +/- 10) micro mol/L, (240 +/- 61) ng/L (T(0)) to (160 +/- 18)
      micro mol/L, (15.5 +/- 1.8) mmol/L, (166 +/- 23) micro mol/L, (1580 +/- 180) ng/L
      (T(6)), respectively, P < 0.01]; Urine output decreased significantly [from (17.6
      +/- 2.8) ml (T(0)) to (1.3 +/- 0.6) ml (T(6)), P < 0.01]. AG attenuates the
      increasing of NO(3)(-)/NO(2)(-), BUN, Scr and RBP, and decreasing of urine
      output. NO(3)(-)/NO(2)(-) of the first, second and third group of AG at T(6) were
      (58 +/- 8), (50 +/- 14) and (46 +/- 9) micro mol/L, respectively. Compared to LPS
      group, there was a significant difference (P < 0.01). BUN was (8.2 +/- 2.9), (7.5
      +/- 1.9) and (5.5 +/- 1.8) mmol/L, respectively at T(6). Compared to LPS group,
      there was a significant deference (P < 0.01). RBP was (350 +/- 60), (272 +/- 72)
      and (248 +/- 103) ng/L, respectively at T(6) (compared to LPS group, there was a
      significant deference. P < 0.05, < 0.05, < 0.01). Urine output was (11. 1 +/-
      2.4), (12. 1 +/- 1. 3) and (17.1 +/- 2. 4) ml, respectively on T(6) (compared to
      LPS group, there was a significant deference, P < 0.01). AG of 100 mg/kg showed
      the best effect among three AG groups. CONCLUSION: AG inhibited NO formation in
      dose-depended and time depended way. AG attenuated the changes of renal function
      induced by NO.

PMID- 15144718
TI  - [Angiogenesis and its regulatory factors in brain tissue of neonatal rat hypoxic
      ischemic encephalopathy].
AB  - OBJECTIVE: To investigate possible mechanism of angiogenesis in brain tissue of
      neonatal rat hypoxic-ischemic encephalopathy (HIE). METHODS: Forty seven-day old
      neonatal rats were randomly assigned to hypoxic-ischemic (Model group) or sham
      treatment (Sham group), each group had 20 rats. Five rats from each group were
      sacrificed on days 1, 3, 7 and 14 after hypoxia-ischemia. Paraffin sections of
      the brain were stained with anti-endothelial cell, anti-proliferating cell
      nuclear antigen (PCNA) or anti-vascular endothelial growth factor (VEGF) by using
      single or double immunohistochemistry. The brain capillary density index (BCDI),
      brain proliferating capillary density index (BPCDI) and the expression of VEGF
      were analyzed under the microscope. The expression of VEGF and hypoxia-inducible
      factor-1alpha (HIF-1alpha) mRNA in hypoxic-ischemic side of the brain was
      measured by RT-PCR. RESULTS: BCDI around infarct brain tissue in the model group
      began to rise on day 3 and remained higher than that of the sham group from day 3
      to day 14 [day 3: (9.80 +/- 1.05)/HPF vs. (4.90 +/- 0.66)/HPF, P < 0.01;day 14:
      (13.29 +/- 3.90)/HPF vs. (6.08 +/- 1.50)/HPF, P < 0.01]. Occasional proliferating
      capillary was found in brain tissue of normal neonatal rats. The density of
      proliferating brain capillary on day 3 and day 7 of Model group [(0.54 +/-
      0.15)/HPF vs. (0.90 +/- 0.25)/HPF] were significantly higher than those of Sham
      group [(0.12 +/- 0.05)/HPF vs. (0.13 +/- 0.07)/HPF, P < 0.01]. VEGF was mainly
      expressed in the cytoplasm of neurons, capillary endothelial cells and pial
      cells. Viable neurons and endothelial cells in the infarct areas also expressed
      VEGF. The expression of VEGF mRNA in hypoxic-ischemic brain tissue was
      significantly higher than that of normal control (P < 0.01) and temporally
      preceded angiogenesis. The expression of VEGF mRNA at 12 hours of HIE model was
      significantly higher than that of normal control (1.56 +/- 0.27 vs. 0.95 +/-
      0.21, P < 0.05). It reached its peak on day 1 and day 3 (1.85 +/- 0.31 vs. 1.86
      +/- 0.39), significantly higher than that of normal control (P < 0.01), and
      decreased by day 7 and day 14, without significant difference compared with
      normal control (P > 0.05). The expression of HIF-1alpha mRNA was also up
      regulated after hypoxic-ischemic treatment. The expression of HIF-1alpha mRNA
      (1.07 +/- 0.21) was significantly higher than that of normal control (0.64 +/-
      0.28, P = 0.048) at 3-hour of HIE model, reached its peak on day 1 (1.73 +/-
      0.42, P < 0.01), remained at high expression level on day 3 (1.44 +/- 0.36, P <
      0.05) and began to decline by day 7 and day 14 when it was not significantly
      different from normal control. CONCLUSIONS: Angiogenesis exists in the brain
      tissue of neonatal rat HIE model. Up-regulation of VEGF expression mediated by
      HIF-1 may play an important role in the process of angiogenesis.

PMID- 15144719
TI  - [The change of glomerular pathology in children with steroid resistant
      nephropathy].

PMID- 15144720
TI  - [Evaluation of silent myocardial ischemia by adenosine triphosphate-atropine
      stress echocardiography in children with Kawasaki disease].

PMID- 15144721
TI  - [Predominant tubulointerstitial lupus nephritis in a case].

PMID- 15144722
TI  - [Gastric fistulation with transcutaneous endoscopy in a child].

PMID- 15144723
TI  - [Congenital rubella syndrome caused patent ductus arteriosus and atrial septal
      defect in a case].

PMID- 15144724
TI  - [Satoyoshi's syndrome in a case].

PMID- 15144725
TI  - [A new way for the treatment of pulmonary hypertension: effectiveness of
      inhalation of nebulized NO donor].

PMID- 15144726
TI  - [Progress in researches on L-asparaginase targeted to childhood leukemia].

PMID- 15144727
TI  - [Advances in bronchopulmonary dysplasia].

PMID- 15144728
TI  - Involvement of nitric oxide in fading of 5-hydroxytryptamine-induced
      vasocontraction in rat isolated vena portae smooth muscle.
AB  - PURPOSE: The aim of the present study was to investigate a nitric oxide (NO)
      involvement in the mediation of a 5-HT-induced vasoconstrictions response in the
      rat portal vein in vitro. MATERIAL AND METHODS: Isolated rat portal vein
      preparations obtained after dissection were placed in organ baths for isometric
      force measurement via a strain gauge. RESULTS: 5-hydroxytryptamine (5-HT) in
      concentrations ranging from 3x10(-8) M to 3x10(-4) M contracted portal vein
      preparations (EC50= 7x10(-7) M) in a concentration dependent manner. The
      vasoconstrictions induced by 5-HT was significantly increased in endothelium
      denuded vessels. Pre-treatment with N(omega)-nitro-L-arginine methyl Ester (L
      NAME 100 microM) enhanced the contractive response to 5-HT either in intact- or
      denuded endothelium vessels. Whereas, ketanserin (0.1 microM) abolished 5-HT
      induced vasoconstrictions (EC50= 4.6x10(-8) M). Furthermore, a non-selective 5-HT
      receptors agonist, sumatriptan, (1x10(-10 )M - 1x10(-5) M) induced a reduction of
      spontaneous rhythmic contractions either in endothelium-intact or in endothelium 
      denuded vessels. However, 5-HT-induced vasoconstriction was unaffected by
      propranolol (10 microM). CONCLUSIONS: These findings are consistent with the
      hypothesis that the vasoconstrictor activity of 5-HT in vascular smooth muscle
      was mediated by activation of 5-HT1B/D and 5-HT2B receptors subtypes involving
      the endothelium (NO) dependent mechanism.

PMID- 15144729
TI  - Effect of a lipoidic excipient on the absorption profile of compound UK 81252 in
      dogs after oral administration.
AB  - PURPOSE: Effect of caprylocaproyl macrogolglycerides (Labrasol), as a lipoidic
      excipient/vehicle in an oral capsule formulation, on pharmacokinetic disposition
      of a BCS Class 3 compound, UK-81252, was investigated in vivo in a canine model.
      METHODS: The control and lipoidic formulations were administrated to six Beagle
      dogs in a crossover, single dose design with a 2-week washout period in between
      treatments. The plasma concentration-time profile for the lipoidic formulation
      was compared to that of the control formulation (lactose-based oral capsule).
      RESULTS: Although the lipoidic formulation resulted in a markedly increased oral
      bioavailability (based on mean pharmacokinetic parameters, AUC(0-48 hr) and
      C(max) ), a double-peaking phenomenon was observed with this formulation. The
      most likely cause of this double-peak effect was the gastric emptying retardation
      attribute of the lipoidic vehicle/excipient. The initial peak (Tmax1) was due to
      the absorption enhancing properties of the lipoidic formulation and the second
      peak (Tmax2) was most likely the result of a shutdown in gastric emptying for a
      period of up to 2 hours (this value varied between dogs) after which the
      remaining Compound UK 81252 emptied from the stomach to generate the second peak.
      CONCLUSIONS: Caprylocaproyl macrogolglycerides enhanced the absorption of
      Compound UK 81252. After oral administration, the liquid-filled formulation
      consistently produced a double-peak phenomenon in the plasma profile. Labrasol
      was determined to be the most likely culprit for this double peaking phenomenon.

PMID- 15144731
TI  - Definition of a novel atomic index for QSAR: the refractotopological state.
AB  - PURPOSE: In this work, a novel descriptor of atoms in molecules is introduced.
      The Refractotopological State Index for atoms (R-state,R), rectifies the atomic
      refractivity values reported by Crippen et al with the atomic refractivity values
      of the topological environment of each skeletal atom in the molecule. METHOD: The
      R-state (R(i)), for atom i is an hybrid index that is defined as the intrinsic
      refractivity value of the atom i (AR(i)) plus a perturbation term Delta AR(i) in
      the non-hydrogen depleted graph. RESULTS: The variations of the R values in
      different molecules are showed. QSAR examples previously reported by other
      authors are given for benzimidazole inhibition of Lee strain flu virus and
      receptor binding affinity of beta-carbolines. CONCLUSIONS: The index does not
      only describe the representation of the atomic dispersive forces related to the
      molar refractivity but also the influence of bounded and unbounded atoms as a
      measure of the distance-effect of the other groups in the molecule. The R-state
      index has proved a good performance, either alone or combined with the electro
      topological (E)-state index. This implies that in those cases this representation
      of dispersive forces between the molecule and the active site is a valid approach
      to the biological problem

PMID- 15144730
TI  - Biliary excretion of irinotecan and its metabolites.
AB  - PURPOSE: The aim of this study was to investigate the excretion of irinotecan
      hydrochloride (CPT-11) and its metabolites into the gastrointestinal lumen via
      the biliary route after intravenous administration of lactone and carboxylate
      forms of CPT-11. METHODS: Biliary excretions of CPT-11 and its metabolites, SN-38
      and SN-38-glucuronide, were investigated by an in vivo administration study using
      rats. The biliary excretion profiles for both the lactone and carboxylate forms
      of CPT-11 and its metabolites were determined. RESULTS: After the i.v. injection
      of the lactone form of CPT-11, the cumulative biliary excretion of SN-38
      glucuronide was much greater than that of CPT-11 and SN-38, and biliary excretion
      of SN-38 was less than that of CPT-11. Further, CPT-11 and SN-38 were mainly
      excreted into bile as carboxylate forms. After the administration of the CPT-11
      carboxylate form, biliary excretion of SN-38-glucuronide was significantly
      smaller than that after the administration of CPT-11 lactone form. On the other
      hand, biliary excretion of CPT-11 and SN-38 was greater after dosing with the CPT
      11 carboxylate form than that after the CPT-11 lactone form. CONCLUSIONS: The
      results suggest that the rate of conversion of lactone to carboxylate forms of
      CPT-11 and its metabolites plays a major role in the biliary excretion of these
      compounds.

PMID- 15144732
TI  - Systemic bone formation with weekly PTH administration in ovariectomized rats.
AB  - PURPOSE: Weekly subcutaneous administration of 0 (vehicle), 10 and 80 microg/kg
      doses of human parathyroid hormone (1-34) [PTH (1-34)] were compared based on
      their capacity to induce systemic formation of bone in 9 month-old ovariectomized
      (OVX) Sprague-Dawley rats. METHODS: Changes elicited at bone tissue after 4 weeks
      of treatment were assessed using dual x-ray absorptiometry, micro-computed
      tomography (microCT), and ashing. RESULTS: The 10 microg/kg dose led to a
      significant increase (p<0.025) in femoral bone mineral density (BMD) over vehicle
      and 80 microg/kg-treated groups. Similarly, structural analysis of the femoral
      neck trabecular bone by microCT revealed increases in bone volume fraction and
      trabecular thickness over the pre-treatment baseline, and vehicle- and 80
      microg/kg-treated groups. CONCLUSIONS: The data suggest that the weekly
      administration of 10 microg/kg of PTH (1-34) was sufficient to significantly
      promote the bone mineral density systemically. The weekly administration of 10
      microg/kg over a 4-week treatment period is, to our knowledge, one of the lowest
      reported total dose of PTH (1-34) shown to induce a net anabolic effect on
      skeletal tissue in OVX rats.

PMID- 15144734
TI  - Hepatic disposition of cyclosporine A in isolated perfused rat livers.
AB  - PURPOSE: To develop an isolated perfused rat liver model to study the hepatic
      disposition of cyclosporine A (CyA) in both sexes. METHODS: Livers were isolated
      from male (n = 6) and female (n = 7) rats and perfused with a physiological
      buffer in a single-pass manner. A bolus 1-mg dose of CyA was injected into the
      inlet catheter and periodical samples (0-15 min) were collected from the outlet
      perfusate. The concentrations of CyA in the outlet perfusate, collected bile (0
      15 min), and liver tissue (at the end of perfusion) were quantitated by HPLC and
      subjected to statistical moment analysis. RESULTS: The dilution curves of CyA in
      the outlet perfusate exhibited unusually long terminal phases due to large volume
      of distribution of the drug (approximately 100 mL/g) and its slow release from
      binding sites in the liver (net release rate constant of approximately 0.020 min(
      1)). This was in contrast to the rapid uptake of the drug, indicated by
      significant amounts of the intact drug (>40%) taken up during one single pass
      through the liver. Consequently, the liver tissue:perfusate distribution ratio of
      CyA was very high (approximately 220). No significant differences were found
      between the male and female livers in any of the estimated parameters.
      CONCLUSIONS: The tissue binding of cyclosporine A is substantial, slowly
      reversible, and gender-independent in isolated perfused rat livers.

PMID- 15144733
TI  - In vitro cytotoxicity studies of hydrogel pullulan nanoparticles prepared by
      AOT/N-hexane micellar system.
AB  - PURPOSE: The purpose of this study was to prepare crosslinked pullulan
      nanoparticles encapsulating bioactive molecules inside the aqueous core of
      Aerosol-OT/n-hexane reverse micellar droplets with narrow size distribution for
      drug and gene delivery applications. METHODS: The nanoparticles have been
      characterised by various physico-chemical methods such as dynamic light
      scattering (DLS), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), loading capacity and in vitro release behaviour in aqueous
      buffer. The influence of these nanoparticles on human dermal fibroblasts in vitro
      has been assessed in terms of cell adhesion, cytotoxicity and light microscopy.
      RESULTS: Size distribution studies using DLS and TEM show that the particles are
      spherical in shape with size of 42.0+/-2.5 nm diameter. Release of FITC-Dex from
      nanoparticles increased with time with 75% of dye released in 6 hours, while only
      40% of the dye was released in the initial 2 hours. Results from cell
      adhesion/viability assay suggest that the pullulan nanoparticles are non-toxic to
      cells and do not cause any distinct harm to cells. Fibroblasts were healthy and
      maintained their morphology and adhesion capacity. CONCLUSIONS: These studies
      indicated that these nanoparticles have further merit as possible carriers for
      genes and nucleotide drugs for intracellular delivery.

PMID- 15144735
TI  - Assessment of enzymatic cleaning agents and disinfectants against bacterial
      biofilms.
AB  - PURPOSE: Microbial biofilm has become difficult to control by antibiotic and
      biocide regimes that are effective against suspended bacteria. Their colonization
      of surfaces can be a problem and is generally controlled through cleaning and
      disinfection. This study was undertaken to examine the efficacy of the
      disinfectants including Bio-Ow, Econase CE, Gamanase GC 140, IndiAge 44L,
      Mannanase AMB, Multifect P-3000, Neutrase, Pandion, Paradigm, Pectinex Ultra SP
      L, Promozyme, Resinase A2X, Spezyme AA300, Spezyme GA300 and Vinozym EC, and the
      proteinase against bacterial biofilms. METHODS: The effectiveness of 20
      commercial disinfectants against Pseudomonas aeruginosa (P. aeruginosa) biofilms
      using a fluorometric technique was examined. Additionally the disinfectants were
      also tested against Lactobacillus bulgaricus (L. bulgaricus), Lactobacillus
      lactis (L. lactis) and Streptococcus thermophilus (S. thermophilus) isolates
      using microtitration tray based turbidimetric techniques. Escherichia coli (E.
      coli) was used as the test bacteria in the fluorometric control method. RESULTS:
      Among the first group of the enzymatic cleaning agents tested, four disinfectants
      (Pandion, Resinase A2X, Spezyme GA300 and Paradigm) were the most potent against
      bacterial biofilms after 30 min incubation time (residual bacterial count less
      than 10(3) CFU (colony forming units)/ml). However, only Resinase A2X and
      Paradigm showed a good effect on bacterial biofilms after 15 min incubation time.
      Proteinase disinfectants (alkalase, chymotrypsin, cryotin and krilltrypsin) from
      the second group of the disinfectants showed a good effect against P. aeruginosa
      biofilm when tested in the absence of milk. The performance of the disinfectants
      was reduced in the presence of milk. The minimum inhibitory concentration (MIC)
      of the cleaning agents was determined as the lowest concentration inhibiting
      bacterial growth. The MIC was tested on Lactobacillus bulgaricus (L. bulgaricus),
      Lactobacillus lactis (L. lactis) and Streptococcus thermophilus (S. thermophilus)
      isolates. The minimum inhibitory concentrations (MIC) for Paradigm against S.
      thermophilus and L. Lactis were lower than L. Bulgaricus. Whereas, the MIC of
      Pandion against L. bulgaricus was lower than MIC against L. lactis. Resinase A2X
      had no inhibitory effect on bacterial growth when the concentration was less than
      or equal to 2.4 mg/ml and Spezyme GA 300 concentration less than or equal to 7.3
      mg/ml. Minimum inhibitory concentration of Pandion against L. bulgaricus was 2.7
      microg/ml and against L. lactis 5.3 microg/ml. Growth of S. thermophilus was
      inhibited in all concentration of Pandion tested. CONCLUSIONS: The choice of
      disinfectant or cleaning agent along with the optimum concentration and the time
      of action is very important when destroying microbes. It is also important that
      the resistances of microbes to different disinfectants and cleaning agents be
      taken into account when planning the cleaning process

PMID- 15144736
TI  - Antinociceptive effects of Peganum harmala L. alkaloid extract on mouse formalin
      test.
AB  - PURPOSE: To evaluate the effect of Peganum harmala (Syrian rue) a wild-growing
      flowering plant belonging to the family Zygophylaceae and found abundantly in
      Iran on formalin-induced pain response in mice. METHODS: Total alkaloid extract
      was prepared from dry seeds of Peganum harmala. All doses of extract were
      dissolved in normal saline and administered intraperitoneally 30 minutes before
      formalin injection to the mouse paw. Nociception was recorded 0-5 (early phase,
      A) and 15-40 (late phase, B) minutes after formalin injection. The alkaloid
      extract was subjected to silica gel column chromatography using a linear gradient
      with a CHCl3-MeOH system and different fractions collected. The effective
      fraction in formalin test were further purified and isolated by preparative thin
      layer chromatography (TLC) and identified on the basis of nuclear magnetic
      resonance (NMR) and mass spectrometry (MS) analysis. RESULTS: Alkaloid extract in
      doses (mg/kg) used induced significant reduction in pain response when compared
      to control as follow: 16 (28.63%), 20 (59.15%), 24 (80.75%), 28 (90.14%) and 30
      (100%) in the early phase and 20 (24.67%), 24 (59.93%), 28 (78.52%) and 30 (100%)
      in late phase. Observed responses in both phases of A and B were dose-dependent
      with r2 of 0.93 and 0.99 respectively. ED50 for phases of A and B were 27.87 and
      24.63 mg/kg respectively (p<0.001 for all groups). CONCLUSION: Harmaline, the
      last step of extraction is the main effective antinociceptive agent of the
      Peganum harmala alkaloid extract.

PMID- 15144737
TI  - Studies on anti-diarrhoeal activity of Calotropis gigantea R.Br. in experimental
      animals.
AB  - PURPOSE: Calotropis gigantea R. Br. (Asclepiadaceae) a wildly growing plant has
      been reported to possess number of medicinal properties and other purposes. The
      purpose of the present study was to evaluate scientifically the anti-diarrheal
      effects of C. gigantea used traditionally in Indian system of medicine using
      castor oil-induced diarrhoea model. METHODS: The anti-diarrheal effect of
      hydroalcoholic (50:50) extract of aerial part of Calotropis gigantea was studied
      against castor oil-induced-diarrhea model in rats. The gastrointestinal transit
      rate was expressed as the percentage of the longest distance traversed by the
      charcoal divided by the total length of the small intestine. The weight and
      volume of intestinal content induced by castor oil were studied by enteropooling
      method. RESULTS: Like atropine (3 mg/kg, i.p.) there were significant reductions
      in fecal out put and frequency of droppings when the plant extracts of 200 and
      400 mg/kg doses were administered intraperitoneally compared with castor oil
      treated rats. All doses of the plant extracts also significantly retarded the
      castor-oil induced enteropooling and intestinal transit. The dose 100 (P<0.01),
      200 and 400 mg/kg significantly inhibited (P<0.001) weight and volume of
      intestinal content. CONCLUSIONS: The remarkable anti-diarrheal effect of
      C.gigantea extract against castor oil-induced diarrhea model attests to its
      utility in a wide range of diarrheal states

PMID- 15144738
TI  - Antinociceptive effects of the essential oil of Dracocephalum kotschyi in the
      mouse writhing test.
AB  - PURPOSE: Dracocephalum kotschyi is a wild-growing flowering plant belonging to
      the family Labiatae and found abundantly in Iran. This plant has been used in
      Iran folk medicine as analgesic. METHODS: The Dracocephalum kotschyi essential
      oil was isolated and studied on writhing test a visceral pain model in mice.
      Different constituents of the essential oil were determined by gas chromatography
      mass spectrophotometry technique. RESULTS: Limonene, verbenone, alpha-terpineol,
      perillyl alcohol and caryophyllene were the major constituents of the essential
      oil. The essential oil in doses (mg kg-1) used 12.5 (13.9%, P<0.05), 25 (43.1%,
      P<0.01), 50 (68.7%, P<0.01), 75 (39.8%, P<0.01) induced significant reduction in
      pain response when compared to control. The ED50 was 61.61 mg kg(-1). Hyoscine (1
      mg kg(-1)) and indomethacin (5 mg kg(-1)) induced significant (P<0.01) reductions
      (74.9% and 76.7% respectively) in pain response in comparison to control.
      CONCLUSION: This study confirms that antinociceptive properties of D. kotschyi
      are comparable to those of hyoscine and indomethacin used. Presence of limonene
      and alpha-terpineol might be responsible for antinociceptive properties of this
      essential oil. Further studies are necessary to find out a place for it in
      antispasmodic therapies in human

PMID- 15144739
TI  - Evaluation of anti-hyperglycemic activity of some novel monocyclic beta lactams.
AB  - PURPOSE: The present study was undertaken to examine the effect of monocyclic
      beta-lactams (compounds 5a-5o) for anti-hyperglycemic activity against alloxan
      induced diabetes in rats. As these compounds have been shown to control
      disturbances in cholesterol metabolism induced by diabetes. METHODS: The test
      compounds were synthesized via [2+2] cycloaddition (Staudinger) reaction of
      imines with ketenes. The anti-hyperglycemic effect of test compounds was
      evaluated in alloxan-induced diabetes in rats by monitoring their effect on blood
      glucose and liver glycogen contents. RESULTS AND DISCUSSION: In the diabetic
      rats, high glucose levels and depression in hepatic glycogen contents were
      observed which could be attributed to the less availability of active form of
      enzyme glycogen synthetase. Test compounds significantly lowered the serum
      glucose levels indicating their anti-hyperglycemic activity. This activity of
      test compounds may be due to increased utilization of glucose as indicated by
      decreased serum glucose levels and an increase in the activity of glycogen
      synthetase enzyme as evidenced by rise in liver glycogen contents in test groups.
      Based on the results structure activity relationship (SAR) has been discussed and
      favorable substitutions around of monocyclic beta-lactam have been reported.
      Present study concluded that these compounds could have potential anti
      hyperglycemic effect, which might be due to increased utilization of glucose
      either through increased insulin activity or induction of glycogen synthetase
      enzyme. CONCLUSION: Present study concluded that these compounds have significant
      anti-hyperglycemic effect. Further studies are required to reveal the mechanism
      of action.

PMID- 15144740
TI  - Stability of sulfadiazine oral liquids prepared from tablets and powder.
AB  - PURPOSE: To assess the stability of sulfadiazine (SDZ) oral liquids prepared from
      tablets and powder at two temperatures. METHODS: Solutions of SDZ 200 mg/mL were
      prepared from commercially available 500 mg tablets and powder in sterile water
      for irrigation. They were stored in amber glass bottles at 4 degrees C and 23
      degrees C. The concentrations of SDZ were determined in duplicate by high
      performance liquid chromatography at 0, 1, 3, 7 and 14 days. The initial and
      final pH of solutions was compared. The recovery of SDZ from tablets was
      determined. A loss exceeding 10% of the initial concentration of SDZ was
      considered excessive degradation. RESULTS: The recovery of SDZ from tablets was
      100 +/- 3%. The initial pH values were significantly different between solutions
      prepared from tablets and powder, 6.9 and 9.8 respectively. No significant
      difference was found between initial and final pH values for the two all
      formulations. Detectable change in odor was observed for the solutions stored at
      23 degrees C. The solution prepared from powder was stable 3 days stored at 4
      degrees C. Other formulations lost over 10% of the initial SDZ concentration
      within 2 days. CONCLUSIONS: SDZ 200 mg/mL oral solution prepared from powder
      could be used to facilitate drug administration to very young children by nurses
      but by taking account of its fast degradation.

PMID- 15144741
TI  - Fluorometric variable-temperature kinetics investigations of the
      transesterification reaction of procaine with aliphatic alcohols.
AB  - PURPOSE: Variable-Temperature Kinetics has been used to obtain the rate constants
      of the reaction at various temperatures during one kinetic run. METHODS: Pseudo
      first-order rate constants for the transesterification of procaine with aliphatic
      alcohols ethanol, n-propanol and tert-butanol were obtained by the fluorescence
      spectroscopy using the variable-temperature kinetics (VTK) method. RESULTS: The
      activation parameters of the reactions were calculated (24-28 kcal x mol(-1)).
      The half-life of the procaine decreases in the ethanol solution compared with the
      other alcoholic solutions in the presence of sodium ethoxide. CONCLUSIONS: The
      investigation time of the reactions is reduced to one-tenth of the one used for
      usual kinetic methods.

PMID- 15144742
TI  - [Mortality of myocardial infarction in the PRIMVAC registry. Prognostic factors].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine the mortality
      due to acute myocardial infarction in the coronary units from Comunidad
      Valenciana (Spain) and the prognostic factors associated with a higher mortality.
      PATIENTS AND METHOD: Demographic characteristics, coronary risk factors,
      electrocardiographic ischemic signs, complications and mortality of patients with
      acute myocardial infarction admitted in the coronary units were collected. The
      study period comprised January 1995-December 1999. Death incidence was measured
      during coronary unit's stay. Factors associated with poor prognosis were
      analyzed. RESULTS: 10.213 patients entered into the study. Mean age at admission
      was 65 12 years. 23.8% were females (76.2% males). Global mortality in coronary
      units was 13.3%. Independent variables associated with higher mortality were (p <
      0.05): advanced age (OR=1.06 [1.05-1.06]), female sex (OR=1.45 [1.26-1.66]),
      diabetes mellitus (OR=1.53 [1.35-1.74]), previous myocardial infarction (OR=1.46
      [1.23-1.70]), previous angor pectoris (OR=1.29 [1.13-1.49]) and Q-wave infarction
      (OR=1.23 [1.03-1.43]). Factors associated with lower mortality were:
      hypercholesterolemia (OR=0.76 [0.66-0.78]), smoking (OR=0.65 [0.57-0.74]) and
      thrombolysis (OR=0.85 [0.78-0.92]). CONCLUSIONS: At present, in the reperfusion
      therapy era, acute myocardial infarction has a high mortality after coronary unit
      admission. Several clinical factors are associated with a worse prognosis.

PMID- 15144744
TI  - [Rate of infection by blood-borne viruses in active heroin users in 3 Spanish
      cities].
AB  - BACKGROUND AND OBJECTIVE: The objective of this paper was to determine the
      prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV),
      hepatitis B virus (HBV) and human T lymphotropic virus (HTLV) infections in
      active heroin users in Spain. SUBJECTS AND METHOD: A cross-sectional study was
      carried out in 440 heroin users in three different urban areas of Spain:
      Barcelona, Madrid, and Seville. Specimens were analyzed for the presence of anti
      HIV, anti-HCV, anti-HBc, and anti-HTLV antibodies. RESULTS: The rate of anti-HIV
      antibodies was 20% (CI 95%, 16.3-23.7%); anti-HBc: 21.4% (CI 95%, 17.5-25.2%);
      anti-HCV: 59.1% (CI 95%, 54.5-63.7%); and anti-HTLV (HTLV-II in all cases): 3.4%
      (CI 95%, 1.7-5.1%). Barcelona and Madrid had similar rates for each virus, yet
      these were lower in Seville especially with regard to HCV (Barcelona: 59.7% [CI
      95%, 53.1-66.3%]; Madrid: 63.8% [CI 95%, 56.7-70.9%]; Seville: 41.8% [CI 95%,
      28.8-54.9%]). CONCLUSIONS: HCV is the most prevalent infection among active
      heroin users in Spain. The rate of infection by blood-borne viruses is higher in
      Madrid and Barcelona than in Seville (notably for HCV), most likely due to a
      lower rate of intravenous users in this city.

PMID- 15144743
TI  - [Sex differences in mortality at one-month and at one-year after an acute
      coronary syndrome].
AB  - BACKGROUND AND OBJECTIVE: We aimed to delineate the sex differences in short-term
      (one-month) and long-term (one-year) cardiac death after an acute coronary
      syndrome. PATIENTS AND METHOD: After the publication of the new myocardial
      infarction definition, we prospectively analyzed 1,324 consecutive patients
      admitted with a diagnosis of acute coronary syndrome to a tertiary hospital. 483
      (37%) of these patients had myocardial infarction with ST-elevation, 439 (33%)
      had myocardial infarction without ST elevation (troponin I > 1 ng/ml) and 402
      (30%) had an unstable angina (troponin I < 1 ng/ml). RESULTS: Within 1-year of
      follow-up, 177 deaths (13.4%) were detected. There was a similar rate of cardiac
      death in female and male patients with 'non-ST elevation myocardial infarction'
      (one-month: 9.7% vs 7.1%, p = NS; one-year: 16.7% vs 13.2%, p = NS) and with
      unstable angina (one-month: 3% vs 1.9%, p = NS; one-year: 3% vs 5.6%, p = NS).
      Among patients with 'ST-elevation myocardial infarction' women showed a higher
      rate of cardiac death at one-month (21.5% vs 9.8%; p < 0.0001) and at one-year
      (28.9% vs 14.1%, p < 0.0001) than men. In the multivariate analysis, independent
      predictors of cardiac death in 'ST-elevation myocardial infarction' at one-year
      were age > 70 years (p < 0.0001), Killip class > 1 (p < 0.0001) and lack of
      reperfusion (p = 0.003) but not having a female sex. CONCLUSIONS: Patients with
      'non-ST elevation acute coronary syndromes' did not display sex differences with
      regard to mortality. Women with 'ST-elevation myocardial infarction' had a higher
      mortality; however, these differences were not independently related to a female
      sex but to a worse baseline clinical profile and a lesser rate of reperfusion.

PMID- 15144745
TI  - [Chronic urticaria and Helicobacter pylori].
AB  - BACKGROUND AND OBJECTIVE: We intended to analyze the influence of Helicobacter
      pylori eradication on the clinical evolution of patients with chronic idiopathic
      urticaria. PATIENTS AND METHOD: The evolution of dermatological symptoms after
      eradication was studied in a group of 55 patients previously diagnosed with
      chronic idiopathic urticaria who were infected by Helicobacter pylori. RESULTS:
      There was a partial or complete improvement in 74.6% (CI 95%, 61-85%) of studied
      patients. We could not demonstrate a statistically significant influence of sex,
      age or endoscopic lesions on the clinical evolution of urticaria after
      eradication. CONCLUSIONS: These results suggest a possible usefulness of
      Helicobacter pylori eradication in some patients with chronic idiopathic
      urticaria. Controlled and randomized studies are necessary to confirm it.

PMID- 15144746
TI  - [Female gender and mortality after myocardial infarction].

PMID- 15144747
TI  - [Methods to perform economic assessments of health interventions].

PMID- 15144748
TI  - [Blood pressure goals in diabetes. A critical appraisal].
AB  - In this article we review the evidence supporting the need to achieve a target
      blood pressure (BP) under 130-80 mm Hg in diabetic patients, as recent
      international guidelines recommend (JNC VII, ESH-ESC and ADA). We have analyzed
      the explicit arguments used in these guidelines, 3 clinical trials designed to
      determine which is the best BP in diabetics (HOT, UKPDS-38 and ABCD) as well as
      other potentially misleading clinical trials. In our opinion, neither these 3
      specific clinical trials nor other trials quoted in the guidelines (due to
      results and methodology employed) can answer the question of the best goal of
      pharmacological treatment for hypertension in diabetics. On the other hand,
      international agreements are not sufficiently rigorous regarding both the sources
      mentioned and the direct interpretation of the data provided. We conclude that
      there is not enough evidence to support the goal pressure below 130/80 mm Hg in
      patients with diabetes. We insist in the need of individualization of therapy in
      patients and consider that a under 140/85 mm Hg goal pressure in diabetics is
      perfectly supported by current evidence.

PMID- 15144749
TI  - [Primary prevention of acute myocardial infarction with aspirin].

PMID- 15144750
TI  - [Atypical form of late neurosyphilis].

PMID- 15144751
TI  - [Thalidomide in the treatment of recurrent plasmocitomas in an HIV-infected
      patient].

PMID- 15144752
TI  - [Combined cardiorenal failure: a lesson of clinical practice].

PMID- 15144753
TI  - [Diffuse pulmonary hemorrhage as a complication of treatment with use of platelet
      glycoprotein IIb/IIIa receptor inhibitors after coronary stent implantation].

PMID- 15144754
TI  - [REGICOR better than Framingham coronary risk function in Spain: good news for
      our patients].

PMID- 15144756
TI  - [Adult isolated noncompactation cardiomyopathy].

PMID- 15144757
TI  - Gendered communication among young people in Mexico: implications for sexual
      health interventions.
AB  - Effective communication between partners is crucial for good sexual health, but
      is often difficult to achieve. This qualitative study shows how gendered
      communication can act as an important barrier to successful dialogue between men
      and women. Both content and manner of speaking are often gendered: not only can
      topics of conversation be socially defined as more or less appropriate for a
      speaker according to his or her sex, but men and women can also differ
      systematically in terms of the phrases and words they use. This may lead to a
      lack of the common forms of expression that are needed for effective
      communication. The study examines communication about sexuality among young men
      and women in low-income areas of Mexico City. The relationship between gender
      stereotypes of sexual behaviour and the gendered nature of communication
      strategies is explored. The negative consequences of gendered communication for
      effective dialogue between men and women are illustrated. Interventions that can
      enhance communication between men and women would be expected to have a positive
      impact on sexual health. This paper argues that research and interventions
      intended to improve sexual health may instead inadvertently reinforce
      communication barriers not only by failing to address the social pressures that
      exacerbate gendered communication, but also more insidiously, by using language
      that actively contributes to these pressures. An example of an intervention that
      avoids this problem is the Mexican programme "Gente Joven" ("Young People").

PMID- 15144758
TI  - Risks, stigma and Honduran Garifuna conceptions of HIV/AIDS.
AB  - The HIV/AIDS epidemic along Honduras' north coast has intensified in recent years
      and become particularly severe in Garifuna communities. Based on a qualitative
      study in the community of Las Espinas and comparison with results from an earlier
      knowledge, attitudes, beliefs and practices survey, this article explores
      Garifuna ideas about the disease, focusing on issues of risk perception and
      stigma. Using correspondence analysis with data from systematic elicitation
      techniques we abstract the local schema of HIV/AIDS, showing how accurate
      knowledge of transmission co-occurs with cultural judgments about safe partners,
      increasing chances for infection. Despite broad familiarity with the disease in
      the community it remains highly stigmatized, suggesting continuing problems in
      coming to terms with the epidemic as treatment becomes more widely available in
      Honduras. Questions of power, sexuality and affective expectations about partners
      complicate the situation for women hoping to prevent infection. Given the broader
      risk environment characterized by labor migration and transnational movement,
      vital interventions and educational efforts in Garifuna communities will need to
      be complemented with prevention efforts in contexts where men make a living.

PMID- 15144759
TI  - Socio-cultural influences on young people's sexual development.
AB  - Emerging evidence indicates that the mechanisms that create health (or ill
      health) at the population level exist at the intersection between the individual
      and more "upstream" forces that shape our social contexts. To investigate this
      proposition, we collected detailed descriptions of youth's perceptions about the
      socio-cultural and other structural aspects of their contexts that shape their
      sexual behaviour patterns, and ultimately their health outcomes. In this paper,
      we examine how social context shaped experiences and perceptions pertaining to
      sexual behaviour among 18-24 year olds living in two Canadian communities (one
      rural and one urban). We investigate explanations for the struggle that youth
      engage in as they attempt to situate their emergent sexual behaviour patterns
      within community, family, peer, and broader social contexts. Two central
      processes appeared to be important to the experiences of youth in the current
      study and their recollections about their adolescent sexual experiences. These
      processes are embedded in social norms and structures and are directed at
      pathologizing sex and silencing meaningful discussion about sex. Together, they
      interact to create a climate of sex-based shame. The findings of this qualitative
      study add to previous sociological and feminist research that has also
      demonstrated how traditional approaches to understanding youth sexual behaviour
      tend to ignore or discount the "embeddedness" of young people in their social
      structures and contexts.

PMID- 15144760
TI  - "Viagra stories": challenging 'erectile dysfunction'.
AB  - Medical approaches to sexual difficulties prioritise the physical aspects of
      sexuality over other aspects, locating 'disorders' primarily in the anatomy,
      chemistry or physiology of the body. In accordance with this perspective on
      sexual matters, physicians look to physical interventions (for example, hormones,
      drugs, and surgery) to treat any 'abnormalities'. Following the discovery of
      popular--and profitabl-e-sexuopharmaceuticals such as sildenafil citrate (Viagra)
      for the treatment of erectile difficulties affecting men, the medical model has
      gained increasing influence in the domain of sexual health and well-being.
      However, while medical definitions of--and interventions related to--sexual
      difficulties are underpinned by an understanding of a 'universal' body (that is,
      an essential biological body that transcends culture and history), and by the
      categorisation of the normal and the pathological, the accounts of users of
      Viagra, and their sexual partners, do not necessarily support such
      understandings. In some cases, the experiences and perspectives of those affected
      by erectile difficulties directly challenge the reductionist model of sexuality
      and sexual experience espoused by medicine. In this paper, we report on a New
      Zealand study investigating the socio-cultural implications of Viagra, involving
      33 men and 27 women discussing the impact of erectile difficulties and Viagra use
      within relationships. The diverse experiences of participants are discussed in
      relation to two key issues: the notion of 'sexual dysfunction' itself; and the
      idea of drugs such as Viagra acting as a 'quick fix' for sexual difficulties
      affecting men. We argue that the existence of a range of Viagra 'stories'
      disrupts a simplistic mechanistic portrayal of the male body, male sexuality and
      'erectile disorder'.

PMID- 15144761
TI  - A critical review of behavioral issues related to malaria control in sub-Saharan
      Africa: what contributions have social scientists made?
AB  - In 1996, Social Science & Medicine published a review of treatment seeking for
      malaria (McCombie, 1996). Since that time, a significant amount of socio
      behavioral research on the home management of malaria has been undertaken. In
      addition, recent initiatives such as Roll Back Malaria have emphasized the
      importance of social science inputs to malaria research and control. However,
      there has been a growing feeling that the potential contributions that social
      science could and should be making to malaria research and control have yet to be
      fully realized. To address these issues, this paper critically reviews and
      synthesizes the literature (published, unpublished and technical reports)
      pertaining to the home management of illness episodes of malaria in sub-Saharan
      Africa from 1996 to the end of 2000, and draws conclusions about the use of
      social science in malaria research and control. The results suggest that while we
      have amassed increasing quantities of descriptive data on treatment seeking
      behavior, we still have little understanding of the rationale of drug use from
      the patient perspective and, perhaps more importantly, barely any information on
      the rationale of provider behaviors. However, the results underline the dynamic
      and iterative nature of treatment seeking with multiple sources of care
      frequently being employed during a single illness episode; and highlight the
      importance in decision making of gender, socio-economic and cultural position of
      individuals within households and communities. Furthermore, the impact of
      political, structural and environmental factors on treatment seeking behaviors is
      starting to be recognised. Programs to address these issues may be beyond single
      sector (malaria control programme) interventions, but social science practice in
      malaria control needs to reflect a realistic appraisal of the complexities that
      govern human behavior and include critical appraisal and proposals for practical
      action. Major concerns arising from the review were the lack of evidence of
      'social scientist' involvement (particularly few from endemic countries) in much
      of the published research; and concerns with methodological rigor. To increase
      the effective use of social science, we should focus on a new orientation for
      field research (including increased methodological rigor), address the gaps in
      research knowledge, strengthen the relationship between research, policy and
      practice; and concentrate on capacity strengthening and advocacy.

PMID- 15144762
TI  - Cost-effectiveness of malaria control interventions when malaria mortality is
      low: insecticide-treated nets versus in-house residual spraying in India.
AB  - Malaria is one of the leading causes of morbidity and mortality in the developing
      world and a major public health problem in India. Disillusioned by in-house
      residual spraying (IRS), and increasingly aware that insecticide-treated nets
      (ITNs) have proved to be effective in reducing malaria mortality and morbidity in
      various epidemiological settings, policy-makers in India are keen to identify
      which is the more cost-effective malaria control intervention. A community
      randomised controlled trial was set up in Surat to compare the effectiveness and
      efficiency of IRS and ITNs. Both control strategies were shown to be effective in
      preventing malaria over the base-case scenario of early diagnosis and prompt
      treatment. The mean costs per case averted for ITNs was statistically
      significantly lower (Rs. 1848, 1567-2209; US$ 52) than IRS (Rs. 3121, 2386-4177,
      US$ 87). The incremental cost-effectiveness ratio for ITNs over IRS was Rs. 799
      (US$ 22). The conclusions were robust to changes in assumptions. This study
      expands the scope of recent comparative economic evaluations of ITNs and IRS,
      since it was carried out in a low mortality malaria endemic area.

PMID- 15144763
TI  - A comparison of breast, testicular and prostate cancer in mass print media (1996
      2001).
AB  - This paper compares the portrayal of breast, testicular and prostate cancer in
      mass print English language magazines in the United States and Canada from 1996
      to 2001. It is a follow-up of three papers that examined each of these three
      diseases separately in high circulating magazines up to 1995. It includes both
      quantitative and qualitative analyses of magazine stories and notes the
      continuing dominance of a medical perspective regarding disease as well as the
      association of each type of cancer examined with stereotypically individualized
      yet feminine and masculine characteristics and pursuits. It notes the conflation
      of breast cancer, since the discovery of BRCA1 and BRCA2, with the family. To be
      a 'feminine' woman is to be vulnerable to breast cancer and to be a 'masculine'
      man is to be vulnerable to testicular cancer when young and prostate cancer when
      older. The association of disease not just with personhood but also with the
      specifics of stereotyped masculinity and femininity may construct a more
      intimate, more personal link between disease and identity. This close attachment
      of gender and disease may shore up and exacerbate a fear reaction. It may also
      serve to diminish the awareness of other, more prevalent, causes of death for men
      and women. The social control consequences of potentially exacerbated disease
      specific fear are discussed.

PMID- 15144765
TI  - Gender and physical violence.
AB  - This study examines incidents of physical violence in relation to the sex of both
      assault victim and attacker. A survey of all assault victims attending an urban
      accident and emergency department (AED) in Norway during a 2-year period was
      carried out. All the assault victims were interviewed using a structured
      questionnaire administered by the attending physician as part of the initial
      consultation at the AED. During this interview, information about the victims,
      the attackers and the assaults was collected from the victims. Information on the
      sex, age, alcohol state of victims, and any referral to hospitals and
      specialists, was collected from the victim's medical notes at the AED. The
      severity of the victim's injuries was rated retrospectively using Abbreviated
      Injury Scale (AIS) and Shepherd's Injury Severity Scale for rating of injuries of
      assault. A total of 1234 men (74%) were attacked by other men, 354 women (21%)
      were attacked by men, 33 men (2%) by women, and 59 women (4%) by other women. The
      characteristics of the assaults carried out amongst female victim-female attacker
      and male victim-male attacker groups had many similarities. The same was found
      for the female victim-male attacker and male victim-female attacker groups. We
      conclude that changes in the traditional behaviour associated with women and men
      in relation to physical violence may be taking place.

PMID- 15144764
TI  - Accommodating risk: responses to BRCA1/2 genetic testing of women who have had
      cancer.
AB  - The relationship between risk awareness and anxiety has been the subject of
      extensive theoretical debate and empirical research. Previous studies of women
      with a family history of hereditary breast and ovarian cancer suggest that both
      healthy at-risk women and former cancer patients report increased anxiety upon
      learning about their increased risks of developing these diseases. Indeed,
      anxiety about genetic risks has been reported as influencing decisions about DNA
      testing and risk-reducing surgery on healthy breasts and ovaries. This
      qualitative study of women who had been treated for breast/ovarian cancer
      investigated their perceptions of, and reactions to, their genetic risks of
      developing further cancers following genetic testing (BRCA1/2 mutation
      searching). In-depth interviews were undertaken with 30 women (10 mutation
      carriers, 8 awaiting a result and 12 who received an inconclusive test result).
      Whilst the majority of women in all three groups adopted a fatalistic approach
      with regard to their future health and did not regard their genetic risks as a
      threat to self, a few reported heightened anxiety on learning they were at
      increased risk of developing a second primary cancer. The data suggest that
      affected women understand their genetic risks of cancer within the context of
      their previous disease experiences. It is observed that women's responses to
      their genetic risk are influenced by the degree to which they have accommodated
      their risk status in their biography following their diagnosis and treatment of
      cancer.

PMID- 15144766
TI  - "Social thinking" and cultural images: teenagers' notions of tobacco use.
AB  - The health hazards of tobacco use are well-known, and it is considered
      particularly important to prevent tobacco use among teenagers. New generations of
      teenagers still start using tobacco. To develop a more profound understanding of
      tobacco use among teenagers, the purpose of this study is to explore
      representations of tobacco use, smoking as well as snuffing, at the age when
      young people often start using tobacco. Focus-group interviews were carried out
      with 14-15 year olds in two schools in the Stockholm area. The analysis reveals
      that teenagers are well informed about the health-hazards of tobacco use. At the
      same time they hold complex and conflicting ideas concerning the relationship
      between tobacco use, risk, the body and "human nature". At the most general level
      of "social thinking" there is a dynamic relation between the three main
      representations of tobacco use related to: (1) notions of risk, (2) "human
      nature" and; (3) society's efforts to discipline its citizens, which together can
      be seen as the social representation of tobacco use. These representations of
      tobacco use are discussed as related to the teenagers' identity-work and gender
      identities.

PMID- 15144767
TI  - Using a point system in the management of waiting lists: the case of cataracts.
AB  - In the management of waiting lists, point systems could be a useful mechanism to
      establish priorities amongst patients. In this paper we explore the possibility
      of using Conjoint Analysis (CA) in order to implement a point system based on
      social preferences. We conducted an experiment for the specific case of cataract
      extraction. In spite of the pilot nature of the study the results seems to
      suggest that CA is a feasible method in order to estimate a point system.

PMID- 15144768
TI  - Social capital, the miniaturisation of community and self-reported global and
      psychological health.
AB  - Social capital is often operationalised as social participation in the activities
      of the formal and informal networks of civil society and/or as generalised trust.
      Social participation and trust are two aspects of social capital that mutually
      affect each other, according to the literature. In recent years there has been an
      increased attention to the fact that generalised trust decreases for every new
      birth cohort that reaches adulthood in the USA, while social participation may
      take new forms such as ideologically much narrower single-issue movements that do
      not enhance trust. The phenomenon has been called "the miniaturisation of
      community". The effects of similar patterns in Sweden on self-reported health and
      self-reported psychological health are analysed. The odds ratios of bad self
      reported global health are highest in the low-social capital category (low-social
      participation/low trust), but the miniaturisation of community and low-social
      participation/high-trust categories also have significantly higher odds ratios
      than the high-social capital category (high-social participation/high trust). The
      odds ratios of bad self-reported psychological health are significantly higher in
      both the low-social capital category and the miniaturisation of community
      category compared to the high-social capital category, while the low-social
      participation/high-trust category does not differ from the high-social capital
      reference group.

PMID- 15144769
TI  - Physical well-being and school enrollment: a comparison of adopted and biological
      children in one-child families in China.
AB  - Adoption has increased in China since 1980 when the government started the one
      child policy. There were approximately six million adopted children living in
      China in 1988. The objective of this study was to compare adopted and biological
      children in one-child families across a number of measures of physical well-being
      and school enrollment. The 1992 National Sample Survey on the Situation of
      Children provided data on 2458 adopted and 194,760 biological children aged 0-14
      years living in one-child families. Logistic regression models were used to
      adjust for confounders. We found that adopted children were not significantly
      different from biological children in reported diarrhea and nutritional outcomes
      (stunting, underweight, wasting) after controlling for other known demographic,
      socioeconomic and geographic correlates. However, there was evidence of
      significantly higher odds of never being immunized and not being currently
      enrolled in school, and evidence of slightly lower odds of having fever or acute
      respiratory infections among adopted children compared to biological children.
      These results suggest that adopted children were as healthy and well-fed as
      biological children, but adopted children aged 7-14 years were less likely to be
      enrolled in school than biological children.

PMID- 15144770
TI  - Present concerns of survivors of human rights violations in South Africa.
AB  - Most research on persons subjected to physical torture for political reasons has
      framed this experience as traumatic, with the sequelae approximating the
      diagnostic criteria of posttraumatic stress disorder (PTSD). However, responses
      to checklists, questionnaires, and structured interview schedules may reflect the
      effect of demand characteristics more than the actual concerns of respondents.
      Thus semi-structured qualitative interviews were conducted with 20 South Africans
      who were detained for political reasons during the apartheid era. The interviews
      were transcribed and analyzed with the assistance of the Atlas.ti 4.5 programme.
      Results showed that the major concerns expressed by the sample were somatic
      problems, economic marginalization, non-clinical emotional distress, and
      dissatisfaction with the present political dispensation in South Africa.
      Respondents also expressed concerns that reflected symptoms of traumatization,
      but these were not salient in comparison with the other themes that emerged.
      These data suggest that a model of trauma and the diagnostic category of PTSD may
      be less appropriate than suggested by most of the literature in accounting for
      the concerns of many South African former political detainees. This paper
      critiques the hegemony of the psychiatric model of traumatization in
      conceptualizing the needs of this population, and suggests an alternate
      perspective that is broader and more inclusive than a psychiatric paradigm. It
      also discusses the research and possible clinical implications of the results in
      terms of addressing the needs of former detainees in South Africa.

PMID- 15144771
TI  - Authorizing tradition: vectors of contention in Highland Maya midwifery.
AB  - In Guatemala, midwives deliver the majority of children and play an important
      health care role in rural areas. Maya midwives, using time-proven methods, are
      the chief providers of care for mothers and infants in these areas. In recent
      decades, however, the medical establishment has become interested in Maya
      midwives, and is currently engaged in training and certifying many of them. This
      study examines how Guatemalan health authorities have sought to change Maya
      midwifery, refashioning its vocational framework and retooling it in accordance
      with Western medical principles. I focus on the place of obligatory formal
      training and the use of biomedical materials in the experience of Kaqchikel Maya
      midwives, and consider how the health officials employ these means to undermine
      the midwives' knowledge base. Encounters between midwives and formal health
      personnel reveal an ongoing privileging of biomedical knowledge, one that
      preserves asymmetrical relationships between these practitioners. This creates an
      environment favorable to health personnel, and helps them to extend their
      influence through the midwives into the community. Given this, I contend that
      health personnel value local Maya midwives primarily for their role in furthering
      the goals of biomedicine.

PMID- 15144772
TI  - Turning the tide: benefit finding after cancer surgery.
AB  - Post-traumatic growth and benefit finding after adverse life events are emerging
      topics in stress and coping research. This study examined personal and social
      resources of cancer patients and their perception of positive life changes as a
      consequence of illness. In addition, the mediating role of coping strategies
      (acceptance and social comparison) was investigated. One month after tumor
      surgery, 105 cancer patients completed measures of social support and self
      efficacy. Coping was assessed half a year after surgery, while benefit finding
      was examined 12 months post-surgery. Correlational and path analyses showed a
      link between personal resources (self-efficacy) as well as social resources
      (received social support) and benefit finding. The effect of self-efficacy
      disappeared when coping was specified as a mediator between the resources and
      benefit finding. Social support retained a direct effect on benefit finding. The
      results emphasize the predictive quality of resources for recovery and adjustment
      after surgery and the mediating role of coping. Findings are discussed with
      regard to recent developments in the study of post-traumatic growth.

PMID- 15144773
TI  - Environmental antimicrobial contamination from terraccumulation and diffuse
      pollution pathways.
AB  - The fate of antimicrobial pharmaceuticals entering the aquatic environment has
      become an increasing concern for researchers and regulators in the past decade,
      and recent research has focused on antimicrobial contamination from point
      sources, such as wastewater treatment facility outfalls. Terraccumulation is the
      concentration of pollutants in soils from land application of contaminated
      biosolids generated by agricultural practices and water and wastewater
      facilities. The terraccumulation of antimicrobials and mobility in diffuse
      pollution pathways should not be overlooked as a contributor to the spread of
      bacterial resistance and the resulting threat to human drug therapy. This review
      critically examines recent global trends of bacterial resistance, antimicrobial
      contaminant pathways from agriculture and water treatment processes, and the need
      to incorporate diffuse pathways into risk assessment and treatment system design.
      Alignment of environmental scientific and engineering research with strategies
      applied in clinical situations could contribute to continued efficacy of
      antimicrobial therapies necessary for human health and welfare.

PMID- 15144774
TI  - Integrating decision tools for the sustainable management of land contamination.
AB  - The approach to taking decisions on the management of land contamination has
      changed markedly over 30 years. Change has been rapid with policy makers and
      regulators, practitioners and researchers having to keep pace with new
      technologies, assessment criteria and diagnostic methods for their measurement,
      techniques for risk analysis and the frameworks that support decision-makers in
      their efforts to regenerate historically contaminated land. Having progressed
      from simple hazard assessment through to 'sustainability appraisal' we might now
      consider piecing together the experience of decision-making for managing land
      contamination. Here, we critically review recent developments with a view to
      considering how better decisions can be made by integrating the decision tools
      available. We are concerned with the practicality of approach and the issues that
      arise for practitioners as decision criteria are broadened.

PMID- 15144776
TI  - Modeling and simulation of point-non-point source effluent trading in Taihu Lake
      area: perspective of non-point sources control in China.
AB  - The past decades have witnessed some efforts in point source water pollution
      controls in China. However, adequate abatement efforts have not been implemented
      on non-point source control, and non-point source contributions remain and have
      increased as a share of surface water degradation. It has been noted that
      conventional command-and-control regulations are ineffective for agricultural non
      point source pollution, and watershed abatement trading between point and non
      point sources may serve as a cost-effective way to deal with it. In this paper,
      the feasibility of point-non-point sources effluent trading in China and cost
      effectiveness of the trading system on water pollution control are evaluated
      using a stochastic programming model and a combined probabilistic watershed
      simulation of a representative agricultural watershed in the Taihu Lake area. The
      method and model can be used to assess economic and environmental opportunities
      of trading in similar watersheds in China. The use of explicit emission target
      and reliability decision rules in the chance-constrained programming model is a
      practical simplification to convert a stochastic program into a solvable
      deterministic problem. Based on the simulation, suggestions on development and
      implementation of point-non-point sources abatement trading scheme in China were
      discussed.

PMID- 15144775
TI  - Regional increase of mean chloride concentration in water due to the application
      of deicing salt.
AB  - The Directive of the European Parliament and of the Council 2000/60/EC:
      Establishing a Framework for Community Action in the Field of Water Policy,
      states that it is necessary to consider human activities within a river basin in
      order to prevent and reduce the spreading of pollutants and to achieve good water
      status. This paper shows a simple method to estimate the environmental pressure
      from the deicing of roads as steady state chloride concentration in water. The
      data processed are presented using GIS. The result showed that the contribution
      of deicing salt is of importance for the chloride concentration on a regional
      scale. The increase in chloride concentration is also compared to the background
      concentration and other sources of chloride within the river basin. Road salt
      applied by the Swedish National Road Administration (SNRA) accounts for more than
      half of the total chloride load for the river basin investigated. The method
      presented may easily be generalised to a national scale for monitoring the
      environmental effects of deicing salt application.

PMID- 15144777
TI  - Pulmonary fibre burden in sheep living in the Biancavilla area (Sicily):
      preliminary results.
AB  - In a national survey on mortality from malignant pleural neoplasms in Italy,
      aimed at detecting geographic clusters of cases of the disease, the town of
      Biancavilla, located in a volcanic area of Eastern Sicily, showed high risk of
      pleural mesothelioma in the absence of occupational asbestos exposure. An
      environmental survey suggested the stone quarries located in 'Monte Calvario',
      south-east of the town of Biancavilla, as a possible source of asbestiform fibre
      exposure. A subsequent crystal-chemistry investigation of the 'Monte Calvario'
      amphiboles identified the mineral asbestiform fibres as 'fluoro-edenite', a new
      end-member of the edenite ==> fluoro-edenite series. A collaborative
      epidemiological and environmental study was initiated to investigate the
      characteristics of the outbreak of malignant mesothelioma and test the hypothesis
      of a causal association with exposure to naturally occurring fibres. To
      investigate if a sheep population could be used to monitor the environmental
      diffusion of the fibres, we examined lung specimens from 27 culled sheep, at
      least 3 years old and living near Monte Calvario to check for the presence of
      fluoro-edenite fibres, using scanning electron microscopy (SEM) analysis and X
      ray microanalysis. Fourteen mineral species have been isolated in the mineral
      particulate matter taken from pulmonary parenchyma, and fluoro-edenite was
      detected in eight sheep. These preliminary data suggest a possible bio-indicative
      role of sheep as sentinel animals in the evaluation of environmental fibre
      diffusion, which merits further investigation.

PMID- 15144778
TI  - The population genetic structure of Littorina littorea (Mollusca: Gastropoda)
      along a pollution gradient in the Scheldt estuary (The Netherlands) using RAPD
      analysis.
AB  - The population genetic structure of the periwinkle Littorina littorea was
      analysed using random amplified polymorphic DNA (RAPD). Three primers, coding for
      six putative polymorphic loci were surveyed to infer the genetic structure of
      seven populations located along the heavily polluted Western (i.e. in order of
      decreasing pollution load W1, W2, W3 and R1) and the relatively clean Eastern
      Scheldt (E1, E2 and E3) estuary (The Netherlands). A genetic distance based UPGMA
      (Unweighted pair group method with arithmetic mean) dendrogram revealed an
      estuary-related structuring, as Eastern and Western Scheldt sites formed two
      separate clusters. The Western Scheldt cluster was, however, much more
      heterogeneous, with three RAPD loci revealing a significant genetic heterogeneity
      compared to none when the Eastern Scheldt sites were compared. Overall mean
      heterozygosity levels were high, but did not reveal a difference between the
      estuaries. The current data (1) confirm the patterns of variation previously
      observed with electrophoretic analyses of esterases and (2) strongly support that
      these patterns of variation have a genetic basis, in the presence of intense gene
      flow. In addition, it is suggested that selection, rather than bottleneck
      effects, induced by the less favourable living conditions at W1, W2 and W3 are
      responsible for the genetic patterning.

PMID- 15144779
TI  - Geographical variation and partition of metals in tissues of Octopus vulgaris
      along the Portuguese coast.
AB  - Zinc, Cu, Cd, Pb and Hg were determined in mantle, arm and digestive gland of 59
      individuals of Octopus vulgaris captured at six sites along the Portuguese coast.
      Metal concentrations in tissues did not vary significantly (P<0.05) with
      size/weight, sex or sexual stage. The abundance of metals in each analysed tissue
      was: Zn>Cu>>Cd>Pb>Hg. Concentrations in the digestive gland reached one (Pb, Hg)
      and two (Zn, Cu, Cd) orders of magnitude higher than those found in arm and
      mantle, which indicates that the digestive gland contains the major storage sites
      for these elements, acting as a detoxification organ. However, concentrations in
      the digestive gland showed contrasting geographic patterns: Zn, Pb, Cu and Hg
      were higher in the Southern stations, while Cd levels increased drastically in
      Northern stations. This increase is in line with the contrasting Cd distribution
      in coastal waters. The lack of relations between metal concentration in tissues
      and biological parameters facilitates the recognition of those spatial patterns.
      The geographical contrast of Cd is extended to the accumulation in mantle and
      arm. A possible explanation for these enhanced values is that threshold level for
      Cd accumulation in digestive gland was attained and detoxification processes
      eventually modified.

PMID- 15144780
TI  - Chemical inhibition of PCDD/F formation in incineration processes.
AB  - This review summarises results of our pilot-scale experiments to find suitable
      inhibitors for preventing the formation of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/F) during waste incineration and to specify the role of the
      main factors affecting the inhibition process, and is based on doctoral
      dissertation of Ruokojaarvi (2002). Results of previous experiments reported by
      other researchers are also presented and compared with ours. The detailed aims of
      our experiments were (1) to compare the effects of different inhibitors on PCDD/F
      formation during incineration in a pilot plant, (2) to investigate the role of
      the particle size distribution of the flue gas on the inhibition of PCDD/Fs, and
      (3) to find the main parameters affecting PCDD/F inhibition in waste
      incineration. Prevention of the formation of PCDD/Fs with chemical inhibitors and
      the effects of different supply points, feed temperatures and process parameters
      were studied in a pilot scale incinerator (50 kW) using light heating oil and
      refuse-derived fuel as test fuels. Various concentrations of the gaseous
      inhibitors (sulfur dioxide, ammonia, dimethylamine and methyl mercaptan) were
      sprayed into the flue gases after the furnace, in addition to which urea was
      dissolved in water and injected in at different concentrations. The residence
      time of the flue gas between the furnace and the PCDD/F sampling point was varied
      in the tests. In another set of urea tests, urea-water solutions at three
      concentrations were mixed with the RDF prior to incineration. PCDD/F and
      chlorophenol concentrations, together with other flue gas parameters (e.g.
      temperature, O2, CO, CO2 and NO), were analysed in the cooling flue gases. The
      gaseous and liquid inhibitors both notably reduced PCDD/F concentrations in the
      flue gas, the reductions achieved with the gaseous inhibitors varying from 50 to
      78%, with dimethyl amine the most effective, while that produced with urea was up
      to 90%. The PCDD/F reductions were greater at increased inhibitor concentrations
      and with increased residence time of the flue gas between the furnace and the
      sampling point. PCDD/F concentrations in the particle phase decreased much more
      markedly than those in the gas phase. The urea inhibitor did not alter the
      particle size distribution of the PCDD/Fs when the amount of inhibitor was
      adequate. Chemical inhibitors seem to offer a very promising technique for
      preventing the formation of PCDD/Fs in waste incineration. The addition of urea
      to the fuel before combustion proved to be very effective approach and could be a
      useful technique even in the full-scale incinerators.

PMID- 15144781
TI  - Characterization and implication of potential fugitive dust sources in the Paso
      del Norte region.
AB  - A series of analyses were performed to provide chemical signatures for surface
      soils and to evaluate potential sources of fugitive dust in the Paso del Norte
      (PdN) region. Eighteen sites were selected for soil sampling based on an
      assessment of the soil types in the region and the main upwind source areas with
      a potential for wind erosion. Analyses of the soil samples provided chemical
      'fingerprints' of the surface soil that are presumed responsible for much of the
      fugitive dust loading in the region. Analysis of chemical data through
      multivariate statistical techniques combined with information on lithologic
      units, soil types, and enrichment factors identified several groups of elements
      associated with either natural or anthropogenic origins. Cluster analysis and
      principal components analysis defined four groups of elements while a redundancy
      analysis implied a strong association between certain elements (Ag, As, Cd, Mo,
      Mn, Pb, Sb) and an anthropogenic point source in the region. The conclusions from
      the statistical analyses are further supported by the enrichment factor (EF)
      analysis, using aluminum as the reference element. That is, a group of presumed
      anthropogenic trace elements had their highest EFs in the fine size fraction at a
      site close to the anthropogenic point source. Thus, the statistical analyses of
      surface soil data provide a useful means for quantifying the extent of
      anthropogenic perturbations and for highlighting some implications of
      contaminated fugitive dust sources.

PMID- 15144782
TI  - Metal concentrations in soils around the copper smelter and surrounding
      industrial complex of Port Kembla, NSW, Australia.
AB  - Anthropogenic emissions of metals from sources such as smelters are an
      international problem, but there is limited published information on emissions
      from Australian smelters. The objective of this study was to investigate the
      regional distribution of heavy metals in soils in the vicinity of the industrial
      complex of Port Kembla, NSW, Australia, which comprises a copper smelter,
      steelworks and associated industries. Soil samples (n=25) were collected at the
      depths of 0-5 and 5-20 cm, air dried and sieved to <2 mm. Aqua regia extractable
      amounts of As, Cr, Cu, Pb and Zn were analysed by inductively coupled plasma mass
      spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry
      (ICP-AES). Outliers were identified from background levels by statistical
      methods. Mean background levels at a depth of 0-5 cm were estimated at 3.2 mg/kg
      As, 12 mg/kg Cr, 49 mg/kg Cu, 20 mg/kg Pb and 42 mg/kg Zn. Outliers for elevated
      As and Cu values were mainly present within 4 km from the Port Kembla industrial
      complex, but high Pb at two sites and high Zn concentrations were found at six
      sites up to 23 km from Port Kembla. Chromium concentrations were not anomalous
      close to the industrial complex. There was no significant difference of metal
      concentrations at depths of 0-5 and 5-20 cm, except for Pb and Zn. Copper and As
      concentrations in the soils are probably related to the concentrations in the
      parent rock. From this investigation, the extent of the contamination emanating
      from the Port Kembla industrial complex is limited to 1-13 km, but most likely <4
      km, depending on the element; the contamination at the greater distance may not
      originate from the industrial complex.

PMID- 15144783
TI  - Dioxin emission factors for automobiles from tunnel air sampling in Northern
      Taiwan.
AB  - This study measured PCDD/F concentrations in tunnel air and vehicle exhaust. The
      ambient air samples were collected with air samplers (Tisch PS-1) complying with
      USEPA TO-9A. The results indicate that the tunnel air had a PCDD/F TEQ
      concentration about two times as high as that of outside air (47.3 and 57.1 fg-I
      TEQ/m3 for tunnel air vs. 37.1 fg-I-TEQ/m3 and 23.3 fg-I-TEQ/m3 for outside air,
      respectively). This provides the direct evidence that PCDD/F compounds are
      emitted from the combustion processes in gasoline- and diesel-fueled engines.
      According to the tunnel study, the emission factors ranged from 5.83 to 59.2 pg I
      TEQ/km for gasoline vehicles and 23.32 to 236.65 pg I-TEQ/km of diesel vehicles.
      This indicates that the dioxin emission factor in Taiwan is lower than that
      measured in USA, Norway and Germany. When the speed of the diesel vehicle was set
      at 40 km/h, the dioxin concentration emitted from diesel vehicle was 278 pg/m3
      (6.27 pg-I-TEQ/m3) from tailpipe testing. However, when the diesel vehicle was
      idled, the dioxin concentration increased greatly to 4078 pg/m3 (41.9 pg-I
      TEQ/m3). From the results of tunnel air sampling, the PCDD/Fs emission from
      automobiles in Taiwan was estimated as 3.69 g I-TEQ per year.

PMID- 15144784
TI  - Building materials as a source of PCB pollution in Bergen, Norway.
AB  - Although PCB is a globally recognised pollutant, an understanding of its
      transport from man-made building materials to the environment is poorly
      constrained. This paper presents data from a study that was conducted in order to
      determine the extent of PCB usage in plaster on building facades in the Bergen
      area, Norway. The study was to determine whether PCB concentrations vary
      according to building usage type and age. One aim was also to determine the
      nature and extent of displacement of PCB from the facade into the surrounding
      soil. Buildings built between 1952 and 1979 were chosen for the study. Three
      different media were sampled during the study; surface soil, plaster and paint.
      Samples were then analysed for PCB7 content. The results show that there is a
      difference in PCB usage in buildings of different age and usage type. Residential
      buildings and schools demonstrated higher PCB concentrations in both soil and
      plaster than buildings designated for office use, storage, or for industrial
      purposes. Buildings erected in the 1950s and 1960s also show a higher PCB
      concentration than buildings from a later date. It appears that the usage of PCB
      for these purposes decreased in the 1970s. Thirty percent of the soil samples
      showed a higher PCB concentration than the Norwegian action level. The soil
      samples tend to have a higher concentration than the corresponding plaster from
      the adjacent wall, which probably has its cause in the high soil organic matter
      contents that retains PCB. Plaster has not been considered a pollution source in
      previous studies; therefore this study demonstrates a new source that needs to be
      considered in emission calculations.

PMID- 15144785
TI  - Determination of anthropogenic input of Ru, Rh, Pd, Re, Os, Ir and Pt in soils
      along Austrian motorways by isotope dilution ICP-MS.
AB  - A joint study with the Federal Environment Agency of Austria was carried out to
      determine the distribution of Ru, Rh, Pd, Os, Ir and Pt (PGE) and Re in soils
      along major motorways. Emphasis was put on Ir as to date little is known about
      its anthropogenic input as this metal is now also used in automobile catalytic
      converters. Soil samples were analysed by ICP-MS through online-coupling of a
      chromatographic column to separate the PGEs from interfering matrix constituents.
      At all sampled sites not only Rh, Pd and Pt but also Ir and Re significantly
      exceed natural background values; concentrations reached 13 ng/g, 25 ng/g, 134
      ng/g, 1.1 ng/g and 9.8 ng/g, respectively. The analytical procedure proved to be
      very selective and sensitive and, therefore applicable to routine soil analysis.

PMID- 15144786
TI  - Mercury emissions from selected stationary combustion sources in Korea.
AB  - Mercury emissions from various stationary combustion sources such as coal-fired
      power plants, oil-fired power plants, industrial utility oil boilers, iron
      manufacturing plants, and industrial waste incinerators, were measured. The US
      EPA (Environmental protection agency) method 101A and the Ontario hydro method
      were used to sample the mercury containing combustion flue gases, at the inlet of
      the air pollution control devices (APCDs) and at the stack. Collected samples of
      both gaseous and particulate forms were then analyzed using CVAA (cold vapor
      atomic absorption) type analyzer. Measurement results from the coal-fired power
      plant showed percentages of elemental mercury (Hg0) as high as 31.4% and as low
      as 9.5%. However, the content of Hg0 was in the range of 1.3-3.7% from the
      industrial waste incinerator. Differences in mercury speciation from various
      stationary combustion sources are believed to be coming from: (1) difference in
      the fuel types; (2) difference in the major flue gas compositions (ex. HCl and
      SOx); and (3) difference in the types of air pollution control devices (APCDs).
      When the measurement results obtained using different sampling methods were
      compared, the Ontario Hydro Method gave a slightly higher mercury concentration
      measurement than that of the US EPA Method 101A.

PMID- 15144787
TI  - Processes, dynamics and modelling of radiocaesium cycling in a chronosequence of
      Chernobyl-contaminated Scots pine (Pinus sylvestris L.) plantations.
AB  - In a large forested area affected by the Chernobyl radioactive fallout,
      especially in CIS, the lasting recycling of radiocaesium (137Cs) by the trees is
      a source of long-term contamination of woody products. The quantitative
      description of the 137Cs dynamics in contaminated forest is a prerequisite to
      predictive modelling and further management of such territories. Three even-aged
      mono-specific Scots pine stands (17, 37 and 57 years old) were selected in a
      contaminated woodland in southeastern Belarus to constitute an adequate
      chronosequence. We determined the potassium and radiocaesium annual fluxes
      involved in the biological cycling in each stand using a well-documented
      calculation methodology. Qualitatively, 137Cs was shown to be rapidly recycled in
      trees through the same pathways as K and to redistribute similarly between the
      tree components. Compared to K, a higher fraction of 137Cs, corresponding to
      about the half of the annual uptake, is immobilised in perennial organs. With
      tree development, trunk wood and bark become prevailing sinks for 137Cs since
      they represent an increasing pool of biomass. In the pine chronosequence, the
      current root absorption, respectively, mobilizes 0.53, 0.32 and 0.31% year(-1) of
      the total 137Cs pool in soil. Variations in the 137Cs uptake do not reflect
      differences in the 137Cs balance between stands. In the two older stands, 51 and
      71% of the current tree contamination are related to earlier accumulation
      subsequent to the initial fallout interception and recycling. The soil is the
      dominant source of long-term tree contamination. A simple modelling based on the
      measured 137Cs fluxes indicates that, for young stands, radioactive decay
      corrected contamination would stabilize after reaching a maximum of 25 years
      after the 137Cs deposition. Stemwood presents a maximum of 15 years after the
      deposition and decrease afterwards mainly through radioactive decay. In the older
      stands, the decontamination is constant without local maximum of 137Cs level in
      the wood. The 137Cs contamination of tree components is the result of different
      influential processes like root uptake, internal translocation and
      immobilisation. For more accurate predictions, the calibration of existing models
      would be benefited by comparing with the 137Cs annual fluxes instead of the
      simple transfer factor coefficients. In the perspective of other applications,
      there is a need of such data for other radionuclides as well as for heavy metals.

PMID- 15144788
TI  - Seasonal factors controlling mineral precipitation in the acid mine drainage at
      Donghae coal mine, Korea.
AB  - Monitoring over a 12 month period in the Sanae creek flow in acid mine drainage,
      Donghae coal mine area, demonstrates that the concentrations of dissolved metals
      and sulphate are highest during autumn when water flow in the creek is at its
      lowest. The highest pH values of the stream were measured in April and May,
      whereas the lowest pH was recorded in October. The Fe concentration of stream
      water rapidly decreased downstream due to the precipitation of Fe oxyhydroxide
      and/or oxyhydroxysulfate phases in the stream. Mineral precipitates in the creek
      in the Donghae mine area show various colours such as brownish yellow (Munsell
      colour 9.5 YR hues), reddish brown (Munsell colour 3.5 YR hues) and white
      depending on seasons and distance from the pollution source in the creek. Such
      phenomena are attributed to the variation in pH and chemical composition of
      stream water caused by seasonal factors. The measured pH ranges in stream water
      of the brownish yellow, white and reddish brown precipitates are pH 3.2-4.5, 4.5
      6.0 and 5.3-6.9, respectively.

PMID- 15144789
TI  - Hydrochemical processes controlling arsenic and heavy metal contamination in the
      Elqui river system (Chile).
AB  - Severe arsenic poisoning from drinking water has been documented in Northern
      Chile. However, the Elqui River, which provides water for approximately 200,000
      people in this region, is poorly studied and no data on contaminants have been
      published to date. In this study, trace elements and the main aqueous
      constituents were monitored for approximately 2 years in the entire river system.
      Aqueous species of trace elements were determined via thermodynamic equilibrium
      calculations, and two operationally-defined suspended fractions were analyzed.
      Chalco- and arsenopyrite deposits in the upper Andes, in conjunction with mining
      and geothermal activity, were identified as exclusive point sources of heavy
      metals and arsenic. The annual input to the river system was approximately (t
      year(-1)): Fe 600, Mn 110, Cu 130, Zn 35 and As 2.0. The confluence with pH
      buffered waters in the upper river system caused collapse of iron hydroxide
      colloids and coprecipitation of all heavy metals, e.g. dissolved copper
      concentrations decreased from approximately 100 to approximately 0.2 micromol l(
      1), which is still of ecotoxic concern. The heavy metal enriched suspended solids
      settled only in the lower Elqui River. Arsenate did not adsorb to suspended
      solids and behaved strictly conservatively, exceeding the WHO guideline value for
      drinking water (0.13 micromol l(-1)) in the entire river system. Decontamination
      may be accomplished with reasonable efforts upstream in direct vicinity to the
      sources via coprecipitation, settling and appropriate pH adjustment for arsenate
      adsorption.

PMID- 15144790
TI  - Influence of methylmercury from tributary streams on mercury levels in Savannah
      River Asiatic clams.
AB  - Average methylmercury levels in five Savannah River tributary streams, sampled 11
      times over 2 years (0.170 ng/l), were nearly twice as high as in the Savannah
      River (0.085 ng/l). Total mercury levels in the tributaries (2.98 ng/l) did not
      differ significantly from the river (2.59 ng/l). All of the tributaries drained
      extensive wetlands that would be expected to support comparatively high rates of
      methylation. Mercury concentrations in Asiatic clams (Corbicula fluminea)
      collected from the discharge plumes of Savannah River tributaries (average of
      0.044 microg/g wet weight) were significantly (P<0.001) higher than in Asiatic
      clams collected from the Savannah River upstream from the tributary mouths
      (average of 0.017 microg/g wet weight). These results indicate that streams
      draining wetlands into coastal plain rivers can create localized areas of
      elevated methylmercury with resulting increases in the mercury levels of river
      biota.

PMID- 15144791
TI  - A new method of ozone forecasting using fuzzy expert and neural network systems.
AB  - This study describes the method of forecasting daily maximum ozone concentrations
      at four monitoring sites in Seoul, Korea. The forecasting tools developed are
      fuzzy expert and neural network systems. The hourly data for air pollutants and
      meteorological variables, obtained both at the surface and at the high elevation
      (500 hPa) stations of Seoul City for the period of 1989-1999, were analyzed. Two
      types of forecast models are developed. The first model, Part I, uses a fuzzy
      expert system and forecasts the possibility of high ozone levels (equal to or
      above 80 ppb) occurring on the next day. The second model, Part II, uses a neural
      network system to forecast the daily maximum concentration of ozone on the
      following day. The forecasting system includes a correction function so that the
      existing model can be updated whenever a new ozone episode appears. The accuracy
      of the forecasting system has been improved continuously through verification and
      augmentation.

PMID- 15144792
TI  - Mercury dynamics of a temperate forested wetland.
AB  - Wetlands have been identified as important sites of mercury methylation in
      catchments, but the range of wetland types and their geographic distribution for
      which methylmercury fluxes are reported in the literature are limited. Linkages
      among wetland hydrology, total mercury and methylmercury concentrations and
      fluxes, and other water quality parameters were assessed in a temperate forested
      swamp in Southern Ontario, Canada. Two hydrogeomorphically distinct stream
      reaches within the wetland exhibited differences in wetland-stream hydrologic
      connectivity, which strongly influenced mercury dynamics. Total mercury flux from
      both reaches to the downstream was highest during flow conditions in which the
      wetland and stream were hydrologically connected. The wetland as a whole was a
      net sink for total mercury and a net source for methylmercury to the downstream
      system. Both total mercury and methylmercury concentrations were related to
      dissolved and particulate organic carbon in stream waters, but these
      relationships were dependent upon the sampling location and flow conditions.
      Throughout the wetland, methylmercury concentrations exhibited temporal
      relationships with sulfate concentrations. Further, despite short surface water
      residence times, periods of wetland and stream disconnect and high pH (approx. 8)
      in surface water, methylmercury fluxes from this wetland to the downstream were
      similar to those from more stagnant and acidic wetlands.

PMID- 15144793
TI  - An X-ray diffraction (XRD) and Fourier transform infrared spectroscopic (FT-IR)
      investigation of the long-term effect on the solidification/stabilization (S/S)
      of arsenic(V) in Portland cement type-V.
AB  - The long-term effects on solidification/stabilization (S/S) of As5+-bearing
      oxyanions (AsO4(3)-) in Portland cement type-V (OPC) have been investigated by X
      ray diffraction (XRD) and Fourier transform infrared spectroscopic (FT-IR)
      techniques. The results of this study confirm our previous results that the early
      hydration of cement is inhibited by the presence of AsO4(3)-, and that the
      inhibition is mainly caused by the formation of highly insoluble Ca3(AsO4)2 on
      the surface of hydrating cement particles. Arsenate analog of ettringite
      [Ca6(Al2O6)(SO4)3 x 32H2O] was identified in the early stages of hydration of
      pure Portland cement and As(V)-treated Portland cement [OPC-As(V)], but not in 10
      year-old similar samples. The XRD and FT-IR results indicated interactions of
      oxyanions and cement particles to produce minor quantities of As5+-bearing
      compounds in fresh as well as in 10-year-old samples. New As5+-bearing phases,
      NaCaAsO4 x 7.5H2O and Ca5(AsO4)3OH were identified in the 10-year-old OPC-As(V)
      samples by XRD analyses. Based on these results it is concluded that Portland
      cement may be considered as a potential matrix to immobilize As5+-bearing wastes.

PMID- 15144794
TI  - Differentiation processes of oval cells into hepatocytes: proposals based on
      morphological and phenotypical traits in carcinogen-treated hamster liver.
AB  - Hepatic stem cells participate in the recovery process of liver with severe
      injury or impaired hepatocyte regeneration. Oval cells (an oval-shaped liver cell
      population newly emerging from the portal or periportal zones following severe
      hepatic cellular damage) are believed to be the progeny of liver stem cells and
      precursor cells of both hepatocytes and bile duct cells. An attempt was made to
      define the differentiation processes of hepatic oval cells into mature
      hepatocytes in hamsters fed a choline-deficient diet and treated with
      diethylnitrosamine and 2-acetyl aminofluorene, on the basis of histopathological,
      electron microscopical, histochemical and immunohistochemical characterization of
      hepatic cell components. Two putative differentiation pathways of oval cells
      toward mature hepatocytes are proposed, namely (1) the differentiation of
      ductular-like oval cells via ductular/acinar-type hepatocytes, and (2) the
      differentiation of individual oval cells via small hepatocytes. Those proposals
      were strongly supported by consistent immunoreactivity of the cells for OV-6, an
      oval cell marker, and differential expression patterns for CK19 and PAS-positive
      cytoplasmic glycogen granules.

PMID- 15144795
TI  - Heat shock proteins (HSPs) 27, 72 and 73 in normal and pre-ulcerative mucosa of
      the gastric pars oesophagea in swine.
AB  - Heat shock proteins (HSPs), known to play a key role in cellular homeostasis, may
      also play a role in the defensive mechanisms of gastric mucosa. By means of
      appropriate immunohistochemical and immunobiochemical techniques, the expression
      of HSP27, HSP72 and HSP73 within the epithelium of normal and pre-ulcerative
      (hyperkeratinized) mucosa of the pars oesophagea of abattoir pigs was assessed.
      In normal mucosa, HSP72 and HSP73 expression was mainly limited to the basal
      epithelial cell layer, whereas HSP27 expression was consistently detected within
      the superficial epithelial cell layers. In hyperkeratinized mucosa, HSP72 and
      HSP73 immunoreactivity appeared to be more widespread, becoming very intense
      within epithelial cells affected by hydropic degeneration. Hyperkeratinized
      mucosa also showed HSP27 immunoreactivity, which was particularly intense in
      epithelial areas affected by hydropic degeneration. Western blot analysis
      confirmed HSP27, HSP72 and HSP73 expression in normal and in pre-ulcerative
      mucosa of the pars oesophagea. Semi-quantitative analysis showed that for all
      three HSPs the immunoreactivity was more intense in pre-ulcerative mucosa than in
      normal mucosa. The different expression patterns observed may have functional
      significance; further studies are needed, however, to define the role of HSPs in
      swine oesophagogastric lesions, the aetiology and pathogenesis of which are
      largely unknown.

PMID- 15144796
TI  - Assessment of proliferative potentials of canine osteosarcomas and
      chondrosarcomas by MIB-1 immunohistochemistry and bromodeoxyuridine
      incorporation.
AB  - The proliferative potential of 17 canine osteosarcomas (OSs) (13 osteoblastic,
      two anaplastic, one fibroblastic and one chondroblastic), 18 chondrosarcomas
      (CSs) (13 mesenchymal and five ordinary), three osteomas, and one chondroma was
      evaluated immunohistochemically by labelling Ki-67 antigen with MIB-1 antibody,
      and incorporated bromodeoxyuridine (BrdU) with anti-BrdU antibody. The location
      of BrdU-positive cells in OSs and CSs was similar to that of MIB-1 positive
      cells, and the mean value of the BrdU labelling index (BrdU LI) and the MIB-1
      positive index (MIB-1 PI) in each case were significantly correlated (rs = 0.942,
      P < 0.05 with Spearman rank correlation coefficient; r = 0.779 P < 0.05 with
      linear regression analysis). The mean MIB-1 PI of OSs was 29.5%, which was
      approximately 2.5 times that of CSs, and the highest MIB-1 PI was 34.8% +/- 1.8
      S.E.M. in areas without osteoid. In CS cases, the survival rate after 24 months
      was significantly higher than in OS cases. The high MIB-1 PI therefore supports
      the view that OSs are clinically more aggressive than CSs in dogs. On the other
      hand, the highest MIB-1 PI values of mesenchymal CS components occurred in
      transitional areas, which were composed of poorly differentiated cells embedded
      in a myxomatous matrix between the chondroidal and mesenchymal regions. The MIB-1
      PI was 21.3% +/- 3.0 S.E.M. P < 0.001 in transitional areas. Proliferative
      markers may be useful in diagnosis and prognosis.

PMID- 15144797
TI  - Proliferation of protease-enriched mast cells in sarcoptic skin lesions of
      raccoon dogs.
AB  - Skin sites, tongue, lung, liver, jejunum and rectum from two raccoon dogs with
      Sarcoptes scabiei infestation and five normal (control) raccoon dogs were
      examined in terms of the distribution, proteoglycan properties and protease
      activity of mast cells. Infestation with S. scabiei caused a significant increase
      in the number of dermal mast cells. While the number of mast cells (average +/-
      standard deviation) in specimens of skin from the dorsum, dorsal neck, dorsal
      hind foot and dorsal fore foot was 40.0 +/- 19.8/mm2 in control animals, it was
      236.1 +/- 58.9/mm2 in the skin of mange-infested animals. Histochemical analysis
      revealed the glycosaminoglycan, heparin, within the mast cells of all organs
      examined in both control and affected animals. Enzyme-histochemical detection of
      serine proteases demonstrated an increase in mast-cell-specific protease activity
      (i.e., chymase and tryptase) in the skin of infested animals. The percentage of
      mast cells demonstrating chymase activity was 53.0 +/- 27.4% in control animals
      and 73.8 +/- 19.4% in mite-infested animals. The corresponding results for
      tryptase activity were 53.5 +/- 25.2% and 89.4 +/- 9.8%. Increases in mast cell
      chymase or tryptase activity, or both, were also observed within other organs of
      the infected animals, but the total number of mast cells found at such sites
      (with the exception of liver and ventrolateral pinna) did not differ from those
      of control animals.

PMID- 15144798
TI  - Tumour lines from a spontaneous rat endometrial stromal sarcoma, showing
      dendritic cell-like and myofibroblastic cell-like phenotypes.
AB  - A transplantable tumour (RY) and cell lines (RY-PB and clone RY-B-E3 isolated
      from RY-PB) were established from a naturally occurring endometrial stromal
      sarcoma (ESS) found in a 24-month-old female F344 rat. The primary tumour and RY
      tumours, which had been serially passaged in syngeneic female rats up to the 10th
      generation, consisted of spindle or round cells arranged in ill-defined bundles
      or sheets. Neoplastic cells of the primary and RY tumours, as well as cultured
      cells of RY-PB and RY-B-E3, showed positive reactions to vimentin, ED1/ED2 (both
      for rat macrophages/histiocytes), OX6 (for dendritic cells expressing rat MHC
      class II antigens), and lysosomal enzymes such as acid phosphatase and non
      specific esterase, in varying degrees. Ultrastructurally, neoplastic cells
      characteristically had tubulovesicular system-like structures and variously
      developed lysosomes in the cytoplasm. Neoplastic cells also exhibited
      immunoexpression to an alpha-smooth muscle actin (alpha-SMA). The addition of
      transforming growth factor (TGF)-beta1 to RY-PB and RY-B-E3 cultures increased
      the number of alpha-SMA-positive cells, whilst the positive cell number was
      decreased by anti-TGF-beta antibody. The RT-PCR method revealed the expression of
      TGF-beta1 mRNA in the cultured cells. The present study showed that rat ESS
      derived cells exhibited dendritic cell-like and myofibroblastic cell-like
      phenotypes. The histogenesis of ESSs in human beings and rats remains poorly
      understood, and these tumour lines may therefore become useful tools for further
      research.

PMID- 15144799
TI  - A narrow time-window for access to the brain by exogenous protein after
      immunological targeting of a blood-brain barrier antigen.
AB  - The endothelial barrier antigen (EBA) is a membrane protein expressed by
      endothelial cells of the rat blood-brain barrier (BBB). A previous short-term non
      recovery study demonstrated that immunological targeting of EBA by intravenous
      administration of a monoclonal antibody (anti-EBA) led to acute opening of the
      BBB to exogenous and endogenous tracers. The aims of the present study were to
      determine whether opening of the BBB was reversible and compatible with survival,
      and whether a "therapeutic window" existed. A single intravenous injection of one
      of three doses (high, medium and low) of anti-EBA was used. Animals were allowed
      to survive for periods ranging from 17 min to 4 days. The tracer horseradish
      peroxidase (HRP) was administered intravenously 10 min before perfusion fixation,
      and its distribution was assessed in Vibratome sections of the brain and spinal
      cord. Leakage of HRP into the central nervous system was dose- and time
      dependent. The medium dose produced incipient HRP leakage at 17 min and
      widespread pronounced leakage at 30 min. Progressive reduction in HRP
      permeability occurred from 45 min to 2 h, with barrier restoration by 3 h. At all
      subsequent time intervals (6 h-4 days) the BBB remained impermeable to HRP. The
      low and high doses produced less and greater HRP leakage, respectively, but
      restoration of the barrier still occurred at 3 h. The high dose, however,
      produced a number of deaths. Animals treated with an isotype control antibody
      showed no HRP leakage at comparable time intervals. The results indicated that
      (1) this model was compatible with survival, (2) opening of the BBB was
      monophasic and transient, occurring during a narrow "time-window", and (3) the
      barrier, once reconstituted, maintained its integrity.

PMID- 15144800
TI  - Mast cells and eosinophils in feline allergic dermatitis: a qualitative and
      quantitative analysis.
AB  - Mast cells (MCs) and eosinophils are prominent in the perivascular infiltrate of
      cats with allergic dermatitis. In the skin of allergic cats MCs were mainly
      observed diffusely in the superficial dermis, while eosinophils were found mainly
      in the deep dermis in a perivascular pattern. MC counts were significantly higher
      in cats with allergic dermatitis (P < 0.05) than in healthy control cats, but the
      number varied widely. Moreover, the numbers of eosinophils in the skin of
      allergic and control cats differed significantly (P < 0.05) none being found in
      the latter. There was no significant correlation between numbers of mast cells
      and eosinophils in the same biopsy sample. In the allergic cats, a significantly
      lower number of MCs was detected by staining for tryptase than by staining for
      chymase or by Astra blue staining. Additionally, the chymase: tryptase ratio in
      healthy cats was reversed in cats with allergic dermatitis. These changes were
      observed in lesional and nonlesional skin of cats with allergic dermatitis. The
      findings indicate a generalized effect on MCs in allergic dermatitis. In
      addition, eosinophils are an important indicator of allergic dermatitis.

PMID- 15144801
TI  - Expression of cyclooxygenase-1 and -2 in canine nasal carcinomas.
AB  - Cyclooxygenase-1 (COX-1) and cyclooxygenase -2 (COX-2) are known to play a role
      in the carcinogenesis of many human and animal primary epithelial tumours.
      However, expression of COX-1 and -2 has not been investigated in canine nasal
      epithelial carcinoma, a rare form of neoplasia. COX-1 immunolabelling was
      demonstrated in normal canine nasal mucosa and in a minority of neoplastic
      specimens. Cytoplasmic COX-2, however, was strongly expressed in the majority of
      canine nasal carcinomas. In addition, COX-2 expression was demonstrated in
      dysplastic epithelium and in a proportion of stromal cells. Co-expression of both
      enzyme isoforms was revealed by confocal laser scanning microscopy. The results
      indicate that COX-2 is overexpressed in a proportion of naturally occurring
      canine nasal carcinomas, suggesting its possible role in canine nasal
      tumorigenesis.

PMID- 15144802
TI  - Greater sensitivity of pigtailed macaques (Macaca nemestrina) than baboons to
      total body irradiation.
AB  - Two juvenile pigtailed macaques (animals 1 and 2) received total body irradiation
      (TBI) followed by autologous stem cell transplantation, by a procedure known to
      be well tolerated by baboons. In this procedure, the TBI consisted of treatment
      on two consecutive days with 255cGy on one side, followed after 1-2 min by a
      similar dose on the other side. The two pigtailed macaques showed rapid
      haematopoietic engraftment, but succumbed either to systemic cytomegalovirus
      (CMV) infection and necrotising colitis or to haemorrhagic cystitis and
      tubulointerstitial nephritis. For four further pigtailed macaques (animals 3-6)
      the radiation procedure was changed to four equal doses of 255cGy, given 6-12 h
      apart. Animals 4-6 all showed engraftment and survived for long periods (>218
      days), with no, or only minor treatable, complications. Animal 3 failed to show
      engraftment and succumbed to radiation-induced vascular lesions and severe
      multiorgan haemorrhages. The results suggest that pigtailed macaques have a lower
      tolerance threshold than baboons, rhesus macaques or human beings to TBI, the
      adverse effects of TBI being indistinguishable from those seen in human patients.
      The results also suggest that a hyperfractionated radiation procedure can prevent
      radiation-induced morbidity and mortality in pigtailed macaques.

PMID- 15144803
TI  - Epithelioid malignant peripheral nerve sheath tumour in a dog.
AB  - An unusual morphological variant of malignant peripheral nerve sheath tumour, in
      which the cells exhibited a predominantly epithelial morphology, was diagnosed in
      a dog. The animal had a history of progressive ataxia. Post-mortem examination
      revealed an infiltrative growth in the sublumbar region, encroaching on the L1
      and L2 vertebral bodies; additional masses were observed in the kidneys, liver
      and lungs. Histologically, the subcutaneous mass was composed of a dense
      population of spindle-shaped cells arranged in fascicles. The internal masses
      were composed of epithelioid cells arranged in a nodular pattern.
      Immunohistochemically, the spindle-shaped cells of the subcutaneous mass were
      positive for S-100, and the epithelioid cells of the internal growths exhibited
      weak S-100 immunoreactivity.

PMID- 15144804
TI  - Morphological changes in the parathyroid gland of rats with humoral
      hypercalcaemia of malignancy.
AB  - Morphological changes in parathyroid chief cells were investigated in rats with
      humoral hypercalcaemia of malignancy (HHM), induced by intraperitoneal
      inoculation with a rat pulmonary adenocarcinoma cell line, IP-B12. Inoculation
      with IP-B12 cells resulted in the production of parathyroid hormone-related
      protein (PTHrP); thus, IP-B12-bearing rats developed hypercalcaemia, with
      elevated plasma PTHrP concentrations and decreased serum PTH, at 5 to 7 weeks
      after the inoculation. Morphometrical analysis revealed an increase in the
      cytoplasmic area of chief cells in IP-B12-bearing rats, as compared with
      controls. Ultrastructurally, although the number of mature storage granules in
      the chief cells was similar in controls and IP-B12-bearing animals, degraded
      granules were significantly increased in tumour-bearing rats. In addition, the
      chief cells of IP-B12-bearing rats showed a trend towards decreased tortuosity of
      the cytoplasmic membrane, with simple interdigitations between adjacent cells.
      These findings suggested that under HHM conditions, PTH granules in the chief
      cells were maintained in the form of storage granules and were hydrolysed,
      resulting in the suppression of PTH release into the blood circulation. Serum PTH
      concentrations may be regulated by inhibition of secretion rather than
      suppression of granular synthesis in hypercalcaemic rats. This is the first
      description of morphological changes in the parathyroid gland of rats with HHM.

PMID- 15144805
TI  - A novel spongiform degeneration of the grey matter in the brain of a kitten.
AB  - A young female domestic short-hair cat presented with neurological signs
      consistent with a multifocal encephalic lesion (depressed mental status, head
      tilt to the right, cervical ventroflexion, head tremors, tetraparesis, conscious
      propioceptive deficits in all four limbs and visual deficits). No gross lesions
      were seen at necropsy. On light microscopical examination lesions were found only
      in the brain and cervical spinal cord. A generalized vacuolation of the grey
      matter of the brain was observed. Special staining techniques,
      immunohistochemistry, lectin affinity histochemistry and ultrastructural studies
      were performed to characterize the lesion; preservation of the white matter and a
      reactive astrogliosis were demonstrated. Feline retroviruses and PrPsc were not
      detected. Ultrastructurally, a dilatation of intracytoplasmic membrane-bounded
      organelles with membrane disruption and dendritic and somatic swelling was found
      in astrocytes and neurons. The age of the animal and histological changes
      suggested a novel, possibly congenital, spongiform degeneration of the brain and
      cervical spinal cord.

PMID- 15144806
TI  - Surfactant-templated nanomaterials synthesis.
AB  - The ability of amphiphilic compounds to self-assemble into well-defined
      structures can be taken advantage of for synthesis of inorganic materials with
      nanometer dimensions. The principle, which is biomimetic in character, is
      discussed with special attention put on three areas: microemulsion-based
      synthesis of nanoparticles, preparation of mesoporous materials from surfactant
      templates, and surfactant-mediated crystallization.

PMID- 15144807
TI  - Comparison of the structure and stability of monolayers prepared with 12
      phenyldodecyl mercaptan and 11-phenoxyundecyl mercaptan.
AB  - Monolayers are prepared by self-assembly of 12-phenyldodecyl mercaptan or 11
      phenoxyundecyl mercaptan on gold substrates. Reflection-absorption infrared
      spectra of these monolayers show that the 12-phenyldodecyl mercaptan monolayer
      forms a well-organized interface while 11-phenoxyundecyl mercaptan monolayers do
      not. Infrared spectra also suggest that the C1-C4 axis of the phenyl ring is
      largely parallel to the Au-substrate for 12-phenyldodecyl mercaptan layers, but
      has a more perpendicular orientation relative to the substrate for 11
      phenoxyundecyl mercaptan layers. Despite these structural differences, Zisman
      analysis of contact angle data shows that these monolayers have similar surface
      energies, 27.1 (+/-6.7) mN/m for 12-phenyldodecyl mercaptan and 26.1 (+/-5.3)
      mN/m for 11-phenoxyundecyl mercaptan. Fowkes analysis of the contact angle data
      suggest that dispersive interactions account for all of the measured surface
      energy for both modified interfaces. The structural differences are, however,
      reflected in the lateral stabilization energy measurements where monolayers of 12
      phenyldodecyl mercaptan are found to be 24 (+/-5) kJ/mol more stable than those
      of 11-phenoxyundecyl mercaptan.

PMID- 15144808
TI  - Adsorption of Congo red from aqueous solution onto calcium-rich fly ash.
AB  - The adsorption of Congo red from solution was carried out using calcium-rich fly
      ash with different contact times, concentrations, temperatures, and pHs. While
      the amount of dye adsorbed per unit weight of fly ash increases with increasing
      concentration and temperature, it decreases slightly with increasing pH. The
      adsorption was between 93 and 98% under the conditions studied. Kinetic studies
      showed that the adsorption process obeyed the pseudo-second-order kinetic model.
      It was also determined that the adsorption isotherm followed Freundlich and
      Dubinin-Radushkevich models. From thermodynamic studies, it was seen that the
      adsorption was spontaneous and endothermic. Desorption studies suggested that
      desorption was 29.18% in the presence of 0.1 N HCl and was 47.21% in the presence
      of CH(3)COOH (50% v/v). This indicated that most of the dye was held by fly ash
      via chemisorption as well as ion exchange. Furthermore, FTIR study also shows
      that a chemisorption process occurs between CR and fly ash, probably indicating
      dye/fly ash complexing.

PMID- 15144810
TI  - Micropatterning of lanthanum-based oxide thin film on self-assembled monolayers.
AB  - We studied the direct micropatterning of a lanthanum-based thin film on a
      template of self-assembled monolayers in an aqueous solution at 80 degrees C. The
      template composed of silanol and octadecyl areas was prepared by UV-modified
      octadecyltrichlorosilane SAMs through a photomask. The amorphous La(2)O(CO(3))(2)
      x H(2)O thin films were selectively deposited in the silanol regions.
      Crystallized La(2)O(3) was obtained after heating at 800 degrees C in air.

PMID- 15144809
TI  - Kinetic study on the sorption of dissolved natural organic matter onto different
      aquifer materials: the effects of hydrophobicity and functional groups.
AB  - The subsurface sorption of Suwannee River fulvic acid (SRFA) and humic acid
      (SRHA) onto a synthetic aquifer material (iron-oxide-coated quartz) and two
      natural aquifer materials (Ringold sediment and Bemidji soils) was studied in
      both batch and column experiments. The hypothesis that hydrophobic effects
      followed by ligand exchange are the dominant mechanism contributing to the
      chemical sorption happening between dissolved natural organic matter (NOM) and
      the mineral surfaces is supported by observations of several phenomena: nonlinear
      isotherms, faster sorption rates versus slower desorption rates, phosphate
      competition, a solution pH increase during NOM sorption, and functional groups
      and aromaticity-related sorption. In addition, high-pressure size exclusion
      chromatography (HPSEC) and carboxylic acidity showed that lower molecular weight
      NOM components of SRHA are preferentially sorbed to iron oxide, a result in
      contrast to that for SRFA. Phosphate increased the desorption of sorbed NOM as
      well as soil organic matter. All of these trends support ligand exchange as the
      dominant reaction between NOM and the iron oxide surfaces; however, if the soil
      surface has been occupied by soil organic matter, then the sorption of NOM is
      more due to hydrophobic effect.

PMID- 15144811
TI  - Kinetics and thermodynamics of the adsorption of some dyestuffs and p-nitrophenol
      by chitosan and MCM-chitosan from aqueous solution.
AB  - The effect of initial concentration, temperature, and shaking rate on the
      adsorption of three dyestuffs [orange II (O-II), crystal violet (CV), and
      reactive blue 5 (RB5)] and an ideal adsorbate, p-nitrophenol (PNP), by chitosan
      (Sigma C-3646) and the effect of temperature on the adsorption of O-II and CV by
      monocarboxymethylated chitosan (MCM-chitosan) were investigated. Kinetic data
      obtained for the adsorption of each dyestuff and PNP by chitosan and of O-II and
      CV by MCM-chitosan at different temperatures were applied to the Lagergren
      equation, and adsorption rate constants (k(ads)) at these temperatures were
      determined. These rate constants related to the adsorption of O-II and RB5 by
      chitosan and of O-II by MCM-chitosan were applied to the Arrhenius equation, and
      activation energies (E(a)) were determined. In addition, the isotherms for
      adsorption, at different temperatures, of each dyestuff and PNP by chitosan and
      of O-II and CV by MCM-chitosan were also determined. These isothermal data were
      applied to linear forms of isotherm equations that they fit, and isotherm
      constants were calculated. Because the isotherm curves obtained for the
      adsorption of O-II and CV by chitosan and of CV by MCM-chitosan fit the Langmuir
      adsorption isotherm, b constants were applied to thermodynamic equations, and
      thermodynamic parameters (delta G, delta H, and delta S) were calculated. Lastly,
      chitosan and MCM-chitosan were compared with respect to the ability to take up
      the dyestuffs and PNP.

PMID- 15144812
TI  - Physicochemical characterization of interfaces.
AB  - Reversed-flow inverse gas chromatography (RF-IGC) was used to measure, directly
      from experimental data, adsorption energies, local adsorption isotherms, the
      probability density function for the adsorption energies, and lateral interaction
      parameters, as distributed over experimental time. Local isotherms and the
      distribution energy function were correlated with adsorption energy. The results
      obtained are comparable to those calculated on the basis of the well-known
      integral equation. The RF-IGC method was used with the two most common
      hydrocarbons, acetylene and 1-butene, as probe gases, in the presence and absence
      of ozone, and with magnesium oxide and silicon oxide as solid adsorbents.

PMID- 15144814
TI  - Reaction of hydroquinone with hematite; I. Study of adsorption by electrochemical
      scanning tunneling microscopy and X-ray photoelectron spectroscopy.
AB  - The reaction of hematite with quinones and the quinone moieties of larger
      molecules may be an important factor in limiting the rate of reductive
      dissolution, especially by iron-reducing bacteria. Here, the electrochemical and
      physical properties of hydroquinone adsorbed on hematite surfaces at pH 2.5-3
      were investigated with cyclic voltammetry (CV), electrochemical-scanning
      tunneling microscopy (EC-STM), and X-ray photoelectron spectroscopy (XPS). An
      oxidation peak for hydroquinone was observed in the CV experiments, as well as
      (photo)reduction of iron and decomposition of the solvent. The EC-STM results
      indicate that hydroquinone sometimes forms an ordered monolayer with
      approximately 1.1 QH(2)/nm(2), but can be fairly disordered (especially when
      viewed at larger scales). XPS results indicate that hydroquinone and benzoquinone
      are retained at the interface in increasing amounts as the reaction proceeds, but
      reduced iron is not observed. These results suggest that quinones do not adsorb
      by an inner-sphere complex where adsorbate-surface interactions determine the
      adsorbate surface structure, but rather in an outer-sphere complex where
      interactions among the adsorbate molecules dominate.

PMID- 15144813
TI  - Interaction between poly(vinylimidazole) and sodium dodecyl sulfate: binding and
      adsorption properties at the silica/water interface.
AB  - The adsorption properties (adsorbed amount, kinetics, and reversibility) of
      poly(vinylimidazole) (PVI) and sodium dodecyl sulfate from PVI/SDS mixed
      solutions on negatively charged silica substrates were studied at pH 9 using
      reflectometry and compared to that measured on colloidal silica by the solution
      depletion method. In this paper, we will try to gain insight into the effect of
      PVI/SDS complex composition on the adsorption characteristics of the complex and
      particularly on the kinetics of the complex adsorption and its consequence on the
      adsorption reversibility. The properties of the complex in solution were
      characterized by means of potentiometric titration at a constant pH, binding
      isotherm, and surface tension measurements. On the basis of the experimental
      results the prevailing mechanism of the SDS/PVI interaction and the properties of
      the PVI/SDS complex were evaluated. Both the PVI/SDS complex uptake and the
      kinetics of the adsorption decreased with the amount of SDS bound to PVI. At low
      PVI/SDS binding ([SDS](0)<critical aggregation concentration CAC), the complex
      adsorption is transport limited while at high binding ([SDS](0)>CAC) the incoming
      complex experiences a blocking barrier of an electrostatic nature. This barrier
      has been confirmed by reversibility measurement, and the respective roles of the
      complex structure and charge were assessed.

PMID- 15144815
TI  - Reaction of hydroquinone with hematite; II. Calculated electron-transfer rates
      and comparison to the reductive dissolution rate.
AB  - The rate of reaction of hematite with quinones and the quinone moieties of larger
      molecules may be an important factor in limiting the rate of reductive
      dissolution of hematite, especially by iron-reducing bacteria. It is possible
      that the rate of reductive dissolution of hematite in the presence of excess
      hydroquinone at pH 2.5 may be limited by the electron-transfer rate. Here, a
      reductive dissolution rate was measured and compared to electron-transfer rates
      calculated using Marcus theory. An experimental rate constant was measured at 9.5
      x 10 (-6) s(-1) and the reaction order with respect to the hematite concentration
      was found to be 1.1. Both the dissolution rate and the reaction order of hematite
      concentration compare well with previous measurements. Of the Marcus theory
      calculations, the inner-sphere part of the reorganization energy and the
      electronic coupling matrix element for hydroquinone self-exchange electron
      transfer are calculated using ab initio methods. The second order self-exchange
      rate constant was calculated to be 1.3 x 10 (7) M(-1)s(-1), which compares well
      with experimental measurements. Using previously published data calculated for
      hexaquairon(III)/(II), the calculated electron-transfer rate for the cross
      reaction with hydroquinone also compares well to experimental measurements. A
      hypothetical reductive dissolution rate is calculated using the first-order
      electron-transfer rate constant and the concentration of total adsorbed quinone.
      Three different models of the hematite surface are used as well as multiple
      estimates for the reduction potential, the surface charge, and the adsorption
      density of hydroquinone. No calculated dissolution rate is less than five orders
      of magnitude faster than the experimentally measured one.

PMID- 15144816
TI  - Fe(3+) coordinated to amino-functionalized MCM-41: an adsorbent for the toxic
      oxyanions with high capacity, resistibility to inhibiting anions, and reusability
      after a simple treatment.
AB  - Fe(3+) coordinated to amino ligands fixed on MCM-41 mesoporous silica works as a
      strong adsorbent for toxic oxyanions. The maximum adsorption amounts were 1.56,
      0.99, 0.81, and 1.29 mmol g(-1) for arsenate, chromate, selenate, and molybdate,
      respectively. When the initial concentrations of oxyanions were less than 1 mmol
      l(-1), they were removed completely by adsorption and the distribution
      coefficients K(d) were found to be more than 200000. Inhibition of oxyanion
      adsorption by abundant competing anions found in nature, NO(3)(-), SO(4)(-),
      PO(4)(3)(-) and Cl(-), was evaluated at adsorption saturation. Among these
      anions, the adsorption of the oxyanions was inhibited most in the presence of
      PO(4)(3)(-) , with which the selectivities for the target oxyanions were still
      more than 80%. The other coexisting anions, NO(3)(-), SO(4)(-), PO(4)(3)(-) and
      Cl(-), had little influence on adsorption of the oxyanions except in the case of
      selenate removal from sulfate solution. The high ability and selectivity to the
      target oxyanions are attributed to specific interactions between Fe(3+) and the
      oxyanions. The acid treatment and re-coordination of Fe(3+) lead to a
      reactivation of the used adsorbent, in which 87-90% of the original adsorption
      capacity was obtained and the oxyanion/Fe stoichiometries were not changed.

PMID- 15144817
TI  - Supramolecular association of a triblock copolymer in water.
AB  - Solutions of a poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock
      copolymer, Pluronic F(68), were investigated in isothermal and isopleth mode.
      Surface tension, sigma, dynamic shear viscosity, n(omega), QELS experiments, and
      volumetric, colligative, and refractive index measurements characterize the
      system behavior in a wide range of compositions and temperatures. The
      thermodynamic properties associated with micelle formation, above the critical
      micellar temperature, were determined by different experimental methods. The
      large entropic contributions to the system stability are ascribed to significant
      dehydration of the oxypropylene portion in the copolymer, consequent to micelle
      formation. Temperature has a pronounced effect on the association features of
      F(68). It gives rise to abrupt changes in QELS and rheological properties when
      the critical micellar temperature is approached. Such effects are explained in
      terms of thermally driven micellization processes and interconnection between
      micelles.

PMID- 15144818
TI  - Dynamic motion of phosphorylcholine groups at the surface of poly(2
      methacryloyloxyethyl phosphorylcholine-random-2,2,2-trifluoroethyl methacrylate).
AB  - A series of novel random copolymers composed of hydrophilic and hydrophobic
      monomer units have been synthesized by a conventional radical polymerization
      method. As the hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine
      (MPC) was selected because the MPC polymers are well known for their excellent
      bio- and blood compatibilities. The semifluorinated monomer, 2,2,2-trifluoroethyl
      methacrylate (TFEMA), was used as the hydrophobic monomer. The surface analysis
      of the copolymer by X-ray photoelectron spectroscopy, dynamic contact angle
      measurement, and zeta-potential measurement showed that the TFEMA unit was
      concentrated at the outermost surface in the dry state. The dynamic reorientation
      of the MPC unit occurred in the wet state because the MPC unit had a strong
      hydrophilic character. As a result, the monomer unit composition on the surface
      became almost the same as that in the bulk. Nevertheless, the properties of the
      surface were hydrophilic in spite of the MPC unit composition of the bulk. In
      particular, the amount of protein adsorbed on the surface was dramatically
      reduced when the MPC unit mole fraction was 0.2.

PMID- 15144820
TI  - Adsorption of bilayers and multilayers of cationic and anionic co-polymers of
      acrylamide on silicon oxide.
AB  - Silica surfaces were consecutively treated with copolymers of cationic and
      anionic polyacrylamides (C-PAM and A-PAM, respectively) and the layer-by-layer
      build-up was continuously monitored with the aid of stagnation point adsorption
      reflectometry (SPAR). Four different charge densities of the cationic polymer and
      one charge density of the anionic polymer were studied. The solid substrate used
      in the investigation was an oxidized Si wafer, the charge of which was varied by
      performing the measurements at different pH. Adsorption measurements were
      performed both in deionized water and with a background electrolyte concentration
      of 0.01 M NaCl. The results show that the adsorption of C-PAM at pH 6 was
      dominated by electrostatic interactions. However, a significant nonionic
      contribution to the adsorption of C-PAM on SiO(2) was detected-when the results
      of adsorption measurements conducted in deionized water and in 0.01 M NaCl were
      compared. At pH 9, the adsorption of C-PAM onto SiO(2) was found to be
      geometrically restricted since the adsorption stoichiometry between the polymer
      charges and the charges on the surface was less than 1 irrespective of the charge
      of the C-PAM. Adsorption of the A-PAM onto the C-PAM covered surface increases as
      a function of the adsorbed charges in the first layer. Experiments showed that it
      was possible to form multilayers of polyelectrolytes on the SiO(2) surface
      provided the charge of the C-PAM was high enough. The critical charge of the
      polyelectrolyte for the formation of multilayers was also dependent on the charge
      of the substrate; that is, the lower the surface charge the higher the critical
      charge of the C-PAM. The substrate affected the amount of polyelectrolyte
      adsorbed up to the fifth layer. For further layers there was almost a
      stoichiometric relationship between the charges of the polyelectrolytes in
      consecutive layers. Results from studies of the formed multilayers with a quartz
      crystal microbalance (QCM-D) indicated that there was a close correlation between
      energy dissipation into the multilayers and a decrease in the adsorption as
      detected with SPAR. This in turn indicates that a decrease in the reflectometer
      signal does not necessarily indicate a decrease in adsorption.

PMID- 15144819
TI  - Architecture and solution properties of AB-type brush-block-brush amphiphilic
      copolymers via ATRP techniques.
AB  - Atom transfer radical polymerization (ATRP) was applied to the synthesis of AB
      type brush-block-brush amphiphilic copolymers. The procedure included the
      following steps: (1). ATRP of methacryloyl-terminated poly(ethylene glycol
      methylether) macromonomer (PEG-MC) gave well-defined PEG brush macroinitiator,
      (2). subsequent ATRP of 2-hydroxyethyl methacrylate (HEMA) with this brush
      macroinitiator provided PEG brush-block-PHEMA (brush-block-coil) diblock
      copolymers, (3). esterification of the pendant hydroxy groups of PHEMA block with
      2-bromoisobutyryl bromide yielded a block-type polyinitiator, brush-block-poly(2
      (2-bromoisobutyryloxy)ethyl methacrylate) (PBIEM), (4). ATRP of HEMA using brush
      block-PBIEM as polyinitiator provided AB-type brush-block-brush amphiphilic
      copolymers. Dilute-solution properties of such AB-type copolymer brushes were
      investigated by static and dynamic light scatterings. As a result, this copolymer
      exhibited a slightly ellipsoidal shape, i.e., Janus-type structure, in solution.

PMID- 15144821
TI  - On the origin of colloidal particles in the dispersion polymerization of aniline.
AB  - When aniline is oxidized in an aqueous medium in the presence of a steric
      stabilizer, colloidal polyaniline (PANI) dispersions are obtained. The generally
      accepted model of the stabilization assumes that the macromolecules of the water
      soluble steric stabilizer are adsorbed at the polymer, precipitating during the
      dispersion polymerization, and provide steric protection against further
      aggregation. An alternative mechanism of conducting-polymer particle formation is
      proposed in the present study. We suggest that the steric stabilizer provides a
      site for adsorption of oligoaniline initiation centers; subsequent polymerization
      from anchored centers yields particle nuclei that grow to produce colloidal PANI
      particles. This hypothesis is based on the observation that the colloidal
      particles are obtained only in the case where the steric stabilizer is introduced
      in the early stages of polymerization when aniline oligomers are present in the
      reaction mixture. If the stabilizer had been added during the growth of PANI
      chains, colloidal dispersions would not have been produced. The process of
      particle growth is completely analogous to the formation of conducting PANI films
      on the surface of microparticles and various materials. There, the polymerization
      of aniline at the surfaces is preferred to the same process proceeding in the
      bulk of the reaction mixture. While the films grow at the interfaces with the
      reaction mixture, the dispersion particles similarly emanate from the stabilizer
      chains. The particle size, the formation of nonspherical morphologies, the
      importance of the chemical nature of the stabilizer chains, and the general
      relation between the conducting-polymer film and particle growth are discussed in
      the light of the proposed model.

PMID- 15144823
TI  - Aggregate size distribution evolution for Brownian coagulation-sensitivity to an
      improved rate constant.
AB  - Brownian motion causes small aggregates to encounter one another and grow in
      gaseous environments, often under conditions in which the coalescence rate (say,
      spheroidization by "sintering") cannot compete. The polydisperse nature of the
      aerosol population formed by this mechanism is typically accounted for by
      formulating an evolution equation for the joint PDF of the state variables needed
      for describing individual particles. In the simple case of fractal-like
      aggregates (prescribed morphology and state, characterized just by the number of
      aggregated spherules, or total aggregate volume), we use the quadrature method of
      moments and Monte Carlo simulations to show that recent improvements in the laws
      governing free molecule regime coagulation frequency (rate "constant") of these
      aggregates cause systematic changes in the shape of the asymptotic aggregate size
      distribution, with significant implications for the light-scattering power and
      inertial impaction behavior of such aggregate populations.

PMID- 15144822
TI  - Competitive adsorption from mixed nonionic surfactant/protein solutions.
AB  - A thermodynamic model is derived which is suitable to describe adsorption from a
      mixed protein/surfactant solution. The comparison with experimental data for HSA
      mixed with the nonionic surfactant decyl dimethyl phosphine oxide shows good
      agreement. Some model calculations are discussed in terms of the competitive
      character of the process of adsorption from mixed protein/surfactant solutions.
      The behavior of globular (HSA) and flexible (beta-casein) proteins appears to be
      quite different due to the possibility of changing the molar area of adsorbed
      protein molecules.

PMID- 15144824
TI  - Shear-induced structure in polymer-clay nanocomposite solutions.
AB  - The equilibrium structure and shear response of model polymer-clay nanocomposite
      gels are measured using X-ray scattering, light scattering, optical microscopy,
      and rheometry. The suspensions form physical gels via the "bridging" of
      neighboring colloidal clay platelets by the polymer, with reversible adsorption
      of polymer segments onto the clay surface providing a short-range attractive
      force. As the flow disrupts this transient network, coupling between composition
      and stress leads to the formation of a macroscopic domain pattern, while the clay
      platelets orient with their surface normal parallel to the direction of
      vorticity. We discuss the shear-induced structure, steady-shear rheology, and
      oscillatory-shear response of these dynamic networks, and we offer a physical
      explanation for the mesoscale shear response. In contrast to flow-induced
      "banding" transitions, no stress plateau is observed in the region where
      macroscopic phase separation occurs. The observed platelet orientation is
      different from that reported for polymer-melt clay nanocomposites, which we
      attribute to effects associated with macroscopic phase separation under shear
      flow.

PMID- 15144825
TI  - Three-body collisions as a particle formation mechanism in silver nanoparticle
      synthesis.
AB  - Silver nanoparticles were prepared in a tubular flow reactor using an evaporation
      condensation technique. The size distribution of the particles was measured using
      standard aerosol instruments and electron microscopy. A comparison with results
      obtained by a discrete population balance model with molecule-by-molecule
      resolution suggest that the particles probably nucleate kinetically through a
      dimerization process instead of a thermodynamic pathway over a free energy
      barrier, as is typically described by classical nucleation theory. Furthermore,
      the kinetic rate of dimerization seems to be accompanied by a correction term,
      associated with the requirement of energy and momentum conservation in molecule
      molecule collisions. This energy conservation requires the presence of three-body
      collisions at the very initial step of particle formation.

PMID- 15144826
TI  - Electro-optic characteristics of optically interacting beta-FeOOH particles.
AB  - In this article the influence of multiple light scattering on the basic electro
      optic parameters of optically dense colloidal particles is analyzed. The model
      system is an aqueous suspension of monodisperse ellipsoidal beta-FeOOH particles
      that displays large electric light scattering variations, including sign
      reversal, at very low particle volume fractions (two orders of magnitude below
      the critical concentration of particle electric interactions). The scaling method
      permits the relative variations in particle electric polarizability to be
      followed and its relaxation frequency to be determined. Particle rotational
      relaxation frequency and the phase shift of the responses at this frequency are
      obtained by the alternating component of the effects. Characteristic field
      intensity curves in the low-frequency range are used to follow the relative
      changes induced by the slow electrokinetic effect. The experimental results show
      that, despite the drastic variations in the effects with volume fraction, the
      basic electro-optic parameters are independent of multiple scattering and can be
      adequately determined for any particle concentration, excluding a narrow range in
      the vicinity of the electro-optic sign reversal. The investigation demonstrates
      that the dependence of the frequency behavior of aqueous beta-FeOOH on particle
      volume fraction reported in the literature is due not to optical interactions but
      to variation of particle surface electric state in the process of dilution.

PMID- 15144827
TI  - Adsorption and conversion of various hydrocarbons on monolithic hydrocarbon
      adsorber.
AB  - Adsorption and conversion of various hydrocarbons on monolithic hydrocarbon
      adsorbers were studied using a new experimental model, temperature-programmed
      adsorption (TPA). In this study, methyl alcohol, acetone, acetaldehyde, 2,2,4
      trimethylpentane, n-octane, and toluene were chosen as model hydrocarbons for
      cold start of a vehicle. The effect of the hydrocarbon components and oxygen
      concentration on the TPA curve was investigated. Depending on the presence of
      O(2), the adsorbed and desorbed amounts of the hydrocarbons were decreased, while
      the conversion efficiency of the hydrocarbons was increased. In the case of
      hydrocarbons containing oxygen, the thermal decomposition appeared to be in the
      order methanol, acetaldehyde, and acetone.

PMID- 15144828
TI  - Determination of fiber charge components of Lo-solids unbleached kraft pulps.
AB  - Four different titration methods for measurement of fiber charge were used in
      this study. Each method gave different fiber charge values depending on the
      acidity of the end point and the interaction between the fiber chemical
      components and the titrant. Also, the interactions between the ionizable groups
      on the fiber had significant effects on the interpretation of these results. The
      conductometric titrations showed trends similar to the results obtained from the
      potentiometric titration. The conductometric titrations with NaOH produced higher
      fiber charge values, higher than the titrations with NaHCO(3). The differences
      between the results obtained from the potentiometric and polyelectrolyte
      titrations, which were associated with the dissolved fiber components during the
      delignification, were linearly related to the Kappa number of pulps. The positive
      intercept of this linear relationship indicated that the kraft pulping process
      not only removed the ionizable groups associated with the dissolved components,
      but at the same time provided conditions to form new ionizable groups in the
      fibers. The polyelectrolyte titration results indicated that the lignin content
      in the fibers did not affect the fiber surface charge. Data extracted from the
      FTIR spectra of protonated fibers were highly correlated with the fiber charge
      values obtained from the conductometric titration with NaOH.

PMID- 15144829
TI  - Effect of dialysis treatment on the aggregation state of montmorillonite clay.
AB  - In this work dialysis was used as a technique to modify the aggregation state of
      montmorillonite clay. Na-montmorillonite clay suspension was treated by a
      dialysis process and the effect of dialysis time on the surface area of the
      treated clay was studied. In a clay suspension, a decrease in cation content
      increases the interparticle repulsion forces exponentially, leading to separation
      of clay into the elementary clusters of layers by osmotic swelling. During
      dialysis treatment, the classical delamination process and mechanism were not
      observed. According to N(2) adsorption isotherms, the increase of surface area
      concerns to the development of mesoporosity. Nevertheless, the surface area
      increase cannot be explained by the delamination or exfoliation of some layers,
      since an increase in the expected number of layers that would yield the surface
      area does not explain the mesoporosity observed after dialysis. Based on these
      results, a new mechanism of evolution of the clay aggregation state after
      dialysis and drying is proposed.

PMID- 15144830
TI  - Comparative study of carbon dioxide and nitrogen atmospheric effects on the
      chemical structure changes during pyrolysis of phenol-formaldehyde spheres.
AB  - The effect of CO(2) atmosphere on the chemical structure changes of resol-type
      phenol-formaldehyde spheres during pyrolysis was investigated, in comparison with
      that of N(2) atmosphere, using FT-IR, TGA, and elemental analysis techniques. It
      was found that, in contrast to the expectation that CO(2) may act as an oxidizing
      agent at high temperature, it behaves very similar to N(2) during pyrolysis of PF
      spheres up to 700 degree C, but results in a somewhat different extent of some
      specific reactions. That is, although the reactions occurring up to 700 degree C
      were dominated by crosslinking and/or polyaromatization under both CO(2) and N(2)
      atmospheres, fewer alkyl-phenolic ether bonds were formed under CO(2) than under
      N(2). As a consequence, the samples carbonized under CO(2) at 700 degree C were
      found to have more pendant groups on the edge carbon atoms of carbon in the
      carbonized samples than those prepared under N(2) atmosphere.

PMID- 15144831
TI  - Corrected Debye-Huckel analysis of surface complexation; III. Spherical particle
      charging including ion condensation.
AB  - Statistical mechanics has been used to derive a model for the charging of a
      spherical particle in a salt solution to complement our experimental studies and
      gain a deeper understanding of the processes involved in surface complexation.
      Our chosen model goes beyond the equilibrium constants and the Gouy-Chapmann
      theory currently used in surface complexation models. The proton adsorption is
      taken to occur at a harmonic potential well on the surface characterized by a
      frequency v and a well depth u(0). Outside the particle surface there is a
      capacitor layer of width w(c) which is impenetrable to the salt ions. The diffuse
      screening of the charged particle is described by a corrected Debye-Huckel
      analysis accounting for ion size in the ion-ion interactions. To account also for
      nonlinear electrostatic response a layer of condensed counterions has been
      introduced. The criterion for the onset of ion condensation is that the
      electrostatic field exceeds a linear response criterion. Ion size effects are
      accounted for in terms of hole-corrected electrostatic energies and excluded
      volume. The model has been applied to titrated surface charge data on goethite
      (alpha-FeOOH) at various background concentrations and good agreement between the
      experimental data and the model was obtained. Both the size of the screening ions
      and the central particle size were shown to be of importance for the surface
      charge.

PMID- 15144832
TI  - Copper (II) adsorbed on SiO(2)/SnO(2) obtained by the sol-gel processing method:
      application as electrochemical sensor for ascorbic acid.
AB  - With the objective of producing a material showing better conductive properties
      to be used as a support for electroactive species, a SiO(2)/SnO(2) mixed oxide
      was prepared. The procedure for SiO(2)/SnO(2) mixed oxide preparation using the
      sol-gel processing method, starting from tetraethylorthosilicate and SnI(4) as
      precursor reagents, is described. SiO(2)/SnO(2) with composition Sn=15.6 wt% and
      S(BET) = 525 m(2)g(-1), V(p)=0.28 mlg(-1), and D(p)= 1.5 nm, where S(BET), V(p)
      and D(p) are the specific surface area, the average pore volume, and the average
      pore diameter, respectively, was obtained. The X-ray photoelectron spectroscopy
      showed that the mixed oxide was thermally very stable for samples heat-treated at
      up to 1073 K. The Bronsted acid sites, probed with pyridine molecules for samples
      heat-treated at various temperatures, were chemically stable up to 473 K.
      Segregation of SnO(2) crystalline phase was observed at 1473 K but no crystalline
      phase was verified for SiO(2) at this temperature. The porous SiO(2)/SnO(2)
      matrix was used as base for Cu(II) immobilization and an electrode was developed
      for application in electrochemical detection of vitamin C in tablets.

PMID- 15144833
TI  - Effect of chlorine on adsorption/ultrafiltration treatment for removing natural
      organic matter in drinking water.
AB  - In drinking water treatment, prechlorination is often applied in order to control
      microorganisms and taste-and-odor-causing materials, which may influence organics
      removal by adsorption and membrane filtration. Thus, the addition of chlorine
      into an advanced water treatment process using a hybrid of adsorption and
      ultrafiltration (UF) was investigated in terms of natural organic matter (NOM)
      removal and membrane permeability. A comparison between two adsorbents, iron
      oxide particles (IOP) and powdered activated carbon (PAC), was made to understand
      the sorption behavior for NOM with and without chlorination. Chlorine modified
      the properties of dissolved and colloidal NOM in raw water, which brought about
      lower TOC removal, during IOP/UF. The location of IOPs, whether they were in
      suspension or in a cake layer, affected NOM removal, depending on the presence of
      colloidal particles in feedwater. Chlorine also played a role in reducing the
      size of particulate matter in raw water, which could be in close association with
      a decline in permeate flux after chlorination.

PMID- 15144834
TI  - Effect of activation temperature on the textural and chemical properties of
      potassium hydroxide activated carbon prepared from pistachio-nut shell.
AB  - The effect of activation temperature on the textural and chemical properties of
      activated carbons prepared from pistachio-nut shells by potassium hydroxide
      activation was studied. Relatively high activation temperature was required to
      develop high porosities. However, too high an activation temperature resulted in
      the burn-off of the carbon structures and the widening of micropores to meso- and
      macropores. The microstructures and microcrystallinities of the carbons prepared
      were examined using a scanning electron microscope and a powder X-ray diffraction
      analyzer, respectively, while the Fourier transform infrared spectra indicated
      the changes in the surface functional groups that were formed during the
      different preparation stages.

PMID- 15144835
TI  - Synthesis and characterization of ultrathin multilayer films based on molybdenum
      polyoxometalate (Mo(54)).
AB  - The crown-shaped molybdenum polyoxometalate cluster
      Na(26)[[Na(H(2)O)(2)](6)[(micro(3) -OH)(4) (Mo(20)(V)), (Mo(34)(VI)(O)(164)
      (micro-CH(3)COO(4)) x 120H(2)O(Mo(54)) was synthesized and first used as a bulk
      modifier to fabricate a three-dimensional modified WIGE electrode by the layer-by
      layer method. The (Mo(54))/PAH)(n) multilayer films have been characterized by X
      ray photoelectron spectra (XPS) and atomic force microscopy (AFM). UV-vis
      measurements reveal regular film growth with each Mo(54) adsorption. The
      electrochemical method was used to characterize the modified WIGE electrode,
      which is important for practical applications.

PMID- 15144836
TI  - Angstrom-to-millimeter characterization of sedimentary rock microstructure.
AB  - Backscatter SEM imaging and small-angle neutron scattering (SANS) data are
      combined within a statistical framework to quantify the microstructure of a
      porous solid in terms of a continuous pore-size distribution spanning over five
      orders of magnitude of length scale, from 10 A to 500 microm. The method is
      demonstrated on a sample of natural sandstone and the results are tested against
      mercury porosimetry (MP) and nuclear magnetic resonance (NMR) relaxation data.
      The rock microstructure is fractal (D=2.47) in the pore-size range 10 A-50 microm
      and Euclidean for larger length scales. The pore-size distribution is consistent
      with that determined by MP. The NMR data show a bimodal distribution of proton
      T(2) relaxation times, which is interpreted quantitatively using a model of
      relaxation in fractal pores. Pore-length scales derived from the NMR data are
      consistent with the geometrical parameters derived from both the SEM/SANS and MP
      data. The combined SANS/BSEM method furnishes new microstructural information
      that should facilitate the study of capillary phenomena in hydrocarbon reservoir
      rocks and other porous solids exhibiting broad pore-size distributions.

PMID- 15144837
TI  - Dodecyl sulfate-hydrotalcite nanocomposites for trapping chlorinated organic
      pollutants in water.
AB  - A series of hybrid organic-inorganic nanocomposite materials was synthesized by
      three different procedures using sodium dodecyl sulfate (DDS) and magnesium
      aluminum layered double hydroxide (Mg/Al LDH with a Mg/Al molar ratio of 2 to 5).
      Both the pH of the exchange medium (6.5 to 10) and the Mg/Al molar ratio of the
      LDH affected the basal spacing, the content of DDS retained and the orientation
      of the DDS chains within the interlamellar space. For LDH with higher charge
      density (Mg/Al=2 and 3), DDS molecules likely formed a perpendicular monolayer
      within the LDH interlayer and the solution pH had little effect on the basal
      spacing, with a mean and standard deviation of 25.5+/-0.4 A. However, for LDH
      with lower charge density (Mg/Al=4 and 5), DDS molecules more likely formed an
      interpenetrating bilayer, and the basal spacing significantly increased with
      increasing pH, with a mean and standard deviation of 32.7+/-5.2 A. Sorption of
      trichloroethylene and tetrachloroethylene by DDS-LDH varied with synthesis
      conditions, LDH type and DDS configuration in the interlayer. DDS-Mg(3)Al-LDH had
      the highest affinity for both trichloroethylene and tetrachloroethylene in water,
      either comparable to or as much as four times higher than other clay-derived
      sorbents, followed by DDS-Mg(4)Al-LDH and DDS-Mg(5)Al-LDH. DDS-Mg(2)Al-LDH had
      the lowest sorption affinity although the highest amount of DDS. The pH of the
      exchange solution also affected the amount of DDS retained by the LDH as well as
      the sorption efficiency. Mg(3)Al-LDH has a charge equivalent area of 32.2
      A(2)/charge, which allows the formation of optimal DDS configuration within its
      interlayer, thus resulting in the highest affinity for the chlorinated compounds.
      The DDS-Mg/Al-LDHs can be easily synthesized either ex situ or in situ at low
      temperature, indicating the feasibility of practical applications. The results
      obtained by controlling the synthesis procedure suggest that different
      arrangements of DDS molecules in the LDH interlayers can be obtained and
      optimized for the sorption of specific sorbates.

PMID- 15144838
TI  - Effect of charged colloidal particles on adsorption of surfactants at oil-water
      interface.
AB  - A change of oil/water interfacial tension in the presence of cationic or anionic
      surfactants in an organic phase was observed due to the addition of charged fine
      solids in the aqueous phase. The charged fine solids in the aqueous phase adsorb
      surfactants diffused from the oil phase, thereby causing an increase in the bulk
      equilibrium surfactant concentration in the aqueous phase, governed by the Stern
      Grahame equation. Consequently, surfactant adsorption at the oil-water interface
      increases, which was demonstrated from the measured reduction of the oil-water
      interfacial tension. The increased surfactant partition in the aqueous phase in
      the presence of the charged particles was confirmed by the measured decrease in
      the surface tension for the collected aqueous solution after solids removal, as
      compared with the cases without solids addition.

PMID- 15144839
TI  - Experimental determination of interfacial tension by different dynamical methods
      under simple shear flow conditions with a novel computer-controlled parallel band
      apparatus.
AB  - We present experimental investigations on droplet deformation under simple shear
      flow conditions, using a computer-controlled parallel band apparatus and an
      optical device which allows us to record the time dependence of the droplet
      shape. Several methods are applied to determine the interfacial tension from the
      observed shape and relaxation mechanism. Specific software developed in our
      laboratory allows the droplet to be fixed in a certain position for extended
      times, in fact, indefinite. This is an advantage over most other work done in
      this area, where only limited time is available. In our experiments, the
      transient deformation of sheared droplets can be observed to reach the steady
      state. The measured systems were Newtonian, both droplet and fluid phase. Droplet
      deformation, orientation angle and retraction were studied and compared to
      several models. The interfacial tension of the different systems was calculated
      using the theories of Taylor, Rallison, and Hinch and Acrivos. The results
      obtained from the analysis of the droplet deformation were in very good agreement
      with drop detachment experiments of Feigl and co-workers. The study of
      orientation angle shows qualitative agreement to the theory of Hinch and Acrivos
      but reveals larger quantitative discrepancies for several empirical fitting
      parameters of the used model. Analysis of the relaxation of sheared drops
      provided estimates of the interfacial tension that were in very good agreement
      with the steady-state measurements.

PMID- 15144840
TI  - Contact angle measurement on rough surfaces.
AB  - A new method for the measurement of apparent contact angles at the global energy
      minimum on real surfaces has been developed. The method consists of vibrating the
      surface, taking top-view pictures of the drop, monitoring the drop roundness, and
      calculating the contact angle from the drop diameter and weight. The use of the
      new method has been demonstrated for various rough surfaces, all having the same
      surface chemistry. In order to establish the optimal vibration conditions, the
      proper ranges for the system parameters (i.e., drop volume, vibration time,
      frequency of vibration, and amplitude of vibration) were determined. The
      reliability of the method has been demonstrated by the fact that the ideal
      contact angles of all surfaces, as calculated from the Wenzel equation using the
      measured apparent contact angles, came out to be practically identical. This
      ideal contact angle has been compared with three methods of calculation from
      values of advancing and receding contact angles.

PMID- 15144842
TI  - Self-assembly in linker-modified microemulsions.
AB  - Linker molecules are added to microemulsion systems to enhance the interaction
      between the surfactant and oil (lipophilic linkers) or water (hydrophilic
      linkers) phases. Previous results suggest that when lipophilic and hydrophilic
      linkers are combined they behave as a self-assembled surfactant at the oil/water
      interface. In this work we investigate this self-assembly phenomenon as a
      function of surfactant, linker and electrolyte concentration. We find that middle
      phase microemulsion appears at a specific concentration higher than the critical
      micelle concentration (CMC), which we denote as the critical middle phase
      microemulsion concentration (CmicroC). When the lipophilic linker dodecanol is
      added in equimolar ratio to the hydrophilic linker sodium mono- and dimethyl
      naphthalene sulfonate (SMDNS), the middle phase microemulsion did not appear
      until the surfactant sodium dihexyl sulfosuccinate (SDHS) concentration was
      larger than the CmicroC of the SDHS-alone system. Dodecanol is shown to segregate
      near the surfactant tails following a Langmuir-type adsorption process. This
      segregation is not affected by the electrolyte concentration but is significantly
      reduced when the surfactant (SDHS) concentration approaches the CmicroC. The data
      suggest that the self-assembly between hydrophilic and lipophilic linkers to form
      middle phase microemulsions is only possible if a minimum amount of surfactant is
      present.

PMID- 15144843
TI  - Computer simulation studies of surfactant monolayer mixtures at the water/oil
      interface: charge distribution effects.
AB  - Charge distribution effects on polar head groups for a mixture of amphiphilic
      molecules at the water/oil interface were studied. For this purpose a model which
      allowed us to investigate the charge effects exclusively was created. As a
      molecular model we used the structure of sodium dodecyl sulfate. Then we prepared
      molecules with the same molecular structure but with different charge
      distributions in order to have one cationic and one nonionic molecule. So, in
      this way, we were able to focus only in the charge effects. The monolayer
      mixtures were composed of anionic/nonionic and cationic/nonionic surfactants.
      Simulations of these systems show that the location of the different surfactants
      at the interface is determined by the interaction and the charge distribution of
      the molecules. Due to the difference in the charge distribution of the surfactant
      monolayers, the water molecules present distinct orientations in the mixture.
      Finally, it was found that the electrostatic potential difference across the
      interface depended on the interactions (charge distribution) of the anionic,
      cationic, and nonionic molecules in the mixture.

PMID- 15144841
TI  - Spectroscopic study on binding behaviors of different structural nonionic
      surfactants to cyclodextrins.
AB  - The binding of polyethylene glycol (10) n-octylphenyl ether (OPE) and
      polyethylene glycol (10) tert-octylphenyl ether (Triton X-100, TX) to beta
      cyclodextrin (beta-CD) and heptakis(2,3- beta-dimethyl)- beta-CD (DM- beta-CD)
      was described in detail by surface tension, steady-state fluorescence of OPE and
      TX, and phosphorescence of 1-bromonaphthalene (BN) probe. Surface tension and
      fluorescence measurements show that beta-CD entraps the hydrophobic moieties of
      OPE and TX to form inclusion complexes with the stoichiometry of 1:1. Unlike the
      n-octyl group of OPE, however, the tert-octyl group of TX fails to be
      encapsulated into the cavity of DM- beta-CD because of the steric hindrance of
      methyl groups at the rim of the cavity. The inclusion of the phenyl group of OPE
      and TX was demonstrated by dynamic quenching effect of iodide ion on fluorescence
      of OPE and TX in the presence of beta-CD. Static fluorescence quenching of OPE
      and TX by BN, phosphorescence of BN, and energy transfer between TX and BN
      provide additional evidence for the inclusion of their phenyl groups into the CD
      cavity. Analyses of molecular size suggest that the longer tert-octyl group of
      OPE is situated in curled manner in the cavity and the tert-octyl group of TX
      undergo a slight distortion for fit of beta-CD. Further introduction of the third
      guest component into the CD cavity occupied by OPE and TX will force the flexible
      octyl groups of OPE and TX to deform to a greater extent.

PMID- 15144844
TI  - Stability and rheology of emulsions containing sodium caseinate: combined effects
      of ionic calcium and alcohol.
AB  - We have investigated the combined effect of ionic calcium and ethanol on the
      visual creaming behavior and rheology of sodium caseinate-stabilized emulsions (4
      wt% protein, 30 vol% oil, pH 6.8, mean droplet diameter 0.4 microm). A range of
      ionic calcium concentrations, expressed as a calcium/caseinate molar ratio R, was
      adjusted prior to homogenization and varying concentrations of ethanol were added
      shortly after homogenization. A stability map was produced on the basis of visual
      creaming behavior over a minimum period of 8 h for different
      calcium/caseinate/ethanol emulsion compositions. A single narrow stable
      (noncreaming) region was identified, indicating limited cooperation between
      calcium ions and ethanol. The shear-thinning behavior of the caseinate-stabilized
      emulsions is typical of systems undergoing depletion flocculation. Addition of
      calcium ions and/or ethanol was found to lead to a pronounced reduction in
      viscosity and the onset of Newtonian flow. The state of aggregation was
      correlated with emulsion microstructure from confocal laser scanning microscopy.
      Time-dependent rheology (18 h) with a density-matched oil phase (1
      bromohexadecane) revealed that the visually stable emulsions were time
      independent low-viscosity fluids. Surface coverage data showed that increasing
      amounts of caseinate were associated with the oil-water interface with increasing
      R and ethanol content. A decrease in free calcium ions in the aqueous phase with
      moderate increases in R and ethanol content was observed, which is consistent
      with greater calcium-caseinate binding (aggregation). Ostwald ripening occurred
      at the high-ethanol emulsion compositions that were stable to depletion
      flocculation. While the coarsening rate was low, this can account for the cream
      plug formation observed during gravity creaming experiments. The caseinate
      emulsion with no ionic calcium or ethanol exhibits depletion flocculation from
      excess nonadsorbed caseinate submicelles. Addition of calcium ions reduces the
      submicelle number density via specific calcium-binding in the aqueous phase
      (fewer, larger calcium-caseinate aggregates) and at the droplet surface
      (increased surface coverage). Nonspecific ethanol-induced (calcium-dependent)
      caseinate submicelle aggregation in the bulk phase and on the droplet surface
      (increased surface coverage) culminates in a reduction in the number density of
      caseinate submicelles. A narrow window of inhibition of depletion flocculation
      occurs in systems containing both calcium ions and ethanol, both species
      combining to aggregate the protein and so reduce the density of free submicelles.

PMID- 15144845
TI  - The electroviscous force between charged particles: beyond the thin-double-layer
      approximation.
AB  - We have investigated the hydrodynamic drag force between charged particles in
      electrolyte solutions, specifically the electroviscous force that arises from the
      distortion of the electrical double layers by the flow field. We report an
      improvement on the thin-double-layer theory (S.G. Bike, D.C. Prieve, J. Colloid
      Interface Sci. 136 (1990) 95-112), using a more accurate boundary condition for
      the radial charge current. The differences become important when the double
      layers start to overlap. We have found that nonlinear hydrodynamic effects are
      small, whereas nonlinear electric effects can be significant, in some instances
      leading to qualitatively different behavior. If the ion diffusivities are highly
      asymmetric, the electroviscous force can be reduced by an order of magnitude when
      there is an excess of the mobile ions in the double layer. The common supposition
      that there are substantial differences in the electroviscous force predicted by
      constant-charge and constant-potential boundary conditions is incorrect; our
      calculations show that it is an artifact introduced by the Debye-Huckel
      approximation.

PMID- 15144846
TI  - Investigation of dynamic streaming potential by dimensional analysis.
AB  - The theory of streaming potential at sinusoidal flow of liquid in a porous medium
      is a convenient and fruitful tool for determination of the interface properties
      of materials and also for construction of apparatus for zeta potential
      measurements and electrokinetic transducers. An investigation of the dynamic
      streaming potential by the method of dimensional analysis is presented. This
      method provides a wider approach to the problem under consideration. As a result,
      relationships between streaming potential in a porous medium and mechanical
      quantities are established. These quantities include pressure gradient in a
      liquid inside pores and capillaries, acceleration of capillaries, and the solid
      part of a porous medium, and the viscous friction force the liquid exerts on the
      solid part. The corresponding formulas for streaming potential are presented. The
      relationship between the streaming potential and viscous friction force does not
      depend on the frequency of oscillation and pore size. All these formulas in
      particular cases are transformed to known formulas for the streaming potential.

PMID- 15144847
TI  - Decarboxylation of 6-nitrobenzisoxazole-3-carboxylate as kinetic probe for
      piperazinium-based cationic micelles.
AB  - A new class of cationic surfactants containing the heterocyclic piperazinium ring
      in their covalent structure was prepared; cetyldialkylpiperazinium halides, CRPX,
      with alkyl=Me (CMPX), Et (CEPX), n-Pr (CPPX), and with halide=Br and Cl. They
      were characterized by measures of critical micellar concentration, cmc, and
      ionization degree, alpha, and also by use of the decarboxylation of 6
      nitrobenzisoxazole-3-carboxylate as a kinetic probe to investigate the properties
      of the microinterface they provide in aqueous solutions. The pseudophase kinetic
      treatment fails to fit the data at high [surfactant], which show anomalies with
      abrupt increase in k(obs), especially for CEPX and CPPX. Data can be fitted up to
      [surfactant] ca. 0.1 M, and 0.2 M in some cases. Compared with
      cetyltrialkylammonium halides, values of k'(M) indicate a water-richer
      microenvironment and less important interface property changes with increasing
      head group bulk. The reaction could be studied both in the presence and in the
      absence of NaOH; comparison shows that NaOH affects only the shape of the kinetic
      profile at low [surfactant], without affecting the microenvironment provided by
      mature micelles.

PMID- 15144848
TI  - Genotype-phenotype correlations in FTDP-17: does form follow function?

PMID- 15144849
TI  - Following the leader: fibrillization of alpha-synuclein and tau.

PMID- 15144850
TI  - Intracranial electrophysiological investigation of the human brain in patients
      with epilepsy: contributions to basic and clinical research.

PMID- 15144851
TI  - New roles for VEGF in nervous tissue--beyond blood vessels.
AB  - Vascular endothelial growth factor (VEGF) is a secreted dimeric polypeptide that
      until recently has been believed to be a specific mitogen for endothelial cells
      subserving angiogenesis and permeability in development and after injury. Recent
      studies have depicted the localization of VEGF and its receptors on neurons and
      astrocytes and it has been shown to induce neuritic growth and to provide
      neuroprotection particularly after ischemia or spinal cord injuries. VEGF also
      shares common receptor signaling with the guidance molecule SEMA3A and thus could
      have an additional role linking the coordinated patterning of developing vascular
      and nervous tissue. It is now apparent that VEGF's role in nervous tissue is
      pleiotropic in nature, and further elucidation of its mechanisms of action may
      serve as a key substrate in understanding aspects of neural repair and
      development.

PMID- 15144852
TI  - Remyelination, axonal sparing, and locomotor recovery following transplantation
      of glial-committed progenitor cells into the MHV model of multiple sclerosis.
AB  - The behavior and myelinogenic properties of glial cells have been well documented
      following transplantation into regions of focal experimental demyelination in
      animal models. However, the ability of glial cell preparations to remyelinate in
      such models does not necessarily indicate that their transplantation into
      demyelinated lesions in clinical disease will be successful. One of the
      precluding factors in this regard is a greater understanding of the environmental
      conditions that will support transplant-mediated remyelination. In this study, we
      determined whether the complex and reactive CNS environment of the mouse
      hepatitis virus (MHV) model of multiple sclerosis (MS) could support transplant
      mediated remyelination. Striatal neural precursors derived from postnatal day 1
      mice were committed to a glial cell lineage and labeled. Immunohistochemical
      staining indicated that this population generated >93% glial cells following
      differentiation in vitro. Transplantation of glial-committed progenitor cells
      into the T8 spinal cord of MHV-infected mice demonstrating complete hindlimb
      paralysis resulted in migration of cells up to 12 mm from the implantation site
      and remyelination of up to 67% of axons. Transplanted-remyelinated animals
      contained approximately 2x the number of axons within sampled regions of the
      ventral and lateral columns as compared to non-transplanted animals, suggesting
      that remyelination is associated with axonal sparing. Furthermore,
      transplantation resulted in behavioral improvement. This study demonstrates for
      the first time that transplant-mediated remyelination is possible in the
      pathogenic environment of the MHV demyelination model and that it is associated
      with locomotor improvement.

PMID- 15144853
TI  - Bone marrow stromal cells infused into the cerebrospinal fluid promote functional
      recovery of the injured rat spinal cord with reduced cavity formation.
AB  - The effects of bone marrow stromal cells (BMSCs) on the repair of injured spinal
      cord and on the behavioral improvement were studied in the rat. The spinal cord
      was injured by contusion using a weight-drop at the level of T8-9, and the BMSCs
      from the bone marrow of the same strain were infused into the cerebrospinal fluid
      (CSF) through the 4th ventricle. BMSCs were conveyed through the CSF to the
      spinal cord, where most BMSCs attached to the spinal surface although a few
      invaded the lesion. The BBB score was higher, and the cavity volume was smaller
      in the rats with transplantation than in the control rats. Transplanted cells
      gradually decreased in number and disappeared from the spinal cord 3 weeks after
      injection. The medium supplemented by CSF (250 microl in 3 ml medium) harvested
      from the rats in which BMSCs had been injected 2 days previously promoted the
      neurosphere cells to adhere to the culture dish and to spread into the periphery.
      These results suggest that BMSCs can exert effects by producing some trophic
      factors into the CSF or by contacting with host spinal tissues on the reduction
      of cavities and on the improvement of behavioral function in the rat. Considering
      that BMSCs can be used for autologous transplantation, and that the CSF infusion
      of transplants imposes a minimal burden on patients, the results of the present
      study are important and promising for the clinical use of BMSCs in spinal cord
      injury treatment.

PMID- 15144854
TI  - Fibrillization of alpha-synuclein and tau in familial Parkinson's disease caused
      by the A53T alpha-synuclein mutation.
AB  - Mutations in the alpha-synuclein (alpha-syn) gene are responsible for a rare
      familial parkinsonism syndrome, a finding that has led to extensive
      characterization of altered alpha-syn structure in sporadic Parkinson's disease
      (PD) and other neurodegenerative disorders. We report here the
      immunohistochemical, biochemical and ultrastructural characterization of alpha
      syn neuropathology in a case of familial PD with the A53T alpha-syn gene
      mutation. Insoluble filamentous alpha-syn lesions were detected in almost all
      brain regions examined and as in sporadic PD, we observed the accumulation of
      insoluble nitrated alpha-syn in this familial disorder. Significant accumulations
      of filamentous insoluble tau protein also were detected in some brain regions of
      this patient, suggesting a role for A53T mutant alpha-syn in tau fibrillization.
      Indeed, in vitro studies of tau and alpha-syn fibrillization showed that the A53T
      mutation accelerated alpha-syn fibril formation, initiated tau assembly into
      filaments and synergistically enhanced fibrillization of both tau and alpha-syn.
      Our data implicate fibrillization of alpha-syn and tau in the pathogenesis of PD,
      and suggest that distinct amyloidogenic proteins may cross-seed each other in
      neurodegenerative diseases.

PMID- 15144855
TI  - Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of
      Niemann-Pick disease type C.
AB  - Niemann-Pick disease type C (NP-C) is a progressive and fatal neurological
      disorder characterized by intracellular accumulation of cholesterol and
      glycolipid. A Balb/c-npc1 mutant strain is a genetically authentic murine model
      of NP-C, and homozygous mice show progressive weight loss and tremor or ataxia
      until death at 12-14 weeks of age. Neuropathologically, this model is known to
      faithfully reproduce the cardinal histologic features of NP-C including neuronal
      storage, appearance of swollen axons (spheroids), and neuronal loss, although the
      cellular mechanisms of neural degeneration are largely unknown. To investigate
      the mode of neural degeneration of sensory neurons in NP-C, we studied the
      central processes of dorsal root ganglion (DRG) neurons at the level of the
      medullary dorsal column nuclei and the spinal dorsal horn with special attention
      to the ultrastructural changes of presynaptic axon terminals. The appearance of
      axonal spheroids in the dorsal column nuclei and the loss of axons in the spinal
      nerve roots were assessed quantitatively. We show that the gracile nuclei develop
      numerous axonal spheroids after only 3 weeks. At 6 and 9 weeks, dystrophic axons,
      which were separated from simple axonal spheroids by the ultrastructural presence
      of distinctive tubulo-vesicular elements, progressively increased in size and
      number. These neuropathological findings are identical to those of gracile axonal
      dystrophy (GAD) of the normal aging mouse. Presynaptic elements were exclusively
      involved in spheroid formation. The cuneate nuclei and the spinal dorsal horn
      revealed fewer axonal spheroids and only rare dystrophic changes. This was
      associated with a significant drop in the number of L4-5 dorsal root axons in NP
      C mouse at 9 weeks of age compared with controls. These results support the
      existence of a length-dependent axonopathy in the central processes of DRG
      neurons and are consistent with the view that altered axonal transport, which is
      implicated in the pathogenesis of GAD in physiological aging, may be an
      underlying mechanism in neuronal degeneration in NP-C. Clinically, the premature
      development of GAD may be responsible for ataxia, one of the early manifestations
      of this disease.

PMID- 15144856
TI  - Differential preservation of AMPA receptor subunits in the hippocampi of
      Alzheimer's disease patients according to Braak stage.
AB  - The Alzheimer's disease (AD) brain, characterized pathologically by the presence
      of senile plaques and neurofibrillary tangles, contains regions that are
      differentially prone toward development of AD pathology. Within these
      "vulnerable" regions, specific cell populations appear to be selectively
      affected; the pyramidal cells of the hippocampal subiculum subfield constitute
      such a vulnerable region. This study investigated whether the AMPA receptor
      subunit content (GluR1, GluR2, GluR2/3) within "vulnerable" vs. "resistant"
      sectors of the hippocampus is quantitatively altered with increasing AD
      neuropathology, as determined by Braak staging. We hypothesize that the glutamate
      mediated vulnerability is highly influenced by the repertoire of glutamate
      receptors expressed on hippocampal neurons. Our results indicate that AMPA
      receptor subunit proteins are relatively spared across all Braak stages in
      resistant subfields (CA2/CA3/Dentate Gyrus). However, within vulnerable sectors,
      i.e., subiculum, GluR2, and GluR2/3 protein levels decreased 63.77% and 60.60%,
      respectively, in association with Braak stages I-II and stages III-IV,
      respectively. In Braak stages V-VI, GluR2 and GluR2/3 protein levels were similar
      to those of Braak stages I-II. In contrast to GluR2 and GluR2/3, GluR1 protein
      levels were unchanged within vulnerable sectors throughout all stages of the
      disease. In interpreting these data, it may be relevant to consider that the
      GluR2 subunit impedes the flow of Ca(+2) through the AMPA receptor ion channel.
      Thus, we hypothesize that in resistant sectors, the presence of the GluR2 subunit
      may provide a neuroprotective role by limiting the flow of extracellular Ca(+2),
      whereas in vulnerable regions, the reduction of GluR2 may contribute to the
      vulnerability via a mechanism involving an increase in intracellular Ca(+2) and
      destabilization of intracellular Ca(+2) homeostasis.

PMID- 15144858
TI  - Characterization of neuronal/glial differentiation of murine adipose-derived
      adult stromal cells.
AB  - Neural tissue has limited capacity for intrinsic repair after injury, and the
      identification of alternate sources of neuronal stem cells has broad clinical
      potential. Preliminary studies have demonstrated that adipose-derived adult
      stromal (ADAS) cells are capable of differentiating into mesenchymal and non
      mesenchymal cells in vitro, including cells with select characteristics of
      neuronal/glial tissue. In this study, we extended these observations to test the
      hypothesis that murine (mu) ADAS cells can be induced to exhibit characteristics
      of neuronal and glial tissue by exposure to a cocktail of induction agents. We
      characterized the differentiation of muADAS cells in vitro using
      immunohistochemistry and immunoblotting, and examined whether these cells respond
      to the glutamate agonist N-methyl-D-aspartate (NMDA). We found that induced
      muADAS cells express proteins indicative of neuronal/glial cells, including
      nestin, GFAP, S-100, NeuN, MAP2, tau, and beta-III tubulin. Induced muADAS cells
      express gamma-aminobutyric acid (GABA), the NR-1 and NR-2 subunits of the
      glutamate receptor, GAP-43, synapsin I, and voltage-gated calcium channels.
      Finally, induced muADAS cells demonstrate decreased viability in response to
      NMDA. These findings suggest that muADAS cells can be induced to exhibit several
      phenotypic, morphologic, and excitotoxic characteristics consistent with
      developing neuronal and glial tissue.

PMID- 15144857
TI  - In vivo laminar electrophysiology co-registered with histology in the hippocampus
      of patients with temporal lobe epilepsy.
AB  - Laminar multiple microelectrodes have been developed to sample cortical and
      hippocampal activity in animals. If these measurements are adequately co
      registered with the anatomy of the region, they can yield important information
      about its function and structure. In vivo laminar electrophysiological recordings
      from the human epileptic hippocampus are rare. However, histological and
      immunohistochemical analyses are widely used to determine the structural changes
      associated with temporal lobe epilepsy (TLE). Here we present data obtained by a
      combined approach: intraoperative recording of laminar field potentials, single
      and multiple unit activity under anesthesia, accompanied by histology and
      immunohistochemistry from the same hippocampal region of epileptic patients
      undergoing temporal lobectomy for drug-resistant TLE. The stability of the
      electrophysiology and the accuracy of its co-registration with histology were
      tested successfully. We have found large field potential spikes associated with
      bursting single units in CA1. Intracortical and subdural strip recordings from
      the lateral temporal cortex showed similar field potential activation patterns. A
      prominent oscillatory activity was present in the dentate gyrus with highly
      localized field potential gradient and multiple unit activity. This pattern could
      be used as a landmark defining the position of the electrode in the hippocampus.
      Our findings indicate that some aspects of the local and network epileptiform
      activity in the hippocampal formation are likely preserved under anesthesia.
      Electrophysiological identification of the functional state of the hippocampus
      together with its local structural correlates could further enhance our
      understanding of this disease.

PMID- 15144859
TI  - Concentrations of glutamate released following spinal cord injury kill
      oligodendrocytes in the spinal cord.
AB  - We investigated in vivo in rats whether sufficient glutamate is released
      following spinal cord injury (SCI) to kill oligodendrocytes. Microdialysis
      sampling was used to establish the level of glutamate released (550 +/- 80
      microM) in the white matter during SCI. This glutamate concentration was
      administered into the spinal cords of other rats and the densities of
      oligodendrocytes remaining 24 and 72 h later determined by counting cells
      immunostained with the oligodendrocyte marker CC-1. Administration of ACSF, 4.0
      mM glutamate (estimated resulting tissue exposure 500 microM) and 10.0 mM
      glutamate by microdialysis reduced oligodendrocyte density 22%, 57%, and 74%,
      respectively, relative to normal at 24 h post-exposure. Therefore, sufficient
      glutamate is released following SCI to damage white matter. Oligodendrocyte
      densities near the fiber track were not significantly different at 72 h from 24 h
      post-exposure, so most glutamate-induced oligodendrocyte death occurs within 24 h
      after exposure. Injecting the AMPA/kainate receptor blocker NBQX into the spinal
      cord during glutamate administration reduced the glutamate-induced decrease in
      oligodendrocyte density, evidence for AMPA/kainate receptor involvement in
      glutamate-induced oligodendrocyte death. This work directly demonstrates in vivo
      that following SCI glutamate reaches concentrations toxic to white matter and
      that AMPA/kainate receptors mediate this glutamate toxicity to oligodendrocytes.

PMID- 15144860
TI  - Electrophysiology and morphometry of the Aalpha- and Abeta-fiber populations in
      the normal and regenerating rat sciatic nerve.
AB  - We studied electrophysiological and morphological properties of the Aalpha- and
      Abeta-fibers in the regenerating sciatic nerve to establish whether these fiber
      types regenerate in numerical proportion and whether and how the
      electrophysiological properties of these fiber types are adjusted during
      regeneration. Compound action potentials were evoked from isolated sciatic nerves
      12 weeks after autografting. Nerve fibers were gradually recruited either by
      increasing the stimulus voltage from subthreshold to supramaximal levels or by
      increasing the interval between two supramaximal stimuli to obtain the cumulative
      distribution of the extracellular firing thresholds and refractory periods,
      respectively. Thus, the mean conduction velocity (MCV), the maximal charge
      displaced during the compound action potential (Q(max)), the mean firing
      threshold (V(50)), and the mean refractory period (t(50)) were determined. The
      number of myelinated nerve fibers and their fiber diameter frequency
      distributions were determined in the peroneal nerve. Mathematical modeling
      applied to fiber recruitment and diameter distributions allowed discrimination of
      the Aalpha- and Abeta-fiber populations. In regenerating nerves, the number of
      Aalpha-fibers increased fourfold while the number of Abeta-fibers did not change.
      In regenerating Aalpha- and Abeta-fibers, the fiber diameter decreased and V(50)
      and t(50) increased. The regenerating Aalpha-fibers' contribution to Q(max)
      decreased considerably while that of the Abeta-fibers remained the same.
      Correlation of the electrophysiological data to the morphological data provided
      indications that the ion channel composition of both the Aalpha- and Abeta-fibers
      are altered during regeneration. This demonstrates that combining morphometric
      and electrophysiological analysis provides better insight in the changes that
      occur during regeneration.

PMID- 15144862
TI  - Co-treatment with riluzole and GDNF is necessary for functional recovery after
      ventral root avulsion injury.
AB  - Unilateral avulsion of lumbar ventral roots kills approximately 50% of injured
      motoneurons within 2 weeks of surgery. Immediate treatment involving surgical
      reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived
      neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for
      2 weeks ameliorates motoneuron death to 80% of control but combining the
      different treatment paradigms did not further enhance survival except when GDNF
      was combined with VRI. At 3 months, all combined treatments provided a
      neuroprotective effect compared to avulsion only, but the neuroprotective effect
      of surgical reimplantation alone was not maintained unless combined with riluzole
      and GDNF treatment. Analysis of regenerating motoneurons using retrograde
      labelling techniques showed that riluzole, but not GDNF, increased the number of
      dendrites per labelled motoneuron. However, when functional motor recovery was
      assessed using the BBB locomotor score and rotarod tests, only VRI animals
      treated with riluzole and GDNF application showed significantly improved
      locomotor function in both tests. Our results show that functional recovery
      appears related to a combination of enhanced dendrite formation, increased
      motoneuron survival and the neurotrophic actions of GDNF. Thus, combination
      treatment may offer a new therapeutic strategy for treating patients with
      avulsion injury.

PMID- 15144861
TI  - Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and
      Wallerian degeneration of the rat peripheral nervous system.
AB  - The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO)
      from l-arginine in response to inflammatory stimuli. NO sub-serves different
      functions from cytotoxicity to neuroprotection and triggers either necrosis or
      apoptosis. This study shows by Northern blot analysis that during experimental
      allergic neuritis (EAN), at the beginning of clinical signs, there is a transient
      extensive iNOS mRNA induction in nerve roots, in which morphology is mainly
      characterized by severe demyelination, but not in sciatic nerve, where scattered
      axonal degeneration is evident. Immunocytochemistry performed on teased nerve
      fibers and ultrastructural analysis showed that iNOS was localized in both
      inflammatory and Schwann cells, and the study of cell membrane permeability
      detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole
      peripheral nervous system (PNS). With EAN clinical progression toward spontaneous
      recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost
      all cells shifted their membrane permeability to an apoptotic phenotype, while
      necrosis persisted in sciatic nerve, until complete clinical recovery, when both
      root and nerve returned to normal. During wallerian degeneration following
      sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell
      membrane had a diffuse necrotic phenotype. These data support the hypothesis
      that, during cell-mediated demyelination, iNOS may influence Schwann cell-axon
      relationship causing axonal damage and regulating endoneurial cell life and
      death.

PMID- 15144863
TI  - Progression of temporal lobe epilepsy in the rat is associated with
      immunocytochemical changes in inhibitory interneurons in specific regions of the
      hippocampal formation.
AB  - Immunocytochemical markers of specific rat hippocampal interneuron
      subpopulations, including the calcium binding proteins parvalbumin (PV), and
      calretinin (CR) were examined in relation to the evolution of spontaneous
      seizures after electrically induced status epilepticus (SE). PV/CR/NeuN
      immunoreactive neurons were counted in the hippocampal formation at different
      time intervals after SE and related to spontaneous hippocampal discharge
      activity. Decreased PV immunoreactivity was observed within 1 day after SE in the
      hilus, pre- and parasubiculum, and in the entorhinal cortex layers II and V/VI.
      In layer III, the density of detectable PV immunoreactive neurons did not
      decrease significantly, whereas the number of surrounding principal neurons was
      extensively decreased within a week in most post-SE rats, and after 3-4.5 months
      in all rats that had developed a progressive evolution of seizures. CR
      immunoreactive neuron number decreased in all hippocampal subregions except for
      the stratum lacunosum-moleculare and the EC layer II, in which the density did
      not decrease significantly. The apparent decrease in the number of PV and CR
      immunoreactive hilar neurons was correlated with the duration of the SE and was
      most extensive in rats with a progressive form of epilepsy. The loss of CR and PV
      expression or the loss of CR- and PV-containing neurons in specific regions of
      the hippocampal formation may play a role in the progressive nature of epilepsy
      possibly via increasing the entorhinal-hippocampal activity.

PMID- 15144864
TI  - Characterisation of tectal ephrin-A2 expression during optic nerve regeneration
      in goldfish: implications for restoration of topography.
AB  - EphA receptors and their ligands the ephrin-As, expressed as retinal and tectal
      gradients, are required for the development of retino-tectal topography [Neuron
      25 (2000) 563] and its restoration during goldfish optic nerve regeneration [Mol.
      Cell. Neurosci. 25 (2004) 56]. We have reported previously that, during
      regeneration, a transient EphA3/A5 gradient is formed by differential expression
      across the entire retinal ganglion cell (RGC) population [Neurosci. Abs. 33
      (2003) 358.2; Exp. Neurol. 183 (2003) 593]. In retino-recipient tectal layers,
      ephrin-A2 is normally expressed by only a sub-population of cells, but during
      regeneration, there is a graded increase with more expressing cells caudally than
      rostrally [Exp. Neurol. 166 (2000) 196]. Here, we examine the characteristics of
      tectal ephrin-A2 expression during regeneration. We report that the level of
      ephrin-A2 expression is comparable for all ephrin-A2-positive cells in normal
      animals and during regeneration. Using double-labelling immunohistochemistry for
      ephrin-A2 and specific cell markers (NeuN for neurons, GA5 for astrocytes, NN-1
      for microglia/endothelial cells and 6D2 for oligodendrocytes), we demonstrate
      that ephrin-A2-expressing cells, as in normal animals, are exclusively neuronal.
      Moreover, double labelling with BrdU showed that ephrin-A2 is expressed in
      resident cells and not those generated during optic nerve regeneration [Brain
      Res. 854 (2000) 178, 153 (1978) 345].

PMID- 15144866
TI  - Therapeutic doses of topiramate are not toxic to the developing rat brain.
AB  - Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and
      young children may cause cognitive impairment. One of the implicated mechanisms
      is enhancement of apoptotic neuronal death, which occurs physiologically in the
      developing brain. We investigated whether topiramate, one of the newer
      antiepileptic drugs, has neurotoxic properties in the developing rat brain.
      Topiramate slightly but significantly enhanced apoptotic neuronal death in the 7
      day-old rat brain at doses of 50 mg/kg and above. These doses are several folds
      higher than reported ED(50) doses in infant rodent seizure models that respond to
      topiramate. Electron microscopy confirmed that dying neurons following topiramate
      treatment displayed the same morphological features as neurons undergoing
      physiological cell death during development. When compared to the neurotoxicity
      profile of phenytoin, valproate, and phenobarbital, the separation between the
      effective anticonvulsant dose and the neurotoxic dose was greater for topiramate
      and the neurotoxic effect was lower.

PMID- 15144865
TI  - VEGF-mediated inflammation precedes angiogenesis in adult brain.
AB  - Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis
      when infused continuously into adult rat brain tissue. In addition, VEGF has been
      shown to enhance permeability in brain vasculature. Adult rats were continuously
      infused with mouse VEGF into neocortex for up to 7 days. We studied the
      development of VEGF-induced vasculature in rat neocortex and evaluated the
      temporal expression of a wide variety of markers for inflammation and vascular
      leak in relation to the angiogenic response using immunohistochemistry and
      Western blot analysis. We report here that VEGF-mediated inflammation in brain is
      characterized by upregulation of ICAM-1 and the chemokine MIP-1alpha, as well as
      a preferential extravasation of monocytes. VEGF causes a dramatic breakdown of
      the blood-brain barrier, which is characterized by decreased investment of the
      vasculature with astroglial endfeet. Perivascular cells, in contrast, increase
      around the newly formed cerebrovasculature. In addition, breakdown of the blood
      brain barrier, leukocyte extravasation, and extracellular matrix deposition occur
      before vascular proliferation. Furthermore, administration of low doses of VEGF
      induces permeability and inflammation without appreciable vascular proliferation.

PMID- 15144867
TI  - Iris pigment epithelial cells: a possible cell source for the future treatment of
      neurodegenerative diseases.
AB  - For the treatment of neurodegenerative disorders such as Parkinson's disease cell
      or gene therapeutical options are increasingly verified. For such approaches,
      neural stem cells or astrocytes are discussed as possible cell candidates. As
      also fetal retinal pigment epithelial cells have been successfully tested for
      such therapeutical options, we investigated the potential of iris pigment
      epithelial cells as an autologous source for future cell replacement therapies.
      Using the ELISA technique, we looked for the secretion of neurotrophic factors
      under basal and stimulated conditions by iris pigment epithelial cells (IPE)
      cells and compared them with the secretion of retinal pigment epithelial cells
      (RPE) cells. As iron plays a causative role in cell death during Parkinson's
      disease, the iron-binding capacity by IPE cells was investigated. Furthermore, we
      checked the integrative capacity of IPE cells after transplantation into the
      striatum of adult rats. Our data reveal that IPE cells produce and secrete a
      variety of neurotrophic factors which can be stimulated after treatment with
      cytokines. Following transplantation, the cells can be easily detected by their
      pigmentation, survive for at least 8 weeks and as shown by electron microscopy
      integrate within the host tissue. Moreover, cells can be transduced with high
      efficiency using a third generation adenoviral vector, making them promising
      vehicles to locally deliver therapeutic proteins for the treatment of
      neurodegenerative diseases in a combined cell and gene therapeutical approach.

PMID- 15144868
TI  - Behavioral and immunohistochemical effects of chronic intravenous and
      subcutaneous infusions of varying doses of rotenone.
AB  - Mitochondrial toxins such as the complex 1 inhibitor rotenone are widely used as
      pesticides and may be present in military environments. Administration of
      rotenone can induce biochemical and histological alterations similar to those of
      Parkinson's disease in rats. However, only a subset of animals show these effects
      and it is unclear whether more subtle alterations are caused by chronic
      administration of rotenone in those animals that appear resistant to its toxic
      effects on dopaminergic nerve terminals. To address this question, vehicle or
      rotenone (2.0, 2.5, or 3.5 mg/kg/day) was administered intravenously or
      subcutaneously for 21 days to adult rats, and rotenone effects on survival, motor
      behavior, and striatal tyrosine hydroxylase immunoreactivity (TH-IR) were
      examined. Both intravenous and subcutaneous rotenone induced a dose-dependent
      decrease in survival rates. Surviving animals showed a decrease in spontaneous
      rearing. Locomotor activity and movement initiation time were also altered in
      some of the experimental groups. Confirming previous results, TH-IR in the
      striatum was markedly decreased in rats that fell ill early in the study and in a
      few of the surviving rats with high rotenone doses. However, none of the
      surviving rats receiving 2.0 mg/kg/day showed TH-IR loss reminiscent of
      Parkinson's disease, and loss of striatal TH-IR across doses was not correlated
      with motor behavior in individual rats. Thus, chronic administration of low doses
      of rotenone induces motor anomalies even in animals that do not develop
      histological signs of Parkinson's disease, indicating a pervasive neurological
      effect of moderate mitochondrial dysfunction in vivo.

PMID- 15144869
TI  - Blocking of up-regulated ICAM-1 does not prevent macrophage infiltration during
      Wallerian degeneration of peripheral nerve.
AB  - Circulating blood monocytes infiltrate into distal degenerating nerve and
      differentiate into activated macrophages that remove degenerating axonal and
      myelin debris and promote axonal regeneration. The cellular and molecular
      mechanisms responsible for this monocyte-macrophage recruitment remain largely
      unknown. Cell adhesion molecules which mediate monocyte and endothelial cell
      interactions, such as the endothelial cell adhesion molecule intercellular
      adhesion molecule-1 (ICAM-1) interaction with the monocyte adhesion molecules Mac
      1 (complement receptor type 3) and LFA-1 (lymphocyte function-associated antigen
      1), have been shown to play a critical role in mediating the transendothelial
      migration of circulating monocytes into nonneural tissues following various types
      of injury. This study investigated whether these cell adhesion molecules also
      play a critical role in mediating monocyte-macrophage infiltration during
      Wallerian degeneration of peripheral nerve. Following sciatic nerve transection,
      Mac-1- and LFA-1-positive macrophages in distal degenerating nerve increased in
      number at 2 days and peaked at 14 days before declining. The number of ICAM-1
      immunostained blood vessels increased maximally at 1 day before declining to
      baseline levels by 14 days. Three days following nerve transection, the intensity
      of ICAM-1 immunostaining on intraneural blood vessels was maximal and then
      decreased to baseline levels by 14 days. To test the role of ICAM-1 in mediating
      monocyte-macrophage recruitment, we used two complementary experimental
      strategies following a sciatic nerve transection: (1) intravenous administration
      of a rat ICAM-1-blocking monoclonal antibody and (2) ICAM-1 knockout mice. In
      both cases, the number of infiltrating monocytes-macrophages was above controls,
      which is opposite to what has been shown to occur in other tissues following
      injury.

PMID- 15144870
TI  - The role of capsaicin-sensitive afferent fibers in the lower urinary tract
      dysfunction induced by chronic spinal cord injury in rats.
AB  - The role of capsaicin-sensitive afferents in neurogenic voiding dysfunction was
      studied in chronic spinal cord injured rats (SCI). Cystometry and external
      urethral sphincter (EUS) electromyography were performed on 2 consecutive days
      after induction of urethane anesthesia in SCI rats 6-8 weeks after spinal cord
      injury. SCI rats exhibited voiding abnormalities including: non-voiding
      contractions (NVCs) before micturition, increased volume threshold (VT) for
      initiating voiding, increased amplitude and duration of voiding contractions,
      decreased voiding efficiency, increased residual urine, and changes in the
      pattern of the EUS-EMG. In SCI rats, the EUS electromyogram (EUS-EMG) consisted
      of more prominent tonic activity, shorter periods of bursting activity, and a
      reduction in the ratio of silent to active periods during bursting. These changes
      were more prominent during deeper levels of anesthesia on day 1. Capsaicin (125
      mg/kg, s.c., 4 days before urodynamic examination) reduced VT and the number of
      NVCs, decreased the amplitude and duration of voiding contractions, partially
      normalized the pattern of EUS-EMG activity, and improved the voiding efficiency
      on day 1 after induction of anesthesia but not on day 2. Capsaicin treatment
      increased the percentage of animals (from 55% to 80%) that voided on day 1. The
      results indicate that capsaicin-sensitive C-fiber bladder afferents are not
      essential for reflex micturition in SCI rats. However, these afferents do
      contribute to overactivity of the bladder and detrusor sphincter dyssynergia in
      deeply anesthetized SCI rats.

PMID- 15144871
TI  - Neuroprotective effect of rasagiline in a rodent model of Parkinson's disease.
AB  - Sprague-Dawley rats received a unilateral injection of 6-hydroxydopamine (6-OHDA)
      into the striatum and were treated daily for 6 weeks with increasing doses of
      monoamine oxidase type B inhibitor rasagiline [R(+)-N-propargyl-1-aminoindane] or
      saline (controls). Both doses of rasagiline markedly increased the survival of
      dopaminergic neurons in the lesioned substantia nigra, compared to controls (+97%
      and +119%, respectively). Treatment with the lower dose of rasagiline also
      abolished the motor stereotypies associated with nigrostriatal lesion. Our study
      supports the neuroprotective potential of chronic rasagiline administration in an
      experimental model of Parkinson's disease (PD).

PMID- 15144872
TI  - Clenbuterol retards loss of motor function in motor neuron degeneration mice.
AB  - Motor neuron degeneration (mnd) mice exhibit lysosomal accumulation of lipofuscin
      like material that is associated with progressive loss of motor function and
      strength. Motor dysfunction scores at 8.5-9 months of age were highly correlated
      with the occurrence of abnormal spinal motor neurons with eccentric nuclei,
      although the total numbers of motor neurons were not significantly reduced.
      Nuclear eccentricity is a characteristic of the axon reaction that results from
      injury and subsequent compensatory axonal sprouting indicating axonal/synaptic
      dysfunction in mnd motor neurons. Treatment with clenbuterol, a beta(2)
      adrenoceptor agonist that can enhance regeneration of motor neuron axons, opposed
      the development of motor deficits in parallel with a reduced proportion of motor
      neurons with eccentric nuclei consistent with improved synaptic function.
      Clenbuterol also opposed decreases in grip strength and muscle mass suggesting
      beta(2)-agonist treatment as a potential therapeutic modality for lipofuscinoses.

PMID- 15144873
TI  - Immediate plasticity in the motor pathways after spinal cord hemisection:
      implications for transcranial magnetic motor-evoked potentials.
AB  - The present study evaluates motor functional recovery after C2 spinal cord
      hemisection with or without contralateral brachial root transection, which causes
      a condition that is similar to the crossed phrenic phenomenon on rats. Descending
      motor pathways, including the reticulospinal extrapyramidal tract and
      corticospinal pyramidal tracts, were evaluated by transcranial magnetic motor
      evoked potentials (mMEPs) and direct cortical electrical motor-evoked potentials
      (eMEP), respectively. All MEPs recorded from the left forelimb were abolished
      immediately after the left C2 hemisection. Left mMEPs recovered dramatically
      immediately after contralateral right brachial root transection. Corticospinal
      eMEPs never recovered, regardless of transection. The facilitation of mMEPs in
      animals that had undergone combined contralateral root transection was well
      correlated with open-field behavioral motor performance. Both
      electrophysiological and neurological facilitations were significantly attenuated
      by the selective serotonin synthesis inhibitor para-chlorophenylalanine (p-CPA).
      These results suggest that serotonergic reticulospinal fibers located
      contralateral to hemisection contribute to the behavioral and
      electrophysiological improvement that immediately follows spinal cord injury
      (SCI).

PMID- 15144874
TI  - The role of p53-induced apoptosis in cerebral ischemia: effects of the p53
      inhibitor pifithrin alpha.
AB  - No neuroprotective compounds are clinically available for the treatment of
      ischemic stroke. The potential salutary effect of pifithrin alpha, a novel
      specific inhibitor of the transcription factor p53, administered 1-6 h following
      focal reversible cerebral ischemia, was investigated. Studies measuring
      histological, motor, and behavioral outcomes showed significant improvements in
      pifithrin alpha-treated animals. Pifithrin alpha reduced the number of apoptotic
      cells in the ischemic brain by inhibiting the binding of p53 to its DNA sites as
      it reduced the expression of the p53-related gene p21(WAF) without changing the
      amount of p53 protein itself.

PMID- 15144875
TI  - GDNF, Ret, GFRalpha1 and 2 in the adult rat retino-tectal system after optic
      nerve transection.
AB  - In the present study, we have studied the expression of glial cell line-derived
      neurotrophic factor (GDNF) and its receptors Ret, GFRalpha1, and GFRalpha2 in the
      retino-tectal system before and after optic nerve transection. Using retrograde
      neuronal tracing in combination with in situ hybridization, we found that Ret and
      GFRalpha1 are expressed by 13-14% of the retinal ganglion cells (RGCs). These Ret
      expressing RGCs could not be identified as belonging to any particular of the
      RG(A), RG(B), and RG(C) sub types. Ret is co-expressed with the brain-derived
      neurotrophic factor receptor TrkB in these RGCs. Optic nerve transection resulted
      in reduced Ret mRNA levels in retina, while the levels of GDNF, GFRalpha1, and 2
      mRNA increased. Administration of GDNF protein supported the axotomized RGCs.
      Analysis of normal superior colliculus (SC) did not show any expression of GDNF
      mRNA, yet GDNF mRNA levels in SC increased after injury. Together, these findings
      identify a portion of RGCs as being possible targets for pharmacological
      treatment with GDNF in a direct mode of action. The absence of detectable GDNF
      mRNA in normal SC questions the role for GDNF as being a target-derived factor
      produced in the SC for adult RGCs. The results support a function for GDNF
      locally in the retina and as part of an injury-induced system that may act to
      enhance neuroprotective and neuroregenerative responses both to endogenous GDNF
      ligands and those administered exogenously.

PMID- 15144876
TI  - Chronic nerve compression induces local demyelination and remyelination in a rat
      model of carpal tunnel syndrome.
AB  - In a previous study, we demonstrated that chronic compression of rat sciatic
      nerve, a model of compressive neuropathies, triggered dramatic Schwann cell
      proliferation and concurrent apoptosis. Importantly, this Schwann cell response
      occurred before there are signs of overt axonal pathology, raising the question
      of whether there are alterations in axonal myelination in the areas of the nerve
      in which Schwann cell apoptosis and proliferation occur. Here, we use nerve
      teasing techniques and unbiased stereology to assess myelination in nerves after
      1 and 8 months of compression. Evaluations of myelin thickness and axonal
      diameter (AD) using design-based, unbiased stereology revealed alterations in
      myelin structure that indicate remyelination, specifically a dramatic decrease in
      the average internodal length (IL) and an increase in the proportion of axons
      with thin myelin sheaths. The mean IL was reduced after 1 month of chronic nerve
      injury with no further decrease in IL at 8 months. There was limited change in
      average axonal diameter at both 1 and 8 months. Measures of myelin thickness
      revealed not only a greater than 6-fold increase in the number of axons with very
      thin (<5 microm thickness) myelin sheaths, but also a proportional decrease in
      the number of axons with the thick myelin sheaths characteristic of normal nerve.
      These results confirm that an early consequence of chronic nerve compression
      (CNC) is local demyelination and remyelination, which may be the primary cause of
      alterations in nerve function during the early period post-compression.

PMID- 15144878
TI  - Control of multidigit grasping in Parkinson's disease: effect of object property
      predictability.
AB  - We examined the extent to which subjects with Parkinson's disease (PD) modulate
      normal fingertip forces during five-digit grasping based on the object's center
      of mass (CM). We also tested the effect of trial-to-trial predictability of CM
      location on the distribution of all fingertip forces relative to thumb force. Ten
      right-handed subjects with PD (OFF and ON medication) and 10 healthy age-matched
      control subjects participated. Subjects lifted a manipulandum that measured
      normal forces exerted by each digit. The CM location was changed from trial-to
      trial either in an unpredictable (random) or predictable (blocked) order.
      Discriminant analysis and information theory were used to quantify the extent to
      which force-sharing patterns could be discriminated as a function of CM location.
      All subjects modulated fingertip normal forces as a function of CM location
      regardless of its predictability, although larger forces were employed when its
      location was unpredictable. However, in controls, normal force modulation of
      individual fingers to the object's CM location occurred over a greater range of
      forces when the CM location was predictable than when it was unpredictable. In
      contrast, subjects with PD exhibited a similar force modulation to CM location
      regardless of its predictability. There was a clearer discrimination of force
      sharing patterns when the CM location was predictable for controls but not for
      subjects with PD OFF medication. Medication improved the time course of normal
      force modulation to CM location. These results indicate that subjects with PD
      maintained the ability to modulate individual fingertip forces to the object's
      physical properties. Nevertheless, subjects with PD did not benefit from the a
      priori knowledge of object CM location to the same extent as controls. These
      findings support the notion that PD affects the ability to use anticipatory
      control mechanisms.

PMID- 15144877
TI  - In vivo magnetic resonance tracking of olfactory ensheathing glia grafted into
      the rat spinal cord.
AB  - Engraftment of olfactory ensheathing cells (OEC), a unique type of glia required
      for olfactory nerve growth throughout life, has been shown to foster axonal
      regeneration in different types of CNS and PNS injuries. However, a lack of
      suitable markers of OEC has hindered studies assessing survival and function of
      OEC grafts following transplantation. The aim of this study was to examine the
      possible usefulness of superparamagnetic iron oxide nanoparticles
      (magnetodendrimers) as a label to allow in vivo tracking of grafted OEC by MR
      imaging and to determine temporal and spatial migration of OEC in normal and
      injured rat spinal cords, including the possibility of such cells to cross a
      complete spinal cord injury zone. We found that labeled OEC were readily
      detectable in vivo by MR imaging for at least 2 months. Labeled OEC migrated
      extensively in normal spinal cord as shown by MRI and histological markers. In
      contrast, OEC showed limited migration in transected spinal cord and were not
      able to cross the transection gap. Furthermore, iron-containing hemorrhage
      products confounded interpretation of MR contrast patterns in the injured spinal
      cord. We conclude that (1) MR imaging is useful for noninvasive observation of
      cell migration dynamics after grafting in vivo, although interpretation in severe
      injuries should be cautious, and that (2) OEC migratory and thus regeneration
      enhancing ability is limited when confronted with the glial scar of a transected
      spinal cord.

PMID- 15144879
TI  - Relatively low levels of calpain expression in juvenile rat correlate with less
      neuronal apoptosis after spinal cord injury.
AB  - Approximately 5% of spinal cord injuries in the US occur in patients younger than
      16 years. These young patients have an increased mortality within the 24 h after
      trauma but have a greater capacity for functional recovery than adults,
      suggesting age-related differences in injury tolerance. Unfortunately, the
      response of the developing cord to secondary injury has not been thoroughly
      investigated. Calpain, a Ca(2+)-dependent protease, has been implicated in the
      pathogenesis of spinal cord injury (SCI) in rats. Our current investigation
      revealed that following SCI, calpain upregulation was qualitatively less in the
      21-day-old rats than in adult rats, as shown by immunofluorescent labeling.
      Decreased levels of TUNEL+ neurons were also noted in juvenile rat spinal cord,
      indicating that the developing cord may have an increased resistance to injury.

PMID- 15144881
TI  - Toward cell replacement therapy.

PMID- 15144880
TI  - Differential change in mRNA expression of p75 and Trk neurotrophin receptors in
      nucleus gracilis after spinal nerve ligation in the rat.
AB  - In peripheral neuropathy (PN), dorsal column (DC) fibers that synapse in the
      nucleus gracilis (NuGr) mediate expression of mechanical allodynia and have
      increased expression of brain-derived neurotrophic factor (BDNF). Neurotrophins
      (NTs) are implicated in pathology or repair in PN. To assess NTs in the NuGr in
      PN, mRNA expression of BDNF, nerve growth factor (NGF), and NT receptors TrkA,
      TrkB, and p75 was determined 1 week after ligation of L5 and L6 spinal nerves
      (SNL). Laser capture microdissection was used to collect NuGr tissue followed by
      reverse-transcription (RT)-PCR. TrkA, TrkB, and NGF mRNA levels decreased,
      whereas p75 mRNA increased, in ipsilateral SNL NuGr compared with SHAM; BDNF was
      undetectable. Decreased Trk mRNA may result in decreased NT activity in the NuGr.
      The p75 receptor influences Trk activity and cell survival, thus its role in PN
      warrants further investigation.

PMID- 15144883
TI  - In vitro induction of adult hepatic progenitor cells into insulin-producing
      cells.
AB  - Organ-specific stem cells are the natural progenitors in tissue regeneration and
      possess plasticity to differentiate into specialized cells in adult tissues.
      Small hepatocytes (SHCs) identified in the adult liver are one such cell type.
      Here we show that SHCs, which are capable of self-renewal and differentiation
      into hepatocytes, can be induced to generate insulin-producing cells under
      appropriate culture conditions. These differentiated cells express pancreatic
      beta cell differentiation-related transcripts and hepatocyte differentiation
      related transcripts, as shown by reverse-transcription PCR/nested PCR. In
      addition, enforced expression of the homeodomain transcription factor Pdx1 in
      these cells contributes to enhancement of insulin release in response to insulin
      secretagogues. These results indicate that the SHCs described here have the
      ability to differentiate into insulin-producing cells, and further support the
      idea that engineering to generate insulin-secreting cells could provide a useful
      resource for future therapies for diabetes mellitus.

PMID- 15144884
TI  - Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression.
AB  - Pdx-1 plays important roles both in the development of the pancreas and in
      maintaining pancreatic beta cell function. However, the role of Pdx-1 in the
      regulation of insulin release is not well established. We previously demonstrated
      that Pdx-1 overcomes the defect in insulin release from the insulin-producing
      cells derived from small hepatocytes (SHCs). Insulin secretion is regulated in
      vivo by the sequential events triggered by the increase of intracellular Ca(2+)
      concentration in response to high glucose concentration. In the present study, we
      identified a new target of Pdx-1 involved in insulin release. Pdx-1 positively
      regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)
      sensor that plays a central role in insulin release) through Pdx-1-binding sites
      within the 3' regulatory region of the Syt1 gene. We further demonstrated the
      essential role of Pdx-1 in insulin secretion by the gene knock-down strategy.
      Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the
      levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. Our data
      indicate that Pdx-1 might contribute to the regulation of insulin release by
      promoting Syt1 expression in vivo, and provide useful information for future
      therapy of diabetes mellitus.

PMID- 15144885
TI  - alpha-Tocopheryl succinate inhibits proliferation of mesothelioma cells by
      selective down-regulation of fibroblast growth factor receptors.
AB  - alpha-Tocopheryl succinate (alpha-TOS), a redox-silent analogue of vitamin E,
      inhibits malignant mesotheliomas (MM) in a pre-clinical model. Here we
      investigated the underlying mechanism. Exposure of MM cells to alpha-TOS
      triggered apoptosis at higher and inhibited proliferation at lower
      concentrations, while this effect was not observed in non-malignant mesothelial
      cells. Sub-apoptotic doses of alpha-TOS caused down-regulation of fibroblast
      growth factor receptor-1 (FGFR1) selectively in MM cells, while the effect on
      FGFR2 was only marginal. FGF1 and FGF2 enhanced MM cell proliferation that was
      suppressed by alpha-TOS. Over-expression of E2F1, a transcriptional factor of
      FGFR1, but not its dominant-negative counterpart, partially blocked the
      inhibitory activity of alpha-TOS on MM cell proliferation. Our data suggest a
      novel mechanism by which a clinically intriguing agent selectively suppresses
      proliferation of cancer cells, as shown here for the untreatable mesotheliomas.

PMID- 15144887
TI  - A novel calcium-binding peptide from the cuticle of the crayfish, Procambarus
      clarkii.
AB  - A novel peptide named calcification-associated peptide (CAP)-2 was isolated from
      the exoskeleton of the crayfish, Procambarus clarkii. CAP-2 consists of 65 amino
      acid residues and has a 44% sequence identity with CAP-1 characterized
      previously. It has a chitin-binding domain observed in many arthropod cuticle
      proteins. CAP-2 showed inhibitory activity on calcium carbonate precipitation and
      chitin-binding ability. A CAP-2 cDNA was cloned using RT-PCR and RACE and the
      open reading frame encoded a precursor peptide consisting of a signal peptide and
      CAP-2. RT-PCR revealed that CAP-2 mRNA was exclusively expressed in the epidermal
      tissue during the postmolt stage, the site and stage being associated with
      calcification. Calcium-binding assay using recombinant CAP-2 revealed that this
      peptide had affinity for calcium ions with a Kd value of about 1 mM. All these
      results suggest that CAP-2 serves as a nucleator or a regulator in the
      calcification of the exoskeleton.

PMID- 15144886
TI  - Hypoxia augments TNF-alpha-mediated endothelin-1 release and cell proliferation
      in human optic nerve head astrocytes.
AB  - The effect of hypoxia (24 h) on TNF-alpha-mediated release of endothelin-1 (ET-1)
      from human optic nerve head astrocytes (hONAs) and TNF-alpha- and ET-1-induced
      hONA proliferation was determined. ET-1 synthesis and release was quantitated
      using ELISA while TNF-alpha (10 nM)- and ET-1 (100 nM)-mediated hONA
      proliferation was assessed by CellTiter 96 aqueous one-solution cell
      proliferation assay, respectively. hONAs appeared to be more rounded with fewer
      processes following 24 h hypoxia compared to thodr seen in normoxia. Hypoxia
      enhanced TNF-alpha-mediated ET-1 synthesis and release (by 5-fold) and also
      significantly increased TNF-alpha- and ET-1-mediated hONA proliferation. PD142893
      (1 microM), an ET(A/B) receptor antagonist, blocked ET-1-mediated hONA
      proliferation both under normoxia and hypoxia, while doing so only under normoxia
      following TNF-alpha treatment. Also, U0126 (10 microM; an upstream ERK1/2
      inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and
      partially blocked the same in hypoxia. These results demonstrate for the first
      time that hONAs secrete ET-1 and that TNF-alpha and hypoxia can regulate its
      levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF
      alpha and ET-1. These agonist-mediated effects following hypoxia could contribute
      to astroglial activation as seen in glaucomatous optic nerve heads.

PMID- 15144888
TI  - Identification of two novel clusters of ultrahigh-sulfur keratin-associated
      protein genes on human chromosome 11.
AB  - We analyzed two novel clusters of keratin-associated protein (KAP) genes on human
      chromosome 11 (11p15.5 and 11q13.5) in which we identified two known human KRTAP5
      genes, KerA (=KRN1) and KerB, and nine novel KRTAP5 family genes. RT-PCR analysis
      of these KAP genes showed preferential expression in human hair root, suggesting
      these gene products are required for hair formation. Based on the deduced amino
      acid sequences, all these KAP proteins were classified into an ultrahigh-sulfur
      (UHS) type KAP with high cysteine content (> 30 mol%). These KAPs also showed
      high glycine and serine contents (average 24.30 and 21.13 mol%, respectively),
      distinguishing from other UHS/HS KAP families located on human chromosomes 17 and
      21. Dot-matrix analysis revealed a significant similarity between these two KAP
      gene clusters. We postulated a mechanism by which these two KAP gene clusters are
      generated via genomic duplication of a primordial gene cluster followed by
      genetic modification during evolution.

PMID- 15144889
TI  - Conditional activation of RhoA suppresses the epithelial to mesenchymal
      transition at the primitive streak during mouse gastrulation.
AB  - Gastrulation is a pivotal event of mouse early embryogenesis. In telencephalin
      (TLCN)-Cre mice carrying the Cre recombinase gene inserted into the translational
      initiation site of the TLCN gene, Cre-mediated recombination took place at the
      postimplantation stage. To examine the role of RhoA signaling in early
      embryogenesis, we produced Rho36 mice carrying constitutively active RhoA(G14V)
      gene inducible by Cre recombinase and crossed with TLCN-Cre mice. In doubly
      transgenic embryos at the gastrulation stage, there appeared an abnormal bulge of
      cells protruded from the primitive streak region into the amniotic cavity. The
      bulged cell mass expressed the epiblast marker gene Oct3 and E-cadherin, but not
      the primitive streak marker gene T except for the basal portion. These results
      suggest that the conditional activation of RhoA signaling suppressed the
      epithelial to mesenchymal transition at the primitive streak during mouse
      gastrulation.

PMID- 15144891
TI  - Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial
      cells.
AB  - The upregulation of endothelial cell MCP-1 production by ox-LDL is a major
      initiating event in atherogenesis. HDL and PON1 retard the oxidation of LDL and
      therefore may retard endothelial cell MCP-1 production. The endothelial cell line
      EAhy926 was incubated with ox-LDL in the presence and absence of HDL and PON1 and
      the production of MCP-1 was measured by ELISA. Human HDL and PON1 significantly
      inhibited the in vitro oxidation of LDL and completely prevented the ox-LDL
      induced increase in MCP-1 production by endothelial cells. Ostrich HDL that does
      not contain PON1 was unable to prevent LDL-oxidation or the production of MCP-1
      by endothelial cells. PON1 attenuates the ox-LDL induced MCP-1 production by
      endothelial cells. This is one, early, mechanism by which PON1 may be anti
      atherogenic.

PMID- 15144890
TI  - Efficient in vitro transduction of naive murine B cells with lentiviral vectors.
AB  - The aim of this study was to determine the impact of lentiviral transduction on
      primary murine B cells. Studying B cell activities in vivo or using them for
      tolerance induction requires that the cells remain unaltered in their biological
      behavior except for expression of the transgene. As we show here, murine B cells
      can efficiently be transduced by lentiviral, VSV-G-pseudotyped vectors without
      the necessity of prior activation. Culture with LPS gave enhanced transduction
      efficiencies but led to the upregulation of CD86 and proliferation of the cells.
      Transduction of naive B cells by lentiviral vectors was dependent on multiplicity
      of infection and did not lead to a concomitant activation. Furthermore, the
      transduced cells could be used for studies in the NOD mouse system without
      altering the onset of diabetes. We conclude that lentiviral gene transfer into
      naive B cells is a powerful tool for manipulation of B cells for therapeutic
      applications.

PMID- 15144892
TI  - Homogeneous real-time detection and quantification of nucleic acid amplification
      using restriction enzyme digestion.
AB  - A method for real-time fluorescent detection and quantification of nucleic acid
      amplification using a restriction endonuclease was developed. In this homogeneous
      system detection is mediated by a primer containing a reporter and quencher
      moiety at its 5' terminus separated by a short section of DNA encoding a
      restriction enzyme recognition sequence. In the single stranded form, the signal
      from the fluorescent reporter is quenched due to fluorescence resonance energy
      transfer. However, as the primer becomes incorporated into a double stranded
      amplicon, a restriction enzyme present in the reaction cleaves the DNA linking
      the reporter and quencher, allowing unrestricted fluorescence of the reporter. To
      test this system, a primer specific for the E6 gene of human papilloma virus
      (HPV) 16 was combined with the cleavable energy transfer label and used to
      amplify HPV16 positive DNA. In the presence of the thermally stable restriction
      enzyme BstNI, the reporter system was found to generate a fluorescent signal in
      proportion to the amount of template DNA. In addition to this direct format, the
      reporter primer was also used to monitor and quantify the amplification of other
      sequences. This was accomplished by using primers that contain a tag sequence
      complementary to the reporter oligonucleotide.

PMID- 15144893
TI  - LY294002 inhibits interferon-gamma-stimulated inducible nitric oxide synthase
      expression in BV2 microglial cells.
AB  - The current study examined the potential involvement of phosphatidylinositol 3
      phosphate kinase (PI3K) in interferon-gamma (IFN-gamma)-stimulated nitric oxide
      (NO) generation in BV2 murine microglial cells. We found that LY294002, a PI3K
      inhibitor, markedly reduced IFN-gamma-induced morphological changes, NO
      production, and cell death. The inhibitory effect of LY294002 on NO generation
      may be mediated through specific inhibition of signal transducer and activator-1
      (STAT1) and NF-kappaB, which are activated by IFN-gamma. Induction of the mRNA
      for IFN-gamma-mediated interferon response factor (IRF-1) and inducible protein
      10 (IP-10) was not significantly affected by LY294002, indicating that
      suppression of PI3K may not be sufficient for downregulation of these genes.
      Although it remains unclear how PI3K signaling is involved in IFN-gamma-mediated
      inflammatory reactions in the brain, our findings provide some insight into the
      inflammatory mechanisms of IFN-gamma in the brain and suggest that regulators of
      the PI3K pathway may act as anti-inflammatory agents in microglia.

PMID- 15144894
TI  - Functions of pancreatic beta cells and adipocytes in bombesin receptor subtype-3
      deficient mice.
AB  - We previously reported that mice lacking bombesin receptor subtype-3 (BRS-3)
      exhibit mild late-onset obesity and glucose intolerance [Nature 390 (1997) 160].
      To examine the mechanism by which glucose intolerance is developed in these mice,
      we studied insulin release and proinsulin biosynthesis in isolated pancreatic
      islets and glucose uptake and facilitative glucose transporter (GLUT)-4
      translocation in adipose tissues. Although islet insulin contents and the size
      and number of islets of Langerhans in BRS-3-deficient mice decreased, there was
      no difference in glucose-stimulated insulin release and proinsulin biosynthesis
      between BRS-3-deficient and wild-type control mice. In contrast, adipose tissues
      exhibited a marked difference: the uptake of [(14)C]2-deoxy-D-glucose by
      adipocytes isolated from BRS-3-deficient mice was not stimulated by 10(-7)M
      insulin addition, and membrane fractionation analysis showed that GLUT4 was
      barely detected in the fraction of plasma membrane in BRS-3-deficient mice in the
      presence of 10(-7)M insulin. Quantitative reverse transcription-PCR (RT-PCR)
      showed that mRNA levels of GLUT4, insulin receptor, insulin receptor substrate
      (IRS)-1 and IRS-2, syntaxin 4, SNAP23, and VAMP-2 in adipose tissues of BRS-3
      deficient mice were unchanged compared with those in wild-type control mice. We
      concluded that impaired glucose metabolism observed in BRS-3-deficient mice was
      mainly caused by impaired GLUT4 translocation in adipocytes.

PMID- 15144896
TI  - Renal carcinoma cells undergo apoptosis without oligonucleosomal DNA
      fragmentation.
AB  - Apoptotic DNA fragmentation minimizes the risk of transferring genetic
      information from apoptotic cancer cells to the neighboring cells. We have
      reported previously that caspase-deficient human renal cell carcinoma (RCC) lines
      were almost completely resistant to apoptosis in response to cytotoxic agents. In
      the present report we examined apoptotic process in caspase competent RCC-91
      cells. Apoptosis in RCC-91 cells was accompanied by activation of caspases-3 and 
      9; cleavage of PARP and DFF45 proteins; typical apoptotic nuclei fragmentation
      and mitochondrial collapse. Nevertheless, DNA in these cells was not degraded
      into oligonucleosomal fragments compared to control Jurkat cells. Expression of
      caspase-activated DNase, DFF40 accountable for characteristic ladder pattern was
      easily detectable in Jurkat but not renal cancer cells, providing one possible
      explanation for the lack of oligonucleosomal DNA fragmentation in apoptotic RCC
      cells. Lack of typical DNA fragmentation indicates a potential threat of
      transferring genetic information from one tumor cell to another or to the
      neighboring healthy cells.

PMID- 15144895
TI  - A prostanoid receptor EP4 agonist enhances ectopic bone formation induced by
      recombinant human bone morphogenetic protein-2.
AB  - The anabolic effects of prostaglandin E(2) on bone are effected through the
      activation of EP4, a G protein-coupled receptor. In the present study, we
      examined the effects of a prostanoid receptor-selective agonist (ONO-4819) in an
      experimental system of ectopic bone formation using recombinant human bone
      morphogenetic protein-2 (rhBMP-2). Collagen pellets containing rhBMP-2 were
      implanted onto the back muscles of mice and then treated with ONO-4819
      administered every 8 h by subcutaneous injection. The ossicles elicited
      ectopically by rhBMP-2 in mice treated with 30 microg/kg ONO-4819 were
      significantly larger in size and had a higher bone mineral density and bone
      mineral content when compared to the controls. We also noted that the anabolic
      effect of ONO-4819 was seen only in the early phase of the rhBMP-2-induced bone
      forming process. These experimental results indicate that the EP4 receptor
      agonist enhances the rhBMP-2-induced bone formation through a selective effect on
      early stage mesenchymal cells, which in turn may result in increased
      responsiveness of the host animals to rhBMP-2.

PMID- 15144897
TI  - NuRD complex component Mi-2beta binds to and represses RORgamma-mediated
      transcriptional activation.
AB  - RORgamma is a nuclear receptor that binds to DNA motifs as a monomer to
      constitutively activate target genes. RORgamma plays an important role in
      thymocyte development and lymph node organogenesis, while the regulation of
      RORgamma-mediated transcriptional activation is currently unclear. The purpose of
      this study was to identify other nuclear proteins that interact with RORgamma. A
      yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted
      in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting
      protein. This interaction was confirmed by GST pull-down assays. This interaction
      occurred within the middle regulatory region (amino acids 719-1164) of Mi-2beta.
      Transfection of Gal4-RORgamma into HeLa cells resulted in constitutive
      transactivation of the MH100-tk-luc reporter. The addition of Mi-2beta resulted
      in a dramatic 50% decrease in Gal4-RORgamma-mediated transactivation. These data
      demonstrate that RORgamma forms a protein-protein interaction with the regulatory
      region of Mi-2beta, resulting in inhibition of RORgamma transcriptional activity.
      These results may provide evidence as to how RORgamma-mediated transactivation is
      regulated by other nuclear proteins.

PMID- 15144899
TI  - Functional expression of TWEAK in human hepatocellular carcinoma: possible
      implication in cell proliferation and tumor angiogenesis.
AB  - TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF family whose
      transcripts are expressed in various human tissues. Since TWEAK has a variety of
      biological activities, we investigated TWEAK sensitivity, expression, and
      physiological role in human hepatocellular carcinomas (HCCs). Tweak receptor was
      detected in four kinds of HCC cells. TWEAK significantly promoted cell
      proliferation and induced nuclear factor-kappaB activation in all HCC cells.
      Surprisingly, we found that HCC cells constitutively express TWEAK. In addition,
      soluble TWEAK was detected in culture medium. We found that TWEAK also promotes
      cell proliferation and induces the secretion of IL-8 and MCP-1 in human umbilical
      vein endothelial cell. Finally, culture medium from Sh-Hep1 cells incubated with
      anti-TWEAK antibody significantly inhibited endothelial cell tube formation. In
      conclusion, these results indicate that TWEAK might play a critical role in HCC
      cellular proliferation using both autocrine and paracrine mechanisms, and
      modulate tumor-related angiogenesis.

PMID- 15144898
TI  - HIV protease inhibitor nelfinavir inhibits replication of SARS-associated
      coronavirus.
AB  - A novel coronavirus has been identified as an etiological agent of severe acute
      respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for
      clinical use, we screened a set of compounds that included antiviral drugs
      already in wide use. Here we report that the HIV-1 protease inhibitor,
      nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV).
      Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection.
      Expression of viral antigens was much lower in infected cells treated with
      nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed
      that nelfinavir could decrease the production of virions from Vero cells.
      Experiments with various timings of drug addition revealed that nelfinavir
      exerted its effect not at the entry step, but at the post-entry step of SARS-CoV
      infection. Our results suggest that nelfinavir should be examined clinically for
      the treatment of SARS and has potential as a good lead compound for designing
      anti-SARS drugs.

PMID- 15144900
TI  - Inverse correlation between jasmonic acid and salicylic acid during early wound
      response in rice.
AB  - This study presents a kinetic analysis of the response to wounding in rice
      plants. In particular, jasmonic acid, salicylic acid, and lipoxygenase activity
      were measured in leaves of wounded rice plants during the early tillering phase.
      The results show that endogenous jasmonic acid transiently increases to a maximum
      30 min after wounding (jasmonic acid burst) and lipoxygenase activity increases
      after the jasmonic acid burst, but not after the second smaller peak of
      endogenous jasmonic acid 23 h after wounding. In contrast, endogenous salicylic
      acid decreases during the jasmonic acid burst, such that the kinetic profiles of
      jasmonic acid and salicylic acid are inversely correlated during the early
      response to wounding. It is proposed here that the increase in endogenous
      jasmonic acid and the decrease in endogenous salicylic acid may contribute for
      establishing the efficient negative cross-talk between jasmonic acid and
      salicylic acid signaling pathways during the early response to wounding in rice.

PMID- 15144901
TI  - Expression and activity of the cytolethal distending toxin of Helicobacter
      hepaticus.
AB  - Helicobacter hepaticus, a causal agent of hepatocarcinoma in mice, exhibits a
      cytolethal distending toxin activity. The three subunits of this holotoxin, CdtA,
      CdtB, and CdtC, and three CdtB mutants were produced as recombinant histidine
      tagged proteins by using an in vitro cell-free protein expression system. We
      found that the presence of the three H. hepaticus Cdt subunits is required for
      cellular toxicity and that only a C-terminal CdtB mutation abolishes the activity
      of the complex. In vitro, H. hepaticus CdtB exhibits a DNase activity which is
      also abolished by this C-terminal CdtB mutation. These results suggest that the
      effect of H. hepaticus CDT probably involves the DNase activity of CdtB.

PMID- 15144902
TI  - A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt
      heterodimer.
AB  - We have identified an enhancer responsible for induction by 3-methylcholanthrene
      in the upstream region of the CYP1A2 gene. The enhancer does not contain the
      invariant core sequence of XREs that are binding sites for the Ah receptor (AhR)
      and Arnt heterodimer. The enhancer did not show any inducible expression in Hepa
      1-derived cell lines, C4 and C12, deficient of Arnt and AhR, respectively. On the
      other hand, bacterially expressed AhR-Arnt heterodimer could not bind to the
      enhancer. Mutational analysis of the enhancer revealed that a repeated sequence
      separated by six nucleotides is important for expression. A factor binding
      specifically to the enhancer was found by using gel shift assays. Bacterially
      expressed AhR-Arnt heterodimer interacted with the factor. A dominant negative
      mutant of the AhR to XRE activated the enhancer. Collectively, these results
      demonstrate that a novel induction mechanism is present in which the AhR-Arnt
      heterodimer functions as a coactivator.

PMID- 15144903
TI  - Endogenous hydrogen sulfide regulation of myocardial injury induced by
      isoproterenol.
AB  - Previous work has shown that the endogenous cystathionine gamma-synthase
      (CSE)/hydrogen sulfide (H(2)S) pathway participates in the regulation of cardiac
      contraction. We hypothesized that the pathway might participate in the
      pathophysiological regulation of ischemic heart disease. Isoproterenol injection
      of rat hearts induced a myocardial ischemic injury model, with reduced myocardial
      and plasma H(2)S levels, decreased CSE activity, and upregulated CSE gene
      expression. Exogenous administration of the H(2)S donor NaHS reduced the
      mortality rate; increased left-ventricular pressure development and left
      ventricular-end systolic pressure; and decreased left-ventricular-end diastolic
      pressure (LVEDP) and subendocardial necrosis, capillary dilatation, leukocytic
      infiltration, fibroblast swelling, and fibroblastic hyperplasia. As well,
      production of lipid peroxidation, including myocardial malondialdehyde (MDA), and
      plasma MDA and conjugated diene, was reduced. Oxidative stress injury is an
      important mechanism of isoproterenol-induced myocardial injury. In vitro
      experiments revealed that NaHS might antagonize myocyte MDA production by oxygen
      free radicals and that NaHS directly scavenged hydrogen peroxide and superoxide
      anions. Our results suggest that the endogenous CSE/H(2)S pathway contributes to
      the pathogenesis of isoproterenol-induced myocardial injury. Administration of
      exogenous H(2)S effectively protects myocytes and contractile activity, at least
      by its direct scavenging of oxygen-free radicals and reducing the accumulation of
      lipid peroxidations.

PMID- 15144904
TI  - An intron promotes the anti-bcr-abl activities of a retrovirally expressed
      ribozyme in chronic myeloid leukemia cells.
AB  - Ribozymes have been developed to cleave the bcr-abl transcripts and thereby
      suppress transforming activities of chronic myelogenous leukemia (CML) cells.
      However, the intracellular efficacy of vector-dependent ribozymes usually depends
      in part on their expression cassettes, which may affect their intracellular
      trafficking and distribution. In order to test effects of an intron in pre-fusion
      ribozyme on the anti-bcr-abl activities in CML cells, retroviral vectors
      harboring ribozyme expression cassettes with (RzI) or without (Rz) an intron
      encoding sequence were used to transduce K562 cells. In terms of both reduction
      of the target bcr-abl mRNA and suppression of colony formation in soft agar and
      xenograft growth on SCID mice, the anti-bcr-abl efficacy of the RzI fusion
      ribozyme was significantly superior to that of Rz. These results also correlate
      with more cytoplasmic accumulation of the RzI fusion ribozymes than that of the
      Rz. This study suggests activities of a RNA polymerase II-driven fusion ribozyme
      against its targeted spliced mRNA are improved by incorporating an intron in its
      pre-splicing transcript. Noticeably, the improvement is contributed in part by
      subcellular co-localization.

PMID- 15144906
TI  - Thymol: a classical small-molecule compound that has a dual effect (potentiating
      and inhibitory) on myosin.
AB  - The effect of thymol on the ATPase activity of myosin subfragment-1 (S1) and on
      the contractile properties of skinned skeletal muscle fibers was studied. At
      concentrations of 1.5-2 mM, thymol activated the S1 ATPase substantially and the
      actin-activated S1 ATPase modestly. At the same concentrations, the isometric
      force of skinned skeletal muscle fibers was modestly suppressed (11% at 2 mM).
      However, the kinetic parameters of contraction were suppressed more: the velocity
      of shortening and the rate of force redevelopment after shortening were
      suppressed by 43% and 31% at 2 mM, respectively. Thus, among other small-molecule
      inhibitors, thymol is unique in that it has opposite effects on the enzymatic
      activity and kinetic parameters of contraction. Thymol may serve as a potent tool
      for studying the mechanism of coupling between the ATPase reaction and
      contraction in muscle.

PMID- 15144905
TI  - Functional mapping of tissue-specific elements of the human alpha-fetoprotein
      gene enhancer.
AB  - Serum alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC) patients
      and expression of the protein in cultured HCC cell lines are highly variable.
      These observations may arise from features correlated with tissue-specific
      expression of the gene. Extremely strong and potent liver-specific enhancer
      activity is confined from -4.1 to -3.3 kb upstream to the human AFP gene in
      contrast with that of the rodent which exists in three widely separated regions.
      To understand the tissue-specific expression of AFP, we examined cis-acting
      elements in the enhancer. Results revealed binding sites for selected liver
      enriched transcription factors (LETFs) in both domains A (-4120 to -3756 bp) and
      B (-3492 to -3300 bp) of the gene. These sites included: one hepatocyte nuclear
      factor (HNF)-1 and HNF-4, two HNF-3, and two C/EBP binding sites in domain A. An
      adjacent domain B contained one HNF-3 site and three C/EBP sites plus a
      previously identified HNF-1 site. Each of these elements alone has the ability to
      stimulate heterogeneous promoter activity in a dose-dependent manner when
      transfected into AFP producing cells. A comparative study showed that the
      presence of two HNF-1 and one HNF-4 site is a characteristic feature of human but
      not rodent AFP enhancer. The mRNA levels of the liver-enriched transcription
      factors (LETFs) were variable in individual HCC cell lines and together with
      silencer activities may underlie differential expression of the AFP gene.

PMID- 15144907
TI  - Rab7b, a novel lysosome-associated small GTPase, is involved in monocytic
      differentiation of human acute promyelocytic leukemia cells.
AB  - Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late
      endosomal stages of the endocytic pathway. Here we report the cloning and
      characterization of a novel Rab7-like GTPase, which shares highest homology with
      Rab7 and thus is designated as Rab7b. Northern blot analysis shows that Rab7b
      mRNA is expressed in human heart, placenta, lung, skeletal muscle, and peripheral
      blood leukocyte. RT-PCR or Western blot analysis of Rab7b expression shows that
      Rab7b is selectively expressed in monocytes, monocyte-derived immature dendritic
      cells (DCs), and promyeloid or monocytic leukemia cell lines. In the peripheral
      blood, Rab7b is specifically detected in CD14(+) cells, but not in CD4(+),
      CD8(+), CD19(+) or CD56(+) cells. When immature DCs are matured with
      lipopolysaccharide (LPS), Rab7b expression is gradually downregulated, while
      Rab7b is upregulated when monocytes are activated by LPS treatments. In acute
      promyelocytic leukemia (APL) HL-60 and NB4 cell lines, Rab7b expression is
      upregulated after phorbol myristate acetate (PMA)-induced monocytic
      differentiation. By immunofluorescence confocal microscopy, we demonstrate that
      Rab7b is associated with lysosomal organelles. Our data suggest that Rab7b is a
      lysosome-localized monocytic cell-specific small GTPase, and is involved in PMA
      induced APL cell differentiation and possibly in regulation of monocyte
      functions.

PMID- 15144908
TI  - Effect of short-term treatment with inhaled corticosteroid on airway wall
      thickening in asthma.
AB  - PURPOSE: Computed tomography studies demonstrate thickening of the asthmatic
      airway wall and its relation to disease severity. We evaluated the effect of
      inhaled corticosteroid on this phenomenon. METHODS: Cross-sectional images of the
      right upper lobe apical segmental bronchus were obtained by helical computed
      tomography in 45 corticosteroid-naive patients with persistent asthma and 28
      healthy controls. Airway wall thickness was measured as airway wall area
      normalized to body surface area. Computed tomography, pulmonary function, and
      serum levels of eosinophil cationic protein were examined before and after
      treatment with beclomethasone (800 microg/d for 12 weeks). RESULTS: Before
      treatment, airway wall thickness was greater in asthma patients than in controls
      (P <0.0001). After treatment, it decreased by 11% (P <0.001) but remained high (P
      <0.0001 vs. control); the serum level of eosinophil cationic protein decreased,
      and airflow obstruction was reduced, but not to the level in controls. The
      decrease in wall thickness was associated with a decrease in the serum level of
      eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced
      expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to
      disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness
      was related to disease duration (r = 0.45, P = 0.003) and remaining airflow
      obstruction. CONCLUSION: Wall thickening of asthmatic central airways responds
      partially to inhaled corticosteroid therapy and may reflect an overall reduction
      in airway inflammation. "Unresponsive components," possibly involving structural
      changes, may increase in the absence of inhaled corticosteroid treatment,
      potentially leading to chronic airflow obstruction.

PMID- 15144910
TI  - Lansoprazole in the treatment of functional dyspepsia: two double-blind,
      randomized, placebo-controlled trials.
AB  - PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in
      patients with functional dyspepsia remains controversial. This study was designed
      to compare the efficacy of lansoprazole with placebo in relieving upper abdominal
      discomfort in patients with functional dyspepsia. METHODS: We enrolled 921
      patients with functional dyspepsia (defined as persistent or recurrent upper
      abdominal discomfort during the prior 3 months) and moderate upper abdominal
      discomfort on at least 30% of screening days; none of the patients had
      predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence
      of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion.
      Patients were assigned randomly to receive lansoprazole 15 mg (n = 305),
      lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients
      recorded the frequency and severity of symptoms in daily diaries. RESULTS: At
      week 8, significantly (P <0.001) greater mean reductions in the percentage of
      days with upper abdominal discomfort were reported in patients treated with
      lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo
      (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg
      (44%) reported complete symptom resolution (defined as no episodes of upper
      abdominal discomfort in the 3 days before the study visit) at 8 weeks than did
      placebo-treated patients (29%, P <0.001). Improvement of upper abdominal
      discomfort, however, was seen only in patients who had at least some symptoms of
      heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30
      mg, is significantly better than placebo in reducing symptoms of persistent or
      recurrent upper abdominal discomfort accompanied by at least some symptoms of
      heartburn.

PMID- 15144909
TI  - Case management for patients with poorly controlled diabetes: a randomized trial.
AB  - PURPOSE: To evaluate the effects of a collaborative case management intervention
      for patients with poorly controlled type 2 diabetes on glycemic control,
      intermediate cardiovascular outcomes, satisfaction with care, and resource
      utilization. METHODS: We conducted a randomized controlled trial at two
      Department of Veterans Affairs Medical Centers involving 246 veterans with
      diabetes and baseline hemoglobin A(1C) (HbA(1C)) levels >or=7.5%. Two nurse
      practitioner case managers worked with patients and their primary care providers,
      monitoring and coordinating care for the intervention group for 18 months through
      the use of telephone contacts, collaborative goal setting, and treatment
      algorithms. Control patients received educational materials and usual care from
      their primary care providers. RESULTS: At the conclusion of the study, both case
      management and control patients remained under poor glycemic control and there
      was little difference between groups in mean exit HbA(1C) level (9.3% vs. 9.2%;
      difference = 0.1%; 95% confidence interval: -0.4% to 0.7%; P = 0.65). There was
      also no evidence that the intervention resulted in improvements in low-density
      lipoprotein cholesterol level or blood pressure control or greater
      intensification in medication therapy. However, intervention patients were
      substantially more satisfied with their diabetes care, with 82% rating their
      providers as better than average compared with 64% of patients in the control
      group (P = 0.04). CONCLUSION: An intervention of collaborative case management
      did not improve key physiologic outcomes for high-risk patients with type 2
      diabetes. The type of patients targeted for intervention, organizational factors,
      and program structure are likely critical determinants of the effectiveness of
      case management. Health systems must understand the potential limitations before
      expending substantial resources on case management, as the expected improvements
      in outcomes and downstream cost savings may not always be realized.

PMID- 15144912
TI  - Clinician identification of chronically ill patients who have problems paying for
      prescription medications.
AB  - PURPOSE: Little is known about whether health care providers are effectively
      identifying patients who have difficulty covering the costs of out-of-pocket
      prescription medications. We examined whether and how providers are identifying
      chronically ill adults who have potential problems paying for prescription
      medications. METHODS: We conducted a cross-sectional survey of a national sample
      of 4050 adults aged 50 years or older who use prescription medications for at
      least one of five chronic health conditions. The primary outcome measure was
      patient report of being asked by a doctor or nurse in the prior 12 months whether
      the patient could afford the prescribed medication. The measures of prescription
      cost burden were cost-related underuse of medications, cutting back on other
      necessities to pay for medications, and worries about medication costs. We
      adjusted for patient income, education, race/ethnicity, age, sex, health status,
      number of prescribed medications, pharmacy benefits, frequency of outpatient
      visits, having a regular health care provider, and sampling weights. RESULTS: In
      the weighted analyses, 16% (547/4050) of respondents reported that they had been
      asked about potential problems paying for a prescribed medication. Only 360 (24%)
      of the 1499 respondents who reported one or more burdens from out-of-pocket
      medication costs reported being asked this question. After adjusting for
      potential confounders, patients who had cut back on medication use or other
      necessities to cover payments were no more likely than other patients to be asked
      about the ability to pay for prescription medications. Concerns about medication
      costs, being a racial/ethnic minority, taking seven or more prescription
      medications, and having no prescription coverage were independently associated
      with a greater likelihood of being asked about possible problems with
      prescription costs. CONCLUSION: Few chronically ill patients who are at risk of
      or experiencing problems related to prescription medication costs report that
      their clinicians had asked them about possible medication payment difficulties.

PMID- 15144911
TI  - Accelerated decline in lung function and impaired reversibility with salbutamol
      in asthmatic patients with chronic hepatitis C virus infection: a 6-year follow
      up study.
AB  - PURPOSE: Chronic hepatitis C virus (HCV) infection may have adverse effects on
      pulmonary function in patients with chronic obstructive pulmonary disease. This
      prospective study was designed to determine whether chronic HCV infection affects
      decline in lung function and airway responses to salbutamol in asthmatic
      patients. METHODS: Interferon alpha (6 MIU three times a week for 6 months) was
      given to 55 HCV-positive asthmatic patients, 18 of whom had a virologic response
      to interferon. Pre- and postbronchodilator forced expiratory volume in 1 second
      (FEV(1)) and reversibility with salbutamol or oxitropium at years 1, 3, and 6
      after interferon therapy were examined. RESULTS: We found a significant decrease
      in pre- and postbronchodilator FEV(1) from year 1 to years 3 and 6 only in
      interferon nonresponders. Reversibility with salbutamol at years 3 and 6 was
      significantly lower in interferon nonresponders than in HCV-negative patients (P
      <0.0001) and interferon responders (P <0.0001). Moreover, there was a steep
      decline in reversibility with salbutamol during the follow-up period only in
      interferon nonresponders. In contrast, reversibility with oxitropium at years 3
      and 6 was significantly higher in interferon nonresponders than in HCV-negative
      patients and interferon responders, and there was a steep increase in
      reversibility with oxitropium only in interferon nonresponders. In addition,
      declines in the diffusing capacity of the lung for carbon monoxide during follow
      up were significantly greater in interferon nonresponders than in HCV-negative
      patients and interferon responders. CONCLUSION: Chronic HCV infection is
      associated with an accelerated decline in lung function and impaired
      reversibility with salbutamol among asthmatic patients who do not respond to
      interferon therapy.

PMID- 15144913
TI  - An evidence-based medicine approach to beta-blocker therapy in patients with
      cirrhosis.
AB  - Disease management strategies have gained attention in recent years because of
      their potential to improve health-related quality of life and prevent excessive
      resource use. Despite recognition as an important cause of mortality, cirrhosis
      with portal hypertension has not been widely discussed as a condition amenable to
      planned care management. Given the effect of variceal hemorrhage as the most
      immediate life-threatening complication of portal hypertension, a number of high
      quality controlled clinical trials have confirmed the efficacy of beta-blocker
      therapy for primary and secondary prophylaxis. Despite the existence of practice
      guidelines that incorporate this information, specific clinical scenarios that
      demand consideration for beta-blocker therapy have not been well described. In
      this article, a number of hypothetical patient-based cases drawn from the
      authors' experiences are utilized to illustrate these issues.

PMID- 15144914
TI  - Severe head trauma in patients with unexplained central hypothyroidism.

PMID- 15144915
TI  - Cases from the Osler Medical Service at Johns Hopkins University.
AB  - PRESENTING FEATURES: A 70-year-old African American man was admitted with a
      history of fever, chills, and malaise of several days' duration. His past medical
      history was notable for end-stage renal disease requiring hemodialysis, coronary
      artery disease, and aortic stenosis requiring a bioprosthetic aortic valve
      replacement. On the day of admission, the patient was noted to have a shaking
      chill while undergoing dialysis through his catheter and was admitted to the
      hospital. He complained of pain at the catheter insertion site, shortness of
      breath, and dyspnea on exertion, but denied chest pain. On physical examination,
      the patient had a temperature of 100.4 degrees F, with a heart rate of 64 beats
      per minute, blood pressure of 127/72 mm Hg, and an oxygen saturation of 97% on
      room air. He was a mildly obese man in no apparent distress. He had shotty
      cervical lymphadenopathy and a right subclavian dialysis catheter in place, with
      erythema and pus at the entry site. His jugular venous pressure was 10 cm H(2)O.
      Lung examination showed bibasilar rales. Heart sounds were normal, with no rub or
      gallop. He had a 2/6 systolic ejection murmur best heart at the left sternal
      border as well as a 3/6 holosystolic murmur at the apex that radiated to his left
      axilla. Examination of the abdomen and extremities was unremarkable. The
      patient's neurological examination was unremarkable, and he was alert and
      oriented to person, place, and time. Laboratory studies showed an elevated white
      blood cell count of 16,700 cells/microL. His blood urea nitrogen level was 43
      mg/dL and his serum creatinine level was 4.9 mg/dL. Multiple blood cultures grew
      methicillin-resistant Staphylococcus aureus. An admission, chest radiograph
      showed no infiltrate. An admission electrocardiogram showed normal sinus rhythm
      with first degree atrioventricular block, left anterior fascicular block, and
      left ventricular hypertrophy. shows rhythm strips from lead II electrocardiograms
      5 months before admission (top), on admission (middle) and 5 days after admission
      (bottom). What is the diagnosis?

PMID- 15144916
TI  - The computed tomographic scan: a new tool to monitor asthma treatment?

PMID- 15144917
TI  - Still no magic bullets: pursuing more rigorous research in quality improvement.

PMID- 15144918
TI  - Functional dyspepsia: the devil in the details.

PMID- 15144919
TI  - "Connective tissue" between panic disorder and dysautonomia.

PMID- 15144921
TI  - Hyperacute respiratory failure causing transient left ventricular dysfunction.

PMID- 15144922
TI  - Primary actinomycosis of the humerus: a quite unusual form.

PMID- 15144923
TI  - Correlation of thrombotic thrombocytopenic purpura disease activity with von
      Willibrand factor-cleaving protease level in ulcerative colitis.

PMID- 15144925
TI  - Pneumopericardium after manual strangulation.

PMID- 15144926
TI  - Tracheal puncture revisited.

PMID- 15144924
TI  - A paraganglioma parasitizing the left circumflex coronary artery.

PMID- 15144927
TI  - The future of continuing medical education.

PMID- 15144929
TI  - Pharmacology of carvedilol.
AB  - Carvedilol is a third-generation, neurohormonal antagonist with multiple
      activities. It blocks both beta(1)- and beta(2)-adrenergic receptors, enhances
      vasodilation via alpha(1)-adrenergic blockade, and, at high concentrations, has
      ion channel-blocking activities. Carvedilol lacks sympathomimetic activity. In
      addition to these well-known properties, carvedilol has a number of ancillary
      activities, including antioxidant, anti-inflammatory, and antiapoptotic
      properties. Together, they contribute to the clinical efficacy of carvedilol in a
      broad spectrum of patient types and may also confer a range of cardioprotective
      benefits.

PMID- 15144931
TI  - Landmark study: the Carvedilol Post-Infarct Survival Control in Left Ventricular
      Dysfunction Study (CAPRICORN).
AB  - The benefit of beta-blockers for secondary prevention of death and reinfarction
      after myocardial infarction (MI) has been conclusively demonstrated in randomized
      clinical trials. Before the Carvedilol Post-Infarct Survival Control in Left
      Ventricular Dysfunction Study (CAPRICORN)-a multicenter, multinational, double
      blind, randomized, placebo-controlled trial that enrolled 1,959 patients who had
      an acute MI and a left ventricular ejection fraction of <==0.40-it was not known
      whether beta-blockers confer additional benefit when used in the context of
      modern post-MI management (eg, fibrinolytic therapy and primary percutaneous
      transluminal coronary angioplasty, aspirin, and angiotensin-converting enzyme
      inhibitors). Patients in CAPRICORN were treated with a maximum dose of 25 mg bid
      and observed until 633 validated primary end points had occurred. Because the
      overall mortality was lower than had been predicted, a co-primary end point was
      adopted that included the original primary end point (all-cause mortality) plus
      the first of the prespecified secondary end points (all-cause mortality or
      cardiovascular hospitalizations). A significant 23% reduction in the original
      primary end point of all-cause mortality was observed. A total of 340 (35%)
      patients died or had a cardiovascular hospitalization in the carvedilol group
      versus 367 (37%) in the placebo group. Therefore, the revised primary end point
      of all-cause mortality or cardiovascular hospitalization was reduced by 8%, which
      was not statistically significant. Significant reductions in cardiovascular
      mortality, nonfatal MI, and the combination of all-cause mortality or nonfatal MI
      were observed. Although statistical significance for the revised primary end
      point was not reached, CAPRICORN has an important role in guiding future use of
      beta-blockers in the early post-MI period.

PMID- 15144930
TI  - beta-Blockers in hypertension: is carvedilol different?
AB  - Most studies assessing the effects of beta-blockers were carried out with
      traditional, beta(1)-selective beta-blockers, such as metoprolol and atenolol.
      Pathophysiologic and pharmacologic studies have documented that not all beta
      blockers are created equal. In particular, the pharmacologic and clinical
      profiles of the newer, vasodilating beta-blockers, such as carvedilol, have been
      shown to differ from those of the traditional beta-blockers. These differences,
      although relevant in the younger patient with hypertension, are particularly
      important in elderly patients in whom traditional beta-blockers may not be as
      effective or as well tolerated as the newer vasodilating agents.

PMID- 15144932
TI  - Cardiac remodeling in coronary artery disease.
AB  - Cardiac remodeling is a central mechanism of heart failure progression in
      patients with coronary artery disease (CAD). The remodeling effect of beta
      blockade with carvedilol has been studied in patients with left ventricular
      dysfunction after myocardial infarction and in patients with chronic heart
      failure of ischemic etiology. Carvedilol has been found to prevent progressive
      adverse ventricular remodeling in both conditions. This effect is concordant with
      the improvement in long-term clinical outcomes established for carvedilol in such
      patients. Thus, ventricular remodeling appears to be an important treatment
      target in patients with CAD and is likely to mediate at least part of the
      clinical improvement achieved with carvedilol.

PMID- 15144935
TI  - Carvedilol prospective randomized cumulative survival (COPERNICUS) trial:
      carvedilol in severe heart failure.
AB  - The impact of carvedilol on the survival of patients with severe heart failure
      was examined in the Carvedilol Prospective Randomized Cumulative Survival
      (COPERNICUS) trial. The trial recruited 2,289 patients with symptoms at rest or
      on minimal exertion despite therapy with angiotensin-converting enzyme inhibitors
      and a left ventricular ejection fraction of < or = 0.25. After an average follow
      up period of 10.4 months, mortality was reduced by 34% in the carvedilol group.
      Carvedilol also reduced the number of days spent in the hospital for any cause by
      27% and the number of days spent in the hospital for heart failure by 40%.
      Patients in the carvedilol group felt better and were less likely to have a
      serious adverse event. The benefits of carvedilol appeared early and were
      detected during the up-titration period.

PMID- 15144934
TI  - Landmark studies: the Australia/New Zealand Heart Failure Collaborative Group
      (ANZ) Trial and the US Carvedilol Trials Program.
AB  - The safety, tolerability, and hemodynamic effects of carvedilol in patients with
      heart failure were first studied in the mid 1990s. Positive results in these
      early trials led to 5 prospective, randomized, double-blind, placebo-controlled
      trials-the Australia/New Zealand Heart Failure Collaborative Group (ANZ) study
      and the 4 component studies of the US Carvedilol Heart Failure Trials Program.
      These studies were conducted to determine the clinical impact of long-term
      carvedilol therapy. Findings from these trials showed that carvedilol is a
      powerful therapy (1) in patients with chronic heart failure caused by left
      ventricular (LV) systolic dysfunction, improving morbidity and mortality; and (2)
      in patients with symptomatic heart failure, improving LV ejection fraction,
      improving clinical status, and slowing disease progression, resulting in
      reduction of the combined risk of hospitalization and mortality. This article
      discusses the design, results, and clinical implications of these trials.

PMID- 15144936
TI  - Commentary on the Carvedilol or Metoprolol European Trial (COMET).
AB  - beta-Adrenergic blockade is commonly and successfully used to treat chronic heart
      failure. Until recently, few data were available on which to base selection of a
      particular beta-blocking agent. The Carvedilol or Metoprolol European Trial
      (COMET) provides evidence that beta-blockers are not interchangeable. The trial
      compared carvedilol, a nonselective beta-blocker with alpha-adrenergic blocking
      and numerous ancillary activities, with metoprolol tartrate. In comparison to
      metoprolol tartrate, significant reductions in all-cause mortality and
      cardiovascular mortality were observed with carvedilol. These data indicate that
      cardiovascular benefit may be obtained from switching patients from metoprolol
      tartrate to carvedilol.

PMID- 15144937
TI  - Ventricular remodeling in heart failure and the effect of beta-blockade.
AB  - Left ventricular (LV) remodeling has an important role in the progression of
      cardiovascular disease. An understanding of the process of LV remodeling has led
      to greater knowledge of the pathophysiology of heart failure. Drug therapies that
      slow or reverse the remodeling process seem to have favorable natural history
      effects in short-term and long-term therapy. Angiotensin-converting enzyme (ACE)
      inhibitors have been associated with a significant reduction in mortality, and
      the effect of beta-blockers on the remodeling process has now been studied across
      much of the spectrum of severity in patients with heart failure. beta-Blockade
      seems to add favorable and independent effects on the post-myocardial infarction
      remodeling process over and above those of ACE inhibitors. A combination of both
      drugs shows the greatest reduction in mortality (ie, the most favorable reverse
      remodeling). Differences in their effect on remodeling have been recently shown
      among the beta-blockers. Several studies and a meta-analysis suggest that
      carvedilol may be more favorable to outcome, having the most effect on LV
      remodeling.

PMID- 15144938
TI  - Advantages of a third-generation beta-blocker in patients with diabetes mellitus.
AB  - beta-Blocker use improves outcomes even more for the patient with diabetes
      mellitus than for the patient without diabetes with a history of acute myocardial
      infarction or coronary artery disease. beta-Blockers facilitate shifting the
      metabolism of the myocardium away from free fatty acid toward glucose
      utilization, thereby reducing the cardiac workload and myocardial ischemia. beta
      Blockers are also able to reverse the fetal gene induction program to reverse
      myocardial remodeling and improve ventricular function. Side effects of beta
      blockers in the patient with diabetes include increased insulin resistance with
      worsening glycemic control, elevated triglyceride levels, and lowered levels of
      high-density lipoprotein cholesterol. Increased frequency of hypoglycemia and its
      lack of recognition can also be a problem in the insulin-deficient patient but is
      a minimal problem with the patient with type 2 diabetes. In addition,
      vasoconstriction, caused by unopposed alpha-activity, can worsen peripheral
      vascular disease. However, carvedilol, a nonselective beta-blocker with
      vasodilating and insulin-sensitizing properties, can largely circumvent these
      problems and is the ideal beta-blocker for the patient with diabetes.

PMID- 15144939
TI  - Role of carvedilol in atrial fibrillation: insights from clinical trials.
AB  - Atrial fibrillation affects approximately 2 million people in the United States
      and is a common comorbidity among patients with heart failure. Clinical studies
      indicate that the benefits of the beta-blocker carvedilol in patients with heart
      failure extend to patients with heart failure complicated by atrial fibrillation.
      The results of the Carvedilol in Atrial Fibrillation Evaluation (CAFE) trial
      provide support that carvedilol has incremental benefit when added to digoxin for
      the management of atrial fibrillation in patients with heart failure. Additional
      recent studies suggest that carvedilol may be useful in managing postsurgical
      atrial fibrillation and also may prevent recurrence of atrial fibrillation among
      patients who undergo cardioversion.

PMID- 15144940
TI  - Tolerability of carvedilol in heart failure: clinical trials experience.
AB  - An extensive clinical trials database now exists to support the therapeutic
      efficacy of beta-blockers in systolic heart failure. However, concerns remain
      about the tolerability of these agents. These concerns relate to perceived
      complexity in initiation and uptitration, risk of worsening heart failure
      clinical status, and delay in beneficial effects on outcomes. All of the above
      concerns are thought especially relevant in patients with advanced disease.
      However, these perceptions are not borne out in the controlled clinical trial
      experience or in open-label studies and postmarketing surveillance programs with
      carvedilol. Specifically, in clinical studies, discontinuation rates (because of
      adverse events), serious adverse event rates, mean achieved dose, and percentage
      reaching target dose strongly suggest good tolerability. This is especially
      notable, considering that beta-blockade is used in addition to other background
      neurohormonal antagonists, such as angiotensin-converting enzyme inhibitors.
      Furthermore, tolerability in the everyday community setting also appears to be
      high. Carvedilol, specifically, is also well tolerated during initiation of
      therapy, with fewer withdrawals for heart failure during the first 8 weeks of
      uptitration, and no delay in the accrual of beneficial clinical outcomes, as
      observed in the Carvedilol Prospective Randomized Cumulative Survival
      (COPERNICUS) study. Thus, in contrast to widely held perceptions about
      tolerability of beta-blockade in heart failure, carvedilol appears to be an
      extremely well-tolerated agent, even during initiation and in the most advanced
      patients.

PMID- 15144941
TI  - Special considerations for carvedilol use in heart failure.
AB  - Remarkable improvements in morbidity and mortality caused by heart failure have
      been realized because of a greater understanding of the pathobiologic mechanisms
      of left ventricular dysfunction and the subsequent application of neurohormonal
      antagonism to the heart failure milieu. The median survival of patients with
      chronic heart failure has greatly increased with the use of effective medical
      therapy that includes angiotensin-converting enzyme inhibitors and beta-blockers,
      especially carvedilol. Still to be addressed is the issue of clinical trials that
      under represent special populations of patients who are affected with heart
      failure (eg, the elderly, women, and African Americans). Even though heart
      failure may be a somewhat different illness in etiology, epidemiology, or
      responsiveness to medical therapy for each of these groups, it is of utmost
      importance that patients affected by heart failure be treated with agents that
      have been shown to be of benefit in the major controlled clinical trials in heart
      failure.

PMID- 15144942
TI  - Practical guidelines to optimize effectiveness of beta-blockade in patients
      postinfarction and in those with chronic heart failure.
AB  - Antiadrenergic therapy reduces the risks of death and major morbidity in patients
      postinfarction and in those with chronic heart failure. Despite the common
      perception, these benefits are not attributable to a class effect, and clinical
      trials reveal evidence of specific agents that provide clinical advantages. To
      optimize patient outcome in the postinfarction setting, propranolol or timolol
      should be used in the setting of preserved ventricular function, and carvedilol
      should be used in patients with impaired ventricular function, with or without
      clinical evidence of heart failure. Patients with chronic heart failure are at
      lower risk of death when treated with carvedilol, which is also associated with a
      lower incidence of developing diabetes mellitus-related adverse events. This
      article reviews the scientific evidence for the hierarchy of antiadrenergic
      agents and addresses practical issues associated with initiation of therapy and
      long-term management.

PMID- 15144943
TI  - Predischarge initiation of carvedilol in patients hospitalized for decompensated
      heart failure.
AB  - The use of beta-blockers for the treatment of heart failure in the United States
      is inadequate, despite available data and current guidelines that support their
      use. The Initiation Management Predischarge: Process for Assessment of Carvedilol
      Therapy for Heart Failure (IMPACT-HF) study was designed to determine whether
      initiation of beta-blockade before hospital discharge is safe and effective in
      improving the 60-day use of beta-blockers in patients with heart failure. IMPACT
      HF compared the strategy of the initiation of carvedilol before patients were
      discharged versus usual care (Heart Failure Society of America guidelines
      recommend waiting 2 to 4 weeks after hospitalization for heart failure before
      initiating beta-blocker therapy) in 363 randomized patients with heart failure.
      The entry criteria were non-restrictive to ensure inclusion of patients
      reflective of the general heart failure population. The primary end point of the
      study (the number of patients treated with any beta-blocker at 60 days) was
      statistically significantly higher in the predischarge group versus the
      postdischarge group (91.2% vs 73.4%, respectively). Based on the study's results,
      predischarge initiation may be a successful strategy to improve the use of beta
      blocker therapy for patients with heart failure.

PMID- 15144944
TI  - Role of in-hospital initiation of carvedilol to improve treatment rates and
      clinical outcomes.
AB  - Patients with heart failure face a very high risk of hospitalization and
      mortality. Despite compelling scientific evidence that beta-blockers reduce
      hospitalizations and mortality in patients with heart failure, this lifesaving
      therapy continues to be underused. Studies in a variety of clinical settings have
      documented that a significant proportion of patients with heart failure are not
      receiving treatment with this guideline-recommended, evidence-based therapy when
      physicians are guided by conventional care. A similar treatment gap has been
      documented for lipid-lowering therapy in patients with coronary artery disease.
      It has been demonstrated that initiation of lipid-lowering and other
      cardiovascular protective medications before hospital discharge for
      atherosclerotic cardiovascular events results in a marked increase in treatment
      rates, improved long-term patient compliance, and better clinical outcomes. This
      has led to national guidelines being revised to endorse this approach as the
      standard of care. Recent studies demonstrate that carvedilol can be safely and
      effectively initiated in patients with heart failure before hospital discharge
      and that this improves clinical outcomes. Adopting in-hospital initiation of
      carvedilol as the standard of care for patients hospitalized with heart failure
      could dramatically improve treatment rates-thus substantially reducing the risk
      of future hospitalizations and prolonging life in the many patients with heart
      failure hospitalized each year.

PMID- 15144945
TI  - Intratumoral hypoxia, radiation resistance, and HIF-1.
AB  - Failure to achieve complete remission after radiation therapy is a predictor of
      patient mortality, and hypoxic cancer cells are more likely to survive radiation
      therapy. Recent studies have shown that radiation-induced endothelial cell death
      results in secondary tumor cell killing. In this issue of Cancer Cell, now
      provide evidence that radiation induces HIF-1-mediated expression of VEGF and
      bFGF in tumor cells, which promotes endothelial cell survival.

PMID- 15144946
TI  - Engineered embryonic endothelial progenitor cells as therapeutic Trojan horses.
AB  - While the hematogenic contribution of circulating endothelial cells to tumor
      angiogenesis is not entirely understood, one can exploit this phenomenon as a
      therapeutic strategy. In this issue of Cancer Cell, show that murine embryonic
      endothelial progenitor cells preferentially home to sites of lung metastases,
      evade immunological rejection, and can exert a bystander antitumor effect when
      modified to contain a suicide gene construct that activates a prodrug. Treatment
      with the prodrug led to improved survival in syngeneic and nonsyngeneic tumor
      bearing mouse models. The conceptual advance put forward by this study might
      result in translational applications.

PMID- 15144947
TI  - Cysteine cathepsins (proteases)--on the main stage of cancer?
AB  - Cysteine cathepsins are involved in degradation of extracellular matrix,
      facilitating growth, invasion, and metastasis of tumor cells, in tumor
      angiogenesis, in apoptosis, and in events of inflammatory and immune responses.
      In this issue of Cancer Cell, demonstrate association of increased cathepsins
      activity with angiogenic vasculature and invasive fronts of carcinomas during
      tumorigenesis in transgenic mouse models using activity-based chemical probes and
      in vivo imaging. Moreover, this study shows that a broad-spectrum cysteine
      cathepsin inhibitor effectively blocks several stages of tumorigenesis in the
      RIP1-Tag2 transgenic mouse model, offering new therapeutic opportunities in
      cancer treatment.

PMID- 15144948
TI  - Predictive factors for epidermal growth factor receptor inhibitors--the bull's
      eye hits the arrow.
AB  - Studies have shown that epidermal growth factor receptor (EGFR) signaling is
      important to normal development and neoplastic transformation, and that EGFR
      inhibition reduces cancer cell proliferation. The promising response rates of the
      EGFR inhibitor gefitinib in patients with chemotherapy-refractory non-small cell
      lung cancer (NSCLC) led to its approval for clinical use. However, there was
      little understanding of why gefitinib was effective in only some NSCLC patients.
      Two recent studies have identified somatic mutations in EGFR that confer its
      sensitivity to gefitinib in vitro and correlate strongly with patients' clinical
      response to the inhibitor.

PMID- 15144949
TI  - The development of proteasome inhibitors as anticancer drugs.
AB  - The ubiquitin-proteasome pathway plays a central role in the targeted destruction
      of cellular proteins, including cell cycle regulatory proteins. Because these
      pathways are critical for the proliferation and survival of all cells, and in
      particular cancerous cells, proteasome inhibition is a potentially attractive
      anticancer therapy. Based on encouraging cytotoxic activity, bortezomib was the
      first proteasome inhibitor to be evaluated in clinical trials. Efficacy and
      safety results from a phase 2 clinical trial contributed to approval of
      bortezomib for use in patients with relapsed and refractory multiple myeloma who
      have received at least 2 prior therapies and have demonstrated disease
      progression on their last therapy.

PMID- 15144950
TI  - Focus on nasopharyngeal carcinoma.

PMID- 15144951
TI  - Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role
      of reoxygenation, free radicals, and stress granules.
AB  - Through a poorly understood mechanism, tumors respond to radiation by secreting
      cytokines capable of inhibiting apoptosis in endothelial cells, thereby
      diminishing treatment response by minimizing vascular damage. We reveal here that
      this pathway is governed by a major angiogenesis regulator, HIF-1. Following
      radiotherapy, tumor reoxygenation leads to: (1) nuclear accumulation of HIF-1 in
      response to reactive oxygen, and (2) enhanced translation of HIF-1-regulated
      transcripts secondary to stress granule depolymerization. The resulting increase
      in HIF-1-regulated cytokines enhances endothelial cell radioresistance.
      Inhibiting postradiation HIF-1 activation significantly increases tumor
      radiosensitivity as a result of enhanced vascular destruction. These data
      describe novel pathways contributing significantly to our understanding of HIF-1
      regulation which may be major determinants of tumor radiosensitivity, potentially
      having high clinical relevance.

PMID- 15144952
TI  - Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis
      during multistage tumorigenesis.
AB  - Tumors develop through successive stages characterized by changes in gene
      expression and protein function. Gene expression profiling of pancreatic islet
      tumors in a mouse model of cancer revealed upregulation of cathepsin cysteine
      proteases. Cathepsin activity was assessed using chemical probes allowing
      biochemical and in vivo imaging, revealing increased activity associated with the
      angiogenic vasculature and invasive fronts of carcinomas, and differential
      expression in immune, endothelial, and cancer cells. A broad-spectrum cysteine
      cathepsin inhibitor was used to pharmacologically knock out cathepsin function at
      different stages of tumorigenesis, impairing angiogenic switching in progenitor
      lesions, as well as tumor growth, vascularity, and invasiveness. Cysteine
      cathepsins are also upregulated during HPV16-induced cervical carcinogenesis,
      further encouraging consideration of this protease family as a therapeutic target
      in human cancers.

PMID- 15144953
TI  - Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis.
AB  - Inappropriate transcriptional repression involving histone deacetylases (HDACs)
      is a prominent cause for the development of leukemia. We now identify faulty
      expression of a specific mediator of transcriptional repression in a solid tumor.
      Loss of the adenomatosis polyposis coli (APC) tumor suppressor induces HDAC2
      expression depending on the Wnt pathway and c-Myc. Increased HDAC2 expression is
      found in the majority of human colon cancer explants, as well as in intestinal
      mucosa and polyps of APC-deficient mice. HDAC2 is required for, and sufficient on
      its own to prevent, apoptosis of colonic cancer cells. Interference with HDAC2 by
      valproic acid largely diminishes adenoma formation in APC(min) mice. These
      findings point toward HDAC2 as a particularly relevant potential target in cancer
      therapy.

PMID- 15144954
TI  - Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein
      p53 from HDM2-mediated degradation.
AB  - Nucleophosmin (NPM, B23) is an abundant nucleolar phosphoprotein involved in
      ribosome biogenesis, and interacts with tumor suppressor proteins p53 and Rb.
      Here we show that NPM is a UV damage response protein that undergoes
      nucleoplasmic redistribution and regulates p53 and HDM2 levels and their
      interaction. By utilizing RNAi approaches and analyses of endogenous and
      ectopically expressed proteins, we demonstrate that NPM binds HDM2 and acts as a
      negative regulator of p53-HDM2 interaction. Viral stress, enforced by expression
      of Kaposi's sarcoma virus K cyclin, causes NPM redistribution, K cyclin-NPM
      association, and p53 stabilization by dissociation of HDM2-p53 complexes. The
      results demonstrate novel associations of HDM2 and K cyclin with NPM and
      implicate NPM as a crucial controller of p53 through inhibition of HDM2.

PMID- 15144955
TI  - Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic
      lung metastases after intravenous delivery.
AB  - We show that mouse embryonic endothelial progenitor cells (eEPCs) home
      preferentially to hypoxic lung metastases when administered intravenously. This
      specificity is inversely related to the degree of perfusion and vascular density
      in the metastasis and directly related to local levels of hypoxia and VEGF. Ex
      vivo expanded eEPCs that were genetically modified with a suicide gene
      specifically and efficiently eradicated lung metastases with scant patent blood
      vessels. eEPCs do not express MHC I proteins, are resistant to natural killer
      cell-mediated cytolysis, and can contribute to tumor vessel formation also in
      nonsyngeneic mice. These results indicate that eEPCs can be used in an allogeneic
      setting to treat hypoxic metastases that are known to be resistant to
      conventional therapeutic regimes.

PMID- 15144956
TI  - Molecular classification of head and neck squamous cell carcinomas using patterns
      of gene expression.
AB  - The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely
      based upon the tumor size and location and the presence of lymph node metastases.
      Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA
      microarrays allowed categorization of these tumors into four distinct subtypes.
      These subtypes showed statistically significant differences in recurrence-free
      survival and included a subtype with a possible EGFR-pathway signature, a
      mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype
      with high levels of antioxidant enzymes. Supervised analyses to predict lymph
      node metastasis status were approximately 80% accurate when tumor subsite and
      pathological node status were considered simultaneously. This work represents an
      important step toward the identification of clinically significant biomarkers for
      HNSCC.

PMID- 15144957
TI  - Synthetic lethal targeting of MYC by activation of the DR5 death receptor
      pathway.
AB  - The genetic concept of synthetic lethality provides a framework for identifying
      genotype-selective anticancer agents. In this approach, changes in cellular
      physiology that arise as a consequence of oncogene activation or tumor suppressor
      gene loss, rather than oncoproteins themselves, are targeted to achieve tumor
      selectivity. Here we show that agonists of the TRAIL death receptor DR5 potently
      induce apoptosis in human cells overexpressing the MYC oncogene, both in vitro
      and as tumor xenografts in vivo. MYC sensitizes cells to DR5 in a p53-independent
      manner by upregulating DR5 cell surface levels and stimulating autocatalytic
      processing of procaspase-8. These results identify a novel mechanism by which MYC
      sensitizes cells to apoptosis and validate DR5 agonists as potential MYC
      selective cancer therapeutics.

PMID- 15144958
TI  - An epidemiological perspective on one tale of a two-tailed hypothesis.

PMID- 15144959
TI  - Long sleep and mortality: rationale for sleep restriction.
AB  - Epidemiologic studies have consistently shown that sleeping >8 h per night is
      associated with increased mortality. Indeed, the most recent American Cancer
      Society data of 1.1 million respondents showed that sleeping longer than 7.5 h
      was associated with approximately 5% of the total mortality of the sample. The
      excess mortality was found even after controlling for 32 potentially confounding
      risk factors. Although epidemiologic data cannot prove that long sleep duration
      causes mortality, there is sufficient evidence to warrant future testing of the
      hypothesis that mild sleep restriction would decrease mortality in long sleepers.
      Sleep restriction might resemble dietary restriction as a potential aid to
      survival. Sleep restriction has several potential benefits besides possible
      enhanced survival. Acute sleep restriction can have dramatic antidepressant
      effects. Also, chronic sleep restriction is perhaps the most effective treatment
      for primary insomnia. Conversely, spending excessive time in bed can elicit
      daytime lethargy and exacerbate sleep fragmentation, resulting in a vicious cycle
      of further time in bed and further sleep fragmentation. Sleep restriction may be
      most beneficial for older adults, who tend to spend excessive time in bed and
      have more sleep fragmentation compared with young adults.

PMID- 15144961
TI  - Self-report measures of insomnia in adults: rationales, choices, and needs.
AB  - Self-report measures continue to provide key information in the evaluation and
      treatment of insomnia. While knowledge development about insomnia continues to
      require multi-trait, multi-method studies, self-report measures remain central in
      most study designs. The available stock of insomnia-related questionnaires has a
      substantial heterogeneity in their formats, foci, scopes, and other attributes.
      While there may be benefits from using specially tailored questionnaires in
      particular circumstances, in other cases the information quality of a study will
      be downgraded by poor choice of questionnaires. To assist clinicians and
      investigators in selecting questionnaires wisely, the present paper reviews
      questionnaire criteria and attribute priorities for clinical trials, theory
      tests, observational studies, and aging studies concerning insomnia. An extensive
      table of currently available questionnaires is provided, and some needs for
      future questionnaire development are also identified.

PMID- 15144962
TI  - Impaired sleep and rhythms in persons with cancer.
AB  - This review includes research findings from sleep-related studies on specific
      types of cancers, on specific types of treatment protocols, and on persons with
      end-stage cancer regardless of treatment protocol. Since treatment protocols have
      evolved in the past decade, literature since 1990 is emphasized. We conclude that
      researchers should design studies that attend to prior sleep history, gender,
      type of cancer and treatment modalities, and the specific type of sleep problems
      experienced over the course of diagnosis, treatment, and recovery. More research
      is also needed to understand sleep problems in children with cancer and sleep
      problems in family caregivers. Research is also needed on effective
      pharmacological and non-pharmacological interventions. Daytime functioning,
      daytime sleepiness, and altered circadian rhythms should be considered salient
      outcomes in addition to severity of cancer-related fatigue. Clinicians should
      consider whether a patient's sleep problem has been chronic and unrelated to
      cancer, or precipitated by diagnosis and treatment. The specific type of sleep
      problem should be ascertained so that appropriate interventions can be
      prescribed. Appropriate interventions can include either pharmacological
      medication or behavioral strategies, and each has the potential to promote
      restorative sleep and thereby improve the patient's quality of life, daytime
      functioning, and well-being.

PMID- 15144963
TI  - Anesthesia and sleep.
AB  - Although both general anesthesia and naturally occurring sleep depress
      consciousness, distinct physiological differences exist between the two states.
      Recent lines of evidence have suggested that sleep and anesthesia may be more
      similar than previously realized. Localization studies of brain nuclei involved
      in sleep have indicated that such nuclei are important in anesthetic action.
      Additional observations that regional brain activity during anesthesia resembles
      that in the sleeping brain have raised the possibility that anesthesia may exert
      its effects by activating neuronal networks normally involved in sleep. In
      animals, behavioral interactions between sleep and anesthesia appear to support
      these mechanistic similarities. Rat studies demonstrate that sleep debt accrued
      during prolonged wakefulness dissipate during anesthesia. Moreover, anesthetic
      potency is subject both to circadian effects and to the degree of prior sleep
      deprivation. Such interactions may partly explain anesthetic variability among
      patients. Finally, sleep and anesthesia interact physiologically. Endogenous
      neuromodulators known to regulate sleep also alter anesthetic action, and
      anesthetics cause sleep with direct administration into brain nuclei known to
      regulate sleep. Together, these observations provide new research directions for
      understanding sleep regulation and generation, and suggest the possibility of new
      clinical therapies both for patients with sleep disturbances and for sleep
      deprived patients receiving anesthesia.

PMID- 15144964
TI  - Functional imaging of the sleeping brain: review of findings and implications for
      the study of insomnia.
AB  - Despite the growing literature indicating that insomnia is prevalent and a
      substantial risk factor for medical and psychiatric morbidity, the
      pathophysiology of both Primary and Secondary Insomnia is poorly understood.
      Multiple trait and state factors are thought to give rise to and/or moderate
      illness severity in insomnia, but 'hyperarousal' is widely believed to be the
      final common pathway of the disorder. To date, very little work has been
      undertaken using functional imaging to explore the CNS correlates, underpinnings,
      or consequences of hyperarousal as it occurs in Primary Insomnia. In fact, all
      but one of the extant studies have been of healthy good sleepers or subjects with
      Secondary Insomnia. In the present article, we: (1) review the studies that have
      been undertaken in good sleepers and in patients using functional neuroimaging
      methodologies, and (2) discuss how these data can inform a research agenda aimed
      at describing the neuropathophysiology of insomnia.

PMID- 15144966
TI  - Use of a novel array detector for the direct analysis of solid samples by laser
      ablation inductively coupled plasma sector-field mass spectrometry.
AB  - The use of laser ablation (LA) as a sample-introduction method for inductively
      coupled plasma mass spectrometry (ICP-MS) creates a powerful tool for trace
      elemental analysis. With this type of instrument, high analyte spatial resolution
      is possible in three dimensions with ng/g limits of detection and minimal sample
      consumption. Here, simultaneous detection is used to eliminate the correlated
      noise that plagues the ablation process. This benefit allows analyses to be
      performed with single laser pulses, resulting in improved depth resolution, even
      less sample consumption, and improved measurement precision. The new instrument
      includes an LA sample-introduction system coupled to an ICP ionization source and
      a Mattauch-Herzog mass spectrograph (MHMS) fitted with a novel array detector.
      With this instrument, absolute limits of detection are in the tens to hundreds of
      fg regime and isotope-ratio precision is better than 0.02% RSD with a one-hour
      integration period. Finally, depth-profile analysis has been performed with a
      depth resolution of 5 nm per ablation event.

PMID- 15144965
TI  - Advancing the neurobiology of insomnia, a commentary on: "Functional imaging of
      the sleeping brain" by Drummond et al.

PMID- 15144967
TI  - Intrinsic hydration of monopositive uranyl hydroxide, nitrate, and acetate
      cations.
AB  - The intrinsic hydration of three monopositive uranyl-anion complexes (UO(2)A)(+)
      (where A = acetate, nitrate, or hydroxide) was investigated using ion-trap mass
      spectrometry (IT-MS). The relative rates for the formation of the monohydrates
      [(UO(2)A)(H(2)O)](+), with respect to the anion, followed the trend: Acetate > or
      = nitrate >> hydroxide. This finding was rationalized in terms of the donation of
      electron density by the strongly basic OH(-) to the uranyl metal center, thereby
      reducing the Lewis acidity of U and its propensity to react with incoming
      nucleophiles, viz., H(2)O. An alternative explanation is that the more complex
      acetate and nitrate anions provide increased degrees of freedom that could
      accommodate excess energy from the hydration reaction. The monohydrates also
      reacted with water, forming dihydrates and then trihydrates. The rates for
      formation of the nitrate and acetate dihydrates [(UO(2)A)(H(2)O)(2)](+) were very
      similar to the rates for formation of the monohydrates; the presence of the first
      H(2)O ligand had no influence on the addition of the second. In contrast,
      formation of the [(UO(2)OH)(H(2)O)(2)](+) was nearly three times faster than the
      formation of the monohydrate.

PMID- 15144968
TI  - Optimized sample-processing time and peptide recovery for the mass spectrometric
      analysis of protein digests.
AB  - Proteomics requires an optimized level of sample-processing, including a minimal
      sample-processing time and an optimal peptide recovery from protein digests, in
      order to maximize the percentage sequence coverage and to improve the accuracy of
      protein identification. The conventional methods of protein characterization from
      one-dimensional or two-dimensional gels include the destaining of an excised gel
      piece, followed by an overnight in-gel enzyme digestion. The aims of this study
      were to determine whether: (1) stained gels can be used without any destaining
      for trypsin digestion and mass spectrometry (MS); (2) tryptic peptides can be
      recovered from a matrix-assisted laser desorption/ionization (MALDI) target plate
      for a subsequent analysis with liquid chromatography (LC) coupled to an
      electrospray ionization (ESI) quadrupole ion trap MS; and (3) an overnight in-gel
      digestion is necessary for protein characterization with MS. These three
      strategies would significantly improve sample throughput. Cerebrospinal fluid
      (CSF) was the model biological fluid used to develop these methods. CSF was
      desalted by gel filtration, and CSF proteins were separated by two-dimensional
      gel electrophoresis (2DGE). Proteins were visualized with either silver,
      Coomassie, or Stains-All (counterstained with silver). None of the gels was
      destained. Protein spots were in-gel trypsin digested, the tryptic peptides were
      purified with ZipTip, and the peptides were analyzed with MALDI and ESI MS. Some
      of the samples that were spotted onto a wax-coated MALDI target plate were
      recovered and analyzed with ESI MS. All three types of stained gels were
      compatible with MALDI and ESI MS without any destaining. In-gel trypsin digestion
      can be performed in only 10-60 min for protein characterization with MS, the
      sample can be recovered from the MALDI target plate for use in ESI MS, and there
      was a 90% reduction in sample-processing time from overnight to ca. 3 h.

PMID- 15144969
TI  - Chiral recognition of zinc(II) ion complexes composed of bicyclo[3.3.0] octane
      2,6-diol and s-naproxen probed by collisional-induced dissociation.
AB  - Chiral recognition of racemic bicyclo[3.3.0] octane-2,6-diol(B) was achieved in
      the gas phase using s-Naproxen(A) as reference, using the kinetics of competitive
      unimolecule dissociation of tetrameric zinc(II)-bound complexes by electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometer(ESI-FTMS).
      As undergoing a mild competitive collision-induced dissociation(CID) experiment
      with a constant pressure argon gas introduced by leak valve, the tetrameric
      cluster ion [A(2)B(2)Z(n)(II)-H](+) forms only two trimeric ions and R(chiral) is
      subsequently obtained in the kinetic method. Further studies obtained the
      difference of Gibbs free energy of [ABZ(n)(II)-H](+)(Delta Delta G(ABZn(II)
      H](+))) by dissociating [A(2)BZ(n)(II)-H](+), resulting two fragment ions
      [ABZ(n)(II)-H](+) and [A(2)Z(n)(II)-H](+), which can be established to a linear
      relationship between Delta Delta G([ABZn(II)-H](+)) and R(chiral)' basing on the
      kinetic method. The value of R(chiral)' suggested that Delta Delta G([ABZn(II)
      H](+)) could be regarded as zero. Meanwhile, dissociation of [AB(2)Z(n)(II)-H](+)
      generated only one daughter ion [ABZ(n)(II)-H](+) in a stable pressure. Thus, a
      linear relationship was established between the difference of Gibbs free energy
      of [AB(2)Z(n)(II)-H](+)(Delta Delta G([AB(2)Zn(II)-H](+))) and R(chiral)" if the
      Delta Delta G([ABZn(II)-H](+)) can be negligible. Because there is also a linear
      relationship of R(chiral) in the tetrameric ion [A(2)B(2)Z(n)(II)-H](+) and the
      Gibbs energy difference of trimeric cluster ion [A(2)BZ(n)(+)(II)-H](Delta Delta
      G([A(2)BZn(II)-H](+))) plus that of [AB(2)Z(n)(II)-H](+), Delta Delta
      G([A(2)BZ(n)(II)-H]+]) is easy to be calculated in the dissociation process of
      tetrameric ion. Stable of R(chiral), R(chiral)' and R(chiral)" under different
      pressures show T(eff) does not affect the chiral recognition of cluster ions in
      the condition selected. If an only-one-daughter-ion fragment process of
      [A(2)BZ(n)(II)-H](+) was existed, R(chiral)''' relating to this dissociation
      would be calculated just like R(chiral)" of [AB(2)Z(n)(II)-H](+) does. Conclusion
      was obtained that [A(2)BZ(n)(II)-H](+) makes more contribution to chiral
      recognition of tetrameric ion measured by kinetic method than [AB(2)Z(n)(II)
      H](+) does as R(chiral)''' and R(chiral)" were applied as index to evaluate the
      Gibbs free energy difference of these two trimeric cluster ions. Further
      discussion shows that steric interactions and pi-pi stacking interactions are the
      major factors responsible for the observed efficient chiral recognition in this
      system.

PMID- 15144971
TI  - Utilization of a multimembrane inlet and a cyclic sudden sampling introduction
      mode in membrane inlet mass spectrometry.
AB  - Sudden sampling introduction into a membrane inlet mass spectrometer (MIMS)
      considerably improves the selectivity of the membrane inlet and is therefore
      applicable even for compounds with low permeabilities through a silicone
      membrane. In this study the basics of cyclic non-steady-state sudden increase
      sample injection were studied using a three-membrane inlet and a portable sector
      double-focusing mass spectrometer. The operational parameters of the inlet system
      providing the most efficient enrichment of volatile organic compounds (VOCs) in
      air were defined. Simulation of the diffusion process following sudden sample
      introduction into the three-membrane inlet was also carried out. Experimental
      testing of the three-membrane inlet system with the cyclic sudden sample
      injection mode for benzene, toluene, styrene, and xylene in air was performed.
      The simulation and the experimental results demonstrated that, when this mode is
      used, the VOCs/nitrogen relative enrichment factor of samples introduced into the
      mass spectrometer equipped with a three-membrane inlet is increased by a factor
      of approximately 10(5) compared with a direct introduction method. This effect
      may be used to decrease detection limits of compounds obtained with mass
      spectrometry to decrease matrix flow through the inlet at the same detection
      limits.

PMID- 15144970
TI  - Development of an LC-MALDI method for the analysis of protein complexes.
AB  - In this study, a two-dimensional LC-MALDI-TOF/TOF method has been developed for
      analyzing protein complexes. In our hands, the method has proven to be an
      excellent strategy for the analysis of protein complexes isolated in pull-down
      experiments. This is in part because the preservation of the chromatographic
      separation on a MALDI target yields an "unlimited" amount of time to obtain MS/MS
      spectra, making it possible to probe more deeply into complex samples. A brief
      statistical analysis was performed on the data obtained from the LC-MALDI-TOF/TOF
      system in order to better understand peptide fragmentation patterns under high
      energy collision conditions. These statistical analyses provided some insight
      into how to evaluate the quality and accuracy of the database search results
      derived from the TOF/TOF-based analysis. The potential of the method was
      demonstrated by the successful identification of all the known penicillin-binding
      proteins in E. coli isolated using a drug-based pull-down with ampicillin as the
      bait. The performance of the LC-MALDI-TOF/TOF system was compared with that of an
      equivalent 2D LC-ESI-MS/MS approach, in the analysis of a protein bait-based pull
      down. Regardless of the number of peptides identified in the ESI versus MALDI
      approach, the two approaches were found to be complementary. When the data is
      merged at the peptide level, the combined result gives higher Mascot scores and
      an overall higher confidence in protein identification than with either approach
      alone.

PMID- 15144972
TI  - Mass spectrometric detection of affinity purified crosslinked peptides.
AB  - Chemical crosslinking of proteins combined with mass spectrometric analysis of
      the tryptic digest of the products shows considerable promise as a tool for
      interrogating structure and geometry of proteins and protein complexes. An
      impediment to the use of this tool has been the difficulty of distinguishing
      crosslinked peptide pairs from non-crosslinked peptides, and from the products of
      side reactions. We describe the use of a commercially available biotinylated
      crosslinking reagent, sulfo-SBED, that allows affinity-based enrichment of
      crosslinked species. An intramolecular crosslink is prepared using the peptide
      neurotensin as a model system. Matrix-assisted laser desorption/ionization time
      of-flight (MALDI-TOF) mass spectra show the predicted crosslinking product, as
      well as several side products. Finally, we describe the optimized enrichment of
      biotinylated species, and reduction of non-specific binding, for a batch-mode
      affinity separation based on immobilized monomeric avidin.

PMID- 15144973
TI  - Isomeric discrimination of arginine-containing dipeptides using electrospray
      ionization-ion trap mass spectrometry and the kinetic method.
AB  - The Kinetic Method (KM), applied commonly for thermochemical determinations, is
      used here for sterically-controlled isomeric determination of N- versus C
      terminal Arg-containing dipeptide isomers (ArgX versus XArg; where X = His, Leu,
      Lys, Pro, Ser, Phe, and Tyr). The KM is offered as an alternate approach to
      direct collision-induced dissociation (CID) procedures. Through formation,
      isolation, and dissociation of a sterically-encumbered, metal-centered complex
      with electrospray ionization ion trap mass spectrometry technology, reference
      dipeptide molecules are screened to quantitatively differentiate a mixture of
      isomers based on their arrangement about the metal center. Arg-containing
      dipeptide molecules are chosen because of their contribution in a wide array of
      protein and peptide functions. Additionally, problems cited previously for
      evaluation of systems containing Arg residues (due to the incorporation of the
      guanidinium moiety) by the KM are addressed. The method is shown to be successful
      for highlighting favorable reference analytes (e.g., ArgPhe, ArgLeu, ProArg,
      PheArg, among others) for exceptional discrimination (R(iso) > 2.0) of the
      majority of N- and C-terminal Arg-containing peptides tested.

PMID- 15144974
TI  - Toward the prediction of the activity of antioxidants: experimental and
      theoretical study of the gas-phase acidities of flavonoids.
AB  - The relative gas-phase acidities were determined for eight flavonoids, applying
      the kinetic method, by means of electrospray-ion trap mass spectrometry. The
      experimental acidity order, myricetin > luteolin > quercetin > (+/-)-taxifolin >
      kaempferol > apigenin > (+)-catechin > (+/-)-naringenin shows good agreement with
      the order obtained by theoretical calculations at the B3LYP/6-311 +
      G(2d,2p)//HF/6-31G(d) level. Moreover, these calculations provide the gas-phase
      acidities of the different OH groups for each flavonoid. The calculated acidity
      values (Delta(ac)H), corresponding to the most favorable deprotonation, cover a
      narrow range, 314.8-330.1 kcal/mol, but the experimental method is sensitive
      enough to differentiate the acidity of the various flavonoids. For all the
      flavones and the flavanol, catechin, the 4'-hydroxyl group is the most favored
      deprotonation site whereas for the flavanones studied, taxifolin and naringenin,
      the most acidic site is the 7-hydroxyl group. On the other hand, the 5-hydroxyl,
      in flavones and naringenin, and the 3-hydroxyl, in taxifolin and catechin, are
      always the less acidic positions. The acidity pattern observed for this family of
      compounds mainly depends on the following structural features: The ortho-catechol
      group, the 2,3 double bond and the 4-keto group.

PMID- 15144975
TI  - Electrospray/mass spectrometric identification and analysis of 4-hydroxy-2
      alkylquinolines (HAQs) produced by Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa produces a large array of 4
      hydroxy-2-alkylquinolines (HAQs). These compounds were analyzed by LC/MS, using
      positive electrospray ionization, in the culture supernatant of strain PA14.
      Fifty-six HAQs and related compounds were detected and their [M + H](+) ions were
      further analyzed by collision induced dissociation (CID). These HAQs were grouped
      into five different series based on the presence of an hydrogen or hydroxyl group
      at the 3 position, an N-oxide group in place of the quinoline nitrogen, and an
      unsaturation on their alkyl side chain. Two new analogs of 3,4-dihydroxy-2
      heptylquinoline, the Pseudomonas quinolone signal (PQS), were found with an alkyl
      chain longer by one and two methylene groups. Moreover, two additional series of
      compounds were identified in which a saturated or unsaturated alkyl side chain is
      located at the 3 position along with an hydroxyl group at the 3 position and a
      ketone at the 2 position. No HAQ N-oxides, nor any compounds from the latter two
      series, were detected in a pqsL mutant derivative of PA14, indicating that this
      gene is involved in the biosynthesis of these compounds. This work demonstrates
      the large repertoire of HAQ and HAQ-related compounds produced by P. aeruginosa,
      and provides insight into N-oxides biosynthesis and confirm the hypothesis that N
      oxides are the precursors of compounds from Series 6 and 7.

PMID- 15144977
TI  - Cationization of simple organic molecules by singly-charged Ag3+ cluster ions in
      matrix-assisted laser desorption/ionization mass spectrometry: metal cluster
      molecule interactions.
AB  - It was found earlier that under matrix-assisted laser desorption/ionization
      (MALDI) conditions several organic compounds which produce adduct with silver
      ions, are also capable of forming adducts with Ag(3)(+) cluster ions under
      appropriate conditions. The Ag(3)(+) cluster ion can be in situ generated under
      the MALDI analysis conditions from silver trifluoroacetate cationization agent in
      the presence of organic MALDI matrices. In this article the fragmentation of a
      commercial plasticizer, a peracetylated isoflavone glycoside and a
      pyrazolylphenyl disulfide derivative cationized with silver ions and Ag(3)(+)
      cluster ions are compared. It was observed that the complexes of Ag(3)(+) are
      less fragmented than the corresponding adduct ions with Ag(+). The presumable
      fragmentation channel of [M + Ag(3)(+)] is the elimination of Ag(2) units from
      these complexes. No significant dissociation of [M + Ag(3)(+)], into M and
      Ag(3)(+) takes place, indicating a tight connection between the corresponding
      molecule and Ag(3)(+) cluster ion. However, with a compound carrying very labile
      groups, such as the pyrazolylphenyl disulfide derivative, intramolecular
      cleavages can occur prior to significant dissociation of the Ag(3)(+) cluster
      ion.

PMID- 15144976
TI  - Ion mobility-mass spectrometry applied to cyclic peptide analysis: conformational
      preferences of gramicidin S and linear analogs in the gas phase.
AB  - In this paper, we present an investigation of the gas-phase structural
      differences between cyclic and linear peptide ions by matrix-assisted laser
      desorption ionization-ion mobility-mass spectrometry. Specifically, data is shown
      for gramicidin S (cyclo-VOLFPVOLFP where phenylalanines are D rather than L-type
      amino acids and the O designates the non-standard amino acid ornithine) and five
      linear gramicidin S analogues. Results are interpreted as evidence for a beta
      sheet (or beta-hairpin) conformational preference in both linear-protonated and
      sodiated-cyclic gramicidin S gas-phase peptides, and a preference for the
      protonated-cyclic peptide to adopt a collapsed, random coil-type conformation. A
      comparison with solution-phase circular dichroism measurements is performed, and
      structures similar to those observed in the gas phase appear to be favored in low
      dielectric solvents such as 2,2,2-triflouroethanol. The utility of ion mobility
      mass spectrometry (IM-MS) as a means of rapidly distinguishing between linear and
      cyclic peptide forms in also discussed.

PMID- 15144978
TI  - High throughput screening of library compounds against an oligonucleotide
      substructure of an RNA target.
AB  - Approximately 300,000 compounds from selected libraries were screened against a
      subdomain of a hepatitis C viral (HCV) RNA using a high throughput flow injection
      mass spectrometry (FIA-MS) method with automated data storage and analysis.
      Samples contained 2 microM RNA target and 10 microM of each of up to ten ligands.
      Preliminary studies to optimize operational parameters used the binding of
      aminoglycosides to the A44 subdomain of bacterial RNA. Binding (confirmed by
      titration) and sensitivity were maximized within the constraints of the library
      and throughput. The mobile phase of 5 mM ammonium acetate in 50% isopropanol
      maintained the noncovalent complexes and provided good detection by electrospray
      mass spectrometry. Additionally, this composition maximized general solubility of
      the various classes of compounds including the oligonucleotide and organic
      library molecules. Cation adduction was insignificant in this screen although
      some solute and target dependent acetate adduction was observed. The ion trap
      mass spectrometer provided sufficient mass resolution to identify complexes of
      RNA with known components of the library. Converted mass spectral data (netCDF)
      were subjected to two types of statistical evaluation based on binding. The first
      algorithm identified noncovalent complexes that correlated with the molecular
      weights of the injected compounds. The second yielded the largest peak in the
      noncovalent complex region of the spectrum; this spectrum may or may not
      correlate with expected well components. Sixty-three compounds were confirmed to
      bind by more stringent secondary testing. Titrations, which were carried out with
      selected binding compounds, yielded a range of dissociation constants. Biological
      activity was observed for eleven confirmed binders.

PMID- 15144979
TI  - Analysis of polyaniline oligomers by laser desorption ionization and solventless
      MALDI.
AB  - While direct laser desorption ionization of soluble polyaniline dried onto metal
      sample plates results in mass spectra that are similar to previously shown
      electrospray ionization data of similar samples, laser desorption of
      unsolubilized solid polyaniline results in major fragmentation of the phenyl
      rings. Solventless MALDI, a recently developed technique for insoluble or
      slightly soluble species, involves the use of only solid analyte and matrix
      during sample preparation. Solventless MALDI of solid polyaniline results in mass
      spectra that are similar to the direct laser desorption ionization spectra of the
      soluble oligomers with some larger molecular weight oligomers also being
      detected. Based on the matrix used, different series of polyaniline with
      dissimilar end groups are detected. The matrix also affects the percentages of
      benzenoid and quinoid units in the oligomers. Thus, solventless MALDI appears to
      be a promising new technique for the mass spectrometric analysis of low
      solubility, but industrially important, polyanilines.

PMID- 15144981
TI  - SILVER helps assign peptides to tandem mass spectra using intensity-based
      scoring.
AB  - Tandem mass spectrometry is commonly used to identify peptides (and thereby
      proteins) that are present in complex mixtures. Peptide identification from
      tandem mass spectra is partially automated, but still requires human curation to
      resolve "borderline" peptide-spectrum matches (PSMs). SILVER is web-based
      software that assists manual curation of tandem mass spectra, using a recently
      developed intensity-based machine-learning approach to scoring PSMs, Elias et al.
      In this method, a large training set of peptide, fragment, and peak-intensity
      properties for both matched and mismatched PSMs was used to develop a score
      measuring consistency between each predicted fragment ion of a candidate peptide
      and its corresponding observed spectral peak intensity. The SILVER interface
      provides a visual representation of match quality between each candidate fragment
      ion and the observed spectrum, thereby expediting manual curation of tandem mass
      spectra. SILVER is available online at
      http://llama.med.harvard.edu/Software.html.

PMID- 15144980
TI  - Toward understanding the ionization of biomarkers from micrometer particles by
      bio-aerosol mass spectrometry.
AB  - The appearance of informative signals in the mass spectra of laser-ablated bio
      aerosol particles depends on the effective ionization probabilities (EIP) of
      individual components during the laser ionization process. This study
      investigates how bio-aerosol chemical composition governs the EIP values of
      specific components and the overall features of the spectra from the bio-aerosol
      mass spectrometry (BAMS). EIP values were determined for a series of amino acid,
      dipicolinic acid, and peptide aerosol particles to determine what chemical
      features aid in ionization. The spectra of individual amino acids and dipicolinic
      acid, as well as mixtures, were examined for extent of fragmentation and the
      presence of molecular ion dimers, which are indicative of ionization conditions.
      Standard mixtures yielded information with respect to the significance of
      secondary ion plume reactions on observed spectra. A greater understanding of how
      these parameters affect EIP and spectra characteristics of bio-aerosols will aid
      in the intelligent selection of viable future biomarkers for the identification
      of bio-terrorism agents.

PMID- 15144982
TI  - Quantitative determination of the selectivities of five different phenyl radicals
      in hydrogen atom abstraction from ethanol.
AB  - An experimental method is described for obtaining quantitative selectivity
      information for H-atom abstraction by organic radicals from different sites of a
      substrate in the gas phase. The method is used to determine the selectivities of
      five different phenyl radicals toward the three different types of hydrogen atoms
      in ethanol. This experimental method involves studying the reactivities and
      selectivities of derivatives of the radicals that contain a chemically inert,
      charged group (distonic ions), which allows them to be manipulated in a Fourier
      transform ion cyclotron resonance (FT-ICR) mass spectrometer.

PMID- 15144983
TI  - GC/MS analysis of thermally degraded neuromelanin from the human substantia
      nigra.
AB  - Neuromelanin (NM) is a complex polymer pigment found in catecholaminergic neurons
      of the human brain. The structure, formation pathway, and physiological function
      of NM have not yet been clarified, but interest in this polymer has been sparked
      by the suggestion that NM is involved in cell death in Parkinson's disease. In
      the current study, pyrolysis-gas chromatography/mass spectrometry analysis was
      applied for structural investigation of NM isolated from the human substantia
      nigra, using synthetic eumelanin and pheomelanin-type pigments as reference
      materials. None of the heterocyclic, sulfur-containing compounds being
      characteristic thermal degradation products of cysteinyldopamine-derived units of
      synthetic pheomelanin standard was detected in the pyrolysates of natural NM. The
      results suggest that nigral pigment isolated from normal brain tissue does not
      contain benzothiazine-type monomer units. Pyrolytic experiments in the presence
      of a derivatizing agent allowed identification of high levels of saturated and
      monounsaturated straight-chain C14-C18 fatty acids and led to the conclusion that
      a part of a lipid component is chemically bound to the NM macromolecule. The
      nigral pigment was also shown to be tightly associated with an isoprenoid-type
      compound.

PMID- 15144984
TI  - Generation and reactions of anionic sigma-adducts of 1,3-dinitrobenzene and 1,3,5
      trinitrobenzene with carbanions in a gas phase, using an electrospray ion source
      as the chemical reactor.
AB  - Di- and trinitrophenide anions generated by decarboxylation of the anions of 2,4
      , 3,5-, and 2,6-dinitrobenzoic acids and 1,3,5-trinitrobenzoic acid in the medium
      pressure region of an electrospray ion source react locally with various C-H
      acids delivered in the form of vapors mixed with the curtain gas, yielding
      anionic sigma-adducts. Positive results were obtained for aliphatic aldehydes,
      ketones, esters and nitriles. All three dinitrobenzoic acids bearing NO(2) groups
      in the meta position to each other gave the same sigma-adducts which can be
      rationalized by a reaction sequence including proton transfer from the C-H acid
      to the nitrophenide anion and subsequent formation of the sigma-adduct by the
      reaction of 1,3-dinitrobenzene with the carbanion within the ion-molecule
      complex. It was found that such a reaction is possible only for C-H acids with a
      gas-phase acidity lying within a narrow, strictly defined range whose location on
      the acidity scale depends on the acidity of the nitroarene. The sigma-adduct
      formed in the reaction of the 2,4-dinitrophenide anion with CH(2)Cl(2) undergoes
      rapid HCl elimination yielding an anion with the same composition as that
      produced by the Vicarious Nucleophilic Substitution of hydrogen reaction but with
      a different structure.

PMID- 15144985
TI  - Infrared laser post-ionization of large biomolecules from an IR-MALD(I) plume.
AB  - A two-infrared laser desorption/ionization method is described. A first laser,
      which was either an Er:YAG laser or an optical parametric oscillator (OPO),
      served for ablation/vaporization of small volumes of analyte/matrix sample at
      fluences below the ion detection threshold for direct matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). A second IR-laser, whose beam
      intersected the expanding ablation plume at a variable distance and time delay,
      was used to generate biomolecular ions out of the matrix-assisted laser
      desorption (MALD) plume. Either one of the two above lasers or an Er:YSGG laser
      was used for post-ionization. Glycerol was used as IR-MALDI matrix, and mass
      spectra of peptides, proteins, as well as nucleic acids, some of which in excess
      of 10(5) u in molecular weight, were recorded with a time-of-flight mass
      spectrometer. A mass spectrum of cytochrome c from a water ice matrix is also
      presented. The MALD plume expansion was investigated by varying the position of
      the post-ionization laser beam above the glycerol sample surface and its delay
      time relative to the desorption laser. Comparison between the OPO (pulse
      duration, tau(L) = 6 ns) and the Er:YAG laser (tau(L) approximately 120 ns) as
      primary excitation laser demonstrates a significant effect of the laser pulse
      duration on the MALD process.

PMID- 15144987
TI  - Aristotle scores in congenital heart surgery.

PMID- 15144989
TI  - Midterm results of the Ross procedure.
AB  - OBJECTIVE: The lack of durable bioprosthetic valves and the inherent risks
      associated with anticoagulation for mechanical valves have led to the continued
      use of the Ross procedure, particularly in the pediatric population. METHODS: We
      have reviewed our mid-term results retrospectively, following the Ross operation
      in both pediatric and adult groups. RESULTS: Over a 11-year period from August
      1991 to August 2002, 60 patients underwent the Ross procedure. The median age was
      15 years (6-804 months), of which 63% were males and 55% were under the age of 20
      years. The main indications were: aortic stenosis in 47 patients; aortic
      insufficiency in 6 patients; and mixed aortic valve disease in 28 patients.
      Fifteen patients had previously undergone balloon dilatation of the aortic valve,
      4 had open valvotomy and 3 had both valvuloplasty procedures. The pulmonary
      autograft was implanted as a sub-coronary implant until 1995 (30%) after which
      time it was implanted using a partial inclusion cylinder technique (70%). There
      have been no deaths reported in this series. Over a median follow-up period of 59
      months (2-122 months), there have been four re-operations for repair of autograft
      leak, and 2 adult patients have had autograft replacements. CONCLUSIONS: Despite
      the increased technical complexity, the Ross procedure can be performed safely in
      both paediatric and adult populations with satisfactory medium term results.

PMID- 15144988
TI  - The Aristotle score: a complexity-adjusted method to evaluate surgical results.
AB  - OBJECTIVES: Quality control is difficult to achieve in Congenital Heart Surgery
      (CHS) because of the diversity of the procedures. It is particularly needed,
      considering the potential adverse outcomes associated with complex cases. The aim
      of this project was to develop a new method based on the complexity of the
      procedures. METHODS: The Aristotle project, involving a panel of expert surgeons,
      started in 1999 and included 50 pediatric surgeons from 23 countries,
      representing the EACTS, STS, ECHSA and CHSS. The complexity was based on the
      procedures as defined by the STS/EACTS International Nomenclature and was
      undertaken in two steps: the first step was establishing the Basic Score, which
      adjusts only the complexity of the procedures. It is based on three factors: the
      potential for mortality, the potential for morbidity and the anticipated
      technical difficulty. A questionnaire was completed by the 50 centers. The second
      step was the development of the Comprehensive Aristotle Score, which further
      adjusts the complexity according to the specific patient characteristics. It
      includes two categories of complexity factors, the procedure dependent and
      independent factors. After considering the relationship between complexity and
      performance, the Aristotle Committee is proposing that: Performance = Complexity
      x Outcome. RESULTS: The Aristotle score, allows precise scoring of the complexity
      for 145 CHS procedures. One interesting notion coming out of this study is that
      complexity is a constant value for a given patient regardless of the center where
      he is operated. The Aristotle complexity score was further applied to 26 centers
      reporting to the EACTS congenital database. A new display of centers is presented
      based on the comparison of hospital survival to complexity and to our proposed
      definition of performance. CONCLUSION: A complexity-adjusted method named the
      Aristotle Score, based on the complexity of the surgical procedures has been
      developed by an international group of experts. The Aristotle score,
      electronically available, was introduced in the EACTS and STS databases. A
      validation process evaluating its predictive value is being developed.

PMID- 15144990
TI  - Life insurance and mortgage application in adults with congenital heart disease.
AB  - OBJECTIVE: To compare the outcome of life insurance and mortgage applications of
      adults with congenital heart disease (CHD) with controls and at different
      severities of CHD. METHODS: Two hundred and ninety-nine adult CHD patients
      underwent a questionnaire-based interview by a trained nurse. They were asked to
      give an identical questionnaire to a friend to act as a control. One hundred and
      seventy-seven controls replied. CHD patients were classified into three
      categories based on severity. Comparisons were made between matched controls and
      between different severities of CHD. RESULTS: Similar proportions of the CHD
      group (59%) had applied for life insurance as matched controls (56%). Compared to
      controls, significantly more of the adults with CHD who had applied for life
      insurance have been refused (34 vs 4%, P < 0.0001) or asked to pay extra (37 vs
      6%, P = 0.0002). Mortgage application rate was also similar in both groups with
      more of the CHD patients refused than matched controls (20 vs 3%, P = 0.0004).
      These differences in both life insurance and mortgage remain significant when the
      cases and controls are matched by employment status and NYHA functional class.
      There was no significant difference in life insurance and mortgage application
      outcome between the groups of mild, significant and complex CHD. CONCLUSIONS:
      Adults with CHD are significantly more likely to have difficulty obtaining life
      insurance or a mortgage than controls. Refusal rates appear to be independent of
      the severity of CHD. This suggests that the label of CHD may have a negative
      impact despite the lesion being minor and that the outcome of an individual
      application is difficult to predict based on the severity of the CHD. The
      increasing numbers of adults with CHD suggest that this problem is likely to
      increase and needs to be addressed as it can have a major impact on the patient's
      quality of life.

PMID- 15144991
TI  - Effects of ultrafiltration and peritoneal dialysis on proinflammatory cytokines
      during cardiopulmonary bypass surgery in newborns and infants.
AB  - OBJECTIVES: To assess the impact of balanced ultrafiltration and peritoneal
      dialysis (PD) on plasma and urinary cytokines and renal dysfunction after
      cardiopulmonary bypass (CPB) surgery in newborns and infants. METHODS: Twenty
      three newborns and infants weighing less than 7 kg and scheduled for operation on
      congenital malformation were enrolled in this descriptive open clinical study.
      All patients received conventional ultrafiltration in the CPB rewarming period.
      Eleven newborns underwent Tenckhoff-catheter implantation in the operation
      theatre as a routine institutional procedure and received PD after admission to
      the ICU (the PD [+] group). No PD was used in another 12 patients (the PD [-]
      group). Interleukins (IL) 6 and 8 were measured four times pre- and post
      operatively. Kidney function was assessed by creatinine clearances and urine
      protein and enzyme analyses. RESULTS: All patients had an uneventful clinical
      course. Age (10+/-2 days, PD [+] vs. 96+/-19 days, PD [-]), CPB duration (215+/
      23 vs. 143+/-20 min), and degree of hypothermia (26+/-1.3 vs. 31+/-0.1 degrees C)
      differed significantly between the groups. Age, CPB duration and ultrafiltration
      influenced post-operative IL-levels in an analysis of variance. While there were
      few differences immediately after the end of ultrafiltration, post-operative
      levels of IL-6 and IL-8 were higher and more sustained in the newborns (PD [+])
      than in the older infants (PD [-]). The median amount of IL-6 and IL-8 removed by
      ultrafiltration came to 28 and 59% compared to the amount of IL-6 and IL-8
      remaining in the blood at the end of CPB. IL-clearance by ultrafiltration was
      more than 1000-fold and by PD more than 100-fold as effective as IL-clearance by
      the kidney. While the kidneys showed an unselective mixed glomerular and tubular
      pattern of injury, during CPB higher serum IL-concentrations correlated with
      lower urinary IL-clearances in both study groups. CONCLUSIONS: Ultrafiltration
      and PD are highly effective in removing proinflammatory cytokines. Impaired
      kidney function was associated with proinflammatory IL-serum concentrations.
      Thus, we raise the hypothesis that glomerular-filtered proinflammatory ILs damage
      the proximal tubular cells of the kidney in newborns and infants, thus
      contributing to post-operative renal dysfunction. Conversely, we conclude that
      removing proinflammatory ILs by ultrafiltration and PD acts renoprotectively. A
      future prospective randomised study could demonstrate whether this can indeed
      improve clinical outcome.

PMID- 15144992
TI  - Changes in type B natriuretic peptide (BNP) concentrations during cardiac valve
      replacement.
AB  - OBJECTIVE: The aim of our study was to investigate the ability of BNP levels to
      reveal the immediate post-surgery cardiac function improvement. We measured the
      perioperative variations in BNP concentrations in patients scheduled for cardiac
      surgery with cardiopulmonary bypass (CPB), chronic mitral regurgitation, valvular
      aortic stenosis, or myocardial ischaemia. METHODS: Three groups were included:
      patients with coronary artery bypass graft (CABG, group I, n = 14), aortic (AVR,
      group II, n = 14) or mitral (MVR, group III, n = 7) valve replacement. BNP assay
      was performed at the induction of anesthesia, immediately after the CPB, at the
      arrival in the intensive care unit, 4 h, 8 h and 12 h after the arrival in ICU.
      RESULTS AND CONCLUSION: The occurring variation in BNP levels after the operation
      is an increase whatever the corrective surgery, underlying the relative lack of
      specificity of BNP with regard to the cardiac pathology. Besides iatrogenic
      cardioplegia one can supposes that cardiac surgery involves other major stimuli
      such as anesthesia, sternotomia, hemodynamics, post-operative that could
      influence in a non specific way BNP levels.

PMID- 15144993
TI  - Introduction of a flexible polymeric heart valve prosthesis with special design
      for aortic position.
AB  - OBJECTIVE: Current prosthetic heart valves necessitate permanent anticoagulation
      or have limited durability and impaired hemodynamic performance compared to
      natural valves. Recently a polymeric valve prostheses with special design for
      mitral position demonstrated excellent in vitro and in vivo results with improved
      durability and no need for permanent anticoagulation. In this study, a respective
      flexible polymeric aortic valve is presented and in vitro and in vivo results are
      reported. METHODS: The aortic prosthesis (ADIAM lifescience AG, Erkelenz,
      Germany) is entirely made of polycarbonaturethane. The tri-leaflet flexible
      prosthesis mimicks the natural aortic valve and has a diminished pressure loss
      and reduced stress and strain peaks at the commissures. The valve underwent long
      term in vitro testing and in vivo-testing in a growing calve animal model (20
      weeks, 7 aortic valves) and was compared to two different commercial
      bioprostheses. RESULTS: The polymeric aortic heart valve substitute demonstrated
      excellent in vitro and in vivo hemodynamics. Five/seven animals with aortic PCU
      prostheses had an excellent clinical long-term course. The explanted valves
      showed a variable degree of calcification. Two of the seven animals died at 27
      and 77 days due to pannus overgrowth causing severe LVOTO without degeneration of
      the valve itself. Both animals with commercial bioprostheses had to be sacrificed
      because of congestive heart failure related to structural degeneration of the
      bioprosthesis after 10 and 30 days of implantation. There was no increased
      thrombogenity of the PCU valves compared to bioprostheses. CONCLUSION: The new
      flexible polymeric aortic valve prosthesis is superior to current bioprostheses
      in animal testing.

PMID- 15144994
TI  - Leaflet arrest in St Jude Medical and CarboMedics valves: an experimental study.
AB  - OBJECTIVE: Two patients who suffered acute failure of their St Jude Medical
      Masters aortic valve prostheses due to leaflet arrest that were unrelated to
      suture material are presented. It was hypothesized that the valves failed because
      force applied to bear upon the valve annulus caused the hinge mechanism to become
      restricted or to arrest. METHODS: A study was designed to measure the force that
      would cause leaflet arrest in three sizes of St Jude Medical Masters valves and
      CarboMedics mechanical valves. A specially manufactured pushrod device was used
      to apply a variable force to the sewing cuff, low annulus level, or to the pivot
      guards of all the valves. RESULTS: For every valve size tested, the St Jude
      Medical Masters valves required significantly less force applied than did the
      CarboMedics valves to cause one or both leaflets to arrest (P < 0.0004).
      CONCLUSIONS: A force applied on the valve ring of mechanical valves can cause
      leaflet arrest. The force required to arrest the leaflets is within an order of
      magnitude of that measured in other in vivo animal studies. We conclude that
      force on the valve rings in patients after aortic valve surgery could cause
      leaflet malfunction and even arrest in some patients.

PMID- 15144995
TI  - HeartMate VE LVAS design enhancements and its impact on device reliability.
AB  - OBJECTIVE: The HeartMate VE left ventricular assist system (LVAS) has supported
      more than 2300 patients and has been shown to be effective for bridge to cardiac
      transplantation and has demonstrated improved outcomes in survival as a
      destination therapy. Improvements in device durability are needed as bridge to
      transplant times increase and as we move into the era of LVAD as destination
      therapy. The purpose of this study is to determine if design enhancements to the
      HeartMate LVAS have improved device reliability and durability. METHODS: A
      retrospective analysis of serious mechanical failures was performed in 1865
      devices (1458 VE, 407 XVE). The analysis of data included devices used to support
      patients from September 1998 for bridge to transplantation and destination
      therapy. Serious mechanical failures were defined as inflow valve dysfunction,
      percutaneous lead breaks, diaphragm fractures or punctures, bearing failures,
      outflow graft erosion and pump disconnects. RESULTS: Median device duration for
      the VE was 97 days (max 1206 days), and 85 days (max 517 days) for the XVE. A
      total of 134 serious mechanical failures occurred and included inflow valve
      dysfunction (5.3% VE, 2.4% XVE) (P = 0.853) percutaneous lead breaks (1.9% VE, 0%
      XVE) (P < 0.001) diaphragm fractures (0.1% VE, 0% XVE) (P = 0.134) outflow graft
      erosion (0.2% VE, 0% XVE) (P = 0.1096), pump disconnects (0.1% VE, 0% XVE) (P =
      0.1336) and bearing failures (0.6% VE, 0.2% XVE) (P = 0.5538). Of the XVEs 97%
      were free of serious mechanical failures at 6 months and 82% at 1 year compared
      to 92 and 73% for the VE, respectively. The 6-month difference between the
      devices was statistically significant (P = 0.0063) and there was no statistically
      significant difference at 1 year (P = 0.1492). CONCLUSIONS: Preliminary
      experience with the HeartMate XVE LVAS demonstrated a significant reduction in
      percutaneous lead breaks. Early trends indicate positive impact of recent design
      modifications on XVE performance. These design modifications may improve device
      durability and reliability, which is crucial as we enter the era of LVADs as an
      alternative to medical therapy.

PMID- 15144996
TI  - First experiences with a novel magnetically suspended axial flow left ventricular
      assist device.
AB  - Axial flow pumps have gained increased acceptance since their first clinical use
      in 1998. The present report summarizes the clinical experience with patients
      treated for severe cardiogenic shock for the first time with a newly developed
      axial flow pump with magnetically levitated bearings. MATERIAL AND METHODS: The
      axial flow pump Incor was implanted in 24 patients between June 2002 and June
      2003. All except one patient were men. In 16 patients dilative cardiomyopathy, in
      seven ischemic and in one restrictive cardiomypathy had been diagnosed. All
      patients presented with catecholamine-dependent end-stage heart failure, seven of
      them were on an artificial ventilator and three were dependent on intraaortic
      balloon pump support. All patients suffered from organ dysfunction resulting from
      low cardiac output. RESULTS: There were no perioperative deaths. The 30-day
      mortality rate was 8% (n = 2); 79% ( n = 19) of patients reached a condition to
      be discharged home. The cumulative time on the device is 6.9 years; the longest
      individual time up to July 1, 2003 is 12.6 months. There were no structural
      defects or failures of the system. In one case the controller had to be exchanged
      because of intermittent malfunction. Cardiac output ranged between 4 and 6 l in
      all instances and there were no cases of infection of the drive-line or the
      system. Hemolysis was present initially but was not detectable in the later
      course. There were three instances of transient ischemic attacks. Two patients
      developed late cardiac tamponade with re-opening of the chest after 9 and 14
      days. In one patient persistent gastrointestinal bleeding required re
      hospitalization and transfusion therapy. Two patients were weaned from the device
      after 6 and 7 months of support, respectively. CONCLUSION: The preliminary
      clinical experience with Incor is promising. The flow is sufficient for recovery
      from multiorgan failure and the pump allows long-term hemolysis-free support. The
      concept of magnetically levitated bearings has proven to be durable and reliable.
      In the case that the heart may recover through unloading, weaning from the pump
      is possible.

PMID- 15144997
TI  - Implantable left ventricular assist device for treatment of pulmonary
      hypertension in candidates for orthotopic heart transplantation-a preliminary
      study.
AB  - OBJECTIVES: Elevated pulmonary vascular resistance (PVR) unresponsive to
      pharmacological intervention is a major limitation in heart transplantation
      (HTX). The post-operative course of these patients is associated with an
      increased risk of life-threatening right heart failure. We evaluated the
      efficiency of an implantable left ventricular assist device (LVAD) to decrease
      PVR by unloading the left ventricle and to lower the risk of later orthotopic
      HTX. METHODS: Six patients with end-stage heart failure (NYHA class IV) and
      'fixed' pulmonary hypertension (PVR 5.7+/-0.7, range 4.4-6.5 Wood units) were
      analyzed. Despite maximal pharmacological intervention at initial evaluation
      (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to
      under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a
      Novacor, and one patient a Jarvik 2000. RESULTS: All patients survived the LVAD
      implantation, four patients could be discharged from hospital. Cardiac index and
      pulmonary artery pressure values returned to normal during the early post
      operative phase. After a mean support time of 191+/-86 days PVR had fallen to
      2.0+/-1.2 (range 0.8-3.6) Wood units. All patients could be bridged to
      transplantation, one patient died 3 months after transplant, five patients are
      still alive after a mean follow-up of 16.2+/-10.5 months. CONCLUSIONS: Mechanical
      support using an implantable LVAD is a very efficient approach with an acceptable
      risk to treat severe pulmonary hypertension in end-stage heart failure patients
      before HTX. Adequate reduction of PVR can be expected within 3-6 months.
      Subsequent HTX is associated with a good outcome.

PMID- 15144998
TI  - Evaluation of serial haemodynamic changes during coronary artery anastomoses in
      patients undergoing off-pump coronary artery bypass graft surgery: initial
      experiences using two deep pericardial stay sutures and octopus tissue
      stabilizer.
AB  - OBJECTIVE: This study was designed to evaluate the serial haemodynamic changes
      during coronary artery anastomoses using two deep pericardial stay sutures and
      octopus tissue stabilizer in patients undergoing initial experiences of off-pump
      coronary artery bypass graft surgery (OPCAB) using continuous cardiac output and
      mixed venous oxygen saturation (SvO(2)) monitoring. METHODS: With IRB approval,
      thirty patients undergoing OPCAB were studied. Pulmonary artery catheter (PAC)
      for continuous cardiac output and SvO(2) monitoring was inserted before
      anaesthesia. Haemodynamic measurements were recorded after pericardiotomy for
      baseline value. During each coronary artery anastomosis, haemodynamic variables
      were measured at 1,3,5,10, and 15 min after the application of tissue stabilizer
      and after the removal. Vasopressors were used to maintain mean arterial pressure
      (MAP) higher than 60 mmHg. RESULTS: MAP and heart rate (HR) were maintained
      without significant change during the anastomoses of all three arteries. Cardiac
      index (CI), and SvO(2) decreased significantly after stabilizer application in
      all three arteries. CI was below 2.5 l/min/m(2) and SvO(2) was under 70% during
      left circumflex artery (LCX) anastomosis. The decrease in CI and SvO(2) were
      significantly greater during LCX anastomosis. The increase in mean pulmonary
      artery pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) was
      significant only in left anterior descending artery (LAD). Central venous
      pressure (CVP) increased significantly during the anastomosis of all three
      coronary arteries. The differences in MPAP, PCWP and CVP among the three coronary
      arteries were not statistically significant. The highest dose of vasoconstrictor
      was used during LCX anastomosis. CONCLUSIONS: When the coronary anastomoses were
      performed with two deep pericardial stay sutures and octopus tissue stabilizer on
      the beating heart, CI and SvO(2) decreased significantly during all coronary
      artery anastomoses immediately after the stabilizer application and the degree of
      reduction in CI and SvO(2) increased with time, though MAP was maintained
      constantly. CI and SvO(2) during LCX anastomosis were consistently below normal
      values. Therefore close monitoring and proper managements are needed during graft
      anastomoses.

PMID- 15145000
TI  - Automatic connector devices for proximal anastomoses do not decrease embolic
      debris compared with conventional anastomoses in CABG.
AB  - OBJECTIVE: Emboli generated during cardiac surgery have been associated with
      aortic clamping and manipulation. Proximal anastomotic devices are thought to be
      less traumatic by eliminating partial clamping, potentially resulting in fewer
      adverse outcomes. Intra-aortic filtration has been shown to effectively capture
      particulate debris. We compared the amount of debris released using intra-aortic
      filtration and the clinical outcomes between conventionally handsewn and
      automated proximal anastomoses. METHODS: Seventy-seven patients undergoing
      primary coronary artery bypass grafting with cardiopulmonary bypass were enrolled
      in a prospective randomized study. Patients were assigned to the anastomotic
      device Group I (Symmetry Aortic Connector, n = 39) or the conventional handsewn
      anastomosis control Group II (n = 38). Proximal anastomoses were performed before
      cardiopulmonary bypass in both groups. Intra-aortic Filter 1 (EMBOL-X)was
      deployed prior to partial clamping or puncturing the aorta for device application
      and removed after the proximal anastomosis was completed. Prior to cross-clamp
      removal, a second filter was inserted (Filter 2). A core laboratory performed
      quantitative and histologic analyses of the debris captured. Clinical outcomes
      included adverse events, neurocognitive test scores, graft patency, and
      mortality. RESULTS: Preoperative variables and risk factors were not
      significantly different between Groups I and II (EuroSCORE 3.9+/-2.6 vs. 4.2+/
      2.5). Filter analyses showed no significant difference between Groups I and II in
      Filter 1 or 2 for either surface area of particles or total number of particles
      (P> 0.005). There was a significant decrease between Filters 1 and 2 in both
      Groups for surface area of particles (Group I: 18.5+/-23.8 mm2 vs. 10.7+/-16.3
      mm2, P = 0.017; Group II: 15.0+/-15.4 mm2 vs. 6.9+/-.6.5 mm2, P = 0.004), and for
      total number of particles in Group II (8.6+/-3.7 vs. 7.1+/-2.4, P = 0.023). No
      significant differences were observed between Group I (device) and Group II
      (control) outcomes for myocardial infarction, neurocognitive deficit, stroke,
      length of stay, graft occlusion, or mortality. CONCLUSIONS: The application of
      proximal aortic connectors without partial clamping does not reduce particulate
      emboli or affect clinical outcomes compared with conventional anastomoses. Cross
      clamping during cardiopulmonary bypass produces less particulate debris than
      conventional or automated proximal anastomoses performed off-pump, suggesting a
      major source of emboli is the anastomotic process.

PMID- 15144999
TI  - On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein
      70 is released after on-pump surgery.
AB  - OBJECTIVES: The use of cardiopulmonary bypass in coronary artery bypass grafting
      (CABG) may contribute to the postoperative inflammatory response. The molecular
      chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been
      detected both in the myocardium and in the circulation after CABG. In vitro,
      extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing
      that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we
      explored the release of it in 10 patients undergoing CABG with the use of CPB,
      and in 10 patients undergoing off-pump surgery CABG (OPCAB). METHODS: Blood
      samples were taken preoperatively, twice peroperatively, 2 and 6 h
      postoperatively and the next day. Serum analyses were performed by means of
      immunoassays. RESULTS: We detected a significant difference in postoperative
      circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and
      756 pg/ml, respectively, P < 0.01 2 h postoperatively). Interleukin-6 and -8
      increased in all patients, without significant differences between the groups.
      Serum interleukin-10 increased at the end of the operation in 7 of 10 patients
      operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off
      pump patients. Furthermore, in the first group, interleukin-10 correlated with
      the HSP70 concentration at the end of the operation, r = 0.75, P < 0.05. Serum
      markers of myocardial damage were higher in conventional than off-pump patients
      on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 microg/l,
      respectively, P < 0.01. Correspondingly, median creatine kinase-MB was 23.6 and
      7.8 microg/l in on-pump and off-pump patients, respectively, P < 0.001. Peak
      HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1.
      CONCLUSIONS: Significantly more HSP70 was released into the circulation following
      conventional than following off-pump CABG. Circulating HSP70 may indicate
      cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory
      agents, and may be important in the host defence postoperatively.

PMID- 15145001
TI  - Clinical significance of a new Q wave after cardiac surgery.
AB  - OBJECTIVE: The appearance of new Q waves on the electrocardiogram (ECG) after
      cardiac surgery has been traditionally considered a sign of major myocardial
      tissue damage. The aim of this study was to investigate the clinical significance
      of new Q waves appearing following cardiac surgery and to correlate them with the
      release of myocardial cell damage biomarkers. METHODS: 206 consecutive patients
      undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was
      recorded and cardiac troponin I and creatinekinase subfraction MB assayed the day
      before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively
      and every morning until the fifth postoperative day. RESULTS: The incidence of
      new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful
      postoperative course; on the contrary, when ECG changes were coupled with the
      release of myocardial necrosis biomarkers, patients had a complicated
      postoperative course. CONCLUSIONS: The association of a new Q wave and high
      levels of myocardial necrosis biomarkers is strongly associated with
      postoperative cardiac events. On the contrary, the isolated appearance of a new Q
      wave has no impact on the postoperative cardiac outcome.

PMID- 15145002
TI  - Ischemic postconditioning: brief ischemia during reperfusion converts persistent
      ventricular fibrillation into regular rhythm.
AB  - OBJECTIVES: Brief episodes of myocardial ischemia-reperfusion employed during
      reperfusion after a prolonged ischemic insult may attenuate the total ischemia
      reperfusion injury. This phenomenon has been termed ischemic postconditioning. In
      the present study, we studied the possible effect of postconditioning on
      persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat
      heart model. METHODS: Isolated Langendorff-perfused rat hearts (n = 46) were
      subjected to 30 min of regional ischemia and reperfusion. The hearts with
      persistent VF (n = 11) present after 15 min of reperfusion were then randomly
      assigned into one of the two groups: (1) control hearts (n = 6) in which
      perfusion was continued without intervention; (2) postconditioned hearts (n = 5)
      subjected to 2 min of global ischemia followed by reperfusion. Left ventricular
      pressures, heart rate, coronary flow, and electrogram were monitored throughout
      the experiment. RESULTS: Conversion of VF into regular rhythm was observed in all
      hearts subjected to postconditioning. Regular beating was maintained by all
      postconditioned hearts during the subsequent reperfusion. None of the hearts in
      the control group had normal rhythm at the end of the experiment. At the end of
      reperfusion, the left ventricular developed pressure was lower in beating
      postconditioned hearts compared to the hearts that did not develop persistent VF.
      CONCLUSIONS: Ischemic postconditioning possesses strong antiarrhythmic effect
      against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be
      an interesting, novel adjunct strategy to protect the heart.

PMID- 15145003
TI  - Microwave and radiofrequency ablation yield similar success rates for treatment
      of chronic atrial fibrillation.
AB  - OBJECTIVE: To evaluate the influence of two different ablation devices (microwave
      AFx and radiofrequency Medtronic), designed to create linear lesion lines, with
      respect to efficacy and restoration of sinus rhythm (SR). METHODS: Between
      February 2001 and December 2002, 42 patients with chronic, persistent atrial
      fibrillation (AF) >6 months were submitted to different combinations of valve
      surgery (mitral+/-tricuspid, n = 30; mitral and aortic+/-tricuspid
      reconstruction, n = 6 aortic+/-tricuspid, n = 8) and concomitant Maze procedure.
      The biatrial Maze followed the concept of the Cox III procedure, using either
      microwave energy (AFx Lynx) (group I: age 65.8+/-11.9 years, mean duration of AF
      61.9+/-28.9 months, n = 23) or radiofrequency (Medtronic Cardioblate) (group II:
      age 64.1+/-11.1 years, mean duration of AF 53.5+/-49 months, n = 19). RESULTS:
      There was one death with group I (4%), due to liver failure. Both groups were
      comparable with regard to Euro Score, ejection fraction, cross clamp time,
      cardiopulmonary bypass time, ICU (median 1 day in both groups) and hospital stay,
      and type of indication. The preoperative diameter of the left atrium was 69.7+/
      10.8 and 74.0+/-14.3 mm in groups I and II, respectively (P = 0.359). The Maze
      procedure resulted in 23+/-2 and 17+/-1 min additional cross clamp time in groups
      I and II, respectively (P = 0.013). At the 12-month follow up, freedom from AF
      was 81 and 80% in groups I and II, respectively. Twenty percent in group I and
      21% in group II needed a pacemaker (PM), due to sick sinus syndrome (2 versus 2
      cases), AV bloc (2 versus 1 case) and preoperative bradycardia (0 versus 1 case),
      respectively. CONCLUSIONS: The combination of complex valve surgery and Maze
      procedure was safe and reproducible. Following the Cox Maze III line concept,
      microwave and radiofrequency ablation gave similar results even in patients with
      more complex double or triple valve procedures.

PMID- 15145005
TI  - Mid-term results of cardiac autotransplantation as method to treat permanent
      atrial fibrillation and mitral disease.
AB  - OBJECTIVES: The results of current surgical options for the treatment of
      permanent atrial fibrillation (AF) associated with mitral surgery are widely
      different, particularly in very enlarged left atria. The aim of this study was to
      assess the mid-term efficacy of cardiac autotransplantation for this goal,
      through a consistent reduction of left atrium volume and a complete isolation of
      the pulmonary veins. METHODS: From April 2000 to September 2002, 30 patients
      (male/female 5/25) underwent cardiac autotransplantation for the treatment of
      mitral valve disease and concomitant permanent AF (>1 year). Surgical technique
      of bicaval heart transplantation was modified maintaining the connection of
      inferior vena cava in all but three cases. Twenty-eight patients had mitral valve
      replacement and two had mitral valve repair. Associated procedures were: aortic
      valve replacement (6 cases), tricuspid valve repair (2 cases), coronary re
      vascularization (2 cases) and right atrium volume reduction (4 cases). RESULTS:
      No hospital death occurred; 1 patient died 3 months post-operatively for
      pneumonia. At a mean follow-up of 21.1+/-7.7 months (range 6-35), 26 patients
      (89.7%) were in sinus rhythm and 3 (10.3%) in AF. Santa Cruz Score was 0 in 3
      patients, 2 in 2 patients and 4 in the remaining 24 patients (82.7%). Mean left
      atrial diameter and volume decreased from 65.1+/-16.4 mm (range 50-130 mm) to
      49.9+/-8.4 mm (range 37-78) (P < 0.001) and from 118.3+/-68.4 ml (range 60-426)
      to 69.4+/-34.1 ml (range 31-226) (P = 0.001), respectively, after the operation.
      CONCLUSIONS: Cardiac autotransplantation is a safe and effective option for the
      treatment of permanent AF in patients with mitral valve disease and severe
      dilation of left atrium.

PMID- 15145004
TI  - Concomitant anti-arrhythmic surgery, using irrigated cooled-tip radiofrequency
      ablation, to treat permanent atrial fibrillation in CABG patients: expansion of
      the indication?
AB  - OBJECTIVES: The effectiveness of a concomitant anti-arrhythmic surgical procedure
      in coronary artery bypass grafting (CABG) patients with permanent atrial
      fibrillation (AF) was evaluated. METHODS: This prospective study included 36 CABG
      patients, who had a concomitant anti-arrhythmic procedure using irrigated cooled
      tip radiofrequency ablation. Follow-up included a 24 h EKG and ultrasound
      examination at 3, 6, 12 months. RESULTS: Mean (SD) age was 68.7 years (8.0), left
      atrial diameter 44.9 mm (6.7), preoperative duration of AF 67 months (73), left
      ventricular ejection fraction 54% (14), euroscore 5.5 (2.6), number of distal
      anastomoses 3.3 (1.2), aortic cross-clamp time 90 (19)min, extracorporeal bypass
      time 156 (38)min. Thirty-day mortality was 2.8% (1/36). Mean (SD) follow-up was
      25.3 months (17.9). Cumulative survival rates (SE) at 12 and 24 months were 0.94
      (0.04) and 0.90 (0.06). Cumulative postoperative sinus rhythm (SR) rates (SE) at
      6 and 12 months were 0.60 (0.08) and 0.75 (0.08). Restored bi-atrial contraction
      occurred in 73% (19/26) of all SR patients. As a consequence coumadine was
      stopped, after the 6th postoperative month, in 76% (16/21) in this subset of
      patients, corresponding with 44% (16/36) of all study group patients. One patient
      experienced a sick sinus syndrome 12 months postoperatively, for which a DDD
      pacemaker was implanted. Three out of five patients with a preexistent VVI
      pacemaker regained a stable postoperative SR with bi-atrial contraction,
      obviating the need of any pacemaker support.

PMID- 15145006
TI  - Emergency stent-graft placement for hemorrhage control in acute thoracic aortic
      rupture.
AB  - OBJECTIVE: To report mid-term results of stent-graft (SG) implantation in acute
      thoracic aortic rupture as alternative to conventional open surgery with its
      associated high morbidity and mortality rates. METHODS: Out of a series of 69
      patients undergoing thoracic aortic SG implantation since 1998, 24 (mean age 57+/
      19 years, range 20-85-years-old) patients were treated on an emergency basis for
      hemorrhage control. The indication for SG placement was acute traumatic aortic
      rupture in 15 patients, type B dissection with contained rupture in 3 patients,
      penetrating aortic ulcer with periaortic hematoma in 3 patients, and thoracic
      aortic aneurysm rupture in 3 patients. Preoperative assessment was done by
      computed tomography (CT) scanning and echography. Patients were treated in the
      angiography suite by implantation of Excluder (n = 18) Talent (n = 4) Corvita (n
      = 1) and Vanguard (n = 1) self-expanding grafts. Local anesthesia was the most
      frequently used anaesthesiologic technique. RESULTS: Technical success rate of SG
      deployment was 100%. The early postoperative mortality was 12.5% (3 of 24). One
      patient suffered temporary paraplegia (4%). There was no intervention-related
      mortality during the mean follow-up of 34.1 months. Two secondary endoleaks were
      successfully treated with additional SG placement at 2 and 12 months
      postoperative, respectively. CONCLUSIONS: Emergency SG repair to control
      hemorrhage in patients with an acute thoracic aortic rupture is a less-invasive
      attractive and rational treatment option, especially if associated lesions or co
      morbidity may interfere with the surgical outcome. Long-term follow-up results
      will be helpful to clarify procedure durability bounded by material failure and
      postoperative aneurysm or aortic wall remodelling.

PMID- 15145007
TI  - A finite element model of blunt traumatic aortic rupture.
AB  - OBJECTIVE: Blunt traumatic aortic rupture has a scene survival of 2-5% and is
      present in 20% of all automobile fatalities. The manner in which the forces from
      a range of thoracic impacts are transduced through the thoracic cavity to produce
      consistent injury to the aortic isthmus remains uncertain. Our objective was to
      create and evaluate a computer based finite element (FE) model of the aorta and
      observe its behavior during blunt traumatic impacts. METHODS: A finite element
      model of the thorax including details of the heart, aorta and pertinent thoracic
      structures was created and run under the FE code LS-DYNA3D. The motion response
      of the heart following a simulated thoracic impact was extracted from the thorax
      model and applied in a second more detailed model of the heart and aorta in order
      to investigate the stresses acting through the aortic isthmus during simulated
      thoracic impacts. RESULTS: Simulated impact studies show that the predicted peak
      chest compression of the thorax model matched the measured responses from non
      embalmed human cadaver impact studies by Kroell et al., 1974. The more detailed
      heart-aorta model predicted maximum stresses at the isthmus and pulmonary artery
      bifurcation the sites of most common trauma injury. CONCLUSIONS: Analysis of the
      response of the finite element heart-aorta model during blunt thoracic trauma
      demonstrates its potential for predicting major vessel injury. The model will be
      helpful in the design of impact protection systems.

PMID- 15145008
TI  - Current indications and results of VATS in the evaluation and management of
      hemodynamically stable thoracic injuries.
AB  - OBJECTIVE: Thoracic injuries are among the most severe forms of trauma and also a
      leading cause of morbidity and mortality. Video Assisted Thoracic Surgery (VATS)
      has recently provided an alternative method to simultaneously diagnose and manage
      patients sustaining chest injuries. We analyze our experience with VATS in the
      setting of thoracic trauma detailing indications for exploration, procedures
      performed and results of surgery. METHODS: A 6-year single institution review of
      patients undergoing VATS due to injuries sustained from both blunt and
      penetrating chest trauma at a Level I trauma center and university teaching
      hospital. Comparisons were made between groups of blunt and penetrating trauma as
      to Injury Severity Score (ISS), presence of extra-thoracic injuries, initial
      thoracostomy drainage and length of postoperative stay. RESULTS: VATS was
      successfully performed in 19 consecutive patients without conversion to
      thoracotomy. Indications for exploration included acute hemorrhage, retained
      hemothorax, suspected diaphragmatic injuries (DI), suspected cardiac injury,
      intra-thoracic foreign body, persistent airleak and chronic empyema. Procedures
      performed consisted of evacuation of retained hemothorax, hemostasis of intra
      thoracic bleeders, repair of DI, wedge lung resections and decortication. Mean
      postoperative length of stay was 5.86 days. There were no morbidities. One
      patient with severe intra-abdominal injuries expired on the first postoperative
      day. CONCLUSION: In hemodynamically stable patients with thoracic injuries, VATS
      provides an accurate assessment of intra-thoracic organ injury and can be
      utilized to definitively and effectively manage injuries sustained as a result of
      blunt or penetrating thoracic trauma. VATS should be used with caution in
      patients sustaining severe and life threatening intra-abdominal injuries.

PMID- 15145009
TI  - Incidence of chest wall paresthesia after video-assisted thoracic surgery for
      primary spontaneous pneumothorax.
AB  - OBJECTIVE: Video-assisted thoracic surgery (VATS) is an established treatment for
      recurrent or complicated primary spontaneous pneumothorax (PSP). However, a
      proportion of patients still complains of chronic pain or discomfort after VATS
      pleurodesis. We aimed to investigate if paresthesia is a distinct component of
      the post-operative discomfort in patients receiving VATS for PSP. METHODS:
      Telephone interviews were conducted with 52 patients who had received VATS
      pleurodesis for PSP in our institute during a defined 24 month period. A
      standardized questionnaire was used to identify paresthetic discomforts which the
      patients themselves could distinguish from their wound pain. Responses were
      obtained from 51 patients (42 male, 9 female) with a mean age of 24.1 years
      (range 14-63 years), giving a response rate of 98.0%. RESULTS: With a median
      observation time of 19 months (range 2-24 months), 27 patients (52.9%) reported
      experiencing paresthesia as a post-operative complication distinct from their
      wound pain. The most commonly described characteristics of the paresthesia were
      'pins and needles' (37.0%), 'numbness' (25.9%) or a sensation of abnormal
      'swelling' in the chest wall (11.1%). Although only two of the affected patients
      (7.4%) described the paresthesia as 'severe', consequent functional disturbances
      in daily life were noted by seven patients (25.9%), and 11 patients (40.7%)
      actively sought medical or alternative, holistic therapies to relieve the
      paresthesia. Eight (21.0%) of the 38 patients followed-up for over 12 months
      after surgery still experienced the paresthesia. CONCLUSIONS: Although it should
      not detract from the proven advantages of VATS, paresthesia in the chest wall
      represents a distinct but previously overlooked post-VATS complication. It is a
      potential source of significant post-operative morbidity, and may run a chronic
      course in some patients. Further study is warranted to elucidate its mechanisms
      and optimum management.

PMID- 15145011
TI  - Management of congenital tracheal stenosis.
AB  - OBJECTIVES: Congenital tracheal stenosis is a rare disease. Various methods for
      treatment exist but there is still much debate as to the appropriate surgical
      procedure. We present our surgical experiences of patch tracheoplasty and slide
      tracheoplasty as viable methods for the treatment of congenital tracheal
      stenosis. METHODS: From 1994 to 2002, 13 patients were diagnosed with congenital
      tracheal stenosis. Eight patients (7 symptomatic and 1 asymptomatic) had their
      stenosis corrected, three by means of pericardial patch tracheoplasty, four by
      slide tracheoplasty, and one by resection and anastomosis. Concomitant operations
      were performed on six patients to treat congenital cardiovascular disease. Five
      patients showing no significant symptoms did not undergo tracheal surgery and
      received only cardiac procedures. A retrospective review of the hospital course,
      complications, and long-term results was conducted. RESULTS: Among the patch
      tracheoplasty group, every patient suffered from granulation tissue formation.
      One patient died of respiratory acidosis and one was hospitalized due to
      recurrent granulation tissue, which required frequent bronchoscopy. The third
      patient from this group is free of all symptoms. Among the slide tracheoplasty
      group, one patient died of anastomosis disruption. The three remaining patients
      are alive and well. The one patient who received resection and anastomosis is
      alive without symptoms. CONCLUSIONS: Surgical repair of long-segment congenital
      tracheal stenosis exhibited high mortality and morbidity rates. Every patient
      that underwent pericardial patch tracheoplasty suffered from troublesome
      granulation tissue. As slide tracheoplasty provided relatively good results in
      the short and mid-term follow-up periods, it seems to be a preferred method for
      the treatment of long-segment congenital tracheal stenosis.

PMID- 15145010
TI  - Role of endotracheal stenting in tracheal reconstruction surgery-retrospective
      analysis.
AB  - OBJECTIVE: To review a single institution experience with tracheal stenosis
      treatment and to define a role of endotracheal stenting in tracheal
      reconstruction surgery. PATIENTS AND METHODS: In the period between January 1991
      and January 2003, 163 patients underwent tracheal reconstruction. There were 114
      males and 49 females in age range from 0.5 to 79 years (mean 43.2 years).
      Indications for reconstruction were: posttracheostomic (PostTS) and
      postintubation (PostINT) stenoses in 111 cases, tumor-stenosis in 24 cases,
      tracheo-esophageal fistulas (T-Efist) in 17 cases, traumatic laesions in six and
      functional stenosis in five cases. For these indications, the following
      procedures were performed: segmental tracheal resection in 87 cases, stenting in
      68 cases (by our own modification of Montgomery T-tube in 65 cases and by other
      traditional endo-stents in three cases). Primary suture of traumatic tracheal
      wall was performed in five cases. Three cases involved laser intervention and
      tumor resections, respectively. RESULTS: Segmental tracheal resection (n = 87)
      was successful in almost all the cases (96%). T-tube was applied in 65 cases; the
      indications included: PostTS and PostINT stenoses in 38 cases, tumors in 17
      cases, T-E fistulas in seven cases and functional stenosis in three cases. Twenty
      seven patients (41.6%) were successfully treated by this modality. In 19 patients
      (29.2%), the stenting is still continuing, but they are candidates for extraction
      of the T-tube in near future. In 19 patients (29.2%) with malignant stenoses, the
      T-tube was applied only as a palliation. All these patients died due to their
      underlying malignant disease; the follow-up ranged from 2 to 18 months.
      CONCLUSION: Tracheal stenosis is a serious, life-threatening disease with
      increasing incidence. In our study, the best results were achieved by segmental
      tracheal resection. However, the endotracheal stenting is the method of choice,
      when the segmental resection cannot be performed. The management of tracheal
      stenosis reconstruction by our own modification of Montgomery T-tube is being
      presented.

PMID- 15145012
TI  - Management of postpneumonic empyemas in children.
AB  - OBJECTIVES: Despite continued improvement in medical therapy, pediatric empyema
      remains a challenging problem for the surgeon. Multiple treatment options are
      available; however, the optimal therapeutic management has not been elucidated.
      The aim of this study is to assess different treatment options in the management
      of postpneumonic pediatric empyemas. METHODS: A retrospective review was
      performed of pediatric patients admitted to Dicle University School of Medicine
      Thoracic and Cardiovascular Surgery Department between 1990 and 2002, with the
      diagnosis of empyema. Data tabulated included patient demographics, presentation,
      treatment and outcome. RESULTS: There were 515 children (289 boys and 226 girls)
      with a mean age of 4.7 ranging from 18 days to 15 years. Empyema was secondary to
      pneumonia in all children. The most common radiologic finding was pleural
      effusion in 285 patients (55.32%). Staphylococcus aureus was the most frequently
      encountered organism and found in 105 patients (20.38%). Pleural fluid cultures
      were negative in 195 patients (37.86%). In addition to antibiotic therapy,
      initial treatment included serial thoracenthesis (n = 29), chest tube drainage
      alone (n = 214), chest tube drainage with intrapleural fibrinolytic therapy (n =
      72), chest tube drainage with primary operation (n = 191), and primary operation
      without chest tube drainage (n = 9). Overall response rate with fibrinolytic
      treatment (complete and partial response) was obtained in 58 patients. In
      addition to decortication pulmonary resections were performed in 12 patients.
      Overall mortality rate was 1.55%. There was no operative mortality. Postoperative
      morbidity included wound infection in 21, delayed expansion in 8, and atelectasis
      in 35 patients. CONCLUSIONS: Multiple therapeutic options are available for the
      management of pediatric empyema. Depending on stages, every option has a role in
      the treatment of postpneumonic pediatric empyema. In the absence of
      bronchopleural fistula, intrapleural fibrinolytic treatment should be tried in
      all patients with multiloculations in stage II empyema. In the absence of
      pneumonia, decortication for empyema is a safe approach with low mortality and
      morbidity rates.

PMID- 15145013
TI  - The surgical treatment of the intrathoracic migration of the gastro-oesophageal
      junction and of short oesophagus in gastro-oesophageal reflux disease.
AB  - OBJECTIVES: In the rush to implement laparoscopic surgery for gastro-oesophageal
      reflux disease (GORD), the necessity to treat a short oesophagus with dedicated
      techniques was not always adequately considered. The aim of this study was to
      define the frequency, patterns and surgical treatment of the intrathoracic
      migration of the g-o junction and short oesophagus in GORD. METHODS: Between 1980
      and 2003 our group indicated surgery only for severe and complicated GORD and for
      drawbacks of medical therapy. Preoperatively patients underwent clinical
      instrumental work up. The various degrees of the intrathoracic migration of the g
      o junction were classified according to the barium swallow. A total of 319
      patients operated upon were grouped according to the periods 1980-1991 and 1992
      2003 with 149 and 170 patients, respectively. In the first period only 'open'
      procedures were performed; the Collis gastroplasty in addition to the antireflux
      procedure was performed when reduction of the g-o junction in the abdomen
      required excessive tension. In the second period mini-invasive techniques were
      progressively introduced. During laparoscopy, the relationship between the g-o
      junction and the hiatus, and the need to elongate the oesophagus, was assessed by
      intraoperative oesophagoscopy. RESULTS: The Collis gastroplasty was performed in
      29% in the first period and in 23% in the second period. Radiology was a strong
      predictor of the necessity to elongate the oesophagus. In the second period,
      global long-term results improved with respect to the first period; P = 0.047
      (first period satisfactory 82%, poor 18%, median FU 84, 12-252 months; second
      period satisfactory 93%, poor 7%, median FU 34, 6-126 months). In the second
      period, Collis-Nissen and Collis-Belsey procedures had satisfactory results in
      80% and poor in 20%. CONCLUSIONS: In surgery for severe GORD, the Collis
      procedure is required in 23% of operations; radiology helps to plan surgery;
      intraoperative endoscopy avoids unnecessary oesophageal lengthening.

PMID- 15145014
TI  - Long-term results and quality of life after surgery for oesophageal achalasia:
      one surgeon's experience.
AB  - OBJECTIVE: To assess the long-term results and health-related quality of life in
      patients undergoing surgery for oesophageal achalasia. METHODS: Thirty-nine
      patients with achalasia (25 males, mean age 42+/-13 years) underwent open-Heller
      myotomy and Dor fundoplication by the same surgeon. Long-term results were
      assessed by imaging, endoscopy, manometry, pH-metry, and Short Form 36 and
      Nottingham Health Profile questionnaires whenever applicable. Six patients were
      at radiological stage I, 20 were at stage II, 2 at stage III and 11 at stage IV.
      Dysphagia and regurgitation were scored according to the four-grade
      classification (1=no symptoms; 4=persistent symptoms). Pulmonary symptoms were
      present in six patients. Lower oesophageal pressure was 30+/-34 mmHg. Six
      patients had undergone previous pneumatodilation. RESULTS: No procedure related
      mortality was recorded. Mean follow-up was 107+/-30 months (54-177). Preoperative
      to 5-year postoperative mean decrement in lower oesophageal sphincter pressure
      was 12.3+/-8.3 mmHg (P < 0.001) in oesophageal width was 11.5+/-7.1 mm (P <
      0.001) in dysphagia 1.8+/-0.8 (P < 0.001) and regurgitation 1.4+/-0.7 (P < 0.001)
      Four patients presented relapse dysphagia and two of those were re-operated upon.
      Three patients developed acid reflux, which was satisfactorily treated with
      proton-pump inhibitors. Preoperative to 4-year postoperative quality of life
      scores were available for 20 patients. Questionnaires showed a significant
      improvement (P < 0.001) especially in all psychosocial domains, which were
      correlated with postoperative dysphagia score and lower oesophageal sphincter
      pressure. CONCLUSION: Heller myotomy and Dor fundoplication is a safe and
      effective procedure that improves symptoms, functional status and especially
      psychosocial aspect of quality of life in the long term in oesophageal achalasia.

PMID- 15145015
TI  - Comparison of manual and mechanical cervical esophagogastric anastomosis after
      esophageal resection for squamous cell carcinoma: a prospective randomized
      controlled trial.
AB  - OBJECTIVE: The use of a circular stapler in cervical esophagogastric anastomosis
      remains controversial. This study was to compare the postoperative and long-term
      results of manual and mechanical techniques for cervical esophagogastric
      anastomosis after resection for squamous cell carcinoma. METHODS: A prospective
      randomized controlled trial was undertaken in 63 patients with curatively
      resectable squamous cell cancer of the thoracic esophagus between 1996 and 1999.
      Patients were randomized to receive either a hand-sewn (32 patients) or circular
      stapled (31 patients) cervical esophagogastric anastomosis. RESULTS: The mean
      operating time was longer when the hand-sewn method was used (524 vs. 447 min, P
      < 0.001). Anastomotic leakage was noted in seven patients (22%) in the hand-sewn
      group and eight patients (26%) in the stapler group (P = NS). Hospital mortality
      occurred in four patients (13%) of the hand-sewn group and in three patients
      (10%) of the stapler group (P = NS). After the operation, four patients (14%) in
      the hand-sewn group and five patients (18%) in the stapler group developed a
      benign esophageal stricture (P = NS). The mean follow-up time was 24 months, and
      the rates of freedom from benign stricture and survival were comparable in each
      group. CONCLUSIONS: Performing cervical esophagogastric anastomoses using a
      circular mechanical stapler had a shorter operating time and a comparable outcome
      to the hand-sewn method. The circular mechanical stapler could be used as an
      alternative for cervical esophagogastric anastomosis after resection for
      esophageal squamous cell cancer.

PMID- 15145016
TI  - Objective definition and measurement method of ground-glass opacity for planning
      limited resection in patients with clinical stage IA adenocarcinoma of the lung.
AB  - OBJECTIVE: The standard operation for patients with stage IA lung adenocarcinoma
      is considered to be a lobectomy. Recently, some researchers have reported that
      patients with tumors showing greater proportions of ground-glass opacity (GGO) at
      computed tomography (CT) could be candidates for limited resection, because of
      its less aggressive nature. However, the lack of a precise definition or standard
      measuring method of GGO prevents its general use as an index for planning limited
      resection. Therefore, we attempted to define GGO based on CT number and measured
      it more objectively. METHODS: Between 1998 and 2001, 90 patients with clinical
      stage IA adenocarcinoma, who underwent standard or intentional limited resection
      and whose images of chest high-resolution CT were preserved in Digital Imaging
      and Communications in Medicine (DICOM) format, constituted the study population.
      The tumor shadow seen on the solid window (WL, -160HU; WW, 2HU) was regarded as
      the central solid area of the tumor seen on the lung window, and GGO was defined
      as the whole tumor area with the exception of the central solid area. Each area
      was measured using Scion Image (Scion Corp., Frederick, MD). We analyzed the
      relationship between the proportion of GGO and both of pathologic findings and
      recurrence. RESULTS: Among the 90 tumors, 31 (34.4%) were calculated to have a
      GGO area greater than or equal to 50%. Of these, 27 (87%) tumors were
      bronchioloalveolar carcinoma. Lymphatic and vascular invasions, or nodal
      involvement were found only in patients with a smaller proportion of GGO (<50%)
      (P < 0.05). During the follow-up period (median 36 months), recurrences occurred
      in eight patients who were diagnosed as having tumors showing smaller proportion
      of GGO (<50%). CONCLUSIONS: Tumors with a greater proportion of GGO measured by
      our method are thought to have a less invasive nature. Our objective measuring
      method of GGO could be useful for future multicenter trials to elucidate the
      value of limited resection for clinical stage IA adenocarcinoma based on the
      proportion of GGO.

PMID- 15145017
TI  - Prognosis of patients with non-small cell lung cancer with isolated brain
      metastases undergoing combined surgical treatment.
AB  - OBJECTIVE: To compare survival of patients with isolated synchronous and
      metachronous brain metastases from non-small cell lung cancer (NSCLC) after
      combined surgical treatment. METHODS: A total of 991 patients underwent surgical
      resection of primary NSCLC between January 1994 and November 1999. Out of these,
      32 patients (21 males and 11 females) were further treated for isolated brain
      metastases. In a retrospective survey, the outcome of patients with either
      synchronous (group 1, n = 16) or metachronous (group 2, n = 16) brain metastases
      was evaluated. Five patients out of each group received either adjuvant or neo
      adjuvant chemotherapy. Data analysis includes descriptive statistics, Wilcoxon
      test, Kaplan-Meier method and Cox's proportional hazards model. RESULTS: There
      was no significant difference in local tumour stage and histology of the primary
      tumour between both groups. Median of the disease free interval (DFI) after
      primary lung surgery (group 2) was 10 months, range 3-60 months. Median survival
      after lung surgery was 8.5 months in group 1 and 16.4 months in group 2 (P =
      0.094). Median survival after cerebral procedures was 9.3 and 6.2 months,
      respectively (P = 0.127). Estimated survival rates by Kaplan-Meier method after
      cerebral procedures operation in group 1 were 37.5% at 1 year, 25.0% at 2 years
      and 18.8% at 5 years; in group 2 estimated survival rates were 31.3% at 1 year,
      15.6% at 2 years and 0% at 5 years (P = 0.148). Calculated survival rates after
      lung surgery were identical in group 1; in group 2 survival rates were 62.5, 43.8
      and 18.8% at 1, 2 and 5 years, respectively (P = 0.101). In the univariate model,
      none of the following variables had effect on survival: sex, age, T stage of the
      tumour, nodal status, timing of metastatic lesions, number of cerebral
      metastases, complete resection of primary tumour and histological type.
      Multivariate analysis did not reveal any risk factor, which significantly
      predicted survival. DFI did not correlate with survival of patients in group 2.
      CONCLUSIONS: Once isolated synchronous or metachronous brain metastases from
      NSCLC have developed, there is no difference in prognosis after combined surgery
      between analysed groups. This questions the value of lung resection in patients
      with isolated synchronous brain metastases.

PMID- 15145018
TI  - Skip mediastinal nodal metastases in non-small cell lung cancer.
AB  - OBJECTIVE: To reveal the incidence and clinical significance of mediastinal nodal
      metastases without N1-station nodal metastases ('skip-N2 metastases') in non
      small cell lung cancer (NSCLC). METHODS: A total of 450 NSCLC patients who
      underwent tumor resection with a systemic mediastinal nodal dissection were
      retrospectively reviewed. p53 status and proliferative activity represented as
      proliferative index (PI) were also examined immunohistochemically. RESULTS: Skip
      N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334
      patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The
      postoperative survival of skip-N2 patients was almost same as that for patients
      with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly
      more frequent in male patients and squamous cell carcinoma patients. In addition,
      the mean PI for tumor with skip-N2 metastases was significantly higher than that
      for any other pathologic nodal (pN)-status diseases. Combined with histologic
      type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing
      lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without
      N1-nodal involvement. CONCLUSIONS: N1 nodal status is not a useful predictor of
      N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18%
      patients showing no N1-nodal involvement. However, N1 node-guided dissection
      might be performed in patients with adenocarcinoma showing lower PI, because the
      incidence of skip-N2 metastases was extremely low.

PMID- 15145019
TI  - Right diaphragmatic rupture and hepatic hernia: a rare late sequela of thoracic
      trauma.

PMID- 15145020
TI  - Lung cancer presenting as a giant tumor of the thoracic wall.

PMID- 15145021
TI  - Massive primary chest wall chondrosarcoma.

PMID- 15145022
TI  - Periaortic lymphoma mimicking aortic aneurysm.

PMID- 15145023
TI  - Successful treatment of methicillin-resistant Staphylococcus aureus (MRSA)
      mediastinitis in a heart transplant recipient.
AB  - We report on the first case of successfully treated severe methicillin-resistant
      Staphylococcus aureus (MRSA) mediastinitis after heart transplantation. The
      therapy consisted of wrapping of the heart with the transposed greater omentum, 4
      week local irrigation and prolonged aggressive antibiotic therapy with vancomycin
      and linezolid.

PMID- 15145024
TI  - About the neuroprotective effects of FK-506, l-carnitine and azathioprine on
      spinal cord ischemia-reperfusion injury.

PMID- 15145026
TI  - Surgical assistants and working time directives.

PMID- 15145028
TI  - Therapeutic strategy of papillary cystic and solid neoplasm (PCSN): a rare non
      endocrine tumor of the pancreas in children.
AB  - Papillary-cystic and solid neoplasm (PCSN) are rare tumors. Two personal
      observations and a review of the literature are presented with a total of 44
      pediatric patients in addition to a total of 67 published cases in the review of
      Cohen (Pediatr. Surg. Int. 6 (1991) 128) and Snadjauf (Eur. J. Pediatr. Surg. 9
      (1999) 416). Overall, PCSN shows a clear predominance in females and only
      occasionally occurs in males. Typically they grow to a large tumor mass with
      minimal symptoms. Their histologic and immunocytologic characteristics cause
      diagnostic difficulties, especially on frozen sections of small biopsies. The
      tumors are assumed to origin from pluripotent stem cells and present as tumors of
      low malignancy with a favorable prognosis. Nevertheless 10 children have been
      reported to develop metastases, 5 have demonstrated an invasive growth pattern
      and 4 local recurrence. But only two of the 111 pediatric cases have died from
      their tumor burden. Treatment of choice is a complete surgical resection, which
      is true for the primary tumor and for metastases as well as local recurrences. In
      our 2 patients one had spleen-conserving left pancreatic resection and one
      mesopancreatectomy with roux-en-y-reconstruction leading to long-term cure.
      Adjuvant therapy in curative resected patients is unnecessary and does not appear
      to improve prognosis.

PMID- 15145029
TI  - Management of primary malignant epithelial parotid tumors.
AB  - Parotid cancers are infrequently encountered. These tumors carry a prolonged risk
      of recurrence and metastasis. Controversies surrounding pre-treatment evaluation
      by imaging and fine needle aspiration, utility of operative frozen section are
      partly resolved. Though surgery remains the mainstay of treatment, radiation is
      being recognized as a useful adjuvant. Facial nerve preservation is one of the
      important goals at surgery. The role of chemotherapy is still investigational.
      The prognosis and necessity of elective neck treatment are mainly guided by the
      tumor grade and stage.

PMID- 15145031
TI  - Diagnostic imaging of cystic pancreatic neoplasms.
AB  - Cystic pancreatic neoplasms are being diagnosed with growing frequency due to
      improving imaging technologies and increasing clinician awareness. Distinguishing
      cystic neoplasms from pseudocysts and discriminating among the various cystic
      neoplasms is essential to appropriate management. The backbone of diagnosis of
      these tumors continues to be cross-sectional imaging by CT and MRI. Despite
      refinements in technology and significant progress in characterizing these
      lesions, the overall accuracy of CT and MR is limited. EUS, especially as means
      of FNA, will have an increasing role in the evaluation of selected cases as
      experience grows. No radiologic investigation can reliably distinguish cystic
      neoplasms from pseudocysts nor differentiate among cystic neoplasms in all cases.
      For uncertain lesions, surgeons should favor either careful observation with
      serial imaging or surgical resection.

PMID- 15145030
TI  - Airway stenting for unresectable esophageal cancer.
AB  - Because of the close anatomical relationship between the upper esophagus and the
      tracheobronchial tree, many patients with advanced esophageal cancer will suffer
      from airway complications. These include airway stenosis or esophago-respiratory
      fistulation. Airway stenting is proven to offer effective palliation for patients
      with both these complications. When managing such patients, the thoracic surgeon
      faces different options in terms of pre-stenting investigation, choice of stents
      and stenting strategy. Although airway stenting is a safe and effective procedure
      in experienced hands, there are nonetheless complications which await the unwary.
      This review discusses the currently available options for airway stenting in
      these patients, and offers practical advice on avoiding the pitfalls.

PMID- 15145032
TI  - Biological and biophysical principles in extracorporal bone tissue engineering.
      Part I.
AB  - Advances in the field of bone tissue engineering have encouraged physicians to
      introduce these techniques into clinical practice. Bone tissue engineering is the
      construction, repair or replacement of damaged or missing bone in humans or
      animals. Engineering of bone can take place within the animal body or
      extracorporal in a bioreactor for later grafting into the body. Appropriate cell
      types and non-living substrata are minimal requirements for an extracorporal
      tissue engineering approach. This review discusses the biological and biophysical
      background of in vitro bone tissue engineering. Biochemical and biophysical
      stimuli of cell growth and differentiation are regarded as potent tools to
      improve bone formation in vitro. The paper focuses on basic principles in
      extracorporal engineering of bone-like tissues, intended to be implanted in
      animal experiments and clinical studies. Particular attention is given in this
      part to the contributions of cell and material science to the development of bone
      like tissues. Several approaches are at the level of clinical applicability and
      it can be expected that widespread use of engineered bone constructs will change
      the surgeon's work in the near future.

PMID- 15145034
TI  - Facial scoliosis due to sternocleidomastoid torticollis: a cephalometric
      analysis.
AB  - Facial scoliosis can be caused by either the plagiocephaly which arises from
      unilateral coronal suture synostosis, or by the effects of sternocleidomastoid
      torticollis. Despite publications which have presented the key clinical and
      radiographic craniofacial differentiating features, confusion between the two
      still persists. This report presents the essential cephalometric features found
      in sternocleidomastoid torticollis, which may be applied to confirm the diagnosis
      in those cases which present late, and which do not exhibit the characteristic
      features of synostosis.

PMID- 15145033
TI  - Odontogenic myxoma: a clinicopathological study of 33 cases.
AB  - Odontogenic myxoma, a rare tumour that occurs in the jaws, has been reported to
      be the second commonest odontogenic tumour in many countries. Few studies,
      however, provide detailed clinicopathological findings of a large series of cases
      and no study so far has attempted to calculate the incidence of this condition.
      Retrospective and prospective studies were carried out in Tanzania from 1982 to
      1998 (16 years) and 1999 to 2002 (4 years), respectively. A total of 33 cases of
      myxomas were found with a male:female ratio of 1:1.83. Most of the tumours were
      located in the mandible compared to the maxilla and were predominantly
      multilocular. Pain, diasthesia, ulceration, invasion of the soft tissues and
      tooth mobility were among the symptoms that patients presented with although the
      majority had no clinical signs or symptoms. Based on the prospective study only,
      an annual incidence of 0.07 per million can be ascertained. Late reporting was a
      common feature in this group of patients. Radical surgery with resection of the
      tumour with a safe margin is advocated.

PMID- 15145035
TI  - Closed lock (MRI fixed disc): a comparison of arthrocentesis and arthroscopy.
AB  - Twenty-six patients with a sudden-onset of persistent limited mouth opening and
      with MRI signs of articular discs fixed to the glenoid fossa were studied. After
      unsuccessful non-surgical treatment, arthroscopy with sodium hyaluronate infusion
      was performed in 16 joints. Follow-up ranged from 24 to 60 months (mean: 30.3
      months). All patients were clinically assessed preoperatively, and at 1, 3, 6, 9,
      12, 18 and 24 months postoperatively. The clinical variables analysed were: joint
      pain using a visual analogue scale (VAS) (1-15), joint noises (clicking, crepitus
      or none), history of locking, duration of the symptoms, maximal interincisal
      opening (MIO), maximal protrusive movement (MP) and maximal contra-lateral
      movement (ML). MRI images were obtained preoperatively to analyse the
      morphological and dynamic characteristics of the temporomandibular joint. Eight
      of the patients who refused to undergo arthroscopy were treated with
      arthrocentesis. These patients were studied following the same criteria as stated
      above. Mean age of the group was 24.3 years (16-35 years). 20 patients were
      female and 6 male. The preop-MRI examination revealed a normal disc position in
      16 joints and an anteriorly displaced disc in 10 cases. All of the discs were
      fixed to the glenoid fossa preventing an anterior translation of the condylar
      head. After non-surgical treatment only two patients improved while all the other
      patients showed a severe decrease in the MIO (mean 23.3 +/- 2.2 mm), LM (3.8 +/-
      1.4) and a high pain level (9.7 scale). Sixteen patients underwent arthroscopy. A
      significant reduction in pain was noted after arthroscopy. Furthermore, a
      significant increase in MMO and LM was demonstrated postoperatively. Arthroscopic
      findings included the presence of adherences and synovitis. Eight patients who
      refused arthroscopy were treated with TMJ arthrocentesis. All such patients
      improved their symptoms postoperatively. In conclusion both TMJ arthroscopy and
      arthrocentesis give good results upon treating patients with anchored disc
      phenomenon (ADP).

PMID- 15145037
TI  - Further malignancy in field change adjacent to osseointegrated implants.
AB  - The role of endosseous implants in oral rehabilitation following ablation of oral
      tumours is established, however the oncological review of these patients has
      rarely been discussed in the literature. We describe two cases where second
      primary malignancy in the peri-implant tissues necessitated further major
      resections. In both cases, the initial clinical appearance and histology
      suggested peri-implantitis. These cases demonstrate that second primary
      malignancy can masquerade as benign peri-implant complications and that a high
      degree of vigilance is required. Fixed prostheses should be regularly removed,
      especially in patients who have field change.

PMID- 15145036
TI  - New proposal for T classification of gingival carcinomas arising in the maxilla.
AB  - When the current T classification of the UICC (1987 and 1997) is used to stage
      carcinomas arising the upper alveolus and gingival and hard palate, most cases
      are classified as T4 because of their anatomic characteristics, similar to
      carcinomas arising in the lower alveolus and gingiva. This study compared the
      following two methods for classifying the T stage of maxillary carcinomas: (1)
      the original T classification criteria proposed by the UICC (1987 and 1997), and
      (2) a new T classification criteria, called the sinus and nasal floor (SNF)
      criteria. We found that the SNF criteria were more closely related to tumor
      control and survival than were the UICC criteria in patients with carcinomas
      arising in the upper alveolus and gingival and hard palate. Increased use of the
      SNF criteria is expected to improve staging of gingival tumors arising in the
      maxilla and increase the accuracy of diagnosis, especially of T4 tumors.

PMID- 15145038
TI  - Bacteremia after plate removal and tooth extraction.
AB  - Our aim was to investigate the occurrence of bacteremia associated with removal
      of a semirigid osteosynthesis plate and an adjacent third molar. Ten patients
      with fixed mandibular angle fracture were bacteriologically sampled from the
      second molar's distal gingival pocket, from the third molar's extraction socket
      and from the osteosynthesis plate. Blood samples from the ante-cubital vein were
      taken 10 times until 30 min postoperatively. Established culture, isolation and
      identification methods for the bacterial species were used. Bacteremia was
      detected in 60% of the subjects, most frequently 1.5 min after removal of the
      plate (20%) and 1.5 and 5 min after extraction of the tooth (20%), but also 10
      min (10%) and 30 min (10%) postoperatively. 13 different bacterial species or
      groups were isolated, mean 2.5 +/- 1.9 per bacteremia-positive subject. The
      majority (85%) were anaerobes with Actinomyces, Campylobacter and Lactobacillus
      species predominating. In all the blood culture-positive cases the corresponding
      species was also recovered from one or more of the oral samples. These results
      show that oral surgical procedures are associated with a high frequency of
      longstanding anaerobic bacteremia, which could be harmful in patients at risk.

PMID- 15145040
TI  - Quantitative assessment of early healing of intramembranous and endochondral
      autogenous bone grafts using micro-computed tomography and Q-win image analyzer.
AB  - Micro-computed tomography (microCT) is a new tool to image and quantify
      trabecular bone. The aim of this study is to compare the two measurement methods
      when evaluating the early healing of intramembranous (IM) and endochondral (EC)
      autogenous bone grafts using micro-computed tomography and Q-win computer image
      analyzer. Twelve critical size (15 mm x 10 mm) defects were created in rabbit
      mandibles bilaterally. Six defects were grafted with autogenous EC bone; six
      defects were grafted with autogenous IM bone. Three weeks post-surgery, the
      defects were retrieved for microCT imaging analysis and histological evaluation.
      Results showed a significant correlation (r = 0.96, P < 0.0001) between microCT
      and Q-win in measuring the volume of new bone and graft bone in the mandibular
      defects after 3 weeks of early healing. There were distinct differences between
      IM bone and EC bone grafts in 2D and 3D features of graft bone maintenance as
      well as new bone formation. MicroCT imaging is a non-destructive, fast and
      precise procedure that allows for quantitative evaluation of the early healing of
      IM and EC autogenous bone grafts in membranous bone defects.

PMID- 15145039
TI  - Orbital floor reconstruction with poly-L/D-lactide implants: clinical,
      radiological and immunohistochemical study in sheep.
AB  - In this study the reconstruction capacity of orbital wall in sheep was evaluated
      when poly-L/D-lactide (PLDLA96) implants were used for large blow-out defects in
      18 sheep. The contralateral side, where the defects healed spontaneously, served
      as controls. The follow-up was 12, 16, 22 and 36 weeks. Healing was evaluated
      clinically, radiologically, histologically and immunohistochemically.
      Physiochemical properties of the implants were also studied. At first, the
      implants were surrounded by elastic capsules, which gradually ossified. At 36
      weeks, 60% were still visible and deformed but surrounded by bone. Light
      microscopy revealed a low grade inflammatory reaction. Expression of Tn-c and cFn
      was intense throughout the study. Shear strength decreased gradually and was not
      measurable after 16 weeks. Crystallinity increased steadily from 1.5 to 29.30%
      and molecular weight decreased from 49,000 to 4186. In CT, the final bony defect
      was smaller in the reconstructed sides than in the controls. Based on this study
      it can be concluded that PLDLA96 implant provokes a local inflammation, which
      does not prevent bone healing. The deformation of the implant, however, indicates
      that this PLDLA96 plate is not suitable for orbital floor reconstruction.

PMID- 15145042
TI  - Topographic anatomy of the inferior wall of the maxillary sinus in Koreans.
AB  - Knowledge of the relationship between the root apex and the inferior wall of the
      maxillary sinus are crucial for diagnosing and treating a sinus pathosis as well
      as in assisting in dental implantation. Therefore, identifying the proximity
      between the root apex and the inferior wall of the sinus and clarifying the
      cortical thickness of the inferior wall of the sinus is essential for determining
      the topography of a spreading dental infection into the maxillary sinus.
      Accordingly, knowledge of the topography between the root apex and the inferior
      wall of maxillary sinus is important for diagnosing and planning dental
      implantation, endodontic procedures, and orthodontic treatment. This study was
      undertaken to clarify the morphological and clinical characteristics of the
      maxillary sinus, particularly the inferior wall of the sinus in Koreans, and to
      identify the relationship between the inferior wall of the maxillary sinus and
      the roots of the maxillary teeth. Twenty-four sides of the maxillae of hemi
      sectioned Korean heads were used in this study. All specimens were decalcificated
      and sectioned coronally. On the sectioned specimens, 21 items were measured using
      an image analyzing system. The distances between the each root apex and the
      inferior wall of the maxillary sinus were measured. The distance from the root
      apex to the inferior wall of the sinus was the shortest in the second molar area
      and the longest in the first premolar area. The thickness of the cortical plate
      of the inferior wall of the maxillary sinus was thinnest in the first premolar
      area but it was thickest in the second premolar area. The vertical relationship
      between the inferior wall and the roots of the maxillary molars was classified
      into five types. Type I (the inferior wall of the sinus located above the level
      connecting the buccal and lingual root apices) dominated (54.5% in the first
      molar area, 52.4% in the second molar area). The horizontal relationship between
      the inferior wall of the sinus and the root apex was classified into three types.
      Type 2 (the alveolar recess of the inferior wall of the sinus was located between
      the buccal and lingual roots) was most common (80% in the first and second molar
      area). Overall, this study demonstrated the many anatomical characteristics and
      determined the relationships between the maxillary sinus and their surrounding
      structures. These findings may have an impact on the clinical management of
      patients.

PMID- 15145041
TI  - Comparison of the bond strength of selected adhesive dental systems to cortical
      bone under in vitro conditions.
AB  - The study was performed to compare the tensile bond strength attained between
      composite and bone and between bone and bone using two different adhesive systems
      (Clearfil New Bond and Histoacryl) in vitro. Sixty porcine bone specimens with a
      total thickness of 4.0 mm (+/- 0.5 mm) and a cortical layer of 1.5 mm (+/- 0.2
      mm) were obtained under standardised conditions. Ten specimens each were assigned
      to four experimental groups: group A: Clearfil New Bond (bone-composite); group
      B: Clearfil New Bond (bone-bone); group C: Histoacryl (bone-composite); group D:
      Histoacryl (bone-bone). The tensile bond strength of the adhesive agents
      mentioned above was measured 15 min after application and also after light-curing
      of the composite filling material (Tetric Ceram, colour A2; groups A and C) using
      a universal testing machine. The tensile bond strength measured was as follows:
      group A 8.00 MPa (+/- 1.36 MPa), group B 6.39 MPa (+/- 2.05 MPa), group C 5.22
      MPa (+/- 1.96 MPa), and group D 1.95 MPa (+/- 0.49 MPa). Tensile bond strength
      was significantly increased in group A compared to groups C and D (P < 0.05,
      Tukey's test). The values in group D were significantly reduced compared to all
      other groups (P < 0.05, Tukey's test). Despite the limitations of an in vitro
      investigation, it can be concluded that adhesive systems might be a useful
      alternative in bone bonding. The use of dentin adhesives seemed to produce higher
      bond strength to bone than that attained with the cyanoacrylate adhesive.

PMID- 15145043
TI  - Maxillofacial fractures masking traumatic intracranial hemorrhages.
AB  - Maxillofacial trauma may mask intracranial injuries prompting intensive care
      treatment. The purpose of this study was to identify whether craniofacial
      fracture patterns predispose patients with maxillofacial fractures to different
      types of intracranial hemorrhages. Within 7 years, 6649 patients with
      craniomaxillofacial injuries were admitted for treatment. The charts of the
      patients were analyzed according to age, sex, cause and mechanism of injury, type
      and location of facial injury, and intracranial trauma; 2195 sustained
      maxillofacial fractures. Statistical analyses were followed by logistic
      regression analyses for the four main types of intracranial hemorrhage to
      determine the impact of the different maxillofacial fractures. Intracranial
      hemorrhages in 212 patients (9.7%) occurred as epidural (2.5%), subdural (4.3%),
      subarachnoid (5.3%), and intracerebral hemorrhages (6.3%). Le Fort, orbit, nose,
      zygoma, and maxillary fractures increased the risk for accompanying intracranial
      hemorrhage by two- to fourfold (P < 0.05). Basal skull fractures caused a
      multiplication of the risk up to 17-fold, while fractures of the cranial vault
      were associated with a risk up to 14-fold. Nearly 10% of patients with
      craniomaxillofacial fractures sustain intracranial hemorrhages requiring
      frequently immediate neurosurgical intervention. Those patients, suffering from
      central midface fractures and skull base fractures, are prone to highly
      significant elevated risks of intracranial hemorrhage.

PMID- 15145045
TI  - Local primary (AL) amyloidosis in the palate. A case report.
AB  - Oral amyloidosis is usually presented in the tongue and is often regarded as a
      paraneoplastic phenomenon. We present a rare case of primary local amyloidosis in
      the palate of an 80-year-old male. No simultaneous general illnesses or
      malignancies were detected in spite of extensive assessments by specialists in
      internal medicine.

PMID- 15145044
TI  - Total lower lip functional reconstruction with a prefabricated gracilis muscle
      free flap.
AB  - Total lower lip reconstruction was performed in an 18-month-old boy following a
      dog bite. In order to obtain an optimal functional result and to avoid any
      additional facial scarring, a prefabricated gracilis muscle free flap was used in
      a two-stage procedure. Firstly, the muscle was delayed on its main pedicle, a
      'tendinous' strip was inserted along its free border and a silicone sheet was
      slid under its predicted intraoral side. At the time of reconstruction, the
      neomucosal lining obtained in this way reconstituted the labial vestibule.
      Furthermore, the muscle, reinnervated by the mandibular branch of the facial
      nerve, was also put under minimal tension and suspended between the two modioli
      using the 'tendon' graft. This allowed both lip occlusion and normal speech
      development to be restored without any impairment of mandibular growth during a 4
      year follow-up.

PMID- 15145046
TI  - Ectomesenchymal chondromyxoid tumour of the anterior tongue.
AB  - Ectomesenchymal chondromyxoid tumour (ECT) of the anterior tongue was first
      described in 1995. To date, only 23 cases have been reported in the literature.
      Two new cases of ECT have been described, with immunohistochemical analysis
      including cytokeratin (CK) profile, GFAP, S-100 protein, SMA, CD-57, EMA, desmin
      and Ki67. Tumour cells showed intense and diffuse staining for GFAP and diffuse
      staining for S-100 protein. Pan-keratin, high- and low-molecular-weight CK, CK 7,
      8, 18, 19 and 20 were negative. Tumour cells were also negative for desmin, SMA,
      CD-57 and EMA. Ki67 was positive in only scattered cells. The findings of the
      present study support the suggested ectomesenchymal origin for ECT, rather than
      myoepithelial salivary gland origin. The low Ki67 expression is in agreement with
      the low growth rate, small size and lack of mitotic activity in the present
      cases, as well as in those previously described.

PMID- 15145047
TI  - An intraosseous lipoma in the frontal bone--a case report.
AB  - A rare case of a recurrent intraosseous lipoma affecting the frontoparietal skull
      is reported. The diagnostic difficulties, histopathologic features and surgical
      therapy are presented.

PMID- 15145048
TI  - Paediatric necrotizing fasciitis complicating third molar extraction: report of a
      case.
AB  - Necrotizing fasciitis is an uncommon but well-described entity. In the paediatric
      population compromising risk factors are frequently absent. We describe the
      successful treatment of a case of cervicofacial necrotizing fasciitis in a
      healthy 14-year-old male following routine extraction of an uninfected wisdom
      tooth for orthodontic purposes.

PMID- 15145049
TI  - Cap-dependent and cap-independent translation in eukaryotic systems.
AB  - Unlike bacterial protein synthesis, eukaryotic protein synthesis has several
      mechanisms to initiate translation including cap-dependent initiation, re
      initiation and internal initiation. While there is extensive biochemical
      characterization of the multiple steps in cap-dependent initiation, most of the
      information on the other two mechanisms is derived from studies on the nucleic
      acid sequences that influence their efficiency. However, even in the best of
      circumstances, both re-initiation and internal initiation are only 25% as
      efficient as cap-dependent initiation and more commonly, are only 1-10% as
      efficient. This general lack of efficiency leaves open possibilities for mis
      interpretation/artifacts in vivo (cryptic promoters, alternate splicing) or in
      vitro (nuclease degradation). Two examples are cited from the author's laboratory
      as background for the development of a general set of guidelines to minimize
      errors and validate authenticity for internal initiation.

PMID- 15145050
TI  - Secretions of plant-parasitic nematodes: a molecular update.
AB  - The interaction between sedentary endoparasitic nematodes and plants is
      fascinating, because these animals have developed an ingenious way to manipulate
      the plant's gene regulation and metabolism to their own advantage. They are able
      to form highly specialized feeding structures in the plant root to satisfy their
      nutritional demands for development and reproduction. This ability makes them
      extremely successful parasites with severe consequences for agriculture.
      Triggered by these economical losses, detailed studies of the parasitic
      interaction have been performed, which resulted in an extensive descriptive
      knowledge. However, the underlying biochemical and molecular events of this
      intimate relationship have still not been elucidated. It is generally accepted
      that secretions produced by the nematode are responsible for the dramatic
      alteration of specific cells in the host plant. In the past few years, the
      identification of genes coding for secreted proteins was a breakthrough in plant
      nematode research. However, the available information is still too limited to
      allow the formulation of a comprehensive model, mainly because the sequences of
      many of these genes are novel with no similar sequence found in the existing
      databases. A new challenge in the coming years will be the functional analysis of
      these putative parasitism genes.

PMID- 15145051
TI  - Identification of genes expressed in response to phytoplasma infection in leaves
      of Prunus armeniaca by messenger RNA differential display.
AB  - The messenger RNA (mRNA) differential display technique was applied to the
      identification and isolation of genes whose transcription was altered in leaves
      of Prunus armeniaca infected by European stone fruit yellows (ESFY) phytoplasma
      belonging to ribosomal subgroup 16SrX-B. Four genes whose steady-state levels of
      expression significantly changed in response to phytoplasma infection were
      isolated and identified. The results obtained show that two group of genes are
      affected by phytoplasma infection in apricot leaves. The first group comprises
      genes that are up-regulated by phytoplasma presence: in particular, a gene
      encoding the heat-shock protein HSP-70, a gene encoding a metallothionein (MT)
      and another homologous to the EST 673 cDNA clone of P. armeniaca, whose function
      was unknown. The other gene identified in our analysis is down-regulated by
      phytoplasma presence. It encodes a protein having homology to an amino acid
      transporter of Arabidopsis thaliana. Our findings demonstrate the usefulness of
      mRNA differential display approach for the detection of plant metabolic pathways
      affected by phytoplasma infection.

PMID- 15145052
TI  - Characterization and tissue-specific expression of human LRIG2.
AB  - We have recently identified and cloned the human LRIG1 gene (formerly LIG1).
      LRIG1 is a predicted integral membrane protein with a domain organization
      reminiscent of the Drosophila epidermal growth factor (EGF)-receptor antagonist
      Kekkon-1. We have searched for additional members of the human LRIG family and
      identified LRIG2 (). The LRIG2 gene was localized to chromosome 1p13 and had an
      open reading frame of 1065 amino acids. The LRIG2 protein was predicted to have
      the same domain organization as LRIG1 with a signal peptide, an extracellular
      part containing15 leucine-rich repeats and three immunoglobulin-like domains, a
      transmembrane domain, and a cytoplasmic tail. The LRIG2 amino acid sequence was
      47% identical to human LRIG1 and mouse Lrig1 (also known as Lig-1). Northern
      blotting and RT-PCR revealed LRIG2 transcripts in all tissues analyzed.
      Quantitative real-time RT-PCR showed the most prominent RNA expression in skin,
      uterus, ovary, kidney, brain, small intestine, adrenal gland, and stomach.
      Immunoblotting of COS-7 cell lysates demonstrated that heterologously expressed
      human LRIG2 had an apparent molecular weight of 132 kDa under reducing gel
      running conditions. N-glycosidase F treatment resulted in a reduction of the
      apparent molecular weight to 107 kDa, showing that LRIG2 was a glycoprotein
      carrying N-linked oligosaccharides. Cell surface biotinylation experiments and
      confocal fluorescence laser microscopy demonstrated expression of LRIG2 both at
      the cell surface and in the cytoplasm. LRIG2 was detected in tissue lysates from
      stomach, prostate, lung, and fetal brain by immunoblotting. In conclusion, LRIG2
      was found to be a glycoprotein which was encoded by a gene on human chromosome
      1p13 and its mRNA was present in all tissues analyzed.

PMID- 15145053
TI  - Cloning and characterisation of the RBCC728/TRIM36 zinc-binding protein from the
      tumor suppressor gene region at chromosome 5q22.3.
AB  - DNA alterations at chromosome 5q22 occur frequently in different types of tumors
      including urological cancers. Previously, we narrowed a common target region
      between loci D5S659 and D5S2055 at chromosome 5q22.3 by microsatellite
      allelotyping. After constructing a BAC contig and shot-gun sequencing we
      identified a putative exon by the NIX software package. By PCR cloning using the
      putative exon (5qex5) specific primers and primers directed to the vector
      (lambdaZAPII) sequence of human brain and kidney cDNA libraries, we obtained a
      full-length cDNA of 4074 bp of the new gene RBCC728/TRIM36 (GenBank accession
      no.) with an ORF coding for a protein of 728 amino acids. The TRIM36, which is a
      new member of the tripartite motif (TRIM) gene family, shows a RING finger C3HC4
      structure, two B-box, a coiled-coil, a fibronectin type III and a C-terminal
      domain of unknown function (SPRY). The TRIM36 has a weak homology to MID1.
      Immunohistochemistry of recombinant and native TRIM36 displays a cytoplasmic,
      slightly filamentous staining pattern in COS-7 cells. The TRIM36 is expressed in
      adult testis, brain, prostate, kidney, heart and lung. A variable level of TRIM36
      expression was detected by Q-RT-PCR in conventional RCC, while the gene was
      consequently upregulated in PCs. We did not find mutation in the open reading
      frame of the TRIM36 in cancer cells. The overexpression of the TRIM36 in the vast
      majority of prostate cancer suggest that this gene might be involved in the
      prostate tumorigenesis.

PMID- 15145054
TI  - Analysis of gene network regulating yeast multidrug resistance by artificial
      activation of transcription factors: involvement of Pdr3 in salt tolerance.
AB  - We established a strategy to constitutively activate Zn(2)Cys(6)-type protein by
      fusing its DNA-binding domain with the VP16 trans-activation domain. To explore
      gene network regulating yeast multidrug resistance, the strategy was applied to
      Pdr1, Pdr3 and Yrr1, known to regulate multidrug resistance, as well as three
      uncharacterized Yrr1-related transcription factors. DNA microarray analysis
      revealed that all of the six mutants induce typical drug transporter genes
      including SNQ2 and YOR1, suggesting redundancy in regulation. On the other hand,
      each displays a unique spectrum of targets, which is coincident with the
      phylogenetic tree of the transcription factors and presumably reflects their
      functional specification. Indeed, careful analysis of target genes specific to
      each transcription factor led us to reveal an unexpected role for Pdr3 in salt
      tolerance. The strategy would thus contribute not only to identify target genes
      but to reveal redundancy and specificity in complex gene regulatory networks.

PMID- 15145055
TI  - Pigment cell lineage-specific expression activity of the ascidian tyrosinase
      related gene.
AB  - Solitary ascidian tadpole larvae develop two types of black pigment cells in the
      major sensory organs of the brain. Such pigment cells have been demonstrated to
      express the melanogenic genes, tyrosinase and Tyrp/TRP (tyrosinase-related
      protein). To understand the genetic and developmental mechanisms underlying the
      differentiation of chordate pigment cells, we examined the function of the
      promoter region of Tyrp/TRP gene, an ascidian (Halocynthia roretzi) tyrosinase
      family gene. The expression of the gene in pigment cell lineage starts at the
      early-mid gastrula stages. To identify the transcriptional regulatory region of
      the gene allowing cell-type-specific expression, a deletion series of the HrTyrp
      5' flanking region fused to a lacZ reporter gene was constructed and
      microinjected into ascidian fertilized eggs. The region of 73 bp in HrTyrp was
      identified as sufficient for expression in pigment cell-precursors of tailbud
      stage embryos. It is noteworthy that there is no M-box element highly conserved
      in the promoters for vertebrate tyrosinase family genes such as tyrosinase,
      Tyrp1/TRP-1 and Tyrp2/TRP-2 (Dct). Although the regulatory system of ascidian
      pigment-cell development is likely to contain most factors critical to vertebrate
      pigment-cell development, there might be critical differences in the mode of
      regulation, such as the developmental timing of interactions of factors, proteins
      and genes, involved in pigment cell differentiation and pigmentation.

PMID- 15145056
TI  - Large-scale gene rearrangements in the mitochondrial genomes of two calanoid
      copepods Eucalanus bungii and Neocalanus cristatus (Crustacea), with notes on new
      versatile primers for the srRNA and COI genes.
AB  - Partial sequences of the mitochondrial genomes were determined for two calanoid
      copepods, Eucalanus bungii [9530 bp (base pairs)] and Neocalanus cristatus (7965
      bp), using an approach that employs a long polymerase chain reaction (PCR)
      technique and primer walking. In contrast to Tigriopus japonicus (Harpacticoida),
      in which the complete mitochondrial genome has been determined, genes are encoded
      on both strands of the genome. In spite of the close relationship between E.
      bungii and N. cristatus, the gene orders of these calanoid copepods differed
      greatly from each other. From the sequence we obtained, new copepod-specific
      versatile primers were designed for the cytochrome c oxidase I (COI) gene (1200
      bp). These primer pairs, as well as the previously designed primer pairs for the
      small ribosomal RNA (srRNA) gene (500 bp), were applied for 20 species
      representing four orders of both calanoid and non-calanoid copepods and
      amplification of sequences from at least one species from each order was
      successful.

PMID- 15145057
TI  - Duplicated Spot 14 genes in the chicken: characterization and identification of
      polymorphisms associated with abdominal fat traits.
AB  - In mammals, thyroid hormone responsive Spot 14 (THRSP) is a small acidic protein
      that is predominately expressed in lipogenic tissue (i.e., liver, abdominal fat
      and the mammary gland). This gene has been postulated to play a role in
      lipogenesis, since it responds to thyroid hormone stimulation, high glucose
      levels and it is localized to a chromosomal region implicated in obesity. In this
      paper, we report the identification and characterization of duplicated
      polymorphic paralogs of Spot 14 in the chicken, THRSPalpha and THRSPbeta. Despite
      low similarity in amino acid (aa) sequence between chickens and mammals, other
      properties of Spot 14 (i.e., pI, subcellular localization, transcriptional
      control and functional domains) appear to be highly conserved. Furthermore, a
      synteny group of THRSP and its flanking genes [NADH dehydrogenase (NDUFC2) and
      glucosyltransferase (ALG8)] appears to be conserved among chickens, humans, mice
      and rats. Polymorphic alleles, involving a variable number of tandem repeats
      (VNTR), were discovered in the putative protein coding region of the duplicated
      chicken THRSPalpha (9 bp) and THRSPbeta (6 or 12 bp) genes. Our study shows that
      the THRSPalpha locus is associated with abdominal fat traits in a broilerxLeghorn
      resource population.

PMID- 15145058
TI  - Compositional nonrandomness upstream of start codons in archaebacteria.
AB  - Since the regions directing transcriptional and translational initiation in
      archaebacteria are poorly characterized, the purpose of this study was to
      characterize them using measurements of nonrandomness upstream of start codons on
      eight fully sequenced archaebacterial genomes. Two distinctly different regions
      with conservation were identified. The location of the first corresponded well to
      the classical Shine-Dalgarno region (phi peak), and the other was located
      approximately 20-35 nucleotides upstream of start codons (alpha region), but both
      regions are not present in all strains. The composition of the region around the
      phi peak showed an overrepresentation of guanine, whereas composition in the
      alpha region had an overrepresentation of adenine and thymine. It is furthermore
      shown that the alpha region surprisingly is associated with start codon usage and
      other characteristics of the genes. The alpha region is likely to correspond to
      TATA-boxes and thereby indicates use of leaderless (or short-leadered)
      transcripts.

PMID- 15145059
TI  - Isolation, expression and bioactivity of feline granulocyte-macrophage colony
      stimulating factor.
AB  - A cDNA encoding feline granulocyte-macrophage colony stimulating factor was
      cloned from alveolar macrophages using the reverse transcriptase-polymerase chain
      reaction (RT-PCR). The cDNA is 426 bp in length and encodes a predicted mature
      protein of 127 amino acids and the majority of the signal peptide. The
      recombinant protein (rfGM-CSF) was expressed in both Escherichia coli, as a
      calmodulin fusion protein, and mammalian cells. Biological activity of both
      recombinant proteins was demonstrated using the human erythroleukaemic cell line,
      TF-1. In a soft agar clonogenic assay, rfGM-CSF supported the development of
      granulocyte, macrophage and granulocyte-macrophage colonies. In combination with
      phytohaemagglutin (PHA) lymphocyte-conditioned medium, the number and size of
      such colonies were increased. Culture of feline bone marrow cells with rfGM-CSF
      was an efficient method for producing cells with morphology typical of dendritic
      cells (DC). The availability of the recombinant cytokine will permit further
      studies, in particular, the evaluation of the role of dendritic cells in feline
      immunopathology and its potential as a vaccine adjuvant.

PMID- 15145060
TI  - The spectrum of human rhodopsin disease mutations through the lens of
      interspecific variation.
AB  - Mutations in rhodopsin, the visual pigment found in rod cells, account for a
      large fraction of genetic changes underlying the human retinal diseases,
      Retinitis Pigmentosa (RP). The availability of rhodopsin sequences from a large
      number of vertebrates has allowed us to investigate factors important in the
      development of RP by contrasting interspecific differences (long-term
      evolutionary patterns) with RP disease mutation data. We find that disease
      mutations in rhodopsin are overabundant in highly conserved sites and that amino
      acid positions with any potential of variability among vertebrates are likely to
      harbour disease mutations less frequently. At any amino acid position in
      rhodopsin, the set of disease-associated amino acids does not show any
      commonality with the set of amino acids present among species. The disease
      mutations are biochemically four times more radical than the interspecific
      (neutral) variation. This pattern is also observed when disease mutations are
      categorized based on clinical classifications that reflect biochemical,
      physiological and psychophysical traits such as protein folding, cone
      electroretinogram (ERG) amplitude, pattern of visual field loss, and equivalent
      field diameter. We also found that for artificial mutations (those not observed
      in nature interspecifically), there was a positive relationship between the
      biochemical distance and the magnitude of blue shift in the absorption spectrum
      maximum. We introduce the concept of the expected chemical severity based on the
      normal human codon at a position. Results reveal that the analysis of disease
      mutations in the context of the original codon is very important for the
      practical application of evolutionary principles when comparing original and
      disease amino acid mutations. We conclude that the analysis of rhodopsin data
      clearly demonstrates the usefulness of molecular evolutionary analyses for
      understanding patterns of clinical as well as artificial mutations and
      underscores the biomedical insights that can be gained by using simple measures
      of biochemical difference in the context of evolutionary divergence.

PMID- 15145061
TI  - cDNA cloning and characterization of the human THRAP2 gene which maps to
      chromosome 12q24, and its mouse ortholog Thrap2.
AB  - Characterization of a balanced t(2;12)(q37;q24) translocation in a patient with
      suspicion of Noonan syndrome revealed that the chromosome 12 breakpoint lies in
      the vicinity of a novel human gene, thyroid hormone receptor-associated protein 2
      (THRAP2). We therefore characterized this gene and its mouse counterpart in more
      detail. Human and mouse THRAP2/Thrap2 span a genomic region of about 310 and >170
      kilobases (kb), and both contain 31 exons. Corresponding transcripts are
      approximately 9.5 kb long. Their open reading frames code for proteins of 2210
      and 2203 amino acids, which are 93% identical. By northern blot analysis, human
      and mouse THRAP2/Thrap2 genes showed ubiquitous expression. Transcripts were most
      abundant in human skeletal muscle and in mouse heart. THRAP2 protein is 56%
      identical to human TRAP240, which belongs to the thyroid hormone receptor
      associated protein (TRAP) complex and is evolutionary conserved up to yeast. This
      complex is involved in transcriptional regulation and is believed to serve as
      adapting interface between regulatory proteins bound to specific DNA sequences
      and RNA polymerase II.

PMID- 15145062
TI  - DNA replication initiates at domains overlapping with nuclear matrix attachment
      regions in the xenopus and mouse c-myc promoter.
AB  - Only a very few origins have been mapped in different multicellular organisms,
      and they do not share detectable consensus sequence elements. Moreover, it is not
      clear if origins are localized at similar positions in the corresponding locus in
      genomes of different organisms. Here, we have mapped DNA replication origins in
      the c-myc locus both in Xenopus and mouse, allowing a comparison of the
      corresponding sites in three different animal species (Xenopus, mouse, human). An
      origin of DNA replication is present in the three homologous c-myc loci. In
      Xenopus, a main DNA replication origin was located 3 kilobases (kb) upstream of
      the active c-myc promoter, whereas, in mouse, we detected an origin 1 kb upstream
      of the promoter, as previously mapped in human c-myc. We also identified a
      nuclear matrix attachment region in both Xenopus and mouse, which is localized to
      two different regions of the c-myc promoter region. However, in both cases, the
      nuclear matrix attachment sites are close to the DNA replication origin mapped in
      the locus. These data suggest that global features of chromatin organization in
      different organisms may contribute to DNA replication origin localization.

PMID- 15145063
TI  - Chemical footprinting of structural and functional elements of dhfr oribeta
      during the CHOC 400 cell cycle.
AB  - Oribeta, an origin of replication 3' to Chinese hamster dihydrofolate reductase
      (dhfr) gene, contains several sequence elements that function as components of a
      chromosomal replicator. Here we have examined sensitivity to KMnO(4) in vitro and
      in living cells of three regions within dhfr oribeta which contribute to
      replicator function: the origin of bidirectional DNA replication (OBR) that
      serves as an initiation site for DNA synthesis, a stably bent DNA region that
      binds activator protein one (AP-1) and RIP60 in vitro, and an AT-rich region that
      contains a dA/dT(23) dinucleotide repeat that has properties of a DNA unwinding
      element. The in vitro patterns of KMnO(4) modification in linear plasmid differed
      from that in supercoiled plasmid most prominently in the dA/dT(23) repeat, with
      evidence of palindrome extrusion in supercoiled plasmid. Although palindrome
      extrusion was not detected in genomic DNA during the cell cycle, the pattern of
      genomic DNA modification within the dA/dT(23) repeat differed substantially from
      that of either linear or plasmid DNA in vitro. An AT-rich region that borders the
      dA/dT repeat was also highly sensitive to modification by KMnO(4) in cells.
      Within the bent DNA region, the patterns of chemical modification of both the AP
      1 and RIP60 sites differed between plasmid and genomic DNA, and minor differences
      in the in vitro and cellular modification patterns also were observed for the
      OBR. Nonetheless, there was little evidence of cell cycle-specific modifications
      in any sequence examined. These studies suggest that sequences within dhfr
      oribeta adopt specific conformations in cells, with the most prominent changes in
      the AT-rich region associated with the dA/dT(23) repeat and DNA unwinding.

PMID- 15145064
TI  - Identification of a GDP-mannose pyrophosphorylase gene from Sulfolobus
      solfataricus.
AB  - An open reading frame (ORF) encoding a putative GDP-mannose pyrophosphorylase
      (SsoGMPP) was identified on the genome sequence of Sulfolobus solfataricus P2,
      the predicted gene product showing high amino acid sequence homology to several
      archaeal, bacterial, and eukaryal GDP-mannose pyrophosphorylases such as
      guanidine diphosphomannose pyrophosphorylases (GMPPs) from Saccharomyces
      cerevisiae and Arabidopsis thaliana. The sequence was PCR amplified from genomic
      DNA of S. solfataricus P2 and heterologous gene expression obtained as a fusion
      to glutathione S-transferase in Escherichia coli, under conditions suitable to
      reduce the formation of inclusion bodies. Specific assays performed at 60 degrees
      C revealed the presence of the archaeal synthesizing GDP-mannose enzyme activity
      in the cell extracts of the transformed E. coli. As a positive control, the same
      assays were performed at the mesophilic enzyme optimum temperature on the already
      characterized yeast recombinant GMPP. The recombinant protein was purified to
      homogeneity by glutathione sepharose affinity chromatography and its thermophilic
      nature could be verified. The enzyme was definitively identified by demonstrating
      its capability to catalyze also the reverse reaction of pyrophosphorolysis and,
      most interestingly, its high specificity for synthesizing GDP-mannose.

PMID- 15145065
TI  - Evolutionary dynamics of satellite DNA in species of the Genus Formica
      (Hymenoptera, Formicidae).
AB  - The satellite DNA has been characterized in eight species of the Formica genus.
      This satellite DNA is organized as tandemly repeated 129-bp monomers in all
      species and it presents internal inverted repeats. The results of all the
      analyses performed in the sequences sampled from Formica cunicularia, F. fusca,
      F. gerardi, F. rufibarbis, F. selysi, F. frontalis, and F. sanguinea suggest
      interspecific conservation of satellite DNA. Nevertheless, the results from the
      comparative analysis of the sequences sampled from F. subrufa and the remaining
      species studied suggest that the mechanisms producing concerted evolution have
      been efficient in these taxa. A CENP-B-like motif has been found in the satellite
      DNA from the species analysed, including F. subrufa. This satellite DNA is
      located in the pericentromeric regions of all chromosomes. We suggest that,
      although the evolution of the DNA satellite in ants could be similar to that in
      other organisms, there may be some particularities as a result of a haplodiploid
      system.

PMID- 15145066
TI  - Conserved patterns in the evolution of Tribolium satellite DNAs.
AB  - Two satellite DNAs, TANAPH and TDEST, isolated from the beetle species Tribolium
      anaphe and Tribolium destructor, respectively, are characterized and compared
      with previously described Tribolium satellites, in order to deduce possible
      constraints on satellite sequence evolution between closely related species.
      Sequence diversity analysis of cloned monomers reveals the presence of variable
      and conserved segments in both satellites. In addition, non-random organization
      of As or Ts and their periodical distribution in the form of A or T >/=3 tracts,
      as well as CENP-B box-like motifs and dyad structures have been found in both
      satellites. Similar structural features are also present in satellites from other
      Tribolium species. We therefore propose that they, together with the observed non
      constant rate of evolution along the satellite sequence, could be related to
      putative protein binding sites and suggest a possible selective pressure
      affecting these sequences. Tribolium satellites, including TANAPH and TDEST, are
      located in the pericentromeric heterochromatin of all chromosomes of the
      corresponding species. Since satellites from different species exhibit no
      significant sequence homology, we propose that they did not originate from a
      common ancestral sequence. More probably, they derive from simple sequence
      modules some of which could represent protein binding sites. Shuffling of simple
      sequence modules could generate different satellites, able to perform a similar
      role in different species.

PMID- 15145068
TI  - Lobotomy of genes: use of RNA interference in neuroscience.
AB  - Galen of Pergamon studied nerve function by shearing nerves in various species
      including monkeys, dogs, bulls and even elephants (humans being off limits to
      researchers; Sartan, 1954). An analogous strategy to determine gene function by
      ablating gene expression has recently been developed. RNA interference (RNAi) is
      a cellular response to double-stranded RNA (dsRNA) apparently as a defense
      against viral or transposon activity (Denli and Hannon, 2003; Dykxhoorn et al.,
      2003; Plasterk, 2002; Zamore, 2002). By activating this ancient defense mechanism
      through the introduction of artificial dsRNA, it is now possible to inhibit
      expression of almost any gene in almost any cell type, among them neuronal cells.
      In mammalian cells the active RNAi species must be short, approximately 21
      nucleotide RNAs; these 21-bp species are called short interfering RNA (siRNA; Fig
      1).

PMID- 15145067
TI  - Comparative analysis of gene expression mechanisms between group IA and IB
      phospholipase A2 genes from sea snake Laticauda semifasciata.
AB  - Phospholipase A(2) (PLA(2)) genes expressed in the venom glands of the sea snake,
      Laticauda semifasciata, were investigated. Both mRNAs, encoding group IA (without
      a pancreatic loop) and group IB (with pancreatic loop), were detected from venom
      glands by Northern blot hybridization analysis and RT-PCR. The results of
      quantitative PCR analysis indicated that the expression amount of group IA genes
      was around 100-300 times greater than that of group IB genes. Sequence analysis
      of 5'-upstream regions and a reporter gene assay of the genes (groups IA and IB)
      previously cloned showed that the functional sequence (411 bp) was inserted in
      the 5'-flanking region of the group IA PLA(2) genes. It seemed that the
      contribution of the inserted sequence to the amount of transcribed mRNAs was
      greater than that of number of genes present in the genome. Comparative analysis
      of the 5'-flanking sequences from several snake genes encoding toxic PLA(2)s
      revealed that this sequence was probably inserted into an ancestral gene of
      PLA(2) with a pancreatic loop. After the duplication of the gene, which contained
      the inserted sequence, the PLA(2) gene without a pancreatic loop evolved from one
      of the duplicate genes. This inserted sequence might determine the future of the
      genes expressed in the venom glands.

PMID- 15145069
TI  - Does the amygdala modulate adaptation to repeated stress?
AB  - Exposure of the rat to restraint results in activation of the hypothalamic
      pituitary-adrenal (HPA) axis, a characteristic pattern of c-fos expression in the
      brain and increased cardiovascular function. These responses adapt with repeated
      exposure of an individual to the same stress. Corticosterone secretion
      habituates, and c-fos mRNA expression in the paraventricular nucleus of the
      hypothalamus (PVN) decreases. The increased expression of corticotropin releasing
      hormone mRNA in the PVN also becomes less prominent, whereas vasopressin mRNA
      progressively increases. The neural mechanisms responsible for this adaptation
      remain obscure. Because of its role in conditioned learning, we have hypothesised
      that the amygdala might be involved in this adaptive process. Here we show that
      large neurotoxic lesions of the amygdala in male rats do not prevent acute stress
      activation of the HPA axis following 30 min restraint, whilst more discrete
      lesions of the central nucleus actually exacerbate the acute response. Rats with
      large amygdala lesions demonstrate delayed habituation of corticosterone and c
      fos to repeated restraint, an affect not apparent with central nucleus lesions.
      Furthermore we show that neither type of lesion significantly reduced
      tachycardiac responses to single or repeated restraint as measured by telemetry.
      We conclude that the amygdala and the central nucleus are not necessary for HPA
      and cardiovascular activation in response to stress (though the central nucleus
      may modulate it), and that adaptation to repeated stress is only modestly
      dependent upon the amygdala.

PMID- 15145070
TI  - Learning a new behavioral strategy in the shuttle-box increases prefrontal
      dopamine.
AB  - Using microdialysis from medial prefrontal cortex of gerbils during aversive
      auditory conditioning in the shuttle-box we have previously shown a transient
      increase of dopamine efflux correlated with the establishment of avoidance
      behavior. We hypothesized that the acquisition of a new behavioral strategy is
      generally accompanied by this extra prefrontal dopamine release. The present
      experiment aimed at further testing this hypothesis. In a pre-training period in
      the shuttle-box the gerbils acquired an active avoidance response by generalizing
      two different tone signals to a GO-meaning (change of shuttle-box compartment).
      Thereafter, they were subjected in relearning sessions to differentially
      associate the known tone stimuli with GO- and NOGO- (no change of shuttle-box
      compartment) conditions, respectively. The following formation of discrimination
      behavior led to a similar extra dopamine increase as found during establishment
      of the avoidance strategy. This significant enhancement was limited to rapidly
      relearning individuals. Furthermore, the dopamine increase attenuated in these
      animals with increasing performance during the course of the discrimination
      training, similar to the retrieval stage of the avoidance strategy. Therefore,
      the dopamine system seems to be critically involved in the initial formation of
      associations for new behavioral strategies, i.e. learning. We assume that the
      prefrontal dopamine increase during initial learning of the complex
      discrimination behavior indicates an involvement of working memory principles and
      a goal-directed formation of a behavioral strategy.

PMID- 15145071
TI  - Activation of voltage-sensitive sodium channels during oxygen deprivation leads
      to apoptotic neuronal death.
AB  - Sodium (Na(+)) entry into neurons during hypoxia is known to be associated with
      cell death. However, it is not clear whether Na(+) entry causes cell death and by
      what mechanisms this increased Na(+) entry induces death. In this study we used
      cultures of rat neocortical neurons to show that an increase in intracellular
      sodium (Na(i)(+)) through voltage-sensitive sodium channels (VSSCs), during
      hypoxia contributes to apoptosis. Hypoxia increased Na(i)(+) and induced neuronal
      apoptosis, as assessed by electron microscopy, annexin V staining, and terminal
      UDP nick end labeling staining. Reducing Na(+) entry with the VSSC blocker,
      tetrodotoxin (TTX), attenuated apoptotic neuronal death via a reduction in
      caspase-3 activation. Since the attenuation of apoptosis by TTX during hypoxia
      suggested that the activation of VSSCs and Na(+) entry are crucial events in
      hypoxia-induced cell death, we also determined whether the activation of VSSCs
      per se could lead to apoptosis under resting conditions. Increasing Na(+) entry
      with the VSSC activator veratridine also induced neuronal apoptosis and caspase-3
      activation. These data indicate that a) Na(+) entry via VSSCs during hypoxia
      leads to apoptotic cell death which is mediated, in part, by caspase-3 and b)
      activation of VSSCs during oxygen deprivation is a major event by which hypoxia
      induces cell death.

PMID- 15145072
TI  - Postsynaptic depolarisation enhances transmitter release and causes the
      appearance of responses at "silent" synapses in rat hippocampus.
AB  - Recent data indicate that most "silent" synapses in the hippocampus are
      "presynaptically silent" due to low transmitter release rather than
      "postsynaptically silent" due to "latent" receptors of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid type (AMPARs). That synapses bearing only N
      methyl-d-aspartate (NMDAR) receptors do exist is suggested by the decreased
      number of transmission failures during postsynaptic depolarisation and by the
      presence of NMDA-mediated excitatory postsynaptic currents (EPSCs) in synapses
      silent at rest. We tested whether these effects could be due to potentiated
      transmitter release at depolarised postsynaptic potentials rather than removal of
      Mg(2+) block from NMDARs. Using whole-cell recordings of minimal EPSCs from CA1
      and CA3 neurones of hippocampal slices we confirmed decreased incidence of
      failures at +40 mV as compared with -60 mV. This effect was associated with a
      gradual increase of EPSC amplitude after switching to +40 mV and with a decrease
      of paired-pulse facilitation. In initially silent synapses, potentiation of
      pharmacologically isolated AMPAR-mediated EPSCs was still observed at +40 mV and
      this persisted after stepping back to -60 mV. All above effects were blocked when
      the cell was dialysed with the Ca(2+) chelator BAPTA (20 mM). These observations
      are difficult to reconcile with the "latent AMPAR" hypothesis and suggest an
      alternative explanation, namely that the reduction in failure rates at positive
      potentials is due to potentiation of transmitter release following Ca(2+) influx
      through NMDARs. Our results suggest that silent synapses can be mainly
      "presynaptically" rather than "postsynaptically silent" and thus increased
      transmitter release rather than insertion of AMPARs is a major mechanism of early
      long-term potentiation maintenance.

PMID- 15145073
TI  - Modulation of Na(+),K(+) pumping and neurotransmitter uptake by beta-amyloid.
AB  - Micromolar concentrations of beta-amyloid (Abeta), a 40/42-amino-acid-long
      proteolytic fragment (Abeta(1-40/42)) of the amyloid precursor protein, was shown
      previously to play a crucial role in pathogenesis of Alzheimer's disease. We used
      the Xenopus oocyte expression system to investigate specific effects of
      micromolar concentrations of Abeta(1-42) on the neurotransmitter transporters for
      gamma-aminobutyric acid (GABA), GAT1, and for the excitatory amino acid
      glutamate, EAAC1, which are driven by the transmembrane Na(+) gradient that is
      regulated by the Na(+),K(+)-ATPase. Brief treatment with Abeta(1-42), up to 80
      min, leads to a significant inhibition of ion translocation by the Na(+),K(+)
      ATPase (30-40%); also glutamate uptake is inhibited (20%) while GABA uptake is
      not affected. Since reduced glutamate uptake will result in elevated, neurotoxic
      concentrations of extracellular glutamate, we investigated the effects of Abeta(1
      42) and the smaller fragments, Abeta(12-28) and Abeta(25-35), on EAAC1 in more
      detail. Prolonged incubation in 1 microM Abeta(1-42) leads to further, strong
      inhibition of glutamate uptake and EAAC1-mediated current (after 4 h inhibition
      amounts to more than 80%). Abeta(12-28) is less effective with 50% inhibition
      after 4 h of incubation at 20 microM. Abeta(1-42) and Abeta(12-28) affect EAAC1
      mediated current to a similar extent as the rate of glutamate uptake. The effects
      on EAAC1-mediated current are irreversible if Abeta were applied for longer time
      periods. Peptides directly microinjected into the oocyte are ineffective
      suggesting that the observed effect were mediated by extracellular proteins.
      Abeta(25-35) hardly affects EAAC1-mediated current or glutamate uptake. The
      results demonstrate that Abeta specifically inhibits the Na(+),K(+) pump and
      EAAC1. The domain between amino acids 12 and 28 of Abeta seems to play a crucial
      role for inhibition of EAAC1. The inhibition of EAAC1 by neurotoxic, elevated
      extracellular glutamate levels may contribute to Alzheimer's pathogenesis.

PMID- 15145074
TI  - Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial
      cells and mechanism of PAR-1-induced calcium signaling.
AB  - Protease-activated receptors (PARs) are a group of four members of the
      superfamily of G protein-coupled receptors that transduce cell signaling by
      proteolytic activity of extracellular serine proteases, such as thrombin.
      Possible expression and functions of PARs in oligodendrocytes, the myelin forming
      cells of the CNS, are still unclear. Here, the oligodendrocyte cell line OLN-93
      was used to investigate the signaling of PARs. By reverse transcription
      polymerase chain reaction (RT-PCR), immunostaining and Ca(2+) imaging studies, we
      demonstrate that OLN-93 cells functionally express PAR-1. PAR-3 seems to be
      expressed without apparent activity, and PAR-2 and PAR-4 cannot be detected.
      Short-term stimulation of the OLN-93 cells with PAR-1 agonists, such as thrombin,
      trypsin and PAR-1 activating peptide, dose-dependently induced a transient rise
      of [Ca(2+)](i). Concentration-effect curves display a sigmoidal concentration
      dependence. Elevation of [Ca(2+)](i) induced by PAR-1 mainly resulted from Ca(2+)
      release from intracellular stores. Studies on the effects of pertussis toxin
      (PTX), phospholipase C antagonist and 2-APB, showed that in OLN-93 cells (i). the
      calcium signaling cascade from PAR-1 was mediated through PTX-insensitive G
      proteins, (ii). activation of phospholipase C and liberation of InsP(3) were
      events upstream of the Ca(2+) release from the stores. In addition, the present
      study analyzed PAR-1 desensitization caused by exposure to thrombin, trypsin, and
      PAR-1 activating peptide, elucidated the influence of the protease cathepsin G on
      PAR-1 activation, and also characterized PAR-1 desensitization. This is the first
      study, which shows that OLN-93 oligodendrocytes functionally express PAR-1, and
      identifies the receptor coupling to mobilization of intracellular calcium.
      Moreover, the expression of PAR-1 was demonstrated by RT-PCR in primary
      oligodendrocytes from rat brain.

PMID- 15145075
TI  - Subthreshold contribution of N-methyl-d-aspartate receptors to long-term
      potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal
      cells.
AB  - Long-term potentiation (LTP) is a use-dependent and persistent enhancement of
      synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian
      characteristics and requires precisely timed interaction between presynaptic
      firing and postsynaptic depolarization. Although depolarization is an absolute
      requirement for plasticity, it is still not clear whether the postsynaptic
      response during LTP induction should be subthreshold or suprathreshold for the
      generation of somatic action potential. Here, we use the whole-cell patch-clamp
      technique and different pairing protocols to examine systematically the
      postsynaptic induction requirements for LTP. We induce LTP by changes only in
      membrane potential while keeping the afferent stimulation constant and at minimal
      levels. This approach permits differentiation of two types of LTP: LTP induced
      with suprathreshold synaptic responses (LTP(AP)) and LTP induced with
      subthreshold excitatory postsynaptic current (EPSCs; LTP(EPSC)). We found that
      LTP(AP) (>40%) required pairing of depolarization (V(m)>or=-40 mV, for 40-60 s)
      with four to six (0.1 Hz) single synaptically initiated action potentials.
      LTP(EPSC) was of smaller magnitude (<30%) and required pairing of depolarization
      to -50 mV (60 s) with six subthreshold EPSCs. The N-methyl-d-aspartate receptor
      (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid
      consistently blocked LTP(EPSC) but were ineffective in preventing LTP(AP).
      Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization
      that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR
      dependent LTP is obtained by pairing mild somatic depolarization with
      subthreshold afferent pulses to the postsynaptic cell. Our results indicate that
      the degree of postsynaptic depolarization in the presence of single afferent
      pulses determines the type and magnitude of LTP.

PMID- 15145076
TI  - ATP-induced inhibition of gap junctional communication is enhanced by interleukin
      1 beta treatment in cultured astrocytes.
AB  - Nucleotides are signaling molecules involved in variety of interactions between
      neurons, between glial cells as well as between neurons and glial cells. In
      addition, ATP and other nucleotides are massively released following brain
      insults, including inflammation, and may thereby be involved in mechanisms of
      cerebral injury. Recent concepts have shown that in astrocytes intercellular
      communication through gap junctions may play an important role in
      neuroprotection. Therefore, we have studied the effects of nucleotides on gap
      junction communication in astrocytes. Based on measurement of intercellular dye
      coupling and recording of junctional currents, the present study shows that ATP
      (10-100 microM) induces a rapid and a concentration-dependent inhibition of gap
      junction communication in cultured cortical astrocytes from newborn mice. Effects
      of agonists and antagonists of purinergic receptors indicate that the inhibition
      of gap junctional communication by ATP mainly involves the stimulation of
      metabotropic purinergic 1 (P2Y(1)) receptors. Pretreatment with the pro
      inflammatory cytokine interleukin-1beta (10 ng/ml, 24 h), which has no effect by
      itself on gap junctional communication, increases the inhibitory effect of ATP
      and astrocytes become sensitive to uridine 5'-triphosphate (UTP). As indicated by
      the enhanced expression of P2Y(2) receptor mRNA, P2Y(2) receptors are responsible
      for the increased responses evoked by ATP and UTP in interleukin-1beta-treated
      cells. In addition, the effect of endothelin-1, a well-known inhibitor of gap
      junctional communication in astrocytes was also exacerbated following interleukin
      1beta treatment. We conclude that ATP decreases intercellular communication
      through gap junctions in astrocytes and that the increased sensitivity of gap
      junction channels to nucleotides and endothelin-1 is a characteristic feature of
      astrocytes exposed to pro-inflammatory treatments.

PMID- 15145077
TI  - AMPA receptor alterations precede mossy fiber sprouting in young children with
      temporal lobe epilepsy.
AB  - Following neurological injury early in life numerous events, including
      excitotoxicity, neural degeneration, gliosis, neosynaptogenesis, and circuitry
      reorganization, may alone or in concert contribute to hyperexcitability and
      recurrent seizures in temporal lobe epilepsy. Our studies provide new evidence
      regarding the temporal sequence of key elements of hippocampal reorganization,
      mossy fiber sprouting and glutamate receptor subunit up-regulation, in a subset
      of young temporal lobe epileptic patients. Without evidence of mossy fiber
      sprouting, the youngest age group (3-10 years old) of mesial temporal lobe
      epileptic patients demonstrated enhanced glutamate receptor subunit profiles,
      suggesting that the dendritic change precedes axonal sprouting. However,
      sclerotic hippocampal specimens from epileptic patients ages 12-15 years old had
      the characteristic features of glutamate receptor up-regulation and mossy fiber
      sprouting first identified in the adult, indicating that reconstructed circuits
      appear early in the course of the disease. Non-sclerotic hippocampal specimens
      from lesion associated temporal lobe epileptic patients of all age groups showed
      minimal cell loss, sparse staining of glutamate receptor subunits in the dentate
      gyrus, and little or no mossy fiber sprouting. These compelling findings suggest
      a progressive sequence of events in the reorganization of the dentate gyrus of
      sclerotic hippocampal specimens. We suggest that cell loss and up-regulation of
      glutamate receptor subunits appear early in temporal lobe epilepsy and contribute
      to the synaptic plasticity that may facilitate the subsequent sprouting of mossy
      fiber collaterals which compound an already precipitous state of decline. The
      combination of pre-synaptic and post-synaptic changes serves as a potential
      substrate for hyperexcitability.

PMID- 15145078
TI  - Quantification of synapse formation and maintenance in vivo in the absence of
      synaptic release.
AB  - Outgrowing axons in the developing nervous system secrete neurotransmitters and
      neuromodulatory substances, which is considered to stimulate synaptogenesis.
      However, some synapses develop independent of presynaptic secretion. To
      investigate the role of secretion in synapse formation and maintenance in vivo,
      we quantified synapses and their morphology in the neocortical marginal zone of
      munc18-1 deficient mice which lack both evoked and spontaneous secretion [Science
      287 (2000) 864]. Histochemical analyses at embryonic day 18 (E18) showed that the
      overall organization of the neocortex and the number of cells were similar in
      mutants and controls. Western blot analysis revealed equal concentrations of pre-
      and post-synaptic marker proteins in mutants and controls and immunocytochemical
      analyses indicated that these markers were targeted to the neuropil of the
      synaptic layer in the mutant neocortex. Electron microscopy revealed that at E16
      immature synapses had formed both in mutants and controls. These synapses had a
      similar synapse diameter, active zone length and contained similar amounts of
      synaptic vesicles, which were immuno-positive for two synaptic vesicle markers.
      However, these synapses were three times less abundant in the mutant. Two days
      later, E18, synapses in the controls had more total and docked vesicles, but not
      in the mutant. Furthermore, synapses were now five times less abundant in the
      mutant. In both mutant and controls, synapse-like structures were observed with
      irregular shaped vesicles on both sides of the synaptic cleft. These
      'multivesicular structures' were immuno-positive for synaptic vesicle markers and
      were four times more abundant in the mutant. We conclude that in the absence of
      presynaptic secretion immature synapses with a normal morphology form, but fewer
      in number. These secretion-deficient synapses might fail to mature and instead
      give rise to multivesicular structures. These two observations suggest that
      secretion of neurotransmitters and neuromodulatory substances is required for
      synapse maintenance, not for synaptogenesis. Multivesicular structures may
      develop out of unstable synapses.

PMID- 15145079
TI  - Kynurenate in the pontine reticular formation inhibits acoustic and trigeminal
      nucleus-evoked startle, but not vestibular nucleus-evoked startle.
AB  - The startle reflex is elicited by acoustic, trigeminal or vestibular stimulation,
      or by combinations of these stimuli. Acoustic startle is mediated largely by
      ibotenate-sensitive neurons in the ventrocaudal pontine reticular formation
      (PnC). In these studies we tested whether startle elicited by stimulation of
      different modalities is affected by infusion of the non-selective glutamate
      antagonist, kynurenate, into the PnC. In awake rats, startle responses evoked by
      either acoustic or spinal trigeminal nucleus stimulation were inhibited by
      kynurenate, but not saline, infusions, with the most effective placements nearest
      PnC. In chloral hydrate-anesthetized rats, kynurenate in the PnC reduced
      trigeminal nucleus-evoked hindlimb EMG responses, but not vestibular nucleus
      evoked startle. Kynurenate in the vestibular nucleus had no effect on trigeminal
      nucleus-evoked startle. These results indicate that trigeminal nucleus
      stimulation evokes startle largely through glutamate receptors in the PnC,
      similarly to acoustic startle, but vestibular nucleus-evoked startle is mediated
      through other pathways, such as the vestibulospinal tract.

PMID- 15145080
TI  - Neurokinin-1 and -3 receptor blockade inhibits slow excitatory synaptic
      transmission in myenteric neurons and reveals slow inhibitory input.
AB  - Recent studies have shown that tachykinins mediate slow synaptic transmission to
      myenteric AH (afterhyperpolarising) neurons via neurokinin-3 receptors (NK(3)R).
      This study investigated a similar role for neurokinin-1 receptors (NK(1)R) and
      compared the effect of selective receptor antagonists on non-cholinergic slow
      excitatory post-synaptic potentials (EPSPs) recorded in myenteric AH neurons of
      the guinea-pig ileum. Slow EPSPs evoked by electrical stimulation of
      circumferentially oriented presynaptic nerves were mimicked by application of
      senktide, an NK(3)R agonist. [Sar(9),Met(O(2))(11)]-substance P, an NK(1)R
      agonist, depolarised a smaller number of neurons. SR142801, a selective NK(3)R
      antagonist (100 nM), inhibited slow EPSPs and responses to senktide, but had no
      effect on depolarisations evoked by forskolin, an activator of adenylate cyclase.
      SR140333, a selective NK(1)R antagonist, inhibited slow EPSPs in a subset of
      neurons and blocked responses to [Sar(9),Met(O(2))(11)]-substance P, but not to
      senktide or forskolin. Slow EPSPs that were predominantly mediated by NK(1)R had
      significantly shorter latencies than those due to activation of NK(3)R. After
      blockade of slow EPSPs, slow hyperpolarizing responses to presynaptic nerve
      stimulation were revealed in one-third of neurons. These events, which were
      associated with a decrease in input resistance and blocked by tetrodotoxin, were
      equated with slow inhibitory postsynaptic potentials. They were abolished by the
      5-hydroxytryptamine(1A) receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]-piperazine (NAN-190), but unaffected by phentolamine, an alpha
      adrenoceptor antagonist. In conclusion, these results provide the first direct
      evidence that NK(1)R mediate some slow excitatory synaptic input to myenteric AH
      neurons, and suggest that NK(1)R and NK(3)R activate distinct signal transduction
      pathways. These results also demonstrate that slow inhibitory synaptic
      transmission, which may be mediated by 5-hydroxytryptamine, is more prevalent in
      the myenteric plexus than previously indicated.

PMID- 15145082
TI  - Hyperexcitability induced by GABA withdrawal facilitates hippocampal long-term
      potentiation.
AB  - In some mammals, epileptic seizures have been induced in the cerebral cortex,
      hippocampus and other limbic structures after the sudden suppression of
      chronically infused GABA. This hyperexcitability state induced by the endogenous
      neurotransmitter resembles the withdrawal seizure-responses to other GABA(A)
      receptor agonists such as benzodiazepines, barbiturates and alcohol.
      Hyperexcitability induced by GABA withdrawal also persists in in vitro
      preparation. Hippocampal slices, obtained from rats with seizures induced by GABA
      withdrawal showed field potential oscillations and paroxysmal activity in the
      Ammon's horn region 1. During GABA-withdrawal hyperexcitability the threshold of
      hippocampal long-term potentiation (LTP) decreased to a point in which a brief
      frequency stimulation that normally failed to produce long lasting changes in
      synaptic strength, was now able to induce LTP. Facilitation of the LTP induction
      was associated with a decreased GABA(A)-mediated inhibitory activity, because the
      effect of the GABA(A) receptor antagonist, bicuculline, was occluded during
      hyperexcitability and the dose-response curve for bicuculline showed a 50%
      efficacy reduction with a shift in the effective concentration required for half
      maximal activation from 4.5-1.1 microM relative to controls. Nevertheless, the
      dissociation constant of the antagonist did not change significantly. Our results
      support the idea that changes in hippocampal plasticity under altered inhibitory
      neurotransmission states, like those induced by withdrawal syndromes to
      anxiolytic, sedative or anticonvulsant drugs may be engaged during seizures.

PMID- 15145081
TI  - Ethanol inhibits brain-derived neurotrophic factor-mediated intracellular
      signaling and activator protein-1 activation in cerebellar granule neurons.
AB  - Developmental exposure to ethanol causes profound damage to the cerebellum,
      ranging from aberration in neuronal differentiation to cell loss. As a major
      neurotrophic factor, brain-derived neurotrophic factor (BDNF) and its receptor
      TrkB are expressed in the developing, as well as adult, cerebellum. Many
      neurotrophic effects of BDNF are mediated by gene transcription. We hypothesized
      that ethanol interfered with BDNF signaling and disrupted BDNF-regulated
      transcriptional activity. Using a transgenic mouse model expressing an activator
      protein-1 (AP-1) luciferase reporter construct, we demonstrated that BDNF
      stimulated AP-1 transactivation in cultured cerebellar granule neurons. This
      observation was validated by the study using a human neuronal cell line
      expressing inducible TrkB (TB8 neuroblastoma cells). BDNF induced AP-1
      transactivation, as well as increased the binding activity of AP-1 protein
      complex to a DNA sequence containing AP-1 sites in TB8 cells. BDNF-mediated AP-1
      activation was mediated by PI3K/Akt and JNK pathways; BDNF activated Akt and
      JNKs, and blocking these pathways significantly inhibited BDNF-stimulated AP-1
      transactivation. More importantly, ethanol inhibited BDNF-mediated activation of
      PI3K/Akt and JNKs, and blocked BDNF-stimulated AP-1 activation. Since ethanol did
      not affect either the expression or autophosphorylation of TrkB, it could be
      concluded that the site of ethanol action was downstream of TrkB. The present
      study establishes that this AP-1 reporter transgenic mouse model is valuable for
      assessing AP-1 activity in the CNS neurons. Our results provide an insight into
      molecular mechanism(s) of ethanol action.

PMID- 15145083
TI  - The effects of treatment with antibodies to transforming growth factor beta1 and
      beta2 following spinal cord damage in the adult rat.
AB  - We recently showed axonal ingrowth into fibronectin (FN) mats implanted into the
      spinal cord. However, little axonal growth was found from FN mats into intact
      spinal cord. Previous research has shown that this is due in part to astrocytosis
      around an area of CNS damage. Antibodies to transforming growth factor beta
      (TGFbeta) can diminish this astrocytosis. TGFbeta also has effects on macrophages
      and Schwann cells, both of which infiltrate the spinal cord following damage. We
      examined the axonal, Schwann cell, and macrophage infiltration into FN mats as
      well as the level of astrocytosis and chondroitin sulfate proteoglycan NG2 around
      FN implants incubated in TGFbeta antibodies and implanted into a lesion cavity in
      the spinal cord. We also examined the effects of applying TGFbeta antibodies to a
      spinal cord hemisection site. Anti-TGFbeta1 within FN mats resulted in extensive
      cavitation, with the area of damage being larger than the original lesion.
      Cavitation was also seen following application of anti-TGFbeta1 to a spinal cord
      hemisection site. No cavitation was seen following saline, non-immune IgG or anti
      TGFbeta2 treatment. However, anti-TGFbeta2 treatment did result in diminished
      axonal growth and Schwann cell and macrophage infiltration. Around the implant
      site, anti-TGFbeta2 treatment resulted in a reduction in the level of
      astrocytosis but had not effect on levels of NG2. Similar effects were seen
      following anti-TGFbeta2 application to spinal cord hemisection sites. The results
      suggest that anti-TGFbeta1 exacerbates secondary damage by preventing the anti
      inflammatory effect of endogenous TGFbeta1. Anti-TGFbeta2 did not enhance axonal
      regeneration in this model but did slightly reduce astrocytosis.

PMID- 15145084
TI  - N-methyl-d-aspartate receptor activation exerts a dual control on postnatal
      development of nucleus tractus solitarii neurons in vivo.
AB  - We have used a morphological approach to evaluate the role of NMDA receptors
      (NMDAR) in postnatal development of brainstem neurons in awake rats. Chronic
      NMDAR blockade was performed by placing drug-impregnated Elvax implants over the
      brainstem at the fifth postnatal day (P5). Compared with control, NMDAR blockade
      led to a transient increase in dendritic arbor area and filopodium density until
      P12 followed by a rapid decline in both parameters. Electron microscopy
      observations showed that these changes correlated with an increase in synapse
      density at P14 followed by a decrease in synapse density at P28 if chronic NMDAR
      blockade was maintained until P21. These results support the hypothesis that
      synapse formation does not require NMDAR activation. In addition, our data
      suggest a dual role for NMDAR in controlling the synapse number. Early in
      development NMDARs may be involved in controlling the rate of synapse
      elimination. Later on, they may subserve synapse stabilization. The physiological
      significance of these results is discussed.

PMID- 15145085
TI  - Purinergic synapses formed between rat sensory neurons in primary culture.
AB  - Though there is some evidence to the contrary, dogma claims that primary sensory
      neurons in the dorsal root ganglion do not interact, that the ganglion serves as
      a through-station in which no signal processing occurs. Here we use patch clamp
      and immunocytochemistry to show that sensory neurons in primary culture can form
      chemical synapses on each other. The resulting neurotransmitter release is
      calcium dependent and uses synaptotagmin-containing vesicles. On many cells
      studied, the postsynaptic receptor for the neurotransmitter is a P2X receptor, an
      ion channel activated by extracellular ATP. This shows that sensory neurons have
      the machinery to form purinergic synapses on each other and that they do so when
      placed in short-term tissue culture.

PMID- 15145086
TI  - Cortical convergence from different frequency domains in the cat primary auditory
      cortex.
AB  - Primary auditory cortex (AI) has a tonotopic map consisting of orderly
      isofrequency (IF) bands, and cortical connections are commonly supposed to link
      domains preferring similar characteristic frequencies (CFs) within AI and in
      auditory association cortex. The interaction of different frequency channels,
      however, has not fully been understood in terms of anatomical substrates. Here,
      by injecting two anterograde tracers in different frequency domains of cat AI,
      without overlap of the injection cores, we attempted to relate the anatomical
      mapping of cortical outputs to physiologically defined fields in the auditory
      cortex. Consistent with previous studies, patches of labeled axon terminals were
      oriented largely along the IF axis. In regions distant from the injection sites,
      however, terminal patches were divergent in distribution. This divergence
      resulted in a complex geometry of partial overlap of projections originating from
      the two injection sites. The relative extent of the overlap tended to vary
      depending on the distance between the two injection sites. Physiological mapping
      for tonotopy across auditory fields revealed that projectional overlap was
      characteristic of dorsal AI and the dorsoposterior field and, to a lesser extent,
      in the secondary auditory field. Considering the differences in frequency
      representation in different AI IF bands, the anatomical convergence of
      projections tuned to different CFs could contribute to the spectral integration
      of sound components. Furthermore, the different extent of convergence in the
      functionally distinct fields might reflect field-specific processing of acoustic
      signals.

PMID- 15145087
TI  - Imaging parallel fiber and climbing fiber responses and their short-term
      interactions in the mouse cerebellar cortex in vivo.
AB  - A major question in the study of cerebellar cortical function is how parallel
      fiber and climbing fiber inputs interact to shape information processing.
      Emphasis has been placed on the long-term effects due to conjunctive stimulation
      of climbing fibers and parallel fibers. Much less emphasis has been placed on
      short-term interactions and their spatial nature. To address this question the
      responses to parallel fiber and climbing fiber inputs and their short-term
      interaction were characterized using optical imaging with Neutral Red in the
      anesthetized mouse in vivo. Electrical stimulation of the cerebellar surface
      evoked an increase in fluorescence consisting of a transverse optical beam. The
      linear relationship between the optical responses and stimulus parameters, high
      spatial resolution and close coupling to the electrophysiological recordings show
      the utility of this imaging methodology. The majority of the optical response was
      due to activation of postsynaptic alpha-amino-3-hydroxyl-5-methyl-4-isoxazole
      propionate (AMPA) and metabotropic glutamate receptors with a minor contribution
      from the presynaptic parallel fibers. Stimulation of the inferior olive evoked
      parasagittal bands that were abolished by blocking AMPA glutamate receptors.
      Conjunctive stimulation of the cerebellar surface and inferior olive resulted in
      inhibition of the climbing fiber evoked optical responses. This lateral
      inhibition of the parasagittal bands extended out from both sides of an activated
      parallel fiber beam and was mediated by GABA(A) but not GABA(B) receptors. One
      hypothesized role for lateral inhibition of this type is to spatially focus the
      interactions between parallel fiber and climbing fiber input on Purkinje cells.
      In summary optical imaging with Neutral Red permitted visualization of cerebellar
      cortical responses to parallel fiber and climbing fiber activation. The GABA(A)
      dependent lateral inhibition of the climbing fiber evoked parasagittal bands by
      parallel fiber stimulation shows that cerebellar interneurons play a short-term
      role in shaping the responses of Purkinje cells to climbing fiber input.

PMID- 15145088
TI  - Medullary pathways mediating specific sympathetic responses to activation of
      dorsomedial hypothalamus.
AB  - We sought to determine which medullary sympathetic premotor neurons mediate the
      cardiovascular and thermogenic effects resulting from activation of neurons in
      the dorsomedial hypothalamus (DMH) in urethane/chloralose-anesthetized,
      artificially ventilated rats. Unilateral disinhibition of neurons in the DMH with
      microinjection of bicuculline (2 mM, 30 nl) caused significant increases in brown
      adipose tissue sympathetic nerve activity (BAT SNA, +828+/-169% of control,
      n=16), cardiac SNA (+516+/-82% of control, n=16), renal SNA (RSNA, +203+/-25% of
      control, n=28) and, accompanied by increases in BAT temperature (+1.6+/-0.3
      degrees C, n=11), end-tidal CO(2) (+0.7+/-0.1%, n=15), heart rate (+113+/-7
      beats/min, n=32), arterial pressure (+19+/-2 mm Hg, n=32) and plasma epinephrine
      and norepinephrine concentrations. Inhibition of neurons in the rostral raphe
      pallidus (RPa) with microinjection of muscimol (6 mM, 60 nl) abolished the
      increases in BAT SNA and BAT temperature and reduced the tachycardia induced by
      disinhibition of DMH neurons. Inhibition of neurons in the RVLM with
      microinjection of muscimol (6 mM, 60 nl) markedly reduced the increase in RSNA,
      but did not affect the evoked tachycardia or the increase in arterial pressure.
      Combined glutamic acid decarboxylase (GAD-67) immunocytochemistry and
      pseudorabies viral retrograde tracing from BAT indicated close appositions
      between GABAergic terminals and DMH neurons in sympathetic pathways to BAT. In
      conclusion, these results demonstrate the existence of a tonically active,
      GABAergic inhibitory input to neurons in the DMH and that blockade of this
      inhibition increases sympathetic outflow to thermogenic and cardiovascular
      targets by activating functionally specific populations of sympathetic premotor
      neurons: the excitation of BAT SNA and BAT thermogenesis is mediated through
      putative sympathetic premotor neurons in the RPa, while the activation in RSNA is
      dependent on those in RVLM. These data increase our understanding of the central
      pathways mediating changes in sympathetically mediated thermogenesis that is
      activated in thermoregulation, stress responses and energy balance.

PMID- 15145089
TI  - Chronic cortisol suppresses pituitary and hypothalamic peptide message expression
      in pigtailed macaques.
AB  - The effects of chronic elevations in circulating glucocorticoids on the
      expression of peptides and peptide receptors of the hypothalamic-pituitary
      adrenal (HPA) axis have been studied extensively in rodents, but they have not
      been examined in primates. To determine the responses of the HPA axis in primates
      to elevated cortisol, hypothalamic and pituitary tissue from normal older
      pigtailed macaques (Macaca nemestrina) that had received daily oral
      administration of cortisol or placebo for 1 year were studied. Pro
      opiomelanocortin in the anterior pituitary and corticotropin-releasing factor
      (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN) were
      significantly reduced in cortisol-treated monkeys in comparison with controls.
      CRF receptor 1 (CRF-R1) expression in the anterior pituitary and arginine
      vasopressin mRNA expression in the PVN were unchanged by chronic cortisol
      administration. Sustained elevation of circulating glucocorticoids results in
      suppression of HPA peptide and peptide receptor expression in the PVN and
      anterior pituitary similar to those found in rodents. Chronic therapeutic
      administration of glucocorticoids in humans may have unintended consequences for
      hypothalamic and pituitary function.

PMID- 15145090
TI  - Ischemic heart disease in women: facts and wishful thinking.

PMID- 15145091
TI  - The pathophysiology of cigarette smoking and cardiovascular disease: an update.
AB  - Cigarette smoking (CS) continues to be a major health hazard, and it contributes
      significantly to cardiovascular morbidity and mortality. Cigarette smoking
      impacts all phases of atherosclerosis from endothelial dysfunction to acute
      clinical events, the latter being largely thrombotic. Both active and passive
      (environmental) cigarette smoke exposure predispose to cardiovascular events.
      Whether there is a distinct direct dose-dependent correlation between cigarette
      smoke exposure and risk is debatable, as some recent experimental clinical
      studies have shown a non-linear relation to cigarette smoke exposure. The exact
      toxic components of cigarette smoke and the mechanisms involved in CS-related
      cardiovascular dysfunction are largely unknown, but CS increases inflammation,
      thrombosis, and oxidation of low-density lipoprotein cholesterol. Recent
      experimental and clinical data support the hypothesis that cigarette smoke
      exposure increases oxidative stress as a potential mechanism for initiating
      cardiovascular dysfunction.

PMID- 15145092
TI  - From knowledge to practice in chronic cardiovascular disease: a long and winding
      road.
AB  - Although clinical practices evolve over time, the translation of specific
      research evidence into clinical practice is unpredictable, inconsistent, and
      complex. In this paper, we use examples from chronic cardiovascular conditions
      to: 1). highlight two types of care gaps; 2). describe the most common potential
      barriers to the application of evidence into clinical care; and 3). outline which
      of the strategies for translating evidence into clinical care have been shown to
      be ineffective, which strategies have been shown to be effective and to describe
      some untested approaches that hold promise.

PMID- 15145094
TI  - Surgery, angioplasty, or medical therapy for symptomatic multivessel coronary
      artery disease: is there an indisputable "winning strategy" from evidence-based
      clinical trials?

PMID- 15145093
TI  - The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled
      clinical trial of three therapeutic strategies for multivessel coronary artery
      disease: one-year results.
AB  - OBJECTIVES: We sought to evaluate the relative efficacies of three possible
      therapeutic strategies for patients with multivessel coronary artery disease
      (CAD), stable angina, and preserved ventricular function. BACKGROUND: Despite
      routine use of coronary artery bypass graft surgery (CABG) and percutaneous
      coronary intervention (PCI), there is no conclusive evidence that either one is
      superior to medical therapy (MT) alone for the treatment of multivessel CAD.
      METHODS: The primary end point was defined as cardiac mortality, Q-wave
      myocardial infarction (MI), or refractory angina requiring revascularization. All
      data were analyzed according to the intention-to-treat principle. RESULTS: A
      total of 611 patients were randomly assigned to either a CABG (n = 203), PCI (n =
      205), or MT (n = 203) group. The one-year survival rates were 96.0% for CABG,
      95.6% for PCI, and 98.5% for MT. The rates for one-year survival free of Q-wave
      MI were 98% for CABG, 92% for PCI, and 97% for MT. After one-year follow-up, 8.3%
      of MT patients and 13.3% of PCI patients underwent to additional interventions,
      compared with only 0.5% of CABG patients. At one-year follow-up, 88% of the
      patients in the CABG group, 79% in the PCI group, and 46% in the MT group were
      free of angina (p < 0.0001). CONCLUSIONS: Medical therapy for multivessel CAD was
      associated with a lower incidence of short-term events and a reduced need for
      additional revascularization, compared with PCI. In addition, CABG was superior
      to MT for eliminating anginal symptoms. All three therapeutic regimens yielded
      relatively low rates of cardiac-related deaths.

PMID- 15145096
TI  - Does hospital coronary intervention volume matter in predicting mortality?

PMID- 15145095
TI  - Hospital percutaneous coronary intervention volume and patient mortality, 1998 to
      2000: does the evidence support current procedure volume minimums?
AB  - OBJECTIVES: The aim of this study was to evaluate current American College of
      Cardiology/American Heart Association (ACC/AHA) hospital percutaneous coronary
      intervention (PCI) volume minimum recommendations. BACKGROUND: In order to reduce
      procedure-associated mortality, ACC/AHA guidelines recommend that hospitals
      offering PCIs perform at least 400 PCIs annually. It is unclear whether this
      volume standard applies to current practice. METHODS: We conducted a
      retrospective analysis of the Agency for Healthcare Research and Quality's
      Nationwide In-patient Sample hospital discharge database to evaluate in-hospital
      mortality among patients (n = 362748) who underwent PCI between 1998 and 2000 at
      low (5 to 199 cases/year), medium (200 to 399 cases/year), high (400 to 999
      cases/year), and very high (1000 cases or more/year) PCI volume hospitals.
      RESULTS: Crude in-hospital mortality rates were 2.56% in low-volume hospitals,
      1.83% in medium-volume hospitals, 1.64% in high-volume hospitals, and 1.36% in
      very high-volume hospitals (p < 0.001 for trend). Compared with patients treated
      in high-volume hospitals (odds ratio [OR] 1.00, referent), patients treated in
      low-volume hospitals remained at increased risk for mortality after adjustment
      for patient characteristics (OR 1.21, 95% confidence interval [CI] 1.06 to 1.28).
      However, patients treated in medium-volume hospitals (OR 1.02, 95% CI 0.92 to
      1.14) and patients treated in very high-volume hospitals (OR 0.94, 95% CI 0.85 to
      1.03) had a comparable risk of mortality. Findings were similar when high- and
      very high-volume hospitals were pooled together. CONCLUSIONS: We found no
      evidence of higher in-hospital mortality in patients undergoing PCI at medium
      volume hospitals compared with patients treated at hospitals with annual PCI
      volumes of 400 cases of more, suggesting current ACC/AHA PCI hospital volume
      minimums may merit reevaluation.

PMID- 15145097
TI  - Sustained ventricular tachycardia or fibrillation in the cardiac catheterization
      laboratory among patients receiving primary percutaneous coronary intervention:
      incidence, predictors, and outcomes.
AB  - OBJECTIVES: We sought to evaluate the incidence, predictors, and outcomes of
      ventricular tachycardia and/or ventricular fibrillation (VT/VF) in the cardiac
      catheterization laboratory among patients undergoing primary percutaneous
      coronary intervention (PCI). BACKGROUND: Although VT/VF has been known to occur
      during primary PCI, the current data do not identify patients at risk for these
      arrhythmias or the outcomes of such patients. METHODS: We evaluated 3065 patients
      enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI) trials, who
      underwent primary PCI to evaluate the associations of VT/VF and the influence of
      these arrhythmias on in-hospital and one-year outcomes. RESULTS: In patients
      undergoing primary PCI, VT/VF occurred in 133 (4.3%). Multivariate analysis
      identified the following as independent correlates of VT/VF: smoking (odds ratio
      [OR] 1.95, 95% confidence interval [CI] 1.26 to 3.02), lack of preprocedural beta
      blockers (OR 2.34, 95% CI 1.35 to 4.07), time from symptom onset to emergency
      room of <or=180 min (OR 2.63, 95% CI 1.42 to 4.89), initial Thrombolysis In
      Myocardial Infarction (TIMI) flow grade 0 (OR 2.06, 95% CI 1.23 to 3.47), and
      right coronary artery-related infarct (OR 1.93, 95% CI 1.25 to 2.99). Although
      patients with VT/VF had a higher incidence of bradyarrhythmias, hypotension,
      cardiopulmonary resuscitation, and endotracheal intubation in the catheterization
      laboratory, their in-hospital and one-year adverse outcomes were similar to those
      of the cohort without these arrhythmias. CONCLUSIONS: Our findings suggest that
      the incidence of VT/VF during primary PCI is low, indicating that these
      arrhythmias do not influence PCI success or in-hospital or one-year outcomes. Our
      data further help identify patients at risk of VT/VF during primary PCI and
      suggest that pretreatment with beta-blockers should be strongly considered to
      reduce these arrhythmias.

PMID- 15145098
TI  - Does beta-blocker therapy improve clinical outcomes of acute myocardial
      infarction after successful primary angioplasty?
AB  - OBJECTIVES: We sought to determine if beta-blocker therapy improves clinical
      outcomes of acute myocardial infarction (AMI) after successful primary
      percutaneous coronary intervention (PCI). BACKGROUND: We have shown that pre
      treatment with beta-blockers has a beneficial effect on short-term clinical
      outcomes in patients undergoing primary PCI for AMI. It is unknown if beta
      blocker therapy after successful primary PCI improves prognosis of AMI. METHODS:
      We analyzed clinical, angiographic, and outcomes data in 2442 patients who
      underwent successful primary PCI in the Primary Angioplasty in Acute Myocardial
      Infarction-2 (PAMI-2), PAMI No Surgery-on-Site (PAMI noSOS), Stent PAMI, and Air
      PAMI trials. We classified patients into beta group (those who received beta
      blockers after successful PCI, n = 1661) and no-beta group (n = 781). We compared
      death and major adverse cardiac events (MACE) (death, reinfarction, and ischemia
      driven target vessel revascularization) at six months between groups receiving
      and not receiving beta-blockers. RESULTS: At six months, beta patients were less
      likely to die (2.2% vs. 6.6%, p < 0.0001) or experience MACE (14 vs. 17%, p =
      0.036). In multivariate analysis, beta-blockers were independently associated
      with lower six-month mortality (odds ratio [OR] 0.43, 95% confidence interval
      [CI] 0.26 to 0.73, p = 0.0016). Beta-blocker therapy was an independent predictor
      of lower six-month events in high-risk subgroups: ejection fraction <or=50%
      (death: OR 0.34, 95% CI 0.19 to 0.60, p = 0.0002) or multi-vessel coronary artery
      disease (CAD) (death: OR 0.26, 95% CI 0.14 to 0.48, p < 0.0001; MACE: OR 0.57,
      95% CI 0.41 to 0.80, p = 0.0011). CONCLUSIONS: Treatment with beta-blockers after
      successful primary PCI is associated with reduced six-month mortality, with the
      greatest benefit in patients with a low ejection fraction or multi-vessel CAD.

PMID- 15145099
TI  - Impact of intravenous beta-blockade before primary angioplasty on survival in
      patients undergoing mechanical reperfusion therapy for acute myocardial
      infarction.
AB  - OBJECTIVES: We sought to examine the effect of intravenous beta-blockers
      administered before primary percutaneous coronary intervention (PCI) on survival
      and myocardial recovery after acute myocardial infarction (AMI). BACKGROUND:
      Studies of primary PCI but not thrombolysis have suggested that beta-blocker
      administration before reperfusion may enhance survival. Whether oral beta-blocker
      use before admission modulates this effect is unknown. METHODS: The Controlled
      Abciximab and Device Investigation to Lower Late Angioplasty Complications
      (CADILLAC) trial randomized 2082 AMI patients to either stenting or balloon
      angioplasty, each +/- abciximab. In accordance with the protocol, intravenous
      beta-blockers were administered before PCI in the absence of contraindications.
      RESULTS: A total of 1136 patients (54.5%, BB+ group) received beta-blockers
      before PCI, whereas 946 (45.5%, BB- group) did not. The 30-day mortality was
      significantly lower in the BB+ group than in the BB- group (1.5% vs. 2.8%, p =
      0.03), an effect entirely limited to patients who had not been receiving beta
      blockers before admission (1.2% vs. 2.9%, p = 0.007). In contrast, no survival
      benefit with pre-procedural beta-blockers was observed in patients receiving beta
      blockers at home (3.3% vs. 1.9%, respectively, p = 0.47). By multivariate
      analysis, pre-procedural beta-blocker use was an independent predictor of lower
      30-day mortality among patients without previous beta-blocker therapy (relative
      risk = 0.38 [95% confidence interval 0.17 to 0.87], p = 0.02). The improvement in
      left ventricular ejection fraction from baseline to seven months was also greater
      after intravenous beta-blockers (3.8% vs. 1.3%, p = 0.01), an effect limited to
      patients not receiving oral beta-blockers before admission. CONCLUSIONS: In
      patients with AMI undergoing primary PCI, myocardial recovery is enhanced and 30
      day mortality is reduced with pre-procedural intravenous beta-blockade, effects
      confined to patients untreated with oral beta-blocker medication before
      admission.

PMID- 15145100
TI  - Beta-blocker therapy and primary angioplasty: what is the controversy?

PMID- 15145101
TI  - The distribution of 10-Year risk for coronary heart disease among US adults:
      findings from the National Health and Nutrition Examination Survey III.
AB  - OBJECTIVES: We sought to establish the distribution of the 10-year risk for
      coronary heart disease (CHD) among U.S. adults. BACKGROUND: Risk assessment for
      CHD was developed to provide clinicians with a tool to estimate the absolute risk
      of developing CHD. More recently, risk assessment is increasingly being
      incorporated into guidelines for diagnostic testing and treatment. Yet, little is
      known about the 10-year risk distribution for CHD among adults in the U.S. based
      on these risk assessment tools. METHODS: We applied the risk prediction algorithm
      used by the National Cholesterol Education Program Adult Treatment Panel III
      guidelines to data from 13769 participants (representing 157366716 U.S. adults)
      age 20 to 79 years in the Third National Health and Nutrition Examination Survey
      (1988 to 1994). RESULTS: Among participants without self-reported CHD (heart
      attack and angina pectoris), stroke, peripheral vascular disease, and diabetes,
      81.7% (140 million adults) had a 10-year risk for CHD of <10%, 15.5% (23 million
      adults) of 10% to 20%, and 2.9% (4 million adults) of >20%. The proportion of the
      participants with a 10-year risk for CHD of >20% increased with advancing age and
      was higher among men than among women but varied little with race or ethnicity.
      CONCLUSIONS: Our results help to define the distribution of 10-year risk for CHD
      among U.S. adults.

PMID- 15145102
TI  - Implications of estimating coronary heart disease risk in the US population.

PMID- 15145103
TI  - Myocardial contrast echocardiography with a new calibration method can estimate
      myocardial viability in patients with myocardial infarction.
AB  - OBJECTIVES: We have developed a novel calibration technique applicable for
      myocardial contrast echocardiography (MCE). We assessed the value of this
      technique in the recognition of myocardial infarction (MI) and its spatial
      extent, and we also performed a validation study in normal subjects. BACKGROUND:
      The heterogeneity of contrast intensity (CI) among myocardial segments limits the
      clinical use of MCE. METHODS: We performed MCE with a slow-bolus injection of
      Levovist and recorded end-systolic harmonic power Doppler images at intervals of
      four heart beats in 15 normal volunteers and 30 patients with MI. We divided the
      left ventricular (LV) wall into 12 segments and placed the region of interest in
      the subendocardial region in each segment and in the adjacent LV cavity. We
      measured calibrated CI (dB) by subtracting the cavity CI from myocardial CI.
      RESULTS: The mean intersegmental difference in myocardial CI was 15.8 dB at
      baseline, whereas it was reduced to 6.3 dB after calibration (p < 0.01).
      Calibrated CI was higher in the kinetic segments than in the akinetic segments (
      14.5 +/- 2.3 dB [range -18.7 to -9.9 dB] vs. -22.5 +/- 2.6 dB [-27.8 to -17.7
      dB], p < 0.001), and -18.0 dB was the optimal cutoff point to discriminate these
      from each other. Color-coded mapping of calibrated CI may identify the spatial
      extent of persistently akinetic myocardium as areas of calibrated CI of <or=-18.0
      dB. CONCLUSIONS: This new calibration method reduces the intersegmental
      difference in CI in normal subjects. Calibrated CI provides an estimate of
      persistently akinetic myocardium in patients with MI, and its color-coded mapping
      is comprehensive and identifies the spatial extent of MI.

PMID- 15145104
TI  - Incremental value of parametric quantitative assessment of myocardial perfusion
      by triggered Low-Power myocardial contrast echocardiography.
AB  - OBJECTIVES: The purpose of this study was to compare the assessment of myocardial
      perfusion by myocardial parametric quantification (MPQ) with technetium-99m
      sestamibi single-photon emission computed tomographic (SPECT) imaging in humans.
      BACKGROUND: Accurate visual interpretation of myocardial contrast
      echocardiographic (MCE) images is qualitative and requires considerable
      experience. Current computer-assisted quantitative perfusion protocols are
      tedious and lack spatial resolution. Myocardial parametric quantification is a
      novel method that quantifies, color encodes, and displays perfusion data as a set
      of myocardial parametric images according to the relative degree of perfusion.
      METHODS: Forty-six consecutive patients underwent prospective stress/rest
      technetium-99m sestamibi gated-SPECT imaging and MCE using intravenous Optison or
      Definity. Apical two- and four-chamber cine loops at rest and after dipyridamole
      (0.56 mg/kg) stress were acquired. For each patient, the following assessments of
      myocardial perfusion were performed: 1). visual cine-loop assessment (VIS); 2).
      MPQ assessment; and 3). combined VIS + MPQ assessment. RESULTS: The segmental
      rates of agreement for myocardial perfusion with SPECT were 83%, 89%, and 92%
      (kappa = 0.46, 0.58, and 0.68) for VIS, MPQ, and VIS + MPQ, respectively. Similar
      trends were seen for the classification of the presence or absence of a moderate
      to severe perfusion defect, with the agreement for VIS, MPQ, and VIS + MPQ being
      92%, 97%, and 97%, respectively. CONCLUSIONS: Myocardial parametric
      quantification demonstrates good agreement with SPECT and incremental agreement
      with VIS. Analysis strategies that incorporate MPQ demonstrate better agreement
      with SPECT than visual analysis alone.

PMID- 15145105
TI  - Placing faith in numbers: quantification of perfusion with myocardial contrast
      echocardiography.

PMID- 15145106
TI  - Prognostic value of the metabolic syndrome in essential hypertension.
AB  - OBJECTIVES: We sought to determine the prognostic significance of the metabolic
      syndrome in hypertension. BACKGROUND: Increased cardiovascular risk in
      hypertensive patients might be partially attributable to metabolic disturbances.
      METHODS: We prospectively followed for up to 10.5 years (mean 4.1 years) a total
      of 1742 hypertensive patients without cardiovascular disease (55% men; blood
      pressure [BP] 154/95 mm Hg; age 50 +/- 12 years). A modified National Cholesterol
      Education Program definition for metabolic syndrome was used, with body mass
      index in place of waist circumference. RESULTS: During follow-up, 162 patients
      developed cardiovascular events (2.28 events/100 patient-years). Event rates in
      the groups with one to five characteristics of the metabolic syndrome were 1.54,
      1.96, 2.97, 3.35, and 5.27 per 100 patient-years, respectively (p < 0.001). A
      total of 593 patients (34%) had the metabolic syndrome. Patients with the
      syndrome had an almost double cardiovascular event rate than those without (3.23
      vs. 1.76 per 100 patient-years, p < 0.001). After adjustment for age, gender,
      total cholesterol, creatinine, smoking, left ventricular hypertrophy, and 24-h
      systolic BP, the risk of developing cardiovascular events was still higher in
      patients with the metabolic syndrome (hazard ratio [HR] 1.73, 95% confidence
      interval [CI] 1.25 to 2.38). The syndrome was an independent predictor of both
      cardiac and cerebrovascular events (HRs 1.48 and 2.11, respectively). The adverse
      prognostic value of the metabolic syndrome was attenuated but still significant
      among the 1637 patients without diabetes (HR 1.43, 95% CI 1.02 to 2.08).
      CONCLUSIONS: In hypertensive subjects, the metabolic syndrome amplifies
      cardiovascular risk associated with high BP, independent of the effect of several
      traditional cardiovascular risk factors.

PMID- 15145107
TI  - Exercise training normalizes vascular dysfunction and improves central adiposity
      in obese adolescents.
AB  - OBJECTIVES: We sought to characterize the impact of obesity on vascular function
      in adolescents and to determine whether an exercise program reverses
      abnormalities in endothelial function. BACKGROUND: Obesity, a major modifiable
      risk factor for cardiovascular disease, is epidemic in Western societies, with
      rapid rates of increase in the young. Atherosclerosis begins in childhood, and
      endothelial dysfunction is its earliest detectable manifestation. METHODS: The
      influence of eight weeks of circuit training (CT) was examined in 19 obese
      subjects (14.3 +/- 1.5 years), using a randomized, crossover protocol. Functional
      capacity and muscular strength were assessed by standard techniques. Body
      composition was examined using anthropometric measures and dual-energy X-ray
      absorptiometry. Conduit vessel endothelial function was assessed using high
      resolution ultrasound and flow-mediated dilation (FMD) of the brachial artery.
      RESULTS: Circuit training decreased abdominal and trunk fat and significantly
      improved fitness and muscular strength (p < 0.05). In the obese group, FMD was
      significantly impaired relative to control subjects (n = 20) at entry (5.3 +/-
      0.9% vs. 8.9 +/- 1.5%, p < 0.05) and was normalized after CT (8.8 +/- 0.8%, p <
      0.05). CONCLUSIONS: Circuit training improved functional capacity, muscular
      strength, and body composition in obese adolescents. Furthermore, conduit vessel
      function was normalized after exercise training. If vascular dysfunction is an
      integral component of the pathogenesis of vascular disease, this study supports
      the value of an exercise program in the management of obese adolescents.

PMID- 15145108
TI  - High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with
      endothelial dysfunction in a multiethnic cohort.
AB  - OBJECTIVES: This study sought to determine the effect of lipoprotein(a), or
      Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and
      to explore ethnic differences in their effects. BACKGROUND: Although high levels
      of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians,
      its significance in non-Caucasian populations is uncertain. The pathogenic role
      of the apo(a) component of Lp(a) is also unclear. METHODS: The relationship of
      Lp(a) levels and apo(a) sizes to endothelial function was examined in a
      multiethnic cohort of 89 healthy subjects (age 42 +/- 9 years; 50 men, 39 women)
      free of other cardiac risk factors. Endothelium-dependent, flow-mediated dilation
      (FMD) and endothelium-independent, nitrate-induced dilation (NTG) were assessed
      by ultrasound imaging of the brachial artery. RESULTS: Plasma Lp(a) levels were
      lowest in Caucasians (18.3 +/- 21.1 mg/dl, n = 40); intermediate in Hispanics
      (30.2 +/- 30.5 mg/dl, n = 21); and highest in African Americans (68.8 +/- 46.0
      mg/dl, n = 28). Lipoprotein(a) levels were found to correlate inversely to FMD (r
      = -0.33, p < 0.005) but not to NTG (r = 0.06, p = 0.60). This association
      remained significant after adjusting for gender (p = 0.002). In addition,
      subjects with small apo(a) size of <or=22 kringle 4 repeats had significantly
      lower FMD than those with large apo(a) (2.23 +/- 2.37% vs. 6.26 +/- 4.29%, p <
      0.0001), irrespective of Lp(a) levels. CONCLUSIONS: These findings support an
      independent role of Lp(a) in atherogenesis, an effect that is particularly
      evident in African Americans. The proatherogenic property of Lp(a) can be
      attributed in part to its apo(a) component.

PMID- 15145109
TI  - Endocardial and epicardial radiofrequency ablation of ventricular tachycardia
      associated with dilated cardiomyopathy: the importance of low-voltage scars.
AB  - OBJECTIVES: The purpose of this study was to evaluate the occurrence, locations,
      and relationship of ventricular tachycardia (VT) to low-voltage areas in dilated
      cardiomyopathy (DCM). BACKGROUND: The substrate causing monomorphic VT after
      infarction is characterized by regions of low-voltage (<1.5 mV) scar on
      electroanatomic maps. The substrate causing VT associated with DCM is less well
      defined. METHODS: A total of 28 patients were studied with endocardial (26
      patients) and epicardial (8 patients) electroanatomic mapping. The VT circuits
      were defined by entrainment or pace mapping. RESULTS: Ventricular tachycardia was
      due to focal VT in 5, bundle-branch re-entry in 2, and myocardial re-entry in 22
      patients (both focal and re-entry VTs in 1 patient). All patients with myocardial
      re-entry had endocardial (20 of 20 patients) and/or epicardial (7 of 7 patients
      mapped) scar. Most (63%) endocardial scars were adjacent to a valve annulus. Of
      the 19 VT circuit isthmuses identified, 12 were associated with an endocardial
      scar and 7 with an epicardial scar. All myocardial re-entrant VTs were abolished
      in 12 of 22 patients, and inducible VT was modified in 4 patients. During follow
      up of 334 +/- 280 days, 54% of patients with myocardial re-entry were free of VT
      despite frequent episodes before ablation. CONCLUSIONS: The VTs in DCM are most
      commonly the result of myocardial re-entry associated with scar. Scars are often
      adjacent to a valve annulus, deep in the endocardium, and can be greater in
      extent on the epicardium than on the endocardium. The use of epicardial mapping
      and radiofrequency is likely to improve success.

PMID- 15145110
TI  - Implantable cardioverter-defibrillators in patients with arrhythmogenic right
      ventricular dysplasia/cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to assess the outcome of arrhythmogenic
      right ventricular dysplasia/cardiomyopathy (ARVD/C) patients treated with an
      implantable cardioverter-defibrillator (ICD). BACKGROUND: Arrhythmogenic right
      ventricular dysplasia/cardiomyopathy is associated with tachyarrhythmia and an
      increased risk of sudden death. METHODS: This study included 42 ARVD/C patients
      with ICDs (52% male, age 6 to 69 years, median 37 years) followed at our center.
      RESULTS: Mean follow-up was 42 +/- 26 months (range 4 to 135 months).
      Complications associated with ICD implantation included need for lead
      repositioning (n = 3) and system infection (n = 2). During follow-up, one patient
      died of a brain malignancy and one had heart transplantation. Lead replacement
      was required in six patients as a result of lead fracture and insulation damage
      (n = 4) or change in thresholds (n = 2). During this period, 33 of 42 (78%)
      patients received a median of 4 (range 1 to 75) appropriate ICD interventions.
      The median period between ICD implantation and the first firing was 9 months
      (range 0.1 to 66 months). The ICD firing storms were observed in five patients.
      Inappropriate interventions were seen in 10 patients. Predictors of appropriate
      firing were induction of ventricular tachycardia (VT) during electrophysiologic
      study (EPS) (84% vs. 44%, p = 0.024), detection of spontaneous VT (70% vs. 15%, p
      = 0.001), male versus female gender (91% vs. 65%, p = 0.04), and severe right
      ventricular dilation (39% vs. 0%, p = 0.013). Using multivariate analysis, VT
      induction during EPS was associated with increased risk for firing in ARVD/C
      patients; odds ratio 11.2 (95% confidence interval 1.23 to 101.24, p = 0.031).
      CONCLUSIONS: Patients with ARVD/C have a high arrhythmia rate requiring
      appropriate ICD interventions. The ICD therapy appears to be well tolerated and
      important in the management of patients with ARVD/C.

PMID- 15145111
TI  - Hydroquinidine therapy in Brugada syndrome.
AB  - OBJECTIVES: We sought to assess hydroquinidine (HQ) efficacy in selected patients
      with Brugada syndrome (BrS). BACKGROUND: Management of asymptomatic patients with
      BrS and inducible arrhythmias remains a key issue. Effectiveness of class Ia
      antiarrhythmic drugs, which inhibit the potassium transient outward current of
      the action potential, has been suggested in BrS. METHODS: From a cohort of 106
      BrS patients, we studied 35 who received HQ (32 men; mean age 48 +/- 11 years).
      Patients had asymptomatic BrS and inducible arrhythmia (n = 31) or multiple
      appropriate shocks from an implantable cardioverter-defibrillator (ICD) (n = 4).
      Asymptomatic patients with inducible arrhythmia underwent electrophysiologic (EP)
      guided therapy. When ventricular tachycardia (VT)/ventricular fibrillation (VF)
      inducibility was not prevented, or in case of HQ intolerance, an ICD was placed.
      RESULTS: Hydroquinidine prevented VT/VF inducibility in 76% of asymptomatic
      patients who underwent EP-guided therapy. Syncope occurred in two of the 21
      patients who received long-term (17 +/- 13 months) HQ therapy (1 syncope
      associated with QT interval prolongation and 1 unexplained syncope associated
      with probable noncompliance). In asymptomatic patients who received an ICD (n =
      10), one appropriate shock occurred during a follow-up period of 13 +/- 8 months.
      In patients with multiple ICD shocks, HQ prevented VT/VF recurrence in all cases
      during a mean follow-up of 14 +/- 8 months. CONCLUSIONS: Hydroquinidine therapy
      prevented VT/VF inducibility in 76% of asymptomatic patients with BrS and
      inducible arrhythmia, as well as VT/VF recurrence in all BrS patients with
      multiple ICD shocks. These preliminary data suggest that preventive treatment by
      HQ may be an alternative strategy to ICD placement in asymptomatic patients with
      BrS and inducible arrhythmia.

PMID- 15145112
TI  - Left atrial thrombus associated with ablation for atrial fibrillation:
      identification with intracardiac echocardiography.
AB  - OBJECTIVES: This study reports the incidence of, risk factors for, and management
      of left atrial (LA) thrombus documented by intracardiac echocardiography (ICE)
      during LA ablation for atrial fibrillation (AF). BACKGROUND: Thrombus formation
      is a risk associated with LA ablation procedures. METHODS: Intracardiac
      echocardiography imaging was performed in 232 patients (184 men, average age 55
      +/- 11 years) with AF undergoing pulmonary vein ostial ablation. RESULTS:
      Anticoagulation (activated clotting time >250 s) was maintained after dual
      transseptal catheterization. Left atrial thrombus (n = 30) was observed in 24 of
      232 patients (10.3%). Thrombi measured 12.9 +/- 11.1 mm (length) and 2.2 +/- 1.3
      mm (width) and were attached to a sheath or mapping catheter. Most thrombi (27 of
      30, 90%) were eliminated from the LA by withdrawal of the sheath and catheter
      into the right atrium (RA). Two thrombi became wedged in the interatrial septum
      and incompletely withdrawn into the RA, and one was recognized only on post
      procedure review of ICE images. Patients with LA thrombus had an increased LA
      diameter (4.8 +/- 0.5 vs. 4.5 +/- 0.6 cm, p < 0.02), spontaneous echo contrast
      (67% vs. 3%, p < 0.0001) and a history of persistent AF (29% vs. 6%, p < 0.0002).
      Multivariate discriminant analysis showed that spontaneous echo contrast (f =
      97.9, p < 0.0001) was the most important determinant of LA thrombus formation. No
      patient with LA thrombus suffered a clinical thromboembolic complication.
      CONCLUSIONS: Left atrial thrombus identified on ICE may occur during LA catheter
      ablation procedures despite aggressive anticoagulation. Spontaneous echo contrast
      may predict risk for LA thrombus formation. Left atrial thrombus may be
      successfully withdrawn into the RA under ICE imaging with no overt complications.

PMID- 15145113
TI  - Left atrial structure and function after percutaneous left atrial appendage
      transcatheter occlusion (PLAATO): six-month echocardiographic follow-up.
AB  - OBJECTIVES: This study was designed to evaluate the effects of percutaneous left
      atrial appendage transcatheter occlusion (PLAATO) on the anatomic and hemodynamic
      properties of the mitral valve (MV) and left upper pulmonary vein (LUPV).
      BACKGROUND: PLAATO is a device designed to seal the neck of the left atrial (LA)
      appendage and reduce embolization in patients with atrial fibrillation intolerant
      of warfarin. The impact of deployment of this device on adjacent structures has
      not been reported. METHODS: Patients with atrial fibrillation participating in
      the ongoing study for evaluation of PLAATO were enrolled. Transesophageal
      echocardiographies at baseline, one, and six months were reviewed to measure LA
      and LUPV dimensions, degree of mitral regurgitation, stability of the device,
      peak MV E-wave velocity, and peak systolic and diastolic flow velocities in the
      LUPV. Data were analyzed by a linear mixed model for repeated measures. RESULTS:
      Eleven patients (mean age of 72 +/- 7 years) completed six months of follow-up.
      Left upper pulmonary vein diameter (mean: 1.55, 1.61, 1.54 cm, p = 0.13) and peak
      systolic (mean: 0.38, 0.34, 0.31 m/s, p = 0.72) and diastolic flow velocities
      (mean: 0.39, 0.40, 0.42 m/s, p = 0.46) did not differ over the follow-up period.
      Left atrial size, mitral regurgitation severity, and MV peak E-wave velocities
      (mean: 0.94, 0.94, 0.82 m/s, p = 0.58) showed no significant change from
      baseline. The devices remained stable at their sites of deployment with minimal
      residual flow around them. CONCLUSIONS: PLAATO achieved an adequate seal of the
      neck of the left atrial appendage without significant effect on the structure or
      function of the LA and LUPV.

PMID- 15145114
TI  - Utility of B-type natriuretic peptide in predicting postoperative complications
      and outcomes in patients undergoing heart surgery.
AB  - OBJECTIVES: The purpose of the present study was to assess whether preoperative
      and postoperative B-type natriuretic peptide (BNP) levels could be used as
      predictors of postoperative complications and outcomes in patients after open
      heart surgery. BACKGROUND: A variety of multifactor indexes have been proposed
      for preoperative risk assessment of patients undergoing cardiac surgery, but they
      have shown limited ability and utility in accurately predicting postoperative
      complications, hospital stay, and mortality. METHODS: Subjects consisted of 98
      male patients (63 +/- 9.1 years) undergoing open-heart surgery at the San Diego
      Veterans Administration Health System during a 19-month period. B-type
      natriuretic peptide levels were analyzed, and postoperative data recorded.
      RESULTS: There was a higher preoperative BNP level in patients requiring the use
      of intra-aortic balloon pumps (IABPs) (mean BNP = 387 +/- 112 pg/ml vs. 181 +/-
      25 pg/ml), in patients who died within one year (357 +/- 93 pg/ml vs. 184 +/- 26
      pg/ml), and in patients with postoperative hospital stays of 10 days or more (307
      +/- 68 pg/ml vs. 179 +/- 27 pg/ml). Receiver operating characteristic curves
      demonstrated preoperative BNP levels as predictors of postoperative IABP use,
      hospital stay <or=10 days, and mortality <1 year with areas under the curve of
      0.70, 0.64, and 0.70, respectively. A BNP cut-off value above 385 pg/ml
      demonstrated high specificity (=90% in each) and accuracy (=86%, 79%, 85%,
      respectively) for predicting each of these end points. CONCLUSIONS: Preoperative
      BNP levels >385 pg/ml predict the postoperative complications and one-year
      mortality after heart surgery. Postoperatively, elevated peak BNP levels and
      elevated change to peak BNP levels were associated with prolonged hospital stay
      and mortality within one year.

PMID- 15145117
TI  - Lessons from cardiopulmonary testing after device closure of secundum atrial
      septal defects: a tale of two ventricles.

PMID- 15145116
TI  - Determinants of cardiopulmonary functional improvement after transcatheter atrial
      septal defect closure in asymptomatic adults.
AB  - OBJECTIVES: We sought to evaluate the course of cardiopulmonary function after
      transcatheter atrial septal defect (ASD) closure and to identify the
      physiopathologic mechanisms leading to this change. BACKGROUND: Conflicting
      reports exist on cardiopulmonary functional improvement in asymptomatic adults
      after transcatheter closure of a secundum ASD. METHODS: Thirty-two consecutive
      adults (13 males; age 42.6 +/- 16.7 years) underwent maximal cardiopulmonary
      exercise testing and transthoracic echocardiography both on the day before and
      six months after transcatheter ASD closure. Mean pulmonary artery pressure,
      pulmonary to systemic flow ratio (Qp/Qs), and ASD diameter were measured before
      closure. RESULTS: Peak oxygen uptake (Vo(2)) (p < 0.001), peak oxygen pulse (p =
      0.0027), and vital capacity (p = 0.0086) improved after ASD closure, although
      peak heart rate did not. A significant correlation was found between peak Vo(2)
      improvements and Qp/Qs (p = 0.0013). Left ventricular ejection fraction (LVEF) (p
      < 0.0001) and left ventricular end-diastolic diameter (LVEDD) (p < 0.0001)
      significantly increased after six months, although left ventricular end-systolic
      diameter did not. Right ventricular long- and short-axis dimensions decreased
      (both p < 0.0001). Peak Vo(2) and of peak oxygen pulse improvements correlated to
      both LVEF (p = 0.0009 and 0.0019, respectively) and LVEDD (p < 0.0001 and 0.032,
      respectively) increments. The decrease of both long- and short-axis right
      ventricular dimensions positively correlated to both LVEF and LVEDD improvements.
      The improvement in LVEF correlated to Qp/Qs (p = 0.0026). CONCLUSIONS:
      Transcatheter ASD closure leads to a significant improvement in cardiopulmonary
      function within six months, via an increase in peak oxygen pulse. An increase in
      both left ventricular stroke volume and cardiac output due to a positive
      ventricular interaction is the mechanism leading to improved peak Vo(2).

PMID- 15145115
TI  - Urinary biopyrrins levels are elevated in relation to severity of heart failure.
AB  - OBJECTIVES: We investigated the relationship between the urinary levels of
      biopyrrins and the severity of heart failure (HF). BACKGROUND: Oxidative stress
      is evident in heart disease and contributes to the development of ventricular
      dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin,
      have been discovered as potential markers of oxidative stress. METHODS: We
      measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide
      (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects
      (30 men; mean age 65 years). Urine and blood samples were taken after admission
      in all subjects. Further urine samples were obtained from 40 patients after
      treatment of HF. RESULTS: The urinary biopyrrins/creatinine levels (micromol/g
      creatinine) were the highest in patients in New York Heart Association (NYHA)
      class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary
      biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range
      2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly
      higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant
      differences in urinary biopyrrins/creatinine levels among each group. The
      treatment of HF significantly decreased both urinary biopyrrins/creatinine levels
      (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class
      (from 2.5 +/- 0.1 to 1.7 +/- 0.1). Log biopyrrins/creatinine levels were
      positively correlated with log BNP levels (r = 0.650, p < 0.001). CONCLUSIONS:
      These results indicate that urinary biopyrrins levels are increased in patients
      with HF and are elevated in proportion to its severity.

PMID- 15145118
TI  - Long-term outcomes of cardiac pacing in adults with congenital heart disease.
AB  - OBJECTIVES: The purpose of this retrospective study was to define long-term
      outcomes after pacemaker therapy in adults with congenital heart disease (CHD).
      BACKGROUND: Adults with CHD represent a unique and expanding population. Many
      will require pacemaker or implantable defibrillator therapy, with a lifelong need
      for re-intervention and follow-up. They pose technical and management challenges
      not encountered in other groups receiving pacing, and the complication and re
      intervention rates specific to this population are not well-defined. METHODS: We
      reviewed outcomes of 168 adults with CHD, 89 females, mean age 40 years, in whom
      a pacemaker or anti-tachycardia device was implanted. RESULTS: Mean age at
      implant was 28 years with mean pacing duration 11 years at follow-up (range, 0.5
      to 38.0). Seventy-two (42%) received initial dual-chamber devices and remained in
      this mode, while 23 (14%) went from ventricular to dual-chamber pacing in follow
      up. Initial mode of pacing did not have a significant effect on subsequent atrial
      arrhythmia. Patients receiving an initial epicardial system were younger than
      those paced endocardially (17 +/- 12 years vs. 35 +/- 16 years, p < 0.001) and
      more likely to undergo re-intervention (p = 0.019). Difficulty with vascular
      access was encountered in 25 patients (15%), while 45 (27%) experienced lead
      related complications. No significant predictors of lead complications were
      identified. CONCLUSIONS: Lead complications were not significantly different for
      epicardial versus endocardial, nor physiologic versus ventricular pacing, but a
      trend toward improved lead survival in patients receiving endocardial leads at
      first implant was observed. Adults with CHD remain at risk for atrial arrhythmias
      regardless of pacing mode.

PMID- 15145119
TI  - Intrauterine pulmonary venous flow and restrictive foramen ovale in fetal
      hypoplastic left heart syndrome.
AB  - OBJECTIVES: We sought to determine whether direct foramen ovale (FO) assessment
      or pulmonary venous (PV) flow patterns in fetal hypoplastic left heart syndrome
      (HLHS) correlate with clinical markers of postnatal left atrial (LA) hypertension
      severity associated with restrictive FO. BACKGROUND: Restrictive FO places a
      newborn with HLHS at high risk of mortality and morbidity. METHODS: We reviewed
      the prenatal and postnatal echocardiograms and outcomes of 45 fetuses with
      variants of HLHS diagnosed since May 1999 to determine whether direct FO
      assessment or PV flow patterns correlate with clinical LA hypertension after
      birth. RESULTS: Direct FO assessment in utero showed a poor correlation with
      postnatal FO size, Pao(2), base excess, and the need for atrial septoplasty (p >
      0.05). In 40 fetuses with available PV spectra, three PV flow patterns were
      observed: 1). continuous forward flow with a small a-wave reversal (velocity time
      integral [VTI] for reverse/forward flow [VTIR/VTIF ratio <0.18]); 2). continuous
      forward flow with increased a-wave reversal (VTIR/VTIF ratio >or=0.18); and 3).
      brief to-and-fro flow. Among 19 live-borns, the postnatal FO diameter was smaller
      in patients with type B than in those with type A flow (1.6 +/- 1.6 mm and 4.5 +/
      2.1 mm, respectively; p = 0.0015), and all patients with type C flow had an
      intact atrial septum. All three patients with type C flow were critically ill at
      birth, requiring emergent atrial septoplasty, and two died after heart
      transplantation, whereas patients with type A or B flow were clinically stable,
      with only one postoperative death. CONCLUSIONS: Prenatal PV flow patterns in HLHS
      identify the fetus at risk of severe LA hypertension at birth.

PMID- 15145120
TI  - Cellular, but not direct, adenoviral delivery of vascular endothelial growth
      factor results in improved left ventricular function and neovascularization in
      dilated ischemic cardiomyopathy.
AB  - OBJECTIVES: We sought to compare the effects on angiogenesis and left ventricular
      (LV) function of adenoviral vascular endothelial growth factor-165 (AdVEGF-165)
      gene delivery by direct injection of AdVEGF-165 to the transplantation of
      skeletal myoblasts (SKMB) transfected with AdVEGF-165 in a rat model of ischemic
      cardiomyopathy. BACKGROUND: Angiogenesis offers the potential for treating
      ischemic cardiomyopathy. However, the optimal method of delivering angiogenic
      factors for neovascularization remains undetermined. With the increased clinical
      interest in cell therapy for the treatment of LV dysfunction, SKMB
      transplantation may serve as a means of gene transfer. METHODS: Two months after
      left anterior descending coronary artery ligation, rats received either injection
      of an adenoviral construct encoding VEGF-165, or 1 million SKMB transfected with
      AdLuciferase (AdLuc) or AdVEGF-165. Cardiac function was assessed
      echocardiographically, and neovascularization was assessed histologically four
      weeks after therapy. RESULTS: Neovascularization was significantly increased by
      both AdVEGF delivery strategies (100 +/- 7% and 185 +/- 33% increase in vascular
      density compared with SKMB alone, respectively). However, cell-based delivery,
      but not direct injection of AdVEGF-165, resulted in increased cardiac function
      (73.5 +/- 12.6% and 1.5 +/- 8.8% increase in shortening fraction compared with
      saline control; AdLuc-transfected SKMB: 29.4 +/- 15.0%). The improved function
      was not due to increased engraftment of VEGF expressing SKMB. Rather, improved
      function correlated with less apoptosis in the border zone in those animals that
      received AdVEGF-165 expressing SKMB. CONCLUSION: Our data demonstrate that cell
      based delivery of VEGF leads to an improved treatment effect over direct
      adenoviral injection, and suggest that already developed adenoviral vectors that
      encode secreted factors could potentially offer greater efficacy in combination
      with SKMB transplantation.

PMID- 15145122
TI  - Heart hospitals: for better or worse.

PMID- 15145121
TI  - Powerful and controllable angiogenesis by using gene-modified cells expressing
      human hepatocyte growth factor and thymidine kinase.
AB  - OBJECTIVES: This study investigated the possibility of achieving angiogenesis by
      using gene-modified cells as a vector. BACKGROUND: Although gene therapy for
      peripheral circulation disorders has been studied intensively, the plasmid or
      viral vectors have been associated with several disadvantages, including
      unreliable transfection and uncontrollable gene expression. METHODS: Human
      hepatocyte growth factor (hHGF) and thymidine kinase (TK) expression plasmids
      were serially transfected into NIH3T3 cells, and permanent transfectants were
      selected (NIH3T3 + hHGF + TK). Unilateral hindlimb ischemia was surgically
      induced in BALB/c nude mice, and cells were transplanted into the thigh muscles.
      All effects were assessed at four weeks. RESULTS: The messenger ribonucleic acid
      expression and protein production of hHGF were confirmed. Assay of growth
      inhibition by ganciclovir revealed that the 50% (median) inhibitory concentration
      of NIH3T3 + hHGF + TK was 1000 times lower than that of NIH3T3 + hHGF. The NIH3T3
      + hHGF + TK group had a higher laser Doppler blood perfusion index, higher
      microvessel density, wider microvessel diameter, and lower rate of hindlimb
      necrosis, as compared with the plasmid- and adenovirus-mediated hHGF transfection
      groups or the NIH3T3 group. The newly developed microvessels were accompanied by
      smooth muscle cells, as well as endothelial cells, indicating that they were on
      the arteriolar or venular level. Laser Doppler monitoring showed that the rate of
      blood perfusion could be controlled by oral administration of ganciclovir. The
      transplanted cells completely disappeared in response to ganciclovir
      administration for four weeks. CONCLUSIONS: Gene-modified cell transplantation
      therapy induced strong angiogenesis and collateral vessel formation that could be
      controlled externally with ganciclovir.

PMID- 15145123
TI  - Predictors of left ventricular dysfunction following mitral valve repair for
      mitral regurgitation.

PMID- 15145127
TI  - Characteristics of a great review.

PMID- 15145125
TI  - Composite confusion.

PMID- 15145129
TI  - [Restenosis and vascular response after angioplasty: physiopathological data].
AB  - Our purpose is to review the different mechanisms involved in the vascular
      response following percutaneous coronary revascularization, and their role in
      thrombotic complications and in restenosis. Specificities related to the various
      techniques of percutaneous coronary revascularization (balloon angioplasty,
      coronary stents, brachytherapy, drug eluting stents) are discussed.

PMID- 15145130
TI  - [Restenosis estimation at the clinical level: methodologic and angiographic
      aspects].
AB  - Quantitative coronary angiography is the most objective and reproducible method
      for estimating restenosis after coronary angioplasty. Unfortunately, it does not
      strictly reflect the clinical restenosis. Numerous angiographic criteria have
      been defined, from the binary restenosis (>50% stenosis at the site dilated)
      routinely used by the clinician, to more sophisticated quantitative criteria in
      order to quantify the intimal hyperplasia, more objective but requiring rigorous
      criteria. However, new quantitative coronary analysis softwares have not been
      developed during the last years and each team had to evaluate its intra and inter
      observer variability. However, angiographic method is still the gold standard
      method for restenosis estimation, the ideal would be to defined an angiographic
      restenosis clinically consistent and well correlated with major cardiovascular
      events.

PMID- 15145131
TI  - Genetic predictive factors in restenosis.
AB  - Restenosis is still the main drawback of percutaneous transluminal coronary
      angioplasty (PTCA). It is thought to be a multifactorial process where recoil of
      the vessel, neointimal proliferation and thrombus formation are thought to play a
      role. Until now it has proven difficult to predict restenosis on clinical and
      procedural grounds, however, genetic epidemiology might provide more insights. In
      this review several genetic variables, i.e. polymorphisms that were determined in
      relation to restenosis are described. The single nucleotide polymorphisms (SNPs)
      described in the literature so far involve; the renin-angiotensin system,
      platelet aggregation, the inflammatory response, matrix metalloproteinases,
      smooth muscle cell proliferation, lipids and oxidative stress and nitric oxide.
      Nowadays DNA-microarrays have been developed which make it possible to test 50 or
      60 polymorphisms at once. However, the risk of error due to multiple testing
      should be kept in mind. The results of the studies described should be
      interpreted with care. Many of the published studies are of relatively small
      sample size, which sometimes show more positive outcomes than the larger studies,
      this is possibly due to publication bias towards more positive results. The small
      sample size studies also exhibit wide confidence intervals. On the other hand,
      one must take into account that the process of restenosis is a multifactorial one
      and it is likely that multiple genes are involved. Thus, relatively small odds
      ratios relating to single gene contribution to restenosis can be of paramount
      importance when encompassed in the overall picture. Although still much research
      has to be done, stratification according to genetic make-up may enable tailoring
      of the interventional treatment to the individual patient.

PMID- 15145132
TI  - The influence of physical stent parameters upon restenosis.
AB  - In this paper we examine whether the structure, geometry and dimensions of
      coronary stents influence the occurrence of restenosis. Whilst many consider
      these parameters to be less important since the advent of drug-eluting stents,
      this view reveals a poor appreciation of the technological development of stents
      over the last 18 years. Early 'slotted tube' stents were completely inflexible
      and posed major problems for delivery; and early 'coil' stents had poor radial
      strength, allowing considerable tissue prolapse. Nowadays, we are used to greatly
      improved physical stent parameters, which provide better deliverability,
      visibility, procedural success and scaffolding performance. Many of these
      physical parameters also impact upon restenosis, even in the current era of drug
      eluting stent. In this paper we examine the contribution of mode of expansion
      (self vs. balloon-expandable), design (coil vs. tube), length and width to
      restenosis. We also consider the more subtle influence of advanced slotted tube
      vs. modular design, percent metal coverage, strut thickness, strut shape, surface
      smoothness and alloy composition.

PMID- 15145133
TI  - [Predictive factors of restenosis: what changes with "active" stents?].
AB  - For many years, restenosis was the major limiting factor of coronary angioplasty,
      even since the systematic use of stents. Numerous scientific publications have
      aimed to define the predictive factors of this phenomenon. Factors such as
      diabetes, the size of the treated artery, the use of stents or not, the length of
      the lesion, lesion located on the proximal left anterior descending artery, the
      degree of residual stenosis post-angioplasty (assessed by angiography or by
      intravascular ultrasound) have all been evoked as being classically related to
      restenosis. However, our perception of the restenosis phenomenon has been
      dramatically changed by the demonstration of the efficacy and security of active
      stents. Even in so-called "at risk" populations, the use of active stents is
      rarely followed by restenosis. In this way, the classic risk factors for
      restenosis have now become arguments in favour of the implantation of an active
      stent. As long as budgetary constraints limit the use of active stents to
      patients said to be "at risk of restenosis", this population, quite
      paradoxically, will have a more favourable outcome than so-called "low risk"
      patients, in whom "ordinary" non-active stents will continue to be used.

PMID- 15145135
TI  - [Treatment of intrastent restenosis].
AB  - In-stent restenosis (ISR) remains an important limitation after stent
      implantation occurring in 20-30% of patients. Different techniques and treatments
      have been evaluated in this setting. Repeat balloon angioplasty alone has been
      rapidly followed by ablative techniques such as laser, rotational atherectomy or
      implantation of a second stent within the stent. Cutting balloon represents
      another alternative technique. None of these techniques has proven its
      superiority over plain balloon angioplasty alone. Brachytherapy is the only
      effective treatment for ISR by significantly decreasing recurrent restenosis rate
      at follow-up. However, its use is limited by cost and infrastructure associated
      with the risk of late thrombosis requiring prolonged antiplatelet therapy.
      Surgical treatment can be proposed in recurrent ISR as well as medical therapy
      alone in pauci-symptomatic patients. New drug-eluting stents are under evaluation
      in this indication.

PMID- 15145134
TI  - [Gene therapy of restenosis and atherosclerosis: hopes and facts].
AB  - Stents are the main technique of coronary revascularization in France and western
      countries. However, a better understanding of the pathophysiology of in-stent
      restenosis and the well-recognized roles played by inflammation and cell
      proliferation led to the development of drug-eluting stents, which have nearly
      eliminated the risk of restenosis. In this context, the success of gene therapy
      will depend on our ability to simplify and optimize current protocols of arterial
      gene transfer. For the time being, arterial gene therapy remains a powerful tool
      for deciphering the complex pathophysiology of restenosis and will certainly have
      far-reaching implications in the fields of vascular biology and therapeutics.

PMID- 15145136
TI  - [In 2003, what are the indications of brachytherapy in coronary arteries?].
AB  - Significant results obtained with coated stents in "de novo" coronary lesion
      treatment, particularly in complex lesions, have substituted brachytherapy
      indications. However, curitherapy results in diffuse or proliferative in-stent
      restenosis treatment show a significant reduction (30-50%) of restenosis and
      major adverse cardiac events. So, without sufficient scientific proofs with
      active stents in this indication, curitherapy is the only validated and
      authorized treatment of second diffuse or proliferative in-stent restenosis.

PMID- 15145137
TI  - [Active stents: towards total prevention of restenosis?].
AB  - To avoid in-stent restenosis, a new technologic approach with "coated" stents may
      deliver local cytostatic products (sirolimus, paclitaxel, tacrolimus...). At this
      time, present clinical studies validate the importance of these active coated
      stents in sub-groups of patients with diabetes, long lesions, small vessels and
      proximal left anterior descending coronary lesions.

PMID- 15145138
TI  - Quantitative models of Pavlovian conditioning.
AB  - Over the last few years, research on learning and memory has become increasingly
      interdisciplinary. In the past, theories of learning, as a prerogative of
      psychologists, were generally formulated in purely verbal terms and evaluated
      exclusively at the behavioral level. At present, scientists are trying to build
      theories with a quantitative and biological flavor, seeking to embrace more
      complex behavioral phenomena. Pavlovian conditioning, one of the simplest and
      ubiquitous forms of learning, is especially suited for this multiple level
      analysis (i.e., quantitative, neurobiological, and behavioral), in part because
      of recent discoveries showing a correspondence between behavioral phenomena and
      associative properties at the cellular and systems levels, and in part because of
      its well established quantitative theoretical tradition. The present review,
      examines the mayor quantitative theories of Pavlovian conditioning and the
      phenomena to which they have been designed to account. In order to provide
      researchers from different disciplines with a simple guideline about the
      rationale of the different theoretical choices, all the models are described
      through a single formalism based on the neural network connectionist perspective.

PMID- 15145139
TI  - Autonomic and emotional responses to open and hidden stimulations of the human
      subthalamic region.
AB  - We performed a microstimulation study of the subthalamic region of Parkinsonian
      patients who underwent bilateral electrode implantation in the subthalamic nuclei
      and whose heart rate and heart rate variability were recorded. The stimulation of
      the dorsalmost region, which includes the zona incerta and the dorsal pole of the
      subthalamic nucleus, produced autonomic responses that were constant over time.
      In fact, hidden stimulations (the patient is not aware of being stimulated) and
      open stimulations (the patient is aware of being stimulated) always induced the
      same responses. By contrast, the stimulation of the ventralmost region, which
      includes the ventral pole of the subthalamic nucleus and the substantia nigra
      pars reticulata, produced autonomic and emotional responses that were inconstant
      over time and varied according to the condition. In fact, different responses
      were elicited with hidden and open stimulations. These data suggest that the
      dorsal subthalamic nucleus and/or the zona incerta are involved in autonomic
      control, whereas the ventral subthalamic nucleus and/or the substantia nigra
      reticulata are involved in associative/limbic-related autonomic activity. The
      difference between the open and hidden stimulations in the ventral subthalamic
      region can explain previous studies in which open and hidden stimulations
      produced different therapeutic outcomes.

PMID- 15145141
TI  - Place learning and object recognition by rats subjected to transection of the
      fimbria-fornix and/or ablation of the prefrontal cortex.
AB  - The acquisition of a water maze-based allocentric place learning task and an
      exploration based object recognition task were studied in four groups of rats:
      animals in which the fimbria-fornix had been transected, rats who had received
      bilateral ablations of the anteromedial prefrontal cortex, animals in which both
      of these structures had been lesioned, and a sham operated control group. None of
      the groups showed impairments of object recognition. Ablations of the prefrontal
      cortex caused a mild impairment in the acquisition of the place learning task.
      The two fimbria-fornix transected groups exhibited a severe impairment during the
      acquisition of this task. All groups reached criterion level task performance
      eventually. All groups were subjected to a number of behavioural and
      pharmacological challenges in order to elucidate the neural and cognitive
      mechanisms of this behavioural recovery. During a no-platform session both the
      fimbria-fornix transected group and the prefrontally ablated group demonstrated a
      normal preference for the former platform position. The combined lesion group,
      however, failed to show a similar preference for this position. The outcome of
      the pharmacological challenges demonstrated that while the task performance of
      all four groups relied equally on catecholaminergic mediation, only the task
      solution of the fimbria-fornix transected group was significantly impaired by
      disturbance of the catecholaminergic systems. The data indicated a high
      likelihood that prefrontal cortical mechanisms contribute to the recovery of
      allocentric place learning after fimbria-fornix transections.

PMID- 15145140
TI  - Does hypnotizability modulate the stress-related endothelial dysfunction?
AB  - Previous studies suggest that hypnotizability represents a protective factor
      against the cardiac effects of cognitive stress and that hypnosis prevents
      vascular stress-induced modifications in highly hypnotizable individuals. The aim
      of the experiment was to investigate whether a similar effect at vascular level
      is present in awake subjects with a high (Highs) and a low (Lows) hypnotic
      susceptibility. Thus, brachial artery post-ischaemic flow-mediated vascular
      dilation (FMD) was evaluated non-invasively by ultrasound methodology during
      cognitive stress (mental computation) in Highs and Lows. Results showed that
      Highs, similarly to that previously observed in hypnotized Highs and in contrast
      with Lows, did not exhibit any stress-related endothelial dysfunction (FMD
      decrement). Thus, hypnotizability should be considered a protective factor
      against vascular disease.

PMID- 15145142
TI  - Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor
      activation.
AB  - Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)
      agonistic-like effects in behavioral pharmacology test. However, there is to date
      no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The
      object of the present study was to assess the effects of mirtazapine on dialysate
      levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats
      and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In
      vivo microdialysis was used to study the effects of mirtazapine on extracellular
      dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on
      extracellular dopamine level increased by mirtazapine in the rat prefrontal
      cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in
      extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely
      moving rats without modifying those of 5-HT. In the presence of the selective 5
      HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N
      (pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence
      of mirtazapine on cortical levels of dopamine was markedly attenuated. These
      results indicate that mirtazapine induces the enhancement of the output of
      cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and
      facilitation of post-synaptic 5-HT(1A) function.

PMID- 15145143
TI  - Involvement of serotonin 5HT1 and 5HT2 receptors and nitric oxide synthase in the
      medial preoptic area on gonadotropin secretion.
AB  - Due to the stimulatory action of serotonin (5HT) and nitric oxide (NO) on the
      secretion of gonadotropins and PRL, this work aimed at investigating the
      participation of serotoninergic receptors 5HT(1) and 5HT(2) of the medial
      preoptic area (MPOA) in the control of luteinizing hormone (LH), follicle
      stimulating hormone (FSH) and prolactin (PRL) secretion and the possible
      modulation by ovarian steroids as well as the possible participation of NO as a
      mediator of the stimulatory effects of serotonin in the MPOA on LH secretion.
      Microinjections of three different doses (0.02, 0.2, and 2 ug) of methiothepin, a
      serotoninergic 5HT(1) antagonist or ketanserin, a seretoninergic 5HT(2)
      antagonist, were carried out into the MPOA in ovariectomized rats treated or not
      with estrogen or estrogen plus progesterone. Other groups of ovariectomized rats
      treated with estrogen, estrogen plus progesterone or vehicle were prepared to
      evaluate NOS activity in the MPOA. Plasma LH, FSH, and PRL in ovariectomized rats
      were not altered by the microinjection of methiothepin or ketanserin in the MPOA.
      Methiothepin microinjection in the MPOA reduced LH but did not change plasma FSH
      and PRL in ovariectomized rats treated with estrogen or estrogen plus
      progesterone. On the other hand, ketanserin microinjection in the MPOA reduced
      plasma LH and FSH but did not change plasma PRL in the animals submitted to the
      same steroidal treatment. NOS activity in the MPOA was significantly reduced by
      methiothepin or ketanserin in ovariectomized rats treated with estrogen or
      estrogen plus progesterone. In conclusion, this work showed that in the studied
      conditions, serotonin in the MPOA: (1) does not work in the control of PRL
      secretion through 5HT(1) and 5HT(2) receptors; (2) integrates the control of FSH
      secretion by 5HT(2) receptors, but not 5HT(1); (3) in the presence of estrogen,
      stimulates LH secretion by 5HT(1) and 5HT(2) receptors, which can be
      differentially modulated by progesterone; (4) at least partly, stimulates LH
      secretion by nitric oxide activity.

PMID- 15145144
TI  - Release of amino acids by zinc in the hippocampus.
AB  - Zinc exists in the synaptic vesicles of hippocampal mossy fibers in high
      concentrations. On the basis of inhibitory zinc action against glutamate release
      in the hippocampus, the role of zinc in release of several amino acids were
      studied in rat hippocampus by using in vivo microdialysis. When the hippocampal
      CA3 region was perfused with 10 microM ZnCl(2), the concentrations of glutamine,
      serine, arginine, aspartate, and glycine in the perfusate were significantly
      increased, whereas the concentrations of amino acids except for glycine were not
      increased by perfusion with 30 microM ZnCl(2). Chelation of endogenous zinc with
      50 microM CaEDTA significantly decreased the concentrations of amino acids in the
      perfusate except for glycine. In the CA1 region, on the other hand, the
      concentrations of these five amino acids were not increased by perfusion with 10
      microM ZnCl(2) and the concentrations of glutamine and glycine were decreased
      significantly. The present study suggests that zinc enhances release of
      glutamine, serine, arginine, and aspartate in the CA3 region and attenuates
      release of glutamine and glycine in the CA1 region. Zinc seems to modulate
      glutamatergic synapses multifunctionally in the hippocampus, because glutamine,
      serine, aspartate, and glycine are involved in synaptic neurotransmission.

PMID- 15145145
TI  - Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy
      radiotherapy.
AB  - PURPOSE: We compared the long-term results of postprostatectomy radiotherapy (RT)
      from two institutions, one adapting a prospective policy of adjuvant RT and the
      other salvage RT. METHODS AND MATERIALS: Between 1989 and 1997, 69 patients were
      referred for adjuvant RT to the institution using adjuvant RT and 88 patients
      with evidence of recurrence were treated in the institution using salvage RT. The
      salvage group underwent RT after longer postoperative intervals (median, 40.3 vs.
      2.9 months; p <0.0001) and had higher prostate-specific antigen (PSA) values
      before starting RT (4.5 vs. 0.86 ng/mL; p = 0.003). Both groups were routinely
      treated to a minimal total dose of 60 Gy. The treatment groups were analyzed for
      overall survival, disease-specific survival, distant metastasis-free survival,
      and biochemical recurrence-free survival (BRFS) using Cox proportional hazards
      modeling. RESULTS: Of the 69 patients referred for adjuvant RT, 22 (32%) had
      nonzero PSA values before RT. Multivariable modeling of BRFS found only the PSA
      value before RT to be statistically significant (p <0.0001). RT after
      prostatectomy was equally effective in either setting when the pre-RT PSA level
      was <1 ng/mL. When the PSA value before RT was >or=1 ng/mL, the 5-year BRFS for
      each group was inferior. CONCLUSION: Although the adjuvant treatment policy was
      associated with significantly improved BRFS, this was attributable to low pre-RT
      PSA values. When the treatment groups were stratified for pre-RT PSA level, the
      differences in BRFS were not statistically significant. Patients with a rising
      PSA level after prostatectomy, regardless of their initial risk, should receive
      prompt referral for RT.

PMID- 15145146
TI  - Radiotherapy after radical prostatectomy: does transient androgen suppression
      improve outcomes?
AB  - PURPOSE: The long-term biochemical relapse-free survival and overall survival
      were compared for patients receiving either radiotherapy (RT) alone or
      radiotherapy combined with a short-course of total androgen suppression for
      failure after radical prostatectomy. METHODS AND MATERIALS: Between 1985 and
      2001, a total of 122 patients received RT after radical prostatectomy at our
      institution. Fifty-three of these patients received a short-course of total
      androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a
      nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH)
      agonist (combined therapy group); the remaining 69 patients received RT alone.
      Treatment failure was defined after postoperative RT as a detectable PSA >0.05
      ng/mL. Clinical and treatment variables examined included: presurgical PSA,
      clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement,
      lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic
      irradiation, indication for postoperative RT (salvage or adjuvant), and time
      interval between surgery and RT. Minimum follow-up after postoperative RT was 1
      year and median follow-up was 5.9 years (maximum, 14 years) for patients
      receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT
      with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA
      failure-free survival (bNED) and for overall survival (OS). Cox proportional
      hazards multivariable analysis examined the influence all clinical and treatment
      variables predicting for bNED and OS. RESULTS: The median time to PSA failure
      after postoperative RT was 1.34 years for the combined therapy group and 0.97
      years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5
      years, the actuarial bNED rates were 57% for the combined therapy group compared
      with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years
      were 100% for the combined therapy group compared with 87% for the RT alone group
      (p = 0.0008). For pGS <or=7, the 5-year bNED rates were 58% for combined therapy
      and 38% for RT alone (p = 0.0155), and for pGS >or=8 the 5-year bNED rates were
      65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates
      for pGS <or=7 were 100% for combined therapy and 98% for RT alone group (p =
      0.106), and the 5-year OS for pGS >or=8 was 100% for combined therapy and 54% for
      RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145)
      and the addition of short-course TAS to postoperative RT (p = 0.0019) were
      significant covariates predicting for bNED and, similarly, approached
      significance for overall survival (p = 0.0594 and p = 0.0856, respectively).
      CONCLUSIONS: Radiotherapy combined with a short-course TAS after radical
      prostatectomy appears to confer a PSA relapse-free survival advantage and
      possibly an overall survival advantage when compared with RT alone. The
      hypothesis that a transient course of androgen suppression with salvage or
      adjuvant RT after prostatectomy improves outcomes will need to be tested in a
      randomized trial.

PMID- 15145147
TI  - Proton therapy for prostate cancer: the initial Loma Linda University experience.
AB  - PURPOSE: We analyzed results of conformal proton radiation therapy for localized
      prostate cancer, with emphasis on biochemical freedom from relapse. METHODS AND
      MATERIALS: Analyses were performed for 1255 patients treated between October 1991
      and December 1997. Outcomes were measured on primarily in terms of biochemical
      relapse and toxicity. RESULTS: The overall biochemical disease-free survival rate
      was 73%, and was 90% in patients with initial PSA <or=4.0; it was 87% in patients
      with posttreatment PSA nadirs <or=0.50. Rates dropped with rises in initial and
      nadir PSA values. Long-term survival outcomes were comparable with those reported
      for other modalities intended for cure. CONCLUSIONS: Conformal proton radiation
      therapy at the reported dose levels yielded disease-free survival rates
      comparable with other forms of local therapy, and with minimal morbidity. Dose
      escalation strategies are being implemented to further improve long-term results.

PMID- 15145148
TI  - Dose-volume response analyses of late rectal bleeding after radiotherapy for
      prostate cancer.
AB  - PURPOSE: To compare the fits of various normal tissue complication probability
      (NTCP) models to a common set of late rectal toxicity data, with the aim of
      identifying the best model for predicting late rectal injury after irradiation.
      METHODS AND MATERIALS: Late toxicity data from 128 prostate cancer patients
      treated on protocol with three-dimensional conformal radiotherapy at The
      University of Texas M.D. Anderson Cancer Center (UTMDACC) were analyzed. The dose
      volume histogram for total rectal volume, including contents, was obtained for
      each patient, and the presence or absence of Grade 2 or worse rectal bleeding
      within 2 years of treatment was scored. Five different NTCP models were fitted to
      the data using maximum likelihood analysis: the Lyman model, the mean dose model,
      a parallel architecture model, and models based on either a cutoff dose or a
      cutoff volume. RESULTS: All five of the NTCP models considered provided very
      similar fits to the UTMDACC rectal bleeding data. In particular, none of the more
      highly parameterized models (the four-parameter parallel model, three-parameter
      Lyman model, or three-parameter cutoff dose and volume models) provided a better
      fit than the simplest of the models, the two-parameter NTCP model describing
      rectal bleeding as a probit function of mean dose to rectum. CONCLUSION: No dose
      volume response model has yet been identified that provides a better description
      of the UTMDACC rectal toxicity data than the mean dose model. Because this model
      has relatively low predictive accuracy, the need to identify a better model
      remains.

PMID- 15145149
TI  - Target repositioning optimization in prostate cancer: is intensity-modulated
      radiotherapy under stereotactic conditions feasible?
AB  - PURPOSE: To assess repositioning reproducibility of the prostate when treatment
      setup conditions before radiotherapy (RT) are optimized and internal organ motion
      is reduced with an endorectal inflatable balloon. METHODS AND MATERIALS: Thirty
      two patients were treated with 64 Gy to the prostate and seminal vesicles using a
      three-dimensional conformal radiotherapy technique, followed by a boost (two
      fractions of 5-8 Gy, 3-5 days apart) delivered to a reduced prostate volume (the
      peripheral tumor bearing zone with 3-mm margins) using intensity-modulated RT. A
      commercially available infrared-guided stereotactic repositioning system and a
      rectal balloon were used. Further improvement in repositioning could be obtained
      with a stereoscopic X-ray registration device matching the pelvic bones during
      treatment with the corresponding bones in the planning computed tomography (CT).
      To simulate repositioning reproducibility, CT resimulation was performed before
      the last boost fraction. Prostate repositioning was reassessed, first after CT-to
      CT fusion with the stereotactic metallic body markers of the infrared-guided
      system, and second after CT-to-CT registration of the pelvic bony structures.
      RESULTS: Standard deviations of the prostate (CTV) center of mass shifts in the
      three axes ranged from 2.2 to 3.6 mm with body marker registration and from 0.9
      to 2.5 mm with pelvic bone registration. The latter improvement was significant,
      particularly in the right-to-left axis (3.5-fold improvement). In 10 patients,
      systematic rectal probe repositioning errors (i.e., >20-mL probe volume
      variations or >8-mm probe shifts in the perpendicular axes) were detected. Target
      repositioning was reassessed excluding these 10 patients. An additional
      improvement was observed in the anteroposterior axis with 1.7 times and 1.5 times
      reduction of the standard deviation with body markers and pelvic bone
      registrations, respectively. CONCLUSIONS: Infrared-guided target repositioning
      for prostate cancer can be optimized with a stereoscopic X-ray positioning device
      mostly in the right-to-left axis. An optimally positioned inflatable rectal probe
      further optimizes target repositioning mostly along the anteroposterior axis.
      Thus a planning target volume with a margin of 2 (right-to-left), 4
      (anteroposteriorly), and 6 (craniocaudally) mm around the CTV can be recommended
      under optimal setup conditions with pelvic bone registration and optimal
      repositioning of an inflated rectal balloon.

PMID- 15145150
TI  - External beam radiotherapy for clinically node-negative, localized hormone
      refractory prostate cancer: impact of pretreatment PSA value on radiotherapeutic
      outcomes.
AB  - PURPOSE: To analyze the results of clinically node-negative, localized hormone
      refractory prostate cancer treated with external beam radiotherapy (EBRT) and to
      investigate the potential prognostic factors that influenced the therapeutic
      outcome. METHODS AND MATERIALS: Fifty-three patients who had developed localized
      hormone-refractory prostate cancer were treated with EBRT between 1994 and 2001.
      According to the 1992 American Joint Committee on Cancer clinical stage, 4
      patients had T2 and 49 had T3 at the start of RT, and 14 patients had a Gleason
      score <7, 14 had a Gleason score of 7, and 23 had a Gleason score of 8-10. All
      patients were treated with EBRT using the unblocked oblique four-field technique,
      with a total dose of 69 Gy. The fraction dose was 3 Gy three times weekly. The
      median follow-up after RT was 35 months (range, 8-96 months) and after androgen
      ablation was 73 months (range, 42-156 months). RESULTS: Of 53 patients, 15
      patients subsequently developed clinical relapse, including locoregional and/or
      distant metastases. The site of first relapse was bone metastasis in 10, lymph
      nodes in 3, and local failure in 2 patients; 3 patients died of prostate cancer
      during the analysis period. The 3-year and 5-year cause-specific survival rate
      was 94% and 87%, respectively, and the 3-year and 5-year clinical relapse-free
      survival rate was 78% and 56%, respectively. The univariate analysis revealed
      that a short prostate-specific antigen (PSA) doubling time and high PSA value at
      the start of RT and a high Gleason score were statistically significant factors
      for the risk of clinical relapse. Multivariate analysis demonstrated that the PSA
      value (PSA <or=15 vs. >or=15 ng/mL) at the start of RT was an independent
      prognostic factor. CONCLUSION: EBRT could be a treatment of choice for clinically
      node-negative, localized, hormone-refractory prostate cancer.

PMID- 15145151
TI  - A comparison of the single and double factor high-risk models for risk assignment
      of prostate cancer treated with 3D conformal radiotherapy.
AB  - PURPOSE: Two models for stratification of prostate cancer aggressiveness
      predominate for the purposes of daily treatment decision making. This study
      investigates the relationships between these two clinically popular models.
      METHODS: Both risk stratification models use the same definition for low risk:
      Gleason score (GS) <or=6, pretreatment initial prostate specific antigen (iPSA)
      <or=10 ng/mL, and stage T1c-T2c. For the single factor high risk model (SF),
      intermediate risk (IR) is defined as the presence of GS 7 or PSA > 10-20 ng/mL,
      without the presence of any high-risk feature; high risk (HR) was defined as the
      presence of GS 8-10, iPSA >20, or palpation stage T3. For the double factor high
      risk (DF) model, IR and HR were defined as one and more than one of the
      following: GS >or=7, iPSA >10, or stage T3. Between April 1989 and October 2001,
      1,597 patients were treated definitively with 3D conformal radiation therapy (3D
      CRT) alone for prostate cancer at our institution. The main clinical endpoint was
      freedom from biochemical failure (FFBF). RESULTS: The 5-year actuarial FFBF rate
      for the low-risk group was 83%. The SF model resulted in FFBF rates of 76% and
      47% for IR and HR patients respectively. The DF model resulted in FFBF rates of
      70% and 52% for IR and HR patients, respectively. The FFBF rate for patients
      defined as IR and HR by both models was 76% and 40%, respectively. Those
      classified as IR by the DF model and then further subdivided into IR and HR by
      the SF model had a 76% and 52% 5-year FFBF rate (p = 0.0004). Those classified as
      HR by the DF model and then further subdivided into IR and HR by the SF model had
      a 71% and 40% 5-year FFBF (p = 0.0014). CONCLUSIONS: The SF model created
      prognostic groups with a greater internal consistency than the DF model. The SF
      was also better at identifying patients with high-risk prostate cancer who may
      benefit from a more aggressive approach.

PMID- 15145153
TI  - Prostate brachytherapy can be performed in selected patients after transurethral
      resection of the prostate.
AB  - PURPOSE: To evaluate urinary function and bother after prostate brachytherapy
      (PB) in patients who have had prior transurethral resection of the prostate
      (TURP). METHODS AND MATERIALS: A total of 171 patients with stage T1a-T2b
      prostate cancer, Gleason score <or=7 who underwent prior TURP received PB at a
      single institution. In January 2002, all 171 patients were mailed the University
      of California-Los Angeles Prostate Cancer Index and International Prostate
      Symptom Score sheet. One hundred patients (60%) returned completed surveys. Time
      of TURP before implant ranged from 2 to 300 months (median, 6.5 years). Mean
      patient age was 74 +/- 5.2 years, follow-up time after implant ranged from 6.1 to
      50.9 months (median, 25 months). RESULTS: The mean urinary function score and
      bother score for the entire study group was 83.5 +/- 19.5 and 82.5 +/- 23.7,
      respectively. Multivariate analysis revealed higher pretreatment International
      Prostate Symptom Scores to have significant negative impact (p = 0.001) on
      urinary function and bother scores. CONCLUSION: With accurate ultrasound
      identification of the urethral defect and precise dosimetry, brachytherapy can be
      performed in selected patients who have had prior TURP with resultant low impact
      on urinary function and bother scores.

PMID- 15145152
TI  - Extended prostate biopsy scheme improves reliability of Gleason grading:
      implications for radiotherapy patients.
AB  - BACKGROUND: With sextant prostate biopsies, there is up to a 1-in-3 chance that
      the underlying pathologic Gleason grade is higher. Knowledge of the underlying
      grade might have significantly altered the therapeutic recommendations and
      management for patients electing radiotherapy for localized prostate cancer
      (e.g., eligibility for brachytherapy, androgen suppression with external beam
      radiotherapy, elective pelvic radiotherapy). This study examines the concordance
      patterns between biopsy and matched radical prostatectomy Gleason grade among
      patients undergoing an extended 10-core biopsy scheme to assess its reliability
      compared to sextant biopsies. METHODS AND MATERIALS: Seventy-eight consecutive
      patients underwent an extended 10-core peripheral zone biopsy scheme (sextant
      plus two lateral mid and two lateral base biopsies) and subsequent radical
      prostatectomy at this institution between mid-2000 and mid-2003. No patient
      received androgen suppression. All histologic grading were made by a single
      pathologist (J.E.M.). Needle biopsies were characterized for location, linear
      involvement of cancer within positive cores, and total number of positive cores.
      Radical prostatectomy specimens were step-sectioned at 3-mm intervals and were
      characterized for total cancer volume and percentage of each Gleason grade
      present. Clinical parameters available included digital rectal exam, preoperative
      PSA, and ultrasound prostate volume. A "clinically significant" upgrading of the
      biopsy was defined as any of the following: (1) a biopsy Gleason score (bGS) of 6
      to a pathologic GS (pGS) of 7 or higher, (2) a bGS 3 + 4 to a pGS of 4 + 3 or
      higher, and (3) a bGS of 7 to a pGS of 8 or higher. Statistical analyses were
      performed on the patterns Gleason score concordance between biopsies and matched
      radical prostatectomies. RESULTS: An exact Gleason score match between biopsy and
      prostatectomy was observed in 62% of patients using the sextant biopsy scheme
      (SB), an upgrading of 1 or more grade points was seen in 25% and a downgrading of
      1 or more points in 13% for SB. These rates of grade discordance are comparable
      to those of published sextant series. An exact match using the extended biopsy
      scheme (EB) was 63% (p = 0.61 compared with SB), whereas upgrading was 13% (p =
      0.045 compared with SB) and downgrading was 24% (p = 0.06 compared with SB). A
      "clinically significant" upgrading as defined here was present in 38.1% of the SB
      group compared with 23.1% of the EB group (p = 0.039). For patients with bGS of
      6, a clinically significant upgrading occurred in 66.7% with SB and in 36.8% with
      EB (p = 0.068). Upgrading of the primary Gleason grade from 3 to 4/5 was seen in
      41.8% for the SB and in 25.5% for the EB group (p = 0.078). No clinical factors
      (T-stage, PSA, prostate volume, % positive cores, linear extent of cancer) were
      found to predict for a clinically significant upgrading of biopsies on logistic
      regression analysis. CONCLUSIONS: The extended 10-core biopsy scheme
      significantly improves on sextant biopsies in predicting the underlying
      pathologic Gleason score for prostate cancer. In particular, it is superior to
      sextant biopsies in revealing the presence of an underlying high-grade component.
      The potential clinical impact this improvement has for patients ultimately
      selecting radiotherapy suggests that an extended biopsy scheme should become the
      standard of care. Nevertheless, even with this improvement, there still remains
      up to a 1-in-5 chance that the underlying grade will be higher.

PMID- 15145154
TI  - The use of linked seeds eliminates lung embolization following permanent seed
      implantation for prostate cancer.
AB  - PURPOSE: A number of reports of (125)I seed migration to the lungs after prostate
      brachytherapy have been published. There are, however, very limited data
      available on how to reduce the risk of this event. The purpose of the present
      report is to determine whether seed embolization to the lungs can be minimized by
      using stranded seeds alone for brachytherapy. METHODS AND MATERIALS: Between
      December 2001 and December 2002, 238 patients with early prostate cancer were
      treated with prostate brachytherapy as monotherapy using (125)I stranded seeds
      (RAPIDStrand) exclusively. All patients had fluoroscopy during the implant and
      immediate postimplant radiographs of the pelvis. A sample of 100 patients had
      chest radiographs performed, on average, 55 days after implant. To determine the
      ease, or lack of ease, with which these (125)I seeds could be visualized, 4
      patients who did not have prostate cancer and who were having routine chest
      radiographs as part of their management for other cancers consented to have
      posteroanterior and lateral radiographs performed with inactive (125)I seeds
      taped to the skin of the thorax. All radiographs were reviewed by a single
      radiologist. RESULTS: The number of seeds noted on the postimplant radiographs
      corresponded to the number of implanted seeds in all 238 cases: There was,
      therefore, no evidence of seed embolization immediately postimplant. On review of
      the 100 chest radiographs, no embolized seeds were found. CONCLUSION: No evidence
      of seed embolization was observed with the use of stranded (125)I seeds as used
      for prostate brachytherapy.

PMID- 15145155
TI  - Quantifying the impact of seminal vesicle invasion identified using endorectal
      magnetic resonance imaging on PSA outcome after radiation therapy for patients
      with clinically localized prostate cancer.
AB  - PURPOSE: This study examined the impact that seminal vesicle invasion (SVI),
      observed on endorectal magnetic resonance imaging (erMRI), had on prostate
      specific antigen (PSA) outcome after external beam radiation therapy (EBRT) for
      patients with clinically localized prostate cancer. METHODS AND MATERIALS: The
      study cohort was comprised of 250 patients who received 3D conformal radiation
      therapy without hormones for clinically localized prostate cancer between 1992
      and 2001. The primary end point was PSA failure, defined using the American
      Society for Therapeutic Radiology and Oncology consensus definition. Cox
      regression multivariable analysis was used to determine the ability of the
      pretreatment risk group and erMRI SVI to predict for time to PSA failure after
      EBRT. RESULTS: Both risk group (p(Cox) = 0.001) and erMRI SVI (p(Cox) = 0.003)
      were independent and significant predictors of time to PSA failure. For patients
      beyond low risk, 4-year estimates of PSA failure-free survival for erMRI SVI
      negative vs. erMRI SVI-positive patients were 68% vs. 33% (p(log-rank) = 0.0014),
      respectively. CONCLUSION: Patients with clinically localized disease and PSA >10
      or biopsy Gleason score >or=7 or clinical T category T2b or T2c who also have
      erMRI evidence of SVI have PSA outcomes similar to patients with locally advanced
      prostate cancer after EBRT monotherapy. Consideration should be given to
      combining EBRT with hormonal therapy in these patients.

PMID- 15145156
TI  - Long-term follow-up of radiotherapy for prostate cancer.
AB  - PURPOSE: To determine the long-term outcome of radiotherapy for prostate cancer.
      METHODS AND MATERIALS: A total of 136 consecutive patients with prostate cancer
      underwent primary radiotherapy. All but 4 patients received 6000 cGy to the
      prostate. The minimal follow-up was 22.9 years. RESULTS: Of the 136 patients, 93
      had Stage B (T2), 9 Stage A (T1), and 34 Stage C (T3). Sixty-nine percent of the
      patients developed recurrence, and 51% of all patients died of prostate cancer.
      The recurrences developed at a steady state throughout the length of follow-up.
      One half the recurrences occurred after 10 years, and recurrence was still
      observed >20 years after treatment. The survival rate at 5, 10, 15, 20, and 25
      years was 81%, 59%, 37%, 16%, and 10%, respectively. The recurrence-free survival
      rate at 25 years was 17%. The median survival for Grade 3-4 patients was 6.3
      years and for Grade 1-2 patients was 13.0 years. The median survival for those
      with T1 tumors was 12.9 years; T2 tumors, 12.4 years; and T3 tumors, 9.5 years.
      CONCLUSION: Despite favorable early results, with long-term follow-up, patients
      continued to experience prostate cancer recurrence. Unless they died an
      intercurrent death, they were highly likely to develop recurrence and die of
      prostate cancer. The conclusions from treatment studies with <15 years of follow
      up should be viewed as preliminary.

PMID- 15145157
TI  - Evaluation of a contour-alignment technique for CT-guided prostate radiotherapy:
      an intra- and interobserver study.
AB  - PURPOSE: The recent introduction of integrated CT/linear accelerator systems may
      mean that daily CT localization can become a reality in the clinic, possibly
      allowing further dose escalation to the prostate while limiting unwanted doses to
      the rectum and bladder. However, the implementation of CT localization is
      currently impeded by the lack of precise and robust techniques to align the
      treatment plan with the daily CT images. The purpose of this study was to
      evaluate a manual alignment technique, in which the gross target volume contours
      are overlaid on the daily CT images and then shifted to match the structures
      visible in the images. METHODS AND MATERIALS: A total of 28 CT image sets were
      taken before the standard delivery of intensity-modulated radiotherapy for
      prostate cancer for 2 patients. Seven observers (four radiation oncologists and
      three medical physicists) manually shifted the gross target volume contours from
      the treatment plan to best match the daily CT images. One observer repeated the
      process 1 week later to evaluate intraobserver variations. The experiment was
      then repeated, but the CT images from the original treatment plan were used as a
      reference to reduce interobserver uncertainty when aligning the contours. The
      shifts in prostate position found by different observers, both with and without
      reference data, were evaluated using a factorial analysis of variance to
      determine the standard errors of measurement for the intra- and interobserver
      uncertainty (SEM(intra) and SEM(inter), respectively). The differences in the SEM
      for the two groups of observers (radiation oncologists and medical physicists),
      the two alignment techniques (with and without reference information), and the
      two patients were evaluated using the t test at 90% confidence levels. RESULTS:
      With no reference information, the SEM(inter) using one patient data set (Patient
      1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right-left (RL), anterior-posterior
      (AP), and superior-inferior (SI) directions, respectively. The use of the
      treatment plan as a reference reduced the SEM(inter) to 0.7 mm, 1.0 mm, and 1.6
      mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of
      the prostate was more difficult; the best SEM(inter) achieved with this patient
      was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively.
      The SEM(intra) values with Patient 1 were also slightly better than with Patient
      2. When reference data were used, the SEM(intra) value was 0.5 mm, 0.7 mm, and
      0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP,
      and SI directions, respectively. Despite the larger than expected interobserver
      variation reported here, the SEM(inter) was smaller than the typical day-to-day
      variation in prostate position. The contour alignment technique may still be
      useful to aid daily prostate localization or in a correction scheme to minimize
      the effect of target positional error. CONCLUSION: The interobserver
      uncertainties associated with aligning the gross target volume contours with
      daily CT images were sufficiently small that this method may be used for daily CT
      localization of the prostate. The use of a reference image is important to
      improve the consistency among different users in this technique.

PMID- 15145158
TI  - Radioactive seed migration to the chest after transperineal interstitial prostate
      brachytherapy: extraprostatic seed placement correlates with migration.
AB  - PURPOSE: To examine the incidence of seed migration detected on chest X-ray and
      to identify the predictors associated with its occurrence. METHODS AND MATERIALS:
      Between May 1998 and April 2000, 102 patients underwent permanent prostate
      brachytherapy at our institution and 100 were eligible for the study. Chest X
      rays obtained at follow-up were examined for the number and location of seeds.
      The patient and treatment variables potentially associated with the occurrence
      and number of seed migrations were analyzed. RESULTS: One or more seeds were
      identified on the chest X-rays of 55 (55%) of 100 patients. The mean number of
      intrathoracic seeds in patients with migration was 2.2 (range, 1-10), and the
      proportion of seeds that migrated to the thorax was 0.98%. The rate of
      extraprostatic seeds planned was 43.9%, and postimplant CT identified 37.9% in
      such a location. The number of seeds planned for extraprostatic placement and
      below the apex were statistically significant (alpha = 0.05) predictors in
      univariate logistic analysis. Multivariate analysis revealed the planned number
      of extraprostatic seeds as the only statistically significant predictor (p =
      0.04). CONCLUSION: Extraprostatic placement of loose seeds is associated with an
      increased likelihood for, and frequency of, seed migration to the thorax.
      Nonetheless, the small proportion of implanted seeds that migrated (<or=1%) is
      highly unlikely to have significant dosimetric consequences.

PMID- 15145159
TI  - Localization of neurovascular bundles on pelvic CT and evaluation of radiation
      dose to structures putatively involved in erectile dysfunction after prostate
      brachytherapy.
AB  - PURPOSE: To (a) locate neurovascular bundles (NVB) on pelvic CT and (b)
      retrospectively evaluate relationships between radiation dose to structures
      putatively involved in prostate brachytherapy-induced erectile dysfunction (ED)
      and incidence of postbrachytherapy ED. METHODS AND MATERIALS: (a) Right/left NVB
      were identified on nine prostate MRIs. Structures visible on MRI and CT were
      cross-referenced. Cross-sectional area of each NVB was measured. (b) All patients
      treated with implant alone and whose treatment was planned on Variseed (Varian
      Medical Systems, Palo Alto, CA), with follow-up of >12 months were included; n =
      41. Median follow-up was 20 months. All patients were potent (+/- sildenafil)
      before implant (erection sufficient for intercourse). The right/left NVB (using
      results from part "a"), penile bulb, and right/left crus were outlined on
      postimplant CT. Volumes and doses to these structures were calculated. RESULTS:
      (a) On prostate MRI, NVB was consistently located where the prostate border bends
      away from the levator ani, at the gland's smallest radius of curvature. Average
      area of the circle best encompassing the NVB = 0.27 cm(2); diameter was 0.58 cm.
      (b) 11 of 41 (27%) patients had ED; 30 of 41 were potent (15 with sildenafil).
      There was no significant difference between potent/impotent patients in isotope,
      age, diabetes, hypertension, follow-up, or volume of prostate, bulb, right/left
      NVB, or right/left crus. There was a relationship between smoking and ED (p =
      0.05). There was a relationship between bulb %D90 and ED: >10% 67% (4 of 6) vs.
      <10% 20% (7 of 35) (p = 0.03), which remained when controlling for smoking. There
      was no relationship between dose to left NVB and potency. There was paradoxical
      decreased risk of ED with right NVB %V100 >60% (p = 0.019), and right NVB %D60
      >100% (p = 0.003). There was no relationship between dose to right/left crus and
      ED. CONCLUSIONS: A reliable method for localizing NVB on CT is demonstrated.
      There is no increased risk of prostate brachytherapy-induced ED with increasing
      dose to crus or NVB at the doses given in this study. There is a possible dose
      response relationship between dose to the bulb and risk of ED.

PMID- 15145160
TI  - Impact of changes in bladder and rectal filling volume on organ motion and dose
      distribution of the bladder in radiotherapy for urinary bladder cancer.
AB  - PURPOSE: To determine the impact of filling volume changes of the urinary bladder
      and rectum on organ motion and dose distribution of the bladder and rectum during
      radical radiotherapy for bladder cancer and to calculate the internal margins to
      secure target coverage. METHODS AND MATERIALS: In 15 patients with muscle
      invasive bladder cancer, a planning CT scan was performed with a bladder and
      rectal catheter, followed by three immediate CT scans with various filling of the
      urinary bladder and rectum. After 20 fractions, a fifth CT scan, without
      catherization, was performed. In each CT study, the bladder and rectum volumes
      were delineated and matched to the planning CT scan to measure the organ motion
      and calculate internal margins. These margins were compared with an isotropic
      standard margin of 2 cm. Dose-volume histograms were analyzed to describe the
      dose distribution in the bladder and rectum corresponding to various filling
      volumes. RESULTS: Bladder movement was most pronounced in the anterior and
      cranial directions. The internal margins required to cover the bladder movements
      due to filling of the bladder and rectum in 87% of the patients were 2.4 cm in
      the anterior, 1.1 cm in the posterior, 3.5 cm in the cranial, 0.5 cm in the
      caudal, and 1.3 cm in the lateral direction. CONCLUSION: The filling volumes of
      the bladder and rectum have a large impact on bladder movements, especially in
      the anterior and cranial directions. This should be included in the internal
      target volume with the introduction of anisotropic margins in conformal
      radiotherapy for bladder cancer.

PMID- 15145161
TI  - Intensity-modulated radiotherapy in treatment of pancreatic and bile duct
      malignancies: toxicity and clinical outcome.
AB  - PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy
      (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND
      MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated
      with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a
      pancreatic primitive neuroectodermal tumor received concurrent etoposide and
      ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary
      (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning
      with conventional three-dimensional four-field techniques for dosimetric
      comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the
      mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well
      tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a
      median follow-up of 10.2 months, no resected patients had local failure, and only
      1 of 10 assessable patients with unresectable cancer had local progression. The
      median survival and distant metastasis-free survival of the 24 patients with
      adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity
      occurred in 1 patient surviving >5 years. The remainder of the assessable
      patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In
      this hypothesis-generating analysis, the acute and chronic toxicity profile with
      IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local
      control was not compromised, despite efforts to increase conformality and avoid
      doses to normal structures. Distant failure remains a major obstacle in
      pancreatic cancer.

PMID- 15145162
TI  - Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for
      pancreatic cancer.
AB  - PURPOSE: Local failure continues to be a major problem in the management of
      pancreatic cancer. Delivery of adequate radiation doses to the pancreas is
      limited by radiation-sensitive normal structures in the upper abdomen. To
      overcome some of these restrictions, we have developed a regimen of intensity
      modulated radiotherapy (IMRT) with concurrent capecitabine. METHODS AND MATERIAL:
      This is a retrospective analysis of the first 15 patients with adenocarcinoma of
      the pancreas treated on this regimen (7 as adjuvant therapy after curative
      resection and 8 patients for unresectable disease). Intensity-modulated
      radiotherapy was planned using the CORVUS system and delivered with a segmented
      multileaf collimator, using a 6-MV photon beam and 10 intensity steps. Two target
      volumes were entered: target 1 consisted of the gross tumor volume (in
      unresectable cases) or the tumor bed (in postsurgical cases); and target 2
      consisted of the draining lymph nodes. Both targets were treated simultaneously
      in 25 daily fractions, 5 days a week. In the postoperative setting, the total
      dose to target 1 was 45-54 Gy (median, 54 Gy). For unresectable disease the dose
      was 54-55 Gy (median, 54 Gy). The total dose to target 2 was 45 Gy in all
      patients. Patients were treated with one of two six-field beam arrangements found
      to produce superior dose distributions. Capecitabine was given at 1,600
      mg/m(2)/day in two divided doses, 5 days per week, concurrently with
      radiotherapy. In addition, most patients (73%) received gemcitabine-based
      chemotherapy. Systemic chemotherapy was given before, after, or both before and
      after chemoradiotherapy in 47%, 7%, and 20% of patients, respectively. Patients
      were evaluated on a weekly basis. RESULTS: Treatment was tolerated well. Grade
      1/2 nausea/vomiting developed in 8 patients (53%) and Grade 1/2 hematologic
      toxicity developed in 9 patients (60%). Only 1 patient (7%) had Grade 3 toxicity,
      a gastric ulceration that responded to medical management. Nine patients (60%)
      had weight loss (median, 7 lbs; range, 3-12 lbs). The median follow-up time is
      8.5 months (10.1 months in patients who are alive). In the resectable group there
      have been no deaths, and there has been 1 local relapse (14%). In the
      unresectable group there have been 2 deaths, and the 1-year actuarial survival
      rate is 69%. Two patients converted to resectability, 5 patients (62.5%) have
      persistent locoregional disease after chemoradiotherapy, and 1 patient (12%) is
      locally controlled without surgery. CONCLUSIONS: This regimen of IMRT with tumor
      selective radiosensitization is well tolerated. The low toxicity profile compares
      favorably with that of protocols based on continuous-infusion 5-fluorouracil or
      gemcitabine, and the preliminary indications of efficacy are encouraging.

PMID- 15145163
TI  - 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited
      stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study
      39808.
AB  - PURPOSE: To prospectively evaluate the feasibility of delivering 70 Gy once-daily
      thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of
      limited-stage small-cell lung cancer (L-SCLC). MATERIALS AND METHODS: Eligible
      patients received two cycles of induction paclitaxel (175 mg/m(2) on Day 1) and
      topotecan (1 mg/m(2) on Days 1-5) with granulocyte colony stimulating factor
      support, followed by three cycles of carboplatin (area under the curve = 5 on Day
      1) and etoposide (100 mg/m(2) on Days 1-3). TRT (70 Gy, 2 Gy/fx/7 weeks) was
      initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial
      irradiation was offered to patients achieving a complete response or good partial
      response. RESULTS: Ninety percent of patients (57 of 63) proceeded to protocol
      TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4
      toxicities affecting more than 10% of patients, during or after TRT, were
      dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all
      therapy was 92% and the median overall survival is 22.4 months (95% confidence
      interval 16.1, infinity ). Twenty-eight patients remain alive with a median
      follow-up of 24.7 months. CONCLUSION: 70 Gy once-daily TRT can be delivered
      safely in the cooperative group setting for patients with L-SCLC. Initial
      efficacy data are encouraging. The hypothesis that high-dose once-daily TRT
      results in comparable or improved survival compared with twice-daily accelerated
      TRT warrants testing in a Phase III trial.

PMID- 15145164
TI  - Treatment volume and dose optimization of MammoSite breast brachytherapy
      applicator.
AB  - PURPOSE: Limited information has been reported on the dosimetry achieved with the
      MammoSite breast brachytherapy applicator. We present our results regarding the
      volume of treatment and a comparison of a single prescription point, single dwell
      position optimization technique with a six prescription point, multiple dwell
      position method. METHODS AND MATERIALS: Between October 14, 2002 and February 28,
      2003, 21 patients with early-stage breast cancer were treated using the MammoSite
      device. The treatment was delivered in 10 fractions of 3.4 Gy/fraction, b.i.d.,
      with a minimum of 6 hours between the daily fractions. CT of the lumpectomy
      cavity was obtained both with and without the inflated balloon. A planning target
      volume was constructed using a three-dimensional planning system. A three
      dimensional expansion of the balloon surface was performed using the chest wall
      and skin as limiting structures. The volume of the inflated balloon was removed
      from this volume, and the volume of tissue treated in each patient was
      determined. A sequential expansion in 1-mm increments around the empty lumpectomy
      cavity was performed until the closest equivalent volume to the planning target
      volume was obtained. The treatment for the patients in this study was planned
      using both a single prescription point, single dwell position optimization
      technique and a six-prescription point, multiple dwell position technique. The
      single prescription point method has been described in a previous publication.
      The six-prescription point method used six points placed 1 cm from the balloon
      surface. Four points are in a plane transverse to the balloon axis perpendicular
      to the axis of the catheter, and two points are placed along the axis of the
      catheter. The prescription points along the catheter axis are used to compensate
      for the decreased dose coverage owing to anisotropy dose distribution of the
      source. The Nucletron HDR Plato Brachytherapy planning system was used to
      optimize the source positions and dwell times. RESULTS: The volume of breast
      tissue treated by the MammoSite device was equal to the volume encompassed by a
      mean 1.6-cm (SD, 0.1) margin around the empty lumpectomy cavity. Compared with
      the single prescription point optimization method, the six prescription point
      method provided better dose coverage, with a mean percentage of volume receiving
      90% of the prescription dose of 97.2% (SD = 2.1) vs. 89.5% (SD = 4.6) for the
      single-point method. The mean percentage of volume receiving 100% of the
      prescription dose was 88.9% (SD = 3.3) for the six-point method vs. 77.6% (SD =
      6.1) for the single-point method. However, compared with the single-point method,
      the six-point optimization method resulted in treatment that was less uniform,
      with a mean dose homogeneity index of 0.62 (SD =.07) vs. 0.66 (SD =.08) for the
      single-point method. CONCLUSION: The volume of normal breast tissue treated by
      the MammoSite device is comparable to other methods of interstitial brachytherapy
      that treat a 1-2-cm margin of tissue around the excision cavity. The six
      prescription point, multiple dwell position method improved dose coverage with a
      slight decrease in dose homogeneity. The six-point method offers greater
      reliability of dose coverage compared with the single-point method by providing
      an increased number of reference points.

PMID- 15145165
TI  - Soft tissue sarcomas treated with postoperative external beam radiotherapy with
      and without low-dose-rate brachytherapy.
AB  - PURPOSE: Patients treated for soft tissue sarcoma with adjuvant low-dose-rate
      brachytherapy (BT) plus external beam radiotherapy (EBRT) were compared with
      those treated with adjuvant EBRT alone. The hypothesis was that higher doses from
      postoperative BT plus EBRT would improve local tumor control. METHODS AND
      MATERIALS: The medical records of 130 sarcoma patients definitively treated
      between February 1983 and February 2001 were reviewed. Of these, 25 patients
      received BT followed by EBRT, and 61 were treated with EBRT alone. Overall
      survival, freedom from distant metastasis, and local control were calculated
      using Kaplan-Meier estimates. Univariate and multivariate analyses were
      performed. The mean postoperative radiation dose with EBRT alone was 59 Gy
      (range, 50-74) and 50 Gy (range, 40-70 Gy) when low-dose-rate BT was included.
      The mean implant dose was 16 Gy (range, 10-20 Gy). RESULTS: The 5-year Kaplan
      Meier estimate for overall survival for BT plus EBRT and EBRT alone was 82% and
      72% (p = 0.93), respectively. The 5-year freedom from distant metastasis and
      freedom from local failure rate for BT plus EBRT vs. EBRT alone was 90% vs. 78%
      (p = 0.15) and 90% vs. 83% (p = 0.25), respectively. In the univariate subset
      analysis, Stage III patients had better local control at 5 years (100% vs. 62%, p
      = 0.03) and a trend was noted for better local control for high-grade tumors
      (100% vs. 74%, p = 0.09) if treated with BT plus EBRT. No statistically
      significant predictors were found on multivariate analysis for local control. The
      median follow-up was 62 months. CONCLUSION: Local control at 5 years was high in
      both groups at 83% and 90%. On univariate analysis, Stage III patients had
      improved 5-year local control and a trend was found toward better local control
      for high-grade tumors. On multivariate analysis, no predictors were found for
      better local control; however, the numbers of Stage III and high-grade patients
      were small, which may have masked a possible benefit of BT plus EBRT in this
      population.

PMID- 15145166
TI  - Neoadjuvant docetaxel, cisplatin, 5-fluorouracil before concurrent
      chemoradiotherapy in locally advanced squamous cell carcinoma of the head and
      neck versus concomitant chemoradiotherapy: a phase II feasibility study.
AB  - PURPOSE: To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5
      fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared
      with the same CHT-RT regimen alone in locally advanced head-and-neck squamous
      cell carcinoma. METHODS AND MATERIALS: We treated 24 patients (20 men and 4
      women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity,
      oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years
      (range, 41-73 years). The stage distribution was as follows: Stage II, 1 patient;
      Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of
      0 and 6 had a performance status of 1. None had undergone previous CHT or RT.
      Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on
      Days 1-4 and 5-fluorouracil 600 mg/m(2)/d continuous infusion for 96 h) starting
      on Days 1, 22, and 43 during RT (one daily fraction, 66-70 Gy within 33-35
      fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75
      mg/m(2), cisplatin 80 mg/m(2), 5-fluorouracil 800 mg/m(2)/d continuous infusion
      for 96 h) followed by the same CHT-RT regimen. RESULTS: After the first 16
      patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was
      modified. The limiting toxicity observed during concomitant CHT-RT was similar in
      Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4
      mucositis and other relevant toxicity that did not allowing completion of CHT-RT
      without interruption occurred in 44% of the patients. A reduction of at least one
      cycle of concurrent CHT was required in 31% of patients. On the basis of these
      data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF
      followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5
      fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and
      6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World
      Health Organization G3-G4 mucositis. No World Health Organization hematologic G3
      G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1
      patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and
      3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis
      (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1)
      and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3). CONCLUSION:
      Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are
      feasible without limiting toxicity. Three cycles of TPF were well tolerated and
      did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase
      III study has been started with the aim of comparing two cycles of PF during RT
      as standard treatment vs. the experimental arm with three cycles of neoadjuvant
      TPF followed by two cycles of PF during RT.

PMID- 15145167
TI  - Cost analysis comparing brachytherapy versus surgery for primary carcinoma of the
      tonsillar fossa and/or soft palate.
AB  - PURPOSE: Locoregional control rates, late normal tissue sequelae, and functional
      outcome scores have not been different for tonsillar fossa and/or soft palate
      tumors treated by either brachytherapy (BT) or surgery in an organ function
      preservation protocol. For additional prioritizing in clinical decision-making,
      we focused on a comparison of the full hospital costs of the different treatment
      options. METHODS AND MATERIALS: Between 1986 and 2001, tonsillar fossa and/or
      soft palate tumors were treated by external beam radiotherapy (EBRT) to the
      primary tumor and neck, followed by fractionated BT to the primary. Neck
      dissection (ND) was performed for node-positive disease (BT group; 104 patients).
      If BT was not feasible, resection combined with postoperative EBRT was executed
      (surgery group; 86 patients). Locoregional control, disease-free survival, and
      overall survival were calculated according to the Kaplan-Meier method. The
      performance status scales, late side effects, and degree of xerostomia have been
      previously reported. This paper focused on the hospital and follow-up costs for
      the treatment groups EBRT and BT with or without ND compared with surgery
      followed by postoperative RT (PORT). Finally, these costs were also computed for
      future treatment strategies (e.g., better sparing of normal tissues by intensity
      modulated RT [IMRT]). RESULTS: Locoregional control, disease-free survival, and
      overall survival rate at 5 years for patients treated with EBRT and BT with or
      without ND vs. surgery plus PORT was 80% vs. 78%, 58% vs. 55%, and 67% vs. 57%,
      respectively. The major late side effect was xerostomia. Dry mouth syndrome
      affected the BT group and surgery group equally. The total costs for all
      treatment groups were 14,262 euro (BT group), 16,628 euro (BT plus ND group),
      18,782 euro (surgery plus PORT group), 14,532 euro (IMRT group), and 16,897 euro
      (IMRT plus ND group). CONCLUSION: Excellent locoregional tumor control was
      observed with either modality, with no statistically significant differences in
      the incidence of the most noted side effect xerostomia. The total costs for BT
      were less than for surgery: 16,628 euro (19,452 dollars) for EBRT plus BT plus ND
      vs. 18,782 euro(22,074 dollars) for surgery plus PORT. To reduce the morbidity of
      xerostomia, we propose further optimizing our organ function preservation
      protocol by implementing IMRT as a more conformal, tissue-sparing, RT technique.
      This is of particular interest because the costs of IMRT plus ND (16,897 euro;
      19,767 dollars) were not very different from those for BT plus ND (16,628 euro;
      19,452 dollars) and were far less than the costs for surgery.

PMID- 15145168
TI  - A multi-institutional retrospective analysis of external radiotherapy for mucosal
      melanoma of the head and neck in Northern Japan.
AB  - PURPOSE: A multi-institutional retrospective study was performed in northern
      Japan to analyze the outcome of external radiotherapy as the definitive treatment
      modality for localized mucosal melanoma of the head and neck. PATIENTS AND
      METHODS: Thirty-one patients with localized mucosal melanoma of the head and neck
      treated by external radiotherapy at nine institutions of the Northern Japan
      Radiation Therapy Oncology Group between 1980 and 1999 were enrolled in this
      study. Radiotherapy alone was performed in 21 patients, and the remaining 10
      patients received postoperative radiotherapy for gross residual tumors. The
      fraction size of radiotherapy varied from 1.5-13.8 Gy, with the total dose
      ranging from 32-64 Gy (median, 50 Gy). The follow-up periods ranged from 1-214
      months (median, 16 months). RESULTS: Complete or partial responses were observed
      in 9 patients (29%) and 18 patients (58%), respectively. Local recurrence
      occurred in 13 patients (41.9%) and distant metastasis occurred in 11 patients
      (35.5%). Most incidences of local recurrence and distant metastasis developed
      within 2 years after the initial treatment. Overall cause-specific survival rates
      of patients at 1 and 3 years were 73% and 33%, respectively. Univariate analysis
      showed that high dose per fractionated radiotherapy doses (>or=3 Gy) was
      associated with better prognosis for both local control (p = 0.048) and survival
      (p = 0.045). Multivariate analysis indicated that age (better prognosis in
      younger patients, p = 0.046) was the only significant factor. Radiotherapy for
      gross residual lesions after surgery did not seem to impact the significant gain
      of local control and survival. We observed two fatal late complications of
      mucosal ulcer and bleeding in the high dose per fractionated radiotherapy group.
      CONCLUSION: Radiotherapy at a dose of 3 Gy or more per fraction was effective in
      gaining local control in patients with localized mucosal melanoma of the head and
      neck, and subsequently better survival was possible, especially in younger
      patients.

PMID- 15145169
TI  - Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM
      chemotherapy before radiotherapy: long-term survival and prognostic factors.
AB  - PURPOSE: To assess the long-term survival and prognostic factors associated with
      the cyclophosphamide, doxorubicin, vincristine, and dexamethasone
      (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) and BVAM
      chemotherapy regimens followed by cranial radiotherapy in the treatment of
      primary central nervous system (CNS) non-Hodgkin lymphoma. METHODS AND MATERIALS:
      Since 1986, high-dose methotrexate (1.5 g/m(2)), cytarabine, vincristine, and
      carmustine have been used in the BVAM chemotherapy regimen for primary CNS non
      Hodgkin's lymphoma, with one cycle of CHOD given before BVAM in patients <or=70
      years of age from 1990 onward. RESULTS: The median age for the 77 patients
      treated was 60 years and the median follow-up of surviving patients was 3 years
      (range, 1.4-15.2 years). The complete response rate after chemotherapy was 62%
      and after additional radiotherapy was 73%. Multivariate analysis of overall
      survival showed age (p = 0.004), performance status (p = 0.007), and number of
      tumors (unifocal disease vs. multifocal disease; p = 0.005) to be statistically
      significant prognostic factors. Survival decreased with increasing age and
      performance status score. Using a prediction score giving 1 point for each
      adverse prognostic factor (age >or=60 years, performance status >or=2, and
      multifocal and/or meningeal disease [advanced stage]), a score of 0 (8 patients)
      was associated with a median survival of 55 months, a score of 1 (29 patients) of
      41 months, a score of 2 (28 patients) of 32 months, and a score of 3 (12
      patients) a median survival of 1 month (p <0.001). The actuarial overall survival
      for the 35 patients aged <60 years was 32.4% (95% confidence interval, 14.1
      50.8%) at 10 years. CONCLUSION: The Nottingham/Barcelona prediction score, which
      is similar to the International Prognostic Index, may be useful in comparing
      survival with different regimens studied in Phase II trials. Patients with
      primary CNS non-Hodgkin's lymphoma aged <60 years treated with CHOD/BVAM or BVAM
      followed by radiotherapy have a similar long-term survival to that of patients
      with large B cell non-Hodgkin's lymphoma at other extranodal sites.

PMID- 15145171
TI  - Coverage of anterior fossa in whole-brain irradiation.
AB  - PURPOSE: Whole-brain irradiation is indispensable in the treatment of several
      brain tumors and requires coverage of the entire subarachnoid space.
      Retrospective studies have revealed frequent recurrences in the frontobasal fossa
      above the cribriform plate (CP). We sought to determine how accurately the latter
      could actually be identified on lateral radiographs such as those used for
      radiotherapy planning. METHODS AND MATERIALS: The CP was localized by five
      radiation oncologists and five radiologists on lateral radiographs of 30 human
      skulls from an anatomic collection. Reference radiographs were acquired under
      identical conditions except for lead markers pointing to the CP and the ethmoid
      cells. The targeting accuracy was analyzed. RESULTS: In 39% (n = 116), the
      location of the CP was correctly estimated within 2 mm. Mislocations of 2-5, 5
      10, and >10 mm were noted in 34% (n = 102), 20% (n = 61), and 7% (n = 21),
      respectively. Neither specialty nor experience (years of training) exerted a
      significant influence on targeting accuracy. If the roofs of the ethmoid cells
      formed prominent bony edges, they were mistaken for the CP in 37%. CONCLUSION:
      Lateral radiographs provide insufficient information to locate the CP accurately
      in whole brain irradiation. Additionally, localization was significantly impaired
      by prominent ethmoid cells.

PMID- 15145170
TI  - Combined treatment modality for anaplastic oligodendroglioma and
      oligoastrocytoma: a 10-year update of a phase II study.
AB  - PURPOSE: To provide updated outcome data (10 years) of a Phase II study of
      combined surgery, postoperative radiotherapy, and adjuvant chemotherapy in
      patients with anaplastic oligodendroglioma and oligoastrocytoma. METHODS AND
      MATERIALS: In 23 adult patients, surgery, postoperative radiotherapy (60 Gy in 30
      daily fractions within 6 weeks), and adjuvant modified chemotherapy (procarbazine
      60 mg/m(2) on Days 1-14, lomustine 100 mg/m(2) on Day 1, and vincristine 1.4
      mg/m(2) [maximum 2 mg] on Days 1 and 8) were administered every 6 weeks for up to
      six cycles or until progression occurred. RESULTS: The median follow-up was 116
      months for all patients. The median survival time was 118 months, and the 5-year
      and 10-year survival rate was 57% and 47%, respectively. The median time to tumor
      progression was 78 months, with a 5-year and 10-year progression-free survival
      rate of 52% and 39%, respectively. Gender, age, Karnofsky performance status,
      location, and histologic type did not influence survival. Patients with tumors
      <or=4 cm did better than those with tumors >4 cm (p = 0.0470), as did those with
      total tumor resection compared with those with subtotal tumor resection or biopsy
      only (p = 0.0024). Gender, Karnofsky performance status, location, and histologic
      type did not influence progression-free survival, but younger age (p = 0.0389),
      smaller tumor size (p = 0.0357), and more radical surgery (p = 0.0033) correlated
      positively with it. Acute high-grade (Grade 3 or worse) chemotherapy-related
      toxicity was mainly hematologic, with 3 patients (13%) experiencing acute Grade 4
      toxicity. CONCLUSION: The results of this 10-year update confirmed that the
      trimodality approach is effective in patients with anaplastic oligodendroglioma
      and oligoastrocytoma.

PMID- 15145172
TI  - Long-term treatment results of invasive cervical cancer patients undergoing
      inadvertent hysterectomy followed by salvage radiotherapy.
AB  - PURPOSE: To evaluate the long-term results of salvage radiotherapy for patients
      of invasive cervical cancer after inadequate surgery. METHODS AND MATERIALS:
      Between October 1975 and January 1994, 90 patients were treated with radiotherapy
      for invasive cervical carcinoma after simple hysterectomy. The inadequate surgery
      was performed for a variety of reasons. All patients had postoperative external
      beam irradiation or intravaginal brachytherapy, or both. The end points of this
      study were local control, survival, and treatment-related toxicity. RESULTS: The
      patients' age varied between 33 and 76 with a median of 53 years. The most common
      histopathology was squamous cell carcinoma, which accounted for 91% of the
      patients. The most frequent reason for inadvertent hysterectomy was understaged
      disease with preoperative diagnosis as carcinoma in situ for 51 patients (57%).
      Malignancy was not suspected before surgery in 28 patients (31%). After surgery,
      72 patients (80%) were restaged as Ib, 12 patients (13.3%) as IIa, and 6 patients
      (6.7%) as IIb. Median follow-up time was 83 months. Seventy-three patients had
      follow-up times of 5 years or more. The overall 5-year and 10-year survival rates
      of 90 patients were 85.5% and 74.1%, respectively. Disease-specific 5-year and 10
      year survival rates were 85.5% and 80.5%, respectively. All 16 patients with
      either locoregional or distant failure eventually died of disease. Fourteen
      patients (15.5%) had late morbidities. Radiation proctitis developed in 6
      patients, intestinal obstruction in 4 patients, and hemorrhagic cystitis in 3.
      There was only 1 patient (1%) with terminal ileum stenosis and severe intestinal
      obstruction requiring surgical intervention. CONCLUSIONS: Most cases of
      inadequately treated invasive cervical cancer were the result of suboptimal
      preoperative workups. Patients who had early tumors and no gross residual tumor
      after inadequate hysterectomy can have excellent prognoses when given
      postoperative radiotherapy. The severe long-term complication related to salvage
      radiotherapy is rare.

PMID- 15145173
TI  - Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone
      Metastasis Study controlling for the influence of retreatment.
AB  - PURPOSE: The Dutch Bone Metastasis Study on the effect on painful bone metastases
      of 8 Gy single fraction (SF) vs. 24 Gy in multiple fractions (MF) showed 24%
      retreatment after SF vs. 6% after MF (p < 0.001). The purpose of the present
      study was to evaluate factors influencing retreatment and its effect on response.
      METHODS AND MATERIALS: The database on all randomized patients was reanalyzed
      with separately calculated responses to initial treatment and retreatment.
      RESULTS: Response to initial treatment was 71% after SF vs. 73% after MF (p =
      0.84). Retreatment raised response to 75% for SF; MF remained unaltered (p =
      0.54). The response status after initial treatment did not predict occurrence of
      retreatment: 35% SF vs. 8% MF nonresponders and 22% SF vs. 10% MF patients with
      progressive pain were retreated. Logistic regression analyses showed the
      randomization arm and the pain score before retreatment to significantly predict
      retreatment (p < 0.001). Retreatment for nonresponders was successful in 66% SF
      vs. 33% MF patients (p = 0.13). Retreatment for progression was successful in 70%
      SF vs. 57% MF patients (p = 0.24). CONCLUSIONS: With or without the effect of
      retreatment, SF and MF radiotherapy provided equal palliation for painful bone
      metastases. Irrespective of response to initial treatment, physicians were more
      willing to retreat after a single fraction. Overall, retreatment was effective in
      63% of retreated patients.

PMID- 15145174
TI  - Clinical effects in a cohort of cancer patients overexposed during external beam
      pelvic radiotherapy.
AB  - PURPOSE: To evaluate the clinical outcome of 28 overexposed cancer patients in a
      cohort of 153 treated with pelvic irradiation and to correlate the outcome with
      the doses received. METHODS AND MATERIALS: Between August 2000 and March 2001,
      153 patients were treated at the Instituto Oncologico Nacional of Panama with
      radiotherapy for cancers of the cervix, uterus, endometrium, prostate, and rectum
      using conventional techniques. In 56 patients, irradiated with partially blocked
      teletherapy fields, the treatment times were determined using a treatment
      planning system that generated isodose distributions. The absorbed doses received
      by the patients were calculated and the biologically effective doses (BEDs) and 2
      Gy equivalent doses derived. The clinical outcome was evaluated using the
      Radiation Therapy Oncology Group (RTOG) and late effects on normal tissues
      subjective, objective, management, analytic scales (LENT/SOMA). The relationships
      between clinical outcome and dose were investigated and compared with published
      data. RESULTS: Of the 56 patients for whom treatment times were generated with
      the treatment planning system, 28 received some doses per fraction approximately
      double those prescribed. Using an alpha/beta = 10 Gy, the tumor BED(10) values
      ranged from 77 to 225 Gy. The rest of the patients received doses within 10% of
      the prescribed values. Seventeen of the 28 overexposed patients died 35 days to
      21 months after treatment; 13 of the fatalities were caused by rectal
      complications. Survival was longer in those patients who had undergone colostomy.
      Bladder complications were less enhanced. The nonoverexposed patients with
      cervical cancer exhibited a greater incidence of treatment failures than
      generally reported in other centers. CONCLUSION: This study provides the clinical
      outcome after high doses of pelvic radiotherapy in a range not previously well
      documented. For cervical cancer patients receiving both tele- and brachytherapy,
      some deaths in this overexposure cohort occurred from assumed consequential
      rectal injury within 2 years, when the BED(10) values exceeded 70-80 Gy. The
      incidence was asymptotic to 100% fatalities at >150 Gy. This confirmed and
      extended other data in the literature.

PMID- 15145175
TI  - Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon
      irradiation as evaluated by equivalent uniform dose and dose volume histogram
      analysis.
AB  - PURPOSE: To evaluate cervical spinal cord tolerance using equivalent uniform dose
      (EUD) and dose volume histogram (DVH) analysis after proton-photon radiotherapy.
      METHODS AND MATERIAL: The 3D dose distributions were analyzed in 85 patients with
      cervical vertebral tumors. Mean follow-up was 41.3 months. The mean prescribed
      dose was 76.3 Cobalt Gray Equivalent (CGE = proton dose x RBE 1.1). Dose
      constraints to the center and the surface of the cervical cord were 55-58 CGE and
      67-70 CGE, respectively. Dose parameters, DVH and EUD, were calculated for each
      patient. The spinal cord toxicity was graded using the European Organization for
      Research and Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group
      (RTOG) late effects scoring system. RESULTS: Thirteen patients experienced Grade
      1-2 toxicity. Four patients had Grade 3 toxicity. For the dose range used in this
      study, none of the dosimetric parameters was found to be associated with the
      observed distribution of cord toxicities. The only factor significantly
      associated with cord toxicity was the number of surgeries before irradiation.
      CONCLUSION: The data and our analysis suggest that the integrity of the normal
      musculoskeletal supportive tissues and vascular supply may be important
      confounding factors of toxicity at these dose levels. The results also indicate
      that the cervical spinal cord dose constraints used in treating these patients
      are appropriate for conformal proton-photon radiotherapy.

PMID- 15145176
TI  - Differential attenuation of clavicle growth after asymmetric mantle radiotherapy.
AB  - PURPOSE: To determine the effects of 15 Gy on bone growth as a function of time
      and age by comparing clavicle length before and after asymmetric mantle
      irradiation in pediatric patients. METHODS AND MATERIALS: We measured the lengths
      of both clavicles from radiographs made before and after radiotherapy (median
      follow-up, 39.6 months), in 15 children (median age, 13.3 years) with early-stage
      Hodgkin's disease treated with combined modality therapy. The intercepts and
      slopes of regression lines for individual patients were used to form an
      estimating regression curve for the population. RESULTS: The irradiated volume,
      patient age, and time elapsed after treatment influenced the measured growth.
      Fully irradiated clavicles grew 1.3 +/- 0.3 cm, significantly less (0.5 cm; p =
      0.007) than did the partially irradiated clavicles. The difference between
      partially and fully irradiated clavicle lengths was statistically significant,
      regardless of age. Also, the growth rate of partially and fully irradiated
      clavicles was significantly different between younger (mean age, 9.9 years) and
      older (mean age, 16.4 years) patients (p = 0.036). CONCLUSION: Clavicle growth is
      vulnerable to radiation doses as low as 15 Gy, and patient age at the time of
      irradiation influences the growth rate.

PMID- 15145178
TI  - Synergistic effects of hyperoxic gas breathing and reduced oxygen consumption on
      tumor oxygenation: a theoretical model.
AB  - PURPOSE: To simulate effects of reduced oxygen consumption combined with
      hyperoxic gas breathing on tumor oxygenation, and to test for synergistic
      effects. METHODS AND MATERIALS: Diffusive oxygen transport was simulated for a
      small region of tumor containing a three-dimensional network of microvessels
      whose geometry was derived from in vivo observations. Changes in tissue partial
      pressure of oxygen (PO(2)) and hypoxic fraction (PO(2) < 5 mm Hg) resulting from
      a 30% reduction in oxygen consumption rate or breathing 100% oxygen were
      estimated. The synergistic effect was defined as the change in PO(2) with the two
      treatments combined, minus the sum of the changes with the separate treatments.
      RESULTS: Predicted hypoxic fractions were 37% in the control state, 11% with
      reduced consumption, 23% with oxygen breathing alone, and 0% with the combined
      treatment. The synergistic effect was about 4 mm Hg at tissue points with very
      low initial PO(2) levels and decreased as initial PO(2) increased. CONCLUSIONS:
      Reduction of oxygen consumption via the Crabtree effect, by administration of
      glucose, has been proposed as a means to improve tumor oxygenation during
      radiation treatment. The results support previous experimental studies showing
      that this approach is more effective when combined with breathing of hyperoxic
      gases.

PMID- 15145177
TI  - Enhanced systemic T-cell activation after in situ gene therapy with radiotherapy
      in prostate cancer patients.
AB  - PURPOSE: In situ cytotoxic gene therapy can potentially trigger a systemic immune
      response, which could impact occult metastatic disease. We are currently
      conducting three clinical trials using in situ adenoviral vector mediated herpes
      simplex virus-thymidine kinase (HSV-tk) gene delivery followed by the HSV-tk
      prodrug ganciclovir (GCV) or valacyclovir (VCV). This study evaluates the
      systemic T-cell response after gene therapy in each trial. METHODS AND MATERIALS:
      The study protocol included three separate clinical trials in the Baylor Prostate
      Cancer SPORE Program: Trial A gene therapy in prostate cancer patients failing
      radiotherapy (36 patients), Trial B neoadjuvant gene therapy in pre-radical
      prostatectomy patients (22 patients), and Trial C gene therapy in combination
      with radiotherapy for prostate cancer (27 patients). Heparinized blood was
      collected at the time of vector injection and at selected intervals afterward. A
      complete blood count was performed, and peripheral blood lymphocytes were
      analyzed by fluorescent antibody cell sorting after labeling with dual color
      labeled antibody pairs. RESULTS: The pretreatment mean percentage of activated
      CD8+ T cells (DR+CD8+ T cells) was 12.23%, 16.72%, and 14.09% (Trials A, B, and
      C, respectively). Two weeks posttreatment, this increased to 22.87%, 26.15%, and
      39.04% (Trials A, B, and C, respectively), and these increases were statistically
      significant (p = 0.0188, p = 0.0010, p < 0.0001, respectively). The increase of
      DR+CD8+ T cells was significantly larger in Trial C than in Trial A (p = 0.0044)
      or Trial B (p = 0.0288). Total CD8+ T cells significantly increased at 2 weeks
      posttreatment in Trial B and C (p = 0.0013, p = 0.0004, respectively).
      Interestingly, only in Trial C were significant increases in activated CD4+ T
      cells seen at 2 weeks (p = 0.0035). CONCLUSIONS: This is the first report of
      systemic T-cell responses after HSV-tk+GCV/VCV gene therapy under three clinical
      trial conditions. There was an increase in activated CD8+ T cells in the
      peripheral blood after vector injection, suggesting the potential for activation
      of components of cell-mediated immune response in all trial conditions. The
      addition of radiotherapy to in situ gene therapy seems to further increase the
      total CD8+ T cells and activated CD4+ T cells.

PMID- 15145179
TI  - Adenoviral interleukin-3 gene-radiation therapy for prostate cancer in mouse
      model.
AB  - PURPOSE: The radiosensitizing effect of IL-3 gene therapy was evaluated on the
      syngeneic mouse prostate cancer model. METHODS AND MATERIALS: An adenoviral
      vector was used to deliver the mIL-3 alpha gene into syngeneic murine prostate
      (TRAMP-C1) cancer cells growing in a subcutaneous site and the tumor response to
      irradiation was assessed. RESULTS: Ad-mIL-3 gene therapy showed no tumor growth
      delay without radiation. However, intratumoral Ad-mIL-3 injection with radiation
      therapy showed marked tumor growth delay that was significantly greater than that
      of radiation alone. CONCLUSIONS: The combined intratumoral Ad-mIL-3 gene therapy
      and radiation therapy is a valuable option for further clinical evaluation.

PMID- 15145180
TI  - A forward-planned treatment technique using multisegments in the treatment of
      head-and-neck cancer.
AB  - PURPOSE: To describe in detail a forward-planned multisegment technique (FPMS) as
      an alternative treatment method for patients who are not suitable for inverse
      planned intensity-modulated radiation therapy (IP-IMRT), or for situations where
      IP-IMRT is not available in a medical clinic. METHODS AND MATERIALS: Between
      April 1995 and February 2002, 38 primary head-and-neck patients were treated
      using the FPMS technique, which has evolved over the past 7 years at our medical
      center. In the most recent version of the FPMS technique, which includes 5
      patients examined in this analysis, the primary tumor and the upper neck nodes
      were treated with 7 gantry angles, including an anterior, 2 lateral, 2 anterior
      oblique, and 2 posterior oblique beams with a total of 13 beam shapes formed by
      multileaf collimators (MLC), called MLC segments. The shape of each MLC segment
      was carefully designed, and the associated weights were optimized through manual
      iterations. The lower neck nodes and the supraclavicular nodes were treated with
      a split-beam anterior field, matched to the inferior border of the FPMS plan at
      the isocenter. With an autosequencing delivery system, all fields, including
      dynamic wedges, can be automatically treated. The dosimetric accuracy of this
      technique was verified with a phantom plan and measured with an ionization
      chamber, as well as film dosimetry. A sample FPMS plan is described in detail,
      and the average results for the 5 patients treated with FPMS are retrospectively
      compared to results for similar patients treated with IP-IMRT. RESULTS: The gross
      tumor volume was prescribed to 70 Gy (2.12 Gy/fraction) at the 88% isodose line,
      whereas the clinical target volume received a dose of 59.4 Gy (1.8 Gy/fraction)
      at the 75% isodose line. The maximum dose to the brainstem and spinal cord was
      below 54 and 45 Gy, respectively, comparable to IP-IMRT. The mean dose to the
      parotid glands was 32 Gy with FPMS vs. 26 Gy with IP-IMRT. Average delivery time
      was shorter for FPMS (15 min) than IP-IMRT (30 min), whereas the planning time
      depended on the expertise of the planner. Dosimetric accuracy for FPMS and IP
      IMRT plans using phantom measurements was similar, within 1% of the phantom plan.
      With a median follow-up of 31 months, there was no local-regional recurrence, and
      the incidence of xerostomia is reduced compared to conventional techniques.
      CONCLUSION: FPMS achieved plans comparable to those for IP-IMRT and is an ideal
      alternative treatment technique for a center without the capabilities of IP-IMRT
      or for a patient who is not a suitable candidate, because of prolonged treatment
      time. The treatment outcomes from our clinical experience indicate that FPMS can
      achieve excellent local freedom from progression rates without causing excessive
      toxicity. Lastly, IP-IMRT plans should be comparable to, if not better than, FPMS
      plans in the treatment of head-and-neck cancer.

PMID- 15145181
TI  - Online ultrasound image guidance for radiotherapy of prostate cancer: impact of
      image acquisition on prostate displacement.
AB  - AIM: Numerous studies reported the use of ultrasound image-guidance system to
      assess and correct patient setup during radiotherapy for prostate cancer. We
      conducted a study to demonstrate and quantify prostate displacement resulting
      from pressure of the probe on the abdomen during transabdominal ultrasound image
      acquisition for prostate localization. MATERIAL AND METHODS: Ten healthy
      volunteers were asked to undergo one imaging procedure. The procedure was
      performed in a condition that simulates the localization of prostate during
      online ultrasound guidance. A 3D ultrasound machine was used. The procedure
      started with the placement of the probe on the abdomen above the pubis symphysis.
      The probe was tilted in a caudal and posterior direction until the prostate and
      seminal vesicle were visualized. The probe was then fixed with a rigid arm, which
      maintained the probe in a static position during image acquisition. The probe was
      then moved, in a short time, stepwise toward the prostate, acquiring images at
      each step. The prostate and seminal vesicles were identified and selected in all
      planes. The first 3D volume was used as reference 1, to which all other scans
      were matched using a gray value matching algorithm. RESULTS: Prostate motion was
      quantified as a 3D translation relative to the patient coordinate system. The
      resulting translations represented the amount of prostate movement as a function
      of probe displacement. Between 7 and 11 images were obtained per volunteer, with
      a maximal probe displacement ranging between 3 and 6 cm. Prostate displacement
      was measured in all volunteers for all the probe steps and in all directions. The
      largest displacements occurred in the posterior direction in all volunteers. The
      absolute prostate motion was less than 5 mm in 100% of the volunteers after 1 cm
      of probe displacement, in 80% after 1.5 cm, in 40% after 2 cm, in 10% after 2.5
      cm, and 0% after 3 cm. To achieved a good-quality ultrasound images, the probe
      requires an average displacement of 1.2 cm, and this results in an average
      prostate displacement of 3.1 mm. No correlations were observed between prostate
      motion and prostate-probe distance or bladder size. CONCLUSION: Probe pressure
      during ultrasound image acquisition causes prostate displacement, which is
      correlated to the amount of probe displacement from initial contact. The induced
      uncertainty associated with this process needs to be carefully evaluated to
      determine a safe margin to be employed during online ultrasound image-guided
      radiotherapy of the prostate.

PMID- 15145182
TI  - A preliminary study of the role of modulated electron beams in intensity
      modulated radiotherapy, using automated beam orientation and modality selection.
AB  - PURPOSE: To develop an algorithm for optimal beam arrangement selection in
      intensity-modulated radiotherapy (IMRT) of mixed photon and electron beams. To
      apply this algorithm to study the utility of modulated electron beams in the
      context of IMRT planning. METHODS AND MATERIALS: The optimization algorithm
      selects, for a user-specified number of beams, the optimal IMRT arrangement (beam
      orientations, and photon/electron modality for each orientation) using a novel
      fast heuristic intensity modulation procedure. The algorithm was employed to
      select optimal beam arrangements for breast (two, four, and six axial beams) and
      head-and-neck (three, four, five, and seven nonaxial beams) cases. RESULTS: For
      the two cases, increasing the number of selected beams: (1) increased the number
      of electron beams for the breast case, but not more than one electron beam was
      selected for the head-and-neck case; (2) decreased critical structure doses for
      both cases; and (3) decreased target homogeneity for the breast case, but
      improved it for the head-and-neck case. CONCLUSIONS: In the two cases analyzed
      using the selection algorithm, the primary role of modulated electrons differs
      based on treatment site-normal tissue dose reduction in breast and target
      homogeneity improvement in head and neck. Although this preliminary study with
      two cases appears to suggest that the role of intensity-modulated electrons
      differs based on treatment site, further investigation of large numbers of cases
      and varied treatment sites are required to establish a definitive conclusion.

PMID- 15145184
TI  - Sphincter preservation in locally advanced rectal cancer due to the addition of
      continuous infusion 5-FU to preoperative radiation therapy or advances in
      surgical techniques?

PMID- 15145185
TI  - What does the black cat look like?

PMID- 15145186
TI  - Vascular endothelial growth factor serum level is strongly enhanced after burn
      injury and correlated with local and general tissue edema.
AB  - BACKGROUND: Burn associated local and general tissue edema is induced by local
      cell destruction and capillary leak syndrome. Vascular endothelial growth factor
      (VEGF) strongly enhances vascular permeability as well as angiogenesis. The
      principal aim of this study was to investigate the systemic release of VEGF and
      its kinetics after severe burn injury in humans. METHODS: Thirty-six burn
      patients and 42 healthy volunteers were enrolled in this study. Circulating VEGF
      serum levels were measured by enzyme-linked immunosorbent assay at days 1, 3, 7,
      14, 21, 28 and 35. Burn surface, tissue edema, complications and outcome were
      evaluated. RESULTS: VEGF serum levels were significantly increased after burn
      injuries immediately after injury until wound closure. VEGF levels reached their
      maximum at day 14 and were 22-fold increased compared to VEGF levels of healthy
      controls. After wound closure VEGF levels normalized. Local and general tissue
      edema disappeared after VEGF serum level normalization. CONCLUSIONS: VEGF serum
      levels are immediately enhanced after burn trauma until wound closure. At the
      same time, a local and general tissue edema was detected. We may speculate, that
      specific blockers of VEGF may have beneficial effects on edema and edema-related
      complications in severe burn patients.

PMID- 15145187
TI  - Skin blood flow pattern in burns outcomes.
AB  - Functional microcirculatory aspects of burned sites were examined including areas
      of self-healed burns, and grafted areas. Donor areas were also examined. In 10
      patients with burns in the lower limbs, both self-healed and with grafts, the
      microcirculatory response was evaluated by Laser Doppler flowmetry (LDF)
      measuring for each site the resting flux at 36 degrees, the postural venular
      arteriolar reflex (VAR) and the flux at 41 degrees (heating). The first
      evaluation was carried out on discharge, and subsequently at approximately 45 day
      intervals during uniform therapy follow-up (elastocompression). The burn-affected
      area (self-healed, graft) and those donor areas present should increase resting
      flux by comparison with control areas. This was particularly so in the self
      healed burn, which does however tend to converge in time towards control values.
      Response to stress tests (VAR and heating) presents percentage variations similar
      to normal skin in the various areas, with the exception of the grafted areas
      which present a reduced response in the 1st weeks following engraftment. No
      significant differences in response to heating were detected. It can be suggested
      that these differences are due to anatomic variations in revascularization and
      healing in the different areas as well as to alterations in microvascular
      innervation and local response to vasoactive substances.

PMID- 15145188
TI  - Increased norepinephrine production associated with burn injuries results in CCL2
      production and type 2 T cell generation.
AB  - The susceptibility of thermally injured mice (TI-mice) to various infections is
      markedly influenced by burn-associated type 2 T cell responses, which are common
      with severe thermal injuries. Previously, we have reported that CC chemokine
      ligand 2/monocyte chemoattractant protein-I (CCL2) is produced in mice within 1
      day of thermal injury, and the subsequent development of burn-associated type 2 T
      cell responses are triggered by this chemokine produced early after thermal
      injury. In this study, influence of norepinephrine (NE) on CCL2 production in
      mice early after thermal injury (TI) was investigated. Peripheral blood
      mononuclear cells (PBMC) and peritoneal macrophages (PMphi) from TI-mice produced
      CCL2, but the same cell preparations from normal mice did not. This chemokine was
      not produced by PBMC and PMphi from TI-mice previously treated with 6
      hydroxydopamine (6-OHDA), which destroys sympathetic nerve termini. NE production
      was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA
      resulted in the inhibition of NE secretion. When PBMC from normal mice were
      treated with NE, they acquired the ability to produce CCL2. Splenic T cells from
      TI-mice produced IL-4 into their culture fluids, while the cytokine was not
      produced by splenic T cells from TI-mice previously treated with 6-OHDA. These
      results indicate that NE may have an important role on early CCL2 production and
      the subsequent development of burn-associated type 2 T cell responses.

PMID- 15145189
TI  - Fibroblasts improve performance of cultured composite skin substitutes on athymic
      mice.
AB  - BACKGROUND: This study investigated the impact of adding human fibroblasts to a
      cultured composite skin substitute model of cultured human keratinocytes and
      acellular human dermis. METHODS: Skin substitutes were prepared by seeding human
      keratinocytes on the papillary side of acellular dermis with or without seeding
      fibroblasts on the reticular side. Performance of the grafts was compared both in
      vitro by histology and in vivo on surgically created full-thickness wounds on
      athymic mice. Graft size and contraction were measured and immunohistochemical
      stains were done to reveal vascularization. RESULTS: Skin substitutes with
      fibroblasts formed thicker epidermis than skin substitutes without fibroblasts.
      When transplanted onto athymic mice, skin substitutes with fibroblasts maintained
      their original size with only 2% contraction. In contrast, skin substitutes
      without fibroblasts showed 29% contraction. Vascular basement membrane specific
      mouse CD31staining and endothelial cell specific mouse collagen type IV staining
      revealed vascularization as early as 1 week posttransplant in grafts with
      fibroblasts, and was significantly higher than grafts without fibroblasts at 2
      weeks. CONCLUSIONS: Addition of fibroblasts to keratinocyte based composite skin
      substitutes improves epidermis formation, enhances vascularization and reduces
      contraction.

PMID- 15145190
TI  - Effects of cytokines and heat shock on defensin levels of cultured keratinocytes.
AB  - Burns have been associated with high levels of circulating pro-inflammatory
      cytokines which promote systemic inflammatory response syndrome (SIRS),
      immunosuppression and sepsis for which no effective treatment is currently
      available. Defensins, a family of cationic naturally occurring antimicrobial
      peptides, are considered important components of the innate immune system and
      enhance adaptive immunity. This study examines the effects of pro-inflammatory
      cytokines, interleukin-1beta (IL-1beta), gamma-interferon (IFNgamma) and tumor
      necrosis factor-alpha (TNFalpha) on human beta-defensin-2 (HBD-2) levels in
      cultured keratinocytes. We also examined the effects of heat shock at 42 degrees
      C. The results demonstrate that only TNFalpha shows significant induction of HBD
      2 but this induction was not sustained in the long-term. In addition, endogenous
      levels of defensin were significantly reduced by exposure to heat shock. The
      keratinocytes also responded to IL-1beta by becoming hypertrophic. These results
      indicate that stress-related, pro-inflammatory cytokines can induce keratinocytes
      to synthesize HBD-2, while heat shock appears to reduce its production. These
      experiments give us further insight into the role of natural antimicrobial
      peptides under conditions of stress.

PMID- 15145191
TI  - A dynamic study of the thermal components in electrical injury mechanism for
      better understanding and management of electric trauma: an animal model.
AB  - The thermal effects of acute electric trauma to living cells show some variation
      patterns and kinetics for different body components (muscle, bone, blood-vein and
      skin). Thermal energy transfer is random with no preferred directions, but
      electrical energy transfer is vectorial in the direction of the current. In the
      present study, a total 50 white male Wistar Albino rats, body weight 250-300 g,
      have been used to study electrical injury mechanism with subsequent change in
      muscle perfusion at different post-traumatic stages. The muscle temperature was
      found to increase with a sudden jump from 35.3+/-1.2 to 75.2+/-7.6 degrees C. The
      bone temperature increased from 35.2+/-1.4 to 45.8+/-1.2 degrees C and decayed
      slowly within 600+/-90 s. The venous blood curves show a similar pattern to that
      of muscle with a sudden jump of temperature from 36.4+/-.9 to 40.5+/-3.1 degrees
      C. The core temperature showed a flat pattern with a slight increase from 36.1+/
      0.8 to 37.3+/-0.6 degrees C and the peak temperature was found after 70+/-10 s.
      From the scintigraphic study, muscle perfusion was found to be a minimum 72 h
      after electric shock. The right hind limbs of all the rats (ground) exhibited
      more intense histopathological damages (electric burns) than the left fore limb
      (source).

PMID- 15145192
TI  - Incidence and patterns of childhood burn injuries in the Western Cape, South
      Africa.
AB  - The current study describes the epidemiology and patterns of moderate to severe
      childhood burn injuries in the Western Cape province in South Africa. Burn
      injuries sustained by children aged 12 years and younger and registered over
      January 1999 to December 2000 at the Red Cross Children's Hospital in the Western
      Cape are analysed (n=1201). Differences in risk distribution between different
      segments of the population are measured and typical injury patterns are
      identified. The results show that burn injury incidence is particularly high for
      toddlers (15.8/10000 child-years/c-y) and infants (14.6/10000 c-y) for boys
      (7.0/10000 c-y), and for African children (11.4/10000 c-y). Burn injury incidence
      is highest in winter (1.7/10000 c-y) but only significantly greater than the rate
      in summer (1.3/10000 c-y). Further, four burn injury patterns are identified, and
      labeled 'infant scalding', 'toddler scalding', 'injuries among older children
      with an over-representation of flame-related burns' and 'other causes of burns
      sustained to the head and neck region'. In sum, the risk of burn injury is higher
      in younger children. Differences between genders were more pronounced among
      younger and older age groups. Differences between population groups are more
      important in magnitude than in nature. The patterns identified can stimulate
      further research and development into the household product and environmental
      contributors to childhood burn injury.

PMID- 15145193
TI  - Mortality trends from burn injuries in Chile: 1954-1999.
AB  - OBJECTIVES: To study mortality trends due to burns in Chile. METHODS:
      Correlation, and descriptive study. Death reports from the Annals of Demography
      from 1954 to 1999, were analyzed and standardized rates of mortality by etiology,
      age and sex were calculated using regression models (Prais-Winsten) for each of
      them. Spearman's Rho test was used to show correlations (STATA 7.0). RESULTS:
      Linear reduction in burns rate (7.03-0.53) was found mainly because of a
      reduction in the pediatric group (15.3-2.4). The rate in the elder group showed a
      significant increase (4.28-11.03). The mortality rate due to chemical burns
      remained stable (1.4/1,000,000) and electrical burns showed an important increase
      since the 1990s (0.4-5.0/1,000,000). CONCLUSIONS: The decrease of the mortality
      rates due to burns, is mainly due to a large decrease in the pediatric group
      rates. Rates remained relatively stable for adults and increased in elders. The
      findings set a challenge to improve prevention campaigns and professional
      assessment and management in adults and elders.

PMID- 15145194
TI  - Changes of microbial flora and wound colonization in burned patients.
AB  - To determine time related changes of microbial colonization of burn wounds and
      body flora of burned patients, a prospective study was carried out. Fifty-one
      patients who were hospitalized at least 3 weeks were enrolled in the study.
      Periodic swabs were taken from burn wound, nasal, axillary, inguinal, and
      umbilical regions of the patients on admission and 7th, 14th, and 21st days of
      hospitalization. The mean body surface area burned was 22.9%. A total of 1098
      microbial isolates were detected during the study period. Coagulase-negative
      staphylococci (CNS, 63.0%) and Staphylococcus aureus (19.7%) were the most
      prevalent isolates in admission cultures. There was a gradual decrease in the
      number of isolates of CNS and a marked increase in the numbers of S. aureus and
      Pseudomonas aeruginosa from admission to 21st day. At the 21st day, the most
      frequent organisms were S. aureus (37.6%), CNS (34.7%), and P. aeruginosa
      (16.2%). Methicillin resistance of staphylococci strains were increased
      constantly in study period. While 35.3% of burn wounds were sterile on admission,
      microbial colonization reached 86.3% within the first week. Nasal carriage of
      methicillin resistant S. aureus increased from 3.9% to 62.7% at 21st day. The
      nature of microbial wound colonization and flora changes should be taken into
      consideration in empirical antimicrobial therapy of burned patients.

PMID- 15145195
TI  - Low Level Laser Therapy--a conservative approach to the burn scar?
AB  - Burn scars are known to be difficult to treat because of their tendency to worsen
      with hypertrophy and contracture. Various experimental and clinical efforts have
      been made to alleviate their effects but the problem has not been solved. Since
      patients keep asking for Low Level Laser Therapy (LLLT) and believe in its
      effectiveness on burn scars, and since former studies show contradictory results
      of the influence of LLLT on wound healing, this prospective study was designed to
      objectify the effects of LLLT on burn scars. Nineteen patients with 19 burn scars
      were treated with a 400 mW 670 nm Softlaser twice a week over 8 weeks. In each
      patient a control area was defined, that was not irradiated. Parameters assessed
      were the Vancouver Scar Scale (VSS) for macroscopic evaluation and the Visual
      Analogue Scale (VAS) for pruritus and pain. Photographical and clinical
      assessments were recorded in all the patients. Seventeen out of 19 scars
      exhibited an improvement after treatment. The average rating on the VSS decreased
      from 7.10+/-2.13 to 4.68+/-2.05 points in the treated areas, whereas the VSS in
      the control areas decreased from 6.10+/-2.86 to 5.88+/-2.72. A correlation
      between scar duration and improvement through LLLT could be found. No negative
      effects of LLLT were reported. The present study shows that the 400 mW 670 nm
      softlaser has a positive, yet sometimes limited effect on burn scars concerning
      macroscopic appearance, pruritus, and pain.

PMID- 15145196
TI  - Is high PEEP low volume ventilation in burn patients beneficial? A retrospective
      study of 61 patients.
AB  - In burn care lung damage by inhalation injury is a major cause of mortality in
      burn patients. In the field of intensive care medicine ventilation strategies to
      reduce lung injury caused by ventilation are under investigation. The promising
      results of the application of pressure controlled high PEEP low volume (HPLV)
      ventilation prompted us to use this ventilation strategy in our burn ICU. To
      establish whether this ventilation regime is beneficial the charts of 61
      consecutive patients needing artificial respiration were reviewed. A scoring
      system for PEEP level and tidal volume was developed and treatment groups with
      high PEEP and low volume and low PEEP high volume regimes were compared. No
      statistically significant differences could be found when comparing treatment
      versus mortality, the number of pulmonary complications or incidence of
      pneumothoraces. However, the trend showed a benefit in mortality for patients
      with an ABSI scoring up to 9, but at the same time pulmonary complications
      increase. The Horovitz oxygenation index showed no advantage for the HPLV Group.
      In a separate analysis we found a significant correlation between absolute PEEP
      and mortality. The correlation between PEEP level and mortality is a dynamic
      factor predicting outcome, This not been described yet and can be an addition to
      the static ABSI score. Differences between ventilation strategies were not as
      evident as expected in this retrospective study, so prospective randomized
      studies are needed.

PMID- 15145197
TI  - Experience with the seven flap-plasty for the release of burns contractures.
AB  - Eighteen patients with burns contracture to the knee 7 (34%), elbow 5 (28%),
      perineum 4 (22%), and axilla 2 (11%), were treated at our unit between February
      1998 to October 2001 using the seven flap-plasty. We chose this method because of
      its suitability for such contractures, which take the form of a web rather than a
      straight or linear pattern. Because it involves no donor area, that is no donor
      site morbidity and therefore less chance for longer hospital stay. The majority
      of these patients were children 11 (61%). Ten were females (56%) and 8 (44%) were
      males. Age of patients ranged between 2 and 35 years. The results of the
      procedure were satisfactory in all patients with good functional recovery of the
      affected sites.

PMID- 15145198
TI  - Split calvarial bone graft for chemical burn-associated nasal augmentation.
AB  - The nose is the central part of the face, and constitutes the most prominent
      projection in facial geometry. This report presents five cases that sustained a
      chemical burn injury with associated facial mutilation resulting from contact
      with strong acids. The chemical burn affected the nasal architecture after
      inflicting a burn injury to the face. Applying bone deriving from a split skull
      procedure for the nasal projection restoration and the augmentation of the dorsal
      nose is a feasible undertaking, and the overall result appears satisfactory. A
      retrospective survey of cases admitted to our clinic from January 1999 to
      December 2001, inclusively was undertaken and is described below. Split calvarial
      bone graft procedure for the nasal tip projection reconstruction was performed
      for five patients, all of whom had sustained chemical burns following assault by
      strong acid. The disfiguration of the nasal anatomical structure was due to
      healing from deep burn wounds. The tip became blunt and less protruberant
      following the arising of cicatricial tightness of the surrounding tissue.
      Strength and resistance to scar contraction are the first considerations for such
      implantation when attempting to correct the nasal tip projection. The five female
      patients sustained a severe chemical burn which involved a surface area ranging
      from 25 to 60% of total body surface area. The facial mutilation was noted
      simultaneously with the determination of the extent of the burning injury. A
      severe burn scar is the typical sequel following a deep chemical burn. Nasal tip
      projection was restored and a nasal dorsum augmentation procedure with a split
      calvarial bone graft under an "open" method was used. This particular surgical
      procedure was able to be used in order to improve the nasal tip projection and
      resist surrounding scar contracture. The three-dimensional surface structure of
      the face became more prominent subsequent to the administration of this
      procedure.

PMID- 15145199
TI  - Serum levels of vancomycin should be monitored in burn patients.

PMID- 15145200
TI  - Vancomycin acute anaphylactoid reaction in a paediatric burn.

PMID- 15145201
TI  - Critical care management of major hydrofluoric acid burns: a case report, review
      of the literature, and recommendations for therapy.

PMID- 15145202
TI  - Skin assessment of burn wounds covered with a collagen based dermal substitute in
      a 2 year-follow-up.

PMID- 15145203
TI  - Extrapyramidal symptoms following electrical burns--a case report.

PMID- 15145204
TI  - A fatal chemical burn associated with the industrial use of trichloroethylene
      vapour.

PMID- 15145205
TI  - Exercise caution!--a hazard of treadmills.

PMID- 15145206
TI  - Ex vivo expansion of hematopoietic cells.

PMID- 15145207
TI  - Ex vivo expansion of cord blood cells.

PMID- 15145208
TI  - Ex vivo expansion of umbilical cord blood hemopoietic stem and progenitor cells.

PMID- 15145209
TI  - Mesenchymal stem cells: paradoxes of passaging.
AB  - The field of stem cell biology continues to evolve with the ongoing
      characterization of multiple types of stem cells with their inherent potential
      for experimental and clinical application. Mesenchymal stem cells (MSC) are one
      of the most promising stem cell types due to their availability and the
      relatively simple requirements for in vitro expansion and genetic manipulation.
      Multiple populations described as "MSCs" have now been isolated from various
      tissues in humans and other species using a variety of culture techniques.
      Despite extensive in vitro characterization, relatively little has been
      demonstrated regarding their in vivo biology and therapeutic potential.
      Nevertheless, clinical trials utilizing MSCs are currently underway. The aim of
      this review is to critically analyze the field of MSC biology, particularly with
      respect to the current paradox between in vitro promise and in vivo efficacy. It
      is the authors' opinion that until this paradox is better understood, therapeutic
      applications will remain limited.

PMID- 15145210
TI  - Robust conversion of marrow cells to skeletal muscle with formation of marrow
      derived muscle cell colonies: a multifactorial process.
AB  - OBJECTIVE: Murine marrow cells are capable of repopulating skeletal muscle
      fibers. A point of concern has been the "robustness" of such conversions. We have
      investigated the impact of type of cell delivery, muscle injury, nature of
      delivered cell, and stem cell mobilizations on marrow-to-muscle conversion.
      METHODS: We transplanted green fluorescence protein (GFP)-transgenic marrow into
      irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin.
      One month after injury, sections were analyzed by standard and deconvolutional
      microscopy for expression of muscle and hematopoietic markers. RESULTS:
      Irradiation was essential to conversion, although whether by injury or induction
      of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected
      muscles showed significant number of GFP(+) muscle fibers, while uninjected
      muscles showed only rare GFP(+) cells. Marrow conversion to muscle was increased
      by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or
      GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice
      showed fusion of donor cells to recipient muscle. High numbers of donor-derived
      muscle colonies and up to 12% GFP(+) muscle cells were seen after mobilization or
      direct injection. These levels of donor muscle chimerism approach levels that
      could be clinically significant in developing strategies for the treatment of
      muscular dystrophies. CONCLUSION: In summary, the conversion of marrow to
      skeletal muscle cells is based on cell fusion and is critically dependent on
      injury. This conversion is also numerically significant and increases with
      mobilization.

PMID- 15145211
TI  - High-dose cyclophosphamide as salvage therapy for severe aplastic anemia.
AB  - OBJECTIVE: The treatment options for patients with aplastic anemia who do not
      respond to conventional immunosuppression are limited. The aim of this study was
      to evaluate high-dose cyclophosphamide in patients with refractory severe
      aplastic anemia (SAA). MATERIALS AND METHODS: We treated 17 SAA patients with
      high-dose cyclophosphamide (50 mg/kg/day for 4 consecutive days) who previously
      did not respond to one or more courses of immunosuppressive therapy. Median age
      was 31 years (range 6-58); median disease duration was 14 months (range 6-58),
      and 8 patients met criteria for very severe aplastic anemia (absolute neutrophil
      count <0.2 x 10(9)/L) at the time of treatment. RESULTS: At median follow-up of
      29 months, 10 patients (59%) are alive. Nine patients (53%) achieved a drug-free
      remission after high-dose cyclophosphamide; 4 patients achieved a complete
      remission and 5 patients currently meet criteria for a partial remission but
      continue to improve. One nonresponder to high-dose cyclophosphamide developed
      paroxysmal nocturnal hemoglobinuria; another nonresponder developed a
      myelodysplastic syndrome. In responding patients, median time to 500 neutrophils
      was 54 days (range 35-119), median time to the last platelet transfusion was 99
      days (range 51-751), and median time to the last red cell transfusion was 125
      days (range 63-796). CONCLUSION: High-dose cyclophosphamide shows promise for
      salvaging patients with refractory SAA.

PMID- 15145213
TI  - Codevelopment of dendritic cells along with erythroid differentiation from human
      CD34(+) cells by tumor necrosis factor-alpha.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) inhibits erythropoiesis and
      enhances nonerythroid colony formation. The present study examines the nature of
      these nonerythroid cells and investigates their physiologic role in relation to
      erythroid progenitor cells. MATERIALS AND METHODS: Highly purified human CD34(+)
      cells underwent erythroid differentiation in the presence of multiple cytokines,
      including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO),
      with and without TNF-alpha. We enumerate colony-forming unit-erythroid (CFU-E)
      and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells
      in semisolid phase as well as in liquid suspension culture. The character and
      roles of codeveloping nonerythroid cells in the presence of TNF-alpha were
      analyzed using fluorescent activating cell sorter, enzyme immunohistochemistry,
      and confocal microscopy. RESULTS: TNF-alpha inhibited the generation of GPA(+)
      cells and conversely enhanced the generation of GPA(-) cells. The GPA(-) cells
      were comprised of cells with excentric cell shape and were positive for HLA class
      I, HLA class II, CD1a, CD4, CD11c, CD14, CD40, CD80, CD83, and CD86, but not for
      CD3, CD8, CD19, CD20, and CD56, indicating the codevelopment of dendritic cells
      (DC) along with erythroid differentiation. Developing DC/DC precursors were
      detected within 3 days of culture. Only in the presence of TNF-alpha did CD34(+)
      cells proliferate by forming aggregates where both GPA(+) and CD11c(+) DC/DC
      precursors were present. During culture period, immature CD11c(+) DC were capable
      of endocytosing damaged GPA(+) cells. CONCLUSIONS: GPA(-) cells cogenerated from
      human CD34(+) cells during erythroid differentiation in the presence of IL
      3/SCF/EPO and TNF-alpha express DC phenotypes. The CD11c(+) DC subset physically
      and selectively associates with developing immature erythroid cells and damaged
      self-GPA(+) cells and then obtains and captures self-substances.

PMID- 15145212
TI  - Enhanced circulating half-life and hematopoietic properties of a human
      granulocyte colony-stimulating factor/immunoglobulin fusion protein.
AB  - OBJECTIVE: The aim of this study was to determine whether fusion proteins
      comprising human granulocyte colony-stimulating factor (G-CSF) joined to human
      immunoglobulin G1 and G4 (IgG1 and IgG4) Fc and C(H) domains are biologically
      active and have improved pharmacokinetic and hematopoietic properties in vivo.
      MATERIAL AND METHODS: Chimeric genes encoding human G-CSF fused to the N-termini
      of the Fc and C(H) domains of human IgG1 and IgG4 were constructed and used to
      transfect monkey COS cells. The fusion proteins were purified from the
      conditioned media by protein A affinity chromatography. Bioactivities of the
      proteins were measured in a G-CSF-dependent in vitro bioassay. Pharmacokinetic
      and granulopoietic properties of the G-CSF/IgG1-Fc fusion protein were measured
      in normal rats. RESULTS: The G-CSF/IgG-Fc and G-CSF/IgG-C(H) fusion proteins were
      secreted from transfected COS cells primarily as disulfide-linked homodimers. On
      a molar basis, the purified G-CSF/IgG-Fc fusion proteins were as active as G-CSF
      in in vitro bioassays, whereas bioactivities of the purified G-CSF/IgG-C(H)
      fusion proteins were decreased 3- to 4-fold. The G-CSF/IgG1-Fc fusion protein
      displayed a slower plasma clearance rate and stimulated greater and longer
      lasting increases in circulating neutrophils and white blood cells than G-CSF
      following intravenous and subcutaneous administration to rats. CONCLUSION: Fusion
      of G-CSF to human IgG domains results in homodimeric fusion proteins possessing
      high in vitro bioactivities, long circulating half-lives, and enhanced
      hematopoietic properties in vivo.

PMID- 15145215
TI  - Small peptide analogs to stromal derived factor-1 enhance chemotactic migration
      of human and mouse hematopoietic cells.
AB  - Stromal cell-derived factor 1 (SDF-1) is a chemokine that binds to the CXCR4
      receptor. Its functions include acting as a chemotactic factor for hematopoietic
      stem and progenitor cells. We recently reported the synthesis of a small cyclized
      peptide analog (31 amino acids) of the terminal regions of SDF-1 that had
      biological function comparable to the native molecule (67 amino acids). In the
      present study, we investigated the effects of SDF-1 analogs (CTCE0021 and
      CTCE0214) in the chemotactic migration of peripheral blood hematopoietic cells
      (lineage-negative and CD34(+) cells). Enhanced chemotaxis of normal and G-CSF
      mobilized hematopoietic cells was observed with both SDF-1 analogs in a dose
      dependent manner. The increases were statistically significant (p < or = 0.016 by
      one-way ANOVA) at analog concentrations of 50 to 100 microg/mL. Colony-forming
      progenitor cells were not affected by exposure to the analogs up to 100
      microg/mL. When different doses of the SDF-1 analog CTCE0214 were administered to
      mice, significant increases in circulating hematopoietic cells (identified by
      flow cytometry as lineage(low/-), Sca-1(+), and c-kit(+)) were observed after a
      single injection of 75 microg per animal. The effect was apparent at 4 hours and
      became significant at 24 hours. These results suggest that SDF-1 analogs can be
      considered for mobilization of hematopoietic stem cells.

PMID- 15145214
TI  - Expression of an anti-sickling beta-globin in human erythroblasts derived from
      retrovirally transduced primitive normal and sickle cell disease hematopoietic
      cells.
AB  - OBJECTIVE: Recent improvements in human beta-globin vector design have fueled
      interest in gene therapy approaches to the treatment of human thalassemia and
      sickle cell disease (SCD). The present study was undertaken to determine whether
      human beta-globin mRNA and protein could be obtained in the erythroid progeny of
      more primitive human target cells transduced with a retrovirus containing murine
      stem cell virus long terminal repeats, a phosphoglycerate kinase promoter driving
      the expression of a green fluorescence protein (GFP) cDNA, and an anti-sickling
      beta-globin (beta87(+)) gene under the control of an HS2, HS3, HS4 enhancer
      cassette. MATERIALS AND METHODS: A two-step pseudotyping strategy was devised to
      obtain useful preparations of this virus. Primitive cells present in normal human
      cord blood (CB) and adult SCD patients' blood samples were infected and the level
      of gene transfer (% GFP(+) cells) and erythroid-specific beta87(+)-globin
      expression assessed. RESULTS: Analysis of the proportion of infected cells that
      became GFP(+) showed that this virus transduced approximately 50% of initial
      CD34(+) CB and SCD cells and up to 23% of cells able to regenerate both lymphoid
      and myeloid cells in sublethally irradiated primary and secondary NOD/SCID mice.
      beta87(+)-globin transcripts were readily detected in erythroblasts generated
      from primitive transduced CB cells and SCD progenitors. Evidence of beta87(+)
      derived protein in transduced CB cell-derived erythroblasts also was obtained.
      CONCLUSION: These findings demonstrate that retroviral vector-based gene transfer
      approaches can be used to achieve human beta-globin protein expression in the
      erythroid progeny of transplantable human precursors.

PMID- 15145216
TI  - Identification of genes differentially regulated by the P210 BCR/ABL1 fusion
      oncogene using cDNA microarrays.
AB  - OBJECTIVE: The t(9;22) translocation is associated with more than 95% of cases of
      chronic myeloid leukemia. The resulting fusion of the BCR and ABL1 loci produces
      the constitutively active BCR/ABL1 tyrosine kinase. A wide range of signal
      transduction molecules are activated by BCR/ABL1, including MYC, PI-3 kinase, and
      different STAT molecules. In contrast, relatively few genes are known to be
      regulated by BCR/ABL1 at the level of transcription. MATERIALS AND METHODS: In an
      effort to better understand the transcriptional program activated by BCR/ABL1, we
      used cDNA microarrays to evaluate the relative expression of approximately 6450
      human genes in U937 myelomonocytic cells expressing P210 BCR/ABL1 via a
      tetracycline-inducible promoter. RESULTS: We confirmed the previously reported up
      regulation of the PIM1 and JUN oncogenes by BCR/ABL1. In addition, we identified
      59 more genes up-regulated by BCR/ABL1. Interestingly, roughly one third of these
      were genes previously reported to be interferon (IFN)-responsive, including the
      OAS1, IFIT1, IFI16, ISGF3G, and STAT1 genes. An additional seven BCR/ABL1
      regulated genes were found to be IFN-responsive in U937 cells. The expression
      profile also included genes encoding transcription factors, kinases, and signal
      transduction molecules, as well as genes regulating cell growth, differentiation,
      apoptosis, and cell adhesion, features previously suggested to be affected by
      BCR/ABL1. CONCLUSION: These observations shed novel insight into the mechanism of
      BCR/ABL1 action and provide a range of targets for further investigation.

PMID- 15145217
TI  - Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease
      differ phenotypically and functionally from normal and suggest distinct
      subpopulations that generate F cells.
AB  - OBJECTIVE: Sickle cell disease (SCD) is remarkable for stress erythropoiesis. We
      investigated the progenitor populations contributing to erythroid stress.
      MATERIALS AND METHODS: We characterized hematopoietic progenitor cells in sickle
      bone marrow and sickle peripheral blood from patients with SCD compared to those
      in normal bone marrow. RESULTS: There were increased proportions of sickle bone
      marrow and sickle peripheral blood CD34(+) cells that coexpressed glycophorin A
      (GlyA), normally expressed late during erythroid differentiation when CD34 is
      down-regulated. Remarkably, increased numbers of CD34(+)CD38(-) hematopoietic
      progenitor cells from sickle bone marrow (p < 0.03) and sickle peripheral blood
      (p < 0.004) coexpressed GlyA, compared to normal bone marrow CD34(+)CD38(-)
      hematopoietic progenitor cells. At a molecular level, even the sickle bone marrow
      and sickle peripheral blood CD34(+)CD38(-) hematopoietic progenitor cells not
      expressing GlyA by fluorescence-activated cell sorting or reverse transcriptase
      polymerase chain reaction expressed the erythroid-specific gene GATA-1, unlike
      normal bone marrow, suggesting desynchronized erythroid gene expression in the
      SCD hematopoietic progenitor cells. We also generated red blood cells in vitro
      from GlyA(+) and GlyA(-)CD34(+) cells. GlyA(+)CD34(+) produced more F cells (p <
      0.02) and had lower clonogenicity (p < 0.01) and erythroid expansion potential.
      Increased F cells were generated only from sickle CD34(+) hematopoietic
      progenitor cells (p < 0.04), as occurs in vivo. CONCLUSION: Stress erythropoiesis
      in SCD has been postulated to accelerate erythropoiesis and production of F
      cells. Thus, CD34(+)CD38(-) expressing GlyA may represent the "stress progenitor"
      population. This is the first study characterizing CD34(+) and CD34(+)CD38(-)
      hematopoietic progenitor cells in sickle bone marrow, comparing them to sickle
      peripheral blood and normal bone marrow and using them to generate sickle red
      blood cells that recapitulate F cell production observed in vivo. We identified a
      unique population of GlyA(+)CD34(+) cells in SCD, which is in an accelerated
      erythroid differentiation pathway, has not down-regulated CD34 antigen
      expression, and predominantly generates F cells.

PMID- 15145218
TI  - Studies of the route of administration and role of conditioning with radiation on
      unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman
      primate model.
AB  - OBJECTIVE: The aim of this study was to examine the effects of the route of
      administration [intrabone marrow (IBM) vs intravenous (IV)] and the role of
      conditioning with irradiation in optimizing mesenchymal stem cell (MSC)
      transplantation. MATERIALS AND METHODS: To determine if irradiation resulted in
      depletion of colony-forming unit fibroblasts (CFU-F), which might favor the
      engraftment of donor MSC, the number of CFU-Fs was assayed from animals receiving
      either hemibody irradiation (HBI) or total body irradiation (TBI). RESULTS: TBI
      resulted in a marked reduction of CFU-F numbers that spontaneously resolved,
      whereas animals receiving HBI did not experience depletion of CFU-F. Animals
      receiving MSC grafts by the IV route had higher numbers of marrow CFU-F. MSC were
      transduced using retroviral vectors encoding the neomycin resistance gene
      (Neo(R)) and a second gene encoding either the human soluble tumor necrosis
      factor receptor (hsTNFRII) or beta-galactosidase (beta-Gal). MSCs were
      administered by either the IV or IBM route to animals receiving HBI. The Neo(R)
      transgene was detectable in hematopoietic tissues of all animals and
      nonhematopoietic tissues in a single animal. Evidence of transgene expression was
      documented by detection of beta-Gal(+) cells in BM smears and transiently
      elevated serum levels of hsTNFRII. CONCLUSION: These studies indicate that 1) MSC
      possess the ability to engraft and persist in an unrelated mismatched allogeneic
      hosts; 2) 250-cGy HBI did not favor engraftment of MSC; 3) the IBM route was not
      more effective than the IV route in delivering MSC grafts; and 4) transplanted
      MSC preferentially localized to the marrow rather than nonhematopoietic tissues.

PMID- 15145219
TI  - Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells in
      pellet cultural system.
AB  - OBJECTIVE: Pluripotent mesenchymal stem cells (MSC) have been isolated and well
      characterized from several tissue sources, including bone marrow stroma. MSC from
      different animals showed slight differences in morphology and in the potential to
      differentiate. In the present study, we isolated MSC from bovine bone marrow and
      induced chondrogenesis in order to establish a new experimental model of stem
      cell research. METHODS: Bone marrow was harvested from 8 calves. For inducing
      chondrogenesis, MSC were cultured in pellet culture system in a chemically
      defined medium supplemented with 0 and 10 ng/mL of transforming growth factor
      beta1 (TGF-beta1). Chondrogenic differentiation was evaluated by histological,
      immunohistochemical, and in situ hybridization techniques. The degrees of genes
      expression were measured by quantitative RT-PCR. RESULTS: Metachromatic alcian
      blue staining and immunoreactivity for type II collagen were detected in both
      pellet groups (0 and 10 ng/mL TGF-beta1) after 7 days of culturing. In situ
      hybridization demonstrated strong expression of type II collagen and aggrecan
      mRNAs in the round cells located at the center region of pellets and at densely
      organized areas. On the other hand, type I collagen mRNA was strongly expressed
      in the superficial layer of the pellets. After 20 days of pellet culture,
      expression of type II collagen mRNA in the cells which were not treated by TGF
      beta1 was 1.7-fold higher compared with that treated by TGF-beta1. CONCLUSION:
      Independent, spontaneous chondrogenesis of bovine MSC in pellet culture occurred
      without addition of any external bioactive stimulators, namely factors from TGF
      beta family, which were previously considered necessary.

PMID- 15145220
TI  - Kinetic analysis of uranium accumulation in the bivalve Corbicula fluminea:
      effect of pH and direct exposure levels.
AB  - The bioaccumulation of natural uranium in the freshwater bivalve Corbicula
      fluminea was investigated subsequent to the bivalve's experimental waterborne
      exposures. A first experiment determined the accumulation rate (transfer
      efficiency, tissular distribution) and subcellular distribution of uranium in
      organs after over 42 days of uranium exposure (100 microg l(-1); pH 7) and later
      following 60 days of depuration. Results showed that there was direct transfer of
      uranium to the bivalve organs ([U]organism/[U]water = 0.16, fresh weight, fw).
      The highest accumulation levels occurred in the visceral mass and remained
      constant throughout the exposure duration, although a linear increase in the U
      concentration in the gills was observed (2.98 +/- 1.3-10.9 +/- 3.7 microg g(-1)
      between days 2 and 42). A second set of experiments were performed in order to
      test the influence of the exposure levels (100; 500; 1500 microg l(-1)) and pH (7
      and 8.1) on the bioaccumulation capacities. A marked difference of U distribution
      is observed as a function of exposure levels (gills were favoured in the case of
      high exposure levels-relative burden: 49.1 +/- 3% (1500 microg l(-1)), whereas
      the visceral mass presented higher accumulation levels at environmentally
      relevant U concentrations). Uranium concentration in the insoluble fraction (80%)
      in the whole body does not depend upon exposure levels in the water column or
      upon duration. These experiments did not allow any link to be established between
      the free-metal ion concentration and the bioaccumulation efficiency. Results
      showed a significant pH effect and indicated a link between the exposure
      conditions and the distribution of uranium in the bivalve organs.

PMID- 15145221
TI  - 17-Beta estradiol and 4-nonylphenol delay smolt development and downstream
      migration in Atlantic salmon, Salmo salar.
AB  - The effect of 17-beta estradiol (E2) and 4-nonylphenol (4-NP) on smoltification
      and downstream migration of Atlantic salmon was studied in an integrated
      laboratory and field study. In a stock of hatchery-raised 1-year-old salmon,
      smoltification progressed from February until late May as judged by increased
      gill Na+, K+ -ATPase activity and 24 h sea water (SW)-tolerance. Starting late
      March, three groups of 150 fish were each given 6 serial injections over 20 days
      of 2 microg/g body weight E2, 120 microg/g 4-NP dissolved in peanut oil or peanut
      oil (4 microl/g) as control. After the last injection, all fish were individually
      tagged (Passive Integrated Transponder tags) and a non-lethal gill biopsy was
      taken. Two days later (8 April), 100 fish per group were transported to the field
      site and released into a small stream. Smolt migration was registered by
      measuring arrival time at a trap downstream of the release site. Serum
      vitellogenin levels increased several-fold in both male and female E2- and 4-NP
      treated fish. Overall, E2- and 4-NP-treatment impaired smolting as judged by
      elevated condition factor, reduced gill Na+, K+ -ATPase activity and alpha
      subunit Na+, K+ -ATPase mRNA level, reduced muscle water content and increased
      mortality following 24 h SW-challenge. After release, control fish initiated
      downstream migration immediately, with 50% of the total number of migrants
      appearing in the trap within 10 days. E2- and 4-NP-treated fish appeared in the
      trap with a delay in comparison to controls of 6 and 8 days, respectively. After
      the smolt run, no fish were registered by electro-fishing upstream of the trap.
      The total number of fish reaching the trap and thus post-release survival was in
      the order control (81%), E2 (53%), 4-NP (12%). Representatives from all treatment
      groups held under simulated natural conditions in the laboratory survived 100%
      through the migration period, suggesting that a combination of behavioural and in
      stream factors (predation by herons) may contribute to the differential
      mortality. The study indicates that short-term exposure to natural and
      environmental estrogens may impair smolt development and survival and delay
      subsequent downstream migration in Atlantic salmon.

PMID- 15145222
TI  - Relationship between uptake capacity and differential toxicity of the herbicide
      atrazine in selected microalgal species.
AB  - Microalgal species vary in their sensitivity to the triazine herbicide, atrazine.
      This study examined both atrazine uptake and cellular characteristics of
      microalgae to determine if either can be used to predict algal sensitivity.
      Standard toxicity tests were performed on five microalgal species, each
      representing a different algal division or habitat. Test species listed in order
      of increasing sensitivity were: Isochrysis galbana, Dunaliella tertiolecta,
      Phaeodactylum tricornutum, Pseudokirchneriella subcapitata, and Synechococcus sp.
      Each species was exposed to 14C-atrazine at its growth rate EC50 concentration
      (44-91 microg/L). At five time-points over 96 h, samples were filtered to collect
      algae and washed with unlabeled atrazine to displace labeled atrazine loosely
      absorbed to the cell surface. Radioactivity present on filters and in the growth
      medium was measured by liquid scintillation counting. Relationships between algal
      species-sensitivity to atrazine and compound uptake, cell dry weight, cell
      volume, and cell surface area were determined by linear regression analysis. Cell
      size measurements (based on dry weight, biovolume, and surface area) were
      significantly correlated with atrazine uptake (R2 > 0.45, P-value < 0.05). There
      was a significant correlation between atrazine uptake and species-sensitivity to
      atrazine (R2 = 0.5413 , P-value = 0.0012). These results indicate that smaller
      cells with greater surface area to volume ratios will incorporate more atrazine,
      and in general, will be more sensitive to atrazine exposure. However, I. galbana,
      with small cell size and relatively high atrazine uptake was the least sensitive
      species tested. This species and others may have mechanisms to compensate for
      atrazine stress that make predicting responses of microalgal communities
      difficult.

PMID- 15145223
TI  - Some polybrominated diphenyl ether (PBDE) flame retardants with wide
      environmental distribution inhibit TCDD-induced EROD activity in primary cultured
      carp (Cyprinus carpio) hepatocytes.
AB  - Ethoxyresorufin-O-deethylase (EROD) activity, a catalytic function of the
      cytochrome P450 1A (CYP1A) microsomal oxygenase subfamily, is a popular biomarker
      for exposure to xenobiotics, polyhalogenated aromatic hydrocarbons (PHAHs) in
      particular. It has found wide use in aquatic pollution assessment both in vivo
      and in vitro. In such studies, subjects are often exposed to complex mixtures
      where various constituents can interfere with EROD-activity, possibly resulting
      in inadequate estimation of toxic hazard or biological response. The present
      study investigates the effects of polybrominated diphenyl ethers (PBDEs), a
      relatively new and increasingly detected group of environmental contaminants, on
      the validity of EROD activity as exposure marker in carp (Cyprinus carpio)
      hepatocytes. Freshly isolated hepatocytes of a genetically uniform strain of male
      carp were co-exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at
      concentrations of 0, 1, 3, 10, 30, and 100 pM, and one of the highly purified
      PBDE/PCB congeners (at concentrations of 0, 0.25, and 2.5 microM) or cleaned-up
      and untreated DE-71 samples (0, 0.1, and 1 microM). PBDEs were selected from the
      209 possible congeners based on their relative abundance in environmental
      samples: BDE-47, BDE-99, BDE-100, and BDE-153. A tentative metabolite of BDE-47,
      6OH-BDE-47, was also included. In addition, a commercial pentabrominated
      dipenylether mixture (DE-71) was tested for interference with EROD activity both
      with and without clean-up by carbon fractionating which removed possible planar
      contaminants. Polychlorinated biphenyl (PCB)-153, a reported inhibitor of EROD
      activity in flounder, was included for comparison. Cells were cultured for a
      total period of 8 days; exposure started at day 3 after cell isolation. After 5
      days of exposure, cell pellets were frozen before EROD activity was determined.
      Upon exposure to TCDD, the cells responded with increased EROD activity as
      expected. Significant reduction of TCDD-induced EROD activity was found in the
      presence of BDE-47, BDE-99, and BDE-153, but not with BDE-100 and 6-hydroxylated
      BDE-47. Of these PBDE congeners, the most abundant congener in environmental
      samples, BDE-47, exhibited the strongest inhibition (down to 6% of the TCDD
      control value). The cleaned-up fraction of commercial penta-BDE (DE-71) mixture
      proved an even more potent inhibitor, resulting in reduction of EROD activity to
      4% of the control values observed at 1.0 microM. BDE-47 and BDE-153 did not
      reduce TCDD-induced EROD activity when added shortly prior to measurement,
      suggesting possible interaction with TCDD at the level of CYP1A biosynthesis. PCB
      153 did not show significant effects on EROD activity in carp in this study. The
      present results indicate that environmentally relevant PBDEs can interfere with
      determination of EROD activity in vitro, at levels reported earlier for PCBs. The
      observation that detected PBDE levels are rising, stresses the need for caution
      when interpreting EROD data on environmental samples.

PMID- 15145224
TI  - Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I:
      histopathological alterations and bioaccumulation in rainbow trout.
AB  - Human and veterinary pharmaceuticals have been shown to occur in considerably
      high amounts in sewage treatment plant (STP) effluents and surface waters. The
      non-steroidal inflammatory drug diclofenac represents one of the most commonly
      detected compounds. Information concerning possible ecotoxicological risks of the
      substance are rather scarce. So far there are no data available on its possible
      effects in fish after prolonged exposure. In order to evaluate sublethal toxic
      effects of diclofenac in fish, rainbow trout (Oncorhynchus mykiss) exposed to
      diclofenac concentrations ranging from 1 microg/L to 500 microg/L over a 28 day
      period were investigated by histopathological methods. In addition, diclofenac
      residues in various organs were analyzed by means of gas chromatography/mass
      spectrometry (GC/MS). The histopathological examinations of diclofenac-exposed
      fish revealed alterations of the kidney such as an hyaline droplet degeneration
      of the tubular epithelial cells and the occurrence of an interstitial nephritis.
      In the gills, the predominant finding consisted in a necrosis of pillar cells
      leading to damage of the capillary wall within the secondary lamellae. The lowest
      observed effect concentration (LOEC) at which both renal lesions and alterations
      of the gills occurred was 5 microg/L. In contrast, the light microscopical
      examination of the liver, the gastro-intestinal tract, and the spleen did not
      reveal any histopathological alterations neither in diclofenac-exposed fish nor
      in solvent controls or control individuals. Chemical analysis showed a
      concentration-related accumulation of diclofenac in all organs examined. The
      highest amounts could be detected in the liver, followed by the kidney, the gills
      and the muscle tissue. Dependent on the diclofenac concentration used, the
      bioconcentration factors (BCF) were 12-2732 in the liver, 5-971 in the kidney, 3
      763 in the gills, and 0.3-69 in the muscle respectively. From the present
      findings it can be assumed, that prolonged exposure in environmentally relevant
      concentrations of diclofenac leads to an impairment of the general health
      condition of fish.

PMID- 15145225
TI  - Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part II:
      cytological effects in liver, kidney, gills and intestine of rainbow trout
      (Oncorhynchus mykiss).
AB  - In the present study, cytopathology was investigated in the liver, kidney, gills
      and gut of rainbow trout (Oncorhynchus mykiss) exposed to five different
      concentrations (1, 5, 20, 100 and 500 microg/L) of the anti-inflammatory drug
      diclofenac under laboratory conditions. The lowest observed effect concentration
      (LOEC) for cytological alterations in liver, kidney and gills was 1 microg/L. In
      the gut, however, no diclofenac-induced cytopathology occurred. As the most
      prominent reactions induced by diclofenac (1) in the kidney, a severe
      accumulation of protein in the tubular cells (so called hyaline droplet
      degeneration), macrophage infiltration and structural alterations (dilation,
      vesiculation) of the endoplasmic reticulum (ER) in the proximal and distal renal
      tubules were observed. Furthermore, shortening of podocytes and their retraction
      from the basal lamina, a thickening of the basal lamina, the formation of
      desmosomes, and necrosis of endothelial cells in the renal corpuscles occurred;
      (2) in the liver, the most striking reactions were the collapse of the cellular
      compartmentation as well as the glycogen depletion of hepatocytes; (3) in the
      gills, pillar cell necrosis, hypertrophy of chloride cells, and epithelium
      lifting became evident in the secondary lamellae.

PMID- 15145226
TI  - Time-course variations of oxyradical metabolism, DNA integrity and lysosomal
      stability in mussels, Mytilus galloprovincialis, during a field translocation
      experiment.
AB  - Harbours can be considered as model environments for developing and validating
      field monitoring procedures and to investigate mechanistic relationships between
      different biological responses. In this study, several biomarkers were
      investigated in marine mussels caged for 4 weeks into an industrialised harbour
      of north-west Italy. Organisms were collected at different time intervals to
      better characterise the sensitivity, temporal variations and interactions of
      analysed responses. Besides single antioxidants (catalase, glutathione S
      transferases, glutathione reductase, total glutathione), the total oxyradical
      scavenging capacity (TOSC) assay was used to analyse the capability of the whole
      antioxidant system to neutralise specific forms of radicals: these data were
      further integrated by measurement of DNA integrity, oxidised bases and the
      impairment of lysosomal membrane stability in haemocytes. Results showed a
      biphasic trend for single antioxidants and TOSC, with no variation or increase
      during the first 2 weeks of exposure to the polluted site followed by a
      progressive decrease up to a severe depletion in the final part of the
      experiment. These findings suggest an initial counteractive response of mussels
      toward the enhanced prooxidant challenge, while antioxidants appeared overwhelmed
      at longer exposure periods. The hypothesis of reactive oxygen species (ROS)
      mediated toxicity is supported by the appearance of cell damages (DNA integrity
      and lysosome membrane stability), which exhibited a progressive enhancement
      during the course of the experiment with a maximum impairment after 30 days of
      exposure.

PMID- 15145227
TI  - An unexpected parallelism between Vitamin A and PCBs in seal milk.
AB  - Bioaccumulating pollutants such as polychlorinated biphenyls (PCBs) induce a
      range of adverse effects in mammals. Vitamin A metabolism is prone to such
      pollutant disruption which may be particularly harmful for young animals. During
      lactation, maternal PCBs are transferred to the offspring through the milk. Seal
      milk is very fatty and consequently contains large amounts of these persistent
      lipophilic contaminants. In the present study, we investigated the relationships
      between PCBs and Vitamins A and E during lactation, in free-ranging grey seals,
      using longitudinal samples of milk and blubber. We discovered that, unlike
      Vitamin E or triglycerides, the dynamics of Vitamin A matches closely those of
      PCBs in milk throughout lactation. Levels of Vitamin A and PCBs remain constant
      during the first half of lactation and then increase at late lactation,
      indicating that pups ingesting higher levels of PCBs also ingest higher amounts
      of Vitamin A.

PMID- 15145229
TI  - Unilateral neck exploration for primary hyperparathyroidism.
AB  - Focused unilateral cervical exploration is a controversial alternative to
      conventional bilateral neck exploration for primary hyperparathyroidism (HPT) due
      to solitary adenoma. Development of preoperative localization techniques, notably
      isotope scintigraphy and small-part, real-time ultrasonography, has increased
      preoperative parathyroid tumor identification. Critics of scan directed
      unilateral neck exploration argue it may overlook enlarged parathyroid glands on
      the unexplored side, increasing the incidence of persistent and recurrent
      hypercalcemia. Our experience of this operation and prolonged follow-up of
      patients, however, confirm that it does not increase risk of persistent or
      recurrent HPT if a strict selection protocol is observed. This ensures the
      confident further development of minimally invasive surgical procedures for HPT
      based on the principle of a focused exploration following preoperative
      localization of the parathyroid adenoma.

PMID- 15145228
TI  - Anatoxin-a elicits an increase in peroxidase and glutathione S-transferase
      activity in aquatic plants.
AB  - Although the toxic effects of cyanotoxins on animals have been examined
      extensively, little research has focused on their effects on macrophytes and
      macroalgae. To date only microcystins have been found to be detrimental to
      aquatic plants. Peroxidase activity of the free floating aquatic plant Lemna
      minor and the filamentous macroalga Chladophora fracta was measured after
      exposure to several concentrations of the cyanotoxin, anatoxin-a. Peroxidase
      activity (POD) was significantly (P < 0.05) increased after 4 days of exposure to
      an anatoxin-a concentration of 25 microg mL(-1) for both L. minor and C. fracta.
      Peroxidase activity was not significantly increased at test concentrations of 15
      microg mL(-1) or lower. In another experiment, the effects of various
      concentrations of anatoxin-a on the detoxication enzyme, glutathione S
      transferase (GST) in L. minor were investigated. GST activity was significantly
      elevated at anatoxin-a concentrations of 5 and 20 microg mL(-1). Photosynthetic
      oxygen production by L. minor was also found to be reduced at these
      concentrations. This is the first report to our knowledge of the cyanotoxin
      anatoxin-a being harmful to aquatic plants.

PMID- 15145230
TI  - Minimal-access/minimally invasive parathyroidectomy for primary
      hyperparathyroidism.
AB  - Minimal-access or minimally invasive parathyroidectomy is replacing a bilateral
      neck exploration as the surgical approach of choice in primary
      hyperparathyroidism (pHPT). When a parathyroid adenoma is localized
      preoperatively, ideally with sestamibi combined with ultrasonography, results
      equivalent to a bilateral neck exploration can be achieved through an incision
      less than 2.5 cm. Minimal-access techniques offer the advantage of cure under
      local anesthesia with a smaller incision and no overnight stay. Intraoperative
      measurement of parathyroid hormone (PTH) may be a valuable adjunct to
      confirmation of parathyroid adenoma removal, but currently appears to add little
      when preoperative localization is optimized. Controlled studies and long-term
      follow-up will be required to establish the true value of parathyroid minimal
      access surgery.

PMID- 15145231
TI  - Minimally invasive, video-assisted thyroidectomy (MIVAT).
AB  - Minimally invasive, video-assisted thyroidectomy (MIVAT) was first used in Pisa
      in 1998. The technique is characterized by a unique central access and external
      retraction. There is controversy about the validity and limited indications of
      this and other minimally invasive thyroidectomy techniques, but MIVAT looks
      promising. The results of MIVAT, in 5 years experience, are similar to those of
      traditional thyroidectomy.

PMID- 15145232
TI  - Extent of adrenalectomy for adrenal neoplasm: cortical sparing (subtotal) versus
      total adrenalectomy.
AB  - The standard operation on adrenal neoplasias is a complete adrenalectomy.
      Accepted exceptions are bilateral inherited pheochromocytomas. In these cases,
      clinical and biochemical cure, as well as preservation of cortical function, can
      be achieved by a noncomplete adrenalectomy. In that procedure, at least one third
      of one gland has to be preserved. In unilateral adrenal tumors, partial resection
      has been used, especially in Conns adenomas, with early results comparable to
      those of total adrenalectomy. Because longterm results are still limited in
      hyperaldosteronism, final conclusions are not possible today.

PMID- 15145233
TI  - Laparoscopic adrenalectomy for malignancy.
AB  - Laparoscopic adrenalectomy for primary malignancies and tumors metastatic to the
      adrenal is controversial. Most studies demonstrate that results of laparoscopic
      adrenalectomy for malignant lesions are similar to those of open adrenalectomy,
      without its morbidity. The results of laparoscopic adrenalectomy for tumor
      metastases suggest that it may benefit patients who have a metachronous
      metastasis from any of a variety of primary tumors. Selective laparoscopic
      adrenalectomy for potentially malignant tumors requires seeking signs of local
      invasion, lymphadenopathy, or distant metastasis; there are no other reliable
      preoperative criteria of malignancy. Diagnostic laparoscopy may be useful, and in
      some cases, may establish a diagnosis. Laparoscopic adrenalectomy should be
      cautiously performed, with the goals of achieving complete tumor resection
      without disruption of the adrenal capsule.

PMID- 15145234
TI  - Surgical treatment of insulinomas.
AB  - Differential diagnosis of hypoglycemic patients should include insulinoma. Plasma
      insulin-to-glucose ratio greater than 0.3 or C-peptide levels of 2 nmol/L or
      greater suggest insulinoma. Abdominal CT scan can exclude metastatic disease and
      identify uncommonly large islet cell tumors, but has poor sensitivity for
      localizing insulinomas; transgastric endoscopic ultrasound is the most sensitive
      technique. Palpation combined with intraoperative ultrasound identifies most
      tumors at operation and gives vital information about surrounding structures. If
      no tumor is found, blind distal pancreatectomy should not be performed, and the
      patient should be referred to an endocrinologist or endocrine surgeon for
      diagnostic confirmation and further localization. Laparoscopy is a viable
      alternative to open tumor resection; laparoscopic ultrasound can facilitate
      localization and guide safe resection.

PMID- 15145235
TI  - Asymptomatic primary hyperparathyroidism: a medical perspective.
AB  - The clinical phenotype of primary hyperparathyroidism in the United States has
      changed markedly over the past century, with the majority of patients having
      minimal overt symptomatology. It has become clear, however, that "asymptomatic"
      primary hyperparathyroidism is a disease with distinct physiologic
      characteristics. Data accumulated over recent years suggest that asymptomatic
      patients meeting specific criteria can be safely followed without surgery. These
      guidelines are elucidated, and new options in the medical therapeutics of primary
      hyperparathyroidism are discussed.

PMID- 15145236
TI  - Asymptomatic primary hyperparathyroidism: a surgical perspective.
AB  - Since the advent of multichannel autoanalyzers and routine screening of serum
      calcium levels, prevalence of primary hyperparathyroidism (pHPT) has increased to
      between 0.1% and 0.4%. As more patients present with "asymptomatic" pHPT, ideal
      treatment of "mild" disease becomes more controversial, with the possibility of
      safe, nonoperative management in a selected group of patients. Accumulated
      evidence confirms that the majority of these patients suffer from vague,
      nonspecific complaints that are very real and can improve following
      parathyroidectomy. Furthermore, parathyroidectomy in patients with pHPT has been
      demonstrated to improve bone mineral density, reduce fracture risk, and improve
      health-related quality of life and possibly overall survival. Therefore, all
      patients with primary hyperparathyroidism should be referred for surgical
      evaluation by an experienced endocrine surgeon.

PMID- 15145237
TI  - Extent of surgery for differentiated thyroid cancer.
AB  - The authors believe that total or near total thyroidectomy followed by 131I
      ablation and thyroid hormone suppression therapy are there commended extent of
      surgery and treatment of choice in differentiated thyroid cancer. This is based
      on retrospective data showing that total thyroidectomy plus 131I and thyroid
      stimulating hormone (TSH) suppression reduces disease recurrence and mortality,
      removes all intrathyroidal cancer, and facilitates the use of 131I scans and
      thyroglobulin measurements to monitor for recurrence. Recent decision analyses
      supporting this recommendation are summarized in this article. The recommendation
      comes with the caveat that total thyroidectomy must be performed safely with a
      low complication rate. With the institution of this appropriate treatment
      regimen, the prognosis for the majority of our patients with differentiated
      thyroid cancer is excellent.

PMID- 15145238
TI  - Hyperthyroidism: advantages and disadvantages of medical therapy.
AB  - The most common causes of hyperthyroidism are Graves' disease, toxic nodular
      goiter, and iodine-induced hyperthyroidism. Hyperthyroidism can be treated
      medically with antithyroid drugs or radioactive iodine, or surgically. Multiple
      clinical factors must be weighed when choosing a treatment modality. All of the
      available forms of therapy have advantages and disadvantages, and treatment
      choices must be individualized.

PMID- 15145239
TI  - Advantages and disadvantages of surgical therapy and optimal extent of
      thyroidectomy for the treatment of hyperthyroidism.
AB  - Surgery is excellent therapy for hyperthyroidism, with no mortality,and few
      complications or recurrences. It achieves euthyroidism rapidly and consistently,
      avoids long-term risks of radioactive iodine and antithyroid medications,
      provides tissue for histology,renders childbearing immediately possible, and
      allows absolute titration of thyroid hormone. Advancements such as preoperative
      preparation and intraoperative parathyroid hormone monitoring have decreased
      risks greatly and improved outcomes. Hartley-Dunhill procedure is the treatment
      of choice. Patients should be rendered euthyroid before operation to decrease
      thyroid vascularity, to improve surgical planes, and to prevent life threatening
      thyroid storm. Patients must be monitored carefully for hypocalcemia, a
      potentially serious complication. Patients will require lifelong thyroid hormone
      replacement. Radioactive iodine ablation should be considered for disease
      recurrence after surgery.

PMID- 15145240
TI  - Subclinical Cushing's syndrome in adrenal incidentalomas.
AB  - Up to 20% of patients with adrenal incidentalomas have abnormal cortisol
      production, and can be classified as having subclinical Cushing's syndrome.
      Although these tumors do not secrete enough cortisol to lead to the development
      of overt Cushing's syndrome, they are likely playing a contributory role in the
      development of hypertension, diabetes, osteoporosis, and obesity. Studies suggest
      that many of these problems can be reversed with surgical treatment.
      Additionally, if this diagnosis is not sought out before pursuing an
      adrenalectomy for an incidentaloma, the patient can develop profound
      postoperative adrenal insufficiency.

PMID- 15145241
TI  - Clinical manifestation of aldosteronoma.
AB  - Formerly, fewer than 1% of patients with hypertension were believed to have
      primary hyperaldosteronism; however, recent studies have suggested a higher
      prevalence, in 5% to 10% of patients with hypertension. Hypokalemia is not
      necessary for the diagnosis and is probably a sign of more advanced disease. The
      best diagnostic test is the plasma aldosterone concentration to plasma renin
      activity (PAC/PRA) ratio. Excess aldosterone level has a deleterious effect on
      the cardiovascular system. Aldosteronomas should be differentiated from
      idiopathic hyperaldosteronism (IHA),because they are curable by laparoscopic
      adrenalectomy.

PMID- 15145242
TI  - Management of thyroid incidentalomas.
AB  - The discovery of a thyroid incidentaloma warrants a systematic approach for those
      nodules most likely to be cancerous. An optimal management strategy for thyroid
      incidentalomas should be guided by four questions: (1) Does the incidentally
      detected thyroid nodule put the patient at risk for an adverse outcome; (2) Can
      those individuals with malignant thyroid nodules be identified; (3) Is the
      treatment of thyroid malignancy more effective in presymptomatic patients; and
      (4) Do the beneficial effects of presymptomatic detection and treatment in these
      patients justify the costs incurred Physicians caring for patients with thyroid
      disease should participate in data acquisition in national databases and properly
      randomized studies, to address the optimal management strategy in the treatment
      of incidentally-detected thyroid nodules.

PMID- 15145243
TI  - Redifferentiation therapy for thyroid cancer.
AB  - Thyroid tumorigenesis and carcinogenesis accompany progressive loss of thyroid
      specific differentiated functions. Some thyroid cancers are or become
      dedifferentiated, and they become refractory to efficacy-proven conventional
      therapies such as radioiodine ablation therapy and thyrotropin (TSH)-suppressive
      therapy. Redifferentiation therapy by either redifferentiating agents or gene
      transfer of differentiation-related genes may retard tumor growth and make tumors
      respond to conventional therapies.

PMID- 15145245
TI  - Open-air-nesting honey bees Apis dorsata and Apis laboriosa differ from the
      cavity-nesting Apis mellifera and Apis cerana in brood hygiene behaviour.
AB  - The cavity-nesting Apis mellifera and Apis cerana bees detect, uncap, and remove
      diseased brood. The hygiene behaviour of open-air-nesting bees Apis dorsata and
      Apis laboriosa was investigated in India and Nepal. Sealed A. dorsata pupae were
      pin-killed or deep-frozen. The workers removed 73 or 37% of damaged pin-killed
      pupae depending on the diameter of the pins, and only 7% of the frozen undamaged
      pupae. Migrating A. dorsata and A. laboriosa left unopened the sealed brood in
      deserted combs. Thus, A. dorsata and A. laboriosa do not open undamaged cells
      with dead brood. This behaviour is a more efficient mechanism in preventing the
      spread of diseases and parasitic mites than uncapping and removing dead pupae by
      A. mellifera and A. cerana. It may be beneficial for migrating A. dorsata and A.
      laboriosa to temporarily disuse part of the comb cells in exchange for arresting
      the mites there and thus reducing the increase of their population.

PMID- 15145247
TI  - Venom from the pupal endoparasitoid, Pimpla hypochondriaca, increases the
      susceptibility of larval Lacanobia oleracea to the entomopathogens Bacillus
      cereus and Beauveria bassiana.
AB  - Cellular immune responses in insects protect them against parasites and pathogens
      that enter their hemocoel. Venom from the solitary pupal endoparasitoid, Pimpla
      hypochondriaca, has previously been shown to suppress certain key, cell-mediated
      immune responses of Lacanobia oleracea. Experiments were performed to determine
      if L. oleracea larvae injected with P. hypochondriaca venom would be more
      susceptible to Bacillus cereus, or Beauveria bassiana, when these microorganisms
      were subsequently injected. Mortality due to B. cereus (approximately 15 colony
      forming units [CFU]/larva) and B. bassiana (approximately 2.4 x 10(3)
      conidia/larva) was enhanced by prior injection of 4 microg of venom. In addition,
      injection of venom/Dulbecco's phosphate-buffered saline (DPBS) or DPBS/B.
      bassiana reduced the rate at which larvae gained weight compared to control
      larvae. However, the greatest reduction in weight was recorded for larvae that
      had been injected with venom/B. bassiana conidia.

PMID- 15145246
TI  - Characterization of Mexican Bacillus thuringiensis strains toxic for lepidopteran
      and coleopteran larvae.
AB  - Bacillus thuringiensis strains C-4, C-9, GM-7, and GM-10, isolated from northeast
      Mexico and selected for their high toxicity against lepidopteran and coleopteran
      pests, were characterized following United States Environmental Protection Agency
      (EPA)'s guidelines. Flagellar serotyping revealed that GM-7 and GM-10 belonged to
      serotype aizawai, whereas C-4, C-9 corresponded to the kumamotoensis serotype. GM
      10 and C-9 were also shown to be the most effective against lepidoptera and
      coleoptera larvae, respectively. None of the tested strains produced beta
      exotoxin or showed activity against mosquitoes. GM-7 and GM-10 were sensitive to
      R-41 and CP-51 phages. All strains synthesized crystal proteins of 130-140 kDa.
      PCR analysis showed that C-4, GM-7, and GM-10 strains expressed cry1 genes, and C
      9 expressed cry3 and cry7/8 genes, but not cry1. However, the C-9 strain had no
      cross-reaction with antisera raised against Cry3A and Cry7A proteins. GM-7 and GM
      10 were sensitive to R-41 and CP-51 phages. When the delta-endotoxin (crystal)
      from the four strains was subcutaneously injected to Balb/c mice, alone or in
      combination with spores, only C-4 and C-9 provoked tissue necrosis similar to
      that caused by the beta-exotoxin producer HD-41. Tissue necrosis was prevented
      with the injection of pentoxifylline, an inhibitor of tumor necrosis factor alpha
      (TNF-alpha) production, suggesting a role of this cytokine in the observed
      effect. Our results demonstrated that GM-7 and GM-10 strains are effective and
      suitable for control of lepidopteran pests and safe for mammals under EPA
      regulations. The potential of the C-9 strain for the control of several
      coleopteran pests, and the induction of tissue necrosis in mice by C-4 and C-9
      strains, are discussed.

PMID- 15145248
TI  - Vegetative compatibility groups in indigenous and mass-released strains of the
      entomopathogenic fungus Beauveria bassiana: likelihood of recombination in the
      field.
AB  - Using nitrate non-utilizing (nit) mutants, we determined vegetative compatibility
      groups (VCG) among strains of Beauveria bassiana representing strains indigenous
      to North America, isolated from diverse insect hosts, and strains that have been
      mass released for insect control. Genetic similarity among these strains was
      analyzed using random amplified polymorphic DNA (RAPD) markers. Our data revealed
      23 VCGs among the 34 strains tested, with most of these groups comprised of only
      a single strain. We also observed a VCG comprised of eight genetically similar
      strains isolated from Colorado potato beetles (CPB). Co-inoculation studies of
      CPB larvae with complementary nit mutants from the same or from different VCGs
      revealed heterokaryosis in four out of five same-VCG pairs, with only 5-17% of
      the sporulating cadavers generating few parasexual recombinants. In contrast,
      none of the infected beetles treated with non-compatible pairs generated
      recombinants. The large number of VCGs observed and the low frequency of in vivo
      recombination limited to vegetatively compatible strains indicate that this
      self/non-self recognition system may be an effective barrier preventing genetic
      exchange between dissimilar strains in the field.

PMID- 15145249
TI  - Occurrence of Myrmicinosporidium durum in red imported fire ant, Solenopsis
      invicta, and other new host ants in eastern United States.
AB  - Myrmicinosporidium durum, a parasitic fungus in several ant species, is reported
      from seven new hosts collected in the eastern United States, including Solenopsis
      invicta, Solenopsis carolinensis, Paratrechina vividula, Pheidole tysoni,
      Pheidole bicarinata, Pyramica membranifera, and Pogonomyrmex badius. Spores can
      be found in most ant body parts, are dark brown when mature, and clear to light
      brown while immature. Ants infected with mature spores appear darker than normal.
      Spores from different hosts were 47-57 microm in diameter. Prevalence in host
      populations varied between 2 and 67% of the ants, and 3-100% of the colonies.
      Infection was most common in S. carolinensis with prevalence rates between 22 and
      67%. Prevalence rates for S. invicta individuals were lower than for other ants,
      however, prevalence rates within the infected colonies were as high as 31%.
      Observations of disease were recorded mostly from late summer and fall. Possible
      implications of this new disease in red imported fire ants are discussed.

PMID- 15145251
TI  - Low temperature cure of a male killing agent in Drosophila melanogaster.
AB  - Environmental factors can affect transmission or phenotype expression of selfish
      cytoplasmic endosymbionts such as embryonic male killers. Temperature is one
      factor that usually affects the transmission rate of selfish cytoplasmic
      endosymbionts. Heat cures have been described for several host-parasite systems,
      cold cures, however, are rare. We report a temperature cure of the Drosophila
      melanogaster male-killing agent, which occurs when flies are raised at 16.5
      degrees C. Flies grown at 20, 24, and 28 degrees C maintained an extremely female
      biased sexual proportion.

PMID- 15145250
TI  - Evaluation of an innate immune reaction to parasites in earthworms.
AB  - Encapsulation is an essential process of the invertebrate immune system and
      includes the prophenoloxidase (proPO) cascade. We present an assay for evaluating
      this immune response, now newly adapted to earthworms. Coelomic fluid is
      withdrawn and coelomocytes are stained with l-Dopa. We studied assay
      repeatability and the correlation between number of PO-active cells and infection
      level of the parasitic protozoan Monocystis sp. in the earthworm Lumbricus
      terrestris. Our study showed high assay repeatability although the expected
      negative relationship between PO-active coelomocytes and parasite load was not
      observed; yet a suggestion toward a positive relationship was detected. This
      finding is contrary to previous assumptions that presume coelomocyte
      concentrations to be the independent variable determining parasite load.

PMID- 15145252
TI  - Infection of the immature stages of Diadegma semiclausum, an endolarval
      parasitoid of the diamondback moth, by Beauveria bassiana.
AB  - Interactions between the immature stages of Diadegma semiclausum, an endolarval
      parasitoid of Plutella xylostella, and the fungal entomopathogen Beauveria
      bassiana were investigated in the laboratory. Detrimental effects of B. bassiana
      on D. semiclausum cocoon production and adult parasitoid emergence increased with
      increasing pathogen concentration and some parasitoid larvae became infected by
      B. bassiana within hosts. The negative impact of B. bassiana on D. semiclausum
      cocoon production decreased as temporal separation between parasitism and
      pathogen exposure increased. Adult parasitoid emergence was significantly
      compromised by the highest rates of B. bassiana tested even when exposure of host
      larvae to the pathogen was delayed until one day before predicted parasitoid
      cocoon formation. Parasitoid pupae were infected by the pathogen in all B.
      bassiana treatments which did not preclude their development.

PMID- 15145253
TI  - Paenibacillus larvae larvae spores in honey samples from Uruguay: a nationwide
      survey.
AB  - American foulbrood is a severe bacterial disease affecting larvae of the honeybee
      Apis mellifera and it is caused by Paenibacillus larvae larvae. The disease is
      present worldwide and cases have been reported in almost all the beekeeping
      regions of the five continents. During 2001 and 2002 we carried out a nationwide
      study to assess the presence and amount of P. l. larvae spores in honey samples
      from Uruguay, combining classic bacteriological, and molecular approaches. The
      distribution of P. l. larvae spores in honey of the whole country showed a clear
      pattern and may provide useful data for a control and prevention strategy of
      American foulbrood.

PMID- 15145254
TI  - Mass mortality of larval Eriocheir sinensis (Decapoda: Grapsidae) population bred
      under facility conditions: possible role of Zoothamnium sp. (Peritrichida:
      Vorticellidae) Epiphyte.

PMID- 15145255
TI  - Using bioassays to estimate abundance of Entomophaga maimaiga resting spores in
      soil.

PMID- 15145256
TI  - Vision for FIGO, 2003-2006.

PMID- 15145257
TI  - Mode of delivery for breech presentation in grandmultiparous women.
AB  - OBJECTIVES: To compare maternal and neonatal outcomes of planned vaginal delivery
      vs. elective cesarean delivery for breech presentation at term. METHODS:
      Retrospective study of term breech deliveries from January 1997 through December
      2000. A group of 128 women for whom vaginal delivery was planned was compared
      with a group of 122 women who had an elective cesarean delivery with regard to
      neonatal mortality and morbidity (birth trauma, birth asphyxia,
      hyperbilirubinemia, and duration of stay in the neonatal intensive care unit) and
      maternal morbidity (infections, hemorrhage, hysterectomy, deep venous thrombosis,
      and pulmonary embolism). RESULTS: There was no difference in neonatal mortality
      and morbidity between the two groups (13.0% vs. 9.4%). There were fewer maternal
      complications in the planned vaginal group than in the elective cesarean group
      (5.5% vs. 18%; P<0.01). In the planned vaginal delivery group 70% of multiparas
      and 85% of grandmultiparas were delivered vaginally compared with 50% of
      nulliparas. CONCLUSIONS: In breech presentations at term vaginal delivery can be
      achieved in 85% of grandmultiparas without significant neonatal morbidity.
      Elective cesarean section is associated with increased maternal morbidity
      compared with planned vaginal delivery.

PMID- 15145258
TI  - Hepatitis E in pregnancy.
AB  - OBJECTIVES: To study the spectrum and the clinical and biochemical course of
      viral hepatitis E during pregnancy. METHODS: In this prospective study, sera of
      62 pregnant women having jaundice in the third trimester of pregnancy were
      analyzed for markers of hepatitis A, B, C and E viruses. The cord blood samples
      of hepatitis E virus (HEV)-positive pregnant women at the time of delivery were
      tested for IgM anti-HEV antibodies by enzyme-linked immunosorbent assay and HEV
      RNA by reverse transcriptase polymerase chain reaction. RESULTS: Of the 62
      patients, 45.2% had HEV infection and nine developed fulminant hepatic failure
      (FHF). Eighty-one percent of FHF cases and 37.25% of acute viral hepatitis cases
      were caused by HEV. Approximately two-thirds of the pregnant women with HEV
      infection had preterm deliveries. The mortality rate among the HEV-positive
      pregnant women was 26.9%. Vertical transmission was observed in 33.3% of cases.
      CONCLUSIONS: One-third of the pregnant women with HEV infection had a severe form
      of hepatitis in the third trimester of pregnancy, i.e. FHF. Hepatitis E in
      pregnancy is associated with high rates of preterm labor and mortality.

PMID- 15145259
TI  - Maternal serum levels of dehydroepiandrosterone sulfate and labor induction in
      postterm pregnancies.
AB  - OBJECTIVES: To study the relationship between maternal endogenous
      dehydroepiandrosterone sulfate (DHEAS) levels, success of labor induction, and
      Bishop scores in postterm pregnancies. METHODS: There were 65 postterm
      pregnancies. Group 1 consisted of women spontaneously in the active phase of
      labor, and group 2 of women with hypotonic uterine contractions whose labor was
      inducted by oxytocin. Levels of DHEAS were studied from venous blood samples.
      Demographic data and Bishop scores were recorded. RESULTS: The demographic
      characteristics of patients were similar, but DHEAS levels were higher in group 1
      than in group 2 (P<0.001). Linear regression analysis showed a significant
      relationship between DHEAS and Bishop scores. DHEAS levels in women delivered
      vaginally were significantly higher than in women delivered by cesarean section.
      From the receiver operating characteristics (ROC) curve, DHEAS levels might
      determine the mode of delivery and success of labor induction; however, Bishop
      scores do not. CONCLUSIONS: DHEAS levels may be an important factor influencing
      the efficiency of labor and the success of labor induction in postterm
      pregnancies.

PMID- 15145260
TI  - Elective vs. conservative management of ovarian tumors in pregnancy.
AB  - OBJECTIVES: To determine optimal management of the ovarian tumors in pregnancy.
      METHODS: This study included 89 cases of the ovarian tumor in pregnancy that
      required surgery at Holy Family hospital of the Catholic University from January,
      1990 to December, 2001. Among 89 cases, 36 and 53 were emergency and elective
      surgery, respectively. Student's t-test and the chi(2)-test were used for
      statistical analysis and a P-value of <0.05 was considered statistically
      significant. RESULTS: The most common size of torsion of ovarian tumors during
      pregnancy was 6-10 cm and the incidence was the most frequent during the first
      trimester of pregnancy. The incidence of preterm delivery (<37 weeks) was higher
      in emergency surgery, but there was no difference in the gestational age at
      delivery, also no difference in the birth weight or the method of delivery.
      CONCLUSIONS: Although surgery for ovarian tumors in pregnancy is delayed until
      the onset of symptoms, adverse pregnancy outcome is not worsened when compared
      with that after elective surgery. We propose that conservative management would
      be used in optimal management of pregnant women with ovarian tumors.

PMID- 15145261
TI  - Risk of malignancy index in the preoperative evaluation of pelvic masses.
AB  - OBJECTIVES: To assess the ability of a risk malignancy index (RMI) based on serum
      levels of CA 125, ultrasound findings, and menopausal status to discriminate
      between benign and malignant pelvic masses in a particular population. METHODS: A
      retrospective study was conducted of 100 women with pelvic masses admitted for
      laparotomy. The sensitivity and specificity of serum levels of CA 125, ultrasound
      findings, and menopausal status were calculated both separately and combined into
      a RMI to diagnose malignancy. RESULTS: The RMI was more accurate than any single
      criterion in diagnosing malignancy. Using a cut-off level of 200 to indicate
      malignancy, the RMI gave a sensitivity of 90%, specificity of 89%, positive
      predictive value of 96%, and negative predictive value of 78%. CONCLUSION: The
      RMI is able to correctly discriminate between malignant and benign pelvic masses.
      It is a simple scoring system that can be introduced easily into clinical
      practice to facilitate the selection of patients who would benefit from primary
      surgery.

PMID- 15145262
TI  - Human papillomavirus infection and cervical ectopy.
AB  - OBJECTIVES: To investigate the prevalence of human papillomavirus (HPV), and HPV
      type 16 (HPV16) infection in cervical ectopy, and the presence of anti-HPV16
      secretory IgA (sIgA) antibodies. METHODS: DNA from patients with cervical ectopy
      (n=218), HPV-associated lesions (n=111), and controls without evidence of
      cervical ectopy or HPV infection (n=93) were analyzed by PCR for the presence of
      HPV and HPV16. The presence of mucosal sIgA antibodies against HPV16 capsid
      antigens (VLP) was assayed in cervical mucus by ELISA. RESULTS: Prevalence of HPV
      DNA was higher in cervical ectopy than in controls (P=0.04; OR=2.06; 95% CI 0.99
      4.33). HPV16 was 6.3 times more prevalent in cervical ectopy than in controls.
      Anti-HPV16 sIgA were detected more frequently in cervical ectopy patients than in
      controls (P=0.0004). CONCLUSIONS: Cervical ectopy correlates with HPV infection.
      HPV16 is highly prevalent in cervical ectopy. sIgA antibodies against HPV16
      capsids are generated in patients with cervical ectopy.

PMID- 15145263
TI  - Predictors of labor and vaginal birth after cesarean section.

PMID- 15145264
TI  - Vaginal fluid creatinine in premature rupture of membranes.

PMID- 15145265
TI  - Symphysiotomy in a Nigerian hospital.

PMID- 15145266
TI  - Fetal and maternal adrenal steroid levels and labor.

PMID- 15145267
TI  - Urine culture at removal of indwelling catheter after cesarean section.

PMID- 15145268
TI  - Medical abortion in combination with laminaria for first-trimester termination of
      pregnancy.

PMID- 15145269
TI  - Pregnancy in chronic myeloid leukemia patients treated with alpha interferon.

PMID- 15145270
TI  - Prophylactic cerclage for the prevention of preterm delivery.

PMID- 15145271
TI  - Intravaginal misoprostol vs. dinoprostone as cervical ripening and labor-inducing
      agents.

PMID- 15145272
TI  - Myopia and operative delivery in Croatia.

PMID- 15145274
TI  - Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and
      mastalgia.

PMID- 15145273
TI  - Comparison of two aromatase inhibitors in women with clomiphene-resistant
      polycystic ovary syndrome.

PMID- 15145275
TI  - Loss of heterozygosity (LOH) in ovarian cancer.

PMID- 15145276
TI  - N-acetyl-cysteine treatment for polycystic ovary syndrome.

PMID- 15145277
TI  - Efficacy of a novel pH-buffering tampon in preserving the acidic vaginal pH
      during menstruation.

PMID- 15145278
TI  - Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.
AB  - OBJECTIVES: Although some studies have reported that the arginine isoform on
      codon 72 of p53 increases the susceptibility to invasive cervical cancer, such
      data remain controversial. The objective of this study was to quantitatively
      summarize the evidence for such a relationship. METHODS: Our data sources
      consisted of a MEDLINE search of the literature published before December 2002,
      bibliography review, and expert consultation. Thirty-seven studies met the
      inclusion criteria. Information on sample size, study design, Hardy-Weinberg
      equilibrium, and method of genotype determination was abstracted by two reviewers
      using a standardized protocol. The overall odds ratio (OR) of the p53 gene on
      invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS:
      The overall OR (95% confidence interval) for cervical cancer among those with the
      homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with
      the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the
      overall OR among those with Arg/Arg was statistically significant in
      adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas
      (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR
      among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2
      2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased
      risk for invasive cervical cancer. However, the risk varied by country, cellular,
      and HPV type.

PMID- 15145279
TI  - Dimensions of informed consent to treatment.
AB  - Modern law approaches patients' consent to treatment not only through liability
      for unauthorized touching, namely criminal assault and/or civil (non-criminal)
      battery, but also through liability for negligence. Physicians must exercise
      appropriate skill in conducting procedures, and in providing patients with
      information material to the choices that patients have to make. The doctrine of
      informed consent serves the ethical goal of respecting patients' rights of self
      determination. Information is initially pitched at the reasonable, prudent person
      in the patient's circumstances, and then fine-tuned to what is actually known
      about the particular patient's needs for information. Elements to be disclosed
      include the patient's prognosis if untreated, alternative treatment goals and
      options, the success rate of each option, and its known effects and material
      risks. Risks include medical risks, but also risks to general well-being such as
      economic and similar reasonable interests. Consent is a continuing process, not
      an event or signed form.

PMID- 15145280
TI  - The occlusion technique: a procedure to assess the HMI of in-vehicle information
      and communication systems.

PMID- 15145281
TI  - Occlusion as a measure for visual workload: an overview of TNO occlusion research
      in car driving.
AB  - A process-oriented approach by systematically studying driver performance,
      distraction, and workload is the way to go for assessing safety effects of new
      telematics applications in vehicles. These systems may strive for drivers'
      attention and possibly lead to distraction from the primary task. Visual
      occlusion techniques appear to be an effective means of studying drivers' visual
      information processing performance. Studies to illustrate this include
      identifying the minimum visual information drivers need for driving (asking for
      visual information) and the evaluation of driver support systems such as heading
      control and adaptive cruise control with respect to visual workload. In other
      applications the occlusion technique is used to exclude 'visual array'
      information from the optic flow field. The temporary exclusion of part of the
      visual field of view was applied in evaluating the effects of different types of
      driver's side rearview mirrors.

PMID- 15145283
TI  - Task interruptability and duration as measures of visual distraction.
AB  - Tasks that are easily interrupted under intermittent viewing conditions may be
      less distracting while driving because they allow drivers greater control over
      task sharing decisions. This paper investigates the reliability and sensitivity
      of the occlusion paradigm as a potential means of measuring task interruptability
      and distraction. Twenty-four participants, between the ages of 21 and 34,
      completed two separate experimental sessions. In one session they performed three
      in-vehicle tasks (a radio-tuning task and two simulated visual search tasks)
      under occlusion and while unoccluded. In another session, participants completed
      the same in-vehicle tasks while driving in a simulator, without occlusion. The
      tasks did not differ in terms of total task time, yet significant differences
      were found using the occlusion paradigm and subjective workload ratings. Task
      interruptability and task duration both need to be considered when assessing the
      suitability of tasks for time-sharing with driving.

PMID- 15145282
TI  - Evaluation of in-vehicle HMI using occlusion techniques: experimental results and
      practical implications.
AB  - Despite the usefulness of new on-board information systems one has to be
      concerned about the potential distraction effects that they impose on the driver.
      Therefore, methods and procedures are necessary to assess the visual demand that
      is connected to the usage of an on-board system. The occlusion-method is
      considered a strong candidate as a procedure for evaluating display designs with
      regard to their visual demand. This paper reports results from two experimental
      studies conducted to further evaluate this method. In the first study,
      performance in using an in-car navigation system was measured under three
      conditions: static (parking lot), occlusion (shutter glasses), and driving. The
      results show that the occlusion-procedure can be used to simulate visual
      requirements of real traffic conditions. In a second study the occlusion method
      was compared to a global evaluation criterion based on the total task time. It
      can be demonstrated that the occlusion method can identify tasks which meet this
      criterion, but are yet irresolvable under driving conditions. It is concluded
      that the occlusion technique seems to be a reliable and valid method for
      evaluating visual and dialogue aspects of in-car information systems.

PMID- 15145284
TI  - On the highway measures of driver glance behavior with an example automobile
      navigation system.
AB  - An over-the-road study of visual-manual destination entry using an example
      original equipment GPS-based navigation system was accomplished in traffic on
      urban streets and motorways. The evaluation used typical drivers, and a vehicle
      instrumented to record driver eye glances and fixations, driver control inputs,
      and lateral lane position. The primary task was to drive in a safe manner, in
      traffic, while maintaining speed and lateral lane position. As a secondary task,
      the drivers entered successive destinations while driving, using a touch screen,
      and at their own pace. They were told there was no need to enter the destination
      quickly. Results are shown for driver glance behavior, lane keeping performance,
      and subjective ratings. Overall, the drivers were able to accomplish the
      destination entry tasks with acceptably short glance durations, acceptable total
      task times, and with satisfactory subjective ratings for ease of entry.

PMID- 15145285
TI  - Perspectives on occlusion and requirements for validation.
AB  - This paper discusses the limitations and potential of using an occlusion test to
      assess visual distraction and the suitability of an in-vehicle information system
      (IVIS) task for driving. This discussion was expanded from issues raised during a
      UK workshop on occlusion. The paper describes the research history and empirical
      foundations of occlusion. It describes some of the occlusion technology and
      applications for this procedure. Issues concerning the occlusion tasks and the
      duration and timing of occlusion are presented. The main part of this paper
      focuses on the priority research considerations for occlusion. The paper
      concludes with a description of some alternatives to occlusion and future
      research needs. It is concluded that the occlusion test has some promise, however
      the empirical basis for occlusion is lacking. If occlusion is to be developed as
      a metric to determine maximal safe visual distraction, substantial barriers
      remain.

PMID- 15145287
TI  - An ergonomic garment design for elderly Turkish men.
AB  - This paper presents an ergonomic garment design for elderly Turkish men. The
      purpose of this study was to determine elderly men's demands, needs and problems
      in regard to clothing and to design an ergonomic garment in the light of this
      knowledge. The sample consisted of 120 elderly men living in Ankara, the capital
      city of Turkey, and its province. A questionnaire was prepared and given to these
      people in order to determine their clothing demands and needs. It was established
      that most of our subjects need functional garments. An ergonomic garment has been
      designed using the obtained data. It was found that the design of clothing for
      the elderly requires attention to bodily changes from aging in order to
      facilitate and raise the quality of life. Specific suggestions are made to
      elderly people and to the ready-to-wear sector.

PMID- 15145286
TI  - Structural stability and reliability of the Swedish occupational fatigue
      inventory among Chinese VDT workers.
AB  - The aim of the present study was to test the structural stability and reliability
      of the Swedish occupational fatigue inventory (SOFI) for use in a group of
      Chinese visual display terminal (VDT) workers. A qualified translator was
      recruited to translate the Chinese version of the SOFI (SOFI-C). The content
      validity was established with 12 bilingual practitioners and seven professional
      experts. The translated SOFI was administered to 104 sedentary workers on two
      occasions with an interval of 60 min. Most of them were female (80.8%) and they
      had a mean age of 34.5 years. Fifty-one percent of them reported using a VDT for
      4h or more at work. Exploratory factor analysis revealed a five-factor solution,
      which was comparable to the original latent factors. Cronbach's alpha for the
      five-factor scales was between 0.88 and 0.95. The test-retest reliability was
      satisfactory with intra-class correlations ranging from 0.69 to 0.83. The workers
      who used a VDT for 4h or more had significantly higher SOFI scores than those who
      used one for less than 4 h (p = 0.007 - 0.046). The results indicated that the
      SOFI-C was valid and reliable for measuring fatigue among Chinese sedentary
      workers. The satisfactory structural stability suggested that cultural influences
      on the construct of fatigue were not strong. Its characteristics of
      discrimination of the sedentary workers who had high VDT exposure suggested that
      the SOFI-C would be a useful instrument for prevention and intervention programs
      designed for work-related injuries in the workplace.

PMID- 15145288
TI  - Influence of tyre inflation pressure on whole-body vibrations transmitted to the
      operator in a cut-to-length timber harvester.
AB  - The influence of tyre inflation pressure on whole-body vibrations transmitted to
      the operator during the movement of a cut-to-length timber harvester was
      evaluated. Vibration measurements were taken in three orthogonal (x, y, z) axes
      at tyre pressure settings of 138, 345 and 414 kPa. Vibration was predominant in
      the vertical (z) direction with the peak rms acceleration value for the operator
      seat (0.281 ms(-2)) occurring at approximately 3.2 Hz. The corresponding peak
      value for the operator cabin chassis was 0.425 m s(-2) at 4 Hz. At 414 kPa, there
      was potential health risk on the operator for exposures above 8h duration. The
      vibration total values recorded for the operator seat at the maximum tyre
      inflation pressure setting were classed as "fairly uncomfortable" (ISO standard
      2631-1), and vertical seat vibration transmissibility was highest between 4 and 8
      Hz at the 345 kPa tyre pressure setting. The recorded values of WBV were
      significantly reduced by a reduction in tyre inflation pressure which may
      therefore be used to moderate the magnitude of WBV on wheeled timber harvesters.

PMID- 15145289
TI  - Body-based interfaces.
AB  - This research explores different ways to use features of one's own body for
      interacting with computers. Such "body-based" interfaces may find good uses in
      wearable computing or virtual reality systems as part of a 3D multi-modal
      interface in the future, freeing the user from holding interaction devices. Four
      types of body-based interfaces have been identified: Body-inspired metaphor
      (BIM); Body-as-interaction-surface (BAIS); Mixed mode (MM); and Object mapping
      (OM). These four body-based interfaces were applied to a few different
      applications (and associated tasks) and were tested for their performance and
      preference. It was generally found that, among the four, the BIM exhibited low
      error rates, but produced relatively longer task completion times and significant
      fatigue. The BAIS method had the contrasting character of higher error rates, but
      shorter task completion times and lower intuitiveness. The OM method exhibited
      high error rates, longer completion times, and much fatigue. Overall, the MM was
      superior in terms of both performance and preference as it combined the merits of
      the above three methods. Thus, it is expected, for applications with many
      associated tasks, a careful division of tasks among those that have natural
      semantic links to body parts and those that do not, is necessary to design the
      most performing body-based interface.

PMID- 15145290
TI  - Automobile seat comfort prediction: statistical model vs. artificial neural
      network.
AB  - The current automobile seat comfort development process, which is executed in a
      trial and error fashion, is expensive and outdated. The prevailing thought is
      that process improvements are contingent upon the implementation of
      empirical/prediction models. In this context, seat-interface pressure measures,
      anthropometric characteristics, demographic information, and perceptions of seat
      appearance were related to an overall comfort index (which was a single score
      derived from a previously published 10-item survey with demonstrated levels of
      reliability and validity) using two distinct modeling approaches-stepwise, linear
      regression and artificial neural network. The purpose of this paper was to
      compare and contrast the resulting models. While both models could be used to
      adequately predict subjective perceptions of comfort, the neural network was
      deemed superior because it produced higher r2 values (0.832 vs. 0.713) and lower
      average error values (1.192 vs. 1.779).

PMID- 15145291
TI  - The effect of upper extremity support on upper extremity posture and muscle
      activity during keyboard use.
AB  - Forearm support during keyboard use has been reported to reduce neck and shoulder
      muscle activity and discomfort. However, the effect of forearm support on wrist
      posture has not been examined. The aim of this study was to examine the effect of
      3 different postures during keyboard use: forearm support, wrist support and
      "floating". The floating posture (no support) was used as the reference
      condition. A wrist rest was present in all test conditions. Thirteen participants
      completed 20 min wordprocessing tasks in each of the test conditions.
      Electromyography was used to monitor neck, shoulder and forearm muscle activity.
      Bilateral and overhead video cameras recorded left and right wrist extension,
      shoulder and elbow flexion and radial and ulnar deviation. The forearm support
      condition resulted in significantly less ulnar deviation (p < or = 0.007), less
      time spent in extreme ulnar deviation (p = 0.002) and less reports of discomfort
      than the "floating" condition (p = 0.002). The wrist support but not the forearm
      support condition resulted in less trapezius and anterior deltoid muscular
      activity (p < 0.007). These findings indicate that typing with upper extremity
      support in conjunction with a wrist rest may be preferable to the "floating"
      posture implicit in current guidelines.

PMID- 15145292
TI  - Evaluation in industry of a draft code of practice for manual handling.
AB  - This paper reports findings from a study which evaluated the draft New Zealand
      Code of Practice for Manual Handling. The evaluation assessed the ease of use,
      applicability and validity of the Code and in particular the associated manual
      handling hazard assessment tools, within New Zealand industry. The Code was
      studied in a sample of eight companies from four sectors of industry. Subjective
      feedback and objective findings indicated that the Code was useful, applicable
      and informative. The manual handling hazard assessment tools incorporated in the
      Code could be adequately applied by most users, with risk assessment outcomes
      largely consistent with the findings of researchers using more specific
      ergonomics methodologies. However, some changes were recommended to the risk
      assessment tools to improve usability and validity. The evaluation concluded that
      both the Code and the tools within it would benefit from simplification, improved
      typography and layout, and industry-specific information on manual handling
      hazards.

PMID- 15145293
TI  - An assessment system for rating scientific journals in the field of ergonomics
      and human factors.
AB  - A method for selecting and rating scientific and professional journals
      representing the discipline of ergonomics and human factors is proposed. The
      method is based upon the journal list, impact factors and citations provided by
      the Institute of Scientific Information (ISI), and the journal list published in
      the Ergonomics Abstracts. Three groups of journals were distinguished. The
      'ergonomics journals' focus exclusively on ergonomics and human factors. The
      'related journals' focus on other disciplines than ergonomics and human factors,
      but regularly publish ergonomics/human factors papers. The 'basic journals' focus
      on other technical, medical or social sciences than ergonomics, but are important
      for the development of ergonomics/human factors. Journal quality was rated using
      a maximum of four categories: top quality (A-level), high quality (B-level), good
      quality (C-level)) and professional (P-level). The above methods were applied to
      develop the Ergonomics Journal List 2004. A total of 25 'ergonomics journals', 58
      'related journals' and 142 'basic journals' were classified.

PMID- 15145294
TI  - From the Epilepsy Foundation.

PMID- 15145295
TI  - Magnetoencephalography: an investigational tool or a routine clinical technique?
AB  - Magnetoencephalography (MEG) is a relatively novel noninvasive technique, with a
      much shorter history than EEG, that conveys neurophysiological information
      complementary to that provided by EEG, with high temporal and spatial resolution.
      Despite its a priori, highly competitive profile, the role of MEG in the clinical
      setting is still controversial. We briefly review the major obstacles MEG faces
      in becoming a routine clinical test and the different strategies needed to bypass
      them. The high cost and complexity associated with MEG equipment are powerful
      hindrances to wide acceptance of this relatively new technique in clinical
      practice. The most straightforward advantage is based on the relative facility of
      MEG recordings in the process of source localization, which also carries some
      degree of uncertainty, thus partly explaining why the development of clinical
      applications of MEG has been so slow. Obviously, a decrease in the cost and the
      elaboration of semiautomatic protocols that could reduce the complexity of the
      studies and favor the development of consensual strategies, as well as a major
      effort on the part of clinicians to identify clinical issues where MEG could be
      decisive, would be most welcome.

PMID- 15145296
TI  - Autonomic seizures and autonomic status epilepticus peculiar to childhood:
      diagnosis and management.
AB  - Autonomic seizures and autonomic status epilepticus in children have a high
      prevalence, manifest with dramatic clinical symptoms, and have important clinical
      and management implications. They probably affect approximately 13% of children
      aged 3-6 years with one or more nonfebrile seizures, or 6% in the age group 1-15.
      The primary cause is an idiopathic age-dependent epileptogenic susceptibility
      (Panayiotopoulos syndrome), but 10-20% are due to cerebral pathology. Autonomic
      seizures and autonomic status epilepticus have been best studied in
      Panayiotopoulos syndrome, which has been confirmed worldwide in more than 800
      cases and recently recognized in the new classification scheme of the
      International League Against Epilepsy. Seizures start with autonomic symptoms,
      mainly emesis, while the child is usually fully conscious. Other more
      conventional seizure manifestations often ensue, but autonomic manifestations
      commonly predominate to the end of the seizure. Ictal syncope (transient loss of
      consciousness and postural tone) is an intriguing common symptom. Half of the
      seizures last longer than 30 minutes, constituting autonomic status epilepticus.
      Prognosis is invariably excellent except for the symptomatic cases. The
      interictal EEG shows great variability from normal to severely epileptogenic,
      often with multifocal spikes. Pathophysiology of Panayiotopoulos syndrome is
      unknown, but it is likely that they are due to diffuse maturation-related
      epileptogenicity activating susceptible-for-children emetic centers and the
      hypothalamus. Thus, Panayiotopoulos syndrome is not occipital epilepsy, with
      which it is often erroneously equated. Autonomic seizures and autonomic status
      epilepticus are frequently misdiagnosed and often treated as encephalitis,
      atypical migraine, cardiogenic syncope, or other unrelated medical conditions
      such as gastroenteritis. This review examines the existing evidence, provides a
      means of improving diagnostic yield, and proposes practice parameters and
      guidelines for the diagnosis and management of autonomic seizures and autonomic
      status epilepticus in children.

PMID- 15145298
TI  - Extended-release formulations: simplifying strategies in the management of
      antiepileptic drug therapy.
AB  - Advances in our understanding, diagnosis, and treatment of seizure disorders have
      transformed the management of epilepsy. As the number of antiepileptic drugs and
      their formulations increase, so do the expectations of therapy. Once limited to
      attaining complete control of seizures, epilepsy management now strives to enable
      patients to lead lifestyles consistent with their own capabilities. Extended
      release antiepileptic drug formulations can help achieve the primary treatment
      goals for many patients with epilepsy: preventing occurrence of seizures and
      preventing or reducing side effects. The dosing flexibility and consistency of
      serum levels (without marked peak-to-trough fluctuations) conferred by extended
      release formulations help achieve these goals. These same attributes of extended
      release formulations may also improve compliance, quality of life, and patient
      satisfaction with treatment.

PMID- 15145297
TI  - Antiepileptic drugs and reduced bone mineral density.
AB  - There is a growing interest in recognizing the association between antiepileptic
      drugs and reduced bone mineral density. Although the literature regarding this
      association has been available for more than three decades, the management of
      this complication remains unclear. We review the relevant literature regarding
      antiepileptic drugs and reduction in bone mineral density with the aim of
      developing some guidelines for practical management of this problem. This review
      focuses on the mechanism of antiepileptic drug-induced bone loss, its
      recognition, and its management.

PMID- 15145299
TI  - Teachers' attitudes toward students with epilepsy: results of a survey of
      elementary and middle school teachers.
AB  - This article describes an effort to increase and expand the limited current
      understanding of teachers' attitudes toward epilepsy. A survey was conducted
      among 135 elementary and middle school teachers in the state of Kentucky
      regarding their attitudes toward persons with epilepsy. The survey included an
      indirect, error-choice attitude measurement scale, the Test of Knowledge about
      Epilepsy (KAE). In addition, information about demographic and professional
      preparation was obtained from the participants for the purpose of examining
      whether these variables predicted attitude scores. The teachers' scores on the
      KAE ranged from -12 to +18. The mean score was 2.87 (SD=6.50). More years of
      teaching experience and experience teaching a student with epilepsy predicted KAE
      scores. The results are discussed in terms of their implications for the need for
      further research and the development of effective teacher education
      interventions.

PMID- 15145300
TI  - Add-on melatonin improves quality of life in epileptic children on valproate
      monotherapy: a randomized, double-blind, placebo-controlled trial.
AB  - This randomized, double-blind, placebo-controlled study in epileptic children
      aged 3-12 years evaluated the effects of add-on melatonin administration on the
      quality of life of these children on sodium valproate (VPA) monotherapy using a
      parental questionnaire. Quality of Life in Childhood Epilepsy is a questionnaire
      designed to assess a variety of age-relevant domains such as physical function,
      emotional well-being, cognitive function, social function, behavior, and general
      health. Of the 31 patients, 16 randomly received add-on melatonin (MEL), whereas
      15 received add-on placebo (P). The questionnaire had good internal consistency
      reliability, because for most of the multi-item scales Cronbach's alpha
      reliability exceeded 0.5 (range: 0.59-0.94). To our knowledge, this is the first
      study assessing quality of life in epileptic children with add-on melatonin
      administration in the form of a randomized, double-blind, placebo-controlled
      trial. The study suggests a potential use of melatonin as an adjunct to
      antiepileptic therapy due to its diverse spectrum of action as an antioxidant,
      neuroprotector, and free radical scavenger, thus offering the advantage of
      reducing oxidant stress and subsequent damage. The beneficial effects of
      melatonin on sleep, its wide safety window, and its ability to cross the blood
      brain barrier have the potential to improve quality of life in pediatric
      epilepsy.

PMID- 15145301
TI  - Evidence of the antiepileptic potential of amiloride with neuropharmacological
      benefits in rodent models of epilepsy and behavior.
AB  - Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating
      neuronal pH and, hence, modulate bioelectric and seizure activity. In this study,
      we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on
      increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced
      seizures in mice. Further, the effect of amiloride on mood, memory, grip
      strength, and rotarod performance was also evaluated. The forced swimming test
      (FST) and spontaneous alternation behavior (SAB) models were employed to assess
      the effects on mood and memory, respectively. Amiloride produced a dose-dependent
      increase in seizure threshold in both rodent models of epilepsy. It was observed
      that amiloride reduced behavioral depression in the FST in mice. In addition, it
      resulted in memory improvement in the SAB model. Amiloride did not affect grip
      strength and rotarod performance, suggesting it is devoid of behavioral
      impairment. The results indicate the potential antiseizure activity of amiloride
      along with additional neurological advantages.

PMID- 15145303
TI  - The impact of comorbid depression on health resource utilization in a community
      sample of people with epilepsy.
AB  - This study assessed the impact of comorbid depression on health care utilization
      and health care coverage by people with epilepsy in US communities using a postal
      survey questionnaire. People with untreated depression used significantly more
      health resources of all types assessed with and without adjustment for seizure
      type, seizure recency, and days with epilepsy symptoms. The number of visits to
      medical doctors and psychiatrists differed significantly among people with no (N
      = 443), mild to moderate (N = 58), and severe (N = 148) symptoms of depression
      who were not receiving antidepressant treatment (all P < 0.001). People with
      current symptoms treated with antidepressants had more medical visits than people
      with no current symptoms ( P=0.016 ). People with current symptoms but not
      treated for depression had more medical and psychiatric visits than people with
      no current symptoms (both P = 0.001). These data highlight the impact of comorbid
      depression on health care utilization by people with epilepsy.

PMID- 15145302
TI  - Cognitive function in juvenile myoclonic epilepsy.
AB  - In this study, we examined 35 patients with juvenile myoclonic epilepsy (JME) and
      35 healthy volunteers. We used tests of cognitive performance (mini mental state
      examination, verbal and visual memory, visuospatial, frontal function,
      attention). In the JME group, we examined age, sex, family history, education
      level, age of seizure onset, seizure types, characteristics of EEG, duration of
      the therapy, drug dose and level, and verbal IQ level. Additionally, patients
      initially diagnosed as JME and patients who were initially under inappropriate
      drug therapy because of misdiagnosis were compared. As a result, we found
      statistically significant differences between JME patients and the control group
      with respect to verbal and visual memory. Furthermore, JME patients had impaired
      frontal and visuospatial function compared with the control group. We detected
      negative effects of younger age, family history, and absence seizures on
      cognitive function in JME patients.

PMID- 15145304
TI  - Improvement in seizure control and quality of life in medically refractory
      epilepsy patients converted from polypharmacy to monotherapy.
AB  - In a retrospective chart review, we identified 35 patients with medically
      refractory epilepsy (MRE) who had been converted from polypharmacy to monotherapy
      and maintained on monotherapy for at least 12 months. None of the 35 patients had
      worsening of their seizure frequency after the conversion to monotherapy.
      Fourteen of the 35 patients (40%) became seizure-free. Nine of 35 patients (26%)
      had a 50% reduction in seizure frequency. Five of 35 patients (14%) had a 75%
      reduction in seizure frequency. Twenty-eight (80%) of 35 patients participated in
      a quality-of-life questionnaire. Quality of life was rated as better on
      monotherapy as compared with polypharmacy in a number of domains: memory loss,
      concern over medication long-term effects, difficulty in taking the medications,
      trouble with leisure time activities, and overall state of health. This
      improvement reached statistical significance. Conversion to monotherapy in
      patients with MRE may be successful in achieving a reduction in seizure frequency
      and an improvement in quality-of-life parameters. A prospective, randomized trial
      is necessary to validate these findings.

PMID- 15145305
TI  - Linguistic deficits following left selective amygdalohippocampectomy: a
      prospective study.
AB  - Language deficits in 10 patients with medically intractable left-sided temporal
      lobe epilepsy prior to and following selective amygdalohippocampectomy are
      described. Preoperatively, a pattern of minor linguistic deficits was observed in
      three patients; isolated minor naming deficits were detectable in one additional
      patient. Three months after surgery, six patients' linguistic functions were
      unchanged, whereas in four patients, a significant decline in linguistic
      functions could be observed. All four patients revealed a very similar language
      syndrome characterized by reduced language comprehension and fluency, well
      articulated speech, frequent word-finding difficulties, circumlocutions, and
      semantic paraphasias in the absence of any phonological disorder. These deficits
      remained stable during the 12-month follow-up period. However, magnetic resonance
      imaging did not show any neocortical lesions outside the resection area. Possible
      explanations for these findings include neuronal cell loss and deafferentiation
      in cortical areas, disruption of the basal temporal language area pathways,
      reorganization of the language network in chronic temporal lobe epilepsy, and
      neocortical lesions due to the surgical intervention. Furthermore, correlations
      between linguistic and demographic data for our patients suggest that patients
      older at epilepsy onset are at greater risk for developing postoperative language
      deficits.

PMID- 15145306
TI  - Prevalence of epilepsy and health status of adults with epilepsy in Georgia and
      Tennessee: Behavioral Risk Factor Surveillance System, 2002.
AB  - Behavioral risk factors associated with comorbidity in people with epilepsy are
      largely unknown. We studied a population-based sample of 8057 adults through the
      2002 Behavioral Risk Factor Surveillance System, in Georgia and Tennessee,
      ascertaining a lifetime epilepsy prevalence of 2.1% in this population. This
      structured interview revealed that those with epilepsy had significantly worse
      self-reported fair or poor health status (39% vs 17% in adults without epilepsy),
      significantly greater cigarette smoking (38.8% vs 24.9% in other adults), and
      high rates of obesity (34.1% vs 23.7% in adults without epilepsy). Large
      percentages of adults with epilepsy reported currently symptomatic asthma and
      recent joint pain. Adults with epilepsy had lower educational attainment and
      lower household incomes, but a higher rate of medical insurance coverage, than
      did other adults. This type of population-based survey can serve to identify
      health disparities, behavioral risk factors for other chronic diseases, and unmet
      health care needs in individuals with epilepsy, and to track changes in these
      measures over time.

PMID- 15145307
TI  - Patient-validated content of a Greek version of the Quality of Life in Epilepsy
      Inventory (QOLIE-89) combined with individualized measures.
AB  - PURPOSE: The goal of this study was to determine the content validity of a Greek
      version of the Quality of Life in Epilepsy Inventory (QOLIE-89) and to
      investigate whether it can be developed in combination with individualized
      measures to assess the health-related needs of the individual patient with
      epilepsy in Cyprus. METHODS: The QOLIE-89 was translated into Greek and combined
      with individualized validation measures. The instrument was administered to 44
      adult outpatients receiving medication for epilepsy. They were asked to evaluate
      the clarity and appropriateness of the QOLIE-89 content and the accuracy of their
      scores, and to report their quality-of-life-related concerns. Reported concerns
      were compared with the QOLIE-89 scores and content. RESULTS: The majority of
      participants (92.9%) endorsed the representativeness of the assessment. Quality
      of-life (QoL) overall scores correlated significantly with satisfaction with QoL.
      Twenty-seven (30.3%) QOLIE-89 items were deemed unclear or difficult to answer
      and 13 items (14.6%) were deemed not relevant or inappropriate by > or =7.1% (N =
      3) of patients. At least 7.1% of participants disagreed that their scores were
      representative of their self-perceived QoL, on 23 items (25.8%). Participants
      reported 33 QoL-related concerns, of which nearly a quarter were not addressed in
      the original QOLIE-89. Correlations of QOLIE-89 domains with content-related
      concerns ranged from phi = 0.43 to phi = 0.85 ( P < 0.01), lower correlations
      coinciding with the scale content that was criticized. CONCLUSIONS: Patients were
      able to use superimposed measures to evaluate the content of QOLIE-89 and
      identified areas that could be incorporated into an instrument for the
      determination of patients' individual QoL-related concerns.

PMID- 15145308
TI  - Topiramate in clinical practice: long-term experience in patients with refractory
      epilepsy referred to a tertiary epilepsy center.
AB  - For the treatment of patients with chronic refractory epilepsies, information
      about the long-term efficacy and safety profile of any new antiepileptic drug is
      crucial. Topiramate has been proven to be effective in patients with refractory
      chronic partial epilepsies in short-term controlled clinical trials, but the long
      term retention, long-term efficacy, and long-term side-effect profile have not
      been sufficiently investigated. We analyzed all patients who had been treated
      with topiramate in the Epilepsy Centre Kempenhaeghe from the introduction of the
      drug in the spring of 1993 up to a final assessment point in mid-2002. In total,
      470 patients were identified. The data show that the clinical dose achieved was
      about 200mg/day, reached after approximately 6 months of treatment. Further dose
      escalation in the survivors was slow, with a mean dose of about 300 mg/day after
      24 months of treatment. Mean titration dose is 25mg/week, but titration strategy
      is mostly individual and responds to patient complaints. With respect to seizure
      frequency, 10-15% of the patients were seizure-free at the 6-month evaluation; 4
      patients achieved a 2-year remission. Retention rate was 53% after 1 year, 45%
      after 2 years, 38% after 3 years, and 30% after 4 years. At 4 years, almost 70%
      of the patients had discontinued topiramate. The main reason was adverse events,
      which accounted for about 65% of the discontinuations. Behavioral side effects
      were dominant, with mental slowing (27.6%), dysphasia (16.0%), and mood problems
      (agitation: 11.9%) being the most frequently reported side effects. In about 10%
      of the patients side effects led to discontinuation despite the obvious favorable
      effects on seizure frequency. Comparisons between the patients who discontinued
      topiramate treatment and those who continued topiramate showed that
      discontinuation was associated with comedication (vigabatrin and lamotrigine).
      Our conclusion is that TPM is associated with a high incidence of side effects in
      clinical practice, affecting long-term retention. Meaningful prognostic factors
      that may help us in clinical decision making, i.e., to prevent the side effects
      or to help us identify those at risk, have not been found.

PMID- 15145309
TI  - The effects of pentylenetetrazole-induced status epilepticus on behavior,
      emotional memory, and learning in rats.
AB  - Status epilepticus (SE) can cause spatial learning, memory, and behavioral
      deficits; however, little information is available, especially regarding the
      effects of such seizures on emotional memory and learning functions. We
      investigated the effects of SE on emotional memory, learning, and behavior in
      mature rats over short and long periods. SE was induced in 50- to 60-day-old rats
      (P50-P60) using intraperitoneal injections of pentylenetetrazole (PTZ, n = 20);
      control rats received saline (n = 10). All animals were tested with elevated T
      maze and open-field tests on the 1st, 7th, 14th, and 180th days after SE to
      evaluate emotional memory, learning, and behavior. The number of fecal boli
      increased, and one-way escape latency was long in a short period after SE. PTZ
      induced SE causes transient memory deficits, which is related to unconditioned
      fear, but it did not cause any persistent abnormalities of behavior, emotional
      memory, and learning in mature rats.

PMID- 15145311
TI  - Medication management by the person with epilepsy: perception versus reality.
AB  - PURPOSE: In an attempt to understand if perception of medication management
      matched actual medication management, we examined epilepsy patients' perceptions
      of their overall medication management and their actual management. METHODS: The
      investigators interviewed 25 adults with refractory epilepsy regarding
      perceptions of their past overall medication management. Following the interview,
      each subject received the Medication Event Monitoring System (MEMS) and was asked
      to use it for 1 month. For the 21 persons who used and returned the caps, a score
      for compliance was calculated by dividing the number of compliant days by the
      total number of days. RESULTS: Four participants stated that they may sometimes
      forget to take their medications, and three patients said that they self
      regulated their medications to fit their lifestyle. The self-regulation was not
      reflected in the MEMS cap data. Fourteen participants reported that it was not
      difficult to manage their medication regimen. MEMS cap data showed that 11
      participants had a compliance score greater than 80% and 10 had a compliance
      score lower than 34%, but patients' perceptions of their past overall compliance
      did not differ between these groups. CONCLUSION: Although 14 of the participants
      reported that managing their medications was not a problem, MEMS cap data
      suggested that 10 of the participants did have difficulties managing their
      medication.

PMID- 15145310
TI  - Persistent severe amnesia due to seizure recurrence after unilateral temporal
      lobectomy.
AB  - Anterograde amnesia is a severely disabling state which has been reported as a
      consequence of bilateral mesiotemporal lesions in humans. In the present paper,
      recurrent epileptic seizures after temporal lobectomy are described as a rare
      cause of severe amnesia in two patients. Diffusion-weighted MRI in one patient
      showed cytotoxic edema during a nonconvulsive status epilepticus and subsequent
      progressive hippocampal atrophy within the following month. In the other patient,
      repeated conventional MRI revealed no structural abnormalities in the
      contralateral temporal lobe.

PMID- 15145312
TI  - Multimodal functional mapping of sensorimotor cortex prior to resection of an
      epileptogenic perirolandic lesion.
AB  - The effects of chronic epileptogenic lesions on functional anatomy are under
      debate. Our recent experience during mapping and resection of a lesion in
      sensorimotor cortex supports the idea that epileptogenic lesions may prompt
      development of alternate cortical motor representations. Multimodal mapping may
      uncover alternate areas of functionality that make surgery feasible even when
      conventional neuroanatomy suggests otherwise. Newer methods such as
      electrocorticographic spectral analysis may complement traditional electrical
      cortical stimulation mapping.

PMID- 15145313
TI  - Diffusion-weighted imaging and status epilepticus during vagus nerve stimulation.
AB  - PURPOSE: Transient abnormalities have been reported on diffusion-weighted imaging
      (DWI) during status epilepticus. Vagus nerve stimulation (VNS) is a therapy for
      epilepsy that has previously demonstrated alteration in regional cerebral blood
      flow on functional neuroimaging. We describe the peri-ictal DWI abnormalities in
      a patient with status epilepticus. METHODS: A 21-year-old woman with
      pharmacoresistant localization-related epilepsy was treated with VNS and
      underwent brain magnetic resonance imaging (MRI) with DWI for clinical purposes.
      RESULTS: Transient and reversible hyperintense signal abnormalities were noted on
      DWI at the site of seizure onset, in addition to the thalamus and midbrain
      bilaterally. A concomitant decrease in the apparent diffusion coefficient
      mimicked ischemia, yet complete clinical, and electrographic resolution occurred
      following successful termination of status. CONCLUSIONS: High-energy brain MRI
      sequences using DWI were safely performed in our epilepsy patient with a vagus
      nerve stimulator who experienced status epilepticus. This case highlights the
      bilateral and robust involvement of subcortical structures present immediately
      following status epilepticus. Additionally, bilateral abnormalities in the
      thalamus and midbrain in addition to the region of seizure origin, were observed
      in our patient implanted with a vagus nerve stimulator. Modulation of regional
      cerebral blood flow is one potential mechanism of action for VNS in humans;
      therefore, these regions of involvement could reflect the effects of status
      epilepticus, activation or facilitation by VNS, or both.

PMID- 15145314
TI  - Unilateral spatial neglect following right inferior parietal cortectomy.
AB  - Research in brain-damaged patients has suggested that the right hemisphere plays
      a role in unilateral spatial neglect (USN), but provides only limited information
      for pinpointing the intraparietal localization of the lesions associated with
      this syndrome. We report a case of unilateral neglect in a patient who underwent
      a right inferior parietal cortectomy for refractory epilepsy without any
      macroscopic lesion. We describe the evolution of the neuropsychological
      disturbances observed at 3 and 24 months after cortectomy. This case illustrates
      the role played by the inferior parietal lobe and, particularly, the parietal
      opercule in USN syndrome, and provides strong "experimental" evidence of the
      special role played by the inferior parietal lobule in the perception processes
      related to spatial attention.

PMID- 15145315
TI  - Unruptured aneurysm of the middle cerebral artery presenting with psychomotor
      seizures: case study and review of the literature.
AB  - An intracranial aneurysm would be low on the differential diagnosis of a patient
      presenting with behavioral or emotional changes. Nonetheless, complex partial
      seizures (CPS) may cause such symptoms and result from an unruptured intracranial
      aneurysm. Failure to diagnose and treat this condition in a timely manner
      increases the patient's risk of catastrophic aneurysmal rupture. This report
      describes a 55-year-old woman who presented following two CPS which began with
      the perception of a strange smell and culminated in a brief loss of
      consciousness. She had no history of seizure disorder or recent trauma. Magnetic
      resonance imaging (MRI) revealed a space-occupying lesion over the right temporal
      lobe near the amygdala. Magnetic resonance angiography (MRA) confirmed a 1.5-cm
      right middle cerebral artery aneurysm, with a dome projecting toward the
      amygdalohippocampal region. Following surgical ablation, the patient's CPS were
      well controlled. A review of the literature is performed on this unusual etiology
      and management strategies are discussed.

PMID- 15145316
TI  - Receptor revision in T cells: an open question?
AB  - During lymphocyte development, both B and T cells assemble antigen receptor
      variable region genes from germline gene segments, allowing the expression of
      unique receptors in each clonally derived lymphocyte. Previously, it was shown
      that in certain cases, progenitor and immature B cells are capable of editing
      their receptors to a new specificity on encounter with self-antigens. Although
      the existence of such a process in T cells remains controversial, recent studies
      suggest that mature T cells are able to similarly revise their receptors in the
      periphery.

PMID- 15145317
TI  - The two NF-kappaB activation pathways and their role in innate and adaptive
      immunity.

PMID- 15145318
TI  - Coagulation in arthropods: defence, wound closure and healing.

PMID- 15145319
TI  - Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and
      "Type 1" inflammatory gene expression.

PMID- 15145320
TI  - Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and
      plasticity.

PMID- 15145321
TI  - Leukotrienes and atherosclerosis: new roles for old mediators.
AB  - Lipid mediators generated from arachidonic acid through the action of 5
      lipoxygenase have been known for over two decades and are implicated in a wide
      variety of inflammatory disorders. G-protein-coupled receptors mediate the
      effects of different leukotrienes in distinct cell types. Novel cellular and
      molecular targets were recently discovered for these mediators, with important
      consequences for the function of both adaptive and innate immune systems. These
      studies have outlined crucial new roles for leukotrienes in the recruitment of T
      lymphocytes and in the development of atherosclerotic lesions, suggesting novel
      mechanisms for their actions. Through the development of appropriate animal
      models, leukotrienes are becoming renewed targets for treatment of many
      inflammatory diseases including atherosclerosis.

PMID- 15145323
TI  - NK cells: innate immunity against hematological malignancies?
AB  - Recent advances in the treatment of malignant haemopathies enable increased
      remission and cure rates, however, many patients relapse and finally die.
      Although specific immunity mediated by cytolytic T-lymphocytes might have an anti
      cancer role, tumours escape from T-cell-based immune surveillance using various
      mechanisms, such as downregulation, mutation or loss of HLA class I molecules. As
      a consequence, these transformed cells could become targets for natural killer
      (NK) cells, whose cytotoxic capabilities are not blocked by HLA class I molecule
      engagement by specific inhibitory receptors. Novel developments in NK-cell
      research, particularly the identification of the role of non-HLA-restricted
      activating receptors (and in some cases of their ligands), have recently enabled
      us to reconsider NK-cell interactions with haematological malignant cells.

PMID- 15145322
TI  - What is the importance of the immunological synapse?
AB  - The immunological synapse (IS) has proved to be a stimulating concept,
      particularly in provoking discussion on the similarity of intercellular
      communication controlling disparate biological processes. Recent studies have
      clarified some of the underlying molecular mechanisms and functions of the IS.
      For both T cells and natural killer (NK) cells, assembly of the IS can be
      described in stages with distinct cytoskeletal requirements. Functions of the IS
      vary with circumstance and include directing secretion and integrating positive
      and negative signals to determine the extent of response.

PMID- 15145324
TI  - Diabetes mellitus and psychological well-being. Change between 1984-1986 and 1995
      1997. Results of the Nord-Trondelag Health Study.
AB  - Previous research has documented that people with diabetes report lower
      psychological well-being than do people with no reported disease. In recent
      years, new treatment regimens for diabetes have been introduced, including
      improved insulin and tablet treatment, easier blood sugar tests, and transfer of
      responsibility from doctor to patient. Have these improved methods for
      controlling diabetes resulted in enhanced psychological well-being for this group
      of patients? In this paper, we analyze changes in psychological well-being
      between 1984-1986 and 1995-1997 among diabetic patients. On these two occasions,
      the entire adult population of one county in Norway was invited to a health
      screening (the Nord-Trondelag Health Studies, HUNT 1 and HUNT 2). Participants
      reached 77,224 and 65,599 persons, respectively (90.7% in HUNT 1 and 71.0% in
      HUNT 2). The participants responded to questionnaires, including questions on
      several diseases and impairments, as well as self-assessed health and
      psychological well-being. People with diabetes reported significantly lower well
      being than people with no reported diabetes in HUNT 1 as well as in HUNT 2.
      However, the relationship between diabetes and well-being was significantly
      weaker in HUNT 2 than in HUNT 1. Self-reported Subjective health, the feeling of
      being strong and fit, the use of Tranquilizers, and Psychological distress had
      improved between the two surveys, for people with diabetes compared to people
      with no reported diabetes. Other outcome variables - Calmness, Cheerfulness, and
      Life satisfaction - were only weakly related to diabetes, and the relationship
      did not change significantly from HUNT 1 to HUNT 2.

PMID- 15145326
TI  - Impact on mortality and incidence of end-stage renal disease of education and
      treatment at a diabetes center among patients with type 1 diabetes: comparison of
      two subgroups in the Japanese DERI cohort.
AB  - The aim of this study was to compare mortality and incidence of end-stage renal
      disease (ESRD) in patients with type 1 (insulin-dependent) diabetes who had
      attended a diabetes center with those who had not. The cohort consisted of a
      total of 1430 patients diagnosed with Type 1 diabetes at 18 years or younger, and
      between 1965 and 1979. This population-based cohort in Japan was subdivided into
      two groups: patients who had visited a large diabetes center in Tokyo (n=162) and
      those who had not (n=1212). Mortality and incidence of ESRD were compared between
      the two subgroups as of January 1, 1990. Crude mortality was 1.95 per 1000 person
      years (95% CI: 0.49-5.06) for those who had visited the center and 6.05 (4.86
      7.41) for those who had not. A multivariate Cox proportional hazard model showed
      that the patients who had visited the center were three times less likely to die
      (hazard ratio: 0.31, 95% CI: 0.10-0.98) than those who had not. Crude incidence
      of ESRD was 1.32 (0.22-4.09) and 5.86 (4.65-7.26) for those who had visited the
      center and for those who had not, respectively. After adjusting for covariates,
      the patients who had visited the center were five times less likely to develop
      ESRD (hazard ratio: 0.19, 0.05-0.78) than those who had not. Education and
      treatment of type 1 diabetes with an integrated management system under
      specialists and a multidisciplinary team appears to be associated with a better
      prognosis.

PMID- 15145325
TI  - A randomised trial of insulin on well-being and carer strain in elderly type 2
      diabetic subjects.
AB  - INTRODUCTION: Selected tablet-treated elderly type 2 subjects with very poor
      glycaemic control may experience improvements in well-being after starting twice
      daily insulin. In this study, the health status, mood, and treatment satisfaction
      of diabetic subjects with poor control on oral medication were assessed before
      and after being randomised to one of two insulin regimens. METHODOLOGY: Fifty
      seven type 2 subjects with poor glycaemic control (HBA(1c) 9.7%) were randomised
      to continue tablets (Group l), twice-daily isophane insulin (Group 2), or
      basal/bolus isophane/lispro insulin (Group 3). Health status, treatment
      satisfaction, and mood were measured at baseline, 1, 3, and 6 months. RESULTS:
      Mean HBA(1c) levels were lower in Groups 1 and 3 at 6 months (P<.02 and.03,
      respectively) but not Group 2 (P=.2). Mean health status scores did not differ
      between the groups at any time point. In Group 3, significant within-subject
      improvements occurred in six domains of the SF-36 at 1 month, four domains at 3
      months, and six domains at 6 months. There were no significant within-subject
      changes in health status scores in the other groups. Mean anxiety scores improved
      in both Groups 1 and 3 over 6 months, and mean depression scores also improved in
      Group 3 during the study. CONCLUSIONS: Small improvements in health status and
      mood may be associated with basal/bolus, but not twice-daily, insulin in elderly
      type 2 subjects. These effects may be independent of glycaemic control.

PMID- 15145327
TI  - The significance of the prepubertal diabetes duration for the development of
      retinopathy and nephropathy in patients with type 1 diabetes.
AB  - OBJECTIVE: A Danish nationwide prospective cohort of children and adolescents
      with type 1 diabetes was followed for 8 years to study the effect of the
      prepubertal duration of diabetes on early retinopathy and elevated albumin
      excretion rate (AER) (>20 microg/min). RESEARCH DESIGN AND METHODS: In 1989,
      blood glucose control (HbA(1c)) and AER was investigated in approximately 80% of
      all Danish children and adolescents with type 1 diabetes. A cohort of 339 young
      patients were restudied in 1995 including physical examination, demographic data,
      HbA(1c), AER, and fundus photography with central reading. Among the patients, a
      number of 304 had a prepubertal onset of diabetes defined as an onset age less
      than 11.7 years in girls and 12.9 years in boys. Microalbuminuria was defined as
      an AER of 20-150 microg min(-1) and macroalbuminuria as AER >150 microg min(-1)
      in two out of three timed overnight urine samples. RESULTS: At the follow-up in
      1995-1996, no patients were younger than 12 years of age. The prevalence of any
      level of retinopathy was 17.7% in the age group 12-15 years, 45.4% from 16 to 20
      years, and increased to 67.6% in patients more than 20 years of age. Diabetic
      retinopathy was significantly associated to poor long-term metabolic control
      (HbA(1c)) (P<.0001) and to diabetes duration both in patients with a prepubertal
      onset of disease as well as patients with a pubertal (P<.001) onset of disease.
      However, the pubertal diabetes duration contributed two times more than the
      prepubertal diabetes duration. Mean postpubertal diabetes duration to any
      retinopathy was significantly shorter (9.4 years) in patients with prepubertal
      onset of the disease compared to patients with postpubertal onset (11.8 years)
      (P=.0004). In total, the prevalence of elevated AER (>20 microg/min) increased
      from 4% in 1989 to 13% in 1995. None of the patients younger than 15 years of age
      had elevated AER, while the prevalence of elevated AER was about 14% from 15
      years of age and onwards. Elevated AER in 1995 was significantly related to long
      term metabolic control (P<.001) and elevated AER in the preceding years (P<.001)
      but was not correlated to diabetes duration neither before nor after the age of
      12 years. CONCLUSION: The prepubertal diabetes duration is significantly
      associated with the development of diabetic retinopathy. The period, however,
      contributes less compared to the years after puberty. In concert with other
      studies, we found no association between raised AER and diabetes duration. This
      may be explained by the fact that other factors are more significant and dilute
      the significance of diabetes duration. Nonetheless, it seems prudent to optimise
      blood glucose control irrespective of age.

PMID- 15145328
TI  - Homocysteine concentrations in type 2 diabetic patients with silent myocardial
      ischemia: a predictive marker.
AB  - BACKGROUND: Silent myocardial ischemia (SMI) is a frequent finding among diabetic
      patients. There are very few data on the relationship between homocysteine, which
      is a novel cardiovascular risk factor, and SMI in diabetic patients. We
      investigated whether plasma homocysteine has a predictive value for early
      diagnosis of SMI in type 2 diabetic patients. METHODS: One hundred and twenty
      diabetic patients and 25 control subjects were evaluated. Among diabetic
      patients, 29 had a history or clinical signs of coronary artery disease (CAD).
      All other patients who had normal ECGs and no history or clinical signs of CAD
      were screened by exercise test. Thirty-eight patients with maximal negative
      exercise test were labelled as CAD (-) diabetic patient group. Angiography was
      performed on patients who had positive exercise tests and among them 23 patients
      had angiographically documented SMI. RESULTS: CAD (+) and SMI groups had
      significantly higher serum homocysteine concentrations than CAD (-) and control
      groups (14.2+/-6.6, 15.7+/-7.8, 9.6+/-3.23, 9.3+/-2.25 micromol/l, respectively).
      In the SMI (+) diabetic group there was a significant correlation between serum
      homocysteine concentrations and creatinine, microalbuminuria and folic acid
      levels. Multiple regression analysis showed that homocysteine concentration was
      dependent on microalbuminuria, folic acid levels and presence or absence of
      ischemia. CONCLUSION: The present investigation shows an association of
      homocysteine with SMI in diabetic patients. Other prospective studies are needed
      to establish whether homocysteine levels can be used as a suitable marker for CAD
      screening in type 2 diabetic patients.

PMID- 15145329
TI  - Change in amputation rate in a Turkish diabetic foot population.
AB  - Diabetic foot, an important cause of morbidity and mortality, is an important
      economic problem in all countries. We examined the duration of diabetes, ratio of
      hospitalization, and the amputation rates of our diabetic foot patients between
      1996 and 2002 and compared the results with those obtained between 1985 and 1995.
      Medical reports of 117 patients with diabetic foot referred to Gazi University
      Medical Faculty between 1996 and 2002 were retrospectively analyzed. The mean age
      was 61.09+/-10.87 years and mean duration of diabetes was 16.14+/-9.44 years.
      Sixty-one patients were hospitalized and 56 patients were followed in our
      outpatient clinic. The mean duration of hospitalization was 45.00+/-18.74 (20-74)
      days in amputees and 28.95+/-11.61 (10-47) days in the nonamputees (P=.023). The
      mean age and duration of diabetes were significantly higher in amputees in the
      present group than that in the previous group. The amputation rate was
      significantly lower in the group studied between 1996 and 2002 compared to the
      group followed between 1985 and 1995 (9.4% vs. 21%, respectively, P<.001).
      Appropriate diabetes education and systematic follow-up in an outpatient clinic
      may delay preventable diabetic foot lesions and reduce the amputation rate.

PMID- 15145330
TI  - Mean platelet volume in Type 2 diabetic patients.
AB  - BACKGROUND: Altered platelet morphology and function have been reported in
      patients with diabetes mellitus. They are likely to be associated with the
      pathological processes and increased risk of vascular disease seen in these
      patients. We aimed to determine the mean platelet volume (MPV) in diabetics
      compared to nondiabetics, to see if there is a difference in MPV between
      diabetics with and without macro- and microvascular complications, and to
      determine the correlation between MPV and fasting blood glucose, glycosylated
      hemoglobin (HbA(1)c), patient age, and duration of diabetes, respectively.
      METHODS: We measured MPV in 145 consecutive Type 2 diabetic patients and 100
      nondiabetic control subjects without known coronary artery disease who had
      complete blood count on venous blood sample taken into tripotassium EDTA, using a
      Roche Minos cell counter and automatic blood counter (CELL-DYN 3500). The blood
      glucose level was measured by glucose oxidase method and HbA1c by calorimetrical
      method in the autoanalyser. Statistical evaluation was performed by SPSS for
      Windows statistics programme using multivariate logistical regression analysis,
      Student's t, and Pearson correlation tests. RESULTS: MPV was significantly higher
      and the mean platelet counts were significantly lower in diabetics compared to
      age- and sex-matched nondiabetic healthy controls [10.62+/-1.71 fl vs. 9.15+/
      0.86 fl (P=.00), 260.38+/-68.65 x 10(9)/l vs. 292.33+/-79.19 x 10(9)/l (P=.001)],
      respectively. CONCLUSIONS: Our results show significantly higher MPV in diabetic
      patients than in the nondiabetic controls. This suggests that platelets may play
      a role in the micro- and macrovascular complications of diabetic patients.

PMID- 15145331
TI  - Oxidative stress-induced up-regulation of the chloride channel and Na+/Ca2+
      exchanger during cataractogenesis in diabetic rats.
AB  - We have determined the abundance of the chloride channel, ClC-3, and Na(+)/Ca(2+)
      exchanger proteins in isolated rat lens cortex fiber cells by immunofluorescence
      method using polyclonal anti-ClC-3 antibodies and monoclonal antibodies against
      the canine cardiac Na(+)/Ca(2+) exchanger protein. These proteins were also
      quantified in the lens cortex of streptozotocin-injected rats by Western blots.
      Also, mRNA for ClC-3 was determined by Northern blot analysis. The isolated rat
      lens cortical fibers expressed basal levels of ClC-3 and Na(+)/Ca(2+) exchanger
      proteins. As compared to controls, the ClC-3 protein in the lens cortex of
      diabetic rats (blood glucose>400 mg%) increased by 2.5-fold in 7 days and 4.5
      fold in 14 days. However, the ClC-3 protein decreased to near-normal values in 40
      days. The changes in ClC-3 mRNA closely followed the protein levels. Similarly,
      as compared to controls, on Day 7, the Na(+)/Ca(2+) exchanger protein in the
      diabetic rat lens cortex increased by 3.5-fold and on Day14 by 5.5-fold.
      Subsequently, it decreased to control levels on Day 40. Treatment with the
      antioxidant, Trolox (2 mg/kg body weight), prevented the initial increase in ClC
      3 and Na(+)/Ca(2+) exchanger proteins. The up-regulation of ClC-3 and
      Na(+)/Ca(2+) exchanger proteins during the early stages of diabetes and its
      prevention by antioxidants suggests that the proteins regulating ion transport
      may have a pathophysiological role in the development of diabetic cataracts.

PMID- 15145333
TI  - Diabetic sclerosing lymphocytic lobulitis of the breast.
AB  - Diabetic sclerosing lymphocytic lobulitis of the breast (SLLB) as a complication
      of long standing diabetes is a benign disease without known tendency to malignant
      evolution. Clinically, it is characterized by solitary or multiple rock-hard
      discrete lesion(s) in one or both breasts, usually in a subareolar site, but may
      appear equally in any part of the breast. Mammographically and morphologically,
      this lesion simulates cancer. The lesion may recur after excision in the same
      site or in another location of the ipsilateral or the contralateral breast.
      Awareness of this entity, establishment of the diagnosis by open biopsy or by
      core needle biopsy may spare the need for repeated wide excisions and the
      resulting distortion of the breast architecture. The aim of this review is to
      arouse the awareness of the physicians and surgeons to this possibility when they
      find a similar lesion in the breast of a diabetic patient.

PMID- 15145334
TI  - Pneumothorax: an important complication of non-invasive ventilation in
      neuromuscular disease.

PMID- 15145332
TI  - Different effects of two alpha-glucosidase inhibitors, acarbose and voglibose, on
      serum 1,5-anhydroglucitol (1,5AG) level.
AB  - Serum 1,5-anhydroglucitol (1,5AG) is a useful glycemic marker in the control of
      diabetes; however, treated with alpha-glucosidase inhibitors (alpha-GIs),
      acarbose (Aca) and voglibose (Vog), it tends to show the discrepancy between
      serum 1,5AG and related glucose levels. Twenty patients were randomly assigned to
      adding Aca or Vog to the current treatment. We measured serum 1,5AG levels and
      other parameters of diabetic control before, 2 and 4 weeks after the alpha-GI
      treatment. We also measured urinary 1,5AG levels using gas chromatography/mass
      spectrometry (GC/MS). Glycated albumin, Hb(A1c), and fasting plasma glucose (FPG)
      levels were significantly decreased after 2 and 4 weeks of treatment, and the
      changes were similar in the two groups. Despite the similar urinary excretion of
      1,5AG and other glycemic parameters, serum 1,5AG level was significantly lower in
      the Aca group than in the Vog group (3.4+/-0.5 vs. 7.9+/-1.2 microg/ml, P<.005;
      mean+/-S.E.) at the period of 4 weeks. Even in the same glycemic level, the less
      increase of serum 1,5AG after treatment with Aca might be due to a reduction of
      intestinal 1,5AG absorption via inhibition of alpha-amylase that features Aca.

PMID- 15145335
TI  - Pneumothorax associated with long-term non-invasive positive pressure ventilation
      in Duchenne muscular dystrophy.
AB  - Long-term non-invasive positive pressure ventilation (NPPV) is effective for
      improving the quality of life and survival of neuromuscular patients. This
      treatment is usually easy to administer and severe complications have rarely been
      reported. We describe two cases in which the development of pneumothorax was
      associated with long-term NPPV administered to Duchenne muscular dystrophy
      patients. Given the wide scale utilization of chronic NPPV, we suggest that care
      givers and patients be made aware of this serious complication.

PMID- 15145336
TI  - Distinct phenotypes of congenital acetylcholine receptor deficiency.
AB  - We contrast the phenotypes associated with hereditary acetylcholine receptor
      deficiency arising from mutations in either the acetylcholine receptor epsilon
      subunit or the endplate acetylcholine receptor clustering protein rapsyn.
      Mutational screening was performed by amplification of promoter and coding
      regions by PCR and direct DNA sequencing. We identified mutations in 37
      acetylcholine receptor deficiency patients; 18 had acetylcholine receptor-epsilon
      mutations, 19 had rapsyn mutations. Mutated acetylcholine receptor-epsilon
      associated with bulbar symptoms, ptosis and ophthalmoplegia at birth, and
      generalized weakness. Mutated rapsyn caused either an early onset (rapsyn-EO) or
      late onset (rapsyn-LO) phenotype. Rapsyn-EO associated with arthrogryposis and
      life-threatening exacerbations during early childhood. Rapsyn-LO presented with
      limb weakness in adolescence or adulthood resembling seronegative myasthenia
      gravis. Awareness of distinct phenotypic features of acetylcholine receptor
      deficiency resulting from acetylcholine receptor-epsilon or rapsyn mutations
      should facilitate targeted genetic diagnosis, avoid inappropriate immunological
      therapy and, in some infants, prompt the rapid introduction of treatment that
      could be life saving.

PMID- 15145337
TI  - Prednisone reduces muscle degeneration in dystrophin-deficient Caenorhabditis
      elegans.
AB  - Duchenne muscular dystrophy is a degenerative muscular disease caused by
      mutations in the dystrophin gene. There is no curative treatment against Duchenne
      muscular dystrophy. In several countries, the steroid prednisone (or analogs) is
      prescribed as a palliative treatment. In the model animal Caenorhabditis elegans,
      mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative
      phenotype when they are associated with a mild MyoD mutation. This cheap and fast
      growing model of dystrophinopathy may be used to screen for molecules able to
      slow muscle degeneration. In a blind screen of approximately 100 compounds
      covering a wide spectrum of targets, we found that prednisone is beneficial to
      the C. elegans dystrophin-deficient muscles. Prednisone reduces by 40% the number
      of degenerating cells in this animal. This result is a proof-of-principle for the
      use of C. elegans as a tool in the search for molecules active against the
      effects of dystrophin-deficiency. Moreover, since C. elegans is not susceptible
      to inflammation, this suggests that prednisone exerts a direct effect on muscle
      survival.

PMID- 15145338
TI  - A case of childhood Pompe disease demonstrating phenotypic variability of
      p.Asp645Asn.
AB  - A six-year-old child presented at 8 months of age with proximal muscle weakness
      and mild cardiac hypertrophy. Some alpha-glucosidase activity was detected in
      muscle but not in fibroblasts. As none of the two pathogenic mutations,
      [c.1933G>A]+[c.2702T>A] (Asp645Asn/Leu901Gln), led to detectable alpha
      glucosidase activity upon expression in COS cells, the phenotype of the patient
      remained unexplained. A functionally comparable set of mutations,
      Asp645Asn/insGnt2243, was reported previously to cause classic infantile Pompe
      disease [Biochem Biophys Res Commun 244 (1998) 921]. We conclude that secondary
      genetic or environmental factors can be decisive for the phenotypic outcome of
      classic infantile versus childhood Pompe disease, when the acid alpha-glucosidase
      activity is extremely low.

PMID- 15145339
TI  - Mitochondrial dysfunction and rod-like lesions associated with administration of
      beta2 adrenoceptor agonist formoterol.
AB  - Formoterol, a selective beta 2-adrenoceptor agonist, has been introduced recently
      in the treatment of poorly controlled asthma. A patient is presented who
      developed myalgia and muscle weakness, associated with an elevation of creatine
      kinase (CK) during treatment with formoterol. Subsequent muscle biopsy
      demonstrated atrophic fibres lacking cytochrome C-oxidase and succinate
      dehydrogenase, suggestive of mitochondrial dysfunction. There were no
      inflammatory changes. Immunocytochemical analysis using antibodies to alpha
      actinin-2 and alpha-actinin-3 demonstrated positive staining of 'rod-like' bodies
      in atrophic fibres. Clinical and biochemical improvement occurred following
      withdrawal of formoterol. Possible mechanisms involved in the development of
      myopathy are explored.

PMID- 15145340
TI  - The dropped head sign: an unusual presenting feature of myasthenia gravis.

PMID- 15145341
TI  - Multifocal motor neuropathy presenting as chronic progressive proximal leg
      weakness.
AB  - We report on a 47-year-old man with a 12-year history of progressive and
      ultimately severe proximal weakness of his right lower limb. Motor conduction
      block at the unaffected tibial nerve and positive IgM antibodies against GM1
      gangliosides lead us to suggest a diagnosis of oligosymptomatic multifocal motor
      neuropathy. He rapidly responded to intravenous immunoglobulins, with complete
      remission lasting 4 weeks, and had a repeated treatment response to intravenous
      immunoglobulins during subsequent exacerbations. The proximal involvement may
      represent another unusual clinical manifestation of multifocal motor neuropathy.

PMID- 15145342
TI  - Lisa Welander and Eric Kugelberg--two Swedish myologists in the footsteps of
      Edward Meryon. The Edward Meryon lecture, the Meryon Society, Oxford 2003.

PMID- 15145343
TI  - 118th ENMC International Workshop on Advances in Myotubular Myopathy. 26-28
      September 2003, Naarden, The Netherlands. (5th Workshop of the International
      Consortium on Myotubular Myopathy).

PMID- 15145345
TI  - miRNAs on the move: miRNA biogenesis and the RNAi machinery.
AB  - Recent advances have led to a more detailed understanding of RNA interference and
      its role in microRNA biogenesis and function. Primary microRNA transcripts are
      processed by the RNaseIII nuclease, Drosha, and are exported from the nucleus by
      Exportin-5. Dicer cleaves microRNAs into their mature forms, which can be
      incorporated into effector complexes that mediate gene silencing activities. The
      3' two-nucleotide overhang structure, a signature of RNaseIII cleavage, has been
      identified as a critical specificity determinant in targeting and maintaining
      small RNAs in the RNA interference pathway. MicroRNA functional analyses and
      genetic and biochemical interrogation of components of the pathway are starting
      to provide a glimpse at the range of biological processes and phenomena regulated
      by RNA interference.

PMID- 15145346
TI  - Regulation of heterochromatin by histone methylation and small RNAs.
AB  - Heterochromatin mediates various nuclear processes including centromere function,
      gene silencing and nuclear organization. Although it was discovered nearly 75
      years ago, the pathways involved in heterochromatin establishment, assembly and
      epigenetic maintenance have been elusive. Recent reports have demonstrated that
      distinct and novel chromatin-associated factors, including DNA, RNA and histone
      modifications, are involved in each of these events. These new findings define a
      novel conserved mechanism of heterochromatin formation that is likely to have an
      impact on all eukaryotic silencing pathways.

PMID- 15145347
TI  - Polycomb complexes and silencing mechanisms.
AB  - Advances in the past couple of years have brought important new knowledge on the
      mechanisms by which Polycomb-group proteins regulate gene expression and on the
      consequences of their actions. The discovery of histone methylation imprints
      specific for Polycomb and Trithorax complexes has provided mechanistic insight on
      how this ancient epigenetic memory system acts to repress and indicates that it
      may share mechanistic aspects with other silencing and genome-protective
      processes, such as RNA interference.

PMID- 15145348
TI  - Recent advances in X-chromosome inactivation.
AB  - X inactivation is the silencing one of the two X chromosomes in XX female
      mammals. Initiation of this process during early development is controlled by the
      X-inactivation centre, a complex locus that determines how many, and which, X
      chromosomes will be inactivated. It also produces the Xist transcript, a
      remarkable RNA that coats the X chromosome in cis and triggers its silencing.
      Xist RNA coating induces a cascade of chromatin changes on the X chromosome,
      including the recruitment of Polycomb group proteins. This results in an inactive
      state that is initially labile, but may be further locked in by epigenetic marks
      such as DNA methylation. In mice, X inactivation has recently been found to be
      much more dynamic than previously thought during early pre-implantation
      development. The paternal X chromosome is initially inactivated in all cells of
      cleavage-stage embryos and then selectively reactivated in the subset of cells
      that will form the embryo, with random X inactivation occurring thereafter.

PMID- 15145349
TI  - Does looping and clustering in the nucleus regulate gene expression?
AB  - There has been considerable interest in the way that chromatin is spatially
      organised within the cell nucleus and how that may relate to gene expression and
      its control. New molecular techniques have identified looped chromatin domains at
      the mammalian beta-globin and the Drosophila hsp70 loci. Looped domains may
      insulate chromatin from the influence of neighbouring domains, and the bases of
      loops may also act to concentrate proteins locally within the nucleus. The
      spatial clustering of sequences from the Drosophila bithorax complex, located in
      trans, has also been demonstrated. An emerging theme is that bringing DNA and
      proteins together within a defined sub-region of the nuclear volume facilitates
      both the activation and the repression of gene expression. Nuclear compartments
      may also be involved in the post-translational modification of proteins by
      sumoylation and ubiquitylation.

PMID- 15145350
TI  - Recent highlights of RNA-polymerase-II-mediated transcription.
AB  - Considerable advances into the basis of RNA-polymerase-II-mediated
      transcriptional regulation have recently emerged. Biochemical, genetic and
      structural studies have contributed to novel insights into transcription, as well
      as the functional significance of covalent histone modifications. New details
      regarding transcription elongation through chromatin have further defined the
      mechanism behind this action, and identified how chromatin structure may be
      maintained after RNAP II traverses a nucleosome. ATP-dependent chromatin
      remodeling complexes, along with histone chaperone complexes, were recently
      discovered to facilitate histone exchange. In addition, it has become
      increasingly clear that transcription by RNA polymerase II extends beyond RNA
      synthesis, towards a more active role in mRNA maturation, surveillance and export
      to the cytoplasm.

PMID- 15145351
TI  - New perspectives on connecting messenger RNA 3' end formation to transcription.
AB  - Recent advances in understanding the molecular mechanism of mRNA 3' end cleavage
      and polyadenylation have uncovered an unanticipated involvement of this process
      in the regulation of the transcriptional apparatus on its chromatin template.
      Thus, newly defined factors associated with mRNA 3' end formation are also
      connected with initiation of transcription, suggesting a close collaboration
      between the initiation and termination phases of transcription. Furthermore
      several of these factors are involved in setting up appropriate chromatin
      structure to facilitate efficient transcriptional elongation and termination.

PMID- 15145352
TI  - The ever-increasing complexities of the exon junction complex.
AB  - Over the past decade many studies have revealed a complex web of interconnections
      between the numerous steps required for eukaryotic gene expression. One set of
      interconnections link nuclear pre-mRNA splicing and the subsequent metabolism of
      the spliced mRNAs. It is now apparent that the means of connection is a set of
      proteins, collectively called the exon junction complex, which are deposited as a
      consequence of splicing upstream of mRNA exon-exon junctions.

PMID- 15145353
TI  - mRNA export: an assembly line from genes to nuclear pores.
AB  - mRNAs are transported from the nucleus to the cytoplasm by a machinery conserved
      from yeast to humans. Previous studies showed that mRNA export factors are loaded
      on nascent mRNAs during elongation, coupling transcription to export. More
      recently identified mRNA export factors connect transcription initiation to the
      export machinery associated with nuclear pores, and potentially tether active
      genes to the nuclear periphery. Furthermore, a newly identified link between the
      nuclear exosome and the transcription, 3'-end formation and export machineries
      suggests that early messenger ribonucleoprotein complex (mRNP) assembly is co
      transcriptionally monitored. Moreover, inefficient mRNP assembly impairs
      transcription elongation, indicating tight interdependence of these processes.
      Finally, nuclear retention of unspliced mRNAs by the perinuclear Mlp proteins
      reveals a novel mechanism of mRNP surveillance prior to export.

PMID- 15145354
TI  - Nonsense-mediated mRNA decay: terminating erroneous gene expression.
AB  - Nonsense-mediated mRNA decay is a surveillance pathway that reduces errors in
      gene expression by eliminating aberrant mRNAs that encode incomplete
      polypeptides. Recent experiments suggest a working model whereby premature and
      normal translation termination events are distinct as a consequence of the
      spatial relationship between the termination codon and mRNA binding proteins, a
      relationship partially established by nuclear pre-mRNA processing. Aberrant
      termination then leads to both translational repression and an increased
      susceptibility of the mRNA to multiple ribonucleases.

PMID- 15145355
TI  - mRNA localisation gets more complex.
AB  - Recent advances in techniques for visualising mRNA movement in living cells have
      led to rapid progress in understanding the mechanism of mRNA localisation in the
      cytoplasm. There is an emerging consensus that in many cases the mRNA signals
      that determine intracellular destination are more complex and difficult to define
      than was first anticipated. Furthermore, the transacting factors that interpret
      the mRNA signals are numerous and their combinations change during the life of an
      mRNA, perhaps allowing the selection of many sub-destinations in the cell.
      Lastly, an emerging theme over the past few years is that many proteins that
      determine the destinations of mRNAs are recruited on nascent transcripts in the
      nucleus. They often function in many different processes in the biogenesis of
      mRNA and probably act in concert to provide specificity.

PMID- 15145357
TI  - Dynamics of nuclear pore complex organization through the cell cycle.
AB  - In eukaryotic cells, all macromolecules that traffic between the nucleus and the
      cytoplasm cross the double nuclear membrane through nuclear pore complexes
      (NPCs). NPCs are elaborate gateways that allow efficient, yet selective,
      translocation of many different macromolecules. Their protein composition has
      been elucidated, but how exactly these nucleoporins come together to form the
      pore is largely unknown. Recent data suggest that NPCs are composed of an
      extremely stable scaffold on which more dynamic, exchangeable parts are
      assembled. These could be targets for molecular rearrangements that change
      nuclear pore transport properties and, ultimately, the state of the cell.

PMID- 15145358
TI  - Aging and nuclear organization: lamins and progeria.
AB  - The discoveries of at least eight human diseases arising from mutations in LMNA,
      which encodes the nuclear A-type lamins, have revealed the nuclear envelope as an
      organelle associated with a variety of fundamental cellular processes. The most
      recently discovered diseases associated with LMNA mutations are the premature
      aging disorders Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner's
      syndrome. The phenotypes of both HGPS patients and a mouse model of progeria
      suggest diverse compromised tissue functions leading to defects reminiscent of
      aging. Aspects of the diseases associated with disrupted nuclear envelope/lamin
      functions may be explained by decreased cellular proliferation, loss of tissue
      repair capability and a decline in the ability to maintain a differentiated
      state.

PMID- 15145356
TI  - Regulation of local mRNA translation.
AB  - Regulated local mRNA translation is one mechanism cells employ to concentrate
      proteins in particular locations. However, cells use many different strategies to
      accomplish this task; for example, some mRNAs are destroyed in regions where they
      are not wanted, other mRNAs are repressed in areas where their translation would
      be deleterious, and yet other mRNAs are transported, in a quiescent state, to the
      sites where their translation is activated. The importance of local translation
      cannot be overstated, for, depending on the species or cell type, it is required
      for cell division, establishment of mating type, development and memory
      formation.

PMID- 15145359
TI  - DNA damage checkpoint and repair centers.
AB  - In eukaryotes, recombinational repair is choreographed by multiprotein complexes
      that are organized into focal assemblies. These foci are highly dynamic giga
      dalton structures capable of simultaneously repairing multiple DNA lesions.
      Moreover, the composition of these repair centers depends on the nature of the
      DNA lesion and is tightly coordinated with progression of the cell cycle.
      Components of DNA repair centers are regulated by post-translational
      modifications such as phosphorylation, ubiquitination and sumoylation. Repair
      foci progress through four distinct stages: first, DNA damage recognition and
      binding of DNA ends by the Mre11 complex and Ku70/80; second, end-processing and
      binding of single-stranded DNA by replication protein A, which recruits
      checkpoint proteins; third, recombinational repair during S and G(2) phase; and
      fourth, disassembly of foci and resumption of the cell cycle.

PMID- 15145361
TI  - The role of the maternal-fetal medicine specialist in high-risk obstetric care.
AB  - The maternal-fetal medicine (MFM) specialist is a member of the health care team
      who possesses expertise in the management of the high-risk pregnancy. The MFM
      specialist has advanced knowledge of obstetric, medical, genetic, and surgical
      complications of pregnancy and the effects of complications on the mother, fetus,
      and newborn. The MFMspecialist may function as consultant, comanager, or direct
      care provider and may be equally comfortable in antepartum ambulatory, inpatient
      obstetric, and critical care settings. As the female population increases, the
      number of MFM specialists also is expected to grow.

PMID- 15145360
TI  - Does protein synthesis occur in the nucleus?
AB  - Although it is universally accepted that protein synthesis occurs in the
      cytoplasm, the possibility that translation can also take place in the nucleus
      has been hotly debated. Reports have been published claiming to demonstrate
      nuclear translation, but alternative explanations for these results have not been
      excluded, and other experiments argue against it. Much of the appeal of nuclear
      translation is that functional proofreading of newly made mRNAs in the nucleus
      would provide an efficient way to monitor mRNAs for the presence of premature
      termination codons, thereby avoiding the synthesis of deleterious proteins. mRNAs
      that are still in the nucleus-associated fraction of cells are subject to
      translational proofreading resulting in nonsense-mediated mRNA decay and perhaps
      nonsense-associated alternate splicing. However, these mRNAs are likely to be in
      the perinuclear cytoplasm rather than within the nucleus. Therefore, in the
      absence of additional evidence, we conclude that nuclear translation is unlikely
      to occur.

PMID- 15145362
TI  - Multiorgan dysfunction in the perinatal patient.
AB  - MODS is a rare but potentially lethal complication of pregnancy. Pregnancy
      induces physiologic changes in all major maternal organ systems that mimic early
      changes seen in SIRS and MODS. When a potentially life-threatening event occurs,
      such as hemorrhage,sepsis, or severe preeclampsia, the perinatal nurse must
      monitor subtle changes in maternal and fetal status and intervene to optimize
      maternal status.

PMID- 15145363
TI  - Isoimmunization in pregnancy.
AB  - Isoimmunization to the Rh(D) antigen and to other red cell antigens remains a
      potentially severe complication of pregnancy. Although management of this
      complication is performed best by perinatologists, nurses often are the ones who
      provide further explanations, answer questions, and assist patients who are
      trying to understand complex physiology and management plans. Nurses should
      understand current controversies related to isoimmunization and function as
      patient advocates if needed. To meet these demands, nurses must continue to
      refresh their knowledge of isoimmunization and its potential complications and
      review ever-changing management regimens.

PMID- 15145364
TI  - Myocardial infarction in the obstetric patient.
AB  - Myocardial infarction (MI) during pregnancy is a rare event, occurring in 1 in
      10000 pregnancies. Mortality rates range from 30% to 50% depending on the
      maternal clinical picture. Myocardial care options and their suitability for use
      during pregnancy are summarized. Two case studies are presented with different
      clinical courses resulting indifferent delivery methods. The multidisciplinary
      approach to each unique situation is described in detail as are common
      complications post MI.

PMID- 15145365
TI  - Amniotic fluid embolism.
AB  - Amniotic fluid embolism (AFE) (also known as anaphylactoid syndrome of
      pregnancy)is a catastrophic condition that occurs during pregnancy or shortly
      after delivery. It is found throughout the world in developed and undeveloped
      countries and occurs at an incidence of between 1 in 80000 live births. In the
      United States, AFE occurs in 1 in 20000 to 80000 deliveries.

PMID- 15145366
TI  - Maternal mortality--a review of current trends.
AB  - Pregnancy-related maternal deaths, although rare,are higher than the public
      health goal of no more than 3 per 100000 live births [5,6]. Achievement of this
      goal mandates complete and consistent reporting of all maternal deaths to
      identify causes of death accurately and correct underreporting [2]. Racial
      disparity between white and African American women must be reduced. Further
      research is needed to identify the factors contributing to the higher mortality
      rates in the African American population. Risk factors currently identified with
      adverse perinatal outcomes do not explain the differences in mortality rates
      adequately. Perinatal nurses and primary care providers should take an active
      role in identifying current trends in causes of matemal mortality. The population
      of women encountered daily in perinatal units is changing, with an increasing
      number of pregnancies complicated by preexisting and pregnancy-related medical
      conditions. Caring for these women within the framework that pregnancy is a
      normal, physiologic state can lead to complacency and increase the probability of
      missing early signs of maternal decompensation from an undiagnosed cardiac
      lesion, because shortness of breath and decreased exercise tolerance are
      considered normal changes as the pregnancy advances. Common complaints of
      pregnancy often mimic early signs of cardiopulmonary compromise, delaying an
      accurate diagnosis. The perinatal nurse must be aware of the early signs of an
      impending cardiopulmonary arrest. If recognized. subtle changes in levels of
      mentation, increasing pulse and respiratory rates, and changes in blood pressure
      lead to earlier interventions to correct maternal hemodynamic status and possibly
      prevent cardiopulmonary collapse. To further complicate the issue, the mindset in
      perinatal units often is, "It can't happen here" or "We don't have codes in
      obstetrics."Perinatal units should practice emergency drills, including
      management of eclampsia, hemorrhage, and cardiopulmonary arrest. Rehearsal of the
      emergency situation helps decrease anxiety for the staff and increase response
      times. The goal of the irreducible minimum for prevent-able maternal deaths is
      one to strive for in today's perinatal practice. Active surveillance to identify
      causes of maternal mortality allows for initiation of early interventions to
      minimize maternal compromise, thereby decreasing preventable deaths.

PMID- 15145367
TI  - Placenta accreta: a case study.
AB  - Placenta accreta is a placenta implantation that results in an abnormal firm
      adherence to the uterine wall. The placenta is attached directly to the
      myometrium. Placenta increta extends in the myometrium into the uterine
      musculature. The most severe form of accreta is percreta. In placenta percreta,
      penetration of the trophoblast through the myometrium possibly occurs into the
      peritoneum and invades adjunct organs.

PMID- 15145368
TI  - Fetal assessment in the adult intensive care unit.
AB  - Ideally the clinical management of a critically ill pregnant woman is based on a
      collaborative approach with members of the ICU and perinatal team each
      contributing their expertise to promote the best out-come for the mother and
      baby. The interdisciplinary team also should include anesthesia providers and
      neonatal specialists. The physical space (ICU or labor and delivery unit) is less
      important than the quality and coordination of the care and treatment. The
      responsibility for fetal assessment when the woman is critically ill should rest
      with those who have this expertise. Working together provides the best
      opportunity for optimal outcomes.

PMID- 15145369
TI  - Use of evidence-based practice in the neonatal intensive care unit.
AB  - The process change described is an ongoing project in the HICN. Through this
      process we found that developmentally sensitive care can be accomplished as early
      as the time of birth by minimizing trauma to ELBW infants, keeping them nested
      with minimal handling. This also supports the goal for this population of
      minimizing cold stress and its effects. Gentle ventilation can be achieved in the
      delivery room by understanding physiology and the effects of ventilation on the
      ELBW lung tissue.

PMID- 15145370
TI  - The use of nitric oxide in neonatal care.
AB  - Knowledge of NO and its role in the human body currently is limited. Further
      scientific research involving this unique molecule will expand its clinical
      usefulness. It is an exciting era in research,involving numerous body processes
      and systems. The initial work on pulmonary vascular response in newborns who have
      PPHN has opened the door to seemingly endless possibilities involving many
      aspects of health.

PMID- 15145372
TI  - Ethical issues in the neonatal intensive care unit.
AB  - The case of Baby Y presented a difficult and complex ethical dilemma for the
      family and the staff involved. The issues of religious beliefs and law, up
      holding these beliefs in the center of a religious community, financial concerns,
      and health care workers disagreeing about carrying out treatments made this case
      one that few will forget. When asked after Baby Y died how they felt, many
      members of the staff answered that it should not have gone on as long as it did
      and that they learned a lot from the family and the experience. Palliative care
      has been well associated with the adult cancer population in the form of hospice
      care. It is the hope that this well-integrated aspect of care crosses over to the
      NICU population. Many of the patients in the types of cases mentioned previously
      stay in the NICU for extended periods of time until a decision is made clear or
      the infant expires on his own time. The hustle and bustle of a busy, open, and
      not-so-private NICU is not the place for this to take place. The NICU should have
      a designated place where these infants can be cared for better in a more family
      centered and staff-friendly environment. Pain management is another important
      aspect of palliative care. Comfort of the infant is of utmost importance, as it
      helps the family believe the suffering is under control. During the last few days
      or weeks of life, the family should have time that is peaceful and restful, and,
      eventually, the infant should have a pain-free death.Lastly, a part of the
      palliative care philosophy and approach includes providing treatments that may ap
      pear to prolong the inevitable but in fact help the process along to resolution.
      In the case of Baby Y, surgery to repair some of the defects may have allowed her
      to go home with her family and spend her short life with them. This was the wish
      of the mother,especially, and it never happened. It may well be the"what if" she
      continues to ask for the rest of her life.

PMID- 15145371
TI  - Neonatal jaundice: physiologic variation or pathologic process.
AB  - Neonatal hyperbilirubinemia and jaundice affect approximately 60% of the 4
      million newborns in the United States each year. Jaundice results from bilirubin
      deposition in the skin and mucous membranes, becoming clinically visible at a
      serum bilirubin level of 5 to 7 mg/dL. At a higher but undefined level, bilirubin
      may deposit in the brain where it can cause transient dysfunction or permanent
      neurologic impairment.

PMID- 15145374
TI  - History of human parasitic diseases.
AB  - Humans are afflicted by a number of diseases caused by parasitic protozoa and
      helminth worms. The first records of these ancient associations come from studies
      on archeologic material and the writings of the Greek, Egyptian, and Roman
      empires but it was not until the theory of spontaneous generation had been
      disproved in the nineteenth century that it became possible to incriminate
      parasites in the etiologies of a number of diseases that had hitherto been
      enigmatic. The golden age of parasitology was the nineteenth century when most of
      the life cycles of parasites were accurately described for the first time. The
      history of parasitology is not yet complete and new diseases are still being
      discovered.

PMID- 15145375
TI  - Malaria: from prehistory to present.
AB  - Malaria is a protozoan (Plasmodium) infection transmitted by the biting female
      Anopheles mosquito. The disease affects approximately 40% of the world's
      population, and an estimated 50 to 70 million Western travelers are exposed to
      malaria infection annually. Malaria and travelers are inextricably linked since
      the dawn of time. Malaria owes its distribution worldwide to human travelers, and
      travelers are linked with the discovery, refinement, and development of several
      antimalarial drugs. In the year 2003 the genomes for humans, mosquito, and
      Plasmodium have been completed, but no malaria vaccine is available as yet.

PMID- 15145376
TI  - Schistosomiasis (bilharziasis): from antiquity to the present.
AB  - The history of schistosomiasis is a continuous saga of discovery and
      disappointments. A lot is known and functional genomics bring the hope for better
      tools, but the infection and its disease sequelae still sap the energy of
      millions worldwide. The successes in its control are few, and the failures are
      enormously challenging to the scientific and public health communities and to
      decision makers globally. This article examines the fundamental milestones in
      understanding the parasite-host interaction over approximately 5 millennia of
      recorded history and sketches the main features of progress in the past few
      decades without attempting a detailed assessment.

PMID- 15145377
TI  - Discovery and clinical importance of the filariases.
AB  - Macrofilariae have been recognized for many millennia. Microfilariae were,
      however, not demonstrable until microscopy attained an advanced degree of
      perfection. Demonstration of the mode of transmission of the various filariases
      (Wuchereria bancrofti, Onchocerca volvulus, and Loa loa), dominated by Manson's
      work on lymphatic filariasis, constitutes one of the most exciting phases inhuman
      parasitology.

PMID- 15145378
TI  - History of sleeping sickness (African trypanosomiasis).
AB  - Infections with subspecies of the protozoan parasite Trypanosoma brucei cause
      important wasting diseases in Africa (nagana in cattle and sleeping sickness in
      humans). These diseases were little known until the end of the nineteenth century
      when serious epidemics of nagana were reported and raised concern among the
      colonial powers. The early history of sleeping sickness revolves around the
      discovery of the causative organism, its mode of transmission,and its life cycle
      in the tsetse fly. The history continues into the twentieth century with the
      discovery of how the parasites evade the immune response, frustrating the
      development of a vaccine; the failure to develop cheap and effective drugs; and
      the development of alternative approaches to control the tsetse fly vector.

PMID- 15145379
TI  - The discovery of Chagas disease: progress and prejudice.
AB  - The discovery of Chagas disease makes an extraordinary story. It encompasses the
      pinnacle of scientific achievement and has some unique features. In addition,
      there is a background story line of controversy, jealousy, and power politics.
      This article provides a synopsis of all these fascinating aspects of the
      discovery.

PMID- 15145380
TI  - Infectious diarrhea in history.
AB  - Throughout history, infectious diarrhea has been associated with crowding, poor
      sanitation, and war. Although descriptions of infectious diarrhea exist in the
      earliest records of civilization, effective measures for prevention were not
      widely or consistently used until the modern era of active public health
      promotion. Advances in the understanding of etiologies and therapies have
      revolutionized prognosis; however, constant vigilance against lapses in public
      health is necessary to prevent outbreaks of disease.

PMID- 15145381
TI  - Yellow fever in the Americas.
AB  - Dutch slave traders brought yellow fever to the Americas from Africa during the
      mid-seventeenth century. For the next two and a half centuries, the disease
      terrorized seaports throughout the Americas. Proof of the mosquito hypothesis was
      delayed because of two aspects of the disease: patients are viremic only during
      the first several days of clinical illness, and most mosquitoes require about 2
      weeks of viral incubation before becoming infectious. Control of Aedes aegypti in
      urban centers failed to eliminate the disease because of its transmission by tree
      hole-breeding mosquitoes that spend their winged lives mainly in forest canopies.
      Yellow fever continues to be a significant public health problem in parts of
      South America and Africa.

PMID- 15145382
TI  - The major infectious epidemic diseases of Civil War soldiers.
AB  - Two thirds of the 600,000 deaths of Civil War soldiers were caused by disease.
      Physicians during the war kept detailed records and reports, which were
      tabulated, discussed in detail, and published after the war. These records
      include case histories, autopsy descriptions, photographs, and photomicrographs;
      they are the best records of the medical experiences of any of America's wars,
      even those in the twentieth century. Because the Civil War occurred just before
      the discoveries of bacteriology, these records are of particular historical
      interest.

PMID- 15145383
TI  - How the mighty have fallen: fatal infectious diseases of divine composers.
AB  - Their music is immortal, but famous composers of the last centuries were not. Up
      to 50 years ago, microbial infections were a major cause of mortality and showed
      composers no special mercy. They died of various infectious diseases. By
      application of modern intensive care measurements and effective antibiotics, many
      of them would have been saved. Disease and painful death brought the work of
      these divine artists to the level of immortal creations that both inspire and
      astonish the mortal audience.

PMID- 15145384
TI  - Impact of infectious diseases on war.
AB  - Wartime epidemics of infectious diseases have decimated the fighting strength of
      armies, caused the suspension and cancellation of military operations, and
      brought havoc to the civil populations of belligerent and nonbelligerent states.
      This article summarizes the principal factors that have contributed to the spread
      of infectious diseases in past wars and reviews the associated demographic losses
      in military and civil populations. Drawing on the detailed epidemiologic records
      for the United States Army, case studies of the spread of infectious diseases in
      relation to military mobilization are presented for the American Civil War,
      Spanish-American War,and World War I. The article concludes with a brief overview
      of infectious disease activity in high- and low-intensity conflicts of the late
      twentieth and early twenty-first centuries.

PMID- 15145385
TI  - The evolution of HIV and its consequences.
AB  - Since the beginning of the AIDS epidemic in 1981, HIV-1 has demonstrated an
      amazing ability to mutate. HIV-1 was introduced into the human population in the
      early to mid twentieth century in central Africa. During ensuing decades, this
      extraordinary mutational capacity has resulted in the circulation of HIV-1
      strains that are quite different from one another, yet still remarkably
      pathogenic. The potential impact of this viral diversity on treatment,
      monitoring,and vaccine development is discussed.

PMID- 15145387
TI  - Rodent husbandry and care.
AB  - This article reviews the husbandry, care and normal behavioral preferences of pet
      rats and mice. It covers recognition of signs of pain, illness and abnormal
      responses, and describes necessary skills such as handling, blood collection and
      drug administration. Animal-human responses in owning and caring for rats and
      mice are considered. Included is advice on suitability of pet rats with children,
      neutering and dental examinations. The conclusion lists recommended textbooks,
      pet owner manuals, instructional CDs, and websites.

PMID- 15145388
TI  - Ferret care and husbandry.
AB  - Convivial and playful, the ferret has cohabited with humans for hundreds of
      years. Maintenance of this mustelid's health and quality of life is paramount for
      the endurance of the human-animal bond. This review article for veterinary care
      givers, veterinarians, and staff, encompasses discussions on: husbandry, clinical
      techniques, prevalent diseases, history taking, physical examination,
      vaccination, and pain recognition. This article also enables the veterinary
      community to contribute to the care and welfare of ferret patients by offering
      facts to distinguish these animals from dogs and cats.

PMID- 15145389
TI  - Hedgehog care and husbandry.
AB  - An understanding of the unique behavior of hedgehogs is discussed,and is
      instrumental in approaching their nutrition, husbandry, and medical care.
      Physical examination, sample collection, anesthesia,hospitalization, and common
      signs of illness are presented.

PMID- 15145390
TI  - Prairie dog care and husbandry.
AB  - The species of prairie dog most commonly found in the pet trade is the black
      tailed prairie dog, Cynomus ludovicianus. These prairie dogs are active, playful,
      and strong rodents that can make wonderful, affectionate pets when they are
      properly socialized and given attention. However, with a life span of 8 to 12
      years, prairie dogs require a lot of care and a long-term commitment. Prairie
      dogs live in colonies; thus, they are highly social animals. Potential owners
      should understand a prairie dog's need for attention before adopting one.

PMID- 15145392
TI  - Rabbit care and husbandry.
AB  - This article provides information for the veterinary staff to be better prepared
      to care for the special needs of rabbit patients as they are presented in
      increased frequency for veterinary care. Housing, nutrition,restraint, and
      recognizing illness are covered in detail. Descriptions of techniques for blood
      collection, oral medication administration, and injection sites are included.
      Preventive care recommendations for examinations from first visit to geriatric
      visits are outlined as well as indications for spaying and neutering. Also
      provided are lists that will aid the veterinary staff in providing instructions
      when the appointment is made, recommendations for boarding, surgical, and
      anesthetic considerations and clinical signs that are associated with pain in
      rabbits.

PMID- 15145391
TI  - Marsupial care and husbandry.
AB  - Although startlingly different in anatomy and physiology from the placental
      mammals common to private veterinary practice, clinical care for marsupial
      mammals can be approached from similar perspectives. Marsupials remain
      undomesticated animals with challenging needs in diet and care that must consider
      their native environment to be successful. As wild animals, veterinary care and
      clinical problems of marsupials as pets can present from sources of stress,
      restraint, and husbandry. Veterinary professional scan prevent many of these
      concerns by advising caretakers on appropriate care and feeding of these species.

PMID- 15145393
TI  - Avian care and husbandry.
AB  - Birds are becoming more popular as pets, and the need for veterinary
      professionals to learn more about these pets is crucial. This article introduces
      the veterinary staff to basic information required to provide high-quality care
      to avian patients. High-quality nutrition for a variety of species and ages is
      included in this article. The importance of proper husbandry and intellectual
      stimulation with toys is also discussed. Special emphasis is placed on
      instructions for clients when making appointments, as well as recognizing signs
      of illness for both clients and veterinary staff. Capture, restraint, and sample
      collection are an important part of this article, as well as medication
      administration, anesthesia, supportive care, preventive care and grooming. A
      variety of aspects concerning the care of the avian patient are covered for the
      benefit of the client and veterinary technician.

PMID- 15145395
TI  - Nursing care of lizards.
AB  - This article should introduce to the veterinary staff some of the basic
      information that is required to provide high-quality medicine to lizards. This
      article begins with a brief introduction to lizards and their husbandry,
      including caging, lighting, humidity, and diet.Making appointments for lizards,
      taking a history, manual restraint,venipuncture, fecal sampling, catheterization,
      medications,administering fluids, giving injections, radiology, and anesthesia
      are all detailed for veterinary technicians and veterinary animal care staff.
      Each section details differences between lizards and typical mammalian patients
      while trying to emphasize the common approach to both groups of animals.

PMID- 15145394
TI  - Guinea pig and chinchilla care and husbandry.
AB  - This article reviews breeds and coat colors of guinea pigs and chinchillas, their
      husbandry, care and anatomy. The unusual reproductive physiology and reproductive
      diseases of these animals are described. We cover nutrition, the potential for
      disease on poor diets, and the vocalization of hystricomorph rodents. Skills such
      as handling, sexing, blood collection and drug administration, including
      antibiotic toxicity are described. The conclusion lists recommended textbooks,
      pet owner manuals, and websites.

PMID- 15145396
TI  - Pet fish care and husbandry.
AB  - This article guides the technician through the basic principles of fish health.
      Nutrition, including the proper storage of fish foods, is discussed,as are the
      varying dietary needs of fish. The ability to recognize water-quality problems is
      emphasized, especially the conditions that commonly result in high mortality.
      Collection of specimens for microscopic examination or other diagnostic tests is
      explained.

PMID- 15145397
TI  - Snake care and husbandry.
AB  - The snake has long been a contradictory species; you either love them or hate
      them. In the United States, these reptiles are popular pets. There is also a
      significant amount of energy placed into developing captive breeding programs to
      produce different color morphs for many species. In some cases, such as the ball
      pythons (Pythonregius), these color morphs can sell for 20,000 dollars to 30,000
      dollars each. In comparison to domestic mammals, snakes are long-lived. It is not
      uncommon for corn snakes (Elaphe guttata guttata) to live for 15 to 25 years and
      for ball pythons to live 35 to 45 years. Because of the longevity and value of
      these animals, more snakes are being presented to the veterinarian to manage
      medical and surgical problems,as well as for routine medical care. Veterinary
      personnel working with snakes should familiarize themselves with the specific
      husbandry and medical requirements of these animals so that they can make
      informed decisions regarding their management.

PMID- 15145398
TI  - Turtle care and husbandry.
AB  - Chelonians (turtles, tortoises, and terrapins) are not as well represented in
      private reptile collections as are snakes and lizards. Thismay be due in part to
      the fact that they often require more space and time for proper care.
      Nonetheless, they are still popular pets.Unfortunately, many people are not aware
      of what constitutes proper care for these animals. This article will discuss
      basic captive husbandry and nutrition issues of common chelonians, as well as
      recognizing illness, capture and restraint, sample collection, medication
      administration, and preventive care.

PMID- 15145400
TI  - Laboratory procedures.
AB  - The main foundation to veterinary medicine is the availability of laboratory
      tests. These tests may be performed in-clinic or at diagnostic laboratories. In
      clinic testing is advantageous in producing quick results, but demands sound
      technical ability, basic equipment,and access to some routine and special
      reagents. Laboratory-based testing can back up those routine techniques that
      mayor may not be available at the clinic level as well as provide specialized
      testing. The knowledge of commercially available diagnostic services is important
      as well as preparation and proper shipping of samples for accurate
      determinations.

PMID- 15145401
TI  - Exotic pet management for the technician.

PMID- 15145399
TI  - Invertebrate care.
AB  - Invertebrates are attracting increasing interest within the veterinary
      profession. They are also significant in their own right; as the Council of
      Europe's "Charter on Invertebrates" points out, they are the most important
      component of wild fauna as well as providing food, contributing to agriculture
      and forestry, and aiding medicine,industry, and crafts. Whenever invertebrates
      are kept in captivity they should be subject to high standards of management and
      care and veterinary attention-whether by the veterinarian or by the veterinary
      technician-should be based on sound biological and humanitarian principles.

PMID- 15145402
TI  - Eating and physical activity during adolescence: does it make a difference in
      adult health status?

PMID- 15145403
TI  - The impact of cognitive distortions, stress, and adherence on metabolic control
      in youths with type 1 diabetes.
AB  - PURPOSE: To investigate the role of cognitive distortions in the relationship
      between adherence behavior, diabetes-specific stress, general stress, and
      metabolic control. METHODS: Obtained questionnaire data, glucometer readings, and
      glycosylated hemoglobin (HbgA(1c)) assays from 143 youths (11-18 years old) with
      type 1 diabetes. Examined path model of relationships between cognitive
      distortions, stress, adherence behavior, and metabolic control. Data were
      analyzed using path analysis. RESULTS: Higher levels of negative cognitive
      distortions were associated with more stress (both diabetes-specific and
      general). Higher levels of general stress then led to less adherent behavior and
      subsequently poorer metabolic control (higher HbgA(1c)). More diabetes-specific
      stress also led to poorer metabolic control, as well as general stress.
      CONCLUSIONS: The findings indicate an indirect role of negative cognitive
      distortions in metabolic control. The current findings suggest that instead of
      the proposed direct link between cognitive distortions and adherence behavior, an
      indirect relationship may exist through stress.

PMID- 15145404
TI  - Injunctive social norms of adults regarding teen dating violence.
AB  - PURPOSE: To assess applied injunctive social norms of adults regarding teen
      dating violence (TDV) and compare them with those regarding adult domestic
      violence (ADV). METHODS: A total of 3679 California adults from six ethnic groups
      (roughly equal numbers of African-American, Hispanic, Korean-American, Vietnamese
      American, other Asian-American, and white respondents) participated in a 27
      minute interview. An experimental vignette design was used to test for
      associations among contextual (i.e., victim, assailant, and situational)
      characteristics of TDV and ADV, respondent demographic characteristics, and
      injunctive social norms (i.e., whether adults thought the behavior was wrong,
      illegal, or should be illegal, police should be called, or a restraining order
      issued). Data were analyzed using multivariate logistic regression, controlling
      for vignette variables (i.e., contextual characteristics) and respondent
      characteristics. Interactions were examined to test for differences in responses
      to TDV and ADV. RESULTS: Nearly all adults report that most forms of TDV are
      wrong (97%) and should be illegal (81%), and a majority support interventions for
      TDV such as calling police and issuing a restraining order. TDV involving sexual
      assault, physical assault, or weapons received the greatest levels of support for
      societal intervention. Differences in respondent judgments regarding TDV and ADV
      were evident when the victim had been raped. Respondent characteristics generally
      were not associated with responses. CONCLUSIONS: Findings suggest that there is
      general public support for prevention and intervention strategies aimed at
      reducing and responding to TDV, and may inform efforts to alter social norms and
      expectations regarding TDV.

PMID- 15145405
TI  - Correlates and predictors of violent behavior among adolescent drinkers.
AB  - PURPOSE: To examine a wide range of demographic characteristics and psychosocial
      factors to determine the cross-sectional correlates of violence and longitudinal
      predictors of violent initiation among adolescent drinkers. METHODS: We conducted
      secondary analyses of the 1995 (Time 1) and 1996 (Time 2) in-home surveys of the
      National Longitudinal Study of Adolescent Health (Add Health). This study
      included a nationally representative school-based sample (N=18,924) of
      adolescents in grades 7-12. The analyses were restricted to adolescent drinkers
      (n = 8885). Two logistic regression models were constructed using a backward
      elimination procedure to identify statistically significant cross-sectional
      correlates of violence and prospective predictors of violence initiation.
      RESULTS: Half (49%) of all adolescent drinkers reported violent behavior at Time
      1 and 15% of those who were not violent at Time 1 reported initiating violent
      behavior at Time 2. A total of 14 significant cross-sectional correlates of
      violence were identified that included measures of alcohol use, drug use and
      selling, exposure to drugs, delinquency, and poor school functioning. Four
      variables (high-volume drinking, illicit drug use, low grade point average, and
      having been suspended and/or expelled from school) were significant longitudinal
      predictors of the initiation of violent behavior. CONCLUSIONS: The factors
      significantly associated with violence pertain mostly to alcohol use, drug use
      and selling, exposure to drugs, delinquency, and poor school functioning.
      However, most of these problems and behaviors tend to occur in closer temporal
      proximity to violent behavior (i.e., within a year) and do not seem to
      developmentally precede initiation in violent behavior.

PMID- 15145406
TI  - Surveillance of drug use among American Indian adolescents: patterns over 25
      years.
AB  - PURPOSE: To examine the trends in drug use among American Indian adolescents
      attending schools on, or near, Indian reservations in the United States, to
      provide comparisons with non-Indian youth, and to discuss implications for
      prevention. METHODS: Reliable and valid school administered drug use surveys have
      been given every year for 25 years (1975-2000) to representative samples of
      Indian youth living on reservations, yielding a continuous record of trends in
      drug use. Comparisons are made with non-Indian youth with data from the
      Monitoring the Future project. Data were analyzed to obtain measures of lifetime
      prevalence ("ever tried a drug"), use in the last 30 days, and proportions at
      high risk and at moderate risk from their drug use. Comparisons utilized
      difference in proportion tests. RESULTS: From 1975 to 2000, reservation Indian
      youth show elevated levels of drug use for most illicit drugs compared with non
      Indian youth. Despite higher levels of use, the trends showing increases and
      decreases in use over time mirror those shown by non-Indian youth. Indian youth
      who use drugs can be divided into moderate and high levels of use. The number of
      youth in the moderate category varies over time whereas the number in the high
      category remains relatively constant. CONCLUSIONS: There is a clear need for
      intensive efforts to reduce the levels of drug use among Indian youth. Although
      interventions must be tailored to the social and cultural milieu of Indian
      reservations, the rates of use vary over time in the same pattern as seen for non
      Indian youth. Further, interventions must address the differing characteristics
      of high and moderate risk users of drugs.

PMID- 15145407
TI  - Low perceived chances for success in life and binge drinking among inner-city
      minority youth.
AB  - PURPOSE: To examine the relationship between low perceived chances for success in
      life and binge drinking in a sample of economically disadvantaged, predominantly
      minority, urban adolescents. METHODS: A sample of predominantly black and
      Hispanic students (N = 774) from 13 inner-city schools completed confidential
      questionnaires in the 7th, 8th, and 9th grades. Eight items measured students'
      estimation of achieving certain adaptive life goals. Students who reported that
      they typically drink five or more drinks per drinking occasion were identified as
      binge drinkers. RESULTS: Chi-square proportional analyses indicated that rates of
      binge drinking increased and perceived life chances decreased for both boys and
      girls from the 7th to 9th grade. A cross-lagged path analytic model revealed that
      higher perceived life chances in the 7th grade predicted less binge drinking in
      the 8th grade, whereas binge drinking in the 8th grade predicted lower perceived
      life chances in the 9th grade, controlling for change over time in both
      variables. CONCLUSIONS: Low perceived chances of success in life appear to play a
      role in the initiation and escalation of binge drinking during early adolescence,
      with a reciprocal relationship between the two factors developing over time.

PMID- 15145408
TI  - A look at nutritional supplement use in adolescents.
AB  - PURPOSE: To examine the use of nutritional supplements by adolescents.
      Supplements examined were those purported to influence performance and body mass.
      METHODS: 333 adolescents (190 male, 139 female, 4 nonrespondents) between the
      ages of 13 and 19 years, from a midwestern province in Canada, completed a pencil
      and-paper survey. Participants, who were enrolled in health and wellness/physical
      education classes, were requested to provide information about current and
      potential use of 10 readily available nutritional supplements, as well as their
      knowledge of these products as potentially performance enhancing. Differences in
      use, potential use, and knowledge, as a function of gender, age, and level of
      physical activity were examined using Chi-square analyses and ANOVA techniques.
      RESULTS: The most popular dietary aids were multivitamin/mineral preparations
      (42.5%). More adolescent males than females reported that they currently used
      both creatine and diuretics. Female respondents indicated that they would consume
      herbal weight control products significantly more than males. Older students and
      students reporting high levels of physical activity were significantly more
      likely to be supplementing with creatine and protein. Males were more likely than
      females to believe that creatine and androsterone were performance-enhancing
      agents. Individuals highly involved in physical activity tended to believe that
      multivitamins, creatine, L-carnitine, energizers, and protein supplements could
      enhance their performance. CONCLUSIONS: This study highlights the fact that many
      nutritional supplements fall within the spectrum of adolescent use, and that this
      use may be driven by misguided beliefs in their performance-enhancing abilities.
      Groups at particular risk, such as individuals involved in physical activity to a
      high degree, are highlighted and the need for gender-specific information is
      suggested.

PMID- 15145409
TI  - Chronic functional constipation in adolescents: clinical findings and motility
      studies.
AB  - OBJECTIVE: To evaluate the clinical findings and colonic transit time in
      adolescents with chronic functional constipation. METHODS: Forty-eight
      consecutive adolescents with chronic functional constipation referred to the
      Gastroenterology Service at the Hospital de Clinicas de Porto Alegre, Brazil were
      studied. Clinical parameters were assessed using a questionnaire. Total and
      segmental colonic transit time were measured with radiopaque markers. RESULTS:
      Mean age at first visit was 14 +/- 2 years, and age at onset of constipation was
      6 +/- 4 years; 90% of patients depended on laxatives, and 86% on intermittent
      enemas; 76% had a family history of constipation. There was no statistical
      difference in the amount of daily fiber ingested by patients and controls.
      Measurements of colonic transit time revealed that 60% of patients had slow
      transit constipation, 13% had pelvic floor dysfunction, 10% had slow transit
      constipation associated with pelvic floor dysfunction, and 17% had a normal
      colonic transit time. Decreased frequency of evacuation and palpable abdominal
      fecal mass were significantly associated with slow transit constipation.
      CONCLUSIONS: Functional constipation in adolescence consists of a heterogeneous
      group of colonic functional disorders. The identification of these different
      functional disorders in adolescents will guide specific treatment, which may
      prevent the progression of this symptom into adult life.

PMID- 15145410
TI  - Korean adolescents' exercise behavior and its relationship with psychological
      variables based on stages of change model.
AB  - PURPOSE: To examine the exercise behavior of Korean adolescents, reveal the
      differences in self-efficacy and decision balance by the stages of exercise
      behavior, and identify the relationship between exercise behavior and
      psychological variables. METHODS: A total of 671 adolescents randomly selected
      from junior high and high schools in Seoul were surveyed. Three Korean-version
      questionnaires were used to identify the stage of exercise behavior and
      psychological attributes of adolescents: Stage of Exercise Behavior Change
      Questionnaire, Decision Balance Scale for Exercise, and Exercise Self-efficacy
      Scale. Data were analyzed by frequency analysis, chi(2) test, MANOVA, correlation
      analysis, and regression analysis. RESULTS: The exercise pattern of Korean
      adolescents was different by each stage of exercise behavior: precontemplation
      (17.5%), contemplation (16.6%), preparation (20.4%), action (28.3%), and
      maintenance (17.2%). Significant differences in exercise behavior distribution
      emerged as a function of gender and age. In addition, exercise efficacy, exercise
      benefits and exercise barriers differentiated across the stages of exercise
      behavior. Furthermore, the findings revealed that adolescents' exercise behavior
      was significantly correlated with the selected psychological variables, and that
      psychological variables had a statistically significant impact on the exercise
      behavior. CONCLUSION: This study provides information about relatively unstudied
      Korean adolescents and has the potential to influence the development of better
      exercise interventions and health promotion programs for adolescents.

PMID- 15145411
TI  - Pilot study of abuse of asthma inhalers by middle and high school students.
AB  - During a school-based survey, middle and high school students (n = 1536) reported
      on their nonprescribed, lifetime use of asthma inhalers. Approximately 15% of 8th
      and 9th graders reported using nonprescribed asthma inhalers; the odds for this
      behavior were significantly higher for these students (2.25 and 2.30,
      respectively) and the nonprescribed use of asthma inhalers was significantly
      associated with higher rates of other drug use.

PMID- 15145412
TI  - Perioperative headaches in an adolescent: a most complex situation.

PMID- 15145413
TI  - In vivo and in vitro analysis of the resistance against viral haemorrhagic
      septicaemia virus in Japanese flounder (Paralichthys olivaceus) precedingly
      infected with aquabirnavirus.
AB  - The resistance of Japanese flounder (Paralichthys olivaceus Temminck et Schlegel)
      against a viral haemorrhagic septicaemia virus (VHSV) challenge induced by a
      preceding non-lethal aquabirnavirus (ABV) challenge was investigated through
      experimental dual-infections with different intervals between the two challenges.
      The non-specific protection conferred by the primary ABV infection against the
      secondary VHSV infection commenced at Day 3 and persisted up to Day 14 but
      vanished at Day 21 post-ABV challenge. The in vitro assay using HINAE (hirame
      natural embryo) cells demonstrated anti-VHSV activity in the serum of ABV
      challenged flounder from Day 1 to Day 14 but not at Day 21 post-ABV challenge. A
      high expression of a Mx gene, a molecular marker of type I interferon(s) (IFN)
      occurred in the head kidneys of ABV-challenged flounder from Day 1 to Day 7.
      These results suggest that the non-specific protection against the secondary VHSV
      infection in flounder was due to IFN(s) induced by the primary ABV infection.

PMID- 15145414
TI  - Molecular cloning and characterisation of a cell adhesion molecule, peroxinectin
      from the white shrimp Litopenaeus vannamei.
AB  - Expression of peroxinectin cDNA was obtained from haemocytes of white shrimp
      Litopenaeus vannamei using oligonucleotide primers based on the peroxinectin
      sequence of tiger shrimp Penaeus monodon and freshwater crayfish Pacifastacus
      leniusculus. The peroxinectin of L. vannamei was constitutively expressed. The
      cloning of peroxinectin cDNA fragment was subjected to RT-PCR using degenerated
      primers. Both 3'- and 5'-regions were isolated by rapid amplification of cDNA end
      RACE method. Analysis of nucleotide sequence revealed that the cDNA clone has an
      open reading frame of 2415 bp encoding a protein of 805 amino acids including a
      20 amino acid signal peptide. The calculated molecular mass of the mature protein
      (758 amino acids) is 89.1 kDa with an estimated pI of 7.5. Two putative integrin
      binding motifs, RGD (Arg-Gly-Asp) and KGD (Lys-Gly-Asp) were observed in L.
      vannamei peroxinectin. Sequence comparison showed that nucleotide homology has an
      overall similarity of 91% and 60% to that of P. monodon and P. leniusculus,
      respectively. Sequence comparison showed that peroxinectin deduced amino acid of
      L. vannamei has an overall similarity of 92% and 60% to that of P. monodon and P.
      leniusculus, respectively. The 432 bp fragment (partial cDNA) and 1016 bp
      fragment (genomic DNA) were obtained using specific primers PE2F and PE2R. There
      were three introns in the 1016 bp (genomic DNA) fragment. Peroxinectin transcript
      was significantly reduced when the shrimp was transferred to high temperature (34
      degrees C) as compared to the shrimp transferred to 18 degrees C and the control
      shrimp (26 degrees C). However, peroxinectin transcript did not change in 24 h
      post zymosan injection.

PMID- 15145415
TI  - Effects of the histiophagous ciliate Philasterides dicentrarchi on turbot
      phagocyte responses.
AB  - Philasterides dicentrarchi is an opportunistic histiophagous ciliate parasite
      causing systemic scuticociliatosis in cultured turbot (Scophthalmus maximus L.).
      This study investigated the effects of inoculation with live or killed
      trophozoites of this ciliate (plus 3% thioglycollate) on the in vitro phagocytic
      activity and respiratory-burst responses of inflammatory peritoneal leucocytes
      obtained from the fish thus treated. The phagocytic activity of leucocytes from
      fish inoculated with killed P. dicentrarchi was higher in the presence than in
      the absence of infected turbot serum (ITS). The effect of ITS was smaller in fish
      inoculated with live P. dicentrarchi, indicating modulation of the opsonic
      activity of ITS. Inoculation with live ciliates led to a significant increase in
      subsequent in vitro extracellular ROS production, but only when normal turbot
      serum (NTS) or ITS was included in the assay medium. Inclusion of live P.
      dicentrarchi in the medium abolished this increase, suggesting ROS-scavenging
      activity. Inoculation with live P. dicentrarchi led to a significant decline in
      subsequent in vitro intracellular ROS production; when NTS was included in the
      medium, there was a significant increase in intracellular ROS production, but no
      such increase was observed when ITS was included in the medium. Inoculation with
      live P. dicentrarchi alone did not increase subsequent in vitro NO? production in
      response to LPS; a significant increase was observed when NTS or ITS was included
      in the assay medium, but this increase was not affected by prior inoculation with
      P. dicentrarchi. These results suggest that the amphizoic nature of this parasite
      may reflect the ease with which it can develop mechanisms of evasion of the host
      immune response.

PMID- 15145416
TI  - The immune stimulatory effect of sodium alginate on the white shrimp Litopenaeus
      vannamei and its resistance against Vibrio alginolyticus.
AB  - The total haemocyte count (THC), differential haemocyte count (DHC),
      phenoloxidase activity, respiratory burst (release of superoxide anion),
      superoxide dismutase activity, phagocytic activity and clearance efficiency to
      the pathogen Vibrio alginolyticus were measured when the white shrimp Litopenaeus
      vannamei (9.4-11.3 g) were injected individually with sodium alginate at 10, 20
      or 50 microg g(-1). No significant differences in THC, DHC and superoxide
      dismutase activity were observed among the shrimp injected with saline and those
      injected with sodium alginate at 10, 20 or 50 microg g(-1). However, L. vannamei
      injected with sodium alginate at 20 microg g(-1)increased its phenoloxidase
      activity and respiratory burst after 2 days and one day, respectively. L.
      vannamei injected with sodium alginate at 50 microg g(-1)maintained a higher
      phagocytic activity and clearance efficiency to V. alginolyticus after 4 days. In
      another experiment, L. vannamei which had been injected with sodium alginate,
      were challenged with V. alginolyticus at 2x10(5)colony-forming units (CFU)
      shrimp(-1)and then placed in seawater of 34 per thousand. The survival of shrimp
      that received sodium alginate at either dose was significantly higher than that
      of control shrimp at the termination of the experiment (6 days after the
      challenge). It is therefore concluded that L. vannamei received sodium alginate
      at 10 microg g(-1)or more and increased its immune ability and resistance from V.
      alginolyticus infection.

PMID- 15145417
TI  - Degranulation of eosinophilic granule cells in neurofibromas and gastrointestinal
      tract in the bicolor damselfish.
AB  - Damselfish neurofibromatosis (DNF) is a neoplastic disease affecting bicolor
      damselfish (Stegastes partitus Poey) on Florida reefs. Previous studies have
      demonstrated high densities of eosinophilic granule containing cells (EGC), the
      proposed equivalent of mast cells in fishes, in neurofibromas and malignant
      peripheral nerve sheath tumors (mpnst) in DNF. These lesions are similar to those
      in the disease neurofibromatosis type 1 (NF1) in humans, which contain large
      numbers of mast cells. In the present study, experiments were conducted to
      measure the response of EGC in these tumors as well as in the submucosa of the
      digestive tract to the mast cell degranulating agent compound 48/80.
      Degranulation of these cells was visible by light microscopy and characterized by
      conspicuous swelling of granules and often by the presence of free granules
      adjacent to the EGC. Degranulation occurred by release of intact granules
      (diacytosis), as reported in other fishes, rather than by fusion of granules with
      the cell membrane (exocytosis) as reported in mast cells in mammals. Baseline
      levels of EGC exhibiting degranulation ranged from 20-26% in the submucosa to 30%
      in tumors. Within 1-2h of exposure to compound 48/80, significant increases in
      average levels of degranulation were observed, to 67% in the gut and 72% in
      tumors. Degranulation was significantly more extensive in the tumors than in the
      gut. The outermost edges of the tumors contained significantly higher densities
      of EGC but these cells exhibited lower rates of degranulation than those in the
      inner regions of tumors. These observations support the hypothesis that the EGC
      present in neurofibromas and mpnst in DNF are equivalent to the mast cell
      component in neurofibromas in NF1.

PMID- 15145418
TI  - In vitro cytotoxicity of crustacean immunostimulants for lobster (Homarus
      gammarus) granulocytes demonstrated using the neutral red uptake assay.
AB  - The neutral red uptake (NRU) cell viability assay was adapted for use with
      lobster Homarus gammarus (Linnaeus, 1758) granulocytes cultured in vitro. The
      assay was more sensitive than the conventional trypan blue exclusion assay and
      facilitated a higher sample throughput than subjective microscope-based
      assessments of cell viability. The NRU assay was demonstrated to have a linear
      response from 470 to at least 126000 cells cm(-2). It was used to investigate the
      acute cytotoxicity of three commercial and two candidate crustacean aquaculture
      immunostimulants on lobster granulocytes. All five stimulants had a cytotoxic
      action on the granulocytes and the toxic dose for some of these stimulants was
      found to be below their commercially prescribed dose. The long term energetic
      cost of the use of these stimulants and the concomitant potential for a reduction
      in growth rate of cultured decapod crustaceans, which is fundamental to the
      success of commercial aquaculture, is identified and discussed.

PMID- 15145420
TI  - Presence of multiple isoforms of TNF alpha in carp (Cyprinus carpio L.): genomic
      and expression analysis.

PMID- 15145419
TI  - Expression of pro-inflammatory cytokines in rainbow trout (Oncorhynchus mykiss)
      during an infection with Ichthyophthirius multifiliis.
AB  - Inflammatory processes are known to take place in the skin of fish during an
      infection with the parasitic ciliate Ichthyophthirius multifiliis. The present
      study shows that the pro-inflammatory cytokines interleukin 1 beta (IL-1beta) and
      tumor necrosis factor alpha (TNF-alpha), the chemokine interleukin 8 (IL-8) and
      the type II IL-1 receptor (IL-1RII) are expressed in rainbow trout during an
      infection. In the skin an up to 17.8 times increase in the expression level of IL
      1beta relative to uninfected controls was seen 4 days after infection.
      Upregulated expression of IL-1beta was likewise observed in the head kidney and
      spleen during the infection although to a lesser degree. TNF-alpha expression was
      seen in all examined tissues, with an increase in transcript level in the skin of
      up to 3.2 times the level in uninfected fish. A significant increase in the
      expression of IL-8 was evident in the skin and also to a lower extent in the head
      kidney and spleen. Expression of the down regulatory IL-1RII was seen in all
      three tissues. The potential involvement of the expression of these genes and
      their relevance in an infection with I. multifiliis are discussed.

PMID- 15145421
TI  - Shoulder anatomy and biomechanics.
AB  - The evaluation of shoulder disorders is challenging because of anatomic and
      biomechanical complexities. The shoulder comprises three synovial joints and two
      movement interfaces. The following principles are important to establish an
      accurate anatomic diagnosis and to develop a treatment plan: (1) perform a
      careful history and physical examination; (2) determine whether or not the
      problem is mechanical; (3) for mechanical problems, establish pathophysiologic
      and mechanical diagnoses; and (4) use mechanical impairments as the basis for
      therapeutic interventions.

PMID- 15145422
TI  - Clinical evaluation of the shoulder.
AB  - Shoulder pain is an exceptionally common problem in physiatric practice.
      Evaluation and management of patients with shoulder dysfunction can challenge
      even the most experienced practitioner. The complexity and inherent instability
      of the shoulder lead to functional overload of various bony and soft tissues
      within the joint complex and adjacent structures.Additionally, shoulder pain may
      be the initial manifestation of a potentially serious condition. Consequently, a
      detailed and systematic approach to the evaluation of a patient with shoulder
      pain is crucial in establishing a complete and accurate diagnosis. A skillfully
      performed history and physical examination allows identification of specific
      tissue pain generators and biomechanical dysfunction throughout the kinetic
      chain. Only after these elements have been defined clearly can an appropriate
      rehabilitation program be de-signed. A thorough clinical assessment also can aid
      in the detection of serious diseases that masquerade as shoulder pain. An
      effective clinical evaluation enhances the quality and cost-effectiveness of care
      and facilitates a successful outcome in most cases.

PMID- 15145423
TI  - Radiologic evaluation of the shoulder girdle.
AB  - The radiologic evaluation of the shoulder girdle is an important adjunct to the
      clinical history and physical examination. Close collaboration between
      musculoskeletal clinicians and musculoskeletal radiologists improves the
      diagnostic performance of imaging studies. Technologic advantages, especially in
      MRI, have improved appreciation of shoulder anatomy, biomechanics, and injury
      patterns, allowing for the development of more targeted surgical and nonsurgical
      treatment strategies. This article reviews imaging considerations of the major
      clinical entities related to the shoulder.

PMID- 15145424
TI  - Shoulder injections for osteoarthritis and other disorders.
AB  - Shoulder injection procedures are powerful diagnostic and therapeutic tools for
      the care of patients with osteoarthritis and other pathologic conditions of the
      shoulder-girdle region. Although questions regarding many of the details of the
      specific procedures still need to be answered, a modest body of literature is
      available. The musculoskeletal physiatrist is in a good position to contribute to
      this knowledge base through further clinical research.

PMID- 15145425
TI  - Glenohumeral arthritis and its management.
AB  - Glenohumeral arthritis has many different etiologies, including osteo-arthritis,
      secondary degenerative joint disease, rheumatoid arthritis,avascular necrosis,
      cuff tear arthropathy, and capsulorrhaphy arthropathy. Each of these diagnoses
      may have different underlying pathoanatomy and pathomechanics. The treating
      physician must recognize how these characteristics impair shoulder function so
      that the prescribed course of treatment addresses the root causes of shoulder
      dysfunction. The patient's age. level of physical activity, and comorbidities
      should be taken into account, and the intended management should be weighed
      against how these factors may interfere with treatment efficacy over the long
      term. The goal of treatment is to restore comfort, motion, strength, and
      stability to the shoulder in a safe and reliable manner. Conservative treatments
      should aim to optimize shoulder flexibility, maintain muscle function, and reduce
      inflammation. Activity modification is crucial but often unreasonable to the
      active patient. Temporary surgical approaches include arthroscopic debridement
      and synovectomy. These approaches may be appropriate for a younger patient with
      some remaining joint space and a functional rotator cuff. Definitive surgical
      treatment typically involves either a proximal humerus replace mentor a total
      shoulder replacement. The decision to resurface the glenoid should be based on
      the patient's age, diagnosis, available bone stock, and physical demands. The
      surgeon must be familiar with the options provided by the given implant system so
      that the proper balance of motion and stability can be restored with a close
      approximation of the native anatomy. Inexperienced hands, good-to-excellent
      results can be achieved in greater than 90% of properly selected patients.
      Glenoid component failure is one of the most common complications of shoulder
      arthroplasty, highlighting the need to select carefully patients in whom glenoid
      resurfacing is warranted.

PMID- 15145426
TI  - Rotator cuff disease.
AB  - Rotator cuff disease is a complex condition. It includes a variety of
      pathologies, ranging from tendinosis to complete tear. The cause seems to be
      multifactorial and is most likely a combination of major trauma, microtrauma from
      daily wear and tear, and age related degeneration. When establishing a program
      for the patient with rotator cuff dysfunction, the rehabilitation specialist
      should consider biomechanical factors, the patient's functional goals, and issues
      beyond the shoulder that may affect the course of the disease.

PMID- 15145427
TI  - Shoulder impingement syndrome.
AB  - Shoulder rotator cuff impingement syndrome is treatable-nonoperatively or
      operatively if prompt diagnosis and treatment are undertaken.Proper evaluation
      includes a good history, physical examination, and appropriate diagnostic
      testing. The main goal in treatment is to return patients to their previous
      activity level, and the prognosis usually is good.Treatment usually is successful
      with nonoperative means, but if necessary operative intervention is successful
      with correct patient selection.

PMID- 15145428
TI  - Disorders of the long head of the biceps tendon.
AB  - The long head of the biceps tendon long has been suspected as a source of
      clinically significant pathology and symptoms. It has only been more recently,
      however, that medical science has been able to delineate and describe in detail
      important anatomic structures and relationships of structures, functions, and
      pathophysiologic mechanisms related to the tendon. The function of the tendon has
      been disputed, but evidence now suggests that it does play a role in
      stabilization of the glenohumeral joint. This function should be considered when
      planning a rehabilitation program for the shoulder. Terminology used to describe
      disorders of the long head of the biceps tendon has been confusing at times, but
      with the use of appropriate terminology, an improved dialogue can exist between
      clinicians and other practitioners. Although conservative treatment generally is
      recommended and often is sufficient in obtaining an acceptable outcome, surgical
      treatment after failed conservative care or in the setting of an associated
      rotator cuff or labral lesion may be appropriate.

PMID- 15145432
TI  - Use of isotopic gamma sources for identifying anti-personnel landmines.
AB  - Density is one of the indicators that can be utilized to distinguish an explosive
      material from an innocuous anomaly. Compton scattering of photons can be used to
      provide such density indication. Although X-rays have been employed for this
      purpose, isotopic gamma-rays offer some advantage for use in a portable device,
      because of their small size and self-powered nature. Radioisotopes were
      considered in the 1970's by the US Army. This work re-examines the utility of
      these sources for the detection of shallowly buried anti-personnel landmines.
      Monte Carlo studies indicated that the most effective configuration for
      identifying and locating a buried landmine should employ a collimated (241)Am
      source, along with a set of well-collimated detectors. Experimental measurements
      verified the feasibility of the proposed method and demonstrated the
      detectablility of mockups of landmines as small as 45 mm in diameter buried near
      the soil surface, or mockups larger than 80 mm in diameter buried at a depth of
      80 mm, in light soil. In heavy soil, targets 80 mm in diameter were detectable at
      a depth of 30 mm. The use of the low-energy (60 keV) (241)Am source makes it
      possible to design a light-weight hand-held device that can augment other methods
      of detecting plastic landmines.

PMID- 15145433
TI  - Investigations on landmine detection by neutron-based techniques.
AB  - Principles and techniques of some neutron-based methods used to identify the
      antipersonnel landmines (APMs) are discussed. New results have been achieved in
      the field of neutron reflection, transmission, scattering and reaction
      techniques. Some conclusions are as follows: The neutron hand-held detector is
      suitable for the observation of anomaly caused by a DLM2-like sample in different
      soils with a scanning speed of 1m(2)/1.5 min; the reflection cross section of
      thermal neutrons rendered the determination of equivalent thickness of different
      soil components possible; a simple method was developed for the determination of
      the thermal neutron flux perturbation factor needed for multi-elemental analysis
      of bulky samples; unfolded spectra of elastically backscattered neutrons using
      broad-spectrum sources render the identification of APMs possible; the knowledge
      of leakage spectra of different source neutrons is indispensable for the
      determination of the differential and integrated reaction rates and through it
      the dimension of the interrogated volume; the precise determination of the C/O
      atom fraction requires the investigations on the angular distribution of the
      6.13MeV gamma-ray emitted in the (16)O(n,n'gamma) reaction. These results, in
      addition to the identification of landmines, render the improvement of the non
      intrusive neutron methods possible.

PMID- 15145434
TI  - The status of the Delft University Neutron Backscatter Landmine Detector
      (DUNBLAD).
AB  - The neutron backscattering technique may be applied to search for non-metallic
      landmines in relatively dry soils. A detector system using this technique has
      been constructed. Tests showed that anti-tank mines can reliably be found, but
      that, depending on the circumstances, anti-personnel mines may escape detection.
      A first test with a pulsed neutron generator shows that further improvements can
      be achieved by applying a window on the neutron transit time.

PMID- 15145435
TI  - Detection of anti-personnel landmines by neutron scattering and attenuation.
AB  - Four methods for employing neutrons to detect abandoned small anti-personnel
      landmines are presented and discussed. The techniques used are based on
      measurements of effects due to the scattering of neutrons on the hydrogen content
      of the landmine.

PMID- 15145437
TI  - Detection of landmines by using 14 MeV neutron tagged beams.
AB  - A large-area scanning system using 14 MeV tagged neutrons has been built. The
      associated (4)He particles emitted in the D+T reaction are detected in an array
      of Parallel Plate Avalanche Counters that defines a scanning plane having about
      10 x 100 cm(2) area. Coincident gamma-rays are detected by 10 BaF(2)
      scintillators. The capability of the system to determine the presence and the
      position of samples and to perform an on-line background subtraction is
      demonstrated. Test with landmines are also reported. This technique allows a
      significant improvement of the signal-to-noise ratio searching for hidden threat
      materials. The use with portable sealed-tube generators is foreseen.

PMID- 15145438
TI  - Detection of buried explosives using portable neutron sources with nanosecond
      timing.
AB  - Significant reduction of time needed to identify hidden explosives and other
      hazardous materials by the "neutron in, gamma out" method has been achieved by
      introducing timed (nanosecond) neutron sources-the so-called nanosecond neutron
      analysis technique. Prototype mobile device for explosives' detection based on a
      timed (nanosecond) isotopic (252)Cf neutron source has been created. The
      prototype is capable of identifying 400 g of hidden explosives in 10 min. Tests
      have been also made with a prototype device using timed (nanosecond) neutron
      source based on a portable D-T neutron generator with built-in segmented detector
      of accompanying alpha-particles. The presently achieved intensity of the neutron
      generator is 5x10(7)n/s into 4pi, with over 10(6) of these neutrons being
      correlated with alpha-particles detected by the built-in alpha-particle detector.
      Results of measurements with an anti-personnel landmine imitator are presented.

PMID- 15145436
TI  - Monte Carlo simulations to advance characterisation of landmines by pulsed
      fast/thermal neutron analysis.
AB  - The performance of a detection system based on the pulsed fast/thermal neutron
      analysis technique was assessed using Monte Carlo simulations. The aim was to
      develop and implement simulation methods, to support and advance the data
      analysis techniques of the characteristic gamma-ray spectra, potentially leading
      to elemental characterisation of innocuous objects using the full spectrum
      analysis (FSA) approach. The simulations were carried out with a simplified tool,
      based on a 14MeV DT pulse-neutron source and a bismuth-germanate detector. A MCNP
      based method for de-coupling the radiation transport in mixed (n,gamma) fields,
      to generate separate sets of standard detector gamma-ray responses for individual
      elements, is outlined. When normalised and experimentally benchmarked in terms of
      the pulse-neutron source production rate, the standard spectra can be
      incorporated into algorithms for the FSA of in situ measurements and elemental
      fingerprinting of the inspected object.

PMID- 15145440
TI  - Feasibility study for a low-cost 3D gamma-ray camera.
AB  - A novel gamma-ray camera is proposed based on Positron Annihilation Compton
      Scattering Imaging (PACSI). The camera comprises a positron source and a fast,
      position-sensitive gamma-ray detector. Monte Carlo simulations of the camera have
      demonstrated that it should be capable of forming 3-D images of objects that can
      only be viewed from one side. A simple 1-D PACSI camera has been constructed and
      tested in the laboratory. Prospects for the construction of a full 3-D prototype
      camera are discussed.

PMID- 15145439
TI  - Development of a thermal neutron sensor for Humanitarian Demining.
AB  - A thermal neutron sensor prototype for Humanitarian Demining has been developed,
      trying to minimize cost and complexity of the system as required in such
      application. A (252)Cf source or a sealed-tube neutron generator is employed to
      produce primary fast neutrons that are thermalized in a moderator designed to
      optimize the neutron capture reaction yield in buried samples. A description of
      the sensor, including the performances of the acquisition system based on a Flash
      ADC card and final tests with explosive simulants are reported. A comparison of
      the sensor performance when using a radioactive source to that when employing a
      sealed-tube neutron generator is presented. Limitations and possible applications
      of this technique are discussed.

PMID- 15145441
TI  - Chemical composition identification using fast neutrons.
AB  - Measurements of characteristic gamma ray spectra resulting from A(n, n'gamma)A
      reactions induced by 14 eV neutrons on different bulk samples (graphite, water,
      melamin) were performed. Of particular importance are results of experiments with
      objects buried in the soil. It has been shown that samples of graphite can be
      identified when buried under 10 m of soil. NaI(Tl) and BaF(2) scintilators were
      used as gamma ray detectors. Background radiation was reduced by the associated
      alpha particle technique.

PMID- 15145442
TI  - Nongenomic effects of 17beta-estradiol--diversity of membrane binding sites.
AB  - The classical model of the action of 17beta-estradiol comprises binding of this
      gonadal steroid hormone to nuclear estrogen receptors leading to the modulation
      of gene transcription and protein synthesis. However, in the last few years
      several evidences about the rapid nongenomic action of 17beta-estradiol via the
      stimulation of putative receptors located in the cell membrane have also been
      reported. These nongenomic responses occur within a few minutes and are
      insensitive to the inhibitors of transcription and translation; however, no such
      membrane receptors have been cloned so far. In this review article, we present a
      survey showing that such membrane binding sites of 17beta-estradiol have rather
      different ligand specificity properties than that of classical genomic estrogen
      receptors concerning the potential activity of different estrogens and other
      steroid hormones, supporting the conception of structurally distinct receptors
      for genomic and nongenomic pathways. The fact that rapid responses to 17beta
      estradiol could be induced by a wide concentration range from some picomolar to
      high micromolar doses points to the diversity of these nongenomic membrane
      binding sites as well as the complexity of their functioning.

PMID- 15145443
TI  - The treatment of glucocorticoid-induced osteoporosis.
AB  - Glucocorticoid use results in an increase risk for fractures. Over the past 10
      years, we have a greater understanding of the epidemiology, pathophysiology,
      prevention and treatment of glucocorticoid induced osteoporosis. This article
      reviews these recent findings and selective practice guidelines.

PMID- 15145444
TI  - Identification of novel estrogen receptor alpha antagonists.
AB  - We have identified novel estrogen receptor alpha (ERalpha) antagonists using both
      cell-based and computer-based virtual screening strategies. A mammalian two
      hybrid screen was used to select compounds that disrupt the interaction between
      the ERalpha ligand binding domain (LBD) and the coactivator SRC-3. A virtual
      screen was designed to select compounds that fit onto the LxxLL peptide-binding
      surface of the receptor, based on the X-ray crystal structure of the ERalpha LBD
      complexed with a LxxLL peptide. All selected compounds effectively inhibited 17
      beta-estradiol induced coactivator recruitment with potency ranging from nano
      molar to micromolar. However, in contrast to classical ER antagonists, these
      novel inhibitors poorly displace estradiol in the ER-ligand competition assay.
      Nuclear magnetic resonance (NMR) suggested direct binding of these compounds to
      the receptors pre-complexed with estradiol and further demonstrated that no
      estradiol displacement occurred. Partial proteolytic enzyme digestion revealed
      that, when compared with 17-beta-estradiol- and 4 hydroxy-tamoxifen (4-OHT) bound
      receptors, at least one of these compounds might induce a unique receptor
      conformation. These small molecules may represent new classes of ER antagonists,
      and may have the potential to provide an alternative for the current anti
      estrogen therapy.

PMID- 15145445
TI  - Impaired nuclear localization of vitamin D receptor in leukemia cells resistant
      to calcitriol-induced differentiation.
AB  - Calcitriol, the hormonal form of vitamin D(3), induces differentiation of
      monocytic leukemia cell lines in vitro, without inducing cytotoxicity of the
      cells. Besides this broad in vitro activity, a clinical implementation of
      calcitriol, or its analogs, as agents for differentiation therapy has been
      unsuccessful until now. A better understanding of cellular activities of
      calcitriol necessary for completion of cell differentiation program could help
      find better solutions for differentiation therapy of myeloid leukemias. In this
      paper we describe work carried on subline of acute monocytic leukemia, THP-1
      resistant to calcitriol induced differentiation. This resistance correlates with
      impaired nuclear localization of vitamin D receptor, but not with its total
      expression in the cells. It also correlates with the resistance to calcitriol
      induced growth inhibition, and to phorbol myristate acetate (PMA)-induced cell
      differentiation.

PMID- 15145446
TI  - Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA
      and glucocorticoid receptor protein during mouse embryonic development.
AB  - Accumulating evidence suggests that the actions of glucocorticoids in target
      tissues are critically determined by the expression of not only the
      glucocorticoid receptor (GR) but also the glucocorticoid-metabolizing enzymes,
      known as 11beta-hydroxysteroid dehydrogenase types 1 and 2 (11beta-HSD1 and
      11beta-HSD2). To gain insight into the role of glucocorticoids in fetal
      development, the expression patterns of the two distinct 11beta-HSD isozymes and
      GR were studied in the mouse embryo from embryonic day 12.5 (E12.5, term = E19)
      to postnatal day 0.5 (P0.5) by in situ hybridization and immunohistochemistry,
      respectively. 11beta-HSD1 mRNA was detected in the heart as early as E12.5 and
      maintained thereafter. In the lung and liver, 11beta-HSD1 mRNA was first detected
      between E14.5 and E16.5, increased to high levels towards term and maintained
      after birth. Relatively low levels of 11beta-HSD1 mRNA were also detected in the
      kidney, adrenal glands and gastrointestinal tract at E18.5. However, the mRNA for
      11beta-HSD1 was undetectable in all other embryonic tissues including the brain.
      In contrast, kidney was the only organ that expressed appreciable levels of
      11beta-HSD2 mRNA during embryonic life. The level of 11beta-HSD2 mRNA in the
      kidney increased dramatically in the newborn, which coincided with expression of
      11beta-HSD2 mRNA in the whisker follicle, tooth and salivary gland. Distinct from
      the profiles of 11beta-HSD1 and 11beta-HSD2 mRNA, GR protein was detectable in
      all tissues at all ages studied except for the thymus, salivary gland, and bone.
      Taken together, the present study demonstrates that tissue- and developmentally
      stage specific expression of 11beta-HSD1 and 11beta-HSD2 as well as GR occurs in
      the developing mouse embryo, thus highlighting the importance of these two
      enzymes and GR in regulating glucocorticoid-mediated maturational events in
      specific tissues during murine embryonic development.

PMID- 15145447
TI  - Estrogen-inducible uterine flavonoid binding sites: is it time to reconsider?
AB  - Epidemiological data support the beneficial effect of plant flavonoids on human
      health including anti-inflammatory and cancer preventing actions. The
      phytoestrogen flavonoids might interfere with estrogen action. The possible
      relations between the steroid- and the flavonoid-signalling in animal and plant
      cells have been addressed in numerous studies in the past decade. In search for
      possible sites of conjunction between these phenomena the post-receptor targets
      must not be disregarded. The estrogen-inducible type II estrogen binding sites of
      rat uteri have first been reported 25 years ago by Clark and coworkers [Biochem.
      Biophys. Res. Commun. 81 (1978) 1]. These sites are known to bind catecholic
      flavonoids with considerable affinity. Behaviour of the tyrosinase-like enzymatic
      activity associated with these sites appeared reminiscent to the recently
      described dopachrome oxidase or tautomerase activity exhibited by the cytokine
      macrophage migration inhibitory factor (MIF) inasmuch as it also accepts a broad
      range of catecholic melanogenic precursors. Therefore we assessed, whether the
      known type II ligand flavonoids interfere with the MIF tautomerase. We report
      here, that luteolin and quercetin have a biphasic effect on the enol-keto
      conversion of phenylpyruvate mediated by MIF tautomerase. We also demonstrate the
      presence of MIF immunoreactivity by Western blotting in rat uterine nuclear
      extracts prepared according to the method that yields high type II binding
      activity. These data support the possible participation of MIF in type II
      estrogen binding phenomena.

PMID- 15145448
TI  - Sulfation of tibolone and tibolone metabolites by expressed human cytosolic
      sulfotransferases.
AB  - Tibolone is an important therapeutic agent used in the treatment of menopausal
      symptoms in many countries and has beneficial effects on menopausal and
      postmenopausal vasomotor, bone, vaginal and mood symptoms without affecting the
      endometrial, breast or cardiovascular systems. The rapid metabolism of tibolone
      to active metabolites including 3alpha-OH-tibolone, 3beta-OH-tibolone and
      Delta(4)-tibolone may be important in its tissue-specific effects. Sulfation also
      has a major role in the metabolism and regulation of the tissue-specific activity
      of tibolone and its metabolites. The ability of seven major expressed human
      sulfotransferase (SULT) isoforms to sulfate tibolone and its three metabolites
      was examined. Expressed human SULT2A1 was capable of sulfating tibolone and all
      three metabolites with the highest affinity for 3alpha-OH-tibolone. SULT1E1
      conjugated both 3-OH-tibolone metabolites and tibolone itself slightly. SULT2B1b
      sulfated both 3-OH metabolites but not tibolone or Delta(4)-tibolone. SULT
      isoforms 1A1, 1A3, 1B1 and 1C1 did not demonstrate detectable activity. Sulfation
      of tibolone and its metabolites by human tissue cytosols was analyzed to
      determine whether the pattern of tibolone sulfation corresponded to the known
      expression of SULT isoforms in each tissue. The tissue-specific effects of
      tibolone may be regulated in part by the inactivation of tibolone and its
      metabolites by specific human SULT isoforms.

PMID- 15145449
TI  - 3alpha/beta,20beta-hydroxysteroid dehydrogenase (porcine testicular carbonyl
      reductase) also has a cysteine residue that is involved in binding of cofactor
      NADPH.
AB  - Besides residue of the catalytic triad that is conserved in the short-chain
      dehydrogenase/reductase (SDR) superfamily, a Cys side chain reportedly plays
      functional roles in NADP-dependent 15-hydroxyprostaglandin dehydrogenase and
      human carbonyl reductase (CR). The three-dimensional structure of porcine
      3alpha/beta,20beta-hydroxysteroid dehydrogenase, also known as porcine testicular
      carbonyl reductase, demonstrates the proximity of the Cys 226 side chain to the
      bound NADP. However, no clear explanation with respect to the basis of the
      catalytic function of the Cys residue is yet available. By chemical modification,
      point mutation, and kinetic analysis, we determine that two Cys residues, Cys 149
      and Cys 226, are involved in the enzyme activity. Furthermore, we found that
      pretreatment with NADP markedly protects the enzyme from inactivation by 4
      (hydroxyl mercury) benzoic acid (4-HMB), thereby confirming that Cys 226 is
      involved in binding of the cofactor. On the basis of the tertiary structure of
      3alpha/beta,20beta-HSD, the possible roles of Cys residues, especially that of
      Cys 226, in enzyme action and in the binding of cofactor NADPH are discussed.

PMID- 15145450
TI  - Serum steroid hormones, sex hormone-binding globulin concentrations, and urinary
      hydroxylated estrogen metabolites in post-menopausal women in relation to
      daidzein-metabolizing phenotypes.
AB  - Equol and O-desmethylangolensin (O-DMA) are products of bacterial metabolism of
      daidzein, an isoflavone in soybeans; thus, the presence or absence of equol
      and/or O-DMA in urine is a marker of particular intestinal bacteria profiles.
      Plasma hormone concentrations may be lower in pre-menopausal women who harbor the
      bacteria capable of producing equol (equol producers) compared to women who do
      not (equol non-producers). We evaluated concentrations of serum hormones, sex
      hormone-binding globulin (SHBG), and urinary 2-hydroxyestrone (2-OH E(1)) and
      16alpha-hydroxyestrone (16alpha-OH E(1)) in relation to equol-producer and O-DMA
      producer phenotypes in 89 post-menopausal women. Follicle stimulating hormone
      (FSH) was 23% greater in O-DMA-producers compared to non-producers (P = 0.04). No
      significant differences in serum estrogens, androgens, metabolic hormones, or
      SHBG were observed in relation to either daidzein-metabolizing phenotype.
      Compared with non-producers within each phenotype, age-adjusted 2-OH E(1):16alpha
      OH E(1) was 27% greater (P = 0.06) in equol-producers and 9% greater (P > 0.10)
      in O-DMA-producers, and 2-OH E(1) concentrations were 24% greater in equol
      producers (P = 0.07) and 42% greater in O-DMA producers (P = 0.02). No
      significant differences in 16alpha-OH E(1) were observed in relation to either
      phenotype. These results suggest that interindividual variability in intestinal
      bacteria may be related to differences in products of hormone metabolism in post
      menopausal women.

PMID- 15145451
TI  - 2-phenylindole sulfamates: inhibitors of steroid sulfatase with antiproliferative
      activity in MCF-7 breast cancer cells.
AB  - A number of 2-phenylindole sulfamates with lipophilic side chains in 1- or 5
      position of the indole were synthesized and evaluated as steroid sulfatase
      (estrone sulfatase) inhibitors. Most of the new sulfamates inhibited the
      enzymatic hydrolysis of estrone sulfate in MDA-MB 231 breast cancer cells with
      IC(50) values between 2 nM and 1 microM. A favorable position for a long side
      chain is the nitrogen of a carbamoyl group at C-5 of the indole when the phenyl
      ring carries the sulfamate function. These derivatives inhibit gene activation in
      estrogen receptor (ER)-positive MCF-7 breast cancer cells in submicromolar
      concentrations and reduce cell proliferation with IC(50) values of ca. 1 microM.
      All of the potent inhibitors were devoid of estrogenic activity and have the
      potential for in vivo application as steroid sulfatase inhibitors.

PMID- 15145452
TI  - Antibody bound to the surface antigen MPB83 of Mycobacterium bovis enhances
      survival against high dose and low dose challenge.
AB  - Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium
      bovis is a significant disease of man and animals. Whilst cellular immunity is
      the major immunological component required for protection against these
      organisms, recent reports have suggested that monoclonal antibodies can modify
      infection with M. tuberculosis. To test whether the same was true for M. bovis
      infection, we determined the effect of preincubation of M. bovis with a
      monoclonal antibody on subsequent intravenous infection of mice. Antibodies bound
      to the surface of M. bovis increased the survival time of mice infected with M.
      bovis and changed the morphology of granulomas and the distribution of acid-fast
      bacilli in the lung. These studies suggest that antibodies directed to the
      surface of virulent mycobacteria can modulate their virulence in vivo.

PMID- 15145453
TI  - Human salivary aggregation in Streptococcus intermedius type g strains:
      relationship with IgA.
AB  - Bacterial aggregation is an important step in elimination from the human body to
      protect against infection. Streptococcus intermedius K1K aggregates in human
      saliva. In this study, the salivary agglutinin was identified. The aggregation
      level was very strong in sonic-treated saliva and 1-microm filtrate.
      Preincubation of human saliva with anti-human alpha chain serum or anti-human
      whole saliva serum completely inhibited aggregation, but preincubation with anti
      human micro chain serum or anti-Fc fragment of human IgG serum had no effect.
      Agglutinin of human saliva that could aggregate the strain K1K was purified using
      DEAE-Sepharose CL-6B, Phenyl-Sepharose CL-4B and Sephacryl S200HR gel filtration.
      Purified salivary agglutinin was characterized with electrophoresis and
      immunological techniques, indicating that purified material was IgA. Bacterial
      aggregation was dependent on the presence of calcium. Saliva filtrate specimens
      from eight healthy men and eight women showed different aggregation activities.
      Three men and one woman had little activity. These data show that the present
      bacterial aggregation was an immunoreaction between IgA in saliva and the
      bacteria dependent on the levels of calcium. In addition, the IgA in human saliva
      related with possible calcium-dependent antigen(s) on the surface of strain K1K.

PMID- 15145454
TI  - Exploration of Moraxella catarrhalis outer membrane proteins, CD and UspA, as new
      carriers for lipooligosaccharide-based conjugates.
AB  - Moraxella catarrhalis outer membrane proteins, CD and ubiquitous surface protein
      A (UspA), were used as carriers for M. catarrhalis detoxified lipooligosaccharide
      (dLOS)-based conjugates. Our study was designed to investigate the feasibility of
      CD and UspA as protein carriers for dLOS-based conjugates and their possible
      synergic effects on protection from both anti-LOS and anti-CD or anti-UspA
      antibody responses. Female Balb/c mice were immunized subcutaneously three times
      with dLOS-CD or dLOS-UspA conjugate in Ribi adjuvant. Antisera elicited by the
      conjugates showed high titers of specific anti-LOS antibodies with complement
      dependent bactericidal activity towards M. catarrhalis strain 25238. In a mouse
      aerosol challenge model, mice immunized with both conjugates showed a significant
      enhancement of the clearance of strain 25238 from lungs as compared with the
      control mice. Although both conjugates elicited reduced (relative to unconjugated
      CD or UspA) but significant levels of anti-CD or UspA antibodies, they did not
      show synergetic effects with anti-LOS antibodies on the bactericidal activity or
      the pulmonary bacterial clearance. Nevertheless, CD and UspA are safe and
      effective new carriers for dLOS-based or other potential carbohydrate-based
      conjugate vaccines to help thymus-independent carbohydrate antigens for
      production of anti-carbohydrate antibodies against target pathogens.

PMID- 15145455
TI  - Serological and molecular characterization of leptospira serovar Kenya from
      captive African giant pouched rats (Cricetomys gambianus) from Morogoro Tanzania.
AB  - Two identical leptospiral isolates coded Sh9 and Sh25 obtained from the urine of
      captive African giant pouched rats (Cricetomys gambianus), destined for use as
      biodetector of antipersonnel landmines were typed as serovar Kenya using cross
      agglutination absorption test and DNA fingerprinting with the insertion element
      sequences IS1533 and IS1500 derived primers. The two isolates were previously
      characterized using cultural and serological-microagglutination test as
      pathogenic leptospires of the serogroup Ballum, closely related to serovars Kenya
      and Peru. To our knowledge, this is the first reported in-depth characterization
      of leptospira isolates from Tanzania.

PMID- 15145456
TI  - Thymocyte depletion during acute Trypanosoma cruzi infection in C57BL/6 mice is
      partly reverted by lipopolysaccharide pretreatment.
AB  - Infection with Trypanosoma cruzi in C57BL/6 mice leads to a progressive fatal
      disease accompanied by thymocyte depletion, which is not related with a higher
      parasite burden but with increased serum levels of tumour necrosis factor alpha
      (TNF- alpha). Because this situation may result from an excessive inflammatory
      syndrome, mice were now given anti-TNF-alpha mAbs throughout their acute
      infection, or subjected to a LPS desensitization protocol before parasite
      challenge. Treatment with anti-TNF-alpha mAbs failed to ameliorate thymocyte
      depletion but shortened survival time and increased parasite load. Pretreatment
      with LPS (desensitization followed by a sublethal LPS dose) prolonged survival
      time with a trend to reduce parasitemias and TNF-alpha serum concentrations.
      Given that pentoxifylline (PTx) interferes with in vitro LPS tolerance,
      experiments by administering PTx in combination with the tolerance-inducing LPS
      doses were also performed. Such schedule significantly reduced mortality, TNF
      alpha and IL-6 serum concentrations, and CD4+ CD8+ thymocyte loss. LPS
      pretreatment allowed a better infection control and protected from the
      accompanying tissue damage.

PMID- 15145457
TI  - Structure of the O-polysaccharide and serological cross-reactivity of the
      Providencia stuartii O33 lipopolysaccharide containing 4-(N-acetyl-D-aspart-4
      yl)amino-4,6-dideoxy-D-glucose.
AB  - The O-polysaccharide of Providencia stuartii O33 was obtained by mild acid
      degradation of the lipopolysaccharide and the following structure of the
      tetrasaccharide repeating unit was established: -->6)-alpha-D-GlcpNAc-(1-->4)
      alpha-D-GalpA-(1-->3)-alpha-D-GlcpNAc-(1-->3)-beta-D-Quip4N(Ac-D-Asp)-(1-->,
      where d-Qui4N(Ac-D-Asp) is 4-(N-acetyl-D-aspart-4-yl)amino-4,6-dideoxy-D-glucose.
      Structural studies were performed using sugar and methylation analyses and NMR
      spectroscopy, including conventional 2D 1H, 1H COSY, TOCSY, NOESY and 1H, 13C
      HSQC experiments as well as COSY and NOESY experiments in an H2O-D2O mixture to
      reveal correlations for NH protons. The O-polysaccharide of P. stuartii O33
      shares an alpha-D-GlcpNAc-(1-->3)-beta-D-Quip4N(Ac-D-Asp) epitope with that of
      Proteus mirabilis O38, which seems to be responsible for a marked serological
      cross-reactivity of anti-P. stuartii O33 serum with the lipopolysaccharide of the
      latter bacterium. P. stuartii O33 is serologically related also to P. stuartii
      O4, whose O-polysaccharide contains a lateral beta-D-Qui4N(Ac-L-Asp) residue.

PMID- 15145458
TI  - Anti-complement effects of lactoferrin-derived peptides.
AB  - Lactoferrin is an important biological molecule with many functions such as
      modulation of the inflammatory response, iron metabolism and antimicrobial
      defense. One effect of lactoferrin is the inhibition of the classical complement
      pathway. This study reports that antimicrobial peptides derived from the N
      terminal region from both human and bovine lactoferrin, lactoferricin H and
      lactoferricin B, respectively, inhibit the classical complement pathway. No
      inhibitory effect of these peptides was observed on the alternative complement
      pathway in an AP50 assay. However, lactoferricin B reduced the inhibitory
      properties of serum against Escherichia coli in a concentration dependent manner.
      These results suggest that the N-terminal region of lactoferrin is the important
      part in the inhibition of complement activation and that these peptides possess
      other important properties than their antimicrobial effect.

PMID- 15145459
TI  - Evaluation of a standardized F1 capsular antigen capture ELISA test kit for the
      rapid diagnosis of plague.
AB  - Rapid detection of soluble F1 capsular antigen in serum, bubo fluid or urine of
      patients proved to be a valuable tool in the presumptive diagnosis of plague. We
      evaluated a F1 capsular antigen capture ELISA resembling a commercially available
      test kit. The minimal detectable concentration was 4 ng/ml. The specificity was
      100% when investigating 47 sera from healthy Malagasy subjects and 98.4% when 365
      sera from German blood donors were studied. Sensitivity was determined on sera
      (n=11) and buboes (n=18) from bacteriologically confirmed Malagasy plague
      patients. Sensitivity was 90.1% for serum and 100% for buboes. A standardized F1
      capsular antigen capture ELISA test kit might be well suited for the early
      detection of plague particularly in non-endemic areas where clinical
      microbiological laboratories have only limited access to alternative techniques
      for rapid identification of Yersinia pestis.

PMID- 15145460
TI  - Polymorphism in NOD2, Crohn's disease, and susceptibility to pulmonary
      tuberculosis.
AB  - The nucleotide oligomerization binding domain 2 gene (NOD2) encodes an
      intracellular receptor for bacterial components, which is expressed in monocytes
      and is associated with Crohn's Disease (CD). This finding, along with
      epidemiological evidence, supports a role for infection in the pathogenesis of
      CD. Speculation that mycobacteria are involved in CD led us to investigate NOD2
      in susceptibility to tuberculosis (TB), a global public health problem caused by
      Mycobacterium tuberculosis. CD-associated NOD2 variants were absent in a case
      control study of 640 Gambians, where CD is rare. Novel NOD2 promoter
      polymorphisms were identified but showed no association with TB in this African
      population sample.

PMID- 15145462
TI  - Regulation of proinflammatory mediator production in RAW264.7 macrophage by
      Vibrio vulnificus luxS and smcR.
AB  - Vibrio vulnificus causes fatal septicemia in human hosts, which is the
      consequence of raw shellfish consumption. The mortality following septicemia is
      dependent on the in vivo production of inflammatory mediators, including tumor
      necrosis factor-alpha (TNFalpha). The present study was set up to investigate the
      association of quorum sensing in V. vulnificus with the host immune response. The
      effect of quorum sensing on cytotoxicity and the production of proinflammatory
      mediators was examined using the murine macrophage cell-line RAW264.7.
      Cytotoxicity was determined by measuring lactate dehydrogenase release in the
      culture medium. Extracellular products from luxS- and smcR-deficient mutants
      exhibited weak cytotoxic effects on RAW264.7 cells. The production of the
      proinflammatory cytokines TNFalpha, IL-1beta and IL-6 was measured with real-time
      PCR and ELISA, and production was measured with Griess reagents. Mutation of both
      luxS and smcR delayed the transcription of TNFalpha, IL-1beta and IL-6 genes.
      Also, levels of both TNFalpha and nitric oxide induced by luxS- and smcR
      deficient mutants were significantly lower than those induced by parent strains.
      These results suggest that quorum sensing could be involved in the modulation of
      TNFalpha and nitric oxide produced from host cells by regulating virulence
      factors, and that V. vulnificus facilitates its host's mortality and bacterial
      survival by enhancing virulence on host cells.

PMID- 15145461
TI  - The Helicobacter pylori plasticity region locus jhp0947-jhp0949 is associated
      with duodenal ulcer disease and interleukin-12 production in monocyte cells.
AB  - Colonization with Helicobacter pylori always results in chronic gastritis, which
      is controlled by infiltration of mononuclear cells and the subsequent release of
      cytokines like interleukin (IL)-12. To identify H. pylori factors involved in
      inducing cytokine production in mononuclear cells, a random H. pylori mutant
      library was screened for the inability to induce IL-12 production in monocyte THP
      1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent
      twofold decrease in the amount of IL-12 induction compared to the parental strain
      1061 (P <0.01). Further characterization of mutant M1 revealed that the kanamycin
      resistance cassette had integrated in the jhp0945 gene, which is situated in an
      H. pylori strain-specific plasticity region. Three reference strains possessing
      this plasticity region induced significantly higher amounts of IL-12 when
      compared to the H. pylori 26695 reference strain, which does not possess this
      plasticity region. The role in disease outcome of jhp0945 as well as the
      neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch
      population cohort. Firstly, the presence of jhp0947 was completely linked with
      that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with
      the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and
      jhp0949 genes, but not of jhp0945, was significantly associated with duodenal
      ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947
      jhp0949 locus may be a novel putative H. pylori marker for disease outcome
      independent of the cag PAI.

PMID- 15145464
TI  - On the non-significance of internal versus external auditory hallucinations.
AB  - Traditionally, auditory hallucinations (AHs) heard outside the head have been
      regarded as more pathological than those heard inside, partly on the basis that
      internal AHs are conceptually closer to normal thinking than external AHs. Our
      data show that many patients hear AHs both internally and externally, and there
      were very few associations between location and demographic and clinical
      characteristics of the patients or with other characteristics of the AHs
      themselves. There was evidence that AHs heard internally were associated with
      better insight than those heard externally. Of those patients whose AHs included
      commands, greater proportions of those who heard them externally said they could
      resist than those who heard them internally or in both locations. There appears
      to be no consistent differential impact and effect of internal and external AHs,
      and there was no support for the historical view that internal AHs are more
      benign.

PMID- 15145465
TI  - Affective reactivity of speech and emotional experience in patients with
      schizophrenia.
AB  - Communication disturbances are exacerbated by stress in patients with
      schizophrenia, a phenomenon known as affective reactivity of speech. However, a
      subset of these patients, those with the deficit syndrome, is characterized by a
      diminished capacity to experience emotion. We examined affective reactivity in
      the natural speech of schizophrenia patients with and without the deficit
      syndrome, with the expectation that deficit syndrome patients would evidence
      lower levels of affective reactivity. Two 10-min conversational speech samples
      were collected from each of 13 deficit syndrome patients, 22 nondeficit patients
      and 26 healthy control subjects. One speech sample from each participant was on
      the topic of emotionally negative, stressful memories, and the other was on
      emotionally positive, nonstressful memories. The audiotaped speech samples were
      analyzed blindly for frequencies of referential communication failure. All three
      groups showed significantly higher frequencies of communication disturbances in
      the emotionally negative speech sample than the positive speech sample.
      Nondeficit patients showed greater affective reactivity of speech than either
      deficit patients or controls. Conversely, deficit patients' speech was not more
      reactive to emotion than the speech of the control group. These results suggest
      that emotion-related variables mediate the relationship between stress and
      language symptom exacerbations in at least some patients with schizophrenia.

PMID- 15145463
TI  - Transcriptional regulation of Salmonella enterica serovar Typhimurium genes by
      bile.
AB  - DNA microarrays and two-dimensional (2-D) gel electrophoresis were utilized to
      analyze the global effect of bile on transcription and protein synthesis in
      Salmonella enterica serovar Typhimurium. Two bile-regulated proteins, YciF and
      PagC, were identified by 2-D gel electrophoresis and mass spectrometry
      fingerprinting. The operon yciGFE-katN demonstrated increased transcriptional
      activity in the presence of bile. While this operon has previously been shown to
      be RpoS-regulated, data from this study suggested that yciGFE-katN is regulated
      by bile independent of RpoS. The PhoP-PhoQ-regulated PagC is decreased in the
      presence of bile. Characterization of the untranslated leader of pagC
      demonstrated that a 97-bp region is necessary for the bile-mediated repression of
      this promoter. Analysis of data from the DNA microarray revealed an effect of
      bile on important global mechanistic pathways in S. enterica serovar Typhimurium.
      Genes involved in type III secretion-mediated invasion of epithelial cells
      demonstrated an overall repression of transcription in the presence of bile,
      corroborating previously reported data from this laboratory [Infect. Immun. 68
      (2000) 6763]. In addition, bile-mediated transcriptional repression of genes
      involved in flagellar biosynthesis and motility was observed. These data further
      demonstrate that bile is an important environmental signal sensed by Salmonella
      spp. and that bile plays a role in regulating bacterial gene expression in
      multiple virulence-associated pathways.

PMID- 15145466
TI  - Effect of orthography on the verbal fluency performance in schizophrenia:
      examination using Japanese patients.
AB  - Letter fluency performance is less impaired than the category fluency performance
      in alphabetical-language speakers with schizophrenia. The purpose of this study
      was to determine whether the same pattern in the performance on the two verbal
      fluency tasks exists in subjects using a non-alphabetical language. In the
      Japanese orthography, there is one-to-one correspondence between sound (syllable)
      and graphemes ("kana" script), in contrast to one-to-many associations in
      alphabetical languages (e.g. English, French). The category fluency task (ANIMAL,
      FRUIT) and the letter fluency task ("KA", "TA" in "kana" script) were
      administered on 38 patients with schizophrenia and the equal number of normal
      controls. In order to examine the influence of psychotic symptoms on the verbal
      fluency performance, the Scale for the Assessment of Positive Symptoms (SAPS) and
      the Scale for the Assessment of Negative Symptoms (SANS) were administered. The
      patients performed significantly worse both in the letter- and category fluency
      tasks compared with control subjects. However, performance on the letter fluency
      task and category fluency task was similarly impaired in Japanese patients with
      schizophrenia, unlike the results in previous studies with alphabetical-language
      speakers. On the other hand, Alogia symptoms, as assessed by SANS, was a
      significant predictive variable in the regression model for the category fluency
      task score (ANIMAL), whereas the factor of the other domains of negative symptoms
      as a whole was a significant predictive variable in the model for the letter
      fluency task score (TA), which confirmed the findings in previous studies with
      alphabetical-language subjects. These results suggest that the pattern of
      impairment in the verbal fluency performance in schizophrenia is dependent on the
      specific language systems used by the patients although the degradation of the
      verbal fluency performance is influenced by some types of negative symptoms
      irrespective of the language system.

PMID- 15145467
TI  - Interpersonal attributional biases in hallucinatory-prone individuals.
AB  - Research in the area of auditory hallucinations has found that the occurrence of
      a hallucinatory experience is mediated, in part, by a bias towards making an
      external attribution for private events and experiences. The current study
      examined whether external attributional biases in hallucinators extend to their
      interpretation of social-cognitive interpersonal events. University students
      scoring high and low on the Launay-Slade Hallucination Scale (LSHS) were compared
      on self-report measures of locus-of-control (LOC) orientation, psychosis
      proneness and on the Phares [Journal of Abnormal and Social Psychology 54 (1957)
      339-342] "betting task" designed to encourage internal locus-of-control
      attributions. We predicted that high LSHS scorers would be less susceptible to a
      reinforcement paradigm designed to encourage internal locus-of-control judgments
      compared to low LSHS scorers. Consistent with our hypothesis, results revealed
      that hallucinatory predisposed individuals were less likely to show increased
      success expectancy following reinforcement and to decrease success expectancy
      following failure than were non-hallucinatory predisposed subjects. These
      findings suggest that hallucinatory-prone individuals not only make external
      attributions for private events and experiences, but are more likely to make
      external attributions to social-interpersonal events as well. We also found that
      subjects' severity of hallucinatory predisposition was significantly associated
      with their Chapman Magical Ideation and Perceptual Aberration scale scores. These
      results are consistent with past studies that suggest that hallucinatory subjects
      are more vulnerable to suggestion and support the notion that external loci of
      control over interpersonal experiences are associated with increased psychosis
      vulnerability.

PMID- 15145468
TI  - Persecutory beliefs, attributions and theory of mind: comparison of patients with
      paranoid delusions, Asperger's syndrome and healthy controls.
AB  - Schizophrenia patients with persecutory delusions and patients with Asperger's
      syndrome were compared using two measures of theory of mind (ToM; the ability to
      infer mental states in other people), the Hints task, and the Reading the Mind in
      the Eyes task, and a new measure of attributional style (style of inferring the
      causes of important events), the Attributional Style Structured Interview (ASSI).
      Paranoid beliefs were measured using Fenigstien and Vanable's Paranoia Scale
      (PS). The deluded group had the highest scores on the Paranoia Scale but the
      scores of the Asperger's group's were higher than those of the controls. Paranoid
      patients made more external-personal attributions for negative events than the
      Asperger's and control groups. Both the paranoid and Asperger's groups performed
      poorly on the ToM tasks compared to the controls. The findings support the
      hypothesis that both ToM and attributional abnormalities contribute to paranoid
      delusions. The lack of attributional abnormalities in the Asperger's group
      suggests that their low-level paranoid symptoms arise as a consequence of
      different mechanisms than those involved in psychotic delusions.

PMID- 15145470
TI  - 'Theory of mind' in violent and nonviolent patients with paranoid schizophrenia.
AB  - The role of mentalizing abilities (or theory of mind) and empathic abilities in
      violent behavior were studied in 24 hospitalized males with paranoid
      schizophrenia (ICD-10). Patients were divided into violent and nonviolent groups
      based on their history of committing violent acts against others. To examine
      these abilities, patients heard a series of 12 short scenarios depicting social
      situations followed by questions that require making mental state or empathic
      inferencing. Our results show that violent patients have more difficulties than
      nonviolent patients in tasks involving empathic inferencing, and better abilities
      in inferring cognitive-mental states in others. In addition, violence seems to be
      associated with a history of alcohol and drug abuse, young age, and the hostility
      component of the Brief Psychiatric Rating Scale. Logistic regression analyses
      suggest that violence is associated with the combination of hostility towards
      others, good mentalizing abilities and poor empathy. These results are discussed
      in light of recent theories on violent behavior in psychiatric populations.

PMID- 15145469
TI  - Symptoms and interference from memory in schizophrenia: evaluation of Frith's
      model of willed action.
AB  - The present study was undertaken to test Frith's [The Cognitive Neuropsychology
      of Schizophrenia, 1992. Erlbaum (UK) Taylor and Francis, East Sussex] model which
      states that certain symptoms of schizophrenia arise from diminished capacity to
      regulate willed (goal-directed) and stimulus-driven action systems. A total of
      107 patients were administered the Rey Auditory Verbal Learning Test (RAVLT), a
      task that on interference trials requires individuals to recall target material
      while suppressing non-target distracting stimuli from memory. Symptom ratings
      were obtained using the SANS/SAPS [Andreasen, N.C., 1984. Scale for the
      Assessment of Negative Symptoms/Scale for the Assessment of Positive Symptoms
      [Manual] University of Iowa Press, Iowa City]. It was predicted that (1) negative
      symptoms would result in diminished recall, reflecting compromised activation of
      the willed action system, and (2) disorganized symptoms would be associated with
      heightened interference susceptibility resulting from diminished ability to
      suppress the stimulus-driven action system. Results revealed that diminished
      recall was related to negative, but not disorganized or positive symptoms.
      Symptom ratings were also evaluated in a subset of patients with intrusion error
      data (n=38). In this subset, it was found that patients who committed intrusion
      errors on the interference trials evidenced more disorganized, but not negative
      or positive symptoms, than individuals failing to commit such errors. These
      findings provide some support for Frith's hypothesis that impaired regulation of
      action systems may underlie some of the specific symptoms and cognitive
      impairments of this illness.

PMID- 15145471
TI  - Olfactory identification and WAIS-R performance in deficit and nondeficit
      schizophrenia.
AB  - INTRODUCTION: An expanding database supports the notion that the deficit syndrome
      (DS) is a discrete condition within schizophrenia and recent data argues that
      Smell Identification Deficits (SID) may have a primary relationship with its
      pathophysiology. If so, then the relationship of University of Pennsylvania Smell
      Identification Test (UPSIT) scores with other neurocognitive measures in DS
      patients may point to the neural substrate of the deficit syndrome. METHOD: We
      examined the relationship of UPSIT scores and Wechsler Adult Intelligence Scale
      Revised (WAIS-R) performance in 46 DSM-IV schizophrenia patients. The Schedule
      for the Deficit Syndrome (SDS) interview was used to subgroup the sample into 13
      DS and 33 nondeficit syndrome (NDS) patients. RESULTS: DS and NDS groups had
      similar mean ages, age of onset, and GAF scores, but DS patients had fewer years
      of education. DS and NDS patients also did not differ in full scale, verbal or
      performance IQ or in any WAIS-R subtest. However, UPSIT scores were significantly
      worse in the DS patients, most of whom met criteria for a clinically meaningful
      olfactory impairment. In DS patients, UPSIT scores were significantly correlated
      with Performance IQ, Block Design, and Object Assembly, all of which are
      associated with complex visual-motor organizational function thought to be
      mediated by parietal circuitry. UPSIT scores in NDS patients were significantly
      related with Vocabulary, Similarities, and Digit Symbol subtests, which are
      indicative of verbal functioning. CONCLUSION: These preliminary data support
      previous findings suggesting that in addition to frontal neuropsychological
      abnormalities, DS patients may have greater performance impairments on tasks
      associated with parietal functioning. Our findings furthermore suggest that the
      parietal circuitry may be a conspicuous substrate for impaired odor
      identification ability in these patients. The lesser abnormalities in UPSIT
      ability in NDS patients may be attributed to verbal ability. These data are
      preliminary and further investigations with larger samples are needed to support
      our findings.

PMID- 15145472
TI  - Neurocognition and long-term prediction of quality of life in outpatients with
      severe and persistent mental illness.
AB  - The present study examined the predictive validity of neuropsychological measures
      to quality of life (QOL) indicators in 30 outpatients with severe and persistent
      mental illness (SPMI), an average of 15 years post-testing. Outcome measures
      included subscale scores on the Brief Quality of Life Inventory (BQOLI). Results
      of several stepwise multiple regressions revealed that memory was predictive of
      income, satisfaction with daily activities, and general health. Executive
      functioning was predictive of contact with family and financial support. Motor
      skills were predictive of satisfaction with family contact, and working memory
      was predictive of victimization and satisfaction with social contacts. Discussion
      focused on neurocognition as a predictor of QOL, clinical implications, and the
      potential for improving QOL through cognitive interventions.

PMID- 15145473
TI  - Comparative neuropsychological function in obsessive-compulsive disorder and
      schizophrenia with and without obsessive-compulsive symptoms.
AB  - Executive function deficits are seen in both schizophrenia and obsessive
      compulsive disorder (OCD), but research suggests that dorsolateral prefrontal
      (DLPF) dysfunction is associated with schizophrenia and orbitofrontal (OBF)
      dysfunction is associated with OCD. As part of a comprehensive neuropsychological
      assessment, the Bechara Gambling Task (BGT) was used to assess OBF function and
      the Wisconsin Card Sorting Test (WCST) was used to assess DLPF function among
      three groups: 26 individuals with schizophrenia/schizoaffective disorder with
      obsessive-compulsive symptoms (SCZ+), 28 individuals with
      schizophrenia/schizoaffective disorder without obsessive-compulsive symptoms (SCZ
      ), and, 11 individuals with OCD. It was predicted that the SCZ+ group and the OCD
      group would show impairments in OBF function, as compared to the SCZ- group, and
      that the SCZ+ and SCZ- groups would show impairments in DLPF function, as
      compared to the OCD group. It was also predicted that the SCZ+ group would
      perform more poorly than the SCZ- and OCD groups in a number of other cognitive
      domains. Contrary to expectation, no divergence between groups was seen on tests
      of executive function. Instead, there was a statistical trend for the SCZ+ and
      SCZ- groups, when combined, to perform worse than individuals with OCD on the
      measure of OBF. Although not significant at the designated alpha level, the
      profile results showed that the SCZ+ group performed slightly below the OCD and
      SCZ- groups across nearly all neuropsychological domains.

PMID- 15145474
TI  - Self-assessed cognitive dysfunction and objective performance in outpatients with
      schizophrenia participating in a rehabilitation program.
AB  - OBJECTIVE: To explore the pattern of associations between self-assessed and
      objective neuropsychological performance in a sample of outpatients with
      schizophrenia participating in a rehabilitation program. METHOD: The Subjective
      Scale to Investigate Cognition in Schizophrenia (SSTICS) [Compr. Psychiatry 44
      (2003) 331] was used to assess cognitive complaints in 73 subjects with
      schizophrenia. Visuo-spatial tests of the Cambridge Neuropsychological Test
      Automated Battery (CANTAB) [Cogn. Neuropsychiatry 3 (1998) 45] were administered
      as objective measures. RESULTS: Cognitive complaints in several cognitive domains
      were mainly correlated with a true difficulty in memory. Higher SSTICS attention
      scores, i.e. increased complaints, were associated with poorer CANTAB explicit
      visual memory and planning performances. Higher SSTICS executive functioning
      scores were associated with poorer CANTAB explicit visual memory scores.
      CONCLUSION: These findings suggest that outpatients with schizophrenia express
      some cognitive difficulties. However, the cognitive nature of these subjective
      complaints does not strictly correspond with objective performances. These
      results also suggest that theoretical constructs of cognitive functions do not
      always have ecological validity. Thus, subjective cognitive complaints should be
      taken into account in assessment of patient well-being, but cannot be used as a
      substitute to objective cognitive measures. The simultaneous use of subjective
      and objective measures of cognitive dysfunction may provide a more complete
      picture of individual rehabilitation targets in patients with schizophrenia.

PMID- 15145475
TI  - The role of subclinical paranoia on social perception and behavior.
AB  - The purpose of this study was to investigate the effects of subclinical paranoia
      on social perception and behavior. Two groups of participants, those high and low
      in subclinical paranoia, were identified based on extreme scores on the Paranoia
      Scale (PS). As expected, persons high in subclinical paranoia had greater
      depression, social anxiety, self-consciousness, and lower self-esteem compared to
      persons low in subclinical paranoia. In addition, persons high in subclinical
      paranoia performed worse than persons low in subclinical paranoia on laboratory
      measures of emotion perception and on an in vivo social perception task. Finally,
      behavioral differences between these two groups were revealed: Persons high in
      subclinical paranoia sat further away from the examiner and took longer to read
      the consent form than low-paranoia persons. These behavioral differences were not
      due to the group differences in clinical functioning, indicating that level of
      paranoia generally accounted for these findings.

PMID- 15145477
TI  - Are the negative symptoms of schizophrenia consistent with an autistic spectrum
      illness?

PMID- 15145476
TI  - Affectivity in the problem-solving interactions of schizophrenia patients and
      their family members.
AB  - This study sought to examine the relationship between symptomatology and the
      affect expressed between individuals with schizophrenia and their family members.
      It was hypothesized that, because of their impact on patient social behavior and
      potential burden on relatives, greater negative symptoms would be associated with
      less emotional expression in patients but would be related to the greater
      expression of negative emotions in their relatives within a problem-solving
      discussion. Informed by research on the structure of emotion, a broad assessment
      of affect, including Negativity, Positivity, and Disengagement, was utilized to
      examine affect expressed by patients with schizophrenic disorders (N=91) and
      their family members during videotaped problem-solving discussions. Although
      individuals with schizophrenia were comparable to their family members in
      displays of Negativity, patients displayed less Positivity and greater
      Disengagement. Greater negative symptoms (in particular blunted or flat affect)
      were related to a general diminution of affective expression in the schizophrenia
      group. However, negative symptoms were unrelated to the emotional expression of
      family members. Other symptoms such as thought disorder and mood symptoms of
      anxiety, depression, and hostility were not related to displays of affect by
      either patients or their family members. The findings indicate the importance of
      examining domains of affect other than negativity and demonstrate that negative
      symptoms are related to interpersonal displays of affect in schizophrenia.
      Additionally, these results suggest that schizophrenic symptoms, by themselves,
      may contribute little to the conflict between patients and their family members.

PMID- 15145478
TI  - Glial fibrillary acidic protein and glutamic acid decarboxylase 65 and 67 kDa
      proteins are increased in brains of neonatal BALB/c mice following viral
      infection in utero.

PMID- 15145480
TI  - Scaphoid nonunions treated with vascularised bone grafts: MRI assessment.
AB  - PURPOSE: To assess the value of MR imaging (MRI) with regard to union, graft
      viability and proximal pole bone marrow status, after use of vascularized bone
      grafts for treating scaphoid nonunions. MATERIALS AND METHODS: Vascularized bone
      grafts from the distal radius were used to treat 47 scaphoid nonunions resulting
      from fractures or enchondromas. Clinical and imaging evaluation was used for the
      pre- and postoperative assessment of all patients. Apart of conventional
      radiographs obtained in all cases, 15 patients were also assessed postoperatively
      with MRI at 3 months. From these 15 patients, eight were assessed preoperatively
      with MRI whereas nine had serial MRI evaluations at 6 and 12 months. The clinical
      follow-up time of this subgroup of 15 patients ranged from 6 to 27 months.
      RESULTS: All patients showed clinical signs of union within 12 weeks form the
      procedure and at the latest follow-up they experienced complete (10 cases) or
      almost complete (five cases) relief from pain. Both plain and contrast-enhanced
      MRI obtained at 3 months showed viability of the bone graft in all cases. At 3
      months union was established with plain radiographs in 12 patients at both sides
      of the graft and in three patients between the graft and proximal pole. At 3
      months plain MRI showed nonunion in four patients (two between graft and proximal
      pole, two between graft and distal pole and one at both sides of the graft)
      whereas contrast-enhanced MRI revealed only one case of nonunion between graft
      and proximal pole. Four patients were considered to have osteonecrosis of the
      proximal pole intraoperatively. Two of them showed necrosis of the proximal pole
      with preoperative and postoperative plain radiographs and three of them with
      plain postoperative MRI. Contrast-enhanced MRI at 3 months showed postoperative
      reversal of necrotic changes in all four scaphoids. MRI also revealed bone marrow
      oedema of the carpal bones surrounding the scaphoid in 14 cases. Serial MRI at 6
      and 12 months, obtained in nine patients, revealed resolution of the bone marrow
      oedema of the surrounding bones and full graft incorporation in all cases.
      CONCLUSION: Contrast-enhanced MRI is able to demonstrate the early union after
      treatment of scaphoid nonunions with vascularised bone grafts allowing thus
      earlier mobilisation. In addition, MRI can assess the viability of the proximal
      pole and the graft as well as the postoperative bone marrow oedema-like lesions
      of the surrounding bones.

PMID- 15145481
TI  - MR imaging findings in early osteoarthritis of the knee.
AB  - PURPOSE: To carry out a modern diagnostic survey among patients with a clinical
      and radiological diagnosis of early osteoarthritis of the knee. MATERIALS AND
      METHODS: A magnetic resonance imaging survey was performed on 70 patients (82
      knees) with a mean age of 59 years. (range, 40-71 years) who had chronic knee
      pain, clinical diagnosis of early osteoarthritis of the knee and conventional
      knee radiographs classified as 1 and 2 on the Kellgren-Lawrence scale. RESULTS: A
      variety of different disorders was found; degenerative meniscal lesions with or
      without ruptures of the anterior cruciate ligament in 70.7% of the knees,
      osteonecrosis of the femoral and tibial condyles in 9.75%, osteophytes and
      degenerative articular cartilage lesions in 8.54%, transient osteoporosis in
      2.44% and benign neoplasms and cysts in 6.1%. CONCLUSIONS: The existence of such
      a heterogenous group of disorders in these "early osteoarthritic knees" may
      explain failures in treatment and it may justify a modern MRI imaging approach to
      proper diagnosis.

PMID- 15145482
TI  - Evaluation of meniscal repair with serial magnetic resonance imaging: a
      comparative study between conventional MRI and indirect MR arthrography.
AB  - OBJECTIVE: To prospectively investigate the healing process of meniscal repair
      with plain magnetic resonance imaging (MRI) and indirect MR arthrography and to
      compare the two methods. MATERIALS AND METHODS: Twenty patients with an
      arthroscopic meniscal repair without clinical symptoms underwent conventional and
      indirect MR arthrography of the affected knee, 3, 6 and 12 months after the index
      operation applying a T1-w Spin Echo sequence in three planes. The size of the
      tear gap was measured on transverse images. The signal-to-noise ratio and the
      configuration of the abnormal signal were evaluated in the coronal images.
      RESULTS: All patients demonstrated abnormal signal intensity at the side of the
      meniscal repair. The size of the gap at the previous tear side, reduced
      significantly by 45 and 40% on conventional MRI and indirect MR arthrography
      respectively, from 3 months to 1 year (P < 0.05). The signal-to-noise ratio of
      the intrameniscal abnormal signal reduced significantly and approximately 50%
      from 3 to 6 months, and from 6 to 12 months postoperatively, as demonstrated with
      indirect MR arthrography. However, as opposed to normal meniscus, the signal-to
      noise ratio of the abnormal area remains 5.5 times higher 12 months
      postoperatively. In contrast, the reduction of signal-to-noise ratio of the
      abnormal area at conventional MRI was not significant even from 3 to 12 months.
      In 90% of the cases, the indirect MR arthrography showed the intrameniscal
      abnormal signal on plain MRI, to extend to the articular surface as opposed to
      25% on plain MRI. CONCLUSION: With indirect MR arthrography, the natural process
      of meniscal healing can be evaluated. Significant reduction of the size of the
      tear gap and significant reduction of the signal-to-noise ratio of the abnormal
      signal as well as its configuration are the main parameters interpretating the
      normal healing process.

PMID- 15145483
TI  - MR imaging findings in transient osteoporosis of the hip.
AB  - PURPOSE: The authors sought to describe the magnetic resonance (MR) imaging
      findings including perfusion imaging, in association with the course of acute
      bone marrow oedema syndrome (aBMEs), in a group of patients with acute hip pain
      and a final diagnosis of transient osteoporosis of the hip (TOH). MATERIALS AND
      METHODS: From 217 patients referred with a probable diagnosis of avascular
      necrosis (AVN) of the femoral head, we identified 42 patients who had clinical
      and radiographic findings not relevant to AVN. MR imaging examinations were
      performed on a 1.0T scanner. Perfusion imaging was performed in 20 patients. The
      bone marrow oedema (BME) was classified in four stages. In addition, the presence
      or absence of oedema in the subchondral area and the presence of other
      subchondral lesions were recorded. Acetabular bone marrow was also assessed for
      the presence of oedema. The quantitative measurements included: maximum size of
      the effusion, percentage of enhancement (PE) and time of peak enhancement of
      abnormal marrow compared to the first pass, on the perfusion images. RESULTS:
      Osteopenia was present on plain radiographs in 87% of cases. The most common
      pattern of BME was extending to the femoral head and neck. Acetabulum was
      involved in 16.6%. In 22.6% the BME spared the subchondral region of the femoral
      head. There were two cases (4.7%) with subchondral changes. A joint effusion was
      noted in 33 of the 42 patients. On perfusion imaging, a delayed peak enhancement
      was noted in 20 patients between 40 and 65 s after the first pass of contrast. No
      patient had any evidence of femoral head collapse or change in sphericity on
      follow-up MRI. None of the patients developed avascular necrosis in a time frame
      of 18 months from the onset of the acute hip pain. CONCLUSION: The aBMEs MR
      imaging pattern varies and is most commonly appearing on X-rays as osteopenia.
      Absence of subcondral lesions, delayed peak enhancement of the abnormal marrow on
      perfusion images, and sparing of subchondral zone from marrow oedema are MR
      imaging findings highly correlated to TOH.

PMID- 15145485
TI  - Lipomatous tumors of soft tissue: MR appearance with histological correlation.
AB  - There is a broad spectrum of lipomatous tumors that involve soft tissues
      including ordinary lipomas, variants of lipomas, heterotopic lipomas,
      lipomatosis, hibernomas and liposarcomas. The recognition of these tumors is
      important to avoid diagnostic pitfalls. The MR imaging appearance of the lesion,
      including location, shape and internal architecture, suggests the diagnosis of
      lipomatous tumors. The signal intensity on T1-, T2-, fat-suppressed T2-weighted
      (FS-T2) images or short tau inversion recovery (STIR), T1- and fat-suppressed T1
      weighted images after Gd-DTPA administration can be a useful aid in
      distinguishing between biologically different types of lipomatous tumors. The
      imaging features are often characteristic and reflect the histological pattern of
      the tumors. We present an overview of the lipomatous tumors and we correlate MR
      imaging appearance with histological findings.

PMID- 15145484
TI  - Assessment of the skeletal status by MR relaxometry techniques of the lumbar
      spine: comparison with dual X-ray absorptiometry.
AB  - PURPOSE: To measure lumbar spine T2*, T2, T2' and T1 MR relaxometry parameters
      and compare them with lumbar spine bone mineral density (BMD) in a group of
      postmenopausal women. MATERIALS AND METHODS: Lumbar spine T2*, T2, T2' and T1 MR
      relaxometry parameters and BMD values were assessed in 101 postmenopausal women
      (mean age: 61.8 +/- 7.1 (1 S.D.) years); of them 63 referred to as control
      subjects (group A, BMD T-scores > or = -2.5 S.D.) and 38 as osteoporotic (group
      B, BMD T-scores < -2.5 S.D.). All magnetic resonance imaging (MRI) examinations
      were performed on an 1.5 T imaging system using: (a) a 2D single slice multi echo
      (32 echoes) gradient echo (MEGRE) sequence (TR/TE1/TE32/FA: 160/2.7/74.93 ms/25
      degrees for the T2* measurement, (b) a respiratory gated 2D single slice Multi
      Echo (16 echoes) Spin Echo (MESE) sequence (TR/TE1/TE16/FA: 2000-2500/22.5/360
      ms/90 degrees) for the T2 measurement and (c) a 2D single slice multi TI (18
      repeats) turbo Fast Low Angle Shot (turbo FLASH) sequence (TR/TE/TI1/TI16/FA:
      11/4.2/10/5000 ms/10 degrees) for the T1 measurement. T2' was calculated from its
      definition equation: (1/T2' = 1/T2* - 1/T2). Lumbar spine BMD was assessed using
      DXA. RESULTS: All measured parameters showed statistically significant
      differences between groups A and B (from P < 0.05 to <0.001). All parameters
      showed significant associations with subject's age ranging from r = 0.245 (P <
      0.05) for the T2 up to r = 0.377 (P < 0.001) for the T2*. All parameters showed
      significant associations with subject's BMD measurements ranging from r = -0.184
      (P < 0.05) for the R1 = (1/T1) up to r = -0.345 (P < 0.0005) for the T2.
      CONCLUSION: Among the MR relaxometry parameters studied, T2* and T2 showed better
      discrimination of patients with osteoporosis from control subjects.

PMID- 15145486
TI  - Discrimination of hip fractures by quantitative ultrasound of the phalanges and
      the calcaneus and dual X-ray absorptiometry.
AB  - The aim of the current study was to evaluate the ability of different techniques
      used for the assessment of bone status to discriminate between postmenopausal
      women with and without hip fracture. Fifty-one postmenopausal women (mean age
      64.5 +/- 6.5) who had sustained a low energy hip fracture and 51 age-matched
      controls (mean age 64.6 +/- 6.0) were studied. Quantitative ultrasound (QUS)
      assessment was carried out using the Ubis 3000 device capable of measuring
      broadband ultrasound attenuation (BUA) and speed of sound at the calcaneus (SOSC)
      and the Sunlight Omnisense device capable of estimating speed of sound at the
      phalanges (SOSP). Femoral neck bone mineral density (BMD) was assessed using dual
      X-ray absorptiometry. Correlations between QUS variables ranged from r = 0.35 to
      0.72 and between QUS variables and BMD from r = 0.30 to 0.36. BMD was the best
      discriminator of hip fractures (odds ratio = 3.61, area under curve = 0.824). All
      QUS variables were significant discriminators of hip fractures with odds ratios
      ranging from 1.88 to 2.63 and areas under the ROC curves ranging from 0.663 to
      0.740. Among the QUS variables, the SOSP showed the best odds ratio and area
      under curve. Comparison between the areas under the ROC curve did not show any
      significant difference between SOSP, BUA and BMD. On the contrary, the difference
      between SOSC and BMD was significant (P < 0.05). In conclusion, BMD and QUS
      variables investigated in the current study were significant discriminators of
      hip fractures. The differentiation of the hip fractures by BMD was significantly
      better than that of BUA measured at the calcaneus. Moreover, BMD discriminated
      fractured patients better than BUA and SOS(P), although the difference did not
      reach statistical significance.

PMID- 15145487
TI  - Percutaneous CT-guided interventional procedures in musculoskeletal system (our
      experience).
AB  - Percutaneous interventional procedures include a broad spectrum of minimal
      invasive techniques, which are a useful diagnostic and therapeutic tool. In this
      study we present our experience in CT-guided percutaneous musculoskeletal
      biopsies, drainages of musculoskeletal abscesses, facet and sacroiliac joint
      injection and radiofrequency thermal ablation of painful metastases or osteoid
      osteomas.

PMID- 15145488
TI  - Increased frequency of white matter lesions in patients with osteonecrosis
      (WMLeOn) of the femoral head.
AB  - White matter lesions (WML) are commonly seen in cerebral MR imaging in normal and
      demented elderly people or young people suffering from migraine. We present data
      showing that WML are detected in an unexpectedly high frequency (56.9%) in
      patients with non-traumatic osteonecrosis of the femoral head compared to age and
      sex-matched controls. We designated the coexistence of WML and osteonecrosis as
      white matter lesions in osteonecrosis (WMLeON). We examined the possible
      association of WMLeON with hyperlipidaemia and other risk factors for WML or
      osteonecrosis of the femoral head. The frequency of history of corticosteroid
      treatment was statistically lower in patients with WMLeON (58.6%) compared to
      those without it (90.1%) (P = 0.03). We found no association of WMLeON with
      diabetes, stroke, hyperlipidaemia, migraine, smoking, alcohol consumption,
      hypertension, atrial fibrillation, or systemic lupus erythematosus. Although, the
      clinical significance of WMLeON is still unknown, this finding supports, at
      least, the hypothesis that non-traumatic osteonecrosis is indeed a multisystem
      disorder rather than a disease of human skeleton.

PMID- 15145489
TI  - UK population dose from medical X-ray examinations.
AB  - OBJECTIVE: To assess the annual per caput and collective effective dose to the
      United Kingdom population from medical and dental X-ray examinations. METHOD: The
      results of a detailed survey of the frequency of X-ray examinations during the
      financial year 1997/1998 were combined with contemporary data on the effective
      doses typically received by patients. The resulting per caput and collective dose
      for 1997/1998 was updated to 2001/2002 by using annual statistics on the total
      numbers of computed tomography (CT), interventional and conventional examinations
      collected by the English Department of Health. RESULTS: The annual per caput
      effective dose for the UK in 2001/2002 was estimated at 0.38 mSv. Over the last
      10 years CT has more than doubled its contribution and is now responsible for 47%
      of the collective dose from medical X-rays. The contribution from conventional
      radiographic and fluoroscopic examinations has nearly halved to about 34%.
      Interventional and angiographic procedures together contribute the remaining 19%.
      CONCLUSIONS: The annual per caput effective dose of 0.38 mSv is low in comparison
      with other countries having similarly developed systems of health-care. This is
      due to both a lower frequency of X-ray examinations per head of population and
      generally lower doses in the UK than in other developed countries.

PMID- 15145490
TI  - MRI evaluation of patellar tendon defect after harvesting its central third.
AB  - PURPOSE: the purpose of this study was to evaluate defect width of patellar
      tendon after harvest for anterior cruciate ligament reconstruction. MATERIALS AND
      METHODS: we performed MRI at various time interval after graft harvest (2-96
      months) on 28 patients who had had reconstruction of the anterior cruciate
      ligament using mid-third patellar tendon. T1 and T2 weighted axial images were
      obtained to assess donor site defect of the patellar tendon. Measurement of the
      defect width was performed at the level of menisci on the axial images. The
      patients were divided into two groups according to the time interval between
      operation and imaging. The defect width of patients with short time interval (2
      12 months) was compared to the defect width of patients with long time interval
      (12-96 months). RESULTS: the average defect width of patients with short time
      interval was 6.4 mm and it was 2.2 mm for the patients with long time interval.
      Decreased defect width was obtained from MRI images in the patients with long
      time interval. Closed donor site defect was detected in 1 out of 14 patients with
      short time interval and 6 out of 14 patients with long time interval. DISCUSSION
      AND CONCLUSION: these results show that there is no complete closure of donor
      site defect up to 1 year. However, it seems to be nearly complete closure of
      patellar tendon defect in the long time period.

PMID- 15145491
TI  - Remarkable anatomic variations in paranasal sinus region and their clinical
      importance.
AB  - With the advent of functional endoscopic sinus surgery (FESS) and coronal
      computed tomography (CT) imaging, considerable attention has been directed toward
      paranasal region anatomy. Detailed knowledge of anatomic variations in paranasal
      sinus region is critical for surgeons performing endoscopic sinus surgery as well
      as for the radiologist involved in the preoperative work-up. To be in the known
      anatomical variants with some accompanying pathologies, directly influence the
      success of diagnostic and therapeutic management of paranasal sinus diseases. A
      review of 512 (1024 sides) paranasal sinus tomographic scans was carried out to
      expose remarkable anatomic variations of this region. We used only coronal
      sections, but for some cases to clear exact diagnosis, additional axial CT scan,
      magnetic resonance imaging (MRI) and nasal endoscopy were also performed. In this
      pictorial essay, rates of remarkable anatomic variations in paranasal region were
      displayed. The images of some interesting cases were illustrated, such as the
      Onodi cell in which isolated mucocele caused loss of visual acuity, agger nasi
      cell, Haller's cell, uncinate bulla, giant superior concha bullosa, inferior
      concha bullosa, bilateral carotid artery protrusion into sphenoid sinus,
      maxillary sinus agenesis, bilateral secondary middle turbinate (SMT) and
      sphenomaxillary plate. The clinical importance of all these variations were
      discussed under the light of the literature. It was suggested that remarkable
      anatomic variations of paranasal region and their possible pathologic
      consequences should be well defined in order to improve success of management
      strategies, and to avoid potential complications of endoscopic sinus surgery. The
      radiologist must pay close attention to anatomical variations in the preoperative
      evaluation.

PMID- 15145492
TI  - Multidetector row CT angiography of the abdominal aorta and lower extremities in
      patients with peripheral arterial occlusive disease: diagnostic accuracy and
      interobserver agreement.
AB  - PURPOSE: To evaluate the accuracy of four channel multidetector row CT
      angiography (MDCTA) of the abdominal aorta and lower extremities arteries
      compared with digital subtraction angiography (DSA). MATERIALS AND METHODS: In
      our prospective study 42 patients with peripheral vascular occlusive disease (27
      M, 15 F, age range 40-79 years) underwent MDCTA and DSA within 5 days. Images
      were blindly interpreted by two radiologists. Maximum intensity projections
      (MIP), multiplanar (MPR) reformations, three-dimensional (3D) reconstructions as
      well as axial images were available for analysis of MDCTA. DSA were analyzed on
      hard copies. RESULTS: Overall sensitivity and specificity of MDCTA were 93 and
      95%, respectively, with positive and negative predictive values of 90 and 97%.
      Overall diagnostic accuracy was 94%. Normal arterial segments and 100% occlusions
      were correctly identified in all cases by MDCTA. Moderately stenotic segments
      interpretation in the calves appeared to be more controversial, but no
      statistical difference in accuracy of MDCTA in the infrapopliteal district
      arteries was noted with respect to accuracy in the more proximal arterial bed.
      Good to excellent interobserver and intraobserver agreement were observed, with k
      values greater than 0.80. CONCLUSIONS: MDCTA of the abdominal aorta and lower
      extremities is an accurate imaging modality in clinical practice when compared
      with DSA.

PMID- 15145493
TI  - The effect of maternal antibodies on the detection of bovine virus diarrhoea
      virus in peripheral blood samples.
AB  - Persistently infected animals (PI animals), that is those animals born after an
      intrauterine infection of the dam during the first 120 days of gestation, are the
      main source of bovine virus diarrhoea virus (BVD virus) in a cattle population.
      The success of any BVD virus eradication programme depends on the ability to
      detect all PI animals at a young age. The purpose of this study was to evaluate
      the use of the antigen ELISA test and the reverse transcriptase-polymerase chain
      reaction (RT-PCR) test for the diagnosis of PI animals in the presence of
      maternal antibodies, and to compare them with the classical virus isolation test.
      In this experiment, 25 calves born after an experimental infection with a mixture
      of BVD virus field strains were used. All calves were found to be positive for
      BVD virus using the virus isolation test, both before the ingestion of colostrum
      and again at 10 weeks of age. Both the virus isolation test and the antigen ELISA
      test were shown to be unreliable indicators for the diagnosis of persistent
      infections with BVD virus, when used in the presence of high levels of maternal
      antibodies. However, the RT-PCR test gave positive results even in the presence
      of high maternal antibody titres, indicating the suitability of the RT-PCR test
      for use in eradication programmes.

PMID- 15145495
TI  - Anaplasma infection in free-ranging Iberian red deer in the region of Castilla-La
      Mancha, Spain.
AB  - Organisms in the genus Anaplasma are obligate intracellular pathogens that
      multiply in both vertebrate and invertebrate hosts. The type species, Anaplasma
      marginale, causes bovine anaplasmosis and infects erythrocytes of the vertebrate
      host and undergoes a complex developmental cycle in ticks which serve as
      biological vectors. Infected cattle, wild ruminants and ticks can all serve as
      reservoirs of A. marginale. In this study, hunter killed Iberian red deer (Cervus
      elaphus hispanicus) from the region of Castilla-La Mancha in southwestern Spain
      were tested for Anaplasma infection. We found that 10% of the deer examined were
      seropositive for Anaplasma. Three A. marginale strains were subsequently obtained
      from salivary glands of Hyalomma marginatum that were removed from these deer,
      and the sequence of the major surface protein (msp)4 gene was determined for each
      strain and used for phylogenetic studies. Maximum parsimony analyses of msp4
      sequences from H. marginatum ticks in comparison with New World cattle and bison
      isolates reported previously, suggested different origins for these Spanish A.
      marginale strains. The results of this study demonstrated that Iberian red deer
      are naturally infected with Anaplasma, and may therefore serve as a wildlife
      reservoir of the pathogen. Although the link between deer infection and the
      strains of A. marginale identified in ticks was not established, H. marginatum
      and Rhipicephalus bursa were identified as potential biological vectors for A.
      marginale in this region and may effect transmission of A. marginale between deer
      and cattle populations.

PMID- 15145494
TI  - Attenuation of a virulent type 2 bovine viral diarrhea virus.
AB  - The purpose of this study was to produce an attenuated bovine viral diarrhea
      virus (BVDV) type 2 strain as a tool for identifying potential virulence markers
      in the BVDV2 genome. The attenuation of the virulent strain, BVDV2-24515, was
      accomplished by in vivo and in vitro passage. The strain was initially used to
      infect an elk (Cervus elaphus) [J. Wildl. Dis. 35 (1999) 671], re-isolated at 7
      days post-inoculation from serum, and then subsequently passaged 56 times in cell
      culture. Two groups of calves were inoculated intranasally with either BVDV2
      24515 or the putative attenuated virus, designated BVDV2-LATT. Calves inoculated
      with BVDV2-24515 had cumulative clinical scores which ranged from 6 to 53.
      Clinical signs in these calves consisted of anorexia, depression, dehydration,
      diarrhea (+/-bloody), and pneumonia. Several calves developed leukocytopenia,
      primarily a neutrocytopenia, and presented lesions of enteritis or pneumonia at
      necropsy. In contrast, cattle inoculated with BVDV2-LATT had cumulative clinical
      scores which ranged from 0 to 2. This was not significantly different from that
      of controls which received no virus (range: 0-1). Calves inoculated with BVDV2
      LATT produced high neutralizing antibody titers against BVDV2. Thus, in addition
      to its potential use as a tool for identifying virulence markers, the attenuated
      virus is also worthy of further study as a candidate virus for inclusion in a
      modified-live vaccine.

PMID- 15145496
TI  - Ehrlichia ruminantium seroprevalence in domestic ruminants in Ghana; I.
      Longitudinal survey in the Greater Accra Region.
AB  - Serum samples collected monthly over a 34-month period from cattle, sheep and
      goats in the Greater Accra Region of Ghana were tested for antibodies to
      Ehrlichia (previously Cowdria) ruminantium, the causative agent of heartwater, by
      polyclonal competitive ELISA (PC-ELISA). Maternal antibodies, detected in about
      half of animals followed from under 1 month old, declined to negative levels
      within 2-4 months. Amblyomma variegatum tick vectors were present on livestock in
      rural areas throughout the year, and first seroconversion occurred at any age,
      although the majority of calves seroconverted between 1 and 10 months old, sheep
      by 11 months, and goats by 7 months. All the cattle in the study became
      seropositive by 20 months of age, except one animal which subsequently died of
      heartwater. Following seroconversion, 25% of bovine sera tested negative in the
      PC-ELISA. Just over half the sheep in the survey seroconverted before or during
      the study period; following seroconversion, less than 3% of ovine sera became PC
      ELISA negative. About a quarter of the goats seroconverted, and 34% of their post
      seroconversion sera tested negative in the PC-ELISA. Overall, the serology
      indicated that virtually all cattle on the survey farms were exposed to E.
      ruminantium without suffering disease, but that a substantial proportion of sheep
      and goats escaped exposure and thus formed a susceptible population. E.
      ruminantium was detected in brains of 14, 36 and 4% of cattle, sheep and goats
      submitted for post mortem at the Accra Veterinary Laboratory, indicating that
      sheep were most at risk from heartwater disease.

PMID- 15145497
TI  - Multiple genetic typing of Salmonella Enteritidis phage-types 4, 6, 7, 8 and 13a
      isolates from animals and humans in the UK.
AB  - Salmonella enterica serovar Enteritidis is a common cause of salmonellosis in
      people in the UK. This study aimed to assess the degree of genetic diversity
      among animal and human isolates from UK, Wales and northern Ireland. A total of
      250 isolates from humans (n = 59) and animals or their environment (n = 191),
      belonging to the most common phage-types, were fingerprinted by a combination of
      PFGE, PS ribotyping and plasmid profiling. The different techniques identified
      different degrees of polymorphism (PS ribotyping (52 types) > PFGE (22 types) >
      plasmid profiling (17 types)). A prevalent genomic clone, as well as a variety of
      less frequent clones are present for each of the phage-types. In most cases, the
      prevalent clones appeared within isolates from several animal species and from
      several geographical locations. The percentage of sporadic clones found in animal
      and human populations were very similar. There was not clear evidence of a higher
      degree of diversity for human or animal isolates. Some clones were found to be
      present in both human and animal.

PMID- 15145498
TI  - Newly developed primers for the detection of Mycobacterium avium subspecies
      paratuberculosis.
AB  - Recent publications reported the existence of IS900 like sequences in
      mycobacteria different from Mycobacterium avium subspecies paratuberculosis
      (Map). The primers used for IS900 detection of Map have amplified these sequences
      causing false positive results. In this study, we have developed two new PCR
      assays for the detection of Map. The first assay is based on the IS900 sequence
      using primers different from the ones previously reported, the second assay on
      the f57 sequence. The specificity of the tests was checked by analysis of 190
      mycobacterial isolates (74 Map and 116 non-Map isolates). All Map strains were
      positive and all non-Map strains were negative. Serial dilutions of Map bacteria
      were used to assess the sensitivity of the assays. We achieved a sensitivity of
      1CFU per PCR for both assays. In addition, a PCR-simulating computer programme
      was used to evaluate the specificity of the new IS900 primers. The combination of
      the two PCR assays has proven to be useful for the identification of Map but
      validation on a large range of clinical samples still needs to be done.

PMID- 15145499
TI  - Comparison of pulsed field gel electrophoresis and repetitive sequence polymerase
      chain reaction as genotyping methods for detection of genetic diversity and
      inferring transmission of Salmonella.
AB  - Pulsed field gel electrophoresis (PFGE) using restriction enzymes AvrII, SpeI,
      and XbaI, and repetitive sequence polymerase chain reaction (Rep-PCR) using BOX,
      ERIC, and REP primers, were compared with respect to their ability to detect
      genetic differences among 68 Salmonella isolates from nine Illinois swine farms.
      Both genotyping methods had high reproducibility of fragment numbers
      (reliability>0.9) and sizes (reliability>0.85), and sizes [Formula: see text],
      and produced approximately the same number of DNA fragments, but Rep-PCR fragment
      profiles had considerably greater variation. Genetic distances between isolates
      were calculated from fragment size matching. There was good agreement between the
      genetic distance matrices for the composite (3-enzyme and 3-primer) methods
      (Mantel's r=0.83). PFGE detected slightly greater variation in genetic distances
      among isolates, but failed to differentiate seven pairs of isolates, three of
      which were sampled at least 1 month apart and therefore unlikely to be truly
      identical genetically. In contrast, Rep-PCR identified no isolates as genetically
      identical. In cluster analyses based on genetic distances, there were moderate
      differences between PFGE and Rep-PCR (about 2/3 agreement in tight cluster
      membership). Both PFGE and Rep-PCR were able to differentiate isolates of the
      same serotype. However, some serotypes (Agona, Anatum, Derby, Infantis,
      Worthington) were distributed across clusters. There was less agreement between
      individual primer/enzyme and composite results for Rep-PCR than for PFGE. This
      greater independence of results for individual primers for Rep-PCR accounted in
      part for the greater discriminative ability of the composite method. Both
      composite methods indicated that most Salmonella transmission occurred within a
      farm and that there was no preference for transmission between specific
      ecological compartments. Given the equally high reliability of both genotyping
      methods, the greater discriminative ability of Rep-PCR recommends it as the
      preferred method for precise detection of transmission links.

PMID- 15145501
TI  - Identification of Ehrlichia ruminantium (Gardel strain) IFN-gamma inducing
      proteins after vaccination with a killed vaccine.
AB  - IFN-gamma is considered as a key factor in protection against heartwater of
      ruminants, caused by the obligate intracellular bacterium Ehrlichia ruminantium.
      In this study, a better definition of the molecular masses of IFN-gamma inducing
      proteins of the Gardel strain of E. ruminantium was obtained by the use of
      continuous flow electrophoresis (CFE) and sensitized polyclonal lymphocytes. Out
      of 15 E. ruminantium CFE fractions tested within the 14-39 kDa region, eight were
      commonly reacted to by all goats. Interestingly, half of these fractions fall
      within the 23-29 kDa region, shown previously to contain polymorphic B-cell
      epitopes. Thus, the results suggest that this region also contains T-cell
      epitopes potentially involved in protection. Also, several proteins were found to
      be more immunogenic than the serologically immunodominant MAP1 protein. Finally,
      high activity within the 15-19 kDa region was observed, which confirms previous
      work done with CD4+ T-cell lines obtained from cattle immunized with a South
      African strain of E. ruminantium. The proteins falling within the molecular
      weight ranges defined in this study may have potential as vaccine antigens.

PMID- 15145502
TI  - Inhibition of adhesion of F18+ Escherichia coli to piglet intestinal villous
      enterocytes by monoclonal antibody against blood group H-2 antigen.
AB  - Enterotoxigenic and verotoxigenic F18+ Escherichia coli colonising the pig small
      intestine, adhere to receptors on intestinal villous enterocytes by F18 fimbriae.
      The aim of the present study was to define the F18R nature. The knowledge on the
      nature of this receptor could be important for the development of receptor-based
      treatments against F18+ E. coli-induced disease. The adhesion of F18+ E. coli to
      pig intestinal villous enterocytes was analysed in an in vitro assay. The
      adhesion of F18+ E. coli but not of F4ac+ E. coli was strongly inhibited by
      monoclonal antibodies (mAb) with blood group H-2 specificity. Conversely, blood
      group H-1 specific mAb could not inhibit the adhesion of F18+ E. coli nor F4ac+
      E. coli. Moreover, the blood group H-2 trisaccharide strongly inhibited the
      adhesion of F18+ E. coli, but only partially the adhesion of F4ac+ E. coli. These
      data demonstrate that the F18 receptor contains the blood group antigen H-2
      (alpha-fuc-(1-2)-beta-Gal-(1-4)-GlcNAc) as major carbohydrate.

PMID- 15145500
TI  - Antibody response and antigen-specific gamma-interferon profiles of vaccinated
      and unvaccinated pregnant sheep experimentally infected with Brucella melitensis.
AB  - It is well known that the immune response in sheep against Brucella melitensis is
      subject to individual variation, depending on diverse factors. It bears asking
      whether these factors (e.g. clinical disease, active infection, state of previous
      immunity), when affecting a group, can cause variation in the performance of
      different diagnostic tests. To clarify some of the circumstances in which this
      immune response can vary, we examine the immune-response profile of sheep
      protected against the clinical disease by prior vaccination with strain Rev. 1 in
      comparison with the profile of unprotected females showing the classical
      brucellosis symptoms. An experimental infection was provoked at midpregnancy
      under controlled conditions of both non-vaccinated (n=7) and previously Rev.1
      vaccinated ewes (n=5). Their immune response was monitored from 7 to 9 weeks
      before abortion or normal birth to 30 weeks afterwards. Antibody response was
      assessed by classical tests (Rose Bengal test, complement fixation test (CFT)) in
      comparison with other diagnostic tests (indirect ELISA (iELISA), competitive
      ELISA (cELISA), fluorescence polarization assay (FPA), immunocapture test (ICT)).
      In addition, the cell-mediated immune response was indirectly evaluated by the in
      vitro antigen-specific release of gamma-interferon. The antibody levels and
      antigen-specific gamma-IFN profile of the non-vaccinated ewes having the disease
      and excreting the pathogen was notably high and differed significantly (P<0.05 or
      P<0.01) from those of vaccinated ewes that neither contracted brucellosis nor
      excreted the pathogen. In general, all the tests detect the infection in the non
      vaccinated ewes with substantial effectiveness. It can be concluded that the high
      levels of circulating antibodies and of antigen-specific gamma-IFN are related to
      active Brucella infection. Similarly, the state of protection against the
      disease, but not necessarily against infection, due to a previous immunization
      with the Rev. 1 vaccination, appears to be responsible for a low level of
      detectable immune response. Nevertheless, the design of the study limits
      conclusions to pregnant ewes and cannot be extrapolated to non-pregnant ewes or
      rams. Likewise, the study provides no information on animals which are carriers
      of B. melitensis.

PMID- 15145503
TI  - Detection of mutations in the gyrA gene and class I integron from quinolone
      resistant Salmonella enterica serovar Choleraesuis isolates in Taiwan.
AB  - The quinolone resistance-determining regions (QRDRs) of the gyrA gene of
      quinolone-resistant Salmonella enterica serovar Choleraesuis isolates were
      sequenced. Four types of point mutation, Ser-83-to-Phe (TCC --> TTc), Ser-83-to
      Tyr (TCC --> TAC), Asp-87-to-Gly (GAC --> GGC), and Asp-87-to-Asn (GAC --> AAC),
      were found. PCR-RFLP and MAS-touch down PCR were performed on fifty swine
      clinical isolates of S. enterica serovar Choleraesuis (NalR) collected during
      1997-2002. The analysis indicated seven isolates with point mutations in codon
      83, 13 with point mutations in codon 87, and 30 with double mutations in both
      codons 83 and 87. The MICs of enrofloxacin of the isolates with a single mutation
      in codon 83 or 87 were <2microg/ml, while the MICs of the isolates with double
      mutations in both codon 83 and 87 ranged from 2 to 64microg/ml. A class I
      integron comprised of dhfr, orfF and aad2 was also identified in both human and
      swine S. enterica serovar Choleraesuis isolates. These results indicate that PCR
      RFLP and MAS-touchdown PCR assays can be used for surveillance of gyrA gene
      mutations, which are important for fluoroquinolone resistance in Salmonella.
      Isolates with double mutations in gyrA codons 83 and 87 are the major type of
      quinolone-resistant Salmonella isolated from swine in Taiwan. A surveillance
      system may be applied to the swine industry to monitor the emergence of
      fluoroquinolone and/or multi-drug-resistant S. enterica serovar Choleraesuis in
      Taiwan.

PMID- 15145504
TI  - Efficacy of vaccines against bacterial diseases in swine: what can we expect?
AB  - This paper discusses what can be expected with regard to efficacy of
      antibacterial vaccines used in swine, based on the present knowledge of pathogen
      host interactions. First, vaccination against bacteria that mainly cause disease
      by production of exotoxins is considered. Vaccines containing the inactivated
      toxin or a non-toxic but antigenic recombinant protein derived from the exotoxin
      can be expected to provide protection against disease. The degree of protection
      induced by such vaccines varies, however, depending amongst other things on the
      pathogenesis of the disease. Vaccination against clostridial infections,
      Actinobacillus pleuropneumoniae infections, progressive atrophic rhinitis and
      enterotoxigenic Escherichia coli, is considered. The second part of the article
      deals with vaccination against extracellular bacteria. Protection against these
      bacteria is generally mediated by antibodies against their surface antigens and
      certain secreted antigens, but cellular immunity may also play a role. Efficacy
      of vaccines against swine erysipelas, Streptococcus suis infections, Mycoplasma
      hyopneumoniae infections and swine dysentery is discussed. Finally, vaccination
      against facultatively intracellular bacteria is considered. For protection
      against these bacteria cell-mediated immunity plays an important role, but
      antibodies may also be involved. It is generally accepted that live-attenuated
      vaccines are more suitable for induction of cell-mediated immunity than
      inactivated vaccines, although this also depends on the adjuvant used in the
      vaccine. As an example, vaccination against Salmonella enterica serotype
      Typhimurium is discussed.

PMID- 15145505
TI  - Detection of genomic DNA of the crayfish plague fungus Aphanomyces astaci
      (Oomycete) in clinical samples by PCR.
AB  - A diagnostic procedure, based on a polymerase chain reaction method (PCR) was
      developed to detect infection of crayfish with the Oomycete Aphanomyces astaci. A
      set of oligonucleotide primers was designed to specifically amplify A. astaci DNA
      in the ITS region surrounding the 5.8S rDNA gene. The PCR amplifies a 115bp
      amplicon. The specificity of the primers was demonstrated by testing on 27 A.
      astaci strains and against 20 non-A. astaci Oomycetes and 5 fungal species. Most
      of the non-A. astaci Oomycete or fungal species included in the study are either
      known parasites of freshwater crayfish cuticle or can be found in their natural
      environment. Specificity was also tested against crayfish tissue and some known
      parasites and bacteria infecting crayfish. A protocol for the extraction of A.
      astaci DNA from infected crayfish tissue was developed. The optimised method
      allows the detection of two genome equivalents of purified A. astaci genomic DNA.
      The method was tested on noble crayfish (Astacus astacus), artificially infected
      with A. astaci. Detection of A. astaci was possible at the very first time of
      sampling, which was 2 days after the beginning of spore exposure.

PMID- 15145506
TI  - Differential clustering of Mycoplasma mycoides subsp. mycoides SC strains by PCR
      REA of the bgl locus.
AB  - In order to develop a specific tool differentiating the African field strains of
      Mycoplasma mycoides subsp. mycoides SC from other potentially less virulent
      strains, including the vaccine strains, we have developed a PCR followed by a
      restriction enzyme analysis (PCR-REA). This approach also differentiates the
      African field strains from the Australian strains and the type strain PG1. The
      genomic marker detected by the PCR-REA is based on a single nucleotide change in
      the bgl gene that codes for 6-phospho-beta-glucosidase (Bgl), an enzyme that is
      involved in sugar metabolism.

PMID- 15145507
TI  - Aromatase inhibitors in the adjuvant setting: bringing the gold to a standard?
AB  - The death rate from breast cancer is falling rapidly in most developed countries
      due, at least in part, to the use of adjuvant endocrine therapy in women with
      endocrine responsive disease. In post-menopausal women tamoxifen has been the
      gold standard for nearly 20 years. More recently the aromatase inhibitors (AI)
      have become established in the management of advanced breast cancer and are being
      evaluated in the adjuvant setting in trials that include tens of thousands of
      women. Recently, data have emerged that provide increasingly strong evidence
      supporting the use of AI in the adjuvant setting. Anastrozole as initial adjuvant
      endocrine treatment has shown superiority over tamoxifen in terms of disease free
      survival, and impressive reductions in the risk of recurrence have been
      demonstrated in trials evaluating the switch from tamoxifen to an AI, either
      letrozole after 5 or exemestane after 2-3 years of tamoxifen respectively. The
      data from these recent publications, and the potential impact on routine care of
      women with post-menopausal breast cancer is discussed.

PMID- 15145508
TI  - Taxanes in elderly breast cancer patients.
AB  - Breast cancer in elderly patients (70+) is a major health problem that will only
      increase in the future. Besides adequate local treatment and hormone therapy,
      there can be an indication for chemotherapy in this patient group. Due to
      concerns of excessive toxicity, there is often a defeatist attitude towards
      chemotherapy in elderly patients. As taxanes are considered to be the most
      effective drugs in breast cancer, and as the weekly regimens seem at least as
      effective as the 3-weekly regimens but with less toxicity, these weekly regimens
      are very attractive for elderly breast cancer patients. Many different doses have
      been used for the weekly taxane regimens in phase II trials. Although large
      comparative studies are lacking, pharmacological studies are suggestive for a
      decreased clearance of both paclitaxel and docetaxel in elderly patients compared
      to non-elderly patients. It seems therefore safe to use the lower range of
      proposed doses of the weekly regimens until further data provide stronger
      evidence for optimal dosing in elderly patients. A dose of paclitaxel 80
      mg/m(2)/week and docetaxel 36 mg/m(2)/week seems tolerable for elderly patients
      without excessive toxicity and with impressive response rates. The dose limiting
      toxicity for 3-weekly taxanes, severe neutropaenia, is generally very limited in
      weekly regimens, also in the elderly or frail patients. However, neuropathy
      (paclitaxel) or fatigue and fluid retention (docetaxel) can be troublesome, and
      eventually require dose modifications. In general however, weekly taxanes are a
      reasonable option for older patients with metastatic breast cancer.

PMID- 15145509
TI  - Systemic chemotherapy for patients with bladder cancer--current controversies and
      future directions.
AB  - Many localised, superficial bladder cancers can be effectively controlled.
      However, disease which has spread to nodes outside the pelvis or to distant
      organs is generally incurable and systemic therapies, rather than surgery, are
      appropriate. Combination chemotherapy based around established cytotoxic drugs
      such as cisplatin has proven benefit in palliating symptoms and prolonging
      survival in responsive patients with advanced disease. Combination chemotherapies
      which include newer cytotoxic drugs such as gemcitabine provide the potential for
      equivalent efficacy with less toxicity than established regimens. Between the
      extremes of superficial and advanced disease, muscle-invasive bladder cancers
      have traditionally been treated, with curative intent, by radical surgery or
      radiotherapy. However, newly published data suggest, for the first time, genuine
      survival benefits from peri-operative chemotherapy. This article reviews the
      evidence for cisplatin-based chemotherapy in advanced disease, assesses the
      potential benefits of newer cytotoxic drugs, discusses the latest evidence
      pertaining to peri-operative chemotherapy in muscle-invasive disease, and looks
      forward to potential new biological agents in the systemic therapy of bladder
      cancer.

PMID- 15145510
TI  - Treatment of small cell lung cancer in the elderly based on a critical literature
      review of clinical trials.
AB  - At diagnosis, 25-40% of patients with small cell lung cancer (SCLC) are 70 years
      of age or older, and many of them have been undertreated because of fear of
      excessive toxicity associated with chemotherapy. Papers retrieved by a Medline
      search using the key words "elderly or older" and "small cell lung cancer" and by
      a manual search were classified into the three types: (1) case-series studies,
      (2) subgroup analyses of phase II and phase III trials by age, and (3)
      prospective clinical trials in the elderly. Treatment regimens, delivery,
      toxicity, antitumor activity, and patient survival were reviewed in elderly
      patients with good and poor general condition. The standard chemotherapy regimens
      for the general population could be applied to elderly patients in good general
      condition (performance status of 0-1, normal organ function, and no comorbidity),
      but etoposide and carboplatin regimen with dose modification was frequently used
      for unselected elderly patients. A combination of full-dose thoracic radiotherapy
      and chemotherapy was the treatment of choice for limited SCLC in the elderly.
      Full cycles of chemotherapy were tolerable by 80% of the elderly patients with
      good general condition, but two cycles may be optimal for unselected elderly
      patients. Although the evidence levels based on clinical trials available today
      are low, these results are helpful for clinical practice and future clinical
      trials for elderly patients with SCLC.

PMID- 15145511
TI  - Radiotherapy-induced thyroid disorders.
AB  - Despite their specific functional consequences, radiotherapy-induced thyroid
      abnormalities remain under-estimated and underreported. These sequelae may
      include primary or central hypothyroidism, thyroiditis, Graves' disease,
      euthyroid Graves' ophthalmopathy, benign adenomas, multinodular goitre and
      radiation-induced thyroid carcinoma. Primary hypothyroidism, the most common
      radiation-induced thyroid dysfunction, affects 20-30% of patients administered
      following curative radiotherapy to the neck region, with approximately half of
      the events occurring within the first 5 years after therapy. The relative risk of
      radiation-induced cancer (mainly well-differentiated tumours) is 15-53-fold
      higher than in non-irradiated population. The aetiology of radiation-induced
      thyroid injury includes vascular damage, parenchymal cell damage and auto-immune
      reactions. Total radiotherapy dose, irradiated volume of the thyroid gland, and
      the extent of prior thyroid resection are among the most important factors
      associated with the risk of hypothyroidism. The contribution of other treatment
      modalities (chemotherapy, endocrine therapy) as well as patient- and tumour
      related factors is less clear. Reduction in radiation dose to the thyroid gland
      and hypothalamic/pituitary complex should be attempted whenever possible. New
      radiotherapy techniques, such as stereotactic radiosurgery, three-dimensional
      conformal irradiation, intensity modulated radiotherapy and proton therapy allow
      generally better dose distribution with lower dose to the non-target organs. The
      diagnostic approach to thyroid radiation injury includes baseline thyroid
      function assays in all patients undergoing thyroid or parasellar irradiation.
      Recommended follow-up procedures include at least annual evaluation with a
      history for symptoms of thyroid dysfunction, clinical examination, and
      measurement of thyroid hormones and thyrotropin. Management of overt
      hypothyroidism is based on hormone replacement therapy. Thyroid hormone therapy
      is also recommended in cases of subclinical hypothyroidism. Treatment of other
      radiation-induced thyroid disorders (thyroiditis, Graves' disease, thyroid
      cancer) is similar to that employed in spontaneously occurring conditions.
      Further improvements in radiotherapy techniques and progress in endocrine
      diagnostics and therapy may allow better prevention and management of radiation
      related thyroid injury.

PMID- 15145512
TI  - Adding Gram-positive prophylaxis to fluoroquinolone regimens reduces
      streptococcal bacteraemias, but prophylaxis remains controversial.

PMID- 15145514
TI  - No difference between pamidronate disodium and placebo in relieving bone pain in
      men with advanced prostate cancer.

PMID- 15145513
TI  - Addition of prophylactic gastrojejunostomy to hepaticojejunostomy significantly
      reduces gastric outlet obstruction in people with unresectable periampullary
      cancer.

PMID- 15145515
TI  - Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast
      to sporadic papillary carcinomas.
AB  - Point mutations of the BRAF gene have been recently described with high
      prevalence in papillary thyroid carcinomas. However, this molecular alteration
      has not been studied in radiation-induced thyroid tumors. We analyzed the
      prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post
      Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas.
      Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point
      mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary
      carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF
      mutations and 20% RET/PTC rearrangements. These results demonstrate a significant
      difference in the molecular genetic profile of sporadic and radiation-induced
      thyroid tumors.

PMID- 15145516
TI  - Differential inhibition of fatty acid transport in tissue-isolated steroid
      receptor negative human breast cancer xenografts perfused in situ with isomers of
      conjugated linoleic acid.
AB  - In established rodent tumors and human cancer cell lines, conjugated dienoic
      isomers of linoleic acid (CLA) suppress the growth-stimulating effects of
      linoleic acid (LA) and its metabolism to the mitogenic agent, 13
      hydroxyoctadecadienoic acid (13-HODE). Here, we compared the effects of three CLA
      isomers on LA uptake and metabolism, and growth in human breast xenografts
      perfused in situ in female nude rats. The results demonstrated that two CLA
      isomers [10t, 12c-CLA>9t, 11t-CLA] caused a dose-dependent inhibition of LA
      uptake, cAMP content, 13-HODE formation, Erk 1/2 activity, and [(3)H]thymidine
      incorporation into tumor DNA; 9c, 11t-CLA showed no effect. The inhibitory effect
      is reversible with either pertussis toxin (PTX) or 8-Br-cAMP suggesting that CLA
      isomers differentially inhibit LA uptake and metabolism and cell proliferation in
      human breast cancer in vivo via a receptor-mediated, PTX-sensitive pathway.

PMID- 15145517
TI  - Effects of sucrose and cornstarch on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)
      induced colon and liver carcinogenesis in F344 rats.
AB  - The purpose of the present study was to compare the effect of sucrose and
      cornstarch on colon and liver carcinogenesis induced by 0.02% of the food-borne
      carcinogen 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) in the feed. Male F344
      rats were allocated to four groups. Two groups were fed diets high in either
      cornstarch (68%) or sucrose (34% sucrose/34% cornstarch) and were initiated with
      IQ. The remaining two groups received the same two diets but did not receive any
      IQ. In both liver and colon, administration of IQ resulted in a higher level of
      DNA adducts. In animals not dosed with IQ, sucrose increased the adduct level in
      both organs but to a lower level than IQ. However, simultaneous administration of
      IQ and sucrose did not further increase the adduct level. Both IQ and sucrose
      increased the expression of the DNA-repair enzyme ERCC1 in the liver. In the
      colon, the number of large and medium aberrant crypt foci (ACF) of the group fed
      IQ and cornstarch was significantly higher than that in the other groups. There
      was no statistically significant difference in any tumour incidence in IQ dosed
      animals fed either cornstarch or sucrose. In conclusion, no difference in effect
      on liver carcinogenesis was seen between sucrose and cornstarch-based diets,
      however, the number of tumours per animal tended to be slightly higher in the
      rats fed cornstarch (P = 0.08). Cornstarch enhanced ACF development induced by IQ
      when compared to sucrose whereas due to a low intestinal tumour incidence no
      correlation to diet and tumour incidence could be established.

PMID- 15145518
TI  - Effect of linoleic acid on proliferation and gene expression in the breast cancer
      cell line T47D.
AB  - Human and animal studies have linked n-6 polyunsaturated fatty acids with mammary
      carcinogenesis. We investigated the cellular and molecular effects of linoleic
      acid on the human breast cancer cell line T47D. Linoleic acid had a stimulatory
      effect on the growth of T47D cells, associated with an increase in the proportion
      of cells in the S phase of the cell cycle. Microarray, functional group and
      quantitative PCR analyses indicate that linoleic acid may affect T47D cell growth
      by modulation of the estrogen receptor (ERalpha), the G13alpha G protein, and p38
      MAP kinase gene expression as well genes involved in RNA transcription and cell
      cycle regulation.

PMID- 15145519
TI  - HPV18 E6 and E7 genes affect cell cycle, pRB and p53 of cervical tumor cells and
      represent prominent candidates for intervention by use peptide nucleic acids
      (PNAs).
AB  - Approximately 100% of cervical carcinomas are causally linked to infections with
      high-risk human papillomaviruses (HPVs), whose oncogenicity has been assigned to
      the continued expression of two early viral genes, E6 and E7. Reversal of the
      transformed phenotype by inhibiting E6/E7 gene expression therefore provides a
      suitable goal for tumor therapy. We established an application controlling the
      E6/E7 expression of the HPV type 18, by using viral gene directed peptide nucleic
      acids (PNAs). One consequence was the complete change in growth to a stagnated
      behavior of the HPV 18 positive HeLa-S cells. With flow cytometry, we
      investigated changes in the cell cycle and expression of the pRB (retinoblastoma)
      and p53 genes acting as antagonists to E6 and E7. We realized that application of
      PNAs via intracellular cleavable conjugated peptide carriers mediates specific
      inhibitory effects and we showed that the combined E6/E7-directed PNA-application
      mediated a clear morphological change from suspension to adherend state and the
      cells stopped growth. These data could demonstrate a promising approach for
      development of new 'anti-gene therapeutics' against papillomavirus-induced human
      cancers.

PMID- 15145520
TI  - The inhibition of tumor growth by triplex-forming oligonucleotides.
AB  - We have previously shown that oligonucleotides designed to bind in triplex
      fashion to a specific p53 binding site homology inhibit the proliferation of
      colon cancer cells in vitro. The present study was designed to extend these
      observations in an in vivo model. HCT 116 human colon carcinoma cells were
      injected subcutaneously into Ncr nude mice and tumors formed at one to two weeks.
      Tumors were injected daily for 14 days with either triplex forming
      oligonucleotide (Hoog 1), a scrambled Hoog 1 oligonucleotide (Hoog3) as control,
      or vehicle. Tumor size was measured twice weekly. Active triplex forming
      oligonucleotide (Hoog1) reduced tumor size in comparison to either control
      oligonucleotide (Hoog3) or vehicle. Tumor sizes in the three groups were
      significantly different (P < 0.001). Student Newman Keuls test shows
      statistically significant differences between the experimental group and each of
      the control and vehicle groups (P < 0.05). A triplex forming oligonucleotide
      directed at a p53 consensus binding site reduces tumor growth suggesting a novel
      method of tumor inhibition.

PMID- 15145521
TI  - Tamoxifen induces the expression of maspin through estrogen receptor-alpha.
AB  - Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays
      an important role in inhibiting tumor growth, invasion and metastasis. Maspin
      expression is down regulated at transcription level in primary and metastatic
      breast tumor cells. Previous studies on hormonal regulation of maspin prompt us
      to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor
      function by up regulating maspin gene expression. For this purpose, we first
      tested whether maspin promoter could be activated in normal and several breast
      tumor cells. We then carried out a series of promoter analysis in which estrogen
      receptors and TAM were reconstituted in an in vitro cell culture system. Here we
      report our new finding that tumor suppresser gene maspin is one of the TAM target
      genes. TAM induces a maspin/luciferase reporter in cell culture and this
      induction requires the presence of (estrogen receptor alpha) ERalpha but not
      estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis
      showed that the cis element(s) within a region between -90and+87 bp but not the
      HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound
      ERalpha may directly control maspin gene expression through the interaction with
      cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal
      A/B motif (AF-1) was critical for maspin basal level transcription activation. An
      ERalpha mutant with point mutations at DNA binding domain abolished estrogen
      induction of an ERE-luciferase reporter but was still active in activating maspin
      promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction.
      Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region
      (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting
      that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha
      to the maspin promoter region. This finding indicates that one of the pathways
      for cancer prevention and tumor inhibition by TAM is mediated through the
      activation of tumor suppressor gene maspin in breast cancer.

PMID- 15145522
TI  - Dipeptidase 1: a candidate tumor-specific molecular marker in colorectal
      carcinoma.
AB  - The aim of this study was to identify tumor-specific markers for the detection of
      rare disseminated colorectal tumor cells in peripheral venous blood and in intra
      peritoneal saline lavage samples collected before and after resection of
      colorectal tumors. Using cDNA micro-array screening, we found dipeptidase 1
      (DPEP1) to be highly expressed in colon tumors compared to matched normal mucosa.
      Relative reverse transcriptase (RT)-PCR showed that DPEP1 was over-expressed by
      >/=2 fold in colon tumor compared to normal colonic mucosal tissue in 56/68 (82%)
      patients. Using immunobead RT-PCR, a technique that first enriches for epithelial
      cells, we found DPEP1 positive cells in intra-peritoneal lavage and venous blood
      samples from 15/38 (39%) colorectal cancer cases. This is the first report of
      DPEP1 as a marker for disseminated colon tumor cells.

PMID- 15145523
TI  - Molecular cloning and characterization of LCRG1 a novel gene localized to the
      tumor suppressor locus D17S800-D17S930.
AB  - Laryngeal carcinoma (LC) is the most commonly diagnosed malignancy and recently
      the incidence of this disease has increased. By means of the mRNA differential
      display method we identified a cDNA, Laryngeal carcinoma related gene 1 (LCRG1)
      which has significantly reduced expression in 40% (12/30) of primary LCs and in 6
      of 10 various cancer cell lines. Northern Blot analysis showed that LCRG1 was
      expressed more abundantly in human heart, pancreas, skeletal muscle, and in
      murine testis, liver, brain and heart than in other tissues. The cDNA sequence of
      this gene is identical to part of the sequence of PAC HCIT75G16 clone (GenBank
      accession No. AC003042) from the chromosome band 17q12-21.1 which is one of the
      most common loss of heterozygosity (LOH) regions involved in LC, prostate cancer,
      etc. This gene is composed of six exons and spans about 60 kb of genomic DNA with
      a 3.4 kb mature transcript. The alignment of this gene with STS markers localized
      the gene to the previously identified tumor-suppressor locus D17S800-D17S930. The
      putative protein encoded by this gene is 288 amino acid with one potential site
      for phosphorylation by casein kinase II and no significant homology to any known
      proteins in the public databases. The primary tumor suppressive functions
      (proliferation rate,soft agar growth and tumor formation) were observed in a LC
      cell line (Hep-2) by lipofectin transfection. Together these data strongly
      suggest a potential role of LCRG1 contributing to the development of LC.

PMID- 15145524
TI  - Conjugated linoleic acid modulation of cell membrane in leukemia cells.
AB  - This study compared the cellular uptake of pure conjugated linoleic acid isomers
      (CLA(9c,11t) and CLA(9c,11c)) to linoleic acid (LA) and their effects on
      polyunsaturated fatty acid (PUFA) synthesis, its metabolism into conjugated long
      chain fatty acids (FAs) by desaturation and chain-elongation as well as cell
      proliferation and the associated anticarcinogenic effects on various human
      leukemia cell lines (K562, REH, CCRF-CEM and U937 cells). Furthermore, selective
      effects of this individual isomers of CLA on desaturation steps involved in the
      biosynthesis of PUFAs associated with cell growth were investigated. CLA isomers
      supplemented in the culture medium was readily incorporated and esterified into
      phospholipids (PLs) in the four cell lines in a concentration- and time-dependent
      manner. The incorporation of the specific CLA isomers in PLs was similar to LA.
      All four incubating leukemia cells (40 microM CLA for 48 h) showed very high
      cellular CLA content in PLs (range: 32-63 g FA/100 g total phospholipid fatty
      acid) affected by the nature of CLA and the cell type. Supplementation with CLA
      or LA altered also cell membrane composition by n-6 PUFA synthesis. Accordingly,
      CLA metabolism interferes with LA metabolism. We were able to show that CLA
      isomers are converted by the leukemia cells of the same metabolic pathway into
      conjugated diene fatty acids (CDFAs) as LA into non-conjugated PUFAs. In this
      view, the gas chromatography-flame ionization detector detection of major CDFAs
      (CD-18:3, CD-20:2 and CD-20:3) in cell membrane of CLA-treated cultures resulted
      from successive Delta6-desaturation, elongation and Delta5-desaturation of CLA
      isomers. However, in comparison to LA, relatively lower amounts of elongation
      and/or desaturation metabolites were detected for CLA(9c,11t), and only minor
      amounts or trace CDFAs were observed for CLA(9c,11c). Furthermore, CLA(9c,11t)
      revealed only very low levels of CD-20:4 FA and no CLA(9c,11c)-conversion could
      be detected. The metabolization of CLA indicated that CLA(9c,11c)<CLA(9c,11t)
      were a poorer substrates in compared to LA for the Delta5,6
      desaturation/elongation in REH, CCRF-CEM and U937 cells or for the Delta5
      desaturation/elongation in the K562 cells. CLA(9c,11t) suppresses Delta6
      desaturation in CCRF-CEM, REH, and U937 cells (43.5, 54.6 and 58.8% Delta6
      inhibition, respectively) and as well Delta9-desaturation in all four cell lines
      (Delta9-inhibition; 47.1, 33.9, 29.8 and 25.9% for CCRF-CEM, REH, K562 and U937
      cells, respectively). However, CLA(9c,11c) does not inhibit or only slightly
      affected these desaturations. CLA(9c,11t) isomer was found as an Delta6
      desaturase inhibitor with a dose-dependent relationship between inhibition of
      Delta6-desaturase activity and decreases in cell growth. The growth inhibitory
      effects of CLA (with 30-120 microM) on leukemia cells were dependent upon the
      type and concentration of CLA isomers present. CLA-supplemented cells with low
      concentrations (<60 microM) were not sufficient to impair cell proliferation.
      Nevertheless, higher amounts of CLAs (>60 microM) had the CLA type dependent
      antiproliferative effects. Thus, the 9cis,11trans- and the 9cis,11cis-CLA isomers
      regulate cell growth and survival in different leukemia cell types through their
      existence alone and/or by their inhibitory effects of desaturase activity.

PMID- 15145525
TI  - CD9 expression is not a prognostic factor in human osteosarcoma.
AB  - CD 9, also known as Motility-Related Protein-1 (MRP-1), is a member of the
      transmembrane four superfamily and plays a crucial role in cell adhesion,
      motility and signalling events. Downregulation of CD 9 has been reported to be
      associated with tumour progression, metastasis and clinical outcome in various
      kinds of solid tumours. Although prognosis of osteosarcoma has been improved by
      chemotherapy during the last decades, the problem of non-responders remains. At
      the present time prognostic factors at diagnosis have not been clearly
      identified. Furthermore, there is a need for markers that predict the response to
      chemotherapy at the time of biopsy, allowing stratification of osteosarcoma
      patients. In this study we investigated the effect of CD9 expression on the
      response to chemotherapy and survival in osteosarcoma. The expression of CD9 was
      examined immunohistochemically in 52 patients with high grade osteosarcoma and
      the results were correlated with histologic response to chemotherapy, 5 year
      disease free and 5 year overall survival. In patients with osteosarcoma 22 of 52
      cases (42%) were positive for CD 9 expression, the rest were negative. CD 9
      expression status showed no statistically significant correlation with response
      to chemotherapy; 41% had a poor response and 59% a good response in the CD9
      positive group. In the CD9 negative group 57% had a good and 47% had a bad
      response. No significant difference was found when comparing disease free
      survival (58.9% in CD9 positive- versus 69.3% in CD9 negative tumours; P = 0.99)
      and overall survival of patients (54.0% in CD9 positive- versus 58.1% in CD9
      negative tumours; P = 0.90) with CD9 expressing tumours to those with reduced CD9
      expression. In conclusion our findings suggest that in contrast to solid tumours,
      CD9 is unlikely to provide any additional prognostic information for clinical
      purposes in osteosarcoma patients.

PMID- 15145526
TI  - Increased expression and altered location of annexin IV in renal clear cell
      carcinoma: a possible role in tumour dissemination.
AB  - The proteome of renal cell carcinoma and non-neoplastic kidney tissue was
      analysed from 12 patients by two-dimensional polyacrylamide gel electrophoresis
      to search for differentially expressed proteins in the tumour. Annexin IV was
      identified to be up-regulated in tumour cells. These patients and further 11 were
      characterized by RT-PCR. We found an increased amount of annexin IV mRNA.
      Immunohistochemical analysis revealed an altered localization of annexin IV in
      tumour cells. Additionally we demonstrate that over-expressed annexin IV promotes
      cell migration in a carcinoma model system. From these results above it seems
      possible that annexin IV plays an important role in the morphological
      diversification and dissemination of the clear cell renal cell carcinoma.

PMID- 15145527
TI  - p53 mutations are common in human papillomavirus type 38-positive non-melanoma
      skin cancers.
AB  - In cervical cells, the E6 protein of the oncogenic human papillomavirus (HPV)
      types inactivates p53, promoting its degradation. Consequently, mutations of the
      p53 gene are rarely seen in these cancers. Our recent data indicate that the
      cutaneous HPV38 is involved in skin carcinogenesis. In this study, we have
      determined the presence of HPV38 and the status of p53 gene in 32 non-melanoma
      skin cancers. We found that p53 gene is frequently mutated in HPV38-positive skin
      cancers and that HPV38 E6 does not promote p53 degradation. Thus, different
      mechanisms appear to be involved in the development of HPV-positive cervical and
      skin cancers.

PMID- 15145528
TI  - VAMP subfamilies identified by specific R-SNARE motifs.
AB  - In eukaryotes, interactions among the alpha-helical coiled-coil domains (CCDs) of
      soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs)
      play a pivotal role in mediating the fusion among vesicles and target membranes.
      Surface residues of such CCDs are major candidates to regulate the specificity of
      membrane fusion, as they may alter local charge at the interaction layers and
      surface of the fusion complex, possibly modulating its formation and/or the
      binding of non-SNARE regulatory factors. Based on alternate patterns in surface
      residues, we have identified two motifs which group vesicular SNAREs in two novel
      subfamilies: RG-SNAREs and RD-SNAREs. The RG-SNARE CCD is common to all members
      of the widely conserved family of long VAMPs or longins and to yeast and non
      neuronal VAMPs, possibly mediating "basic" fusion mechanisms; instead, only
      synaptobrevins from Bilateria share an RD-SNARE CCD, which is likely to mediate
      interactions to specific, yet unknown, regulatory factors and/or be the landmark
      of rapid fusion reactions like that mediating the release of neurotransmitters.

PMID- 15145529
TI  - Presynaptic AMPA receptors: more than just ion channels?
AB  - AMPA receptor ion channels are of paramount importance for postsynaptic
      excitation. Several reports demonstrate that AMPA receptors are present in the
      presynaptic compartment and point to a role of these receptors in the modulation
      of presynaptic function. We discuss here the possibility that not only ion influx
      through the receptor, but also biochemical cascades, activated by ligand binding
      and independent from ion flux, might contribute to AMPA mediated presynaptic
      modulation.

PMID- 15145530
TI  - Inherited retinal degenerations: therapeutic prospects.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal
      degenerative diseases, characterized by the progressive death of rod and cone
      photoreceptors. A tremendous genetic heterogeneity is associated with the RP
      phenotype. Most mutations affect rods selectively and, through an unknown
      pathway, cause the rod cells to die by apoptosis. Cones, on the other hand, are
      seldom directly affected by the identified mutations, and yet, in many cases,
      they degenerate secondarily to rods, which accounts for loss of central vision
      and complete blindness. Many animal models of RP are available and have led to a
      better understanding of the disease and to the development of therapeutic
      strategies aimed at curing the specific genetic disorder (gene therapy), slowing
      down or even stopping the process of photoreceptor degeneration (growth factors
      or calcium blockers applications, vitamin supplementation), preserving the cones
      implicated in the central visual function (identification of endogenous cone
      viability factors) or even replacing the lost cells (transplantation, use of stem
      or precursor cells). Still, many obstacles will need to be overcome before most
      of these strategies can be applied to humans. In this review, we describe the
      different therapeutic strategies being studied worldwide and report the latest
      results in this field.

PMID- 15145531
TI  - p24 proteins, intracellular trafficking, and behavior: Drosophila melanogaster
      provides insights and opportunities.
AB  - The p24 transmembrane proteins, also known as EMP24/GP25 (endomembrane protein
      precursor of 24kD (Schimmoller et al., 1995)) proteins, are components of coat
      protein (COP)-coated vesicles and are present in species as diverse as fungi,
      plants, flies, worms, and mammals, indicating that they have important conserved
      functions. Genetic, molecular, and biochemical characterization of these proteins
      and the loci that encode them has provided insights into their potential cellular
      roles, including postulated functions in vesicle cargo protein selection and
      sorting, COPI and COPII vesicle formation and budding, and quality control of
      proteins that mature through the secretory pathway. Recently, the first mutations
      in a Drosophila melanogaster p24 gene have been isolated and characterized. These
      alleles produce an interesting behavioral phenotype in females, affecting their
      ability to oviposit. This identification and mutant characterization of a p24
      locus in Drosophila will pave the way for a better understanding of cell-type
      specific functions and interactions among p24 proteins.

PMID- 15145533
TI  - Participation of the adhesive disc during karyokinesis in Giardia lamblia.
AB  - Evidence is presented for a potential involvement of the adhesive disc on the
      nucleus division in Giardia lamblia. The trophozoite mitotic nucleus was studied
      by transmission electron microscopy, freeze-fracture, freeze-substitution and
      also by immunofluorescence microscopy using anti-tubulin antibodies specific to
      spindle microtubules and Panotic staining. Prior to cell division the nucleus
      elongated and a displaced disc fragment, established contact with the nucleus. A
      progressive nucleus indentation was coincident with the concomitant presence of a
      disc fragment at the constricted region. One nucleus each time progressively
      divided until the karyokinesis was finished and two daughter-nuclei were
      observed. After the first karyokinesis a second karyokinesis takes place
      following the same procedure. When Giardia gets the four nuclei, cytokinesis
      occurs. Duplicated basal bodies were seen in between the first and the second
      karyokinesis. Immunofluorescence microscopy, using a panel of anti-tubulin
      antibodies, and electron microscopy of cells processed using microtubule
      stabilizer buffers, or cells fast-frozen and freeze-substituted, did not reveal
      the presence of a typical spindle. We propose that Giardia lamblia presents an
      uncommon mitotic behavior where the adhesive disc, a microtubular structure,
      seems to participate in the karyokinesis process.

PMID- 15145532
TI  - Glial progenitors in the CNS and possible lineage relationships among them.
AB  - Glial cells are derived from stem cells that mature through specific stages of
      development to generate fully differentiated astrocytes and oligodendrocytes.
      Several types of intermediate precursors have been described and in some cases
      lineage relationships identified although this remains a subject of controversy.
      We review recent findings and discuss some possibilities. Motoneuron
      oligodendrocyte precursors (MNOPs), white matter progenitor cells (WMPCs),
      polydendrocytes, glial restricted precursors (GRPs), astrocyte precursor cells
      (APCs), and oligodendroblasts are likely all derived from earlier appearing stem
      cells but segregate at different stages in development. Some of these precursors
      persist in the adult, and it is these glial progenitors rather than stem cells
      that respond after injury and participate in the repair process. Although which
      specific glial progenitor responds remains unclear, the availability of new
      markers will likely resolve this issue. We believe that the development of
      consensus sets of markers and an improvement in our ability to define stages of
      glial maturation will lead to a clearer appreciation of the importance of glia in
      the etiopathology of disease.

PMID- 15145534
TI  - Characterization of tissue specific expression of Notch-1 in human tissues.
AB  - Signaling through the Notch cell surface receptors is a highly conserved
      mechanism of cell fate specification. Notch signaling regulates proliferation,
      differentiation and cell death. In vertebrates, putative gene duplication has
      originated four Notch genes, Notch-1, -2, -3 and -4. They have been implicated in
      neurogenesis, hematopoiesis, T-cell development, vasculogenesis and brain
      cortical growth. We have investigated Notch-1 distribution in normal human
      tissues by immunohistochemistry and immunoblot. We detected widespread expression
      of Notch-1 cytoplasmatic staining, with different tissue distributions in the
      different organs examined. In particular, high expression of Notch-1 was detected
      in the intermediate suprabasal layers, but not in the dead cells at the extreme
      periphery of stratified epithelia. Moreover, a low/intermediate level of Notch-1
      was observed in lymphocytes in several peripheral lymphoid tissues; in particular
      the germinal centers of lymph nodes showed the most abundant number of positive
      cells, which appeared to be centroblasts/immunoblasts based on nuclear
      morphology. Notch-1 participates in keratinocytes differentiation. We showed by
      Western blot analysis that Notch-1 level was clearly increased in HaCaT cells
      after Ca(++) addition and remained substantially elevated until late
      differentiation stages. These results suggest that Notch-1 may function in
      numerous cell types in processes beyond cell fate determination, such as neuronal
      plasticity, muscle hypertrophy, liver regeneration, and germinal center
      lymphopoiesis during the immune response.

PMID- 15145535
TI  - Gel-to-gel phase transition may occur in mammalian cells: Mechanism of formation
      of "dark" (compacted) neurons.
AB  - In the course of many diseases, individual non-apoptotic cells that are randomly
      distributed among undamaged cells in various mammalian tissues become shrunken
      and hyperbasophilic ("dark"). The light microscopic shrinkage is caused by a
      potentially reversible, dramatic compaction of all ultrastructural elements
      inside the affected cells, and escape of the excess water through apparently
      intact plasma membrane. In the case of neurons, the ultrastructural compaction
      rapidly involves the soma-dendrite domains in an all-or-nothing manner, and also
      mm-long axon segments. The present paper demonstrates that such ultrastructural
      compaction in neurons, which affects the whole soma-dendrite domain or long axon
      segments, can take place both immediately after an in vivo head injury and in rat
      brains perfusion-fixed for 30 min., and then chilled to just above the freezing
      point before the same kind of head injury was inflicted. This argues strongly
      against any enzyme-mediated compaction mechanism. On the analogy of gel-to-gel
      phase transitions in polymer chemistry, we hypothesize a pure physico-chemical
      compaction mechanism. Specifically, after initiation at a single site in each
      affected cell, the ultrastructural compaction is propelled throughout the whole
      cell on the domino principle by the free energy stored in the form of non
      covalent interactions among the constituents of some cytoplasmic gel structure.

PMID- 15145536
TI  - Glial biology: functional interactions among glia and neurons.

PMID- 15145537
TI  - The problem of astrocyte identity.
AB  - Astrocytes were the original neuroglia of Ramon y Cajal but after 100 years there
      is no satisfactory definition of what should comprise this class of cells. This
      essay takes a historical and philosophical approach to the question of astrocytic
      identity. The classic approach of identification by morphology and location are
      too limited to determine new members of the astrocyte population. I also
      critically evaluate the use of protein markers measured by immunoreactivity, as
      well as the newer technique of marking living cells by using promoters for these
      same proteins to drive reporter genes. These two latter approaches have yielded
      an expanded population of astrocytes with diverse functions, but also mark cells
      that traditionally would not be defined as astrocytes. Thus we need a combination
      of measures to define an astrocyte but it is not clear what this combination
      should be. The molecular approach, especially promoter driven fluorescent
      reporter genes, does have the advantage of pre marking living astrocytes for
      electrophysiological or imaging recordings. However, lack of sufficient
      understanding of the behavior of the inserted constructs has led to unclear
      results. This approach will no doubt be perfected with time but at present an
      acceptable, practical definition of what constitutes the class of astrocytes
      remains elusive.

PMID- 15145538
TI  - Gene expression patterns in in vivo normal adult astrocytes compared with
      cultured neonatal and normal adult astrocytes.
AB  - This paper presents data on the basal gene expression patterns, determined by
      microarray analysis, for cultured neonatal and normal adult striatal astrocytes,
      and for comparison, for astrocytes isolated directly from adult rat striatum (in
      vivo adult astrocytes). Of the 1176 genes on the Clontech array, 1101 were
      expressed in one of the three types of astrocyte samples. Nineteen of the genes
      were expressed only in the astrocytes taken directly from adult rats (in vivo
      adult). The cultured neonatal astrocytes expressed many genes at a two-fold or
      greater level than their expression in cultured adult astrocytes, including genes
      in the adhesion, cytoskeleton, and extracellular matrix (ECM) family, signal
      transduction genes, and genes related to apoptosis, DNA-binding, and cell cycle
      regulation. Overall the results support the concept that cultured neonatal
      astrocytes are more "activated" than cultured adult cells, although the adult
      cells expressed higher levels of many metabolic enzyme and protease/protease
      inhibitor genes.

PMID- 15145539
TI  - Gene expression alterations in connexin null mice extend beyond the gap junction.
AB  - Connexin43 (Cx43) is the principal gap junction protein between astrocytes in the
      neonatal brain and also interconnects neural precursor cells during CNS
      development. In an attempt to understand global effects of expression of the Cx43
      gap junction gene on development and function of the nervous system, we have
      compared gene expression patterns in cultured astrocytes and brains from wildtype
      mice with those in which Cx43 is deleted as well as in spinal cords of
      experimental autoimmune encepahlomyelitis (EAE) mice. One surprising result
      obtained from high densitity mouse cDNA studies was the large number of genes
      that were statistically altered in mice with decreased expression of Cx43. These
      altered genes encode proteins with a wide range of functions within cells, and
      thus deletion of normal gap junction expression appears to result in globally
      altered glial functions in addition to disruption of intercellular communication.
      Here we discuss those results in the context of the strategies and data analysis
      paradigms that we are using in such studies.

PMID- 15145540
TI  - Contribution of astrocytes to synaptic transmission in the rat supraoptic
      nucleus.
AB  - Astrocytes, besides supporting metabolic and scaffolding functions, play a
      prominent role in the modulation of neuronal communication. In particular, they
      are responsible for clearing synaptically-released glutamate via highly specific
      transporters located on their plasma membrane. Since glutamate is the main
      excitatory neurotransmitter in the central nervous system (CNS), astrocytes are
      likely to play a central role in the regulation of synaptic processing and
      overall cellular excitability. We recently investigated the influence of
      astrocytes on glutamatergic and GABAergic transmission in the rat supraoptic
      nucleus (SON) of the hypothalamus. This nucleus is part of the hypothalamus
      neurohypophysial system (HNS), which constitutes a conspicuous example of
      activity-dependent neuroglial plasticity, in which certains physiological
      conditions, such as parturition, lactation, and dehydration are accompanied by a
      structural remodeling of the neurones, their synaptic inputs and their
      surrounding glia. The use of pharmacological inhibitors of glutamate transporters
      on this model, in which a physiological change in the astrocyte environment
      occurs, has brought new insights on the contribution of astrocytes to both
      excitatory and inhibitory neurotransmissions. The astrocytic environment of
      neurons appears to control glutamate uptake and diffusion in the extracellular
      space. This has direct repercussions on the tonic level of activation of
      presynaptic glutamate receptors and, as a consequence, on the release of
      neurotransmitter. This short review summarizes data obtained so far, which
      clearly support the view that astrocytes are indeed a third partner in synaptic
      transmission, and which show that the supraoptic nucleus represents a remarkable
      model to study dynamic physiological interactions between astrocytes and neurons.

PMID- 15145541
TI  - Mechanisms of glutamate release from astrocytes: gap junction "hemichannels",
      purinergic receptors and exocytotic release.
AB  - Neuronal exocytotic release of glutamate at synapses involves a highly
      specialized vesicular apparatus, consisting of a variety of proteins connected to
      the vesicles or required for vesicular fusion to the presynaptic membrane.
      Astrocytes also release glutamate, and recent evidence indicates that this
      release can modify neuronal function. Several mechanisms have been proposed for
      astrocytic release of glutamate under pathological conditions, such as reversal
      of glutamate transporters and opening of volume sensitive ion channels. In this
      review we limit our discussion to findings supporting the exocytotic release of
      glutamate, as well as two new pathways implicated in this release, the ionotropic
      (P2X) purinergic receptors and gap junction hemichannels.

PMID- 15145542
TI  - Neurons set the tone of gap junctional communication in astrocytic networks.
AB  - A number of studies have contributed to demonstrate that neurons and astrocytes
      tightly and actively interact. Indeed, the presence of astrocytes in neuronal
      cultures increases the number of synapses and their efficiency, and thanks to
      enzymatic and uptake processes, astrocytes play a role in neuroprotection. A
      typical feature of astrocytes is that they establish cell-cell communication in
      vitro, as well as in situ, through intercellular channels forming specialized
      membrane areas defined as gap junctions. These channels are composed of
      junctional proteins termed connexins (Cxs): in astrocytes connexin 43 (Cx43) and
      30 (Cx30) have been shown to prevail. Several recent works indicate that gap
      junctional communication (GJC) and/or connexin expression in astrocytes are
      controlled by neurons. Altogether, these observations lead to the concept that
      neuronal and astrocytic networks interact through mutual setting of their
      respective mode of communication and that astrocyte gap junctions represent a
      target in neuroglial interaction.

PMID- 15145543
TI  - Production of GABA by cultured hippocampal glial cells.
AB  - Medium conditioned by cultured hippocampal glial contains an inhibitory factor
      that can hyperpolarize and suppress neuronal activity. Using biochemistry,
      electrophysiology, pharmacology, and mass spectrometry, we have identified the
      inhibitory factor as GABA (gamma-aminobutyric acid). Like GABA, the inhibitory
      factor increases chloride and potassium currents in neurons, which can be blocked
      by bicuculline. Mass spectrometry analysis of conditioned medium reveals peaks
      that are identical to that for GABA. Up to 500 micromolar GABA is found in
      conditioned medium from glial cultures. No GABA is found in conditioned medium
      from neuronal cultures. Hippocampal glia make much more GABA than cortical glia
      or glia from other brain regions. It is not clear how hippocampal glia synthesize
      GABA. Although they express GAD mRNA and adding glutamate to the culture medium
      increases the amount of GABA produced, other data suggest that glia do not use
      GAD to make GABA. Identifying the mechanism(s) by which GABA is produced by
      hippocampal glia would help clarify its role in modulating neuronal activity in
      the brain.

PMID- 15145544
TI  - Intercellular metabolic compartmentation in the brain: past, present and future.
AB  - The first indication of 'metabolic compartmentation' in brain was the
      demonstration that glutamine after intracisternal [14C]glutamate administration
      is formed from a compartment of the glutamate pool that comprises at most one
      fifth of the total glutamate content in the brain. This pool, which was
      designated 'the small compartment,' is now known to be made up predominantly or
      exclusively of astrocytes, which accumulate glutamate avidly and express
      glutamine synthetase activity, whereas this enzyme is absent from neurons, which
      eventually were established to constitute 'the large compartment.' During the
      following decades, the metabolic compartment concept was refined, aided by
      emerging studies of energy metabolism and glutamate uptake in cellularly
      homogenous preparations and by the histochemical observations that the two key
      enzymes glutamine synthetase and pyruvate carboxylase are active in astrocytes
      but absent in neurons. It is, however, only during the last few years that
      nuclear magnetic resonance (NMR) spectroscopy, assisted by previously obtained
      knowledge of metabolic pathways, has allowed accurate determination in the human
      brain in situ of actual metabolic fluxes through the neuronal tricarboxylic acid
      (TCA) cycle, the glial, presumably mainly astrocytic, TCA cycle, pyruvate
      carboxylation, and the 'glutamate-glutamine cycle,' connecting neuronal and
      astrocytic metabolism. Astrocytes account for 20% of oxidative metabolism of
      glucose in the human brain cortex and accumulate the bulk of neuronally released
      transmitter glutamate, part of which is rapidly converted to glutamine and
      returned to neurons in the glutamate-glutamine cycle. However, one-third of
      released transmitter glutamate is replaced by de novo synthesis of glutamate from
      glucose in astrocytes, suggesting that at steady state a corresponding amount of
      glutamate is oxidatively degraded. Net degradation of glutamate may not always
      equal its net production from glucose and enhanced glutamatergic activity,
      occurring during different types of cerebral stimulation, including the
      establishment of memory, may be associated with increased de novo synthesis of
      glutamate. This process may contribute to a larger increase in glucose
      utilization rate than in rate of oxygen consumption during brain activation. The
      energy yield in astrocytes from glutamate formation is strongly dependent upon
      the fate of the generated glutamate.

PMID- 15145545
TI  - Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in
      vitro 13C NMR spectroscopy.
AB  - We review briefly 13C NMR studies of cerebral glucose metabolism with an emphasis
      on the roles of glial energetics and the glutamine cycle. Mathematical modeling
      analysis of in vivo 13C turnover experiments from the C4 carbons of glutamate and
      glutamine are consistent with: (i) the glutamine cycle being the major cerebral
      metabolic route supporting glutamatergic neurotransmission, (ii) glial glutamine
      synthesis being stoichiometrically coupled to glycolytic ATP production, (iii)
      glutamine serving as the main precursor of neurotransmitter glutamate and (iv)
      glutamatergic neurotransmission being supported by lactate oxidation in the
      neurons in a process accounting for 60-80% of the energy derived from glucose
      catabolism. However, more recent experimental approaches using inhibitors of the
      glial tricarboxylic acid (TCA) cycle (trifluoroacetic acid, TFA) or of glutamine
      synthase (methionine sulfoximine, MSO) reveal that a considerable portion of the
      energy required to support glutamine synthesis is derived from the oxidative
      metabolism of glucose in the astroglia and that a significant amount of the
      neurotransmitter glutamate is produced from neuronal glucose or lactate rather
      than from glial glutamine. Moreover, a redox switch has been proposed that allows
      the neurons to use either glucose or lactate as substrates for oxidation,
      depending on the relative availability of these fuels under resting or activation
      conditions, respectively. Together, these results suggest that the coupling
      mechanisms between neuronal and glial metabolism are more complex than initially
      envisioned.

PMID- 15145546
TI  - Intracellular metabolic compartmentation assessed by 13C magnetic resonance
      spectroscopy.
AB  - Our understanding of the brain has developed from the theory that it is one
      continuous cell to the knowledge that there are many brain cells originally
      termed neurons and, furthermore to the discovery of glial cells and their
      multiple functions. Thus, an increasing complexity was unraveled and we have not
      reached a complete understanding of the phenomenon which comprises the
      compartmentation of metabolic pathways and metabolites. This is an important
      principle needed to fully understand the metabolic processes of the brain. At the
      cellular level this concept is well established whereas intracellular
      compartmentation has yet to be explored. Using magnetic resonance spectroscopy
      (MRS) for analysis of isotopomer composition combined with quantification of
      amino acid contents it is possible to construct models that describe
      intracellular compartmentation. Results of studies of cultures of astrocytes and
      neurons incubated in media containing [U- 13C]glutamate in the presence or
      absence of thiopental may be used to propose an intracellular three compartment
      model of mitochondrial function. Due to the experimental paradigm only certain
      aspects of metabolism can be described. The present model consists of
      compartments assigned to CO(2) production, glutamate synthesis from ketoglutarate
      and finally synthesis of a four-carbon metabolite which is shuttled between
      compartments. It is likely that metabolism may be far more complex than this and
      we are only beginning to glimpse some aspects of compartmentation at the cellular
      level.

PMID- 15145547
TI  - Cultured retinal neuronal cells and Muller cells both show net production of
      lactate.
AB  - Glucose has long been considered the substrate for energy metabolism in the
      retina. Recently, an alternative hypothesis (metabolic coupling) suggested that
      mitochondria in retinal neurons utilize preferentially the lactate produced
      specifically by Muller cells, the principal glial cell in the retina. These two
      views of retinal metabolism were examined using confluent cultures of
      photoreceptor cells, Muller cells, ganglion cells, and retinal pigment epithelial
      cells incubated in modified Dulbecco's minimal essential medium containing
      glucose or glucose and lactate. The photoreceptor and ganglion cells represented
      neural elements, and the Muller and pigment epithelial cells represented non
      neural cells. The purpose of the present experiments was two-fold: (1) to
      determine whether lactate is a metabolic product or substrate in retinal cells,
      and (2) to examine the evidence that supports the two views of retinal energy
      metabolism. Measurements were made of lactic acid production, cellular ATP
      levels, and cellular morphology over 4 h. Results showed that all cell types
      incubated with 5 mM glucose produced lactate aerobically and anaerobically at
      linear rates, the anaerobic rate being 2-3-fold higher (Pasteur effect). Cells
      incubated with both 5 mM glucose and 10 mM lactate produced lactate aerobically
      and anaerobically at rates similar to those found when cells were incubated with
      glucose alone. Anaerobic ATP content in the cells was maintained at greater than
      50% of the control, aerobic value, and cellular morphology was well preserved
      under all conditions. The results show that the cultured retinal cells produce
      lactate, even in the presence of a high starting ambient concentration of
      lactate. Thus, the net direction of the lactic dehydrogenase reaction is toward
      lactate formation rather than lactate utilization. It is concluded that retinal
      cells use glucose, and not glial derived lactate, as their major substrate.

PMID- 15145548
TI  - Nutrition during brain activation: does cell-to-cell lactate shuttling contribute
      significantly to sweet and sour food for thought?
AB  - Functional activation of astrocytic metabolism is believed, according to one
      hypothesis, to be closely linked to excitatory neurotransmission and to provide
      lactate as fuel for oxidative metabolism in neighboring neurons. However, review
      of emerging evidence suggests that the energetic demands of activated astrocytes
      are higher and more complex than recognized and much of the lactate presumably
      produced by astrocytes is not locally oxidized during activation. In vivo
      activation studies in normal subjects reveal that the rise in consumption of
      blood-borne glucose usually exceeds that of oxygen, especially in retina compared
      to brain. When the contribution of glycogen, the brain's major energy reserve
      located in astrocytes, is taken into account the magnitude of the carbohydrate
      oxygen utilization mismatch increases further because the magnitude of
      glycogenolysis greatly exceeds the incremental increase in utilization of blood
      borne glucose. Failure of local oxygen consumption to equal that of glucose plus
      glycogen in vivo is strong evidence against stoichiometric transfer of lactate
      from astrocytes to neighboring neurons for oxidation. Thus, astrocytes, not
      nearby neurons, use the glycogen for energy during physiological activation in
      normal brain. These findings plus apparent compartmentation of metabolism of
      glycogen and blood-borne glucose during activation lead to our working hypothesis
      that activated astrocytes have high energy demands in their fine perisynaptic
      processes (filopodia) that might be met by glycogenolysis and glycolysis coupled
      to rapid lactate clearance. Tissue culture studies do not consistently support
      the lactate shuttle hypothesis because key elements of the model, glutamate
      induced increases in glucose utilization and lactate release, are not observed in
      many astrocyte preparations, suggesting differences in their oxidative capacities
      that have not been included in the model. In vivo nutritional interactions
      between working neurons and astrocytes are not as simple as implied by "sweet
      (glucose-glycogen) and sour (lactate) food for thought."

PMID- 15145550
TI  - Selective response of various brain cell types during neurodegeneration induced
      by mild impairment of oxidative metabolism.
AB  - Age-related neurodegenerative diseases are characterized by selective neuron
      loss, glial activation, inflammation and abnormalities in oxidative metabolism.
      Thiamine deficiency (TD) is a model of neurodegeneration induced by impairment of
      oxidative metabolism. TD produces a time-dependent, selective neuronal death in
      specific brain regions, while other cell types are either activated or
      unaffected. TD-induced neurodegeneration occurs first in a small, well-defined
      brain region, the submedial thalamic nucleus (SmTN). This discrete localization
      permits careful analysis of the relationship between neuronal loss and the
      response of other cell types. The temporal analysis of the changes in the region
      in combination with the use of transgenic mice permits testing of proposed
      mechanisms of how the interaction of neurons with other cell types produces
      neurodegeneration. Loss of neurons and elevation in markers of neurodegeneration
      are accompanied by changes in microglia including increased redox active iron,
      the induction of nitric oxide synthase (NOS) and hemeoxygenase-1, a marker of
      oxidative stress. Endothelial cells also show changes in early stages of TD
      including induction of intracellular adhesion molecule-1 (ICAM-1) and endothelial
      NOS. The number of degranulating mast cells also increases in early stages of TD.
      Alterations in astrocytes and neutrophils occur at later stages of TD. Studies
      with transgenic knockouts indicate that the endothelial cell changes are
      particularly important. We hypothesize that TD-induced abnormalities in oxidative
      metabolism promote release of neuronal inflammatory signals that activate
      microglia, astrocytes and endothelial cells. Although at early stages the
      responses of non-neuronal cells may be neuroprotective, at late phases they lead
      to entry of peripheral inflammatory cells into the brain and promote
      neurodegeneration.

PMID- 15145551
TI  - Changes in astrocyte mitochondrial function with stress: effects of Bcl-2 family
      proteins.
AB  - Mitochondria are central to both apoptotic and necrotic cell death, as well as to
      normal physiological function. Astrocytes are crucial for neuronal metabolic,
      antioxidant, and trophic support, as well as normal synaptic function. In the
      setting of stress, such as during cerebral ischemia, astrocyte dysfunction may
      compromise the ability of neurons to survive. Despite their central importance,
      the response of astrocyte mitochondria to stress has not been extensively
      studied. Limited data already suggest clear differences in the response of
      neuronal and astrocytic mitochondria to oxygen-glucose deprivation (GD).
      Prominent mitochondrial alterations during stress that can contribute to cell
      death include changes in production of reactive oxygen species (ROS) and release
      of death regulatory and signaling molecules from the intermembrane space. In
      response to stress mitochondrial respiratory function and membrane potential also
      change, and these changes appear to depend on cell type. Bcl-2 family proteins
      are the best studied regulators of cell death, especially apoptosis, and
      mitochondria are a major site of action for these proteins. Although much data
      supports the role of Bcl-2 family proteins in the regulation of some of these
      mitochondrial alterations, this remains an area of active investigation. This
      mini-review summarizes current knowledge regarding mitochondrial control of cell
      survival and death in astrocytes and the effects of anti-apoptotic Bcl-2 proteins
      on astrocyte mitochondrial function.

PMID- 15145549
TI  - Complement factors in adult peripheral nerve: a potential role in energy
      metabolism.
AB  - Complement cascade factors are known to play a critical role in myelin clearance
      after peripheral nerve injury. Here we show that components of both the classical
      (C1qa, C1qb, C1qc, C2 and C4) and alternative (C3, B and adipsin) pathways are
      expressed by uninjured peripheral nerve as well. mRNAs of components of the
      alternative pathway were predominantly found in the peri/epineurium, although
      factor C3 and factor B were also detected in the endoneurial compartment of adult
      nerve. Interestingly, adipsin mRNA was detected only in peri/epineurium, while
      adipsin protein was present in both peri/epineurium and endoneurium. This
      suggests that adipsin is transported to the endoneurium via the circulation from
      the peri/epineurium or outside of the nerve. Factor 5 and factor 9, necessary for
      the formation of the membrane-attack complex, were not detected in any part of
      the healthy peripheral nerve, which together with the observed presence of
      negative regulators of complement activation, is likely to prevent damage to the
      healthy nerve caused by complement activation. By analogy with the known role of
      complement factors in fat, we propose that local expression of these factors
      plays a role in the regulation of fatty acid homeostasis in the nerve and,
      thereby, in energy metabolism cross-talk between different compartments of the
      peripheral nerve.

PMID- 15145552
TI  - Attenuation of a delayed increase in the extracellular glutamate level in the
      peri-infarct area following focal cerebral ischemia by a novel agent ONO-2506.
AB  - A novel agent, ONO-2506 [(R)-(-)-2-propyloctanoic acid, ONO Pharmaceutical Co.
      Ltd.] was previously shown to mitigate delayed infarct expansion through
      inhibition of the enhanced production of S-100beta, while inducing a prompt
      symptomatic improvement that attained a significant level as early as 24h after
      drug administration. To elucidate the mechanism underlying the prompt symptomatic
      improvement, the present study aimed to examine whether ONO-2506 modulates the
      level of extracellular glutamate ([Glu]e) in the rat subjected to transient
      middle cerebral artery occlusion (tMCAO). In this model, it had been shown that
      ONO-2506 reduces the infarct volume, improves the neurological deficits, and
      enhances the mRNA expression of glial glutamate transporters (GLT-1 and GLAST).
      The [Glu]e levels in the ischemic cortices were continuously measured using
      intracerebral microdialysis. The alterations in the [Glu]e levels in the sham
      operated and tMCAO-operated groups with or without drug administration were
      compared. In the tMCAO groups, the [Glu]e level increased during tMCAO to a
      similar extent, returned to normal on reperfusion, and increased again around 5h.
      In the saline-treated group, however, the [Glu]e level further increased from 15
      h on to reach about 280% of the normal level at 24h. This secondary increase in
      the [Glu]e level in the late phase of reperfusion was prevented by ONO-2506. The
      intracerebral infusion of glutamate transporter inhibitor, l-trans-pyrrolidine
      2,4-dicarboxylic acid, at 24h after tMCAO induced an increase in the [Glu]e
      level, which was marked in both the sham-operated and ONO-2506-treated groups,
      but much less pronounced in the saline-treated group. The above results suggest
      that functional modulation of activated astrocytes by pharmacological agents like
      ONO-2506 may inhibit the secondary rise of [Glu]e level in the late phase of
      reperfusion, leading to amelioration of delayed infarct expansion and
      neurological deficits.

PMID- 15145553
TI  - Glial activation and pathological pain.
AB  - Pain is a sensation we have all experienced. For most of us, the pain has been
      temporary. However, for patients with pathological pain, the pain experience is
      unending, with little hope for therapeutic relief. Pathological pain is
      characterized by an amplified response to normally innocuous stimuli, and an
      amplified response to acute pain. Pathological pain has long been described as
      the result of dysfunctional neuronal activity. While neuronal functioning is
      indeed altered, there is significant evidence showing that exaggerated pain is
      regulated by the activation of astrocytes and microglia. In exaggerated pain,
      astrocytes, and microglia are activated by neuronal signals including substance
      P, glutamate, and fractalkine. Activation of glia by these substances leads to
      the release of mediators that then act on other glia and neurons. These include a
      family of proteins called "proinflammatory cytokines" released from microglia and
      astrocytes. These cytokines have been shown to be critical mediators of
      exaggerated pain. Some patients with pathological pain also report "extra
      territorial" and/or "mirror" image pain. That is, exaggerated pain is experienced
      not only in the area of trauma. In extra-territorial pain, pain is also perceived
      as arising from neighboring healthy tissues outside of the site of trauma. In the
      rare cases of mirror-image pain, such pain is perceived as arising from the
      healthy, corresponding body part on the opposite side of the body. New data
      suggest that activation of astrocyte communication via gap junctions may mediate
      such spread of pain. While traditional therapies for pathological pain have
      focused on neuronal targets, the following review describes glia as newly
      recognized mediators of exaggerated pain, and as new therapeutic targets.
      Moreover, the glial-neuronal interactions discussed here are likely not exclusive
      to pain, but rather are likely to play significant roles in other behavioral
      phenomena.

PMID- 15145554
TI  - Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic
      activation markers in a rat model of neuropathic pain.
AB  - Activated spinal glial cells have been strongly implicated in the development and
      maintenance of persistent pain states following a variety of stimuli including
      traumatic nerve injury. The present study was conducted to characterize the time
      course of surface markers indicative of microglial and astrocytic activation at
      the transcriptional level following an L5 nerve transection that results in
      behavioral hypersensitivity. Male Sprague-Dawley rats were divided into a normal
      group, a sham surgery group with an L5 spinal nerve exposure and an L5 spinal
      nerve transected group. Mechanical allodynia (heightened response to a non
      noxious stimulus) of the ipsilateral hind paw was assessed throughout the study.
      Spinal lumbar mRNA levels of glial fibrillary acidic protein (GFAP), integrin
      alpha M (ITGAM), toll-like receptor 4 (TLR4) and cluster determinant 14 (CD14)
      were assayed using real-time reverse transcription polymerase chain reaction (RT
      PCR) at 4 h, 1, 4, 7, 14 and 28 days post surgery. The spinal lumbar mRNA
      expression of ITGAM, TLR4, and CD14 was upregulated at 4 h post surgery, CD14
      peaked 4 days after spinal nerve transection while ITGAM and TLR4 continued to
      increase until day 14 and returned to almost normal levels by postoperative day
      28. In contrast, spinal GFAP mRNA did not significantly increase until
      postoperative day 4 and then continued to increase over the duration of the
      study. Our optimized real-time RT-PCR method was highly sensitive, specific and
      reproducible at a wide dynamic range. This study demonstrates that peripheral
      nerve injury induces an early spinal microglial activation that precedes
      astrocytic activation using mRNA for surface marker expression; the delayed but
      sustained expression of mRNA coding for GFAP implicates astrocytes in the
      maintenance phase of persistent pain states. In summary, these data demonstrate a
      distinct spinal glial response following nerve injury using real-time RT-PCR.

PMID- 15145555
TI  - Early glial responses in murine models of multiple sclerosis.
AB  - Investigations of functional interactions among axons and glia over the last
      decade have revealed the extent and complexity of glial-neuronal and glial-glial
      communication during development, adult function and recovery from injury. These
      data have profound implications for the understanding of central nervous system
      (CNS) disorders, which until recently, have been classified as either neuronal or
      glial diseases. Re-evaluation of the pathological processes in a number of
      conditions has clearly shown involvement of both neurons and glia in early
      pathology. In multiple sclerosis (MS), the myelin sheath has traditionally been
      regarded as the primary target. However, recent evidence has clearly demonstrated
      axonal damage in new lesions. We have addressed the question of the role of
      axonal pathology in early MS by using well-characterized murine models for the
      relapsing-remitting (RR) or the primary progressive (PP) forms of the disease. We
      performed a histopathological survey of the CNS, following induction of the
      disease, to determine the timing of appearance, as well as the development of
      lesions. Then we analysed the relationship between inflammation, demyelination
      and axonal damage together with responses from astrocytes and microglia in each
      model from the earliest evidence of inflammation. We found that axonal damage
      begins well ahead of the appearance of motor symptoms. Pathology appears to be
      more closely related to the degree of inflammation than to demyelination. We also
      show that early astrocyte responses and the degree of axonal loss are markedly
      different in the two models and relate to the severity of pathology. These data
      support the now widely accepted hypothesis that axonal damage begins early in the
      disease process, but also suggest modulation of axonal loss and disease
      progression by the astrocytic response.

PMID- 15145556
TI  - Expression of connexins during development and following manipulation of afferent
      input in the rat locus coeruleus.
AB  - Synchronous activity of locus coeruleus (LC) neurons during early postnatal
      development is regulated, in part, by electrotonic coupling. Connexin (Cx)
      proteins that make up gap junction channels are localized to both neurons and
      glia in the LC during this period. In adult rats, however, synchrony exists only
      under certain experimental conditions. The expression of Cx proteins was examined
      using western blot analysis at several developmental time points. Immunoblot
      analysis revealed little to no expression of Cx26 while Cx32, Cx43 and Cx36 were
      present at all time points examined. A progressive increase in Cx43 was
      identified from the first postnatal week through adulthood. Immunocytochemical
      detection of Cx36 and Cx43 in adult LC showed that Cx36 was associated with
      neuronal processes while Cx43 was localized to glia. In adult LC, in vitro
      intracellular recordings combined with neurobiotin injections confirmed the
      presence of gap junctional communication albeit to a lesser extent than in early
      postnatal periods. The degree to which synaptic inputs to LC neurons impact on Cx
      protein expression was also evaluated. Samples of the LC from rats that received
      an electrolytic lesion of the amygdala were processed for western blot analysis
      of Cx36 and Cx43. The predominantly neuronal Cx36 exhibited an increase in
      expression while the glial Cx43 was unchanged. The present results indicate that,
      despite subtype-specific changes during development, several Cx proteins are
      expressed in the adult LC. In addition, manipulating afferent input to the LC, in
      adult rats, results in increases in neuronal Cx protein levels but not in glial
      Cx levels suggesting that altering synaptic inputs to the LC may alter
      synchronous activity in noradrenergic neurons.

PMID- 15145557
TI  - Effects of neuroinflammation on glia-glia gap junctional intercellular
      communication: a perspective.
AB  - Gap junctions serve as intercellular conduits that allow for the direct transfer
      of small molecular weight molecules (up to 1 kDa) including ions involved in
      cellular excitability, metabolic precursors, and second messengers. The
      observation of extensive intercellular coupling and large numbers of gap
      junctions in the central nervous system (CNS) suggests a syncytium-like
      organization of glial compartments. Inflammation is a hallmark of various CNS
      diseases such as bacterial and viral infections, multiple sclerosis, Alzheimer's
      disease, and cerebral ischemia. A general consequence of brain inflammation is
      reactive gliosis typified by astrocyte hypertrophy and proliferation of
      astrocytes and microglia. Changes in gap junction intercellular communication as
      reflected by alterations in dye coupling and connexin expression have been
      associated with numerous CNS inflammatory diseases, which may have dramatic
      implications on the survival of neuronal and glial populations in the context of
      neuroinflammation. A review of the effects of inflammatory products on glia-glia
      gap junctional communication and glial glutamate release is presented. In
      addition, the hypothesis of a "syncytial switch" based upon differential
      regulation of gap junction expression in astrocytes and microglia during normal
      CNS homeostasis and neuroinflammation is proposed.

PMID- 15145558
TI  - Kinin receptors in cultured rat microglia.
AB  - Kinins are produced and act at the site of injury and inflammation in various
      tissues. They are likely to initiate a particular cascade of inflammatory events,
      which evokes physiological and pathophysiological responses including an increase
      in blood flow and plasma leakage. In the central nervous system (CNS), kinins are
      potent stimulators of the production and release of pro-inflammatory mediators
      represented by prostanoids and cytotoxins. They are known to induce neural tissue
      damage. Many of the cytotoxins such as cytokines and free radicals and
      prostanoids are released from glial cells. Among glial cells, astrocytes and
      oligodendrocytes are known to possess bradykinin (BK) B(2) receptors that
      phosphoinositide (PI) turnover and raise intracellular Ca(2+) concentration. The
      presence of bradykinin receptors in microglia has been of great significance. We
      recently showed that rat primary microglia express kinin receptors. In resting
      microglia, B(2) receptors but not B(1) receptors are expressed. When the
      microglia are activated by bradykinin, B(1) receptors are up-regulated, while
      B(2) receptors are down-regulated. As observed in other glial cells,
      electrophysiological measurements suggest that B(2) receptors in phosphoinositide
      turnover and intracellular Ca(2+) concentration in microglia. Release of
      cytotoxins is likely consequent upon the activation of BK receptors. Our study
      provides the first evidence that microglia express functional kinin receptors and
      suggests that microglia play an important role in CNS inflammatory responses.

PMID- 15145559
TI  - The effective source area of 90Sr for a stream near Chernobyl, Ukraine.
AB  - Remediation of streams impacted by non-point source contaminants requires an
      understanding of both the areas within a watershed that are contributing
      contamination to streams and the pathways of contaminant migration to streams.
      From 1998 to 2002, we studied the migration of 90Sr in the Borschi watershed, a
      small (8.5 km2) catchment three km south of the Chernobyl Nuclear Power Plant,
      Ukraine. Fuel particles, distributed in a heterogeneous pattern across the
      watershed, are weathering and releasing 90Sr from the fuel matrix. Depletion of
      (90)Sr, evaluated in comparison to the immobile fission product europium-154, is
      occurring in the channel and wetland sediment. Channel sediments are uniformly
      depleted in 90Sr with depth. In wetland sediments, there is a zone of depletion
      in the top 10 cm and a zone of accumulation at depths from 10 to 25 cm. Estimates
      of 90Sr depletion are used to map the effective source area that has contributed
      (90)Sr loading to the main channel. The effective source area includes channel
      bottom sediments, a wetland in the central region of the watershed, and
      periodically flooded soils surrounding the wetland. The total depletion from the
      effective source area is estimated to be 36 +/- 7 x 10(10) Bq. Based on
      observations of stream flow rate and water quality in 1999-2001, the annual 90Sr
      removal rate from the watershed is estimated to be 1.4 +/-0.2 x 10(10) or 1.5% of
      the inventory per year. When extrapolated over a 15-year period following the
      Chernobyl accident, the last value is in reasonable agreement with the estimated
      depletion of the source area based on 90Sr/154Eu ratios. The 90Sr yearly leaching
      rate considering the whole watershed is 0.2% while the 90Sr leaching rate
      considering the effective source area is an order of magnitude higher. Most of
      the 90Sr release in the watershed has originated from an effective source area of
      0.62 km2, or 7% of the watershed area.

PMID- 15145560
TI  - Improving the extraction of tetrachloroethylene from soil columns using
      surfactant gradient systems.
AB  - In this work, we extend the recently developed gradient approach for surfactant
      enhanced remediation of dense non-aqueous phase liquid (DNAPL)-impacted sites.
      The goal of the gradient approach is to maximize the DNAPL solubilization
      capacity in swollen micelles (Type I aqueous microemulsions) while at the same
      time minimizing the potential for DNAPL mobilization. In this work, we introduce
      a modified version of the capillary/trapping curve that we refer to as the
      gradient curve to help interpret and/or design the gradient approach. The
      gradient curve presents the residual DNAPL saturation as a function of
      interfacial tension and microemulsion viscosity. This approach demonstrates that
      keeping a low viscosity of the microemulsion phase is not only important for
      keeping a low head loss during surfactant flooding but also to prevent oil
      mobilization. Eight microemulsion systems were evaluated in this research; these
      systems were evaluated based on their tetrachloroethylene (PCE) solubilization
      capacity, interfacial tension (IFT), viscosity, density, and coalescence
      kinetics. Two of these systems were chosen for evaluation in site-specific column
      tests using an increasing electrolyte gradient to produce a decreasing
      IFT/increasing solubilization gradient system. The column studies were conducted
      with media from Dover Air Force Base in Dover, DE. Both solubilized and mobilized
      DNAPL were quantified. During the column studies, we observed that substantial
      PCE was mobilized when the residual level of PCE in the column was significantly
      higher than the steady-state residual saturation level being approach (as
      predicted from the gradient curve). Four column studies were performed, three of
      which were used to asses the validity of the gradient curve in predicting the
      residual saturation after each gradient step. From these tests we observed that
      starting IFTs of less than 1 mN/m all produced the same mobilization potential.
      In the last column, we used an additional gradient step with an initial IFT above
      1 mN/m to dramatically reduce the amount of PCE mobilize. Based on the good
      agreement between column results and projections based on the gradient curve, we
      propose this as a preferred method for designing gradient surfactant flushing
      systems.

PMID- 15145561
TI  - Infiltration and redistribution of LNAPL into unsaturated layered porous media.
AB  - Enhanced understanding of light non-aqueous phase liquid (LNAPL) infiltration
      into heterogeneous porous media is important for the effective design of
      remediation strategies. We used a 2-D experimental facility that allows for
      visual observation of LNAPL contours in order to study LNAPL redistribution in a
      layered porous medium. The layers are situated in the unsaturated zone near the
      watertable and they are inclined to be able to observe the effect of
      discontinuities in capillary forces and relative permeabilities. Two experiments
      were performed. The first experiment consisted of LNAPL infiltration into a fine
      sand matrix with a coarse sand layer, and the second experiment consisted of a
      coarse sand matrix and a fine sand layer. The numerical multi-phase flow model
      STOMP was validated with regard to the experimental results. This model is able
      to adequately reproduce the experimental LNAPL contours. Numerical sensitivity
      analysis was also performed. The capillarity contrast between sands was found to
      be the main controlling factor determining the final LNAPL distribution.

PMID- 15145562
TI  - The application of ground penetrating radar attenuation tomography in a vadose
      zone infiltration experiment.
AB  - Cross-borehole ground penetrating radar (XBGPR) is used in monitoring a long-term
      vadose zone infiltration experiment at a test site in Socorro, NM in order to
      examine contaminant transport in the vadose zone. XBGPR attenuation tomography is
      conducted in order to test the ability of using images of electromagnetic
      attenuation for hydrogeologic investigations. The results of four pre
      infiltration attenuation inversions shows standard deviations below 0.1 Np/m, and
      demonstrate the consistency of the XBGPR tomography technique for making time
      lapse observations. Correlation to the core records indicates that XBGPR
      attenuation tomograms provide high-resolution images of clay distribution in the
      vadose zone. Water infiltration at the ground surface was initiated in February
      1999 at a constant rate of 2.7 cm/day, and continued at this rate throughout the
      data collection experiment. Time-lapse attenuation tomograms show that
      attenuation increases by approximately 0.3 Np/m during the water infiltration,
      and indicate a snowplow effect may be occurring where salts are dissolved by the
      water and concentrated at the front of the plume. Seasonal temperature changes
      may also cause changes in electromagnetic attenuation images, and masking the
      evidence of water infiltration. Thus caution must be taken when using time-lapse
      attenuation images to interpret the movement of a water plume during a long-term
      experiment as temperature changes.

PMID- 15145563
TI  - Multiphase flow and transport through fractured heterogeneous porous media.
AB  - The migration of Dense, Non-Aqueous Phase Liquid (DNAPL) and dissolved phase
      contamination through a fractured heterogeneous porous medium has been
      investigated through the use of a multiphase compositional model. The sensitivity
      of the timescales of migration and the distribution of contaminant in the
      subsurface to the mean permeability, the variance of the permeability, and the
      degree of fracturing of the domain were examined. It was found that increasing
      the mean permeability of the domain allowed the DNAPL to penetrate deeper into
      the subsurface, while decreasing the mean permeability caused the DNAPL to pool
      at shallower depths. The presence of fractures within the system was found to
      control the infiltration only in the most fractured domain. Moment analysis of
      the nonwetting phase showed that large-scale movement had ceased after
      approximately 9 years (maximum duration of the source-on condition was
      approximately 4.5 years). This tended to be due to a redistribution of the DNAPL
      towards a residual configuration, as was evidenced by the gradual trending of
      average nonwetting phase saturations within the domain to a static value. The
      dissolved phase plume was found to migrate at essentially the same rate as the
      nonwetting phase, due to the reduced relative permeability of lenses containing
      DNAPL, and due to diffusive losses of mass to the matrix of fractured clay and
      silty-clay lenses. Some exceptions to this were found when the DNAPL could not
      overcome the displacement pressure of a lens, and could not by-pass the lens due
      to the lack of available driving force after the source had been shut off.

PMID- 15145564
TI  - Cesium migration in saturated silica sand and Hanford sediments as impacted by
      ionic strength.
AB  - Large amounts of 137Cs have been accidentally released to the subsurface from the
      Hanford nuclear site in the state of Washington, USA. The cesium-containing
      liquids varied in ionic strengths, and often had high electrolyte contents,
      mainly in the form of NaNO3 and NaOH, reaching concentrations up to several moles
      per liter. In this study, we investigated the effect of ionic strengths on Cs
      migration through two types of porous media: silica sand and Hanford sediments.
      Cesium sorption and transport was studied in 1, 10, 100, and 1000 mM NaCl
      electrolyte solutions at pH 10. Sorption isotherms were constructed from batch
      equilibrium experiments and the batch-derived sorption parameters were compared
      with column breakthrough curves. Column transport experiments were analyzed with
      a two-site equilibrium-nonequilibrium model. Cesium sorption to the silica sand
      in batch experiments showed a linear sorption isotherm for all ionic strengths,
      which matched well with the results from the column experiments at 100 and 1000
      mM ionic strength; however, the column experiments at 1 and 10 mM ionic strength
      indicated a nonlinear sorption behavior of Cs to the silica sand. Transport
      through silica sand occurred under one-site sorption and equilibrium conditions.
      Cesium sorption to Hanford sediments in both batch and column experiments was
      best described with a nonlinear Freundlich isotherm. The column experiments
      indicated that Cs transport in Hanford sediments occurred under two-site
      equilibrium and nonequilibrium sorption. The effect of ionic strength on Cs
      transport was much more pronounced in Hanford sediments than in silica sands.
      Effective retardation factors of Cs during transport through Hanford sediments
      were reduced by a factor of 10 when the ionic strength increased from 100 to 1000
      mM; for silica sand, the effective retardation was reduced by a factor of 10 when
      ionic strength increased from 1 to 1000 mM. A two order of magnitude change in
      ionic strength was needed in the silica sand to observe the same change in Cs
      retardation as in Hanford sediments.

PMID- 15145565
TI  - Assessing microbial degradation of o-xylene at field-scale from the reduction in
      mass flow rate combined with compound-specific isotope analyses.
AB  - In recent years, natural attenuation (NA) has evolved into a possible remediation
      alternative, especially in the case of BTEX spills. In order to be approved by
      the regulators, biodegradation needs to be demonstrated which requires efficient
      site investigation and monitoring tools. Three methods--the Integral Groundwater
      Investigation method, the compound-specific isotope analysis (CSIA) and a newly
      developed combination of both--were used in this work to quantify at field scale
      the biodegradation of o-xylene at a former gasworks site which is heavily
      contaminated with BTEX and PAHs. First, the Integral Groundwater Investigation
      method [Schwarz, R., Ptak, T., Holder, T., Teutsch, G., 1998. Groundwater risk
      assessment at contaminated sites: a new investigation approach. In: Herbert, M.
      and Kovar, K. (Editors), GQ'98 Groundwater Quality: Remediation and Protection.
      IAHS Publication 250, pp. 68-71; COH 4 (2000) 170] was applied, which allows the
      determination of mass flow rates of o-xylene by integral pumping tests.
      Concentration time series obtained during pumping at two wells were used to
      calculate inversely contaminant mass flow rates at the two control planes that
      are defined by the diameter of the maximum isochrone. A reactive transport model
      was used within a Monte Carlo approach to identify biodegradation as the dominant
      process for reduction in the contaminant mass flow rate between the two
      consecutive control planes. Secondly, compound-specific carbon isotope analyses
      of o-xylene were performed on the basis of point-scale samples from the same two
      wells. The Rayleigh equation was used to quantify the degree of biodegradation
      that occurred between the wells. Thirdly, a combination of the Integral
      Groundwater Investigation method and the compound-specific isotope analysis was
      developed and applied. It comprises isotope measurements during the integral
      pumping tests and the evaluation of delta13C time series by an inversion
      algorithm to obtain spatially integrated mean isotope values at the control
      planes. It was shown that the Rayleigh equation is applicable to spatially
      integrated mean isotope values in order to obtain the mean biodegradation between
      the consecutive control planes. All three approaches yielded consistently a 98
      99% degradation of o-xylene.

PMID- 15145566
TI  - TCE recovery mechanisms using micellar and alcohol solutions: phase diagrams and
      sand column experiments.
AB  - Forty-one phase diagrams and fifteen sand column experiments were conducted to
      evaluate the efficiency of three types of washing solutions to recover
      trichloroethylene (TCE) at residual saturation and to identify the recovery
      mechanisms involved. This study demonstrates that: (1) an alcohol and a
      surfactant combination is more efficient than an alcohol used alone in water; (2)
      the prediction of the dominant recovery mechanism from the tie line slopes in
      phase diagram is accurate and can be reproduced in sand column experiments; and
      (3) TCE recovery efficiency in sand column experiments is generally well
      represented by the position of the miscibility curve in phase diagrams in the low
      concentration range. However, the miscibility curve alone is not sufficient to
      exactly predict the TCE recovery mechanisms involved. Tie line slopes and the
      critical tie line have to be taken into consideration to select the active matter
      as well as its concentration and to predict the dominant recovery mechanism in
      sand column experiments. The sand column experiments quantified the recovery
      efficiency of each solution and identified the proportion of the recovery
      mechanisms (mobilisation vs. solubilisation). Washing solutions with an active
      matter concentration above the critical tie line caused dominating mobilisation.
      Mobilisation was also dominant when the active matter of the washing solution
      partitioned into the organic phase and the active matter concentration was below
      the critical tie line. Solubilisation and emulsification were dominant for
      washing solutions containing active matter, which principally partitioned into
      the aqueous phase and an active matter concentration below the critical tie line.

PMID- 15145567
TI  - Contributions of advective and diffusive oxygen transport through multilayer
      composite caps over mine waste.
AB  - The relative contributions of four mechanisms of oxygen transport in multilayer
      composite (MLC) caps placed over oxygen-consuming mine waste were evaluated using
      numerical and analytical methods. MLC caps are defined here as caps consisting of
      earthen and geosynthetic (polymeric) components where a composite barrier layer
      consisting of a geomembrane (1-2 mm thick polymeric sheet) overlying a clay layer
      is the primary barrier to transport. The transport mechanisms that were
      considered are gas-phase advective transport, gas-phase diffusive transport,
      liquid-phase advective transport via infiltrating precipitation and liquid-phase
      diffusive transport. A numerical model was developed to simulate gas-phase
      advective-diffusive transport of oxygen through a multilayer cap containing seven
      layers. This model was also used to simulate oxygen diffusion in the liquid
      phase. An approximate analytical method was used to compute the advective flux of
      oxygen in the liquid phase. The numerical model was verified for limiting cases
      using an analytical solution. Comparisons were also made between model
      predictions and field data for earthen caps reported by others. Results of the
      analysis show that the dominant mechanism for oxygen transport through MLC caps
      is gas-phase diffusion. For the cases that were considered, the gas-phase
      diffusive flux typically comprises at least 99% of the total oxygen flux. Thus,
      designers of MLC caps should focus on design elements and features that will
      limit diffusion of gas-phase oxygen.

PMID- 15145568
TI  - Impact of edible oil injection on the permeability of aquifer sands.
AB  - Recent laboratory and field studies have shown that food-grade edible oils can be
      injected into the subsurface for installation of in-situ permeable reactive
      barriers. However to be effective, the oil must be distributed out away from the
      oil injection points without excessive permeability loss. In this work, we
      examine the distribution of soybean oil in representative aquifer sediments as
      non-aqueous phase liquid oil (NAPL oil) or as an oil-in-water emulsion.
      Laboratory columns packed with sands or clayey sands were flushed with either
      NAPL oil or a soybean emulsion followed by plain water, while monitoring
      permeability loss and the final oil residual saturation. NAPL oil can be injected
      into coarse-grained sands. However NAPL injection into finer grained sediments
      requires high injection pressures which may not be feasible at some sites. In
      addition, NAPL injection results in high oil residual saturations and moderate
      permeability losses. In contrast, properly prepared emulsions can be distributed
      through sands with varying clay content without excessive pressure buildup, low
      oil retention and very low to moderate permeability loss. For effective
      transport, the emulsion must be stable, the oil droplets must be significantly
      smaller than the mean pore size of the sediment and the oil droplets should have
      a low to moderate tendency to stick to each other and the aquifer sediments. In
      our work, oil retention and associated permeability loss increased with sediment
      clay content and with the ratio of droplet size to pore size. For sandy
      sediments, the permeability loss is modest (0-40% loss) and is proportional to
      the oil residual saturation.

PMID- 15145569
TI  - Equilibrium nonaqueous phase liquid pool geometry in coarse soils with discrete
      textural interfaces.
AB  - This paper presents a model for the geometry of nonaqueous phase liquid (NAPL)
      pools and mounds in homogeneous soils and soils with discrete textural
      interfaces. It is shown that the concepts of capillary pressure-saturation curve
      hysteresis and entry pressures are integral to the complete conceptualization of
      pool and mound geometry. Unless hysteresis is included in the analysis, light
      NAPL (LNAPL) in homogeneous soils cannot exist in pools at all, and dense NAPL
      (DNAPL) will not mound on horizontal textural interfaces unless lateral confining
      boundaries are present. The proposed model also implies that remobilization of
      DNAPL pools will occur at lower hydraulic gradients than those predicted with
      previous models. Comparing predicted and experimental DNAPL and LNAPL pool
      thicknesses and the location of an LNAPL lens with respect to the top of the
      capillary fringe validate the model.

PMID- 15145570
TI  - A constitutive model for air-NAPL-water flow in the vadose zone accounting for
      immobile, non-occluded (residual) NAPL in strongly water-wet porous media.
AB  - A hysteretic constitutive model describing relations among relative
      permeabilities, saturations, and pressures in fluid systems consisting of air,
      nonaqueous-phase liquid (NAPL), and water is modified to account for NAPL that is
      postulated to be immobile in small pores and pore wedges and as films or lenses
      on water surfaces. A direct outcome of the model is prediction of the NAPL
      saturation that remains in the vadose zone after long drainage periods (residual
      NAPL). Using the modified model, water and NAPL (free, entrapped by water, and
      residual) saturations can be predicted from the capillary pressures and the water
      and total-liquid saturation-path histories. Relations between relative
      permeabilities and saturations are modified to account for the residual NAPL by
      adjusting the limits of integration in the integral expression used for
      predicting the NAPL relative permeability. When all of the NAPL is either
      residual or entrapped (i.e., no free NAPL), then the NAPL relative permeability
      will be zero. We model residual NAPL using concepts similar to those used to
      model residual water. As an initial test of the constitutive model, we compare
      predictions to published measurements of residual NAPL. Furthermore, we present
      results using the modified constitutive theory for a scenario involving NAPL
      imbibition and drainage.

PMID- 15145571
TI  - Effect of scale and dimensionality on the surfactant-enhanced solubilization of a
      residual DNAPL contamination.
AB  - The mass transfer rate from residual dense non-aqueous phase liquids (DNAPLs) to
      the mobile aqueous phase is an important parameter for the efficiency of
      surfactant-enhanced remediation through solubilization of this type of
      contamination. The mass transfer kinetics are highly dependent on the
      dimensionality of the system. In this study, irregularly shaped residual TCE
      saturations in two-dimensional saturated flow fields were flushed with a 2%
      polyoxyethylene sorbitan (20) monooleate (POESMO) solution until complete removal
      had been achieved. A numerical model was developed and used for the simulation of
      the various surfactant-flushing experiments with different initial saturation
      patterns and flow rates. Through optimization against in situ concentration and
      saturation data, a phenomenological power-law model for the relationship between
      the mass transfer rate from the DNAPL to the mobile aqueous phase on the one hand
      and the residual DNAPL saturation and the flow velocity on the other hand was
      derived. The obtained mass transfer rate parameters provide a reasonable fit to
      the experimental data, predicting the cleanup time and the general saturation and
      concentration pattern quite well but failing to predict the concentration curves
      at every individual sampling port. The obtained mass transfer rate model gives
      smaller values for the predicted mass transfer rate but shows a comparable
      dependence on water flow and saturation as in earlier published one-dimensional
      column experiments with identical characteristics for porous medium, DNAPL and
      surfactant. Mass transfer rate predictions were about one order of magnitude
      lower in the 2-D flow cell experiment than in 1-D column experiments. These
      results give an indication for the importance of dimensionality during surfactant
      remediation.

PMID- 15145572
TI  - Transcripts of aging.
AB  - Recently, it has been demonstrated that similar alterations in gene expression
      profiles occur in cells from patients with Werner syndrome and from normally aged
      individuals. Changes involving the genes that are involved in RNA and DNA
      metabolism were particularly frequent - highlighting the importance of the smooth
      progression of replication and transcription for maintaining youthful vigor. In
      this article, we discuss the implications of this work for our understanding of
      the molecular basis of aging and the increasingly important role of microarrays
      for unraveling the functional pathways underlying the aging phenotype.

PMID- 15145573
TI  - Activation induced deaminase: the importance of being specific.
AB  - Activation-induced deaminase (AID) is required for class switch recombination and
      somatic hypermutation in immunoglobulin genes. Although the preponderance of
      evidence suggests that AID functions by deaminating deoxycytidine in DNA, the
      question remains whether it can also deaminate cytidine in mRNA, as originally
      proposed based on its homology to RNA-editing enzymes. Recently, the biological
      relevance of assaying mammalian enzymes for DNA deaminase activity using
      Escherichia coli DNA as a reporter has been questioned, representing another
      round in the ongoing debate.

PMID- 15145574
TI  - Genomic analysis of essentiality within protein networks.
AB  - In this article, we introduce the notion of 'marginal essentiality' through
      combining quantitatively the results from large-scale phenotypic experiments
      (e.g. growth rate inhibition from knockouts). We find that this quantity relates
      to many of the topological characteristics of protein-protein interaction
      networks. In particular, proteins with a greater degree of marginal essentiality
      tend to be network hubs (i.e. with many interactions) and tend to have a shorter
      characteristic path length to their neighbors. We extend our network analysis to
      encompass transcriptional regulatory networks. Although transcription factors
      with many targets tend to be essential, surprisingly, we find that genes that are
      regulated by many transcription factors are usually not essential.

PMID- 15145575
TI  - Evidence against the selfish operon theory.
AB  - According to the selfish operon hypothesis, the clustering of genes and their
      subsequent organization into operons is beneficial for the constituent genes
      because it enables the horizontal gene transfer of weakly selected, functionally
      coupled genes. The majority of these are expected to be non-essential genes. From
      our analysis of the Escherichia coli genome, we conclude that the selfish operon
      hypothesis is unlikely to provide a general explanation for clustering nor can it
      account for the gene composition of operons. Contrary to expectations, essential
      genes with related functions have an especially strong tendency to cluster, even
      if they are not in operons. Moreover, essential genes are particularly abundant
      in operons.

PMID- 15145576
TI  - p53's double life: transactivation-independent repression of homologous
      recombination.
AB  - The tumor suppressor protein p53 controls cell cycle checkpoints and apoptosis
      via the transactivation of several genes. However, data from various laboratories
      suggest an additional role for p53: transcription-independent suppression of
      homologous recombination (HR). Genetic and physical interactions among p53, HR
      proteins (e.g. RAD51 and RAD54) and HR-DNA intermediates show that p53 acts
      directly on HR during the early and late steps of recombination. Complementary to
      the MSH2 mismatch-repair system, p53 appears to impair excess HR by controlling
      the minimal efficiency processing segment and by reversing recombination
      intermediates. By controlling the balance between the BLM and the RAD51 pathways,
      this direct role of p53 could maintain genome stability when replication forks
      are stalled at regions of DNA damage. In this article, we discuss the direct role
      of p53 on HR and the consequences for genome stability, tumor protection and
      speciation.

PMID- 15145577
TI  - DNA and histone methylation in plants.
AB  - Heritable patterns of gene activity and gene silencing arise by the formation and
      the propagation of specific chromatin states that restrict or permit gene
      expression. In mammals and in plants, restrictive heterochromatin is associated
      with the hypermethylation of DNA at CG sites and with the specific modification
      of histones, such as the methylation of histone H3 at lysine 9 (H3K9(Me)). In
      addition to CG methylation, plant nuclear DNA packaged in restrictive chromatin
      is also usually methylated in cytosines outside a CG sequence context. The
      functional relationship between an unexpectedly complex plant DNA-methylation
      system and histone modifications that lead to chromatin compaction and gene
      silencing is under intense scrutiny. The results of recent studies indicate
      intriguing links between chromatin remodeling, histone methylation, DNA
      methylation and RNA interference.

PMID- 15145578
TI  - Checks and balancers: balancer chromosomes to facilitate genome annotation.
AB  - Phenotype-driven mutagenesis screens are used to discover gene function in model
      organisms. Mutations that are induced by chemical mutagens can occur anywhere in
      the genome. However, the use of a balancer chromosome (where a phenotypically
      marked segment of a chromosome is inverted) in a mutagenesis screen enables
      mutations to be mapped in a defined region of the genome and maintained stably in
      a heterozygous state. Mouse balancer chromosomes can be engineered using Cre-loxP
      technology in selected regions of the genome. Balancer mutagenesis screens will
      provide a systematic functional analysis of the genes on mouse chromosomes, and
      consequently, will facilitate a functional annotation of the mammalian genome
      sequence.

PMID- 15145579
TI  - Messenger RNA stability in mitochondria: different means to an end.
AB  - Gene expression is regulated at many stages not merely at the level of
      transcription. Among the important post-transcriptional processes, RNA turnover
      has a crucial role. The stability of mRNA in the cytosol of eukarya is increased
      by the addition of a 3' poly(A) extension. By contrast, this process mediates
      rapid RNA decay in prokarya. How is mRNA turnover regulated in mitochondria?
      Their monophyletic, alpha-proteobacterial origin predicts that polyadenylation
      will induce rapid decay by nucleases and associated factors that are similar to
      their bacterial ancestors. In this article, however, we report that the
      regulation of mitochondrial mRNA turnover in diverse species is surprisingly
      different.

PMID- 15145580
TI  - Genome information resources - developments at Ensembl.
AB  - Genome information resources such as Ensembl manage and present DNA sequence and
      annotation arising from genome projects. Recent developments in the Ensembl
      system include access to inter-species comparisons at both the genomic and
      protein sequence levels and improvements to the display of polymorphism data.
      Users can now display their own data in the context of other annotation. In
      addition, a fast and flexible data retrieval system, EnsMart, has been developed.

PMID- 15145581
TI  - Heterotrophic plate count bacteria in drinking water: public health implications.
      Geneva, Switzerland, April 22-24, 2002. Symposium proceedings.

PMID- 15145582
TI  - Heterotrophic plate count measurement in drinking water safety management: report
      of an Expert Meeting Geneva, 24-25 April 2002.
AB  - A group of microbiology and public health experts including regulatory and
      medical expertise was convened in Geneva, Switzerland, 25-26 April 2002 to
      consider the utility of heterotrophic plate count (HPC) measurements in
      addressing drinking water quality and safety. The group was convened following
      the NSF International/World Health Organization Symposium on HPC Bacteria in
      Drinking Water--Public Health Implications? The Expert Meeting was attended by 31
      participants from Australia, Canada, France, Germany, Italy, Japan, the
      Netherlands, South Africa, Switzerland, UK and USA.

PMID- 15145583
TI  - Rare occurrence of heterotrophic bacteria with pathogenic potential in potable
      water.
AB  - Since the discovery of Legionella pneumophila, an opportunistic pathogen that is
      indigenous to water, microbiologists have speculated that there may be other
      opportunistic pathogens among the numerous heterotrophic bacteria found in
      potable water. The US Environmental Protection Agency (USEPA) developed a series
      of rapid in vitro assays to assess the virulence potential of large numbers of
      bacteria from potable water to possibly identify currently unknown pathogens.
      Results of surveys of potable water from several distribution systems using these
      tests showed that only 50 of the approximately 10,000 bacterial colonies
      expressed one or more virulence characteristics. In another study, 45 potable
      water isolates that expressed multiple virulence factors were tested for
      pathogenicity in immunocompromised mice. None of the isolates infected mice that
      were compromised either by treatment with carrageenan (CG), to induce
      susceptibility to facultative intracellular pathogens, or by cyclophosphamide
      (CY), to induce susceptibility to extracellular pathogens. These results indicate
      that there are very few potential pathogens in potable water and that the
      currently developed in vitro virulence screening tests give an overestimation of
      the numbers of heterotrophic bacteria that may be pathogens. Current efforts are
      focused on using the animal models to screen concentrated samples of waters known
      to contain large numbers of heterotrophic bacteria and newly discovered
      Legionella-like organisms that parasitize amoebae.

PMID- 15145584
TI  - Virulence and risk from drinking water of heterotrophic plate count bacteria in
      human population groups.
AB  - Bacteria are natural inhabitants of all aqueous environments. The heterotrophic
      plate count is a means of assessing the concentration of these bacteria in foods,
      water, and water filtration systems. Methods vary, but are designed to enumerate
      bacteria that have evolved an environmental lifestyle. Most commonly, low
      nutrient, low ionic strength culture media are employed. The group of
      environmental bacteria enumerated depends on the media formulation and incubation
      conditions but are commonly known as heterotrophic plate count (HPC) bacteria; in
      Europe, this group is also referred to as autochthonous flora. While HPC inhabit
      an environmental niche, there has been concern that at some concentration they
      may be a human health risk. A review of the literature, including animal and
      human feeding studies, analysis of virulence factors, and outbreaks demonstrates
      that HPC bacteria as enumerated on HPC culture media have not been established as
      a human health threat at any concentration in drinking water or foods.

PMID- 15145585
TI  - Heterotrophic plate count bacteria--what is their significance in drinking water?
AB  - While the literature documents the universal occurrence of heterotrophic plate
      count (HPC) bacteria in soils, foods, air, and all sources of water, there is a
      lingering question as to whether this group of organisms may signal an increased
      health risk when elevated populations are present in drinking water. This paper
      reviews the relevant literature on HPC bacteria in drinking water, the lack of
      clinical evidence that elevated populations or specific genera within the HPC
      flora pose an increased health risk to any segment of the population, and the
      appropriate uses of HPC data as a tool to monitor drinking water quality changes
      following treatment. It finds no evidence to support health-based regulations of
      HPC concentrations.

PMID- 15145586
TI  - Potentially pathogenic features of heterotrophic plate count bacteria isolated
      from treated and untreated drinking water.
AB  - Heterotrophic plate counts (HPCs) are commonly used to assess the general
      microbiological quality of drinking water. Drinking water quality specifications
      worldwide recommend HPC limits from 100 to 500 cfu ml(-1). A number of recent
      studies revealed evidence that these bacteria may not be as harmless as generally
      accepted. It appears that immuno-compromised individuals are particularly at
      risk. This would include the very young and very old patients with diseases such
      as AIDS and patients on therapy for purposes such as organ transplantation and
      cancer treatment. In this study, 339 bacterial colonies were isolated at random
      from selected treated and untreated drinking water in South Africa using routine
      heterotrophic plate count tests. In a first step to screen for potentially
      pathogenic properties, 188 (55.5%) of the isolates showed alpha- or beta
      haemolysis on human- and horse-blood agar media. Subsequent analysis of the
      haemolytic isolates for enzymatic properties associated with pathogenicity
      revealed the presence of chondroitinase in 5.3% of the isolates, coagulase in
      16.0%, DNase in 60.6%, elastase in 33.0%, fibrinolysin in 53.7%, gelatinase in
      62.2%, hyaluronidase in 21.3%, lecithinase in 47.9%, lipase in 54.8% and
      proteinase in 64.4%. Fluorescein and pyocyanin were not produced by any of the
      isolates. Among the haemolytic isolates, 77.7% were resistant to oxacillin 1
      microg, 59.6% to penicillin G 2 units, 47.3% to penicillin G 10 units, 54.3% to
      ampicillin 10 microg and 43.1% to ampicillin 25 microg. Cell culture studies
      revealed that 96% of haemolytic isolates were cytotoxic to HEp-2 cells, and 98.9%
      of the 181 cytotoxic isolates adhered to HEp-2 or Caco-2 cells. HEp-2 cells were
      invaded by 43.6%, and Caco-2 cells by 49.7%, of the 181 cytotoxic isolates. The
      invasion index on HEp-2 cells ranged from 1.9 x 10(-1) to 8.9 x 10(-6), whereas
      the invasion index on Caco-2 cells varied between 7.7 x 10(-2) and 8.3 x 10(-6).
      The most commonly isolated genera with these potentially pathogenic features were
      Aeromonas, Acinetobacter, Aureobacterium, Bacillus, Chryseobacterium,
      Corynebacterium, Klebsiella, Moraxella, Pseudomonas, Staphylococcus, Tsukamurella
      and Vibrio. The results obtained in this study support earlier findings on
      potentially pathogenic features of bacteria detected by routine HPCs on drinking
      water. These findings are in agreement with some epidemiological studies, which
      indicated an association between HPCs in drinking water and the incidence of
      gastroenteritis in consumers. However, the extent of the health risk concerned
      needs to be defined in more detail for meaningful revision of quality guidelines
      for HPCs in drinking water.

PMID- 15145587
TI  - Tracking the concentration of heterotrophic plate count bacteria from the source
      to the consumer's tap.
AB  - The goal of this project was to quantify the concentration of heterotrophic plate
      count (HPC) bacteria within water reaching consumer's taps, and from the sources
      used by a major utility serving the City of Tucson, AZ. With this information,
      the amounts and sources of HPC bacteria consumed at the tap could be determined.
      Samples of water were collected on a monthly basis from two well fields, the
      CAVSARP recovery well field and Southern Avra Valley well field which serves as
      one of the groundwater sources for Tucson, AZ, and the distribution system which
      serves the same homes from which tap water was also tested. The average
      concentration of HPC in source waters within Southern Avra Valley Wells was 56
      CFU/ml (range 1-1995/ml). From the CAVSARP recovery well field, corresponding
      values were 38 CFU/ml (1 to 502 CFU/ml). Unblended groundwater in the chlorinated
      distribution system averaged 22 CFU/ml (range 1-794). Blended water at the
      chlorinated distribution site averaged 47 CFU/ml (range 10-158). There was a
      major shift in the percentage of gram negative to gram-positive bacteria from the
      wells to the distribution system, to the tap. In the surface CAP source water,
      76% of the bacteria were gram-negative compared to 27% gram-negative in the
      CAVSARP recovery wells. In contrast, Avra Valley wells contained 17% gram
      negative bacteria. In both the Tucson groundwater distribution sites and blended
      distribution sites, the corresponding number of gram negative bacteria was 12%.
      Finally at the tap, only 0.2% of the bacteria were gram-negative. The average
      number of bacteria in household taps averaged 3072 HPC/ml and was equal or
      greater than 500 ml 68% of the time. This study shows that the number of HPC
      bacteria increases dramatically from the distribution system to the consumers
      tap. Thus, the major source of bacteria ingested by the average consumer in
      Tucson originates from bacteria within the household distribution system or the
      household tap, rather than from source waters or the distribution system. It is
      also clear that consumers' regularly consume more than 500 HPC/ml from drinking
      water taken from the household tap.

PMID- 15145588
TI  - Heterotrophic plate count monitoring of treated drinking water in the UK: a
      useful operational tool.
AB  - The count of general or heterotrophic bacterial populations in treated drinking
      water in the UK has been undertaken since the 1880s. Counts of heterotrophic
      bacteria at 22 and 37 degrees C are used widely as part of an overall assessment
      of treated drinking water quality. There were no legislated standards for water
      quality in the UK until adoption of the first EU Directive in 1989. The UK has,
      however, never stipulated numerical standards or guidelines for heterotrophic
      bacteria, although their enumeration has long been part of the assessment of
      'wholesome' water, on which advice regarding microbiological quality was given in
      a series of documents known as 'Report 71'. The current regulations stipulate
      only that there should be 'no abnormal change' in numbers normally associated
      with a given supply. This paper reviews the historical context regarding the
      enumeration, and interpretation of results, of heterotrophic bacteria from
      treated drinking water, and information regarding current practices by UK water
      suppliers. The appropriateness of using heterotrophic bacteria counts as an
      operational tool or as a health parameter is briefly discussed in the light of
      the UK experience.

PMID- 15145589
TI  - Heterotrophic plate count methodology in the United States.
AB  - In the United States (US), the history of bacterial plate counting (BPC) methods
      used for water can be traced largely through Standard Methods for the Examination
      of Water and Wastewater (Standard Methods). The bacterial count method has
      evolved from the original Standard Methods (1st edition, 1905) plate count which
      used nutrient gelatin and incubation at 20 degrees C for 48 h, to the HPC method
      options in the latest edition of Standard Methods that provide greater
      flexibility of application, depending on the data needs of the water analyst. The
      use of agar-agar as a gelling agent, replacing gelatin, allowed the use of higher
      incubation temperatures and resulted in the "body temperature count" (37 degrees
      C) found in the 3rd through the 8th edition of Standard Methods. The change from
      37 degrees C incubation to 35+/-0.5 degrees C accommodated laboratories that did
      both milk and water analyses. By using a single temperature, fewer incubators
      were needed. The term "standard plate count" (SPC) first appeared in 1960 (11th
      edition) along with plate count agar. Incubation at 20 degrees C for the plate
      count was dropped from the 13th to 15th editions and few changes were made in the
      SPC method from the 11th edition through the 13th editions. Plate count analysis
      of bottled waters was included in the 14th edition (1975), calling for incubation
      at 35+/-0.5 degrees C for 72+/-4 h. Perhaps the most significant changes in plate
      count methods occurred with the 16th edition (1985). The term heterotrophic plate
      count replaced the standard plate count, and the spread plate (SP) and membrane
      filter (MF) methods were added along with new media for pour and spread plates
      (R2A agar and NWRI agar, both low nutrient) and for the membrane filter method
      (mHPC medium). The use of low nutrient media, lower incubation temperature, and
      longer incubation times, results in higher plate count results for most water
      samples. The options currently available, including low and high nutrient media,
      incubation temperatures (20 degrees C, 28 degrees C or 35 degrees C), plating
      methods (pour plate (PP), spread plate and membrane filter) and range of
      incubation times (24, 48, 72 h and 5-7 days) provide great flexibility in the
      application of the HPC analysis to drinking water.

PMID- 15145590
TI  - Establishment of HPC(R2A) for regrowth control in non-chlorinated distribution
      systems.
AB  - Drinking water distributed without disinfection and without regrowth problems for
      many years may show bacterial regrowth when the residence time and/or temperature
      in the distribution system increases or when substrate and/or bacterial
      concentration in the treated water increases. An example of a regrowth event in a
      major German city is discussed. Regrowth of HPC bacteria occurred unexpectedly at
      the end of a very hot summer. No pathogenic or potentially pathogenic bacteria
      were identified. Increased residence times in the distribution system and
      temperatures up to 25 degrees C were identified as most probable causes and the
      regrowth event was successfully overcome by changing flow regimes and decreasing
      residence times. Standard plate counts of HPC bacteria using the spread plate
      technique on nutrient rich agar according to German Drinking Water Regulations
      (GDWR) had proven to be a very good indicator of hygienically safe drinking water
      and to demonstrate the effectiveness of water treatment. However, the method
      proved insensitive for early regrowth detection. Regrowth experiments in the lab
      and sampling of the distribution system during two summers showed that spread
      plate counts on nutrient-poor R2A agar after 7-day incubation yielded 100 to 200
      times higher counts. Counts on R2A after 3-day incubation were three times less
      than after 7 days. As the precision of plate count methods is very poor for
      counts less than 10 cfu/plate, a method yielding higher counts is better suited
      to detect upcoming regrowth than a method yielding low counts. It is shown that
      for the identification of regrowth events HPC(R2A) gives a further margin of
      about 2 weeks for reaction before HPC(GDWR).

PMID- 15145591
TI  - Rapid and automated detection of fluorescent total bacteria in water samples.
AB  - Traditional methods for the detection and enumeration of bacteria in water
      samples are growth-based and require several days to obtain the result. New
      techniques which reduce the time of analysis have been developed. The objective
      of this work was to test a rapid method for the detection and enumeration of
      total viable bacteria using direct fluorescent labelling and detection by laser
      scanning. This method (referred to as TVC for Total Viable Count) was compared to
      the R2A culture method and the cyano-ditolyl-tetrazolium chloride (CTC) staining
      method for the analysis of samples before the final chlorination (after GAC
      filtration) and drinking water samples. For the comparison of TVC and CTC, the
      outcome depends on the water type: for samples after GAC filtration, TVC counts
      were significantly lower than CTC counts by up to 2 log10 orders of magnitude.
      For chlorinated water samples, TVC counts were not significantly different from
      CTC counts. The comparison of TVC and R2A showed that TVC counts could be lower
      than R2A counts or equivalent depending on the type of water. For drinking water,
      the TVC method proved to yield results equivalent to those of the R2A method. The
      TVC method requires much shorter time frame than others. It is also simple to use
      and allows the analysis of large volumes (100 ml) of drinking water.

PMID- 15145592
TI  - Eubacterial 16S-rDNA amplicon profiling: a rapid technique for comparison and
      differentiation of heterotrophic plate count communities from drinking water.
AB  - Determination of the heterotrophic plate count (HPC) is commonly used as a
      surrogate to assess the general microbial water quality in drinking water. For
      routine monitoring applications, the HPC is investigated in a quantitative way.
      However, qualitative data about the HPC bacterial community composition and/or
      population dynamics are required for particular situations. In order to provide
      fast and efficient qualitative approaches, molecular biological DNA profiling
      techniques seem to be suitable tools for the analysis of the total HPC community
      composition. In this work a DNA profiling technique is presented, which was
      recently demonstrated by our group to have potential for the rapid qualitative
      comparison and differentiation of HPC communities from raw and drinking water.
      The presented approach consists of a polymerase chain reaction (PCR)-based
      denaturing gradient gel electrophoresis (DGGE) for the generation of 16S-rDNA
      amplicon fingerprints from whole HPC community DNA extracts. In the context of
      this proceeding, the methodical background is presented and possible scientific
      merits as well as potential water management applications are discussed. Selected
      examples of (i) the demonstration of selective growth of HPC populations on
      different media and the comparison to the total in situ drinking water
      eubacterial community, (ii) the screening for HPC community variations at
      different locations of a drinking water distribution system, and (iii) the
      influence assessment on groundwater HPC communities by an infiltrating treated
      sewage effluent (bacterial source tracking) are given.

PMID- 15145593
TI  - Understanding the distribution system as a bioreactor: a framework for managing
      heterotrophic plate count levels.
AB  - It is important to manage the level of heterotrophic plate count (HPC) bacteria
      in drinking water. Since the vast majority of HPCs measured in the distribution
      system are normally actually produced there, managing HPC numbers implies
      managing the distribution system as a bioreactor. This paper proposes a new
      concept, the HPC Production Index (HPI), which is the ratio of HPC production in
      a given distribution system to that produced by an essentially biostable water
      entering that same system. HPI is related to various physical, chemical and water
      quality factors such as contact time, disinfectant residual and level of
      biodegradable organic matter, which affect the performance of the distribution
      system as a bioreactor. HPI therefore provides a conceptual framework for
      managing distribution system HPC levels.

PMID- 15145594
TI  - Involvement of humic substances in regrowth.
AB  - There appear to be interactions in the distribution system that complicate the
      ability to use AOC/BDOC as an independent assessment of regrowth potential. Two
      such complications are the limitation of the assays themselves and the potential
      interaction between the organic carbon concentration with the presence of
      disinfectants and pipe materials. To address these interactions, a series of
      experiments spanning several years have been conducted in model distribution
      systems at the Center for Biofilm Engineering (CBE) using soil-derived humics.
      When compared to easily utilized organics, humic substances supported the same
      order of magnitude of biofilm organisms. As carbon concentration was increased
      from 500 to 1000 to 2000 ppb, there was no increase in growth rate of the
      organisms, suggesting zero-order kinetics. If the system was chlorinated, there
      was less biomass, but growth rates were higher. In the presence of corrosion
      products, humic-fed systems supported more organisms than a control system fed
      biologically treated water. When free chlorine was maintained at a residual of
      about 0.2 mg/l, biofilm numbers on the surfaces were reduced. Phosphate alone did
      not result in fewer bacteria, while a combination of chorine and phosphate had
      the best results (lowest biofilm numbers). Adjustment to pH 9 was not effective.
      Recently completed work compared increasing levels of humic substances in the
      presence of free chlorine and monochloramine on biofilm growth on a number of
      surfaces (PVC, epoxy, cement, ductile iron). As the concentration of humic
      substances was increased from 0, 0.5 to 2 mg/l, there was an increase in biofilm
      numbers on all surfaces. This effect was the most pronounced on iron surfaces.
      These results illustrate that carbon compounds not measured by the BDOC or AOC
      tests may profoundly influence biofilm numbers. In addition, iron surfaces are at
      much higher risk for elevated biofilm counts in the presence of humic substances,
      even if disinfection is practiced. However, corrosion control may mitigate this
      interaction.

PMID- 15145595
TI  - Heterotrophic plate count and consumer's health under special consideration of
      water softeners.
AB  - The phenomenon of bacterial growth in water softeners is well known since years.
      To upgrade the hygienic safety of water softeners, the German DIN Standard 19636
      was developed, to assure that the distribution system could not be contaminated
      by these devices and that the drinking water to be used in the household still
      meets the microbiological standards according to the German drinking water
      guidelines, i.e. among others heterotrophic plate count (HPC) below 100 CFU/ml.
      Moreover, the standard for the water softeners includes a test for contamination
      with Pseudomonas aeruginosa which has to be disinfected during the regeneration
      phase. This is possible by sanitizing the resin bed during regeneration by
      producing chlorine. The results of the last 10 years of tests of water softeners
      according to DIN 19636 showed that it is possible to produce water softeners that
      comply with that standard. Approximately 60% of the tested models were accepted.
      P. aeruginosa is used as an indicator for potentially pathogenic bacteria being
      able to grow also in low nutrient conditions which normally prevail in drinking
      water. Like other heterotrophs, the numbers of P. aeruginosa increase rapidly as
      stagnation occurs. Normally P. aeruginosa is not present in the distributed
      drinking water. However, under certain conditions, P. aeruginosa can be
      introduced into the drinking water distribution system, for instance, during
      construction work. The occurrence of P. aeruginosa is shown in different cases in
      treatment plants, public drinking water systems and in-house installations. The
      compliance with DIN 19636 provides assurance that a water softener will not be a
      constant source of contamination, even if it is once inoculated with a
      potentially pathogenic bacterium like P. aeruginosa.

PMID- 15145596
TI  - Assessment of the microbial integrity, sensu G.S. Wilson, of piped and bottled
      drinking water in the condition as ingested.
AB  - The second half of the 20th century witnessed substantial progress in the
      assurance and verification of microbiological integrity, i.e., safety and sensory
      quality, of drinking water. Enteropathogenic agents, such as particular viruses
      and protozoa, not previously identified as transmitted by industrially provided
      water supplies, were demonstrated to cause disease outbreaks, when ingested with
      piped water. The potential harm posed by carry-over of orally toxic metabolites
      of organisms, producing 'algal' (cyanophytic) blooms, was considered. In
      addition, earlier observations on the colonization of attenuated drinking water
      bodies by a variety of oligotrophic Gram-negative bacteria were confirmed and
      extended. This new evidence called for updating both water purification
      technologies and analytical methodology, serving to verify that goals had been
      attained. For the former purpose, the hazard analysis empowering control of
      critical practices (HACCP) strategy, introduced about 1960 in industrial food
      processing, was successfully adopted. Elimination, devitalization or barrier
      technologies for the more recently identified water-borne pathogens were
      elaborated, taking account of the hazard of production of chlorinated compounds
      with alleged adverse health effects. Biofilm formation throughout water
      distribution networks was brought under control by strict limitation of
      concentrations of compounds, assimilable by oligotrophic bacteria. Upon
      acknowledging that direct detection tests for pathogens were futile, because of
      their most sporadic and erratic distribution, Schardinger's marker organism
      concept was anew embraced, rigorously revised and substantially enlarged.
      Misleading designations, like searches for 'faecal coliforms' were replaced by
      boundary testing for Escherichia coli and appropriate Enterococcus spp. In
      addition, though still to be perfected, detection protocols for relevant
      bacteriophages or index viruses and, to a certain extent, also for spores of
      aerobic and anaerobic sporing rods were also elaborated. In all monitoring
      account was taken of sublethally injured target organisms, surviving purification
      technologies, though not deprived of their ecological significance. A need
      remains for a rigorously standardized operating procedure (SOP) for colony counts
      of psychrotrophic, oligotrophic Gram-negative rod-shaped bacteria ('heterotrophic
      plate count'), which constitute a useful criterion of indicator value. As in the
      contemporary HACCP approach to food safety, guidelines for assessing success or
      failure in control of integrity (Water Safety Objectives) were empirically
      elaborated. These rely on surveys on water samples, originating from drinking
      water supplies, previously verified as complying with longitudinally integrated
      HACCP-based purification technologies. Structured Academic dissemination of these
      innovations, through professional microbiologists to operator and executive
      levels, is recommended. Web based Distance Learning MSc Programmes, like the one,
      since the academic year 2003-2004, offered by the University of Hertfordshire,
      Hatfield, UK, may contribute to such endeavours. Though the complete Course is
      centered around Food Safety, the Modules in-Residence Practicals and Science and
      Technology of Drinking Water can be studied as an entity while being employed.

PMID- 15145598
TI  - In pneumococcal meningitis a novel water-soluble inhibitor of matrix
      metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury
      of the cerebral cortex.
AB  - Matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE)
      contribute to the pathophysiology of bacterial meningitis. To date, MMP
      inhibitors studied in models of meningitis were compromised by their hydrophobic
      nature. We investigated the pharmacokinetics and the effect of TNF484, a water
      soluble hydroxamate-based inhibitor of MMP and TACE, on disease parameters and
      brain damage in a neonatal rat model of pneumococcal meningitis. At 1 mg/kg q6h
      TNF484 reduced soluble TNF-alpha and the collagen degradation product
      hydroxyproline in the cerebrospinal fluid. Clinically, TNF484 attenuated the
      incidence of seizures and was neuroprotective in the cortex. Water-soluble MMP
      inhibitors may hold promise in the therapy of bacterial meningitis.

PMID- 15145599
TI  - Evidence of a protective effect of phosphatidylserine-containing liposomes on
      lipopolysaccharide-induced impairment of long-term potentiation in the rat
      hippocampus.
AB  - Lipopolysaccharide (LPS) has a negative impact on long-term potentiation (LTP) in
      the rat hippocampus, which has been correlated with increased concentration of
      interleukin-1 beta (IL-1 beta) and activation of p38 and c-Jun N-terminal kinase
      (JNK). It has been documented that phosphatidylserine (PS)-containing liposomes
      induce anti-inflammatory signals and we report that pre-treatment of rats with PS
      liposomes prevented these LPS-induced effects while also inhibiting microglial
      activation. We also observed increased concentration of the anti-inflammatory
      cytokine interleukin-10 (IL-10), whose intracerebroventricular injection
      administration mimicked the effects of PS liposomes on LTP. This suggests that
      administration of PS liposomes protects against the deleterious effects of LPS
      possibly through generation of the anti-inflammatory cytokine IL-10.

PMID- 15145600
TI  - Persistent immune activation associated with a mouse model of Staphylococcus
      aureus-induced experimental brain abscess.
AB  - We have established a mouse experimental brain abscess model using Staphylococcus
      aureus where lesion sites are greatly exaggerated compared to the localized area
      of initial infection, reminiscent of an overactive immune response. Here we
      demonstrate the prolonged expression of IL-1 beta, TNF-alpha, and macrophage
      inflammatory protein-2 (MIP-2/CXCL2), concomitant with a chronic disruption of
      the blood-brain barrier (BBB) in mice with S. aureus-induced brain abscess. These
      changes correlated with the continued presence of infiltrating neutrophils and
      macrophages/microglia. Collectively these findings suggest that the excessive
      tissue damage that often results from brain abscess may be mediated, in part, by
      the perpetuation of antibacterial immune responses that are not downregulated in
      a timely manner.

PMID- 15145602
TI  - Suppression of IgE production and modulation of Th1/Th2 cell response by
      electroacupuncture in DNP-KLH immunized mice.
AB  - Effects of electroacupuncture (EA) on Th1/Th2 cell response were investigated in
      BALB/c mice immunized intraperitoneally with 2,4-dinitrophenylated keyhole limpet
      protein (DNP-KLH). Successive electroacupuncture stimulation on the ST36 acupoint
      was performed just after immunization. Serum levels of antigen-specific IgE and
      total IgE were significantly decreased compared with non-acupunctured controls.
      Production of the Th2-specific cytokines IL-4 and IL-13 in the anti-CD3 mAb
      activated splenocytes was significantly suppressed in ST36 electroacupunctured
      mice compared with non-acupunctured mice. These results imply that successive
      electroacupuncture on ST36 can decrease the serum level of antigen-specific IgE
      and total IgE by suppression of the Th2 lineage development.

PMID- 15145601
TI  - Potent effect of interleukin-1 beta to evoke ATP and adenosine release from rat
      hippocampal slices.
AB  - In this study the effect of IL-1 beta on [(3)H]purine release from rat
      hippocampal slices was explored. IL-1 beta (3 x 10(-18)-3 x 10(-14) M)
      concentration-dependently elevated the basal [(3)H]purine efflux, and this effect
      was reversed by the selective IL-1RI receptor antagonist IL-1ra (10(-12) M). HPLC
      analysis revealed that the amount of [(3)H]ATP and [(3)H]adenosine significantly
      increased in the effluent in response to IL-1 beta. The sodium channel inhibitor
      tetrodotoxin, the NMDA and non-NMDA receptor antagonists d(-)-2-amino-5
      phosphonopentanoic acid (AP-5) plus 6-cyano-7-nitroquinoxaline-2,3-dione-disodium
      (CNQX) almost completely abolished IL-1 beta-evoked [(3)H]purine release. The
      effect of IL-1 beta on [(3)H]purine efflux was also prevented by the p38 MAP
      kinase inhibitor SB 203580, by the nucleoside transport inhibitor nitrobenzyl
      thioinosine (NBTI) and by low temperature (4 degrees C). In summary IL-1 beta
      triggers a transporter mediated [(3)H]purine efflux in the hippocampus which is
      conveyed by glutamate receptor activation and the p38 MAP kinase pathway, and
      could serve as a mediator of IL-1 beta-induced synaptic depression.

PMID- 15145603
TI  - Complement synthesis and activation in the brain of SIV-infected monkeys.
AB  - Complement is one of the most critical defence tools against cerebral infections,
      but uncontrolled complement biosynthesis and activation can induce profound brain
      tissue damage. To clarify the role of complement in the pathogenesis of AIDS
      associated neurological disorders, we analysed the synthesis of complement in the
      brains of SIV-infected rhesus macaques. Using immunohistochemical staining we
      could show that the cerebral synthesis of complement factors C1q and C3 was
      strongly upregulated in SIV-infected monkeys compared to the spontaneous
      synthesis in uninfected control monkeys. Astrocytes, neurons, microglia,
      infiltrating macrophages and multinuclear giant cells all contribute to the high
      amounts of C1q and C3 in the brain. Secreted C1q and C3 are also deposited on the
      membrane of neurons, a prerequisite for formation of the membrane-driven lytic
      membrane attack complex. The membrane deposition thus might suggest complement
      induced lysis of bystander neurons as a potential mechanism for cell damage
      during viral infection of the brain.

PMID- 15145605
TI  - Intranasal administration of interferon beta bypasses the blood-brain barrier to
      target the central nervous system and cervical lymph nodes: a non-invasive
      treatment strategy for multiple sclerosis.
AB  - Intranasal (i.n.) administration of IFN beta-1b was examined as a route for
      targeted delivery to the rat central nervous system (CNS). Intranasal
      administration resulted in significant delivery throughout the CNS and cervical
      lymph nodes with low delivery to peripheral organs. At similar blood levels,
      intravenous (i.v.) administration of IFN beta-1b yielded 88-98% lower CNS levels
      and 100-1650% greater peripheral organ levels compared to intranasal.
      Autoradiography confirmed much greater delivery to the CNS with intranasal
      administration. Intranasally administered IFN beta-1b reached the brain intact
      and produced tyrosine phosphorylation of IFN receptor in the CNS. Intranasal
      administration offers a non-invasive method of drug delivery for multiple
      sclerosis (MS) that bypasses the blood-brain barrier (BBB) and directly targets
      the CNS and lymph nodes.

PMID- 15145604
TI  - Pixantrone (BBR2778) reduces the severity of experimental allergic
      encephalomyelitis.
AB  - Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX)
      as an antineoplastic drug. In our study, pixantrone reduced the severity of acute
      and decreased the relapse rate of chronic relapsing experimental allergic
      encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+,
      CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with
      both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell
      proliferation tests of human and rodents cells evidenced that pixantrone was
      effective at concentrations which can be effectively obtained after i.v.
      administration in humans. Cardiotoxicity was present only in MTX-treated rats.
      The effectiveness and the favorable safety profile makes pixantrone a most
      promising immunosuppressant agent for clinical use in multiple sclerosis (MS).

PMID- 15145606
TI  - Expression of osteopontin and its ligand, CD44, in the spinal cords of Lewis rats
      with experimental autoimmune encephalomyelitis.
AB  - The expression of osteopontin (OPN) and one of its ligands, CD44, was studied in
      the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE).
      Western blot analysis showed that osteopontin significantly increased at the
      early and peak stage of EAE and slightly declined thereafter. Osteopontin was
      constitutively expressed in some astrocytes adjacent to pia mater and neurons in
      normal rats, and was shown to be increased in the same cells and also in some
      inflammatory cells including macrophages at the early and peak stage of EAE.
      CD44, a ligand for osteopontin, was constitutively expressed in astrocytes in
      normal and control spinal cords and was also expressed in inflammatory cells, as
      well as increased expression in astrocytes in EAE. These findings suggest that
      inflammatory cells as well as reactive astrocytes are major sources of
      osteopontin in rat EAE, and osteopontin may interact with its ligand CD44 on
      astrocytes and inflammatory cells in EAE, possibly mediating autoimmune central
      nervous system (CNS) diseases in rats.

PMID- 15145607
TI  - Sodium butyrate suppresses interferon-gamma-, but not lipopolysaccharide-mediated
      induction of nitric oxide and tumor necrosis factor-alpha in microglia.
AB  - In the present study, we demonstrate that sodium butyrate repressed IFN-gamma
      induced expression of iNOS and TNF-alpha, but had little effect on LPS-induced
      expression in BV2 murine microglial cells. Sodium butyrate significantly
      inhibited NF-kappa B binding and NF-kappa B-mediated transcription induced by IFN
      gamma, suggesting that the anti-inflammatory effect of sodium butyrate is
      mediated via specific inhibition of the NF-kappa B pathway. IFN-gamma is a major
      stimulator of innate and adaptive immune response. Thus, the specific down
      regulation of IFN-gamma-induced microglial activation by sodium butyrate may
      provide potential therapeutic strategies for a variety of inflammatory diseases
      in the central nervous system.

PMID- 15145608
TI  - Limited repertoire of HLA-DRB1*0401-restricted MBP111-129-specific T cells in HLA
      DRB1*0401 Tg mice and their pathogenic potential.
AB  - Since myelin basic protein (MBP)111-129 is an immunodominant epitope in humans
      carrying HLA-DRB1*0401, we investigated the encephalitogenic potential of HLA
      DRB1*0401-restricted MBP111-129-specific T cells using HLA-DRB1*0401/DRA*0101
      transgenic (Tg) mice. Although we could not detect the primary recall response to
      MBP111-129 peptide after immunization of HLA-DRB1*0401/DRA*0101 Tg mice with
      human MBP, V beta 10(+) and V beta 2(+) HLA-DRB1*0401-restricted MBP111-129
      specific T cells proliferated after restimulation of the lymph node cells with
      human MBP111-129 in vitro. The V beta 2(+) T cell line recognized only human
      MBP111-129 in the context of HLA-DRB1*0401, while the V beta 10(+) T cell line
      recognized both the human and murine MBP111-129 epitopes. Therefore, we examined
      the encephalitogenic potential of the V beta 10(+) T cell line in HLA
      DRB1*0401/DRA*0101 Tg mice by adoptive transfer experiments. The V beta 10(+) T
      cell line induced mild EAE and inflammatory lesions were observed in the spinal
      cord and the brainstem. In the spinal cord, the inflammation was observed in the
      peripheral nerve roots as well as in the CNS. These data suggest the pathogenic
      potential of HLA-DRB1*0401-restricted MBP111-129-specific T cells in humans.

PMID- 15145609
TI  - Alterations in chemokine expression following Theiler's virus infection and
      restraint stress.
AB  - Restraint stress (RS) applied to mice during acute infection with Theiler's virus
      causes corticosterone-induced immunosuppression. This effect was further
      investigated by measuring chemokine changes in the spleen and central nervous
      system (CNS) using an RNase Protection Assay. mRNAs for lymphotactin (Ltn),
      interferon-induced protein-10 (IP-10), MIP-1 beta, monocyte chemoattractant
      protein-1 (MCP-1) and TCA-3 were detected in the spleen at day 2 pi, but not in
      the brain of CBA mice infected with Theiler's virus. Ltn, IP-10 and RANTES were
      elevated in both the spleen and the brain at day 7 pi, and were significantly
      decreased by RS in the brain. RS also resulted in decreased inflammation within
      the CNS.

PMID- 15145610
TI  - TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive
      inflammation.
AB  - VCAM-1 is an adhesion molecule that is important to leukocyte movement across the
      blood-brain barrier and is involved in the formation of destructive CNS
      inflammatory lesions in experimental autoimmune encephalomyelitis (EAE) and
      multiple sclerosis (MS). We examined VCAM-1 expression in the CNS of animals with
      passively induced EAE and found abundant expression not only on the CNS
      endothelium but also on astrocytes. We show that tumor necrosis factor receptor-1
      (TNFR1) signaling is required for VCAM-1 expression by astrocytes, not the
      vascular endothelium. In addition, we demonstrate that VCAM-1 expression by
      astrocytes is crucial for T cell entry into the CNS parenchyma and is required
      for manifestation of neurological disease.

PMID- 15145611
TI  - Activated natural killer cells adhere to cultured hippocampal neurons and affect
      the dendritic morphology.
AB  - To examine the manner of interactions between immune cells and central nervous
      system (CNS) neurons, mouse hippocampal neurons were co-cultured with lymphokine
      (IL-2)-activated killer (LAK) cells. Immunocytochemical and time-lapse
      observations indicated that LAK cells migrated along neuronal processes and made
      adhesive contacts with them. In addition to the direct physical effects, LAK
      cells released glutamate, induced the formation of beads-like structure in the
      dendrites of about 14% of hippocampal neurons and caused the reduction of
      dendritic protrusions. These results suggest that infiltrating immune cells can
      form direct adhesive connections with CNS neurons and affect their dendritic
      morphology.

PMID- 15145612
TI  - Beta 2-adrenergic receptor agonist induces IL-18 production without IL-12
      production.
AB  - Endogenous catecholamine, epinephrine and norepinephrine, and isoproterenol
      concentration-dependently induced the production of interleukin (IL)-18, tumor
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inhibited that of IL
      10 in human peripheral blood mononuclear cells (PBMC). All responses by these
      stimulations were antagonized by the selective beta 2-adrenergic receptor (AR)
      antagonist, butoxamine, but not by alpha 1-, alpha 2- and beta 1-AR antagonists.
      The selective beta 2-AR agonists, salbutamol and terbutaline, induced a similar
      pattern of cytokine production, indicating that the effect of these AR agonists
      on cytokine production was through beta 2-AR stimulation. Anti-IL-18 Ab or
      caspase-1 inhibitor prevented all increase/decrease effects, suggesting that IL
      18 might affect the production of all other cytokines. While endogenous IL-18
      produced by salbutamol and terbutaline reached a sufficient concentration to
      induce IL-12 production, these beta 2-AR agonists did not induce the production
      of IL-12 at all. Epinephrine/norepinephrine/isoproterenol/beta 2-AR agonists
      increased the production of IL-18 in monocytes, but had no effect on IL-12, TNF
      alpha, IFN-gamma and IL-10 production. The lack of beta 2-AR-induced effect on IL
      12 production was due to a beta 2-AR-induced inhibition of an IL-18-elicited
      upregulation of both CD40 and CD40 ligand (CD40L/CD154) expressions on monocytes.
      The sympathetic innervating lymphoid organs may be under the control of beta2-AR
      stimulation, maintaining the basal cytokine environment in the tissues.

PMID- 15145613
TI  - Catecholaminergic control of NK cell cytolytic activity regulatory factors in the
      spleen.
AB  - We examined the effects of norepinephrine (NE), isoproterenol (ISO) and
      metaproterenol (MP) on natural killer (NK) cell cytolytic activity and on the
      protein and mRNA levels of the regulatory factors perforin and granzyme B and
      interferon-gamma (IFN-gamma) in splenocytes. NE, the beta-adrenergic agonist ISO,
      and the beta 2-selective-agonist MP all inhibited the protein and mRNA levels of
      perforin, granzyme B and mRNA levels of IFN-gamma. NE inhibited NK cell cytolytic
      activity as well. Furthermore, MP inhibition of granzyme B mRNA was blocked by
      the beta-antagonist nadolol. These data suggest that NE and beta-adrenergic
      agonists may inhibit NK cell cytolytic activity by regulating the production of
      perforin, granzyme B, and IFN-gamma in splenocytes.

PMID- 15145614
TI  - Gene-expression profiling of the early stages of MOG-induced EAE proves EAE
      resistance as an active process.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte
      glycoprotein (MOG) is a well-established animal model of multiple sclerosis (MS)
      in rodents. It reflects the wide spectrum of disease pathology and serves as a
      valuable tool for studying the pathogenesis and for testing new therapies of MS.
      In order to identify genes responsible for resistance to and modulation of the
      disease, we compared the mRNA expression profile of more than 12,000 genes by DNA
      microarray technique in lymph nodes of the highly EAE-susceptible mouse strain
      C57Bl/6 (B6) and the resistant strain C57Bl/10.S (B10). The disease onset in B6
      mice was day 15. We identified 84 genes that were up-regulated more than two-fold
      in B10 mice compared to vehicle-treated controls, whereas only two genes were up
      regulated in B6 mice after 7 and 15 days post-immunization (p.i.), respectively.
      We were able to match five up-regulated genes in B10 mice to known quantitative
      trait loci (QTLs), which control for EAE susceptibility. Only 17, respectively 5,
      genes were down-regulated at both time points in B10 and B6 mice. Tests for
      immunoreactivity to MOG (T cell proliferation and interferon-gamma (IFN-gamma)
      secretion) revealed no stronger immune response in B6 compared to B10 mice
      supporting the hypothesis of an immunosuppressive effect as a target to prevent
      EAE in the B10 mice. We conclude that resistance to EAE (and possibly to MS) is
      an active process mediated by multiple genes up-regulated in peripheral lymphatic
      organs of resistant animals. Thus, monitoring of the expression of these new
      candidate genes may serve as a tool for the disease progression and the
      pharmaceutical treatment.

PMID- 15145615
TI  - Inducible nitric oxide synthase in chronic active multiple sclerosis plaques:
      distribution, cellular expression and association with myelin damage.
AB  - Inducible nitric oxide synthase (iNOS) is an enzyme that produces nitric oxide
      (NO) and is thought to contribute to the pathogenesis of multiple sclerosis (MS).
      The extent of iNOS expression was examined using laser scanning confocal
      microscopy of 13 chronic active plaques from seven MS patients displaying both
      acute demyelination and active inflammation. iNOS expression in these plaques was
      substantial and diverse in cellular distribution. Expression of iNOS was observed
      in ependymal cells located in periventricular lesions, inflammatory cells, and
      occasionally in astrocytes. iNOS was found in microglial/macrophage cells that
      expressed CD64, the high affinity Fc gamma receptor associated with cells that
      have phagocytic function and participate in antibody-dependent cellular
      cytotoxicity (ADCC). Scavenger microglial/macrophage cells that expressed the
      marker CD14 were also present and may express iNOS. The markers for myelin
      damage, nitrotyrosine (an index of iNOS mediated damage via peroxynitrite
      formation), along with MBP fragments, were also observed associated with iNOS in
      MS plaques. Together, these findings support a central role for iNOS in the
      pathogenesis of multiple sclerosis.

PMID- 15145616
TI  - Corticosteroid resistance in a subpopulation of multiple sclerosis patients as
      measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production.
AB  - We assessed corticosteroid sensitivity in multiple sclerosis (MS) patients
      compared to control subjects, using an in vitro assay of dexamethasone (Dex)
      inhibition of lipopolysaccharide (LPS) stimulated-blood interleukin-6 production.
      Significantly higher concentrations of dexamethasone were needed to obtain 50%
      inhibition (ID(50)) of in vitro LPS stimulated interleukin (IL)-6 production
      (28.4 x 10(-7) M) in relapsing-remitting MS (RRMS) patients compared to chronic
      progressive MS (CPMS) patients (6.2 x 10(-7) M) or compared to controls (3.0 x
      10(-7) M). We also found a trend towards worsening of clinical status over time
      with increasing corticosteroid resistance. These data suggest that corticosteroid
      sensitivity may be a factor in the pathogenesis and could be used for prognosis
      of MS.

PMID- 15145617
TI  - Th1/Th2 balance and HTLV-I proviral load in HAM/TSP patients treated with
      interferon-alpha.
AB  - We studied the immunological and virological effects of interferon-alpha (IFN
      alpha) therapy in nine patients with HTLV-I-associated myelopathy (HAM/TSP).
      After therapy, the percentages of CCR5+ cells in CD4+ cells significantly
      decreased in the cerebrospinal fluid as well as blood. The therapy also
      significantly lowered the intracellular IFN-gamma+/interleukin-4+ T-cell ratio in
      blood. Those helper T-cell type 1 (Th1)-related responses tended to be higher and
      reduce more evidently following therapy in three patients who clinically
      improved. Also, all the three patients had one or more HTLV-I copies in five
      blood mononuclear cells. These results suggest that IFN-alpha suppresses Th1
      responses in HAM/TSP and that the patients with higher Th1 immunity and proviral
      loads may be responders of the therapy. Larger-scale studies are needed to
      confirm the findings.

PMID- 15145618
TI  - Interferon-gamma produced by encephalitogenic cells induces suppressors of
      cytokine signaling in primary murine astrocytes.
AB  - Suppressors of cytokine signaling (SOCS) are proteins that modulate cytokine
      responses in lymphoid cells. In these studies, cultured primary mouse astrocytes
      expressed SOCS-3 mRNA constitutively. Treatment with interferon-gamma (IFN-g)
      induced SOCS-1 and enhanced SOCS-3 expression, and was associated with decreased
      tumor necrosis factor-alpha (TNF) and increased leukemia inhibitory factor (LIF)
      in culture supernatants. Treatment with conditioned medium from myelin basic
      protein-stimulated encephalitogenic lymphoid cells (MBP-CM) increased SOCS-3 and
      induced SOCS-1 expression. The effects were largely due to IFN-g in MBP-CM, as
      anti-IFN-g antibody diminished induction. These findings suggest a role for IFN-g
      induced SOCS expression in regulation of CNS inflammatory responses by
      astrocytes.

PMID- 15145619
TI  - Temporal order of nonlinear dynamics in human brain.
AB  - In previous spectral analysis investigations, we demonstrated that the
      spontaneous activity of the alpha EEG is not stationary but rather shows cyclic
      alterations with a circa 1-min periodicity. Following the conclusion that a power
      increase in the alpha band implies a neuronal synchronization, and vice versa, an
      associated decrease of the EEG complexity was postulated. Accordingly, a rhythmic
      variation, i.e., a temporal order of the nonlinear dynamics with similar period
      length, was expected. Bipolar 4-min EEG recordings were obtained from 20 awake
      subjects (mean age: 23.5+/-2.5 years) with eyes closed for the EEG leads C3, C4,
      Oz, and Fz according to the 10-20 system. For the automatic evaluation of
      spontaneous alterations of complexity, a sliding computation of the so-called
      correlation dimension, using an analysis window length of 20 s continuously
      shifted by 1 s, was performed. The time series of complexity exhibited an
      oscillatory behavior with a mean period length of 58.7 s; the Friedman test
      statistic revealed no significant topological differences. For the rejection of
      the null hypothesis that the observed periodicity is a random one, two-group t
      tests and ANOVA with repeated measures were performed, comparing the
      corresponding amplitudes and period lengths with those derived from 20 pseudo
      random signals (taken from a multivariate Gaussian normal distribution). The mean
      relative change of EEG complexity was highly significantly increased (P<0.0001)
      compared to that of random data. Likewise, the difference of mean period lengths
      was also significant (P<0.01). The results indicate that the coupling strength of
      the neural network of the brain changes periodically, with a cyclic alteration
      from a central to a parallel processing mode of information, reflecting state
      transitions from synchronized, low-complex EEG activity to desynchronized high
      complex activity, and vice versa. Various neuronal control mechanisms that may be
      acting as pacemakers responsible for the temporal order of such transients are
      discussed. A disturbance of the temporal order may be of pathophysiological
      significance.

PMID- 15145620
TI  - Lateralization of amygdala activation: a systematic review of functional
      neuroimaging studies.
AB  - Functional neuroimaging studies of emotion processing consistently report
      amygdala activation. Most of these studies observed lateralized amygdala
      activity, indicative of a clear hemisphere-specific processing difference between
      the left and right amygdalae. Because individual studies use varying paradigms
      and are limited by statistical power and sensitivity, it has remained unclear
      whether the left or the right amygdala is more consistently involved in emotional
      processing. By combining results across 54 fMRI and PET studies in a
      metaanalysis, we sought to establish if a common pattern of lateralized amygdala
      activation exists. Our findings indicate that across studies, the left amygdala
      is more often activated than the right amygdala, suggesting different roles for
      the left and right amygdalae in emotional processing. Further analysis showed
      that this predominant left amygdala activation is not significantly related to
      stimulus type, task instructions, differential habituation rates of the left and
      right amygdalae or elaborate processing. The results are discussed in relation to
      methodological and theoretical issues regarding functional brain asymmetry.

PMID- 15145621
TI  - Critical role of brain-derived neurotrophic factor in mood disorders.
AB  - The purpose of this review is to integrate what is currently known about the role
      of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood
      disorders including major depressive disorder (MDD) and bipolar disorder (BD). We
      reviewed the pre-clinical and clinical papers demonstrating that BDNF plays a
      role in the pathophysiology of mood disorders and in the mechanism of action of
      therapeutic agents. Pre-clinical studies suggest that the expression of BDNF
      might be a downstream target of antidepressant treatments and mood stabilizers
      such as lithium and valproate, and that BDNF exerts antidepressant activity in
      animal models of depression. Furthermore, BDNF protects against stress-induced
      neuronal damage, and it might affect neurogenesis in the hippocampus, which is
      thought to be involved in the pathogenesis of mood disorders. Clinical studies
      have demonstrated that serum levels of BDNF in drug-naive patients with MDD are
      significantly decreased as compared with normal controls, and that BDNF might be
      an important agent for therapeutic recovery from MDD. Moreover, recent findings
      from family-based association studies have suggested that the BDNF gene is a
      potential risk locus for the development of BD. These findings suggest that BDNF
      plays a critical role in the pathophysiology of mood disorders and in the
      activity of therapeutic agents in patients with mood disorders. New agents
      capable of enhancing BDNF levels may lead aid the development of novel
      therapeutic drugs for patients with mood disorders.

PMID- 15145622
TI  - Oligodendrocyte myelin glycoprotein (OMgp): evolution, structure and function.
AB  - The oligodendrocyte myelin glycoprotein (OMgp) is a glycosylphosphatidylinositol
      anchored protein expressed by neurons and oligodendrocytes in the central nervous
      system (CNS). Although the precise function of OMgp is yet to be determined in
      vivo, recent in vitro studies suggested roles for this protein in both the
      developing and adult central nervous system. In vitro experiments demonstrated
      the participation of OMgp in growth cone collapse and inhibition of neurite
      outgrowth through its interaction with NgR, the receptor for Nogo. This function
      requires its leucine-rich repeat domain, a highly conserved region in OMgp during
      mammal evolution. OMgp leucine-rich repeat domain is also implicated in the
      inhibition of cell proliferation. Based on its developmental expression,
      localization and structure, OMgp may also be involved in the formation and
      maintenance of myelin sheaths. Cell proliferation, neuronal sprouting and
      myelination are crucial processes involved in brain development and regeneration
      after injury. Here, we review the information available on the structure and
      evolution of OMgp, summarize its tissue expression and discuss its putative
      role(s) during the development and in adult CNS.

PMID- 15145624
TI  - Political neglect in India's health.

PMID- 15145623
TI  - Neuroprotection and peptide toxins.
AB  - Neurodegeneration induced by excitatory neurotransmitter glutamate is considered
      to be of particular relevance in several types of acute and chronic neurological
      impairments ranging from cerebral ischaemia to neuropathological conditions such
      as motor neuron disease, Alzheimer's, Parkinson's disease and epilepsy. The
      hyperexcitation of glutamate receptors coupled with calcium overload can be
      prevented or modulated by using well-established competitive and non-competitive
      antagonists targeting ion/receptor channels. The exponentially increasing body of
      pharmacological evidence over the years indicates potential applications of
      peptide toxins, due to their exquisite subtype selectivity on ion channels and
      receptors, as lead structures for the development of drugs for the treatment of
      wide variety of neurological disorders. This review comprehensively highlights
      the overview of the diversity in the molecular as well as neurobiological
      mechanisms of different peptide toxins derived from venomous animals with
      particular reference to neuroprotection. In addition, the potential applications
      of peptide toxins in the diagnosis and treatment of neurological disorders such
      as neuromuscular disorders, epilepsy, Alzheimer's and Parkinson's diseases,
      gliomas and ischaemic stroke and their future prospects in the diagnosis as well
      as in the therapy are addressed.

PMID- 15145625
TI  - Dangerous pathogens in the laboratory: from smallpox to today's SARS setbacks and
      tomorrow's polio-free world.

PMID- 15145626
TI  - How to prevent cannabis-induced psychological distress...in politicians.

PMID- 15145627
TI  - Psychological, physiological, and drug interventions for type 2 diabetes.

PMID- 15145628
TI  - Statins for the treatment of multiple sclerosis: cautious hope.

PMID- 15145629
TI  - Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up
      of a prospective randomised study.
AB  - BACKGROUND: Breastfeeding is associated with reduced cholesterol concentration
      later in life, but previous studies have not used random assignment of infant
      diet with prospective follow-up. We tested the hypothesis that breastmilk feeding
      benefits the lipoprotein profile in adolescents born preterm, in whom
      randomisation to different diets at birth is feasible. METHODS: 926 infants born
      preterm were randomly assigned in two parallel trials to receive (trial 1)
      donated banked breastmilk or preterm formula, or (trial 2) standard term formula
      or preterm formula, as sole diet or as supplements to mother's milk in both
      trials. We followed up 216 participants at age 13-16 years and measured ratio of
      low-density to high-density lipoprotein cholesterol (LDL to HDL), ratio of
      apolipoprotein B to apolipoprotein A-1 (apoB to apoA-1), and concentration of C
      reactive protein (CRP; a measure of the inflammatory process associated with
      atherosclerosis). RESULTS: Adolescents who had been randomised to banked
      breastmilk had a lower CRP concentration (p=0.006) and LDL to HDL ratio (mean
      difference 0.34 [14% lower], 95% CI -0.67 to -0.01; p=0.04) than those given
      preterm formula. A greater proportion of human milk intake in infancy was
      associated with lower ratios of LDL to HDL (p=0.03) and apoB to apoA-1 (p=0.004)-
      independent of gestation and potential confounding factors--and with lower CRP
      concentration (p=0.03). CRP concentration correlated with the two lipoprotein
      ratios (p<0.0001 and p=0.003, respectively). INTERPRETATION: Our data provide
      experimental evidence for the long-term benefits of breastmilk feeding on the
      risk of atherosclerosis.

PMID- 15145630
TI  - Cystic bronchiectasis.

PMID- 15145631
TI  - Psychological and social sequelae of cannabis and other illicit drug use by young
      people: a systematic review of longitudinal, general population studies.
AB  - BACKGROUND: Use of illicit drugs, particularly cannabis, by young people is
      widespread and is associated with several types of psychological and social harm.
      These relations might not be causal. Causal relations would suggest that
      recreational drug use is a substantial public health problem. Non-causal
      relations would suggest that harm-reduction policy based on prevention of drug
      use is unlikely to produce improvements in public health. Cross-sectional
      evidence cannot clarify questions of causality; longitudinal or interventional
      evidence is needed. Past reviews have generally been non-systematic, have often
      included cross-sectional data, and have underappreciated the extent of
      methodological problems associated with interpretation. METHODS: We did a
      systematic review of general population longitudinal studies reporting
      associations between illicit drug use by young people and psychosocial harm.
      FINDINGS: We identified 48 relevant studies, of which 16 were of higher quality
      and provided the most robust evidence. Fairly consistent associations were noted
      between cannabis use and both lower educational attainment and increased reported
      use of other illicit drugs. Less consistent associations were noted between
      cannabis use and both psychological health problems and problematic behaviour.
      All these associations seemed to be explicable in terms of non-causal mechanisms.
      INTERPRETATION: Available evidence does not strongly support an important causal
      relation between cannabis use by young people and psychosocial harm, but cannot
      exclude the possibility that such a relation exists. The lack of evidence of
      robust causal relations prevents the attribution of public health detriments to
      illicit drug use. In view of the extent of illicit drug use, better evidence is
      needed.

PMID- 15145632
TI  - Systematic review and meta-analysis of randomised controlled trials of
      psychological interventions to improve glycaemic control in patients with type 2
      diabetes.
AB  - BACKGROUND: Adherence difficulties and psychological problems are associated with
      poor glycaemic control in diabetes. We undertook a systematic review and meta
      analysis of psychological therapies to assess their effectiveness in improving
      glycaemic control in type 2 diabetes. METHODS: We searched MEDLINE, PsychINFO,
      EMBASE, and the Cochrane Central Register of Controlled Trials up to January,
      2003. Eligible studies were randomised controlled trials that involved people
      with type 2 diabetes and evaluated a psychological therapy (counselling,
      cognitive behaviour therapy, or psychodynamic therapy) to improve diabetes
      control. We extracted the number of participants, their age, duration of
      diabetes, glycaemic control, type of psychological therapy, its mode of delivery,
      and type of intervention in the control group. The main outcome was long-term
      glycaemic control measured by percentage of glycated haemoglobin. Blood glucose
      concentration, weight, and psychological distress were also measured. Pooled
      standardised effect sizes were calculated. FINDINGS: 25 trials were eligible for
      the review. In 12 trials, the mean percentage glycated haemoglobin was lower in
      people assigned a psychological intervention than in the control group (usual
      care, education, waiting list, or attention control); the pooled mean difference
      was -0.32 (95% CI -0.57 to -0.07) equivalent to an absolute difference of -0.76%.
      There were non-significant differences in blood glucose concentration (eight
      trials; -0.11 [-0.65 to 0.42]) and weight gain (nine trials; 0.37 [-0.18 to
      0.93]). Psychological distress was significantly lower in the intervention groups
      (five trials; -0.58 [-0.95 to -0.20]). INTERPRETATION: In type 2 diabetes, there
      are improvements in long-term glycaemic control and psychological distress but
      not in weight control or blood glucose concentration in people who receive
      psychological therapies.

PMID- 15145633
TI  - Efficacy of rectal artesunate compared with parenteral quinine in initial
      treatment of moderately severe malaria in African children and adults: a
      randomised study.
AB  - BACKGROUND: Many patients with malaria of increasing severity cannot take
      medicines orally, and delay in injectable treatment can be fatal. We aimed to
      assess the reliability of absorption, antimalarial efficacy, and tolerability of
      a single rectal dose of artesunate in the initial management of moderately severe
      falciparum malaria. METHODS: 109 children and 35 adults were randomly assigned to
      rectal artesunate (single dose of about 10 mg/kg) or parenteral quinine treatment
      (10 mg/kg at 0, 4, and 12 h). The primary endpoint was the proportion of patients
      with peripheral asexual parasitaemia of less than 60% of that at baseline after
      12 h. Secondary endpoints were clinical response and concentrations of drug in
      plasma. Analysis was by intention-to-treat. FINDINGS: All artesunate-treated
      patients had pharmacodynamic or pharmacokinetic evidence of adequate drug
      absorption. 80 (92%) of 87 artesunate-treated children had a 12 h parasite
      density lower than 60% of baseline, compared with three of 22 (14%) receiving
      quinine (relative risk 0.09 [95% CI 0.04-0.19]; p<0.0001). In adults,
      parasitaemia at 12 h was lower than 60% of baseline in 26 (96%) of 27 receiving
      artesunate, compared with three (38%) of eight receiving quinine (relative risk
      0.06 [0.01-0.44]; p=0.0009). These differences were greater at 24 h. Clinical
      response was equivalent with rectal artesunate and parenteral quinine.
      INTERPRETATION: A single rectal dose of artesunate is associated with rapid
      reduction in parasite density in adults and children with moderately severe
      malaria, within the initial 24 h of treatment. This option is useful for
      initiation of treatment in patients unable to take oral medication, particularly
      where parenteral treatment is unavailable.

PMID- 15145634
TI  - Progressive binasal hemianopia.

PMID- 15145635
TI  - Oral simvastatin treatment in relapsing-remitting multiple sclerosis.
AB  - Many drugs have been approved for relapsing forms of multiple sclerosis but are
      only partly effective, are injected, and are expensive. We aimed to investigate
      use of of oral simvastatin (80 mg) in 30 individuals with relapsing-remitting
      multiple sclerosis. The mean number of gadolinium-enhancing lesions at months 4,
      5, and 6 of treatment was compared with the mean number of lesions noted on
      pretreatment brain MRI scans. Number and volume of Gd-enhancing lesions declined
      by 44%, (p<0.0001) and 41% (p=0.0018), respectively. Treatment was well
      tolerated. Oral simvastatin might inhibit inflammatory components of multiple
      sclerosis that lead to neurological disability.

PMID- 15145636
TI  - Serum lipopolysaccharide-binding protein prediction of severe bacterial infection
      in cirrhotic patients with ascites.
AB  - Serum lipopolysaccharide-binding protein is increased in a subset of non-infected
      ascitic cirrhotic patients, a finding previously related to bacterial passage
      from the gut to the circulation without overt infection. We prospectively
      analysed the risk factors associated with a first episode of severe bacterial
      infection in 84 ascitic cirrhotics, followed up for a median of 46 weeks. The
      cumulative probability of such infection in patients with raised and normal
      lipopolysaccharide-binding protein was 32.4% and 8.0% (p=0.004), respectively.
      Increased lipopolysaccharide-binding protein was the only factor independently
      associated with severe bacterial infection in a multivariate analysis (relative
      risk 4.49, 95% CI 1.42-14.1). Monitoring of serum lipopolysaccharide-binding
      protein could, therefore, help to target cirrhotic patients with ascites for
      antibiotic prophylaxis.

PMID- 15145637
TI  - Cerebral palsy.
AB  - Cerebral palsy, a range of non-progressive syndromes of posture and motor
      impairment, is a common cause of disability in childhood. The disorder results
      from various insults to different areas within the developing nervous system,
      which partly explains the variability of clinical findings. Management options
      include physiotherapy, occupational and speech therapy, orthotics, device
      assisted modalities, pharmacological intervention, and orthopaedic and
      neurosurgical procedures. Since 1980, modification of spasticity by means of
      orally administered drugs, intramuscular chemodenervation agents (alcohol,
      phenol, botulinum toxin A), intrathecally administered drugs (baclofen), and
      surgery (neurectomy, rhizotomy) has become more frequent. Family-directed use of
      holistic approaches for their children with cerebral palsy includes the
      widespread adoption of complementary and alternative therapies; however, the
      prevalence of their use and the cost of these options are unknown. Traditional
      medical techniques (physiotherapy, bracing, and orthopaedic musculoskeletal
      surgery) remain the mainstay of treatment strategies at this time. This seminar
      addresses only the musculoskeletal issues associated with cerebral palsy and only
      indirectly discusses the cognitive, medical, and social issues associated with
      this diagnosis.

PMID- 15145638
TI  - Yes, survive I did...

PMID- 15145639
TI  - Preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) was introduced at the beginning of the
      1990s as an alternative to prenatal diagnosis, to prevent termination of
      pregnancy in couples with a high risk for offspring affected by a sex-linked
      genetic disease. At that time, embryos obtained in vitro were tested to ascertain
      their sex, and only female embryos were transferred. Since then, techniques for
      genetic analysis at the single-cell level, involving assessment of first and
      second polar bodies from oocytes or blastomeres from cleavage-stage embryos, have
      evolved. Fluorescence in-situ hybridisation (FISH) has been introduced for the
      analysis of chromosomes and PCR for the analysis of genes in cases of monogenic
      diseases. In-vitro culture of embryos has also improved through the use of
      sequential media. Here, we provide an overview of indications for, and techniques
      used in, PGD, and discuss results obtained with the technique and outcomes of
      pregnancies. A brief review of new technologies is also included.

PMID- 15145640
TI  - Early origins of cardiovascular disease: is there a unifying hypothesis?

PMID- 15145642
TI  - Post-traumatic stress in former Ugandan child soldiers.

PMID- 15145643
TI  - Post-traumatic stress in former Ugandan child soldiers.

PMID- 15145644
TI  - Post-traumatic stress in former Ugandan child soldiers.

PMID- 15145645
TI  - Post-traumatic stress in former Ugandan child soldiers.

PMID- 15145646
TI  - Unsafe injections and transmission of HIV-1 in sub-Saharan Africa.

PMID- 15145648
TI  - Unsafe injections and transmission of HIV-1 in sub-Saharan Africa.

PMID- 15145649
TI  - Unsafe injections and transmission of HIV-1 in sub-Saharan Africa.

PMID- 15145650
TI  - European Clinical Trials Directive: the Italian position.

PMID- 15145651
TI  - Rising dengue death toll in Indonesia.

PMID- 15145652
TI  - Patients' charges in Slovakia.

PMID- 15145653
TI  - A need to rethink social psychiatry in Europe.

PMID- 15145654
TI  - More than I wanted to know.

PMID- 15145655
TI  - Evidence.

PMID- 15145656
TI  - Meeting fatigue.

PMID- 15145658
TI  - Current concepts in the embryology and genetics of cleft lip and cleft palate.
AB  - Many mechanisms underlying normal and abnormal craniofacial embryogenesis are
      well understood. The genetic factors that provoke abnormal development and result
      in orofacial clefts are not clear, but much progress has occurred in our
      understanding. Genes or chromosomal rearrangements on many chromosomes can lead
      to syndromes that include orofacial clefts. This diversity in the mechanisms that
      can lead to syndromic clefts highlights the fact that the processes leading to
      the development of the oral cavity and face are complex and sensitive to
      disturbances at multiple timepoints or within multiple genetic domains. As for
      nonsyndromic clefting, large-scale family studies are consistent with one or a
      few loci exerting major effects on phenotypic expression, although no single gene
      has been identified as a "necessary" locus for development of nonsyndromic
      clefts. Rather, the emerging consensus is that the genetic etiology of
      nonsyndromic clefting is complex, with several loci showing significant results
      in at least some studies. Some of these loci may be genes for susceptibility to
      environmental factors, some may be modifying loci, and some may be "necessary"
      loci. Mutations in genes that are now known to control early development are
      logical candidate genes for future studies of nonsyndromic orofacial clefting.
      Continued genetic analyses and developmental studies are crucial for eventual
      understanding of the complex etiology of these common congenital anomalies.

PMID- 15145659
TI  - Three-dimensional technology for documentation and record keeping for patients
      with facial clefts.
AB  - The surface laser scanner has great potential as a method for documentation of
      cleft infant due to its accuracy, ease of use, and convenience. The image scan be
      stored in the computer for easy access. As purchasing costs decrease, its
      acquisition will be facilitated, resulting in an increase in its use.

PMID- 15145660
TI  - Nasoalveolar molding for infants born with clefts of the lip, alveolus, and
      palate.
AB  - The principle objective of presurgical nasoalveolar molding (NAM) is to reduce
      the severity of the initial cleft deformity. This enables the surgeon and the
      patient to enjoy the benefits associated with a repair of a cleft deformity that
      is of minimal severity. Retraction of the premaxilla, presurgical elongation of
      the columella, correction of the nasal cartilage deformity, alignment of the
      cleft alveolar segments, increase in the surface area of the nasal mucosal
      lining, up-righting of the columella, and achieving close approximation of the
      cleft lip segments at rest result from gentle application of forces through the
      NAM appliance. Preservation of these presurgical changes is achieved through the
      coordinated and modified surgical technique of the primary cleft repair.

PMID- 15145662
TI  - Unilateral cleft lip-nose repair--long-term outcome.
AB  - Good to excellent results have consistently been achieved by the authors in
      primary unilateral cleft lip-nose repair. Modifications and improvements in their
      original technique have led to better symmetry and balance, with less scarring.
      This technique, when performed by experienced surgeons, yields consistent,
      predictable, and achievable outcomes for all patients with unilateral cleft lip
      and nose, where normal appearance and function at conversational distance is the
      standard of care. The achievement of excellence in soft tissue and skeletal
      restoration optimizing each patient's growth potential depends on a surgical
      orthodontic-speech-oriented treatment plan. Long-term outcomes demonstrating
      consistently good to excellent results can be achieved using this primary
      technique if it is backed up with a dedicated, multidisciplinary ongoing
      treatment protocol.

PMID- 15145661
TI  - Functional matrix cleft repair: principles and techniques.
AB  - As an application of developmental anatomy, functional matrix cleft repair has
      scientific value. It tests out many aspects of periosteal physiology, and it is
      based squarely on concepts central to orthodontics. The "molecular revolution"
      has melded together developmental anatomy and genetics to create a new and
      clinically relevant model of facial development. This article outlines the
      scientific rationale for cleft repair based on this model.

PMID- 15145663
TI  - Bilateral cleft lip.
AB  - The surgeon's objectives are normal nasolabial appearance and normal speech. The
      principles for synchronous repair of bilateral cleft lip have been established,
      and the techniques continue to evolve. Primary repair impairs maxillary growth,
      but little can be done at this time except to practice gentle craftsmanship and
      to minimize tension on the lower labial closure. The cutaneous lip should never
      be reopened for revision, and the number of secondary procedures involving the
      nasal cartilages should be kept to a minimum. Many adolescents with repaired
      bilateral cleft lip need maxillary advancement to improve projection of the nasal
      tip, to protrude the upper lip, and to attain normal sagittal skeletal harmony.
      With expected improvements in the technology of distraction osteogenesis,
      maxillary advancement may someday become as acceptable as orthodontic treatment.

PMID- 15145664
TI  - Distraction osteogenesis in Pierre Robin neonates with airway obstruction.
AB  - Mandibular distraction osteogenesis can be a safe and effective way to avoid
      tracheostomy placement in selected neonates with Pierre Robin sequence,with or
      without other associated syndromes. In non-syndromic Pierre Robin sequence
      syndromes, this procedure, in the current author's experience, has provided
      definitive correction of both airway obstruction and micrognathia. The cost to
      patients and families appropriately treated by mandibular distraction
      osteogenesis is substantially less than tracheostomy. Mandibular distraction does
      not involve the ongoing maintenance, medical care, and high risk of mortality
      associated with tracheostomy. A support team of pediatric anesthesia, pulmonary,
      and otolaryngology specialists is required for the safe and successful selection
      and treatment of this group of patients with Pierre Robin sequence using
      mandibular distraction. The author's investigation of this group is ongoing.

PMID- 15145665
TI  - Cleft palate repair: art and issues.
AB  - Caring for the child with cleft palate requires a multidisciplinary approach that
      begins with evaluation for other possible congenital anomalies, decisions about
      timing of repair, and choice of techniques. Postoperative follow-up similarly
      requires a team approach and should include an otolaryngologist, an orthodontist,
      and a speech therapist. The art of cleft palate repair has enjoyed a decade rich
      in new developments. New techniques have been developed, and standard techniques
      have been refined. Most importantly, the need for prospective, randomized trials
      to objectively compare surgical techniques has been recognized. Initiation and
      completion of these trials will improve outcomes for patients with cleft palate
      repairs.

PMID- 15145667
TI  - Evaluation of cleft palate speech.
AB  - Children born with palatal clefts are at risk for speech/language delay and
      speech problems related to palatal insufficiency. These individuals require
      regular speech evaluations, starting in the first year of life and often
      continuing into adulthood. The primary role of the speech pathologist on the
      cleft palate/craniofacial team is to evaluate whether deviations in oral cavity
      structures, such as the velopharynx, negatively impact speech production. This
      article focuses on the assessment of velopharyngeal function before and after
      palatal surgery.

PMID- 15145666
TI  - The Children's Hospital of Philadelphia modification of the Furlow double
      opposing z-palatoplasty: long-term speech and growth results.
AB  - Of the 261 nonsyndromic patients we studied, over 90% had minimal or absent
      hypernasality, almost 86% had inconsistent or no nasal emission, and 95% had no
      articulation errors related to velar function. The patients with a Pittsburgh
      score indicating an incompetent velopharyngeal mechanism comprised only about 6%
      of the group. Ninety-four percent had a socially functional speech quality.
      Secondary surgery was done in 6.5% of patients and was done or was recommended in
      about 8% of patients. Patients with isolated cleft palate seemed to do less well,
      although their outcomes were not statistically different from those with complete
      unilateral and bilateral clefts. Relaxing incisions have kept our fistula rate to
      an acceptably low rate of 6.8%. No major soft palate dehiscences or hard palate
      flap losses have occurred. The speech outcomes we are achieving are improved over
      our historical results and compared with published reports using nondouble
      reversing z-palatoplasty techniques. Similar outcomes with the Furlow repair have
      been confirmed. Maxillary growth, occlusion, and the need for orthognathic
      surgery do not seem to be influenced by the CHOP modification of the Furlow
      double-opposing z-palatoplasty. These modifications facilitate a tension free
      closure and a low fistula rate.

PMID- 15145668
TI  - The evaluation and management of velopharyngeal dysfunction.
AB  - Several interventions are available for management of VPD. Using an approach of
      differential management based on differential diagnosis, VPD can be effectively
      treated in most patients. The current challenge for the VPD care team, however,
      is to resolve the signs and symptoms of VPD without exchanging them for a
      different but an equally or more morbid set of signs and symptoms.

PMID- 15145669
TI  - Orthodontic treatment for patients with clefts.
AB  - Orthodontic strategies continue to evolve as new methods and treatment concepts
      more directly address the specific problems of patients who have clefts. By
      continual review of treatment outcomes and comparing outcomes with patients'
      problem lists and treatment objectives, clinicians will identify areas of
      treatment needing improvement and formulate hypotheses for future research.

PMID- 15145670
TI  - Distraction osteogenesis for the cleft lip and palate patient.
AB  - Gradual maxillary distraction by modified osteotomies and external force systems
      is a procedure with minimal morbidity and few complications. The interaction
      between surgeons and orthodontists is critical, however. The wide range of
      possibilities for remodeling a hypoplastic maxilla by distraction allows the
      potential to simultaneously advance and to elongate the midface, thereby
      restructuring the skeletal framework with mature new bone. An expansion of all
      the soft tissues of the face and palate (muscles, nerves, vessels, mucosa, skin)
      occurs in conjunction with bone elongation. This process ultimately produces
      excellent functional and aesthetic results in patients with midface deficiency,
      thus restoring their facial appearance and avoiding many years of facial
      deformity and associated psychologic sequelae.

PMID- 15145671
TI  - Management of alveolar clefts.
AB  - Treatment philosophies in the management of alveolar clefts have changed greatly
      over the years. Currently. the most widely accepted protocol is for repair using
      autologous cancellous bone from the iliac crest during the stage of mixed
      dentition. Preliminary data suggest that the appropriate age for surgical repair
      during the secondary phase can be decreased without evidence of limitation of
      facial growth. Further long-term studies are necessary to support this protocol,
      however. With a multidisciplinary approach between the various medical and dental
      specialties, it is now commonplace to achieve normal dentofacial aesthetics and
      function. The continued advances in medical and dental technology have further
      contributed to the excellent outcomes that are now achieved.

PMID- 15145672
TI  - Cleft-orthognathic surgery.
AB  - For the cleft patient presenting in adolescence with a jaw discrepancy and
      malocclusion, misinformation and limited available surgical and dental expertise
      often prevents a favorable facial reconstruction and dental rehabilitation. A
      major advantage of the modified Le Fort I osteotomy is its ability to
      simultaneously close cleft dental gap(s), resolve oronasal fistulas, manage
      skeletal defects, stabilize dentoalveolar segments, and correct jaw deformities.
      When a thoughtful staging of reconstruction is undertaken, individuals born with
      cleft lip and palate can reach adolescence after undergoing only a limited number
      of operations and interventions, without negative attention being drawn to their
      original malformation.

PMID- 15145673
TI  - Residual deformities after repair of clefts of the lip and palate.
AB  - Every effort should be made to achieve the best possible results at the time of
      lip and palate repair. Appropriate and extensive evaluation, short- and long-term
      planning with optimal timing for each procedure, close cooperation with the
      members of the craniofacial team, selection of the most appropriate technique(s),
      careful execution, and close follow-up are prerequisites for success. Additional
      surgical procedures or revisions are required to improve appearance and function
      and to manage unfavorable results of previous interventions. Such procedures
      should be also planned carefully, taking into consideration all aspects of the
      deformity to provide our patients with superior habilitation.

PMID- 15145674
TI  - Psychological issues in cleft lip and palate.
AB  - The treatment of cleft lip and palate extends over the infancy, childhood, and
      adolescence of individuals who are born with this condition. The children and
      their families contend with multiple surgeries throughout these years. Depending
      on the severity of the cleft, the families may also need to cope with speech
      therapy, ear infections, learning disabilities,and various orthodontic
      treatments. The end result of these treatments and interventions should be a
      child, teen, or adult who is an appropriately contributing member of society at
      each stage of development. The psychological support needed to enable a child to
      meet that goal should be provided by family, school, the surgeon, and other
      members of the cleft treatment team. These adults should demonstrate a belief in
      the child's ability to cope with the challenges of cleft lip and palate treatment
      and should focus the child on the efficacy he will gain from having had the
      experience of growing up with a cleft lip and palate.

PMID- 15145675
TI  - Prosthetic habilitation of patients with clefts.
AB  - Through clinical experience and research, treatment of cleft lip and palate has
      changed and im-proved dramatically. The team concept remains the key to success
      in the care of these patients. Prosthodontists remain integral members of this
      team because of the wide range of patient care services that they provide.

PMID- 15145676
TI  - Facial growth of adults with unoperated clefts.
AB  - Studies of adult patients with unoperated complete unilateral cleft lip and
      palate indicate that there is normal potential for maxillary growth. The maxilla
      in the unoperated patient is normally positioned or protruded. The protrusion of
      maxilla in the unoperated adult cleft patient is limited to the non-cleft side,
      contributing to hemifacial maxillary prognathism. Surgical scar tissue is known
      to interfere with the growth of the midface. Palatal surgery has more significant
      influence on the growth of the mid-face than the lip surgery; therefore, it is
      important to reduce the effect of surgery by delaying the timing of palatal
      surgery or changing the location of the surgical scar from the sutural areas.
      Delaying palatal surgery until the maxillary growth is complete is desirable but
      could lead to poor speech development. Therefore, it is essential to perform the
      palatal surgery before speech development. The other variables that affect the
      midface are the development genetic make-up of the cleft child, the amount of
      tissue deficiency, timing of surgery, surgical technique, and the skill of the
      surgeon. Surgeries continue to have some inhibitory effect on maxillary growth,
      but it is essential to recognize and perform those surgical procedures that have
      the least effect on growth of the maxilla. This will help minimize extensive
      orthodontic treatment and eliminate major secondary orthognathic surgery for
      correction of the abnormal growth of the maxilla.

PMID- 15145678
TI  - Feature synergy depends on feature contrast and objecthood.
AB  - Pairs of texture figures, defined by contrast in spatial frequency, orientation
      or both cues (redundant texture definition) had to be detected within a
      homogeneous Gabor field. In line with expectation we find better detection
      performance for arrangements with higher feature contrast along the border where
      the figures abut. Redundantly defined figures show synergy, a significant
      performance increase compared to the prediction of independent processing of
      orientation and spatial frequency cues. As found in previous studies [Spatial
      Vision 16 (2003) 459; Vision Research (submitted for publication)] this
      performance advantage is negatively correlated with visibility. In particular,
      figures with high border feature contrast are easily detectable but show weak
      synergy whereas figures with low border feature contrast are barely detectable
      but remarkably benefit from redundant texture definition. Closer analysis reveals
      that the form of the figures is also crucial: As long as they maintain a clear
      two dimensional shape the synergy effect is only marginally affected by variation
      figure size and border length. But when they degrade to one dimensional Gabor
      element arrays, synergy almost completely vanishes. The results imply that both
      factors, low visibility and objecthood, are critical for feature synergy. We
      conclude that facilitation across feature domains serves to segregate figure from
      ground when the signal from a single domain is too weak to enable object
      detection and vanishes under conditions of stable object vision.

PMID- 15145679
TI  - Illusory contours and surfaces without amodal completion and depth
      stratification.
AB  - Cognitive and figural cues were studied in modified Ehrenstein figures made from
      letters of the alphabet instead of radial lines. Capital letters with and without
      terminators (L, J vs O, D) were used, oriented towards or away from the central
      gap. Three groups, of 14 subjects each, estimated the magnitude of either (i) the
      illusory contour, (ii) brightness enhancement, or (iii) apparent depth. Strong
      illusory contour formation and brightness enhancement, but no depth
      stratification, were perceived in figures devoid of apparent occlusion and amodal
      completion. These results demonstrate that the Ehrenstein illusion can arise from
      line ends--with no need for perceptual completion, showing that illusory
      boundaries and surfaces can be dissociated from apparent depth. Results support a
      bottom-up explanation in terms of end-stopped neurons in the visual cortex.
      Conversely, top-down processes appear to be responsible for depth stratification.

PMID- 15145680
TI  - A paraxial schematic eye model for the growing C57BL/6 mouse.
AB  - PURPOSE: The mouse eye has potential to become an important model for studies on
      the genetic control of eye growth and myopia. However, no data are published on
      the development of its optical properties. We developed a paraxial schematic
      model of the growing eye for the most common laboratory mouse strain, the C57BL/6
      mouse, for the age range between 22 and 100 days. METHODS: Refractive development
      was followed with eccentric infrared photorefraction and corneal curvature with
      infrared photokeratometry. To measure ocular dimensions, freshly excised eyes
      were immediately frozen after enucleation to minimize distortions. Eyes were cut
      with a cryostat down to the bisecting horizontal plane, until the optic nerve
      head became visible. The standard deviations were +/-10 microm for repeated
      measurements in highly magnified videographs, taken in several section planes
      close to the equator in the same eyes. To evaluate inter-eye and inter-individual
      variability, a total of 20 mice (34 eyes) were studied, with 3-4 eyes for each of
      the 9 sampling ages. Schematic eye models were developed using paraxial ray
      tracing software (OSLO, LT Lambda Research Corporation, and a self-written
      program). RESULTS: The measured refractive errors were initially +4.0+/-0.6 D at
      approximately 30 days, and levelled off with +7.0+/-2.5 D at about 70 days.
      Corneal radius of curvature did not change with age (1.414+/-0.019 mm). Both
      axial lens diameter and axial eye length grew linearly (regression equations:
      lens, 1619 microm +5.5 microm/day, R=0.916; axial length, 2899 microm +4.4
      microm/day, R=0.936). The lens grew so fast that vitreous chamber depth declined
      with age (regression equation: 896 microm -3.2 microm/day, R=0.685). The radii of
      curvature of the anterior lens surface increased during development (from 0.982
      mm at day 22 to 1.208 mm at day 100), whereas the radii of the posterior lens
      surface remained constant (-1.081+/-0.054 mm). The calculated homogeneous lens
      index increased linearly with age (from 1.568 to 1.605). The small eye artifact,
      calculated from the dioptric difference of the positions of the vitreo-retinal
      interface and the photoreceptor plane, increased from +35.2 to +39.1 D, which was
      much higher than the hyperopia measured with photorefraction. Retinal image
      magnification increased from 31 to 34 microm/deg, and the f/number remained < or
      =1 at all ages, suggesting a bright retinal image. A calculated axial eye
      elongation of 5.4-6.5 microm was sufficient to make the schematic eye 1 D more
      myopic. CONCLUSIONS: The most striking features of the mouse eye were that linear
      growth was slow but extended far beyond sexual maturity, that the corneal
      curvature did not increase, and that the prominent lens growth caused a
      developmental decline of the vitreous chamber depth.

PMID- 15145681
TI  - Effect of positive and negative defocus on contrast sensitivity in myopes and non
      myopes.
AB  - This study investigated the effect of lens induced defocus on the contrast
      sensitivity function in myopes and non-myopes. Contrast sensitivity for up to 20
      spatial frequencies ranging from 1 to 20 c/deg was measured with vertical sine
      wave gratings under cycloplegia at different levels of positive and negative
      defocus in myopes and non-myopes. In non-myopes the reduction in contrast
      sensitivity increased in a systematic fashion as the amount of defocus increased.
      This reduction was similar for positive and negative lenses of the same power (p
      = 0.474). Myopes showed a contrast sensitivity loss that was significantly
      greater with positive defocus compared to negative defocus (p = 0.001). The
      magnitude of the contrast sensitivity loss was also dependent on the spatial
      frequency tested for both positive and negative defocus. There was significantly
      greater contrast sensitivity loss in non-myopes than in myopes at low-medium
      spatial frequencies (1-8 c/deg) with negative defocus. Latent accommodation was
      ruled out as a contributor to this difference in myopes and non-myopes. In
      another experiment, ocular aberrations were measured under cycloplegia using a
      Shack-Hartmann aberrometer. Modulation transfer functions were calculated using
      the second order term for defocus as well as the fourth order Zernike term for
      spherical aberration. The theoretical maximal contrast sensitivity based on
      aberration data predicted the measured asymmetry in contrast sensitivity to
      positive and negative defocus that was observed in myopic subjects. The observed
      asymmetry in contrast sensitivity with positive and negative defocus in myopes
      may be linked to the altered accommodative response observed in this group.

PMID- 15145682
TI  - Path perception during rotation: influence of instructions, depth range, and dot
      density.
AB  - How do observers perceive their direction of self-motion when traveling on a
      straight path while their eyes are rotating? Our previous findings suggest that
      information from retinal flow and extra-retinal information about eye movements
      are each sufficient to solve this problem for both perception and active control
      of self-motion [Vision Res. 40 (2000) 3873; Psych. Sci. 13 (2002) 485]. In this
      paper, using displays depicting translation with simulated eye rotation, we
      investigated how task variables such as instructions, depth range, and dot
      density influenced the visual system's reliance on retinal vs. extra-retinal
      information for path perception during rotation. We found that path errors were
      small when observers expected to travel on a straight path or with neutral
      instructions, but errors increased markedly when observers expected to travel on
      a curved path. Increasing depth range or dot density did not improve path
      judgments. We conclude that the expectation of the shape of an upcoming path can
      influence the interpretation of the ambiguous retinal flow. A large depth range
      and dense motion parallax are not essential for accurate path perception during
      rotation, but reference objects and a large field of view appear to improve path
      judgments.

PMID- 15145683
TI  - A new look at the Bezold-Brucke hue shift in the peripheral retina.
AB  - Experiments were conducted with a bipartite field to better understand the Bezold
      Brucke hue shift in the peripheral retina. The first experiment measured hue
      shift in the fovea and at 1 degrees and 8 degrees along the horizontal meridian
      of the nasal retina for nominal test wavelengths of 430, 450, 490, 520 and 610
      nm. Peripheral measurements were obtained under two adaptation conditions: after
      30 min dark adaptation and following a rod-bleach. Results indicated that foveal
      hue shifts differed from those obtained after a rod-bleach. Data from the rod
      bleach and no-bleach conditions in the periphery were similar, indicating that
      rods could not account for the differences between the foveal data and the rod
      bleach peripheral data. Hue shifts obtained for the 520 nm test stimulus, and to
      a smaller extent other test wavelengths, at 8 degrees nasal retinal eccentricity
      revealed that the wavelength of the matching stimulus depended upon the lateral
      position of the matching and test fields, and this effect was greater in the no
      bleach condition than the rod-bleach condition. Several factors were investigated
      in experiments 2 and 3 to explain the results with the 520 nm test field. It
      appears that differential rod density under the two half fields and the
      compression of photoreceptors by the optic disk may partially, but not fully,
      account for the 520 nm effect.

PMID- 15145684
TI  - Sound-aided recovery from and persistence against visual filling-in.
AB  - Disappearance phenomena, in which salient visual stimuli do not register
      consciously, have been known to occur. Recovery from such phenomena typically
      occurs through change in some visual attribute, such as increase in luminance
      contrast or stimulus duration. Thus far, there have been no reports of cross
      modal modulation of disappearance phenomena. In particular, what effect a cross
      modal attentional cue has on sensory suppression is unknown. Here, we show that
      an adapted, flickered visual target that is synchronous with a brief sound
      appears more vivid than a similarly adapted, otherwise identical, visual target
      that is offset in time by more than 200 ms from the auditory cue. We argue that
      the brief auditory stimuli momentarily boost the concurrent signal of the adapted
      visual stimulus at a site downstream of the visual adaptation, thus causing the
      transient recovery from the visual adaptation. Repetitive visual cues cause
      significantly less recovery from visual adaptation than repetitive auditory cues,
      implying that there are functions a cross-modal cue can perform that a cue of the
      same modality cannot. Moreover repetitive auditory cues selectively prevent
      synchronous visual targets from undergoing visual adaptation. Ours is the first
      report of cross-modal modulation of a disappearance phenomenon.

PMID- 15145685
TI  - Separation of edge detection and brightness perception.
AB  - When a low spatial frequency noise mask is superimposed onto a luminance
      staircase, the perceived brightness pattern is dramatically altered although the
      edges remain visible. We measured contrast thresholds for the edges and for the
      illusory scalloping (Chevreul-illusion), as a function of noise center spatial
      frequency. The masking tuning functions overlapped, but peaked at different
      spatial frequencies and contrast levels. The results suggest that perceived
      brightness is triggered only by the low spatial frequency components of the edges
      -the high spatial frequency components are not able to produce a brightness
      pattern.

PMID- 15145686
TI  - Magnocellular involvement in flanked-letter identification relates to the
      allocation of attention.
AB  - To verify the hypothesis that the magnocellular system is important to flanked
      letter identification [Neuropsychologia 40 (2002) 1881] because it subserves
      attention allocation, we conducted three letter-naming experiments in which we
      manipulated magnocellular involvement (colour vs. luminance contrast) and prior
      information regarding target-letter location. Location information was provided
      through constant presentation at the same location (Experiment 1) or through
      auditory precueing (Experiments 2 and 3). In control conditions, either no
      (Experiments 1 and 3) or invalid (Experiment 2) location information was given.
      In line with the hypothesis, magnocellular input helped flanked-letter
      identification only when no prior location information was given.

PMID- 15145687
TI  - Contrast-reversing global-motion stimuli reveal local interactions between first-
      and second-order motion signals.
AB  - Motion perception appears to be mediated by, at least, two systems: a first-order
      and a second-order system. To investigate the degree of interaction between these
      systems, we used a contrast-reversing global-motion stimulus in which the signal
      dots reverse their contrast polarity as they move. In response to such a
      stimulus, fullwave-rectifying second-order units would signal motion in the
      displacement direction and first-order units would signal motion in the opposite
      direction (reverse-phi motion). If these signals were of equal strength, then any
      inhibitory interaction between them would lead to motion nulling. Such a
      situation would account for the failure to perceive coherent motion with such a
      stimulus in a previous study [Vis. Res. 34 (1994) 2849]. In order to test for
      this possibility we manipulated the stimulus in order to reduce the strength of
      the second-order response relative to the first-order response. This was achieved
      by: decreasing dot contrast; increasing stimulus eccentricity; and increasing dot
      speed. These manipulations resulted in an increase in the perception of (first
      order mediated) reverse-phi motion. We conclude that interaction between first-
      and second-order motion signals occur at the local-motion-pooling level.

PMID- 15145688
TI  - Effects of spatial arrangement of visual stimulus on inverted self-motion
      perception induced by the foreground motion: examination of OKN-suppression
      hypothesis.
AB  - Our previous study revealed that a slowly moving foreground, which is presented
      in front of a fast-moving orthogonal background, can induce self-motion
      perception in the same direction as its motion (inverted vection; Vis. Res. 40
      (2000) 2915). The present study shows that inverted vection becomes stronger in
      the conditions where the foreground stimulus is presented in the central area of
      observer's visual field and the observer's eyes converge on the same depth plane.
      These stimulus conditions are consistent with the one where the foreground can
      induce observer's optokinetic nystagmus more effectively, and therefore, the
      results of this study support our hypothesis in that mis-registered eye-movement
      information caused by the suppression of optokinetic nystagmus induced by the
      foreground motion is a critical factor in perceiving inverted vection.

PMID- 15145689
TI  - Binocular correlation does not improve coherence detection for fronto-parallel
      motion.
AB  - We studied the low-level interactions between motion coherence detection and
      binocular correlation detection. It is well-established that e.g. depth
      information from motion parallax and from binocular disparities is effectively
      integrated. The question we aimed to answer is whether such interactions also
      exist at the very first correlation level that both mechanisms might have in
      common. First we quantitatively compared motion coherence detection and binocular
      correlation detection using similar stimuli (random pixels arrays, RPAs) and the
      same noise masking paradigm (luminance signal to noise ratio, LSNR). This showed
      that human observers are much more sensitive to motion than to binocular
      correlation. Adding noise therefore has a much stronger effect on binocular
      correlation than on motion detection. Next we manipulated the shape of the
      stimulus aperture to equalize LSNR thresholds for motion and binocular
      correlation. Motion sensitivity could be progressively reduced by shortening the
      length of the motion path, while keeping the aperture area constant. Changing the
      shape of the aperture did not affect binocular correlation sensitivity. A
      'balanced' stimulus, one with equal strengths of motion and binocular correlation
      signals was then used to study the mutual interactions. In accordance with
      previous results, motion was found to greatly facilitate binocular correlation.
      Binocular correlation, however did not facilitate motion detection. We conclude
      that interactions are asymmetrical; fronto-parallel motion is primarily detected
      monocularly and this information can then be used to facilitate binocular
      correlation, but binocular correlation cannot improve motion sensitivity.

PMID- 15145690
TI  - Oral and portal venous tolerance in the interferon-gamma knockout (GKO) mouse.
AB  - BACKGROUND: The role of the proinflammatory cytokine interferon-gamma (IFN-gamma)
      in the development of oral or portal venous tolerance is poorly defined. By using
      knockout mice for IFN-gamma (GKO mice), we investigated the effect of both oral
      and portal venous administration of alloantigen on the systemic delayed type
      hypersensitivity (DTH) response to alloantigen rechallenge. MATERIALS AND
      METHODS: C57BL/6 (B6) control and GKO mice (also on a B6 background) were given
      either saline or BALB/c spleen cells (25 million) by oral gavage (PO) or by
      injection into the portal vein (PV) on day 0. The injection of 10 million BALB/c
      spleen cells subcutaneously into the dorsal flanks was performed after 7 days
      followed by footpad injection of 10 million BALB/c spleen cells on day 14.
      Specific footpad swelling was measured 24 h later using a micrometer. Splenocyte
      responsiveness was measured by in vitro mixed lymphocyte culture and cytotoxic T
      lymphocyte assay. Cytokine production of interleukin (IL)-2, IL-4, IL-10, and IFN
      gamma was measured by enzyme-linked immunosorbent assay. RESULTS: Although B6
      mice given PO or PV saline demonstrated a DTH response of 0.47 +/- 0.04 mm and
      0.49 +/- 0.05 mm, respectively, in GKO mice, a greater DTH response of 0.72 +/-
      0.08 mm and 0.75 +/- 0.05 mm was measured after either PO or PV saline (P < 0.05,
      P < 0.05, respectively). In vitro MLC and CTL confirmed the heightened DTH
      response to BALB/c observed in GKO versus B6. Despite this heightened response in
      control GKO mice, the DTH response was completely suppressed in both GKO and B6
      mice, after both PO and PV BALB/c feedings (P < 0.001, P < 0.001, respectively,
      in both GKO and B6 mice). The unchanged brisk response to third-party C3H/HeJ
      demonstrated antigenic specificity. CONCLUSIONS: Although DTH responsiveness to
      alloantigen is increased in the absence of IFN-gamma, both oral and portal venous
      alloantigen-specific tolerance can still be established in GKO mice similar to
      that in control B6 mice. The achievement of a tolerogenic immune response by both
      oral and portal venous routes indicates that lack of IFN-gamma does not preclude
      the induction of tolerance in this murine model.

PMID- 15145691
TI  - Preclinical students: who are surgeons?
AB  - BACKGROUND: The purpose of the present study was to determine how preclinical
      medical students formulate their career choice and to determine the origin of
      negative perceptions regarding surgery as a career. MATERIALS AND METHODS: A
      qualitative study was performed with second-year medical students voluntarily
      participating in focus group study. Students with and without an interest in
      surgery attended. Topics discussed included factors influencing career choice,
      priorities, perceptions, exposure, and interactions with surgeons. Three
      investigators conducted independent content analysis. RESULTS: Career choices for
      students interested in surgery originated primarily from premedical school
      experiences/interactions with surgeons. In contrast, students not interested in
      surgery made career choices during medical school and choices were shaped
      primarily by second-year preceptors. The main priority for students interested in
      surgery was personal happiness that was perceived as being significantly
      dependent upon career satisfaction. Students not interested in surgery tended to
      separate happiness derived from career versus family. Negative perceptions toward
      surgery were developed and reinforced by media, preceptors, and classmates. All
      students had minimal exposure to surgeons during preclinical years and generally
      agreed that increased involvement with surgeons would be beneficial, particularly
      through preclinical preceptorships. CONCLUSIONS: Career choices of preclinical
      students interested in surgery were made prior to entering medical school,
      suggesting that outreach programs to high schools and colleges may beneficial.
      Negative perceptions about surgery develop through a variety of sources,
      including fellow classmates, preceptors, and the media. Surgeons need to take
      responsibility for these perceptions.

PMID- 15145692
TI  - The mean and standard deviation: what does it all mean?

PMID- 15145693
TI  - Why do students choose careers in surgery?
AB  - BACKGROUND: Recent changes in medical education have emphasized primary care
      careers. This could have a negative impact on the number of applicants to
      surgical residencies. We hypothesized that experiences during the third year
      surgical clerkship are influential for students' subsequent residency choice.
      MATERIALS AND METHODS: Third year medical students who completed their surgical
      clerkship in the 2001-02 academic year were surveyed pre- and post-surgical
      clerkship. Responses were analyzed and correlated to the 2003 match results.
      RESULTS: The response rate of students surveyed was 98% (82 surveys/83 match
      results). Pre-clerkship, 6/82 students (7%) expressed an interest in surgery or
      surgical subspecialty careers. Post-clerkship, 34/84 students (40%) expressed an
      increased interest a surgical career; 13/84 (15%) expressed a decreased interest,
      and 37% of students expressed no change in career interest. Of those students
      expressing an increased interest in surgery, the clerkship experiences most noted
      to be influential were (1) number of cases participated/scrubbed (95%), (2)
      resident interaction (85%), (3) faculty interaction (80%), and (4) number of
      cases observed (65%). The number of hours spent on rotation (call, rounds) was
      the leading experience associated with a decreased interest in a surgical career.
      12/83 students surveyed (14%) ultimately matched into a surgical program (NRMP
      2003 match results). CONCLUSIONS: These data suggest that operative exposure and
      interaction with residents and faculty have a positive influence in students'
      choice of a surgical career. Although only 6% of students expressed an interest
      in surgery pre-clerkship, a 2-fold increase in this number was noted in choice of
      residency (14%). Work hours were the primary negative indicator for surgery
      residency. As medical curriculum is restructured and surgical exposure decreased,
      these data underscore the importance of quality exposure to both procedures and
      role models during the 3rd year surgical clerkship.

PMID- 15145694
TI  - Characterization of somatostatin receptor expression in human pancreatic cancer
      using real-time RT-PCR.
AB  - BACKGROUND: Somatostatin inhibits cell proliferation and may act as a tumor
      suppressor by interacting with five different somatostatin receptors (SSTRs). We
      hypothesized that SSTR expression is down-regulated in human pancreatic cancer.
      In the current study, we used a powerful real-time RT-PCR technique to examine
      the mRNA expression levels of all five SSTR subtypes in human pancreatic cancer.
      MATERIALS AND METHODS: Total RNA was extracted from three pancreatic cancer cell
      lines (Panc-1, MIA PaCa-2, and Hs 766T), three surgical specimens of pancreatic
      cancer, and adjacent pancreatic tissue, and a pancreatic cancer cell line
      transfected with the SSTR-2 gene. Specific primers were designed and mRNA levels
      for the five SSTRs were analyzed with real-time quantitative RT-PCR using a Bio
      Rad iCycler system. RESULTS: The pancreatic tumor specimens had a 2.5- and 4.3
      fold reduction of SSTR-2 and SSTR-5 mRNA levels, respectively, as compared to
      their adjacent normal pancreatic tissues. SSTR-1 and SSTR-3 were also detected in
      both the cancer specimens and the adjacent tissues, but SSTR-4 was absent. Human
      pancreatic cancer cell lines also expressed SSTR-2 and SSTR-5 mRNA, but not SSTR
      1, SSTR-3, and SSTR-4. Up-regulation of SSTR-2 mRNA by 2.2 x 10(4)-fold in Panc-1
      cells resulted in receptor expression and growth inhibition. CONCLUSION:
      Expression of SSTR-2 and SSTR-5 could be important in the growth inhibitory
      effect of somatostatin in human pancreatic cancer. Down-regulation of SSTR
      transcription or SSTR mRNA instability may result in loss of a tumor suppressive
      effect of SSTRs in human pancreatic cancer.

PMID- 15145695
TI  - COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer
      in vitro.
AB  - PURPOSE: The purpose of this work was to determine the in vitro effect of
      Rofecoxib and specific COX 1 and COX 2 inhibitors in regards to cell growth and
      apoptotic and necrotic activity. INTRODUCTION AND OBJECTIVE: Rofecoxib (Vioxx) is
      a nonsteroidal anti-inflammatory agent (NSAID) that selectively inhibits
      cyclooxygenase-2 (COX-2). The inducible isoform of COX-2 is overexpressed in many
      gastrointestinal and genitourinary tract tumors. We hypothesized that in vitro
      treatment with both COX-1 and COX-2 inhibitors would significantly reduce
      cellular proliferation of bladder cancer cells by apoptotic pathways. MATERIALS
      AND METHODS: Two human bladder cancer cell lines were grown in culture using
      standard techniques and treated with Rofecoxib at doses ranging from 125
      microg/well serially diluted down to 8.0 microg/well. Catechin (COX 1 inhibitor)
      and NS398 (COX 2 inhibitor) were used at doses of 50 and 100 microM. Cell
      viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated by the
      Annexin V FITC Assay. Statistical analysis was performed by ANOVA. RESULTS:
      Rofecoxib, Catechin, and NS398 all exhibited significant inhibition of cell
      growth when compared to the nontreated controls. Significant changes in apoptotic
      activity were observed in all agents tested in both the T24 and the TCCSUP cells.
      CONCLUSIONS: Selective COX-2 inhibition, using the well-tolerated and
      commercially available Rofecoxib (VIOXX) and specific COX 1 and 2 inhibitors,
      reduced the growth of human bladder cancer in vitro by apoptotic mechanisms.
      Further in vivo and human studies are warranted to evaluate the safety and
      clinical utility of this agent in patients with bladder cancer.

PMID- 15145696
TI  - Antiproliferative and apoptotic effects of rofecoxib on esophageal cancer in
      vitro(1).
AB  - BACKGROUND: The incidence of Barrett's adenocarcinoma has increased dramatically
      in the United States, whereas squamous cell carcinoma of the esophagus remains a
      worldwide problem. Cyclooxygenase (COX)-2 may play an important role in
      gastrointestinal carcinogenesis and is overexpressed in both Barrett's metaplasia
      and adenocarcinoma. We hypothesized that a selective and commercially available
      COX-2 inhibitor, rofecoxib (Vioxx), would inhibit growth of Barrett's
      adenocarcinoma and squamous cell carcinoma of the esophagus by apoptotic
      pathways. Additional comparison studies were performed with commercially
      available COX-2 and COX-1 inhibitors. MATERIALS AND METHODS: Two esophageal
      adenocarcinoma cell lines (SEG-1 and BIC) and two esophageal squamous cell cancer
      lines (KYSE 150 and KYSE 410) were treated with rofecoxib at doses ranging from
      8.0 to 125 microg/well. NS-398 (a COX-2 antagonist) and Catechin (a COX-1
      antagonist) were also used at doses of 50 and 100 microM. Esophageal cell
      viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated after 18 h
      of incubation with rofecoxib, NS398, and Catechin by flow cytometry via annexin V
      assay. RESULTS: Rofecoxib, NS-398, and Catechin treatments all resulted in
      significant antiproliferative effects in both adenocarcinoma and squamous cell
      carcinoma of the esophagus in vitro. Substantial increases in apoptotic activity
      were also found in all cell lines. CONCLUSIONS: Our findings suggest that COX-2
      and COX-1 inhibition has potential to become an effective treatment for both
      histological variants of esophageal cancer. Further in vivo and human studies are
      warranted to evaluate the safety and clinical utility of these agents in patients
      with all cancers of the esophagus.

PMID- 15145697
TI  - Inflammatory mediators and growth factors in obstructive renal injury.
AB  - Obstruction of the upper urinary tract poses a significant clinical challenge to
      the urologist, and the cascade of renal cellular and molecular events triggered
      by upper urinary tract obstruction result in a progressive, and eventually
      permanent, loss in renal function. These pathological changes include the
      development of renal fibrosis, tubular atrophy, interstitial inflammation, and
      apoptotic renal cell death. A myriad of cytokines and growth factors have been
      identified as major contributors to obstruction-induced renal fibrosis and
      apoptotic cell death, including transforming growth factor-beta1, angiotensin II,
      nuclear factor-kappaB, and tumor necrosis factor-alpha. This review examines the
      role of these mediators in obstruction-induced renal injury.

PMID- 15145698
TI  - Basic science: why do we do it?

PMID- 15145699
TI  - Selective inhibition of anandamide cellular uptake versus enzymatic hydrolysis--a
      difficult issue to handle.
AB  - There is considerable debate at present as to whether the uptake of anandamide
      (AEA) into cells is by a facilitated transport process or by passive diffusion
      driven by fatty acid amide hydrolase (FAAH). The possibility that both processes
      occur, but to different extents depending upon the cell type used, has been
      difficult to investigate pharmacologically since available compounds show little
      selectivity between inhibition of AEA uptake and inhibition of FAAH. Recently,
      three compounds, UCM707 [N-(Fur-3-ylmethyl)arachidonamide], OMDM-1 and OMDM-2
      [the 1'-(S)- and 1'-(R)-enantiomers of the 1'-4-hydroxybenzoyl analogue of
      oleoylethanolamide], selective for the uptake process, have been described and we
      have used these compounds, together with AM404 [(N-(4-hydroxyphenyl) arachidonoyl
      amide)] and VDM11 [(5Z,8Z,11Z,14Z)-N-(4-Hydroxy-2-methylphenyl)-5,8,11,14
      eicosatetraenamide]), with the initial aim of determining which mechanism of
      uptake predominates in C6 glioma and RBL-2H3 cells. AM404 and VDM11 were both
      found to decrease the uptake of 2 microM AEA into cells (IC50 values 6-11
      microM), but they also inhibited rat brain FAAH (IC50 values 1-6 microM).
      However, when using a different FAAH assay protocol, VDM11 was a much less potent
      FAAH inhibitor (IC50>50 microM) regardless of the cell type and animal species
      used. In contrast, we confirmed that UCM707, OMDM-1 and OMDM-2 were weak
      inhibitors of FAAH (IC50 values >50 microM) under all conditions used. However,
      their potency as inhibitors of AEA cellular accumulation appears to be largely
      dependent on the cell type and assay conditions used. In particular, the potency
      of UCM707 (IC50 value > or =25 microM) was considerably lower than the
      submicromolar potency previously reported for U937 cells. It is concluded that
      the cause/effect relationship between AEA uptake and hydrolysis cannot be
      investigated uniquely by using supposedly selective inhibitors of each process.

PMID- 15145700
TI  - Nitric oxide activates glibenclamide-sensitive K+ channels in urinary bladder
      myocytes through a c-GMP-dependent mechanism.
AB  - In the present investigation, we used standard patch clamp techniques to test
      whether nitric oxide (NO) generation has any role to play with either activation
      or inhibition of ATP-sensitive (KATP) channels in guinea-pig urinary bladder. We
      found that NO generation leads to activation of KATP channels through a cyclic
      guanosine monophosphate (c-GMP)-dependent protein kinase. 3-Morpholinosydnonimine
      (SIN, 100 microM) potentiated activation of an inward current in whole cell patch
      clamp experiments. Glibenclamide (10 microM) and 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ, 10 microM) inhibited the SIN-activated current. Both in
      cell-attached and in inside out patches, SIN (200 microM) potentiated KATP
      channel activity, and the increased channel activity in inside out patches was
      suppressed by glibenclamide (50 microM), ATP (1 mM) and (9s,10R,12R)
      2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12,-epoxy-1H
      diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6] benzodiazocine-10-carboxylic
      acid, methyl ester (KT-5823, 10 nM). 8-Br-cGMP (100 microM) increased the KATP
      channel activity in cell-attached patches, and this was suppressed by
      glibenclamide (50 microM). These results suggest that the NO-c-GMP-PKG pathway
      contributes to activation of K(ATP) channels in guinea-pig urinary bladder
      myocytes.

PMID- 15145701
TI  - Novel analogs of the sigma receptor ligand BD1008 attenuate cocaine-induced
      toxicity in mice.
AB  - Previous studies have shown that BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl
      2-(1-pyrrolidinyl)ethylamine) and related analogs attenuate the toxicity and
      stimulant effects of cocaine through antagonism of sigma receptors. In the
      present study, six analogs of BD1008 (UMB 98-103) were synthesized and evaluated
      in receptor binding and behavioral studies. Competition binding studies confirmed
      that all six compounds have high affinity for sigma1 receptors, moderate affinity
      for sigma2 receptors, and low to negligible affinity for monoamine transporters,
      opioid, N-methyl-D-aspartate, dopamine, and 5-HT receptors. In behavioral
      pharmacological studies, pretreatment of mice with UMB 100, UMB 101, or UMB 103
      significantly attenuated cocaine-induced convulsions and lethality. Together with
      earlier studies, the data suggest that analogs of BD1008 are promising medication
      development leads for reducing the toxicity of cocaine.

PMID- 15145702
TI  - Comparison of the antinociceptive effect of morphine, methadone, buprenorphine
      and codeine in two substrains of Sprague-Dawley rats.
AB  - Sprague-Dawley rats from two different vendors, Mollegard, Denmark and B&K
      Universal, Sweden, have been tested for the antinociceptive effect of morphine,
      methadone, buprenorphine and codeine on the hot plate. Morphine and methadone had
      significantly weaker effect in Mollegard rats compare to B&K rats. In contrast,
      the effect of buprenorphine was stronger in Mollegard rats than in B&K rats and
      the effect of codeine was similar in the two substrains. Plasma levels of
      morphine, morphine-6-glucuronide, morphine-3-glucuronide, buprenorphine and
      norbuprenorphine were determined at two time points after drug injection.
      Mollegard rats had significantly lower mean plasma level of morphine and
      significantly higher ratio of morphine-3-glucuronide/morphine at 30 min, compared
      to B&K rats. No difference was seen for the metabolism of buprenorphine in the
      two substrains. The results suggest that Mollegard rats metabolize morphine to
      morphine-3-glucuronide to a greater extent than B&K rats, and this may at least
      partly underlie the substrain difference in the effect of morphine. It is also
      suggested that the antinociceptive mechanisms of buprenorphne may be different
      from those of morphine and methadone.

PMID- 15145703
TI  - Riboflavin reduces hyperalgesia and inflammation but not tactile allodynia in the
      rat.
AB  - Vitamin B2 (riboflavin) has been proposed as a prophylactic therapy of migraine.
      However, so far there are no preclinical studies about the analgesic properties
      of this vitamin. The current study was designed to investigate the possible
      antinociceptive, antihyperalgesic and antiallodynic effect of riboflavin in
      formalin, carrageenan-induced thermal hyperalgesia, and spinal nerve ligation
      models, respectively. Oral riboflavin produced a dose-related antinociceptive
      (6.25-50 mg/kg), antihyperalgesic (25-150 mg/kg) and anti-inflammatory (50-150
      mg/kg) effect. Gabapentin (100 mg/kg, positive control), but not riboflavin (150
      600 mg/kg), reduced tactile allodynia in neuropathic rats. Riboflavin-induced
      antinociception in the formalin test was reversed by pretreatment with NG-L-nitro
      arginine methyl ester and glibenclamide, but not by NG-D-nitro-arginine methyl
      ester or naloxone. Our results indicate that riboflavin is able to produce
      antinociception and anti-inflammatory, but not antiallodynic, effect in the rat.
      The effect of riboflavin could be due to the activation of K+ channels or nitric
      oxide release, but not activation of opioid mechanisms.

PMID- 15145704
TI  - Serotonin transporter in substance P (neurokinin 1) receptor knock-out mice.
AB  - We recently demonstrated that mice lacking the gene for substance P (neurokinin
      1) receptors (NK1-/-) show improved cortical dialysate serotonin (5-HT) responses
      to paroxetine [J. Neurosci. 21 (2001) 8188]. To test for changes that may involve
      the 5-HT transporter (5-HTT) in these mutant mice, in vivo/in vitro studies were
      performed. Autoradiographic quantification of 5-HTT was performed: [3H]citalopram
      binding did not reveal any modification of 5-HT binding sites in the dorsal raphe
      nucleus (DRN) of wild-type NK1+/+ control and mutant NK1-/- mice. These results
      were further confirmed by 5-HTT mRNA quantification using competitive reverse
      transcription and polymerase chain reaction (RT-PCR) assay, which showed similar
      messenger levels in the DRN of both mice genotypes. The functional status of 5
      HTT in vivo was tested by using the zero net flux method of quantitative
      microdialysis in two serotonergic nerve terminal regions, the frontal cortex and
      ventral hippocampus, of wild-type NK1+/+ and NK1-/- mice. Neither basal
      extracellular 5-HT levels nor the 5-HT extraction fraction of the probe (Ed an
      index of 5-HT uptake in vivo) differed between wild-type and mutant mice in the
      two brain regions studied. These results suggest that no compensatory response to
      the constitutive deletion of the tachykinin NK1 receptor involving changes in the
      activity of the selective 5-HT transporter occurred in the DRN, frontal cortex
      and ventral hippocampus in mice.

PMID- 15145705
TI  - The role of intraspinal adenosine A1 receptors in sympathetic regulation.
AB  - Using a splanchnic nerve-spinal cord preparation in vitro, we have previously
      demonstrated that tonic sympathetic activity is generated from the thoracic
      spinal cord. Here, we sought to determine if adenosine receptors play a role in
      modulating this spinally generated sympathetic activity. Various adenosine
      analogs were applied. N6-Cyclopentyladenosine (CPA, adenosine A1 receptor
      agonist) and 5'-N-ethylcarboxamidoadenosine (NECA, adenosine A1/A2 receptor
      agonist) reduced, while N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA, non
      selective adenosine A3 receptor agonist) did not alter sympathetic activity. The
      inhibitory effect of CPA or NECA on sympathetic activity was reversed by 8
      cyclopentyltheophylline (CPT, adenosine A1 receptor antagonist) or abolished by
      CPT pretreatment. In the presence of 3,7-dimethyl-1-propargylxanthine (DMPX,
      adenosine A2 receptor antagonist), sympathetic activity was still reduced by CPA
      or NECA. Sympathetic activities were not changed by applications of the more
      selective adenosine A2 or A3 receptor agonists or antagonists, including 4-[2-[[6
      amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2
      yl]amino]ethyl]benzenepropanoic acid (CGS21680), 4-(2-[7-amino-2-(2
      furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385), 2
      chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Chloro-IB-MECA), and 3
      ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5
      dicarboxylate (MRS1191). These findings exclude a possible involvement of A2 or
      A3 receptors in sympathetic regulation at the spinal levels. Interestingly, CPT
      alone did not affect sympathetic activity, suggesting that adenosine A1 receptors
      are endogenously quiescent under our experimental conditions. We conclude that
      intraspinal adenosine A1 receptors may down-regulate sympathetic outflow and
      serve as a part of the scheme for neuroprotection.

PMID- 15145706
TI  - Zinc treatment induces cortical brain-derived neurotrophic factor gene
      expression.
AB  - Most of antidepressants induce expression of the gene coding for brain-derived
      neurotrophic factor (BDNF) in the hippocampal/cortical neurons. Recent data
      indicate antidepressant-like activity of zinc in animal models. We now report
      that chronic treatment with zinc induced an increase in cortical but not
      hippocampal BDNF mRNA level (Northern blot). Tranylcypromine, a classic
      antidepressant, increased BDNF mRNA level in both examined brain regions. This is
      the first demonstration that zinc increases the BDNF gene expression, which is
      the effect shared by most of clinically effective antidepressants.

PMID- 15145707
TI  - Long-term imipramine withdrawal induces a depressive-like behaviour in the forced
      swimming test.
AB  - Chronic antidepressant treatments enhance dopaminergic neurotransmission in the
      mesolimbic dopamine system. We suggested that this potentiation might underlie
      both the antidepressant therapeutic effect and the antidepressant-induced switch
      from depression to mania. In a recent study we have shown a reversal of the
      imipramine-induced dopaminergic supersensitivity after 40 days of chronic
      imipramine withdrawal. We interpreted this result suggesting that the mood
      switches observed in bipolar patients following antidepressant treatment and
      subsequent withdrawal, i.e. mania followed by rebound depression, might depend
      upon parallel changes in the mesolimbic dopamine system sensitivity. On this
      basis, one might predict a depressive-like behaviour after long-term interruption
      of a chronic treatment with imipramine. To test this hypothesis we examined the
      behaviour of rats treated with chronic imipramine 40 days after treatment
      interruption in an animal model of depression, the forced swimming test. The
      results show that animals treated with chronic imipramine, 40 days after
      treatment interruption, display a depressive-like behaviour in the forced
      swimming test, as indicated by their increased immobility with respect to the
      control group.

PMID- 15145708
TI  - cAMP-independent mechanism is significantly involved in beta2-adrenoceptor
      mediated tracheal relaxation.
AB  - The role of cAMP in the beta2-adrenoceptor-mediated relaxation in response to
      salbutamol was examined in guinea pig tracheal smooth muscle. The concentration
      dependent salbutamol-induced relaxation was antagonized in a competitive fashion
      by a beta2-selective adrenoceptor antagonist, butoxamine, with a pA2 value of
      6.90. Salbutamol (10 microM) elevated the tracheal smooth muscle cAMP content by
      about fivefold, a response which was significantly inhibited by an adenylyl
      cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536, 100
      microM). However, the salbutamol-elicited relaxation was not diminished by SQ
      22,536 (100 microM). These results provide evidence for the first time that a
      cAMP-independent mechanism(s) is involved in beta2-adrenoceptor-mediated tracheal
      smooth muscle relaxation in the guinea pig.

PMID- 15145710
TI  - HEART: an automated beat-to-beat cardiovascular analysis package using Matlab.
AB  - A computer program is described for beat-to-beat analysis of cardiovascular
      parameters from high-fidelity pressure and flow waveforms. The Hemodynamic
      Estimation and Analysis Research Tool (HEART) is a post-processing analysis
      software package developed in Matlab that enables scientists and clinicians to
      document, load, view, calibrate, and analyze experimental data that have been
      digitally saved in ascii or binary format. Analysis routines include traditional
      hemodynamic parameter estimates as well as more sophisticated analyses such as
      lumped arterial model parameter estimation and vascular impedance frequency
      spectra. Cardiovascular parameter values of all analyzed beats can be viewed and
      statistically analyzed. An attractive feature of the HEART program is the ability
      to analyze data with visual quality assurance throughout the process, thus
      establishing a framework toward which Good Laboratory Practice (GLP) compliance
      can be obtained. Additionally, the development of HEART on the Matlab platform
      provides users with the flexibility to adapt or create study specific analysis
      files according to their specific needs.

PMID- 15145709
TI  - Evidence for hypothalamic K+(ATP) channels in the modulation of glucose
      homeostasis.
AB  - Several lines of evidence support the hypothesis that ATP-sensitive K+ channels
      (K+(ATP)) participate in the brain's regulation of peripheral glucose
      homeostasis. In testing this hypothesis we conducted a series of in vivo
      experiments using albino rats and bilateral intrahypothalamic injections of
      K+(ATP) channel blockers, glibenclamide and repaglinide. The results show that
      0.2 and 2.0 nM injections of glibenclamide lowered blood glucose in a dose
      dependent manner. During mild insulin-induced hypoglycemia, hypothalamic
      glibenclamide delayed recovery to normoglycemia. The impaired recovery was
      associated with a reduction in plasma norepinephrine (P<0.001), though
      circulating epinephrine and glucagon were not reduced. In a separate experiment,
      2-deoxy-D-glucose (200 mg/kg) was intraperitoneally administered to produce
      neuroglucopenia. Hypothalamic injections of either glibenclamide or repaglinide
      significantly blunted compensatory hyperglycemic responses (P<0.01). In a feeding
      study, 2.0, but not 0.2 nM of hypothalamic glibenclamide, reduced chow intake
      over a 2-h period (P<0.01). The results support the hypothesis that hypothalamic
      K+(ATP) channels participate in central glucose-sensing and glucose regulation.

PMID- 15145711
TI  - Classification of carotid artery stenosis of patients with diabetes by neural
      network and logistic regression.
AB  - The blood flow hemodynamics of carotid arteries were obtained from carotid
      arteries of 168 individuals with diabetes using the 7.5 MHz ultrasound Doppler M
      unit. Fast Fourier Transform (FFT) methods were used for feature extraction from
      the Doppler signals on the time-frequency domain. The parameters, obtained from
      the Doppler sonograms, were applied to the mathematical models that were
      constituted to analyze the effect of diabetes on internal carotid artery (ICA)
      stenosis. In this study, two different mathematical models such as the
      traditional statistical method based on logistic regression and a Multi-Layer
      Perceptron (MLP) neural network were used to classify the Doppler parameters. The
      correct classification of these data was performed by an expert radiologist using
      angiograpy before they were executed by logistic regression and MLP neural
      networks. We classified the carotid artery stenosis into two categories such as
      non-stenosis and stenosis and we achieved similar results (correctly classified
      (CC) = 92.8%) in both mathematical models. But, as the degree of stenosis had
      been increased to 4 (0-39%, 40-59%, 60-79% and 80-99% diameter stenosis), it was
      found that the neural network (CC = 73.9%) became more efficient than the
      logistic regression analysis (CC = 67.7%). These outcomes indicate that the
      Doppler sonograms taken from the carotid arteries may be classified successfully
      by neural network.

PMID- 15145712
TI  - Intelligent training system integrated in an echocardiography simulator.
AB  - Computer simulators play an important role in medical education. We have extended
      our simulator EchoComJ with an intelligent training system (ITS) to support
      trainees adjusting echocardiographic standard views. EchoComJ is an augmented
      reality application that combines real three-dimensional ultrasound data with a
      virtual heart model enabling one to simulate an echocardiographic examination.
      The ITS analyzes the image planes according to their position, orientation and
      the visualization of anatomical landmarks using fuzzy rules. An adaptive feedback
      is provided that colors the specific anatomic landmarks within the contours of
      the virtual model based on the quality of the image plane.

PMID- 15145713
TI  - An environment for knowledge discovery in biology.
AB  - This paper describes a data mining environment for knowledge discovery in
      bioinformatics applications. The system has a generic kernel that implements the
      mining functions to be applied to input primary databases, with a warehouse
      architecture, of biomedical information. Both supervised and unsupervised
      classification can be implemented within the kernel and applied to data extracted
      from the primary database, with the results being suitably stored in a complex
      object database for knowledge discovery. The kernel also includes a specific high
      performance library that allows designing and applying the mining functions in
      parallel machines. The experimental results obtained by the application of the
      kernel functions are reported.

PMID- 15145714
TI  - Apoptosis: an optimization approach.
AB  - The present study examined the levels of procaspases (zymogens of the main
      apoptosis enzymes, caspases) that are predicted based on application of the
      optimization principle. Optimization models have previously been successfully
      developed for many other physiological systems (e.g., circulation, oxygen
      transport system, fibrinolysis, and blood coagulation) but have not previously
      been applied to apoptotic biochemical pathways. Our model assumed that apoptotic
      pathways are designed to minimize protein consumption. Procaspase concentrations
      were predicted based on this assumption, along with known schemes of apoptosis
      reactions and kinetic constants for procaspase activation and target cleavage.
      Good agreement between the model predictions and actual procaspase levels was
      observed.

PMID- 15145715
TI  - Percutaneous vertebroplasty: history, technique and current perspectives.
AB  - Percutaneous vertebroplasty is a safe and efficacious technique for the treatment
      of persistent pain from a fractured vertebral body. Injection of cement into the
      vertebral body is made after insertion of a large-bore needle, frequently by a
      trans-pedicular approach. Vertebroplasty is most commonly used to treat painful
      osteoporotic fracture resistant to conservative therapy, but may be helpful in
      other conditions such as malignant collapse. NICE guidelines are now available
      for this procedure, which is relatively new in the UK, but has been performed for
      more than 15 years in continental Europe.

PMID- 15145716
TI  - Medical interventional procedures-reducing the radiation risks.
AB  - Over the last 40 years, the number of percutaneous interventional procedures
      using radiation has increased significantly, with many secondary care clinicians
      using fluoroscopically guided techniques. Many procedures can deliver high
      radiation doses to patients and staff, with the potential to cause immediate and
      delayed radiation effects. The challenge for interventionists is to maximize
      benefit, whilst minimizing radiation risk to patients and staff. Non-radiologist
      clinicians are often inadequately trained in radiation safety and radiobiology.
      However, clinical governance and legislation now requires a more rigorous
      approach to protecting patients and staff. Protection can be ensured, and risks
      can be controlled, by appropriate design, procurement and commissioning of
      equipment; quality assurance; and optimal operational technique, backed by audit.
      Interventionists need knowledge and skills to reduce the risks. Appropriate
      training should include awareness of the potential for radiation injury,
      equipment operational parameters, doses measurement and recording methods and
      dose reduction techniques. Clinical governance requires informed consent,
      appropriate patient counselling and follow-up.

PMID- 15145717
TI  - Calvarial masses of infants and children. A radiological approach.
AB  - Children frequently present with asymptomatic head lumps that have been
      discovered by their parents or by their hairdressers. Other children present with
      painful lumps or symptoms of intra-cranial masses with calvarial involvement.
      Imaging plays an important role in the diagnosis of such masses and in subsequent
      surgical planning. We present a review of the types of lesion that may present in
      these ways.

PMID- 15145718
TI  - Imaging of gastrointestinal stromal tumour (GIST).
AB  - Gastrointestinal stromal tumour (GIST) represents the most common kind of
      mesenchymal tumour that arises from the alimentary tract. GIST is currently
      defined as a gastrointestinal tract mesenchymal tumour containing spindle cells
      (or less commonly epithelioid cells or rarely both) and showing CD117 (c-kit
      protein) positivity. Targeted molecular therapy of non-resectable GIST using
      imatinib, a specific tyrosine kinase receptor inhibitor, represents a real
      milestone in the management of solid malignancy. Imaging studies, both anatomical
      and functional, are playing an increasingly important role in management of
      patients with GIST. This review illustrates the radiological appearance of GISTs
      and the site-specific roles of each imaging tool. Clinical features and
      radiological differential diagnosis of GIST are also discussed.

PMID- 15145719
TI  - Comparison of special interest computed tomography, endosonography and
      histopathological stage of oesophageal cancer.
AB  - AIMS: To assess the strength of agreement between the perceived pre-operative
      stage of oesophageal tumours as determined by spiral computed tomography (CT) and
      endoscopic ultrasound (EUS), both alone and in combination, with the
      histopathological stage. METHODS: Sixty patients with oesophageal cancer
      underwent both pre-operative CT and EUS performed by two consultant radiologists
      with a special interest in upper gastrointestinal radiology. The strength of the
      agreement between the radiological stage and the histopathological stage was
      determined by means of the weighted Kappa statistic (Kw). RESULTS: Sensitivity
      for T and N stages was 58% and 79% for CT, and 72% and 91% for EUS. Specificity
      for T and N stages was 80% and 84% for CT, and 85% and 68% for EUS. Kw for T and
      N stages was 0.455 (p=0.0001) and 0.603 (p=0.0001) for CT compared with 0.604
      (p=0.0001) and 0.610 (p=0.0001) for EUS. In patients when CT and EUS agreed
      regarding the T and N stages, the strength of agreement between the radiological
      and the histopathological stage was greater (Kw T 0.613 (p=0.0001), Kw N 0.781
      (p=0.0001)). CONCLUSION: CT and EUS are complimentary techniques for the staging
      of oesophageal tumours, and these results reinforce the importance of specialist
      radiology in stage directed management.

PMID- 15145720
TI  - Immune reconstitution inflammatory syndrome in HIV-infected patients with
      mycobacterial infections starting highly active anti-retroviral therapy.
AB  - AIM: To describe the radiological appearances of immune reconstitution
      inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected
      patients with mycobacterial infections starting highly active anti-retroviral
      therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients
      with IRIS due to mycobacterial infection were studied. Intercurrent infection and
      poor drug compliance were excluded as causes of presentation. The chest
      radiological appearances at the time of starting HAART and at the time of
      diagnosis of IRIS were compared. RESULTS: In these five patients there was
      clinical and radiological deterioration, occurring between 10 days and 7 months
      after starting HAART, leading to unmasking of previously undiagnosed
      mycobacterial infection or to worsening of mycobacterial disease. All five
      patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions
      in peripheral blood HIV "viral load". Chest radiographic abnormalities due to
      IRIS included marked mediastinal lymphadenopathy in three patients-severe enough
      to produce tracheal compression in two patients (one of whom had stridor)-and was
      associated with new pulmonary infiltrates in two patients. The other two patients
      had new infiltrates, which in one patient was associated with a pleural effusion.
      CONCLUSION: These cases illustrate the diverse chest radiographic appearances of
      IRIS occurring after HAART in patients with mycobacterial and HIV co-infection.
      Marked mediastinal lymphadenopathy occurred in three of these five patients (with
      associated tracheal narrowing in two patients); four patients developed pulmonary
      infiltrates and one had an effusion. The cases further highlight that the onset
      of IRIS may be delayed for several months after HAART is started.

PMID- 15145721
TI  - Pericardial abscess occurring after tuberculous pericarditis: image morphology on
      computed tomography and magnetic resonance imaging.
AB  - AIM: To study the image morphology on computed tomography (CT) and magnetic
      resonance imaging (MRI) of pericardial abscess, an uncommon complication of
      tuberculous pericarditis. MATERIAL AND METHODS: In a 9-year period, 120 patients
      with clinical and imaging features of constrictive pericarditis were
      retrospectively reviewed. Of them, 13 patients (age range, 1-51 years; seven
      females, six males), who had a pericardial mass on echocardiography, and were
      subjected to CT (11 patients) and MRI (7 patients), were included as subjects of
      the present study. Five patients underwent both the investigations. The intra
      lesional morphology, location, extent, mass effect on adjacent cardiac chambers,
      secondary effects on the atria and venae cavae, and pericardial thickness were
      studied. Histopathological confirmation of tubercular infection was available in
      nine patients. In the remaining four patients, the diagnosis was based on typical
      extra-cardiac manifestations of tuberculosis. RESULTS: A total of 15 abscesses
      were detected. CT showed a lesion with a hypodense core and an enhancing rim in
      all patients. On spin-echo T1-weighted MRI, 57% of the paients had a lesion with
      a hyperintense core, suggesting an exudative process. Seventy-one percent of
      patients showed a lesion with a hyperintense core on T2-weighted MRI, while one
      lesion was hypointense. Post-gadolinium MRI was performed in two patients and
      showed an enhancing rim in both, with enhancing septa in one. The predominant
      site of involvement was in the right atrioventricular (AV) groove (77%).
      Localized tamponade, suggested by the presence of mass effect on an adjacent
      cardiac chamber, was noted in nine (69%) cases, with proximal atrial dilatation
      in 78% of them. Four other patients (31%) had atrial dilatation without a
      localized mass effect. CONCLUSION: Pericardial abscess is an uncommon
      complication of constrictive pericarditis. Tuberculosis was responsible for
      abscess formation in all cases in this study. The majority of the lesions are
      located in the right AV groove with imaging features suggestive of localized
      tamponade. The presence of a hypointense core on T2-weighted MRI may suggest a
      tubercular aetiology.

PMID- 15145722
TI  - Uterine artery embolization for adenomyosis without fibroids.
AB  - AIM: To evaluate the potential usefulness of transcatheter uterine artery
      embolization as a treatment for symptomatic adenomyosis in patients without
      uterine fibroids. MATERIALS AND METHODS: Uterine artery embolization using
      polyvinyl alcohol particles sized 250-710 mm was performed in 43 patients (mean;
      40.3 years, range; 31-52 years) with dysmenorrhoea, menorrhagia, or bulk-related
      symptoms (pelvic heaviness, urinary frequency) due to adenomyosis without
      fibroids. All patients underwent pre-procedural and 3.5 months (range 1-8 months)
      follow-up magnetic resonance imaging (MRI) with contrast enhancement. Clinical
      symptoms were also assessed at the time of MRI before and after embolization.
      RESULTS: Significant improvement of dysmenorrhoea (95.2%) and menorrhagia (95.0%)
      was reported in most patients. Contrast-enhanced MRI revealed non-enhancing areas
      suggesting coagulation necrosis of adenomyosis in 31 patients (72.1%), decreased
      size without necrosis in 11 patients (25.6%), and no change in one patient
      (2.3%). The mean volume reduction of the uteri after uterine artery embolization
      was 32.5% (from 321.7+/-142.9 to 216.7+/-130.1 cm(3)). CONCLUSION: Transcatheter
      uterine artery embolization is an effective therapy for the treatment of
      symptomatic pure adenomyosis, and may be a valuable alternative to hysterectomy.

PMID- 15145723
TI  - Subintimal recanalisation and stenting of a common iliac artery occlusion by a
      left axillary and an ipsilateral femoral retrograde approach using modified
      gooseneck grab aided by balloon dilatation of "dissection port".
AB  - The technique of recanalisation using deliberate subintimal dissection of an
      occluded iliac artery is being increasingly used and practised via ipsilateral
      and or contralateral approaches. There remains, however, a fair proportion of
      cases where, in spite of using gooseneck snares, the wire manipulation to
      traverse the occlusion can prove unsuccessful resulting in failed de-obliteration
      of the occlusion. We describe a technique to aid successful re-establishment of
      the patency using balloon dilatation of the dissection "entry port" with modified
      gooseneck snare grab.

PMID- 15145724
TI  - Subacute cerebellar infarct mimicking meningioma.

PMID- 15145725
TI  - MRI of non-puerperal uterine inversion due to endometrial carcinoma.

PMID- 15145726
TI  - When and how nasolacrimal polyurethane stents should be removed?

PMID- 15145728
TI  - The diagnostic contribution of the frontal lumbar spine radiograph in community
      referred low back pain.

PMID- 15145730
TI  - A personal view.

PMID- 15145731
TI  - A reconstructive algorithm for plastic surgery following extensive chest wall
      resection.
AB  - Chest wall reconstruction following extensive resection is greatly facilitated by
      the use of vascularised flaps and prosthetic material. Plastic surgeons are often
      asked to assist with coverage of large chest wall defects. However, in addition
      to soft tissue coverage, we need to address other important issues such as the
      status of the pleural cavity, and the requirement for skeletal support. The
      purpose of this report is to analyse our experience, provide a reconstructive
      algorithm following the ablative procedure and review the literature. Two hundred
      chest wall resections were performed from 1975 to 2000. Defect location was
      divided into anterior (n = 73) lateral (n = 36) anterior-lateral (n = 36)
      posterior-lateral (n = 19) posterior (n = 22) and forequarter (n = 14) Average
      number of ribs resected was four. One hundred and fifty-eight patients (79%)
      required chest wall reconstruction with either prosthetic material and/or flap
      closure. Mesh closure was required in 85 cases (43%), being highest for lateral
      defects (61%), and lowest for anterior defects (31%). Vascularised flaps were
      needed in 112 patients (56%), more common in anterior defects (79%), and less
      common for the posterior-lateral defects (26%). Inpatient complication rate was
      27% (43/158) following reconstruction, with a mortality of 6% (10/158). Chest
      wall reconstruction is common following extensive resection. This includes
      management of the pleural cavity, skeletal support and soft tissue coverage. A
      better understanding of the respiratory mechanics and local thoracoabdominal
      anatomy is crucial for managing these complex defects. The need for skeletal
      support was more prevalent in lateral and posterior-lateral defects. Flap
      reconstruction was required more often to cover large anterior defects, with
      regional flaps predominating.

PMID- 15145732
TI  - Pulsed dye laser therapy for rosacea.
AB  - Rosacea is a chronic and progressive inflammatory skin disorder affecting the
      facial convexities for which no curative measure is currently available. Forty
      consecutive patients with rosacea were treated with the Cynosure PhotoGenica V
      pulsed dye laser. The improvement following laser therapy was assessed according
      to a sliding scale: 1 (worse after treatment), 2 (no improvement), 3 (slight
      improvement), 4 (moderate improvement), 5 (marked improvement). Following an
      average of 2.4 (range 1-10) laser treatments, a mean score of 4.4 and 4.3 for
      overall improvement was achieved as judged by the patients and independently
      assessed by a family member or a close friend of the patients, respectively. The
      response of erythema and telangiectasia to laser therapy, evaluated by an
      independent panel of 10 members, showed a mean score of 3.7. Three patients
      experienced an exacerbation of rosacea during the treatment period requiring
      antibiotic therapy. During the follow-up period of 6.0-55.5 (mean, 23.3) months
      after completion of laser therapy, no patient (including 13 patients in whom
      papulation and pustulation which were amongst the presenting symptoms) required
      medical treatment. Six patients developed post-inflammatory hyper-pigmentation
      necessitating skin bleach but no other complication such as scarring was
      observed. Three patients reported that the residual erythema had progressed after
      an initial improvement during follow-up periods of 52.4, 15.8 and 6.0 months. All
      patients felt that laser therapy was worthwhile. We conclude that pulsed dye
      laser therapy is a useful treatment for rosacea.

PMID- 15145733
TI  - Revision anterior submuscular transposition of the ulnar nerve for failed
      subcutaneous transposition.
AB  - We evaluated the results of revision surgery for persistent cubital tunnel
      syndrome after failed surgical treatment. Eighteen patients were evaluated with
      an average age of 44 years. The majority of the primary procedures were
      subcutaneous transpositions (15 patients). The average follow-up time was 34
      months. All patients were treated with a submuscular transposition of the ulnar
      nerve and Z-lengthening of the flexor-pronator origin. The most common operative
      findings were perineural scarring (16), retained medial intermuscular septum (10)
      and common flexor aponeurosis (9). Pre-operative and post-operative data were
      compared. The majority of patients improved their postoperative grade and their
      ability to do daily activities or work and stated that the surgery met some or
      all of their expectations. Most patients had partial relief of their pain and the
      satisfaction rate was 78%. Our study suggests that although these results are
      less favorable than those for the primary procedure, submuscular transposition is
      a useful technique for revision of failed cubital tunnel syndrome surgery.

PMID- 15145734
TI  - The effect of single administration of vascular endothelial growth factor or L
      arginine on necrosis and vasculature of the epigastric flap in the rat model.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) and nitric oxide (NO)
      produce vasodilation, induce angiogenesis, and improve survival of surgical
      flaps. We used the rat epigastric skin flap to study the effect of a single intra
      arterial dose of VEGF or L-arginine, a substrate for NO production, on flap
      regional necrosis and pedicle dependence of flap perfusion. METHODS: In 30
      Sprague-Dawley rats an 8 x 8 cm2 skin flap, consisting of four vertical zones
      marked A through D (right to left), based on the proximal right inferior
      epigastric vessels was raised. Subsequently, 1 ml of either saline (control, n
      =10), 5 microg VEGF (VEGF, n = 10), or 50 mg of L-arginine (L-arginine, n = 10)
      was injected into the arterial pedicle by cannulating the right saphenous artery,
      and the flap was resutured in place. After 8 days, the animals were perfused
      systemically with 15 microm coloured fluorescent microspheres before (blue) and
      after (yellow-green) ligation of the right inferior epigastric vascular pedicle.
      After sacrifice, the area of flap necrosis was measured in each zone by templates
      and weight-to-surface ratio, and the flap zones were harvested and processed for
      determination of fluorescence and blood flow. RESULTS: Administration of VEGF or
      L-arginine resulted in decreased total and regional (zone D) flap necrosis (ANOVA
      <0.001). The total and regional flap shrinkage was greater in the experimental
      groups (ANOVA <0.02). While VEGF and L-arginine decreased the percentage of
      necrosis in the zone most distal to the pedicle (ANOVA <0.01) only L-arginine
      diminished percentage of total flap necrosis (p = 0.04). In the VEGF group, total
      and regional flap perfusion did not change after pedicle ligation, but perfusion
      decreased significantly in zones B through D in the L-arginine treated rats.
      CONCLUSION: Single intra-pedicle administration of VEGF or L-arginine decreased
      necrosis of the epigastric skin flap at 8 days postoperatively, but flap
      shrinkage also increased in the zone with the greatest degree of necrosis.
      Perfusion data suggest that beneficial effects of VEGF and L-arginine on flap
      survival may be based on different mechanisms.

PMID- 15145736
TI  - Secondary reconstruction of asymmetric volume deficits of the lips: a transverse
      twist flap technique.
AB  - The reconstructive surgeon, dealing with both congenital anomalies such as
      clefts, and post-surgical or post-traumatic defects, may, on occasion be faced
      with a situation where there is either a unilateral deficit or excess of lip
      volume, or an asymmetry with bilateral volume inequalities. The classic examples
      of this are the characteristic whistle notch deformities sometimes seen after
      cleft-lip repairs. This paper presents another useful solution to such problems.
      The method involves the transposition of a transversely-oriented flap of mucosa,
      elevated on a connective tissue/muscle pedicle, and twisted or rotated 180
      degrees from the contralateral side of the lip, to help fill the defect. The flap
      is asymmetrical, thus enabling transposition of more tissue into the primary
      defect than is lost from the donor site. The principal advantage is that in a lip
      in which there is already an overall paucity of tissue, nothing further is
      discarded, while at the same time, tissue is replaced where it is most needed. A
      secondary benefit is that with proper design, the lip can be shortened from side
      to side and therefore filled out in the antero-posterior dimension. Technical
      details of the method are explained and the versatility of the technique is
      illustrated.

PMID- 15145735
TI  - The buccal fat pad in oral reconstruction.
AB  - We describe the indications, advantages, and complications of the buccal fat pad
      (BFP) flap and report our clinical experience with the flap for intraoral
      reconstruction after tumour removal. METHODS: From 1993 to 2002, a pedicled BFP
      flap was used to reconstruct oral defects after tumour removal in 15 patients,
      prospectively analysed. RESULTS: Adequate closure of the defect was achieved. In
      seven cases there was some retraction of the BFP. CONCLUSIONS: The BFP, as a
      flap, offers a good and simple option in the reconstruction of small to medium
      defects in the oral cavity, above all in older patients. The greatest
      disadvantage is that reduction in oral opening could occur, to an unpredictable
      degree.

PMID- 15145737
TI  - Other ways to use tissue expanded flaps.
AB  - Tissue expansion can arguably be regarded as one of the revolutions in
      reconstructive plastic surgery. Another three applications (illustrated by three
      case reports) for tissue expansion are presented.

PMID- 15145738
TI  - The gluteal perforator-based flap in repair of pressure sores.
AB  - The gluteal perforator-based flap is designed according to the localisation of
      sacral perforator vessels. These vessels penetrate the gluteus maximus muscle and
      reach the intrafascial and suprafascial planes, and the overlying skin forming a
      rich vascular plexus. The gluteal perforator-based flaps described in this paper
      are highly-vascularised, have minimal donor site morbidity, do not require the
      sacrifice of the gluteus maximus muscle and rarely lead to post-operative
      complications. We believe these easy-to-perform flaps might be considered as the
      first choice in the repair of gluteal pressure sores.

PMID- 15145739
TI  - Hirudo Medicinalis and the plastic surgeon.
AB  - Medicinal leech therapy is an ancient craft that dates back to ancient Egypt and
      the beginnings of civilisation. The popularity of Hirudo Medicinalis has varied
      throughout history, reaching such a peak in Europe in the early 19th century that
      supplies were exhausted. During the latter half of the 19th century, their use
      fell out of favour, as they did not fit in with the emerging concepts of modern
      medicine. Leeches have enjoyed a renaissance in the world of reconstructive
      microsurgery during recent years, and their first reported use in alleviating
      venous engorgement following flap surgery was reported in this journal [M
      Derganc, F Zdravic, Venous congestion of flaps treated by application of leeches,
      Br J Plast Surg 13 (1960) 187]. Contemporary plastic and reconstructive surgeons
      in units throughout the United Kingdom and Ireland continue to use leeches to aid
      salvage of failing flaps. We carried out a survey of all 62 plastic surgery units
      in the United Kingdom and the Republic of Ireland to assess the current extent of
      use, and to investigate current practice. We have shown that the majority of
      plastic surgery units in the UK and Ireland use leeches post-operatively and that
      the average number of patients requiring leech therapy was 10 cases per unit per
      year. Almost all units use antibiotic prophylaxis, but the type of antibiotic and
      combination used is variable. We outline current practice and suggest a protocol
      for the use of leeches. Whilst the use of leeches is widespread, the plastic
      surgery community has progressed little in defining indications for their use or
      in achieving an accepted protocol for their application in units throughout the
      UK and Ireland.

PMID- 15145740
TI  - Upper limb splints and the right to drive--who decides?
AB  - Management of upper limb pathology frequently requires the wearing of a splint
      for a period of time. Our Occupational Therapy Department fits approximately 2000
      thermoplastic splints per year. A significant number of these patients drive. In
      a bid to try and elucidate who is thought to have and who actually has
      responsibility for deciding which splints are safe to drive in we sent
      photographic questionnaires to patients, general practitioners (GPs), the police
      and driver and vehicle-licensing agency (DVLA). We performed a telephone survey
      of insurance companies. It is the duty of the patient to contact the DVLA if they
      have any doubt about their ability to drive safely whilst wearing the splint. Our
      results demonstrate only 10% of patients and 4% of GPs are aware of this. There
      was strong agreement between patients, GPs and the police about which splints
      would probably be safe to drive in, but patients need to be reviewed on an
      individual basis. Our study demonstrates a lack of knowledge among patients and
      GPs which could expose either group to adverse legal action in the event of an
      accident.

PMID- 15145742
TI  - Multicentric extra-abdominal desmoid tumours.
AB  - Despite their classification as benign, desmoid tumours are difficult to diagnose
      and manage. They are prone to recurrence and resection can be debilitating.
      Rarely, synchronous or metachronous multicentric desmoid tumours occur and may
      require further excision. Therefore, early detection of recurrence and
      multicentric tumours is vital. We present a case of metachronous desmoid tumours,
      and review the literature to propose a treatment pathway.

PMID- 15145741
TI  - Flow-through anterolateral thigh flap for a free osteocutaneous fibula flap in
      secondary composite mandible reconstruction.
AB  - Head and neck reconstruction after tumour ablation and radiotherapy often
      requires complex surgery. The need for free composite tissue transfer and the
      poor quality of the recipient site increase the level of difficulty
      substantially. We report a case in which the mandible, floor of the mouth and
      skin of the neck needed to be reconstructed in a heavily irradiated field. A
      single osteocutaneous fibula flap was insufficient to reconstruct the defect, and
      a free anterolateral thigh (ALT) flap was also used for external neck skin
      resurfacing. As the recipient vessels in the ipsilateral neck had been heavily
      irradiated the free ALT flap was used as an interposition conduit for the free
      osteocutaneous fibula flap enabling it to reach the healthy recipient vessels in
      the contralateral neck without needing vein grafts.

PMID- 15145743
TI  - Breast necrosis following harvest of internal mammary artery.
AB  - The use of internal mammary artery is well established not only in cardiac
      surgery for coronary artery bypass grafting but also in plastic surgery for
      breast reconstruction with free autologus tissue. The complications that follow
      harvest of internal mammary artery for heart surgery usually relate to the wound.
      This case report documents the first case of complete breast infarction following
      such a procedure in a patient who had no prior history of breast pathology. The
      histology of the breast showed extensive calcification of the intima and media of
      small to medium sized vessels, a condition called calciphylaxis, which is largely
      unknown outside the fields of nephrology and dermatology.

PMID- 15145744
TI  - Soft tissue augmentation with laparoscopically harvested omentum.

PMID- 15145745
TI  - Anatomical study of the lower-positioned transverse ligament.

PMID- 15145746
TI  - A possible new way of managing breast implant rippling using an autogenous fascia
      lata patch.

PMID- 15145747
TI  - A non-animal facial model for teaching local flaps to trainees.

PMID- 15145748
TI  - Controlling the stacking of cartilage grafts for nose tips.

PMID- 15145749
TI  - Coughing to distraction.

PMID- 15145750
TI  - Regulation of nestin expression after cortical ablation in adult rat brain.
AB  - During embryogenesis, transient expression of nestin in proliferating
      neuroepithelial stem cells signals the commitment of progenitor cells to
      differentiate. Although adult mammalian brain contains very little nestin,
      significant upregulation of nestin has been reported following cerebral injury,
      leading to speculation that nestin may be involved in brain repair. In this
      study, we assessed the temporal profile of nestin expression following ablation
      injury of the sensory barrel cortex and investigated the influence of
      contralateral whisker stimulation on nestin expression. Since the adult mammalian
      brain contains proliferating neuronal progenitor cells that can be labeled with
      bromodeoxyuridine (BrdU), we also determined the association of nestin
      reexpression with BrdU-labeled cells. Nestin reexpression was detected
      predominantly in the ipsilateral cortex 3 days post-ablation. There was no
      significant nestin upregulation in the subcortical region. Nestin reexpression
      was most marked surrounding the lesion, but also extended throughout the entire
      lateral cortex. Nestin in the ipsilateral cortex subsided by day 7, although
      perilesional nestin expression was still apparent 28 days post-injury. Western
      blot analysis of nestin expression 3 days post-ablation confirmed a significant
      two-fold increase in nestin expression (p<0.05). Double immunofluorescence
      labeling demonstrated that the majority of nestin expression occurred in
      astrocytes. We were unable to detect any colocalization with neuronal makers.
      However, BrdU-labeled cells, which were readily detected in the subventricular
      zone prior to injury, were readily detected in the perilesional area 3 days post
      ablation, concomitant with nestin in this area. Confocal microscopy detected
      several BrdU-positive cells expressing nestin. Taken together, the data support a
      potential role for nestin reexpression in brain repair.

PMID- 15145752
TI  - Expression of behavioral sensitization to the cocaine-like fungicide triadimefon
      is blocked by pretreatment with AMPA, NMDA and DA D1 receptor antagonists.
AB  - Triadimefon (TDF) is a triazole fungicide that blocks the reuptake of dopamine
      (DA), much like cocaine. A recent study in our laboratory found that intermittent
      injections of TDF led to robust locomotor sensitization in response to challenge
      TDF after a 2-week withdrawal period. The current study sought to determine
      whether the expression of TDF behavioral sensitization could be prevented by the
      DA D1-like receptor antagonist SCH 23390 (SCH), the DA D2-like receptor
      antagonist remoxipride (Rem), the competitive NMDA antagonist CPP, or the AMPA
      antagonist NBQX. Adult male C57/BL6 mice were injected with vehicle or 75 mg/kg
      TDF twice a week for 7 weeks, with locomotor activity measured periodically
      across the 14 doses. After a 2-week withdrawal period, mice were pretreated with
      SCH (0.015 mg/kg), Rem (0.3 mg/kg), CPP (2.5 mg/kg) or NBQX (10.0 mg/kg) followed
      30 min later by vehicle or 75 mg/kg TDF and tested for the expression of TDF
      sensitization. Intermittent administration of TDF led to the development and
      robust expression of behavioral sensitization in terms of vertical activity.
      Pretreatment with SCH, NBQX and CPP successfully blocked the expression of
      vertical sensitization to TDF, while Rem pretreatment did not. All four
      antagonists, however, attenuated the neurochemical changes normally associated
      with TDF sensitization as measured 8 h after the 2-week TDF challenge. This paper
      reveals that NMDA, AMPA and DA D1-like receptors are necessary for the behavioral
      expression of sensitization to the fungicide triadimefon.

PMID- 15145751
TI  - Estrogen attenuates nuclear factor-kappa B activation induced by transient
      cerebral ischemia.
AB  - The protective effects of estrogens have been widely reported in a number of
      animal and cell culture models, but the molecular mechanisms of this potent
      neuroprotective activity are not well understood. Both in vitro and in vivo
      studies indicate that in the central nervous system and peripheral tissues,
      estrogen treatment reduces cytokine production and inflammatory responses.
      Nuclear factor-kappa B (NFkappaB) plays an essential role in the regulation of
      post-ischemic inflammation, which is detrimental to recovery from an ischemic
      stroke. We investigated the role of NFkappaB in neuronal survival in rats that
      received transient middle cerebral artery (MCA) occlusion, and observed that this
      transient cerebral ischemia induced substantial apoptosis and inflammatory
      responses, including IkappaB phosphorylation, NF-kappaB activation and iNOS over
      expression. 17 beta-estradiol (E2) treatment produced strong protective effects
      by reducing infarct volume, neuronal apoptosis, and inflammatory responses. These
      findings provide evidence for a novel molecular and cellular interaction between
      the sex hormone and the immunoresponsive system. These studies also provide
      evidence that suppression of post-ischemic inflammation may play a critical role
      in estrogen-mediated neuroprotection.

PMID- 15145753
TI  - Acute high-fat diet paradigms link galanin to triglycerides and their transport
      and metabolism in muscle.
AB  - To compare the effects of acute exposure to dietary fat to those of chronic
      exposure, Sprague-Dawley rats were given a high-fat diet (50% fat) or moderate
      fat diet (25% fat) for 1 day, 2 h or 3 weeks. With measurements of various
      parameters, the high-fat diet for 21 days produced the expected changes of: (1) a
      significant increase in total caloric intake and dissected fat pad weights; (2) a
      rise in leptin and the metabolites, triglycerides (TG), non-esterified fatty
      acids and glucose; (3) an increase in muscle beta-hydroxyacyl-CoA dehydrogenase
      (HADH) and adipose lipoprotein lipase (aLPL) activity, along with a decrease in
      LPL activity in muscle (mLPL); and (4) elevated galanin (GAL) expression and
      peptide levels in the anterior region of the paraventricular nucleus (PVN), with
      no change in the arcuate nucleus. The acute 1-day or 2-h high-fat diet similarly
      increased circulating lipids, HADH activity and PVN GAL mRNA but stimulated
      rather than suppressed mLPL activity. These effects occurred in the absence of a
      change in total caloric intake, fat pad weights, and adipose-related measures,
      suggesting that they resulted more from the rise in dietary fat from 25% to 50%
      than from increased adiposity or hyperphagia. Moreover, PVN GAL mRNA in the
      different groups was consistently and positively correlated with the specific
      measures of TG levels and both HADH and mLPL activity, linking it to metabolic
      processes related to the transport and capacity for oxidation of TG in muscle,
      rather than adipose tissue.

PMID- 15145754
TI  - Mild hypothermia enhances the neuroprotective effects of FK506 and expands its
      therapeutic window following transient focal ischemia in rats.
AB  - FK506 (tacrolimus), an immunosuppressant, reportedly reduces ischemic brain
      injury following transient middle cerebral artery occlusion (MCAO) in rats. The
      authors previously reported that the therapeutic window of FK506 in this model is
      more than 1 h, but less than 2 h. The aim of the present study is to determine
      whether mild hypothermia (35 degrees C) enhances the neuroprotective effects of
      FK506 and expands its therapeutic window. Sprague-Dawley rats were subjected to 2
      h MCAO followed by 24 h reperfusion. Animals were randomly divided into four
      groups: (I) vehicle-treated normothermic group; (II) FK506-treated normothermic
      group; (III) vehicle-treated hypothermic group; (IV) FK506-treated hypothermic
      group. Animals received a single injection of FK506 (0.3 mg/kg) or vehicle
      intravenously at 2 h after ischemic induction. During ischemia, temporal muscle
      and rectal temperatures were maintained at 37 degrees C in the normothermic
      animals and at 35 degrees C in the hypothermic animals. Infarct volumes and
      neurological performance were evaluated at 24 h after reperfusion. The
      combination of FK506 and mild hypothermia significantly reduced infarct volume
      (cortex, -61%; striatum, -31%) and edema volume (cortex, -57%; striatum, -41%),
      while mild hypothermia or FK506 alone failed to improve ischemic brain damage.
      Furthermore, this combination also provided for the best functional outcome.
      These results demonstrate that the combination of FK506 and mild hypothermia
      significantly reduces ischemic brain damage following transient MCAO in rats, and
      expands the therapeutic window for FK506. This therapy may be a new approach for
      treatment of acute stroke.

PMID- 15145756
TI  - Esophagocardiac convergence onto thoracic spinal neurons: comparison of cervical
      and thoracic esophagus.
AB  - The aim of this study was to characterize thoracic spinal neurons receiving
      convergent inputs from the esophagus, heart and somatic receptive fields.
      Extracellular potentials of single T3-T4 spinal neurons were recorded in
      pentobarbital anesthetized male rats. Thoracic and cervical esophageal
      distensions (TED, CED) were produced by water inflation of a latex balloon. A
      catheter was placed in the pericardial sac to administer bradykinin or a mixture
      of algogenic chemicals. 96/311 (31%) neurons responded to both TED and
      intrapericardial chemicals (IC) and 48/177 (27%) neurons responded to both CED
      and IC. Long-lasting excitatory responses were more frequently encountered
      (P<0.05) in esophagocardiac spinal neurons responding to TED (T-ECSNs, 62/91)
      than in neurons responding to CED (C-ECSNs, 23/47). Ninety-one percent of T-ECSNs
      and 98% of C-ECSNs had somatic fields on chest, axilla and upper back areas.
      Esophagocardiac convergence on thoracic spinal neurons provided a spinal
      mechanism that might mediate viscerovisceral nociception and reflexes.

PMID- 15145755
TI  - Thalamic modulation of visceral nociceptive processing in adult rats with
      neonatal colon irritation.
AB  - Visceral pain originates from visceral organs in response to a noxious stimulus
      which, if prolonged, may lead to chronic changes in the neural network mediating
      visceral nociception. For instance, colon inflammation enhances the responses of
      neurons in the thalamus to colorectal distension (CRD), whereas lesion in the
      dorsal column (DC) reverses this neuronal sensitization, suggesting that the
      thalamus and the DC play major roles in chronic visceral pain. In this study, we
      used adult rats sensitized with neonatal painful colon irritation to reveal the
      contribution of the thalamus and the DC to neuronal hyperexcitability in a model
      of chronic visceral pain. We recorded the responses of lumbosacral neurons to CRD
      in control rats and in rats with colon irritation following stimulation or
      inactivation of the thalamus, and after DC lesion. Our results show that, first,
      neuronal responses to CRD decreased following thalamic stimulation in control
      rats, whereas, in rats with colon irritation, responses either decreased or
      increased; second, DC lesion attenuated or enhanced these effects in the
      positively or in the negatively modulated group of neurons, respectively; third,
      lidocaine injection in the thalamus reduced the responses to CRD in some of the
      neurons recorded in rats with colon irritation, but had no effect on those in
      control rats. Therefore, it is reasonable to speculate that plasticity in rats
      with colon irritation that may underlie chronic pain is sustained by feedback
      loops ascending in the DC and engaging the thalamus.

PMID- 15145757
TI  - Premature responding following bilateral stimulation of the rat subthalamic
      nucleus is amplitude and frequency dependent.
AB  - The subthalamic nucleus (STN), a key component of the basal ganglia circuitry,
      functions as an internal clock that regulates the correct sequence of movements
      in a motor response. The importance of the STN in motor function is evidenced by
      its involvement in Parkinson disease (PD). This nucleus has also been associated
      with the attentional and emotional aspects of motor behavior through its
      connections with the limbic and prefrontal areas of the brain. As lesions of the
      STN have been shown to increase premature responding in a serial reaction time
      task in rats, indicative of its involvement in cognitive performance, the present
      study aimed to investigate whether bilateral deep brain stimulation (DBS) of the
      STN, in non-lesioned rats, affects cognitive functions and whether these are
      dependent on certain stimulation parameters. Rats were trained in a choice
      reaction time task and implanted bilaterally with electrodes. Stimulation
      parameters (amplitude, frequency and pulse width) were varied during the test
      procedure, after which rats were sacrificed and the brains processed for
      histochemical staining. Results show no change in reaction times or motor times
      during stimulation. However, a linear decrease in premature responses was
      observed with decreasing amplitudes and at high frequencies only. These results
      are the first to demonstrate that bilateral STN HFS has a positive effect on
      cognition in freely moving rats. This latter result is in contrast to findings
      following lesions of the STN, and suggests that current strength and frequency of
      stimulation are parameters that are integral to the mediation of stimulation
      effects. Furthermore, the overall effects of DBS on neuronal cells cannot be
      classified simply as being "inhibitory" and evidently mediates its effects by
      more complex mechanisms than lesions of the same brain area.

PMID- 15145758
TI  - Cadmium inhibits GABA-activated ion currents by increasing intracellular calcium
      level in snail neurons.
AB  - Blocking of the GABA-activated chloride current by cadmium was investigated in
      identified nerve cells (RPeD1, RPaD1) of the pond snail (Lymnaea stagnalis L.),
      using a two-microelectrode voltage-clamp technique. Cd2+, at 50 microM
      extracellular concentration, inhibited GABA-activated chloride currents, both in
      normal and Ca2+-free solution. Intracellular injection of Ca2+ or the application
      of caffeine mimicked the inhibitory effect of Cd2+ on GABA-elicited currents.
      Cd2+-block was eliminated, or it was substantially decreased, when neurons were
      intracellularly loaded with EGTA, or when the Ca2+-release was blocked by
      ruthenium red. The blocking effect of Cd2+ was also eliminated by applying G
      protein inhibitors: pertussis toxin, suramin or GTP-gamma-S. Finally,
      intracellularly injected Cd2+ was ineffective at eliciting an inward current on
      GABA-activated currents, suggesting that the Cd2+-binding site resides
      extracellularly. These results suggest that cadmium inhibited GABA-activated
      chloride currents by increasing the intracellular Ca2+ level, by releasing it
      from intracellular stores and by interacting with a putative G-protein-coupled
      cell-surface "metal-receptor".

PMID- 15145760
TI  - Localization of components of the renin-angiotensin system in the suprachiasmatic
      nucleus of normotensive Sprague-Dawley rats: part B. angiotensin II (AT1)
      receptors, a light and electron microscopic study.
AB  - The dominant pacemaker of the mammalian circadian clock, located in the
      suprachiasmatic nucleus (SCN), is of special interest for many pharmacological,
      physiological and immunohistological studies on angiotensins and their receptors.
      Based on its role in the circadian modulation of blood pressure and vasopressin
      release, the distribution and function of the neuropeptide angiotensin II (ANG
      II) and its AT1-receptors (AT1) in the SCN became a target for several
      immunohistological studies. Though the distribution of ANG II and vasopressin in
      the SCN is well known at light microscopic level, detailed data concerning the
      AT1-receptor distribution in the SCN is missing. To confirm the mechanisms by
      which ANG II exerts its actions in the SCN, it is vital to understand how the
      brain renin-angiotensin system is organized at the cellular level, including the
      distribution of ANG II and the ANG II (AT1)-receptors as well as the protein
      receptor complex. The current paper presents a light- and electron microscopic
      study on AT1-receptor-immunolabeling in the suprachiasmatic nucleus of
      normotensive Sprague-Dawley rats.

PMID- 15145759
TI  - Localization of components of the renin-angiotensin system in the suprachiasmatic
      nucleus of normotensive Sprague-Dawley rats: part A. angiotensin I/II, a light
      and electron microscopic study.
AB  - The central pacemaker of the mammalian circadian clock, identified in the
      suprachiasmatic nucleus (SCN), is of special interest for many chronomedical
      studies on neuropeptides. Based on its role in the modulation of blood pressure
      and vasopressin release, the distribution and function of the neuropeptide
      angiotensin II (ANG II) in the SCN became a target for several immunohistological
      studies. At the light microscopic level, the distribution of ANG II in the SCN is
      well known, but detailed information about the localization of ANG II in the SCN
      at the ultrastructural level is missing. To gain further insight in the
      functional aspects of ANG II in the SCN, we investigated on the subcellular
      localization of the neuropeptide ANG II and its precursor ANG I in the SCN. The
      current report presents a light and electron microscopic study on ANG I/II
      immunoreactivity in the suprachiasmatic nucleus of normotensive Sprague-Dawley
      rats.

PMID- 15145761
TI  - Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405
      on vigilance, behavior and spike-wave discharges in a genetic rat model of
      absence epilepsy.
AB  - The present study was conducted to investigate the effects of two noncompetitive
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the
      generation of spike-wave discharges (SWD) parallel with the vigilance and
      behavioral changes in the genetic absence epilepsy model of WAG/Rij rats.
      Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl
      7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the
      prototypic compound of the 2,3-benzodiazepine family, caused a fast dose
      dependent increase in the number and cumulative duration of SWD. These changes
      were accompanied by dose-dependent increase in duration of light slow wave sleep
      (SWS1) and passive awake, vigilance states associated with the presence of SWD.
      In addition a short, transient behavioral activation occurred that was followed
      by strong ataxia and immobility, decrease of active wakefulness and increase in
      deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro
      7H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg,
      i.p.) failed to affect any measure of SWD and vigilance. When used as a
      pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of
      the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and
      average time of paroxysms. In conclusion, AMPA receptors play moderate role in
      regulation of epileptic activity, and some of these effects are connected to
      their effects on vigilance in this model.

PMID- 15145762
TI  - Polyamines reduces lipid peroxidation induced by different pro-oxidant agents.
AB  - Polyamines, among other functions, are considered to act as a free radical
      scavenger and antioxidant. The quinolinic acid (QA), sodium nitroprusside (SNP)
      and iron (Fe+2) stimulate production of free radicals and lipid peroxidation. In
      the present study, we investigated the free radical and/or aldehyde scavenger
      effects of polyamines spermine and spermidine on thiobarbituric acid reactive
      species (TBARS) production induced by QA, SNP, Fe+2/EDTA system and free Fe2+ in
      rat brain. Spermine and spermidine inhibited QA-induced TBARS production; however
      spermine was a better antioxidant than spermidine. Spermine also inhibited SNP-,
      Fe+2/EDTA- and free Fe2+-induced TBARS production, but had a modest effect.
      Spermidine, in turn, also discretely inhibited SNP-, Fe+2/EDTA- and free Fe2+
      induced TBARS production. In the presence of MK-801, QA-induced TBARS production
      was considerably more inhibited by polyamines. In addition, arcaine does not
      affect the reducer effect of polyamines. The present findings suggest that the
      observed effects of polyamines are not related to the activation of NMDA receptor
      but with their antioxidant and free radical scavenger properties.

PMID- 15145763
TI  - Diazoxide and dimethyl sulphoxide prevent cerebral hypoperfusion-related learning
      dysfunction and brain damage after carotid artery occlusion.
AB  - Chronic cerebral hypoperfusion, a mild ischemic condition is associated with
      advancing age and severity of dementia; however, no unanimous therapy has been
      established to alleviate related neurological symptoms. We imposed a permanent,
      bilateral occlusion of the common carotid arteries of rats (n=18) to create
      cerebral hypoperfusion. A mitochondrial ATP-sensitive K+ channel opener diazoxide
      (DZ, 5 mg/kg) or its solvent dimethyl sulphoxide (DMSO) were administered i.p.
      (0.25 ml) on five consecutive days after surgery. Sham-operated animals (n=18)
      served as control for the surgery, while nontreated rats were used as control for
      the treatments. Three months after the onset of cerebral hypoperfusion, the rats
      were tested in a hippocampus-related learning paradigm, the Morris water maze.
      Subsequently, the animals were sacrificed and neurons, astrocytes and microglia
      were labeled with immunocytochemistry in the dorsal hippocampus. DMSO and
      diazoxide dissolved in DMSO restored cerebral hypoperfusion-related learning
      dysfunction and prevented cyclooxygenase-2-positive neuron loss in the dentate
      gyrus. Cerebral hypoperfusion led to reduced astrocyte proliferation, which was
      not clearly affected by the treatment. Microglia activation was considerably
      enhanced by cerebral hypoperfusion, which was completely prevented by diazoxide
      dissolved in DMSO, but not by DMSO alone. We conclude that diazoxide can moderate
      ischemia-related neuroinflammation by suppressing microglial activation.
      Furthermore, we suggest that DMSO is a neuroprotective chemical in ischemic
      conditions, and it must be considerately used as a solvent for water-insoluble
      compounds in experimental animal models.

PMID- 15145764
TI  - Effect of mediodorsal thalamic nucleus lesion on contextual fear conditioning in
      rats.
AB  - Much evidence from animal and clinical studies has shown that the mediodorsal
      nucleus of the thalamus (MD) is related to various types of memory, such as
      visual recognition, object-reward association, spatial working, and reference
      memory; however, few studies have investigated its role in emotion-related
      learning and memory processes. This study compared the effect of pre- and
      posttraining bilateral lesions of the mediodorsal thalamic nucleus with those of
      the amygdala on contextual conditioned fear. Both pre- and posttraining amygdala
      lesions almost eliminated conditioned freezing, and significantly blocked
      postshock freezing when behavioral tests were performed immediately after
      footshocks, reconfirming previous studies that the amygdala is implicated in the
      learning of Pavlovian conditioning. Both pre- and posttraining lesions of the
      mediodorsal nucleus of the thalamus significantly attenuated conditioned freezing
      but had no effect on postshock freezing. In contrast to lesions of the amygdala,
      those of the mediodorsal thalamic nucleus failed to alter the increased
      defecation induced by conditioned fear stress. Our results suggest that the
      mediodorsal nucleus of the thalamus has an important role in acquisition,
      consolidation or retrieval in Pavlovian contextual fear conditioning. Possible
      neural circuits, incorporating the amygdala, MD, and hippocampus, and the
      functional similarity of the MD and hippocampus in contextual fear conditioning,
      are also discussed.

PMID- 15145765
TI  - Neurons in and near insular cortex are responsive to muscular contraction and
      have sympathetic and/or cardiac-related discharge.
AB  - Insular cortex (IC) is recognized as a potential site for "central command" of
      cardiorespiratory responses during exercise. Muscular contraction (MC) decreased
      the discharge rate of most IC neurons. Activity of most contraction sensitive
      neurons was either not altered by elevating blood pressure or showed a response
      converse to that of MC. IC may thus have a role in central command but the area
      is clearly modulated by MC.

PMID- 15145766
TI  - Caffeinol confers cortical but not subcortical neuroprotection after transient
      focal cerebral ischemia in rats.
AB  - The combination of low-dose ethanol and caffeine (caffeinol) protects cortical
      areas of the brain from damage produced by distal focal ischemia in rats. There
      are no data, however, as to whether caffeinol influences injury in subcortical
      brain regions. Rats were anesthetized with halothane and subjected to 2 h of MCAo
      by poly-l-lysine-coated intraluminal suture. Caffeinol [a combination of ethanol,
      0.33 g/kg, and caffeine, 10 mg/kg (n=5)] or vehicle (0.9% NaCl; n=7) was
      administered by i.v. infusion over a 2.5-h period beginning 15 min after
      reperfusion. Neurological status was evaluated daily, and histopathology was
      quantified at 3 days. Caffeinol therapy significantly improved the neurological
      score, reduced the total infarct volume (by 52%) and cortical infarct areas at
      multiple coronal levels, but subcortical infarction and brain swelling were not
      affected.

PMID- 15145767
TI  - Polyethylenimine-mediated NGF gene delivery protects transected septal
      cholinergic neurons.
AB  - Polyethylenimine (PEI) is an effective vehicle for in vivo gene delivery in many
      tissues including brain. PEI mediates transgene expression in brain neurons and
      glia. To investigate whether PEI-mediated nerve growth factor (NGF) gene transfer
      protected axotomized septal cholinergic neurons, we injected linear PEI (in vivo
      jetPEI, Qbiogene) complexed with a plasmid encoding for mouse NGF (PEI/pNGF-W)
      into the rat septum. PEI complexed with a plasmid encoding for green fluorescent
      protein (PEI/pGFP) was used as the control. PEI-mediated gene expression was
      predominantly neuronal. Fimbria-fornix transections (FFTs), conducted 1 day after
      rats were injected with control vector, resulted in a 70% loss of septal
      cholinergic neurons. In contrast, PEI/pNGF-W injection prior to FFTs attenuated
      the loss of septal cholinergic neurons. This is the first study, to our
      knowledge, that shows the neuroprotective effects induced by PEI-mediated trophic
      factor gene transfer in brain.

PMID- 15145768
TI  - Blockade of supraspinal 5-HT1A receptors potentiates the inhibitory effect of
      venlafaxine on wind-up activity in mononeuropathic rats.
AB  - In mononeuropathic rats submitted to a C-fiber reflex responses paradigm,
      repeated administration (five successive injections every half-life) of 10 mg/kg,
      s.c. of venlafaxine, but not of 2.5 mg/kg, s.c., a mixed monoamine reuptake
      inhibitor with preferential inhibitory activity in 5-HT reuptake, induced a
      progressive reduction of spinal wind-up. Repeated co-administration of the
      selective 5-HT1A receptor antagonist WAY 100,635 i.c.v. (50 microg/injection)
      significantly increased the effect of venlafaxine s.c., indicating that
      venlafaxine-induced inhibition of spinal wind-up in mononeuropathic rats is
      potentiated by blockade of central 5-HT1A receptors.

PMID- 15145769
TI  - The effects of nitric oxide on striatal serotoninergic transmission involve
      multiple targets: an in vivo microdialysis study in the awake rat.
AB  - The role of endogenous nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-induced
      modulation of serotonin (5-HT) release in the striatum of freely moving rats has
      been studied using microdialysis technique. NMDA-induced increase in 5-HT release
      was significantly inhibited by selective nitric oxide synthase (nNOS) inhibitor S
      methylthiocitrulline (S-Me-TC), ONOO- scavenger L-cysteine (L-cys), and guanylate
      cyclase (GC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). These
      data suggest that modulation of 5-HT levels is linked to the formation of NO
      produced by NMDA receptor activation and that endogenously produced NO increases
      5-HT concentrations both by stimulating formation of 3'-5'-cyclic monophosphate
      (cGMP) and conversion of ONOO-.

PMID- 15145771
TI  - Ultrastructural cytochemical analyses of nuclear functional architecture.
AB  - For many years, ultrastructural cytochemistry has been a major tool for
      investigating the relationships between the structure and the functions of the
      cell nucleus. This article shortly reviews the contributions of transmission
      electron microscopy to the in situ studies of intranuclear distribution of
      chromatin domains and of essential nuclear functions, such as DNA replication,
      transcription and pre-mRNA processing. It attempts to analyse the role of
      different nuclear structural domains in nuclear functions, as well as further
      directions in this important field of research.

PMID- 15145772
TI  - Three dimensional analysis of histone methylation patterns in normal and tumor
      cell nuclei.
AB  - Histone modifications represent an important epigenetic mechanism for the
      organization of higher order chromatin structure and gene regulation. Methylation
      of position-specific lysine residues in the histone H3 and H4 amino termini has
      linked with the formation of constitutive and facultative heterochromatin as well
      as with specifically repressed single gene loci. Using an antibody, directed
      against dimethylated lysine 9 of histone H3 and several other lysine methylation
      sites, we visualized the nuclear distribution pattern of chromatin flagged by
      these methylated lysines in 3D preserved nuclei of normal and malignant cell
      types. Optical confocal serial sections were used for a quantitative evaluation.
      We demonstrate distinct differences of these histone methylation patterns among
      nuclei of different cell types after exit of the cell cycle. Changes in the
      pattern formation were also observed during the cell cycle. Our data suggest an
      important role of methylated histones in the reestablishment of higher order
      chromatin arrangements during telophase/early G1. Cell type specific histone
      methylation patterns are possibly casually involved in the formation of cell type
      specific heterochromatin compartments, composed of (peri)centromeric regions and
      chromosomal subregions from neighboring chromosomes territories, which contain
      silent genes.

PMID- 15145773
TI  - Common fragile genes.
AB  - Common chromosome fragile sites show susceptibility to DNA damage, leading to
      alterations that contribute to cancer development. The cloning and
      characterization of fragile sites have demonstrated that fragile sites are
      associated with genes that relate to tumorigenesis. Identification of the basis
      of instability at fragile sites and the related genes provides an entree to
      understanding of important aspects of chromosomal instability, a prominent
      feature of neoplastic genomes. FHIT/FRA3B and WWOX/FRA16D, the most sensitive
      common fragile genes in the human genome, function as tumor suppressor genes. The
      common features of these two common fragile genes are summarized, and suggest
      clues to understanding the relation between genomic instability and tumor
      biology.

PMID- 15145774
TI  - G0-G1 cell cycle phase transition as revealed by fluorescence resonance energy
      transfer: analysis of human fibroblast chromatin.
AB  - In the present study, microspectrofluorometry and digital imaging procedures were
      used to investigate by fluorescence Resonance Energy Transfer (FRET) analysis the
      changes of chromatin organization during the transition from G0 quiescent stat to
      G1 phase. G0 transition is a key event in cell cycle progress depending on the
      activation of specific genes and the concomitant silencing of others, which both
      entail spatial chromatin rearrangement. Normal human fibroblasts arrested in G0
      phase by culture in low-serum containing medium and stimulated to re-enter G1 by
      serum addition were used as cell model. To investigate the occurrence and timing
      of these supramolecular chromatin changes, we estimated the relative FRET
      efficiency in single cells after double-helical DNA. Hoechst 33258 amd propidium
      iodide were used as a donor-acceptor dye pair since they exhibit particularly
      favourable spectral characteristics, that allow the calculation procedure to be
      semplified. The results of FRET analysis were compared to those of the
      immunocytochemical labelling of two nuclear proteins (i.e., Ki-67 and statin)
      whose expression is an established marker of potentially proliferating G1 cells
      or resting G0 cells, respectively. FRET efficiency was lower in G0 than G1
      fibroblasts: this is likely due to higher chromatin packaging in quiescent cells
      which especially hinders the interaction with the donor molecules less
      favourable, in terms of relative distance and spatial orientation. FRET
      efficiency significantly increased shortly (1h) after serum stimulation of
      quiescent fibroblasts, thus indicating that chromatin is rearranged in parallel
      with activation of cycle-related gene; it is worth noting that these signs
      largely preceded the occurrence of immunopositivity for Ki-67, which was
      detectable only 24h after serum stimulation. FRET-based analyses which already
      proved to be suitable for studying the overall chromatin organization in
      differentiated cells, may now be envisaged as a powerful tool for detecting, in
      single cells, more subtle changes linked to the activation of early cycle-related
      genes.

PMID- 15145775
TI  - Z-DNA, a new in situ marker for transcription.
AB  - Z-DNA forms transiently behind the active RNA polymerases, because of the
      mechanical torsional stress produced during transcription. In this paper, we
      explore the possibility that the distribution of Z-DNA stretches signals the
      sites related to nuclear transcription. To localize transcription, the in situ
      assay for active RNA polymerases, that allows the elongation of the already
      initiated transcripts but no initiation of new ones (run-on experiments), was
      carried out in isolated nuclei of Allium cepa L. root meristems. Both nucleolar
      and non-nucleolar sites appeared labelled. Nucleoli were most active in
      transcription than the multiple non-nucleolar foci altogether. In situ
      immunodetection of Z-DNA provided images that were comparable to those obtained
      after the run-on assay, with one exception: while Z-DNA and transcription sites
      were scattered throughout the whole nucleus, Z-DNA also accumulated in the
      nuclear periphery, where no transcription foci were detected in run-on assays.
      The peripheral Z-conformation signals might correspond to dsRNA segments present
      in the pre-mRNA in the process of their export to cytoplasm. The Z-containing
      structures nearly disappeared when non-nucleolar RNA polymerase II-dependent
      transcription had been previously abolished by the adenosine analogue DRB (5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole). This inhibition selectively
      decreased the amount of all nucleoplasmic Z structures. On the other hand, the
      inhibition of the nucleolar RNA polymerase I by cordycepin (3'-deoxyadenosine)
      prevented the presence of Z-DNA in nucleoli. We propose to use the in situ
      immunodetection of Z-DNA as a marker of the transcription level in both nucleolus
      and non-peripheral nucleoplasmic regions of nuclei. Co-detection of Z-DNA and of
      intermediate filament (IF) proteins, the major components of the nuclear matrix,
      was also carried out. The IFA antibody recognizes a conserved epitope essential
      for dimerization of the multiple IF proteins. They co-localized with most
      nucleolar Z-DNA, but not with the nucleoplasmic ones. In the nuclear periphery,
      the Z-positive signals were adjacent to the IF proteins constituting the lamina,
      though both signals did not often co-localize.

PMID- 15145776
TI  - The molecular cytology of gene expression: fluorescent RNA as both a stain and
      tracer in vivo.
AB  - For more than 60 years, RNA has been detectable in fixed cells and tissues by
      relatively specific staining methods. More recently, it has become possible to
      study RNA in unfixed, live cells. This review article describes how the
      intracellular dynamics and localization of RNA in vivo can be studied by
      microinjection of fluorescent RNA into cells- an approach we have termed
      Fluorescent RNA Cytochemistry. Depending on the particular RNA species under
      investigation, Fluorescent RNA Cytochemistry can operate as a "stain" to reveal
      intracellular sites at which a given RNA resides, or as a "tracer" to allow
      movements of a dynamically translocating RNA to be followed in the living cell.
      Several examples of Fluorescent RNA Cytochemistry are presented, collectively
      illustrating the range of applicability this approach offers in the toolbox of
      gene expression, studied as in vivo cell biology.

PMID- 15145778
TI  - Nuclear production and metabolism of diacylglycerol.
AB  - The story of nuclear diacyglycerol is proving to be a complex one. Sub-pools of
      nuclear diglyceride that differ in their metabolism, nuclear localization and
      temporal regulation have been identified, suggesting potentially diverse
      signaling functions. One of the great remaining challenges is to assign
      functional roles to these diverse populations. In the last twenty years great
      strides have been made toward understanding the character and composition of
      nuclear DAG. Determining the functions of this nuclear lipid should make the next
      twenty years interesting indeed.

PMID- 15145777
TI  - Nuclear microenvironments: an architectural platform for the convergence and
      integration of transcriptional regulatory signals.
AB  - Functional interrelationships between the intranuclear organization of nucleic
      acids and regulatory proteins are obligatory for fidelity of transcriptional
      activation and repression. In this article, using the Runx/AML/Cbfa transcription
      factors as a paradigm for linkage between nuclear structure and gene expression
      we present an overview of growing insight into the dynamic organization and
      assembly of regulatory machinery for gene expression at microenvironments within
      the nucleus. We address contributions of nuclear microenvironments to the
      convergence and integration of regulatory signals that mediate transcription by
      supporting the combinatorial assembly of regulatory complexes.

PMID- 15145779
TI  - New frontiers of inositide-specific phospholipase C in nuclear signalling.
AB  - Strong evidence has been obtained during the last 16 years suggesting that
      phosphoinositides, which are involved in the regulation of a large variety of
      cellular processes in the cytoplasm and in the plasma membrane, are present
      within the nucleus. A number of advances has resulted in the discovery that
      nuclear phosphoinositides and their metabolizing enzymes are deeply involved in
      cell growth and differentiation. Remarkably, the nuclear inositide metabolism is
      regulated independently from that present elsewhere in the cell. Even though
      nuclear inositol lipids generate second messengers such as diacyglycerol and
      inositol 1,4,5-trisphosphate, it is becoming increasingly clear that in the
      nucleus polyphosphoinositides may act by themselves to influence functions such
      as pre-mRNA splicing and chromatin structure. This review aims at highlighting
      the most significant and up-dated findings about inositol lipid metabolism in the
      nucleus.

PMID- 15145780
TI  - Nuclear protein kinase C isoforms and apoptosis.
AB  - The process of apoptosis is regulated at multiple levels through phosphorylation
      by several different protein kinases. The protein kinase C (PKC) family of
      isozymes have been shown to exert both inhibitory and stimulatory influences on
      apoptosis. During the apoptotic process phosphorylative events are known to occur
      also at the nuclear level. Evidence suggests that PKC isoforms play a key role in
      some steps that lead to nuclear disassembly during the execution phase of
      apoptosis. This review highlights the recent progress made in determining the
      roles played by individual PKC nuclear isoforms in the control of apoptosis.

PMID- 15145783
TI  - The effects of continuing medical education credits on physician response rates
      to a mailed questionnaire.
AB  - This study investigated whether the opportunity to obtain Continuing Medical
      Education (CME) credit together with a five-dollar bill increased response rates
      and questionnaire completion rates in a physician survey involving mailed
      questionnaires. One thousand, three hundred and fourteen cardiologists, family
      practitioners, general internists (non-surgeons) and 264 vascular surgeons
      randomly identified from the American Medical Association database participated.
      After two, of up to four, questionnaire mailings, the opportunity to obtain CME
      credit and a five-dollar bill were included with questionnaire mailings. Among
      non-surgeons, 26.5% responded to pre-incentive mailings and 30.2% of those
      initially unresponsive replied after the interventions. Among surgeons, 39%
      responded to pre-incentive mailings and 32.7% of those initially unresponsive
      replied after the interventions. In conclusion, the opportunity to receive CME
      credit combined with a small monetary incentive is an effective motivation for
      physicians participating in a study involving mailed questionnaires.

PMID- 15145782
TI  - Smoking among university students in Canada and South Korea: linking diffusion
      theory with consumer susceptibility to interpersonal influence.
AB  - This research examines the relationship between consumer susceptibility to
      interpersonal influence (CSII) and smoking diffusion patterns in Canada and South
      Korea. It is hypothesized that individuals with higher susceptibility to
      interpersonal influence are more likely to follow the dominant trend with regard
      to smoking behavior. Among South Korean females, smoking prevalence has been
      increasing and, in line with this trend, smokers were found to have a higher
      susceptibility to interpersonal influence than non-smokers. Among Canadians and
      among South Korean males, smoking has been in decline and, in line with this
      trend, non-smokers were found to have a higher susceptibility to interpersonal
      influence than smokers. Implications for social marketers and health
      professionals are discussed.

PMID- 15145784
TI  - To treat or not to treat: evidence for "treatment bias" when consumers evaluate
      physicians.
AB  - Previous research has generally ignored whether consumers exhibit a "treatment
      bias" and have more favorable opinions of physicians who provide more treatment
      even if the benefits of more treatment are equivocal. This research
      experimentally manipulates three variables, (1) treatment choice (more treatment
      versus less treatment), (2) interpersonal treatment (patient involvement with
      treatment decisions), and (3) health outcomes, and examines their influence on
      respondent's inferences about the physician's ability, concern for patient
      welfare, quality of care, and accountability for patient death. Results clearly
      showed evidence of a treatment bias. Consumers made more favorable inferences
      about the physician in the more treatment condition even though both physicians
      acknowledged that the less treatment option was recommended for the patient.
      Results also showed that consumers' inferences about the physician were more
      favorable in the better health outcomes condition. There was no influence of
      patient involvement on consumers' inferences about the physician.

PMID- 15145785
TI  - Internal marketing, nurse loyalty and relationship marketing: an exploratory
      study of German nurses.
AB  - Nurse loyalty and retention are critical issues facing the healthcare industry. A
      lack of continuity in the nursing staff compromises the quality of the care,
      results in significant costs, and leads to patient concerns about the viability
      of the healthcare facility. Conversely, a motivated and committed nursing staff
      creates a solid foundation for implementing initiatives for the improvement of
      healthcare quality. This article employs the "Relationship Marketing Paradigm" as
      a framework to understand and enhance nurse loyalty through internal marketing
      efforts. The results indicate that financial, social and structural bonds have
      significant, albeit different, impacts on nurse loyalty. Managerial implications
      and future research directions are discussed.

PMID- 15145787
TI  - Leptin augments alveolar macrophage leukotriene synthesis by increasing
      phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein
      expression.
AB  - Leptin is a hormone secreted by adipocytes in correlation with total body fat
      mass. In addition to regulating energy homeostasis, leptin modulates immune
      functions such as macrophage phagocytosis and cytokine synthesis. Previously, we
      reported defective leukotriene synthesis in macrophages from leptin-deficient
      mice that could be restored with exogenous leptin. In the present study, we
      utilized macrophages from normal rodents to explore the mechanism by which leptin
      could enhance cellular leukotriene synthesis. Leptin pretreatment of either rat
      alveolar or murine peritoneal macrophages for 16 h dose dependently increased the
      synthesis of leukotriene B4 and cysteinyl leukotrienes in response to calcium
      ionophore or the particulate zymosan. Leptin also enhanced calcium ionophore
      stimulated release of free arachidonic acid. Calcium-dependent and -independent
      arachidonoyl-selective phospholipase activities in macrophage lysates were
      likewise increased following leptin treatment. Immunoblot analysis of leptin
      treated cells revealed that group IVC iPLA2 (cPLA2gamma) protein expression
      increased approximately 80%. These data demonstrate for the first time that
      phospholipase A2 activity and cPLA2gamma protein levels in alveolar macrophages
      represent targets for upregulation by leptin and provide previously unrecognized
      mechanisms by which this hormone can promote inflammatory responses.

PMID- 15145786
TI  - Mechanical ventilation with moderate tidal volumes synergistically increases lung
      cytokine response to systemic endotoxin.
AB  - Previous animal studies have identified a role for activation of innate immunity
      in the pathogenesis of ventilator-associated lung injury. These studies have used
      large tidal volume ventilation to study the effect of alveolar overdistension on
      induction of inflammatory pathways. We hypothesized an alternative mechanism for
      the pathogenesis of lung injury in which moderate tidal volume ventilation does
      not independently cause clinical inflammation but rather interacts with innate
      immune activation by bacterial products, resulting in an enhanced inflammatory
      response. We measured cytokine expression and lung injury in normal and
      lipopolysaccharide (LPS)-treated anesthetized rabbits randomized to either
      spontaneous respiration or mechanical ventilation. Outcome parameters were
      analyzed by two-way factorial analysis of variance to identify synergism between
      ventilation and systemic LPS. Mechanical ventilation alone resulted in minimal
      cytokine expression in the lung but did enhance LPS-induced expression of tumor
      necrosis factor-alpha, the CXC chemokines interleukin-8 and growth-related
      protein-alpha, and the CC chemokine monocyte chemoattractant protein-1. Increased
      mRNA expression and activation of the transcription factors nuclear factor-kappaB
      and activator protein-1 accompanied the cytokine responses. We conclude that
      moderate volume ventilation strategies augment the innate immune response to
      bacterial products in the lung and may play a role in the development of acute
      lung injury in patients with sepsis.

PMID- 15145788
TI  - Dynamic interaction between airway epithelial cells and Staphylococcus aureus.
AB  - Staphylococcus aureus is a major cause of pulmonary infection, particularly in
      cystic fibrosis (CF) patients. However, few aspects of the interplay between S.
      aureus and host airway epithelial cells have been investigated thus far. We
      investigated by videomicroscopy the time- and bacterial concentration-dependent
      (10(4), 10(6), and 10(8) CFU/ml) effect of S. aureus on adherence,
      internalization, and the associated damage of the airway epithelial cells. The
      balance between the secretion by S. aureus of the alpha-toxin virulence factor
      and by the airway cells of the antibacterial secretory leukoproteinase inhibitor
      (SLPI) was also analyzed. After 1 h of interaction, whatever the initial
      bacterial concentration, a low percentage of S. aureus (<8%) adhered to airway
      cells, and no airway epithelial cell damage was observed. In contrast, after 24 h
      of incubation, more bacteria adhered to airway epithelial cells, internalized
      bacteria were observed, and a bacterial concentration-dependent effect on airway
      cell damage was observed. At 24 h, most airway cells incubated with bacteria at
      10(8) CFU/ml exhibited a necrotic phenotype. The necrosis was preceded by a
      transient apoptotic process. In parallel, we observed a time- and bacterial
      concentration-dependent decrease in SLPI and increase in alpha-toxin expression.
      These results suggest that airway cells can defend against S. aureus in the early
      stages of infection. However, in later phases, there is a marked imbalance
      between the bactericidal capacity of host cells and bacterial virulence. These
      findings reinforce the potential importance of S. aureus in the pathogenicity of
      airway infections, including those observed early in CF patients.

PMID- 15145789
TI  - Phenylpropanoids, phenylalanine ammonia lyase and peroxidases in elicitor
      challenged cassava (Manihot esculenta) suspension cells and leaves.
AB  - BACKGROUND AND AIMS: Control of diseases in the key tropical staple, cassava, is
      dependent on resistant genotypes, but the innate mechanisms are unknown. The aim
      was to study phenylpropanoids and associated enzymes as possible defence
      components. METHODS: Phenylalanine ammonia-lyase (PAL), phenylpropanoids and
      peroxidases (POD) were investigated in elicited cassava suspension cells and
      leaves. Yeast elicitor was the most effective of several microbial and endogenous
      elicitors. Fungitoxicity was determined against the cassava pathogens Fusarium
      solani, F. oxysporum and the saprotroph Trichoderma harzianum. KEY RESULTS: A
      single and rapid (> or =2-3 min) oxidative burst, measured as hydrogen peroxide,
      occurred in elicited cells. PAL activity was induced maximally at 15 h and was
      preceded by PAL mRNA accumulation, which peaked at 9 h. Symplasmic POD activity
      increased four-fold in cells, 48 h post-elicitation. POD isoforms (2-7 isoforms,
      pI 3.1-8.8) were detected in elicited and unelicited cells, extracellular medium
      and leaves but two extracellular isoforms were enhanced post-elicitation. Also
      expression of a cassava peroxidase gene MecPOD1 increased in elicited cells. Only
      anionic forms oxidized scopoletin, with highest activity by isoform pI 3.6,
      present in all samples. Unidentified phenolics and possibly scopolin increased
      post-elicitation, but there was no enhancement of scopoletin, rutin or kaempferol
      3-O-rutinoside concentration. Fungal germ tube elongation was inhibited more than
      germination by esculetin, ferulic acid, quercetin and scopoletin. T. harzianum
      was generally more sensitive than the pathogens and was inhibited by > or =50
      microg mL(-1) of ferulic acid and quercetin and > or =10 microg mL(-1) of
      scopoletin. CONCLUSIONS: Phenolic levels in cells were not enhanced and were,
      theoretically, too low to be inhibitory. However, in combination and when
      oxidized they may contribute to defence, because oxidation of esculetin and
      scopoletin by peroxidase and of esculetin by tyrosinase enhanced their
      fungitoxicity up to 20-fold.

PMID- 15145791
TI  - Modelling applicability of fractal analysis to efficiency of soil exploration by
      roots.
AB  - BACKGROUND AND AIMS: Fractal analysis allows calculation of fractal dimension,
      fractal abundance and lacunarity. Fractal analysis of plant roots has revealed
      correlations of fractal dimension with age, topology or genotypic variation,
      while fractal abundance has been associated with root length. Lacunarity is
      associated with heterogeneity of distribution, and has yet to be utilized in
      analysis of roots. In this study, fractal analysis was applied to the study of
      root architecture and acquisition of diffusion-limited nutrients. The hypothesis
      that soil depletion and root competition are more closely correlated with a
      combination of fractal parameters than by any one alone was tested. MODEL: The
      geometric simulation model SimRoot was used to dynamically model roots of various
      architectures growing for up to 16 d in three soil types with contrasting
      nutrient mobility. Fractal parameters were calculated for whole roots,
      projections of roots and vertical slices of roots taken at 0, 2.5 and 5 cm from
      the root origin. Nutrient depletion volumes, competition volumes, and relative
      competition were regressed against fractal parameters and root length. KEY
      RESULTS: Root length was correlated with depletion volume, competition volume and
      relative competition at all times. In analysis of three-dimensional, projected
      roots and 0 cm slices, log(fractal abundance) was highly correlated with
      log(depletion volume) when times were pooled. Other than this, multiple
      regression yielded better correlations than regression with single fractal
      parameters. Correlations decreased with age of roots and distance of vertical
      slices from the root origin. Field data were also examined to see if fractal
      dimension, fractal abundance and lacunarity can be used to distinguish common
      bean genotypes in field situations. There were significant differences in fractal
      dimension and fractal abundance, but not in lacunarity. CONCLUSIONS: These
      results suggest that applying fractal analysis to research of soil exploration by
      root systems should include fractal abundance, and possibly lacunarity, along
      with fractal dimension.

PMID- 15145790
TI  - Growth rings, growth ring formation and age determination in the mangrove
      Rhizophora mucronata.
AB  - BACKGROUND AND AIMS: The mangrove Rhizophora mucronata has previously been
      reported to lack annual growth rings, thus barring it from dendrochronological
      studies. In this study the reported absence of the growth rings was reconsidered
      and the periodic nature of light and dark brown layers visible on polished stem
      discs investigated. In addition, the formation of these layers in relation to
      prevailing environmental conditions, as well as their potential for age
      determination of the trees, was studied. METHODS: Trees of known age were
      collected and a 2.5-year cambial marking experiment was conducted to determine
      the periodic nature of the visible growth layers. KEY RESULTS: Annual indistinct
      growth rings were detected in R. mucronata and are defined by a low vessel
      density earlywood and a high vessel density latewood. The formation of these
      growth rings and their periodic nature was independent from site-specific
      environmental conditions in two forests along the Kenyan coast. However, the
      periodic nature of the rings was seriously affected by slow growth rates,
      allowing accurate age determination only in trees with radial growth rates above
      0.5 mm year(-1). The onset of the formation of the low vessel density wood
      coincided with the onset of the long rainy season (April-May) and continues until
      the end of the short rainy season (November). The high vessel density wood is
      formed during the dry season (December-March). Age determination of the largest
      trees collected in the two studied forests revealed the relatively young age of
      these trees (+/-100 years). CONCLUSIONS: This study reports, for the first time,
      the presence of annual growth rings in the mangrove R. mucronata, which offers
      further potential for dendrochronological and silvicultural applications.

PMID- 15145793
TI  - Phenological responses to temperature of an annual and a perennial Lesquerella
      species.
AB  - BACKGROUND AND AIMS: The annual Lesquerella fendleri, native to the south-western
      desert of United States and Mexico, and the perennial L. mendocina, native to
      Argentina, may have potential as new crops for cold-arid environments. The
      introduction of a new crop requires an understanding of environmental influences
      on growth and development, particularly temperature, which has been recognized as
      the main factor affecting the rate of development in crops. The objective of this
      study was to examine differences in the phenology of L. fendleri and L. mendocina
      and in the response to temperature in both vegetative and reproductive phases.
      METHODS: Plants of each species were grown at a range of constant temperatures
      under controlled conditions and developmental responses were analysed and
      quantified. KEY RESULTS: The rate of development of L. fendleri increased
      linearly with temperature in the phase from emergence (EM) to floral bud
      appearance (FBA) over the range 9-20 degrees C, and for the phase from FBA to
      first flower open (FL) over the range 9-24 degrees C. In contrast, the rate of
      development of L. mendocina was insensitive to temperature during the phase EM to
      FBA. In the phase FBA to FL, L. mendocina had a lower sensitivity to temperature
      than L. fendleri. In addition, L. fendleri exhibited a quantitative response to
      supra-optimal temperatures (reducing rate of development with further increases
      in temperature) whereas L. mendocina showed a qualitative response, with
      development ceasing to progress at temperatures above the optimum. CONCLUSIONS:
      This differential behaviour at high temperatures could explain the biennial habit
      found for L. mendocina sown during late spring under field conditions, whereas it
      behaves as an annual when sown in autumn-winter. The possibility is discussed of
      using this information for establishing the coincidence of critical stages with
      environmental conditions that can limit potential and actual yield through
      agronomic practices.

PMID- 15145792
TI  - ISSR variation in the endemic and endangered plant Cycas guizhouensis
      (Cycadaceae).
AB  - BACKGROUND AND AIMS: Cycas guizhouensis (Cycadaceae) is a rare and endangered
      species endemic to the southwest of China. An investigation was undertaken into
      the genetic variation of wild populations. METHODS: ISSR markers were used to
      determine the genetic variation within and between 12 extant populations of this
      species. KEY RESULTS: Low genetic diversity (at population level, P = 14.21 %,
      H(E) = 0.0597; at species level, P = 35.90 %, H(T) = 0.1082) and a high degree of
      differentiation among populations (G(ST) = 0.4321) were detected. CONCLUSIONS:
      This genetic structure is considered to be due to the combined effects of slow
      biochemical evolution, genetic drift, inbreeding and limited gene flow between
      populations. Based on these findings, strategies are proposed for the genetic
      conservation and management of the species.

PMID- 15145795
TI  - Ficus rubiginosa 'variegata', a chlorophyll-deficient chimera with mosaic
      patterns created by cell divisions from the outer meristematic layer.
AB  - BACKGROUND AND AIMS: Sections leaves of Ficus rubiginosa 'Variegata' show that it
      is a chimera with a chlorophyll deficiency in the second layer of the leaf
      meristem (GWG structure). Like other Ficus species, it has a multiseriate
      epidermis on the adaxial and abaxial sides of the leaf, formed by periclinal cell
      divisions as well as anticlinal divisions. The upper and lower laminae of the
      leaf often exhibit small dark and light green patches of tissue overlying
      internal leaf tissue. METHODS: The distribution of chlorophyll in transverse
      sections of typical leaves was determined by fluorescence microscopy. KEY
      RESULTS: Patches of dark and light green tissue which arise in the otherwise
      colourless palisade and spongy mesophyll tissue in the entire leaf are due to
      further cell divisions arising from the bundle sheath which is associated with
      major vascular bundles or from the green multiseriate epidermis. Leaves produced
      in winter exhibit more patches of green tissue than leaves which expand in mid
      summer. Many leaves produced in summer have no spotting and appear like a typical
      GWG chimera. There is a strong relationship between the number of patches on the
      adaxial side of leaves and the number on the abaxial side, showing that the cell
      division in upper and lower layers of leaves is strongly coordinated. In both
      winter and summer, there are fewer patches on the abaxial side of leaves compared
      with the adaxial side, indicating that periclinal and anticlinal cell divisions
      from the outer meristematic layer are less frequent in the lower layers of leaf
      tissue. Most of the patches are small (<1 mm in longest dimension) and thus the
      cell divisions which form them occur late in leaf development. Leaves which
      exhibit large patches generally have them on both sides of the leaves.
      CONCLUSION: In this cultivar, the outer meristematic layer appears to form
      vascular bundle sheaths and associated internal leaf tissue in the entire leaf
      lamina.

PMID- 15145794
TI  - Giant shoot apical meristems in cacti have ordinary leaf primordia but altered
      phyllotaxy and shoot diameter.
AB  - BACKGROUND AND AIMS: Shoot apical meristems (SAMs) in most seed plants are quite
      uniform in size and zonation, and molecular genetic studies of Arabidopsis and
      other model plants are revealing details of SAM morphogenesis. Some cacti have
      SAMs much larger than those of A. thaliana and other seed plants. This study
      examined how SAM size affects leaf primordium (LP) size, phyllotaxy and shoot
      diameter. METHODS: Apices from 183 species of cacti were fixed, microtomed and
      studied by light microscopy. KEY RESULTS: Cactus SAM diameter varies from 93 to
      2565 microm, the latter being 36 times wider than SAMs of A. thaliana and having
      a volume 45 thousand times larger. Phyllotaxy ranges from distichous to having 56
      rows of leaves and is not restricted to Fibonacci numbers. Leaf primordium
      diameter ranges from 44 to 402 microm, each encompassing many more cells than do
      LP of other plants. Species with high phyllotaxy have smaller LP, although the
      correlation is weak. There is almost no correlation between SAM diameter and LP
      size, but SAM diameter is strongly correlated with shoot diameter, with shoots
      being about 189.5 times wider than SAMs. CONCLUSIONS: Presumably, genes such as
      SHOOT-MERISTEMLESS, WUSCHEL and CLAVATA must control much larger volumes of SAM
      tissue in cacti than they do in A. thaliana, and genes such as PERIANTHIA might
      establish much more extensive fields of inhibition around LP. These giant SAMs
      should make it possible to more accurately map gene expression patterns relative
      to SAM zonation and LP sites.

PMID- 15145796
TI  - Early events in Agrobacterium-mediated genetic transformation of citrus explants.
AB  - BACKGROUND AND AIMS: Genetic transformation of plants relies on two independent
      but concurrent processes: integration of foreign DNA into plant cells and
      regeneration of whole plants from these transformed cells. Cell competence for
      regeneration and for transformation does not always fall into the same cell
      type/developmental stage, and this is one of the main causes of the so-called
      recalcitrance for transformation of certain plant species. In this study, a
      detailed examination of the first steps of morphogenesis from citrus explants
      after co-cultivation with Agrobacterium tumefaciens was performed, and an
      investigation into which cells and tissues are competent for regeneration and
      transformation was carried out. Moreover, the role of phytohormones in the co
      cultivation medium as possible enhancers of gene transfer was also studied.
      METHODS: A highly responsive citrus genotype and well-established culture
      conditions were used to perform a histological analysis of morphogenesis and cell
      competence for transformation after co-cultivation of citrus epicotyl segments
      with A. tumefaciens. In addition, the role of phytohormones as transformation
      enhancers was investigated by flow cytometry. KEY RESULTS: It is demonstrated
      that cells competent for transformation are located in the newly formed callus
      growing from the cambial ring. Conditions conducive to further development of
      this callus, such as treatment of explants in a medium rich in auxins, resulted
      in a more pronounced formation of cambial callus and a slower shoot regeneration
      process, both in Agrobacterium-inoculated and non-inoculated explants.
      Furthermore, co- cultivation in a medium rich in auxins caused a significant
      increase in the rate of actively dividing cells in S-phase, the stage in which
      cells are more prone to integrate foreign DNA. CONCLUSIONS: Use of proper co
      cultivation medium and conditions led to a higher number of stably transformed
      cells and to an increase in the final number of regenerated transgenic plants.

PMID- 15145797
TI  - Long term follow up study of survival associated with cleft lip and palate at
      birth.
AB  - OBJECTIVE: To assess the overall and cause specific mortality of people from
      birth to 55 years with cleft lip and palate. DESIGN: Long term follow up study.
      SETTING: Danish register of deaths. PARTICIPANTS: People born with cleft lip and
      palate between 1943 and 1987, followed to 1998. MAIN OUTCOME MEASURES: Observed
      and expected numbers of deaths, summarised as overall and cause specific
      standardised mortality ratios. RESULTS: 5331 people with cleft lip and palate
      were followed for 170 421 person years. The expected number of deaths was 259,
      but 402 occurred, corresponding to a standardised mortality ratio of 1.4 (95%
      confidence interval 1.3 to 1.6) for males and 1.8 (1.5 to 2.1) for females. The
      increased risk of mortality was nearly constant for the three intervals at follow
      up: first year of life, 1-17 years, and 18-55 years. The participants had an
      increased risk of all major causes of death. CONCLUSIONS: People with cleft lip
      and palate have increased mortality up to age 55. Children born with cleft lip
      and palate and possibly other congenital malformations may benefit from specific
      preventive health measures into and throughout adulthood.

PMID- 15145798
TI  - A neural network method for prediction of beta-turn types in proteins using
      evolutionary information.
AB  - MOTIVATION: The prediction of beta-turns is an important element of protein
      secondary structure prediction. Recently, a highly accurate neural network based
      method Betatpred2 has been developed for predicting beta-turns in proteins using
      position-specific scoring matrices (PSSM) generated by PSI-BLAST and secondary
      structure information predicted by PSIPRED. However, the major limitation of
      Betatpred2 is that it predicts only beta-turn and non-beta-turn residues and does
      not provide any information of different beta-turn types. Thus, there is a need
      to predict beta-turn types using an approach based on multiple sequence
      alignment, which will be useful in overall tertiary structure prediction.
      RESULTS: In the present work, a method has been developed for the prediction of
      beta-turn types I, II, IV and VIII. For each turn type, two consecutive feed
      forward back-propagation networks with a single hidden layer have been used where
      the first sequence-to-structure network has been trained on single sequences as
      well as on PSI-BLAST PSSM. The output from the first network along with PSIPRED
      predicted secondary structure has been used as input for the second-level
      structure-to-structure network. The networks have been trained and tested on a
      non-homologous dataset of 426 proteins chains by 7-fold cross-validation. It has
      been observed that the prediction performance for each turn type is improved
      significantly by using multiple sequence alignment. The performance has been
      further improved by using a second level structure-to-structure network and
      PSIPRED predicted secondary structure information. It has been observed that Type
      I and II beta-turns have better prediction performance than Type IV and VIII beta
      turns. The final network yields an overall accuracy of 74.5, 93.5, 67.9 and 96.5%
      with MCC values of 0.29, 0.29, 0.23 and 0.02 for Type I, II, IV and VIII beta
      turns, respectively, and is better than random prediction. AVAILABILITY: A web
      server for prediction of beta-turn types I, II, IV and VIII based on above
      approach is available at http://www.imtech.res.in/raghava/betaturns/ and
      http://bioinformatics.uams.edu/mirror/betaturns/ (mirror site).

PMID- 15145799
TI  - GeneRecords: a relational database for GenBank flat file parsing and data
      manipulation in personal computers.
AB  - Extracting the desired data from a database entry for later analysis is a
      constant need in the biological sequence analysis community; GeneRecords 1.0 is a
      solution for GenBank biological flat file parsing, as it implements a structured
      representation of each feature and feature qualifier in GenBank following import
      in a common database managing system usable in a personal computer (Macintosh and
      Windows environments). This collection of related databases enables the local
      management of GenBank records, allowing indexing, retrieval and analysis of both
      information and sequences on a personal computer. AVAILABILITY: The current
      release, including the FileMaker Pro runtime application (built for Windows and
      Macintosh environments), is freely available at
      http://apollo11.isto.unibo.it/software/

PMID- 15145800
TI  - Prediction of similarly acting cis-regulatory modules by subsequence profiling
      and comparative genomics in Drosophila melanogaster and D.pseudoobscura.
AB  - MOTIVATION: To date, computational searches for cis-regulatory modules (CRMs)
      have relied on two methods. The first, phylogenetic footprinting, has been used
      to find CRMs in non-coding sequence, but does not directly link DNA sequence with
      spatio-temporal patterns of expression. The second, based on searches for
      combinations of transcription factor (TF) binding motifs, has been employed in
      genome-wide discovery of similarly acting enhancers, but requires prior knowledge
      of the set of TFs acting at the CRM and the TFs' binding motifs. RESULTS: We
      propose a method for CRM discovery that combines aspects of both approaches in an
      effort to overcome their individual limitations. By treating phylogenetically
      footprinted non-coding regions (PFRs) as proxies for CRMs, we endeavor to find
      PFRs near co-regulated genes that are comprised of similar short, conserved
      sequences. Using Markov chains as a convenient formulation to assess similarity,
      we develop a sampling algorithm to search a large group of PFRs for the most
      similar subset. When starting with a set of genes involved in Drosophila early
      blastoderm development and using phylogenetic comparisons of Drosophila
      melanogaster and D.pseudoobscura genomes, we show here that our algorithm
      successfully detects known CRMs. Further, we use our similarity metric, based on
      Markov chain discrimination, in a genome-wide search, and uncover additional
      known and many candidate early blastoderm CRMs. AVAILABILITY: Software is
      available via http://arep.med.harvard.edu/enhancer

PMID- 15145801
TI  - The Global Error Assessment (GEA) model for the selection of differentially
      expressed genes in microarray data.
AB  - MOTIVATION: Microarray technology has become a powerful research tool in many
      fields of study; however, the cost of microarrays often results in the use of a
      low number of replicates (k). Under circumstances where k is low, it becomes
      difficult to perform standard statistical tests to extract the most biologically
      significant experimental results. Other more advanced statistical tests have been
      developed; however, their use and interpretation often remain difficult to
      implement in routine biological research. The present work outlines a method that
      achieves sufficient statistical power for selecting differentially expressed
      genes under conditions of low k, while remaining as an intuitive and
      computationally efficient procedure. RESULTS: The present study describes a
      Global Error Assessment (GEA) methodology to select differentially expressed
      genes in microarray datasets, and was developed using an in vitro experiment that
      compared control and interferon-gamma treated skin cells. In this experiment, up
      to nine replicates were used to confidently estimate error, thereby enabling
      methods of different statistical power to be compared. Gene expression results of
      a similar absolute expression are binned, so as to enable a highly accurate local
      estimate of the mean squared error within conditions. The model then relates
      variability of gene expression in each bin to absolute expression levels and uses
      this in a test derived from the classical ANOVA. The GEA selection method is
      compared with both the classical and permutational ANOVA tests, and demonstrates
      an increased stability, robustness and confidence in gene selection. A subset of
      the selected genes were validated by real-time reverse transcription-polymerase
      chain reaction (RT-PCR). All these results suggest that GEA methodology is (i)
      suitable for selection of differentially expressed genes in microarray data, (ii)
      intuitive and computationally efficient and (iii) especially advantageous under
      conditions of low k. AVAILABILITY: The GEA code for R software is freely
      available upon request to authors.

PMID- 15145802
TI  - A Bayesian connectivity-based approach to constructing probabilistic gene
      regulatory networks.
AB  - MOTIVATION: We have hypothesized that the construction of transcriptional
      regulatory networks using a method that optimizes connectivity would lead to
      regulation consistent with biological expectations. A key expectation is that the
      hypothetical networks should produce a few, very strong attractors, highly
      similar to the original observations, mimicking biological state stability and
      determinism. Another central expectation is that, since it is expected that the
      biological control is distributed and mutually reinforcing, interpretation of the
      observations should lead to a very small number of connection schemes. RESULTS:
      We propose a fully Bayesian approach to constructing probabilistic gene
      regulatory networks (PGRNs) that emphasizes network topology. The method computes
      the possible parent sets of each gene, the corresponding predictors and the
      associated probabilities based on a nonlinear perceptron model, using a
      reversible jump Markov chain Monte Carlo (MCMC) technique, and an MCMC method is
      employed to search the network configurations to find those with the highest
      Bayesian scores to construct the PGRN. The Bayesian method has been used to
      construct a PGRN based on the observed behavior of a set of genes whose
      expression patterns vary across a set of melanoma samples exhibiting two very
      different phenotypes with respect to cell motility and invasiveness. Key
      biological features have been faithfully reflected in the model. Its steady-state
      distribution contains attractors that are either identical or very similar to the
      states observed in the data, and many of the attractors are singletons, which
      mimics the biological propensity to stably occupy a given state. Most
      interestingly, the connectivity rules for the most optimal generated networks
      constituting the PGRN are remarkably similar, as would be expected for a network
      operating on a distributed basis, with strong interactions between the
      components.

PMID- 15145803
TI  - Transcription/replication collisions cause bacterial transcription units to be
      longer on the leading strand of replication.
AB  - MOTIVATION: The costs of head-on versus codirectional collisions between the
      replication complex and the much slower transcription complex on the circular
      bacterial chromosomes are much debated. Although it is established that the
      number of genes on the leading strand is higher than on the lagging strand of
      replication, the consequences of collisions on the length of transcription units
      are unknown. RESULTS: Here, we show that transcription units are generally longer
      on the leading strand, in rough proportion to the bias in number of units between
      the two strands. We propose a statistical physics model, based on the assumption
      that the proportion of interrupted transcripts for each unit is the major factor
      contributing to these biases. Its main prediction is that a large
      replication/transcription speed ratio implies a low leading/lagging bias for
      transcription unit length and number. This model is validated by an analysis of
      proven and predicted units in Escherichia coli and Bacillus subtilis. The results
      are consistent with an equal cost of head-on versus codirectional collisions.

PMID- 15145804
TI  - FigSearch: a figure legend indexing and classification system.
AB  - FigSearch is a prototype text-mining and classification system for figures from
      any corpus of full-text biological papers. The system allows users to search for
      figures that contain genes of interest and illustrate protein interactions. The
      retrieved figures are ranked by a score representing the likelihood to be of a
      certain type, in this case, schematic illustrations of protein interactions and
      signaling events. The system contains a Web interface for search, a module for
      classification of figures based on vector representations of figure legends and a
      module for indexing gene names. In a preliminary validation, the FigSearch system
      showed satisfactory performance according to domain experts in providing the most
      relevant graphical representations. This strategy may be easily extended to other
      figure types. Moreover, as more full-text data become available, such a system
      will find increased usefulness in identifying and presenting compressed
      biological knowledge. AVAILABILITY: A searchable Web interface, FigSearch, is
      accessible via http://pubgeneserver.uio.no/figsearch/ for all figures from the
      available corpus.

PMID- 15145805
TI  - TigrScan and GlimmerHMM: two open source ab initio eukaryotic gene-finders.
AB  - We describe two new Generalized Hidden Markov Model implementations for ab initio
      eukaryotic gene prediction. The C/C++ source code for both is available as open
      source and is highly reusable due to their modular and extensible architectures.
      Unlike most of the currently available gene-finders, the programs are re
      trainable by the end user. They are also re-configurable and include several
      types of probabilistic submodels which can be independently combined, such as
      Maximal Dependence Decomposition trees and interpolated Markov models. Both
      programs have been used at TIGR for the annotation of the Aspergillus fumigatus
      and Toxoplasma gondii genomes. AVAILABILITY: Source code and documentation are
      available under the open source Artistic License from
      http://www.tigr.org/software/pirate

PMID- 15145806
TI  - Thermodynamics of enzyme-catalyzed reactions--a database for quantitative
      biochemistry.
AB  - The Thermodynamics of Enzyme-catalyzed Reactions Database (TECRDB) is a
      comprehensive collection of thermodynamic data on enzyme-catalyzed reactions. The
      data, which consist of apparent equilibrium constants and calorimetrically
      determined molar enthalpies of reaction, are the primary experimental results
      obtained from thermodynamic studies of biochemical reactions. The results from
      approximately 1000 published papers containing data on approximately 400
      different enzyme-catalyzed reactions constitute the essential information in the
      database. The information is managed using Oracle and is available on the Web.
      AVAILABILITY: http://xpdb.nist.gov/enzyme_thermodynamics/

PMID- 15145807
TI  - Rainbow: a toolbox for phylogenetic supertree construction and analysis.
AB  - Rainbow is a program that provides a graphic user interface to construct
      supertrees using different methods. It also provides tools to analyze the quality
      of the supertrees produced. Rainbow is available for Mac OS X, Windows and Linux.
      AVAILABILITY: Rainbow is a free open-source software. Its binary files, source
      code, and manual can be downloaded from the Rainbow web page:
      http://genome.cs.iastate.edu/Rainbow/

PMID- 15145808
TI  - Mining gene expression data for positive and negative co-regulated gene clusters.
AB  - MOTIVATION: Analysis of gene expression data can provide insights into the
      positive and negative co-regulation of genes. However, existing methods such as
      association rule mining are computationally expensive and the quality and
      quantities of the rules are sensitive to the support and confidence values. In
      this paper, we introduce the concept of positive and negative co-regulated gene
      cluster (PNCGC) that more accurately reflects the co-regulation of genes, and
      propose an efficient algorithm to extract PNCGCs. RESULTS: We experimented with
      the Yeast dataset and compared our resulting PNCGCs with the association rules
      generated by the Apriori mining algorithm. Our results show that our PNCGCs
      identify some missing co-regulations of association rules, and our algorithm
      greatly reduces the large number of rules involving uncorrelated genes generated
      by the Apriori scheme. AVAILABILITY: The software is available upon request.

PMID- 15145809
TI  - Exhaustive whole-genome tandem repeats search.
AB  - MOTIVATION: Approximate tandem repeats (ATR) occur frequently in the genomes of
      organisms, and are a source of polymorphisms observed in individuals, and thus
      are of interest to those studying genetic disorders. Though extensive work has
      been done in order to identify ATRs, there are inherent limitations with the
      current approaches in terms of the number of pattern sizes that can be searched
      or the size of the input length. RESULTS: This paper describes (1) a new
      algorithm which exhaustively finds all variable-length ATRs in a genomic sequence
      and (2) a precise description of, and an algorithm to significantly reduce,
      redundancy in the output. Our ATR definition is parameterized by a mismatch ratio
      p which allows for more mismatches in longer tandem repeats (and fewer in
      shorter). Furthermore, our algorithm is embarrassingly parallel and thus can
      attain near-linear speed-up on Beowulf clusters. We present results of our
      algorithm applied to sequences of widely differing lengths (from genes to
      chromosomes). AVAILABILITY: Source and binaries are available on request.

PMID- 15145810
TI  - A mixture model for estimating the local false discovery rate in DNA microarray
      analysis.
AB  - MOTIVATION: Statistical methods based on controlling the false discovery rate
      (FDR) or positive false discovery rate (pFDR) are now well established in
      identifying differentially expressed genes in DNA microarray. Several authors
      have recently raised the important issue that FDR or pFDR may give misleading
      inference when specific genes are of interest because they average the genes
      under consideration with genes that show stronger evidence for differential
      expression. The paper proposes a flexible and robust mixture model for estimating
      the local FDR which quantifies how plausible each specific gene expresses
      differentially. RESULTS: We develop a special mixture model tailored to multiple
      testing by requiring the P-value distribution for the differentially expressed
      genes to be stochastically smaller than the P-value distribution for the non
      differentially expressed genes. A smoothing mechanism is built in. The proposed
      model gives robust estimation of local FDR for any reasonable underlying P-value
      distributions. It also provides a single framework for estimating the proportion
      of differentially expressed genes, pFDR, negative predictive values, sensitivity
      and specificity. A cervical cancer study shows that the local FDR gives more
      specific and relevant quantification of the evidence for differential expression
      that can be substantially different from pFDR. AVAILABILITY: An R function
      implementing the proposed model is available at
      http://www.geocities.com/jg_liao/software

PMID- 15145811
TI  - Correcting log ratios for signal saturation in cDNA microarrays.
AB  - MOTIVATION: Pixel saturation occurs when the pixel intensity exceeds a threshold
      and the recorded pixel intensity is truncated. Microarray experiments are
      commonly afflicted with saturated pixels. As a result, estimators of gene
      expression are biased, with the amount of bias increasing as a function of the
      proportion of pixels saturated. Saturation is directly related to the
      photomultiplier tube (PMT) voltage settings and RNA abundance and is not
      necessarily associated with poor array or poor spot quality. When choosing PMT
      settings, higher PMT settings are desired because of improved signal-to-noise
      ratios of low-intensity spots. This improved signal is somewhat offset by
      saturation of high-intensity spots. In practice, spots with saturated pixels are
      discarded or the biased value is used. Neither of these approaches is appealing,
      particularly the former approach when a highly expressed gene is discarded
      because of saturation. RESULTS: We present a method to correct for saturation
      using pixel-level data. The method is based on a censored regression model.
      Evaluations on several arrays indicate that the method performs well. Simulation
      studies suggest that the method is robust under certain model violations.

PMID- 15145813
TI  - ClutrFree: cluster tree visualization and interpretation.
AB  - ClutrFree facilitates the visualization and interpretation of clusters or
      patterns computed from microarray data through a graphical user interface that
      displays patterns, membership information of the genes and annotation statistics
      simultaneously. ClutrFree creates a tree linking the patterns based on
      similarity, permitting the navigation among patterns identified by different
      algorithms or by the same algorithm with different parameters, and aids the
      inferring of conclusions from a microarray experiment. AVAILABILITY: The
      ClutrFree Java source code and compiled bytecode are available as a package under
      the GNU General Public License at http://bioinformatics.fccc.edu

PMID- 15145812
TI  - An efficient algorithm for optimizing whole genome alignment with noise.
AB  - MOTIVATION: This paper is concerned with algorithms for aligning two whole
      genomes so as to identify regions that possibly contain conserved genes.
      Motivated by existing heuristic-based software tools, we initiate the study of an
      optimization problem that attempts to uncover conserved genes with a global
      concern. Another interesting feature in our formulation is the tolerance of
      noise, which also complicates the optimization problem. A brute-force approach
      takes time exponential in the noise level. RESULTS: We show how an insight into
      the optimization structure can lead to a drastic improvement in the time and
      space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the
      size of the input and k is the noise level]. The reduced space requirement allows
      us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting
      to see that when tested with different real data sets, MaxMinCluster consistently
      uncovers a high percentage of conserved genes that have been published by
      GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most
      popular software tool for uncovering conserved genes in a whole-genome scale).
      AVAILABILITY: The source code is available from the website
      http://www.csis.hku.hk/~colly/maxmincluster/ detailed proof of the propositions
      can also be found there.

PMID- 15145814
TI  - Prokaryotic diversity of the Saccharomyces cerevisiae Atx1p-mediated copper
      pathway.
AB  - MOTIVATION: Several genes involved in the cellular import of copper and its
      subsequent incorporation into the high-affinity iron transport complex in
      Saccharomyces cerevisiae are known to be conserved between eukaryotes and
      prokaryotes. However, the degree to which these genes share their functional
      context as members of the same pathway in the prokaryotic domain is less clear.
      RESULTS: The co-occurrence of gene families involved in Atx1p-mediated copper
      transport in the genomes and operon structures of 80 non-redundant prokaryotes
      was investigated. For this purpose, we developed a Web tool (SHOPS) to display
      the operon context for a given set of proteins. In total, a set of 43 putative
      operons was identified. These were found to be involved in a variety of pathways
      and indicate a large diversity in the functional context of the individual gene
      family members. AVAILABILITY: The SHOPS tool can be found at
      http://www.bioinformatics.med.uu.nl/shops supplemental data are available at
      http://humgen.med.uu.nl/publications/vanbakel/pathway/

PMID- 15145815
TI  - Dblox: a genome-wide test for ancient segmental duplication.
AB  - Dblox and RDblox provide a simple statistical test for duplicated genomic
      structure; the same programs can also be used to identify putatively duplicated
      regions. The method focuses on ancient duplication events involving protein
      coding genes. AVAILABILITY: http://www.biol.sc.edu/~austin/

PMID- 15145817
TI  - Pathway Miner: extracting gene association networks from molecular pathways for
      predicting the biological significance of gene expression microarray data.
AB  - We have developed a web-based system (Pathway Miner) for visualizing gene
      expression profiles in the context of biological pathways. Pathway Miner catalogs
      genes based on their role in metabolic, cellular and regulatory pathways. A
      Fisher exact test is provided as an option to rank pathways. The genes are mapped
      onto pathways and gene product association networks are extracted for genes that
      co-occur in pathways. The networks can be filtered for analysis based on user
      selected options. AVAILABILITY: Pathway Miner is a freely available web
      accessible tool at http://www.biorag.org/pathway.html

PMID- 15145816
TI  - Algorithms for sequence analysis via mutagenesis.
AB  - MOTIVATION: Despite many successes of conventional DNA sequencing methods, some
      DNAs remain difficult or impossible to sequence. Unsequenceable regions occur in
      the genomes of many biologically important organisms, including the human genome.
      Such regions range in length from tens to millions of bases, and may contain
      valuable information such as the sequences of important genes. The authors have
      recently developed a technique that renders a wide range of problematic DNAs
      amenable to sequencing. The technique is known as sequence analysis via
      mutagenesis (SAM). This paper presents a number of algorithms for analysing and
      interpreting data generated by this technique. RESULTS: The essential idea of SAM
      is to infer the target sequence using the sequences of mutants derived from the
      target. We describe three algorithms used in this process. The first algorithm
      predicts the number of mutants that will be required to infer the target sequence
      with a desired level of accuracy. The second algorithm infers the target sequence
      itself, using the mutant sequences. The third algorithm assigns quality values to
      each inferred base. The algorithms are illustrated using mutant sequences
      generated in the laboratory.

PMID- 15145818
TI  - An object model and database for functional genomics.
AB  - MOTIVATION: Large-scale functional genomics analysis is now feasible and presents
      significant challenges in data analysis, storage and querying. Data standards are
      required to enable the development of public data repositories and to improve
      data sharing. There is an established data format for microarrays (microarray
      gene expression markup language, MAGE-ML) and a draft standard for proteomics
      (PEDRo). We believe that all types of functional genomics experiments should be
      annotated in a consistent manner, and we hope to open up new ways of comparing
      multiple datasets used in functional genomics. RESULTS: We have created a
      functional genomics experiment object model (FGE-OM), developed from the
      microarray model, MAGE-OM and two models for proteomics, PEDRo and our own model
      (Gla-PSI-Glasgow Proposal for the Proteomics Standards Initiative). FGE-OM
      comprises three namespaces representing (i) the parts of the model common to all
      functional genomics experiments; (ii) microarray-specific components; and (iii)
      proteomics-specific components. We believe that FGE-OM should initiate discussion
      about the contents and structure of the next version of MAGE and the future of
      proteomics standards. A prototype database called RNA And Protein Abundance
      Database (RAPAD), based on FGE-OM, has been implemented and populated with data
      from microbial pathogenesis. AVAILABILITY: FGE-OM and the RAPAD schema are
      available from http://www.gusdb.org/fge.html, along with a set of more detailed
      diagrams. RAPAD can be accessed by registration at the site.

PMID- 15145819
TI  - Sympatho-modulatory therapies in perioperative medicine.

PMID- 15145820
TI  - Cellular mechanisms in sympatho-modulation of the heart.
AB  - Cardiovascular function relies on complex servo-controlled regulation mechanisms
      that involve both fast-acting feedback responses and long-lasting adaptations
      affecting the gene expression. The adrenergic system, with its specific receptor
      subtypes and intracellular signalling cascades provides the major regulatory
      system, while the parasympathetic system plays a minor role. At the molecular
      level, Ca(2+) acts as the general signal trigger for the majority of cell
      activities including contraction, metabolism and growth. During recent years,
      important new results have emerged allowing an integrated view of how the
      multifarious Ca(2+)-signalling mechanisms transmit adrenergic impulses to
      intracellular target sites. These insights into cellular and molecular mechanisms
      are pivotal in improving pharmacological control of the sympathetic responses to
      surgical trauma and perioperative stress. They are examined in detail in this
      review, with particular emphasis being given to the differences in intracellular
      signalling between cardiomyocytes and vascular smooth muscle cells.

PMID- 15145821
TI  - Perioperative cardiac arrhythmias.

PMID- 15145822
TI  - Heart failure.

PMID- 15145823
TI  - Genomics and the circulation.

PMID- 15145824
TI  - Myocardial injury and its prevention in the perioperative setting.

PMID- 15145825
TI  - A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive
      heterochromatin.
AB  - Histone lysine methylation is a central modification to mark functionally
      distinct chromatin regions. In particular, H3-K9 trimethylation has emerged as a
      hallmark of pericentric heterochromatin in mammals. Here we show that H4-K20
      trimethylation is also focally enriched at pericentric heterochromatin.
      Intriguingly, H3-K9 trimethylation by the Suv39h HMTases is required for the
      induction of H4-K20 trimethylation, although the H4 Lys 20 position is not an
      intrinsic substrate for these enzymes. By using a candidate approach, we
      identified Suv4-20h1 and Suv4-20h2 as two novel SET domain HMTases that localize
      to pericentric heterochromatin and specifically act as nucleosomal H4-K20
      trimethylating enzymes. Interaction of the Suv4-20h enzymes with HP1 isoforms
      suggests a sequential mechanism to establish H3-K9 and H4-K20 trimethylation at
      pericentric heterochromatin. Heterochromatic H4-K20 trimethylation is
      evolutionarily conserved, and in Drosophila, the Suv4-20 homolog is a novel PEV
      modifier to regulate position-effect variegation. Together, our data indicate a
      function for H4-K20 trimethylation in gene silencing and further suggest H3-K9
      and H4-K20 trimethylation as important components of a repressive pathway that
      can index pericentric heterochromatin.

PMID- 15145826
TI  - Alkylating DNA damage stimulates a regulated form of necrotic cell death.
AB  - Necrosis has been considered a passive form of cell death in which the cell dies
      as a result of a bioenergetic catastrophe imposed by external conditions.
      However, in response to alkylating DNA damage, cells undergo necrosis as a self
      determined cell fate. This form of death does not require the central apoptotic
      mediators p53, Bax/Bak, or caspases and actively induces an inflammatory
      response. Necrosis in response to DNA damage requires activation of the DNA
      repair protein poly(ADP-ribose) polymerase (PARP), but PARP activation is not
      sufficient to determine cell fate. Cell death is determined by the effect of PARP
      mediated beta-nicotinamide adenine dinucleotide (NAD) consumption on cellular
      metabolism. Cells using aerobic glycolysis to support their bioenergetics undergo
      rapid ATP depletion and death in response to PARP activation. In contrast, cells
      catabolizing nonglucose substrates to maintain oxidative phosphorylation are
      resistant to ATP depletion and death in response to PARP activation. Because most
      cancer cells maintain their ATP production through aerobic glycolysis, these data
      may explain the molecular basis by which DNA-damaging agents can selectively
      induce tumor cell death independent of p53 or Bcl-2 family proteins.

PMID- 15145829
TI  - Editorial I: powerful tools require careful handling--the case of the circadian
      ketamine effect.

PMID- 15145827
TI  - Computational definition of sequence motifs governing constitutive exon splicing.
AB  - We have searched for sequence motifs that contribute to the recognition of human
      pre-mRNA splice sites by comparing the frequency of 8-mers in internal noncoding
      exons versus unspliced pseudo exons and 5' untranslated regions (5' untranslated
      regions [UTRs]) of transcripts of intronless genes. This type of comparison
      avoids the isolation of sequences that are distinguished by their protein-coding
      information. We classified sequence families comprising 2069 putative exonic
      enhancers and 974 putative exonic silencers. Representatives of each class
      functioned as enhancers or silencers when inserted into a test exon and assayed
      in transfected mammalian cells. As a class, the enhancer sequencers were more
      prevalent and the silencer elements less prevalent in all exons compared with
      introns. A survey of 58 reported exonic splicing mutations showed good agreement
      between the splicing phenotype and the effect of the mutation on the motifs
      defined here. The large number of effective sequences implied by these results
      suggests that sequences that influence splicing may be very abundant in pre-mRNA.

PMID- 15145830
TI  - Editorial II: not waving, but drowning.

PMID- 15145831
TI  - Editorial III: xenon--cardiovascularly inert?

PMID- 15145832
TI  - Editorial IV: physical and pharmacological restraint of critically ill patients:
      clinical facts and ethical considerations.

PMID- 15145828
TI  - Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S.
      cerevisiae.
AB  - The tRNA m(1)A58 methyltransferase is composed of two subunits encoded by the
      essential genes TRM6 and TRM61 (formerly GCD10 and GCD14). The trm6-504 mutation
      results in a defective m(1)A methyltransferase (Mtase) and a temperature
      sensitive growth phenotype that is attributable to the absence of m(1)A58 and
      consequential tRNA(i)(Met) instability. We used a genetic approach to identify
      the genes responsible for tRNA(i)(Met) degradation in trm6 cells. Three recessive
      extragenic mutations that suppress trm6-504 mutant phenotypes and restore
      hypomodified tRNA(i)(Met) to near normal levels were identified. The wild-type
      allele of one suppressor, DIS3/RRP44, encodes a 3'-5' exoribonuclease and a
      member of the multisubunit exosome complex. We provide evidence that a functional
      nuclear exosome is required for the degradation of tRNA(i)(Met) lacking m(1)A58.
      A second suppressor gene encodes Trf4p, a DNA polymerase (pol sigma) with poly(A)
      polymerase activity. Whereas deletion of TRF4 leads to stabilization of
      tRNA(i)(Met), overexpression of Trf4p destabilizes the hypomodified tRNA(i)(Met)
      in trm6 cells. The hypomodified, but not wild-type, pre-tRNA(i)(Met) accumulates
      as a polyadenylated species, whose abundance and length distribution both
      increase upon Trf4p overexpression. These data indicate that a tRNA surveillance
      pathway exists in yeast that requires Trf4p and the exosome for polyadenylation
      and degradation of hypomodified pre-tRNA(i)(Met).

PMID- 15145834
TI  - Obstetric epidurals and chronic adhesive arachnoiditis.

PMID- 15145833
TI  - Gender differences in baroreflex response and heart rate variability in
      anaesthetized humans.
AB  - BACKGROUND: In conscious humans, men have a greater cardiovagal baroreflex gain
      than women. We studied gender-related differences in baroreflex function during
      general anaesthesia. METHODS: Sixty healthy patients (30 male and 30 female) were
      anaesthetized with sevoflurane 2% end-tidal in air and oxygen, and their lungs
      were mechanically ventilated. We recorded the ECG and invasive arterial pressure.
      Baroreflex gain was measured as the linear relationship of R-R interval with
      systolic arterial pressure changes caused by doses of phenylephrine i.v., and
      also the spontaneous changes in R-R interval and arterial pressure. In addition,
      consecutive R-R intervals were analysed using a fast Fourier transformation.
      RESULTS: Baroreflex gains (mean (sd)) assessed by the pharmacological method in
      men (7.98 (5.12) ms x mm x Hg(-1)) was significantly greater than that in women
      (4.89 (3.87) ms x mm x Hg(-1)). Similarly, spontaneous baroreflex gains were
      significantly greater in men than in women, and correlated well with high
      frequency power, but not with low-frequency power or low/high ratio, of heart
      rate variability in both genders. CONCLUSIONS: Our results extend findings in
      conscious humans to sevoflurane anaesthesia. Men have greater cardiovagal reflex
      gains than women, which may reflect differences in parasympathetic action on
      heart rate.

PMID- 15145835
TI  - Use of the ProSeal laryngeal mask airway for airway maintenance during emergency
      Caesarean section after failed intubation.

PMID- 15145836
TI  - Tracheostomy in a patient with SARS.

PMID- 15145837
TI  - Another case of use of the ProSeal laryngeal mask airway in a difficult obstetric
      airway.

PMID- 15145838
TI  - Protective ventilation of patients with ARDS.

PMID- 15145839
TI  - Oesophagectomy and elective postoperative ventilation.

PMID- 15145840
TI  - Endotoxaemia during left ventricular assist device insertion.

PMID- 15145841
TI  - Epidurals in septic patients.

PMID- 15145842
TI  - Sub-Tenon's block: are fasting and intravenous access necessary?

PMID- 15145843
TI  - Bupivacaine in the sub-Tenon's space to relieve postoperative pain in a child.

PMID- 15145844
TI  - Unrestricted sips of water before Caesarean section.

PMID- 15145845
TI  - Endothelial progenitor cells and coronary artery disease.
AB  - Endothelial progenitor cells have radically altered the way in which vascular
      biologists and clinicians think about the genesis, development, and healing of
      atherosclerotic lesions.

PMID- 15145846
TI  - Twiddler's syndrome in a biventricular implantable cardioverter-defibrillator.

PMID- 15145847
TI  - Physiologic pacing: where pacing mode selection reflects the indication.
AB  - Results of recent trials suggest that in patients with left ventricular
      dysfunction, interventricular synchrony is possibly more important than
      atrioventricular synchrony. In patients with AV block and conduction system
      disease, alternatives to right ventricular apical pacing are therefore needed.

PMID- 15145849
TI  - Myocardial abscess.

PMID- 15145848
TI  - Ethnic variations in acute coronary syndromes.
AB  - Although it is very likely that ethnic variations in the incidence and, possibly,
      clinical outcome of acute coronary artery disease events exist, the causes for
      such differences are many and difficult to address fully, given the complex
      interplay of contributing factors.

PMID- 15145850
TI  - Should antioxidant status be considered in interventional trials with
      antioxidants?
AB  - The last decade has seen many trials with antioxidants in patients with
      cardiovascular disease, with equivocal results. One possible explanation for the
      disappointing findings is the lack of identification criteria of patients who are
      potential candidates for antioxidant treatment. Several studies have been carried
      out in patients at risk of cardiovascular disease, indicating that enhanced
      oxidative stress is associated with the presence of diabetes,
      hypercholesterolaemia, hypertension, and smoking. This review analyses the data
      reported so far to determine whether they clearly support the premise that
      patients at risk of cardiovascular events may be candidates for antioxidant
      treatment.

PMID- 15145855
TI  - Diagnostic criteria and problems in infective endocarditis.

PMID- 15145852
TI  - British Cardiac Society Working Group on the definition of myocardial infarction.
AB  - The British Cardiac Society commissioned this report to help address
      inconsistencies in the terminology for acute coronary syndromes and wide
      variations in the threshold for the diagnosis of myocardial infarction (MI)
      depending on the assay performed, the precision, and the sensitivity. In
      addition, several publications have highlighted potential problems with the
      application of the European Society of Cardiology(ESC)/American College of
      Cardiology (ACC) consensus document published in 2000. A revision process has
      been initiated under the guidance of the ESC, the ACC, and the American Heart
      Association (AHA). The purpose of this report is to help inform the next revision
      of the ESC/ACC/AHA guidelines for the diagnosis of MI.

PMID- 15145857
TI  - Improvement of cardiac hypertrophy and ventricular function in a man with Fabry
      disease by treatment with recombinant alpha-galactosidase A.

PMID- 15145856
TI  - Echocardiography in infective endocarditis.

PMID- 15145859
TI  - Mitral and tricuspid valve thrombus in antiphospholipid syndrome.

PMID- 15145858
TI  - Indications and optimal timing for surgery in infective endocarditis.

PMID- 15145861
TI  - Cardiac haematoma after coronary angioplasty.

PMID- 15145860
TI  - Ethnic variations in female vulnerability after an acute coronary event.
AB  - OBJECTIVE: To determine the ethnic variation of short and long term female
      vulnerability after an acute coronary event in a population of Chinese, Indians,
      and Malays. DESIGN: Population based registry. PATIENTS: Residents of Singapore
      between the ages of 20-64 years with coronary events. Case identification and
      classification procedures were modified from the MONICA (monitoring trends and
      determinants in cardiovascular disease) project. MAIN OUTCOME MEASURES: Adjusted
      28 day case fatality and long term mortality. RESULTS: From 1991 to 1999, there
      were 16 320 acute coronary events, including 3497 women. Age adjusted 28 day case
      fatality was greater in women (51.5% v 38.6%, p < 0.001), with a larger sex
      difference evident among younger Malay patients. This inequality between the
      sexes was observed in both the pre-hospitalisation and post-admission periods.
      Among hospitalised patients, women were older, were less likely to have suffered
      from a previous Q wave or anterior wall myocardial infarction, and had lower peak
      creatine kinase concentrations. Case fatality was higher among women, with
      adjusted hazard ratios of 1.64 (95% confidence interval (CI) 1.43 to 1.88) and
      1.50 (95% CI 1.37 to 1.64) for 28 day and mean four year follow up periods. There
      were significant interactions of sex and age with ethnic group (p = 0.017). The
      adjusted hazards for mortality among Chinese, Indian, and Malay women versus men
      were 1.30, 1.71, and 1.96, respectively. The excess mortality among women
      diminished with age. CONCLUSION: In this multiethnic population, both pre
      hospitalisation and post-admission case fatality rates were substantially higher
      among women. The sex discrepancy in long term mortality was greatest among Malays
      and in the younger age groups.

PMID- 15145862
TI  - Possible angina detected by the WHO angina questionnaire in apparently healthy
      men with a normal exercise ECG: coronary heart disease or not? A 26 year follow
      up study.
AB  - OBJECTIVE: To determine whether men with possible angina (from their responses to
      the World Health Organization angina questionnaire) but a normal exercise ECG
      differ in long term rates of coronary heart disease events from men with no
      symptoms of angina. DESIGN: During 1972-75, 2014 apparently healthy men aged 40
      59 years underwent an examination programme including case history, clinical
      examination, exercise ECG to exhaustion, and various other tests. All men
      completed the WHO angina questionnaire. SUBJECTS: Of 2014 men, 68 had possible
      angina, 1831 had no symptoms of angina, and 115 were excluded because they had
      definite angina or pathological exercise ECGs. All 68+1831 had normal exercise
      ECGs and none developed chest pain during the exercise test. RESULTS: At 26
      years, men with possible angina had a coronary heart disease mortality of 25.0%
      (17/68) v 13.8% (252/1831) among men with no symptoms of angina (p < 0.013). They
      also had a higher incidence of coronary artery bypass grafting (CABG) (p <
      0.0004) and acute myocardial infarction (p < 0.026). The excess coronary heart
      disease mortality among men with possible angina only started after 15 years,
      whereas differences in CABG/acute myocardial infarction started early.
      Multivariate analysis including well recognised coronary heart disease risk
      factors showed that possible angina was an independent risk factor (relative risk
      1.79, 95% confidence interval 1.26 to 2.10). CONCLUSIONS: Men with possible
      angina, even with a normal exercise test, have a greater risk of dying from
      coronary heart disease, having an acute myocardial infarct, or needing a CABG
      than age matched counterparts with no symptoms of angina.

PMID- 15145863
TI  - Minimal invasive direct revascularisation of the left anterior descending artery
      using a novel magnetic vascular anastomotic device.

PMID- 15145864
TI  - Increased cardiac troponin I on admission predicts in-hospital mortality in acute
      pulmonary embolism.
AB  - BACKGROUND: To investigate the frequency of cardiac troponin I (cTnI) increases
      in patients with pulmonary embolism (PE) and to assess the correlation between
      this finding, the clinical presentation, and outcomes. METHODS: Consecutive
      patients admitted to the coronary care unit with acute PE were prospectively
      enrolled between January 2000 and December 2001. cTnI was sequentially
      determined. Various cut off concentrations were analysed, but patients were
      categorised prospectively as having increased or no increased cTnI based on a cut
      off concentration of 0.6 ng/ml. The main outcome measure was in-hospital
      mortality. RESULTS: On admission, 14 of the 48 patients (29%) had cTnI
      concentrations greater than the receiver operating characteristic curve value
      used to diagnose acute myocardial infarction (> 0.6 ng/ml). Subsequently, six
      patients developed increases for an overall prevalence of 42% (20 of 42). The
      prevalence was higher when lower cut off concentrations were used: 73% (35 of 48)
      at the 99th centile and 60% (29 of 48) at the 10% coefficient of variability.
      Increased cTnI > 0.6 ng/ml was associated with a slower oxygen saturation (86
      (7)% v 93 (4)%, p < 0.0001) and more frequent involvement of the main pulmonary
      arteries as assessed by spiral computed tomography (100% v 60%, p = 0.022). In
      hospital mortality was 36% (5 of 14) of patients with increases > 0.6 ng/ml v 3%
      (1 of 42) of patients with lower concentrations (p = 0.008). Increased cTnI > 0.6
      ng/ml on admission was the most powerful predictor of mortality (p = 0.046).
      CONCLUSIONS: In high risk patients with acute PE, cTnI was frequently detected on
      admission. It was the strongest independent predictor of mortality.

PMID- 15145865
TI  - Percutaneous treatment of giant coronary aneurysm with multiple
      polytetrafluoroethylene (PTFE) covered stents.

PMID- 15145866
TI  - Transcoronary ablation of septal hypertrophy for hypertrophic obstructive
      cardiomyopathy: feasibility, clinical benefit, and short term results in elderly
      patients.
AB  - OBJECTIVE: To evaluate symptomatic and haemodynamic results of transcoronary
      ablation of septal hypertrophy for hypertrophic obstructive cardiomyopathy in
      elderly patients. SETTING: Tertiary referral centre for patients with
      hypertrophic obstructive cardiomyopathy. DESIGN: Retrospective study of two
      groups of consecutive patients divided at a median age (59 years). PATIENTS:
      Transcoronary ablation of septal hypertrophy was compared for 80 patients (group
      1) < 60 years of age and 77 patients (group 2) > or = 60 years of age. At
      baseline both groups were similar concerning the proportion of familial
      hypertrophic cardiomyopathy, concomitant moderate hypertension, prior syncope,
      left ventricular outflow obstruction, left ventricular end diastolic pressure,
      and left ventricular ejection fraction. Patients in group 2 had a lower
      interventricular septal thickness and more severe disease as measured by New York
      Heart Association (NYHA) functional class, exercise capacity, pulmonary artery
      mean pressure at workload, and cardiac index at peak exercise. RESULTS: Median
      follow up was seven months after transcoronary ablation of septal hypertrophy.
      Both groups had a significant and similar improvement in basal and provokable
      obstruction, septal thickness, NYHA functional class, exercise tolerance, peak
      oxygen consumption, and pulmonary artery mean pressure at workload. Significant
      differences, compared with the younger group, were a higher proportion of
      persistent total atrioventricular block (5% v 17%, p = 0.015) and a slight
      decrease in left ventricular ejection fraction (3 (12) v -6 (11)%, p = 0.001) in
      the elderly, despite a trend to a lower induced peak creatine kinase activity
      (596 (339) v 491 (331) U/l, p = 0.051). CONCLUSIONS: Short term results with
      transcoronary ablation of septal hypertrophy suggest that independent of a
      patient's age similar treatment strategies are justified in hypertrophic
      obstructive cardiomyopathy.

PMID- 15145868
TI  - Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic
      resonance in patients with non-diagnostic echocardiography.
AB  - OBJECTIVE: To investigate the role of cardiovascular magnetic resonance (CMR) in
      a series of patients with ECG repolarisation changes and normal echocardiography.
      PATIENTS AND DESIGN: 10 patients with anterolateral T wave inversion for which
      there was no obvious pathological cause who had normal routine echocardiography
      without contrast for the exclusion of hypertrophic cardiomyopathy (HCM) also had
      CMR that was diagnostic of apical HCM. RESULTS: Apical HCM detected by CMR could
      be morphologically severe with wall thickness up to 28 mm, or mild. The extent of
      repolarisation abnormalities did not correlate to the morphological severity.
      CONCLUSIONS: In patients with unexplained repolarisation abnormalities, a normal
      routine echocardiogram without contrast does not exclude apical HCM. Further
      imaging with CMR or contrast echocardiography may be required. The reliance on
      routine echocardiography to exclude apical HCM may have led to underreporting of
      this condition.

PMID- 15145870
TI  - Amino-terminal propeptide of type III procollagen is associated with restrictive
      mitral filling pattern in patients with dilated cardiomyopathy: a possible link
      between diastolic dysfunction and prognosis.
AB  - OBJECTIVE: To analyse the relation between restrictive mitral pattern, amino
      terminal propeptide of type III procollagen (PIIINP), and prognosis in patients
      with dilated cardiomyopathy. DESIGN: Prospective cohort study of 106 patients
      with dilated cardiomyopathy. SETTING: Tertiary care centre. MAIN OUTCOME
      MEASURES: PIIINP concentration, echocardiographic variables, oxygen consumption,
      hospitalisation for heart failure, and cardiac mortality were evaluated in
      patients grouped by the presence of non-restrictive (group 1), reversible (group
      2), and irreversible restrictive mitral pattern (group 3). RESULTS: Groups
      differed regarding left ventricular ejection fraction (group 1, mean (SD) 36
      (6)%, group 2, 29 (8)%, group 3, 25 (6)%; p = 0.0001), left atrial ejection
      fraction (group 1, 0.47 (0.1)%, group 2, 0.43 (0.2)%, group 3, 0.26 (0.1)%; p <
      0.0001), and PIIINP (p = 0.001). Multivariate analysis showed that PIIINP was
      related to mitral pattern (odds ratio 0.8, 95% confidence interval 0.23 to 1.4, p
      = 0.006) independently of left atrial and ventricular ejection fractions. After
      21 months, survival was 88% and 34% (p = 0.0001) in patients with non-restrictive
      and irreversible restrictive mitral patterns, respectively. CONCLUSION: In
      patients with dilated cardiomyopathy, restrictive mitral pattern is associated
      with higher PIIINP and worse prognosis.

PMID- 15145871
TI  - No reflow was caught red handed in a patient with acute anterior myocardial
      infarction undergoing rescue angioplasty.

PMID- 15145872
TI  - Value of echocardiography for diagnosis and prognosis of chronic Chagas disease
      cardiomyopathy without heart failure.
AB  - OBJECTIVES: To establish the usefulness of echocardiography for the clinical
      classification of patients with Chagas disease and to determine the predictors of
      mortality and clinical events. METHODS: 849 patients with chronic Chagas disease
      with a mean follow up of 9.9 years were studied. On admission, ECG, chest
      radiograph, and two dimensional echocardiogram were obtained from all patients.
      Clinical events were defined as new ECG abnormalities, change in clinical status
      resulting in transfer to another group, and death. Morphologically characterised
      segmental lesions were also seen in 12 patients on a second harmonic
      echocardiogram with intravenous contrast agent. Univariate and multivariate
      analysis for clinical events and mortality were performed. SETTING: Community of
      San Martin, Buenos Aires, Argentina. RESULTS: Change in clinical group (68 of 833
      survivors v 15 of 16 who died, p < 0.001), left ventricular systolic dimension
      (mean (SD) 3.06 (0.72) cm v 4.71 (0.90) cm, p < 0.0001), and ejection fraction
      (mean (SD) 0.67 (0.11)% v 0.42 (0.17)%, p < 0.0001) were found to be the only
      predictors of mortality. ECG abnormalities related to the disease (in 220 of 699
      patients with no clinical event v 98 of 150 patients with a clinical event, p <
      0.0001), left ventricular diastolic dimension (mean (SD) 4.88 (0.54) cm v 5.44
      (0.83) cm, p < 0.0001), left ventricular systolic dimension (mean (SD) 2.98
      (0.62) cm v 3.64 (1.03) cm, p < 0.0001), and ejection fraction (mean (SD) 0.68
      (0.10)% v 0.60 (0.16)%, p < 0.0001) were predictors of clinical events. Segmental
      lesions were observed in 211 of 849 patients (25%). Segmental lesions were seen
      in 66 (13%) and systolic dysfunction was seen in four of 505 (0.8%) patients with
      normal ECG. Significant differences were found between the groups of patients
      (group 0: reactive serology and normal ECG and chest radiography without cardiac
      enlargement and no signs of heart failure; group 1: reactive serology and
      abnormal ECG and chest radiography without cardiac enlargement; group 2: reactive
      serology and abnormal ECG and chest radiography with cardiac enlargement and no
      signs of heart failure). CONCLUSION: Echocardiography was useful both to
      characterise and to determine the prognosis of patients with chronic Chagas
      disease without heart failure.

PMID- 15145873
TI  - Aneurysm of the left main coronary artery in Takayasu arteritis.

PMID- 15145874
TI  - Incidence of atrial fibrillation and thromboembolism in a randomised trial of
      atrial versus dual chamber pacing in 177 patients with sick sinus syndrome.
AB  - OBJECTIVE: To analyse the occurrence of atrial fibrillation (AF) and
      thromboembolism in a randomised comparison of rate adaptive single chamber atrial
      pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome
      and normal atrioventricular (AV) conduction, in which left atrial dilatation and
      decreased left ventricular fractional shortening had been observed in the DDDR
      group. METHODS: 177 consecutive patients with sick sinus syndrome (mean (SD) age
      74 (9) years, 104 women) were randomly assigned to treatment with one of three
      pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60)
      (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was
      intention to treat. RESULTS: Mean follow up was 2.9 (1.1) years. AF at one or
      more ambulatory visits was significantly less common in the AAIR group (4 (7.4%)
      v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log
      rank test). The risk of developing AF in the AAIR group compared with the DDDR-s
      group was significantly decreased after adjustment for brady-tachy syndrome in a
      Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to
      0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy
      syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker
      implantation were independent predictors of thromboembolism during follow up
      (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI
      1.2 to 17.9, p = 0.02, respectively). CONCLUSIONS: During a mean follow up of 2.9
      years AAIR was associated with significantly less AF. The beneficial effect of
      AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy
      syndrome was associated with an increased risk of thromboembolism.

PMID- 15145877
TI  - A comparison of coronary artery stenting with angioplasty for isolated stenosis
      of the proximal left anterior descending coronary artery: five year clinical
      follow up.
AB  - BACKGROUND: Stent implantation for isolated stenosis of the proximal left
      anterior descending coronary artery (LAD) with preserved left ventricular
      function has been found to have a better clinical and angiographic outcome at one
      year than balloon angioplasty (PTCA). OBJECTIVE: To establish whether those
      results are maintained at five year follow up. METHODS: Patients were followed at
      least every six months. For those who died during follow up, data were obtained
      from medical records. MAIN OUTCOME MEASURES: Freedom from death, non-fatal
      myocardial infarction, cerebrovascular accident, and repeated target lesion
      revascularisation. Secondary end points were revascularisation in a remote region
      and freedom from angina. RESULTS: Follow up was complete in all patients. At five
      years, the primary end point was reached more often by patients randomised to
      stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence
      interval (CI) 0.13 to 0.69); p = 0.0034). In the PTCA group, 35% of patients
      underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95%
      CI 0.13 to 0.80; p = 0.014). There was a trend towards increased mortality in the
      PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p =
      0.098). No significant differences were found between PTCA and stent groups for
      non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p = 0.46)
      or cerebrovascular accident (2% v 0%). CONCLUSIONS: In patients with isolated
      stenosis of the proximal LAD, a five year clinical follow up confirmed a better
      outcome in those treated with stenting than with PTCA.

PMID- 15145875
TI  - Incidence and electrophysiological characteristics of spontaneous ventricular
      tachyarrhythmias in high risk coronary patients and prophylactic implantation of
      a defibrillator.
AB  - OBJECTIVES: To assess the incidence and electrophysiological characteristics of
      spontaneous ventricular tachyarrhythmias after implantable cardioverter
      defibrillator (ICD) implantation for primary prevention. DESIGN: Prospective
      observational study. PATIENTS: 41 consecutive patients, who fulfilled MADIT
      (multicenter automatic defibrillator implantation trial) I criteria, except for
      suppressibility by procainamide, and who received a prophylactic ICD.
      INTERVENTIONS: Subpectoral implantation of an ICD. MAIN OUTCOME MEASURES:
      Incidence of ventricular tachyarrhythmias and their electrophysiological
      characteristics with respect to timing of the arrhythmia, tachyarrhythmia cycle
      length, mode of termination, and clinical relevance. RESULTS: During a mean (SD)
      follow up of 30 (21) months 18 of 41 (43.9%) patients experienced 142 appropriate
      ICD treatments. The mean (SD) time to first event was 9.6 (15.1) months. One
      patient had ventricular fibrillation (VF), 12 patients ventricular tachycardia
      (VT), and five both VT and VF. The mean (SD) cycle length of monomorphic VT was
      306 (42) ms. Of 142 episodes, 117 (82.3%) were terminated by antitachycardia
      pacing and another 25 (17.6%) by ICD discharges. Cumulative survival of
      hypothetical death, defined as treated VT with a cycle length < 260 ms or VF, was
      83.2% after one year and 78.4% after two years. CONCLUSIONS: Patients with a left
      ventricular ejection fraction < 35%, a history of myocardial infarction, non
      sustained VT, and inducible VT/VF are at high risk of VT/VF early after
      implantation. Therefore, implantation of a tiered treatment defibrillator seems
      to be justified.

PMID- 15145878
TI  - Summary of recommendations on percutaneous coronary intervention for the
      reperfusion of acute ST elevation myocardial infarction.

PMID- 15145881
TI  - Decrease in circulating endothelial progenitor cells in patients with stable
      coronary artery disease.

PMID- 15145882
TI  - Lower 24 hour urinary sodium concentrations are associated with more severe
      symptoms in subjects with vasovagal syncope.

PMID- 15145879
TI  - Cardiovascular response to physical exercise in adult patients after atrial
      correction for transposition of the great arteries assessed with magnetic
      resonance imaging.
AB  - OBJECTIVE: To assess with magnetic resonance imaging (MRI) cardiovascular
      function in response to exercise in patients after atrial correction of
      transposition of the great arteries (TGA). METHODS: Cardiac function at rest and
      during submaximal exercise was assessed with MRI in 27 patients with TGA (mean
      (SD) age 26 (5) years) late (23 (2) years) after atrial correction and in 14
      control participants (25 (5) years old). RESULTS: At rest, only right ventricular
      ejection fraction was significantly lower in patients than in controls (56 (7)% v
      65 (7)%, p < 0.05). In response to exercise, increases in right ventricular end
      diastolic (155 (55) ml to 163 (57) ml, p < 0.05) and right ventricular end
      systolic volumes (70 (34) ml to 75 (36) ml, p < 0.05) were observed in patients.
      Furthermore, right and left ventricular stroke volumes and ejection fraction did
      not increase significantly in patients. Changes in right ventricular ejection
      fraction with exercise correlated with diminished exercise capacity (r = 0.43, p
      < 0.05). CONCLUSIONS: In patients with atrially corrected TGA, MRI showed an
      abnormal response to exercise of both systemic right and left ventricles.
      Exercise MRI provides a tool for close monitoring of cardiovascular function in
      these patients, who are at risk for late death.

PMID- 15145883
TI  - Role of serum cardiac troponin T in the diagnosis of acute rheumatic fever and
      rheumatic carditis.

PMID- 15145885
TI  - Haemodynamic significance of stent lesions compared to native coronary lesions: a
      myocardial perfusion imaging study.

PMID- 15145886
TI  - Mortality caused by acute myocardial infarction in Qatari women.

PMID- 15145887
TI  - Ventricular aneurysm secondary to sarcoid disease.

PMID- 15145888
TI  - A population based study of Ramadan fasting and acute coronary syndromes.

PMID- 15145889
TI  - Right ventricular ischaemia due to right coronary artery stenosis.

PMID- 15145891
TI  - Management of acute coronary syndromes: an update.

PMID- 15145893
TI  - Percutaneous coronary intervention for bifurcation coronary disease.

PMID- 15145892
TI  - Utility of echocardiography in the evaluation of individuals with cardiomyopathy.

PMID- 15145895
TI  - Right ventricular diastolic dysfunction and patent foramen ovale causing profound
      cyanosis.
AB  - A 73 year old woman presented with profound central cyanosis and a history of a
      minor stroke. She had normal heart morphology, normal pulmonary artery pressure,
      and a normal coronary angiography. A patent foramen ovale (PFO) with a massive
      right to left shunt was demonstrated at the atrial level, with normal pulmonary
      venous saturations and PO2 values. This rare, age related case of right
      ventricular diastolic dysfunction in a normotensive patient revealed a generous
      PFO allowing a pronounced right to left shunt.

PMID- 15145896
TI  - Human coronary morphology after beta radiation brachytherapy of in-stent
      restenosis.
AB  - This case report discusses the human coronary morphological findings 18 hours
      after brachytherapy (beta radiation) of an in-stent restenosis. Brachytherapy
      produced aseptic inflammation of the periadventitial connective tissue
      integrating the vasa vasorum in the acute phase. The stent neointima eight months
      after stenting and acutely 18 hours after radiation consisted of the same
      cellular components as human stent neointima of specimen not additionally treated
      with radiation. No evidence of necrosis or excessive fibrotic alterations of the
      arterial vessel wall have been found.

PMID- 15145897
TI  - Failure of intravascular ultrasound to identify the site of recurrent focal
      coronary spasm during stenting.
AB  - Focal coronary spasm is often associated with an area of mural plaque disease.
      This report describes a patient with recurrent severe coronary spasm unresponsive
      to medical treatment. Coronary arteriography and intravascular ultrasound
      identified a candidate area of minor coronary atheromatous disease but ergonovine
      provocation testing showed the spastic coronary segment to be distal to and
      distinct from this area. Coronary stenting of the site identified by ergonovine
      provocation testing was effective in relieving provoked and spontaneous spasm.

PMID- 15145898
TI  - Candida endocarditis with mycotic pulmonary emboli following re-do Rastelli
      operation.
AB  - A case of a 19 year old patient with Candida endocarditis complicated by
      pulmonary infarction and pulmonary mycotic abscesses following replacement of a
      right ventricle to pulmonary artery homograft conduit is presented. Despite
      preceding hospital admissions with probable septic pulmonary emboli, diagnosis
      was made only after massive pulmonary haemorrhage that ultimately proved fatal.
      This case highlights that Candida endocarditis should be considered in patients
      with symptoms and signs compatible with bacterial endocarditis when blood
      cultures are negative, especially in the setting of congenital cardiac
      malformations, and illustrates the high mortality associated with delayed
      diagnosis.

PMID- 15145899
TI  - Incidental finding of a papillary fibroelastoma on the aortic valve in 16 slice
      multi-detector row computed tomography.
AB  - Papillary fibroelastoma (PFE) is a benign, rare, gelatinous tumour derived from
      the endocardium, primarily the cardiac valves, which is usually diagnosed by high
      resolution echocardiography. Although rarely clinically symptomatic, PFEs have a
      potential for coronary ischaemia, systemic embolisation with neurologic symptoms,
      and sometimes valvar dysfunction. There are reports of coronary occlusion and
      even sudden cardiac death due to a ball valve phenomenon on the coronary ostia.
      This report describes the characteristics of a PFE with multidetector 16 slice
      computed tomography and 1.5 Tesla cardiac magnetic resonance imaging.

PMID- 15145900
TI  - Pseudo-pericardial tamponade after perforation of the right coronary artery.
AB  - A case of perforation of the right coronary artery, which was complicated by an
      intramural right ventricular haematoma with pseudo-pericardial tamponade
      resulting in fatal asystole, is presented.

PMID- 15145902
TI  - Cardiovascular risk: a UK priority--it's time to act II.

PMID- 15145903
TI  - Meeting the challenge of cardiovascular care in the new National Health Service.
AB  - The National Service Framework (NSF) established coronary heart disease as a
      priority area for the government and for the National Health Service (NHS). In
      the three and a half years since its launch, good progress has been made and the
      NSF is already delivering real improvements for patients, demonstrated by a near
      25% reduction in the death rate from circulatory diseases. Prescribing of
      cardiovascular drugs for secondary prevention has increased, acute myocardial
      infarction is being treated more promptly, and there is improved access to
      revascularisation procedures. However, there is still a notable class
      differential in cardiovascular deaths. There has been exponential growth in use
      of statins but the drugs are still not being used to optimum effect. Heart
      failure has now been identified as a priority for action.

PMID- 15145904
TI  - Applying the evidence: guidelines in primary care.
AB  - General practice has faced a tremendous workload challenge in meeting the
      National Service Framework targets. For the first time, the new General Medical
      Services (GMS) contract links practice remuneration to diagnosis and management
      of chronic diseases; in particular, it offers practices a significant financial
      incentive to undertake management of cardiovascular disease. However, in order to
      undertake the work and meet the targets, particularly those relating to
      management of blood pressure, serum lipids, and glucose, primary care teams will
      have to approach cardiovascular disease in a highly systematic manner. Much of
      the work is likely to fall upon practice nurses. While many in primary care have
      been reluctant in the past to invest in future health gain, the new GMS contract
      offers a good opportunity to change that way of thinking.

PMID- 15145905
TI  - Engaging patients in managing their cardiovascular health.
AB  - Psychological factors play a major part in the impact, course, and treatment of
      cardiovascular disease. Patients' cognitions and emotions feed into their
      responses to their illness and its treatments and can, for example, affect the
      likelihood of attendance at cardiac rehabilitation programmes. It is important to
      view the rehabilitation process from the perspective of the patient and to
      examine and assess patients' beliefs. Self management and self efficacy need to
      be encouraged. Depression and anxiety are common after myocardial infarction and
      can influence outcome. A patient's mood state should be assessed routinely and
      regularly.

PMID- 15145906
TI  - New evidence in hypertension and hyperlipidaemia.
AB  - The benefits of blood pressure lowering on the risk of cardiovascular disease are
      seen with all commonly used classes of antihypertensive drugs. Although different
      drug classes may have different effects on cause specific outcomes (such as
      myocardial infarction or stroke), no differences are observed between their
      overall effects on combined major cardiovascular end points. The choice of first
      line antihypertensive drug is therefore likely to be of less importance than the
      use of any effective drug, particularly since the majority of patients will need
      two or more agents to achieve blood pressure goals. Recent trials have provided
      good evidence that lowering cholesterol with statins reduces the risk of
      cardiovascular events in "high risk" patients, irrespective of initial
      cholesterol concentrations. The benefits of both blood pressure lowering and
      lipid lowering treatment appear to be proportional to the extent of the reduction
      of blood pressure and lipids achieved.

PMID- 15145907
TI  - Diabetes: preventing coronary heart disease in a high risk group.
AB  - Cardiovascular disease is the major cause of morbidity and mortality in patients
      with type 2 diabetes. Numerous outcome trials have demonstrated clinical benefits
      from effective treatment of individual cardiovascular risk factors in patients
      with diabetes. These trials have provided the basis for current treatment
      guidelines and targets. More recently, multifactorial intervention strategies
      have shown a reduction in both cardiovascular and microvascular events in
      patients with type 2 diabetes. However, full implementation of a truly
      multifactorial strategy into routine practice remains an ideal due to practical
      difficulties of sustained implementation and associated costs. These practical
      issues relating to the treatment of diabetes and its complications are now in a
      greater spotlight due to the growing number of patients requiring treatment.

PMID- 15145908
TI  - Primary prevention of cardiovascular disease: managing hypertension and
      hyperlipidaemia.
AB  - Cardiovascular medicine has a sound evidence base upon which health professionals
      can base their interventions to modify risk among the British public. For primary
      prevention of cardiovascular disease, however, while there is considerable
      evidence on what to do, data are limited on how the evidence should be
      implemented in practice. The challenge will be to learn by experience which
      interventions directed at reducing blood pressure and lipids levels work best in
      different settings. There is a need to structure care to identify individuals who
      are at risk. Current targets are explicit and achievable for both hypertension
      and lipids. Effective treatment is likely to require multiple drug treatment.

PMID- 15145909
TI  - Managing the cost of cardiovascular prevention in primary care.
AB  - Prescribing costs for the prevention of cardiovascular disease are rising
      nationally, particularly in relation to implementation of the National Service
      Framework for coronary heart disease. Prescribing effective treatment that is
      going to benefit the patient's overall management--evidence based medicine--is
      the key to funding drugs for cardiovascular prevention. It is clear that there is
      a lot of waste within the system. If the current waste in prescribing can be
      reduced, it should be possible to fund new developments, not only in
      cardiovascular disease but also in other therapeutic areas.

PMID- 15145901
TI  - Recommendations on percutaneous coronary intervention for the reperfusion of
      acute ST elevation myocardial infarction.
AB  - Little information is currently available from the various societies of
      cardiology on primary percutaneous coronary intervention (PCI) for acute
      myocardial infarction (AMI). Since primary PCI is the main method of reperfusion
      in AMI in many centres, and since of all cardiac emergencies AMI represents the
      most urgent situation for PCI, recommendations based on scientific evidence and
      expert experience would be useful for centres practising primary PCI, or those
      looking to establish a primary PCI programme. To this aim, a task force for
      primary PCI in AMI was formed to develop a set of recommendations to complement
      and assist clinical judgment. This paper represents the product of their
      recommendations.

PMID- 15145910
TI  - Secondary prevention clinics: improving quality of life and outcome.
AB  - General practitioners have been encouraged to target patients with coronary heart
      disease for secondary prevention, but putting this into practice has proven
      challenging. However, there is now evidence of the benefits from nurse led
      clinics in primary care. Randomised trials have shown that such clinics can lead
      to improvement in both medical and lifestyle components of secondary prevention.
      This has in turn been associated with improved quality of life and a reduction in
      mortality. Benefits are conditional on several factors: in particular, risk
      factors are only reduced if clinic attendance is accompanied by appropriate
      prescribing, and improvements in risk factors are only sustained if the clinics
      are continued.

PMID- 15145911
TI  - Treating to hypertension targets.
AB  - Control of blood pressure levels in hypertensive patients often fails to meet the
      targets suggested by the British Hypertension Society (BHS) guidelines. The
      optimal treatment target for non-diabetic patients is < or = 140/85 mm Hg. Data
      from the health survey for England show that in 1998 only 8% of men and 11% of
      women had blood pressure controlled to < 140/90 mm Hg. The Anglo-Scandinavian
      cardiac outcomes trial (ASCOT) data show that 87% of non-diabetic patients in the
      St Mary's Centre are currently treated to below 140/90 mm Hg. These differences
      can be explained by strict protocol adherence, a focus on cardiovascular disease,
      longer consultation times and punctual appointments, reinforcement of non
      pharmacological advice, and blood pressure readings taken in line with BHS
      guidelines. Some of these points might be translated into the more challenging
      setting of primary care.

PMID- 15145912
TI  - Helping patients to improve self management of diabetes.
AB  - Research suggests that people with diabetes are poorly compliant with dietary and
      exercise recommendations, and that primary non-compliance with medication is
      common. Local research has shown that patients' beliefs about diabetes suggest
      little understanding of the seriousness of the disease in terms of increased
      mortality. Portsmouth Primary Care Trust, in collaboration with Portsmouth
      Hospitals NHS Trust, is developing a range of structured self management
      programmes to assist in helping people be clearer about how they can make changes
      that will reduce their risk of diabetes complications and cardiovascular disease.
      These programmes are delivered to groups of patients, rather than on a single
      patient basis.

PMID- 15145914
TI  - Age-related enhancement of fatigue resistance is evident in men during both
      isometric and dynamic tasks.
AB  - It has been suggested that the effects of old age on the ability to resist
      fatigue may be task dependent. To test one aspect of this hypothesis, we compared
      the neuromuscular responses of nine young (26 +/- 4 yr, mean +/- SD) and nine
      older (72 +/- 4 yr) healthy, relatively sedentary men to intermittent isometric
      (3 min, 5 s contract/5 s rest) and dynamic (90 at 90 degrees /s) maximum
      voluntary contractions (MVC) of the ankle dorsiflexor muscles. To assess the
      mechanisms of fatigue (defined as the ratio of postexercise MVC to preexercise
      MVC), we also measured isometric central activation ratios (CAR), tetanic torque,
      contractile properties, and compound muscle action potentials before and
      immediately after exercise. Because dynamic contractions are more neurally
      complex and metabolically demanding than isometric contractions, we expected an
      age-related fatigue resistance observed during isometric exercise to be absent
      during dynamic exercise. In contrast, older men (O) fatigued less than young (Y)
      during both isometric (O = 0.77 +/- 0.07, Y = 0.66 +/- 0.02, mean +/- SE; P <
      0.01) and dynamic (O = 0.45 +/- 0.07, Y = 0.27 +/- 0.02; P = 0.04) contractions
      (ratio of postexercise to preexercise MVC), with no evidence of peripheral
      activation failure in either group. We observed no obvious limitations in central
      activation in either group, as assessed using isometric CAR methods, after both
      isometric and dynamic contractions. Preexercise half-time of tetanic torque
      relaxation, which was longer in O compared with Y, was linearly associated with
      fatigue resistance during both protocols (r = 0.62 and 0.66, P < or = 0.004, n =
      18). These results suggest that relative fatigue resistance is enhanced in older
      adults during both isometric and isokinetic contractions and that age-related
      changes in fatigue may be due largely to differences within the muscle itself.

PMID- 15145915
TI  - Effect of prior multiple-sprint exercise on pulmonary O2 uptake kinetics
      following the onset of perimaximal exercise.
AB  - We hypothesized that the metabolic acidosis resulting from the performance of
      multiple-sprint exercise would enhance muscle perfusion and result in a speeding
      of pulmonary oxygen uptake (VO2)kinetics during subsequent perimaximal-intensity
      constant work rate exercise, if O2 availability represented a limitation to VO2
      kinetics in the control (i.e., no prior exercise) condition. On two occasions,
      seven healthy subjects completed two bouts of exhaustive cycle exercise at a work
      rate corresponding to approximately 105% of the predetermined Vo2 peak, separated
      by 3 x 30-s maximal sprint cycling and 15-min recovery (MAX1 and MAX2). Blood
      lactate concentration (means +/- SD: MAX1: 1.3 +/- 0.4 mM vs. MAX2: 7.7 +/- 0.9
      mM; P < 0.01) was significantly greater immediately before, and heart rate was
      significantly greater both before and during, perimaximal exercise when it was
      preceded by multiple-sprint exercise. Near-infrared spectroscopy also indicated
      that muscle blood volume and oxygenation were enhanced when perimaximal exercise
      was preceded by multiple-sprint exercise. However, the time constant describing
      the primary component (i.e., phase II) increase in VO2 was not significantly
      different between the two conditions (MAX1: 33.8 +/- 5.5 s vs. MAX2: 33.2 +/- 7.7
      s). Rather, the asymptotic "gain" of the primary Vo2 response was significantly
      increased by the performance of prior sprint exercise (MAX1: 8.1 +/- 0.9 ml.min(
      1).W(-1) vs. MAX2: 9.0 +/- 0.7 ml.min(-1).W(-1); P < 0.05), such that VO2 was
      projecting to a higher "steady-state" amplitude with the same time constant.
      These data suggest that priming exercise, which apparently increases muscle O2
      availability, does not influence the time constant of the primary-component VO2
      response but does increase the amplitude to which VO2 may rise following the
      onset of perimaximal-intensity cycle exercise.

PMID- 15145916
TI  - Relative roles of heredity and physical activity in adolescence and adulthood on
      blood pressure.
AB  - Part of the association between physical activity and low blood pressure (BP) may
      be a consequence of genetic selection. We investigated the association of genetic
      factors and physical activity in adolescence and adulthood with BP. BP was
      measured with a Finapres device in 71 monozygotic and 104 dizygotic male twin
      pairs using no antihypertensive medication. Subjects' mean age was 50.4 yr (range
      40-72 yr). Subjects were interviewed about their lifetime exercise and other
      health habits. Exercise was classified as aerobic, power, or other, and these
      were further divided into adolescence (12-20 yr of age), the previous year, and
      lifetime. Genetic modeling was conducted to estimate genetic and environmental
      components of variance of systolic and diastolic BP. Aerobic exercise in
      adolescence and high-intensity aerobic exercise throughout the lifetime were
      associated with low diastolic BP in adulthood. Of the variance in diastolic BP,
      genetic factors accounted for 35% and aerobic exercise in adolescence for 5%. For
      systolic BP, genetic factors accounted for 39% of the variance. In turn, genetic
      factors accounted for 44% of the variance in aerobic exercise in adolescence. The
      genetic factors in part accounting for the variance in diastolic BP and those in
      part accounting for variance in aerobic exercise in adolescence were correlated.
      The association between aerobic exercise in adolescence and low diastolic BP in
      adulthood is a new finding, as is the observation that the factors partly share
      the same genes.

PMID- 15145917
TI  - Effects of tourniquet-induced ischemia on the release of proopiomelanocortin
      derivatives determined in peripheral blood plasma.
AB  - Proopiomelanocortin (POMC) is expressed in pituitary, central nervous system, and
      in a few peripheral tissues. This study addresses the hypothesis that metabolic
      stressors, such as acidosis, may induce the release of POMC derivatives into the
      cardiovascular system not only from the pituitary but also from other sites of
      POMC expression. In our study, we investigated the liberation of POMC derivatives
      from peripheral tissues under a state of acidosis achieved by tourniquet-induced
      ischemia, alteration of lactate concentration, and base excess. In eight patients
      undergoing knee arthroplasty under spinal anesthesia, catheters were inserted
      into the femoral vein proximally to thigh tourniquet location. Blood was drawn
      from these catheters 5 min before and 40 s, 5 min, and 10 min after tourniquet
      deflation to measure plasma concentrations of N-acetyl-beta-endorphin
      immunoreactive material (IRM), beta-endorphin IRM, authentic beta-endorphin,
      adrenocorticotropin, lactate, pH, and base excess. In five of eight patients, we
      found a significant increase of beta-endorphin IRM levels 40 s after tourniquet
      deflation compared with predeflation levels; 5 and 10 min after tourniquet
      deflation, the beta-endorphin IRM levels were below the detection limit. Thus
      beta-endorphin IRM was released from ischemic limb tissues into the
      cardiovascular system. Only a small part of the determined beta-endorphin IRM
      corresponded to authentic beta-endorphin. Forty seconds after tourniquet
      deflation, the beta-endorphin IRM concentration correlated with base excess (r <
      0.71; P < 0.05); no significant correlations were found with pH or lactate
      levels. Thus it was shown here for the first time that ischemic stress may induce
      the release of beta-endorphin IRM from nonpituitary tissues.

PMID- 15145918
TI  - Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline
      receptor-mediated hypotension in female rats.
AB  - We have recently shown that estrogen negatively modulates the hypotensive effect
      of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates
      the cardiovascular autonomic control in this interaction. The present study
      investigated whether this effect of estrogen involves interaction with alpha2-
      and/or I1-receptors. Changes evoked by a single intraperitoneal injection of
      rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and
      alpha2-receptor agonists, respectively, in blood pressure, hemodynamic
      variability, and locomotor activity were assessed in radiotelemetered sham
      operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12
      wk estrogen replacement. Three time domain indexes of hemodynamic variability
      were employed: the standard deviation of mean arterial pressure as a measure of
      blood pressure variability and the standard deviation of beat-to-beat intervals
      (SDRR) and the root mean square of successive differences in R-wave-to-R-wave
      intervals as measures of heart rate variability. In sham-operated rats,
      rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least
      5 h and was associated with reductions in standard deviation of mean arterial
      pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced
      the hypotensive response to alpha-methyldopa, in contrast to no effect on
      rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats
      was paralleled with further reduction in SDRR and a reduced locomotor activity.
      Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12
      wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha
      methyldopa to sham-operated levels. These findings suggest that estrogen
      downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a
      role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.

PMID- 15145919
TI  - Role of UCP3 in state 4 respiration during contractile activity-induced
      mitochondrial biogenesis.
AB  - In an effort to better characterize uncoupling protein-3 (UCP3) function in
      skeletal muscle, we assessed basal UCP3 protein content in rat intermyofibrillar
      (IMF) and subsarcolemmal (SS) mitochondrial subfractions in conjunction with
      measurements of state 4 respiration. UCP3 content was 1.3-fold (P < 0.05) greater
      in IMF compared with SS mitochondria. State 4 respiration was 2.6-fold greater (P
      < 0.05) in the IMF subfraction than in SS mitochondria. GDP attenuated state 4
      respiration by approximately 40% (P < 0.05) in both subfractions. The UCP3
      activator oleic acid (OA) significantly increased state 4 respiration in IMF
      mitochondria only. We used chronic electrical stimulation (3 h/day for 7 days) to
      investigate the relationship between changes in UCP3 protein expression and
      alterations in state 4 respiration during contractile activity-induced
      mitochondrial biogenesis. UCP3 content was increased by 1.9- and 2.3-fold in IMF
      and SS mitochondria, respectively, which exceeded the concurrent 40% (P < 0.05)
      increase in cytochrome-c oxidase activity. Chronic contractile activity increased
      state 4 respiration by 1.4-fold (P < 0.05) in IMF mitochondria, but no effect was
      observed in the SS subfraction. The uncoupling function of UCP3 accounted for 50
      57% of the OA-induced increase in state 4 respiration in IMF mitochondria, which
      was independent of the induced twofold difference in UCP3 content due to chronic
      contractile activity. Thus modifications in UCP3 function are more important than
      changes in UCP3 expression in modifying state 4 respiration. This effect is
      evident in IMF but not SS mitochondria. We conclude that UCP3 at physiological
      concentrations accounts for a significant portion of state 4 respiration in both
      IMF and SS mitochondria, with the contribution being greater in the IMF
      subfraction. In addition, the contradiction between human and rat training
      studies with respect to UCP3 protein expression may partly be explained by the
      greater than twofold difference in mitochondrial UCP3 content between rat and
      human skeletal muscle.

PMID- 15145920
TI  - Cyclical elongation regulates contractile responses of isolated airways.
AB  - Bronchoconstrictor responses are quantitatively different when they are evoked
      under static conditions and during or after periods of deep inspiration. In vivo,
      deep inspirations produce bronchodilation and protect the lung from subsequent
      bronchoconstriction (termed bronchoprotection). These effects may be due in part
      to dynamic stretch on airways produced by cyclical expansion of airway diameter.
      However, airways also lengthen cyclically during breathing. The effects of
      cyclical airway elongation on evoked bronchoconstriction have not been examined.
      This study recorded evoked contractions of pig bronchial segments 1) at different
      airway lengths, 2) after a period of cyclical lengthening in relaxed airways, and
      3) during cyclical lengthening in pretoned airways. Airway segments were mounted
      in organ baths and bathed in Krebs solution luminally and on the adventitia.
      Airways were cyclically lengthened by 5-30% of their deflated length at 0.5-2 Hz
      for 5 min. Contractions were evoked by electrical field stimulation or carbachol
      and were recorded under isovolumic conditions. Under static conditions, there was
      a blunt relationship between length and response to electrical field stimulation.
      After a period of airway length cycling, electrical field stimulation-induced
      contractions were increased. In airways pretoned with carbachol, cyclical
      lengthening produced a transient bronchodilation and a sustained increase in
      contraction. Contractile responses were not blocked by indomethacin. The results
      show that isolated airways respond actively to dynamic changes in length. Our
      results indicate that cyclical lengthening of airways could contribute to lung
      function in vivo but does not appear to account for the phenomenon of
      bronchoprotection.

PMID- 15145921
TI  - Gender and ethnic differences in urinary stress hormones: the population-based
      Chicago Health, Aging, and Social Relations Study.
AB  - Gender and ethnic disparities in cardiovascular disease and mortality have
      spurred interest in the epidemiology of stress hormone production. Greater
      disease burden among men and blacks raises the possibility of gender and ethnic
      differences in stress hormone production. The purpose of this study was to
      determine whether urinary stress hormones were higher among men and blacks in a
      population-based sample. Urinary hormone analysis permits a time-integrated
      assessment of the stress response system. However, differences in collection and
      standardization strategies have led to inconsistent findings. Subjects were an
      ethnically diverse population-based sample of 229 men and women aged 50-67 yr who
      provided an overnight urine specimen. Urine concentration was standardized using
      a traditional creatinine-based approach as well as a new method that accounts for
      muscle mass. With the use of creatinine standardization, no gender or ethnic
      differences were noted in epinephrine or cortisol production. Norepinephrine
      levels were higher among women compared with men (P = 0.001), however. After
      accounting for muscle mass, we found that both epinephrine (P = 0.018) and
      norepinephrine (P = 0.033) levels were higher among men compared with women. No
      significant differences in cortisol production were found by gender or ethnicity.
      The consistency of these results with previous studies of 24-h urine samples
      suggests muscle mass should be accounted for when comparing overnight urinary
      hormone values across gender and ethnicity.

PMID- 15145922
TI  - Effects of long-term captopril and L-arginine treatment on ventilation and blood
      pressure in obese male SHHF rats.
AB  - We investigated the effects of captopril (Cap) and L-arginine (Arg) on
      hypertension and cardiopulmonary function. Our hypothesis was that Cap therapy or
      Arg will improve cardiopulmonary risk factors for hypertension and
      hypoventilation in the obese spontaneously hypertensive heart failure rat, which
      is characterized by hypertension, obesity, and disorders of lipid and
      carbohydrate metabolism. For the first study, one group of rats received Cap in
      drinking water, and a second group received deionized water (DI). For the second
      study, rats were further subdivided. Some Cap-treated rats continued on this
      treatment, and the other half were now given DI to determine whether there would
      be residual effects of Cap treatment. A subgroup of rats who had received DI was
      then given Arg, whereas the rest remained on DI. In the first study, Cap-treated
      rats exhibited decreases in systolic and diastolic blood pressures, frequency of
      breathing, and minute ventilation, but ventilatory control was maintained. In
      contrast, blood pressures and relative ventilation to metabolism were higher in
      the DI-treated group. Removal of Cap increased blood pressure and decreased tidal
      volume while these rats maintained frequency. Although Arg-treated rats did not
      exhibit a decrease of blood pressure, ventilation was maintained in this group by
      preserving tidal volume. Thus Cap and Arg affected ventilation through different
      mechanisms independent of blood pressure.

PMID- 15145923
TI  - Effects of moderate exercise and oat beta-glucan on lung tumor metastases and
      macrophage antitumor cytotoxicity.
AB  - Both moderate exercise and the soluble fiber beta-glucan can have beneficial
      effects on the initiation and growth of tumors, but the data are limited, and
      there is no information on their combined effects. This study tested the
      independent and combined effects of short-term moderate-exercise training and the
      soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor
      cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to
      one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con
      ObetaG. ObetaG was fed in the drinking water for 10 days before tumor
      administration and death. Exercise consisted of treadmill running (1 h/day) for 6
      days. After rest or exercise on the last day of training, syngeneic B16 melanoma
      cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per
      group). Lungs were removed 14 days later, and tumor foci were counted. Additional
      mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for
      cytotoxicity against the same mouse tumor cell line at various effector-to-target
      ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased
      macrophage cytotoxicity. However, there were no differences in lung tumor foci
      and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG.
      These data suggest that, although not additive in their effects, both short-term
      moderate-exercise training and consumption of the soluble ObetaG can decrease the
      metatastic spread of injected B16 melanoma cells, and these effects may be
      mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

PMID- 15145924
TI  - Autonomic control of the cardiovascular system during acclimatization to high
      altitude: effects of sildenafil.
AB  - Both acute hypoxia and sildenafil may influence autonomic control through
      transient cardiovascular effects. In a double-blind study, we investigated
      whether sildenalfil (Sil) could interfere with cardiovascular effects of hypoxia.
      Twelve healthy men [placebo (Pla) n = 6; Sil, n = 6] were exposed to an altitude
      of 4,350 m during 6 days. Treatment was continuously administered from 6 to 8 h
      after arrival at altitude (3 x 40 mg/day). The autonomic control on the heart was
      assessed by heart rate variability (HRV) during sleep at sea level (SL) and
      between day 1-2 and day 5-6 in hypoxia. Arterial pressure (AP) and total
      peripheral resistances (TPR) were obtained during daytime. There was no
      statistical difference between groups in HRV, AP, and TPR throughout the study.
      Hypoxia induced a decrease in R-R interval and an increase in AP in both groups.
      Low frequency-to-high frequency ratio increased at day 1-2 (Pla, P = 0.04; Sil, P
      = 0.02) and day 5-6 (Pla and Sil, P = 0.04) vs. SL, whereas normalized high
      frequency power decreased only in Pla (P = 0.04, day 1-2 vs. SL). Normalized low
      frequency power increased at high altitude (Pla and Sil, P = 0.04, day 5-6 vs.
      SL). TPR decreased at day 2 in Pla (P = 0.02) and tended to normalize at day 6 (P
      = 0.07, day 6 vs. day 2). Acute hypoxia induced a decrease in parasympathetic and
      increase in sympathetic tone, which tended to be reversed with acclimatization.
      Sil had no deleterious effects on the cardiovascular response to high-altitude
      exposure and its control by the autonomic nervous system.

PMID- 15145926
TI  - Interactive effects of habitual physical activity and calcium intake on bone
      density in boys and girls.
AB  - The purpose of this study was to assess the interactive effects of habitual
      physical activity (total and vigorous intensity) and calcium intake on bone
      mineral content (BMC) in prepubertal boys and girls. Seventy-six children, aged 8
      11 yr, wore accelerometers for up to 7 days to assess activity. Calcium intake
      was estimated by a 4-day weighted food diary. BMC and areal density (bone mineral
      density) were measured at the total body, proximal femur, and femoral neck by
      using dual-energy X-ray absorptiometry. Moderated regression analyses were used
      to assess the contributions of physical activity (total and vigorous) and calcium
      intake to BMC, residualized for bone area and body mass. Interactive effects of
      vigorous activity (> or =6 metabolic equivalents) and calcium intake were found
      at the total body in boys (b = 2.90 x 10(-3)) and in girls (b = 6.58 x 10(-3))
      and at the proximal femur (b = 9.87 x 10(-5)) and femoral neck (b = 2.29 x 10(
      5); where b is the regression coefficient from final equation) in boys only;
      residualized BMC was high only if both vigorous activity and calcium intake were
      high. There were no interactive effects of total activity and calcium intake.
      This study provides evidence for synergistic action of habitual vigorous activity
      and calcium intake on bone mass in children. Recommendations for optimizing bone
      mass should reflect this synergism.

PMID- 15145925
TI  - Gender differences in insulin action after a single bout of exercise.
AB  - Effects of a single exercise bout on insulin action were compared in men (n = 10)
      and women (n = 10). On an exercise day, subjects cycled for 90 min at 85% lactate
      threshold, whereas on a rest (control) day, they remained semirecumbent. The
      period of exercise, or rest, was followed by a 3-h hyperinsulinemic-euglycemic
      clamp (30 mU.m(-2).min(-1)) and indirect calorimetry. Glucose kinetics were
      measured isotopically by using an infusion of [6,6-2H2]glucose. Glucose infusion
      rate (GIR) during the clamp on the rest day was not different between the
      genders. However, GIR on the exercise day was significantly lower in men compared
      with women (P = 0.01). This was mainly due to a significantly lower glucose rate
      of disappearance in men compared with women (P = 0.05), whereas no differences
      were observed in the endogenous glucose rate of appearance. Nonprotein
      respiratory quotient (NPRQ) increased significantly during the clamp from
      preclamp measurements in men and women on the rest day (P < 0.01). Exercise
      abolished the increase in NPRQ seen during the clamp on the rest day and tended
      to decrease NPRQ in men. Our results indicate the following: 1) exercise
      abolishes the usual increase in NPRQ observed during a hyperinsulinemic
      euglycemic clamp in both genders, 2) men exhibit relatively lower whole body
      insulin action in the 3-4 h after exercise compared with women, and 3) gender
      differences in insulin action may be explained by a lower glucose rate of
      disappearance in the men after acute exercise. Together, these data imply gender
      differences in insulin action postexercise exist in peripheral tissues and not in
      liver.

PMID- 15145927
TI  - Effects of 10-day confinement on the immune system and psychological aspects in
      humans.
AB  - We investigated the changes in percentages of leukocyte subpopulations, natural
      killer (NK) cells, CD69-expressing lymphocytes, and psychological aspects in 10
      subjects who participated in a 10-day confinement study. Suppression of
      lymphocyte proliferative reaction and changes in leukocyte distribution are known
      to occur in space. These responses are similar to those induced by psychological
      stress. Ground-based confinement studies are suitable for validating the effects
      of stress arising only due to confinement. Two groups, consisting of five male
      subjects (ages 20-27 yr, mean 22.8 yr) each, participated in a 10-day confinement
      study. Blood samples were taken once before, three times during, and once after
      the confinement and activated with an anti-CD2 agonistic antibody cocktail. The
      percentages of leukocyte subpopulations, NK (CD45(+)CD56+) cells, and activated
      lymphocytes (CD45(+)CD69+) were measured by flow cytometric assay. The face scale
      test was used to measure psychological aspects. The percentage of CD69+
      lymphocytes decreased during the period of confinement. This was mostly caused by
      changes in the ratio between NK and non-NK lymphocytes. The face scale showed
      that the subjects' moods improved toward the postconfinement period. Consistent
      with the face scale, the percentages of innate immune cells, such as NK cells and
      granulocytes, increased during the postconfinement period. We concluded that the
      changes in the distribution of immune cells caused by stress plays an important
      role in suppression of proliferative reactivity. The observed physiological
      reactions were specific to the confined environment, and the stress caused by
      confinement plays a role in the immune changes observed in space.

PMID- 15145928
TI  - Lens major intrinsic protein (MIP)/aquaporin 0 expression in rat lens epithelia
      explants requires fibroblast growth factor-induced ERK and JNK signaling.
AB  - Lens major intrinsic protein (MIP), exclusive to the vertebrate lens, otherwise
      known as MIP26 and Aquaporin 0, is abundantly expressed as a lens fiber membrane
      protein. Although relatively less efficient compared with other aquaporins, MIP
      is suggested to function as a water channel, as an adhesion molecule, and is
      required for lens transparency. Because MIP is specifically expressed in lens
      fiber cells, we investigated in this study the activation of Mip expression after
      triggering differentiation of rat lens epithelia explants by fibroblast growth
      factor (FGF)-2. Here, we show that Mip expression in the lens cells is regulated
      by FGF-2. Using Real time PCR we demonstrate that endogenous Mip levels in the
      explants were up-regulated upon FGF-2 stimulation, in a concentration-dependent
      manner. Up-regulation of Mip at the transcriptional level was simultaneous with
      the activation of the FGF down-stream signaling components, ERK1/2 and JNK.
      Specific inhibitors, UO126 for ERK1/2 and SP600125 for JNK, abrogated Mip
      expression in response to FGF-2 in the explants. This inhibition pattern was
      recapitulated in reporter assays for transfection of the rat lens epithelia
      explants, driven by the Mip promoter (-1648/+44). Our studies show that ERK1/2
      and JNK signaling pathways are required for Mip expression in lens epithelia
      explants induced to differentiate by FGF-2.

PMID- 15145929
TI  - Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor
      protein with hsp90 and its nuclear translocation.
AB  - Pifithrin-alpha (PFTalpha) was originally thought to be a specific inhibitor of
      signaling by the tumor suppressor protein p53. However, the laboratory that
      discovered pifithrin recently reported that the compound also inhibits heat shock
      and glucocorticoid receptor (GR) signaling, and they suggested that PFTalpha
      targets a factor common to all three signal transduction pathways, such as the
      hsp90/hsp70-based chaperone machinery (Komarova, E. A., Neznanov, N., Komarov, P.
      G., Chernov, M. V., Wang, K., and Gudkov, A. V. (2003) J. Biol. Chem. 278, 15465
      15468). Because it is important for the mechanistic study of this machinery to
      identify unique inhibitors of chaperone action, we have examined the effect of
      PFTalpha on transcriptional activation, the hsp90 heterocomplex assembly, and
      hsp90-dependent nuclear translocation for both p53 and the GR. At concentrations
      where PFTalpha blocks p53-mediated induction of p21/Waf-1 in human embryonic
      kidney cells, we observed no inhibition of GR-mediated induction of a
      chloramphenicol acetyl transferase reporter in LMCAT cells. PFTalpha did,
      however, cause a left shift in the dexamethasone dose response curve by
      increasing intracellular dexamethasone concentration, apparently by competing for
      dexamethasone efflux from the cell. The assembly of p53 or GR heterocomplexes
      with hsp90 and immunophilins was not affected by PFTalpha either in vivo or in
      vitro and did not affect the nuclear translocation of either transcription
      factor. Thus, we conclude that PFTalpha does not inhibit GR-mediated induction or
      the function of the chaperone machinery, and, as originally thought, it may
      specifically inhibit p53 signaling by acting at a stage after p53 translocation
      to the nucleus.

PMID- 15145930
TI  - Glycerophosphoinositol, a novel phosphate source whose transport is regulated by
      multiple factors in Saccharomyces cerevisiae.
AB  - Git1p mediates the transport of the phospholipid metabolite,
      glycerophosphoinositol, into Saccharomyces cerevisiae. We report that phosphate
      limitation and inositol limitation affect GIT1 expression and Git1p transport
      activity via distinct mechanisms that involve multiple transcription factors.
      GIT1 transcript levels and Git1p activity are greater in cells starved for
      phosphate, with or without inositol limitation, than in cells only limited for
      inositol. Furthermore, the kinetics of GIT1 transcript accumulation and Git1p
      activity upon transfer of cells to phosphate starvation media are different from
      those obtained upon transfer of cells to inositol-free media. Pho2p and Pho4p are
      required for GIT1 expression and for Git1p transport activity under all growth
      conditions tested. In contrast, Ino2p and Ino4p are required for full GIT1
      expression when inositol is limiting, with or without phosphate limitation, but
      not when only phosphate is limiting. Greatly reduced transport activity was
      detected in ino2Delta and ino4Delta cells under all growth conditions. A 300-base
      pair region of the GIT1 promoter containing potential Pho4p binding sites was
      shown to be required for full GIT1 expression. Git1p appears to act as a H(+)
      symporter, and neither inositol nor phosphate effectively compete with
      glycerophosphoinositol for transport by Git1p. Glycerophosphoinositol was shown
      previously to support the growth of an inositol auxotroph. Remarkably, we now
      report that glycerophosphoinositol can act as the sole source of phosphate for
      the cell, providing functional relevance for the regulation of Git1p transport
      activity by phosphate.

PMID- 15145931
TI  - A maternal Ahr null genotype sensitizes embryos to chemical teratogenesis.
AB  - The aryl hydrocarbon receptor (encoded by the Ahr locus) is a ligand-activated
      transcription factor that mediates the toxicology and teratology of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (dioxin). In an effort to understand the role of the
      maternal compartment in dioxin teratology, we designed a breeding strategy that
      allowed us to compare the teratogenic response in embryos from Ahr(-/-) (null)
      and Ahr(+/+) (wild-type) dams. Using this strategy, we demonstrate that embryos
      from the Ahr(-/-) dams are 5-fold more sensitive to dioxin-induced cleft palate
      and hydronephrosis as compared with embryos from an Ahr(+/+) dam. Moreover, this
      increased teratogenic sensitivity extends beyond dioxin, because embryos from
      Ahr(-/-) dams exhibited a 9-fold increase in their sensitivity to the fetotoxic
      effects of the glucocorticoid, dexamethasone. In searching for an explanation for
      this increased sensitivity, we found that more dioxin and dexamethasone reached
      the embryos from Ahr(-/-) dams as compared with embryos from Ahr(+/+) dams. We
      propose that increased deposition of teratogens/fetotoxicants to the embryonic
      compartment is the result of porto-systemic shunting and/or blocked P4501A
      induction in Ahr(-/-) dams. In addition to demonstrating the importance of
      maternal AHR in teratogenesis, these data may have implications that reach beyond
      the mechanism of action of dioxin. In this regard, the Ahr(-/-) mouse may provide
      a system that allows pharmacological agents and toxicants to be more easily
      studied in a model where first pass clearance is a significant obstacle.

PMID- 15145932
TI  - Nucleic acid is a novel ligand for innate, immune pattern recognition collectins
      surfactant proteins A and D and mannose-binding lectin.
AB  - Collectins are a family of innate immune proteins that contain fibrillar collagen
      like regions and globular carbohydrate recognition domains (CRDs). The CRDs of
      these proteins recognize various microbial surface-specific carbohydrate
      patterns, particularly hexoses. We hypothesized that collectins, such as
      pulmonary surfactant proteins (SPs) SP-A and SP-D and serum protein mannose
      binding lectin, could recognize nucleic acids, pentose-based anionic phosphate
      polymers. Here we show that collectins bind DNA from a variety of origins,
      including bacteria, mice, and synthetic oligonucleotides. Pentoses, such as
      arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and
      mannan, one of the well-studied hexose ligands for SP-D, and biologically
      relevant d-forms of the pentoses are better competitors than the l-forms. In
      addition, DNA and RNA polymer-related compounds, such as nucleotide diphosphates
      and triphosphates, also inhibit the carbohydrate binding ability of SP-D, or
      approximately 60 kDa trimeric recombinant fragments of SP-D that are composed of
      the alpha-helical coiled-coil neck region and three CRDs (SP-D(n/CRD)) or SP
      D(n/CRD) with eight GXY repeats (SPD(GXY)(8)(n/CRD)). Direct binding and
      competition studies suggest that collectins bind nucleic acid via their CRDs as
      well as by their collagen-like regions, and that SP-D binds DNA more effectively
      than do SP-A and mannose-binding lectin at physiological salt conditions.
      Furthermore, the SP-D(GXY)(8)(n/CRD) fragments co-localize with DNA, and the
      protein competes the interaction between propidium iodide, a DNA-binding dye, and
      apoptotic cells. In conclusion, we show that collectins are a new class of
      proteins that bind free DNA and the DNA present on apoptotic cells by both their
      globular CRDs and collagen-like regions. Collectins may therefore play an
      important role in decreasing the inflammation caused by DNA in lungs and other
      tissues.

PMID- 15145934
TI  - Roles of stem cell factor/c-Kit and effects of Glivec/STI571 in human uveal
      melanoma cell tumorigenesis.
AB  - The B-Raf(V599E)-mediated constitutive activation of ERK1/2 is involved in
      establishing the transformed phenotype of some uveal melanoma cells (Calipel, A.,
      Lefevre, G., Pouponnot, C., Mouriaux, F., Eychene, A., and Mascarelli, F. (2003)
      J. Biol. Chem. 278, 42409-42418). We have shown that stem cell factor (SCF) is
      involved in the proliferation of normal uveal melanocytes and that c-Kit is
      expressed in 75% of primary uveal melanomas. This suggests that the acquisition
      of autonomous growth during melanoma progression may involve the SCF/c-Kit axis.
      We used six human uveal melanoma tumor-derived cell lines and normal uveal
      melanocytes to characterize the SCF/c-Kit system and to assess its specific role
      in transformation. We investigated the possible roles of activating mutations in
      c-KIT, the overexpression of this gene, and ligand-dependent c-Kit overactivation
      in uveal melanoma cell tumorigenesis. Four cell lines (92.1, SP6.5, Mel270, and
      TP31) expressed both SCF and c-Kit, and none harbored the c-KIT mutations in
      exons 9, 11, 13, and 17 that have been shown to induce SCF-independent c-Kit
      activation. Melanoma cell proliferation was strongly inhibited by small
      interfering RNA-mediated depletion of c-Kit in these cells, despite the presence
      of (V599E)B-Raf in SP6.5 and TP31 cells. We characterized the signaling pathways
      involved in SCF/c-Kit-mediated cell growth and survival in normal and tumoral
      melanocytes and found that constitutive ERK1/2 activation played a key role in
      both the SCF/c-Kit autocrine loop and the gain of function of (V599E)B-Raf for
      melanoma cell proliferation and transformation. We also provide the first
      evidence that Glivec/STI571, a c-Kit tyrosine kinase inhibitor, could be used to
      treat uveal melanomas.

PMID- 15145933
TI  - Overexpressed GM1 suppresses nerve growth factor (NGF) signals by modulating the
      intracellular localization of NGF receptors and membrane fluidity in PC12 cells.
AB  - Ganglioside GM1 has been considered to have a neurotrophic factor-like activity.
      To analyze the effects of endogenously generated GM1, the rat pheochromocytoma
      cell line PC12 was transfected with the GM1/GD1b/GA1 synthase gene and showed
      increased expression levels of GM1. To our surprise, GM1+-transfectant cells
      (GM1+ cells) showed no neurite formation after stimulation with nerve growth
      factor (NGF). Autophosphorylation of NGF receptor TrkA and activation of ERK1/2
      after NGF treatment were scarcely detected in GM1+ cells. Binding of 125I-NGF to
      PC12 cells was almost equivalent between GM1+ cells and controls. However, dimer
      formation of TrkA upon NGF treatment was markedly suppressed in GM1+ cells in
      both cross-linking analysis with Bis(sulfosuccinimidyl)suberate 3 and 125I-NGF
      binding assay. The sucrose density gradient fractionation of the cell lysate
      revealed that TrkA primarily located in the lipid raft fraction moved to the non
      raft fraction in GM1+ cells. p75NTR and Ras also moved from the raft to non-raft
      fraction in GM1+ cells, whereas flotillin and GM1 persistently resided in the
      lipid raft. TrkA kinase activity was differentially regulated when GM1 was added
      to the kinase assay system in vitro, suggesting suppressive/enhancing effects of
      GM1 on NGF signals based on the concentration. Measurement of fluorescence
      recovery after photobleaching revealed that the membrane fluidity was reduced in
      GM1+ cells. These results suggested that overexpressed GM1 suppresses the
      differentiation signals mediated by NGF/TrkA by modulating the properties of the
      lipid raft and the intracellular localization of NGF receptors and relevant
      signaling molecules.

PMID- 15145936
TI  - Influence of DNA structure on DNA polymerase beta active site function: extension
      of mutagenic DNA intermediates.
AB  - In the ternary substrate complex of DNA polymerase (pol) beta, the nascent base
      pair (templating and incoming nucleotides) is sandwiched between the duplex DNA
      terminus and polymerase. To probe molecular interactions in the dNTP-binding
      pocket, we analyzed the kinetic behavior of wild-type pol beta on modified DNA
      substrates that alter the structure of the DNA terminus and represent mutagenic
      intermediates. The DNA substrates were modified to 1) alter the sequence of the
      duplex terminus (matched and mismatched), 2) introduce abasic sites near the
      nascent base pair, and 3) insert extra bases in the primer or template strands to
      mimic frameshift intermediates. The results indicate that the nucleotide
      insertion efficiency (k(cat)/K(m), dGTP-dC) is highly dependent on the sequence
      identity of the matched (i.e. Watson-Crick base pair) DNA terminus
      (template/primer, G/C approximately A/T > T/A approximately C/G). Mismatches at
      the primer terminus strongly diminish correct nucleotide insertion efficiency but
      do not affect DNA binding affinity. Transition intermediates are generally
      extended more easily than transversions. Most mismatched primer termini decrease
      the rate of insertion and binding affinity of the incoming nucleotide. In
      contrast, the loss of catalytic efficiency with homopurine mismatches at the
      duplex DNA terminus is entirely due to the inability to insert the incoming
      nucleotide, since K(d)((dGTP)) is not affected. Abasic sites and extra
      nucleotides in and around the duplex terminus decrease catalytic efficiency and
      are more detrimental to the nascent base pair binding pocket when situated in the
      primer strand than the equivalent position in the template strand.

PMID- 15145935
TI  - A novel in vivo role for osteoprotegerin ligand in activation of monocyte
      effector function and inflammatory response.
AB  - Osteoprotegerin Ligand (OPGL) is a member of the tumor necrosis factor ligand
      superfamily and has been shown to be involved in interactions between T cells and
      dendritic cells. Its role in monocyte effector function, however, has not been
      defined. In the present study a role for OPGL in activating monocytes/macrophages
      has been characterized. OPGL was found to up-regulate receptor activator of NF
      kappaB (RANK) receptor expression on monocytes, regulate their effector function
      by inducing cytokine and chemokine secretion, activate antigen presentation
      through up-regulation of co-stimulatory molecule expression, and promote
      survival. This activation is mediated through the MAPK pathway as evidenced by
      activation of p38 and p42/44 MAPK and up-regulation of BCL-XL protein levels. A
      physiological role for OPGL in monocyte activation and effector function was
      tested in a model of lipopolysaccharide-induced endotoxic shock. Administration
      of receptor activator of NF-kappaB (RANK)-Fc to block OPGL activity in vivo was
      able to protect mice from death induced by sepsis, indicating a hitherto
      undescribed role for OPGL in monocyte function and in mediating inflammatory
      response. This was further tested in an animal model of inflammation-mediated
      arthritis. Treatment with RANK-Fc significantly ameliorated disease development
      and attenuated bone destruction. Thus, our study strongly suggests that
      administration of receptor fusion proteins to specifically block OPGL activity in
      vivo may result in blocking development of monocyte/macrophage-mediated diseases.

PMID- 15145937
TI  - Hepatocyte resistance to oxidative stress is dependent on protein kinase C
      mediated down-regulation of c-Jun/AP-1.
AB  - The prevention of injury from reactive oxygen species is critical for cellular
      resistance to many death stimuli. Resistance to death from the superoxide
      generator menadione in the hepatocyte cell line RALA255-10G is dependent on down
      regulation of the c-Jun N-terminal kinase (JNK)/AP-1 signaling pathway by
      extracellular signal-regulated kinase 1/2 (ERK1/2). Because protein kinase C
      (PKC) regulates both oxidant stress and JNK signaling, the ability of PKC to
      modulate hepatocyte death from menadione through effects on AP-1 was examined.
      PKC inhibition with Ro-31-8425 or bisindolylmaleimide I sensitized this cell line
      to death from menadione. Menadione treatment led to activation of PKCmicro, or
      protein kinase D (PKD), but not PKCalpha/beta, PKCzeta/lambda, or PKCdelta/.
      Menadione induced phosphorylation of PKD at Ser-744/748, but not Ser-916, and
      translocation of PKD to the nucleus. PKC inhibition blocked menadione-induced
      phosphorylation of PKD, and expression of a constitutively active PKD prevented
      death from Ro-31-8425/menadione. PKC inhibition led to a sustained overactivation
      of JNK and c-Jun in response to menadione as determined by in vitro kinase assay
      and immunoblotting for the phosphorylated forms of both proteins. Cell death from
      PKC inhibition and menadione treatment resulted from c-Jun activation, since
      death was blocked by adenoviral expression of the c-Jun dominant negative TAM67.
      PKC and ERK1/2 independently down-regulated JNK/c-Jun, since inhibition of either
      kinase failed to affect activation of the other kinase, and simultaneous
      inhibition of both pathways caused additive JNK/c-Jun activation and cell death.
      Resistance to death from superoxide therefore requires both PKC/PKD and ERK1/2
      activation in order to down-regulate proapoptotic JNK/c-Jun signaling.

PMID- 15145938
TI  - Reduced G protein-coupled signaling efficiency in retinal rod outer segments in
      response to n-3 fatty acid deficiency.
AB  - The fatty acid (FA) docosahexaenoic acid (DHA, 22: 6n-3) is highly enriched in
      membrane phospholipids of the central nervous system and retina. Loss of DHA
      because of n-3 FA deficiency leads to suboptimal function in learning, memory,
      olfactory-based discrimination, spatial learning, and visual acuity. G protein
      coupled receptor (GPCR) signal transduction is a common signaling motif in these
      neuronal pathways. Here we investigated the effect of n-3 FA deficiency on GPCR
      signaling in retinal rod outer segment (ROS) membranes isolated from rats raised
      on n-3-adequate or -deficient diets. ROS membranes of second generation n-3 FA
      deficient rats had approximately 80% less DHA than n-3-adequate rats. DHA was
      replaced by docosapentaenoic acid (22:5n-6), an n-6 FA. This replacement
      correlated with desensitization of visual signaling in n-3 FA-deficient ROS, as
      evidenced by reduced rhodopsin activation, rhodopsin-transducin (G(t)) coupling,
      cGMP phosphodiesterase activity, and slower formation of metarhodopsin II (MII)
      and the MII-G(t) complex relative to n-3 FA-adequate ROS. ROS membranes from n-3
      FA-deficient rats exhibited a higher degree of phospholipid acyl chain order
      relative to n-3 FA-adequate rats. These findings reported here provide an
      explanation for the reduced amplitude and delayed response of the
      electroretinogram a-wave observed in n-3 FA deficiency in rodents and nonhuman
      primates. Because members of the GPCR family are widespread in signaling pathways
      in the nervous system, the effect of reduced GPCR signaling due to the loss of
      membrane DHA may serve as an explanation for the suboptimal neural signaling
      observed in n-3 FA deficiency.

PMID- 15145939
TI  - The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and
      serves as a positive regulator of transcriptional activation by STAT6.
AB  - Transcriptional activation by signal transducer and activator of transcription 6
      (STAT6) has been shown to require the direct interaction not only with co
      activators such as p300 and cAMP-responsive element-binding protein-binding
      protein (CBP) but also with nuclear co-activator 1, a member of the p160/steroid
      receptor co-activator family. Among the p160/steroid receptor co-activators, only
      p/CIP (nuclear co-activator 3) has been shown to be up-regulated by interleukin
      (IL)-4 in B cells through a STAT-6-dependent mechanism using Gene-Chip analysis.
      In this study, we have investigated the function of p/CIP in the transcriptional
      activation by STAT6. We found that p/CIP indirectly interacted with STAT6 via
      p300, and overexpression of the CBP-interacting domain of p/CIP (p/CIP(947-1084))
      prevented the interaction of p/CIP with STAT6 by blocking the binding of p/CIP to
      p300. Whereas expression of p/CIP(947-1084) resulted in a marked reduction of
      STAT6-mediated transactivation, overexpression of wild type p/CIP resulted in
      significant enhancement of it. In addition, p/CIP(947-1084) markedly reduced CD23
      expression on B cells stimulated with IL-4, whereas overexpression of wild type
      p/CIP enhanced it. Chromatin immunoprecipitations demonstrate that IL-4 increases
      the interaction of p/CIP with the murine immunoglobulin heavy chain germ line
      epsilon promoter in B cells. These results suggest that p/CIP positively
      regulates STAT6 transcriptional activation through formation of a STAT6,
      p300/CBP, and p/CIP complex.

PMID- 15145940
TI  - Critical amino acid residues in transmembrane domain 1 of the human organic anion
      transporter hOAT1.
AB  - Human organic anion transporter 1 (hOAT1) belongs to a superfamily of organic
      anion transporters, which play critical roles in the body disposition of
      clinically important drugs, including anti-human immunodeficiency virus
      therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti
      inflammatories. Previously we suggested that the predicted transmembrane domain 1
      (TM1) of hOAT1 might be important for its function. In the present study, we
      examined the role of each residue within TM1 of hOAT1 in substrate recognition
      and transport. Alanine scanning was used to construct mutants of hOAT1, and the
      uptake of model substrate para-aminohippurate was studied in COS-7 cells
      expressing the mutant transporters. This approach led to the discovery of two
      critical amino acid residues, Leu-30 and Thr-36. A substitution of Leu-30 or Thr
      36 with alanine resulted in a complete loss of transport activities. We then
      further characterized Leu-30 and Thr-36 by mutagenizing these residues to amino
      acids with different physicochemical properties. Leu-30 was replaced with amino
      acids with varying sizes of side chains, including glycine, valine, and
      isoleucine. We showed that progressively smaller side chains at position 30
      increasingly impaired hOAT1 function mainly because of the impaired surface
      expression of the transporter. Thr-36, another critical amino acid in TM1, was
      replaced by serine and cysteine. Similar to the substitution of Thr-36 by
      alanine, substitution by serine and cysteine at this position abolished transport
      activity without affecting the surface expression of the transporter. The fact
      that Thr-36 cannot be substituted with serine and that the side chains of
      alanine, serine, and cysteine are smaller than that of threonine by a methyl
      group indicate that both the methyl group and the hydroxyl group of Thr-36 could
      be critical for hOAT1 activity. Together we conclude that Leu-30 and Thr-36 play
      distinct roles in hOAT1 function. Leu-30 is important in targeting the
      transporter to the plasma membrane. In contrast, Thr-36 is critical for substrate
      recognition. The present study provided the first molecular evidence that
      transmembrane domain 1 is a critical determinant of hOAT1 function and may
      provide important insights into the structure-function relationships of the
      organic anion transporter family.

PMID- 15145942
TI  - COX23, a homologue of COX17, is required for cytochrome oxidase assembly.
AB  - Deletion of reading frame YHR116W of the Saccharomyces cerevisiae nuclear genome
      elicits a respiratory deficiency. The encoded product, here named Cox23p, is
      shown to be required for the expression of cytochrome oxidase. Cox23p is
      homologous to Cox17p, a water-soluble copper protein previously implicated in the
      maturation of the Cu(A) center of cytochrome oxidase. The respiratory defect of a
      cox23 null mutant is rescued by high concentrations of copper in the medium but
      only when the mutant harbors COX17 on a high copy plasmid. Overexpression of
      Cox17p by itself is not a sufficient condition to rescue the mutant phenotype.
      Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and
      in the postmitochondrial supernatant fraction, the latter consisting
      predominantly of cytosolic proteins. Because Cox23p and Cox17p are not part of a
      complex, the requirement of both for cytochrome oxidase assembly suggests that
      they function in a common pathway with Cox17p acting downstream of Cox23p.

PMID- 15145941
TI  - Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated
      hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region.
AB  - F-box proteins, components of SCF ubiquitin-ligase complexes, are believed to be
      responsible for substrate recognition and recruitment in SCF-mediated
      proteolysis. F-box proteins that have been identified to function in the SCF
      complexes to date mostly have substrate-binding motifs, such as WD repeats or
      leucine-rich repeats in their C termini. However, many F-box proteins lack
      recognizable substrate-binding modules; whether they can function in the SCF
      complexes remains unclear. We show here that Fbx7, an F-box protein without WD
      repeats and leucine-rich repeats, is required for the proteasome-mediated
      proteolysis of the hepatoma up-regulated protein (HURP). Depletion of Fbx7 by
      small interfering RNA leads to depression of HURP ubiquitination and accumulation
      of HURP abundance. In the SCF(Fbx7) complex, Fbx7 recruits HURP through its C
      terminal proline-rich region in a Cdk1-cyclin B-phosphorylation dependent manner.
      Mutation of the multiple Cdk1-cyclin B phosphorylation sites on HURP or the
      proline-rich region of Fbx7 abolishes the association between Fbx7 and HURP.
      Thus, Fbx7 is a functional adaptor of the SCF complex with a proline-rich region
      as the substrate-binding module. In addition to Fbx7, data base analyses reveal
      two putative mammalian proline-rich region-containing F-box proteins, KIAA1783
      and RIKEN cDNA 2410015K21. Taken together, these findings further expound the
      diverse substrate-recognition abilities of the SCF complexes.

PMID- 15145943
TI  - Extracellular Zn2+ activates epithelial Na+ channels by eliminating Na+ self
      inhibition.
AB  - Inhibition of epithelial Na(+) channel (ENaC) activity by high concentrations of
      extracellular Na(+) is referred to as Na(+) self-inhibition. We investigated the
      effects of external Zn(2+) on whole cell Na(+) currents and on the Na(+) self
      inhibition response in Xenopus oocytes expressing mouse alphabetagamma ENaC.
      Na(+) self-inhibition was examined by analyzing inward current decay from a peak
      current to a steady-state current following a fast switching of a low Na(+) (1
      mm) bath solution to a high Na(+) (110 mm) solution. Our results indicate that
      external Zn(2+) rapidly and reversibly activates ENaC in a dose-dependent manner
      with an estimated EC(50) of 2 microm. External Zn(2+) in the high Na(+) bath also
      prevents or reverses Na(+) self-inhibition with similar affinity. Zn(2+)
      activation is dependent on extracellular Na(+) concentration and is absent in
      ENaCs containing gammaH239 mutations that eliminate Na(+) self-inhibition and in
      alphaS580Cbetagamma following covalent modification by a sulfhydryl-reactive
      reagent that locks the channels in a fully open state. In contrast, external
      Ni(2+) inhibition of ENaC currents appears to be additive to Na(+) self
      inhibition when Ni(2+) is present in the high Na(+) bath. Pretreatment of oocytes
      with Ni(2+) in a low Na(+) bath also prevents the current decay following a
      switch to a high Na(+) bath but rendered the currents below the control steady
      state level measured in the absence of Ni(2+) pretreatment. Our results suggest
      that external Zn(2+) activates ENaC by relieving the channel from Na(+) self
      inhibition, and that external Ni(2+) mimics or masks Na(+) self-inhibition.

PMID- 15145944
TI  - Preferential Cu2+ coordination by His96 and His111 induces beta-sheet formation
      in the unstructured amyloidogenic region of the prion protein.
AB  - The prion protein (PrP) is a Cu(2+) binding cell surface glycoprotein that can
      misfold into a beta-sheet-rich conformation to cause prion diseases. The majority
      of copper binding studies have concentrated on the octarepeat region of PrP.
      However, using a range of spectroscopic techniques, we show that copper binds
      preferentially to an unstructured region of PrP between residues 90 and 115,
      outside of the octarepeat domain. Comparison of recombinant PrP with PrP-(91-115)
      indicates that this prion fragment is a good model for Cu(2+) binding to the full
      length protein. In contrast to previous reports we show that Cu(2+) binds to this
      region of PrP with a nanomolar dissociation constant. NMR and EPR spectroscopy
      indicate a square-planar or square-pyramidal Cu(2+) coordination utilizing
      histidine residues. Studies with PrP analogues show that the high affinity site
      requires both His(96) and His(111) as Cu(2+) ligands, rather than a complex
      centered on His(96) as has been previously suggested. Our circular dichroism
      studies indicate a loss of irregular structure on copper coordination with an
      increase in beta-sheet conformation. It has been shown that this unstructured
      region, between residues 90 and 120, is vital for prion propagation and different
      strains of prion disease have been linked with copper binding. The role of Cu(2+)
      in prion misfolding and disease must now be re-evaluated in the light of these
      findings.

PMID- 15145945
TI  - The short stature homeodomain protein SHOX induces cellular growth arrest and
      apoptosis and is expressed in human growth plate chondrocytes.
AB  - Mutations in the homeobox gene SHOX cause growth retardation and the skeletal
      abnormalities associated with Leri-Weill, Langer, and Turner syndromes. Little is
      known about the mechanism underlying these SHOX-related inherited disorders of
      bone formation. Here we demonstrate that SHOX expression in osteogenic stable
      cell lines, primary oral fibroblasts, and primary chondrocytes leads to cell
      cycle arrest and apoptosis. These events are associated with alterations in the
      expression of several cellular genes, including pRB, p53, and the cyclin kinase
      inhibitors p21(Cip1) and p27(Kip1). A SHOX mutant, such as seen in Leri-Weill
      syndrome patients, does not display these activities of the wild type protein. We
      have also shown that endogenous SHOX is mainly expressed in
      hypertrophic/apoptotic chondrocytes of the growth plate, strongly suggesting that
      the protein plays a direct role in regulating the differentiation of these cells.
      This study provides the first insight into the biological function of SHOX as
      regulator of cellular proliferation and viability and relates these cellular
      events to the phenotypic consequences of SHOX deficiency.

PMID- 15145946
TI  - Novel functional interaction between the plasma membrane Ca2+ pump 4b and the
      proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1).
AB  - Plasma membrane calmodulin-dependent calcium ATPases (PMCAs) are enzymatic
      systems implicated in the extrusion of calcium from the cell. We and others have
      previously identified molecular interactions between the cytoplasmic COOH
      terminal end of PMCA and PDZ domain-containing proteins. These interactions
      suggested a new role for PMCA as a modulator of signal transduction pathways. The
      existence of other intracellular regions in the PMCA molecule prompted us to
      investigate the possible participation of other domains in interactions with
      different partner proteins. A two-hybrid screen of a human fetal heart cDNA
      library, using the region 652-840 of human PMCA4b (located in the catalytic,
      second intracellular loop) as bait, revealed a novel interaction between PMCA4b
      and the tumor suppressor RASSF1, a Ras effector protein involved in H-Ras
      mediated apoptosis. Immunofluorescence co-localization, immunoprecipitation, and
      glutathione S-transferase pull-down experiments performed in mammalian cells
      provided further confirmation of the physical interaction between the two
      proteins. The interaction domain has been narrowed down to region 74-123 of
      RASSF1C (144-193 in RASSF1A) and 652-748 of human PMCA4b. The functionality of
      this interaction was demonstrated by the inhibition of the epidermal growth
      factor-dependent activation of the Erk pathway when PMCA4b and RASSF1 were co
      expressed. This inhibition was abolished by blocking PMCA/RASSSF1 association
      with an excess of a green fluorescent protein fusion protein containing the
      region 50-123 of RASSF1C. This work describes a novel protein-protein interaction
      involving a domain of PMCA other than the COOH terminus. It suggests a function
      for PMCA4b as an organizer of macromolecular protein complexes, where PMCA4b
      could recruit diverse proteins through interaction with different domains.
      Furthermore, the functional association with RASSF1 indicates a role for PMCA4b
      in the modulation of Ras-mediated signaling.

PMID- 15145947
TI  - Identification of an amino acid residue in the protein kinase C C1b domain
      crucial for its localization to the Golgi network.
AB  - Protein kinase C (PKC) isoforms have been reported to be targeted to the Golgi
      complex via their C1 domains. We have shown recently that the regulatory domain
      of PKC induces apoptosis in neuroblastoma cells and that this effect is
      correlated to Golgi localization via the C1b domain. This study was designed to
      identify specific residues in the C1 domains that mediate Golgi localization. We
      demonstrate that the isolated C1b domains from PKCalpha, -delta, -epsilon, -eta,
      and - are targeted to the Golgi complex, whereas the corresponding C1a domains
      localize throughout the cell. Sequence alignment showed that amino acid residues
      corresponding to Glu-246 and Met-267 in PKC are conserved among C1b but absent
      from C1a domains. Mutation of Met-267, but not of Glu-246, to glycine abolished
      the Golgi localization of the isolated C1b domain and the regulatory domain of
      PKC. The mutated PKC regulatory domain constructs lacking Golgi localization were
      unable to induce apoptosis, suggesting a direct correlation between Golgi
      localization and apoptotic activity of PKC regulatory domain. Mutation of
      analogous residues in the C1b domain of PKCepsilon abrogated its Golgi
      localization, demonstrating that this effect is not restricted to one PKC
      isoform. The abolished Golgi localization did not affect neurite induction by
      PKCepsilon. However, the PKCepsilon mutant did not relocate to the Golgi network
      in response to ceramide and ceramide did not suppress the neurite-inducing
      capacity of the protein. Thus, the specific mutations in the C1b domain influence
      both the localization and function of full-length PKCepsilon.

PMID- 15145949
TI  - EphA receptors direct the differentiation of mammalian neural precursor cells
      through a mitogen-activated protein kinase-dependent pathway.
AB  - Ephrins are cell surface-associated ligands for Eph receptor tyrosine kinases and
      are implicated in repulsive axon guidance and cell migration. EphA2, 3, and 4
      receptors and one of their cognate ligands, ephrin-A2, are expressed by cells in
      the subventricular zone and ganglionic eminence of the embryonic day 14.5
      telencephalon and by neural precursor cells in vitro. Activation of EphA
      receptors in dissociated neural precursor cells in vitro facilitates the
      commitment to neuronal fates. The majority of ephrin-A1-induced neurons is
      immunoreactive for tyrosine hydroxylase. Blocking the signal by the extracellular
      domain of EphA in forebrain slices results in a decrease in neurogenesis.
      Extracellular signal-regulated kinase is activated by the ligand binding to EphA
      receptors and is involved in the neurogenesis through EphA receptors. Rap1, but
      not Ras, is activated in response to ephrin-A1. Our results identify EphA
      receptors as positive regulators of the mitogen-activated protein kinase pathway
      that exerts neurogenesis of neural precursor cells from the developing central
      nervous system.

PMID- 15145948
TI  - Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake
      of acetylated low density lipoproteins by macrophages stimulated with
      lipopolysaccharide.
AB  - Scavenger receptor expressed by endothelial cells I (SREC-I) is a novel endocytic
      receptor for acetylated low density lipoprotein (LDL). Here we show that SREC-I
      is expressed in a wide variety of tissues, including macrophages and aortas.
      Lipopolysaccharide (LPS) robustly stimulated the expression of SREC-I in
      macrophages. In an initial attempt to clarify the role of SREC-I in the uptake of
      modified lipoproteins as well as in the development of atherosclerosis, we
      generated mice with a targeted disruption of the SREC-I gene by homologous
      recombination in embryonic stem cells. To exclude the overwhelming effect of the
      type A scavenger receptor (SR-A) on the uptake of Ac-LDL, we further generated
      mice lacking both SR-A and SREC-I (SR-A(-/-);SREC-I(-/-)) by cross-breeding and
      compared the uptake and degradation of Ac-LDL in the isolated macrophages. The
      contribution of SR-A and SREC-I to the overall degradation of Ac-LDL was 85 and
      5%, respectively, in a non-stimulated condition. LPS increased the uptake and
      degradation of Ac-LDL by 1.8-fold. In this condition, the contribution of SR-A
      and SREC-I to the overall degradation of Ac-LDL was 90 and 6%, respectively. LPS
      increased the absolute contribution of SR-A and SREC-I by 1.9- and 2.3-fold,
      respectively. On the other hand, LPS decreased the absolute contribution of other
      pathways by 31%. Consistently, LPS did not increase the expression of other
      members of the scavenger receptor family such as CD36. In conclusion, SREC-I
      serves as a major endocytic receptor for Ac-LDL in LPS-stimulated macrophages
      lacking SR-A, suggesting that it has a key role in the development of
      atherosclerosis in concert with SR-A.

PMID- 15145950
TI  - Effect of pH on the stability and structure of yeast hexokinase A. Acidic amino
      acid residues in the cleft region are critical for the opening and the closing of
      the structure.
AB  - pH and salts have a marked effect on the stability, structure, and function of
      many globular proteins due to their ability to influence the electrostatic
      interactions. In this work, calorimetry, CD, and fluorescence studies have been
      carried out to understand the pH-dependent conformational changes of the two
      domain protein yeast hexokinase A. In conjunction with the crystal structural
      data available, the present results have enabled the complete characterization
      and analysis of the pH-dependent conformational changes of the enzyme that have
      strong implications in understanding its structure-function relationship. The
      calorimetric profiles show a single thermal transition in the acidic pH range,
      whereas two independent transitions were observed in the alkaline pH range,
      suggesting the structural merger of the domains at the acidic pH. Comparison of
      the thermal transitions at pH 8.5 studied by different techniques suggests that
      the first transition corresponds to the smaller domain, and the second transition
      corresponds to the larger domain. The acid-denatured state of hexokinase A has
      high secondary structure content with little or no tertiary interactions and
      binds to the hydrophobic dye 8-anilinonaphthalene-1-sulfonic acid, suggesting
      that it is a molten globule-like state, whereas the alkali-denatured state is
      less structured than the acid-denatured state but more structured than the urea
      denatured state, suggestive of a premolten globule-like state. Structural
      analysis using the published hexokinase B structure as well as the hexokinase A
      structure with the revised amino acid sequence in conjunction with the results
      obtained by us suggests that the ionization state of the acidic residues at the
      active site could regulate domain movements that are responsible for the opening
      and the closure of the cleft between the two domains and in turn affect the
      structure and function of the enzyme.

PMID- 15145951
TI  - Efficient incorporation of eukaryotic initiation factor 1 into the multifactor
      complex is critical for formation of functional ribosomal preinitiation complexes
      in vivo.
AB  - Eukaryotic initiation factor 1 (eIF1) is a low molecular weight factor critical
      for stringent AUG selection in eukaryotic translation. It is recruited to the 43
      S complex in the multifactor complex (MFC) with eIF2, eIF3, and eIF5 via multiple
      interactions with the MFC constituents. Here we show that FLAG epitope tagging of
      eIF1 at either terminus abolishes its in vitro interactions with eIF5 and
      eIF2beta but not that with eIF3c. Nevertheless, both forms of FLAG-eIF1 fail to
      bind eIF3 and are incorporated into the 43 S complex inefficiently in vivo. C
      terminal FLAG tagging of eIF1 is lethal; overexpression of C-terminal FLAG-eIF1
      severely impedes 43 S complex formation and derepresses GCN4 translation due to
      limiting of eIF2.GTP.Met-tRNA(i)(Met) ternary complex binding to the ribosome.
      Furthermore, N-terminal FLAG-eIF1 overexpression reduces eIF2 binding to the
      ribosome and moderately derepresses GCN4 translation. Our results provide the
      first in vivo evidence that eIF1 plays an important role in promoting 43 S
      complex formation as a core of factor interactions. We propose that the
      coordinated recruitment of eIF1 to the 40 S ribosome in the MFC is critical for
      the production of functional 40 S preinitiation complex.

PMID- 15145952
TI  - Structural basis of the substrate-specific two-step catalysis of long chain fatty
      acyl-CoA synthetase dimer.
AB  - Long chain fatty acyl-CoA synthetases are responsible for fatty acid degradation
      as well as physiological regulation of cellular functions via the production of
      long chain fatty acyl-CoA esters. We report the first crystal structures of long
      chain fatty acyl-CoA synthetase homodimer (LC-FACS) from Thermus thermophilus HB8
      (ttLC-FACS), including complexes with the ATP analogue adenosine 5'-(beta,gamma
      imido) triphosphate (AMP-PNP) and myristoyl-AMP. ttLC-FACS is a member of the
      adenylate forming enzyme superfamily that catalyzes the ATP-dependent acylation
      of fatty acid in a two-step reaction. The first reaction step was shown to
      propagate in AMP-PNP complex crystals soaked with myristate solution. Myristoyl
      AMP was identified as the intermediate. The AMP-PNP and the myristoyl-AMP complex
      structures show an identical closed conformation of the small C-terminal domains,
      whereas the uncomplexed form shows a variety of open conformations. Upon ATP
      binding, the fatty acid-binding tunnel gated by an aromatic residue opens to the
      ATP-binding site. The gated fatty acid-binding tunnel appears only to allow one
      way movement of the fatty acid during overall catalysis. The protein incorporates
      a hydrophobic branch from the fatty acid-binding tunnel that is responsible for
      substrate specificity. Based on these high resolution crystal structures, we
      propose a unidirectional Bi Uni Uni Bi Ping-Pong mechanism for the two-step
      acylation by ttLC-FACS.

PMID- 15145953
TI  - Proteolytic conversion of STAT3alpha to STAT3gamma in human neutrophils: role of
      granule-derived serine proteases.
AB  - Four isoforms (alpha, beta, gamma, and delta) have been identified for signal
      transducer and activator of transcription 3 (STAT3). It has been reported that
      STAT3gamma, which is derived from STAT3alpha by limited proteolysis during
      granulocytic differentiation, is a major STAT3 isoform expressed in human
      neutrophils. We confirmed that STAT3gamma was a major STAT3 isoform detected in
      human neutrophil lysates prepared with the conventional lysis buffer. The enzymes
      capable of converting STAT3alpha to STAT3gamma in vitro were localized in
      neutrophil granule fraction and were released into the medium upon ionomycin
      stimulation. The enzyme activity was strongly inhibited by phenylmethylsulfonyl
      fluoride, CuSO(4), and ONO-5046 (a specific inhibitor of neutrophil elastase),
      but not by aprotinin, leupeptin, benzamidine, and EDTA. STAT3gamma was
      effectively generated in vitro from STAT3alpha by limited proteolysis with human
      neutrophil elastase or proteinase 3 but not cathepsin G. The converting activity
      in neutrophil lysates was reduced by immunodepletion of elastase but not
      proteinase 3. Unexpectedly, STAT3gamma was undetected in the lysates of
      neutrophil-derived cytoplasts, which lack granules, and the cytosol fraction
      prepared by nitrogen cavitation. The STAT3 isoform detected in these preparations
      was primarily STAT3alpha. STAT3gamma was also undetected in the lysates of PMSF
      pretreated neutrophils and was markedly decreased in the lysates of ionomycin
      pretreated neutrophils. These findings indicate that, in contrast to the previous
      reports, STAT3alpha, but not STAT3gamma, is primarily expressed in human
      neutrophils, and STAT3gamma is rapidly generated from STAT3alpha by limited
      proteolysis with granule-derived serine proteases during preparation of
      neutrophil lysates with the conventional lysis buffer.

PMID- 15145955
TI  - Enhancement by effectors and substrate nucleotides of R1-R2 interactions in
      Escherichia coli class Ia ribonucleotide reductase.
AB  - Ribonucleotide reductases are a family of essential enzymes that catalyze the
      reduction of ribonucleotides to their corresponding deoxyribonucleotides and
      provide cells with precursors for DNA synthesis. The different classes of
      ribonucleotide reductase are distinguished based on quaternary structures and
      enzyme activation mechanisms, but the components harboring the active site region
      in each class are evolutionarily related. With a few exceptions, ribonucleotide
      reductases are allosterically regulated by nucleoside triphosphates (ATP and
      dNTPs). We have used the surface plasmon resonance technique to study how
      allosteric effects govern the strength of quaternary interactions in the class Ia
      ribonucleotide reductase from Escherichia coli, which like all class I enzymes
      has a tetrameric alpha(2) beta(2) structure. The component alpha(2)called R1
      harbors the active site and two types of binding sites for allosteric effector
      nucleotides, whereas the beta(2) component called R2 harbors the tyrosyl radical
      necessary for catalysis. Our results show that only the known allosteric effector
      nucleotides, but not non-interacting nucleotides, promote a specific interaction
      between R1 and R2. Interestingly, the presence of substrate together with
      allosteric effector nucleotide strengthens the complex 2-3 times with a similar
      free energy change as the mutual allosteric effects of substrate and effector
      nucleotide binding to protein R1 in solution experiments. The dual allosteric
      effects of dATP as positive allosteric effector at low concentrations and as
      negative allosteric effector at high concentrations coincided with an almost 100
      fold stronger R1-R2 interaction. Based on the experimental setup, we propose that
      the inhibition of enzyme activity in the E. coli class Ia enzyme occurs in a
      tight 1:1 complex of R1 and R2. Most intriguingly, we also discovered that
      thioredoxin, one of the physiological reductants of ribonucleotide reductases,
      enhances the R1-R2 interaction 4-fold.

PMID- 15145954
TI  - Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes
      revealed using global transcriptional profiling.
AB  - Identification of tumor necrosis factor-alpha (TNF alpha) as the key agent in
      inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and
      psoriasis, led to TNF alpha-targeting therapies, which, although avoiding many of
      the side-effects of previous drugs, nonetheless causes other side-effects,
      including secondary infections and cancer. By controlling gene expression, TNF
      alpha orchestrates the cutaneous responses to environmental damage and
      inflammation. To define TNF alpha action in epidermis, we compared the
      transcriptional profiles of normal human keratinocytes untreated and treated with
      TNF alpha for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found
      that TNF alpha regulates not only immune and inflammatory responses but also
      tissue remodeling, cell motility, cell cycle, and apoptosis. Specifically, TNF
      alpha regulates innate immunity and inflammation by inducing a characteristic
      large set of chemokines, including newly identified TNF alpha targets, that
      attract neutrophils, macrophages, and skin-specific memory T-cells. This
      implicates TNF alpha in the pathogenesis of psoriasis, fixed drug eruption,
      atopic and allergic contact dermatitis. TNF alpha promotes tissue repair by
      inducing basement membrane components and collagen-degrading proteases.
      Unexpectedly, TNF alpha induces actin cytoskeleton regulators and integrins,
      enhancing keratinocyte motility and attachment, effects not previously associated
      with TNF alpha. Also unanticipated was the influence of TNF alpha upon
      keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes.
      Therefore, TNF alpha initiates not only the initiation of inflammation and
      responses to injury, but also the subsequent epidermal repair. The results
      provide new insights into the harmful and beneficial TNF alpha effects and define
      the mechanisms and genes that achieve these outcomes, both of which are important
      for TNF alpha-targeted therapies.

PMID- 15145956
TI  - Glucose regulates interleukin-8 production in aortic endothelial cells through
      activation of the p38 mitogen-activated protein kinase pathway in diabetes.
AB  - We have shown that chronic elevated glucose (25 mm) increases monocyte adhesion
      to human aortic endothelial cells (EC). This increased adhesion is mediated
      primarily through induction of interleukin (IL)-8 via activation of the
      transcription factor AP-1 (Srinivasan, S., Yeh, M., Danziger, E. C., Hatley, M.
      E., Riggan, A. E., Leitinger, N., Berliner, J. A., and Hedrick, C. C. (2003)
      Circ. Res. 92, 371-377). In the current study, we identified the elements in the
      AP-1 transcriptional complex that are activated by glucose. These elements
      include c-Jun, c-Fos, and Fra-1. AP-1 is activated by cellular oxidative stress,
      and we have reported significant production of ROS by high glucose-cultured
      cells. We examined signaling pathways upstream of AP-1 in EC that lead to AP-1
      activation by HG. EC cultured in 25 mm glucose had a 2-fold increase in p38
      phosphorylation compared with control normal glucose-cultured EC. Inhibition of
      the p38 pathway using 5 microm SB203580 significantly reduced glucose-mediated IL
      8 mRNA production by 60%. Furthermore, blocking p38 pathway activation using a
      dominant-negative p38 construct significantly reduced glucose-mediated monocyte
      adhesion by 50%. Thus, glucose-stimulated monocyte adhesion is primarily
      regulated through phosphorylation of p38 with subsequent activation of AP-1,
      leading to IL-8 production. To study this pathway in the setting of diabetes, we
      used the db/db mouse. P38 phosphorylation was increased in diabetic db/db mice
      compared with control mice. We found a dramatic elevation in plasma levels of KC,
      the mouse ortholog of IL-8 in diabetic db/db mice (1800 +/- 100 pg/ml KC in db/db
      versus 300 +/- 75 pg/ml in C57BL/6J control mice, p < 0.0001). Inhibition of the
      p38 pathway in diabetic db/db mice significantly reduced monocyte adhesion by
      50%. Taken together, these data indicate that chronic elevated glucose in
      diabetes activates the p38 MAP kinase pathway to increase inflammatory IL-8 gene
      induction and monocyte/endothelial adhesion.

PMID- 15145957
TI  - Integrin-mediated cell adhesion to type I collagen fibrils.
AB  - In the integrin family, the collagen receptors form a structurally and
      functionally distinct subgroup. Two members of this subgroup, alpha(1)beta(1) and
      alpha(2)beta(1) integrins, are known to bind to monomeric form of type I
      collagen. However, in tissues type I collagen monomers are organized into large
      fibrils immediately after they are released from cells. Here, we studied collagen
      fibril recognition by integrins. By an immunoelectron microscopy method we showed
      that integrin alpha(2)I domain is able to bind to classical D-banded type I
      collagen fibrils. However, according to the solid phase binding assay, the
      collagen fibril formation appeared to reduce integrin alpha(1)I and alpha(2)I
      domain avidity to collagen and to lower the number of putative alphaI domain
      binding sites on it. Respectively, cellular alpha(1)beta(1) integrin was able to
      mediate cell spreading significantly better on monomeric than on fibrillar type I
      collagen matrix, whereas alpha(2)beta(1) integrin appeared still to facilitate
      both cell spreading on fibrillar type I collagen matrix and also the contraction
      of fibrillar type I collagen gel. Additionally, alpha(2)beta(1) integrin promoted
      the integrin-mediated formation of long cellular projections typically induced by
      fibrillar collagen. Thus, these findings suggest that alpha(2)beta(1) integrin is
      a functional cellular receptor for type I collagen fibrils, whereas
      alpha(1)beta(1) integrin may only effectively bind type I collagen monomers.
      Furthermore, when the effect of soluble alphaI domains on type I collagen fibril
      formation was tested in vitro, the observations suggest that integrin type
      collagen receptors might guide or even promote pericellular collagen
      fibrillogenesis.

PMID- 15145958
TI  - Chemical clamping allows for efficient phosphorylation of the RNA carrier protein
      Npl3.
AB  - Protein kinases phosphorylate the appropriate protein substrate by recognizing
      residues both proximal and distal to the site of phosphorylation. Although these
      distal contacts may provide excellent binding affinities (low Km values) through
      stabilization of the enzyme-substrate complex, these contacts could reduce
      catalytic turnover (decrease kcat) through slow phosphoprotein release. To
      investigate how protein kinases can overcome this problem and maintain both high
      substrate affinities and high turnover rates, the phosphorylation of the yeast
      RNA transport protein Npl3 by its natural protein kinase, Sky1p, was evaluated.
      Sky1p bound and phosphorylated Npl3 with a Km that was 2 orders of magnitude
      lower than a short peptide mimic representing the phosphorylation site and only
      proximal determinants. Surprisingly, this extraordinary difference is not the
      result of high affinity Npl3 binding. Rather, Npl3 achieves a low Km through a
      rapid and favorable phosphoryl transfer step. This step serves as a chemical
      clamp that locks the protein substrate in the active site without unduly
      stabilizing the product phosphoprotein and slowing its release. The chemical
      clamping mechanism offers an efficient means whereby a protein kinase can
      simultaneously achieve both high turnover and good substrate binding properties.

PMID- 15145959
TI  - Kinetics and binding sites for interaction of the prefoldin with a group II
      chaperonin: contiguous non-native substrate and chaperonin binding sites in the
      archaeal prefoldin.
AB  - Prefoldin is a jellyfish-shaped hexameric co-chaperone of the group II
      chaperonins. It captures a protein folding intermediate and transfers it to a
      group II chaperonin for completion of folding. The manner in which prefoldin
      interacts with its substrates and cooperates with the chaperonin is poorly
      understood. In this study, we have examined the interaction between a prefoldin
      and a chaperonin from hyperthermophilic archaea by immunoprecipitation, single
      molecule observation, and surface plasmon resonance. We demonstrate that
      Pyrococcus prefoldin interacts most tightly with its cognate chaperonin, and vice
      versa, suggesting species specificity in the interaction. Using truncation
      mutants, we uncovered by kinetic analyses that this interaction is multivalent in
      nature, consistent with multiple binding sites between the two chaperones. We
      present evidence that both N- and C-terminal regions of the prefoldin beta sub
      unit are important for molecular chaperone activity and for the interaction with
      a chaperonin. Our data are consistent with substrate and chaperonin binding sites
      on prefoldin that are different but in close proximity, which suggests a possible
      handover mechanism of prefoldin substrates to the chaperonin.

PMID- 15145960
TI  - ATP potentiates agrin-induced AChR aggregation in cultured myotubes: activation
      of RhoA in P2Y1 nucleotide receptor signaling at vertebrate neuromuscular
      junctions.
AB  - At vertebrate neuromuscular junctions, ATP is known to stabilize acetylcholine in
      the synaptic vesicles and to be co-released with it. We have shown previously
      that a nucleotide receptor, P2Y(1) receptor, is localized at the nmjs, and we
      propose that this mediates a trophic role for synaptic ATP there. In cultured
      myotubes, the activation of P2Y(1) receptors modulated agrin-induced
      acetylcholine receptor (AChR) aggregation in a potentiation manner. This
      potentiation effect in agrin-induced AChR aggregation was reduced by antagonizing
      the P2Y(1) receptors. The guanosine triphosphatase RhoA was shown to be
      responsible for this P2Y(1)-potentiated effect. The localization of RhoA in rat
      and chicken skeletal muscles was restricted at the neuromuscular junctions.
      Application of P2Y(1) agonists in cultured myotubes induced RhoA activation,
      which showed an additive effect with agrin-induced RhoA activation. Over
      expression of dominant-negative mutant of RhoA in cultured myotubes diminished
      the agrin-induced AChR aggregation, as well as the potentiation effect of P2Y(1)
      specific agonist. Application of UTP in the cultures also triggered similar
      responses as did 2-methylthioadenosine 5'-diphosphate, suggesting the involvement
      of other subtypes of P2Y receptors. These results demonstrate that RhoA could
      serve as a downstream mediator of signaling mediated by P2Y(1) receptor and
      agrin, which therefore synergizes the effects of the two neuron-derived trophic
      factors in modulating the formation and/or maintenance of post-synaptic apparatus
      at the neuromuscular junctions.

PMID- 15145961
TI  - Slac2-a/melanophilin contains multiple PEST-like sequences that are highly
      sensitive to proteolysis.
AB  - The synaptotagmin-like protein homologue lacking C2 domains-a (Slac2
      a)/melanophilin was recently identified as the "missing link" between the small
      GTPase Rab27A and the actin-based motor protein myosin Va. Although formation of
      a tripartite protein complex by three molecules had been shown to be required for
      proper melanosome distribution in melanocytes (Kuroda, T. S., Ariga, H., and
      Fukuda, M. (2003) Mol. Cell. Biol. 23, 5245-5255), the regulatory mechanisms of
      the complex (i.e. assembly and disassembly of the complex) had never been
      elucidated. In this study, we discovered that Slac2-a and a closely related
      isoform, Slac2-c/MyRIP, contain multiple PEST-like sequences (potential signals
      for rapid protein degradation) in the myosin Va- and actin-binding domains at the
      C terminus. We found that the C-terminal domain of Slac2-a is highly sensitive to
      low concentrations of proteases, such as trypsin and calpain, in vitro, whereas
      the N-terminal Rab27A-binding domain is highly resistant to these proteases. We
      further found that endogenous calpains selectively cleave Slac2-a, but not Rab27A
      or myosin Va, in melanocytes. A mutant Slac2-a lacking one of the PEST-like
      sequences located at the interface between the myosin Va- and actin-binding
      domains (DeltaPEST; amino acids 399-405) is more stable than the wild-type
      protein, both in vitro and in melanocytes. Expression of the mutant Slac2-a
      DeltaPEST with an N-terminal green fluorescence protein tag often induced
      perinuclear aggregation of melanosomes ( approximately 40% of the transfected
      cells) compared with the wild-type Slac2-a. Our findings suggest that protein
      degradation of Slac2-a is an essential process for proper melanosome distribution
      in melanocytes.

PMID- 15145962
TI  - Drug-drug, drug-dietary supplement, and drug-citrus fruit and other food
      interactions: what have we learned?
AB  - Serious drug-drug interactions have contributed to recent U.S. market withdrawals
      and also recent nonapprovals of a few new molecular entities. Many of these
      interactions involved the inhibition or induction of metabolizing enzymes and
      efflux transporters, resulting in altered systemic exposure and adverse drug
      reactions or loss of efficacy. In addition to drug-drug interactions, drug
      dietary supplement and drug-citrus fruit interactions, among others, could also
      cause adverse drug reactions or loss of efficacy and are important issues to
      consider in the evaluation of new drug candidates. This commentary reviews (1).
      the current understanding of the mechanistic basis of these interactions, (2).
      issues to consider in the interpretation of study results, and (3). recent
      labeling examples to illustrate the translation of study results to information
      useful for patients and health care providers.

PMID- 15145963
TI  - Limited sampling strategy of S-warfarin concentrations, but not warfarin S/R
      ratios, accurately predicts S-warfarin AUC during baseline and inhibition in
      CYP2C9 extensive metabolizers.
AB  - S-warfarin area under the concentration-time curve (AUC(0- infinity )) and
      clearance are used as measures of cytochrome p450 (CYP) 2C9 activity. In
      addition, warfarin S/R ratios are used to assess CYP2C9 activity. The
      determination of S-warfarin AUC(0- infinity ) requires multiple blood samples.
      Limited sampling strategy (LSS) is a validated technique that estimates AUC(0-
      infinity ) using limited blood samples. The objective of this study was to
      evaluate LSS of S-warfarin concentrations and warfarin S/R ratios to predict S
      warfarin AUC(0- infinity ) during CYP2C9 baseline activity and inhibition with
      fluvastatin. Fifty-one healthy subjects, genotyped as CYP2C9 extensive
      metabolizers, were administered oral warfarin 10 mg. Blood samples were collected
      over 96 hours. S-warfarin AUC(0- infinity ) equations were derived from a
      training set of 20 subjects using multiple linear regression. Validation of the
      equations used data from the remaining 31 subjects. All derived equations were
      within acceptable limits for measures of bias and precision. Single-point and two
      point S-warfarin concentrations, but not warfarin S/R ratios, were predictive of
      S-warfarin AUC(0- infinity ) during CYP2C9 baseline activity and inhibition. No
      correlation was observed between CYP2C9(*)1/(*)1 and (*)1/(*)2 genotypes and
      either S-warfarin concentrations or warfarin S/R ratios. The equation using two
      point S-warfarin concentrations at 24 and 48 hours was the most accurate
      predictor of S-warfarin AUC(0- infinity ). LSS using S-warfarin concentrations is
      an efficient and accurate technique to evaluate S-warfarin AUC(0- infinity ) when
      using warfarin as a CYP2C9 probe drug.

PMID- 15145964
TI  - The influence of St John's Wort on CYP2C19 activity with respect to genotype.
AB  - Induction of cytochrome p450 isozymes is the major cause for clinical drug
      interactions of St. John's wort. The relationships of St. John's wort to
      cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19
      is lacking. Thus, the aim of the present study was to observe the effect of St.
      John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult
      men-6 extensive metabolizers of CYP2C19 (2C19(*)1/2C19(*)1) and 6 poor
      metabolizers (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two
      phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort
      tablet or placebo three times daily for 14 days, and then the activities of
      CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found
      that St. John's wort treatment significantly increased CYP2C19 activity in
      CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion
      raised by 151.5% +/- 91.9% (p = 0.0156), whereas no significant alteration was
      observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration
      did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In
      conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians
      should pay great attention when St. John's wort is added to or withdrawn from an
      existing drug regimen containing substrates for such enzymes.

PMID- 15145965
TI  - Omeprazole as a CYP2C19 marker in Chinese subjects: assessment of its gene-dose
      effect and intrasubject variability.
AB  - The objective of this study was to determine the reliability of omeprazole as a
      marker for CYP2C19 activity in Chinese subjects. In 27 healthy male Chinese
      subjects, the CYP2C19 phenotype was first determined with the standard
      mephenytoin hydroxylation index (HI) method. Subsequently, the subjects were
      randomized in a three-way crossover manner to receive an oral 40-mg dose from
      each of three omeprazole formulations (as part of a bioequivalence study).
      Multiple blood samples were obtained over 12 hours, and plasma concentrations of
      omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone were determined by a high
      performance liquid chromatography (HPLC) method. Individual CYP2C19 genotype was
      determined by the polymerase chain reaction/restriction fragment length
      polymorphism method. To assess the specificity for CYP2C19 activity, the
      hydroxylation metabolic ratio (MR) of omeprazole (AUC(omeprazole)/AUC(5
      hydroxyomeprazole)) was compared to mephenytoin HI and related to CYP2C19
      genotype status. The inter- and intrasubject variabilities of MR were also
      calculated, and their magnitudes were compared. The intersubject MR varied more
      than 20 fold. Among the subjects, there was a gene-dose effect, and the mean MR
      was 1.76, 3.45, and 33.08, respectively, in the homozygous extensive metabolizers
      (wt/wt, n = 9), heterozygous extensive metabolizers (wt/m1 or wt/m2, n = 10), and
      poor metabolizers (m1/m1 or m1/m2, n = 7). However, the coefficients of variation
      for intrasubject MR only ranged from 4.5% to 33.7% over the three periods with
      the three formulations. The phenotype based on MR was concordant with HI. In view
      of the clear gene-dose effect, concordance with mephenytoin HI, and low
      intrasubject variability, omeprazole MR following a 40-mg oral dose can be
      considered as a specific and sensitive marker for CYP2C19 activity in Chinese
      subjects.

PMID- 15145966
TI  - Population pharmacokinetic analysis of anidulafungin, an echinocandin antifungal.
AB  - The objective of this analysis was to describe the pharmacokinetic
      characteristics of anidulafungin in patients with serious fungal disease based on
      pharmacokinetic data collected during four recently completed or ongoing Phase
      II/III clinical studies. A total of 600 anidulafungin plasma samples from 225
      patients across the four studies were available for analysis. Patients received
      daily intravenous infusions of 50, 75, or 100 mg anidulafungin, preceded by a
      loading dose that was twice the daily dose. The analysis population consisted of
      129 patients with esophageal candidiasis, 87 with invasive candidiasis, 7 with
      invasive aspergillosis, and 2 with azole refractory mucosal candidiasis. A
      population analysis approach was used to develop a steady-state pharmacokinetic
      model for anidulafungin, assess the significance of possible covariates, and
      determine the amount of intersubject and random residual variability. A two
      compartment model with first-order elimination provided the best fit to the data.
      The clearance of anidulafungin was influenced by weight and gender, and subjects
      in the invasive candidiasis study had a typical clearance that was approximately
      30% higher than subjects from other studies. Weight was determined to be a
      predictor of the central volume of distribution. The covariates on clearance
      accounted for less than 20% of the intersubject variability and therefore are
      deemed to be of little clinical relevance. There was no evidence that the
      presence of rifampin or metabolic substrates, inhibitors, or inducers of
      cytochrome p450 influenced the clearance of anidulafungin. This indicates that
      dosing adjustments are not necessary when anidulafungin is administered in the
      presence of medications falling into these classifications.

PMID- 15145967
TI  - Absorption of rivastigmine from different regions of the gastrointestinal tract
      in humans.
AB  - The objective of this study was to evaluate the rate and extent of absorption and
      metabolism of rivastigmine (Exelon), ENA 713) after site-specific delivery of the
      drug in the gastrointestinal (GI) tract using a naso-intestinal intubation
      technique. Healthy adult subjects (n = 7) received, on four separate occasions, a
      3-mg dose of a rivastigmine solution (2 mg/mL) orally and via a naso-intestinal
      tube to three GI sites (jejunum, ileum, and ascending colon). On each of the 3
      treatment days for regional GI dosing, the tube was progressed to each of the
      three GI sites, which was determined by a radiographical technique prior to
      dosing. On the fourth day, following tube withdrawal, the subject received a 3-mg
      oral dose of a rivastigmine solution. Plasma samples were obtained at different
      multiple time points, and the plasma concentrations of rivastigmine and its
      metabolite, NAP 226-90, were determined using a gas chromatography/mass
      spectrometry (GC/MS) method. Rivastigmine was rapidly absorbed following both
      oral administration and site-specific delivery to different regions of the GI
      tract (jejunum, ileum, and ascending colon). Compared with oral administration
      (AUV(0- infinity ) = 21 ng*h/mL, C(max) = 12.8 ng/mL, and t(max) = 0.87 h),
      delivery of the drug directly into the ileum, jejunum, and ascending colon did
      not change the extent of absorption, but the time to peak concentration appeared
      to be smaller (mean t(max) ranged from 0.4-0.6 h, with no change in C(max)). The
      relative bioavailability of rivastigmine from all three regions of the GI tract
      was comparable to that following oral administration. The metabolite levels (AUC,
      C(max)) were also similar among the three different regions of the GI tract when
      compared to the oral dose. It was concluded that rivastigmine is rapidly and
      equally well absorbed following an oral dose and after specific delivery to
      different regions of the small intestine and ascending colon. GI metabolism of
      rivastigmine to its major metabolite, NAP 226-90, occurs to a similar extent in
      different segments of the GI tract.

PMID- 15145968
TI  - Kinetics and EEG effects of midazolam during and after 1-minute, 1-hour, and 3
      hour intravenous infusions.
AB  - The objective of this study was to evaluate the kinetics and dynamics of
      midazolam when administered by three different infusion schemes, using
      electroencephalography to measure pharmacodynamic effects. In a three-way
      crossover study, 8 volunteers received midazolam (0.1 mg/kg) by constant-rate
      intravenous infusion. The durations of midazolam infusions for the three trials
      were 1 minute, 1 hour, and 3 hours. Plasma midazolam concentrations and
      electroencephalographic (EEG) activity in the 13- to 30-Hz range were monitored
      for 24 hours. Based on separate analysis of each subject-trial, mean values for
      volume of distribution and distribution or elimination half-life did not
      significantly vary. Central compartment volume and clearance differed among the
      three midazolam infusion trials; however, the magnitude of change was small. EEG
      activity in the 13- to 30-Hz range significantly increased for all three
      midazolam infusion trials. Plots of midazolam plasma concentration versus
      pharmacodynamic EEG effect for the 1-hour and 3-hour infusion trials did not
      reveal evidence of either counterclockwise or clockwise hysteresis. Plots from
      the 1-minute infusion trial demonstrated counterclockwise hysteresis, consistent
      with an equilibration effect-site delay. This was incorporated into a kinetic
      dynamic model in which hypothetical effect-site concentration was related to
      pharmacodynamic EEG effect via the sigmoid E(max) model. Analysis of all three
      infusion trials together yielded the following mean estimates: maximum EEG
      effect, 16.3% over baseline; 50% maximum effective concentration, 31 ng/mL; and
      an apparent rate constant for drug disappearance from the effect compartment
      which approached infinity. Despite the delay in effect onset during the 1-minute
      midazolam infusion, midazolam infusions in duration of up to 3 hours produce CNS
      sedation without evidence of tolerance.

PMID- 15145969
TI  - Single-dose pharmacokinetics of daptomycin in young and geriatric volunteers.
AB  - Daptomycin is a novel lipoprotein antibiotic that was recently approved for the
      treatment of complicated skin and skin structure infections caused by aerobic
      gram-positive bacteria. The pharmacokinetics of daptomycin was evaluated after a
      single 0.5-hour intravenous infusion of 4 mg/kg to groups of young adult (18-30
      years) and geriatric (>or= 75 years) volunteers. Daptomycin was safe and well
      tolerated. No adverse events related to the infusion were reported. With
      increased age, there were increases in the area under the plasma concentration
      time curve extrapolated to infinity (AUC( infinity )) and the terminal
      elimination half-life. Systemic (CL) and renal clearance (CL(R)) both decreased
      with increasing age. The observed changes seen in CL between the two cohorts were
      most likely a result of changes in renal function, as estimated by creatinine
      clearance. No statistically significant differences were observed between the two
      groups in the maximum plasma concentration (C(max)) and volume of distribution at
      steady state (Vd(ss)). The confidence intervals for the arithmetic mean ratios of
      the fraction of the dose excreted in the urine as daptomycin (%Fe) (geriatric
      subjects over younger subjects) were 60% to 101%, indicating that %Fe(dose) was
      lower in geriatric subjects. These results demonstrate that changes in the
      pharmacokinetics of daptomycin in the elderly are attributable to changes in
      renal function, whereas age per se is not a significant factor.

PMID- 15145970
TI  - Optimizing dose selection with modeling and simulation: application to the
      vasopeptidase inhibitor M100240.
AB  - Dual inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin-converting
      enzyme (ACE) has gained increasing interest in the treatment of hypertension,
      heart failure, and renoprotection. Specifically, M100240, the thioester of the
      dual ACE/NEP inhibitor MDL100,173, has been evaluated in the management of
      hypertension. A model-based analysis, including simulations, was employed to
      characterize the relationship between individual M100240 drug exposure and
      neurohormonal response and to optimize the dose selection for future clinical
      studies. Sixty-two healthy subjects and 189 hypertensive patients were studied
      after oral once-daily administration of 2.5, 5, 10, 25, or 50 mg M100240.
      Pharmacokinetic-biomarker and blood pressure response models were fitted to the
      data with the computer program NONMEM. A direct inhibitory E(max) model
      adequately described the relationship between MDL100,173 concentration and ACE
      activity. No clear concentration or dose-dependent NEP or blood pressure
      responses were evident. Given a target 90% ACE inhibition, simulation reveals
      that (1). 50 mg M100240 once daily produces adequate ACE inhibition 24 hours
      postdose in only 20% of subjects, and (2). higher and/or more frequent doses on
      the order of 25 mg three times daily or 50 mg twice daily are required to achieve
      the target ACE inhibition in at least 50% of patients over 24 hours. Insufficient
      blood pressure-lowering effects were observed in healthy subjects and
      hypertensive patients due to inadequate ACE and NEP inhibition with once-daily
      oral doses of up to 50 mg of M100240. Divided doses might provide target ACE
      inhibition in more patients.

PMID- 15145971
TI  - Benefits of individualized counseling by the pharmacist on the treatment outcomes
      of hyperlipidemia in Hong Kong.
AB  - A prospective controlled study on the benefits of pharmacists' individualized
      counseling on drug compliance, cholesterol concentration reduction, attainment of
      National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)
      low-density lipoprotein cholesterol (LDL-C) goals, and patient satisfaction was
      carried out in a private community hospital in Hong Kong. All patients who were
      newly prescribed with lipid-lowering drugs for primary prevention were included.
      The patients in the individualized counseling group received "intense" counseling
      and follow-up of cholesterol concentration by a pharmacist for 3 months. The
      control group received routine counseling. Fifty patients completed the study (26
      in the individualized group, 24 in the control group). Compliance was assessed,
      and those patients who achieved 75% compliance were defined as compliers. In the
      individualized group, 76.9% were compliers compared with 41.7% in the control
      group (p < 0.01). The individualized group achieved 28.3%, 27.7%, and 26.1%
      reduction in total cholesterol, LDL-C, and triglycerides, respectively, compared
      with 15.3%, 16.3%, and 10.6% in the control group (p < 0.05 for all). Also in the
      individualized group, 80.8% achieved the ATP III LDL-C goals compared to 58.3% in
      the control group (p < 0.05). Of patients in the individualized group, 85% felt
      that the pharmacist counseling service could improve their disease management.
      The study demonstrated that pharmacists' individualized counseling, together with
      the assessment of cholesterol concentrations, had positive impacts on the
      management of hyperlipidemia, including improved drug compliance, better
      treatment endpoints, and patient satisfaction.

PMID- 15145972
TI  - Influence of omeprazole on bioavailability of bismuth following administration of
      a triple capsule of bismuth biskalcitrate, metronidazole, and tetracycline.
AB  - The objective of this study was to determine the impact of omeprazole on bismuth
      (Bi) bioavailability when given in a three-in-one capsule containing bismuth
      biskalcitrate, metronidazole, and tetracycline. Thirty-four healthy volunteers
      were randomly assigned to receive three capsules (each containing bismuth
      biskalcitrate 140 mg + metronidazole 125 mg + tetracycline 125 mg) qid alone x 6
      days or the same treatment + omeprazole (OM) 20 mg bid. Blood was drawn at
      intervals for 24 hours after the last dose. After the last dose, mean (CV) C(min)
      for plasma bismuth was 2882 pg/mL (36%) and 1195 pg/mL (23%) (p< 0.001), with and
      without OM, respectively. Mean (CV) C(max) was 25493 pg/mL (69%) and 8061 pg/mL
      (28%) (p < 0.001) with and without OM, respectively. AUC(0-24) increased by 2.9
      in presence of OM (p < 0.001). Adverse events in both groups were usually mild
      and of a gastrointestinal nature, and all had resolved by the end of the trial.
      This study confirms an interaction between Bi biskalcitrate and OM. Risk of Bi
      toxicity, seen after long-term use of Bi compounds, is minimal here because
      plasma levels of Bi remained well below the toxic levels of 50 microg/L, and the
      treatment period with this triple capsule + OM is only 10 days, a substantially
      lower number of days compared to that which might produce Bi toxicity.

PMID- 15145973
TI  - Concomitant administration of lumiracoxib and a triphasic oral contraceptive does
      not affect contraceptive activity or pharmacokinetic profile.
AB  - This study evaluated the effect of lumiracoxib on the pharmacokinetics and
      pharmacodynamics of ethinyl estradiol (EE) and levonorgestrel (LN) in Triphasil
      28 (a triphasic oral contraceptive). Females stabilized on Triphasil-28 continued
      on Triphasil-28 alone for another month (Treatment Period 1), then also received
      lumiracoxib (400 mg daily) or placebo for 28 days each (Periods 2 and 3) in a
      double-blind crossover design. Plasma pharmacokinetic profiles were assessed on
      Day 21 of Periods 2 and 3. Progesterone and plasma sex hormone binding globulin
      (SHBG) concentrations were measured before and 2 hours after Triphasil-28
      administration on Day 21 of all three treatment periods. Lumiracoxib had no
      significant effect on EE or LN pharmacokinetics or on progesterone or SHBG
      concentrations, indicating that anovulation and Triphasil-28 effectiveness was
      maintained. Adverse events were similar for lumiracoxib and placebo. Therefore,
      no clinically important consequences are anticipated if lumiracoxib is
      coadministered with oral contraceptives containing EE or LN.

PMID- 15145975
TI  - Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of
      NIH3T3 cells: involvement of a cannabinoid 1-like receptor.
AB  - Mouse fibroblast cells overexpressing phosphatidylinositol transfer protein alpha
      [PI-TPalpha; sense PI-TPalpha (SPIalpha) cells] show a significantly increased
      rate of proliferation and an extreme resistance toward ultraviolet- or tumor
      necrosis factor-alpha-induced apoptosis. The conditioned medium (CM) from
      SPIalpha cells or the neutral lipid extract from CM stimulated the proliferation
      of quiescent wild-type NIH3T3 cells. CM was also highly effective in increasing
      resistance toward induced apoptosis in both wild-type cells and the highly
      apoptosis-sensitive SPIbeta cells (i.e., wild-type cells overexpressing PI
      TPbeta). CM from SPIalpha cells grown in the presence of NS398, a specific
      cyclooxygenase-2 (COX-2) inhibitor, expressed a diminished mitogenic and
      antiapoptotic activity. This strongly suggests that at least one of the bioactive
      factor(s) is an eicosanoid. In accordance, SPIalpha cells express enhanced levels
      of COX-1 and COX-2. The antiapoptotic activity of CM from SPIalpha cells tested
      on SPIbeta cells was inhibited by approximately 50% by pertussis toxin and
      suramin as well as by SR141716A, a specific antagonist of the cannabinoid 1
      receptor. These inhibitors had virtually no effect on the COX-2-independent
      antiapoptotic activity of CM from SPIalpha cells. The latter results imply that
      PI-TPalpha mediates the production of a COX-2-dependent eicosanoid that activates
      a G-protein-coupled receptor, most probably a cannabinoid 1-like receptor.

PMID- 15145976
TI  - The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment:
      evidence for multiple redundant pathways.
AB  - A portion of apolipoprotein E (apoE) internalized by hepatocytes is spared
      degradation and is recycled. To investigate the intracellular routing of
      recycling apoE, primary hepatocyte cultures from LDL receptor-deficient mice and
      mice deficient in receptor-associated protein [a model of depressed expression of
      LDL receptor-related protein (LRP)] were incubated with human VLDL containing
      125I-labeled human recombinant apoE3. Approximately 30% of the internalized
      intact apoE was recycled after 4 h. The N-terminal 22 kDa fragment of apoE was
      also resecreted, demonstrating that this apoE domain contains sufficient sequence
      to recycle. The 22 kDa fragment has reduced affinity for lipoproteins, suggesting
      that apoE recycling is linked to the ability of apoE to bind directly to a
      recycling receptor. Finally, apoE was found to recycle equally well in the
      presence of brefeldin A, a drug that blocks transport from the endoplasmic
      reticulum and leads to collapse of the Golgi stacks. Our studies demonstrate that
      apoE recycling occurs 1) in the absence of the LDL receptor or under conditions
      of markedly reduced LRP expression; 2) when apoE lacks the carboxyl-terminal
      domain, which allows binding to the lipoprotein; and 3) in the absence of an
      intact Golgi apparatus. We conclude that apoE recycling occurs through multiple
      redundant pathways.

PMID- 15145977
TI  - Identification of intermediates in the bile acid synthetic pathway as ligands for
      the farnesoid X receptor.
AB  - Bile acid synthesis from cholesterol is tightly regulated via a feedback
      mechanism mediated by the farnesoid X receptor (FXR), a nuclear receptor
      activated by bile acids. Synthesis via the classic pathway is initiated by a
      series of cholesterol ring modifications and followed by the side chain cleavage.
      Several intermediates accumulate or are excreted as end products of the pathway
      in diseases involving defective bile acid biosynthesis. In this study, we
      investigated the ability of these intermediates to activate human FXR. In a cell
      based reporter assay and coactivator recruitment assays in vitro, early
      intermediates possessing an intact cholesterol side chain were inactive, whereas
      26- or 25-hydroxylated bile alcohols and C27 bile acids were highly efficacious
      ligands for FXR at a level comparable to that of the most potent physiological
      ligand, chenodeoxycholic acid. Treatment of HepG2 cells with these precursors
      repressed the rate-limiting cholesterol 7alpha-hydroxylase mRNA level and induced
      the small heterodimer partner and the bile salt export pump mRNA, indicating the
      ability to regulate bile acid synthesis and excretion. Because 26-hydroxylated
      bile alcohols and C27 bile acids are known to be evolutionary precursors of bile
      acids in mammals, our findings suggest that human FXR may have retained affinity
      to these precursors during evolution.

PMID- 15145978
TI  - Phorbol ester promotes histone H3-Ser10 phosphorylation at the LDL receptor
      promoter in a protein kinase C-dependent manner.
AB  - Histone modification is emerging as a major regulatory mechanism for modulating
      gene expression by altering the accessibility of transcription factors to DNA.
      This study unravels the relationship between histone H3 modifications and LDL
      receptor induction, focusing also on routes by which phosphorylation is mediated
      in human hepatoma HepG2 cells. We show that while histone H3 is constitutively
      acetylated at LDL receptor chromatin, 12-O-tetradecanoylphorbol-13-acetate (TPA)
      causes rapid hyperphosphorylation of histone H3 on serine 10 (histone H3-Ser10),
      despite global reduction in its phosphorylation levels. Ser10
      hyperphosphorylation precedes LDL receptor induction and is independent of the
      p42/44MAPK, p38MAPK, pp90RSK, or MSK-1 cascade. Interestingly, inhibition of
      protein kinase C (PKC) blocks Ser10 hyperphosphorylation and also compromises LDL
      receptor induction by TPA. Consistent with its role, recombinant purified PKC
      phosphorylate purified histone H3-Ser10. Collectively, our findings highlight a
      novel role for PKC in regulating histone H3-Ser10 phosphorylation and suggest
      that histone modification provides numerous regulatory opportunities to set the
      overall range of control attainable for LDL receptor gene induction.

PMID- 15145979
TI  - High dietary intake of phytosterol esters decreases carotenoids and increases
      plasma plant sterol levels with no additional cholesterol lowering.
AB  - The objective of this study was to measure the effects on serum lipids and plasma
      phytosterols of 6.6 g/day phytosterols from three foods (bread, breakfast cereal,
      and spread) consumed for 12 weeks compared with a diet that was not enriched with
      phytosterols. Thirty-five subjects undertook a nonrandomized, single-blind study
      consisting of a 2 week baseline period, 6 weeks on high-phytosterol intake, 6
      weeks on high-phytosterol intake plus increased fruit and vegetable intake, and a
      final 2 week washout period. Serum total cholesterol decreased by 8.3% from 6.59
      to 6.04 mmol/l, and LDL cholesterol decreased by 12.6% from 4.44 to 3.88 mmol/l.
      Plasma phytosterol levels increased by 45% (sitosterol) and 105% (campesterol).
      Cholesterol-adjusted plasma alpha- and beta-carotene levels decreased by 19-23%,
      lutein by 14%, and lycopene by 11%. Levels of alpha-carotene and lutein increased
      with extra fruit and vegetables. Only lycopene failed to increase during the
      washout phase. There were no significant changes in biochemical parameters. Serum
      LDL cholesterol lowering with 6.6 g/day ingested phytosterols was in the range
      seen with 1.6-3.2 g/day phytosterols. Lowering of plasma carotenoids was greater
      than that seen with lower phytosterol intake and was partially reversed by
      increased fruit and vegetable intake.

PMID- 15145981
TI  - The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL
      mediated triglyceride hydrolysis.
AB  - The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride
      (TG)-derived FFA by facilitating the expression of lipoprotein lipase (LPL).
      However, vldlr-/- mice do not show altered plasma lipoprotein levels, despite
      reduced LPL expression. Because LPL activity is crucial in postprandial lipid
      metabolism, we investigated whether the VLDLr plays a role in chylomicron
      clearance. Fed plasma TG levels of vldlr-/- mice were 2.5-fold increased compared
      with those of vldlr+/+ littermates (1.20 +/- 0.37 mM vs. 0.47 +/- 0.18 mM; P <
      0.001). Strikingly, an intragastric fat load led to a 9-fold increased
      postprandial TG response in vldlr-/- compared with vldlr+/+ mice (226 +/- 188
      mM/h vs. 25 +/- 11 mM/h; P < 0.05). Accordingly, the plasma clearance of [3H]TG
      labeled protein-free chylomicron-mimicking emulsion particles was delayed in
      vldlr-/- compared with vldlr+/+ mice (half-life of 12.0 +/- 2.6 min vs. 5.5 +/-
      0.9 min; P < 0.05), with a 60% decreased uptake of label into adipose tissue (P <
      0.05). VLDLr deficiency did not affect the plasma half-life and adipose tissue
      uptake of albumin-complexed [14C]FFA, indicating that the VLDLr facilitates
      postprandial LPL-mediated TG hydrolysis rather than mediating FFA uptake. We
      conclude that the VLDLr plays a major role in the metabolism of postprandial
      lipoproteins by enhancing LPL-mediated TG hydrolysis.

PMID- 15145980
TI  - Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in
      Th1-polarized murine CD4+ T-cells.
AB  - Dietary n-3 PUFAs have been shown to attenuate T-cell-mediated inflammation. To
      investigate whether dietary n-3 PUFAs promote activation-induced cell death
      (AICD) in CD4+ T-cells induced in vitro to a polarized T-helper1 (Th1) phenotype,
      C57BL/6 mice were fed diets containing either 5% corn oil (CO; n-6 PUFA control)
      or 4% fish oil (FO) plus 1% CO (n-3 PUFA) for 2 weeks. Splenic CD4+ T-cells were
      cultured with alpha-interleukin-4 (alphaIL-4), IL-12, and IL-2 for 2 days and
      then with recombinant (r) IL-12 and rIL-2 for 3 days in the presence of diet
      matched homologous mouse serum (HMS) to prevent loss of cell membrane fatty
      acids, or with fetal bovine serum. After polarization, Th1 cells were reactivated
      and analyzed for interferon-gamma and IL-4 by intracellular cytokine staining and
      for apoptosis by Annexin V/propidium iodide. Dietary FO enhanced Th1 polarization
      by 49% (P = 0.0001) and AICD by 24% (P = 0.0001) only in cells cultured in the
      presence of HMS. FO enhancement of Th1 polarization and AICD after culture was
      associated with the maintenance of eicosapentaenoic acid (20:5n-3) and
      docosahexaenoic acid (22:6n-3) in plasma membrane lipid rafts. In conclusion, n-3
      PUFAs enhance the polarization and deletion of proinflammatory Th1 cells,
      possibly as a result of alterations in membrane microdomain fatty acid
      composition.

PMID- 15145982
TI  - Subcellular localization of the mosquito sterol carrier protein-2 and sterol
      carrier protein-x.
AB  - Subcellular distribution of Aedes aegypti sterol carrier protein-2 (AeSCP-2) and
      AeSCP-x was studied using electron microscopy. In both cultured A. aegypti cells
      and in the larval midgut, AeSCP-2 was detected mostly in the cytosol, with some
      labeling mitochondria and nucleus, but not in membranous vesicles. The widespread
      distribution of AeSCP-2 in the midgut epithelium is consistent with its potential
      lipid transfer function in all phases of cholesterol absorption. In contrast,
      AeSCP-x was found mostly in the peroxisome. Differences in the subcellular
      distribution of AeSCP-2 and AeSCP-x suggest that these two members of the SCP-2
      gene family are functionally distinct. Overexpression of AeSCP-2 in A. aegypti
      cells showed increased localization of AeSCP-2 to cytosol, mitochondria, and
      nucleus. This is the first report on the nuclear distribution of an SCP.
      Overexpression of AeSCP-2 resulted in increased cholesterol incorporation in
      cells, suggesting that AeSCP-2 enhances cholesterol uptake.

PMID- 15145983
TI  - Lipoprotein cholesteryl ester production, transfer, and output in vivo in humans.
AB  - Our aim was to identify and quantify the major in vivo pathways of lipoprotein
      cholesteryl ester transport in humans. Normal (n = 7), bile fistula (n = 5), and
      familial hypercholesterolemia (FH; n = 1) subjects were studied. Each received
      isotopic free cholesterol in HDL, LDL, or particulate form, along with another
      isotope of free or esterified cholesterol or mevalonic acid. VLDL, intermediate
      density lipoprotein (IDL), LDL, HDL, blood cells, and bile were collected for up
      to 6 days for analysis of radioactivity and mass of free and esterified
      cholesterol. These raw data were subjected to compartmental analysis using the
      SAAM program. Results in all groups corroborated net transport of free
      cholesterol to the liver from HDL, shown previously in fistula subjects. New
      findings revealed that 70% of ester was produced from free cholesterol in HDL and
      30% from free cholesterol in LDL, IDL, and VLDL. No evidence was found for tissue
      produced ester in plasma. There was net transfer of cholesteryl ester to VLDL and
      IDL from HDL and considerable exchange between LDL and HDL. Irreversible ester
      output was from VLDL, IDL, and LDL, but very little was from HDL, suggesting that
      selective and holoparticle uptakes of HDL ester are minor pathways in humans. It
      follows that 1) they contribute little to reverse transport, 2) very high HDL
      would not result from defects thereof, and 3) the clinical benefit of high HDL is
      likely explained by other mechanisms. Reverse transport in the subjects with bile
      fistula and FH was facilitated by ester output to the liver from VLDL plus IDL.

PMID- 15145984
TI  - Hepatic secretion of small lipoprotein particles in apobec-1-/- mice is regulated
      by the LDL receptor.
AB  - Recent studies have examined the role of the LDL receptor (LDLR) in regulating
      murine hepatic lipoprotein production and apolipoprotein B (apoB) secretion, with
      divergent conclusions from in vivo versus in vitro approaches. We have re
      examined this question, both in vivo and in vitro, using apobec-1-/- mice to
      model the pattern of human hepatic apoB-100 secretion. Hepatic triglyceride
      production in vivo (using Triton WR-1339) was unchanged in wild-type (WT)
      C57BL/6, apobec-1-/-, ldlr-/-, and [apobec-1-/-, ldlr-/-] mice, while apoB-100
      production (using [35S]methionine incorporation) was increased > 2-fold in
      [apobec-1-/-, ldlr-/-] mice. Although > 90% of newly synthesized apoB floated
      within the d < 1.006 fraction of serum from all genotypes, fast-performance
      liquid chromatography separation revealed that nascent triglyceride-rich
      particles from [apobec-1-/-, ldlr-/-] mice, but not WT, apobec-1-/-, or ldlr-/-
      mice, distributed into smaller (intermediate and LDL-sized) particles. Studies in
      isolated hepatocytes from these different genotypes confirmed secretion of
      smaller particles exclusively from [apobec-1-/-, ldlr-/-] mice, and pulse-chase
      analysis demonstrated increased secretion of apoB-100 with virtual elimination of
      posttranslational degradation. These results directly support the suggestion that
      the LDLR regulates hepatic apoB-100 production and modulates secretion of small,
      triglyceride-rich particles, both in vivo and in vitro.

PMID- 15145985
TI  - Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides.
AB  - CYP4F isoforms are involved in the oxidation of important cellular mediators such
      as leukotriene B4 (LTB4) and prostaglandins. The proinflammatory agent LTB4 and
      cytotoxic leukotoxins have been associated with several inflammatory diseases. We
      present evidence that the hydroxylation of Z 9(10)-epoxyoctadecanoic, Z 9(10)
      epoxyoctadec-Z 12-enoic, and Z 12(13)-epoxyoctadec-Z 9-enoic acids and that of
      monoepoxides from arachidonic acid [epoxyeicosatrienoic acid (EET)] is important
      in the regulation of leukotoxin and EET activity. These three epoxidized
      derivatives from the C18 family (C18-epoxides) were converted to 18-hydroxy-C18
      epoxides by human hepatic microsomes with apparent Km values of between 27.6 and
      175 microM. Among recombinant P450 enzymes, CYP4F2 and CYP4F3B catalyzed mainly
      the omega-hydroxylation of C18-epoxides with an apparent Vmax of between 0.84 and
      15.0 min(-1), whereas the apparent Vmax displayed by CYP4F3A, the isoform found
      in leukocytes, ranged from 3.0 to 21.2 min(-1). The rate of omega-hydroxylation
      by CYP4A11 was experimentally found to be between 0.3 and 2.7 min(-1). CYP4F2 and
      CYP4F3 exhibited preferences for omega-hydroxylation of Z 8(9)-EET, whereas human
      liver microsomes preferred Z 11(12)-EET and, to a lesser extent, Z 8(9)-EET.
      Moreover, vicinal diol from both C18-epoxides and EETs were omega-hydroxylated by
      liver microsomes and by CYP4F2 and CYP4F3. These data support the hypothesis that
      the human CYP4F subfamily is involved in the omega-hydroxylation of fatty acid
      epoxides. These findings demonstrate that another pathway besides conversion to
      vicinal diol or chain shortening by beta-oxidation exists for fatty acid epoxide
      inactivation.

PMID- 15145986
TI  - Raising HDL cholesterol without inducing hepatic steatosis and
      hypertriglyceridemia by a selective LXR modulator.
AB  - Liver X receptors (LXRs) are ligand-activated transcription factors that belong
      to the nuclear receptor superfamily. LXRs activate transcription of a spectrum of
      genes that regulate reverse cholesterol transport, including the ATP binding
      cassette transporter A1 (ABCA1), and raise HDL cholesterol (HDL-C) levels.
      However, LXR agonists also induce genes that stimulate lipogenesis, including the
      sterol response element binding protein (SREBP1-c) and fatty acid synthetase
      (FAS). The induction of these genes in the liver cause increased hepatic
      triglyceride synthesis, hypertriglyceridemia, and hepatic steatosis. As LXR
      response elements have been identified in these promoters, it is not clear if
      these two processes can be separated. Herein, we demonstrate that plasma HDL-C
      elevation and intestinal ABCA1 induction can occur with relatively little
      induction of FAS and SREBP1-c in mouse liver via a selective LXR modulator
      GW3965. This is in contrast to the strong induction of hepatic lipogenic genes by
      the well-characterized LXR agonist T0901317 (T317). Consistent with the in vivo
      results, GW3965 is a very weak LXR activator compared with T317 in human hepatoma
      cells. GW3965-liganded LXR recruits selected coactivators less effectively than
      T317 and may explain in part the tissue selective gene induction. This
      demonstration that tissue and gene selective modulation is possible with
      selective LXR modulators has positive implications for the development of this
      class of antiatherosclerotic agents.

PMID- 15145987
TI  - Storage of human plasma samples leads to alterations in the lipoprotein
      distribution of apoC-III and apoE.
AB  - The effect of frozen storage on lipoprotein distribution of apolipoprotein C-III
      (apoC-III) and apoE was investigated by measuring apoC-III and apoE by ELISA in
      HDL and apoB-containing lipoproteins of human plasma samples (n = 16) before and
      after 2 weeks of frozen storage (-20 degrees C). HDLs were separated by heparin
      manganese precipitation (HMP) or by fast-protein liquid chromatography (FPLC).
      Total plasma apoC-III and apoE levels were not affected by frozen storage. HDL
      HMP apoC-III and apoE levels were significantly higher in frozen versus fresh
      samples: 7.7 +/- 0.7 versus 6.7 +/- 0.7 mg/dl (P < 0.05) and 2.0 +/- 0.1 versus
      1.2 +/- 0.1 mg/dl (P < 0.001), respectively. HDL-FPLC apoC-III and apoE, but not
      triglyceride (TG) or cholesterol, levels were also higher in frozen samples: 12.0
      +/- 1.2 versus 7.5 +/- 0.6 mg/dl (P < 0.001) and 2.7 +/- 0.2 versus 1.6 +/- 0.2
      mg/dl (P < 0.001), respectively. Frozen storage led to a decrease in apoC-III (
      17 +/- 9%) and apoE (-19 +/- 9%) in triglyceride-rich lipoprotein. Redistribution
      of apoC-III and apoE was most evident in samples with high TG levels. HDL apoC
      III and apoE levels were also significantly higher when measured in plasma stored
      at -80 degrees C. Our results demonstrate that lipoprotein distribution of apoC
      III and apoE is affected by storage of human plasma, suggesting that analysis of
      frozen plasma should be avoided in studies relating lipoprotein levels of apoC
      III and/or apoE to the incidence of coronary artery disease.

PMID- 15145989
TI  - The International classification of headache disorders, 2nd edn (ICDH-II).
AB  - Better classification of headache disorders enables better headache research,
      understanding of headache, communication, and, ultimately, management of a set of
      disabling neurological disorders.

PMID- 15145988
TI  - Aneurysm surgery after the International Subarachnoid Aneurysm Trial (ISAT).

PMID- 15145990
TI  - Clinical and radiological predictors of recanalisation: time to define a rapid
      scoring system.

PMID- 15145991
TI  - Monitoring and interpretation of intracranial pressure.
AB  - Intracranial pressure (ICP) is derived from cerebral blood and cerebrospinal
      fluid (CSF) circulatory dynamics and can be affected in the course of many
      diseases of the central nervous system. Monitoring of ICP requires an invasive
      transducer, although some attempts have been made to measure it non-invasively.
      Because of its dynamic nature, instant CSF pressure measurement using the height
      of a fluid column via lumbar puncture may be misleading. An averaging over 30
      minutes should be the minimum, with a period of overnight monitoring in conscious
      patients providing the optimal standard. Computer-aided recording with online
      waveform analysis of ICP is very helpful. Although there is no "Class I"
      evidence, ICP monitoring is useful, if not essential, in head injury, poor grade
      subarachnoid haemorrhage, stroke, intracerebral haematoma, meningitis, acute
      liver failure, hydrocephalus, benign intracranial hypertension, craniosynostosis
      etc. Information which can be derived from ICP and its waveforms includes
      cerebral perfusion pressure (CPP), regulation of cerebral blood flow and volume,
      CSF absorption capacity, brain compensatory reserve, and content of vasogenic
      events. Some of these parameters allow prediction of prognosis of survival
      following head injury and optimisation of "CPP-guided therapy". In hydrocephalus
      CSF dynamic tests aid diagnosis and subsequent monitoring of shunt function.

PMID- 15145992
TI  - White matter hyperintensities are significantly associated with cortical atrophy
      in Alzheimer's disease.
AB  - BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white
      matter hyperintensities (WMH) in dementia may explain inconsistent reports of its
      prevalence and impact on cognition. We used a method of brain MRI segmentation
      for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and
      examined the association between WMH and structural and cognitive variables.
      METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for
      probable AD was studied. Nineteen healthy volunteers of comparable age served as
      the control group. Patients had a complete neurological and neuropsychological
      evaluation, and a three dimensional MRI was obtained. Images were segmented into
      grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented
      images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild
      and moderate to severe AD patients had significantly more WMH than controls
      (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely
      correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were
      significantly associated with vascular risk factors and with a worse performance
      on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD
      demonstrated that WMH are significantly related to cortical atrophy and
      neuropsychological impairment.

PMID- 15145993
TI  - Risk and protective effects of the APOE gene towards Alzheimer's disease in the
      Kungsholmen project: variation by age and sex.
AB  - BACKGROUND: The risk effect of APOE epsilon 4 allele for Alzheimer's disease is
      acknowledged, whereas the putative protective effect of epsilon 2 allele remains
      in debate. OBJECTIVES: To investigate whether those inconsistent findings may be
      attributable to differences in age and sex composition of the study populations.
      METHODS: A community dementia free cohort (n = 985) aged > or =75 years was
      followed up to detect Alzheimer's disease cases (DSM-III-R criteria). Data were
      analysed using Cox models with adjustment for major potential confounders.
      RESULTS: Over a median 5.6 year follow up, Alzheimer's disease was diagnosed in
      206 subjects. Compared with APOE epsilon 3/epsilon 3 genotype, the relative risk
      (RR) of Alzheimer's disease was 1.4 (95% confidence interval (CI), 1.0 to 2.0; p
      = 0.03) for heterozygous epsilon 4 allele and 3.1 (95% CI, 1.6 to 5.9) for
      homozygous epsilon 4 allele. The association between epsilon 4 allele and
      Alzheimer's disease risk was stronger in men than in women (RR related to the
      interaction term epsilon 4 allele by sex, 0.4; 95% CI, 0.2 to 0.9). The epsilon 4
      allele accounted for one third of Alzheimer's disease cases among men, but only
      one tenth among women. The epsilon 2 allele was related to a reduced Alzheimer's
      disease risk mainly in people aged <85 years (RR, 0.4; 95% CI, 0.2 to 0.8). The
      RR of Alzheimer's disease related to the interaction term of epsilon 2 allele by
      age was 2.4 (95% CI, 1.0 to 6.0; p = 0.06). CONCLUSIONS: The APOE genotype
      specific effects on Alzheimer's disease vary by age and sex, in which the epsilon
      4 allele has a stronger risk effect in men, and the epsilon 2 allele confers a
      protective effect only in younger-old people.

PMID- 15145994
TI  - Neurosyphilis with complex partial status epilepticus and mesiotemporal MRI
      abnormalities mimicking herpes simplex encephalitis.

PMID- 15145995
TI  - Long term effects of bilateral subthalamic nucleus stimulation on cognitive
      function, mood, and behaviour in Parkinson's disease.
AB  - BACKGROUND: Long term effects of subthalamic nucleus (STN) stimulation on
      cognition, mood, and behaviour are unknown. OBJECTIVE: This study evaluated the
      cognitive, mood, and behavioural effects of bilateral subthalamic nucleus deep
      brain stimulation (STN DBS) in patients with Parkinson's disease (PD) followed up
      for three years. METHODS: A consecutive series of 77 PD patients was assessed
      before, one, and three years after surgery. Mean (SD) age at surgery was 55 (8).
      Seven patients died or were lost for follow up. Neuropsychological assessment
      included a global cognitive scale, memory, and frontal tests. Depression was
      evaluated using the Beck depression inventory. Assessment of thought disorders
      and apathy was based on the unified Parkinson's disease rating scale. Reports of
      the behavioural changes are mainly based on interviews done by the same
      neuropsychologist at each follow up. RESULTS: Only two cognitive variables
      worsened (category fluency, total score of fluency). Age was a predictor of
      decline in executive functions. Depression improved whereas apathy and thought
      disorders worsened. Major behavioural changes were two transient aggressive
      impulsive episodes, one suicide, four suicide attempts, one permanent apathy, one
      transient severe depression, four psychoses (one permanent), and five hypomania
      (one permanent). CONCLUSIONS: Comparing baseline, one year, and three year
      postoperative assessments, STN stimulation did not lead to global cognitive
      deterioration. Apathy scores mildly increased. Depression scores mildly improved.
      Behavioural changes were comparatively rare and mostly transient. Single case
      reports show the major synergistic effects of both medication and stimulation on
      mood and behaviour, illustrating the importance of a correct postoperative
      management.

PMID- 15145996
TI  - Altered cerebellar functional connectivity mediates potential adaptive plasticity
      in patients with multiple sclerosis.
AB  - BACKGROUND: The cerebellum is of potential interest for understanding adaptive
      responses in motor control in patients with multiple sclerosis because of the
      high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the
      relative roles of interactions between the neocortex and the cerebellum using
      measures of functional connectivity. METHODS: A role for altered neocortical
      cerebellar functional connectivity in adaptive responses to injury from multiple
      sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI)
      during figure writing with the dominant right hand in patients with predominantly
      early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a
      more bihemispheric pattern of activation in motor cortex than healthy controls (n
      = 11). Correlations between task related signal changes in neocortical and
      cerebellar regions of interest were used as a measure of functional connectivity.
      Healthy controls showed strong functional connectivity between the left motor
      cortex and the right cerebellar dentate nucleus. Significant connectivity between
      the left primary motor cortex and the right dentate was not found in patients.
      However, patients had significant connectivity between the left premotor
      neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not
      found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar
      neocortical functional connectivity may mediate potentially adaptive changes in
      brain motor control in patients with multiple sclerosis. Similar changes in the
      cerebellum and premotor cortex have been reported in the healthy brain during
      motor learning, suggesting that common mechanisms may contribute to normal motor
      learning and motor recovery after injury from multiple sclerosis.

PMID- 15145998
TI  - Elective stenting for symptomatic middle cerebral artery stenosis presenting as
      transient ischaemic deficits or stroke attacks: short term arteriographical and
      clinical outcome.
AB  - BACKGROUND: Although stent assisted angioplasty is an effective treatment for
      coronary and peripheral arterial disease, its efficacy in intracranial
      arteriosclerotic disease has not been verified. OBJECTIVES: To assess the
      radiographic and clinical outcome of stent assisted angioplasty for symptomatic
      middle cerebral artery (MCA) stenosis. METHODS: We attempted stent assisted
      angioplasty in 14 patients with symptomatic high grade stenosis (>60%) on the
      proximal portion of the MCA, who had experienced either recurrent transient
      ischaemic attacks (TIAs) resistant to medical therapy or one or more stroke
      attacks. Patient records were analysed for angiographic characteristics, degree
      of stenosis, pre-procedural regimen of anti-platelet and/or anti-coagulation
      agents, use of devices, procedure related complications, pre-operative and post
      operative single photon emission computed tomography (SPECT) findings, and
      clinical and radiographic outcomes. RESULTS: Stent assisted angioplasty was
      successfully performed in 8 of 14 patients without any serious complications and
      unsuccessful in 2 of 14 patients due to the tortuous curve of the internal
      carotid artery siphon. Four patients had complications. Two patients had an
      arterial rupture; one patient was rescued by an additional stent and balloon
      tamponade, the other patient died. Complications in the other two patients
      included thrombotic occlusion and distal thrombosis. Residual stenosis was less
      than 50% in diameter in all the patients. All eight patients who underwent follow
      up cerebral angiography had no restenosis. Follow up SPECT showed improved
      perfusion in the affected MCA territory in all the tested patients with TIA and
      in one of three stroke patients. Using the modified Rankin Scale at follow up,
      four of five TIA patients and five of six stroke patients were assessed as
      functionally improved or having a stable clinical status. CONCLUSION: Although
      the re-stenosis rate in stent assisted angioplasty seems to be better than in
      primary balloon angioplasty as reported previously, the complication rate is
      still high. Elective stenting is an alternative therapeutic method for the
      prevention of secondary ischaemic stroke in stroke patients with MCA stenosis,
      and seems to be a potentially effective but also hazardous therapeutic technique
      in patients with recurrent TIAs. This study indicates the need for randomised
      control trial data of this intervention. Additionally, long term follow up data
      and additional clinical experience are required to assess the durability of this
      procedure.

PMID- 15145999
TI  - Pneumonia in acute stroke patients fed by nasogastric tube.
AB  - BACKGROUND: Aspiration pneumonia is the most important acute complication of
      stroke related dysphagia. Tube feeding is usually recommended as an effective and
      safe way to supply nutrition in dysphagic stroke patients. OBJECTIVE: To estimate
      the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to
      determine risk factors for this complication, and to examine whether the
      occurrence of pneumonia is related to outcome. METHODS: Over an 18 month period a
      prospective study was done on 100 consecutive patients with acute stroke who were
      given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and
      artificial ventilation. Functional outcome was assessed at three months. Logistic
      regression and multivariate regression analyses were used, respectively, to
      identify variables significantly associated with the occurrence of pneumonia and
      those related to a poor outcome. RESULTS: Pneumonia was diagnosed in 44% of the
      tube fed patients. Most patients acquired pneumonia on the second or third day
      after stroke onset. Patients with pneumonia more often required endotracheal
      intubation and mechanical ventilation than those without pneumonia. Independent
      predictors for the occurrence of pneumonia were a decreased level of
      consciousness and severe facial palsy. The NIH stroke scale score on admission
      was the only independent predictor of a poor outcome. CONCLUSIONS: Nasogastric
      tubes offer only limited protection against aspiration pneumonia in patients with
      dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the
      illness and patients with decreased consciousness and a severe facial palsy are
      especially endangered.

PMID- 15146000
TI  - Clinical and radiological predictors of recanalisation and outcome of 40 patients
      with acute basilar artery occlusion treated with intra-arterial thrombolysis.
AB  - OBJECTIVE: To define predictors of recanalisation and clinical outcome of
      patients with acute basilar artery occlusions treated with local intra-arterial
      thrombolysis (IAT). METHODS: Vascular risk factors, severity of the neurological
      deficit graded by the National Institutes of Health stroke scale (NIHSS), and
      radiological findings were recorded at presentation. Outcome was measured using
      the modified Rankin scale (mRS) three months later and categorised as favourable
      (mRS 0-2), poor (mRS 3-5), or death (mRS 6). RESULTS: 40 patients were studied.
      Median NIHSS on admission was 18. Mean time from symptom onset to treatment was
      5.5 hours (range 2.3 to 11). Outcome was favourable in 14 patients (35%) and poor
      in nine (23%); 17 (42%) died. There were two symptomatic cerebral haemorrhages
      (5%). Recanalisation of the basilar artery was achieved in 32 patients (80%); it
      was complete (TIMI grade 3) in 20% and partial (TIMI grade 2) in 60%. In
      multivariate logistic regression analysis, low NIHSS score on admission (p =
      0.002) and vessel recanalisation (p = 0.005) were independent predictors of
      favourable outcome. Recanalisation occurred more often with treatment within six
      hours of symptom onset (p = 0.003) and when admission computed tomography showed
      a hyperdense basilar artery sign (p = 0.007). In a univariate model, quadriplegia
      (p = 0.002) and coma (p = 0.004) were associated with a poor outcome or death.
      CONCLUSIONS: Low baseline NIHSS on admission and recanalisation of basilar artery
      occlusions predict a favourable outcome after intra-arterial thrombolysis. Early
      initiation of IAT and the presence of a hyperdense basilar artery sign on CT were
      associated with a higher likelihood of recanalisation.

PMID- 15146001
TI  - Long term visual and neurological prognosis in patients with treated and
      untreated cavernous sinus aneurysms.
AB  - OBJECTIVE: To determine the long term visual and neurological outcome of patients
      diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up
      for at least five years or until death of 31 retrospectively recruited patients
      (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40
      aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median
      64). The most common symptoms were diplopia (61%), headache (53%), and facial or
      orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed
      cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus
      fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated
      symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from
      circulation, 10 shortly after diagnosis and 11 after worsening symptoms.
      Immediate complications of treatment occurred in six patients and included
      neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients
      (32%) were observed without intervention. Over a mean (SD) follow up period of
      11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and
      eight deteriorated. Among the 10 patients followed without intervention, none
      improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS:
      Most treated patients in this series improved or remained stable after treatment,
      but none improved without treatment. The long term prognosis for treated cases is
      relatively good, with most complications occurring immediately after the
      procedure. Endovascular surgery has decreased the morbidity and mortality of
      treatment so should be considered for any patient with a CCA.

PMID- 15146002
TI  - Does the method of treatment of acutely ruptured intracranial aneurysms influence
      the incidence and duration of cerebral vasospasm and clinical outcome?
AB  - OBJECTIVES: Cerebral vasospasm remains the leading cause of death and permanent
      disability after subarachnoid haemorrhage. This study determined whether the
      method of aneurysm treatment plays an important role in determining the incidence
      of cerebral vasospasm and its clinical consequences. METHODS: Admission data,
      cranial computed tomography (CT), treatment details, transcranial Doppler (TCD)
      results, and clinical outcomes of patients who had surgical or endovascular
      management of their ruptured aneurysm were recorded and subject to multivariate
      analysis. RESULTS: Between January 1995 and December 1999, 292 eligible patients
      (206 female, 86 male) had definitive aneurysm treatment at our unit. 212 patients
      were clipped, 80 coiled. There was no significant difference in patient age, pre
      treatment neurological grade, Fisher grade, or timing of treatment in the two
      groups. 48.3% patients developed TCD detected cerebral vasospasm and 16.1%
      patients developed permanent ischaemic neurological deficit. At clinical follow
      up, 84.2% of patients were well (mGOS 1 and 2) with a cumulative death rate of
      6.5% from all causes. The only significant predictor of TCD-detected cerebral
      vasospasm was patient age (inversely, p = 0.004). Increased patient age,
      vasospasm, poor pre-treatment WFNS, and higher CT Fisher grades correlated with a
      poor discharge GOS. However, only poor pre-treatment WFNS grade and patient age
      correlated with poor GOS at follow up (p<0.001). CONCLUSION: The treatment method
      had no influence on the incidence or duration of TCD detected vasospasm and there
      was no significant difference in outcome at discharge or follow up between those
      patients who had surgery or endovascular management of their aneurysms.

PMID- 15146004
TI  - Clinical features and long term outcome of epilepsy in periventricular nodular
      heterotopia. Simple compared with plus forms.
AB  - OBJECTIVES: Little is known about the long term outcome of patients with
      periventricular nodular heterotopia (PNH) and epilepsy, particularly the course
      of seizures. This study investigated the electroclinical and prognostic features
      of 16 patients with PNH. METHODS: Of 120 patients with epilepsy and malformations
      of cortical development, 16 had PNH. Of these, eight patients had periventricular
      nodules only (simple PNH) and eight also presented with other cortical or
      cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia;
      schizencephaly; cortical infolding; agenesis of the corpus callosum; mega
      cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent
      clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3
      years (2-40 years). RESULTS: Two electroclinical patterns emerged: (1) The first
      pattern, associated with simple PNH, was characterised by normal intelligence and
      seizures, usually partial, which began during the second decade of life. The
      seizures never became frequent and tended to disappear or become very rare. The
      EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus,
      was characterised by mental retardation and seizures that began during the first
      decade of life. The seizures were very frequent in most cases and sudden drops
      were observed in six patients. Seizures were medically refractory in four
      patients. The EEG showed focal and bisynchronous abnormalities. CONCLUSIONS: Two
      groups of PNH patients with different electroclinical and neuroradiological
      features can be identified after a long term follow up. The presence of other
      types of cortical or cerebral malformations, in addition to periventricular
      nodules, determines a poor prognosis.

PMID- 15146005
TI  - Localising and lateralising value of ictal piloerection.
AB  - BACKGROUND: Piloerection is a rare clinical symptom described during seizures.
      Previous reports suggested that the temporal lobe is the ictal onset zone in many
      of these cases. One case series concluded that there is a predominant left
      hemispheric representation of ictal cold. The aim of this study is to evaluate
      the localising and lateralising value of pilomotor seizures. METHODS: Medical
      records of patients who underwent video electroencephalogram (EEG) monitoring at
      the Cleveland Clinic between 1994 and 2001 were reviewed for the presence of
      ictal piloerection. The clinical history, physical and neurological examination,
      video EEG data, neuroimaging data, cortical stimulation results, and
      postoperative follow ups were reviewed and used to define the epileptogenic zone.
      Additionally, all previously reported cases of ictal piloerection were reviewed.
      RESULTS: Fourteen patients with ictal piloerection were identified (0.4%). Twelve
      out of 14 patients had temporal lobe epilepsy. In seven patients (50%), the ictal
      onset was located in the left hemisphere. Four out of five patients with
      unilateral ictal piloerection had ipsilateral temporal lobe epilepsy as compared
      with the ipsilateral side of pilomotor response. Three patients became seizure
      free after left temporal lobectomy for at least 12 months of follow up. An
      ipsilateral left leg pilomotor response with simultaneously recorded after
      discharges was elicited in one patient during direct cortical stimulation of the
      left parahippocampal gyrus. CONCLUSIONS: Ictal piloerection is a rare ictal
      manifestation that occurs predominantly in patients with temporal lobe epilepsy.
      Unilateral piloerection is most frequently associated with ipsilateral focal
      epilepsy. No hemispheric predominance was found in patients with bilateral ictal
      piloerection.

PMID- 15146006
TI  - Quantified measurement of activity provides insight into motor function and
      recovery in neurological disease.
AB  - BACKGROUND: A direct quantitative measurement of locomotor activity in an
      individual's own environment over an extended period may help in evaluating the
      impact of impairments in neurological disorders. OBJECTIVE: To investigate the
      reliability and validity of activity monitoring in neurological patients and
      healthy subjects. METHODS: Initial reliability studies were completed on 10
      healthy subjects and 10 mobility restricted neurological patients. Validity was
      investigated using 7 days of ambulatory monitoring with the Step Watch( step
      activity monitor, laboratory based measures of gait and the Rivermead Mobility
      Index (RMI) in 10 patients with multiple sclerosis, 10 with Parkinson's disease,
      and 10 with a primary muscle disorder. Additionally, 30 healthy subjects
      participated in the study. Two clinical illustrations of ambulatory monitoring
      are provided. RESULTS: The mean (range) right step count of 7 days of monitoring
      in both healthy and neurological patients proved a reliable measure of activity
      (intra-class correlations 0.89 and 0.86 respectively). The 7 day mean (range)
      right step count was 5951 (2886-9955) in healthy subjects, 3818 (1611-5391) in
      patients with Parkinson's disease, 3003 (716-5302) in those with muscular
      disorders, and 2985 (689-5340) in those with multiple sclerosis. A moderate
      correlation was noted between 7 day mean step count and gait speed (r = 0.45, p =
      0.01) in the grouped neurological patients but not the RMI (r(s) = 0.3, p =
      0.11). CONCLUSION: Ambulatory monitoring provides a reliable and valid measure of
      activity levels. Neurological patients, living independently, demonstrate lower
      activity levels than healthy matched controls. Ambulatory monitoring as an
      outcome measure has potential for improving the evaluation of ambulation and
      providing insight into participation.

PMID- 15146007
TI  - Correlation between clinical characteristics and proliferative activity in
      patients with craniopharyngioma.
AB  - OBJECTIVES: The aim of the study was to correlate the Ki-67 and cyclin A
      labelling index (LI) with clinical characteristics and risk of recurrence of
      craniopharyngiomas. METHODS: 47 consecutive patients were studied, 21 female and
      26 male, aged 34.3 (2.8) years. Immunohistochemical analysis was performed on
      paraffin wax embedded material using monoclonal antibodies directed against the
      proliferation associated nuclear antigen Ki-67 and cyclin A. RESULTS: The median
      Ki-67 LI was 8.6% (interquartile range, 4.4%-14.0%). Ki-67 LI was significantly
      higher in tumours with a heavy inflammatory reaction and diabetes insipidus at
      presentation, whereas other clinical and histological features were not
      associated with the proliferation index. There was a strong linear correlation
      between Ki-67 LI and cyclin A LI (r = 0.77; p<0.0001); therefore, cyclin A LI
      showed the same clinical and histological relations described for Ki-67 LI.
      Recurrence of craniopharyngioma occurred in 13 of 46 patients (28.3%). The median
      Ki-67 LI in the 13 recurrent craniopharyngiomas (9.0%) was not significantly
      different from that of non-recurring tumours (7.9%). Cyclin A LI was also not
      associated with the risk of relapse. CONCLUSIONS: This study confirms the great
      variability of proliferative activity in craniopharyngiomas. Ki-67 and cyclin A
      LIs were associated with the presence of a heavy inflammatory reaction and
      diabetes insipidus, but did not correlate with the long term risk of tumour
      regrowth.

PMID- 15146008
TI  - Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a
      lumbar puncture.
AB  - AIMS: The dural and arachnoid hole caused by lumbar puncture needles is a
      determining factor in triggering headaches. The aim of this study is to assess
      the dimensions and morphological features of the dura mater and arachnoids when
      they are punctured by a 22 gauge Quincke needle having its bevel either in the
      parallel or in the transverse position. METHODS: Fifty punctures were made with
      22 gauge Quincke needles in the dural sac of four fresh cadavers using an "in
      vitro" model especially designed for this purpose. The punctures were performed
      by needles with bevels parallel or perpendicular to the spinal axis and studied
      under scanning electron microscopy. RESULTS: Thirty five of the 50 punctures done
      by Quincke needles (19 in the external surface and 16 in the internal) were used
      for evaluation. When the needle was inserted with its bevel parallel to the axis
      of the dural sac (17 of 35), the size of the dura-arachnoid lesion was 0.032
      mm(2) in the epidural surface and 0.037 mm(2) in the subarachnoid surface of the
      dural sac. When the needle's bevel was perpendicular to the axis (18 of 35) the
      measurement of the lesion size was 0.042 mm(2) for the external surface and 0.033
      mm(2) for the internal. There were no statistical significant differences between
      these results. CONCLUSIONS: It is believed that the reported lower frequency of
      postdural puncture headache when the needle is inserted parallel to the cord axis
      should be explained by some other factors besides the size of the dura-arachnoid
      injury.

PMID- 15146009
TI  - Primary lateral sclerosis and Pierre Marie.

PMID- 15146010
TI  - Evolution of MRI changes and development of bilateral hippocampal sclerosis
      during long lasting generalised status epilepticus.
AB  - This report describes a previously healthy 28 year old patient with a 5 month
      period of intractable generalised status epilepticus (SE) of unknown aetiology
      with fatal outcome. Repeated magnetic resonance imaging (MRI) showed no pre
      existing abnormality, but did show progressive cortical and hippocampal atrophy
      and T2 hyperintensity in both hippocampal formations, suggestive of progressive
      tissue damage. Post-mortem histopathological analysis revealed substantial
      neuronal cell loss including CA1 and CA4 sectors of the hippocampus compatible
      with bilateral hippocampal sclerosis. There was no evidence of systemic
      complications including arterial hypotension and hypoxia, hypoglycaemia,
      hyperpyrexia, or other confounding factors to account for these findings. This
      case provides further evidence of SE induced hippocampal damage in humans.

PMID- 15146011
TI  - Number processing in temporal lobe epilepsy.
AB  - BACKGROUND: Specific cognitive impairments have been found in association with
      mesial temporal lobe epilepsy (TLE), such as deficits in declarative memory or
      verbal abilities. No attention has been paid so far to possible deficits in
      number processing. OBJECTIVE: To investigate deficits in number processing in
      patients with TLE. METHODS: Numerical abilities were assessed in 28 right handed
      patients with medically intractable unilateral TLE and in a control group.
      RESULTS: No differences between patients and controls were found in analogue
      number processing with Arabic input, in a comparison task, or in simple addition
      and simple subtraction; however, there were significant group differences in
      tasks with verbal input, in simple division, in complex mental calculation, in a
      semantic knowledge task, and in conceptual tasks. Only minor differences were
      found between patients with right and left TLE. CONCLUSIONS: While numerical
      deficits may be expected in patients with left sided TLE, it is open for
      discussion why patients with right sided TLE also show numerical deficits.

PMID- 15146013
TI  - Wilson's disease: diagnostic errors and clinical implications.
AB  - BACKGROUND: Therapeutic outcome of Wilson's disease (WD) significantly depends
      upon its early recognition. However, because of its rarity in community and
      protean manifestations, the diagnosis and treatment are often delayed. AIM: To
      ascertain diagnostic errors at initial evaluation in these patients. METHODS:
      Analysis of medical records of 307 patients of WD registered over 30 years was
      done regarding presenting manifestations, initial diagnostic omissions, and
      interval between onset of symptoms to diagnosis and treatment. RESULTS: Of the
      307 patients of WD diagnostic errors by referring doctors from different
      specialties of health care were detected in 192 patients. These were diverse and
      multiple and included schizophrenia, juvenile polyarthritis, rheumatic chorea,
      nephrotic syndrome, metachromatic leucodystrophy, congenital myopathies, subacute
      sclerosing panencephalitis, neurodegenerative disease among others. The mean (SD)
      delay was two (three) years (range: 0.08-30 years). Some of the interventions
      before establishment of correct diagnosis were electroconvulsive therapy,
      thalamotomy, antipsychotics, and surgical correction for bony deformity. While 98
      patients were referred with correct diagnosis, only 16 were given specific
      treatment. CONCLUSION: Awareness among health professionals about varied
      presenting features of WD and high index of suspicion may have prognostic
      implications.

PMID- 15146012
TI  - Motor overflow in Huntington's disease.
AB  - We investigated both motor overflow and ability to control voluntary movement in
      patients with Huntington's disease (HD). We hypothesised that, compared with
      controls, overflow would be significantly greater in HD participants and that
      they would exhibit poorer control of voluntary movement. In a finger flexion
      task, participants had to maintain target forces representing 25, 50, or 75% of
      the maximum strength capacity for whichever finger was performing the task;
      overflow was measured in the corresponding finger of the non-responding hand. HD
      participants exhibited significantly greater motor overflow than controls, and
      more difficulty controlling the target force with the active hand. In addition,
      the degree of overflow in HD participants positively correlated with overall
      UHDRS motor symptom severity. The presence of exacerbated motor overflow in HD,
      and its correlation with symptom severity, is an important finding worthy of
      further investigation.

PMID- 15146014
TI  - Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers'
      syndrome? An analysis of a national surveillance study.
AB  - BACKGROUND: There has been concern that children with variant Creutzfeldt-Jakob
      disease (vCJD) might be misdiagnosed as cases of Alpers' syndrome, as a
      spongiform degeneration of the brain is seen in both conditions. OBJECTIVE: To
      report a national prospective surveillance study of children with progressive
      intellectual and neurological deterioration, designed to detect any children in
      the United Kingdom with vCJD, to see whether this misdiagnosis is occurring.
      METHODS: A monthly surveillance card is sent by the British Paediatric
      Surveillance Unit to all consultant paediatricians in the UK. The card lists the
      disorders currently under surveillance. Paediatricians are asked to return the
      card, reporting cases seen in the previous month. The BPSU office informs the
      surveillance groups about reported cases, and they obtain clinical information
      from the notifying paediatrician. RESULTS: After 5 years and 8 months of
      surveillance, 1244 children had been reported to the study. Alpers' syndrome was
      confirmed in two, although this was the suggested diagnosis in 11 children at the
      time of initial notification. CONCLUSIONS: The results show that Alpers' syndrome
      is rare and it is unlikely that vCJD cases are being misdiagnosed as Alpers'
      syndrome.

PMID- 15146016
TI  - Sporadic inclusion body myositis: morphology, regeneration, and cytoskeletal
      structure of muscle fibres.
AB  - OBJECTIVE: To characterise morphological abnormalities in relation to muscle
      fibre type in sporadic inclusion body myositis (s-IBM). METHODS: 14 muscle
      biopsies from 11 patients with s-IBM were characterised for morphological
      abnormalities and fibre type composition as well as muscle fibre regeneration and
      cytoskeletal structure, using histochemical and immunohistochemical techniques.
      RESULTS: Morphological abnormalities included inflammatory infiltrates and
      "rimmed vacuoles," and pronounced variation in fibre size. There were no
      significant differences in fibre type composition between s-IBM patients and
      controls based on the myofibrillar ATPase staining. A differential effect on
      muscle fibre sizes was noted, type II fibres being smaller in the s-IBM patients
      than in the controls. Conversely, the mean type I muscle fibre diameter in the s
      IBM patients was larger than in the controls, though this difference was not
      significant. An ongoing intense regeneration process was present in s-IBM muscle,
      as indicated by the expression of neonatal myosin heavy chain, vimentin, and CD56
      (Leu-19) in most of the muscle fibres. The cytoskeletal proteins dystrophin and
      desmin were normally expressed in s-IBM muscle fibres that were not undergoing
      degeneration or regeneration. CONCLUSIONS: There are extensive morphological and
      morphometric alterations in s-IBM, affecting different muscle fibre types in
      different ways. The cytoskeletal structure of type I and II muscle fibres remains
      unaffected in different stages of the disease.

PMID- 15146015
TI  - A dystonic syndrome associated with anti-basal ganglia antibodies.
AB  - Anti-basal ganglia antibodies (ABGA) have been associated with movement disorders
      (usually tics and chorea) and psychiatric disturbance in children. This report
      describes five adult and adolescent patients (one male, four females; mean age of
      onset, 16 years (range, 13-35)) who presented subacutely with a clinical syndrome
      dominated by dystonia and had ABGA binding to antigens of similar molecular
      weights to those seen in Sydenham's chorea. Three patients had a clear history of
      respiratory infection before the onset of their symptoms. Three patients received
      immunosuppressive treatment, with three showing a notable reduction in symptoms.
      It is hypothesised that dystonia in adults or adolescents may be part of the
      clinical spectrum of the post-infectious syndrome associated with ABGA.

PMID- 15146017
TI  - Pseudobulbar crying induced by stimulation in the region of the subthalamic
      nucleus.
AB  - We describe a case of pseudobulbar crying associated with deep brain stimulation
      (DBS) in the region of the subthalamic nucleus (STN). Patients with pseudobulbar
      crying show no other evidence of subjective feelings of depression such as
      dysphoria, anhedonia, or vegetative signs. This may be accompanied by other
      symptoms of pseudobulbar palsy and has been reported to occur with ischaemic or
      structural lesions in both cortical and subcortical regions of the brain.
      Although depression has been observed to result from DBS in the region of the
      STN, pseudobulbar crying has not been reported. A single patient who reported the
      symptoms of pseudobulbar crying after placement of an STN DBS was tested in the
      off DBS and on DBS conditions. The patient was tested using all four DBS lead
      contacts and the observations and results of the examiners were recorded. The
      Geriatric Depression Scale was used to evaluate for depression in all of the
      conditions. The patient exhibited pseudobulbar crying when on monopolar
      stimulation at all four lead contacts. The pseudobulbar crying resolved off
      stimulation. This case describes another type of affective change that may be
      associated with stimulation in the region of or within the STN. Clinicians should
      be aware of this potential complication, the importance of differentiating it
      from stimulation induced depression, and its response to a serotonin reuptake
      inhibitor, such as sertraline.

PMID- 15146018
TI  - Probable multiple system atrophy in a German family.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown
      aetiology. A possible underlying genetic component has not yet been identified. A
      family is reported with phenotypic MSA and probable autosomal dominant
      inheritance. The patients presented initially with either parkinsonian or
      cerebellar signs, and developed severe autonomic failure and typical atrophy of
      the brain stem and cerebellum in the course of the disease.

PMID- 15146019
TI  - Detection of cerebral perfusion abnormalities in acute stroke using phase
      inversion harmonic imaging (PIHI): preliminary results.
AB  - Phase inversion harmonic imaging (PIHI) with newer contrast agents can display
      parameters of cerebral perfusion either using the established ipsilateral
      approach, or the novel bilateral approach in which both hemispheres are assessed
      in one examination. The aim of this study was to evaluate the potential of PIHI
      in detecting pathological perfusion in acute stroke, using the bilateral
      approach. Patients with a hemispheric syndrome presenting within 12 hours after
      symptom onset were examined with PIHI (SonoVue; bolus kinetics, fitted model
      function) using the bilateral approach if possible. Semi-quantitative perfusion
      related parameters (time to peak intensity (TPI) and peak width (PW)) were
      evaluated, and results correlated to follow up cerebral computed tomography (CCT)
      scans. In these four preliminary cases (one ipsilateral, three bilateral), PIHI
      was able to identify the ischaemic region because the function could not be
      fitted to the data. In one case, there was a difference between a core region
      where no perfusion was seen, and a surrounding region where hypoperfusion was
      detected (prolonged TPI and reduced PW). PIHI was able to predict the
      localisation and size of the eventual infarction even if no early CCT signs were
      seen. Furthermore, in one case, a surrounding hypoperfused region was identified,
      where tissue survived after recanalisation of the initially occluded middle
      cerebral artery. Using the bilateral approach, two advantages in comparison with
      the ipsilateral approach were obvious: cortical structures could be evaluated,
      and only one examination was needed to compare unaffected (ipsilateral) with
      affected (contralateral) tissue. These results should be confirmed by more cases,
      and should also be correlated to acute perfusion/diffusion weighted MRI data.

PMID- 15146021
TI  - The Kinnier Wilson library in Edinburgh.

PMID- 15146022
TI  - Organophosphate poisoning case with atypical clinical survey and magnetic
      resonance imaging findings.

PMID- 15146020
TI  - DNA end labelling (TUNEL) in a 3 year old girl with Leigh syndrome and prevalent
      cortical involvement.
AB  - Neuropathological study of a 3 1/2 year old girl with familial Leigh syndrome who
      also harboured a rare ATPase gene mutation disclosed extensive and unusual
      lesions in the cerebral cortex, despite a typical histological pattern. Early
      lesions in the periacqueductal grey matter of the brainstem, characterised by
      capillary congestion and initial regressive neuronal changes, were also observed,
      along with TUNEL reactive neuronal cells showing morphological signs typical of
      apoptosis in cortical areas with neuronal cell loss. The finding of lesions in
      atypical brain areas and for the first time, very early regressive neuronal
      phenomena, suggest that early changes in crucial brain areas may have been a
      cause of death. The abundance of TUNEL positive nuclei in cortical areas in the
      present case suggests that the apoptosis may be involved in the mechanism of
      neuronal death in Leigh syndrome.

PMID- 15146024
TI  - Pre-treatment with corticosteroids and a single cycle of high dose albendazole
      for subarachnoidal cysticercosis.

PMID- 15146023
TI  - Coincidence of a large SCA12 repeat allele with a case of Creutzfeld-Jacob
      disease.

PMID- 15146025
TI  - Short term benefit of battery depletion in vagus nerve stimulation for epilepsy.

PMID- 15146026
TI  - The aetiology of flaccid paralysis in West Nile virus infection.

PMID- 15146027
TI  - Spontaneous retinal venous pulsations can be present with a swollen optic disc.

PMID- 15146028
TI  - XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1
      cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis,
      enzymatic conversion to gabapentin, and transport by intestinal solute
      transporters.
AB  - Gabapentin is thought to be absorbed from the intestine of humans and animals by
      a low-capacity solute transporter localized in the upper small intestine.
      Saturation of this transporter at doses used clinically leads to dose-dependent
      pharmacokinetics and high interpatient variability, potentially resulting in
      suboptimal drug exposure in some patients. XP13512 [(+/-)-1-([(alpha
      isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid] is a novel
      prodrug of gabapentin designed to be absorbed throughout the intestine by high
      capacity nutrient transporters. XP13512 was stable at physiological pH but
      rapidly converted to gabapentin in intestinal and liver tissue from rats, dogs,
      monkeys, and humans. XP13512 was not a substrate or inhibitor of major cytochrome
      P450 isoforms in transfected baculosomes or liver homogenates. The separated
      isomers of XP13512 showed similar cleavage in human tissues. The prodrug
      demonstrated active apical to basolateral transport across Caco-2 cell monolayers
      and pH-dependent passive permeability across artificial membranes. XP13512
      inhibited uptake of (14)C-lactate by human embryonic kidney cells expressing
      monocarboxylate transporter type-1, and direct uptake of prodrug by these cells
      was confirmed using liquid chromatography-tandem mass spectrometry. XP13512
      inhibited uptake of (3)H-biotin into Chinese hamster ovary cells overexpressing
      human sodium-dependent multivitamin transporter (SMVT). Specific transport by
      SMVT was confirmed by oocyte electrophysiology studies and direct uptake studies
      in human embryonic kidney cells after tetracycline-induced expression of SMVT.
      XP13512 is therefore a substrate for several high-capacity absorption pathways
      present throughout the intestine. Therefore, administration of the prodrug should
      result in improved gabapentin bioavailability, dose proportionality, and colonic
      absorption compared with administration of gabapentin.

PMID- 15146029
TI  - XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1
      cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral
      bioavailability, dose proportionality, and colonic absorption compared with
      gabapentin in rats and monkeys.
AB  - The absorption of gabapentin (Neurontin) is dose-dependent and variable between
      patients. Rapid clearance of the drug necessitates dosing three or more times per
      day to maintain therapeutic levels. These deficiencies appear to result from the
      low capacity, limited intestinal distribution, and variable expression of the
      solute transporter responsible for gabapentin absorption. Saturation of this
      transporter at doses used clinically leads to unpredictable drug exposure and
      potentially ineffective therapy in some patients. XP13512 [(+/-)-1-([(alpha
      isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexane acetic acid] is a novel
      prodrug of gabapentin designed to be absorbed by high-capacity nutrient
      transporters located throughout the intestine. XP13512 was efficiently absorbed
      and rapidly converted to gabapentin after oral dosing in rats and monkeys.
      Exposure to gabapentin was proportional to prodrug dose, whereas exposure to
      intact XP13512 was low. In rats, >95% of an oral dose of (14)C-XP13512 was
      excreted in urine in 24 h as gabapentin. In monkeys, oral bioavailability of
      gabapentin from XP13512 capsules was 84.2% compared with 25.4% after a similar
      oral Neurontin dose. Compared with intracolonic gabapentin, intracolonic XP13512
      gave a 17-fold higher gabapentin exposure in rats and 34-fold higher in monkeys.
      XP13512 may therefore be incorporated into a sustained release formulation to
      provide extended gabapentin exposure. XP13512 demonstrated improved gabapentin
      bioavailability, increased dose proportionality, and enhanced colonic absorption.
      In clinical use, XP13512 may improve the treatment of neuropathic pain, epilepsy,
      and numerous other conditions by increasing efficacy, reducing interpatient
      variability, and decreasing frequency of dosing.

PMID- 15146030
TI  - Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2
      (4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea
      sulfate salt): first demonstration of a pathophysiological role of the urotensin
      System.
AB  - Urotensin-II (U-II) is a cyclic peptide now described as the most potent
      vasoconstrictor known. U-II binds to a specific G protein-coupled receptor,
      formerly the orphan receptor GPR14, now renamed urotensin receptor (UT receptor),
      and present in mammalian species. Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy
      piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new
      potent and specific antagonist of the human UT receptor. ACT-058362 antagonizes
      the specific binding of (125)I-labeled U-II on natural and recombinant cells
      carrying the human UT receptor with a high affinity in the low nanomolar range
      and a competitive mode of antagonism, revealed only with prolonged incubation
      times. ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen
      activated protein kinase phosphorylation. The binding inhibitory potency of ACT
      058362 is more than 100-fold less on the rat than on the human UT receptor, which
      is reflected in a pD'(2) value of 5.2 for inhibiting contraction of isolated rat
      aortic rings induced by U-II. In functional assays of short incubation times, ACT
      058362 behaves as an apparent noncompetitive inhibitor. In vivo, intravenous ACT
      058362 prevents the no-reflow phenomenon, which follows renal artery clamping in
      rats, without decreasing blood pressure and prevents the subsequent development
      of acute renal failure and the histological consequences of ischemia. In
      conclusion, the in vivo efficacy of the specific UT receptor antagonist ACT
      058362 reveals a role of endogenous U-II in renal ischemia. As a selective renal
      vasodilator, ACT-058362 may be effective in other renal diseases.

PMID- 15146031
TI  - The serotonin1A receptor partial agonist S15535 [4-(benzodioxan-5-yl)1-(indan-2
      yl)piperazine] enhances cholinergic transmission and cognitive function in
      rodents: a combined neurochemical and behavioral analysis.
AB  - These studies examined the influence of the selective 5-hydroxytryptamine
      (serotonin) (5-HT)(1A) receptor partial agonist S15535 [4-(benzodioxan-5-yl)1
      (indan-2-yl)piperazine] upon cholinergic transmission and cognitive function in
      rodents. In the absence of acetylcholinesterase inhibitors, S15535 dose
      dependently (0.04-5.0 mg/kg s.c.) elevated dialysis levels of acetylcholine in
      the frontal cortex and dorsal hippocampus of freely moving rats. In the cortex,
      the selective 5-HT(1A) receptor antagonist WAY100,635 [(N-[2-[4-(2-methoxyphenyl)
      1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide) fumarate] dose
      dependently (0.0025-0.63) blocked this action of S15535. By contrast, in dorsal
      hippocampus, WAY100,635 mimicked the induction of acetylcholine release by
      S15535. In a social recognition paradigm, S15535 dose-dependently (0.16-10.0)
      improved retention, an action blocked by WAY100,635 (0.16), which was ineffective
      alone. Furthermore, S15535 dose-dependently (0.04-2.5) and WAY100,635 reversibly
      abolished amnesic properties of the muscarinic antagonist scopolamine (0.63) in
      this procedure. Cognitive deficits provoked by scopolamine in autoshaping and
      Morris water-maze procedures were likewise blocked by S15535 at doses of 0.63 to
      10.0 and 0.16 to 2.5, respectively. In a two-platform spatial discrimination
      task, in which S15535 similarly abrogates cognitive deficits elicited by
      scopolamine, injection of S15535 (1.0 and 10.0 microg) into dorsal hippocampus
      blocked amnesic effects of the 5-HT(1A) agonist 8-hydroxy-2-dipropylaminotetralin
      (0.5 microg). Finally, S15535 (0.16-0.63) improved performance in a spatial,
      delayed nonmatching to sample model in mice, and in an operant delayed
      nonmatching to sample model in old rats, S15535 (1.25-5.0 mg/kg p.o.) increased
      response accuracy and reduced latency to respond. In conclusion, S15535
      reinforces frontocortical and hippocampal release of acetylcholine and displays a
      broad-based pattern of procognitive properties. Its actions involve both blockade
      of postsynaptic 5-HT(1A) receptors and engagement of 5-HT(1A) autoreceptors.

PMID- 15146034
TI  - Brain tumours: incidence, survival, and aetiology.

PMID- 15146035
TI  - Overview: Brain tumour diagnosis and management/Royal College of Physicians
      guidelines.

PMID- 15146036
TI  - The present and future management of malignant brain tumours: surgery,
      radiotherapy, chemotherapy.

PMID- 15146033
TI  - Brain tumours: classification and genes.

PMID- 15146037
TI  - The dilemma of low grade glioma.

PMID- 15146038
TI  - Overview of the diagnosis and management of brain, spine, and meningeal
      metastases.

PMID- 15146039
TI  - Paraneoplastic syndromes: when to suspect, how to confirm, and how to manage.

PMID- 15146040
TI  - Thermoeffector neuronal pathways in fever: a study in rats showing a new role of
      the locus coeruleus.
AB  - It is known that brain noradrenaline (norepinephrine) mediates fever, but the
      neuronal group involved is unknown. We studied the role of the major
      noradrenergic nucleus, the locus coeruleus (LC), in lipopolysaccharide (LPS)
      induced fever. Male Wistar rats had their LC completely ablated electrolytically
      or their catecholaminergic LC neurones selectively lesioned by microinjection of
      6-hydroxydopamine; the controls were sham-operated. Both lesions resulted in a
      marked attenuation of LPS (1 or 10 microg kg(-1), i.v.) fever at a subneutral (23
      degrees C) ambient temperature (Ta). Because electrolytic and chemical lesions
      produced similar effects, the role of the LC in fever was further investigated
      using electrolytic lesions only. The levels of prostaglandin (PG) E2, the
      terminal mediator of fever, were equally raised in the anteroventral third
      ventricular region of LC-lesioned and sham-operated rats during the course of LPS
      fever, indicating that LC neurones are not involved in febrigenic signalling to
      the brain. To investigate the potential involvement of the LC in an efferent
      thermoregulatory neuronal pathway, the thermoregulatory response to PGE(2) (25
      ng, i.c.v.) was studied at a subneutral (23 degrees C, when fever is brought
      about by thermogenesis) or neutral (28 degrees C, when fever is brought about by
      tail skin vasoconstriction) Ta. The PGE2-induced increases in metabolic rate (an
      index of thermogenesis) and fever were attenuated in LC-lesioned rats at 23
      degrees C, whereas PGE2-induced skin vasoconstriction and fever normally
      developed in LC-lesioned rats at 28 degrees C. The LC-lesioned rats had
      attenuated PGE2 thermogenesis despite the fact that they were fully capable of
      activating thermogenesis in response to noradrenaline and cold exposure. It is
      concluded that LC neurones are part of a neuronal network that is specifically
      activated by PGE2 to increase thermogenesis and produce fever.

PMID- 15146041
TI  - Neuroactive steroids have multiple actions to potentiate GABAA receptors.
AB  - The effects of neuroactive steroids on the function of GABAA receptors were
      studied using cell-attached records of single channel activity recorded from
      HEK293 cells transfected with alpha1 beta2 gamma2L subunits. Activity was
      elicited with a half-maximal (50 microM) concentration of GABA. Two steroids were
      studied in detail: ACN ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17
      carbonitrile) and B285 ((3alpha,5beta,17beta)-3-hydroxy-18-norandrostane-17
      carbonitrile). Four effects on channel activity were seen, two on open time
      distributions and two on closed times. When clusters of openings were elicited in
      the absence of steroid, the open time distribution contained three components.
      ACN produced concentration-dependent alterations in the open time distribution.
      The prevalence of the longest duration class of open times was increased from
      about 15% to about 40% (EC50 about 180 nM ACN), while the duration of the longest
      class increased from 7.4 ms to 27 ms (EC50 about 35 nM ACN). B285 also increased
      the prevalence of the longest duration open times (EC50 about 18 nM B285) but
      increased the duration only at concentrations close to 10 microM. The differences
      in the actions of these two steroids suggest that the effects on proportion and
      duration of the long duration open time component are produced by independent
      mechanisms and that there are separate recognition sites for the steroids which
      are associated with the two functional actions. The closed time distributions
      also showed three components in the absence of steroid. The rate of occurrence of
      the two brief duration closed time components decreased with increasing ACN, with
      an EC50 of about 50 nM ACN. In contrast, B285 did not reduce the rate of
      occurrence of the brief closings until high concentrations were applied. However,
      both B285 and ACN reduced the rate of occurrence of the activation-related closed
      state selectively, with comparable IC50 concentrations (about 40 nM ACN, 20 nM
      B285). As in the case for action on open times these data suggest that there are
      two recognition sites and two independent mechanisms, perhaps the sites and
      mechanisms associated with actions on open times. The presence of 1 microM ACN
      had no effect on the estimated channel opening rate or on the apparent affinity
      of the receptor for GABA. Mutation of the carboxy terminus of the gamma2 subunit,
      but not the alpha1 or beta2 subunits, abolished the ability of ACN to increase
      the duration of OT3 but had no effect on the reduction of the rate of occurrence
      of the activation-related closed state. These observations are also consistent
      with the idea that there is more than one distinguishable steroid recognition
      site on the GABAA receptor.

PMID- 15146042
TI  - The mammalian amiloride-insensitive non-specific salt taste receptor is a
      vanilloid receptor-1 variant.
AB  - The amiloride-insensitive salt taste receptor is the predominant transducer of
      salt taste in some mammalian species, including humans. The physiological,
      pharmacological and biochemical properties of the amiloride-insensitive salt
      taste receptor were investigated by RT-PCR, by the measurement of unilateral
      apical Na+ fluxes in polarized rat fungiform taste receptor cells and by chorda
      tympani taste nerve recordings. The chorda tympani responses to NaCl, KCl, NH4Cl
      and CaCl2 were recorded in Sprague-Dawley rats, and in wild-type and vanilloid
      receptor-1 (VR-1) knockout mice. The chorda tympani responses to mineral salts
      were monitored in the presence of vanilloids (resiniferatoxin and capsaicin), VR
      1 antagonists (capsazepine and SB-366791), and at elevated temperatures. The
      results indicate that the amiloride-insensitive salt taste receptor is a
      constitutively active non-selective cation channel derived from the VR-1 gene. It
      accounts for all of the amiloride-insensitive chorda tympani taste nerve response
      to Na+ salts and part of the response to K+, NH4+ and Ca2+ salts. It is activated
      by vanilloids and temperature (> 38 degrees C), and is inhibited by VR-1
      antagonists. In the presence of vanilloids, external pH and ATP lower the
      temperature threshold of the channel. This allows for increased salt taste
      sensitivity without an increase in temperature. VR-1 knockout mice demonstrate no
      functional amiloride-insensitive salt taste receptor and no salt taste
      sensitivity to vanilloids and temperature. We conclude that the mammalian non
      specific salt taste receptor is a VR-1 variant.

PMID- 15146043
TI  - Response of human cells to desiccation: comparison with hyperosmotic stress
      response.
AB  - Increasing interest in anhydrobiosis ('life without water') has prompted the use
      of mammalian cells as a model in which candidate adaptations suspected of
      conferring desiccation tolerance can be tested. Despite this, there is no
      information on whether mammalian cells are able to sense and respond to
      desiccation. We have therefore examined the effect of desiccation on stress
      signalling pathways and on genes which are proposed to be expressed in response
      to water loss through osmotic stress. Depending on the severity of the drying
      regime, human cells survived for at least 24 h. Both SAPK/JNK and p38 mitogen
      activated protein kinases (MAPKs) were activated within 30 min by desiccation as
      well as by all osmotica tested, and therefore MAPK pathways probably play an
      important role in both responses. Gene induction profiles differed under the two
      stress conditions, however: quantitative polymerase chain reaction (PCR)
      experiments showed that AR, BGT-1 and SMIT, which encode proteins governing
      organic osmolyte accumulation, were induced by hypersalinity but not by
      desiccation. This was surprising, since these genes have been proposed to be
      regulated by ionic strength and cell volume, both of which should be
      significantly affected in drying cells. Further investigation demonstrated that
      AR, BGT-1 and SMIT expression was dependent on the nature of the osmolyte. This
      suggests that their regulation involves factors other than intracellular ionic
      strength and cell volume changes, consistent with the lack of induction by
      desiccation. Our results show for the first time that human cells react rapidly
      to desiccation by MAPK activation, and that the response partially overlaps with
      that to hyperosmotic stress.

PMID- 15146044
TI  - Desensitization of the mGluR6 transduction current in tiger salamander On bipolar
      cells.
AB  - Light depolarizes retinal On bipolar cells, opening the cation-selective channels
      that are responsible for producing the synaptic current. In this study, the basic
      features of light-induced signals were mimicked by bathing slices of salamander
      retina with an agonist for the mGluR6 receptor that is expressed on the dendrites
      of On cells, and then displacing the agonist with the mGluR6 antagonist (RS)-a
      cyclopropyl-4-phosphonophenylglycine (CPPG). The transduction current that is
      activated by this protocol rapidly shuts off, or desensitizes. Desensitization
      was highly correlated with the concentration and the type of Ca2+ buffer that was
      dialysed into the cell: When Ca2+ buffering was minimized by dialysing cells with
      0.5 mM EGTA, the steady-state response was reduced to approximately 40% of the
      peak response. Buffering with 10 mM EGTA reduced desensitization, while BAPTA
      completely eliminated it. Removing external Ca2+ also prevented desensitization,
      suggesting that entry of Ca2+ through the transduction channel provides the
      trigger. The time course of desensitization was measured by using a voltage jump
      protocol to rapidly increase Ca2+ influx, and could be fitted with a single time
      constant on the order of 1 s, in good agreement with previously published rates
      of desensitization to steps of light in this species. It is proposed that Ca(2+)
      dependent shut-off of the On bipolar cell transduction current may contribute to
      the conversion of sustained to transient light responses that predominate in the
      inner retina.

PMID- 15146045
TI  - M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic
      control of salivation in mice.
AB  - The M(1) and M(3) subtypes are the major muscarinic acetylcholine receptors in
      the salivary gland and M(3) is reported to be more abundant. However, despite
      initial reports of salivation abnormalities in M(3)-knockout (M(3)KO) mice, it is
      still unclear which subtype is functionally relevant in physiological salivation.
      In the present study, salivary secretory function was examined using mice lacking
      specific subtype(s) of muscarinic receptor. The carbachol-induced [Ca(2+)](i)
      increase was markedly impaired in submandibular gland cells from M(3)KO mice and
      completely absent in those from M(1)/M(3)KO mice. This demonstrates that M(3) and
      M(1) play major and minor roles, respectively, in the cholinergically induced
      [Ca(2+)](i) increase. Two-dimensional Ca(2+)-imaging analysis revealed the patchy
      distribution of M(1) in submandibular gland acini, in contrast to the ubiquitous
      distribution of M(3). In vivo administration of a high dose of pilocarpine (10 mg
      kg(-1), s.c.) to M(3)KO mice caused salivation comparable to that in wild-type
      mice, while no salivation was induced in M(1)/M(3)KO mice, indicating that
      salivation in M(3)KO mice is caused by an M(1)-mediated [Ca(2+)](i) increase. In
      contrast, a lower dose of pilocarpine (1 mg kg(-1), s.c.) failed to induce
      salivation in M(3)KO mice, but induced abundant salivation in wild-type mice,
      indicating that M(3)-mediated salivation has a lower threshold than M(1)-mediated
      salivation. In addition, M(3)KO mice, but not M(1)KO mice, had difficulty in
      eating dry food, as shown by frequent drinking during feeding, suggesting that
      salivation during eating is mediated by M(3) and that M(1) plays no practical
      role in it. These results show that the M(3) subtype is essential for
      parasympathetic control of salivation and a reasonable target for the drug
      treatment and gene therapy of xerostomia, including Sjogren's syndrome.

PMID- 15146046
TI  - Global dendritic calcium spikes in mouse layer 5 low threshold spiking
      interneurones: implications for control of pyramidal cell bursting.
AB  - Interneuronal networks in neocortex underlie feedforward and feedback inhibition
      and control the temporal organization of pyramidal cell activity. We previously
      found that lower layer neocortical interneurones can reach action potential
      threshold in response to the stimulation of a single presynaptic cell. To better
      understand this phenomenon and the circuit roles of lower layer neocortical
      interneurones, we combined two-photon calcium imaging with whole cell recordings
      and anatomical reconstructions of low threshold spiking (LTS) interneurones from
      mouse neocortex. In both visual and somatosensory cortex, LTS interneurones are
      somatostatin-positive, concentrated in layer 5 and possess dense axonal
      innervation to layer 1. Due to the LTS properties, these neurones operate in
      burst and tonic modes. In burst mode, dendritic T-type calcium channels boosted
      small synaptic inputs and triggered low threshold calcium spikes, while in tonic
      mode, sodium-based APs evoked smaller calcium influxes. In both modes, the entire
      dendritic tree of LTS interneurones behaved as a 'global' single spiking unit.
      This, together with the fact that synaptic inputs to layer 5 LTS cells are
      facilitating, and that their axons target the dendritic region of the pyramidal
      neurones where bursts are generated, make these neurones ideally suited to detect
      and control burst generation of individual lower layer pyramidal neurones.

PMID- 15146048
TI  - Differences in activity-dependent hyperpolarization in human sensory and motor
      axons.
AB  - The present study was undertaken to determine whether activity-dependent changes
      in axonal excitability are greater in motor axons than cutaneous afferents for
      the same impulse load. In nine healthy subjects, supramaximal stimulation at 8 Hz
      was delivered to the median nerve at the wrist. Changes in the threshold current
      required to generate compound motor and sensory potentials approximately 50% of
      maximum and other indices of axonal excitability were tracked before and after
      repetitive stimulation for 10 min. The long-lasting stimulation produced a
      prolonged depression in the excitability of both cutaneous afferents and motor
      axons, with gradual recovery to control levels over 15-20 min. These changes in
      threshold were associated with a reduction in refractoriness, an increase in
      supernormality and a decrease in the strength-duration time constant, changes
      consistent with axonal hyperpolarization. Greater changes in threshold occurred
      in motor axons: threshold increased by 9.9% and 16.4% for test stimulus durations
      of 0.1 and 1 ms, respectively, for motor axons and by 5.4% and 8.3% for cutaneous
      afferents. With higher stimulus frequencies and thereby greater impulse loads,
      greater threshold changes could be induced in cutaneous afferents. It is argued
      that the hyperpolarization resulted from activity of the electrogenic Na(+)-K+
      pump, that it requires > 125 ms to restore the resting state following an action
      potential, and that significant intracellular Na+ accumulation occurs during a
      steady 8-Hz train. These findings imply that physiological discharge rates will
      activate the pump and thereby produce axonal hyperpolarization, the extent of
      which will vary with impulse load. A plausible explanation is that greater
      activity-dependent hyperpolarization in motor axons is due to less inward
      rectification as a result of less activity of the hyperpolarization-activated
      cation conductance (IH) than in cutaneous afferents.

PMID- 15146047
TI  - Phasic spike patterning in rat supraoptic neurones in vivo and in vitro.
AB  - In vivo, most vasopressin cells of the hypothalamic supraoptic nucleus fire
      action potentials in a 'phasic' pattern when the systemic osmotic pressure is
      elevated, while most oxytocin cells fire continuously. The phasic firing pattern
      is believed to arise as a consequence of intrinsic activity-dependent changes in
      membrane potential, and these have been extensively studied in vitro. Here we
      analysed the discharge patterning of supraoptic nucleus neurones in vivo, to
      infer the characteristics of the post-spike sequence of hyperpolarization and
      depolarization from the observed spike patterning. We then compared patterning in
      phasic cells in vivo and in vitro, and we found systematic differences in the
      interspike interval distributions, and in other statistical parameters that
      characterized activity patterns within bursts. Analysis of hazard functions
      (probability of spike initiation as a function of time since the preceding spike)
      revealed that phasic firing in vitro appears consistent with a regenerative
      process arising from a relatively slow, late depolarizing afterpotential that
      approaches or exceeds spike threshold. By contrast, in vivo activity appears to
      be dominated by stochastic rather than deterministic mechanisms, and appears
      consistent with a relatively early and fast depolarizing afterpotential that
      modulates the probability that random synaptic input exceeds spike threshold.
      Despite superficial similarities in the phasic firing patterns observed in vivo
      and in vitro, there are thus fundamental differences in the underlying
      mechanisms.

PMID- 15146049
TI  - Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape 'superslow'
      afterburst EPSC in rat hippocampus.
AB  - In conditions of facilitated synaptic release, CA3/CA1 synapses generate
      anomalously slow NMDA receptor-mediated EPSCs (EPSC(NMDA)). Such a time course
      has been attributed to the cooperation of synapses through glutamate spillover.
      Imitating a natural pattern of activity, we have applied short bursts (2-7
      stimuli) of high-frequency stimulation and observed a spike-to-spike slow-down of
      the EPSC(NMDA) kinetics, which accompanied synaptic facilitation. It was found
      that the early component of the EPSC(NMDA) and the burst-induced late component
      of the EPSC(NMDA) have distinct pharmacological properties. The competitive NMDA
      antagonist R-(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (D-CPP),
      which has higher affinity to NR2A than to NR2B subunits and lowest affinity at
      NR2D subunits, significantly slowed down the decay rate of the afterburst EPSC
      while leaving the kinetics of the control current unaffected. In contrast,
      ifenprodil, a highly selective NR2B antagonist, and [+/-]-cis-1-[phenanthren-2yl
      carbonyl]piperazine-2,3-dicarboxylic acid (PPDA), a competitive antagonist that
      is moderately selective for NR2D subunits, more strongly inhibited the late
      component of the afterburst EPSC(NMDA). The receptors formed by NR2B and
      (especially) NR2D subunits are known to have higher agonist sensitivity and much
      slower deactivation kinetics than NR2A-containing receptors. Furthermore, NR2B is
      preferentially and NR2D is exclusively located on extrasynaptic membranes. As the
      density of active synapses increases, the confluence of released glutamate makes
      EPSC decay much longer by activating more extrasynaptic NR2B- and NR2D-subunit
      containing receptors. Long-term potentiation (LTP) induced by successive rounds
      of burst stimulation is accompanied by a long-term increase in the contribution
      of extrasynaptic receptors in the afterburst EPSC(NMDA.)

PMID- 15146050
TI  - Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance
      after cold adaptation of king penguins.
AB  - Juvenile king penguins develop adaptive thermogenesis after repeated immersion in
      cold water. However, the mechanisms of such metabolic adaptation in birds are
      unknown, as they lack brown adipose tissue and uncoupling protein-1 (UCP1), which
      mediate adaptive non-shivering thermogenesis in mammals. We used three different
      groups of juvenile king penguins to investigate the mitochondrial basis of avian
      adaptive thermogenesis in vitro. Skeletal muscle mitochondria isolated from
      penguins that had never been immersed in cold water showed no superoxide
      stimulated proton conductance, indicating no functional avian UCP. Skeletal
      muscle mitochondria from penguins that had been either experimentally immersed or
      naturally adapted to cold water did possess functional avian UCP, demonstrated by
      a superoxide-stimulated, GDP-inhibitable proton conductance across their inner
      membrane. This was associated with a markedly greater abundance of avian UCP
      mRNA. In the presence (but not the absence) of fatty acids, these mitochondria
      also showed a greater adenine nucleotide translocase-catalysed proton conductance
      than those from never-immersed penguins. This was due to an increase in the
      amount of adenine nucleotide translocase. Therefore, adaptive thermogenesis in
      juvenile king penguins is linked to two separate mechanisms of uncoupling of
      oxidative phosphorylation in skeletal muscle mitochondria: increased proton
      transport activity of avian UCP (dependent on superoxide and inhibited by GDP)
      and increased proton transport activity of the adenine nucleotide translocase
      (dependent on fatty acids and inhibited by carboxyatractylate).

PMID- 15146051
TI  - Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function
      and blood pressure in mature male guinea pigs.
AB  - Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on
      days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally.
      Adult male offspring were catheterized at 145 days of age and subjected to tests
      of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated
      states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased
      hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and
      increased mean arterial pressure. There were no effects on gestation length,
      birth weight and postnatal growth. There were no overall differences in diurnal
      plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there
      were subtle differences during the subjective afternoon between control and mat
      dex offspring. A significant decrease in initial ACTH suppression was observed
      following dexamethasone injection in mat-dex offspring compared to control
      offspring. Molecular analysis revealed significantly increased MR mRNA expression
      in the limbic system and particularly in the dentate gyrus in mat-dex offspring.
      In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid
      receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In
      conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC)
      permanently programmes organ growth, blood pressure and HPA regulation in mature
      male offspring and these changes involve modification of corticosteroid receptor
      expression in the brain and pituitary; (2) the effects of prenatal sGC exposure
      on HPA function appear to change as a function of age, indicating the importance
      of investigating HPA and cardiovascular outcome at multiple time points
      throughout life.

PMID- 15146052
TI  - Mechanosensory S-neurons rather than AH-neurons appear to generate a rhythmic
      motor pattern in guinea-pig distal colon.
AB  - Simultaneous intracellular recordings were made from myenteric neurons and
      circular muscle (CM) cells in isolated, stretched segments of guinea-pig distal
      colon. We have shown previously that maintained stretch generates a repetitive
      and coordinated discharge of ascending excitatory and descending inhibitory
      neuronal reflex pathways in the distal colon. In the presence of nifedipine (1-2
      microm) to paralyse the muscle, simultaneous recordings were made from 25 pairs
      of AH (after-hyperpolarization)-neurons and CM cells separated by 100-500 microm.
      In all 25 AH-neurons, proximal process potentials (PPPs) were never recorded,
      even though at the same time, all recordings from neighbouring CM cells showed an
      ongoing discharge of inhibitory junction potentials (IJPs) anally, or excitatory
      junction potentials (EJPs) orally. In fact, 24 of 25 AH-neurons were totally
      silent, while in one AH-cell, some spontaneous fast excitatory postsynaptic
      potentials (FEPSPs) were recorded. All 10 electrically silent AH-cells that were
      injected with neurobiotin were found to be multipolar Dogiel type II neurons. In
      contrast, when recordings were made from myenteric S-neurons, two distinct
      electrical patterns of electrical activity were recorded. Recordings from 25 of
      48 S-neurons showed spontaneous FEPSPs, the majority of which (22 of 25) showed
      periods when discrete clusters of FEPSPs (mean duration 88 ms) could be
      temporally correlated with the onset of EJPs or anal IJPs in the CM. Nine S
      neurons were electrically quiescent. The second distinct electrical pattern in 14
      S-neurons consisted of bursts, or prolonged trains of action potentials, which
      could be reduced to proximal process potentials (PPPs) in six of these 14 neurons
      during membrane hyperpolarization. Unlike FEPSPs, PPPs were resistant to a low
      Ca(2+)-high Mg(2+) solution and did not change in amplitude during
      hyperpolarizing pulses. Mechanosensory S-neurons were found to be uniaxonal or
      pseudounipolar filamentous neurons, with morphologies consistent with
      interneurons. No slow EPSPs were ever recorded from AH- or S-type neurons when
      IJPs or EJPs occurred in the CM. In summary, we have identified a population of
      mechanosensory S-neurons in the myenteric plexus of the distal colon which appear
      to be largely stretch sensitive, rather than muscle-tension sensitive, since they
      generate ongoing trains of action potentials in the presence of nifedipine. No
      evidence was found to suggest that in paralysed preparations, the repetitive
      firing in ascending excitatory or descending inhibitory nerve pathways was
      initiated by myenteric AH-neurons, or slow synaptic transmission.

PMID- 15146053
TI  - Stratum-by-stratum projection of light response attributes by retinal bipolar
      cells of Ambystoma.
AB  - The visual system processes light images by projecting various representations of
      the visual world to segregated regions in the brain through parallel channels.
      Retinal bipolar cells constitute the first parallel channels that carry different
      light response attributes to different parts of the inner plexiform layer (IPL).
      Here we present a systematic study on detailed axonal morphology and light
      response characteristics of over 200 bipolar cells in dark-adapted salamander
      retinal slices by the whole-cell voltage clamp and Lucifer yellow fluorescence
      (with a confocal microscope) techniques. Four major groups of bipolar cells were
      identified according to the patterns of axon terminal ramification in the IPL:
      36% were narrowly monostratified (whose axon terminals ramified in one of the 10
      strata of the IPL), 27% were broadly monostratified, 19% were multistratified,
      and 18% bore pyramidally branching axons. By analysing the bipolar cells with
      narrowly monostratified axon terminals in each of the 10 strata of the IPL, we
      found that several key light response attributes are highly correlated with the
      strata in which the cells' axon terminals ramify. The 10 IPL strata appear to be
      the basic building blocks for attributes of light-evoked signal outputs in all
      bipolar cells, and several general stratum-by-stratum rules were identified by
      analysing the broadly monostratified, multistratified and pyramidally branching
      cells. These rules not only uncover mechanisms by which third-order retinal cells
      integrate and compute bipolar cell signals, but also shed considerable light on
      how bipolar cells in other vertebrates process visual information and how
      physiological signals may shape the morphology and projection of output synapses
      of visual neurones during development.

PMID- 15146054
TI  - Adenosine decreases both presynaptic calcium currents and neurotransmitter
      release at the mouse neuromuscular junction.
AB  - A controversy currently exists as to the mechanism of action by which adenosine,
      an endogenous mediator of neurotransmitter depression, reduces the evoked release
      of the neurotransmitter acetylcholine (ACh) at the skeletal neuromuscular
      junction. Specifically, it is uncertain whether adenosine inhibits ACh release
      from mammalian motor nerve endings by reducing Ca(2+) calcium entry through
      voltage-gated calcium channels or, as is the case at amphibian motor nerve
      endings, by an effect downstream of Ca(2+) entry. In an attempt to address this
      controversy, the effects of adenosine on membrane ionic currents and
      neurotransmitter release were studied at neuromuscular junctions in adult mouse
      phrenic nerve hemidiaphragm preparations. In wild-type mice, adenosine (500
      microm-1 mm) reduced prejunctional Ca(2+) currents simultaneously with a
      reduction in evoked ACh release. In Rab3A knockout mice, which have been shown to
      have an increased sensitivity to adenosine, the simultaneous reduction in Ca(2+)
      currents and ACh secretion occurred at significantly lower adenosine
      concentrations (< or = 50 microM). Measurements of nerve terminal Na(+) and K(+)
      currents made simultaneously with evoked ACh release demonstrated that the
      decreases in Ca(2+) currents were not attributable to changes in cation entry
      through voltage-gated Na(+) or K(+) channels. Furthermore, no effects of
      adenosine on residual ionic currents were observed when P/Q-type calcium channels
      were blocked by Cd(2+) or omega-agatoxin-IVA. The results demonstrate that
      inhibition of evoked neurotransmitter secretion by adenosine is associated with a
      reduction in Ca(2+) calcium entry through voltage-gated P/Q Ca(2+) channels at
      the mouse neuromuscular junction. Whilst it may be that adenosine inhibits ACh
      release by different mechanisms at amphibia and mammalian neuromuscular
      junctions, it is also possible that the secretory apparatus is more intimately
      coupled to the Ca(2+) channels in the mouse such that an effect on the secretory
      machinery is reflected as changes in Ca(2+) currents.

PMID- 15146055
TI  - Transmembrane peptides as inhibitors of ErbB receptor signaling.
AB  - Receptor tyrosine kinases have a single transmembrane (TM) segment that is
      usually assumed to play a passive role in ligand-induced dimerization and
      activation of the receptor. However, mutations within some of these receptors,
      and recent studies with the epidermal growth factor (EGF) and ErbB2 receptors
      have indicated that interactions between TM domains do contribute to
      stabilization of ligand-independent and/or ligand-induced receptor dimerization
      and activation. One consequence of the importance of these interactions is that
      short hydrophobic peptides corresponding to these domains should act as specific
      inhibitors. To test this hypothesis, we constructed expression vectors encoding
      short fusion peptides encompassing native or mutated TM domains of the EGF,
      ErbB2, and insulin receptors. In human cell lines overexpressing the wild-type
      EGF receptor or ErbB2, we observed that the peptides are expressed at the cell
      surface and that they inhibit specifically the autophosphorylation and signaling
      pathway of their cognate receptor. Identical results were obtained with peptides
      chemically synthesized. Mechanism of action involves inhibition of dimerization
      of the receptors as shown by the lack of effects of mutant nondimerizing
      sequences, completed by density centrifugation and covalent cross-linking
      experiments. Our findings stress the role of TM domain interactions in ErbB
      receptor function, and possibly for other single-spanning membrane proteins.

PMID- 15146056
TI  - Mitosis-specific anchoring of gamma tubulin complexes by pericentrin controls
      spindle organization and mitotic entry.
AB  - Microtubule nucleation is the best known function of centrosomes. Centrosomal
      microtubule nucleation is mediated primarily by gamma tubulin ring complexes
      (gamma TuRCs). However, little is known about the molecules that anchor these
      complexes to centrosomes. In this study, we show that the centrosomal coiled-coil
      protein pericentrin anchors gamma TuRCs at spindle poles through an interaction
      with gamma tubulin complex proteins 2 and 3 (GCP2/3). Pericentrin silencing by
      small interfering RNAs in somatic cells disrupted gamma tubulin localization and
      spindle organization in mitosis but had no effect on gamma tubulin localization
      or microtubule organization in interphase cells. Similarly, overexpression of the
      GCP2/3 binding domain of pericentrin disrupted the endogenous pericentrin-gamma
      TuRC interaction and perturbed astral microtubules and spindle bipolarity. When
      added to Xenopus mitotic extracts, this domain uncoupled gamma TuRCs from
      centrosomes, inhibited microtubule aster assembly, and induced rapid disassembly
      of preassembled asters. All phenotypes were significantly reduced in a
      pericentrin mutant with diminished GCP2/3 binding and were specific for mitotic
      centrosomal asters as we observed little effect on interphase asters or on asters
      assembled by the Ran-mediated centrosome-independent pathway. Additionally,
      pericentrin silencing or overexpression induced G2/antephase arrest followed by
      apoptosis in many but not all cell types. We conclude that pericentrin anchoring
      of gamma tubulin complexes at centrosomes in mitotic cells is required for proper
      spindle organization and that loss of this anchoring mechanism elicits a
      checkpoint response that prevents mitotic entry and triggers apoptotic cell
      death.

PMID- 15146057
TI  - The entire Nup107-160 complex, including three new members, is targeted as one
      entity to kinetochores in mitosis.
AB  - In eukaryotes, bidirectional transport of macromolecules between the cytoplasm
      and the nucleus occurs through elaborate supramolecular structures embedded in
      the nuclear envelope, the nuclear pore complexes (NPCs). NPCs are composed of
      multiple copies of approximately 30 different proteins termed nucleoporins, of
      which several can be biochemically isolated as subcomplexes. One such building
      block of the NPC, termed the Nup107-160 complex in vertebrates, was so far
      demonstrated to be composed of six different nucleoporins. Here, we identify
      three WD (Trp-Asp)-repeat nucleoporins as new members of this complex, two of
      which, Nup37 and Nup43, are specific to higher eukaryotes. The third new member
      Seh1 is more loosely associated with the Nup107-160 complex biochemically, but
      its depletion by RNA interference leads to phenotypes similar to knock down of
      other constituents of this complex. By combining green fluorescent protein-tagged
      nucleoporins and specific antibodies, we show that all the constituents of this
      complex, including Nup37, Nup43, Seh1, and Sec13, are targeted to kinetochores
      from prophase to anaphase of mitosis. Together, our results indicate that the
      entire Nup107-160 complex, which comprises nearly one-third of the so-far
      identified nucleoporins, specifically localizes to kinetochores in mitosis.

PMID- 15146058
TI  - Functional characterization of Dma1 and Dma2, the budding yeast homologues of
      Schizosaccharomyces pombe Dma1 and human Chfr.
AB  - Proper transmission of genetic information requires correct assembly and
      positioning of the mitotic spindle, responsible for driving each set of sister
      chromatids to the two daughter cells, followed by cytokinesis. In case of altered
      spindle orientation, the spindle position checkpoint inhibits Tem1-dependent
      activation of the mitotic exit network (MEN), thus delaying mitotic exit and
      cytokinesis until errors are corrected. We report a functional analysis of two
      previously uncharacterized budding yeast proteins, Dma1 and Dma2, 58% identical
      to each other and homologous to human Chfr and Schizosaccharomyces pombe Dma1,
      both of which have been previously implicated in mitotic checkpoints. We show
      that Dma1 and Dma2 are involved in proper spindle positioning, likely regulating
      septin ring deposition at the bud neck. DMA2 overexpression causes defects in
      septin ring disassembly at the end of mitosis and in cytokinesis. The latter
      defects can be rescued by either eliminating the spindle position checkpoint
      protein Bub2 or overproducing its target, Tem1, both leading to MEN
      hyperactivation. In addition, dma1Delta dma2Delta cells fail to activate the
      spindle position checkpoint in response to the lack of dynein, whereas ectopic
      expression of DMA2 prevents unscheduled mitotic exit of spindle checkpoint
      mutants treated with microtubule-depolymerizing drugs. Although their primary
      functions remain to be defined, our data suggest that Dma1 and Dma2 might be
      required to ensure timely MEN activation in telophase.

PMID- 15146060
TI  - Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a
      eukaryotic flagellum.
AB  - The eukaryotic flagellum is a large structure into which specific constituent
      proteins must be targeted, transported and assembled after their synthesis in the
      cytoplasm. Using Trypanosoma brucei and a proteomic approach, we have identified
      and characterized a novel set of adenylate kinase proteins that are localized to
      the flagellum. These proteins represent unique isoforms that are targeted to the
      flagellum by an N-terminal extension to the protein and are incorporated into an
      extraaxonemal structure (the paraflagellar rod). We show that the N-terminal
      extension is both necessary for isoform location in the flagellum and sufficient
      for targeting of a green fluorescent protein reporter protein to the flagellum.
      Moreover, these N-terminal extension sequences are conserved in evolution and we
      find that they allow the identification of novel adenylate kinases in the genomes
      of humans and worms. Given the existence of specific isoforms of certain central
      metabolic enzymes, and targeting sequences for these isoforms, we suggest that
      these isoforms form part of a complex, "solid-phase" metabolic capability that is
      built into the eukaryotic flagellum.

PMID- 15146059
TI  - Characterization of a nonclathrin endocytic pathway: membrane cargo and lipid
      requirements.
AB  - Clathrin-independent endocytosis internalizes plasma membrane proteins that lack
      cytoplasmic sequences recognized by clathrin adaptor proteins. There is evidence
      for different clathrin-independent pathways but whether they share common
      features has not been systematically tested. Here, we examined whether CD59, an
      endogenous glycosylphosphatidyl inositol-anchored protein (GPI-AP), and major
      histocompatibility protein class I (MHCI), an endogenous, integral membrane
      protein, entered cells through a common mechanism and followed a similar
      itinerary. At early times of internalization, CD59 and MHCI were found in the
      same Arf6-associated endosomes before joining clathrin cargo proteins such as
      transferrin in common sorting endosomes. CD59 and MHCI, but not transferrin, also
      were observed in the Arf6-associated tubular recycling membranes. Endocytosis of
      CD59 and MHCI required free membrane cholesterol because it was inhibited by
      filipin binding to the cell surface. Expression of active Arf6 stimulated
      endocytosis of GPI-APs and MHCI to the same extent and led to their accumulation
      in Arf6 endosomes that labeled intensely with filipin. This blocked delivery of
      GPI-APs and MHCI to early sorting endosomes and to lysosomes for degradation.
      Endocytosis of transferrin was not affected by any of these treatments. These
      observations suggest common mechanisms for endocytosis without clathrin.

PMID- 15146061
TI  - Rho kinase regulates the intracellular micromechanical response of adherent cells
      to rho activation.
AB  - Local sol-gel transitions of the cytoskeleton modulate cell shape changes, which
      are required for essential cellular functions, including motility and adhesion.
      In vitro studies using purified cytoskeletal proteins have suggested molecular
      mechanisms of regulation of cytoskeleton mechanics; however, the mechanical
      behavior of living cells and the signaling pathways by which it is regulated
      remains largely unknown. To address this issue, we used a nanoscale sensing
      method, intracellular microrheology, to examine the mechanical response of the
      cell to activation of the small GTPase Rho. We observe that the cytoplasmic
      stiffness and viscosity of serum-starved Swiss 3T3 cells transiently and locally
      enhances upon treatment with lysophosphatidic acid, and this mechanical behavior
      follows a trend similar to Rho activity. Furthermore, the time-dependent
      activation of Rho decreases the degree of microheterogeneity of the cytoplasm.
      Our results reveal fundamental differences between intracellular elasticity and
      cellular tension and suggest a critical role for Rho kinase in the regulation of
      intracellular mechanics.

PMID- 15146062
TI  - Cell cycle-dependent regulation of a human DNA helicase that localizes in DNA
      damage foci.
AB  - Mutational studies of human DNA helicase B (HDHB) have suggested that its
      activity is critical for the G1/S transition of the cell cycle, but the nature of
      its role remains unknown. In this study, we show that during G1, ectopically
      expressed HDHB localizes in nuclear foci induced by DNA damaging agents and that
      this focal pattern requires active HDHB. During S and G2/M, HDHB localizes
      primarily in the cytoplasm. A carboxy-terminal domain from HDHB confers cell
      cycle-dependent localization, but not the focal pattern, to a reporter protein. A
      cluster of potential cyclin-dependent kinase phosphorylation sites in this domain
      was modified at the G1/S transition and maintained through G2/M of the cell cycle
      in vivo, coincident with nuclear export of HDHB. Serine 967 of HDHB was the major
      site phosphorylated in vivo and in vitro by cyclin-dependent kinases. Mutational
      analysis demonstrated that phosphorylation of serine 967 is crucial in regulating
      the subcellular localization of ectopically expressed HDHB. We propose that the
      helicase of HDHB operates primarily during G1 to process endogenous DNA damage
      before the G1/S transition, and it is largely sequestered in the cytoplasm during
      S/G2.

PMID- 15146063
TI  - Spatial and temporal regulation of Condensins I and II in mitotic chromosome
      assembly in human cells.
AB  - Two different condensin complexes make distinct contributions to metaphase
      chromosome architecture in vertebrate cells. We show here that the spatial and
      temporal distributions of condensins I and II are differentially regulated during
      the cell cycle in HeLa cells. Condensin II is predominantly nuclear during
      interphase and contributes to early stages of chromosome assembly in prophase. In
      contrast, condensin I is sequestered in the cytoplasm from interphase through
      prophase and gains access to chromosomes only after the nuclear envelope breaks
      down in prometaphase. The two complexes alternate along the axis of metaphase
      chromatids, but they are arranged into a unique geometry at the
      centromere/kinetochore region, with condensin II enriched near the inner
      kinetochore plate. This region-specific distribution of condensins I and II is
      severely disrupted upon depletion of Aurora B, although their association with
      the chromosome arm is not. Depletion of condensin subunits causes defects in
      kinetochore structure and function, leading to aberrant chromosome alignment and
      segregation. Our results suggest that the two condensin complexes act
      sequentially to initiate the assembly of mitotic chromosomes and that their
      specialized distribution at the centromere/kinetochore region may play a crucial
      role in placing sister kinetochores into the back-to-back orientation.

PMID- 15146064
TI  - Disruption of astral microtubule contact with the cell cortex activates a Bub1,
      Bub3, and Mad3-dependent checkpoint in fission yeast.
AB  - In animal and yeast cells, the mitotic spindle is aligned perpendicularly to the
      axis of cell division. This ensures that sister chromatids are separated to
      opposite sides of the cytokinetic actomyosin ring. In fission yeast, spindle
      rotation is dependent upon the interaction of astral microtubules with the
      cortical actin cytoskeleton. In this article, we show that addition of
      Latrunculin A, which prevents spindle rotation, delays the separation of sister
      chromatids and anaphase promoting complex-mediated destruction of spindle
      associated Securin and Cyclin B. Moreover, we find that whereas sister
      kinetochore pairs normally congress to the spindle midzone before anaphase onset,
      this congression is disrupted when astral microtubule contact with the actin
      cytoskeleton is disturbed. By analyzing the timing of kinetochore separation, we
      find that this anaphase delay requires the Bub3, Mad3, and Bub1 but not the Mad1
      or Mad2 spindle assembly checkpoint proteins. In agreement with this, we find
      that Bub1 remains associated with kinetochores when spindles are mispositioned.
      These data indicate that, in fission yeast, astral microtubule contact with the
      medial cell cortex is monitored by a subset of spindle assembly checkpoint
      proteins. We propose that this checkpoint ensures spindles are properly oriented
      before anaphase takes place.

PMID- 15146066
TI  - Lessons from border cell migration in the Drosophila ovary: A role for myosin VI
      in dissemination of human ovarian cancer.
AB  - Dissemination of ovarian cancer is a major clinical challenge and is poorly
      understood at the molecular level due to a lack of suitable experimental models.
      During normal development of the Drosophila ovary, a dynamic process called
      border cell migration occurs that resembles the migratory behavior of human
      ovarian cancer cells. In this study, we found that myosin VI, a motor protein
      that regulates border cell migration, is abundantly expressed in high-grade
      ovarian carcinomas but not in normal ovary and ovarian cancers that behave
      indolently. Inhibiting myosin VI expression in high-grade ovarian carcinoma cells
      impeded cell spreading and migration in vitro. Optical imaging and
      histopathologic studies revealed that inhibiting myosin VI expression reduces
      tumor dissemination in nude mice. Therefore, using genetic analysis of border
      cell migration in Drosophila is a powerful approach to identify novel molecules
      that promote ovarian cancer dissemination and represent potential therapeutic
      targets.

PMID- 15146065
TI  - Cholera toxin toxicity does not require functional Arf6- and dynamin-dependent
      endocytic pathways.
AB  - Cholera toxin (CT) and related AB(5) toxins bind to glycolipids at the plasma
      membrane and are then transported in a retrograde manner, first to the Golgi and
      then to the endoplasmic reticulum (ER). In the ER, the catalytic subunit of CT is
      translocated into the cytosol, resulting in toxicity. Using fluorescence
      microscopy, we found that CT is internalized by multiple endocytic pathways.
      Inhibition of the clathrin-, caveolin-, or Arf6-dependent pathways by
      overexpression of appropriate dominant mutants had no effect on retrograde
      traffic of CT to the Golgi and ER, and it did not affect CT toxicity.
      Unexpectedly, when we blocked all three endocytic pathways at once, although
      fluorescent CT in the Golgi and ER became undetectable, CT-induced toxicity was
      largely unaffected. These results are consistent with the existence of an
      additional retrograde pathway used by CT to reach the ER.

PMID- 15146068
TI  - Identification of Ald6p as the target of a class of small-molecule suppressors of
      FK506 and their use in network dissection.
AB  - FK506 inhibits the Ca2+/calmodulin-dependent protein phosphatase calcineurin,
      which plays a critical role in yeast subjected to salt stress. A chemical genetic
      screen for small molecules that suppress growth inhibition by high NaCl plus
      FK506 identified a structurally related class of suppressors of FK506 (SFKs)
      named SFKs 2-4. To identify possible protein targets for these small molecules, a
      genome-wide screen of approximately 4,700 haploid yeast deletion strains was
      undertaken for strains showing resistance to high NaCl plus FK506. This screen
      yielded a number of genes not previously implicated in salt stress, including
      ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which
      encodes an NAD+ kinase. Transcriptional profiling of yeast treated with SFK2
      indicated that the SFKs target the Ald6p pathway. In addition, screening of the
      deletion strains for hypersensitivity to SFK2 yielded ZWF1, encoding glucose-6
      phosphate dehydrogenase, which has been shown to play an overlapping role with
      Ald6p in NADPH production. Furthermore, the SFKs inhibited the activity of Ald6p
      in vitro. Having established that the SFKs target Ald6p, they were used as tools
      to implicate systematically other gene products in the Ald6p pathway, including
      Utr1p, which may function by supplying Ald6p with its NADP+ cofactor.
      Furthermore, growth improvement by the SFKs on high NaCl plus FK506 was shown to
      require GPD1, which encodes an NADH-dependent glycerol-3-phosphate dehydrogenase
      that is important for the production of glycerol in response to osmotic stress.

PMID- 15146067
TI  - Protein-lipid interactions and phosphoinositide metabolism in membrane traffic:
      insights from vesicle recycling in nerve terminals.
AB  - Great progress has been made in the elucidation of the function of proteins in
      membrane traffic. Less is known about the regulatory role of lipids in membrane
      dynamics. Studies of nerve terminals, compartments highly specialized for the
      recycling of synaptic vesicles, have converged with studies from other systems to
      reveal mechanisms in protein-lipid interactions that affect membrane shape as
      well as the fusion and fission of vesicles. Phosphoinositides have emerged as
      major regulators of the binding of cytosolic proteins to the bilayer.
      Phosphorylation on different positions of the inositol ring generates different
      isomers that are heterogeneously distributed on cell membranes and that together
      with membrane proteins generate a "dual keys" code for the recruitment of
      cytosolic proteins. This code helps controlling vectoriality of membrane
      transport. Powerful methods for the detection of lipids are rapidly advancing
      this field, thus complementing the broad range of information about biological
      systems that can be obtained from genomic and proteomic approaches.

PMID- 15146069
TI  - Suppression of pathogen-inducible NO synthase (iNOS) activity in tomato increases
      susceptibility to Pseudomonas syringae.
AB  - Inducible NO synthase (iNOS) activity is induced upon pathogen inoculation in
      resistant, but not susceptible, tobacco and Arabidopsis plants. It was shown
      recently that a variant form of the Arabidopsis P protein (AtvarP) has iNOS
      activity. P protein is part of the glycine decarboxylase complex (GDC). It is
      unclear whether P protein also has iNOS activity and, if so, whether AtvarP, P,
      or both, play a role in plant defense. Here, we show that iNOS activity is
      induced in both resistant and susceptible tomato leaves upon inoculation with the
      Pseudomonas syringae pv. tomato strain DC3000. Virus-induced gene-silencing
      targeting LevarP, a putative tomato ortholog of AtvarP, led to complete
      suppression of DC3000-induced iNOS activation and an approximately 80% reduction
      in GDC activity; it also increased disease-symptom severity and DC3000 growth in
      both resistant and susceptible tomato. To determine whether enhanced
      susceptibility exhibited by LevarP-silenced, susceptible tomato was due to loss
      of (i) iNOS activity, (ii) GDC activity, or (iii) both, GDC activity was
      inhibited with or without concurrent suppression of iNOS. Treatment with
      methotrexate inhibited both iNOS and GDC activities and resulted in increased
      susceptibility, comparable with that observed in LevarP-silenced plants. When
      normal iNOS activity was maintained in the presence of methotrexate by the
      addition of tetrahydrobiopterin, there was no change in susceptibility, despite a
      dramatic reduction in GDC activity. Together, these results indicate that iNOS
      contributes to host defense response against DC3000.

PMID- 15146071
TI  - Reevaluation of the conclusion that IRES-activity reported within the 5' leader
      of the TIF4631 gene is due to promoter activity.
AB  - We previously reported that the 5' leader of the mRNA-encoding initiation factor
      eIF4G in Saccharomyces cerevisiae can function as a translational enhancer and as
      an internal ribosome entry site (IRES) when tested in cells. However, Verge and
      colleagues recently suggested that this sequence does not facilitate translation
      initiation, but inhibits translation in vitro and has promoter activity when
      tested in cells. We disagree with these conclusions and respond by showing that
      the data are most consistent with an internal initiation mechanism.

PMID- 15146070
TI  - Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana: a factor of
      potential importance for auxin-cytokinin-regulated development.
AB  - One of the most long-lived models in plant science is the belief that the long
      distance transport and ratio of two plant hormones, auxin and cytokinin, at the
      site of action control major developmental events such as apical dominance. We
      have used in vivo deuterium labeling and mass spectrometry to investigate the
      dynamics of homeostatic cross talk between the two plant hormones. Interestingly,
      auxin mediates a very rapid negative control of the cytokinin pool by mainly
      suppressing the biosynthesis via the isopentenyladenosine-5'-monophosphate
      independent pathway. In contrast, the effect of cytokinin overproduction on the
      entire auxin pool in the plant was slower, indicating that this most likely is
      mediated through altered development. In addition, we were able to confirm that
      the lateral root meristems are likely to be the main sites of
      isopentenyladenosine-5'-monophosphate-dependent cytokinin synthesis, and that the
      aerial tissue of the plant surprisingly also was a significant source of
      cytokinin biosynthesis. Our demonstration of shoot-localized synthesis, together
      with data demonstrating that auxin imposes a very rapid regulation of cytokinin
      biosynthesis, illustrates that the two hormones can interact also on the
      metabolic level in controlling plant development, and that the aerial part of the
      plant has the capacity to synthesize its own cytokinin independent of long-range
      transport from the root system.

PMID- 15146073
TI  - Sequence motifs that distinguish ATP(CTP):tRNA nucleotidyl transferases from
      eubacterial poly(A) polymerases.
AB  - ATP(CTP):tRNA nucleotidyl transferases, tRNA maturing enzymes found in all
      organisms, and eubacterial poly(A) polymerases, enzymes involved in mRNA
      degradation, are so similar that until now their biochemical functions could not
      be distinguished by their amino acid sequence. BLAST searches and analysis with
      the program "Sequence Space" for the prediction of functional residues revealed
      sequence motifs which define these two protein families. One of the poly(A)
      polymerase defining motifs specifies a structure that we propose to function in
      binding the 3' terminus of the RNA substrate. Similar motifs are found in other
      homopolyribonucleotidyl transferases. Phylogenetic classification of nucleotidyl
      tranferases from sequenced genomes reveals that eubacterial poly(A) polymerases
      have evolved relatively recently and are found only in a small group of bacteria
      and surprisingly also in plants, where they may function in organelles.

PMID- 15146074
TI  - A novel partial modification at C2501 in Escherichia coli 23S ribosomal RNA.
AB  - Escherichia coli is the best-characterized organism with respect to
      posttranscriptional modifications of its ribosomal RNA (rRNA). It is presently
      believed that all the modified nucleotides have been identified, primarily on the
      basis of two detection methods; modification-induced inhibition of the enzyme
      reverse transcriptase or analysis by combined HPLC and electrospray ionization
      mass spectrometry. Comparison of data from these different approaches reveals a
      disagreement regarding modification of C2501 in E. coli 23S rRNA. A. Bakin and J.
      Ofengand previously reported the detection of a modification at this site based
      on a reverse transcriptase assay. J.A. McCloskey and coworkers could not confirm
      the existence of such a modification using an electrospray ionization mass
      spectrometry approach. C2501 is therefore generally considered unmodified. We
      have used a strategy involving isolation of a specific rRNA fragment from E. coli
      23S rRNA followed by Matrix Assisted Laser Desorption/Ionization mass
      spectrometry and tandem mass spectrometry to investigate this controversy. Our
      data reveal a novel 16-Da partial modification at C2501. We believe that the data
      reported here clarify the above discrepancy, because a minor partial modification
      detected in a reverse transcriptase assay would not necessarily be detected by
      the original mass spectrometry approach. The level of modification was
      furthermore monitored in different growth situations, and we found a significant
      positive regulation in stationary phase cells. C2501 is universally conserved and
      implicated in structure folds very close to the catalytic center of the ribosome.
      Moreover, several antibiotics bind to nucleotides in this region, which
      altogether make a modification at this site interesting.

PMID- 15146075
TI  - Complete cycles of bloodstream trypanosome RNA editing in vitro.
AB  - RNA editing in kinetoplastid protists is required for the maturation of
      mitochondrial pre-mRNAs and occurs by protein-catalyzed cycles of uridylate
      insertion and deletion. During the complex life cycle of Trypanosoma brucei this
      process is differentially regulated in the mammalian bloodstream and insect
      procyclic stages. Complementary guide RNAs (gRNAs) direct editing, but the
      abundance of these transcripts is not developmentally controlled. The
      establishment of in vitro systems that recreate efficient RNA editing in
      bloodstream T. brucei would be valuable for mechanistic studies of regulation.
      Here we describe a robust in vitro system that reconstitutes full cycles of both
      U insertion and U deletion in bloodstream trypanosomes, and the first direct
      comparisons of the in vitro systems for strains of mammalian and insect stages.

PMID- 15146076
TI  - Multiple functions for the invariant AGC triad of U6 snRNA.
AB  - The invariant AGC triad of U6 snRNA plays an essential, unknown role in splicing.
      The triad has been implicated in base-pairing with residues in U2, U4, and U6.
      Through a genetic analysis in S. cerevisiae, we found that most AGC mutants are
      suppressed both by restoring pairing with U2, supporting the significance of
      U2/U6 helix Ib, and by destabilizing U2 stem I, indicating that this stem
      regulates helix Ib formation. Intriguingly, one of the helix Ib base pairs is
      required specifically for exon ligation, raising the possibility that the
      entirety of helix Ib is required only for exon ligation. We also found that U4
      mutations that reduce complementarity in U4 stem I enhance U2-mediated
      suppression of an AGC mutant, suggesting that U4 stem I competes with the AGC
      containing U4/U6 stem I. Implicating an additional, essential function for the
      triad, three triad mutants are refractory to suppression--even by simultaneous
      restoration of pairing with U2, U4, and U6. An absolute requirement for a purine
      at the central position of the triad parallels an equivalent requirement in a
      catalytically important AGC triad in group II introns, consistent with a role for
      the AGC triad of U6 in catalysis.

PMID- 15146077
TI  - The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2
      dependent spliceosome.
AB  - U11 and U12 snRNPs bind U12-type pre-mRNAs as a preformed di-snRNP complex,
      simultaneously recognizing the 5' splice site and branchpoint sequence. Thus,
      within the U12-type prespliceosome, U11/U12 components form a molecular bridge
      connecting both ends of the intron. We have affinity purified human 18S U11/U12
      and 12S U11 snRNPs, and identified their protein components by using mass
      spectrometry. U11/U12 snRNPs lack all known U1 snRNP proteins but contain seven
      novel proteins (i.e., 65K, 59K, 48K, 35K, 31K, 25K, 20K) not found in the major
      spliceosome, four of which (59K, 48K, 35K, and 25K) are U11-associated. Thus,
      protein-protein and protein-RNA interactions contributing to 5' splice site
      recognition and/or intron bridging appear to differ significantly in the minor
      versus major prespliceosome. The majority of U11/U12 proteins are highly
      conserved in organisms known to contain U12-type introns. However, homologs of
      those associated with U11 were not detected in Drosophila melanogaster,
      consistent with the presence of a divergent U11 snRNP in flies. RNAi experiments
      revealed that several U11/U12 proteins are essential for cell viability,
      suggesting they play key roles in U12-type splicing. The presence of unique
      U11/U12 snRNP proteins in the U12-type spliceosome provides insight into
      potential evolutionary relationships between the major and minor spliceosome.

PMID- 15146078
TI  - Xenopus U3 snoRNA docks on pre-rRNA through a novel base-pairing interaction.
AB  - U3 small nucleolar RNA (snoRNA) is essential for rRNA processing to form 18S
      ribosomal RNA (rRNA). Previously, it has been shown that nucleolin is needed to
      load U3 snoRNA on pre-rRNA. However, as documented here, this is not sufficient.
      We present data that base-pairing between the U3 hinges and the external
      transcribed spacer (ETS) is critical for functional alignment of U3 on its pre
      rRNA substrate. Additionally, the interaction between the U3 hinges and the ETS
      is proposed to serve as an anchor to hold U3 on the pre-rRNA substrate, while box
      A at the 5' end of U3 snoRNA swivels from ETS contacts to 18S rRNA contacts.
      Compensatory base changes revealed base-pairing between the 3' hinge of U3 snoRNA
      and region E1 of the ETS in Xenopus pre-rRNA; this novel interaction is required
      for 18S rRNA production. In contrast, base-pairing between the 5' hinge of U3
      snoRNA and region E2 of the ETS is auxiliary, unlike the case in yeast where it
      is required. Thus, higher and lower eukaryotes use different interactions for
      functional association of U3 with pre-rRNA. The U3 hinge sequence varies between
      species, but covariation in the ETS retains complementarity. This species
      specific U3-pre-rRNA interaction offers a potential target for a new class of
      antibiotics to prevent ribosome biogenesis in eukaryotic pathogens.

PMID- 15146079
TI  - The structure of a ribosomal protein S8/spc operon mRNA complex.
AB  - In bacteria, translation of all the ribosomal protein cistrons in the spc operon
      mRNA is repressed by the binding of the product of one of them, S8, to an
      internal sequence at the 5' end of the L5 cistron. The way in which the first two
      genes of the spc operon are regulated, retroregulation, is mechanistically
      distinct from translational repression by S8 of the genes from L5 onward. A 2.8 A
      resolution crystal structure has been obtained of Escherichia coli S8 bound to
      this site. Despite sequence differences, the structure of this complex is almost
      identical to that of the S8/helix 21 complex seen in the small ribosomal subunit,
      consistent with the hypothesis that autogenous regulation of ribosomal protein
      synthesis results from conformational similarities between mRNAs and rRNAs. S8
      binding must repress the translation of its own mRNA by inhibiting the formation
      of a ribosomal initiation complex at the start of the L5 cistron.

PMID- 15146081
TI  - Secondary structure models of the 3' untranslated regions of diverse R2 RNAs.
AB  - The RNA structure of the 3' untranslated region (UTR) of the R2 retrotransposable
      element is recognized by the R2-encoded reverse transcriptase in a reaction
      called target primed reverse transcription (TPRT). To provide insight into
      structure-function relationships important for TPRT, we have created alignments
      that reveal the secondary structure for 22 Drosophila and five silkmoth 3' UTR R2
      sequences. In addition, free energy minimization has been used to predict the
      secondary structure for the 3' UTR R2 RNA of Forficula auricularia. The predicted
      structures for Bombyx mori and F. auricularia are consistent with chemical
      modification data obtained with beta-ethoxy-alpha-ketobutyraldehyde (kethoxal),
      dimethyl sulfate, and 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p
      toluene sulfonate. The structures appear to have common helices that are likely
      important for function.

PMID- 15146080
TI  - Functions for S. cerevisiae Swd2p in 3' end formation of specific mRNAs and
      snoRNAs and global histone 3 lysine 4 methylation.
AB  - The Saccharomyces cerevisiae WD-40 repeat protein Swd2p associates with two
      functionally distinct multiprotein complexes: the cleavage and polyadenylation
      factor (CPF) that is involved in pre-mRNA and snoRNA 3' end formation and the
      SET1 complex (SET1C) that methylates histone 3 lysine 4. Based on bioinformatic
      analysis we predict a seven-bladed beta-propeller structure for Swd2p proteins.
      Northern, transcriptional run-on and in vitro 3' end cleavage analyses suggest
      that temperature sensitive swd2 strains were defective in 3' end formation of
      specific mRNAs and snoRNAs. Protein-protein interaction studies support a role
      for Swd2p in the assembly of 3' end formation complexes. Furthermore, histone 3
      lysine 4 di-and tri-methylation were adversely affected and telomeres were
      shortened in swd2 mutants. Underaccumulation of the Set1p methyltransferase
      accounts for the observed loss of SET1C activity and suggests a requirement for
      Swd2p for the stability or assembly of this complex. We also provide evidence
      that the roles of Swd2p as component of CPF and SET1C are functionally
      independent. Taken together, our results establish a dual requirement for Swd2p
      in 3' end formation and histone tail modification.

PMID- 15146082
TI  - A general method for rapid and nondenaturing purification of RNAs.
AB  - A key bottleneck in RNA structural studies is preparing milligram quantities of
      RNA, and current techniques have changed little in over a decade. To address
      this, we have developed an affinity tag-based purification method of RNA
      oligonucleotides. The tag is attached to the 3'-end of almost any desired RNA
      sequence, allowing for the rapid and specific removal of the RNA of interest
      directly from in vitro transcription reactions using an affinity column to which
      a specific RNA-binding protein has been attached. Following a wash, the RNA of
      interest is eluted by the addition of imidazole to the column, activating a
      mutant HdeltaV ribozyme incorporated into the tag. The affinity column can then
      be rapidly regenerated using conditions that release the protein-RNA tag
      interaction without denaturing the protein. To demonstrate that this method
      rapidly generates high-quality RNA, we have transcribed, purified, and generated
      diffraction-quality crystals of a mutant form of the Tetrahymena thermophila P4
      P6 domain in a 48-h time period.

PMID- 15146083
TI  - Detection and quantitation of RNA base modifications.
AB  - Using a new combination of previously published techniques, we developed a method
      for quantitating modified nucleotides in RNAs. First, an RNA is cleaved with
      RNase H at the 5' side of a nucleotide of interest. Next, 32P is substituted for
      the phosphate at the 5' end of this nucleotide. Finally, after nuclease P1
      digestion, the released radiolabeled nucleotide is analyzed by thin layer
      chromatography and quantitated by PhosphorImager. Using this method, we showed
      that the analysis of a pseudouridine at a specific site within an in vitro
      synthesized U2 RNA is indeed quantitative. We also applied this technique to
      cellular U2 RNA isolated from mouse liver, and showed that position U34 is
      approximately 90% pseudouridylated. This method, combined with previously
      described reverse transcription-based methods, constitutes a powerful tool for
      detecting and quantifying modified nucleotides in RNAs. With minor modifications,
      this method can serve as an effective assay to study RNA modifying enzymes.

PMID- 15146084
TI  - Epidemiology of erectile dysfunction.
AB  - Following the landmark Massachusetts Male Aging Study (MMAS) that provided the
      first relatively unbiased study of the epidemiology of erectile dysfunction (ED),
      a number of additional studies were carried out in the U.S. and around the world.
      The studies vary in quality because they used different definitions of ED,
      different assessment instruments, different and sometimes biased sources of
      populations, inadequate response rates to questionnaires and interviews, cultural
      disparities in willingness to discuss sexual issues, and differing
      interpretations of the results. Nevertheless, the studies demonstrated similar
      levels of ED by age and an exponential rise with age. They also generally
      confirmed the conditions that correlated with ED in the MMAS, namely, diabetes,
      hypertension, coronary artery disease, prostate cancer therapy, and depression.
      These were exacerbated by cigarette smoking.

PMID- 15146085
TI  - Physiology and biochemistry of erections.
AB  - The physiology of erection has received intense clinical and basic research
      scrutiny over the past two decades. This massive effort has led to a much clearer
      understanding of the macroscopic aspects of erection as well as identification of
      the prominent features of the etiology of erectile dysfunction (ED). However, it
      is clear that the devil is in the details of the erectile process. Therefore, to
      truly understand the precise mechanistic basis for erection and ED, much more
      still must be learned about how the biochemical cascades in the corporal smooth
      muscle cells are integrated to produce a normal erection, or how they are altered
      to result in ED. The ultimate goal of these basic research and clinical efforts
      will be to provide a rational scientific basis for mechanism-based, patient
      specific therapies for ED. This article reviews fundamental aspects of the
      physiology of erection and summarizes the most recent information available
      concerning the putative biochemical correlates of these physiologic events.

PMID- 15146086
TI  - Effect of androgens on penile tissue.
AB  - There are two ways to establish that androgens play a major role in the function
      and integrity of erectile tissue: (1) discussing a number of physiology and
      molecular biology studies that have been published from experiments in animals
      and (2) reporting the effect of androgens on penile tissue, or in many cases the
      lack of androgen, in man. A variety of animal models, and also human studies,
      have shown the existence of androgen receptors in the corpora cavernosa. The
      penile erectile response in the laboratory rat is androgen dependent, and the
      active androgen appears to be dihydrotestosterone. There are several articles
      that describe the androgenic regulation of nitric oxide synthase (the enzyme
      responsible for production of nitric oxide), the primary agent controlling the
      erectile cycle. There have been few reports showing a direct end organ dependency
      of androgen for erectile function in the human corpora cavernosa, although there
      is plenty of evidence demonstrating that low or absent androgens affect a man's
      ability to have an erection in a sexual situation. Thus, in man androgen
      dependency for cavernous tissue smooth muscle function is still debatable.
      Extrapolating animal dependency of androgens for molecular activity in the penile
      tissue remains the most reasonable suggestion for androgen dependency of the
      cavernous tissue in man.

PMID- 15146087
TI  - Evaluation of the patient with erectile dysfunction: history, questionnaires, and
      physical examination.
AB  - Historically the province of urologists and sex therapists, erectile dysfunction
      (ED) is now managed predominantly by primary care practitioners. In recognition
      of this trend, simplified assessment and treatment models have been proposed.
      These new treatment models strongly emphasize the need for sexual inquiry in all
      middle-age and older men but deemphasize the value of intensive medical or
      psychologic assessment in most cases. New management guidelines emphasize the
      need for a brief sexual and medical history, physical examination, and standard
      laboratory tests to rule out diabetes, dyslipidemia, or hypogonadism.

PMID- 15146088
TI  - Laboratory evaluation of the patient with erectile dysfunction.
AB  - Erectile dysfunction (ED) as a clinical entity is a problem that more than 50% of
      men will face as they age, and it can adversely affect overall quality of life
      and impact sexual partners. Our understanding of the pathophysiology and the
      multiple risk factors that contribute to ED has led to successful treatments,
      both non- surgical and surgical, over the past two decades. Now, more
      nonurologists and primary care providers are seeing patients for their initial
      evaluation. It is imperative that they approach the workup and evaluation in a
      logical and efficient manner. After a thorough history and physical examination,
      followed by a relevant and systematic laboratory evaluation, most cases can be
      effectively identified and medical treatment can be initiated. However, patients
      who continue to have erectile difficulties or fail initial oral treatment are
      candidates for specialized evaluation of vascular, neurogenic, and hormonal
      dysfunction, which can lead to more specific treatment or possible surgical
      management.

PMID- 15146089
TI  - Causes of erectile dysfunction.
AB  - Erectile dysfunction (ED) arises as a result of a collision of circumstances
      among any of a number of factors (e.g., risk factors, causes, probable
      associations), each with its own primary power to affect the outcome.
      Furthermore, each of the components has its own timing as part of a complex
      effort of compensation and adjustment that often obscures the individual details.
      In the end, ED results from a failure of local tissues or systemic supply and
      control structures. The power of any individual "cause" to degrade erectile
      function is an important but as-yet unquantified property. The power of a small
      abnormality over a long or critical period (e.g., organogenesis), or many small
      contributions, or multiple risk factors will certainly be greater than the sum of
      the individual elements. Without a full quantitation of pathways and their
      potential influence, one can compare the importance of causative factors only in
      limited ways. Not surprisingly, it is the presence of a multiplicity of
      unidentified or poorly understood causative factors that accounts in large
      measure for the current inability to cure and prevent ED. There are two other
      important properties of a putatively causative factor for ED--reversibility and
      preventability--and these are strongly influenced by the time of onset and the
      duration of impact. Thus, a critical understanding that comes from recognizing
      the importance of the temporal associations of component factors is that the
      causes of ED in an individual may be guessed at but cannot be fully disclosed by
      an analysis of a "snapshot" of the disease taken at the time of diagnosis.

PMID- 15146091
TI  - Psychotherapy for erectile dysfunction: now more relevant than ever.
AB  - The introduction of sildenafil in 1998 dramatically altered the treatment
      landscape for erectile dysfunction (ED). Although physicians now have a simple,
      efficacious, and safe treatment for ED, psychosocial barriers interfere with
      patients making effective use of these interventions. The role of psychotherapy
      is clearer than ever before in optimizing therapeutic outcome. The four goals of
      psychotherapy for ED are to identify and work through the resistances to medical
      intervention that lead to premature discontinuation; to reduce or eliminate
      performance anxiety; to understand the context in which men make love; and to
      implement psychoeducation and modification of sexual scripts. This article
      discusses three factors that make psychotherapy effective as well as outcome
      studies evaluating psychotherapy. By providing patients with an integrated
      medical/psychologic treatment, clinicians are likely to increase significantly
      the effectiveness of their treatment interventions for ED.

PMID- 15146090
TI  - Assessment of cardiovascular risk in patients with erectile dysfunction: focus on
      the diabetic patient.
AB  - Erectile dysfunction (ED) is commonly associated with risk factors for
      cardiovascular disease, including diabetes. The prevalence of ED in diabetic
      patients is high--about 75% of diabetic men 60 yr of age or older had ED in one
      study. Endothelial dysfunction, accelerated atherosclerosis, and diabetic
      neuropathy likely contribute to ED in diabetics. As silent ischemia is common in
      the diabetic patient, and diabetes is now often thought of as a coronary heart
      disease risk equivalent, diabetic men seeking therapy for ED may be considered
      candidates for exercise stress testing. Phosphodiesterase 5 (PDE5) inhibitors
      improve erectile function in diabetic men with ED; however, efficacy rates may be
      somewhat lower than in nondiabetic men. Studies to date have suggested that PDE5
      inhibitors per se do not cause an increase in myocardial infarction rates in men
      being treated for ED.

PMID- 15146092
TI  - Therapy of ED: PDE-5 Inhibitors.
AB  - The development of phosphodiesterase inhibitors, which are selective for the type
      5 isoenzyme, has revolutionized the initial evaluation and treatment of men with
      erectile dysfunction. These agents can be taken orally and are effective in 60
      70% of patients with erectile dysfunction, and they have low incidences of side
      effects when taken as recommended. The major contraindications are concomitant
      use with nitrates or the alpha-blockers terazosin and doxazosin. The major
      difference in the three approved inhibitors is that tadalafil has a considerably
      longer serum half-life, which provides a longer window of opportunity and
      potentially side effects.

PMID- 15146093
TI  - Androgen replacement in men with hypogonadism and erectile dysfunction.
AB  - The prevalence of hypogonadism and erectile dysfunction (ED) increases with age.
      Hypogonadism also is frequently associated with decreased libido and ED.
      Testosterone replacement therapy for hypogonadal ED is effective in restoring
      sexual desire and erectile function, especially in younger and healthy men. It
      appears to be less effective in older men with comorbid diseases that may cause
      ED. Therapy should be individualized, considered carefully, and closely monitored
      because of potential risks, especially in older men. The FDA has approved several
      testosterone delivery systems. These include a buccal testosterone tablet, intra
      muscular injections, transdermal and subcutaneous forms. There also are several
      promising experimental androgens under investigation including non-steroidal
      selective androgen receptor modulators (SARMs).

PMID- 15146095
TI  - External devices for treatment of erectile dysfunction.
AB  - Treatment of erectile dysfunction may now be approached in a variety of ways. The
      hope is to provide a treatment that is reliable, safe, and effective as well as
      acceptable to the patient. Many men are not candidates for surgery and may fail
      or have contraindications to medical therapy. This article addresses the oldest
      available form of noninvasive device therapy for the restoration of erectile
      function.

PMID- 15146096
TI  - Surgical management of erectile dysfunction.
AB  - Since the introduction of sildenafil citrate, oral systemic therapy has become
      the first line of therapy for men with erectile dysfunction (ED). Men who are not
      candidates for or who fail treatment with an oral agent may choose second-line
      therapies such as intraurethral prostaglandins, penile injection therapy, sex
      therapy, or a vacuum erection device. These secondline therapies may be
      unpalatable or inadequate for some men, and these men constitute the candidates
      for surgical intervention for ED. This article reviews surgical management of
      vascular ED, surgical management of Peyronie's disease, and penile prosthesis
      implantation. At the current time, the appropriate candidate for penile
      revascularization is a young man with proven arterial insufficiency resulting
      from pelvic trauma. Results in other populations are disappointing. Peyronie's
      disease with curvature significant enough to interfere with intercourse may be
      managed with tunical lengthening or shortening procedures in potent men and with
      prosthetic implantation in men with ED. Modern three-piece penile prostheses are
      associated with excellent device reliability, high rates of patient satisfaction,
      and acceptably low complication rates.

PMID- 15146094
TI  - Intracavernous pharmacotherapy for erectile dysfunction.
AB  - With the advent of phosphodiesterase type-5 inhibition as oral therapy,
      intracavernous injection of vasoactive agents has been relegated to second-line
      therapy for most patients with erectile dysfunction. However, the future of this
      category of agents remains bright as an ever-expanding number and combination of
      agents in use and under investigation will likely make intracavernous injection
      more appealing as greater efficacy, tolerability, and more rapid onset is
      attained. In this article, functional anatomy and physiology of human penile
      erection is reviewed, as are current clinical vasoactive agents including
      prostaglandin E-1, papaverine, and phentolamine. Emerging therapies discussed
      include guanylate cyclase activators, potassium channel openers, nitric oxide
      donors, vasoactive intestinal polypeptide, calcitonin gene-related peptide,
      selective alpha-1 receptor antagonists, and gene therapy. Ongoing research
      continues to define new roles for this effective and safe technique, which has
      withstood the test of time, restoring erectile function among patients with
      diverse ED etiologies and a variety of co-morbidities.

PMID- 15146099
TI  - Bone and fat: old questions, new insights.
AB  - Until recently, adipose tissue was considered to serve only as a triglyceride
      reservoir and was relegated to a passive endocrine role. With the discovery of
      leptin and other adipokines, adipose tissue is now recognized as an active
      participant in systemic metabolism. This review focuses on the complex
      relationship existing between adipose tissue and bone metabolism and
      differentiation. It explores the paradigms that have shaped the past decade's
      research and what these findings forecast for the future. Particular attention is
      given to the multipotent adult stem cell populations that reside within bone and
      fat. These adult stem cells have critical importance to the emerging field of
      tissue engineering and regenerative medicine.

PMID- 15146097
TI  - Therapy of erectile dysfunction: potential future treatments.
AB  - Current research on the development of new medical treatments of erectile
      dysfunction (ED) fall essentially into two main types of approaches: (1) the
      traditional strategy based on compounds acting to induce an erection on demand,
      without modifying the underlying pathologic alterations that lead to ED; and (2)
      more novel agents not inducing an erectile response but aiming for a long-term
      correction of either the defect in cavernosal tissue integrity responsible for
      functional impairment, or the impairment per se of the cavernosal tissue
      function. In the first approach, new phosphodiesterase inhibitors (either more
      potent and specific than the clinically available ones or harboring nitric oxide
      releasing structures), soluble guanylate cyclase activators, Rho kinase
      inhibitors, as well as centrally active agents stimulating hypothalamic dopamine
      or melanocortin receptors, combinations of different types of drugs, and new
      facilitators of tissue uptake of active agents, are being investigated and some
      may soon be applied clinically. In the second approach, the first type of
      correction comprises regulators of endogenous cell number and integrity and
      extracellular matrix turnover (inhibitors of apoptosis and fibrosis, neurotrophic
      and angiogenic factors), testosterone, and tissue and cell explants (nerve and
      smooth muscle grafting, adult pluripotent cells), whereas the second includes in
      vivo gene therapy with different genes and vectors, and ex vivo gene therapy,
      combining gene transfer with stem cell implants. This second approach requires
      extensive laboratory research prior to clinical translation but may provide a
      means to cure ED. The current status and future directions of these strategies
      are discussed.

PMID- 15146098
TI  - The role of TNF-alpha in insulin resistance.
AB  - Insulin resistance is an important component of the metabolic syndrome associated
      with obesity. Early-stage insulin-resistance and related mild glucose intolerance
      may be compensated by increased insulin secretion. When combined with impaired
      insulin secretion, insulin resistance plays an important role in type 2 diabetes
      (1). Insulin-resistance is also associated with a variety of pathological
      conditions, including trauma, infection, and cancer. Obesity and type 2 diabetes
      are the most common metabolic diseases in Western societies, together affecting
      as much as half of the adult population (2). The prevalence of these conditions
      is not only high, but continues to increase. We have only recently come to
      appreciate the role of fat, especially visceral fat, as an endocrine organ.
      Visceral fat is the source of a number of substances which might play a role in
      the development of insulin resistance. Among the latter are tumor necrosis factor
      alpha (TNF-alpha), adiponectin, IL-6, resistin and free fatty acids. This review
      will discuss the regulation of insulin responses by TNF-alpha and evidence
      supporting the hypothesis that over expression of TNF-alpha plays a role in the
      pathophysiology of insulin resistance.

PMID- 15146100
TI  - Basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating
      hormone charge isoform distribution and in vitro biological-to-immunological
      ratio in male puberty.
AB  - Follicle-stimulating hormone is synthesized and secreted as a mixture of
      heterogeneous isoforms that differ from each other in carbohydrate structure,
      biological potency, and plasma half-life. The relative abundance of the FSH
      isoforms will depend on the endocrine status of the donor at the time of sample
      collection. In the present study, we attempted to define the impact of the
      changing endocrine milieu characteristic of male puberty on the charge
      heterogeneity and plasma half-life of the serum FSH isoforms released under
      endogenous and exogenous GnRH drives, and examined whether such a varying hormone
      milieu modifies the capability of the circulating hormone to trigger
      intracellular signal transduction at the human FSH receptor level. Forty healthy
      male subjects at Tanner stages (Ts) 1 to 5 were sampled at 10 min intervals for
      10 h. Serum from successive samples collected across 2-4 h intervals containing
      FSH released under basal, low-dose (10 microg), and high-dose (90 microg)
      exogenous GnRH-stimulated conditions was subjected to preparative
      chromatofocusing and tested for bioactivity employing a homologous cell in vitro
      bioassay system. Deconvolution analysis was applied to estimate the apparent
      endogenous FSH plasma half-life in samples obtained after administration of low
      dose exogenous GnRH. Under all conditions studied, serum FSH charge isoforms were
      distributed along a pH range of 7.0 to less than 3.0. Comparisons across the
      different Tanner stages revealed a significant and selective increase in the
      ratio of FSH isoforms with elution pH values <4.50 relative to those with values
      >/=4.50 at Ts-2. At Ts-3, this ratio returned to that present at Ts-1, to decline
      thereafter during the ensuing pubertal stages. Serum bioactive FSH concentrations
      progressively increased (from 3.72 +/- 1.3 to 16.2 +/- 5.3 IU/L) throughout
      puberty, and in all conditions bioactive FSH concentrations exceeded those
      detected by a specific radioimmunoassay. The biological to immunological (B:I)
      FSH ratio at baseline was significantly (p < 0.05) lower at Ts-1 and Ts-2 (1.33
      +/- 0.30 and 1.62 +/- 0.34, respectively) than at more advanced stages of
      pubertal development (2.28 +/- 0.20, 2.96 +/- 0.38, and 2.77 +/- 0.63 at Ts-3-, 4
      , and -5, respectively) Similar differences were detected in samples containing
      FSH molecules released after low- and high-dose GnRH administration. The apparent
      endogenous FSH half-life of the deconvolved GnRH-induced FSH pulses was similar
      in the five study groups. These results demonstrate that the transition from
      infancy to sexual maturity in men is accompanied by qualitative changes in the
      circulating FSH isoform mixture. Although the changes in FSH glycosylation
      occurring throughout puberty are not of sufficient magnitude to alter the
      survival of the gonadotropin in circulation, they allow preferential secretion of
      bioactive FSH. The enrichment of the circulating mix of FSH isoforms with highly
      bioactive variants throughout spontaneous puberty may potentially favor the
      development of spermatogenesis and acquisition of reproductive competence.

PMID- 15146101
TI  - Stepwise posttranslational processing of progrowth hormone-releasing hormone
      (proGHRH) polypeptide by furin and PC1.
AB  - Through a posttranslational processing mechanism, pro-growth hormone releasing
      hormone (proGHRH) gives rise to an amidated GHRH molecule, which in turn
      stimulates the synthesis and release of growth hormone. We have previously
      proposed a model for the biochemical processing of proGHRH [Nillni et al. (1999),
      Endocrinology 140, 5817-5827]. We demonstrated that the proGHRH peptide (10.5
      kDa, 104 aa) is first processed to an 8.8 kDa intermediate form that is later
      cleaved to yield two products: the 5.2 kDa GHRH and the 3.6 kDa GHRH-RP. However,
      the proteolytic enzymes involved in this process are unknown. Therefore, in this
      study we determined which proconverting enzymes are involved in this process. We
      transfected different constructs in cell lines carrying different PC enzymes
      followed by analysis of the peptide products after metabolic labeling or Western
      blots. We found that in the absence of furin (LoVo cells) or CHO cells treated
      with BFA, only one moiety was observed, and that corresponds to the same
      electrophorectic mobility to the GHRH precursor. This finding strongly supports
      an initial role for furin in the processing of proGHRH. The results from
      transfections with preproGHRH alone or double or triple transfections with PC1
      and PC2 in AtT-20, GH3, and GH4C1 cells indicated that PC1 is the primary enzyme
      involved in the generation of GHRH peptide from the 8.8 kDa intermediate form. We
      found that AtT-20 cells (high PC1, very low PC2) were able to generate GHRH.
      However, GH3 cells (high PC2, but not PC1) were able to process the 8.8 kDa
      peptide to GHRH only after the cotransfection with the PC1 enzyme. Transfections
      with preproGHRH-GFP and preproGHRH-V5 provided similar results in all the cell
      lines analyzed. These data support the hypothesis that proGHRH is initially
      cleave by furin at preproGHRH29-30, followed by a second cleavage at preproGHRH74
      primarily by PC1 to generate GHRH and GHRH-RP peptides, respectively.

PMID- 15146102
TI  - Effects of raloxifene, one of the selective estrogen receptor modulators, on
      pituitary-ovary axis and prolactin in postmenopausal women.
AB  - To investigate the clinical effects of raloxifene, one of the selective estrogen
      receptor modulators (SERMs), on the pituitary-ovary axis and prolactin, a
      prospective, randomized, double-blinded study on 59 healthy postmenopausal women
      was performed. Forty-eight women received raloxifene 60 mg daily. The other 11
      received combined conjugated equine estrogen 0.625 mg and medroxyprogesterone
      acetate 5 mg daily (CCEP) as active controls. Serum follicle stimulating hormone
      (FSH), luteinizing hormone (LH), estradiol (E2), and pro-lactin were measured at
      baseline and 1 yr after treatment. The mean levels of FSH and LH were
      significantly decreased in the raloxifene group (FSH: -10.7%; p < 0.01, LH: 
      10.3%; p < 0.05) and CCEP group (FSH: -53.7%, p < 0.001; LH: -46.8%, p < 0.001).
      The prolactin level decreased in the raloxifene group but not in the CCEP group (
      17.0%; p < 0.001 vs +13.3%, p = no significance; NS). Consequently, long-term
      administration of raloxifene up to 1 yr decreases serum prolactin level
      significantly and may be a therapeutic alternative for postmenopausal
      osteoporotic women with hyperprolactinemia.

PMID- 15146103
TI  - Estrogen modulates developmentally regulated gene expression in the fetal baboon
      liver.
AB  - Although estrogen plays a central integrative role in regulating key aspects of
      placental and fetal endocrine development in the primate, our understanding of
      the regulation of maturation of the fetal liver is incomplete. In adults,
      estrogen modulates several aspects of hepatic function. Therefore, the current
      study determined whether fetal hepatic gene expression development was modulated
      by estrogen. mRNA differential display was used to identify genes whose
      expression was altered in fetal livers obtained on d 165 of gestation (term = d
      184) from baboons that were untreated or treated on d 60-164 with the aromatase
      inhibitor CGS 20267 (2 mg/d; sc), which suppressed estrogen levels in the fetus
      by >95% (p < 0.01). As confirmed by Northern blot, the mRNA levels (ratio to 18s
      RNA) of metallothionein I (MT-I), porphobilinogen deaminase (PBG-D), and
      cytochrome P450 2C8 (CYP 2C8) in the livers of estrogen-deprived fetuses were 5-,
      12-, and 3-fold higher (p < 0.05) than respective values of untreated fetuses.
      Moreover, mRNA levels of MT-I and PBG-D, expressed as a ratio to 18s RNA, were 3
      fold and 26-fold higher (p < 0.05) on d 60-100 of gestation than on d 165 and in
      the adult. In contrast, CYP 2C8 mRNA increased 10-fold between d 100 and 165 and
      was not further altered in adult liver. Immunohistochemistry confirmed expression
      of MT-I in hepatocytes. Erythropoietic cells, normally present in the fetal
      baboon liver on d 100 but not on d 165, were also detected on d 165 in animals
      treated with the aromatase inhibitor. Thus, upregulation of PBG-D mRNA in
      estrogen-deprived baboons may reflect prolongation of the erythropoietic role of
      the fetal liver. In summary, these results indicate that the normal developmental
      change in MT-I, PBG-D, and CYP 2C8 mRNA expression in baboon fetal liver with
      advancing gestation are dependent on increased secretion of estrogen into the
      fetus. We suggest, therefore, that estrogen regulates normal development of the
      primate fetal liver.

PMID- 15146105
TI  - Interactions between worm infections and malaria.
AB  - Helminths are the most prevalent parasitic infections and malaria is the
      deadliest parasitic disease. Helminths have been reported to be protective
      against the severe forms of malaria but they were also possibly linked to
      increased malaria-incidence and gametocyte carriage. Connecting the dots between
      observations suggests that statistical regularities throughout the evolution of
      worms and malaria parasites in the same hosts, may have led to the emergence of
      non-zero interactions as observed in iterated prisoners dilemma games. Thus by
      protecting the host, helminths protect themselves and their reproductive
      potential, but also favor the dissemination and reproduction of Plasmodium
      falciparum. The proximate causes of this evolutionarily stable strategy might be
      mediated by IgE and the CD23/NO pathway, the protective role of IL10 in helminth
      infected patients, and possibly the hematological consequences of worms. The
      chronic activation of the CD23/NO pathway might be instrumental in downregulating
      the expression of cytoadherence receptors thus reducing sequestration of
      parasitized red blood cells in the deep organs. Mild anemia in helminth-infected
      patients might favor gametocytogenesis and send attractive cues to the vector.
      This framework leads to numerous testable hypotheses and could explain certain
      singularities regarding the double edged role of IgE and NO. Among these
      hypotheses, there are 2 practical ones: the impact of helminths on malaria
      vaccine candidates, and the theoretical risk of increasing the severity of
      malaria after anthelmintics. The capacity for increased IgE responses could thus
      have been vital in our ancestor's wormy and malarious past. Allergies may be what
      remains of it in the modern world.

PMID- 15146104
TI  - The role of parasites in genetic susceptibility to allergy: IgE, helminthic
      infection and allergy, and the evolution of the human immune system.
AB  - There have been numerous studies in the mouse illustrating the dichotomy of T
      cell responses, with the common classification orchestrated around Th1 vs. Th2
      responses. This classification is now widely applied to human disease as well and
      the generic conclusion is that the Th1 responses are more likely to occur
      secondary to specific microbiologic insult but also inflammatory responses. In
      contrast, the Th2 response is the prevalent response in subjects with atopy and
      allergic disease but is also the mechanism for protection against helminthic
      infections. Unfortunately, the paradigm of Th1 vs. Th2 is not as clear in the
      human as it is in mouse models. Even so, the immunological mechanisms responsible
      for IgE production that are protective in helminthic infections, i.e.
      Schistosoma, are similar to those for the production of specific IgE against
      allergens. In fact, there also appear to be associations in the memory T cell
      subpopulation CD4+CD45RO+ and the elicitation of IgE against both parasites and
      allergens. In this review, we present the overall contemporary scheme on the role
      of parasites in genetic susceptibility to allergic IgE, helminthic infections
      with specific discussion of its implications for the evolution of the human
      immune system.

PMID- 15146106
TI  - Echinococcosis and allergy.
AB  - The larval stages of Echinococcus granulosus and E. multilocularis are involved
      in parasitic diseases in humans: cystic echinococcosis (CE) ("hydatid disease")
      and alveolar echinococcosis (AE), respectively. Both diseases and parasites have
      tight links with allergy because of the immunological characteristics that
      contribute to maintain the larvae in their human host as well as their potential
      in inducing clinical anaphylactic reactions in some patients. Clinical
      observations in patients and data obtained from mass screenings in various
      countries have identified both forms of echinococcosis as "polar diseases," i.e.,
      diseases where immunological background of the patients was related to the
      clinical presentation and course. In particular, abortive cases (i.e.,
      spontaneous cures) have been found in many subjects in endemic areas. On the
      other hand, immune suppression was associated with severe disease. AE especially
      might be considered as an opportunistic infection. Experimental and clinical
      studies have shown that Th1-related immune response was associated with
      protection and Th2-related response was associated with parasite growth. Genetic
      characteristics of the host are related to both occurrence and severity of AE and
      are associated with the extent of IL-10 secretion, which is a major feature of
      chronic progressing echinococcosis. Anaphylactic reactions, including urticaria,
      edema, respiratory symptoms, and anaphylactic shock due to spontaneous or
      provoked rupture of the parasitic cyst, are well known in CE. Anaphylactic
      reactions in AE are far less frequent, and have been observed in rare cases at
      time of metastatic dissemination of the parasitic lesions. Echinococcus-specific
      IgE is present in most of the patients and associated with severity. Specific
      histamine release by circulating basophils stimulated with E. granulosus antigens
      is present in all patients with CE and AE. Echinococcus allergens include (1) AgB
      12-kDa subunit, a protease inhibitor and a potent Th2 inducer; (2) Ag5, a serine
      protease; (3) EA 21, a specific cyclophilin, with a homology with other types of
      cyclophilins; (4) Eg EF-1 beta/delta an elongation factor, with a homology with
      Strongyloides stercoralis EF that shares the same IgE epitope. A clinical cross
      reaction with Thiomucase, a mucopolysaccharidase used in arthritis treatment, has
      recently been published. However, despite the potential risk of allergic
      reactions, the dogma "never puncture a hydatid cyst" is no longer valid.
      International experience of therapeutic technique of "puncture, aspiration,
      injection, re-aspiration" of hydatid cysts developed at the beginning of the
      1980s has proved to be successful in a variety of selected indications that have
      been reviewed by WHO recommendations. A better understanding of the immunological
      background of echinococcosis in humans has led to new therapeutic developments,
      such as immunomodulation using interferon alpha. Th2-driven immunological
      response and IL-10-related tolerance state are common characteristics of atopic
      allergy and echinococcosis. The example of echinococcosis stresses the ambiguous
      links that exist between parasitic and allergic diseases, and show the usefulness
      of comparing these diseases to better understand how immune deviation may lead to
      pathological events and to find new therapeutic and.or preventive agents.

PMID- 15146107
TI  - Allergies and parasitoses in sub-Saharan Africa.
AB  - There has been nearly an epidemic rise in allergic disease throughout the world.
      However, this significant increase in the prevalence of allergic diseases has not
      been reported on the African continent. There are many factors which have been
      offered to explain these differences, including nutrition, environmental factors
      and genetic contributions. In addition, these differences in allergic disease
      incidents have often been discussed in terms of the hygiene hypothesis. In this
      manuscript, we have focused our attention on specific interactions between
      parasitoses and allergic diseases and illustrate their interactions with
      socioeconomic, cultural, and sanitary realities. The data is particularly
      applicable to Senegal but can be extrapolated to other regions throughout the
      world and the results have implications for the induction of allergic disease in
      both western and Third World countries.

PMID- 15146109
TI  - Characterization of B lymphopoiesis in mouse bone marrow and spleen.
AB  - This chapter provides information on the application of flow cytometry for
      analysis of B-cell development, describing in detail the particular surface
      proteins that can serve as markers for recognizing distinct stages in this
      process. These cell fractions range from just prior to initial heavy chain
      rearrangement, the germline pro-B stage, through D-J rearranged pro-B and heavy
      chain expressing pre-B stages, to the maturing surface BCR positive B-cell
      stages. It also outlines assays for the characterization of these cells,
      including procedures for testing functional lineage restriction, determination of
      rearrangement status, analyses of gene expression at the ribonucleic acid (RNA)
      and protein level, and assessment of cell cycle state.

PMID- 15146110
TI  - Characterization of B-cell maturation in the peripheral immune system.
AB  - In the periphery different populations of B cells can be identified,
      corresponding to subsequent stages of B-cell development. Transitional 1 B cells
      are recent bone marrow emigrants traveling with the blood to the spleen. Here
      they further develop to transitional 2 and mature B cells. Marginal zone B cells
      are a sessile population only found in the spleen. The distinction of these cell
      types is only possible by three- and four-color flow cytometry, analyzing the
      relative expression of several developmentally regulated markers. We describe the
      method for the staining of the cells and the analysis of the collected data and
      show examples of the results obtained in normal and mutant mice.

PMID- 15146112
TI  - Analysis of B-cell life-span and homeostasis.
AB  - In the past, the life-span of B cells in rodents has been determined by a variety
      of methods, leading to conflicting results. Among the various techniques
      employed, labeling of dividing cells with the thymidine analog 5-bromo-2'
      deoxyuridine (BrdU) has turned out to be a versatile and reliable procedure.
      Labeling of the cells can be easily performed in vivo by feeding BrdU in the
      drinking water for extended periods of time or by an ip injection of BrdU for
      short-term labeling experiments. Using the protocol described, it is possible to
      combine flow cytometric detection of incorporated BrdU simultaneously with
      fluorescence staining of various cell surface markers.

PMID- 15146108
TI  - Toll-like receptors and immune response in allergic disease.
AB  - Allergic reactions are dominated by the preferential development of specific Th2
      responses against innocuous antigens in atopic individuals. This can reflect
      alterations in innate immune mechanisms. Toll-like receptors (TLRs) have evolved
      as key molecules in innate and adaptive immunity. Their activation by
      structurally distinct exogenous or endogenous ligands present at the cell
      microenvironment plays a critical role in antimicrobial defense. The global view
      is that TLR activation induces antigen-presenting cells to produce cytokines that
      favor Th1-type immune responses, suggesting that it might prevent the development
      of deleterious Th2 responses in allergy. On the basis of epidemiological studies
      and recent data, it has been established that TLRs play a role in the development
      of Th2 responses. However, more information is needed to fully understand the
      mechanism of TLR involvement and the implication of immune cells that express
      TLRs in the Th1/Th2 cytokine profiles. Several TLRs, such as TLR9, TLR7, and
      TLR8, can be considered as good target candidates. Some TLR ligands, such as CpG
      DNA, are effective adjuvants, strong inducers of both IL-5 and eosinophilia
      downregulation. They are also potential links to allergen epitopes that could
      provide new allergen-specific immunotherapy regimens for the treatment of
      allergic disorders.

PMID- 15146111
TI  - Identification of B-cell subsets: an exposition of 11-color (Hi-D) FACS methods.
AB  - In the last few years, the effectiveness of developmental and functional studies
      of individual subsets of cells has increased dramatically owing to the
      identification of additional subset markers and the extension of fluorescence
      activated cell sorter (FACS) capabilities to simultaneously measure the
      expression of more markers on individual cells. For example, introduction of a 6
      8 multiparameter FACS instrument resulted in significant advances in
      understanding B-cell development. In this chapter, we describe 11-color high
      dimensional (Hi-D) FACS staining and data analysis methods that provide greater
      clarity in identifying the B-cell subsets in bone marrow, spleen, and peritoneal
      cavity. Further, we show how a single Hi-D FACS antibody reagent combination is
      sufficient to unambiguously identify most of the currently defined B-cell
      developmental subsets in the bone marrow (Hardy fractions A-F) and the functional
      B-cell subsets (B-1a, B-1b, B-2, and marginal zone [MZ] B cells) in the
      periphery. Although we focus on murine B-cell subsets, the methods we discuss are
      relevant to FACS studies conducted with all types of cells and other FACS
      instruments. We introduce a new method for scaling axes for histograms or contour
      plots of FACS data. This method, which we refer to as Logicle visualization, is
      particularly useful in promoting correct interpretations of fluorescence
      compensated FACS data and visual confirmation of correct compensation values. In
      addition, it facilitates discrimination of valid subsets. Application of Logicle
      visualization tools in the Hi-D FACS studies discussed here creates a strong new
      base for in-depth analysis of B-cell development and function.

PMID- 15146113
TI  - Differentiation of B lymphocytes from hematopoietic stem cells.
AB  - Differentiation of B lymphocytes can be efficiently obtained when multipotent
      hematopoietic precursors are cocultured with stromal cell lines and soluble
      growth factors. Stromal cell lines provide yet-undefined signals required for the
      expansion of the precursor population and/or lineage commitment and soluble
      mediators. In consequence, the type of the exogenously added interleukins depends
      on the stromal support used in the assay. In contrast to S17 and OP9 stroma, the
      fibroblast line NIH3T3 does not support B-cell precursor expansion of CD19(+)
      fetal liver cells; neither does it induce B-lineage differentiation from
      embryonic multipotent progenitors, in the absence of added cytokines. Under these
      conditions c-kit ligand, interleukin-7 (IL-7), and Flt3 ligand (Flt3-L) are added
      to the cultures to ensure optimal B-cell differentiation. Another cytokine,
      stroma-derived lymphopoietin, can also be used instead of IL-7 in embryonic but
      not adult hematopoietic precursors.

PMID- 15146115
TI  - Conditional gene mutagenesis in B-lineage cells.
AB  - Since its first application in mice almost 10 yr ago, the Cre/loxP has become the
      system of choice to study gene function in vivo in a cell-type, stage-specific,
      and inducible manner. This chapter provides a set of updated protocols that will
      help the reader to construct a vector for conditional gene targeting, to in vitro
      manipulate embryonic stem (ES) cells and to rapidly identify successfully
      targeted ES colonies. It also provides an updated list of Cre strains currently
      used to assess gene function at defined stages of B-cell development and
      guidelines to generate single-copy, knock-in transgenes regulated in a Cre
      dependent manner.

PMID- 15146114
TI  - Analysis of lymphocyte development and function using the RAG-deficient
      blastocyst complementation system.
AB  - The RAG-deficient blastocyst complementation system (RBCS) represents a flexible
      and rapid method for the genetic analysis of lymphocyte function using a gene
      targeting approach. In chimeras derived from manipulated embryonic stem cells
      injected into VDJ recombination-incapable, RAG-deficient blastocysts, any
      lymphoid cells past the prolymphocytic stage will be embryonic stem cell-derived.
      This approach can therefore bypass pitfalls such as pleiotropy and embryonic
      lethality to allow the analysis of targeted gene mutations with respect to
      lymphocyte development and function in a genetically uniform cell population.
      Thanks to recent advances in targeting techniques and in mouse embryo
      manipulation, this remarkably efficient technique has become a highly feasible
      and useful addition to any immunology research program. In this review, we
      discuss the technical aspects of the procedure, as well as its advantages and
      drawbacks compared to alternative approaches, and our practical experience in
      establishing the system at the University of Rochester.

PMID- 15146116
TI  - Analysis of the germinal center reaction and in vivo long-lived plasma cells.
AB  - This chapter describes the analysis of long- and short-lived plasma cells on
      tissue sections. Mice are immunized with 4-hydroxy-3-nitrophenyl acetyl (NP)
      coupled to a T-cell-dependent carrier. Antigen-specific germinal center cells and
      extrafollicular plasma cells are identified by immunohistology on tissue
      sections. Plasma cells labeled with 5-bromo-2'-deoxyuridine (BrdU) pulses given
      during different phases of B-cell response are identified on spleen sections. To
      identify mutated cells originating from cells in germinal centers, antigen
      specific cells from spleen sections are isolated by microdissection. From these
      NP-specific recombined VDJ genes are amplified with family-specific primers by
      polymerase chain reaction (PCR) for deoxyribonucleic acid (DNA) sequencing. The
      methods described can be used to characterize origins and life-span of plasma
      cells in vivo.

PMID- 15146117
TI  - T-cell-dependent immune responses, germinal center development, and the analysis
      of V-gene sequences.
AB  - To determine whether an immune system is able to support T-cell-dependent
      affinity maturation one needs antigens that induce well-characterized immune
      responses. This chapter describes the response of the BALB/c mouse to hapten 2
      phenyl-4-ethoxymethylene-oxazolone (phOx) coupled to carrier protein chicken
      serum albumin (CSA). Immunization with this hapten carrier complex will induce
      the formation of germinal centers (GCs), the microenvironment where the process
      of affinity maturation takes place. Immunohistological techniques to label
      germinal centers and examine the development of the GC structure during the
      primary immune response are described. The process of affinity maturation can be
      studied by the analysis of the mutational pattern in the VkappaOx1 L-chain in
      single GC B cells directly dissected from frozen tissue sections. The VkappaOx1 L
      chain sequences are amplified by polymerase chain reaction (PCR), cloned, and
      sequenced. Methods are described to analyze V-gene sequences. Potential
      difficulties in the interpretation of the mutational pattern are discussed.

PMID- 15146118
TI  - Introduction of genes into primary murine splenic B cells using retrovirus
      vectors.
AB  - Primary murine splenic B cells can be cultured ex vivo and, following treatment
      with LPS, cytokines and/or CD40L proliferate, and undergo class switch
      recombination and terminal differentiation to become immunoglobulin-secreting
      plasmacytic cells. Methods are described here for introducing genes, encoding
      either normal or blocking forms of experimental proteins, into murine splenic B
      cells using retrovirus vectors. This makes it possible to study the effects of
      these proteins on late stages of B-cell development, including proliferation,
      class switch recombination, and plasmacytic differentiation.

PMID- 15146119
TI  - Immunoglobulin class switching: in vitro induction and analysis.
AB  - During an immune response, B lymphocytes can switch expression of immunoglobulin
      (Ig) class (isotype) from IgM to IgG, IgE, or IgA. This Ig class switch is based
      on a deoxyribonucleic acid (DNA) recombination event that results in an exchange
      of the gene segments coding for the constant region of the Ig heavy chain,
      although the Ig heavy chain variable region is retained. This process changes the
      effector functions of the corresponding antibody (Ab). Much of our current
      understanding of the molecular mechanisms of class switch recombination is based
      on the analysis of B cells induced to switch class of Ig in vitro. In vitro,
      murine and human naive B cells can be activated with bacterial
      lipopolysaccharides, anti-CD40 or CD40L, to undergo class switch recombination.
      Cytokine signals can direct class switch recombination to distinct classes; for
      example, interleukin-4 will target murine IgG1 and IgE, and human IgG4 and IgE.
      Here we describe the technologies for the isolation of B lymphocytes, their
      activation to class switching, and the analysis of Ig class switching.

PMID- 15146120
TI  - In vitro and in vivo assays of B-lymphocyte migration.
AB  - The development and functional activities of B lymphocytes critically depend on
      their migratory capacity. Both in vitro and in vivo assays can be used to assess
      the migratory ability of B cells. Filter-based transwell assays measure both
      spontaneous and chemoattractant-induced cell migration in vitro. Flow cytometric
      analysis of labeled cell subsets present in the input and migratory cells from
      transwell assays allows the assessment of the migratory capacity of specific cell
      types in a complex mixture of cells. A similar approach can be used to assess the
      migratory capacity of B cells transfected with a green fluorescent fusion
      protein. Despite the success of the transwell assay, attempts to image
      directionally migrating B cells have been limited. The assessment of the in vivo
      migratory capacity of genetically modified or pharmacologically treated B cells
      usually involves their adoptive transfer into recipient mice. The localization of
      transferred cells in lymphoid organs can be determined by immunohistochemistry
      and/or flow cytometric analysis of harvested tissues or cells. Because the proper
      localization of B cells in lymphoid organs is a multistep process, abnormal
      positioning can occur even in the absence of an intrinsic defect in cell
      migration.

PMID- 15146121
TI  - Analysis of antigen-specific B-cell memory directly ex vivo.
AB  - Helper T-cell-regulated B-cell memory develops in response to initial antigen
      priming as a cellular product of the germinal center (GC) reaction. On antigen
      recall, memory response precursors expand rapidly with exaggerated
      differentiation into plasma cells to produce the high-titer, high-affinity
      antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a
      high-resolution flow cytometric strategy to quantify the emergence and
      maintenance of antigen-specific memory B cells directly ex vivo. Extended cell
      surface phenotype establishes a level of cellular diversity not previously
      appreciated for the memory B-cell compartment. Using an "exclusion transfer"
      strategy, we ascertain the capacity of two distinct memory B-cell populations to
      transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence
      expressed messenger ribonucleic acid (mRNA) from single cells within the
      population to estimate the level of somatic hypermutation as the best molecular
      indicator of B-cell memory. In this chapter, we describe the methods used in each
      of these four sections that serve to provide high-resolution quantification of
      antigen-specific B-cell memory responses directly ex vivo.

PMID- 15146122
TI  - B-cell signal transduction: tyrosine phosphorylation, kinase activity, and
      calcium mobilization.
AB  - Signal transduction by the B-cell antigen receptor (BCR) regulates development,
      survival, and clonal expansion of B cells. The BCR complex comprises the membrane
      bound immunoglobulin molecule and the Ig-alpha/Ig-beta heterodimer, and was shown
      to form oligomeric structures. Antigen-mediated engagement of the BCR results in
      the tyrosine phosphorylation of multiple signaling proteins leading to calcium
      mobilization and the activation of downstream serine/threonine kinases as well as
      transcription factors. In pervanadate (PV)-treated B cells, comparable pathways
      are activated on expression of the BCR, indicating that the BCR can signal in an
      antigen-independent fashion as well. In this chapter, we describe the analysis of
      antigen-dependent and -independent tyrosine phosphorylation events as well as a
      method to study calcium mobilization from differentially stimulated B cells.
      Furthermore, we emphasize the use of phospho-specific antibodies (Abs) and low
      molecular-weight enzyme inhibitors in the process of mapping BCR-activated
      signaling pathways as well as determining activation states of signaling
      proteins.

PMID- 15146123
TI  - Isolation of lipid rafts from B lymphocytes.
AB  - Recent advances in cell biology have provided evidence that the plasma membrane
      is not a homogeneous lipid bilayer but rather contains within it sphingolipid-
      and cholesterol-rich membrane microdomains, termed lipid rafts, which serve as
      platforms for both receptor signaling and trafficking. In B lymphocytes lipid
      rafts appear to play a key role in the initiation of B-cell antigen receptor
      (BCR) signaling. Current methods to isolate lipid rafts rely on the relative
      detergent insolubility of lipid rafts as compared to the nonraft,
      glycerophospholipid bilayer. Here a method to isolate and characterize lipid
      rafts from B lymphocytes is described. Particular emphasis is given to the
      potential artifacts inherent in current procedures that rely on detergents to
      isolate lipid rafts and alternative technologies that may circumvent these.

PMID- 15146124
TI  - Molecular single-cell PCR analysis of rearranged immunoglobulin genes as a tool
      to determine the clonal composition of normal and malignant human B cells.
AB  - Owing to the nearly limitless diversity of immunoglobulin (Ig) variable-region
      gene rearrangements, such rearrangements represent ideal clonal markers for B
      lineage cells. This chapter describes an approach to isolate single cells from
      frozen tissue sections by microdissection using a hydraulic micromanipulator and
      the subsequent amplification of rearranged IgH and Igkappa genes from the cells
      in a seminested polymerase chain reaction (PCR) approach. The amplification of a
      priori unknown V-gene rearrangements is made possible by the usage of a
      collection of V-gene family-specific primers recognizing nearly all V-gene
      segments together with primer mixes for the J-gene segments. By sequence
      comparison of V-gene amplificates from distinct cells, the clonal relationship of
      the B-lineage cells can unequivocally be determined. As a large part of the V
      gene rearrangements is amplified, the approach is also useful to address
      additional issues, such as V-, D-, and J-gene usage and the presence and pattern
      of somatic mutations.

PMID- 15146125
TI  - Analysis of B-cell immune tolerance induction using transgenic mice.
AB  - Over the past 15 yr, the use of transgenic mice has led to significant advances
      in our understanding of immunological tolerance. In a normal repertoire the
      number of B cells with a single antigen receptor specificity is very small,
      making the study of their fate difficult. In contrast, animals that carry
      transgenes encoding rearranged immunoglobulin genes generate large numbers of B
      cells that, by the process of allelic exclusion, have an identical specificity.
      Exploitation of this effect has enabled the mechanisms involved in B-cell
      tolerance to be explored in some detail. In this review we use the hen egg
      lysozyme (HEL) model system to illustrate the generation and preparation of a
      transgene. In our example, we describe the generation of mice expressing HEL as a
      systemic, intracellular, membrane-bound self-antigen. The same principles and
      methods apply to immunoglobulin transgenes. We briefly discuss the techniques
      that could be used to explore mechanisms of tolerance to systemic intracellular
      antigens in these mice.

PMID- 15146126
TI  - Analysis of B-cell signaling using DT40 B-cell line.
AB  - A chicken DT40 B-cell line provides an excellent model system for the analysis of
      the function of genes related to B-cell antigen receptor (BCR) signaling.
      Crosslinking of BCR by micro-chain-specific antibody stimulates DT40 cells to
      undergo apoptosis. Activation of protein- tyrosine kinases (PTKs) and
      intracellular calcium signaling are essential for BCR-induced apoptosis. Because
      DT40 B cells are highly proliferative and readily integrate exogenous DNA by
      homologous recombination, gene targeting is conveniently employed to inactivate
      genes of interest. This chapter describes procedures for (1) generation of
      knockout DT40 cell line, (2) analysis of surface BCR expression, (3) detection of
      tyrosine-phosphorylated proteins, (4) detection of intracellular calcium
      mobilization, and (5) reconstitution of depleted gene by transfection.

PMID- 15146127
TI  - B-cell development and pre-B-1 cell plasticity in vitro.
AB  - B-lymphopoiesis in vivo is a very complex process that is influenced by
      cooperation between cells, cytokines, and other receptor-ligand interactions,
      which developmentally occur at different cellular stages. Various in vitro models
      have been very useful in unraveling this complex process of B-cell development.
      Here the protocols for how to grow and to study the differentiation of mouse pre
      B-1, as developed in our laboratory, are described. Moreover, the protocols of
      how to grow and to test the plasticity of Pax-5-deficient pre-B-1 cells are also
      outlined.

PMID- 15146128
TI  - Hope, attitudes, emotions, and expectations in healthcare providers of services
      to patients infected with HIV.
AB  - The results of this preliminary study of 94 healthcare providers show that they
      had high hope levels when working with patients infected with HIV. The providers
      named imparting hope during the counseling process as the most important
      intervention for increasing patients' treatment adherence. Although half of the
      respondents had uncertain expectations for the future of their patients, more
      than one third had hopeful expectations, with only a small minority having
      hopeless expectations. An overwhelming majority reported they did not have
      negative attitudes toward or uncomfortable feelings when working with patients
      who were infected with HIV, regardless of method of acquiring HIV, gender, or
      sexual orientation. Moreover, respondents seemed to have a balanced emotional
      state, with the majority reporting that they experienced more positive emotions
      than negative emotions when working with their patients over time. Implications
      for healthcare providers are discussed.

PMID- 15146129
TI  - Desire for a future pregnancy among women in Zimbabwe in relation to their self
      perceived risk of HIV infection, child mortality, and spontaneous abortion.
AB  - In a background of very high prevalence of human immunodeficiency virus (HIV)
      infection among women of childbearing age and the increasing demand for treatment
      to prevent mother-to-child transmission, we investigated the desire for a future
      pregnancy among women in Zimbabwe in relation to (1) self-perceived risk of HIV
      infection, (2) child mortality, and (3) spontaneous abortion. A random cross
      sectional sample of 2250 ever-married women aged 15-49 years was selected from
      6,828 households in rural and urban Zimbabwe. The sample was representative of
      the geographic distribution of women. One eligible subject was selected per
      household for a structured interview on factors associated with the desire for
      future pregnancy. Overall, 54% of the participants desired to get pregnant in
      future; 55% perceived themselves at high risk for HIV infection; 6% reported the
      death of at least one child less than the age of 5 years in the last 5 years; and
      12% reported at least one spontaneous abortion in the last 5 years. In multiple
      logistic regression analysis, reporting at least one child's death (OR = 1.77;
      95% CI 1.13-2.78) and at least one spontaneous abortion in the last 5 years (OR =
      1.81; 95% CI 1.08-3.04) were significantly associated with a higher desire to get
      pregnant; however, high self-perceived risk for HIV infection was not (OR = 0.85;
      95% CI 0.67-1.09). High self-perceived risk for infection with HIV was not
      associated with a lower desire for a future pregnancy among women in Zimbabwe in
      a high-prevalence area. In fact, our data suggest an increased desire for future
      pregnancy to replace childhood deaths or spontaneous abortions that may result
      from HIV infection. Voluntary HIV testing services are challenged with balancing
      counseling messages on the strong desire for children, the risk of mother-to
      child transmission, and poor fetal outcomes. Further research is needed to
      explore utilitarian-economic, social, and psychological values attributed to
      children by women and their partners. The involvement of men as partners in
      childbearing should be explored, as their desire for children may be the primary
      barrier to protective behavior change among women.

PMID- 15146130
TI  - Sexual risk profile of young men in Vancouver, British Columbia, who have sex
      with men and inject drugs.
AB  - We compared sexual risk behaviors of men who have sex with men and inject drugs
      (MSM/IDU) with those of other men who have sex with men (MSM). Of 910 MSM
      surveyed, 106 (12%) injected drugs in the previous year. MSM/IDU were younger
      than MSM and more likely to be HIV-seropositive, Aboriginal, economically
      disadvantaged, engaged in the trade of sex for money or drugs, and to report
      having female sexual partners. MSM/IDU reported more casual sexual partners and
      in multivariate analyses were twice as likely to report unprotected receptive
      anal intercourse with casual partners. These results, combined with those from
      previous analyses, suggest that the higher risk for HIV seroconversion among
      MSM/IDU in this cohort is attributable mainly to sexual rather than injection
      related exposures. Controlled assessments are needed to identify optimal sexual
      risk reduction strategies for MSM/IDU.

PMID- 15146131
TI  - Who and why? HIV-testing refusal during pregnancy: implication for pediatric HIV
      epidemic disparity.
AB  - To identify characteristics of pregnant women who refuse HIV testing and
      determine predictive factors and the reasons for refusal, we conducted face-to
      face interviews of pregnant women at prenatal clinics of public and private
      hospitals. We found 8% (n=65) of 826 pregnant women interviewed refused HIV
      testing. In bivariate analysis, foreign-born pregnant women residing in Los
      Angeles County were twice more likely to refuse HIV testing than U.S.-born
      pregnant women (odds ratio [OR] = 1.97, 95% confidence interval [CI] 1.11-3.49, p
      <.05). In a multivariate stepwise logistic regression model analysis, variables
      that were independent predictors of HIV testing refusal during pregnancy were
      being foreign-born (OR = 2.11, 95% CI 1.07-4.38), not receiving general
      information about HIV (OR = 7.48, 95% CI 1.86-30.01), and not receiving specific
      information about HIV and pregnancy (OR = 3.54, 95% CI 1.91-6.57). The most
      common reasons for testing refusal were being in a monogamous relationship for
      foreign-born women (41%) and already being tested for U.S.-born women (65%).

PMID- 15146132
TI  - Triangle of risk: urban American Indian women's sexual trauma, injection drug
      use, and HIV sexual risk behaviors.
AB  - A community-based mail survey of 155 urban American Indian women revealed 91%
      engaged in at least one lifetime HIV sexual or drug risk behavior, including 19%
      who had sex with an injection drug user and 7% who had traded sex. Sixty-eight
      percent of the respondents were sexually active in the last year, with more than
      half never using condoms. Six percent had ever injected nonprescription drugs;
      62% drank alcohol in the last year, with 28% reporting at least one occasion of
      consuming six or more drinks containing alcohol. Respondents reported high rates
      of lifetime physical (37%) and sexual (39%) assault, which was generally
      associated with lifetime but not more recent indicators of sexual and drug risk
      behavior. Injection drug use mediated the relationship between nonpartner sexual
      (but not physical) trauma and high-risk sexual behaviors. Findings underscore the
      need for the integrated assessment and treatment of abuse and substance use as
      well as more research on the risk behaviors of this understudied and underserved
      population.

PMID- 15146133
TI  - An assessment of HIV/AIDS risk in higher education students in Yerevan, Armenia.
AB  - Armenia's current sociopolitical and economic instability and the alarming HIV
      incidence rates in neighboring countries amplify its risk for a national
      epidemic. The goals of this study were to assess HIV/AIDS knowledge and risk
      behaviors among higher education students in Yerevan. Knowledge of HIV
      transmission through sexual intercourse was markedly higher than that on
      intravenous transmission and prevailing myths; however, HIV/AIDS knowledge was
      not related to risk behaviors. Tobacco and alcohol prevalence was relatively
      high. Students reported risky sexual behaviors, including inconsistent condom
      use, casual sex, and multiple partners. In addition to descriptive statistics
      delineating gender differences across the target behavioral domains, bivariate
      and multivariate statistical analyses were used to understand factors that
      contributed to increased risk, including early age of initiation and the
      relationship between substance use and risky sexual activity. The study results
      provide much-needed information for the development of school- and community
      based AIDS prevention programs in Armenia.

PMID- 15146134
TI  - Sexual risks among southern thai drug injectors.
AB  - Sexual risks for HIV transmission among injection drug users (IDUs) in Thailand
      are not well characterized. We surveyed 272 male IDUs about their background,
      sexual behaviors, and drug use at drug treatment clinics in southern Thailand.
      HIV seroprevalence was determined using enzyme immunoassay. Fifty-six percent of
      participants were sexually active, of whom 88% had sex mostly with a noninjecting
      regular partner (wife or steady girlfriend), reporting low rates (34%) of condom
      use. Among sexually active IDUs, 43% were HIV infected and only a few were aware
      of their HIV serostatus. Condom use was associated with history of HIV voluntary
      counseling and testing (VCT) and poor perceived health status in multivariate
      analysis. Unprotected sex with regular sexual partners is frequent among IDUs in
      southern Thailand, where most IDUs have not sought VCT services. AIDS prevention
      efforts should address access to VCT and condom promotion to sexually active
      couples to prevent sexual transmission of HIV.

PMID- 15146135
TI  - Writing about risk: use of daily diaries in understanding drug-user risk
      behaviors.
AB  - As part of a larger syringe access and HIV risk study, a subsample of 23 current
      injection drug users completed daily diaries, highlighting activities related to
      syringe acquisition, use, and discard. Diaries have been previously utilized in a
      variety of psychological, public health, and nutrition studies to assess risk as
      well as correlated behaviors. We piloted the diary methodology in three
      northeastern U.S. cities (Hartford and New Haven, CT, and Springfield, MA) to
      learn about correlates of HIV risk. We discovered that the method provided
      advantages over several other qualitative and ethnographic methods. Results
      indicate that daily diaries elucidated (1) patterns of injection drug use, (2)
      sporadic and high-risk events, (3) HIV and hepatitis risk related to the syringe
      life cycle, and (4) emotional correlates of drug use. Furthermore, we witnessed
      an unexpected intervention effect that the diary may have in the lives of drug
      users.

PMID- 15146136
TI  - Changes in the meaning of sexual risk behaviors among gay and bisexual male
      methamphetamine abusers before and after drug treatment.
AB  - Methamphetamine is widely used among gay and bisexual men in the West Coast of
      the United States, and is often used in combination with high-risk sexual
      activities. This study combined quantitative and qualitative research
      methodologies to examine sexual risk behaviors among gay and bisexual male
      methamphetamine abusers as they entered treatment and at 1-year follow-up
      evaluations. Findings from the quantitative follow-up data demonstrate that gay
      and bisexual men reduce sexual risk behaviors and sustain those reductions
      following substance abuse treatment, and qualitative data reveal the meaning of
      these behavior changes from the perspective of the participant. At 1-year
      evaluations, associated behaviors of methamphetamine use and sexual risk
      behaviors were lessened. Although condom use decreased slightly, participants
      reported fewer anonymous sexual partners, reductions in episodes of both
      receptive and insertive anal intercourse, and an increased sense of
      responsibility to disclose their HIV status. This study further demonstrates the
      value of coupling quantitative with qualitative data in understanding the
      meanings behind reductions in high-risk behaviors.

PMID- 15146137
TI  - Condom use as a dependent variable: a brief commentary about classification of
      inconsistent users.
AB  - Transformation of nonnormally distributed measures of condom use frequency can be
      problematic for researchers. Distributions are typically dichotomized. We used
      data collected from 483 university undergraduates in an anonymous, cross
      sectional survey to illustrate the value of a screening analysis before
      dichotomization. Inconsistent condom users were compared to consistent users with
      respect to 14 measures. Subsequently, inconsistent users were compared to those
      who never used condoms with regard to the same 14 measures. Findings suggest that
      a screening analysis is a potentially important aspect of analyzing distributions
      that assess frequency of condom use.

PMID- 15146139
TI  - "They don't come to listen": the experience of loneliness among older people in
      Kwahu, Ghana.
AB  - This article describes life conditions of elderly people in a rural community of
      Ghana. It deals with the paradoxical situation of elderly people who are still
      engaged in social activities and yet experience loneliness. It is argued that in
      spite of the respect given to them, elderly people are denied what they regard as
      the most valuable proof of respect and companionship: listening to their wisdom
      and advice. Their loss of that ultimate respect constitutes an experience of
      loneliness. The article is part of broader anthropological study on social and
      cultural meanings of growing old in a rural Ghanaian community.

PMID- 15146138
TI  - Tailoring interventions: understanding medical practice culture.
AB  - This article describes the results of a study that used intensive direct
      observations of eight medical practices to assess the factors affecting the
      barriers and facilitators to adult immunization for influenza and pneumonia. The
      study aimed to describe the culture of these practices by identifying key
      features that facilitate or deter the immunization process. The article presents
      profiles of six of the eight practices describing their cultural and
      organizational frameworks. Six features that are critical to an understanding of
      the cultures of these practices, particularly as they relate to receptivity to
      influenza immunization for diverse practices and patient populations, are
      highlighted. These include policies and procedures, funding source, physician
      philosophy, patient receptivity to provider recommendation, and physical
      environment and social environment. The article also discusses strategies for
      applying knowledge about the culture of each practice to introduce appropriate
      and feasible interventions aimed at increasing immunization rates.

PMID- 15146141
TI  - The inexorable rise of gender and the decline of sex: social change in academic
      titles, 1945-2001.
AB  - More than 30 million titles of "academic" articles, from the years 1945-2001,
      were surveyed for occurrences of the words sex and gender. At the beginning of
      this period, uses of gender were much rarer than uses of sex, and often used in
      the sense of a grammatical category. By the end of this period, uses of gender
      outnumbered uses of sex in the social sciences, arts, and humanities. Within the
      natural sciences, there was now more than 1 use of gender for every 2 uses of
      sex. The beginnings of this change in usage can be traced to Money's introduction
      of the concept of "gender role" in 1955 (J. Money, 1955). However, the major
      expansion in the use of gender followed its adoption by feminists to distinguish
      the social and cultural aspects of differences between men and women (gender)
      from biological differences (sex). Since then, the use of gender has tended to
      expand to encompass the biological, and a sex/gender distinction is now only
      fitfully observed.

PMID- 15146140
TI  - Predicting ethnic variation in adaptation to later life: styles of socioemotional
      functioning and constrained heterotypy.
AB  - It is an axiom of social gerontology that populations of older individuals become
      increasingly differentiated as they age. Adaptations to physical and social
      losses and the increased dependency that typically accompany greater age are
      likely to be similarly heterogeneous, with different individuals adjusting to the
      aging process in widely diverse ways. In this paper we consider how individuals
      with diverse emotional and regulatory profiles, different levels of religiosity,
      and varied patterns of social relatedness fare as they age. Specifically, we
      examine the relation between ethnicity and patterns of socioemotional adaptation
      in a large, ethnically diverse sample (N = 1118) of community-dwelling older
      adults. Cluster analysis was applied to 11 measures of socioemotional
      functioning. Ten qualitatively different profiles were extracted and then related
      to a measure of physical resiliency. Consistent with ethnographic and
      psychological theory, individuals from different ethnic backgrounds were unevenly
      distributed across the clusters. Resilient participants of African descent
      (African Americans, Jamaicans, Trinidadians, Barbadians) were more likely to
      manifest patterns of adaptation characterized by religious beliefs, while
      resilient US-born Whites and Immigrant Whites were more likely to be resilient as
      a result of non-religious social connectedness. Taken together, although these
      data underscore the diversity of adaptation to later life, we suggest that
      patterns of successful adaptation vary systematically across ethnic groups.
      Implications for the continued study of ethnicity in aging and directions for
      future research are given.

PMID- 15146142
TI  - Prenatal androgenization affects gender-related behavior but not gender identity
      in 5-12-year-old girls with congenital adrenal hyperplasia.
AB  - Gender assignment of children with intersexuality and related conditions has
      recently become highly controversial. On the basis of extensive animal research
      and a few human case reports, some authors have proposed the putative
      masculinization of the brain by prenatal hormones-indicated by the degree of
      genital masculinization-as the decisive criterion of gender assignment and have
      derived the recommendation that 46,XX newborns with congenital adrenal
      hyperplasia (CAH) and full genital masculinization should be assigned to the male
      gender. The purpose of this study was to test in CAH girls of middle childhood
      the assumption that prenatal androgens determine the development of gender
      identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30
      control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender
      play observation sessions, and a gender identity interview yielding scales of
      gender confusion/dysphoria. About half a year earlier, mothers had completed 2
      questionnaires concerning their children's gender-related behavior. The results
      showed that, as expected, CAH girls scored more masculine than control girls on
      all scales measuring gender-related behavior, with robust effect sizes. By
      contrast, neither conventionally significant differences nor trends were found on
      the 3 scales of the gender identity interview. We conclude that prenatal
      androgenization of 46,XX fetuses leads to marked masculinization of later gender
      related behavior, but the absence of any increased gender-identity
      confusion/dysphoria does not indicate a direct determination of gender identity
      by prenatal androgens and does not, therefore, support a male gender assignment
      at birth of the most markedly masculinized girls.

PMID- 15146143
TI  - A parent-report gender identity questionnaire for children.
AB  - This paper reports on the psychometric properties of a 16-item parent-report
      Gender Identity Questionnaire, originally developed by P. H. Elizabeth and R.
      Green (1984), to aid in the assessment of children with potential problems in
      their gender identity development. The questionnaire, which covered aspects of
      the core phenomenology of gender identity disorder (GID), was completed by
      parents of gender-referred children (N = 325) and controls (siblings, clinic
      referred, and nonreferred; N = 504), who ranged in age from 2.5-12 years (mean
      age, 7.6 years). Factor-analysis indicated that a one-factor solution, containing
      14 of the 16 items with factor loadings > or =.30, best fit the data, accounting
      for 43.7% of the variance. The gender-referred children had a significantly more
      deviant total score than did the controls, with a large effect size of 3.70. The
      GIQ total score had negligible age effects, indicating that the questionnaire has
      utility for assessing change over time. The gender-referred children who met the
      complete DSM criteria for GID had a significantly more deviant total score than
      did the children who were subthreshold for GID, although the latter group had a
      mean score that was closer to the threshold cases than to the controls. With a
      specificity rate set at 95% for the controls, the sensitivity rate for the
      probands was 86.8%. It is concluded that this parent-report gender identity
      questionnaire has excellent psychometric properties and can serve as a useful
      screening device for front-line clinicians, for whom more extensive, expensive,
      and time-consuming assessment procedures may be precluded.

PMID- 15146144
TI  - Gender nonconformity, childhood rejection, and adult attachment: a study of gay
      men.
AB  - Several childhood factors are reported to be associated with a homosexual
      orientation in men, including gender nonconformity and rejection by parents and
      peers. The purpose of this study was to explore the associations between these
      childhood factors and attachment anxiety (the tendency to experience anxiety
      regarding potential loss and rejection in close relationships) and attachment
      avoidance (the tendency to avoid versus seek out closeness in relationships) in
      gay and bisexual men. A community sample of 191 gay and bisexual men completed
      questionnaires and an attachment interview. Gender nonconformity was
      significantly associated with paternal, maternal, and peer rejection in
      childhood. In addition, paternal and peer rejection, but not maternal rejection,
      independently predicted attachment anxiety. Peer rejection and, to a lesser
      extent, paternal rejection mediated the association between gender nonconformity
      and attachment anxiety. Finally, peer rejection mediated the association between
      paternal rejection and attachment avoidance. Findings highlight the role of
      gender nonconformity in contributing to childhood rejection and the importance of
      peer relationships in the socialization of gay men.

PMID- 15146145
TI  - A twin study of sexual behavior in men.
AB  - The role of genetic and environmental influences on age of initiation of first
      sexual relations and engaging in sexual activity with multiple partners (10 or
      more partners in 1 year) was investigated in male twins (N = 6,744) from the
      Vietnam Era Twin Registry. Individual differences in both types of sexual
      behaviors were heritable, but only age of onset of sexual relations was
      significantly influenced by the environment shared by the twins. There was a
      moderate negative correlation between age of initiation of sexual relations and
      the multiple partners variable; initiating sexual relations earlier was
      associated with a higher probability of having multiple partners. The additive
      genetic influence on age of initiation also influenced the multiple partners
      variable. The substantial unique environmental influences on each variable were
      uncorrelated with each other. The data suggest that the observed association
      between age of initiation of sexual relations and having multiple partners is due
      to genetic influences common to both behaviors.

PMID- 15146147
TI  - Coming out experiences and psychological distress of Chinese homosexual men in
      Hong Kong.
AB  - This study adopted a cognitive-behavioral conceptual framework based on the
      Theory of Reasoned Action (TRA) in understanding coming out experiences and
      psychological distress of 187 Chinese gay men. Results showed that participants'
      coming out experiences were characterized by same-sex sexual fantasy at teenage
      years, followed by awareness of homosexual tendency, same-sex sexual contact, and
      then self-identification and disclosure of homosexual orientation in young
      adulthood. Regarding targets of disclosure, participants tended to disclose their
      sexual orientation to their gay friends first, followed by heterosexual friends,
      siblings, parents, and coworkers. This study also supported the extension of the
      TRA conceptual framework to Chinese societies. Results showed that a low level of
      psychological distress in Chinese gay men was linked to their coming out
      experiences, which were in turn related to TRA components of involvement and
      identification with gay communities and positive attitudes toward coming out.
      Limitations and implications were also discussed.

PMID- 15146146
TI  - The prevalence of bisexual and homosexual orientation and related health risks
      among adolescents in northern Thailand.
AB  - Homo- or bisexual (HB) adolescents may have greater and different health risks
      than the population of heterosexual adolescents. We assessed sexual orientation
      and health risk behaviors in 1,725 consenting 15- to 21-year-old vocational
      school students in northern Thailand. Data were collected using audio-computer
      assisted self-interviewing. Nine percent of males and 11.2% of females identified
      themselves as homo- or bisexual. HB males had an earlier mean age at sexual debut
      (14.7 years) and a higher mean number of lifetime sexual partners (7.9) than did
      heterosexual males (16.8 years and 5.8 partners, respectively). HB males (25.9%)
      and females (32.2%) were sexually coerced more often than were heterosexual males
      (4.6%) and females (19.6%). Drug use was reported significantly more frequently
      by HB females and significantly less frequently by HB males than by their
      heterosexual counterparts. HB males showed more signs of social isolation and
      depression than did heterosexual males. We conclude that HB adolescents in
      northern Thailand are at greater and different health risks than are their
      heterosexual counterparts. Differential health education messages for HB and
      heterosexual youth are warranted.

PMID- 15146148
TI  - Sexual practices and psychosocial correlates of current condom use among Chinese
      gay men in Hong Kong.
AB  - This study examined sexual practices, condom use, and psychosocial correlates of
      condom use in a convenience sample of 187 Chinese gay men in Hong Kong. Among
      those who were sexually active and answered the item on condom use (n = 164), 22%
      never used condoms, 39% were inconsistent condom users, and 39% used condoms
      every time they engaged in sexual activities in the past 6 months. Compared to
      inconsistent and noncondom users, consistent condom users had more positive
      feelings toward condom use, perceived greater vulnerability to STD/AIDS
      infections, showed greater self-acceptance and disclosure of their homosexual
      sexual orientation, were more involved with local gay communities, endorsed more
      favorable attitudes toward coming out, and had a lower level of perceived
      discrimination because of their homosexual sexual orientation. The two groups did
      not differ significantly on perceived partner reaction to condom use. Results of
      a logistic regression analysis showed that positive feelings toward condom use
      were the most salient correlate of consistent condom use.

PMID- 15146149
TI  - [Utility of contrast ultrasound imaging in focal liver lesions].

PMID- 15146150
TI  - Efficiency of hepatitis C virus screening strategies in general practice.
AB  - Hepatitis C viral infection (HCV) is a frequent and severe disease; screening
      strategies to-date remain insufficient. OBJECTIVE: To assess the efficiency of
      HCV screening of high-risk groups among patients consulting general
      practitioners. METHODS: A cost-effectiveness analysis was performed involving
      general medicine screening practices recorded during a survey of 127
      practitioners (10,041 patients) conducted in 1997. A reference strategy, defined
      as HCV screening for illicit drug users and transfused patients, and five
      extended strategies, where the screening population was broadened to include
      other risk groups as well, were considered. Average cost and marginal cost
      effectiveness ratios were determined for each extended strategy and compared with
      those observed for the reference strategy. The sensitivity of HCV screening to
      funding modalities, HCV seroprevalence and proportion of HCV high-risk groups
      among patients attending general practitioners was studied. RESULTS: The
      reference strategy was the most cost-effective method irrespective of the funding
      modality considered. Fixed practitioner payment was the least efficient funding
      modality. The average cost of one positive test was sensitive to variations of
      HCV seroprevalence in the high-risk group as well as the proportion of high-risk
      patients among the general practitioners' patients. CONCLUSION: Extension of
      hepatitis C screening to risk groups other than transfused patients and illicit
      drug users implies a substantial increase in healthcare costs as well as social
      consensus for such expenditures.

PMID- 15146151
TI  - [Staging systems in hepatocellular carcinoma].

PMID- 15146152
TI  - [Colorectal cancer in France: towards an improvement in therapy?].

PMID- 15146153
TI  - Changing practices for diagnosis and treatment of colorectal cancer in Calvados:
      1990-1999.
AB  - AIM: Two consensus conferences on management of colorectal cancer were conducted
      in France during the last ten Years: one regarding rectal cancers in 1994 and the
      other regarding colonic cancer in 1998. In the present study, we examined data
      collected in a local gastrointestinal cancer registry to investigate changes in
      management practices for colorectal cancer in a well-defined population seen
      between 1990 and 1999. METHODS: The study population consisted of 3 135 patients
      with colorectal cancer diagnosed in Calvados (an administrative district in
      northern France) from 1990 to 1999. Two periods were defined: P1=1990-1994 and
      P2=1995-1999. Multivariate logistic regression analysis was performed. RESULTS:
      No trends in stage of disease at diagnosis or rate of surgical resection were
      observed. For patients with cancer of the rectum, the rate of sphincter
      preservation increased significantly from 65.6% in P1 to 72.3% in P2, in men and
      in all patients under the age of 75 Years. For patients with cancer of the colon,
      the number of resection specimens with at least eight examined lymph nodes
      increased from 50.7% in P1 to 60.2% in P2. This trend predominated in university
      centers; for rectal cancer patients it was significant only in university
      centers. Prescription of adjuvant chemotherapy for stage III colonic cancer
      increased significantly: 41.4% in P1 and 52.5% in P2. No changes in prescription
      of adjuvant radiotherapy for rectal cancer were observed, irrespective of the
      stage at diagnosis. The proportion of patients managed in university centers
      decreased significantly over time from 30.5% in P1 to 27.6% in P2, with a
      corresponding increase in private clinics. CONCLUSION: Most of the trends
      observed during the study period began before the consensus conference guidelines
      were Issued. The consensus guidelines appear to have influenced management
      practices mainly in university centers, while the majority of patients are
      managed in non-university centers.

PMID- 15146154
TI  - Regional variations in management of rectal cancer in France.
AB  - BACKGROUND: Population-based registries provide excellent data for drawing an
      accurate picture of disease management practices. The purpose of this study was
      to determine whether diagnostic and therapeutic management practices for rectal
      cancer vary in different geographic regions of France. METHODS: Data Issued from
      nine cancer registries covering 11% of the French population. The files of 683
      patients with a rectal cancer diagnosed in 1995 were selected for analysis.
      RESULTS: Colonoscopy was performed in a mean of 91.6% of patients (range: 80.9%
      98.2%) (P=0.01). The practice of colonoscopy concomitantly with barium enema
      varied greatly, ranging from 1.9%-57.7% of patients (P<0.001). Pretherapeutic
      work-up practices were significantly different depending on the region with
      respect to: abdominal CT scans (13.4%-69.2%), thoracic CT scans (0.9%-13.2%) and
      tumor markers (46.8%-80.8%). There were no significant differences between
      geographic regions concerning rate of resection, use of colostomy, or tumor stage
      at diagnosis. Administration of adjuvant radiotherapy (mean, 46.8%; range: 21.6%
      70%; P<0.001) and adjuvant chemotherapy (mean, 24.1%; range: 10.3%-40.6%; P<0.05)
      varied significantly between regions. CONCLUSION: Diagnostic practices and
      administration of adjuvant treatments vary significantly between geographic
      regions in France. The recommendations of the French consensus guidelines are
      only partially adhered to. Practitioners and healthcare Authorities should be
      aware of these differences in order to provide more harmonious patient care.

PMID- 15146155
TI  - [Adenomas and adenocarcinomas of the ampulla of Vater: endoscopic therapy].

PMID- 15146156
TI  - [Inflammatory bowel disease and latent thrombocythemia: a novel cause of hepatic
      vein thrombosis?].
AB  - It has been suggested in previous studies, that inflammatory bowel disease can
      induce hepatic vein thrombosis. However, the main weakness of those studies was
      the lack of extensive screening of prothrombotic factors. We report an unusual
      association of severe inflammatory bowel disease, hepatic vein thrombosis and
      latent platelet proliferation disorder. Early treatment with heparin and
      cyclosporin administered intravenously induce a remission of intestinal disease
      and total disappearance of hepatic vein thrombosis. Extensive screening excluded
      the classical causes of hepatic vein thrombosis, inherited coagulation disorders
      and latent polycythemia by culture of erythroid progenitors without added
      erythropoietin. However, using recent bone marrow culture conditions, we observed
      spontaneous colony formation of megakaryocyte progenitors revealing latent
      thrombocythemia. In summary, progress in the diagnosis of haemostasis disorders,
      will probably confirm that one or more additional predisposing prothrombotic
      factors are needed to the development of hepatic vein thrombosis in inflammatory
      bowel disease. This hypothesis could explain the scarcity of this complication in
      inflammatory bowel disease. Moreover, this case-report suggests that
      administration of heparin at the onset of the thrombosis may induce a complete
      regression of the thrombus in hepatic veins.

PMID- 15146157
TI  - [Inflammatory colitis and chronic granulomatous disease, a steroid-dependent case
      report].
AB  - Chronic granulomatous disease may lead to inflammatory bowel disease with
      endoscopic and histological aspects similar to that observed in patients with
      Crohn's disease. Inflammatory symptoms are generally controlled by steroids, but
      resistant forms may need total colectomy. Therapeutic strategy in steroid
      dependent cases is not yet established. We report here the case of a patient with
      chronic granulomatous enteritis dependent on steroids at a daily dose of 20 mg.
      Azathioprine made it possible to withdraw steroid therapy without relapse over
      twenty Months and without infectious complication during the follow up.

PMID- 15146158
TI  - [Severe ischemic necrotizing cholangitis after intra-arterial iodine 131-labeled
      Lipiodol as therapy for hepatocellular carcinoma].

PMID- 15146159
TI  - [Probable hepatoxicity from epigallocatecol gallate used for phytotherapy].

PMID- 15146160
TI  - [Quinine-induced esophagitis].

PMID- 15146162
TI  - [Acute glimepiride-induced pancreatitis].

PMID- 15146161
TI  - [Results of treatment with COX-2 inhibitors and lanreotide in a patient with
      Menetrier's hypertrophic gastropathy].

PMID- 15146163
TI  - [Henoch-Schonlein purpura in an adult revealed by severe gastrointestinal
      involvement].

PMID- 15146164
TI  - [Piascledine-associated lymphocytic colitis].

PMID- 15146165
TI  - A great majority of GISTs with PDGFRA mutations represent gastric tumors of low
      or no malignant potential.
AB  - Gastrointestinal stromal tumors (GISTs) are KIT expressing spindle cell,
      epithelioid and rarely pleomorphic mesenchymal tumors. The majority of GISTs show
      gain-of-function KIT mutations. However, GISTs without KIT mutations and GISTs
      with weak or lack of immunohistochemical KIT expression have also been reported.
      Recently, gain-of-function mutations in exon 18 (activation loop) and exon 12
      (juxtamembrane domain) of the PDGFRA were identified in such tumors. The purpose
      of this study was to test the hypothesis that PDGFRA mutation may define a
      specific clinicopathologic subgroup of GISTs. A total of 447 KIT exon 11
      (juxtamembrane domain) mutation-negative GISTs were studied. DNA samples were
      obtained from formaldehyde-fixed paraffin-embedded tissues. Genomic sequences of
      PDGFRA exons 18 and 12 were evaluated for the mutations by PCR amplification and
      direct sequencing. PDGFRA exon 18 mutations were identified in 122 of 346 (35.3%)
      gastric GISTs and two of 75 (2.7%) intestinal GISTs. A great majority of these
      mutations represented simple T to A missense mutation at the codon 842 leading to
      substitution of the valine for aspartic acid (D842 V). However, in-frame
      deletions and deletions with point mutations clustering between codons 841-847
      were found in approximately 23% of all exon 18 mutations. Mutations in PDGFRA
      exon 12 were found only in 10 of 170 (5.8%) gastric and one of 54 (1.9%)
      intestinal GISTs negative for KIT exon 11 and PDGFRA exon 18 mutations. There
      were seven substitutions of aspartic acid for valine at codon 561 (V561D) and
      four in-frame deletions with point mutations clustering between codons 566 and
      571. The majority of GISTs with PDGFRA mutations had pure or predominant
      epithelioid morphology. Low mitotic activity, < or =5 mitoses/50HPF was detected
      in 81% of analyzed GISTs including larger, >5 cm tumors. Based on long-term
      follow-up (average 135 months), a majority (83.5%) of GISTs with PDGFRA mutations
      followed a benign course.

PMID- 15146166
TI  - Two different types of amyloid deposits--apolipoprotein A-IV and transthyretin-
      in a patient with systemic amyloidosis.
AB  - Certain forms of systemic amyloidosis have been associated with the pathologic
      deposition as fibrils of three different apolipoprotein-related proteins-
      apolipoprotein A-I, apolipoprotein A-II, and serum amyloid A. We have previously
      reported (Bergstrom et al, Biochem Biophys Res Commun 2001;285:903-908) that
      amyloid fibrils extracted from the heart of an elderly male with senile systemic
      amyloidosis contained, in addition to wild-type transthyretin-related molecules,
      an N-terminal fragment of yet a fourth apolipoprotein--apolipoprotein A-IV (apoA
      IV). We now provide the results of our studies that have established the complete
      amino-acid sequence of this approximately 70-residue component and, additionally,
      have shown this protein to be the product of an unmutated apoA-IV gene. Notably,
      the apoA-IV and transthyretin fibrils were not codeposited but, rather, had
      anatomically distinct patterns of distribution within the heart and other organs,
      as evidenced immunohistochemically, by variation in the ultra structural
      morphology and by differences in the intensity of Congo red birefringence. These
      findings provide the first conclusive evidence that two separate forms of
      amyloid, each derived from a wild-type amyloidogenic precursor protein, were
      present in a patient with systemic amyloidosis.

PMID- 15146168
TI  - Insulin resistance as a modifier of the relationship between dietary fat intake
      and weight gain.
AB  - OBJECTIVE: To investigate whether insulin resistance modifies the rate of weight
      gain associated with a high percent of energy intake from dietary fat. DESIGN:
      Longitudinal, observational population study. SUBJECTS: A total of 782
      nondiabetic Hispanic and non-Hispanic white free-living adult residents of the
      San Luis Valley in Colorado. MEASUREMENTS: Subjects were seen up to three times
      over a 14-y period. Weight, height, fasting insulin and glucose, diet by 24 h
      recall, and self-reported physical activity were collected at each visit.
      RESULTS: Percentage of energy intake from dietary fat was positively associated
      with weight gain over time (P=0.0103). High intake of dietary fat was more
      strongly related to weight gain in women than in men, and in those with lower
      total energy intake levels. The relationship between weight change and relative
      macronutrient intake also varied by baseline insulin sensitivity (P=0.0025).
      Weight gain over time in individuals with relative insulin resistance at
      baseline, as measured by QUICKI, was the greatest among those who consumed a
      higher percent of energy from fat. CONCLUSION: Percentage of total intake from
      dietary fat predicts weight change independent of total energy intake.
      Nondiabetic, insulin-resistant individuals are particularly susceptible to the
      weight gain associated with high levels of dietary fat intake. Further
      investigation into the relationship between insulin resistance, diet, and weight
      gain is warranted.

PMID- 15146167
TI  - Subcellular localization of the ABCG2 transporter in normal and malignant human
      gallbladder epithelium.
AB  - Epithelium of the gallbladder and biliary tract is exposed to high concentrations
      of potentially harmful exogenous and endogenous compounds excreted into primary
      bile. As the ATP-dependent efflux pump ABCG2 can prevent cellular accumulation of
      anticancer drugs, estrogen sulfate, xenobiotics, porphyrins, and sterols, its
      expression in the biliary tract might mediate protection by hindering their
      penetration. We therefore investigated the expression and subcellular
      distribution of ABCG2 in normal and malignant human gallbladder. After
      demonstrating ABCG2 expression in gallbladder epithelium by RT-PCR and Western
      blotting, we analyzed the subcellular localization of ABCG2 by indirect
      immunofluorescence in gallbladder adenocarcinoma specimens, and compared it to
      that in cholelithiasis, and normal gallbladder samples (n = 54). In control,
      cholelithiasis, and well-differentiated tumor samples (grade 1, T1-3), ABCG2 is
      present at the luminal membrane of epithelial cells, which was proven by
      colocalization of apical-bound TRITC-labeled lectin (wheat germ agglutinin). In
      poorly differentiated gallbladder adenocarcinomas, intracellular ABCG2, in
      addition to luminal ABCG2 immunoreactivity, was found in 13/21 carcinoma samples
      (grade 2 and 3, T2-4, P < 0.01). In 3/11 of grade 3 tumors, ABCG2 was present in
      the cytoplasmatic compartment only (P < 0.01). In proliferating bile ducts of
      cholangiocarcinomas, ABCG2 showed an analogous staining pattern with presence in
      cytosolic compartments. However, the apical marker enzyme neutral endopeptidase
      remained on the membrane in all samples. To study whether phosphatidylinositol 3
      kinase (PI3K) signaling might be necessary for ABCG2 membrane insertion, we
      treated freshly isolated human gallbladder epithelial cells with the PI3K
      inhibitor wortmannin. As assessed by indirect immunofluorescence, this maneuver
      redistributes ABCG2 to intracellular compartments. In conclusion, our data
      suggest a protective role for ABCG2 in well-differentiated gallbladder epithelial
      cells. Cytoplasmatic accumulation of ABCG2 in poorly differentiated carcinomas
      might coincide with malfunctioning of PI3K-signaling pathways during tumor
      progression.

PMID- 15146169
TI  - Chromosomal transformation in donor cells following allogeneic bone marrow
      transplantation.
AB  - We report here a monosomy 7 transformation of donor cells following matched
      unrelated, same sex, allogeneic bone marrow transplantation in a patient with
      severe congenital aplastic anemia. A PCR technique was employed to amplify
      microsatellite markers on chromosome 7 to confirm donor/recipient identity. We
      found that the transformation of monosomy 7 occurred in previously genetically
      normal donor cells. This study suggests that the microenvironment of the bone
      marrow of our patient with severe congenital aplastic anemia may have played a
      critical role in the development of monosomy 7 of normal donor cells and we
      conclude that chromosomal microsatellite marker analysis can be a valuable tool
      for precise donor/recipient differentiation in engraftment monitoring.

PMID- 15146170
TI  - Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cells by
      overexpression of AP-2alpha.
AB  - A previous report demonstrated that AP-2alpha favors the survival of ovarian
      cancer patients by clinical findings. However, the functional roles of AP-2alpha
      in human ovarian cancers have not been determined. To clarify the roles, we
      overexpressed AP-2alpha in SKOV3 human ovarian cancer cells, which originally
      possess little AP-2alpha. AP-2alpha overexpression changed cell morphology from
      spindle to epithelioid type and suppressed cell proliferation and invasion, which
      would be partially correlated with decreased phosphorylation levels of the erbB2,
      Akt and ERK pathways, increased E-cadherin and reduced pro-matrix
      metalloproteinase-2 levels. Moreover, nude mice intraperitoneally injected with
      AP-2alpha-overexpressing cells survived longer than those with neo-transfected
      cells. The present data represent the first direct evidence that AP-2alpha plays
      a tumor suppressive role in ovarian cancer.

PMID- 15146171
TI  - Backbone tracking by the SF2 helicase NPH-II.
AB  - Members of the DExH/D family of proteins, a subset of helicase superfamily 2
      (SF2), are involved in virtually all aspects of RNA metabolism. NPH-II, a
      prototypical member of this protein family, exhibits robust RNA helicase activity
      in vitro. Using a series of modified substrates to explore the unwinding
      mechanism of NPH-II, we observed that the helicase tracks exclusively on the
      loading strand, where it requires covalent continuity and specifically recognizes
      the ribose-phosphate backbone. NPH-II unwinding was unaffected by lesions and
      nicks on the top strand, which has a minimal role in substrate recognition. NPH
      II required physical continuity of phosphodiester linkages on the loading strand,
      although abasic regions were tolerated. These findings suggest that SF2 helicases
      are mechanistically distinct from other helicase families that can tolerate
      breaks in the loading strand and for which bases are the primary recognition
      determinant.

PMID- 15146172
TI  - Protein displacement by an assembly of helicase molecules aligned along single
      stranded DNA.
AB  - Helicases are molecular motors that unwind double-stranded DNA or RNA. In
      addition to unwinding nucleic acids, an important function of these enzymes seems
      to be the disruption of protein-nucleic acid interactions. Bacteriophage T4 Dda
      helicase can displace proteins bound to DNA, including streptavidin bound to
      biotinylated oligonucleotides. We investigated the mechanism of streptavidin
      displacement by varying the length of the oligonucleotide substrate. We found
      that a monomeric form of Dda catalyzed streptavidin displacement; however, the
      activity increased when multiple helicase molecules bound to the biotinylated
      oligonucleotide. The activity does not result from cooperative binding of Dda to
      the oligonucleotide. Rather, the increase in activity is a consequence of the
      directional bias in translocation of individual helicase monomers. Such a bias
      leads to protein-protein interactions when the lead monomer stalls owing to the
      presence of the streptavidin block.

PMID- 15146173
TI  - Crystal structure of a high-pressure/high-temperature phase of alumina by in situ
      X-ray diffraction.
AB  - Alumina (alpha-Al(2)O(3)) has been widely used as a pressure calibrant in static
      high-pressure experiments and as a window material in dynamic shock-wave
      experiments; it is also a model material in ceramic science. So understanding its
      high-pressure stability and physical properties is crucial for interpreting such
      experimental data, and for testing theoretical calculations. Here we report an in
      situ X-ray diffraction study of alumina (doped with Cr(3+)) up to 136 GPa and
      2,350 K. We observe a phase transformation that occurs above 96 GPa and at high
      temperatures. Rietveld full-profile refinements show that the high-pressure phase
      has the Rh(2)O(3) (II) (Pbcn) structure, consistent with theoretical predictions.
      This phase is structurally related to corundum, but the AlO(6) polyhedra are
      highly distorted, with the interatomic bond lengths ranging from 1.690 to 1.847 A
      at 113 GPa. Ruby luminescence spectra from Cr(3+) impurities within the quenched
      samples under ambient conditions show significant red shifts and broadening,
      consistent with the different local environments of chromium atoms in the high
      pressure structure inferred from diffraction. Our results suggest that the ruby
      pressure scale needs to be re-examined in the high-pressure phase, and that shock
      wave experiments using sapphire windows need to be re-evaluated.

PMID- 15146174
TI  - Tailoring ferromagnetic chalcopyrites.
AB  - If magnetic semiconductors are ever to find wide application in real spintronic
      devices, their magnetic and electronic properties will require tailoring in much
      the same way that bandgaps are engineered in conventional semiconductors.
      Unfortunately, no systematic understanding yet exists of how, or even whether,
      properties such as Curie temperatures and bandgaps are related in magnetic
      semiconductors. Here we explore theoretically these and other relationships
      within 64 members of a single materials class, the Mn-doped II-IV-V(2)
      chalcopyrites (where II, IV and V represent elements from groups II, IV and V,
      respectively); three of these compounds are already known experimentally to be
      ferromagnetic semiconductors. Our first-principles results reveal a variation of
      magnetic properties across different materials that cannot be explained by either
      of the two dominant models of ferromagnetism in semiconductors. On the basis of
      our results for structural, electronic and magnetic properties, we identify a
      small number of new stable chalcopyrites with excellent prospects for
      ferromagnetism.

PMID- 15146175
TI  - Hierarchically mesostructured doped CeO2 with potential for solar-cell use.
AB  - Many properties provided by supramolecular chemistry, nanotechnology and
      catalysis only appear in solids exhibiting large surface areas and regular
      porosity at the nanometre scale. In nanometre-sized particles, the ratio of the
      number of atoms in the surface to the number in the bulk is much larger than for
      micrometre-sized materials, and this can lead to novel properties. Here we report
      the preparation of a hierarchically structured mesoporous material from
      nanoparticles of CeO(2) of strictly uniform size. The synthesis involves self
      assembly of these 5-nm CeO(2) pre-treated nanoparticles in the presence of a
      structure directing agent (poly(alkylene oxide) block polymer). The walls of this
      hexagonal structured CeO(2) material are formed from the primary nanoparticles.
      The material possesses large pore volumes, high surface areas, and marked thermal
      stability, allowing it to be easily doped after synthesis whilst maintaining
      textural and mechanical integrity. It also exhibits a photovoltaic response,
      which is directly derived from the nanometric particle size-normal CeO(2) does
      not show this response. We have constructed operational organic-dye-free solar
      cells using nanometric ceria particles (in both mesostructured or amorphous
      forms) as the active component, and find efficiencies that depend on the
      illuminating power.

PMID- 15146176
TI  - Probing the dynamics of nanoparticle growth in a flame using synchrotron
      radiation.
AB  - Flame synthesis is one of the most versatile and promising technologies for large
      scale production of nanoscale materials. Pyrolysis has recently been shown to be
      a useful route for the production of single-walled nanotubes, quantum dots and a
      wide variety of nanostructured ceramic oxides for catalysis and electrochemical
      applications. An understanding of the mechanisms of nanostructural growth in
      flames has been hampered by a lack of direct observations of particle growth,
      owing to high temperatures (2,000 K), rapid kinetics (submillisecond scale),
      dilute growth conditions (10(-6) volume fraction) and optical emission of
      synthetic flames. Here we report the first successful in situ study of
      nanoparticle growth in a flame using synchrotron X-ray scattering. The results
      indicate that simple growth models, first derived for colloidal synthesis, can be
      used to facilitate our understanding of flame synthesis. Further, the results
      indicate the feasibility of studies of nanometre-scale aerosols of toxicological
      and environmental concern.

PMID- 15146177
TI  - Suramin inhibits death receptor-induced apoptosis in vitro and fulminant
      apoptotic liver damage in mice.
AB  - Suramin is a polysulfonated derivative of urea and has been widely used both to
      treat infections and as a chemotherapeutic drug. Suramin has been shown to
      inhibit growth factor signaling pathways; however, its effect on apoptosis is
      unknown. Here we show that suramin inhibits apoptosis induced through death
      receptors in hepatoma and lymphoma cells. It also inhibits the proapoptotic
      effect of chemotherapeutic drugs. The antiapoptotic mechanism is specific to cell
      type and is caused by reduced activation, but not altered composition, of the
      death-inducing signaling complex (DISC), and by inhibition of the initiator
      caspases 8, 9 and 10. Suramin also shows similar effects in in vivo models:
      apoptotic liver damage induced by CD95 stimulation and endotoxic shock mediated
      by tumor-necrosis factor (TNF) are inhibited in mice, but necrotic liver damage
      is not inhibited in a rat model of liver transplantation. Thus, the antiapoptotic
      property of suramin in the liver may be therapeutically exploited.

PMID- 15146178
TI  - Insulin regulation of hepatic gluconeogenesis through phosphorylation of CREB
      binding protein.
AB  - Hepatic gluconeogenesis is essential for maintenance of normal blood glucose
      concentrations and is regulated by opposing stimulatory (cyclic adenosine
      monophosphate, cAMP) and inhibitory (insulin) signaling pathways. The cAMP
      signaling pathway leads to phosphorylation of cAMP response element-binding
      (CREB) protein, resulting in recruitment of the coactivators CREB-binding protein
      (CBP) and p300 and subsequent activation of gluconeogenesis. Insulin signaling
      leads to phosphorylation of CBP at serine 436, a residue near its CREB
      interacting domain, but it is unknown whether this event modulates cAMP
      signaling. Here, we show in vitro and in 'knock-in' mice that a mutant CBP
      (S436A) is aberrantly recruited to CREB protein, resulting in inappropriate
      activation of gluconeogenesis in the fed state and glucose intolerance resulting
      from increased hepatic glucose production. We propose that insulin signaling may
      directly regulate many cAMP signaling pathways at the transcriptional level by
      controlling CBP recruitment.

PMID- 15146180
TI  - CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'.
AB  - Myelin basic protein-specific CD8(+) T cells can induce central nervous system
      autoimmunity; however, immune tolerance prevents these autoreactive cells from
      causing disease. To define the mechanisms that mediate tolerance, we developed
      two T cell receptor-transgenic mouse lines with different affinities for the H
      2K(k)-restricted myelin basic protein epitope consisting of amino acids 79-87
      (MBP(79-87)). We observed both thymic deletion and peripheral tolerance in the
      lower-affinity T cells. The higher-affinity T cells, however, showed no evidence
      of tolerance induction and were able to prevent tolerance of the lower-affinity T
      cells by removing H-2K(k)-MBP(79-87) complexes from antigen-presenting cells
      without proliferating. This form of immune regulation could limit responses of
      self-reactive T cells that escape other tolerance mechanisms.

PMID- 15146179
TI  - 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid
      hormone.
AB  - Thyroxine (T(4)) is the predominant form of thyroid hormone (TH).
      Hyperthyroidism, a condition associated with excess TH, is characterized by
      increases in metabolic rate, core body temperature and cardiac performance. In
      target tissues, T(4) is enzymatically deiodinated to 3,5,3'-triiodothyronine
      (T(3)), a high-affinity ligand for the nuclear TH receptors TR alpha and TR beta,
      whose activation controls normal vertebrate development and physiology. T(3)
      modulated transcription of target genes via activation of TR alpha and TR beta is
      a slow process, the effects of which manifest over hours and days. Although
      rapidly occurring effects of TH have been documented, the molecules that mediate
      these non-genomic effects remain obscure. Here we report the discovery of 3
      iodothyronamine (T(1)AM), a naturally occurring derivative of TH that in vitro is
      a potent agonist of the G protein-coupled trace amine receptor TAR1.
      Administering T(1)AM in vivo induces profound hypothermia and bradycardia within
      minutes. T(1)AM treatment also rapidly reduces cardiac output in an ex vivo
      working heart preparation. These results suggest the existence of a new signaling
      pathway, stimulation of which leads to rapid physiological and behavioral
      consequences that are opposite those associated with excess TH.

PMID- 15146181
TI  - Exacerbated graft-versus-host disease in Pirb-/- mice.
AB  - Immune responses are often regulated by opposing receptor pairs that recognize
      the same ligand but deliver either activating or inhibitory signals. Paired
      immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells
      comprise a major histocompatibility complex class I recognition system that
      regulates the responsiveness of these cells. Here, activating PIR-A and
      inhibitory PIR-B bound various mouse major histocompatibility complex class I (H
      2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A
      on macrophages induced intracellular phosphotyrosine signaling. After transfer of
      allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated
      graft-versus-host disease, which was due to augmented activation of recipient
      dendritic cells with concomitant upregulation of PIR-A and increased interferon
      gamma production. PIR-A-induced dendritic cell activation also led to increased
      proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting
      receptors that are essential for successful tissue transplantation and may
      regulate irrelevant reaction to autologous tissues in a constitutive way in
      physiological conditions.

PMID- 15146182
TI  - Delta-like 1 is necessary for the generation of marginal zone B cells but not T
      cells in vivo.
AB  - Notch receptors and their ligands contribute to many developmental systems, but
      it is not apparent how they function after birth, as their null mutants develop
      severe defects during embryogenesis. Here we used the Cre-loxP system to delete
      the Delta-like 1 gene (Dll1) after birth and demonstrated the complete
      disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T
      cell development was unaffected. These results demonstrated that Dll1 was
      dispensable as a ligand for Notch1 at the branch point of T cell-B cell
      development but was essential for the generation of marginal zone B cells. Thus,
      Notch signaling is essential for lymphocyte development in vivo, but there is a
      redundancy of Notch-Notch ligand signaling that can drive T cell development
      within the thymus.

PMID- 15146183
TI  - Acute myeloid leukemia induced by graded reduction of a lineage-specific
      transcription factor, PU.1.
AB  - Transcription factors are believed to have a dominant role in acute myeloid
      leukemia (AML). This idea is supported by analysis of gene-knockout mice, which
      uncovered crucial roles of several transcription factors in normal hematopoiesis,
      and of individuals with leukemia, in whom transcription factors are frequently
      downregulated or mutated. However, analysis of knockout animals has not shown a
      direct link between abrogated transcription factors and the pathogenesis of AML.
      Sfpi1, encoding the lineage-specific transcription factor PU.1, is indispensable
      for normal myeloid and lymphoid development. We found that mice carrying
      hypomorphic Sfpi1 alleles that reduce PU.1 expression to 20% of normal levels,
      unlike mice carrying homo- or heterozygous deletions of Sfpi1, developed AML.
      Unlike complete or 50% loss, 80% loss of PU.1 induced a precancerous state
      characterized by accumulation of an abnormal precursor pool retaining
      responsiveness to G-CSF with disruption of M- and GM-CSF pathways. Malignant
      transformation was associated with a high frequency of clonal chromosomal
      changes. Retroviral restoration of PU.1 expression rescued myeloid
      differentiation of mutant progenitors and AML blasts. These results suggest that
      tightly graded reduction, rather than complete loss, of a lineage-indispensable
      transcription factor can induce AML.

PMID- 15146184
TI  - Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine
      expansions in fly and mouse models of Huntington disease.
AB  - Huntington disease is one of nine inherited neurodegenerative disorders caused by
      a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate
      abnormally in intracellular aggregates. Here we show that mammalian target of
      rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models,
      transgenic mice and human brains. Sequestration of mTOR impairs its kinase
      activity and induces autophagy, a key clearance pathway for mutant huntingtin
      fragments. This protects against polyglutamine toxicity, as the specific mTOR
      inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell
      models of Huntington disease, and inhibition of autophagy has the converse
      effects. Furthermore, rapamycin protects against neurodegeneration in a fly model
      of Huntington disease, and the rapamycin analog CCI-779 improved performance on
      four different behavioral tasks and decreased aggregate formation in a mouse
      model of Huntington disease. Our data provide proof-of-principle for the
      potential of inducing autophagy to treat Huntington disease.

PMID- 15146185
TI  - NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins
      and fly Nipped-B, is mutated in Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a multiple malformation disorder
      characterized by dysmorphic facial features, mental retardation, growth delay and
      limb reduction defects. We indentified and characterized a new gene, NIPBL, that
      is mutated in individuals with CdLS and determined its structure and the
      structures of mouse, rat and zebrafish homologs. We named its protein product
      delangin. Vertebrate delangins have substantial homology to orthologs in flies,
      worms, plants and fungi, including Scc2-type sister chromatid cohesion proteins,
      and D. melanogaster Nipped-B. We propose that perturbed delangin function may
      inappropriately activate DLX genes, thereby contributing to the proximodistal
      limb patterning defects in CdLS. Genome analyses typically identify individual
      delangin or Nipped-B-like orthologs in diploid animal and plant genomes. The
      evolution of an ancestral sister chromatid cohesion protein to acquire an
      additional role in developmental gene regulation suggests that there are
      parallels between CdLS and Roberts syndrome.

PMID- 15146187
TI  - Frequency-dependent modulation of dopamine release by nicotine.
AB  - Although nicotine activation of dopamine release is implicated in addiction, it
      also desensitizes nicotinic acetylcholine receptors (nAChRs), leading to a
      prolonged depression of evoked dopamine release. Here we show that nicotine's
      effects depend on the firing pattern of dopamine neurons, so that while
      desensitization of nAChRs indeed curbs dopamine released by stimuli emulating
      tonic firing, it allows a rapid rise in dopamine from stimuli emulating phasic
      firing patterns associated with incentive/salience paradigms. Nicotine may thus
      enhance the contrast of dopamine signals associated with behavioral cues.

PMID- 15146186
TI  - Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of
      Drosophila melanogaster Nipped-B.
AB  - Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited
      multisystem developmental disorder characterized by growth and cognitive
      retardation; abnormalities of the upper limbs; gastroesophageal dysfunction;
      cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and
      characteristic facial features. Genital anomalies, pyloric stenosis, congenital
      diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self
      injurious tendencies also frequently occur. Prevalence is estimated to be as high
      as 1 in 10,000 (ref. 4). We carried out genome-wide linkage exclusion analysis in
      12 families with CdLS and identified four candidate regions, of which chromosome
      5p13.1 gave the highest multipoint lod score of 2.7. This information, together
      with the previous identification of a child with CdLS with a de novo
      t(5;13)(p13.1;q12.1) translocation, allowed delineation of a 1.1-Mb critical
      region on chromosome 5 for the gene mutated in CdLS. We identified mutations in
      one gene in this region, which we named NIPBL, in four sporadic and two familial
      cases of CdLS. We characterized the genomic structure of NIPBL and found that it
      is widely expressed in fetal and adult tissues. The fly homolog of NIPBL, Nipped
      B, facilitates enhancer-promoter communication and regulates Notch signaling and
      other developmental pathways in Drosophila melanogaster.

PMID- 15146188
TI  - Nicotine amplifies reward-related dopamine signals in striatum.
AB  - Reward-seeking behaviors depend critically on dopamine signaling--dopamine
      neurons encode reward-related information by switching from tonic to phasic
      (burst-like) activity. Using guinea pig brain slices, we show that nicotine, like
      cocaine and amphetamine, acts directly in striatum where it enhances dopamine
      release during phasic but not tonic activity. This amplification provides a
      mechanism for nicotine facilitation of reward-related dopamine signals, including
      responses to other primary reinforcers that govern nicotine dependence in
      smokers.

PMID- 15146189
TI  - Placebo-responsive Parkinson patients show decreased activity in single neurons
      of subthalamic nucleus.
AB  - Placebo administration is known to affect the brain both in pain and in Parkinson
      disease. Here we show that placebo treatment caused reduced activity in single
      neurons in the subthalamic nucleus of placebo-responsive Parkinsonian patients.
      These changes in activity were tightly correlated with clinical improvement; no
      decrease in activity occurred when the clinical placebo response was absent.

PMID- 15146190
TI  - A single in-vivo exposure to delta 9THC blocks endocannabinoid-mediated synaptic
      plasticity.
AB  - Endogenous cannabinoids (eCB) mediate synaptic plasticity in brain regions
      involved in learning and reward. Here we show that in mice, a single in-vivo
      exposure to Delta 9-tetrahydrocannabinol (THC) abolishes the retrograde signaling
      that underlies eCB-mediated synaptic plasticity in both nucleus accumbens (NAc)
      and hippocampus in vitro. This effect is reversible within 3 days and is
      associated with a transient modification in the functional properties of
      cannabinoid receptors.

PMID- 15146191
TI  - Selective neural representation of objects relevant for navigation.
AB  - As people find their way through their environment, objects at navigationally
      relevant locations can serve as crucial landmarks. The parahippocampal gyrus has
      previously been shown to be involved in object and scene recognition. In the
      present study, we investigated the neural representation of navigationally
      relevant locations. Healthy human adults viewed a route through a virtual museum
      with objects placed at intersections (decision points) or at simple turns (non
      decision points). Event-related functional magnetic resonance imaging (fMRI) data
      were acquired during subsequent recognition of the objects in isolation. Neural
      activity in the parahippocampal gyrus reflected the navigational relevance of an
      object's location in the museum. Parahippocampal responses were selectively
      increased for objects that occurred at decision points, independent of
      attentional demands. This increase occurred for forgotten as well as remembered
      objects, showing implicit retrieval of navigational information. The automatic
      storage of relevant object location in the parahippocampal gyrus provides a part
      of the neural mechanism underlying successful navigation.

PMID- 15146192
TI  - Functional proteomic screens reveal an essential extracellular role for hsp90
      alpha in cancer cell invasiveness.
AB  - Tumour cell invasiveness is crucial for cancer metastasis and is not yet
      understood. Here we describe two functional screens for proteins required for the
      invasion of fibrosarcoma cells that identified the molecular chaperone heat shock
      protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed
      extracellularly where it interacts with the matrix metalloproteinase 2 (MMP2).
      Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and
      invasiveness. This role for extracellular hsp90 alpha in MMP2 activation
      indicates that cell-impermeant anti-hsp90 drugs might decrease invasiveness
      without the concerns inherent in inhibiting intracellular hsp90.

PMID- 15146193
TI  - Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid
      cohesion and DNA recombination.
AB  - Sister chromatid cohesion ensures the faithful segregation of chromosomes in
      mitosis and in both meiotic divisions. Meiosis-specific components of the cohesin
      complex, including the recently described SMC1 isoform SMC1 beta, were suggested
      to be required for meiotic sister chromatid cohesion and DNA recombination. Here
      we show that SMC1 beta-deficient mice of both sexes are sterile. Male meiosis is
      blocked in pachytene; female meiosis is highly error-prone but continues until
      metaphase II. Prophase axial elements (AEs) are markedly shortened, chromatin
      extends further from the AEs, chromosome synapsis is incomplete, and sister
      chromatid cohesion in chromosome arms and at centromeres is lost prematurely. In
      addition, crossover-associated recombination foci are absent or reduced, and
      meiosis-specific perinuclear telomere arrangements are impaired. Thus, SMC1 beta
      has a key role in meiotic cohesion, the assembly of AEs, synapsis, recombination,
      and chromosome movements.

PMID- 15146194
TI  - Mechanical stress activates angiotensin II type 1 receptor without the
      involvement of angiotensin II.
AB  - The angiotensin II type 1 (AT1) receptor has a crucial role in load-induced
      cardiac hypertrophy. Here we show that the AT1 receptor can be activated by
      mechanical stress through an angiotensin-II-independent mechanism. Without the
      involvement of angiotensin II, mechanical stress not only activates extracellular
      signal-regulated kinases and increases phosphoinositide production in vitro, but
      also induces cardiac hypertrophy in vivo. Mechanical stretch induces association
      of the AT1 receptor with Janus kinase 2, and translocation of G proteins into the
      cytosol. All of these events are inhibited by the AT1 receptor blocker
      candesartan. Thus, mechanical stress activates AT1 receptor independently of
      angiotensin II, and this activation can be inhibited by an inverse agonist of the
      AT1 receptor.

PMID- 15146195
TI  - Time-controlled transcardiac perfusion cross-linking for the study of protein
      interactions in complex tissues.
AB  - Because of their sensitivity to solubilizing detergents, membrane protein
      assemblies are difficult to study. We describe a protocol that covalently
      conserves protein interactions through time-controlled transcardiac perfusion
      cross-linking (tcTPC) before disruption of tissue integrity. To validate tcTPC
      for identifying protein-protein interactions, we established that tcTPC allowed
      stringent immunoaffinity purification of the gamma-secretase complex in high salt
      concentrations and detergents and was compatible with mass spectrometric
      identification of cross-linked aph-1, presenilin-1 and nicastrin. We then applied
      tcTPC to identify more than 20 proteins residing in the vicinity of the cellular
      prion protein (PrPC), suggesting that PrP is embedded in specialized membrane
      regions with a subset of molecules that, like PrP, use a
      glycosylphosphatidylinositol anchor for membrane attachment. Many of these
      proteins have been implicated in cell adhesion/neuritic outgrowth, and harbor
      immunoglobulin C2 and fibronectin type III-like motifs.

PMID- 15146196
TI  - Fusion proteins comprising a Fusarium-specific antibody linked to antifungal
      peptides protect plants against a fungal pathogen.
AB  - In planta expression of recombinant antibodies recognizing pathogen-specific
      antigens has been proposed as a strategy for crop protection. We report the
      expression of fusion proteins comprising a Fusarium-specific recombinant antibody
      linked to one of three antifungal peptides (AFPs) as a method for protecting
      plants against fungal diseases. A chicken-derived single-chain antibody specific
      to antigens displayed on the Fusarium cell surface was isolated from a pooled
      immunocompetent phage display library. This recombinant antibody inhibited fungal
      growth in vitro when fused to any of the three AFPs. Expression of the fusion
      proteins in transgenic Arabidopsis thaliana plants conferred high levels of
      protection against Fusarium oxysporum f.sp. matthiolae, whereas plants expressing
      either the fungus-specific antibody or AFPs alone exhibited only moderate
      resistance. Our results demonstrate that antibody fusion proteins may be used as
      effective and versatile tools for the protection of crop plants against fungal
      infection.

PMID- 15146197
TI  - Transcriptome characterization elucidates signaling networks that control human
      ES cell growth and differentiation.
AB  - Human embryonic stem (hES) cells hold promise for generating an unlimited supply
      of cells for replacement therapies. To characterize hES cells at the molecular
      level, we obtained 148,453 expressed sequence tags (ESTs) from undifferentiated
      hES cells and three differentiated derivative subpopulations. Over 32,000
      different transcripts expressed in hES cells were identified, of which more than
      16,000 do not match closely any gene in the UniGene public database. Queries to
      this EST database revealed 532 significantly upregulated and 140 significantly
      downregulated genes in undifferentiated hES cells. These data highlight changes
      in the transcriptional network that occur when hES cells differentiate. Among the
      differentially regulated genes are several components of signaling pathways and
      transcriptional regulators that likely play key roles in hES cell growth and
      differentiation. The genomic data presented here may facilitate the derivation of
      clinically useful cell types from hES cells.

PMID- 15146198
TI  - Production of very long chain polyunsaturated omega-3 and omega-6 fatty acids in
      plants.
AB  - We report the production of two very long chain polyunsaturated fatty acids,
      arachidonic acid (AA) and eicosapentaenoic acid (EPA), in substantial quantities
      in a higher plant. This was achieved using genes encoding enzymes participating
      in the omega3/6 Delta8 -desaturation biosynthetic pathways for the formation of
      C20 polyunsaturated fatty acids. Arabidopsis thaliana was transformed
      sequentially with genes encoding a Delta9 -specific elongating activity from
      Isochrysis galbana, a Delta8 -desaturase from Euglena gracilis and a Delta5 
      desaturase from Mortierella alpina. Instrumental in the successful reconstitution
      of these C20 polyunsaturated fatty acid biosynthetic pathways was the I. galbana
      C18-Delta9 -elongating activity, which may bypass rate-limiting steps present in
      the conventional Delta6 -desaturase/elongase pathways. The accumulation of EPA
      and AA in transgenic plants is a breakthrough in the search for alternative
      sustainable sources of fish oils.

PMID- 15146200
TI  - [Human tissue bank for research].

PMID- 15146199
TI  - Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal
      factor.
AB  - Mass spectrometry (MS) analysis is applicable to a broad range of biological
      analytes and has the important advantage that it does not require analytes to be
      labeled. A drawback of MS methods, however, is the need for chromatographic steps
      to prepare the analyte, precluding MS from being used in chemical screening and
      rapid analysis. Here, we report that surfaces that are chemically tailored for
      characterization by matrix-assisted laser-desorption ionization time-of-flight MS
      eliminate the need for sample processing and make this technique adaptable to
      parallel screening experiments. The tailored substrates are based on self
      assembled monolayers that present ligands that interact with target proteins and
      enzymes. We apply this method to screen a chemical library against protease
      activity of anthrax lethal factor, and report a compound that inhibits lethal
      factor activity with a K(i) of 1.1 microM and blocks the cleavage of MEK1 in 293
      cells.

PMID- 15146201
TI  - [The microarray revolution in biomedical research: types of platforms, uses and
      perspectives in oncology].
AB  - Through the introduction, use and management of genome-based tools, research into
      genetic alterations that give rise to diseases as common as cancer has undergone
      a technical revolution comparable to the introduction of the microscope in
      laboratories. Now, study of the gene-disease relationship is no longer based on
      analysing a single gene and its effects, but on analysing the behaviour of
      thousands of genes in a simultaneous form. These systems, generically called
      matrices, arrays, microarrays or biochips, are changing the way we pose problems
      and draw conclusions from experiments, since they offer us a complex photo of the
      genome as a whole. Analyses of expression through microarrays of cDNI or oligos
      are now accessible to the Spanish scientific community. The results have proved
      fascinating to researchers since they can be reproduced easily and contribute a
      great quantity of information on the regulation of the gene expression in normal
      and pathological conditions.

PMID- 15146202
TI  - [State of methicillin resistant Staphylococcus aureus in the Hospital of Navarre
      (2000-2002)].
AB  - BACKGROUND: The aim of the present paper was to determine the prevalence and
      characteristics shown by isolations of Methicillin Resistant Staphylococcus
      Aureus, isolated in our Microbiology Service. METHODS: Retrospective study,
      covering the years 2000, 2001 and 2002. Analysis was made of the origin of the
      infection (nosocomial or non-nosocomial), the unit of origin in the event of
      nosocomial origin, anatomical localisation of the sample, and pattern of
      antibiotic sensitivity. RESULTS: The isolations of Methicillin Resistant
      Staphylococcus aureus accounted for 7.88% of the Staphylococcus aureus isolated.
      Less than half of the strains (44.87%) had a nosocomial origin and were most
      often isolated in the exudates of wounds. With respect to the pattern of
      resistance, there was some 50% of resistance to erythromycin, some 43.60% to
      clindamycine and some 21.79% to mupirocin. CONCLUSIONS: The prevalence and
      resistance pattern in vitro of the isolations of Methicillin Resistant
      Staphylococcus Aureus in our hospital are lower than that published in other
      areas of Spain.

PMID- 15146203
TI  - [Prevalence of microalbuminuria in a hypertensive population of northerm Navarre
      and its relation to other cardiovascular risk factors].
AB  - AIM: To determine the prevalence of microalbuminuria in a hypertense population
      in northern Navarre and its relationship to other cardiovascular risk factors.
      PATIENTS AND METHODS: All the known hypertensive patients in our area of work
      were included, and a transversal study was designed that also evaluated the
      presence of other cardiovascular risk factors, including diabetes mellitus,
      hypercholesterolemia, obesity, smoking and alcohol drinking. RESULTS: A total of
      106 hypertensive patients (54.7% women) were studied. The presence of
      microalbuminuria was found in 19 patients (18%), and a significant percentage
      showed other cardiovascular risk factors - diabetes mellitus (24.5%),
      hypercholesterolemia (61.3%), and obesity (49%). In 12.2% there was a concurrence
      of arterial hypertension, diabetes mellitus, hypercholesterolemia and obesity.
      Eighty-four percent of the diabetics were type 2. The highest percentage of
      cardiovascular risk factors corresponded to the group of hypertensive patients
      with positive microalbuminuria, and the most significant differences were found
      in the group of diabetics. CONCLUSIONS: The frequency of microalbuminuria in our
      hypertensive population was similar to that reported in other papers. A high
      prevalence of cardiovascular risk factors was found, especially in the group of
      hypertensive patients with positive microalbuminuria.

PMID- 15146204
TI  - [Antibiotic sensitivity and treatment recommendations for Streptococcus
      pneumoniae].
AB  - The aims of present paper were to determine the susceptibility of the strains to
      the most usual antibiotics in clinical practice and to review the current
      recommendations to guide the most appropriate treatment. During the period
      october 2000 to september 2002, the patient's data (age and sex), source of the
      sample, diagnosis and antibiotic susceptibility were collected on Streptococcus
      pneumoniae isolates from microbiology laboratories in the Navarra region (555.829
      inhabitants). Four hundred and sixty five isolates were identified (166 from
      invasive infections). Generally, isolates from ear swabs were the most resistant
      to the antimicrobials tested, while those from blood culture were the most
      susceptible. Of the Streptococcus pneumoniae tested, 43% were resistant to
      penicillin, 6.1% to amoxicillin and 6.6% to cefotaxime. Of the 36.3% of
      Streptococcus pneumoniae isolates that were resistant to erythromycin, 85.45%
      exhibited the MLSB phenotype while the remaining 14.55% presented with the M
      phenotype. Multiple-resistance was detected in 32.3% of the strains. The
      antibiotic resistance rates to beta-lactams (specially penicillin, amoxicillin
      and cefotaxime/ceftrixone) in Streptococcus pneumoniae don't prevent its clinical
      use for the most of Streptococcus pneumoniae isolated in our area, except for
      pneumococcal meningitis.

PMID- 15146205
TI  - [Active immunotherapy in the treatment of haematological neoplasias].
AB  - The continuous search for therapeutic approaches that improve the conventional
      treatments of neoplasms, together with an improved understanding of the immune
      system, has led in recent years to the development of Immunotherapy. Basically, a
      distinction can be made between two forms of immunotherapy: passive
      immunotherapy, which consists in the transfer of antibodies or cells previously
      generated in vitro that are directed against the tumour, and active
      immunotherapy, which attempts to activate in vivo the immune system and induce it
      to elaborate a specific response against the tumor antibodies. Hematological
      neoplasms, specifically some B lymphomas, express in their membrane an
      immunoglobulin that is considered a specific antigen of the tumour, which is why
      these diseases have become the ideal target for immunotherapy treatments. There
      are many alternatives, ranging from protein vaccines, which have already shown
      clinical benefits, to those of the second generation, which make use of the new
      techniques of molecular biology to increase the efficacy of the vaccines and
      obtain their production in a quicker and less costly way, but with which there
      are not yet definitive clinical results.

PMID- 15146206
TI  - [Multislice CT of the heart: clinical applications].
AB  - Since the introduction of last generation multislice MSCT systems and the
      development of simultaneous electrocardiographic-tracing image acquisition and
      retrospective reconstruction techniques into clinical routine, cardiac MSCT has
      been considered a very useful non-invasive technique for the study of cardiac
      pathology in the daily clinical practice. One of the main clinical applications
      of this diagnostic technique is the evaluation of the coronary arteries including
      detection and quantification of coronary calcium, multislice CT coronary
      angiography (anatomy, anatomical variants and anomalies of the origin and
      course), the angiographic evaluation of the patency of aortocoronary by-pass
      grafts and coronary stents, and plaque characterization. The new reconstruction
      and postprocessing programs allow to obtain, in addition, parameters of
      myocardial morphology and contraction and cardiac function. Other clinical
      applications include the characterization of cardiac masses and the evaluation of
      the pericardium.

PMID- 15146208
TI  - [Crypreservation of biological samples unit].

PMID- 15146207
TI  - [Neurological tissue bank for research in neuroscience. A reality in Navarre].

PMID- 15146209
TI  - [Compulsory Diseases Notification (CDN) in Navarre 2003].
AB  - Epidemiological vigilance in Navarre covers 34 transmissible diseases, whose
      notification is compulsory, and epidemic outbreaks of any aetiology. Notification
      is carried out on a weekly basis by the doctors from paediatrics, primary and
      specialised level who suspect or diagnose any of these diseases. In 2003, 75.0%
      of all the possible notification reports (a weekly report for each doctor) were
      received, a percentage that has improved in the last five year period. In 2003,
      Influenza reached a rate of 48.9 cases per 1,000 inhabitants (Epidemic Index, EI:
      0.91), showing an epidemic peak in January and another in November. The rate of
      respiratory tuberculosis was 11.76 cases per 100,000 inhabitants, and the rate of
      non-respiratory tuberculosis was 1.90, with a continuous trend to decrease in
      both cases. Five cases of tuberculosis occurred in two small family outbreaks.
      Thirty percent of the cases were produced in immigrants. The cases coinfected
      with HIV have fallen from 21% in 1996 to 2.5% in 2003. Fifteen cases of
      meningococcal disease were reported, (2.6 cases per 100,000 inhabitants),
      appearing in a sporadic form. Neisseria meningitidis serogroup B was isolated in
      10 cases, and serogroup C in 5 cases. Eighty percent appeared in the form of
      sepsis, and death occurred in one case (6.7%). All of the cases younger than six
      years of age were vaccinated and belonged to serogroup B. The incidence of
      Legionnaire's disease was 3.8 cases per 100,000 inhabitants (EI: 0.92), without
      any epidemiological relation between them. There were 7 cases of malaria, all
      imported. The incidence of food borne infections has fallen (EI: 0.71).

PMID- 15146210
TI  - [Accidental hypothermia due to generalized psoriasis].
AB  - The accidental hypothermia is a disorder of corporal termoregulation, defined as
      a central temperature below 35 masculine C. According to the intensity may be
      classified in mild (35-32.2 masculine C), moderate (32.2-28 masculine C) and
      severe (below 28 masculine C). The most frequent causes are the exposure to cold,
      use of depressant drugs of central nervous system and hypoglycemia, although
      there are other less frequent. We present a case of moderate hypothermia due to
      generalized psoriasis which required admission in the Intensive Care Unit of
      Hospital Garcia Orcoyen. The termoregulation, pathogenesis, pathophysiology,
      diagnosis and management of accidental hypothermia are reviewed.

PMID- 15146211
TI  - [Paraneoplasic polyneuropathy with anti-amphiphysin antibodies].
AB  - Paraneoplastic neurological syndromes consist of a dysfunction of any part of the
      nervous system, in isolation or in combination, caused by a malign neoplasia, but
      not by the direct tissular or metastasic invasion of the tumour. Their pathogeny
      is explained by immunological mechanisms and they are characterised by the
      presence of high rates of antibodies in serum and cerebrospinal fluid. We present
      the case of a patient with a sensitive neuropathy that produced ataxia, and who
      suffered from a poorly differentiated adenocarcinoma of the lung, in whom the
      search for antineuronal antibodies was positive for antiamphiphysin antibodies,
      supporting the diagnosis of paraneoplastic polyneuropathy.

PMID- 15146212
TI  - [Working for patient safety: starting teamwork on medication errors].

PMID- 15146213
TI  - [Treatment of osteoporosis: heterogeneous, inefficient and lacking in scientific
      evidence?].

PMID- 15146214
TI  - NTP technical report on the toxicity studies of 2- and 4-Methylimidazole (CAS No.
      693-98-1 and 822-36-6) administered in feed to F344/N rats and B6C3F1 mice.
AB  - [Structure-see text] 2-Methylimidazole and 4-methylimidazole are
      intermediate/starting materials or components in the manufacture of
      pharmaceuticals, photographic and photothermographic chemicals, dyes and
      pigments, agricultural chemicals, and rubber; these chemicals have been
      identified as undesirable by-products in several foods and have been detected in
      mainstream and sidestream tobacco smoke. The National Cancer Institute nominated
      2- and 4-methylimidazole as candidates for toxicity and carcinogenicity studies.
      Toxicity studies were carried out in male and female F344/N rats and B6C3F1 mice.
      Animals were exposed to 2- or 4-methylimidazole in feed for 15 days or 14 weeks;
      clinical pathology studies were conducted in the 14-week studies on days 8, 29,
      and 86 and at week 14. Genetic toxicity studies were conducted in Salmonella
      typhimurium, rat and mouse bone marrow, and mouse peripheral blood. Groups of
      five male and five female rats and mice were fed diets containing 0, 1,200,
      3,300, or 10,000 ppm 2-methylimidazole (equivalent to average daily doses of
      approximately 115, 290, or 770 mg 2-methylimidazole/ kg body weight to rats; 220,
      640, or 2,100 mg/kg to male mice; 300, 800, or 2,400 to female mice) for 15 days.
      Groups of five male and five female rats and mice were fed diets containing 0,
      300, 800, or 2,500 ppm 4-methylimidazole (equivalent to average daily doses of
      approximately 30, 80, or 220 mg/kg for rats and 65, 170, or 500 mg/kg for mice)
      for 15 days. In the 15-day 2-methylimidazole studies, all animals survived to the
      end of the studies. The mean body weights of 10,000 ppm male rats and female mice
      were significantly less than those of the controls. Feed consumption by 10,000
      ppm male and female rats was reduced. Enlarged thyroid glands were observed in
      3,300 and 10,000 ppm male and female rats. The incidences of diffuse hyperplasia
      of follicular cells of the thyroid gland in 3,300 and 10,000 ppm male and female
      rats and pars distalis hypertrophy of the pituitary gland in 3,300 and 10,000 ppm
      males and 10,000 ppm females were increased compared to the controls. In all
      exposed groups of male and female mice, the incidences and severities of
      follicular cell hypertrophy of the thyroid gland and the severities of
      hematopoietic cell proliferation of the spleen generally increased with
      increasing exposure concentration. In the 4-methylimidazole studies, all animals
      survived to the end of the studies, and there were no significant differences in
      mean body weights, clinical findings, organ weights, or gross or microscopic
      lesions between exposed and control groups. Groups of 10 male and 10 female rats
      and mice were fed diets containing 0, 625, 1,250, 2,500, 5,000, or 10,000 ppm 2-
      or 4-methylimidazole (equivalent to average daily doses of approximately 40, 80,
      160, 300, or 560 mg/kg 2- or 4-methylimidazole to rats; and 100, 165, 360, 780,
      or 1,740 mg/kg 2-methylimidazole or 100, 240, 440, 915, or 1,840 mg/kg 4
      methylimidazole to male mice; and 90, 190, 400, 800, or 1,860 mg/kg 2
      methylimidazole or 110, 240, 540, 1,130, or 3,180 mg/kg 4-methylimidazole to
      females) for 14 weeks. All animals survived to the end of the 14-week 2
      methylimidazole studies. Compared to the controls, the mean body weights were
      significantly decreased in groups of male rats and mice exposed to 2,500 ppm or
      greater and in 5,000 and 10,000 ppm female rats and mice. In rats, 2
      methylimidazole induced a transient erythrocytosis in females and a minimal,
      exposure concentration-related, microcytic, normochromic, nonresponsive anemia. 2
      Methylimidazole increased thyroid-stimulating hormone concentrations and
      decreased thyroxine and triiodothyronine concentrations of male and female rats
      in an exposure concentration-related manner. 2-Methylimidazole induced a mild to
      moderate, exposure concentration-related, macrocytic, hyperchromic, responsive
      anemia in mice. Triiodothyronine concentrations were increased in exposed male
      and female mice, and thyroxine concentrations were decreased in exposed females.
      Relative to the control groups, clinical chemistry evaluations on day 29 and at
      week 14 identified decreases in alanine aminotransferase concentrations and total
      protein and albumin concentrations of rats. In the 2-methylimidazole studies,
      absolute spleen weights were significantly increased in all exposed groups of
      male rats. The heart and liver weights were increased in all exposed groups of
      male mice, as were the spleen weights of female mice exposed to 2,500 ppm or
      greater. Spermatid heads per testis and mean spermatid count were significantly
      decreased in 10,000 ppm male rats. The estrous cycle of 10,000 ppm female rats
      was significantly increased. Gross pathology observations included enlarged
      thyroid glands, small uteri, and mottled spleen in 5,000 and 10,000 ppm mice. The
      incidences of diffuse follicular cell hyperplasia of the thyroid gland were
      significantly increased in male rats exposed to 1,250 ppm or greater and female
      rats exposed to 2,500 ppm or greater. The incidence of testicular degeneration
      was significantly increased in 10,000 ppm male rats, and two males in the 10,000
      ppm group had follicular cell adenoma of the thyroid gland. In mice, there were
      generally significant increases in the incidences of follicular cell hypertrophy
      of the thyroid gland, hematopoietic cell proliferation of the spleen, and
      hemosiderin pigmentation of the renal tubule in males exposed to 1,250 ppm or
      greater and females exposed to 2,500 ppm or greater. In the 14-week 4
      methylimidazole studies, one 10,000 ppm male mouse was found dead during week 4,
      and seven 10,000 ppm female mice were found dead during weeks 1 and 2. Mean body
      weights were significantly less than those of the controls for male rats exposed
      to 2,500 ppm or greater, 5,000 and 10,000 ppm female rats, male mice exposed to
      1,250 ppm or greater, and all exposed groups of female mice. Reduced feed
      consumption was observed in 5,000 and 10,000 ppm male and female rats. Clinical
      findings included nasal/eye discharge, ruffled fur, thinness, ataxia, and
      abnormal breathing in rats, and ruffled fur and dull coats in female mice. On
      days 29 and 82, functional observations in 5,000 and 10,000 ppm rats included
      labored or increased respiration, mild tremors, walking on tiptoes, hunched
      posture, piloerection, crouching over, impaired coordination of movement, ataxia,
      and pupillary constriction. 4-Methylimidazole induced a transient erythrocytosis
      and a minimal, exposure concentration-related, microcytic, normochromic,
      nonresponsive anemia in male and female rats. Clinical chemistry evaluations
      generally showed a cholestatic effect in exposed male and female rats. At week
      14, there was a significant decrease in total protein and albumin concentrations
      of female rats exposed to 5,000 or 10,000 ppm. In mice, 4-methylimidazole induced
      a macrocytic, hyperchromic, responsive anemia and, particularly in males,
      increases in triiododthyronine concentrations and transient decreases in
      thyroxine concentrations. In the 4-methylimidazole studies, the liver weights of
      male rats exposed to 2,500 ppm or greater were significantly increased; spleen
      weights of female rats exposed to 2,500 ppm or greater were decreased. The
      absolute liver weight was decreased in 10,000 ppm male mice, and relative weights
      were significantly increased in all exposed groups of mice. In female mice, there
      was a significant decrease in the absolute weights and increase in the relative
      weights of the heart, right kidney, and liver in groups exposed to 2,500 ppm or
      greater. The epididymal spermatozoal concentration was significantly increased in
      5,000 ppm male rats. Gross pathology observations included pale livers in male
      rats exposed to 2,500 ppm or greater and small testes and uteri in 10,000 ppm
      male and female rats. Microscopic analysis identified significantly increased
      incidences of cytoplasmic hepatocyte vacuolization of the liver of male rats
      exposed to 2,500 ppm or greater and 10,000 ppm female rats, hypospermia of the
      epididymis in 10,000 ppm male rats, atrophy and inflammation of the prostate
      gland in 10,000 ppm male rats, and degeneration of the testes in 5,000 and 10,000
      ppm male rats. 2-Methylimidazole and 4-methylimidazole were negative in the S.
      typhimurium mutation assay when tested in strains TA97, TA98, TA100, and TA1535,
      with and without S9 activation enzymes. Testing of 2-methylimidazole in vivo for
      induction of chromosomal damage, as measured by micronucleated erythrocyte
      frequency, produced mixed results. When administered by intraperitoneal injection
      three times at 24-hour intervals, 2-methylimidazole produced negative results in
      bone marrow micronucleus tests in rats and mice. However, in the 14-week study of
      2-methylimidazole, a significant exposure-related increase in the frequency of
      micronucleated normochromatic erythrocytes was noted in peripheral blood of male
      and female mice. In vivo, 4-methylimidazole produced uniformly negative results
      in three-injection bone marrow micronucleus tests in rats and mice and in 14-week
      peripheral blood micronucleus tests in male and female mice.

PMID- 15146215
TI  - NTP technical report on the toxicology and carcinogenesis studies of propylene
      glycol mono-t-butyl ether (CAS No. 57018-52-7) in F344/N rats and B6C3F1 mice and
      a toxicology study of propylene glycol mono-t-butyl ether in male NBR rats
      (inhalation studies).
AB  - BACKGROUND: Propylene glycol mono-t-butyl ether is used as a solvent in all
      purpose cleaners, inks, and nail polish lacquers. We studied the effects of
      propylene glycol mono-t-butyl ether on male and female rats to identify potential
      toxic or cancer-related hazards to humans. METHODS: We exposed groups of male and
      female rats and mice to air containing vapors of propylene glycol mono-t-butyl
      ether at concentrations of 75, 300, or 1,200 parts per million (ppm) for 6 hours
      per day, 5 days a week for 2 years. Untreated control animals were housed in
      similar exposure chambers but without chemical exposure for comparison. Tissues
      from more than 40 sites were examined for every animal. RESULTS: Rats receiving
      1,200 ppm propylene glycol mono-t-butyl ether weighed less on average than the
      control animals. Tumors were seen in the liver and kidney of a few male rats
      exposed to propylene glycol mono-t-butyl ether. No increases in the numbers of
      tumors were seen in female rats. In male and female mice there were large
      increases in the numbers of liver tumors compared with the control animals.
      CONCLUSIONS: We conclude that propylene glycol mono-t-butyl ether caused cancer
      in the liver of male and female mice. Propylene glycol mono-t-butyl ether did not
      cause cancer in female rats, and its effect on the liver and kidney of male rats
      was considered uncertain.

PMID- 15146216
TI  - NTP toxicology and carcinogenesis studies of trans-cinnamaldehyde (CAS No. 14371
      10-9) in F344/N rats and B6C3F1 mice (feed studies).
AB  - Cinnamaldehyde is used in foods, beverages, medical products, perfumes,
      cosmetics, soaps, detergents, creams, and lotions. Cinnamaldehyde has been used
      as a filtering agent and a rubber reinforcing agent and is used as a brightener
      in electroplating processes, as an animal repellent, as an insect attractant, and
      as an antifungal agent. trans-cinnamaldehyde was nominated for study by the Food
      and Drug Administration based on its widespread use as a flavor and fragrance
      ingredient and its structural similarity to cinnamyl anthranilate and 3,4,5
      trimethoxy cinnamaldehyde, two known rodent carcinogens. Male and female F344/N
      rats and B6C3F1 mice were exposed to trans-cinnamaldehyde (at least 95% pure) in
      feed for 3 months or 2 years. Genetic toxicology studies were conducted in
      Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila
      melanogaster, and mouse peripheral blood erythrocytes. 3-MONTH STUDY IN RATS:
      Groups of 10 male and 10 female F344/N rats were fed diets containing 4,100,
      8,200, 16,500, or 33,000 ppm microencapsulated trans-cinnamaldehyde (equivalent
      to average daily doses of approximately 275, 625, 1,300, or 4,000 mg trans
      cinnamaldehyde/kg body weight to males and 300, 570, 1,090, or 3,100 mg/kg to
      females) for 3 months. Additional groups of 10 male and 10 female rats received
      untreated feed (untreated controls) or feed containing placebo microcapsules
      (vehicle controls). All rats survived to the end of the study. Mean body weights
      of all exposed groups of males and 16,500 and 33,000 ppm females were
      significantly less than those of the vehicle controls, and 33,000 ppm males lost
      weight during the study. Feed consumption by exposed groups of males and females
      was less than that by the vehicle controls throughout the study. Clinical
      chemistry results of these studies indicated that trans-cinnamaldehyde
      administration, at the doses selected, induced an increase in serum bile acid
      concentration that suggests a hepatic effect in both male and female rats. Gross
      lesions observed at necropsy included multifocal to diffuse white nodules of the
      forestomach mucosa in 8,200 ppm or greater males and females. Increased
      incidences of nonneoplastic lesions of the forestomach included squamous
      epithelial hyperplasia in 8,200 ppm or greater males and females and chronic
      active inflammation in 33,000 ppm males and 16,500 and 33,000 ppm females. 3
      MONTH STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets
      containing 4,100, 8,200, 16,500, or 33,000 ppm microencapsulated trans
      cinnamaldehyde (equivalent to average daily doses of approximately 650, 1,320,
      2,550, and 5,475 mg/kg to males and 625, 1,380, 2,680, and 5,200 mg/kg to
      females) for 3 months. Additional groups of 10 male and 10 female mice received
      untreated feed (untreated controls) or feed containing placebo microcapsules
      (vehicle controls). One vehicle control male, one 4,100 ppm male, and one 33,000
      ppm male died during the first week of the study due to inanition that resulted
      from difficulty with the feeder. Five 16,500 ppm and eight 33,000 ppm male mice
      died during weeks 2 and 3 due to unpalatability of the dosed feed. Mean body
      weights of all exposed groups of males and of females exposed to 8,200 ppm or
      greater were significantly less than those of the vehicle controls. Feed
      consumption by 16,500 and 33,000 ppm mice was less than that by the vehicle
      controls during weeks 1 and 2. The incidence of squamous epithelial hyperplasia
      of the forestomach mucosa in 33,000 ppm females was significantly increased, and
      olfactory epithelial degeneration of the nasal cavity occurred in 16,500 and
      33,000 ppm males and females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50
      female F344/N rats were fed diets containing 1,000, 2,100, or 4,100 ppm
      microencapsulated trans-cinnamaldehyde for 2 years. Additional groups of 50 male
      and 50 female rats received untreated feed (untreated controls) or feed
      containing placebo microcapsules (vehicle controls). Dietary concentrations of
      1,000, 2,100, or 4,100 ppm delivered average daily doses of approximately 50,
      100, or 200 mg/kg to males and females. Survival of 4,100 ppm males was greater
      than that of the vehicle controls. Mean body weights of 4,100 ppm males and
      females were generally less than those of the vehicle controls throughout the
      study. Feed consumption by 2,100 and 4,100 ppm males and 4,100 ppm females was
      less than that by the vehicle controls at the beginning and end of the study.
      There were no neoplasms or nonneoplastic lesions that were attributed to exposure
      to trans-cinnamaldehyde. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female
      B6C3F1 mice were fed diets containing 1,000, 2,100, or 4,100 ppm
      microencapsulated trans-cinnamaldehyde for 2 years. Additional groups of 50 male
      and 50 female mice received untreated feed (untreated controls) or feed
      containing placebo microcapsules (vehicle controls). Dietary concentrations of
      1,000, 2,100, or 4,100 ppm delivered average daily doses of approximately 125,
      270, or 550 mg/kg to males and females. Survival of males in the 2,100 ppm group
      was less than that of the vehicle control group. Mean body weights of 2,100 and
      4,100 ppm males and females were generally less than those of the vehicle
      controls throughout the study, and mean body weights of 1,000 ppm males were less
      after week 74. Feed consumption by exposed mice was similar to that by the
      vehicle controls. The incidences of olfactory epithelial pigmentation in 4,100
      ppm males and in 2,100 and 4,100 females were significantly greater than those in
      vehicle controls. There were no neoplasms that were attributed to exposure to
      trans-cinnamaldehyde. GENETIC TOXICOLOGY: trans-cinnamaldehyde was mutagenic in
      S. typhimurium strain TA100 in the presence of induced mouse liver S9 activation
      enzymes only. All other strain and activation combinations, including the
      standard rat and hamster derived liver S9 fractions yielded negative results.
      trans-cinnamaldehyde induced sister chromatid exchanges in Chinese hamster ovary
      cells with and without induced rat liver S9 activation. No significant increase
      in the frequency of chromosomal aberrations occurred in Chinese hamster ovary
      cells cultured with trans-cinnamaldehyde, with or without induced rat liver S9.
      In tests for induction of germ cell genetic damage in male Drosophila
      melanogaster, trans-cinnamaldehyde induced a significant increase in the
      frequency of sex-linked recessive lethal mutations when administered by abdominal
      injection; however, no induction of reciprocal translocations occurred in germ
      cells of treated males. No increase in the frequency of micronucleated
      erythrocytes was observed in peripheral blood of male or female mice administered
      trans-cinnamaldehyde in dosed feed for 3 months. CONCLUSIONS: Under the
      conditions of this 2-year feed study, there was no evidence of carcinogenic
      activity of transcinnamaldehyde in male or female F344/N rats exposed to 1,000,
      2,100, or 4,100 ppm. There was no evidence of carcinogenic activity of trans
      cinnamaldehyde in male or female B6C3F1 mice exposed to 1,000, 2,100, or 4,100
      ppm. Exposure to trans-cinnamaldehyde resulted in olfactory epithelial
      pigmentation in male and female mice.

PMID- 15146217
TI  - Competing interests.

PMID- 15146218
TI  - Nurse experiences as cancer survivors: part I-personal.
AB  - PURPOSE/OBJECTIVES: To uncover dimensions of nurses' personal experiences of
      cancer survivorship. DESIGN: Interpretive, phenomenologic. SETTING: Metropolitan
      area in the northeastern United States. SAMPLE: 25 RNs diagnosed with cancer.
      Average age was 50 years, and 20 participants were less than five years from
      initial diagnosis. METHODS: Interviews. Analysis using methodology of Newman
      (1994, 1999) and Van Manen (1990). MAIN RESEARCH VARIABLES: Nurses' personal
      experiences of cancer survivorship. FINDINGS: Themes of the nurses' personal
      experiences of survivorship included the shock of becoming a patient and
      multifaceted dimensions of the treatment experience, including time, coordinating
      their own care, the struggle to maintain normalcy, uncertainty, nonclinical self
      care strategies, and encounters with caring and uncaring providers. Participants
      identified the need for supportive relationships both in personal and
      professional arenas throughout the survivorship process. The cancer experience
      became an opportunity for change in priorities. CONCLUSIONS: Although nurse
      cancer survivors experience similar personal vulnerabilities to those of non
      nurses, their vulnerabilities often are affected by their knowledge of the
      healthcare process and content of care with which they are most familiar. They
      also are affected by what they know is at stake. This particular insider
      vulnerability is not cited often in research literature and, therefore, is not
      recognized as a particular type of need that should be addressed in cancer
      survivorship. IMPLICATIONS FOR NURSING: Nurse patients need providers to be
      sensitive to their information and support needs, which may vary because of their
      professional experiences and personal resources. Findings suggest that nurse
      patients may need supportive approaches that target their unique vulnerabilities.

PMID- 15146219
TI  - Nurse experiences as cancer survivors: part II--professional.
AB  - PURPOSE/OBJECTIVES: To uncover dimensions of nurses' professional experiences of
      cancer survivorship. DESIGN: Interpretive, phenomenologic. SETTING: Metropolitan
      area in the northeastern United States. SAMPLE: 25 RNs diagnosed with cancer.
      Average age was 50 years, and 20 participants were less than five years from
      initial diagnosis. METHODS: Interviews. Data were analyzed using the methodology
      of Newman (1994, 1999) and VanManen (1990). MAIN RESEARCH VARIABLES: Nurses'
      professional experiences of cancer survivorship. FINDINGS: Professional
      experiences of cancer survivorship fell into five themes: (a) role ambiguity, (b)
      a deepening level of compassion for patients and others, (c) self-disclosure as a
      therapeutic intervention, (d) becoming an advocate for change, and (e)
      volunteerism. CONCLUSIONS: Cancer survivorship was a factor in reshaping
      participants' clinical practice. Experiencing the role of the patient affirmed
      the necessity of compassionate care for these participants. Nurses experienced a
      deepening level of compassion for patients and used self-disclosure as a
      therapeutic intervention. During and shortly after treatment, role ambiguity
      (being both patient and nurse) could cause difficulties. Nurses took action to
      change their clinical environment through their influence on colleagues and the
      healthcare system and by working through other organizations to improve patient
      care. IMPLICATIONS FOR NURSING: Nurse cancer survivors can benefit from the
      support of colleagues and healthcare providers and an appreciation of the
      challenge of being both a professional and a patient. The invitation for dialogue
      as they return to work may help with the challenges of role ambiguity as nurse
      cancer survivors. Based on this study, nurses value the opportunity to enhance
      care environments with their two-world knowledge through compassionate care,
      disclosure, advocacy, and volunteering, and coworkers need to appreciate each
      nurse's unique response to this potentially life-changing process. Nurses in all
      settings can learn from their cancer survivor colleagues who have been the
      recipients of care to reflect on their own clinical practice in the areas of
      advocacy, sensitivity to patient concerns, and care experiences.

PMID- 15146220
TI  - A process model for evidence-based literature syntheses.
AB  - PURPOSE/OBJECTIVES: To describe the development and implementation of the Triad
      Model of Research Synthesis, developed as a mechanism to produce systematic
      literature reviews that can serve as sources of evidence for decision making in
      health care. DATA SOURCES: Authors' recollections of the development and
      implementation process over a one-year period during 2002. Tracking forms were
      completed by members of three triad teams as they compiled research syntheses on
      clinical topics: pharmacologic treatment of dyspnea, assessment of sleep
      disturbances in patients with cancer, and exercise as an intervention for cancer
      related fatigue. DATA SYNTHESIS: The systematic literature review process
      includes the following steps: (a) organize, search the literature, and focus the
      research synthesis question; (b) critique the selected literature; (c) synthesize
      the evidence; and (d) write. On average, triad members spent hours that were
      equivalent to full-time work during the year (excluding completion of
      manuscripts) on the synthesis projects. Hours spent varied by member role and
      with each phase of the process. CONCLUSIONS: Performing a research synthesis
      using the triad model was a productive and resource-intensive experience that
      points to the need for negotiating resources prior to embarking on such an
      exercise. IMPLICATIONS FOR NURSING: Given a group of highly motivated nurses and
      others with adequate time and resources, this model can be effective when
      developing systematic reviews about a variety of topics. Literature syntheses
      developed can be used as evidence for clinicians and others to develop practice
      protocols and other evidence-based care guidelines.

PMID- 15146221
TI  - The use of nebulized opioids in the management of dyspnea: evidence synthesis.
AB  - PURPOSE/OBJECTIVES: To analyze the evidence about the use of nebulized opioids to
      treat dyspnea using the Priority Symptom Management (PRISM) level-of-evidence
      framework and to make a practice recommendation. DATA SOURCES: Computerized
      database and manual search for articles and abstracts that included experimental
      trials, chart reviews, and case studies. DATA SYNTHESIS: 20 articles with
      evaluable evidence were identified. Analysis was complex because of heterogeneous
      variables and outcome measures. A major limitation is small sample sizes. The
      majority of PRISM level I and II studies indicated unfavorable evidence.
      CONCLUSIONS: Scientific data supporting the use of nebulized opioids to treat
      dyspnea in patients with chronic pulmonary disease, including malignancy, are
      lacking. IMPLICATIONS FOR NURSING: Insufficient data identify a need for further
      research with random crossover designs involving larger samples that are
      stratified according to prior opioid use. Consistency of study variables should
      be emphasized.

PMID- 15146222
TI  - Optimal use of granulocyte-colony-stimulating factor in patients with cancer who
      are at risk for chemotherapy-induced neutropenia.
AB  - PURPOSE/OBJECTIVES: To provide an overview of the risks for and occurrence of
      chemotherapy-induced neutropenia in patients with cancer and its optimal
      prophylactic management with recombinant human granulocyte-colony-stimulating
      factor (G-CSF). DATA SOURCES: Original research, review articles, conference
      presentations, and published guidelines. DATA SYNTHESIS: Chemotherapy-induced
      neutropenia is a common serious adverse event, and the risks for it can be
      predicted on the basis of patient characteristics and the chemotherapy regimen.
      CONCLUSIONS: Optimal, cost-effective prophylactic management of chemotherapy
      induced neutropenia with G-CSF requires the assessment of patient factors and the
      myelotoxicity of the chemotherapy regimen. IMPLICATIONS FOR NURSING: Neutropenia
      and its complications can be serious adverse events in patients who are treated
      with chemotherapy. Nurses should be familiar with how to identify patients who
      are at risk for neutropenia and its complications and should be prepared to
      discuss the need for first-cycle use of G-CSF with the other members of the
      treatment team as necessary.

PMID- 15146223
TI  - Advanced practice nursing in head and neck cancer: implementation of five roles.
AB  - PURPOSE/OBJECTIVES: To apply the five roles of advanced practice nurses (APNs)
      (administrator, educator, clinician, researcher, and consultant) to the
      management of patients with head and neck cancer. DATA SOURCES: Research reports,
      clinical papers, practice guidelines, clinical experience. DATA SYNTHESIS: APNs
      assess, conceptualize, and analyze complex patient data. As represented in the
      five roles, these abilities promote patients' development and implementation of
      survival skills. These roles were integrated into a cancer resource center, a
      collaborative endeavor providing patients, families, and community resources with
      support for coping with the complex issues facing them. CONCLUSIONS: The
      application of the five roles to this specialized nursing area enables patients
      to develop survival skills and can provide a framework for support. IMPLICATIONS
      FOR NURSING: Application of APN roles promotes development and implementation of
      survival skills in patients with head and neck cancer, enhancing their quality
      and quantity of life and improving compliance with treatment.

PMID- 15146224
TI  - Sleep, fatigue, and depressive symptoms in breast cancer survivors and matched
      healthy women experiencing hot flashes.
AB  - PURPOSES/OBJECTIVES: To compare sleep quality and disturbance, fatigue, and
      depressive symptoms between breast cancer survivors and healthy women
      experiencing hot flashes and to examine relationships among sleep and remaining
      variables (fatigue, depressive symptoms, and frequency of hot flashes). DESIGN:
      Cross-sectional, descriptive, comparative pilot study. SETTING: University-based
      outpatient setting. SAMPLE: 15 breast cancer survivors and 15 healthy women
      matched on age, race, and menopausal status. All women had untreated hot flashes
      (no hormone replacement therapy or other hot flash treatments). METHODS:
      Questionnaires (sleep quality and disturbance, fatigue, and depression); two
      ambulatory, 24-hour sternal skin conductance monitoring sessions (hot flash
      frequency); and medical records review. MAIN RESEARCH VARIABLES: Sleep quality
      and disturbance, fatigue, depressive symptoms, and objective hot flash frequency.
      FINDINGS: The majority of participants evidenced poor sleep quality and high
      sleep disturbance (73% of breast cancer survivors and 67% of healthy women above
      a cutoff score of 5). Sleep duration was significantly shorter for breast cancer
      survivors in contrast to healthy women. Nighttime flashes were experienced by 67%
      of breast cancer survivors and 37% of healthy women. No group differences were
      found in fatigue, depressive symptoms, or objective hot flash frequency. Global
      sleep scores were significantly positively correlated with fatigue and depression
      but not with hot flash frequency. CONCLUSIONS: Findings suggest that sleep
      disturbance is common in menopausal breast cancer survivors and healthy women, is
      not necessarily related to hot flashes, and may stem from a multifactorial
      etiology. IMPLICATIONS FOR NURSING: Menopausal breast cancer survivors who
      present with any one of these symptoms should be screened for all symptoms both
      during and after treatment.

PMID- 15146226
TI  - Improving enrollment in cancer clinical trials.
AB  - PURPOSE/OBJECTIVES: To identify successful strategies for clinical trial
      recruitment. DESIGN: Survey research. SETTING: New Jersey institutions actively
      recruiting patients for clinical trials. SAMPLE: 84 clinical research nurses
      directly involved with patient recruitment were surveyed, and 50 responded (60%
      response rate). METHODS: Focus group; 34-item, direct mail questionnaire; follow
      up telephone interviews; and descriptive statistics. MAIN RESEARCH VARIABLES:
      Strategies for patient recruitment and retention. FINDINGS: Respondents agreed
      most strongly about the importance of emphasizing to patients that treatment
      would not be compromised and keeping physicians informed of available protocols.
      Respondents felt the most effective strategies for increasing public awareness of
      clinical trials were to highlight participants in past trials and to stress the
      value of clinical trials through campaigns sponsored by nonprofit organizations.
      Compared to other respondents, those from cancer centers were significantly less
      concerned about educating physicians on the value of clinical trials. Focus group
      and telephone interview participants reported that patient retention in cancer
      trials was a lesser issue because enrollees tend to be motivated to continue.
      CONCLUSIONS: Successful recruitment may depend on how a patient is approached
      about participation, keeping physicians abreast of available trials, and the
      level of awareness the public or a patient has about clinical research prior to
      considering it as a treatment option. IMPLICATIONS FOR NURSING: Research nurses
      often are the first to interact with patients considering clinical trial
      participation and remain involved throughout the trial experience. Depending on
      the research setting, they are likely to be more informed about available
      protocols than physicians. Research nurses are in a position to build rapport
      with and advocate for patients. Strategies to increase enrollment and retention
      should actively involve these key personnel.

PMID- 15146225
TI  - Libido as part of sexuality in female cancer survivors.
AB  - PURPOSE/OBJECTIVES: To present the state of knowledge and a suggested program of
      research related to one part of sexual functioning in female cancer survivors:
      libido. DATA SOURCES: Journal articles, monographs, and book chapters. DATA
      SYNTHESIS: Sexuality is a broadly defined term with many components. Libido is a
      component of sexuality and is reviewed with respect to definition, physiology,
      and measurement. Evidence-based interventions also are discussed. CONCLUSIONS:
      Most of the evidence related to enhancing libido involves testosterone, but this
      has not been tested in cancer survivors. Several clinical questions are yet to be
      answered regarding physiology as well as nonpharmacologic and pharmacologic
      interventions for enhancing libido. IMPLICATIONS FOR NURSING: Nurse researchers
      could add much to the evidence base on interventions for improving libido and,
      subsequently, sexual health. Implementing behavioral interventions to enhance
      libido would be an appropriate nursing function.

PMID- 15146227
TI  - Psychometric evaluation of two scales assessing functional status and peripheral
      neuropathy associated with chemotherapy for ovarian cancer: a gynecologic
      oncology group study.
AB  - PURPOSE/OBJECTIVES: To evaluate the psychometric properties of two adapted
      scales, one for functional status and one for peripheral neuropathy secondary to
      neurotoxic chemotherapy. DESIGN: Repeated measures methodologic design conducted
      within a Gynecologic Oncology Group (GOG) phase III clinical trial that randomly
      assigned patients with advanced epithelial ovarian cancer to cisplatin and
      cyclophosphamide or cisplatin and paclitaxel. SETTING: 8 GOG institutions
      participating in the GOG clinical trial. SAMPLE: 88 evaluable outpatients
      enrolled in the GOG clinical trial. Sample size at time 1 (T1) was 88 patients
      and at time 2 (T2) was 67 patients. METHODS: All scales were administered at T1
      (prior to initiation of chemotherapy) and T2 (after six cycles of chemotherapy
      but prior to second-look laparotomy). Internal consistency reliability, criterion
      validity, and construct validity were evaluated, and clinical application was
      explored. MAIN RESEARCH VARIABLES: Self-reported peripheral neuropathy and
      functional status (comprised of physical function and role function subscales),
      the GOG performance status scale, and the GOG toxicity criteria. FINDINGS:
      Reliability coefficients at T1 were physical function = 0.83, role function =
      0.96, and peripheral neuropathy = 0.91; at T2, they were physical function =
      0.83, role function = 0.92, and peripheral neuropathy = 0.89. At T1, physical
      function and role function correlated positively with performance status.
      Peripheral neuropathy correlated positively with GOG toxicity criteria used at
      T2. Principal component factor analysis suggested that the functional status
      scale had a two-factor structure with factors representing general and specific
      mobility and that the peripheral neuropathy scale also had a two-factor structure
      with factors representing foot and hand neuropathy. CONCLUSIONS: The physical
      function, role function, and peripheral neuropathy scales have internal
      consistency, reliability, criterion validity, and construct validity. However,
      revision of the scales should address modification of specific questions and
      consider increasing the Likert scale from a four-point to a five- or seven-point
      scale to enhance clinical sensitivity and application. IMPLICATIONS FOR NURSING:
      With minor modifications, these scales should be useful in assessing physical
      function, role function, and peripheral neuropathy in patients who receive agents
      that may cause peripheral neuropathy.

PMID- 15146228
TI  - Therapeutic touch, quiet time, and dialogue: perceptions of women with breast
      cancer.
AB  - PURPOSE/OBJECTIVES: To compare the perceptions of women with breast cancer to an
      experimental therapeutic touch (TT) plus dialogue nursing intervention with
      perceptions of a control quiet time plus dialogue nursing intervention. DESIGN:
      Qualitative study based on the Science of Unitary Human Beings. SETTING: Data
      collected as part of a larger experimental study of the effects of TT on pre- and
      postoperative anxiety and mood and postoperative pain in women with breast
      cancer. SAMPLE: 18 women with early-stage breast cancer. METHODS: Telephone
      interviews at the completion of an experimental or control nursing intervention
      administered in the women's homes before and after breast cancer surgery. MAIN
      RESEARCH VARIABLES: Women's perceptions of participation in a study of the
      effects of dialogue and TT or quiet time. FINDINGS: Content analysis of
      transcribed telephone interviews revealed few differences in participants'
      perceptions of experimental and control interventions. Only participants who
      received the experimental intervention reported body sensations, and only
      participants in the control group inquired about the study and its purpose.
      Regardless of experimental or control intervention participation, women expressed
      feelings of calmness, relaxation, security, and comfort and a sense of awareness.
      The few women who commented about the nurse who administered the experimental or
      control intervention indicated that the nurse was empathetic, concerned,
      supportive, or helpful. CONCLUSIONS: The women regarded either nursing
      intervention as a positive experience. Some also expressed positive regard for
      the research nurse. IMPLICATIONS FOR NURSING: Nurses who are not trained in the
      administration of TT may use quiet time and dialogue to enhance feelings of
      calmness and relaxation in patients with breast cancer.

PMID- 15146229
TI  - Triggers of uncertainty about recurrence and long-term treatment side effects in
      older African American and Caucasian breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To examine the sources of uncertainty in older African
      American and Caucasian long-term breast cancer survivors by focusing on frequency
      of triggers of uncertainty about cancer recurrence and physical symptoms linked
      to long-term treatment side effects. DESIGN: In the context of a larger
      randomized, controlled treatment-outcome study, data were gathered from 10
      monthly follow-up telephone calls by nurses. SETTING: Rural and urban regions of
      North Carolina. SAMPLE: 244 older women (mean age = 64 years); 73 African
      American women and 171 Caucasian women who were five to nine years after breast
      cancer diagnosis. FINDINGS: The most frequent triggers were hearing about someone
      else's cancer and new aches and pains. The most frequent symptoms were fatigue,
      joint stiffness, and pain. Although no ethnic differences occurred in the
      experience of symptoms, Caucasian women were more likely than African American
      women to report that their fears of recurrence were triggered by hearing about
      someone else's cancer, environmental triggers, and information or controversy
      about breast cancer discussed in the media. CONCLUSIONS: Illness uncertainty
      persisted long after cancer diagnosis and treatment, with most women experiencing
      multiple triggers of uncertainty about recurrence and a range of symptoms and
      treatment side effects. IMPLICATIONS FOR NURSING: Nurses can help cancer
      survivors to identify, monitor, and manage illness uncertainty and emotional
      distress.

PMID- 15146230
TI  - Does knowledge influence melanoma-prone behavior? Awareness, exposure, and sun
      protection among five social groups.
AB  - PURPOSE/OBJECTIVES: To examine melanoma-related knowledge, sun exposure, and sun
      protection to determine whether increased awareness is associated with a
      reduction in risk. DESIGN: Quantitative/empiricist study conducted by purpose-
      designed mailed questionnaire. PARTICIPANTS: Consultant oncologists at one
      teaching hospital in London, England; specialist registrars (oncologists in
      training) contacted through a London-based educational group; oncology-trained
      nursing staff from oncology departments at two London teaching hospitals; medical
      students; general (nononcology) nurses; and members of the lay public from one
      London teaching hospital. SETTING: Two teaching hospitals in London, both
      registered cancer centers that possess specialist departments of oncology and are
      staffed by clinical and medical oncologists. METHODS: Anonymous, self-completion,
      mailed questionnaire. RESEARCH VARIABLES: Sun exposure; use of sun protection and
      avoidance; knowledge of the biologic effects of sun exposure, moles, and
      malignant melanoma; melanoma-prone behavior. FINDINGS: No significant differences
      were found in sun exposure or melanoma-prone behavior across the five groups
      studied. No correlation existed between knowledge and melanoma-prone behavior.
      Differences in knowledge and protection scores were demonstrated across all
      groups and were statistically significant, but they did not translate into
      changes in exposure or behavior scores. CONCLUSIONS: Public health policy that
      seeks to reduce the incidence of melanoma is based on the false premise that
      increasing awareness of melanoma risk will reduce melanoma-prone behavior.
      Increasing awareness of the risks of sun exposure may improve the use of sun
      protection, but it does not reduce melanoma-prone behavior, even among specialist
      healthcare professionals. IMPLICATIONS FOR NURSING: This study provides a new
      epidemiologic tool for nurses working in the specialty.

PMID- 15146231
TI  - States step in for stem cell research.

PMID- 15146232
TI  - Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not
      just correlation.
AB  - Antibodies specific for the beta(1)-adrenergic receptor are found in patients
      with chronic heart failure of various etiologies. From work presented in this
      issue of the JCI, we can now infer that these antibodies actually contribute to
      the pathogenesis of chronic heart failure. This commentary discusses mechanisms
      by which these antibodies may engender cardiomyopathy.

PMID- 15146233
TI  - Dissecting the functional role of different isoforms of the L-type Ca2+ channel.
AB  - There currently exist a great number of different mouse lines in which the
      activity of a particular gene of interest has been inactivated or enhanced.
      However, it is also possible to insert specific mutations in a gene so that the
      pharmacological sensitivity of the gene product is altered. An example of such an
      approach shows how the abolition of the sensitivity of an L-type Ca(2+) channel
      isoform to dihydropyridines allows the investigation of the physiological role of
      these channels in different tissues.

PMID- 15146234
TI  - Amyloid at the cutting edge: activation of alpha-secretase prevents
      amyloidogenesis in an Alzheimer disease mouse model.
AB  - The amyloid beta-peptide (A beta peptide) is assumed to play a crucial and early
      role in the pathogenesis of Alzheimer disease. Thus, strategies for a
      pharmacotherapy aim at reducing A beta peptide generation, which proteolytically
      derives from the amyloid precursor protein (APP). The main targets so far have
      been beta- and gamma-secretase, the two proteases that cleave APP at the N- and C
      terminus of the A beta peptide and are thus directly responsible for A beta
      peptide generation. A different strategy, namely the activation of alpha
      secretase, has barely been investigated for its therapeutic potential. alpha
      Secretase cleaves within the A beta peptide domain and thus precludes A beta
      peptide generation. Now, new results demonstrate that activation of alpha
      secretase indeed reduces A beta peptide generation and toxicity in vivo.

PMID- 15146235
TI  - Sepsis: avoiding its deadly toll.
AB  - Systemic bacterial infection may culminate in a frequently fatal septic shock
      syndrome. The underlying pathology is the result of an uncontrolled inflammatory
      response, stimulated by the pathogen and its products. Toll-like receptors (TLRs)
      are critically involved in sensing bacteria and, in the case of sepsis, stimulate
      a pathogenic response by the innate immune system. A new study reports a
      successful attempt to inhibit systemic inflammation in mice by disrupting the
      formation of complexes between Gram-positive bacteria and their cognate receptor,
      TLR2.

PMID- 15146236
TI  - Induction of B7-1 in podocytes is associated with nephrotic syndrome.
AB  - Kidney podocytes and their slit diaphragms form the final barrier to urinary
      protein loss. This explains why podocyte injury is typically associated with
      nephrotic syndrome. The present study uncovered an unanticipated novel role for
      costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular
      permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune
      mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic
      syndrome. The clinical significance of our results is underscored by the
      observation that podocyte expression of B7-1 correlated with the severity of
      human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1
      in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice
      lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link
      between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like
      receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation
      of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm
      proteins. In summary, upregulation of B7-1 in podocytes may contribute to the
      pathogenesis of proteinuria by disrupting the glomerular filter and provides a
      novel molecular target to tackle proteinuric kidney diseases. Our findings
      suggest a novel function for B7-1 in danger signaling by nonimmune cells.

PMID- 15146237
TI  - Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.
AB  - E2F transcription factors are thought to be key regulators of cell growth
      control. Here we use mutant mouse strains to investigate the function of E2F1 and
      E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin
      deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine
      and exocrine cell dysplasia, a reduction in the number and size of acini and
      islets, and their replacement by ductal structures and adipose tissue. Mutant
      pancreatic cells exhibit increased rates of DNA replication but also of
      apoptosis, resulting in severe pancreatic atrophy. The expression of genes
      involved in DNA replication and cell cycle control was upregulated in the
      E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed
      by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant
      pancreas is likely the result of the deregulated expression of these genes.
      Interestingly, the expression of ductal cell and adipocyte differentiation marker
      genes was also upregulated, whereas expression of pancreatic cell marker genes
      were downregulated. These results suggest that E2F1/E2F2 activity negatively
      controls growth of mature pancreatic cells and is necessary for the maintenance
      of differentiated pancreatic phenotypes in the adult.

PMID- 15146238
TI  - Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP
      1c.
AB  - We explored the effects of bile acids on triglyceride (TG) homeostasis using a
      combination of molecular, cellular, and animal models. Cholic acid (CA) prevents
      hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of
      hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of
      SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the
      short heterodimer partner (SHP) and liver X receptor (LXR) alpha and beta, we
      demonstrate the critical dependence of the reduction of SREBP-1c expression by
      either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and
      LXR alpha and LXR beta. These results suggest that strategies aimed at increasing
      FXR activity and the repressive effects of SHP should be explored to correct
      hypertriglyceridemia.

PMID- 15146239
TI  - Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a
      cause of idiopathic dilated cardiomyopathy.
AB  - Today, dilated cardiomyopathy (DCM) represents the main cause of severe heart
      failure and disability in younger adults and thus is a challenge for public
      health. About 30% of DCM cases are genetic in origin; however, the large majority
      of cases are sporadic, and a viral or immune pathogenesis is suspected. Following
      the established postulates for pathogenesis of autoimmune diseases, here we
      provide direct evidence that an autoimmune attack directed against the cardiac
      beta(1)-adrenergic receptor may play a causal role in DCM. First, we immunized
      inbred rats against the second extracellular beta(1)-receptor loop (beta(1)
      EC(II); 100% sequence identity between human and rat) every month. All these rats
      developed first, receptor-stimulating anti-beta(1)-EC(II) Ab's and then, after 9
      months, progressive severe left ventricular dilatation and dysfunction. Second,
      we transferred sera from anti-beta(1)-EC(II)-positive and Ab-negative animals
      every month to healthy rats of the same strain. Strikingly, all anti-beta(1)
      EC(II)-transferred rats also developed a similar cardiomyopathic phenotype within
      a similar time frame, underlining the pathogenic potential of these receptor
      Ab's. As a consequence, beta(1)-adrenergic receptor-targeted autoimmune DCM
      should now be categorized with other known receptor Ab-mediated autoimmune
      diseases, such as Graves disease or myasthenia gravis. Although carried out in an
      experimental animal model, our findings should further encourage the development
      of therapeutic strategies that combat harmful anti-beta(1)-EC(II) in receptor Ab
      positive DCM patients.

PMID- 15146240
TI  - Isoform-specific regulation of mood behavior and pancreatic beta cell and
      cardiovascular function by L-type Ca 2+ channels.
AB  - Ca(v)1.2 and Ca(v)1.3 L-type Ca(2+) channels (LTCCs) are believed to underlie
      Ca(2+) currents in brain, pancreatic beta cells, and the cardiovascular system.
      In the CNS, neuronal LTCCs control excitation-transcription coupling and neuronal
      plasticity. However, the pharmacotherapeutic implications of CNS LTCC modulation
      are difficult to study because LTCC modulators cause cardiovascular (activators
      and blockers) and neurotoxic (activators) effects. We selectively eliminated high
      dihydropyridine (DHP) sensitivity from Ca(v)1.2 alpha 1 subunits (Ca(v)1.2DHP-/-)
      without affecting function and expression. This allowed separation of the DHP
      effects of Ca(v)1.2 from those of Ca(v)1.3 and other LTCCs. DHP effects on
      pancreatic beta cell LTCC currents, insulin secretion, cardiac inotropy, and
      arterial smooth muscle contractility were lost in Ca(v)1.2DHP-/- mice, which
      rules out a direct role of Ca(v)1.3 for these physiological processes. Using
      Ca(v)1.2DHP-/- mice, we established DHPs as mood-modifying agents: LTCC activator
      induced neurotoxicity was abolished and disclosed a depression-like behavioral
      effect without affecting spontaneous locomotor activity. LTCC activator BayK 8644
      (BayK) activated only a specific set of brain areas. In the ventral striatum,
      BayK-induced release of glutamate and 5-HT, but not dopamine and noradrenaline,
      was abolished. This animal model provides a useful tool to elucidate whether
      Ca(v)1.3-selective channel modulation represents a novel pharmacological approach
      to modify CNS function without major peripheral effects.

PMID- 15146241
TI  - Thromboregulatory manifestations in human CD39 transgenic mice and the
      implications for thrombotic disease and transplantation.
AB  - Extracellular nucleotides play an important role in thrombosis and inflammation,
      triggering a range of effects such as platelet activation and recruitment,
      endothelial cell activation, and vasoconstriction. CD39, the major vascular
      nucleoside triphosphate diphosphohydrolase (NTPDase), converts ATP and ADP to
      AMP, which is further degraded to the antithrombotic and anti-inflammatory
      mediator adenosine. Deletion of CD39 renders mice exquisitely sensitive to
      vascular injury, and CD39-null cardiac xenografts show reduced survival.
      Conversely, upregulation of CD39 by somatic gene transfer or administration of
      soluble NTPDases has major benefits in models of transplantation and
      inflammation. In this study we examined the consequences of transgenic expression
      of human CD39 (hCD39) in mice. Importantly, these mice displayed no overt
      spontaneous bleeding tendency under normal circumstances. The hCD39 transgenic
      mice did, however, exhibit impaired platelet aggregation, prolonged bleeding
      times, and resistance to systemic thromboembolism. Donor hearts transgenic for
      hCD39 were substantially protected from thrombosis and survived longer in a mouse
      cardiac transplant model of vascular rejection. These thromboregulatory
      manifestations in hCD39 transgenic mice suggest important therapeutic potential
      in clinical vascular disease and in the control of serious thrombotic events that
      compromise the survival of porcine xenografts in primates.

PMID- 15146242
TI  - Cortical spreading depression activates and upregulates MMP-9.
AB  - Cortical spreading depression (CSD) is a propagating wave of neuronal and glial
      depolarization and has been implicated in disorders of neurovascular regulation
      such as stroke, head trauma, and migraine. In this study, we found that CSD
      alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning
      at 3-6 hours, MMP-9 levels increased within cortex ipsilateral to the CSD,
      reaching a maximum at 24 hours and persisting for at least 48 hours.
      Gelatinolytic activity was detected earliest within the matrix of cortical blood
      vessels and later within neurons and pia arachnoid (> or =3 hours), particularly
      within piriform cortex; this activity was suppressed by injection of the
      metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator
      (1,10-phenanthroline). At 3-24 hours, immunoreactive laminin, endothelial barrier
      antigen, and zona occludens-1 diminished in the ipsilateral cortex, suggesting
      that CSD altered proteins critical to the integrity of the BBB. At 3 hours after
      CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin
      leakage was suppressed by the administration of GM6001. Protein leakage was not
      detected in MMP-9-null mice, implicating the MMP-9 isoform in barrier disruption.
      We conclude that intense neuronal and glial depolarization initiates a cascade
      that disrupts the BBB via an MMP-9-dependent mechanism.

PMID- 15146244
TI  - Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters
      orally exposed to scrapie.
AB  - Recently, pathological prion protein PrP(Sc), the putative key constituent of
      infectious agents causing transmissible spongiform encephalopathies (TSEs), was
      found in muscles of rodents experimentally infected with scrapie and in patients
      with Creutzfeldt-Jakob disease (CJD). For the assessment of risk scenarios
      originating from these findings (e.g., alimentary transmission of pathogens
      associated with bovine spongiform encephalopathy [BSE] and chronic wasting
      disease [CWD] via tainted beef and game or iatrogenic dissemination of CJD agent
      through contaminated surgical instruments) more detailed information about the
      time course of PrP(Sc) accumulation in muscles at preclinical and clinical stages
      of incubation is needed. Here we show that PrP(Sc) in muscles of hamsters fed
      with scrapie can be detected prior to the onset of clinical symptoms, but that
      the bulk of PrP(Sc) was deposited late in clinical disease. Additionally,
      regarding the question of how muscles become invaded, we report on the
      intramuscular location of PrP(Sc) and substantial indications for centrifugal
      spread of infection from spinal motor neurons to myofibers. Our findings in a
      well-established animal model for TSEs contribute to a better assessment of the
      risks for public health emanating from "Prions in skeletal muscle" and provide
      new insights into the pathophysiological spread of TSE agents through the body.

PMID- 15146243
TI  - A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal
      defects in an Alzheimer disease mouse model.
AB  - Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta
      peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the
      amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A
      beta peptide sequence. Proteinases of the ADAM family (adisintegrin and
      metalloproteinase) are the main candidates as physiologically relevant alpha
      secretases, but early lethality of knockout animals prevented a detailed analysis
      in neuronal cells. To overcome this restriction, we have generated transgenic
      mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In
      this report we show that a moderate neuronal overexpression of ADAM10 in mice
      transgenic for human APP([V717I]) increased the secretion of the neurotrophic
      soluble alpha-secretase-released N-terminal APP domain (APPs alpha), reduced the
      formation of A beta peptides, and prevented their deposition in plaques.
      Functionally, impaired long-term potentiation and cognitive deficits were
      alleviated. Expression of mutant catalytically inactive ADAM10 led to an
      enhancement of the number and size of amyloid plaques in the brains of double
      transgenic mice. The results provide the first in vivo evidence for a proteinase
      of the ADAM family as an alpha-secretase of APP, reveal activation of ADAM10 as a
      promising therapeutic target, and support the hypothesis that a decrease in alpha
      secretase activity contributes to the development of AD.

PMID- 15146245
TI  - Antagonistic antibody prevents toll-like receptor 2-driven lethal shock-like
      syndromes.
AB  - Hyperactivation of immune cells by bacterial products through toll-like receptors
      (TLRs) is thought of as a causative mechanism of septic shock pathology.
      Infections with Gram-negative or Gram-positive bacteria provide TLR2-specific
      agonists and are the major cause of severe sepsis. In order to intervene in TLR2
      driven toxemia, we raised mAb's against the extracellular domain of TLR2. Surface
      plasmon resonance analysis showed direct and specific interaction of TLR2 and
      immunostimulatory lipopeptide, which was blocked by T2.5 in a dose-dependent
      manner. Application of mAb T2.5 inhibited cell activation in experimental murine
      models of infection. T2.5 also antagonized TLR2-specific activation of primary
      human macrophages. TLR2 surface expression by murine macrophages was surprisingly
      weak, while both intra- and extracellular expression increased upon systemic
      microbial challenge. Systemic application of T2.5 upon lipopeptide challenge
      inhibited release of inflammatory mediators such as TNF-alpha and prevented
      lethal shock-like syndrome in mice. Twenty milligrams per kilogram of T2.5 was
      sufficient to protect mice, and administration of 40 mg/kg of T2.5 was protective
      even 3 hours after the start of otherwise lethal challenge with Bacillus
      subtilis. These results indicate that epitope-specific binding of exogenous
      ligands precedes specific TLR signaling and suggest therapeutic application of a
      neutralizing anti-TLR2 antibody in acute infection.

PMID- 15146246
TI  - TLR2 is mobilized into an apical lipid raft receptor complex to signal infection
      in airway epithelial cells.
AB  - Toll-like receptors (TLRs) mediate host responses to bacterial gene products. As
      the airway epithelium is potentially exposed to many diverse inhaled bacteria,
      TLRs involved in defense of the airways must be broadly responsive, available at
      the exposed apical surface of the cells, and highly regulated to prevent
      activation following trivial encounters with bacteria. We demonstrate that TLR2
      is enriched in caveolin-1-associated lipid raft microdomains presented on the
      apical surface of airway epithelial cells after bacterial infection. These
      receptor complexes include myeloid differentiation protein (MyD88), interleukin-1
      receptor-activated kinase-1, and TNF receptor-associated factor 6. The signaling
      capabilities of TLR2 are amplified through its association with the
      asialoganglioside gangliotetraosylceramide (Gal beta 1,2GalNAc beta 1,4Gal beta
      1,4Glc beta 1,1Cer), which has receptor function itself for many pulmonary
      pathogens. Ligation of either TLR2 or asialoGM1 by ligands with specificity for
      either receptor, by Pseudomonas aeruginosa, or by Staphylococcus aureus
      stimulates IL-8 production through activation of NF-kappa B, as mediated by TLR2
      and MyD88. Thus, TLR2 in association with asialo-glycolipids presented within the
      context of lipid rafts provides a broadly responsive signaling complex at the
      apical surfaces of airway cells to initiate the host response to potential
      bacterial infection.

PMID- 15146250
TI  - [Editorial].

PMID- 15146251
TI  - [In Process Citation].

PMID- 15146247
TI  - Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an
      atypical Th2 response in ulcerative colitis.
AB  - While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the
      immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative
      colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells
      from UC patients produce significantly greater amounts of IL-13 (and IL-5) than
      control cells and little IFN-gamma, whereas comparable cells from CD patients
      produce large amounts of IFN-gamma and small amounts of IL-13. We then show that
      stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/anti-CD28
      or with B cells expressing transfected CD1d induces substantial IL-13 production.
      While this provided firm evidence that the IL-13-producing cell is an NK T (NKT)
      cell, it became clear that this cell does not express invariant NKT cell
      receptors characteristic of most NKT cells since there was no increase in cells
      binding alpha-galactosylceramide-loaded tetramers, and alpha-galactosylceramide
      did not induce IL-13 secretion. Finally, we show that both human NKT cell lines
      as well as UC CD161(+) LPT cells are cytotoxic for HT-29 epithelial cells and
      that this cytotoxicity is augmented by IL-13. These studies show that UC is
      associated with an atypical Th2 response mediated by nonclassical NKT cells
      producing IL-13 and having cytotoxic potential for epithelial cells.

PMID- 15146252
TI  - [Cardiac Surgery in very high-risk patients].
AB  - PURPOSE: To assess the results obtained in very high-risk patients, which are
      those patients with an EUROSCORE greater than 13 points. MATERIAL AND METHODS:
      From September 2001 to September 2003, thirty-three very high-risk patients were
      operated on in our department, which represents 1.6% of all the surgical activity
      during that period of time, being 17 male and 16 female, with an average of 69
      years old (maximum 86 and minimum 32). Diagnosis includes: post infarction CIV 5,
      coronary insufficiency 11, aortic dissection 3, mitral prosthesis 3, valvular
      disease 9, aortic prosthesis disfunction 2. Fifteen patients underwent an
      emergency procedure, 12 were urgent and the remaining 6 were electively operated
      on. RESULTS: Overall post-operative mortality was 12 patients (36%), being 6
      emergent, 5 urgent and 1 elective patient. Patients who survived the operation
      had longer intensive care and hospital admission periods, which will be analyzed
      in detail. CONCLUSION: Surgery can be justified in very high risk patients.
      Despite the high perioperative mortality and longer periods of hospital stay,
      they will be otherwise condamned to death, if surgery would not be performed.

PMID- 15146248
TI  - Autologous lymphoma vaccines induce human T cell responses against multiple,
      unique epitopes.
AB  - The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a
      tumor-specific antigen and an attractive target for active immunotherapy. While
      Ab's specific for tumor idiotype have been well described in patients with B cell
      malignancies, the precise antigenic epitopes in human idiotype recognized by
      autologous T cells remain largely unknown. We report here that T cell lines
      generated from lymphoma patients actively immunized with idiotype protein
      specifically recognized multiple, unique immunodominant epitopes in autologous
      tumor idiotype. Synthetic peptides corresponding to hypervariable, but not
      framework, regions of Ig heavy chain specifically stimulated CD4(+) and CD8(+) T
      cells to proliferate and secrete proinflammatory cytokines in an MHC-associated
      manner. Detailed analysis revealed a minimal determinant of an immunodominant
      epitope, comprising critical residues at the amino terminus that may be a product
      of somatic hypermutation. Association of idiotype-specific T cell responses with
      previously documented molecular remissions in idiotype-vaccinated patients
      suggests that the newly identified T cell epitopes may be clinically relevant.
      Such antigenic epitopes may serve as candidates for novel peptide-vaccine
      strategies, and as tools to selectively expand tumor antigen-specific T cells for
      adoptive immunotherapy and for monitoring T cell immunity in vaccinated patients.

PMID- 15146253
TI  - [Initial results on the use of mechanical devices for proximal saphenous vein
      graft anastomoses: a clinical and angiographic evaluation].
AB  - OBJECTIVE: To report on our initial clinical experience of the utilization of a
      mechanical anastomotic device (MAD) to perform saphenous vein graft to aorta
      anastomosis. METHOD: Between June 2002 and May 2003, 17 patients, including 13
      male, with a mean age of 64.4 +/- 9.4 years, were selected for coronary artery
      bypass grafting using MAD. A total of 49 anastomoses, 19 arterial and 30 vein
      grafts, were performed with a mean of 2.9 +/-0.5 anastomoses per patient. Eleven
      (36.7%) vein-graft anastomoses were performed with conventional sutures and 19
      (63.3%) using MAD. The clinical evolution, enzymatic and electrocardiographic
      alterations as well as an angiographic study were analyzed in the postoperative
      period. RESULTS: Of the 17 patients, the mechanical device was used on 16
      (94.1%). Six (37.5%) patients were operated on under cardiopulmonary bypass with
      a mean time of 102.9 +/-16.9 minutes. The postoperative evolution was
      satisfactory in all patients. No patient presented with enzymatic, myocardial
      infarction or other ischemic electrocardiographic alterations in the immediate
      postoperative period. Early postoperative angiography was performed in 9 (52.9%)
      patients. The anastomoses of the left internal thoracic artery to left anterior
      descending artery were patent in all cases. Of the 15 saphenous vein grafts
      studied, 11 (73.3%) were performed using MAD, 9 (81.8%) of which were patent. All
      the 4 conventionally sutured vein anastomoses were patent. No hospital deaths
      occurred. In the late follow-up, 88.2% of the patients were free of cardiac
      related events. CONCLUSIONS: MAD for vein graft-to-aorta anastomoses proved to be
      feasible, but a wider analysis of the benefits of its utilization regarding
      operative time, aggression to the patient, patency of the grafts and final cost
      are necessary.

PMID- 15146254
TI  - Importance of extrasegmental vessels for spinal cord blood supply in a chronic
      porcine model.
AB  - IObjective: Our purpose was to investigate the interaction of the important
      components of spinal cord blood supply in the pig model to enable its use for
      future studies of spinal cord protection. METHODS: 25 juvenile pigs (20-22 Kg)
      underwent serial intercostal (IC) or lumbar artery (LA) ligation until
      disappearance of motor evoked potentials (MEPs). Pigs underwent sequential
      craniocaudal (IC/LA ligation alone (n=5); following clamping of both subclavian
      arteries (n=4)m, or clamping of the median sacral artery (MSA, n=4); preceded by
      clamping of the subclavian arteries (n=4), or of the MSA (n=4). RESULTS were
      verified by Tarlov's scores and perioperative angiography. RESULTS: All animals
      with MEP loss suffered postoperative paraplegia. Groups were equivalent with
      regard to stable arterial pressures throughout the experiment, temperature and
      other physiological parameters. Mean number of clamped IC/LA before MEP loss for
      cranio-caudal clamping direction was 12.8 +/-0.8 for segmental arteries isolated,
      9 +/-0.8 if both subclavian arteries were ligated previously and only 4.3 +/- 0.5
      IC if the median sacral artery was clamped before. Mean number of clamped LA for
      caudo-cranial clamping direction was 5.8 +/-0.9 for segmental lumbar arteries,
      5.5 +/-0.6 LA if both subclavian arteries were ligated previously and 3.5 +/-0.6
      if the median sacral artery was clamped before. CONCLUSION: This study confirms
      the importance of lumbar and MSA arteries to cord viability. It documents the
      interaction of the subclavian and MSA (roughly equivalent to the hypogastric
      arteries in humans) with segmental vessels in providing spinal cord blood supply.
      It also provides the physiologic basis for use of the pig model for studies of
      spinal cord protection in aortic surgery.

PMID- 15146255
TI  - [Penetrating ulcers of the descending thoracic aorta: Diagnosis and surgical
      management].
AB  - In this paper two patients with penetrating ulcers of the descending thoracic
      aorta are presented, a clinical condition recognized only recently, that may have
      a severe or even fatal outcome, due to rupture of the aorta. It is a peculiar
      form of the atherosclerotic disease, and its clinical and imagiologic
      presentation may mimics the classic aortic dissection of the distal type type.
      Computed tomography, nuclear magnetic resonance and transesophageal
      ecocardiography are the most apropriate methods for studying and diagnosis and
      the surgical management, aimed at the prevention or treatment of the aortic
      rupture, and based on the prosthetic aortic replacement, is the only alternative
      allowing the definite cure of the disease. The main features of pathology,
      clinical manifestations, diferential diagnosis and surgical management of this
      entity are described and discussed, according to the most recently articles
      published in the literature, on the subject.

PMID- 15146256
TI  - [Popliteal artery entrapment syndrome].
AB  - The popliteal artery entrapment syndrome is characterized by extrinsic
      compression of this artery as a result of anatomic deviation from its usual
      course, or by compression from musculotendinous structures in the popliteal
      fossa. Clinical symptoms appear when these affected individuals do strenuous
      exercises. There are two types of popliteal artery entrapment syndrome: the
      classicalor congenital form, and the functional or acquired form. In the
      classical form, disturbances in the embryogenesis lead either directy to
      popliteal artery anomalies or to alterations of adjacent structures that cause
      compression of the popliteal artery. In the functional form, hypertrophy of the
      gastrocnemius muscle secondary to exercise has been postulated as a cause. In
      both types, diagnosis is made through the detection of total occlusion or
      important stenosis of the popliteal artery. This is identified by duplex scan,
      magnetic resonance or arteriography during active plantar flexion-extension. A
      positive test in non-symptomatic subjects presenting no anatomical anomalies led
      to discussions about its specificity. This study presents a review of anatomical
      and functional popliteal artery entrapment syndrome and discusses accuracy,
      sensitivity and specificity of the diagnostic tests.

PMID- 15146259
TI  - [In Process Citation].

PMID- 15146257
TI  - ["Ex-vivo" renal artery revascularization].
AB  - Three patients with renovascular hypertension due to complex and branch lesions
      of the renal artery are reported, successfully managed by a technique consisting
      in the "ex-vivo" repair of the lesions followed by kidney autotransplantation.
      The indications and technical details of the procedure are subjected to a
      description and discussion.

PMID- 15146258
TI  - [Vascular surgery and transplantation].
AB  - As Honorary President of the Joint Meeting of Portuguese Society for
      Cardiothoracic and Vascular Surgery and the Portuguese Society of
      Transplantation, the author addressed a conference in which he emphasized the
      straigth links existing between Vascular Surgery and Organ Transplantation
      Surgery, and describes his professional course and the historical development of
      transplantation in its Department and Hospital, as well as in the remaining
      country, an area in which he was proeminent protagonist and pionner, leading to
      his nomination to distinguished functions of National Coordinator of Organ
      Transplantation in Portugal.

PMID- 15146260
TI  - Intravenous immunoglobulin: use in dermatology.
AB  - A manufactured blood product derived from fractionated human plasma, intravenous
      immunoglobulin (i.v.Ig) contains supra-physiologic levels of IgG. i.v.Ig is
      currently used in the treatment of immunodeficiency syndromes, inflammatory
      disorders and infections diseases. Uncontrolled clinical studies and anecdotal
      case reports recommend its use in dermatology, but randomized clinical trials are
      lacking. In selecting the most appropriate i.v.Ig for the patient, convenience,
      efficacy, safety and tolerability of the different products should be considered.
      With several measures in place to ensure its safety, i.v.Ig offers new hope for
      the treatment of many severe dermatologic conditions.

PMID- 15146261
TI  - New approaches to surgery of lentigo maligna.
AB  - Lentigo maligna (LM) is a pigmented lesion that occurs most commonly on the sun
      exposed skin of the head and neck of an older patient. LM can be difficult to
      completely remove due to its occasional extensive subclinical extension. Surgical
      treatments, including standard excision and margin-controlled excision (Mohs
      micrographic surgery or rush permanent sections), are reviewed. Immunostains that
      can increase sensitivity and specificity of margin-controlled excision are
      discussed, and other nonscalpel treatments including destruction, topical
      imiquimod, radiation therapy and cryotherapy are briefly discussed. The gold
      standard treatment for LM is margin-controlled excision.

PMID- 15146262
TI  - Tazarotene 0.1% cream for the treatment of photodamage.
AB  - Tazarotene (Tazorac, Allergan) has been shown to be effective in reducing the
      effects of photoaging in short term studies. To determine its effectiveness in
      the longer term, a 24-week multicenter, double-blind, randomized, vehicle
      controlled intervention study of 562 patients with facial photodamage was carried
      out followed by a 28-week open label extension. Patients were treated with one
      daily application of tazarotene 0.1% cream or vehicle cream to the face for 24
      weeks, then tazarotene 0.1% cream for another 28 weeks. At week 24, when compared
      to vehicle, tazarotene resulted in a significantly greater incidence of patients
      achieving treatment success (over 50 percent greater improvement) and at least a
      1 grade improvement in fine wrinkling, mottled pigmentation, pore size,
      lentigines, elastosis, irregular depigmentation, tactile roughness, coarse
      wrinkling and overall integrated assessment of photodamage. Additional clinical
      improvement occurred with continued tazarotene treatment and had not plateaued by
      week 52.

PMID- 15146263
TI  - Drug treatments for skin disease introduced in 2003.

PMID- 15146264
TI  - Squamous cell carcinoma in organ transplant recipients: approach to management.
AB  - Skin cancer, particularly squamous cell carcinoma (SCC), continues to be a
      significant cause of morbidity and even mortality in organ transplant recipients
      (OTRs). As the number of organ transplant patients continues to increase,
      dermatologists will be faced with the challenge of diagnosing and managing their
      skin cancers. Evaluation, management and follow up of organ transplant recipients
      with high risk SCC will be discussed.

PMID- 15146266
TI  - A butterfly's chemical key to various ant forts: intersection-odour or aggregate
      odour multi-host mimicry?
AB  - Deception is a crucial yet incompletely understood strategy of social parasites.
      In central Europe, the Mountain Alcon Blue, Maculinea rebeli, a highly endangered
      butterfly, parasitises several Myrmica ant species. Caterpillars gain access to
      host nests probably by faking the ants' odour. We analysed gas chromatography
      mass spectrometry data of body surface hydrocarbons of pre-adoption and
      hibernated larvae of Maculinea rebeli and of their host species Myrmica sabuleti
      and M. schencki. Data were ordinated by different methods, based on similarities
      in the relative quantities of compounds between chromatograms. The two Myrmica
      species exhibit species-specific profiles. The Maculinea rebeli pre-adoption
      larva has a complex profile that simultaneously contains species-specific
      substances of the two investigated host species. This evidence leads to the
      interpretation that, in central Europe, Maculinea rebeli is predisposed for multi
      host use by the chemical signature of its pre-adoption larva. The Maculinea
      rebeli larva clearly does not rely on an "intersection-odour" of compounds common
      to all host ant species, but synthesises an "aggregate-odour" containing specific
      compounds of each of the investigated hosts. We term this previously unknown
      chemical strategy "aggregate-odour multi-host mimicry".

PMID- 15146265
TI  - In search of the sky compass in the insect brain.
AB  - Like many vertebrate species, insects rely on a sun compass for spatial
      orientation and long- range navigation. In addition to the sun, however, insects
      can also use the polarization pattern of the sky as a reference for estimating
      navigational directions. Recent analysis of polarization vision pathways in the
      brain of orthopteroid insects sheds some light onto brain areas that might act as
      internal navigation centers. Here I review the significance, peripheral
      mechanisms, and central processing stages for polarization vision in insects with
      special reference to the locust Schistocerca gregaria. As in other insect
      species, polarization vision in locusts relies on specialized photoreceptor cells
      in a small dorsal rim area of the compound eye. Stages in the brain involved in
      polarized light signaling include specific areas in the lamina, medulla and
      lobula of the optic lobe and, in the midbrain, the anterior optic tubercle, the
      lateral accessory lobe, and the central complex. Integration of polarized-light
      signals with information on solar position appears to start in the optic lobe. In
      the central complex, polarization-opponent interneurons form a network of
      interconnected neurons. The organization of the central complex, its connections
      to thoracic motor centers, and its involvement in the spatial control of
      locomotion strongly suggest that it serves as a spatial organizer within the
      insect brain, including the functions of compass orientation and path
      integration. Time compensation in compass orientation is possibly achieved
      through a neural pathway from the internal circadian clock in the accessory
      medulla to the protocerebral bridge of the central complex.

PMID- 15146268
TI  - The function of dart behavior in the paper wasp, Polistes fuscatus.
AB  - Dominance behavior in Polistes wasps is a composite trait consisting of various
      discrete behaviors such as darts, lunges, bites, and mounts. The majority of
      these behaviors are considered "aggressive", and these aggressive behaviors are
      considered to form a continuum from mild (e.g., darts) to severe (e.g., falling
      fights). In this paper we focus on darts, the most common of the dominance
      behaviors, and investigate their function in un-manipulated post-emergent
      colonies of the primitively eusocial wasp P. fuscatus. Here we show that darts
      are correlated with the more severe dominance behaviors, and that dominance ranks
      do not change with the addition or exclusion of darts. We find no correlation,
      however, between receiving darts and receiving more severe dominance behaviors.
      This result suggests that darts are not indicative of aggressive reinforcement of
      dominance, but rather may serve a different function. Our data suggest that the
      function of darts is to regulate activity on nests. Both foundresses and workers
      dart inactive workers significantly more often than by chance, and workers
      respond to a foundress's (but not a worker's) dart by becoming less inactive. We
      also found that active workers who receive a dart from either a foundress or
      worker respond mostly by switching from one activity to another. Thus, our data
      suggest that darts are not aggressive behaviors, that foundresses use this signal
      to initiate activity, and that foundresses and workers both use the signal to
      regulate worker activity.

PMID- 15146267
TI  - Avoidance of nonhost plants by a bark beetle, Pityogenes bidentatus, in a forest
      of odors.
AB  - The bark beetle, Pityogenes bidentatus (Coleoptera: Scolytidae), searches in
      mixed conifer and deciduous forests of northern Europe for suitable branches of
      its host, Scots pine ( Pinus sylvestris). We tested whether odors from several
      diverse nonhost trees and plants common in the habitat (e.g., mountain ash,
      Sorbus aucuparia; oak, Quercus robur; alder buckthorn, Frangula alnus; blueberry,
      Vaccinium myrtillus; raspberry, Rubus idaeus; and grass, Deschampsia flexuosa)
      would reduce the attraction of the bark beetle to traps releasing its aggregation
      pheromone components in the field. Volatiles from the leaves or bark of each of
      these plants significantly reduced the attraction of the beetles to their
      pheromone. Odors collected from these nonhosts and analyzed by GC/MS contained
      monoterpenes, sesquiterpenes, and "green-leaf" alcohols, several of which (e.g.,
      1-octene-3-ol and beta-caryophyllene) reduced the attraction to pheromone in the
      field and elicited electroantennographic responses. In the laboratory,
      reproduction by the beetle was marginal in nonhost Norway spruce, Picea abies,
      and was absent in the other nonhost trees. Olfactory avoidance of unsuitable
      nonhosts may have evolved due to advantages in avoiding mistakes during host
      selection.

PMID- 15146269
TI  - Fine colour discrimination requires differential conditioning in bumblebees.
AB  - Accurate recognition requires that visual systems must be able to discriminate
      between target and distractor stimuli. Flowers are learned and recognised by bees
      using visual cues including colour and shape. We investigated whether bees were
      able to learn to discriminate between colours differently depending upon absolute
      or differential conditioning. For absolute conditioning bees were rewarded with
      sucrose solution for visits to target flowers. When distractor stimuli were
      subsequently presented, a high level of discrimination was observed if there was
      a perceptually large colour distance separating distractors and targets, but for
      a perceptually small colour distance the bees generalised and did not
      discriminate between stimuli. When provided with differential conditioning where
      both target and distractors were present, the bees learnt to discriminate stimuli
      separated by a perceptually small colour distance. This shows that for bees to
      learn fine colour discrimination tasks it is important to use differential
      conditioning. The findings are discussed within the context of the necessity for
      plants to produce distinctive flower colours.

PMID- 15146270
TI  - Conditioning procedure and color discrimination in the honeybee Apis mellifera.
AB  - We studied the influence of the conditioning procedure on color discrimination by
      free-flying honeybees. We asked whether absolute and differential conditioning
      result in different discrimination capabilities for the same pairs of colored
      targets. In absolute conditioning, bees were rewarded on a single color; in
      differential conditioning, bees were rewarded on the same color but an
      alternative, non-rewarding, similar color was also visible. In both conditioning
      procedures, bees learned their respective task and could also discriminate the
      training stimulus from a novel stimulus that was perceptually different from the
      trained one. Discrimination between perceptually closer stimuli was possible
      after differential conditioning but not after absolute conditioning. Differences
      in attention inculcated by these training procedures may underlie the different
      discrimination performances of the bees.

PMID- 15146271
TI  - Conservation of Bio synthetic pheromone pathways in honeybees Apis.
AB  - Social insects use complex chemical communication systems to govern many aspects
      of their life. We studied chemical changes in Dufour's gland secretions
      associated with ovary development in several genotypes of honeybees. We found
      that C28-C38 esters were associated only with cavity nesting honeybee queens,
      while the alcohol eicosenol was associated only with their non-laying workers. In
      contrast, both egg-laying anarchistic workers and all parasitic Cape workers from
      queenright colonies showed the typical queen pattern (i.e. esters present and
      eicosenol absent), while egg-laying wild-type and anarchistic workers in
      queenless colonies showed an intermediate pattern, producing both esters and
      eicosenol but at intermediate levels. Furthermore, neither esters nor eicosenol
      were found in aerial nesting honeybee species. Both esters and eicosenol are
      biosynthetically similar compounds since both are recognizable products of fatty
      acid biosynthesis. Therefore, we propose that in honeybees the biosynthesis of
      esters and eicosenol in the Dufour's gland is caste-regulated and this pathway
      has been conserved over evolutionary time.

PMID- 15146272
TI  - Collective decision through self-assembling.
AB  - The ant genus Oecophylla is well known for forming chains that allow a gap to be
      bridged. Using a set-up where the ants are given the choice of building a chain
      on two identical sites, we show that they always end up focusing their activity
      on a single one. A mathematical model suggests that this result depends on
      probabilities of entering and leaving the chain that depend on its size. The same
      model allows some predictions to be made on the influence of the nest size. Thus,
      a critical population size is needed in order to observe the formation of at
      least one chain. Over this size we observe the transitory coexistence of two
      chains, for which the duration is positively correlated to the nest size.
      However, this coexistence always leads to the formation of one chain and to the
      break-up of the other one. Following on from these results we give similar
      examples in gregarious arthropods and discuss the possibility of these mechanisms
      being generic for a wide range of collective activities and decisions.

PMID- 15146273
TI  - Impairment of male reproduction in adult rats exposed to hydroxyprogesterone
      caproate in utero.
AB  - Hydroxyprogesterone caproate is one of the most effective and widely used drugs
      for the treatment of uterine bleeding and threatened miscarriage in women.
      Hydroxyprogesterone caproate was administered to pregnant rats in order to assess
      the effect of intraperitoneal exposure to supranormal levels of
      hydroxyprogesterone caproate on the male reproductive potential in the first
      generation. The cauda epididymal sperm count and motility decreased significantly
      in rats exposed to hydroxyprogesterone caproate during embryonic development,
      when compared with control rats. The levels of serum testosterone decreased with
      an increase in follicle stimulating hormone and luteinizing hormone in adult rats
      exposed to hydroxyprogesterone caproate during the embryonic stage. It was
      suggested that the impairment of male reproductive performance could be mediated
      through the inhibition of testosterone production.

PMID- 15146274
TI  - Web-building spiders attract prey by storing decaying matter.
AB  - The orb-weaving spider Nephila edulis incorporates into its web a band of
      decaying animal and plant matter. While earlier studies demonstrate that larger
      spiders utilise these debris bands as caches of food, the presence of plant
      matter suggests additional functions. When organic and plastic items were placed
      in the webs of N. edulis, some of the former but none of the latter were
      incorporated into the debris band. Using an Y-maze olfactometer, we show that
      sheep blowflies Lucilia cuprina are attracted to recently collected debris bands,
      but that this attraction does not persist over time. These data reveal an
      entirely novel foraging strategy, in which a sit-and-wait predator attracts
      insect prey by utilising the odours of decaying organic material. The spider's
      habit of replenishing the debris band may be necessary to maintain its efficacy
      for attracting prey.

PMID- 15146275
TI  - [Current diving medicine. 1. The Heidelberg Symposium on Diving Medicine, 22
      November 2003].

PMID- 15146276
TI  - [Terbinafine-induced subacute cutaneous lupus erythematosus. Case report and
      review of the literature].
AB  - We report on a patient with terbinafine-induced SCLE covering clinical,
      histopathological and serological findings. Positive serological results included
      ANA, SS-A (Ro)-antibodies and anti-histone-antibodies with specificity for H1 and
      H3. The literature on terbinafine-induced SCLE is reviewed. We discuss H1- and H3
      specific anti-histone antibodies as a possible diagnostic criterion of drug
      induced SCLE.

PMID- 15146277
TI  - [Quality management during postoperative pain therapy].
AB  - BACKGROUND: A main target of surgical treatment is to minimize postoperative
      pain. The aim of this study was to evaluate the benefit of quality management on
      postoperative pain and to improve pain therapy. METHODS: In a prospective study,
      postoperative pain was recorded in a total of 700 patients in a general and
      visceral surgical ward in 2000, 2001, and 2002. Pain was measured on a ten-point
      visual analogue scale (0 no pain, 10 most severe pain). RESULTS: Applying the
      principles of quality management (plan, do, check, act), we analyzed the reasons
      for high pain scores in detail. After study of the results in 2000, additional
      recommendations and guidelines for perioperative pain therapy were provided to
      all the physicians, and the mean visual analogue pain scores decreased by 15% in
      2001 and more than 30% in 2002. At baseline, 12% of patients had pain above the
      threshold of 3 at rest and 5 in motion. These scores could be reduced to 6% and
      3% in the two successive years, respectively. CONCLUSION: A simple pain
      management system in a general surgical ward led to considerable improvement in
      postoperative pain scores as assessed by visual analogue scale.

PMID- 15146278
TI  - [Not all vocal cord failure following thyroid surgery is recurrent paresis due to
      damage during operation. Statement of the German Interdisciplinary Study Group on
      Intraoperative Neuromonitoring of Thyroid Surgery concerning recurring paresis
      due to intubation].
AB  - Since the phoniatrician H. Bauer described the first case of recurrent laryngeal
      nerve palsy most likely caused by intubation some 45 years ago, several case
      reports have been published. However, systematic analyses regarding the frequency
      of recurrent laryngeal nerve palsies due to intubation are scarce, and none of
      them has used the proper methods to demonstrate clearly that such a mechanism
      exists. Currently available data justify the assumption that not every recurrent
      laryngeal nerve palsy following thyroid surgery is due to the operation itself
      and that the damage caused by intubation, however, may only account for a
      minority of these cases. The differential diagnosis of postoperative recurrent
      laryngeal nerve palsy requires the use of specific tools which go beyond simple
      laryngoscopy and include stroboscopy as well as intra- and extralaryngeal
      electromyography. A partial palsy of recurrent laryngeal nerve due to intubation
      would be associated with severe dysphonia or aphonia, not with dyspnea because of
      the typical intermediate position of the paralyzed vocal folds with a normal
      electromyographic function of the cricothyroid muscle. The use of these methods
      to identify the nature of postoperative recurrent laryngeal nerve palsy is
      recommended in cases of regular intraoperative neuromonitoring but
      postoperatively impaired function of the vocal cords.

PMID- 15146280
TI  - [Indications for treating stenoses of the carotid artery].
AB  - The annual stroke risk for patients with asymptomatic stenoses of the carotid
      artery is around 1% in case of <70% stenosis (NASCET criteria) and 2-5% in
      patients with >70% stenosis. The risk of recurrent ischemic events for patients
      with symptomatic stenoses is much higher, around 15% during the first year. For
      more than 10 years, the efficacy of carotid surgery has been proven, and there is
      growing evidence to support surgery in case of asymptomatic stenosis. Patients
      with severe stenoses, male or elderly patients, and those with bilateral stenoses
      benefit more from surgery. Carotid artery stenting has not proven its safety or
      efficacy. Despite this lack of evidence, the method is used in many centers as an
      alternative to surgery. Especially symptomatic carotid artery stenosis should be
      used mainly in the setting of a randomized trial such as SPACE.

PMID- 15146282
TI  - [Sinus vein thrombosis. A rare complication of heparin-induced thrombocytopenia
      type II].
AB  - In the past 10 years numerous reports of cases referring to complications and
      their outcome with heparin-induced thrombocytopenia type II (HIT II) have been
      published. Clinically these symptoms are manifested as a combination of arterial
      and venous thromboembolisms. Mostly affected are the vessels of the limbs, the
      abdomen, kidneys and coronary arteries. We present the most rare initial
      manifestations of cerebral symptoms with headache, nausea, change of character
      and generalised convulsion, which have found their origin in sinus vein
      thrombosis and the treatment with the heparinoid danaparoid.

PMID- 15146283
TI  - [Inadvertent intravenous infusion of 380 mg ropivacaine].
AB  - This is a report about an inadvertent intravenous infusion of 380 mg ropivacaine
      in a 84-year-old patient over a period of 1.75 h. The level of serum ropivacaine
      measured immediately after the end of the infusion as well as 2 h and 7 h later,
      was initially in the lower toxic range (free concentration of 0.48 micro g/ml).
      The patient showed no symptoms of intoxication neither clinically nor during the
      technical examinations (EEG, ECG). This case confirms the wide therapeutic range
      of ropivacaine.

PMID- 15146281
TI  - [Biodegradable cage. Osteointegration in spondylodesis of the sheep cervical
      spine].
AB  - Bioabsorbable implants are commonplace in knee and shoulder surgery.
      Bioabsorbable poly(l-lactide-co-D,L-lactide) (PLDLLA) cage devices have potential
      benefits over autologous tricortical iliac crest bone graft and metallic cages
      for cervical spine interbody fusion. The purpose of this study was to compare
      interbody fusion of an autologous tricortical iliac crest bone graft with that of
      a bioabsorbable cage using a sheep cervical spine interbody fusion model. This
      study was designed to determine differences in (1) the ability to preserve
      postoperative distraction, (2) biomechanical stability, and (3) histological
      characteristics of intervertebral bone matrix formation. Sixteen full-grown
      Merino sheep underwent C3/4 discectomy and fusion. After 12 weeks, there was no
      significant difference between the results with the bioabsorbable PLDLLA cages
      and tricortical bone grafts. The cage also did not show advanced interbody fusion
      but did, however, show large osteolysis, which allows skepticism regarding the
      value of this bioabsorbable implant.

PMID- 15146284
TI  - [Does routine angiographic control make sense after percutaneous coronary
      intervention?].
AB  - BACKGROUND AND PURPOSE: Is it possible to avoid routine coronary angiography
      after previous coronary intervention, if angiography is done only on patients
      with pathologic or questionable results in noninvasive diagnostic tests (recent
      medical history, exercise electrocardiography)? PATIENTS AND METHODS: During the
      period from January 1996 until December 2000, all patients who underwent
      interventional treatment of coronary vessels (n = 509) were routinely reexamined
      by coronary angiography within 3-6 months. Out of the total group as well as out
      of the patients with normal exercise electrocardiography, all patients with
      significant restenosis or new stenosis were identified. Patients with pathologic
      exercise electrocardiography and patients who could not tolerate exercise
      electrocardiography were marked. RESULTS: Out of 509 control angiograms, 105
      restenoses, 15 new stenoses and four patients with both a restenosis plus
      additional new stenosis were found. 92% of these patients underwent a new
      coronary intervention. Results of exercise electrocardiography in 477 patients
      were evaluated. In 276 patients (58%), exercise electrocardiography could not at
      all or not satisfactorily be carried out. In 97 patients (20%), exercise
      electrocardiography proved pathologic. In a total of only 201 patients, valid
      results of exercise electrocardiography could be utilized. Exercise
      electrocardiography, in these cases, had a sensitivity of 68% and a specificity
      of 60%. 18% of 104 patients with normal exercise electrocardiography and 24% of
      all patients had a significant coronary stenosis. CONCLUSION: In 21% of patients
      with coronary intervention, a recurrent stenosis was present in the area of
      previous treatment. These results equal those in the literature. In almost 60% of
      patients, a usable exercise electrocardiography could not be carried out. In 20%,
      this test showed pathologic findings. If, in addition to exercise
      electrocardiography, no other noninvasive tests were used, an indication for
      angiographic control was found in 80% of patients. False-negative exercise
      electrocardiography results were seen in 18%. Looking at medical history and
      exercise electrocardiography results as indication for angiographic control for
      routine coronary angiography, a saving of almost 22% of coronary angiograms could
      be realized. On the other hand, 16% of all patients with recurrent or new
      stenoses would be missed. These data show the clinical reality in a major medical
      center without a special department of cardiology. They match the data in the
      literature.

PMID- 15146285
TI  - [Glomerular-type proteinuria in hantavirus nephritis].
AB  - BACKGROUND: Infection with hantavirus of the Puumala type is known to cause
      severe illness, fever, loin pain and impaired vision. Tubulointerstitial
      nephritis leads to acute renal failure. CASE REPORTS: In four patients presenting
      with hantavirus infection and acute renal failure, proteinuria was analyzed by
      microelectrophoresis to explore possible causes of renal protein loss in
      hantavirus nephritis. The patients (three men, one woman) presented with a short
      history of fever, headache, loin pain and acute renal failure (enlarged kidneys
      in ultrasonography, serum creatinine 7.7/3.4/3.2/7.8 mg/dl, urinary protein
      excretion 1.7/0.5/1.5/9.0 g/l, IgM antibodies against hantavirus positive in all
      patients, subtype Puumala). Microelectrophoresis of the urine revealed a major
      fraction of higher molecular weight proteins such as transferrin and
      immunoglobulins indicating unselective glomerular-type proteinuria in all four
      patients. In three renal biopsy specimens obtained, morphology of glomeruli and
      vasculature was normal as judged by light microscopy. The tubulointerstitium
      exhibited interstitial hemorrhage and round-cell infiltrates. After 2 weeks,
      renal function had completely recovered in all patients and no persistent
      proteinuria developed. CONCLUSION: Hantavirus nephritis may lead to glomerular
      type proteinuria. Glomerular morphology may be normal and proteinuria may cease
      within 2 weeks indicating a transient lesion of the glomerular filtration
      barrier. Transiently increased glomerular permeability may be caused by an
      immunologic response to virus infection.

PMID- 15146287
TI  - [Heartburn--a symptom or an illness?].

PMID- 15146286
TI  - [Glucocorticoid receptors: basis for the diverse clinical actions of
      glucocorticoids].
AB  - Domain structure of the receptor polypeptide and association with accessory
      proteins: This review summarizes our present knowledge on the different forms of
      the glucocorticoid receptor emphasizing structure and functional significance.
      The nonactivated receptor resides in the cytoplasm. It contains the human
      receptor polypeptide of 777 amino acids as heteromeric complex in association
      with two molecules of the heat-shock protein hsp90 and one immunophilin. After
      binding the hormonal ligand, the receptor becomes activated by dissociation of
      these accessory proteins. The receptor functions as transcriptional regulator:
      The receptor polypeptide itself, complexed with hormone, moves on into the cell
      nucleus to there interact with chromatin and to affect transcriptional processes.
      By binding as homodimer to specific response elements on the DNA, the receptor
      functions as positive transcription factor causing increased expression of tissue
      specific genes. Alternatively, the receptor interacts with transcription factors
      like AP-1 or NF-kappaB and inhibits their effects on actively transcribed genes.
      Pharmacological considerations: The pharmacological possibilities of influencing
      the diverse medical actions of glucocorticoids are discussed on the level of
      receptors.

PMID- 15146288
TI  - [Infectious diseases-Part II: New agents, resistances, and treatment strategies].
AB  - A number of new antimicrobial agents have been licensed in the last years, most
      prominently a number of new antiviral and antimycotic agents. The development of
      new antibacterial agents has slowed down, new agents are mainly targeted at a
      small but rapidly growing number of patients infected with bacteria resistant to
      the current antibiotics. The rates of resistance against antibiotics are rapidly
      rising, especially for gram-positive cocci and, in addition, for gram-negative
      nosocomial agents. Rising rates of resistances are further present in chronic
      viral infections, e. g., HIV infection. Instruments to monitor and minimize the
      rates of resistances are necessary. Important changes are to be found in a number
      of infectious complications. For patients with sepsis a new therapeutic
      principle, drocretogrin, has been found to reduce mortality. Additionally, low
      dose corticosteroids in selected patients, close control of blood sugar and other
      interventions have shown to be effective. Corticosteroids have proven to be
      effective as well in the reduction of complications in adults with bacterial
      meningitis, most pronounced in pneumococcal meningitis. With new drugs licensed
      for the treatment of malaria and changes in the epidemiology, the guidelines for
      therapy and prevention have been reformulated.

PMID- 15146289
TI  - [Increased epistaxis with progressive malaise. Arteriovenous malformation of the
      lung].

PMID- 15146290
TI  - [Self-help and consultation via Internet. Self-responsible users redefine the
      physician-patient relationship].
AB  - Using e-health portals to the internet seeking information about one's illness
      and to exchange experience with other sick persons can result in more self
      responsible patients and in a more partnership-based physician-patient
      relationship. Especially with serious and chronic diseases like cancer, HIV
      infection, eating disorders, and depression, concerned patients may find support
      by accessing web pages and by using internet communication like message boards,
      mailing lists, and chat rooms. In an online questionnaire, internet users with
      eating disorders stated that they felt understood by their internet peers and,
      therefore, were encouraged to start therapy. Physicians may fear their advance in
      knowledge to decrease, resulting in an overprotective attitude to the informed
      patient. Nevertheless, they will recognize, by active participation, that the
      medical internet may promote an earlier start of expert-guided therapy, improved
      compliance, aftercare, and basic care independent of place and time. However,
      further evaluation of internet-supported treatment is required.

PMID- 15146291
TI  - [Internal medicine and geriatric boundaries, supplementation, transgression.
      Report on a combined Professional Congress of Internists and Geriatric
      specialists].

PMID- 15146292
TI  - CT virtual reality in the preoperative workup of malunited distal radius
      fractures: preliminary results.
AB  - Our objective was to evaluate the usefulness of CT virtual preoperative planning
      in the surgical repositioning of malunited distal radius fracture. Eleven
      patients with malunited distal radius fracture underwent multislice CT of both
      wrists. A preoperative workup was performed in a virtual reality environment
      created from the CT data sets. Virtual planning comprised three main procedures,
      carrying out the virtual osteotomy of the radius, prediction of the final
      position of the distal radius after osteotomy and computer-assisted manufacturing
      of a repositioning device, which was later placed at the surgical osteotomy site
      to reposition objectively the distal radius fragment before fixation with the
      osteosynthesis. All patients tolerated the surgical procedure well. During
      surgery, the orthopedic surgeons were not required in any of the cases to alter
      the position of the distal radius that was determined by the repositioning
      device. At postoperative follow-up, the anatomic relationship of the distal
      radius was restored (radial inclination, 21.4 degrees ; volar tilt, 10.3 degrees
      ; ulnar variance, 0.5 mm). Clinically, a significant improvement of pronation
      (P=0.012), supination (P=0.01), flexion (P=0.001) and extension (P=0.006) was
      achieved. Pain decreased from 54 to 7 points. CT virtual reality is a valuable
      adjunct for the preoperative workup and surgical reposition of malunited distal
      radius fractures.

PMID- 15146294
TI  - Strategies for antigen choice and priming of dendritic cells influence the
      polarization and efficacy of antitumor T-cell responses in dendritic cell-based
      cancer vaccination.
AB  - Dendritic cells (DCs) primed with tumor antigens (Ags) can stimulate tumor
      rejection. This study was aimed at evaluating the polarization of T-cell
      responses using various DC Ag-priming strategies for vaccination purposes. DCs
      cocultured with irradiated "apoptotic" tumor cells, DC-tumor fusions, and DCs
      pulsed with freeze-thaw tumor lysate Ags served as Ag-primed DCs, with EG7 tumor
      cells (class II negative) expressing OVA as the model Ag. DCs loaded with class I
      and class II-restricted OVA synthetic peptides served as controls. Primed DCs
      were assessed by the in vitro activation of B3Z OVA-specific CD8 T cells and the
      proliferation of OVA-specific CD8 and CD4 T cells from OT-I and OT-II TCR
      transgenic mice, respectively. In vivo responses were measured by tumor
      regression following treatment with Ag-primed DCs and by CTL assays.
      Quantification of IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha by cytometric bead
      array (CBA) assay determined the polarization of TH1/TH2 responses, whereas H-2
      Kb/SIINFEKL tetramers monitored the expansion of OVA-specific T cells. DC-EG7
      hybrids stimulated both efficient class I and class II OVA responses, showing
      that DC-tumor hybrids are also capable of class II cross-presentation. The
      hybrids also induced the most potent CTLs, offered the highest protection against
      established EG7 tumors and also induced the highest stimulation of IFN-gamma and
      TNF-alpha production. DCs cocultured with irradiated EG7 were also effective at
      inducing OVA-specific responses, however with slightly reduced potency to those
      evoked by the hybrids. DCs loaded with lysates Ags were much less efficient at
      stimulating any of the OVA-specific T-cell responses, showed very little
      antitumor protection, and stimulated a weak TH1 response, overbalanced by an IL-5
      TH2 response. The strategy of Ag-loading clearly influences the ability of DCs to
      polarize T cells for a TH1/TH2 response and thus determines the outcome of the
      elicited immune response, during various vaccination protocols.

PMID- 15146293
TI  - The three-dimensional microstructure of the trabecular bone in the mandible.
AB  - This study investigated the three dimensional (3D) trabecular microstructure of
      the alveolar and basal bone in the mandible using micro-CT and compared the
      morphometric values of the different sites. Ten specimens were prepared and
      scanned using a micro-CT system. Both the alveolar and basal trabecular bone of
      the premolar region in the mandible were measured for the structural analysis.
      Cross-sectional 1024x1024 pixel images were created. From the two-dimensional
      (2D) images produced, 3D structural images were reconstructed. After scanning the
      specimen, the volumes of interest (VOI) of the alveolar and basal bone regions
      were selected from the 3D reconstruction images, and the structural parameters
      such as bone volume fraction, bone surface density, trabecular thickness,
      trabecular separation, trabecular number and structural model index were
      analyzed. The trabecular structure showed a marked variation within the sites of
      the specimen, especially in the basal trabecular bone inferior to the mandibular
      canal. In both the alveolar and basal bone regions, a mixture of both plate-like
      and rod-like structures was observed. The alveolar region showed a more compact,
      plate-type trabecular structure than the basal regions. In parametric comparison
      with the basal bone, the alveolar bone generally had a higher bone volume
      fraction, bone trabecular thickness and trabecular number, and lower bone surface
      density, trabecular separation and structural model index. The alveolar bone
      consisted of a compact bone structure with a large amount of thick plate-type
      trabecular bone, which was effectively resistant to the masticatory forces. As
      the measurements were made closer to the basal bone, a loose structure was
      observed with lower bone volume and fewer, thin, rod-like trabeculae.

PMID- 15146295
TI  - FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast
      cancer.
AB  - Breast cancer continues to be one of the most common cancers in North America and
      Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy
      D-glucose (FDG PET) represents a non-invasive functional imaging modality that is
      based on metabolic characteristics of malignant tumours. In breast cancer, FDG
      PET is more accurate than conventional methods for staging of distant metastases
      or local recurrences and enables early assessment of treatment response in
      patients undergoing primary chemotherapy. Recent data indicate a rationale for
      the use of FDG PET in cases of asymptomatically elevated tumour marker levels in
      the presence of uncertain results of conventional imaging. Despite the fact that
      PET cannot rule out microscopic disease, it does have particular value in
      providing, in a single examination, a reliable assessment of the true extent of
      the disease. This technique is complementary to morphological imaging for primary
      diagnosis, staging and re-staging. It may become the method of choice for the
      assessment of asymptomatic patients with elevated tumour marker levels. This
      method, however, cannot replace invasive procedures if microscopic disease is of
      clinical relevance.

PMID- 15146296
TI  - Cultivation of immobilized Dictyostelium discoideum for the production of soluble
      human Fas ligand.
AB  - Dictyostelium discoideum was immobilized by cultivation on inorganic porous
      matrices consisting of broken pumice or a ceramic catalyst carrier (CeramTec) to
      produce human soluble Fas ligand (hFasL). These supports were actively colonized
      by D. discoideum reaching cell (number) densities 10-20 times higher locally than
      those observed in suspension culture under similar conditions. In repeated batch
      or continuous operation, hFasL productivities of up to 15-25 microg h(-1) l(-1)
      pore volume were attained. The immobilized cell densities and hFasL
      productivities could be kept constant for a long period of time by repeated
      renewal or continuous feeding of complex or synthetic medium.

PMID- 15146297
TI  - Early expression of two TdT isoforms in the hematopoietic system of the Mexican
      axolotl. Implications for the evolutionary origin of the N-nucleotide addition.
AB  - Nontemplate (N)-nucleotide addition by the terminal dideoxynucleotidyl
      transferase (TdT) at the junctions of rearranging V( D) J gene segments greatly
      contribute to antigen-receptor diversity. TdT has been identified in several
      vertebrate species, where it is highly conserved. We report here the isolation of
      two forms of TdT mRNA in an amphibian, the Mexican axolotl. The isoform TdT1
      shares all of the conserved structural motifs required for TdT activity and
      displays an average of 50-58% similarity at the amino acid level with TdT of
      other species. The second axolotl TdT variant ( TdT2) differs from TdT1 by a 57
      amino acid deletion located between amino acids 165-222 of TdT1, including the
      first helix-hairpin-helix DNA-binding motif. During ontogeny, TdT products are
      first detected in the head of 6-week-old larvae and further in the head and trunk
      of 8-month-old larvae. These developmental stages correspond to the first
      detection of RAG1 and antigen-receptor (TCRbeta and IgHmicro) products in axolotl
      larvae. Our results suggest that in contrast to mammalian development, N
      diversity occurs early in axolotl development to diversify the primary
      repertoire. Phylogenetic analyses reveal that TdT and DNA polymerase mu(Pol mu)
      genes are closely related, and that both enzymes were already present in the
      common ancestor of jawed vertebrates.

PMID- 15146298
TI  - A molecular dynamics simulation study of polyamine- and sodium-DNA. Interplay
      between polyamine binding and DNA structure.
AB  - Four different molecular dynamics (MD) simulations have been performed for
      infinitely long ordered DNA molecules with different counterions, namely the two
      natural polyamines spermidine(3+) (Spd3+) and putrescine(2+) (Put2+), the
      synthetic polyamine diaminopropane(2+) (DAP2+), and the simple monovalent cation
      Na+. All systems comprised a periodical hexagonal cell with three identical DNA
      decamers, 15 water molecules per nucleotide, and counterions balancing the DNA
      charge. The simulation setup mimics the DNA state in oriented DNA fibers,
      previously studied using NMR and other experimental methods. In this paper the
      interplay between polyamine binding and local DNA structure is analyzed by
      investigating how and if the minor groove width of DNA depends on the presence
      and dynamics of the counterions. The results of the MD simulations reveal
      principal differences in the polyamine-DNA interactions between the natural
      [spermine(4+), Spd3+, Put2+] and the synthetic (DAP2+) polyamines.

PMID- 15146300
TI  - Formation and transformation of struvite and newberyite in aqueous solutions
      under conditions similar to physiological.
AB  - The precipitation of magnesium phosphates in the system MgCl(2)-NH(4)H(2)PO(4)
      NaOH-H(2)O was studied at a wide range of reactant concentrations at 37 degrees C
      and an initial pH(i) of 7.4. Precipitates were aged for 24 h and characterized by
      means of optical and scanning electron microscopy, x-ray diffractometry, FT-IR
      spectroscopy and thermogravimetry. Struvite was found to precipitate in nearly
      the whole concentration region investigated. Pure newberyite and a mixture of
      struvite and newberyite were obtained in a narrow range only with a pH(24 h)<6.4.
      The transformation of struvite into newberyite was studied by following changes
      in the liquid and solid phases. Thus, the changes of pH and the content of
      struvite in the precipitate as a function of time were recorded. The influence of
      the initial pH(i) and temperature on the transformation process is discussed.
      Analysis of the experimental data suggests a solution mediated transformation
      process as a possible mechanism of struvite transformation.

PMID- 15146299
TI  - Detection of Helicobacter pylori in bladder biopsy specimens of patients with
      interstitial cystitis by polymerase chain reaction.
AB  - The cause of interstitial cystitis (IC) is still unknown. Several features
      suggest that it may be an infectious disease and it has compelling similarities
      to chronic gastritis. The identification of Helicobacter pylori as the cause of
      chronic gastritis focused attention on this organism. Many studies have been done
      investigating the role of H. pylori in the etiology of IC. Previous studies
      mostly determined the presence of H.pylori with antibodies in the serum samples
      of IC patients, but these methods may lead to false positive or negative results.
      We therefore investigated the presence of H.pylori in bladder biopsy specimens by
      using polymerase chain reaction (PCR), which is accepted as the most sensitive
      and specific test for detecting this organism. A total of 32 patients with IC
      were enrolled into the study. The PCR assay was performed on cold cup bladder
      biopsies of IC patients. Both positive and negative controls were included in
      each set of PCR reactions. Gastric biopsy specimens of peptic ulcer patients with
      proven H. pylori infection were used as positive controls. Bladder biopsies of
      all IC patients were negative for H. pylori DNA. PCR showed the presence of H.
      pylori in the positive controls in each cycle demonstrating that the PCR assay
      was working properly. Thus, there is no evidence that IC is the result of H.
      pylori infection. This study does not negate the possibility that other
      infectious agents may play a role in the etiology of IC.

PMID- 15146303
TI  - Restricted indications for the use of antibiotics in acute otitis media.

PMID- 15146302
TI  - Off-label prescribing to children in primary care: retrospective observational
      study.
AB  - OBJECTIVES: To investigate the extent and pattern of off-label prescribing to
      children in primary care throughout Scotland. DESIGN: Assessment of prescribing
      to 167,865 children aged 0-16 years during the period November 1999 to October
      2000 using data from 161 general practices using the national Scottish primary
      care computer system General Practice Administration System for Scotland.
      SETTING: One hundred and sixty one general practices in Scotland. RESULTS: During
      the study period, at least one off-label prescription was issued to 17,715
      (26.1%) children aged 0-16 years. Off-label prescribing due to lower than the
      recommended dose was the most common form of off-label prescribing (40-50%), with
      antibiotics and antihistamines making up the majority. Off-label prescribing due
      to higher than the recommended dose was also common (35% of all off-label
      prescribing), with antiasthmatics, topical corticosteroids and laxatives making
      up the majority. Off-label prescribing with respect to age was less common (6
      16%) affecting mainly young children (less than 2 years old) and adolescents. Off
      label prescribing with respect to formulation was the least common cause
      accounting for 5-10% of off-label prescribing. CONCLUSIONS: This is the largest
      and most detailed study to date of paediatric off-label prescribing in primary
      care within the UK. Such off-label prescribing likely occurs as the result of
      several factors including a failure to update licensing information with
      currently accepted practice and confusion or unawareness of the licensing
      recommendations, further compounded by a lack of clinical trials data and
      suitable formulations for medicines commonly prescribed to young children and
      adolescents.

PMID- 15146304
TI  - Expected and unexpected head yaw movements result in different modifications of
      gait and whole body coordination strategies.
AB  - During locomotion we routinely make voluntary head movements, similar to those
      made during steering tasks, in order to scan our environment and obtain
      information about objects in the environment and our proximity to these objects.
      Given the importance that head segment orientation during locomotion has received
      in the recent literature, two studies were designed to investigate responses
      following a voluntarily generated and an unexpected, externally applied head
      turn. During a voluntary head turn, an efferent copy of the head movement could
      cancel the sensory effects of the head turn, effectively isolating the movement
      response to that segment. Alternatively, if the steering synergy is a part of our
      motor repertoire, as has been suggested, movement of the head could automatically
      release a steering "synergy" of segmental control and coordination. A unique head
      mounted air-jet apparatus, designed and developed at the University of Waterloo,
      was used for both studies to ensure that auditory stimuli and the physical
      presence of the apparatus on the head were similar for participants of the two
      experiments. During certain points in the gait cycle, this device was triggered
      and a short burst of compressed air (350 ms) was released to cue participants to
      make a voluntary head turn (Experiment 1). The same device was triggered in
      Experiment 2; however, in this experiment compressed air was released for a
      longer duration (1,500 ms) which resulted in an unexpected and quick turn of the
      participants' head to either the left or right. In these experiments, vision was
      also manipulated in certain trials with liquid crystal display glasses that
      occluded vision for the duration of the head turn. Data from the first experiment
      indicates that a subset of the steering synergy previously observed is released
      following the voluntary head movement; however, the travel trajectory path is
      preserved, suggesting that sensory input resulting from the head movement is
      partially nullified by the central nervous system. Overall safety is ensured by
      maintaining the same travel path. In the second experiment, an unexpected
      perturbation was applied to the head during locomotion to determine how the
      absence of an efferent copy of the movement pattern influences the level of
      control over body segments during locomotion. Whole body responses similar to
      those observed during steering tasks were observed following application of this
      unexpected head perturbation. It is proposed that the CNS interprets an
      unexpected yaw movement of the head as a change in the frame of reference, and
      global modifications of the walking trajectory, similar to that observed during
      steering tasks, are made in the perceived new direction of travel. Collectively
      this work extends our understanding of how the CNS establishes a head based
      orientation frame for locomotion. The CNS interprets and integrates anticipated
      and unexpected changes in sensory information from the head segment and
      subsequently modifies locomotion patterns according to the perceived whole body
      orientation in space. The sequence of control following these head movements
      appears to be part of a movement repertoire that is not immutable; maintaining
      whole body stability during locomotion is paramount.

PMID- 15146305
TI  - Effects of somatosensory electrical stimulation on neuronal injury after global
      hypoxia-ischemia.
AB  - Electrical stimulation (ES) is used after cardiac arrest (CA) for diagnostic and
      therapeutic purposes. The effects of ES on brain damage induced by hypoxic
      ischemic brain injury (HI) has not been investigated. Stimulation of afferent
      pathways by ES may increase neural injury by releasing excitatory
      neurotransmitters (glutamate) and thereby exacerbating excitotoxicity. To test
      this hypothesis, ES was applied to the median nerve (2 h) of adult male Wistar
      rats after 5 min of asphyxic CA and cardiopulmonary resuscitation. Control
      animals received no ES. Assessment of neuronal damage in five regions of interest
      was performed in survivors (ESn=15, Control n=10, Sham n=3) after 48 h using H&E,
      Cresyl-Violet, and TUNEL stains, and Caspase-3 and activated ERK 1/2
      immunohistochemistry. Ratios of injured to normal cells were calculated. Most
      injury was found in hippocampus and cerebellum. ES animals showed significantly
      lower injury ratios in bilateral hippocampus as compared with controls (F=20.8,
      p<0.00001). TUNEL staining, caspase-3 and activated ERK 1/2 showed no differences
      between groups. It is concluded that ES during the acute phase of HI does not
      amplify neuronal damage at 48 h, but may have a protective effect that requires
      further investigation.

PMID- 15146306
TI  - Modulation of motor unit discharge rate and H-reflex amplitude during submaximal
      fatigue of the human soleus muscle.
AB  - Declining motor unit discharge rates and H-reflex amplitude have been observed in
      separate experiments during fatiguing submaximal contractions in humans. The
      purpose of this experiment was to investigate motor unit discharge rate, H-reflex
      amplitude, and twitch contractile properties concurrently during a fatiguing
      submaximal isometric contraction of the ankle plantarflexors. Eleven healthy
      subjects performed fatiguing contractions of low force (25% maximal voluntary
      contraction (MVC)) or high force (42-66% MVC). Hoffmann (H)-reflexes, muscle
      compound action potentials (M-waves), twitch contractile properties, and motor
      unit discharges were recorded from the soleus muscle. In the low-force fatigue
      task, motor unit firing rate increased gradually over time, whereas the resting H
      reflex was significantly depressed at 15% of endurance time and remained
      quasiconstant for the rest of the task. This suggests that the processes
      mediating the resting H-reflex depression are relatively independent of those
      modulating the motor unit firing rate during a low-force fatigue task. In the
      high-force fatigue task, a decline in the average motor unit discharge rate was
      accompanied by a decrease in the resting H-reflex amplitude and a prolongation of
      the twitch half-relaxation time (HRT) at the completion of the fatigue task.
      Overall, motor unit firing rate was modulated in parallel with changes in the
      twitch HRT, consistent with the muscle wisdom hypothesis.

PMID- 15146307
TI  - Surround inhibition in human motor system.
AB  - In sensory systems, a neural mechanism called surround inhibition (SI) sharpens
      sensation by creating an inhibitory zone around the central core of activation.
      In the motor system, the functional operation of SI remains to be demonstrated,
      although it has been hypothesized to contribute to the selection of voluntary
      movements. Here we test this hypothesis by using transcranial magnetic
      stimulation of the human motor cortex. The motor evoked potential of the little
      finger muscle is suppressed or unchanged during self-paced, voluntary movements
      of the index finger, mouth or leg, despite an increase in spinal excitability.
      This result indicates that motor excitability related to little finger movement
      is suppressed at the supraspinal level during these movements, and supports the
      idea that SI is an organizational principle of the motor system.

PMID- 15146308
TI  - Fluorescence enhancement method for measuring anionic surfactants with a
      hydrophobic cyanine dye.
AB  - A novel fluorimetric method based on use of a hydrophobic cationic cyanine dye
      has been developed for determination of the anionic surfactant sodium
      dodecylbenzenesulfonate (DBS). The method is based on the enhancement effect of
      DBS on the fluorescence of the hydrophobic cyanine dye 2-[-4'-chloro-7'-(1"-ethyl
      3",3"-dimethylindolin-2"-ylidene)-3',5'-(propane-1"',3"'-diyl)-1',3',5'
      heptatrien-1'-yl]-1-ethyl-3,3-dimethyl-3 H-indolium iodide. Under the optimum
      conditions the extent of fluorescence enhancement is proportional to the
      concentration of DBS in the range 0.05-5.0 mg L(-1); the detection limit is 0.014
      mg L(-1). The relative standard deviation for 0.35 mg L(-1) DBS was 1.1% (n=10).
      The proposed method, which avoided use of toxic solvents and tedious solvent
      extraction, and was applied to the determination of DBS in natural water with
      recoveries between 99.9 and 107%. Preliminary research shows that the
      fluorescence enhancement is due to the formation of a dye aggregate facilitated
      by DBS.

PMID- 15146310
TI  - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on maternal immune response
      during pregnancy.
AB  - Whether pregnancy-induced immunosuppression when combined with exposure to
      2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) could exacerbate immunotoxicity has
      not been previously investigated. The current study evaluated the immune status
      of C57BL/6 pregnant and virgin mice following exposure to TCDD. To this end,
      syngeneically pregnant or virgin female mice were injected intraperitoneally with
      10 micro g/kg TCDD. Pregnancy alone significantly decreased thymic cellularity
      and J11d expression as well as induced changes in T-cell subsets. TCDD treatment
      caused significant thymic atrophy in pregnant mice as early as 48 h after
      exposure, but this effect was apparent in virgin mice only after 72 h. TCDD
      treatment also caused more marked alterations in thymic T-cell subpopulations of
      pregnant mice when compared to the virgin mice, with a decrease in the percentage
      of double-positive T cells and an increase in the percentage of single-positive
      (sP CD4(+) or sP CD8(+)) and double-negative T cells. Moreover, the proliferative
      responses of thymocytes, but not splenocytes, to mitogens were significantly
      altered in TCDD-treated pregnant mice when compared to the TCDD-treated virgin
      mice. Furthermore, no significant changes in the expression of CD4, CD8, B220 and
      NK1.1 markers were found in splenocytes from TCDD-treated virgin and pregnant
      mice. Immunization of mice with a superantigen caused a similar immunotoxic
      response in TCDD-treated pregnant and virgin mice with a decreased lymph node
      cellularity and lower percentages and cell numbers of Vbeta3(+) and Vbeta11(+) T
      cells. Together, the results of the current study demonstrate for the first time
      that pregnancy augments the sensitivity to TCDD-induced immunotoxicity in the
      thymus, but not in secondary lymphoid organs.

PMID- 15146311
TI  - Treatment of full thickness chondral lesions of the knee with microfracture in a
      group of athletes.
AB  - This prospective outcomes study was designed to prospectively investigate the
      outcome of the microfracture technique when applied to full thickness chondral
      lesions of the knee in a group of athletes. From 1991 to 1999, 109 patients were
      treated using the microfracture technique. We prospectively followed up 53
      athletes who satisfied our inclusion criteria. Average age was 38 years (range 19
      55) and mean follow-up was 72 months (range 36-120). Etiology, clinical signs,
      symptoms and activity level were noted preoperatively and at final follow-up.
      Lysholm, Tegner, IKDC and functional tests were utilized. Intraoperatively,
      location, size of the lesions and associated pathologies were recorded.
      Roentgenograms, MRI or CT scan were done before treatment and at final follow-up.
      Etiologic factors were mostly related to sports microtrauma (37.5%) and
      macrotrauma (21%), while 37.5% of our patients did not report any traumatic
      etiology and 4% showed patellar malalignment. The most common location was medial
      femoral condyle (61%). Knee pain and swelling improved in 70%, tibiofemoral
      crepitus in 60%. Hop test was normal in 70% at final follow-up. Subjective
      evaluation was 40/100 preoperatively and 70/100 at final follow-up. Lysholm was
      56.8 preoperatively and 87.2 final. IKDC revealed: 0 A, 3 B, 40 C and 10 D
      preoperatively while at final follow-up 70% scored A or B. Tegner improved at 2
      years from 3.2 to 6; however, at final follow-up 80% showed a decline in sport
      activity level (Tegner 5). Microfracture technique can offer clinical, functional
      and subjective improvement in athletically active patients. However because of
      the decline in sports participation over time, microfracture may not be the
      definitive procedure for the athlete's knee and other procedures may be indicated
      in the future.

PMID- 15146309
TI  - Disturbed atrio-ventricular conduction and normal contractile function in
      isolated hearts from Cav1.3-knockout mice.
AB  - Cardiac L-type calcium channels are formed by two alpha-subunits, Cav1.2
      (alpha(1C)) and Cav1.3 (alpha(1D)). In contrast to the uniform expression pattern
      of Cav1.2, Cav1.3 is highly expressed in sino-atrial node (SAN) and atrial
      tissue, but not in the ventricle. Accordingly, knockout of Cav1.3 (Cav1.3(-/-))
      in mice was shown to lead to a cardiac phenotype characterised by severe
      bradycardia in vivo and in isolated SAN cells. Cav1.3 may therefore constitute a
      novel pharmacological target for specific bradycardic agents. RNAse protection
      assays of murine wild type hearts revealed rather high Cav1.3 levels comparable
      to Cav1.2, suggesting functional relevance of Cav1.3 outside specialised tissues
      such as SAN. Due to the lack of specific Cav1.3 blockers, we directly examined
      the functional role of Cav1.3 using isolated working hearts from adult wild type
      (WT) and Cav1.3(-/-) mice. Histological analysis of hearts revealed no
      pathological changes. Ventricular contractility and inotropic effects of
      isoproterenol were unaltered in Cav1.3(-/-) hearts. Severe sinus bradycardia
      already noted in vivo was accompanied by ventricular extrasystoles. This
      phenotype was restored to nearly normal values by the cumulative addition of
      isoproterenol. Electrocardiograms of Cav1.3(-/-) hearts revealed delayed atrio
      ventricular (AV) conduction and a decoupling of heart rate and PR interval
      duration. Isoproterenol did not improve disturbance of AV conduction. In
      conclusion, suppression of Cav1.3 does not alter ventricular contractile
      function, and the decrease in sinus node frequency is counterbalanced by
      adrenergic stimulation. Importantly, bradyarrhythmia is partly due to an
      intrinsic AV node dysfunction, which is resistant to adrenergic counterbalance.
      These findings help to predict the clinical pattern of selective Cav1.3 blockade.

PMID- 15146313
TI  - Effect of University of Wisconsin organ-preservation solution on haemorheology.
AB  - In conventional cold-storage organ preservation, the donor organ is flushed with
      University of Wisconsin (UW) solution at 0-4 degrees C. The initial flush is used
      to wash out blood from the microcirculation to allow optimal preservation with
      the UW solution. The component hydroxyethyl starch (HES) of UW is known to cause
      relatively high viscosity and a possible interaction with blood, i.e. increased
      red blood cell (RBC) aggregation. The aim of this study was to investigate the
      influence of the HES component on the viscosity of UW and the aggregation
      behaviour of blood during washout. Viscosity aspects were measured with a cone
      plate rheometer. HES-induced RBC aggregation was studied by means of an optical
      aggregation measuring device. The experiments were carried out with rat whole
      blood and mixtures of rat whole blood with UW-solution and UW without HES
      (UWmod), at 4 degrees C. The viscosity of blood at 4 degrees C is two-times
      higher than at 37 degrees C; the UW/blood mixture at 4 degrees C is 1.3-times
      more viscous than blood at 37 degrees C; the 4 degrees C UWmod/blood mixture
      equals the viscosity of blood at 37 degrees C. The UW/blood mixture shows a
      ninefold increased aggregation compared with whole blood. These aggregates are
      larger than the diameter of the sinusoids in the rat liver. A mixture of whole
      blood and UWmod shows a lower aggregation than blood. Apart from an increased
      viscosity, HES in UW causes increased RBC aggregation. The aggregates are larger
      than the diameter of the sinusoids. Initial washout could be optimised by pre
      flushing to improve the viability of the liver and to decrease delayed graft
      function.

PMID- 15146314
TI  - Early-morning urine osmolality in patients with chronic allograft nephropathy.

PMID- 15146312
TI  - Normal and transplanted lateral knee menisci: evaluation of extrusion using
      magnetic resonance imaging and ultrasound.
AB  - The aim of the study is to develop a clinically useful and reproducible method
      for evaluating lateral meniscal extrusion in normal and transplanted knees under
      different axial loading conditions. Magnetic resonance imaging (MRI) and
      ultrasound (US) were used to assess meniscal extrusion. Both types of imaging
      were performed at least 6 months postoperatively (mean 23.5 months). Coronal MR
      images (DESS-3D sequence) of the lateral compartments of 10 normal knees and 17
      transplanted lateral knees were analyzed. Extrusion was defined as the distance
      measured from the femoral condyle or tibial plateau to the outer edge of the
      meniscus. Subjects were examined in the supine position. Ultrasound print-outs of
      the lateral compartment of both knees of ten patients (transplanted side and
      contralateral normal side) were analyzed. Extrusion cross-sectional area (CSA)
      and distance were measured just anterior to the lateral collateral ligament: the
      former was defined as the CSA of the meniscus outside the knee, the latter as the
      greatest distance from a line connecting the femur and tibia to the outer edge of
      the lateral meniscus. Patients were examined in the supine position, bipodal
      stance and unipodal stance. The viable meniscal allograft was securely sutured to
      a bleeding functional meniscal rim. No bone blocks were used to fix the
      allograft; instead, the anterior and posterior horn were firmly sutured to their
      enthesis. The MRI results (tibial) show the transplanted lateral meniscus to be
      significantly (p<0.005) more extruded in comparison to the normal lateral
      meniscus. The anterior horn (mean 5.8 mm, SD=2.8) of the transplanted lateral
      meniscus tends to be more extruded than the posterior horn (mean 2.7 mm,
      SD=1.48). The posterior horn of the normal lateral meniscus does not (mean 0 mm)
      extrude, while the mean extrusion of the anterior horn is 0.8 mm (SD=0.92). In
      the US results, the transplanted lateral meniscus is significantly (p<0.005) more
      extruded than the normal lateral meniscus in all patient positions. Both cross
      sectional surface and distance are equally good parameters to determine meniscal
      extrusion. There is no statistical difference between patient positions. The
      transplanted lateral meniscus extrudes, in the supine position, bipodal and
      unipodal stance 6.43 (SD=1.84), 6.01 (SD=1.93) and 6.99 mm (SD=2.7) respectively.
      The extrusion surface of the lateral transplanted meniscus is 50.50 mm2
      (SD=15.32), 47.24 mm2 (SD=14.35) and 58.61 mm2 (SD=29.65) in the supine position,
      bipodal stance and unipodal stance respectively. The normal lateral meniscus
      extrudes in the supine position, bipodal and unipodal stance 3.77 (SD=1.76), 3.94
      (SD=1.66) and 3.79 mm (SD=1.79) respectively. The extrusion surface of the normal
      lateral meniscus is 22.42 mm2 (SD=12.54), 23.24 mm2 (SD=12.74) and 24.79 mm2
      (SD=10.18) in the supine position, bipodal stance and unipodal stance
      respectively. The presented data shows that the transplanted lateral meniscus,
      without bone block fixation but with firm fixation of the horns to the original
      entheses, extrudes in the lateral direction significantly more than the normal
      meniscus. The transplanted lateral meniscus, however, does not extrude more in
      the lateral direction under axial load. The anterior horn of both normal and
      transplanted menisci is extruded more laterally than the posterior horn. Both
      methods are adequate to measure laterally-directed extrusion of the normal and
      transplanted lateral meniscus, but have distinctive advantages and disadvantages:
      MRI in this series visualizes the complete-from posterior to anterior-meniscal
      body, but only in the supine, non-weight-bearing position. Using ultrasound one
      can evaluate the meniscal extrusion in different conditions of axial loading, but
      only from a single examination point.

PMID- 15146316
TI  - Single nucleotide polymorphism, haplotype diversity and recombination in the Isa
      gene of barley.
AB  - The Isa gene from barley--an intronless gene expressed in maternal tissues of the
      seed--has a likely role in defence against pathogens. The protein product--bi
      functional alpha-amylase/subtilisin inhibitor--inhibits the seed's own amylase in
      addition to the bacterial protease subtilisin and fungal xylanase. Sixteen barley
      genotypes were targeted to amplify and sequence the Isa gene region to detect
      sequence polymorphisms, since little is known about genetic diversity at this
      locus. A total of 80 single nucleotide polymorphisms (SNPs) and 23 indels were
      detected in 2,164 bp of sequence containing the Isa transcript, promoter and 3'
      non-transcribed region (overall one SNP per 27 bp and one indel per 94 bp), with
      eight sequence-based haplotypes distinguishable amongst the 16 varieties.
      Sequencing a polymorphic region in the promoter in an additional 27 barley
      genotypes increased the number of sequence-based haplotypes discovered to 11.
      However there is low haplotype diversity amongst the cultivated barley varieties
      sampled, with most varieties represented by a single haplotype. There was minor
      amino acid diversity in the protein, with five out of ten SNP sites in the coding
      region predicted to produce amino acid substitutions. SNP analysis indicated a
      history of recombination events--a minimum of seven based on the initial eight
      haplotypes from the whole sequenced region. Most of the recombination events
      occurred in the highly polymorphic regions, the 3' non-transcribed region and
      sequences flanking a microsatellite in the Isa promoter.

PMID- 15146315
TI  - [Lesions of the wrist disc. Pathology, diagnosis and treatment].
AB  - Lesions of the TFCC are currently a diagnostic and therapeutic challenge. Disc
      injuries are often not identified and, therefore, acute ruptures are
      unfortunately not always immediately repaired. Moreover, therapeutic measures are
      still sparse and informative trial results are lacking. An anatomical,
      pathological, diagnostic and therapeutic comparison with the meniscus of the knee
      is possible.

PMID- 15146317
TI  - Study of simple sequence repeat (SSR) markers from wheat expressed sequence tags
      (ESTs).
AB  - The increasing availability of expressed sequence tags (ESTs) in wheat ( Triticum
      aestivum) and related cereals provides a valuable resource of non-anonymous DNA
      molecular markers. We examined 170,746 wheat ESTs from the public (International
      Triticeae EST Cooperative) and Genoplante databases, previously clustered in
      contigs, for the presence of di- to hexanucleotide simple sequence repeats
      (SSRs). Analysis of 46,510 contigs identified 3,530 SSRs, which represented 7.5%
      of the total number of contigs. Only 74% of the sequences allowed primer pairs to
      be designed, 70% led to an amplification product, mainly of a high quality (68%),
      and 53% exhibited polymorphism for at least one cultivar among the eight tested.
      Even though dinucleotide SSRs were less represented than trinucleotide SSRs
      (15.5% versus 66.5%, respectively), the former showed a much higher polymorphism
      level (83% versus 46%). The effect of the number and type of repeats is also
      discussed. The development of new EST-SSRs markers will have important
      implications for the genetic analysis and exploitation of the genetic resources
      of wheat and related species and will provide a more direct estimate of
      functional diversity.

PMID- 15146318
TI  - Isolation of gibberellin metabolic pathway genes from barley and comparative
      mapping in barley, wheat and rice.
AB  - Gene sequences encoding gibberellin (GA) biosynthetic and catabolic enzymes were
      isolated from "Himalaya" barley. These genes account for most of the enzymes
      required for the core pathway of GA biosynthesis as well as for the first major
      catabolic enzyme. By means of DNA gel blot analysis, we mapped coding sequences
      to chromosome arms in barley and wheat using barley-wheat chromosome addition
      lines, nulli-tetrasomic substitution and ditelosomic lines of wheat. These same
      sequences were used to identify closely related sequences from rice, which were
      mapped in silico, thereby allowing their syntenic relationship with map locations
      in barley and wheat to be investigated. Determination of the chromosome arm
      locations for GA metabolic genes provides a framework for future studies
      investigating possible identity between GA metabolic genes and dwarfing genes in
      barley and wheat.

PMID- 15146319
TI  - Pathotype-specific genetic factors in chickpea (Cicer arietinum L.) for
      quantitative resistance to ascochyta blight.
AB  - Ascochyta blight in chickpea ( Cicer arietinum L.) is a devastating fungal
      disease caused by the necrotrophic pathogen, Ascochyta rabiei (Pass.) Lab. To
      elucidate the genetic mechanism of pathotype-dependent blight resistance in
      chickpea, F(7)-derived recombinant inbred lines (RILs) from the intraspecific
      cross of PI 359075(1) (blight susceptible) x FLIP84-92C(2) (blight resistant)
      were inoculated with pathotypes I and II of A. rabiei. The pattern of blight
      resistance in the RIL population varied depending on the pathotype of A. rabiei.
      Using the same RIL population, an intraspecific genetic linkage map comprising 53
      sequence-tagged microsatellite site markers was constructed. A quantitative trait
      locus (QTL) for resistance to pathotype II of A. rabiei and two QTLs for
      resistance to pathotype I were identified on linkage group (LG)4A and LG2+6,
      respectively. A putative single gene designated as Ar19 (or Ar21d) could explain
      the majority of quantitative resistance to pathotype I. Ar19 (or Ar21d) appeared
      to be required for resistance to both pathotypes of A. rabiei, and the additional
      QTL on LG4A conferred resistance to pathotype II of A. rabiei. Further molecular
      genetic approach is needed to identify individual qualitative blight resistance
      genes and their interaction for pathotype-dependent blight resistance in
      chickpea.

PMID- 15146320
TI  - Abrasion of eroded root dentine brushed with different toothpastes.
AB  - This study evaluated the surface roughness change and wear provided by different
      dentifrices on root dentine previously exposed to erosive challenges. According
      to a randomized complete block design, 150 slabs of bovine root dentine (6 x 3 x
      2 mm) were ground flat and polished. In an area of 4 x 3 mm on the dentine
      surface, specimens were submitted to five erosive/abrasive events, each one
      composed by: exposure to Sprite Diet or distilled water for 5 min, then to a
      remineralizing solution for 1 min, and simulation of 5,000 brushing strokes. Four
      dentifrices--regular (RE), baking soda (BS), whitening (WT) and tartar control
      (TC)--and distilled water (CO), used as control, were compared. Final texture and
      the wear depth were evaluated using a profilometer. ANOVA did not show
      significant interaction, indicating that the effect of dentifrices on both
      surface roughness change and wear did not depend on whether or not the dentine
      was eroded ( p>0.05). There was no difference between abrasion of eroded and
      sound dentine. The Tukey's test revealed that WT, BS and TC provided the highest
      increase in surface roughness differing from RE and CO. TC yielded the deepest
      wear of root dentine, whereas RE and CO, the shallowest. No significant
      difference in wear among BS, TC and WT were observed. Within the limitations of
      this study, the data showed that abrasion of both eroded and sound root dentine
      was dependent on the dentifrice used.

PMID- 15146322
TI  - Genetic and environmental variation in performance of a marine isopod: effects of
      eutrophication.
AB  - Environmental variation in food resources modifies performance of herbivores, in
      addition to genetic variation and maternal effects. In marine benthic habitats,
      eutrophication may modify herbivores' diets by changing host species composition
      or nutritional quality of algae for herbivores. We studied experimentally the
      effects of diet breadth and nutrient availability for the host algae on fitness
      components of the herbivorous isopod Idotea baltica. We fed the adult isopods
      with the brown algae Fucus vesiculosus and Pilayella littoralis and juveniles
      with the green alga Cladophora glomerata. By using half-sib families, we were
      able to separate the genetic, environmental and maternal effects on intermolt
      duration and size of the juveniles. The mothers confined to the diet consisting
      of both Fucus and Pilayella grew better and produced larger egg mass than those
      having consumed Fucus alone. Nutrient enhancement of algae did not influence the
      performance of the adult herbivores. However, the juveniles achieved twice the
      weight as well as shorter intermolt duration when consuming nutrient-treated C.
      glomerata. Mother's nutrition, either nutrient enrichment of her food algae or
      diet breadth, did not affect juvenile survival or growth as such, but we found
      evidence that the broader diet consumed by the mother mediated offspring
      performance by further accelerating growth rate of the offspring that fed on
      nutrient-treated alga. Intermolt duration was a highly heritable trait, but size
      showed very low heritability. Instead, maternal effects on size were substantial,
      suggesting that differences among mothers in their egg-provisioning ability
      strongly affect weight gain of their offspring. A high amount of additive genetic
      variance in intermolt duration implies potential for quick evolutionary responses
      in the growth schedule in the face of changes in the selective environment. We
      conclude that eutrophication, in addition to improving growth and reproduction of
      I. baltica by enhancing food quality and by providing opportunity for broader,
      more profitable diets, may act as a selective agent on life-history traits.
      Eutrophication of coastal waters is thus likely to reflect in herbivore density,
      population dynamics and eventually, grazing pressure of littoral macroalgae.

PMID- 15146323
TI  - Environmentally-controlled, density-dependent secondary dispersal in a local
      estuarine crab population.
AB  - The mechanisms driving the pelagic secondary dispersal of aquatic organisms
      following initial settlement to benthic habitats are poorly characterized. We
      examined the physical environmental (wind, diel cycle, tidal phase) and
      biological (ontogenetic, density-dependent) factors that contribute to the
      secondary dispersal of a benthic marine invertebrate, the blue crab (Callinectes
      sapidus) in Pamlico Sound, NC, USA. Field studies conducted in relatively large
      (0.05 km2) seagrass beds determined that secondary dispersal is primarily
      undertaken by the earliest juvenile blue crab instar stages (J1 crabs). These
      crabs emigrated pelagically from seagrass settlement habitats using nighttime
      flood tides during average wind conditions (speed approximately 5 m s-1).
      Moreover, the secondary dispersal of J1 crabs was density-dependent and regulated
      by intra-cohort (J1) crab density in seagrass. Our results suggest that dispersal
      occurs rapidly following settlement, and promotes blue crab metapopulation
      persistence by redistributing juveniles from high-density settlement habitats to
      areas characterized by low postlarval supply. Collectively, these data indicate
      that blue crab secondary dispersal is an active process under behavioral control
      and can alter initial distribution patterns established during settlement. This
      study highlights the necessity of considering secondary dispersal in ecological
      studies to improve our understanding of population dynamics of benthic organisms.

PMID- 15146321
TI  - Protein reabsorption in renal proximal tubule-function and dysfunction in kidney
      pathophysiology.
AB  - The endocytic receptors megalin and cubilin are highly expressed in the early
      parts of the endocytic apparatus of the renal proximal tubule. The two receptors
      appear to be responsible for the tubular clearance of most proteins filtered in
      the glomeruli. Since cubilin is a peripheral membrane protein it has no
      endocytosis signaling sequence. Cubilin binds to megalin and it appears that
      megalin is responsible for internalization of cubilin and its ligands, in
      addition to internalizing its own ligands. The importance of the receptors is
      underscored by the proteinuria observed in megalin-deficient mice, in dogs
      lacking functional cubilin, and in patients with distinct mutations of the
      cubilin gene. In this review we focus on the role of megalin- and cubilin
      mediated endocytosis in renal pathophysiology. Association between disorders
      characterized by tubular proteinuria, such as megaloblastic anemia type-1, Dent
      disease, cystinosis, and Fabry disease and the dysfunction of proximal tubular
      endocytosis is discussed. The correlation between the high capacity of
      endocytosis in the proximal tubule and progressive renal disease in overload
      proteinuria is considered.

PMID- 15146324
TI  - Floral affinity and benefits of dietary mixing with flowers for a polyphagous
      scarab, Popillia japonica Newman.
AB  - Many generalist herbivores, especially adult beetles, are facultative florivores,
      feeding on leaves but readily accepting floral tissues when available. We
      speculated that day-flying beetles with high energetic requirements would benefit
      from dietary mixing with nutrient-rich flower tissues and favor them during
      foraging. We tested that "Floral Affinity Hypothesis" with Popillia japonica, a
      day-active ruteline scarab that feeds intermittently throughout its adult life on
      multiple plant species. In field tests with six species of flowering hosts, far
      more landings occurred on flowers than on foliage for all plants except Hibiscus
      syriacus which bears flowers along the main stem rather than terminally. Trials
      with elevated plants showed that height of the floral display contributes to
      beetles' landing on flowers. Flower petals generally were preferred over leaves
      in laboratory choice tests. Nitrogen and water content were comparable or higher
      in foliage than in petals, but plant sugars were much higher in petals. Longevity
      and fecundity of beetles provided single-plant diets of Hibiscus, Rosa x hybrida,
      or Trifolium flowers for 3 weeks were as high, or higher, than for beetles fed
      foliage of Tilia cordata, a highly suitable resource. As expected, rotating
      flowers or Tilia foliage with marginally suitable Quercus palustris foliage
      enhanced those parameters relative to a diet of Quercus alone, but beetles
      provided high-quality Tilia foliage also benefitted from dietary mixing with
      flowers. Nearly all past dietary mixing studies concerned immature insects, for
      which growth rate is paramount. Opportunistic florivory by adult beetles
      represents a type of dietary mixing wherein the premium may be calorie-rich food
      for fueling flight muscles, with ensuing reproductive benefits.

PMID- 15146325
TI  - Fly parasitoid Megaselia opacicornis uses defensive secretions of the leaf beetle
      Chrysomela lapponica to locate its host.
AB  - Larvae of the leaf beetle Chrysomela lapponica derive a defensive secretion from
      salicyl glucosides found in the host plant Salix borealis. This secretion
      protects beetle larvae from some natural enemies, but does not appear to repel
      parasitoids. We tested the hypothesis that the fly parasitoid Megaselia
      opacicornis (Diptera, Phoridae) uses the larval defensive secretion of Ch.
      lapponica in its search for prey. In the field, nearly 30 times more M.
      opacicornis individuals were caught on leaves coated with sticky resin next to a
      source of secretion than on control leaves. In the laboratory, M. opacicornis
      females laid six times more eggs next to a cotton ball soaked in secretion than
      next to one soaked in water. Fly females also lay more eggs on prey rich in
      larval secretion than on secretion-poor prey. In the field, removal of defensive
      secretion from beetle prepupae resulted in a 7.5-fold reduction of oviposition by
      fly females. Parasitoids were nearly twice as likely to lay eggs on prepupae,
      rich in secretion, as on pupae, which contain little secretion. Fly offspring
      reared from beetle prepupae reached a 21% larger body mass than those reared from
      pupae. Finally, M. opacicornis females avoided host prepupae already parasitized
      by the tachinid fly Cleonice nitidiuscula, which possess little secretion. These
      experiments indicate that host plant-derived defensive secretions are used by
      this parasitoid for host location. Adaptation of parasitoids to use defensive
      secretions of hosts may selectively favor an increase in diet breadth in
      specialist herbivores.

PMID- 15146326
TI  - Plant chemical defense against herbivores and pathogens: generalized defense or
      trade-offs?
AB  - Plants are often attacked by multiple enemies, including pathogens and
      herbivores. While many plant secondary metabolites show specific effects toward
      either pathogens or herbivores, some can affect the performance of both these
      groups of natural enemies and are considered to be "generalized defense
      compounds". We tested whether aucubin and catalpol, two iridoid glycosides
      present in ribwort plantain (Plantago lanceolata), confer in vivo resistance to
      both the generalist insect herbivore Spodoptera exigua and the biotrophic fungal
      pathogen Diaporthe adunca using plants from P. lanceolata lines that had been
      selected for high- and low-leaf iridoid glycoside concentrations for four
      generations. The lines differed approximately three-fold in the levels of these
      compounds. Plants from the high-selection line showed enhanced resistance to both
      S. exigua and D. adunca, as evidenced by a smaller lesion size and a lower fungal
      growth rate and spore production, and a lower larval growth rate and herbivory
      under both choice and no-choice conditions. Gravimetric analysis revealed that
      the iridoid glycosides acted as feeding deterrents to S. exigua, thereby reducing
      its food intake rate, rather than having post-ingestive toxic effects as
      predicted from in vitro effects of hydrolysis products. We suggest that the
      bitter taste of iridoid glycosides deters feeding by S. exigua, whereas the
      hydrolysis products formed after tissue damage following fungal infection mediate
      pathogen resistance. We conclude that iridoid glycosides in P. lanceolata can
      serve as broad-spectrum defenses and that selection for pathogen resistance could
      potentially result in increased resistance to generalist insect herbivores and
      vice versa, resulting in diffuse rather than pairwise coevolution.

PMID- 15146327
TI  - A DNA microarray-based methylation-sensitive (MS)-AFLP hybridization method for
      genetic and epigenetic analyses.
AB  - We previously developed a PCR-based DNA fingerprinting technique named the
      Methylation Sensitive (MS)-AFLP method, which permits comparative genome-wide
      scanning of methylation status with a manageable number of fingerprinting
      experiments. The technique uses the methylation sensitive restriction enzyme NotI
      in the context of the existing Amplified Fragment Length Polymorphism (AFLP)
      method. Here we report the successful conversion of this gel electrophoresis
      based DNA fingerprinting technique into a DNA microarray hybridization technique
      (DNA Microarray MS-AFLP). By performing a total of 30 (15 x 2 reciprocal
      labeling) DNA Microarray MS-AFLP hybridization experiments on genomic DNA from
      two breast and three prostate cancer cell lines in all pairwise combinations, and
      Southern hybridization experiments using more than 100 different probes, we have
      demonstrated that the DNA Microarray MS-AFLP is a reliable method for genetic and
      epigenetic analyses. No statistically significant differences were observed in
      the number of differences between the breast-prostate hybridization experiments
      and the breast-breast or prostate-prostate comparisons.

PMID- 15146328
TI  - Ultrastructure of spermiogenesis and the spermatozoon in Taenia crassiceps
      strobilae WFU strain (Cestoda, Cyclophyllidea, Taeniidae) from golden hamsters.
AB  - Strobilae from Taenia crassiceps (WFU strain) were obtained from outbred hamsters
      (Mesocricetus auratus) by feeding them viable metacestodes maintained by
      intraperitoneal passage in female Balb/c mice. Mature and gravid proglottids from
      strobilae were recovered from hamster intestines and fixed for light and electron
      microscopy. By light microscopy, the expected structure of taeniid proglottids
      was observed. Ultrastructural analysis of ten proglottids showed that testicular
      follicles and vas deferens contained filiform spermatids, with a single axoneme,
      and an elongated helicoidal nucleus inserted between the axoneme and the spiraled
      cortical microtubules. At the apical cone, a single crest-like body was found and
      mature spermatids also exhibited transverse intracytoplasmic walls. The
      morphology and characters of the spermatids in T. crassiceps conform to type III
      spermiogenesis, which has been described in other taeniids.

PMID- 15146330
TI  - L -5-Hydroxytryptophan treatment of sleep terrors in children.
AB  - To test the hypothesis that the administration of L -5-hydroxytryptophan (L -5
      HTP) might exert beneficial effects on sleep terrors, we carried out an open
      pharmacological trial in a group of children with sleep terrors compared to a
      group of children with the same disorder but without L -5-HTP treatment.
      Participants in the trial were 45 children (34 males and 11 females; age range
      3.2-10.6 years), referred to the Sleep Centre of the Department of Developmental
      Neurology and Psychiatry of the University of Rome "La Sapienza", affected by
      sleep terrors. All subjects underwent: (1) complete medical and sleep history;
      (2) complete neurological examination and EEG recording whilst awake and
      sleeping, (3) a structured sleep diary for 2 months, (4) after 1 month, all
      subjects were examined again from the clinical and EEG points of view and (5)
      after 6 months, a structured interview in order to evaluate the clinical outcome.
      After the first visit, L -5-HTP was administered (2 mg/kg per day) at bedtime to
      31 randomly selected patients for a single period of 20 consecutive days. After 1
      month of treatment, 29/31 (93.5%) of patients showed a positive response. In the
      comparison group without drug therapy, after 1 month, the episodes disappeared
      only in four children (28.6%) while ten children (71.4%) showed the persistence
      of episodes with the same frequency as before. After 6 months, 26/31 (83.9%) of
      children treated with L -5HTP were sleep terror-free, while in five children
      (16.1%) sleep terror episodes persisted. Of the children in the comparison group,
      ten (71.4%) continued to show sleep terrors at 6-month follow-up. CONCLUSION: to
      our knowledge, this is the first study demonstrating the efficacy of a new drug
      treatment for sleep terrors. These results confirm our initial hypothesis and
      represent evidence that treatment with L -5-hydroxytryptophan is able to modulate
      the arousal level in children and to induce a long-term improvement of sleep
      terrors.

PMID- 15146329
TI  - Stepwise metastatic human hepatocellular carcinoma cell model system with
      multiple metastatic potentials established through consecutive in vivo selection
      and studies on metastatic characteristics.
AB  - PURPOSE: To establish a "stepwise metastatic human hepatocellular carcinoma (HCC)
      cell model system" for in-depth study of the underlying mechanisms of HCC
      metastasis. METHODS: Using MHCC97- a metastatic human hepatocellular carcinoma
      (HCC) cell line reported in 1999-as the parent cells, we subsequently established
      three cell lines (MHCC97-L, HMCC97-H, and HCCLM3) with increasing spontaneous
      metastatic potential. Now, the fourth cell line with unique multiple metastatic
      characteristics has been established by six rounds of in vivo selection. RESULTS:
      This cell line, designated as HCCLM6, is a polygonal epithelial cell with
      hypotriploid karyotype, the modal chromosomes are 55-58, and marker chromosomal
      abnormalities include i(1) (q10), i(8)(q10), der (4) t(4;8)(q31;q22), i(X)(q10).
      The cell population doubling time was 32 h. Fluorescent PCR showed HBV DNA
      integration in the cellular genome. Thirty-five days after HCCLM6 was injected
      subcutaneously into BALB/c nude mice, prominent lung metastases occurred in 100%
      of the recipient animals. When tumor tissue was orthotopically implanted into the
      liver of nude mouse, widespread loco-regional and pulmonary metastases occurred.
      Inoculation of this cell into the footpad of nude mice also produced 75% regional
      lymph node metastasis. Compared with MHCC97-L which was not metastastatic via
      subcutaneous or footpad inoculation and 40% metastatic via orthotopic
      inoculation, HCCLM6 had increased expression of matrix metalloproteinase (MMP-2
      and MMP-9) and cytokeratin 19 (CK19), and decreased expression of Rb2/p130. The
      establishment of this new cell line has completed our stepwise metastatic HCC
      cell mode system, which was characterized by a similar genetic background but
      with significant differences in spontaneous metastasis behavior. CONCLUSIONS: The
      study supports the theory that cancer metastasis is a highly selective dynamic
      process and the cell model system could be a useful platform for the study of HCC
      metastasis.

PMID- 15146333
TI  - Bipolar disorder--a seriously underestimated health burden.

PMID- 15146331
TI  - Suppression subtractive hybridization-mediated transcriptome analysis from
      multiple tissues of aspen (Populus tremuloides) altered in phenylpropanoid
      metabolism.
AB  - A PCR-based suppression subtractive hybridization (SSH) technique was used to
      identify differentially expressed genes in developing tissues of control and
      transgenic aspen (Populus tremuloides Michx.) with down-regulated 4CL1 (4
      coumarate:coenzyme A ligase) expression and enhanced growth. A total of 11,308
      expressed sequence tags (ESTs) representing 5,028 non-redundant transcripts
      encoding 4,224 unique proteins was obtained from shoot apex, young stem, young
      leaf and root tip SSH libraries. Putative functions can be assigned to 60% of
      these transcripts. Approximately 14% of the ESTs are not represented among the
      111,000 entries already present in Populus EST databases. In general, ESTs of the
      metabolism class occurred at a higher frequency in control- than transgenic
      enriched libraries of all tissues, whereas protein synthesis and protein fate
      ESTs were over-represented in meristematic tissues of transgenics where 4CL1 was
      relatively strongly suppressed. Among all tissues, leaves yielded the highest
      percentage of ESTs with either unknown protein function or insignificant
      similarity to other protein/DNA/EST sequences in existing databases. Of
      particular interest was a large number of ESTs (16%) associated with signal
      transduction in transgenic leaves. Among these were several leucine-rich-repeat
      receptor-like protein kinases with markedly elevated expression in transgenic
      leaves. We also identified homologs of transposable elements that were up
      regulated in transgenic tissues, providing the first experimental data for active
      expression of DNA mobile elements in long-lived tree species.

PMID- 15146332
TI  - Three subsequent infanticides covered up as SIDS.
AB  - Within a period of 9 years a young woman lost 3 daughters during infancy and each
      time death was attributed to the sudden infant death syndrome. The children had
      different fathers and died at the ages of 11 weeks, 7 weeks and 2 weeks,
      respectively. A fourth daughter survived and lives separated from the mother
      together with her father and is healthy. At autopsy the last of the three
      deceased infants did not reveal any pre-existing pathological organ findings,
      except for acute pulmonary emphysema and extensive intra-alveolar bleeding. As a
      consequence the strong suspicion of mechanical suffocation arose. Subsequent
      police investigations produced incriminating clues that the first two children
      had also been suffocated. On confrontation with the autopsy findings and
      investigation results, the woman confessed that she herself had killed the first
      two infants by pressing a cushion on their faces. In the case of the third death
      the baby had been smothered by the child's father who in agreement with the
      mother put a plastic film on mouth and nostrils.

PMID- 15146334
TI  - State- and trait-related deficits in sustained attention in bipolar disorder.
AB  - Investigation of neuropsychological functioning in bipolar disorder provides a
      potential link from the prominent cognitive symptoms of the disorder to the
      underlying neural mechanisms. Continuous performance measures of sustained
      attention have yielded consistent findings in bipolar disorder patients. There
      are impairments that appear to be both state- and trait-related. Impaired target
      detection may represent one of the most sensitive markers of illness course in
      bipolardisorder. It is unrelated to residual mood symptomatology and medication
      status, and is present in patients with good functional recovery. The impairment
      in target detection is exacerbated in the manic state, and is accompanied by an
      increased rate of false responding. Sustained attention deficit is present early
      in the course of the disorder, but becomes more pronounced with repeated
      episodes. This cognitive profile, of an early-onset, state-modulated, trait
      marker, is distinct from the profile of attentional disruption seen in
      schizophrenia or unipolar depression. The state- and trait-related impairments
      may be differentially associated with the ascending dopamine and noradrenaline
      projections.

PMID- 15146335
TI  - Is depressive mixed state a transition between depression and hypomania?
AB  - BACKGROUND: Depressive mixed states (DMX), described systematically by Kraepelin,
      have recently been found common among depressed outpatients, with possible
      important impact on treatment. Study aim was to find if DMX in bipolar II
      disorder was often a transition period between depression and hypomania, as
      suggested by Kraepelin. METHODS: 194 consecutive bipolar II major depressive
      episode (MDE) outpatients were interviewed with the Structured Clinical Interview
      for DSM-IV. Hypomanic symptoms during the index MDE were systematically assessed.
      DMX was defined as a MDE plus > 2 hypomanic symptoms appearing during the MDE
      (not before it), following Akiskal and Benazzi (2003). History of depression
      hypomania cycles and vice versa (without symptom-free intervals) was assessed. If
      DMX were a transition period, cycles should have been more common in bipolar II
      with DMX than in bipolar II without DMX. To test if there were differences
      between DMX with history of cycles and DMX without history of cycles, the two
      subgroups were compared on many clinical, family history, and temperamental
      variables. To test if there were differences between bipolar II with DMX and
      bipolar II without DMX, comparisons between the two subgroups were done on
      variables often reported to be typically found in bipolar disorders and to be
      diagnostic validators (young onset, many recurrences, atypical features of
      depression, bipolar family history, temperamental mood lability, gender).
      RESULTS: DMX was present in 70.1%, and history of cycles in 79.8%. In bipolar II
      without index DMX (n = 58) history of cycles was present in 86.2%; in bipolar
      with index DMX (n = 136) history of cycles was present in 77.2% (p = 0.175). DMX
      with cycles was not significantly different from DMX without cycles on all study
      variables (apart from agitation). Bipolar II with index DMX, versus bipolar II
      MDE without index DMX, had significantly more depressions with atypical features,
      temperamental mood lability, and more females, while age of onset, recurrences,
      and bipolar family history were not significantly different. LIMITATIONS: Single
      interviewer, cross-sectional assessment. CONCLUSIONS: Findings do not support
      Kraepelin's view of DMX as a transition period between depression and hypomania,
      and a distinction between DMX with and without cycles. Findings only partly
      support DMX as a distinct subtype of bipolar II, which seems to require
      temperamental mood lability for its onset during a bipolar II MDE.

PMID- 15146336
TI  - Affective and schizoaffective mixed states.
AB  - Although both DSM-IV and ICD-10 define schizoaffective mixed states, they have
      not received much attention-neither in the clinical nor in research context. We
      present preliminary results of a prospective study of bipolar affective (n = 100)
      and bipolar schizoaffective (n = 177) patients. 25% of the bipolar affective and
      32% of the bipolar schizoaffective patients had at least one (schizo)mixed
      episode during the illness course. Nevertheless, (schizo)mixed episodes were rare
      only 5.6% of all episodes. There was a trend that patients with (schizo)mixed
      episodes were more often women and exhibited more disability (reflected by higher
      rates of disability payments). Nevertheless, these differences failed to reach
      significance. Overall, schizo-mixed episodes are as frequent as "pure" affective
      mixed episodes. They might be linked to a less favourable course. Nevertheless,
      while their diagnostic criteria are problematic, they are systematically
      underdiagnosed.

PMID- 15146338
TI  - Psychological treatment for bipolar disorders--a review of randomised controlled
      trials.
AB  - The increased acceptance of stress-vulnerability models of severe mental
      disorders and of brief evidence-based psychological treatments in their treatment
      has finally led to increased interest in the role of psychotherapies in bipolar
      disorders. This paper reviews the results from randomised controlled trials of
      psychological therapies as an adjunct to standard medications. The evidence
      suggests that the addition of a psychological therapy may significantly reduce
      symptoms, enhance social adjustment and functioning, and reduce relapses and
      hospitalisations in patients with bipolar disorder. However, the methodological
      problems in the published randomised controlled trials and the heterogeneity in
      the outcomes achieved (some therapies reduce manic but not depressive relapses,
      others have the opposite effect) suggests that further studies are required to
      fully establish the place of these approaches in day to day practice.

PMID- 15146337
TI  - Is bipolar I disorder heterogeneous?
AB  - OBJECTIVES: The question whether bipolar I disorder should be subdivided into a
      preponderantly manic group (M) with no depression or only mild depression (Md)
      and a nuclear manic-depressive group (MD) has been rarely studied although the
      problem was raised more than 50 years ago. This paper seeks to elucidate this
      question by contributing further data. METHODS: 406 patients with mood disorders
      hospitalised at some time during the period 1959-1963 were followed-up every five
      years until 1985; mortality data were collected up to 1997. Data on episodes,
      outcome, suicides and attempted suicides, alcohol and substance abuse/dependence
      and long-term medication, as well as on personality (melancholic and manic type)
      were collected. Major mood disorders were subclassified according to their
      hospitalisation for depression (D) and/or mania (M). RESULTS: 30 manic patients
      (M/Md), 130 bipolar I (MD), 60 bipolar II patients (Dm) and 186 major depressive
      patients (D) were compared. The manic group differed from the bipolar I group in
      several variables: better school achievement, milder course of the illness (fewer
      recurrences), significantly less suicidality and a trend to less chronicity and
      more recovery. Manic patients required less long-term medication than bipolars
      and they differed in personality types from bipolars, the personality of manic
      patients being more often of the manic rather than the melancholic type, they
      were also more aggressive than bipolars. The family history data showed that the
      overall morbidity risk of first degree relatives of manic patients was
      significantly lower than that of bipolar patients. CONCLUSIONS: In accord with
      several other studies our data point to the existence of a more manic (M/Md)
      group of bipolar subjects. The diagnosis predicts a better course, lower
      suicidality and fewer and different treatment needs than does nuclear bipolar I
      (MD) disorder. The M/Md groups, as clinically interesting subgroups of the mood
      spectrum, should become a target of further research.

PMID- 15146339
TI  - Should combined pharmaco- and psychotherapy be offered to depressed patients? A
      qualitative review of randomized clinical trials from the 1990s.
AB  - Focusing on recent publications from the 1990s, this article qualitatively
      reviews the comparative efficacy of the combination of pharmaco- and
      psychotherapy (COMBI) vs either modality alone. There is only a weak empirical
      basis recommending the routine use of both psychotherapy and pharmacotherapy in
      acute treatment of Major Depressive Disorders (MDD). Concerning long-term
      treatment of MDD patients, the methodologically sophisticated study from Frank et
      al. shows that a COMBI is superior to interpersonal psychotherapy but not
      superior to medication alone. However, certain subgroups of patients might
      benefit substantially from COMBI compared to both psychotherapy and
      pharmacotherapy alone: 1) acute and long-term treatment of more severe forms of
      chronic depression, and 2) long-term treatment of older MDD patients. Compared to
      psychotherapy alone, severely depressed MDD patients profit more and faster when
      treated with combined psycho-pharmacotherapy.

PMID- 15146340
TI  - Non-neuroleptic approaches to treating negative symptoms in schizophrenia.
AB  - The novel/atypical neuroleptics have proven to be effective in treating negative
      symptoms but although clinical experience appears to show that they have
      advantages over the traditional neuroleptics in treating negative symptoms,
      superiority has not always been statistically confirmed and the treatment results
      in individual patients in everyday clinical practice are often not satisfying.
      Therefore other drug treatment options also have to be carefully considered. This
      paper presents a systematic review of non-neuroleptic drug treatments for
      negative symptoms in schizophrenia, based on MEDLINE searches in the databases
      from 1995 to September 2002 to identify pertinent clinical trials. Relevant
      literature was also found in the reference lists of papers identified by the
      MEDLINE searches. Most of the alternatives to neuroleptics have only been
      investigated as add-on therapies and not as monotherapies. The SSRIs seem to have
      a certain place in the treatment of negative symptoms. Anticonvulsants,
      oestrogens and glutamatergic drugs can currently only be seen as experimental
      drugs and require further empirical evaluation.

PMID- 15146341
TI  - Early detection and secondary prevention of psychosis: facts and visions.
AB  - As effective and practical approaches to primary and universal prevention of
      psychosis are lacking, intervention efforts are targeted at the early stages of
      schizophrenia to prevent (by way of secondary prevention) or postpone psychosis
      onset, reduce severity of illness or at least ameliorate the social consequences
      involved. Early intervention requires early detection and early recognition
      (diagnosis) of persons at risk and early prediction of psychosis. Within the
      German Research Network on Schizophrenia (GRNS) awareness programmes are being
      carried out in several German cities, and these efforts are already improving
      utilisation of early-recognition and early-prediction services by at risk
      persons. The empirical basis of developing a two-step early-recognition inventory
      and strategies of application will be discussed. This instrument is supplemented
      by a set of cognitive tests, prospectively validated in the GRNS. Results from
      preliminary analysis of data covering a two-year period demonstrate that the
      inventory and the cognitive tests are readily accepted. When used for screening
      in non-specialist settings and at the next level, i. e. at early-recognition
      centres, they seem to permit identification of at-risk persons. Early
      intervention is being tested 1) in a randomised controlled multi-centre trial
      consisting of a specially developed cognitive-behavioural therapy in the early
      (prepsychotic) prodromal state and 2) on additional treatment with appropriate
      doses of amisulpride in the late prodromal (early psychotic) state. Preliminary
      data from Study 1 covering 16.3 months show significantly fewer transitions to
      psychosis and from Study 2 reduced positive and negative symptoms and improved
      global functioning compared with controls who had received normal clinical
      treatment. As a result, both the early-recognition inventory plus cognitive tests
      and the two therapy strategies are feasible. We hope that the favourable trend
      indicated by the preliminary data will be confirmed in the final analysis planned
      for 2005 and the objective of implementing effective and practical secondary
      prevention of psychosis and its consequences will be attained.

PMID- 15146345
TI  - Prenatal diagnosis of Pompe disease by electron microscopy.
AB  - INTRODUCTION: Pompe disease is one of the lysosomal storage disorders caused by
      alpha-glucosidase deficiency. The disease is characterized by accumulation of
      glycogen in the lysosome. The accumulation has unique ultrastructural features,
      which enable a prenatal diagnosis possible by electron microscopy. MATERIALS AND
      METHODS: A prenatal diagnosis of Pompe disease by electron microscopic study of
      chorionic villus biopsies is described in a fetus of a mother whose previous
      child had died of the disease. RESULTS: Electron microscopy revealed fibrocytes
      with typical vacuoles filled with glycogen. A prenatal diagnosis of Pompe disease
      was made and subsequently confirmed by the autopsy study of the abortus.
      CONCLUSION: We report the usefulness of electron microscopy for prenatal
      diagnosis in the first trimester of Pompe disease.

PMID- 15146342
TI  - Pharmacological long-term treatment strategies in first episode schizophrenia-
      study design and preliminary results of an ongoing RCT within the German Research
      Network on Schizophrenia.
AB  - In first-episode schizophrenia the advantage of new atypical neuroleptics
      compared to low-dose haloperidol as well as the indicated duration of neuroleptic
      maintenance treatment has still to be based on empirical evidence. Accordingly, a
      multi-center study on the optimization of acute and long-term treatment in first
      episode schizophrenia is currently being carried out as part of the German
      Research Network on Schizophrenia. This paper reports on the design, methods and
      preliminary results of the two-year randomized double-blind study comparing
      risperidone and low-dose haloperidol within the framework of psychological
      interventions. In the second treatment year, relapse rates under continued
      neuroleptic treatment are compared with those under stepwise drug withdrawal
      substituting instead prodrome-based early intervention (intermittent treatment).
      As to the results, by November 2003 142 first episode patients (ICD-10 F20) have
      been included in the long-term study. One-year relapse rates were very low (3.8
      %). On average, symptoms as well as drug side-effects decreased steadily under
      maintenance treatment. Although compliance on average was high, about 60% of the
      patients dropped out during the first study year. More pronounced
      psychopathology, (neurological) side-effects, lower compliance at study entry and
      absence of psychological treatment seemed to enhance the risk for drop-out. In
      conclusion, treatment in first episode schizophrenia is effective under both
      (further on blinded) neuroleptics; however these patients are at high risk for
      treatment drop-out. This emphasizes the need for a special support program.

PMID- 15146347
TI  - Risk factors in the primary management of anorectal malformations in Northern
      India.
AB  - The purpose of this study was to determine the major factors influencing the
      survival of babies with anorectal malformation (ARM) during the primary
      management in the neonatal period in a tertiary referral center. The outcome of
      125 neonates with ARM, treated in a single hospital during a 2-year period, was
      analyzed retrospectively with particular reference to birth weight, time of
      arrival, and the type of ARM, including pouch colon and major associated
      anomalies, to see whether any of them had a significant effect on initial
      survival. High ARM (HARM) was present in 75, low ARM (LARM) in 36, and pouch
      colon in 14 babies. There were a total of 28 deaths (22%). In babies with
      isolated HARM weighing >2.5 kg and brought to the hospital within the first 48 h
      of life, the survival was 100%, which dropped to 80% when brought later than 48
      h. Of the babies with birth weight <2.5 kg and isolated HARM but who were brought
      to the hospital within the first 48 h of life, 80% survived, whereas of those
      reaching the hospital after 48 h, only 55% survived. Two babies with pouch colon
      and two of the four babies with LARM and associated anomalies died. In the HARM
      group, of the 31 babies with major associated anomalies, only 37% with birth
      weight <2.5 kg and 58% with birth weight >2.5 kg survived. Low birth weight,
      major associated anomalies, and delay in referral were the three important
      factors that influenced the outcomes of babies with ARM during the neonatal
      period.

PMID- 15146346
TI  - Microtubule-associated protein-2 immunoreactivity: a useful tool in the
      differential diagnosis of low-grade neuroepithelial tumors.
AB  - Complex and variable morphological phenotypes pose a major challenge to the
      histopathological classification of neuroepithelial tumors. This applies in
      particular for low-grade gliomas and glio-neuronal tumors. Recently, we and
      others have identified microtubule-associated protein-2 (MAP2) as an
      immunohistochemical marker expressed in the majority of glial tumors.
      Characteristic cell morphologies can be recognized by MAP2 immunoreactivity in
      different glioma entities, i.e., process sparse oligodendroglial versus densely
      ramified astrocytic elements. Here, we describe MAP2-immunoreactivity patterns in
      a large series of various neuroepithelial tumors and related neoplasms (n = 960).
      Immunohistochemical analysis led to the following conclusions: (1) specific
      pattern of MAP2-positive tumor cells can be identified in 95% of glial neoplasms;
      (2) ependymal tumors do not express MAP2 in their rosette-forming cell component;
      (3) tumors of the pineal gland as well as malignant embryonic tumors are also
      characterized by abundant MAP2 immunoreactivity; (4) virtually no MAP2 expression
      can be observed in the neoplastic glial component of glio-neuronal tumors, i.e.
      gangliogliomas; (5) malignant glial tumor variants (WHO grade III or IV) exhibit
      different and less specific MAP2 staining patterns compared to their benign
      counterparts (WHO grade I or II); (6) with the exception of melanomas and small
      cell lung cancers, MAP2 expression is very rare in metastatic and non
      neuroepithelial tumors; (7) glial MAP2 expression was not detected in 56 non
      neoplastic lesions. These data point towards MAP2 as valuable diagnostic tool for
      pattern recognition and differential diagnosis of low-grade neuroepithelial
      tumors.

PMID- 15146348
TI  - Comparative physiology and molecular analysis of carbonic anhydrase from the red
      blood cells of teleost fish.
AB  - This study investigates the early evolution of vertebrate red blood cell (rbc)
      carbonic anhydrase (CA) by examining the physiological and molecular properties
      of rbc CA in teleost fish. When representatives of four different families of
      teleosts were compared, it was found that differences in overall rbc CA activity
      were due to different concentrations of CA, rather than differences in the
      enzyme's kinetic properties. Additional molecular analysis of CA from the rbcs of
      rainbow trout provided further evidence that critical elements of the enzyme,
      such as the active site, have been highly conserved during vertebrate evolution.
      The active site of the trout CA differed from that of gar rbc CA at only two
      amino acid positions. The rainbow trout rbc CA sequence also showed high sequence
      homology with CA sequences from other fish tissues, and fits into an emerging
      group of fish CAs that are basal to mammalian CA I, II and III. Northern blot
      analysis of the tissue expression of the sequenced CA indicated that it is
      primarily found in the rbcs, but high amounts of cytosolic CA activity were also
      found in the gill, suggesting the presence of other cytosolic CA isozymes in this
      species.

PMID- 15146349
TI  - [The combination of eye muscle surgery with other interventions on or in the
      eye].
AB  - Strabismus and motility disorders of the eye can be linked in many different ways
      to intraocular diseases and disorders of the lid and orbit. Different functional
      aspects have to be considered before performing combined eye muscle and
      intraocular or adnexal surgery. This allows to avoid unnecessary operations, to
      choose the right dosage of the operation, to limit the risk of diplopia, and
      finally to achieve a satisfying result for the patient.

PMID- 15146350
TI  - The epithelial sodium channel: from molecule to disease.
AB  - Genetic analysis has demonstrated that Na absorption in the aldosterone-sensitive
      distal nephron (ASDN) critically determines extracellular blood volume and blood
      pressure variations. The epithelial sodium channel (ENaC) represents the main
      transport pathway for Na+ absorption in the ASDN, in particular in the connecting
      tubule (CNT), which shows the highest capacity for ENaC-mediated Na+ absorption.
      Gain-of-function mutations of ENaC causing hypertension target an intracellular
      proline-rich sequence involved in the control of ENaC activity at the cell
      surface. In animal models, these ENaC mutations exacerbate Na+ transport in
      response to aldosterone, an effect that likely plays an important role in the
      development of volume expansion and hypertension. Recent studies of the
      functional consequences of mutations in genes controlling Na+ absorption in the
      ASDN provide a new understanding of the molecular and cellular mechanisms
      underlying the pathogenesis of salt-sensitive hypertension.

PMID- 15146351
TI  - Management of the entered frontal sinus.
AB  - The opening of the frontal sinus is a common occurrence in surgical practice. It
      may involve many surgical disciplines. The complications that may derive from
      incorrect treatment of an opened frontal sinus are potentially fatal.
      Unfortunately, the treatment of patients with injured frontal sinus is not
      uniform and standardized. Here, we describe our technique of treatment. We
      propose our treatment modality on the basis of our personal experience, which has
      been excellent in the past 20 years, that is from the time of the technique's
      introduction and routine application.

PMID- 15146352
TI  - Economic evaluation of laparoscopic and open inguinal herniorrhaphies: the effect
      of cost-containment measures and internal hospital policy decisions on costs and
      charges.
AB  - BACKGROUND: Totally extraperitoneal (TEP) repairs of inguinal hernias, despite
      having a favorable clinical outcome are often criticized due to higher costs and
      charges associated with this approach. We, therefore, present a comparison of
      direct costs and charges between TEP and open tension-free (OPN) repairs,
      emphasizing the effect of cost-containment measures on the part of surgeons and
      the hospital's charging (rate-setting) policies on these measurements. METHODS:
      Itemized direct costs, charges, and reimbursements were determined for 41 TEP and
      44 OPN unilateral repairs done between January 1997 and December 1999. Multiple
      sensitivity analyses were done to evaluate the effect of cost-containment
      measures and the hospital's rate-setting policies on the differences in costs and
      charges between the two procedures. The hospital's profits were expressed as
      profit-cost ratios. RESULTS: The mean direct cost for a TEP repair was $128.58
      more than the OPN repair ($795.07[+/-65] vs 666.49 [+/-52]). However, mean
      charges and hospital reimbursement were $2,139.80 and $1,679.87, respectively,
      more for the TEP repairs. The profit-cost ratio was significantly higher in the
      TEP group (2.85:1 vs 1.07:1, P<.001). We found that 79.8% of the difference in
      direct costs vs 29% of the difference in charges between the two procedures was
      sensitive to cost-containment measures. Forty-five percent of the difference in
      charges was due to the hospital's nonuniform rate-setting policies. Long-term
      follow-up (38 months) showed no recurrence for either procedure. CONCLUSIONS: The
      direct cost of TEP repairs with the minimal use of disposable instruments in a
      high-volume center is comparable to the OPN repair. However, due to differences
      in the hospital's charging policies, TEP repair would appear to be an expensive
      alternative from the payer's point of view.

PMID- 15146354
TI  - A clinical classification for patients with inguinal hernia.

PMID- 15146353
TI  - Surgical treatment of large incisional hernias with an intraperitoneal Parietex
      Composite mesh: our preliminary experience on 26 cases.
AB  - BACKGROUND: The authors analyse the results of a prospective study on the use of
      a new type of composite mesh, Parietex Composite (PC) (Sofradim, France),
      positioned intraperitoneally in incisional hernias. METHODS: Twenty-six patients
      (9 men, 17 women), aged 51 on average (range 33-79), were treated with this mesh.
      Twenty-four patients underwent open surgery. Indications were: ventral hernias
      that were big, on the border, multirecurrent, or larger than 10 cm with important
      associated pathologies. Only two patients with small hernias were treated
      laparoscopically. RESULTS: The average follow-up of our survey was 15 months
      (range 6-24). All patients underwent ultrasound scans of the abdomen before
      surgery and 6 months after the operation, according to the Sigel technique, in
      order to detect the presence of visceral adhesions to the mesh. In 23 patients
      (88%), the bowel's motions, both spontaneous and induced, were in a normal range.
      We had neither intestinal occlusions nor fistulae. No deaths occurred.
      Postoperative complications were minor: two seromas (8%), one hematoma (4%), two
      parietal suppurations (8%). No mesh was removed. Only one recurrence occurred
      (4%). CONCLUSIONS: Our preliminary experience with PC is so positive that this
      mesh is currently the one of choice in our department when an intraperitoneal
      implant is required.

PMID- 15146356
TI  - [Sonographic diagnosis of stress urinary incontinence in females].

PMID- 15146355
TI  - Hernia repair in the Lombardy region in 2000: preliminary results.
AB  - Hernia repair is the most common surgical procedure in general surgery in Italy
      and in the Lombardy region. In the last decade, the use of mesh, the concept of a
      tension-free technique, and the postoperative rate of recurrences after Bassini
      or Shouldice operations have completely changed the surgical approach to hernia
      repair. For this reason, we sent a questionnaire to 148 surgical departments in
      the Lombardy region to investigate about total hernia operations performed in
      2000 in Lombardy, the surgical approach, the surgical techniques used, the type
      of anesthesia and the hospital stay. One hundred five out of 148 surgical
      departments returned the questionnaire, and we collected information on a total
      of 16,935 surgical operations for hernia: 16,494 were performed using tension
      free techniques. The inguinal anterior approach is the one of choice for primary
      and recurrent inguinal hernia, whereas the open preperitoneal and laparoscopic
      approaches are limited to bilateral and recurrent hernias. The majority of cases
      were treated under locoregional anesthesia and with a hospital stay of two
      nights.

PMID- 15146357
TI  - [Introital and perineal sonography in diagnosing stress urinary incontinence -
      possible clinical applications].
AB  - Urogynecological ultrasound as a part of the diagnostic work-up of stress urinary
      incontinence enables the morphologic and dynamic assessment of the lower urinary
      tract and has replaced radiography in the primary diagnostic work-up of stress
      urinary incontinence. It is possible to classify the sonographically identified
      changes of the endopelvic fascia, whereby any dynamic changes must be interpreted
      in context with the clinical findings. Stress urinary incontinence, besides
      voiding dysfunction, recurrent urinary tract infections and dyspareunia, may be
      associated with urethral diverticula, which can be detected by ultrasound.
      Postoperative voiding problems, de novo urgency or recurrent urinary tract
      infections can be assessed by demonstrating possible causes, such as haematomas,
      overcorrection with postvoid residual, misplacement of the tape at the level of
      the bladder neck or intravesical displacement of suture or tape material.
      Introital and perineal ultrasound might also be used for monitoring the proper
      placement of sutures to reduce postoperative complications.

PMID- 15146358
TI  - Sonographic findings in hepatic involvement of hereditary haemorrhagic
      telangiectasia.
AB  - AIM: Hereditary haemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an
      autosomal-dominant disorder characterised by angiodysplastic lesions
      (telangiectases and arteriovenous malformations) which affect many organs
      including the skin, lungs, gastrointestinal tract, and brain. A broad spectrum of
      vascular and structural changes have been reported. Our objective was to
      systematically examine the prevalence of sonographic findings in hepatic
      involvement in patients with hereditary haemorrhagic telangiectasia (HHT).
      METHODS: We studied 22 consecutive patients with hereditary haemorrhagic
      telangiectasia by ultrasonography in combination with colour-Doppler and pulsed
      wave-Doppler for liver involvement. The clinical diagnosis of HHT was based on
      the Curacon criteria. RESULTS: Sixteen of the 22 patients had signs of hepatic
      involvement including prominent common hepatic artery (14 of 16), dilatation of
      the intrahepatic part of the hepatic arteries (15 of 16) and intrahepatic AV
      shunts (16 of 16). Ectasia of the hepatic vein, fibrotic parenchymal changes,
      left accessory hepatic artery and focal hepatic lesions were found less
      frequently. CONCLUSION: Diagnosis of liver involvement in HHT can be made by
      sonography with colour-Doppler. The main features of this involvement include
      prominent common hepatic artery, dilatation of the intrahepatic part of the
      hepatic arteries and intrahepatic AV-shunts.

PMID- 15146359
TI  - Fetal skeletal deformities - the diagnostic accuracy of prenatal ultrasonography
      and fetal magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of prenatal ultrasonography and
      fetal magnetic resonance imaging (MRI) in fetuses with skeletal deformities (SD).
      METHODS: Fourteen pregnant women of 21 - 34 weeks of gestation whose fetuses had
      SD on prenatal ultrasound (seven fetuses with spina bifida, four with complex
      malformation syndrome, two with scoliosis, and one with chondrodysplasia) were
      additionally investigated by fetal MRI using a 1.5T superconducting system with
      T1-and T2-weighted sequences in three section-planes. Main outcome measures were
      diagnostic accuracy, potential effect on parental counselling and influence on
      perinatal management of the additional investigation with fetal MRI. RESULTS: In
      10 cases ultrasound had a better diagnostic accuracy than MRI concerning the
      diagnosis of SD. In four cases with spina bifida MRI provided additional
      information towards preoperative evaluation for neurosurgery. In five cases
      parental counselling was improved. There was no influence on perinatal
      management. CONCLUSION: MRI may provide additional information to ultrasound scan
      in fetuses with spina bifida and consecutive neurosurgery; in fetuses with other
      skeletal deformities additional information may be expected only in rare cases.

PMID- 15146360
TI  - [Three-dimensional power Doppler ultrasonography (3D-PDU) in fetal diagnosis].
AB  - AIM: 3D power Doppler ultrasonography (3D-PDU) is a new method which allows the
      spatial presentation of fetal vessels in utero. In the presented study we have
      examined the feasibility of this technique in prenatal diagnosis. Aim of our
      pilot study with normal human fetuses was to determine the adjustment of the
      system presets, the optimal insonation planes and the regions of interest.
      MATERIAL AND METHODS: Seven regions of interest were examined in three different
      planes. The 3D volume was acquired by a free hand sweep. The feasibility of the
      method was quantitatively determined for every plane and region. For each of the
      three planes a total of 25 examinations was planned and the successful rate per
      region of interest was then assessed for the total of these 75 examinations. In a
      two year period, a total number of 80 fetuses from 16 to 34 weeks' gestation
      could be enrolled in the study. RESULTS: Best examinations were achieved in the
      vessels of the umbilical cord (successful rate 100 %), followed by the placental
      and abdominal (84 % each), cerebral (80 %), pulmonary (64 %), and renal vessels
      (51 %). The most difficult conditions for examination and the most unreliable
      results were found for the fetal heart with a success rate of only 31 % of the
      cases. Similar to the experience in 2D power Doppler, a plane with blood flow
      towards the transducer was the best insonation plane. CONCLUSIONS: In our study
      we were able to show that a three dimensional demonstration of fetal vessels is
      possible with the system used. The feasibility is limited by fetal movements and
      unfavourable fetal positioning. The possible benefit of the method is to diagnose
      complex fetal vascular malformations in the future.

PMID- 15146361
TI  - Transcranial contrast imaging of cerebral perfusion in stroke patients following
      decompressive craniectomy.
AB  - AIM: Contrast-enhanced transcranial triggered B-mode technology can be used to
      examine cerebral perfusion. However, this technique is still faced with
      methodological problems, especially the difficulty of overcoming the temporal
      bone window. The aim of the present study is to evaluate a deficit in cerebral
      perfusion after administration of the contrast agent SonoVue (TM) in acute stroke
      patients following decompressive craniectomy. METHODS: Ten stroke patients (aged
      39 to 59 years, mean age 57 years), in whom a decompressive craniectomy due to a
      malignant space-occupying infarction or intracerebral haemorrhage was performed,
      were examined with transcranial duplex sonography after application of the
      contrast agent SonoVue (TM). The transcranial examination was performed using
      transient response harmonic grey scale imaging with bolus kinetics based on a
      contrast harmonic imaging software with single-pulse transmission technology. The
      mechanical index was set at 1.0 to 1.1. Triggered images with pulsing intervals
      of 1000 ms were used for the evaluation of time intensity curves in several
      regions of interest. The sonographically imaged areas of hypoperfusion were
      compared with CT or MRI findings. RESULTS: After injection of the contrast agent,
      the perfusion deficit could be detected ipsilaterally according to the affected
      vascular territory in the area of the MCA in 5 patients, in the area of ACA and
      MCA in 2 patients, in the area of the MCA, ACA and PCA in one patient and in the
      area of intracranial haemorrhage in 2 patients. The calculated average peak
      images corresponded precisely with the superimposed CT or MRI images in shape and
      size in all patients. Additionally, it was possible to observe several
      interesting contrast-induced phenomena in the cerebral parenchyma, as well as
      specific transit-time curve characteristics in the perfusion deficit area.
      CONCLUSIONS: Using contrast-enhanced transcranial duplex sonography with
      transient response harmonic imaging, it is possible to depict the perfusion
      deficit in cerebral microcirculation in patients following decompressive
      craniectomy and to obtain new insights into the pathophysiology of the
      hypoperfusion areas. Further studies should be done in stroke patients through
      the intact skull to standardise this method for early diagnosis of acute deficit
      in cerebral perfusion.

PMID- 15146362
TI  - Verification of anomalies of the central nervous system detected by prenatal
      ultrasound.
AB  - OBJECTIVE: The accuracy of fetal ultrasound (US) in diagnosing central nervous
      system (CNS) malformations was assessed with the aim to define in which cases US
      is reliable enough to assist in decisions on medical indication for abortions
      without resorting to magnetic resonance imaging (MRI). DESIGN: Retrospective
      analysis of the course of 69 fetuses with anomalies of the CNS detected on
      prenatal US in a university hospital. SETTING: General Hospital of Vienna,
      University of Vienna, Austria. METHOD: Prenatal US diagnosis was verified by
      postpartal US, MRI or computed tomography (CT) in the live births, and by autopsy
      of the fetus in cases of pregnancy termination. RESULTS: Abortion was induced in
      40 fetuses for anencephaly (n = 4), exencephaly (n = 6), dorsal dysraphism (n =
      6), encephalocele (n = 3), pronounced hydrocephaly (n = 11), holoprosencephaly (n
      = 4), Dandy Walker cyst (n = 5), and 1 complex syndrome - all confirmed on
      autopsy. In 29 live births, hydrocephaly, meningomyelocele, and microcephaly had
      always been correctly identified prenatally. Four Chiari malformations had been
      missed. Agenesis of the corpus callosum had remained unnoticed in 4 out of 14
      cases and been erroneously reported in 5. Diagnostic errors were frequent for
      Dandy-Walker cyst and great cerebellomedullary cistern. CONCLUSION:
      Transabdominal fetal US did not lead to unjustified interventions. Inaccuracy in
      diagnosing abnormalities of the posterior fossa and the median telencephalon as
      well as aetiological clarification of hydrocephalus require additional MRI of the
      fetal CNS in patients selected accordingly.

PMID- 15146364
TI  - Transcutaneous colour Doppler sonography of lung consolidations: review and
      pictorial essay. Part 1: pathophysiologic and colour Doppler sonographic basics
      of pulmonary vascularity.
AB  - Anatomically, the lung is characterised by a dual blood supply. The existence of
      a systemic bronchial arterial supply to the lung in addition to the pulmonary
      arteries was first described by Galen in the second century. From angiographic
      studies it is known that pulmonary lesions of different aetiologies are
      characterised by differences in arterial supply. Colour Doppler sonography makes
      it possible to classify pulmonary arteries by location, flow direction, and
      quantitative spectral curve analysis. This article will review pathophysiological
      and colour Doppler sonographic basics of pulmonary vascularity.

PMID- 15146363
TI  - [DEGUM Level III recommendation for "follow-up" ultrasound examination (= DEGUM
      Level II) in the 11 - 14 week period of pregnancy].

PMID- 15146365
TI  - [Posttraumatic AV fistula in the upper arm region following a foreign body
      injury. Sonographic diagnosis - a case report].
AB  - This paper reports on the sonographic localisation of a metallic foreign body in
      the upper arm region and its topographic anatomic position as well as the
      sonographic diagnosis of an AV fistula due to a lesion of the brachial blood
      vessels. Ultrasonography is the method of choice for the evaluation and diagnosis
      of foreign body injuries and possible subsequent complications.

PMID- 15146366
TI  - Impact of disease activity on thyroid diseases in patients with acromegaly: basal
      evaluation and follow-up.
AB  - In patients with acromegaly, the exact incidence of thyroid disorders is still
      controversial and less is known about the impact of disease activity and
      successful treatment. To address this issue, we investigated 73 acromegalic
      patients (age 55 +/- 13 yr; mean +/- SD) by ultrasonography in comparison to an
      age-matched control group (54 +/- 1 yr) in the same moderate iodine deficient
      area (retrospective study). These non-acromegalic volunteers (n = 199) were
      examined in the same clinic during a thyroid screening test. At the time of
      examination, 52 (71.2 %) of the acromegalic patients were active, 17 (23.3 %)
      were cured, and 4 (5.5 %) were controlled with somatostatin analogues. The
      prevalence of goiter (normal range < 18 ml female, < 25 ml male) was
      significantly higher (82.2 %) in the mixed group of acromegalics (active, well
      controlled, cured; n = 73) and in the active group (90.4 %) than in the control
      group (n = 199, 18.1 %, p < 0.001). Thyroid nodules were found in 63.0 % of the
      mixed group of acromegalics and in 71.2 % of patients with active disease (33.1 %
      in controls, p < 0.001). (99 m)Tc scintigraphy revealed thyroid autonomy in 9/73
      (12.3 %) and cold nodules in 19/73 (26.0 %) patients. Thyroid cancer was
      diagnosed in 4 (5.5 %) of acromegalic patients (3 papillary and 1 follicular
      carcinoma). We found a weak correlation between the disease duration and the
      initial thyroid volume (r = 0.54, p < 0.0056). Thirty-seven newly diagnosed
      acromegalics were followed over a period of 7.3 +/- 4.1 years. 5 (13.5 %) of
      these patients remained active, 8 (21.6 %) were controlled with somatostatin
      analogues, and 24 (64.9 %) were cured. The mean age, sex distribution, disease
      duration, prevalence of TSH-deficiency, and initial thyroid volume (46 +/- 11 ml
      in active, 42 +/- 7 ml in controlled, and 45 +/- 5 ml in cured patients) did not
      differ statistically between the three groups. In patients with active
      acromegaly, thyroid volume increased by 19.5 +/- 8.1 %. In contrast, thyroid
      volume decreased in the group of medically controlled and cured acromegalics (-
      21.5 +/- 7.1 %; p < 0.005 and - 24.2 +/- 5.7 %; p < 0.002, respectively). No
      correlation was found between thyroid volume and TSH levels, levothyroxine and/or
      iodide administration neither in TSH sufficient nor in TSH insufficient patients.
      In conclusion, successful treatment of patients with active acromegaly decreases
      thyroid volume. Cold nodules and thyroid cancer frequently occur in acromegalic
      patients.

PMID- 15146367
TI  - No evidence for autoimmunity as a major cause of the empty sella syndrome.
AB  - OBJECTIVE: The cause of empty sella syndrome (ESS) remains largely unknown. We
      measured eleven organ-specific autoantibodies in serum in order to evaluate
      possible autoimmune components in ESS. PATIENTS: Thirty patients with ESS and 50
      healthy blood donors participated in the study. MEASUREMENTS: Detection of
      pituitary autoantibodies was performed by immunoblotting with human pituitary
      cytosol as antigen. Thyroid peroxidase (TPO) and TSH receptor (TRAK)
      autoantibodies were analysed by radioimmunoassay. The remaining eight
      autoantibodies were detected by in vitro transcription and translation of the
      autoantigens and immunoprecipitation. RESULTS: The majority of the ESS patients
      (18/30) exhibited no immunoreactivity at all. None of the remaining 12 ESS
      patients reacted against more than one autoantigen. No immunoreactivity was found
      more frequently among ESS patients than healthy blood donors. Pituitary
      autoantibodies were not correlated to the ESS patients' pituitary function or
      sellar size, although the results indicated a tendency of increased autoimmunity
      in patients with hypopituitarism and normal sella size respectively. CONCLUSION:
      Detection of autoantibodies is a valuable tool in the diagnostic work-up of
      autoimmune diseases. By analysing a large number of organ-specific autoantibodies
      we found no evidence of ESS being associated with any specific autoimmune
      disease. The pathogenesis of ESS is believed to be heterogeneous and our findings
      suggest autoimmune components to be of minor importance. In some selective cases,
      ESS in combination with hypopituitarism may be the result of an autoimmune
      disease in the pituitary gland but this needs further investigation.

PMID- 15146368
TI  - Applicability of the SHBG androgen sensitivity test in the differential diagnosis
      of 46,XY gonadal dysgenesis, true hermaphroditism, and androgen insensitivity
      syndrome.
AB  - The sex hormone-binding globulin (SHBG) androgen sensitivity test has been used
      as a simple method to assess androgen receptor function in vivo. After a short
      term oral administration of the anabolic-androgenic steroid stanozolol the mean
      nadir serum concentration of SHBG is used as a measure of androgen response. We
      performed this test in order to evaluate its applicability in 16 patients with
      intersexual genital status: eleven with 46,XY gonadal dysgenesis and three with
      true hermaphroditism (group I), and in two patients with androgen insensitivity
      syndrome (AIS, group II). Ten healthy adult volunteers served as controls. In the
      two patients with AIS (group II) we found a diminished decrease of serum SHBG to
      80.1 % and 80.7 %, respectively, indicating slight residual androgen
      responsiveness. In eleven patients of group I who were not on hormone replacement
      therapy, a mean nadir level of 51.7 +/- 8.7 % was found. In the controls the mean
      nadir serum SHBG level was significantly higher (62.7 +/- 5.2 %), probably due to
      interference of endogenous androgens and contraceptive medication with the
      stanozolol-induced SHBG decrease. In three gonadectomised patients who were on
      hormone replacement therapy the initial SHBG concentration was increased (513.5
      +/- 239.1 nmol/l); the mean nadir SHBG concentration of 45.6 +/- 9.8 % of the
      initial level indicates an increased sensitivity of the test in patients in whom
      the counteracting ovarian androgens are absent. Our findings confirm that under
      standard test conditions the SHBG androgen sensitivity test is a simple
      diagnostic tool for the detection of androgen receptor malfunction.

PMID- 15146370
TI  - Anti-diabetic activity and mechanism of action of chromium chloride.
AB  - Though supplementation of chromium has been found to improve deranged
      carbohydrate and lipid metabolism associated with suboptimal chromium intake in
      patients, its usefulness in the treatment of diabetes mellitus of variable
      etiology remains questionable. In the present investigation, the effect of 6 wk
      oral administration of chromium chloride (CC) on the glucose and lipid metabolism
      was studied in streptozotocin (STZ) diabetic and neonatal-STZ (nSTZ) diabetic
      rats. Further, its cellular mechanism was studied using 3T3-L1 adipocyte and
      C2C12 myoblast cell lines. Treatment with CC significantly improved the impaired
      glucose tolerance and insulin sensitivity of both STZ diabetic and nSTZ diabetic
      rats without any change in basal or glucose stimulated insulin response
      indicating insulin-sensitizing action of chromium. CC treatment also
      significantly improved deranged lipid metabolism. CC per se did not produce any
      effect in vitro, however, significantly increased insulin stimulated glucose
      uptake in C2C12 myoblasts and differentiation of 3T3-L1 preadipocytes into mature
      adipocytes supporting the in vivo insulin-sensitizing action of chromium. This
      study shows that CC exhibited significant anti-diabetic potential in chemically
      induced diabetes in rats, the mechanism of which appears to be potentiation of
      insulin actions at the target tissues leading to improved peripheral insulin
      sensitivity.

PMID- 15146369
TI  - Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL
      profile in combined hyperlipidemia with dense LDL.
AB  - INTRODUCTION: The association of elevated plasma triglyceride concentrations,
      decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic
      lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome
      and type 2 diabetes and may be one of the factors responsible for the increased
      risk for coronary artery disease in these patients. The effect of fenofibrate and
      atorvastatin on the LDL subfraction profile in patients with combined
      hyperlipidemia and a preponderance of dLDL was studied in a sequential design.
      METHODS: Six male patients with combined hyperlipidemia and dLDL received 160
      mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all
      patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after
      fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by
      equilibrium density gradient ultracentrifugation. RESULTS: Treatment with
      atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p =
      0.046) (p-values for differences between treatment groups), triglycerides by 32 %
      and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 %
      and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the
      following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 %
      and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028);
      LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040
      kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6
      (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate
      reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS:
      Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative
      effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL
      profile towards medium dense LDL-particles (qualitative effect). Since medium
      dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a
      higher antiatherogenic potential than assessed by the reduction of total LDL
      cholesterol and triglycerides alone.

PMID- 15146371
TI  - The Gly482Ser variant in the peroxisome proliferator-activated receptor gamma
      coactivator-1 is not associated with diabetes-related traits in non-diabetic
      German and Dutch populations.
AB  - The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is
      involved in regulation of fatty acid oxidation, skeletal muscle fiber type
      specificity, and gluconeogenesis. The prevalent Gly482Ser variant in PGC-1 was
      shown to be associated with type 2 diabetes in some but not all studies.
      Moreover, it is unclear whether it influences prediabetic subphenotypes in non
      diabetic populations. We studied the association of this variant with glucose
      tolerance (oral glucose tolerance test), insulin sensitivity (euglycemic
      hyperinsulinemic clamp) of glucose disposal and antilipolysis, insulin secretion
      (hyperglycemic clamp, 10 mM), maximal oxygen consumption (VO(2)max, bicycle
      ergometry), and intramyocellular lipids (magnetic resonance spectroscopy,
      tibialis and soleus muscle) in a normal glucose tolerant German cohort (n = 423)
      and a normal (n = 65) and impaired glucose tolerant (n = 94) cohort from the
      Netherlands. No statistically significant association with an examined phenotype
      was detected in any of the study cohorts. Specifically, VO(2)max and the soleus
      to-tibialis ratio of intramyocellular lipid contents as a surrogate parameter of
      fiber type specificity was not different between the genotype groups. We
      conclude, that the Gly482Ser variant in PGC-1 is not associated with diabetes
      related traits or skeletal muscle fiber type composition in a non-diabetic German
      and Dutch population.

PMID- 15146372
TI  - Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1
      diabetes mellitus.
AB  - The assessment of the postprandial state in diabetes mellitus has gained
      importance due to postprandial hyperglycemia being considered as an independent
      risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular
      dysfunction through the alteration of the nitric oxide/cyclic guanosine
      monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the
      fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6
      years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/-
      2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late
      complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI:
      25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate)
      levels did not differ between the diabetic and control group, cGMP levels were
      found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/-
      0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS)
      was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p =
      0.004). The diabetic subgroup without late complications had significantly higher
      nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6
      vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were
      similar. The control subjects responded to the test meal with an increase in the
      cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic
      group no change was detected. Postprandial nitrite/nitrate levels decreased in
      both groups, they were significantly lower in the diabetic group. There was no
      difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the
      diabetic subgroups. Postprandial glucose levels showed a significant negative
      correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The
      results suggest that in subjects with type 1 diabetes mellitus NO might have an
      impaired ability to induce cGMP production in the fasting state prior to the
      development of late specific complications or microalbuminuria under
      hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere
      with endothelial NO action, as shown by the decreased nitrite/nitrate and
      unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP
      pathway both in the fasting and postprandial state that was shown in patients
      without diabetic complications may be an early sign of hyperglycemia induced
      vascular damage in type 1 diabetes mellitus.

PMID- 15146373
TI  - Prevalence of fungal foot infections in patients with diabetes mellitus type 1 -
      underestimation of moccasin-type tinea.
AB  - In diabetic patients, mycotic infections may increase the risk of developing
      diabetic foot syndrome. However, few data are available on the prevalence of
      fungal foot infections in patients with diabetes. During a conference attended by
      patients with long-term diabetes, 95 individuals with type 1 diabetes mellitus
      (52 men, 43 women, mean disease duration 35.8 years) were examined for fungal
      infections of the feet. As well as frequency of infection and risk profiles, the
      level of patient awareness and preventive measures taken were assessed by means
      of a questionnaire. Clinically, 78 patients (82.1 %) showed probable pedal fungal
      infections, of which 84.6 % (66/78) were mycologically confirmed by direct
      microscopy and/or culture. Skin mycoses were found in 9 patients (toe webs 5,
      soles 4), onychomycosis in 29 patients and simultaneous infection of nails and
      skin in 28 patients (toe webs 8, soles 20). Thirty-seven (47.4 %) of these
      patients had positive cultures, particularly for the dermatophyte Trichophyton
      rubrum (69.2 % of isolates). A significant correlation was found between
      infection and gender (men more frequently affected) and the age of the patients.
      The actual frequency of mycoses was underestimated by the patients. This
      correlated with the assessment of their own knowledge level concerning fungal
      infections: 83.2 % of patients with skin mycoses and 88.4 % of those with
      onychomycosis of the feet felt that they needed more information about their
      disease. Marked mycoses on the soles were often considered to be dry skin by the
      patients. The high number of infections detected is especially remarkable in that
      this group of patients were highly motivated. It therefore appears that diabetics
      require more diagnostic, therapeutic and preventive care in terms of mycotic
      diseases than has been previously thought.

PMID- 15146374
TI  - Inhibition of HMG-CoA reductase with cerivastatin lowers dense low density
      lipoproteins in patients with elevated fasting glucose, impaired glucose
      tolerance and type 2 diabetes mellitus.
AB  - OBJECTIVE: While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      effectively decrease LDL cholesterol, it remains controversial whether these
      agents also lower dense LDL, which are considered particularly atherogenic.
      METHODS: We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in
      69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2
      diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL
      (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double
      blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for
      12 weeks (n = 34) and placebo (n = 35). RESULTS: Cerivastatin significantly
      reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL
      cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001),
      triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05)
      and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered
      apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute
      changes were greatest in dense LDL and the change in dense LDL made the largest
      contribution to the change of total LDL. The change of dense LDL was highly
      correlated with baseline values. There was no consistent relationship between the
      effect of cerivastatin on triglycerides and the decrease of dense LDL.
      CONCLUSIONS: The HMG CoA reductase inhibitor cerivastatin lowers total and LDL
      cholesterol and the concentration of dense LDL in patients with elevated fasting
      glucose, impaired glucose tolerance or type 2 diabetes.

PMID- 15146375
TI  - Early postpartum hyponatremia in a patient with transient Sheehan's syndrome.
AB  - In modern day health care, Sheehan's syndrome is a rare disorder affecting the
      postpartum period. We present a case of a 33-year-old woman with atonic
      hemorrhage developing a transient Sheehan's syndrome associated with hyponatremia
      six days postpartum. Evaluation of cranial computer tomography and magnetic
      resonance imaging of the pituitary demonstrated normal finding. Immediate
      replacement therapy using sodium, chloride, hydrocortisone, fludrocortisone and
      levothyroxine revealed regression of the Sheehan's syndrome to complete recovery.
      The present report shows that Sheehan's syndrome can be associated with
      hyponatremia and illustrates the need to include hyponatremia as an initial
      symptom in the differential diagnosis of Sheehan's syndrome.

PMID- 15146377
TI  - [Liposarcoma of the spermatic cord--report of one new case and review of the
      literature].
AB  - Liposarcoma of the spermatic cord is a rare entity. Although most liposarcomas of
      the spermatic cord are well-differentiated, the propensity for local recurrence
      is high. Preferential treatment of spermatic cord liposarcoma is radical
      orchiectomy with high ligation of the cord. Radiation therapy is recommended in
      addition to surgery in cases with evidence of more aggressive tumour behavior
      (i.e., high-grade tumour, lymphatic invasion, inadequate margin, or recurrence).
      A 39-year-old-male presented with a 4-year history of a mass in the left scrotum.
      Radical orchiectomy was performed. Pathological analysis demonstrated a well
      differentiated liposarcoma with tumour detection in the surgical margin. In view
      of the incomplete surgical removal of the tumour a retroperitoneal reoperation of
      the testicular vessels and vas deferent with R0-resection was conducted. Without
      any postoperative adjuvant therapy in evidence of recurrence or metastasis was
      noted during the 12-month follow-up period. The current literature on management
      of malignant tumours of the spermatic cord is reviewed. Paratesticular
      liposarcomas are most commonly well-differentiated and lipoma-like and have a
      prolonged clinical course. Radical orchiectomy with wide local excision of the
      mass is the recommended therapy, while adjuvant radiotherapy may be considered in
      high-grade tumours and in recurrent liposarcomas. Retroperitoneal lymphadenectomy
      does not offer any additional therapeutic benefit, and the role of chemotherapy
      is not well defined. Regardless of initial therapy, the risk of local recurrence
      always necessitates long-term followup.

PMID- 15146376
TI  - [Immunotherapy of renal cell carcinoma: results from current phase-III-trials].
AB  - Renal cell cancer is still a challenge not only concerning operative techniques
      (nephron-sparing techniques, established minimally-invasive techniques, such as
      laparoscopy, and experimental minimally-invasive techniques, such as
      cryoablation, radiofrequency ablation and others), but also with regard to the
      impact of systemic (immuno)therapy. Today, a therapeutic algorithm according to
      tumor stage can be set up as follows: tumors smaller than 4 cm in diameter (T1a,
      TNM classification 2003) result in disease-free survival of more than 90%. One of
      the main questions is whether to apply elective nephron-sparing techniques. Organ
      confined tumors larger than 4 cm (T1b and T2, TNM classification 2003) have a
      significant risk like locally advanced tumors (T3, TNM classification 2003) and
      represent a challenge for adjuvant strategies ("surgical therapy plus X").
      Primary metastasized kidney cancer are to be treated with "surgical cytoreduction
      plus X" and secondary (metachronous) metastasized tumors confront established and
      new systemic (immuno)therapy. This review presents the results from current phase
      III-trials investigating immunotherapy for renal carcinoma.

PMID- 15146378
TI  - [Carcinoma of the Bellini duct with an unusual clinical picture].
AB  - A 37-year-old male patient presented with a Bellini duct carcinoma, at first as a
      metastatic illness of the paraaortal lymph nodes, without significant radiologic
      signs of a kidney tumor. Cytological diagnostics did not recognize this tumor.
      Macroscopically and microscopically the tumor fulfilled the major and minor
      criteria of Sringly et al., but immunohistochemical findings did not show cell
      affinity for UEA-1, which, according to the literature, typically confirms its
      origin from Bellini ducts. This rare neoplasm, primarily found in a younger
      population, still represents a diagnostic and therapeutical challenge as a result
      of its aggressive clinical course. In our patient, as in the majority of cases
      presented in the literature, tumor prognosis was very poor, in spite of
      aggressive surgical, radium and immune therapy.

PMID- 15146379
TI  - [Primary sarcomatoid carcinoma of the ureter].
AB  - INTRODUCTION: We present a case of unusually rapid tumor progression in a patient
      with primary sarcomatoid carcinoma of the ureter. CASE REPORT: An 82-year-old
      female patient underwent total nephroureterectomy for a ureteral tumor that
      turned out to be a primary sarcomatoid carcinoma of the ureter. After a normal
      postoperative course, the patient developed a metastatic symptomatic that seemed
      to have appeared "like an explosion" on the 33rd p. o. day. She died shortly
      thereafter. CONCLUSION: This is the second case of primary sarcomatoid carcinoma
      of the ureter published in the literature, a rare and aggressive variant of
      urothelial carcinoma with a highly malignant potential. As no effective adjuvant
      treatment has been reported as yet, we recommend mandatory radical excision of
      the sarcomatoid tumor and early postoperative radiation therapy to increase
      survival.

PMID- 15146380
TI  - [Thoracoabdominal resection of retrocrural residual tumors].

PMID- 15146382
TI  - [The issue of HIV/AIDS--present overview and perspectives].
AB  - Many outstanding discoveries accompany the existence of HIV infections.
      International teams of scientists cooperate and in their work they use a great
      many methods from haematology and immunology to methods of molecular biology that
      pass into methods of molecular virology. These, in turn, open new prospects for
      methods of molecular epidemiology. The development of sensitive and specific
      antibody tests made possible the testing of blood intended for transfusions and
      helped map the epidemilogical situation, describe the clinical course of the
      disease and, in particular, diagnose the asymptomaic stage of infection.
      Gradually, the jigsaw puzzle of the pathogenesis of HIV infections was completed.
      The tremendous advances in antiretrovirus treament meant a turning point in the
      mortality and morbidity of HIV infection. Clinical trials of therapeutic vaccines
      are in progress. Yet despite all the advances and prevention efforts the HIV/AIDS
      pandemic continues.

PMID- 15146383
TI  - [Human intestinal spirochetosis].
AB  - A characteristic feature of human intestinal spirochetosis (IS) is the
      colonization of the mucosa of the large intestine with intestinal spirochetes of
      the genus Brachyspira. The joining of the brachyspirae with the apical cellular
      membrane of enterocytes resembles in histological slides a false brush border of
      the intestinal mucosa. Various symptoms related to the involvement of the large
      gut were found with invasive IS. From the cultures of these cases were isolated
      Brachyspira aalborgii and B. pilosicoli. The frequency of the incidence of
      brachyspirae depended on the socio-economic living conditions of people.
      Colonization of the mucosa of the large gut was found more often in human
      populations in the developing countries; it was fairly rare in countries with
      high hygienic standards. An exception were men of homosexual orienation and
      patients presenting with a HIV infection. Isolation of brachyspirae from the
      faeces and biopsy of the mucosa of the large gut are fairly demanding jobs,
      especially with B. aalborgii. Most documented IS cases of this aetiology were
      diagnosed using immunohistochemical methods and amplification of the genus
      specific region of the gene 16S rRNA. Isolation of B. pilosicoli tends to be
      simpler, it requires anaerobic incubation on selective blood agars for a period
      of 3-6 days at 37 degrees C. When manual haemoculture systems were used, patients
      in a critical state presented a translocation of brachyspirae into blood
      circulation, while automatic systems don't necessarily diagnose spirochetaemia.
      In the management of described cases of invasive IS particularly successful
      proved metronidazole and beta-lactam antibiotics. In isolated B. pilosicoli, in
      vitro tests confirmed sensitivity to metronidazole, ceftriaxone, meropenem,
      tetracycline, moxifloxacine and chloramphenicol. A varying frequency of
      resistance was found with clindamycin and amoxicillin, which how ever was
      efficacious in combination with clavulanic acid.

PMID- 15146384
TI  - [Chronic obstructive pulmonary disease--acute bacterial exacerbations].
AB  - COPD (Chronic obstructive pulmonary disease) belongs to leading causes of
      morbidity and mortality worldwide and results in substantial and everincreasing
      medical, social and economic burden. The same applies to the Czech Republic as
      well. To combat the disease the Global Initiative for Obstructive Lung Disease
      (GOLD) has been founded in collaboration with the World Health Organization
      (WHO). GOLD guideline was published in April 2001 and its Czech version appeared
      in November 2001. The prevention and management of acute exacerbations of COPD
      forms one of the basic chapters of the document. A COPD exacerbation is defined
      as sustained worsening of the patient's condition compared to the stable state
      and beyond normal day-to-day variations that is acute in onset and may warrant
      additional treatment in a patient with known COPD. COPD exacerbations can be
      triggered by both an acute infection (viral or bacterial) and noninfectious cause
      (air pollution events, cold weather, interruption of regular treatment). Accurate
      diagnosis and assessment of the severity of COPD exacrbation, adequate therapy
      including rational application of antibiotics, accurate indication for
      hospitalization and timely admission to an intensive care unit decrease the COPD 
      associated mortality.

PMID- 15146385
TI  - [Antimicrobial prophylaxis in surgery].
AB  - Antimicrobial prophylaxis is an important factor influencing the risk of
      infection at the spot of surgical interventions (SSI). SSIs are the most
      important nosocomial infections of hospitalized surgical patients; they are
      responsible for increases of 10 to 20 % in the total costs of treatment. The
      efficacy of antimicrobial prophylaxis hinges on four basic factors. The first is
      a correctly indicated prophylaxis (in surgical operations with a confirmed
      reduction of SSI risk after prophylaxis and/or in cases of surgical operations,
      where a possible early or organ SSI could have tragic consequences). The second
      factor is the choice of the best possible antimicrobial for a specific
      indication. The third factor is the best possible time for the administration of
      prophylaxis (in most indications at the beginning of anaesthesia). The fourth
      factor influencing the efficacy of prophylaxis is its administration for only the
      absolutely minimum time period necessary (in most indications best is a single
      administration, possibly including a second peroperative ATB dose). The high rate
      of errors in the actual practice of prophylaxis and the confirmed efficacy of
      implementing local recommendations indicate that it is absolutely necessary to
      define national and local recommendations for antimicrobial prophylaxis, to
      ensure that surgeons adhere to these recommendations and to initiate SSI
      surveillance in the Czech Republic.

PMID- 15146386
TI  - [Comparison of the results of in vitro antifungal susceptibility testing using
      the Fungitest kit and the disc diffusion test].
AB  - AIM OF STUDY: Substantial progress has been achieved in the field of in vitro
      antifungal susceptibility testing, including the interpretation of the test
      results towards the clinical practice. Reference methods for antifungal testing
      of yeasts (M27-A) and filamentous fungi (M38-P) are available now. There are
      several alternatives to these standard protocols as the potential candidates for
      a routine laboratory testing of antifungal drugs. The aim of the study is to
      compare the results of antifungal susceptibility testing obtained by Fungitest
      and disk diffusion method. MATERIALS AND METHODS: From 1997 to 2000, 134 strains
      of 16 yeast species from the patients with suspected or proven mycosis were
      evaluated in the mycology laboratory of the Department of Clinical Microbiology,
      Teaching Hospital in Hradec Krlove. All these strains were tested by both disc
      test on Sabouraud agar (pH = 5.6) and Fungitest. The agreement of the results of
      the both methods was determined for all antimycotics and fungal species tested in
      terms of the categories susceptible, intermediate and resistant strain. RESULTS:
      Overall, there was only 60.3 % agreement between these methods for all antifungal
      drugs with the best results for flucytosine (71.4 % agreement), further for
      ketoconazole (66.2 %), amphotericin B (60.2 %), fluconazole (57.9 %),
      itraconazole (52.6 %), and miconazole (50.5 %). The best overall agreement
      between the results for individual species was found with C. lusitaniae (73.9 %),
      C. pelliculosa (73.5 %), C. parapsilosis (71.7 %), and partly with C. albicans
      (67.5 %). The poorest results were associated with fluconazole-resistant yeasts
      Saccharomyces cerevisiae (30.0 %), C. krusei (32.5 %) and C. glabrata (47.7 %).
      Regressive analysis revealed a relative close relationship between the results of
      these methods for miconazole (R = 0.49, P < 0.001), fluconazole (R = 0.45, P <
      0.001), itraconazole (R = 0.42, P < 0.001) and flucytosine (R= 0.37, P < 0.001),
      but not for amphotericin B (R = 0.10) and ketoconazole (R = 0.16). CONCLUSION:
      The comparison of the results of the disk test and Fungitest showed some
      discrepancies which were dependent on an antifungal drug, a yeast species and the
      test conditions. Sabouraud agar and the criteria for interpretation of the
      results of the disk test seemed to be main sources of the disagreement. A
      modified Mueller-Hinton agar (2 % glucose, methylene blue) as a recommended test
      medium in a proposed agar diffusion method M44-P is the way to the improvement of
      standardization and reproducibility of the test.

PMID- 15146387
TI  - [Monitoring the occurrence of fungi in the air and environment at the Hemato
      Oncology Clinic of the Faculty Hospital in Brno-Bohunice].
AB  - OBJECTIVE: The air can be one of the ways of transmission of fungal infections in
      hospital environment. This is why we examined the occurence of fungi in the air
      of units where patients with hemato-oncology disorders, naturally predisposed to
      fungal infections, are hospitalized. MATERIALS AND METHODS: We performed the
      search at four sampling sites with different grade of reverse isolation. (unit
      for allogeneis transplantation, unit for autologous transplantation, intensive
      care unit and standard three-bed room. Air samples were collected by a special
      instrument for aeroscopic sampling (Biotest RCS Plus) during two consecutive
      periods in 2002, in summer (June - July) and in fall (November - December). and
      compared with each other. RESULTS: Forty-four samples of air were collected,
      which yielded 147 fungal isolates, representing 41 genera. The growth of fungi
      was recorded in 34 samples of air (77.3 %), 10 samples were free of fungi. Yeasts
      were not taken into consideration in this study. The isolates belonged mostly to
      the genera Cladosporium (33,9 %), Penicillium (23,9 %), Aspergillus (12,8 %),
      Acremonium (5,6 %) and Alternaria (5,6 %), the other genera represented 18,2 %
      altogether. CONCLUSION: Increasing occurence of fungi was found at the unit for
      autologous transplantation and in the standard room. The results led to
      reconsideration of the daily regime and of environmental factors in both units
      and relevant preventive measures were proposed.

PMID- 15146388
TI  - [Author's reply to the discussion on the article by Ondrejkova A. et. al:
      Transmission of lyssavirus infections from bats to humans].

PMID- 15146389
TI  - A HOX gene mutation in a family with isolated congenital vertical talus and
      Charcot-Marie-Tooth disease.
AB  - Congenital vertical talus (CVT), also known as "rocker-bottom foot" deformity, is
      a dislocation of the talonavicular joint, with rigid dorsal dislocation of the
      navicular over the neck of the talus. This condition is usually associated with
      multiple other congenital deformities and only rarely is an isolated deformity.
      The reported familial cases are consistent with an autosomal dominant mode of
      inheritance with incomplete penetrance. In contrast, Charcot-Marie-Tooth disease
      (CMT) is thought to be a completely distinct heterogeneous group of disorders,
      with foot abnormalities that typically develop a high-arched "claw foot"
      appearance later in life. In the present study, DNA was isolated from 36 members
      of a single upstate (northern) New York white family of Italian descent in which
      both CVT and CMT were segregating. Whole-genome linkage analysis with Affymetrix
      GeneChip Mapping 10K Array defined a 7-Mb critical region on chromosome 2q31,
      which led to candidate-gene sequencing of six HOX genes and detection of a single
      missense mutation, M319K (956T-->A), in the HOXD10 gene. In the study family,
      this mutation was fully penetrant and exhibited significant evidence of linkage
      (LOD 6.33; theta =0), and it very likely accounts for both CVT and CMT in
      heterozygotes.

PMID- 15146392
TI  - [Infants' moods and the chronicity of depressive symptoms: the unique creative
      process of being together for good or ill. Part 2: The formation of negative
      moods in infants and children of depressed mothers].
AB  - In this second paper I present data on the effects of maternal depression on
      infant mood. Maternal depression is relatively stable and the infant continuously
      faces an affective climate characterized by negative affects. These negative
      affects disrupt the interactive experience of the infant and the mother. Positive
      affective matching is limited and reparation of mismatching states is infrequent.
      As a consequence infants develop a negative mood that biases their interactions
      with others and further exacerbates their affective problems.

PMID- 15146391
TI  - [The historic evolution and actual status of psychotherapy practice guidelines in
      Germany].
AB  - The directives for psychotherapy, which were established in 1967 for the
      compulsory national health insurance system, had a strong influence on the
      subsequent development of psychotherapy in Germany. This article depicts the
      historic conditions and the general framework of the directives for psychotherapy
      as well as their development in the decades following. Finally, possible future
      perspectives and risks are discussed.

PMID- 15146390
TI  - Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal
      growth and cause acromesomelic dysplasia, type Maroteaux.
AB  - The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B
      [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces
      cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type
      natriuretic peptide (CNP). CNP has previously been implicated in the regulation
      of skeletal growth in transgenic and knockout mice. The autosomal recessive
      skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps
      to an interval that contains NPR2. We sequenced DNA from 21 families affected by
      AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site
      mutations, and 11 missense mutations. Molecular modeling was used to examine the
      putative protein change brought about by each missense mutation. Three missense
      mutations were tested in a functional assay and were found to have markedly
      deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2
      mutations have heights that are below the mean for matched controls. We conclude
      that, although NPR-B is expressed in a number of tissues, its major role is in
      the regulation of skeletal growth.

PMID- 15146393
TI  - [Predictors of successful psychotherapy referral in a psychotherapy outpatient
      clinic and subsequent psychotherapeutic outcome].
AB  - OBJECTIVES: Many patients are referred to psychotherapy by outpatient units of
      psychiatric hospital departments. This study investigates predictors of success
      and outcome of subsequent psychotherapy in this group of patients. METHODS: Two
      years after referral, 140 out of an initial sample of 215 patients of a
      psychotherapy outpatient unit were followed up by means of a telephone interview
      and questionnaires (GHQ, IIP). In addition, their therapists were interviewed.
      RESULTS: 57.1% of the patients actually began psychotherapy; of these, 67.5%
      completed or were continuing the treatment. Predictors of referral success were
      younger age, female gender, higher levels of depression, a less competitive,
      subassertive, nurturant, and expressive personality style, and a preexisting high
      motivation for psychotherapy. In the total sample of 140 patients there was a
      significant improvement of psychopathology (0.54 < d < 0.99), interpersonal
      problems (0.25 < d < 0.33), and subjective experience of symptoms (d = 0.26).
      Patients who began psychotherapy did not show a significantly better outcome
      after two years compared to those who were non-compliant. CONCLUSIONS: Randomized
      controlled studies are not comparable to regular outpatient treatment. Patients
      who did not begin psychotherapy despite referral might have been stabilized by
      the initial brief intervention they received at the psychotherapy outpatient
      unit, and consequently did not feel the need for any additional psychotherapy.
      This group of patients should be identified before being referred and offered a
      short-term psychotherapy at the outpatient unit.

PMID- 15146394
TI  - [Secondary prevention for police officers involved in job-related psychologically
      stressful or traumatic situations].
AB  - OBJECTIVES: Police officers are at high risk of being exposed to psychologically
      straining situations and potentially psychotraumatic experiences. In this
      article, such situations are exemplified and categorized, and the role and
      significance of secondary prevention following traumatic experiences is
      discussed. METHODS: From 1994 to 2003, 649 police officers received secondary
      prevention after being involved in a total of 250 potentially traumatic or
      psychologically stressful incidents. Psychological support was provided by teams
      of specially trained professionals in the acute phase after the incident
      following careful psychological evaluation. In a retrospective evaluation, the
      diagnoses obtained were analyzed with regard to sex and age and correlated with
      the severity of the incident. Three clusters of potentially traumatic situations
      were formed: (1) Employment of fire-arms with danger for the officer, (2)
      Standard situations including violence towards a third party, (3) Suicide or
      attempted suicide of a police officer. RESULTS: Police officers who experienced
      events assigned to cluster (1), comprising situations with considerable traumatic
      potential, had the highest incidence of posttraumatic stress disorder (PTSD) or
      other mental illness. Compared to male officers, females were more often
      diagnosed with other mental illness, whereas males had a higher incidence of
      PTSD. Cluster (2), which comprised situations of an officer's daily professional
      life, was not associated with an increased risk of mental illness. Officers were
      apparently capable of coping with situations considered psychologically straining
      for the general public without detectable evidence of a traumatic reaction. In
      cluster (3), which reflects the most dramatic interference with team relations,
      other forms of mental illness were diagnosed at a higher incidence.

PMID- 15146395
TI  - [Psychotherapy and evidence-based medicine (EBM)--randomized controlled vs.
      naturalistic studies: is there only one gold standard?].
AB  - OBJECTIVES: The present article deals with the question as to which kind of
      evidence is necessary to demonstrate the effectiveness of a psychotherapeutic
      method. RESULTS: The authors point out that randomized controlled studies (RCTs)
      are carried out in standardized laboratory contexts, whereas naturalistic studies
      are based on conditions in the psychotherapeutic practice. Accordingly, RCTs and
      naturalistic studies address different questions of research (laboratory vs.
      field). CONCLUSIONS: This view has several important implications: (1.) RCTs and
      naturalistic studies do not differ concerning their internal and external
      validity. (2.) In principal, naturalistic studies do not provide lower level
      evidence than RCTs. (3.) Evidence from RCTs cannot be transferred to
      psychotherapeutic practice in the field: If a therapy has worked in an RCT, this
      does not necessarily imply that it will work in the field as well. (4.)
      Naturalistic studies provide important evidence for determining the effectiveness
      of a therapy in practice. (5.) The proposed catalogues for levels of evidence
      focus on RCTs. Thus, they cannot be applied to hypotheses on the effectiveness of
      a therapy in the field (naturalistic studies). (6.) It is necessary to define
      separate criteria for levels of evidence of naturalistic studies. In this
      article, criteria and levels of evidence of naturalistic studies are defined. The
      implications of the differentiation of randomized controlled vs. naturalistic
      studies is discussed.

PMID- 15146403
TI  - Reconstituting people or reconstituting work? The conundrum of occupational
      epidemiology.

PMID- 15146404
TI  - Structural progression is also driven by clinical symptoms in patients with
      osteoarthritis.

PMID- 15146405
TI  - Dietary weight loss and exercise for obese adults with knee osteoarthritis:
      modest weight loss targets, mild exercise, modest effects.

PMID- 15146406
TI  - Toward a better understanding of methotrexate.

PMID- 15146407
TI  - Documenting damage progression in a two-year longitudinal study of rheumatoid
      arthritis patients with established disease (the DAMAGE study cohort): is there
      an advantage in the use of magnetic resonance imaging as compared with plain
      radiography?
AB  - OBJECTIVE: In early rheumatoid arthritis (RA), longitudinal studies have
      demonstrated that magnetic resonance imaging (MRI) is more sensitive than
      radiography in demonstrating progressive erosive joint damage. The present study
      evaluated the progression of erosive damage in patients with established RA by
      using limited field of view MRI and comparing the results with those obtained by
      radiography. METHODS: MRI and radiographic studies were available from 47 of 60
      patients enrolled in a 2-year RA observational study. MRI of the
      metacarpophalangeal (MCP) joints was performed at baseline and 2 years later, and
      a single observer scored all of the MR images with the use of an MRI scoring
      method developed by the Outcome Measures in Rheumatology Clinical Trials MRI RA
      study group. MR images from 14 patients were reread by the same observer after 1
      week to assess intraobserver reliability. Radiographs were obtained at baseline
      and at 2 years, and were scored by an observer using the Scott modification of
      the Larsen score. Radiographs from 14 patients were reread after 1 week to assess
      the intraobserver reliability. The smallest detectable difference (SDD) was
      calculated for the MRI scores, the total Larsen scores, and the Larsen scores of
      the dominant-hand MCP joints (MCPs 2-5) for direct comparison with the MRI
      results. RESULTS: The median disease duration was 5.1 years (range 0.5-29 years).
      Evidence of erosion progression was identified by MRI in 30 patients (64%). The
      SDD based on the intraobserver scores was calculated as +/-3.25 units. Using this
      result, 11 patients (23%) showed evidence of erosion progression on MRI that was
      greater than the SDD. The SDD for progression based on the intraobserver total
      Larsen radiographic scores was 0.77 units, and the SDD for the Larsen scores of
      the dominant-hand MCP joints was 1.55 units. On the basis of these results,
      radiographic progression was noted in 19 patients (40%) by the total Larsen score
      and 7 patients (15%) by the dominant-hand MCP Larsen score. The most striking
      finding was that although MRI and radiograph scores identified a similar group of
      patients as having progression of joint damage, the radiographs of both hands
      appeared to be more responsive to change, albeit with the caveat that
      radiographic progression was most marked outside the dominant-hand MCP joints.
      CONCLUSION: There was no clear advantage of MRI with a limited field of view as
      compared with radiographic imaging of both hands in detecting progression of
      joint damage over 2 years in this group of patients with established RA. The
      conclusion drawn from this study is not that radiographs are better than MRI or
      vice versa, but that careful analysis is required to determine the optimal
      imaging method, or combination of imaging methods, for each study population,
      depending on the objective and duration of the study.

PMID- 15146408
TI  - Markers for type II collagen breakdown predict the effect of disease-modifying
      treatment on long-term radiographic progression in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate in a randomized clinical trial setting with an
      aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy
      induced changes in urinary C-terminal crosslinking telopeptide of type I collagen
      (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in
      patients with rheumatoid arthritis (RA). METHODS: Patients had participated in
      the COBRA (Combinatietherapie Bij Reumatoide Artritis) trial comparing aggressive
      step-down combination therapy (the COBRA regimen, including temporary high-dose
      prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild
      monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and
      3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored
      according to the modified Sharp/van der Heijde method (mean of 2 independent
      readers who were aware of the sequence). Individual long-term radiographic
      progression was estimated, using baseline radiographs and all radiographs
      obtained during the followup period, by simple linear regression analysis (curve
      fitting). RESULTS: Both COBRA therapy and SSZ monotherapy produced a significant
      decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was
      amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline
      levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I,
      significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively)
      at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3
      months significantly predicted long-term (5-year) radiographic progression (beta
      = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was
      independent of the change in disease activity and inflammation indices at 3
      months. Patients whose CTX-II levels were normalized (<150 ng/mmoles of urinary
      creatinine) at 3 months had a significantly higher chance of radiographic
      stability (no progression over 5 years) than did patients whose CTX-II levels
      were increased both at baseline and at 3 months (odds ratio 4.5 [95% CI 1.5,
      13]). CONCLUSION: The individual CTX-II response measured after 3 months of
      therapy in patients with active RA who had increased CTX-II levels at baseline
      independently predicts long-term radiographic progression. Urinary CTX-II levels
      may be used as early markers of treatment efficacy in patients with RA.

PMID- 15146409
TI  - Radiographic, clinical, and functional outcomes of treatment with adalimumab (a
      human anti-tumor necrosis factor monoclonal antibody) in patients with active
      rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized,
      placebo-controlled, 52-week trial.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory cytokine
      that mediates inflammatory synovitis and articular matrix degradation in
      rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human
      anti-TNF monoclonal antibody, to inhibit the progression of structural joint
      damage, reduce the signs and symptoms, and improve physical function in patients
      with active RA receiving concomitant treatment with methotrexate (MTX). METHODS:
      In this multicenter, 52-week, double-blind, placebo-controlled study, 619
      patients with active RA who had an inadequate response to MTX were randomized to
      receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20
      mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant
      MTX. The primary efficacy end points were radiographic progression at week 52
      (total Sharp score by a modified method [TSS]), clinical response at week 24
      (improvements of at least 20% in the American College of Rheumatology core
      criteria [ACR20]), and physical function at week 52 (disability index of the
      Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was
      statistically significantly less radiographic progression, as measured by the
      change in TSS, in the patients receiving adalimumab either 40 mg every other week
      (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with
      that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In
      addition, there were statistically significant changes in the components of the
      TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the
      adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus
      30% of patients in the placebo group (P < or = 0.001 for each comparison). At
      week 52, ACR20 responses were achieved by 59% and 55% of patients taking
      adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of
      patients taking placebo (P < or = 0.001 for each comparison). At week 52,
      physical function as measured by the HAQ demonstrated statistically significant
      improvement with adalimumab 40 mg every other week and 20 mg weekly compared with
      placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P
      < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52
      weeks of treatment. Adalimumab was generally well tolerated. Discontinuations
      occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated
      patients. The rate of adverse events (both serious and nonserious) was comparable
      in the adalimumab and placebo groups, although the proportion of patients
      reporting serious infections was higher in patients receiving adalimumab (3.8%)
      than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the
      patients receiving 40 mg every other week. CONCLUSION: In this 52-week trial,
      adalimumab was more effective than placebo at inhibiting the progression of
      structural joint damage, reducing the signs and symptoms, and improving physical
      function in patients with active RA who had demonstrated an incomplete response
      to MTX.

PMID- 15146411
TI  - Midkine, a heparin-binding growth factor, is fundamentally involved in the
      pathogenesis of rheumatoid arthritis.
AB  - OBJECTIVE: Midkine (MK), a heparin-binding growth factor, promotes growth,
      survival, and migration of various cells. The essential role of MK in migration
      of inflammatory cells has been shown using mice deficient in the MK gene (Mdk(-/
      ) mice). We undertook this study to investigate the role of MK in the
      pathogenesis of rheumatoid arthritis (RA). METHODS: MK levels in specimens from
      patients were determined by enzyme-linked immunosorbent assay, and localization
      of MK was revealed by immunohistochemical analysis. Susceptibility to antibody
      induced arthritis was compared between Mdk(-/-) and wild-type (WT) mice.
      Osteoclast differentiation was monitored using macrophage-like cells isolated
      from human synovial tissue and macrophages from mouse bone marrow. RESULTS: MK
      levels in sera and synovial fluid were increased in most RA patients, indicating
      a strong correlation between MK expression and RA. MK was expressed in macrophage
      like cells and fibroblast-like cells in synovial membranes from the patients. In
      antibody-induced arthritis, Mdk(-/-) mice seldom developed the disease, while
      most of the WT mice did. Administration of MK to the Mdk(-/-) mice increased the
      frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to
      the synovial membranes in the disease model was suppressed in the Mdk(-/-) mice.
      Furthermore, MK was found to promote the differentiation of osteoclasts from
      macrophages. CONCLUSION: MK participates in each of the two distinct phases of RA
      development, namely, migration of inflammatory leukocytes and osteoclast
      differentiation, and is a key molecule in the pathogenesis of RA.

PMID- 15146412
TI  - Secretion of oncostatin M by neutrophils in rheumatoid arthritis.
AB  - OBJECTIVE: Neutrophils are known to express and release a large number of
      proinflammatory cytokines when they are stimulated by inflammatory stimuli. The
      objective of this study was to determine whether neutrophils express oncostatin M
      (OSM), a member of the interleukin-6 family of cytokines that has been implicated
      in the pathogenesis of inflammatory joint disease. METHODS: Neutrophils were
      isolated from the blood of healthy volunteer donors and from the blood and
      synovial fluid of patients with rheumatoid arthritis (RA). OSM levels were
      measured in cell extracts and in culture supernatants by Western blotting. Total
      RNA was isolated from control and granulocyte-macrophage colony-stimulating
      factor (GM-CSF)-treated neutrophils, and OSM messenger RNA levels were quantified
      by hybridization of a radiolabeled probe. RESULTS: GM-CSF stimulated a rapid and
      transient expression and release of OSM from blood neutrophils, which was more
      rapid than the expression and release from blood monocytes. A 28-kd protein was
      identified in cell extracts, but an additional 25-kd isoform was detected in
      culture supernatants. Synovial fluid neutrophils could not be stimulated to
      express OSM, but this cytokine was detected in cell-free supernatants at various
      levels. CONCLUSION: Blood neutrophils can be stimulated to express and rapidly
      release large quantities of OSM. We propose that this important cytokine is
      released from neutrophils as they infiltrate rheumatoid joints and, thus,
      contribute to the complex cytokine network that characterizes RA.

PMID- 15146410
TI  - Combination therapy with etanercept and anakinra in the treatment of patients
      with rheumatoid arthritis who have been treated unsuccessfully with methotrexate.
AB  - OBJECTIVE: To determine the potential for additive or synergistic effects of
      combination therapy with the selective anti-tumor necrosis factor alpha agent
      etanercept and the anti-interleukin-1 agent anakinra. METHODS: Two hundred forty
      four patients in whom rheumatoid arthritis (RA) was active despite methotrexate
      therapy were treated with subcutaneous etanercept only (25 mg twice weekly), full
      dosage etanercept (25 mg twice weekly) plus anakinra (100 mg/day), or half-dosage
      etanercept (25 mg once weekly) plus anakinra (100 mg/day) for 6 months in a
      double-blind study at 41 centers in the US. Patients had never previously
      received anticytokine therapy. Patient response was measured with the American
      College of Rheumatology (ACR) core set criteria, a health-related quality-of-life
      questionnaire, and the Disease Activity Score. Safety was assessed by the number
      of adverse events and clinical laboratory values. Plasma concentrations of both
      agents and antibody formation against both agents were also assessed. RESULTS:
      Combination therapy with etanercept plus anakinra provided no treatment benefit
      over etanercept alone, regardless of the regimen, but was associated with an
      increased safety risk. Thirty-one percent of the patients treated with full
      dosage etanercept plus anakinra achieved an ACR 50% response, compared with 41%
      of the patients treated with etanercept only. This result was not statistically
      significant (P = 0.914). The incidence of serious infections (0% for etanercept
      alone, 3.7-7.4% for combination therapy), injection-site reactions, and
      neutropenia was increased with combination therapy. Combination therapy had no
      effect on the pharmacokinetics or immunogenicity of either agent. CONCLUSION:
      Combination therapy with etanercept and anakinra provides no added benefit and an
      increased risk compared with etanercept alone and is not recommended for the
      treatment of patients with RA.

PMID- 15146413
TI  - Macrophage migration inhibitory factor up-regulates the expression of interleukin
      8 messenger RNA in synovial fibroblasts of rheumatoid arthritis patients: common
      transcriptional regulatory mechanism between interleukin-8 and interleukin-1beta.
AB  - OBJECTIVE: Interleukin-8 (IL-8) plays an important role in the migration of
      inflammatory cells into the synovium and joint fluids in rheumatoid arthritis
      (RA). This study was undertaken to investigate the IL-8 inductive activity of the
      macrophage migration inhibitory factor (MIF) in RA synovial fibroblasts. The
      regulatory mechanism of IL-8 was compared with that of IL-1beta. METHODS: MIF
      induced IL-8 and IL-1beta transcriptional activation was studied in RA synovial
      fibroblasts by Northern blot analysis, enzyme-linked immunosorbent assay, and
      electromobility shift assay. The effect of anti-MIF antibody administration on
      murine passive collagen-induced arthritis (CIA) was also evaluated by histologic
      examination and reverse transcriptase-polymerase chain reaction. RESULTS: MIF up
      regulated the IL-8 messenger RNA (mRNA) and protein levels in a dose-dependent
      manner. The IL-8 mRNA up-regulation started 1 hour poststimulation by MIF, and
      reached a maximum level at 6 hours. IL-1beta mRNA was also up-regulated by MIF.
      The mRNA up-regulation of IL-8 and IL-1beta by MIF was inhibited by 2 tyrosine
      kinase inhibitors, a protein kinase C (PKC) inhibitor, an activator protein 1 (AP
      1) inhibitor, and by an NF-kappaB inhibitor. A cAMP-dependent kinase inhibitor
      did not inhibit it. MIF enhanced AP-1 and NF-kappaB binding activities in a dose
      dependent manner. Passive CIA enhanced mRNA levels of macrophage inflammatory
      protein 2 and cytokine-induced neutrophil chemoattractants and, moreover,
      migration and proliferation of inflammatory cells within the synovium, which were
      suppressed by administration of an anti-MIF antibody. CONCLUSION: MIF may play an
      important role in the migration of inflammatory cells into the synovium of
      rheumatoid joints via induction of IL-8. MIF up-regulates IL-8 and IL-1beta mRNA
      via tyrosine kinase-, PKC-, AP-1-, and NF-kappaB-dependent pathways.

PMID- 15146414
TI  - Ribozymes that inhibit the production of matrix metalloproteinase 1 reduce the
      invasiveness of rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVE: To investigate whether retroviral gene transfer of ribozymes targeting
      matrix metalloproteinase 1 (MMP-1) inhibits the production of MMP-1 in rheumatoid
      arthritis synovial fibroblasts (RASFs) and reduces the invasiveness of these
      cells in vivo. METHODS: MMP-1-specific ribozymes (RzMMP-1) were designed and
      cloned into the pLNSX retroviral vector. Cleavage of MMP-1 was determined in
      vitro, and the most effective ribozyme was selected for further investigation.
      RASFs were transduced with replication-deficient viruses carrying RzMMP-1 or with
      empty viruses (mock). Quantitative polymerase chain reaction with cleavage site
      spanning fluorescent probes was used to measure the levels of MMP-1, MMP-9, and
      MMP-13 messenger RNA. In addition, protein levels of MMP-1 in cell culture
      supernatants were determined by enzyme linked immunosorbent assay. The effects of
      stimulation with lipopolysaccharide (LPS) and tumor necrosis factor alpha
      (TNFalpha) on the production of MMP-1 were assessed accordingly. The invasiveness
      of RzMMP-1-transduced, mock-transduced, and untransduced RASFs was analyzed in
      the SCID mouse in vivo model of RA. RESULTS: Transduction of RASFs with RzMMP-1
      significantly decreased the production of MMP-1 in RASFs without affecting other
      MMPs, such as MMP-9 and MMP-13. RzMMP-1 not only reduced the spontaneous
      production of MMP-1, but also prevented the LPS- and TNFalpha-induced increase in
      MMP-1 production. Inhibition of MMP-1 was maintained for at least 2 months and
      was accompanied by a significant reduction of the invasiveness of RASFs in the
      SCID mouse model of RA. CONCLUSION: Intracellular expression of ribozymes
      constitutes a feasible tool for inhibiting the production of matrix-degrading
      enzymes. Inhibition of MMP-1 alone results in a significant reduction of
      cartilage invasion by RASFs.

PMID- 15146415
TI  - Expression of Toll-like receptor 2 on CD16+ blood monocytes and synovial tissue
      macrophages in rheumatoid arthritis.
AB  - OBJECTIVE: CD16 (IgG Fcgamma receptor type IIIA [FcgammaRIIIA])-expressing CD14+
      monocytes express high levels of Toll-like receptor 2 (TLR-2) and are able to
      efficiently produce proinflammatory cytokines such as tumor necrosis factor alpha
      (TNFalpha). To understand the role of CD16 and TLR-2 in monocyte and macrophage
      activation in rheumatoid arthritis (RA), we investigated the expression of TLR-2
      on CD16+ blood monocytes and synovial tissue macrophages and the effect of CD16
      and TLR-2 activation on cytokine production. METHODS: The expression of CD14,
      CD16, TLR-2, and TLR-4 on blood monocytes was measured by flow cytometric
      analysis. CD16 and TLR-2 expression in RA synovial tissue was detected by 2-color
      immunofluorescence labeling. CD16+ mature monocytes were prepared by incubating
      blood monocytes in plastic plates for 24 hours. These adhered monocytes were
      stimulated with lipoteichoic acid (LTA), anti-FcgammaRIII antibody, and Hsp60 for
      5 hours, and culture supernatants were measured for various cytokines by
      immunoassay. The activation of NF-kappaB was detected by electrophoretic mobility
      shift assay. RESULTS: The frequency of CD16+ cells in all blood monocytes was
      significantly increased in patients with RA compared with healthy controls. TLR-2
      was expressed at higher levels on CD16+ monocytes than on CD16- monocytes, while
      TLR-4 was expressed similarly on both monocytes. In RA synovial tissue, CD16+/TLR
      2+ cells were distributed mainly in the lining layer. TLR-2 expression on
      monocytes was enhanced by macrophage colony-stimulating factor (M-CSF) and
      interleukin-10 (IL-10), but was reduced by transforming growth factor beta1,
      while CD16 expression was inducible by these cytokines. Adhered monocytes (
      approximately 50% CD16+) produced TNFalpha, IL-1beta, IL-6, IL-8, IL-12 p40, IL-1
      receptor antagonist, and IL-10 after LTA stimulation. This cytokine response was
      inhibited significantly by anti-TLR-2 antibody and partly by anti-TLR-4 antibody.
      Anti-FcgammaRIII antibody stimulation markedly enhanced the LTA-induced TNFalpha
      response. Hsp60 could stimulate TNFalpha production by adhered monocytes, which
      was inhibited similarly by anti-TLR-2 antibody and anti-TLR-4 antibody. NF-kappaB
      activation in adhered monocytes was induced by LTA, but this NF-kappaB activity
      was not augmented by anti-FcgammaRIII antibody stimulation. CONCLUSION: These
      results suggest that CD16+ monocytes and synovial tissue macrophages with high
      TLR-2 expression may be induced by M-CSF and IL-10, and their production of
      TNFalpha could be simulated by endogenous TLR ligands such as Hsp60 and
      FcgammaRIIIA ligation by small immune complexes in RA joints.

PMID- 15146416
TI  - Expression of interleukin-21 receptor, but not interleukin-21, in synovial
      fibroblasts and synovial macrophages of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the role and expression of the cytokine/receptor pair
      interleukin-21 (IL-21)/IL-21 receptor (IL-21R) in rheumatoid arthritis (RA).
      METHODS: The expression of IL-21R and IL-21 was analyzed by TaqMan real-time
      polymerase chain reaction (PCR) and in situ hybridization of synovial biopsy
      samples from patients with RA and osteoarthritis (OA). Double labeling by
      immunohistochemistry after in situ hybridization was performed with anti-CD68
      antibodies. The expression of IL-21R at the protein level was confirmed by
      Western blotting. Stimulation experiments were performed with recombinant IL
      1beta, tumor necrosis factor alpha (TNFalpha), platelet-derived growth factor
      (PDGF), and transforming growth factor beta (TGFbeta). The role of IL-21R in
      cartilage destruction was analyzed in the SCID mouse coimplantation model of RA.
      RESULTS: IL-21R was found in total RNA extracts and in synovial biopsy samples
      from RA patients, whereas no expression or only minimal expression was seen in
      samples from OA patients. Double labeling indicated that both synovial
      macrophages and synovial fibroblasts expressed IL-21R. Western blotting with anti
      IL-21R antibodies confirmed the expression of IL-21R protein in RA synovial
      fibroblasts (RASFs). Of note, IL-21 was not detectable by real-time PCR and in
      situ hybridization in the same samples in vivo as in vitro. The level of
      expression of IL-21R messenger RNA (mRNA) was not altered by stimulation with IL
      1beta, TNFalpha, PDGF, or TGFbeta. Interestingly, in the SCID mouse
      coimplantation model, RASFs did not maintain their expression of IL-21R at sites
      of invasion into the cartilage. Similarly, IL-21R mRNA was not expressed at sites
      of invasion into cartilage and bone in RA synovium. CONCLUSION: Our data
      demonstrate that IL-21R is expressed in RA synovium by RASFs and synovial
      macrophages. IL-21R is associated with the activated phenotype of RASFs
      independently of the major proinflammatory cytokines IL-1beta and TNFalpha, but
      correlates negatively with the destruction of articular cartilage and bone.

PMID- 15146417
TI  - Progression of radiographic hip osteoarthritis over eight years in a community
      sample of elderly white women.
AB  - OBJECTIVE: To describe progression over 8 years in a community-based sample of
      elderly women with radiographic findings of hip osteoarthritis (RHOA) with or
      without hip pain. METHODS: Baseline and followup anteroposterior pelvic
      radiographs were obtained at a mean +/- SD 8.3 +/- 0.4 years of followup in women
      age > or =65 years at the baseline examination of the Study of Osteoporotic
      Fractures. We evaluated progression in 936 hips of 745 women with one or more
      baseline findings of RHOA: summary OA grade > or =2, minimum joint space (MJS) <
      or =1.5 mm, definite femoral or acetabular osteophytes, definite superolateral
      joint space narrowing (JSN), or moderate or worse superomedial JSN. We separately
      examined progression in hips with an MJS between 1.5 mm and 2.5 mm. Hip pain and
      lower extremity disability were assessed by questionnaire and examination.
      Measures of progression included an increase in summary grade of radiographic
      findings, increase in total osteophyte score, decrease in MJS of > or =0.5 mm,
      total hip replacement (THR), and increase in lower extremity disability score.
      Odds ratios (ORs) and 95% confidence intervals (95% CIs) for baseline
      radiographic predictors of progression were estimated using general estimating
      equations. RESULTS: During followup, 12.9% of women with baseline RHOA underwent
      THR, and 22.8% had substantial worsening of lower extremity disability, while
      64.6% of hips with RHOA showed radiographic progression or were replaced.
      Progression was greater by all measures in the 37% of hips and 47% of women with
      both RHOA and hip pain at baseline. Of hips with pain, 23.6% progressed to THR
      compared with 2.7% of hips without pain (OR 8.1 [95% CI 4.2, 15.4], P < 0.001),
      and MJS decreased > or =0.5 mm in 53.7% of hips with pain compared with 30.7% of
      hips without pain (OR 1.9 [95% CI 1.4, 2.6], P < 0.001). Women with hip pain were
      more likely to have worsened lower extremity disability (29.3% versus 17.6%; OR
      1.8 [95% CI 1.2, 2.8], P = 0.0053). Hips with an MJS >1.5 mm and < or =2.5 mm (n
      = 1,868) had primarily superomedial narrowing and comparatively low rates of
      progression that did not differ by hip pain. Femoral osteophytes, superolateral
      JSN, and subchondral bone changes were independent predictors of progression.
      CONCLUSION: Among women recruited from the community, radiographic and clinical
      progression was greater in those with symptomatic RHOA, but still substantially
      less frequent than previously reported for hip OA patients in clinical settings.
      Asymptomatic RHOA and hips with an isolated finding of mild JSN (MJS of 1.5 mm to
      2.5 mm) were unlikely to progress over 8 years.

PMID- 15146418
TI  - Distribution of radiographic osteoarthritis between the right and left hands,
      hips, and knees.
AB  - OBJECTIVE: To investigate whether radiographic osteoarthritis (OA) is asymmetric
      and greater on the right side than on the left side in the hands, hips, and
      knees. METHODS: Participants were 489 individuals with posteroanterior hand
      radiographs from a family study of nodal OA, 1,715 community-derived individuals
      who had undergone intravenous urography with views of both hips, and 1,729
      community-derived individuals with weight-bearing fully extended tibiofemoral
      (TF) joint and skyline patellofemoral (PF) joint radiographs. All radiographs
      were evaluated for global OA grade, osteophytes, and joint space narrowing (JSN).
      Minimum joint space width (JSW) was measured at the hip and knee. Odds ratios
      (ORs) for global OA on the right side versus the left side were calculated.
      Osteophytes and JSN were compared by Wilcoxon's signed rank test, and the JSW was
      compared by paired t-test. RESULTS: Global OA was more prevalent on the right
      side at the distal interphalangeal joints (OR 1.57; 95% confidence interval 1.22,
      2.02) and the TF joint (OR 1.24; 95% confidence interval 1.01, 1.52). Osteophyte
      scores for the fingers were greater on the right side, but JSN was symmetric. At
      the hip, there were no right-left differences in osteophytosis or JSN, but the
      JSW was smaller on the left. At the TF joint, the medial compartment was narrower
      and the lateral compartment wider on the right side, and osteophyte scores were
      greater on the right side. At the PF joint, there were no right-left differences
      in osteophytes, and for lone PF joint OA, there were no differences in JSN or the
      JSW. CONCLUSION: This discordance in symmetry suggests that the relative
      importance of biomechanical factors in the pathogenesis of OA is site-specific
      and may be discordant for cartilage and bone.

PMID- 15146419
TI  - Chopstick arthropathy: the Beijing Osteoarthritis Study.
AB  - OBJECTIVE: Several investigators have speculated that mechanical stress might
      play an important role in the development of hand osteoarthritis (OA).
      Chopsticks, used universally as eating utensils in China, increase joint loading
      in the first through third fingers. We conducted a population-based survey among
      elderly Chinese individuals living in Beijing, to explore whether chopsticks use
      is associated with prevalent hand OA. METHODS: We recruited a sample of persons
      ages 60 years and older, using door-to-door enumeration in randomly selected
      neighborhoods in Beijing. Subjects answered questions about the hand with which
      they use chopsticks, handedness, and pincer grip activities. Bilateral
      posteroanterior hand radiographs were obtained, and each joint was graded
      according to the Kellgren/Lawrence (K/L) scale. We defined a subject as having
      radiographic OA if at least 1 of his or her hand joints had radiographic OA (K/L
      score of > or =2). We defined a particular hand group (i.e., distal
      interphalangeal [DIP] joints, proximal interphalangeal [PIP] joints, or
      metacarpophalangeal [MCP] joints) as having OA if at least 1 joint of the group
      had radiographic OA. We calculated the prevalence of OA for each hand joint and,
      according to the status of chopsticks use, performed a matched analysis to
      examine the relationship between chopsticks use and the prevalence of hand OA. In
      the analysis, we excluded persons who reported a previous hand injury. Because
      most subjects used chopsticks with their dominant hand (a hand they would be
      expected to use more for all manual tasks), we also performed the analysis among
      subjects who reported that they had no hand preference when performing other
      activities and subjects who denied other pincer grip activities. RESULTS: A total
      of 1,008 men and 1,499 women were assessed. The prevalence ratio for OA of the
      thumb IP joint in the chopsticks hand was 1.2 (range 1.1-1.4) in men and 1.6
      (range 1.4-1.7) in women; the prevalence ratio for OA of the second and third PIP
      joints was 1.5 (range 1.1-2.2) in men and 1.4 (range 1.2-1.7) in women; and the
      prevalence ratio for OA of the second and third MCP joints was 1.4 (range 1.2
      1.6) in men and 1.4 (range 1.2-1.6) in women. The prevalence ratios in these
      joints were greater than the ratios in other MCP, PIP, or DIP joints from the
      same hand that were unlikely to be involved by chopsticks use, especially among
      women. Similar results were observed when the analyses were limited to
      ambidextrous subjects and subjects who did not engage in any other pincer grip
      activities. Thumb IP joint OA affected 26% of the entire population studied, and
      chopsticks use accounted for 19% of the risk of OA developing in this joint in
      men and 36% of the risk in women. CONCLUSION: This epidemiologic study
      investigated the relationship of chopsticks use to hand arthropathy. The results
      suggest that chopsticks use is associated with an increased prevalence of OA in
      the IP joint of the thumb, and in the second and third PIP and MCP joints.

PMID- 15146420
TI  - Exercise and dietary weight loss in overweight and obese older adults with knee
      osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial.
AB  - OBJECTIVE: The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was a
      randomized, single-blind clinical trial lasting 18 months that was designed to
      determine whether long-term exercise and dietary weight loss are more effective,
      either separately or in combination, than usual care in improving physical
      function, pain, and mobility in older overweight and obese adults with knee
      osteoarthritis (OA). METHODS: Three hundred sixteen community-dwelling overweight
      and obese adults ages 60 years and older, with a body mass index of > or =28
      kg/m(2), knee pain, radiographic evidence of knee OA, and self-reported physical
      disability, were randomized into healthy lifestyle (control), diet only, exercise
      only, and diet plus exercise groups. The primary outcome was self-reported
      physical function as measured with the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). Secondary outcomes included weight loss, 6-minute
      walk distance, stair-climb time, WOMAC pain and stiffness scores, and joint space
      width. RESULTS: Of the 316 randomized participants, 252 (80%) completed the
      study. Adherence was as follows: for healthy lifestyle, 73%; for diet only, 72%;
      for exercise only, 60%; and for diet plus exercise, 64%. In the diet plus
      exercise group, significant improvements in self-reported physical function (P <
      0.05), 6-minute walk distance (P < 0.05), stair-climb time (P < 0.05), and knee
      pain (P < 0.05) relative to the healthy lifestyle group were observed. In the
      exercise group, a significant improvement in the 6-minute walk distance (P <
      0.05) was observed. The diet-only group was not significantly different from the
      healthy lifestyle group for any of the functional or mobility measures. The
      weight-loss groups lost significantly (P < 0.05) more body weight (for diet,
      4.9%; for diet plus exercise, 5.7%) than did the healthy lifestyle group (1.2%).
      Finally, changes in joint space width were not different between the groups.
      CONCLUSION: The combination of modest weight loss plus moderate exercise provides
      better overall improvements in self-reported measures of function and pain and in
      performance measures of mobility in older overweight and obese adults with knee
      OA compared with either intervention alone.

PMID- 15146421
TI  - Proteomic surveillance of autoimmunity in osteoarthritis: identification of
      triosephosphate isomerase as an autoantigen in patients with osteoarthritis.
AB  - OBJECTIVE: Autoimmunity to proteins, such as type II collagen and cartilage
      intermediate layer protein, that are produced by chondrocytes has been reported
      in patients with osteoarthritis (OA) as well as in patients with rheumatoid
      arthritis (RA). However, it remains to be determined whether the overall
      specificities of the autoimmunity differ between OA and RA patients. This study
      sought to clarify the differences by applying proteomic surveillance for the
      detection of autoantigens comprehensively. METHODS: Serum samples were obtained
      from 20 patients with OA, 20 patients with RA, and 20 healthy volunteers. Human
      chondrocyte proteins were separated from the sera by 2-dimensional
      electrophoresis, and antigenic protein spots were detected by Western blotting.
      The antigenic proteins were then identified by mass fingerprinting. The
      antigenicity of the identified proteins was confirmed and the prevalence of the
      autoantibodies in the OA, RA, and other disease groups was determined with the
      use of recombinant proteins. In addition, autoepitopes were mapped on the
      antigens. RESULTS: Nineteen protein spots were recognized only by the OA sera,
      but not by the RA sera. One of these proteins was identified as triosephosphate
      isomerase (TPI). IgG-type anti-TPI autoantibodies were detected in 24.7% of the
      serum samples and 24.1% of the synovial fluid samples from the patients with OA,
      whereas <6% of the RA and systemic lupus erythematosus samples were positive for
      anti-TPI. In addition, multiple autoepitopes were identified on TPI. CONCLUSION:
      The overall profile of autoimmunity in OA differs from that in RA, which may
      reflect the OA-specific pathologic role of autoimmunity. The autoantibody to TPI,
      detected predominantly in the OA samples and produced by the antigen-driven
      mechanism, has the potential to be used as a diagnostic marker for OA.

PMID- 15146422
TI  - Identification of mesenchymal progenitor cells in normal and osteoarthritic human
      articular cartilage.
AB  - OBJECTIVE: To determine the presence of mesenchymal progenitor cells (MPCs) in
      human articular cartilage. METHODS: Primary cell cultures established from normal
      and osteoarthritic (OA) human knee articular cartilage were analyzed for the
      expression of CD105 and CD166, cell surface markers whose coexpression defines
      mesenchymal stem cells (MSCs) in bone marrow and perichondrium. The potential of
      cartilage cells to differentiate to adipogenic, osteogenic, and chondrogenic
      lineages was analyzed after immunomagnetic selection for CD105+/CD166+ cells and
      was compared with bone marrow-derived MSCs (BM-MSCs). RESULTS: Up to 95% of
      isolated cartilage cells were CD105+ and approximately 5% were CD166+. The mean
      +/- SEM percentage of CD105+/CD166+ cells in normal cartilage was 3.49 +/- 1.93%.
      Primary cell cultures from OA cartilage contained significantly increased numbers
      of CD105+/CD166+ cells. Confocal microscopy confirmed the coexpression of both
      markers in the majority of BM-MSCs and a subpopulation of cartilage cells.
      Differentiation to adipocytes occurred in cartilage-derived cell cultures, as
      indicated by characteristic cell morphology and oil red O staining of lipid
      vacuoles. Osteogenesis was observed in isolated CD105+/CD166+ cells as well as in
      primary chondrocytes cultured in the presence of osteogenic supplements. Purified
      cartilage-derived CD105+/CD166+ cells did not express markers of differentiated
      chondrocytes. However, the cells were capable of chondrocytic differentiation and
      formed cartilage tissue in micromass pellet cultures. CONCLUSION: These findings
      indicate that multipotential MPCs are present in adult human articular cartilage
      and that their frequency is increased in OA cartilage. This observation has
      implications for understanding the intrinsic repair capacity of articular
      cartilage and raises the possibility that these progenitor cells might be
      involved in the pathogenesis of arthritis.

PMID- 15146423
TI  - Antibodies to guanosine triphosphate misidentified as anti-double-stranded DNA
      antibodies in a patient with antinuclear antibody-negative lupus, due to buckling
      of insolubilized assay DNA.
AB  - OBJECTIVE: To investigate why the serum of a pediatric patient with systemic
      lupus erythematosus was persistently (>30 months) and strongly positive for
      antibodies to double-stranded DNA (dsDNA) as revealed by enzyme-linked
      immunosorbent assay (ELISA), but yielded negative results on the antinuclear
      antibody test (HEp-2 immunofluorescence [IF]). METHODS: The patient's antibodies
      were isolated on dsDNA and single-stranded DNA (ssDNA) supports, which were then
      examined by dsDNA ELISA and HEp-2 IF. Tests included the use of various
      inhibitors to determine the fine specificity of the antibodies. Other tests
      performed included immunoblotting, immunoprecipitation, Crithidia luciliae IF,
      and neutrophil IF. RESULTS: The antibodies isolated from the dsDNA and ssDNA
      supports were similar, in that they were of the IgG type, bound well in the dsDNA
      ELISA, and recognized a normally hidden nucleolar RNA antigen in HEp-2 cells.
      With both the dsDNA ELISA and nucleolar antigens, inhibition studies revealed
      that the epitope recognized was guanosine 5'-triphosphate (GTP). Binding of the
      antibodies was better to GTP than to guanosine 5'-monophosphate or cytidylyl (3'
      5') guanosine, and, in turn, was better than to guanosine, while N7-methylated
      GTP was unreactive. The antibodies did not bind to dsDNA present in solution or
      in HEp-2 or Crithidia cells, but bound transfer RNA well and recognized a
      cytoplasmic RNA antigen in neutrophils. CONCLUSION: A new problem in dsDNA ELISA
      is revealed in the occurrence of a hitherto-unknown and unusual buckling of the
      insolubilized DNA molecule, which, absent in dsDNA found in solution or in whole
      cells, presumably creates gaps of single-strandedness in the molecule. A new
      antibody specific for GTP is described in this patient, which may be clinically
      important.

PMID- 15146424
TI  - Prevention of renal damage in murine lupus nephritis by CTLA-4Ig and
      cyclophosphamide.
AB  - OBJECTIVE: To compare the effects of combined administration of cyclophosphamide
      (CYC) and CTLA-4Ig with the effects of these agents alone on the immunopathology
      and progression of renal damage in (NZB x NZW)F(1) (B/W) lupus-prone mice, and to
      explore the clinical implications of this combination by evaluating the ability
      of CTLA-4Ig to sustain the benefit of CYC in patients with lupus nephritis.
      METHODS: We carried out a detailed, prospective pathologic and
      immunohistochemical analysis of the effects of CYC and CTLA-4Ig, alone and in
      combination, in kidney tissue from B/W mice. The acute effects of these agents on
      immune cells in the kidney were evaluated by fluorescence-activated cell sorting.
      We also compared the effect of brief CYC plus sustained CTLA-4Ig administration
      with the effect of sustained administration of both agents on the progression of
      renal disease in B/W mice. RESULTS: As a single agent, CTLA-4Ig was generally as
      effective, and in some cases more effective, than CYC in slowing progression of
      renal disease. Combined therapy with these two agents very effectively arrested
      the progression of renal damage and, in some respects, reversed renal pathology.
      Induction therapy with both CTLA-4Ig and CYC precluded the need for continuous
      administration of CYC. CONCLUSION: Our results indicate that the combination of
      CTLA-4Ig and CYC very effectively arrests the progression of murine lupus
      nephritis. These findings have direct implications for the treatment of lupus
      nephritis.

PMID- 15146425
TI  - Requirement of dying cells and environmental adjuvants for the induction of
      autoimmunity.
AB  - OBJECTIVE: Cells commonly die without eliciting autoimmunity. However, dying
      cells are a potential initiating stimulus for systemic lupus erythematosus (SLE).
      Our goal was to verify whether immune adjuvants influence the autoimmunity
      induction that ensues following in vivo injection of dying cells. METHODS: Mice
      were immunized with apoptotic thymocytes in the presence of artificial moieties,
      such as Freund's incomplete adjuvant (IFA), or natural adjuvants, such as
      dendritic cells (DCs). Renal involvement and the development of autoantibodies
      were monitored. RESULTS: Apoptotic cells failed to induce clinical disease or to
      sustain production of autoantibodies in (NZB x NZW)F(1) mice. In contrast,
      autoimmunity developed in the presence of IFA or DCs. The characteristics of the
      adjuvant influenced the array of autoantibodies, the kinetics of their
      development, and the severity of the disease. DCs were required for induction of
      anti-beta(2)-glycoprotein I IgG. Adjuvants alone did not elicit disease.
      CONCLUSION: A "two-hit" signal composed of autoantigens and adjuvants initiates
      systemic autoimmunity. Moreover, environmental signals at the site of clearance
      of dead cells shape the features and the severity of the autoimmune disease.
      Strategies aimed at preventing the accumulation of dying cells and at modulating
      endogenous adjuvants may be beneficial for the treatment of SLE.

PMID- 15146426
TI  - Association of killer cell immunoglobulin-like receptors with scleroderma.
AB  - OBJECTIVE: Scleroderma is an autoimmune disorder of unknown etiology. A genetic
      contribution has been demonstrated, and genes influencing activation of the
      immune system have been potentially identified as candidate genes in this
      process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that
      are involved in the activation of T cells and natural killer cells is highly
      variable. Recently, an association of KIR2DS2 with vasculitis in patients with
      rheumatoid arthritis has been reported. Because scleroderma is characterized by
      an involvement of the vascular system, we sought to determine whether KIR2DS2 is
      associated with scleroderma. METHODS: We typed 9 KIR genes in 102 patients with
      scleroderma and in 100 blood donors, using polymerase chain reaction on genomic
      DNA. RESULTS: Twelve patients with scleroderma, compared with only 2 blood
      donors, had KIR phenotypes characterized by the presence of the activating
      KIR2DS2 and the absence of the corresponding inactivating KIR2DL2 (P = 0.005).
      CONCLUSION: The genetic combination of KIR2DS2+ and KIR2DL2- is associated with
      scleroderma.

PMID- 15146427
TI  - An increased transforming growth factor beta receptor type I:type II ratio
      contributes to elevated collagen protein synthesis that is resistant to
      inhibition via a kinase-deficient transforming growth factor beta receptor type
      II in scleroderma.
AB  - OBJECTIVE: Aberrant transforming growth factor beta (TGFbeta) signaling has been
      implicated in the pathogenesis of scleroderma (systemic sclerosis [SSc]), but the
      contribution of specific components in this pathway to SSc fibroblast phenotype
      remains unclear. This study was undertaken to delineate the role of TGFbeta
      receptor type I (TGFbetaRI) and TGFbetaRII in collagen overexpression by SSc
      fibroblasts. METHODS: Primary dermal fibroblasts from SSc patients and healthy
      adults were studied (n = 10 matched pairs). Adenoviral vectors were generated for
      TGFbetaRI (AdTGFbetaRI), TGFbetaRII (AdTGFbetaRII), and kinase-deficient
      TGFbetaRII (AdDeltakRII). TGFbetaRI basal protein levels were analyzed by (35)S
      methionine labeling/immunoprecipitation and immunohistochemistry. Type I collagen
      and TGFbetaRII basal protein levels were analyzed by Western blot and newly
      secreted collagen by (3)H-proline incorporation assay. RESULTS: Analysis of
      endogenous TGFbetaRI and TGFbetaRII protein levels revealed that SSc TGFbetaRI
      levels were increased 1.7-fold (P = 0.008; n = 7) compared with levels in healthy
      controls, while TGFbetaRII levels were decreased by 30% (P = 0.03; n = 7). This
      increased TGFbetaRI:TGFbetaRII ratio correlated with SSc collagen overexpression.
      To determine the consequences of altered TGFbetaRI:TGFbetaRII ratio on collagen
      expression, healthy fibroblasts were transduced with AdTGFbetaRI or AdTGFbetaRII.
      Forced expression of TGFbetaRI in the range corresponding to elevated SSc
      TGFbetaRI levels increased basal collagen expression in a dose-dependent manner,
      while similar TGFbetaRII overexpression had no effect, although transduction of
      fibroblasts at higher multiplicities of infection led to a marked reduction of
      basal collagen levels. Blockade of TGFbeta signaling via AdDeltakRII resulted in
      approximately 50% inhibition of basal collagen levels in healthy fibroblasts and
      in 5 of 9 SSc cell lines. A subset of SSc fibroblasts (4 of 9 cell lines) was
      resistant to this treatment. SSc fibroblasts with the highest levels of TGFbetaRI
      were the least responsive to collagen inhibition via DeltakRII. CONCLUSION: This
      study indicates that an increased TGFbetaRI:TGFbetaRII ratio may underlie
      aberrant TGFbeta signaling in SSc and contribute to elevated basal collagen
      production, which is insensitive to TGFbeta signaling blockade via DeltakRII.

PMID- 15146428
TI  - Increased tyrosine phosphorylation mediates the cooling-induced contraction and
      increased vascular reactivity of Raynaud's disease.
AB  - OBJECTIVE: Increased levels of protein tyrosine kinase (PTK) are mechanistically
      associated with increased contractile responsiveness to cooling. This study tests
      the hypothesis that increased PTK activity mediates the increased vascular
      reactivity to agonists and cooling associated with primary Raynaud's disease
      (RD). METHODS: The response of dermal arterioles isolated from control (n = 29)
      and RD (n = 29) subjects to contractile and dilatory agents at 37 degrees C and
      31 degrees C was characterized using the microvessel perfusion technique.
      Fluorescence immunohistochemistry was used to measure tyrosine phosphorylation.
      RESULTS: At 37 degrees C, arteries from RD patients exhibited similar sensitivity
      to the specific alpha(2)-adrenergic agonist UK 14,304, to serotonin, and to
      angiotensin II. At 31 degrees C, however, the response to all 3 agonists was
      greater in the arterioles from the RD patients than in those from the control
      subjects. Agonist-induced contraction at both temperatures was reversed by
      cumulative addition of the PTK inhibitors genistein (1-30 microM) and tyrphostin
      47 (0.1-10 microM). All arterioles from control subjects relaxed slightly in
      response to cooling, whereas more than half of those from RD patients contracted.
      This cooling-induced contraction was reversed by the cumulative addition of
      genistein. The 3 agonists elicited large increases in tyrosine phosphorylation
      only in arterial segments from RD patients at 31 degrees C. Cooling from 37
      degrees C to 31 degrees C elicited a large increase in tyrosine phosphorylation
      in arterioles from RD patients, but not those from control subjects. All
      increases in tyrosine phosphorylation could be prevented by genistein.
      CONCLUSION: Increased tyrosine phosphorylation mediates cooling-induced
      contraction and the increased vascular reactivity of skin arterioles from
      individuals with RD.

PMID- 15146430
TI  - Validation and clinical significance of the Childhood Myositis Assessment Scale
      for assessment of muscle function in the juvenile idiopathic inflammatory
      myopathies.
AB  - OBJECTIVE: To examine the measurement characteristics of the Childhood Myositis
      Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory
      myopathy (juvenile IIM), and to obtain preliminary data on the clinical
      significance of CMAS scores. METHODS: One hundred eight children with juvenile
      IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of
      physical function, strength, and disease activity. Interrater reliability,
      construct validity, and responsiveness of the CMAS were examined. The minimum
      clinically important difference (MID) and CMAS scores corresponding to various
      degrees of physical disability were estimated. RESULTS: The intraclass
      correlation coefficient for 26 patients assessed by 2 examiners was 0.89,
      indicating very good interrater reliability. The CMAS score correlated highly
      with the Childhood Health Assessment Questionnaire (C-HAQ) score and with
      findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and
      moderately with physician-assessed global disease activity and skin activity,
      parent-assessed global disease severity, and muscle magnetic resonance imaging
      (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The
      standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in
      patients with at least 0.8 cm improvement on a 10-cm visual analog scale for
      physician-assessed global disease activity, indicating strong responsiveness. In
      bivariate regression models predicting physician-assessed global disease
      activity, MMT remained significant in models containing the CMAS (P = 0.03) while
      the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points
      on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate,
      and moderate physical disability, respectively, were 48, 45, 39, and 30.
      CONCLUSION: The CMAS exhibits good reliability, construct validity, and
      responsiveness, and is therefore a valid instrument for the assessment of
      physical function, muscle strength, and endurance in children with juvenile IIM.
      Preliminary data on MID and corresponding levels of disability should aid in the
      clinical interpretation of CMAS scores when assessing patients with juvenile IIM.

PMID- 15146429
TI  - Down-regulation of the aberrant expression of the inflammation mediator high
      mobility group box chromosomal protein 1 in muscle tissue of patients with
      polymyositis and dermatomyositis treated with corticosteroids.
AB  - OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB-1) is an
      endogenous nuclear protein that can be translocated to the cytoplasm and then
      released extracellularly. It can induce tumor necrosis factor and interleukin-1
      production in myeloid cells. Increased expression of these 2 cytokines has been
      observed in muscle tissue of patients with polymyositis (PM) and dermatomyositis
      (DM). The present study was therefore undertaken to investigate how HMGB-1 is
      expressed in muscle tissue of patients with myositis and, if so, whether such
      expression is modulated by prednisolone therapy. METHODS: Muscle biopsy specimens
      from 5 patients with PM and 4 patients with DM, obtained before and 3-6 months
      after initiation of prednisolone therapy, were assessed by conventional
      microscopic evaluation and computerized image analysis, and HMGB-1 expression was
      investigated by immunohistochemical staining. Muscle biopsy specimens from 7
      healthy controls were also studied. RESULTS: Cytoplasmic HMGB-1 expression was
      detected in infiltrating rounded mononuclear cells, vascular endothelial cells,
      and muscle fibers of PM and DM patients. Extracellular staining surrounding the
      inflammatory cells was also observed. After treatment with high-dose
      prednisolone, cytoplasmic and extracellular HMGB-1 expression was significantly
      reduced, coinciding mainly with a decreased number of infiltrating inflammatory
      cells. Cytoplasmic HMGB-1 expression was still evident in endothelial cells and
      muscle fibers. No HMGB-1 expression was observed in muscle tissue from healthy
      controls. CONCLUSION: The cytoplasmic and extracellular distribution of HMGB-1 in
      muscle tissue may indicate an important role of this proinflammatory molecule in
      the pathogenesis of PM and DM. Furthermore, our findings indicate that
      systemically administered high-dose corticosteroids selectively down-regulate
      aberrant expression of HMGB-1 in mononuclear inflammatory cells in vivo.

PMID- 15146431
TI  - A functional promoter haplotype of macrophage migration inhibitory factor is
      linked and associated with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To establish linkage and replicate the association of macrophage
      migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA).
      METHODS: Three hundred twenty-one Caucasian simplex families from the UK were
      genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a
      fluorescently labeled primer method, and capillary gel electrophoresis. The
      functional significance of the promoter polymorphisms was studied using
      luciferase-based reporter gene assays in human T lymphoblast and epithelial cell
      lines. RESULTS: MIF was linked and associated with JIA (P = 0.0016).
      Specifically, a 2-point promoter haplotype, CATT(7)-MIF-173*C, was found to be
      transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients.
      Conditional extended transmission disequilibrium test and pairwise extended
      transmission disequilibrium test predicted functional interaction between the 2
      polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was
      found to be specific to the cell type. CONCLUSION: Replication of an association
      and linkage of MIF with JIA has been established. Functional interaction between
      the polymorphic positions on the linked haplotype has also been shown. The
      molecular mechanism of this interaction is currently being investigated.

PMID- 15146433
TI  - Defective costimulatory function is a striking feature of antigen-presenting
      cells in an HLA-B27-transgenic rat model of spondylarthropathy.
AB  - OBJECTIVE: A disease resembling the human spondylarthropathies develops in HLA
      B27-transgenic rats. This disease in rats is mediated by CD4+ T cells, but
      antigen-presenting cells (APCs) may also play a role. Dendritic cells (DCs) have
      been reported to be defective in allogeneic mixed lymphocyte culture in this
      model. Here, we further investigated the functional defect of APCs. METHODS: DCs
      and B cells from nontransgenic, HLA-B27 (33-3)-transgenic, and HLA-B7 (120-4)
      transgenic rats were used to stimulate T cells. Surface expression of HLA-B
      transgene and rat molecules on APCs and the formation of conjugates between DCs
      and T cells were monitored by flow cytometry. RESULTS: We observed a strikingly
      defective stimulation of allogeneic and syngeneic T lymphocytes by APCs from HLA
      B27 but not HLA-B7 rats, even if stimulation was driven in the presence of anti-T
      cell receptor (TCR) antibody. We found no evidence that HLA-B27 DCs were
      immature, lacked production of some diffusible factor, or produced an inhibitory
      factor for T cells. When comparing the levels of expression of class II major
      histocompatibility complex, CD2, intercellular adhesion molecule 1, lymphocyte
      function-associated antigen 1, B7, and CD40 molecules at the surface of DCs from
      33-3, 120-4, and nontransgenic rats, we found little difference. However, HLA-B27
      transgenic DCs formed fewer conjugates with T cells than did nontransgenic DCs.
      Furthermore, the proportion of conjugates formed between DCs and T cells, as well
      as the difference between nontransgenic and HLA-B27-transgenic DCs, were in large
      part reduced by blocking CD86 on DCs. CONCLUSION: We confirmed defective
      stimulation of T cells by APCs in HLA-B27 rats, the mechanism of which appears to
      implicate APC/T cell contact, independent of TCR engagement. In addition,
      decreased use of the CD86 costimulatory molecule by B27 DCs was observed.
      Impaired costimulatory function could result in a loss of tolerance toward
      microbial flora in this model.

PMID- 15146432
TI  - Association of CD163+ macrophages and local production of soluble CD163 with
      decreased lymphocyte activation in spondylarthropathy synovitis.
AB  - OBJECTIVE: Since CD163+ macrophages are selectively increased in
      spondylarthropathy (SpA) synovitis, we investigated the role of CD163+
      macrophages in synovial inflammation. METHODS: Synovial biopsy samples from 26
      SpA and 23 rheumatoid arthritis (RA) patients were analyzed for macrophage and
      lymphocyte subsets. Synovial fluid (SF) samples were analyzed by Western blotting
      and enzyme-linked immunosorbent assay for soluble CD163 (sCD163) and by flow
      cytometry for lymphocyte activation. We also analyzed sCD163 in sera from 100 SpA
      patients, 23 RA patients, 20 healthy controls, and 20 SpA patients treated with
      infliximab. Polymorphism of haptoglobin (Hp), the CD163 ligand, was determined in
      130 SpA and 23 RA patients. RESULTS: CD163+ macrophages, but not CD68+
      macrophages, were significantly increased in SpA versus RA synovium and in HLA
      B27+ versus HLA-B27- SpA. Despite similar lymphocyte numbers, activated
      lymphocytes (CD69+) were significantly decreased in SpA versus RA patients, with
      an inverse correlation between CD163 and CD69 levels. Local production of sCD163
      was evidenced by a 5-7-fold higher level of sCD163 in SF than in serum and by the
      correlation with synovial lining CD163+ macrophages in SpA. SF sCD163 levels
      correlated directly with global inflammation but correlated inversely with CD69+
      SF T lymphocytes in the synovium. In contrast, serum sCD163 levels were only
      moderately increased, did not correlate with SF sCD163 levels or parameters of
      inflammation, and were unaffected by infliximab therapy. The distribution of Hp
      polymorphism was not altered in SpA and was not related to CD163 expression.
      CONCLUSION: Increased numbers of CD163+ macrophages in SpA synovium and local
      production of sCD163 are associated with global inflammation as well as
      impairment of T cell activation, suggesting a dual role for CD163+ macrophages in
      SpA synovitis.

PMID- 15146434
TI  - Antiangiogenic effects of anti-tumor necrosis factor alpha therapy with
      infliximab in psoriatic arthritis.
AB  - OBJECTIVE: Neovascularization, with an increased number of synovial vessels with
      a characteristic morphology, seems to contribute to the progression of psoriatic
      arthritis (PsA). Accordingly, angiogenesis may be an important therapeutic target
      in PsA. The aim of this study was to analyze the effects of infliximab on
      angiogenesis in the synovial membrane of patients with PsA who responded to this
      therapy. METHODS: The study group comprised 9 patients with PsA who were selected
      for the presence of active polyarthritis (including knee synovitis) despite
      methotrexate therapy. Clinical and biologic evaluations were performed at each
      visit. Arthroscopy and synovial biopsies were performed at week 0, before
      infliximab therapy was initiated, and at week 8, after administration of 3
      intravenous infusions of infliximab (5 mg/kg). We used immunohistochemistry to
      identify changes in infiltrating cells and in the angiogenesis modulators
      alphavbeta3 integrin, vascular endothelial growth factor (VEGF), angiopoietin 2
      (Ang-2), flt-1 (VEGF receptor 1 [VEGFR-1]), kinase insert domain receptor
      [KDR]/flk-1 (VEGFR-2), and stromal cell-derived factor 1 (SDF-1).
      Neovascularization was assessed by automated histomorphometry of CD31+ vessels
      and by measuring alphavbeta3 expression. RESULTS: Rapid and significant clinical
      and biological improvement were observed after treatment in all patients. In the
      synovium, infliximab therapy induced a significant reduction in macrophages, the
      CD31+ vascular area, alphavbeta3+ neovessels/Ulex europaeus agglutinin+ vessels,
      VEGF and its receptor KDR/flk-1 (VEGFR-2), and SDF-1+ vessels. Expression of flt
      1 (VEGFR-1), and SDF-1 in lining cells showed a nonsignificant reduction, whereas
      expression of Ang-2 increased. In 3 patients, reverse transcription-polymerase
      chain reaction confirmed the changes in some of these markers at the messenger
      RNA level. CONCLUSION: These results show consistent changes in several factors
      involved in angiogenesis regulation, in parallel with the clinical response to
      infliximab in patients with PsA. The pattern of reduced VEGF with increased Ang-2
      suggests vascular regression as a potential mechanism underlying the
      antiangiogenic effect of infliximab.

PMID- 15146435
TI  - Basic calcium phosphate crystal-induced prostaglandin E2 production in human
      fibroblasts: role of cyclooxygenase 1, cyclooxygenase 2, and interleukin-1beta.
AB  - OBJECTIVE: To elucidate the mechanism of basic calcium phosphate (BCP) crystal
      induced prostaglandin E(2) (PGE(2)) production in human foreskin fibroblasts
      (HFFs), to identify the signaling pathway involved in the induction of
      cyclooxygenase 2 (COX-2) messenger RNA (mRNA) by BCP crystals, to examine the
      effect of BCP crystals on interleukin-1beta (IL-1beta) mRNA expression, and to
      investigate the potential of phosphocitrate to abrogate the BCP crystal-induced
      effects. METHODS: PGE(2) levels were quantified using a commercial enzyme
      immunoassay kit. COX-2 and COX-1 transcript levels were quantified using real
      time reverse transcriptase-polymerase chain reaction (RT-PCR). Induction of IL
      1beta and COX-2 mRNA was examined by end-point RT-PCR. COX-2 protein expression
      was assessed by Western blotting. RESULTS: PGE(2) production measured 4 and 30
      hours after BCP crystal treatment was higher in BCP crystal-treated (mean +/- SEM
      1,891 +/- 273 pg/microg and 1,792 +/- 233 pg/microg, respectively) than in
      untreated (88 +/- 5 pg/microg and 205 +/- 93 pg/microg, respectively) HFFs. The
      PGE(2) produced after 4 hours was sensitive to inhibition with NS398, a selective
      COX-2 inhibitor, implying that it was COX-2 mediated, whereas the PGE(2) produced
      at 30 hours could not be completely inhibited by NS398. Real-time RT-PCR
      demonstrated a 23-fold increase in COX-2 mRNA that was maximal at 4 hours,
      whereas analysis of mRNA for COX-1 showed up-regulation of transcript peaking at
      24 hours poststimulation (1.75-fold increase). The protein kinase C and
      phosphatidylinositol 3-kinase signal-transduction inhibitors bisindolylmaleimide
      I and LY294002, respectively, blocked BCP crystal-induced COX-2 mRNA in HFFs. In
      addition, BCP crystals were found to up-regulate the proinflammatory cytokine IL
      1beta (maximal at 8 hours). The induction of both COX-2 and IL-1beta by BCP
      crystals was attenuated when the cells were treated with phosphocitrate.
      CONCLUSION: These findings indicate that BCP crystals may be an important
      amplifier of PGE(2) production through induction of the COX enzymes and the
      proinflammatory cytokine IL-1beta.

PMID- 15146436
TI  - Familial Paget's disease in The Netherlands: occurrence, identification of new
      mutations in the sequestosome 1 gene, and their clinical associations.
AB  - OBJECTIVE: To estimate the occurrence of familial Paget's disease of bone in The
      Netherlands, to examine the prevalence of mutations of the sequestosome 1 gene
      (SQSTM1) in identified families, and to assess potential genotype-phenotype
      associations. METHODS: We performed a case-control study of patients with Paget's
      disease and a mutation analysis of the SQSTM1 gene of index patients with
      familial disease and of the relatives of those with a mutation. Serum alkaline
      phosphatase (AP) activity was assessed, and bone scintigraphy was performed.
      RESULTS: Five percent of patients had at least 1 first-degree relative with the
      disease, compared with 0.5% of the controls (relative risk 10; 95% confidence
      interval 1.3-75.6). In 38.9% of patients with familial disease, heterozygous
      mutations in the SQSTM1 gene were identified. These were the previously described
      P392L mutation, which was present in 22.2% of patients, and 3 new mutations,
      S399P, G425R, M404T, 9 of which were present in 3 different families. All
      mutations were located in the ubiquitin-associated domain of the gene. There was
      a relationship between serum AP activity, as a marker of the disease, and the
      presence or absence of the G425R and P392L mutations, the subject's age, and the
      presence of Paget's disease. CONCLUSION: Our data provide further evidence of a
      causal role of SQSTM1 gene mutations in the pathogenesis of Paget's disease and
      allow the design of a strategy based on measurements of serum AP activity and age
      for investigating asymptomatic relatives of patients with familial Paget's
      disease of bone.

PMID- 15146437
TI  - Mechanical injury and psychosocial factors in the work place predict the onset of
      widespread body pain: a two-year prospective study among cohorts of newly
      employed workers.
AB  - OBJECTIVE: Mechanical injury has been postulated as a risk factor for widespread
      pain, although to date, the evidence is weak. The aim of this study was to
      determine whether repeated exposure to mechanical trauma in the work place
      predicts the onset of widespread pain and to determine the relative contribution
      of mechanical trauma compared with psychosocial factors. METHODS: In this
      prospective cohort study of 1,081 newly employed subjects in 12 diverse
      occupational settings, we collected detailed information on mechanical exposure,
      posture, physical environment, and psychosocial risk factors in the work place.
      Study questionnaires were completed at baseline and at 12 and 24 months.
      Individuals free of widespread pain at baseline and 12 months were eligible for
      followup. Generalized estimating equations were used to determine which factors
      predicted the new onset of widespread pain. RESULTS: Of the 1,081 baseline
      respondents, 896 were free of widespread pain and were eligible for further
      study. Of these 896 subjects, 708 and 520 responded at 12 months and 24 months,
      respectively. The rates of new-onset widespread pain were 15% at 12 months and
      12% at 24 months. Several work place mechanical and posture exposures predicted
      the new onset of widespread pain: lifting >15 lbs with 1 hand, lifting >24 lbs
      with 2 hands, pulling >56 lbs, prolonged squatting, and prolonged working with
      hands at or above shoulder level. Of the psychosocial exposures, those who
      reported low job satisfaction, low social support, and monotonous work had an
      increased risk of new-onset widespread pain. In multivariate analysis, monotonous
      work and low social support were found to be the strongest independent predictors
      of symptom onset. CONCLUSION: Our findings demonstrate that the prevalence of new
      onset widespread pain was high, but among this young, newly employed work force,
      both physical and psychosocial factors played an important role.

PMID- 15146438
TI  - Achievement of a synergistic adjuvant effect on arthritis induction by activation
      of innate immunity and forcing the immune response toward the Th1 phenotype.
AB  - OBJECTIVE: To apply and analyze the mechanisms of action of
      dimethyldioctadecylammonium bromide (DDA), a powerful adjuvant that does not have
      the side effects of the conventionally used Freund's adjuvants, in proteoglycan
      induced arthritis (PGIA) and collagen-induced arthritis (CIA). METHODS: PGIA and
      CIA were generated using standard immunization protocols with cartilage
      proteoglycan aggrecan (PG) or human type II collagen (CII) emulsified with
      Freund's complete adjuvant (CFA), and compared with PGIA and CIA generated using
      immunization protocols in which the same antigens were used in combination with
      the adjuvant DDA. Immune responses to immunizing and self PGs and CII, and the
      incidence, severity, and onset of arthritis were monitored throughout the
      experiments. In addition, a new, inexpensive, and powerful method of inducing
      arthritis using crude cartilage extracts is described. RESULTS: A significantly
      reduced onset period and a more severe arthritis were achieved in BALB/c mice
      immunized with cartilage PGs in DDA. PGs from bovine, ovine, and porcine
      cartilage, which otherwise have no effect or have only a subarthritogenic effect,
      and crude extracts of human osteoarthritic cartilage induced a 100% incidence
      with a very high arthritis score in BALB/c mice. The overall immune responses to
      either CII or PG were similar in antigen/CFA-immunized and antigen/DDA-immunized
      animals, but the Th1/Th2 balance shifted significantly toward a Th1 bias in DDA
      injected animals with either PGIA or CIA. CONCLUSION: DDA, which was first used
      in autoimmune models, is a potent nonirritant adjuvant, which eliminates all
      undesired side effects of the Freund's adjuvants. DDA exerts a strong stimulatory
      effect via the activation of nonspecific (innate) immunity and forces the immune
      regulation toward Th1 dominance. These lines of evidence also suggest the
      possibility that seemingly innocuous compounds may exert an adjuvant effect in
      humans and may create the pathophysiologic basis of autoimmunity in susceptible
      individuals via the activation/stimulation of innate immunity.

PMID- 15146439
TI  - Antiinflammatory and analgesic effects of somatostatin released from capsaicin
      sensitive sensory nerve terminals in a Freund's adjuvant-induced chronic
      arthritis model in the rat.
AB  - OBJECTIVE: We previously demonstrated that somatostatin (SOM) released from the
      activated peripheral terminals of capsaicin-sensitive primary sensory neurons
      inhibits acute inflammation and nociception. This study was undertaken to examine
      this systemic "sensocrine" function of neuronally derived somatostatin in chronic
      inflammation in the Freund's complete adjuvant (CFA)-induced arthritis model.
      METHODS: Arthritis of the tibiotarsal joint of Lewis rats was evoked by
      subcutaneous injection of CFA into the left hind paw and the tail root. For 3
      weeks, the volume of the paws was measured by plethysmometry, and the
      mechanonociceptive thresholds were measured by esthesiometry. Plasma
      concentrations of SOM were determined by radioimmunoassay, and histologic studies
      of the joints were performed. To impair the function of capsaicin-sensitive
      afferents, the capsaicin receptor (VR1/TRPV1) agonist resiniferatoxin (RTX) was
      injected subcutaneously (30, 70, and 100 microg/kg on 3 subsequent days) 7 days
      before CFA administration. The SOM receptor antagonist cyclosomatostatin (c-SOM;
      20 microg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2
      x 50-400 microg/kg) was administered intraperitoneally every day. RESULTS: RTX
      pretreatment or c-SOM injection significantly increased edema and mechanical
      hyperalgesia of both CFA-treated and contralateral paws. The histologic score
      based on synovial thickening, cell infiltration, cartilage destruction, and bone
      erosion was also significantly higher both in the RTX- and the c-SOM-injected
      groups. These parameters were dose-dependently decreased by TT-232. Plasma SOM
      like immunoreactivity increased 4-fold on the twenty-first day, and was inhibited
      by RTX pretreatment, as well as by daily administration of TT-232. CONCLUSION:
      Our data suggest that SOM released into the circulation from capsaicin-sensitive
      afferents in response to prolonged activation exerts systemic antiinflammatory
      and analgesic effects. TT-232 can open new perspectives in the treatment of
      chronic arthritis.

PMID- 15146440
TI  - Suppressive oligonucleotides protect against collagen-induced arthritis in mice.
AB  - OBJECTIVE: To examine whether systemic administration of oligonucleotides (ODNs),
      known to inhibit the production of proinflammatory cytokines, alters host
      susceptibility to collagen-induced arthritis (CIA), a murine model of rheumatoid
      arthritis (RA). METHODS: CIA was induced by injecting DBA/1 mice with type II
      collagen (CII) in Freund's complete adjuvant, followed 3 weeks later by CII in
      Freund's incomplete adjuvant. The effect of suppressive ODNs on the incidence and
      severity of disease was monitored, as were immune correlates of CIA. RESULTS:
      Suppressive ODNs administered during the inductive phase of CIA significantly
      reduced the incidence and severity of arthritis. Treatment with suppressive ODNs
      significantly decreased serum titers of pathogenic IgG anti-CII autoantibodies
      and interferon-gamma production by collagen-reactive T cells. CONCLUSION:
      Suppressive ODNs may be of therapeutic value in the treatment of RA, and
      potentially other autoimmune diseases.

PMID- 15146441
TI  - Skin reaction to adalimumab.
AB  - The tumor necrosis factor alpha (TNFalpha) inhibitors etanercept and infliximab
      have shown good clinical results in the treatment of rheumatoid arthritis and
      other autoimmune disorders. With these novel fusion proteins, immune-mediated
      side effects, among them various cutaneous reactions, have been encountered. We
      report herein the case of an erythema multiforme-like skin reaction to treatment
      with the monoclonal anti-TNFalpha antibody adalimumab in a patient with
      rheumatoid arthritis. The reaction occurred after the sixth injection and
      affected the palms and soles as well as the injection site. Discontinuation of
      the adalimumab therapy resulted in rapid improvement of the condition. Although
      this patient was receiving concomitant immunomodulatory therapy with methotrexate
      and leflunomide, these medications were not discontinued when the reaction
      developed, and no other potential pathogenetic mechanisms were identified. We
      believe the reaction is most likely attributable to adalimumab.

PMID- 15146444
TI  - Signs of systemic disease are strong determinants of mortality in rheumatoid
      arthritis: comment on the article by Navarro-Cano et al.

PMID- 15146442
TI  - Soluble CD154 plasma levels in patients with systemic lupus erythematosus:
      modulation by antiphospholipid antibodies.

PMID- 15146445
TI  - Evidence for interaction between disease severity and comorbidity in rheumatoid
      arthritis? comment on the article by Navarro-Cano et al.

PMID- 15146447
TI  - Prospective comparison of sodium hyaluronate and hylan G-F 20 in a clinical
      practice: comment on the concise communication by Martens.

PMID- 15146449
TI  - Role of anti-glial fibrillary acidic protein antibodies in the pathogenesis of
      neuropsychiatric systemic lupus erythematosus should be clarified: comment on the
      article by Trysberg et al.

PMID- 15146451
TI  - Use of novel elution regimens of autoantibodies in lupus kidneys: comment on the
      article by Xie et al.

PMID- 15146452
TI  - Clinical images: Periarticular inflammation in rapidly developing Jaccoud's
      arthropathy.

PMID- 15146455
TI  - The androgen receptor gene mutations database (ARDB): 2004 update.
AB  - The current version of the androgen receptor (AR) gene mutations database is
      described. The total number of reported mutations has risen from 374 to 605, and
      the number of AR-interacting proteins described has increased from 23 to 70, both
      over the past 3 years. A 3D model of the AR ligand-binding domain (AR LBD) has
      been added to give a better understanding of gene structure-function
      relationships. In addition, silent mutations have now been reported in both
      androgen insensitivity syndrome (AIS) and prostate cancer (CaP) cases. The
      database also now incorporates information on the exon 1 CAG repeat expansion
      disease, spinobulbar muscular atrophy (SBMA), as well as CAG repeat length
      variations associated with risk for female breast, uterine endometrial,
      colorectal, and prostate cancer, as well as for male infertility. The possible
      implications of somatic mutations, as opposed to germline mutations, in the
      development of future locus-specific mutation databases (LSDBs) is discussed. The
      database is available on the Internet (http://www.mcgill.ca/androgendb/).

PMID- 15146456
TI  - PromoLign: a database for upstream region analysis and SNPs.
AB  - The study of transcriptional regulation at the genomic level has been hindered by
      the lack of functional annotation in the putative regulatory regions.
      Phylogenetic footprinting, in which cross-species sequence alignment among
      orthologous genes is applied to locate conserved sequence blocks, is an effective
      strategy to attack this problem. Single nucleotide polymorphisms (SNPs) in
      transcription factor (TF) binding sites contribute to the heterogeneity of TF
      binding sites and might disrupt or enhance their regulatory activity. The
      correlation of SNPs with the TF sites will not only help in functional evaluation
      of SNPs, but will also help in the study of transcription regulation by focusing
      attention on specific TF sites. PromoLign
      (http://polly.wustl.edu/promolign/main.html) is an online database application
      that presents SNPs and TF binding profiles in the context of human-mouse
      orthologous sequence alignment with a hyperlinked graphical interface. PromoLign
      could be applied to a variety of SNPs and transcription related studies,
      including association genetics, population genetics, and pharmacogenetics.

PMID- 15146458
TI  - Identification of a functional mutation in pp32r1 (ANP32C).
AB  - No mutations or polymorphisms have previously been reported in pp32r1 (ANP32C;
      GenBank: AF008216.1). pp32r1 is part of the highly conserved ANP32 family, some
      of whose members are associated with control of histone acetylation, mRNA
      stability, and specialized forms of apoptosis. Although 87.6% identical at the
      protein level, pp32r1 is functionally distinct from pp32 (ANP32A) in its failure
      to suppress oncogenesis in in vitro transformation systems and its tumorigenicity
      in in vivo assays. The present study found that pp32r1 expression levels vary
      among human tumor cell lines, with the highest levels found in prostatic
      adenocarcinoma cell lines. pp32r1 also appears to be polymorphic at nucleotide
      g.4520 and nucleotide g.4664 in human tobacco-associated oral mucosal lesions,
      human fibroblast cell lines, and several carcinoma cell lines. PC-3 human
      prostatic adenocarcinoma cells likewise appear to be polymorphic at these loci,
      but additionally contain a g.4870T>C transversion mutation. The mutation results
      in a p.Tyr140His substitution, which lies in a functionally important region of
      the molecule. In the PC-3 prostate cancer line, the mutation is either
      homozygous, or hemizygous accompanied by loss of heterozygosity. ACHN cells
      stably transfected with pp32r1 containing this mutation showed a markedly
      increased rate of growth. The pp32r1 mutation could thus be causally associated
      with the neoplastic growth properties of PC-3, and be of potential clinical
      significance.

PMID- 15146457
TI  - Identification and characterization of ANKK1: a novel kinase gene closely linked
      to DRD2 on chromosome band 11q23.1.
AB  - The dopamine D2 receptor has been extensively studied in relation to alcoholism,
      substance abuse, and nicotine dependence. The most frequently examined
      polymorphism linked to this gene is the Taq1A restriction fragment length
      polymorphism (RFLP) (dbSNP rs1800497; g.32806C>T in GenBank AF050737.1), which
      has been associated with a reduction in D2 receptor density, although this is not
      universally accepted. The Taq1A RFLP lies 10 kB downstream of DRD2 and may
      therefore fall within a different coding region than the DRD2 gene or within a
      regulatory region. Within this downstream region, we have identified a novel
      kinase gene, named ankyrin repeat and kinase domain containing 1 (ANKK1), which
      contains a single serine/threonine kinase domain and is expressed at low levels
      in placenta and whole spinal cord RNA. This gene is a member of an extensive
      family of proteins involved in signal transduction pathways. The DRD2 Taq1A RFLP
      is a single nucleotide polymorphism (SNP) that causes an amino acid substitution
      within the 11th ankyrin repeat of ANKK1 (p.Glu713Lys), which, while unlikely to
      affect structural integrity, may affect substrate-binding specificity. If this is
      the case, then changes in ANKK1 activity may provide an alternative explanation
      for previously described associations between the DRD2 Taq1A RFLP and
      neuropsychiatric disorders such as addiction.

PMID- 15146459
TI  - Identification of a new complementation group of the peroxisome biogenesis
      disorders and PEX14 as the mutated gene.
AB  - Peroxisome biogenesis disorders (PBD) are lethal hereditary diseases caused by
      abnormalities in the biogenesis of peroxisomes. At present, 12 different
      complementation groups have been identified and to date, all genes responsible
      for each of these complementation groups have been identified. The peroxisomal
      membrane protein PEX14 is a key component of the peroxisomal import machinery and
      may be the initial docking site for the two import receptors PEX5 and PEX7.
      Although PEX14 mutants have been identified in yeasts and CHO-cells, human PEX14
      deficiency has apparently not been documented. We now report the identification
      of a new complementation group of the peroxisome biogenesis disorders with PEX14
      as the defective gene. Indeed, human PEX14 rescues the import of a PTS1-dependent
      as well as a PTS2-dependent protein into the peroxisomes in fibroblasts from a
      patient with Zellweger syndrome belonging to the new complementation group. This
      patient was homozygous for a nonsense mutation in a putative coiled-coil region
      of PEX14, c.553C>T (p.Q185X). Furthermore, we showed that the patient's
      fibroblasts lacked PEX14 as determined by immunocytochemical analysis. These
      findings indicate that there are 13 genotypes in PBD and that the role of PEX14
      is also essential in humans.

PMID- 15146460
TI  - Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH)
      identified in patients with mucopolysaccharidosis type III A.
AB  - Mucopolysaccharidosis type IIIA (MPSIIIA) is an autosomal recessive lysosomal
      storage disease caused by mutations in the N-sulfoglucosamine sulfohydrolase gene
      (SGSH; encoding sulfamidase, also sulphamidase) leading to the lysosomal
      accumulation and urinary excretion of heparan sulfate. Considerable variation in
      the onset and severity of the clinical phenotype is observed. We report here on
      expression studies of four novel mutations: c.318C>A (p.Ser106Arg), c.488T>C
      (p.Leu163Pro), c.571G>A (p.Gly191Arg), and c.1207_1209delTAC (p.Tyr403del), and
      five previously known mutations: c.220C>T (p.Arg74Cys), c.697C>T (p.Arg233X),
      c.1297C>T (p.Arg433Trp), c.1026dupC (p.Leu343fsX158), and c.1135delG
      (p.Val379fsX33) identified in MPSIIIA patients. Transient expression of mutant
      sulfamidases in BHK or CHO cells revealed that all the mutants were enzymatically
      inactive with the exception of c.318C>A (p.Ser106Arg), which showed 3.3% activity
      of the expressed wild-type enzyme. Western blot analysis demonstrated that the
      amounts of expressed mutant sulfamidases were significantly reduced compared with
      cells expressing wild type. No polypeptides were immunodetectable in extracts of
      cells transfected with the cDNA carrying the c.697C>T (p.Arg233X) nonsense
      mutation. In vitro translation and pulse-chase experiments showed that rapid
      degradation rather than a decrease in synthesis is responsible for the low,
      steady-state level of the mutant proteins in cells. The amounts of secreted
      mutant precursor forms, the cellular stability, the proteolytic processing, and
      data from double-label immunofluorescence microscopy suggest that the degradation
      of the majority of newly synthesized c.220C>T (p.Arg74Cys), c.571G>A
      (p.Gly191Arg), c.1297C>T (p.Arg433Trp), c.1026dupC (p.Leu343fsX158), and
      c.1135delG (p.Val379fsX33) mutant proteins probably occurs in the ER, whereas
      c.488T>C (p.Leu163Pro) mutant protein showed instability in the lysosomes.

PMID- 15146461
TI  - Functional analysis of 13 GBA mutant alleles identified in Gaucher disease
      patients: Pathogenic changes and "modifier" polymorphisms.
AB  - Gaucher disease, the most prevalent sphingolipidosis, is caused by the deficient
      activity of acid beta-glucosidase, mainly due to mutations in the GBA gene. Over
      200 mutations have been identified worldwide, more than 25 of which were in
      Spanish patients. In order to demonstrate causality for Gaucher disease, some of
      them: c.662C>T (p.P182L), c.680A>G (p.N188S), c.886C>T (p.R257X), c.1054T>C
      (p.Y313H), c.1093G>A (p.E326K), c.1289C>T (p.P391L), c.1292A>T (p.N392I),
      c.1322T>C (p.I402T), and the double mutants [c.680A>G; c.1093G>A] ([p.N188S;
      p.E326K]) and [c.1448T>C; c.1093G>A] ([p.L444P; p.E326K]), were expressed in Sf9
      cells using a baculovirus expression system. Other well-established Gaucher
      disease mutations, namely c.1226A>G (p.N370S), c.1342G>C (p.D409H), and c.1448T>C
      (p.L444P), were also expressed for comparison. The levels of residual acid beta
      glucosidase activity of the mutant enzymes produced by the cDNAs carrying alleles
      c.662C>T (p.P182L), c.886C>T (p.R257X), c.1054T>C (p.Y313H), c.1289C>T (p.P391L),
      and c.1292A>T (p.N392I) were negligible. The c.1226A>G (p.N370S), c.1322T>C
      (p.I402T), c.1342G>C (p.D409H), c.1448T>C (p.L444P), and [c.1448T>C; c.1093G>A]
      ([p.L444P; p.E326K]) alleles produced enzymes with levels ranging from 6 to 14%
      of the wild-type. The three remaining alleles, c.680A>G (p.N188S), c.1093G>A
      (p.E326K), and [c.680A>G; c.1093G>A] ([p.N188S; p.E326K]), showed higher activity
      (66.6, 42.7, and 23.2%, respectively). Expression studies revealed that the
      c.1093G>A (p.E326K) change, which was never found alone in a Gaucher disease
      causing allele, when found in a double mutant such as [c.680A>G; c.1093G>A]
      ([p.N188S; p.E326K]) and [c.1448T>C; c.1093G>A] ([p.L444P; p.E326K]), decreases
      activity compared to the activity found for the other mutation alone. These
      results suggest that c.1093G>A (p.E326K) should be considered a "modifier
      variant" rather than a neutral polymorphism, as previously considered. Mutation
      c.680A>G (p.N188S), which produces a mutant enzyme with the highest level of
      activity, is probably a very mild mutation or another "modifier variant."

PMID- 15146462
TI  - Molecular and functional analysis of SUMF1 mutations in multiple sulfatase
      deficiency.
AB  - Multiple sulfatase deficiency (MSD) is a rare disorder characterized by impaired
      activity of all known sulfatases. The gene mutated in this disease is SUMF1,
      which encodes a protein involved in a post-translational modification at the
      catalytic site of all sulfatases that is necessary for their function. SUMF1
      strongly enhances the activity of sulfatases when coexpressed with sulfatase in
      Cos-7 cells. We performed a mutational analysis of SUMF1 in 20 MSD patients of
      different ethnic origin. The clinical presentation of these patients was
      variable, ranging from severe neonatal forms to mild phenotypes showing mild
      neurological involvement. A total of 22 SUMF1 mutations were identified,
      including missense, nonsense, microdeletion, and splicing mutations. We expressed
      all missense mutations in culture to study their ability to enhance the activity
      of sulfatases. Of the predicted amino acid changes, 11 (p.R349W, p.R224W, p.L20F,
      p.A348P, p.S155P, p.C218Y, p.N259I, p.A279V, p.R349Q, p.C336R, p.A177P) resulted
      in severely impaired sulfatase-enhancing activity. Two (p.R345C and p.P266L)
      showed a high residual activity on some, but not all, of the nine sulfatases
      tested, suggesting that some SUMF1 mutations may have variable effects on the
      activity of each sulfatase. This study compares, for the first time, clinical,
      biochemical, and molecular data in MSD patients. Our results show lack of a
      direct correlation between the type of molecular defect and the severity of
      phenotype.

PMID- 15146463
TI  - Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic
      consequences.
AB  - EYA1 mutations cause branchio-oto-renal (BOR) syndrome. These mutations include
      single nucleotide transitions and transversions, small duplications and
      deletions, and complex genomic rearrangements. The last cannot be detected by
      coding sequence analysis of EYA1. We sought to refine the clinical diagnosis of
      BOR syndrome by analyzing phenotypic data from families segregating EYA1 disease
      causing mutations. Based on genotype-phenotype analyses, we propose new criteria
      for the clinical diagnosis of BOR syndrome. We found that in approximately 40% of
      persons meeting our criteria, EYA1 mutations were identified. Of these mutations,
      80% were coding sequence variants identified by SSCP, and 20% were complex
      genomic rearrangements identified by a semiquantitative PCR-based screen. We
      conclude that genetic testing of EYA1 should include analysis of the coding
      sequence and a screen for complex rearrangements.

PMID- 15146464
TI  - General implications for CpG hot spot mutations: methylation patterns of the
      human iduronate-2-sulfatase gene locus.
AB  - The methylation pattern at CpG sites of a housekeeping gene correlates with the
      likelihood of mutation. Mucopolysaccharidosis (MPS) type II, an X-linked
      disorder, results from the deficiency of iduronate-2-sulfatase (IDS). In these
      patients, over 35% of independent point mutations at the IDS gene locus were
      found at CpG sites as transitional events. To gain insight into the relationship
      between methylation status and CpG hot spot mutations, we investigated patterns
      of cytosine methylation in the entire IDS gene, except for introns 4-8. Bisulfite
      genomic sequencing was performed on the normal leukocyte DNA. Our data show that:
      1) cytosine methylation at the CpG sites was extensive, except for those present
      from the promoter region to a portion of intron 3; 2) a sharp boundary of
      methylated-nonmethylated regions was observed at the 5'-flanking region, whereas
      a gradual change in methylation was observed in the 2.0-kb segment in the 3'
      flanking region; 3) the boundary of the 5'-flanking region contained multiple Sp1
      sites and the TATA box; 4) the CpG sites in exons 1 and 2 were hypomethylated and
      were associated only with rare transitional mutations, while the CpG sites in
      exon 3 were also hypomethylated, yet were associated with a high rate of
      transitional mutations; 5) there was no striking sex difference in the
      methylation patterns in active alleles; and, 6) the methylation in both strands
      was symmetrical, except at the boundary of methylated-unmethylated regions.

PMID- 15146465
TI  - Structural and functional analysis of mutations at the human hypoxanthine
      phosphoribosyl transferase (HPRT1) locus.
AB  - Hypoxanthine phosphoribosyl transferase (HPRT, also known as HGPRT) is an often
      used genetic marker in eukaryotic cells. The gene is conserved from bacteria to
      human, with retained catalytic activity, although substrate specificity may have
      changed, and the enzyme is essential in malaria-causing protozoans. Inherited
      mutations in the human HPRT1 gene result in three different phenotypes: Lesch
      Nyhan syndrome (LNS or LND), LND variants, and HPRT-related hyperuricemia (HRH).
      In cultured cells, loss of HPRT activity gives rise to 6-thioguanine (6-TG)
      resistance. In general, cells from LND patients are also 6-TG resistant, whereas
      cells from HRH patients are not, with some interesting exceptions. Using modeling
      methods, we have studied the correlation between the mutable and nonmutated amino
      acid residues on one hand, and sequence conservation and predicted phenotypic
      effects on the other hand. Our results demonstrate that most of the mutations are
      explainable by the predicted effect on protein structure and function. They are
      also consistent with sequence conservation. Moreover, the mutational profiles of
      TG-resistant cells and LND overlap to a great extent, while most of the mutations
      in HRH are unique to that condition. We have also noticed a strong correlation
      between mutations in the tetramer interfaces and observed phenotypes, suggesting
      a functional role for a tetramer transition during catalysis.

PMID- 15146466
TI  - Denaturing high-performance liquid chromatography (DHPLC) as a reliable high
      throughput prescreening method for aberrant promoter methylation in cancer.
AB  - Aberrant promoter hypermethylation of CpG dinucleotides is a frequent and
      significant mechanism of tumor suppressor gene (TSG) silencing in cancer. As
      increasing numbers of downregulated putative TSGs are emerging from large-scale
      expression profiling studies, high-throughput techniques are needed to screen for
      hypermethylation. DHPLC has been established as a reliable, highly sensitive
      technique for mutation analysis. In this study, the use of DHPLC as a
      prescreening method for the identification of CpG methylation was developed by
      analyzing DNA samples with different, well-characterized methylation patterns of
      the CDKN2A/p16 promoter. Bisulfite treatment of genomic DNA was followed by PCR
      amplification of unmethylated as well as methylated CDKN2A/p16 promoter
      sequences. PCR products were denatured and renatured, permitting the formation of
      heteroduplex DNA detectable by DHPLC. Methylation of all CpG-sites results in a
      single peak (homoduplex) with a shift in retention time, whereas partial
      methylation can be recognized by additional signals representing diverse
      heteroduplex structures. After method development, 35 DNA samples from primary
      bladder and breast carcinomas were analyzed in a blinded fashion, revealing
      complete or partial methylation of the p16 promoter in eight cases and a
      heterozygous mutation in one case. In conclusion, DHPLC is a highly sensitive and
      convenient method for methylation screening.

PMID- 15146467
TI  - An improved electronic microarray-based diagnostic assay for identification of
      MEFV mutations.
AB  - Recent technological advances, such as DNA chip devices that allow automated,
      high-throughput genotyping, promise to considerably improve the detection
      capability of single-nucleotide polymorphisms (SNPs) in clinically relevant
      genes. We used the NanoChip(R) Molecular Biology Workstation (Nanogen,
      www.nanogen.com) and recently introduced microelectronic array technology to
      develop a detection method for the more frequent mutations involved in familial
      Mediterranean fever (FMF), an autosomal recessive disease that affects several
      ethnic groups in the Mediterranean population, whose early diagnosis is crucial
      if severe complications are to be prevented. We adapted the previously described
      Nanogen procedures to FMF mutation analysis, introducing modifications that
      notably improve the technique. First, as the original procedure makes use of
      costly dye-tagged reporter sequences, we devised a universal reporter strategy,
      which was first evaluated and validated on the robust, previously established
      factor V Leiden and factor II (prothrombin) NanoChip diagnostic assays. FMF
      (MEFV), factor V (F5), and factor II (F2) genotypes identified using this
      improved system were totally concordant with results of other genotyping methods
      (denaturing gradient gel electrophoresis [DGGE], SSCP, and RFLP analysis).
      Second, we showed that the target sequences loaded on the NanoChip cartridges can
      be rehybridized several times in a highly reproducible manner, allowing
      sequential analysis of mutations. Thus, we devised a strategy that allows us to
      monitor the possible interference of additional mutations or SNPs at probe or
      stabilizer sequences. Finally, a comparative cost per sample analysis
      demonstrates that the accurate and reproducible FMF mutation detection assay we
      developed can be readily implemented in the clinical laboratory setting at
      reasonable expense.

PMID- 15146469
TI  - Novel and recurrent mutations in the NF1 gene in Italian patients with
      neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant
      disorders in humans, affecting 1 in 3500 individuals. NF1 is a fully penetrant
      exhibiting a mutation rate some 10-fold higher compared to most other disease
      genes. As a consequence, a high number of cases (up to 50%) are sporadic.
      Mutation detection is complex due to the large size of NF1 gene, the presence of
      pseudogenes and the great variety of lesions. In the present study we attempted
      to delineate the NF1 mutational spectrum in the Italian population reporting four
      year experience with the direct analysis of the whole NF1 coding region in 110
      unrelated subjects affected by NF1. For each patient, the whole coding sequence
      and all splice sites were studied for mutations, either by the protein truncation
      test (PTT), or, most often, by denaturing high performance liquid chromatography
      (DHPLC). Mutations were identified in 75 (68%) patients. Twenty-two mutations
      were found to be novel. The detection rate for the different methods was 7/18
      (39%) for PTT, and 68/103 (66%) for DHPLC. The mutations were evenly distributed
      along the NF1 coding sequence. Thirty-two of the 75 unrelated NF1 patients in
      which germline mutations were identified (32/75, 43%) harbour 23 different
      recurrent mutations. Fifteen sequence variants likely to represent non-pathogenic
      polymorphisms were observed at the NF1 locus. Genotype-phenotype analysis was
      unable to detect any obvious correlation.

PMID- 15146470
TI  - Seven novel mutations of the ADAR gene in Chinese families and sporadic patients
      with dyschromatosis symmetrica hereditaria (DSH).
AB  - Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary
      genodermatosis characterized by hyperpigmented and hypopigmented macules of on
      the extremities and caused by the mutations in the ADAR gene(also called DSRAD)
      encoding for RNA-specific adenosine deaminase. Here we reported clinical and
      molecular findings of 6 Chinese multi-generation families and 2 sporadic patients
      with DSH. We found that the same mutation could lead to different phenotypes even
      in the same family and we did not establish a clear correlation between genotypes
      and phenotypes. Seven novel heterozygous mutations of ADAR were identified, which
      were c.2433_2434delAG (p.T811fs), c.2197G>T (p.E733X), c.3286C>T (p.R1096X),
      c.2897G>T (p.C966F), c.2797C>T (p.Q933X), c.2375delT (p.L792fs) and c.3203-2A>G
      respectively. Our data add new variants to the repertoire of ADAR mutations in
      DSH.

PMID- 15146471
TI  - Familial melanoma, pancreatic cancer and germline CDKN2A mutations.
AB  - Germline CDKN2A mutations have been observed in approximately 20 percent of
      familial melanoma kindreds from North America, Europe and Australasia. There is
      also an increased risk of pancreatic cancer in a subset of families with
      mutations, however, the precise relationship between the CDKN2A gene and
      pancreatic cancer remains unknown. The relationships between familial melanoma,
      pancreatic cancer and germline CDKN2A mutations were examined using published
      data. There were 67 different CDKN2A mutations in 189 melanoma-prone families.
      Forty-two families (18 mutations) had pancreatic cancer reported. For families
      without reported pancreatic cancer, the most common types of mutations were
      missense (56%), frameshift (12%), and deletions (12%). For families with
      pancreatic cancer, missense (56%), splicing (17%), and frameshift (11%) mutations
      were most common. Seventy percent of the mutations were observed only once, while
      the remainder recurred in different families. Comparison of 147 melanoma-prone
      families without pancreatic cancer to the 42 families that had pancreatic cancer
      reported showed no significant differences in the types or locations of
      mutations. However, there was a significant difference (p=0.002) in the
      distribution of families across the four ankyrin repeats. This finding primarily
      resulted from the six most frequent mutations where the distribution of
      pancreatic cancer varied significantly (p=0.02) from at least 30% in c.301G>T
      (p.G101W), c.225_243del19 (p.P75fs), c.337_338insGTC (p.R112_L113insR), and
      c.377T>A (p.V126D) families to less than 10% in c.71G>C (p.R24P) and c.159G>C
      (p.M53I) families. Further research utilizing individual-specific data will be
      required to determine whether these patterns represent etiologic differences or
      incomplete reporting of cancer and mutation data.

PMID- 15146472
TI  - Detection of 53 novel DNA variations within the tyrosinase gene and accumulation
      of mutations in 17 patients with albinism.
AB  - Oculocutaneous albinism (OCA) in man may be caused by mutations within the
      tyrosinase gene (TYR) resulting in OCA1. Analysing patients with recessively
      inherited albinism we found DNA variations in 82 unrelated individuals. 53 out of
      78 mutations and polymorphisms revealed by this study are not published
      previously. The changes include 68 nucleotide substitutions resulting in amino
      acid changes, stop mutations and polymorphisms as well as four nucleotide
      insertions and six deletions. Furthermore, we found an accumulation of three to
      five mutations in 17 patients with OCA1.

PMID- 15146473
TI  - Identification and functional analysis of two novel mutations in the CBS gene in
      Polish patients with homocystinuria.
AB  - Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is an
      inherited disorder of homocysteine transsulfuration, which manifests by
      neurological, vascular and connective tissue involvement. So far, 130 pathogenic
      mutations have been recognized in the CBS gene. We examined 10 independent
      alleles in Polish patients suffering from CBS deficiency, and we detected four
      already described mutations (c.1224-2A>C, c.684C>A, c.833T>C, and c.442G>A) and
      two novel mutations (c.429C>G and c.1039+1G>T). The pathogenicity of the novel
      mutations was demonstrated by expression in E.coli. This is the first published
      communication on mutations leading to CBS deficiency in Poland.

PMID- 15146474
TI  - GJB2 mutations in patients with non-syndromic hearing loss from Northeastern
      Hungary.
AB  - Mutations in the GJB2 gene encoding the gap-junction protein connexin 26 have
      been identified in many patients with childhood hearing impairment (HI). One
      single mutation, c.35delG, accounts for the majority of mutations in Caucasian
      patients with HI. In the present study we screened 500 healthy control
      individuals and a group of patients with HI from Northeastern Hungary for GJB2
      mutations. The patients' group consisted of 102 familial from 28 families and 92
      non-familial cases. The most common mutation in the Hungarian population is the
      c.35delG, followed by the c.71G>A (p.W24X) mutation. 34.3% of the patients in the
      familial group were homozygous, and 17.6% heterozygous for 35delG. In the non
      familial group the respective values were 37% and 18% (allele frequency: 46.2%).
      In the general population an allele frequency of 2.4% was determined. Several
      patients were identified with additional, already described or new GJB2
      mutations, mostly in heterozygous state. The mutation c.380G>A (p.R127H) was
      formerly found only in heterozygous state and its disease relation was
      controversial. We demonstrated the presence of this mutation in a family with
      three homozygous patients and 4 heterozygous unaffected family members, a clear
      indication of recessively inherited HI. Furthermore, we provided evidence for the
      pathogenic role of two new mutations, c.51C>A (p.S17Y) and c.177G>T (p.G59V),
      detected in the present study. In the latter case the pattern of inheritance
      might be dominant. Our results confirm the importance of GJB2 mutations in the
      Hungarian population displaying mutation frequencies that are comparable with
      those in the Mediterranean area.

PMID- 15146475
TI  - BMPR2 mutations found in Japanese patients with familial and sporadic primary
      pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH) is a potentially lethal disorder, in which
      heterozygous mutations within the bone morphogenetic protein type II receptor
      (BMPR2) gene (BMPR2) have been identified. We conducted a molecular study of
      BMPR2 mutations in 4 Japanese families with familial PPH and 30 Japanese patients
      with sporadic PPH, and found 13 different mutations, of which 10 were novel,
      including missense (n=2), nonsense (n=4), frameshift (n=3), and splice-donor site
      (n=1) mutations. In total, BMPR2 mutations were found in all 4 familial PPH cases
      and 12 (40%) of the sporadic PPH cases. Further, a majority of the mutations
      found were predicted to cause premature termination, as previously reported. In
      the 9 mutations found in the sporadic cases, 2 were shown to be de novo, 2 were
      shared in multiple cases, 1 was shared with an FPPH case, and 1 was the same as
      previously reported in Caucasian FPPH. These results indicate that a substantial
      portion of Japanese PPH patients carry BMPR2 mutations with considerable
      heterogeneity.

PMID- 15146476
TI  - Novel GNE mutations in Italian families with autosomal recessive hereditary
      inclusion-body myopathy.
AB  - The most common form of autosomal recessive (AR) hereditary inclusion-body
      myopathy (HIBM), originally described in Persian-Jewish families, is
      characterized by onset in early adult life with weakness and atrophy of distal
      lower limb muscles, which progress proximally and relatively spare the
      quadriceps. AR HIBM is associated with mutations in the UDP-N-acetylglucosamine 2
      epimerase/N-acetylmannosamine kinase gene (GNE) on chromosome 9p12-13. In the
      present study we have identified seven novel GNE mutations in patients from five
      unrelated Italian families with clinical and pathologic features indicative of AR
      HIBM. Four were missense mutations (c.1556A>G [p.N519S], c.79C>T [p.P27S],
      c.1798G>A [p.A600T] and c.616G>A [p.G206S]), two consisted in a single-base
      deletion (c.616delG [p.G206fsX4] and c.1130delT [p.I377fsX16]) and one in an
      intronic single-base insertion (c.1070+2dupT). These latter findings further
      extend the type of GNE mutations associated with HIBM. Furthermore, in one
      patient we also identified the c.737G>A [p.R246Q] missense mutation that
      corresponds to the one previously reported in a family from the Bahamas.
      Interestingly, in two of our families distinct mutations affected nucleotide
      c.616 in exon 3 (c.616delG and c.616G>A). The possibility of specific portions of
      the gene being more prone to mutations remains to be elucidated.

PMID- 15146477
TI  - Crystal structure of a protein associated with cell division from Mycoplasma
      pneumoniae (GI: 13508053): a novel fold with a conserved sequence motif.
AB  - UPF0040 is a family of proteins implicated in a cellular function of bacteria
      cell division. There is no structure information available on protein of this
      family. We have determined the crystal structure of a protein from Mycoplasma
      pneumoniae that belongs to this family using X-ray crystallography. Structural
      homology search reveals that this protein has a novel fold with no significant
      similarity to any proteins of known three-dimensional structure. The crystal
      structures of the protein in three different crystal forms reveal that the
      protein exists as a ring of octamer. The conserved protein residues, including a
      highly conserved DXXXR motif, are examined on the basis of crystal structure.

PMID- 15146478
TI  - Ultrahigh resolution drug design I: details of interactions in human aldose
      reductase-inhibitor complex at 0.66 A.
AB  - The first subatomic resolution structure of a 36 kDa protein [aldose reductase
      (AR)] is presented. AR was cocrystallized at pH 5.0 with its cofactor NADP+ and
      inhibitor IDD 594, a therapeutic candidate for the treatment of diabetic
      complications. X-ray diffraction data were collected up to 0.62 A resolution and
      treated up to 0.66 A resolution. Anisotropic refinement followed by a blocked
      matrix inversion produced low standard deviations (<0.005 A). The model was very
      well ordered overall (CA atoms' mean B factor is 5.5 A2). The model and the
      electron-density maps revealed fine features, such as H-atoms, bond densities,
      and significant deviations from standard stereochemistry. Other features, such as
      networks of hydrogen bonds (H bonds), a large number of multiple conformations,
      and solvent structure were also better defined. Most of the atoms in the active
      site region were extremely well ordered (mean B approximately 3 A2), leading to
      the identification of the protonation states of the residues involved in
      catalysis. The electrostatic interactions of the inhibitor's charged carboxylate
      head with the catalytic residues and the charged coenzyme NADP+ explained the
      inhibitor's noncompetitive character. Furthermore, a short contact involving the
      IDD 594 bromine atom explained the selectivity profile of the inhibitor,
      important feature to avoid toxic effects. The presented structure and the details
      revealed are instrumental for better understanding of the inhibition mechanism of
      AR by IDD 594, and hence, for the rational drug design of future inhibitors. This
      work demonstrates the capabilities of subatomic resolution experiments and
      stimulates further developments of methods allowing the use of the full potential
      of these experiments.

PMID- 15146479
TI  - Ultrahigh resolution drug design. II. Atomic resolution structures of human
      aldose reductase holoenzyme complexed with Fidarestat and Minalrestat:
      implications for the binding of cyclic imide inhibitors.
AB  - The X-ray structures of human aldose reductase holoenzyme in complex with the
      inhibitors Fidarestat (SNK-860) and Minalrestat (WAY-509) were determined at
      atomic resolutions of 0.92 A and 1.1 A, respectively. The hydantoin and
      succinimide moieties of the inhibitors interacted with the conserved anion
      binding site located between the nicotinamide ring of the coenzyme and active
      site residues Tyr48, His110, and Trp111. Minalrestat's hydrophobic isoquinoline
      ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219,
      with the bromo-fluorobenzyl group inside the "specificity" pocket. The
      interactions between Minalrestat's bromo-fluorobenzyl group and the enzyme
      include the stacking against the side-chain of Trp111 as well as hydrogen bonding
      distances with residues Leu300 and Thr113. The carbamoyl group in Fidarestat
      formed a hydrogen bond with the main-chain nitrogen atom of Leu300. The atomic
      resolution refinement allowed the positioning of hydrogen atoms and accurate
      determination of bond lengths of the inhibitors, coenzyme NADP+ and active-site
      residue His110. The 1'-position nitrogen atom in the hydantoin and succinimide
      moieties of Fidarestat and Minalrestat, respectively, form a hydrogen bond with
      the Nepsilon2 atom of His 110. For Fidarestat, the electron density indicated two
      possible positions for the H-atom in this bond. Furthermore, both native and
      anomalous difference maps indicated the replacement of a water molecule linked to
      His110 by a Cl-ion. These observations suggest a mechanism in which Fidarestat is
      bound protonated and becomes negatively charged by donating the proton to His110,
      which may have important implications on drug design.

PMID- 15146480
TI  - Virtual screening for inhibitors of human aldose reductase.
AB  - The inhibition of aldose reductase (AR) provides an interesting strategy to
      prevent the complications of chronic diabetes. Although a large number of
      different AR inhibitors are known, very few of these compounds exhibit sufficient
      efficacy in clinical trials. We performed a virtual screening based on the
      ultrahigh resolution crystal structure of the inhibitor IDD594 in complex with
      human AR. AR operates on a large scale of structurally different substrates. To
      achieve this pronounced promiscuity, the enzyme can adapt rather flexibly to its
      substrates. Likewise, it has a similar adaptability for the binding of
      inhibitors. We applied a protocol of consecutive hierarchical filters to search
      the Available Chemicals Directory. In the first selection step, putative ligands
      were chosen that exhibit functional groups to anchor the anion-binding pocket of
      AR. Subsequently, a pharmacophore model based on the binding geometry of IDD594
      and the mapping of the binding pocket in terms of putative "hot spots" of binding
      was applied as a second consecutive filter. In a third and final filtering step,
      the remaining candidate molecules were flexibly docked into the binding pocket of
      IDD594 with FlexX and ranked according to their estimated DrugScore values. Out
      of 206 compounds selected by this search and complemented by a cluster analysis
      and visual inspection, 9 compounds were selected and subjected to biological
      testing. Of these, 6 compounds showed IC50 values in the micromolar range.
      According to the proposed binding mode, the two inhibitors BTB02809 (IC50 = 2.4
      +/- 0.5 microM) and JFD00882 (IC50 = 4.1 +/- 1.0 microM) both place a nitro group
      into the hydrophobic specificity pocket of human AR in an orientation coinciding
      with the position of the bromine atom of IDD594. The interaction of this Br with
      Thr113 has been identified as a key feature that is responsible for selectivity
      enhancement.

PMID- 15146481
TI  - An unusual triosephosphate isomerase from the early divergent eukaryote Giardia
      lamblia.
AB  - Recombinant triosephosphate isomerase from the parasite Giardia lamblia (GlTIM)
      was characterized and immunolocalized. The enzyme is distributed uniformly
      throughout the cytoplasm. Size exclusion chromatography of the purified enzyme
      showed two peaks with molecular weights of 108 and 55 kDa. Under reducing
      conditions, only the 55-kDa protein was detected. In denaturing gel
      electrophoresis without dithiothreitol, the enzyme showed two bands with
      molecular weights of 28 and 50 kDa; with dithiotretitol, only the 28-kDa protein
      was observed. These data indicate that GlTIM may exist as a tetramer or a dimer
      and that, in the former, the two dimers are covalently linked by disulfide bonds.
      The kinetics of the dimer were similar to those of other TIMs. The tetramer
      exhibited half of the kcat of the dimer without changes in the Km. Studies on the
      thermal stability and the apparent association constants between monomers showed
      that the tetramer was slightly more stable than the dimer. This finding suggests
      the oligomerization is not related to enzyme thermostability as in Thermotoga
      maritima. Instead, it could be that oligomerization is related to the regulation
      of catalytic activity in different states of the life cycle of this mesophilic
      parasite.

PMID- 15146482
TI  - Solution structure of BmKK2, a new potassium channel blocker from the venom of
      chinese scorpion Buthus martensi Karsch.
AB  - A natural K+ channel blocker, BmKK2 (a member of scorpion toxin subfamily alpha
      KTx 14), which is composed of 31 amino acid residues and purified from the venom
      of the Chinese scorpion Buthus martensi Karsch, was characterized using whole
      cell patch-clamp recording in rat hippocampal neurons. The three dimensional
      structure of BmKK2 was determined with two-dimensional NMR spectroscopy and
      molecular modelling techniques. In solution this toxin adopted a common
      alpha/beta-motif, but showed distinct local conformation in the loop between
      alpha-helix and beta-sheet in comparison with typical short-chain scorpion toxins
      (e.g., CTX and NTX). Also, the alpha helix is shorter and the beta-sheet element
      is smaller (each strand consisted only two residues). The unusual structural
      feature of BmKK2 was attributed to the shorter loop between the alpha-helix and
      beta-sheet and the presence of two consecutive Pro residues at position 21 and 22
      in the loop. Moreover, two models of BmKK2/hKv1.3 channel and BmKK2/rSK2 channel
      complexes were simulated with docking calculations. The results demonstrated the
      existence of a alpha-mode binding between the toxin and the channels. The model
      of BmKK2/rSK2 channel complex exhibited favorable contacts both in electrostatic
      and hydrophobic, including a network of five hydrogen bonds and bigger interface
      containing seven pairs of inter-residue interactions. In contrast, the model of
      BmKK2/hKv1.3 channel complex, containing only three pairs of inter-residue
      interactions, exhibited poor contacts and smaller interface. The results well
      explained its lower activity towards Kv channel, and predicted that it may prefer
      a type of SK channel with a narrower entryway as its specific receptor.

PMID- 15146483
TI  - Sequence and structure of epoxide hydrolases: a systematic analysis.
AB  - Epoxide hydrolases (EC 3.3.2.3) are ubiquitous enzymes that catalyze the
      hydrolysis of epoxides to the corresponding vicinal diols. More than 100 epoxide
      hydrolases (EH) have been identified or predicted, and 3 structures are
      available. Although they catalyze the same chemical reaction, sequence similarity
      is low. To identify conserved regions, all EHs were aligned. Phylogenetic
      analysis identified 12 homologous families, which were grouped into 2 major
      superfamilies: the microsomal EH superfamily, which includes the homologous
      families of Mammalian, Insect, Fungal, and Bacterial EHs, and the cytosolic EH
      superfamily, which includes Mammalian, Plant, and Bacterial EHs. Bacterial EHs
      show a high sequence diversity. Based on structure comparison of three known
      structures from Agrobacterium radiobacter AD1 (cytosolic EH), Aspergillus niger
      (microsomal EH), Mus musculus (cytosolic EH), and multisequence alignment and
      phylogenetic analysis of 95 EHs, the modular architecture of this enzyme family
      was analyzed. Although core and cap domain are highly conserved, the structural
      differences between the EHs are restricted to only two loops: the NC-loop
      connecting the core and the cap and the cap-loop, which is inserted into the cap
      domain. EHs were assigned to either of three clusters based on loop length. By
      using this classification, core and cap region of all EHs, NC-loops and cap-loops
      of 78% and 89% of all EHs, respectively, could be modeled. Representative models
      are available from the Lipase Engineering Database, http://www.led.uni
      stuttgart.de.

PMID- 15146484
TI  - Pex5p binding affinities for canonical and noncanonical PTS1 peptides.
AB  - The majority of proteins targeted to the peroxisomal lumen contain a C-terminal
      peroxisomal targeting signal-1 (PTS1) that is bound by the peroxin Pex5p. The
      PTS1 is generally regarded as a C-terminal tripeptide that adheres to the
      consensus (S/A/C)(K/R/H)(L/M). Previously, we studied the binding affinity of
      peptides of the form YQX(-3)X(-2)X(-1) to the peptide-binding domain of human
      Pex5p (referred to as Pex5p-C). Optimal affinity was found for YQSKL, which bound
      with an affinity of 200 +/- 40 nM. To extend this work, we investigated the
      properties of a peptide containing the last 9 residues of acyl-CoA oxidase
      (RHYLKPLQSKL) and discovered that it binds to Pex5p-C with a dissociation
      constant of 1.4 +/- 0.4 nM, 180 times tighter than YQSKL. Further analysis
      revealed that the enhanced affinity is primarily due to the presence of leucine
      in the (-5) position. In addition, a peptide corresponding to the luciferase C
      terminus (YKGGKSKL) was found to bind Pex5p-C about 20 times tighter than YQSKL.
      The majority of this effect results from having lysine in position (-4). Catalase
      contains a noncanonical PTS1 (-AREKANL). The affinity of YQANL was found to be
      3600 +/- 400 nM. This relatively weak binding is consistent with previous
      unsuccessful attempts to direct chloramphenicol acetyltransferase to the
      peroxisome by fusing -ANL to its C-terminus (-GGA-ANL). The peptides YKANL,
      YEKANL, YREKANL, and YAREKANL all bound Pex5p-C with higher affinities than did
      YQANL, but the affinities are still lower than peptides that correspond to
      functional targeting signals in other contexts. Because both catalase and Pex5p
      are tetramers (as opposed to the monomeric Pex5p-C and the peptides used in our
      studies), multidentate effects on binding affinity between Pex5p and other
      oligomeric proteins should be considered. Our study provides direct thermodynamic
      data revealing that peptide binding to Pex5p-C binding is favored by lysine in
      the (-4) position and leucine in the (-5) position. Our results suggest that
      peptides or proteins with optimized residues in the (-4) and/or (-5) positions
      can bind to Pex5p with affinities that are at least two orders of magnitude
      greater than that of YQSKL, and that this stabilization can compensates for
      otherwise weakly binding PTS1s.

PMID- 15146485
TI  - Antibody recognition of chiral surfaces. Structural models of antibody complexes
      with leucine-leucine-tyrosine crystal surfaces.
AB  - Molecular models are built of the recognition domains of two antibodies, which
      are raised and selected against crystals of (L)leucine-(L)leucine-(L)tyrosine.
      The model of one antibody, which is stereo- and enantioselective, reveals
      astounding chemical and structural complementarity to the recognized crystal
      surface. The enantioselective binding of this antibody is explained by the
      significantly fewer chemical interactions arising in the complex, after docking
      of the antibody to the (D)Leu-(D)Leu-(D)Tyr crystal face, relative to its
      enantiomer, the (L)Leu-(L)Leu-(L)Tyr crystal face. The modeling and docking of
      the second antibody, which is poorly stereoselective and is not enantioselective,
      indicates that binding is based on electrostatic interactions. The docking models
      of the antibody-crystal complexes provide a rationale for the experimental
      results while demonstrating the power of modeling techniques to meet the
      challenge of describing antibody-antigen interactions in detail.

PMID- 15146486
TI  - Apolipoprotein E-low density lipoprotein receptor binding: study of protein
      protein interaction in rationally selected docked complexes.
AB  - Apolipoprotein E (apoE) is an important protein involved in lipid metabolism due
      to its interaction with members of the low-density lipoprotein receptor (LDLR)
      family. To further understand the molecular basis for this receptor-binding
      activity, an apoE fragment containing the receptor binding region (residues 135
      151) was docked onto the fifth LDLR ligand binding repeat (LR5) by computational
      methods. A subset of structures generated by the docking was rationally selected
      on the grounds of experimental data combined with modeling and was used for
      further analysis. The application and comparison of two different experimental
      structures for the apoE fragment underlines the local structural changes
      occurring in apoE when switching from a receptor-inactive to a receptor-active
      conformation. The body of interactions occurring at the interface between the two
      proteins is in very good agreement with the biochemical data available for both
      apoE and LDLR. Charged residues are involved in numerous ionic interactions and
      might therefore be important for the specificity of the interaction between apoE
      and LR5. In addition, the interface also features a tryptophan and a stacking of
      histidine residues, revealing that the association between the two proteins is
      not entirely governed by ionic interactions. In particular, the presence of
      histidine residues in the interface gives a structural basis for the pH-regulated
      release mechanism of apoE in the endosomes. The proposed molecular basis for apoE
      binding to LDLR could aid the design of strategies for targeting alterations in
      lipid transport and metabolism.

PMID- 15146487
TI  - Structure-based prediction of DNA-binding sites on proteins using the empirical
      preference of electrostatic potential and the shape of molecular surfaces.
AB  - Protein-DNA interactions play an essential role in the genetic activities of
      life. Many structures of protein-DNA complexes are already known, but the common
      rules on how and where proteins bind to DNA have not emerged. Many attempts have
      been made to predict protein-DNA interactions using structural information, but
      the success rate is still about 80%. We analyzed 63 protein-DNA complexes by
      focusing our attention on the shape of the molecular surface of the protein and
      DNA, along with the electrostatic potential on the surface, and constructed a new
      statistical evaluation function to make predictions of DNA interaction sites on
      protein molecular surfaces. The shape of the molecular surface was described by a
      combination of local and global average curvature, which are intended to describe
      the small convex and concave and the large-scale concave curvatures of the
      protein surface preferentially appearing at DNA-binding sites. Using these
      structural features, along with the electrostatic potential obtained by solving
      the Poisson-Boltzmann equation numerically, we have developed prediction schemes
      with 86% and 96% accuracy for DNA-binding and non-DNA-binding proteins,
      respectively.

PMID- 15146489
TI  - Protein-water interactions in ribonuclease A and angiogenin: a molecular dynamics
      study.
AB  - It is known that water molecules play an important role in the biological
      functioning of proteins. The members of the ribonuclease A (RNase A) family of
      proteins, which are sequentially and structurally similar, are known to carry out
      the obligatory function of cleaving RNA and individually perform other diverse
      biological functions. Our focus is on elucidating whether the sequence and
      structural similarity lead to common hydration patterns, what the common
      hydration sites are and what the differences are. Extensive molecular dynamics
      simulations followed by a detailed analysis of protein-water interactions have
      been carried out on two members of the ribonuclease A superfamily-RNase A and
      angiogenin. The water residence times are analyzed and their relationship with
      the characteristic properties of the protein polar atoms, such as their
      accessible surface area and mean hydration, is studied. The capacity of the polar
      atoms to form hydrogen bonds with water molecules and participate in protein
      water networks are investigated. The locations of such networks are identified
      for both proteins.

PMID- 15146488
TI  - Theoretical study of the ligand-CYP2B4 complexes: effect of structure on binding
      free energies and heme spin state.
AB  - The molecular origins of temperature-dependent ligand-binding affinities and
      ligand-induced heme spin state conversion have been investigated using free
      energy analysis and DFT calculations for substrates and inhibitors of cytochrome
      P450 2B4 (CYP2B4), employing models of CYP2B4 based on CYP2C5(3LVdH)/CYP2C9
      crystal structures, and the results compared with experiment. DFT calculations
      indicate that large heme-ligand interactions (ca. -15 kcal/mol) are required for
      inducing a high to low spin heme transition, which is correlated with large
      molecular electrostatic potentials (approximately -45 kcal/mol) at the ligand
      heteroatom. While type II ligands often contain oxygen and nitrogen heteroatoms
      that ligate heme iron, DFT results indicate that BP and MF heme complexes, with
      weak substrate-heme interactions (ca. -2 kcal/mol), and modest MEPS minima (>-35
      kcal/mol) are high spin. In contrast, heme complexes of the CYP2B4 inhibitor,
      4PI, the product of benzphetamine metabolism, DMBP, and water are low spin, have
      substantial heme-ligand interaction energies (<-15 kcal/mol) and deep MEPS minima
      (<-45 kcal/mol) near their heteroatoms. MMPBSA analysis of MD trajectories were
      made to estimate binding free energies of these ligands at the heme binding site
      of CYP2B4. In order to initially assess the realism of this approach, the binding
      free energy of 4PI inhibitor was computed and found to be a reasonable agreement
      with experiment: -7.7 kcal/mol [-7.2 kcal/mol (experiment)]. BP was determined to
      be a good substrate [-6.3 kcal/mol (with heme-ligand water), -7.3 kcal/mol
      (without ligand water)/-5.8 kcal/mol (experiment)], whereas the binding of MF was
      negligible, with only marginal binding binding free energy of -1.7 kcal/mol with
      2-MF bound [-3.8 kcal/mol (experiment)], both with and without retained heme
      ligand water. Analysis of the free energy components reveal that
      hydrophobic/nonpolar contributions account for approximately 90% of the total
      binding free energy of these substrates and are the source of their differential
      and temperature-dependent CYP2B4 binding. The results indicate the underlying
      origins of the experimentally observed differential binding affinities of BP and
      MF, and indicate the plausibility of the use of models derived from moderate
      sequence identity templates in conjunction with approximate free energy methods
      in the estimation of ligand-P450 binding affinities.

PMID- 15146490
TI  - Dynamics and energetics of water permeation through the aquaporin channel.
AB  - Structural properties of water inside bovine aquaporin-1 are investigated by
      molecular simulation. The calculations, which are based on the recently
      determined X-ray structure at 2.2 A resolution (Sui et al., Nature 2001;414:872
      878), are carried out on one monomeric subunit immersed in a water-n-octane-water
      bilayer. Molecular dynamics (MD) simulations suggest that His182, a fully
      conserved residue in the channel pore, is protonated in the delta position.
      Furthermore, they reveal a highly ordered water structure in the channel, induced
      by the electrostatic properties of the protein. Multiple-steering MD simulations
      are used to calculate the free-energy of water diffusion. To the best of our
      knowledge, this represents the first free-energy calculation based on the new,
      high-resolution structure of the pore. The calculated barrier is 2.5 kcal/mol,
      and it is associated to water permeation through the Asn-Pro-Ala (NPA) region of
      the pore, where water molecules are only hydrogen-bonded with themselves. These
      findings are fully consistent with those based on the previous MD studies on the
      human protein (de Groot and Grubmuller, Science 2001;294:2353-2357).

PMID- 15146491
TI  - Molecular dynamics simulations of structural changes during procaspase 3
      activation.
AB  - Molecular dynamics (MD) simulations of the structural rearrangements on the
      pathway leading to procaspase 3 activation are presented. A retrostructural
      approach is used to build procaspase 3 from mature caspase 3. The peptide bond
      that is cleaved during enzyme maturation is gradually reformed during the MD
      simulation and the most relevant structural changes that occur as a consequence
      are analyzed. The main structural features that characterize this procaspase 3
      model are compared with the available X-ray structure of procaspase 7 as the only
      zymogen structure that has been crystallised so far. The MD simulations indicate
      that in the free caspase 3, the flexible selectivity loop is already preorganized
      to accomodate the substrate. Such a preorganization is not present in either
      monomeric caspase 3 or in the procaspase 3 dimer, indicating that the structure
      of the selectivity loop is highly sensitive to perturbations.

PMID- 15146492
TI  - Molecular modeling of protein function regions.
AB  - Experimental protein structures often provide extensive insight into the mode and
      specificity of small molecule binding, and this information is useful for
      understanding protein function and for the design of drugs. We have performed an
      analysis of the reliability with which ligand-binding information can be deduced
      from computer model structures, as opposed to experimentally derived ones. Models
      produced as part of the CASP experiments are used. The accuracy of contacts
      between protein model atoms and experimentally determined ligand atom positions
      is the main criterion. Only comparative models are included (i.e., models based
      on a sequence relationship between the protein of interest and a known
      structure). We find that, as expected, contact errors increase with decreasing
      sequence identity used as a basis for modeling. Analysis of the causes of errors
      shows that sequence alignment errors between model and experimental template have
      the most deleterious effect. In general, good, but not perfect, insight into
      ligand binding can be obtained from models based on a sequence relationship,
      providing there are no alignment errors in the model. The results support a
      structural genomics strategy based on experimental sampling of structure space so
      that all protein domains can be modeled on the basis of 30% or higher sequence
      identity.

PMID- 15146493
TI  - Superfamily active site templates.
AB  - We show that three-dimensional signatures consisting of only a few functionally
      important residues can be diagnostic of membership in superfamilies of enzymes.
      Using the enolase superfamily as a model system, we demonstrate that such a
      signature, or template, can identify superfamily members in structural databases
      with high sensitivity and specificity. This is remarkable because superfamilies
      can be highly diverse, with members catalyzing many different overall reactions;
      the unifying principle can be a conserved partial reaction or chemical
      capability. Our definition of a superfamily thus hinges on the disposition of
      residues involved in a conserved function, rather than on fold similarity alone.
      A clear advantage of basing structure searches on such active site templates
      rather than on fold similarity is the specificity with which superfamilies with
      distinct functional characteristics can be identified within a large set of
      proteins with the same fold, such as the (beta/alpha)8 barrels. Preliminary
      results are presented for an additional group of enzymes with a different fold,
      the haloacid dehalogenase superfamily, suggesting that this approach may be
      generally useful for assigning reading frames of unknown function to specific
      superfamilies and thereby allowing inference of some of their functional
      properties.

PMID- 15146494
TI  - The emergence of catalytic and structural diversity within the beta-clip fold.
AB  - The beta-clip fold includes a diverse group of protein domains that are unified
      by the presence of two characteristic waist-like constrictions, which bound a
      central extended region. Members of this fold include enzymes like deoxyuridine
      triphosphatase and the SET methylase, carbohydrate-binding domains like the fish
      antifreeze proteins/Sialate synthase C-terminal domains, and functionally
      enigmatic accessory subunits of urease and molybdopterin biosynthesis protein
      MoeA. In this study, we reconstruct the evolutionary history of this fold using
      sensitive sequence and structure comparisons methods. Using sequence profile
      searches, we identified novel versions of the beta-clip fold in the bacterial
      flagellar chaperone FlgA and the related pilus protein CpaB, the StrU-like
      dehydrogenases, and the UxaA/GarD-like hexuronate dehydratases (SAF superfamily).
      We present evidence that these versions of the beta-clip domain, like the related
      type III anti-freeze proteins and C-terminal domains of sialic acid synthases,
      are involved in interactions with carbohydrates. We propose that the FlgA and
      CpaB-like proteins mediate the assembly of bacterial flagella and Flp pili by
      means of their interactions with the carbohydrate moieties of peptidoglycan. The
      N-terminal beta-clip domain of the hexuronate dehydratases appears to have
      evolved a novel metal-binding site, while their C-terminal domain is likely to
      adopt a metal-binding TIM barrel-like fold. Using structural comparisons, we show
      that the beta-clip fold can be further classified into two major groups, one that
      includes the SAF, SET, dUTPase superfamilies, and the other that includes the
      phage lambda head decoration protein, the beta subunit of urease and the C
      terminal domain of the molybdenum cofactor biosynthesis protein MoeA. Structural
      comparisons also suggest the beta-clip fold was assembled through the duplication
      of a three-stranded unit. Though the three-stranded units are likely to have had
      a common origin, we present evidence that complete beta-clip domains were
      assembled through such duplications, independently on multiple occasions. There
      is also evidence for circular permutation of the basic three-stranded unit on
      different occasions in the evolution of the beta-clip unit. We also describe how
      assembly of this fold from a basic three-stranded unit has been utilized to
      accommodate a variety of activities in its different versions.

PMID- 15146495
TI  - Relationships between amino acid sequence and backbone torsion angle preferences.
AB  - Statistical averages and correlations for backbone torsion angles of chymotrypsin
      inhibitor 2 are calculated by using the Rotational Isomeric States model of chain
      statistics. Statistical weights of torsional states of phipsi pairs, needed for
      the statistics of the full chain, are obtained in two different ways: 1) by using
      knowledge-based pairwise dependent phipsi energy maps from Protein Data Bank
      (PDB) and 2) by collecting torsion angle data from a large number of random coil
      configurations of an all-atom protein model with volume exclusion. Results
      obtained by using PDB data show strong correlations between adjacent torsion
      angle pairs belonging to both the same and different residues. These correlations
      favor the choice of the native-state torsion angles, and they are strongly
      context dependent, determined by the specific amino acid sequence of the protein.
      Excluded volume or steric clashes, only, do not introduce context-dependent
      phipsi correlations into the chain that would affect the choice of native-state
      torsional angles.

PMID- 15146496
TI  - A general clustering approach with application to the Miyazawa-Jernigan
      potentials for amino acids.
AB  - In this article, we address the problem of classification of amino acids.
      Starting from the Miyazawa-Jernigan matrix obtained from the relative positions
      of amino acids in the crystal structure of globular proteins, we develop a fully
      unsupervised method of classification for the amino acids. The method is based in
      the subdominant ultrametric associated to the distance induced by the Miyazawa
      Jernigan matrix and the maximum likelihood principle to determine the cluster
      structure. We obtain a classification consistent with the five groups used in the
      literature, although with some peculiarities. We also show the stability of our
      results against changes of the method used to classify the amino acids. Proteins
      2004.

PMID- 15146497
TI  - Single-body residue-level knowledge-based energy score combined with sequence
      profile and secondary structure information for fold recognition.
AB  - An elaborate knowledge-based energy function is designed for fold recognition. It
      is a residue-level single-body potential so that highly efficient dynamic
      programming method can be used for alignment optimization. It contains a backbone
      torsion term, a buried surface term, and a contact-energy term. The energy score
      combined with sequence profile and secondary structure information leads to an
      algorithm called SPARKS (Sequence, secondary structure Profiles and Residue-level
      Knowledge-based energy Score) for fold recognition. Compared with the popular PSI
      BLAST, SPARKS is 21% more accurate in sequence-sequence alignment in ProSup
      benchmark and 10%, 25%, and 20% more sensitive in detecting the family,
      superfamily, fold similarities in the Lindahl benchmark, respectively. Moreover,
      it is one of the best methods for sensitivity (the number of correctly recognized
      proteins), alignment accuracy (based on the MaxSub score), and specificity (the
      average number of correctly recognized proteins whose scores are higher than the
      first false positives) in LiveBench 7 among more than twenty servers of non
      consensus methods. The simple algorithm used in SPARKS has the potential for
      further improvement. This highly efficient method can be used for fold
      recognition on genomic scales. A web server is established for academic users on
      http://theory.med.buffalo.edu.

PMID- 15146498
TI  - A new perspective on analysis of helix-helix packing preferences in globular
      proteins.
AB  - For many years, statistical analysis of protein databanks has led to the belief
      that the steric compatibility of helix interfaces may be the source of observed
      preferences for particular angles between neighboring helices. Several elegant
      models describing how side chains on helices can interdigitate without steric
      clashes were able to account quite reasonably for the observed distributions.
      However, it was later recognized that the 'bare' measured angle distribution
      should be corrected to avoid statistical bias.12 Disappointingly, the rescaled
      distributions dramatically lost their similarity with theoretical predictions,
      casting doubts on the validity of the geometrical assumptions and models. In this
      article, we elucidate a few points concerning the proper choice of a random
      reference distribution. In particular we demonstrate the need for corrections
      induced by unavoidable uncertainties in determining whether two helices are in
      face-to-face contact or not and their relative orientations. By using this new
      rescaling, we show that 'true' packing angle preferences are well described by
      regular packing models, thus proving that preferential angles between contacting
      helices do exist.

PMID- 15146499
TI  - Importance of hydrophobic cluster formation through long-range contacts in the
      folding transition state of two-state proteins.
AB  - Understanding the folding pathways of proteins is a challenging task. The Phi
      value approach provides a detailed understanding of transition-state structures
      of folded proteins. In this work, we have computed the hydrophobicity associated
      with each residue in the folded state of 16 two-state proteins and compared the
      Phi values of each mutant residue. We found that most of the residues with high
      Phi value coincide with local maximum in surrounding hydrophobicity, or have
      nearby residues that show such maximum in hydrophobicity, indicating the
      importance of hydrophobic interactions in the transition state. We have tested
      our approach to different structural classes of proteins, such as alpha-helical,
      SH3 domains of all-beta proteins, beta-sandwich, and alpha/beta proteins, and we
      observed a good agreement with experimental results. Further, we have proposed a
      hydrophobic contact network pattern to relate the Phi values with long-range
      contacts, which will be helpful to understand the transition-state structures of
      folded proteins. The present approach could be used to identify potential
      hydrophobic clusters that may form through long-range contacts during the
      transition state.

PMID- 15146500
TI  - Prediction of the bonding states of cysteines using the support vector machines
      based on multiple feature vectors and cysteine state sequences.
AB  - The support vector machine (SVM) method is used to predict the bonding states of
      cysteines. Besides using local descriptors such as the local sequences, we
      include global information, such as amino acid compositions and the patterns of
      the states of cysteines (bonded or nonbonded), or cysteine state sequences, of
      the proteins. We found that SVM based on local sequences or global amino acid
      compositions yielded similar prediction accuracies for the data set comprising
      4136 cysteine-containing segments extracted from 969 nonhomologous proteins.
      However, the SVM method based on multiple feature vectors (combining local
      sequences and global amino acid compositions) significantly improves the
      prediction accuracy, from 80% to 86%. If coupled with cysteine state sequences,
      SVM based on multiple feature vectors yields 90% in overall prediction accuracy
      and a 0.77 Matthews correlation coefficient, around 10% and 22% higher than the
      corresponding values obtained by SVM based on local sequence information.

PMID- 15146502
TI  - Irreversible formation of intermediate BSA oligomers requires and induces
      conformational changes.
AB  - Understanding the relation between protein conformational changes and
      aggregation, and the physical mechanisms leading to such processes, is of primary
      importance, due to its direct relation to a vast class of severe pathologies.
      Growing evidence also suggests that oligomeric intermediates, which may occur
      early in the aggregation pathway, can be themselves pathogenic. The possible
      cytotoxicity of oligomers of non-disease-associated proteins adds generality to
      such suggestion and to the interest of studies of oligomer formation. Here we
      study the early stages of aggregation of Bovine Serum Albumin (BSA), a non
      pathogenic protein which has proved to be a useful model system. Dynamic light
      scattering and circular dichroism measurements in kinetic experiments following
      step-wise temperature rises, show that the "intermediate" form, which initiates
      large-scale aggregation, is the result of structural and conformational changes
      and concurrent formation of oligomers, of average size in the range of 100-200 A.
      Two distinct thresholds are observed. Beyond the first one oligomerization starts
      and causes partial irreversibility of conformational changes. Beyond the second
      threshold, additional secondary structural changes occurring in proteins being
      recruited progress on the same time scale of oligomerization. The concurrent
      behavior causes a mutual stabilization of oligomerization, and of structural and
      conformational changes, evidenced by a progressive increase of their
      irreversibility. This process interaction appears to be pivotal in producing
      irreversible oligomers.

PMID- 15146501
TI  - Modeling effects of mutations in coiled-coil structures: case study using
      epidermolysis bullosa simplex mutations in segment 1a of K5/K14 intermediate
      filaments.
AB  - The sequence of a protein chain determines both its conformation and its function
      in vivo. An attempt is made to gain an understanding of the classes of
      deformations that can arise in an important structural motif, the alpha-helical
      coiled coil, as a consequence of mutations occurring in its underlying heptad
      substructure. In order to do so we consider the model structure of segment 1A in
      intermediate filaments and then investigate the structures arising from each of
      the 22 mutations observed in cytokeratin K5/K14 molecules that lead to variants
      of epidermolysis bullosa simplex. These are refined separately using a molecular
      dynamics protocol. The mutations often result in a significant distortion of the
      backbone over a turn or so of the alpha helix in either the chain itself or its
      constituent partner, leading to the likelihood of impaired chain aggregation and
      hence molecular assembly. One mutant (K14-L143P; 1A-28) gave rise to structural
      distortion along almost the entire length of segment 1A. The remaining structures
      showed less deformation, and normal-looking intermediate filaments are likely in
      vivo. In addition, an identical mutation in the same position in each of the
      chains in the heterodimer did not necessarily give equivalent structural
      distortions. Although proline mutations frequently lead to the most severe
      structural deformations, a non-proline substitution (K14-R125S; 1A-10) gave rise
      to the largest local structural disruption that was observed. Unexpectedly,
      mutations in positions a and d were not always of the greatest structural
      significance, although three in position a were shown by AGADIR to result in a
      significant increase in alpha-helix stability.

PMID- 15146503
TI  - Role of protein in the primary step of the photoreaction of yellow protein.
AB  - We show the unexpectedly important role of the protein environment in the primary
      step of the photoreaction of the yellow protein after light illumination. The
      driving force of the trans-to-cis isomerization reaction was analyzed by a
      computational method. The force was separated into two different components: the
      term due to the protein-chromophore interaction and the intrinsic term of the
      chromophore itself. As a result, we found that the contribution from the
      interaction term was much greater than that coming from the intrinsic term. This
      accounts for the efficiency of the isomerization reaction in the protein
      environment in contrast to that in solution environments. We then analyzed the
      relaxation process of the chromophore on the excited-state energy surface and
      compared the process in the protein environment and that in a vacuum. Based on
      this analysis, we found that the bond-selectivity of the isomerization reaction
      also comes from the interaction between the chromophore and the protein
      environment.

PMID- 15146504
TI  - Direct measure of functional importance visualized atom-by-atom for photoactive
      yellow protein: application to photoisomerization reaction.
AB  - Photoreceptor proteins serve as efficient nano-machines for the photoenergy
      conversion and the photosignal transduction of living organisms. For instance,
      the photoactive yellow protein derived from a halophilic bacterium has the p
      coumaric acid chromophore, which undergoes an ultrafast photoisomerization
      reaction after light illumination. To understand the structure-function
      relationship at the atomic level, we used a computational method to find
      functionally important atoms for the photoisomerization reaction of the
      photoactive yellow protein. In the present study, a "direct" measure of the
      functional significance was quantitatively evaluated for each atom by calculating
      the partial atomic driving force for the photoisomerization reaction. As a
      result, we revealed the reaction mechanism in which the specific role of each
      functionally important atom has been well characterized in a systematic manner.
      In addition, we observed that this mechanism is strongly conserved during the
      thermal fluctuation of the photoactive yellow protein. We compared the
      experimental data of fluorescence decay constant of several different mutants and
      the present analysis. As a result, we found that the reaction rate constant is
      decreased when a large positive driving force is missing.

PMID- 15146506
TI  - A conserved hypothetical protein from Mycoplasma genitalium shows structural
      homology to nusb proteins.

PMID- 15146507
TI  - Crystal structure of isocitrate dehydrogenase from Aeropyrum pernix.

PMID- 15146510
TI  - Catalytic ionic hydrogenations.
AB  - Catalytic ionic hydrogenation of ketones occurs by proton transfer to a ketone
      from a cationic metal dihydride, followed by hydride transfer from a neutral
      metal hydride. This contrasts with traditional catalysts for ketone hydrogenation
      that require binding of the ketone to the metal and subsequent insertion of the
      ketone into a M-H bond. Ionic hydrogenation catalysts based on the inexpensive
      metals molybdenum and tungsten have been developed based on mechanistic
      understanding of the individual steps required in the catalytic reaction.

PMID- 15146505
TI  - Crystal structure of an Udp-n-acetylmuramate-alanine ligase MurC (TM0231) from
      Thermotoga maritima at 2.3 A resolution.

PMID- 15146512
TI  - Noncentrosymmetric organic solids with very strong harmonic generation response.
AB  - The molten reaction of 2-naphthol, 4-(aminomethyl)pyridine, and 4
      pyridinecarboxaldehyde at about 180 degrees C yields trans-2,3-dihydro-2,3-di(4'
      pyridyl)benzo[e]indole (1) which possesses two chiral centers, rather than an
      expected Betti-type reaction product with only one chiral carbon center. The same
      reactions, using 3-pyridinecarboxaldehyde, 4-cyanobenzaldehyde, or 3-
      cyanobenzaldehyde instead of 4-pyridinecarboxaldehyde produce the related
      compounds trans-2,3-dihydro-2-(4'-pyridyl)-3-(3"-pyridyl)benzo[e]indole (2),
      trans-2,3-dihydro-2-(4'-pyridyl)-3-(4"-cyanophenyl)benzo[e]indole (3), and trans
      2,3-dihydro-2-(4'-pyridyl)-3-(3"-cyanophenyl)benzo[e]indole (4), respectively.
      This reaction proceeds with a high degree of stereoselectivity with a trans/cis
      ratio of about 98:2 at elevated temperature. Compounds 1, 2, and 4 crystallize in
      a noncentrosymmetric space group (Pca2(1), Pca2(1), and Cc), while compound 3 has
      a chiral space group (P2(1)). These successfully acentric packing arrangements
      are probably due to the molecule bearing both two chiral centers and potential
      hydrogen-bonding groups. Furthermore, the reaction of racemic 6-hydroxy-2'-methyl
      2-naphthaleneacetic acid with ethyl-2-cyano-1-(4'-pyridyl)acrylic acetate in the
      presence of piperidine gives 1-pyridyl-2-ethoxycarbonyl-3-amino-1H-naphtho[2,1
      b]pyran-2'-methylacetic acid (5), which likewise crystallizes in a chiral space
      group. All of compounds are second harmonic generation (SHG) active, and have a
      very strong SHG response approximately about 8.0, 5.0, 12.0, 6.0, and 1.4 (for 1
      5 compounds) times that of urea. Ferroelectric property measurements indicate
      that compounds 1, 2, 4, and 5 may display ferroelectric behavior.

PMID- 15146513
TI  - Electronic and vibrational properties of fluorenone in the channels of zeolite L.
AB  - Fluorenone (C13H8O) was inserted into the channels of zeolite L by using gas
      phase adsorption. The size, structure, and stability of fluorenone are well
      suited for studying host-guest interactions. The Fourier transform IR, Raman,
      luminescence, and excitation spectra, in addition to thermal analysis data, of
      fluorenone in solution and fluorenone/zeolite L are reported. Normal coordinate
      analysis of fluorenone was performed, based on which IR and Raman bands were
      assigned, and an experimental force field was determined. The vibrational spectra
      can be used for nondestructive quantitative analysis by comparing a
      characteristic dye band with a zeolite band that has been chosen as the internal
      standard. Molecular orbital calculations were performed to gain a better
      understanding of the electronic structure of the system and to support the
      interpretation of the electronic absorption and luminescence spectra. Fluorenone
      shows unusual luminescence behavior in that it emits from two states. The
      relative intensity of these two bands depends strongly on the environment and
      changes unexpectedly in response to temperature. In fluorenone/zeolite L, the
      intensity of the 300 nm band (lifetime 9 micros) increases with decreasing
      temperature, while the opposite is true for the 400 nm band (lifetime 115
      micros). A model of the host-guest interaction is derived from the experimental
      results and calculations: the dye molecule sits close to the channel walls with
      the carbonyl group pointing to an Al3+ site of the zeolite framework. A secondary
      interaction was observed between the fluorenone's aromatic ring and the zeolite's
      charge-compensating cations.

PMID- 15146511
TI  - A versatile polypeptide platform for integrated recognition and reporting:
      affinity arrays for protein-ligand interaction analysis.
AB  - A molecular platform for protein detection and quantification is reported in
      which recognition has been integrated with direct monitoring of target-protein
      binding. The platform is based on a versatile 42-residue helix-loop-helix
      polypeptide that dimerizes to form four-helix bundles and allows site-selective
      modification with recognition and reporter elements on the side chains of
      individually addressable lysine residues. The well-characterized interaction
      between the model target-protein carbonic anhydrase and its inhibitor
      benzenesulfonamide was used for a proof-of-concept demonstration. An affinity
      array was designed where benzenesulfonamide derivatives with aliphatic or
      oligoglycine spacers and a fluorescent dansyl reporter group were introduced into
      the scaffold. The affinities of the array members for human carbonic anhydrase II
      (HCAII) were determined by titration with the target protein and were found to be
      highly affected by the properties of the spacers (dissociation constant Kd=0.02-3
      microM). The affinity of HCAII for acetazolamide (Kd=4 nM) was determined in a
      competition experiment with one of the benzenesulfonamide array members to
      address the possibility of screening substance libraries for new target-protein
      binders. Also, successful affinity discrimination between different carbonic
      anhydrase isozymes highlighted the possibility of performing future isoform
      expression profiling. Our platform is predicted to become a flexible tool for a
      variety of biosensor and protein-microarray applications within biochemistry,
      diagnostics and pharmaceutical chemistry.

PMID- 15146514
TI  - A general study of [(eta5-Cp')2Ti(eta2-Me3SiC2SiMe3)]-catalyzed hydroamination of
      terminal alkynes: regioselective formation of Markovnikov and anti-Markovnikov
      products and mechanistic explanation (Cp'=C5H5, C5H4Et, C5Me5).
AB  - A general study of the regioselective hydroamination of terminal alkynes in the
      presence of [(eta5-Cp)2Ti(eta2-Me3SiC2SiMe3)] (1), [(eta5-CpEt)2Ti(eta2
      Me3SiC2SiMe3)] (CpEt=ethylcyclopentadienyl) (2), and [(eta5-Cp*)2Ti(eta2
      Me3SiC2SiMe3)] (Cp*=pentamethylcyclopentadienyl) (3) is presented. While
      aliphatic amines give mainly the anti-Markovnikov products, anilines and aryl
      hydrazines yield the Markovnikov isomer as main products. Interestingly, using
      aliphatic amines such as n-butylamine and benzylamine the different catalysts
      lead to a significant change in the observed regioselectivity. Here, for the
      first time a highly selective switch from the Markovnikov to the anti-Markovnikov
      product is observed simply by changing the catalyst. Detailed theoretical
      calculations for the reaction of propyne with different substituted anilines and
      tert-butylamine in the presence of [(eta5-C5H5)Ti(=NR)(NHR)] (R=4-C6H4X; X=H, F,
      Cl, CH3, 2,6-dimethylphenyl) reveal that the experimentally observed
      regioselectivity is determined by the relative stability of the corresponding pi
      complexes 10. While electrostatic stabilization favors the Markovnikov
      performance for aniline, the steric repulsive destabilization disfavors the
      Markovnikov performance for tert-butylamine.

PMID- 15146515
TI  - Kinetic precipitation of solution-phase polyoxomolybdate followed by transmission
      electron microscopy: a window to solution-phase nanostructure.
AB  - This study aimed to elucidate the structural nature of the polydisperse,
      nanoscopic components in the solution and the solid states of partially reduced
      polyoxomolybdate derived from the [Mo132] keplerate, [(Mo)Mo5]12-[Mo2 acetate]30.
      Designer tripodal hexamine-tris-crown ethers and nanoscopic molybdate
      coprecipitated from aqueous solution. These microcrystalline solids distributed
      particle radii between 2-30 nm as assayed by transmission electron microscopy
      (TEM). The solid materials and their particle size distributions were snap shots
      of the solution phase. The mother liquor of the preparation of the [Mo132]
      keplerate after three days revealed large species (r=20-30 nm) in the
      coprecipitate, whereas [Mo132] keplerate redissolved in water revealed small
      species (3-7 nm) in the coprecipitate. Nanoparticles of coprecipitate were more
      stable than solids derived solely from partially reduced molybdate. The TEM
      features of all material analyzed lacked facets on the nanometer length scale;
      however, the structures diffracted electrons and appeared to be defect-free as
      evidenced by Moire patterns in the TEM images. Moire patterns and size-invariant
      optical densities of the features in the micrographs suggested that the molybdate
      nanoparticles were vesicular.

PMID- 15146516
TI  - Genuine heteroleptic complexes of early rare-earth metals: synthesis, X-ray
      structure, and their use for stereospecific isoprene polymerization catalysis.
AB  - Genuine heteroleptic neodymium and samarium complexes of formula [Cp*'Ln[(p
      tol)NN](BH4)] (Cp*' = C5Me4(nPr), (p-tol)NN = (p-tol)NC(Me)CHC(Me)N(p-tol), Ln =
      Sm: 1a, Ln = Nd: 1b) have been synthesized for the first time. These
      unprecedented homologues of early lanthanocenes are prepared by a metathetic
      reaction between their monocyclopentadienylbisborohydrido precursors with the
      corresponding potassium diketiminate. Both complexes were obtained in good yields
      and were characterized by 1H NMR spectroscopy and elemental analysis. Complex 1 a
      has an non-solvated dimeric structure, as indicated by its crystallographic data.
      The chloroneodymium analogue [Cp*'Nd[(p-tol)NN](Cl)] (2b) was only obtained as a
      part of a mixture. Analysis of crystals of 2b by X-ray diffraction revealed a
      molecular structure very similar to that of 1a. Preliminary isoprene
      polymerization experiments were carried out with 1 b in the presence of an
      alkylmagnesium coactivator. The resulting bimetallic Nd/Mg system behaves as an
      efficient and highly stereospecific catalyst with the synthesis of trans-1,4
      polyisoprene with more than 98% regularity. The control of the polymer structure
      is related to the steric hindrance around the lanthanide atom.

PMID- 15146517
TI  - Computational approaches to activity in rhodium-catalysed hydroformylation.
AB  - In this theoretical study on rhodium-catalysed hydroformylation we examine an
      unmodified hydridorhodium(I) carbonyl system a together with three variants
      modified by the model phosphane ligands PF3 (system b), PH3 (system c) and PMe3
      (system d), which show increasing basicity on the Tolman chi parameter scale. The
      olefinic substrate for all systems is ethene. Based on the dissociative
      hydroformylation mechanism, static and dynamic quantum-mechanical approaches are
      made for preequilibria and the whole catalytic cycle. Agreement with experimental
      results was achieved with regard to the predominance of phosphane
      monocoordination in systems b-d, different sensitivity of unmodified and modified
      systems towards hydrogen pressure and the early location of the rate-determining
      step. Neither the catalytic cycle as a whole nor olefin insertion as an important
      selectivity-determining step gives a clear picture of activity differences among
      a-d. However, the crucial first catalytic step, association of ethene to the
      active species [HRhL3] (L=CO, PR3), may play the key role in the experimentally
      observed higher activity of a and systems with less basic phosphane ligands
      modelled by b.

PMID- 15146519
TI  - Tris(oxalato)phosphorus acid and its lithium salt.
AB  - The conversion of three equivalents of anhydrous oxalic acid with phosphorus
      pentachloride yields tris(oxalato)phosphorus acid 1, which crystallizes from
      diethyl ether solutions as protonated diethyl ether complex
      [(Et2O)2H](+)[P(C2O3)3)]-. The superacidic compound can be used as catalyst for
      Friedel-Crafts-type reactions. Upon neutralization with lithium hydride, the
      lithium salt Li[P(C2O3)3] 2 is obtained, which is highly soluble in aprotic
      solvents and which exhibits a wide voltage window. Thus, the lithium compound is
      a promising candidate as electrolyte for high performance non-aqueous batteries.

PMID- 15146518
TI  - Synthesis of (E)-alpha-hydroxy-beta,gamma-unsaturated amides with high
      selectivity from alpha,beta-epoxyamides by using catalytic samarium diiodide or
      triiodide.
AB  - The highly stereoselective synthesis of (E)-alpha-hydroxy-beta,gamma-unsaturated
      amides starting from alpha,beta-epoxyamides, by using catalytic SmI2 or SmI3, was
      achieved. This transformation can also be carried out by using SmI2 generated in
      situ from samarium powder and diiodomethane. The starting compounds 1 are easily
      prepared by the reaction of enolates derived from alpha-chloroamides with ketones
      at -78 degrees C. A mechanism to explain this transformation has been proposed.
      Cyclopropanation of (E)-alpha-hydroxy-beta,gamma-unsaturated amides has been
      performed to demonstrate their synthetic applications.

PMID- 15146520
TI  - Hydrogenation studies involving halobis(phosphine)-rhodium(I) dimers: use of
      parahydrogen induced polarisation to detect species present at low concentration.
AB  - Reaction of [RhCl(PPh3)2]2 with parahydrogen revealed that the binuclear
      dihydride [Rh(H)2(PPh3)2mu-Cl)2Rh(PPh3)2] and the tetrahydride complex
      [Rh(H)2(PPh3)2(mu-Cl)]2 are readily formed. While magnetisation transfer from
      free H2 into both the hydride resonances of the tetrahydride and
      [Rh(H)2Cl(PPh3)3] is observable, neither transfer into [Rh(H)2(PPh3)2(mu
      Cl)2Rh(PPh3)2] nor transfer between the two binuclear complexes is seen.
      Consequently [Rh(H)2(PPh3)2(mu-Cl)]2 and [Rh(H)2(PPh3)2(mu-Cl)2Rh(PPh3)2] are not
      connected on the NMR timescale by simple elimination or addition of H2. The rapid
      exchange of free H2 into the tetrahydride proceeds via reversible halide bridge
      rupture and the formation of [Rh(H)2(PPh3)2(mu-Cl)RhCl(H)2(PPh3)2]. When these
      reactions are examined in CD2Cl2, the formation of the solvent complex
      [Rh(H)2(PPh3)2(mu-Cl)2Rh(CD2Cl2)(PPh3)] and the deactivation products
      [Rh(Cl)(H)PPh3)2(mu-Cl)(mu-H)Rh(Cl)(H)PPh3)2] and [Rh(Cl)(H)(CD2Cl2)(PPh3)(mu
      Cl)(mu-H)Rh(Cl)(H)PPh3)2] is indicated. In the presence of an alkene and
      parahydrogen, signals corresponding to binuclear complexes of the type
      [Rh(H)2(PPh3)2(mu-Cl)(2)(Rh)(PPh3)(alkene)] are detected. These complexes undergo
      intramolecular hydride interchange in a process that is independent of the
      concentration of styrene and catalyst and involves halide bridge rupture,
      followed by rotation about the remaining Rh-Cl bridge, and bridge re
      establishment. This process is facilitated by electron rich alkenes.
      Magnetisation transfer from the hydride ligands of these complexes into the alkyl
      group of the hydrogenation product is also observed. Hydrogenation is proposed to
      proceed via binuclear complex fragmentation and trapping of the resultant
      intermediate [RhCl(H)2PPh3)2] by the alkene. Studies on a number of other
      binuclear dihydride complexes including [(H)(Cl)Rh(PMe3)2(mu-H)(mu
      Cl)Rh(CO)(PMe3)], [(H)2Rh(PMe3)2(mu-Cl)2Rh(CO)(PMe3)] and [HRh(PMe3)2(mu-H)(mu
      Cl)2Rh(CO)(PMe3)] reveal that such species are able to play a similar role in
      hydrogenation catalysis. When the analogous iodide complexes [RhIPPh3)2]2 and
      [RhI(PPh3)3] are examined, [Rh(H)2(PPh3)2(mu-I)2Rh(PPh3)2], [Rh(H)2(PPh3)2(mu
      I)]2 and [Rh(H)2I(PPh3)3] are observed in addition to the corresponding binuclear
      alkene-dihydride products. The higher initial activity of these precursors is
      offset by the formation of the trirhodium phosphide bridged deactivation product,
      [[(H)(PPh3)Rh(mu-H)(mu-I)(mu-PPh2)Rh(H)(PPh3)](mu-I)2Rh(H)2PPh3)2]

PMID- 15146521
TI  - Road maps for nitrogen-transfer catalysis: the challenge of the osmium(VIII)
      catalyzed diamination.
AB  - Although the Sharpless dihydroxylation has been used on laboratory and industrial
      scales for several decades, an analogous osmium-catalyzed diamination is unknown.
      To explore the reaction of osmium(VIII) oxo-imido complexes with C=C bonds,
      density functional calculations have been performed. The calculations predict a
      chemoselective and perispecific [3+2] addition of the NH=Os=NH moiety of
      diimidodioxoosmium(VIII) to ethylene, yielding dioxoosma-2,5-diazolidine. At
      first sight, this metallacycle seems extremely stable; it is more stable than
      diimidoosma-2,5-dioxolane by 40 kcal mol(-1). However, a comparison of the
      thermodynamic reaction profiles for catalytic model cycles of dihydroxylation,
      aminohydroxylation, and diamination reveals that, contrary to common belief, the
      instability of the metal=N bond in the osmium(VIII) imido complex rather than the
      stability of the metal-N bond in the osmium(VI) intermediate causes most of the
      energy difference between the metallacycles. Substituents on the substrate have a
      small effect on the thermodynamic reaction profiles, whereas substituents on the
      imido ligands allow steric and electronic control of the reaction free enthalpies
      in the range of up to 25 kcal mol(-1). The results of this study help identify
      potential challenges in the development of the as-yet hypothetical title reaction
      and provide a modular concept for exploring novel catalytic routes.

PMID- 15146522
TI  - A catalytic antibody against a tocopherol cyclase inhibitor.
AB  - The cyclic ammonium cation 5 and its guanidinium analogue 4 are inhibitors of
      tocopherol cyclase. Monoclonal antibodies were raised against protein conjugates
      of the haptens 1-3 and screened for catalytic reactions with alkene 8, a short
      chain analogue of the natural substrate phytyl-hydroquinone 6, and its enol ether
      analogues 10a,b. Antibody 16E7 raised against hapten 3 was found to catalyze the
      hydrolysis of Z enol ether 10a to form hemiacetal 12 with an apparent rate
      acceleration of k(cat)/k(uncat)=1400. Antibody 16E7 also catalyzed the
      elimination of Kemp's benzisoxazole 59. The absence of cyclization in the
      reaction of enol ether 10a was attributed to the competition of water molecules
      for the oxocarbonium cation intermediate within the antibody binding pocket.
      Hapten and reaction design features contributing to this outcome are discussed.
      Antibody 16E7 provides the first example of a carboxyl group acting both as an
      acid in an intrinsically acid-catalyzed process and as a base in an intrinsically
      base-catalyzed process, as expected from first principles. In contrast to the
      many examples of general-acid-catalyzed processes known to be catalyzed by
      catalytic antibodies, the specific-acid-catalyzed cyclization of phytyl
      hydroquinone 6 or its analogue 8 still eludes antibody catalysis.

PMID- 15146523
TI  - Indium-mediated regio- and diastereoselective reduction of norbornyl alpha
      diketones.
AB  - A novel, efficient, and regio- as well as diastereoselective conversion of non
      enolizable bicyclic alpha-diketones into synthetically useful acyloins mediated
      by indium metal is described. The reduction is highly diastereoselective, leading
      exclusively to endo-acyloins (endo-hydroxyl groups) in excellent yields, and
      tolerates a variety of sensitive substituents, such as acetate, ester, and
      bridgehead halogens. The regioselectivity in the reductions of monosubstituted
      alpha-diketones varied from 70:30 to 100:0 for the two possible isomeric
      alcohols. The methodology is extended to the synthesis of highly functionalized
      cyclopentane carboxaldehydes, potential building blocks in organic syntheses, by
      cleavage of the acyloins by treating them with Pb(OAc)4 in MeOH/PhH. Allylindium
      additions to carboxaldehydes 22 have been found to be highly diastereoselective.

PMID- 15146524
TI  - Molecular logic gates based on pentacyanoferrate complexes: from simple gates to
      three-dimensional logic systems.
AB  - The article presents new aspects of reactivity of two pentacyanoferrates:
      [Fe(CN)5NO]2- and [Fe(CN)5N(O)SR]3-. The dependence of thermodynamic functions on
      cations was found for the reaction between nitroprusside and thiolate. The
      thermodynamic data are interpreted in terms of ion pairing and changes in the
      solvation shell of the cations. It was found that the reaction enthalpies and
      entropies depend strongly on the cation radius. The reaction volume in turn is
      strongly affected by the structure and properties of the hydration shell. Careful
      data analysis allowed the contribution of partial cation dehydration to the total
      reaction volume to be determined. The experimental results were also interpreted
      in terms of chemical logic gates. Complex logic systems were built from a number
      of cells containing a switching compound arranged in different geometric
      patterns. Increasing the dimensionality of these arrangements leads to really
      complex logic systems containing up to 20 AND and OR logic gates. The system is
      capable of processing up to 16 bits of input data.

PMID- 15146525
TI  - Multi-step application of immobilized reagents and scavengers: a total synthesis
      of epothilone C.
AB  - The total synthesis of the cytotoxic antitumour natural product epothilone C has
      provided a stage for the exploitation and further development of immobilized
      reagent methods. A stereoselective convergent synthetic strategy was applied,
      incorporating polymer-supported reagents, catalysts, scavengers and catch-and
      release techniques to avoid frequent aqueous work-up and chromatographic
      purification.

PMID- 15146526
TI  - Crystallization-induced asymmetric transformation of chiral-at-metal
      ruthenium(II) complexes bearing achiral ligands.
AB  - Recently, we observed that the enantiopure Lambda form of the tributylammonium
      salt of the chiral anion tris[tetrachlorobenzene-1,2-bis(olato)]phosphate, also
      named Trisphat, was able to induce an efficient resolution of a Delta,Lambda
      racemic mixture of cis-[Ru(dmp)2(NCCH3)2](PF6)2 (dmp=2,9-dimethyl-1,10
      phenanthroline) due to the spontaneous and selective precipitation of the
      heterochiral pair [Delta-Ru(dmp)2(CH3CN)2][Lambda-Trisphat]2. We report here that
      the combination of such a stereoselective precipitation process and irradiation
      results in the quantitative conversion of the initial [Ru(dmp)2(NCCH3)2]2+
      racemate into only one of the two enantiomers. This is the first example in
      inorganic chemistry of an asymmetric transformation that leads to a chiral
      complex with no chiral ligand. Finally, three new racemic ruthenium bis(diimine)
      complexes, namely [Ru(dmp)2(NCCH3)Py](PF6)2 (Py=pyridine), [Ru(dmp)2(1,3
      diaminopropane)](PF6)2, and [Ru(dmp)2(ethylenediamine)](PF6)2 were synthesized.
      For all of them, crystallization-induced asymmetric transformation proved to be
      an efficient way of obtaining the corresponding optically active chiral-at-metal
      complexes in high yields and with excellent stereoselectivities.

PMID- 15146527
TI  - Molecular shuttles based on tetrathiafulvalene units and 1,5-dioxynaphthalene
      ring systems.
AB  - Six different degenerate [2]rotaxanes were synthesized and characterized. The
      rotaxanes contained either two tetrathiafulvalene (TTF) units or two 1,5
      dioxynaphthalene (DNP) ring systems, both of which serve as recognition sites for
      a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring. Three different spacer units
      were incorporated into the dumbbell components of the [2]rotaxanes between the
      recognition sites. They include a polyether chain, a terphenyl unit, and a
      diphenyl ether linker, all of which were investigated in order to probe the
      effect of the spacers on the rate of the shuttling process. Data from dynamic 1H
      NMR spectroscopy revealed a relatively small difference in the DeltaG++ values
      for the shuttling process in the [2]rotaxanes containing the three different
      spacers, in contrast to a large difference between the TTF-containing rotaxanes
      (18 kcal mol(-1)) and the DNP-containing rotaxanes (15 kcal mol(-1)). This 3 kcal
      mol(-1) difference is predominantly a result of a ground-state effect, reflecting
      the much stronger binding of TTF units to the CBPQT4+ ring in comparison with DNP
      ring systems. An examination of the enthalpic (DeltaH++) and entropic (DeltaS++)
      components for the shuttling process in the DNP-containing rotaxanes revealed
      significant differences between the three spacers, a property which could be
      important in designing new molecules for incorporation into molecular electronic
      and nanoelectromechanical (NEMs) devices.

PMID- 15146528
TI  - The advantage of being virtual--target-induced adaptation and selection in
      dynamic combinatorial libraries.
AB  - Numerical simulations are presented that describe the adaptive behavior of simple
      dynamic combinatorial libraries (DCLs) upon addition of a target. By studying the
      effect of various parameters such as the network topology, the initial
      concentrations, the association constants, and the binding affinities, general
      characteristics of such systems were derived. It is shown that the adaptation may
      lead to the amplification of molecules with a high affinity to the target, but
      only for specific boundary conditions. Furthermore, it is demonstrated that the
      selection process can be refined by using an evolutionary approach. These results
      are of importance for the design of selection experiments with DCLs.

PMID- 15146529
TI  - Solvent effects on 195Pt and 205Tl NMR chemical shifts of the complexes [(NC)5Pt-
      Tl(CN)n]n- (n=0-3), and [(NC)5Pt--Tl--Pt(CN)5]3- studied by relativistic density
      functional theory.
AB  - The 295Pt and 205Tl NMR chemical shifts of the complexes [(NC)5Pt-Tl(CN)n]n- n=0
      3, and of the related system [(NC)5Pt--Tl--Pt(CN)5]3- have been computationally
      investigated. It is demonstrated that based on relativistically optimized
      geometries, by applying an explicit first solvation shell, an additional implicit
      solvation model to represent the bulk solvent effects (COSMO model), and a DFT
      exchange-correlation potential that was specifically designed for the treatment
      of response properties, that the experimentally observed metal chemical shifts
      can be calculated with satisfactory accuracy. The metal chemical shifts have been
      computed by means of a two-component relativistic density functional approach.
      The effects of electronic spin-orbit coupling were included in all NMR
      computations. The impact of the choice of the reference, which ideally should not
      affect the accuracy of the computed chemical shifts, is also demonstrated.
      Together with recent calculations by us of the Pt and Tl spin-spin coupling
      constants, all measured metal NMR parameters of these complexes are now
      computationally determined with sufficient accuracy in order to allow a detailed
      analysis of the experimental results. In particular, we show that interaction of
      the complexes with the solvent (water) must be an integral part of such an
      analysis.

PMID- 15146530
TI  - Syntheses and reactions of hexavalent organotellurium compounds bearing five or
      six tellurium-carbon bonds.
AB  - A variety of hexaorganotellurium compounds, Ar(6-n)(CH3)nTe [Ar=4-CF3C6H4, n=0
      (1a), n=1 (3a), n=2 (trans-4a and cis-4a), n=3 (mer-5a), n=4 (trans-6a); Ph, n=0
      (1b), n=1 (3b), n=2 (trans-4b); 4-CH3C6H4, n=0 (1c), n=1 (3c), n=2 (trans-4c),
      n=4 (trans-6c); 4-BrC6H4, n=0 (1d)] and Ar5(R)Te [Ar=4-CF3C6H4, R=4-CH3OC6H4 (8);
      Ar=4-CF3C6H4, R=vinyl (9), Ar=Ph, R=vinyl (10), Ar=4-CF3C6H4, R=PhSCH2 (11),
      Ar=Ph, R=PhSCH2 (12), Ar=4-CF3C6H4, R=nBu (13)] and pentaorganotellurium halides,
      Ar5TeX [Ar=4-CF3C6H4, X=Cl (2a-Cl), X=Br (2a-Br); Ar=Ph, X=Cl (2b-Cl), X=Br (2b
      Br); Ar=4-CH3C6H4, X=Cl (2c-Cl), X=Br (2c-Br); Ar=4-BrC6H4, X=Br (2d-Br)] and (4
      CF3C6H4)4(CH3)TeX [X=Cl (trans-7a-Cl) and X=Br (trans-7a-Br)] were synthesized by
      the following methods: 1) one-pot synthesis of 1 a, 2) the reaction of SO2Cl2 or
      Br2 with Ar5Te(-)Li+ generated from TeCl4 or TeBr4 with five equivalents of ArLi,
      3) reductive cleavage of Ar(6-m)(CH3)(m)Te (m=0 or 2) with KC8 followed by
      treatment with CH3I, 4) valence expansion reaction from low-valent tellurium
      compounds by treatment with KC8 followed by reaction with CH3I, 5) nucleophilic
      substitution of Ar(6-y-z)(CH3)zTeX(y-z) (X=Cl, Br, OTf; z=0, 1; y=1, 2) with
      organolithium reagents. The scope and limitations and some details for each
      method are discussed and electrophilic halogenation of the hexaorganotellurium
      compounds is also described.

PMID- 15146531
TI  - Synthesis of C3 benzo[1,2-e:3,4-e':5,6-e"]tribenzo[l]acephenanthrylenes ("crushed
      fullerene" derivatives) by intramolecular palladium-catalyzed arylation.
AB  - The C60 polyarenes 4, 5, 18 a, and 18 b have been synthesized from truxene by
      triple alkylation at C5, C10, and C15 followed by a palladium-catalyzed
      intramolecular arylation. The synthesis of "crushed fullerene" C60H30 (2) is the
      most efficient reported to date and proceeds in 33% overall yield.

PMID- 15146533
TI  - Forisomes, a novel type of Ca(2+)-dependent contractile protein motor.

PMID- 15146534
TI  - Early molecular events in the assembly of the focal adhesion-stress fiber complex
      during fibroblast spreading.
AB  - Cell adhesion to the extracellular matrix triggers the formation of integrin
      mediated contact and reorganization of the actin cytoskeleton. Examination of
      nascent adhesions, formed during early stages of fibroblast spreading, reveals a
      variety of forms of actin-associated matrix adhesions. These include: (1). small
      ( approximately 1 microm), dot-like, integrin-, vinculin-, paxillin-, and
      phosphotyrosine-rich structures, with an F-actin core, broadly distributed over
      the ventral surfaces of the cells; (2). integrin-, vinculin-, and paxillin
      containing "doublets" interconnected by short actin bundles; (3). arrays of actin
      vinculin complexes. Such structures were formed by freshly plated cells, as well
      as by cells recovering from latrunculin treatment. Time-lapse video microscopy of
      such cells, expressing GFP-actin, indicated that long actin cables are formed by
      an end-to-end lining-up and apparent fusion of short actin bundles. All these
      structures were prominent during cell spreading, and persisted for up to 30-60
      min after plating. Upon longer incubation, they were gradually replaced by stress
      fibers, associated with focal adhesions at the cell periphery. Direct examination
      of paxillin and actin reorganization in live cells revealed alignment of paxillin
      doublets, forming long and highly dynamic actin bundles, undergoing
      translocation, shortening, splitting, and convergence. The mechanisms underlying
      the assembly and reorganization of actin-associated focal adhesions and the
      involvement of mechanical forces in regulating their dynamic properties are
      discussed.

PMID- 15146535
TI  - Glutamylated and glycylated tubulin isoforms in the aberrant sperm axoneme of the
      gall-midge fly, Asphondylia ruebsaameni.
AB  - The axonemal organization expressed in the sperm flagella of the cecidomyiid
      dipteran Asphondylia ruebsaameni is unconventional, being characterized by the
      presence of an exceedingly high number of microtubular doublets and by the
      absence of both the inner dynein arms and the central pair/radial spoke complex.
      Consequently, its motility, both in vivo and in vitro, is also peculiar. Using
      monoclonal antibodies directed against posttranslational modifications, we have
      analyzed the presence and distribution of glutamylated and glycylated tubulin
      isoforms in this aberrant axonemal structure, and compared them with those of a
      reference insect species (Apis mellifera), endowed with a conventional axoneme.
      Our results have shown that the unorthodox structure and motility of the
      Asphondylia axoneme are concomitant with: (1). a very low glutamylation extent in
      the alpha-tubulin subunit, (2). a high level of glutamylation in the beta
      subunit, (3). an extremely low total extent of glycylation, with regard to both
      monoglycylated and polyglycylated sites, either in alpha- or in beta-tubulin,
      (4). the presence of a strong labeling of glutamylated tubulin isoforms at the
      proximal end of the axoneme, and (5). a uniform distribution of glutamylated as
      well as glycylated isoforms along the rest of the axoneme. Thus, our data
      indicate that tubulin molecular heterogeneity is much lower in the Asphondylia
      axoneme than in the conventional 9+2 axoneme with regard to both isoform content
      and isoform distribution along the axoneme.

PMID- 15146536
TI  - Molecular dissection of the fibroblast-traction machinery.
AB  - Motile fibroblasts generate forces that can be expressed as cell migration or as
      traction, the drawing-in of extracellular matrix. Traction by cultured
      fibroblasts can induce a rapid concerted reorganization of collagen gel, creating
      a pattern of collagen alignment similar to that seen in tendons and ligaments. In
      such fibrous connective tissues, after pattern morphogenesis is complete, ongoing
      traction may be responsible for the maintenance of proper form and function. The
      molecules that generate and transmit forces have been catalogued; however, how
      these nanometer-scale molecules contribute to millimeter-scale patterns has not
      been directly tested. Here, we placed pairs of explants of human periodontal
      ligament fibroblasts in collagen gels, where ligament-like straps of anisotropic
      collagen formed on the axes between them. We scrutinized the traction apparatus
      using electron microscopy, video microscopy, and computer-based pattern analysis,
      augmented with pharmacologic inhibitors of cytoskeletal function. Patterning was
      marked by the co-alignment of collagen, fibroblasts, and their actin
      cytoskeletons, all parallel to the axis between explants. The pattern was
      diminished by depolymerizing actin filaments or by blocking myosin activity, but
      was accentuated by depolymerizing microtubules. The plasma membrane also seems to
      contribute to the traction force. These molecular components combine to exert a
      sub-maximal traction force on the matrix, suggesting that the force may be
      regulated to ensure tissue tensional homeostasis.

PMID- 15146537
TI  - Rac-induced increase of phosphorylation of myosin regulatory light chain in HeLa
      cells.
AB  - The pathways by which activation of the small GTP-binding protein Rac causes
      cytoskeletal changes are not fully understood but are likely to involve both
      assembly of new actin filaments and reorganization of actin filaments driven by
      the actin-dependent ATPase activity of myosin II. Here we show that expression of
      active RacQ61 in growing HeLa cells, in addition to inducing ruffling,
      substantially enhances the level of phosphorylation of serine-19 of the myosin II
      regulatory light chain (MLC), which would increase actomyosin II ATPase and motor
      activities. Phosphorylated myosin was localized to RacQ61-induced ruffles and
      stress fibers. RacQ61-induced phosphorylation of MLC was reduced by a maximum of
      about 38% by an inhibitor (Tat-PAK) of p21-activated kinase (PAK), about 35% by
      an inhibitor (Y-27632) of Rho kinase, 51% by Tat-PAK plus Y-27632, and 10% by an
      inhibitor (ML7) of myosin light chain kinase. Staurosporine, a non-specific
      inhibitor of serine/threonine kinases, reduced RacQ61-induced phosphorylation of
      MLC by about 58%, at the maximum concentration that did not kill cells. Since Rac
      activates PAK and PAK can phosphorylate MLC, these data strongly suggest that PAK
      is responsible for a significant fraction of RacQ61-induced MLC phosphorylation.
      To our knowledge, this is the first evidence that active Rac causes
      phosphorylation of MLC in cells, thus implicating activation of the ATPase
      activity of actomyosin II as one of the ways by which Rac may induce cytoskeletal
      changes.

PMID- 15146538
TI  - C2C12 co-culture on a fibroblast substratum enables sustained survival of
      contractile, highly differentiated myotubes with peripheral nuclei and adult fast
      myosin expression.
AB  - We describe a simple culture method for obtaining highly differentiated clonal
      C2C12 myotubes using a feeder layer of confluent fibroblasts, and document the
      expression of contractile protein expression and aspects of myofibre morphology
      using this system. Traditional culture methods using collagen- or laminin-coated
      tissue-culture plastic typically results in a cyclic pattern of detachment and
      reformation of myotubes, rarely producing myotubes of a mature adult phenotype.
      C2C12 co-culture on a fibroblast substratum facilitates the sustained culture of
      contractile myotubes, resulting in a mature sarcomeric register with evidence for
      peripherally migrating nuclei. Immunoblot analysis demonstrates that desmin,
      tropomyosin, sarcomeric actin, alpha-actinin-2 and slow myosin are detected
      throughout myogenic differentiation, whereas adult fast myosin heavy chain
      isoforms, members of the dystrophin-associated complex, and alpha-actinin-3 are
      not expressed at significant levels until >6 days of differentiation, coincident
      with the onset of contractile activity. Electrical stimulation of mature myotubes
      reveals typical and reproducible calcium transients, demonstrating functional
      maturation with respect to calcium handling proteins. Immunocytochemical staining
      demonstrates a well-defined sarcomeric register throughout the majority of
      myotubes (70-80%) and a striated staining pattern is observed for desmin,
      indicating alignment of the intermediate filament network with the sarcomeric
      register. We report that culture volume affects the fusion index and rate of
      sarcomeric development in developing myotubes and propose that a fibroblast
      feeder layer provides an elastic substratum to support contractile activity and
      likely secretes growth factors and extracellular matrix proteins that assist
      myotube development.

PMID- 15146540
TI  - Purification and characterization of arginine kinase from the American cockroach
      (Periplaneta americana).
AB  - The isolation and characterization of homogeneous arginine kinase from the
      cockroach is reported. The purification protocol produces 6.6 mg of pure enzyme
      from 6.8 g of whole cockroach. The purified enzyme cross-reacts with a
      heterologous antibody and monoclonal antibody against arginine kinase from the
      shrimp. Both antibody preparations also cross-react with extracts from several
      species known to contain monomeric arginine kinase, but fail to react with
      extracts from organisms containing dimeric arginine kinase. Cockroach arginine
      kinase has a molecular mass of approximately 43,000 determined from measurements
      by gel filtration and gel electrophoresis. Compared with other arginine kinases,
      the enzyme from the cockroach is relatively thermostable (50% activity retained
      at 50 degrees C for 10 min) and has a pH optima of 8.5 and 6.5-7.5, for the
      forward and reverse reactions, respectively. Treatment with 5,5'dithiobis[2
      nitrobenzoic acid] indicates that arginine kinase has a single reactive
      sulfhydryl group and, interestingly, the reaction is biphasic. The Michaelis
      constants for the phosphagen substrates, arginine: 0.49 mM, phosphoarginine: 0.94
      mM, and nucleotide substrates MgATP: 0.14 mM, MgADP: 0.09 mM, are in the range
      reported for other arginine kinases. A 1% solution of pure enzyme has an
      absorbance of 7.0 at 280 nm. Calculations based on circular dichroic spectra
      indicate that arginine kinase from the cockroach has 12% alpha-helical structure.
      The intrinsic protein fluorescence emission maximum at 340 nm suggests that
      tryptophan residues are below the surface of the protein and not exposed to
      solvent. Arginine kinase from the cockroach and shrimp are known to be
      deleterious immunogens towards humans. The availability of pure protein, its
      characterization and potential regulation of activity, will be useful in
      developing agents to control the cockroach population and its destructive role in
      agriculture and human health.

PMID- 15146542
TI  - Fatty acid and sex pheromone changes and the role of glandular lipids in the Z
      strain of the European corn borer, Ostrinia nubilalis (Hubner).
AB  - Lipids in the sex pheromone gland of females of the Z-strain of Ostrinia
      nubilalis were analyzed for fatty acyl pheromone analogs (FAPAs) and other
      potential biosynthetic intermediates. More than 80% of the FAPAs were found in
      the triacylglycerols (TGs), with smaller amounts found in the phosphatidyl
      cholines, ethanolamines, and serines. Analysis of the TGs by lipase revealed that
      the two FAPAs were distributed fairly evenly among all three stereospecific
      positions. Comparison of changes in titers of key glandular fatty acids with
      those of pheromone components, with respect to photoperiodic time and age of
      females, showed that both FAPA and pheromone titers exhibited a cyclical pattern
      with peaks in the scotophase and valleys in the photophase. However, whereas
      pheromone titer tended to peak in the first half of the scotophase, FAPA titer
      peaked at the end of the scotophase. Significantly, the titer of the FAPA of the
      minor component, (E)-11-tetradecenyl acetate (3% of pheromone), was always much
      greater than the titer of the FAPA of the major component, (Z)-11-tetradecenyl
      acetate (97%), of the pheromone. Titer of myristate, an intermediate in pheromone
      biosynthesis, was also higher during the scotophase than the photophase. However,
      myristate titer showed a pronounced dip in the middle of the scotophase. These
      data suggest two roles for glandular lipids in sex pheromone biosynthesis in O.
      nubilalis. Firstly, they remove excess FAPA of the minor component so the fatty
      acid reductase system is not presented with a high ratio of this isomer (which
      would otherwise result from the reductase's own selectivity), which could cause
      changes in the final pheromone ratio. Secondly, hydrolysis of the large amounts
      of stored saturated fatty acids from the TGs may provide substrate for pheromone
      biosynthesis.

PMID- 15146541
TI  - cDNA cloning, expression, and characterization of an arylphorin-like hexameric
      storage protein, AgeHex2, from the mulberry longicorn beetle, Apriona germari.
AB  - An arylphorin-like hexameric storage protein, AgeHex2, cDNA was cloned from the
      mulberry longicorn beetle, Apriona germari (Coleoptera, Cerambycidae), larval
      cDNA library. The complete cDNA sequence of AgeHex2 is comprised of 2,088 bp
      encoding 696 amino acid residues. The AgeHex2 had four potential N-glycosylation
      sites. The AgeHex2 contained the highly conserved two larval storage protein
      signature motifs. The deduced protein sequence of AgeHex2 showed high homology
      with A. germari hexamerin1 (51% amino acid identity), Tenebrio molitor hexamerin2
      (49% amino acid identity), T. molitor early-staged encapsulation inducing protein
      (43% amino acid identity), and Leptinotarsa decemlineata diapause protein1 (43%
      amino acid identity). Phylogenetic analysis further confirmed the AgeHex2 is more
      closely related to coleopteran hexamerins than to the other insect storage
      proteins. Northern blot analysis confirmed that the AgeHex2 showed fat body
      specific expression. The cDNA encoding AgeHex2 was expressed as a 75-kDa protein
      in the baculovirus-infected insect cells. Furthermore, N-glycosylation of the
      recombinant AgeHex2 was revealed by tunicamycin to the recombinant virus-infected
      Sf9 cells, demonstrating that the AgeHex2 is N-glycosylated. Western blot
      analysis using the polyclonal antiserum against recombinant AgeHex2 indicated
      that the AgeHex2 corresponds to a 75-kDa storage protein present in the A.
      germari larval hemolymph.

PMID- 15146543
TI  - Mechanisms of the insecticidal action of TEL (Talisia esculenta lectin) against
      Callosobruchus maculatus (Coleoptera: Bruchidae).
AB  - Plant lectins have insecticidal activity that is probably mediated through their
      ability to bind carbohydrates. To examine the influence of sugars on the
      insecticidal activity of a lectin from Talisia esculenta seeds (TEL), the lectin
      was mixed with mannose, glucose, or mannose plus glucose. Mannose abolished the
      insecticidal activity. Affinity chromatography showed that TEL bound to midgut
      proteins of the insect Callosobruchus maculatus. Immunoblotting showed that TEL
      recognized some proteins, probably glycoproteins, present in the midgut membrane
      of this insect. The principal proteases responsible for digestive proteolysis in
      fourth instar larvae of C. maculatus were purified by chromatography on activated
      thiol-Sepharose. These purified proteases were unable to digest TEL after a 15-h
      incubation. These results suggest that the insecticidal activity of TEL involves
      a specific carbohydrate-lectin interaction with glycoconjugates on the surface of
      digestive tract epithelial cells, as well as binding to assimilatory
      glycoproteins present in midgut extracts and resistance to enzymatic digestion by
      cysteine proteinases.

PMID- 15146544
TI  - Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar
      granule cells.
AB  - Pycnogenol (PYC), a patented combination of bioflavonoids extracted from the bark
      of French maritime pine (Pinus maritima), scavenges free radicals and promotes
      cellular health. The protective capacity of PYC against ethanol toxicity of
      neurons has not previously been explored. The present study demonstrates that in
      postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE)
      and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL
      ethanol exposure (2) inhibit the ethanol-induced activation of caspase-3 in the
      same model system; and (3) reduce neuronal membrane disruption as assayed by
      phosphatidylserine translocation to the cell surface. These results suggest that
      both PYC and VE have the potential to act as therapeutic agents, antagonizing the
      induction of neuronal cell death by ethanol exposure.

PMID- 15146545
TI  - Expression of functional kainate and AMPA receptors in developing lateral
      superior olive neurons of the rat.
AB  - A functional analysis of AMPA and kainate receptors (AMPARs and KARs) in the
      lateral superior olive (LSO), a major nucleus in the auditory brainstem, has not
      been performed so far, to our knowledge. Here we investigated the presence and
      characteristics of such receptors in the rat LSO by means of whole-cell patch
      clamp recordings in combination with pharmacology. Current responses evoked by
      200 microM AMPA were completely blocked by the specific AMPAR antagonist GYKI
      52466 (100 microM). Properties of the AMPAR-mediated currents (latency,
      activation time constant, and peak amplitude) remained constant between postnatal
      day 3 (P3) and P10. Current responses evoked by 100 microM KA were not completely
      blocked by 100 microM GYKI 52466, indicating that the residual component was
      mediated by KARs. Throughout development, two groups of KAR-mediated currents
      (fast I(KA) and slow I(KA)) were distinguished because they had significantly
      different mean activation time constants. Moreover, the mean peak amplitude of
      fast I(KA) was significantly higher than that of slow I(KA). The differentiation
      into fast I(KA) and slow I(KA) can be explained by the existence of two groups of
      LSO neurons displaying different KAR densities, distributions, and/or diverse
      types with differences in conductance. Application of the specific KAR subunit
      agonists SYM 2081 (10 microM), ATPA (10 microM), or iodowillardiine (1 microM)
      evoked currents in almost all cells tested, showing that GluR5 subunits are a
      component of functional KARs in LSO neurons. Electrical stimulation of
      ipsilateral input fibers in the presence of KAR antagonists (NS-102 and GAMS),
      modulators (WGA), or GYKI 52466 revealed the presence of synaptic KARs in LSO
      neurons.

PMID- 15146546
TI  - Beak gape dynamics during song in the zebra finch.
AB  - Bird song is a complex communication behavior that requires the coordination of
      several motor systems. Sound is produced in the syrinx and then modified by the
      upper vocal tract, but the specific nature and dynamics of this modification are
      not well understood. To determine the contribution of beak movements to sound
      modification, we studied the beak gape patterns in zebra finches (Taeniopygia
      guttata). Subsyringeal air sac pressure and song were recorded together with
      changes in beak gape, which were monitored with a magneto-sensitive transducer.
      Beak gape was positively correlated with fundamental frequency, peak frequency,
      and subsyringeal air sac pressure in all but one bird. For harmonic stacks, peak
      frequency increased with increasing beak gape, and the relationship between
      fundamental frequency and beak gape was no longer significant. Experimentally
      holding the beak open or closed had acoustic consequences consistent with the
      model in which beak movements change upper vocal tract length and, thus, the
      filter properties. Beak gape was positively correlated with sound amplitude in
      all but two birds. The relationship between beak aperture and amplitude may,
      however, be indirect because air sac pressure is correlated with amplitude and
      beak gape. The beak is opened quickly and to its widest aperture immediately
      prior to the onset of sound and at rapid transitions in sound, suggesting that
      beak movements may affect vibratory behavior of the labia.

PMID- 15146547
TI  - Modulation of two oscillatory networks in the peripheral olfactory system by
      gamma-aminobutyric acid, glutamate, and acetylcholine in the terrestrial slug
      Limax marginatus.
AB  - The digit-like extensions (the digits) of the tentacular ganglion of the
      terrestrial slug Limax marginatus are the cell body rich region in the primary
      olfactory system, and they contain primary olfactory neurons and projection
      neurons that send their axons to the olfactory center via the tentacular nerves.
      Two cell clusters (the cell masses) at the bases of the digits form the other
      cell body rich regions. Although the spontaneous slow oscillations and odor
      responses in the tentacular nerve have been studied, the origin of the
      oscillatory activity is unknown. In the present study, we examined the
      contribution of the neurons in the digits and cell masses to generation of the
      tentacular nerve oscillations by surgical removal from the whole tentacle
      preparations. Both structures contributed to the tentacular oscillations, and
      surgical isolation of the digits from the whole tentacle preparations still
      showed spontaneous oscillations. To analyze the dynamics of odor-processing
      circuits in the digits and tentacular ganglia, we studied the effects of gamma
      aminobutyric acid, glutamate, and acetylcholine on the circuit dynamics of the
      oscillatory network(s) in the peripheral olfactory system. Bath or local puff
      application of gamma-aminobutyric acid to the cell masses decreased the
      tentacular nerve oscillations, whereas the bath or local puff application of
      glutamate and acetylcholine to the digits increased the digits' oscillations. Our
      results suggest the existence of two intrinsic oscillatory circuits that respond
      differentially to endogenous neurotransmitters in the primary olfactory system of
      slugs.

PMID- 15146548
TI  - Tracheal length changes during zebra finch song and their possible role in upper
      vocal tract filtering.
AB  - Sounds produced in the avian vocal organ may be modified by filter properties of
      the upper vocal tract. Possible mechanisms to actively control filter
      characteristics include movements of the beak, tongue, and larynx and adjustments
      of tracheal length. We investigated whether length changes of the trachea are a
      likely mechanism for adjusting upper vocal tract filter properties during song in
      the zebra finch (Taeniopygia guttata). Tracheal length was monitored at the basal
      end using sonomicrometry and was recorded together with subsyringeal air sac
      pressure and acoustic output. Tracheal shortening occurred at the onset of song
      bouts, and during each motif the tracheal length decreased during expiratory
      pressure pulses and increased during the short inspirations. A bilateral tracheal
      syringeal nerve cut confirmed that the initial shortening at the onset of the
      song bout is an active shortening of the trachea (i.e., mediated by syringeal
      muscle activity). The modulation of length during the motif was not affected by
      the denervation and is most likely driven by the pressurization of the
      interclavicular air sac. The absolute length change during the motif was small
      (<0.2 mm) and not clearly related to acoustic features of the song. For example,
      some high-frequency syllables, which are generated during inspiration, were
      accompanied by tracheal elongation. Because this elongation shifts tube
      resonances to lower frequencies, it is inconsistent with an active adjustment of
      length to enhance high frequency sounds. The small magnitude and inconsistent
      nature of dynamic tracheal length changes during song make it unlikely that they
      significantly affect vocal tract filter properties if the trachea is modeled as a
      rigid tube.

PMID- 15146549
TI  - Nitric oxide modulates presynaptic afferent depolarization of mechanosensory
      neurons.
AB  - In crayfish, movement of the tailfan causes stimulation of exteroceptive sensory
      hairs located on its surface. Movement is monitored by a proprioceptor, the
      protopodite-endopodite chordotonal organ within the tailfan. Proprioceptive
      afferents provide indirect presynaptic inhibitory inputs to sensory hair
      afferents in the form of primary afferent depolarizations (PADs). Bath
      application of nitric oxide (NO) substrates, donors and scavengers, and nitric
      oxide synthase (NOS) inhibitors had no effect on the responses of proprioceptive
      afferents during imposed movements of the chordotonal organ. In contrast, the
      amplitude of PADs in exteroceptive hair afferents was dependent on NO levels. NO
      levels were altered by bath-application of the NO-precursor L-arginine, the NO
      donor SNAP, the NOS-inhibitor L-NAME, and the NO scavenger PTIO, while changes in
      PAD amplitude were measured. Application of L-arginine or SNAP resulted in
      consistent decreases in PAD amplitude, whereas L-NAME and PTIO induced increases
      in PAD amplitude. These results suggest that endogenous NO decreases inhibitory
      inputs to exteroceptive neurons, thus enhancing transmitter release at their
      output synapses.

PMID- 15146550
TI  - Characterization of salvicine-resistant lung adenocarcinoma A549/SAL cell line.
AB  - Salvicine is a diterpenoid quinone derived from a traditional Chinese medication
      that has been shown to possess potent in vitro and in vivo antitumor effects.
      This compound, which inhibits the activity of Topoisomerase II, was found to
      equipotently kill various multidrug-resistant tumor cells and their corresponding
      parental counterparts in vitro and to inhibit mdr1/P-gp expression in multidrug
      resistant K562/A02 cells. To examine the features of tumor resistance to
      salvicine, we established a salvicine-resistant tumor cell subline of A549 lung
      adenocarcinoma cells. Compared with parental cells, A549/SAL cells displayed 8.91
      fold resistance to salvicine and an average of 6.70-fold resistance to the
      antimetabolites. A549/SAL cells, however, were not resistant to alkylating
      agents, platinum compounds and other naturally-derived antineoplastics. RT-PCR
      analysis showed that the expression of mRNAs from the mdr-1, MRP, PCNA,
      topoisomerase II alpha and beta, GSTpi, p21 and GADD45 genes was not altered in
      the salvicine-resistant subline. In contrast, expression of p53 and bax mRNA was
      significantly lower, and expression of mdm2 mRNA was significantly higher, in
      A549/SAL cells compared to A549 cells. A549/SAL cells grew more slowly, and in a
      more scattered pattern, than A549 cells. In addition, the A549/SAL cells showed
      enhanced ability to migrate and invade in comparison to the parental cells. These
      results indicate that exposure to salvicine does not induce a tumor multidrug
      resistant phenotype.

PMID- 15146552
TI  - Inhibitory effects of evodiamine on the growth of human prostate cancer cell line
      LNCaP.
AB  - Evodiamine, isolated from a Chinese herbal drug named Wu-Chu-Yu, possesses many
      biological functions. Recently, it has been reported that Wu-Chu-Yu exerts an
      antiproliferative effect on several cancers. Prostate carcinoma initially occurs
      as an androgen-dependent tumor and is the second leading cause of cancer death in
      American males. In the present study, the effect of evodiamine on the growth of
      androgen-dependent prostate cancer cell line LNCaP in vitro was examined. Based
      on [3-(4,5-dimethylthiazol-2-yle)2,5-diphenyltetrazolium bromide] (MTT) assay,
      evodiamine significantly inhibited the growth of LNCaP cells in a concentration
      dependent manner. A significant and concentration-dependent inhibitory effect of
      evodiamine on LNCaP cell growth was observed at 24 hr and persisted for 96 hr.
      The examination of lactate dehydrogenase (LDH) assay showed that the cytotoxic
      effects of evodiamine on LNCaP cells were concentration dependent. Furthermore,
      we examined the influences of evodiamine on cell death and cell cycle. The flow
      cytometric analysis of evodiamine-treated cells indicated a block of G2/M phase
      and an elevated level of DNA fragmentation. The G2/M arrest reached a maximum at
      24 hr after evodiamine treatment. The G2/M arrest was accompanied by an elevated
      p34(cdc2) kinase activity and an increase in the protein expression of cyclin B1
      and phosphorylated form of p34(cdc2) (Thr 161). Examination of TUNEL showed that
      evodiamine-induced apoptosis was observed at 24 hr and extended for 72 hr.
      Evodiamine elevated caspase-3, and caspase-9 activities and the processing of
      caspase-3 and caspase-9. These results suggested that evodiamine inhibits the
      growth of prostate cancer cell line, LNCaP, through an accumulation of cell cycle
      at G2/M phase and an induction of apoptosis.

PMID- 15146551
TI  - Pregnancy-associated plasma protein-A (PAPP-A) expression and insulin-like growth
      factor binding protein-4 protease activity in normal and malignant ovarian
      surface epithelial cells.
AB  - Pregnancy-Associated Plasma Protein-A (PAPP-A) proteolyses insulin-like growth
      factor binding protein-4 (IGFBP-4), thereby regulating local IGF availability.
      Reduced PAPP-A mRNA expression has been reported in ovarian cancer specimens
      compared to normal ovarian surface epithelial cells (OSE). To characterize PAPP-A
      expression and proteolytic activity in OSE, we developed a lifespan-extended
      human cell model using a temperature-sensitive mutant of the SV40 large T antigen
      (SV40LT). These OSE(tsT) cells proliferate at 34 degrees C (i.e., when SV40LT
      positive), but not at 39 degrees C, a temperature at which the SV40LT is unstable
      (SV40LT-negative). Proteolysis of radiolabeled IGFBP-4 in conditioned media from
      OSE(tsT) lines was IGF-dependent and blocked by anti-PAPP-A antisera. Temperature
      shifts that eliminated stable SV40LT induced a 7-fold increase in PAPP-A mRNA and
      a 4-fold increase in protein. The converse experiment (shifting to SV40LT
      positive conditions) resulted in decreased levels of PAPP-A mRNA but little
      change in PAPP-A protein. Nevertheless, there was a marked reduction in IGF-BP-4
      proteolytic activity in medium of SV40LT-positive OSE-(tsT) cells. This decreased
      PAPP-A activity coincided with a nearly 20-fold increase in mRNA encoding a
      physiological inhibitor of PAPP-A, the precursor form of eosinophil Major Basic
      Protein (proMBP), and 4- to 5-fold increases in proMBP protein. Primary cultures
      of unmodified OSE expressed high levels of PAPP-A and undetectable proMBP, and
      therefore produced abundant IGFBP-4 protease activity. Short-term ovarian tumor
      cell cultures expressed variable levels of PAPP-A and high levels of proMBP, and
      consequently secreted little or no IGFBP-4 protease activity. The concurrent
      regulation of PAPP-A and its inhibitor, proMBP, suggests that IGFBP-4 proteolysis
      and local regulation of IGF availability may be altered in malignant ovarian
      epithelial cells.

PMID- 15146553
TI  - Stromal cell-derived factor-1alpha-induced cell proliferation and its possible
      regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma.
AB  - CD26/dipeptidylpeptidase IV (DPPIV) is a 110 kD membrane-bound extracellular
      peptidase with ubiquitous expressions, and has a variety of functional properties
      in the development of human malignancies as well as T-cell biology. According to
      recent reports, stromal cell derived factor-1alpha (SDF-1alpha), which is a good
      substrate for CD26/DPPIV, is expressed in various solid tumors and is involved in
      tumor development or metastasis. We investigated the expression of SDF-1alpha and
      its corresponding receptor, CXCR4, in human endometrial carcinoma (EMCA) tissues
      and the function of SDF-1alpha on EMCA cells with its regulation by CD26/DPPIV.
      We demonstrated that SDF-1alpha and CXCR4 were expressed in human EMCA, and these
      immunoreactivities were significantly low in Grade 3 EMCA, which was similar to
      that of CD26/DPPIV, compared to those in Grade 1 and Grade 2. Additionally,
      exogenous SDF-1alpha concentration was significantly lower in CD26/DPPIV
      transfected EMCA cells than that in vector-transfected cells. Moreover, exogenous
      SDF-1alpha significantly stimulated cell proliferation in vector-transfected
      cells in a concentration dependent manner. In contrast, in CD26/DPPIV-transfected
      cells, there was no apparent effect on proliferation shown by the addition of
      exogenous SDF-1alpha. This is the first report showing a direct link between the
      SDF-1alpha/CXCR4 pathway with CD26/DPPIV in solid tumors, suggesting that
      CD26/DPPIV is likely to directly modulate various SDF-1alpha induced functions.

PMID- 15146554
TI  - Increased adenoviral transduction efficacy in human laryngeal carcinoma cells
      resistant to cisplatin is associated with increased expression of integrin
      alphavbeta3 and coxsackie adenovirus receptor.
AB  - In our study, we investigated molecular mechanisms of increased adenoviral
      transduction efficacy in cisplatin-resistant human laryngeal carcinoma cells
      CA3ST as compared to parental cells HEp2. Using reverse transcription-PCR, the
      genes potentially implicated in adenoviral entry were screened. In cisplatin
      resistant cells, only upregulation of alphavbeta3 integrin was detected, which
      was additionally confirmed by flow cytometry. Moderately increased expression of
      CAR was determined in cisplatin-resistant CA3ST cells using flow cytometry and
      measurement of wild-type adenovirus Ad5CMVbetagal attachment. In order to test
      the implication of alphavbeta3 integrin in transduction efficacy, 6 HEp2-derived
      alphavbeta3-expressing clones with graded expression of alphavbeta3 were
      isolated. To a certain degree of density, expression of alphavbeta3 positively
      correlated with Ad5CMVbetagal transduction efficacy (i.e., increased viral
      transduction), suggesting a role of alphavbeta3 in transduction efficacy.
      However, HEp2 clones with the highest alphavbeta3) expression were negatively
      correlated with transduction efficacy (i.e., decreased viral transduction). This
      was shown to be associated with downregulation of alphavbeta5 integrin, also
      involved in viral transduction, in clones with the highest alphavbeta3
      expression. The implication of CAR in increased adenoviral transduction efficacy
      in cisplatin resistant CA3ST cells was further assessed by transduction
      experiments using adenoviral mutant Ad5FbDelta639 whose entry is only to a very
      small extent dependent on the presence of CAR. Indeed, Ad5FbDelta639 infected 2.5
      fold more, in comparison to wild-type adenovirus, which infected 5-fold more
      efficiently resistant CA3ST cells than parental HEp2 cells, indicating that
      increased expression of CAR contributes to increased efficacy of adenoviral
      transduction. Thus, the data presented provide evidence that both alphavbeta3
      integrin and CAR are involved in increased adenoviral transduction efficacy in
      cisplatin resistant CA3ST cells. These findings may have significant implications
      in human gene therapy using adenoviruses, especially in patients after
      unsuccessful cisplatin treatment.

PMID- 15146555
TI  - Indian hedgehog signaling pathway: expression and regulation in pancreatic
      cancer.
AB  - Pancreatic cancer is an aggressive malignancy that exhibits a number of genetic
      and epigenetic alterations. Indian hedgehog (Ihh) and its 2 signaling receptors,
      patched (Ptc) and smoothened (Smo), are involved in pancreatic development and
      regulation of beta-cell function as well as in certain human tumors. In the
      current study, we analyzed the expression, distribution and function of Ihh and
      its receptors in pancreatic cancer. Quantitative RT-PCR and immunohistochemistry
      were utilized to analyze the expression, localization and transcriptional
      regulation of Ihh, Ptc and Smo. The effects of inhibition and stimulation of the
      hedgehog signaling pathway on pancreatic cancer cell growth were examined by the
      MTT cell growth assay. By quantitative RT-PCR, Ihh, Ptc and Smo mRNA levels were
      increased 35-, 1.2- and 1.6-fold, respectively, in pancreatic cancer tissues in
      comparison to normal pancreatic tissues. By immunohistochemistry, Ihh, Ptc and
      Smo were expressed in the islet cells of normal and cancerous tissues and in
      pancreatic cancer cells. The growth of pancreatic cancer cells was dose
      dependently inhibited by the hedgehog antagonist cyclopamine through G0/G1
      arrest. In contrast, Ihh agonists exhibited no significant effect on pancreatic
      cancer cell growth. TGF-beta1 repressed Ihh transcription in a TGF-beta1
      responsive pancreatic cancer cell line, but had no effect on the other tested
      cell lines. In conclusion, Ihh and its receptors Ptc and Smo are expressed in
      pancreatic cancer, and blockage of hedgehog signaling results in inhibition of
      pancreatic cancer cell growth, suggesting that aberrant activation of the Ihh
      signaling pathway contributes to tumor development in this malignancy.

PMID- 15146556
TI  - BRCA1 mutations in South African breast and/or ovarian cancer families: evidence
      of a novel founder mutation in Afrikaner families.
AB  - Germ-line mutations within BRCA1 are responsible for different proportions of
      inherited susceptibility to breast/ovarian cancer, and the spectrum of mutations
      within this gene is often unique to certain populations. At this time, there have
      been no reports regarding the role of BRCA1 in South African breast and/or
      ovarian cancer families. We therefore screened 90 South African breast/ovarian
      cancer families for BRCA1 mutations by means of PCR-based mutation detection
      assays. Eighteen families (20%) were identified with BRCA1 disease-causing
      mutations. Four Ashkenazi Jewish families were identified with the 185delAG
      mutation, whereas 2 Afrikaner and 1 Ashkenazi Jewish family were found to harbor
      the 5382insC mutation. Five of the families (5.56%), all of whom are Afrikaners,
      were found to carry the novel E881X mutation. Genotype analyses show that these
      patients share a common ancestor. Genealogic studies have identified 3 possible
      founding couples for this mutation, all of whom arrived in the Cape from France
      in the late 1600s. Of the remaining mutations detected, 3 have not been reported
      previously and include the S451X, 1493delC (detected twice) and 4957insC
      mutations.

PMID- 15146557
TI  - A high proportion of founder BRCA1 mutations in Polish breast cancer families.
AB  - Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and
      account for the majority of mutations identified to date in Polish breast and
      breast-ovarian cancer families. It is not known, however, to what extent these 3
      founder mutations account for all of the BRCA mutations distributed throughout
      the country. This question has important implications for health policy and the
      design of epidemiologic studies. To establish the relative contributions of
      founder and nonfounder BRCA mutations, we established the entire spectrum of
      BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with
      origins in all regions of Poland. We sequenced the entire coding regions of the
      BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast
      cancer and in 100 families with cases of both breast and ovarian cancer. A
      mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in
      63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in
      BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119
      (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2
      families). In particular, 111 families (91.0%) carried one of the 3 common
      founder mutations. The mutation spectrum was not different between families with
      and without ovarian cancer. These findings suggest that a rapid and inexpensive
      assay directed at identifying the 3 common founder mutations will have a
      sensitivity of 86% compared to a much more costly and labor-intensive full
      sequence analysis of both genes. This rapid test will facilitate large-scale
      national epidemiologic and clinical studies of hereditary breast cancer,
      potentially including studies of chemoprevention.

PMID- 15146558
TI  - Profiling and functional annotation of mRNA gene expression in pediatric
      rhabdomyosarcoma and Ewing's sarcoma.
AB  - Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression
      patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas
      (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic
      classification of these cancers is frequently complicated by the highly similar
      appearance in routine histology, and additional molecular markers could
      significantly improve tumor classification. A combination of three independent
      statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in
      101 highly significant probe sets that clearly discriminate between EWS and RMS.
      We identified novel marker transcripts that have not been previously associated
      with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1
      (CCND1). Expression levels for selected candidate genes were validated by
      quantitative real-time reverse-transcription PCR. Furthermore, to identify
      biologically meaningful trends, functional annotations were assigned to 946 genes
      differentially expressed between EWS and RMS (t-test). Genes involved in protein
      biosynthesis (n = 28) and complex assembly (n = 9), lipid metabolism (n = 23),
      energy generation (n = 22), and mRNA processing (n = 11) were expressed
      significantly higher in EWS. Thus, functional annotation of tumor-specific genes
      reveals detailed insights into tumor biology and differentiation-specific
      expression patterns and gives important clues related to the possible cellular
      origin of these pediatric tumors. Supplementary material for this article is
      available at the International Journal of Cancer website at
      http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

PMID- 15146559
TI  - Promoter polymorphisms of tumor necrosis factor-alpha are associated with risk of
      gastric mucosa-associated lymphoid tissue lymphoma.
AB  - Genes involved in regulating antimicrobial immunity and inflammation may modulate
      the risk of Helicobacter pylori-associated diseases. IL-1 and TNF-alpha are major
      cytokines detected in H. pylori-infected tissues. We aimed to determine the role
      of gene polymorphisms for these cytokines and their receptors in 2 distinct H.
      pylori-related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping
      for IL-1beta (-31 C/T, -511 C/T), TNF-alpha (-238 G/A, -308 G/A, -857 C/T, -863
      C/A, -1031 T/C), TNFR1 (-383 A/C) and TNFR2 (196 G/T) was undertaken for 70
      patients with maltoma and 204 patients with noncardia GAC and compared to 210
      unrelated healthy controls. Genotype frequencies showed no differences among
      patients with GAC or maltoma and controls for IL-1beta, TNFR1 or TNFR2. The TNF
      alpha -857 T variant was significantly underrepresented in maltoma compared to
      controls (6.4% vs. 14.3%, p = 0.018), conferring a 3-fold decrease in risk (OR =
      0.33, 95% CI 0.15-0.75). Comparison of allele frequencies between GAC and
      controls failed to show any statistical significance for TNF-alpha polymorphisms.
      We concluded that TNF-alpha -857 T itself or a neighboring gene may modify the
      risk of maltoma. The differences in genetic background as well as divergent
      clinicopathologic features between GAC and maltoma support the notion that
      fundamental mechanistic differences exist in these 2 well-defined H. pylori
      related malignancies.

PMID- 15146560
TI  - Mapping and analysis of HPV16 integration sites in a head and neck cancer cell
      line.
AB  - Human papillomavirus (HPV) is a circular double-stranded DNA virus implicated in
      at least 90% of cervical and anogenital cancers and has been observed in
      approximately 20% of squamous cell carcinomas of the head and neck (SCCHN).
      Transcription of the viral oncogenes E6 and E7 is regulated by expression of the
      E2 protein. Disruption of the E2 gene sequence due to viral integration results
      in upregulation of E6 and E7, which promote tumorigenesis by abrogating p53 and
      pRb functions. HPV integration sites in cervical and anogenital cancers have been
      mapped primarily to chromosomal fragile sites and in some cases have been shown
      to integrate within tumor suppressor genes or other cancer-related genes. To
      study viral integration sites in SCCHN, we examined an HPV16-infected SCCHN cell
      line cultured from a tongue-base tumor. HPV fluorescence in situ hybridization
      (FISH) revealed multiple integrated viral DNA copies in blocks throughout the
      genome. Sequential FISH and spectral karyotyping identified integration sites on
      chromosomes 3, 6, 9q, 13q and t(1;8)(q;?). Restriction site-polymerase chain
      reaction (RS-PCR) was performed to identify the viral-cellular junctions.
      Sequence analyses confirmed integration sites at 9q31.1 and 6p21 and revealed a
      novel junction at 16p12.3. Subsequent chromosome breakage studies suggested that
      the observed viral-cellular integration sites may have occurred within common
      fragile sites. Additional studies using RT-PCR for E6--E7 viral transcripts
      showed oncoprotein expression from episomal and integrated viral sequences. Our
      results suggest that viral integration of HPV in SCCHN appears to occur
      nonrandomly through targeting specific chromosomal sequences prone to breakage.

PMID- 15146562
TI  - Blood T-cell Vbeta transcriptome in melanoma patients.
AB  - Tumor-cells have been shown to elicit MHC-restricted and antigen-specific T-cell
      responses. In this article, we used a new approach to study T-cell responses in
      tumor-bearing patients based on a global representation of the Vbeta
      transcriptome, making it possible to grade CDR3-length distribution (CDR3-LD)
      alterations. Six patients with advanced melanoma disease, from whom blood samples
      were taken before and serially after tyrosinase-A peptide vaccination, were
      studied. The PBMC from patients displayed highly significant Vbeta transcriptome
      alterations as compared to healthy individuals. Similar Vbeta alterations could
      be detected both in PBMCs and at the tumor site. After vaccination, Vbeta
      alterations could also be observed by gauging individually their transcript level
      but not their cell-surface expression. Some Vbeta families exhibited high
      Vbeta/HPRT transcript ratios (e.g., Vbeta1), which represented up to 44% of the
      whole transcriptome, a situation that was not reflected by an increase in the
      percentage of T cells that expressed the corresponding protein and was not
      observed in normal individuals. In several instances, CDR3-LD altered T cells
      exhibited MHC-restricted and tumor-specific IFNgamma or GM-CSF production.
      Finally, we show that the presence of a tumor and probably vaccination can affect
      Vbeta transcriptome patterns and induce specific clones reactive to autologous
      tumor or vaccinating peptides. In combination with other methods, such an
      approach should help in identifying the clones actually involved in the response
      against the tumor.

PMID- 15146561
TI  - Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2
      different subpopulations of dendritic cells with CD1a(high)CD86(-)Langerin- and
      CD1a(+)CD86(+)Langerin+ phenotypes.
AB  - Primary breast carcinoma are frequently infiltrated by dendritic cells (DC). The
      mechanisms involved in the localization and status of activation of DC within
      primary breast carcinoma were investigated. CCL20/MIP3alpha, a chemokine involved
      in immature DC and their precursors attraction, was detected by
      immunohistochemistry on cryopreserved tissue sections of primary breast tumors
      and by ELISA and biological assay in metastatic effusion fluids from breast
      cancer patients but not from other tumors. In vitro, irradiated breast carcinoma
      cell lines (BCC) as well as their conditioned media promoted CD34+ cell
      differentiation into CD1a+ Langerhans cells (LC) precursors as early as day 6,
      while at day 12, 2 different CCR6+ subpopulations of DC with a Langerhans cell
      (CD1a(+)Langerin(+)CD86+) and an immature DC (CD1a(high)Langerin-CD86(-)HLA
      DR(low)CD40(low)) phenotype were observed. This phenomenon was partly driven by a
      TGFbeta-dependent mechanism since a pan TGFbeta polyclonal antibody completely
      blocks BCC-induced LC differentiation and partly reduces immature DC development.
      These DC failed to maturate in response to sCD40L or LPS stimuli and
      CD1a(high)Langerin(-)CD86- cells have a reduced T-cell stimulatory capacity in
      MLR experiments. The absolute number of T cells was reduced by 50% in both the
      CD4+ or CD8+ compartments, these T cells expressing lower levels of the CD25 Ag
      and producing less IFNgamma. These results show that breast carcinoma cells
      produce soluble factors, which may attract DC and their precursors in vivo, and
      promote the differentiation of the latter into LC and immature DC with altered
      functional capacities. The infiltration of BCC by these altered DC may contribute
      to the impaired immune response against the tumor.

PMID- 15146563
TI  - Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T
      cell and clinical responses in melanoma stage III and IV patients.
AB  - Hybrid cell vaccination was developed as therapeutic approach that aims at
      stimulating tumor-specific cytotoxic T-cell responses in cancer patients using
      hybrids of autologous tumor and allogeneic dendritic cells. We tested this
      concept and the efficacy of the vaccines in inducing clinical and immunologic
      responses in a clinical trial with melanoma stage III and IV patients. Of the 17
      patients evaluated, 1 experienced a complete response, 1 a partial response and 6
      stable disease with remarkably long survival times. In 11 of 14 patients
      analyzed, high-frequency T-cell responses to various tumor-associated T-cell
      epitope were induced and detectable in the peripheral blood. These immune
      responses were detected in clinical response patients as well as nonresponders.
      Failures of clinical responses in all the cases investigated correlated with loss
      of antigen expression and presentation. Hybrid cell vaccination thus proves
      effective in inducing tumor-specific T-cell responses in cancer patients.

PMID- 15146564
TI  - Receptor for the globular heads of C1q (gC1q-R, p33, hyaluronan-binding protein)
      is preferentially expressed by adenocarcinoma cells.
AB  - Combinatorial Ig libraries with phage display allow in vitro generation of human
      Ig fragments without the need to maintain hybridomas in ongoing cell culture or
      to select circulating Ig from human serum. Identifying tumor-associated antigens
      on the surface of intact tumor cells, as opposed to purified proteins, presents a
      challenge due to the difficulty of preserving complex 3-D epitopic sites on the
      cell surface, the variable expression of antigens on different malignant cell
      types and the stereotactic interference of closely associated proteins on the
      intact membrane surface limiting accessibility to antigenic sites. A
      combinatorial Ig library of 10(10) clones was generated from the cDNA of PBMCs
      derived from patients with breast adenocarcinoma. Following subtractive panning,
      the library was enriched for Ig (Fab fragment) binding to intact adenocarcinoma
      cells and the resultant Fabs were screened against a cDNA expression library,
      itself generated from breast cancer cells. Using this approach, we isolated
      clones from the cDNA library expressing gC1q-R, a glycoprotein comprising the
      major structure of C1, the first component of the complement system. gC1q-R is a
      33 kDa glycoprotein expressed not only on the cell surface but also
      intracellularly, with motifs that target it to mitochondria and complete homology
      with HABP and human HeLa cell protein p32, which is copurified with pre-mRNA SF2.
      Sequencing of the gene encoding tumor-associated gC1q-R did not reveal any
      consistent tumor-specific mutations. However, histochemical staining with anti
      gC1q-R MAb demonstrated marked differential expression of gC1q-R in thyroid,
      colon, pancreatic, gastric, esophageal and lung adenocarcinomas compared to their
      nonmalignant histologic counterparts. In contrast, differential expression was
      not seen in endometrial, renal and prostate carcinomas. Despite high expression
      in breast carcinoma, gC1q-R was also expressed in nonmalignant breast tissue.
      Although the precise relation of gC1q-R to carcinogenesis remains unclear, our
      finding of tumor overexpression and the known multivalent binding of gC1q-R to
      not only C1q itself but also a variety of circulating plasma proteins as well as
      its involvement in cell-to-cell interactions suggest that gC1q-R may have a role
      in tumor metastases and potentially serve in molecule-specific targeting of
      malignant cells.

PMID- 15146565
TI  - Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial
      aspirates from patients with suspected lung cancer.
AB  - Promoter hypermethylation is a major mechanism for gene silencing and offers a
      promising starting point for developing molecular biomarkers. The purpose of our
      study was to determine aberrant methylation of the adenomatous polyposis coli
      (APC) gene promoter 1A with respect to its prevalence and quantitative level in
      bronchial aspirates from patients with suspected lung cancer. Applying
      quantitative methylation-specific PCR, 155 bronchial aspirates from patients with
      non-small cell cancer (NSCLC) and small cell cancer (SCLC) of the lung as well as
      67 bronchial aspirates from patients diagnosed for nonneoplastic lung disease
      were examined in a retrospective case-control study. Aberrant APC promoter 1A
      methylation was seen in 71% of NSCLCs, 38% of SCLCs and 42% of patients with
      nonneoplastic lung disease, being therefore not specific for the presence of
      primary lung cancer. In contrast, quantitative analysis showed a significantly
      higher methylation level of bronchial aspirates from NSCLC as compared to
      patients without neoplastic lung disease. Introducing a cutoff point that defined
      high level of APC hypermethylation NSCLC could be discriminated from cases
      without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%.
      The data suggest that quantitative analysis of APC hypermethylation may serve as
      a biomarker of primary lung cancer.

PMID- 15146566
TI  - Mammography benefit in the Canadian National Breast Screening Study-2: a model
      evaluation.
AB  - The CNBSS-2 among women aged 50-59 did not show any significant difference in
      breast cancer mortality between a control arm screened annually by CBE and a
      study arm screened by CBE and mammography. Because of this design, the benefit of
      screening compared to no screening could not be evaluated. We therefore conducted
      a modeling effort to estimate the benefit of mammography or CBE compared to no
      screening. We incorporated demographic, epidemiologic and screening
      characteristics of the CNBSS-2 in MISCAN. Stage-specific sensitivities of CBE,
      with and without mammography, and breast cancer incidence rate in the trial were
      estimated by comparing observed trial data with model predictions. We predicted
      the number of breast cancer deaths for both study arms of the CNBSS-2 and in the
      absence of screening, assuming improvement in prognosis by early detection. We
      estimated a 24-29% higher breast cancer incidence rate in the CNBSS-2 than the
      average Canadian rate. Estimated sensitivity of CBE (control arm) varied from
      0.29 to 0.48 for stage T1c and from 0.6 to 0.65 for stage T2+. Estimated
      sensitivity of CBE supplemented with mammography (study arm) varied from 0.5 to
      0.79 for stage T1c and was 0.95 for stage T2+. Expected breast cancer mortality
      reduction by annual CBE screening is 20.5% compared to no screening. Estimated
      breast cancer mortality reduction by mammography screening compared to no
      screening for the CNBSS-2 fell within the range 13.6-34.1%. Enrolled women had
      above average risk. Screening sensitivity in both arms was high. A benefit of
      mammography screening is supported by our modeling of the CNBSS-2 results.

PMID- 15146567
TI  - Maternal breast cancer risk after the death of a child.
AB  - The possible association between a severe traumatic life event (death of a child)
      and breast cancer risk was examined in a case-control study nested within a
      nation-wide cohort in Sweden. Our study population included 27,571 women with
      breast cancer and 141,798 control women born between 1925-1976. After adjustment
      for age, parity, age at first birth and education, the overall risk estimate for
      breast cancer among all women that had experienced the death of a child was 1.05
      (95% confidence interval [CI] = 0.96-1.15). Among uniparous women the
      corresponding odds ratio (OR) was 1.27 (95% CI = 0.98-1.64). When stratifying for
      child's age at death a significant risk increase was detected among women that
      had lost their only child when the child was between 1-4 years of age (OR = 2.65;
      95% CI = 1.06-6.60). These findings do not support an overall increase in breast
      cancer risk after the death of a child, a severe traumatic life event. Based on a
      small number of subjects, our finding of an increased risk in a subgroup of
      uniparous women losing their only child could be due to chance.

PMID- 15146568
TI  - In vivo administration of liposomal vincristine sensitizes drug-resistant human
      solid tumors.
AB  - Here we evaluated the antitumor efficacy of vincristine (VCR) encapsulated in
      sphingomyelin/cholesterol liposomes (SM/Chol) on drug-resistant human solid
      tumors. We firstly used the M14 human melanoma line and the counterpart resistant
      derivative, M14/R. The M14/R, selected after doxorubicin exposure, was cross
      resistant to VCR: the in vitro treatment with free VCR reduced the survival of
      M14, while M14/R line was completely resistant to VCR. Encapsulation in liposomes
      improved the efficacy of VCR in M14 cells and sensitized the M14/R line to the
      drug. Experiments in vivo confirmed these results. The treatment of M14 bearing
      mice with VCR resulted in marked reduction of tumor growth, while no antitumoral
      effect was observed in M14/R tumors. The administration of VCR encapsulated in
      liposomes was able to sensitize M14/R tumors to the drug, the antitumoral effect
      being comparable to that observed in M14 tumors after the same treatment. By
      injecting animals with the same dose of liposomal VCR fractionated into 3 daily
      injections and administering repeated cycles of treatment, to a marked
      improvement of the antitumor activity of liposomal VCR was observed. TUNEL assay
      in tumor sections indicated that the improved efficacy of liposomal VCR was
      related to the induction of massive necrosis and apoptosis. To confirm the
      efficacy of liposomal VCR on drug-resistant tumors, MCF7 breast and LoVo colon
      carcinomas, sensitive and resistant to VCR treatment, were also employed. The
      results showed that the treatment with liposomal VCR of mice bearing breast or
      colon resistant tumors reduced the tumor mass and delayed the tumor regrowth to
      the same extent observed in the sensitive counterpart. Together, these results
      demonstrate the ability of VCR encapsulated in liposomes in sensitizing drug
      resistant tumors of different histotypes.

PMID- 15146569
TI  - Association between war and cervical cancer among Vietnamese women.
AB  - Decades ago, cervical cancer was the leading form of cancer among women in both
      North Vietnam and South Vietnam. Currently, cervical cancer rates are
      considerably lower in the northern region of the country. We performed a case
      control study to measure factors associated with the development of cervical
      cancer among Vietnamese women. Questionnaire-based interviews were conducted with
      202 women in southern Vietnam and 97 women in northern Vietnam. Case subjects
      were women hospitalized with cervical cancer. Control subjects were women
      hospitalized with extrauterine neoplasms. Data were analyzed using logistic
      regression, and odds ratios for the development of invasive cervical cancer were
      measured. The development of invasive cervical cancer was significantly
      associated with military service by husbands during the Second Indochinese War
      and with parity status. Odds ratio for the development of cervical cancer among
      southern Vietnamese women whose husbands had served in the armed forces was 2.6
      (95% CI = 1.2-5.5). Odds ratio for the development of cervical cancer among
      northern women whose husbands had served in the armed forces was 3.9 (95% CI =
      1.5-10.4) if their husbands had been stationed in South Vietnam during the war
      years. Northern women whose husbands had served in the military experienced no
      significant increase in cervical cancer risk if their husbands had been stationed
      in North Vietnam during the war years. Geographic and temporal variation in
      cervical cancer rates among Vietnamese women was associated with the movement of
      soldiers. These findings may be useful for cervical cancer prevention efforts in
      Vietnam and in other countries.

PMID- 15146570
TI  - SV40 and human cancers.

PMID- 15146573
TI  - Changing the priority for HLA matching in kidney transplantation.

PMID- 15146574
TI  - Changing the priority for HLA matching in kidney transplantation.

PMID- 15146575
TI  - "Me-too" products--friend or foe?

PMID- 15146576
TI  - Acute chemical emergencies.

PMID- 15146577
TI  - AIDS fund announced.

PMID- 15146578
TI  - [Adult immunization].
AB  - Adults receive several vaccinations related to occupational health. Travellers or
      immunocompromised people who are exposed to infections need some other
      vaccinations, too. People older than 65 receive influenza vaccine every year.
      Tetanus and poliomyelitis immunity should be maintained with a decennial
      injection following adult immunisation schedule but the application of this
      vaccine remains rather erratic. Diphtheria valence included in a recently
      licensed combined vaccine could be done together. Maintenance of immunity against
      "childhood infectious diseases" preventable with vaccinations is a new challenge;
      measles, rubella and pertussis occur now quite often in adults: the risk of
      complications is higher in these ages. Adults may even become the source of the
      contamination of youngers: many infants affected with whooping cough have
      contracted the disease from their own parents. The immunisation against these
      diseases should be prosecuted in adults. Related with the development of more
      efficacious new vaccines, the indications of pneumococcus, meningococcus or
      varicella vaccines should be defined in some populations of adults. Immunization
      policy of adults should be revised in order to continue the vaccination program
      of childhood. Some infections that may affect adults should be prevented by
      improving vaccine application. A real adult immunisation schedule and
      recommendations for populations at risk of preventable infections should be set
      up and their application reinforced.

PMID- 15146579
TI  - [New pneumococcal vaccine].
AB  - Streptococcus Pneumoniae is the main pathogen bacteria responsible for invasive
      diseases (bacteremia, meningitis) in children less than 2 years of age. The new
      conjugate heptavalent pneumococcal vaccine (7 polysaccharide serotypes 4, 6B, 9V,
      14, 18C, 19F, 23F conjugated with the CRP 197 protein derived from diphteria
      anatoxin) is a great advance. This vaccine is well tolerated, immunogenic and
      efficient in infant. His efficacy in invasive pneumococcal diseases is more than
      95%. The reduction of pneumonia (with 2.5 cm X-Ray opacity) was 32.2% in the
      first year of age and 23.4% in the two first years in the vaccinated group. The
      efficacy in acute otitis media is poor French indications of this vaccine,
      limited to infants under 2 years of age with further risk factor, might be
      extended to all the infants under 2 years of age.

PMID- 15146580
TI  - [Pharmacovigilance of hepatitis B vaccines].
AB  - Since the hepatitis B vaccine are on the market in France, until the end of 2002,
      1211 observations of demyelinating disease of the central nervous system (1109
      cases of which 895 multiple sclerosis) or peripheral (102 cases of which 49
      Guillain Barre Syndrome), have been reported to the french network of
      pharmacovigilance and to the AFSSAPS. It is not possible to singularize these
      observations, neither from a clinical nor an epidemiological point of view. No
      risk factor has been detected. Only the chronology could suggest a causal
      relationship, the vaccine preceding the pathology in all the cases notified.

PMID- 15146581
TI  - [Mercury in vaccines].
AB  - Thiomersal, also called thimerosal, is an ethyl mercury derivative used as a
      preservative to prevent bacterial contamination of multidose vaccine vials after
      they have been opened. Exposure to low doses of thiomersal has essentially been
      associated with hypersensitivity reactions. Nevertheless there is no evidence
      that allergy to thiomersal could be induced by thiomersal-containing vaccines.
      Allergy to thiomersal is usually of delayed-hypersensitivity type, but its
      detection through cutaneous tests is not very reliable. Hypersensitivity to
      thiomersal is not considered as a contraindication to the use of thiomersal
      containing vaccines. In 1999 in the USA, thiomersal was present in approximately
      30 different childhood vaccines, whereas there were only 2 in France. Although
      there were no evidence of neurological toxicity in infants related to the use of
      thiomersal-containing vaccines, the FDA considered that the cumulative dose of
      mercury received by young infants following vaccination was high enough (although
      lower than the FDA threshold for methyl mercury) to request vaccine manufacturers
      to remove thiomersal from vaccine formulations. Since 2002, all childhood
      vaccines used in Europe and the USA are thiomersal-free or contain only minute
      amounts of thiomersal. Recently published studies have shown that the mercury
      levels in the blood, faeces and urine of children who had received thiomersal
      containing vaccines were much lower than those accepted by the American
      Environmental Protection Agency. It has also been demonstrated that the
      elimination of mercury in children was much faster than what was expected on the
      basis of studies conducted with methyl mercury originating from food. Recently,
      the hypothesis that mercury contained in vaccines could be the cause of autism
      and other neurological developmental disorders created a new debate in the
      medical community and the general public. To date, none of the epidemiological
      studies conducted in Europe and elsewhere support this assumption. Although any
      effort should be made to avoid useless exposure of vaccinees to a potentially
      toxic compound, it should be emphasized that 1) public communication on this
      issue has led to a decrease in the hepatitis B vaccination coverage of children
      born to HBs Ag positive mothers in the US; 2) this issue was not really relevant
      in France where until 2002, apart from two hepatitis B vaccines, all childhood
      vaccines were thiomersal-free, and 3) in developing countries using multidose
      vaccine vials, moving to thiomersal-free vaccines in unidose presentations would
      represent such an incremental cost that millions of children would no more have
      access to vaccination. Therefore the World Health Organisation still recommends
      the use of thiomersal-containing vaccines as part of the expanded programme of
      immunisation.

PMID- 15146583
TI  - [Genetics and physiopathology of primary or secondary pulmonary artery
      hypertension].
AB  - Primary or secondary pulmonary hypertension (PH) is an unexplained condition
      whose severe forms in adults or neonates are fatal and for which no satisfactory
      treatment is available. Considerable progress has been achieved over the last few
      years in our understanding of this disease, both through genetic studies that
      have identified mutations in the gene for BMP-RII (bone morphogenetic protein
      receptor II) in patients with familial primary PH (PPH) and through
      pathophysiological investigations that have elucidated the molecular mechanisms
      involved in hypertrophic arterial wall remodelling, most notably the role for the
      serotonin transporter (5-HTT) in hyperplasia of pulmonary artery smooth muscle
      cells (PA-SMCs). Identification of the BMP (bone morphogenetic protein) pathway
      as relevant to the aetiology of PPH now raises many questions about the link
      between the BMP-RII mutant genotype and the PPH phenotype. That PPH does not
      develop in all subjects with BMP-RII mutations suggests a crucial role for
      environmental or associated genetic factors. Simultaneously, mechanistic studies
      investigating the biological processes that underlie the complex vascular changes
      associated with PPH have identified major molecular pathways involved in
      constriction and proliferation of pulmonary vascular smooth muscle cells,
      dysfunction of endothelial cells, and remodelling of extracellular matrix. Such
      mechanisms may be involved either in initiating or in perpetuating the disease.
      The finding that genetic polymorphism of some of the candidate genes related to
      these processes is closely associated with PPH suggests a causal relationship
      between the expression, or function, of these genes and the PPH phenotype. The
      association between PPH and the L allelic variant of the serotonin transporter (5
      HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia,
      probably contributes to susceptibility to PPH or is an important modifier of the
      PPH phenotype. Recognition of these molecular pathways should provide insight
      into the pathogenesis not only of primary PH, but also of secondary forms of PH.
      This should lead soon to the development of new and more selective therapeutic
      approaches to pulmonary hypertension.

PMID- 15146582
TI  - [Vaccine adjuvants and macrophagic myofasciitis].
AB  - Aluminium-based adjuvants have been used throughout the world since 1926, and
      their safety profile is such that they have long been the sole adjuvants
      registered for clinical use. Their safety has nevertheless been questioned in
      France over the last few years following the demonstration that aluminium could
      persist for prolonged periods at the injection site, within macrophages gathered
      around the muscular fibers and forming a microscopic histological lesion called
      "macrophagic myofasciitis (MMF)". This image has been observed in patients
      undergoing a deltoid muscular biopsy for diagnostic purposes of various symptoms
      essentially including muscular pain and fatigue, in association with a large
      panel of various symptoms and diseases, including those of an autoimmune nature.
      Studies of the clinical, biological and epidemiological characteristics
      undertaken to identify a possible association between the MMF histological image
      and a systemic disease have remained negative. As of today, available evidence
      indicates that although vaccine aluminium may persist at the site of injection
      for years ("vaccine tattoo"), this does not reflect the existence of a diffuse
      inflammatory muscular disease and is not associated with a specific clinical
      disease. The existence of sampling bias inherent to the complexity of the
      clinical and pathological diagnoses remains the most likely hypothesis.

PMID- 15146584
TI  - [Primary hyperparathyroidism: three decades of evolution in diagnostic and
      imaging techniques and advantages of early surgery].
AB  - Recent progresses in the ability to obtain a secure diagnosis and preoperative
      localisation have resulted in a lower threshold for surgery of primary
      hyperparathyroidism. We questioned whether these trends have been accompanied by
      an improvement in surgical results, or changes in the profile of the disease
      among operated patients. From a total of 511 operations (499 patients), we
      retrospectively investigated the data from three successive periods of 10 years
      each: (1973-1982: 73 operations; (1983-1992): 155 operations; (1993-2002): 283
      operations. Rates of surgical failure, defined as persistent hypercalcaemia at
      six months, have progressively declined: 6.8%, 1.3% and 0.7% respectively. There
      also has been a decline in the rates of permanent hypoparathyroidism or laryngeal
      nerve injury. However, these complications were highly influenced by the
      underlying pathology (surgery for single adenoma versus surgery for multiple
      gland disease) and by the need for concomitant thyroid surgery. Considering signs
      and symptoms, the frequency of kidney stones has declined from 50% to 29.7%,
      while the rate of patients diagnosed at routine screening has increased from 19%
      to 39%. The prevalence of parathyroid cancer among operated patients has
      successively declined from 6.8% to 1.3%, then 0% during the last period. Our data
      suggest that present improvement in the success rate of parathyroid surgery be
      partly due to improvement in preoperative localisation. Among imaging techniques,
      subtraction scintigraphy, based on the simultaneous recording of technetium-99m
      sestamibi and iodine-123, provided the highest rate of accurate location (92.6%).
      Because this imaging technique depicted a majority of cases of multiple
      parathyroid gland disease at prospective evaluation (14 out of 15), we now use it
      to select appropriate cases for a focussed surgery under local anaesthesia,
      without the additional need for intraoperative PTH monitoring. The present good
      surgical results would justify surgery even for elderly or asymptomatic patients.
      Surgery carried out before appearance of symptoms seems beneficial. Only
      asymptomatic patients with a short life expectancy may be denied surgery.

PMID- 15146585
TI  - [Obstetrics in crisis].
AB  - Obstetrical practice in France is in a crisis with several components. The number
      of obstetricians is in sharp reduction, a litigation crisis is obvious, an
      important number of for profit maternity units disappeared since five years for
      financial reasons. To rebuild an adapted system, one should be aware of the wills
      of obstetricians in training about the minimal number of members of any
      obstetrical team to share the on call duty (7 to 8). It will be difficult to
      resolve the litigation crisis, some tools are available such as quality audits
      systems among professionals (quality circles), and those professional groups
      could induce a renewed relationship with the insurers trough group contracts.

PMID- 15146586
TI  - [Prenatal diagnosis: uncertainties and perspectives].
AB  - The practice of faetal medicine has been regulated by law as of July 29th 1994,
      licensing Multidisciplinary Centres for Prenatal Diagnosis. With time passing by,
      echography has become more and more accurate, genetics and molecular biology
      further developed, prenatal diagnosis increasingly precocious and intrusive.
      Indications for medical interruption of pregnancy are easy to decide for obvious
      malformations. They become far more difficult when they concern a risk of disease
      or handicap often hazardous to quantify. Beneficial for the sake of individuals,
      prenatal diagnosis may happen to possibly appear collectively detrimental, as for
      the systematic screening for Down syndrome. Testing of faetal DNA, present in
      maternal serum since the early weeks of pregnancy, should in the near future
      outset antenatal invasive procedures and provide a useful alternative to pre
      implantation diagnosis.

PMID- 15146587
TI  - [Access to personal origins: the new French law].
AB  - The French parliament adopted in January 2002 a law on access to the origins of
      persons who where adopted at birth. The National Council for access to personal
      origins (CNAOP) was created in order to apply this new law. The law's purpose was
      to attempt to conciliate the interests of adults who wish to know their origins,
      those of pregnant women who want to keep their motherhood secret, and those of
      children who have the right to live in the best conditions, and obtain the best
      possible chance of having a happy childhood. In short, the legislator attempted
      to find a balance between situations of extreme suffering. The new law does not
      impose on the natural mother to communicate her identity, even confidentially. A
      woman who requests, at the time of delivery, that her admission and her identity
      be kept secret, is encouraged to leave, on a voluntary basis, information on her
      health and that of the father, the origins of the child and the circumstances of
      birth, as well as her identity, in a sealed envelope. In this sealed envelope,
      she can specify her name, her date and place of birth. On the cover of the
      envelope are written the first names that she may have chosen for the child, as
      well as its sex, date, hour and place of birth. This envelope is stored and can
      be unsealed only by a member of the CNAOP if this organism is solicited by the
      child when reaching adulthood, or if the child is minor, by his legal
      representatives or by himself with these representatives' approval. In this case,
      CNAOP can search for the mother and contact her. She may maintain or waive the
      secret of her motherhood. Furthermore, the natural mother can at any time waive
      the secret of her identity, in the event that the child solicits the CNAOP, but
      she does not have the right to search for the child. It will take several years
      to determine whether the effects of these new dispositions are beneficial or not.
      One of the keys to this problem is improved management of these women in the
      departments of obstetrics and gynecology.

PMID- 15146588
TI  - [Miguel Servet, 450 years ago].
AB  - Miguel Servet, Spanish, who studied, practiced and lectured Medicine in France,
      was burnt in effigy by the Catholics at Vienne in the French Dauphine on June
      17th, 1553, and in person at John Calvin's instigation in Geneva, on October
      27th, 1553. Miguel Servet's works were also burned with him.

PMID- 15146589
TI  - New bedfellows. Baylor medical school switches hospital partners.

PMID- 15146590
TI  - Too much too soon? JCAHO's proposed 2007 deadline for bedside bar-code technology
      has some providers scurrying, but vendors call the plan doable.
AB  - The JCAHO is proposing mandatory bar-code technology at bedside by 2007. Michael
      Cohen, left, of the Institute of Safe Medication Practices, says the deadline may
      be too soon. Others say it could be met and are starting to train staff members
      on the equipment. In the cover photo, workers at Vanderbilt University Medical
      Center learn how to operate infusion pumps that double-check dosages.

PMID- 15146591
TI  - Fighting back. Specialty hospital group campaigns against ban.

PMID- 15146592
TI  - MedPAC rejects freeze on LTACs.

PMID- 15146593
TI  - Virtual moves. 121 hospitals approved for wage reclassification.

PMID- 15146594
TI  - Screen test. HCA tries to move nonemergency patients out of ER.

PMID- 15146595
TI  - Learning the rules. Docs, others prepare for drug card questions.

PMID- 15146596
TI  - Flunking out. Three quit in fallout at Maryland General Hospital.

PMID- 15146597
TI  - Eyeing transparency. To hospitals' dismay, Calif. bill seeks more disclosure.

PMID- 15146598
TI  - Beyond safety. Patient trust and loyalty are byproducts of patients' overall
      experience.

PMID- 15146599
TI  - Ready. Or not. Talented, high-achieving physicians often come up short in the
      skills and other attributes needed to excel as CEO.

PMID- 15146600
TI  - Debugging hospitals. Technology helps track hospital-acquired infections, along
      with the often unreimbursed costs of treating them.

PMID- 15146601
TI  - [Physiology of somatotropic axis: interest of gene inactivation experiments].
AB  - Research into the somatotropic axis (growth hormone, insulin-like growth factors)
      has received renewed attention in the last few years, owing to techniques for
      genetic modification in the mouse, essentially transgenesis, and gene
      inactivation. The results, compared with phenotypic and molecular data for
      various pathological conditions, e.g. short stature, have increased our
      understanding of the function of the various parameters of the somatotropic axis,
      especially those of the insulin-like growth factor (IGF) system. During fetal
      development, IGF-II (which is subject to imprinting) and IGF-I are essential for
      increases in height and weight and for development of the various organs, adipose
      tissue in particular. The action of these two IGF is mediated by the IGF type 1
      receptor. Total inactivation of the IGF-I gene, the paternal allele of the IGF-II
      gene or the IGF type 1 receptor gene leads to growth retardation resulting in
      mouse fetuses weighing only 60%, 60% and 45% of their wild-type controls.
      Combinations of these inactivations have shown that IGF-II also exerts its
      effects by interacting with another, as yet uncharacterized receptor. Moreover,
      inactivation of the IGF-I gene specifically in the liver, organ which normally
      maintains the high IGF-I concentrations in the blood (endocrine action), has no
      effect on growth, demonstrating that local IGF-I plays an auto/paracrine role in
      the periphery, under the direct influence of growth hormone (GH). However,
      endocrine IGF-I plays an important role in metabolism and cellular proliferation,
      and its function in mitosis may favor the development of cancer in the breast,
      colon and prostate. Mice with homozygous inactivation of the IGF type 1 receptor
      gene are not viable after birth. Partial and conditional inactivation have made
      it possible to study the physiology of these factors in adult animals. In
      contrast to IGF-II, the IGF type 1 receptor is, like IGF-I, involved in postnatal
      growth regulation. Lack of IGF type 1 receptor or of IGF-I affects both height
      and weight, and shows that this receptor is particularly involved in promoting
      pubertal growth. The activated receptor acts differently and specifically in each
      tissue. Finally, the IGF type 1 receptor has recently been implicated in the
      control of lifespan: a 50% decrease in the number of receptors increased the
      lifespan of these mice by 26%. This increase displayed sexual dimorphism, being
      greater for females (33%) than for males (16%). Invalidations combining different
      properties--specificities according to tissue, development stage or inducibility
      by an exogenous product--will facilitate fine dissection of the roles of the
      various ubiquitous actors in the IGF system.

PMID- 15146602
TI  - [Diagnostic and therapeutic strategies in Zollinger-Ellison syndrome associated
      with multiple endocrine neoplasia type I (MEN-I): experience of the Zollinger
      Ellison Syndrome Research Group: Bichat 1958-1999].
AB  - About 25% of patients with ZES have MEN 1. Except diarrhoea, less frequent in
      patients with ZES-MEN 1 than in sporadic ZES, and specific MEN 1-related signs,
      clinical characteristics are similar in both ZES types. Acid output and gastrin
      levels are also similar whether in the basal state or after secretin stimulation.
      Primary hyperparathyroidism (PHPT) exists in the majority of ZES-MEN 1 patients,
      30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25
      to 30% have EC-Lomas; bronchial and thymic carcinoids have probably been
      underevaluated. Gastrinomas are multiple predominantly located in the duodenal
      wall, but also in the pancreas in association with clinically silent endocrine
      tumors. The spread of the disease: metastases to the liver (LM), mediastinum,
      bones, is evaluated at best by Octreoscan. Endoscopic ultrasonography evaluates
      the number, size and anatomical characteristics of gastrinomas. Patients without
      LM have an excellent prognosis. Surgery never cures ZES, but is necessary in case
      of associated life-threatening condition such as insulinoma and has been
      advocated to prevent LM development in patients with large pancreatic tumor(s).
      However although, indeed, the size of the tumor, when located in the pancreas > 3
      cm, favours metachronous LM occurrence, surgery, in our experience, has not been
      able to prevent LM development. Hepatic malignancies remain however the most
      pejorative prognostic determinant for survival and raise the most difficult
      therapeutic challenge. Surgery is the best option whenever feasible; specific
      chemotherapy and chemo-embolisation have not conclusively achieved definite
      successes. Long-term octreotide treatment, however, has been shown recently to
      obtain tumour stabilisation. Internal irradiation with 90 Ytrium-labelled
      octreotide is a new promising option, presently under evaluation (Novartis
      European trial). Preliminary results are promising.

PMID- 15146603
TI  - [Molecular mechanisms of bile formation and cholestatic diseases].
AB  - Biliary function is a vital function of the liver which results from the
      vectorial transport of endogenous and exogenous substrates through three
      compartments sequentially: the vascular space, the cellular space and the biliary
      space. The biliary function is responsible for the homeostasis of lipid
      metabolism in particular of cholesterol metabolism, the elimination of toxic endo
      -and xenobiotics such as (bilirubin, lipid bacteria products (endotoxin)) and
      several inflammatory mediators. Bile elaborated in canaliculi, is modified by
      cholangiocytes through secretion and absorption. Bile is essential for the
      intestinal digestion and absorption of nutriments. The main determinant of bile
      formation is an osmotic filtration process resulting from active transport of
      bile acids and other osmotic solutes (glutathione). Most of the membrane
      transporters ensuring bile formation have now been identified. The expression of
      these membrane transporters is regulated through transcriptional and post
      tranductional mechanisms. Transcriptional regulation is under the control of
      nuclear receptors activated by ligands such as bile acids, which act as
      endogenous steroids synthesized from cholesterol in hepatocytes. Cholestatic
      liver diseases comprise genetic diseases resulting from the complex interaction
      between genetic and environmental factors. Monogenic cholestatic diseases
      recently identified illustrate the key role of membrane transporters in biliary
      function. Bile acids and inflammatory mediators are potent modulators
      transporters and nuclear receptor genes and thus trigger an adaptative response
      to cholestasis. The extent of this adaptative response could explain the
      compelling phenotypic variability of cholestatic diseases in childhood and
      adults. The firstline medical treatment is currently ursodeoxycholic acid and in
      case of failure of this medical treatment, liver transplantation is required.
      Recent progress in the molecular pathogenesis of bile formation and cholestatic
      liver diseases is expected to provide the design of drugs targeted to the
      molecular abnormalities typical of cholestatic diseases.

PMID- 15146604
TI  - [Treatment of insulin-dependent diabetes: new therapy by electromagnetic
      replacement: towards an artificial pancreas].
AB  - The goal of treatment of diabetes mellitus is the achievement of sustained
      normoglycemia to prevent the complications with the lowest incidence of
      hypoglycemia. In the same time, it attempts to reduce the hourly and daily
      constraints due to multiple injections and self monitoring of glycemia. Both
      intermittent injections and subcutaneous route are inappropriated to extreme
      precision and flexibility of regulation requested to reach optimal glycemic
      control and the best quality of life in most diabetic people. The progress in
      biomaterials and micro-electronics, the availability of stable insulin solutions
      have permitted to implant a pump with an awaited functional autonomy for 10 years
      and to perfuse insulin by peritoneal way in a continuous and modulable fashion.
      The intra-vascular implanted enzymatic glucose sensors, using glucose-oxidase,
      are able to measure with good accuracy real-time blood glucose for the duration
      from 6 to 12 months. The combination of these two linked devices implanted in
      type 1 diabetic patients has given the opportunity to perform the first trials
      for periods of 48 hours delivering automated insulin according to glycemic
      variability. This most physiological restoration of insulin function is feasible
      and appears to represent a possibility for long term treatment of diabetics.

PMID- 15146605
TI  - [Treatment of insulin-dependent diabetes: new therapeutics. Cellular replacement:
      facts and perspectives].
AB  - The replacement of insulin producing beta cells by islet transplantation can
      effectively control blood glucose levels in individuals with Type I diabetes.
      Recent improvements in clinical results were made possible by transplantation of
      greater islet masses and introduction of new immunosuppressive protocols, which
      avoid diabetogenicity. Future, widespread clinical application of islet
      transplantation will depend on the availability of an unlimited source of glucose
      sensitive, insulin-secreting tissue and less toxic immunosuppressors.

PMID- 15146606
TI  - [Non-insulin-dependent diabetes: an expanding disease. Importance of a
      multidisciplinary approach].
AB  - Non-insulinodependent diabetes mellitus (NIDDM) or Type 2 diabetes mellitus
      concerns in 2003 more than 185 million people in the world, a number likely to
      double by 2025. Occurring in genetically predisposed individuals, NIDDM is
      favoured by excessive body weight and sedentarity. Individuals affected by NIDDM
      have a high risk of cardio-vascular disease, their management requires a
      multifactorial approach. Lifestyle changes are efficient in preventing, or at
      least delaying, NIDDM. In concerted action with the World Health Organisation,
      the International Diabetes Federation has launched an awareness campaign to
      sensitize governments and health authorities to the current diabetes epidemics.

PMID- 15146608
TI  - [Natural history of obesity].
AB  - Obesity is a chronic disease. At the initial phase, behavioral and environmental
      factors play a key role in the constitution of adipose tissue excess.
      Progressively biological alterations of adipose tissue metabolism lead to some
      degree of irreversibility of the disease and contribute to the development of its
      metabolic and cardio-vascular complications.

PMID- 15146607
TI  - [Non-insulin-dependent diabetes: an expanding disease. Diabetic ophthalmopathy:
      diabetic retinopathy facts].
AB  - Diabetic retinopathy (DR) is the 5th cause of blindness in the population of less
      than 50 years old in industrialized countries. Sample survey showed a lack of
      detection of DR and a discrepancy between the medical practices and the
      guidelines during the follow-up. Moreover the number of ophthalmologists is
      decreasing and the number of diabetics increasing. Faced with this public health
      problem, an organization for detecting the DR is in progress: non mydriatic
      digital camera are used by non medical technicians connected with reading
      centres. Diabetic macular edema (DME) is the most common cause of visual
      impairment. Recently, optical coherence tomography (OCT), a new imaging tool has
      showed the role of vitreous tractions in some DME. OCT provides clear diagnostic
      elements for vitrectomy indications. Very recently, vitrectomy proved to be
      favorable in DME with vitreous tractions.

PMID- 15146609
TI  - [Adipose tissue: new aspects].
AB  - During the last past years, obesity had become a major public health problem, and
      new aspects of fat cells biology have been unraveled. First, since the discovery
      of leptin, the adipocytes has been recognized as true endocrine cells secreting a
      variety of factors in a regulated manner. The role of these factors on the
      development of obesity-associated metabolic complications is becoming
      increasingly clear. Also, the process of fat cell differentiation has been
      uncovered, leading to the possibility of efficient targeting protein expression
      in adipose tissue. Finally, lines of transgenic mice have been created, some of
      which are totally resistant to obesity. These models led to the identification of
      new potential adipose targets for the treatment of obesity.

PMID- 15146611
TI  - [Observations on eating].
AB  - How the epidemic obesity appeared in the United States during the eighties.
      Respective intake of fats, proteins and saccharides in the diet is notified.
      Sugars such as sucrose provide pleasure and reward specially by infants and
      children. Lactose occurs in the life of the newborn with a peculiar situation;
      its sweetening effect is weak and devoid of any neurochemical stimulation. The
      amounts of lipids and sugars in the daily diet are frequently excessive if
      physical activity is inappropriate. TV dinners are specially endangered. Eating
      too much snacks disrupts the physiological rhythm of the digestive economy. The
      carbonated soft beverages' are used instead of water, affording large amounts of
      inapparent sugars. Ice creams are often too rich in sugars and lipids. Fruits and
      vegetable fibers fail in the diet.

PMID- 15146610
TI  - [Physiological and neurobiological aspects of eating].
AB  - Many methods and technics have accumulated a considerable mass of data about the
      mechanisms which control food intake and energetic loss. After a presentation of
      the most relevant signals sent by peripheral organs to the central nervous
      system: Glucose, triglycerides; from adipocytes: Leptin; from pancreas: Insulin,
      pancreatic polypeptide, amylin, enterostatin; from digestive tract: Ghrelin,
      cholecystokinin, peptide Y Y 3-36 we consider, especially at the hypothalamic
      level, their interpretation by neurones whose transmitters are either
      neuropeptides such as: Neuropeptide Y, Agouti Related Peptide,
      Cocaine/Amphetamine Regulated Transcript, Melanin Concentrating Hormone, alpha
      Melanocyte Stimulating Hormone, orexins/hypocretins, octadecaneuropeptide,
      nociceptin/orphanin FQ, opioid peptides, Interleukin 1, galanin, urocortin 2,
      Neurotrophic ciliary factor, Glutamate, or monoamines such as: Dopamine,
      Norepinephrin, serotonin, GABA, histamine, acetylcholine. After this brief
      synopsis one should not be surprised that this so complex system which regulates
      feeding may be affected by various disorders; however one may be amazed by such a
      scarcity of drugs to influence it; whatever may be it predicts many new
      pharmacological strategies in this respect.

PMID- 15146613
TI  - Middle East. Another kind of warrior.

PMID- 15146612
TI  - [Edmond Nocard, a forerunner in microbiology, comparative pathology and public
      health].

PMID- 15146614
TI  - Why don't we call them quirky?

PMID- 15146615
TI  - The titans of trivia.

PMID- 15146616
TI  - Easing the drug crunch.

PMID- 15146617
TI  - Patch up that scar.

PMID- 15146618
TI  - [Structure and dynamics of Taxus chinensis var. mairei clonal population].
AB  - Structure and dynamics of Taxus chinensis var. mairei clonal population were
      studied. The results showed that according to the life history of Taxus chinensis
      var. mairei, the modular population could be divided into 6 classes. The
      development of Taxus chinensis var. mairei population was greatly depended on its
      ramets, which sprouted on its stem, and the population size structure was stable.
      The survival curve of Taxus chinensis var. mairei population showed a revered 'J'
      type. To expanding and continuing the population, there were high ramet sprouting
      rate and the resource limit induced a higher seedling and sapling mortality rate.
      When sapling grew up as young tree, its adventitious root stretched into soil to
      assimilate the nutrient and water, and it became independence individual. Before
      germination, the seed of Taxus need to dormant for more than one year, and the
      bird and beast liked to eat the seed, so it was hard to find seedling and sapling
      from seed. Therefore Taxus chinesis var. mairei had been considered to be a
      decline or none descendant population. In this study, it was found that Taxus
      chinensis var. mairei had a powerful asexual multiplication in Yuanbaoshan,
      especially ramet sprouting on stem. It was depend on this way to develop and
      expand the population.

PMID- 15146619
TI  - [Influence of shelterbelts structure on snow distribution pattern in shelternets
      in Northeast China].
AB  - The amount of snow that falls in farmland during winter in Northeast China is the
      important source of soil water in farmland, so the influence of shelterbelt
      structure on snow distribution pattern is the key problem in order to adjust
      structure of shelterbelts according to porosity in management practice. Based on
      snow depths in shelternets composed of shelterbelts with three levels of
      porosity, which were shelternet No. 1, shelternet No. 2, and shelternet No. 3,
      the snow distribution patterns in farmland were studied. The results showed that
      the structure of shelternet had great influence on snow distribution in farmland.
      With different levels of porosities, spatial pattern of snow distribution were
      obviously different in three shelternets. The more variant in porosity, the more
      obvious difference in snow distribution pattern, and the best uniformity of snow
      distribution appeared in shelternet with porosity of phi 2w = 0.579, phi 2s =
      0.268, in which snow depth in farmland was relative even and the variability of
      snow depth was the least. Consequently, the relationship of porosity of
      shelterbelt with snow distribution pattern could be used to guide structure
      adjustment and optimization management of shelterbelts.

PMID- 15146620
TI  - [Diversity of Frankia in nodules of Alnus nepalensis at Gaoligong Mountains
      revealed by IGS, PCR-RFLP analysis].
AB  - 30 nodule samples were used to assess the diversity of Frankia strains
      symbiotically associated with Alnus nepalensis naturally occurring at the
      Gaoligong Mountains in Yunnan Province, China. DNA was extracted directly from
      nodules, and its two target DNA regions that encode nifD-nifK intergenic spacer
      (IGS) and 16S-23S rDNA IGS was studied by PCR-RFLP. The PCR fragments yielded by
      the nifD-nifK IGS were noticeably different in size, and when they were digested
      by Hae III and Afa I, 15 nif-type Frankia strains could be detected, the PCR-RFLP
      result of this region also could show that more than one genotype Frankia strains
      could form symbiosis with individual plants at the same time. The 16S-23S rDNA
      IGS had similar PCR fragments, but still identified 15 rrn-type strains after
      digested by Hae III and Afa I. 20 genotype strains could be found only when
      combined the PCR-RFLPs of two target regions.

PMID- 15146621
TI  - [Effects of gap in primitive subalpine fir forest on diversity of herb and shrub
      in Tibet].
AB  - Effects of gap in primitive fir forest in southeast Tibet on species diversity of
      herb and shrub were studied. The results showed that species composition,
      distribution and diversity in gap were different from those in non-gap. The
      improvement of illumination and other habitat conditions resulted in richer
      species of herb and shrub in gap. There were shade-tolerant and photophilic herb
      species and shrub species in gap, however, only shade-tolerant herb species and
      shrub species grew in non-gap. Species diversity and evenness in gap were higher
      than in non-gap. The diminutive similar coefficient between herb and shrub
      communities showed that certain difference existed between herb and shrub
      communities in stands of gap and non-gap. The similar coefficients were little
      correlative between gap area and communities. Gap was important to improve growth
      of herb and shrub and maintain species diversity of primitive subalpine fir
      forest in southwest Tibet.

PMID- 15146622
TI  - [Relationships between water and productivity of seabuckthorn (Hippophae) in
      different habitats of the Loess Plateau, China].
AB  - This paper deals with the relationships between water and productivity of
      seabuckthorn in different habitats of the Loess Plateau in north Shaanxi. The
      typical habitats were classified with hilltop, sunny, shady, semi-shady and semi
      sunny hillside. The results showed that values of transpiration of five kinds of
      habitats were different, and transpiration of semi-shady was relatively stronger
      in the morning while others were weaker. With the variation of directions of
      sunshine, transpiration of shady and sunny was declining and meanwhile
      transpiration of hill-top was steady. transpiration of semi-shady reached the
      peak in 12:00. In the afternoon, these values of transpiration all reduced in
      different extents except seabuckthorn of shady, especially semi-shady. The mean
      transpiration of 5 habitats was ordered in semi-shade > shade > semi-sunny >
      hilltop > sunny. There were remarkable difference between diffuse resistance and
      transpiration, and same relationship was found between relative humidity and
      transpiration. But this relationship was not found between light intensity and
      transpiration. Different habitats had different productivities, and productivity
      of seabuckthorn in shade habitat was higher than those in other habitats.

PMID- 15146623
TI  - [Response of stomatal characteristics and its plasticity to different light
      intensities in leaves of seven tropical woody seedlings].
AB  - Stomatal characteristics and its plasticity in leaves of four canopy species,
      Shorea chinensis, Pometia tomentosa, Anthocephalus chinensis, Calophyllun
      polyanthum and three middle-layer species, Barringtonia pendula, Garcinia
      hanburyi, Horsfieldia tetratepala acclimated to different light conditions (8%,
      25%, 50% and 100% of full sunlight) for more than one year were surveyed. All
      plant's stomata were distributed on the abaxial of leaves. Pometia tomentosa and
      Barringtonia pendula had higher stomatal density, and the guard cell length of
      Anthocephalus chinensis and Calophyllun polyanthum were much greater than
      others'. Stomatal density and stomatal index (ratio of stomatal numbers to
      epidermal cell number) were increased with growth irradiance increased, while
      numbers of stomata per leaf were higher in the low than the high relative PFD,
      and stomatal conductance of leaves was the highest in the 50% of sunlight except
      for Anthocephalus chinensis. The relative PFD had little effects on the guard
      cell length of all seven plants. There was a significant negative correlation
      between stomatal density and leaf area, but the stomatal conductance was not
      significantly positive with the stomatal conductance in some degree. The analysis
      of phenotypic plasticity of stomatal characteristics showed that plasticity index
      for stomatal index and numbers of stomatal per leaf were similar for canopy and
      middle-layer species, while the plasticity index of stomatal density and stomatal
      conductance were significantly greater for canopy species than middle-layer
      species. The high plasticity of canopy species was consistent with the hypothesis
      that specialization in a more favorable environment increases plasticity.

PMID- 15146624
TI  - [Comparative study on daily change of photosynthesis rate of the rhizomatous
      grasses in milky ripe stage].
AB  - Comparative study on daily change of photosynthesis rate of the rhizomatous
      grasses in their milky ripe stage was carried out, and the results showed that
      photosynthetic rate of five grasses appeared to be two-apex curve, except
      Elytrigia intermedia appeared to be one-apex curve. The general trend was that
      the higher the root/shoot ratio was, the later the first apex of the
      photosynthetic rate reached, and the shorter the noon break period was. Moreover,
      low relative humidity and high leaf temperature were the important factors for
      noon break. Leymus chinense, Pascopyrum smithii Rydb. cn. Rosana, Leymus
      secalinus, Leymus racemosus, Agropyron mongolicum and Elytrigia intermedia
      reached the first apex at 10:12, 10:00, 9:51, 9:39, 9:06 and 8:13, the noon break
      period was 471, 474, 464, 467 and 551 min, and the average leaf temperature
      during noon break was 37.8, 37.5, 36.9, 37.0 and 36.3 degrees C, respectively.
      Leymus chinense and Agropyron mongolicum, Leymus secalinus and Leymus racemosus
      had similar daily change in photosynthetic rate, respectively, and their r values
      were 0.88 and 0.96 respectively when R = 0.01.

PMID- 15146625
TI  - [Simplification of crop shortage water index and its application in drought
      remote sensing monitoring].
AB  - Based on the principle of energy balance, the method for calculating latent
      evaporation was simplified, and hence, the construction of the drought remote
      sensing monitoring model of crop water shortage index was also simplified. Since
      the modified model involved fewer parameters and reduced computing times, it was
      more suitable for the operation running in the routine services. After collecting
      the concerned meteorological elements and the NOAA/AVHRR image data, the new
      model was applied to monitor the spring drought in Guanzhong, Shanxi Province.
      The results showed that the monitoring results from the new model, which also
      took more considerations of the effects of the ground coverage conditions and
      meteorological elements such as wind speed and the water pressure, were much
      better than the results from the model of vegetation water supply index. From the
      view of the computing times, service effects and monitoring results, the
      simplified crop water shortage index model was more suitable for practical use.
      In addition, the reasons of the abnormal results of CWSI > 1 in some regions in
      the case studies were also discussed in this paper.

PMID- 15146626
TI  - [Phosphorus translocation and distribution in intercropping systems of soybean
      (Glycine max) and citrus (Citrus poonensis)].
AB  - A field mini-plot experiment was conducted on clay loamy oxisol using 32P trace
      technique when P fertilizer was applied in three depth soil (15, 35 and 55 cm
      soil layer) to compare P absorption, distribution and translocation in plant
      organ and soil profile under soybean and citrus monoculture and intercropping at
      Taoyuan Experimental Station of Agroecosystem Research of Chinese Academy of
      Science. Total P uptake (PT) and P accumulation in different parts (PA) of
      soybean were remarkably decreased under intercropping. When 32P was applied in
      topsoil (15 cm soil layer), 32P uptake (32PT) by soybean was significantly lower
      in intercropping than in monoculture. Whereas 32PT uptake by soybean was
      significantly greater in intercropping than in monoculture when 32P was applied
      in deep soil layer (35 cm or 55 cm soil layer). However, considerable difference
      was not observed for 32P translocation and distribution among soybean organs.
      32PT uptake by citrus was much lower under intercropping than under monoculture.
      The P uptake by citrus newly could be transferred rapidly to aboveground and
      prior to active growing organ. Intercropping did not affect 32P distribution in
      citrus organ, but when P was applied in deep soil layer, the speed of 32P
      transferred to aboveground and active organ was slowed down. P mobility was
      strengthened in soil profile, and P of deep soil layer was promoted to move to
      topsoil in intercropping. The experimental results showed the optimal depth of
      applied P should be within 20 cm soil layer in soybean-citrus intercropping
      system.

PMID- 15146627
TI  - [Effects of peanut mixed cropping with different gramineous plants on apoplast
      iron accumulation and reducing capacity of peanut].
AB  - The effects of peanut mixed cropping with five different gramineous plants on
      apoplast iron accumulation and reducing capacity of peanut were investigated by
      soil culture experiment. The results showed that mixed cropping of maize, barley,
      oats, wheat, and sorghum with peanut could improve iron nutrition of peanut
      respectively. The phytosiderophores excretion rate of barley, oats and wheat were
      much higher than that of maize, and the phytosiderophores excretion rate of
      sorghum was lower than that of maize. In comparison with peanut in monocropping
      the iron content in different organs of peanut mixed with maize, barley, oats,
      wheat and sorghum were increased. The Fe content in root apoplast of peanut mixed
      with five different gramineous was gradually increased and higher than that of
      peanut in monocropping at different growth days. At the same time, the mixed
      cropping systems remarkably improved the soil Fe availability in the rhizosphere
      and root Fe reducing capacity of peanut. The higher root Fe (III) reducing
      capacity and much more available Fe in the rhizospe (III) of peanut in mixed
      cropping played an important role in improving iron nutrition of peanut.

PMID- 15146628
TI  - [Accumulation pattern of dry matter, nitrogen, phosphorus, potassium and silicon
      in rice genotypes and their relationships].
AB  - The accumulation of dry matter, nitrogen, phosphorus, potassium and silicon in 30
      rice genotypes and their relationships under field condition were studied. The
      results showed that dry matter accumulated at ripening stage linearly increased
      with increase of nitrogen, phosphorus, potassium and silicon accumulation with
      highly significant correlation coefficients at both early and late season. At the
      same time balance of nitrogen, phosphorus, potassium and silicon accumulation was
      beneficial for dry matter accumulation, which linearly increased with increase of
      nutrient balance index and decreased with increase of nutrient deviation index.
      The nitrogen, phosphorus, potassium and silicon were accumulated at the rate of
      3.76:1:4.55:7.10 at early season and 2.88:1:4.54:8.09 at late season. During
      growth period, dry matter accumulation was the highest at middle stage, then late
      stage and early stage. But nitrogen accumulation was the highest at early stage,
      then middle stage and late stage. The dry matter accumulated before heading was
      mainly distributed in stem and leaf sheath, with the highest ratio of stem and
      leaf sheath to total dry matter at heading stage. In contrast, nitrogen
      accumulated before heading was mainly distributed in leaf blade, and the ratio of
      nitrogen in leaf blade to total nitrogen was higher than that of dry matter at
      either growth stages. Dry matter, nitrogen, phosphorus accumulated at ripening
      stage were mainly distributed in panicle with rates of 58.01%, 66.42% and 70.06%,
      respectively. But potassium accumulated at ripening stage was mainly distributed
      in stem and leaf sheath with the rate of 62.08%. Silicon was largely distributed
      in stem and leaf sheath at early season with the rate of 43.11%, but distributed
      largely in panicle at late season with the rate of 46.99%.

PMID- 15146629
TI  - [A dynamic knowledge model for wheat target yield design and variety selection].
AB  - Based on integrating the effects of yield potential of photosynthesis and
      temperature, average yield level of last three years, soil fertility,
      fertilization and water management level and production technology level on yield
      increment, the dynamic yield increment index was quantified and a wheat knowledge
      model for design of target yield under different temporal and spatial
      environments was developed through knowledge engineering and system analysis
      method. By quantitatively calculating suitability of variety characteristics to
      environmental conditions and production requirements, a knowledge model for
      variety selection was established. Case studies on the target yield design with
      the data sets of five different eco-sites, three climatic years and average yield
      levels of last three years, two soil fertility levels and three fertilization and
      water management levels, and on suitable variety selection models with the data
      sets of five different eco-sites, normal climatic year and fifteen typical
      varieties indicated a good performance of the model system in decision-making and
      wide applicability.

PMID- 15146630
TI  - [Microbial eco-characterization and its restoration in copper reclaimed wasteland
      in red soil area of China. II. Effects on soil microbial characteristics and
      community structure].
AB  - Soil microbial features in Lipu copper mining and non-mine soil were studied
      comparatively. The results indicated that mine soil possessed obviously different
      microbial features such as lower microbial biomass carbon and soil basal
      respiration strength, Cmic/Corg decreasing, and higher microbial ecophysiological
      parameters qCO2, indicating that heavy metal had a depressive impact on soil
      microbial eco-characteristics. Biolog data showed that mine soil microbial
      community structure was changed obviously, the speed and quantity of carbon
      consuming were increased significantly, and the kinds of carbon sources which
      soil microorganism used were changed, led to consume much more energies for
      maintaining the normal needs of its life. But the utilization efficiency was
      lower compared with the control. All the results showed that soil microbial eco
      characteristics could be used as a sensitive, effective and liable index of mine
      soil environment qualities.

PMID- 15146631
TI  - [Modification and its application of generalized Schumacher model].
AB  - Based on the concrete analysis on growth equations presented by others, a
      modified Schumacher growth equation was proposed as, which included Gompertz
      function, Schumacher equation and generalized Schumacher equation, and had
      stronger self-adaptability and practicality. The analytic character and
      adaptability of the modified Schumacher equation were analyzed. According to the
      genetic algorithms method, this model was used to fit the growth data of
      endangered plant of Tsuga longibracteata and Platycladus orientalis. The results
      showed that the modified Schumacher equation was not only better than Schumacher
      equation and generalized Schumacher equation significantly, but also better than
      classical Logistic model and Li's self-adaptive model. So it could be used to
      study the dynamics simulation for tree growth and dynamics law for population
      growth.

PMID- 15146632
TI  - [Problems in development of agriculture-animal husbandry ecotone and its
      countermeasures].
AB  - Problems in development of Duolun, a typical agriculture-animal husbandry
      ecotone, and its countermeasures were discussed in this paper. Economic structure
      was not rational in Duolun, and it should develop industry and commerce, limit
      the scope of agriculture and animal husbandry, and actively increase efficiency
      of agriculture and animal husbandry. The structure of land use was not rational,
      and the main countermeasures were to increase area of forestland and grassland,
      and decrease cultivated area. On resources use, the main countermeasures were to
      exploit water resource rationally and bring into play resource superiority of
      mutually benefits on agriculture and animal husbandry. The ecological environment
      construction was the foundation of the national economy for sustainable
      development in agriculture-animal husbandry ecotone.

PMID- 15146633
TI  - [Analysis on the dynamics of desert-oasis vegetation in the Sangong River Basin].
AB  - Taking the Sangong River Basin as a typical research area, the relationships
      between the change of landscape pattern of desert-oasis and the dynamics of
      vegetation were studied in this paper, and the evolution of the landscape pattern
      of desert-oasis was also discussed. The results showed that the main
      characteristics of landscape pattern were the dynamics of vegetation. It had the
      impact on the vegetation by the changes of topography, water resources using,
      corridor of river and drainage channel. It was shown the great variability for
      the height, cover and biomass of vegetation with the change of landscape pattern.
      Taking the corridor of river as the center, it usually showed a zone distribution
      from inside to outside for the desert-oasis landscape pattern. The vegetation
      types evolved from the tree-shrub mixed forest, thicket meadow, salinized meadow
      to desert with the change of the condition of water and heat in the basin. The
      stability of natural patch was higher than that disturbed by mankind or manmade
      patch. Usually, the stability of each patch was in order of desert > sandy land >
      urban > pond > paddy field > grass land > vegetable plot > woodland > residential
      area > saline-alkali land > wasteland > farming land > orchard. The landscape
      pattern of desert-oasis in the research area was developed by human activities
      based on natural oasis.

PMID- 15146634
TI  - [Establishment and growth of Lolium multiflorum for phyto-remediation of Pb/Zn
      tailings].
AB  - Following the cropping of Sesbania rostrata, Lolium multiflorum was cropped as
      the subsequent species on an acidified Pb/Zn tailings site. As the experimental
      treatments, S. rostrata issues harvested on the site were removed from the site
      or buried into the tailings as the green manure. Changes of tailings chemical and
      physical properties, germination, growth and heavy metal accumulation of Lolium
      multiflorum were investigated. The results showed that cropping of S. rostrata
      improved the chemical and physical properties of the tailings, especially for the
      contents of organic matter, total nitrogen, available phosphorus and available
      potassium. The strong acidity (pH < 3) in the Pb/Zn tailings was the main factor
      that limited the establishment of L. multiflorum. The tailings acidity was
      decreased temporarily by lime application and it seemed to be helpful only for
      the germination because the strong acidity was restituted in the end of the
      experiment. In the most cases, L. multiflorum succeeded to germinate, grow and
      establish on the Pb/Zn tailings, and yielded relatively great biomass (DM 1.4-3.2
      t.km-2). Compared to CK (without S. rostrata cropping), cropping S. rostrata
      increased the biomass of subsequent L. multiflorum by 4.8%-39.5% in case without
      S. rostrata green manure using and by 7.7%-139.5% in case with the green manure
      using, and the green manure application resulted in 2.7%-75.8% increment of L.
      multiflorum biomass. The results proved that the artificial vegetation process
      using S. rostrata and subsequent L. multiflorum would be a successful pioneer
      stage for restoration of the Pb/Zn tailings.

PMID- 15146635
TI  - [Effects of different light transmission rate on American ginseng's
      photosynthesis].
AB  - From 1997 to 1998, series of experiments were carried out to study American
      ginseng's photosynthesis related to light transmission rate of plastic cover. The
      results showed that American ginseng's light saturation point for photosynthesis
      was different under the different light transmission rate (LTR) because of
      shading. At about 29.0 degrees C and under 12%, 30%, 42% LTR, 4-year-old American
      ginseng's light saturation point were 171.0, 323.0, and 429.0 mumol.m-2.s-1,
      respectively. The maximum net photosynthesis rate (Pn) was 6.54 mg CO2.dm-2.h-1,
      which appeared under the shading of 30% LTR. The daily course of 3-year-old
      American ginseng's Pn changed with LTR. When LTR was less than 25.8%, the daily
      curves of Pn had a single peak, and when LTR was higher than 25.8%, it had two
      peaks and the leaf's photosynthesis noon break phenomenon was remarkable. The
      results of single correlative analysis showed that the dominant factor that
      influenced Pn was photon flux density (PFD), and the results of plural regression
      analysis showed that the synthetic effect of all the influencing factors together
      on Pn was significant.

PMID- 15146636
TI  - [Vertical distribution character of nutrient elements in peat of Sanjiang Plain].
AB  - Based on the methods of sampling in winter and dividing soil layer on the site,
      the vertical distribution character of normal amount nutrient elements N, P, Mg,
      Ca, Fe and nutrient trace elements Cu, Zn, Mn, B in peat of river bed-flood land
      and valley depression land in the Sanjiang Plain was studied systematically. The
      results showed that TN was accumulated in surface layer of peat, and TP was
      accumulated in root layer. The contents of TN and TP were decreased with the
      section depth increasing. Zn, Mn, B, Mg and Fe were gathered in root layer and
      accumulated sharply in gley horizon of silt sub-clay, and the content of Ca was
      regular relatively in each layer of section. There were close correlations among
      some nutrient elements in peat section.

PMID- 15146637
TI  - [Spatial pattern analysis of forest landscape in low coteau of middle Qilian
      Mountains].
AB  - Based on the vegetation map and the relief map, using GIS and Fragstats, the
      spatial pattern of forest landscape of Xishui reserve in Qilian Mountains were
      analyzed. The results showed that the distribution of the vegetation was impacted
      mostly by altitude and aspect, grasslant was mostly distributed on the land of
      altitude 2,500-2,900 m and aspect of south and southwest, Picea crassifolia
      forest was always in the land of altitude 2,900-3,300 m and aspect of north,
      northeast, east and northwest, and shrubbery was in the land of altitude 3,300
      3,700 m. The grassland had the biggest area and its connectivity and integrality
      were the best. The biggest MPFD of Picea crassifolia forest meant that its shape
      was the most complicated, its mean patch area was small, and the distance between
      the patches was short. So Picea crassifolia forest was easy to be impacted by
      some disturbance. The forest suitable land and Sabina przewalskii forest showed
      more outstretched characteristics than farmland and land with few trees. The mean
      nearest-neighbor distance of the poplar forest was the biggest in all the
      landscape elements, so the poplar forest's fragmentized degree was the highest in
      all the landscape elements.

PMID- 15146638
TI  - [Analysis of the landscape diversity dynamics of small watershed in the Loess
      Plateau].
AB  - Taking Zhifanggou Gully as the study area, some landscape diversity indexes were
      attained under the support of GIS technology. Utilizing the indexes such as patch
      size, average fractal dimension, diversity index, dominance, evenness,
      fragmentation and conglomeration, the changes of landscape diversity in the small
      watershed in Loess Plateau during the past 40 years were studied. The landscape
      diversities had been increasing for the recent 40 years due to the effect of both
      human activity and plants' endogenesis succession. The patches number increased,
      and the dryland matrix was substituted gradually by other matrixes such as meadow
      and woodland. The landscape pattern trended to be fragmentized and the indexes of
      landscape type diversity and evenness increased, while landscape diversities
      changed greater during 1978-1998 than during 1958-1978. Homogeneous dryland
      matrix landscape ecosystem in 1958 had already changed into heterogeneous meadow
      and woodland matrix landscape ecosystem, which had greater structure stability
      and stronger function than before.

PMID- 15146639
TI  - [Distributed modeling of nutrient transport in basin with support of remote
      sensing and geography information system].
AB  - Agricultural non-point source pollution has become serious in our country.
      Modeling the processes of nutrient(especially nitrogen and phosphorus) transport
      in basin and evaluating the adopted management practices are important for
      controlling the impact of non-point pollution on environment. A research scheme
      for distributed simulation of nutrient transport processes in Lianshui Basin,
      Xingguo County, Jiangxi Province was designed, with the support of remote sensing
      (RS) and geography information system (GIS). The research procedure included
      model selection, discretization and spatial parameterization of the basin,
      prediction, and validation. SWAT model was selected, and basin-subbasin
      hydrological response unit discretization scheme was designed. Supported by RS
      and GIS and based on the topographic features of the watershed, the subwatershed
      discretization divided the watershed into subbasins, and each subbasin could be
      further partitioned into multiple hydrologic response units (HRUs), which were
      unique soil/land use combinations within the subbasin and modeled through
      statistical spatial overlay analysis. The parameters of land use were obtained
      from the supervised classification of TM imagery based on field training samples,
      and those of soil were obtained from field sampling and further interpolated
      through geostatistical method. The simulation was carried out by using the data
      from 1991 to 2000. The results showed that the simulation accuracy of annual
      runoff water yield and sediment yield was 89.9% and 70.2%, respectively.

PMID- 15146641
TI  - [Distribution and stock of mercury in typical wetland plant in the Sanjiang
      Plain].
AB  - Total mercury concentration of typical wetland plant was analyzed. There were
      great difference in mercury content among different plants, and the order was
      moss > alga > carex > herb > shrub. There was a trend of increasing total Hg
      concentrations from vascular plants to bryophytes, and from dry to wet site. The
      wetland soil was the source of mercury in the air close to the ground, so it
      influenced the content of mercury in the plant. In different components of
      plants, mercury contents were in the order of dead stand > root > leaf > stem.
      Mercury concentration increased in initial stage and decreased in the end of the
      growing season. According to the mercury content and biomass, the mercury stock
      of plant were calculated, and it was 24.9 micrograms.m-2 in the above ground of
      plant in Calamagrostis angustifolia wetland and 35.8 micrograms.m-2 in Carex
      lasiocarpa wetland.

PMID- 15146640
TI  - [Spatial distribution and landscape ecological impact degree assessment of quarry
      in Zhuhai City].
AB  - Artificial erosion is one of the typical artificial landscape degradation. Based
      on the support of GIS and RS and combined with field investigation data, the
      spatial distribution characteristics and landscape ecological impact degree of
      quarry were analyzed. There were 235 quarries in Zhuhai city, which concentrated
      on Sanzao town and Jingan town. According to buffer analysis, the quarries
      distribution had a obviously logarithm relationship with its distances from
      roads. 152 quarries with the area of more than 5000 m2 were assessed by landscape
      ecological impact degree (LEI) index. The results indicated that 9 quarries
      belonged to great influence level and 19 quarries belonged to strong influence on
      ecological environment.

PMID- 15146642
TI  - [Difference of lead uptake and distribution in rice cultivars and its mechanism].
AB  - In order to investigate the uptake of lead by rice plant and the distribution of
      lead in different parts of rice, pot experiment was conducted with 20 rice
      cultivars of different genotypes by adding lead to soil. The results showed that
      there existed significant differences among the cultivars in the lead uptake and
      distribution by rice plants, but the differences had no obvious relationship with
      rice genotypes. The lead concentrations decreased rapidly from roots to grains
      along rice plants, so the concentrations of lead were very low in grains compared
      with other parts of rice plants. The regression analysis showed that there were
      significant negative correlations between adjacent organs of rice plant, but
      positive correlations, mostly significant, between disconnected organs, for the
      lead concentrations in them. Lead concentration in the leaf of heading stage
      showed a significant positive correlation with that in the grain of ripening
      stage. Lead was not distributed uniformly in different parts of grain structure,
      and the lead accumulation in polished rice was only 32.88% of the total lead
      accumulation in grain.

PMID- 15146644
TI  - [Host plant suitability and reproductive isolation of two Schizotetranychus
      bambusae populations from the bamboo species Phyllostachys pubescens and
      Neosinocalamus affini].
AB  - Development, survivorship, reproduction and procreation isolation of
      Schizotetranychus bambusae from the bamboo species Phyllostachys pubescens and
      Neosinocalamus affinis reared on different host plants were evaluated in
      laboratory. The results showed that the population of S. bambusae from
      Phyllostachys pubescens (PhS) failed to complete its life cycle when reared on
      the leaf of N. affinis. When the population of S. bambusae from N. affinis (NeS)
      was reared on the leaf of P. pubescens, the survivorship and fecundity decreased.
      The rm, lambda and Ro were 0.0391, 1.0399 and 2.5542, respectively. At 27 degrees
      C, when the PhS was reared on P. pubescens, rm, lambda and Ro were 0.1415,
      1.1520, and 15.6298, respectively, whereas NeS was reared on N. affinis, rm,
      lambda, and Ro were 0.0993, 1.1044, and 10.0622, respectively. Reciprocal cross
      test between PhS and NeS showed tht the two populations could mate, but laid
      unfertilized eggs that produced male only, indicating the existence of
      reproductive isolation.

PMID- 15146643
TI  - [Degradation of methyl parathion in soil and Chinese chive by strain DLL-1].
AB  - Degradation of methyl parathion in soil and Chinese chive by strain DLL-1 was
      studied. Usage of methyl parathion at 7.5, 15, and 22.5 kg(a.i.).hm-2 resulted in
      the average amount of residue of 0.663, 1.270, and 1.901 mg.kg-1 in Chinese chive
      respectively. The natural degradation rate was 98.94%, 96.44%, and 96.04%
      corresponding to the 3 levels of usage. The amount of pesticide residue could be
      significantly decreased through the application of high effective degrading
      microbial agents. The amount of pesticide residue in Chinese chive and soil was
      0.269 and 0.099 mg.kg-1 with the usage of 75 kg.hm-2 of degradation bacterium,
      which was decreased by 78.82% and 98.68% compared with the control. Increasing
      the bacterium usage led to the increase of degradation rate. Usage of degradation
      bacterium more than 75 kg.hm-2 did not increase the degradation rate further. The
      best time of the application of the degrading microbe was 3 days after the
      application of the pesticide.

PMID- 15146645
TI  - [Cooperative effect of Spodoptera litura nuclear polyhedrosis virus with parasite
      wasp, Microplitis sp. on the S. litura larvae].
AB  - The relationship between the survival rate, developmental duration of Microplitis
      sp. in Spodoptera litura larvae and time of exposure of the host larvae to virus,
      the inoculation virus concentration were investigated to determined if parasites
      which emerged from virus-infected S. litura larvae had normal survive, and if the
      parasites could sever as the vector for S. litura nuclear polyhedrosis virus
      (SINPV). There was no significant difference in time that parasites spent in
      virus-infected larvae and healthy one, indicating the SINPV did not affect the
      developmental period of Microplitis sp. Parasite larvae in hosts exposed to virus
      after parasitization compmeted their development before their hosts died of virus
      infection. The proportion of parasites survived varied with the inoculation virus
      concentration and the time of exposure of the host larvae to virus, the percent
      of parasites survived increased as the time between host parasitization and host
      virus exposure increased, and decreased as the inoculation virus concentrations
      increased. The female parasites which developed or oviposited in virus-infected
      hosts, and manually contaminated the ovipositor of the females with virus
      suspension could all carry infective doses of the virus, and transmit virus from
      infected larvae to healthy one through ovipositor. A female parasite which
      developed or oviposited in virus-infected hosts transmitted infective doses of
      the virus to an average of 2.14, 2.45 healthy host larvae exposed to it
      respectively. A female parasite from the cocoon contaminated with SINPV of
      different virus concentration could transfer infective doses of the virus to an
      average of 1.45 healthy host larvae. A female parasite exposed to the mixture
      different virus concentration and 10% honey-water solution could also transmit
      virus to an average of 0.94 larva.

PMID- 15146646
TI  - [Population dynamics of Microtus fortis in Dongting Lake region and its
      forecasting].
AB  - The population dynamics of Microtus fortis in Yueyang, Hunan Province was studied
      from 1991 to 1996. M. fortis lived on the beach of the lake from early autumn to
      next spring, but moved to the farmland in summer when the beach was flooded. When
      lived on the beach, its population increased gradually. Usually, M. fortis made
      great damage on the crops when moved to the farmland. The population dynamics of
      M. fortis was different on the beach and on the farmland, and the key affecting
      factors were also different. Lake beach was the most suitable habitat for M.
      fortis. When it emerged in autumn, M. fortis moved back on it. The main breeding
      season of M. fortis inhabited on the beach was from October to May, and its
      population density increased gradually. The period between the beach emerged and
      been flooded determined the population size of the animal moved to farmland.
      Another factor was the rainfall in March. Farmland was not the suitable habitat
      for M. fortis. Because of the low breeding potential, high mortality and
      dispersal on farmland, its population density kept decreasing, and was very low
      in winter. The population density on farmland dropped dramatically when the lake
      beach emerged. The animal population was forecasted by means of regression
      analysis, and a linear regression equation was obtained. The predicted values
      matched with the real population densities of the animal in the field.

PMID- 15146648
TI  - [Methodology of enacting standards for remediation of contaminated soils].
AB  - Remediation technology for contaminated soils is being developed rapidly in
      recent years. However, there is a hysteresis in enacting remediation standards
      for contaminated soils. In particular, no corresponding research has been done in
      China. Methodology of enacting standards for the remediation of contaminated
      soils is discussed in order to promote the work in this field. It is emphasized
      that technological cleanup levels including limits of detection, environmental
      background levels and regulatory cleanup levels should be fully considered in the
      enactment of remediation standards.

PMID- 15146647
TI  - [Suspending particulates in rotifer-culturing pond ecosystem].
AB  - A comparative study on the structure and dynamics of suspending particulates in
      static and current water rotifer-culturing ponds showed that the total content of
      suspending particulates varied from 6.76 to 65.39 mg.L-1, with an average of
      11.50 mg.L-1 in static water ponds, among which, organic pariculates accounted
      for 66.8%, while inorganic particulartes occupied 33.2%. In the organic
      particulates, both particulate detritus and bacteria accounted for 31%, while
      phytoplankton and zooplankton occupied 30.5% and 5.3%, respectively. The amount
      of suspending particulates in current water ponds was 41.83 mg.L-1 in average,
      among which, organic pariculates accounted for 70.4%, while inorganic pariculates
      occupied 29.6%. In the organic pariculates, both particulate detritus and
      bacteria accounted for 39.2%, while phytoplankton and zooplankton occupied 30%
      and 1.2%, respectively. The content of suspending pariculates in static water
      ponds was less than those in current water ponds. Rotifer-culturing pond was a
      special type of ecosystem, where Brachionus plicatilis was the major consumer,
      its community structure was sample, and the abiotic factors were easy to be
      changed, which resulted in the dynamics of suspending pariculates content in
      ponds. The ratio of organic to total pariculates in rotifer-culturing ponds was
      higher, and the contents of both particulate detritus and bacteria were
      corresponding to that of plankton.

PMID- 15146649
TI  - [Research advance in ecotoxicology and environmental impact of veterinary
      medicines].
AB  - Veterinary medicines or their metabolites could be discharged to the environment
      through different exposure routes, and had potential impacts to ecosystem in
      different levels, including individual, population, community and ecosystem.
      Their fate and potential impact have been widely researched in the world. This
      paper reviewed their exposure routes, fate in the environment, and impact on
      organisms in soils and waters and on soil processes. The significance of their
      environmental risk assessment was also analyzed.

PMID- 15146651
TI  - [Physiological adaptations of sichuan golden monkeys (Rhinopithecus roxellana) to
      high altitude habitat in the Qinling Mountains].
AB  - The golden monkey (Rhinopithecus roxellana) is a special species in China, and
      possesses the highest altitude habitat (4,167 m) in all kinds of primates. So it
      is very important to study this monkey how to adapt to such a high and severe
      habitat. According to our research results in recent years and relative
      publications, this paper, from digestive, respiratory, blood, circulative and
      reproductive systems, inquired into the Sichuan golden monkey (Rhinopithecus
      roxellana), a named species for golden monkey, how to adapt to the high altitude
      habitat in the Qinling Mountains and what was the mechanism of these adaptations.

PMID- 15146650
TI  - [Influence of dissolved organic matter (DOM) on environmental behaviors of
      organic pollutants in soils].
AB  - Dissolved organic matter (DOM) is an important component of solutions in
      terrestrial and aquatic ecosystems through its influence on acidity, nutrient
      availability, and toxicity. DOM could enhance the apparent solubility of organic
      pollutants and alter adsorption-desorption equilibrium of organic pollutants on
      soil. The enhancement of organic pollutants desorption in the presence of DOM
      could facilitate the mobility of organic pollutants in soil. On the other hand,
      the sorption of DOM by solid sorbents in soil could also enhance the retention of
      DOM-associated organic pollutants in soil. Furthermore, as a photosensitizer, DOM
      could promote the photogradation of organic pollutants in soil. And under certain
      condition, DOM also affected the hydrolysis of organic pollutants in soil
      solution. The effects of DOM on environmental behaviors of organic pollutants in
      soils were related to the physico-chemical characteristics of organic pollutants,
      DOM, and soil.

PMID- 15146652
TI  - [Conservation tillage systems in North America and their significance for China].
AB  - Soil degradation through erosion and desertification reduces soil productivity,
      and is a serious problem in agricultural production of China. To avert our arable
      land from further degradation, soil management must be shifted from degrading
      tillage to conservation practices. Over viewing the technology used in the 20th
      century for controlling soil degradation from erosion, conservation tillage
      developed in the United States and adopted in South America and Africa is one of
      the most successful measures to overcome soil degradation problems. This paper
      reviewed the historical development and the current situation of conservation
      tillage systems used in North and South America, with special reference to their
      effects on soil erosion control and soil quality. The increasing adoption of
      conservation tillage systems in North and South America and Africa followed an
      enhanced awareness of the increasing risk of soil erosion and the high cost of
      fuel associated with conventional tillage. Many crucial points for successfully
      adopting conservation tillage systems were emphasized, such as equipment/tool
      development and chemical weed control. Adopting conservation tillage could
      provide China with low-priced means of reducing soil degradation and improving
      soil and water quality.

PMID- 15146653
TI  - [Impact of pesticides on biodiversity in agricultural areas].
AB  - Large amount application of pesticides caused a lot of ecological and
      environmental problems, among which, the impact of pesticides on biodiversity was
      most important. In this paper, an overview of the impacts of pesticides on
      biodiversity in agricultural areas, including the community structure of insects,
      populations of soil invertebrates and microorganisms, and plant communities was
      provided, and the reasonable use of pesticides and the measures of protecting
      biodiversity in agricultural areas were also put forward.

PMID- 15146654
TI  - [Effects of rice volatile infochemicals on insects].
AB  - Plant volatile is not only the key of the relationship among plant, herbivore and
      its natural enemy, but also the foundation for the theory and practice of pest
      manage. In this paper, the chemical characteristic of rice volatile and its
      function among herbivore and its natural enemy were reviewed. The application and
      development direction of rice volatile infochemicals were proposed. Two
      directions to study the rice volatile infochemicals, which could be used in pest
      control, were also discussed. One was the physiology and biochemistry of little
      molecule signals, which was the key of rice second metabolize, and the other was
      the base of sense, identify and learn of pest insect to rice volatile
      infochemicals.

PMID- 15146655
TI  - [Forest health ecological risk assessment in China].
AB  - Forest health ecological risk assessment is an important factor in forest
      resources management. In this paper, we selected forest fire, forest disease-pest
      disasters and acid rain as main risk sources, described the risk resources by
      probability, intensity and distributing, and mapped each risk source. The
      endpoints were the damages that the risk acceptor might and these damages might
      cause ecosystems' organization and function changing under the uncertainty risk
      sources. Endpoints of forest might compose of productivity descent, reducing
      biodiversity, forest degrading, forest ecological function declining,
      furthermore, forest disappearing. We described exposure in terms of intensity,
      space, and time. In the exposure and hazard analysis, we used fragile index to
      show frangibility or resistibility (resistibility is reverse to frangibility),
      and analyzed the damages by different risk sources. Risk assessment and
      management was the integrated phase of the research. Because of the spatial
      heterogeneity of risk sources, all risk index were overlaid in the China map by
      GIS, which divided the region into 30 ecological risk sub-zones (provinces),
      according to risk index of each risk sub-zone, and the forest in China was
      divided into six levels of risk zones. In every level of risk zones, we also put
      forward the countermeasures for forest health ecological risk management. The
      result of assessment could provide scientific basis for forest management.

PMID- 15146656
TI  - [Application of artificial neural network based on the genetic algorithm in
      predicting the root distribution of winter wheat].
AB  - In this study, a controlled experiment of winter wheat under water stress at the
      seedling stage was conducted in soil columns in greenhouse. Based on the data
      gotten from the experiment, a model to estimate root length density distribution
      was developed through optimizing the weights of neural network by genetic
      algorithm. The neural network model was constructed by using forward neural
      network framework, by applying the strategy of the roulette wheel selection and
      reserving the most optimizing series of weights, which were composed by real
      codes. This model was applied to predict the root length density distribution of
      winter wheat, and the predicted root length density had good agreement with
      experiment data. The way could save a lot of manpower and material resources for
      determining the root length density distribution of winter wheat.

PMID- 15146657
TI  - Medical workforce planning in Australia: process, methodology and technical
      issues.
AB  - This article describes the process, methods and technical issues associated with
      national level planning of the medical workforce in Australia. In Australia,
      workforce planning is also undertaken for the nursing and allied health
      workforces using largely similar processes and methods outlined below, with
      obvious modifications for differences in data sources, structures and practice.
      In Australia, the focus is also switching to a more integrated planning approach
      along care group lines, for example emergency care, diabetes care. This approach
      is still in its infancy and some technical and methodology issues are unresolved.
      Much of the health workforce planning in Australia is undertaken at the national
      level through the research team at the National Health Workforce Secretariat,
      although some work is also undertaken by individual jurisdictional health
      departments and other stakeholders. Information about the national health
      workforce agenda and the outcomes of the research and analysis is available
      through the Health Workforce Australia website at
      http://www.healthworkforce.health.nsw.gov.au. It should be acknowledged that the
      main sections of this article have been summarised from the 2003 publication
      Specialist Medical Workforce Planning In Australia, prepared by the Australian
      Medical Workforce Advisory Committee and the National Health Workforce
      Secretariat.

PMID- 15146658
TI  - The medical profession in Germany: past trends, current state and future
      prospects.
AB  - In conclusion, the shortage of doctors can be described as a pincer movement. The
      German medical profession is both superannuated and faces difficulty recruiting
      new young doctors. The shortage of doctors in Germany is thus not caused by a
      mass exodus of those already working in the system but by the reluctance of young
      doctors to work in curative medicine. This shortage of doctors is already
      apparent in the statistics. Last year the number of doctors active in ambulatory
      medicine dropped in the areas of four State Medical Associations (Brandenburg,
      Mecklenburg-West Pomerania, Saxony and Saxony-Anhalt). Moreover, in Saxony-Anhalt
      the number of the hospital doctors also declined so that this state was faced
      with a 1.1% fall in the number of working doctors. The Saarland also recorded a
      fall in the number of active hospital doctors. The conclusion must be that the
      standard conditions for doctors must be made more attractive so that young people
      take more interest in curative medicine. If this does not happen, there will be
      bottlenecks in the supply of medical care on a broad front in Germany. In the
      end, the provision of medical care for the population as a whole could be
      jeopardised.

PMID- 15146659
TI  - [Health workforce forecasting carried out by the C.S.D.M. (1964-2004)].
AB  - During the last 4 decades, the Centre has performed 16 pieces of forecast on the
      various health professions in France, the majority being devoted to medical
      doctors. During the 60's, information were scarce, and calculations on both the
      inflows of future new graduates and the outflows of future deaths and retirements
      could not reach an acceptable level of relevance. In 1972, a numerus clausus
      system was established at the beginning of medical training. Moreover, efforts
      were deployed to collect better data and improve projection techniques. All these
      factors contributed to raise strongly the quality of the forecasting work. The
      discrepancies between the projected and actual trends were narrowing, as showed
      below: [table: see text] The forecasts were based on the demographic projection
      techniques and the results obtained showed not only the total number of active
      physicians in the country but equally the distribution by age groups of this
      total number. The latter element allows the predictions of the aging process of
      the medical profession as an impact of the present-day policies concerning
      medical student intake (numerus clausus).

PMID- 15146660
TI  - [Demographic forecasts of medical workforce supply in France (2000-2050). What
      numerus clausus for what future?].
AB  - In France, medical training and graduation of medical doctors are under the full
      control of the State. A numerus clausus barrier is established between the first
      year and the second year of medical schools. The first year is open to all
      students having successfully completed their secondary schooling (18 years old)
      but the number of those allowed to start the second year is decided every year by
      the government. Foreign medical graduates can practise only if they have obtained
      authorization from the State. Theoretically, the authorities have all means for
      shaping the size of the medical workforce, either in the short term (e.g. by
      importing foreign medical graduates to fill up vacant posts) or in the long run
      (by increasing or decreasing the numerus clausus, or student intake, to cope with
      shortage or oversupply of doctors). In practice, due to various constraints, the
      issue is far from simple (resistance to change, divergent lobbying forces and,
      more importantly, lack of relevant information). METHODS: In this study, the
      forecasting techniques of demography are used to assess the future trends of
      supply of medical doctors, on the basis of the formula t2 = t1 + e - l t1 is the
      medical workforce at the beginning of the period t2 is the medical workforce at
      the end of the period e is the number of doctors entering the medical workforce
      (new national graduates or foreign graduates) during the period l is the number
      of doctors leaving the medical workforce (death, retirement, out migration)
      during the period. Calculations are performed for each 5-year age group and for
      the successive 5-year periods. At the end of a 5-year period, one obtains the
      number of professionally active doctors in each 5-year age group and, by
      addition, the total number of active physicians in the country. The starting
      point of the projection work is December 31st 2000 when the French medical
      profession numbered 200,800 (i.e. 334 physicians per 100,000 population). As
      concerns the inflow e (physicians entering the profesion), calculations are
      performed step by step: number of students starting the 2nd year of medical
      schools: two basic hypotheses are adopted as concerns the future intake decided
      by the government, 8000 and 6000 (Table A) from the numerus clausus barrier (2nd
      year of medical training) to the 6th year of medical training from the 6th year
      to graduation (the residency period) from graduation to registering in the
      Medical Council (effective start of the career) moreover, it is assumed that from
      2000 through 2025, for each 5-year period, 1200 foreign medical graduates are
      allowed to join the national medical workforce; after 2025, this number will
      decrease to 300. As concerns the outflow l, a "professional life table" is used
      to determine the numbers of doctors of each age-group who leave the career by
      death, retirement, outmigration ... during each 5-year period (Table B). CONTEXT:
      From 1965 onwards, the number of students entering the medical schools grew
      steadily. The numerus clausus system, established in 1972, became effective five
      years later. However, due to resistance to change, the number of students allowed
      to start the 2nd year of medical schools reached a really low level only at mid
      80's. In other words, during the period 1974-1994, France experienced a
      significant "graduate boom". The young doctors graduated during these two decades
      were in extremely high numbers and fueled a strong feeling of manpower
      oversupply. But from mid-90's onwards, the annual number of new graduates
      decreased (as a result of the low numerus clausus decided from mid-80's). In
      hospitals, post vacancies became frequent. In ambulatory care, medical
      practitioners encountered great difficulties to find locum tenens. From 2000
      onwards, the term of manpower shortage was openly evoked in public debates.
      Starting 1999, the authorities increased again the numerus clausus which reached
      5100 in October 2003. The mood was in favor of an upward trend. As a matter of
      fact, the numerous physicians graduated during the 1974-1994 boom period will
      begin to retire around the year 2010 and the French medical profession would
      sharply decrease without a vigorous growth of the numerous clausus. As started
      above, this projection work adopts two basic hypotheses as concerns the numerus
      clausus: the number of medical students allowed into the 2nd year, will
      progressively increase in October 2007 either to 6000 or to 8000 and will remain
      constant later on. RESULTS: With a 8000 student intake, the number of physicians
      (200,800 in 2000) will increase to 209,300 in 2010 then will slowly decrease to
      205,900 in 2030. After, it will grow again and reach 229,500 in 2050. With a 6000
      student intake, the number of physicians will also increase to 209,300 in 2010,
      then will rapidly decrease to 173,700 in 2030. The downward trend will stop in
      2035. After, a slow growth will take place and the medical profession will number
      173,500 in 2050 (Table C and Fig. 1). In other words, if a numerus clausus of
      8000 is decided, the large retirement of the 1974-1994 graduate boomers (during
      the period 2010-2030) will be nearly offset by the newcomers. At the same time,
      the aging of the medical workforce will be stopped. Instead, a new younging
      process of the medical profession will take place again after 2020 (Fig. 2 and
      Fig. 3). As it was the case during the early 70's, the younging process or
      pouring in of new graduates in great numbers may possibly fuel a strong
      perception of oversupply and lead to a sharp decrease of the numerus clausus
      after 2020 (sec variants Ib, Ic, IIb, IIc in Table A and C). As the numerus
      clausus has been increased during the first decade of the century, the two
      opposite moves (upward and downward) will create once again a phenomenon of
      "graduate boom". The boom will be far more important with a student intake of
      8000 (Table F and Fig. 5) than a student intake of 6000 (Table G and Fig. 7).
      Even with 8000 students, the boom will not appear if the intake (numerus clausus)
      is not decreased after 2020. Consequently, if the decision is made today to
      increase sharply the student intake, we should be sure not to have to decrease it
      strongly in two or three decades. A less important increase decided today will
      not totally fill the gap when those graduated during the period 1974-1994 will
      retire and the national number of physicians will diminish. But such a decision
      will probably avoid the appearance of a feeling of oversupply in the coming
      decades and its subsequent problems (decreased student intake and, a decade
      later, a new graduate boom).

PMID- 15146661
TI  - [Existential crisis of the dying physician].

PMID- 15146662
TI  - [From starvation to abundance--a changed disease panorama].

PMID- 15146663
TI  - [Contribution of stress to the development of the metabolic syndrome. In memory
      of Per Bjorntorp (1931-2003)].

PMID- 15146664
TI  - [Clinical psychoacoustics can support an objective diagnosis of schizophrenia].
AB  - This article deals with a new branch of research in psychiatry focusing upon
      schizophrenia in the first hand. Methods of investigating psychoacoustic
      aberrations in this disease have been developed during the last twenty years at
      our laboratory; Unit of Clinical psychoacoustics, Division of Psychiatry, Dept of
      Clinical Neuroscience, Lund University (www.psykiatr.lu.se/psykoaclab).
      Schizophrenic persons show dysfunctions at the psychophysiological level as
      displayed by many psychoacoustic mechanisms such as streaming, restoration and
      contralateral induction of sounds. These dysfunctions may influence general
      cognitive and perceptual processes and partly explain clinically observed
      symptoms of the disease. Further investigations on the efforts to elucidate
      normal functioning of the psychoacoustic processes by functional magnetic
      resonance imaging, auditory brainstem response and via animal models are
      described. One immediate aim of all the studies is to be able to demonstrate
      objective measurements of the schizophrenic aberrations using psychoacoustic
      tests. This would help supporting the diagnosis, setting early diagnosis or guide
      therapeutic decisions.

PMID- 15146665
TI  - [8 out of 10 midwives informed about folic acid. Most of them considered their
      knowledge about folic acid not sufficient].
AB  - Deficiency of folic acid increases the risk for neural tube defects among newborn
      children and megaloblastic anaemia in the mother. The aim of this study was to
      make a survey of how midwives working in maternity health care, family planning
      guidance, and specialist prenatal care in a Swedish county inform women of
      childbearing age about folic acid. The questionnaire study showed that 79% of the
      midwives informed the women about folic acid. Usually, the women received
      information first when they asked for it and midwifes were less prone to inform
      young women about folic acid. 87% of the midwives felt that they did not know
      enough about folic acid. CONCLUSIONS: Midwives play an important role in
      information about the need of folic acid intake for women in childbearing age.
      Changes in local routines, guidelines and further education of midwifes would
      subsequently provide information about the importance of folic acid to women in
      childbearing age.

PMID- 15146666
TI  - [Exercise and experienced health among middle aged men and women. Physically
      active individuals feel better].

PMID- 15146668
TI  - [Training for improved body awareness and relaxation for stress management].

PMID- 15146669
TI  - [Computer arm--a new kind of pain problem].

PMID- 15146670
TI  - [Check lists and screening--a threat against the consultation].

PMID- 15146667
TI  - [Physical activity as prophylaxis and treatment of stress-related conditions].

PMID- 15146671
TI  - [Risk communication or talking about risks with the patient. Patients' influence
      is insufficient in Sweden].

PMID- 15146672
TI  - [A technique or a relation? Critical factors in psychotherapy].

PMID- 15146673
TI  - [Alarmingly low quality of kindergartens--a new governmental investigation is
      necessary].

PMID- 15146674
TI  - [Hunting and the brain! Difficult decisions in connection with firearms permits].

PMID- 15146675
TI  - [New oral dehydration. Important that the new recommendations become widely
      known].

PMID- 15146676
TI  - [The syndrome "chronic carbon monoxide poisoning" could be turned down].

PMID- 15146677
TI  - [Objections against the discussion on amalgam and hypersensitivity].

PMID- 15146678
TI  - [Is there a test to indicate somatization?].

PMID- 15146679
TI  - [Mobile ultrasonography--examination of patients at home].

PMID- 15146680
TI  - [Drug industry and bribes].

PMID- 15146681
TI  - [The dilemma of prevention: Who is responsible, actually?].

PMID- 15146682
TI  - [Prevention of common diseases--strategic challenges].

PMID- 15146683
TI  - [Prognosis models: the effect of risk factor interventions].

PMID- 15146685
TI  - [Physical activity and chronic disease II. Type 2 diabetes, obesity and cancer].

PMID- 15146684
TI  - [Physical activity and chronic disease I. Heart disease and hypertension].

PMID- 15146688
TI  - [Obesity, the metabolic syndrome and cardiovascular disease].

PMID- 15146687
TI  - [Diet in the prevention of common diseases].

PMID- 15146689
TI  - [The Atkins diet. Status for documentation of the efficacy and safety].

PMID- 15146686
TI  - [Physical activity and chronic disease III. Musculoskeletal diseases and lung
      diseases].

PMID- 15146691
TI  - [Tobacco].

PMID- 15146690
TI  - [The work environment and common diseases].

PMID- 15146692
TI  - [Alcohol intake in Denmark--public health challenges and scientific questions].

PMID- 15146694
TI  - [Vitamin B12 deficiency and dementia].

PMID- 15146693
TI  - [Picture of the month: cardiovascular symptoms].

PMID- 15146695
TI  - [Treatment with ACE inhibitors in acute apoplexy].

PMID- 15146696
TI  - [Same drugs same names].

PMID- 15146697
TI  - [Treatment of arthrosis].

PMID- 15146698
TI  - [Flatulence in obesity].

PMID- 15146699
TI  - [Physicians and drug industry--open cooperation is the way forward].

PMID- 15146700
TI  - 9-10 months out. Loans, leases, and credentialing.

PMID- 15146701
TI  - How secure is your Social Security blanket?

PMID- 15146702
TI  - Caring for Latino patients.

PMID- 15146703
TI  - Who's to blame?

PMID- 15146704
TI  - No coding, no insurers--no kidding.

PMID- 15146706
TI  - How to traffic phone calls.

PMID- 15146705
TI  - How to spot a phony health plan.

PMID- 15146707
TI  - The risks of being a "patient advocate".

PMID- 15146708
TI  - My practice in paradise.

PMID- 15146709
TI  - Wall Street readies for an Atkins feast.

PMID- 15146710
TI  - One family's cause may cure a disease.

PMID- 15146712
TI  - Is nanotech ready for its close-up?

PMID- 15146711
TI  - Prioritizing the world's to-do list.

PMID- 15146714
TI  - Compensation monitor. Pharmacy directors see healthy increase in pay in 2003.

PMID- 15146713
TI  - $50 M for drug comparisons could produce valuable results.

PMID- 15146715
TI  - There's no such thing as 'futile care theory'.

PMID- 15146716
TI  - Do we really have best health care in the world?

PMID- 15146717
TI  - Plans go directly to patients, describing treatment options.

PMID- 15146719
TI  - Medical directors find themselves working more closely with payers.

PMID- 15146718
TI  - What's past is prologue? Don't bet on it. Interview by Patrick Mullen.

PMID- 15146720
TI  - Statin therapy: more than meets the eye?

PMID- 15146721
TI  - Transdermal patches are more than skin deep.

PMID- 15146722
TI  - Managed care outlook. Health savings accounts develop the mystique of a winning
      product.

PMID- 15146723
TI  - EPA's new focus: healthcare compliance.

PMID- 15146724
TI  - Commit yourself to lifelong learning. What you learned in school is not enough to
      carry you throughout your career.

PMID- 15146725
TI  - Managing the revenue cycle effectively: success factors from the field.

PMID- 15146726
TI  - "Good to great" in healthcare: how some organizations are elevating their
      performance.

PMID- 15146727
TI  - Certifying financials. Nonprofits should consider authenticating financial
      statements.

PMID- 15146728
TI  - Corporate citizenship. Corporations react responsibly to the larger needs of
      their communities.

PMID- 15146729
TI  - Physicians and capital purchases. Involving physicians in purchasing decisions
      can improve patient care and staff collaboration.

PMID- 15146731
TI  - Applying for-profit governance reforms. Is your healthcare organization prepared
      to comply?

PMID- 15146730
TI  - Patient-friendly billing. High-quality service doesn't stop when patients leave
      the hospital.

PMID- 15146732
TI  - Collaboration is the key. Network emphasizes cooperative planning.

PMID- 15146733
TI  - Boulders in the rock pile. Several significant issues will drive health policy in
      2004 and just beyond.

PMID- 15146734
TI  - Developing diverse experience. Going beyond your job description is key to career
      growth and development.

PMID- 15146735
TI  - Oil and wasser.
AB  - It was supposed to be an amicable "merger of equals," an example of European
      togetherness, a synergistic deal that would create the world's second-largest
      consumer foods company out of two former competitors. But the marriage of
      entrepreneurial powerhouse Royal Biscuit and the conservative, family-owned
      Edeling GmbH is beginning to look overly ambitious. Integration planning is way
      behind schedule. Investors seem wary. But for Royal Biscuit HR head Michael
      Brighton, the most immediate problem is that he can't get his German counterpart,
      Dieter Wallach, to collaborate on a workable leadership development plan for the
      merged company's executives. And stockholders have been promised details of the
      new organizational structure, including a precise timetable, in less than a
      month. The CEO of the British company--and of the postmerger Royal Edeling--is
      furious. It's partly a culture clash, but the problems may run deeper than that.
      The press is harping on details that counter the official merger-of-equals line.
      For instance, seven of the ten seats on the new company's management board will
      be held by Royal Biscuit executives. Will the clash of cultures undermine this
      cross-border merger? Commenting on the fictional case study are Robert F. Bruner,
      the executive director of the Batten-Institute at the University of Virginia's
      Darden Graduate School of Business Administration in Charlottesville; Leda
      Cosmides and John Tooby, the codirectors of the Center for Evolutionary
      Psychology at the University of California, Santa Barbara; Michael Pragnell, the
      CEO and director of the board for the agribusiness firm Syngenta, based in Basel,
      Switzerland; and David Schweiger, the president of the Columbia, South Carolina-
      based management consulting firm Schweiger and Associates.

PMID- 15146738
TI  - Learning to lead at Toyota.
AB  - Many companies have tried to copy Toyota's famous production system--but without
      success. Why? Part of the reason, says the author, is that imitators fail to
      recognize the underlying principles of the Toyota Production System (TPS),
      focusing instead on specific tools and practices. This article tells the other
      part of the story. Building on a previous HBR article, "Decoding the DNA of the
      Toyota Production System," Spear explains how Toyota inculcates managers with TPS
      principles. He describes the training of a star recruit--a talented young
      American destined for a high-level position at one of Toyota's U.S. plants. Rich
      in detail, the story offers four basic lessons for any company wishing to train
      its managers to apply Toyota's system: There's no substitute for direct
      observation. Toyota employees are encouraged to observe failures as they occur-
      for example, by sitting next to a machine on the assembly line and waiting and
      watching for any problems. Proposed changes should always be structured as
      experiments. Employees embed explicit and testable assumptions in the analysis of
      their work. That allows them to examine the gaps between predicted and actual
      results. Workers and managers should experiment as frequently as possible. The
      company teaches employees at all levels to achieve continuous improvement through
      quick, simple experiments rather than through lengthy, complex ones. Managers
      should coach, not fix. Toyota managers act as enablers, directing employees but
      not telling them where to find opportunities for improvements. Rather than
      undergo a brief period of cursory walk-throughs, orientations, and introductions
      as incoming fast-track executives at most companies might, the executive in this
      story learned TPS the long, hard way--by practicing it, which is how Toyota
      trains any new employee, regardless of rank or function.

PMID- 15146737
TI  - How to restore the fiduciary relationship. An interview with Eliot Spitzer.
      Interview by Louise O'Brien.
AB  - Eliot Spitzer's investigations into the mutual fund and investment-banking
      industries have made the New York State attorney general the de facto flag bearer
      of corporate reform. His exposure of conflicts of interest between investment
      bankers and research analyst in Wall Street firms led to the $1.4 billion global
      settlement between regulators and banking houses in 2003. In this interview,
      Spitzer describes the challenge of protecting public markets from conflicts of
      interest, paying particular attention to how such conflicts get institutionalized
      in an industry. "The cases that have gotten me and my fellow regulators most
      upset are the ones where we've seen senior management being tolerant of rank
      abuses," he says. "Because then you know that the entire structure is rotten." He
      also points the finger squarely at boards, maintaining that board members are
      drawn from pools of company and industry insiders. He cites "a void in values in
      a lot of boardrooms," holding up executive compensation as a powerful example.
      "Board compensation committees ... are self-selected and interwoven--it's a
      rigged marketplace." He continues, "It would be interesting to see what the world
      would look like if CEO pay packages had to be submitted to shareholder votes."
      Spitzer suggests that what's really needed is for all business leaders to
      reinstill throughout their organizations the critical notion of a fiduciary duty-
      whether it is to the shareholder or to the customer. Using the mutual fund
      industry as an example, he also contrasts the value of enforcement with that of
      regulation and articulates an important--and surprisingly limited--role for
      government in protecting free markets.

PMID- 15146736
TI  - Coaching the alpha male.
AB  - Highly intelligent, confident, and successful, alpha males represent about 70% of
      all senior executives. Natural leaders, they willingly take on levels of
      responsibility most rational people would find overwhelming. But many of their
      quintessential strengths can also make alphas difficult to work with. Their self
      confidence can appear domineering. Their high expectations can make them
      excessively critical. Their unemotional style can keep them from inspiring their
      teams. That's why alphas need coaching to broaden their interpersonal tool kits
      while preserving their strengths. Drawing from their experience coaching more
      than 1,000 senior executives, the authors outline an approach tailored
      specifically for the alpha. Coaches get the alpha's attention by inundating him
      with data from 360-degree feedback presented in ways he will find compelling-
      both hard-boiled metrics and vivid verbatim comments from colleagues about his
      strengths and weaknesses. A 360-degree assessment is a wake-up call for most
      alphas, providing undeniable proof that their behavior doesn't work nearly as
      well as they think it does. That paves the way for a genuine commitment to
      change. In order to change, the alpha must venture into unfamiliar--and often
      uncomfortable--psychological territory. He must admit vulnerability, accept
      accountability not just for his own work for others', connect with his underlying
      emotions, learn to motivate through a balance of criticism and validation, and
      become aware of unproductive behavior patterns. The goal of executive coaching is
      not simply to treat the alpha as an individual problem but to improve the entire
      team dynamic. Initial success creates an incentive to persevere, and the virtuous
      cycle reverberates throughout the entire organization.

PMID- 15146739
TI  - The risky business of hiring stars.
AB  - With the battle for the best and brightest people heating up again, you're most
      likely out there looking for first-rate talent in the ranks of your competitors.
      Chances are, you're sold on the idea of recruiting from outside your
      organization, since developing people within the firm takes time and money. But
      the authors, who have tracked the careers of high-flying CEOs, researchers,
      software developers, and leading professionals, argue that top performers quickly
      fade after leaving one company for another. To study this phenomenon in greater
      detail, the authors analyzed the ups and downs of more than 1,000 star stock
      analysts, a well-defined group for which there are abundant data. The results
      were striking. After a star moves, not only does her performance plunge, but so
      does the effectiveness of the group she joins--and the market value of her new
      company. Moreover, transplanted stars don't stay with their new organizations for
      long, despite the astronomical salaries firms pay to lure them from rivals. Most
      companies that hire stars overlook the fact that an executive's performance is
      not entirely transferable because his personal competencies inevitably include
      company-specific skills. When the star leaves the old company for the new, he
      cannot take with him many of the resources that contributed to his achievements.
      As a result, he is unable to repeat his performance in another company--at least
      not until he learns to work the new system, which could take years. The authors
      conclude that companies cannot gain a competitive advantage or successfully grow
      by hiring stars from outside. Instead, they should focus on cultivating talent
      from within and do everything possible to retain the stars they create. Firms
      shouldn't fight the star wars, because winning could be the worst thing that
      happens to them.

PMID- 15146740
TI  - Building better boards.
AB  - Companies facing new requirements for governance are scrambling to buttress
      financial-reporting systems, overhaul board structures--whatever it takes to
      comply. But there are limits to how much good governance can be imposed from the
      outside. Boards know what they ought to be: seats of challenge and inquiry that
      add value without meddling and make CEOs more effective but not all-powerful. A
      board can reach that goal only if it functions as a high-performance team, one
      that is competent, coordinated, collegial, and focused on an unambiguous goal.
      Such entities don't just evolve; they must be constructed to an exacting
      blueprint--what the author calls board building. In this article, Nadler offers
      an agenda and a set of tools that boards can use to define and achieve their
      objectives. It's important for a board to conduct regular self-assessments and to
      pay attention to the results of those analyses. As a first step, the directors
      and the CEO should agree on which of the following common board models best fits
      the company: passive, certifying, engaged, intervening, or operating. The
      directors and the CEO should then analyze which business tasks are most important
      and allot sufficient time and resources to them. Next, the board should take
      inventory of each director's strengths to ensure that the group as a whole
      possesses the skills necessary to do its work. Directors must exert more
      influence over meeting agendas and make sure they have the right information at
      the right time and in the right format to perform their duties. Finally, the
      board needs to foster an engaged culture characterized by candor and a
      willingness to challenge. An ambitious board-building process, devised and
      endorsed both by directors and by management, can potentially turn a good board
      into a great one.

PMID- 15146741
TI  - Telling tales.
AB  - A carefully chosen story can help the leader of an organization translate an
      abstract concept into a meaningful mandate for employees. The key is to know
      which narrative strategies are right for what circumstances. Knowledge management
      expert Stephen Denning explains that, for optimal effect, form should follow
      function. Challenging one professional storyteller's view that more is better,
      Denning points out that it's not always desirable (or practical) to launch into
      an epic that's jam-packed with complex characters, cleverly placed plot points,
      an intricate rising action, and a neatly resolved denouement. True, if listeners
      have time and interest, a narrative-savvy leader can use a vividly rendered tale
      to promote communication between management and staff, for instance, or even to
      foster collaboration--especially when the story is emotionally moving. However,
      if the aim is to motivate people to act when they might not be inclined to do so,
      it's best to take an approach that's light on detail. Otherwise, the particulars
      can bog listeners down and prevent them from focusing on the message. Drawing on
      his experiences at the World Bank and observations made elsewhere, the author
      provides several dos and don'ts for organizational storytellers, along with
      examples of narratives that get results. The sidebar "A Storytelling Catalog"
      presents seven distinct types of stories, the situations in which they should be
      told, and tips on how to tell them. Many of these aren't even stories in the
      "well-told" sense--they run the rhetorical gamut from one-liners to full-blown
      speeches--but they succeed because they're tailored to fit the situation. So even
      though it's common in business to favor the analytical over the anecdotal,
      leaders with the strength to push past some initial skepticism about the
      enterprise of storytelling will find that the creative effort pays off.

PMID- 15146742
TI  - Can absence make a team grow stronger?
AB  - Some projects have such diverse requirements that they need a variety of
      specialists to work on them. But often the best-qualified specialists are
      scattered around the globe, perhaps at several companies. Remarkably, an
      extensive benchmarking study reveals, it isn't necessary to bring team members
      together to get their best work. In fact, they can be even more productive if
      they stay separated and do all their collaborating virtually. The scores of
      successful virtual teams the authors examined didn't have many of the
      psychological and practical obstacles that plagued their more traditional, face
      to-face counterparts. Team members felt freer to contribute--especially outside
      their established areas of expertise. The fact that such groups could not
      assemble easily actually made their projects go faster, as people did not wait
      for meetings to make decisions, and individuals, in the comfort of their own
      offices, had full access to their files and the complementary knowledge of their
      local colleagues. Reaping those advantages, though, demanded shrewd management of
      a virtual team's work processes and social dynamics. Rather than depend on
      videoconferencing or e-mail, which could be unwieldy or exclusionary, successful
      virtual teams made extensive use of sophisticated online team rooms, where
      everyone could easily see the state of the work in progress, talk about the work
      in ongoing threaded discussions, and be reminded of decisions, rationales, and
      commitments. Differences were most effectively hashed out in tele-conferences,
      which team leaders also used to foster group identity and solidarity. When
      carefully managed in this way, the clash of perspectives led not to acrimony but,
      rather, to fundamental solutions, turning distance and diversity into competitive
      advantage.

PMID- 15146743
TI  - Alternative energy sources.

PMID- 15146744
TI  - [Histologic and anatomic correlation of the infraorbital region].
AB  - The infra-orbital area has not been well studied although it represents an
      interesting area in plastic surgery because of its implication in malarplasty
      reduction or transplantation for facial tissue repair. This work comprises an
      anatomic dissection layer by layer and a histologic study describing the various
      structures of this area. It was performed on 10 heads taken from cadavers (mean
      age 70 years old). The anatomic and histologic study found four layers: a
      subcutaneous fat layer, a muscular layer, a deep fat layer and a deep muscular
      layer. The superficial fat layer constitutes the convexity of the cheek and can
      be removed in plastic surgery reduction or reconstituted after atrophy following
      nasolabial musculo cutaneous flaps.

PMID- 15146745
TI  - [Application of a new vascular injection technique in the study of the
      infratemporal region].
AB  - The infra-temporal region (ITR) is an anatomically rich region thanks to its
      arterial and venous divisions and large nerve crossroads. It is also, as
      described by Robert et al". in a publication about the ITR, (22) "the hidden face
      of the manductory apparatus. The ITR is therefore a passageway for a large number
      of anatomical elements and its complexity makes it a particularly delicate region
      for daily surgical practice. For these many reasons the anatomical study of the
      ITR, which has already been the origin of a number of works, seemed interesting
      to us, and more particularly combined with the use of an original injection
      material, Odongel. The injection of this material, in the arterial as well as the
      venous system, enabled us to improve our dissections thanks to its flexibility,
      elasticity, its case-of-use and its speed of preparation. The complexity and
      richness of the region meant that in order to study it anatomically we had to
      focus on a specific anatomical element for each dissection session, especially at
      the beginning. After having used traditional products such as resins (methyl
      methacrylate), latex and even the too rigid silicon elastomers, Odongel seemed
      interesting to us because it is very easier to use it. The purpose of this study
      was to prove that Odongel is an efficient material, working equally well for both
      the arterial and venous systems irrespective of the diameter of the vessels
      concerned. It can become an alternative to the other injection products in some
      situations. Finally, in the case of the ITR, an extension of the existing
      techniques used in anatomical studies coupled with an increase in anatomical
      precision could improve our knowledge of this zone and eventually facilitate
      certain surgical interventions.

PMID- 15146746
TI  - [Internal iliac artery: functional anastomosis value and pelvic surgery
      application].
AB  - The vascularization of the intra and extra pelvic organs of adults, children and
      neonates (male and female) is studied in 17 pelvis, in which the vascular system
      has been injected with colored Altufix p10 and gelatinous india ink. The pelvic
      region constitute a true vascular crossroad of two anastomotic networks, one
      arterial, originate from the visceral and parietal branches of iliac internal and
      external arteries, femoral and abdominal aorta by inferior mesenteric artery; the
      other one, which morphology is incompletely superposable in diameter. Each organ
      is tributary of characteristic vascular system from adventitious to mucosa with
      direct or recurrential manner between striated muscle fibers and mucosal layers.
      This duality of two systems, vascular and anastomotic provides the anatomic
      direction of vascular suppliance after troncular iliac artery binding and
      determines the vitality of the organ.

PMID- 15146747
TI  - [Molecular control of ventro-dorsal polarization of the spinal neural tube in
      vertebrates].
AB  - The embryonic neural tube gives rise to the whole central nervous system (CNS) in
      vertebrates. The establishment of a dorsoventral axis in the neural tube is one
      of the first step to achieve the polarisation observed in the adult CNS: the
      dorsal aspect of it receives sensory inputs from the periphery and in response,
      the ventral aspect sends signals by motor cells: the motor neurones. This
      polarization is induced early in embryonic development by the signals secreted by
      polarizing centres such as the roof plate and the floor plate (e.g. BMP and Sonic
      Hedgehog). Since the neuroepithelium is sensitive to these signals, these cells
      respond by expressing sets of transcription factors in specific domains.
      Different combinations of transcription factors create progenitor domains that
      eventually give rise to post-mitotic neurones of different subtype in the dorso
      ventral axis of the neural tube.

PMID- 15146748
TI  - The consumer-driven approach: defining and measuring success.
AB  - Employers' reluctance to implement consumer-driven health plans (CDHPs) is at
      least in part due to their not understanding how to define and measure the
      success of CDHPs. To assist employers, the authors define potential points of
      success for CDHPs in the areas of consumer engagement, consumer financial
      considerations and employee health and productivity. They then offer ways of
      measuring success in those areas, as well as in the area of employer cost
      control. By taking a carefully considered approach to the decision of whether to
      offer a CDHP, employers can grasp potential opportunities to control health care
      costs.

PMID- 15146750
TI  - Consumer-driven health plans: design features to promote quality improvement.
AB  - The most prevalent form of consumer-driven health plans (CDHPs) presents risks in
      terms of the cost, quality and appropriate use of health care. This article
      identifies those risks and shows employers how they can reduce them without
      compromising the overall cost-control potential of CDHPs. A good CDHP strategy
      should work on both the demand and supply sides of the market.

PMID- 15146749
TI  - Consumer-driven health care: the future is now.
AB  - Given that managed care seems to have run its course, employers are forced to
      deal with escalating health care costs by reducing benefits and lowering pay--or
      are they? Why not bring the power of the responsible, informed consumer to health
      care? Consumer-driven health care offers a new, economically rational direction
      that can simultaneously address the needs of both employers and employees. This
      article reviews the factors leading to the need for consumer-driven health care
      and describes the characteristics and benefits of its current and next
      generations of development.

PMID- 15146751
TI  - reDefined contribution health care.
AB  - To combat rising health care costs and a society increasingly unsatisfied with
      employer-sponsored health care services, reDefined Contribution Health Care
      suggests a process to create a more consumer-driven health care market. To create
      this value-sensitive market requires a planned, staged approach that will include
      immediate actions and work toward fundamental, long-term changes.

PMID- 15146752
TI  - Engaging employees in health care can contain costs and improve quality.
AB  - Employers need to do much more to change some of the deep-seated employee
      attitudes and behaviors that are driving health care costs. This article debunks
      common employer misconceptions about employees' attitudes and behaviors with
      regard to health care. It then discusses the results employers can obtain by
      taking specific initiatives that provide employees with the motivation and
      resources they need to effectively manage health risks and make informed health
      care decisions.

PMID- 15146753
TI  - Consumer-driven health care: tangible employer actions.
AB  - In response to double-digit health care cost increases, leading employers are
      aiming aggressive strategies at changing participant and provider behaviors-
      strategies that go well beyond the narrow idea of a new cost-sharing design. This
      article describes the elements of a comprehensive consumer-driven health care
      strategy and provides examples of tangible consumer-driven health care
      initiatives in the areas of design, pricing, contracting, support and public
      policy.

PMID- 15146754
TI  - Defined contribution health plan to consumer driven health benefits: evolution
      and experience.
AB  - Today, the idea of placing more choice on employees "consuming" health care and
      giving them more responsibility and incentive to control health care costs and
      utilization is alive and thriving in the form of consumer-driven health care.
      This article examines the evolution of consumer-driven health benefits--including
      the experience of the first generation of "defined contribution" health care
      participants (i.e., retirees) and the results of different approaches employers
      have taken to early consumer-driven plan designs. The author then describes
      what's needed to answer the question: "Can consumer-driven health care control
      health cost?"

PMID- 15146755
TI  - Article really helped.

PMID- 15146756
TI  - Pediatricians can help, too.

PMID- 15146757
TI  - Cover bariatric surgery.

PMID- 15146758
TI  - Ask the patients.

PMID- 15146760
TI  - Fraud crackdown.

PMID- 15146759
TI  - Big 'R' or little 'r'.

PMID- 15146761
TI  - Future fears.

PMID- 15146762
TI  - Consumers' choice.

PMID- 15146763
TI  - Mad cow mania.

PMID- 15146764
TI  - Access, attitudes, and concerns of physicians and patients toward e-mail use in
      health-related communication.
AB  - The Internet is likely to play a key role in future health care-related
      communication. The challenge for health care institutions is to determine how to
      use this technology most effectively without disturbing the delicate physician
      patient relationship. As the first step to implementing the use of this
      technology, we explored the access, attitudes, and concerns both of physicians
      and patients regarding e-mail use for health care-related communication. At The
      University of Texas Medical Branch at Galveston, we administered a questionnaire
      survey to faculty and residents in the Internal Medicine and Pediatrics
      departments and to the patients seen in the resident clinics. The results
      indicate that only a select group of physicians and patients might be ready to
      use e-mail for health care reasons. Most patients did not have access to the
      Internet and had no experience using e-mail. Though all physicians use e-mail,
      they were concerned about using it for health-related communication.

PMID- 15146765
TI  - TSBME serves physicians, public.

PMID- 15146766
TI  - An opposing view of Proposition 12.

PMID- 15146767
TI  - Returning to the well.

PMID- 15146769
TI  - The baby blues.

PMID- 15146768
TI  - Doctors as cops.

PMID- 15146770
TI  - In their laps.

PMID- 15146771
TI  - Worth the cost?

PMID- 15146772
TI  - Too many edits.

PMID- 15146773
TI  - Predicting risk for disciplinary action by a state medical board.
AB  - Disciplinary actions taken against physicians in the United States have been
      increasing over the last decade, yet the factors that place physicians at risk
      have not been well identified. The objective of this study is to identify
      predictors of physician disciplinary action. This case-control study used data
      from the Texas State Board of Medical Examiners from January 1989 through
      December 1998. Characteristics of disciplined physicians and predictors of
      disciplinary action for all violations and by type of violation were the main
      outcome descriptors. Years in practice, black physicians, and osteopathic
      graduates were positive predictors for disciplinary action. In contrast, female
      physicians, international medical graduates, and Hispanic and Asian physicians
      were less likely to receive disciplinary action compared with male, US
      allopathic, and white physicians, respectively. Most specialists, except
      psychiatrists and obstetrician-gynecologists, were less likely to be disciplined
      than were family practitioners, whereas general practitioners were more likely to
      be disciplined. More studies are needed to corroborate these findings.

PMID- 15146775
TI  - Let spouses eat, too.

PMID- 15146774
TI  - Reverse the TWCC actions.

PMID- 15146776
TI  - Being proactive, not interventional or reactive.

PMID- 15146777
TI  - How Medicare reform affects you.

PMID- 15146778
TI  - Just say no.

PMID- 15146779
TI  - Good-bye, Robin Hood?

PMID- 15146780
TI  - A thankless job. Interview by Ken Ortolon.

PMID- 15146781
TI  - October surprise.

PMID- 15146782
TI  - Prevention of relapse to addiction: information for the practitioner.
AB  - The purposes of this review are to convey the current distinction between
      pathological drug dependence and voluntary drug abuse; to provide an overview of
      the anatomy and biochemistry of dependence; to discuss the rationale for
      attempting to prevent relapse by using therapeutic agents; and to describe
      effective agents that reduce relapse in alcohol- and opioid-dependent people.
      Drug dependence (formerly called "addiction") has as its essential characteristic
      "impaired control over use of the drug." Impaired control occurs when pathways
      are sensitized within the emotional brain, (usually) in genetically predisposed
      individuals. At the nerve cell level, impaired control occurs because of a type
      of neural adaptation (change in synaptic plasticity) within the pathway's nerve
      cells that alters their chemistry. Relapse in alcohol-dependent patients can be
      prevented by any of several agents that reduce craving for alcohol: naltrexone
      (ReVia), ondansetron (Zofran), and acamprosate (Campral, not yet available in the
      United States). Relapse in opioid-dependent patients can be prevented by the full
      agonists methadone and L-alpha-acetyl-methadol (LAAM) and the partial opioid
      agonist buprenorphine (Subutex and Suboxone). No other universally effective anti
      relapse medications exist for other chemical dependencies.

PMID- 15146784
TI  - [New diagnostic procedures in gastroesophageal reflux disease: from the Bernstein
      test to impedance].

PMID- 15146783
TI  - [Gastroesophageal reflux disease: defense mechanisms].

PMID- 15146785
TI  - [Reflux disease: a motor dysfunction?].

PMID- 15146786
TI  - GERD pathophysiology: the importance of acid control.
AB  - The optimal acute therapy for reflux disease is estimated and initiated on the
      basis of the patient's history. Endoscopy is initially warranted if there is
      significant doubt regarding the diagnosis of GERD or if the patient relays alarm
      symptoms suggesting more ominous diagnoses (dysphagia, bleeding, weight loss,
      odynophagia). Depending on the initial therapy rendered, medical therapy is then
      adjusted in a step up or step down fashion to ascertain the least potent
      effective regimen according to the scale of potency in table 1. Once identified,
      the optimal acute therapy should be maintained for at least 8 weeks. If even the
      most potent medical therapy still results in a poor response, further evaluation
      should be undertaken as indicated. On the other hand, if acute medical therapy
      alleviates symptoms, the patient should then be given a trial off of medication.
      The need for maintenance medical therapy is determined by the rapidity of
      recurrence; recurrent symptoms in less than 3 months suggest disease best managed
      with continuous therapy while remissions in excess of 3 months can be adequately
      managed by repeated courses of acute therapy as necessary. The 3 month figure is
      derived from observations of patients randomized to placebo in maintenance trials
      of proton pump inhibitors; if recurrence was going to occur within a year, it
      invariably occurred within the first 3 months. It is this author's opinion that
      patients who requires continuous maintenance therapy should have an endoscopy to
      rule out Barrett's metaplasia and, in particular, dysplasia. Patients on
      effective maintenance therapy may opt to have elective antireflux surgery after a
      thorough discussion of the associated risks and benefits.

PMID- 15146787
TI  - [Clinical significance of metaplasia-dysplasia].

PMID- 15146788
TI  - [Advances in pharmacologic treatment of gastroesophageal reflux disease].

PMID- 15146789
TI  - New endoscopic treatments for gastroesophageal reflux.

PMID- 15146790
TI  - [Laparoscopic fundoplication. Ideal standard?].

PMID- 15146791
TI  - Conferencia magistral oropharyngeal disorders: diagnosis and treatment.
AB  - In summary, the management of oropharyngeal dysphagia often involves a
      polydisciplinary evaluation, the aims of which are to identify and characterize
      oropharyngeal dysphagia as well as identify the underlying cause whenever
      possible. A specific diagnosis of the underlying cause of neurogenic dysphagia is
      rarely made on the basis of videoradiographic or manometric observations because
      observed patterns of oral, laryngeal, pharyngeal and cricopharyngeal dysfunction
      can exist in a range of neurogenic disorders. Finding the underlying cause of
      oropharyngeal dysphagia often requires the clinical team to think broadly, owing
      to the wide array of diagnostic possibilities. Special emphasis should be placed
      on detecting treatable underlying systemic conditions such as thyrotoxicosis,
      myopathy, myasthenia, and neoplasms. While seeking evidence for a systemic
      disorder, the second aim of clinical evaluation is to identify surgically (or
      endoscopically) treatable structural abnormalities. Careful radiographic and/or
      endoscopic examination of the oropharynx and proximal esophagus is aimed at
      detecting signs of neoplasm, infection, strictures, or diverticuli, each of which
      implies a specific therapy. After important etiologic abnormalities have been
      sought, functional abnormalities of the oropharyngeal swallow should be defined.
      Characterization of the temporal disruption of the swallow coordination and
      identification of the underlying mechanism leading to that dysfunction requires a
      videofluoroscopic or cineradiographic examination. In some instances, especially
      with suspected UES dysfunction, concurrent use of pharyngeal manometry with
      videofluoroscopy can allow further delineation of the underlying pathology and
      direct treatment. From this point onwards, management decisions will be
      applicable to those patients in whom a structural surgically treatable
      abnormality has been excluded. When considering further treatment strategies, the
      clinician must first establish whether institution of non-oral (e.g. gastrostomy)
      feeding is indicated. This will depend on establishing the likelihood that the
      patient will be able to sustain adequate nutrition safely via the oral route and
      on the unproven, but reasonable, premise that non-oral feeding is likely to
      reduce the risk of aspiration pneumonia. This decision is made in conjunction
      with the speech language pathologist who can, on the basis of videofluoroscopic
      analysis of therapeutic maneuvers, estimate the likelihood that such maneuvers
      will reduce the risks of oral feeding and enhance the efficiency of the swallow.
      The natural history and prognosis of the underlying cause for dysphagia, as well
      as the patient's cognitive ability, will also influence the choice between oral
      and non-oral feeding. Introduction of appropriate dietary modification and
      specific swallow therapy by the speech language pathologist is appropriate at
      this point. The choices among therapies will be directed by the videofluoroscopic
      findings and the individual patient's ability to comprehend and cooperate with
      the various strategies. This process will frequently involve a subsequent
      videofluoroscopic examination to assess progress and the advisability of ongoing
      swallow therapy and ascertain whether alternatives should be considered. The
      place of cricopharyngeal myotomy, and other procedures such as laryngeal
      suspension, in this class of patient remains controversial. The clinician can
      predict an overall response rate from myotomy of around 60%, but, at present,
      cannot predict the likelihood of response in an individual patient with
      certainty. Until further well designed studies in clearly defined subsets of
      patients are conducted, the decision about myotomy will remain empirical after
      informing the patient of the risk and possible, but unproven, benefit.

PMID- 15146792
TI  - [Barrett's esophagus. Metaplasia-dysplasia-cancer: inexorable change?].

PMID- 15146793
TI  - EUS in the evaluation of Barrett's esophagus. Is it necessary?

PMID- 15146794
TI  - Barrett's esophagus--the future tools for diagnosis: biological markers and
      cellular alternations.

PMID- 15146795
TI  - Barrett's esophagus--mucosectomy and endoscopic ablation.

PMID- 15146796
TI  - Physiology and pathophysiology of gastroduodenal secretion.

PMID- 15146797
TI  - Pathogenesis of H. pylory-associated duodenal ulcer disease.

PMID- 15146798
TI  - Gastroduodenal pathophysiology of NSAIDS. Short summaries of the slides.
AB  - We need to learn a lot more about the pathophysiology of NSAIDs, especially COX
      2, which at present are the drugs of choice.

PMID- 15146799
TI  - NSAID and PUD complications.

PMID- 15146800
TI  - [Helicobacter pylori and peptic ulcer hemorrhage].

PMID- 15146801
TI  - New and old methods for endoscopic control of nonvariceal upper gastrointestinal
      bleeding.
AB  - Candidates for endoscopic therapy of nonvariceal upper gastrointestinal bleeding
      include patients with bleeding ulcers, Mallory-Weiss tears, angiodysplasia, and
      Dieulafoy or other lesions with active bleeding, non-bleeding visible vessel, or
      adherent clot. Continuous infusion of intravenous proton pump inhibitors lowers
      rebleeding risk after endoscopic therapy. Of standard methods, a combination of
      epinephrine injection with thermal coagulation (bipolar or heater probe) has been
      shown to be optimal, with lower rebleeding rates (5-10%) than for either method
      alone. Endoscopic clipping is an appealing technique, but comparative data with
      other methods are limited and conflicting. Band ligation is also suitable for
      many non-ulcer lesions without a firm base. Argon plasma coagulation is most
      useful for lesions with a large surface area such as watermelon stomach, but of
      uncertain advantage for other nonvariceal bleeding lesions. Regardless of method
      used, technical expertise plays a role in the outcomes of therapy. Of future
      interest are techniques to image beneath the surface and predict rebleeding risk,
      and improved methods of mechanical hemostasis.

PMID- 15146802
TI  - [Gastric neoplasia. Metaplasia, atrophy, and dysplasia. Clinical course times].

PMID- 15146803
TI  - Early gastric cancer.

PMID- 15146804
TI  - EUS for the evaluation of subepithelial tumors and thickened gastric folds.
AB  - Endoscopic ultrasound examination is extremely useful in clarifying potential
      etiologies of previously enigmatic subepithelial lesions and thick-fold
      gastropathies. In cases in which the endosonographic appearance is not
      diagnostic, EUS may aid in obtaining a definitive tissue diagnosis via EUS-guided
      needle biopsy or by establishing suitability for endoscopic mucosal resection.
      The evaluation of subepithelial tumors and thickened folds represents an ideal
      starting point for the novice endosonographer as adequate interpretation is not
      dependent upon a firm understanding of extraintestinal anatomy.

PMID- 15146805
TI  - Conferencia magistral gastric MALT-lymphoma.

PMID- 15146806
TI  - [Duodenitis. Clinical significance].

PMID- 15146807
TI  - [Functional dyspepsia].

PMID- 15146808
TI  - [Why are population studies so important?].

PMID- 15146809
TI  - [Epidemiological research during the last 40 years. Population studies in
      Glostrup--the Research Center for Disease Prevention--the Research Center for
      Prevention and Health].

PMID- 15146810
TI  - [The contribution of population studies to research of public health problems
      with focus on Danish cohorts].

PMID- 15146811
TI  - [Cohort studies for beginners. An introduction to cohort design and basal
      concepts].

PMID- 15146812
TI  - [Project Metropolit. A status report].

PMID- 15146813
TI  - [The National Institute of Public Health's program for health and morbidity
      surveys].

PMID- 15146814
TI  - [DANCOS--a registry-based follow-up of Danish national health surveys].

PMID- 15146815
TI  - [The Copenhagen Male Study].

PMID- 15146816
TI  - [The Odense Androgen Study].

PMID- 15146817
TI  - [The Danish Nurse Cohort Study 1993-2003].

PMID- 15146818
TI  - [The role of Danish Psychiatric Central Research Registry in the research of
      widespread mental disorders].

PMID- 15146819
TI  - [From cancer statistics to the Cancer Registry].

PMID- 15146820
TI  - [Pronounced differences in the estimation of breast cancer mortality in
      connection with hormone replacement therapy and mammographic screening].

PMID- 15146821
TI  - [Cancer and HRT--"now when the dust has settled"].

PMID- 15146822
TI  - [Surgical treatment of Crohn disease].

PMID- 15146823
TI  - [Abstracts of the reports of All-Russian Scientific Conference: Reactivity and
      Plasticity of Histological Structures in Normal, Experimental and Pathological
      Conditions. Orenburg, November 18-20, 2003. Dedicated to the memory of the
      Corresponding Member of USSR Academy of Medical Sciences Professor F M
      Lazarenko].

PMID- 15146824
TI  - Computer power tapped for AIDS.

PMID- 15146825
TI  - Clinton-brokered AIDS drug-price agreement to benefit millions.

PMID- 15146826
TI  - AIDS-prevention products focus of global conference.

PMID- 15146827
TI  - Prevention. Students lose battle against abstinence-only sex education.

PMID- 15146828
TI  - Substandard care. Hospital's revocation of HIV specialist's license upheld.

PMID- 15146829
TI  - Conference. HIV/AIDS community gathers for updates on epidemic.

PMID- 15146831
TI  - Rate reductions to Medicaid providers halted in California.

PMID- 15146830
TI  - One-third of people on ADAP waiting list from Colorado.

PMID- 15146832
TI  - Disparate sentencing legal to protect youth from HIV.

PMID- 15146834
TI  - Probation revocation upheld for failing to get HIV test.

PMID- 15146833
TI  - Fluid exchange necessary to court-order AIDS testing.

PMID- 15146835
TI  - HIV testing order thrown out in wrongful arrest case.

PMID- 15146836
TI  - HIPAA. Courts protect sensitive medical records from DOJ.

PMID- 15146837
TI  - Testing errors. Maryland officials order hospital to fix HIV/AIDS testing lab.

PMID- 15146838
TI  - [Osteomyelitis after endoprostheses].
AB  - Today over 170,000 total hip arthroplasties and about 70,000 total knee
      arthroplasties are performed in Germany. An overall infection rate of 0.5-1.4% is
      reported in the literature. This means that 800-1700 infections after total hip
      arthroplasty and 300-850 infections after total knee arthroplasty can occur. The
      surgical treatment of early or late infections after arthroplasty of the hip or
      knee needs different intervention. Depending on when the infection develops, a
      simple Debridement, an allinone exchange arthroplasty, or the explantation of the
      endoprosthesis with implantation of a spacer followed by the reimplantation of a
      new prosthesis must be performed. The first hint of postoperative infection is
      the increase of the C-reactive protein. By correct treatment of the postoperative
      wound the first sign of an infection can be detected early.

PMID- 15146839
TI  - Microbioreactor arrays with parametric control for high-throughput
      experimentation.
AB  - A scalable array technology for parametric control of high-throughput cell
      cultivations is demonstrated. The technology makes use of commercial printed
      circuit board (PCB) technology, integrated circuit sensors, and an
      electrochemical gas generation system. We present results for an array of eight
      250 microl microbioreactors. Each bioreactor contains an independently
      addressable suite that provides closed-loop temperature control, generates feed
      gas electrochemically, and continuously monitors optical density. The PCB
      technology allows for the assembly of additional off-the-shelf components into
      the microbioreactor array; we demonstrate the use of a commercial ISFET chip to
      continuously monitor culture pH. The electrochemical dosing system provides a
      powerful paradigm for reproducible gas delivery to high-density arrays of
      microreactors. Growth data are presented for Escherichia coli cultured in the
      array with varying microaerobic conditions using electrochemically generated
      oxygen. Additionally, we present data on carbon dioxide generation for pH dosing.

PMID- 15146840
TI  - [Historical study of the moth repellent, "Fujisawa Camphor" (3) An exposition as
      an advertisement media].
AB  - Newspaper advertisements were the predominant medium in informing people about
      new products midway through the Meiji Era. Subscribers to these newspapers,
      however, were still limited. At the time, expositions were wildly popular.
      Seizing the opportunity , in 1903 Fujisawa promoted his "Fujisawa Camphor"
      through aggressive advertising at the 5th Domestic Industrial Exposition in
      Osaka. The advertising proved to be a success, as Fujisawa took 2nd Prize of the
      exposition.

PMID- 15146841
TI  - [Characteristics of pharmaceuticals in "Heji Jufang"].
AB  - Dosage forms, methods of preparation, and methods of taking drugs for formulas
      described in "Heji Jufang" were investigated and the following results were
      obtained.1) Powders and pills (processed medicines), which are dosage forms
      seldom used in conventional traditional Chinese medicine, are often seen in "Heji
      Jufang". On the other hand, the fact that decoction (non-processed medicines),
      which is the principal dosage form in traditional Chinese medicine, seldom
      appears became apparent. In addition, a method of taking the drug by boiling down
      the powder was frequently seen.2) When decoction formulas are described in "Heji
      Jufang", the herbal medicines are often classified into two sections, a preceding
      section and latter one. The herbal medicines as prepared at a pharmacy are listed
      in the preceding section, while "standard household items" to add during home
      preparation are assumed to be described in the latter section.3) In "Heji
      Jufang", there is a rare method of taking drugs where boiling water is poured on
      powder consisting of aromatic herbal medicine before use. Many of these formulas
      are found in "Yinshan Zhengyao", which contains food and drink of the Arab
      region.4) "Heji Jufang" contains confections prepared with honey and powders of
      crude drugs. This dosage form is often seen in Indian and Arab medicine and was
      rarely seen in medical books before "Heji Jufang" in China.5) Thus, results 1-4
      suggest that "Heji Jufang" was published in accordance with the development of
      processed medicines. It is believed that Arab medicine influenced the development
      of processed medicines in China.

PMID- 15146842
TI  - Meta-analyses and megatrials: neither is the infallible, universal standard.

PMID- 15146843
TI  - [Particular combination of two crude drugs used in six stages in Shang-Han-Lun].
AB  - In the "Shang-Han-Lun", a famous old formulary in traditional Chinese medicine,
      the exogennous diseases are classified into six stages of syndromes according to
      the progress of the illness in general terms for tai-yang, shao-yang, yang-ming,
      tai-yin, shao-yin and jeu-yin stages. The frequency of particular combinations of
      two crude drugs used in the six stages of diseases was examined to obtain the
      guidance in the preparation of new and appropriate formulations for modern
      medical treatments. The best pairs frequently mentioned in the tai-yang and yang
      ming stages were the pair of Glycyrrhizae Preparata Radix (Sha-kanzo in Japanese)
      and Cinnamomi Ramulus (Keishi in Japanese), and Rhei Rhizoma and Natrii Sulfas,
      respectively. The characteristic combinations in the shao-yang stage were the
      pairs containing Scutellariae Radix and Pinelliae Tuber, which is contained in te
      formulation Xiao-Chai-Hu-Tang (Sho-saiko-to in Japanese). The pair of
      Glycyrrhizae Preparata and Radix Paeoniae Radices is the characteristic in the
      tai-yin stage, which is used for the treatment of muscular spasms and pain. The
      pair of Aconiti Preparata and Zingiberis Rhizoma is used for the treatment of
      diarrhea with cold pain in the shao-yin and jue-jin stages. The present results
      of these crude drugs of pairings will be useful to create a new formulation of
      crude drugs for modern medical treatment.

PMID- 15146844
TI  - [An etymology of pharmacy in the Western languages].
AB  - An etymological and semantic history of the terms of various pharmaceutical
      retailers in the West in presented. Apothecary is a combination of IE * apo-
      (separate) and * dhe (to place) which gave rise to the Greek term apotheke, which
      originally meant a warehouse for food and wine. Pharmacy is a combination of the
      Greek term * pharama form IE * bher- (to charm, enchant) and -(a)-ko- resulting
      in * pharmako- (magic, charm, cure, potion, medicine) and in Latin pharmacie.
      Chemist's shop is the English version of an American drugstore. Further, such
      terms as dispensary, officinal and drug are etymologically discussed. Different
      usages in England and the U.S. of terms like shop and store are summarized.
      [Note:"IE" with asterisk stands for the Indo-European proto-languages which are
      the ancestors of most Western tongues.]

PMID- 15146845
TI  - End-of-life care varies significantly even among top hospitals.

PMID- 15146846
TI  - Misguided resistance to appropriate treatment for adolescent depression.

PMID- 15146847
TI  - Low health literacy is a major problem, reports says.

PMID- 15146848
TI  - Virtual colonoscopy isn't ready for widespread use, study says.

PMID- 15146849
TI  - Online calculator reduces nutrition-related pediatric adverse drug events.

PMID- 15146850
TI  - Who--or what--are the rats (and mice) in the laboratory.
AB  - This paper explores the many meanings attached to the designation, "the rodent in
      the laboratory" (rat or mouse). Generations of selective breeding have created
      these rodents. They now differ markedly from their wild progenitors, nonhuman
      animals associated with carrying all kinds of diseases. Through selective
      breeding, they have moved from the rats of the sewers to become standardized
      laboratory tools and (metaphorically) saviors of humans in the fight against
      disease. This paper sketches two intertwined strands of metaphors associated with
      laboratory rodents. The first focuses on the idea of medical/scientific progress;
      in this context, the paper looks at laboratory rodents often depicted (in
      advertising for laboratory products) as epitomizing medical triumph or serving as
      helpers or saviors. The second strand concerns the ambiguous status of the
      laboratory rodent who is both an animal (bites) and not an animal (data). The
      paper argues that, partly because of these ambiguous and multiple meanings, the
      rodent in the laboratory is doubly "othered"--first in the way that animals so
      often are made other to ourselves and then other in the relationship of the
      animal in the laboratory to other animals.

PMID- 15146851
TI  - Cruel choices: autonomy and critical care decision-making.
AB  - Although autonomy is clearly still the paradigm in bioethics, there is increasing
      concern over its value and feasibility. In agreeing with those concerns, I argue
      that autonomy is not just a status, but a skill, one that must be developed and
      maintained. I also argue that nearly all health-care interactions do anything but
      promote such decisional skills, since they rely upon assent, rather than upon
      genuinely autonomous consent. Thus, throughout most of their medical lives,
      patients are socialised to be heteronomous, rather than autonomous. Yet, at the
      worst possible time--critical care decision-making--when life and death
      consequences are attached to the choices, the paradigm shifts and real consent is
      sought, even demanded, thereby making an often traumatic situation even harder. I
      go on, though, to also reject paternalistic models of beneficence as an
      alternative. Rather, I conclude that the problem is so fundamental in healthcare
      that a genuine solution would require a radical restructuring. I recommend steps
      that can be taken in the interim to improve the situation and to move toward such
      a restructuring.

PMID- 15146852
TI  - Sharing death and dying: advance directives, autonomy and the family.
AB  - This paper critically examines the liberal model of decision making for the
      terminally ill and contrasts it with the familial model that can be found in some
      Asian cultures. The contrast between the two models shows that the liberal model
      is excessively patient-centered, and misconceives and marginalises the role of
      the family in the decision making process. The paper argues that the familial
      model is correct in conceiving the last journey of one's life as a sharing
      process rather than a process of exercising one's prior or counterfactual choice,
      and concludes by suggesting a policy framework for the practice of familialism
      that can answer the liberal challenge that familialism cannot safeguard the
      patient from abuse and neglect.

PMID- 15146853
TI  - Critical bioethics: beyond the social science critique of applied ethics.
AB  - This article attempts to show a way in which social science research can
      contribute in a meaningful and equitable way to philosophical bioethics. It
      builds on the social science critique of bioethics present in the work of authors
      such as Renee Fox, Barry Hoffmaster and Charles Bosk, proposing the
      characteristics of a critical bioethics that would take social science seriously.
      The social science critique claims that traditional philosophical bioethics gives
      a dominant role to idealised, rational thought, and tends to exclude social and
      cultural factors, relegating them to the status of irrelevancies. Another problem
      is they way in which bioethics assumes social reality divides down the same
      lines/categories as philosophical theories. Critical bioethics requires
      bioethicists to root their enquiries in empirical research, to challenge theories
      using evidence, to be reflexive and to be sceptical about the claims of other
      bioethicists, scientists and clinicians. The aim is to produce a rigorous
      normative analysis of lived moral experience.

PMID- 15146855
TI  - Bibliography. Current world literature. Genitourinary systems.

PMID- 15146854
TI  - Quantification of the proliferation index of human dermal fibroblast cultures
      with the ArrayScan high-content screening reader.
AB  - High-throughput cell-based assays are becoming a powerful approach in the drug
      discovery process. The ArrayScan high-content screening (HCS) reader is a
      cytometer based on a fully automated fluorescence microscope that is able to
      obtain quantitative information on the intensity and localization of fluorescence
      signals within single cells over a wide cell population. The aim of this work was
      to set up an automated HCS multiparameter analysis for the quantification of the
      in vitro proliferation index of normal human dermal fibroblast (NHDF) cultures.
      The authors stimulated starved NHDF with insulin-like growth factor-1, platelet
      derived growth factor, epidermal growth factor, fibroblast growth factor, or
      serum, and they quantified the proliferation index by measuring the expression of
      Ki-67 antigen, the incorporation of bromodeoxyuridine (BrdU), and the
      phosphorylation of the retinoblastoma protein (pRb). This approach also allowed
      quantification of the mitotic index by phospho-histone H3 staining and the
      percentage of cells in the S-phase by BrdU incorporation. The proliferation data
      from the ArrayScan assays were validated by comparison with a reference enzyme
      linked immunosorbent assay (ELISA) and by flow cytometry. The measured
      proliferation indices were highly reproducible in repeated measures and
      independent experiments. The authors therefore propose that the ArrayScan HCS
      system could be used for high-throughput multiparameter analysis and
      quantification of the proliferation of cellular cultures.

PMID- 15146856
TI  - Process analytical technology and ASTM Committee E55.

PMID- 15146857
TI  - Committee E55 on process analytical technology: a supplier's perspective.

PMID- 15146858
TI  - [Sonography].

PMID- 15146859
TI  - ["On the colored light of double stars and certain other stars of heaven" and
      what happened hence].
AB  - Christian Doppler, born 1853 as the second son of a stonemason-family in
      Salzburg, studied mathematics and physics and became Professor in Prague and in
      Vienna. In 1842 he described in a short theoretical study the relation of the
      waves of light of double stars and derived a simply formula and shows the
      deviation of the waves by the movement of the stars. In hard scientific
      discussions the correctness and the value of this simple formula was in doubt. In
      the zenith of his life and career he became Professor and Director of the new
      founded Institute of Physics of the University of Vienna. But although he was 49
      years old, his health was so bad and he retired. In the following year he died.
      About 100 years later, since 50 years, the principle he described becomes
      importance by the introduction of ultrasound, radar-technique, etc.

PMID- 15146860
TI  - Are cell phones safe? Questions remain.

PMID- 15146862
TI  - Cell Surface: From Molecules to Shape. Abstracts of a workshop. September 25-27,
      2003, Italy.

PMID- 15146861
TI  - [Detection by ultrasonic computed tomography].

PMID- 15146863
TI  - The truth about low-carb foods.

PMID- 15146864
TI  - US criticises Bulgarian nurses' conviction. Condemnation for death sentences met
      by protests in Libya.

PMID- 15146865
TI  - Central American trade pact may limit access to generics. Critics say agreement
      puts profits ahead of public health.

PMID- 15146866
TI  - Headaches that could spell trouble.

PMID- 15146867
TI  - Echinococcosis: transmission biology and epidemiology. Dedicated to the memory of
      Dr. Michael Gemmell.

PMID- 15146868
TI  - Nuts: a healthful handful?

PMID- 15146870
TI  - Japanese national universities are now 'incorporated'.

PMID- 15146871
TI  - 'Spinning in': a new concept for technology transfer?

PMID- 15146873
TI  - University entrepreneur initiatives on the rise.

PMID- 15146872
TI  - Killing two birds with one RKIP.
AB  - Analysis of metastatic prostate cancers has identified the Raf kinase inhibitory
      protein (RKIP) as a suppressor of metastases. Previous studies demonstrated that
      RKIP binds to Raf-1 and prevents the activation of the extracellular regulated
      kinase (ERK) cascade. New work shows that phosphorylation of RKIP by protein
      kinase C disassociates RKIP from Raf-1 and stimulates its binding to, and
      inhibition of G-protein-coupled receptor kinase 2 (GRK2). This switching enhances
      signaling by activation of the ERK pathway and by decreased receptor
      desensitization.

PMID- 15146874
TI  - Singapore trains biotech workforce abroad.

PMID- 15146875
TI  - [Specific immunotherapy. Hyposensitization with allergens].
AB  - Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan
      ges resulting in reduced allergic inflammatory reactions. SIT has long-term
      effects in mild forms of inhalant allergies and is effective even when standard
      pharmacotherapy fails. Moreover, the risk to develop additional allergic
      sensitizations and the development of asthma is significantly reduced in children
      with allergic rhinitis. SIT is the treatment of choice in patients with systemic
      reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT
      still have to be clarified, the most probable effect is a modulation of
      regulatory T cells associated with a switch of allergen-specific B-cells towards
      IgG4 production. The critical point to insure efficacy and safety is the
      selection of patients and allergens, task best performed by a specialist trained
      in allergology. Further details are available in the position papers of the
      German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und
      Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can
      be found at www.dgaki.de.

PMID- 15146877
TI  - Cumulative index, volumes 1-74.

PMID- 15146876
TI  - Company founders: voices of experience.

PMID- 15146878
TI  - [Type I and type IV sensitization to Asparagus officinalis].
AB  - Asparagus (Asparagus officinalis),a member of the Liliaceae family, is a popular
      vegetable, most commonly eaten in May. A 55-year-old cook presented with seasonal
      (always in May) recurrent dyshidrosiform hand eczema which prevented him from
      working. He also reported developing dyspnea and dysphagia after consuming
      asparagus. Diagnostic allergy testing revealed positive reactions against
      asparagus in prick-to-prick and epicutaneous patch tests.

PMID- 15146879
TI  - Bibliography. Current world literature. Pediatric asthma and development of
      atopy.

PMID- 15146881
TI  - Abstracts of the XII Biennial Meeting of the Society for Free Radical Research
      International. May 5-9, 2004, Buenos Aires, Argentina.

PMID- 15146880
TI  - Abstracts of the 3rd World Congress in Neurological Rehabilitation. April 5,
      2002, Venice, Italy.

PMID- 15146882
TI  - Abstracts of the 12th Association of European Psychiatrists Congress. Geneva,
      Switzerland, 14-18 April 2004.

PMID- 15146883
TI  - [The incompetent perforators in the development of varicose veins].
AB  - AIM: Does it make sense to dissect any incompetent perforator which is found with
      the color duplex sonography during the preoperative mapping of varicose veins?
      PATIENTS AND METHODS: 221 patients with recurrent varicose veins were examined by
      color duplex sonography for new transfascial insufficiencies. RESULTS: Among 371
      transfascial insufficiencies there were 61 (16.4%) incompetent perforators. 31
      isolated perforators (25 (9.4%) of 266 legs isolated perforators of the thigh,6
      (2.3%) isolated perforators of the calf) were exclusively responsible for the
      recurrence of varicose veins. 13 incompetent perforators of the calf were
      associated with additional transfascial insufficiencies,as well as superficial
      and in 3 cases even deep varicose veins, resulting at an advanced clinical stage
      (CEAP-classification C3-CS). CONCLUSION: The dissection of the thigh perforators
      and the rare isolated perforators of the calf may help to protect from possible
      and early recurrence.

PMID- 15146884
TI  - Eric W. Taylor, MB. Interview by Vicki Glaser.

PMID- 15146885
TI  - Nicotine: potentially a multifunctional carcinogen?

PMID- 15146886
TI  - [Bureau-Barriere syndrome of the hand. A case report on an unusual localization].
AB  - The Bureau-Barriere syndrome is described as an acral ulcer with mutilating
      osteolysis of the limbs that is nonfamiliar, non-sex-specific, induced by many
      factors, and elicited by sensory-trophic polyneuropathy. Often a bilateral
      location at the lower limb of male alcoholics has been described. We report about
      a 76-year-old diabetic women with unilateral mutilating acroosteolysis and
      ulceration of one finger and discuss the relevant clinical aspects of the Bureau
      Barriere syndrome.

PMID- 15146887
TI  - [The role of meta-analysis in assessing the treatment of advanced non-small cell
      lung cancer].
AB  - Meta-analysis is a statistical method allowing an evaluation of the direction and
      quantitative importance of a treatment effect observed in randomized trials which
      have tested the treatment but have not provided a definitive conclusion. In the
      present review, we discuss the methodology and the contribution of meta-analyses
      to the treatment of advanced-stage or metastatic non-small-cell lung cancer. In
      this area of cancerology, meta-analyses have provided determining information
      demonstrating the impact of chemotherapy on patient survival. They have also
      helped define a two-drug regimen based on cisplatin as the gold standard
      treatment for patients with a satisfactory general status. Recently, the meta
      analysis method was used to measure the influence of gemcitabin in combination
      with platinium salts and demonstrated a small but significant benefit in
      survival, confirming that gemcitabin remains the gold standard treatment in
      combination with cisplatin.

PMID- 15146889
TI  - NIH panel calls for limits on consulting.

PMID- 15146888
TI  - World Trade Center rescuers face lung distress.

PMID- 15146890
TI  - [Cutaneous necroses mainly on the extremities].

PMID- 15146892
TI  - Canada draws near to approving Africa drugs deal.

PMID- 15146891
TI  - WHO puts HIV/AIDS pandemic at top of its agenda.

PMID- 15146893
TI  - Pregnancy complications kill 70000 teenagers a year.

PMID- 15146894
TI  - Spanish HIV registry should be abolished, court rules.

PMID- 15146896
TI  - Bush accused of financially neglecting research. Below-inflation investment
      increases will rob USA of scientific dominance, claim experts.

PMID- 15146897
TI  - Create curb appeal.

PMID- 15146895
TI  - Response to "Breastfeeding, asthma, and atopic disease: an epidemiological review
      of the literature" by Oddy and Peat.

PMID- 15146898
TI  - D-amino acid homopiperazine amides: discovery of A-320436, a potent and selective
      non-imidazole histamine H(3)-receptor antagonist.
AB  - Structure-activity relationships of homopiperazine-containing alkoxybiaryl
      nitriles employing various D-amino acid moieties and their N-furanoyl analogues
      were undertaken. This led to A-320436, a potent and selective non-imidazole H(3)
      receptor antagonist possessing balanced affinity for both rat and human H(3)
      receptors. This compound was shown to demonstrate in vitro and in vivo functional
      antagonism and is non-neurotoxic at doses (i.p.) up to 163 mg/kg in a general
      observation test.

PMID- 15146899
TI  - Hemorrhagic complications of anticoagulant therapy in Chinese patients.
AB  - BACKGROUND: Oral anticoagulants have an expanding role in cardiovascular and
      thrombotic disorders. Few data are available describing their safety among
      Chinese patients. We aim to evaluate the incidence of major and minor bleeding
      complications among Chinese patients receiving long term anti coagulants in
      community practice. METHODS: A retrospective cohort study was undertaken in a
      regional hospital. All patients who were initiated on warfarin from January 1,
      1998 to December 31, 1998 were enrolled. Out-patient medical charts were reviewed
      for demographic data, clinical characteristics and adequacy of anticoagulation.
      Major and minor bleeding complications were documented. RESULTS: A total of 131
      patients were identified. The mean age was 67.8 (SD 11.9) years and 52.6% were
      women. The mean duration of follow-up was 2.2 years (SD 1.1). Major indications
      for warfarin were: non-valvular atrial fibrillation (60%), venous thrombosis
      (17%) and rheumatic heart disease (16%). The subjects spent 50% of their total
      time within target international normalized ratio range. The average annual rates
      for major and minor bleeding events were 1.8% (95% confidence interval 0.6 to
      4.1%) and 18.5% (95% confidence interval 13.9 to 24.2%), respectively. The
      cumulative incidences of first major and minor bleeding events at 1, 2 and 3
      years were 3%, 4%, 5% and 15%, 24% and 37%, respectively. Intensity of
      anticoagulation was the only predictive factor identified to be associated with
      bleeding complications. CONCLUSIONS: Among Chinese patients receiving long-term
      warfarin, major hemorrhage occurred at an acceptable range in clinical practice,
      while considerable minor bleeding was observed. Utilization of oral
      anticoagulants in Chinese patients appears safe and should be advocated in
      situations with appropriate indications.

PMID- 15146900
TI  - Association of asthma with gastroesophageal reflux disease in children.
AB  - BACKGROUND: The objective in this study was to assess the association of
      gastroesophageal reflux disease (GERD) with asthma in pediatric patients.
      METHODS: Thirty-six pediatric patients who were diagnosed as having bronchial
      asthma were included in the study. The male-to-female ratio was 2 to 1. The
      diagnosis of GER was made by 24-hour pH monitoring. RESULTS: GER was present in
      27 of 36 (75%) patients, of whom 19 (70%) were male and 8 (30%) were female
      patients. The GER frequency was found to be different between the supine and
      upright positions (p < 0.05). GER was more frequent in the upright position.
      However, duration of GER was longer in the supine position than the upright
      position (p < 0.05). Overall reflux duration was similar in both positions (p >
      0.05). CONCLUSIONS: Demonstration of the relationship between asthma and GER
      suggests that GER is involved substantially in the pathogenesis and/or
      symptomatology of asthma. The patients with asthma should be evaluated for the
      presence of GER even in the absence of GER-related symptoms.

PMID- 15146902
TI  - Assessment of CT urography in the diagnosis of urinary tract abnormalities.
AB  - BACKGROUND: To evaluate the accuracy of helical computerized tomography urography
      (CTU) in diagnosing urinary tract disease. METHODS: We collected 102 patients who
      underwent CTU from March 2001 to September 2002. The clinical symptoms of these
      patients included: flank pain or hematuria, which were clinically suggestive of
      urinary system disorders. All patients received CT scan with or without
      intravenous contrast medium administration, except patients who had allergy
      history or poor renal function. Reformatted CT urography was performed and the
      accuracy of imaging diagnosis was evaluated. RESULTS: Of these 102 patients, 40
      cases were proved to have urolithiasis, 24 cases were with renal or ureteral
      tumors, and there were 38 cases of other urinary system disorders (including
      inflammation, ureteral stricture and congenital anomalies). Precontrast CTU
      correctly diagnosed 39 of 40 urolithiasis cases (97.5%). Precontrast and contrast
      enhanced CTU were performed in the non-urolithiasis group and correctly diagnosed
      23 cases of renal or ureteral tumors, 4 cases of congenital disorder (2
      duplications, 1 congenital renal agenesis due to VATER syndrome and 1 retrocaval
      ureter). Five of 34 patients with chronic inflammatory process of urinary tract
      or ureteral stricture were indistinct from malignancies according to the imaging
      of CT urography. CONCLUSIONS: CTU is good modality for demonstration of urinary
      tract disorders. It is better in showing radiolucent stones and non-opacified
      urinary system. CTU demonstrates more soft tissue information than IVU in the
      patients with urinary tract tumors. CTU may be an alternative modality for
      patients with deterioration of renal function or allergic history of contrast
      medium.

PMID- 15146901
TI  - A longitudinal study of growth patterns in school children in Taipei area I:
      growth curve and height velocity curve.
AB  - BACKGROUND: It has been pointed out that longitudinal rather than cross-sectional
      growth standards should be used to assess individual linear growth. The purpose
      of this study is to investigate the growth characteristics of school boys and
      girls living in Shih-Pai district in Taipei. METHODS: A defined group of 1,139
      healthy school children (570 boys and 569 girls) from the Shih-Pai district of
      Taipei city were followed longitudinally for 3 to 4 years. Anthropometric
      measurement of height and weight and physical development in each child were
      obtained. The annual increments were calculated every 6 months to map the peak
      height velocity (PHV), height velocity curve (HVC), peak weight velocity (PWV)
      and weight velocity curve (WVC). RESULTS: The age at peak velocity was taken as
      12.5 years for boys and 10.5 years for girls, and the whole year PHV as 8.0 cm/yr
      in boys and 7.0 cm/yr in girls. The mean PHV was less than 1 cm in boys and girls
      of about 17 years and 15 years, respectively, with mean heights of 170.8 cm and
      158.7 cm, respectively. CONCLUSIONS: Our preliminary results were actually
      calculated from the combination of longitudinal data and cross-sectional data
      pools. Since this is only a pilot study design, we expect that a longer follow-up
      period of the same cohorts would give more exact growth characteristics.

PMID- 15146903
TI  - Results of surgical treatment for peripheral arterial occlusive disease in women.
AB  - BACKGROUND: The incidence and prevalence of peripheral arterial occlusive disease
      (PAOD) in women is more prevalent than generally appreciated, and the results of
      surgical treatment are not certain. The purpose of this study was to investigate
      the result of surgical treatment of PAOD in female patients in our service.
      METHODS: Medical records of female patients undergoing surgical treatment for
      PAOD in Taipei Veteran General Hospital from January 1, 1997 to July 31, 1998
      were reviewed retrospectively. The clinical variables were evaluated, including
      age, smoking, diabetes mellitus, hypertension, renal function, coexistent
      coronary disease, history of stroke, Fontaine stages, surgical procedures and
      results. RESULTS: There were 20 female patients undergoing surgical treatment for
      PAOD during the study period, aged from 57 to 91 years, with an average of 73.7
      +/- 2.2. Four patients presented with rest pain. Twelve patients presented with
      gangrene of lower limbs. Ten patients underwent bypass surgery. Three patients
      received embolectomy. One patient underwent below knee amputation after femoro
      popliteal bypass. One patient underwent below knee amputation after embolectomy.
      Five patients underwent above knee amputation without bypass surgery or
      embolectomy. Four patients (20%) died after surgery. CONCLUSIONS: The female
      patients of PAOD presented with severe symptoms and advanced Fontaine stages. The
      delay in diagnosis and referral resulted in an unsatisfying outcome of surgical
      treatment. An aggressive approach in diagnosis and referral is necessary for
      better results.

PMID- 15146904
TI  - Hepatoblastoma and hepatocellular carcinoma in children.
AB  - BACKGROUND: After nation-wide hepatitis B vaccination in Taiwan, the authors
      reviewed retrospectively their experience to investigate how the histopathology
      type of pediatric malignant hepatic tumors changed and whether the survival rate
      was improved with current surgical technique and adjuvant chemotherapy. METHODS:
      Cases of hepatoblastoma and hepatocellular carcinoma were retrospectively
      analyzed and divided into 2 groups by time of diagnosis. Group I was those who
      received treatments during 1978 to 1990. Group II was those treated during 1991
      to 2001. RESULTS: There were 20 cases of hepatoblastoma and 15 cases of
      hepatocellular carcinoma. Male predominance was noted in both groups
      (male:female, 12:8 and 9:6, respectively). The patients with hepatoblastoma were
      younger than those with hepatocellular carcinoma (mean/range, 9/2-36 months and
      10/0.7-15 years, respectively). Cases of hepatocellular carcinoma were all
      hepatitis B carriers. The ratio of hepatoblastoma:hepatocellular carcinoma
      increased from 11:12 in group I to 9:3 in group II. Three-year survival rate of
      hepatoblastoma was zero in group I and 55% (5/9) in group II. Three-year survival
      rate of hepatocellular carcinoma was zero in both groups. Operative mortality was
      9% (2/23) in group I and zero in group II. CONCLUSIONS: Since the institution of
      national program of universal hepatitis B vaccination, the incidence of
      hepatocellular carcinoma in children have declined in Taiwan. The improved
      survival of hepatoblastoma resulted from better surgical technique and
      chemotherapy.

PMID- 15146905
TI  - Disseminated cryptococcosis with pulmonary and marrow involvement mimicking
      radiological features of malignancy.
AB  - The most commonly involved sites of cryptococcosis are the lungs and the central
      nervous system. Cryptococcal osteomyelitis is a rare complication of disseminated
      cryptococcosis, and the vertebraes are the most common site of this infection.
      The most common underlying disease is sarcoidosis, followed by tuberculosis and
      previous steroid therapy. Conservative treatment alone or treatment with a
      combination of the medical and surgical curettage is successful in most cases. We
      report a case of cryptococcal osteomyelitis in a 63-year-old immunocompetent male
      who presented with lower back pain over the sacral region for several years.
      Radiologic studies showed a pulmonary mass and a radiolytic lesion involving the
      left ischial bone, which mimicked pulmonary malignancy with bone metastasis.
      Biopsy of the lung mass and the bone lesion revealed abundant cryptococcal
      organisms, and cryptococcal osteomyelitis was diagnosed.

PMID- 15146906
TI  - Ocular injuries from plant sap of genera Euphorbia and Dieffenbachia.
AB  - Clinical findings in 3 cases of ocular injuries caused by the milky latex from
      Euphorbia tirucalli and Dieffenbachia sequine were reported. The initial symptoms
      of all patients were burning pain with subsequently blurred vision. Visual acuity
      was reduced between 6/30 and 6/20. Euphorbia sap caused punctate erosion,
      microbullae and Descemet's folds; while Dieffenbachia sap induced conjunctival
      chemosis and fine blue crystals in the stroma. Ocular symptoms developed in 5 to
      18 hours despite immediately copious irrigation. Supportive treatment resulted in
      a full recovery without sequalae over 1 week. Wearing eye protection and washing
      the exposed areas with soap and water are advised while handling such plants.

PMID- 15146907
TI  - Huge aneurysmal bone cyst of iliac bone in a mid-aged female.
AB  - Aneurysmal bone cyst is a rare nonneoplastic expansile osteolytic bone lesion of
      unknown etiology. It usually occurs in the first 2 decades of life. The most
      common sites are the metaphysio-epiphyseal areas of long bones or vertebrae with
      eccentric expansion. We present a 42-year-old female with a huge aneurysmal bone
      cyst of the pelvis with dumbbell-shaped expansion on the both side of the iliac
      bone, which grew rapidly in 6 months. We also review the literature and discuss
      its prevalence, clinicopathologic characteristics, differential diagnostic
      problems, optimal treatment, and the potential of recurrence.

PMID- 15146908
TI  - Malignant fibrous histiocytoma of the maxillary sinus presenting as toothache.
AB  - Malignant fibrous histiocytoma (MFH) is a high-grade and aggressive sarcoma. It
      is relatively rare in the head and neck region. Its diagnosis is based on
      immunohistochemical stains. Wide excision followed by postoperative radiotherapy
      is believed to be the treatment of choice for MFH. In October 2001, a case of MFH
      in the maxillary sinus, which presented as a toothache at the beginning, was
      successfully diagnosed and treated. Using the external approach, the tumor mass
      was completely removed, and postoperative radiotherapy was subsequently
      performed. Seventeen months after the surgery, the patient was clinically well
      without any evidence of local recurrence or distant metastasis.

PMID- 15146909
TI  - High-salt stacking principles and sweeping: comments and contrasts on mechanisms
      for high-sensitivity analysis in capillary electrophoresis.
AB  - High-salt stacking in electrokinetic chromatography (EKC) is defined and
      contrasted to the sweeping method. A recent paper argued the two methods are
      identical, where high concentrations of micelle in the sample were intended to
      mimic the effect of high-salt stacking. However, high micelle concentration in
      the sample matrix in EKC is analogous to using a high-conductivity sample instead
      of a low-conductivity sample in field amplified stacking. High-salt stacking does
      not require a sample free of pseuostationary phase, only a sample with a high
      mobility co-ion compared to the separation buffer electrokinetic vector. High
      salt stacking uses a discontinuous buffer system and should not be confused with
      continuous buffer stacking systems such as sweeping.

PMID- 15146910
TI  - Development of new solid-phase microextraction fibers by sol-gel technology for
      the determination of organophosphorus pesticide multiresidues in food.
AB  - Allyloxy bisbenzo 16-crown-5 trimethoxysilane was first used as precursor to
      prepare the sol-gel-derived bisbenzo crown ether/hydroxyl-terminated silicone oil
      (OH-TSO) SPME coating. The coating procedure involving sol solution composition
      and conditioning process was presented. Compared with commercial SPME stationary
      phases, the new coatings showed higher extraction efficiency and therefore could
      provide higher sensitivity for organphosphorous pesticides (OPs). Limits of
      detection (LODs) were in the range of 0.003-1.0 ng/g for these OPs in food
      samples (honey, juice, orange and pakchoi). The optimal extraction conditions of
      the new coatings to OPs in these samples were investigated by adjusting
      extraction time, salt addition, extraction temperature, and dilution ratios of
      samples with distilled water by using SPME coupled with gas chromatography (GC)
      flame photometric detection (FPD). The method was applied to determine the
      concentrations of OPs in real samples.

PMID- 15146911
TI  - Advanced mesoporous organosilica material containing microporous beta
      cyclodextrins for the removal of humic acid from water.
AB  - A new mesoporous organosilica material (beta-CD-Silica-4%) containing microporous
      beta-cyclodextrins (beta-CDs) has been prepared by the co-polymerization of a
      silylated beta-CD monomer with tetraethoxysilane in the presence of a structure
      directing template, cetyltrimethylammonium bromide. Solid-state 13C and 29Si NMR
      studies provided evidence for the presence of covalently attached beta-CDs in the
      mesoporous material. Nitrogen adsorption experiments showed that beta-CD-Silica
      4% material had a BET surface area of 460 m2/g and an average mesopore diameter
      of 2.52 nm. Small-angle powder X-ray diffraction pattern of beta-CD-Silica-4%
      material revealed the lack of highly ordered mesoporous structure. Adsorption
      experiments showed that beta-CD-Silica-4% material removed up to 99% of humic
      acid from an aqueous solution containing 50 ppm of humic acid at a solution-to
      solid ratio of 100 ml/g.

PMID- 15146912
TI  - On-line coupling of flow injection displacement sorption preconcentration to high
      performance liquid chromatography for speciation analysis of mercury in seafood.
AB  - A simple and cost-effective method for speciation analysis of trace mercury in
      seafood was developed by on-line coupling flow injection microcolumn displacement
      sorption preconcentration to high-performance liquid chromatography (HPLC) with
      UV detection. The methodology involved the presorption of the Cu-PDC (pyrrolidine
      dithiocarbamate) chelate onto a microcolumn packed with a cigarette filter
      sorbent, simultaneous preconcentration of Hg(II), methylmercury (MeHg),
      ethylmercury (EtHg), and phenylmercury (PhHg) onto the microcolumn through a
      displacement reaction with the presorbed Cu-PDC, and their subsequent elution
      from the microcolumn for on-line HPLC separation. Interferences from heavy metal
      ions with lower stability of their PDC chelates relative to Cu-PDC were minimized
      without the need of any masking agents. With the consumption of 4.0 ml of sample
      solution, the enrichment factors were about 80. The detection limits were 10-25
      ng g(-1) (as Hg) in fresh tissue. Precision (R.S.D. (%), n = 5) ranged from 2 to
      3% at the 500 microg l(-1) (as Hg) level. The developed technique was validated
      by analyzing a certified reference material (DORM-2, dogfish-muscle), and was
      shown to be useful for mercury speciation in real seafood samples.

PMID- 15146913
TI  - Practical aspects of fast reversed-phase high-performance liquid chromatography
      using 3 microm particle packed columns and monolithic columns in pharmaceutical
      development and production working under current good manufacturing practice.
AB  - The potential and limitations of fast reversed-phase high-performance liquid
      chromatographic separations for assay and purity of drug substances and drug
      products were investigated in the pharmaceutical industry working under current
      good manufacturing practice using particle packed columns and monolithic columns.
      On particle packed columns, the pressure limitation of commercially available
      HPLC systems was found to be the limiting factor for fast separations. On 3
      microm particle packed columns, HPLC run times (run to run) for assay and purity
      of pharmaceutical products of 20 min could be achieved. As an interesting
      alternative, monolithic columns were investigated. Monolithic columns can be
      operated at much higher flow rates, thus allowing for much shorter run times
      compared to particle packed columns. Compared to particle packed columns, the
      analysis time could be reduced by a factor up to 6. However, some compounds
      investigated showed a dramatic loss of efficiency at higher flow rates. This
      phenomenon was observed for some larger molecules supporting the theory that mass
      transfer is critical for applications on monolithic columns. At flow rates above
      3 ml/min some HPLC instruments showed a dramatic increase in noise, making
      quantifications at low levels impossible. For very fast separations on monolithic
      columns, the maximum data acquisition rate of the detector is the limiting
      factor.

PMID- 15146914
TI  - Monolithic silica columns with chemically bonded tert-butylcarbamoylquinine
      chiral anion-exchanger selector as a stationary phase for enantiomer separations.
AB  - An enantioselective silica rod type chiral stationary phase (CSP) is presented as
      a novel combination of the well-known enantiomer separation properties of
      immobilized tert-butyl-carbamoylquinine chiral anion-exchanger selector with the
      unique properties of monolithic silica material. The chromatographic behavior of
      the tert-butyl-carbamoylquinine silica rod was studied and compared with a
      similar prepared particulate material. Good selectivities were achieved for a
      spectrum of chiral test components like N-derivatized amino acids (DNB- Ac-, DNZ
      , Bz-, Z-amino acids) and for Suprofen. The influence of mobile phase parameters,
      as well as the effect of serially coupling up to six 10 cm monolithic silica
      columns was studied and put in context to conventional columns of particulate 5
      microm type CSP. Using that 60 cm long monolithic column it was possible to
      improve the enantiomer separation of Suprofen and achieve a baseline separation
      in less than 10 min of total separation time.

PMID- 15146915
TI  - Separation of phosphatidylcholine and phosphatidylethanolamine by using high
      performance displacement chromatography.
AB  - A binary mixture of phosphatidylcholine (PC) and phosphatidylethanolamine (PE)
      was successfully separated by high-performance displacement chromatography (HPDC)
      on an 150 mm x 4.6 mm analytical silica column (3-5 microm packing), using
      dichloromethane-methanol (9:1, v/v) as carrier and ethanolamine as displacer. The
      effects of displacer concentration, flow-rate, loading amount and the composition
      of the sample on separation efficiency were studied. Eighty-four milligrams
      sample (PE:PC 1:1.16) was separated perfectly by using 83 mM ethanolamine (in
      carrier) as displacer at the flow-rate of 0.1 ml/min. The yields of the pure PE
      and PC (100% purity) were 94.8% and 87.9%, respectively and the cycle time for a
      single separation was about 195 min. It was valuable that the optimum loading
      amount (the allowed maximum of sample loading) was investigated only by using the
      sample to be simulated the composition of the separated actual one, because the
      separation efficiency was significantly affected by the composition of the
      sample. For the same loading amount of 175 mg, the yields of the pure PE and PC
      were improved greatly from 31.4 and 16.9 to 56.0 and 77.6%, respectively, when
      the proportion of PE to PC was adjusted from 1:1.16 to 1:4. Furthermore, the
      separation of PE and PC in an actual sample (soybean phospholipids) was achieved
      using the proposed HPDC method.

PMID- 15146916
TI  - Streptavidin chiral stationary phase for the separation of adenosine enantiomers.
AB  - In this paper, a microbore column packed with streptavidin particles was used, at
      various temperatures (0-24 degrees C), to separate the adenosine enantiomers by
      HPLC. Using an aqueous mobile phase, the apparent enantioseparation was high for
      a small molecule, varying from 11.5 at 0 degrees C to 6.2 at 24 degrees C. From
      the experiments carried out with a streptavidin-biotin complex stationary phase,
      it was demonstrated that the blockage of the biotin sites of the immobilized
      streptavidin was responsible for a strong decrease in the enantioselectivity via
      a direct and/or an indirect effect. From the analysis of the concentration
      dependencies of the solute retention factor, it was also shown that a reduction
      of the D-adenosine specific binding sites occurred at the lowest temperature. The
      thermodynamic parameters determined from the van't Hoff plots indicated that the
      D-adenosine binding to the streptavidin specific sites was enthalpically driven.

PMID- 15146917
TI  - Application of liquid chromatography with electrospray tandem mass spectrometry
      to the determination of a new generation of pesticides in processed fruits and
      vegetables.
AB  - This paper describes a method for the sensitive and selective determination of 24
      new pesticide residues (azoxystrobin, trifloxystrobin, kresoxim-methyl,
      fenazaquin, indoxacarb, fenothiocarb, furathiocarb, benfuracarb, imidachloprid,
      dimethomorph, fenpyroximate, hexythiazox, tebufenpyrad, tebufenozide,
      difeconazole, fenbuconazole, flusilazole, paclobutrazol, tebuconazole,
      tetraconazole, bromuconazole, etofenprox, fenhexamid, pyridaben) in apple puree,
      concentrated lemon juice and tomato puree. A miniaturized extraction-partition
      procedure requiring small amounts of non-chlorinated solvents was used. The
      extracts are analyzed by liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-ESI-MS-MS) without any further clean-up step. The
      pesticides are separated on a reversed-phase polar column using a gradient
      elution. Fifty-five simultaneous MS-MS transitions of precursor ions were
      monitored (two or three for each pesticide). Studies at fortification levels of
      0.001-0.020 and 0.010-0.200 mg/kg gave mean recoveries ranging from 76 to 106%
      for all compounds, except for imidacloprid, with (R.S.D.s) < or = 15%. The
      excellent sensitivity and selectivity of LC-MS-MS method allowed quantitation and
      identification at low levels also in difficult matrices with a run time of 20
      min. With the developed method almost 100 samples of commercial fruit products
      (nectars, juices, purees) were analyzed. None of samples contained residues
      higher than 0.010 mg/kg.

PMID- 15146918
TI  - Isolation and purification of honokiol and magnolol from cortex Magnoliae
      officinalis by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography was used to isolate and purify honokiol
      and magnolol from cortex Magnoliae Officinalis (Magnolia officinalis Rehd. et
      Wils.), a plant used in the traditional Chinese medicine. A crude sample, 150 mg,
      was successfully separated with a two-phase solvent system composed of n-hexane
      ethyl acetate-methanol-water (1:0.4:1:0.4, v/v), and the fractions were analyzed
      by high-performance liquid chromatography. The separation produced 80 and 45 mg
      of honokiol and magnolol with purities of 99.2 and 98.2%, respectively, in 2.5 h.

PMID- 15146919
TI  - Products of the reaction between alpha- or gamma-tocopherol and nitrogen oxides
      analyzed by high-performance liquid chromatography with UV-visible and
      atmospheric pressure chemical ionization mass spectrometric detection.
AB  - The reaction products of alpha- or gamma-tocopherol with nitric oxide in the
      presence of molecular oxygen were isolated and characterized. The consumption of
      tocopherols and the formation of the major products were monitored by high
      performance liquid chromatography (HPLC) by a gradient elution method. The
      quantitative analysis of these compounds with UV-Vis detectors, however, was
      interfered by several minor products having similar UV spectra and retention
      times as those of the major ones. In order to establish a quantitative analytical
      method for the products, we investigated other detection methods, and found that
      atmospheric pressure chemical ionization (APCI), LC-MS was a more selective and
      better analytical method for these compounds.

PMID- 15146920
TI  - Cloud point extraction for high-performance liquid chromatographic speciation of
      Cr(III) and Cr(VI) in aqueous solutions.
AB  - Cloud point extraction (CPE) was applied as a preconcentration step for HPLC
      speciation of chromium in aqueous solutions. Simultaneous preconcentration of
      Cr(III) and Cr(VI) in aqueous solutions was achieved by CPE with
      diethyldithiocarbamate (DDTC) as the chelating agent and Triton X-114 as the
      extractant. Baseline separation of the DDTC chelates of Cr(III) and Cr(VI) was
      realized on a RP-C18 column with the use of a mixture of methanol-water
      acetonitrile (65:21:14, v/v) buffered with 0.05 M NaAc-HAc solution (pH 3.6) as
      the mobile phase at a flow rate of 1.0 ml min(-1). The precision (R.S.D.) for
      eight replicate injections of a mixture of 100 microg l(-1) of Cr(III) and Cr(VI)
      were 0.6 and 0.5% for the retention time, 4.1 and 4.6% for the peak area
      measurement, respectively. The concentration factor, which is defined as the
      concentration ratio of the analyte in the final diluted surfactant-rich extract
      ready for HPLC separation and in the initial solution, was 65 for Cr(III) and 19
      for Cr(VI). The linear concentration range was from 50 to 1000 microg l(-1) for
      Cr(III) and 50-2000 microg l(-1) for Cr(VI). The detection limits of Cr(III) and
      Cr(VI) were 3.4 and 5.2 microg l(-1), respectively. The developed method was
      applied to the speciation of Cr(III) and Cr(VI) in snow water, river water,
      seawater and wastewater samples.

PMID- 15146921
TI  - Study of microporosity of active carbon spheres using inverse gas chromatographic
      and static adsorption techniques.
AB  - Active carbon spheres (ACSs) with different porous structures prepared in the
      laboratory were characterized by static adsorption studies and inverse gas
      chromatographic (IGC) technique. Surface properties such as BET surface area,
      micropore volume and pore size in different regions of porosity were determined
      using different theoretical approaches. Thermodynamic parameters such as
      isosteric heat of adsorption, free energy of adsorption and dispersive component
      of the surface energy were determined using IGC technique from corrected
      retention volume of normal alkanes and corresponding branched alkanes.
      Thermodynamic parameters were used to assess the molecular sieving property of
      ACSs. It is observed that thermodynamic properties strongly depend on microporous
      character of ACSs. The variations observed in pore size determined by both of the
      techniques that is by static adsorption measurements and IGC may be attributed to
      the variation in analysis temperature, i.e. liquid N2 temperature for adsorption
      studies and elevated temperature for IGC technique.

PMID- 15146922
TI  - Interlaboratory evaluation of injection techniques for triglyceride analysis of
      cocoa butter by capillary gas chromatography.
AB  - As part of two international collaborative studies, in which 14 laboratories
      applied capillary GLC to determine the triglyceride (TG) profile of cocoa butter,
      the performance of different sample introduction techniques, i.e. cold on-column
      injection (OCI), split injection and programmed-temperature vapouriser (PTV)
      injection, was compared. In both studies, the participants did not apply a
      uniform GLC procedure. Synthetic mixtures of triglycerides were chosen to permit
      an accurate determination of detector response factors. No statistically
      significant difference was found between the mean values obtained by different
      injection modes. The OCI, generally recommended as best practice, did not give
      superior results than the PTV or the split injection techniques.

PMID- 15146923
TI  - Resolution of overlapped non-absorbing and absorbing solutes using either an
      absorption null-balance detection window or multivariate deconvolution applied to
      capillary electrophoresis of anionic surfactants.
AB  - Non-absorbing alkyl ether sulfates (AES) can be separated using anthraquinone-2
      carboxylic acid (AQCA) as a probe; however, absorbing alkyl benzene sulfonates
      (ABS), if present, interfere indirect detection of most AES oligomers. Overcoming
      of this interference, as well as the simultaneous characterisation and evaluation
      of AES, fatty acids and ABS, was accomplished by using a diode-array detector and
      the procedures here discussed. First, it was shown that ABS can be made
      undetectable by using a 9 nm wide and 227 nm centred charge-absorptivity null
      balance detection window (NBDW), where its contribution to the absorbance cancels
      the dilution effects that its presence induces on the signal of the background
      chromophore (BGC). Two other procedures, not requiring any prior knowledge on the
      nature of the absorbing interference, were also addressed. In the first one, the
      NBDW procedure was emulated by software, by treating the time-wavelength data
      matrix stored during the experimental run, and in the second one, both the ABS
      and BGC spectra, and the concentration profiles of ABS and the non-absorbing
      solutes, were recovered by orthogonal projection approach (OPA) and alternating
      least squares (ALS). The OPA-ALS processing provided the deconvolved signals and
      the wavelengths required to implement the experimental and software-emulated NBDW
      procedures. A composite ABS spectrum and a mixed concentration profile of the non
      absorbing solutes, that involves mutual ABS-BGC dilution effects are enclosed in
      the OPA-ALS straightforward solutions. The pure spectra and concentration
      profiles were finally retrieved by crossed orthogonalisation. For the NBDW
      procedures, the limits of detection (S/N = 3) for AES oligomers overlapped by
      1500 microg ml(-1) ABS were of ca. 10 microM AES. Using decyl sulfate as internal
      standard, the relative standard deviation for AES in an ABS containing industrial
      sample was 4.5%. The procedures here described are useful to remove the
      interference produced by any absorbing solute when overlapped with indirectly
      detected solutes in both capillary electrophoresis (CE) and HPLC.

PMID- 15146924
TI  - Quantitative analysis of imazamox herbicide in environmental water samples by
      capillary electrophoresis electrospray ionization mass spectrometry.
AB  - Capillary electrophoresis-mass spectrometry (CE-MS) with an electrospray
      ionization interface was applied for the quantitative analysis of imazamox
      pesticide in well water, potable water, and pond water. The detector response for
      imazamox was determined to be linear over the concentration range of 50-1 ng/ml.
      The limits of quantitation and detection of the method were determined to be 200
      and 20 ng/l for imazamox compound in each type of water sample, respectively. The
      total sample preparation and CE-MS analysis time was under 2 h.

PMID- 15146925
TI  - Ion chromatographic determination of trace level phosphorus in purified quartz.
AB  - Trace levels of phosphorus in purified quartz are determined by ion
      chromatography. In situ reagent purification, matrix digestion and oxidation of
      phosphorus to orthophosphate ion are carried out simultaneously in a vapour phase
      digestion (VPD) assembly using a mixture of HF, HNO3 and H2O2. A drastic
      reduction (475 times) in phosphate blank from reagents (HF/H2O2) was achieved in
      the VPD through in situ purification of the reagent. The residues remaining after
      volatilisation (solvent/matrix), mostly consisting of insoluble
      phosphate/fluoride salts of divalent and trivalent cations, were solubilised by
      ion-exchange dissolution. Phosphate was analysed on the IonPac AS17 column with
      suppressed conductivity detection. The results of the ion chromatography (IC)
      method were compared with a spectrophotometric method. Accuracy was evaluated by
      analysing a certified reference material (silicon, NIST 57a). The method
      detection limit was 0.05 microg g(-1).

PMID- 15146926
TI  - Separation of rutin nona(H-) and deca(H-) sulfonate sodium by ion-pairing
      reversed-phase liquid chromatography.
AB  - Ion-pairing reversed-phase liquid chromatography (RPLC) was used to separate two
      polysulfonates, rutin nona(H-) sulfonate sodium and rutin deca(H-) sulfonate
      sodium, which have very similar chemical structures. The final product always
      contained both of them when one of the compounds was synthesized. Baseline
      separation was achieved on a C8-bonded silica column at ambient temperature. The
      eluent was acetonitrile-15 mM phosphate buffer solution containing 20 mM TBA (pH
      6.0) (46:54, v/v). The calibration plot was linear in the concentration range 0.5
      200 microg ml(-1) for both analytes. The limits of detection (LODs; 254 nm) were
      0.03 microg ml(1-) for rutin nona(H-) sulfonate sodium and 0.04 microg ml(-1) for
      rutin deca(H-) sulfonate sodium. Three batches of rutin deca(H-) sulfonate sodium
      were analyzed using the assay; the results showed that the analytical performance
      is really satisfactory.

PMID- 15146928
TI  - Simultaneous determination of ergosterol, nucleosides and their bases from
      natural and cultured Cordyceps by pressurised liquid extraction and high
      performance liquid chromatography.
AB  - A simple method is described for the simultaneous determination of ergosterol,
      nucleosides and their bases in Cordyceps. The samples were extracted by using
      pressurised liquid extraction (PLE). The effects of experimental variables, such
      as solvent, temperature, static extraction time and cycles, on PLE efficiency
      have been studied. The results showed a strong influence of the solvent and
      temperature on extraction efficiency of PLE. The determination was achieved by
      high-performance liquid chromatography (HPLC) using a Zorbax NH2 analytical
      column (250 x 4.6 mm i.d., 5 microm) with diode-array detector (DAD). The
      automated preparation of the sample permits a very fast analysis which is an
      important goal for routine purpose.

PMID- 15146929
TI  - Essential oil composition of the leaves and stems of Meum athamanticum Jacq.,
      from Spain.
AB  - The essential oil of the leaves and stems of Meum athamanticum Jacq., has been
      extracted by steam distillation and analysed by gas chromatography (GC) and gas
      chromatography coupled to mass spectrometry (GC-MS). The monoterpene fraction was
      predominant while the sesquiterpene one was practically absent. The principal
      constituents have been identified as (E)-beta-ocimene (29.6%), gamma-terpinene
      (17.9%), terpinolene (17.0%) and p-cymene (9.7%). Our results show that the
      chemical composition of the essential oil obtained of the leaves and stems of M.
      athamanticum from Spain is different to that obtained from plants of Germany,
      Italy and France.

PMID- 15146927
TI  - Liquid chromatography/quadrupole time-of-flight mass spectrometry for
      determination of saxitoxin and decarbamoylsaxitoxin in shellfish.
AB  - Saxitoxin (STX) and decarbamoylsaxitoxin (dcSTX) were determined by liquid
      chromatography with quadrupole time-of-flight mass spectrometry (Q-TOF MS). A
      shellfish tissue was extracted with 0.1 mol/l HCl under ultrasonication, and
      cleanup of extract was accomplished by solid-phase extraction with a C18
      cartridge. Chromatographic separation was carried out on a C18 column (150 mm x
      2.1 mm, 3.5 microm) with gradient elution of MeOH-H2O (20:80) containing 0.05%
      heptafluorobutyric acid and MeOH-H2O (15:85) containing 0.05% acetic acid. The
      protonated molecule [M + H]+ ions at m/z 257 for dcSTX and 300 for STX were
      selected in precursor ion scanning for Q-TOF MS in the positive electrospray
      ionizaion mode. Average recoveries and relative standard deviations, by analyzing
      samples spiked at a level of 0.1, 0.8 or 1.6 microg/g, were 84-92 and 8-14%,
      respectively. Identification of the presence of the toxins in shellfish tissues
      was based on the structural information offered by Q-TOF MS.

PMID- 15146930
TI  - Gas chromatography using a resistively heated column with mass spectrometric
      detection for rapid analysis of pyridine released from Bacillus spores.
AB  - Gas chromatography using a resistively heated analytical column with full scan
      electron impact mass spectrometry (EI-MS) was used to detect pyridine generated
      from heating Bacillus spores in a custom designed furnace inlet, along with
      gasoline range aromatic (GRA) hydrocarbons representing an environmental
      contaminant that could interfere with detection of the biologically-derived
      compound. Gas phase materials from the furnace inlet were collected onto a
      section of cooled open tubular column, and carrier gas flow was then routed
      through the trapping column onto the analytical column. Both sections of column
      were contained within low thermal mass tubular metal sheaths, with each
      independently and resistively heated allowing rapid temperature ramps and
      cooling. An analysis time of 2 min resolved spore-derived pyridine from the other
      organics, and allowed identification by mass spectrum match. Throughput of 20
      analyses per hour was shown to be possible with a 1-min column cool-down time
      between analyses.

PMID- 15146931
TI  - Comparison of the relaxant effects of a new oxime-nitrate derived from isosorbide
      5-mononitrate and the parent drug.
AB  - The transformation of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) to the
      corresponding keto derivative and its ketoxime (oxime-nitrate derivative of
      isosorbide) is described. The effects of IS-5-MN and the new oxime-nitrate (ON)
      on the endothelial and smooth muscle cells of isolated rings of the rat superior
      mesenteric artery were examined. After contraction induced by phenylephrine, IS-5
      MN (10(-8)-10(-4) mol/l) caused a concentration-dependent relaxation. Removal of
      the vascular endothelium strongly potentiated this effect. On the other hand, the
      new ON (10(-8)-10(-4) mol/l) was a more potent relaxant than the parent drug, but
      its effect was not dependent on the vascular endothelium. The inhibitory effect
      of the artery without endothelium to the new ON was more pronounced than that to
      IS-5-MN. The mechanism of the relaxant effect of the new compound consisted in
      the liberation of nitric-oxide (NO) which activated guanylate cyclase (GC), upon
      which accumulation of cyclic guanosine monophosphate (cGMP) occurred, which was
      the second messenger leading to relaxation. Tolerance to the frequent
      applications of the new compound was not observed, moreover a slight increase of
      the effect was detected in comparison with IS-5-MN for which tolerance was
      observed to a great extent. Clinically, the new ON could be favorable in all
      types of angina in comparison with the classical IS-5-MN.

PMID- 15146932
TI  - Pharmacokinetics of three organic nitrates in Chinese healthy male volunteers.
AB  - Eighteen Chinese male subjects completed a single-blind, randomized, three
      treatment, three-period, cross-over study. In each treatment phase, subjects
      received a single dose of 20 mg isosorbide dinitrate (CAS 87-33-2, ISDN)
      intravenous infusion, 20 mg isosorbide 5-mononitrate (CAS 16051-77-7, 5-ISMN)
      tablet or 20 mg isosorbide 5-mononitrate intravenous infusion. Each consecutive
      dosing was separated by a washout period of 7 days. Following each dosing, venous
      blood samples were collected over a period of 16 h. Plasma concentrations of ISDN
      and its two active metabolites isosorbide 2-mononitrate (2-ISMN), 5-ISMN had been
      measured by a validated gas chromatographic method. Various pharmacokinetic
      parameters including AUC0-t, AUC0-infinity, Cmax, tmax, t1/2, Kelm and MRT were
      determined for the three formulations and found to be in good agreement with
      literature values. AUC0-t and AUC0-infinity of 5-ISMN tablet and intravenous
      infusion were 2694 +/- 496 ng x ml(-1) x h vs. 2548 +/- 556 ng x ml(-1) x h and
      3266 +/- 624 ng x ml(-1) x h vs. 3178 +/- 769 ng x ml(-1) x h, respectively, and
      the relative bioavailability of 5-ISMN tablet was 105 +/- 20%. As compared with 5
      ISMN intravenous infusion, ISDN can rapidly reach the plateau concentration and
      metabolize to its active metabolites 5-ISMN and 2-ISMN, which both have
      vasodilator effect. The results of this study suggest that as evaluated from the
      pharmacokinetic profiles of the three formulations, 5-ISMN tablet and ISDN
      intravenous infusion are ideal vasodilators and anti-angina drugs especially in
      acute conditions due to their rapid onset and long duration of action.

PMID- 15146933
TI  - Antitussive effects of the H1-receptor antagonist epinastine in patients with
      atopic cough (eosinophilic bronchitis).
AB  - Chronic cough is the only symptom of eosinophilic bronchitis (EB). There is
      considerable overlap between EB and atopic cough. To investigate the antitussive
      effects of a histamine H1-recetor antagonist, epinastine hydrochloride
      (epinastine, CAS 80012-43-7, Alesion; 20 mg/day, once daily), cough scores,
      pulmonary function, capsaicin cough threshold, and bronchial hyperresonsiveness
      (BHR) to methacholine (MCh) were evaluated before and after a 4-week treatment
      with epinastine in patients with EB. In the epinastine group, the cough scores
      were decreased significantly (18.3 +/- 6.1 in week 1, 17.4 +/- 6.7 in week 2,
      15.1 +/- 6.2 in week 3, 14.0 +/- 4.8 in week 4) in comparison with the value of
      35.3 +/- 8.7 in week -2). The cough threshold for capsaicin improved from 1.70 +/
      3.04 micromol/l to 12.7 +/- 17.6 micromol/l in the epinastine group (p < 0.05;
      baseline vs. week 4) The bronchial hyperresponsiveness to MCh (Dmin) did not
      change significantly either in the epinastine or the placebo groups. The morning
      and evening peak expiratory flow rate (PEFR, L/min) did not change from the
      baseline period in either the epinastine or the placebo groups. These results
      suggested that epinastine may be useful for treating patients with EB and that
      histamine H1-receptor is related to the pathophysiology of coughing in EB.

PMID- 15146934
TI  - [Effect of a Harpagophytum procumbens DC extract on matrix metalloproteinases in
      human chondrocytes in vitro].
AB  - Inflammatory articular cartilage diseases such as arthritis and osteoarthritis
      are characterized by a loss of articular cartilage due to an imbalance between
      synthesis and degradation of the extracellular cartilage matrix. These diseases
      are accompanied by an increased induction of cytokines such as interleukin 1beta
      (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). The increased release of
      cytokines leads to an enhanced production of matrix-degrading enzymes e.g. the
      matrix metalloproteinases (MMPs). In this study the direct antirheumatic effects
      of an extract of the secondary root of the African devil's claw (Harpagophytum
      procumbens DC) on the production of MMPs in IL-1beta-stimulated human
      chondrocytes were examined. A detailed evaluation by immunomorphological methods
      and Western blot analysis showed that the extracts of Harpagophytum decreased
      significantly the production of MMPs (MMP-1, MMP-3, MMP-9) in chondrocytes. The
      IL-1beta-induced production of MMPs was also significantly reduced by both a JM
      extract (Jucurba) containing 210 mg dry extract and JF-extract (Jucurba forte)
      containing 480 mg dry extract. After all it could be shown that the effect of JF
      extract on the MMP-synthesis was more pronounced in untreated and cytokine
      stimulated chondrocytes when compared with the effect of the JM-extract. The
      capability of the JM-extract to suppress the MMP-production via the inhibition of
      the synthesis of inflammatory cytokines could explain its therapeutic effect in
      arthritic inflammations. In these in vitro experiments the JF-extract showed a
      higher efficacy than the JM-extract.

PMID- 15146935
TI  - Gastric antisecretory and anti-ulcer effect of ME3407, a new benzimidazole
      derivative, in rats.
AB  - The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4
      b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and
      gastric and duodenal ulcers in rats were examined. ME3407, given orally,
      inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such
      as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and
      histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect
      on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration
      of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced
      by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg,
      respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited
      the elevation of serum gastrin level. The development of duodenal ulcers caused
      by mepirizole and systeamine was also potently inhibited by ME3407 at an oral
      dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally,
      subcutaneously or intravenously, ME3407 did not inhibit these acutely induced
      gastric elosion and acid output. ME3407 was not detected in the serum upon oral
      administration. These results indicated that ME3407 was active only by oral
      administration, and exerts direct action on the ulcers and acid secretion from
      the gastric membrane.

PMID- 15146936
TI  - Isolation and quantification of chitin-binding mistletoe lectin from mistletoe
      extracts and validation of this method.
AB  - A method was established to isolate and quantify small amounts of chitin-binding
      mistletoe lectin (cbML) from extracts of the mistletoe (Viscum album L.) by
      affinity and reverse phase high performance liquid chromatography. A validation,
      according to ICH guidelines, of this analytical method was carried out and showed
      that specificity, robustness and precision are guaranteed. In addition, linearity
      is ensured for a content between 0.6 and 4.1 microg/ml of cbML in the extracts
      and recovery was calculated to be in the range of 94 to 100%. So, accuracy of the
      method is guaranteed as well. As far as the range of the analytical method is
      concerned, a minimum of 1.2 microg and a maximum of 8.2 microg cbML can be
      incubated with the affinity material. Detection and quantitation limits were
      calculated to be 0.13 and 0.46 microg/ml cbML, respectively.

PMID- 15146937
TI  - A new gene encoding the ribosome-inactivating protein from mistletoe extracts.
AB  - Extracts from mistletoe (Viscum album L.) contain three main toxic proteins--the
      lectins MLI (also known as viscumin), MLII and MLIII. A catalytic subunit of the
      mistletoe plant toxic lectin MLIII has been cloned and expressed in Escherichia
      coli cells. The structure and immunochemical properties of recombinant MLIII A
      subunit were investigated using a panel of monoclonal antibodies against ML
      toxins. Ribosome-inactivating activity of the recombinant MLIII A-subunit was
      determined in a cell-free system exhibiting inhibition of endogenous protein
      synthesis. The comparative analysis of nucleotide and deduced amino acid
      sequences of the cloned MLIII A and the native MLI A-subunits was performed,
      revealing the main differences in the primary structure of these proteins.
      Antigenicity analysis of the MLIII A-subunit has revealed a new epitope D179-E184
      that is not present in viscumin. The role of toxic lectins with respect to the
      immunological properties of mistletoe extracts is discussed.

PMID- 15146938
TI  - Traumatic injuries of the pelvis. SIOT paper 1967.
AB  - The paper that Prof. Campanacci read at the Annual Meeting of the Italian Society
      of Orthopaedics and Traumatology in 1967 was the product of vast research aimed
      at clarifying and classifying traumatic injuries of the pelvic girdle. The basic
      idea behind the study was that correct therapeutic conduct cannot neglect an in
      depth knowledge of the pathologic anatomy and pathogenesis of the injury. What
      emerges, in addition to the knowledge of anatomopathology, is the continuing
      validity of the scientific method with which the problem was dealt with.

PMID- 15146939
TI  - Acetabular fractures.
AB  - Over the last few years an increased percentage of work-related and car accidents
      has led to a higher percentage of acetabular fractures. These injuries are among
      the most difficult to treat in orthopaedic surgery because of their anatomy and
      because of the consequent difficulty in surgical exposure. It was the purpose of
      this study to reveal the diagnostic and the therapeutic paths related to the
      treatment of these kinds of fractures, based on our experience. A total of 517
      acetabular fractures were treated over 16 years; at present, better results are
      obtained with surgical treatment than with non-surgical treatment.

PMID- 15146940
TI  - Cemented versus cementless stem-to-bone fixation: a long-term survival
      comparison.

PMID- 15146941
TI  - Ceramic on ceramic versus metal on polyethylene coupling: a long-term survival
      comparison.

PMID- 15146942
TI  - Anatomic cementless total hip arthroplasty with ceramic bearings and modular
      necks: 3 to 5 years follow-up.
AB  - Reported here are the results obtained for 216 prosthetic implants in which
      cementless arthroplasty and a modular neck were used. The advantages to using
      this method are related to the fact that it may be adapted to a variety of
      anatomical conditions.

PMID- 15146944
TI  - Computer-assisted tridimensional preoperative planning in hip revision surgery.
AB  - It is often difficult to obtain excellent clinical results in complex cases of
      hip replacement surgery. Over recent years, in order to improve the success rate
      of this type of surgery, prosthetic implants that are more ductile and more
      reliable have been developed. At the same time, important progress has been made
      in improving the accuracy of surgical method. A great deal of effort has been
      made to improve methods of preoperative planning. The world over, computerized
      systems that aid the surgeon in his or her clinical practice (CAOS systems) have
      been developed. The authors present Hip-op, a new CAOS type system, for
      preoperative planning. In particular, the use of Hip-op in some very complex
      cases of hip revision surgery is reported. Based on clinical experience, it is
      believed that Hip-op is a useful system, one that is easy to use, and that it is
      capable of improving the accuracy of surgery.

PMID- 15146943
TI  - Hip arthroplasty after femoral osteotomy.
AB  - Osteotomy of the proximal femur is performed to treat numerous hip pathologies in
      order to improve the load axis of the coxofemoral joint, thus improving coverage
      of the femoral head; despite this, arthrosis-related pathology may progress, and
      this nearly always results in hip arthroplasty. Many authors report that the time
      interval between osteotomy and arthroplasty is approximately 5 to 10 years. It is
      the purpose of this study to evaluate the complications and the clinical and
      radiographic results of hip arthroplasty performed after proximal femoral
      osteotomy, comparing them with a control group for hip arthroplasty without
      previous osteotomy.

PMID- 15146945
TI  - Stem revision: special implant versus primary device.
AB  - The purpose of hip revision surgery is to relieve pain and restore hip function,
      while improving hip biomechanics and bone stock. The entity of bone stock
      impairment due to lysis indicates to the surgeon which revision stem he would
      preferably choose. Modern literature has described several options for stem
      revision, ranging from primary cemented/less implants in the case of limited
      proximal bone defects, to special revision stems where a massive femoral bone
      stock impairment is present. There are many classifications of the femoral bone
      stock loss in the literature but most authors seem to agree that the treatment of
      minimal proximal defects should be performed with primary implant stems. The need
      to bridge a bigger bony gap makes distal fixation a good deal. Two options are
      described for this purpose: the Wagner stem and modular stems. Wagner's concept
      consists of a distal fixation based on the interference of the straight tapered
      titanium alloy stem at the level of the femoral isthmus, while longitudinal fins
      provide rotational stability. A wide variety of modular stems was lately
      developed to prevent major complication associated to the Wagner's stem, but some
      new problems arose from proximal overfill of the canal, difficult in assembly and
      fretting corrosion. Early experience with the new ZMR taper (Zimmer, Warsaw, IN,
      USA) modular revision stem is reported.

PMID- 15146946
TI  - Hip prosthesis revisions with LS stem: indications and results.
AB  - The authors present a study that includes 350 patients affected with loosening of
      hip arthroplasty and submitted to revision with a Wagner LS stem at the 4th
      Division of the Rizzoli Orthopaedic Institute. Several different types of cotyle
      (Fitek, Wagner, Standard Cup, cemented cotyle with support ring, Octopus system)
      were used depending on the anatomopathologic findings, combined with autoplastic
      grafts. Staging and grading of loosening were based on the four G.I.R. grades. A
      clinical evaluation of results was based on the Merle D'Aubigne parameters
      modified by Charnley. For radiographic evaluation the De Lee Charnley areas were
      studied for cotyle, the Gruen areas for the femoral stem. Overall, good results
      were obtained in 175 patients, fair in 137, poor in 38.

PMID- 15146947
TI  - The biological reaction to polyethylene wear debris can be related with oxidation
      of the UHMWPE cups.
AB  - BACKGROUND: Oxidised UHMWPE due to gamma irradiation in air has a greater
      susceptibility to wear than non-oxidised UHMWPE (ethylene oxide, EtO). AIM: To
      evaluate, the biological reaction of loose implants with oxidised and non
      oxidised PE components. MATERIALS AND METHODS: Ten loose PE cups sterilised by
      EtO (group 1) and 13 sterilised by gamma irradiation in air (group 2) were
      studied. PE wear and oxidation were related to biological reaction. RESULTS:
      Group 1: PE cups had low wear score and no oxidation. In the oldest implants, a
      few PE particles and macrophages were observed in the interface membrane. Group
      2: PE inserts had medium-to-high PE wear score and variable oxidation. In the
      interface membrane, the number and total area of PE particles were high and
      variable; giant cells were more numerous than macrophages. CONCLUSION: Junctional
      tissues around loose oxidised PE components contain more PE debris and giant
      cells than membranes around PE components that are not oxidised.

PMID- 15146948
TI  - Mesenchymal stem cells and tissue engineering for orthopaedic surgery.
AB  - Bone marrow contains multipotent mesenchymal stem cells (MSCs) that can
      differentiate into different mesenchymal lineages whose end-stage cells fabricate
      bone, cartilage, tendon, fat, and other connective tissues. Our laboratory has
      been focusing on the purification, culture expansion, the in vivo and the in
      vitro characterization of MSCs and their descendants. Given the large number of
      MSCs that can be generated, we have explored their use in different pre-clinical
      models utilizing the therapeutic potentials of MSCs for musculoskeletal
      disorders. Using newly evolved tissue engineering principals, we have focus on
      the treatment of full thickness cartilage damage and, separately, bone non-union.
      The experimental results suggest the MSCs may provide a powerful therapeutic tool
      for the treatment of musculoskeletal disorders. Future efforts should be made to
      establish reliable and standardized full-scale clinical approaches using MSCs for
      orthopaedic surgery.

PMID- 15146949
TI  - [Introduction. Physiological and physiopathological roles of serotonin: recent
      data from KO mice].

PMID- 15146950
TI  - [Abnormal cardiac activity in mice in the absence of peripheral serotonin
      synthesis].
AB  - Serotonin (5-HT) controls a wide range of biological functions. In the brain, its
      implication as a neurotransmitter and in the control of behavioral traits has
      been largely documented. At the periphery, its modulatory role in physiological
      processes, such as the cardiovascular function, is still poorly understood. The
      rate limiting enzyme of 5-HT synthesis, tryptophan hydroxylase (TPH), is encoded
      by two genes: the well characterized TPH1 gene and a recently identified TPH2
      gene. Based on the study of a mutant mouse in which the TPH1 gene has been
      inactivated by replacement of the beta-galactosidase gene, we established that
      the neuronal TPH2 is expressed in neurons of the raphe nuclei and of the
      myenteric plexus, whereas the non-neuronal TPH1, as detected by beta
      galactosidase expression, is expressed in the pineal gland and the
      enterochromaffin cells. Anatomic examination of the mutant mice revealed larger
      heart sizes as compared to wild-type. Histologic investigations indicated that
      the primary structure of the heart muscle is not affected. Hemodynamic analyses
      in mutant animals demonstrated abnormal cardiac activity which ultimately leads
      to heart failure. This is the first report linking loss of TPH1 gene expression,
      and thus of peripheral 5-HT, to a cardiac dysfunction phenotype. The TPH1 -/-
      mutant may be a valuable model for investigating cardiovascular dysfunction such
      as those observed in human heart failure.

PMID- 15146951
TI  - [Genetic models to understand how serotonin acts during development].
AB  - Molecular genetics in mice have allowed significant progresses to be made in our
      understanding of the development of serotoninergic neurones and of their
      developmental role. The serotoninergic phenotype is determined by a sequence of
      transcription factors. Pet-1 is selectively expressed in the raphe and controls
      directly the transcription of the genes, encoding the biosynthetic enzyme of 5
      HT, tryptophan hydroxylase (TPH), and the serotonin plasma membrane transporter
      (SERT). Expression of SERT can however occur independently of TPH during
      development and allows subpopulations of glutamatergic neurons to take up and to
      store 5-HT into synaptic vesicles via the vesicular monoamine transporter (VMAT).
      This could allow a tight homeostasis of 5-HT receptor activation on thalamic and
      retinal afferents. Mice with an excess or a severe reduction of 5-HT during
      development, such as the MAOA and the VMAT2 KO mice, show abnormalities that
      concern late stages of development: alterations in axon branching, dendritic
      remodeling and developmental cell death. Each of these effects could be mediated
      by a different 5-HT receptor. Abnormalities have been best characterized in the
      somatosensory and visual system but are likely to occur throughout the central
      nervous system.

PMID- 15146952
TI  - [The 5-HT2B receptor: a main cardio-pulmonary target of serotonin].
AB  - In agreement with previous data in the literature, our results indicate that
      serotonin, a monoamine neurotransmitter, can also regulate cell proliferation,
      cell movements and cell differentiation. We have recently shown that serotonin is
      required for embryonic heart development. Genetic ablation of the 5-HT2B receptor
      leads to partial embryonic and postnatal lethality with abnormal heart
      development. Similar molecular mechanisms seem to be involved in adult
      cardiomyocytes since mutant mice surviving to adulthood display a dilated
      cardiomyopathy. Furthermore this receptor appears to be involved in survival of
      cardiomyocytes. The 5-HT2B receptor is also implicated in systemic hypertension.
      Furthermore, mice with pharmacological or genetic ablation of 5-HT2B receptor are
      totally resistant to hypoxia-induced pulmonary hypertension, indicating that this
      receptor is regulating the pathologic vascular proliferation leading to this
      disease. Underlying mechanisms are still to be discovered.

PMID- 15146953
TI  - [Implication of serotonin in the control of vigilance states as revealed by
      knockout-mouse studies].
AB  - Genetic manipulation of the 5-HT system leads to alterations of 5-HT
      neurotransmission and provides new opportunities to investigate the role of 5-HT
      in sleep regulations. Indeed, it represents an alternative to the use of
      pharmacological tools and, to some extent, of localized lesions of the 5-HT
      system, which have been, from the 1960s until recently, the main approaches to
      investigate this question. Homologous recombination knocking-out genes encoding
      various proteins involved in 5-HT neurotransmission in the mouse has recently
      allowed further assesment of the role of the serotonin transporter (5-HTT), the
      monoamine oxidase A (MAO-A), and the 5-HT1A, 5-HT1B and 5-HT2A receptors in the
      regulation of sleep. In 5-HT1A -/- and 5-HT1B -/- knock-out mice, Rapid Eye
      Movement sleep (REMs) was enhanced. Pharmacological blockade of these receptors
      had the same effects in wild-types. Thus, both receptor types exert a tonic
      inhibitory influence on REMs. In addition, 5-HT1A -/- and 5-HT1B -/- mutants were
      hypersensitive to 5-HT1B and 5-HT1A receptor agonists, respectively, which
      suggests that adaptive changes at 5-HT neurotransmission develop in knock-out
      animals. In the same manner, 5-HTT-/- knock-out mice exhibited increased REMs.
      This may be accounted for by a decrease in 5-HT1A and 5-HT1B receptor-mediated
      sleep regulations. In contrast, decreased REMs was observed in MAOA -/- knock
      outs, a phenomenon that mimics the effect of pharmacological MAO inhibition.
      Finally, 5-HT2A -/- and 5-HT2C -/- mice exhibited more wakefulness and less slow
      wave sleep (SWS) than wild-types. These effects could not be reproduced by 5-HT2A
      or 5-HT2c receptor blockade in wild-types. To conclude, constitutive knock-outs
      undergo adaptive processes involving other proteins than those encoded by the
      invalidated gene, which renders interpretation of the corresponding sleep
      phenotype difficult. Inducible knock-outs will probably help to overcome this
      difficulty. Finally, combination of genetic manipulations with relevant
      pharmacological ones should allow further progress in the understanding of sleep
      mechanisms.

PMID- 15146954
TI  - [Feeding disorders in 5-HT4 receptor knockout mice].
AB  - To study the functional contributions of the 5-HT4 receptor subtype of serotonin
      (5-HT), we have generated knockout mice lacking the 5-HT4 receptor gene. The male
      mutant mice exhibit a hyposensitivity to anorexic stress. Our recent data
      indicate that the pharmacological inactivation, using a systemic injection of the
      5-HT4 receptor antagonist RS39604 (0.5 mg/kg), suppressed restraint stress
      induced anorexia in wild-type female mice. In parallel, the same treatment
      reduced the 3,4-N-methylenedioxymethamphetamine (" ecstasy", 10 mg/kg)-induced
      anorexia in male wild-type mice. Our neurochemical analyses suggest that the
      mechanisms underlying feeding disorders in 5-HT4 receptor knockout mice are
      related to a lesser efficacy of 5-HT (hypothalamus, nucleus accumbens), leptin
      and the cocaine-amphetamine related transcript to reduce food intake following
      stress.

PMID- 15146955
TI  - [Introduction. Reproductive neuroendocrinology: GnRH research thirty years after
      its discovery].

PMID- 15146956
TI  - [Gonadotrophin-releasing hormone (GnRH) in the animal kingdom].
AB  - As a major actor of the brain-pituitary-gonad axis, GnRH has received
      considerable attention, mainly in vertebrates. Biochemical, molecular,
      neuroanatomical, pharmacological and physiological studies have mainly focused on
      the role of GnRH as a gonadotrophin-releasing factor and have led to a detailed
      knowledge of the hypophysiotrophic GnRH system, primarily in mammals, but also in
      fish. It is now admitted that the corresponding neurons develop from the
      olfactory epithelium and migrate into the forebrain during embryogenesis to
      establish connections with the median eminence in tetrapods or the pituitary in
      teleost fish. However, all vertebrates possess a second GnRH system, expressing a
      variant known as chicken GnRH-II in neurons of the synencephalon, whose functions
      are still under debate. In addition, many fish species express a third form,
      salmon GnRH, whose expression is restricted to neurons of the olfactory systems
      and the ventral telencephalon, with extensive projections in the brain and a
      minor contribution to the pituitary. In vertebrates, GnRHs are also expressed in
      the gonads where they act on cell proliferation and steroidogenesis in males, and
      apoptosis of granulosa cells and reinititaion of meiosis in females. These
      functions could possibly represent the primitive roles of GnRH-like peptides, as
      an increasing number of studies in invertebrate classes point to a more or less
      direct connection between GnRH-producing sensory neurons and the gonads.
      According to recent studies, GnRHs appear as very ancient peptides that emerged
      at least in the cnidarians, the first animals with a nervous system. GnRH-like
      peptides have been partially characterized in several classes of invertebrates
      notably in molluscs, echinoderms and prochordates in which effects on the
      reproductive functions, notably gamete release and steroidogeneis, have been
      evidenced. It is possible that, with the increasing complexity of metozoa, GnRH
      neurons have lost their direct connection with the gonad to specialize in the
      control of additional regulatory centers such as the hypophysis in vertebrates or
      the optic gland in cephalopods. However, reminiscent effects of GnRH functions at
      the gonadal level would have persisted due to local production of GnRHs in the
      gonad itself. Altogether, these data indicate that GnRHs were involved in the
      control of reproduction long before the appearance of pituitary gonadotrophs.

PMID- 15146957
TI  - [An antagonist to GnRH in the control of reproduction in teleost fish:
      dopaminergic inhibition. Ancestral origin and differential conservation within
      vertebrates?].
AB  - In mammals, the neurohormonal control of the pituitary gonadotropes is provided
      by the gonadoliberin GnRH. Several studies on teleost fish indicate that a single
      positive control by GnRH is not a general rule among vertebrates. Peter and
      colleagues presented the first evidence of an inhibitory neurohormonal factor,
      "GRIF" (gonadotropin-release inhibiting factor). They induced a preovulatory LH
      surge by injuring particular brain areas in the goldfish. Subsequent in vivo and
      in vitro studies identified dopamine as GRIF, and neuroanatomical investigations
      have demonstrated that dopaminergic neurones in the anterior preoptic area
      projecting to the pituitary represent the anatomical substrate for GRIF activity.
      An inhibitory role of dopamine on the control of LH and ovulation/spermiation has
      been evidenced in many adult teleosts, including its implications for
      aquaculture. However, dopamine does not play an inhibitory role in all adult
      teleosts. As regards the early stages of gametogenesis and especially the control
      of puberty, a role for dopamine has been suggested or rejected depending on
      species. The European eel has a unique life cycle with a long prepubertal stage,
      which has made it a useful model to demonstrate the key-role of dopamine in the
      control of puberty. Data from tetrapods suggest that the role of dopamine as a
      GRIF is not restricted to the teleosts, but that it may have an ancient
      evolutionary origin, and has been differentially conserved throughout vertebrate
      evolution.

PMID- 15146958
TI  - [Hypothalamic glial cells and endothelial cells as key regulators of GnRH
      secretion].
AB  - During the last decade, compelling evidence has been provided that, in addition
      of being regulated by transsynaptic inputs, GnRH neuroendocrine secretion is
      modulated by factors released both by glial cells and the endothelium of
      pituitary portal blood vessels. Glial cells exert their regulatory influence on
      GnRH release through the secretion of growth factors, such as TGFbetas and
      peptides member of the EGF family, that act either directly on GnRH neurons or
      require prostaglandin release from astrocytes, respectively. On the other hand
      vascular endothelial cells stimulate GnRH release via NO secretion. In addition,
      recent studies suggest that both glial cells and endothelial cells of the median
      eminence can modulate the direct access of GnRH neuroendocrine terminals to the
      vascular wall and thus control GnRH release efficiency. During the reproductive
      cycle, direct neurovascular contacts of GnRH nerve endings, that are engulfed in
      tanycytic endfeet, only occur at periods when massive GnRH release is required,
      i.e., at the onset of the preovulatory GnRH/LH surge on the day of proestrus.
      Recent in vitro and in vivo data demonstrate that both glial (TGFalpha and
      TGFbeta) and endothelial (NO) factors can induce such morphological plasticity.
      Neuro-glio-endothelial interactions at the median eminence of the hypothalamus
      thus appear to be key regulatory mechanisms for GnRH neuroendocrine secretion.

PMID- 15146959
TI  - [An ambiguous role of steroidogenic factor 1 in the rat GnRH receptor gene
      expression. Lessons from transgenic mice].
AB  - Because the GnRH receptor plays a paramount role within the reproductive axis,
      the understanding of the molecular apparatus that governs the tissue-specific
      expression and regulation of this gene must lead to a better knowledge of the
      physiology and the physiopathology of the gonadotrope function. To elucidate
      these mechanisms, we have used two complementary in vivo and in vitro approaches.
      Firstly, we have isolated the pituitary promoter of the rat GnRH receptor gene
      and investigated its activity using transient transfection into two gonadotrope
      derived cell lines, the alphaT3-1 and the LbetaT2 cell lines. We have thus
      defined a primary set of transcription factors involved in the tissue-specific
      expression of the GnRH receptor gene. These include the steroidogenic factor-1
      (SF-1) which plays a decisive role while functionally interacting with proteins
      related to the GATA and LIM homeodomain families of transcription factors. In
      addition, we highlighted the critical implication of SF-1 and its functional
      interaction with a CREB-related factor in the stimulatory action of PACAP
      (Pituitary Adenylate Cyclase Activating Polypeptide) on promoter activity. These
      results have led us to analyze the activity of this promoter by transgenesis in
      the mouse using human placental alkaline phosphatase as a reporter gene. In
      agreement with the in vitro data, the pituitary promoter was found to confer
      gonadotrope-specific activity in the pituitary. It was also able to direct
      transgene expression in several areas of the central nervous system known to
      express the endogenous GnRH receptor, in particular in the hippocampo-septal
      complex. Some of these tissue do not express SF-1, suggesting that, in vivo, its
      role would not be as decisive as suggested by the in vitro experiments.
      Surprisingly, during pituitary ontogenesis, the transgene is expressed as early
      as E 13.5 whereas SF-1 is not yet present in the pituitary. Thus, in vivo, SF-1
      would not be necessary for the activation of the GnRH receptor gene during the
      early developmental stages in the pituitary. These results are consistent with
      data obtained following general or pituitary-specific knockout of the gene
      encoding SF-1, suggesting that the GnRH receptor is expressed despite the absence
      of this factor. Identifying the factors responsible for the activation of the
      GnRH receptor gene at these early developmental stages should make it possible to
      refine the role of SF-1, not only in gene regulation but more generally, in the
      physiology and the physiopathology of the gonadotrope function.

PMID- 15146961
TI  - Nutritional evaluation of some Nigerian wild seeds.
AB  - Some wild seeds, namely Parkia biglobosa, Tetracarpidum conophorum, Pentaclethra
      macrophylla, Irvingia gabonensis, Afzelia africana, Prosporis africana and
      Monodora myristica, were randomly collected from various parts of Nigeria and
      analyzed with regard to their proximate, mineral, antinutrient composition and
      zinc bioavailability. The results revealed that the seeds had high protein (6.5
      24.2%), fat (19.0-58.5%), mineral (Mg, Fe, Zn, Mn, Ca, Na, K, P) and phytate
      (1043.6-2905.2 mg/100 g) contents, while the cyanide content was low (3.7-6.4
      mg/kg). However, Co, Pb and Ni were not detected in all the samples. The
      calculated [Ca] [phytate]/[Zn] molar ratios (which is the best index for
      predicting Zn bioavailability) for all the seeds revealed that Parkia biglobosa,
      Irvingia gabonensis and Prosporis africana had a calculated molar ratio above
      0.50 mol/kg (critical level), thus indicating reduced bioavailability of Zn to a
      critical level. In view of the high fat, protein, mineral and low cyanide
      contents, the high phytate content would not be expected to reduce
      bioavailability of Zn in some of the wild seeds (Afzelia africana, Pentaclethra
      macrophylla and Monodora myristica). These wild seeds could be good nutrient
      sources if integrated fully into human and animal nutrition. However, further
      studies will be carried out on the protein quality and toxicological potentials
      of these wild seeds.

PMID- 15146962
TI  - Effect of low-zinc status and essential fatty acids deficiency on the activities
      of aspartate aminotransferase and alanine aminotransferase in liver and serum of
      albino rats.
AB  - The effects of dietary deficiencies of zinc and essential fatty acids (EFAs) or
      both on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were
      investigated in young growing rats. Four groups of albino rats were fed diets
      deficient in either EFA (4% hydrogenated coconut oil) or zinc (6 ppm) or both.
      The control diet was adequate in EFA (4% soybean oil) and zinc (100 ppm). The
      feeding trial lasted eight weeks and the activities of AST and ALT were
      determined in the liver and serum. EFA deficiency had no significant (p > 0.05)
      effect on liver AST. However, zinc and the double deficiencies depressed AST
      activity in the organ. Deficiencies of EFA, zinc and their combination depressed
      ALT activity in the liver significantly (p < 0.05) with a concomitant increase
      recorded in the serum. The data suggested alteration in endothelial permeability
      of the plasma membrane and thus leakage of membrane constituents in the tissue
      studied. It is therefore considered that these deficient diets may affect liver
      tissue negatively in view of the role of these enzymes in amino acid metabolism.

PMID- 15146963
TI  - Effect of fermentation on the starch digestibility, resistant starch and some
      physicochemical properties of sorghum flour.
AB  - The effect of natural fermentation of Tabat sorghum cultivar (Sorghum bicolor L.
      Moench) at 37 degrees C for up to 36 h on pH, titratable acidity, starch
      digestibility, resistant starch and total starch was studied. The pH of the
      fermenting dough decreased sharply with a concomitant increase in the titratable
      acidity. In vitro starch digestibility markedly increased as a result of
      fermentation, while resistant starch and total starch decreased. Results showed
      that iodine absorption capacity increased during fermentation. Fermented sorghum
      had more soluble starch and swelling power at 100 degrees C than at 85 degrees C.

PMID- 15146964
TI  - Effect of gamma-irradiation on the biophysical and morphological properties of
      corn.
AB  - The effects of gamma-irradiation on the biophysical and morphological properties
      of corn plants were investigated. The irradiation doses were 0, 1, 1.5, 2.5, 5,
      and 10 krad. Corn grains exposed to 1.5 and 2.5 krad showed highly significant
      changes in all growth parameters. Fluorescence and light absorption spectra of
      chlorophyll attributed to different doses treatments of corn grains clearly
      confirmed the superiority of 1.5 krad irradiation dose in stimulating corn
      plants. Furthermore, the frequency dependence of the relative permittivity and
      the electric conductivity of the treated samples have been performed and
      discussed. The obtained results give another support via the biophysical
      properties for the 1.5 krad irradiation dose to be the most favorable one to
      improve the plant growth characteristics.

PMID- 15146960
TI  - [GnRH deficiency: new insights from genetics].
AB  - The acquisition of a sexually dimorphic phenotype is a critical event in
      mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired
      secretion of GnRH. The patients display with delayed puberty, micropenis and
      cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea
      in the female. Kallmann's syndrome (KS) is defined by the association of HH and
      anosmia or hyposmia (absent smelling sense). Segregation analysis in familial
      cases has demonstrated diverse inheritance patterns, suggesting the existence of
      several genes regulating GnRH secretion. The X-linked form of the disease was
      associated with a genetic defect in the KALI gene located on the Xp22.3 region.
      KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which
      facilitates neuronal growth and migration. Abnormalities in the migratory
      processes of the GnRH neurons with the olfactory neurons explain the association
      of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were
      found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the
      function of reproduction requires further investigation. Besides HH with anosmia,
      there are isolated HH (IHH). No human GnRH mutations have been reported although
      hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic
      HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations
      have been described which represent about 50% of familial cases. The clinical
      features are highly variable and there is a good relationship between genotype
      and phenotype. A complete loss of function is associated with the most severe
      phenotype with resistance to pulsatile GnRH treatment, absence of puberty and
      cryptorchidism in the male. In contrast, milder loss of function mutations causes
      incomplete failure of pubertal development. The preponderant role of GnRH in the
      secretion of LH by the gonadotrophs explains the difference of the phenotype
      between male and female with partial GnRH resistance. Affected females can have
      spontaneous telarche and normal breast development while affected males exhibit
      no pubertal development but normal testis volume, a feature described as "fertile
      eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another
      gene, called GPR54, responsible for idiopathic HH has been recently described by
      segregation analysis in two different consanguineous families. The GPR54 gene is
      an orphan receptor, and its putative ligand is the product of the KISS-1 gene,
      called metastine. Their roles in the function of reproduction are still unknown.

PMID- 15146965
TI  - Influence of vitamin B6 supplementation on polyunsaturated fatty acids
      concentration in serum and liver of rats fed a diet restricted in protein.
AB  - The influence of vitamin B6 on fatty acids content in serum and liver of rats
      receiving low protein diets was studied. Addition of B6 decreased linoleic acid
      (LA) and increased alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) in
      serum of rats fed a protein-deficient diet (9% energy from proteins) for 3
      months. Further restriction of dietary protein (4.5% of energy from protein)
      caused an increase of the DHA concentration and sum of polyunsaturated fatty
      acids (PUFAs). In the liver of undernourished rats significant changes of PUFA
      composition were noticed, although without any significant influence of vitamin
      B6.

PMID- 15146966
TI  - Autoproteolysis rate of rainbow trout muscle proteins.
AB  - Effect of some physicochemical agents (pH, temperature and incubation time) and
      iced storage of farmed rainbow trout (Oncorhynchus mykiss) on autoproteolysis of
      muscle proteins and quality (sensory assessment, instrumental texture, total
      bacterial counts) were determined. The results showed that the autoproteolysis
      rate proceeded with its highest intensity at pH 4.2 and temperature about 55
      degrees C. The rate of protein hydrolysis and protease activity, as well as
      microbial contamination, gradually increased with prolonged periods of iced
      storage of fish. Properly iced trout immediately after its evisceration was
      acceptable in quality for up to 10 days.

PMID- 15146967
TI  - Changes of chemical composition and dough rheology in two fractions of sieve
      classified Polish spring wheat flour.
AB  - The study of chemical composition and dough rheology changes in sieve-classified
      two fractions (up to 60 and 60-240 microm particles) of wheat flour was the
      subject of this study. The straight grade flours were obtained by the milling of
      three Polish varieties of spring wheat, differing in particle size index (PSI)
      values. The flours were separated with the use of an SZ-1 laboratory sifter. The
      yield of fine fraction was in the range 50.0-55.7%. The obtained fractions were
      assayed for the content and composition of free lipids, gluten proteins, damaged
      starch, ash, water absorption and amylograph viscosity. Dough rheology (extrusion
      in OTMS cell, alveograph and farinograph tests) and baking trials were also
      performed. The content of free lipids, including the non-polar and phospholipids
      was lower and the content of glycolipids was higher in fine flours. Those
      fractions were more rich in linoleic acid but the lower content of oleic and
      linolenic acids resulted in a higher oxidizability index of free lipids. Fine
      flours contained less ash and significantly more damaged starch. At the same
      time, they were characterized by a higher content of wet gluten, water
      absorption, amylograph viscosity and better dough parameters. This was reflected
      in the bread volume, which was higher by 6.3-10.7%. The influence of the changes
      in composition and the content of free lipids upon the rheology of the dough
      after the 90 days flour storage has not been defined unambiguously and requires
      further research.

PMID- 15146968
TI  - Nutritional value of broad bean seeds. Part 3: Changes of dietary fibre and
      starch in the production of commercial flours.
AB  - We report on the impact of flour production from small- and large-seed varieties
      of broad bean on the quantitative and qualitative distribution of dietary fibre
      and starch. The experimental material consisted of the seeds of small-seed
      varieties of broad bean: Gobik and Goral, large-seed varieties of broad bean:
      Windsor Bialy and Bartom, and pea seeds of Albatros, Karat and Miko varieties
      (for comparison). The seeds were at full physiological maturity. Soaking and
      hydrothermal processing were shown to cause multidirectional, statistically
      significant changes in dietary fibre and starch, depending on both parameters of
      the process and type of the seeds. The flours of both small-seed broad bean
      varieties contained 20.15%-28.31%, flours of the large-seed broad bean 23.10%
      27.50%, and those from pea seeds 20.13%-22.81% total dietary fibre. Attention
      should be paid to the considerable, approximately 2-fold increase in the soluble
      dietary fibre (SDF) content, compared to the raw material. The processing of
      seeds caused significant changes also with reference to starch. The most
      considerable changes were observed when the variant with the longest times of
      soaking (18 h) and heating (45 min) was applied. In the broad bean flours, the
      content of analytically available starch decreased by 22.94-30.60% and its
      digestibility was observed to decrease up to 30.25%. The pea flours, however,
      were characterised by an increased concentration of both forms of starch,
      especially significant for the digestible starch. The calculated content of
      resistant starch (RS) differentiated, to a high extent, the flours obtained.
      Under the same processing conditions, the flours of small-seed Gobik and Goral
      varieties of broad bean were characterised by a significantly higher RS content
      than those obtained from the large-seed varieties. A decrease in the starch
      digestibility rate index (SDRI) values, especially high for the small-seed
      varieties, should also be emphasised. The results obtained indicate that the
      nutritional value of flours can be determined by controlled processing
      parameters.

PMID- 15146969
TI  - Influence of bioflavonoids from the radix extract of Scutellaria baicalensis on
      the level of serum lipids, and the development of laboratory rats fed with fresh
      and oxidized fats.
AB  - The aim of this study was to assess the influence of bioflavonoids from the radix
      of Scurellaria baicalensis on the level of lipids, via the determination of the
      concentrations of triglycerides, total cholesterol and high-density lipoprotein
      (HDL) cholesterol in the plasma of laboratory rats fed high-fat and high
      cholesterol diets, and via the calculation of their atherogenic index. We also
      studied the influence of bioflavonoids on their physical development by measuring
      the increase in their body mass and liver mass. The rats were fed a diet with a
      15% content of fresh or oxidized lard or sunflower oil, along with 0.5% added
      cholesterol. 0.05% S. baicalensis radix extract was added to the diet of half of
      the rats as the source of bioflavonoids. In the group of rats fed a diet
      containing oxidized oil we observed a significantly lower increase in body mass
      (15.5 +/- 7.6 g/4 weeks/rat) than that observed for the control rats (77.0 +/-
      15.7 g/4 weeks/rat). The addition of S. baicalensis radix extract to the diet
      raised the increase in body mass in the groups receiving oil as the source of
      fat; those receiving fresh oil had a 40% increase, and those receiving oxidized
      oil showed a 300% increase relative to the appropriate controls. In all the
      groups of rats fed a diet with bioflavonoids added, a beneficial decrease in the
      plasma triglyceride content was observed relative to the appropriate controls. In
      the plasma of rats on a diet containing the extract and fresh or oxidized oil or
      fresh lard, we observed a beneficial reduction in the total cholesterol level
      relative to the appropriate controls. The atherogenic index was higher for the
      group of animals fed with fresh lard than for those fed with fresh oil, and
      higher for those fed with oxidized oil than for those fed with oxidized lard. The
      addition of bioflavonoids to the diet beneficially reduced the atherogenic index
      value in the group fed with fresh oil, and increased its value in the group fed
      with oxidized lard.

PMID- 15146971
TI  - Moisture sorption characteristics of rice flour.
AB  - Moisture equilibrium data (adsorption and desorption) of rice flour were
      determined using the static gravimetric method of saturated salt solutions at
      three storage temperatures: 10, 20 and 30 degrees C. The range of water
      activities for each temperature was from 0.11 to 0.85. Equilibrium moisture
      content decreased with increase in storage temperature at any given water
      activity. The experimental data were fitted to four mathematical models (modified
      Oswin, modified Halsey, modified Chung-Pfost and modified Henderson). The
      monolayer moisture content was estimated from sorption data using the Brunauer
      Emmett-Teller (BET) equation. The isosteric heats of sorption were evaluated
      using Clausius-Clapeyron equation.

PMID- 15146970
TI  - Effect of acetylation and succinylation on solubility profile, water absorption
      capacity, oil absorption capacity and emulsifying properties of mucuna bean
      (Mucuna pruriens) protein concentrate.
AB  - Mucuna protein concentrate was acylated with succinic and acetic anhydride. The
      effects of acylation on solubility, water absorption capacity, oil absorption
      capacity and emulsifying properties were investigated. The pH-dependent
      solubility profile of unmodified mucuna protein concentrate (U-mpc) showed a
      decrease in solubility with decrease in pH and resolubilisation at pH values
      acidic to isoelectric pH (pH 4). Apart from pH 2, both acetylated mucuna protein
      concentrates (A-mpc) and succinylated mucuna protein concentrate (S-mpc) had
      improved solubility over the unmodified derivative. Acylation increased the water
      absorption capacity (WAC) at all levels of ionic strength (0.1-1.0 M). WAC of the
      protein samples increased with increase in ionic strength up to 0.2 M after which
      a decline occurred with increase in ionic strength from 0.4-1.0 M. When protein
      solutions were prepared in salts of various ions, increase in WAC followed the
      Hofmeister series in the order: NaSCN < NaClO4 < NaI < NaBr < NaCl < Na2SO.
      Acetylation improved the oil absorption capacity while the lipophilic tendency
      reduced the following succinylation. Emulsifying capacity increased with increase
      in concentration up to 2, 4 and 5% w/v for U-mpc, A-mpc and S-mpc, respectively,
      after which an increase in concentration reduced the emulsifying capacity. Both
      acetylation and succinylation significantly (P < 0.05) improved the emulsifying
      capacity at pH 4-10. Initial increase in ionic strength up to 0.4 M for U-mpc and
      0.4 M for A-mpc and S-mpc increased the emulsion capacity progressively. Further
      increase in ionic strength reduced emulsion capacity (EC). Contrary to the effect
      of various salts on WAC, increase in EC generally follows the series Na2SO4 <
      NaCl < NaBr < NaI < NaClO4 < NaSCN. At all levels of ionic strength studied, S
      mpc had a better emulsifying activity (EA) than both A-mpc and U-mpc. EA and
      emulsifying stability (ES) were pH-dependent. Maximum EA and ES were recorded at
      pH 10. ES of protein derivatives were higher than those of U-mpc in the range of
      pH 4-10 but lower at pH 2. Studies revealed that both A-mpc and S-mpc had better
      ES and EA than the unmodified derivative when protein solutions were prepared in
      salts of various anions.

PMID- 15146972
TI  - Wheat flour confectionery products as a source of inorganic nutrients: zinc and
      copper contents in hard biscuits.
AB  - Cereal-based confectionery products being consumed through whole human life are
      considered mainly to be a source of carbohydrates, that is energy, although
      cereals are a rich source of minerals as well. To evaluate some hard biscuits
      produced in Croatia as a source of different trace elements in nutrition, in this
      study Zn and Cu contents were determined in classic wheat flour biscuits and in
      dietetic biscuits enriched with whole wheat grain flour or whole wheat grain
      grits, soya flour and skimmed milk. Zn was determined by flame atomic absorption
      spectrometry (AAS); Cu was determined by inductively coupled plasma atomic
      emission spectroscopy (ICP-AES). The results show that the Zn content in
      different kinds of biscuits ranges from 5.89 up to 17.64 mg/kg and the Cu content
      ranges from 1.15 up to 2.79 mg/kg depending on the type of wheat milling products
      and mineral content of other ingredients used. Enriched dietetic biscuits
      produced from wheat flour type 850 and whole wheat grain flour and/or soya flour
      and skimmed milk were almost 200% and 150% higher in Zn and Cu, respectively, in
      comparison to classic white wheat flour biscuits and can be considered as good
      sources of Zn and Cu in nutrition.

PMID- 15146973
TI  - Mode of action of lactococcin R produced by Lactococcus lactis R.
AB  - We investigated the mode of action and factors affecting adsorption of
      lactoccocin R produced by Lactococcus lactis R. It was found that lactococcin R
      adsorbed to all Gram-positive but not to the Gram-negative bacteria tested and
      its adsorption was dependent on pH. It was observed that the binding of
      lactococcin R was prevented by anions of several salts (Cl-, PO4(-3)) and
      lipoteichoic acid. Pretreatments of sensitive cells and cell walls with
      detergents, organic solvents or enzymes did not reduce subsequent binding of
      lactococcin R. However, treatment of cell wall preparations with
      methanol:chloroform and hot 20% trichloroacetic acid (TCA) caused such walls to
      lose their ability to adsorb lactococcin R. Sensitive cells treated with
      lactococcin R lost high amounts of intracellular K+ ions, UV-absorbing materials
      and became more permeable to o-nitrophenol-beta-D-glactopyranoside (ONPG). In
      addition, different lactococcin R concentrations (0-2560 AU/mL) decreased the
      colony counts of Listeria monocytogenes by 99% and also a reduction in the
      absorbance values. These results show that the mode of action of lactococcin R is
      bactericidal rather than bacteriostatic.

PMID- 15146974
TI  - Sensory and rheological properties of transgenically and chemically modified
      starch ingredients as evaluated in a food product model.
AB  - Starches derived from five genetically modified potato lines, two chemically
      modified potato starches and two native starches from potato and maize were
      subjected to physical and chemical analyses and their functionality evaluated in
      a milk-based food product model. The transgenic starches were specifically
      modified with respect to amylopectin chain length and phosphorous content by
      suppression of the starch branching enzyme and overexpression of glycogen
      branching enzyme. Transgenic starches with long amylopectin chains and high
      phosphorous content had increased gelatinisation temperatures, produced gels with
      a higher tendency to retrograde and a low freeze/thaw stability as compared to
      starches with shorter amylopectin chains and lower phosphorous content. The
      textural properties of the food product model prepared from genetically and
      chemically modified starches were characterised by sensory and rheological
      analyses. To clearly visualise the effects of the modifications, data was
      evaluated by radar plots and multiple regression analysis (chemometrics).
      Genetically modified potato starches with longer amylopectin chains and increased
      phosphorous content gave a more gelled and a shorter texture as compared to
      starches with shorter amylopectin chains and decreased phosphorous content.
      Acetylated and hydroxypropylated potato starches gave sticky and stringy
      textures. Correlations between rheology parameters and sensory parameters were
      found. The sensory parameter stringy/long could be predicted from the rheological
      data.

PMID- 15146975
TI  - Usage of enzymes in a novel baking process.
AB  - In this study, the effects of different enzymes (alpha-amylase, xylanase, lipase,
      protease) on quality of breads baked in different ovens (microwave, halogen lamp
      microwave combination and conventional oven) were investigated. It was also aimed
      to reduce the quality problems of breads baked in microwave ovens with the usage
      of enzymes. As a control, bread dough containing no enzyme was used. Specific
      volume, firmness and color of the breads were measured as quality parameters. All
      of the enzymes were found to be effective in reducing the initial firmness and
      increasing the specific volume of breads baked in microwave and halogen lamp
      microwave combination ovens. However, in conventional baking, the effects of
      enzymes on crumb firmness were seen mostly during storage. The color of protease
      enzyme added breads were found to be significantly different from that of the no
      enzyme and the other enzyme added breads in the case of all type of ovens.

PMID- 15146976
TI  - Purine nucleosides support the neurite outgrowth of primary rat cerebellar
      granule cells after hypoxia.
AB  - Mammalian neurons require a constant supply of oxygen to maintain adequate
      cellular functions and survival. Following sustained hypoxia during ischemic
      events in brain, the energy status of neurons and glia is compromised, which may
      subsequently lead to cell death by apoptosis and necrosis. Concomitant with
      energy depletion is the formation of the purine nucleoside adenosine, a powerful
      endogenous neuroprotectant. In this paper the effect of chemical hypoxia on cell
      survival and neurite outgrowth of primary cerebellar granule cells was
      investigated. Rotenone, a mitochondrial complex I inhibitor, induced a 30.4 +/-
      3.6% loss of viable cells and a 35.0 +/- 4.4% loss of neurite formation of
      cerebellar granule cells, which was partially restored by the addition of purine
      nucleosides adenosine, inosine and guanosine. Inosine had the most striking
      effect of 37.7 +/- 2.9% rescue of viability and 71.2 +/- 18.4% rescue of neurite
      outgrowth. Data confirm the suggested role of purine nucleosides for the neuronal
      regeneration of primary brain cells following hypoxic insult.

PMID- 15146977
TI  - Signals and receptors for the nuclear transport of TFIIIA in Xenopus oocytes.
AB  - The transcription factor IIIA (TFIIIA) is a zinc finger protein that binds to
      both 5S genes and 5S ribosomal RNA. In Xenopus oocytes it is predominantly
      associated with 5S rRNA and retained as storage particle (7S RNP) in the
      cytoplasm. In this study, we have mapped the nuclear localization signal (NLS)
      activity in TFIIIA both in vivo and in vitro. Two independent nuclear import
      signals localize to the zinc finger region of TFIIIA, which is in direct contact
      with 5S rRNA in the context of the 7S RNP. A systematic analysis of importin
      alpha variants in Xenopus reveals that only importin alpha1 and importin alpha2
      are expressed in a pattern similar to TFIIIA during Xenopus embryogenesis; the
      same two import adaptors interact specifically with TFIIIA in vitro. On the basis
      of these and our previous findings, we therefore propose that the massive amounts
      of TFIIIA which are produced in early stages of oogenesis are imported into the
      nucleus via interaction with importin alpha1 and alpha2. TFIIIA-induced synthesis
      of 5S rRNA then allows for the formation and nuclear export of the 7S RNP; the 7S
      RNP is retained in the cytoplasm due to NLS masking via 5S rRNA binding.

PMID- 15146978
TI  - Autophagic and apoptotic features during programmed cell death in the fat body of
      the tobacco hornworm (Manduca sexta).
AB  - Two major pathways of programmed cell death (PCD)--the apoptotic and the
      autophagic cell death--were investigated in the decomposition process of the
      larval fat body during the 5th larval stage of Manduca sexta. Several basic
      aspects of apoptotic and autophagic cell death were analyzed by morphological and
      biochemical methods in order to disclose whether these mechanisms do have shared
      common regulatory steps. Morphological examination revealed the definite
      autophagic wave started on day 4 followed by DNA fragmentation as demonstrated by
      agarose gel electrophoresis and TUNEL assay. By the end of the wandering period
      the cells were filled with autophagic vacuoles and protein granules of
      heterophagic origin and the vast majority of the nuclei were TUNEL-positive. No
      evidence was found of other aspects of apoptosis, e.g. activation of executioner
      caspases. Close correlation was disclosed between the onset of autophagy and the
      nuclear accumulation of the ubiquitin-proteasome system.

PMID- 15146980
TI  - Evidence that climate change has caused 'emergence' of tick-borne diseases in
      Europe?
AB  - Even though tick-borne disease systems are highly susceptible to climatic
      influences, climate change to date is not necessarily the cause of the marked
      increased incidence of a variety of tick-borne diseases in many parts of Europe
      over the past two decades. To test for causality, rather than coincidence, we
      need to examine whether the right sorts of climate change have occurred at the
      right time and in the right places to account for the observed heterogeneous
      temporal and spatial patterns of tick-borne disease 'emergence'. Tick-borne
      encephalitis (TBE) incidence, for example, showed a 3-fold step increase from
      1983 to 1986 in Sweden, doubled in 1993 in the Czech Republic, increased even
      more dramatically in the same year in Lithuania and Poland, but declined markedly
      in 1997 in Hungary, Croatia and Slovenia. Within each country, TBE incidence has
      changed to different degrees in different regions. Because other tick-borne
      diseases, notably Lyme borreliosis, has commonly 'emerged' in parallel with TBE,
      we should first examine climate variables predicted to have a general effect on
      tick abundance, which has indeed increased in the past decade. These include
      temperature and moisture stress, which have seasonally differential impacts.
      Monthly mean records for 1960-2000 from the UK Climate Research Unit's
      interpolated global climate surface reveal that mean spring, spring-autumn and
      winter temperatures have all increased gradually over the past 40 years, but
      apparently most sharply in the late 1980s, when moisture stress also increased.
      These climate data do not reveal any obvious differences between sites where TBE
      did or did not 'emerge', and in Sweden increases in TBE pre-dated the onset of
      warmer springs and winters. If recorded climate changes cannot yet satisfactorily
      explain the temporal and spatial patterns of tick-borne disease change in Europe,
      the impact of biotic factors, such as increases in deer abundance and changing
      habitat structure, and of socio-political changes following the end of communist
      rule, demand more detailed quantitative analyses.

PMID- 15146979
TI  - Apactin is involved in remodeling of the actin cytoskeleton during regulated
      exocytosis.
AB  - Apactin is an 80-kDa type I membrane glycoprotein derived from pro-Muclin, a
      precursor that also gives rise to the zymogen granule protein Muclin. Previous
      work showed that apactin is efficiently removed from the regulated secretory
      pathway and targeted to the actin-rich apical plasma membrane of the pancreatic
      acinar cell. The cytosolic tail (C-Tail) of apactin consists of 16 amino acids,
      has Thr casein kinase II and Ser protein kinase C phosphorylation sites, and a C
      terminal PDZ-binding domain. Secretory stimulation of acinar cells causes a
      decrease in Thr phosphorylation and an increase in Ser phosphorylation of
      apactin. Fusion peptides of the C-Tail domain pulldown actin, ezrin, and
      EBP50/NHERF in a phosphorylation-dependent manner. HIV TAT-C-Tail fusion peptides
      were used as dominant negative constructs on living pancreatic cells to study
      effects on the actin cytoskeleton. During secretory stimulation, TAT-C-Tail
      Thr/Asp phosphomimetic peptide caused an increase in actin-coated zymogen
      granules at the apical surface, while TAT-C-Tail-S/D phosphomimetic peptide
      caused a broadening of the actin cytoskeleton. These data indicate that
      stimulation-mediated Thr dephosphorylation allows decreased association of
      apactin with EBP50/NHERF and fosters actin remodeling to coat zymogen granules.
      Stimulation-mediated Ser phosphorylation increases apactin association with the
      actin cytoskeleton, maintaining tight bundling of actin microfilaments at the
      apical surface. Thus, apactin is involved in remodeling the apical cytoskeleton
      during regulated exocytosis in a manner controlled by phosphorylation of the
      apactin C-Tail.

PMID- 15146981
TI  - Global climate change and the emergence/re-emergence of infectious diseases.
AB  - Variation in the incidence of vector-borne diseases is associated with extreme
      weather events and annual changes in weather conditions. Moreover, it is assumed
      that global warming might lead to an increase of infectious disease outbreaks.
      While a number of reports link disease outbreaks to single weather events, the El
      Nino/Southern Oscillation and other large-scale climate fluctuations, no report
      unequivocally associates vector-borne diseases with increased temperature and the
      environmental changes expected to accompany it. The complexity of not yet fully
      understood pathogen transmission dynamics with numerous variables might be an
      explanation of the problems in assessing the risk factors.

PMID- 15146982
TI  - Human granulocytic ehrlichiosis in Europe.
AB  - Human granulocytic ehrlichiosis (HGE) is a tick-borne zoonosis caused by
      Anaplasma phagocytophilum. A MEDLINE literature search revealed that the European
      story of HGE began in 1995 with an article on the presence of serum antibodies to
      A. phagocytophilum. At present, there is seroepidemiological information
      indicating the presence of infection with HGE agent(s) for several European
      countries; seroprevalence rates range from zero or very low to up to 28%. The
      proportion of seropositive persons increases with age and is higher in persons
      exposed to ticks. Knowledge of the causative agent of HGE and of animal
      reservoirs in Europe is limited. Ixodes ricinus is a recognized vector of A.
      phagocytophilum in Europe. Prevalence of the agent in questing I. ricinus is
      usually higher in adult ticks than in nymphs and ranges from zero or very low to
      > 30%. Pronounced differences between countries and marked variability by
      localities were established. Up to March 2003 about 65 human patients (all but
      one were adults) with confirmed HGE and several patients fulfilling criteria for
      probable HGE had been reported. The majority of them came from Central Europe
      (Slovenia) and Scandinavia (Sweden) but there are individual reports from several
      other European countries. The patients presented with an acute febrile illness
      that as a rule occurred after a tick bite; the majority had leukopenia and/or
      thrombocytopenia, elevated concentration of C-reactive protein and mild
      abnormalities of liver function test results. A small number of patients does not
      permit reliable conclusions on the clinical features of European HGE; however,
      there is an impression that at least in central Europe (but maybe not in
      Scandinavia) the disease is, from the clinical angle, only mild to moderately
      severe and (most likely) self-limited. The relatively high proportion of the
      population with HGE serum antibodies and the presence of A. phagocytophilum
      (like) agent(s) in ticks, small mammals and deer as found in several European
      countries are discordant with the rather low number of patients with proven HGE.
      The discordance may indicate inadequate awareness among European physicians,
      limited recording and reporting of the disease, and/or the presence of and the
      infection of humans with nonpathogenic A. phagocytophilum (like) strains present
      in ticks. Additional studies are needed to better define the biological and
      public health significance of HGE in Europe.

PMID- 15146984
TI  - A tick-borne encephalitis ceiling in Central Europe has moved upwards during the
      last 30 years: possible impact of global warming?
AB  - The geographic/temporal pattern of cases of tick-borne encephalitis (TBE)
      registered in the Czech Republic since 1970 was analysed to verify the surmise of
      a global warming effect. Using a geographic information system, over 8,700
      notified places of infection were pin-pointed on a map and overlaid with a
      digital elevation model to estimate the vertical distribution of the cases.
      Series of yearly disease ceilings (assessed alternatively as the respective
      maximum altitude or mean altitudes of the upper 5 or 10 cases) were tested
      against the null hypothesis of random elevation course and analysed for
      correlation with concomitant factors (yearly TBE incidence rate, mean yearly
      temperature, population density of small rodents and roe deer). Statistical tests
      proved that the TBE ceiling has gradually moved upwards in the course of the last
      three decades. The average rate of ascension within this period was approx. 5.4
      +/- 1.7 m yearly, which corresponds well with concurrent mean temperature rising
      of approx. 0.036 +/- 0.007 degrees C yearly, and the vertical temperature
      gradient of 0.0065 +/- 0.0004 degrees C m(-1). The TBE-ceiling estimates
      significantly correlated with TBE-incidence data and the mean yearly temperature
      recorded 1-2 years earlier. Although TBE incidence correlated with rodent
      population density that was observed 1-2 years earlier, the TBE ceiling does not
      seem to be influenced by rodent population dynamics nor did the population
      dynamics correlate with mean yearly temperatures. TBE incidence as well as mean
      altitudes of the upper 10 cases also correlated with official data on harvested
      roe deer. Overall, the fluctuations of TBE incidence and TBE ceiling proved to be
      synchronous processes that correspond with temperature changes. Although the
      dependence of TBE on temperature is not a direct one and various factors could be
      involved, an impact of climate warming on the vertical disease distribution in
      Central Europe is evident.

PMID- 15146983
TI  - Vectors of tick-borne diseases and epidemiological situation in Latvia in 1993
      2002.
AB  - During the period of 1993-2002 an increase and the remarkable changes in the
      incidence of tick-borne encephalitis (TBE) and Lyme borreliosis (LB) as well as
      annual activities of vector species were noticed. The highest increase of TBE
      morbidity in Latvia has been observed in 1994 and 1995, and less expressed also
      in 1998 which was followed by a significant decrease during subsequent years.
      Whereas the highest peak of LB morbidity has been noticed in 1998 with only a
      minor decrease during subsequent years. Two epidemiologically significant Ixodes
      tick species are common in Latvia. Ixodes ricinus L. spread in the western and
      central part of Latvia; but rarely and in small numbers also in the eastern part.
      Ixodes persulcatus P. Sch. seems to dominate only in the eastern part of the
      country. The changes of seasonal and annual activities of I. ricinus were
      observed in two types of monitoring sites--sylvatic and peridomestic, located in
      the central part of Latvia. Observations of I. persulcatus were made in the
      eastern districts. Comparing geographically the Tick-borne diseases (TBD)
      incidence data for three tick distribution regions (I. ricinus dominated, I.
      persulcatus dominated and mixed regions), it was observed that the trend of
      annual changes in LB incidence during the last decade is almost of the same kind
      for all regions. Whereas TBE incidence extremes in 1994 and 1995 were observed
      almost only in I. ricinus dominated region. The annual field-collected adult tick
      infection rate with TBE virus (TBEV) from 1993 to 2002 for I. ricinus adults
      varied between 1.7% and 26.6% and for I. persulcatus--between 0% and 37.3%. The
      infection level in ticks removed from humans was much higher and from 1998 to
      2002 surpassed 30%. TBEV investigations of removed adults and nymphs in 2002
      discovered a high TBEV prevalence also in I. ricinus nymphs (43%). Typing of TBE
      virus isolated from ticks and patient serum samples in collaboration with German
      and Swedish virologists revealed that all three TBEV subtypes were co-circulating
      in Latvia. The mean annual tick infection rate with Borrelia burgdorferi s.l.
      analysed by means of a nested polymerase chain reaction of OspA gene fragment
      during the period of 1999-2001 was 18%-38% for I. ricinus adults and 25%-51% for
      I. persulcatus adults. Typing of Borrelia-positive DNA samples indicated that B.
      afzelii was dominant in Borrelia-positive I. ricinus (64.9%) and I. persulcatus
      (81.2%) followed by B. garinii (I. ricinus: 24.3%; in I. persulcatus: 14.5%).
      Investigations of Ehrlichia phagocytophila genogroup (by nested PCR targeted the
      16S rRNA gene) revealed the presence of Ehrlichia sp. in I. ricinus from the
      central part of Latvia. Obtained data on TBD vectors and the epidemiological
      situation during the last decade indicates the complex impact of different
      factors influencing TBE and LB morbidity in Latvia.

PMID- 15146985
TI  - An attempt to elucidate the increased incidence of tick-borne encephalitis and
      its spread to higher altitudes in the Czech Republic.
AB  - In 1993 the incidence of tick-borne encephalitis (TBE) showed a sharp rise in
      Central Europe and has remained high since--with some slight fluctuation. This
      increase is clearly evident in the Czech Republic and it could be roughly
      characterised as twofold in 1993-2001 in comparison with 1984-1992 (5,240:2,441
      human cases). As yet in the Czech Republic the TBE increase has been manifested
      by: a) higher number of cases in areas well known for TBE occurrence in humans;
      b) re-emergence in areas where TBE human cases were not observed, or only
      sporadically, for a long time; c) emergence of TBE in places unknown previously
      (including highly elevated areas). This phenomenon has not been fully elucidated
      yet and we would like to contribute to a better understanding of its cause by
      comparing the present situation with historical data. Besides TBE epidemiological
      data (1965-2001) we use the twenty-year all season dynamics data of Ixodes
      ricinus host-seeking activity (1953-1972) supplemented by the data in 1982, 1992
      and by meteorological data characterising periods under study. The fluctuation in
      annual averages of I. ricinus occurrence was irregular. These irregularities when
      compared with meteorological data can be explained by different meteorological
      conditions in particular years. In corresponding long-time series, the peaks of
      I. ricinus occurrence and TBE incidence were reached at the same time. Analyses
      of relevant meteorological data displayed that joint I. ricinus and TBE maximal
      occurrence values had been preceded by mild (or warm) autumn seasons allowing a
      prolongation of I. ricinus activities (including development) up to November at
      least, thus resulting in a higher tick volume the following year. Based on these
      data we conclude that the increased TBE incidence rates reported in 1993 and
      afterwards are attributable to a more abundant occurrence of I. ricinus ticks and
      that their higher abundance is due to modified climatic conditions in the last
      decade. Such a situation has appeared in the past as well; however, it was rare
      and in isolated years only. At that time, although the tick population had been
      more abundant, in the following year it reached the usual level again. In the
      1990s the prolonged mild autumn for consecutive several years led to permanently
      more abundant populations of I. ricinus. The same conclusion explains the shift
      of I. ricinus occurrence and of TBE distribution to higher altitudes in Sumava
      and Krkonose Mountains.

PMID- 15146986
TI  - Socio-economic conditions and other anthropogenic factors influencing tick-borne
      encephalitis incidence in the Czech Republic.
AB  - Laboratory confirmed cases of tick-borne encephalitis (TBE) have been reported in
      the Czech Republic since 1971. Peaks of incidence occurred at 2 to 5-year
      intervals. The incidence in the eighties was generally lower than in seventies.
      In the nineties there was a sharp increase in incidence that peaked in 1995
      (7.2/100,000). TBE cases occur from April to November with maximum incidence in
      July. During the last decade the second peak of incidence occurred in most years
      in September and/or October. In the last decade, an extension of the TBE season
      towards the spring and autumn periods has been observed. In addition to a general
      increase in TBE incidence in the last decade, some other changes in the
      epidemiology of TBE were observed in the Czech Republic. During the whole period
      sex-specific incidence was higher in men than in women (men to women ratio
      1.5:1). Age-specific incidence over recent years increased steadily in children
      and adolescent age groups. In the ten-year age groups from 25 to 65, it remains
      practically at the same level (6-8/100,000). In older persons it fell to 2
      3/100,000. Tick bites infect patients mainly during their recreational
      activities. A very small proportion (less than 1%) acquires the infection through
      the alimentary route. We have tested the hypothesis whether the increase in TBE
      incidence in the nineties was due to economical or social changes after the
      velvet revolution of 1989. Between 1991 and 1995 unemployment largely remained on
      the same level (between 2-3%). Over the next years the percentage of unemployed
      persons increased rapidly to 9.3% in 1999 (7.8% in 2001). This trend differs
      significantly from the trend of TBE incidence that peaked in 1995. No correlation
      between the district incidence of TBE and the district percentage of unemployment
      in the years 1997-2001 was found (r=-0.20). The percentage of unemployed persons
      among the TBE cases was 1-3% in contrast to the Czech Republic figures which were
      5-9% for the same period. The gross domestic product in USD per capita increased
      from dollars 2,600 in 1991 to dollars 5,000 in 1995. Since then it has varied
      between dollars 4,800 and dollars 5,600. This trend, therefore, differs from the
      trend of TBE incidence as well. Among the TBE cases the percentage of foresters
      and other persons working in the forests in the years 1997-2001 was 0.5-1%. The
      behavioral and socio-economic aspects of TBE cases remained stable despite the
      political changes which have take place in the Czech Republic since the beginning
      of the nineties. They are not, therefore, responsible for the increased TBE
      incidence. In the industrial areas most polluted by SO2 in the past in northern
      Bohemia the sharp increase in TBE incidence seems to be connected with measures
      aiming to eliminate SO2 emissions from brown coal power stations.

PMID- 15146987
TI  - Tick-borne encephalitis (TBE) in Germany--epidemiological data, development of
      risk areas and virus prevalence in field-collected ticks and in ticks removed
      from humans.
AB  - In Germany, 100-300 autochthonous clinical TBE cases have been recorded annually.
      There are high-risk areas in Bavaria and Baden-Wuerttemberg and ongoing low-risk
      areas in Hesse, Thuringia, and the Rhineland-Palatinate and single cases in
      Saxony. In order to be able to evaluate the epidemiological changes described
      here, it must be mentioned that a new definition of TBE risk areas was introduced
      on the district level in 1998 in Germany and in 2001 with the new Infection
      Protection Act (Infektionsschutzgesetz) which states that TBE is a notifiable
      disease. This led to the replacement of earlier surveillance systems and to many
      changes to data collection. In 1998 63 country and town districts were TBE risk
      areas, in 2001 79 and in 2002 86. There were new risk districts within Bavaria
      and Baden-Wuerttemberg and outside these regions in Thuringia, Hesse and the
      Rhineland-Palatinate. An interesting trend was observed in TBE epidemiology. The
      TBE incidence in Bavaria and Baden-Wuerttemberg has been stable on a high level
      for years; outside these areas it has steadily been climbing (Odenwald,
      Thuringia). On the basis of epidemiological data on TBE from the eastern part of
      Germany since 1960, it is obvious that major changes in virus activity in TBE
      risk areas also occurred in the past, the explanation of which has remained a
      matter for speculation. The epidemiological situation in the different risk areas
      for TBE in Germany was found to vary considerably, if one considers the
      surveillance data of the last 40 years. 1. Establishment of completely new low
      risk areas. 2. Reactivation of formerly active areas with endemic latency. 3.
      High-risk areas with stable viral activity over long periods. 4. High-risk areas
      which have expanded and merged with low-risk areas. 5. High-risk areas which have
      developed into endemic areas or become inactive. High-risk TBE areas from 1960
      1975 (i.e. Mecklenburg-Western Pomerania) have since completely disappeared.
      There were, at the same time, high-risk areas in Thuringia which had only become
      latent and have now obviously become active again. The Odenwald demonstrated
      growing virus activity in the 1990s. These changes in TBE activity in German risk
      areas over more than the last 40 years are presented schematically. This ongoing
      number of risk areas is certainly linked to the notification obligation and
      greater public awareness. Nevertheless, any effects of ecological and climatic
      changes on the natural foci cannot be ruled out nor can changes in human leisure
      behaviour. Local weather conditions also have a major effect on the TBE
      incidence. Warm and dry summers may cause low tick activities, rainy summers may
      lead to low exposure rates of human beings. Even changes in forms of agricultural
      production prompted by different political structures probably have an impact as
      do economic constraints which may lead to lower vaccination and higher exposure
      rates. Regular, systematic virus prevalence measurements from 1997 to 2002 in
      field-collected ticks in German high-risk areas do not indicate any risk increase
      nor do they suggest a downward trend. Studies on virus prevalence in questing
      versus partially engorged ticks indicate that we neither exactly know nor
      understand the real quantitative relations between the virus and the host. In a
      first study, virus prevalence in Ixodes ricinus removed from humans was examined.
      Humans which were exposed in some districts near Passau in Bavaria. In the autumn
      of 2001, virus prevalence of unengorged free-living nymphs (n = 820) in this area
      was 0.38 (0.08-1.1)% and of adults (n = 90) 1.17 (0.03-6.38)%. Surprisingly,
      virus prevalence in partially engorged ticks from the same area collected during
      the same period was significantly higher (nymphs, n = 86, 6.9% and adults, n =
      129, 9.3%). Virus-positive partially engorged ticks were only found in districts
      known as risk areas. Nucleotide and deduced amino acid sequence data of the PCR
      products have confirmed the presence of virus prototype Neudoerfl only.

PMID- 15146988
TI  - Problems in the study and prophylaxis of mixed infections transmitted by ixodid
      ticks.
AB  - The spread of mixed infections with natural focality transmitted by ixodid ticks
      is a normal phenomenon attributable to trends in the relationships of different
      pathogens in the vector organism and ecosystem as a whole. Any disease developing
      as a result of tick bite should be regarded as a potentially mixed infection.
      Clinically, tick-borne mixed infections proceed more severely than the
      corresponding diseases caused by a single agent. The residual course of the
      disease may sometimes be accounted for by the persistence of two or even several
      pathogens. This implies the necessity of a comprehensive approach to the study,
      diagnosis, treatment, management and prophylaxis of infections belonging to this
      group.

PMID- 15146989
TI  - Pathogens and symbionts in ticks: prevalence of Anaplasma phagocytophilum
      (Ehrlichia sp.), Wolbachia sp., Rickettsia sp., and Babesia sp. in Southern
      Germany.
AB  - Tick-transmitted diseases like tick-borne encephalitis and Lyme borreliosis have
      been well known in Germany for decades. Ongoing research now gives an additional
      focus to a broad range of other bacteria and parasites in ticks like Anaplasma
      phagocytophilum, former Ehrlichia sp., Rickettsia sp. and Babesia sp. Knowledge
      about the prevalence of these infectious agents in ticks is an important
      prerequisite for risk assessment of human diseases. Therefore nymphs and adult
      Ixodes ricinus ticks were collected and examined for Anaplasma phagocytophilum (n
      = 5424 ticks), Rickettsia sp. (n = 1187), and Babesia sp. (n = 3113). For the
      detection of Anaplasma phagocytophilum, DNA from the 16S rDNA gene was amplified
      by nested PCR and hybridized with a DIG-labeled oligonucleotide probe. The
      examination of Rickettsia sp. was performed by single PCR. A partial sequence of
      the citrate synthase gene was amplified. As a target for the detection of Babesia
      sp., DNA from the 18S rDNA gene was amplified, also by single PCR. All positive
      PCR products were sequenced to control specificity. Anaplasma phagocytophilum was
      detected by PCR in n = 103 (1.9%) out of 5,424 examined ticks from 11
      investigation areas. However, not all positive PCR products hybridized using DIG
      labeled oligonucleotide probe. Thus, the result of sequencing indicated that only
      1.0% (n = 54) belonged to Anaplasma phagocytophilum and nearly half of these PCR
      products (0.9%) were identified as Wolbachia sp. Rickettsia sp. in Ixodes ricinus
      ticks from 3 areas were found in n = 105 (8.9%) out of 1,187 ticks examined
      (range from 13.3% to 5.6%). Sequencing showed Rickettsia helvetica exclusively.
      In about 2.6% of Rickettsia-positive ticks, double infection with Anaplasma
      phagocytophilum was found. Babesia sp. was detected in n= 31 (1.0%) out of 3,113
      ticks examined, which originated from 4 different areas. By sequencing, n = 28
      (90.0%) were identified as Babesia divergens. Three of all Babesia-positive ticks
      were identified as harboring Babesia microti. The detection of Anaplasma
      phagocytophilum, Rickettsia sp. and Babesia sp. demonstrates their possible role
      as a source of human infection in Germany.

PMID- 15146990
TI  - Zoonotic Babesia: possibly emerging pathogens to be considered for tick-infested
      humans in Central Europe.
AB  - The three host-tick Ixodes (I.) ricinus is regarded as an important vector of
      tick-borne microorganisms pathogenic for humans in central Europe and is
      primarily known as the main vector of Borrelia (B.) burgdorferi and the virus
      causing tick-borne encephalitis (TBE), the most clinically relevant tick
      transmitted pathogens for humans in European countries. Furthermore, it is now
      well established that I. ricinus also transmits Ehrlichia (E.) phagocytophila,
      Babesia (Ba.) divergens, and Ba. microti, all agents of zoonotic infections in
      dear, sheep, cattle, dogs, and horses. In addition to their known zoonotic
      potential, recent molecular-epidemiological and seroepidemiological surveys as
      well as increasingly reported clinical cases of infections caused by these tick
      borne organisms other than B. burgdorferi (TOBB) also strongly suggest a possible
      relevance of Babesia, Ehrlichia and Rickettsia for humans at risk in Europe.
      However, there are few medical microbiological investigations and epidemiological
      data on the distribution and relevance of Babesia for humans in our part of the
      northern hemisphere. There is also very little diagnostic and clinical knowledge
      on human babesiosis in many regions of Europe. Furthermore, sophisticated
      diagnostic tools designed for the reliable detection of the underlying pathogens,
      are not yet generally available to the microbiological laboratory. This review
      aims to provide basic information on human babesiosis and the most relevant
      causative pathogens of the disease in Europe and to draw attention to this
      parasitic infection as a possibly emerging and probably under-diagnosed disease
      in this part of the northern hemisphere.

PMID- 15146992
TI  - Lyme borreliosis spirochetes in questing ticks from mainland Portugal.
AB  - In Portugal, Ixodes ricinus ticks have been shown to contain DNA of several
      spirochetes belonging to the Borrelia burgdorferi sensu lato complex, with major
      differences in the genetic diversity between ecozones. Some isolates have been
      obtained since 1999, confirming the circulation of pathogenic strains in these
      ticks. Ixodes ricinus is considered to be a widespread species, however, in
      Portugal it is found only in a few habitats. Here we present preliminary results
      from a nationwide survey of questing I. ricinus (n = 4,001) and other Ixodidae (n
      = 1,534) in Portugal, initiated in 2001. The sampling points (so far 41) were
      selected using a Geographic Information System, according to the type of
      vegetation, accessibility and prevalence of human cases. The spatial and temporal
      of tick abundance and the infection of B. burgdorferi sensu lato in ticks were
      determined in selected areas. Ticks were examined for the presence of B.
      burgdorferi sensu lato by culturing (719 out of 4,001 I. ricinus), and direct PCR
      amplification of the 5S-23S intergenic spacer region (1,870 out of 5,535)
      followed by RFLP analysis, the reverse line blot assay and nucleotide sequencing
      of PCR amplicons. The most abundant tick genus was Rhipicephalus (53%), followed
      by Dermacentor (34%), I. ricinus and Hyalomma (7%, each). The Mafra and Grandola
      sites, where a more intensive study was carried out, were excellent habitats for
      I. ricinus. However, a clear difference of the prevalence of Borrelia infection
      and the genetic diversity of circulating spirochetes was observed in these two
      sites. Genotyping of all I. ricinus isolates revealed 5 B. garinii, 8 B.
      lusitaniae and 1 B. valaisiana strains, which were obtained for the first time in
      these regions along with a considerable percentage of tick-derived PCR amplicons.
      Two hard-tick species other than I. ricinus in Grandola were also B. lusitaniae
      positive, thus seeming to take part in the transmission cycle of Borrelia. The
      seasonal dynamics of I. ricinus in Mafra was bimodal, more pronounced in nymphs
      than in adults. The present findings indicate that B. burgdorferi sensu lato
      agents are differentially maintained in nature in local tick populations in
      different geographic areas across Portugal and that the risk of acquiring Lyme
      borreliosis in certain areas of Portugal is higher than previously assumed.

PMID- 15146991
TI  - First report on the coexistence and compatibility of seven tick-borne pathogens
      in unfed adult Ixodes persulcatus Schulze (Acarina: Ixodidae).

PMID- 15146993
TI  - Increased expression of Borrelia burgdorferi factor H-binding surface proteins
      during transmission from ticks to mice.
AB  - The spirochete Borrelia burgdorferi is transmitted to humans and other warm
      blooded animals through the bites of infected Ixodes species ticks. Our studies
      indicate that these spirochetes utilize a quorum sensing mechanism to control
      protein expression patterns that involves the chemical signal autoinducer-2 (AI
      2). Through this mechanism, a population of Lyme disease spirochetes may
      synchronize production of proteins needed for infection processes. AI-2 is
      produced by the B. burgdorferi LuxS protein, which we have demonstrated to be a
      functional enzyme. It has also been previously reported that luxS message is
      upregulated in feeding nymphal ixodid ticks. Among the B. burgdorferi proteins
      regulated through AI-2 are the complement inhibitory factor H binding Erp
      lipoproteins. We now report Erp protein expression is also increased during
      transmission of B. burgdorferi from nymphal ticks to mammalian hosts. Essentially
      no B. burgdorferi within unfed nymphal ticks expressed Erps, while almost all
      transmitted bacteria were Erp positive. These studies suggest that B. burgdorferi
      within feeding nymphal ticks produce AI-2 to coordinate expression of mammalian
      infection associated proteins, such as the factor H binding Erp lipoproteins.
      Binding of mammalian host factor H by Erps may then help promote bacterial
      dissemination through host tissues.

PMID- 15146995
TI  - TBE booster immunization in adults--first experience with a new tick-borne
      encephalitis (TBE) vaccine, free of protein-derived stabilizer.
AB  - A total of 222 adult subjects, all of whom received primary immunization
      according to the rapid immunization schedule in a preceding clinical trial with
      either a new (i.e. polygeline free) or formerly licensed (i.e. polygeline
      containing) TBE vaccine were invited for extension studies. The subjects received
      the first booster immunization with the new TBE vaccine at 12 to 18 months after
      primary immunization. Subsequently, a total of 191 of the 222 subjects could be
      enrolled in a serological follow-up one year after the booster immunization.
      Neutralizing TBE antibody titers were determined prior to, 21 days after and
      approximately 12 months after booster immunization. Prior to first booster
      immunization, TBE antibodies (GMTs) had remained on a high level and were far
      above the detection limit of the neutralization test used. All subjects of the
      per protocol population who were primarily immunized with the new TBE vaccine
      formulation and all but one subject of the control group were still seropositive
      prior to the booster. All subjects showed a sharp increase of TBE antibodies
      following the booster immunization. Within the 12 months follow-up period,
      neutralizing TBE antibody titers remained on a high level. The booster
      vaccination was well tolerated by the subjects. Only very few febrile reactions
      (< 1%) none higher than 38.5 degrees C were reported. No serious or unexpected
      adverse events related to vaccination were reported. These successful results in
      terms of both immunogenicity and safety indicate that TBE vaccination with this
      new TBE vaccine can be used safely in adults. A long lasting immunity can be
      concluded from the strong immune response following the booster immunization.

PMID- 15146994
TI  - Long-term immunity after vaccination against tick-borne encephalitis with Encepur
      using the rapid vaccination schedule.
AB  - 148 of 157 invited adult subjects who had participated in previous studies were
      enrolled in this extension study for evaluation of immunogenicity and safety of
      the second TBE booster immunization. All subjects had been previously immunized
      in studies with Chiron's formerly marketed TBE vaccine (containing polygeline as
      the stabilizer) according to the rapid vaccination schedule (i.e. primary
      immunization on days 0, 7, 21 and first booster immunization at month 15). All
      subjects were administered the second booster with Chiron's new TBE vaccine,
      which is free of protein-derived stabilizers, 36 months after the first booster
      vaccination applied at study month 15. Blood samples were taken prior to booster
      and 1 month later. In 145 out of 148 subjects, blood samples suitable for
      measurements of TBE antibodies (ELISA assay) were provided. Prior to second
      booster immunization with Chiron's new TBE vaccine, TBE antibodies (GMTs) had
      remained at a high level and were far above the detection limit of the used ELISA
      test. All subjects were still seropositive prior to the second booster
      immunization. The second booster immunization resulted in a further increase of
      TBE antibodies. The booster vaccination with Chiron's new TBE vaccine was well
      tolerated by all the vaccinees. Neither febrile post-immunization reactions nor
      unexpected adverse events or serious adverse events were reported. To summarize,
      these data clearly show that the TBE vaccination with this new TBE vaccine can be
      used safely to boost subjects pre-immunized with the former TBE vaccine
      formulation. Long-lasting immunity following this second TBE booster immunization
      can be concluded.

PMID- 15146996
TI  - Stimulation of the immune system by different TBE-virus vaccines.
AB  - Tick-borne encephalitis (TBE) is one of the most frequent arthropod-transmitted
      viral diseases in Europe. Different vaccines against TBE-virus have been
      developed; a thimerosal-free and also albumin-free vaccine [Ticovac (Baxter
      Hyland Immuno, Vienna)] was approved in 2000. Contrary to previous experience,
      779 cases of fever occurred following the first vaccination of children under 15
      years of age and in 62 children febrile convulsions were even observed.
      Consequently, the composition of the vaccine was changed and albumin was again
      added [FSME-Immun (Baxter Vaccines, Vienna)] in 2001. The new Encepur Kinder
      (Chiron-Behring, Marburg) from 2002 is a TBE-vaccine for children without any
      protein as stabilizer but with a relatively high concentration of sucrose, while
      the former vaccine Encepur K from 1991 contained polygeline as the stabilizer.
      The induction of the immune system by the different TBE virus vaccines was
      compared in an in vitro test in order to find an explanation for the unexpected
      fever attacks. Whole blood was stimulated with complete vaccine suspension, and
      TNF-alpha, IL-1beta, IL-6, and IL-8 were determined from heparin/EDTA-plasma and
      culture supernatants. It was shown that Ticovac and the new Encepur Kinder can
      induce relatively high amounts of TNF-alpha and lower amounts of IL-1beta. An
      increase of both cytokines was first observed following an incubation of 4 hours,
      with a maximum after 15 hours. Concentrations returned to base-line values within
      26 hours. The behaviour of both cytokines correlates with the febrile phases in
      children up to two years old. Albumin or other proteins like polygeline and also
      immunoglobulins prevented a rise of cytokines.

PMID- 15146997
TI  - State-of-the-art serological techniques for detection of antibodies against tick
      borne encephalitis virus.
AB  - Indirect immunofluorescence, ELISA and immunoblot test systems for the detection
      of antibodies against tick-borne encephalitis (TBE) virus were developed and
      evaluated. Sera from 112 patients with clinically characterized TBE virus
      infections, 27 patients with antibodies against dengue or yellow fever virus and
      100 healthy blood donors were investigated for anti-TBE virus antibodies. The
      assays yielded sensitivities of 91-95% and specificities of 91-94%. The test
      systems are valuable new tools for the diagnosis and monitoring of TBE virus
      infections.

PMID- 15146999
TI  - Significant improvement of the recombinant Borrelia IgG immunoblot for
      serodiagnosis of early neuroborreliosis.

PMID- 15146998
TI  - Immunological characterization of the complement regulator factor H-binding CRASP
      and Erp proteins of Borrelia burgdorferi.
AB  - Complement activation plays an important role in the elimination of invading
      microorganisms. Borrelia (B.) burgdorferi sensu lato the etiological agent of
      Lyme borreliosis, can resist complement-mediated killing. The mechanism of
      complement resistance of B. burgdorferi sensu stricto apparently depends on the
      expression of several outer surface proteins described as CRASPs (complement
      regulator-acquiring surface proteins). These borrelial surface proteins are able
      to bind components of the complement regulatory system, factor H and/or factor H
      like protein 1 (FHL-1), two crucial fluid-phase negative regulators of the
      alternative pathway of complement. It was previously demonstrated that one CRASP
      is encoded by a member of the erp gene family. The purpose of the study was to
      use a set of monoclonal antibodies (mAb) and polyclonal antisera to characterize
      the relatedness of factor H-binding CRASP and Erp proteins among several B.
      burgdorferi sensu stricto and B. afzelii strains. Based on the observed cross
      reactivities between B. burgdorferi sensu stricto strains LW2 and PKa-1, it is
      concluded that BbCRASP-3 is similar to ErpP, BbCRASP-4 is structurally related to
      ErpC, and BbCRASP-5 is similar to ErpA. The BaCRASP-2 and BaCRASP-4 proteins of
      B. afzelii strain EB1 reacted with both anti-ErpA and anti-ErpP antibodies
      whereas BaCRASP-5 of B. afzelii strain FEM1-D15 exclusively reacted with BbCRASP
      3/ErpP specific antibodies. Together, these data indicate that most of the factor
      H-binding CRASPs are members of the Erp protein family, which represents a
      polymorphic class of proteins with similar or identical immunological
      reactivities.

PMID- 15147000
TI  - Disappearance of specific immune response after successful therapy of chronic
      Lyme borreliosis.
AB  - 512 consecutive patients suffering from chronic Lyme borreliosis have been
      treated according to a standardized therapy regimen which was developed using the
      results of a controlled trial (Hassler et al., 1990; Hassler, 1992). Follow up
      was performed for at least 6 (maximum 16) years. In the first two years after
      initial therapy clinical and serological data were collected every six months
      including Western blot testing, later once a year.

PMID- 15147001
TI  - Borrelia burgdorferi s.l. OspA-types are widespread in Bavaria but show distinct
      local patterns.

PMID- 15147002
TI  - The zoonotic reservoir of Borrelia burgdorferisensu lato in the Mazury Lakes
      district of North-Eastern Poland.
AB  - The roles of two species of rodents: the bank vole (Clethrionomys glareolus) and
      the yellow-necked mouse (Apodemus flavicollis) in maintaining the vector Ixodes
      ricinus and Borrelia burgdorferi s.l. were studied. More particularly, seasonal
      patterns of rodent abundance and infestation rate with I. ricinus ticks as well
      as the prevalence of B. burgdorferi s.l. and the two species B. garinii and B.
      afzelii were determined. The studies were carried out in woodlands at Urwitalt
      near Mikolajki on the Mazury Lakes in 2001. A total of 196 rodents were trapped
      and 1349 I. ricinus ticks were collected. There was an increase of rodents in the
      autumn, with a maximum density of C. glareolus in October and in of A.
      flavicollis in September. The infestation rate of the investigated animals was
      above 87% and was dependent on the developmental stage of ticks and host species.
      Only two stages of I. ricinus were found on trapped rodents: larvae 80% and
      84.5%, and nymphs 7.5% and 15.5% for C. glareolus and for A. flavicollis,
      respectively. The average level of infestation with ticks on rodents appears to
      be seasonally dependent, and decreases from spring to autumn. Both methods of B.
      burgdorferi s.l. detection, PCR and IFA, showed that larvae collected from both
      species of infested rodents were infected by these spirochetes. An increase in
      the infection rates with B. burgdorferi s.l. was observed from spring to autumn
      from 12.5% to 15.6% for larval ticks collected from C. glareolus, and from 5.6%
      to 8.8% for ticks collected from A. flavicollis. The infection rates of larvae
      examined by PCR were 5% in the spring and 8% in the autumn for ticks collected
      from C. glareolus, and 10% and 5% for ticks collected from A. flavicollis. A
      total number of 329 ticks were analysed for the detection of genospecies (184 for
      B. garinii and 145 for B. afzelii). In larvae collected from C. glareolus, B.
      garinii were found in 3% and B. afzelii in 1.1% of assessed ticks. Conversely, in
      larvae collected from A. flavicollis the percentage of infected ticks was 1.5%
      for B. garinii and 1.7% for B. afzelii. The examined ear biopsies were Borrelia
      positive in 2.5% and 4.3% of the 44 bank voles and 80 yellow-necked mice,
      respectively. Both species of rodents, highly abounded in the Mazury Lakes
      district od North-Eastern Poland, may represent significant, seasonally
      dependent, zoonotic reservoirs of B. burgdorferi s.l.

PMID- 15147003
TI  - Heterogeneity of the immunodominant surface protein VlsE among the three
      genospecies of Borrelia burgdorferi pathogenic for humans.

PMID- 15147004
TI  - Serological description of Estonian patients with Lyme disease, a comparison with
      control sera from endemic and non-endemic areas.
AB  - Serological tests for Lyme disease are mostly not well standardized and cases of
      misinterpretation of test results by clinicians are rather common. The diagnostic
      value of serologic tests may also depend on the seroepidemiological situation of
      the population. The aim of the study was to compare the immunoblot pattern of
      Lyme borreliosis patients and control sera from endemic and non-endemic regions
      and to identify the most suitable interpretation criteria for our immunoblot
      test. Serum samples of 24 Estonian patients with Lyme disease, 12 sera from
      patients with tick-borne encephalitis, 40 Estonian control sera, and sera from 50
      Laplanders from North Sweden where people usually never come into contact with
      ticks were tested for IgG antibodies to Borrelia. Sonicated lysate of Borrelia
      afzelii (strain ACA1) was used in immunoblot as source of antigens. In our test
      system the following interpretation criteria gave the specificity of 96% for
      Estonian population: > or = 1 band from p58, p21, p17 and p14 plus > or = 2 bands
      from p83/100, p39, p34, p30 and p25; or > or = 4 bands from p83/100, p39, p34,
      p30 and p25. The comparison of Estonian controls with Laplanders showed that
      subclinical infections with Borrelia are rather common in Estonia. Also the rate
      of other infections, giving rise to cross-reactive antibodies, may be more
      frequent in Estonians. The frequent reactions with Borrelia antigens in a healthy
      population complicate the serodiagnosis of Lyme disease.

PMID- 15147005
TI  - Is leishmaniasis becoming endemic in Germany?

PMID- 15147006
TI  - Test systems for tick repellents.
AB  - There is an interest in the development of repellents for personal protection of
      humans and animals against ticks. Evaluation of new substances or formulations
      needs adequate test procedures to show efficacy of the compounds. A variety of
      repellent assays for ticks are described in the literature. Available biotests
      can be grouped in three categories (i) use of live hosts, (ii) use of some kind
      of tick attractant associated with hosts, or (iii) no use of attractants at all.
      The latter are often better to standardize and are cheap, but suffer from a poor
      ability to filter out weak repellents. The former two are usually more predictive
      in terms of forecasting the efficacy of the product under practical conditions,
      although sometimes difficult to standardize, particularly in the field, but
      usually expensive and time consuming. Therefore, recent developments concentrated
      on laboratory assays like the Moving-object bioassay or the human volunteer test,
      allowing the tick to display its host-seeking behaviour as close as possible to
      that shown in nature, yet offering a standardized procedure.

PMID- 15147007
TI  - Designing optically tracked instruments for image-guided surgery.
AB  - Most image-guided surgery (IGS) systems track the positions of surgical
      instruments in the physical space occupied by the patient. This task is commonly
      performed using an optical tracking system that determines the positions of
      fiducial markers such as infrared-emitting diodes or retroreflective spheres that
      are attached to the instrument. Instrument tracking error is an important
      component of the overall IGS system error. This paper is concerned with the
      effect of fiducial marker configuration (number and spatial distribution) on tip
      position tracking error. Statistically expected tip position tracking error is
      calculated by applying results from the point-based registration error theory
      developed by Fitzpatrick et al. Tracking error depends not only on the error in
      localizing the fiducials, which is the error value generally provided by
      manufacturers of optical tracking systems, but also on the number and spatial
      distribution of the tracking fiducials and the position of the instrument tip
      relative to the fiducials. The theory is extended in two ways. First, a formula
      is derived for the special case in which the fiducials and the tip are collinear.
      Second, the theory is extended for the case in which there is a composition of
      transformations, as is the situation for tracking an instrument relative to a
      coordinate reference frame (i.e., a set of fiducials attached to the patient).
      The derivation reveals that the previous theory may be applied independently to
      the two transformations; the resulting independent components of tracking error
      add in quadrature to give the overall tracking error. The theoretical results are
      verified with numerical simulations and experimental measurements. The results in
      this paper may be useful for the design of optically tracked instruments for
      image-guided surgery; this is illustrated with several examples.

PMID- 15147008
TI  - High-resolution determination of soft tissue deformations using MRI and first
      order texture correlation.
AB  - Mechanical factors such as deformation and strain are thought to play important
      roles in the maintenance, repair, and degeneration of soft tissues. Determination
      of soft tissue static deformation has traditionally only been possible at a
      tissue's surface, utilizing external markers or instrumentation. Texture
      correlation is a displacement field measurement technique which relies on unique
      image patterns within a pair of digital images to track displacement. The
      technique has recently been applied to MR images, indicating the possibility of
      high-resolution displacement and strain field determination within the mid
      substance of soft tissues. However, the utility of MR texture correlation
      analysis may vary amongst tissue types depending on their underlying structure,
      composition, and contrast mechanism, which give rise to variations in texture
      with MRI. In this study, we investigate the utility of a texture correlation
      algorithm with first-order displacement mapping terms for use with MR images, and
      suggest a novel index of image "roughness" as a way to decrease errors associated
      with the use of texture correlation for intra-tissue strain measurement with MRI.
      We find that a first-order algorithm can significantly reduce strain measurement
      error, and that an image "roughness" index correlates with displacement
      measurement error for a variety of imaging conditions and tissue types.

PMID- 15147009
TI  - Fully automatic luminal contour segmentation in intracoronary ultrasound imaging-
      a statistical approach.
AB  - In this paper, a fully automatic method for luminal contour segmentation in
      intracoronary ultrasound imaging is introduced. Its principle is based on a
      contour with a priori properties that evolves according to the statistics of the
      ultrasound texture brightness, which is generally Rayleigh distributed. The main
      interest of the technique is its fully automatic character. This is insured by an
      initial contour that is not set by the user, like in classical snake-based
      algorithms, but estimated and, thus, adapted to each image. Its estimation
      combines two pieces of information extracted from the a posteriori probability
      function of the contour position: the function maximum location (or maximum a
      posteriori estimator) and the first zero-crossing of its derivative. Then,
      starting from the initial contour, a region of interest is automatically selected
      and the process iterated until the contour evolution can be ignored. In vivo
      coronary images from 15 patients, acquired with the 20-MHz central frequency
      Jomed Invision ultrasound scanner, were segmented with the developed method.
      Automatic contours were compared to those manually drawn by two physicians in
      terms of mean absolute difference. The results demonstrate that the error between
      automatic contours and the average of manual ones is of small amplitude, and only
      very slightly higher (0.099 +/- 0.032 mm) than the interexpert error (0.097 +/-
      0.027 mm).

PMID- 15147010
TI  - Reconstruction and quantification of the carotid artery bifurcation from 3-D
      ultrasound images.
AB  - Three-dimensional (3-D) ultrasound is a relatively new technique, which is well
      suited to imaging superficial blood vessels, and potentially provides a useful,
      noninvasive method for generating anatomically realistic 3-D models of the
      peripheral vasculature. Such models are essential for accurate simulation of
      blood flow using computational fluid dynamics (CFD), but may also be used to
      quantify atherosclerotic plaque more comprehensively than routine clinical
      methods. In this paper, we present a spline-based method for reconstructing the
      normal and diseased carotid artery bifurcation from images acquired using a
      freehand 3-D ultrasound system. The vessel wall (intima-media interface) and
      lumen surfaces are represented by a geometric model defined using smoothing
      splines. Using this coupled wall-lumen model, we demonstrate how plaque may be
      analyzed automatically to provide a comprehensive set of quantitative measures of
      size and shape, including established clinical measures, such as degree of
      (diameter) stenosis. The geometric accuracy of 3-D ultrasound reconstruction is
      assessed using pulsatile phantoms of the carotid bifurcation, and we conclude by
      demonstrating the in vivo application of the algorithms outlined to 3-D
      ultrasound scans from a series of patient carotid arteries.

PMID- 15147011
TI  - Accelerated simulation of cone beam X-ray scatter projections.
AB  - Monte Carlo (MC) methods can accurately simulate scatter in X-ray imaging.
      However, when low noise scatter projections have to be simulated these MC
      simulations tend to be very time consuming. Rapid computation of scatter
      estimates is essential for several applications. The aim of the work presented in
      this paper is to speed up the estimation of noise-free scatter projections while
      maintaining their accuracy. Since X-ray scatter projections are often rather
      smooth, an approach is chosen whereby a short MC simulation is combined with a
      data fitting program that is robust to projection truncation and noise. This
      method allows us to estimate the smooth scatter projection rapidly. The speed-up
      and accuracy achieved by using the fitting algorithm were validated for the
      projection simulation of a small animal X-ray CT system. The acceleration that
      can be obtained over standard MC simulations is typically two orders of
      magnitude, depending on the accuracy required. The proposed approach may be
      useful for rapid simulation of patient and animal studies and for correction of
      the image-degrading effects of scatter in tomography.

PMID- 15147012
TI  - Emission image reconstruction for randoms-precorrected PET allowing negative
      sinogram values.
AB  - Most positron emission tomography (PET) emission scans are corrected for
      accidental coincidence (AC) events by real-time subtraction of delayed-window
      coincidences, leaving only the randoms-precorrected data available for image
      reconstruction. The real-time randoms precorrection compensates in mean for AC
      events but destroys the Poisson statistics. The exact log-likelihood for randoms
      precorrected data is inconvenient, so practical approximations are needed for
      maximum likelihood or penalized-likelihood image reconstruction. Conventional
      approximations involve setting negative sinogram values to zero, which can induce
      positive systematic biases, particularly for scans with low counts per ray. We
      propose new likelihood approximations that allow negative sinogram values without
      requiring zero-thresholding. With negative sinogram values, the log-likelihood
      functions can be nonconcave, complicating maximization; nevertheless, we develop
      monotonic algorithms for the new models by modifying the separable paraboloidal
      surrogates and the maximum-likelihood expectation-maximization (ML-EM) methods.
      These algorithms ascend to local maximizers of the objective function. Analysis
      and simulation results show that the new shifted Poisson (SP) model is nearly
      free of systematic bias yet keeps low variance. Despite its simpler
      implementation, the new SP performs comparably to the saddle-point model which
      has shown the best performance (as to systematic bias and variance) in randoms
      precorrected PET emission reconstruction.

PMID- 15147013
TI  - Improvement of depth position in 2-D/3-D registration of knee implants using
      single-plane fluoroscopy.
AB  - Two-dimensional (2-D)/three-dimensional (3-D) registration techniques using
      single-plane fluoroscopy are highly important for analyzing 3-D kinematics in
      applications such as total knee arthroplasty (TKA) implants. The accuracy of
      single-plane fluoroscopy-based techniques in the determination of translation
      perpendicular to the image plane (depth position), however, is relatively poor
      because a change in the depth position causes only small changes in the 2-D
      silhouette. Accuracies achieved in depth position using conventional 2-D/3-D
      registration techniques are insufficient for clinical applications. Therefore, we
      propose a technique for improving the accuracy of depth position determination in
      order to develop a system for analyzing knee kinematics over the full six degrees
      of freedom (6 DOF) using single-plane fluoroscopy. In preliminary experiments,
      the behaviors of errors for each free variable were quantified as evaluation
      curves by examining changes in cost function with variations in the free
      variable. The evaluation curve for depth position was more jagged, and the curve
      peak less pointy, compared to the evaluation curves of the other five variables,
      and the curve was found to behave differently. Depth position is therefore
      optimized independently of the other variables, using an approximate evaluation
      curve of depth position prepared after initial registration. Accuracy of the
      proposed technique was evaluated by computer simulation and in vitro tests, with
      validation of absolute position and orientation performed for each knee
      component. In computer simulation tests, root-mean-square error (RMSE) in depth
      position was improved from 2.6 mm (conventional) to 0.9 mm (proposed), whereas
      for in vitro tests, RMSE improved from 3.2 mm to 1.4 mm. Accuracy of the
      estimation of the remaining two translational and three rotational variables was
      found to be almost the same as that obtained by conventional techniques. Results
      of in vivo tests are also described in which the possibility of full 6 DOF
      kinematic analysis of TKA implants is shown.

PMID- 15147014
TI  - Evaluation of JPEG 2000 encoder options: human and model observer detection of
      variable signals in X-ray coronary angiograms.
AB  - Previous studies have evaluated the effect of the new still image compression
      standard JPEG 2000 using nontask based image quality metrics, i.e., peak-signal
      to-noise-ratio (PSNR) for nonmedical images. In this paper, the effect of JPEG
      2000 encoder options was investigated using the performance of human and model
      observers (nonprewhitening matched filter with an eye filter, square-window
      Hotelling, Laguerre-Gauss Hotelling and channelized Hotelling model observer) for
      clinically relevant visual tasks. Two tasks were investigated: the signal known
      exactly but variable task (SKEV) and the signal known statistically task (SKS).
      Test images consisted of real X-ray coronary angiograms with simulated filling
      defects (signals) inserted in one of the four simulated arteries. The signals
      varied in size and shape. Experimental results indicated that the dependence of
      task performance on the JPEG 2000 encoder options was similar for all model and
      human observers. Model observer performance in the more tractable and
      computationally economic SKEV task can be used to reliably estimate performance
      in the complex but clinically more realistic SKS task. JPEG 2000 encoder settings
      different from the default ones resulted in greatly improved model and human
      observer performance in the studied clinically relevant visual tasks using real
      angiography backgrounds.

PMID- 15147015
TI  - High-resolution 3-D shape integration of dentition and face measured by new laser
      scanner.
AB  - Face and dentition were measured using a high-resolution three-dimensional laser
      scanner to circumvent problems of radiation exposure and metal-streak artifacts
      associated with X-ray computed tomography. The resulting range data were
      integrated in order to visualize the dentition relative to the face. The
      acquisition interval for dentition by laser scanner was 0.18 mm, and complicated
      morphologies of the occlusal surface could be sufficiently reproduced.
      Reproduction of occlusal condition of upper and lower dentitions was conducted by
      matching the surface of the occlusal impression record with upper dentition data.
      To integrate dentition and face, a marker plate interface was devised and adopted
      on the lower dental cast or by the subject directly. Integration was performed by
      matching both sets of interface data. Reproduction of the occlusal condition and
      integration of the dentition and face were accomplished and visualized
      satisfactorily by computer graphics. The integration accuracy was examined by
      changing the attachment angle of the marker plate, and the marker plate attached
      at 45 degrees showed the smallest error of 0.2 mm. The current noninvasive method
      is applicable to clinical examination, diagnosis and explanation to the patient
      when dealing with the physical relationship between face and dentition.

PMID- 15147016
TI  - A computer-aided diagnosis for locating abnormalities in bone scintigraphy by a
      fuzzy system with a three-step minimization approach.
AB  - Bone scintigraphy is an effective method to diagnose bone diseases such as bone
      tumors. In the scintigraphic images, bone abnormalities are widely scattered on
      the whole body. Conventionally, radiologists visually check the whole-body images
      and find the distributed abnormalities based on their expertise. This manual
      process is time-consuming and it is not unusual to miss some abnormalities. In
      this paper, a computer-aided diagnosis (CAD) system is proposed to assist
      radiologists in the diagnosis of bone scintigraphy. The system will provide
      warning marks and abnormal scores on some locations of the images to direct
      radiologists' attention toward these locations. A fuzzy system called
      characteristic-point-based fuzzy inference system (CPFIS) is employed to
      implement the diagnosis system and three minimizations are used to systematically
      train the CPFIS. Asymmetry and brightness are chosen as the two inputs to the
      CPFIS according to radiologists' knowledge. The resulting CAD system is of a
      small-sized rule base such that the resulting fuzzy rules can be not only easily
      understood by radiologists, but also matched to and compared with their expert
      knowledge. The prototype CAD system was tested on 82 abnormal images and 27
      normal images. We employed free-response receiver operating characteristics
      method with the mean number of false positives (FPs) and the sensitivity as
      performance indexes to evaluate the proposed system. The sensitivity is 91.5%
      (227 of 248) and the mean number of FPs is 37.3 per image. The high sensitivity
      and moderate numbers of FP marks per image shows that the proposed method can
      provide an effective second-reader information to radiologists in the diagnosis
      of bone scintigraphy.

PMID- 15147017
TI  - The generalized spherical homeomorphism theorem for digital images.
AB  - The spherical homeomorphism conjecture, proposed by Shattuck and Leahy in 2001,
      serves as the backbone of their algorithm to correct the topology of magnetic
      resonance images of the human cerebral cortex. Using a canonical image-thickening
      technique and the authors' previously proven "spherical homeomorphism theorem for
      surfaces," we formulate and prove a spherical homeomorphism theorem which is
      valid for all digital images when utilizing the (26,6)-connectivity rule.

PMID- 15147018
TI  - Comments on: A methodology for evaluation of boundary detection algorithms on
      medical images.
AB  - In this paper we analyze a result previously published about a comparison between
      two statistical tests used for evaluation of boundary detection algorithms on
      medical images. We conclude that the statement made by Chalana and Kim (1997)
      about the performance of the percentage test has a weak theoretical foundation,
      and according to our results, is not correct. In addition, we propose a one-sided
      hypothesis test for which the acceptance region can be determined in advance, as
      opposed to the two-sided confidence intervals proposed in the original paper,
      which change according to the estimated quantity.

PMID- 15147019
TI  - Psychotherapy education: innovation and evolution.

PMID- 15147020
TI  - Implications of psychotherapy research for psychotherapy training.
AB  - This review article considers implications of psychotherapy research for
      psychotherapy training. It considers 8 themes that characterize the research
      literature. The themes involve outcome findings, common factors, empirically
      supported therapies, patient treatment matches, therapy manuals and practice
      guidelines, brief therapies, combinations of medication and psychotherapy, and
      group therapies. Each theme represents a controversial issue that has
      implications for the content of contemporary psychotherapy curricula. To assist
      trainees in becoming well-informed therapists, themes and implications such as
      these should be covered as part of their introduction to learning about the
      psychotherapies. To understand the themes and implications, as well as new
      findings that continually emerge from the research literature, trainees also need
      to be familiar with basic research methods and evaluative criteria, subjects that
      can also be covered as part of their introduction to the psychotherapies. As
      their training proceeds, research findings can be integrated with the development
      of their clinical skills in a broad range of psychotherapies.

PMID- 15147022
TI  - Integrative dimensions of psychotherapy training.
AB  - This paper investigates the influence of integrative factors on psychotherapy
      education. The broad relevance of integrative psychotherapy to residency training
      and continuing mental health education is discussed. Following a review of the
      existing literature on the education of integrative psychotherapists, the article
      systematically examines the integrative and pedagogic issues to be considered in
      planning psychotherapy training informed by integrative principles. The
      integrative issues are organized into 5 categories: attitudinal set, knowledge
      base, clinical techniques and skills, developmental tasks and challenges, and
      systemic institutional factors. The educational issues can be divided into 4
      categories: content, format and process, sequence, and faculty development. Brief
      descriptions of actual educational interventions illustrate the implementation of
      such ideas. Specific recommendations are made regarding the development of
      integrative educational initiatives and future study of unresolved questions.

PMID- 15147021
TI  - Advances in psychotherapy education.
AB  - Acquiring expertise in psychotherapy is central to the professional development
      of psychiatrists able to employ a broad therapeutic repertoire in their clinical
      practice. This article reviews how postgraduate psychiatry programs address this
      important aspect of training. We present the results of a national survey of
      psychotherapy education in Canadian psychiatry residency programs. The results
      highlight significant advances over the past decade in curriculum, in teaching
      methods, and in evaluation. These include training in evidence-based, manualized,
      time-limited therapies such as cognitive-behavioural and interpersonal therapy,
      greater attention to evaluating competence, and integrating electronic
      technology. Trends and advances in postgraduate and continuing medical
      psychotherapy education programs are considered in association with principles of
      adult learning. Health education research endorses the provision of longitudinal
      training programs that integrate learning and practice. We discuss issues related
      to the development of expertise, the importance of educational communities of
      practitioners, and the importance of attending to both educational process and
      outcomes, with a view to more effectively translating psychotherapy practice
      guidelines into sustained improvements in practice behaviours.

PMID- 15147023
TI  - Forty years of deinstitutionalization of psychiatric services in Canada: an
      empirical assessment.
AB  - OBJECTIVE: To empirically analyze the implementation of the policy of
      deinstitutionalization of psychiatric services over a 40-year period. METHOD: We
      assessed the policy of deinstitutionalization in terms of the following
      components: 1) population-based psychiatric beds, days of care in psychiatric
      hospitals (PHs); 2) days of care in psychiatric units in general hospitals (GHs);
      and 3) per capita expenditures on psychiatric services. RESULTS: There was a
      rapid closure of beds in PHs in the 1970s and 1980s, but this was associated with
      an increasing rate of days of care in psychiatric units in GHs (that is,
      transinstitutionalization). It was not until the 1990s that the overall days of
      inpatient care began to decrease. Per capita expenditures on community-based
      psychiatric services increased throughout this period. CONCLUSIONS: Standardized
      rates reveal tremendous variation among the provinces in the timing and intensity
      of deinstitutionalization.

PMID- 15147024
TI  - Comparisons between the South Oaks Gambling Screen and a DSM-IV-based interview
      in a community survey of problem gambling.
AB  - OBJECTIVE: To directly compare 2 forms of assessment for determining gambling
      problems in a community survey, and to examine the characteristics of respondents
      who endorsed DSM-IV symptoms but who scored below the formal DSM-IV diagnostic
      cut-off for pathological gambling. METHOD: We interviewed 1489 Winnipeg adults by
      phone (response rate 70.5%) using th South Oaks Gambling Screen (SOGS), a DSM-IV
      based instrument, and several gambling-related variables. RESULTS: The lifetime
      prevalence of "probable pathological gambling" (according to the SOGS, having a
      score of > or = 5) was 2.6%. The SOGS items and DSM-IV symptoms were highly
      correlated (r = 0.80), but a score of 5 or more symptoms for a DSM-IV diagnosis
      produced lower prevalence figures. Comparisons between recreational gamblers
      (those with no DSM-IV symptoms), subthreshold pathological gamblers (those with 1
      to 4 DSM-IV symptoms), and pathological gamblers (those with > or = 5 DSM-IV
      symptoms) on series of gambling-related variables (for example, high use of video
      lottery terminals) revealed that subthreshold individuals significantly differed
      from recreational gamblers and more closely approximated the characteristics
      displayed by pathological gamblers. CONCLUSIONS: SOGS items show a high degree of
      association with the DSM-IV clinical symptoms of pathological gambling, but the
      DSM-IV cut-off of 5 symptoms is more conservative in defining gambling problems.
      Results support a continuum view of gambling problems in the community. DSM-IV
      scores of 3 or 4 represent the higher end of the group officially considered
      diagnostically "subthreshold" and may be important from both a clinical and
      public health perspective.

PMID- 15147025
TI  - Spirituality and psychiatry in Canada: psychiatric practice compared with patient
      expectations.
AB  - OBJECTIVE: This study compares psychiatrists' and psychiatric patients' practice,
      attitudes, and expectations regarding spirituality and religion. METHOD: We
      mailed surveys to all Canadian psychiatrists registered with the Royal College of
      Physicians and Surgeons of Canada (n = 2890). The response rate was 42% (n =
      1204). We recruited patients from a Canadian on-line survey (n = 67) and from a
      local mental health clinic (n = 90). RESULTS: Psychiatrists had lower levels of
      beliefs and practices than did patients and the general population. In both
      groups, 47% felt there was "often or always" a place to include spirituality in
      psychiatric assessment, although the perceived importance differed. Among
      patients, 53% felt it important to have this issue addressed, and 24% considered
      the psychiatrist's spiritual interest important in their choice of psychiatrist.
      Barriers to addressing the issue of spirituality and mental health related to
      psychiatrists' concern regarding its appropriateness and patients' perception
      that interest is lacking. Psychiatrists' own beliefs and practices were strong
      predictors of spiritual inquiry. CONCLUSIONS: Although psychiatrists report lower
      levels of spiritual and religious belief than do patients, they acknowledge that
      it is important to include this topic in patient care. Increased discussion and
      education may lower reported barriers to including spirituality and religion in
      routine psychiatric assessment.

PMID- 15147027
TI  - High frequency of bipolar spectrum in outpatients with depression.

PMID- 15147026
TI  - Differences between only children and children with 1 sibling referred to a
      psychiatric clinic: a test of Richards and Goodman's findings.
AB  - OBJECTIVE: To test Richards and Goodman's hypothesis that a higher proportion of
      only children under age 5 years assessed in a psychiatric department do not
      present a psychiatric diagnosis, compared with preschool children with 1 sibling,
      and to investigate other variables relative to children in this age group with no
      psychiatric disorder, in light of Richards and Goodman's findings. METHOD: We
      gathered data from 169 children under age 5 years seen in the psychiatric
      department of a large pediatric hospital in Montreal, Quebec. RESULTS: First,
      bivariate analysis showed no differences between the proportion of only children
      and children with 1 sibling regarding absence of a psychiatric diagnosis. Second,
      multivariate logistic regression analysis revealed that child's age and mother's
      child-rearing attitudes were significant variables. Younger children (that is,
      age 0 to 2 years) and children whose mothers had "adequate" child-rearing
      attitudes (that is, not exhibiting significant impatience, rejection,
      stubbornness, neglect, or overprotectiveness) were more likely to have no
      disorder. CONCLUSION: These findings run counter to Richards and Goodman's
      results and suggest that other variables, such as child's age and mother's
      behaviour, are significant predictors of children under age 5 years having no
      diagnosis.

PMID- 15147028
TI  - Long-term lamotrigine adjunctive to antipsychotic monotherapy in schizophrenia:
      further evidence.

PMID- 15147029
TI  - Evidence for early intervention in first-episode psychosis.

PMID- 15147030
TI  - D2 antagonist augmentation in patients with a partial response to atypical
      antipsychotics.

PMID- 15147031
TI  - Achieving and sustaining remission in depression and anxiety disorders:
      introduction.

PMID- 15147033
TI  - Evidence-based strategies for achieving and sustaining full remission in
      depression: focus on metaanalyses.
AB  - The goal of therapy in the management of patients with major depressive disorder
      is to achieve and sustain remission. Extensive data on strategies to achieve
      remission have been published, and more recently, many of these data have been
      subject to systematic review and metaanalyses. This review compares data from
      metaanalyses and more recent trials on some of the therapies that may help to
      achieve remission. Strategies that have demonstrated improved rates of full
      remission in the treatment of depression include venlafaxine as initial
      antidepressant therapy, which has been shown to provide higher rates of remission
      when compared with serotonin reuptake inhibitors and tricyclic antidepressants.
      For patients who do not respond to initial medication treatment, treatments such
      as psychotherapy, exercise, light therapy, alternative medicines, and counselling
      have demonstrated benefits over placebo and may enhance remission rates when used
      in combination with antidepressants. Preventing relapse and sustaining the fully
      remitted state over the long term is also important in the management of
      depression. Continuing antidepressant therapy has been associated with excellent
      long-term outcomes for many patients. Randomized controlled clinical trials
      conducted in the last 5 years provide very good evidence to show that achieving
      and sustaining the fully remitted state is an attainable goal in the management
      of patients with depression.

PMID- 15147032
TI  - The human cost of not achieving full remission in depression.
AB  - Depression is among the most disabling and costly illnesses in the world. Despite
      good short-term efficacy outcomes in the treatment of depression, long-term
      outcomes remain disappointing. Depression continues to be missed or
      underdiagnosed and undertreated, and comorbidities are frequently not identified.
      Of particular concern is the low rate of depression treated to full remission.
      Treating only to response leaves patients with residual depressive symptoms and
      an increased risk of a recurrent or chronic course. Anything less than full
      remission should be considered a treatment failure. This article examines the
      substantial psychiatric, medical, functional, and economic costs associated with
      not achieving remission. Available pharmacoeconomic data and randomized,
      controlled clinical trials published in the last 5 years identified through
      Medline searches with terms including burden, cost, economics, serotonin reuptake
      inhibitors (also, specific agents), venlafaxine, nefazadone, mirtazapine,
      psychotherapy, remission, and depression were reviewed. One of the limiting
      factors to this review is that few trials have compared the effects of various
      antidepressant strategies on clinically relevant outcomes such as depression-free
      days and patient productivity, making the full benefit of remission more
      difficult to measure. Patients who fail to achieve a full remission have a more
      recurrent and chronic course, increased medical and psychiatric comorbidities,
      greater functional burden, and increased social and economic costs. Cost
      effective treatment for depression includes antidepressant therapies with higher
      remission rates. Antidepressants with a dual mechanism of action and combination
      therapies are associated with higher remission rates, more depression-free days,
      reduced pain-symptom morbidity, reduced health service utilization, and improved
      productivity.

PMID- 15147035
TI  - Special issues in the management of depression in older patients.
AB  - Major depressive disorder is frequently undiagnosed and untreated in older
      patients. Grief, pain, sleep issues, concurrent medications, altered physiology,
      and the presence of comorbid medical and psychiatric conditions can complicate
      the management of depression in older patients. Remission should be the goal of
      therapy in treating depression in the elderly, just as it is in younger patients,
      to maximize the impact of treatment on quality of life. Managing depression in
      older patients can be done effectively with the antidepressant therapies
      currently available, including selective serotonin reuptake inhibitors (SSRIs),
      venlafaxine, and mirtazapine. Comorbid medical conditions, which are common among
      older patients, can have a significant impact on depression and vice versa.
      Antidepressant therapy with SSRIs has demonstrated efficacy and tolerability in
      patients at high risk for cardiovascular events and stroke and in those with
      vascular dementia or Alzheimer's disease. Care should be taken to choose
      antidepressants with no or minimal effects on glucose levels in patients with
      diabetes. In addition, venlafaxine has demonstrated beneficial effects on the
      relief of the pain of diabetic neuropathy. Venlafaxine, mirtrazapine, and the
      SSRIs have demonstrated efficacy and tolerability in older patients, while
      tricyclic antidepressants have also demonstrated efficacy; however, tolerability
      can be a problem. Depression is not a natural part of the aging process, as some
      still believe. The review of current data indicates that the goal of management
      can and should be full remission. Further, the use of newer agents is safe and
      effective in this population, as long as one considers the pharmacokinetics and
      pharmacodynamic properties and inherent biological differences in the elderly
      population when selecting appropriate therapy.

PMID- 15147034
TI  - Special issues in the management of depression in women.
AB  - Depression is more prevalent in women than in men, which may be related to
      biological, hormonal, and psychosocial factors. Four depressive conditions are
      specific to women: premenstrual dysphoric disorder (PMDD), depression in
      pregnancy, postpartum depression, and depression related to perimenopause or
      menopause. Antidepressant therapy with selective serotonin reuptake inhibitors
      and venlafaxine has demonstrated efficacy in PMDD. Both continuous and
      intermittent dosing regimens were effective at usual but not at low dosages.
      Despite reluctance of some women to take medication for depression during
      pregnancy and breastfeeding, substantial evidence suggests that antidepressants
      are safe and efficacious during these periods, while untreated depression has
      negative consequences for both mother and child. In peri- or postmenopausal women
      with depression, estrogen may enhance the effects of antidepressant medications,
      although a pooled analysis of data in women aged 50 years or over treated with
      venlafaxine found that remission rates were similar in those who were taking
      estrogen and those who were not. The management of women with depression can be
      done safely and effectively using antidepressants and alternative interventions
      throughout the life cycle.

PMID- 15147036
TI  - Long-term goals in the management of acute and chronic anxiety disorders.
AB  - Many anxiety disorders are not treated to remission (symptom-free state);
      however, this should be the minimum goal of therapy. Antidepressant therapies
      have shown significant beneficial effects in the management of anxiety disorders,
      with some variability in results in specific disorders. In social anxiety
      disorder, selective serotonin reuptake inhibitors and venlafaxine extended
      release (XR) have demonstrated efficacy, with response rates varying between 40%
      and 68%. Monoamine oxidase inhibitors and cognitive-behavioural therapies are
      also effective. In patients with generalized anxiety disorder, benzodiazepines,
      paroxetine, and venlafaxine XR have demonstrated remission rates that are 15% to
      25% higher than placebo. In patients with posttraumatic stress disorder, about
      60% to 70% of patients experienced a response with antidepressant therapy,
      compared with about 40% on placebo, while remission rates in one study were 30%
      with venlafaxine, 24% with sertraline, and 20% with placebo. In patients with
      obsessive-compulsive disorder, a 25% to 35% improvement in symptom scores was
      reported in 20% to 65% of patients. In the management of panic disorder,
      paroxetine and venlafaxine XR doubled the percentage of patients who were panic
      free, compared with placebo. Ongoing antidepressant therapy further improved
      remission rates, and many patients with anxiety disorders required extended
      treatment trials before experiencing benefit. In most clinical trials, some
      benefits were seen within 3 to 4 weeks but continued to accrue throughout the 3-
      to 6-month duration of the trial. In the acute phase, patients with anxiety
      disorders should be treated aggressively with antidepressants for extended
      periods and may require long-term therapy to maintain benefits. Cognitive
      behavioural therapy is another mainstay in the treatment of all anxiety
      disorders; exposure to feared situations is necessary to move beyond phobic
      avoidance and functional impairment to full recovery, the ultimate goal of
      therapy.

PMID- 15147038
TI  - Adoptive immunotherapy of cancer using activated autologous lymphocytes--current
      status and new strategies.
AB  - After the discovery of interleukin-2 (IL-2), lymphokine-activated killer (LAK)
      cells, tumor-infiltrating lymphocytes (TILs), and cytotoxic T lymphocytes (CTLs)
      sensitized with the mixed lymphocyte-tumor culture (MLTC) system have been
      conducted in adoptive immunotherapy (AIT) trials during past 15 years. Although
      the overall response rate of tumor shrinkage was marginal (9%), locoregional
      administration of TILs for malignant effusions was effective (77%) for a decrease
      or disappearance of the effusions even in terminally-ill patients, resulting in
      an improvement of QOL. Recent advances for molecular understanding of antigen
      presentation and recognition have promoted us to enhance the efficacy of AIT by
      using cultured dendritic cells (DCs) for generating antigen-specific CTLs in
      vitro. The peptide-pulsed DC-activated killer (PDAK) cells showed tumor
      recognition against antigen-expressing cells, and were efficiently propagated
      with the IL2 plus immobilized anti-CD3 antibody (IL-2/CD3) culture system.
      Clinical trials using PDAK cells against patients with lung metastases are now
      progressed, in which peptides suitable for generating CTLs were chosen in
      individual patients using the method designated as host-oriented peptide
      evaluation (HPOE) approach. Moreover, DCs were introduced with tumor-derived RNA,
      which was amplified with the T7 promoter system, and then were used for
      stimulating lymphocytes. The tumor RNA-introduced DC-activated killer (TRiDAK)
      cells showed tumor-specific interferon-gamma spots even in a patient in whom we
      failed to generate PDAK cells using DCs and peptides, suggesting that the
      clinical trial of AIT using TRiDAK cells is warranted for the treatment of
      patients with metastatic cancer. Thus, more understanding of antigen-presentation
      and -recognition mechanisms and immune regulation systems may promote clinical
      applications of AIT to establish a novel modality of cancer treatment.

PMID- 15147037
TI  - Dendritic cell-based combined immunotherapy with autologous tumor-pulsed
      dendritic cell vaccine and activated T cells for cancer patients: rationale,
      current progress, and perspectives.
AB  - Effective adoptive cancer immunotherapy depends on an ability to generate tumor
      antigen-presenting cells and tumor-reactive effector lymphocytes and to deliver
      these effector cells to the tumor. Dendritic cells (DCs) are the most potent
      antigen-presenting cells, capable of sensitizing T cells to new and recall
      antigens. Many studies have shown that tumors express unique proteins that can be
      loaded on DCs to trigger an immune response. The current experimental and
      clinical statuses of adoptive transfer of tumor antigen-pulsed DCs and vaccine
      primed activated T cells are summarized herein. Clinical trials of antigen-pulsed
      DCs have been conducted in patients with various types of cancer, including non
      Hodgkin lymphoma, multiple myeloma, prostate cancer, renal cell carcinoma,
      malignant melanoma, colorectal cancer, and non-small cell lung cancer. These
      studies have shown that antigen-loaded DC vaccination is safe and promising for
      the treatment of cancer. In addition, tumor vaccine-primed T cells have been
      shown to induce antitumor activity in vivo. Several clinical studies are being
      conducted on the use of vaccine-primed T cells such as tumor-drainage lymph node.
      It is reasonable to consider using both tumor antigen-pulsed DCs and vaccine
      primed lymphocytes as adjuvants. We are now investigating the use of autologous
      whole tumor antigen-pulsed DCs and the DC vaccine-primed activated lymphocytes in
      patients with multiple metastasis of solid tumors.

PMID- 15147039
TI  - Immune-based novel therapies for chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a great public health problem, with an
      estimated 200 million chronically infected patients worldwide. No vaccines are
      currently available for HCV, and only a subset of HCV patients responds to
      interferon-alpha (IFN-alpha) and Ribavirin treatment. Substantial evidence has
      emerged recently to support the role of the host immune response in the outcome
      and pathogenesis of HCV infection. Our aims of this article are to present the
      immune-based novel therapeutic options for HCV infection and the evidence
      supporting their use in patients with chronic hepatitis C. There is a growing
      consensus that acute control of HCV infection is associated with a vigorous
      intrahepatic antiviral CD4+ and CD8+ T cell response. IFN-gamma was detectable in
      the livers of the chimpanzees that cleared or controlled the virus, raising the
      possibility that IFN-gamma might perform antiviral effector functions during HCV
      infection. Based on these observations, therapeutic induction of intrahepatic IFN
      gamma by adoptive immunotherapy might be able to control chronic HCV infection.
      Immune-based novel therapies appear to hold great promise in treating chronic HCV
      infection.

PMID- 15147040
TI  - Ex vivo enhancement of antigen-presenting function of dendritic cells and its
      application for DC-based immunotherapy.
AB  - Dendritic cells (DCs) are potent antigen presenting cells that are able to
      initiate and modulate immune responses and are hence exploited as cellular
      vaccines for immunotherapy. In particular DCs generated from peripheral blood
      monocytes (Mo-DCs) have been used with promising results as a new approach for
      the immunotherapy of cancer. In this study, we have analyzed the changes in the
      pattern of expression molecules on Mo-DCs during DC maturation using different
      maturation cytokine combinations and the expansion capacity of an antigen
      specific CD8+T cells monitored by flow cytometry with the fluorescent tetramers
      and anti-CD8 monoclonal antibody. These analyses revealed that the expansion of
      antigen specific CD8+T cells is the most effective when T cells were activated by
      fully maturated DCs by culturing monocytes for 5 days in the presence of GM-CSF
      and IL-4, followed by 2-3 days of maturation with pro-inflammatory mediators
      including TNFalpha, IL-6, IL-1beta and PGE2. These results pave the way to a more
      effective immunotherapy using DCs for patients with malignancy, as well as
      infectious diseases.

PMID- 15147041
TI  - Immunocytochemical study of the GH cells in the anterior pituitary gland of human
      fetus II. Anencephalic fetus.
AB  - In order to elucidate the effects of hypothalamic regulation on the morphology of
      GH cells, light and electron microscopic immunocytochemical examinations were
      carried out comparing GH cells in the anterior pituitary gland of anencephalic
      fetus with those of normal fetuses. Three types of GH cells were identified in
      the anterior pituitary gland of anencephalic fetus as well as in the normal
      fetus. Type-I is a small, round cell containing a few small secretory granules.
      Type-III is a large, polygonal cell with numerous large secretory granules. Type
      II is a polygonal cell with medium-sized secretory granules. The Type-II GH cell
      was predominant in both anencephalic and normal fetuses. The most striking
      difference between anencephalic and normal fetuses was the presence of atypical
      forms of the Type II cell. These were polygonal cells containing secretory
      granules, which were either immunopositive or immunonegative to anti-human GH
      (anti-hGH) serum. Furthermore, two other types of GH cells were identified. The
      somatomammotroph (SM cell) contained GH and PRL in different granules within the
      same cell. Also, a different type of the GH cell was noted containing two
      varieties of secretory granules; one was immunolabeled only with anti-hGH and the
      other was not immunolabeled to either anti-hGH or anti-human PRL (anti-hPRL).
      From these results, we suggest that an absence of hypothalamic regulation in the
      anencehpalic does not seriously modify GH cell morphology but induces an altered
      GH storage pattern in some of the cells.

PMID- 15147042
TI  - Effects of irradiation on cementum matrix cytokins function during periodontal
      regeneration.
AB  - The influence of gamma-ray irradiation on a cementum-impregnated gelatine
      membrane (CGM) was analyzed with emphasis on its function during periodontal
      regeneration. In brief, proteins were extracted from gamma-ray irradiated
      cementum (gammaC). With the gammaC protein, sample cells (gingival fibroblasts,
      periodontal ligament cells, and alveolar bone cells) were co-cultured, and
      cytological parameters (cell attachment, cell differentiation and alkaline
      phosphatase activity) were analyzed. Additionally, kinetics of some gene
      expression was analysed using reverse transcript RT-PCR, which included
      osteoproteogerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) mRNA. BMP-2
      and osteonectin were resistant to gamma-rays, and other cytokines involved in
      regeneration were decreased. Thus, the attachment activity of osteoblasts to
      gammaC protein was higher than that of non-irradiated cementum (control C). The
      expression of OPG/OCIF mRNA was lower in co-cultured cells with gammaC protein
      than those with in control C protein. Together the results imply that some
      cytokine in intact cementum prevents the attachment (differentiation) of bone
      cells onto the root surface, which may explain why the introduction of CGM
      following gingival flap surgery induces new cementum, new ligament and new bone
      formation, but CGM irradiated with gamma-rays for clinical use causes ankylosis.

PMID- 15147043
TI  - Establishment and characterization of a human malignant mesothelioma cell line
      (HMMME).
AB  - A cell line designated "HMMME" was established from the pleural fluids of a
      malignant mesothelioma patient. This line grew well without interruption for 12
      years and was subcultured over 200 times. The cells were spindle and roundish in
      shape and displayed a monolayer sheet in an epithelial pavement cell arrangement.
      They were neoplastic, had pleomorphic features, and easily formed multilayering
      without contact inhibition. The cell cytoplasm was strongly positive against anti
      vimentin, anti-calretinin and anti-pan-keratin, but negative against anti-BerEP4.
      The cells proliferated rapidly, and the population doubling time was about 42
      hours. Their chromosome number showed a wide distribution of aneuploidy with a
      mode in the diploid range; many marker chromosomes were observed. The cultured
      cells were easily transplanted into the subcutaneous of nude mice and produced a
      tumor classified as a malignant mesothelioma.

PMID- 15147045
TI  - Prayer in psychotherapy: an important consideration.

PMID- 15147044
TI  - Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human
      tumor cells.
AB  - The genes of the glutathione S-transferase (GST) family encode enzymes that
      appear to be critical in cellular protection against the cytotoxic effects,
      whereas p53 is a tumor suppressor gene. Despite a large number of studies on
      germline polymorphisms of GSTM1, GSTT1 and p53 genes, there have been very few
      reports on genotyping of these genes in human malignant tumor cells. In this
      study, we investigated GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety
      of human tumor cell lines originating from different organs to clarify tissue
      specific polymorphic frequency of these genes in human solid tumors. The GSTM1
      and GSTT1 genetic polymorphisms were evaluated using multiplex PCR techniques and
      PCR-RFLP analysis was conducted to identify p53 codon 72 genotypes. Gene
      expression of GSTM1 or GSTT1 was detected by RT-PCR in the cells with respective
      present genotype for each. Polymorphisms of p53 codon 72 detected by PCR-RFLP
      were also confirmed using SSCP and sequence analyses. GSTM1 and GSTT1 genotypes
      were various in 104 cell lines examined. Null GSTM1 genotype was dominant in
      small cell lung, kidney and ovarian carcinoma cells, whereas null GSTT1 genotype
      was dominant in cervical and endometrial carcinoma cells. GSTM1 and GSTT1
      genotypes in ovarian carcinoma cells were quite similar to those in small cell
      lung carcinoma cells. Polymorphic frequency of p53 codon 72 was also various
      among the cells, however, the Pro allele was found in only 1 of 6 kidney, 14
      cervical and 4 endometrial carcinoma cell lines. There was a significant
      difference in GSTM1 and p53 genotypes between 34 small cell and 24 non small cell
      lung carcinoma cells (P < 0.01). Combined study on the distribution of GSTM1,
      GSTT1 and p53 genotypes revealed that null GSTM1 genotype was associated with the
      Arg allele of p53 codon 72 in 58 lung carcinoma cells and null GSTT1 genotype was
      associated with the Pro/Pro homozygote in 104 tumor cell lines examined. This is
      the first study examining GSTM1, GSTT1 and p53 codon 72 polymorphisms in a
      variety of human solid tumor cells and suggesting that polymorphic frequency of
      these genes may be tissue- and organ-specific. The molecular interaction between
      GST gene defects and p53 codon 72 genotype in the development of human malignant
      tumors should be further investigated.

PMID- 15147046
TI  - The mind-body link enters the mainstream.

PMID- 15147047
TI  - The perspective of mystery: threading the connection between patient and nurse.

PMID- 15147048
TI  - Transference and countertransference.
AB  - TOPIC: The utility of transference and countertransference in professional
      nursing relationships. PURPOSE: To provide an introductory text for nurses new to
      these concepts. SOURCES: Literature specific to transference and
      countertransference illustrated by examples related to professional practice.
      CONCLUSIONS: Transference and countertransference influence relationships in ways
      that under certain conditions may be unhelpful to all concerned. Understanding
      how transference and countertransference manifest themselves has implications for
      the safe structuring of professional relationships.

PMID- 15147049
TI  - A self-psychology approach to narcissistic personality disorder: a nursing
      reflection.
AB  - TOPIC: The use of Heinz Kohut's self-psychology perspective in understanding and
      providing care for patients with narcissistic personality disorder (NPD).
      PURPOSE: To describe how nurses can apply the self-psychology perspective as a
      way to understand the development of self for individuals with NPD and to enhance
      the therapeutic relationship between the nurse and patient with NPD. SOURCES:
      Theoretical literature; the author's clinical experience. CONCLUSIONS: Self
      psychology provides nurses with a theoretical perspective that can enhance the
      interpersonal relationship between the nurse and patient with NPD.

PMID- 15147050
TI  - Antidepressant-induced insomnia: treatment options.

PMID- 15147052
TI  - [The free man (a model of mental health)].
AB  - The individual freedom is a basic value of mental health that must be aim of
      promotion and prevention. The human freedom is a mental unit faculty, attached to
      the reason, with a function distributed into three sequences (choice, self
      control and action). The profile of the free man is described as the author of a
      personal life organized on a vital project and a wide existential temporality,
      with a very favourable arrangement to the own well-being and other people's. The
      social liberty can only be real in a free culture.

PMID- 15147051
TI  - The case for atypical antipsychotics in bipolar disorder.
AB  - As the opening scenario illustrates about Mary and Bob, bipolar disorder can be
      devastating to individuals and families. Managing symptoms through psychotropic
      medications can help people with mental illness better manage their lives. Our
      brief review of the current research supports the effectiveness of atypical
      antipsychotic medications and, therefore, supports their use in treating bipolar
      disorder.

PMID- 15147053
TI  - [Therapeutic targets in diabetic vasculopathy].
AB  - Vascular complications are the main cause of morbidity and mortality in long-term
      diabetes mellitus. Endothelial dysfunction appears as an initial pathological
      mechanism leading to diabetic vasculopathy, which is associated with sustained
      high glucose levels and enhanced oxidative stress. Non-enzymatic protein
      glycosylation, through the formation of so-called advanced glycosylation end
      products, appears as one of the mechanisms involved in diabetes-associated
      endothelial dysfunction. Our research group further proposes that early and
      intermediate glycosylation products (Amadori products), which are able to release
      reactive oxygen species, can also play a relevant role in the development of
      diabetic vasculopathy.

PMID- 15147054
TI  - [Influence of disease on Matisse and Monet painting].
AB  - Henri Matisse (1869-1954) "Fauvisme", radically changed as for 1941, when he
      endured a severe surgery due to intestinal cancer. The resulting wound got
      necrosis, leading to a deficit at his abdominal muscles that impeached him to
      remain standing and paint. Sitting on his wheelchair, he started to cut out
      pieces of papers with which we created artistic collages. He died in 1954, aged
      84, almost 13 years after his surgery. Claude Monet (1840-1926). After a journey
      to Venice in 1908, when he was 68 years old, cataracts were detected in Monet's
      both eyes, leading to the loss of his sight on his left eye and to an abnormal
      perception of colours on his right one. These alterations can be detected at his
      pieces of work. The surgery on his right eye en 1923, evoluted to a rare
      complication, know as "Xantopsia", that is, yellow-coloured sight, which was
      partially corrected through "Zeiss" linses. He died on lung cancer on 5th
      December 1926, aged 86.

PMID- 15147055
TI  - [Gerocomia, a stage in the history of geriatrics].
AB  - It is studied the evolution of medical and social attention to aged persons in
      the historical period, and this task is known under the name of Gerocomia. They
      are analyzed the historical reasons that make it understandable and the ones
      which, in the last part of the 19th century, impose its superseding due to the
      clinical differentiation of the process of aged persons getting ill; in this way,
      a new chapter is added to the pathology which will be called Geriatrics.

PMID- 15147056
TI  - [The canine model in the gene therapy of glioblastoma].
AB  - The group of research directed by Marta Izquierdo (in which I colaborate close to
      Dra. Garcia-Escudero and other colleagues) has used in the last three years the
      linamarase/linamarin system for treatment of brain tumors in the rat. This is a
      killer/suicide method based upon the plant linamarase gene, that hydrolyses the
      innocuous substrate linamarin to acetone cyanohydrin and glucose. The acetone
      cyanohydrin spontaneously breaks down to acetone and CNH, which kills the tumor
      cell. We try this system in dogs, but we could only induce tumors large enough to
      be treated by gene therapy in 2 out of 5 adult dogs. One of those dogs was
      treated with adenovirus carrying linamarase gene, and after with linamarine,
      observing the remission of the tumor. The other, used as control, died as a
      consecuence of the tumor. The W&W canine cell line seems to behave as allogeneic
      when injected into the brain of Beagle adult dogs, and is not, therefore an
      excellent model for this type.

PMID- 15147057
TI  - [Evolution of bacterial resistance to antibiotics].
AB  - Bacterial resistance to antibiotics is often plasmid-mediated and the associated
      genes encoded by transposable elements. These elements play a central role in
      evolution by providing mechanisms for the generation of diversity and, in
      conjuntion with DNA transfer systems, for the dissemination of resistance to
      other bacteria. Resistance to antibiotics in gram-negative bacilli is most
      commonly mediated by R plasmids and by genes carried by transposons and
      integrons. In gram-positive cocci the conjugative transposons are fundamental for
      antibiotic resistance. Acquired multiple R in S. pneumoniae can result from the
      presence of transposon Tn1545, which carries determinants erm (B), tet (M),
      aph(3')-III, and catpC194.

PMID- 15147059
TI  - [Academic speech. Diego Figuera. His struggle and his work].

PMID- 15147058
TI  - [The Ebro River and the Camino de Santiago].
AB  - Humans travel for many reasons; here we concentrate in pilgrimage and the role of
      the Ebro River as their means of transportation. The Camino de Santiago through
      the Ebro is linked to the devotion to Santa Maria del Pilar de Zaragoza, where
      according to the tradition appeared in flesh and body (January 2, 40, BC). Famous
      pilgrims are Luis VII of France, Lady Blanca, daughter of Carlos III. The Ebro's
      navigability allowed sustaining the fervor alive as it is proven by the many
      records found Caton, Estrabron, Plinio, Avieno) describing its use for pilgrimage
      and commercial purposes.

PMID- 15147060
TI  - [The medical history in Spain and its problems after the new laws].
AB  - Within the last few years in spain many laws have been approved concerning health
      personnel and chiefly medical doctors. A new order has been added to the medical
      history very extensive and in great detail. The aim of those laws is to solve the
      problems related in the litigious society in connection with the first concern
      that is good patient care, with its depth, its elements, application,
      confidentiality, delimitation who can accede to it, all of it seem to be an
      improvement, but occasionally may be the original of an increase of litigation
      against the health personnel.

PMID- 15147061
TI  - [Simultaneous pancreas-kidney transplantation: evolution and future perspective].
AB  - Pancreas transplantation has become an excellent therapeutic procedure for
      Diabetes mellitus. From 1965 to 1986, 830 patients received pancreas
      transplantation in the world and these figures were reached every year during the
      90's. The characteristics of simultaneous kidney-pancreas transplantation (SPK),
      indications, operative techniques and complications are shown. The main features
      of the donors and preoperative study of the recipients to be accepted as
      candidates are referred. The experience of the Department of General and
      Digestive Surgery, and Abdominal Organ Transplantation of the Doce de Octubre
      Hospital with the first 11 SPK on end-stage diabetic renal failure is commented.
      The age range was 24 and 43 years. Eight patients had diabetic retinopathy. One
      patient died after 1 year of the transplant. Another patient had portal venous
      thrombosis and the pancreatic graft was removed. Eight patients live insulin-free
      and 1 needs moderate doses of insulin. None of the patients died as a consequence
      of the transplant though 2 of them had Mucor infection.

PMID- 15147062
TI  - [Smoking and survival in centenarians].
AB  - Cigarette smoking has been clearly linked to the most common causes of death in
      the elderly and contributes to the higher death rate and disability rate
      associated with many chronic illnesses that are common in this age group. The
      combination of smoking along with other risk factors like hypertension and
      diabetes increase high frequency disease, and disability as well as adding to an
      increase in mortality rate. In order to verify if a healthy lifestyle really
      favours longevity and how much smoking is incompatible with extreme longevity, we
      investigated the prevalence of smokers and the total smoking exposure of a sample
      of centenarians as regards residual survival and health conditions. Our sample
      consists of 157 centenarians selected among the registered residents of Rome: 39
      males and 118 females (ratio = 1:3), mean age being 101.59 years (sd = 1.8).
      83.8% of the centenarians have never smoked, 13.5% are former smokers, and 2.7%
      are active smokers. The average starting age of smoking was 21.2 years while the
      average age of quitting in former smokers was 65.7 years with an average of 44.7
      smoking years (sd = 17.1). The average number of smoked cigarettes per day is
      quite low, less than 10 cigarettes. There seemed to be a significant difference
      (p < 0.001) in gender results in smokers: male centenarians were 46%, while
      female reached only 8.1%. Statistically significant higher prevalence of diseases
      illnesses were noted among centenarian smokers over the age of 65 (p < 0.02).
      Moreover Cox's regression has shown in centenarians a lower survival rate (p <
      0.05) in smokers than in non-smokers. In conclusion, our study is evidence that
      smoking is for all, but some exceptional subjects, incompatible with successful
      aging and compromises life expectancy even in extreme longevity.

PMID- 15147063
TI  - [Artificial intelligence in medicine: project of a mobile platform in an
      intelligent environment for the care of disabled and elderly people].
AB  - A project based on the integration of new technologies and artificial
      intelligence to develop a device--e-tool--for disabled patients and elderly
      people is presented. A mobile platform in intelligent environments (skilled-care
      facilities and home-care), controlled and managed by a multi-level architecture,
      is proposed to support patients and caregivers to increase self-dependency in
      activities of daily living.

PMID- 15147064
TI  - [Viral hepatitis B among the health care workers. Experience at a health facility
      in Eastern Sicily].
AB  - AIM: to estimate the prevalence of HBV positivity considering the qualifications
      of workers exposed to biological risk in a hospital in Eastern Sicily. SUBJECTS
      AND METHOD: 1800 people exposed to biological risk: surgeons, physicians,
      laboratory workers, rehabilitation therapists, midwives, biologists and
      technicians underwent a test for HBV. RESULTS: 25 workers resulted positive to
      HBsAg, that is 1.3 % of the total population examined; the professional
      categories mostly resulting positive were the auxiliaries with a 2% prevalence,
      and professional nurses with 1.5%, followed by surgeons resulting 1% positive. In
      the positive group of HBsAg, 16 workers, equal to 64%, were also positive to the
      viral replication test. Regarding the antibody coverage, the distribution among
      workers evidenced that 30.4% of the nurses was vaccinated, against 15% of the
      surgeons and 11.7% of the physicians. 6.4% of the total population studied had a
      natural immunity, with an absolute prevalence in the auxiliary group-OTA: 9.3%,
      followed by the professional nurses with a 7.8% positivity. CONCLUSION: it is
      shown that the health care workers do not have a sufficient perception of the
      biological risk, so it is necessary to adopt new strategies to promote the
      vaccination and increase formation activities and general information.

PMID- 15147066
TI  - [Elevated concentration of serum carcinoembryonic antigen in hypothyroidism].
AB  - In this case-report we describe two patients with hypothyroidism and increased
      carcinoembryonic antigen (CEA) serum concentration. The former patient was a
      woman affected by primary autoimmune hypothyroidism, the latter by secondary
      hypothyroidism in empty sella syndrome. In both of the patients we found no
      evidence of neoplastic disease and CEA serum concentrations reverted almost
      completely to the normal range values after the patients were given the hormonal
      replacement therapy with L-thyroxine. Although the association of hypothyroidism
      with elevated CEA serum concentrations has been already reported in the
      literature, hypothyroidism is usually disregarded when a physician is facing with
      a patient with increased CEA levels. On the contrary, our data suggest that
      hypothyroidism should be taken into account in the diagnostic work-up of these
      patients, such as smoking, cholestasis, impaired liver function, chronic
      inflammatory bronchial and bowel disease.

PMID- 15147065
TI  - [Clinical criteria to diagnosing of streptococcal pharyngitis in young adult
      patients].
AB  - Most sore throat is due to viral upper respiratory tract infections, whereas the
      frequency of antibiotic use in adult patients is about 73%. We evaluate the
      clinical guidelines (approved by the CDC) about appropriate antibiotic use for
      acute pharyngitis in young adults. We observe a low prevalence (3,2%) of group A
      beta haemolytic streptococcus (GABHS) in a population of university students.
      Minimizing unnecessary antimicrobial therapy in this setting is highly desirable.
      Use of clinical criteria (Centor algorithm) does indeed identify patients whose
      risk for GABHS infection is so low that microbiological testing or antibiotic
      treatment is unnecessary.

PMID- 15147067
TI  - [A model for integrating biomedical research information].
AB  - Any new knowledge obtained from clinical research cannot easily be transferred to
      clinical practice for several reasons, including publication bias, lack of
      medical knowledge databases (or lack of their completeness), and lack of
      integration among these databases. Several initiatives have been launched to
      organize and combine scientific information and clinical knowledge in order to
      make them accessible to everyone. The most important of these initiatives was
      proposed by the National Library of Medicine, in collaboration with the National
      Institutes of Health, which has so far developed and integrated several databases
      that are currently freely available on the internet for use by researchers,
      physicians, and consumers. The more well-known of these databases are PubMed (the
      free version of Medline), ClinicalTrials.gov, National Guideline Clearinghouse,
      Drug Information and MedlinePlus. These have been designed using a uniform
      language and structure, in order to be able to organize and link the knowledge
      coming from the medical literature, clinical research, medical guidelines, and
      experience in the use of drugs. The model is restricted to the US, but could
      easily be applied in Europe and, in particular, in Italy.

PMID- 15147068
TI  - [Biochemistry of the placebo effect. Recent acquisitions].
AB  - The placebo effect is a very significant reality, both in medical practice and in
      clinical research. According to the most common opinion, placebo effect is
      essentially psychosomatic in nature. Much less well-known, however, is the fact
      that the placebo effect involves very complex biochemical events. This is
      particularly true of placebo analgesia, due to biochemical mediators produced by
      our nervous system. Approximate ideas about the placebo effect may have by no
      means negligible implications in clinical practice.

PMID- 15147069
TI  - [A new strategy for the eradication of poliomyelitis].
AB  - Today it is drastically changed the strategy to obtain the complete eradication
      of the polio disease. In fact, targeted vaccinations in the regions where the
      virus is latent are preferred to the expensive massive vaccinations of the past.
      The zones of the origin of the infection can be exactly identified by means of
      molecular biology techniques applied to the poliovirus, which is a RNA virus,
      isolated from patients or infected environments. The RNA genome of the virus is
      retrotranscribed into a double-stranded DNA molecule, colinear to its template,
      in the laboratory. This DNA is examined for its nucleotide sequence revealing
      number and types of the eventual present mutations. The comparison with the
      genome sequence of the original virus strain and with those of other strains
      isolated in previous outbursts of infection allows to precisely establish the
      geographic origin of the virus under examination. In such a way it is possible to
      set up a highly specific prophylactic vaccination that might ensure better
      results as for efficacy and reduction of the costs.

PMID- 15147070
TI  - [Anticoagulation in patients with cardiac valve prostheses].
AB  - Patients with heart valve prostheses carry a higher risk of thromboembolic events
      compared to the normal population. In many cases anticoagulation is required
      after heart valve replacement. Thromboembolic risk is related to valve prosthesis
      design, patient own characteristics and adequacy of anticoagulation. Recent
      advance in the understanding of the pathophysiology of thrombus formation and
      pharmacological characteristics of most used anticoagulants are discussed.
      Suggestions for anticoagulation regimen are given according to recent randomised
      clinical trials based on prosthesis type, site of implant and patients clinical
      characteristics. Emphasis is given for cumbersome situations such as pregnancy
      and major hemorrhage in which anticoagulation has to be interrupted.

PMID- 15147071
TI  - [The past and present history of the term "quality" in medicine].
AB  - In the medieval hospital the terms "care" and "cure" constituted a kind of
      hendiadys; in the XVIII century the quality of services was precisely identified
      for the first time, and, between the XVIII and the XIX centuries, medicine also
      began to assess the quality of professional competence, recognizing the need for
      a fair allocation of resources, and directing the health services only towards
      those who really needed them. In the XIX century the "Regolamenti" of hospital
      institutions are made compulsory in Italy, as foreseen by the Public Health Law
      of 1888. However, only during the XX century, and particularly in the second half
      of the century, quality standards are defined, together with the structuring of a
      health service and with the ever more widely felt need for a new relationship
      between the physician and the patient, and between the patient and the
      institution. In even more recent times, during the 1990s, Evidence Based Medicine
      has given a further stimulus to every currently interpreted quality systems.

PMID- 15147072
TI  - [Neurological syndromes induced by antipsychotic drugs].

PMID- 15147073
TI  - [Considerations on the correlation between psycho-physical stress and
      neurological damages].

PMID- 15147074
TI  - [A review of 445 cases of laparoscopic hysterectomy: benefits and outcome].
AB  - Hysterectomy is a major procedure indicated for women with gynaecologic
      pathologies. After reporting the first laparoscopic hysterectomy (Reich 1989),
      this technique has recently been considered as a safe and efficient alternative
      to traditional abdominal hysterectomy in the management of benign uterine
      pathologies when vaginal route is contraindicated. The laparoscopic approach
      should not be held to compete with vaginal hysterectomy. From 1995 to 2001 in our
      institute, the proportion of laparoscopic hysterectomy has increased and
      laparotomic hysterectomy has decreased. Between January 1999 and January 2001 we
      carried out 445 total laparoscopic hysterectomies. There were 5 laparotomy
      conversions for large uterus. The average haemoglobin drop was 1,36 g/dl. Median
      operative time was 95 +/- 27 min. The mean in postoperative stay was 2.7 +/- 0.8
      gg. The postoperative complications were minimal. Laparoscopic approach is less
      painful, is associated to less blood loss, shorter hospital stay, more rapid
      recovery and a better assumption by affected women. Some disadvantages are
      reported too, such as larger operating time, high rate of complication and
      experience required for performing laparoscopy including a learning curve. A
      training period is necessary to standardize the operating procedure, to put in
      place methods of avoiding complication and to reach a plateau of surgical skill.
      The purpose of this study was to show the role of total laparoscopic hysterectomy
      and how it can be performed safely with a minimal morbidity after a period of
      training in which we worked out shrewdness to get a standardized technique with
      the most effective outcome.

PMID- 15147075
TI  - [Study of the effect of medicinal product "STRESSEN" on blood levels of
      homocysteine in patients with current cardiovascular disease].
AB  - OBJECTIVE: The relationship between cardiovascular disease and high plasma levels
      of homocysteine is known; it is therefore necessary to keep the concentrations of
      this amino acid, considered an independent risk factor for these pathologies,
      within the physiological range. The objective of this study is to evaluate the
      efficacy of the medicinal product STRESSEN on homocysteinemia in patients with
      current cardiovascular disease. PATIENTS AND METHODS: The study was carried out
      on 40 patients with homocysteinemia higher than 14 micromol/l. Patients were
      divided into 2 groups of 20: one was treated with STRESSEN for 30 days and the
      other did not receive any specific therapy. Homocysteinemia was evaluated at t =
      0 and t = 30 days in both groups. RESULTS: STRESSEN determined a significative
      mean reduction of 39.2% (P < 0.0001) of plasma levels of the considered amino
      acid, which on the contrary did not change in non treated patients. CONCLUSIONS:
      The results of this study show the efficacy of STRESSEN in reducing
      homocysteinemia and, consequently, the risk of coronary disease.

PMID- 15147076
TI  - [Comparison of treatment with STRESSEN and arginine glutamate on homocysteine
      blood levels].
AB  - OBJECTIVE: Elevated plasma concentrations of homocysteine may occur because of
      impaired metabolism of this amino acid as a result of genetic factors or can be
      attributed to inadeguate blood levels of folate and vitamin B12. Recent studies
      demonstrated that STRESSEN decreases homocysteinemia more than the above
      mentioned vitamins do, as reported in literature; this behaviour could be due to
      the presence in the drug of arginine glutamate, whose specific activity, in
      comparison with STRESSEN, is here evaluated. MATERIALS AND METHODS: The trial was
      carried out on 20 patients with hyperhomocysteinemia (> 15 micromol/l) and
      affected by migraine without aura; 10 subjects have received STRESSEN and 10
      arginine glutamate. After 30 days of treatment, homocysteinemia was evaluated.
      RESULTS: Reduction of blood concentration of this amino acid was 56.3% (P <
      0.001) after STRESSEN therapy and 27.0% (P < 0.001) after arginine glutamate.
      CONCLUSIONS: Obtained results show, for the first time, the efficacy of arginine
      glutamate on homocysteinemia and strengthen the hypotesis that STRESSEN activity
      is due to all its components, including arginine glutamate that itself acts on
      this parameter.

PMID- 15147077
TI  - ["STRESSEN" in the treatment of psycho-physical stress and hyperhomocysteinemia
      in patients with migraine without aura].
AB  - OBJECTIVE: A previous clinical trial evidenced, in patients affected by migraine
      without aura, that treatment with medicinal product STRESSEN determined a
      reduction of homocysteinemia and an improved general state of health, also if the
      protocol had not provided for the latter evaluation. The aim of this study is to
      confirm, in a similar population, the efficacy of STRESSEN on
      hyperhomocysteinemia and to control the psycho-physical state of the patients by
      means of specific parameters. MATERIALS AND METHODS: 20 hyperhomocysteinemic (>
      15 micromol/ 1) patients suffering from psycho-physical stress and migraine
      without aura were enrolled. The efficacy of a 30 days treatment with STRESSEN was
      evaluated through dosage of this amino acid and through a questionnaire on the
      general state of health. RESULTS: Homocysteinemia was reduced of 52.1% (P <
      0.001) and the score representing the general state of health decreased from 1.63
      +/- 0.38 to 0.78 +/- 0.12 (P < 0.001). CONCLUSIONS: This study supported the
      effectiveness of STRESSEN treatment to restore physiological profile of
      homocysteinemia and to improve the psycho-physical conditions, usually altered by
      stress for which the drug is already indicated.

PMID- 15147078
TI  - [Tolerability of riluzole: a review of the literature].
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      with the fatal evolution. Recent studies in knowledge of the pathogenic
      mechanisms underlying ALS showed that the excitotoxicity has an important role in
      the neurodegeneration. The riluzole, an antagonist of glutamate, is the first
      drug approved by FDA for the treatment of patients with ALS. The efficacy of
      riluzole (dose recommended 50 mg twice a day) in prolonging the survival of
      patients with ALS has been demostrated in two principal controlled clinical
      trials. The most frequent adverse events related to riluzole treatment were:
      nausea, vomiting, anorexia, diarrhea, asthenia, somnolence, vertigo, circumoral
      paresthesia, abdominal pain and dizziness. Some events tend to be related to the
      dose: vertigo, diarrhea, nausea, circumoral paresthesia and anorexia appear more
      frequently with 200 mg/die that with lower dose. Generally with tree months from
      the beginning of the treatment with riluzole, an increase serum transaminase
      levels has been noted; mostly transient and regressing after two-sex months of
      treatment. A monitoring of serum transaminase levels is suggested during the
      first year of treatment with riluzole The clinical studies shows that the adverse
      events produced by riluzole are mostly reversible and dose-dependent, this
      demostrates a satifying profile of tolerability of the drug. Anyway, a deeper
      knowledge of its tolerability may lead us to a better use of riluzole, avoiding
      in this way the interruption of treatment.

PMID- 15147079
TI  - [Leptin and hypothalamus-hypophysis-thyroid axis].
AB  - The leptin system is a major regulator of food intake and metabolic rate. The
      leptin, an adipose tissue hormone whose plasma levels reflect energy stores,
      plays an important rule in the pathogenesis of such eating disorders like bulimia
      and anorexia. Thyroid hormones are major regulators of energy homeostasis. It is
      possible that leptin and thyroid hormone exert their actions on thermogenesis and
      energy metabolism via the same common effector patways. Leptin influences
      feedback regulation of the hypotalamic TRH-secreting neurons by thyroid hormone.
      Low serum levels of thyroid hormones reflect a dysfunction of the hypotalamic
      pituitary-thyroid (HPT) and hypotalamic-pituitary-adrenal (HPA) axis in patients
      with nervosa anorexia. Neuroendocrine effects of leptin include effects on the
      HPT and HPA axis. The aim of this work is to evaluated the interactions between
      leptina and HPT axis on the basis of recent published works and reviews in
      literature.

PMID- 15147080
TI  - [Advances in diagnosis and therapy of breast cancer between the 20th and the 21st
      centuries].
AB  - During the last two decades several new data have been acquired about tumor
      biology and therapy. Breast cancer is one of the more common cancers occurring,
      determining life threatening and depression in affected females. By the way a
      great interest has been developed during the time attempting to reach the
      earliest diagnosis and the more conservative treatment. However, breast cancer is
      now considered as a disease which meet the interests of several specialists
      (oncologists, surgeons, radiologists, and so), all dedicated to reduce the
      consequences of such pathology. The aim of this review is the resume of the
      progresses made in the last century about breast cancer knowledge.

PMID- 15147081
TI  - [Artificial nutrition and hydration: basic care or medical therapy].
AB  - The development of the healthcare systems has spread the use of artificial
      nutrition, both parenteral and enteral, as a solution for all the problems
      related to those diseases that prevent oral nutrition. The need for hydration and
      nutrition is a basic one for humans and its fulfilment is generally considered an
      ordinary care, always due, however the techniques of artificial nutrition raise
      the question whether they can be considered therapy that can be with holded or
      withdrawed according to criteria that avoid useless abuses (therapeutic fury).
      From an ethical point of view it is very important to define the futility (a term
      that comprises the evaluation of the proportionality, the adequacy and the
      ordinariness) of the means that medicine can offer. In the reviewed clinical
      studies the resort to artificial nutrition and hydration is justified only as a
      means of improving the quality of life, while the medical decision making on the
      usefulness or uselessness of a treatment must take into account the efficacy of
      the cure from a clinical point of view and its endurance by the patient and the
      caregiver. The adequacy and the proportionality of the cure or of the nutritional
      therapy do not depend thus on the disease or its stage, but on the clinical
      situation of the patient, on his caregivers and on the competence of the medical
      staff.

PMID- 15147082
TI  - [Nutrition and artificial hydratations: ordinary treatments or therapies].

PMID- 15147083
TI  - Physicians: the importance of studying the arts.

PMID- 15147084
TI  - Tympanic atelectasis.

PMID- 15147085
TI  - Endoscopic view of the posterior ethmoid artery.

PMID- 15147086
TI  - Hemorrhagic polyp with a contralateral contact lesion.

PMID- 15147087
TI  - Direction-fixed fluctuating positional nystagmus in a dizzy patient who had a
      drop attack.

PMID- 15147089
TI  - Glycogenic acanthosis.

PMID- 15147088
TI  - Intracerebral abscess secondary to frontal mucocele with underlying fibrous
      dysplasia.

PMID- 15147090
TI  - Organ of Chievitz.

PMID- 15147091
TI  - Proper execution of the transcolumellar incision in external rhinoplasty.

PMID- 15147092
TI  - Preventing employee theft.

PMID- 15147093
TI  - Lidocaine for the relief of incapacitating tinnitus.
AB  - Tinnitus is tolerated by most patients, but in others it is enough of a problem
      that they seek medical attention. Results of treatment have been mixed. On
      occasion, a patient is so distressed by tinnitus that he or she is incapacitated
      and seeks help in an emergency department. We describe what we believe is the
      first reported case of recurrent incapacitating tinnitus secondary to inner ear
      tertiary syphilis in which a patient successfully responded to emergency
      treatment with intravenous lidocaine.

PMID- 15147094
TI  - A new method of studying the anatomy of the posterior tympanum.
AB  - The anatomic position of the posterior tympanum compromises direct visualization
      and investigation of its structures. Therefore, assessment of its anatomy is
      limited, and surgical removal of disease in this area remains a challenge. In
      this article, the author describes a new method that can be used to fully expose,
      visualize, and measure the structures in the posterior tympanum, thereby allowing
      for further definition of the anatomy and, in turn, refinement of surgical
      techniques for the removal of disease in this portion of the middle ear. The new
      technique involves removal of the anterior canal bone and its overlying tissues
      to eliminate the mechanical barriers to the posterior tympanum, which allows for
      direct visualization and measurement of the posterior tympanic structures. This
      method has three primary advantages over other methods used to study the
      posterior tympanum. First, observations of the anatomy can be made under direct
      visualization. Second, this method permits investigators to study the anatomy and
      the relationships between structures of the posterior tympanum as they occur in
      their normal unaltered state. Third, this method allows for wide anterior access
      to the posterior tympanum, thereby making scientific research into its anatomy
      possible. Information obtained from future studies of this method can help
      further refine surgical techniques for removal of disease from the posterior
      tympanum.

PMID- 15147095
TI  - Effects of Tisseel fibrin glue on the central nervous system of nonhuman
      primates.
AB  - For many years, neurosurgeons and otolaryngologic surgeons have used the fibrin
      glue product Tisseel to repair skull-base spinal fluid leaks and to help secure
      repairs following anterior cranial-base surgery. Despite the widespread use, the
      potential focal cerebral toxicity of this fibrin glue has never been
      investigated. We studied the safety of Tisseel applied directly to neural tissue
      (brain parenchyma, cervical cord, and C3-C6 spinal roots) of 6 monkeys (Macaca
      nemestrina) to determine if any underlying biochemical injury would occur.
      Another 3 animals that served as controls received saline rather than Tisseel. We
      found that median nerve electroencephalographic tracings and somatosensory evoked
      potentials in the experimental and control animals were identical. Likewise,
      cerebrospinal fluid indicators of neuronal or brain injury, inflammatory
      responses, and infection were negative in both groups. Finally, there were no
      significant differences between the two groups with respect to edema volumes and
      apparent diffusion coefficient values. We conclude that Tisseel does not induce
      an apparent inflammatory response or abnormal neurophysiologic or histologic
      response within 5 days of its application when it is applied directly to the
      brain parenchyma or onto the cervical spinal cord.

PMID- 15147096
TI  - Extramedullary hematopoiesis occurring as a nasal polyp in a man with a
      myeloproliferative disorder.
AB  - We describe the case of a patient with a known myeloproliferative disorder who
      presented with epistaxis and what clinically appeared to be a nasal polyp. The
      mass was resected and proved to represent a focus of extramedullary
      hematopoiesis. The patient subsequently developed extramedullary hematopoiesis of
      the skin and the stomach wall. Following nasal polypectomy, he did well for a
      time, but he eventually died as a result of other complications of his disease.
      This unique case serves as a reminder that common rhinologic complaints can be a
      sign of significant and life-threatening pathology.

PMID- 15147098
TI  - Novel use of a Leyla-Yasargil retractor as an endoscope holder during endoscopic
      sinus surgery.
AB  - The authors describe a novel way of fashioning an endoscope holder from a common
      retractor and an ear speculum. Using such a device during endoscopic sinus
      surgery leaves both of the surgeon's hands free to manipulate the instruments.

PMID- 15147097
TI  - Aggressive fibromatosis of the parapharyngeal space: two cases and treatment
      recommendations.
AB  - Aggressive fibromatosis is an uncommon tumor that is locally aggressive but not
      malignant. Therefore, its classification falls between the benign and malignant
      neoplasms of soft-tissue origin. In the past, these lesions were misdiagnosed as
      low-grade fibrosarcomas. Otolaryngologists should be familiar with these lesions
      because as many as 15% of them occur in the head and neck. The treatment of
      choice is wide surgical excision, which is often difficult. Postexcision
      recurrence rates are high. Nonsurgical treatment includes radiation and
      chemotherapy, both of which are usually reserved for recurrences. We describe two
      cases of aggressive fibromatosis of the parapharyngeal space, and we review the
      available treatment options.

PMID- 15147099
TI  - Sinonasal adenoid cystic carcinoma with widespread symptomatic bony metastasis.
AB  - Adenoid cystic carcinoma is a fairly uncommon salivary neoplasm of the head and
      neck. These lesions often progress insidiously, and they have a propensity for
      early perineural spread and bony invasion. Distant metastasis to the lungs is
      fairly common and is usually fatal. We report a rare case of adenoid cystic
      carcinoma in a patient who on initial evaluation had widespread bony metastasis
      but no pulmonary involvement.

PMID- 15147100
TI  - Multiple myeloma in a patient with hoarseness, dysphagia, aspiration, and
      cervical lymphadenopathy.
AB  - Multiple myeloma, which primarily affects the elderly, is rare in the head and
      neck. We report the case of a 71-year-old man who came to us with hoarseness,
      dysphagia, intermittent aspiration, and cervical lymphadenopathy. Our work-up
      included laboratory tests, radiographic examinations, analysis of bone marrow
      aspiration, and histopathologic evaluations. Cervical lymph node biopsy confirmed
      a diagnosis of multiple myeloma. Despite treatment with chemotherapy and
      radiation, the patient died of his disease 6 months later.

PMID- 15147101
TI  - Malignant fibrous histiocytoma of the head and neck after radiation for squamous
      cell carcinoma.
AB  - A 60-year-old man presented with malignant fibrous histiocytoma of the
      oropharynx. The mass extended into the nasopharynx and larynx and caused severe
      upper airway obstruction that required emergency tracheotomy. Ten years earlier,
      he had undergone a right partial glossectomy and segmental mandibulectomy for
      squamous cell carcinoma of the right tongue base,followed by 50 Gy of radiation
      delivered over 33 sessions. The tumor was so aggressive that changes in its
      volume were visually distinguishable during physical examination over a 2-week
      hospital stay. Histologic evaluation revealed 7 mitotic figures per high-power
      field. Although radiation-induced malignant fibrous histiocytoma is rare in the
      head and neck, the recent medical literature indicates that its incidence is
      rising. This rise has been attributed to the increased effectiveness of head and
      neck cancer therapy, which results in prolonging patients' survival and, hence,
      their risk of subsequent disease. Because malignant fibrous histiocytoma is a
      late complication of radiation therapy, appearing on average 10 years following
      treatment, it is important that physicians who treat head and neck cancer monitor
      these patients over the long term and remain alert for its appearance, even
      despite the apparent "cure" of their original neoplasm.

PMID- 15147102
TI  - Cutaneous mucormycosis of the head and neck with parotid gland involvement: first
      report of a case.
AB  - Cutaneous mucormycosis is an uncommon, life-threatening, opportunistic fungal
      infection that is a distinctly different entity from the more frequent although
      still uncommon rhinocerebral form that is better known to otolaryngologists. We
      describe what to our knowledge is the only reported case of cutaneous
      mucormycosis of the face with parotid gland involvement, which occurred in a 56
      year-old man. The diagnosis was established by tissue biopsy. The patient was
      treated with antifungal medications and wide local debridement, including a total
      parotidectomy with sacrifice of the inferior division of the facial nerve. At the
      2-year follow-up, he remained free of disease. Familiarity with the risk factors
      associated with the development of cutaneous mucormycosis is critical to
      determining the need for early tissue biopsy to confirm the diagnosis. Generally
      favorable clinical outcomes are associated with prompt and aggressive medical and
      surgical therapy.

PMID- 15147103
TI  - Changes in clinically relevant metabolites with psychological stress parameters.
AB  - Psychological stress is associated with increased oxidative stress, a pro
      inflammatory state, increased rate of infection, and cardiovascular disease.
      Cardiovascular disease also is associated with increased stress, homocysteine,
      and C-reactive protein (CRP) levels. In this study, the authors measured various
      markers of psychological stress and correlated with homocysteine, CRP, salivary
      IgA, and oxidative stress. The results of the study showed that psychological
      stress is associated with pro-oxidant and pro-inflammatory states as evidenced by
      either decreased NT levels and/or increased CRP concentrations. Conversely,
      positive or low stress parameters, indicating good life skill mechanisms were
      associated with increased NT and decreased CRP--indications of a low pro-oxidant
      state. Homocysteine was associated with increased anger (anger-suppression and
      anger-experience), psychological parameters associated with cardiovascular
      disease and also mildly elevated CRP and homocysteine levels. Psychological well
      being and stress are correlated with biochemical parameters both positively and
      negatively in relation to immunity and cardiovascular disease processes. The
      cross-sectional design and correlational approach used in this study preclude any
      inferences of causality but suggest several potentially useful avenues for future
      research.

PMID- 15147104
TI  - Assessing subjective daytime sleepiness: an internal state versus behavior
      approach.
AB  - The authors' purpose in the current study was to apply P. J. Lang's (1968, 1971,
      1985) theory of multiple systems of emotional response to the study of subjective
      sleepiness. A total of 274 participants completed the Stanford Sleepiness Scale
      (SSS), the Profile of Mood States (POMS), three sleepiness-related Visual
      Analogue Scales (VAS), and the Epworth Sleepiness Scale (ESS). The authors
      completed correlations and factor analysis of the 4 sleepiness measures. The SSS,
      POMS, and VAS measures were better correlated with each other than with the ESS.
      Similarly, the SSS, POMS, and VAS measures loaded highly onto one factor, whereas
      the ESS loaded highly onto a separate factor. These results indicated that the
      ESS measured a different aspect of subjective sleepiness than the SSS, POMS, or
      VAS. According to Lang's emotional responses theory, the ESS assessed a
      behavioral component of sleepiness, and the SSS, POMS, and VAS measures assessed
      an internal state related to sleepiness.

PMID- 15147105
TI  - Social structural influences on emotional support from parents early in life and
      adult health status.
AB  - The authors' purpose in this study was to identify social structural predictors
      of receiving emotional support from parents early in life and structural factors
      responsible for variations in the associations between early parental support and
      adult health status. Data from a US representative sample of 2,786 adults aged 25
      74 years suggest that men, non-Whites, and individuals from socioeconomically
      advantaged families report having received higher levels of early parental
      support. Furthermore, these analyses suggest that although adult health status is
      predicted by early parental support in general, health status among adults is
      particularly sensitive to levels of support received from a same-sex parent
      during childhood. These findings emphasize the pervasive influence of gender in
      American society and add focus to researchers' understanding of the long-term
      health effects of early parental support.

PMID- 15147106
TI  - The sense of coherence in early pregnancy and crisis support and posttraumatic
      stress after pregnancy loss: a prospective study.
AB  - A. Antonovsky (1987) defined the sense of coherence (SOC) as the ability to
      perceive a stressor as comprehensible, manageable, and meaningful. In this
      prospective study of pregnant women, the authors tested the relationships between
      the SOC in early pregnancy and crisis support and symptom severity of
      posttraumatic stress disorder (PTSD) and depression after pregnancy loss. A total
      of 1,372 women completed questionnaires in early pregnancy, including measures
      for the SOC and depressive symptoms, and were followed for every 2 months
      thereafter until 1 month after the birth due-date. Of this group, 126 women had a
      pregnancy loss, and 118 of them completed measures for crisis support, PTSD, and
      depression about 1 month later. The results showed that a stronger SOC in early
      pregnancy renders women somewhat resilient to symptoms of PTSD and depression
      after pregnancy loss, which appears to be due to the mobilization of crisis
      support.

PMID- 15147107
TI  - The buffering effects of active coping on the relationship between SES and
      cortisol among African American young adults.
AB  - Cortisol levels have consistently been related to socioeconomic status (SES).
      Possible moderators for this relationship are coping styles that are known to
      moderate relationships between cardiovascular factors and SES. The authors
      examined whether coping style moderated a relationship between resting cortisol
      levels and various measures of SES in a sample of urban, African American young
      adults. Those scoring low on coping style had high cortisol levels if they were
      currently students or unemployed. This effect, however, differed for men and
      women. The authors suggest that coping style may play an adaptive role regarding
      salivary cortisol measures in young adults when they are students or unemployed.
      Active coping may help protect against stress among young African American
      adults.

PMID- 15147108
TI  - Atypical antipsychotics in the treatment of affective symptoms: a review.
AB  - Atypical antipsychotics have demonstrated beneficial effects on affective
      symptoms, in addition to antipsychotic activity. Consequently, their role in the
      treatment of bipolar disorder and treatment-resistant or psychotic depression has
      been explored. Adjunctive atypical antipsychotic therapy appears to benefit
      patients experiencing manic episodes of bipolar disorder, and some studies
      suggest that monotherapy may also be efficacious. Clinical studies of patients
      with schizoaffective disorder and major depression support the use of atypical
      antipsychotics to treat depression. This review focuses on risperidone,
      olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs
      demonstrate activity against manic episodes of bipolar disorder when used as
      adjunctive therapy and possibly as monotherapy and that depression in patients
      with schizoaffective disorder also responds to these agents.

PMID- 15147109
TI  - Tolerability issues during long-term treatment with antidepressants.
AB  - Depressive disorders are highly prevalent in the general population. Long-term
      treatment with antidepressants consolidates the improvement obtained during the
      acute phase of the treatment and prevents relapses and recurrences of the
      disorder. On the other hand, there is growing evidence that antidepressant side
      effects may limit patients' quality of life and social functioning, as well as
      affect patients' health and treatment adherence. Most studies concerning
      antidepressant treatment have focused on short-term tolerability, ignoring both
      early-onset persistent side effects and late-onset side effects that are reported
      during long-term treatment. Nevertheless, these long-term treatment side effects
      are likely to have a dramatic impact on patient outcome and treatment adherence.
      Common long-term side effects of antidepressants are weight gain, sexual
      dysfunction, sleep disturbances, fatigue, apathy, and cognitive impairment (e.g.,
      working memory dysfunction). Usual strategies for the management of these long
      term side effects are: changing drug daily schedule, various augmentation
      therapies, antidepressant switches, drug-holidays, and dose tapering, with the
      latter two strategies being strongly discouraged on the basis of concerns that
      patients' depressive episodes may return. Selective serotonin reuptake inhibitors
      (SSRIs) and atypical antidepressants (e.g., venlafaxine, bupropion, and
      nefazodone) show a relatively favorable short-term as well as long-term
      tolerability compared with older drugs (e.g., tricyclics and monoamine oxidase
      inhibitors). Therefore, clinicians are likely to prefer them in usual practice,
      especially among patients requiring maintenance treatment. The present review
      focuses on management of long-term side effects.

PMID- 15147110
TI  - Impulse control disorders: clinical characteristics and pharmacological
      management.
AB  - This article reviews the current knowledge of the clinical characteristics and
      pharmacological management of pathological gambling, kleptomania, and compulsive
      buying. Specifically, the article summarizes the phenomenology and associated
      psychopathology of these disorders and presents study results of the various
      pharmacological agents used to treat these disorders--serotonin reuptake
      inhibitors, opioid antagonists, mood stabilizers, and atypical antipsychotics.

PMID- 15147111
TI  - Parents with psychosis.
AB  - This study examined the prevalence of parenthood in a community-based sample of
      first-admission patients with DSM-IV diagnoses of Schizophrenia/Schizoaffective
      Disorder, Bipolar Disorder with psychotic features and Major Depressive Disorder
      with psychosis. A total of 130 (28.7%) of 453 patients were parents at the time
      of first admission. Women were twice as likely as men to be parents in all
      diagnostic groups. Patients with mood disorder with psychosis were twice as
      likely to be parents as those with Schizophrenia/Schizoaffective Disorder.
      Substance Use Disorder was a common comorbidity among fathers and to a somewhat
      lesser extent among mothers as well. At the time of admission, over three
      quarters of mothers were living with their children, as were half or more of the
      fathers with mood disorder. Most continued to live with their children after
      discharge. Almost 40% of mothers with mood disorders were living as single
      parents both before and after admission. Almost three-quarters of the children
      were under 16 years of age. Over 40% of mothers in all diagnostic categories had
      at least one child under 5 years of age. About 20% of mothers in all 3 diagnoses
      experienced the onset of psychosis within 6 months of childbirth. Over half of
      these experienced psychotic symptoms related to the child or had neglected the
      child prior to admission. Our findings contrast with earlier studies from more
      chronic patient samples in documenting that first-admission patients with
      psychosis are generally intimately involved in their children's lives both before
      and after admission. Despite the fact that over three-quarters of these parents
      were still in treatment at 6-month follow-up, there was virtually no evidence
      that any form of educational or family-oriented treatment was offered to these
      parents. These results, coupled with earlier reports of highly disrupted family
      lives and serious adverse outcomes among the children of chronically ill parents,
      underscore the need for early family intervention programs. In addition, there is
      a need for systematic research to identify effective treatment interventions for
      this population.

PMID- 15147112
TI  - Cognitive behavioral group therapy in panic disorder patients: the efficacy of
      CBGT versus drug treatment.
AB  - The aim of our study was to evaluate the effectiveness of Cognitive Behavioral
      Group Therapy (CBGT) in the treatment of Panic Disorder (PD) and to compare the
      treatment outcome of CBGT versus Paroxetine pharmacotherapy. Fifty seven patients
      referred to our anxiety disorder clinic for the treatment of PD were randomly
      allocated to receive either CBGT or Paroxetine. Follow up was done by a masked
      rater after four and twelve weeks of treatment in order to compare the efficacy
      of CBGT versus Paroxetine. CBGT and Paroxetine were both effective in the short
      term treatment of PD. Assessments at weeks four and twelve of treatment showed no
      statistically significant differences between the two groups in terms of
      treatment outcome. Treatment with CBGT alone for the acute phase of PD appears to
      be equally efficacious to treatment with Paroxetine alone. Our study shows that
      CBGT produced beneficial results, for it was associated with a reduction in the
      number and frequency of panic attacks and with an improved feeling of well-being.

PMID- 15147113
TI  - Anxiety and impaired social function in the elderly.
AB  - The effect of anxiety on impairment in activities of daily living was examined
      among elderly individuals residing in a long-term care setting. Eighty one
      subjects received complete assessments of psychiatric symptoms, cognitive
      impairment, and ability to perform daily living tasks. A multivariate analysis
      was conducted to determine the relative influence of anxiety, cognitive status,
      and depressive symptoms on daily living skills. The presence of anxiety was
      significantly associated with reduced functional status in performing activities
      of daily living. This relationship remained significant even after controlling
      for the presence of concurrent depressive symptoms as well as cognitive
      impairment. Anxiety is a significant source of morbidity among elderly
      individuals and substantially impairs social function over and above the effects
      of depression and cognitive decline. Current interventions for anxiety such as
      benzodiazepines may have adverse cognitive effects, hence more specific
      intervention strategies for anxiety may be very important for this population.

PMID- 15147114
TI  - Nutritional transition in the backdrop of early life origin of adult diseases: a
      challenge for the future.

PMID- 15147115
TI  - The toxicological quandary in the use of plasticizers in medical devices.

PMID- 15147116
TI  - HCV genotyping in India--quo vadis?

PMID- 15147117
TI  - Dendritic cell, the immunotherapeutic cell for cancer.
AB  - Dendritic cells play an important role in the development of effective cancer
      vaccines. These cells have the potential to present tumour-specific antigens and
      thereby induce an immune response. Various studies involving clinical trials have
      investigated the efficacy of administering antigen-loaded dendritic cells for
      cancer therapy. In order to design such experiments it is important to consider
      specific antigens, which initiate either a CD4+ or CD8+ response or both. The
      present review discusses the unique properties of dendritic cells as an
      immunotherapeutic cell for cancer.

PMID- 15147119
TI  - Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C
      infection in India.
AB  - BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV), an important cause of chronic
      hepatitis, cirrhosis and hepatocellular carcinoma, shows a considerable genetic
      heterogeneity among hepatitis C virus isolates from all over the world. At least
      six main groups of sequence variants are recognized. The natural history of
      disease and response to treatment may be related to the genotype of HCV in a
      particular patient. Antigenic differences between genotypes also have
      implications for optimal design of serological sequencing and confirmatory assays
      for HCV. The present study was undertaken with the objective to find out various
      genotypes of hepatitis C virus prevalent in Indian patients with chronic
      hepatitis C infection. METHODS: Thirty six consecutive newly diagnosed patients
      with chronic hepatitis C infection were included in the study. HCV RNA was
      extracted from the serum by standard guanidinium thiocyanate method. Following
      reverse transcription and amplification, the HCV genotypes were determined by
      line probe assay (INNO-LiPA HCV II). RESULTS: Of the 36 patients, genotype 3 was
      found in 24 (66.6%). Of these 24 patients, 3a was seen in 5 patients (13.8%), 3b
      in two (5.5%) and mixed subtype 3a and 3b in 17 patients (47.2%). Genotype 1 was
      found in 5 patients (13.8%), with 1b in 1 and 1a in rest four cases. Two patients
      (5.5%) were infected with genotype 2 (subtype 2a and mixed subtype 2a, 2b
      respectively). One (2.7%) was infected with genotype 4 (4a). Mixed genotype
      infection was found in 4 patients (11.1%). INTERPRETATION & CONCLUSION: The
      present findings showed that genotype 3 of hepatitis C virus was the most
      prevalent genotype in patients with chronic hepatitis C in this part of India.

PMID- 15147118
TI  - Changes in some hormones by low doses of di (2-ethyl hexyl) phthalate (DEHP), a
      commonly used plasticizer in PVC blood storage bags & medical tubing.
AB  - BACKGROUND & OBJECTIVES: Di (2-ethyl hexyl) phthalate (DEHP), a plasticizer
      commonly used in PVC blood storage bags leaches out in significant amounts into
      blood during storage. In view of many reports on the toxicity of this compound,
      it was considered necessary to investigate the effect of DEHP at the low level
      solubilized in blood on some important hormones in rats and in human blood stored
      in DEHP plasticized blood bags. METHODS: Rats were administered DEHP at a low
      level of 750 microg/100 g body weight on alternate days for 14 days. Changes in
      the serum insulin, blood glucose, liver glycogen level and T3, T4 and thyroid
      stimulating hormone (TSH) as well as cortisol in the serum were studied. Changes
      in the hormones were also studied in blood stored in DEHP plasticized PVC bags.
      RESULTS: The results indicated decrease in serum insulin, cortisol and liver
      glycogen, and increase in blood glucose, serum T3 and T4 in rats receiving DEHP.
      These changes were reversed when administration of DEHP was stopped. Similar
      changes in hormones were also observed in the blood stored in DEHP plasticized
      blood bags. INTERPRETATION & CONCLUSION: The results indicated that
      administration of DEHP at low levels to rats caused symptoms of diabetes, thyroid
      and adrenocortical dysfunction. Though the results obtained in rats cannnot be
      extrapolated to human, the fact that similar hormonal changes seen in human blood
      stored in DEHP plasticized blood bags may suggest possibility of DEHP causing
      similar changes in human. The fact that these changes were reversed in rats when
      DEHP administration was stopped, indicates that transfusion of a few units of
      blood to a recipient may not be harmful, but it may pose a problem during
      repeated transfusions such as in thalassaemia patients.

PMID- 15147120
TI  - Molecular characterization of echovirus 11 isolates from India.
AB  - BACKGROUND & OBJECTIVES: Echovirus 11 (ECV11) is one of the most frequent non
      polio enteroviruses isolated from stool samples of children with acute flaccid
      paralysis in north India. The present work was undertaken to study the sequence
      variability in the 440 bp of 5'-non-translated region of ECV11 genome using
      heteroduplex mobility assay (HMA). METHODS: Twelve ECV11 isolates were studied
      for sequence variability in the 5'-non-translated region (5'NTR) using the HMA
      followed by nucleotide sequencing. HMA was used to determine sequence diversity
      between Indian ECV11 isolates and prototype Gregory strain. HMA results were
      confirmed by 5'NTR nucleotide sequencing of five Indian ECV11 isolates. RESULTS:
      HMA results showed high genomic diversity between the prototype Gregory strain
      and Indian ECV11 isolates. All isolates were grouped into five different types of
      heteroduplex mobility patterns with respect to Gregory strain. A 440 bp 5'NTR
      fragment of five ECV11 isolates representing different heteroduplex patterns, was
      sequenced. The sequence alignment showed that 5'NTR of Indian isolates was
      different from prototype Gregory strain and identical to the ECV11 isolates of
      Finland and Hungary. Phylogenetic analysis including ECV11 isolate sequences from
      different parts of the world showed that Indian ECV11 isolates represented a
      different subgroup. INTERPRETATION & CONCLUSION: The results of the present study
      suggested that the HMA could be successfully used as a preliminary screening
      method for sequence variability determination of enterovirus field isolates. The
      sequence data generated on ECV11 isolates from India will be useful for future
      studies of endemic genotypes of echovirus.

PMID- 15147121
TI  - Contact of Entamoeba histolytica with baby hamster kidney-21 (BHK-21) cell line
      on cysteine proteinase activity.
AB  - BACKGROUND & OBJECTIVES: Entamoeba histolytica, the causative agent of amoebiasis
      and amoebic liver abscess, lyses host cells by direct contact using surface
      lectins and releases cysteine proteinase (CP). Virulence of E. histolytica is
      directly related to activity of its CP. The relationship of CP activity and
      cytotoxicity has not been established. The present study was carried out to
      explore the events following contact of E. histolytica with target cells.
      METHODS: Protease activity of E. histolytica was measured by azocaseine and
      haemoglobin assays, and cysteine proteinase activity was assessed by substrate
      gel electrophoresis. Target cell lysis was measured by chromium release assay.
      RESULTS: Protease activity of E. histolytica was increased 2.5-fold following
      contact with BHK-21 cell line. CP activity of trophozoites alone was visualized
      at position 56, 35 and 29 kDa in substrate gel electrophoresis. Contact of
      trophozoites with target cells augmented the cytotoxic activity of amoebic CP.
      The increase in CP activity seen by substrate gel electrophoresis and
      cytotoxicity assay was blocked by pretreatment with E 64, a specific CP inhibitor
      and GalNAc, a contact inhibitor. INTERPRETATION & CONCLUSION: The present data
      showed the involvement of amoebic CP in cytotoxicity and that the CP activity was
      enhanced on lectin-mediated contact of E. histolytica to the target cells.
      Further studies need to be done to understand the mechanism at the molecular
      level.

PMID- 15147122
TI  - Granulocyte macrophage colony stimulating factor augmented hepatitis B vaccine
      protocol for rapid seroprotection in voluntary kidney donors.
AB  - BACKGROUND & OBJECTIVES: Conventional hepatitis B vaccine protocols do not
      provide rapid seroprotection against hepatitis B. This randomized controlled
      trial was carried out to investigate the efficacy of granulocyte macrophage
      colony stimulating factor (GM-CSF) augmented double-dose vaccine protocol in
      voluntary kidney donors prior to donor nephrectomy. METHODS: A total of 54 kidney
      donors, who had no history of hepatitis B infection, hepatitis B vaccination and
      tested negative for anti-HBs and anti-HBc antibodies were randomly allocated to
      the control or test groups. GM-CSF (300 microg) was administered subcutaneously
      on day 0, followed by 40 microg of recombinant hepatitis B vaccine
      intramuscularly on the same deltoid on day 1. The control group received only 40
      microg of intramuscular hepatitis B vaccine. Anti-HBs titres were measured at the
      end of 4 wk. RESULTS: Of the 54 donors studied, there was a significant (P<0.003)
      seroconversion in the GM-CSF group (82%) compared to the control group (37%),
      after a single immunization with double-dose recombinant hepatitis B vaccine by 4
      wk. Minor side effects such as fever in four patients and myalgia in three were
      noticed. INTERPRETATION & CONCLUSION: GM-CSF augmented double-dose hepatitis B
      vaccine could be used in unvaccinated patients when a rapid response is desired.

PMID- 15147123
TI  - Cushing's syndromes, insulin resistance and endocrinopathic laminitis.

PMID- 15147124
TI  - The pathogenesis of acute laminitis: fitting more pieces into the puzzle.

PMID- 15147125
TI  - Evidence for vascular and enzymatic events in the pathophysiology of acute
      laminitis: which pathway is responsible for initiation of this process in horses?
AB  - To date, there is a substantial amount of data to support the hypotheses that
      vascular and enzymatic changes are ongoing in experimental laminitis.
      Furthermore, there is substantial in vitro evidence that the enzymatic changes
      weaken the dermo-epidermal attachments leading to mechanical failure of the hoof
      bone interface of the equine digit. However, investigators of both the vascular
      and enzymatic theories have, to date, been unable to substantiate the effects of
      these pathophysiological changes in vivo on laminar tissues of horses afflicted
      with experimentally induced or naturally acquired laminitis. In addition, the
      effects of laminitis-inducing treatment have not been prevented or reversed by
      treatment with an MMP inhibitor or a vasoactive antagonist. It is possible that
      there is simultaneous activation of the vascular and enzymatic pathways and/or
      other inflammatory processes. Moreover, the third theory involving mechanical
      factors cannot be discounted simply because strong evidence for vascular and
      enzymatic changes exists. It is common for horses with severe musculoskeletal
      disease affecting weightbearing on a limb to develop laminitis in the
      contralateral limb. It remains to be determined what factors are responsible for
      initiation of laminitis in these individuals. Evidence has not been presented
      that precludes the possibility of coincident occurrence of vascular and enzymatic
      changes. In fact, many of the inflammatory mediators (e.g. interleukin-1beta)
      found in laminitic tissues can concurrently stimulate synthesis of vasoactive
      substances and activate MMPs. Because enzymatic action on proteins is largely
      dependent on the concentrations of proteins and enzyme, the enzymatic theory is
      not dependent upon increased delivery of enzymes via increased capillary flow.
      Likewise, because vascular changes can alter tissue function via increased
      capillary flow and oedema formation, the vascular theory is not dependent upon
      decreased capillary flow. It is true that naturally acquired laminitis is widely
      variable in severity and predisposing diseases. Therefore, most probably there
      are multiple mechanisms involved in the initiation and propagation of the
      pathophysiologic cascade(s) and, therefore, successful intervention will
      necessitate multiple treatment modalities.

PMID- 15147126
TI  - Hoof wall wound repair.
AB  - REASONS FOR PERFORMING STUDY: Surgical stripping of the hoof wall results in a
      wound that heals remarkabley well. In contrast, lamellae recovering from
      laminitis are often deformed. Investigating lamellar wound healing may aid
      understanding of laminitis. OBJECTIVES: To document temporal changes in the
      lamellar basement membrane (BM), dermis and epidermis after surgery. METHODS:
      Wall strips were made in the dorsal hoof wall midline of 6 mature horses.
      Immunohistochemistry was used to document changes in the basement membrane (BM)
      and detect proliferation of epidermal cells in lamellar tissues harvested at
      intervals. A conforming metal plate was screwed to the hoof wall to maintain
      alignment of the wound edges. RESULTS: Wall stripping caused lamellar tips to
      snap and remain behind in the dermis along with the majority of the lamellar BM
      and some lamellar basal cells. Three days later the BM was intact and new
      lamellae had been reconstructed by proliferation of surviving epidermal cells. By
      5 days the surface of the stripped zone was covered with yellow epidermis that
      subsequently thickened and hardened. Eventually the hoof wall deficit was
      replaced by new wall growing down from the coronet. The conforming metal plate
      and post operative analgesic ensured minimal lameness. CONCLUSIONS AND POTENTIAL
      RELEVANCE: In wall stripped lamellae the BM survives virtually intact and is used
      as a template for proliferating cells, from snapped-off lamellar tips, to migrate
      and quickly achieve repair to near normality. In laminitis epidermal dysadhesion
      and lamellar BM destruction occurs and lack of a functional BM template may
      explain the prolonged and abnormal repair of affected lamellae.

PMID- 15147127
TI  - Prolonged, continuous distal limb cryotherapy in the horse.
AB  - REASONS FOR PERFORMING STUDY: The recommended duration of cryotherapy in horses
      is currently extrapolated from human medicine. Prolonged, continuous cryotherapy
      (days rather than minutes) may be of therapeutic value if it is safe and well
      tolerated. OBJECTIVES: To evaluate the effect of prolonged, continuous
      application of ice and water to the equine distal limb. METHODS: A slurry of ice
      and water was applied to the right forelimb of 4 Standardbred horses for 48 h.
      Hoof temperature, ambient temperature and ice boot temperature were logged
      continuously and clinical observations recorded every 2 h. Lameness examinations
      were performed prior to application and 1 week, 6 months and 1 year after removal
      of the ice boot. RESULTS: Continuous cryotherapy was well tolerated and resulted
      in marked cooling of the treated foot. No significant variation in clinical
      parameters was noted, and no lameness or gross pathology noted in the treated
      limbs at any examination period. CONCLUSIONS: The continuous application of ice
      and water is a safe and effective means of cooling the equine distal limb. The
      extremely low, constant temperatures achieved may be of benefit in the management
      of various distal limb conditions. POTENTIAL RELEVANCE: Providing clinicians and
      research workers with a potent therapeutic/prophylactic modality for disorders of
      the equine distal limb.

PMID- 15147128
TI  - Equine laminitis: increased transcription of matrix metalloproteinase-2 (MMP-2)
      occurs during the developmental phase.
AB  - REASONS FOR PERFORMING STUDY: The dysadhesion and destruction of lamellar
      basement membrane of laminitis may be due to increased lamellar metalloproteinase
      activity. Characterising lamellar metalloproteinase-2 (MMP-2) and locating it in
      lamellar tissues may help determine if laminitis pathology is associated with
      increased MMP-2 transcription. OBJECTIVES: To clone and sequence the cDNA
      encoding lamellar MMP-2, develop antibody and in situ hybridisation probes to
      locate lamellar MMP-2 and quantitate MMP-2 transcription in normal and laminitis
      tissue. METHODS: Total RNA was isolated, fragmented by RT-PCR, cloned into vector
      and sequenced. Rabbit anti-equine MMP-2 and labelled MMP-2 riboprobe were
      developed to analyse and quantitate MMP-2 expression. RESULTS: Western
      immunoblotting with anti-MMP-2 detected 72 kDa MMP-2 in hoof tissue homogenates
      and cross-reacted with human MMP-2. Immunohistochemistry and in situ
      hybridisation detected MMP-2 in the cytoplasm of basal and parabasal cells in
      close proximity to the lamellar basement membrane. Northern analysis and
      quantitative real-time PCR showed MMP-2 expression significantly (P < 0.01)
      elevated in laminitis affected tissues. CONCLUSION: The lamellar pathology of
      laminitis is associated with increased transcription of MMP-2. POTENTIAL
      RELEVANCE: Real-time PCR analysis of lamellar MMP-2 accurately monitors laminitis
      development at the molecular level and can be used diagnostically and for testing
      preventive strategies. Controlling increased MMP-2 transcription may ameliorate
      or prevent laminitis in high risk clinical situations. Our findings represent a
      warning to clinicians that the basement membrane lesion of laminitis is insidious
      and well under way before clinical signs are apparent.

PMID- 15147129
TI  - Biochemical indices of vascular function, glucose metabolism and oxidative stress
      in horses with equine Cushing's disease.
AB  - REASONS FOR PERFORMING STUDY: The mechanisms underlying the increased risk of
      laminitis in horses with equine Cushing's disease (ECD) are poorly understood.
      HYPOTHESIS: That abnormalities in glucose homeostasis, similar to those which
      cause microvascular dysfunction in human diabetics, contribute to development of
      laminitis in horses with ECD. METHODS: Thirty-one aged horses were divided into 3
      groups based on clinical signs and dexamethasone suppression testing (DST). Group
      1 (n = 12) had clinical ECD as evidenced by hirsutism. Group 2 (n = 10) had a
      positive DST but no hirsutism. Group 3 (n = 9) were controls without ECD, with a
      negative DST and no clinical evidence of ECD. Biochemical indices of glucose
      metabolism, vascular function and oxidative stress were determined in single
      morning blood samples. RESULTS: Group 1 had abnormalities in glucose homeostasis,
      including increased levels of glucose and insulin, compared to Groups 2 and 3.
      Groups 1 and 2 had significantly lower plasma thiol (PSH) levels and
      nonsignificantly lower albumin-corrected PSH levels than Group 3, consistent with
      oxidative stress. CONCLUSIONS AND POTENTIAL RELEVANCE: The observed abnormalities
      in glucose metabolism and oxidative stress could potentially contribute to
      development of laminitis in horses with ECD, by similar mechanisms to those that
      cause microvascular dysfunction in human diabetics. The absence of inter-group
      differences in the biochemical indices of vascular function precludes their use
      as preclinical diagnostic indicators of vascular dysfunction. The study also
      highlighted limitations in the premortem diagnosis of ECD.

PMID- 15147130
TI  - Equine laminitis: loss of hemidesmosomes in hoof secondary epidermal lamellae
      correlates to dose in an oligofructose induction model: an ultrastructural study.
AB  - REASONS FOR PERFORMING STUDY: Light microscopical studies show that the key
      lesion of laminitis is separation at the hoof lamellar dermal-epidermal
      interface. More precise knowledge of the damage occurring in the lamellar
      basement membrane zone may result if laminitis affected tissue is examined with
      the transmission electron microscope. This could lead to better understanding of
      the pathogenesis of lesions and the means of treatment or prevention. OBJECTIVES:
      To investigate the ultrastructure of acute laminitis as disease of greater
      severity is induced by increasing oligofructose (OF) dosage. METHODS: Three pairs
      of normal horses, dosed with OF at 7.5, 10 and 12.5 g/kg bwt via nasogastric
      intubation, developed laminitis 48 h later. Following euthanasia, their forefeet
      were processed for transmission electron microscopy. Lamellar basal cell
      hemidesmosome (HD) numbers and the distance between the basal cell plasmalemma
      and the lamina densa of the basement membrane were estimated and compared to
      control tissue. RESULTS: Increasing OF dosage caused greater HD loss and more
      severe laminitis. The characteristic separation of the basement membrane,
      cytoskeleton failure and rounded basal cell nuclei results from combined HD
      dysassembly and anchoring filament failure. CONCLUSIONS: Without properly
      assembled HDs, dysadhesion between the lamina densa of the basement membrane (BM)
      and epidermal basal cells occurs, emphasising the fundamental importance of HDs
      in maintaining attachment at the lamellar interface. Medical conditions that
      trigger lamellar matrix metalloproteinase (MMP) activation and/or compromise
      entry of glucose into lamellar basal cells appear to promote loss and failure of
      HDs and, therefore, laminitis development. POTENTIAL RELEVANCE: A correlation
      between lameness severity and escalating loss of lamellar HDs now exists. Therapy
      aimed at protecting the lamellar environment from haematogenous delivery of MMP
      activators or from glucose deprivation may control laminitis development.

PMID- 15147131
TI  - Epidermal cell proliferation in the equine hoof wall.
AB  - REASONS FOR PERFORMING STUDY: Current theories explaining how the hoof wall
      'grows' and moves past the stationary distal phalanx are speculative and based on
      incomplete evidence. Movement in the lamellar region could occur by cell
      proliferation or an enzyme-based remodelling process. Since laminitis
      pathogenesis appears to involve increased transcription and activation of enzymes
      normally involved in tissue remodelling, it is important to know precisely which
      process dominates the lamellar region of the hoof.. OBJECTIVES: To investigate
      epidermal cell proliferation in the equine hoof wall and calculate a
      proliferative index (PI) for the coronet, lamellae and toe. METHODS: An analogue
      of thymidine, 5-bromo-2'-deoxyuridine (BRdU), was infused i.v. into 5 ponies.
      After tissue harvesting, BRdU (and therefore basal cell proliferation) was
      detected immunohistochemically using mouse anti-BRdU. PIs were calculated for the
      coronet and 10 levels of the dorsal hoof wall lamellae. RESULTS: The highest PIs
      (mean +/- s.e.) were in the coronet; 12.04% +/- 1.59 and proximal lamellae (7.13%
      +/- 1.92) and are therefore growth zones of the proximal hoof wall. PIs of more
      distal lamellae were 0.11% +/- 0.04 to 0.97% +/- 0.29; significantly lower (P =
      0.05) than the lamellar growth zone. CONCLUSIONS: A 20-fold PI decrease between
      proximal and more distal lamellae suggests that the majority of the normal
      lamellae are nonproliferative and their main function is to suspend the distal
      phalanx within the hoof capsule. Remodelling within the hoof wall epidermal
      lamellae, which must occur as the hoof wall moves past the stationary distal
      phalanx, is a process not requiring epidermal cell proliferation. POTENTIAL
      RELEVANCE: A hoof lamellar epidermis that remodels using the same MMPs involved
      in laminitis pathogenesis implies that laminitis is a normal process out of
      control. Understanding MMP control and how the normal lamellar epidermis achieves
      this will help in the development of better laminitis preventative and treatment
      strategies.

PMID- 15147132
TI  - Equine laminitis: cleavage of laminin 5 associated with basement membrane
      dysadhesion.
AB  - REASONS FOR PERFORMING STUDY: The key lesion of laminitis is separation at the
      hoof lamellar dermal-epidermal interface. For this to happen the structural and
      adhesion proteins of the basement membrane zone must be altered. Which proteins
      and how damage to them leads to the lamellar separation of laminitis is unknown.
      OBJECTIVES: To investigate lamellar hemidesmosome and cytoskeleton damage and
      basement membrane dysadhesion using light microscopy (LM) and immunofluorescence
      microscopy (IFM). METHODS: Cryostat sections of lamellar tissues from 2 control
      and 6 Standardbred horses with oligofructose induced laminitis were studied using
      LM and IFM. Plectin, integrin alpha6 and BP230 antibody was used to label
      hemidesmosome intracellular plaque proteins and anti-BP180 and anti-laminin 5
      (L5) was used to label anchoring filament (AF) proteins. Cytoskeleton
      intermediate filaments were labelled using anti-cytokeratin 14. The primary
      antibodies of selected sections were double labelled to show protein co
      localisation. RESULTS: Laminitis caused reduction of transmembrane integrin
      alpha6, the AF proteins BP180 and L5, and failure of co-localisation of BP180 and
      L5. Proteins of the inner hemidesmosomal plaque, plectin and BP230, were
      unaffected. CONCLUSIONS: Loss of co-localisation of L5 and BP180 suggests that,
      during the acute phase of laminitis, L5 is cleaved and therefore, the AFs
      connecting the epidermis to the dermis, fail. Without a full complement of AFs
      separation at the lamellar dermo-epidermal junction occurs. POTENTIAL RELEVANCE:
      Suppressing or inhibiting metalloproteinase activity may prevent L5 cleavage and
      therefore the lamellar dermo-epidermal separation of laminitis.

PMID- 15147134
TI  - Equine laminitis: cryotherapy reduces the severity of the acute lesion.
AB  - REASONS FOR PERFORMING STUDY: The hypometabolic and vasoconstrictive effects of
      cryotherapy could prevent the development of laminitis. OBJECTIVES: To use distal
      limb cryotherapy to prevent laminitis induced by alimentary carbohydrate
      overload. METHODS: Laminitis was induced in 6 Standardbred horses that had one
      front limb continuously cooled in an ice/water mixture. Lameness evaluation,
      blinded lamellar histological grading and analysis for lamellar matrix
      metalloproteinase-2 (MMP-2) mRNA expression were used to evaluate the severity of
      laminitis. RESULTS: Cryotherapy was well tolerated and effective in cooling the
      feet. In each horse no lameness was observed in the treated limbs. Laminitis
      histology scores in the treated limbs were significantly less than those of the
      corresponding untreated forelimbs (P < 0.05). Laminitis histology scores in the
      treated limbs were also significantly less than those of the untreated limbs
      (fore- and hind) as a group (P < 0.05). Expression of MMP-2 mRNA in the iced feet
      was significantly (P < 0.05) less than that detected in the untreated feet.
      CONCLUSIONS: Cryotherapy, when applied to one foot, markedly reduced the severity
      of acute laminitis in this study. We propose that vasoconstriction (preventing
      delivery of haematogenous trigger factors) and hypometabolism (reduction in
      lamellar MMP activity) were the primary therapeutic mechanisms. POTENTIAL
      RELEVANCE: Although further research is needed, we suggest cryotherapy as a
      potentially effective prophylactic strategy in horses at risk of developing acute
      laminitis.

PMID- 15147133
TI  - Chronic equine laminitis is characterised by loss of GLUT1, GLUT4 and ENaC
      positive laminar keratinocytes.
AB  - REASONS FOR PERFORMING STUDY: Equine laminitis is a multifactorial connective
      tissue disorder with major implications for the welfare of horses. There are few
      published studies on phenotypic markers for identification of equine laminar
      keratinocytes using immunohistochemical techniques. OBJECTIVES: To establish
      whether the epithelial sodium channel (ENaC) and the GLUT1 and GLUT4 facilitative
      glucose transporters may be used as phenotypic markers for identification of
      equine laminar keratinocytes using immunohistochemical techniques to monitor
      changes in the keratinocyte population in laminitis. METHODS: Histology and
      immunohistochemistry using polyclonal antibodies to the alpha subunit of ENaC
      (alphaENaC), GLUT1 and GLUT4 were used to compare the distribution of these
      proteins in normal and laminitic equine laminae. RESULTS: Immunohistochemistry
      with antibodies to alphaENaC, GLUT1 and GLUT4 confirmed the abundant expression
      of all 3 membrane proteins in healthy laminar keratinocytes. However, in
      laminitis, the Haematoxylin Van Gieson (HVG) technique revealed disordered
      laminar arrays and replacement with fibrous scar tissue. Immunostaining of
      laminitic samples confirmed the loss of alphaENaC, GLUT1 and GLUT4 positive
      keratinocytes. Other connective tissue cells did not stain positive for these
      proteins. CONCLUSIONS: This is the first report of alphaENaC and GLUT1/GLUT4
      protein expression in equine laminar keratinocytes, which also confirms that the
      loss of laminar structure and function in chronic laminitis is accompanied by the
      loss of laminar keratinocytes. POTENTIAL RELEVANCE: alphaENaC, GLUT1 and GLUT4
      may be used as phenotypic markers of metabolically active, differentiated equine
      laminar keratinocytes. Further in vitro studies are necessary to determine the
      effects of hypoxia, bacterial endotoxins, vasoactive amines, lactic acid and
      prostaglandins on the expression and activity of these plasma membrane
      keratinocyte markers.

PMID- 15147135
TI  - Equine laminitis: glucose deprivation and MMP activation induce dermo-epidermal
      separation in vitro.
AB  - REASONS FOR PERFORMING STUDY: Acute laminitis is characterised by hoof lamellar
      dermal-epidermal separation at the basement membrane (BM) zone. Hoof lamellar
      explants cultured in vitro can also be made to separate at the basement membrane
      zone and investigating how this occurs may give insight into the poorly
      understood pathophysiology of laminitis. OBJECTIVES: To investigate why glucose
      deprivation and metalloproteinase (MMP) activation in cultured lamellar explants
      leads to dermo-epidermal separation. METHODS: Explants, cultured without glucose
      or with the MMP activator p-amino-phenol-mercuric acetate (APMA), were subjected
      to tension and processed for transmission electron microscopy (TEM). RESULTS:
      Without glucose, or with APMA, explants under tension separated at the dermo
      epidermal junction. This in vitro separation occurred via 2 different
      ultrastructural processes. Lack of glucose reduced hemidesmosomes (HDs) numbers
      until they disappeared and the basal cell cytoskeleton collapsed. Anchoring
      filaments (AFs), connecting the basal cell plasmalemma to the BM, were unaffected
      although they failed under tension. APMA activation of constituent lamellar MMPs
      did not affect HDs but caused AFs to disappear, also leading to dermo-epidermal
      separation under tension. CONCLUSIONS: Natural laminitis may occur in situations
      where glucose uptake by lamellar basal cells is compromised (e.g. equine
      Cushing's disease, obesity, hyperlipaemia, ischaemia and septicaemia) or when
      lamellar MMPs are activated (alimentary carbohydrate overload). POTENTIAL
      RELEVANCE: Therapies designed to facilitate peripheral glucose uptake and inhibit
      lamellar MMP activation may prevent or ameliorate laminitis.

PMID- 15147137
TI  - Endotoxin-induced digital vasoconstriction in horses: associated changes in
      plasma concentrations of vasoconstrictor mediators.
AB  - REASONS FOR PERFORMING STUDY: Lipopolysaccharide (LPS) infusion reduces digital
      perfusion, but the mediators responsible remain undetermined. OBJECTIVES: To
      identify vasoconstrictor mediators released following LPS infusion and relate
      their appearance in plasma to digital blood flow alterations. METHODS: Blood flow
      in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min
      infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler
      ultrasonography. Concomitant measurements of hoof wall and coronary band surface
      temperatures (HWST and CBST) were made. Serial blood samples were collected and
      plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2)
      and endothelin measured. RESULTS: Plasma LPS concentrations reached a maximum of
      13.2 pg/ml during the infusion, followed by an increase in plasma TNFalpha
      concentration. Digital arterial and venous blood flow decreased by 43 and 63%,
      respectively; HWST and CBST similarly decreased. Systemic blood pressure remained
      unaltered. Plasma concentrations of TxB2 and 5-HT increased, coinciding with the
      onset of digital hypoperfusion. Plasma endothelin concentrations remained
      unchanged. CONCLUSIONS: The temporal relationship between the onset of digital
      hypoperfusion and increases in plasma 5-HT and TxB2 concentrations is consistent
      with these platelet-derived mediators being associated with LPS-induced
      laminitis. POTENTIAL RELEVANCE: These experimental data support the use of anti
      platelet therapy in the prevention of laminitis associated with endotoxaemic
      conditions.

PMID- 15147136
TI  - The effects of vasoactive amines found in the equine hindgut on digital blood
      flow in the normal horse.
AB  - REASONS FOR PERFORMING STUDY: Disturbances of digital blood flow are thought to
      be fundamental to the pathophysiology of acute laminitis. However, factors
      linking the initiating events in the equine hindgut with these disturbances in
      the foot remain to be determined. HYPOTHESIS: Amine compounds, formed by bacteria
      in the equine hindgut, have digital vasoconstrictor effects in vivo. METHODS:
      Tryptamine (1.6 microg/kg/min) and phenylethylamine (2.13 microg/kg/min) were
      infused i.v. into standing nonsedated horses. Digital blood flow was measured by
      Doppler ultrasound and foot surface temperature was monitored. Plasma 5
      hydroxytryptamine (5-HT) concentrations were measured by HPLC. RESULTS:
      Tryptamine and phenylethylamine infusions had no effect on systemic arterial
      blood pressure or heart rate, but caused significant decreases in digital
      arterial blood flow (mean +/- s.e. 29.2 +/- 8.5 and 18.4 +/- 6.8%, respectively).
      Both amines also caused decreases in dorsal hoof wall temperature (0.6 +/- 0.1
      and 0.5 +/- 0.1 degrees C for tryptamine and phenylethylamine, respectively) and
      concomitant increases in plasma 5-HT concentration. CONCLUSIONS: Tryptamine and
      phenylethylamine caused reduction of digital blood flow, effects which may have
      been mediated, in part, via displacement of 5-HT from platelets. POTENTIAL
      RELEVANCE: Amine compounds occurring in the equine hindgut, if released into the
      circulation following carbohydrate overload, could contribute to selective
      digital vasoconstriction. Further work in ponies and horses, with naturally
      occurring laminitis, is necessary to determine whether amines represent a
      therapeutic target in this disease.

PMID- 15147138
TI  - In vitro and in vivo studies of homocysteine in equine tissues: implications for
      the pathophysiology of laminitis.
AB  - REASONS FOR PERFORMING STUDY: Elevated plasma homocysteine (HCy) concentration is
      a risk factor for cardiovascular diseases associated with endothelial
      dysfunction, including the human digital ischaemic disease, Raynaud's phenomenon.
      HYPOTHESIS: HCy causes dysfunction of equine vascular endothelium and elevated
      plasma concentrations predispose to laminitis. OBJECTIVES: To determine 1) the
      concentration of HCy in vitro, which inhibits equine vascular endothelial cell
      function and 2) any association between risk of laminitis and plasma HCy
      concentration. METHODS: Endothelial function was studied by measuring endothelium
      dependent vasodilatory responses of the equine isolated perfused digit and basal
      nitric oxide (NO) production by cultured equine digital vein endothelial cells
      (EDVECs). Total plasma HCy (tHCy) concentrations were measured in samples
      collected in the winter and spring from normal ponies and ponies predisposed to
      laminitis. RESULTS: HCy (10 and 100 micromol/l) inhibited endothelial function
      and, at concentrations above 100 micromol/l, inhibited NO production by EDVECs.
      Plasma tHCy concentration ranged from 13 to 14.7 micromol/l. There was no effect
      of season or disease status on the concentration measured. CONCLUSIONS: In vitro,
      HCy was shown to interfere with endothelial cell function at physiologically
      relevant concentrations. No evidence was found for an association between risk of
      laminitis and high plasma concentrations of HCy. POTENTIAL RELEVANCE: Elevated
      plasma HCy concentrations could adversely affect endothelial cell function and
      mangement regimens that lead to increases in plasma HCy concentration should be
      avoided in ponies predisposed to laminitis.

PMID- 15147139
TI  - Increased expression of MAIL, a cytokine-associated nuclear protein, in the
      prodromal stage of black walnut-induced laminitis.
AB  - REASONS FOR PERFORMING STUDY: The mediators and signalling cascades important in
      the initiation of laminitis remain unclear. We therefore wanted to explore the
      genes and overall signalling mechanisms that play an important role in the
      developmental stage of laminitis. OBJECTIVE: To use a broad genomic screening
      technique to identify novel genes that are differentially regulated in the equine
      lamellae during the developmental period of laminitis. METHODS: Differential mRNA
      display (DRD) was performed to discover regulated genes, and real-time
      quantitative polymerase chain reaction (RT-qPCR) was then used to evaluate
      lamellar mRNA levels of a regulated gene (MAIL) and mediators related to that
      gene (IL-1beta and IL-6) in control horses (n = 5) and horses administered black
      walnut extract (BWE; n = 5). RESULTS: Using DRD, MAIL was identified as a
      regulated gene. RT-qPCR indicated a 4-fold increase in expression of the MAIL
      mRNA in BWE lamellae compared to controls. A 30-fold increase in IL-1beta, and a
      160-fold difference in IL-6 mRNA expression was present in BWE lamellae.
      Differences in MAIL, IL-1beta and IL-6 mRNA expression were statistically
      significant between groups (P < 0.05). CONCLUSIONS AND POTENTIAL RELEVANCE: The
      data strongly support a role for inflammatory cytokines in the developmental
      stages of laminitis, possibly inducing the vascular and metabolic alterations
      reported to occur in the affected digit. These results potentially support the
      use of anti-inflammatory drugs in horses at risk of laminitis, and warrant
      further investigation of the link between systemic disease processes associated
      with laminitis and the reported digital inflammation.

PMID- 15147140
TI  - Evaluation of urinary TBARS in normal and chronic laminitic ponies.

PMID- 15147141
TI  - Serum insulin concentrations in horses with equine Cushing's syndrome: response
      to a cortisol inhibitor and prognostic value.
AB  - REASONS FOR PERFORMING STUDY: Serum insulin concentration and its use as a
      prognostic indicator in horses with equine Cushing's syndrome (ECS) have been
      poorly documented. OBJECTIVES: To examine daily insulin variations in horses with
      ECS and the effect of treatment using trilostane, a competitive inhibitor of
      3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship
      between baseline serum insulin concentration and survival in horses with ECS.
      METHODS: Basal serum insulin concentrations were measured in 20 confirmed ECS
      cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400,
      0400 and 0800 h) before treatment (Day 0) and 10 days, and 30 days and 1-2 years
      after the onset of trilostane therapy. The temporal pattern of insulin was
      analysed using a linear mixed model approach, and the prognostic value of
      measurements on Day 0 assessed using receiver-operating characteristic analysis.
      RESULTS: Horses with ECS showed a diurnal pattern of serum insulin concentration,
      highest value at 1200 h, and this pattern was not altered by treatment with
      trilostane. Furthermore, despite a mild increase of serum insulin concentrations
      after 10 days of trilostane therapy, insulin concentration was unaffected in the
      long-term. Low serum insulin concentrations at the beginning of the trial were
      significantly associated with improved survival to 1-2 years. The 1200 h sampling
      before treatment had the highest prognostic value for prediction of survival with
      a sensitivity and specificity of at least 90% for serum insulin at < 62 and > 188
      microu/ml to predict survival and nonsurvival, respectively. CONCLUSIONS AND
      POTENTIAL RELEVANCE: Insulin is a useful prognostic indicator for ECS, but
      potentially large variations can occur throughout a 24 h period, indicating a
      single sample may not be representative. Serum insulin concentration did not
      increase over 1-2 years in horses receiving trilostane therapy.

PMID- 15147142
TI  - Equine laminitis: congenital, hemidesmosomal plectin deficiency in a Quarter
      Horse foal.

PMID- 15147143
TI  - How useful are haematology analyser flags?

PMID- 15147144
TI  - Intravenous immunoglobulin (IVIG): modes of action in the clinical management of
      recurrent pregnancy loss (RPL) and selected autoimmune disorders.
AB  - Recurrent pregnancy loss has been associated with autoimmune responses to
      membrane phospholipids and alloimmune reactions against paternally derived
      molecules on the trophoblast. The problem is psychologically and economically
      stressful as it undermines the capacity of some couples to reproduce and
      participate effectively in the day-to-day economic activities. This article
      reviews the adoption of intravenous immunoglobulin as a form of therapy for the
      clinical management of recurrent pregnancy loss and of selected autoimmune
      disorders. Side effects, contraindications and safety of use are discussed.

PMID- 15147146
TI  - Extracellular concentration of homocysteine in human cell lines is influenced by
      specific inhibitors of cyst(e)ine transport.
AB  - Despite the growing evidence that plasma homocysteine is a cardiovascular risk
      factor, the mechanism behind the vascular injuries is still unknown. Studies of
      the cellular uptake systems for homocysteine are scarce, but membrane
      transporters of cyst(e)ine seem to be involved. In the present study the cellular
      uptake of extracellular homocysteine in HeLa and hepatoma cell lines is
      investigated by using several different transport inhibitors for cellular uptake
      of cyst(e)ine. It is shown that systems A and Xc- are the main transport systems
      for homocysteine uptake in HeLa cells. It is also confirmed that the magnitude of
      homocysteine uptake in hepatoma cells is lower than in HeLa cells. However, in
      the presence of high amounts of extracellular homocysteine both cell types
      exhibited a high elimination of homocysteine, which was inhibited by the presence
      of inhibitors of systems A or Xc-. It is possible that there is normally a high
      turnover of homocysteine in cell cultures, which is not detected by occasional
      determinations of homocysteine concentrations. The complex pattern of
      homocysteine production, release, uptake and distribution between different cells
      in the body is important to examine further in order to possibly be able to
      modulate the elimination of homocysteine from circulation and thereby lower the
      risk of cardiovascular disease.

PMID- 15147145
TI  - Automated flagging influences the inconsistency and bias of band cell and
      atypical lymphocyte morphological differentials.
AB  - This study evaluated inter- and intra-observer variabilities of band cell and
      atypical lymphocyte differentials and the influence of instrument flagging
      information on resulting microscopic differentials. Five stained slides with a
      range of band cell counts and five with variable numbers of atypical lymphocytes
      were sent for morphological review by 30 technicians. No supplementary full blood
      cell count information was provided. Two months later, the same slides were sent,
      together with their corresponding analyzer reports comprising the full blood cell
      count, automated differentials and flags, to the same technicians. The first and
      second appraisals of band cells and variant lymphocytes both showed poor levels
      of inter-observer consistency. Observed values for all slides were very wide and
      suggested a high inherent predisposition to erroneous reporting practices.
      Analysis of category trends showed that analyzer left shift or immature
      granulocytes flags had no influence on observer band cell assessments as downward
      vs. upward category revisions were evenly balanced. The findings for atypical
      lymphocytes were, however, somewhat different. Two slides with no flags both
      showed balanced category revisions, whereas two of the three slides with atypical
      lymphocyte flags showed clear evidence of upward category revision. The third
      slide with an atypical lymphocyte flag did not show any overall category trend,
      but six of the seven observers who in the first examination recorded atypical
      lymphocyte estimates of < or = 30% revised their estimates upward when the slides
      were examined the second time. These results suggest that morphologist access to
      an analyzer report and flagging information is unlikely to affect the
      "randomness" of band cell determinations but it may induce observer bias in
      variant lymphocyte estimates.

PMID- 15147147
TI  - Generation of eight adjacent mutations in a single step using a site-directed
      mutagenesis kit.
AB  - Studies that characterize transcriptional regulatory elements involve the site
      directed mutagenesis methodology to generate deletions, insertions and point
      mutations. Commercial PCR-based system kits are widely used to introduce up to
      four base changes in a target sequence. Sequential mutagenesis experiments allow
      more than four bases to be altered. In this work, we show that the QuikChange
      site-directed mutagenesis kit developed by Stratagene, with an optimum primer
      design, can change eight adjacent bases. This approach allows us to study the
      effect of DNA sequence changes on functionality of specific sequences from gene
      target regions, including promoters, exons and introns. As a result of this
      methodology, a faster and cheaper way of introducing this number of mutations is
      achieved in a single step with only one pair of primers, thus reducing the
      possibility of potential random mutation in the rest of the target sequence.

PMID- 15147149
TI  - Impurities from polypropylene microcentrifuge tubes as a potential source of
      interference in simultaneous analysis of multiple lipid-soluble antioxidants by
      HPLC with electrochemical detection.
AB  - High-performance liquid chromatography (HPLC) with electrochemical detection was
      used to analyze lipid-soluble antioxidants and micronutrients in plasma. Small
      amounts of plasma samples are often extracted in polypropylene (PP)
      microcentrifuge tubes before HPLC analysis due to its convenience. We therefore
      investigated the effect of impurities released from different PP tubes during
      extraction on the electrochemical detection of retinol, lutein, alpha-tocopherol,
      gamma-tocopherol, retinyl palmitate, beta-carotene and total coenzyme Q10 by an
      HPLC system with a coulometric array detector (CoulArray HPLC). An array of eight
      electrical potentials and gradient elution were applied. Human plasma or
      ultrapure water were extracted in four different PP tubes. Peaks at different
      retention times with varied amounts of unknown compounds were detected from
      different PP tubes. Although all those unknown peaks could be differentiated from
      peaks of interest by the CoulArray HPLC, they caused busy chromatographs, and one
      peak had an overlap with the dominant peak of lutein. Moreover, that peak
      completely masked the lutein peak when only one oxidizing potential was applied.
      Our results suggest potential interference from PP tubes on electrochemical
      detection especially when using only one electrical potential or having poor
      separation for these antioxidants if PP tubes are not carefully tested.

PMID- 15147148
TI  - Prohepcidin accumulates in renal insufficiency.
AB  - BACKGROUND: The understanding of iron metabolism has increased substantially
      during the last decade. Several new transporters and iron regulating molecules
      have been described. Hepcidin, a small hepatic peptide has recently been proposed
      as a central mediator of dietary iron absorption. We have investigated the
      relationship between prohepcidin, the prohormone of hepcidin, and renal function
      and iron status. METHODS: Forty six patients, referred for 51Cr-EDTA clearance
      were included in this study. Renal function was assessed by determination of
      serum creatinine, creatinine clearance, serum cystatin C and serum beta-trace
      protein. Iron status was evaluated by determination of serum iron, transferrin,
      transferrin saturation and serum ferritin. All determinations were performed
      using commercial reagents (Roche Diagnostics, Dade Behring). Serum prohepcidin
      was determined using an ELISA kit. RESULTS: Serum prohepcidin was found to
      correlate with 51Cr-EDTA clearance (r = -0.44; p = 0.005), creatinine clearance,
      serum creatinine, beta-trace protein and cystatin C. No significant relationship
      was observed between serum prohepcidin concentrations and red cell count,
      hemoglobin concentration or hematocrit. No significant correlation was found in
      this population between prohepcidin concentrations and iron status. CONCLUSION:
      Increased serum prohepcidin concentrations were observed with declining kidney
      function. We observed no relationship between red cell indices or iron status and
      serum prohepcidin concentrations.

PMID- 15147150
TI  - Cerebrospinal fluid tau and Abeta42 concentrations in healthy subjects:
      delineation of reference intervals and their limitations.
AB  - Many limitations and conflicting results have cast serious doubts on the validity
      of cerebrospinal fluid tau and Abeta42 levels for the biological diagnosis of
      Alzheimer's disease, particularly extreme variations of the reference limits
      found by unrelated groups as a consequence of different reference populations
      used. In this study, we addressed the issue of defining reference limits for
      cerebrospinal fluid tau and Abeta42 in healthy adult individuals. One hundred and
      five neurologically intact subjects were enrolled according to strict inclusion
      criteria, 10 of them with autopsy confirmation of brain integrity. All
      cerebrospinal fluid samples were similarly and optimally processed as were the
      dosage methods used and the statistical analyses performed. A robust correlation
      with age was demonstrated for Abeta42 but not for tau. For tau, we found that an
      upper cut-off value of 443 ng/l allowed 95% of the subjects to be correctly
      classified as normal. For Abeta42, a lower cut-off value of 90 ng/l allowed a
      correct classification of 90% of the subjects. However, a large variance of the
      reference values, partly explained by the potential contamination of the
      reference population with presymptomatic dementia patients, may limit the use of
      reference limits based on living subjects. We propose that the issue of defining
      reference limits for both cerebrospinal fluid tau and Abeta42 may ultimately be
      settled by studying large numbers of autopsy-proven neurologically intact
      individuals only.

PMID- 15147151
TI  - The influence of smoking on plasma homocysteine and cysteine levels in passive
      and active smokers.
AB  - Total plasma homocysteine (tHcy) and cysteine (tCys) levels are associated with
      cardiovascular diseases. One of the determinants that influence their levels is
      cigarette smoking. The aim of this study was to determine the relationship
      between plasma levels of both amino acids and urinary cotinine concentration as a
      reliable biomarker of tobacco smoke exposure. One hundred and seventeen
      volunteers (61 women and 56 men) aged 19-60 years (mean 40.3 +/- 11.0) were
      included in the study. The study subjects were qualified into non-smokers,
      passive smokers and active smokers based upon the urinary cotinine concentration.
      In each particular group, plasma tHcy and tCys levels were measured and evaluated
      in the whole population and separately in women and men. Statistically
      insignificant differences in plasma tHcy and tCys levels in the whole group of
      passive smokers in comparison with non-smokers were observed (11.47 vs. 10.94
      micromol/l, p=0.414, and 253.0 vs. 266.9 micromol/l, p=0.163, respectively).
      However, statistically significant differences in plasma tHcy levels (13.29 vs.
      10.94 micromol/l, p=0.011) and in plasma tCys levels (218.2 vs. 266.9 micromol/l,
      p<0.001) were found in the whole group of active smokers compared with non
      smokers. The Pearson's coefficient (r) for the correlation between plasma tHcy
      level and urinary cotinine concentration was r=0.630 (p<0.001) in the whole group
      of active smokers and r=0.480 (p=0.003) in the whole group of passive smokers.
      The correlation between plasma tCys level and urinary cotinine concentration in
      both study groups was insignificant. Similar results were obtained when
      calculated separately for men and women. The results suggest that cigarette
      smoking is a strong determinant of plasma tHcy level, but it is not a determinant
      of plasma tCys level.

PMID- 15147152
TI  - Reference change values and power functions.
AB  - Repeated samplings and measurements in the monitoring of patients to look for
      changes are common clinical problems. The "reference change value", calculated as
      zp x [2 x (CVI2 + CVA2)](1/2), where zp is the z-statistic and CVI and CVA are
      within-subject and analytical coefficients of variation, respectively, has been
      used to detect whether a measured difference between measurements is
      statistically significant. However, a reference change value only detects the
      probability of false-positives (type I error), and for this reason, a model to
      calculate the risk of missing significant changes in serial results from
      individuals (probability of false-negatives) is investigated in this work by
      means of power functions. Therefore, when an analyte is being monitored in a
      patient, power functions estimate the probability of detecting a defined real
      change by measuring the difference. Thus, when a measured difference is the same
      as the calculated reference change value, then it will be detected in only 50% of
      situations.

PMID- 15147153
TI  - A different approach to analyzing age-related HbA1c values in non-diabetic
      subjects.
AB  - Using appropriate statistical tests and taking into account the analytical
      performance of hemoglobin A1c (HbA1c) measurements, is it useful to establish
      HbA1c age-related values in non-diabetic subjects? Non-diabetic subjects (n=135,
      72 women and 63 men) from the neuromuscular department of the Pitie-Salpetriere
      Hospital (Paris) were involved in our study. Subjects were divided into two
      groups related to age: 51 patients under 50 years old and 84 subjects aged 50
      years or more. Fasting plasma glucose and HbA1c measurements were respectively
      performed by enzymatic assay using the hexokinase method and high-performance
      liquid chromatography based on the ion exchange methodology with high precision.
      We first checked the normality of HbA1c distribution using the Kolmogorov-Smirnov
      test. Then we compared mean HbA1c in the two age subgroups using the Student's t
      test. Mean HbA1c was significantly (p<0.0001) higher in the subgroup aged 50
      years or more (mean HbA1c=5.2%) than in younger subjects (mean HbA1c=5.0%). Then
      plots were drawn to check the relationship between HbA1c and age. Under the
      hypothesis of linearity, determination coefficients (R2) were calculated.
      However, considering their low values, this hypothesis must be rejected and other
      factors than age must be retained to explain HbA1c variability.

PMID- 15147154
TI  - Ratio of urinary free immunoglobulin light chain kappa to lambda in the diagnosis
      of Bence Jones proteinuria.
AB  - The aim of this study was to evaluate the diagnostic efficacy of the ratio of
      urinary free light chain (FLC) kappa to lambda (kappa/lambda ratio) for the
      detection of Bence Jones protein (BJP). Urine specimens were collected from 243
      patients suspected of having BJP. Immunofixation identified 59 BJP-positive
      specimens among them. The kappa/lambda ratios of all specimens were determined by
      FLC immunoassays and then the cut-offs for the kappa/lambda ratio were defined as
      5.5 for BJP K and 0.1 for BJP lambda by ROC curve analyses. Using the cut-offs,
      we detected abnormal kappa/lambda ratios in 51 (86%) of the 59 BJP-positives and
      11 (6%) of the 184 BJP-negatives identified by the results of immunofixation.
      High-resolution urinary protein electrophoresis (UPE), a sensitive method for BJP
      screening, showed almost equal sensitivity to the kappa/lambda ratio, detecting
      monoclonal band(s) in 52 (88%) of the 59 BJP-positives. However, in UPE analysis
      these positive specimens should be followed by redundant immunofixation analysis
      to determine the isotypes. We further evaluated the combination method of FLC
      assays with UPE that correctly diagnosed 82% of the specimens as positive or
      negative for BJP, with only two false-negative results. These results suggest
      that quantitative FLC immunoassays provide an alternative or complementary method
      for the detection of BJP.

PMID- 15147155
TI  - Influence of blood collection in plastic vs. glass evacuated serum-separator
      tubes on hormone and tumour marker levels.
AB  - Introduction of preanalytical automation in our laboratory required the use of
      plastic blood collection tubes. Because of possible interference caused by
      adsorption of components to the plastic wall and because there is virtually no
      literature on this subject, we investigated the influence of collection of serum
      in plastic tubes on the results of nearly all our immunoassays for hormones and
      tumour markers. Blood from healthy volunteers was collected simultaneously in
      glass and plastic tubes, or sera prepared from blood collected in glass tubes
      were brought into the plastic tubes under investigation. Hormone and tumour
      marker levels were measured in the pairs thus obtained. Results were analysed
      using paired t-tests or Wilcoxon signed rank tests. We found small but
      statistically significant differences (p<0.05) between glass and plastic for free
      triiodothyronine, progesterone, prolactin, prostate-specific antigen and
      pregnancy-associated plasma protein-A. Non-significant trends (0.05<p<0.15) were
      seen with alpha-foetoprotein, androstenedione, BR (an assay for carbohydrate
      antigen 15.3), human chorionic gonadotropin and testosterone. Passing and Bablok
      regression analysis, however, revealed no clinically relevant differences (slopes
      ranged from 0.89 for progesterone to 1.07 for pregnancy-associated plasma protein
      A, while intercepts were all small). We concluded that a switch to plastic blood
      collection tubes could occur without any implications for the interpretation of
      results.

PMID- 15147156
TI  - Multicenter evaluation of a new immunoassay for procalcitonin measurement on the
      Kryptor System.
AB  - We compared the manually performed LUMItest procalcitonin (PCT) assay with the
      newly developed fully mechanized Kryptor PCT assay and determined the essential
      assay characteristics of this assay. The new Kryptor PCT assay was evaluated
      according to modified NCCLS EP-10/EP-6 protocols in five different laboratories.
      Samples from 696 patients were assayed using the original LUMItest PCT assay and
      the new Kryptor PCT assay. Possible interference by hemoglobin, triglycerides and
      bilirubin was evaluated by spiking patient plasma with the appropriate
      substances. The functional assay sensitivity (FAS) was determined by analyzing
      samples with low PCT concentrations. The FAS of the new Kryptor PCT assay was
      0.04 ng/ml and the imprecision within- and between-series below 5% and below 10%,
      respectively. Within the smallest range of determination, from 0.3 ng/ml to 50
      ng/ml, common to the LUMItest PCT assay (x) and the Kryptor PCT assay (y) the
      values correlated well: y=0.64+0.94x, s.xy=2.78 ng/ml. The performance
      characteristics of the Kryptor PCT assay are fully compatible with the intended
      clinical use. The assay allows determination of PCT in a turnaround time (TAT) of
      about 20 minutes and thus is adequate for STAT analyses.

PMID- 15147157
TI  - Comparison of three commercial assays for the measurement of 17alpha
      hydroxyprogesterone (17alpha-OHPR): limitations of the quality control system.
AB  - The measurement of 17alpha-hydroxyprogesterone (17alpha-OHPR) is of value for the
      diagnosis and management of congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency. In the central laboratory from 2000 to 2002, we observed,
      using the assay from the manufacturer DSL, an elevation of the moving average of
      17alpha-OHPR concentrations and a number of adrenocorticotropic hormone (ACTH)
      stimulation tests despite the lack of any changes to the internal and external
      quality control, of which the criteria were continuously fulfilled. We studied a
      population of n=49 patients for the measurement of 17alpha-OHPR, with and without
      extraction, to evaluate the quality of different commercially available
      radioimmunoassays. The internal and external quality controls were successful in
      determining 17alpha-OHPR. An excellent measurement and correlation of 17alpha
      OHPR was expressed with the assay from the manufacturer IBL without extraction
      and from the manufacturer DSL with extraction. The quantitative determination of
      17alpha-OHPR requires adequate specificity and accuracy of the 17alpha-OHPR
      radioimmunoassays. The results show that internal and external quality control
      systems are not sufficient to resolve analytical problems described in this
      study.

PMID- 15147158
TI  - Analytical performance of the Albumin Cobalt Binding (ACB) test on the Cobas MIRA
      Plus analyzer.
AB  - Recently a new biological marker, Ischemia Modified Albumin (IMA), measured by
      the Albumin Cobalt Binding (ACB) test, was introduced for detection of myocardial
      ischemia. During ischemia, the metal binding capacity of albumin for certain
      transition metals like cobalt is reduced. The precise mechanism of action for
      producing IMA is not known but appears to be related to the production of
      reactive oxygen species that modify the metal binding sites. The ACB test is a
      quantitative assay that detects IMA by measuring the cobalt binding capacity of
      albumin in human serum. We evaluated the analytical characteristics of the ACB
      test, and reagent and specimen stability, using the Cobas MIRA Plus instrument.
      Coefficients of variation for within-run and between-run assays were <4%. No
      significant interference was observed for concentrations of triglycerides and
      hemoglobin up to 7 mmol/l and 3.8 g/l, respectively. No interference was apparent
      with bilirubin. Measures from paired samples of heparinized plasma and serum were
      not equivalent. The assay is validated for commercial use with serum, therefore
      our study reported results for serum specimens only. All assays were completed
      within 5 hours after blood withdrawal. The one-sided upper 95th percentile,
      calculated for the ACB test in 150 healthy subjects, was 87.00 U/ml. There was no
      observed difference between men and women or with age. We conclude that the ACB
      test adapted on the Cobas MIRA Plus analyzer is satisfactory, but strict
      attention to sample handling procedures is necessary to maintain stability of the
      analyte.

PMID- 15147159
TI  - Quality assurance issues regarding chemical urinalysis.

PMID- 15147160
TI  - In vitro mineralization of gelatin-polyacrylic acid complex matrices.
AB  - Gelatin-polyacrylic acid (gel-PAA) matrices were obtained by slow diffusion of
      polyacrylic acid into gelatin gels. The matrices were submitted to uniaxial
      stretching, which induces a preferential orientation of the collagen molecules,
      and used as biomimetic substrates for the nucleation of hydroxyapatite from
      simulated body fluid (SBF). The relative amount of hydroxyapatite deposited from
      1.5SBF increases as a function of polyelectrolyte content in the matrices, up to
      about 30 wt%. In the absence of PAA, the inorganic phase is laid down on the
      surface of the gelatin matrices as hemispherical aggregates. At variance,
      hydroxyapatite deposition in the gel-PAA composite matrices at relatively low PAA
      content occurs preferentially in the spaces between the layers on the surface of
      the matrices and displays a tablet-like morphology. At high polyelectrolyte
      concentration, an almost uniform layer of hydroxyapatite covers the whole surface
      of the matrices. The preferential orientation of the (002) hydroxyapatite
      reflection indicates a close relationship between the inorganic crystals and the
      collagen molecules.

PMID- 15147161
TI  - Molecularly imprinted bioartificial membranes for the selective recognition of
      biological molecules.
AB  - Membranes of a synthetic (poly(ethylene-co-vinyl alcohol), Clarene) and a
      biological (dextran) polymer, imprinted with alpha-amylase, of different
      compositions were prepared by the phase-inversion process. Membrane morphologies
      were shown to be dependent on the synthetic-biological components composition.
      The removal of the template from the membranes was performed by extraction with
      water, while an aqueous solution of alpha-amylase was permeated across the
      membranes under pressure to obtain the rebinding of the template. The selectivity
      of alpha-amylase-imprinted membranes was investigated by the same uptake
      experiment using pepsin, albumin and amyloglucosidase, and the rebinding of these
      proteins was compared with that of the print molecule. Before and after template
      extraction and after the rebinding experiment, kinetic measurements of the
      imprinting molecule were conducted to estimate the activity of the enzyme
      immobilised in the polymer matrix. Results obtained revealed that the immobilised
      enzyme maintains a good functionality while in the membrane compared to the free
      enzyme and the imprinted 'bioartificial' dextran and Clarene membranes, obtained
      by the phase-inversion method, can establish efficient interaction with alpha
      amylase as template molecule, as confirmed by the fair selectivity in rebinding
      tests.

PMID- 15147162
TI  - Preparation and characterization of ibuprofen-loaded poly(lactide-co
      glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes.
AB  - Ibuprofen-loaded composite membranes composed of poly(lactide-co-glycolide)
      (PLGA) and poly(ethylene glycol)-g-chitosan (PEG-g-CHN) were prepared by
      electrospinning. The electrospun membranes were characterized by scanning
      electron microscopy (SEM), differential scanning calorimetry (DSC), mechanical
      evaluation and contact angle measurements. Shrinkage behavior of the membrane in
      buffer at 37 degrees C was also evaluated. It was found that PLGA glass
      transition temperature (Tg) decreased with increasing PEG-g-CHN content in the
      composite membranes, which results in a decrease in tensile stress at break but
      an increase in tensile strain of the membranes. The degree of shrinkage of these
      composite membranes decreased from 76 to only 3% when the PEG-g-CHN content in
      the membranes increased from 10 to 30%. The presence of PEG-g-CHN significantly
      moderated the burst release rate of ibuprofen from the electrospun PLGA
      membranes. Moreover, ibuprofen could be conjugated to the side chains of PEG-g
      CHN to prolong its release for more than two weeks. The sustained release
      capacity of the PLGA/PEG-g-CHN composite membranes, together with their compliant
      and stable mechanical properties, renders them ideal matrices for atrial
      fibrillation.

PMID- 15147163
TI  - Flow-stress-induced discrimination of a K-ras point mutation by sandwiched
      polymer microsphere-enhanced surface plasmon resonance.
AB  - The highly sensitive detection of a K-ras point mutation with the aid of DNA
      carrying microspheres as a flow-stress receptor is proposed at the surface of a
      surface plasmon resonance (SPR) biosensor. Single-stranded DNAs were immobilized
      onto epoxy-group-derivatized gold surfaces and the hybridization of DNA targets
      was monitored. The subsequent interaction with DNA-carrying micospheres enhanced
      the SPR response. The increase of flow rate during the event of dissociation
      changed the amount of detachment of the DNA-carrying microspheres for the
      mismatched pair. In addition, the viscosity was changed by addition of glycerol
      to the buffer. The increase of shear stress from the flow resulted in detachment
      of DNA-carrying microspheres hybridized with the mismatched sequence and
      increased the ability to discriminate a point mutation. This is a new method
      which not only increases the lower detection limit of evanescent wave-based
      biosensors, but also the ability to discriminate a point mutation which is a
      critical factor for ultrasensitive DNA detection in flow devices.

PMID- 15147164
TI  - Dynamics of cellular entry and drug delivery by dendritic polymers into human
      lung epithelial carcinoma cells.
AB  - Dendrimers and hyperbranched polymers are emerging as potentially ideal drug
      delivery vehicles because they provide a significant amount of tailorability and
      a large density of functional groups. This study explores the dynamics of
      cellular entry of dendrimers and hyperbranched polymers alone, and in the
      complexed form with ibuprofen, into A549 human lung epithelial carcinoma cells
      using UV/Vis spectroscopy, flow cytometry and fluorescence microscopy. Both
      dendrimers and hyperbranched polymers appear to enter these cells rapidly. The
      polyamidoamine (PAMAM) dendrimers, with NH2 and OH end functionalities appear to
      enter cells (in approx. 1 h) faster than the hyperbranched polyol (OH
      functionality) (in approx. 2 h). Cellular entry of PAMAM-NH2 was detected as
      early as 5 min. All branched polymers and their ibuprofen complexes entered A549
      lung epithelial cells rapidly when compared to the pure drug. The drug payload
      was about 50% by weight in the complexes formed by PAMAM-NH2 dendrimers and was
      about 30% in the encapsulated form for Polyol-OH and PAMAM-OH. The complexation
      and encapsulation of ibuprofen with the polymers appear to facilitate rapid
      cellular entry of ibuprofen. The anti-inflammatory effect of the polymer
      complexed drug was demonstrated by more rapid suppression of COX-2 mRNA levels
      than that achieved by the pure drug. This suggests that these dendritic polymers
      can act as efficient drug carriers, delivering high 'payloads' of drug even with
      complexation and encapsulation.

PMID- 15147165
TI  - LF-NMR water self-diffusion and relaxation time measurements of hydrogel contact
      lenses interacting with artificial tears.
AB  - The different swelling properties of ionic and non-ionic lenses, immersed in
      sodium chloride or artificial tears, were investigated by Low-Field Nuclear
      Magnetic Resonance (LF-NMR) through relaxation time and self-diffusion
      coefficient measurements. A new model was developed to estimate the water self
      diffusion coefficient inside the lenses, the results of which revealed a
      different mechanism of interaction for ionic versus non-ionic materials with
      artificial tears. The consequence of this finding suggests clinical implications.

PMID- 15147166
TI  - Utilization of a sol-gel method for encapsulation of doxorubicin.
AB  - The sol-gel pre-doping method was used to encapsulate doxorubicin in silica gels
      and optimum conditions of preparation of drug-loaded gel were established,
      ensuring both reproducible and effective results of quantitative encapsulation of
      doxorubicin and its gradual but complete release. Doxorubicin was encapsulated in
      polysiloxane polymers using the method based on sol-gel encapsulation without a
      catalyst, with an acid catalyst (HCl) and a base catalyst (NH3). The time of
      gelation of the gel loaded with doxorubicin, encapsulation efficiency of the drug
      and the degree of release of the drug from the gel are all affected by the kind
      of catalyst (acidic or basic) or its absence at the gel preparation stage, and
      the temperature of the gelation process. The time of sol gelation when using the
      NH3 or HCl catalyst was 9 days at 21 degrees C, 2 days at 30 degrees C and 1.5
      days at 37 degrees C, while for the gel prepared without a catalyst it was 90
      days at 21 degrees C, 75 days at 30 degrees C and 70 days at 37 degrees C. The
      efficiency of doxorubicin encapsulation was 99.5 +/- 0.5% (w/w) for acid
      catalyzed gel, 98.9 +/- 1.01% (w/w) for base-catalyzed gel and 86.4 +/- 11.6%
      (w/w) for non-catalyzed gel. A 100% (w/w) release of doxorubicin by diffusion
      through pores was found only in the case of base-catalyzed gel after a 140-h
      incubation time. For acid-catalyzed gel and non-catalyzed gel, the total amounts
      of released doxorubicin after 140 h of incubation were 3-5% (w/w) and 9-11%
      (w/w), respectively. The stability of doxorubicin encapsulated in the three kinds
      of gel matrices was found to be improved compared to the stability of a free form
      of the drug in solution.

PMID- 15147167
TI  - Competitive plasma protein adsorption on modified polymer surfaces monitored by
      quartz crystal microbalance technique.
AB  - This paper describes the effects of photochemical modifications of polymer
      surfaces on the competitive adsorption of serum proteins and cell adhesion
      (hepatoma cell line HepG2, L929 fibroblasts and others). The UV modification of
      polystyrene, poly(methylmethacrylate) and polycarbonate alters the physico
      chemical properties of these polymers in a way that allows the formation of
      micrometer scaled cellular patterns in vitro by controlling the composition and
      properties of the protein adsorbate. Using a quartz microbalance technique,
      capable to extract viscoelastic data in addition to the mass load of the polymer
      coated sensor, we have demonstrated the importance of the thickness and the
      viscosity of an albumin adsorbate for the observed cell adhesion in vitro. The
      quantity and viscosity of surface bound albumin on polystyrene, being a cell
      repellent material in its native state, is lowered when the surface is exposed to
      UV of lambda = 185 nm in air prior to the contact with albumin solutions or cell
      culture media. This promotes the deposition of cell adhesion proteins and
      explains the observed cell patterns. Apart from this special application the
      described quartz microbalance with dissipation monitoring provides a useful tool
      for general biocompatibility studies based on surface phenomena of biomaterials.

PMID- 15147168
TI  - Structural basis of single-stranded RNA recognition.
AB  - RNA is an ancient and highly versatile molecule that plays fundamental roles in
      all living organisms. Its molecular functions range from being a mediator of
      genetic information to the regulation of essential cellular processes. These
      functions are often accomplished in close association with RNA binding proteins.
      Over the past few years, a considerable number of high-resolution three
      dimensional structures of important protein-RNA complexes have been determined.
      Here, we wish to discuss recent examples and highlight principles and distinct
      features of single-stranded RNA recognition by conserved RNA binding domains.

PMID- 15147169
TI  - Toward ideal (trans)esterification by use of fluorous distannoxane catalysts.
AB  - 1,3-Disubstituted tetrakis(fluoroalkyl)distannoxanes, (XR(2)SnOSnR(2)Y)(2) (R =
      C(6)F(13)C(2)H(4) and C(4)F(9)C(2)H(4)), are highly fluorophilic and exhibit
      large partition coefficients in favor of fluorocarbon solvents over common
      organic solvents due to a double-layered structure where the stannoxane core is
      covered by fluoroalkyl groups. Under catalysis of these Lewis acids, fluorous
      technology allows novel transesterification and esterification in which a 100%
      yield of the desired esters is achievable with reactants in a strict 1:1 ratio.
      The catalysts are recovered from the fluorous phase quantitatively. More
      practically, the catalyst in fluorocarbon solution can be recycled for use in the
      next reaction repeatedly.

PMID- 15147170
TI  - Beta-sultams-mechanism of reactions and use as inhibitors of serine proteases.
AB  - beta-Sultams are reactive sulfonyl analogues of beta-lactams and show enormous
      rate enhancements over analogous reactions of sulfonamides. N-Acyl beta-sultams
      undergo S-N rather than C-N fission, although alpha-alkenyl substituents direct
      nucleophilic attack to the acyl center. They also inactivate serine enzymes such
      as elastase and beta-lactamase by sulfonylation of the active site serine.
      Structure-activity relationships are used to identify differences in transition
      state structures.

PMID- 15147171
TI  - Communication pathways between the nucleotide pocket and distal regulatory sites
      in protein kinases.
AB  - Protein kinases control many cellular processes via the ATP-dependent
      phosphorylation of specific amino acids on target proteins. Despite the
      availability of the three-dimensional structures of a variety of protein kinases,
      it has been particularly difficult to explain how noncatalytic domains removed
      from the active site regulate catalytic function. In this review, we describe how
      solution methodologies complement the available structural data and help explain
      how protein kinases may utilize medium-to-long-range effects to regulate
      substrate phosphorylation. For illustration, two protein kinases, cAMP-dependent
      protein kinase and the C-terminal Src kinase, are presented as paradigms for the
      serine/threonine- and tyrosine-specific families. While active-site residues
      provide an optimal environment for fast phosphoryl group transfer in these and
      other kinases, the overall rate of protein phosphorylation is limited by
      nucleotide binding and associated structural changes. Hydrogen-deuterium exchange
      studies reveal that nucleotide binding induces changes that radiate from a
      central structural assembly composed of the catalytic loop, glycine-rich loop,
      and helix alpha C to unique peripheral regions inside and outside the kinase
      core. This collection of conserved and unique elements delivers information from
      the active site to distal regions and possibly provides information flow back to
      the active site. This "push-pull" hypothesis offers a means for understanding how
      protein kinases can be regulated by protein-protein interactions far from the
      active site.

PMID- 15147172
TI  - Aqueous RAFT polymerization: recent developments in synthesis of functional water
      soluble (co)polymers with controlled structures.
AB  - Reversible addition-fragmentation chain transfer (RAFT) polymerization has been
      the focus of intensive research over the past few years since this methodology
      allows the synthetic tailoring of macromolecules with complex architectures
      including block, graft, comb, and star structures with predetermined molecular
      weight, terminal functionality, and narrow molecular weight distribution. In this
      paper we recount significant milestones in achieving controlled free radical
      homopolymerization and block copolymerization of water-soluble and amphiphilic
      monomers including nonionic, cationic, anionic, and zwitterionic species. It is
      shown that under aqueous conditions, control of homopolymerization and further
      blocking to extend the molecular weight or to produce precisely structured block
      copolymers require not only careful selection of reagents (initiator, chain
      transfer agent, and monomer) but also regulation or elimination of hydrolysis of
      the omega-terminal thiocarbonylthio functionality. The technological potential of
      such systems is illustrated for the stimuli (pH) reversible micellization of
      amphiphilic block copolymers and for stabilization and stimuli responsive
      aggregation of gold nanoparticles bearing covalently tethered co(polymers). Given
      the advantages of RAFT over other controlled free radical techniques for
      preparation of water-soluble architectures, it may be anticipated that this
      technology will be at the forefront of nano- and microscale self-assembly in
      electronics and biotechnology.

PMID- 15147173
TI  - Small is different: shape-, size-, and composition-dependent properties of some
      colloidal semiconductor nanocrystals.
AB  - As the size of material becomes equal to or falls below the nanometer length
      scale that characterizes the motion of its electrons and thus its properties, the
      latter become sensitive not only to the size but also to the shape and
      composition of the particles. In this Account, we describe the changes of some
      interesting properties in different colloidal semiconductor nanoparticles, such
      as the electronic relaxation rates as spherical nanoparticles change to nanorods,
      and the changes in the structure or size of very small nanoparticles upon
      adsorbing strongly bound molecules. We have also determined and explained the
      difference in the interfacial crossing rates of electrons and holes in a
      composite nanostructure.

PMID- 15147174
TI  - Bond strengths of toluenes, anilines, and phenols: to hammett or not.
AB  - The Hammett equation correlates the effects of Y on many different chemical
      properties of YC(6)H(4)ZX families of compounds. One of the most surprising is
      that the Z-X bond dissociation enthalpy (BDE), a homolytic property, can be
      correlated for some 4-YC(6)H(4)ZX families with electrophilic substituent
      constants, sigma(p)(+)(Y), which were largely derived from the rates of the
      heterolytic S(N)1 solvolyses of para-substituted cumyl chlorides. Although there
      is no Hammett correlation of the C-X BDEs in 4-YC(6)H(4)CH(2)X (X = H, halide,
      OPh) families, there are good correlations of N-X BDEs with sigma(p)(+)(Y) in 4
      YC(6)H(4)NHX (X = H, CH(3), OH, F) and excellent correlations of O-X BDEs with
      sigma(p)(+)(Y) in 4-YC(6)H(4)OX (X = H, CH(3), CH(2)Ph) families. The reasons for
      this varied behavior are discussed.

PMID- 15147176
TI  - Conformation and dynamics of ribosomal stalk protein L12 in solution and on the
      ribosome.
AB  - During translation, the ribosome and several of its constituent proteins undergo
      structural transitions between different functional states. Protein L12, present
      in four copies in prokaryotic ribosomes, forms a flexible "stalk" with key
      functions in factor-dependent GTP hydrolysis during translocation. Here we have
      used heteronuclear NMR spectroscopy to characterize L12 conformation and dynamics
      in solution and on the ribosome. Isolated L12 forms a symmetric dimer mediated by
      the N-terminal domains (NTDs), to which each C-terminal domain (CTD) is connected
      via an unstructured hinge segment. The overall structure can be described as
      three ellipsoids joined by flexible linkers. No persistent contacts are seen
      between the two CTDs, or between the NTD and CTD in the L12 dimer in solution. In
      the (1)H-(15)N HSQC spectrum of the Escherichia coli 70S ribosome, a single set
      of cross-peaks are observed for residues 40-120 of L12, the intensities of which
      correspond to only two of four protein copies. The structure of the CTDs observed
      on the ribosome is indistinguishable from that of isolated L12. These results
      indicate that two CTDs with identical average structures are mobile and extend
      away from the ribosome, while the other two copies most likely interact tightly
      with the ribosome even in the absence of translational factors.

PMID- 15147175
TI  - Evolution of photosynthesis: time-independent structure of the cytochrome b6f
      complex.
AB  - Structures of the cytochrome b(6)f complex obtained from the thermophilic
      cyanobacterium Mastigocladus laminosus and the green alga Chlamydomonas
      reinhardtii, whose appearance in evolution is separated by 10(9) years, are
      almost identical. Two monomers with a molecular weight of 110,000, containing
      eight subunits and seven natural prosthetic groups, are separated by a large
      lipid-containing "quinone exchange cavity". A unique heme, heme x, that is five
      coordinated and high-spin, with no strong field ligand, occupies a position close
      to intramembrane heme b(n). This position is filled by the n-side bound quinone,
      Q(n), in the cytochrome bc(1) complex of the mitochondrial respiratory chain. The
      structure and position of heme x suggest that it could function in ferredoxin
      dependent cyclic electron transport as well as being an intermediate in a quinone
      cycle mechanism for electron and proton transfer. The significant differences
      between the cyanobacterial and algal structures are as follows. (i) On the n
      side, a plastoquinone molecule is present in the quinone exchange cavity in the
      cyanobacterial complex, and a sulfolipid is bound in the algal complex at a
      position corresponding to a synthetic DOPC lipid molecule in the cyanobacterial
      complex. (ii) On the p-side, in both complexes a quinone analogue inhibitor, TDS,
      passes through a portal that separates the large cavity from a niche containing
      the Fe(2)S(2) cluster. However, in the cyanobacterial complex, TDS is in an
      orientation that is the opposite of its position in the algal structure and bc(1)
      complexes, so its headgroup in the M. laminosus structure is 20 A from the
      Fe(2)S(2) cluster.

PMID- 15147177
TI  - Small alcohols destabilize the KcsA tetramer via their effect on the membrane
      lateral pressure.
AB  - Previously, it was shown that the tetrameric potassium channel KcsA when present
      in a lipid bilayer can be dissociated by trifluoroethanol [van den Brink-van der
      Laan, E., et al. (2004) Biochemistry 43, 4240-4250]. Here, we demonstrate that
      this is a general property of small alcohols. We found that small alcohols
      dissociate the KcsA tetramer, at a concentration that depends on their membrane
      affinity. Importantly, the efficiency of the alcohol-induced tetramer
      dissociation was found to correlate with the efficiency of both alcohol-induced
      bilayer leakage and acyl chain disordering. Our data suggest that the ability of
      small alcohols to induce KcsA tetramer dissociation and to function as
      anesthetics depends on their effect on the membrane lateral pressure.

PMID- 15147178
TI  - Mediation by indole analogues of electron transfer during oxygen activation in
      variants of Escherichia coli ribonucleotide reductase R2 lacking the electron
      shuttling tryptophan 48.
AB  - Activation of dioxygen by the carboxylate-bridged diiron(II) cluster in the R2
      subunit of class I ribonucleotide reductase from Escherichia coli results in the
      one-electron oxidation of tyrosine 122 (Y122) to a stable radical (Y122*). A key
      step in this reaction is the rapid transfer of a single electron from a near
      surface residue, tryptophan 48 (W48), to an adduct between O(2) and diiron(II)
      cluster to generate a readily reducible cation radical (W48(+)(*)) and the
      formally Fe(IV)Fe(III) intermediate known as cluster X. Previous work showed that
      this electron injection step is blocked in the R2 variant with W48 replaced by
      phenylalanine [Krebs, C., Chen, S., Baldwin, J., Ley, B. A., Patel, U.,
      Edmondson, D. E., Huynh, B. H., and Bollinger, J. M., Jr. (2000) J. Am. Chem.
      Soc. 122, 12207-12219]. In this study, we show that substitution of W48 with
      alanine similarly disables the electron transfer (ET) but also permits its
      chemical mediation by indole compounds. In the presence of an indole mediator,
      O(2) activation in the R2-W48A variant produces approximately 1 equiv of stable
      Y122* and more than 1 equiv of the normal (micro-oxo)diiron(III) product. In the
      absence of a mediator, the variant protein generates primarily altered Fe(III)
      products and only one-fourth as much stable Y122* because, as previously reported
      for R2-W48F, most of the Y122* that is produced decays as a consequence of the
      inability of the protein to mediate reductive quenching of one of the two
      oxidizing equivalents of the initial diiron(II)-O(2) complex. Mediation of ET is
      effective in W48A variants containing additional substitutions that also impact
      the reaction mechanism or outcome. In the reaction of R2-W48A/F208Y, the presence
      of mediator suppresses formation of the Y208-derived diiron(III)-catecholate
      product (which is predominant in R2-F208Y in the absence of reductants) in favor
      of Y122*. In the reaction of R2-W48A/D84E, the presence of mediator affects the
      outcome of decay of the peroxodiiron(III) intermediate known to accumulate in
      D84E variants, increasing the yield of Y122* by as much as 2.2-fold to a final
      value of 0.75 equiv and suppressing formation of a 490 nm absorbing product that
      results from decay of the two-electron oxidized intermediate in the absence of a
      functional ET apparatus.

PMID- 15147179
TI  - Use of a chemical trigger for electron transfer to characterize a precursor to
      cluster X in assembly of the iron-radical cofactor of Escherichia coli
      ribonucleotide reductase.
AB  - A key step in generation of the catalytically essential tyrosyl radical (Y122(*))
      in protein R2 of Escherichia coli ribonucleotide reductase is electron transfer
      (ET) from the near-surface residue, tryptophan 48 (W48), to a (Fe(2)O(2))(4+)
      complex formed by addition of O(2) to the carboxylate-bridged diiron(II) cluster.
      Because this step is rapid, the (Fe(2)O(2))(4+) complex does not accumulate and,
      therefore, has not been characterized. The product of the ET step is a
      "diradical" intermediate state containing the well-characterized Fe(IV)Fe(III)
      cluster, X, and a W48 cation radical (W48(+)(*)). The latter may be reduced from
      solution to complete the two-step transfer of an electron to the buried diiron
      site. In this study, a (Fe(2)O(2))(4+) state that is probably the precursor to
      the X-W48(+)(*) diradical state in the reaction of the wild-type protein (R2-wt)
      has been characterized by exploitation of the observation that in R2 variants
      with W48 replaced with alanine (A), the otherwise disabled ET step can be
      mediated by indole compounds. Mixing of the Fe(II) complex of R2-W48A/Y122F with
      O(2) results in accumulation of an intermediate state that rapidly converts to X
      upon mixing with 3-methylindole (3-MI). The state comprises at least two species,
      of which each exhibits an apparent Mossbauer quadrupole doublet with parameters
      characteristic of high-spin Fe(III) ions. The isomer shifts of these complexes
      and absence of magnetic hyperfine coupling in their Mossbauer spectra suggest
      that both are antiferromagnetically coupled diiron(III) clusters. The fact that
      both rapidly convert to X upon treatment with a molecule (3-MI) shown in the
      preceding paper to mediate ET in W48A R2 variants indicates that they are more
      oxidized than X by one electron, which suggests that they have a bound peroxide
      equivalent. Their failure to exhibit either the long-wavelength absorption (at
      650-750 nm) or Mossbauer doublet with high isomer shift (>0.6 mm/s) that are
      characteristic of the putatively mu-1,2-peroxo-bridged diiron(III) intermediates
      that have been detected in the reactions of methane monooxygenase (P or
      H(peroxo)) and variants of R2 with the D84E ligand substitution suggests that
      they have geometries and electronic structures different from those of the
      previously characterized complexes. Supporting this deduction, the
      peroxodiiron(III) complex that accumulates in R2-W48A/D84E is much less reactive
      toward 3-MI-mediated reduction than the (Fe(2)O(2))(4+) state in R2-W48A/Y122F.
      It is postulated that the new (Fe(2)O(2))(4+) state is either an early adduct in
      an orthogonal pathway for oxygen activation or, more likely, the successor to a
      (mu-1,2-peroxo)diiron(III) complex that is extremely fleeting in R2 proteins with
      the wild-type ligand set but longer lived in D84E-containing variants.

PMID- 15147180
TI  - Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the
      importance of the cyclic cystine knot.
AB  - The cyclotides constitute a recently discovered family of plant-derived peptides
      that have the unusual features of a head-to-tail cyclized backbone and a cystine
      knot core. These features are thought to contribute to their exceptional
      stability, as qualitatively observed during experiments aimed at sequencing and
      characterizing early members of the family. However, to date there has been no
      quantitative study of the thermal, chemical, or enzymatic stability of the
      cyclotides. In this study, we demonstrate the stability of the prototypic
      cyclotide kalata B1 to the chaotropic agents 6 M guanidine hydrochloride (GdHCl)
      and 8 M urea, to temperatures approaching boiling, to acid, and following
      incubation with a range of proteases, conditions under which most proteins
      readily unfold. NMR spectroscopy was used to demonstrate the thermal stability,
      while fluorescence and circular dichroism were used to monitor the chemical
      stability. Several variants of kalata B1 were also examined, including kalata B2,
      which has five amino acid substitutions from B1, two acyclic permutants in which
      the backbone was broken but the cystine knot was retained, and a two-disulfide
      bond mutant. Together, these allowed determinations of the relative roles of the
      cystine knot and the circular backbone on the stability of the cyclotides.
      Addition of a denaturant to kalata B1 or an acyclic permutant did not cause
      unfolding, but the two-disulfide derivative was less stable, despite having a
      similar three-dimensional structure. It appears that the cystine knot is more
      important than the circular backbone in the chemical stability of the cyclotides.
      Furthermore, the cystine knot of the cyclotides is more stable than those in
      similar-sized molecules, judging by a comparison with the conotoxin PVIIA. There
      was no evidence for enzymatic digestion of native kalata B1 as monitored by LC
      MS, but the reduced form was susceptible to proteolysis by trypsin,
      endoproteinase Glu-C, and thermolysin. Fluorescence spectra of kalata B1 in the
      presence of dithiothreitol, a reducing agent, showed a marked increase in
      intensity thought to be due to removal of the quenching effect on the Trp residue
      by the neighboring Cys5-Cys17 disulfide bond. In general, the reduced peptides
      were significantly more susceptible to chemical or enzymatic breakdown than the
      oxidized species.

PMID- 15147181
TI  - 3-Isopropylmalate is the major endogenous substrate of the Saccharomyces
      cerevisiae trans-aconitate methyltransferase.
AB  - The Saccharomyces cerevisiae Tmt1 gene product is the yeast homologue of the
      Escherichia coli enzyme that catalyzes the methyl esterification of trans
      aconitate, a thermodynamically favored isomer of cis-aconitate and an inhibitor
      of the citric acid cycle. It has been proposed that methylation may attenuate
      trans-aconitate inhibition of aconitase and other enzymes of the cycle. Although
      trans-aconitate is a minor endogenous substrate of the Tmt1 enzyme in extracts of
      S. cerevisiae, the major endogenous substrate has yet to be identified. We show
      here that a trimethylsilylated derivative of the major methylated endogenous
      product of Tmt1 in yeast extracts has an identical gas chromatography retention
      time and an identical electron impact mass spectrum as one of the two possible
      monomethyl ester derivatives of (2R,3S)-3-isopropylmalate. (2R,3S)-3
      Isopropylmalate is an intermediate of the leucine biosynthetic pathway that
      shares similar intermediates and reaction chemistry with the portion of the
      citric acid cycle from oxaloacetate to alpha-ketoglutarate via cis-aconitate. The
      Tmt1 methyltransferase recognizes (2R,3S)-3-isopropylmalate with similar kinetics
      as it does trans-aconitate, with respective K(m) values of 127 and 53 microM and
      V(max) values of 59 and 70 nmol min(-1) mg(-1) of protein in a Tmt1-overexpressed
      yeast extract. However, we found that isopropylfumarate, the direct homologue of
      trans-aconitate in the leucine biosynthetic pathway, was at best a very poor
      substrate for the Tmt1 yeast enzyme. Similarly, the direct homologue of 3
      isopropylmalate in the citric acid cycle, isocitrate, is also a very poor
      substrate. This apparent change in specificity between the intermediates of these
      two pathways can be understood in terms of the binding of these substrates to the
      active site. These results suggest that the Tmt1 methyltransferase may work in
      two different pathways in two different ways: for detoxification in the citric
      acid cycle and for a possibly novel biosynthetic branch reaction of the leucine
      biosynthetic pathway.

PMID- 15147182
TI  - Crystallographic and solution studies of N-lithocholyl insulin: a new generation
      of prolonged-acting human insulins.
AB  - The addition of specific bulky hydrophobic groups to the insulin molecule
      provides it with affinity for circulating serum albumin and enables it to form
      soluble macromolecular complexes at the site of subcutaneous injection, thereby
      securing slow absorption of the insulin analogue into the blood stream and
      prolonging its half-life once there. N-Lithocholic acid acylated insulin
      [Lys(B29)-lithocholyl des-(B30) human insulin] has been crystallized and the
      structure determined by X-ray crystallography at 1.6 A resolution to explore the
      molecular basis of its assembly. The unit cell in the crystal consists of an
      insulin hexamer containing two zinc ions, with two m-cresol molecules bound at
      each dimer-dimer interface stabilizing an R(6) conformation. Six covalently bound
      lithocholyl groups are arranged symmetrically around the outside of the hexamer.
      These form specific van der Waals and hydrogen-bonding interactions at the
      interfaces between neighboring hexamers, possibly representing the kinds of
      interactions which occur in the soluble aggregates at the site of injection.
      Comparison with an equivalent nonderivatized native insulin hexamer shows that
      the addition of the lithocholyl group disrupts neither the important
      conformational features of the insulin molecule nor its hexamer-forming ability.
      Indeed, binding studies show that the affinity of N-lithocholyl insulin for the
      human insulin receptor is not significantly diminished.

PMID- 15147183
TI  - Effects of protein kinase C dependent phosphorylation and a familial hypertrophic
      cardiomyopathy-related mutation of cardiac troponin I on structural transition of
      troponin C and myofilament activation.
AB  - In experiments reported here, we compared tension and thin filament Ca(2+)
      signaling in preparations containing either wild-type cardiac troponin I (cTnI)
      or a mutant cTnI with an R146G mutation [cTnI(146G)] linked to familial
      hypertrophic cardiomyopathy. Myofilament function is altered in association with
      cTnI phosphorylation by protein kinase C (PKC), which is activated in
      hypertrophy. Whether there are differential effects of PKC phosphorylation on
      cTnI compared to cTnI(146G) remains unknown. We therefore also studied cTnI and
      cTnI(146G) with PKC sites mutated to Glu, which mimics phosphorylation. Compared
      to cTnI controls, binary complexes with either cTnI(146G) or cTnI(43E/45E/144E)
      had a small effect on Ca(2+)-dependent structural opening of the N-terminal
      regulatory domain of cTnC as measured using Forster resonance energy transfer.
      However, this structural change was significantly reduced in the cTnC
      cTnI(43E/45E/144E/146G) complex. Exchange of cTnI in skinned fiber bundles with
      cTnI(146G) induced enhanced Ca(2+) sensitivity and an elevated resting tension.
      Exchange of cTnI with cTnI(43E/45E/144E) induced a depression in Ca(2+)
      sensitivity and maximum tension. However, compared to cTnI(146G),
      cTnI(43E/45E/144E/146G) had little additional effects on myofilament response to
      Ca(2+). By comparing activation of tension to the open state of the N-domain of
      cTnC with variations in the state of cTnI, we were able to provide data
      supporting the hypothesis that activation of cardiac myofilaments is tightly
      coupled to the open state of the N-domain of cTnC. Our data also support the
      hypothesis that pathological effects of phosphorylation are influenced by
      mutations in cTnI.

PMID- 15147184
TI  - Solution structure of Eucommia antifungal peptide: a novel structural model
      distinct with a five-disulfide motif.
AB  - The three-dimensional structure in aqueous solution of Eucommia antifungal
      peptide 2 (EAFP2) from Eucommia ulmoides Oliv was determined using (1)H NMR
      spectroscopy. EAFP2 is a newly discovered 41-residue peptide distinct with a five
      disulfide cross-linked motif. This peptide exhibits chitin-binding activity and
      inhibitory effects on the growth of cell wall chitin-containing fungi and chitin
      free fungi. The structure was calculated by using torsion angle dynamic simulated
      annealing with a total of 614 distance restraints and 16 dihedral restraints
      derived from NOESY and DQF-COSY spectra, respectively. The five disulfide bonds
      were assigned from preliminary structures using a statistical analysis of
      intercystinyl distances. The solution structure of EAFP2 is presented as an
      ensemble of 20 conformers with a backbone RMS deviation of 0.65 (+/-0.13) A for
      the well-defined Cys3-Cys39 segment. The tertiary structure of EAFP2 represents
      the first five-disulfide cross-linked structural model of the plant antifungal
      peptide. EAFP2 adopts a compact global fold composed of a 3(10) helix (Cys3
      Arg6), an alpha-helix (Gly26-Cys30), and a three-strand antiparallel beta-sheet
      (Cys16-Ser18, Tyr22-Gly24, and Arg36-Cys37). The tertiary structure of EAFP2
      shows a chitin-binding domain (residues 11-30) with a hydrophobic face and a
      characteristic sector formed by the N-terminal 10 residues and the C-terminal
      segment cross-linked through the unique disulfide bond Cys7-Cys37, which brings
      all four positively charged residues (Arg6, Arg9, Arg36, and Arg40) onto a
      cationic face. On the basis of such a structural feature, the possible structural
      basis for the functional properties of EAFP2 is discussed.

PMID- 15147185
TI  - Structure of serine acetyltransferase in complexes with CoA and its cysteine
      feedback inhibitor.
AB  - Serine acetyltransferase (SAT, EC 2.3.1.30) catalyzes the CoA-dependent
      acetylation of the side chain hydroxyl group of l-serine to form O-acetylserine,
      as the first step of a two-step biosynthetic pathway in bacteria and plants
      leading to the formation of l-cysteine. This reaction represents a key metabolic
      point of regulation for the cysteine biosynthetic pathway due to its feedback
      inhibition by cysteine. We have determined the X-ray crystal structure of
      Haemophilus influenzae SAT in complexes with CoA and its cysteine feedback
      inhibitor. The enzyme is a 175 kDa hexamer displaying the characteristic left
      handed parallel beta-helix (LbetaH) structural domain of the hexapeptide
      acyltransferase superfamily of enzymes. Cysteine is bound in a crevice between
      adjacent LbetaH domains and underneath a loop excluded from the coiled LbetaH.
      The proximity of its thiol group to the thiol group of CoA derived from
      superimposed models of the cysteine and CoA complexes confirms that cysteine is
      bound at the active site. Analysis of the contacts of SAT with cysteine and CoA
      and the conformational differences that distinguish these complexes provides a
      structural basis for cysteine feedback inhibition, which invokes competition
      between cysteine and serine binding and a cysteine-induced conformational change
      of the C-terminal segment of the enzyme that excludes binding of the cofactor.

PMID- 15147186
TI  - Structural, kinetic, and mutational studies of the zinc ion environment in
      tetrameric cytidine deaminase.
AB  - The zinc-containing cytidine deaminase (CDA, EC 3.5.4.5) is a pyrimidine salvage
      enzyme catalyzing the hydrolytic deamination of cytidine and 2'-deoxycytidine
      forming uridine and 2'-deoxyuridine, respectively. Homodimeric CDA (D-CDA) and
      homotetrameric CDA (T-CDA) both contain one zinc ion per subunit coordinated to
      the catalytic water molecule. The zinc ligands in D-CDA are one histidine and two
      cysteine residues, whereas in T-CDA zinc is coordinated to three cysteines. Two
      of the zinc coordinating cysteines in T-CDA form hydrogen bonds to the conserved
      residue Arg56, and this residue together with the dipole moments from two alpha
      helices partially neutralizes the additional negative charge in the active site,
      leading to a catalytic activity similar to D-CDA. Arg56 has been substituted by a
      glutamine (R56Q), the corresponding residue in D-CDA, an alanine (R56A), and an
      aspartate (R56D). Moreover, one of the zinc-liganding cysteines has been
      substituted by histidine to mimic D-CDA, alone (C53H) and in combination with
      R56Q (C53H/R56Q). R56A, R56Q, and C53H/R56Q contain the same amount of zinc as
      the wild-type enzyme. The zinc-binding capacity of R56D is reduced. Only R56A,
      R56Q, and C53H/R56Q yielded measurable CDA activity, R56A and R56Q with similar
      K(m) but decreased V(max) values compared to wild-type enzyme. Because of
      dissociation into its inactive subunits, it was impossible to determine the
      kinetic parameters for C53H/R56Q. R56A and C53H/R56Q display increased apparent
      pK(a) values compared to the wild-type enzyme and R56Q. On the basis of the
      structures of R56A, R56Q, and C53H/R56Q an explanation is provided of kinetic
      results and the apparent instability of C53H/R56Q.

PMID- 15147187
TI  - An atomic level model for the interactions of molybdenum nitrogenase with carbon
      monoxide, acetylene, and ethylene.
AB  - A combination of density functional theory and molecular mechanics calculations
      has been used to study the possible interactions of CO, C(2)H(2), and C(2)H(4)
      with the central Fe and terminal Mo sites of the iron-molybdenum cofactor of
      nitrogenase. The most favorable binding mode for CO on the central section of the
      FeMoco appears to be end-on to a single Fe and results in a change from high to
      low spin for the ligating Fe atom. If a coordination site for CO is available on
      the Mo, this becomes the preferred CO binding site. Calculated nu(CO) infrared
      frequencies are compared with the experimental values given in the literature.
      C(2)H(2) binds weakly in a side-on orientation to a single Fe site; addition of a
      single H(+)/e(-) couple to the substrate results in spontaneous migration of the
      resulting -CH=CH(2) group from Fe to a central S atom of the cofactor. Further
      reduction liberates C(2)H(4) or alternatively can give an S=CHCH(3) intermediate,
      which then goes on to produce C(2)H(6). A model for C(2)H(2) reduction by
      nitrogenase is proposed, based on the results of the calculations and the
      extensive literature on this process.

PMID- 15147188
TI  - Solution structure and backbone dynamics of the K18G/R82E Alicyclobacillus
      acidocaldarius thioredoxin mutant: a molecular analysis of its reduced thermal
      stability.
AB  - No general strategy for thermostability has been yet established, because the
      extra stability of thermophiles appears to be the sum of different cumulative
      stabilizing interactions. In addition, the increase of conformational rigidity
      observed in many thermophilic proteins, which in some cases disappears when
      mesophilic and thermophilic proteins are compared at their respective
      physiological temperatures, suggests that evolutionary adaptation tends to
      maintain corresponding states with respect to conformational flexibility. In this
      study, we accomplished a structural analysis of the K18G/R82E Alicyclobacillus
      acidocaldarius thioredoxin (BacTrx) mutant, which has reduced heat resistance
      with respect to the thermostable wild-type. Furthermore, we have also achieved a
      detailed study, carried out at 25, 45, and 65 degrees C, of the backbone dynamics
      of both the BacTrx and its K18G/R82E mutant. Our findings clearly indicate that
      the insertion of the two mutations causes a loss of energetically favorable long
      range interactions and renders the secondary structure elements of the double
      mutants more similar to those of the mesophilic Escherichia coli thioredoxin.
      Moreover, protein dynamics analysis shows that at room temperature the BacTrx, as
      well as the double mutant, are globally as rigid as the mesophilic thioredoxins;
      differently, at 65 degrees C, which is in the optimal growth temperature range of
      A. acidocaldarius, the wild-type retains its rigidity while the double mutant is
      characterized by a large increase of the amplitude of the internal motions.
      Finally, our research interestingly shows that fast motions on the pico- to
      nanosecond time scale are not detrimental to protein stability and provide an
      entropic stabilization of the native state. This study further confirms that
      protein thermostability is reached through diverse stabilizing interactions,
      which have the key role to maintain the structural folding stable and functional
      at the working temperature.

PMID- 15147189
TI  - Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid
      protein.
AB  - The severe acute respiratory syndrome (SARS) virus belongs to the Coronaviridea
      family of viruses. Its virion encodes several proteins including a replicase and
      four structural proteins. Here we describe the three-dimensional structure of the
      N-terminal domain of the SARS coronavirus (CoV) nucleocapsid protein. The protein
      consists of a five-stranded beta sheet with a folding topology distinct from
      other RNA-binding proteins. Single-stranded RNAs bind to the protein surface at
      the junction between a flexible, positively charged beta hairpin and the core
      structure. NMR-based screening was used to identify low molecular weight
      compounds that bind to this site.

PMID- 15147191
TI  - Dissecting the binding energy epitope of a high-affinity variant of human growth
      hormone: cooperative and additive effects from combining mutations from
      independently selected phage display mutagenesis libraries.
AB  - Phage display mutagenesis is a widely used approach to engineering novel protein
      properties and is especially powerful in probing structure-function relationships
      in molecular recognition processes. The relative contributions of additive and
      cooperative binding forces and the influence of conformational diversity in
      producing a novel protein-protein interface is investigated using as a model an
      ultra-high-affinity receptor binding variant of human growth hormone (hGHv) that
      has been previously affinity matured. The modular aspect of how the mutations
      were grouped in the phage display libraries and combined allowed for a systematic
      probing of the inherent functional cross-talk between the different secondary
      structure elements that make up the remodeled hGHv binding surface. We performed
      an alanine scanning analyses of 35 hGHv residues and determined the kinetics of
      each variant by surface plasmon resonance (SPR). This analysis showed that there
      is a significant difference between the additive and cooperative binding forces
      existing among the selected residues in each library module, and the binding
      advantage of these residues is maximized over the original wild-type residue when
      in the context of the other mutations in the library. The degree to which
      residues in a particular mutagenesis library display binding cooperativity
      characteristics is generally correlated with the conformational plasticity of the
      polypeptide chain. Additionally, these cooperativity effects change when the
      mutations from one library are combined with the mutations from one or several of
      the other separate libraries. This supports the idea that significant functional
      cross-talk exists between the combined library modules that can affect the
      binding energetics of individual residues over a large distance.

PMID- 15147190
TI  - Design and chemical synthesis of a magnetic resonance contrast agent with
      enhanced in vitro binding, high blood-brain barrier permeability, and in vivo
      targeting to Alzheimer's disease amyloid plaques.
AB  - Molecular imaging is an important new direction in medical diagnosis; however,
      its success is dependent upon molecular probes that demonstrate selective tissue
      targeting. We report the design and chemical synthesis of a derivative of human
      amyloid-beta (Abeta) peptide that is capable of selectively targeting individual
      amyloid plaques in the brain of Alzheimer's disease transgenic mice after being
      intravenously injected. This derivative is based on the sequence of the first 30
      amino acid residues of Abeta with asparagyl/glutamyl-4-aminobutane residues (N
      4ab/Q-4ab) substituted at unique Asp and Glu positions and with Gd-DTPA
      aminohexanoic acid covalently attached at the N-terminal Asp. The Gd[N-4ab/Q
      4ab]Abeta30 peptide was homogeneous as shown by high-resolution analytical
      techniques with a mass of +/-4385 Da determined by electrospray ionization mass
      spectrometry. This diamine- and gadolinium-substituted derivative of Abeta is
      shown to have enhanced in vitro binding to Alzheimer's disease (AD) amyloid
      plaques and increased in vivo permeability at the blood-brain barrier because of
      the unique Asp/Glu substitutions. In addition, specific in vivo targeting to AD
      amyloid plaques is demonstrated throughout the brain of an APP, PS1 transgenic
      mouse after intravenous injection. Because of the magnetic resonance (MR) imaging
      contrast enhancement provided by gadolinium, this derivative should enable the in
      vivo MR imaging of individual amyloid plaques in the brains of AD animals or
      patients to allow for early diagnosis and also provide a direct measure of the
      efficacy of anti-amyloid therapies currently being developed.

PMID- 15147192
TI  - The human T-cell lymphotropic virus type-I dimerization initiation site forms a
      hairpin loop, unlike previously characterized retroviral dimerization motifs.
AB  - The formation of genomic RNA dimers during the retroviral life cycle is essential
      for optimal viral replication and infectivity. The sequences and RNA structures
      responsible for this interaction are located in the untranslated 5' leader RNA,
      along with other cis-acting signals. Dimer formation occurs by specific
      interaction between identical structural motifs. It is believed that an initial
      kissing hairpin forms following self-recognition by autocomplementary RNA loops,
      leading to formation of an extended stable duplex. The dimerization initiation
      site (DIS) of the deltaretrovirus human T-cell lymphotropic virus type-I (HTLV-I)
      has been previously localized to a 14-nucleotide sequence predicted to contain an
      RNA stem loop. Biochemical probing of the monomeric RNA structure using RNAse T1,
      RNAse V1, RNAse U2, lead acetate, and dimethyl sulfate has led to the generation
      of the first structural map of the HTLV-I DIS. A comprehensive data set of
      individual nucleotide modifications reveals that the structural motif responsible
      for HTLV-I RNA dimerization forms a trinucleotide RNA loop, unlike any previously
      characterized retroviral dimerization motif. Molecular modeling demonstrates that
      this can be formed by an unusual C:synG base pair closing the loop. Comparative
      phylogeny indicates that such a motif may also exist in other deltaretroviruses.

PMID- 15147193
TI  - Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and
      inhibitor specificity.
AB  - Phosphodiesterases (PDEs) are enzymes that modulate cyclic nucleotide signaling
      and as such are clinical targets for a range of disorders including congestive
      heart failure, erectile dysfunction, and inflammation. The PDE3 family comprises
      two highly homologous subtypes expressed in different tissues, and inhibitors of
      this family have been shown to increase lipolysis in adipocytes. A specific PDE3B
      (the lipocyte-localized subtype) inhibitor would be a very useful tool to
      evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and might
      become a novel tool for treatment of obesity. We report here the three
      dimensional structures of the catalytic domain of human PDE3B in complex with a
      generic PDE inhibitor and a novel PDE3 selective inhibitor. These structures
      explain the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular
      basis for inhibitor specificity, and can supply a valid platform for the design
      of improved compounds.

PMID- 15147194
TI  - Structural studies of the beta-glycosidase from Sulfolobus solfataricus in
      complex with covalently and noncovalently bound inhibitors.
AB  - Transition-state mimicry is increasingly important both to understand enzyme
      mechanism and to direct the synthesis of putative therapeutic agents. X-ray
      crystallography is able to provide vital information on the interactions between
      an enzyme and the potential inhibitor. Here we report the structures, at
      approximately 2 A resolution, of a family GH1 beta-glycosidase from the
      hyperthermophilic archaeon Sulfolobus solfataricus, in complex with both
      covalently (derived from 2-fluoro-glycosides) and noncovalently (hydroximolactam)
      bound inhibitors. The enzyme has broad specificity, accommodating both gluco- and
      galacto-configured substrates, and the crystallographic data demonstrate that the
      only difference in the way these ligands bind lies in the interactions between
      Gln18, Glu432, and Trp433, and the hydroxyl group at the O3 and O4 positions.
      Inhibition by the differently configured ligands was also shown to be extremely
      similar, with K(i) values of 1.04 and 1.08 microM for the gluco and galacto
      epimers, respectively. The noncovalently bound inhibitors have a trigonal
      anomeric carbon, adopt a (4)H(3) (half-chair) conformation, and an interaction is
      formed between O2 and the catalytic nucleophile, all of which contribute to
      (partial) mimicry of the oxocarbenium-ion-like transition state. The inhibition
      of the beta-glycosidase from S. solfataricus by hydroximolactams is discussed in
      light of the emerging work on family GH1 glycosidase inhibition by a spectrum of
      putative transition-state mimics.

PMID- 15147195
TI  - Catalysis and binding of cyclophilin A with different HIV-1 capsid constructs.
AB  - The prolyl isomerase cyclophilin A (CypA) is required for efficient HIV-1
      replication and is incorporated into virions through a binding interaction at the
      Gly-Pro(222) bond located within the capsid domain of the HIV-1 Gag precursor
      polyprotein (Pr(gag)). It has recently been shown that CypA efficiently catalyzes
      the cis/trans isomerization of Gly-Pro(222) within the isolated N-terminal domain
      of capsid (CA(N)). To address the proposal that CypA interacts with Gly-Pro
      sequences in the C-terminal domain of a mature capsid, the interaction between
      CypA and the natively folded, full-length capsid protein (CA(FL)) has been
      investigated here using nuclear magnetic resonance spectroscopy. In addition, a
      fragment of the Pr(gag) protein encoding the full-matrix protein and the N
      terminal domain of capsid (MA-CA(N)) has been used to probe the catalytic
      interaction between CypA and an immature form of the capsid. The results
      discussed herein strongly suggest that Gly-Pro(222) located within the N-terminal
      domain of the capsid is the preferential site for CypA binding and catalysis and
      that catalysis of Gly-Pro(222) is unaffected by maturational processing at the N
      terminus of the capsid.

PMID- 15147196
TI  - Roles of cysteine 161 and tyrosine 154 in the lecithin-retinol acyltransferase
      mechanism.
AB  - Lecithin-retinol acyltransferase (LRAT) catalyzes the transfer of an acyl moiety
      from the sn-1 position of lecithin to vitamin A, generating all-trans-retinyl
      esters. LRAT is a unique enzyme and is the founder member of an expanding group
      of proteins of largely unknown function. In an effort to understand the mechanism
      of LRAT action, it was of interest to assign the amino acid residues responsible
      for the two pK(a) values of 8.22 and 9.95 observed in the pH vs rate profile.
      Titrating C161 of LRAT with a specific affinity labeling agent at varying pH
      values shows that this residue has a pK(a) = 8.03. Coupled with previous studies,
      this titration reveals the catalytically essential C161 as the residue
      responsible for the ascending limb of the pH vs rate profile. Site-specific
      mutagenic experiments on the lysine and tyrosine residues of LRAT reveal that
      only the highly conserved tyrosine 154 is essential for catalytic activity. This
      residue is likely to be responsible for the pK(a) = 9.95 found in the pH vs rate
      profile. Thus, LRAT has three essential residues (C161, Y154, and H60), all of
      which are conserved in the LRAT family of enzymes.

PMID- 15147197
TI  - Role of the C-terminal tyrosine of ferredoxin-nicotinamide adenine dinucleotide
      phosphate reductase in the electron transfer processes with its protein partners
      ferredoxin and flavodoxin.
AB  - The catalytic mechanism proposed for ferredoxin-NADP(+) reductase (FNR) is
      initiated by reduction of its flavin adenine dinucleotide (FAD) cofactor by the
      obligatory one-electron carriers ferredoxin (Fd) or flavodoxin (Fld) in the
      presence of oxidized nicotinamide adenine dinucleotide phosphate (NADP(+)). The C
      terminal tyrosine of FNR, which stacks onto its flavin ring, modulates the enzyme
      affinity for NADP(+)/H, being removed from this stacking position during turnover
      to allow productive docking of the nicotinamide and hydride transfer. Due to its
      location at the substrate-binding site, this residue might also affect electron
      transfer between FNR and its protein partners. We therefore studied the
      interactions and electron-transfer properties of FNR proteins mutated at their C
      termini. The results obtained with the homologous reductases from pea and
      Anabaena PCC7119 indicate that interactions with Fd or Fld are hardly affected by
      replacement of this tyrosine by tryptophan, phenylalanine, or serine. In
      contrast, electron exchange is impaired in all mutants, especially in the
      nonconservative substitutions, without major differences between the eukaryotic
      and the bacterial FNR. Introduction of a serine residue shifts the flavin
      reduction potential to less negative values, whereas semiquinone stabilization is
      severely hampered, introducing further constraints to the one-electron-transfer
      processes. Thus, the C-terminal tyrosine of FNR plays distinct and complementary
      roles during the catalytic cycle, (i) by lowering the affinity for NADP(+)/H to
      levels compatible with steady-state turnover, (ii) by contributing to the flavin
      semiquinone stabilization required for electron splitting, and (iii) by
      modulating the rates of electron exchange with the protein partners.

PMID- 15147198
TI  - Insight into covalent flavinylation and catalysis from redox, spectral, and
      kinetic analyses of the R474K mutant of the flavoprotein subunit of p-cresol
      methylhydroxylase.
AB  - Each flavoprotein subunit (PchF) of p-cresol methylhydroxylase (PCMH) has flavin
      adenine dinucleotide (FAD) covalently tethered to Tyr384. The PCMH structure
      suggests that Arg474 in PchF is required for self-catalytic covalent
      flavinylation and for substrate oxidation. The replacement of Arg474 with Lys was
      carried out to probe the subtleties of the role of Arg474 in these processes. In
      nearly all of the aspects examined, the mutant protein showed compromised
      properties relative to the wild-type protein, including the tenacity of
      noncovalent FAD binding to the apo-protein, the rate of covalent flavinylation,
      the affinity of the covalent flavoprotein for PchC (the cytochrome subunit), the
      k(cat) for substrate oxidation, and the affinity for substrate analogues in the
      formation of FAD-charge-transfer complexes (CT complexes). Nevertheless, because
      the mutant retains these attributes, the comparison allows for an examination of
      the role of this residue in the various properties of the enzyme. A correlation
      is proposed to exist between nu(m), the frequency for the absorbance maximum of
      the CT complex with a substrate analogue, and k(cat), the steady-state rate
      constant for oxidation of p-cresol by various forms of PCMH and PchF; both nu(m)
      and k(cat) can be expressed as functions of the ionization potential of the donor
      (I(D)) and the electron affinity of the acceptor (E(A)). This correlation is a
      better predictor of the rate constant for substrate oxidation than is the
      magnitude of the redox potential, E(m,7), of the bound FAD, which was determined
      for the various mutant enzyme species and compared with those of the wild type.

PMID- 15147199
TI  - Transcriptomic and proteomic analysis of a 14-3-3 gene-deficient yeast.
AB  - BMH1 and BMH2 encode Saccharomyces cerevisiae 14-3-3 homologues whose exact
      functions have remained unclear. The present work compares the transcriptomic and
      proteomic profiles of the wild type and a BMH1/2-deficient S. cerevisiae mutant
      (bmhDelta) using DNA microarrays and two-dimensional polyacrylamide gel
      electrophoresis. It is reported here that, although the global patterns of gene
      and protein expression are very similar between the two types of yeast cells, a
      subset of genes and proteins (a total of 220 genes) is significantly induced or
      reduced in the absence of Bmh1/2p. These genes include approximately 60 elements
      that could be linked to the reported phenotypes of the bmhDelta mutant (e.g.,
      accumulation of glycogen and hypersensitivity to environmental stress) and/or
      could be the potential downstream targets of interacting partners of Bmh1/2p such
      as Msn2p and Rtg3p. Importantly, >30% of the identified genes (71 genes) were
      found to be associated with carbon (C) and nitrogen (N) metabolism and transport,
      thereby suggesting that Bmh1/2p may play a major role in the regulation of C/N
      responsive cellular processes. This study presents the first comprehensive
      overview of the genes and proteins that are affected by the depletion of Bmh1/2p
      and extends the scope of knowledge of the regulatory roles of Bmh1/2p in S.
      cerevisiae.

PMID- 15147200
TI  - The affinity of elongation factor Tu for an aminoacyl-tRNA is modulated by the
      esterified amino acid.
AB  - When different mutations were introduced into the anticodon loop and at position
      73 of YFA2, a derivative of yeast tRNA(Phe), a single tRNA body was misacylated
      with 13 different amino acids. The affinities of these misacylated tRNAs for
      Thermus thermophilus elongation factor Tu (EF-Tu).GTP were determined using a
      ribonuclease protection assay. A range of 2.5 kcal/mol in the binding energies
      was observed, clearly demonstrating that EF-Tu specifically recognizes the side
      chain of the esterified amino acid. Furthermore, this specificity can be altered
      by introducing a mutation in the amino acid binding pocket on the surface of EF
      Tu. Also, when discussed in conjunction with the previously determined
      specificity of EF-Tu for the tRNA body, these experiments further demonstrate
      that EF-Tu uses thermodynamic compensation to bind cognate aminoacyl-tRNAs
      similarly.

PMID- 15147201
TI  - Identification of specific nonbridging phosphate oxygens important for DNA
      cleavage by human topoisomerase I.
AB  - Methylphosphonate-bearing oligonucleotides are characterized by the replacement
      of one of the nonbridging oxygen atoms with a methyl group. While neutralizing
      the negative charge associated with the phosphodiester at the point of
      substitution, the methyl group also imparts chirality to the phosphorus atom.
      Herein we report the synthesis of a number of oligonucleotides containing
      isomerically pure S(p) and R(p) methylphosphonates at single positions for the
      purpose of investigating the hydrogen-bonding contacts necessary for human
      topoisomerase I function. It was possible to correlate these data to the recent X
      ray crystal structure of a truncated form of the enzyme and demonstrate a severe
      decrease of cleavage efficiency when any of the nonbridging oxygen atoms upstream
      from the cleavage site was removed. Also observed was increased cleavage for
      oligonucleotides substituted with methylphosphonates downstream from the cleavage
      site. These effects were shown to be due primarily to alteration of the binding
      of the modified DNA substrates by human DNA topoisomerase I.

PMID- 15147202
TI  - Protein phosphorylation of human brain glutamic acid decarboxylase (GAD)65 and
      GAD67 and its physiological implications.
AB  - Previously, we reported that protein phosphorylation plays an important role in
      regulating soluble l-glutamic acid decarboxylase (GAD) [Bao, J. (1995) J. Biol.
      Chem. 270, 6464-6467] and membrane-associated GAD activity [Hsu, C. C. (1999) J.
      Biol. Chem. 274, 24366-24371]. Here, we report the effect of phosphorylation on
      the two well-defined GAD isoforms, namely, GAD65 and GAD67, using highly purified
      preparations of recombinant human brain GAD65 and GAD67. GAD65 was activated by
      phosphorylation, while GAD67 was inhibited by phosphorylation. The effect of
      phosphorylation on GAD65 and GAD67 could be reversed by treatment with protein
      phosphatases. We further demonstrate that protein kinase A (PKA) and protein
      kinase C isoform epsilon are the protein kinases responsible for phosphorylation
      and regulation of GAD67 and GAD65, respectively. Direct phosphorylation of GAD65
      and GAD67 was demonstrated by incorporation of [(32)P] from [gamma-(32)P]ATP into
      purified GAD65 and GAD67 and immunoblotting assay using anti
      phosphoserine/threonine antibodies. We have identified one specific
      phosphorylation site, threonine 91 (T91), in hGAD67 that can be phosphorylated by
      PKA using MALDI-TOF. Site-directed mutation of T91 to alanine abolished PKA
      mediated phosphorylation and inhibition of GAD activity. Furthermore, mutation of
      T91 to aspartic acid or glutamic acid mimics the effect of phosphorylation. A
      model depicting the effect of phosphorylation on GAD activity upon neuronal
      stimulation is also proposed.

PMID- 15147203
TI  - Dynamics of beta2-adrenergic receptor-ligand complexes on living cells.
AB  - The agonist-induced dynamic regulation of the beta(2)-adrenergic receptor
      (beta(2)-AR) on living cells was examined by means of fluorescence correlation
      spectroscopy (FCS) using a fluorescence-labeled arterenol derivative (Alexa-NA)
      in hippocampal neurons and in alveolar epithelial type II cell line A549. Alexa
      NA specifically bound to the beta(2)-AR of neurons with a K(D) value of 1.29 +/-
      0.31 nM and of A549 cells with a K(D) of 5.98 +/- 1.62 nM. The receptor density
      equaled 4.5 +/- 0.9 microm(-2) in neurons (rho(N)) and 19.9 +/- 2.0 microm(-2) in
      A549 cells (rho(A549)). Kinetic experiments revealed comparable on-rate constants
      in both cell types (k(on) = 0.49 +/- 0.03 s(-1) nM(-1) in neurons and k(on) =
      0.12 +/- 0.02 s(-1) nM(-1) in A549 cells). In addition to the free ligand
      diffusing with a D(free) of (2.11 +/- 0.04) x 10(-6) cm(2)/s, in both cell types
      receptor-ligand complexes with two distinct diffusion coefficients, D(bound1)
      (fast lateral mobility) and D(bound2) (hindered mobility), were observed
      [D(bound1) = (5.23 +/- 0.64) x 10(-8) cm(2)/s and D(bound2) = (6.05 +/- 0.23) x
      10(-10) cm(2)/s for neurons, and D(bound1) = (2.88 +/- 1.72) x 10(-8) cm(2)/s and
      D(bound2) = (1.01 +/- 0.46) x 10(-9) cm(2)/s for A549 cells]. Fast lateral
      mobility of the receptor-ligand complex was detected immediately after addition
      of the ligand, whereas hindered mobility (D(bound2)) was observed after a delay
      of 5 min in neurons (up to 38% of total binding) and of 15-20 min in A549 cells
      (up to 40% of total binding). Thus, the receptor-ligand complexes with low
      mobility were formed during receptor regulation. Consistently, stimulation of
      receptor internalization using the adenylate cyclase activator forskolin shifted
      the ratio of receptor-ligand complexes toward D(bound2). Intracellular FCS
      measurements and immunocytochemical studies confirmed the appearance of
      endocytosed receptor-ligand complexes in the cytoplasm subjacent to the plasma
      membrane after stimulation with the agonist terbutaline (1 microM). This
      regulatory receptor internalization was blocked after preincubation with
      propranolol and with a cholesterol-complexing saponin alpha-hederin.

PMID- 15147204
TI  - Homodimeric mitochondrial phosphate transport protein. Transient subunit/subunit
      contact site between the transport relevant transmembrane helices A.
AB  - The three Cys of the yeast (Saccharomyces cerevisiae) mitochondrial phosphate
      transport protein (PTP) subunit were replaced with Ser. The seven mutants
      (single, double, and complete Cys replacements) were expressed in yeast, and the
      homodimeric mutant PTPs were purified from the mitochondria and reconstituted.
      The pH gradient-dependent net phosphate (Pi) transport uptake rates (initial
      conditions: 1 mM [Pi]e, pHe 6.80; 0 mM [Pi]i, pHi 8.07) catalyzed by these
      reconstituted mutants are similar to those of the wild-type protein and range
      from 15 to 80 micromol Pi/min mg PTP protein. Aerobic media inhibit only the Pi
      uptake rates catalyzed by PTPs with the conserved (yeast and bovine) Cys28. This
      inhibition in the proteoliposomes is 84-95% and can be completely reversed by
      dithiothreitol. Transport by the wild type as well as by all mutant proteins with
      Cys28 is more than 90% inhibited by mersalyl. Transport catalyzed by mutant
      proteins with only Cys300 or only Cys134 is less sensitive, and that catalyzed by
      the no Cys mutant shows 40% inhibition by mersalyl. When dithiothreitol is
      removed from purified single Cys mutant proteins, only the mutant protein with
      Cys28 appears as a homodimer in a nonreducing SDS polyacrylamide gel. Thus, the
      function relevant transmembrane helix A, with Cys 28 about equidistant from the
      two inner membrane surfaces, is in close contact with parts of transmembrane
      helix A of the other subunit in the functional homodimeric PTP. The results
      identify for the first time not only a transmembrane helix contact site between
      the two subunits of a homodimeric mitochondrial transport protein but also a
      contact site that if locked into position blocks transport. The results are
      related to two available secondary transporter structures (lactose permease,
      glycerol-3-phosphate transporter) as well as to a low resolution projection
      structure and a high resolution structure of monomers of inhibitor ADP/ATP
      carrier complexes.

PMID- 15147206
TI  - Comparative structural analysis and kinetic properties of lactate dehydrogenases
      from the four species of human malarial parasites.
AB  - Parasite lactate dehydrogenase (pLDH) is a potential drug target for new
      antimalarials owing to parasite dependence on glycolysis for ATP production. The
      pLDH from all four species of human malarial parasites were cloned, expressed,
      and analyzed for structural and kinetic properties that might be exploited for
      drug development. pLDH from Plasmodium vivax, malariae, and ovale exhibit 90-92%
      identity to pLDH from Plasmodium falciparum. Catalytic residues are identical.
      Resides I250 and T246, conserved in most LDH, are replaced by proline in all
      pLDH. The pLDH contain the same five-amino acid insert (DKEWN) in the substrate
      specificity loops. Within the cofactor site, pLDH from P. falciparum and P.
      malariae are identical, while pLDH from P. vivax and P. ovale have one
      substitution. Homology modeling of pLDH from P. vivax, ovale, and malariae with
      the crystal structure of pLDH from P. falciparum gave nearly identical
      structures. Nevertheless, the kinetic properties and sensitivities to inhibitors
      targeted to the cofactor binding site differ significantly. Michaelis constants
      for pyruvate and lactate differ 8-9-fold; Michaelis constants for NADH, NAD(+),
      and the NAD(+) analogue 3-acetylpyridine adenine dinucleotide differ up to 4
      fold. Dissociation constants for the inhibitors differ up to 21-fold. Molecular
      docking studies of the binding of the inhibitors to the cofactor sites of all
      four pLDH predict similar orientations, with the docked ligands positioned at the
      nicotinamide end of the cofactor site. pH studies indicate that inhibitor binding
      is independent of pH in the pH 6-8 range, suggesting that differences in
      dissociation constants for a specific inhibitor are not due to altered active
      site pK values among the four pLDH.

PMID- 15147205
TI  - Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated
      through autoinhibition involving the presenilin-1 exon 9 loop?
AB  - Maturation of gamma-secretase requires an endoproteolytic cleavage in presenilin
      1 (PS1) within a peptide loop encoded by exon 9 of the corresponding gene.
      Deletion of the loop has been demonstrated to cause familial Alzheimer's disease.
      A synthetic peptide corresponding to the loop sequence was found to inhibit gamma
      secretase in a cell-free enzymatic assay with an IC(50) of 2.1 microM, a value
      similar to the K(m) (3.5 microM) for the substrate C100. Truncation at either
      end, single amino acid substitutions at certain residues, sequence reversal, or
      randomization reduced its potency. Similar results were also observed in a cell
      based assay using HEK293 cells expressing APP. In contrast to small-molecule
      gamma-secretase inhibitors, kinetic inhibition studies demonstrated competitive
      inhibition of gamma-secretase by the exon 9 peptide. Consistent with this
      finding, inhibitor cross-competition kinetics indicated noncompetitive binding
      between the exon 9 peptide and L685458, a transition-state analogue presumably
      binding at the catalytic site, and ligand competition binding experiments
      revealed no competition between L685458 and the exon 9 peptide. These data are
      consistent with the proposed gamma-secretase mechanism involving separate
      substrate-binding and catalytic sites and binding of the exon 9 peptide at the
      substrate-binding site, but not the catalytic site of gamma-secretase. NMR
      analyses demonstrated the presence of a loop structure with a beta-turn in the
      middle of the exon 9 peptide and a loose alpha-helical conformation for the rest
      of the peptide. Such a structure supports the hypothesis that this exon 9 peptide
      can adopt a distinct conformation, one that is compact enough to occupy the
      putative substrate-binding site without necessarily interfering with binding of
      small molecule inhibitors at other sites on gamma-secretase. We hypothesize that
      gamma-secretase cleavage activation may be a result of a cleavage-induced
      conformational change that relieves the inhibitory effect of the intact exon 9
      loop occupying the substrate-binding site on the immature enzyme. It is possible
      that the DeltaE9 mutation causes Alzheimer's disease because cleavage activation
      of gamma-secretase is no longer necessary, alleviating constraints on Abeta
      formation.

PMID- 15147207
TI  - Nicked apomyoglobin: a noncovalent complex of two polypeptide fragments
      comprising the entire protein chain.
AB  - Limited proteolysis of the 153-residue chain of horse apomyoglobin (apoMb) by
      thermolysin results in the selective cleavage of the peptide bond Pro88-Leu89.
      The N-terminal (residues 1-88) and C-terminal (residues 89-153) fragments of
      apoMb were isolated to homogeneity and their conformational and association
      properties investigated in detail. Far-UV circular dichroism (CD) measurements
      revealed that both fragments in isolation acquire a high content of helical
      secondary structure, while near-UV CD indicated the absence of tertiary
      structure. A 1:1 mixture of the fragments leads to a tight noncovalent protein
      complex (1-88/89-153, nicked apoMb), characterized by secondary and tertiary
      structures similar to those of intact apoMb. The apoMb complex binds heme in a
      nativelike manner, as given by CD measurements in the Soret region. Second
      derivative absorption spectra in the 250-300 nm region provided evidence that the
      degree of exposure of Tyr residues in the nicked species is similar to that of
      the intact protein at neutral pH. Also, the microenvironment of Trp residues,
      located in positions 7 and 14 of the 153-residue chain of the protein, is similar
      in both protein species, as given by fluorescence emission data. Moreover, in
      analogy to intact apoMb, the nicked protein binds the hydrophobic dye 1
      anilinonaphthalene-8-sulfonate (ANS). Taken together, our results indicate that
      the two proteolytic fragments 1-88 and 89-153 of apoMb adopt partly folded states
      characterized by sufficiently nativelike conformational features that promote
      their specific association and mutual stabilization into a nicked protein species
      much resembling in its structural features intact apoMb. It is suggested that the
      formation of a noncovalent complex upon fragment complementation can mimic the
      protein folding process of the entire protein chain, with the difference that the
      folding of the complementary fragments is an intermolecular process. In
      particular, this study emphasizes the importance of interactions between
      marginally stable elements of secondary structure in promoting the tertiary
      contacts of a native protein. Considering that apoMb has been extensively used as
      a paradigm in protein folding studies for the past few decades, the novel
      fragment complementing system of apoMb here described appears to be very useful
      for investigating the initial as well as late events in protein folding.

PMID- 15147208
TI  - Tyrosine B10 inhibits stabilization of bound carbon monoxide and oxygen in
      soybean leghemoglobin.
AB  - Detailed comparisons of the carbon monoxide FTIR spectra and ligand-binding
      properties of a library of E7, E11, and B10 mutants indicate significant
      differences in the role of electrostatic interactions in the distal pockets of
      wild-type sperm whale myoglobin and soybean leghemoglobin. In myoglobin, strong
      hydrogen bonds from several closely related conformations of the distal histidine
      (His(E7)) side chain preferentially stabilize bound oxygen. In leghemoglobin, the
      imidazole side chain of His(E7) is confined to a single conformation, which only
      weakly hydrogen bonds to bound ligands. The phenol side chain of Tyr(B10) appears
      to "fix" the position of His(E7), probably by donating a hydrogen bond to the
      Ndelta atom of the imidazole side chain. The proximal pocket of leghemoglobin is
      designed to favor strong coordination bonds between the heme iron and axial
      ligands. Thus, high oxygen affinity in leghemoglobin is established by a
      favorable staggered geometry of the proximal histidine. The interaction between
      His(E7) and Tyr(B10) prevents overstabilization of bound oxygen. If hydrogen
      bonding from His(E7) were as strong as it is in mammalian myoglobin, the
      resultant ultrahigh affinity of leghemoglobin would prevent oxygen transport in
      root nodules.

PMID- 15147209
TI  - Non-muscle actin filament elongation from complexes of profilin with nucleotide
      free actin and divalent cation-free ATP-actin.
AB  - Using vertebrate cytoplasmic actin consisting of a mixture of beta and gamma
      isoforms, we previously characterized profilin and nucleotide binding to
      monomeric actin (Kinosian, H. J., et al. (2000) Biochemistry 39, 13176-13188) and
      F-actin barbed end elongation from profilin-actin (PA) (Kinosian, H. J., et al.
      (2002) Biochemistry 41, 6734-6743). Our initial calculations indicated that
      elongation of F-actin from PA was more energetically favorable than elongation of
      F-actin from monomeric actin; therefore, the overall actin elongation reaction
      scheme described by these two linked reactions appeared to be thermodynamically
      unbalanced. However, we hypothesized that the profilin-induced weakening of MgATP
      binding by actin reduces the negative free energy change for the formation of
      profilin-MgATP-actin from MgATP-actin. When this was taken into account, the
      overall reaction scheme was calculated to be thermodynamically balanced. In our
      present work, we test this hypothesis by measuring actin filament barbed end
      elongation of nucleotide-free actin (NF-A) and nucleotide-free profilin-actin (NF
      PA). We find that the free energy change for elongation of F-actin by NF-PA is
      equal to that for elongation of F-actin from NF-A, indicating energetic balance
      of the linked reactions. In the absence of actin-bound divalent cation, profilin
      has very little effect on ATP binding to actin; analysis of elongation
      experiments with divalent cation-free ATP-actin and profilin yielded an
      approximately energetically balanced reaction scheme. Thus, the data in this
      present report support our earlier hypothesis.

PMID- 15147210
TI  - Two-site binding of beta-cyclodextrin to the Alzheimer Abeta(1-40) peptide
      measured with combined PFG-NMR diffusion and induced chemical shifts.
AB  - The interactions of Alzheimer's amyloid beta-peptide with cyclodextrins were
      studied by (1)H NMR: the translational diffusion coefficient of the peptide and
      chemical shift changes were studied by the presence of variable concentrations of
      cyclodextrins. For the full-length peptide, Abeta(1-40), the combined results of
      translational diffusion and chemical shift changes are consistent with a model
      where aromatic side chains interact with beta-cyclodextrin with dissociation
      constants in the millimolar range. The diffusion data were consistent with two
      beta-cyclodextrin molecules bound per peptide. The binding occurs at two sites,
      at F(19) and/or F(20) and at Y(10), with dissociation constants K(d)(F) = 4.7 mM
      and K(d)(Y) = 6.6 mM, respectively, in 10 mM sodium phosphate, pH 7.4 and 298 K.
      Shorter Alzheimer peptide fragments were studied to measure specific affinities
      for different binding sites. The N-terminal fragment Abeta(1-9) with a putative
      binding site at F(4) does not show measurable affinity for beta-cyclodextrin. The
      fragment Abeta(12-28) has similar apparent affinity (K(d) = 3.8 mM) to beta
      cyclodextrin as the full-length peptide Abeta(1-40). Here, the diffusion data
      suggests a one-to-one stoichiometry, and the binding site is F(19) and/or F(20).
      Both diffusion results and chemical shift changes give the same affinity. A
      variant Abeta(12-28)G(19)G(20) without phenylalanines does not bind to beta
      cyclodextrin. Other potential ligands, alpha-cyclodextrin, gamma-cyclodextrin,
      nicotine, and nornicotine do not bind to the Abeta(12-28) fragment. This study
      shows that combined (1)H NMR diffusion and chemical shift changes may be used to
      quantitatively determine affinities and stoichiometries of weak interactions,
      using unlabeled ligands and hosts of comparable sizes.

PMID- 15147211
TI  - Ca2+/calmodulin-dependent activation and inactivation mechanisms of alphaCaMKII
      and phospho-Thr286-alphaCaMKII.
AB  - Thr(286) autophosphorylation is important for the role of alphaCaMKII in learning
      and memory. Phospho-Thr(286)-alphaCaMKII has been described to have two types of
      activity: Ca(2+)-independent partial activity and Ca(2+)/calmodulin-activated
      full activity. We investigated the mechanism of switching between the two
      activities in order to relate them to the physiological functioning of
      alphaCaMKII. Using a fluorometric coupled enzyme assay and smooth muscle myosin
      light chain (MLC) as substrate, we found that (1) Ca(2+)-independent activity of
      phospho-Thr(286)-alphaCaMKII represents 5.0 (+/-3.7)% of the activity measured in
      the presence of optimal concentrations of Ca(2+) and calmodulin and (2) Ca(2+) in
      the presence of calmodulin activates the enzyme with a K(m) of 137 (+/-56) nM and
      a Hill coefficient n = 1.8 (+/-0.3). In contrast, unphosphorylated alphaCaMKII
      has a K(m) for Ca(2+) in the presence of calmodulin of 425 (+/-119) nM and a Hill
      coefficient n = 5.4 (+/-0.4). Thus, the activity of phospho-Thr(286)-alphaCaMKII
      is essentially Ca(2+)/calmodulin dependent with MLC as substrate. In
      physiological terms, our data suggest that alphaCaMKII is only activated in
      stimulated neurones whereas Ca(2+)/calmodulin activation of phospho-Thr(286)
      alphaCaMKII can occur in resting cells (approximately 100 nM [Ca(2+)]). Stopped
      flow experiments using Ca(2+)/TA-cal [Ca(2+)/2-chloro-(epsilon-amino-Lys(75))-[6
      [4-(N,N-diethylamino)phenyl]-1,3,5-triazin-4-yl]calmodulin] showed that at 100 nM
      [Ca(2+)] partially Ca(2+)-saturated Ca(2+)/cal.phospho-Thr(286)-alphaCaMKII
      complexes existed. These are likely to account for the activity of the phospho
      Thr(286)-alphaCaMKII enzyme at resting [Ca(2+)]. Ca(2+) dissociation measurements
      by a fluorescent Ca(2+) chelator revealed that the limiting Ca(2+) dissociation
      rate constants were 1.5 s(-1) from the Ca(2+)/cal.alphaCaMKII and 0.023 s(-1)
      from the Ca(2+)/cal.phospho-Thr(286)-alphaCaMKII complex, accounting for the
      differences in the Ca(2+) sensitivities of the Ca(2+)/cal.alphaCaMKII and
      Ca(2+)/cal.phospho-Thr(286)-alphaCaMKII enzymes.

PMID- 15147212
TI  - Mass spectrometric analysis of posttranslational modifications of a carrot
      extracellular glycoprotein.
AB  - Expression of extracellular dermal glycoprotein (EDGP) is induced by biotic or
      abiotic stress. The amino acid sequence alignment showed that EDGP shared
      significant homology with proteins from legumes, tomato, Arabidopsis, wheat, and
      cotton. These proteins are involved in signal transduction or stress response
      systems. Most of the Cys residues in these proteins are conserved, suggesting
      that they share similar tertiary structures. Surface plasmon resonance (SPR)
      analysis shows that EDGP binds a soybean 4-kDa hormone-like peptide (4-kDa
      peptide) in vitro and reduction of EDGP decreased significantly the binding
      activity, implying that posttranslational modifications are important for its
      function. Therefore, we investigated the posttranslational modifications in EDGP
      using mass spectrometry. As the result, six disulfide bonds in EDGP were
      identified: Cys(70)-Cys(158), Cys(84)-Cys(89), Cys(97)-Cys(113), Cys(100)
      Cys(108), Cys(201)-Cys(426), and Cys(332)-Cys(378). In addition, the N-terminal
      glutamine was cyclized into pyroglutamic acid. All four putative glycosylation
      sites were occupied by N-linked glycans, which have similar masses of m/z 1171.
      Finally, measuring the mass of the native protein showed that the
      posttranslational modifications of EDGP (pI 9.5) involved only disulfide bonds, N
      terminal modification, and glycosylation.

PMID- 15147213
TI  - Engineering a thermostable human prolyl endopeptidase for antibody-directed
      enzyme prodrug therapy.
AB  - We present a new antibody-directed enzyme prodrug therapy strategy (ADEPT) based
      on a post-proline cleaving endopeptidase and prodrugs, in which cytotoxic
      moieties are linked to a proline-containing peptide. Human prolyl endopeptidase
      was expressed in Escherichia coli and purified to homogeneity. The enzyme was
      active in buffer and in human serum but was rapidly thermally inactivated by
      incubation at 37 degrees C, thus preventing applications in vivo. While prolyl
      endopeptidase display on filamentous phage abolished viral infectivity and
      prevented directed evolution strategies based on phage display, we robotically
      screened 10752 individual colonies of mutant enzymes using a fluorogenic assay to
      improve enzyme stability. A single amino acid mutation (Glu289 --> Gly) improved
      protein stability, resulting in a half-life of 16 h at 37 degrees C in phosphate
      buffer. Two prodrugs were synthesized, in which an N-protected glycine-proline
      dipeptide was covalently coupled to doxorubicin and melphalan.
      (Benzyloxycarbonyl)glycylprolylmelphalan, but not the more sterically hindered
      doxorubicin prodrug, could be efficiently activated by prolyl endopeptidase
      [specific activity = 813.3 nmol min(-1) (mg of enzyme)(-1) at 25 degrees C]. The
      melphalan prodrug was essentially nontoxic to CHO, F9 teratocarcinoma, MCF7
      breast adenocarcinoma, and p3U1 mouse myeloma cells up to millimolar
      concentrations, while prodrug incubation with the engineered prolyl endopeptidase
      mutant led to a cell killing profile superimposable to the one of melphalan. The
      prolyl endopeptidase mutant was then chemically coupled to the human antibody
      L19, specific to the EDB domain of fibronectin, a marker of angiogenesis. The
      resulting immunoconjugate retains antigen binding and enzymatic activity, thus
      opening the way to anticancer ADEPT applications.

PMID- 15147214
TI  - Translesion synthesis past estrogen-derived DNA adducts by human DNA polymerases
      eta and kappa.
AB  - Newly discovered human DNA polymerase (pol) eta and kappa are highly expressed in
      the reproductive organs, such as testis, ovary, and uterus, where steroid
      hormones are produced. Because treatment with estrogen increases the risk of
      developing breast, ovary, and endometrial cancers, miscoding events occurring at
      model estrogen-derived DNA adducts were explored using pol eta and a truncated
      form of human pol kappa (pol kappaDeltaC). These enzymes bypassed N(2)-[3
      methoxyestra-1,3,5(10)-trien-6-yl]-2'-deoxyguanosine (dG-N(2)-3MeE) and N(6)-[3
      methoxyestra-1,3,5(10)-trien-6-yl]-2'-deoxyadenosine (dA-N(6)-3MeE), which were
      embedded in site-specifically modified oligodeoxynucleotide templates.
      Quantitative analysis of base substitutions and deletions occurring at the lesion
      site showed that pol kappaDeltaC was more efficient at incorporating dCMP
      opposite the dG-N(2)-3MeE lesion than pol eta. Surprisingly, the frequency of
      translesion synthesis beyond the dC*dG-N(2)-3MeE pair was 13% of the normal dC*dG
      pair and was 4 and 6 orders of magnitude higher than that of dC*(+)-trans-dG-N(2)
      benzo[a]pyrene and dC*dG-C8-acetylaminofluorene pairs, respectively, suggesting
      that dG-N(2)-3MeE is a natural substrate for pol kappa. In contrast, the bypass
      frequency beyond the dT*dA-N(6)-3MeE pair was 7 orders of magnitude less than
      that for the normal dT*dA pair. dA-N(6)-3MeE is a more miscoding lesion than dG
      N(2)-3MeE. Pol eta promoted incorporation of dAMP and dCMP at the dA-N(6)-3MeE
      lesion, while with pol kappaDeltaC, deletions were more frequently observed,
      along with incorporation of dAMP and dCMP opposite the lesion. These observations
      were also supported by steady-state kinetic studies. When taken together, the
      properties of pol eta and kappa are consistent with the mutagenic events
      attributed to estrogen-derived DNA adducts.

PMID- 15147216
TI  - Identification of novel in vivo phosphorylation sites in high mobility group N1
      protein from the MCF-7 human breast cancer cells.
AB  - High mobility group N1 (HMGN1) protein is a member of nonhistone chromosomal
      proteins that binds more strongly with nucleosomes than with DNA. Here we report
      the identification of the sites of in vivo phosphorylation of HMGN1 isolated from
      the MCF-7 human breast cancer cells. Our results showed that four serine
      residues, i.e., Ser6, Ser85, Ser88, and Ser98, can be phosphorylated in this
      protein. To our knowledge, this is the first demonstration that each of the three
      serine residues in the acidic C-terminal region of human HMGN1 can be
      phosphorylated. The additional negative charge resulting from the phosphorylation
      of the C-terminal serine residues is expected to modulate the interaction between
      HMGN1 and other proteins, which may enhance transcription and facilitate other
      cellular functions. In addition, the phosphorylation of HMGN1 at Ser85, which
      precedes Pro86, might play an important role in cellular signaling.

PMID- 15147215
TI  - A recombinant C121S mutant of bovine beta-lactoglobulin is more susceptible to
      peptic digestion and to denaturation by reducing agents and heating.
AB  - The lipocalin beta-lactoglobulin (BLG) is the major whey protein of bovine milk
      and is homodimeric at physiological conditions. Each monomer contains two
      disulfide bonds and one cysteine at position 121 (C121). This free thiol plays an
      important role in the heat-induced aggregation of BLG and, possibly, in its
      conformational stability. We describe here the expression in the yeast Pichia
      pastoris of a mutant bovine BLG, in which C121 was changed into Ser (C121S).
      Circular dichroism and high-performance liquid chromatography experiments,
      together with the X-ray crystal structure, show that the C121S mutant retains a
      nativelike fold at both neutral and acid pH. The mutation completely blocks the
      irreversible aggregation induced by heat treatment at 90 degrees C. Compared to
      the recombinant wild-type protein, the mutant is less stable to temperature and
      disulfide reducing agents and is much more sensitive to peptic digestion.
      Moreover, its affinity for 1-anilino-8-naphthalenesulfonate is increased at
      neutral and acid pH. We suggest that the stability of the protein arising from
      the hydrophobic effect is reduced by the C121S mutation so that unfolded or
      partially unfolded states are more favored.

PMID- 15147217
TI  - Conformational substates of the oxyheme centers in alpha and beta subunits of
      hemoglobin as disclosed by EPR and ENDOR studies of cryoreduced protein.
AB  - Exposure of frozen solutions of oxyhemoglobin to gamma-irradiation at 77 K yields
      EPR- and ENDOR-active, one-electron-reduced oxyheme centers which retain the
      conformation of the diamagnetic precursor. EPR spectra have been collected for
      the centers produced in human HbO(2) and isolated alphaO(2) and betaO(2) chains,
      as well as alphaO(2)beta(Zn), alpha(Zn)betaO(2), and alphaO(2)beta(Fe(3+))
      hybrids, each in frozen buffer and in frozen glasses that form in the presence of
      glycols and sugars and also in the presence of IHP. These reveal two
      spectroscopically distinct classes of such ferriheme centers (g(1) <or= 2.25),
      denoted A and B. Averaged over many similar sites, the A-center has a rhombic EPR
      signal with a g-tensor, g(A) = [2.248(4), 2.146(1), 1.966(1)]; the B-center
      exhibits a less anisotropic EPR signal, g(B) = [2.216(3), 2.118(2), 1.966(1)].
      Early measurement had suggested that, in the cryoreduced HbO(2) tetramer, the two
      centers corresponded to the two different chains [Symons, M. C. R., and Petersen,
      R. L. (1978) Proc. R. Soc. London, Ser. B 201, 285-300]. However, the present EPR
      and ENDOR results show that the two signals instead reflect the fact that the
      parent oxyhemes exist in two major conformational substates and that this is true
      for both alphaO(2) and betaO(2) subunits: alphaO(2)(A) (minor species) and
      alphaO(2)(B) (major species); betaO(2)(A)(major species) and betaO(2)(B) (minor
      species). Similar behavior is seen for MbO(2) [Kappl, R., Hohn-Berlage, M.,
      Huttermann, J., Bartlett, N., and Symons, M. C. R. (1985) Biochim. Biophys. Acta
      827, 327-343]. The A/B g-tensors of alphaO(2) and betaO(2) chains vary little
      with the environment of the chains, while the relative populations of the
      substates depend greatly on glycols and IHP. These results suggest a quaternary
      influence on the oxyheme distal pocket of alpha chains and that the glycol
      induced changes in the substate populations of the R-state HbO(2) tetramer are
      largely associated with the alphaO(2) subunit. (1)H ENDOR spectra from the distal
      histidine proton hydrogen-bonded to the peroxo ligand show very different
      isotropic coupling for the A- and B-centers. Analysis of the spectroscopic data
      suggests that the A- and B-centers represent different orientations of the
      oxyheme O(2) ligand relative to the distal histidine. It is likely that the A and
      B conformational substates in the alphaO(2) and betaO(2) subunits differ not only
      in their tertiary structures but in their affinities for O(2).

PMID- 15147218
TI  - Anthrax protective antigen: efficiency of translocation is independent of the
      number of ligands bound to the prepore.
AB  - Heptameric anthrax protective antigen (termed prepore), which assembles at the
      mammalian cell surface, competitively binds edema factor (EF) and/or lethal
      factor (LF). It then transports them to an acidic intracellular compartment and
      mediates their translocation across the membrane to the cytosol. Steric
      constraints limit to three the number of molecules of EF and/or LF that can bind
      simultaneously to prepore. To determine whether the number of ligand molecules
      bound per heptamer affects the efficiency of translocation, we measured the low
      pH-triggered translocation of the radiolabeled protective antigen (PA(63))
      binding domain of LF ((35)S-LF(N)) across the plasma membrane of CHO-K1 cells as
      a function of the degree of saturation of the prepore. The fraction translocated
      remained constant at approximately 0.4 as (35)S-LF(N) was varied from nil through
      saturating concentrations. The same constant value was observed when we held
      (35)S-LF(N) at a saturating concentration and varied the number of functional
      ligand sites per prepore by changing the ratio of wild-type PA to a ligand
      binding mutant. Thus, prepore containing only a single ligand-binding site is
      capable of translocating its cargo as efficiently as one containing multiple
      binding sites. The results as a whole imply that heptamers with one, two, or
      three ligands bound translocate their ligands with the same efficiency,
      indicating that each ligand molecule is translocated independently from the
      others.

PMID- 15147220
TI  - Exchange of histidine spacing between Sp1 and GLI zinc fingers: distinct effect
      of histidine spacing-linker region on DNA binding.
AB  - In the DNA recognition mode of C(2)H(2)-type zinc fingers, the finger-finger
      connection region, consisting of the histidine spacing (HX(3-5)H) and linker,
      would be important for determining the orientation of the zinc finger domains. To
      clarify the influence of spacing between two ligand histidines in the DNA
      binding, we exchanged the histidine spacing between Sp1 and GLI zinc fingers,
      which have an HX(3)H-TGEKK linker (typical) and an HX(4)H-SNEKP linker
      (atypical), respectively. A significant decrease in the DNA binding affinity and
      specificity is found in Sp1-type peptides, whereas GLI-type peptides show a mild
      reduction. To evaluate the effect of the linker characteristics, we further
      designed Sp1-type mutants with an SNEKP linker. As a result, the significant
      effect of the histidine spacing in Sp1-type peptides was reduced. These results
      demonstrate that (1) the histidine spacing significantly affects the DNA binding
      of zinc finger proteins and (2) the histidine spacing and the following linker
      regions are one effective target for regulating the DNA recognition mode of zinc
      finger proteins.

PMID- 15147219
TI  - Comparison of cis and trans fatty acid containing phosphatidylcholines on
      membrane properties.
AB  - The ever-increasing amount of trans fatty acids in the human diet has been linked
      to a variety of afflictions, most notably coronary heart disease and
      arteriosclerosis. The mechanism of why the replacement of cis fatty acids with
      their trans counterparts can be detrimental to the health of an individual
      remains a mystery. Here, we compare the differences in membrane physical
      properties including molecular dynamics, lateral lipid packing, thermotropic
      phase behavior, "fluidity", lateral mobility, and permeability between model
      membranes (lipid monolayers and bilayers) composed of cis- and trans-containing
      phosphatidylcholines (PCs). The PCs tested have a total of zero, one, two, or
      four cis (oleic or linoleic) or trans (elaidic or linoelaidic) double bonds.
      These experiments all confirm the basic hypothesis that trans fatty acids produce
      membrane properties more similar to those of saturated chains than to those of
      acyl chains containing cis double bonds; i.e., cis double bonds induce much
      larger membrane perturbations than trans double bonds.

PMID- 15147223
TI  - Research to reality: applying findings to practice.

PMID- 15147222
TI  - Lumps, bumps, and things that go itch in your office!

PMID- 15147224
TI  - Access to school health services: differences between full-time and part-time
      school nurses.
AB  - This study examined differences in student access to health services between
      schools with nurses 2 days/week (n = 7) compared to schools with nurses 5
      days/week (n = 7). The study found statistically significant differences in
      numbers of nurse visits per 100 students. Of the 30 health conditions/activities
      investigated, 28 were statistically significantly higher with full-time school
      nurses than with part-time school nurses. It would be expected that 5-day/week
      nurses would be involved in health service activities 2.5 times as often as 2
      day/week nurses. However, this study found that 21 of the 30 health service
      activities in schools with 5-day/week nurses were accessed by students more often
      than the expected 2.5 times that of the schools with nurses 2 days/week. This
      suggests a significant unmet need for access to health care services in schools
      with only 2-day/week nurses.

PMID- 15147225
TI  - Adolescent smoking cessation: development of a school nurse intervention.
AB  - The purpose of this study was to examine the feasibility of a range of strategies
      to engage and to enhance secondary school nurse involvement in teenage smoking
      prevention and cessation. School nurses were willing to assist students to quit
      smoking, but they felt unprepared. Information provided by nurses involved in a
      three-stage review, pilot-testing, and trial design resulted in the development
      of a resource for nurses. This resource comprised individual student approaches
      (brief intervention based on motivational interviewing and written activities
      designed to help students examine their smoking behavior), approaches to assist
      parents (letter of support for parents of students who smoke), and school
      newsletter items. Each component of the resource was found by school nurses to be
      appropriate, useful, and complementary to their other school- wide approaches to
      assist adolescents to quit smoking. Nurses also reported an interest to expand or
      to enhance their smoking cessation role in the school.

PMID- 15147227
TI  - Using expanded individualized health care plans to assist teachers of students
      with complex health care needs.
AB  - As special education teachers have increasing numbers of students requiring
      health care procedures in their classrooms, school nurses need to help these
      teachers maintain a safe, healthy environment for their students. Part of this
      consists of having teachers know the steps to take should certain problems arise.
      This article examines the receptivity of using an expanded version of an
      individualized health care plan (IHP) to provide critical information to address
      health care problems, as well as having individualized education program (IEP)
      objectives for instructional targets identified in the IHP. The findings of this
      study indicate that a high percentage of school nurses and special education
      teachers were in favor of an expanded version of the IHP. There was also support
      for teaching students to independently or partially participate in performing
      their own health care procedures and having this instruction formalized as IEP
      objectives.

PMID- 15147226
TI  - Healthy Hands: Use of alcohol gel as an adjunct to handwashing in elementary
      school children.
AB  - Elementary school-age children are particularly vulnerable to infections. While
      handwashing is the best method of preventing infections, many elementary schools
      are housed in buildings that have barriers to effective hand hygiene. The purpose
      of this study was to determine the effectiveness of an alcohol gel as an adjunct
      to handwashing in reducing absenteeism secondary to infectious illness. Two
      hundred and fifty-three elementary school children were randomized by classroom
      into an experimental or control group. With a crossover design, all children
      participated in both groups, with a one-week washout period between phases. A 45
      minute "Germ Unit" was taught to all children as they started the experimental
      phase and a standard unit on hand hygiene was taught as they started the control
      phase. Sixty-nine children were absent due to illness while in the control group.
      Thirty-nine children became ill while in the experimental group. Alcohol gel as
      an adjunct to handwashing was shown to be effective in reducing absenteeism due
      to infectious illness by 43%.

PMID- 15147228
TI  - Talking with teens about asthma management.
AB  - Asthma is a chronic illness that affects approximately 7 million children and
      adolescents in the United States. Teens seem to be at higher risk for poor asthma
      health outcomes because of the tumultuous changes associated with adolescence.
      The purpose of this study was to explore experiences and behaviors related to the
      self-management of teens with asthma. Teens from four different high schools
      participated in one of four focus groups. Based on these discussions, the
      following themes emerged related to teens' management of their asthma: wanting to
      be normal, the unpredictability of the disease, the credibility of the teen with
      asthma, and self- management issues. Recommendations for developing education and
      management strategies for teens with asthma are discussed.

PMID- 15147229
TI  - School nurse summer institute: a model for professional development.
AB  - The components of a professional development model designed to empower school
      nurses to become leaders in school health services is described. The model was
      implemented during a 3-day professional development institute that included
      clinical and leadership components, especially coalition building, with two
      follow-up sessions in the fall and spring. Coalition building is an important
      tool to enhance the influence of the school nurse in improving the health of
      individuals, families, and communities. School nurses and nursing educators with
      expertise in the specialty of school nursing could replicate this model in their
      own regions.

PMID- 15147230
TI  - Bibliotherapy: a strategy to help students with bullying.
AB  - Use of bibliotherapy to address childhood teasing and bullying is an innovative
      approach school nurses should consider as they work to promote a healthy school
      environment. Children's books serve as a unique conduit of exchange between
      parents, teachers, and children. Bibliotherapy, using books to help people solve
      problems, involves three stages: identification, catharsis, and insight. These
      stages lend themselves well to coping with the sensitivities related to teasing
      and bullying. Salient research findings pertinent to teasing and bullying have
      made their way into the children's literature and have been well received by
      children and their families over the course of the Child Adolescent Teasing in
      Schools (CATS) book review project and web site development. After exposure to a
      fictional story about teasing and bullying, children have shared their own
      nonfictional account of this often devastating experience and have come to
      develop successful coping strategies for dealing with the teasing and bullying
      that takes place in schools nationwide.

PMID- 15147231
TI  - Health report cards: an idea whose time has come?

PMID- 15147232
TI  - Pituitary synaptic protein SNAP-25 sensitive to GnRH is necessary for LH release.
AB  - OBJECTIVE: The protein SNAP-25 is located in the plasma membrane and is known to
      participate in hormone exocytosis process. In the present work we studied the
      role of SNAP-25 on LH secretion in permeabilized adenohypophyseal cultured cells.
      The question of whether GnRH regulates SNAP-25 expression in adenohypophyseal
      cultured cells and in the adenohypophyses in vivo was also investigated. METHODS:
      In digitonin-permeabilized cells incubated with anti-SNAP-25, stimulated LH
      secretion with Ca2+ was analysed. The presence and expression of SNAP-25 in
      adenohypophyseal cultured cells incubated with GnRH and in adenohypophyses of
      orchidectomized rats with GnRH administration was studied by immunochemistry and
      immunoblotting. RESULTS: Immunochemical study revealed that SNAP-25 was present
      in cultured adenohypophyseal cells and in adenohypophysis of orchidectomized rats
      both with GnRH treatment. We found that LH secretion can be blocked by antibodies
      raised against SNAP-25 in permeabilized cells. Likewise, GnRH administration
      induced a significant decrease of SNAP-25 expression in cultured adenohypophyseal
      cells and in adenohypophysis of orchidectomized rats. CONCLUSION: Our study
      showed that SNAP-25 is present in adenohypophyses in vitro as well as in vivo and
      that is involved in LH release and that GnRH can modify its expression.

PMID- 15147233
TI  - Amelioration by active hexose correlated compound of endocrine disturbances
      induced by oxidative stress in the rat.
AB  - OBJECTIVE: Active hexose correlated compound (AHCC), an extract derived from
      fungi of Basidiomycetes family, has been found to be a potent antioxidant. Since
      the secretion of some hormones can be affected by reactive oxygen species, the
      objective of this study was to examine how ferric nitrilotriacetate (FeNTA),
      which generates hydroxyl radicals in vivo, modulates the hormone secretion and
      the effects of AHCC. METHODS: AHCC at 3 % in drinking water was given to male
      rats for one week, and the animals were decapitated at different time intervals
      after the treatment with FeNTA intraperitoneally. Serum levels of hormones
      (corticosterone, testosterone, thyroxine and triiodothyronine), adrenal ascorbic
      acid as well as changes in hepatic oxidative status were evaluated by immunoassay
      and spectrometry. RESULTS: Serum corticosterone levels increased significantly
      following FeNTA treatment, while AHCC reduced the increased levels to normal.
      Adrenal ascorbic acid levels that reflect ACTH secretion, were decreased by FeNTA
      and restored to normal by AHCC. Serum levels of testosterone and thyroxine (T4)
      decreased rapidly after FeNTA treatment, while AHCC pretreatment prevented this
      fall. Serum triiodothyroxine (T3) levels remained unchanged either by FeNTA or
      AHCC treatment. The hepatic oxidized glutathione, glutathione-related enzymes and
      also serum lipid peroxide were greatly enhanced after FeNTA treatment. All of
      these changes were restored to normal by AHCC pretreatment. CONCLUSION: FeNTA
      induces various endocrine disorders and AHCC ameliorates these effects by acting
      as an antioxidant.

PMID- 15147234
TI  - Estrus cycle-dependent action of leptin on basal and GH or IGF-I stimulated
      steroid secretion by whole porcine follicles.
AB  - OBJECTIVE: To determine the levels of leptin in the follicular fluid and using
      culture of whole ovarian follicles, to test the hypothesis that leptin may
      directly influence GH and IGF-I stimulated ovarian function. METHODS: Porcine
      follicles were recovered from ovaries during early, middle, and preovulatory
      stage of the follicular phase of the estrus cycle. They were cultured in the
      presence of the recombinant ovine leptin (oLEP) added either alone or with oGH or
      hIGF-I. Steroid concentrations in the media were determined after 48 h of
      culture. RESULTS: The respective values for leptin in follicular fluid from
      small, medium and large follicles were 1.98, 2.18 and 1.96 ng/ml, respectively.
      Leptin added alone at a dose of 2 ng/ml had no effect on basal steroid secretion
      by small and medium follicles. However, in small follicles a synergic action of
      GH and IGF-I was noted. Leptin did not influence the secretion of progesterone by
      follicles collected during the early and middle follicular phases. In
      preovulatory follicles, leptin added alone to the culture media caused a decrease
      in basal estradiol secretion with a concomitant increase in progesterone
      secretion. Moreover, it acted synergistically with IGF-I and GH causing further
      stimulation of progesterone secretion. CONCLUSIONS: The presented data show a
      direct, maturation dependent action of leptin on GH and IGF-I stimulated
      follicular steroidogenesis. During follicular growth they acted synergistically
      with GH and IGF-I in estradiol production, while in preovulatory follicles, they
      acted with both investigated hormones in luteinization process, which starts
      before follicular disruption.

PMID- 15147235
TI  - Effect of excitatory amino acids on activity of vasopressinergic and
      oxytocinergic neurons.
AB  - A few compounds function as the excitatory amino acid (EAA) transmitters in the
      central nervous system (CNS), but glutamate (Glu) is the most important. Data on
      Glu participation in the control of vasopressinergic (AVP-ergic) and
      oxytocinergic (OXT-ergic) neuronal activity have been collected mainly on the
      basis of observations of hypothalamic AVP-ergic and OXT-ergic neurons. In vivo
      and in vitro experiments have demonstrated that Glu enhances bioelectric activity
      of the aforementioned neurons and increases AVP and OXT release. However,
      inhibitory effect of Glu on AVP-ergic neurons, mediated by local GABA-ergic
      interneurons, is also possible. Both ionotropic and metabotropic receptors
      participate in EAA effect on AVP-ergic and OXT-ergic neurons. EAA involvement in
      AVP and OXT release after osmotic stimuli and in OXT release during the milk
      ejection reflex has been demonstrated. Recent findings demonstrated that EAA
      enhanced AVP release into the extracellular fluid of hippocampus in the rabbit.

PMID- 15147236
TI  - 1alpha,25-dihydroxyvitamin D3 inducible transcription factor and its role in the
      vitamin D action.
AB  - Vitamin D is considered multifunctional steroid hormone that modulates calcium
      homeostasis through actions predominantly in kidney, bone and the intestinal
      tract. Nuclear vitamin D receptor (VDR) is a specific nuclear protein, a member
      of steroid hormone receptor superfamily. The amino acid sequence of the VDR shows
      a significant homology with other members of the nuclear hormone receptor
      superfamily, including receptors for glucocorticoids (GR), oestrogen (ER),
      androgen (AR), progesteron (PR), thyroid hormone (T3R), retinoic acid (RAR),
      retinoid X (RXR) and over 150 orphan receptors. VDR is known to mediate the
      pleiotropic biological actions of 1a,25-dihydroxyvitamin D3 through its ability
      to modulate the expression of target genes. VDR upon binding 1a,25
      dihydroxyvitamin D3 regulates specific gene transcription predominantly by
      binding as a heterodimer with the retinoid X receptor (RXR) to DNA enhancer
      sequence, termed the vitamin D-responsive element (VDRE) that is present within
      the promoter region of vitamin D-controlled genes. The VDR has been shown to
      associate with several additional molecules to form the active transcriptional
      complex required for gene regulation. The regulation of this ligand-activated
      cellular transcription factor occurs at both transcriptional and
      posttranslational levels. This article summarizes a variety of effects of 1a,25
      dihydroxyvitamin D3, acting through its cognate nuclear receptor, and its use in
      chemotherapy and chemoprevention of cancer.

PMID- 15147237
TI  - Molecular modelling of the nucleotide-binding domain of Wilson's disease protein:
      location of the ATP-binding site, domain dynamics and potential effects of the
      major disease mutations.
AB  - WNDP (Wilson's disease protein) is a copper-transporting ATPase that plays an
      essential role in human physiology. Mutations in WNDP result in copper
      accumulation in tissues and cause a severe hepato-neurological disorder known as
      Wilson's disease. Several mutations were surmised to affect the nucleotide
      binding and hydrolysis by WNDP; however, how the nucleotides bind to normal and
      mutated WNDP remains unknown. To aid such studies, we performed the molecular
      modelling of the spatial structure and dynamics of the ATP-binding domain of WNDP
      and its interactions with ATP. The three-dimensional models of this domain in two
      conformations were built using the X-ray structures of the Ca2+-ATPase in the E1
      and E2 states. To study the functional aspects of the models, they were subjected
      to long-term molecular dynamics simulations in an explicit solvent; similar
      calculations were performed for the ATP-binding domain of Ca2+-ATPase. In both
      cases, we found large-scale motions that lead to significant changes of distances
      between several functionally important residues. The ATP docking revealed two
      possible modes of ATP binding: via adenosine buried in the cleft near residues
      H1069, R1151 and D1164, and via phosphate moiety 'anchored' by H-bonds with
      residues in the vicinity of catalytic D1027. Furthermore, interaction of ATP with
      both sites occurs if they are spatially close to each other. This may be achieved
      after relative domain motions of the 'closure' type observed in molecular
      dynamics simulations. The results provide a framework for analysis of disease
      mutations and for future mutagenesis studies.

PMID- 15147238
TI  - Membrane lipid biosynthesis in Chlamydomonas reinhardtii: expression and
      characterization of CTP:phosphoethanolamine cytidylyltransferase.
AB  - CTP:phosphoethanolamine cytidylyltransferase (ECT) is considered to be the
      regulatory enzyme in the CDP-ethanolamine pathway of phosphatidylethanolamine
      (PE) biosynthesis. The ECT cDNA of Chlamydomonas reinhardtii encodes a protein of
      443 amino acid residues, which is longer than the same protein in yeast, rat or
      human. The translated product of cloned cDNA was expressed as a fusion protein in
      Escherichia coli, and was shown to have ECT activity. The deduced amino acid
      sequence has 41% identity with that of human or rat, and 30% with yeast. The ECT
      protein has a repetitive internal sequence in its N- and C-terminal halves and a
      signature peptide sequence, RTXGVSTT, typical of the cytidylyltransferase family.
      The first 70 amino acid residues do not match the N-terminal part of the
      cytidylyltransferases from other organisms, and we hypothesize that it is a
      subcellular targeting signal to mitochondria. ECT and organelle marker enzyme
      assays showed that the total activity of ECT correlates well with that of
      fumarase, a marker enzyme for mitochondria. Northern blots showed an increase in
      mRNA abundance during reflagellation, indicating a possibility of transcriptional
      regulation. A notable change in the enzyme activity in C. reinhardtii cells was
      observed during the cell cycle, increasing during the dark and then decreasing
      during the light period, while the mRNA level did not alter, providing evidence
      for post-translational regulation.

PMID- 15147239
TI  - Characterization of bromosulphophthalein binding to human glutathione S
      transferase A1-1: thermodynamics and inhibition kinetics.
AB  - In addition to their catalytic functions, GSTs (glutathione S-transferases) bind
      a wide variety of structurally diverse non-substrate ligands. This ligandin
      function is known to result in the inhibition of catalytic function. The
      interaction between hGSTA1-1 (human class Alpha GST with two type 1 subunits) and
      a non-substrate anionic ligand, BSP (bromosulphophthalein), was studied by
      isothermal titration calorimetry and inhibition kinetics. The binding isotherm is
      biphasic, best described by a set of two independent sites: a high-affinity site
      and a low-affinity site(s). The binding stoichiometries for these sites are 1 and
      3 molecules of BSP respectively. BSP binds to the high-affinity site 80 times
      more tightly (K(d)=0.12 microM) than it does to the low-affinity site(s)
      (K(d)=9.1 microM). Binding at these sites is enthalpically and entropically
      favourable, with no linkage to protonation events. Temperature- and salt
      dependent studies indicate the significance of hydrophobic interactions in the
      binding of BSP, and that the low-affinity site(s) displays low specificity
      towards the anion. Binding of BSP results in the release of ordered water
      molecules at these hydrophobic sites, which more than offsets unfavourable
      entropic changes during binding. BSP inhibition studies show that the binding of
      BSP to its high-affinity site does not inhibit hGSTA1-1. This site, located near
      Trp-20, may be related to the buffer-binding site observed in GSTP1-1. The low
      affinity-binding site(s) for BSP is most probably located at or near the active
      site of hGSTA1-1. Binding to this site(s) results in non-competitive inhibition
      with respect to CDNB (1-chloro-2,4-dinitrobenzene) (K(i)(BSP)=16.8+/-1.9 microM).
      Given the properties of the H site and the relatively small size of the
      electrophilic substrate CDNB, it is plausible that the active site of the enzyme
      can simultaneously accommodate both BSP and CDNB. This would explain the non
      competitive behaviour of certain inhibitors that bind the active site (e.g. BSP).

PMID- 15147240
TI  - Topology of the substrate-binding site of a Lys49-phospholipase A2 influences
      Ca2+-independent membrane-damaging activity.
AB  - BthTx-I (bothropstoxin-I) is a myotoxic Lys49-PLA2 (phospholipase A2 with Lys49)
      isolated from Bothrops jararacussu venom, which damages liposome membranes by a
      Ca2+-independent mechanism. The highly conserved Phe5/Ala102/Phe106 motif in the
      hydrophobic substrate-binding site of the Asp49-PLA2s is substituted by
      Leu5/Val102/Leu106 in the Lys49-PLA2s. The Leu5/Val102/Leu106 triad in BthTx-I
      was sequentially mutated via all single- and double-mutant combinations to the
      Phe5/Ala102/Phe106 mutant. All mutants were expressed as inclusion bodies in
      Escherichia coli, and the thermal stability (Tm), together with the myotoxic and
      Ca2+-independent membrane-damaging activities of the recombinant proteins, were
      evaluated. The far-UV CD profiles of the native, wild-type recombinant and the
      L106F (Leu106-->Phe) and L5F/F102A/L106F mutant proteins were identical. The L5F,
      V102A, L5F/V102A and V102A/L106F mutants showed distorted far-UV CD profiles;
      however, only the L5F and L5F/V102A mutants showed significant decreases in Tm.
      Alterations in the far-UV CD spectra correlated with decreased myotoxicity and
      protein-induced release of a liposome-entrapped marker. However, the V102A/L106F
      and L5F/V102A/L106F mutants, which presented high myotoxic activities, showed
      significantly reduced membrane-damaging activity. This demonstrates that the
      topology of the substrate-binding region of BthTx-I has a direct effect on the
      Ca2+-independent membrane damage, and implies that substrate binding retains an
      important role in this process.

PMID- 15147245
TI  - Tools for diagnosing migraine and measuring its severity.
AB  - Migraine remains substantially underdiagnosed and undertreated in the United
      States. Tools to screen for migraine and to measure headache-related disability
      can help address barriers to effective diagnosis and treatment. In this article,
      public health criteria for screening programs for any medical condition are first
      reviewed. Modifications of these criteria for migraine and other chronic/episodic
      disorders are then proposed. Migraine is assessed to determine how well it meets
      criteria for screening and the steps that are necessary before firm public policy
      recommendations for screening for migraine are possible.

PMID- 15147241
TI  - Chondroitin sulphate structure affects its immunological activities on murine
      splenocytes sensitized with ovalbumin.
AB  - Chondroitin sulphate (CS) is a glycosaminoglycan widely distributed in animal
      tissues, which has anti-inflammatory and chondroprotective properties. We
      reported previously that chondroitin 4-sulphate (CS-A) up-regulates the antigen
      specific Th1 immune response of murine splenocytes sensitized with ovalbumin in
      vitro, and that CS suppresses the antigen-specific IgE responses. We now
      demonstrate that a specific sulphation pattern of the CS polysaccharide is
      required for the Th1-promoted activity, as other polysaccharides such as dextran
      and dextran sulphate do not significantly induce this activity. While the
      presence of some O-sulpho groups appear to be essential for activity, CS-A, and
      synthetically prepared, partially O-sulphonated CS, induce higher Th1-promoted
      activity than synthetically prepared, fully O-sulphonated CS. CS-A induces an
      activity greater than chondroitin sulphate B (CS-B) or chondroitin 6-sulphate (CS
      C). In addition, chondroitin sulphate E (CS-E) induces greater activity than CS-A
      or CS-D. These results suggest that the GlcA(beta1-3)GalNAc(4,6-O-disulpho)
      sequence in CS-E is important for Th1-promoted activity. Furthermore, rat anti
      mouse CD62L antibody, an antibody to L-selectin, inhibits the Th1-promoting
      activity of CS. These results suggest that the Th1-promoted activity could be
      associated with L-selectin on lymphocytes. These findings describe a new
      mechanism for the anti-inflammatory and chondroprotective properties of CS that
      may be useful in designing new therapeutic applications for CS used in the
      treatment of immediate-type hypersensitivity.

PMID- 15147246
TI  - A thromboembolic predisposition and the effect of anticoagulants on migraine.
AB  - OBJECTIVE: To investigate the presence of thromboembolic risk factors and the
      effect of low-dose acenocoumarol therapy on migraine in patients who
      spontaneously reported a reduction of their migraine attacks during previous
      therapeutic use of anticoagulants. BACKGROUND: The positive effect of
      anticoagulants on migraine has been described in case reports and observational
      studies. It remains unclear whether this concerns only a select group of
      migraineurs with certain common characteristics. METHODS: In 4 migraineurs with a
      self-reported reduction of attack frequency during previous use of anticoagulants
      (international normalization ratio [INR], 2.5:4.0), the presence of
      thromboembolic risk factors and the effect of low-dose acenocoumarol therapy
      (INR, 1.5:2.0) on migraine attacks were prospectively investigated in an open
      study. RESULTS: All patients had one or more thromboembolic risk factors. Two
      patients, both with factor V Leiden heterozygosity, experienced a clear
      improvement of migraine during low-dose acenocoumarol therapy. CONCLUSIONS: Our
      findings support the hypothesis that migraine, as a phenotype, has different
      underlying mechanisms, amongst which a thromboembolic tendency. In this group of
      patients, oral anticoagulants may be a suitable form of migraine prophylaxis, but
      this needs further clinical investigation.

PMID- 15147247
TI  - Frovatriptan use in migraineurs with or at high risk of coronary artery disease.
AB  - OBJECTIVE: To investigate the cardiovascular effects of frovatriptan 2.5 mg
      during a migraine attack in patients with, or at high risk of, coronary artery
      disease. BACKGROUND: Rare occurrences of myocardial ischemia and coronary and
      peripheral vasospasm associated with the use of sumatriptan have triggered
      concern over the vasoconstrictor properties of the triptan class of drugs.
      METHODS: This randomized, double-blind, placebo-controlled, parallel-group study
      was conducted in 14 US private headache referral centers or clinics. Seventy-five
      patients, aged 18 years and older, with a history of migraine who were at high
      risk (Framingham score > or =14) of or who had previously documented coronary
      artery disease were evaluated. RESULTS: Incidence of clinically significant
      electrocardiogram changes was higher at all time points postdose with placebo
      than with frovatriptan, reaching statistical significance at 4 hours (40% versus
      19%, P=.026). Similar proportions of patients had ischemia documented on Holter
      monitoring in the placebo (13%) and frovatriptan (11%) groups, and the incidence
      of arrhythmias was higher in the placebo group (11% versus 3%). There were no
      clinically significant changes in heart rate or blood pressure in either group.
      Adverse event profiles were similar for placebo and frovatriptan. CONCLUSIONS: In
      this exploratory study of migraineurs with, or at high risk of, coronary artery
      disease, frovatriptan 2.5 mg was well tolerated and not associated with an
      increase in cardiovascular monitoring abnormalities.

PMID- 15147242
TI  - Expression of the gene for Dec2, a basic helix-loop-helix transcription factor,
      is regulated by a molecular clock system.
AB  - Dec2, a member of the basic helix-loop-helix superfamily, is a recently confirmed
      regulatory protein for the clockwork system. Transcripts of Dec2, as well as
      those of its related gene Dec1, exhibit a striking circadian oscillation in the
      suprachiasmatic nucleus, and Dec2 inhibits transcription from the Per1 promoter
      induced by Clock/Bmal1 [Honma, Kawamoto, Takagi, Fujimoto, Sato, Noshiro, Kato
      and Honma (2002) Nature (London) 419, 841-844]. It is known that mammalian
      circadian rhythms are controlled by molecular clockwork systems based on negative
      feedback loop(s), but the molecular mechanisms for the circadian regulation of
      Dec2 gene expression have not been clarified. We show here that transcription of
      the Dec2 gene is regulated by several clock molecules and a negative-feedback
      loop. Luciferase and gel retardation assays showed that expression of Dec2 was
      negatively regulated by binding of Dec2 or Dec1 to two CACGTG E-boxes in the Dec2
      promoter. Forced expression of Clock/Bmal1 and Clock/Bmal2 markedly increased
      Dec2 mRNA levels, and up-regulated the transcription of the Dec2 gene through the
      CACGTG E-boxes. Like Dec, Cry and Per also suppressed Clock/Bmal-induced
      transcription from the Dec2 promoter. Moreover, the circadian expression of Dec2
      transcripts was abolished in the kidney of Clock/Clock mutant mice. These
      findings suggest that the Clock/Bmal heterodimer enhances Dec2 transcription via
      the CACGTG E-boxes, whereas the induced transcription is suppressed by Dec2,
      which therefore must contribute to its own rhythmic expression. In addition, Cry
      and Per may also modulate Dec2 transcription.

PMID- 15147248
TI  - Ponytail headache: a pure extracranial headache.
AB  - Fifty of 93 females experienced headache from wearing a ponytail. Pain was
      experienced only at the site of the hair tie in 10 subjects, extending in others,
      forwards to the vertex (n = 5) or forehead (n = 7), laterally to the parietal
      region (n = 8) or temples (n = 3), downwards to the neck (n = 5), or to other
      areas (n = 12). Loosening the hair relieved pain immediately in 4 subjects,
      within half an hour in 32, and within an hour in 5 subjects; the remaining 9
      subjects were uncertain of pain duration. This headache was preventable by
      wearing the ponytail more loosely tied. Ponytail headache, well known to females,
      is not described in the medical literature because the remedy is obvious,
      therefore those affected do not seek medical advice. This seemingly common
      headache provides an example of a pure extracranial headache arising from
      pericranial muscle fascia and tendon traction. Males almost certainly have
      similar experiences, but were not questioned in this study. Distinguishing
      intracranial from extracranial headache is essential in diagnosis and treatment.
      Further research on ponytail and other extracranial headaches could shed light on
      the mechanism of tension-type headache.

PMID- 15147249
TI  - Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in
      the acute treatment of migraine.
AB  - BACKGROUND: Health care providers frequently cite concerns about cardiovascular
      safety of the triptans as a barrier to their use. In 2002, the American Headache
      Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the
      evidence on triptan-associated cardiovascular risk and to formulate consensus
      recommendations for making informed decisions for their use in patients with
      migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan
      Cardiovascular Safety Expert Panel and their recommendations for the use of
      triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety
      Expert Panel was composed of a multidisciplinary group of experts in neurology,
      primary care, cardiology, pharmacology, women's health, and epidemiology.
      EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published
      literature was reviewed by each panel member in preparation for an open
      roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of
      triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment,
      migraine) were presented as a prelude to group discussion and formulation of
      consensus conclusions and recommendations. Follow-up meetings were held by
      telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from
      patients without known coronary artery disease. (2) Chest symptoms occurring
      during use of triptans are generally nonserious and are not explained by
      ischemia. (3) The incidence of serious cardiovascular events with triptans in
      both clinical trials and clinical practice appears to be extremely low. (4) The
      cardiovascular risk-benefit profile of triptans favors their use in the absence
      of contraindications.

PMID- 15147250
TI  - Understanding the patient with migraine: the evolution from episodic headache to
      chronic neurologic disease. A proposed classification of patients with headache.
AB  - Traditionally, episodic primary headache disorders are characterized by a return
      of preheadache (normal) neurologic function between episodes of headache. In
      contrast, patients with chronic headache often do not return to normal neurologic
      function between headache attacks. This article proposes that the evolution from
      episodic migraine to chronic headache may parallel the neurologic disruption
      observed during the progression of an acute migraine attack and that changes in
      baseline neurologic function between episodes of headache may be a more sensitive
      indicator of headache transformation than headache frequency alone. Early
      recognition of nonheadache changes in nervous system function may offer a more
      sensitive and specific approach to migraine prevention.

PMID- 15147251
TI  - Topiramate-responsive headache due to idiopathic intracranial hypertension in
      Behcet syndrome.
AB  - A 14-year-old adolescent was seen with an 8-month history of almost daily
      incapacitating headaches due to idiopathic intracranial hypertension in Behcet
      syndrome. All his clinical signs and symptoms, including headache, resolved 2 to
      4 weeks after topiramate was initiated. An effect on carbonic anhydrase
      isoenzymes II and IV, reducing cerebrospinal fluid production, could potentially
      explain the beneficial effect of topiramate in intracranial hypertension. Further
      studies are necessary, however, to confirm the significance of topiramate in this
      indication.

PMID- 15147252
TI  - An unusual case of an airplane headache.
AB  - A 28-year-old man developed severe headache associated with changes in altitude
      during ascent and descent while flying in an airplane. Jabbing pain over the
      forehead and between the eyes began within minutes of ascent. It resolved once a
      cruising altitude was reached, but then returned at the start of descent.

PMID- 15147254
TI  - Headache as an initial symptom of basilar artery thrombosis.

PMID- 15147253
TI  - Venous angioma associated with atypical ophthalmoplegic migraine.
AB  - BACKGROUND: Ophthalmoplegic migraine is a rare syndrome in which episodic
      headaches are associated with ophthalmoplegia. Several recent reports emphasize
      the possibility, especially in atypical cases, of a heterogeneous type of
      ophthalmoplegic migraine. METHODS: We describe the case of an 18-year-old woman
      with recurrent episodic headache accompanied by binocular diplopia due to left
      third cranial nerve palsy. The symptoms resolve in hours. A diagnosis of atypical
      ophthalmoplegic migraine was established. RESULTS: Digital angiography revealed a
      venous angioma draining into the left cavernous sinus. CONCLUSIONS: This case
      reveals the importance of differential diagnosis in atypical migraine in which
      the symptomatology could be secondary to intracranial lesions. We propose venous
      stasis as a cause of symptoms.

PMID- 15147255
TI  - Seroprevalence of chronic infections in migraine.

PMID- 15147256
TI  - Magnesium therapy for migraine: do we need more trials or more reflection?

PMID- 15147257
TI  - Metoclopramide and sumatriptan.

PMID- 15147258
TI  - Limb pain and peripheral and central sensitization.

PMID- 15147268
TI  - Molecular interactions of fission yeast Skp1 and its role in the DNA damage
      checkpoint.
AB  - Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box).
      It forms an adapter bridge between Cullin-1 and the substrate-determining
      component, the F-box protein. In order to establish the role of Skp1, a
      temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase
      chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated
      residues on the 3-D structure of human Skp1 suggested that the mutants would be
      compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to
      assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope
      tagged, and co-immunoprecipitation performed. This systematic analysis showed
      that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box
      proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and
      nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay,
      which is attributable to activation of the DNA damage checkpoint. Intriguingly,
      contrary to pof3 mutants, in which this checkpoint is required for survival,
      checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost
      rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint
      therefore differs between pof3Delta and skp1(ts), implicating a novel role for
      Skp1 in the checkpoint-signalling cascade.

PMID- 15147269
TI  - The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase.
AB  - Human Lats2, a novel serine/threonine kinase, is a member of the Lats kinase
      family that includes the Drosophila tumour suppressor lats/warts. Lats1, a
      counterpart of Lats2, is phosphorylated in mitosis and localized to the mitotic
      apparatus. However, the regulation, function and intracellular distribution of
      Lats2 remain unclear. Here, we show that Lats2 is a novel phosphorylation target
      of Aurora-A kinase. We first showed that the phosphorylated residue of Lats2 is
      S83 in vitro. Antibody that recognizes this phosphorylated S83 indicated that the
      phosphorylation also occurs in vivo. We found that Lats2 transiently interacts
      with Aurora-A, and that Lats2 and Aurora-A co-localize at the centrosomes during
      the cell cycle. Furthermore, we showed that the inhibition of Aurora-A-induced
      phosphorylation of S83 on Lats2 partially perturbed its centrosomal localization.
      On the basis of these observations, we conclude that S83 of Lats2 is a
      phosphorylation target of Aurora-A and this phosphorylation plays a role of the
      centrosomal localization of Lats2.

PMID- 15147270
TI  - The C-terminus of Bfa1p in budding yeast is essential to induce mitotic arrest in
      response to diverse checkpoint-activating signals.
AB  - During mitosis, genomic integrity is maintained by the proper coordination of
      anaphase entry and mitotic exit through mitotic checkpoints. In budding yeast,
      exit from mitosis is triggered by the activation of the small GTPase Tem1p. Bfa1p
      in association with Bub2p negatively regulates Tem1p in response to spindle
      damage, spindle misorientation, and DNA damage, resulting in cell cycle arrest.
      To delineate the Bfa1p domains that respond to distinct checkpoint signals, we
      constructed 13 Bfa1 deletion mutants. The C-terminal 184 amino acids of Bfa1p
      (Bfa1-D8(391-574)) contained the entire capacity of Bfa1p to generate mitotic
      arrest in response to spindle damage, spindle misorientation, and DNA damage.
      This domain was also enough to interact with the mitotic exit network proteins
      Tem1p, Bub2p, and Cdc5p, and to localize to the spindle pole body (SPB). Over
      expression of Bfa1-D8(391-574) induced late anaphase arrest as efficient as the
      full-length Bfa1p in a Bub2p-dependent manner. In contrast, the N-terminal
      portion of Bfa1p (Bfa1-D16(1-376)) could not localize to SPB and did not block
      mitotic exit in response to diverse checkpoint signals. Bfa1-D16(1-376)
      interacted with Tem1p but not with Bub2p and its over-expression partially
      arrested cells in mitosis in the absence of Bub2p. By random mutagenesis of Bfa1
      D8(391-574) with hydroxylamine, we isolated a point mutant of D8, D8(E438K),
      which interacts with both Tem1p and Bub2p but cannot respond to checkpoint
      signals. This mutant also showed reduced efficiency in the localization to SPB.
      Taken together, our study demonstrated that various checkpoint signals are
      transmitted to the C-terminal domain of Bfa1 (Bfa1-D8(391-574)) and that Bfa1p
      localization to SPB is necessary but not sufficient to regulate mitotic exit in
      response to various checkpoint signals.

PMID- 15147271
TI  - Transcriptional co-activator activity of SYT is negatively regulated by BRM and
      Brg1.
AB  - The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the
      fusion of the SYT gene on chromosome 18 to the SSX gene on chromosome X. Although
      the SYT-SSX fusion proteins may trigger synovial sarcoma development, the
      biological functions of SYT, SSX and SYT-SSX genes are unclear. Transfections of
      Gal4 DNA binding domain fusion protein constructs demonstrate that SYT protein
      acts as a transcriptional co-activator at the C-terminal domain and that the
      activity is repressed through the N-terminus. The N-terminal 70 amino acids of
      SYT bind not only to BRM, but also to Brg1, both of which are subunits of SWI/SNF
      chromatin remodelling complexes. Here, we have investigated the functions of BRM
      and Brg1 on the repression of SYT activity. The negative regulation of SYT
      transcriptional co-activator activity is dependent on the ATP-hydrolysis of BRM
      and Brg1 in the protein complexes. This indicates that the SWI/SNF protein
      complexes regulate SYT activity using the chromatin remodelling activity.

PMID- 15147272
TI  - Heat-shock induced nuclear retention and recycling inhibition of importin alpha.
AB  - Heat-shock induces a strong stress response and modifies all aspects of cellular
      physiology, which involves dynamic changes in the nucleocytoplasmic distributions
      of a variety of proteins. Many distinct nucleocytoplasmic transport pathways
      exist in eukaryotic cells, but how a particular transport pathway is regulated
      under different cellular conditions remains elusive. The finding of this study
      indicate that conventional nuclear import, which is mediated by importin
      alpha/beta, is down-regulated, while the nuclear import of 70 kD heat-shock
      cognate protein is up-regulated in heat-shock cells. Among the factors involved
      in the mediation of the conventional nuclear import, significant levels of
      importin alpha accumulate in the nucleus in response to heat-shock. An analysis
      of the behaviour of importin alpha with fluorescence recovery after
      photobleaching and fluorescence loss in photobleaching studies show that nuclear
      importin alpha becomes less mobile and its nucleocytoplasmic recycling is
      impaired in heat-shock cells. These data coincided well with biochemical and
      cytological studies. Our present data show that heat-shock induces the nuclear
      accumulation, nuclear retention, and recycling inhibition of importin alpha,
      resulting in the suppression of conventional nuclear import. This suggests a new
      regulatory mechanism for the adaptation of cells to environmental changes, such
      as heat-shock.

PMID- 15147273
TI  - A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox,
      the regulatory subunit of the phagocyte NADPH oxidase.
AB  - The phagocyte NADPH oxidase is a multisubunit enzyme responsible for the
      production of reactive oxygen species. p47(phox) is a cytosolic component of the
      NADPH oxidase and plays an important role in the assembly of the activated
      complex. The structural determination of the tandem SH3 domains of p47(phox) is
      crucial for elucidation of the molecular mechanism of the activation of
      p47(phox). We determined the X-ray crystal structure of the tandem SH3 domains
      with the polybasic/autoinhibitory region (PBR/AIR) of p47(phox). The GAPPR
      sequence involved in PBR/AIR forms a left-handed polyproline type-II helix (PPII)
      and interacts with the conserved SH3 binding surfaces of the SH3 domains
      simultaneously. These SH3 domains are related by a 2-fold pseudosymmetry axis at
      the centre of the binding groove and interact with the single PPII helix formed
      by the GAPPR sequence with opposite orientation. In addition, a number of intra
      molecular interactions among the SH3 domains, PBR/AIR and the linker tightly hold
      the architecture of the tandem SH3 domains into the compact structure and
      stabilize the autoinhibited form synergistically. Phosphorylation of the serine
      residues in PBR/AIR could destabilize and successively release the intra
      molecular interactions. Thus, the overall structure could be rearranged from the
      autoinhibitory conformation to the active conformation and the PPII ligand
      binding surfaces on the SH3 domains are now unmasked, which enables their
      interaction with the target sequence in p22(phox).

PMID- 15147274
TI  - Role of Herp in the endoplasmic reticulum stress response.
AB  - Application of differential display to cultured rat astrocytes allowed cloning of
      Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER)
      stress, it decayed rapidly consequent to proteasome-mediated degradation. To
      investigate the role of this molecule in terms of the stress response, Herp
      knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null
      cells were more vulnerable to ER stress compared with F9 wild-type cells. In the
      early period of ER stress (0-8 h after tunicamycin treatment), Herp null cells
      displayed enhanced ER stress signalling and stabilization of an endogenous ERAD
      substrate, compared with wild-type cells. In the intermediate period (8-20 h
      after tunicamycin treatment), Herp null cells displayed reduced ER stress
      signalling, whereas in the late period (20-40 h after tunicamycin treatment),
      Herp null cells manifested irreversible cellular changes that lead to apoptotic
      cell death. Transfection analysis revealed that the N-terminal region, including
      the ubiquitin-like domain of Herp, was required for the survival of F9 cells
      under ER stress. These results indicate that Herp is a short-lived Ub-like
      protein improving the balance of folding capacity and protein loads in the ER and
      plays crucial roles for the ER stress resistance in F9 cells.

PMID- 15147275
TI  - A novel mechanism for regulating clonal propagation of mouse ES cells.
AB  - Self-renewal and differentiation of embryonic stem (ES) cells are controlled by
      the combinatorial action of extracellular signals and regulation of gene
      expression. For characterizing the entire molecular mechanism governing these
      events, we first established a feeder- and serum-free culture system in which
      mouse ES cells could propagate in clonal density in keeping with proper
      pluripotency. Supplementation of peptide hormones such as adrenocorticotropic
      hormone (ACTH) is required to remove serum, and the key event in this phenomenon
      may be the inhibition of the adenylyl cyclase (AC) activity, as it replaces the
      effect of these peptides. Because ES cells themselves produce the same activity,
      the finding suggests a novel mechanism in which activation of AC restricts clonal
      propagation of pluripotent stem cells.

PMID- 15147276
TI  - Identification of cryptochrome DASH from vertebrates.
AB  - A new type of cryptochrome, CRY-DASH, has been recently identified. The CRY-DASH
      proteins constitute the fifth subfamily of the photolyase/cryptochrome family.
      CRY-DASHs have been identified from Synechocystis sp. PCC 6803, Vibrio cholerae,
      and Arabidopsis thaliana. The Synechocystis CRY-DASH was the first cryptochrome
      identified from bacteria, and its biochemical features and tertiary structure
      have been extensively investigated. To determine how broadly the subfamily is
      distributed within living organisms, we searched for new CRY-DASH candidates
      within several databases. We found five sequences as new CRY-DASH candidates,
      which are derived from four marine bacteria and Neurospora crassa. We also found
      many CRY-DASH candidates from the EST databases, which included sequences from
      fish and amphibians. We cloned and sequenced the cDNAs of the zebrafish and
      Xenopus laevis candidates, based on the EST sequences. The proteins encoded by
      the two genes were purified and characterized. Both proteins contained folate and
      flavin cofactors, and have a weak DNA photolyase activity. A phylogenetic
      analysis revealed that the seven candidates actually belong to the new type of
      cryptochrome subfamily. This is the first report of the CRY-DASH members from
      vertebrates and fungi.

PMID- 15147278
TI  - Pharmacoeconomics of adverse drug reactions.
AB  - Abstract Adverse drug reactions (ADRs) are common causes of hospitalization and
      lead to large costs to society. The cost of hospitalization is, however, only a
      part of the total costs as most adverse reactions never come to clinical
      attention. There are two main costs associated with ADRs, cost of treating
      illnesses due to ADRs and cost of avoiding them. The main objective of this study
      was to discuss the social costs of ADRs from an economic point of view. We also
      reviewed the literature and summarized studies investigating cost and occurrence
      of adverse reactions. Three different approaches to assess the costs of ADR are
      distinguished. The first is cost studies, where the following three steps must be
      done to estimate the costs: define ADR, estimated the incidence of ADRs and
      measure the costs of ADRs. Most cost studies have focused on hospitalizations due
      to ADRs and the literature shows that about 3-7% of all hospitalizations are
      caused by ADRs. The second approach concerns costs and benefits of safety: the
      decision to prescribe, use, distribute or produce a drug involves both costs and
      benefits, and decisions makers must weigh costs of ADRs against costs of avoiding
      them. The third approach discusses regulations and mechanisms for achieving an
      optimal balance between costs and benefits of drug therapies. The problem with
      ADRs is, from an economic point of view, not a problem of minimization but of
      optimization, to find the right balance between costs and benefits.

PMID- 15147279
TI  - Is it important to correct apparent drug tissue concentrations for blood
      contamination in the dog?
AB  - The goal of this study was to quantify in the dog the error that is made in
      assessing drug tissue concentrations when no correction for blood contamination
      is performed and hence to determine in which organs such a correction should be
      made. The organs investigated were the heart, the brain, the liver and the
      skeletal muscle, and the test drug used was the H1-antihistamine, cetirizine (0.1
      or 0.6 mg/kg/day for 3 days, orally, n = 6 dogs). Radiolabelled serum albumin was
      used to quantitate blood trapped in the tissues. Blood and tissue samplings were
      performed 2 h after the last drug administration. Mean (+/-SEM) volumes of blood
      trapped in the liver, heart, muscle and brain were 263 +/- 12, 91 +/- 3, 27 +/- 1
      and 20 +/- 2 microL/g, respectively. Apparent tissue/blood concentration ratios
      of cetirizine were 2.39 +/- 0.33, 1.11 +/- 0.09, 0.77 +/- 0.07 and 0.37 +/- 0.05
      in the four organs. When correction for residual blood is not performed,
      cetirizine concentrations are underestimated (-13.6 +/- 3.2%) in the liver,
      slightly overestimated (+4.7 +/- 1.5 to +6.3 +/- 2.8%) in the brain, and neither
      over nor underestimated in the heart and muscle. Simulation data over a wide
      range of theoretical drug tissue/blood concentration ratios indicate that in the
      dog: (a) for the liver, correction of apparent tissue concentration for residual
      blood should be performed when the drug tissue/blood concentration ratio achieved
      is <0.8 or >4, (b) for the heart, correction should be made when this ratio is <
      or =0.4 and (c) for the brain and muscle, no correction is necessary unless the
      ratio is < or =0.1.

PMID- 15147280
TI  - Physiological and metabolic actions of mycophenolate mofetil on cultured newborn
      rat cardiomyocytes in normoxia and in simulated ischemia.
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute
      rejection after heart transplantation. As with other immunosuppressive drugs, MMF
      therapy is associated with several adverse effects. However, the direct effects
      of MMF on myocardial tissue has not been yet evaluated. The aim of the work was
      thus to evaluate the effects of MMF on isolated cardiomyocytes (CM) in normal
      conditions and in an in vitro model of simulated ischemia (SI; substrate-free
      hypoxia) and reperfusion (R; reoxygenation). Myocyte-enriched cultures were
      prepared from newborn rat heart ventricles. The transmembrane potentials were
      recorded using conventional microelectrodes and the cell contractions were
      monitored with a photoelectric device. In basal conditions, MMF (10(-6) and 10(
      5) M) exerted no significant effects on the survival and on the electrical and
      contractile activities of CM in culture, even during long-term exposure (up to 48
      h). SI per se led to a gradual decrease and then an abortion of the spontaneous
      automaticity and electromechanical activity of CM. Pretreating CM with either 10(
      6) or 10(-5) M MMF was able to reduce the SI-induced cell dysfunctions. The
      presence of MMF at these concentrations did not hamper the post-SI functional
      recovery of CM during reoxygenation. At 10(-5) M, MMF applied during
      reoxygenation only permitted a better recovery of CM. However, the mitochondrial
      function after reoxygenation, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide (MTT) test, was not significantly influenced by the
      addition of MMF before as well as after ischemia. Conversely, MMF was able to
      reduce in this model the postischemic rise in xanthine and hypoxanthine. These
      data from CM-enriched model show that MMF: (i) had no cytotoxic effect, (ii)
      displayed a cytoprotective effect during SI, and (iii) exerted its beneficial
      effect at least partly through the decrease in the xanthine oxidase-dependent
      free radical production.

PMID- 15147281
TI  - Effects of differential blockade of the renin-angiotensin system in postinfarcted
      rats.
AB  - The present study compared short-term effects of the AT(1)-receptor antagonist,
      irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on
      systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI)
      rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50
      mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics
      were measured. Compared with the sham-operated group, left ventricular end
      diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body
      weight ratio were all significantly increased in the MI group while the LV
      contractility (dP/dt) and pulsatile arterial pressure were significantly reduced.
      Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy.
      Furthermore, irbesartan attenuated the right shift of the pressure-volume curves,
      prevented postinfarction-induced increase in urinary cyclic guanosine
      monophosphate and reduced urinary aldosterone excretion. Although both drugs were
      able to prevent further cardiac hypertrophy and improved cardiac filling
      pressure, only irbesartan limited LV dilatation. These data indicate that
      blockade of the renin-angiotensin system at the level of AT1 receptors may have a
      better cardioprotective benefit than reducing angiotensin II levels by ACE
      inhibition.

PMID- 15147282
TI  - The evaluation of the N-type channel blocking properties of cilnidipine and other
      voltage-dependent calcium antagonists.
AB  - Sympathetic neurotransmission in tissues with intact sympathetic nerve
      arborization is extensively dependent on calcium influx via N-type calcium
      channels. It was the objective of the present study to assess and compare the
      claimed sympatholytic effect of the 1,4-dihydropyridine compound cilnidipine with
      other voltage-dependent calcium-channel (VDCC) antagonists. We studied these
      compounds by means of three different models. In the rabbit isolated thoracic
      aorta, the alleged sympatholytic properties displayed by these compounds were
      evaluated in the noradrenaline spillover model. Additionally, the influence of
      cilnidipine on stimulation-induced constrictor responses was studied in the rat
      isolated tail artery (male Wistar rats, 250-300 g) in addition to its effect on
      noradrenaline-induced contractions. Finally, we studied the influence of
      cilnidipine and other calcium-channel blockers on stimulation-induced
      chronotropic responses, in order to address N- or L-type selectivity, in the
      pithed rat model (male Wistar rats, 260-320 g). Furthermore, we evaluated their
      effect on noradrenaline-induced tachycardia. In the isolated rabbit thoracic
      aorta preparation omega-conotoxin GVIA (0.1 microM) nearly abolished the
      sympathetic outflow caused by stimulation, whereas nifedipine (0.1 microM) and
      amlodipine (1 microM) did not influence the evoked noradrenaline release.
      Cilnidipine (1 microM) significantly attenuated the response by nearly 18% and
      mibefradil (1 microM) by c. 42%. The stimulation-induced constrictor response
      (prejunctional effect) in the rat isolated tail artery could be blocked by omega
      conotoxin GVIA (0.5 and 1 microM). Cilnidipine (10 nm and 0.1 microM)
      significantly attenuated responses to stimulation by maximally 20%, whereas it
      did not influence the constrictor response to noradrenaline (postjunctional
      effect). The mean heart rate in the pithed rat model amounted to 309.3 +/- 3.6
      beats/min (bpm). Electrical stimulation of the cardio-accelerator nerves (C7-Th1)
      resulted in an increase by 106.7 +/- 2.2 bpm. All antagonists studied, except for
      nifedipine, attenuated the chronotropic response to stimulation (P < 0.05). The
      rank order of sympatholytic efficacy was: omega-conotoxin GVIA (84.8%),
      mibefradil (75.1%), cilnidipine (43.0%) and amlodipine (34.8%). Noradrenaline (10
      nmol/kg) increased the heart rate by 117.8 +/- 2.7 bpm. This chronotropic
      response was influenced equally well by the calcium-channels blockers as observed
      in the stimulation (prejunctional) experiment. In conclusion, the N-type channel
      blocking properties and thus sympatholytic effect of cilnidipine could be
      demonstrated in some (vascular) but not all (cardiac) models studied. At the
      level of the vasculature cilnidipine reduced the neurotransmitter release to
      electrical stimulation in both the noradrenaline spillover model and in the model
      of the rat isolated tail artery, respectively. For amlodipine and nifedipine no
      sympatholytic activity could be demonstrated. In the pithed rat model, we were
      unable to demonstrate a selective N-type blocking effect for the VDCC
      antagonists.

PMID- 15147283
TI  - Endothelium-dependent contractions to acetylcholine, ATP and the calcium
      ionophore A 23187 in aortas from spontaneously hypertensive and normotensive
      rats.
AB  - The present study was designed to determine whether or not an increase in
      endothelial intracellular concentration of calcium ([Ca2+]i) evokes endothelium
      dependent contractions in the aorta from normotensive Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR). Acetylcholine, adenosine triphosphate
      (ATP) and the calcium ionophore, A 23187, produced endothelium-dependent
      relaxations in isolated aortic rings of both WKY and SHR. These relaxations in
      response to the three agonists were significantly smaller in the SHR when
      compared with the WKY. Endothelium-dependent contractions to acetylcholine, ATP
      and A 23187 were observed only in the aorta isolated from the SHR. In the
      presence of NG-nitro-L-arginine, an NO synthase inhibitor, the endothelium
      dependent contractions in response to acetylcholine, ATP and A 23187 were
      potentiated significantly in the aorta SHR and were unmasked in that of WKY.
      However, the contractions were still significantly greater in SHR than in WKY.
      These contractions were abolished by indomethacin and valeryl salicylate (two
      cyclo-oxygenase inhibitors) as well as by S 18886 (a TP-receptor antagonist),
      indicating that the endothelium-dependent contraction produced by the three
      agonists share the same characteristics. The results of the present study
      indicate that the release/generation of endothelium-derived contracting factor,
      requires an increase in endothelial [Ca2+]i.

PMID- 15147284
TI  - Does treatment with gum Arabic affect experimental chronic renal failure in rats?
AB  - The effect of treatment with gum Arabic in rats with experimental chronic renal
      failure (CRF) was investigated. Some rats underwent two-stage surgical
      nephroectomy to induce CRF, and some were sham-operated. Gum Arabic was then
      given to rats in the drinking water at doses of 3 or 6 g/100 mL/day for five
      consecutive weeks. Thereafter, rats were killed and the concentrations of urea
      and creatinine measured in their plasma. Body weights of all rats were taken
      every week during the experimental period. The significant increases in the
      concentrations of urea and creatinine, induced by experimental CRF were slightly
      and insignificantly (P > 0.05) decreased by gum Arabic by about 8 and 13% in rats
      treated at doses of 3 and 6 g/100 mL/day in the drinking water, respectively.
      Treatment with gum Arabic at the two doses did not significantly reverse the
      decrease in body weight in CRF rats.

PMID- 15147285
TI  - Polyphenolic compounds from Cognac induce vasorelaxation in vitro and decrease
      post-ischaemic cardiac infarction after an oral administration.
AB  - The effects of Cognac polyphenolic compounds (CPC) on aorta and isolated heart,
      the consequences of oral administration on haemodynamic parameters, vascular
      reactivity and cardiac recovery after ischaemia were investigated. CPC induced an
      endothelium-dependent vasorelaxation on rat-isolated aorta. This effect was
      prevented by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine-methyl
      ester, but not by the cyclo-oxygenase inhibitor, indomethacin, suggesting the
      implication of NO pathway. On isolated rat hearts, CPC induced positive
      inotropic, chronotropic, and lusitropic effect at 10(-4)-10(-2) g/L while at 10(
      1) g/L, it had negative lusitropic effect and other parameters returned to
      baseline values. Oral administration of 40 mg/kg of CPC for 2 weeks did not
      modify systolic blood pressure and heart rate of rats throughout the treatment.
      CPC treatment did not affect ex vivo response of isolated thoracic aorta either
      to the contractile agent noradrenaline or to the endothelial-relaxant agent,
      acetylcholine. Isolated hearts from treated rats were submitted to 30-min global
      ischaemia followed by 120 min of reperfusion. Post-ischaemic recovery of
      functional cardiac parameters was not modified by treatment with CPC. Infarct
      size measured after the reperfusion in heart from CPC-treated rats was
      significantly decreased in comparison with hearts from control group. We conclude
      that in vitro, CPC had NO-dependent vasorelaxant effects and stimulated cardiac
      function. Oral treatment with CPC appeared to have no impact in vivo on blood
      pressure, heart rate of the rats or on cardiac contractility ex vivo; however, it
      could decrease the infarct size after an ischaemia-reperfusion.

PMID- 15147286
TI  - Glucose levels observed in daily clinical practice induce endothelial dysfunction
      in the rabbit macro- and microcirculation.
AB  - We investigated whether different concentrations of elevated glucose -
      corresponding to levels observed in patients with type 2 diabetes under routine
      care (post-prandial mean and maximum values) and those used for diagnosing
      diabetes - induce impairment of vascular reactivity of the macro- and
      microcirculation in non-diabetic rabbits. Aortic rings and isolated perfused
      kidneys from normal rabbits were acutely exposed (3 h) to normal (5.5 mm) or high
      (7-25 mM) D-glucose concentrations. Vascular reactivity was evaluated with
      endothelium-dependent [acetylcholine (ACh) and bradykinin (BK)] and independent
      [sodium nitroprusside (SNP)] vasodilating agents. Endothelium-dependent
      relaxation of the thoracic aorta induced by ACh or BK was significantly
      attenuated after a 3-h exposure to high D-glucose (15-25 mM) but not after
      corresponding increased osmolarity with mannitol solutions. Relaxation induced by
      SNP (endothelium-independent) was not affected by high D-glucose concentrations.
      Moreover, endothelium-dependent but not independent vasodilation of the isolated
      rabbit kidney was also impaired after 3-h perfusion with high D-glucose (11.1-25
      mM). Perfusion with mannitol solutions (15-25 mM) partially blunted endothelium
      dependent renal vasodilation. It is concluded that acute hyperglycemia
      corresponding to post-prandial levels in patients with type 2 diabetes induces
      endothelial dysfunction of conduit vessels as well as of the renal circulation of
      non-diabetic rabbits.

PMID- 15147287
TI  - Sedation in children undergoing CT scan or MRI: effect of time-course and
      tolerance of rectal chloral hydrate.
AB  - The aim of this paper was to describe the time-course of the sedative effect of
      rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty
      children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate
      rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin,
      Germany), before a CT scan or an NMR imaging. Sedation was measured at specific
      times using a sedation score of 1-6. Patients were continuously monitored for
      respiratory and heart rate, systolic and diastolic blood pressures, and oxygen
      saturation. About 82.35 and 94.11% of the patients had a score of sedation > or =
      3 within 15 and 30 min, respectively. The mean time to effective sedation (score
      > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of
      effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75
      h). A total of 93.1% of the X-ray sections were obtained without artifact and
      sedation was considered by radiologists to be efficient for 83.3% of the
      procedures. This sedation procedure appeared efficient and safe during ambulatory
      CT scan and NMR imaging. The long-term effect of chloral hydrate, however,
      remains to be evaluated.

PMID- 15147288
TI  - Assessment of patient-reported outcomes in clinical trials: the example of health
      related quality of life.
AB  - As the patient is the primary recipient of treatment, there is a need to
      recognize and value the patient's perception of change in response to treatment
      in clinical trials. A new outcomes classification, patient-reported outcomes
      (PROs), has been proposed by regulators. The PROs are used as an umbrella term
      and include, for example measures of subjective symptoms, health-related quality
      of life (HRQL) and treatment satisfaction. In this sense, the PROs are unique and
      complementary indicators of disease activity as well as of treatment efficacy.
      Frequently, pharmaceutical companies desire to include PRO benefits in the
      product label in order to reach a broad range of customers, including prescribers
      as well as patients. Therefore such information must be based on results that are
      scientifically valid. The measurement strategy, i.e. the thinking about and
      decision-making related to PRO and HRQL evaluations, needs to be explicit for
      clinical trials. First of all it is necessary to specify and provide the
      rationale for measuring the PROs. Similarly, the reason for selecting particular
      instruments should be stated and, for the selected instruments, the psychometric
      evidence should be summarized. The key PRO domains must be prespecified and
      evidence of their importance to patients should be provided. The research
      question under study and potential claims need to be clearly delineated. Hence,
      instrument selection is a key initial step for planning successful and
      scientifically adequate clinical trials intended to support labelling and
      promotional claims of PRO benefits to patients. The scientific criteria and
      design issues of clinical trials are the same for clinical and PRO endpoints.
      However, important issues of particular relevance to PRO assessments, such as
      missing values, multiple outcomes, and the statistical analysis, require careful
      attention. The thinking and planning involved in developing the PRO component of
      the clinical trial need to be articulated. Successful evaluation of PROs in
      clinical trials relies on careful planning provided the treatment shows
      sufficient effectiveness.

PMID- 15147289
TI  - Level of evidence and therapeutic evaluation: need for more thoughts.
AB  - The practice of evidence-based medicine requires a tool to assess and
      discriminate available data based on objective grounds, thus facilitating access
      to reliable information. The level of evidence, conceptually and practically
      embedded in scientific activity, allows comparing the results from multiple
      studies testing an identical hypothesis along the lines of at least two
      dimensions. The first dimension deals with the design of the study, i.e. the
      extent to which bias is avoided or managed, the second with the quality of
      incorporated data. A third dimension specific to therapeutic evaluation focuses
      on the clinical relevance of the tested hypothesis. The concern of the final user
      of the information is thus put to the fore. Indeed, a general practitioner will
      be interested in the benefit for its patients whereas the concern of a biologist
      might significantly diverge from the former matter. The bulk of existing scales
      of level of evidence concentrate on methodology. Some may include the second
      dimension but none embrace the three of them. Seldom considered are matters
      regarding reproducibility and procedure. This is all the more unfortunate as
      reproducibility is a cornerstone of scientific progress. Moreover, scales used
      for overviews fail to take into account the methodology designed to produce the
      synthesis. Inconsistent existing scales prevent the emergence of a generally
      agreed standard. Therefore, there is a need to further specify the concept of
      level of evidence in therapy evaluation and design scales encompassing the three
      above-mentioned dimensions: methodology of experiment, quality of data, and
      clinical relevance of the primary criterion.

PMID- 15147290
TI  - Choice of designs and doses for early phase trials.
AB  - This paper reviews state-of-art statistical designs for dose-escalation
      procedures in first-into-man studies. The main focus will be on studies in
      oncology, as most statistical procedures for phase I trials have been proposed in
      this context. Extensions to situations such as the observation of bivariate
      outcomes and healthy volunteer studies are also discussed. The number of dose
      levels and cohort sizes used in early phase trials are considered. Finally, this
      paper raises some practical issues for dose-escalation procedures.

PMID- 15147291
TI  - Hypnotic and tranquillizer use among general practitioners in south-eastern
      France and its relation to occupational characteristics and prescribing habits.
AB  - Previous research suggests that practising physicians are more likely than the
      general population to use psychotropic drugs. Hypnotic and tranquillizer use in
      France is among the highest in Europe; most hypnotic and tranquillizer
      prescriptions are written by general practitioners (GPs). The objective was to
      compare the hypnotic and tranquillizer use of GPs in private practice in Provence
      (south-eastern France) with that of the general population and to study factors
      associated with physicians' hypnotic and tranquillizer use. A cross-sectional
      telephone survey was carried out with a panel of 600 GPs in Provence. The data
      were collected with a 53-item questionnaire about their social and demographic
      status, family, occupation, training, information-seeking behaviour, job
      satisfaction, hypnotic and tranquillizer drug use, tranquillizer and
      antidepressant prescriptions. The data were analysed using univariate and
      backward multiple logistic regressions. We found that GPs in Provence use
      hypnotics and tranquillizers at a significantly higher rate than the general
      population. We found significant associations with hypnotic and tranquillizer use
      only among the older group of GPs (older than 48 years). In this group, this drug
      use was related to the volume of services provided (billing sector), job
      dissatisfaction, lack of training, the 'family burden' and tranquillizer
      prescriptions. The strains associated with both medical practice and family
      burden have some influence on hypnotic and tranquillizer use among GPs;
      individual factors may influence prescribing attitudes and patient care as well.

PMID- 15147292
TI  - Blood pressure and heart rate variability changes during cardiac surgery with
      cardiopulmonary bypass.
AB  - This study investigated patients undergoing elective cardiac surgery to evaluate
      the effects of cardiopulmonary bypass (CPB) on the spontaneous variability of
      mean arterial pressure (MAP) and heart rate (HR). Forty-one adult patients
      receiving different cardiovascular system drugs were included in the study.
      Patients were divided into three groups: no preoperative pharmacological
      cardiovascular treatment (n = 12), beta-blocker (BB) (n = 13), and angiotensin
      converting enzyme inhibition (ACEI) (n = 16). MAP was recorded before anaesthesia
      until the end of surgery. MAP and HR variability was analysed in very low- (VLF),
      low- (LF) and high-frequency bands. The LF spectral component of MAP was observed
      to decrease in patients under ACEI (-92%) or BB (-87%) following induction of
      anaesthesia. In addition, during CPB, VLF power decreased in BB group (-67%), and
      LF power decreased in ACEI group (-77%). Concerning HR, VLF spectral power
      decreased following anaesthesia in BB group (-74%). In addition, after CPB, VLF
      power reached lower value in ACEI group than in BB group (P < 0.05). LF spectral
      power of HR showed a large decrease after CPB in ACEI group (-89%). This study
      showed that MAP variability did not change during CPB in patients with no
      preoperative pharmacological cardiovascular treatment, suggesting an unaltered
      vascular control of MAP. Moreover, the change in LF spectral power of MAP in ACEI
      and BB groups, suggests that both the renin-angiotensin and sympathetic systems
      participate to the genesis of LF variability of MAP.

PMID- 15147295
TI  - Differential regulation of the mitochondrial and death receptor pathways in
      neural stem cells.
AB  - Despite an increasing interest in neural stem cell (NSC) research, relatively
      little is known about the biochemical regulation of cell death pathways in these
      cells. We demonstrate here, using murine-derived multipotent C17.2 NSCs, that
      cells undergo mitochondria-mediated cell death in response to apoptotic stimuli
      such as oxidative stress induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). In
      particular, treated cells exhibited apoptotic features, including Bax
      translocation, cytochrome c release, activation of caspase-9 and -3, chromatin
      condensation and DNA fragmentation. Although C17.2 cells possess the Fas receptor
      and express procaspase-8, agonistic Fas mAb treatment failed to induce apoptosis.
      Fas treatment activated the extracellular signal-regulated protein kinase (ERK)
      pathway, which may have an antiapoptotic as well as a growth stimulating role.
      Combined, our findings indicate that while NSCs are sensitive to cytotoxic
      stimuli that involve an engagement of mitochondria, Fas treatment does not induce
      death and may have an alternative role.

PMID- 15147296
TI  - Plexin-B family members demonstrate non-redundant expression patterns in the
      developing mouse nervous system: an anatomical basis for morphogenetic effects of
      Sema4D during development.
AB  - Semaphorins and their receptors play important roles in patterning the
      connectivity of the developing nervous system and recent data suggest that
      members of the plexin-B family of semaphorin receptors may be involved in axonal
      guidance. Here we show that the mRNAs of the three plexin-B genes, plxnb1, plxnb2
      and plxnb3 (plexin-B1, plexin-B2 and plexin-B3), respectively, are expressed in
      highly specific and non-redundant patterns in peripheral and central components
      of the nervous system over defined periods during murine development. Whereas
      plexin-B1 and plexin-B2 are strongly expressed in the neuroepithelium and
      developing neurons, plexin-B3 mRNA is selectively localized to the white matter.
      Moreover, plexin-B1 and its ligand Sema4D are expressed in complementary patterns
      in several regions such as the developing neopallial cortex, the dorsal root
      ganglia and the spinal cord over embryonic stages. The Sema4d gene demonstrates a
      dramatic switch from prenatal expression in neuronal populations to a postnatal
      expression in oligodendrocytes. In contrast to its collapsing activity on growth
      cones of embryonic retinal ganglion cells and hippocampal neurons, soluble Sema4D
      enhances axonal outgrowth in embryonic cortical explants cultured in collagen
      matrices. Thus, plexin-B family members and Sema4D are likely to play complex and
      non-redundant roles during the development of the nervous system.

PMID- 15147297
TI  - Functional expression of connexin57 in horizontal cells of the mouse retina.
AB  - Horizontal cells are interneurons of the vertebrate retina that exhibit strong
      electrical and tracer coupling but the identity of the channel-forming connexins
      has remained elusive. Here we show that horizontal cells of the mouse retina
      express connexin57 (Cx57). We have generated Cx57-deficient mice by replacing the
      Cx57 coding region with a lacZ reporter gene, expressed under control of the
      endogenous Cx57 promoter. These mice were fertile and showed no obvious
      anatomical or behavioural abnormalities. Cx57 mRNA was expressed in the retina of
      wild-type littermates but was absent from the retina of Cx57-deficient mice.
      Previously reported results that the Cx57 gene was very weakly expressed in
      several other mouse tissues turned out to be unspecific. Cx57 mRNA is abundantly
      expressed in the retina and weakly in the thymus of adult mice but absent in all
      other adult tissues tested, including brain. Furthermore, Cx57 is expressed in
      embryonic kidney at E16.5 to E18.5 days post-conception, as indicated by the
      pattern of lacZ expression. Within the retina, lacZ signals were assigned
      exclusively to horizontal cells based on co-localization with cell-type-specific
      marker proteins. Microinjection of Neurobiotin into horizontal cells of isolated
      retinae revealed less than 1% of tracer coupling in Cx57-deficient retinae
      compared with wild-type controls. Cx57 is the first connexin identified in
      mammalian horizontal cells and the first connexin whose expression is apparently
      restricted to only one type of neuron.

PMID- 15147298
TI  - GABAB receptors in Schwann cells influence proliferation and myelin protein
      expression.
AB  - The location and the role of gamma-aminobutyric acid type B (GABA(B)) receptors
      in the central nervous system have recently received considerable attention,
      whilst relatively little is known regarding the peripheral nervous system. In
      this regard, here we demonstrate for the first time that GABA(B) receptor
      isoforms [i.e. GABA(B(1)) and GABA(B(2))] are specifically localized in the rat
      Schwann cell population of the sciatic nerve. Using the selective GABA(B) agonist
      [i.e. (-)-baclofen] and the antagonists (i.e. CGP 62349, CGP 56999 A, CGP 55845
      A), such receptors are shown to be functionally active and negatively coupled to
      the adenylate cyclase system. Furthermore, exposure of cultured Schwann cells to
      (-)-baclofen inhibits their proliferation and reduces the synthesis of specific
      myelin proteins (i.e. glycoprotein Po, peripheral myelin protein 22, myelin
      associated glycoprotein, connexin 32), providing evidence for a physiological
      role of GABA(B) receptors in the glial cells of the peripheral nervous system.

PMID- 15147299
TI  - Suppression of a slow post-spike afterhyperpolarization by calcineurin
      inhibitors.
AB  - A subset of myenteric neurons in the intestine (AH neurons) generate prolonged
      (>5 s) post-spike afterhyperpolarizations (slow AHPs) that are insensitive to
      apamin and tetraethylammonium. Generation of slow AHPs depends critically on
      Ca(2+) entry and intracellular release of Ca(2+) from stores, which then leads to
      the activation of a K(+) conductance that underlies the slow AHP (g(sAHP)). Slow
      AHPs are inhibited by stimulation of the cAMP/protein kinase A (PKA) pathway,
      suggesting that phosphorylation of the K(+)-channels that mediate the g(sAHP)
      (K(sAHP)-channels) is responsible for suppression of slow AHPs and possibly for
      the repolarization phase of slow AHPs. In the present study, we investigated the
      possibility that the rising phase of the slow AHP is mediated by
      dephosphorylation of K(sAHP)-channels by calcineurin (CaN), a Ca(2+)-calmodulin
      dependent protein phosphatase, leading to an increase in g(sAHP) and activation
      of the associated current I(sAHP). Slow AHPs and I(sAHP) were recorded using
      conventional recording techniques, and we tested the actions of two inhibitors of
      CaN, FK506 and cyclosporin A, and also the effect of the CaN autoinhibitory
      peptide applied intracellularly, on these events. We report here that all three
      treatments inhibited the slow AHP and I(sAHP) (>70%) without significantly
      affecting the ability of neurons to fire action potentials. In addition, the slow
      AHP and I(sAHP) were suppressed by okadaic acid, an inhibitor of protein
      phosphatases 1 and 2A. Our results indicate that activation of the g(sAHP) that
      underlies the post-depolarization slow AHPs in AH neurons is mediated by the
      actions CaN and non-Ca(2+)-dependent phosphatases.

PMID- 15147300
TI  - The cytosolic II-III loop of Cav2.3 provides an essential determinant for the
      phorbol ester-mediated stimulation of E-type Ca2+ channel activity.
AB  - There is growing evidence that E-type voltage dependent Ca(2+) channels
      (Ca(v)2.3) are involved in triggering and controlling pivotal cellular processes
      like neurosecretion and long-term potentiation. The mechanism underlying a novel
      Ca(2+) dependent stimulation of E-type Ca(2+) channels was investigated in the
      context of the recent finding that influx of Ca(2+) through other voltage
      dependent Ca(2+) channels is necessary and sufficient to directly activate
      protein kinase C (PKC). With Ba(2+) as charge carrier through Ca(v)2.3 channel
      alpha(1) subunits expressed in HEK-293 cells, activation of PKC by low
      concentrations of phorbol ester augmented peak I(Ba) by approximately 60%. In
      addition, the non-inactivating fraction of I(Ba) was increased by more than three
      fold and recovery from short-term inactivation was accelerated. The effect of
      phorbol ester on I(Ba) was inhibited by application of the specific PKC inhibitor
      bisindolylmaleimide I. With Ca(2+) as charge carrier, application of phorbol
      ester did not change the activity of Ca(v)2.3 currents but they were modified by
      the PKC inhibitor bisindolylmaleimide I. These results suggest that with Ca(2+)
      as charge carrier the incoming Ca(2+) can activate PKC, thereby augmenting Ca(2+)
      influx into the cytosol. No modulation of Ca(v)2.3 channels by PKC was observed
      when an arginine rich region in the II-III loop of Ca(v)2.3 was eliminated.
      Receptor independent stimulation of PKC and its interaction with Ca(v)2.3
      channels therefore represents an important positive feedback mechanism to decode
      electrical signals into a variety of cellular functions.

PMID- 15147301
TI  - Elevation of intracellular cAMP evokes activity-dependent release of adenosine in
      cultured rat forebrain neurons.
AB  - Adenosine is an important regulator of neuronal excitability. Zaprinast is a
      cyclic nucleotide phosphodiesterase inhibitor, and has been shown in the
      hippocampal slice to suppress excitation. This action can be blocked by an
      adenosine receptor antagonist, and therefore is presumably due to adenosine
      release stimulated by exposure to zaprinast. To explore the mechanism of this
      phenomenon further, we examined the effect of zaprinast on adenosine release
      itself in cultured rat forebrain neurons. Zaprinast significantly stimulated
      extracellular adenosine accumulation. The effect of zaprinast on adenosine
      appeared to be mediated by increasing intracellular cyclic adenosine
      monophosphate (cAMP) and activation of protein kinase A (PKA): (i) zaprinast
      stimulated intracellular cAMP accumulation; (ii) a cAMP antagonist (Rp-8-Br-cAMP)
      significantly reduced the zaprinast effect on adenosine; (iii) an inhibitor of
      phosphodiesterase (PDE)1 (vinpocetine) and an activator of adenylate cyclase
      (forskolin) mimicked the effect of zaprinast on adenosine. We also found that
      zaprinast had no effect on adenosine in astrocyte cultures, and tetrodotoxin
      completely blocked zaprinast-evoked adenosine accumulation in neuronal cultures,
      suggesting that neuronal activity was likely to be involved. Consistent with a
      dependence on neuronal activity, NMDA receptor antagonists (MK-801 and D-APV) and
      removal of extracellular glutamate by glutamate-pyruvate transaminase blocked the
      effect of zaprinast. In addition, zaprinast was shown to stimulate glutamate
      release. Thus, our data suggest that zaprinast-evoked adenosine accumulation is
      likely to be mediated by stimulation of glutamate release by a cAMP- and PKA
      dependent mechanism, most likely by inhibition of PDE1 in neurons. Furthermore,
      regulation of cAMP, either by inhibiting cAMP-PDE activity or by stimulating
      adenylate cyclase activity, may play an important role in modulating neuronal
      excitability. These data suggest the existence of a homeostatic negative feedback
      loop in which increases in neuronal activity are damped by release of adenosine
      following activation of glutamate receptors.

PMID- 15147302
TI  - Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2
      mediated direct suppression and M1/M3-mediated indirect suppression through
      endocannabinoid signalling.
AB  - The cholinergic system in the CNS plays important roles in higher brain
      functions, primarily through muscarinic acetylcholine receptors. At cellular
      levels, muscarinic activation produces various effects including modulation of
      synaptic transmission. Here we report that muscarinic activation suppresses
      hippocampal inhibitory transmission through two distinct mechanisms, namely a
      cannabinoid-dependent and cannabinoid-independent mechanism. We made paired whole
      cell recordings from cultured hippocampal neurons of rats and mice, and monitored
      inhibitory postsynaptic currents (IPSCs). When cannabinoid receptor type 1 (CB1)
      was blocked, oxotremorine M (oxo-M), a muscarinic agonist, suppressed IPSCs in a
      subset of neuron pairs. This suppression was associated with an increase in
      paired-pulse ratio, blocked by the M(2)-preferring antagonist gallamine, and was
      totally absent in neuron pairs from M(2)-knockout mice. When CB1 receptors were
      not blocked, oxo-M suppressed IPSCs in a gallamine-resistant manner in
      cannabinoid-sensitive pairs. This suppression was associated with an increase in
      paired-pulse ratio, blocked by the CB1 antagonist AM281, and was completely
      eliminated in neuron pairs from M(1)/M(3)-compound-knockout mice. Our
      immunohistochemical examination showed that M(2) and CB1 receptors were present
      at inhibitory presynaptic terminals of mostly different origins. These results
      indicate that two distinct mechanisms mediate the muscarinic suppression. In a
      subset of synapses, activation of M(2) receptors at presynaptic terminals
      suppresses GABA release directly. In contrast, in a different subset of synapses,
      activation of M(1)/M(3) receptors causes endocannabinoid production and
      subsequent suppression of GABA release by activating presynaptic CB1 receptors.
      Thus, the muscarinic system can influence hippocampal functions by controlling
      different subsets of inhibitory synapses through the two distinct mechanisms.

PMID- 15147303
TI  - Newly developed blockers of the M-current do not reduce spike frequency
      adaptation in cultured mouse sympathetic neurons.
AB  - The M-current (I(K(M))) is believed to modulate neuronal excitability by
      producing spike frequency adaptation (SFA). Inhibitors of M-channels, such as
      linopirdine and 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE991), enhance
      depolarization-induced transmitter release and improve learning performance in
      animal models. As such, they are currently being tested for their therapeutic
      potential for treating Alzheimer's disease. The activity of these blockers has
      been associated with the reduction of SFA and the depolarization of the membrane
      observed when I(K(M)) is inhibited. To test whether this is the case, the
      perforated patch technique was used to investigate the capacity of I(K(M))
      inhibitors to alter the resting membrane potential and to reduce SFA in mouse
      superior cervical ganglion neurons in culture. Linopirdine and XE991 both proved
      to be potent blockers of I(K(M)) when the membrane potential was held at -30 mV
      (IC(50) 2.56 and 0.26 microM, respectively). However, their potency gradually
      declined upon membrane hyperpolarization and was almost null when the membrane
      potential was kept at -70 mV, indicating that their blocking activity was voltage
      dependent. Nevertheless, I(K(M)) could be inhibited at these hyperpolarized
      voltages by other inhibitors such as oxotremorine-methiodide and barium. Under
      current-clamp conditions, neither linopirdine (10 microM) nor XE991 (3 microM)
      was effective in reducing the SFA and both provoked only a small slowly developed
      depolarization of the membrane (2.27 and 3.0 mV, respectively). In contrast, both
      barium (1 mM) and oxotremorine-methiodide (10 microM) depolarized mouse superior
      cervical ganglion neurons by about 10 mV and reduced the SFA. In contrast to
      classical I(K(M)) inhibitors, the activity of linopirdine and XE991 on the
      I(K(M)) is voltage dependent and, thus, these newly developed I(K(M)) blockers do
      not reduce the SFA. These results may shed light on the mode of action of these
      putative cognition enhancers in vivo.

PMID- 15147305
TI  - Increased MAP kinase activity in Alzheimer's and Down syndrome but not in
      schizophrenia human brain.
AB  - Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which
      develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also
      recognized as a clinical characteristic of schizophrenia, which does not appear
      to be associated with tau-aggregate formation. Several kinases can phosphorylate
      tau in cell-free assays. Here we show increased activity of mitogen-activated
      protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and
      DS brains, which could not be accounted for by expression changes. In contrast,
      glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly.
      Examination of tau in AD and DS using antibodies selective for MAPK
      phosphorylation sites showed increased immunoreactivity. In addition,
      phosphorylation of S(199), reportedly a selective substrate for cyclin-dependent
      kinase-5 (cdk5) or GSK-3 alpha beta was only observed in AD samples, which showed
      a concomitant increase in the expression of p25, the enhancing cofactor for cdk5
      activity. However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged
      compared to matched controls, despite similar expression levels to those in AD.
      The activities of the MAPKs and GSK-3 alpha beta were also unchanged. These data
      demonstrate that in AD and DS, enhanced MAPK activity, which has an established
      role in regulating neuronal plasticity and survival, can account for irregular
      tau phosphorylation, and that the molecular processes involved in these
      neurodegenerative disorders are distinct from those in schizophrenia. These data
      also question the significance of GSK-3 alpha beta, as much previous work carried
      out in vitro has placed this kinase as a favoured candidate for involvement in
      the pathological phosphorylation of tau.

PMID- 15147304
TI  - Nicotine reduces A beta in the brain and cerebral vessels of APPsw mice.
AB  - Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha
      beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more
      than that observed in 14.5-month-old mice following nicotine treatment for 5.5
      months. A reduction in A beta associated with cerebral vessels was observed in
      addition to that deposited as parenchymal plaques after 5.5 months treatment. The
      diminution in A beta peptides observed was not accompanied by changes in brain
      alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression
      measured in brain homogenates. A significant increase in sAPP was observed after
      nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the
      nicotinic antagonist mecamylamine. Attenuation of elevated [(125)I]-alpha
      bungarotoxin binding (alpha 7) in APPsw mice was observed after 5.5 months
      nicotine treatment. Both these observations suggest that the reduction in
      insoluble A beta by nicotine might be in part mediated via the alpha 7 nicotinic
      receptor. Further studies are required to identify potential mechanisms of the
      nicotine's amyloid-reducing effect.

PMID- 15147306
TI  - GABAergic modulation of DC stimulation-induced motor cortex excitability shifts
      in humans.
AB  - Weak transcranial DC stimulation (tDCS) of the human motor cortex results in
      excitability shifts during and after the end of stimulation, which are most
      probably localized intracortically. Anodal stimulation enhances excitability,
      whereas cathodal stimulation reduces it. Although the after-effects of tDCS are
      NMDA receptor-dependent, nothing is known about the involvement of additional
      receptors. Here we show that pharmacological strengthening of GABAergic
      inhibition modulates selectively the after-effects elicited by anodal tDCS.
      Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed,
      but then enhanced and prolonged anodal tDCS-induced excitability elevation. The
      initial absence of an excitability enhancement under lorazepam is most probably
      caused by a loss of the anodal tDCS-generated intracortical diminution of
      inhibition and enhancement of facilitation, which occurs without pharmacological
      intervention. The reasons for the late-occurring excitability enhancement remain
      unclear. Because intracortical inhibition and facilitation are not changed in
      this phase compared with pre-tDCS values, excitability changes originating from
      remote cortical or subcortical areas could be involved.

PMID- 15147307
TI  - Depression of GABAergic input to identified hippocampal neurons by group III
      metabotropic glutamate receptors in the rat.
AB  - The release of GABA in synapses is modulated by presynaptic metabotropic
      glutamate receptors (mGluRs). We tested whether GABA release to identified
      hippocampal neurons is influenced by group III mGluR activation using the agonist
      L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) on inhibitory postsynaptic currents
      (IPSCs) evoked in CA1 interneurons and pyramidal cells. In interneurons,
      characterized with biocytin and immunolabelling for somatostatin, evoked IPSCs
      were depressed by 50 micro m L-AP4 (activating mGluR4 and 8) to 68 +/- 6% of
      control, but they were rarely depressed in pyramidal cells (96 +/- 4% of
      control). At 300-500 micro m concentration (activating mGluR4, 7 and 8), L-AP4
      depressed IPSCs in both interneurons (to 70 +/- 6%) and pyramidal cells (to 67 +/
      4%). The change in trial-to-trial variability and in paired-pulse depression
      indicated a presynaptic action. In interneurons, the degree of IPSC depression
      was variable (to 9-87%), and a third of IPSCs were not affected by L-AP4. The L
      AP4-evoked IPSC depression was blocked by LY341495. The depression of IPSCs was
      similar in O-LM cells and other interneurons. The lack of cell-type selectivity
      and the similar efficacy of different concentrations of L-AP4 suggest that
      several group III mGluRs are involved in the depression of IPSCs. Electron
      microscopic immunocytochemistry confirmed that mGluR4, mGluR7a and mGluR8a occur
      in the presynaptic active zone of GABAergic terminals on interneurons, but not on
      those innervating pyramidal cells. The high variability of L-AP4-evoked IPSC
      suppression is in line with the selective expression of presynaptic mGluRs by
      several distinct types of GABAergic neuron innervating each interneuron type.

PMID- 15147309
TI  - A parvalbumin-containing, axosomatic synaptic network in the rat medial septum:
      relevance to rhythmogenesis.
AB  - The medial septal diagonal band complex (MS/DB), made up of cholinergic and
      GABAergic neurons, plays an important role in the generation of the hippocampal
      theta rhythm. A GABAergic neuron type in the MS/DB that has fast spiking
      properties was shown previously to contain parvalbumin immunoreactivity and to
      form axosomatic connections with unidentified somata. The aim in the current
      study was to determine the neurochemical identities of these target neurons. In
      slices and in perfused-fixed brain, staining for parvalbumin immunoreactivity
      first of all revealed the presence of two types of parvalbumin-positive somata in
      the MS/DB: medially located neurons with parvalbumin-positive basket-like
      terminals on them, and more laterally located neurons with fewer parvalbumin
      positive contacts on them. In MS/DB slices, the terminals of fast spiking neurons
      filled with biocytin correspondingly made either numerous contacts that
      surrounded the parvalbumin-positive cell body in basket-like formation, or 1-5
      contacts on a localized patch of the soma. These contacts were shown by electron
      microscopy to form synaptic junctions. No terminals of biocytin-filled fast
      spiking neurons were observed on cholinergic neurons, and dual staining in
      perfused-fixed brain did not reveal the presence of parvalbumin-containing
      terminals on cholinergic somata. Our results suggest therefore that there are two
      subtypes of parvalbumin-containing neuron in the MS/DB, and that these are
      interconnected via axosomatic synapses. The contrasting topographical
      organization of the two types of parvalbumin-containing neuron suggests that they
      may receive different types of afferent input, but this will require
      substantiation in future studies. We propose that generation of rhythmic activity
      in the MS/DB is controlled by contrasting contributions from two types of
      parvalbumin-positive neuron, and that the role of the cholinergic neuron is
      modulatory.

PMID- 15147308
TI  - Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin
      neurotoxic lesions of the dorsolateral pons on sleep and muscle tone.
AB  - The hypocretin neurons have been implicated in regulating sleep-wake states as
      they are lost in patients with the sleep disorder narcolepsy. Hypocretin (HCRT)
      neurons are located only in the perifornical region of the posterior hypothalamus
      and heavily innervate pontine brainstem neurons, such as the locus coeruleus
      (LC), which have traditionally been implicated in promoting arousal. It is not
      known how the hypocretin innervation of the pons regulates sleep-wake states as
      pontine lesions have never been shown to increase sleep. It is likely that in
      previous studies specific neurons were not lesioned. Therefore, in this study, we
      applied saporin-based neurotoxins to the dorsolateral pons and monitored sleep in
      rats. Anti-dopamine-beta-hydroxylase-saporin killed the LC neurons but sleep was
      affected only during a two hour light-dark transition period. Application of
      hypocretin2-saporin killed fewer LC neurons relative to other adjacent neurons.
      This occurred because the LC neurons possess the hypocretin receptor 1 but the
      ligand hypocretin 2 binds to this receptor with less affinity relative to the
      hypocretin receptor 2. The hypocretin2-saporin lesioned rats compared to controls
      had increased sleep during the dark period and displayed increased limb movements
      during REM sleep. None of the lesioned rats had sleep onset REM sleep periods or
      cataplexy. We conclude that the hypocretin innervation to the pons functions to
      awaken the animal when the lights turn off (via its innervation of the LC),
      sustains arousal and represses sleep during the rest of the night (via a wider
      innervation of other pontine neurons), and modulates muscle tone.

PMID- 15147310
TI  - Persistent sodium current in subicular neurons isolated from patients with
      temporal lobe epilepsy.
AB  - The persistent sodium current is a common target of anti-epileptic drugs and
      contributes to burst firing. Intrinsically burst firing subicular neurons are
      involved in the generation and spread of epileptic activity. We measured whole
      cell sodium currents in pyramidal neurons isolated from the subiculum resected in
      drug-resistant epileptic patients and in rats. In half of the cells from both
      patients and rats, the sodium current inactivated within 500 ms at -30 mV. Others
      displayed a tetrodotoxin-sensitive slowly or non-inactivating sodium current of
      up to 53% of the total sodium current amplitude. Compared with the transient
      sodium current in the same cells, this persistent sodium current activated with
      normal kinetics but its voltage-dependent activation occurred 7 mV more
      hyperpolarized. Depolarizing voltage steps that lasted 10 s completely
      inactivated the persistent sodium current. Its voltage dependence did not differ
      from that of the transient sodium current but its slope was less steep. The
      voltage dependence and kinetics of the persistent sodium current in cells from
      patients were not different from that in subicular cells from rats. The current
      density and the relative amplitude contribution were 3-4 times greater in neurons
      from drug-resistant epilepsy patients. The abundant presence of persistent sodium
      current in half of the subicular neurons could lead to a larger number of neurons
      with intrinsic burst firing. The extraordinarily large amplitude of the
      persistent sodium current in this subset of subicular neurons might explain why
      these patients are susceptible to seizures and hard to treat pharmacologically.

PMID- 15147311
TI  - Short-term exposure to constant light promotes strong circadian phase-resetting
      responses to nonphotic stimuli in Syrian hamsters.
AB  - Behavioral (nonphotic) stimuli can shift circadian rhythms by serotonin (5-HT)
      and/or neuropeptide Y (NPY) inputs to the suprachiasmatic nucleus (SCN) circadian
      clock. Based on the idea that behavioral phase resetting is modulated by
      endogenous changes in postsynaptic sensitivity to such transmitters, hamsters
      were exposed to constant light (LL; approximately 250 lx) for 1-3 days, which
      suppresses locomotor activity and eliminates the daily rhythm of SCN 5-HT release
      measured by microdialysis. Groups subjected to brief LL or maintained under a
      light/dark cycle (LD) received phase-resetting treatments with the 5-HT(1A,7)
      agonist (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH
      DPAT) or sleep deprivation (SD). Animals were released to constant darkness at
      the start of the treatments. Phase advances to 8-OH-DPAT and SD during the day
      were 11 and 3 h for LL vs. 2 and 1 h for LD, respectively. Phase delays during
      the night were -12 and -5 h for LL vs. no responses for LD, respectively. Phase
      transition curves for both LL treatments had slopes approximating 0, indicative
      of Type 0 phase resetting. For all treatments, the degree of locomotor
      suppression by LL was not correlated with the phase shift magnitude. Re
      establishing locomotor activity by overnight food deprivation did not prevent
      potentiated shifting to SD. However, re-establishing peak extracellular 5-HT
      levels by intra-SCN 5-HT reverse microdialysis perfusion in LL did significantly
      reduce potentiated 8-OH-DPAT phase advances. Constant light also enhanced intra
      SCN NPY-induced phase advances during the day (6 vs. 2 h for LD). These results
      suggest that LL promotes Type 0 phase resetting by supersensitizing 5-HT and/or
      NPY postsynaptic responses and possibly by attenuating the amplitude of the
      circadian pacemaker, thus enhancing circadian clock resetting nonspecifically.

PMID- 15147313
TI  - Dendritic spine pathology and deficits in experience-dependent dendritic
      plasticity in R6/1 Huntington's disease transgenic mice.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG
      repeat expansion coding for an expanded polyglutamine tract in the huntingtin
      protein. Dendritic abnormalities occur in human HD patients and in several
      transgenic mouse models of the disease. In this study, we examine, for the first
      time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics
      neurodegeneration seen in human HD. Enriching the environment of HD transgenic
      mice delays the onset of symptoms, so we also examine the effects of enrichment
      on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice
      reveals a decrease in dendritic spine density and dendritic spine length in
      striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a
      specific reduction in the proportion of bifurcated dendritic spines on basal
      dendrites of cortical pyramidal neurons. No differences in soma size, recurving
      distal dendrites, or dendritic branching were observed. Although home-cage
      environmental enrichment from 1 to 8 months of age increases spine density in
      wild-type mice, it has no effect on the spine pathology in HD mice. These results
      show that dendritic spine pathology in R6/1 HD mice resembles degenerative
      changes seen in human HD and in other transgenic mouse models of the disease. We
      thus provide further evidence that the HD mutation disrupts the connectivity in
      both neostriatum and cerebral cortex, which will contribute to motor and
      cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease
      pathology interferes with the normal plastic response of dendritic spines to
      environmental enrichment.

PMID- 15147312
TI  - GABAergic synapses of the suprachiasmatic nucleus exhibit a diurnal rhythm of
      short-term synaptic plasticity.
AB  - We examined synaptic plasticity at intrasuprachiasmatic nucleus (SCN) gamma
      aminobutyric acid (GABA)ergic synapses by measuring the paired-pulse ratio
      between pairs of evoked inhibitory postsynaptic currents (IPSCs). Interstimulus
      intervals were chosen to represent the range of spontaneous action potential
      firing frequencies found in SCN neurons. A majority of synapses studied during
      the day exhibited paired-pulse depression (PPD), whereas a majority of synapses
      studied during the night showed no PPD. Two types of PPD were found. Type 1 PPD
      expresses the greatest inhibition at shorter interstimulus intervals, is
      predominant in the early morning and is likely to be a result of vesicle
      depletion. Type 2 showed the greatest inhibition at interstimulus intervals
      between 175 and 225 ms, is found throughout the day yet rarely at night and is
      likely to be a result of a Ca(2+)-dependent mechanism that is independent of
      pertussis toxin-sensitive G-proteins. Thus, multiple mechanisms of synaptic
      plasticity modulate intra-SCN communication throughout the diurnal cycle.

PMID- 15147315
TI  - Substance identification by quantitative characterization of oscillatory activity
      in murine spinal cord networks on microelectrode arrays.
AB  - This paper presents a novel and comprehensive method to identify substances on
      the basis of electrical activity and is a substantial improvement for drug
      screening. The spontaneous activity of primary neuronal networks is influenced by
      neurotransmitters, ligands, and other substances in a similar fashion as known
      from in vivo pharmacology. However, quantitative methods for the identification
      of substances through their characteristic effects on network activity states
      have not yet been reported. We approached this problem by creating a database
      including native activity and five drug-induced oscillatory activity states from
      extracellular multisite recordings from microelectrode arrays. The response
      profiles consisted of 30 activity features derived from the temporal distribution
      of action potentials, integrated burst properties, calculated coefficients of
      variation, and features of Gabor fits to autocorrelograms. The different
      oscillatory states were induced by blocking neurotransmitter receptors for: (i)
      GABA(A); (ii) glycine; (iii) GABA(A) and glycine; (iv) all major synaptic types
      except AMPA, and (v) all major synapses except NMDA. To test the identification
      capability of the six substance-specific response profiles, five blind
      experiments were performed. The response features from the unknown substances
      were compared to the database using proximity measures using the normalized
      Euclidian distance to each activity state. This process created six
      identification coefficients where the smallest correctly identified the unknown
      substances. Such activity profiles are expected to become substance-specific
      'finger prints' that classify unique responses to known and unknown substances.
      It is anticipated that this kind of approach will help to quantify
      pharmacological responses of networks used as biosensors.

PMID- 15147314
TI  - Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced
      reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels.
AB  - The suprachiasmatic nucleus (SCN) of the anterior hypothalamus contains a light
      entrainable circadian pacemaker. Neurons in the SCN are part of a circuit that
      conveys light information from retinal efferents to the pineal gland. Light
      presented during the night acutely increases mRNA levels of the circadian clock
      genes Per1 and Per2 in the SCN, and acutely suppresses melatonin levels in the
      pineal gland. The present study investigated whether the ability of light to
      increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels requires
      sodium-dependent action potentials in the SCN. Per1 and Per2 mRNA levels in the
      SCN and pineal melatonin levels were measured in Syrian hamsters injected with
      tetrodotoxin (TTX) prior to light exposure or injection of N-methyl-D-aspartate
      (NMDA). TTX inhibited the ability of light to increase Per1 and Per2 mRNA levels
      and suppress pineal melatonin levels. TTX did not, however, influence the ability
      of NMDA to increase Per1 and Per2 mRNA levels, though it did inhibit the ability
      of NMDA to suppress pineal melatonin levels. These results demonstrate that
      action potentials in the SCN are not necessary for NMDA receptor activation to
      increase Per1 and Per2 mRNA levels, but are necessary for NMDA receptor
      activation to decrease pineal melatonin levels. Taken together, these data
      support the hypothesis that the mechanism through which light information is
      conveyed to the pacemaker in the SCN is separate from and independent of the
      mechanism through which light information is conveyed to the SCN cells whose
      efferents suppress pineal melatonin levels.

PMID- 15147316
TI  - Targeted introduction of V642I mutation in amyloid precursor protein gene causes
      functional abnormality resembling early stage of Alzheimer's disease in aged
      mice.
AB  - While the exact aetiology of Alzheimer's disease (AD) is unknown, distinct
      genetic mutations have been identified for the rare cases of familial AD (FAD).
      V642I mutation in amyloid precursor protein (APP) co-segregates with FAD with
      perfect penetration, and the clinicopathological characteristics of patients with
      this mutation resemble that of sporadic AD. To examine the pathogenic process of
      this FAD-linked trait in vivo, we produced a mouse with the corresponding point
      mutation in the APP gene using homologous recombination and Cre-loxP site
      specific recombination ('knock-in' technique). Mice with the heterozygous V642I
      APP allele most precisely reflected the genotype of humans bearing this mutation.
      For the observation period of 2.5 years the mutants stayed apparently
      indistinguishable from the wild-type littermates. However, behavioural analysis
      revealed significantly deteriorated long-term memory in mutants when examined for
      the retention of spatial attention. Interestingly, acquisition of spatial memory
      was slightly affected but short-term working memory was not deteriorated at all.
      Histological examination was negative for formation of neuritic plaques or
      neurofibrillary tangles, whereas the relative amount of longer form of beta
      amyloid species A beta 42(43) was significantly increased against that of the
      shorter form (A beta 40) in the mutant brain homogenates. We conclude that a
      V642I-APP mutant allele in aged mice confers functional components, but not
      organic components, of the AD-related phenotype that are observed in the early
      stage of AD. This V642I-APP knock-in mutant line may serve as a model to study
      the early pathogenic processes of AD in vivo and to develop therapeutics for this
      stage.

PMID- 15147317
TI  - Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation
      in vivo.
AB  - Mutations in the amyloid precursor protein that result in substitutions of
      glutamic acid at residue 22 of the amyloid beta protein (A beta) with glutamine
      (Q22, Dutch) or glycine (G22, Arctic) cause aggressive familial neurological
      diseases characterized by cerebrovascular haemorrhages or Alzheimer's-type
      dementia, respectively. The present study compared the ability of these peptides
      to block long-term potentiation (LTP) of glutamatergic transmission in the
      hippocampus in vivo. The effects of intracerebroventricular injection of wild
      type, Q22 and G22 A beta(1-40) peptides were examined in the CA1 area of urethane
      anaesthetized rats. Both mutant peptides were approximately 100-fold more potent
      than wild-type A beta at inhibiting LTP induced by high-frequency stimulation
      when solutions of A beta were freshly prepared. Fibrillar material, as determined
      by electron microscopy, was obvious in all these peptide solutions and exhibited
      appreciable Congo Red binding, particularly for A beta(1-40)G22 and A beta(1
      40)Q22. A soluble fraction of A beta(1-40)G22, obtained following high-speed
      centrifugation, retained full activity of the peptide solution to inhibit LTP,
      providing strong evidence that in the case of the Arctic disease a soluble
      nonfibrillar form of A beta may represent the primary mediator of A beta-related
      cognitive deficits, particularly early in the disease. In contrast, nonfibrillar
      soluble A beta(1-40)Q22 supernatant solution was approximately 10-fold less
      potent at inhibiting LTP than A beta(1-40)G22, a finding consistent with
      fibrillar A beta contributing to the inhibition of LTP by the Dutch peptide.

PMID- 15147318
TI  - Distinct properties of presynaptic group II and III metabotropic glutamate
      receptor-mediated inhibition of perforant pathway-CA1 EPSCs.
AB  - I have compared the effects of group II or III metabotropic glutamate receptor
      (mGluR) activation on monosynaptic excitatory responses recorded intracellularly
      from CA1 pyramidal neurons of rat hippocampus and evoked by perforant pathway
      stimulation in vitro. The excitatory postsynaptic currents (EPSCs) were reduced
      either by the group II mGluR agonist LY354740 (500 nM, 31 +/- 6% of control) or
      by the group III agonist L-AP4 (400 microM, 53 +/- 5% of control). Both drugs
      enhanced EPSC paired-pulse facilitation (range 125-189% of control). These
      effects were blocked by the broad-spectrum mGluR antagonist LY341495 (1 or 20
      microM) which when applied alone did not significantly change the EPSCs elicited
      at low (0.1-0.2 Hz) or higher (1-100 Hz) frequency of stimulation. Prior
      reduction of the EPSCs induced by L-AP4 did not occlude the subsequent inhibition
      elicited by LY354740. The effect of LY354740, but not that of L-AP4, was blocked
      in the presence of the cAMP analogue Sp-cAMPS (20 microM) and with the K(+)
      channel antagonist alpha-dendrotoxin (125 nM). In contrast, the effect of L-AP4,
      but not that of LY354740, was prevented by the calmodulin inhibitor ophiobolin A
      (25 microM) and with the N-type Ca(2+) channel antagonist omega-conotoxin-GVIA (1
      microM). In the presence of the P/Q type Ca(2+) channel antagonist omega-agatoxin
      IVA (400 nM), the EPSCs were depressed either by LY354740 or by L-AP4. Groups II
      and III mGluRs are segregated at the presynaptic terminal, and there are distinct
      differences between the properties of the presynaptic inhibition mediated by
      these two groups of receptors.

PMID- 15147319
TI  - Long-lasting nicotinic modulation of GABAergic synaptic transmission in the rat
      nucleus accumbens associated with behavioural sensitization to amphetamine.
AB  - A robust increase in dopaminergic transmission in the nucleus accumbens (NAc)
      shell has been reported to be consistently associated with the long-term
      expression of behavioural sensitization to drugs of abuse. However, little is
      known about how this affects the neuronal network of the NAc. We made cellular
      recordings in NAc slices of saline- and amphetamine-pretreated adult rats and
      found that expression of behavioural sensitization was associated with long
      lasting changes in the basal firing pattern of cholinergic interneurons up to 3
      weeks after the last drug injection. Consequently, upon amphetamine
      sensitization, an inhibiting effect of the nicotinic receptor blocker
      mecamylamine on the amplitudes of spontaneous GABAergic synaptic currents as well
      as on the failure rate of electrically evoked GABAergic currents was found that
      was not present under control conditions. Thus, behavioural sensitization to
      amphetamine is associated with an up-regulation of the endogenous activation of
      nicotinic receptors that, in turn, stimulate the GABAergic synaptic transmission
      within the NAc shell. This is a new mechanism by which drugs of abuse may induce
      alterations in the processing and integration of NAc inputs involved in
      psychomotor sensitization.

PMID- 15147320
TI  - The basal ganglia network mediates the planning of movement amplitude.
AB  - This study addresses the hypothesis that the basal ganglia (BG) are involved
      specifically in the planning of movement amplitude (or covariates). Although
      often advanced, based on observations that Parkinson's disease (PD) patients
      exhibit hypokinesia in the absence of significant directional errors, this
      hypothesis has been challenged by a recent alternative, that parkinsonian
      hypometria could be caused by dysfunction of on-line feedback loops. To re
      evaluate this issue, we conducted two successive experiments. In the first
      experiment we assumed that if BG are involved in extent planning then PD patients
      (who exhibit a major dysfunction within the BG network) should exhibit a
      preserved ability to use a direction precue with respect to normals, but an
      impaired ability to use an amplitude precue. Results were compatible with this
      prediction. Because this evidence did not prove conclusively that the BG is
      involved in amplitude planning (functional deficits are not restricted to the BG
      network in PD), a second experiment was conducted using positron emission
      tomography (PET). We hypothesized that if the BG is important for planning
      movement amplitude, a task requiring increased amplitude planning should produce
      increased activation in the BG network. In agreement with this prediction, we
      observed enhanced activation of BG structures under a precue condition that
      emphasized extent planning in comparison with conditions that emphasized
      direction planning or no planning. Considered together, our results are
      consistent with the idea that BG is directly involved in the planning of movement
      amplitude or of factors that covary with that parameter.

PMID- 15147321
TI  - Frequency-dependent requirement for calcium store-operated mechanisms in
      induction of homosynaptic long-term depression at hippocampus CA1 synapses.
AB  - For induction of long-term depression (LTD), mechanisms dependent on N-methyl-D
      aspartate receptors (NMDARs) and on intracellular calcium stores have been
      separately known. How these two mechanisms coexist at the same synapses is not
      clear. Here, induction of LTD at hippocampal Schaffer collateral-to-CA1 pyramidal
      cell synapses was shown to depend on NMDARs throughout the theoretically
      predicted activation range for LTD induction. With stimulation at 1 Hz, the
      largest LTD was induced in a store-independent manner. With stimulation at 0.5
      and 2.0 Hz the induced LTD was much smaller, and dependence on calcium stores
      appeared. Under caffeine application, an enlarged LTD was induced with 0.5 Hz
      stimulation. Postsynaptic blockade of ryanodine receptors prevented this caffeine
      induced enhancement of LTD. It is therefore suggested that calcium release from
      calcium stores facilitated by caffeine contributed to the LTD enhancement, and
      that the caffeine effect was exerted on the postsynaptic side. Induction of this
      enhanced LTD was resistant to NMDAR blockade. We thus propose that the store
      dependent mechanism for LTD induction is dormant at the centre of the
      theoretically predicted activation range for LTD induction, but operates at the
      fringes of this activation range, with its contribution more emphasized when
      ample calcium release occurs.

PMID- 15147322
TI  - Facilitation of visuo-motor learning by transcranial direct current stimulation
      of the motor and extrastriate visual areas in humans.
AB  - Performance of visuo-motor tasks requires the transfer of visual data to motor
      performance and depends highly on visual perception and cognitive processing,
      mainly during the learning phase. The primary aim of this study was to determine
      if the human middle temporal (MT)+/V5, an extrastriate visual area that is known
      to mediate motion processing, and the primary motor cortex are involved in
      learning of visuo-motor coordination tasks. To pursue this, we increased or
      decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex
      excitability by 10 min of anodal or cathodal transcranial direct current
      stimulation in healthy human subjects during the learning phase of a visually
      guided tracking task. The percentage of correct tracking movements increased
      significantly in the early learning phase during anodal stimulation, but only
      when the left V5 or M1 was stimulated. Cathodal stimulation had no significant
      effect. Also, stimulation of the primary visual cortex was not effective for this
      kind of task. Our data suggest that the areas V5 and M1 are involved in the early
      phase of learning of visuo-motor coordination.

PMID- 15147323
TI  - Role of the Otx1 gene in cell differentiation of mammalian cortex.
AB  - This study analyses by immunohistochemical methods the effects of the deletion of
      the Otx1 gene on 12 areas of the cerebral cortex and on neurons expressing Ca
      binding proteins (CaBP), such as parvalbumin (Pv) and calbindin-D28K (Cb). We
      found that the deletion of the Otx1 gene modified differently the various
      cortical areas. The decrease in cortical thickness ranged from 29.35 to 9.85% and
      the reduction in cellular population from 35.90 to 3.65% in the different
      cortical areas. The influence of the Otx1 gene concerns all cortical layers with
      variable effects on different cortical areas. The cellular population of cerebral
      cortex considered as a whole was reduced by 20.67%, Pv-positive (Pv+) cells by
      58.01% and Cb-positive (Cb+) cells by 51.54%. The quantitative distribution of
      Pv+ and Cb+ cells varied independently in the different cortical areas.
      Topographic analysis of CaBP cells in Otx1-null mice (Otx1(-/-)) showed that Pv+
      cells were principally distributed in layers IV and V and Cb+ cells in layers V
      and VI. Given that in the development of wild-type mice both cell types first
      appear in deep layers and later spread to superficial ones, the segregation of
      CaBP neurons in inner layers of Otx1(-/-) animals is an index of the immaturity
      of the cerebral cortex of these animals. This study showed that the Otx1 gene has
      a more complex role than previously reported, as it is involved in the maturation
      and differentiation of various cerebral cortices, and, specifically, in the
      development of CaBP cells.

PMID- 15147324
TI  - TrkA and mitogen-activated protein kinase phosphorylation are enhanced in
      sympathetic neurons lacking functional p75 neurotrophin receptor expression.
AB  - This study examined the effects of hypomorphic p75 neurotrophin receptor (p75NTR)
      expression and high levels of nerve growth factor (NGF) on trkA phosphorylation
      and downstream activation of p44/42 mitogen-activated protein kinase (MAPK). Post
      ganglionic sympathetic neurons from postnatal day 1 p75NTR exon III null mutant
      (p75(-/-)) and 129/SvJ mice were cultured in the presence of 50 ng/mL NGF and
      analysed by Western blotting. Levels of phosphorylated trkA are increased in p75(
      /-) neurons compared with 129/SvJ neurons, and these higher levels are maintained
      with continuous exposure to NGF. MAPK is also phosphorylated to a greater extent
      in p75(-/-) neurons than in 129/SvJ neurons, both within 10 min of exposure to
      NGF, and with continuous NGF treatment for 5 days. These data provide new insight
      into the mechanism underlying enhanced neurite outgrowth in p75(-/-) neurons,
      demonstrating that trkA and MAPK signalling in sympathetic neurons are increased
      when p75NTR function is disrupted.

PMID- 15147325
TI  - Thapsigargin-induced mobilization of dendritic dense-cored vesicles in rat
      supraoptic neurons.
AB  - Dense-cored vesicles (DCVs) containing oxytocin or vasopressin are secreted from
      both the nerve terminals in the posterior pituitary and dendrites in the
      hypothalamus of magnocellular supraoptic neurons. Dendritic secretion can be
      enhanced (primed) by pretreatment with either thapsigargin or oxytocin for
      subsequent activity-dependent release. Here, we determined whether priming
      involves a translocation of DCV closer to the dendritic membrane. To reduce total
      vesicle content, rats were salt-loaded for 24 h before application of
      thapsigargin or vehicle onto the ventrally exposed surface of the supraoptic
      nucleus in vivo. Tissues were then prepared for quantitative electron microscopic
      analysis of the total incidence of DCVs within supraoptic dendritic cross
      sections, and of the incidence and distance (within a 500-nm margin) of each DCV
      to the dendritic plasma membrane. Salt loading per se did not alter the frequency
      distribution or average proportion of DCVs found in the 500-nm margin but
      significantly decreased the average incidence of DCVs per dendrite by 30% (P <
      0.05). However, thapsigargin treatment resulted in a significant increase in the
      total incidence of DCVs within the 500-nm margins and a higher incidence of DCVs
      within the first 200 nm of the plasma membrane (P < 0.05), indicating that the
      thapsigargin-induced priming involves a relocation of DCVs closer to sites of
      secretion.

PMID- 15147328
TI  - Reactive oxygen species induce RNA damage in human atherosclerosis.
AB  - BACKGROUND: Reactive oxygen species (ROS)-induced DNA damage has recently been
      identified in both human and experimental atherosclerosis. This study was
      undertaken to investigate whether RNA damage occurs in human atherosclerotic
      plaques and whether this could be related to oxidative stress. MATERIALS AND
      METHODS: The integrity of total RNA isolated from carotid endarterectomy
      specimens (n = 20) and nonatherosclerotic mammary arteries (n = 20) was analyzed
      using an Agilent 2100 Bioanalyser (Agilent Technologies, Palo Alto, CA).
      Oxidative modifications of RNA were detected by immunohistochemistry. RESULTS:
      Eleven out of 20 atherosclerotic plaques showed a significant reduction of the
      18S/28S rRNA peaks and a shift in the RNA electropherogram to shorter fragment
      sizes. In contrast, all mammary arteries showed good-quality RNA with clear 18S
      and 28S rRNA peaks. Strong nuclear and cytoplasmic immunoreactivity for oxidative
      damage marker 7,8-dihydro-8-oxo-2'-guanosine (8-oxoG) could be detected in the
      entire plaque in smooth muscle cells (SMCs), macrophages and endothelial cells,
      but not in SMCs of adjacent normal media or in mammary arteries. Cytoplasmic 8
      oxoG staining in the plaque clearly diminished when tissue sections were
      pretreated with RNase A, suggesting oxidative base damage of RNA. In vitro
      treatment of total RNA with ROS-releasing compounds induced RNA degradation.
      CONCLUSION: Both loss of RNA integrity and 8-oxoG oxidative modifications were
      found in human atherosclerotic plaques. Because RNA damage may affect in vitro
      transcript quantification, RT-PCR results must be interpreted cautiously if
      independent experimental validation (e.g. evaluation of RNA integrity) is
      lacking.

PMID- 15147329
TI  - Role of Toll-like receptor 4 in the initiation and progression of atherosclerotic
      disease.
AB  - The family of Toll-like receptors (TLRs) initiates an innate immune response
      after recognition of pathogen-associated molecular patterns (PAMPs). Evidence is
      accumulating that TLRs, and particularly TLR4, are important players in the
      initiation and progression of atherosclerotic disease. Not only exogenous ligands
      but also endogenous ligands that are expressed during arterial injury are
      recognized by TLR4. Mouse knockout studies and epidemiological studies of human
      TLR4 polymorphisms have demonstrated that the TLR4 might play a role in the
      initiation and progression of atherosclerosis. This review will summarize the
      latest progression in research on the role of TLR4 in arterial occlusive disease
      In addition, the potential of intervention in TLR4 signalling to influence
      progression of atherosclerotic disease is discussed.

PMID- 15147330
TI  - Low-grade systemic inflammation impairs arterial stiffness in newly diagnosed
      hypercholesterolaemia.
AB  - BACKGROUND: Excess of cardiovascular risk among patients with chronic
      inflammatory diseases has been attributed to increased arterial stiffness.
      Hypercholesterolaemia has been demonstrated to promote a low-grade inflammatory
      status. The objective of the present study was to define, in
      hypercholesterolaemia, the influence of plasma lipids, low-grade inflammation,
      and indices of adiposity on aortic pulse wave velocity, a measure of arterial
      stiffness and cardiovascular risk. MATERIALS AND METHODS: Anthropometric
      characteristics, plasma lipids, C-reactive protein and aortic pulse wave velocity
      were measured in 85 subjects (60 patients with newly diagnosed never-treated
      hypercholesterolaemia and 25 age- and sex-matched normocholesterolaemic
      controls). RESULTS: Plasma C-reactive protein and aortic pulse wave velocity were
      significantly higher among hypercholesterolaemic patients than in controls (P <
      0.05 for both). Aortic pulse wave velocity was associated with age (r = 0.24, P =
      0.04), body mass index (r = 0.33, P = 0.006), waist (r = 0.42, P < 0.001) and hip
      (r = 0.32, P = 0.007) circumferences, as well as with systolic (r = 0.34, P =
      0.003) and diastolic (r = 0.30, P = 0.01) blood pressures, plasma C-reactive
      protein (r = 0.51, P < 0.001), total cholesterol (r = 0.45, P < 0.001), and low
      density lipoprotein cholesterol (r = 0.46, P < 0.001). In the multivariate
      analysis, waist circumference and C-reactive protein levels predicted increased
      aortic stiffness, independently of traditional cardiovascular risk factors. The
      degree of independent association between cholesterol, systolic blood pressure
      and aortic stiffness increased when indices of adiposity and inflammation were
      excluded from the multivariate analysis. Comparable results were obtained when
      the analyses were restricted to hypercholesterolaemic patients. CONCLUSIONS: Low
      grade systemic inflammation and abdominal fat, more than traditional risk
      factors, are major determinants of reduced arterial distensibility in
      hypercholesterolaemia.

PMID- 15147331
TI  - Natriuretic peptides as markers of preclinical cardiac disease in obesity.
AB  - BACKGROUND: Aim of the study was to evaluate the role of atrial (ANP) and brain
      natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.
      METHODS: We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24
      h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25
      lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent
      measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP)
      monitoring, digitized M-mode and Doppler echocardiography. RESULTS: Mean values
      of ANP and BNP were similar among the three groups. All the subjects had normal
      left ventricular (LV) systolic function. Within each group ANP levels were higher
      in patients with LV diastolic dysfunction than in patients with normal diastolic
      function, and BNP levels were higher in patients with LV hypertrophy and in
      patients with LV diastolic dysfunction. Within each group, ANP levels were
      inversely correlated with LV diastolic indices, whereas BNP levels were directly
      correlated with LV mass index and inversely correlated with LV diastolic indices.
      ANP and BNP levels were not correlated with other echocardiographic parameters,
      age, BMI or 24-h BP values. CONCLUSION: In normotensive and hypertensive obese
      subjects the relationships of ANP and BNP levels with LV morpho-functional
      characteristics follow the same trend as in lean hypertensives, with ANP mainly
      influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and
      LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers
      of preclinical cardiac disease in obesity.

PMID- 15147332
TI  - Sex hormone regulation of systemic endothelial and renal microvascular reactivity
      in type-2 diabetes: studies in gonadectomized and sham-operated Zucker diabetic
      rats.
AB  - BACKGROUND: Male Zucker diabetic rats exhibit a more severe endotheliopathy in
      comparison with their female diabetic litter mates. The plasma concentrations of
      both thromboxanes and endothelins are elevated in diabetes, and the receptor
      cross-talk between TXA(2) and ET-1 receptors may be enhanced in type-2 diabetic
      Zucker rats. AIMS: To determine the role of the endogenous sex steroid hormones,
      testosterone and estradiol on the systemic and renal microvascular reactivity to
      ET-1, thromboxane-mimetic U46619, ET-TXA(2) receptor interaction, and the nitric
      oxide vasodilator system in Zucker hypertensive-diabetic rats. METHODS: Male and
      female Zucker rats aged 8-10 weeks were each divided into two groups. The male
      rats were castrated or underwent a sham operation. The female rats were spayed
      (bilateral ovariectomy and hysterectomy) or had a sham operation. All rats were
      studied 4-6 weeks after the gonadectomy or sham operations. Blood glucose and
      insulin as well as plasma concentrations of testosterone and estradiol were
      determined. Haemodynamic studies were undertaken with determination of the dose
      response curve for mean arterial pressure (MAP), renal cortical flow (RCF) and
      renal medullary blood flow (MBF) in response to ET-1 and U46619, and the effect
      of interdiction of the ET-TXA(2) interaction with ET-antagonists BQ610 and BQ788.
      The role of endogenous NO was assessed by its response to graded acetylcholine
      doses and to a L-NG-nitro-arginine methyl ester (L-NAME) infusion. RESULTS:
      Castrated male rats had a significantly lower blood glucose concentration (295 +/
      33 mg dL(-1)) compared with their sham-controls (481 +/- 40 mg dL(-1)), P =
      0.008. Mean arterial pressure tended to be lower in the castrated rats.
      Gonadectomy reduced the plasma testosterone and estradiol concentrations.
      Castration abolished the hypotensive action of U46619 compared with sham-operated
      male rats (P < 0.0001, anova). Conversely, the pressor action of U46619 seen in
      the sham-operated female rats was reversed to a profound hypotensive action in
      the spayed rats (P < 0.001, anova). The change in MAP after U46619 was inversely
      correlated to the plasma testosterone concentration (r = -0.73, P = 0.027). The
      paradoxical hypotensive response elicited by ET-1 in the Zucker diabetic rats of
      both sexes was abolished by castration only (P < 0.005, anova). Castration caused
      a significant (P = 0.011) augmentation of the vasodilator response to
      acetylcholine, while spaying caused a slight attenuation. Castration, but not
      spaying, resulted in significant increases in MBF after U46619 (P = 0.003,
      anova), ET-1 (P = 0.005, anova) and acetylcholine (P = 0.053, anova). The ET-(B)
      antagonist BQ788 augmented the U46619-induced rise in MAP in castrated male rats,
      and also abolished the U46619-induced increase in MBF (P < 0.01 anova). L-NAME
      (25 mg kg(-1)) increased MAP and decreased MBF in the gonadectomized and sham
      operated rats, except for the castrated male Zucker rats, where it significantly
      increased MBF (+90 +/- 31 PU) (P = 0.0004, anova) despite the increase in MAP.
      CONCLUSIONS: Testosterone and estradiol regulate systemic and microvascular
      reactivity to TXA(2) receptor stimulation in type-2 diabetic Zucker rats. The
      impact of testosterone on blood glucose concentration, blood pressure, and the
      systemic and renal microcirculatory response to ET-1 and NO, as well as the
      endothelin-thromboxane receptor cross talk, is greater, and opposite to that of
      estradiol. The effects of testosterone withdrawal may at least in part be
      mediated by the ET-B receptor subtype and NO generation. Androgen blockade should
      be investigated further for the reversal or delay of hypertensive-diabetic
      endotheliopathy.

PMID- 15147333
TI  - Increasing neutrophil F-actin corrects CD11b exposure in Type 2 diabetes.
AB  - BACKGROUND: Leukocyte dysfunction contributes to the pathogenesis of diabetic
      vascular complications. Neutrophils adhere to the endothelium through the
      beta(2)integrin CD11b/CD18. In Type 2 diabetes, neutrophil surface CD11b
      expression is increased and is associated with impaired actin polymerization.
      This study aimed to determine whether increasing neutrophil actin polymerization
      could correct the defect in CD11b exposure. DESIGN: Neutrophil actin
      polymerization was stimulated with the tyrosine phosphatase inhibitor
      phenylarsine oxide (PAO), and cytoskeletal phosphotyrosine was monitored by
      immunoblotting Triton X-100 insoluble fractions of cells. Neutrophil F-actin was
      measured with phalloidin-FITC staining, and surface CD11b expression was
      determined with anti-CD11b-PE before analysis with flow cytometry. RESULTS:
      Phenylarsine oxide caused an increase in phosphotyrosine in neutrophils from both
      patients with Type 2 diabetes (DM) and controls (NC) (-fold increase: NC, 1.43 +/
      0.16; DM, 1.46 +/- 0.10). The response to PAO in terms of phalloidin-binding was
      impaired in neutrophils from patients [phalloidin-FITC MFI area under the curve,
      NC 200 +/- 5 (x 10(3)), DM 124 +/- 9 (x 10(3)), P < 0.0001]. Phenylarsine oxide
      at concentrations < 10 micro mol L(-1) also caused loss of CD11b from neutrophil
      surfaces that was impaired in samples from patients [CD11b sites area under the
      curve NC 90 +/- 6 (x 10(3)), DM 121 +/- 9 (x 10(3)), P < 0.002]. However, in
      neutrophils from patients, incubation with PAO at a concentration of > 10 micro
      mol L(-1) caused a significant increase in intracellular F-actin and CD11b down
      regulation equivalent to that observed in controls. CONCLUSION: In Type 2
      diabetes, impaired neutrophil actin polymerization even in response to increasing
      cytoskeletal phophotyrosine suggests a downstream defect. Furthermore, increasing
      actin polymerization, above a minimum threshold level, corrects the defect in
      integrin exposure. Correction of the actin polymerization defect in Type 2
      diabetes could improve the prognosis of diabetic vascular complications.

PMID- 15147334
TI  - Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic
      iodine uptake level and post-therapeutic outcome.
AB  - BACKGROUND: High iodine uptake levels are widely accepted as a condition for
      successful treatment with radioiodine (RAI). However, the existing data are
      controversial and the correlation of pretherapeutic RAI uptake level and outcome
      of RAI therapy has not yet been quantified. The aim of this study was to analyze
      the influence of RAI uptake on the outcome after RAI treatment and to estimate
      uptake-dependent success rates. MATERIALS AND METHODS: We retrospectively
      analyzed 229 patients (m = 53, f = 176; age 64 +/- 14 years) suffering from toxic
      adenoma, multinodular goitre or Graves' disease, respectively. Clinical status
      and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment.
      Successful treatment was defined as loss of hyperthyroidism 18 months after
      radioiodine therapy. Logistic regression was used to assess the relation between
      the maximum iodine uptake and the rate of success and hypothyroidism,
      respectively, after RAI treatment. RESULTS: Overall, patients presented with
      pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI
      treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism
      occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The
      patients with the lowest pretherapeutic RAI uptakes showed the highest success
      rates. The overall success rate significantly decreased from 92% at low RAI
      uptakes to 57% at high uptakes (P = 0.002). This effect was found in the patients
      suffering from multinodular goitre as well as in the patients with Graves'
      disease. CONCLUSION: In contrast to the current opinion, our results provide
      evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome
      are inversely correlated.

PMID- 15147336
TI  - Increased red blood cell adhesiveness/aggregation owing to fibrinogen elevation
      in hypercholesterolaemic patients and the rationale of fibrinogen-lowering by LDL
      apheresis.

PMID- 15147335
TI  - Basal and exercise-induced sympathetic nervous activity and lipolysis in adipose
      tissue of patients with anorexia nervosa.
AB  - BACKGROUND: The sympathetic nervous system plays an important role in the
      regulation of adipose tissue (AT) lipolysis, which is a key step in the metabolic
      processes leading to the decrease of fat mass. The present study was designed to
      determine in vivo basal and exercise-stimulated lipolysis and concentrations of
      catecholamines, the major hormones controlling lipolysis, in subcutaneous
      abdominal AT in patients with anorexia nervosa (AN), characterized by self
      induced starvation and excessive exercises resulting in severe malnutrition and
      fat store loss. The results of local catecholamines and glycerol levels were
      compared with those in plasma in both experimental groups. MATERIAL AND METHODS:
      An in vivo microdialysis technique was used for the assessment of norepinephrine,
      dihydroxyphenylalanine, dihydroxyphenylacetic acid and glycerol concentrations in
      subcutaneous AT of 10 women with AN (body mass index: 15.57 +/- 0.55 kg m(-2))
      and 10 age-matched controls (body mass index: 21.56 +/- 0.41 kg m(-2)). Both the
      AN patients and the control subjects underwent a 1.5 W kg(-1) exercise test.
      RESULTS: Basal AT norepinephrine concentrations were increased in the AN patients
      in comparison with the controls. Basal AT glycerol concentrations were similar in
      both groups. During exercise, a local increase in the AT norepinephrine and
      glycerol concentrations was observed in the AN patients only. In contrast to the
      controls, the basal AT dihydroxyphenylalanine and dihydroxyphenylacetic acid
      levels in the AN patients were high and remained unchanged during exercise. Basal
      and exercise-stimulated plasma norepinephrine, dihydroxyphenylalanine,
      dihydroxyphenylacetic acid and glycerol levels were not different in the AN
      patients and healthy controls. CONCLUSION: Our study provides evidence of
      elevated baseline and exercise-induced sympathetic nervous activity and exercise
      induced lipolysis in abdominal AT of AN patients.

PMID- 15147338
TI  - Lymphopenia and neutrophilia in SARS are related to the prevailing serum
      cortisol.

PMID- 15147340
TI  - Interleukin-18 as a potential target in inflammatory arthritis.

PMID- 15147339
TI  - Antiphospholipid syndrome: multiple mechanisms.

PMID- 15147341
TI  - Effects of commonly used immunosuppressants on graft-derived fibroblasts.
AB  - In acute rejection of transplanted organs intragraft fibroblasts increase their
      production of hyaluronan. Hyaluronan has strong water binding capacity and an
      increased tissue content of hyaluronan thus contributes to the development of
      interstitial oedema. The present study examined the effects of commonly used
      immunosuppressants (prednisolone, cyclosporin, tacrolimus, mycophenolic acid and
      sirolimus) on fibroblast proliferation, hyaluronan production and cell surface
      receptor expression. Fibroblasts isolated from rejecting tissue and from normal,
      non-transplanted tissue were studied in parallel. All substances investigated,
      except tacrolimus, were found to affect fibroblasts in one way or another. The
      most striking effect was the almost total inhibition of fibroblast proliferation
      in the presence of mycophenolic acid. Cyclosporin reduced the proliferation by
      about 50% and prednisolone had an inhibiting effect on hyaluronan production (50%
      reduction). These effects were observed on fibroblasts isolated from rat cardiac
      allografts undergoing rejection as well as on fibroblasts obtained from normal
      heart tissue. In contrast, sirolimus was found to stimulate the proliferation of
      fibroblasts from rejecting tissue (100% increase), but not that of normal
      fibroblasts. The majority of the fibroblasts expressed the hyaluronan receptor
      CD44, with a more intense expression in cultures of fibroblasts derived at
      rejection. None of the immunosuppressants affected the staining pattern (number
      of positive cells or intensity). The inhibitory effects of prednisolone,
      cyclosporin and mycophenolic acid on fibroblasts may contribute to the overall
      beneficial effects of these drugs when used for prevention or treatment of
      rejection.

PMID- 15147342
TI  - Induction of hyperthyroidism in mice by intradermal immunization with DNA
      encoding the thyrotropin receptor.
AB  - Intramuscular injection with plasmid DNA encoding the human thyrotropin receptor
      (TSHR) has been known to elicit symptoms of Graves' disease (GD) in outbred but
      not inbred mice. In this study, we have examined, firstly, whether intradermal
      (i.d.) injection of TSHR DNA can induce hyperthyroidism in BALB/c mice and,
      secondly, whether coinjection of TSHR- and cytokine-producing plasmids can
      influence the outcome of disease. Animals were i.d. challenged at 0, 3 and 6
      weeks with TSHR DNA and the immune response was assessed at the end of the 8th or
      10th week. In two experiments, a total of 10 (67%) of 15 mice developed TSHR
      specific antibodies as assessed by flow cytometry. Of these, 4 (27%) mice had
      elevated thyroxine (TT4) levels and goitrous thyroids with activated follicular
      epithelial cells but no evidence of lymphocytic infiltration. At 10 weeks,
      thyroid-stimulating antibodies (TSAb) were detected in two out of the four
      hyperthyroid animals. Interestingly, in mice that received a coinjection of TSHR-
      and IL-2- or IL-4-producing plasmids, there was no production of TSAbs and no
      evidence of hyperthyroidism. On the other hand, coinjection of DNA plasmids
      encoding TSHR and IL-12 did not significantly enhance GD development since two
      out of seven animals became thyrotoxic, but had no goitre. These results
      demonstrate that i.d. delivery of human TSHR DNA can break tolerance and elicit
      GD in inbred mice. The data do not support the notion that TSAb production is Th2
      dependent in murine GD but they also suggest that codelivery of TSHR and Th1
      promoting IL-12 genes may not be sufficient to enhance disease incidence and/or
      severity in this model.

PMID- 15147343
TI  - A novel and effective approach of developing aggressive experimental autoimmune
      gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic
      acid.
AB  - Neonatal thymectomy induces autoimmune gastritis (AIG) in 40-70% of BALB/c mice.
      We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid
      (poly I:C) might allow development of a more aggressive model of AIG. A group of
      BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice
      were either injected with poly I:C or phosphate-buffered saline (PBS). Non
      thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal
      thymectomized mice injected with poly I:C developed 3 cardinal features of AIG:
      (1) moderate to severe degree gastritis (2) presence of autoantibody to H(+)/K(+)
      ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated
      neonatal thymectomized BALB/c mice developed some, but not, all features of AIG.
      A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice
      administered with only poly I:C. Administration of poly I:C in neonatal
      thymectomized BALB/c mice in the first and second week appeared to be the most
      effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL
      12p70, interferon-gamma and tumour necrosis factor-alpha were significantly
      higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal
      thymectomized mice (P < 0.05). The frequencies of CD4(+)CD25(+) regulatory T
      cells in the spleen were significantly decreased in neonatal thymectomized mice
      administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P
      < 0.01). Taken together, these results suggest that induction of inflammatory
      cytokines and reduction of regulatory T cells by poly I:C might contribute to the
      development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.

PMID- 15147344
TI  - Fucoidan derived from Cladosiphon okamuranus Tokida ameliorates murine chronic
      colitis through the down-regulation of interleukin-6 production on colonic
      epithelial cells.
AB  - Our previous study indicated that the interleukin (IL)-6/STAT-3 signal was up
      regulated in inflammatory bowel disease (IBD) in both humans and animal models.
      We also discovered phosphorylated STAT-3 in the nucleus of the colonic epithelial
      cells in IBD mice. Intestinal epithelial cells (IEC) have been shown to secrete
      IL-6. Therefore, the secretion of IL-6 from IEC may be one of the mechanisms of
      STAT-3 phosphorylation in IEC during the pathogenesis of IBD, and inhibition of
      IL-6 production by IEC may be beneficial in preventing IBD. We examined the
      preventative effect of various types of fucoidans on IL-6 production in a
      lipopolysaccharide (LPS)-stimulated murine colonic epithelial cells line, CMT-93,
      in vitro. We also determined in vivo the effect of fucoidans on murine chronic
      colitis induced with dextran sodium sulphate. Among fucoidans, those from
      Cladosiphon okamuranus Tokida and Kjellmaniella crassifolia inhibited IL-6
      production in CMT-93 cells with the down-regulation of NF-kappaB nuclear
      translocation. Analysis of the effect of fucoidan on murine colitis in vivo
      showed that the disease activity index and myeloperoxidase activity decreased in
      mice fed Cladosiphon fucoidan, but not Fucus fucoidan. Cytokine profiles in
      colonic lamina propria indicated that the synthesis of interferon (IFN)-gamma and
      IL-6 decreased and that of IL-10 and transforming growth factor (TGF)-beta
      increased in mice fed Cladosiphon fucoidan, compared with mice fed a standard
      diet or Fucus fucoidan. The levels of IL-6 mRNA in colonic epithelial cells was
      lower in colitis-induced Balb/c mice fed Cladosiphon fucoidan than those fed a
      standard diet. Fucoidan improves murine chronic colitis by down-regulating the
      synthesis of IL-6 in the colonic epithelial cells. Fucoidan derived from C. o.
      Tokida may be useful as a dietary substance for the patients with inflammatory
      bowel disease.

PMID- 15147345
TI  - The roles of interleukin-18 in collagen-induced arthritis in the BB rat.
AB  - Interleukin (IL)-18 is a member of the IL-1 cytokine family. Its expression is
      increased in rheumatoid arthritis synovium, and its proinflammatory effects have
      been demonstrated in experimental models of murine arthritis. Here, we
      investigate the actions of varying doses of recombinant rat IL-18 (rIL-18) on the
      course of type II collagen-induced arthritis (CIA) in BB rats, including clinical
      and immune events, plus splenic cytokine production. Small doses of rIL-18 (10
      and 50 microg/rat) administered intraperitoneally (i.p.) increased arthritis
      incidence and severity (P < 0.01) when a low-potency CII preparation was used for
      immunization. IgG1 and IgG2a anti-CII antibody levels were significantly greater
      in rats given 10 and 50 microg rIL-18 doses than controls. rIL-18 significantly
      increased levels of proinflammatory cytokines [interferon (IFN)-gamma, IL-2,
      tumour necrosis factor (TNF)-alpha and IL-6] produced by splenocyte cultures.
      Larger doses of rIL-18 (300 microg/rat) suppressed arthritis and immunity. To
      ascertain whether the pro-arthritic effects of IL-18 could be attenuated, rats
      were treated with neutralizing rabbit anti-rIL-18 IgG before immunization with a
      high-potency CII preparation. When given serially for 3 weeks, the incidence and
      severity of CIA, in addition to anti-CII IgG2a and splenic IL-6 and IFN-gamma
      production, were all significantly reduced. Similar results were noted when
      antibody was given twice, just before arthritis onset. These results demonstrate
      that IL-18 plays an important proinflammatory role in the pathogenesis of CIA
      which is achieved, in part, by an immunostimulatory action. Neutralizing
      endogenous IL-18 with antibodies attenuated CIA, CII immunity and cytokine
      responses. These studies support the use of IL-18 antagonists as treatments for
      inflammatory arthritis.

PMID- 15147346
TI  - Identification of systemically expanded activated T cell clones in MRL/lpr and
      NZB/W F1 lupus model mice.
AB  - CD4(+) T lymphocytes play an important role in the pathogenesis of systemic lupus
      erythematosus (SLE). To characterize the clonal expansion of CD4(+) T cells in
      murine lupus models, we analysed the T cell clonality in various organs of young
      and nephritic MRL/lpr and NZB/W F1 mice using reverse transcription-polymerase
      chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism
      (SSCP) analysis. We demonstrated that some identical T cell clonotypes expanded
      and accumulated in different organs (the bilateral kidneys, brain, lung and
      intestine) in nephritic diseased mice, and that a number of these identical
      clonotypes were CD4(+) T cells. In contrast, young mice exhibited little
      accumulation of common clones in different organs. The T cell receptor (TCR) V
      beta usage of these identical clonotypes was limited to V beta 2, 6, 8.1, 10, 16
      and 18 in MRL/lpr mice and to V beta 6 and 7 in NZB/W F1 mice. Furthermore, some
      conserved amino acid motifs such as I, D or E and G were observed in CDR3 loops
      of TCR beta chains from these identical CD4(+) clonotypes. The existence of
      systemically expanding CD4(+) T cell clones in the central nervous system (CNS)
      suggests the involvement of the systemic autoimmunity in CNS lesions of lupus.
      FACS-sorted CD4(+)CD69(+) cells from the kidney displayed expanded clonotypes
      identical to those obtained from the whole kidney and other organs from the same
      individual. These findings suggest that activated and clonally expanded CD4(+) T
      cells accumulate in different tissues of nephritic lupus mice, and these
      clonotypes might recognize restricted T cell epitopes on autoantigens involved in
      specific immune responses of SLE, thus playing a pathogenic role in these lupus
      mice.

PMID- 15147347
TI  - Constitutive expression of interleukin-18 and interleukin-18 receptor mRNA in
      tumour derived human B-cell lines.
AB  - Interleukin-18 (IL-18) is a pro-inflammatory cytokine involved in the Th1 immune
      response and expressed by a variety of cell types. IL-18 is a member of the IL-1
      family and plays an important role in autoimmune diseases and inflammation. Using
      reverse transcriptase-polymerase chain reaction (RT-PCR) mRNA expression of IL
      18, IL-18 receptor alpha (IL-18R alpha), and beta (IL-18R beta) were studied in
      tumour derived human B-cell lines. Furthermore, we investigated IL-18 protein
      secretion by using enzyme linked immunosorbent assay (ELISA). The results, as
      presented in this report, suggest that IL-18, IL-18R alpha, and IL-18R beta mRNA
      are constitutively and ubiquitously expressed in human B-cell lines, but
      secretion of the functional protein does not occur. We therefore speculate that
      IL-18 possibly affects B-cells through paracrine actions.

PMID- 15147348
TI  - Differential expression of CTLA-4 among T cell subsets.
AB  - CTLA-4 (CD152), the CD28 homologue, is a costimulatory molecule with negative
      effects on T cell activation. In addition to its role in the termination of
      activation, CTLA-4 has been implicated in anergy induction and the function of
      regulatory cells. As an intracellular molecule, it must first relocate to the
      cell surface and be ligated, in order to inhibit activation. Although some
      studies have investigated CTLA-4 expression on CD4(+) T cells, evidence is
      lacking regarding the kinetics of expression, and expression on T cell
      subpopulations. We have investigated CTLA-4 kinetics on human purified peripheral
      CD4(+), naive, memory, CD4(+)CD25(-), CD4(+)CD25(+) regulatory T cells, and T
      cell clones. Intracellular stores of CTLA-4 were shown to be very low in naive T
      cells, whilst significant amounts were present in memory T cells and T cell
      clones. Cell surface CTLA-4 expression was then investigated on CD4(+)CD45RA(+)
      (naive), CD4(+)CD45RO(+) (memory), CD4(+)CD25(-), and CD4(+)CD25(+) T cells. CD25
      and CD45RO are both expressed by regulatory T cells. On naive and CD4(+)CD25(-) T
      cells, CTLA-4 expression declined after four hours. In contrast, on memory and
      CD4(+)CD25(+) T cells, high levels of expression were maintained until at least
      48 hours. In addition, significant CTLA-4 expression was observed on T cell
      clones following anergy induction, indicating the potential involvement of CTLA-4
      also in this form of tolerance.

PMID- 15147349
TI  - Recognition of nonpeptide antigens by human V gamma 9V delta 2 T cells requires
      contact with cells of human origin.
AB  - SUMMARY It is becoming apparent that gamma delta T cells form an important part
      of the adaptive immune response. However, the ligands recognized by gamma delta T
      cell receptors (TCRs) and the exact biological function of the cells that express
      this receptor remain unclear. Numerous studies have shown that the dominant human
      peripheral blood subset of gamma delta T cells, which express a V gamma 9V delta
      2 TCR, can activate in response to low molecular weight nonpeptidic molecules.
      Some of these components have been purified from bacteria or parasites. We
      examined the activation of polyclonal gamma delta T cell lines, clones with V
      gamma 9V delta 2 and V gamma 9V delta 1 TCRs, and gamma delta T cells directly ex
      vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP)
      antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). V
      gamma 9V delta 2 T cells were able to respond to multiple small organic molecules
      of highly variable structure whereas cells expressing a similar V gamma 9 chain
      paired with a V delta 1 chain failed to recognize these antigens. Thus, the TCR
      delta chain appears to make an important contribution to the recognition of these
      antigens. The kinetics of responses to alkylphosphate and alkylamine antigens
      differ from those of responses to the nBP pamidronate. These different classes of
      antigen are believed to have differed mechanisms of action. Such differences
      explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still
      retain their ability to activate gamma delta T cells while alkylphosphate and
      alkylamine antigens cannot. We also demonstrate that a substantial proportion of
      the cells that produce IFN gamma directly ex vivo in response to PPD are gamma
      delta T cells and that gamma delta T cell activation requires contact with cells
      of human origin.

PMID- 15147350
TI  - Langerhans cells from human oral epithelium are more effective at stimulating
      allogeneic T cells in vitro than Langerhans cells from skin.
AB  - This report is focused on the functional capacity of Langerhans cells (LC) in the
      epithelium of skin and oral mucosa, which both meet different antigenic
      challenges. The capacity of LC from human oral and skin epithelium to provide co
      stimulatory signals to T cells in vitro was compared. LC in a crude suspension of
      oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity
      compared to skin epithelial cells. This applied both to cultures with
      concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial
      cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory
      capacity of oral and skin epithelial cells was reduced by >70% if monoclonal
      antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic
      T cells, indicating the involvement of HLA class II expressing LC.
      Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in
      sections from both oral and skin epithelium. Interleukin (IL)-8 production was
      higher in cultures of oral epithelial cells and con-A stimulated T cells than in
      corresponding cultures with skin epithelial cells as accessory cells. The results
      suggest that LC in human oral epithelium are more efficient at stimulating T
      cells than those of skin.

PMID- 15147351
TI  - Differential gene expression in mononuclear phagocytes infected with pathogenic
      and non-pathogenic mycobacteria.
AB  - The pathogenic mycobacteria are an insidious group of bacterial pathogens that
      cause the deaths of millions of people every year. One of the reasons these
      pathogens are so successful is that they are able to invade and replicate within
      host macrophages, one of the first lines of defence against intruding pathogens.
      In contrast, non-pathogenic mycobacteria, such as Mycobacterium smegmatis are
      killed rapidly by macrophages. In order to understand better the series of events
      that allow pathogenic mycobacteria to survive and replicate within macrophages,
      while the non-pathogenic mycobacteria are killed rapidly, we inoculated the human
      monocytic cell line U937 with pathogenic (M. tuberculosis and M. avium) and non
      pathogenic (M. smegmatis) mycobacteria and monitored the expression of over 3500
      genes at 4, 12 and 24 h post-inoculation using a commercially available gene
      array system. We observed multiple differences in the gene expression patterns of
      monocytes infected with pathogenic and non-pathogenic mycobacteria including
      genes involved in cytokine, lymphokine and chemokine production, adhesion,
      apoptosis, signal transduction, transcription, protein cleavage, actin
      polymerization and growth. We also observed differences in gene expression
      profiles in monocytes infected with M. tuberculosis or M. avium, indicating that
      there are differences in the host pathogen interactions of mononuclear phagocytes
      infected with different pathogenic mycobacterial species. These results increase
      the understanding of the mechanisms used by pathogenic mycobacteria to cause
      disease, the host response to these organisms, and provide new insights for
      antimycobacterial intervention strategies.

PMID- 15147352
TI  - Thymic volume is associated independently with the magnitude of short- and long
      term repopulation of CD4+ T cells in HIV-infected adults after highly active
      antiretroviral therapy (HAART).
AB  - Age is one of the main factors involved in the rapidity and the magnitude of
      CD4(+) T cell repopulation in human immunodeficiency virus (HIV)-infected
      patients on highly active antiretroviral treatment (HAART). Improved thymic
      function has been suggested as the main factor associated with CD4(+) T cell
      restoration after HAART. This work was undertaken to determine, among host
      factors, the predictor variable at baseline involved in the magnitude of short-
      and long-term recovery of CD4(+) T cells after HAART. HIV-RNA levels and CD4(+) T
      cell numbers were determined in 54 HIV-infected adults at baseline and at weeks
      4, 12, 48 and 96 after HAART. T cell subpopulations were determined by flow
      cytometry, thymic volume by computed tomography, T cell receptor excision circle
      (TREC)-bearing cells by quantitative polymerase chian reaction (PCR) and
      interleukin (IL)-7 levels by enzyme linked immunosorbent assay at baseline. The
      phenotype of patients' isolates was determined by infecting GHOST cells
      expressing CCR5 and CXCR4. The possible interference of phenotype with thymic
      function was also analysed. Baseline thymic volume was associated independently
      with the magnitude of short- and long-term recovery of CD4(+) T cells after
      HAART, despite the patients' viral phenotype. The measurement of thymic volume
      before therapy may predict the magnitude of T cell increase. This result could
      have important clinical implications not only in HIV-infected patients, but also
      in other scenarios of T cell depletion such as bone marrow transplantation and
      chemotherapy.

PMID- 15147353
TI  - Kinetics of soluble tumour necrosis factor (TNF)-alpha receptors and cytokines in
      the early phase of treatment for chronic hepatitis C: comparison between
      interferon (IFN)-alpha alone, IFN-alpha plus amantadine or plus ribavirin.
AB  - We have previously studied the effect of three different treatment regimens with
      interferon (IFN)-alpha alone or in combination with amantadine or ribavirin on
      viral kinetics in the first month of therapy. To understand the regulation of
      cytokine immune response during early inhibition of HCV replication, we analysed
      the longitudinal profile of proinflammatory markers (soluble TNFRs), of type 1
      cytokines [IFN-gamma and interleukin (IL-12)], and of a type 2 cytokine (IL-10).
      Twenty-two chronic hepatitis C patients received daily therapy for 6 months. Sera
      were collected at baseline, at 6, 12, 24, 30 and 48 h and at the 3rd, 7th, 15th
      and 30th days of treatment. All cytokines and receptors were evaluated by enzyme
      linked immunosorbent assay (ELISA). At baseline, a correlation was found between
      the two soluble TNFRs (P < 0.0001) and between the soluble TNFRs and ALT levels
      (P < 0.003), as shown previously. Regardless of the type of treatment, lower
      levels of soluble TNFR-p75 were present from day 3 in patients who had
      significant virus decay at day 30 (P < 0.01). Baseline IL-10 levels correlated
      with TNFR-p75 (P < 0.01) and with treatment response (P < 0.05) and a significant
      IL-10 reduction from baseline was observed from day 3 among responders,
      irrespective of the type of treatments (P < 0.05). IL-12 and IFN-gamma levels did
      not differ according to treatment or outcome. These findings suggest a pivotal
      role for IL-10 in orchestrating the antiviral immune response. Its early decline
      can favour the shift from a Th2 to a Th1 immune response, which has been shown to
      be associated with a long-term virological response to treatment.

PMID- 15147355
TI  - Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and
      TLR9 on the gastric epithelium in Helicobacter pylori infection.
AB  - Toll-like receptors (TLRs) expressed by mucosal epithelium play an essential role
      in the defense against microbes by recognizing conserved bacterial molecules. For
      the first time TLR4, TLR5 and TLR9 have been microanatomically localized in
      patients with noninflamed gastric mucosa and Helicobacter pylori gastritis by
      immunohistochemistry. Because polarized expression of TLRs in apical and
      basolateral epithelial compartments is thought to modulate mucosal immunity,
      subcellular TLR distribution by gastric epithelium was investigated using
      confocal microscopy. TLR4, TLR5 and TLR9 were expressed by gastric epithelium in
      antrum and corpus of all patients with H. pylori gastritis (n = 14) and with
      noninflamed gastric mucosa (n = 5). TLR4 was expressed at the apical and the
      basolateral pole of the gastric epithelium as well in noninflamed gastric mucosa
      as in H. pylori gastritis. TLR5 and TLR9 expression in the noninflamed gastric
      mucosa was identical to that of TLR4 with localization at the apical and the
      basolateral epithelial pole. However, in H. pylori gastritis TLR5 and TLR9
      expression on the gastric epithelium changed to an exclusive basolateral
      localization without detectable expression at the apical pole. In the human
      stomach, the gastric epithelium expressed TLR4, TLR5 and TLR9, which gives it the
      possibility to interact with H. pylori. Furthermore, gastric epithelial TLR4
      expression is highly polarized in an apical and a basolateral compartment,
      whereas TLR5 and TLR9 polarization seems to be a process dynamically influenced
      by H. pylori infection. This polarized and dynamically regulated gastric
      epithelial expression of TLRs supports a sentinel role for these receptors in the
      mucosal immunity to H. pylori.

PMID- 15147354
TI  - Influence of human T lymphotrophic virus type I on diffuse pan-bronchiolitis.
AB  - Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4(+)
      lymphocytes and is thought to modify their function and a possible association
      with pulmonary diseases has also been suggested. However, little is known about
      the influence of HTLV-I on diffuse pan-bronchiolitis (DPB), a chronic
      inflammatory lung disease with infiltration of lymphocytes and hyperplasia of the
      bronchus-associated lymphoid tissue. In this study, 35 DPB patients with and
      without HTLV-I infection were examined. HTLV-I positive DPB patients were likely
      to have a larger affected area with lower FEV(1). The CD3(+)/CD25(+) lymphocyte
      percentage was significantly higher in the BALF of HTLV-I positive patients than
      in negative patients. MIP-1 alpha, IP-10 and levels in BALF were also
      significantly higher in HTLV-I positive patients than in negative patients. The
      levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive
      patients, the MIP-1 alpha and IP-10 levels showed a significant positive
      correlation with the percentage of CD3(+)/CD25 lymphocytes. BALF cells of all
      HTLV-I positive DPB patients showed expression of p40(tax) mRNA. We suggest that
      HTLV-I infection may modify DPB pathogenesis via activation of T cells. We also
      found that the frequency of ATL development in HTLV-I positive DPB patients was
      significantly higher than in all HTLV-I positive patients (OR = 8.22, 95% CI =
      2.61-25.9, P < 0.01). The levels of TGF-beta in patients who developed ATL were
      significantly lower than in patients who did not develop ATL. Sensitivity and
      specificity were 80% and 85.7%, respectively (cut-off = 20 pg/ml). We also
      propose that these features should be taken into consideration in the treatment
      of DPB in HTLV-I infected individuals.

PMID- 15147357
TI  - Heterogeneity in cellular and humoral immune responses against Toxoplasma gondii
      antigen in humans.
AB  - Protection against Toxoplasma gondii in infected patients is mainly attributed to
      cellular immunity. We here attempt to improve the characterization of the
      proteins that induce cellular immunity in naturally infected patients. Cellular
      immunity was evaluated by flow cytometry after 7 days of blood culture from 31
      chronically T. gondii infected and 8 noninfected pregnant women, in the presence
      of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag,
      separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood
      cultures from infected patients with ST-Ag induced 39.5 +/- 12.7% of activated
      (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of
      activated CD4+ T cells after either culture with PBS or in blood cultures from
      noninfected women. The protein fraction between 21 and 41.9 kD induced the
      highest response (14.7 +/- 10.0%). Blood samples from 20 infected and 5
      uninfected women were cultured in presence of 12 protein subfractions of 2-208
      kD. The highest frequencies of response among infected patients were seen with
      fractions (Fr) 26-31.9 kD (C.I. 85-100%) and Fr 32-36.9 kD (C.I. 77-100%).
      Although we note a good concordance between cellular and humoral response,
      Western blot analysis of ST-Ag does not completely predict the panel of proteins
      recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed
      more than 200 protein spots in these fractions. However, only two proteins in the
      20-40 kD range induced a significant humoral response. Further studies are
      necessary to determine which proteins in the Fr 26-31.9 kD and 32-36.9 kD are
      superior immunogens for cellular responses.

PMID- 15147356
TI  - Structural and functional complexity of the humoral response against the
      Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas'
      heart disease.
AB  - High levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2
      beta ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have
      been measured in sera from patients with chronic Chagas' Heart Disease (cChHD).
      These antibodies also recognize an epitope on the second extracellular loop of
      the beta 1-adrenergic receptor, inducing a functional response on cardiomyocytes.
      The aim of this study was to gain novel insights into the structural basis of
      this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic
      receptor antibodies, which are also commonly found in cChHD patients. To address
      these questions we immunopurified anti-R13 antibodies and studied the structural
      requirements of epitope recognition. Results showed that the immunopurified
      antibodies recognized a conformation of R13 in which the third Glu residue was
      essential for binding, explaining their low affinity for the mammalian homologue
      (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual
      variations in epitope recognition in each of the studied patients. The importance
      of a negatively charged residue at position 3 for the recognition of anti-R13
      antibodies was further confirmed by competition experiments using a Ser3
      phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13
      antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated
      either the beta 1-adrenergic or the M2-cholinergic receptor, in strict agreement
      with the functional properties of the IgG fractions from which they derived,
      demonstrating that the same parasite antigen may generate antibody specificities
      with different functional properties. This may be a clue to explain the high
      variability of electrophysiological disturbances found in cChHD.

PMID- 15147358
TI  - Increase in granzyme B+ lymphocytes and soluble granzyme B in bronchoalveolar
      lavage of allergen challenged patients with atopic asthma.
AB  - Asthma has been linked to a chronic, T-cell-mediated bronchial inflammation.
      Because other T-lymphocyte-mediated, chronic inflammatory disorders have been
      associated with elevated granzyme B (grB) expression we tested the hypothesis
      that atopic asthma might be associated with elevated grB levels in the
      bronchoalveolar compartment. Therefore we performed intracellular grB staining in
      lymphocytes from bronchoalveolar lavage (BAL) collected 42 h after segmental
      allergen provocation (SAP) in allergic patients with bronchial asthma. There was
      a significant increase in CD3(+), CD8(+), and CD16/56(+) lymphocytes expressing
      grB in BAL 42 h after SAP as compared to saline challenged controls. However,
      compared to peripheral blood the percentages of these lymphocyte subsets detected
      as grB(+) in BAL remained significantly lower. Measurement of extracellular grB
      in BAL fluids by a particle immunoassay revealed significantly elevated grB
      levels in the allergen challenged bronchoalveolar compartment 42 h following SAP
      in six of the eight patients (range, <1.0-348.1 pg/ml) as compared to saline
      challenged controls (range, <1.0-70.5 pg/ml). We conclude that total cell numbers
      of grB(+) lymphocyte subsets increase 42 h after SAP in the lower respiratory
      tract. In addition there is evidence to suggest that grB is released into the
      airways of asthmatic patients. This suggests a role for grB in the
      pathophysiological processes following SAP but its definitive role in allergic
      bronchial asthma needs to be established.

PMID- 15147359
TI  - Redox status and immune function in type I diabetes families.
AB  - Because abnormalities in redox balance cluster in type I diabetes families and
      the intracellular thiol redox status seems to modulate immune function, we aimed
      to investigate the relationship between oxidative stress and immunological
      features. We measured oxidative markers, serum proinflammatory cytokines, soluble
      cytokine receptors and subsets of peripheral blood lymphocytes (by varying
      combinations of CD4, CD8, CD23 or low-affinity IgE receptor, and CD25 or IL-2
      receptor) from 38 type I patients, 76 low-risk (i.e. without underlying islet
      autoimmunity) non-diabetic first-degree relatives of diabetic patients, and 95
      healthy subjects. In type I diabetes families, protein and lipid oxidation was
      confirmed by the presence of reduced sulphhydryl groups, increased advanced
      oxidation protein products, and increased plasma and erythrocyte malondialdehyde.
      Relatives had decreased counts of monocytes, of cells co-expressing CD23 and CD25
      and of CD25(+) cells in peripheral blood. Patients with TIDM had similar defects
      and, in addition, showed decreased counts of peripheral CD4(+)CD8(+) lymphocytes
      and increased serum levels of soluble receptors for interleukin (IL)-6 and IL-2.
      Abnormal indicators of oxidative stress were related in part to immune
      abnormalities. In the whole study group, we found a correlation (multiple R 0.5,
      P < 0.001) of CD23(+)CD25(+) cells with blood counts of monocytes, CD4(+)CD8(+)
      cells, CD25(+) cells, basal haemolysis and plasma levels of thiols. In type I
      diabetics, anti-GAD65 antibody levels were associated (multiple R 0.6, P = 0.01)
      positively with sIL-6R, negatively with duration of diabetes and CD23(+)CD25(+)
      counts; plasma creatinine correlated positively (multiple R 0.6, P < 0.001) with
      both sIL-2R and tumour necrosis factor (TNF)-alpha concentration. Our study
      reports the first evidence that the oxidative stress observed in type I families
      is related to immunological hallmarks (decreased peripheral numbers of monocytes
      as well as cells bearing a CD4(+)CD8(+), CD23(+)CD25(+) and CD25(+) phenotype)
      from which the involvement of some immunoregulatory mechanisms could be
      suspected. It remains to be elucidated the course of events culminating in the
      loss of physiological immune homeostasis and disease pathology.

PMID- 15147360
TI  - Decrease of CD154 intensity on peripheral CD4+ T cells in autoimmune thyroid
      disease.
AB  - To clarify immunological differences among patients with Graves' disease (GD) and
      Hashimoto's disease (HD) at various levels of severity, we examined the
      expression of the CD154 molecules on peripheral T cells, which regulate B cell
      activation, B cell differentiation, and T-cell survival. We found decreases in
      the intensities of CD154 on peripheral CD4(+) cells from euthyroid patients with
      GD and HD, but we did not find any differences between patients with different
      disease severities. CD8(+) cells did not express CD154 molecules. Thus, CD154
      expression on CD4(+) cells may be related to the pathogenesis of the autoimmune
      thyroid diseases, not to the disease severity.

PMID- 15147361
TI  - Apoptosis as a mechanism for cell surface expression of the autoantigen pyruvate
      dehydrogenase complex.
AB  - A number of antigens implicated in the pathogenesis of autoimmune diseases
      including Sjogren's syndrome and systemic lupus erythematosus (SLE) are expressed
      aberrantly by apoptotic cells. It is also known that apoptogenic proteins are
      released from the mitochondrial intermembrane space at an early stage during the
      induction and development of apoptosis. Combination of this evidence led us to
      test the hypothesis that apoptotic mechanisms provide an explanation for the
      abnormal expression of the inner mitochondrial enzyme, pyruvate dehydrogenase
      complex (PDC), observed on the surface of some cells in patients with the
      autoimmune liver disease primary biliary cirrhosis (PBC). Using one murine and
      two human cell lines it was found that the induction of apoptosis led to early
      detection of PDC within the cytoplasm. However, cytochrome c oxidase subunit 4
      (COX 4), which is also present on the inner surface of the inner mitochondrial
      membrane, remained within the mitochondria. Immunoreactive PDC was also detected
      on the outer surface of the intact plasma membrane of cells sampled after the
      induction of apoptosis. Serial release of PDC to the cytoplasm and then onto the
      external surface of the plasma membrane provides direct evidence that the antigen
      on the cell surface is of mitochondrial origin. Immunoreactivity specific for PDC
      is strongly implicated in the pathogenesis of PBC, but this autoantigen is
      normally concealed from the immune system by three membrane systems. Release of
      PDC onto the cell surface during apoptosis provides a possible route for
      recognition of this antigen by the immune system which could contribute to both
      afferent and efferent phases of the disease process.

PMID- 15147362
TI  - Autoantibodies from primary biliary cirrhosis patients with anti-p95c antibodies
      bind to recombinant p97/VCP and inhibit in vitro nuclear envelope assembly.
AB  - We have reported previously that p95c, a novel 95-kDa cytosolic protein, was the
      target of autoantibodies in sera of patients with autoimmune hepatic diseases. We
      studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein
      from [(35)S]-methionine-labelled HeLa lysates and had a specific precipitin band
      in immunodiffusion. Thirteen sera were available to test the ability of p95c
      antibodies to inhibit nuclear envelope assembly in an in vitro assay in which
      confocal fluorescence microscopy was also used to identify the stages at which
      nuclear assembly was inhibited. The percentage inhibition of nuclear envelope
      assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and
      the swelling of nucleus was inhibited at several stages. The percentage
      inhibition of nuclear assembly was correlated with the titre of anti-p95c as
      determined by immunodiffusion. To confirm the identity of this autoantigen, we
      used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a
      radiolabelled recombinant protein that was then used in an immunoprecipitation
      (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with
      antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97
      have similar molecular masses and cell localization, and because the majority of
      sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly,
      this is compelling evidence that p95c and p97/VCP are identical.

PMID- 15147363
TI  - Over-expression of TATA binding protein (TBP) and p53 and autoantibodies to these
      antigens are features of systemic sclerosis, systemic lupus erythematosus and
      overlap syndromes.
AB  - The aim of this study was to determine the expression levels of p53 and TATA
      binding protein (TBP) and the presence of autoantibodies to these antigens in
      Asian Indian patients with systemic sclerosis (SSc), overlap syndromes (OS) and
      systemic lupus erythematosus (SLE). Fifty patients with SSc, 20 with OS,
      including mixed connective tissue diseases (MCTD), 20 with SLE, 10 disease
      controls (DC) and 25 controls (C) were studied. The over-expression of p53 and
      TBP antigen was determined quantitatively by sandwich enzyme-linked immunosorbent
      assay (ELISA), varies between four- and sevenfold higher in patients with SSc, OS
      and SLE, in comparison to DC and C. The expressed protein antigens were not
      present as free antigens but as immune-complexes. Autoantibodies to p53 were
      detected by ELISA in 78% subjects with SSc, 100% with OS and 80% with SLE.
      Autoantibodies to TBP were observed in 28% patients with SSc, 25% with OS and 15%
      with SLE. In comparison to healthy controls, the titre of antibodies to p53 was
      significantly higher in patients with SSc (P = 0.00001) than the patients with OS
      (P = 0.00279) and SLE (P = 0.00289), whereas the titre of antibodies to TBP was
      higher in patients with OS (P = 0.00185) than the SLE (P = 0.00673) and the SSc
      (P = 0.00986) patients. Autoantibodies to p53 and TBP were detected in all these
      patients and the levels of these two autoantibodies showed weak negative
      correlation with each other. We propose that the over-expression of these
      antigens might be due to hyperactive regulatory regions in the p53 and TBP gene.

PMID- 15147364
TI  - Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic
      lupus erythematosus.
AB  - Mannose-binding lectin (MBL) is a key element in innate immunity with functions
      and structure similar to that of complement C1q. It has been reported that MBL
      deficiency is associated with occurrence of systemic lupus erythematosus (SLE).
      We hypothesized that anti-MBL antibodies, if present, would affect the occurrence
      or disease course of SLE, by reduction of serum MBL levels, interference of MBL
      functions, or binding to MBL deposited on various tissues. To address this
      hypothesis, we measured the concentration of anti-MBL antibodies in sera of 111
      Japanese SLE patients and 113 healthy volunteers by enzyme immunoassay. The
      titres of anti-MBL antibodies in SLE patients were significantly higher than
      those in healthy controls. When the mean + 2 standard deviations of controls was
      set as the cut off point, individuals with titres of anti-MBL antibodies above
      this level were significantly more frequent in SLE patients (9 patients) than in
      controls (2 persons). One SLE patient had an extremely high titre of this
      antibody. No associations of titres of anti-MBL antibodies and (i) genotypes of
      MBL gene, (ii) concentrations of serum MBL, or (iii) disease characteristics of
      SLE, were apparent. Thus, we have confirmed that anti-MBL antibodies are indeed
      present in sera of some patients with SLE, but the significance of these
      autoantibodies in the pathogenesis of SLE remains unclear.

PMID- 15147366
TI  - Schizophrenia and refractory anaemia with ring sideroblasts.

PMID- 15147365
TI  - Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of
      Wegener's granulomatosis and relapsing polychondritis.
AB  - The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V
      beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer
      loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in
      peripheral blood mononuclear cells (PBMCs) of patients with Wegener's
      granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN
      and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer
      tetramer-positive NKT cells, were significantly decreased in number in both WG
      and RP patients compared to those from HS. When cytokine profiles were analysed
      in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+)
      T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT
      cells from WG patients in remission showed a Th2 bias. These findings suggest
      that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1
      autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears
      to be associated with the low responsiveness to alpha-GalCer. The dysfunction of
      NKT cells to recognize ligands such as alpha-GalCer may also contribute to the
      defects observed in NKT cells from WG and RP patients.

PMID- 15147367
TI  - Multiple lymphomatous polyposis.

PMID- 15147368
TI  - Purging iron from the heart.
AB  - Methods are now available to measure the magnitude of iron accumulation in the
      heart. Their validation currently relies on indirect evidence and not on chemical
      estimation in cardiac biopsies. All patients with symptomatic heart disease
      appear to have abnormal T2* values, but many patients without symptomatic heart
      disease also have evidence of increased myocardial iron. Although there is no
      proof to date that increased myocardial iron, as evidenced by abnormal magnetic
      resonance imaging, carries an adverse prognosis, it is likely that such new
      information will affect the chelating programme of patients. In these cases,
      there are a number of options available: (i) ongoing treatment with either
      desferrioxamine (DFO) or deferiprone may be intensified; (ii) the patient may be
      switched to the alternative chelator or (iii) combined chelation with both DFO
      and deferiprone may be started, which is more effective than using either
      chelator alone. For patients with symptomatic heart disease, continuous
      intravenous DFO with, or without deferiprone, remains the currently recommended
      treatment, in view of its documented ability to salvage these patients.

PMID- 15147369
TI  - Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia.
AB  - This study of children and adults with acute lymphoblastic leukaemia (ALL) is the
      largest series of patients with hypodiploidy (<46 chromosomes) yet reported. The
      incidence of 5% was independent of age. Patients were subdivided by the number of
      chromosomes; near-haploidy (23-29 chromosomes), low hypodiploidy (33-39
      chromosomes) and high hypodiploidy (42-45 chromosomes). The near-haploid and low
      hypodiploid groups were characterized by their chromosomal gains and a doubled
      hyperdiploid population. Structural abnormalities were more frequent in the low
      hypodiploid group. Near-haploidy was restricted to children of median age 7 years
      (range 2-15) whereas low hypodiploidy occurred in an older group of median age 15
      years (range 9-54). Patients with 42-45 chromosomes were characterized by complex
      karyotypes involving chromosomes 7, 9 and 12. The features shared by the few
      patients with 42-44 chromosomes and the large number with 45 justified their
      inclusion in the same group. Survival analysis showed a poor outcome for the near
      haploid and low hypodiploid groups compared to those with 42-45 chromosomes. Thus
      cytogenetics, or at least a clear definition of the modal chromosome number, is
      essential at diagnosis in order to stratify patients with hypodiploidy into the
      appropriate risk group for treatment.

PMID- 15147370
TI  - E4BP4 expression is regulated by the t(17;19)-associated oncoprotein E2A-HLF in
      pro-B cells.
AB  - The E4BP4 basic leucine zipper (bZIP) transcription factor is regulated by
      interleukin-3 (IL-3) in pro-B cells and has been reported to promote survival of
      the murine IL-3-dependent pro-B cell lines, FL5.12 and Baf-3. The E2A-HLF
      oncoprotein arises from a t(17;19) translocation in childhood pro-B cell acute
      lymphoblastic leukaemia and acts as an anti-apoptotic factor in FL5.12 and Baf-3
      cells. To assess the functions of E2A-HLF and E4BP4 in cell survival, a
      tetracycline-inducible system was established in Baf-3 cells to express E4BP4 or
      E2A-HLF. Upon IL-3 withdrawal, expression of E2A-HLF conferred resistance to
      apoptosis whereas overexpression of E4BP4 did not. E4BP4 and E2A-HLF both
      recognized the same DNA sequence in reporter gene assays, but had opposite
      effects on transcription. E2A-HLF acts as a transcriptional activator and E4BP4
      as a transcriptional repressor. Furthermore, E4BP4 is a downstream
      transcriptional target of E2A-HLF. Our data suggests that the overexpression of
      E4BP4 is unable to block apoptosis induced by IL-3 withdrawal and that the
      expression of E2A-HLF does not replace the function of E4BP4 in mediating
      survival.

PMID- 15147371
TI  - Depletion and impaired interferon-alpha-producing capacity of blood plasmacytoid
      dendritic cells in human T-cell leukaemia virus type I-infected individuals.
AB  - Dendritic cells (DCs) play an important role in innate and adaptive immunity.
      There are two major populations of blood DCs, myeloid DCs (myDCs) and
      plasmacytoid DCs (pcDCs). pcDCs are particularly important in antiviral as well
      as in general host defence, as they are the principal producers of type I
      interferons (IFNs). In this study, we analysed myDCs and pcDCs in healthy
      controls, human T-cell leukaemia virus type I (HTLV-I)-infected asymptomatic
      carriers (ACs), and patients with adult T-cell leukaemia (ATL). ATL patients had
      significantly decreased number of pcDCs and myDCs compared with controls. IFN
      alpha production by peripheral blood mononuclear cells (PBMCs) was markedly
      reduced in ATL patients. Purified pcDCs from ACs were found to have impaired IFN
      alpha-producing capacity, suggesting a functional defect in pcDCs in HTLV-I
      infected individuals. Interestingly, pcDCs were shown to be susceptible to HTLV-I
      infection. Thus, impaired IFN-alpha production by pcDCs may contribute to the
      immunodeficiency observed in ATL. Furthermore, IFN-alpha-producing capacity was
      inversely correlated with HTLV-I proviral load in PBMCs from ACs, suggesting a
      role for pcDCs in maintaining the carrier state. Taken together, we hypothesize
      that the depletion and impaired IFN-alpha-producing capacity of blood DCs may
      contribute to the immunodeficiency in ATL and/or the development of ATL.

PMID- 15147372
TI  - Gene expression profiling in the myelodysplastic syndromes using cDNA microarray
      technology.
AB  - The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal
      disorders of the haematopoietic stem cell and primarily involve cells of the
      myeloid lineage. Using cDNA microarrays comprising 6000 human genes, we studied
      the gene expression profiles in the neutrophils of 21 MDS patients, seven of
      which had the 5q- syndrome, and two acute myeloid leukaemia (AML) patients when
      compared with the neutrophils from pooled healthy controls. Data analysis showed
      a high level of heterogeneity of gene expression between MDS patients, most
      probably reflecting the underlying karyotypic and genetic heterogeneity.
      Nevertheless, several genes were commonly up or down-regulated in MDS. The most
      up-regulated genes included RAB20, ARG1, ZNF183 and ACPL. The RAB20 gene is a
      member of the Ras gene superfamily and ARG1 promotes cellular proliferation. The
      most down-regulated genes include COX2, CD18, FOS and IL7R. COX2 is anti
      apoptotic and promotes cell survival. Many genes were identified that are
      differentially expressed in the different MDS subtypes and AML. A subset of genes
      was able to discriminate patients with the 5q- syndrome from patients with
      refractory anaemia and a normal karyotype. The microarray expression results for
      several genes were confirmed by real-time quantitative polymerase chain reaction.
      The MDS-specific expression changes identified are likely to be biologically
      important in the pathophysiology of this disorder.

PMID- 15147373
TI  - ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced
      Hodgkin's lymphoma: a retrospective analysis.
AB  - We retrospectively analysed toxicities and clinical results of 61 Hodgkin's
      lymphoma patients treated with chlorambucil, vinblastine, procarbazine,
      doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a
      weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage
      IIB and seven in stage IIA with bulky disease or extranodal presentation.
      ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT)
      (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy
      or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete
      clinical or radiological remission after chemotherapy and IFRT. With a median
      follow-up of 60 months, 5-year overall survival, relapse- and event-free survival
      were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2
      82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological
      toxicity and occurred in 82% of patients. Non-haematological toxicities were mild
      and reversible. No toxic deaths were recorded. One patient developed secondary
      acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective
      nature of this study, no definitive conclusions could be drawn about the clinical
      activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those
      reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine,
      dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone),
      MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP
      (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine
      and prednisone), with a lower degree of haematological and non-haematological
      toxicity. Long-term results of the ongoing randomized trial, comparing ABVD
      versus high-dose intensity weekly regimens will be useful to confirm our results.

PMID- 15147374
TI  - WT1 gene expression: an excellent tool for monitoring minimal residual disease in
      70% of acute myeloid leukaemia patients - results from a single-centre study.
AB  - Following induction chemotherapy for acute myeloid leukaemia (AML), sensitive
      determination of minimal residual disease (MRD) in patients achieving complete
      remission (CR) should enable the detection of early relapse and allow
      intervention at a more favourable stage than at overt relapse. We have determined
      the expression levels of the Wilms' tumour gene (WT1) by real-time quantitative
      polymerase chain reaction (RQ-PCR) in peripheral blood and bone marrow in 133
      newly diagnosed AML patients and compared them with those in healthy volunteers.
      At diagnosis, the WT1 level exceeded normal expression in 118 of 133 (89%)
      patients, and was high enough to allow for detection of a WT1 decrease of least
      1000-fold in 98 of 133 (74%) patients following induction therapy. Concomitant
      monitoring of fusion transcripts (PML-RARalpha, AML1-ETO, MLL-MLL, CBFbeta-MYH11,
      or DEK-CAN) in 38 patients identified different relationships between WT1 and
      fusion transcript levels, the AML1-ETO group showing remarkably low levels of WT1
      compared with fusion transcript. In 32 patients analysed longitudinally there was
      close concordance between relapse and increased WT1 levels. Parallel longitudinal
      monitoring of WT1 and fusion transcript showed close correlation in 18 of 18
      patients. We conclude that WT1 expression by RQ-PCR may be employed as a tool to
      detect MRD in the majority of fusion transcript-negative AML patients.

PMID- 15147375
TI  - Variant MYST4-CBP gene fusion in a t(10;16) acute myeloid leukaemia.
AB  - We report a novel fusion of the MYST4 and CBP genes in an acute myeloid leukaemia
      (AML)-M4 patient exhibiting t(10;16)(q22;p13) and t(11;17)(q23;q21). The
      t(10;16)(q22;p13) resulted in a rearrangement, where MYST4-CBP and CBP-MYST4
      chimaeric transcripts were products of in-frame fusions of MYST4 exon 17 to CBP
      exon 6 and CBP exon 4 to MYST4 exon 18 respectively. The potential resulting
      chimaeric proteins showed similarities with MYST3-CBP, MYST3-P300 and MYST3-NCOA2
      putative fusion proteins found in other cases of AML.

PMID- 15147376
TI  - Infused CD34 cell dose, but not tumour cell content of peripheral blood
      progenitor cell grafts, predicts clinical outcome in patients with diffuse large
      B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose therapy.
AB  - Previously, we have shown that patients with diffuse large B-cell lymphoma
      (DLBCL) transplanted with contaminated bone marrow (BM) generally have a poor
      outcome. Whether this is also the case when peripheral blood progenitor cell
      (PBPC) grafts are used is not known. Forty-three patients with chemosensitive
      DLBCL or follicular lymphoma grade 3 (FLgr3) were treated with high-dose therapy
      (HDT) and autologous stem cell support. Nine patients received purged grafts.
      Quantitative real-time polymerase chain reaction (QRT-PCR) for either the
      BCL2/IgH translocation or allele specific oligonucleotide (ASO) QRT-PCR for the
      immunoglobulin heavy chain (IgH) complementarity-determining region 3 were used.
      Nine of 25 (36%) PBPC grafts contained tumour cells as tested by QRT-PCR,
      including two grafts purged by CD34(+) cell enrichment combined with B-cell
      depletion. The level of contamination of the PBPC/CD34(+) cells ranged from 0 to
      8.28%. No relationship could be shown between the total number of tumour cells
      infused and relapse. Patients receiving PCR-positive or PCR-negative PBPC grafts
      had similar progression-free survival (PFS) (P = 0.49). However, a significant
      difference was seen in PFS and overall survival (OS) for the patients given
      >/=6.1 x 10(6) CD34(+) cells/kg compared with those given <6.1 x 10(6) CD34(+)
      cells/kg (P = 0.01 and P < 0.05 respectively).

PMID- 15147377
TI  - Validation and extension of the EBMT Risk Score for patients with chronic myeloid
      leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants.
AB  - The European Group for Blood and Marrow Transplantation (EBMT) devised a scoring
      system to predict survival after allogeneic haematopoietic stem cell
      transplantation (HSCT) for chronic myeloid leukaemia (CML). The present
      International Bone Marrow Transplant Registry study of 3211 patients tested the
      EBMT Risk Score in a independent population, investigated the value of adding
      other variables, evaluated a new risk score specifically for chronic phase and
      compared the allograft risk scores with risk scores established by Sokal in 1984
      and Hasford in 1998 for survival with non-transplant treatments. The primary
      outcome was 5-year survival after HSCT; survival curves, regression models and
      measurements of explained variation were used to compare scores. Using the EBMT
      scoring system, survival in the independent dataset was almost identical to those
      in the original EBMT publication, thus validating the EBMT Risk Score. Adding one
      extra variable, performance status, or designing a score specifically for early
      chronic phase by using the original five variables with different breakpoints
      gave results only slightly better than the original EBMT Score. Sokal and Hasford
      Scores did not predict survival after HSCT. We concluded that the EBMT Risk Score
      does not currently require modification.

PMID- 15147378
TI  - Genetic variants of the extra-large stimulatory Gs protein alpha-subunit and risk
      of thrombotic and haemorrhagic disorders.
AB  - A polymorphism of the gene encoding the extra-large stimulatory G-protein alpha
      subunit (XLalphas), originally identified in three patients with a bleeding
      tendency, involved a 36-bp insertion and two missense changes. A paternally
      inherited insertion displayed a moderate platelet Gsalpha over-expression, which
      lead to platelet hypo-reactivity. These data prompted us to investigate the
      genetic, functional and clinical relevance of this polymorphism in the
      Mediterranean population. We included 414 healthy subjects and three case/control
      studies: 263 consecutive patients with a first episode of primary intracerebral
      haemorrhage, 195 patients with deep venous thrombosis, and 104 patients with
      cerebrovascular disease. Controls were selected by approximating criteria to
      match selected risk factors to patients. Moreover, we performed studies of
      platelet function. We developed a simple method to determine the methylated
      allele, by digestion of genomic DNA with Sma I before polymerase chain reaction
      amplification. We identified two new rare variants, resulting from the loss of
      repeat units 7 and 5. The AB genotype was present in 3.6% of healthy population
      and the prevalence of the B allele was similar among cases and controls.
      Accordingly, the non-methylated B allele did not modify either the expression of
      platelet Gsalpha or the platelet response to Gs-agonists. Thus, our study
      suggests a minor functional role of XLalphas polymorphism in thrombotic or in
      haemorrhagic disorders.

PMID- 15147379
TI  - Mutation of the surface-exposed amino acid Trp to Ala in the FVIII C2 domain
      results in defective secretion of the otherwise functional protein.
AB  - The C2 domain of factor VIII (FVIII) is important for FVIII-phospholipid (PL) and
      FVIII-von Willebrand factor (VWF) interactions. A FVIII structural model, derived
      by electron crystallography, suggests four hydrophobic loops at the FVIII C2
      domain-PL interface. Within loop four, the solvent-exposed amino acid, Trp(2313),
      is believed to contribute to FVIII-PL binding. To analyse this interaction, the
      amino-acid exchange Trp(2313) to Ala (W2313A) was introduced into the C2 domain
      of B-domain-deleted FVIII (dBFVIII). Both proteins, dBFVIII and W2313A, were
      expressed in a mammalian expression system. Labelling experiments showed that the
      mutation W2313A resulted in reduced secretion but did not affect intracellular
      synthesis of the protein. Specific activity, kinetic parameters, binding to VWF
      and haemostatic potential in a murine model of haemophilia A were found to be
      similar for both proteins. Binding studies to synthetic 4% phosphatidyl-l-serine
      vesicles showed, however, a 28-fold higher K(D) for W2313A, indicating the
      important role of Trp(2313) in the FVIII-PL interaction. In conclusion, the C2
      domain-surface-exposed residue Trp(2313), is critical for secretion of the
      protein. The W2313A mutation weakens binding to phosphatidyl-l-serine vesicles
      but the mutant protein has the same effector function as dBFVIII in vitro and in
      vivo.

PMID- 15147381
TI  - The prevalence of, and molecular defects underlying, inherited protein S
      deficiency in the general population.
AB  - The molecular basis of protein S (PS) deficiency was investigated in seven of
      eight donors identified with persistently low plasma PS levels from a survey of
      PS levels in 3788 Scottish blood donors. PROS1 gene analysis identified at least
      one defect in six donors. Five were heterozygous for the Heerlen polymorphism
      predicting a Ser460Pro substitution. Haplotype analysis revealed the possibility
      that this allele was inherited with the same haplotype in four of the five
      donors, suggesting a founder effect for the Heerlen allele in this population.
      One Heerlen allele carrier was also heterozygous for a 3 bp deletion 68-72 bp
      upstream of exon 2. Platelet PROS1 transcript analysis showed no reduction in
      mRNA expression from the affected allele in this donor. A T to G transversion 3
      bp upstream of exon 12 was identified in one donor, which is predicted to reduce
      the efficiency of PS mRNA splicing. However, PROS1 transcript analysis showed no
      evidence of exon skipping or cryptic splicing. No PROS1 gene defect was detected
      in the remaining donor. This genetic information enabled us to refine our
      estimate of the prevalence of heritable PS deficiency in the Scottish population
      to between 0.16% and 0.21%, predominantly resulting from the presence of the
      Heerlen allele.

PMID- 15147380
TI  - Secretion of functional plasma haemostasis proteins in long-term primary cultures
      of human hepatocytes.
AB  - This study was designed to investigate the ability of long-term primary cultures
      of adult human hepatocytes to secrete the main haemostasis proteins. Factors II,
      V, VII, VIII, PIVKA-II (protein induced by vitamin K 1 absence or antagonist II),
      fibrinogen and antithrombin were quantified in culture medium by immunological
      methods and by measuring the coagulant activity of factors II, V and VII. All the
      haemostasis protein antigens except the factor VIII antigen (FVIII:Ag) were found
      in the culture medium throughout the culture period. The clotting activity of
      each factor correlated well with antigen level. In addition, fibrinogen and
      fibrin were detected in the fibrillar material following incubation of the
      culture medium with thromboplastin. Moreover, adding vitamin K 1 to the culture
      medium resulted in a significant increase of factors II and VII and a reciprocal
      decrease of the PIVKA-II, and adding von Willebrand factor resulted in a drastic
      increase of the level of FVIII:Ag. We conclude that, in our culture system,
      normal adult human hepatocytes retain their capacity to secrete haemostasis
      proteins for at least 30 days.

PMID- 15147382
TI  - Characterisation of Mcl-1 cleavage during apoptosis of haematopoietic cells.
AB  - Mcl-1 is essential for normal haematopoiesis, being required for lymphocyte
      development and maintenance. Its role in haematopoietic differentiation and
      development is associated with its function as an anti-apoptotic member of the
      Bcl-2 family of proteins although the underlining mechanism is poorly understood.
      We have characterized caspase cleavage of the Mcl-1 protein during apoptosis.
      Caspase cleavage resulted in the removal of the PEST regions from the protein and
      generation of a fragment containing the BH-1, -2 and -3 homology domains. Removal
      of the PEST regions did not appear to alter Mcl-1 stability, suggesting that
      these regions are not responsible for Mcl-1's short half-life. In addition,
      unlike cleavage of Bcl-2 and Bcl-X(L), which resulted in pro-apoptotic fragments,
      cleaved forms of Mcl-1 were unable to induce apoptosis. This novel regulation of
      Mcl-1 may have important implications not only for its role in apoptosis but also
      for the essential role it plays in the differentiation and development of
      haematopoietic cells.

PMID- 15147385
TI  - Abstracts of the British Association of Urological Surgeons Annual Meeting,
      Harrogate, United Kingdom, 21-25 June, 2004.

PMID- 15147384
TI  - Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense
      mutation (R105X) in two siblings of north French descent.
AB  - The molecular basis of hereditary hemochromatosis (HH) is more complex than
      previously expected. More than 80% of hemochromatosis probands of Northern
      European descent are homozygous for the C282Y HFE gene mutation. However, five
      novel non-related-HFE HH forms have now been identified. The transferrin
      receptor(TFR2)-linked form is inherited in an autosomal recessive pattern and is
      considered to be an adult-onset syndrome. Until now, it has been associated with
      five mutations that have only been detected in Japanese and southern European
      patients. Here, we report the identification of a novel TFR2 nonsense mutation in
      two related French adolescents. We discuss the phenotype of this sibling pair
      from precedent biological and clinical findings as well as the expected role of
      TFR2 in iron homeostasis. Finally, we suggest that iron overload phenotypes
      associated with mutations in TFR2 may be intermediate between those related to
      mutations in HFE and those related to mutations in juvenile hemochromatosis
      genes.

PMID- 15147383
TI  - Subcellular localization and mobilization of carcinoembryonic antigen-related
      cell adhesion molecule 8 in human neutrophils.
AB  - The subcellular localization and mobilization of carcinoembryonic antigen-related
      cell adhesion molecule 8 (CEACAM8) was investigated quantitatively in human
      neutrophils. In resting neutrophils the majority of CEACAM8 was present in the
      secondary granules, and a small amount of CEACAM8 was present in a light membrane
      fraction. Stimulation of the neutrophils with phorbol 12-myristate 13-acetate
      caused a dramatic increase in the content of CEACAM8 in the light membrane
      fraction, suggesting a translocation of CEACAM8 to the plasma membrane from
      intracellular pools. The cellular content of CEACAM8 in the neutrophils was
      estimated to be 82.4 +/- 8.9 ng/10(6) cells (mean +/- SE, n = 10). Administration
      of granulocyte colony-stimulating factor (G-CSF) to healthy individuals resulted
      in an increased content of CEACAM8 in neutrophils on day 1, which decreased on
      day 4. However, the content of CEACAM8 in the light membrane fraction was
      increased on day 4, possibly due to the stimulation by induced secondary
      cytokines, such as tumour necrosis factor-alpha (TNF-alpha). This study
      establishes the secondary granules as the major intracellular pools of CEACAM8 in
      human neutrophils, from which it may translocate to the plasma membranes upon
      stimulation of the cells. The translocation of CEACAM8 seen in vivo after G-CSF
      administration is probably indirect and caused by cytokines such as TNF-alpha.

PMID- 15147386
TI  - The chicken proinflammatory cytokines interleukin-1beta and interleukin-6:
      differences in gene structure and genetic location compared with their mammalian
      orthologues.
AB  - The genes encoding the chicken proinflammatory cytokines interleukin (IL)-1B and
      IL-6 were cloned, sequenced and mapped. The exon:intron structure of the coding
      region of chicken IL1B corresponds almost exactly to those of mammalian IL1B. As
      yet, we have no evidence for a 5'-UTR non-coding exon equivalent to that found in
      mammalian IL1B. The exon:intron structure of chicken IL6 differs from those of
      mammalian IL6, having one exon fewer (the first two exons in mammalian IL6 genes
      appear to be fused in the chicken gene). We were unable to clone or sequence the
      promoter of chicken IL1B. The chicken IL6 promoter shares a number of potential
      regulatory sequences similar to those found in the human IL6 promoter. These
      putative elements include (5'-3') a glucocorticoid response element (GRE), an AP
      1 binding site, an NF-IL-6 binding site (albeit in the reverse orientation), an
      NF-kappaB binding site, a second AP-1 binding site and a TATAAA box. A further
      GRE, a cAMP response element and regions with homology to c-fos serum responsive
      elements or retinoblastoma control elements were absent. Promoter sequence
      polymorphisms were not identified in eight different inbred chicken lines. A
      restriction single-stranded conformational polymorphism was identified which
      enabled chicken IL1B to be genetically mapped to one end of chromosome 2. Chicken
      IL6 was mapped by fluorescent in situ hybridization also to chromosome 2, at an
      FLpter of 0.26.

PMID- 15147387
TI  - Close linkage of genes encoding receptors for subgroups A and C of avian
      sarcoma/leucosis virus on chicken chromosome 28.
AB  - Avian sarcoma and leucosis viruses (ASLV) are classified into six major subgroups
      (A to E and J) according to the properties of the viral envelope proteins and the
      usage of cellular receptors for virus entry. Subgroup A and B receptors are
      identified molecularly and their genomic positions TVA and TVB are mapped. The
      subgroup C receptor is unknown, its genomic locus TVC is reported to be
      genetically linked to TVA, which resides on chicken chromosome 28. In this study,
      we used two chicken inbred lines that carry different alleles coding for
      resistance (TVC(R) and sensitivity (TVC(S)) to infection by subgroup C viruses. A
      backross population of these lines was tested for susceptibility to subgroup C
      infection and genotyped for markers from chicken chromosome 28. We confirmed the
      close linkage between TVA and TVC loci. Further, we have described the position
      of TVC on chromosome 28 relative to markers from the consensus map of the chicken
      genome.

PMID- 15147388
TI  - Genetic polymorphisms and antiviral activity in the bovine MX1 gene.
AB  - Bovine MX1 cDNAs consisting of 2280 bp from 11 animals of five breeds and from a
      cultured cell line were sequenced and compared with previously reported data. Ten
      nucleotide substitutions were synonymous mutations, and a single nucleotide
      substitution at 458 resulted in an amino acid exchange of Ile (ATT) and Met
      (ATG). A 13-bp deletion-insertion mutation was also found in the 3'-UTR. Based on
      the nucleotide substitutions found in this study, bovine MX1 cDNA was classified
      into 11 genotypes. A phylogenetic tree of the 11 genotypes suggested that the
      genotypes observed in Brahman were a great genetic distance from other genotypes.
      An 18-bp deletion-insertion variation at position 171 was found to be the result
      of alternative splicing. The 18-bp deletion-insertion is located at the boundary
      between exon 3 and intron 3. Permanently transfected 3T3 cell lines expressing
      bovine MX1 mRNA were established to analyse the antiviral potential against
      VSVDeltaG*-G infection. Transfected cell clones expressing bovine MX1 mRNA showed
      a significantly smaller number of cells infected with VSVDeltaG*-G compared with
      the control cells. These results indicate that the bovine MX1 protein has potent
      antiviral activity.

PMID- 15147389
TI  - Genetic mapping of quantitative trait loci affecting body weight, egg character
      and egg production in F2 intercross chickens.
AB  - Phenotypic measurements of chicken egg character and production traits are
      restricted to mature females only. Marker assisted selection of immature chickens
      using quantitative trait loci (QTL) has the potential to accelerate the genetic
      improvement of these traits in the chicken population. The QTL for 12 traits
      (i.e. body weight (BW), six for egg character, three for egg shell colour and two
      for egg production) of chickens were identified. An F2 population comprising 265
      female chickens obtained by crossing White Leghorn and Rhode Island Red breeds
      and genotyped for 123 microsatellite markers was used for detecting QTL. Ninety
      six markers were mapped on 25 autosomal linkage groups, and 13 markers were
      mapped on one Z chromosomal linkage group. Eight previous unmapped markers were
      assigned to their respective chromosomes in this study. Significant QTL were
      detected for BW on chromosomes 4 and 27, egg weight on chromosome 4, the short
      length of egg on chromosome 4, and redness of egg shell colour (using the L*a*b*
      colour system) on chromosome 11. A significant QTL on the Z chromosome was linked
      with age at first egg. Significant QTL could account for 6-19% of the phenotypic
      variance in the F2 population.

PMID- 15147390
TI  - A first-generation microsatellite linkage map of the Japanese quail.
AB  - A linkage map of the Japanese quail (Coturnix japonica) genome was constructed
      based upon segregation analysis of 72 microsatellite loci in 433 F(2) progeny of
      10 half-sib families obtained from a cross between two quail lines of different
      genetic origins. One line was selected for long duration of tonic immobility, a
      behavioural trait related to fearfulness, while the other was selected based on
      early egg production. Fifty-eight of the markers were resolved into 12 autosomal
      linkage groups and a Z chromosome-specific linkage group, while the remaining 14
      markers were unlinked. The linkage groups range from 8 cM (two markers) to 206 cM
      (16 markers) and cover a total map distance of 576 cM with an average spacing of
      10 cM between loci. Through comparative mapping with chicken (Gallus gallus)
      using orthologous markers, we were able to assign linkage groups CJA01, CJA02,
      CJA05, CJA06, CJA14 and CJA27 to chromosomes. This map, which is the first in
      quail based solely on microsatellites, is a major step towards the development of
      a quality molecular genetic map for this valuable species. It will provide an
      important framework for further genetic mapping and the identification of
      quantitative trait loci controlling egg production and fear-related behavioural
      traits in quail.

PMID- 15147391
TI  - Verification of selective DNA pooling methodology through identification and
      estimation of the DGAT1 effect.
AB  - The discovery of markers linked to genes that are responsible for traits of
      interest to the dairy industry might prove useful because they could aid in
      selection and breeding decisions. We have developed a selective DNA pooling
      methodology to allow us to efficiently screen the bovine genome in order to find
      genes responsible for production traits. Using markers on chromosome 14 as a test
      case, we identified a gene (DGAT1) previously known to affect three traits (fat
      yield, protein yield and total milk yield). Furthermore, we predicted similar
      effects to those previously shown for DGAT1 in a New Zealand Holstein-Friesian
      herd. Additionally, we showed a low error rate (1.6%) for the pooling procedure.
      Hence we are confident that we can apply this procedure to an entire genome scan
      in the search for quantitative trait loci (QTL).

PMID- 15147392
TI  - Evidence for quantitative trait loci affecting twinning rate in North American
      Holstein cattle.
AB  - Twinning in dairy cattle has been associated with many negative health and
      reproductive events that cause economic loss to the producer. Reports have
      suggested that twinning rates are increasing and that there may be a positive
      relationship between milk production and twinning frequency. Putative
      quantitative trait loci (QTL) for twinning and ovulation rate on bovine
      chromosomes 5, 7, 19 and 23 have been previously identified in other populations.
      The objective of this study was to detect and possibly confirm the existence and
      effects of these QTL in the North American Holstein population. Half-sib families
      of 20 North American Holstein sires with above average twinning rate predicted
      transmitting abilities (PTA) comprised the sample population under investigation.
      Twinning rate PTA values had been estimated from calving data. DNA extracted from
      semen samples was analysed using 45-61 microsatellite markers across the four
      chromosomes. Marker heterozygosity of the patriarchs averaged 62%. Evidence of
      twinning QTL was found in multiple families on chromosomes 5, 7 and 23 and in one
      family on chromosome 19. Four of the sires formed one three-generation family:
      one sire and three half-sib sons with sons of their own. This extended family was
      analysed with additional markers confirming a twinning QTL of significant size on
      chromosome 5.

PMID- 15147393
TI  - Characterization of open reading frame-expressed sequence tags generated from Bos
      indicus and B. taurus mammary gland cDNA libraries.
AB  - Sequence-based gene expression data are used to interpret results from functional
      genomic and proteomics studies. Although more than 300 000 bovine-expressed
      sequence tags (ESTs) are available in public databases, a more thorough and
      directed sampling of the expressed genome is needed to identify new transcripts
      and improve assembly and annotation of existing transcript sequences.
      Accordingly, we examined the utility of constructing cDNA libraries synthesized
      by arbitrarily primed RT-PCR of mRNA from tissues not well represented in the
      publicly available bovine EST database. A total of 33 cDNA libraries were
      constructed from healthy and infected mammary gland tissues of Brazilian Gir and
      Holstein cattle. This series of libraries was used to generate 6481 open reading
      frame-expressed sequence tags (ORESTES) that assembled into 1798 unique sequence
      elements of which, 1157 did not significantly match sequence assemblies available
      in the Bos taurus gene index. However, a total of 264 of these 1157 sequence
      elements aligned with mouse and human expressed sequences demonstrating that
      ORESTES is an effective resource for discovery of novel expressed sequences in
      cattle. Furthermore, comparison of the alignment position of bovine ORESTES
      derived sequence elements to human gene reference sequences suggested that the
      priming events for cDNA synthesis more often occurred at the central portion of a
      transcript, which may have contributed to the relatively high rate of novel
      sequence discovery.

PMID- 15147394
TI  - Impact of candidate sire number and sire relatedness on DNA polymorphism-based
      measures of exclusion probability and probability of unambiguous parentage.
AB  - Genetic paternity testing can provide sire identity data for offspring when
      females have been exposed to multiple males. However, correct paternity
      assignment can be influenced by factors determined in the laboratory and by size
      and genetic composition of breeding groups. In the present study, DNA samples
      from 26 commingled beef bulls and their calves from the Nebraska Reference Herd-1
      (NRH1), along with previously reported Illinois Reference/Resource Families data,
      were used to estimate the impact of sire number and sire relatedness on
      microsatellite-based paternity testing. Assay performance was measured by
      exclusion probabilities and probabilities of unambiguous parentage (PUP) were
      derived. Proportion of calves with unambiguous parentage (PCUP) was also
      calculated to provide a readily understandable whole-herd measure of unambiguous
      paternity assignment. For NRH1, theoretical and observed PCUP values were in
      close agreement (85.3 and 85.8%, respectively) indicating good predictive value.
      While the qualitative effects on PUP values of altering sire number and sire
      relatedness were generally predictable, we demonstrate that the impacts of these
      variables, and their interaction effects, can be large, are non-linear, and are
      quantitatively distinct for different combinations of sire number and degree of
      sire relatedness. In view of the potentially complex dynamics and practical
      consequences of these relationships in both research and animal production
      settings, we suggest that a priori estimation of the quantitative impact of a
      given set of interacting breeding group-specific and assay-specific parameters on
      PUP may be indicated, particularly when candidate sire pools are large, sire
      relatedness may be high, and/or loci numbers or heterozygosity values may be
      limiting.

PMID- 15147395
TI  - Radiation hybrid map assignments of 11 ESTs obtained from a 28-day-old swine
      embryo cDNA library to the IMpRH map.
AB  - In order to improve the map resolution and to locate more genes on the porcine
      radiation hybrid map, expressed sequence tags (ESTs) were isolated from a 28-day
      old normal pig embryo cDNA library. The ESTs were sequenced from the 5'-end and
      similarities were checked with sequences registered in the NCBI DNA database
      (http://www.ncbi.nlm.nih.gov/blast/). The ESTs sequences which have high identity
      scores (>80%) against human genes or ESTs were further sequenced from the 3'
      untranslated region. The ESTs which were sequenced successfully were used to
      design primers for PCR analysis of the radiation hybrid panel. Eleven ESTs were
      physically mapped to porcine chromosomes 2, 4, 8, 10, 13, 14 and X. The
      localizations are in agreement with the comparative mapping data between human
      and pig. The results will provide unique information to the comparative map of
      human and pig.

PMID- 15147396
TI  - cDNA cloning, genomic structure and polymorphism of the porcine FHL3 gene.
AB  - LIM domain proteins are important regulators of the growth, determination and
      differentiation of cells. Four-and-a-half LIM-only protein 3 (FHL3) is a type of
      LIM-only protein that contains four tandemly repeated LIM motifs with an N
      terminal single zinc finger (half LIM motif). In this study, we have determined
      the complete coding sequence of pig FHL3 which encodes a 280 amino acid protein.
      The coding region of the pig FHL3 gene is organized in five exons and spans an
      approximately 2.1-kb genomic region. Comparative sequencing of six pig breeds
      revealed three single nucleotide polymorphisms (SNPs) within exon 2 of which an A
      ->G substitution at position 313 changes a codon for arginine into a codon for
      glycine. The substitution was situated within a PstI recognition site and
      developed as a PCR-RFLP marker for further use in population variation
      investigations and association analysis. The A/G polymorphism was segregating
      only in Landrace pigs. Association studies of the FHL3 polymorphism with carcass
      traits provided preliminary evidence that the PstI PCR-restriction fragment
      length polymorphism (RFLP) genotype may be associated with variation in several
      carcass traits of interest for pig breeding. Further investigations in more
      Landrace pigs are needed to confirm this.

PMID- 15147397
TI  - Mapping and transcription profiling of CASP1, 3, 6, 7 and 8 in relation to
      caspase activity in the bovine cumulus-oocyte complex.
AB  - So far 12 caspases have been described in mouse and human while only one (CASP13)
      is known in cattle. The aim of this study was to (1) search for other bovine
      caspases by reverse transcription and polymerase chain reaction (RT-PCR) and (2)
      examine the presence of bovine caspase mRNA and active protein in the cumulus
      oocyte complex. Five caspases (1, 3, 6, 7 and 8) were identified, partially
      cloned and sequenced. Four of them were mapped. Differential transcription of the
      caspase genes was detected, but no active caspase protein was found in diverse
      bovine oocytes. Cumulus granulosa cells (CGC) contain CASP1, 6, 7 and 8 mRNA and
      active caspase protein. The presence of caspase mRNA and active caspase proteins
      in CGCs suggests the occurrence of apoptosis in cumulus-oocyte complex, while
      caspase activation is blocked in fresh oocytes and therefore caspase
      transcription cannot be used to predict the oocyte developmental capacity.

PMID- 15147398
TI  - Investigation of a peroxisome proliferator-activated receptor gamma haplotype
      effect on meat quality and carcass traits in pigs.
AB  - Peroxisome proliferator-activated receptor gamma (PPARG) is a key transcription
      factor that controls adipocyte differentiation and fat deposition in mammals. The
      primary goal of this study was to investigate PPARG as a candidate gene for meat
      quality and carcass traits in swine. Part of the PPARG promoter, along with the
      most 5'-proximal exon of the gene, was amplified by PCR and subsequently screened
      for polymorphisms by sequencing. A Met59Val substitution was detected in the
      porcine PPARG gene along with four polymorphisms in the promoter region of the
      adipose-specific PPARG2. Three of these polymorphisms were chosen for genotyping
      and tested for association with meat quality, carcass and growth traits,
      according to the candidate gene approach. More than 1500 animals from different
      lines and populations were used in the study with records for meat quality and
      carcass traits. No convincing associations were found between the traits
      investigated and the PPARG genotypes. It does not appear that variation at the
      PPARG locus is affecting meat quality, carcass or growth traits in the pig
      populations studied.

PMID- 15147399
TI  - Mapping of the porcine oestrogen receptor 2 gene and association study with
      litter size in Iberian pigs.
AB  - Genes encoding the oestrogen receptors (ESR) are considered candidate genes for
      prolificacy traits due to the key role these molecules play in the regulation of
      reproductive physiology. In this paper, we report the assignment of the pig ESR2
      gene to porcine chromosome 1 by radiation hybrid mapping. Most of the ESR2 cDNA
      was sequenced from Iberian pig ovarian RNA samples and one A/G single nucleotide
      polymorphism (SNP) was found at exon 5, being associated with a Met/Val
      substitution at position 949. This SNP was genotyped using a PCR-RFLP (Hsp92II)
      protocol and its potential effect on litter size was evaluated in two Iberian pig
      populations. However, no statistically significant association between the ESR2
      polymorphism and litter size was found.

PMID- 15147400
TI  - Assignment of the fatty acid Coenzyme A ligase, long chain 2 (FACL2) gene to
      porcine chromosome 15.

PMID- 15147401
TI  - Linkage mapping of NPY to bovine chromosome 4.

PMID- 15147402
TI  - Male-specific SRY and ZFY haplotypes in US beef cattle.

PMID- 15147403
TI  - Assignment of 10 canine genes to the canine linkage and comparative maps.

PMID- 15147404
TI  - Radiation hybrid mapping of two members of the Toll-like receptor gene family in
      pigs.

PMID- 15147405
TI  - Seven bacterial artificial chromosome-derived canine microsatellite-linking
      physical and genetic maps.

PMID- 15147406
TI  - PCR-RFLPs, linkage and RH mapping of the porcine TGFB1 and TGFBR1 genes.

PMID- 15147407
TI  - Characterization of five single nucleotide polymorphisms in the porcine stearoyl
      CoA desaturase (SCD) gene.

PMID- 15147408
TI  - Linkage mapping of Microphthalmia-associated transcription factor to cattle
      chromosome 22.

PMID- 15147409
TI  - Mapping of the porcine JAK2, JAK3 and TYK2 genes using somatic cell and radiation
      hybrid panels.

PMID- 15147411
TI  - Partial molecular characterization and mapping of the GDF9 gene to porcine
      chromosome 2.

PMID- 15147410
TI  - Chromosomal localization of CTSL: expanding of the region of evolutionary
      conservation between GGAZ and HSA9.

PMID- 15147412
TI  - Molecular characterization and mapping of the canine KRAB zinc finger gene
      ZNF331.

PMID- 15147413
TI  - Linkage mapping of ovine cysteine and histidine-rich protein gene (CYHR1) to
      chromosome 9.

PMID- 15147414
TI  - Cancer after renal transplantation: the next challenge.

PMID- 15147415
TI  - Pharmacogenomics and transplantation: where are we?

PMID- 15147416
TI  - An eye to quality.

PMID- 15147417
TI  - Memory T cells in transplantation: generation, function, and potential role in
      rejection.
AB  - The adaptive immune system is endowed with long-lived memory to recall previous
      antigen encounters and respond more effectively to them. Memory immune responses
      are mediated by antigen-specific memory T lymphocytes that exhibit enhanced
      function compared with naive T cells that have never encountered antigen. While
      the generation of memory T cells specific for pathogens is beneficial in
      providing protective immunity, memory T cells specific for alloantigens can be
      deleterious to the recipient of a transplanted organ. In graft rejection, memory
      T cells mediate accelerated, "second-set" rejection and their presence has been
      associated with increased propensity for early rejection. Recent findings have
      demonstrated that alloreactive memory T cells can be generated via exposure to
      alloantigens, as well as stimuli that are cross-reactive with alloantigens, and
      are therefore likely present in "naive" individuals. This review focuses on the
      characteristics of memory T cells which make them of special interest to the
      transplant community, including differential activation requirements, broad
      homing properties, and resistance to tolerance induction. The multiple ways in
      which memory T cells can contribute to early and late graft rejection are
      discussed, as well as potential targets for combating alloreactive memory to be
      considered in the future design of tolerance induction strategies.

PMID- 15147418
TI  - Arraying the orchestration of allograft pathology.
AB  - Microarrays, or gene chips, are exciting investigative tools for analyzing
      expression changes across thousands of genes in concert in tissues and cells of
      interest. Despite the relatively recent application of microarrays to transplant
      research, they hold great promise for unraveling the staging of rejection,
      stratifying patients towards more individualized treatment regimes, and
      discovering noninvasive biomarkers for monitoring of intragraft events.
      Bioinformatics tools are being developed to sift through the large data sets
      generated as "genomic fingerprints" of the underlying biologic pathways. Gene
      clustering and class prediction tools allow discovery of diagnostic and
      prognostic molecular signatures of health and disease. Oligonucleotide-based
      microarrays also have utility in genotyping polymorphic markers. This report
      reviews the current literature of microarray use in transplantation research,
      compares currently available array platforms, and discusses future application of
      this technology to clinical organ transplantation.

PMID- 15147419
TI  - FTY720 prevents anti-CD4 mAb-induced tolerance but cannot reverse established
      tolerance in a rat kidney transplantation model.
AB  - FTY720 is highly effective in various models of transplantation and autoimmunity.
      In order to find drugs that act synergistically with a tolerance-inducing
      nondepleting anti-CD4 mAb we studied this combination in a strong DA to LEW
      kidney transplantation model. Rats were treated with 0.3 mg/kg of FTY720 for 14
      days and anti-CD4 mAb RIB5/2, alone or in combination. After kidney
      transplantation serum creatinine and blood lymphocyte counts were monitored.
      Immunohistology, ELISPOT and TaqMan trade mark -PCR analysis of biopsies were
      performed. Short-term application of RIB5/2 but not FTY720 induced long-term
      survival of kidney transplants. Moreover, the combination of FTY720 + RIB5/2
      prevented tolerance induction. In the combination group serum creatinine levels
      increased 1 week after cessation of therapy and all rats died from uremia within
      72 days. Intragraft immunohistology, ELISPOT and real-time RT-PCR analysis at day
      21 demonstrated an enhanced T-cell infiltration and activation but a diminished
      up-regulation of protective genes in the grafts from recipients receiving the
      combination therapy. In contrast, delayed application of FTY720 to RIB5/2-treated
      rats did not interact with RIB5/2-induced tolerance. In summary, FTY720 is
      powerful in preventing intragraft infiltration by naive T cells but this might
      also affect the early development of graft-protecting regulatory T cells and
      tolerance induction.

PMID- 15147420
TI  - CD4+ T cells prevent skin autoimmunity during chronic autologous graft-versus
      host-disease.
AB  - CD4 regulatory cells have been postulated to prevent autologous graft-vs.-host
      disease (GVHD). In order to test this hypothesis, we used BALB/c mice, a strain
      known to be resistant to autologous GVHD, which had received autologous stem cell
      transplantation (ASCT) and cyclosporine A (CsA). As expected, ASCT/CsA-treated
      BALB/c mice did not develop any sign of acute or chronic GVHD. However, depletion
      of CD4 T cells induced a skin disease with clinical and histological features of
      alopecia areata (AA), a CD8 T-cell-mediated human autoimmune skin disease. The
      hair loss in mice developing AA was associated with the infiltration of the skin
      by activated CD8 T cells. Analysis of the T-cell recovery in ASCT- and ASCT/CsA
      treated mice showed that CsA induced an increase in the number of CD4+ 25+ T
      cells, suggesting that the lack of GVHD in ASCT/CsA treated-mice could be related
      to the expansion of this CD4 T-cell subset. Collectively these data show that CD4
      T cells comprise regulatory cells controlling the onset of autologous GVHD and
      suggest that the naturally occurring CD4+ 25+ subset may be responsible for this
      effect.

PMID- 15147421
TI  - Improved hepatic regeneration with reduced injury by redox factor-1 in a rat
      small-sized liver transplant model.
AB  - Redox factor-1 (Ref-1) has been shown to function in a redox-dependent manner in
      the cell. This study was designed to examine the effects of Ref-1 on liver
      regeneration as well as protection against postischemic injury in a rat model of
      20% partial liver transplantation. Adenovirus carrying the full length of Ref-1
      gene was introduced into liver grafts by ex vivo perfusion via the portal vein
      during preservation. Liver graft weights were assessed, as well as graft
      histology, serum levels of alanine aminotransferase (ALT)/bilirubin, DNA binding
      activities of AP-1 and Stat3. Redox factor-1 successfully expressed in the liver
      graft, improved regeneration by promoting cell proliferation. Overexpression of
      Ref-1 protein also reduced post-transplant injury and inflammatory reactions in
      the grafts. The increased serum levels of ALT and bilirubin observed after
      transplantation were significantly reduced by Ref-1 overexpression. Furthermore,
      adenovirally overexpressed Ref-1 in mouse liver successfully promoted liver
      regeneration after simple partial hepatectomy. Interestingly, Ref-1 significantly
      increased DNA binding of Stat3, but not AP-1. Overexpressed Ref-1 effectively
      promoted graft regeneration and reduced postischemic injury in a small-sized
      liver transplantation model. The results of the present study may open a new
      avenue to clinical transplantation of disproportionately sized grafts in living
      related liver transplantation.

PMID- 15147422
TI  - Is ischemic preconditioning a useful strategy in steatotic liver transplantation?
AB  - This study examined the effect of preconditioning on steatotic livers for
      transplantation and attempted to identify the underlying protective mechanisms.
      Blood flow alterations, neutrophil accumulation, tumor necrosis factor alpha
      release and lipid peroxidation were observed in nonsteatotic livers after
      transplantation. Steatotic and nonsteatotic liver grafts were similar in their
      blood flow, neutrophil accumulation, and TNF release after transplantation.
      However, in the presence of steatosis, lipid peroxidation and hepatic injury
      increased. In addition, recipients of steatotic liver grafts were more vulnerable
      to lung damage associated with transplantation. The conversion of xanthine
      dehydrogenase to xanthine oxidase and the accumulation of xanthine during cold
      ischemia was greater in steatotic than in nonsteatotic liver grafts. The results
      obtained with xanthine oxidase inhibitors indicated that xanthine/xanthine
      oxidase could be responsible for the increased lipid peroxidation as well as the
      exacerbated liver and lung damage associated with transplantation of steatotic
      livers. Preconditioning reduced the xanthine accumulation and percentage of
      xanthine oxidase seen in steatotic liver grafts during cold ischemia, and
      conferred protection against liver and lung damage following transplantation. The
      benefits of preconditioning could be mediated by nitric oxide. These findings
      suggest that preconditioning could be a relevant new strategy to protect against
      the inherent risk of steatotic liver failure following transplantation.

PMID- 15147423
TI  - Ultrastructural changes of rat cardiac myocytes in a time-dependent manner after
      traumatic brain injury.
AB  - We suggest an ultrastructural scoring system to evaluate the degree of damage in
      a time-dependent manner in cardiac myocytes after traumatic brain injury (TBI).
      Forty Wistar-Albino female rats weighing 170-200 g were randomly allocated into
      five groups. Group 1 was the control and Group 2 was the sham-operated group.
      Group 3, Group 4 and Group 5 were trauma groups. Weight-drop technique was used
      for achieving TBI. Lipid peroxidation was estimated by thiobarbituric acid test.
      An electron microscopic scoring model was used to grade the subcellular changes.
      Results of heart injury score (HIS) showed that the 24-h trauma group had
      statistically significant levels in nuclear damage compared with the other groups
      (p < 0.05). Sarcoplasmic reticulum and mitochondria scores of all trauma groups
      were significantly different from the control and sham groups (p < 0.05). The
      results showed that lipid per oxidation levels were statistically significant
      different between the control and all trauma groups (p < 0.05). The electron
      microscopic scoring model worked well in depicting the traumatic changes, which
      were supported by lipid peroxidation levels. Traumatic brain injury produced
      obvious gradual damage on the ultrastructure of the cardiac myocytes and this
      damage was more significant in the 24-h trauma group.

PMID- 15147424
TI  - Cancer after kidney transplantation in the United States.
AB  - Previous reports of cancer after kidney transplantation have been limited by
      small numbers of patients in single-center studies and incomplete ascertainment
      of cases in large registries. We examined rates of malignancies among first-time
      recipients of deceased or living donor kidney transplantations in 1995-2001 (n =
      35 765) using Medicare billing claims. For most common tumors, e.g. colon, lung,
      prostate, stomach, esophagus, pancreas, ovary and breast, cancer rates were
      roughly twofold higher after kidney transplantation compared with the general
      population. Melanoma, leukemia, hepatobiliary tumors, cervical and vulvovaginal
      tumors were each approximately fivefold more common. Testicular and bladder
      cancers were increased approximately threefold, while kidney cancer was
      approximately 15-fold more common. Kaposi's sarcoma, non-Hodgkin's lymphomas, and
      nonmelanoma skin cancers were more than 20-fold increased than in the general
      population. Compared with patients on the waiting list, several tumors were more
      common after transplantation (p < 0.01): nonmelanoma skin cancers (2.6-fold),
      melanoma (2.2-fold), Kaposi's sarcoma (9.0-fold), non-Hodgkin's lymphoma (3.3
      fold), cancer of the mouth (2.2-fold), and cancer of the kidney (39% higher). The
      rates for most malignancies are higher after kidney transplantation compared with
      the general population. Cancer should continue to be a major focus of prevention
      in kidney transplantation.

PMID- 15147425
TI  - The influence of pharmacogenetics on the time to achieve target tacrolimus
      concentrations after kidney transplantation.
AB  - Previously, we reported that, at 3 months after renal transplantation,
      individuals with CYP3AP1 genotype CYP3AP1*1 (linked to CYP3A5*1 and strongly
      associated with expression of CYP3A5) required twofold higher doses of tacrolimus
      to achieve target blood concentrations than individuals with the genotype
      CYP3AP1*3/*3 (CYP3A5 nonexpressors). This study assesses the relationship between
      concentration-controlled dosing during the early period after transplantation,
      the time to achieve target concentrations and genotype in 178 renal transplant
      recipients (CYP3AP1*1/*3 or *1/*1: n = 53, CYP3AP1*3/*3: n = 125). Patients with
      CYP3AP1*1/*3 or *1/*1 had lower mean tacrolimus concentrations during the first
      week (Median 13.5 vs. 18.5 microg/L, p < 0.0001) with significant delay in
      achieving target concentrations (15-20 microg/L during week 1, then 10-15
      microg/L). More CYP3AP1*3/*3 patients had tacrolimus concentrations above target
      during the first week (73.6% vs. 35.8%, p = 0.003). There was no difference in
      the rate of biopsy-confirmed acute rejection, but rejection occurred earlier in
      the CYP3AP1*1/*3 or *1/*1 group (median 7 d vs. 13 d, p = 0.005). In conclusion,
      an initial dosing regimen for tacrolimus based on knowledge of the CYP3AP1
      genotype and subsequently guided by concentration measurements has the potential
      to increase the proportion of patients achieving target blood concentrations
      early after transplantation.

PMID- 15147426
TI  - Association of center volume with outcome after liver and kidney transplantation.
AB  - Outcomes for certain surgical procedures have been linked with volume: hospitals
      performing a high number of procedures demonstrate better outcomes than do low
      volume centers. This study examines the effect of volume on hepatic and renal
      transplant outcomes. Data from the Scientific Registry of Transplant Recipients
      were analyzed for transplants performed from 1996-2000. Transplant centers were
      assigned to volume quartiles (kidney) or terciles (liver). Logistic regression
      models, adjusted for clinical characteristics and transplant center clustering,
      demonstrate the effect of transplant center volume quantile on 1-year post
      transplant patient mortality (liver) and graft loss (kidney). The unadjusted rate
      of renal graft loss within 1 year was significantly lower at high volume centers
      (8.6%) compared with very low (9.6%), low (9.9%) and medium (9.7%) volume centers
      (p = 0.0014). After adjustment, kidney transplant at very low [adjusted odds
      ratio (AOR) 1.22; p = 0.043) and low volume (AOR 1.22 p = 0.041) centers was
      associated with a higher incidence of graft loss when compared with high volume
      centers. Unadjusted 1-year mortality rates for liver transplant were
      significantly different at high (15.9%) vs. low (16.9%) or medium (14.7%) volume
      centers. After adjustment, low volume centers were associated with a
      significantly higher risk of death (AOR 1.30; p = 0.0036). There is considerable
      variability in the range of failure between quantiles after kidney and liver
      transplant. Transplant outcomes are better at high volume centers; however, there
      is no clear minimal threshold volume.

PMID- 15147427
TI  - Cytomegalovirus prophylaxis and graft outcome in solid organ transplantation: a
      collaborative transplant study report.
AB  - We investigated relationships between cytomegalovirus (CMV) seropairing and CMV
      prophylaxis on graft outcome in recipients of solid organ transplants.
      Transplants carried out from 1985 to 2002 and reported to the Collaborative
      Transplant Study were analyzed. In cadaver kidney recipients, CMV prophylaxis was
      significantly associated with improved graft survival only in the seronegative
      recipient/seropositive-donor combination (at 3 years: 79.4% with prophylaxis vs.
      73.5% without prophylaxis; RR 0.80, p < 0.0001). Among patients who had a
      functioning graft at 1 year, significantly fewer patients who received CMV
      prophylaxis received rejection treatment in the preceding year (26.3%), compared
      with patients who did not receive prophylaxis (32.4%) (p = 0.0001), suggesting an
      inhibitory effect of CMV prophylaxis on acute rejection. Significant improvements
      in graft survival after CMV prophylaxis were found also in CMV-negative
      recipients of CMV-positive heart, and lung or heart-lung transplants, but not
      liver transplants. The age of the recipient had a differential effect on graft
      and patient survival after CMV prophylaxis. Use of antilymphocyte antibodies or
      mycophenolate mofetil was not associated with an enhanced CMV effect on graft
      outcome. These results may contribute to a better understanding of the influence
      of pretransplant CMV serology on the effect of CMV prophylaxis.

PMID- 15147428
TI  - Conversion from cyclosporine to tacrolimus improves quality-of-life indices,
      renal graft function and cardiovascular risk profile.
AB  - Long-term use of cyclosporine after renal transplantation results in
      nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be
      more favorable in this respect. In this randomized controlled study in 124 renal
      transplant patients, the effects of conversion from cyclosporine to tacrolimus on
      renal function, cardiovascular risk factors, and perceived side-effects were
      investigated after a follow-up of 2 years. After conversion from cyclosporine to
      tacrolimus renal function remained stable, whereas continuation of cyclosporine
      was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157
      +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus
      resulted in a sustained reduction in systolic and diastolic blood pressure, and a
      sustained improvement in the serum lipid profile, leading to a reduction in the
      Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally,
      conversion to tacrolimus resulted in decreased scores for occurrence of and
      distress due to side-effects. In conclusion, conversion from cyclosporine to
      tacrolimus in stable renal transplant patients is beneficial with respect to
      renal function, cardiovascular risk profile, and side-effects. Therefore, for
      most renal transplant patients tacrolimus will be the drug of choice when long
      term treatment with a calcineurin inhibitor is indicated.

PMID- 15147429
TI  - Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin
      sirolimus combination.
AB  - A single-center cohort study of kidney and kidney-pancreas recipients was
      conducted to evaluate the association between new immunosuppressive regimens and
      risk of thrombotic microangiopathy (TMA). From January 1st,1996 to December 31,
      2002, 368 patients received a kidney or kidney-pancreas transplant at our center.
      Four immunosuppressive regimens were evaluated as potential risk factors of TMA:
      cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA +
      SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus
      (FK + SRL). Thirteen patients developed biopsy-proven TMA in the absence of
      vascular rejection. The incidence of TMA was significantly different in the four
      immunosuppressive regimens studied (p < 0.001). The incidence of TMA was highest
      in the CsA + SRL group (20.7%). The relative risk of TMA was 16.1 [95% confidence
      interval (CI): 4.3-60.8] for patients in the CsA + SRL group as compared with
      those in the FK + MMF group. We also investigated in vitro the pathophysiological
      basis of this association. The CsA-SRL combination was found to be the only
      regimen that concomitantly displayed pro-necrotic and anti-angiogenic activities
      on arterial endothelial cells. We propose that this combination concurs to
      development of TMA through dual activities on endothelial cell death and repair.

PMID- 15147430
TI  - Sirolimus-based therapy following early cyclosporine withdrawal provides
      significantly improved renal histology and function at 3 years.
AB  - Graft function and histology are predictive of renal transplant survival. The
      Rapamune Maintenance Regimen study demonstrated that early cyclosporine (CsA)
      withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen improved renal
      function and blood pressure. We report the protocol-mandated biopsy findings from
      that study. Renal transplant patients (n = 430) receiving SRL-CsA-ST were
      randomized at 3 months after transplantation to remain on SRL-CsA-ST, or to have
      CsA withdrawn (SRL-ST group). Protocol-mandated biopsies were performed at
      engraftment and at 12 and 36 months. Two pathologists blindly evaluated 484
      biopsies to obtain the Chronic Allograft Damage Index (CADI) scores. At 36 months
      among patients with serial biopsies (n = 63), the mean CADI score was
      significantly lower with SRL-ST(4.70 vs. 3.20, p = 0.003), as was the mean
      tubular atrophy score (0.77 vs. 0.32, p < 0.001). All six components of the CADI
      score were numerically lower in SRL-ST group; moreover, inflammation and the
      tubular atrophy scores decreased significantly in the SRL-ST group between 12 and
      36 months. The calculated glomerular filtration rate at 36 months was
      significantly better in the CsA-withdrawal group (54.8 vs. 68.2 mL/min, p =
      0.009). In conclusion, withdrawing CsA from the SRL-CsA-ST regimen resulted in
      improved renal histology and function.

PMID- 15147431
TI  - Immune and nonimmune predictors of cardiac allograft vasculopathy onset and
      severity: multivariate risk factor analysis and role of immunosuppression.
AB  - We studied 361 patients, to evaluate risk factors for cardiac allograft
      vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT).
      Rejection scores (RS) on endomyocardial biopsy were calculated (first year and
      whole follow-up). CAV onset was defined as any lesion seen at yearly angiography.
      A CAV severity/diffusion index was calculated for each patient summing up the
      scores of all lesions. Cox multivariate analysis included: donor age, sex, and
      weight; recipient sex, age, pre-HT diagnosis, hypertension, diabetes and
      hyperlipidemia post-HT; number of treated rejections and RS; and
      immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year,
      22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p
      < 0.0001, relative risk (RR) = 9.9], male donor (p < 0.001, RR = 3.2), high RS
      for severe (> or = 3A) grades (p < 0.02, RR = 2.01), high cyclosporine at 3
      months (p < 0.02, RR = 1.9). Risk factors for CAV severity/diffusion were higher
      donor weight (p < 0.01, RR = 7.5), high prednisone dosage at 1 year (p < 0.0001,
      RR = 21.1), and coronary disease pre-HT (p < 0.002, RR = 9.7). High RS was an
      independent predictor for CAV onset, not severity/diffusion. This suggests an
      immune basis for CAV onset and nonimmune modulation for progression. High RS for
      severe grades may provide a predictor for patients at risk.

PMID- 15147432
TI  - Early graft function after living donor kidney transplantation predicts rejection
      but not outcomes.
AB  - Poor early graft function (EGF) after deceased donor kidney transplantation
      (DDKT) has been intensely studied. Much less is known about poor EGF after living
      donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed
      between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated
      with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The
      incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR
      2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p =
      0.0025) emerged as independently associated with poor EGF. Neither functional
      graft survival nor 1-year graft function differed among the EGF groups. However,
      DGF and SGF strongly predisposed to acute rejection (AR), which compromised
      functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we
      conclude that diabetic etiology of renal disease and WIT are the dominant risk
      factors for poor EGF after LDKT. Poor EGF did not directly compromise functional
      graft survival but strongly predisposed to AR. We suggest that immunosuppression
      should be intensified in the poor EGF setting to maximize LDKT longevity, as AR
      does impair functional graft survival.

PMID- 15147433
TI  - Outcome at 3 years with a prednisone-free maintenance regimen: a single-center
      experience with 349 kidney transplant recipients.
AB  - Historically, late steroid withdrawal after kidney transplants has been
      associated with an increased rejection rate. Recently, low rejection rates have
      been reported for recipients treated with complete avoidance or rapid elimination
      of steroids. However, follow-up has been short. We herein report on 3-year
      outcome in recipients whose prednisone was rapidly eliminated and who were
      maintained on a steroid-free regimen. From 10/1/1999 through 5/1/2003, 349
      recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with
      polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either
      mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone.
      Actuarial 3-year patient survival was 95%; graft survival, 93%. Acute rejection
      free graft survival at 1 year was 94%; at 3 years, 92%. There was no difference
      between LD and CAD. At 2 years, the mean (+/- SE) serum creatinine level for LDs
      was 1.6 +/- 0.5 mg/dL; for CAD, 1.6 +/- 0.4 mg/dL. We have no new cases of PTLD
      or avascular necrosis; 22 recipients (6%) developed CMV. Currently, 84% of
      recipients remain prednisone-free. We conclude that excellent 3-year patient and
      graft survival can be achieved without maintenance prednisone. With such a
      protocol, steroid-related side-effects are minimal.

PMID- 15147434
TI  - fluvastatin prevents cardiac death and myocardial infarction in renal transplant
      recipients: post-hoc subgroup analyses of the ALERT Study.
AB  - Renal transplant recipients have a greatly increased risk of premature
      cardiovascular disease. The ALERT study was a multicenter, randomized, double
      blind, placebo-controlled trial of fluvastatin (40-80 mg/day) in 2102 renal
      transplant recipients followed for 5-6 years. The main study used a composite
      cardiac end-point including myocardial infarction, cardiac death and cardiac
      interventions. Although reduced by fluvastatin, this primary end-point failed to
      achieve statistical significance thus precluding analysis of predefined
      subgroups. Therefore, in the present survival analysis, we used an alternative
      primary end-point of cardiac death or definite nonfatal myocardial infarction (as
      used in other cardiac outcome trials) which was significantly reduced by
      Fluvastatin therapy and permits subgroup analysis. Fluvastatin reduced LDL
      cholesterol by 1 mmol/L compared with placebo, and the incidence of cardiac death
      or definite myocardial infarction was reduced from 104 to 70 events (RR 0.65; 95%
      CI 0.48, 0.88; p = 0.005). Fluvastatin use was associated with reduction in
      cardiac death or nonfatal myocardial infarction, which achieved statistical
      significance in many subgroups. The subgroups included patients at lower
      cardiovascular risk, who were younger, nondiabetic, nonsmokers and without pre
      existing CVD. These data support the early introduction of statins following
      renal transplantation.

PMID- 15147435
TI  - Rituximab as treatment for refractory kidney transplant rejection.
AB  - Recent studies have shown that a high density of CD 20+ cells are seen in
      patients who have steroid-resistant rejection episodes. Rituximab is a high
      affinity CD-20 specific antibody that inhibits B-cell proliferation while
      inducing cellular apoptosis. Thus, it is a rational choice for therapy in
      transplantation to abrogate B-cell-mediated events. Twenty-seven patients were
      diagnosed with biopsy-confirmed rejection manifested by thrombotic
      microangiopathy and/or endothelialitis between 2/99 and 2/02 at our institution.
      These individuals were treated with a single dose of rituximab, in addition to
      other therapies, in an effort to reverse their rejection episodes. Twenty-four
      received additional steroids while 22 of the 27 patients were also treated with
      plasmapheresis and antithymocyte globulin (ATG). Only three patients experienced
      graft loss not associated with patient death during the follow-up period (605 +/-
      335.3 days). In the 24 successfully treated patients, the serum creatinine at the
      time of initiating rituximab therapy was 5.6 +/- 1.0 mg/dL and decreased to 0.95
      +/- 0.7 mg/dL at discharge. The addition of rituximab may improve outcomes in
      severe, steroid-resistant or antibody-mediated rejection episodes after kidney
      transplantation.

PMID- 15147436
TI  - Sirolimus-induced angioedema.
AB  - Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use
      in organ transplantation. Its full spectrum of side-effects is yet to be defined.
      We describe herein three cases of SRL-induced angioedema (AE) in African-American
      (AA) primary renal allograft recipients who received SRL in combination with
      mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was
      restarted after a period of discontinuation. The third case presented upon
      initial exposure to the drug. None of the patients was receiving any drug that
      has been previously associated with AE. Complete resolution occurred only after
      SRL was withdrawn. AE has not recurred in any of the patients during a follow-up
      period of up to 21 months. We conclude that AE is a previously unrecognized
      adverse event associated with SRL use. Close monitoring for this side-effect,
      especially in AA patients, is warranted.

PMID- 15147437
TI  - Intrahepatic hepatic vein stenosis after living-related liver transplantation
      treated by insertion of an expandable metallic stent.
AB  - Although the incidence of stenosis and obstruction of the hepatic venous
      anastomosis after right hepatic living-related liver transplantation (LRLT) has
      been found to be higher than after orthotopic liver transplantation (OLT), to the
      best of our knowledge, intrahepatic stenosis of the venous trunk in the early
      period after right hepatic LRLT has never been reported in the literature. A 53
      year-old man who underwent right hepatic LRLT, postoperatively, developed liver
      dysfunction and an increasing amount of ascites, and a Doppler sonogram showed a
      flat waveform and low-flow velocity in the hepatic vein. Based on these findings
      an outflow block was suspected, and a hepatic venogram and manometry revealed
      intrahepatic stenosis of a tortuous hepatic venous trunk and a pressure gradient
      of 14 mmHg at the site of the stenosis. We inserted an expandable metallic stent
      (EMS) at the site of intrahepatic venous stenosis, and its insertion was followed
      by a decrease in pressure gradient. Liver function recovered, and the volume of
      ascitic fluid decreased after placement of the EMS. The results of an analysis of
      the venogram and CT volumetric data suggested that the pathogenesis of the
      stenosis was twisting of the venous trunk during hypertrophy of the liver
      parenchyma.

PMID- 15147438
TI  - Eosinophils and atopic dermatitis.
AB  - In spite of the progress regarding the description of immunological phenomena
      associated with atopic dermatitis (AD), the pathogenesis of this disease still
      remains unclear. The presence of eosinophils in the inflammatory infiltrate of AD
      has long been established. Eosinophil numbers as well as eosinophil granule
      protein levels in peripheral blood are elevated in most AD patients and appear to
      correlate with disease activity. Moreover, eosinophil granule proteins, which
      possess cytotoxic activity, are deposited in the skin lesions. These observations
      indicate a role of eosinophils in the pathogenesis of AD. Furthermore, AD is
      associated with increased production of T helper 2 cytokines including
      interleukin (IL)-5, which specifically acts on eosinophils, resulting in
      accelerated eosinophilopoiesis, chemotaxis, cell activation, and delayed
      apoptosis. Therefore, IL-5 is an interesting target for experimental therapy in
      this inflammatory disorder of the skin. Such studies might result in new insights
      into the pathogenetic role of eosinophils in AD.

PMID- 15147439
TI  - The CREATE project: EU support for the improvement of allergen standardization in
      Europe.

PMID- 15147440
TI  - Diversity of allergy and clinical immunology reunified by training at the EU
      level.

PMID- 15147441
TI  - Venom immunotherapy: aqueous vs aluminium hydroxide adsorbed extracts.

PMID- 15147442
TI  - Objectives of training and specialty training core curriculum in allergology and
      clinical immunology.

PMID- 15147443
TI  - Specific immunotherapy in honeybee venom allergy: a comparative study using
      aqueous and aluminium hydroxide adsorbed preparations.
AB  - BACKGROUND: For the immunotherapy of Hymenoptera venom allergy various
      preparations and treatment protocols are in use. However, controlled studies
      making direct comparisons of the efficacy and safety of different regimens are
      rare. OBJECTIVE: To assess prospectively different venom immunotherapy (VIT)
      protocols using an aqueous or an aluminium hydroxide adsorbed allergen
      preparation for the treatment of honeybee venom (HBV) allergy. METHODS: Sixty
      five HBV allergic patients (42 males, 23 females; aged 17-75 years) with a
      history of systemic anaphylactic reactions (SARs) to honeybee stings were treated
      according to three different regimens. During the incremental phase, patients in
      group A (n = 21) or B (n = 21) received an aqueous preparation according to a
      rush protocol. Patients in group C (n = 23) were treated with conventional
      ("slow") VIT using an aluminium hydroxide adsorbed depot preparation. The
      maintenance dose was 100 microg venom in all groups. Maintenance treatment in
      group A was performed with the aqueous preparation administered every 4 weeks,
      whereas in groups B and C the depot preparation was administered every 8 weeks
      (group B) or every 4 weeks (group C). A sting challenge test with a living
      honeybee was performed in 49 patients, 6-12 months after reaching the maintenance
      dose. Another seven patients were stung accidentally by a honeybee ("field
      sting"). RESULTS: Treatment with the aqueous preparation evoked large local
      reactions more frequently than the depot preparation in the dose increase phase
      [53/693 (7.6%) vs 8/206 (3.9%); P = 0.059] and also in the course of maintenance
      therapy [85/172 (49.4%) vs 58/478 (12.1%); P < 0.001]. During the dose increase
      phase, systemic side-effects seemed to occur more frequently in patients on rush
      VIT with the aqueous preparation compared to patients initially treated with the
      conventional schedule using the depot preparation [13/42 (31.0%) vs 3/23 (13.0%);
      not significant). When re-stung by the culprit insect, SARs were observed in 3/20
      patients (15.0%) in group A, 2/18 (11.1%) in group B and 3/18 (16.7%) in group C
      (not significant). CONCLUSIONS: The aluminium hydroxide adsorbed HBV preparation
      caused fewer large local reactions than the aqueous preparation. The therapeutic
      efficacy of the three treatment protocols did not differ.

PMID- 15147444
TI  - Eosinophil traffic in the circulation following allergen challenge.
AB  - BACKGROUND: Eosinophils contribute to the pathogenesis of asthma and localize to
      the lung after allergen exposure by uncertain mechanisms. METHODS: We used
      intrabronchial instillation of allergen to model the interaction between inhaled
      allergen and the lung. We measured the number of peripheral blood leukocytes and
      the expression of VLA-4 (CD49d), Mac-1 (CD11b) and PSGL-1 (CD162) up to 4 h after
      instillation of allergen into a bronchus of eight atopic asthmatics. For
      controls, we instilled normal saline into a subset of the asthmatic subjects, and
      allergen into nonatopic, nonasthmatic subjects. RESULTS: There were changes of
      total leukocyte number, number of polymorphonuclear leukocytes, lymphocytes,
      monocytes and eosinophils in all three groups (atopic asthmatics instilled with
      allergen, atopic asthmatics instilled with saline, nonatopic nonasthmatic
      subjects instilled with allergen), which were likely related to bronchoscopy.
      However, the decrease of eosinophils was significant only in the atopic
      asthmatics instilled with allergen. The remaining eosinophils in the allergen
      challenged asthmatics were not activated as defined by cell density or change of
      expression of VLA-4, Mac-1 and PSGL-1. CONCLUSIONS: While eosinophils rapidly and
      specifically leave the circulation after allergen challenge of atopic asthmatics,
      the remaining circulating eosinophils are not activated.

PMID- 15147446
TI  - Cytotoxic mechanisms in different forms of T-cell-mediated drug allergies.
AB  - BACKGROUND: Cytotoxic mechanisms are involved in different forms of drug induced
      exanthems. METHODS: Here we compare the killing pathways of CD4+, CD8+ and
      CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from
      maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas
      mediated killing was analysed in cytotoxicity assays against autologous Epstein
      Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and
      natural killer (NK)-target cells. In addition, affected skin lesions and the TCL
      and clones were stained for perforin and FasL-expression. RESULTS: We detected
      perforin and some FasL-mediated killing in all three types of exanthems. Some of
      the drug-specific T-cell clones analysed exerted mainly perforin-, other more
      FasL-mediated killing showing no strict relationship between their perforin- and
      Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the
      generation of cytotoxic T cells, we detected drug-specific CD8+, TCRalphabeta+ T
      cells, which failed to proliferate to drug presentation by antigen presenting
      cells but killed in a drug dependent way. Interestingly, these cells had
      substantial natural killer-like T cell(s) like features as they were CD56+ and
      CD94+ and had the ability to kill the NK-sensitive cell line K562. CONCLUSION:
      Our data underline the important role of cytotoxic mechanisms in different forms
      of drug induced exanthems and suggest that even some T cells with NK-like
      characteristics may be involved in drug hypersensitivity.

PMID- 15147445
TI  - Macrophage mannose receptor in chronic sinus disease.
AB  - BACKGROUND: The role of infectious agents in the onset and maintenance of chronic
      sinus disease is still not fully understood. Macrophage mannose receptor (MMR),
      an innate pattern recognizing receptor, capable of phagocytosis of invaders and
      signal transduction for proinflammatory mechanisms, might be of importance in
      immune interactions in chronic sinus disease. OBJECTIVE: We examined the MMR in
      sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis
      (CS) and nasal polyposis (NPs). METHODS: Surgical samples from patients with
      sinonasal disease were investigated with real-time RT-PCR for quantification of
      MMR mRNA expression, and the presence and location of MMR-positive cells was
      analysed by immunohistochemistry. RESULTS: Quantification of MMR mRNA showed a
      statistically significant higher expression in NPs compared to CS without NP and
      controls. Immunohistochemistry revealed expression of MMR in all tissue samples;
      however, in NP we found an enhanced positive cellular staining including cell
      aggregates. CONCLUSIONS: We could demonstrate for the first time that the
      expression of MMR is significantly upregulated in NP compared to patients with CS
      without NP or turbinate tissue of controls. Macrophages expressing MMR,
      accumulated in cell aggregates in NPs, play a possible key role in pathogen
      macrophage interaction in NP disease.

PMID- 15147447
TI  - Concentrations of domestic mite and pet allergens and endotoxin in Palestine.
AB  - BACKGROUND: A few studies have compared indoor allergens and endotoxin levels
      between urban and rural settings as important determinants for asthma and atopy
      in children. However, no study was done in the Middle East or investigated
      refugee camps. METHODS: As part of a nested case-control study in Ramallah in
      2001, we measured house dust mite and pet allergens, as well as endotoxin in dust
      collected from 110 children's mattresses and living room floors. RESULTS:
      Geometric mean (GM) concentrations of Dermatophagoides pteronyssinus (Der p1)
      antigen were 4.48 microg/g in mattress dust and 1.23 microg/g floor dust. The
      highest Der p1 levels were seen in refugee camps. Concentrations of
      Dermatophagoides farinae antigen (Der f1) were much lower (<0.08 microg/g dust).
      Concentrations of cat allergen (Fel d1) were highest in villages, and those of
      dog allergen (Can f1) were highest in mattresses from cities and in floor dust
      from refugee camps. GM of endotoxin levels were 25.7 EU/mg in mattress dust and
      49 EU/mg dust in floor dust. CONCLUSIONS: Concentrations of Der p1 were high
      compared to Western European countries, but were lower compared to UK and
      Australia. Levels of pet allergens were lower than in Western Europe. Endotoxin
      levels were higher compared to developed countries. Indoor environmental factors
      such as dampness seemed to be important determinants for allergen and endotoxin,
      but living habits such as lack of mattress cover appeared unimportant.

PMID- 15147448
TI  - Allergy, asthma and markers of infections among Albanian migrants to Southern
      Italy.
AB  - BACKGROUND: Studies of immigrants represent an useful tool to determine the
      relative relevance of environmental vs genetic factors in causing the reported
      rapid increase of the prevalence of sensitization and allergic diseases. METHODS:
      A total of 152 Albanian migrants to Southern Italy responded to a questionnaire
      based on the European Community Respiratory Health Survey (ECRHS) and 139 of them
      underwent skin prick test, and 61 serological assays for total IgE and IgG
      antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV-1),
      hepatitis A virus (HAV) and Helicobacter pylori (HP). RESULTS: Reported asthma
      was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152;
      15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%)
      subjects. The frequency of skin sensitization to pollen (P = 0.003) and that of
      hay fever (P = 0.004) increased with the time spent in Apulia. All the 61 sera
      had antibodies against HAV, 59/61 (96.7%) against HSV-1, 48/61 (78.7%) against HP
      and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever
      symptoms were correlated to the duration of residence in Southern Italy.
      CONCLUSIONS: Data presented indicate that Albanian migrants to Italy, in spite of
      the low prevalence of allergic diseases and sensitization in their country of
      origin, manifest with time an increasing prevalence of sensitization to local
      allergens and nasal symptoms after immigration to Italy. This would suggest a
      permanent role of allergen exposure and lifestyle factors in influencing the
      appearance of sensitization and symptoms of allergic diseases.

PMID- 15147449
TI  - Comparison of local risk factors for children's atopic symptoms in Hanoi,
      Vietnam.
AB  - BACKGROUND: A 1999 study in Hanoi, Vietnam using the International Study on
      Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence
      of atopic symptoms. Identifying risk factors for symptoms in these children may
      help in understanding the causes for these high estimates. METHODS: An ISAAC
      questionnaire with supplemental questions on environmental variables was
      distributed to 5495 school children in Hanoi and a suburban district, Dong Anh.
      The response rate was 65.7%. RESULTS: In Dong Anh, the following were among the
      significant age and gender adjusted associations: pig ownership [odds ratio (OR)
      (95% confidence interval), OR = 1.79 (1.18-2.70) for doctor-diagnosed asthma
      (DDA), OR = 1.72 (1.08-2.78) for doctor diagnosed hay fever (DDHF)] and farming
      [OR = 1.67 (1.27-2.19) for ever asthma, OR = 1.51 (1.09-2.09) for DDHF]. In
      multivariate models, tuberculosis (TB) was a significant predictor of atopic
      symptoms [Hanoi: OR = 3.09 (1.10-8.70) for DDA, Dong Anh: OR = 3.71 (1.40-9.84)
      for DDA, OR = 4.66 (1.88-11.57) for DDHF]. CONCLUSIONS: These findings are
      contrary to the "hygiene hypothesis". Recent immunologic and epidemiologic
      studies refute the inverse association between allergy and TB and may be one
      explanation for the positive association in this study. The positive association
      with pig ownership and farming may be because of exposures on farms in a
      developing country that may be different from exposures in farms of developed
      countries.

PMID- 15147450
TI  - The influence of air conditioning, humidity, temperature and other household
      characteristics on mite allergen concentrations in the northeastern United
      States.
AB  - BACKGROUND: Information about the influence of housing and occupant
      characteristics on mite allergen concentrations is crucial to determine which
      methods could be used to decrease exposure of susceptible subjects. OBJECTIVES:
      To identify housing and occupant characteristics that are associated with mite
      allergen concentrations in house dust collected from living rooms and mattresses.
      METHODS: We collected dust samples from 750 homes in the northeastern US. The
      influence of various characteristics on concentrations of mite allergens (Der p 1
      and Der f 1) was studied using multiple linear regression analysis. RESULTS: Some
      characteristics, like absence of air conditioners, the presence of mold or
      mildew, and a lower temperature were consistently associated with higher
      concentrations of both mite allergens in dust from all sampling locations.
      However, none of these factors changed Der p 1 or Der f 1 concentrations by more
      than a factor of 2. People of white ethnic background had roughly two times
      higher mite allergen concentrations, while family income, family size, and
      education level only marginally influenced mite allergen concentrations.
      CONCLUSIONS: Various housing characteristics have some influence on mite allergen
      concentrations, and could possibly be used to decrease exposure of susceptible
      subjects. However, only a limited percentage of the variation in mite allergen
      concentrations was explained by these characteristics.

PMID- 15147451
TI  - IgE antibodies of fish allergic patients cross-react with frog parvalbumin.
AB  - BACKGROUND: The major allergens in fish are parvalbumins. Important
      immunoglobulin (Ig)E cross-recognition of parvalbumins from different fish
      species has been shown. Recently frog parvalbumin alpha has been found to be
      responsible for a case of IgE-mediated anaphylaxis triggered by the ingestion of
      frog meat. The aim of this study was to investigate whether IgE antibodies of
      fish allergic persons cross-react with frog parvalbumin and to appreciate its
      clinical relevance. METHODS: The sera of 15 fish allergic patients and one fish
      and frog allergic patient were tested by IgE-immunoblotting against frog muscle
      extract. Sera were tested against recombinant parvalbumin alpha and beta from
      Rana esculenta. Skin prick tests were performed in selected patients with
      recombinant frog parvalbumin. Ca(2+) depletion experiments and inhibition studies
      with purified cod and frog recombinant parvalbumin were done to characterize the
      cross-reactive pattern. RESULTS: Fourteen of the sera tested had IgE antibodies
      recognizing low molecular weight components in frog muscle extract. Calcium
      depletion experiments or inhibition of patient sera with purified cod parvalbumin
      led to a significant or complete decrease in IgE binding. When tested against
      recombinant parvalbumins, three of 13 sera reacted with alpha parvalbumin and 11
      of 12 reacted with beta parvalbumin from R. esculenta. Skin prick tests performed
      with recombinant frog parvalbumin were positive in fish allergic patients.
      Inhibition studies showed that a fish and frog allergic patient was primarily
      sensitized to fish parvalbumin. CONCLUSION: Cod parvalbumin, a major cross
      reactive allergen among different fish species, shares IgE binding epitopes with
      frog parvalbumin. This in vitro cross-reactivity seems to be also clinically
      relevant. Parvalbumins probably represent a new family of cross-reactive
      allergens.

PMID- 15147452
TI  - Allergen avoidance does not alter airborne cat allergen levels in classrooms.
AB  - BACKGROUND: Some schools in Sweden offer allergen avoidance classrooms for
      allergic children with severe asthma. However, the measures commonly used to
      achieve a reduction in allergen levels have not been properly evaluated. The aim
      of the present prospective study was to study whether the levels of airborne cat
      allergen are altered after introducing feasible intervention measures in
      classrooms, without interfering with peoples' freedom of choice regarding pet
      ownership. METHODS: Twenty-five classes, including five established allergy
      prevention classrooms participated in the study during a school year. After one
      term, six classes underwent a number of intervention measures recommended by the
      Swedish National Institute of Public Health. Curtains, upholstery and plants were
      removed, bookshelves were replaced with cupboards and regular cleaning was
      increased. Airborne dust was collected weekly (32 weeks) using duplicate Petri
      dishes (n = 1574) and on six occasions using two personal air samplers in each
      class (n = 264). RESULTS: Airborne cat allergen levels were showing a similar
      variability throughout the whole study in all classes. Despite extensive measures
      in order to reduce allergen exposure, cat allergen levels were unaltered in the
      six classes after intervention. Allergen levels were not significantly lower in
      the established allergy prevention classes, compared with the other classes. Cat
      allergen levels differed, however, significantly between classes with few and
      many cat owners (P < 0.05). CONCLUSIONS: We conclude that the recommended
      allergen avoidance measures used in this study did not reduce airborne cat
      allergen. It seems plausible that measures that fail to reduce allergen levels
      also fail to influence health status in allergic children but this remains to be
      shown.

PMID- 15147453
TI  - Hepatitis C and urticaria: cause and effect?

PMID- 15147454
TI  - Fatal allergy as a possible consequence of long-term elimination diet.

PMID- 15147455
TI  - Euro coins and contact dermatitis.

PMID- 15147456
TI  - Predominant aeroallergen pollen grains in the atmosphere of Ankara, Turkey.

PMID- 15147457
TI  - Orthopedic and neurological complications of cervical dystonia--review of the
      literature.
AB  - Cervical dystonia is the most frequent form of focal dystonia. Further, cervical
      dystonia can occur as a feature of segmental or generalized dystonias and
      cerebral palsy. Treatment with botulinum toxin to relieve pain and improve
      functional and psychological outcome is effective, but expensive. However,
      pharmacoeconomic studies evaluating treatment and disease costs have not taken
      into consideration the long-term complications of cervical dystonia. Here we
      present a review of the medical literature on orthopedic and neurological
      complications arising from cervical dystonia, including cervical spine
      degeneration, spondylosis, disk herniation, vertebral subluxations and fractures,
      radiculopathies and myelopathies. In summary, complications are more often
      reported in generalized dystonia and cerebral palsy than in focal dystonia. The
      prevalence is not well established, published estimations go from 18 to 41% in
      selected populations. Awareness of the frequent occurrence of complications and
      screening for symptoms of radiculomyelopathy in patients with dystonia is
      essential to avoid irreversible spinal cord damage. Complications of cervical
      dystonia need to be taken into consideration when weighting risks and calculating
      costs of the disease and its treatment.

PMID- 15147458
TI  - Improved CNS tolerability following conversion from immediate- to extended
      release carbamazepine.
AB  - OBJECTIVES: Tolerability of 'narrow therapeutic ratio' (NTR) antiepileptic drugs
      may improve with uniform drug delivery. We determined whether conversion from
      immediate-release carbamazepine (IR-CBZ) to extended-release carbamazepine (ER
      CBZ) decreased the incidence of CNS side-effects associated with drug
      concentration oscillations. METHODS: We compared CNS side effects and seizure
      frequency for patients with partial-onset seizures (n = 61) treated with IR-CBZ
      for > or =1 year with conversion to ER-CBZ for > or =1 year. We compared
      tolerability findings with absorption variability of the formulations. RESULTS:
      Incidence of CNS side-effects decreased from 49% during IR-CBZ treatment to 20%
      following conversion to ER-CBZ. Patients also had improved tolerability of high
      doses (> or =1200 mg/day) during ER-CBZ treatment. Pharmacokinetic analysis
      showed absorption and drug concentration were much more variable for the
      immediate-release formulation. CONCLUSIONS: This study suggests that ER-CBZ
      formulations, with smoother drug delivery and less variable absorption, provide
      improved CNS tolerability compared with immediate-release formulations.

PMID- 15147459
TI  - Multiple sclerosis in Nord-Trondelag County, Norway: a prevalence and incidence
      study.
AB  - OBJECTIVE: To calculate the prevalence and incidence of multiple sclerosis (MS)
      in Nord-Trondelag County, Norway. MATERIAL AND METHODS: The study comprised
      everyone diagnosed with MS according to the Poser criteria. On 1 January 2000 a
      total of 208 were identified: 130 women (62.5%) and 78 men (37.5%). We calculated
      the crude and age-adjusted annual incidence rates from 1974 to 1999. RESULTS: The
      prevalence on 1 January 2000 was 163.6 of 100,000, 204.8 of 100,000 for women and
      122.6 of 100,000 for men. The age-adjusted annual incidence increased from 3.9 to
      5.6 per 100,000 from 1974 to 1999; women from 4.6 to 6.3 and men from 2.2 to 4.4.
      After 1984, the incidence among women increased most, peaking at 10.2 per 100,000
      in 1984-88. CONCLUSIONS: MS incidence is increasing in Nord-Trondelag County. The
      prevalence is among the highest ever in Norway.

PMID- 15147460
TI  - Diagnosis of multiple sclerosis: comparison of the Poser criteria and the new
      McDonald criteria.
AB  - OBJECTIVES: A confident and accurate diagnosis of multiple sclerosis (MS) is
      important, but a specific diagnostic test for the disease does not exist. The
      traditional diagnostic criteria of Poser et al. were published in 1983, and
      recently, McDonald et al. recommended new criteria for the diagnosis of MS.
      PATIENTS AND METHODS: In this study these two diagnostic schemes were compared by
      prospectively applying both of them to 76 patients with clinical features
      suggesting a new diagnosis of MS. RESULTS: Using the Poser criteria, 29 patients
      (38%) were classified as clinically definite and 35 patients (46%) as laboratory
      definite MS. According to the new McDonald criteria, MS was diagnosed in 39 (52%)
      patients, 37 patients (48%) had 'possible MS'. All patients with a clinically
      definite MS with the Poser criteria were also given the diagnosis of MS as
      recommended by McDonald et al. Of those 35 patients with laboratory definite MS
      according to Poser et al., four patients could be classified as having MS with
      the McDonald criteria, 89% of them had 'possible MS'. Conversely, 75% of the 39
      patients, who fulfilled the new McDonald criteria for MS were assigned to the
      category of clinically definite MS according to the Poser criteria, and 83% of
      the patients with a 'possible MS' using the McDonald criteria, had a laboratory
      definite MS with the Poser criteria. CONCLUSION: MS according to the McDonald
      criteria was diagnosed more often than 'clinically definite MS' according to
      Poser et al., but combining the categories of clinically and laboratory definite
      MS, the diagnosis of MS could clearly be established more frequently using the
      Poser criteria.

PMID- 15147461
TI  - Interleukin-8 and RANTES levels in patients with relapsing-remitting multiple
      sclerosis (RR-MS) treated with cladribine.
AB  - OBJECTIVE: Chemokines are involved in the pathogenesis of multiple sclerosis. The
      aim of the study was to evaluate the effects of immunosuppressive therapy on
      production of two proinflammatory chemokines--interleukin-8 (IL-8) and RANTES
      (regulated on activation, normal T cell expressed and secreted). MATERIALS AND
      METHODS: Twenty-five patients with relapsing-remitting multiple sclerosis were
      treated with 2-chlorodeoxyadenosine (Cladribine), administered subcutaneously in
      6 cycles repeated every 5 weeks. IL-8 and RANTES levels were measured by the
      enzyme-linked immunoassay (ELISA) method in serum and cerebrospinal fluid (CSF)
      before and after treatment. RESULTS: After Cladribine treatment the levels of IL
      8 decreased significantly in CSF only, whereas the RANTES levels decreased
      significantly both in CSF and serum. CONCLUSION: Our results suggest that
      Cladribine therapy might modify the circulating level of RANTES.

PMID- 15147462
TI  - Subdivision of essential tremor patients according to physiologic
      characteristics.
AB  - OBJECTIVE: To test the effect of different forearm postures on tremor
      characteristics. We hypothesized that changes in tremor characteristics in
      relation to posture can subclassify essential tremor (ET) patients. METHODS:
      Fourteen ET patients were tested while seated and holding a full cup in three
      well-defined arm postures: 15 cm above the armrest, elbow at 90 degrees flexion
      and when the cup was near the mouth. Hand movements were recorded using a
      triaxial accelerometer. Concomitantly, we recorded surface electromyogram (EMG)
      signals from the wrist extensor muscles. Hand acceleration and the primary tremor
      frequency from the power spectrum were calculated for each posture in two
      independent trials. The coherence at the primary tremor frequency between the EMG
      and the accelerometry signals was calculated. RESULTS: ET patients could be
      classified into two groups: ET-1 (nine patients) had position-dependent peak
      frequencies while ET-2 (five patients) had position-independent peak frequencies.
      The latter group had significantly higher coherencies between EMG and
      accelerometry of tremor and insignificantly higher tremor amplitudes compared
      with ET-1. In both groups tremor amplitude increased when the hand was near the
      mouth. CONCLUSION: The results suggest that ET patients can be classified based
      on the position dependence of frequency and other physiologic properties.

PMID- 15147463
TI  - Cerebral atrophy as predictor of cognitive function in old, community-dwelling
      individuals.
AB  - OBJECTIVES: The impact of cortical and subcortical atrophy on cognitive function
      was examined in a sample of older community-dwelling men and women. MATERIAL AND
      METHODS: Magnetic resonance imaging was performed on a sample of 129 individuals
      [age: 68.4 +/- 3.6 years (mean +/- SD), range 64-74 years, 64 women and 65 men,
      Mini-Mental State Examination scores above 23] to assess cortical and subcortical
      atrophy. Participants also performed a number of cognitive tasks, and the
      measures of atrophy were used to predict performance in these tasks. RESULTS: In
      men, frontal cortical atrophy predicted worse performance in word fluency and the
      Stroop test, and occipital cortical atrophy was associated with poor performance
      in motor speed. In women, poor performance in motor speed was associated with
      subcortical atrophy at the level of the caudate nucleus. CONCLUSION: Atrophy in
      certain areas was associated with poor performance in specific cognitive tasks,
      although the amount of explained variance was rather limited in this quite
      homogeneous sample.

PMID- 15147464
TI  - Serotonin 2C receptor gene Cys23Ser polymorphism: a candidate genetic risk factor
      of migraine with aura in Japanese population.
AB  - OBJECTIVES: The goal of this study is to clarify the association between migraine
      and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. MATERIALS
      AND METHOD: This study included 37 individuals with migraine with aura (MWA), 80
      with migraine without aura, 43 with tension type headache (TH) and 360 with
      controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase
      chain reaction-restriction fragment length polymorphism techniques. RESULTS: The
      Ser allele frequency in control subjects is much less than that in Caucasian
      population. The Ser allele frequency in patients with MWA was higher than that in
      control subjects. CONCLUSION: The present study provides that 5HTR2c Cys23Ser
      polymorphism may be associated with MWA in Japanese population.

PMID- 15147465
TI  - Do antiphospholipid antibodies increase the long-term risk of thrombotic
      complications in young patients with a recent TIA or ischemic stroke?
AB  - BACKGROUND: The purpose of our study was to determine the relative risk of
      thrombotic events in young patients with a recent TIA or ischemic stroke and
      positive antiphospholipid antibodies (aPL). METHODS: We included 128 consecutive
      patients aged 18-45 years with a recent TIA or ischemic stroke. All patients
      underwent computed tomography scanning and were screened for cardiovascular risk
      factors, cardiac disorders and large vessel disease. Lupus anticoagulant (LA) was
      screened for by an APTT-based assay and a diluted PT-assay. Anticardiolipin
      antibodies (aCL) were tested by enzyme-linked immunosorbent assay, using
      cardiolipin and anti-human IgG and IgM. Thrombotic events could be TIA, stroke,
      myocardial infarction, deep venous thrombosis or pulmonary embolism. Product
      limit estimates of the time free of TIA or stroke and of the time free of any
      thrombotic event were made. The relative risk was estimated by means of a Cox
      proportional hazards regression model. RESULTS: Of the 128 patients, 22 (17.2%)
      had aPL. The mean follow-up was 3 years and 3 months (range 41 days to 6 yrs).
      The incidence of any thrombotic event per 100 patient years of follow-up was 9.0,
      and the incidence of recurrent stroke or TIA was 7.9. The relative risk of any
      thrombotic event in patients with aPL was 0.9 (95% CI: 0.3-2.4) and for recurrent
      ischemic stroke or TIA 0.7 (95% CI: 0.3-2.2). CONCLUSION: In young patients with
      a recent TIA or ischemic stroke, aPL do not seem to be a strong risk factor for
      recurrent stroke or TIA, nor for other thrombotic complications.

PMID- 15147466
TI  - Load force during manual transport in Parkinson's disease.
AB  - OBJECTIVES: To search for a physiological method for the measurement of upper
      extremity dexterity during activities of daily life in Parkinson's disease (PD).
      MATERIALS AND METHODS: We examined load force output during manual transport in
      seven patients with PD and 10 healthy controls. PD patients were measured in both
      the non-medicated and medicated states. The test movement included two continuous
      sub-movements: an upward-forward transport of an object from the table to the
      stand, and a downward-backward transport of the object from the stand to the
      table. Hand movements were recorded using an optoelectronic camera, and load
      force was measured using a force sensor installed in the test object. RESULTS:
      Compared with the controls, PD patients had a different pattern of load force
      output characterized by slower force development and release, lower peak force,
      and less dynamic force generation during movement. After medication, the speed of
      force development and the level of peak force increased in the patients.
      CONCLUSIONS: These findings suggest that PD impairs the production of
      preprogrammed movements. The movements observed in the PD patients may result
      from compensatory strategies relying more on feedback mechanisms.

PMID- 15147467
TI  - Cerebral venous sinus thrombosis manifesting as bilateral subdural effusion.
AB  - Three patients with bilateral subdural effusion, an exclusive manifestation of
      cerebral venous sinus thrombosis (CVST), are presented. A possible explanation of
      this rare occurrence is provided, and the differential therapeutic strategies are
      discussed. We propose to consider CVST in cases of subdural effusions of obscure
      origin. Appropriate imaging studies should not be delayed if there is suspicion
      of sinus thrombosis to enable adequate therapy to be started as soon as possible.

PMID- 15147468
TI  - Spinal reflexes by ultrasound.

PMID- 15147470
TI  - Clinical efficacy of gabapentin for paroxysmal symptoms in multiple sclerosis.

PMID- 15147473
TI  - Support for family carers who care for an elderly person at home - a systematic
      literature review.
AB  - Family carers are a major source of help and assistance to the persons they
      provide care for. They are also major contributors to the welfare system,
      balancing the national health care expenditure. Increasing attention, in research
      as well as government policy, is being paid to their role as informal caregivers.
      Support to family carers seems to be a new 'buzzword' in Swedish Government
      policy. However, supporting family carers may prove to be a more complex
      endeavour than one initially might be led to believe. Support could here be
      understood as any services, assistances, education, information, attitudes, and
      lay or professional person's provision for the benefit of the family carer. The
      aim of this systematic review was to identify modes of, and scientific evidence
      on, support for family carers of cohabiting elderly persons. The method followed
      a seven-step model: a focused research question was formulated creating a base
      for deriving search words and inclusion and exclusion criteria for studies.
      Systematic database searches identified several studies some of which were
      retrieved, critically appraised and classified by two independent reviewers. A
      total of 26 articles were finally included, revealing that family carers fear
      social isolation and wish to network in groups with peers, either for social or
      for learning needs purposes. Family carers also desire respite care. However, it
      is unclear whether they actually benefit from any of the above or how service
      provision should be attempted.

PMID- 15147474
TI  - The willingness to eat. An investigation of appetite among elderly people.
AB  - The aim of this study was to identify and describe factors of importance with
      regard to appetite among elderly people. A qualitative approach was used and the
      method was grounded theory. Fifteen elderly people were interviewed using a
      method with two overall questions. The results show that the willingness to eat
      plays a central role in appetite among elderly people. The appetite is a state on
      a sliding scale, from good to poor appetite. Factors affecting the appetite
      include six categories: mood, personal values, wholesomeness, food, eating
      environment and meal fellowship. When planning and realizing nursing actions
      concerning eating, the willingness to eat has to be observed. The desire within
      every individual has to be given consideration, including all factors as well as
      how they affect each other. The willingness to eat contains internal factors
      dependent on mood and personal values, as well as external factors dependent on
      wholesomeness, food, eating environment and meal fellowship. These factors
      contain qualitative dimensions, which affect elderly people's appetites as well
      as their quality of life to a varying extent. Through this, it can be seen that
      there is a connection between their desire or willingness to eat and their will
      to live.

PMID- 15147475
TI  - Meals in nursing homes.
AB  - Undernutrition is present among 33% of nursing home residents in Denmark. Hence,
      it is relevant to examine the meal situation at nursing homes to single out
      factors that may increase or reduce the residents' food intake. In the ongoing
      Danish nursing home debate it is claimed that a new type of nursing home improves
      the residents' meal situation with a positive effect on nutrition. The aim of
      this work is to test the general hypothesis that (i) residents appreciate the
      meal situation in these nursing homes and (ii) nutritional status of the
      residents is improved in this type of nursing home. This study was carried out in
      four Danish nursing homes at various locations in Denmark. The methods used are
      qualitative interviews and observations at four nursing homes in combination with
      measurement of body mass index (BMI) at two of the four nursing homes.
      Undernutrition is defined as a BMI below 20. The study could not confirm the
      general hypothesis, as a consistent improvement in the meal situation was not
      found in the nursing homes studied. But an indication of improved nutritional
      status was found in two of the nursing homes where the degree of undernutrition
      was lower than generally found in Denmark. Furthermore, the study indicated that
      the staff and the residents conceived the nursing homes differently.

PMID- 15147476
TI  - Ill health is powerlessness: a phenomenological study about worthlessness,
      limitations and suffering.
AB  - The aim of the study was to create an understanding of the different dimensions
      of subjective ill health through discovering the essence of ill health, based on
      the individual experience. A philosophical, phenomenological method has been
      employed, and in-depth interviews were conducted with 25 individuals. The
      findings showed that the essence of ill health is powerlessness, which is made by
      a self-image of worthlessness, a sense of being imprisoned in one's life
      situation, and emotional suffering. The individual views her/himself as
      worthless, based on societal norms, attitudes and human models. Incapability and
      a sense of worthlessness cause the individual to distrust her/himself and others.
      She/he is imprisoned in her/his own life situation due to limited choices and
      ability. Such a situation gives rise to apathy. Destructive feelings of
      alienation, anguish, shame and guilt take over, and the individual's autonomy and
      existence are threatened. Stigmatization results from suffering and a sense of
      worthlessness. The informants compensated for their vulnerability by means of
      human support, intimacy with others, a society adapted to disability, living in
      the present and awareness.

PMID- 15147477
TI  - A phenomenological hermeneutical method for researching lived experience.
AB  - This study describes a phenomenological hermeneutical method for interpreting
      interview texts inspired by the theory of interpretation presented by Paul
      Ricoeur. Narrative interviews are transcribed. A naive understanding of the text
      is formulated from an initial reading. The text is then divided into meaning
      units that are condensed and abstracted to form sub-themes, themes and possibly
      main themes, which are compared with the naive understanding for validation.
      Lastly the text is again read as a whole, the naive understanding and the themes
      are reflected on in relation to the literature about the meaning of lived
      experience and a comprehensive understanding is formulated. The comprehensive
      understanding discloses new possibilities for being in the world. This world can
      be described as the prefigured life world of the interviewees as configured in
      the interview and refigured first in the researcher's interpretation and second
      in the interpretation of the readers of the research report. This may help the
      readers refigure their own life.

PMID- 15147479
TI  - Women's experiences in connection with induced abortion - a feminist perspective.
AB  - Although abortions are common, few researchers have explored the experiences of
      women related to abortions. The aim of this qualitative study was to analyse
      women's experiences of induced abortion from a feminist perspective. Five women
      aged 19-33 years were interviewed about 1 month after their abortion. The
      interviews were analysed using thematic content analysis from which the following
      themes were identified: experiences connected with the decision-making process,
      experiences connected with the abortion and experiences after the abortion.
      Childhood experiences of divided families, financial problems, being too young,
      and an insecure partnership influenced the women's decision to have an abortion.
      Ambivalence about abortion was strongly expressed throughout the process. Despite
      positive attitudes towards abortion in general, the women had negative attitudes
      towards their own abortion. They described receiving most support from their
      mothers and friends, in the decision-making process, and least from their
      partners. After the abortion the women gained a feeling of maturity and
      experience although their ambivalence persisted. One conclusion drawn from our
      study is that nurses and midwives need to be aware of women's complex experiences
      with abortions in order to support and empower women who seek an abortion.

PMID- 15147478
TI  - Sense of coherence is a sensitive measure for changes in subjects with
      Parkinson's disease during 1 year.
AB  - To investigate subjective and objective changes in function in subjects with
      Parkinson's disease (PD) home visits with interviews were performed with a 1-year
      interval. Depressive symptoms were rated with the Geriatric Depression Scale,
      subjective health with the generic SF-36 scale and the disease-specific PDQ-8
      scale; objective changes were assessed according to the Hoehn and Yahr scale;
      insomnia was rated with an eight-item questionnaire and the sense of coherence
      (SOC) was determined with the short version of that scale. A total of 91 subjects
      (39 women and 52 men with a mean age of 70 years) living at home, most of them
      moderately to severely disabled, were interviewed. Time since diagnosis was <2
      years for 13%, 2-10 years for 55%, and >10 years for 32%. During the studied year
      the subjects' status declined significantly as shown by changes in both the PDQ-8
      and the Hoehn and Yahr scales. The most striking finding was a pronounced
      decrease in the SOC scale (p < 0.0001). This indicates that the subjects' ability
      to handle stress-related problems secondary to the progress of disease might have
      decreased. In order to optimize nursing care for subjects with PD, in addition to
      medical treatment, an assessment of the SOC could aid nursing staff in evaluating
      subjects' ability to handle their life situation.

PMID- 15147480
TI  - Older patients awaiting emergency department treatment.
AB  - The aim of this study was to describe, through observations and interviews with
      patients >/=75 years old and the relatives who accompanied them to the hospital,
      the conditions at the emergency department (ED) and the events that took place
      during the waiting period. Twenty older patients were studied, together with
      their relatives. A modification of a comparative design, the interpretative
      method 'grounded theory', was utilized. Open, nonparticipant observations were
      carried out; from the time patients were admitted until the time they were
      discharged. Patients were observed through all stages, for example, in the
      reception area, in the examination room, and in the X-ray department. The
      observations were supplemented with field notes and interviews with the older
      patients as they left the ED. The selective coding developed into six core
      variables that were the focus of the material. These were: unpleasant waiting,
      unnecessary waiting, lack of good routines during the waiting stage, suffering
      during the waiting stage, bad feelings during the waiting stage and nursing care
      during the waiting stage. The way, in which nursing care was carried out, which
      in this context is discussed in terms of praxis and poieses, appeared to be of
      major importance for the older peoples' experiences when visiting the ED.

PMID- 15147481
TI  - Factors associated with the attitudes and expectations of patients suffering from
      beta-thalassaemia: a cross-sectional study.
AB  - Regular transfusions and iron chelation therapy have transformed the life
      expectancy of homozygous beta-thalassaemia patients, so that it can now be
      considered a chronic condition. A health questionnaire survey of all adults
      suffering from beta-thalassaemia major receiving treatment on the Island of
      Crete, Greece was carried out with the aim of ascertaining the factors that are
      associated with their attitudes and expectations. The responses of 67 of the 72
      patients, aged 18-45 years, were analyzed using Principal Component Analysis to
      extract three component indicators (Adaptability, Optimism and Pessimism
      Indicators), which reflected their attitudes towards life and two component
      indicators (Healing and Therapy Indicators) that reflected their expectations
      from life. These were then tested against the respondents' socio-demographic
      characteristics, their health status and satisfaction with the services. It was
      found that the Optimism Indicator was associated with a positive comparative
      assessment of health status, while the Adaptability Indicator was associated with
      a positive subjective assessment of health status. The Adaptability Indicator was
      also higher in those satisfied with the services but it was lower in the best
      educated group. The pessimism indicator was associated with a negative
      comparative assessment of health status and with the lowest level education. The
      expectation indicators showed an interaction with gender and other parameters
      such as admission to hospital. The relationship between the attitudes and the
      expectations of patients suffering from a chronically disability condition and
      specific experiences during their treatment regimens raises several issues
      related to the need for better health education and psychological support of the
      group of patients, as well as issues related to the communication skills of the
      staff caring for them.

PMID- 15147482
TI  - What do men who are at risk of osteoporosis know about osteoporosis in developing
      countries? A pilot study in Isparta, Turkey.
AB  - The aim of this study was to investigate the knowledge, health beliefs and the
      knowledge sources of osteoporosis in Turkish males who are at risk of secondary
      causes of osteoporosis. One hundred and sixty men who had one of the systemic
      diseases or drugs which negatively affects bone metabolism were included in the
      study. Patients were asked to fill in a self-administered questionnaire which was
      modified from a validated questionnaire for Turkish female patients with
      osteoporosis. Twenty-two patients (15.7%) had never heard of a disease named
      osteoporosis. The mean score for general knowledge was 31.86 +/- 20.56 (over 100
      points). Only 20 (16.9%) patients had received information from a doctor. Seventy
      three (61.8%) of the patients stated that osteoporosis may be seen in men and
      only 42 (35.6%) patients were aware that they had a risk factor for osteoporosis.
      Most of the patients were unable to identify significant risk factors.
      Statistically significant positive correlation was found between KOS and
      patients' education levels (r = 0.453, p < 0.01). The findings in our study show
      that Turkish men who are at risk of osteoporosis do not have sufficient knowledge
      about osteoporosis and its consequences. We conclude that low education level of
      our patients accounts for poor osteoporosis knowledge.

PMID- 15147483
TI  - Reflecting on practice: are home visits prior to discharge worthwhile in
      geriatric inpatient care?
AB  - The discharge process of elderly clients from inpatient hospital care to their
      homes has lately received extensive attention but there is a lack of knowledge
      about the clients' problems as experienced in the home environment and their
      perceptions of corresponding home interventions prior to discharge. The aim of
      this clinical study therefore was to illuminate from both clients' and
      therapists' perspectives, common practice occupational therapy interventions at
      predischarge home visits in geriatric inpatient care. Home visits were carried
      out together with 23 clients before discharge during which their problems and the
      occupational therapy interventions at home were documented. After discharge, a
      follow-up home visit was carried out and the apprehensions of both parts
      regarding the interventions undertaken at the previous home visit were
      documented. In addition, a group interview was held with the nine therapists
      engaged in the study. The results exhibited a strong focus on physical
      disability, environmental issues and assistive devices. The clients were in
      general satisfied with the home visit interventions but their perceptions and
      responses to problems also differed from those of the therapists. When there was
      dissatisfaction, it resulted from serious delay in delivery of home modifications
      or devices, which posed a risk to their safety at home. For multiple reasons,
      both pre- and postdischarge home visits were found to be very important for the
      clients' safety.

PMID- 15147484
TI  - Psychiatric care staff's and care associates' perceptions of the concept of
      quality of care: a qualitative study.
AB  - Quality of care is a multidimensional concept and has been given different
      meanings in the literature. The aim in the present study was to describe how the
      psychiatric care staff and care associates perceived the concept of quality of
      care in the case of psychiatric care. Ten staff and 10 associates were
      interviewed. Qualitative method with a phenomenographic approach was used for the
      analysis. Four descriptive categories emerged: The patient's dignity is
      respected, The patient's participation in the care, The patient's recovery, and
      The patient's care environment plays an important role. Quality of care was
      perceived as a positive concept and as being of great importance for the
      patient's health and conditions of living. The results were of importance with
      regard to the forthcoming development of an instrument to measure the quality of
      psychiatric care.

PMID- 15147485
TI  - Reliability of the Body Awareness Scale-Health.
AB  - In physical therapy the clinical assessment Body Awareness Scale-Health (BAS-H)
      focusing on the quality of movements and movement behaviour has previously been
      studied for validity. The aim of this study was to address the inter-rater
      reliability and test-retest reliability in three groups. The groups assessed
      were: patients in psychiatric care with eating disorders (n = 26), patients in
      rehabilitation of prolonged musculoskeletal pain (n = 22) and healthy individuals
      (n = 22). Results revealed inter-rater reliability (n = 70) of the BAS-H total to
      be 79.9 % with acceptable agreement (accepting one scale-step of difference) and
      48.7% with perfect agreement. Weighted Kappa ranged between 0.34 and 0.92. Test
      retest reliability (n = 54) as a mean for both raters were found to be 90.5% for
      the BAS-H total with acceptable agreement and 60.4% with perfect agreement.
      Weighted Kappa ranged between 0.65 and 0.92. The BAS-H seems to be a reliable
      assessment in the rehabilitation of patient with prolonged pain, psychiatric
      disorders and healthy controls when used according to the manual. The authors,
      however, suggest some revisions.

PMID- 15147486
TI  - Registered Nurses' perceptions of geriatric rehabilitation nursing in three
      Scandinavian countries.
AB  - This study describes Registered Nurses' perceptions of geriatric rehabilitation
      nursing as well as their experiences of working in the rehabilitation of older
      patients in Denmark, Finland and Norway. The aim was to gain deeper insights into
      how Registered Nurses think about geriatric rehabilitation nursing and how their
      perceptions differ in these countries. The data were collected among 600
      Registered Nurses using a structured questionnaire with five background items and
      88 geriatric rehabilitation nursing items. The response rate was 65%. Data
      analysis was with SPSS statistical software. Geriatric rehabilitation nursing was
      experienced as something that required knowledge and experience, patience and
      creativity, as well as professional skills. The nurses talked with their patients
      about their rehabilitation goals, but not all nurses were aware of those goals.
      Progress in the rehabilitation process was evaluated on a daily basis and results
      were noted in the patients' records. The nurses motivated patients by giving them
      positive feedback, by preventing pain, by pausing to share with the patients
      their joy about progress, and by giving the patients the opportunity to cope with
      daily activities. The Registered Nurses in Denmark were more team oriented and
      they set out the goals in the patient's records more often than their colleagues
      did in Finland and Norway.

PMID- 15147487
TI  - Structuring the documentation of nursing care on the basis of a theoretical
      process model.
AB  - The aim of this study was to develop the documentation of the substance of
      nursing care on the basis of a theoretical caring process model. The theory is
      Eriksson's caring process model and her theory of health, suffering and caring.
      The approach of the research task was dialogue. As a research method Koski's
      adaptation of Gadamer's theory of hermeneutic experience was used, in which
      Gadamer's hermeneutic text interpretation is divided into four phases. The phases
      are the explicit analysis of preunderstanding, hermeneutic dialogue, the merging
      of horizons and active application. The dialogue is carried on between Eriksson's
      theory of health, suffering and caring and clinical nursing practice and between
      the caring process model and nursing practice. The goal is to achieve a new
      scientific view on which to base the documentation of nursing care. As a result
      of the dialogue a classification in accordance with Eriksson's caring-process
      model is presented. In the next phase of the study the classification is piloted
      in a clinical context. The purpose is to obtain knowledge of whether the
      suggested classification describes what, according to the theory, it should
      describe.

PMID- 15147488
TI  - Making a life worth living: neural correlates of well-being.
AB  - Despite the vast literature that has implicated asymmetric activation of the
      prefrontal cortex in approach-withdrawal motivation and emotion, no published
      reports have directly explored the neural correlates of well-being. Eighty-four
      right-handed adults (ages 57-60) completed self-report measures of eudaimonic
      well-being, hedonic well-being, and positive affect prior to resting
      electroencephalography. As hypothesized, greater left than right superior frontal
      activation was associated with higher levels of both forms of well-being.
      Hemisphere-specific analyses documented the importance of goal-directed approach
      tendencies beyond those captured by approach-related positive affect for
      eudaimonic but not for hedonic well-being. Appropriately engaging sources of
      appetitive motivation, characteristic of higher left than right baseline levels
      of prefrontal activation, may encourage the experience of well-being.

PMID- 15147490
TI  - Can a nonspecific bias toward top-heavy patterns explain newborns' face
      preference?
AB  - This study examined newborns' face preference using images of natural and
      scrambled faces in which the location of the inner features was distorted. The
      results demonstrate that newborns' face preference is not confined to schematic
      configurations, but can be obtained also with veridical faces. Moreover, this
      phenomenon is not produced by a specific bias toward the face geometry, but
      derives from a domain-general bias toward configurations with more elements in
      the upper than in the lower half (i.e., top-heavy patterns). These results
      suggest that it may be unnecessary to assume the existence of a prewired tendency
      to orient toward the face geometry, and support the idea that faces do not
      possess a special status in newborns' visual world.

PMID- 15147489
TI  - Scholastic Assessment or g? The relationship between the Scholastic Assessment
      Test and general cognitive ability.
AB  - There is little evidence showing the relationship between the Scholastic
      Assessment Test (SAT) and g (general intelligence). This research established the
      relationship between SAT and g, as well as the appropriateness of the SAT as a
      measure of g, and examined the SAT as a premorbid measure of intelligence. In
      Study 1, we used the National Longitudinal Survey of Youth 1979. Measures of g
      were extracted from the Armed Services Vocational Aptitude Battery and correlated
      with SAT scores of 917 participants. The resulting correlation was.82 (.86
      corrected for nonlinearity). Study 2 investigated the correlation between revised
      and recentered SAT scores and scores on the Raven's Advanced Progressive Matrices
      among 104 undergraduates. The resulting correlation was.483 (.72 corrected for
      restricted range). These studies indicate that the SAT is mainly a test of g. We
      provide equations for converting SAT scores to estimated IQs; such conversion
      could be useful for estimating premorbid IQ or conducting individual difference
      research with college students.

PMID- 15147491
TI  - When children ask, "What is it?" what do they want to know about artifacts?
AB  - When children ask, "What is it?" are they seeking information about what
      something is called or what kind of thing it is? To find out, we gave 2-, 3-, and
      4-year-olds (32 at each age) the opportunity to inquire about unfamiliar
      artifacts. An ambiguous question was answered with a name or with functional
      information, depending on the group to which the children were assigned. Children
      were inclined to follow up with additional questions about the object when they
      had been told its name, but seemed satisfied with the answer when they had been
      told the object's function. Moreover, children in the name condition tended to
      substitute questions about function for ambiguous questions over the course of
      the session. These results indicate that children are motivated to discover what
      kinds of things novel artifacts are, and that young children, like adults,
      conceive of artifact kinds in terms of their functions.

PMID- 15147492
TI  - Functional magnetic resonance imaging provides new constraints on theories of the
      psychological refractory period.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the
      psychological refractory period (PRP), the delay in the response to the second of
      two tasks occurring in immediate succession. Our results were consistent with
      prior work on the PRP in that when two visual-manual tasks were presented within
      100 ms of each other, the second response was delayed on the order of 500 ms,
      compared with when the two tasks were separated by 1,500 ms. Surprisingly, in
      brain regions postulated to be important for executive functions, there was
      virtually no increase in brain activation in the short-interval compared with the
      long-interval condition. These data suggest that passive queuing, rather than
      active monitoring, occurs during the PRP.

PMID- 15147493
TI  - Neural synergy between kinetic vision and touch.
AB  - Ambiguous visual information often produces unstable visual perception. In four
      psychophysical experiments, we found that unambiguous tactile information about
      the direction of rotation of a globe whose three-dimensional structure is
      ambiguous significantly influences visual perception of the globe. This
      disambiguation of vision by touch occurs only when the two modalities are
      stimulated concurrently, however. Using functional magnetic resonance imaging, we
      discovered that touching the rotating globe, even when not looking at it,
      reliably activates the middle temporal visual area (MT+), a brain region commonly
      thought to be crucially involved in registering structure from motion. Considered
      together, our results show that the brain draws on somatosensory information to
      resolve visual conflict.

PMID- 15147494
TI  - Use of cognitive versus perceptual heading during imagined locomotion depends on
      the response mode.
AB  - Three experiments investigated whether the systematic errors previously observed
      in a triangle-completion task were caused by failures to form and update a
      cognitive heading or by use of perceived heading (even though an updated
      cognitive heading was available) during the response. These errors were
      replicated when participants indicated the origin of triangular paths they had
      imagined walking by turning their bodies toward the origin, but not when they
      responded verbally. The results indicate that participants are capable of
      updating their cognitive heading using imagined movements and suggest that the
      systematic errors previously observed were a result of the strong attachment of
      responses such as turns to a perceptual representation of the physical body.

PMID- 15147495
TI  - Is syntax separate or shared between languages? Cross-linguistic syntactic
      priming in Spanish-English bilinguals.
AB  - Much research in bilingualism has addressed the question of the extent to which
      lexical information is shared between languages. The present study investigated
      whether syntactic information is shared by testing if syntactic priming occurs
      between languages. Spanish-English bilingual participants described cards to each
      other in a dialogue game. We found that a participant who had just heard a
      sentence in Spanish tended to use the same type of sentence when describing the
      next card in English. In particular, English passives were considerably more
      common following a Spanish passive than otherwise. We use the results to extend
      current models of the representation of grammatical information to bilinguals.

PMID- 15147496
TI  - Using pointing and describing to achieve joint focus of attention in dialogue.
AB  - Pointing was shown to focus attention in dialogue. Pairs of people talked and
      gestured to identify targets from arrays visible to both of them. Arrays were
      located at five distances: arm length (0 cm), 25 cm, 50 cm, 75 cm, and 100 cm.
      Some pairs could point; others could not. People relied more on pointing and less
      on language as distance decreased. Pointing especially suppressed descriptions of
      target location, suggesting that it was used to focus attention on a spatial
      region.

PMID- 15147497
TI  - Divide and conquer: how object files adapt when a persisting object splits into
      two.
AB  - Coherent visual experience requires not only segmenting incoming visual input
      into a structured scene of objects, but also binding discrete views of objects
      into dynamic representations that persist across time and motion. However,
      surprisingly little work has explored the principles that guide the construction
      and maintenance of such persisting object representations. What causes a part of
      the visual field to be treated as the same object over time? In the cognitive
      development literature, a key principle of object persistence is cohesion: An
      object must always maintain a single bounded contour. Here we demonstrate for the
      first time that mechanisms of adult midlevel vision are affected by cohesion
      violations. Using the object-file framework, we tested whether object-specific
      preview benefits-a hallmark of persisting object representations-are obtained for
      dynamic objects that split into two during their motion. We found that these
      preview benefits do not fully persist through such cohesion violations without
      incurring significant performance costs. These results illustrate how cohesion is
      employed as a constraint that guides the maintenance of object representations in
      adult midlevel vision.

PMID- 15147498
TI  - Does action make the link between number and space representation? Visuo-manual
      adaptation improves number bisection in unilateral neglect.
AB  - If the visual world is artificially shifted by only 10 degrees, people initially
      experience difficulty in directing their actions toward visual goals, but then
      rapidly compensate the visual distortion. The consequence of such adaptation can
      be measured as visual and proprioceptive aftereffects, as well as by performance
      on pointing tasks without visual feedback. Recent work has shown that more
      cognitive deficits can be improved following prism adaptation in patients with
      unilateral neglect. Here we show that a short visuo-manual adaptation to prisms
      improves performance on a mental number-bisection task recently shown to be
      impaired in unilateral neglect. The association previously found between space
      and number representation (the mental number line) may thus be grounded in common
      action principles. Our results suggest that visuo-motor plasticity functionally
      links parietal areas involved in space and number representation.

PMID- 15147499
TI  - Microsaccades keep the eyes' balance during fixation.
AB  - During fixation of a stationary target, small involuntary eye movements exhibit
      an erratic trajectory-a random walk. Two types of these fixational eye movements
      are drift and microsaccades (small-amplitude saccades). We investigated
      fixational eye movements and binocular coordination using a statistical analysis
      that had previously been applied to human posture control. This random-walk
      analysis uncovered two different time scales in fixational eye movements and
      identified specific functions for microsaccades. On a short time scale,
      microsaccades enhanced perception by increasing fixation errors. On a long time
      scale, microsaccades reduced fixation errors and binocular disparity (relative to
      pure drift movements). Thus, our findings clarify the role of oculomotor
      processes during fixation.

PMID- 15147500
TI  - Regulation and function of somatostatin receptors.
AB  - This review summarizes the latest advances that have been made to elucidate the
      somatostatinergic system in respect to somatostatin receptor evolution, the
      development of receptor agonists/antagonists, receptor regulation, signal
      transduction, effects on cell proliferation, receptor-receptor or receptor
      protein interactions and receptor function.

PMID- 15147501
TI  - Pro-regenerative properties of cytokine-activated astrocytes.
AB  - The prevailing view of the astrocytic response to injury is that reactive
      astrocytes impede the regenerative process by forming scar tissue. As the levels
      of many cytokines dramatically increase following CNS insult and as this increase
      in cytokine expression precedes the production of the glial scar, a long-standing
      view has been that cytokines diminish neuronal survival and regeneration by
      stimulating the formation of astrogliotic scar tissue. However, there is a wealth
      of data indicating that cytokines "activate" astrocytes, and that cytokine
      stimulated astrocytes can promote the recovery of CNS function. Supporting
      evidence demonstrates that cytokine-activated astrocytes produce energy
      substrates and trophic factors for neurons and oligodendrocytes, act as free
      radical and excess glutamate scavengers, actively restore the blood-brain
      barrier, promote neovascularization, restore CNS ionic homeostasis, promote
      remyelination and also stimulate neurogenesis from neural stem cells.
      Accordingly, a re-assessment of cytokine-activated astrocytes is necessary. Here,
      we review studies that promote the thesis that cytokines elicit potent
      neuroprotective and regenerative responses from astrocytes.

PMID- 15147502
TI  - Acute ammonia intoxication induces an NMDA receptor-mediated increase in poly(ADP
      ribose) polymerase level and NAD metabolism in nuclei of rat brain cells.
AB  - Acute ammonia toxicity is mediated by excessive activation of NMDA receptors.
      Activation of NMDA receptors leads to activation of poly(ADP-ribose) polymerase
      (PARP) which mediates NMDA excitotoxicity. PARP is activated following DNA damage
      and may lead to cell death via NAD+ and ATP depletion. The aim of the present
      work was to assess whether acute ammonia intoxication in vivo leads to increased
      PARP in brain cells nuclei and to altered NAD+ and superoxide metabolism and the
      contribution of NMDA receptors to these alterations. Acute ammonia intoxication
      increases PARP content twofold in brain cells nuclei.NAD+ content decreased by
      55% in rats injected with ammonia. This was not due to decreased NAD+ synthetase
      nor increased NAD+ hydrolase activities and would be due to increased NAD+
      consumption by PARP. Superoxide radical formation increased by 75% in nuclei of
      brains of rats injected with ammonia, that also induced protein nitrotyrosylation
      and DNA damage. Blocking NMDA receptors prevented ammonia-induced PARP,
      superoxide and nitrotyrosylation increase, DNA damage and NAD+ decrease. These
      results show that acute ammonia intoxication in vivo leads to activation of NMDA
      receptors, leading to increased superoxide formation and PARP content and
      depletion of NAD+ in brain cells nuclei that contribute to ammonia toxicity.

PMID- 15147503
TI  - Stress-induced activation of the immediate early gene Arc (activity-regulated
      cytoskeleton-associated protein) is restricted to telencephalic areas in the rat
      brain: relationship to c-fos mRNA.
AB  - Arc is an effector immediate early gene whose expression is induced in situations
      of increased neuronal activity. However, there is no report on the influence of
      stress on Arc expression. Here, we compared the induction of both c-fos and Arc
      mRNAs in the brain of rats exposed to one of three different stressful
      situations: novel environment, forced swimming and immobilization. An absent or
      weak c-fos mRNA signal was observed in control rats, whereas those exposed to one
      of three stressors showed enhanced c-fos expression in a wide range of brain
      areas. Constitutive Arc expression was observed in some areas such as cortex,
      striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex. In
      response to stressors, a strong induction of Arc was observed, but the pattern
      was different from that of c-fos. For instance, activation of Arc but not c-fos
      was observed in the nucleus accumbens after immobilization and in the hippocampus
      after novel environment. No Arc induction was observed in diencephalic and
      brainstem areas. The present data show that Arc has a neuroanatomically
      restricted pattern of induction in the brain after emotional stress.
      Telencephalic activation suggests that a more intense induction of synaptic
      plasticity is occurring in this area after exposure to emotional stressors.

PMID- 15147504
TI  - Regulation of protein kinase C by the anti-Parkinson drug, MAO-B inhibitor,
      rasagiline and its derivatives, in vivo.
AB  - We have recently shown that the anti-Parkinson-propargyl-containing monoamine
      oxidase B (MAO-B) inhibitor drug, rasagiline [N-propargyl-(1R)-aminoindan], and
      its cholinesterase inhibitor derivatives TV3326 and TV3279, regulate amyloid
      precursor protein (APP) processing by a protein kinase C (PKC)-dependent
      mechanism in SH-SY5Y neuroblastoma and PC12 cells. In the present study, we
      investigated the effect of rasagiline and its derivatives on the regulation of
      the PKC-dependent mechanism and APP processing under in vivo conditions.
      Administration of rasagiline (0.1 mg/kg) to male C57/BL mice for 14 days
      significantly decreased membrane-bound holoprotein APP levels in the hippocampus.
      Additionally, we observed that rasagiline up-regulated p-PKC levels and the
      expression of alpha and epsilon PKC isozymes in the hippocampus, indicating that
      the mechanism by which rasagiline affects APP processing may be related to PKC
      associated signalling. The results also demonstrate that rasagiline treatment
      significantly elevated the levels of phosphorylated myristoylated alanine-rich C
      kinase substrate (p-MARCKS), a major substrate for PKC, as well as the levels of
      receptors for activated C kinase 1 (RACK1). Similar effects on APP and PKC levels
      were also demonstrated for the two cholinesterase inhibitor derivatives of
      rasagiline, TV3326 and TV3279. These results indicate that rasagiline and its
      derivatives regulate PKC-dependent mechanisms and APP processing. The activation
      and induction of PKC and MARCKS by these drugs may have a crucial role not only
      in their neuroprotective activity, but also in their ability to affect neuronal
      plasticity and spatial learning processes.

PMID- 15147505
TI  - Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in
      substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double
      alpha/gamma-synuclein null mutant mice.
AB  - The growing body of evidence suggests that intermediate products of alpha
      synuclein aggregation cause death of sensitive populations of neurones,
      particularly dopaminergic neurones, which is a critical event in the development
      of Parkinson's disease and other synucleinopathies. The role of two other members
      of the family, beta-synuclein and gamma-synuclein, in neurodegeneration is less
      understood. We studied the effect of inactivation of gamma-synuclein gene on
      mouse midbrain dopaminergic neurones. Reduced number of dopaminergic neurones was
      found in substantia nigra pars compacta (SNpc) but not in ventral tegmental area
      (VTA) of early post-natal and adult gamma-synuclein null mutant mice. Similar
      reductions were revealed in alpha-synuclein and double alpha-synuclein/gamma
      synuclein null mutant animals. However, in none of these mutants did this lead to
      significant changes of striatal dopamine or dopamine metabolite levels and motor
      dysfunction. In all three studied types of null mutants, dopaminergic neurones of
      SNpc were resistant to methyl-phenyl-tetrahydropyridine (MPTP) toxicity. We
      propose that both synucleins are important for effective survival of SNpc
      neurones during critical period of development but, in the absence of these
      proteins, permanent activation of compensatory mechanisms allow many neurones to
      survive and become resistant to certain toxic insults.

PMID- 15147506
TI  - Mutations in the extracellular domains of glutamate-gated chloride channel alpha3
      and beta subunits from ivermectin-resistant Cooperia oncophora affect agonist
      sensitivity.
AB  - Two full-length glutamate-gated chloride channel (GluCl) cDNAs, encoding
      GluClalpha3 and GluClbeta subunits, were cloned from ivermectin-susceptible (IVS)
      and -resistant (IVR) Cooperia oncophora adult worms. The IVS and IVR GluClalpha3
      subunits differ at three amino acid positions, while the IVS and IVR GluClbeta
      subunits differ at two amino acid positions. The aim of this study was to
      determine whether mutations in the IVR subunits affect agonist sensitivity. The
      subunits were expressed singly and in combination in Xenopus laevis oocytes.
      Electrophysiological whole-cell voltage-clamp recordings showed that mutations in
      the IVR GluClalpha3 caused a modest but significant threefold loss of sensitivity
      to glutamate, the natural ligand for GluCl receptors. As well, a significant
      decrease in sensitivity to the anthelmintics ivermectin and moxidectin was
      observed in the IVR GluClalpha3 receptor. Mutations in the IVR GluClbeta subunit
      abolished glutamate sensitivity. Co-expressing the IVS GluClalpha3 and GluClbeta
      subunits resulted in heteromeric channels that were more sensitive to glutamate
      than the respective homomeric channels, demonstrating co-assembly of the
      subunits. In contrast, the heteromeric IVR channels were less sensitive to
      glutamate than the homomeric IVR GluClalpha3 channels. The heteromeric IVS
      channels were significantly more sensitive to glutamate than the heteromeric IVR
      channels. Of the three amino acids distinguishing the IVS and IVR GluClalpha3
      subunits, only one of them, L256F, accounted for the differences in response
      between the IVS and IVR GluClalpha3 homomeric channels.

PMID- 15147507
TI  - Hypoxia induces adenosine release from the rat carotid body.
AB  - The effect of hypoxia on the release of adenosine was studied in vitro in the rat
      whole carotid body (CB) and compared with the effect of hypoxia (2%, 5% and 10%
      O(2)) on adenosine concentrations in superior cervical ganglia (SCG) and carotid
      arteries. Moderate hypoxia (10% O(2)) increased adenosine concentrations released
      from the CBs by 44%, but was not a strong enough stimulus to evoke adenosine
      release from SCG and arterial tissue. The extracellular pathways of adenosine
      production in rat CBs in normoxia and hypoxia were also investigated. S-(p
      nitrobenzyl)-6-thioinosine (NBTI) and dipyridamole were used as pharmacological
      tools to inhibit adenosine equilibrative transporters (ENT) and alpha,beta
      methylene ADP (AOPCP) to inhibit ecto-5'-nucleotidase. Approximately 40% of
      extracellular adenosine in the CB came from the extracellular catabolism of ATP,
      under both normoxic and hypoxic conditions. Low pO(2) triggers adenosine efflux
      through activation of NBTI-sensitive ENT. This effect was only apparent in
      hypoxia and when adenosine extracellular concentrations were reduced by the
      blockade of ecto-5'-nucleotidase. We concluded that CB chemoreceptor sensitivity
      could be related to its low threshold for the release of adenosine in response to
      hypoxia here quantified for the first time.

PMID- 15147508
TI  - In vivo exposure to carbon monoxide causes delayed impairment of activation of
      soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum.
AB  - Carbon monoxide induces delayed neurological and neuropathological alterations,
      including memory loss and cognitive impairment. The bases for the delay remain
      unknown. Activation of soluble guanylate cyclase by nitric oxide modulates some
      forms of learning and memory. Carbon monoxide binds to soluble guanylate cyclase,
      activating it but interfering with its activation by nitric oxide. The aim of
      this work was to assess whether exposure of rats to carbon monoxide alters the
      activity of soluble guanylate cyclase or its modulation by nitric oxide in
      cerebellum or cerebral cortex. Rats exposed chronically or acutely to carbon
      monoxide were killed 24 h or 7 days later. Acute carbon monoxide exposure
      decreased cyclic guanosine monophosphate (cGMP) content and reduced activation of
      soluble guanylate cyclase by nitric oxide. Cortex was more sensitive than
      cerebellum to chronic exposure, which reduced activation of soluble guanylate
      cyclase by nitric oxide in cortex. In cerebellum, chronic exposure induced
      delayed impairment of soluble guanylate cyclase activation by nitric oxide. Acute
      exposure effects were also stronger at 7 days than at 24 h after exposure. This
      delayed impaired modulation of soluble guanylate cyclase by nitric oxide may
      contribute to delayed memory loss and cognitive impairment in humans exposed to
      carbon monoxide.

PMID- 15147510
TI  - Multiple sites of ethanol action in alpha1 and alpha2 glycine receptors suggested
      by sensitivity to pressure antagonism.
AB  - The current study used an ethanol antagonist, increased atmospheric pressure, to
      test the hypothesis that ethanol acts on multiple sites in glycine receptors
      (GlyRs). The effects of 12 times normal atmospheric pressure of helium-oxygen gas
      (pressure) on ethanol-induced potentiation of GlyR function in Xenopus oocytes
      expressing human alpha1, alpha2 or the mutant alpha1(A52S) GlyRs were measured
      using two-electrode voltage clamp. Pressure reversibly antagonized potentiation
      of glycine in alpha1 GlyR by 40-200 mm ethanol, but did not antagonize 10 and 25
      mm ethanol in the same oocytes. In contrast, pressure did not significantly
      affect potentiation of glycine by 25-100 mm ethanol in alpha2 GlyRs, nor did
      pressure alter ethanol response in the A52S mutant. Pressure did not affect
      baseline receptor function or response to glycine in the absence of ethanol.
      These findings provide the first direct evidence for multiple sites of ethanol
      action in GlyRs. The sites can be differentiated on the basis of ethanol
      concentration, subunit and structural composition and sensitivities to pressure
      antagonism of ethanol. Parallel studies with butanol support this conclusion. The
      mutant alpha1(A52S) GlyR findings suggest that increased attention should be
      focused on the amino terminus as a potential target for ethanol action.

PMID- 15147509
TI  - Neisseria meningitidis-induced death of cerebrovascular endothelium: mechanisms
      triggering transcriptional activation of inducible nitric oxide synthase.
AB  - The intense host response to meningococcus reflects marked functional and
      morphological alterations in blood-brain barriers. We showed previously that
      mouse-derived cerebrovascular endothelium responded to meningococcal lysates with
      a robust nitric oxide (NO) response, resulting in the loss of cell viability. To
      understand how the NO synthase-2 gene in endothelium is activated by
      meningococcus, we investigated upstream roles for specific protein kinases. Using
      known kinase inhibitors, and measuring both mRNA expression and nitrite release,
      we found MAPK/ERK kinase (MEK)2, p38 kinase and phosphoinositide 3-kinase (but
      not MEK1 or phospholipase C) to be implicated in the NO synthase-2 response.
      Recruitment of these kinases by meningococcus did not depend on the prior release
      of the proinflammatory cytokines tumour necrosis factor alpha or interleukin
      1beta from endothelium. These endothelial cells were found to express toll-like
      receptors (TLR) 2, 4 and 9 and antibodies directed against TLR 2 and 4 (but not
      TLR 9) blocked the NO synthase-2 response to meningococcus. Both meningococcus
      induced translocation of nuclear factor-kB (NF-kB) and endothelial cell death
      were blocked by a known inhibitor of p38 kinase. Calpain inhibitor-1 blocked the
      NO synthase-2 response to meningococcus, which is further evidence of a role for
      NF-kB.

PMID- 15147511
TI  - TorsinB--perinuclear location and association with torsinA.
AB  - The torsins comprise a four-member family of AAA+ chaperone proteins, including
      torsinA, torsinB, torp2A and torp3A in humans. Mutations in torsinA underlie
      early onset torsion dystonia, an autosomal dominant, neurologically based
      movement disorder. TorsinB is highly homologous to torsinA with its gene adjacent
      to that for torsinA on human chromosome 9q34. Antibodies have been generated
      which can distinguish torsinA and torsinB from each other, and from the torps in
      human and rodent cells. TorsinB (approximately MW 38 kDa), like torsinA (
      approximately MW 37 kDa), is an N-glycosylated protein and both reside primarily
      in the endoplasmic reticulum (ER) and nuclear envelope in cultured cells.
      Immunoprecipitation studies in cultured cells and human brain tissue indicate
      that torsinA and torsinB are associated with each other in cells. Overexpression
      of both wild-type torsinB and mutant torsinA lead to enrichment of the protein in
      the nuclear envelope and formation of large cytoplasmic inclusions. We conclude
      that torsinB and torsinA are localized in overlapping cell compartments within
      the same protein complex, and thus may carry out related functions in vivo.

PMID- 15147512
TI  - Taurine-induced long-lasting potentiation in the rat hippocampus shows a partial
      dissociation from total hippocampal taurine content and independence from
      activation of known taurine transporters.
AB  - Perfusion with high millimolar levels of taurine evoked a long-lasting
      potentiation (LLP-TAU) of synaptic transmission in the Schaffer-collateral CA1
      region of the rat hippocampus. Although LLP-TAU showed some correlations to
      increases in the total taurine content of hippocampal slices, it could not be
      blocked by the taurine transport inhibitor guanidinoethanesulfonic acid (GES),
      which was able to significantly reduce total slice taurine uptake. Inhibition of
      GABA transport by either nipecotic acid or beta-guanidinopropionate failed to
      abolish LLP-TAU and had no significant effect on taurine uptake. The combination
      of GES and nipecotic acid also had no significant effect on LLP-TAU. Experiments
      with transportable structural analogs of taurine (beta-aminoisobutyric acid,
      homotaurine, and isethionic acid) suggest that activation of classical taurine
      transport pathways does not always yield a robust LLP-TAU. Hippocampal LLP-TAU
      could be significantly attenuated, however, by pre-incubation with submillimolar
      levels of taurine. In summary, the development of LLP-TAU in the rat hippocampus
      appears to be associated with the intracellular accumulation rather than the
      activation of known transporters of taurine, but the precise means of its
      accumulation remains to be identified.

PMID- 15147513
TI  - 3-Nitropropionic acid-induced neurotoxicity--assessed by ultra high resolution
      positron emission tomography with comparison to magnetic resonance spectroscopy.
AB  - To explore acute and long-term effects of 3-nitropropionic acid (3-NP)-induced
      neurotoxicity, longitudinal positron emission tomography (PET) studies of energy
      metabolism and magnetic resonance spectroscopic (MRS) studies of neurochemicals
      were conducted in a rat model. The first injection of 3-NP (20 mg/kg i.p.) was
      followed by MRS study of neurochemicals and PET study of glucose utilization
      using [(18)F]2-fluorodeoxy-D-glucose ((18)F-FDG). After that, 3-NP administration
      was done two times a day with a dose of 10 mg/kg i.p. until animals were
      symptomatic or for a maximum of 5 days combined with daily PET studies. Long-term
      effects were investigated 4 weeks and 4 months after cessation of 3-NP. These
      studies showed a significant inter-animal variation in response of 3-NP toxicity.
      Animals that developed large striatal lesions had decreased glucose utilization
      in the striatum and cortex 1 day after starting 3-NP injections. Similarly
      succinate and lactate/macromolecule levels were enhanced; these changes being,
      however, reversible. Progressive degeneration was observed by decreasing striatal
      glucose utilization and N-acetylaspartate (NAA) and increasing choline. These
      observations paralleled with weight loss and deficits in behavior. Animals that
      did not develop lesions showed reversible enhancement in cortical glucose
      utilization and no change in striatal glucose utilization or neurochemicals or
      locomotor activity.

PMID- 15147514
TI  - Enhanced G-protein activation by a mixture of Abeta(25-35), Abeta(1-40/42) and
      zinc.
AB  - Beta-amyloid peptides (Abetas) bind to several G-protein coupled receptor
      proteins and stimulate GTPase activity in neurons. In this study we determined
      the effects of Abeta(1-42), Abeta(1-40), Abeta(25-35) and their mixtures on
      [(35)S]GTP binding in rat brain cortical membranes in the absence and presence of
      zinc. We found that the Abetas alone induced a concentration-dependent activation
      of G-proteins (IC50 approximately 10(-6) m), while aggregated Abeta fibrils only
      affected GTP binding at concentrations above 10(-5) m. Mixing Abeta(25-35) with
      Abeta(1-42) or Abeta(1-40) induced a several-fold increase in GTP-binding. This
      potentiation followed a bell shaped curve with a maximum at 50 : 50 ratios. No
      potentiating effect could be seen by mixing Abeta(1-40) and Abeta(1-42) or highly
      aggregated Abetas. Zinc had no effect on Abeta(1-40/42) but strongly potentiated
      the Abeta(25-35) or the mixed peptides-induced GTP-binding. Changes in secondary
      structure accompanied the mixed peptides or the peptide/zinc complexes induced
      potentiation, revealing that structural alterations are behind the increased
      biological action. These concentration dependent potentiating effects of zinc and
      the peptide mixtures could be physiologically important at brain regions where
      peptide fragments and/or zinc are present at elevated concentrations.

PMID- 15147515
TI  - Regulation of glycogen synthase kinase-3beta by products of lipid peroxidation in
      human neuroblastoma cells.
AB  - The potential role of 4-hydroxynonenal (HNE), a major product of membrane lipid
      peroxidation, in regulating glycogen synthase kinase-3beta (GSK3beta) activity
      was examined in human neuroblastoma IMR-32 cells. The inhibition of GSK3beta
      activity by HNE was observed by in vitro kinase assays with two substrates, the
      synthetic glycogen synthase peptide-2 and the human recombinant tau. GSK3beta
      activity is regulated by Ser9 (inhibitory) and Tyr216 (stimulatory)
      phosphorylation. By using specific activity-dependent phospho-antibodies,
      immunoblot analysis revealed that HNE induces an increase in phosphorylation of
      GSK3beta in Ser9, enhancing basal phosphatidylinositol 3-kinase (PI3K)/AKT and
      extracellular signal-regulated kinase 2 (ERK2) signalling pathways. Ser9-GSK3beta
      phosphorylation induced by HNE was abolished by treatment with LY294002 or U0126,
      two inhibitors of PI3K/AKT and ERK pathways, respectively. These experiments
      provide evidence for a crucial role of the PI3K/AKT and ERK2 pathways as
      intracellular targets of HNE that mediate the inhibition of GSK3beta activity in
      regulating cellular response to HNE in viable cells under conditions in which
      membrane lipid peroxidation occurs. These data support a key role for GSK3beta as
      a mediator of the signalling pathways activated by oxidative stress, and
      therefore it may be included among the redox-sensitive enzymes.

PMID- 15147516
TI  - Neuroprotective properties of Bcl-w in Alzheimer disease.
AB  - While there is a host of pro-apoptotic stimuli that target neurons in Alzheimer
      disease (AD), given the chronicity of the disease and the survival of many
      neurons, those neurons must either avoid or, at minimum, delay apoptotic death
      signaling. In this study, we investigated Bcl-w, a novel member of the Bcl-2
      family that promotes cell survival. In AD, we found increased levels of Bcl-w
      associated with neurofibrillary pathology and punctate intracytoplasmic
      structures whereas, in marked contrast, there are only low diffuse levels of Bcl
      w in the neuronal cytoplasm of age-matched control cases. Immunoblot analysis
      confirmed that Bcl-w levels were significantly increased in AD. By electron
      microscopy, we determined that the increased Bcl-w expression in AD was
      ultrastructurally localized to mitochondria and neurofibrillary pathology. To
      investigate the cause and consequence of Bcl-w up-regulation in neurons, we found
      that fibrillized amyloid-beta led to increased Bcl-w protein levels in M17 human
      neuroblastoma cells, and that overexpression of Bcl-w significantly protected
      neurons against staurosporine- and amyloid-beta-induced apoptosis. Taken
      together, these series of results suggest that Bcl-w may play an important
      protective role in neurons in the diseased brain and that this aspect could be
      therapeutically harnessed to afford neuroprotection.

PMID- 15147517
TI  - A low molecular weight copper chelator crosses the blood-brain barrier and
      attenuates experimental autoimmune encephalomyelitis.
AB  - Increasing evidence suggests that enhanced production of reactive oxygen species
      (ROS) activates the MAP kinases, c-Jun N-terminal protein kinase (JNK) and
      mitogen-activated protein kinase MAPK (p38). These phosphorylated intermediates
      at the stress-activated pathway induce expression of matrix metalloproteinases
      (MMPs), leading to inflammatory responses and pathological damages involved in
      the etiology of multiple sclerosis (MS). Here we report that N-acetylcysteine
      amide (AD4) crosses the blood-brain barrier (BBB), chelates Cu(2+), which
      catalyzes free radical formation, and prevents ROS-induced activation of JNK, p38
      and MMP-9. In the myelin oligodendrocyte glycoprotein (MOG)-induced experimental
      autoimmune encephalomyelitis (EAE), a mouse model of MS, oral administration of
      AD4 drastically reduced the clinical signs, inflammation, MMP-9 activity, and
      protected axons from demylination damages. In agreement with the in vitro
      studies, we propose that ROS scavenging by AD4 in MOG-treated animals prevented
      MMP's induction and subsequent damages through inhibition of MAPK pathway. The
      low toxicity of AD4 coupled with BBB penetration makes this compound an excellent
      potential candidate for the therapy of MS and other neurodegenerative disorders.

PMID- 15147519
TI  - S100A1 codistributes with synapsin I in discrete brain areas and inhibits the F
      actin-bundling activity of synapsin I.
AB  - The Ca2+-sensor protein S100A1 was recently shown to bind in vitro to synapsins,
      a family of synaptic vesicle phosphoproteins involved in the regulation of
      neurotransmitter release. In this paper, we analyzed the distribution of S100A1
      and synapsin I in the CNS and investigated the effects of the S100A1/synapsin
      binding on the synapsin functional properties. Subcellular fractionation of rat
      brain homogenate revealed that S100A1 is present in the soluble fraction of
      isolated nerve endings. Confocal laser scanning microscopy and immunogold
      immunocytochemistry demonstrated that S100A1 and synapsin codistribute in a
      subpopulation (5-20%) of nerve terminals in the mouse cerebral and cerebellar
      cortices. By forming heterocomplexes with either dephosphorylated or
      phosphorylated synapsin I, S100A1 caused a dose- and Ca2+-dependent inhibition of
      synapsin-induced F-actin bundling and abolished synapsin dimerization, without
      affecting the binding of synapsin to F-actin, G-actin or synaptic vesicles. These
      data indicate that: (i) synapsins and S100A1 can interact in the nerve terminals
      where they are coexpresssed; (ii) S100A1 is unable to bind to SV-associated
      synapsin I and may function as a cytoplasmic store of monomeric synapsin I; and
      (iii) synapsin dimerization and interaction with S100A1 are mutually exclusive,
      suggesting an involvement of S100A1 in the Ca2+-dependent regulation of synaptic
      vesicle trafficking.

PMID- 15147521
TI  - Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role
      of UCP2 as a regulator of mitochondrial glutathione levels.
AB  - Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen
      species production in mitochondria. We performed a detailed study of brain
      injury, including regional and cellular distribution of UCP2 mRNA, as well as
      measures of oxidative stress markers following permanent middle cerebral artery
      occlusion in UCP2 knockout (KO) and wild-type (WT) mice. Three days post
      ischemia, there was a massive induction of UCP2 mRNA confined to microglia in the
      peri-infarct area of WT mice. KO mice were less sensitive to ischemia as assessed
      by reduced brain infarct size, decreased densities of deoxyuridine triphosphate
      nick end-labelling (TUNEL)-labelled cells in the peri-infact area and lower
      levels of lipid peroxidation compared with WT mice. This resistance may be
      related to the substantial increase of basal manganese superoxide dismutase
      levels in neurons of KO mice. Importantly, we found a specific decrease of
      mitochondrial glutathione (GSH) levels in UCP2 expressing microglia of WT, but
      not in KO mice after ischemia. This specific association between UCP2 and
      mitochondrial GSH levels regulation was further confirmed using
      lipopolysaccharide models of peripheral inflammation, and in purified peritoneal
      macrophages. Moreover, our data imply that UCP2 is not directly involved in the
      regulation of ROS production but acts by regulating mitochondrial GSH levels in
      microglia.

PMID- 15147518
TI  - Choline availability modulates human neuroblastoma cell proliferation and alters
      the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3
      gene.
AB  - Choline is an important methyl donor and a component of membrane phospholipids.
      In this study, we tested the hypothesis that choline availability can modulate
      cell proliferation and the methylation of genes that regulate cell cycling. In
      several other model systems, hypomethylation of cytosine bases that are followed
      by a guanosine (CpG) sites in the promoter region of a gene is associated with
      increased gene expression. We found that in choline-deficient IMR-32
      neuroblastoma cells, the promoter of the cyclin-dependent kinase inhibitor 3 gene
      (CDKN3) was hypomethylated. This change was associated with increased expression
      of CDKN3 and increased levels of its gene product, kinase-associated phosphatase
      (KAP), which inhibits the G(1)/S transition of the cell cycle by
      dephosphorylating cyclin-dependent kinases. Choline deficiency also reduced
      global DNA methylation. The percentage of cells that accumulated
      bromodeoxyuridine (proportional to cell proliferation) was 1.8 times lower in the
      choline-deficient cells than in the control cells. Phosphorylated retinoblastoma
      (p110) levels were 3 times lower in the choline-deficient cells than in control
      cells. These findings suggest that the mechanism whereby choline deficiency
      inhibits cell proliferation involves hypomethylation of key genes regulating cell
      cycling. This may be a mechanism for our previously reported observation that
      stem cell proliferation in hippocampus neuroepithelium is decreased in choline
      deficient rat and mouse fetuses.

PMID- 15147520
TI  - Delayed genomic responses to transient middle cerebral artery occlusion in the
      rat.
AB  - Ischemic stress in the brain induces acute and massive neuronal death in the
      targeted area, which is followed by a second round of detrimental processes,
      called delayed neuronal death, in the neighboring areas. To test the hypothesis
      that transcriptional control plays a role in the pathophysiology of the
      postischemic brain, the genomic responses that occurred in the brain at 3, 6 and,
      12 h, and 1, 2 or 4 days after transient middle cerebral artery occlusion (MCAO)
      were examined using a microarray harboring 5000 rat cDNAs. This analysis
      indicated that the number of up-regulated genes was gradually increased, along
      with the concomitant reduction in the number of down-regulated genes, until 12 h
      to 1 day after MCAO. It was followed by a delayed surge of down-regulated genes
      at 2 days after MCAO. Northern blots and immunohistological analysis confirmed
      the validity of these microarray data. We present a list of 85 genes that were up
      regulated more than 2.3-fold between 12 h and 4 days after MCAO, which included
      56 novel genes whose expression has not previously been implicated in ischemic
      pathophysiology. The list included genes involved in oxidative stress,
      inflammation, extracellular matrix (ECM), neuronal development and
      differentiation processes. Together these results suggest that the
      pathophysiology of the postischemic brain proceeds by the transcriptional
      activation of genes related to the process of delayed neuronal damage and/or
      recovery and repair.

PMID- 15147523
TI  - Increased expression of tissue-type transglutaminase following middle cerebral
      artery occlusion in rats.
AB  - Tissue-type transglutaminase (TG-2) has been implicated in neurodegenerative
      diseases. In this study, induction of TG-2 was studied in rats following
      transient middle cerebral artery occlusion. Alterations in 2,3,5
      triphenylterazolium chloride staining revealed maximum infarction 3 days after
      injury. Measurement of mRNA transcript levels by real-time PCR analysis showed
      both forms of TG-2 mRNA peaking on day 5 after injury in ipsilateral cortex, with
      greater induction of the full-length TG-2 (TG-L) transcript than the truncated
      form of the TG-2 (TG-S) transcript. However, in the ipsilateral hippocampus, peak
      induction of both forms of TG-2 mRNA peaked 1 day after injury and to a lesser
      extent than observed in the ipsilateral cortex. Western blot analysis
      demonstrated that TG-L protein expression progressively increased from 1 to 7
      days after ischemia, with greater expression in cortex than hippocampus (525 +/-
      10% vs. 196 +/- 8% of control, respectively). However, expression of TG-S was not
      detected. These results demonstrate that increased TG-2 mRNA and protein
      expression occurs in a delayed fashion following ischemic injury. The temporal
      profile of TG-2 induction after ischemia was similar to that observed after
      traumatic brain injury (previously described), suggesting a similar role of TG-2
      in both pathological conditions.

PMID- 15147522
TI  - Enhanced anandamide degradation is associated with neuronal apoptosis induced by
      the HIV-1 coat glycoprotein gp120 in the rat neocortex.
AB  - Human immunodeficiency virus type-1 coat glycoprotein gp120 causes delayed
      apoptosis in rat brain neocortex. Here, we investigated the possible role of the
      endocannabinoid system in this process. It is shown that gp120 causes a time
      dependent increase in the activity and immunoreactivity of the anandamide (AEA)
      hydrolyzing enzyme fatty acid amide hydrolase (FAAH), paralleled by increased
      activity of the AEA membrane transporter and decreased endogenous levels of AEA.
      The AEA-synthesizing phospholipase D and the AEA-binding receptors were not
      affected by gp120. None of the changes induced by gp120 in the cortex were
      induced by bovine serum albumin, nor were they observed in the hippocampus of the
      same animals. Also, the activity of 5-lipoxygenase, which generates AEA
      derivatives able to inhibit FAAH, decreased down to approximately 25% of the
      control activity upon gp120 treatment, due to reduced protein level (
      approximately 45%). In addition, the FAAH inhibitor methyl-arachidonoyl
      fluorophosphonate significantly reduced gp120-induced apoptosis in rat brain
      neocortex, whereas selective blockers of AEA membrane transporter or of AEA
      binding receptors were ineffective. Taken together, these results suggest that
      gp120, by activating FAAH, decreases endogenous levels of AEA, and the latter
      effect seems instrumental in the execution of delayed neuronal apoptosis in the
      brain neocortex of rats.

PMID- 15147525
TI  - Prevention of postmenopausal osteoporosis with pharmacological therapy: practice
      and possibilities.
AB  - Postmenopausal osteoporosis (PMO) is a common disease that will become more
      prevalent in the future, with costly implications for public health. Prevention
      of the disease and its consequences, namely fractures, is therefore, important
      for both the individual and society. This review discusses: the goals of PMO
      prevention; the identification of women at risk, including the use of bone
      mineral density and bone turnover markers; the relevance in the prevention
      setting of various current guidelines for PMO management; recent data on
      therapeutic options for the treatment and prevention of PMO, in particular
      bisphosphonates, hormone replacement therapy and several other new
      pharmacological agents. It concludes that it is crucial for PMO prevention to
      start before disease onset and that, in the light of recent evidence, the
      existing guidelines need updating if they are to continue to be relevant.

PMID- 15147524
TI  - Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice.
AB  - A growing body of evidence suggests a relationship between oxidative stress and
      beta-amyloid (Abeta) peptide accumulation, a hallmark in the pathogenesis of
      Alzheimer's disease (AD). However, a direct causal relationship between oxidative
      stress and Abeta pathology has not been established in vivo. Therefore, we
      crossed mice with a knockout of one allele of manganese superoxide dismutase
      (MnSOD), a critical antioxidant enzyme, with Tg19959 mice, which overexpress a
      doubly mutated human beta-amyloid precursor protein (APP). Partial deficiency of
      MnSOD, which is well established to cause elevated oxidative stress,
      significantly increased brain Abeta levels and Abeta plaque burden in Tg19959
      mice. These results indicate that oxidative stress can promote the pathogenesis
      of AD and further support the feasibility of antioxidant approaches for AD
      therapy.

PMID- 15147526
TI  - The expanding clinical spectrum of Anderson-Fabry disease: a challenge to
      diagnosis in the novel era of enzyme replacement therapy.
AB  - Anderson-Fabry disease is an X-linked recessive lysosomal storage disease
      resulting from deficient alpha-galactosidase A activity. The conception of the
      disease has changed within the last decade. Studies of the last years have shown
      that the disease is not limited to the classical full-blown manifestation in
      affected males, which is well known since more than a century, but may also occur
      in carrier females. The phenomenology may differ in severity and kind of organ
      manifestation. Cardiac and renal variants with solely disease manifestation of
      these organs have also been described in an increasing number. It is likely that
      a spectrum exists regarding alpha-galactosidase A activity in both genders on the
      one hand, and an additional one regarding the severity and the number of organs
      affected on the other. The purpose of this review is to sharpen physicians'
      perception of this disease. Early and accurate diagnosis is mandatory considering
      that this disorder is now, after introduction of the novel enzyme replacement
      therapy, a treatable disease.

PMID- 15147527
TI  - The platelet polymorphism PlA2 is a genetic risk factor for myocardial
      infarction.
AB  - OBJECTIVES: Platelet glycoprotein (GP) receptor IIb/IIIa plays a key role in the
      development of myocardial infarction (MI), and Pl(A2) is a polymorphism in the
      gene encoding this receptor. The prevalence of Pl(A2) shows pronounced
      geographical variation and has to our knowledge not been presented for a
      Scandinavian population before. Platelets from Pl(A2)-positive individuals show
      increased aggregability compared with platelets from Pl(A2)-negative individuals,
      and Pl(A2) genotypes might be associated with MI. The purpose of this study was
      to investigate the relation between the Pl(A2) polymorphism and MI in a large
      Scandinavian population. DESIGN: Case-control study. We included patients with
      angiographically verified CAD with and without previous MI and a group of healthy
      individuals matched for age, race, and sex. RESULTS: We studied the frequency of
      Pl(A2) in 1191 healthy individuals and 1019 patients with coronary artery disease
      (CAD). Amongst these patients, 529 subjects had suffered an MI previously. Pl(A2)
      was present in 28% of healthy individuals, 28% of patients with CAD but no MI,
      and in 35% of patients with CAD and MI. The difference between healthy
      individuals and MI patients was significant (P = 0.002). Furthermore, a graded
      relationship between the number of Pl(A2) alleles and the risk of MI was seen (P
      = 0.011). Associations between Pl(A2) and traditional cardiovascular risk factors
      as well as mean platelet volume were investigated. We found a significant
      interaction between Pl(A2) and serum cholesterol. CONCLUSION: In our Scandinavian
      study population the common platelet polymorphism Pl(A2) is significantly
      associated with an increased risk of MI, but not of CAD. Clinically, typing for
      Pl(A2) might have implications for antiplatelet therapy of patients with MI.

PMID- 15147528
TI  - Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men
      and women.
AB  - OBJECTIVES: The association between coffee consumption, type 2 diabetes and
      impaired glucose tolerance was examined. In addition, indicators of insulin
      sensitivity and beta-cell function according to homeostasis model assessment were
      studied in relation to coffee consumption. DESIGN: Population-based cross
      sectional study. SETTING AND SUBJECTS: The study comprised 7949 healthy Swedish
      subjects aged 35-56 years residing within five municipalities of Stockholm. An
      oral glucose tolerance test identified 55 men and 52 women with previously
      undiagnosed type 2 diabetes and 172 men and 167 women with impaired glucose
      tolerance. Information about coffee consumption and other factors was obtained by
      questionnaire. RESULTS: The relative risks (adjusted for potential confounders)
      of type 2 diabetes and impaired glucose tolerance when drinking >/=5 cups of
      coffee per day compared with </=2 cups per day in men were 0.45 [95% confidence
      intervals (CI) 0.22-0.92] and 0.63 (CI: 0.41-0.97), respectively, and in women
      0.27 (CI: 0.11-0.66) and 0.47 (CI: 0.29-0.76) respectively. In subjects with type
      2 diabetes and impaired glucose tolerance, high coffee consumption (>/=5 cups
      day(-1)) was inversely associated with insulin resistance. In addition, in those
      with type 2 diabetes and in women (not in men) with impaired glucose tolerance
      high coffee consumption was inversely associated with low beta-cell function. In
      women, but not obviously in men, with normal glucose tolerance, coffee
      consumption was associated with a reduced risk of insulin resistance.
      CONCLUSIONS: The results of this study indicated that high consumers of coffee
      have a reduced risk of type 2 diabetes and impaired glucose tolerance. The
      beneficial effects may involve both improved insulin sensitivity and enhanced
      insulin response.

PMID- 15147529
TI  - Readmissions and adverse drug reactions in internal medicine: the economic
      impact.
AB  - BACKGROUND: Recent studies show that nearly half of the hospitalized patients are
      readmitted within 6 months from discharge. No data exist about the relationship
      between adverse drug reactions (ADRs) and readmittance to a department of
      internal medicine. OBJECTIVES: The primary aims of the study were to determine if
      ADRs could be used as predictors for recurrent hospitalizations in internal
      medicine and to evaluate the economic impact of ADRs on hospitalization costs.
      DESIGN AND SETTING: A cohort-based, prospective, 18-month pharmacoepidemiological
      survey was conducted in the Department I of Internal Medicine at the University
      Hospital of Erlangen. All patients were intensively monitored for ADRs by a
      pharmacoepidemiological team. ADRs were evaluated for their offending drugs,
      probability, severity, preventability and classified by WHO-ART. During a 6-month
      period ADR-positive patients were matched to non-ADR patients applying diagnosis
      related group categorization in order to measure the impact of ADRs on the
      duration and frequency of hospitalization. RESULTS: Of 1000 admissions 424
      patients had single admissions and 206 patients had recurrent readmissions (min
      1, max 9). The prevalence of readmissions was 37% (n = 370). In 145 (23%) of 630
      patients, 305 ADRs were observed. The ADR incidence was similar in first
      admissions and readmissions. ADRs were not found to predict further readmissions
      and lack of ADRs did not preclude readmissions. ADRs caused hospitalizations in
      6.2% of first admissions and in 4.2% of readmissions. According to the Schumock
      algorithm 135 (44.3%) ADRs were found to be preventable. The occurrence and
      numbers of ADRs per admission were found to prolong hospitalization period
      significantly (r = 0.48 and 0.51, P < 0.001, n = 135). Of 9107 treatment days 20%
      were caused by in-house (1130 days) and community-acquired ADRs (669 days). In
      admissions and readmissions 11% (>973 days) of all treatment days were judged to
      be preventable. CONCLUSIONS: Intensified drug monitoring supported by information
      technology in internal medicine is essential for early detecting and prevention
      of ADRs and saving hospital resources.

PMID- 15147530
TI  - A prospective study on antibody response to repeated vaccinations with
      pneumococcal capsular polysaccharide in splenectomized individuals with special
      reference to Hodgkin's lymphoma.
AB  - BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming
      postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS)
      encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive
      prophylactic efforts the mortality and morbidity rates remain high. The present
      study was based on a strategy with a predefined vaccination algorithm including
      repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal
      antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL)
      patients were compared with those patients splenectomized due to immune-mediated
      cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic
      purpura (ITP)] and also individuals who were splenectomized because of trauma
      (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in
      this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their
      individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay
      technique the patients were revaccinated with 23-valent pneumococcal PS vaccine
      up to four times in accordance with the predefined algorithm. For each
      vaccination occasion, serum was collected at vaccination, after 1 month +/- 2
      weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a
      national population-based database, and microbiological databases were checked
      for 124 HL patients to identify OPSI. RESULTS: A significant response was
      recorded on primary vaccination as well as on two revaccination occasions for HL,
      AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time
      elapsed between splenectomy and first pneumococcal vaccination was found to be
      associated with mean PS antibody levels at prevaccination, peak or follow-up. No
      severe adverse events were reported. Amongst 124 clinically monitored HL
      patients, 10 OPSI were recorded in seven patients during the study period. One of
      these patients, a middle-aged female, died as a result of fulminant pneumococcal
      bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A
      significant response to pneumococcal PS vaccination was found in all three groups
      (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary
      and repeated vaccinations were safe. Until further knowledge is gained regarding
      the protective concentration of serotype-specific antibody concentrations we
      believe that the value of vaccination and frequent revaccination (every 1-5
      years) in combination with education of patients and health care professionals
      and clinical monitoring is beneficial for these patients at risk for OPSI.

PMID- 15147531
TI  - Isolated PACNS-like presentation of a systemic vasculitis complicating a
      myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are a series of haematological malignancies
      ranging from chronic refractory anaemia to leukaemia. There is increasing
      recognition of immunological abnormalities in patients with MDS, including few
      reports of cutaneous vasculitis; in no instance, a cerebral localization has been
      ascertained. Here, the case of a patient with MDS who presented exclusively with
      neurological signs that were considered indicative of a primary, isolated central
      nervous system vasculitis (PACNS) is reported. Although histological findings on
      brain tissue confirmed a small-vessel vasculitis, this had to be considered in
      the context of a systemic vasculitis. In fact, at autopsy, an involvement of
      skin, myocardium, lungs, liver, kidney and bone marrow was also found. An
      autoimmune vasculitis should be included in the differential diagnosis of acute
      onset, isolated, cerebral symptoms complicating the course of MDS.

PMID- 15147532
TI  - Coronary heart disease in a patient with cerebrotendinous xanthomatosis.
AB  - Coronary heart disease is a prevalent condition and a leading cause of death in
      developed countries. Most cases are due to the cluster of classical risk factors,
      such as smoking, diabetes, high blood pressure and dyslipidaemia. However, a few
      patients develop severe and premature arteriosclerosis in spite of absence of
      common risk factors. Here, we present the clinical, analytical and molecular
      features of a 36-years-old man who died from advanced ischaemic heart disease as
      a result of cerebrotendinous xanthomatosis (CTX), a rare condition characterized
      by elevation in plasma and most tissues of cholestanol and where neurological
      impairment is the hallmark of this disease. We discuss the relevance of heart
      disease and the mechanism leading to accelerate arteriosclerosis is CTX.

PMID- 15147533
TI  - Enrichment of HFE mutations in Swedish patients with familial and sporadic form
      of porphyria cutanea tarda.

PMID- 15147534
TI  - Four unrelated cases with Takayasu arteritis and CD36 deficiency: possible link
      between these disorders.

PMID- 15147535
TI  - Waist circumference versus body mass index in risk prediction of coronary heart
      disease: comparing apples and oranges.

PMID- 15147536
TI  - Colonic malignancy with recurrent bacteraemia presenting as pyrexia of unknown
      origin.

PMID- 15147537
TI  - No association of reported functional protein tyrosine phosphatase 1B 3' UTR gene
      polymorphism with features of the metabolic syndrome in a Swedish population.

PMID- 15147540
TI  - Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence
      after radical surgery.
AB  - BACKGROUND: The objective of the present study was to investigate the
      significance of microscopic venous invasion (MVI) as a prognostic factor for
      patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS:
      The study included a total of 157 consecutive patients with non-metastatic RCC
      who underwent radical surgery between January 1986 and December 2002. The median
      follow-up period was 45 months (range 6-162 months). Microscopic venous invasion
      was defined by the presence of a cancer cell in blood vessels based on the
      examination of hematoxylin-eosin stained specimens. Other prognostic variables
      were assessed by multivariate analysis to determine whether there was a
      significant impact on cancer-specific and recurrence-free survivals. RESULTS:
      Microscopic venous invasion was found in 70 patients, and of this number, 17
      (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression,
      while only six (6.9%) of the remaining 87 patients without MVI presented with
      disease-recurrence and three (3.5%) died of cancer. Among the factors examined,
      the presence of MVI was significantly associated with age, mode of detection,
      tumor size, pathological stage and tumor grade; however, only pathological stage
      was an independent predictor for disease-recurrence, and none of these factors
      were available to predict cancer-specific survival in multivariate analyses. In
      120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this
      subgroup, recurrence-free survival rates in patients with MVI were significantly
      lower than those in patients without MVI, and MVI was the only independent
      prognostic predictor for disease-recurrence in a multivariate analysis.
      CONCLUSION: Microscopic venous invasion is not an independent prognostic factor
      in patients with non-metastatic RCC who underwent radical surgery; however, it
      could be the only independent predictor of disease-recurrence after radical
      surgery for patients with pT1 or pT2 disease.

PMID- 15147539
TI  - Long-term outcome of postoperative interferon-alpha adjuvant therapy for non
      metastatic renal cell carcinoma.
AB  - AIM: To investigate the long-term efficacy of postoperative interferon-alpha (IFN
      alpha) adjuvant therapy in preventing recurrence in non-metastatic renal cell
      carcinoma treated with radical nephrectomy and to identify related prognostic
      markers. METHODS: Long-term follow-up was conducted to study rates of survival
      and non-recurrence in 88 subjects following radical nephrectomy for non
      metastatic disease. RESULTS: The overall survival rate was 90% at 5 years and 88%
      at 10, with corresponding non-recurrence rates of 81% and 74%. Survival rates
      reviewed by preadministration pT stage showed a falling tendency from T1 through
      to T3 in line with pathological progression; when cases at stage pT1b or below
      were compared with those at stage pT2 or above, the latter showed a tendency to
      lower survival rates (P = 0.0966, Breslow-Gehan-Wilcoxon). Similarly, non
      recurrence rates tended to fall in line with pathological progression, with a
      significant difference found in the comparison of cases at stage pT1b or below
      with those at stage pT2 or above (P = 0.0265, log-rank, Mantel-Cox). Duration of
      IFN-alpha administration showed a tendency to positive correlation with long-term
      survival (P = 0.3765, Breslow-Gehan-Wilcoxon). Non-recurrence rate was not found
      to differ according to duration of administration. Comparison of groups with
      normal and abnormal preadministration immunosuppressive acidic protein values
      showed that the normal group tended to have higher rates of survival and non
      recurrence (P = 0.3371, Breslow-Gehan-Wilcoxon). CONCLUSIONS: Immunosuppressive
      acidic protein values appear to be a useful predictive marker for recurrence. A
      randomized trial, examining long-term outcome according to tumor stage and
      variables such as duration of administration, dose, administration time, and
      dosing schedule is required.

PMID- 15147541
TI  - Multiple primary malignancies in Japanese patients with renal cell carcinoma.
AB  - AIM: To evaluate the incidence, nature and prognosis of multiple primary
      malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975
      and 1998, 319 patients underwent an operation for RCC at Hokkaido University,
      Sapporo, Japan. The incidence of other primary malignancies was determined and
      classified as antecedent, synchronous or subsequent. Follow-up was obtained by
      thorough chart review or telephone interview, and ranged from 0 to 276 months
      (median 49.0 months). To analyze the influence of other primary malignancies on
      prognosis, overall and cause-specific survival rates of the patients with an
      antecedent or synchronous malignancy were compared to the remaining patients.
      RESULTS: Of the 319 patients there was at least one other malignancy in 38
      patients (12%). Four patients had two other malignancies. The other malignancies
      were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty
      two patients had gastrointestinal cancer. In cases of antecedent or synchronous
      diagnosis of other primary malignancies, RCC was commonly incidental, small or
      low-stage. Multivariate analysis using Cox's proportional hazards model showed
      that, for overall survival, the presence of other antecedent or synchronous
      malignancies was the second most significant prognostic factor, following the
      pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the
      incidence of other primary malignancies was not uncommon and these malignancies
      contributed to the prognosis of these patients. Therefore, the malignant
      potential of individual tumors should be paid careful attention in the management
      of these patients.

PMID- 15147542
TI  - Characteristics of patients with staghorn calculi in our experience.
AB  - PURPOSE: To elucidate the factors contributing to staghorn stone formation in
      patients. MATERIALS AND METHODS: The records of 82 patients (44 men and 38 women)
      with complete staghorn calculi were reviewed retrospectively for clinical
      presentation, metabolic disturbances and anatomical abnormalities. RESULTS: There
      were 79 unilateral and three bilateral cases. The patient performance of the
      activities of daily life was assessed with the modified Rankin scale (MRS) and it
      was found that 69 patients were functionally independent (84.1%, MRS 0-1) and 10
      patients had a severe disability (12.2%, MRS 4-5). Seven patients had chronic
      indwelling catheters (8.5%). A positive urine culture was found in 24.4% of
      patients. Analysis of stone composition revealed magnesium ammonium phosphate and
      mixed calcium oxalate-phosphate were the most frequently identified types of
      stone (32.1% and 22.2%, respectively). Urinary pH was low in patients with uric
      acid stones (mean 5.4). Hyperuricemia, cystinuria and hypercalciuria were found
      in 14.6%, 2.4% and 37.8%, respectively. Hypercalciuria was found more frequently
      in calcium-stone cases. Eleven patients (13.4%) showed structural abnormalities
      of the kidney. CONCLUSIONS: Our data show that the patients with severe
      disability, urinary tract infection and hypercalciuria could be recognized more
      frequently in staghorn calculi compared with common urolithiasis. However, in
      Western countries, the frequency of both urinary tract infection and struvite
      stones is much higher than in our data. Other Japanese authors have also reported
      the low frequency of struvite stones in staghorn calculi, suggesting that various
      factors other than urinary tract infection possibly contribute to the formation
      of staghorn calculi in Japan.

PMID- 15147543
TI  - Prevalence of and risk factors for nocturia: Analysis of a health screening
      program.
AB  - BACKGROUND: We examined the prevalence of and risk factors for nocturia in
      Kurashiki city and the surrounding area, a rural area in Japan. MATERIALS AND
      METHODS: We collected data on 6517 individuals (4568 men and 1949 women) who
      participated in a multiphasic health screening. We analyzed the relationships
      between nocturia assessed by a questionnaire (voiding twice or more during night)
      and other variables including age, hypertension, cardiovascular disease,
      cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus
      (DM), chronic renal failure, benign prostatic hyperplasia (BPH), smoking habit
      and alcohol intake. RESULTS: Overall, 1856 individuals (28.5%) answered that they
      arose to urinate at least twice during the night. This rate increased with age
      from 16.5% in individuals younger than 50 to 60.0% in those older than 69.
      Logistic regression analysis revealed that cohorts of subjects 50-59, 60-69, and
      70 years old or over had, respectively, 1.75, 3.35, and 6.21 times the prevalence
      of nocturia of the 49 years or younger cohort. Hypertension (odds ratio [OR]
      1.64) and DM (OR 1.70) were other independent positive risk factors for nocturia.
      On the other hand, current smokers who smoked 20 or more cigarettes per day were
      less likely to have nocturia than non-smokers (OR 0.72). In male individuals, BPH
      was another independent positive risk factor (OR 1.35). Gender was not associated
      with nocturia. CONCLUSIONS: Although population bias is an important limitation
      to this study, nocturia is associated with various factors suggesting that
      multiple approaches are needed to the treatment of patients with nocturia.

PMID- 15147544
TI  - A pilot study evaluating a new questionnaire for prostatic symptom scoring, the
      SPSS, and its sensitivity as constructed to objective measures of outflow
      obstruction.
AB  - AIM: To evaluate the extent to which our newly developed questionnaire, the
      Saitama Prostate Symptom Score (SPSS), for prostatic symptom scoring reflects
      objective findings in benign prostatic hyperplasia (clinical BPH) and to compare
      it with the International Prostate Symptom Score (IPSS) with regard to diagnostic
      sensitivity in clinical BPH. METHODS: In this study, both the SPSS and the IPSS
      were self-administered by patients. Free uroflowmetry, a pressure-flow study and
      the measurement of prostatic volume were carried out. RESULTS: There was no
      significant correlation between the results of the IPSS questionnaire and the
      urethral obstruction grade estimated by Schaefer or Abrams-Griffiths nomograms.
      The total score of the SPSS was correlated with these nomograms (P = 0.0487 and P
      = 0.0413, respectively). There was no significant correlation between the results
      of the IPSS questionnaire and the total volume or transition zone volume of the
      prostate, whereas the total score of the SPSS correlated with the total volume of
      the gland and transition zone volume (P = 0.0044 and P= 0.0051, respectively).
      CONCLUSION: This study revealed the SPSS to correlate with objective findings
      satisfactorily. However, there are still several aspects of the SPSS which need
      to be improved upon, and the questionnaire should be studied in larger numbers of
      patients suffering from lower urinary tract symptoms.

PMID- 15147545
TI  - Radical prostatectomy and adjuvant endocrine therapy for prostate cancer with or
      without preoperative androgen deprivation: Five-year results.
AB  - BACKGROUND: The effects of preoperative androgen deprivation on the outcomes of
      prostate cancer patients who received radical prostatectomy and subsequent
      adjuvant endocrine therapy have not yet been fully evaluated. METHODS: Patients
      with stage A(2), B or C prostate cancers were randomized to one of two groups:
      group I (n = 90), who received androgen deprivation (leuprolide and chlormadinone
      acetate) for 3 months followed by radical prostatectomy and subsequent adjuvant
      endocrine therapy (leuprolide alone), and group II (n = 86), who underwent the
      surgery followed by 3-month androgen deprivation (leuprolide and chlormadinone
      acetate) and subsequent adjuvant endocrine therapy (leuprolide alone). The
      effects of preoperative androgen deprivation on survival, clinical relapse (serum
      prostate specific antigen, PSA, above the normal level, local recurrence, or
      distant metastases), and PSA relapse (PSA above the detectable level) were
      evaluated at 5 years or later after treatment. RESULTS: There were no significant
      differences in overall, cause-specific, clinical relapse-free, or PSA relapse
      free survival rates between the two groups. In a subanalysis, no prostate cancer
      deaths or clinical relapses were noted in 29 patients with organ-confined disease
      (OCD: negativity of capsular invasion, seminal vesicle invasion, surgical margins
      or nodal involvement). The odds ratio for OCD depending on group assignment was
      2.44 (95% confidence interval, CI 1.04-5.72), for group I, demonstrating a higher
      probability of having OCD. This ratio was increased to 4.00 (95% CI 1.06-15.16)
      if the analysis was conducted in a subpopulation with prostate specific antigen
      levels less than 35.6 ng/mL and with clinical stage B or C cancers. CONCLUSION:
      Preoperative androgen deprivation has no demonstrable benefit in 5-year outcomes
      for patients undergoing radical prostatectomy and adjuvant endocrine therapy.
      However, it did increase the probability of OCD, which was associated with no
      clinical relapse during the follow-up. A longer observation is needed to clarify
      the exact extent of the benefits in terms of survival.

PMID- 15147546
TI  - Retrospective study on stage B prostate cancer in the Hokuriku District, Japan.
AB  - BACKGROUND: The present study was conducted to investigate how patients with
      clinically localized prostate cancer were treated in the Hokuriku District,
      Japan. METHODS: Medical records of 536 patients with stage B prostate cancer were
      retrospectively reviewed. The patients were diagnosed and treated at four
      university hospitals and 32 collaborating hospitals in the Hokuriku District.
      RESULTS: Because their medical records were incomplete and/or they not available
      for follow up, 79 cases were excluded from this study. Conservative treatment
      with hormone therapy was used for 248 cases. Radical prostatectomy was performed
      in 199 cases, only 27 of whom underwent surgical monotherapy. There was no
      significant difference in disease-specific survival rates between the hormone
      (69.0%) and surgery group (83.2%) after 110 months. Results of the analysis of
      disease-specific survival rates according to histologic grade showed that
      patients with poorly differentiated cancers treated with hormone therapy were the
      only subset with significant differences when compared against the other
      patients. CONCLUSION: The value of prostatectomy alone or added was marginal in
      terms of survival. Only patients with poorly differentiated cancer might benefit
      from prostatectomy.

PMID- 15147547
TI  - A risk index for prostate cancer.
AB  - BACKGROUND: The aim of the present study was to create a simple numerical index
      predicting the presence of prostate cancer in a group of high risk patients, for
      the purpose of selecting those most likely to need prostate biopsy. METHODS: 100
      consecutive patients at high risk of having prostate cancer seen at Ramathibodi
      Hospital, Thailand between November 2000 and February 2002 were prospectively
      studied. All patients underwent transrectal prostate biopsies. The following
      predictor variables were obtained: age, digital rectal examination (DRE)
      findings, prostate specific antigen level, transrectal ultrasonography (TRUS)
      findings, and prostate volume determined by TRUS. The outcome was the presence of
      prostate cancer on histological examination of the biopsy specimens. A risk index
      for prostate cancer based on the linear predictor of a multiple logistic
      regression model was created. RESULTS: Almost all predictor variables were
      significantly related to the presence of prostate cancer. The final multiple
      logistic regression model with four categorized predictors (excluding DRE) was
      shown to have good discrimination, calibration, and cross-validity. For a cutoff
      risk index of 10, corresponding to a 10% probability of having prostate cancer,
      the sensitivity for detecting prostate cancer was 96.2%, with a specificity of
      73.0%. Based on this cutoff, 55% of patients in this series might not require
      prostate biopsy. CONCLUSION: A risk index for prostate cancer was developed. If
      this index can be externally validated, the potential savings from avoiding
      unnecessary prostate biopsies, on the basis of selection using the index, could
      be significant.

PMID- 15147548
TI  - Penile vascular abnormalities observed long-term after surgical repair of penile
      fractures.
AB  - AIM: To assess the penile vascular system in men long-term after surgical
      treatment of penile fractures. PATIENTS AND METHODS: During a 15-year period, 36
      cases of penile fracture underwent immediate surgical repair at the University of
      Istanbul, Turkey. At least 1 year after operation, all patients were invited for
      penile vascular evaluation. 15 patients accepted our call and were enrolled in
      our study. They were evaluated with detailed medical and sexual history, a serial
      of serum analyses, and penile color Doppler ultrasonography. RESULTS: By history,
      6 of the 36 (16.6%) patients who had undergone surgical repair had erectile
      dysfunction (ED). The mean interval between surgical intervention for penile
      fracture and penile vascular evaluation was 3.6 +/- 1.9 (range 1.5-8) years.
      Evaluation of the penile vascular system of 15 men (mean age 35.7 +/- 17.3, range
      21-63 years) revealed normal vascular system in seven (46.7%), while cavernosal
      insufficiency was observed in four (26.7%) and arterial insufficiency in three
      (20%) men. The remaining case (6.7%) was diagnosed to have mixed arterial and
      cavernous insufficiency. Erectile dysfunction in two cases was considered to be
      in psychogenic origin and vascular in the remaining four. CONCLUSION: Although
      immediate repair is reported to be the treatment of choice in penile fractures,
      ED of either a physiological or vascular origin can be encountered as a long-term
      sequel and deserves to be evaluated in detail.

PMID- 15147550
TI  - Adrenal myelolipoma associated with adenoma.
AB  - The association of an adrenal myelolipoma with a non-functioning adenoma is very
      rare. Herein, we report on such a case in an asymptomatic 64-year-old woman. To
      the best of our knowledge, there is only one other case of non-functioning
      adrenocortical adenoma associated with myelolipoma in the same gland.
      Furthermore, only two other adenomas (mineral corticoids and corticosteroid
      producing tumors) associated with myelolipomas have been reported, and both
      myelolipomas were less than 1 cm in size. In conclusion, the 8.5 cm myelolipoma
      in our case is the largest compared with the three previously reported ones.

PMID- 15147549
TI  - The neuronal and endothelium-dependent relaxing responses of human corpus
      cavernosum under physiological oxygen tension last longer than previously
      expected.
AB  - BACKGROUND: Intracavernosal oxygen tension varies greatly in the process of
      erection. Blood extracted from the human penis demonstrates an increase from
      approximately 30 mmHg Po(2) in the flaccid state to 100 mmHg in the erect state
      of the penis. In the present study, using these levels as a guide, we investigate
      how the NO-dependent relaxation of human corpus cavernosum changed under
      physiological oxygen tensions ranging from approximately 30 to 100 mmHg. METHODS:
      Human penile tissue specimens were obtained at penile surgery with informed
      consent from the patients. The preparations were mounted in Krebs solution in an
      organ bath and the isometric tension was recorded. Krebs solutions of various
      oxygen tensions were prepared by bubbling 5% CO(2) in N(2) and O(2). The NO
      dependent relaxation caused by electrical field stimulation (EFS) and
      acetylcholine (ACh) was studied, and the amplitude and duration of relaxation
      evaluated. RESULTS: The amplitude of relaxation induced by EFS was significantly
      decreased under physiological oxygen tension conditions (P < 0.01). The duration
      of the relaxant response induced by EFS and ACh was significantly prolonged in
      physiological oxygen tension conditions than in high oxygen tension (P < 0.01).
      However, there was no correlation between the duration of relaxation induced by
      EFS and each physiological oxygen tension level. The duration of relaxation
      induced by ACh was most prolonged at 60-69 mmHg oxygen tension. CONCLUSION:
      Physiologically, the effect of NO may last longer than was previously thought. In
      addition, it would seem that there is an optimal physiological oxygen tension for
      maximum ACh-induced relaxation.

PMID- 15147551
TI  - Local recurrence of a unilateral cystic nephroma.
AB  - Cystic nephroma is an uncommon, benign renal lesion. We report the first case of
      local recurrence of a unilateral cystic nephroma in an adult. Only three cases of
      recurrence in bilateral cystic nephroma have been described in the literature
      before. Other renal lesions may not be differentiated preoperatively from cystic
      nephroma and thus require surgical exploration. Long-term follow-up is
      recommended to rule out local recurrence.

PMID- 15147552
TI  - Retrospective analysis of 135 renal trauma cases.
AB  - BACKGROUND: We review our trauma cases over the last 11 years and discuss our
      diagnosis and treatment modalities. METHODS: One hundred and thirty-five patients
      with renal injuries who had been hospitalized in the Urology and General Surgery
      clinics of Dicle University hospital between 1990 and 2001 were reviewed
      retrospectively. Patients were evaluated with regard to age, sex, cause of
      trauma, transport time, diagnostic methods, grade of injuries, associated organ
      injuries, treatments and complications. RESULTS: One hundred and forty-one renal
      injuries were established in 135 patients. The patients were between 5 and 65
      years old; 114 (84.4%) were male and 21 (15.6%) were female. The most common
      cause of injuries (99 patients) was penetrating injuries. The transport time to
      hospital after injury was approximately 116 min. Immediate laparotomy was
      performed in 95 hemodynamically unstable patients. Radiological investigations
      were carried out in the remaining 40 patients. Most of the injuries were grade 4
      (28, 19.86%) or 5 (60, 42.55%). Isolated renal injury was established in only 22
      of 135 patients. Nephrorrhaphy was performed in 45 of 141 kidneys. Twelve injured
      kidneys were managed conservatively. Nephrectomy was performed in 66 of 141
      kidneys. The remaining injured kidneys were managed with different treatment
      methods. Twenty-nine (21.48%) patients were lost intraoperatively or during the
      early postoperative period. CONCLUSION: We believe that our rates of nephrectomy
      and mortality were high because of the long transport time, unsuitable transport
      type, frequent high grade and high rate of associated organ injuries.

PMID- 15147554
TI  - Successful bladder management for a pure urogenital sinus anomaly.
AB  - We report on a case of a pure urogenital sinus anomaly presented with bladder
      distention. A seven-day-old girl with an abdominal distension was referred to the
      Division of Urology, Hakodate Central Hospital, Hakodate, Japan. A common
      urogenital sinus without abnormalities in the labium, clitoris or anus was found.
      A computed tomography (CT) scan documented a distended bladder without
      hydrometrocolpos or hydroureteronephrosis. Cystography performed at 44 days
      revealed a large flaccid bladder without ureteral reflux. Urinary management by
      an indwelling urethral catheter was maintained until 3 months, when an endoscopic
      examination was performed and a stenotic urethral-type urogenital sinus with low
      confluence was diagnosed. Parents successfully instituted clean intermittent
      catheterization as a temporary urinary management, and postvoid residual urine
      gradually decreased. At 2 years of age, flap vaginoplasty was performed. In an
      urodynamic study performed postoperatively, the detrusor pressure during voiding
      was 40-50 cmH(2)O. The patient maintained spontaneous voiding without
      consequences. Appropriate urinary care is essential to prevent urological
      complications in cases with a pure urogenital sinus anomaly.

PMID- 15147555
TI  - Holmium laser core through internal urethrotomy with explantation of UroLume
      stent. An ideal approach for a complicated posterior urethral stricture.
AB  - Although the UroLume wallstent has been proven effective in the treatment of
      recurrent urethral stricture, obstruction may recur in some cases. A likely cause
      of obstruction is hyperplastic tissue reaction, which may necessitate the removal
      of the stent. The hyperplastic tissue reaction may be severe, resulting in a
      completely obliterative stricture. Stent removal with a completely obliterative
      stricture and the stent in situ is a tedious job, as there is no lumen in which
      to place the laser fiber to cut the stent wires. We report on a patient in whom a
      UroLume urethral stent was placed one year ago for post-traumatic recurrent
      bulbomembranous urethral stricture. The stricture recurred in spite of the stent
      in place and the lumen was finally completely obliterated. A holmium laser was
      used for core through internal urethrotomy and the explantation of the stent.

PMID- 15147553
TI  - Inflammatory pseudotumor of the kidney.
AB  - A 38-year-old man without prior contributory history presented complaining of a
      tumor in the left upper abdomen without tenderness. Suspecting renal cell
      carcinoma of the dark cell type, a nephrectomy was performed. Microscopic
      examination showed a proliferation of spindle cells containing numerous blood
      vessels. A diffuse infiltrate of lymphocytes and plasma cells was scattered
      throughout the lesion.

PMID- 15147556
TI  - Bilateral epididymal sarcoidosis presenting without radiographic evidence of
      intrathoracic lesion: Review of sarcoidosis involving the male reproductive
      tract.
AB  - Sarcoidosis is a multisystem disorder that rarely involves the genitourinary
      tract. To date, only 59 cases of histologically proven sarcoidosis involving the
      male reproductive tract have been reported in the literature. We present here a
      case of bilateral epididymal sarcoidosis without radiographic evidence of
      intrathoracic lesion. A 46-year-old man presented with a one-week history of
      painless bilateral scrotal swellings. Physical examination detected multiple
      elastic firm nodules on both sides of the scrotum which showed no tenderness. The
      nodules seemed to involve the entire bilateral epididymides. Some irregularly
      shaped hypoechoic masses in the bilateral epididymides were identified on gray
      scale ultrasonography. On magnetic resonance images, the bilateral epididymides
      were seen to be enlarged, heterogeneous and nodular without any signs of
      testicular involvement. The lesion showed a slightly high signal intensity on the
      T2-weighted image. Pathological evaluation following bilateral epididymectomy
      found non-caseating epithelioid cell granulomas with giant cells in epididymal
      tissue, thus confirming a diagnosis of sarcoidosis. Gallium-67 scanning showed
      additional small hot spots in the anterior chest wall and extremities. Open
      biopsy of a superficial papular lesion in the dermis of the right upper arm was
      performed and pathological findings indicated sarcoid granulomas. This report
      also includes a review of the literature pertaining to sarcoidosis of the male
      reproductive tract.

PMID- 15147557
TI  - A case of traumatic testicular torsion associated with a ruptured epididymis.
AB  - To salvage the testis, most urological surgeons advocate early exploration of
      enlarging scrotal masses or suspected testicular ruptures resulting from trauma.
      A case of testicular torsion within a hematoma, following blunt testicular trauma
      is presented, and we suggest that another indication for exploring a scrotal mass
      following blunt injury is to help establish an early diagnosis of torsion of the
      testicle.

PMID- 15147558
TI  - Simple testicular cyst: a rare cause of scrotal swelling in infancy.
AB  - A simple testicular cyst is a rare cause of scrotal swelling in infancy. Only 10
      cases have been reported in children less than two years of age in the English
      literature. Pathogenesis of the lesion is unclear. Preoperative diagnosis is
      possible using ultrasonography (US). Testis-sparing surgery with simple
      enucleation of the cyst has a favorable outcome. We report two patients with a
      simple testicular cyst, who were 9 and 8 months of age. The first case was
      referred with a presumptive diagnosis of hydrocele, and the second infant was
      admitted with a history of testicular swelling. Ultrasonography provided accurate
      preoperative diagnosis in both of the cases. The patients were successfully
      treated with testis-sparing surgery with outstanding long-term results. This
      unusual lesion of infancy should be considered in the differential diagnosis of a
      scrotal mass.

PMID- 15147560
TI  - Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell
      mediated anti-tumour responses.
AB  - Cytokines and their receptors represent key targets for therapeutic intervention.
      Ligands are being used to supplement cell numbers that become depleted as a
      result of disease (organ failure, infection) or subsequent disease treatments
      (i.e. chemotherapy). Conversely, the inhibition of target cell binding by
      cytokines is an established strategy for abrogating pathologic cellular
      activities common to many immunological diseases. Considerable effort in
      biomedical research is being focused on the cytokine families that play a
      dominant role in regulating immunity and then prioritizing each member for its
      therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is
      widely recognized for its central involvement in controlling lymphocyte function
      and is the most explored for medical utility. Collectively, these proteins (or
      their antagonists) are either marketed drugs or have received advanced testing
      for an impressive array of indications including cancer, infectious disease,
      transplantation, inflammation and allergic asthma. Here we review the current
      understanding of IL-21, the most recent member of this cytokine family to be
      discovered. As will be discussed, IL-21 shares many of the same attributes as its
      relatives in that it has broad immunoregulatory activity and can modulate both
      humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour
      responses in mice defines one therapeutic indication that merits clinical
      development.

PMID- 15147559
TI  - Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes.
AB  - The ezrin/radixin/moesin (ERM) family of actin-binding proteins act both as
      linkers between the actin cytoskeleton and plasma membrane proteins and as signal
      transducers in responses involving cytoskeletal remodelling. The Rho family of
      GTPases also regulate cytoskeletal organisation, and several molecular pathways
      linking ERM proteins and Rho GTPases have been described. This review discusses
      recent findings on ERM protein function in leucocytes and how these may be
      integrated with Rho GTPase signalling.

PMID- 15147561
TI  - Tethered ligand-derived peptides of proteinase-activated receptor 3 (PAR3)
      activate PAR1 and PAR2 in Jurkat T cells.
AB  - Proteinase-activated receptors (PARs) can activate a number of signalling events,
      including T-cell signal-transduction pathways. Recent data suggest that the
      activation of PARs 1, 2 and 3 in Jurkat T-leukaemic cells induces tyrosine
      phosphorylation of the haematopoietic signal transducer protein, VAV1. To
      activate the PARs, this study used the agonist peptides SFLLRNPNDK, SLIGKVDGTS
      and TFRGAPPNSF, which are based on the sequences of the tethered ligand sequences
      of human PARs 1, 2 and 3, respectively. Here, we show that peptides based on
      either the human or murine PAR(3)-derived tethered ligand sequences (TFRGAP-NH(2)
      or SFNGGP-NH(2)) do not activate PAR(3), but rather activate PARs 1 and 2, either
      in Jurkat or in other PAR-expressing cells. Furthermore, whilst thrombin
      activates only Jurkat PAR(1), trypsin activates both PARs 1 and 2 and also
      disarms Jurkat PAR(1) for thrombin activation. We conclude therefore that in
      Jurkat or related T cells, signalling via PARs that can affect VAV1
      phosphorylation is mediated via PAR 1 or 2, or both, and that distinct serine
      proteinases may potentially differentially affect T-cell function in the settings
      of inflammation.

PMID- 15147562
TI  - Impaired chemokine-induced migration during T-cell development in the absence of
      Jak 3.
AB  - The arrival of bone marrow T-cell progenitors to the thymus, and the directed
      migration of thymocytes, are thought to be regulated by the expression of
      chemokines and their receptors. Recent data has shown that the Jak/Stat
      signalling pathway is involved in chemokine receptor signalling. We have
      investigated the role of Jak 3 in chemokine-mediated signalling in the thymus
      using Jak 3(-/-) mice. These mice show defects in T-cell development, as well as
      in peripheral T-cell function, resulting in a hypoplastic thymus and an altered T
      cell homeostasis. Here we demonstrate, for the first time, that bone marrow
      progenitors and thymocytes from Jak 3(-/-) mice have decreased chemotactic
      responses to CXCL12 and CCL25. We also show that Jak 3 is involved in signalling
      through CCR9 and CXCR4, and that specific inhibition of Jak 3 in wild-type
      progenitors and thymocytes decreases their chemotactic responses towards CCL25
      and CXCL12. Finally, quantitative reverse transcription-polymerase chain reaction
      analysis showed that thymocytes from Jak 3(-/-) mice express similar levels of
      CXCR4 and CCR9 compared to wild-type mice. Altogether, deficient CCL25- and
      CXCL12-induced migration could result in a homing defect of T-cell progenitors to
      the thymus, as well as in a deficient thymocyte migration through the thymic
      stroma. Our results strongly suggest that the absence of Jak 3 affects T-cell
      development, not only through an impaired interleukin-7 receptor (IL-7R)-mediated
      signalling, but also through impaired chemokine-mediated responses, which are
      crucial for thymocyte migration and differentiation.

PMID- 15147563
TI  - The mechanism for activation of the neutrophil NADPH-oxidase by the peptides
      formyl-Met-Leu-Phe and Trp-Lys-Tyr-Met-Val-Met differs from that for interleukin
      8.
AB  - Neutrophil chemotaxis has been shown to be regulated by two different signalling
      pathways that allow strong chemoattractants, such as bacterial-derived formylated
      peptides, to dominate over endogenous attractants, such as interleukin-8 (IL-8).
      Here we show that triggering of the formyl peptide receptor (FPR) with f-Met-Leu
      Phe (fMLF) substantially reduced the neutrophil superoxide production induced by
      activation of the CXC receptors with IL-8. When the order of agonists was
      reversed, the cells were primed in their response to fMLF, suggesting that the
      signalling hierarchy between strong, so-called end-type (i.e. fMLF) and weak or
      intermediate-type (i.e. IL-8) chemoattractants, is also operating during
      activation of the NADPH-oxidase. The same result was obtained when fMLF was
      replaced with the hexapeptide, WKYMVM, specific for the formyl peptide-like
      receptor 1 (FPRL1). There were additional differences between the agonist
      receptor pairs fMLF/FPR, WKYMVM/FPRL1 and IL-8/CXCR. In contrast to FPR and
      FPRL1, no reserve pool of CXCR was present in subcellular granules and it was
      impossible to prime the oxidative response transduced through CXCR by the
      addition of priming agents such as tumour necrosis factor-alpha and platelet
      activating factor. Moreover, the cytoskeleton-disrupting substance, cytochalasin
      B, had no effect either on IL-8-triggered oxidase activation or on CXCR
      reactivation. A pertussis toxin-sensitive G-protein is involved in signalling
      mediated through both FPR and CXCR, and the signalling cascades include a
      transient intracellular calcium increase, as well as downstream p38 MAPK and
      phosphoinositide 3-kinase activation. The data presented in this study provide
      support for two different signalling pathways to the neutrophil NADPH-oxidase,
      used by ligand binding to FPR/FPRL1 or CXCR, respectively.

PMID- 15147564
TI  - Efficient scavenger receptor-mediated uptake and cross-presentation of negatively
      charged soluble antigens by dendritic cells.
AB  - Exogenous antigens endocytosed in large amounts by antigen-presenting cells (APC)
      are presented on major histocompatibility complex (MHC) class I molecules as well
      as on class II molecules, a process called cross-presentation. Among APC,
      dendritic cells (DC) play a key role in cross-presentation by transporting
      internalized antigen to the cytosol. The present study shows that ovalbumin (OVA)
      introduced with negative charges by succinylation (Suc-OVA), maleylation (Mal
      OVA) or cis-aconitylation (Aco-OVA) was efficiently taken up by DC via scavenger
      receptors (SR). Mal-OVA and Aco-OVA were efficiently cross-presented by DC, while
      cross-presentation of Suc-OVA was hardly observed. MHC class I presentation of
      acylated OVA introduced directly into the cytosol was inefficient and
      presentation of exogenous native OVA but not of Aco-OVA was markedly augmented by
      chloroquine, an inhibitor of endosomal acidification, suggesting that deacylation
      in endosomes or lysosomes is necessary for cross-presentation of acylated OVA.
      MHC class I presentation of exogenous native OVA and Aco-OVA by DC was blocked by
      lactacystin and brefeldin A, demonstrating that exogenous antigens taken up by DC
      are cross-presented through the conventional cytosolic pathway. Therefore, SR
      mediated delivery of antigen to DC leads to efficient cross-presentation,
      although the pathway of chemical modification should be considered.

PMID- 15147566
TI  - Selective killing of B-cell hybridomas targeting proteinase 3, Wegener's
      autoantigen.
AB  - Wegener's granulomatosis (WG) is a rare disease characterized by granulomatous
      lesions, small vessel vasculitis and the presence of anti-neutrophil cytoplasmic
      autoantibodies (C-ANCAs) in the sera of affected patients. Their main target
      antigen is proteinase 3 (PR3), a neutrophil and monocyte-derived neutral serine
      protease. Since the standard treatment of this severe autoimmune disease, with
      cyclophosphamide and corticosteroids, is associated with potential side-effects,
      the development of a more specific immunotherapeutic agent is warranted. The key
      role of ANCA in the pathogenesis of vasculitis and the effectiveness of anti-CD20
      antibodies in patients with refractory WG points towards the importance of B
      cells in WG. We thus evaluated a new approach to selectively eliminate PR3
      specific autoreactive B cells by targeting the B-cell receptor. For this purpose
      we used a bifunctional recombinant fusion protein consisting of the antigen PR3
      and a toxin. The cytotoxic component of this novel fusion protein was the
      ribonuclease angiogenin, a human toxin with low immunogenicity. The toxin was
      stabilized by exchanging the catalytically relevant histidine in position 44 with
      glutamine to eliminate the autoproteolytic activity. PR3H44Q was fused either to
      the N terminus or to the C terminus of angiogenin. The recombinant proteins were
      expressed in 293T cells. Binding assays demonstrated the appropriate size and
      recognition by anti-PR3 antibodies. Using TUNEL technology, we demonstrated that
      these autoantigen toxins kill proteinase 3-specific B-cell hybridomas selectively
      by inducing apoptosis. The data indicate that autoantigen-toxins are promising
      tools in the treatment or co-treatment of autoimmune diseases in which the
      antigen is known.

PMID- 15147565
TI  - Irradiation up-regulates CD80 expression through two different mechanisms in
      spleen B cells, B lymphoma cells, and dendritic cells.
AB  - We have previously demonstrated irradiation-induced up-regulation of CD80
      expression in A20-HL B lymphoma cells by inducing expression of tumour necrosis
      factor-alpha (TNF-alpha) and CD154. In the present study, we investigated whether
      irradiation also up-regulates CD80 expression in mouse spleen B cells. Because
      freshly prepared spleen B cells are highly sensitive to irradiation, we employed
      spleen B cells stimulated with lipopolysaccharide (LPS-B cells). X-irradiation (8
      Gy) followed by incubation (9-12 hr) highly and selectively up-regulated CD80
      expression in LPS-B cells, whereas the same treatment slightly increased
      expression of CD54 and did not affect expression of CD86, major
      histocompatibility complex class II, CD11a or surface immunoglobulin M. The
      irradiation-induced up-regulation of CD80 expression resulted in enhanced APC
      function of LPS-B cells. Up-regulation of CD80 expression on LPS-B cells was
      accompanied by an increase in CD80 mRNA accumulation and nuclear factor (NF)
      kappaB activation. Activation of NF-kappaB was shown to be critical for up
      regulation of CD80 expression as pyrrolidine dithiocarbamate (PDTC), an inhibitor
      of NF-kappaB, severely decreased the observed up-regulation. X-irradiation of LPS
      B cells induced expression of TNF-alpha but not CD154. However, anti-TNF-alpha
      monoclonal antibody (mAb) with anti-CD154 mAb did not inhibit X-irradiation
      induced up-regulation of CD80 expression in LPS-B cells, whereas these mAbs
      almost completely inhibited this up-regulation in A20-HL cells and bone marrow
      derived dendritic cells (DCs). In contrast, a thiol antioxidant, N-acetyl-l
      cysteine, completely blocked X-irradiation-induced up-regulation of CD80
      expression in LPS-B cells, but not in A20-HL cells or in DCs. Based on these
      findings, we concluded that X-irradiation up-regulates CD80 expression not only
      in A20-HL cells and DCs but also in LPS-B cells, and that this up-regulation in
      LPS-B cells via NF-kappaB activation is dependent on the generation of reactive
      oxygen species, while that in A20-HL cells and DCs is not.

PMID- 15147567
TI  - Sequence-specific binding of normal serum immunoglobulin M to exposed protein C
      termini.
AB  - Both the timely clearance of degraded endogenous structures and the presence of
      secreted natural immunoglobulin M (IgM) are needed to avoid autoimmunity. These
      requirements may be causally related provided that natural IgM preferentially
      reacts with degraded antigens and, by activating complement, mediates their non
      inflammatory clearance through complement receptors. We have previously shown
      that normal serum IgM reacts in vivo and in vitro with virtually all randomly
      generated C-terminal peptides displayed on T7 phage. The resultant multivalent
      IgM-peptide complexes activate complement and are detected by a loss of phage
      infectivity. A striking feature of these reactions is that different C-terminal
      peptides ( approximately 3-4 amino acids) specifically react with different 'C
      terminal' IgM (C-IgM) antibodies. This suggests that degraded supramolecular
      structures, expressing elevated levels of identical C-termini as a result of
      proteolysis, denaturation and abnormal exposure of repetitive protein
      constituents, may be preferential targets of C-IgM-mediated complement activation
      in the physiological environment. The specificity of C-IgM-peptide reactions is
      much higher than one would expect, assuming that normal serum IgM mostly
      comprises polyspecific natural antibodies. However, it is possible that
      polyspecific IgM is not adequately registered by our 'functional' phage
      inactivation assays. In this study, we resolve the issue of C-IgM specificity by
      directly characterizing the binding reactivity of normal serum IgM with phage
      displayed C-terminal peptides.

PMID- 15147568
TI  - Classical and alternative pathway complement activation are not required for
      reactive systemic AA amyloid deposition in mice.
AB  - During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice,
      either by chronic inflammation or by severe acute inflammation following
      injection of amyloid enhancing factor, the earliest deposits form in a
      perifollicular distribution in the spleen. Because the splenic follicular
      localization of immune complexes and of the scrapie agent are both complement
      dependent in mice, we investigated the possible complement dependence of AA
      amyloid deposition. In preliminary experiments, substantial depletion of
      circulating C3 by cobra venom factor had little effect on experimental amyloid
      deposition. More importantly, mice with targeted deletion of the genes for C1q or
      for both factor B and C2, and therefore unable to sustain activation,
      respectively, of either the classical complement pathway or both the classical
      and alternative pathways, showed amyloid deposition similar to wild type
      controls. Complement activation by either the classical or alternative pathways
      is thus not apparently necessary for the experimental induction of systemic AA
      amyloid in mice.

PMID- 15147569
TI  - Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum
      amyloid P component gene: SAP deficiency or strain combination?
AB  - Human serum amyloid P component (SAP) binds avidly to DNA, chromatin and
      apoptotic cells in vitro and in vivo. 129/Sv x C57BL/6 mice with targeted
      deletion of the SAP gene spontaneously develop antinuclear autoantibodies and
      immune complex glomerulonephritis. SAP-deficient animals, created by backcrossing
      the 129/Sv SAP gene deletion into pure line C57BL/6 mice and studied here for the
      first time, also spontaneously developed broad spectrum antinuclear autoimmunity
      and proliferative immune complex glomerulonephritis but without proteinuria,
      renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP
      gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells
      and isolated chromatin were more immunogenic in SAP(-/-) mice than in wild-type
      mice. In contrast, SAP-deficient pure line 129/Sv mice did not produce
      significant autoantibodies either spontaneously or when immunized with extrinsic
      chromatin or apoptotic cells, indicating that loss of tolerance is markedly
      strain dependent. However, SAP deficiency in C57BL/6 mice only marginally
      affected plasma clearance of exogenous chromatin and had no effect on
      distribution of exogenous nucleosomes between the liver and kidneys, which were
      the only tissue sites of catabolism. Furthermore, transgenic expression of human
      SAP in the C57BL/6 SAP knockout mice did not abrogate the autoimmune phenotype.
      This may reflect the different binding affinities of mouse and human SAP for
      nuclear autoantigens and/or the heterologous nature of transgenic human SAP in
      the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency
      and caused by expression of 129/Sv chromosome 1 genes in the C57BL/6 background.

PMID- 15147570
TI  - Contribution of alphabeta and gammadelta T cells to the generation of primary
      immunoglobulin G-driven autoimmune response in immunoglobulin- mu-deficient/lpr
      mice.
AB  - Class switch recombination (CSR) is a T-cell-dependent mechanism regulating
      isotype switching in activated mature B cells. Recently we showed that T-cell
      independent CSRs occur spontaneously during B lymphopoiesis, but such cells are
      negatively selected by Fas signalling. In immunoglobulin mu-deficient mice, lack
      of Fas rescues isotype-switched B cells, resulting in generation of an autoimmune
      primary immunoglobulin G (IgG) repertoire in muMT/lpr mice. In the present study,
      we studied the role of alphabeta and gammadelta T cells in regulating this
      primary gammaH-driven repertoire. We found that a lack of alphabeta T cells
      significantly inhibited IgG production and autoimmunity in muMT/lpr mice, whereas
      a lack of gammadelta T cells resulted in augmented IgG production and
      autoimmunity. Also, a lack of T cells in muMT mice rescued isotype-switched B
      cells and serum IgG, probably owing to the lack of available FasL. We suggest
      that although CSRs in B-cell lymphopoiesis are T-cell independent, alphabeta T
      cells are important in the expansion of isotype-switched B-cell precursors and in
      promoting gammaH-driven autoimmunity, whereas gammadelta T cells regulate these
      cells.

PMID- 15147572
TI  - Semen activates the female immune response during early pregnancy in mice.
AB  - Insemination elicits inflammatory changes in female reproductive tissues, but
      whether this results in immunological priming to paternal antigens or influences
      pregnancy outcome is not clear. We have evaluated indices of lymphocyte
      activation in lymph nodes draining the uterus following allogeneic mating in mice
      and have investigated the significance of sperm and plasma constituents of semen
      in the response. At 4 days after mating, there was a 1b7-fold increase in the
      cellularity of the para-aortic lymph node (PALN) compared with virgin controls.
      PALN lymphocytes were principally T and B lymphocytes, with smaller populations
      of CD3(+) B220(lo), NK1.1(+) CD3(-) (NK) and NK1.1(+) CD3(+) (NKT) cells. CD69
      expression indicative of activation was increased after mating and was most
      evident in CD3(+) and NK1.1(+) cells. Synthesis of cytokines including
      interleukin-2, interleukin-4 and interferon-gamma was elevated in CD3(+) PALN
      cells after exposure to semen, as assessed by intracellular cytokine fluorescence
      activated cell sorting, immunohistochemistry and quantitative reverse
      transcriptase polymerase chain reaction. Matings with vasectomized males
      indicated that the lymphocyte activation occurs independently of sperm. However,
      in contrast, males from which seminal vesicle glands were surgically removed
      failed to stimulate PALN cell proliferation or cytokine synthesis. Adoptive
      transfer experiments using radiolabelled lymphocytes from mated mice showed that
      lymphocytes activated at insemination home to embryo implantation sites in the
      uterus as well as other mucosal tissues and lymph nodes. These findings indicate
      that activation and expansion of female lymphocyte populations occurs after
      mating, and is triggered by constituents of seminal plasma derived from the
      seminal vesicle glands. Moreover, lymphocytes activated at insemination may help
      mediate maternal tolerance of the conceptus in the implantation site.

PMID- 15147573
TI  - Ectopic expression of CCL19 impairs alloimmune response in mice.
AB  - Initiation of an antitumour immune response is characterized by a complex process
      of chemokine-mediated cell migration and cell-cell interactions. Overexpression
      of chemokine CCL19 in tumour cells has been shown to result in accelerated tumour
      rejection under certain experimental conditions, suggesting a novel approach in
      the therapy of neoplastic malignancies. To investigate CCL19-mediated modulations
      of cellular immune responses in vivo, we generated a chimeric CCL19
      immunoglobulin G2b (IgG2b) Fc fusion protein, which binds to the chemokine
      receptor CCR7 comparable to native CCL19. CCL19-IgG2b possesses a long-lasting
      potent chemotactic activity as a result of the extended half-life of Fc fusion
      proteins. Stable overexpression of CCL19-IgG2b in BALB/c-derived J558L tumour
      cells fails to support tumour cell rejection following transplantation in
      syngeneic mice. Moreover, overexpression of CCL19-IgG2b hinders tumour rejection
      in allogeneic C57BL/6 mice. This phenomenon was accompanied by a six-fold
      increase of dendritic cells (DCs) isolated from CCL19-IgG2b-secreting tumours
      when compared to the number of DCs isolated from control parental J558L tumours.
      While mice bearing the allogeneic parental tumour showed an intense
      hypercellularity in the draining lymph nodes, no such response could be observed
      in the draining lymph nodes of mice carrying the CCL19-IgG2b-secreting tumour. We
      could demonstrate that overexpression of CCL19-IgG2b in tumour cells retains
      antigen-presenting cells in the tumour mass and prevents DCs from migrating into
      draining lymph nodes to present antigens and to activate T cells, resulting in an
      impaired immune response against the tumour.

PMID- 15147571
TI  - Aberration of CCR7 CD8 memory T cells from patients with systemic lupus
      erythematosus: an inducer of T helper type 2 bias of CD4 T cells.
AB  - Chemokine receptors are important in the entry of leucocytes into the
      inflammatory sites of systemic lupus erythematosus (SLE). CCR7(+) and CCR7(-)
      memory T cells exert different functions in homing, cytokine production and
      cytotoxicity. To determine whether differential expression and functions of the
      CCR7 occur in SLE patients, we examined CCR3, CCR4, CCR5, CCR7 and CCR9 on CD4(+)
      and CD8(+) T cells from normal and SLE subjects. Flow cytometry, real-time
      quantitative reverse transcription polymerase chain reactions and Northern
      blotting were used to detect the expression of chemokine receptors and cytokines;
      a chemotaxis assay was used to detect their functions. CD4(+) T-cell stimulation
      with syngeneic CCR7(+) CD8(+) CD45RO(+) T cells and dendritic cells (including
      transwell chambers) was used to induce cytokine expression. We demonstrated that
      CCR7 was selectively, frequently and functionally expressed on CD8(+) (94.8%) but
      not on CD4(+) (16.1%) T cells from patients with active SLE, whereas this
      phenomenon was not seen in normal subjects and in those whose SLE was inactive.
      CCR7(+) CD8(+) CD45RO(+) memory T cells from patients with active SLE, themselves
      T helper type 2 (Th2) biased, were inducers of Th2 bias in CD4(+) T cells in a
      cell-cell contact manner in vitro, meanwhile, the cells from both normal subjects
      and those whose SLE was inactive drove CD4(+) T cells into a regulatory T-cell
      derived cytokine pattern. Our findings might provide new clues to understanding
      the functions of CCR7(+) CD8(+) CD45RO(+)'central' memory T cells in autoimmune
      diseases (such as SLE). We suggest that in the case of active SLE, CCR7(+)
      central memory T cells were able to enter peripheral blood and inflammatory sites
      from secondary lymphoid organs, were continuously expressing CCR7, and interacted
      with dendritic cells and functioned as CCR7(-)'effector' memory T cells, which
      were described in normal humans.

PMID- 15147574
TI  - Differential effect of immune cells on non-pathogenic Gram-negative bacteria
      induced nuclear factor-kappaB activation and pro-inflammatory gene expression in
      intestinal epithelial cells.
AB  - We have previously shown that non-pathogenic Gram negative bacteria induce RelA
      phosphorylation, nuclear factor (NF)-kappaB transcriptional activity and pro
      inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in
      vitro. In this study, we investigated the molecular mechanism of immune
      epithelial cell cross-talk on Gram-negative enteric bacteria-induced NF-kappaB
      signalling and pro-inflammatory gene expression in IEC using HT-29/MTX as well as
      CaCO-2 transwell cultures Interestingly, while differentiated HT-29/MTX cells are
      unresponsive to non-pathogenic Gram negative bacterial stimulation, interleukin-8
      (IL-8) mRNA accumulation is strongly induced in Escherichia coli- but not
      Bacteroides vulgatus-stimulated IEC cocultured with peripheral blood (PBMC) and
      lamina propria mononuclear cells (LPMC). The presence of PBMC triggered both E.
      coli- and B. vulgatus-induced mRNA expression of the Toll-like receptor-4
      accessory protein MD-2 as well as endogenous IkappaBalpha phosphorylation,
      demonstrating similar capabilities of these bacteria to induce proximal NF-kappaB
      signalling. However, B. vulgatus failed to trigger IkappaBalpha degradation and
      NF-kappaB transcriptional activity in the presence of PBMC. Interestingly, B.
      vulgatus- and E. coli-derived lipopolysaccharide-induced similar IL-8 mRNA
      expression in epithelial cells after basolateral stimulation of HT-29/PBMC
      cocultures. Although luminal enteric bacteria have adjuvant and antigenic
      properties in chronic intestinal inflammation, PBMC from patients with active
      ulcerative colitis and Crohn's disease differentially trigger epithelial cell
      activation in response to E. coli and E. coli-derived LPS. In conclusion, this
      study provides evidence for a differential regulation of non-pathogenic Gram
      negative bacteria-induced NF-kappaB signalling and IL-8 gene expression in IEC
      cocultured with immune cells and suggests the presence of mechanisms that assure
      hyporesponsiveness of the intestinal epithelium to certain commensally enteric
      bacteria.

PMID- 15147575
TI  - Induction of immune responses against human papillomaviruses by hypervariable
      epitope constructs.
AB  - An ideal prophylactic vaccine against human papillomaviruses (HPV) would be one
      that can induce broadly reactive antibody titres to at least the major oncogenic
      strains of HPV. It has been previously shown that HPV structural proteins are
      highly immunogenic but fail to elicit cross-reactive immune responses against
      heterologous strains of HPV. Recent studies have demonstrated that the immunity
      induced by virus-like particles is mostly type specific. In the present study, we
      determined the breadth of reactivity of antibodies induced in mice immunized with
      hypervariable epitope constructs (HECs), which represent sequence variants of
      immunodominant B-cell epitopes of the major capsid protein L1 of HPV. In order to
      test the breadth of reactivity, sera from immunized mice were tested against
      peptides representing analogous sequences of HPV types 16, 18, 31 and 45. Mice
      immunized with HECs based on two epitopes mounted antibody responses that cross
      reacted with two different analogues, 16 and 18. Significantly, antibodies from
      mice immunized with HECs also inhibited haemagglutination mediated by HPV-16 L1
      VLPs, suggesting that immunization resulted in the development of antibodies that
      could bind to viral capsid proteins in their native conformation. Our
      observations suggest that HECs may overcome the restriction of type specific
      immunity against HPV.

PMID- 15147578
TI  - An approach to large scale identification of non-obvious structural similarities
      between proteins.
AB  - BACKGROUND: A new sequence independent bioinformatics approach allowing genome
      wide search for proteins with similar three dimensional structures has been
      developed. By utilizing the numerical output of the sequence threading it
      establishes putative non-obvious structural similarities between proteins. When
      applied to the testing set of proteins with known three dimensional structures
      the developed approach was able to recognize structurally similar proteins with
      high accuracy. RESULTS: The method has been developed to identify pathogenic
      proteins with low sequence identity and high structural similarity to host
      analogues. Such protein structure relationships would be hypothesized to arise
      through convergent evolution or through ancient horizontal gene transfer events,
      now undetectable using current sequence alignment techniques. The pathogen
      proteins, which could mimic or interfere with host activities, would represent
      candidate virulence factors. The developed approach utilizes the numerical
      outputs from the sequence-structure threading. It identifies the potential
      structural similarity between a pair of proteins by correlating the threading
      scores of the corresponding two primary sequences against the library of the
      standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity
      in distinguishing protein pairs with high structural similarity. CONCLUSION:
      Preliminary results obtained by comparison of the genomes of Homo sapiens and
      several strains of Chlamydia trachomatis have demonstrated the potential
      usefulness of the method in the identification of bacterial proteins with known
      or potential roles in virulence.

PMID- 15147579
TI  - Graphical technique for identifying a monotonic variance stabilizing
      transformation for absolute gene intensity signals.
AB  - BACKGROUND: The usefulness of log2 transformation for cDNA microarray data has
      led to its widespread application to Affymetrix data. For Affymetrix data, where
      absolute intensities are indicative of number of transcripts, there is a
      systematic relationship between variance and magnitude of measurements.
      Application of the log2 transformation expands the scale of genes with low
      intensities while compressing the scale of genes with higher intensities thus
      reversing the mean by variance relationship. The usefulness of these
      transformations needs to be examined. RESULTS: Using an Affymetrix GeneChip
      dataset, problems associated with applying the log2 transformation to absolute
      intensity data are demonstrated. Use of the spread-versus-level plot to identify
      an appropriate variance stabilizing transformation is presented. For the data
      presented, the spread-versus-level plot identified a power transformation that
      successfully stabilized the variance of probe set summaries. CONCLUSION: The
      spread-versus-level plot is helpful to identify transformations for variance
      stabilization. This is robust against outliers and avoids assumption of models
      and maximizations.

PMID- 15147576
TI  - Modulation of immune responses to bovine herpesvirus-1 in cattle by immunization
      with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154.
AB  - The objective of this study was to determine whether a DNA vaccine encoding
      bovine CD154 linked to a truncated version of bovine herpesvirus-1 (BHV-1)
      glycoprotein D (tgD-CD154) induces enhanced tgD-specific immune responses in
      cattle. In vitro characterization demonstrated that tgD and tgD-CD154 both bind
      to cultured bovine B cells, whereas only tgD-CD154 induces interleukin-4
      dependent proliferation, suggesting that tgD-CD154 specifically binds the CD40
      receptor and induces receptor signalling. Calves were immunized with plasmid
      encoding either tgD or tgD-CD154 by intradermal injection with a needle-free
      device. After two immunizations, tgD-specific immune responses were observed in
      both vaccinated groups and after challenge with BHV-1 these responses further
      increased. Animals immunized with plasmid encoding tgD-CD154 had significantly
      higher tgD-specific serum titres of immunoglobulins G and A but significantly
      lower numbers of tgD-specific interferon-gamma-secreting cells than animals
      immunized with plasmid encoding tgD after BHV-1 challenge. This suggests that the
      expression of an antigen as a chimeric protein with CD154 can qualitatively alter
      immune responses in cattle. Since we previously showed that plasmid encoding tgD
      CD154 induces significantly enhanced secondary tgD-specific antibody responses in
      sheep, there appear to be interspecies differences in the immune responses
      induced by tgD-CD154, which suggests that both proteins in the chimeric molecule
      may influence protein targeting and the induction of an immune response.

PMID- 15147580
TI  - Characterization of a nudix hydrolase from Deinococcus radiodurans with a marked
      specificity for (deoxy)ribonucleoside 5'-diphosphates.
AB  - BACKGROUND: Nudix hydrolases form a protein family whose function is to hydrolyse
      intracellular nucleotides and so regulate their levels and eliminate potentially
      toxic derivatives. The genome of the radioresistant bacterium Deinococcus
      radiodurans encodes 25 nudix hydrolases, an unexpectedly large number. These may
      contribute to radioresistance by removing mutagenic oxidised and otherwise
      damaged nucleotides. Characterisation of these hydrolases is necessary to
      understand the reason for their presence. Here, we report the cloning and
      characterisation of the DR0975 gene product, a nudix hydrolase that appears to be
      unique to this organism. RESULTS: The DR0975 gene was cloned and expressed as a
      20 kDa histidine-tagged recombinant product in Escherichia coli. Substrate
      analysis of the purified enzyme showed it to act primarily as a phosphatase with
      a marked preference for (deoxy)nucleoside 5'-diphosphates (dGDP > ADP > dADP >
      GDP > dTDP > UDP > dCDP > CDP). Km for dGDP was 110 microM and kcat was 0.18 s-1
      under optimal assay conditions (pH 9.4, 7.5 mM Mg2+). 8-Hydroxy-2'-deoxyguanosine
      5'-diphosphate (8-OH-dGDP) was also a substrate with a Km of 170 microM and kcat
      of 0.13 s-1. Thus, DR0975 showed no preference for 8-OH-dGDP over dGDP. Limited
      pyrophosphatase activity was also observed with NADH and some (di)adenosine
      polyphosphates but no other substrates. Expression of the DR0975 gene was
      undetectable in logarithmic phase cells but was induced at least 30-fold in
      stationary phase. Superoxide, but not peroxide, stress and slow, but not rapid,
      dehydration both caused a slight induction of the DR0975 gene. CONCLUSION:
      Nucleotide substrates for nudix hydrolases conform to the structure NDP-X, where
      X can be one of several moieties. Thus, a preference for (d)NDPs themselves is
      most unusual. The lack of preference for 8-OH-dGDP over dGDP as a substrate
      combined with the induction in stationary phase, but not by peroxide or
      superoxide, suggests that the function of DR09075 may be to assist in the
      recycling of nucleotides under the very different metabolic requirements of
      stationary phase. Thus, if DR0975 does contribute to radiation resistance, this
      contribution may be indirect.

PMID- 15147581
TI  - Sulindac derivatives inhibit cell growth and induce apoptosis in primary cells
      from malignant peripheral nerve sheath tumors of NF1-patients.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms
      leading to death in most cases. Patients with Neurofibromatosis type 1 have an
      increased risk of developing this malignancy. The metabolites of the inactive
      prodrug Sulindac, Sulindac Sulfide and Sulindac Sulfone (Exisulind) are new
      chemopreventive agents that show promising results in the treatment of different
      cancer types. In this study we examined the antineoplastic effect of these
      compounds on primary cells derived from two MPNSTs of Neurofibromatosis type 1
      patients. RESULTS: Exisulind and Sulindac Sulfide showed a dramatic time- and
      dose-dependent growth inhibitory effect with IC50-values of 120 microM and 63
      microM, respectively. The decrease in viability of the tested cells correlated
      with induction of apoptosis. Treatment with 500 microM Exisulind and 125 microM
      Sulindac Sulfide for a period of 2 days increased the rate of apoptosis 21-27
      fold compared to untreated cells. Reduced expression of RAS-GTP and
      phosphorylated ERK1/2 was detected in treated MPNST cells. Moreover, elevated
      levels of phosphorylated SAPK/JNK were found after drug treatment, and low
      activation of cleaved caspase-3 was seen. CONCLUSIONS: Our results suggest that
      this class of compounds may be of therapeutic benefit for Neurofibromatosis type
      1 patients with MPNST.

PMID- 15147582
TI  - Differential expression of E-cadherin, N-cadherin and beta-catenin in proximal
      and distal segments of the rat nephron.
AB  - BACKGROUND: The classical cadherins such as E- and N-cadherin are Ca2+-dependent
      cell adhesion molecules that play important roles in the development and
      maintenance of renal epithelial polarity. Recent studies have shown that a
      variety of cadherins are present in the kidney and are differentially expressed
      in various segments of the nephron. However, the interpretation of these findings
      has been complicated by the fact that the various studies focused on different
      panels of cadherins and utilized different species. Moreover, since only a few of
      the previous studies focused on the rat, information regarding the expression and
      localization of renal cadherins in this important species is lacking. In the
      present study, we have employed dual immunofluorescent labeling procedures that
      utilized specific antibodies against either E- or N-cadherin, along with
      antibodies that target markers for specific nephron segments, to characterize the
      patterns of cadherin expression in frozen sections of adult rat kidney. RESULTS:
      The results showed that N-cadherin is the predominant cadherin in the proximal
      tubule, but is essentially absent in other nephron segments. By contrast, E
      cadherin is abundant in the distal tubule, collecting duct and most medullary
      segments, but is present only at very low levels in the proximal tubule.
      Additional results revealed different patterns of N-cadherin labeling along
      various segments of the proximal tubule. The S1 and S2 segments exhibit a fine
      threadlike pattern of labeling at the apical cell surface, whereas the S3 segment
      show intense labeling at the lateral cell-cell contacts. CONCLUSIONS: These
      results indicate that E- and N-cadherin are differentially expressed in the
      proximal and distal tubules of rat kidney and they raise the possibility that
      differences in cadherin expression and localization may contribute to the
      differences in the susceptibility of various nephron segments to renal pathology
      or nephrotoxic injury.

PMID- 15147583
TI  - Test-retest reliability of temporal and spatial gait characteristics measured
      with an instrumented walkway system (GAITRite).
AB  - BACKGROUND: The purpose of this study was to determine the test-retest
      reliability of temporal and spatial gait measurements over a one-week period as
      measured using an instrumented walkway system (GAITRite). METHODS: Subjects were
      tested on two occasions one week apart. Measurements were made at preferred and
      fast walking speeds using the GAITRite system. Measurements tested included
      walking speed, step length, stride length, base of support, step time, stride
      time, swing time, stance time, single and double support times, and toe in-toe
      out angle. RESULTS: Twenty-one healthy subjects participated in this study. The
      group consisted of 12 men and 9 women, with an average age of 34 years (range: 19
      59 years). At preferred walking speed, all gait measurements had ICC's of 0.92
      and higher, except base of support which had an ICC of 0.80. At fast walking
      speed all gait measurements had ICC's above 0.89 except base of support (ICC =
      0.79), CONCLUSIONS: Spatial-temporal gait measurements demonstrate good to
      excellent test-retest reliability over a one-week time span.

PMID- 15147584
TI  - Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and
      exacerbation of splenomegaly in Kenyan school-aged children.
AB  - BACKGROUND: Schistosoma mansoni and Plasmodium falciparum are common infections
      of school aged children in Kenya. They both cause enlargement of the spleen, but
      their relative contribution to the condition of splenomegaly remains unknown in
      areas where both infections are endemic. Here, we have investigated whether
      relatively high exposure to both infections has a clinically measurable effect on
      this condition. METHODS: 96 children aged 6-16 years living along a ten kilometre
      stretch and within 4 km south of a river that is a source of both S. mansoni and
      malaria infections were examined clinically for splenomegaly along the mid
      clavicular line (MCL) and mid axillary line (MAL). The survey was conducted
      outside the malaria transmission season. The consistency of the organ was
      recorded as soft, firm or hard. Mapping of the locations of houses and the course
      of the river was undertaken. Egg counts were mapped at the household level, as
      were IgG3 responses to Plasmodium falciparum schizont antigen (anti-Pfs IgG3), in
      order to identify areas with relatively high exposure to both infections, either
      infection or neither infection. ANOVA was used to test for differences in egg
      counts, IgG3 levels and the magnitude of spleen enlargement between these areas.
      RESULTS: 4 contiguous sectors were identified, one where anti-Pfs IgG3 responses
      and S. mansoni egg counts were both high, one where only anti-Pfs IgG3 responses
      were high, one where only egg counts were high, and one where both anti-Pfs IgG3
      responses and egg counts were low. Spleen MAL and MCL values were significantly
      higher amongst children from the sector with highest IgG3 levels and highest egg
      counts but similar amongst children from elsewhere. Both egg counts and anti-Pfs
      IgG3 responses were significantly higher in children with MAL values > or =4 cm.
      Hardening of spleens was associated with proximity of domicile to the river.
      CONCLUSIONS: Micro-geographical variation in exposure to S. mansoni and malaria
      infections can be exploited to investigate the chronic impact of these two
      infections. These results provide firm evidence that relatively high exposure to
      both infections exacerbates splenomegaly even outside the malaria transmission
      season. Major implications include assessing the burden of infection in school
      age-children.

PMID- 15147585
TI  - Topical NSAIDs for acute pain: a meta-analysis.
AB  - BACKGROUND: A previous systematic review reported that topical NSAIDs were
      effective in relieving pain in acute conditions like sprains and strains, with
      differences between individual drugs for efficacy. More trials, a better
      understanding of trial quality and bias, and a reclassification of certain drugs
      necessitate a new review. METHODS: Studies were identified by searching
      electronic databases and writing to manufacturers. We selected randomised double
      blind trials comparing topical NSAID with either placebo or another active
      treatment in adults with acute pain, and extracted dichotomous information
      approximating to a 50% reduction in pain at one week, together with details of
      adverse events and withdrawals. Relative benefit and number-needed-to-treat
      (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with
      sensitivity analyses where appropriate to investigate differences between
      individual drugs and aspects of trial design. RESULTS: Twenty-six double blind
      placebo controlled trials had information from 2,853 patients for evaluation of
      efficacy. Topical NSAID was significantly better than placebo in 19 of the 26
      trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to
      1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo
      for the outcome of half pain relief at seven days. Results were not affected by
      outcome reported, or condition treated, but smaller trials yielded a larger
      estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed
      that ketoprofen was significantly better than all other topical NSAIDs, while
      indomethacin was barely distinguished from placebo. Three trials, with 433
      patients, compared topical with oral NSAID (two trials compared the same drug,
      one compared different drugs) and found no difference in efficacy. Local adverse
      events, systemic adverse events, or withdrawals due to an adverse event were
      rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical
      NSAIDs were effective and safe in treating acute painful conditions for one week.

PMID- 15147586
TI  - The effect of a concurrent cognitive task on cortical potentials evoked by
      unpredictable balance perturbations.
AB  - BACKGROUND: Although previous studies suggest that postural control requires
      attention and other cognitive resources, the central mechanisms responsible for
      this relationship remain unclear. To address this issue, we examined the effects
      of altered attention on cortical activity and postural responses following
      mechanical perturbations to upright stance. We hypothesized that cortical
      activity would be attenuated but not delayed when mechanical perturbations were
      applied during a concurrent performance of a cognitive task (i.e. when attention
      was directed away from the perturbation). We also hypothesized that these
      cortical changes would be accompanied by alterations in the postural response, as
      evidenced by increases in the magnitude of anteroposterior (AP) centre of
      pressure (COP) peak displacements and tibialis anterior (TA) muscle activity.
      Healthy young adults (n = 7) were instructed to continuously track (cognitive
      task) or not track (control task) a randomly moving visual target using a hand
      held joystick. During each of these conditions, unpredictable translations of a
      moving floor evoked cortical and postural responses. Scalp-recorded cortical
      activity, COP, and TA electromyographic (EMG) measures were collected. RESULTS:
      Results revealed a significant decrease in the magnitude of early cortical
      activity (the N1 response, the first negative peak after perturbation onset)
      during the tracking task compared to the control condition. More pronounced AP
      COP peak displacements and EMG magnitudes were also observed for the tracking
      task and were possibly related to changes in the N1 response. CONCLUSION: Based
      on previous notions that the N1 response represents sensory processing of the
      balance disturbance, we suggest that the attenuation of the N1 response is an
      important central mechanism that may provide insight into the relationship
      between attention and postural control.

PMID- 15147587
TI  - Multi-pathogens sequence containing plasmids as positive controls for universal
      detection of potential agents of bioterrorism.
AB  - BACKGROUND: The limited circulation of many of the agents that are likely to be
      used in a bioterrorism attack precludes the ready availability of positive
      controls. This means that only specialized laboratories can screen for the
      presence of these agents by nucleic amplification assays. Calibrated controls are
      also necessary for quantitative measurements. Primers and probes to be used in
      both conventional and real-time PCR assays were designed for the detection of
      agents likely to be used by a bioterrorist. Three plasmids, each of which
      contains 4 to 6 specific sequences from agents on the CDC Category A and B list
      (excluding RNA viruses) were constructed. Two plasmids incorporate the sequences
      of Category A and B agents, respectively. The third plasmid incorporates
      sequences from Variola major and organisms that cause rash-like illnesses that
      may be clinically confused with smallpox. An "exogenic sequence", introducing a
      NotI restriction site was incorporated in the native sequences of the
      bioterrorism agents inserted in plasmids. The designed molecular system for
      detection of bioterrorism agents was tested on each of these agents (except
      Monkeypox virus, Smallpox virus and 2 Burkholderia species for which no native
      DNA was available) and a collection of 50 isolates of C. burnetii using
      constructed plasmids as positive controls. RESULTS: Designed primers and probes
      allowed molecular detection, in either single or multiplex assays, of agent
      specific targets with analytical sensitivities of between 1 and 100 DNA copies.
      The plasmids could be used as positive controls. False-positive results due to
      contamination by the positive control were easily detected by sequencing and
      eliminated by digestion with NotI. CONCLUSION: Plasmid A and B can be used as
      positive controls in molecular assays for the detection of bioterrorism agents in
      clinical specimens or environmental samples. Plasmid C can be used as a positive
      control in differentiation of vesicular rashes. It is also possible to avoid or
      to ensure immediate detection of false positive results due to contamination by
      positive controls using these plasmids. These plasmids and the corresponding
      primers and probes are immediately available for all clinical microbiology
      laboratories provided they have molecular amplification equipment.

PMID- 15147588
TI  - A link of Ca2+ to cAMP oscillations in Dictyostelium: the calmodulin antagonist W
      7 potentiates cAMP relay and transiently inhibits the acidic Ca2+-store.
AB  - BACKGROUND: During early differentiation of Dictyostelium the attractant cAMP is
      released periodically to induce aggregation of the cells. Here we pursue the
      question whether pulsatile cAMP signaling is coupled to a basic Ca2+-oscillation.
      RESULTS: We found that the calmodulin antagonist W-7 transiently enhanced cAMP
      spikes. We show that W-7 acts on an acidic Ca2+-store: it abolished ATP-dependent
      vesicular acidification, inhibited V-type H+ATPase activity more potently than
      the weaker antagonist W-5 and caused vesicular Ca2+-leakage. Concanamycin A, an
      inhibitor of the V-type H+-pump, blocked the Ca2+-leakage elicited by W-7 as well
      as cAMP-oscillations in the presence of W-7. Concanamycin A caused an increase of
      the cytosolic Ca2+-concentration whereas W-7 did not. In case of the latter, Ca2+
      was secreted by the cells. In accord with our hypothesis that the link from Ca2+
      to cAMP synthesis is mediated by a Ca2+-dependent phospholipase C we found that W
      7 was not active in the phospholipase C knockout mutant. CONCLUSION: We conclude
      that the potentiation of cAMP relay by W-7 is due to a transient inhibition of
      the acidic Ca2+-store. The inhibition of the proton pump by W-7 causes a leakage
      of Ca2+ that indirectly stimulates adenylyl cyclase activity via phospholipase C.

PMID- 15147589
TI  - Psychosocial outcome of TBI in children with unilateral frontal lesions.
AB  - To evaluate effects of unilateral frontal lesions on psychosocial and global
      outcome of traumatic brain injury (TBI) in children, Study 1 compared matched
      groups of 22 school aged children who had sustained TBI either with or without
      unilateral frontal lesions. Study 2 evaluated effects of unilateral extrafrontal
      lesions in 18 TBI patients as compared with 18 nonlesional TBI patients.
      Communication, Daily Living, and Socialization domains and the Maladaptive
      Behavior Scale of the Vineland Adaptive Behavior Scales (VABS) were used to
      assess psychosocial outcome, and the Glasgow Outcome Scale (GOS) measured global
      outcome. All patients underwent magnetic resonance imaging at least 3 months post
      injury. Children with frontal lesions had worse scores on the Daily Living and
      Socialization domains and a higher frequency of maladaptive behavior than those
      without frontal lesions, but there was no difference in cognitive function.
      Disability was twice as common in the frontal lesion group relative to children
      without frontal lesions. Volume of frontal lesion was related to the
      Socialization domain. Side of lesion had no effect, nor did presence of an
      extrafrontal lesion (Study 2). Unilateral frontal lesions adversely affect late
      psychosocial outcome of TBI in children.

PMID- 15147590
TI  - The impact of HIV-associated neuropsychological impairment on everyday
      functioning.
AB  - HIV-1 infection can be associated with neuropsychological (NP) deficits ranging
      from subtle to severe. The purpose of this study was to evaluate the functional,
      or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV
      infected participants. All participants received comprehensive NP, neuromedical,
      and standardized functional evaluations that included laboratory measures of
      shopping, cooking, financial management, medication management and vocational
      abilities. Compared to NP-normal participants, those with NP impairment performed
      significantly worse on all laboratory measures of everyday functioning.
      Multivariate analyses revealed that the NP ability domains of
      Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal
      abilities most strongly and consistently predicted failures on the functional
      battery. Both NP impairment and impairment on the functional battery were
      significantly associated with subjective experiences of cognitive difficulties,
      as well as unemployment and increased dependence in activities of daily living;
      multivariate prediction models that also considered depressed mood and biological
      measures of disease progression revealed that impairment on the functional
      battery and depression were the only unique predictors of all three indicators of
      "real-world" functioning. The current results add to growing evidence concerning
      the clinical significance of HIV-associated NP impairment. Objective, laboratory
      based functional measures, such as those used here, may compliment NP testing in
      future studies directed at understanding the impact on life quality of central
      nervous system disorders and their treatments. Finally, there is a need for
      additional research investigating the apparently independent effect of depression
      on level of everyday functioning in HIV infected persons.

PMID- 15147591
TI  - Assessment of time perception: the effect of aging.
AB  - Studies concerning time perception lack a validated assessment tool and a
      consensual "gold-standard" measure. Moreover, the present evidence suggests
      modification of timing with aging. This study aimed to develop and validate a
      neuropsychological tool to measure time perception and to study temporal
      perception with aging. Eighty-six healthy participants, aged 15-90 years old,
      were asked to verbally estimate and produce empty intervals signaled by auditory
      beeps, of 7-, 32-, and 58-s duration. Two tests were used as "gold-standards":
      estimation of the duration of time necessary to draw a clock ("clock time") and
      estimation of the duration of neuropsychological evaluation ("global time").
      Results showed a correlation between estimation and production (p < .01) and a
      correlation between estimation or production and "global time" (p < .01). The
      correlation between either estimation or production and age (p < .01), suggested
      a faster "internal-clock" in the older participants. However, this finding lost
      significance when controlled for literacy. The results suggest that these tests
      are potentially a useful tool to measure subjective perception of time. They also
      corroborate the hypothesis of a change in subjective time perception with aging.
      It was not possible to conclude if this effect was a specific result of aging or
      biased by the interference of literacy.

PMID- 15147592
TI  - Everyday functioning in relation to cognitive functioning and neuroimaging in
      community-dwelling Hispanic and non-Hispanic older adults.
AB  - The purpose of this study was to examine how a specific informant-based measure
      of everyday functioning, the Informant Questionnaire on Cognitive Decline in the
      Elderly (IQCODE; Jorm & Korten, 1988) relates to cognition and structural
      neuroimaging in a large multicultural, multilingual sample of Caucasians and
      Hispanics. Cognitive variables included selected subtests from the Spanish and
      English Neuropsychological Assessment Scales (SENAS; Mungas et al., 2000): Verbal
      Memory, Object Naming, Verbal Attention Span, Verbal Conceptual Thinking, and
      Pattern Recognition. The association between the IQCODE and selected neuroimaging
      variables, hippocampal volume and white matter hyperintensity, was evaluated in a
      subsample of English- and Spanish-speaking Hispanic individuals. The cognitive
      variables showed strong bivariate relationships with the IQCODE, although only
      Verbal Memory and Object Naming independently predicted level of functional
      ability. Verbal Memory was the strongest predictor of functional status,
      accounting for 23% of the variance in the IQCODE. White matter hyperintensity was
      also independently related to the IQCODE, accounting for 18% of the variance.
      Hippocampal volume was related to the IQCODE in a simple bivariate analysis, but
      was not an independent predictor of reported functional status after controlling
      for age. The relationships between cognitive variables and functional status, as
      well as between the imaging variables and the IQCODE, did not differ across
      language-ethnic groups.

PMID- 15147593
TI  - Effects of verbal labeling on memory for hand movements.
AB  - This study examined whether a secondary verbal shadowing task influences recall
      for hand movements. Descriptive verbal labels associated with hand postures
      (e.g., "fist", "palm") were presented auditorily, concurrent with video
      presentation of hand postures, and the participant was instructed to shadow the
      words aloud. In the congruent verbal labels condition, the words were matched
      with the hand postures shown, and in the incongruent condition, the labels and
      hand postures were unmatched. In Experiment 1 (N = 18), a computerized version of
      the Kaufman Hand Movements Test (KHMT), which involves three distinct hand
      postures, was performed under congruent and incongruent labels conditions, and
      baseline. For Experiment 2 (N = 18), the same format was applied to a hand
      movement span task, similar to the KHMT, but based on seven distinct hand
      postures. For both experiments, shadowing congruent labels enhanced serial
      recall, whereas shadowing incongruent labels reduced recall when compared to
      baseline. Thus memory for hand movements was affected by the content of the
      secondary verbal task, consistent with participants spontaneously using a verbal
      recoding and rehearsal strategy to support this form of memory, a strategy
      enhanced through the provision of appropriate labels.

PMID- 15147594
TI  - Context-specific memory and apolipoprotein E (ApoE) epsilon 4: cognitive evidence
      from the NIMH prospective study of risk for Alzheimer's disease.
AB  - The aim of the study was to determine whether the epsilon 4 allele of the
      apolipoprotein E (ApoE) gene was associated primarily with context-specific
      memory among individuals at genetic risk for developing Alzheimer's disease. The
      effect of ApoE status on comprehensive neuropsychological results was examined in
      176 healthy adults during baseline cognitive testing in the NIMH Prospective
      Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH
      Prospective BIOCARD Study). The presence of the epsilon 4 allele was associated
      with significantly lower total scores on the Logical Memory II subtest of the
      Wechsler Memory Scale-Revised and percent of information retained after delay.
      Further analysis indicated the prose recall and retention effect was partially
      explained by a small subgroup of epsilon 4 homozygotes, suggesting a gradually
      progressive process that may be presaged with specific cognitive measures. The
      current results may represent an epsilon 4-associated breakdown between gist
      related information and context-bound veridical recall. This relative
      disconnection may be understood in light of putative epsilon 4-related
      preclinical accumulation of Alzheimer pathology (tangles and plaques) in the
      entorhinal cortex (EC) and among frontal networks, as well as the possibility of
      less-efficient compensatory strategies.

PMID- 15147595
TI  - Correlates of memory function in community-dwelling elderly: the importance of
      white matter hyperintensities.
AB  - We sought to identify magnetic resonance- (MR)-imaged structures associated with
      declarative memory in a community-dwelling sample of elderly Mexican-American
      individuals with a spectrum of cognitive decline. Measured structures were the
      hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining
      temporal lobes, as well as severity of white matter signal hyperintensities
      (WMH). Participants were an imaged subsample from the Sacramento Area Latino
      Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory
      impaired (MI), cognitively impaired non-demented (CIND), or demented. We show
      that WMH was the strongest structural predictor for performance on a delayed free
      recall task (episodic memory) in the entire sample. The association of WMH with
      delayed recall was most prominent in elderly normals and mildly cognitively
      impaired individuals with no dementia or impairment of daily function. However,
      the left HC was associated with verbal delayed recall only in people with
      dementia. The right HC volume predicted nonverbal semantic-memory performance. We
      conclude that WMH are an important pathological substrate that affects certain
      memory functions in normal individuals and those with mild memory loss and
      discuss how tasks associated with WMH may rely upon frontal lobe function.

PMID- 15147596
TI  - Similar patterns of cognitive deficits in the preclinical phases of vascular
      dementia and Alzheimer's disease.
AB  - We investigated whether (1) cognitive deficits are present among persons who will
      be diagnosed with vascular dementia (VaD) 3 years later, and (2) the pattern of
      such deficits is similar to that observed in preclinical Alzheimer's disease
      (AD). The VaD diagnosis was a diagnosis of post-stroke dementia. Population-based
      samples of 15 incident VaD cases, 43 incident AD cases, and 149 normal controls
      were compared on tests of episodic and short-term memory, verbal fluency, and
      visuospatial skill. Both dementia groups showed preclinical impairment relative
      controls on tasks assessing episodic memory 3 years before diagnosis, and there
      were no differences between these groups on any cognitive measure. The existence
      of a preclinical phase in the present VaD cases suggests that circulatory
      disturbance may affect cognitive performance before the occurrence of stroke that
      leads to clinical VaD. These results extend previous findings of similar patterns
      of cognitive deficits in the early clinical phases of AD and VaD to the
      preclinical phases of these diseases.

PMID- 15147597
TI  - The d2 Test of attention: construct validity and extensions in scoring
      techniques.
AB  - The internal consistency and convergent and discriminant validity of the d2 Test,
      a cancellation test of attention and concentration, was examined in a sample of
      364 U.S. adults. Test-taking strategy, new process scores for assessing
      performance constancy, and relations to gender and education were explored.
      Results suggested that the d2 Test is an internally consistent and valid measure
      of visual scanning accuracy and speed. Overall performance scores were related to
      a proxy measure of test-taking strategy in the expected direction, and new
      acceleration and deterioration measures exhibited convergent validity. Suggested
      directions for future research include discrimination of attentional processes
      that support immediate and sustained visual scanning accuracy and speed, further
      examination of the impact of test-taking strategies on overall performance
      measures, and additional construct validity examinations for the new process
      measures.

PMID- 15147598
TI  - Cancellation test performance in African American, Hispanic, and White elderly.
AB  - Shape and letter cancellation test performance was investigated among large
      samples of African American, Hispanic, and White non-demented elders. Ethnic
      minority elders took significantly longer to complete both tasks compared to
      Whites. An index of task efficiency, which simultaneously measures time and
      accuracy, suggested that slower time by minority elders was not related to a
      measurable effort to achieve greater accuracy. The frequency of commission errors
      was greater in our sample than in previous reports, especially among ethnic
      minority elders. Although significant differences were observed between the
      ethnic groups when matched for years of education, equating for literacy level
      eliminated all performance differences between African Americans and Whites on
      both cancellation tasks.

PMID- 15147599
TI  - Short- and long-term social outcomes following pediatric traumatic brain injury.
AB  - The social outcomes of pediatric traumatic brain injury (TBI) were examined in a
      prospective, longitudinal study that included 53 children with severe TBI, 56
      with moderate TBI, and 80 with orthopedic injuries, recruited between 6 and 12
      years of age. Child and family functioning were assessed at baseline, at 6- and
      12-month follow-ups, and at an extended follow-up a mean of 4 years post injury.
      Growth curve analyses revealed that pediatric TBI yields negative social outcomes
      that are exacerbated by family environments characterized by lower socioeconomic
      status, fewer family resources, and poorer family functioning. After controlling
      for group membership, age, race, socioeconomic status, and IQ, path analyses
      indicated that long-term social outcomes were accounted for in part by specific
      neurocognitive skills, including executive functions and pragmatic language, and
      by social problem-solving. Deficits in these domains among children with TBI are
      likely to reflect damage to a network of brain regions that have been implicated
      in social cognition.

PMID- 15147600
TI  - Dissociation of remote and anterograde memory impairment and neural correlates in
      alcoholic Korsakoff syndrome.
AB  - Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment
      together with characteristic profound anterograde memory deficits. Despite
      previous studies of memory processes in KS, questions remain regarding the nature
      and severity of these impairments and identification of brain systems that
      underlie these different memory impairments. This study examined remote and
      anterograde memory function in 5 KS patients in comparison with 8 patients with
      Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition,
      relationships between memory performance and regional brain volumes were examined
      in the KS group. Overall, the KS group showed severe impairment on both remote
      and anterograde memory measures, performing at the level of the AD group on most
      measures. Differences were observed on the pattern of temporal gradient for
      verbal recognition, with KS exhibiting a more steeply graded rate of decline over
      the most recent period examined. Severity of the remote memory deficit in KS was
      not associated with severity of anterograde memory deficit. Examination of brain
      structure-function relationships in the KS subjects revealed that photo naming of
      remote historical information was related to posterior cortical white matter
      volumes but not hippocampal volumes; sequencing was related to prefrontal but not
      hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal
      visual material showed a relationship to hippocampal but not regional cortical
      white matter volumes. This set of dissociations, which parallels that observed in
      our earlier study of AD, is now documented in KS and provides further evidence
      that these separate cortical and limbic brain systems are principal neural
      substrates of the remote and anterograde memory and sequencing deficits in KS.

PMID- 15147602
TI  - Assessing the elusive cognitive deficits associated with ventromedial prefrontal
      damage: a case of a modern-day Phineas Gage.
AB  - Cognitive deficits following ventromedial prefrontal damage (VM-PFD) have been
      elusive, with most studies reporting primarily emotional and behavioral changes.
      The present case illustrates the utility of a process approach to assessing
      cognitive deficits following VM-PFD. At age 26, C.D. acquired bilateral VM-PFD,
      more so in the left frontal region, following a penetrating head injury. Despite
      exemplary premorbid academic and military performances, his subsequent history
      suggests dramatic occupational and social changes, reminiscent of Phineas Gage.
      In fact, lesion analysis revealed similar structural damage to that estimated of
      Gage. C.D.'s scores on the vast majority of neuropsychological measures were
      average to superior (e.g., Verbal IQ = 119). However, on several new process
      measures, particularly those that quantify error rates on multilevel executive
      function and memory tasks, C.D. exhibited marked impairments. From his pattern of
      deficits, C.D. appeared to sacrifice accuracy for speed and to adopt liberal
      response strategies, implicating problems with cognitive inflexibility,
      impulsivity, and disinhibition. The current findings suggest that VM-PFD may be
      associated with a wider spectrum of cognitive deficits than previously
      characterized.

PMID- 15147601
TI  - Cerebral volume loss, cognitive deficit and neuropsychological performance:
      comparative measures of brain atrophy: I. Dementia.
AB  - There are several magnetic resonance (MR) imaging methods to measure brain volume
      and cerebral atrophy; however, the best measure for examining potential
      relationships between such measures and neuropsychological performance has not
      been established. Relationships between seven measures of MR derived brain volume
      or indices of atrophy and neuropsychological performance in the elderly subjects
      of the population-based Cache County, Utah Study of Aging and Memory (n = 195)
      were evaluated. The seven MR measures included uncorrected total brain volume
      (TBV), TBV corrected by total intracranial volume (TICV), TBV corrected by the
      ratio of the individuals TICV by group TICV (TBVC), a ventricle-to-brain ratio
      (VBR), total ventricular volume (TVV), TVV corrected by TICV, and a measure of
      parenchymal volume loss. The cases from the Cache County Study were comprised of
      elderly individuals classified into one of four subject groups based on a
      consensus diagnostic process, independent of quantitative MR imaging findings.
      The groups included subjects with Alzheimer's disease (AD, n = 85), no dementia
      but mild/ambiguous (M/A) deficits (n = 30), a group of subjects with non-AD
      dementia or neuropsychiatric disorder including vascular dementia (n = 60), and
      control subjects (n = 20). Neuropsychological performance was based on the Mini
      Mental Status Exam (MMSE) and an expanded neuropsychological test battery
      (consortium to establish a registry for Alzheimer's disease (CERAD). The results
      demonstrated that the various quantitative MR measures were highly interrelated
      and no single measure was statistically superior. However, TBVC, TBV/TICV and VBR
      consistently exhibited the more robust relationships with neuropsychological
      performance. These results suggest that a single corrected brain volume measure
      or index is sufficient in studies examining global MR indicators of cerebral
      atrophy in relation to cognitive function and recommends use of either TBVC,
      TBV/TICV, or VBR.

PMID- 15147608
TI  - Critical evaluation of p53 as a prognostic marker in ovarian cancer.
AB  - The tumour suppressor gene encoding p53 has been shown from experimental studies
      to have a crucial role in how cells respond to DNA damage. p53 has important
      functions in apoptosis, cell-cycle arrest and DNA repair, largely mediated by its
      activity on gene transcription. However, despite this wealth of in vitro data,
      its role in how tumours respond to DNA damage induced by chemotherapeutic drugs
      remains controversial. In this review, we highlight some of the problems
      surrounding design and analysis of studies of p53 as a prognostic marker of
      clinical outcome, using ovarian cancer as an example. We aim to build on the
      knowledge of the published literature in ovarian cancer to identify criteria for
      clinical studies that should give a more definitive estimate of the role of p53
      in clinical drug resistance. A search of three public databases using keywords
      combined with Boolean operators identified 64 clinical publications investigating
      the relationship of p53 to clinical outcome following chemotherapy in ovarian
      cancer. Although 43% of 215 published analyses from the 64 papers reported a
      significant correlation between p53 status and a clinical endpoint relevant to
      chemoresistance, only six analyses fulfil minimum criteria and none of these
      finds a statistically significant correlation of p53 with chemotherapy-resistance
      endpoints. The results from published clinical studies suggest a more complex
      role of p53 mutation in the mechanism of resistance in ovarian cancer than is
      suggested by in vitro studies.

PMID- 15147609
TI  - A rapid and systematic review and economic evaluation of the clinical and cost
      effectiveness of newer drugs for treatment of mania associated with bipolar
      affective disorder.
AB  - OBJECTIVES: To evaluate the clinical and cost-effectiveness of quetiapine,
      olanzapine and valproate semisodium in the treatment of mania associated with
      bipolar disorder. DATA SOURCES: Electronic databases; industry submissions made
      to the National Institute for Clinical Excellence. REVIEW METHODS: Randomised
      trials and economic evaluations that evaluated the effectiveness of quetiapine,
      olanzapine or valproate semisodium in the treatment of mania associated with
      bipolar disorder were selected for inclusion. Data were extracted by one reviewer
      into a Microsoft Access database and checked for quality and accuracy by a
      second. The quality of the cost-effectiveness studies was assessed using a
      checklist updated from that developed by Drummond and colleagues. Relative risk
      and mean difference data were presented as Forest plots but only pooled where
      this made sense clinically and statistically. Studies were grouped by drug and,
      within each drug, by comparator used. Chi-squared tests of heterogeneity were
      performed for the outcomes if pooling was indicated. A probabilistic model was
      developed to estimate costs from the perspective of the NHS, and health outcomes
      in terms of response rate, based on an improvement of at least 50% in a patient's
      baseline manic symptoms derived from an interview-based mania assessment scale.
      The model evaluated the cost-effectiveness of the alternative drugs when used as
      part of treatment for the acute manic episode only. RESULTS: Eighteen randomised
      trials met the inclusion criteria. Aspects of three of the quetiapine studies
      were commercial-in-confidence. The quality of the included trials was limited and
      overall, key methodological criteria were not met in most trials. Quetiapine,
      olanzapine and valproate semisodium appear superior to placebo in reducing manic
      symptoms, but may cause side-effects. There appears to be little difference
      between these treatments and lithium in terms of effectiveness, but quetiapine is
      associated with somnolence and weight gain, whereas lithium is associated with
      tremor. Olanzapine as adjunct therapy to mood stabilisers may be more effective
      than placebo in reducing mania and improving global health, but it is associated
      with more dry mouth, somnolence, weight gain, increased appetite, tremor and
      speech disorder. There was little difference between these treatments and
      haloperidol in reducing mania, but haloperidol was associated with more
      extrapyramidal side-effects and negative implications for health-related quality
      of life. Intramuscular olanzapine and lorazepam were equally effective and safe
      in one very short (24 hour) trial. Valproate semisodium and carbamazepine were
      equally effective and safe in one small trial in children. Olanzapine may be more
      effective than valproate semisodium in reducing mania, but was associated with
      more dry mouth, increased appetite, oedema, somnolence, speech disorder,
      Parkinson-like symptoms and weight gain. Valproate semisodium was associated with
      more nausea than olanzapine. The results from the base-case analysis demonstrate
      that choice of optimal strategy is dependent on the maximum that the health
      service is prepared to pay per additional responder. For a figure of less than
      7179 British pounds per additional responder, haloperidol is the optimal
      decision; for a spend in excess of this, it would be olanzapine. Under the most
      favourable scenario in relation to the costs of responders and non-responders
      beyond the 3-week period considered in the base-case analysis, the incremental
      cost-effectiveness ratio of olanzapine is reduced to 1236 British pounds.
      CONCLUSIONS: In comparison with placebo, quetiapine, olanzapine and valproate
      semisodium appear superior in reducing manic symptoms, but all drugs are
      associated with adverse events. In comparison with lithium, no significant
      differences were found between the three drugs in terms of effectiveness, and all
      were associated with adverse events. Several limitations of the cost
      effectiveness analysis exist, which inevitably means that the results should be
      treated with some caution. There remains a need for well-conducted, randomised,
      double-blind head-to-head comparisons of drugs used in the treatment of mania
      associated with bipolar disorder and their cost-effectiveness. Participant
      demographic, diagnostic characteristics, the treatment of mania in children, the
      use of adjunctive therapy and long-term safety issues in the elderly population,
      and acute and long-term treatment are also subjects for further study.

PMID- 15147610
TI  - Systematic review of the long-term effects and economic consequences of
      treatments for obesity and implications for health improvement.
AB  - OBJECTIVES: To undertake a systematic review of the long-term effects of obesity
      treatments on body weight, risk factors for disease, and disease. METHODS: The
      study encompassed three systematic reviews that examined different aspects of
      obesity treatments. (1) A systematic review of obesity treatments in adults where
      the methods of the Cochrane Collaboration were applied and randomised controlled
      trials (RCTs) with a follow-up of at least 1 year were evaluated. (2) A
      systematic epidemiological review, where studies were sought on long-term effects
      of weight loss on morbidity and/or mortality, and examined through
      epidemiological modelling. (3) A systematic economic review that sought reports
      with both costs and outcomes of treatment, including recent reports that assessed
      the cost-effectiveness of pharmaceutical and surgical interventions. A Markov
      model was also adopted to examine the cost-effectiveness of a low-fat diet and
      exercise intervention in adults with obesity and impaired glucose tolerance.
      RESULTS: The addition of the drugs orlistat or sibutramine was associated with
      weight loss and generally improved risk factors, apart from diastolic blood
      pressure for sibutramine. Metformin was associated with decreased mortality after
      10 years in obese people with type 2 diabetes. Low-fat diets were associated with
      continuing weight loss for 3 years and improvements in risk factors, as well as
      prevention of type 2 diabetes and improved control of hypertension. Insufficient
      evidence was available to demonstrate the benefits of low calorie or very low
      calorie diets. The addition of an exercise or behaviour programme to diet was
      associated with improved weight loss and risk factors for at least 1 year.
      Studies combining low-fat diets, exercise and behaviour therapy suggested
      improved hypertension and cardiovascular disease. Family therapy was associated
      with improved weight loss for 2 years compared to individual therapy. There was
      insufficient evidence to conclude that individual therapy was more beneficial
      than group therapy. Weight lost more quickly (within 1 year), from the
      epidemiology review, may be more beneficial with respect to the risk of
      mortality. The effects of intentional weight loss need further investigation.
      Weight loss from surgical and non-surgical interventions for people suffering
      from obesity was associated with decreased risk of development of diabetes, and a
      reduction in low-density lipoprotein cholesterol, total cholesterol and blood
      pressure, in the long term. Targeting high-risk individuals with drugs or surgery
      was likely to result in a cost per additional life-year or quality-adjusted life
      year (QALY) of no more than 13,000 British pounds. There was also suggestive
      evidence of cost saving from treatment of people with type 2 diabetes with
      metformin. Targeting surgery on people with severe obesity and impaired glucose
      tolerance was likely to be more cost-effective at 2329 British pounds per
      additional life-year. Economic modelling over 6 years for diet and exercise for
      people with impaired glucose tolerance was associated with a high initial cost
      per additional QALY, but by the sixth year the cost per QALY was 13,389 British
      pounds. Results did not include cost savings from diseases other than diabetes,
      and therefore may be conservative. CONCLUSIONS: The drugs orlistat and
      sibutramine appear beneficial for the treatment of adults with obesity, and
      metformin for obese patients with type 2 diabetes. Exercise and/or behaviour
      therapy appear to improve weight loss when added to diet. Low-fat diets with
      exercise, or with exercise and behaviour therapy are associated with the
      prevention of type 2 diabetes and hypertension. Long-term weight loss in
      epidemiological studies was associated with reduced risk of type 2 diabetes, and
      may be beneficial for cardiovascular disease. Low-fat diets and exercise
      interventions in individuals at risk of obesity-related illness are of comparable
      cost to drug treatments. Long-term pragmatic RCTs of obesity treatments in
      populations with obesity-related illness or at high risk of developing such
      illness are needed (to include an evaluation of risk factors, morbidity, quality
      of life and economic evaluations). Drug trials that include dietary advice, plus
      exercise and/or behaviour therapy are also needed. Research exploring effective
      types of exercise, diet or behaviour and also interventions to prevent obesity in
      adults is required.

PMID- 15147611
TI  - Liquid-based cytology in cervical screening: an updated rapid and systematic
      review and economic analysis.
AB  - OBJECTIVES: To update an earlier published report reviewing the effectiveness and
      cost-effectiveness of liquid-based cytology (LBC). DATA SOURCES: Electronic
      bibliographic databases, relevant articles, sponsor submissions and various
      health services research-related resources. REVIEW METHODS: The selected data
      were reviewed and assessed with respect to the quality of the evidence. Pooled
      estimates of the parameters of interest were derived from the original and the
      updated studies. Meta-analyses were undertaken where appropriate. The
      mathematical model developed for the original rapid review of LBC was adapted to
      synthesise the updated data to estimate costs, survival and quality-adjusted
      survival of patients tested using LBC and using Papanicolaou (Pap) smear testing.
      Cost data from published sources were incorporated into the above model to allow
      economic, as well as clinical, implications of treatment to be assessed. The
      primary incremental cost-effectiveness ratio is the cost per life year gained
      (LYG), although estimates of the cost per quality-adjusted life-year (QALY)
      gained are also presented. A sensitivity analysis was undertaken to identify the
      key parameters that determine the cost-effectiveness of the treatments, with the
      objective of identifying how robust the results of the economic analysis are,
      given the current level of evidence. RESULTS: From the evidence available, it is
      likely that the LBC technique will reduce the number of false-negative test
      results. Modelling analyses undertaken as part of this study indicate that this
      would reduce the incidence of invasive cancer. There is now more evidence to
      support improvements emanating from the use of LBC screening in terms of a
      reduced number of unsatisfactory specimens and a decrease in the time needed to
      obtain the smear samples. The estimated annual gross cost of consumables and
      operating equipment, and other one-off conversion costs associated with
      introducing the new technique, will be between 17 British pounds and 38 British
      pounds million in England and Wales, depending on the LBC system and the
      configuration of the service. Analyses based on models of disease natural
      history, conducted in this study, showed that conventional Pap smear screening
      was extendedly dominated by LBC (LBC was always more cost-effective than
      conventional Pap smear testing over the same screening interval). Comparing LBC
      across alternative screening intervals gave a cost-effectiveness of under 10,000
      British pounds per LYG when screening was undertaken every 3 years. The cost
      effectiveness results were relatively stable under most conditions, although if
      screening outcomes such as borderline results and colposcopy are assumed to
      induce even small amounts of disutility then LBC screening at 5-yearly intervals
      may be the most cost-effective option. CONCLUSIONS: This updated analysis
      provides more certainty with regard to the potential cost-effectiveness of LBC
      compared with conventional Pap smear testing. However, there is uncertainty
      regarding the relative effectiveness (and cost-effectiveness) of the two main LBC
      techniques. Further research in the area of utility assessment may be worthwhile
      and possibly a full cost-effectiveness study of LBC based on a trial of its
      introduction in a low-prevalence population, although the results of the
      modelling analysis provide a robust argument that LBC is a cost-effective
      alternative to conventional cervical cancer screening. A randomised comparison of
      the two main techniques may also be useful.

PMID- 15147612
TI  - Mammography "dose creep": causes and solutions.

PMID- 15147613
TI  - Validation of the CBF, CBV, and MTT values by perfusion MRI in chronic occlusive
      cerebrovascular disease: a comparison with 15O-PET.
AB  - RATIONALE AND OBJECTIVES: To evaluate the reliability of cerebral blood flow
      (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values obtained
      by deconvolution algorithm perfusion-weighted MR imaging (D-PWI), we compared
      these values with those obtained by first-moment algorithm perfusion-weighted MR
      imaging (F-PWI) and 15O-PET. SUBJECTS AND METHODS: Six healthy volunteers and
      eleven patients with chronic occlusive cerebrovascular disease were studied with
      both perfusion-weighted MR imaging and 15O-PET, and region-of-interest analyses
      were performed. Normalization factors for CBF and CBV values obtained by D-PWI
      were determined as the mean values of 15O-PET divided by those of D-PWI in
      healthy volunteers. Then these values were used in analyzing the data of the
      patients. RESULTS: The MTT value obtained by D-PWI was 6.1 +/- 0.5 seconds on the
      non-occluded side, 6.4 +/- 0.7 seconds on the minimally to moderately stenosed
      side, and 6.7 +/- 1.2 seconds on the severely stenosed to occluded side. These
      values were significantly correlated with those obtained by F-PWI (r = 0.83; P <
      .001), and with those obtained by 15O-PET (r = 0.78; P < .05). However, the CBF
      and CBV values obtained by D-PWI did not correlate with those obtained by 15O
      PET. CONCLUSION: MTT values obtained by D-PWI were reliable parameters of
      cerebral hemodynamics, but the CBF and CBV values obtained by D-PWI were not
      always reliable.

PMID- 15147614
TI  - Improved detection of lung cancer arising in diffuse lung diseases on chest
      radiographs using temporal subtraction.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
      usefulness of temporal subtraction for the detection of lung cancer arising in
      pneumoconiosis, idiopathic pulmonary fibrosis, and pulmonary emphysema. MATERIALS
      AND METHODS: Fifteen cases of lung cancer arising in diffuse lung diseases,
      including three cases of pneumoconiosis, six of idiopathic pulmonary fibrosis,
      and six of pulmonary emphysema, were evaluated. Pathologic proof was obtained by
      surgery or transbronchial lung biopsy. The average interval between previous and
      current radiographs was 356 days (range, 31-947 days). All chest radiographs were
      obtained with a computed radiography system, and temporal subtraction images were
      produced by subtracting of a previous image from a current one with a nonlinear
      image-warping technique. The effect of the temporal subtraction image was
      evaluated by observer performance study with receiver operating characteristic
      analysis. RESULTS: The average observer performance with temporal subtraction was
      significantly improved (Az = 0.935) compared with that without temporal
      subtraction (Az = 0.857, P < .0001). CONCLUSION: The temporal subtraction
      technique is useful for the detection of lung cancer arising in pneumoconiosis,
      idiopathic pulmonary fibrosis, and pulmonary emphysema.

PMID- 15147615
TI  - Comparison of MR imaging sequences for liver and head and neck interventions: is
      there a single optimal sequence for all purposes?
AB  - RATIONALE AND OBJECTIVES: To compare the appropriate pulse sequences for
      interventional device guidance during magnetic resonance (MR) imaging at 0.2 T
      and to evaluate the dependence of sequence selection on the anatomic region of
      the procedure. MATERIALS AND METHODS: Using a C-arm 0.2 T system, four
      interventional MR sequences were applied in 23 liver cases and during MR-guided
      neck interventions in 13 patients. The imaging protocol consisted of: multislice
      turbo spin echo (TSE) T2w, sequential-slice fast imaging with steady precession
      (FISP), a time-reversed version of FISP (PSIF), and FISP with balanced gradients
      in all spatial directions (True-FISP) sequences. Vessel conspicuity was rated and
      contrast-to-noise ratio (CNR) was calculated for each sequence and a differential
      receiver operating characteristic was performed. RESULTS: Liver findings were
      detected in 96% using the TSE sequence. PSIF, FISP, and True-FISP imaging showed
      lesions in 91%, 61%, and 65%, respectively. The TSE sequence offered the best
      CNR, followed by PSIF imaging. Differential receiver operating characteristic
      analysis also rated TSE and PSIF to be the superior sequences. Lesions in the
      head and neck were detected in all cases by TSE and FISP, in 92% using True-FISP,
      and in 84% using PSIF. True-FISP offered the best CNR, followed by TSE imaging.
      Vessels appeared bright on FISP and True-FISP imaging and dark on the other
      sequences. CONCLUSION: In interventional MR imaging, no single sequence fits all
      purposes. Image guidance for interventional MR during liver procedures is best
      achieved by PSIF or TSE, whereas biopsies in the head and neck are best performed
      using FISP or True-FISP sequences.

PMID- 15147616
TI  - Statistical assessment of regional time-density measurement of myocardial
      perfusion.
AB  - RATIONALE AND OBJECTIVES: The measurement of time-density relationships of the
      myocardium in studies of magnetic resonance perfusion images is a clinical
      technique used in assessing myocardial perfusion. This article presents a new
      technique, allowing regional time-density measurement and display of myocardial
      perfusion with improved accuracy compared with traditional manual trace
      techniques. Moreover, a method using statistical methods to discriminate relative
      decreased perfusion regions that differ significantly from the normally perfused
      myocardial tissue is introduced. MATERIALS AND METHODS: Human datasets were
      obtained using a 1.5 T Signa Echospeed system (GE Medical Systems, Milwaukee,
      WI). The perfusion sequence was a 2D cardiac-gated fast gradient echo sequence
      with echo train readout, generating an in-plane pixel size of 1.46 mm2. Seven 10
      mm-thick contiguous short axis tomographic slice images were obtained during a
      prolonged single breathhold. Data was collected at 30 time phases per slice image
      level during passage of 20 cc gadolinium contrast injected at a rate of 4-5
      cc/sec into an antecubital vein. RESULTS: Dilution properties can be determined
      and displayed as color-encoded regions superimposed on the myocardial slice
      according to the area of interest. Time-density curves throughout the perfusion
      study can be generated. Moreover, displays of normal and decreased perfusion
      areas can be used as statistically enhanced diagnosis guides. CONCLUSION: This
      measurement, display, and diagnosis technique adds diagnostically important
      information to previous measurement and visualization techniques, providing
      enhanced detection and quantitative evaluation of regional deficits in myocardial
      contractility and perfusion, providing improved reliability and reproducibility
      of clinical diagnoses from MR-perfusion data.

PMID- 15147617
TI  - Computerized detection and classification of cancer on breast ultrasound.
AB  - RATIONALE AND OBJECTIVES: To develop and evaluate a two-stage computerized method
      that first detects suspicious regions on ultrasound images, and subsequently
      distinguishes among different lesion types. MATERIALS AND METHODS: The first
      stage of detecting potential lesions was based on expected lesion shape and
      margin characteristics. After the detection stage, all candidate lesions were
      classified by a Bayesian neural net based on computer-extracted lesion features.
      Two separate tasks were performed and evaluated at the classification stage: the
      first classification task was the distinction between all actual lesions and
      false-positive detections; the second classification task was the distinction
      between actual cancer and all other detected lesion candidates (including false
      positive detections). The neural nets were trained on a database of 400 cases
      (757 images), consisting of complex cysts and benign and malignant lesions, and
      tested on an independent database of 458 cases (1,740 images including 578 normal
      images). RESULTS: In the distinction between all actual lesions and false
      positive detections, Az values of 0.94 and 0.91 were obtained with the training
      and testing data sets, respectively. Sensitivity by patient of 90% at 0.45 false
      positive detections per image was achieved for this detection-plus-classification
      scheme for the testing data set. Distinguishing cancer from all other detections
      (false-positives plus all benign lesions) proved to be more challenging, and Az
      values of 0.87 and 0.81 were obtained during training and testing, respectively.
      Sensitivity by patient of 100% at 0.43 false-positive malignancies per image was
      achieved in the detection and classification of cancerous lesions for the testing
      dataset. CONCLUSION: The results show promising performance of the computerized
      lesion detection and classification method, and indicate the potential of such a
      system for clinical breast ultrasound.

PMID- 15147618
TI  - Factors affecting increasing radiation dose for mammography in North Carolina
      from 1997 through 2001: an analysis of Food and Drug Administration annual
      surveys.
AB  - RATIONALE AND OBJECTIVES: To determine which factors affected the increase in
      average glandular dose recorded at the annual US Food and Drug Administration
      Mammography Quality Standards Act inspections of mammography equipment in North
      Carolina from 1997 to 2001. MATERIALS AND METHODS: Average glandular dose, HVL,
      kVp, ambient light, luminance, equipment age, processing speed, and system speed
      for every mammography unit at all facilities in the state were collected by state
      inspectors. A mixed-effect model was used to assess the average changes of
      glandular dose over time and to identify the factors associated with these
      changes. RESULTS: There was a statistically significant increase in the average
      glandular dose in North Carolina in 1999, 2000, and 2001 when compared with the
      baseline year of 1997. Factors that were statistically significantly linked to
      this effect were changes in kVp, processing speed, and system speed. CONCLUSION:
      Average glandular dose for mammography has recently increased in North Carolina.
      This change is likely caused by changes in screen-film products and processing
      techniques.

PMID- 15147619
TI  - Use of 2D histograms for volume rendering of multidetector CT data: development
      of a graphical user interface.
AB  - RATIONALE AND OBJECTIVES: Direct volume rendering reveals 3D information on
      anatomic structures without preprocessing the data. This increases the interest
      in this technique as a diagnostic tool. A fast and simple method for setting
      transfer functions is crucial for clinical routine work. However, this is still a
      complex task. Present commercial workstations are usually limited to design
      galleries and window/level functionality. MATERIALS AND METHODS: We present a
      graphical user interface for volume rendering of multidetector row CT data that
      permits a much more flexible specification of rendering parameters. A 2D
      histogram of CT density versus gradient magnitude facilitates the understanding
      of the spatial connections of different tissues. The incorporation of gradient
      magnitude into the transfer function domain allows discrimination of features of
      interest that are not distinguishable on CT density alone. Penetration length,
      color, and gradient magnitude are depicted on a stack of 2D slices according to
      the settings of the opacity transfer function and the viewing direction. A
      gallery of thumbnails with presets of transfer functions is interactively adapted
      if the volume is rotated or cropped. RESULTS: This allows for fast evaluation of
      numerous rendering protocols at once. The interface was evaluated with CT data
      covering skeletal trauma, pathologies of the thorax/abdomen, and CT angiography.
      CONCLUSION: We observed that high-quality visualizations could be obtained with
      reasonable interaction times. The 2D histogram and penetration length displays
      provided valuable insight into the dataset that made the specification of
      transfer functions a goal-oriented process.

PMID- 15147621
TI  - Online annotation tool for digital mammography.
AB  - RATIONALE AND OBJECTIVES: To develop a software tool for radiologists to annotate
      mammograms online. MATERIALS AND METHODS: The tool is web-based with a Java
      development environment and composed of a Digital Image and Communication in
      Medicine (DICOM) image viewer, a clinical information collector, and a database.
      The use of the tool with a sample case is demonstrated in this article. RESULTS:
      An online tool for the annotation of digital mammograms for teaching and research
      purposes has been developed. CONCLUSION: This annotation tool can be used to
      provide an annotated-case library on mammography education for residents and
      fellows.

PMID- 15147620
TI  - Hybrid segmentation and virtual bronchoscopy based on CT images.
AB  - RATIONALE AND OBJECTIVES: Introduction of combination of the segmentation tool
      SegoMeTex and the virtual endoscopy system VIVENDI to perform virtual endoscopic
      inspections of the human lung. This virtual bronchoscopy system enables
      visualization of the tracheobronchial tree down to seventh generation.
      Furthermore, the modified virtual system visualizes hidden structures such as
      segmented vascular system or tumors. MATERIALS AND METHODS: The segmentation is
      based on image data acquired by a multislice computed tomography scanner.
      SegoMeTex is used to segment the tracheobronchial tree by a hybrid system with
      minimal user action. Similarly, the complementary pulmonary arterial can be
      segmented, whereas additional structures such as tumors are marked manually. On
      this dataset, subsequently, data structures of the inner surface for virtual
      endoscopy are generated. Finally, the dataset can be explored by a virtual
      bronchoscopy procedure using the VIVENDI system. RESULTS: The segmentation method
      was successfully tested on 22 patients. The hybrid segmentation system identified
      bronchi up to the sixth generation with a sensitivity of more than 58%, and a
      positive predictive value of more than 90%. After the segmentation, the datasets
      are explored interactively (>30 fps on a standard personal computer platform in
      real-time rendering) using the virtual endoscopy software. The exploration
      exposed a high-quality reconstruction, even of small structures throughout the
      dataset. CONCLUSION: Virtual bronchoscopy in combining with a highly sensitive
      segmentation is a valuable tool for the localization and measurement of stenosis
      for resection planning.

PMID- 15147622
TI  - Quantification of angiogenesis by functional computed tomography in a Matrigel
      model in rats.
AB  - RATIONALE AND OBJECTIVES: The aim was to evaluate functional computed tomography
      (fCT) in the quantification of angiogenesis by comparing the tissue perfusion
      parameters measured by CT perfusion (CTP) software with histologic vascular
      parameters in a Matrigel model in rats. It was hypothesized that tissue perfusion
      parameters and histologic vascular parameters are related. MATERIALS AND METHODS:
      In vivo angiogenesis assays were performed using Matrigel supplemented with
      escalating doses (0 ng [control group], 250 ng, and 1,000 ng) of recombinant rat
      vascular endothelial growth factor (VEGF164) subcutaneously injected into the
      backs of Sprague Dawley rats. On day 7, rats with Matrigel plug underwent fCT
      following a bolus injection of iodinated contrast medium. Using CTP software, fCT
      parameters were generated (blood flow [BF], blood volume [BV], mean transit time,
      and permeability-surface area product) and functional maps on the basis of a
      distributed parameter tracer kinetic model, the adiabatic approximation to the
      tissue homogeneity model. The animals were then sacrificed. Matrigel plug was
      sectioned into slices corresponding to the CT scan plane and stained with CD31
      immunohistochemical stain. Histologic vascular parameters, including
      microvascular density (MVD), vessel number (VN), vascular area, and vascular
      perimeter, were measured. CTP and histologic parameters were correlated. RESULTS:
      The Matrigel plugs with the 1,000-ng VEGF group exhibited a higher MVD than the
      250-ng VEGF and control groups (P < .05). VN differed significantly between the
      control versus the 250-ng VEGF groups and 250-ng versus 1,000-ng VEGF groups (P <
      .05), with the highest VN in the 250-ng VEGF group. BF, mean transit time, and
      permeability-surface area product each differed significantly to VEGF levels.
      Changes in BF and BV did not correspond with increases in MVD or VN; however, in
      the 250-ng VEGF group, there was a strong positive correlation (r = 0.9) between
      BV and VN, vascular area, and vascular perimeter, which was not seen in the
      control or 1,000-ng VEGF group. All fCT parameters significantly correlated with
      each other (P < .05), with strong correlations between BF and mean transit time
      (r = -0.7) and between BF and permeability-surface area product (r = 0.7) and a
      weak correlation between BF and BV (r = 0.3). CONCLUSION: These results validate
      the VEGF-induced endothelial cell in a rat Matrigel model. In addition,
      histologic vascular parameter MVD does not correlate with fCT parameters measured
      by CTP software.

PMID- 15147624
TI  - Define a national curriculum for radiology residents and test from it.

PMID- 15147625
TI  - Commentary on curriculum.

PMID- 15147623
TI  - Adding sodium and calcium ions to the contrast medium iodixanol reduced the risk
      of ventricular fibrillation during perfusion of the left coronary artery in pigs:
      effects of electrolytes, viscosity, and chemotoxicity of an isotonic perfusate.
AB  - RATIONAL AND OBJECTIVES: The effects of electrolytes, viscosity, and
      chemotoxicity of a plasma-isotonic iodine contrast medium iodixanol were compared
      with regard to its propensity to cause ventricular fibrillation (VF). MATERIALS
      AND METHODS: The left coronary artery of pigs was perfused with five isotonic
      solutions: iodixanol 320 mg I/mL with 19 mmol/L NaCl + 0.3 mmol/L CaCl2, Iod
      320+Mann (iodixanol 320 mg I/mL + 50 mmol/L mannitol), Mann+Na/Ca (240 mmol/L
      mannitol with 19 mmol/L NaCl + 0.3 mmol/L CaCl2), Mann (275 mmol/L mannitol) and
      Ringer. The first two solutions have at 37 degrees C a viscosity of approximately
      13 mPa x s while the others have a viscosity < 1 mPa x s. In eight pigs, each
      test solution was injected twice into the left coronary artery in random order
      for 10 seconds (injection volume, 20 mL). In 15 pigs, each of the solutions was
      injected in random order for 11-40 seconds through the end-hole of a wedged 5F
      balloon catheter in left coronary artery. Injection rate was 0.5 mL/sec until VF
      occurred. If VF occurred, injection was stopped and the heart was defibrillated.
      If VF did not occur, the perfusion period was 40 seconds. RESULTS: The 10-second
      perfusions caused no VF. The 40-second perfusions with iodixanol 320 mg I/mL with
      19 mmol/L NaCl + 0.3 mmol/L CaCl2 or Ringer caused no VF (0%). Iod 320+Mann
      caused nine VF (60%) after 35 +/- 4 seconds (SEM). Mann+Na/Ca caused 14 VF (93%)
      after 30 +/- 2 seconds. Mann caused 15 VF (100%) after 24 +/- 2 seconds.
      Iodixanol 320 mg I/mL with 19 mmol/L NaCl + 0.3 mmol/L CaCl2 and Ringer caused
      fewer VF than all other solutions (P < .05-.001). Iod 320+Mann caused fewer VF
      than Mann (P < .05). Iod 320+Mann caused VF later than Mann+Na/Ca or Mann (P <
      .02 and P < .01). Mann+Na/Ca caused VF later than Mann (P < .05). CONCLUSION: The
      results fit with a concept that VF starts when the electrolyte composition of the
      interstitial fluid in the myocardium is sufficiently nonphysiologic. The more
      physiologic the electrolyte composition of the perfusion fluid, and the higher
      its viscosity, the slower the composition of the interstitial fluid will be
      changed, and VF will occur later (or not at all).

PMID- 15147626
TI  - Consulting.

PMID- 15147627
TI  - Subspecialization consulting.

PMID- 15147628
TI  - In vivo imaging with fluorescent proteins: the new cell biology.
AB  - We propose a new cell biology where the behavior of cells can be visualized in
      the living animal. An example of the new cell biology is dual-color fluorescence
      imaging using red fluorescent protein (RFP)-expressing tumors transplanted in
      green fluorescent protein (GFP)-expressing transgenic mice. These models show
      with great clarity the details of tumor-stroma interactions and especially tumor
      induced angiogenesis, tumor-infiltrating lymphocytes, stromal fibroblasts and
      macrophages. Another example is the color coding of cells with RFP or GFP such
      that both cell types can be simultaneously visualized in vivo. Stem cells can
      also be visualized and tracked in vivo. Mice in which the regulatory elements of
      the stem-cell marker nestin drive GFP enable nascent vasculature to be visualized
      interacting with transplanted RFP-expressing cancer cells. Nestin-driven GFP
      expression can also be used to visualize hair follicle stem cells. Dual-color
      cells expressing GFP in the nucleus and RFP in the cytoplasm enable real-time
      visualization of nuclear-cytoplasm dynamics including cell cycle events and
      apoptosis. Multiple-color labeling of cells will enable multiple events to be
      simultaneously visualized in vivo including gene expression, ion fluxes, protein
      and organelle trafficking, chromosome dynamics and numerous other processes
      currently still only studied in vitro.

PMID- 15147629
TI  - The need for metabolic mapping in living cells and tissues.
AB  - The ultimate activity of an enzyme depends on many regulatory steps from
      transcription of the gene up to complex formation of the enzyme. Therefore, gene
      expression (mRNA levels) or protein expression (protein levels) are not reliable
      parameters to predict the functional activity of an enzyme. Activity measurements
      in cell homogenates or in frozen or fixed (and thus dead) cell preparations are
      not appropriate either because post-translational regulation mechanisms that
      exist in living cells may be lost by homogenization or freezing or chemical
      fixation of cells. Therefore, metabolic mapping in living cells or, in other
      words, visualization and quantification using microscopy and image analysis of
      enzyme reactions in living cells is the approach of choice to understand the
      functional role of enzymes in vivo as is demonstrated here with a number of
      examples in recent literature.

PMID- 15147630
TI  - Carbohydrate involvement in cellular interactions in sea urchin gastrulation.
AB  - The sea urchin embryo is a model for studying cellular interactions that occur in
      higher organisms because of its availability, transparency, and accessibility to
      molecular probes. In previous studies, we found that the mannose/glucose-binding
      lectin Lens culinaris agglutinin entered living sea urchin embryos, bound to
      specific cell types and caused exogastrulation, when the developing gut
      (archenteron) falls out of the embryo proper. We have proposed that the lectin
      bound to sugar-containing ligands, thus preventing attachment of the archenteron
      to the blastocoel roof, resulting in exogastrulation. Here, we have continued our
      study of cellular interactions in this model using Lytechinus pictus sea urchin
      embryos, and have found that inhibitors of glycoprotein/proteoglycan synthesis,
      tunicamycin and sodium selenate, and the specific glycosidases, beta-amylase,
      alpha-glucosidase, and alpha-mannosidase, all inhibit archenteron organization,
      elongation, and attachment to the blastocoel roof in viable swimming embryos. We
      also show that single cells obtained by disaggregation of 32-h-old sea urchin
      embryos bind to L. culinaris agglutinin- and concanavalin A-derivatized beads;
      the binding is blocked by alpha-methyl mannose, but not l-fucose. These cells
      also bind to beads derivatized with mannan. These results provide evidence for a
      role of carbohydrate-containing molecules in cellular interactions in sea urchin
      gastrulation. In a second set of experiments, we found that the supernatant
      obtained by disaggregation of 24-32-h-old L. pictus embryos in calcium- and
      magnesium-free sea water contains molecules that cause exogastrulation,
      archenteron disorganization, inhibition of archenteron elongation and inhibition
      of archenteron attachment to the blastocoel roof in viable swimming embryos. We
      propose that the supernatant contains ligands and/or receptors that mediate
      archenteron development and attachment to the blastocoel roof and are released
      when embryos are disaggregated into single cells. These studies may lead to a
      better understanding of the molecular basis of mechanisms that control cellular
      interactions during development.

PMID- 15147631
TI  - A novel pattern of pp65-positive cytomegalic endothelial cells circulating in
      peripheral blood from a renal transplant recipient.
AB  - The present study reports a novel pattern of cytomegalic endothelial cells (CEC)
      in peripheral blood from a female renal transplant recipient infected with human
      cytomegalovirus (HCMV), which has not been reported previously. Localization of
      specific early antigen of HCMV, pp65 antigen, was examined by
      immunohistochemistry. Staining of an endothelial cell marker (CD34) was used to
      characterize endothelial cells. It is demonstrated that many leukocytes
      surrounded and adhered to a protein-like material, in which pp65-positive CEC
      were detected. The composition and function of this protein-like material are yet
      unknown. The patient lacked clinical symptoms of HCMV disease. Furthermore,
      similar localization patterns were found in other renal transplant recipients
      suffering from HCMV infections as determined by real-time PCR to detect HCMV DNA
      in blood. These patients showed no or only minor clinical symptoms of HCMV
      infection. It is suggested that these novel localization patterns of CEC may play
      a role in the host defense in patients infected with HCMV, but the exact relation
      between HCMV infection and CEC formation needs further investigation.

PMID- 15147632
TI  - Immunofluorescence localization of prolyl 4-hydroxylase isoenzymes and type I and
      II collagens in bone tumours: type I enzyme predominates in osteosarcomas and
      chondrosarcomas, whereas type II enzyme predominates in their benign
      counterparts.
AB  - Prolyl 4-hydroxylase is the key enzyme of synthesis of collagens. Hydroxylation
      of a sufficient number of proline residues to hydroxyproline is necessary for the
      stability of triple helices in collagenous proteins, because non-hydroxylated non
      triple-helical collagen polypeptide chains are degraded intracellularly. We
      studied 15 primary chondrosarcomas and osteosarcomas, 17 benign bone tumours and
      one case of fibrous dysplasia and chordoma using immunofluorescence staining with
      antibodies against the alpha(I) and alpha(II) subunits of type I and II prolyl 4
      hydroxylases, and with antibodies against collagen types I and II. Type I prolyl
      4-hydroxylase was found to be the predominant isoenzyme in both types of bone
      sarcoma, whereas the type II enzyme was more readily expressed by benign tumours.
      A feature of collagen staining, that was common to both sarcoma types, was that
      collagen types I and II were mainly found within cancer cells and were rarely
      present extracellularly. Extracellular collagen staining was more obvious in
      benign tumours. The results show that expression of prolyl 4-hydroxylase
      isoenzymes is altered in bone sarcomas as compared with normal bone tissue.
      Chondrous cells, which normally express mainly the type II isoenzyme, switch
      their expression pattern to that of type I. The findings provide evidence that
      type I is the major isoenzyme in malignant bone tumours, and probably in
      malignant neoplasms in general. The pattern of enzyme expression is considered to
      be associated with dedifferentiation of cancer cells.

PMID- 15147633
TI  - Expression pattern of apolipoprotein M during mouse and human embryogenesis.
AB  - Apolipoprotein M (apoM) is a recently discovered human apolipoprotein
      predominantly present in high-density lipoprotein (HDL), and in minor proportions
      in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The
      gene encoding apoM is present in all mammalian genomes. The identity of the apoM
      gene of human, rat and mouse is over 80%. However, the (patho)physiological
      functions of apoM are unknown yet. In the present study, we investigated apoM
      expression patterns during mouse and human embryogenesis. ApoM transcripts were
      detectable in mouse embryos from day 7.5 to day 18.5. ApoM was expressed at low
      levels at day 7.5, its expression increased significantly at day 9.7, decreased
      at day 10.5, and then increased continually up to day 18.5. ApoM-positive cells
      appeared mainly in liver of day-12 embryos as detected by in situ hybridization.
      In day-15 embryos, apoM was expressed in both liver and kidney. During human
      embryogenesis, apoM was mainly expressed in liver and kidney and little was found
      in small intestine as determined by mRNA array of human fetal normal tissues.
      ApoM was also detected in stomach and skeletal muscle in early stages of
      embryogenesis (3-5 months).

PMID- 15147634
TI  - Cyclosporine-A treatment prevents apoptosis in rat lumbar ganglion cells.
AB  - We evaluated the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 in
      lumbar ganglion cells of rats by immunohistochemistry under normal conditions and
      after 7, 14 and 21 days of cyclosporine-A treatment (7 and 15 mg/kg/daily). In
      normal rats, Bax was weakly expressed in all types of neurons, whereas satellite
      cells showed moderate immunostaining. Bcl-2 expression was weak in type A neurons
      and weak or moderate in type B and C neurons and also into satellite cells. In
      cyclosporine-A-treated rats, we found changes in Bax staining of neurons: type A
      neurons and type B neurons were weakly stained, whereas type C neurons were
      moderately stained. Bax expression in satellite cells was moderate after 7 days
      of treatment and increased strongly after 14 and 21 days of treatment. Bcl-2
      expression increased significantly in neurons after 14 and even more after 21
      days of treatment with 7 mg/kg cyclosporine-A, mainly in type B and C neurons.
      With 15 mg/kg cyclosporine-A, Bcl-2 increased moderately in type A and B neurons
      and strongly in type C neurons only after 7 days. After 14 and 21 days, Bcl-2
      expression was moderate in type A neurons whereas it was strong or even very
      strong in type B and C neurons. Satellite cells showed a moderate increase in Bcl
      2 after 7 and 14 days of treatment whereas after 21 days, expression was strong.
      We conclude that (1) in normal conditions, Bax and Bcl-2 were differently
      expressed in neurons and satellite cells; (2) cyclosporine-A treatment rapidly
      enhanced Bax expression in satellite cells only, whereas Bcl-2 expression
      increased moderately in type A neurons and was strongly expressed in type B and C
      neurons; (3) cyclosporine-A has a protective role in neurons but not in satellite
      cells; and (4) the neuroprotective role of cyclosporine-A is dose dependent.
      Furthermore, the strong expression of Bax in satellite cells can explain the
      temporary nature of the neurotoxic effect commonly observed after cyclosporine-A
      administration.

PMID- 15147635
TI  - Oestrous cycle-regulated expression of inositol 1,4,5-trisphosphate receptor type
      2 in the pig ovary.
AB  - The inositol 1,4,5-trisphosphate receptor type 2 (IP(3)R-2) is an intracellular
      Ca(2+) release channel responsible for mobilizing of Ca(2+) from intracellular
      storage sites and plays a key role in biological processes such as fertilization,
      cell differentiation, and growth. To study the cell-type-specific IP(3)R-2
      expression in porcine ovaries during different phases of the oestrous cycle, we
      used reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. A total of 24 ovaries from gilts were collected in early
      luteal, mid-luteal, and follicular phases of the oestrous cycle. When amplified
      with the primers common to IP(3)R-2, a RT-PCR product of the expected size
      (approximately 388 bp) was clearly detected in the follicular and early luteal
      phase of the oestrous cycle, but there was no detectable PCR product in the
      corpus luteum of the mid-luteal phase of the oestrous cycle. Immunohistochemical
      studies showed that IP(3)R-2 protein is expressed in granulosa cells and theca
      cells of growing follicles. IP(3)R-2 immunostaining was first detected during the
      late pre-antral stage in granulosa and theca cells. Granulosa cell IP(3)R-2
      expression increased from the pre-antral to mid-antral stage, but was strongly
      reduced in pre-ovulatory follicles. In the developing corpus luteum, intense
      IP(3)R-2 immunostaining was also present in luteal cells, but undetectable in mid
      luteal corpora lutea. Furthermore, oocytes, atretic follicles and regressed
      corpora lutea were negative for IP(3)R-2. Our results indicate that the
      expression of the IP(3)R-2 protein was downregulated in terminally differentiated
      granulosa cells of pre-ovulatory follicles when granulosa cells lose follicle
      stimulating hormone responsiveness. Therefore, we strongly suggest that IP(3)R-2
      may play an important role in the initiation and propagation of intracellular
      Ca(2+) signals during follicular development of the pig.

PMID- 15147636
TI  - Differentiation of rat skeletal muscle fibres during development and ageing.
AB  - The purpose of the present study was to determine at which point in the period
      from embryonic day 21 up to postnatal day (PD) 75, the different fibre types and
      subtypes are detectable in rat extensor digitorum longus, soleus and
      gastrocnemius muscles using immunohistochemical, enzyme histochemical and
      cytophotometrical methods. Moreover, fibre type-specific changes in metabolic
      profile and changes in fibre type population during postnatal development were
      analysed. Before birth, no clear differentiation of fibre types was found. At PD
      1, slow and fast fibres were typed by antibodies against neonatal, slow and fast
      myosin heavy chains (MHCs). At PD 8, the different ATPase activities of slow and
      fast MHCs after alkaline preincubation were detected histochemically. At PD 21,
      differences in acid stability of ATPase activity of fast MHC isoforms revealed
      the fast subtypes IIA and IIB (including IIX). At this age, also differences in
      metabolic properties (oxidative and glycolytic enzyme activities) of fibres were
      detected for the first time by cytophotometry classifying the fibres into SO, FOG
      I, FOG II and FG. Before the age of 21 days, the fast fibres were metabolically
      undifferentiated. During further development and ageing, the population of FG
      fibres with high glycolytic activity increased at the expense of FOG fibres
      suggesting FOG to FG transformation. Cytophotometrical measurements revealed that
      the muscle fibres developed their highest contractile, oxidative and glycolytic
      activity at PD 21, the time of weaning. In this way, muscle fibres may be
      prepared for the higher demands for posture and mobility after leaving the nest.

PMID- 15147637
TI  - Clonal xenobiotic resistance during pollution-induced toxic injury and
      hepatocellular carcinogenesis in liver of female flounder (Platichthys flesus
      (L.)).
AB  - Juvenile and adult female flounder (Platichthys flesus (L.)) were caught either
      in the estuary of the most polluted European river, the Elbe, or as controls in a
      reference site to study pollution-induced xenobiotic resistance in their livers
      in relation to pathological alterations. In juvenile fish, livers displayed
      reversible and irreversible degenerative toxipathic lesion types but never showed
      (pre)neoplastic changes. Tumour frequencies up to 70% were found macroscopically
      in livers of adult female flounder which had progressed to adenomas and
      carcinomas in the most polluted site. Because male adult flounder show only up to
      50% of livers containing early preneoplastic foci but never malignancies, we
      focussed our study on female individuals. (Pre)neoplastic changes ranged from
      early eosinophilic foci to basophilic foci, adenomas and hepatocellular
      carcinomas. Adenomas were generally eosinophilic whereas carcinomas were mainly
      basophilic. These phenotypical sequential changes strongly resemble those found
      in chemically-induced liver carcinogenesis in mammals. Characteristic mutations
      known from mammalian cancers have not been found so far in these flounder livers.
      Therefore, we investigated whether epigenetic events had induced a metabolic
      "resistant phenotype" of (pre)malignant cancer cells during hepatocellular
      carcinogenesis. With a quantitative immunohistochemical approach, we studied
      expression of P-glycoprotein (P-gp)-mediated multixenobiotic resistance (MXR),
      cytochrome P4501A1, glutathione-S-transferase-A which are key proteins in
      xenobiotic metabolism and elimination. Glucose-6-phosphate dehydrogenase (G6PDH)
      activity, the major source of the reducing power NADPH which is needed for
      biotransformation, oxyradical scavenging and biosynthesis, was detected as well.
      We observed upregulation of G6PDH activity already in early preneoplastic
      eosinophilic foci and subsequent further upregulation in basophilic foci and
      carcinomas. P-gp started to become overexpressed in basophilic foci and was
      overexpressed even more strongly in carcinomas and their invasively-growing
      protrusions (satellites). In carcinomas, P-gp protein was predominantly present
      in membranes of lysosomes which are the intracellular sites of deposition of
      xenobiotics. CYP450 was reduced whereas GST-A was increased in these carcinomas.
      Progression towards malignancy was positively correlated with levels of mitogenic
      organochlorines in these livers which are "fingerprint contaminants" of the river
      Elbe. We conclude that (pre)neoplastic hepatocytes in female flounder acquire
      growth advantages over normal hepatocytes by epigenetic metabolic adaptations
      during liver carcinogenesis as a result of chronic exposure to (pro)carcinogens
      in the polluted habitat.

PMID- 15147638
TI  - An immunohistochemical study of endocrine cells in the alimentary tract of the
      grass lizard, Takydromus wolteri Fischer (Laceridae).
AB  - Distribution patterns and the relative frequency of different types of endocrine
      cells were demonstrated in the alimentary tract of the grass lizard, Takydromus
      wolteri, using nine specific antibodies raised against mammalian regulatory
      peptides. The alimentary tract of the lizard was divided into six portions from
      the esophagus to the rectum. Most endocrine cells were found in the epithelial
      lining and were generally spindle shaped with long cytoplasmic processes ending
      in the lumen (open cell type), whereas cells that were spherical in shape (closed
      cell type) were occasionally found in gastric, esophageal and intestinal glands.
      Endocrine cells were stained for the following regulatory peptides: bovine Sp
      1/chromogranin (BCG), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8,
      glucagon, insulin, human pancreatic polypeptide (HPP) and secretin. Cells stained
      for BCG and serotonin were present throughout the entire gastrointestinal tract
      and they occurred with the highest frequency in stomach and pylorus,
      respectively. Somatostatin-positive cells were detected throughout the entire
      gastrointestinal tract except for the esophagus and large intestine, and were
      most predominant in pylorus and duodenum. Cells stained for gastrin were
      restricted to the pylorus and duodenum and occurred with a relatively low
      frequency. CCK-8-positive cells were observed from pylorus to small intestine and
      showed the highest frequency in the pylorus. Glucagon- and insulin-containing
      cells were located in duodenum and small intestine but were found only rarely.
      HPP-stained cells were detected in duodenum and small intestine with the highest
      frequency in duodenum. Cells stained for secretin were restricted to duodenum and
      were found only rarely. In conclusion, distribution patterns and the relative
      frequency of these endocrine cells correspond well with previous reports on
      distribution patterns of endocrine cells in reptile species but some deviating
      patterns were also observed.

PMID- 15147640
TI  - Policy and program coordination: a shared challenge with miles yet to go.

PMID- 15147641
TI  - Enhancing HIV/AIDS and STD prevention through program integration.

PMID- 15147642
TI  - Opportunities and pitfalls in integration of family planning and HIV prevention
      efforts in developing countries.

PMID- 15147644
TI  - The role of quantitative policy analysis in HIV prevention technology transfer.

PMID- 15147643
TI  - Bioterrorism preparedness coordination: an ataxic saga continues.

PMID- 15147645
TI  - No product? No program!

PMID- 15147646
TI  - The Massachusetts HIV, hepatitis, addiction services integration (HHASI)
      experience: responding to the comprehensive needs of individuals with co
      occurring risks and conditions.
AB  - Categorical funding mechanisms traditionally used to fund public health programs
      are a challenge to providers serving individuals with complex needs that often
      span multiple service areas. Integration--a formalized, collaborative process
      among service systems--responds to the challenge by decreasing fragmentation of
      care and improving coordination. In 2000, the Massachusetts Department of Public
      Health (MDPH) received a one-year planning grant from the federal Substance Abuse
      and Mental Health Services Administration (SAMHSA) to evaluate opportunities for
      integrating HIV/AIDS programs and substance abuse treatment programs. The project
      was later expanded to include viral hepatitis programming. Outcomes include the
      development of a strategic plan, joint procurement initiatives, and an ongoing
      commitment to sustain inter-bureau integration efforts, even in the face of
      substantial budget reductions. Integrated approaches can promote greater
      efficiency, improving communication and coordination among clients, providers,
      and government funding agencies.

PMID- 15147647
TI  - An invisible barrier to integrating HIV primary care with harm reduction
      services: philosophical clashes between the harm reduction and medical models.
AB  - Overall AIDS mortality in the United States has declined in recent years, but
      declines have not been consistent across all populations. Due to an array of
      barriers to care, minorities and poor people who are active substance users have
      not benefited as others have from advances in the treatment of HIV disease. One
      way to address this problem is to integrate HIV primary care into harm reduction
      programs that already effectively serve this population. Such collaborations,
      however, are difficult to initiate and sustain. Philosophical differences between
      the medical model and the harm reduction model, which often remain invisible to
      the parties involved, underlie these difficulties. This article addresses the
      issue by describing a partnership in the Bronx, NY, between CitiWide Harm
      Reduction Inc. (CitiWideHR) and the Montefiore Medical Center. It focuses
      specifically on the sources of philosophical differences between models, and
      briefly assesses the potential for successful collaborations of this sort.

PMID- 15147648
TI  - Special action groups for policy change and infrastructure support to foster
      healthier communities on the Arizona-Mexico border.
AB  - As part of efforts to help stem the rising tide of diabetes among Hispanic
      Americans living in Arizona-Mexico border communities, the Border Health
      Strategic Initiative was launched to foster community-based approaches to
      diabetes prevention and control. A major thrust of the initiative was
      establishment of special community action groups (SAGs) to help stimulate policy
      change and sustain interventions designed to reduce the risk of diabetes and its
      complications. The SAGs met regularly for more than two years, focusing primarily
      on policies that encourage development of an infrastructure to support physical
      activity and healthier nutrition. Through involvement with planning commissions,
      parks and recreation, and private companies, two community development block
      grants were obtained to support new walking trails. The SAGs also encouraged
      elementary schools to improve physical education and change vending machine
      products, and grocery store owners and managers to allow the demonstration and
      promotion of healthier foods. These groups, focused on policy and infrastructure
      change within their communities, may be the glue needed to hold comprehensive
      community health promotion efforts together.

PMID- 15147649
TI  - Integrating mental health services into primary HIV care for women: the Whole
      Life project.
AB  - The high rate of mental health problems in HIV-infected women jeopardizes the
      health of this vulnerable population, and constitutes a mandate for integrating
      mental health services into HIV primary care. The Whole Life project-a
      collaboration of the departments of Psychiatry and Obstetrics/Gynecology at the
      University of Miami School of Medicine-successfully integrated mental health
      services into primary HIV care for women. This article describes the conceptual
      framework of the integration, implementation strategies, effects of the service
      integration, and lessons learned. Funded by the Health Resources and Services
      Administration (HRSA) as a Special Program of National Significance (SPNS), Whole
      Life efforts have been sustained beyond the demonstration funding period as a
      result of the changes brought about in organizational structures, service
      delivery, and the providers' conceptualization of health for HIV-infected women.

PMID- 15147650
TI  - Conducting interdisciplinary research to promote healthy and safe employment in
      health care: promises and pitfalls.
AB  - Due to the complexity of human health, emphasis is increasingly being placed on
      the need for and conduct of multidisciplinary and/or interdisciplinary health
      research. Yet many academic and research organizations--and the discipline
      specific associations and journals--may not yet be prepared to adopt changes
      necessary to optimally support interdisciplinary work. This article presents an
      ongoing interdisciplinary research project's efforts to investigate mechanisms
      and pathways that lead to occupational health disparities among healthcare
      workers. It describes the promises and pitfalls encountered during the
      research,and outlines effective strategies that emerged as a result. Lessons
      learned include: conflict resolution regarding theoretical and methodological
      differences; establishing a sense of intellectual ownership of the research, as
      well as guidelines for multiple authorship; and development and utilization of
      protocols, communication systems, and tools. This experience suggests a need for
      the establishment of supportive structures and processes to promote successful
      interdisciplinary research.

PMID- 15147651
TI  - Partnerships within and beyond universities: opportunities and challenges:
      commentary on "conducting interdisciplinary research to promote healthy and safe
      employment in healthcare: promises and pitfalls".

PMID- 15147652
TI  - The quarantine war: the burning of the New York Marine Hospital in 1858.

PMID- 15147653
TI  - Reducing discrimination affecting persons with limited English proficiency:
      federal civil rights guidelines under Title VI of the 1964 Civil Rights Act.

PMID- 15147654
TI  - Regurgitant mitral valve and 3D echocardiography--meant for each other?

PMID- 15147655
TI  - Risk stratification by stress echocardiography: a whiter shade of pale?

PMID- 15147656
TI  - Echocardiographic overestimation of left ventricular mass using second harmonic
      imaging.

PMID- 15147658
TI  - Echocardiographic assessment of left ventricular midwall mechanics in
      spontaneously hypertensive rats.
AB  - AIMS: The present study was attempted to determine whether LV midwall mechanics
      yielded different conclusions about LV systolic function than the assessment of
      endocardial LV mechanics by echocardiography in spontaneously hypertensive rats
      (SHR). METHODS AND RESULTS: Thirty-six (18 Wistar normotensive (W), 18 [SHR])
      anesthetized rats were studied with two-dimensional directed M-mode
      echocardiogram to analyze LV structure (LV diameter, left ventricular wall
      thickness and LV mass [LVM]) and LV function (endocardial shortening [ES] and
      midwall shortening [MS]). Measurements were made from three consecutive cardiac
      cycles on the M-mode tracings. There was no significant difference in LV
      dimension. LVM was higher in SHR (SHR: 595 +/- 111 mg, W: 413 +/- 83 mg--p <
      0.01). ES was higher in SHR (SHR: 64.1 +/- 6%, w: 58.2 +/- 4%--p < 0.01), whereas
      no significant difference was found in MS (SHR: 24 +/- 4%, W: 27.6 +/- 4%--ns).
      Twelve of 18 (66%) SHR showed endocardial shortening higher than normally
      predicted, compared with 3/18 (16%) with observed enhanced MS (p < 0.01).
      CONCLUSION: These results suggest that the analysis of midwall mechanics by echo
      allows us to better understand the LV performance in SHR and that the exaggerated
      endocardial motion could not represent a really supernormal systolic performance.

PMID- 15147659
TI  - Transthoracic echocardiography using second harmonic imaging with Valsalva
      manoeuvre for the detection of right to left shunts.
AB  - AIMS: To assess transthoracic echocardiography (TTE) using second harmonic
      imaging with Valsalva manoeuvre compared to transesophageal echocardiography
      (TEE) for the diagnosis of right to left cardiac and pulmonary shunts. METHODS
      AND RESULTS: One hundred and ten patients referred for TEE underwent TTE with
      bubble contrast. Bubbles in the left atrium within three cardiac cycles were
      considered diagnostic for a patent foramen ovale (PFO) and later as a pulmonary
      shunt. Greater than 20 bubbles in the left atrium was considered a large shunt
      and less than 20 a small shunt. TEE was performed immediately afterwards and read
      blinded to the TTE results. Pick-up rates were similar with 19 TEE positive (13
      PFO) and 18 TTE positive (14 PFO) patients. There were five TEE positive/TTE
      negative cases who had significantly poorer TTE image quality score (2.7 +/- 0.8
      vs 1.9 +/- 0.6, p < 0.05). There were six TEE negative/TTE positive cases, two
      cases requiring Valsalva manoeuvre to become positive. The Valsalva manoeuvre
      significantly increased the number of bubbles shunting (10 +/- 11 vs 20 +/- 19, p
      < 0.005). CONCLUSION: TTE with Valsalva manoeuvre is as good as TEE in diagnosing
      shunts. Valsalva manoeuvre increases the size of shunt. Both techniques produce
      false negative results.

PMID- 15147660
TI  - Diastolic function in Chagas' disease: an echo and tissue Doppler imaging study.
AB  - AIMS: With the purpose of studying left ventricular filling in Chagas' disease
      (Chd), we evaluated 169 patients with Chd using echocardiography and Doppler and
      tissue Doppler imaging (TDI). METHODS AND RESULTS: The patients were divided into
      four groups according to the pattern of left ventricular filling: Group 0--normal
      filling pattern, Group 1--abnormal relaxation, Group 2--pseudonormal flow
      pattern, and Group 3--restrictive pattern. All patients were submitted to TDI of
      the basal portion of the left ventricle's walls. Diastolic dysfunction was found
      in 21.3% of the patients, with a strong correlation between the worsening of
      diastolic function and ejection fraction (r = 0.78, P < 0.001). TDI septal e'
      wave measurement was the best method for the detection of any kind of diastolic
      dysfunction. Considering a cut-off point of 11 cm/s, a reduced e' wave value has
      97% sensitivity, 84% specificity, 62% positive predictive value, and 99% negative
      predictive value. The septal E/e' ratio was the best index for the detection of
      advanced diastolic dysfunction. Considering a cut-point of 7.2, an elevated E/e'
      ratio has 100% sensitivity, 88% specificity, 54.2% positive predictive value, and
      100% negative predictive value. CONCLUSION: This study showed the
      characterization of the various patterns of left ventricle diastolic function by
      echocardiography and Doppler in Chagas' disease and the usefulness of TDI in the
      assessment of diagnosis of diastolic dysfunction in this disease.

PMID- 15147661
TI  - Effect of harmonic imaging on the measurement of ultrasonic integrated
      backscatter and its interpretation in patients following myocardial infarction.
AB  - BACKGROUND: Recently, we have demonstrated that cyclic variation in ultrasonic
      integrated backscatter (IBS) can be used to predict patency of the infarct
      related artery (IRA) post-acute myocardial infarction (AMI). Second harmonic
      imaging has become widely available on ultrasound machines and enhances
      endocardial definition. The effect of harmonic imaging on the measurement and
      interpretation of cyclic IBS is unknown. METHODS AND RESULTS: Twenty-eight
      patients were studied post-AMI. Cyclic IBS was measured in myocardial segments
      supplied by the IRA as well as in remote segments with normal myocardial function
      in both fundamental and second harmonic modes. Harmonic imaging increased the
      measurement of cyclic IBS in IRA as well as normal myocardial territories.
      However, the difference in cyclic IBS between IRA and normal myocardial
      territories remained unchanged. CONCLUSION: Second harmonic imaging increases the
      measurement of cyclic IBS. However, the interpretation of these data is unchanged
      in the setting of AMI. It is important that repeated studies in the same patient
      are performed in the same mode (fundamental or harmonic) as the values are not
      interchangeable.

PMID- 15147662
TI  - Comparison of early diastolic mitral annular velocity and flow propagation
      velocity in detection of mild to moderate left ventricular diastolic dysfunction.
AB  - BACKGROUND: Pulsed wave tissue Doppler echocardiography (PW-TDE) and color M-mode
      are new Doppler methods for left ventricular (LV) diastolic function assessment.
      To date, few studies have compared the data obtained by these methods in the same
      series of patients and compared them to the current clinical reference method of
      detecting LV diastolic function. AIMS: To determine the utility of PW-TDE and
      color M-mode parameters in the assessment of LV diastolic function in the typical
      patient population encountered in daily clinical practice and to compare their
      discriminating power. METHODS: Early diastolic septal mitral annular velocity
      (Em) determined by PW-TDE and color M-mode flow propagation velocity (Vp) were
      measured in 86 male patients and compared to LV filling patterns obtained using
      standard Doppler indices. Values of Em < 0.08 m s(-1) and Vp < 0.5 m s(-1) were
      considered as markers of abnormal LV diastolic function. RESULTS: A value of Em <
      0.08 m s(-1) distinguished mild to moderate LV diastolic dysfunction with higher
      sensitivity and specificity than Vp < 0.5 m s(-1) (96% and 87% vs. 73% and 84%,
      respectively). A comparison of receiver operating characteristic curves showed a
      significant difference for areas under the curve in favor of Em (P < 0.01). In a
      stepwise multiple logistic regression analysis, a pseudonormal filling pattern
      and an EF > 60% were identified as significant predictors of Vp false negative
      results (p < 0.05). CONCLUSIONS: Em appears to be superior to Vp in the detection
      of mild to moderate LV diastolic dysfunction. Vp failed to detect abnormal LV
      diastolic function in particular in patients with preserved LV systolic function
      and a pseudonormal filling pattern type.

PMID- 15147663
TI  - Identifying patients without favourable long-term outcome among those with
      medically stabilized unstable angina and a negative dipyridamole stress
      echocardiogram.
AB  - AIMS: Patients with medically stabilized unstable angina and a negative stress
      echocardiogram have a favourable outcome as a whole. This study sought to
      identify which subsets of patients are associated with serious events at long
      term within this population. METHODS AND RESULTS: We studied and followed-up 128
      patients (mean 2.2 +/- 1.3 years) with medically stabilized unstable angina and a
      negative dipyridamole stress echocardiogram. Cumulative survival rates were 98.2
      +/- 1.3%, 96.0 +/- 2.2% and 93.2 +/- 3.2%, at 1, 2 and 4 years, respectively.
      Freedom from events (death, myocardial infarction, and revascularization) were
      98.2 +/- 1.3%, 96.0 +/- 2.2% and 86.3 +/- 6.0%, at 1, 2, and 4 years,
      respectively. Cumulative mortality rate was higher in men (3.6 +/- 2.5%, 8.5 +/-
      4.1%, and 12.2 +/- 5.4% at 1, 2, and 4 years, vs. 0% at the end of the follow-up
      in women; p = 0.034), and in those with previous myocardial infarction (4.3 +/-
      4.3%, 9.1 +/- 6.2%, and 18.2 +/- 2.3% at 1, 2 and 4 years, vs. 1.1 +/- 1.1%, 2.9
      +/- 2.1%, and 2.9 +/- 2.1% in those without previous myocardial infarction,
      respectively; p = 0.047). CONCLUSION: Among patients with medically stabilized
      unstable angina and a negative dipyridamole stress echocardiogram, male gender
      and previous myocardial infarction are associated with a non-favourable outcome.

PMID- 15147664
TI  - Three-dimensional echocardiography is superior to multiplane transoesophageal
      echo in the assessment of regurgitant mitral valve morphology.
AB  - AIMS: Transoesophageal echocardiography (TOE) plays a vital role in the
      assessment of mitral valve morphology. However, the accuracy of TOE may be
      limited by inadequate recognition of all segments. We aimed to evaluate the role
      of three-dimensional (3D) echocardiography in this respect. METHODS AND RESULTS:
      Seventy-five patients were studied prior to mitral valve repair surgery. A
      scoring protocol was devised for recognition of the eight Carpentier segments
      (0=inadequate for analysis, 1=adequate, 2=good). Using surgical findings as the
      gold standard, TOE and 3D were compared for adequate recognition scores and
      accurate detection of functional morphology. Adequate recognition was more
      frequently obtained with 3D imaging (97% of segments by 3D c.f. 90% by TOE; p =
      0.000). The major difference was seen at the commissures (adequate scores in
      143/150 commissures by 3D c.f. 90/150 by TOE; p = 0.000). 3D matched more closely
      to surgical findings, achieving exact functional description in 92% of segments
      vs 79% segments with TOE (p = 0.000). This incremental value of 3D was seen in
      both commissures and the anterior leaflet but not in the posterior leaflet.
      CONCLUSIONS: In this study 3D was superior not only for complete recognition of
      the mitral valve but also for the accurate localisation and identification of
      pathology.

PMID- 15147665
TI  - Diagnosis of suspected cardiac echinococcosis with negative serologies: role of
      transthoracic, transesophageal, and contrast echocardiography.
AB  - The early recognition and treatment of hydatid disease of the heart is important
      as it can result in potentially lethal complications. We present the clinical and
      echocardiographic features of a 71 year old Afghanistani man who presented with
      left-sided chest pain. Transthoracic (TTE), transesophageal (TEE), and contrast
      echo demonstrated a calcified cystic structure within the distal anterior septum
      consistent with an echinococcal cyst, despite negative serologies. Treatment
      strategies for this patient are discussed.

PMID- 15147666
TI  - Pulmonary artery dissection in a patient with Eisenmenger syndrome treated with
      heart and lung transplantation.
AB  - We report the case of a patient with known Eisenmenger syndrome due to congenital
      ventricular septal defect, who developed pulmonary artery dissection. The patient
      was successfully treated with heart and lung transplantation.

PMID- 15147667
TI  - Aortic valve regurgitation due to cusp aneurysm: a case report.
AB  - Two-dimensional echocardiography is a valuable tool in visualizing and monitoring
      aortic valve and root abnormalities. We present a rare case of a patient with
      massive aortic regurgitation due to cusp aneurysm, which was accurately diagnosed
      by echocardiography and treated by valve replacement. A complicated course with
      recurrent aneurysms of the aortic wall after aortic valve replacement was
      remarkable in this case. Although different possible etiologies could not be
      determined, endocarditis and/or aortitis may be the most likely explanation of
      the complicated and finally fatal course of this patient.

PMID- 15147668
TI  - No accounting for taste: host preference in malaria vectors.

PMID- 15147669
TI  - Problems in speciation in the genus Blastocystis.

PMID- 15147670
TI  - Update on immunological tests for lymphatic filariasis.

PMID- 15147671
TI  - Analyzing the structure of biodiversity.

PMID- 15147673
TI  - Immunodiagnostic approaches for detecting Taenia solium.

PMID- 15147675
TI  - Cross-species regulation of Plasmodium parasitaemia cross-examined.

PMID- 15147677
TI  - Genetics and visceral leishmaniasis in the Sudan: seeking a link.

PMID- 15147678
TI  - Microsporidia: how can they invade other cells?

PMID- 15147679
TI  - Manipulation of apoptosis in the host-parasite interaction.

PMID- 15147680
TI  - Microarrays and stage conversion in Toxoplasma gondii.

PMID- 15147681
TI  - Solution structure of folic acid. Molecular mechanics and NMR investigation.
AB  - The structure of folic acid in solution was investigated by nuclear magnetic
      resonance (NMR) and theoretical calculations. Dynamical information and
      geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear
      NOESY spectra and hetero-nuclear 1H-13C NOE experiments. This set of experimental
      data was used for the molecular mechanics and molecular dynamic calculations. The
      accuracy of the final structure was established by the R(NMR) factor, which was
      calculated comparing the experimental NOESY cross-peaks intensities and the
      corresponding values simulated by using the complete relaxation matrix analysis
      (CORMA) approach.

PMID- 15147682
TI  - Charge transfer complexes of 9-vinyl-carbazole with pi acceptors in homogeneous
      and in micellar solutions.
AB  - The molecular association of 9-vinyl-carbazole (CBZ) with three electron
      acceptors, p-chloranil (CHL), 2,7-dinitro-9-fluorenone (FL), and tetracyano-p
      quinodimethane (TCNQ), is studied in acetonitrile and in micellar aqueous
      solution of sodium dodecyl sulfate (SDS). In both media, stable charge transfer
      (CT) complexes are formed with association constants in the range of 8-500 M(-1).
      CBZ and FL form a 1:2 complex in acetonitrile, but in SDS micelles the
      association is 1:1 due to size restriction and occupancy statistics in the host
      aggregates. The combination of absorption and fluorescence emission spectroscopy
      data indicates that the bimolecular CT complex of CBZ with TCNQ is stabilized in
      two distinct environments of the SDS micelles providing then two separated CT
      absorption bands.

PMID- 15147683
TI  - Synthesis of tetraamino derivative of thiacalix[4]arene and its acid-base
      property studied by UV spectroscopy.
AB  - The tetraamino derivative of thiacalix[4]arene (4) was synthesized and
      characterized. Its acid-base property in water solution was studied by UV
      spectroscopy. The pH distribution regions of several acidic or basic species of 4
      were determined.

PMID- 15147684
TI  - Luminescence emission spectra in the temperature range of the structural phase
      transitions of Na2SO4.
AB  - The spectral properties of Na2SO4 have been studied by means of infrared
      stimulated luminescence (IRSL), thermoluminescence (TL) and radioluminescence
      (RL) in the range of 200-800 nm. The observed changes in the RL emission spectra
      after an annealing treatment (400 degrees C for 1 h) could be linked to thermal
      phase transformations and alkali self-diffusion through the lattice of this salt.
      Despite the complexity of the luminescence spectra structure, five emission bands
      peaked at 330, 345, 385, 460 and 630 nm could be distinguished. The UV-blue TL
      emission of this material exhibits a maximum peaked at 230 degrees C which is
      well correlated with the differential thermal analysis (DTA) and can be
      associated with the thermal transformation of the orthorhombic sodium sulphate
      (Na2SO4) V (thenardite) phase into Na2SO4 III, II and I phases. Taking into
      account the observed changes on the structural phase transition by X-ray
      diffraction (XRD) from 16 degrees C onwards, this material does not show
      satisfactory features for radiation dosimetry, but could be employed for
      temperature calibration of TL readers.

PMID- 15147685
TI  - An infrared and Raman spectroscopic study of natural zinc phosphates.
AB  - Zinc phosphates are important in the study of the phosphatisation of metals.
      Raman spectroscopy in combination with infrared spectroscopy has been used to
      characterise the zinc phosphate minerals. The minerals may be characterised by
      the patterns of the hydroxyl stretching vibrations in both the Raman and infrared
      spectra. Spencerite is characterised by a sharp Raman band at 3516 cm(-1) and
      tarbuttite by a single band at 3446 cm(-1). The patterns of the Raman spectra of
      the hydroxyl stretching region of hopeite and parahopeite are different in line
      with their differing crystal structures. The Raman spectrum of the PO4 stretching
      region shows better band separated peaks than the infrared spectra which consist
      of a complex set of overlapping bands. The position of the PO4 symmetric
      stretching mode can be used to identify the zinc phosphate mineral. It is
      apparent that Raman spectroscopy lends itself to the fundamental study of the
      evolution of zinc phosphate films.

PMID- 15147686
TI  - Lead as own luminescent sensor for determination.
AB  - In our experiments, it was observed that adding bromide to Pb2+ solution of N,N'
      dimethylformamide (DMF), the highly emissive cluster Pb4Br11(3-) can be formed
      and the fluorescence intensity of the formed cluster is proportional to the
      concentration of Pb2+, based on which, a novel, simple approach that uses the
      emission from itself as the sensor for determination of Pb2+ is proposed. Under
      the optimum conditions, the linear range and detection limit is 1.0 x 10(-7) to
      1.0 x 10(-5) mol l(-1) (correlation coefficient r = 0.9997) and 7.6 x 10(-9) mol
      l(-1), respectively. Foreign substrates effects were also investigated. The
      proposed method has been successfully applied to the determination of lead in the
      synthetic samples. The mechanism of the reaction is also studied.

PMID- 15147687
TI  - Solvent effects on infrared spectra of methyl 4-hydroxybenzoate in pure organic
      solvents and in ethanol/CCl4 binary solvents.
AB  - Infrared spectroscopy studies of methyl 4-hydroxybenzoate (MHB) in 17 different
      organic solvents and in ethanol/CCl4 binary solvent were undertaken to
      investigate the solvent-solute interactions. The frequencies of carbonyl
      stretching vibration nu(C=O) of MHB in single solvents were correlated with the
      solvent acceptor number (AN) and the linear solvation energy relationships
      (LSER). The assignments of the two bands of nu(C=O) of MHB in alcohols and the
      single one of that in non-alcoholic solvents were discussed. The shifts of
      nu(C=O) of MHB in ethanol/CCl4 binary solvents showed that several kinds of
      solute-solvent hydrogen bonding interactions coexisted in the mixture solvents,
      with a change in the mole fraction of ethanol in the binary solvents.

PMID- 15147688
TI  - Vibronic structures in the electronic spectra of oligo(phenylene ethynylene):
      effect of m-phenylene to the optical properties of poly(m-phenylene ethynylene).
AB  - At the low temperature, hidden vibronic structures are successfully resolved in
      the absorption and emission spectra of oligo(phenylene ethynylene)s 3-5.
      Identification of the hidden bands allows estimation of the vibrational energy
      gaps in these molecules, which appears to increase with the oligomer conjugation
      length. The remarkable similarity between the absorption profiles of
      diphenylacetylene (3) and 1,3-bis(phenylethynyl)benzene (5), especially at -198
      degrees C, confirms the effectiveness of conjugation interruption at m-phenylene.
      The function of precise conjugation length control via m-phenylene is further
      demonstrated from poly(m-phenylene ethynylene) (PmPE) (6). Even though the number
      of recurring unit (phenylene ethynylene) increases from 2 (for 5) to 12 (for 6),
      the absorption and emission spectra of the latter are nearly identical to that of
      the former.

PMID- 15147689
TI  - An infrared and Raman spectroscopic study of the uranyl micas.
AB  - Vibrational spectroscopy using a combination of infrared and Raman spectroscopy
      has been used to study the uranyl micas also known as the autunite minerals, of
      general formula M(UO2)2(XO4)2.8-12H2O where M may be Ba, Ca, Cu, Fe2+, Mg, Mn2+
      or 1/2(HAl) and X is As or P. Included in these minerals are autunite,
      metautunite, torbernite, meta-torbernite, meta-zeunerite, saleeite and
      sabugalite. Compared with the results of infrared spectroscopy, Raman microscopy
      shows excellent band separation enabling the separation and identification of
      bands attributed to (UO2)2+ units, PO4 and AsO4 units. Common to all spectra were
      bands at around 900 and 818 cm(-1), attributed to the antisymmetric and symmetric
      stretching vibrations of the (UO2)2+ units. Water in autunites is in a highly
      structured arrangement in the interlayer of the uranyl micas. Water molecules are
      differentiated according to the strength of the hydrogen bonds formed between the
      water and the adjacent uranyl-phosphate or uranyl-arsenate surfaces and the
      hydration sphere of the interlayer cation.

PMID- 15147690
TI  - Conformational stabilities and structural parameters of (CH3)(n)CH(3-n) CFO
      molecules.
AB  - Variable temperature (-60 to -100 degrees C) studies of the infrared spectra
      (3500-400 cm(-1)) of propionyl fluoride (CH3CH2CFO) and 2-methylpropionyl
      fluoride ((CH3)2CHCFO), dissolved in liquid xenon have been recorded. From these
      data, the enthalpy difference has been determined to be 329 +/- 33 cm(-1) (3.94
      +/- 0.39 kJ/mol) for propionyl fluoride with the trans conformer (methyl group
      eclipsing the oxygen atom) more stable than the gauche form. For 2
      methylpropionyl fluoride, the enthalpy difference has been determined to be 297
      +/- 30 cm(-1) (3.55 +/- 0.36 kJ/mol) with the gauche conformer (methyl group
      eclipsing the oxygen atom) more stable than the trans form. From these DeltaH
      values along with assigned torsional fundamentals for both conformers and
      accompanying "hot bands" the potential functions governing the conformational
      interchange have been calculated. Utilizing the infrared data from the xenon
      solution and ab initio frequency predictions from MP2/6-31G* calculations, a few
      reassignments of the fundamentals have been made. Ab initio calculations have
      been carried out with several different basis sets up to MP2/6-311 + G** from
      which structural parameters and conformational stabilities have been determined.
      Additionally, force constants, infrared intensities, Raman activities,
      depolarization ratios, and scaled vibrational frequencies have been determined
      from MP2/6-31G* calculations. Adjusted structural parameters have been obtained
      from combined ab initio predicted values and previously reported microwave data.
      These parameters are compared to those obtained from either the earlier microwave
      and/or electron diffraction studies. Similar ab initio calculations and
      structural parameter determinations have been carried out for acetyl fluoride
      (CH3CFO) and trimethylacetyl fluoride ((CH3)3CCFO) and compared to the
      corresponding experimental results when appropriate.

PMID- 15147691
TI  - Raman spectroscopic analysis of a tembeta: a resin archaeological artefact in
      need of conservation.
AB  - The Raman spectroscopic analysis of a Brazilian tembeta, a lip-plug which
      signifies the attainment of manhood in tribal cultures, and dated to about 1600
      years BP is reported. Tembeta are usually made of wood or stone but this lip-plug
      is very rare in that it is made of resin, which has been severely degraded in the
      burial environment; the brownish-red fragmented remains are in an extremely
      fragile condition and information about the chemical composition was required
      before urgent conservation was undertaken. Raman spectra excited at 1064 nm
      showed the presence of triterpenoid materials in the main body of the artefact,
      and indicated that the red-brown coating was not iron(III) oxide as suspected but
      rather degraded resin. Comparison with contemporary resins has facilitated the
      partial identification of the material in this important artefact as a
      triterpenoid-rich material, which is closely similar to the Pistacia species. A
      possible archaeological link to the Jatoba do Cerrado (Hymenaea stigonocarpa
      Mart.) resin has been excluded as the Raman spectra of this resin specimen and
      the tembeta do not match; indeed, the Jatoba do Cerrado resin specimen belongs to
      a diterpenoid-rich classification as befits its Hymenaea species.

PMID- 15147692
TI  - Effect of n-alkyl chain length on the complexation of phenanthrene and 9-alkyl
      phenanthrene with beta-cyclodextrin.
AB  - The characteristics of host-guest complexation between beta-cyclodextrin (beta
      CD) and phenanthrene derivatives (phenanthrene, n-propyl, n-butyl and n-hexyl
      phenanthrene) were investigated by fluorescence spectrometry. Linear and non
      linear regression methods were used to estimate the formation constants (K1). A
      1:1 stoichiometric ratio and an effect of n-alkyl chain length on the formation
      constant were observed for the binary inclusion complex between guest and beta
      CD. The formation constant dramatically increases with the length of n-alkyl, it
      starts from the value of 140 l mol(-1) for the phenanthrene to reach the value of
      580 l mol(-1) for hexyl-phenanthrene. The effect of the temperature on the
      fluorescence intensity of each complex (guest-host) was also studied; and then
      the thermodynamic parameters were calculated. The main inclusion site seems to be
      aromatic moiety for short chain molecules, and it moves toward the alkyl chain
      part, as the chain becomes longer.

PMID- 15147693
TI  - Interaction between methyl glyoxal and ascorbic acid: experimental and
      theoretical aspects.
AB  - The absorption spectral change of methyl glyoxal (MG) due to the interaction with
      ascorbic acid (AA or Vitamin C) has been investigated using steady-state
      spectroscopic technique. A plausible explanation for the spectral change has been
      discussed on the basis of hydrogen bonding interaction between the two
      interacting species. The equilibrium constant for the complex formation due to
      hydrogen bonding interaction between MG and AA has been obtained from absorption
      spectral changes. Ab inito calculations with DFT B3LYP/6/31G (d,p) basis sets
      have been used to find out the molecular structure of the hydrogen bonded
      complex. The O...H distance found in the O-H...O hydrogen bond turns out to be
      quite short (1.974 A) which is in conformity with the large value of the
      equilibrium constant determined experimentally.

PMID- 15147695
TI  - Raman spectroscopy of benzenesulfonic and 4-toluenesulfonic acids dissolved in
      dimethylsulfoxide.
AB  - Solutions of benzenesulfonic acid (BSA) and 4-toluenesulfonic acid monohydrate
      (PTSA) in dimethylsulfoxide (DMSO) were studied by FT-Raman spectroscopy in the
      concentration range 1.0-3.5 mol dm(-3) (BSA) and 1.0-4.8 mol dm(-3) (PTSA).
      Spectra in the region of the Raman acid complex band (C-S + C-C + SO3) stretches,
      at 1124 cm(-1) were analysed by band-fitting procedures in order to ascertain the
      degree of acid dissociation. In BSA solutions, this parameter changes from 0.78
      at 1.02 M to 0.47 at 3.5M, despite the strong character of the acid. Interaction
      of DMSO with undissociated BSA produces a new band in the solvent nu(C-S) Raman
      spectral region near 671 cm(-1), displaced >15.0 cm(-1), and assigned to DMSO
      molecules H-bonded to BSA. In PTSA solutions, hydrogen bonds are formed with the
      oxonium ion (H3O+) dissociated from the acid. In this case, the displacement
      observed is only >10.0 cm(-1), indicating a weaker interaction. From the
      concentration of H-bonded DMSO, the solute/solvent coordination number and its
      inverse, the mean number of H-bonds participating in bonding with each solvent
      molecule can be calculated. This coordination number changes in BSA solutions in
      bimodal way, passing through a maximum and reaching a limit of 2 in the most
      concentrated solution. This number agrees with that found in the solid solvate
      BSA.2DMSO. In PTSA solutions, the general trend is similar, but low coordination
      numbers are obtained, in agreement with the low acidity of the oxonium ion. The
      bimodal behaviour observed in both acids is explained by the self-associated
      structure of the solvent.

PMID- 15147694
TI  - Coordination sphere vibrations in copper(II), nickel(II) and cobalt(II) complexes
      with 4-imidazoleacetic acid; metal isotope, deuteration, and density functional
      study.
AB  - Low-frequency vibrational spectra of Cu(II), Ni(II) and Co(II) complexes with 4
      imidazoleacetic acid (HIA) are discussed. Metal isotope and deuteration effects
      were measured and used to assign the metal-ligand vibrations. These effects were
      included in density functional calculations carried out for the [Cu(IA)2]
      complex.

PMID- 15147696
TI  - Spectroscopic investigation on the energy transfer process in photosynthetic
      apparatus of cyanobacteria.
AB  - In this work, we employ cyanobacteria, Spirulina platensis, and separate their
      photosynthetic apparatus, phycobilisome (PBS), thylakoid membrane and
      phycobilisome-thylakoid membrane complex. The steady state absorption spectra,
      fluorescence spectra and corresponding deconvoluted spectra and picosecond time
      resolved spectra are used to investigate the energy transfer process in
      phycobilisome-thylakoid membrane complex. The results on steady state spectra
      show chlorophylls of the photosystem II are able to transfer excitation energy to
      phycobilisome with Chla molecules selectively excited. The decomposition of the
      steady state spectra further suggest the uphill energy transfer originate from
      chlorophylls of photosystem II to cores of phycobilisome, while rods and cores of
      phycobilisome cannot receive energy from the chlorophylls of photosystem I. The
      time constant for the back energy transfer process is 18 ps.

PMID- 15147697
TI  - Molecular relaxation processes in the salt systems containing anions of various
      configurations.
AB  - We present in this paper a comparative analysis of the spectral and molecular
      relaxation parameters of the ionic salts in the region of solid-liquid phase
      transition and in the molten state depending on the anion symmetry (thiocyanate
      (SCN-), a linear rotor, C(infinity v); nitrate (NO3-), a symmetrical top, D3h;
      and perrhenate (ReO4-), a spherical top, Td), size and charge of the cation, and
      temperature. We also present new results of the investigations on molecular
      relaxation in thiocyanate ion in several crown-etheric complexes.

PMID- 15147698
TI  - Vibrational spectroscopy investigation and density functional theory calculations
      on N-benzoylhydrazine ligand and the corresponding uranyl complex.
AB  - Infrared spectra of N-benzoylhydrazine (BHZ) phCONHNH2 and its uranyl complex
      have been studied in the 4000-50 cm(-1) frequency range. Complete equilibrium
      geometry of the ligand molecule have been determined by DFT and BLYP/6-31G* force
      field calculations. Theoretical calculations reveal the existence of a keto
      tautomer. No enol form is present in the molecule in the solid. A complete
      vibrational assignment of the solid state IR and Raman spectra of BHZ was
      performed on the basis of normal coordinate analysis of a single molecule. The
      coordination of oxygen and nitrogen centers of BHZ to UO2(II) has been confirmed
      by study of the IR spectra of UO2 (phCONHNH2)2 complexes.

PMID- 15147699
TI  - EPR and electronic spectral studies on Co(II), Ni(II) and Cu(II) complexes with a
      new tetradentate [N4] macrocyclic ligand and their biological activity.
AB  - Cobalt(II), nickel(II) and copper(II) complexes having the general composition
      M(L)X2 (where M = CO(II), Ni(II) and Cu(II), L = ligand, i.e. 3,4,12,13-tetraketo
      2,5,11,14,19,20-hexaazatricyclo[13.3.1.1(6-10)]cosane; 1(19),6,8,10(20),15,17
      hexaene and X stands for Cl-; NO3- and SO42-), have been prepared. The structure
      of the complexes has been elucidated by elemental analysis, molar conductance,
      magnetic susceptibility measurements, mass, IR, electronic and EPR spectral
      studies. The magnetic moment measurements of the complexes indicate that the
      metal ion is in high-spin state. On the basis of IR, electronic and EPR spectral
      studies an octahedral geometry was assigned for Co(II) and Ni(II) complexes
      whereas tetragonal geometry for Cu(II) complexes. This ligand and its complexes
      were also screened against bacteria and pathogenic fungi in vitro.

PMID- 15147700
TI  - Study of the protein distribution in the pig lens cross section by Raman
      spectroscopy.
AB  - The distribution of proteins in the cross section of a normal pig lens was
      studied by near-infrared Raman spectroscopy. The Raman spectra were measured in
      the visual and equatorial axes of this cross section and the protein peak
      intensities were determined. It was found that along each axis the protein
      intensities fluctuate. They have a considerable increment along the visual axis
      with the exception of the C-N bond peak intensities at 1087.2 cm(-1), which
      decrease, and along the equatorial axis the increment is slight. This increment
      in protein distribution along the visual axis is related with the refractive
      gradient of the lens. The classification of pig lens spectra in these axes was
      performed using principal component analysis (PCA) and linear discriminant
      analysis (LDA). Cross-validation shows an excellent group separation.

PMID- 15147701
TI  - Spectroscopic studies on charge-transfer complexes formed in the reaction of
      ferric(III) acetylacetonate with sigma- and pi-acceptors.
AB  - The reaction of ferric(III) acetylacetonate (donor), Fe(acac)3, with iodine as a
      sigma-acceptor and with other different pi-acceptors have been studied
      spectrophotometrically at room temperature in chloroform. The pi-acceptors used
      in this investigation are 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), p
      chloranil and 7,7',8,8'-tetracyanoquinodimethane (TCNQ). The results indicate the
      formation of 1:1 charge-transfer complexes with a general formula, [Fe(acac)3
      (acceptors)]. The iodine complex was shown to contain the triiodide species,
      [Fe(acac)3]2I(+)I3-, based on the electronic absorptions as well as on the Far
      infrared absorption bands characteristic for the non-linear triiodide species, I3
      , with C2v symmetry. The proposed structure of this complex is further supported
      by thermal and middle infrared measurements.

PMID- 15147702
TI  - Study on the second-order optical behavior of 4-(substituted-benzylidene)-2
      phenyl-4H-oxazol-5-one.
AB  - The maximum absorption wavelengths (lambda(a-max)), absorption coefficient
      (epsilon), maximum emission wavelengths (lambda(e-max)) of 4-benzo[1,3]dioxol-5
      ylmethylene-2-phenyl-4H-oxazol-5-one (1), 4-(3,4-dimethoxybenzylidene)-2-phenyl
      4H-oxazol-5-one (2) and 4-(3,4,5-trimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one
      (3) were measured, their second-order nonlinear polarization values (beta(xxx))
      were determined by solvatochromic method. Although the spectral nature (lambda(a
      max), epsilon, lambda(e-max)) and beta(xxx) values of 1, 2 and 3 were close to
      each other in the same solvent, the second-order harmonic generation (SHG) value
      of sample 1 is higher obviously than that of sample 2 or 3 in solid state. The
      crystal structures of 1 and 2 characterized by single crystal X-ray diffraction
      technique indicated the reason why the SHG value of 1 is higher.

PMID- 15147703
TI  - Molecular magnetic properties of two-copper(II) containing complexes [Cu(II) (1
      phenylamidino-O-n-butylurea) en (H2O)]2(2+) and [Cu(II) sulphato-mono (1
      phenylamidino-O-methylurea)]2. An EPR study.
AB  - Electron paramagnetic resonance (EPR) investigations were conducted on [Cu(II) (1
      phenylamidino-O-n-butylurea) en (H2O)]2(2+) (1) and [Cu(II) sulphato-mono (1
      phenylamidino-O-methylurea)]2 (2) respectively, in the temperature range 300-77K.
      Fine structure characteristics of S = 1 system, was observed in both complexes
      with zero field splitting of 0.0525 and 0.0225 cm(-1), respectively, suggesting
      the formation of dimeric complexes. The presence of the half-field signal
      (DeltaMs= +/-2), in the complex 1, further confirmed the formation of dimer. The
      temperature dependence of EPR signal intensity has given evidence for the
      ferromagnetic (FM) coupling between the two Cu2+ ions. The isotropic exchange
      interaction constants J, were evaluated from this and were found out to be
      approximately 57 and approximately 27 cm(-1), respectively, for the complexes 1
      and 2. The photoacoustic spectra of these complexes had shown a band around
      26,400 cm(-1) characteristic of metal-metal bonding giving an independent support
      for the existence of dimeric Cu2+ species. The high magnetic moment values at
      room temperature for complex 1 (2.68 microB) and complex 2 (2.00 microB),
      obtained from the magnetic susceptibility measurements, support the formation of
      ferromagnetically coupled Cu2+ dimers.

PMID- 15147704
TI  - The dielectric model function. An evidence for the nu3(SO4-) phonon mixing in
      gypsum using polarized IR specular reflectance spectroscopy.
AB  - A complete investigation of the phonon mixing in the nu3(SO4(2-)) frequency
      region was made, under experimental geometry where the reflecting crystal plane
      and the plane of incidence contain two principal dielectric axes. It was shown
      that although it is monoclinic, in the frequency region under inspection, gypsum
      could be treated as an orthorhombic crystal. More sophisticated model dielectric
      functions were introduced for the explanation of the Evans holes in the
      reflectance spectra. Using the model dielectric function, an appearance of the
      shoulder at the higher frequency part of the reflectance band was explained in
      terms of longitudinal and quasilongitudinal phonons. A possibility for Evans type
      interaction was encountered between the nu3(SO4(2-)) Au symmetry type mode and
      probably some of the combination modes.

PMID- 15147705
TI  - Solid state effects in the IR spectrum of octahydridosilasesquioxane.
AB  - Infrared spectrum of Octahydridosilasesquioxane, in the solid state, is reported
      and analyzed to show the presence of significant solid state effects. This is in
      marked contrast with the reported Raman spectroscopic studies of this compound in
      the solid state where no evidence for such a proliferation of these effects were
      found. It is found that the normal modes with radial motion of the atoms in their
      normal coordinate are distinguishable from other vibrations by the distinct
      correlations between the band intensity and the solid state splitting observed in
      the IR spectrum. This new insight suggests an interchange of the literature
      assignments of the two modes nu27 and nu29 in the IR spectrum and a different
      origin to the doublet of bands in the Raman spectrum at 883 and 897 cm(-1).

PMID- 15147706
TI  - Studies on the photodegradation of Rhodamine dyes on nanometer-sized zinc oxide.
AB  - The nanometer-sized ZnO was prepared through the sol-gel method. Its average
      particle diameter, determined by TEM, was 20-30 nm. The specific surface area was
      determined to be 22 m2 g(-1) by BET. The photodegradation mechanism of Rhodamine
      dyes on nanometer-sized ZnO was studied by dynamic molecular spectra, and the
      results showed that the photodegradation of Rhodamine dyes obeyed the rules of a
      pseudo first-order kinetic reaction. The rate constant k of the degradation of
      Rhodamine B (RB) and butyl-Rhodamine (BR) were 0.0128 and 0.0154 min(-1),
      respectively, and the half period t(1/2) were 60 and 52 min, respectively. The
      photodegradation reaction conditions were optimized. After intermixing with
      silver, the photodegradation efficiency was greatly improved. A life-span test
      showed that nanometer-sized ZnO had a long life-span.

PMID- 15147707
TI  - Stability analysis of the two rotational isomers of meta-fluorobenzaldehyde in
      the S0, S1, and S2 electronic states.
AB  - For a determination of the stabilization energy between the two rotational
      isomers of m-fluorobenzaldehyde, the S(1,2)<--S0 absorption spectra were observed
      in fluid n-hexane solutions at 293 and 198 K. After employing a simulation method
      for the spectra, we succeeded in determining the stabilization energies in the
      ground and the relevant excited state at the same time. The energy was estimated
      to be 1.7 +/- 0.5 kJ mol(-1) for S0 and also for S1 while it was 2.9 +/- 0.5 kJ
      mol(-1) for S2. Ab initio calculations at MP2/6-311G** computational level
      predicted that the O-cis form in the S0 state is more stable by 1.9 +/- 0.5 kJ
      mol(-1) than the counterpart rotamer, O-trans form. In summary, a schematic
      energy level diagram of the two rotational isomers will be illustrated for the
      S0, S1, and S2 states in the fluid system.

PMID- 15147708
TI  - Frequency doubling scattering and second-order scattering spectra of phosphato
      molybdate heteropoly acid-protein system and their analytical application.
AB  - In the sulfuric acid medium, the reaction of heteropoly compounds with proteins
      could result in the enhancement of frequency doubling scattering (FDS) and second
      order scattering (SOS). Based on the characteristic, a novel method for the
      determination of trace amounts of protein by using the FDS and SOS method has
      been developed. Their maximum scattering wavelengths, lambda(ex)/lambda(em),
      appear at 940/470 nm for FDS and 350/700 nm for SOS, respectively. In a certain
      range, the concentration of proteins is directly proportional to the enhanced
      intensity of FDS and SOS. The suitable reaction conditions, affecting factors as
      well as the influence of some coexisiting substances were investigated. The
      methods exhibited high sensitivity, and the detection limits were in the range of
      8.6-39.3 ng ml(-1) depending on different methods. The method had good
      selectivity, and was applied to the determination of protein in synthetic samples
      and practical samples with satisfactory results.

PMID- 15147709
TI  - An NMR study of merocyanine-type dyes derived from barbituric acid.
AB  - The 13C NMR of two solvatochromic dyes derived from a barbituric acid acceptor
      and dimethylaminophenyl donor fragments, compound 1 and the related merocyanine
      2, were recorded in various solvents. The observed chemical-shift variations were
      used to interpret their structural differences and solvatochromic behavior in
      solution.

PMID- 15147710
TI  - Study of a reaction between 2,3-dichloro-1,4-naphthoquinone and N,N'-diphenyl
      thiourea involving an EDA adduct as intermediate.
AB  - The reaction between 2,3-dichloro-1,4-naphthoquinone and N,N'-diphenyl thiourea
      in acetonitrile medium, which yields the product, 2,3-(N,N'-diphenylthioureylene)
      naphtho-1,4-quinone has been found to take place in two ways--thermal and
      photochemical. The thermal (dark) reaction occurs through an electron donor
      acceptor (EDA) adduct as intermediate with evolution of HCl and kinetic data fit
      into the scheme A + B<==>AB(fast)-->product(slow) Formation constant of the EDA
      adduct and the rate constant of the slow process have been determined at four
      different temperatures from which the enthalpy of formation of AB has been
      determined. The photochemical reaction has been studied with 360 nm ordinary
      light and also with 365 and 370 nm laser beams. Use of laser causes about 10(3)
      fold increase in the rate of the reaction but does not affect the quantum yield.
      The final product has been isolated and characterised by elemental analysis, 1H
      and 13C NMR, IR spectroscopy and mass spectrometry.

PMID- 15147711
TI  - Fourier-transform infrared and Raman difference spectroscopy studies of the
      phosphorus-containing dendrimers.
AB  - FT IR and Raman spectra of 12 generations of the phosphorus-containing starburst
      dendrimers containing P=S and P=O bonds with terminal aldehyde and P-Cl groups
      were compared. The influence of the encirclement on the band frequencies and
      intensity is studied and due to the predictable, controlled and reproducible
      structure of the dendrimers the information usually inaccessible is obtained.
      Bands in the IR difference (G2'(P=O)-G2'(P=S)) spectra have characteristic EPR
      like form. The strong band at 1600 cm(-1) show marked changes of the optical
      density in dependence of the aldehyde (-CH=O) or azomethyne (-CH=N-) substituents
      in the aromatic ring. The analysis of difference spectra enables one to assign
      the characteristic bands nu(P=S) and nu(P=O) for the bonds in the core, in the
      repeating unit and in the terminal groups of the dendrimers. This assignment is
      supported by the calculation of the absorption curves of the different fragments
      of dendrimer with the force constants and electro-optical parameters. The IR and
      Raman spectra of dendrimers are depended on the ratio of number terminal groups
      to a number of repeating units, which in its turn is strictly determined by the
      generation number. Thus, the marked differences in the vibrational spectra of the
      first successive generations aspire to zero for the higher ones. The rather rigid
      repeated units with little conformational flexibility define the perfect
      microstructure of the studied phosphorus-containing dendrimers up to the eleventh
      generation.

PMID- 15147712
TI  - Conformational stability from variable temperature infrared spectra of krypton
      solutions, ab initio calculations, vibrational assignment, and r0 structural
      parameters of 1,3-difluoropropane.
AB  - The infrared spectra (3200-400 cm(-1)) of krypton solutions of 1,3
      difluoropropane, FCH2CH2CH2F, at variable temperatures (-105 to -150 degrees C)
      have been recorded. Additionally, the infrared spectra (3200-50 cm(-1)) of the
      gas and solid have been recorded as well as the Raman spectrum of the liquid.
      From a comparison of the spectra of the fluid phases with that in the solid, all
      of the fundamental vibrations of the C2 conformer (gauche-gauche) where the first
      gauche indicates the form for one of the CH2F groups and the second gauche the
      other CH2F, and many of those for the C1 form (trans-gauche) have been
      identified. Tentative assignments have been made for a few of the fundamentals of
      the other two conformers, i.e. C2v (trans-trans) and Cs (gauche-gauche'). By
      utilizing six pairs of fundamentals for these two conformers in the krypton
      solutions, an enthalpy difference of 277 +/- 28 cm(-1) (3.31 +/- 0.33 kJ mol(-1))
      has been obtained for the C2 versus C1 conformer with the C2 conformer the more
      stable form. For the C2v conformer, the enthalpy difference has been determined
      to be 716 +/- 72 cm(-1) (8.57 +/- 0.86 kJ mol(-1)) and for the Cs form 971 +/-
      115 cm(-1) (11.6 +/- 1.4 kJ mol(-1)). It is estimated that there is 64 +/- 3% of
      the C2 form, 34 +/-3% of the C1 form, 1% of the C2v form and 0.6% of the Cs
      conformer present at ambient temperature. Equilibrium geometries and total
      energies of the four stable conformers have been determined from ab initio
      calculations with full electron correlation by the perturbation method to second
      order as well as by hybrid density functional theory calculations with the B3LYP
      method using a number of basis sets. The MP2 calculations predict the C1
      conformer stability to be slightly higher than the experimentally determined
      value whereas for the C2v and Cs conformers the predicted energy difference is
      much larger than the experimental value. The B3LYP calculations predict a better
      energy difference for both the C1 and C2v as well as for the Cs conformers than
      the MP2 values. A complete vibrational assignment is proposed for the C2
      conformer and many of the fundamentals have been identified for the C1 form based
      on the force constants, relative intensities and rotational-vibrational band
      contours obtained from the predicted equilibrium geometry parameters. By
      combining previously reported rotational constants for the C2 and C1 conformers
      with ab initio MP2/6-311 + G(d, p) predicted parameters, adjusted r0 parameters
      have been obtained for both conformers. Comparisons are made with the parameters
      obtained for some other molecules containing the FCH2 group. The spectroscopic
      and theoretical results are compared to the corresponding properties for some
      similar molecules.

PMID- 15147713
TI  - Estimations of excited state dipole moments of conformers in some o-substituted
      acetophenones by solvato-chromic shifts.
AB  - Ultra violet absorption spectra of o-methylacetophenone, o-fluoroacetophenone and
      o-hydroxyacetophenone solutions in different solvents are recorded in the region
      200-350 nm at room temperature. Excited state dipole moments for three (pi* <--
      pi) transitions of the benzene ring for solutions in non-polar and polar solvents
      are estimated using solvato-chromic shift method [Delta nu against f(epsilon,
      n)]. The results show that two types of shifts are observed red and blue shifts.
      The dipole moment values obtained on excitation by red shifted bands in non-polar
      solvents are much higher than their counterparts both in the ground state and
      those of the solutions in polar solvents. Those obtained on excitation by blue
      shifted bands have lower values than ground state, some with same direction and
      others of reverse direction in both non-polar and polar solvents.

PMID- 15147714
TI  - Odontoblasts: the cells forming and maintaining dentine.
AB  - Odontoblasts are tall columnar cells located at the periphery of the dental pulp.
      They derive from ectomesenchymal cells originated by migration of neural crest
      cells during the early craniofacial development. Odontoblasts form the dentine, a
      collagen-based mineralized tissue, through secretion of its collagenous and
      noncollagenous organic matrix components and by control the mineralization
      process. A conspicuous cell process arises from the cell body of odontoblasts and
      penetrates into the mineralized dentine. After dentinogenesis, odontoblasts
      deposit new layers of dentine throughout life and might also form a type of
      reactionary/reparative dentine in response to dental caries and other external
      factors may affect teeth.

PMID- 15147715
TI  - Myeloid cells.
AB  - Granulocytes and monocytes, collectively called myeloid cells, are differentiated
      descendants from common progenitors derived from hematopoietic stem cells in the
      bone marrow. Commitment to either lineage of myeloid cells is controlled by
      distinct transcription factors followed by terminal differentiation in response
      to specific colony-stimulating factors and release into the circulation. Upon
      pathogen invasion, myeloid cells are rapidly recruited into local tissues via
      various chemokine receptors, where they are activated for phagocytosis as well as
      secretion of inflammatory cytokines, thereby playing major roles in innate
      immunity. Genetic alterations in myeloid cells may cause an abnormal increase in
      mature myeloid or blast cells resulting in chronic or acute myelogenous leukemia.

PMID- 15147716
TI  - Measles: immune suppression and immune responses.
AB  - Measles is a highly contagious viral disease that remains the leading vaccine
      preventable cause of child mortality worldwide. Deaths from measles are due
      largely to an increased susceptibility to secondary bacterial and viral
      infections, attributed to a prolonged state of immune suppression. Several
      abnormalities of the immune system have been described, including changes in
      lymphocyte number and function, shifts in cytokine responses, immunomodulatory
      effects of interleukin-10, down regulation of interleukin-12, impaired antigen
      presentation, and altered interferon alpha/beta signaling pathways. Although the
      current vaccine is very effective, knowledge of the molecular basis of the immune
      responses to measles virus could contribute to the development of a safer, more
      immunogenic measles vaccine. However, the safety of new measles vaccines must be
      carefully investigated, as two measles vaccines have resulted in unintended
      immunologic consequences: atypical measles following administration of the
      formalin-inactivated measles vaccine and increased mortality in girls following
      administration of high-titer measles vaccines.

PMID- 15147717
TI  - Inherited pancreatic cancer: improvements in our understanding of genetics and
      screening.
AB  - Inherited pancreatic cancers represent approximately 5-10% of all pancreatic
      cancers. Pancreatic cancer may be inherited as part of a known cancer syndrome or
      in association with hereditary pancreatitis or cystic fibrosis. However, most
      inherited pancreatic cancers do not occur in the context of a known syndrome, and
      these are referred to as familial pancreatic cancers. Growing evidence suggests
      the presence of a single autosomal dominant gene in familial pancreatic cancer
      kindreds, and a susceptibility locus on chromosome 4 has recently been identified
      in one such family. Pancreatic cancer is believed to arise from pancreatic
      dysplasia, and familial pancreatic cancer kindreds represent a particularly high
      risk population for whom effective screening strategies are needed. One promising
      strategy has used endoscopic ultrasound to detected pancreatic dysplasia in
      members of familial pancreatic cancer kindreds.

PMID- 15147718
TI  - Coagulation factor V.
AB  - The coagulation cascade involves sequential enzymatic activations of serine
      protease zymogens that converge on the generation of thrombin. Factor V (FV)
      takes part in this process as a component of the prothrombinase complex. Besides
      its role as procoagulant factor, it is also involved in the physiologic
      anticoagulant pathway, by participating in the inactivation of activated factor
      VIII (FVIIIa). Given the dual role of FV, genetic defects in FV gene may result
      in opposite hemorrhagic or thrombotic phenotypes. This review focuses on the
      structure, function (procoagulant and anticoagulant), regulation (activation and
      inactivation) of FV as well as on the genetic defects associated with mutations
      in the FV gene.

PMID- 15147719
TI  - Lipofuscin.
AB  - Over time, postmitotic cells accumulate a non-degradable intralysosomal
      substance, lipofuscin, which forms due to iron-catalyzed oxidation/polymerization
      of protein and lipid residues. Lipofuscin is often considered a hallmark of
      aging, showing an accumulation rate that inversely correlates with longevity.
      There is an emerging impression that lipofuscin, although still typically
      considered a harmless wear-and-tear product, may have multiple negative effects.
      By interfering with the important autophagic process, by which most worn out
      cellular components are degraded, it may prevent cellular renewal and advance the
      accumulation of damaged cellular constituents. Due to binding of transition
      metals, such as iron and copper, lipofuscin also seems to sensitize lysosomes and
      cells to oxidative stress. Of importance for the pathogenesis of age-related
      macular degeneration, lipofuscin deposition interferes with the phagocytic
      activity of retinal pigment epithelial cells and also sensitizes their lysosomes
      to blue light.

PMID- 15147720
TI  - The collagen receptor subfamily of the integrins.
AB  - The four collagen receptor integrins, alpha1beta1, alpha2beta1, alpha10beta1 and
      alpha11beta1, form a structurally and functionally distinct subgroup when
      compared to other members of the integrin family. In this review, we discuss the
      structures of these receptors and their differences in collagen binding and
      signalling function.

PMID- 15147721
TI  - Opening the chromatin for transcription.
AB  - Eukaryotic genomes are packaged into a dynamic hierarchy chromatin structure. In
      such a particular context, the transition from a repressed compacted chromatin to
      a rather extended fiber is necessary for transcription. The chromatin opening
      includes three events, the initial factor getting access to nucleosome DNA, local
      chromatin opening mediated by activator/coactivator, and transcription associated
      with extensive chromatin opening. Chromatin dynamics, which is DNA sequence
      dependent, and also occurs in condensed fiber, provides the opportunity for
      activators binding to DNA. Coactivators recruited by the activator open the
      chromatin locally. However, it appears that genes adopt distinct chromatin
      opening mechanisms according to whether the gene is induced expression,
      developmental and tissue-specific expression, or constitutive expression. In
      contrast to transcription initiation-related local chromatin opening, large scale
      of chromatin opening is associated with a functional enhancer as well as high
      transcription rate. How the transcription initiated from an enhancer or enhancer
      like modules, i.e. intergenic transcription, conducts the extensive chromatin
      opening is discussed. A model for long-range interaction that non-coding
      transcripts from enhancers may promote efficient communication with promoters is
      proposed.

PMID- 15147722
TI  - Cyclin E.
AB  - E-type cyclins (cyclin E1 and cyclin E2) are expressed during the late G1 phase
      of the cell cycle until the end of the S-phase. The activity of cyclin E is
      limiting for the passage of cells through the restriction point "R" which marks a
      "point of no return" for cells entering the division cycle from a resting state
      or passing from G1 into S-phase. Expression of cyclin E is regulated on the level
      of gene transcription mainly by members of the E2F trrnscription factor family
      and by its degradation via the proteasome pathway. Cyclin E binds and activates
      the kinase Cdk2 and by phosphorylating its substrates, the so-called "pocket
      proteins", the cyclic/Cdk2 complexes initiate a cascade of events that leads to
      the expression of S-phase specific genes. Aside from this specific function as a
      regulator of S-phase-entry, cyclin E plays a direct role in the initiation of DNA
      replication, the control of genomic stability, and the centrosome cycle.
      Surprisingly, recent studies have shown that the once thought essential cyclin E
      is dispensable for the development of higher eukaryotes and for the mitotic
      division of eukaryotic cells. Nevertheless, high level cyclin E expression has
      been associated with the initiation or progression of different human cancers, in
      particular breast cancer but also leukemia, lymphoma and others. Transgenic mouse
      models in which cyclin E is constitutively expressed develop malignant diseases,
      supporting the notion of cyclin E as a dominant onco-protein.

PMID- 15147723
TI  - Purification and characterization of a new antiviral protein from the leaves of
      Pandanus amaryllifolius (Pandanaceae).
AB  - A lectin, designated Pandanin, was isolated from the saline extract of the leaves
      of Pandanus amaryllifolius, using ammonium sulfate precipitation, affinity
      chromatography on mannose-agarose and molecular size exclusion by gel filtration.
      Pandanin is an unglycosylated protein with a molecular mass of 8.0 kDa both after
      gel filtration and on sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      indicating that it is a single polypeptide chain. The first 10 residues of the N
      terminal amino acid sequence are DNILFSDSTL. An analysis of the sequence of first
      30 amino acids at the N-terminal region shows that Pandanin has about 50-60%
      homology to those of mannose-specific lectins reported from monocot plants.
      Pandanin exhibits hemagglutinating activity toward rabbit erythrocytes, and its
      activity could be reversed exclusively by mannose and mannan. Pandanin also
      possesses antiviral activities against human viruses, herpes simplex virus type-1
      (HSV-1) and influenza virus (H1N1) with 3 day's EC50 of 2.94 and 15.63 microM,
      respectively.

PMID- 15147724
TI  - Modifications of chromatin structure and gene expression following induced
      alterations of cellular shape.
AB  - In higher eukaryotes cellular shape is a dynamic element which can be altered by
      external and internal factors (i.e. surface interactions, temperature, ionic
      strength). Our question was: might modifications of cell shape reflect on nuclear
      morphology and architecture and hence on chromatin function, in order to
      represent a mechanism of cell regulation? We altered the shape of cultured
      fibroblasts by coating the growth substratum with synthetic polymers, which
      alternatively increased and decreased the adhesiveness. By means of Fluorescence
      microscopy we analysed the modifications of cell and nucleus architecture induced
      by the different substrata. Then we used differential scanning calorimetry to
      investigate if a remodelling of chromatin structure was associated with the
      induced morphological changes. Finally, we evaluated if the observed
      modifications of chromatin condensation affect the transcriptional profile. At
      this stage of the work we focused on just four genes (c-myc, c-fos, c-jun and
      collagen) and we analysed their expression by dot blot hybridization and RT-PCR.
      The results confirm that mechanical factors external to the cell, such as the
      physico-chemical features of the substratum, are able to modulate gene
      transcription through a remodelling of chromatin structure. Therefore the work
      supports our starting hypothesis of a regulatory pathway connecting in sequence
      cellular morphomety/nuclear architecture/chromatin structure/gene expression.

PMID- 15147725
TI  - Kupffer cell cytokines interleukin-1beta and interleukin-10 combine to inhibit
      phosphoenolpyruvate carboxykinase and gluconeogenesis in cultured hepatocytes.
AB  - BACKGROUND AND AIMS: Recent evidence suggests that inflammatory cytokines may
      mediate reduced hepatic glucose production and reduced blood glucose
      concentrations in sepsis. Therefore the aim of this study is to provide direct
      evidence of a cytokine-mediated interaction between Kupffer cells and hepatocytes
      by characterising the effects of lipopolysaccharide-stimulated Kupffer cells on
      hepatocyte gluconeogenesis, and the activity of key regulatory enzymes of this
      pathway. METHODS AND RESULTS: Primary isolates of hepatocytes co-cultured with
      lipopolysaccharide-stimulated Kupffer cells in Transwell inserts showed a 48%
      inhibition of gluconeogenesis (P < 0.001). RNase protection assay and ELISA of
      Kupffer cells and the culture media following exposure to lipopolysaccharide
      showed increased levels of interleukin-1 alpha and beta, tumour necrosis factor
      alpha and IL-10. The addition of IL-1beta and IL-10 to hepatocyte cultures
      inhibited gluconeogenesis by 52% (P < 0.001), whereas each cytokine alone was
      ineffective. To determine whether altered production or activity of
      phosphoenolpyruvate carboxykinase or pyruvate kinase was responsible for the
      reduced glucose synthesis, their mRNA, protein levels and enzyme activities were
      measured. Primary hepatocytes co-cultured with lipopolysaccharide-stimulated
      Kupffer cells or cultured with a combination of IL-1beta and IL-10 displayed
      reduced levels of phosphoenolpyruvate carboxykinase mRNA, protein and enzyme
      activity. In contrast the mRNA, protein levels and enzyme activity of pyruvate
      kinase were not altered; suggesting that gluconeogenesis was suppressed by
      downregulation of phosphoenolpyruvate carboxykinase. CONCLUSIONS: Therefore,
      hypoglycaemia, which is often observed in sepsis, may be mediated by Kupffer cell
      derived IL-1beta and IL-10. In addition this study suggests these cytokines
      inhibit phosphoenolpyruvate carboxykinase production and thereby hepatic
      gluconeogenesis.

PMID- 15147726
TI  - Interference effect of epigallocatechin-3-gallate on targets of nuclear factor
      kappaB signal transduction pathways activated by EB virus encoded latent membrane
      protein 1.
AB  - AIM: To elucidate the interference effect of epigallocatechin-3-gallate (EGCG) on
      targets of nuclear factor kappaB (NF-kappaB) signal transduction pathway
      activated by EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal
      carcinoma (NPC) cell lines. METHODS: The survival rates of CNE1 and CNE-LMP1 cell
      lines after the EGCG treatment were determined by MTT assay. NF-kappaB activation
      in CNE1 and CNE-LMP1 cells after EGCG treatment was analyzed by promoter
      luciferase reporter system. And then nuclear translocation of NF-kappaB (p65)
      after the EGCG treatment was analyzed by immunofluorescence and western blotting.
      Meanwhile, the changes of IkappaBalpha phosphorylation were observed after the
      EGCG treatment. EGFR promoter activity was analyzed by promoter luciferase
      reporter system and EGFR phosphorylation was observed by western blotting after
      the EGCG treatment. RESULTS: EGCG inhibited the survival rates of CNE1 and CNE
      LMP1 cells and NF-kappaB activation caused by LMP1 in CNE-LMP1 cells. EGCG also
      suppressed the nuclear translocation of NF-kappaB (p65) and IkappaBalpha
      phosphorylation. Meanwhile, EGCG inhibited EGFR promoter activity and EGFR
      phosphorylation. CONCLUSIONS: EGCG inhibited not only the dose-dependent survival
      rate of NPC cells, but also the dose-dependent activation of NF-kappaB. This
      inhibition of LMP1-caused NF-kappaB activation was mediated via the
      phosphorylative degradation of its inhibitory protein IkappaBalpha, and then EGCG
      inhibited EGFR activity which was a downstream gene from NF-kappaB. This study
      suggests that interference effect of EGCG on targets of signal transduction
      pathway plays an important role in the anticancer function.

PMID- 15147727
TI  - Transforming growth factor-beta1 decreases melanin synthesis via delayed
      extracellular signal-regulated kinase activation.
AB  - Transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in cell
      proliferation, differentiation, and apoptosis. In this study, we investigated the
      effects of TGF-beta1 on melanogenesis using a spontaneously immortalized mouse
      melanocyte cell line, Mel-Ab. Our results show that TGF-beta1 significantly
      inhibits melanin synthesis in a concentration-dependent manner and that it
      reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. We also
      found that TGF-beta1 reduces microphthalmia-associated transcription factor
      (MITF) promoter activity and decreased MITF, tyrosinase, tyrosinase-related
      protein-1 (TRP-1), and TRP-2 protein production. In addition, TGF-beta1 was found
      to induce a delay in the activation of extracellular signal-regulated kinase
      (ERK) at 6h, whereas many growth factors activate ERK transiently in minutes.
      Moreover, the specific ERK pathway inhibitor, PD98059 blocked the hypopigmenting
      effects induced by TGF-beta1. PD98059 was also found to abrogate the TGF-beta1
      mediated down-regulation of MITF, tyrosinase, TRP-1, and TRP-2 production. These
      results suggest that the ERK pathway may be involved in the melanogenic signaling
      cascade, and that delayed ERK activation by TGF-beta1 contributes to reduced
      melanin synthesis via MITF down-regulation.

PMID- 15147729
TI  - An adenosine analog (IB-MECA) inhibits anchorage-dependent cell growth of various
      human breast cancer cell lines.
AB  - A3 adenosine receptor agonists have been reported to influence cell death and
      survival. Here we report the effects of an A3 adenosine receptor agonist, IB
      MECA, on the cell growth of human breast cancer cell lines, MCF-7 (estrogen
      receptor positive) and MDA-MB468 (estrogen receptor negative). Therefore, this
      study was aimed to investigate the expression and possible action of A3 receptor
      in the human breast cancer cell lines. IB-MECA, at 1-100 microM, resulted in a
      significant cell growth inhibition (P < 0.05) which reached the maximum at 48 h,
      in the cell lines. In both cell lines, agonist-induced effects were antagonized
      by pretreatment with a selective A3 adenosine receptor antagonist, MRS1220. Using
      RT-PCR method, further confirmation was provided by the presence of mRNA of A3
      receptor in the cells. In addition, IB-MECA was able to inhibit forskolin
      stimulated cAMP levels, which indicate the functional form of A3 receptor on the
      cell surface of these breast cancer cell lines. These results suggest that the
      inhibitory effect of IB-MECA on the growth of human breast cancer cell lines is
      mediated through activation of A3 adenosine receptor.

PMID- 15147728
TI  - Molecular cloning and characterization of chemokine-like factor super family
      member 1 (CKLFSF1), a novel human gene with at least 23 alternative splicing
      isoforms in testis tissue.
AB  - Chemokine-like factor (CKLF) was isolated from PHA-stimulated U937 cells. It is
      composed of 152 amino acids and located on chromosome 16q22. Utilizing
      bioinformatics, based on CKLF cDNA and protein sequences, in combination with
      experimental validation, we identified a novel gene designated chemokine-like
      factor super family member 1 (CKLFSF1). CKLFSF1 maps on chromosome 16q22, and the
      full-length gene comprises of seven exons and six introns. Using RACE-PCR, we
      identified two potential alternative transcription start sites, 1A and 1B.
      Northern blot and RT-PCR analysis demonstrated that CKLFSF1 is predominantly
      expressed in human testis tissue, with only lower levels of expression in many
      other human tissues. RT-PCR and cDNA sequencing identified 23 alternatively
      spliced isoforms of CKLFSF1 in the testis tissue, which encode protein variants
      ranging from 36 to 169 amino acids in length. Immunohistochemistry analysis
      demonstrated that CKLFSF1 proteins are highly expressed in spermatocyte and in
      tissue fluid of human testes tissue. In light of these findings, we propose that
      CKLFSF1 may play an important role in spermatogenesis or testicular development.

PMID- 15147730
TI  - Enzyme-to-enzyme channelling in the early steps of glycolysis in rat pancreatic
      islets.
AB  - The metabolism of D-glucose displays anomeric specificity in rat pancreatic
      islets. The aim of the present report is to investigate whether such a situation
      implies enzyme-to-enzyme tunnelling of metabolites in the early steps of
      glycolysis. For such a purpose, the modelling of alpha- and beta-D-glucose
      catabolism, itself based on available information concerning both the utilisation
      of these two anomers and the intrinsic properties of phosphoglucoisomerase, was
      first examined. According to a theoretical model with enzyme-to-enzyme
      channelling, the generation of 3HOH from D-[2-3H]glucose should be higher in
      islets exposed to beta-D-glucose rather than alpha-D-glucose, whilst the opposite
      situation should prevail in the case of D-[5-3H]glucose conversion to 3HOH.
      Experimental data collected in rat islets incubated for 60 min at 4 degrees C in
      the presence of either alpha- or beta-D-glucose mixed with tracer amounts of
      either alpha- or beta-D-[2- 3H]glucose and alpha- or beta-D-[5-3H]glucose
      indicate that the beta/alpha ratio for D-[2-3H]glucose conversion to 3HOH is
      indeed higher than the beta/alpha ratio for D-[5-3H]glucose conversion to 3HOH.
      These findings are consistent with the postulated enzyme-to-enzyme tunnelling of
      glycolytic intermediates between hexokinase isoenzyme(s), phosphoglucoisomerase
      and, possibly, phosphofructokinase.

PMID- 15147732
TI  - Porcine spermatozoa contain more than one membrane progesterone receptor.
AB  - Progesterone has been shown to be a physiologically relevant inducer of the sperm
      acrosome reaction. A novel protein intrinsic to microsomal membranes, membrane
      progesterone receptor (mPR, now termed progesterone membrane receptor component
      1, PGMRC1) that binds progesterone with high affinity has been cloned from
      porcine liver previously, and corresponding antibodies mitigate the progesterone
      induced acrosome reaction. In this study we aimed at the localization of mPR in
      porcine spermatozoa. Immunostaining suggested the exclusive occurrence of mPR in
      a hardly accessible place, possibly the inner acrosomal membrane, with digitonin
      dramatically increasing the number of positively stained cells. Consistent with
      the structure prediction for mPR, its short N-terminus (NT) but not the large C
      terminal part becomes accessible from outside after digitonin treatment as
      evidenced by the staining pattern of antibodies directed against different
      regions of the protein. However, digitonin treatment solubilizes a progesterone
      binding activity of approximately 140 kDa molecular weight, that is different
      from mPR, which remains in the cell membrane as demonstrated by Western blotting.
      Ligand binding studies confirm the dissimilarity of mPR and the digitonin-soluble
      progesterone binding protein. Chemical modification studies also indicate that
      the digitonin-soluble progesterone binding protein has a binding site that
      differs from that of mPR. It is concluded that more than one progesterone
      receptor is present in porcine spermatozoa.

PMID- 15147731
TI  - Reticulon 4 in chondrocytic cells: barosensitivity and intracellular
      localization.
AB  - Members of the reticulon gene family are endoplasmic reticulum (ER)-related
      proteins expressed in various human tissues, but their molecular functions are
      not understood. The reticulon 4 subfamily consists of three members, reticulon
      4/Nogo-A, -B and -C. Reticulon 4-A is under intense investigation because of its
      inhibitory effect on neurite outgrowth, and reticulon 4-B has been suggested to
      induce apoptosis. Reticulon 4-C, the shortest member of this subfamily, is the
      least characterized. Reticulons are presumably guided to endoplasmic reticulum by
      a putative N-terminal retention motif. In this study the expressions of reticulon
      4 subtypes in human chondrosarcoma cell line and in primary bovine chondrocytes
      were analyzed on mRNA level. These cell types, exposed to strong mechanical
      forces in vivo, were subjected to high hydrostatic pressure and mechanical
      stretch to study the possible mechanosensitivity of reticulon 4 genes. In
      addition, a green fluorescent protein-tagged reticulon 4-C and a fusion protein
      with mutated endoplasmic reticulum retention signal were used to study the
      significance of the C-terminal translocation signal (the di-lysine motif). As the
      result, both cell types expressed the three main isoforms of reticulon 4 family.
      The steady-state level of reticulon 4-B mRNA was shown to be up-regulated by
      pressure, but not by mechanical stretch indicating transcriptional
      barosensitivity. The reticular distribution pattern of reticulon 4-C was observed
      indicating a close association with endoplasmic reticulum. Interestingly, this
      pattern was maintained despite of the disruption of the putative localization
      signal. This suggests the presence of another, yet unidentified endoplasmic
      reticulum retention mechanism.

PMID- 15147733
TI  - Molecular cloning and characterization of a novel dual-specificity phosphatase 23
      gene from human fetal brain.
AB  - Most of dual-specificity protein phosphatases (DSPs) play an important role in
      the regulation of mitogenic signal transduction and controlling the cell cycle in
      response to extracellular stimuli. In this study, a novel human dual-specificity
      protein phosphatases gene named dual-specificity phosphatase 23 (DUSP23) was
      isolated by large-scale sequencing analysis of a human fetal brain cDNA library.
      Its cDNA was 726 bp in length, encoding a 150-amino acid polypeptide which
      contained a dual-specificity phosphatase catalytic (DSPc) domain but not a CDC25
      homology (CH2) domain. Reverse transcription-PCR (RT-PCR) revealed that the
      DUSP23 was expressed in most fetal tissues and two adult tissues: testis and
      colon. Transient transfection experiment suggested that DUSP23 was localized in
      the cytoplasm of HEK293 cells. DUSP23 showed distinctive phosphatase activity
      toward p-nitrophenyl phosphate (pNPP), as well as oligopeptides containing
      phospho-tyrosine and phospho-threonine residues. Furthermore, DUSP23 could
      dephosphorylate p44ERK1 but not p38 and p54SAPKbeta in vitro. All the results
      indicated that DUSP23 was a novel protein phosphatase with dual substrate
      specificity.

PMID- 15147734
TI  - Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell
      apoptosis.
AB  - Bim proteins are essential factors of apoptosis. Nine isoforms of Bim have been
      submitted to GenBank database. In order to improve the understanding of the
      regulation of Bims' proapoptotic activity, we screened a multiple tissue cDNA
      panels for Bim isoforms and tested their proapoptotic activity by over
      expression. Two novel cDNA isoforms of Bim family are generated by alternative
      splicing. One isoform encodes a 79 residue putative protein with a BH3 domain,
      named Bim alpha3. There is not any significant ORF found in another isoform,
      named Bim beta5. Subcellular localized analysis of EGFP-Bim fusion protein
      suggests Bim alpha3 distributed to both plasma and nucleus of HEK 293 cell. HEK
      293 cells transfected with pcDNA-Bim alpha3 presented a similar proapoptotic
      activity (32.05 +/- 6.42%) with Bim alpha2 (30.14 +/- 2.66%). The proapoptotic
      activity of Bim alpha3 was obviously weaker than that of Bim S (46.52 +/- 5.07%)
      and Bim L (55.53 +/- 1.99%). Anti-sense over-expression of Bim in HEK 293 cells
      results in a weak down-regulated proapoptotic level. Expression pattern analysis
      reveals that both the novel cDNAs are expressed widely in normal tissue just like
      the other reported isoforms. The expression pattern of Bim isoforms shows tissue
      specific obviously. The results suggest that BH3 domain is sufficiency for
      proapoptotic activity of Bim proteins. The functional state of Bims might be
      regulated both in the transcript and post transcript process.

PMID- 15147735
TI  - The association of calmodulin with central spindle regulates the initiation of
      cytokinesis in HeLa cells.
AB  - Calmodulin is a major cytoplasmic calcium receptor that performs multiple
      functions in the cell including cytokinesis. Central spindle appears between
      separating chromatin masses after metaphase-anaphase transition. The interaction
      of microtubules from central spindle with cell cortex regulates the cleavage
      furrow formation. In this paper, we use green fluorescence protein (GFP)-tagged
      calmodulin as a living cell probe to examine the detailed dynamic redistribution
      and co-localization of calmodulin with central spindle during cytokinesis and the
      function of this distribution pattern in a tripolar HeLa cell model. We found
      that calmodulin is associated with spindle microtubules during mitosis and begins
      to aggregate with central spindle after anaphase initiation. The absence of
      either central spindle or central spindle-distributed calmodulin is correlated
      with the defect in the formation of cleavage furrow, where contractile ring
      distributed CaM is also extinct. Further analysis found that both the assembly of
      central spindle and the formation of cleavage furrow are affected by the W7
      treatment. The microtubule density of central spindle was decreased after the
      treatment. Only less than 10% of the synchronized cells enter cytokinesis when
      treated with 25 microM W7, and the completion time of furrow regression is also
      delayed from 10 min to at least 40 min. It is suggested that calmodulin plays a
      significant role in cytokinesis including furrow formation and regression, The
      understanding of the interaction between calmodulin and microtubules may give us
      insight into the mechanism through which calmodulin regulates cytokinesis.

PMID- 15147736
TI  - Lung fibroblast clones from normal and fibrotic subjects differ in hyaluronan and
      decorin production and rate of proliferation.
AB  - Development of fibrosis involves an increase in the deposition of connective
      tissue components including collagens, fibronectin and proteoglycans. One
      hypothesis to account for matrix deposition in fibrosis is that fibroblast with
      differing matrix producing capacity are involved in the fibrotic process. To test
      this hypothesis, primary fibroblast cultures and clones derived from these
      primary lines were established from the lung tissue of control patients and
      patients with pulmonary fibrosis. The primary lines and derived clones were
      studied in relation to their capacity to proliferate and to produce proteoglycans
      and hyaluronan. Primary fibroblast cultures and clones from normal subjects and
      patients with lung fibrosis differed considerably, with up to 13-fold difference,
      in both hyaluronan and proteoglycan production. The major proteoglycan produced
      was decorin in both controls and cultures from fibrotic patients, while cultures
      from patients with lung fibrosis had a higher expression of mRNA for both
      collagen and decorin. Clones derived from a primary line from a fibrotic patient
      secreted 3-fold greater amounts of decorin than those from a control subject.
      Furthermore, a negative correlation between proliferation and synthesis of
      decorin was noted. We suggest that different fibroblast clones accumulate in the
      lung, and that specific cell populations of high decorin producing fibroblasts
      may exist which are crucial in the pathogenesis of fibrosis.

PMID- 15147737
TI  - A Trypanosoma cruzi heat shock protein 40 is able to stimulate the adenosine
      triphosphate hydrolysis activity of heat shock protein 70 and can substitute for
      a yeast heat shock protein 40.
AB  - The process of assisted protein folding, characteristic of members of the heat
      shock protein 70 (Hsp70) and heat shock protein 40 (Hsp40) molecular chaperone
      families, is important for maintaining the structural integrity of cellular
      protein machinery under normal and stressful conditions. Hsp70 and Hsp40
      cooperate to bind non-native protein conformations in a process of adenosine
      triphosphate (ATP)-regulated assisted protein folding. We have analysed the
      molecular chaperone activity of the cytoplasmic inducible Hsp70 from Trypanosoma
      cruzi (TcHsp70) and its interactions with its potential partner Hsp40s (T. cruzi
      DnaJ protein 1 [Tcj1] and T. cruzi DnaJ protein 2 [Tcj2]). Histidine-tagged
      TcHsp70 (His-TcHsp70), Tcj1 (Tcj1-His) and Tcj2 (His-Tcj2) were over-produced in
      Escherichia coli and purified by nickel affinity chromatography. The in vitro
      basal specific ATP hydrolysis activity (ATPase activity) of His-TcHsp70 was
      determined as 40 nmol phosphate/min/mg protein, significantly higher than that
      reported for other Hsp70s. The basal specific ATPase activity was stimulated to a
      maximal level of 60 nmol phosphate/min/mg protein in the presence of His-Tcj2 and
      a model substrate, reduced carboxymethylated alpha-lactalbumin. In vivo
      complementation assays showed that Tcj2 was able to overcome the temperature
      sensitivity of the ydj1 mutant Saccharomyces cerevisiae strain JJ160, suggesting
      that Tcj2 may be functionally equivalent to the yeast Hsp40 homologue (yeast DnaJ
      protein 1, Ydj1). These data suggest that Tcj2 is involved in cytoprotection in a
      similar fashion to Ydj1, and that TcHsp70 and Tcj2 may interact in a nucleotide
      regulated process of chaperone-assisted protein folding.

PMID- 15147738
TI  - CLIC-2 modulates cardiac ryanodine receptor Ca2+ release channels.
AB  - We have examined the biochemical and functional properties of the recently
      identified, uncharacterised CLIC-2 protein. Sequence alignments showed that CLIC
      2 has a high degree of sequence similarity with CLIC-1 and some similarity to the
      omega class of glutathione transferases (GSTO). A homology model of CLIC-2 based
      on the crystal structure of CLIC-1 suggests that CLIC-2 belongs to the GST
      structural family but, unlike the GSTs, CLIC-2 exists as a monomer. It also has
      an unusual enzyme activity profile. While the CXXC active site motif is conserved
      between CLIC-2 and the glutaredoxins, no thiol transferase activity was detected.
      In contrast, low glutathione peroxidase activity was recorded. CLIC-2 was found
      to be widely distributed in tissues including heart and skeletal muscle.
      Functional studies showed that CLIC-2 inhibited cardiac ryanodine receptor Ca2+
      release channels in lipid bilayers when added to the cytoplasmic side of the
      channels and inhibited Ca2+ release from cardiac sarcoplasmic reticulum vesicles.
      The inhibition of RyR channels was reversed by removing CLIC-2 from the solution
      or by adding an anti-CLIC-2 antibody. The results suggest that one function of
      CLIC-2 might be to limit Ca2+ release from internal stores in cells.

PMID- 15147739
TI  - Applying proteomic methodologies to analyze the effect of hexamethylene
      bisacetamide (HMBA) on proliferation and differentiation of human gastric
      carcinoma BGC-823 cells.
AB  - Human gastric carcinoma BGC-823 cells underwent morphological differentiation and
      cell cycle arrest in vitro when treated with 5mM hexamethylene bisacetamide
      (HMBA) for 48h. To further understand the mechanism of HMBA-induced
      differentiation, proteomic methodologies were applied to screen and identify
      altered proteins involved in the commitment of BGC-823 cells to differentiate.
      Five distinct altered proteins were acquired by two-dimensional (2-D) PAGE and
      were consequently identified as ras-related protein rab-35 (Rab-35), splice
      truncated isoform of transmembrane protease, serine 3 (serine TADG-12), regulator
      of G-protein signaling 1 (RGS1), ret finger protein-like 1 (RFPL1) and F-actin
      capping protein alpha-3 subunit (GSG3) by analysis of mass spectrograph. Of the
      five proteins, serine TADG-12 down-regulated under the detectable level after
      HMBA treatment, Rab-35, RGS1 and RFPL1 sharply up-regulated within the HMBA
      induced BGC-823 cells, and GSG3, appearing in both treated and untreated cells,
      remarkably increased within BGC-823 cells after HMBA stimulation. Our results
      implicate that the molecular mechanism of BGC-823 cell differentiation in
      response to HMBA may involved in complex processes including a signaling network
      linking vesicle transport, actin cytoskeleton remodeling except for morphology
      differentiation, cell cycle G1 arrest.

PMID- 15147740
TI  - Cellular stress-related protein expression in Helicobacter pylori-infected
      gastric epithelial AGS cells.
AB  - Helicobacter pylori infection leads to gastroduodenal inflammation, peptic
      ulceration, and gastric carcinoma. Moreover, H. pylori may induce disease
      specific protein expression in gastric epithelial cells. The present study was
      aimed at determining differentially expressed proteins in H. pylori-infected
      gastric epithelial AGS cells. AGS cells were treated with H. pylori at a
      bacterium/cell ratio of 300:1 for 12 h. Altered protein patterns as separated by
      two-dimensional electrophoresis using pH gradients of 4-7 were conclusively
      identified by matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF MS) analysis of the peptide digests. Four differentially
      expressed proteins, whose expression levels were increased by more than two-fold
      in H. pylori-infected cells, were analyzed. These proteins (14-3-3 protein
      alpha/beta, cullin homolog 3, alpha-enolase, ezrin) are known to be related to
      cell proliferation, cell adhesion, and carcinogenesis, and may be mediated by
      cellular stress, such as reactive oxygen species. In conclusion, the
      identification of these differentially expressed proteins provide valuable
      information for the understanding of the pathophysiologic mechanisms of H. pylori
      induced gastric diseases, and may be useful as prognostic indices of H. pylori
      related gastric disorders.

PMID- 15147741
TI  - Purification and characterization of decorin from the culture media of MRC-5
      cells.
AB  - Myofibroblasts play an important role in fibrogenesis. Myofibroblasts secrete
      several components of the extracellular matrix, including decorin. To clarify the
      properties of decorin synthesized by myofibroblasts, we have purified and
      characterized decorin secreted into culture medium by the myofibroblast cell line
      MRC-5. Decorin was purified by successive chromatography steps using Hitrap Q and
      Superdex 200. Purified decorin showed a broad band on SDS-polyacrylamide gel
      electrophoresis, which was resolved into two smaller molecular weight bands after
      digestion with chondroitinase ABC. Further digestion with N-glycanase resolved
      these two bands into a single band, indicating that the N-glycation pattern of
      decorin is heterogeneous. The N-terminal amino acid sequence analysis of the
      purified protein and its reactivity towards an antibody raised against a C
      terminal peptide of decorin indicate that MRC-5 cells secrete full-length decorin
      into the culture medium. To characterize the glycosaminoglycan chains attached to
      decorin, glycosaminoglycans from the purified protein were treated with
      chondroitinase ACI, chondroitinase ACII, chondroitinase ABC and chondroitinase B.
      The resulting disaccharides were analyzed by chromatography, which indicated that
      decorin secreted by MRC-5 cells is a dermatan sulfate proteoglycan. In
      conclusion, the decorin secreted by MRC-5 cells has similar characteristics to
      the decorin expressed in several tissues. Thus, culturing MRC-5 cells may be
      highly useful for studying the role of decorin and myofibroblasts in fibrosis.

PMID- 15147742
TI  - Influence of 2-chlorodeoxyadenosine (cladribine) on human erythrocytes.
AB  - 2-Chlorodeoxyadenosine (2-CdA, cladribine) is one of the newest chemotherapy
      drugs which has been around and in use for a few years. Drug in tumour cells
      causes the inhibition of DNA synthesis and repair processes in replication cells,
      and the accumulation of DNA strand breaks in nonproliferating cells. The present
      study was undertaken to characterize the influence of cladribine on the fluidity
      of the lipid bilayer and protein conformation in human erythrocytes. The effect
      of cladribine on the erythrocyte membrane structure was examined by electron spin
      resonance (ESR) spectroscopy and fluorescence measurements. It was observed that
      under the studied conditions (c: 0.1-5 microg/ml, t = 1 h, 37 degrees C),
      cladribine localised mainly in the erythrocyte membrane and affected its
      organization. The alterations in the fluidity were observed mainly in the deeper
      regions of the cell membrane. The incorporation of drug into human erythrocytes
      also caused negligible conformational alterations of membrane cytoskeletal
      proteins and did not change the internal viscosity of the cells. We can conclude
      from these data that 2-CdA in vitro is significantly much less toxic to
      erythrocytes than anthracycline drugs, which are used in treatment of leukemias.
      However, the higher concentrations of 2-CdA (about 5 microg/ml) can be also toxic
      to erythrocytes.

PMID- 15147743
TI  - Tissue inhibitor of metalloproteinases-2 growth-stimulatory activity is mediated
      by nuclear factor-kappa B in A549 lung epithelial cells.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are pleiotropic factors that
      function as key regulators of extracellular matrix remodeling. They exhibit
      multifunctional roles including cell growth-stimulating activities and protection
      from apoptosis. In the present study, we showed that human recombinant TIMP-2
      (hrTIMP-2) promotes growth of A549 lung cells. This effect was accompanied by
      increase in nuclear factor-kappa B (NF-kappaB) activity 24h after exposure as
      determined by electrophoretic mobility shift assay (EMSA) analysis. This effect
      was correlated with downregulation of IkappaBalpha and beta proteins and later
      increases in Bcl-3, IkappaB, and cyclin D1 proteins. Blocking induction of NF
      kappaB activity using a dominant-negative mutated version of IkappaBalpha
      abrogated NF-kappaB activation and cell proliferation.

PMID- 15147744
TI  - Optical characterization of mammalian tissues by laser reflectometry and Monte
      Carlo simulation.
AB  - The optical characterization of various goat organs/tissues, by measurement of
      the spatial variation of the diffuse reflectance from the surface by laser multi
      probe reflectometer, is carried out. For determination of the optical parameters,
      these profiles are matched by iterative procedures with that obtained by Monte
      Carlo simulation by best-fit procedure with chi value 0.99. The first set of
      measurements is carried out with milk phantom. Thereafter, the absorption and
      scattering coefficients and anisotropy parameter of goat's heart, lungs, kidney,
      liver, spleen, skeletal muscle, brain and adipose tissues are measured. These
      parameters vary over a wide range, which is in agreement with results reported by
      others. Based on these data, their laser scattering profiles along the depth in
      terms of depth of penetration (DP) and maximum scattered beam width (MSBW) are
      determined. These are maximum (0.030 and 0.038 m) for kidney and minimum (0.007
      and 0.006 m) for spleen, respectively. The backscattered intensity measured
      0.002, 0.004 and 0.006 m away from the beam entry point shows the maximum
      contribution from the respective depths, irrespective of the nature of the
      organs/tissues.

PMID- 15147745
TI  - In-plane electronic speckle pattern of interference (ESPI) with optical fibre
      system applied to the study of the human jaw.
AB  - The standard illumination set-up for measurement of in-plane displacement in
      electronic speckle pattern of interference (ESPI) requires the use of two oblique
      coherent beams for the illumination of the object. These two beams define a
      direction in the plane perpendicular to the optical axis in which the
      displacement can be measured, while in the perpendicular direction the
      interferometer has no sensitivity. In this paper, a new ESPI system for the
      measurement of in-plane displacements is used. The novelty presented by this
      assembly is the use of optical fibres to split and guide the light beams. In this
      way, it is possible to vary with great precision and ease the direction of the
      projected beams and, consequently, the direction of the plane in which the
      displacements undergone by the object can be studied. This set-up makes possible
      the study of objects with complex geometries, which have deformations with
      unknown symmetry. We present results obtained with this interferometer applied to
      the study of the mechanical behaviour of the human jaw.

PMID- 15147746
TI  - Gaussian mixture models of ECoG signal features for improved detection of
      epileptic seizures.
AB  - PURPOSE: To investigate the potential for improving the performance of the Osorio
      Frei seizure detection algorithm (OFA) by incorporating multiple FIR filters
      operating in parallel and Gaussian mixture models (GMM) for ECoG features
      distributions, thus creating "hybrid" system. METHODS: The "hybrid" algorithm
      decomposes the signal into four subbands, using wavelets, after which relevant
      features are extracted for each subband. Following these steps, multivariate GMM
      are developed for seizure and non-seizure states, using training segments. State
      classification is based on thresholding of the likelihood ratio of seizure vs.
      non-seizure data. Multiple comparisons are performed between this "hybrid" and a
      modified version of the OFA suitable for this purpose, using as indices false
      positives (FP), false negatives (FN) and speed of detection. RESULTS: GMM
      improved speed of detection over the modified OFA at negligible FP levels. The
      average detection delay from expert visually placed electrographic onset over all
      seizures was reduced from 4.8 s for modified OFA to 1.8 s for GMM (p < 0.002)
      Individualized training by subject proved superior to group-based training.
      CONCLUSIONS: This work introduces multi-feature extraction from ECoG signals
      together with use of Gaussian mixtures to model them, as tools to improve
      automated seizure detection. At the clinical level, this approach appears to
      increase warning time and with it the window during which safety measures and
      seizure blockage may be implemented, at an affordable computational cost and with
      negligible FP rate.

PMID- 15147747
TI  - Does the conduction velocity distribution change along the nerve?
AB  - Nerve conduction velocity distribution (CVD) is a very useful tool to examine the
      state and function of nerves. Only one record of compound action potential (CAP)
      may be sufficient to determine the CVD if the shape functions of the single fiber
      action potentials (SFAP) of fibers are known. Otherwise, CAP recordings from
      different locations are necessary to determine CVD. In this case, we confront the
      problem of whether the shape of the CVD changes along the nerve, because many
      methods that attempt to determine the CVD are based on the assumption that the
      CVD is invariant along the nerve. There is not a complete solution to this
      problem, but there are many suggestions allied with the recording conditions to
      minimise this effect. The other effect that may influence both shapes of CAP and
      CVD along the nerve is the volume conductor effect. If a suitable model could
      isolate and eliminate the volume conductor effect, then the spatial variation of
      CVD may be attributed to the natural conditions of the nerve. In this study, we
      followed a procedure to eliminate volume conductor effect and then applied our
      previously published model to examine the spatial variations in CVD. The results
      show that CVDs estimated at discrete points along the nerve trunk have
      significantly different patterns. Consequently, it may be concluded that CVD is
      not uniform along an isolated nerve trunk contrary to the assumptions of the most
      CVD estimation methods.

PMID- 15147748
TI  - LES modelling of flow in a simple airway model.
AB  - Detailed information about the flow field pattern is highly important in
      accurately predicting particle deposition sites in the human airway. Flow in the
      upper airway during heavy breathing can have a Reynolds number as high as 9300,
      and therefore presents turbulent features. Although turbulence is believed to
      have an important effect on the airflow and other transport processes in the
      bronchial tree, to date both theoretical and numerical studies have predominantly
      assumed the flow to be laminar. In this paper, transitional/turbulent flow during
      inspiration is studied using a large eddy simulation (LES) in a single asymmetric
      bifurcation model of human upper airway. The influence of the non-laminar flow on
      the patterns and the particle paths is investigated in both 2D and 3D models.
      Throughout the investigation, comparisons with the laminar and conventional k-
      models for the same configuration and flow conditions are made. The LES model is
      also carefully validated against published experimental data in a stenotic tube
      model. The results demonstrate that the LES model is capable of capturing
      instantaneous eddy formation and flow separation in (almost) laminar,
      transitional and turbulent flow regimes, and hence may be used as a powerful and
      practical tool to provide much of the detailed flow information required for
      tracing the particle trajectories and particle deposition in human airways.

PMID- 15147749
TI  - Validation of the relative 3D orientation of vertebrae reconstructed by bi-planar
      radiography.
AB  - The three dimensional (3D) reconstruction of the spine can be obtained by
      stereoradiographic techniques. To be safely used on a routine clinics basis,
      stereoradiography must provide both accurate vertebral shape and coherent
      position. Although the accuracy of the reconstructed morphology of the vertebrae
      is well documented, only few authors studied the accuracy of the vertebral
      orientation. Therefore, this paper focuses on the evaluation of the orientation
      accuracy of the reconstructed vertebrae (obtained by non-stereo corresponding
      point technique) considering either a 178 point vertebral model or a 6 point
      vertebral model (previously proposed in the literature). Five dried vertebrae
      were fixed on holders containing four markers each. The 3D reconstruction of both
      vertebrae and markers were obtained by stereoradiographic techniques. Using least
      square method matching from one position to another, the relative orientation was
      computed for the vertebral models (6 or 178 points) and the four markers. These
      vertebral and holder orientations were compared (considering the holder's one as
      reference). The repeatability of these relative orientations (vertebrae and
      holders) was also evaluated. The mean (RMS) orientation error of 178 point
      vertebral model was 0.6 degrees (0.8 degrees ), for lateral rotation, 0.7 degrees
      (1.0 degrees ) for sagittal rotation and 1.4 degrees (1.9 degrees ) for axial
      rotation. The intra-observer repeatability was 0.5 degrees (0.7 degrees ) for
      lateral rotation, 0.7 degrees (0.8 degrees ) for sagittal rotation and 0.9
      degrees (1.2 degrees ) for axial rotation. The orientation was found more
      accurate and precise when using the 178 point vertebral model than when using the
      basic 6 point vertebral model. The relative orientation (in post-operative follow
      up with respect to the pre-operative examination) of the vertebrae of one
      scoliotic patient was performed as an example of clinical application. The
      stereoradiographic method is a reliable 3D quantitative tool to assess the spine
      deformity, that can be used in clinics for the follow-up of scoliotic patients.

PMID- 15147750
TI  - Multispectral classification techniques for terahertz pulsed imaging: an example
      in histopathology.
AB  - Terahertz pulsed imaging is a spectroscopic imaging modality using pulses of
      electromagnetic radiation (100 GHz-10 THz), and there has been recent interest in
      studying biomedical specimens. It is usual to display parametric images derived
      from the measured pulses. In this work, classification was achieved by applying
      multispectral clustering techniques to sets of parametric images. It was
      hypothesised that adequate information for clustering was carried in a small
      number of parametric images, providing these were weighted by complementary
      physical properties. Materials prepared for histopathological examination were
      chosen because their condition remained stable during long imaging periods and
      because their dehydrated state led to greater penetration of the radiation. Two
      specimens were examined in this pilot study, one of basal cell carcinoma and one
      of melanoma. Unsupervised ISODATA classification using three selected parametric
      terahertz pulsed images was compared qualitatively with k-means classification
      using the shape of the whole time series, and with conventional stained
      microscope slides. There was good qualitative agreement between the
      classifications. Classifications were consistent with the morphological
      appearances expected, but further work is required to determine if tumour
      discrimination is possible. The results have implications for the future
      development of the technique as the need for only a small number of features
      could lead to considerably reduced acquisition times.

PMID- 15147751
TI  - Basic characteristics of the radio imaging method for biomedical applications.
AB  - The radio imaging method (RIM), a technology used practically for geophysical
      surveys, was applied to biomedical measurements. The characteristics of a subject
      between a pair of simple loop antennas were measured by using a feeble
      electromagnetic wave of low frequency. Water distribution inside the human body
      was expected to be measured, as well as the original method imaged mineral
      distributions. In geophysical surveys, finer resolution is provided than a
      wavelength of the electromagnetic wave. This was also expected for biomedical
      measurements. An acrylic water tank was used as a phantom of the abdominal
      portion of the human body, and basic measurements were performed with the
      phantom. The inner tank of the phantom, whose cross section was 6 x 8 cm, was
      detected by the method when the frequency was 54 MHz or the wavelength was nearly
      6 m in free space. The resolution provided by the experiment suggested that the
      proposed method was effective even if the wavelength was longer than the
      dimensions of the targeted area. The advantage of the method is simplicity,
      economy and safety. The authors are looking for specific applications for
      example, a urination sensor or a vital monitor for in-home care, where the strong
      points of the method are suitable.

PMID- 15147752
TI  - Zinc-metalloproteases in insects: ACE and ECE.
AB  - Research on the angiotensin-converting enzyme (ACE) in insects has substantially
      advanced during the recent decade. The cloning of this enzyme in many insect
      species, the determination of the 3D-structure and several molecular and
      physiological studies have contributed to the characterization of insect ACE as
      we know it today: a functional enzyme with a putative role in reproduction,
      development and defense. The discovery of the endothelin-converting enzyme in
      insects occurred more recently and cloning of the corresponding cDNA has been
      carried out in only one insect species so far. However, activity studies and
      analysis of insect genomes indicate that this enzyme is also widely distributed
      among insect species. Making hypotheses about its putative function would be
      preliminary, but its wide tissue distribution suggests a major and diverse
      biological role.

PMID- 15147754
TI  - Mining single nucleotide polymorphisms from EST data of silkworm, Bombyx mori,
      inbred strain Dazao.
AB  - We made use of 81,635 expressed sequence tags (ESTs) derived from 12 different
      cDNA libraries of the silkworm, Bombyx mori, inbred strain Dazao (P50), to
      identify high-quality candidate single nucleotide polymorphisms (SNPs). By PHRAP
      assembling, 12,980 contigs containing 11,537 contigs assembled by more than one
      read were obtained, and 101 candidate SNPs and 27 single base
      insertions/deletions were identified from 117 contigs assembled from 1576 high
      quality reads base-called with PHRED and screened on the basis of the
      neighborhood quality standard (NQS). Simultaneously, we also predicted 40 SNPs in
      coding regions (cSNPs), of which 26 were predicted to lead to amino acid non
      synonymous variations and 14 synonymous substitutions. Also, the 1.66:1 ratio of
      transition/transversion is different from that of other insects. As the first SNP
      analysis of a Lepidoptera, B. mori, the single nucleotide polymorphic density is
      estimated to be 1.3 x 10(-3) by sequence diversity. This analysis shows that
      expressed sequences from multiple libraries may provide an abundant source of
      comparative reads to mine for cSNPs from the silkworm genome.

PMID- 15147753
TI  - Cloning, expression and functional analysis of an octopamine receptor from
      Periplaneta americana.
AB  - Octopamine regulates multiple physiological functions in invertebrates. The
      biological effects of octopamine and the pharmacology of octopamine receptors
      have been extensively studied in the American cockroach, Periplaneta americana.
      This paper reports the cloning of the first octopamine receptor from Periplaneta
      americana. A cDNA encoding a putative 7 transmembrane receptor was isolated from
      the head of Periplaneta americana. The encoded protein contains 628 amino acids
      and has sequence similarity to other biogenic amine receptors. This protein was
      expressed in COS-7 cells for radioligand binding studies using the antagonist 3H
      yohimbine. Competitive binding comparing biogenic amines that could potentially
      function as endogenous ligands demonstrated this receptor had the highest
      affinity for octopamine (Ki = 13.3 microM) followed by tyramine, dopamine,
      serotonin and histamine. Octopamine increased both cAMP levels (EC50 = 1.62
      microM) and intracellular concentrations of calcium through the receptor
      expressed in HEK-293 cells. Tyramine increased levels of both of these second
      messengers but only at significantly higher concentrations than octopamine. The
      cAMP increase by octopamine was independent of the increase in calcium.
      Competitive binding with antagonists revealed this receptor is similar to Lym oa1
      from Lymnaea stagnalis. The data indicate that this cDNA is the first octopamine
      receptor cloned from Periplaneta americana and therefore has been named Pa oa1.

PMID- 15147755
TI  - Immunocharacterization of the DNA puff BhC4-1 protein of Bradysia hygida
      (Diptera: Sciaridae).
AB  - The DNA puff BhC4-1 gene is amplified and highly expressed in the salivary gland
      of Bradysia hygida late larvae. Using affinity-purified polyclonal antibodies we
      have identified the product of the BhC4-1 gene as a 43 kDa polypeptide which is
      present in extracts of salivary glands from late fourth instar larvae and in the
      corresponding gland secretion, but not in glands from earlier stages. We also
      demonstrate that this protein is produced mainly in the S1 and S3 regions of the
      salivary gland, where BhC4-1 amplification levels are more pronounced and larger
      amounts of mRNA are produced. By immunoelectron microscopy the BhC4-1 protein was
      detected in secretory granules of the S1 and S3 regions, and localized in fibrous
      structures present in the saliva.

PMID- 15147757
TI  - Towards a comprehensive view of the primary structure of venom proteins from the
      parasitoid wasp Pimpla hypochondriaca.
AB  - Venom from the parasitoid wasp Pimpla hypochondriaca has potent in vivo activity
      against insect haemocytes and disrupts host immune responses. Using hybridisation
      techniques, and more recently random sequence analysis, we had previously
      identified cDNAs encoding 10 venom proteins from this wasp and deduced their
      primary structures. We have now extended the random sequence analysis and
      discovered a further nine cDNAs encoding proteins with predicted signal
      sequences. The mature proteins were calculated to have masses of between 4 and 22
      kDa. Post-signal sequence residues predicted from the cDNAs matched those derived
      by Edman degradation from venom proteins separated using gel filtration and
      reverse phase chromatography, confirming that the cloned cDNAs encode proteins
      which are secreted into the venom sac. Proteins containing at least six cysteine
      residues were abundant and seven of these cysteine-rich venom proteins, cvp1-7,
      were identified. The sequences of some of these proteins were similar, or
      contained similar cysteine arrangements, to Kunitz type protease inhibitors,
      pacifastin, the trypsin inhibitor domain protein family, atracotoxin and omega
      conotoxin, respectively, which occur in a diverse range of animals including
      spiders, molluscs, humans and grasshoppers. Two small venom proteins, svp1 and
      svp2, as well as cvp7 did not have similar sequences to proteins in the GenBank
      protein database suggesting they may be highly specialised venom components. The
      random sequencing approach has provided a rapid means of determining the primary
      structure of the majority of Pimpla hypochondriaca venom proteins.

PMID- 15147756
TI  - An insight into the salivary transcriptome and proteome of the adult female
      mosquito Culex pipiens quinquefasciatus.
AB  - To obtain an insight into the salivary transcriptome and proteome (sialome) of
      the adult female mosquito Culex quinquefasciatus, a cDNA library was randomly
      sequenced, and aminoterminal information for selected proteins and peptides was
      obtained. cDNA sequence clusters coding for secreted proteins were further
      analyzed. The transcriptome revealed messages coding for several proteins of
      known families previously reported in the salivary glands of other blood-feeding
      insects as well as immune-related products such as C-type lectin, gambicin, and
      members of the prophenol oxidase cascade. Additionally, several transcripts
      coding for low-complexity proteins were found, some clearly coding for mucins.
      Many novel transcripts were found, including a novel endonuclease previously
      described in crabs and shrimps but not in insects; a hyaluronidase, not described
      before in mosquito salivary glands but found in venom glands and in salivary
      glands of sand flies and black flies; several cysteine-rich peptides with
      possible anticlotting function, including one similar to a previously described
      nematode family of anti-proteases; and a completely novel family of cysteine- and
      tryptophane-rich proteins (CWRC family) for which 12 full-length sequences are
      described. Also described are 14 additional novel proteins and peptides whose
      function and/or family affiliation are unknown. In total, 54 transcripts coding
      for full-length proteins are described. That several of these are translated into
      proteins was confirmed by finding the corresponding aminoterminal sequences in
      the SDS-PAGE/Edman degradation experiments. Electronic versions of all tables and
      sequences can be found at
      http://www.ncbi.nlm.nih.gov/projects/Mosquito/C_quinquefasciatus_sialome.

PMID- 15147758
TI  - The mechanism of alphaIIbbeta3 antagonism by savignygrin and its implications for
      the evolution of anti-hemostatic strategies in soft ticks.
AB  - Savignygrin, a alphaIIbbeta3 antagonist presents the RGD sequence on the
      substrate-binding loop of the (BPTI-fold). This study investigated whether this
      is the only integrin-targeting motif associated with its mechanism. It forms a
      tight-binding complex with alphaIIbbeta3 that is resistant to SDS dissociation
      under reducing and non-reducing conditions, but not to temperature or EDTA. The
      same complex is formed on resting and activated platelets, as well as aggregated
      platelets that have been disaggregated with savignygrin. Binding of FITC labeled
      savignygrin to platelets show that the binding kinetics and affinity of
      savignygrin is similar for resting and activated platelets (Kd approximately 50
      70 nM). Binding to resting or activated platelets was significantly inhibited by
      two savignygrin peptide fragments, S2 (GSRGDEDATFG) and S3 (FDREDGGSRQG) that
      correspond with two specific loop-like areas in the structure of savignygrin that
      together form a continuous binding interface. The inability of S3 to inhibit
      platelet aggregation indicates that it targets a novel ligand-binding site. A
      model of alphaIIbbeta3 based on the recent crystal structure of alphavbeta3 into
      which the RGD sequence of savignygrin was docked shows that savignygrin lies
      along the interface formed by the two subunits. A novel mode of integrin
      antagonism is indicated that includes the targeting of distinct sites on the
      alphaIIbbeta3 subunits. The S2 and S3 loops are not involved in the mechanisms of
      the related soft tick blood coagulation inhibitors and suggest that this allowed
      their evolution as integrin targeting motifs.

PMID- 15147759
TI  - Exon-intron structure of outlier tick lipocalins indicate a monophyletic origin
      within the larger lipocalin family.
AB  - All tick proteins assigned to the lipocalin family lack the structural conserved
      regions (SCRs) that are characteristic of the kernel lipocalins and can thus be
      classified as outliers. These tick proteins have been assigned to the tick
      lipocalin family based on database searches that indicated homology between tick
      sequences and the fact that the histamine binding protein (HBP2) from the hard
      tick Rhipicephalus appendiculatus (Ixodidae) shows structural similarity to the
      lipocalin fold. Sequence identity between kernel and outlier lipocalins falls
      below 20% and the question raised is whether the outlier and kernel lipocalins
      are truly homologous. More specifically in the case of the tick lipocalins,
      whether their structural fold is derived from the lipocalin fold or whether
      convergent evolution resulted in the generation of the basic lipocalin-like fold
      which consists of an eight stranded continuous anti-parallel beta-barrel
      terminated by a C-terminal alpha-helix that lies parallel to the barrel. The
      current study determined the gene structure for HBP2 and TSGP1, TSGP2 and TSGP4,
      lipocalins identified from the soft tick Ornithodoros savignyi (Argasidae). All
      tick lipocalins have four introns (A-D) with conserved positions and phases
      within the tick lipocalin sequence alignment. The positions and phase information
      are also conserved with regard to the rest of the lipocalin family. Phylogenetic
      analysis using this information shows conclusively that tick lipocalins are
      evolutionary related to the rest of the lipocalin family. Tick lipocalins are
      grouped within a monophyletic clade that indicates a monophyletic origin within
      the tick lineage and also group with the other arthropod lipocalins in a larger
      clade. Phylogenetic analysis of sequence alignments based on conserved secondary
      structure of the lipocalin fold support the conclusions from the gene structure
      trees. These results indicate that exon-intron arrangement can be useful for the
      inclusion of outlier lipocalins within the larger lipocalin family.

PMID- 15147760
TI  - Deletion of the Na/K-ATPase alpha1-subunit gene (Atp1a1) does not prevent
      cavitation of the preimplantation mouse embryo.
AB  - Increases in Na/K-ATPase activity occur concurrently with the onset of cavitation
      and are associated with increases in Na(+)-pump subunit mRNA and protein
      expression. We have hypothesized that the alpha1-isozyme of the Na/K-ATPase is
      required to mediate blastocyst formation. We have tested this hypothesis by
      characterizing preimplantation development in mice with a targeted disruption of
      the Na/K-ATPase alpha1-subunit (Atp1a1) using embryos acquired from matings
      between Atp1a1 heterozygous mice. Mouse embryos homozygous for a null mutation in
      the Na/K-ATPase alpha1-subunit gene are able to undergo compaction and
      cavitation. These findings demonstrate that trophectoderm transport mechanisms
      are maintained in the absence of the predominant isozyme of the Na(+)-pump that
      has previously been localized to the basolateral membranes of mammalian
      trophectoderm cells. The presence of multiple isoforms of Na/K-ATPase alpha- and
      beta-subunits at the time of cavitation suggests that there may be a degree of
      genetic redundancy amongst isoforms of the catalytic alpha-subunit that allows
      blastocyst formation to progress in the absence of the alpha1-subunit.

PMID- 15147761
TI  - Slit-Robo signalling prevents sensory cells from crossing the midline in
      Drosophila.
AB  - Maintenance of bilateral symmetry throughout animal development requires that
      both left and right halves of the body follow nearly identical patterns of cell
      proliferation, differentiation, death and migration. During formation of the
      perfectly bilateral Drosophila larval peripheral nervous system (PNS), the
      sensory precursor cells of the ventral multidendritic neuron vmd1a originating
      from each hemisegment migrate away from the ventral midline. Our observations
      indicate that in slit mutant embryos, as well as in robo, robo2 double mutants,
      sensory precursor cells of the left and right vmd1a neurons aberrantly cluster at
      the midline and then the pair of vmd1a neurons migrate to their final position on
      the same side of the embryo. This results in disruption of PNS bilateral
      symmetry. Expression of slit at the midline rescues the slit mutant vmd1a
      phenotype, suggesting that midline-secreted Slit activates Robo/Robo2 signalling
      to control the migration of the vmd1a sensory precursor cells. Our study
      indicates that midline-secreted Slit prevents vmd1a sensory cells from crossing
      the midline and thereby maintains PNS bilateral symmetry during development.

PMID- 15147762
TI  - Combinatorial Wnt control of zebrafish midbrain-hindbrain boundary formation.
AB  - Wnt signaling is known to be required for the normal development of the
      vertebrate midbrain and hindbrain, but genetic loss of function analyses in the
      mouse and zebrafish yield differing results regarding the relative importance of
      specific Wnt loci. In the zebrafish, Wnt1 and Wnt10b functionally overlap in
      their control of gene expression in the ventral midbrain-hindbrain boundary
      (MHB), but they are not required for the formation of the MHB constriction.
      Whether other wnt loci are involved in zebrafish MHB development is unclear,
      although the expression of at least two wnts, wnt3a and wnt8b, is maintained in
      wnt1/wnt10b mutants. In order to address the role of wnt3a in zebrafish, we have
      isolated a full length cDNA and examined its expression and function via
      knockdown by morpholino antisense oligonucleotide (MO)-mediated knockdown. The
      expression pattern of wnt3a appears to be evolutionarily conserved between
      zebrafish and mouse, and MO knockdown shows that Wnt3a, while not uniquely
      required for MHB development, is required in the absence of Wnt1 and Wnt10b for
      the formation of the MHB constriction. In zebrafish embryos lacking Wnt3a, Wnt1
      and Wnt10b, the expression of engrailed orthologs, pax2a and fgf8 is not
      maintained after mid-somitogenesis. In contrast to acerebellar and no isthmus
      mutants, in which midbrain and hindbrain cells acquire new fates but cell number
      is not significantly affected until late in embryogenesis, zebrafish embryos
      lacking Wnt3a, Wnt1 and Wnt10b undergo extensive apoptosis in the midbrain and
      cerebellum anlagen beginning in mid-somitogenesis, which results in the absence
      of a significant portion of the midbrain and cerebellum. Thus, the requirement
      for Wnt signaling in forming the MHB constriction is evolutionarily conserved in
      vertebrates and it is possible in zebrafish to dissect the relative impact of
      multiple Wnt loci in midbrain and hindbrain development.

PMID- 15147763
TI  - The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of
      mammalian Ring1 proteins.
AB  - In Drosophila, the Polycomb group (PcG) of genes is required for the maintenance
      of homeotic gene repression during development. Here, we have characterized the
      Drosophila ortholog of the products of the mammalian Ring1/Ring1A and Rnf2/Ring1B
      genes. We show that Drosophila Ring corresponds to the Sex combs extra (Sce), a
      previously described PcG gene. We find that Ring/Sce is expressed and required
      throughout development and that the extreme Pc embryonic phenotype due to the
      lack of maternal and zygotic Sce can be rescued by ectopic expression of
      Ring/Sce. This phenotypic rescue is also obtained by ectopic expression of the
      murine Ring1/Ring1A, suggesting a functional conservation of the proteins during
      evolution. In addition, we find that Ring/Sce binds to about 100 sites on
      polytene chromosomes, 70% of which overlap those of other PcG products such as
      Polycomb, Posterior sex combs and Polyhomeotic, and 30% of which are unique. We
      also show that Ring/Sce interacts directly with PcG proteins, as it occurs in
      mammals.

PMID- 15147764
TI  - Roles of Hroth, the ascidian otx gene, in the differentiation of the brain
      (sensory vesicle) and anterior trunk epidermis in the larval development of
      Halocynthia roretzi.
AB  - Otx genes are expressed in the anterior neural tube and endoderm in all of the
      chordates so far examined. In mouse embryos, important roles of otx genes in the
      brain development have been well documented. However, roles of otx genes in other
      chordate species have been less characterized. To advance our understanding about
      roles of otx genes in chordates, we have studied Hroth, otx of the ascidian,
      Halocynthia roretzi. Hroth is expressed in the anterior part of the neural tube
      (the sensory vesicle), the endoderm and anterior epidermis in the development. In
      this study, we investigated roles of Hroth in the larval development through an
      antisense morpholino oligonucleotides (MOs) approach. Embryos injected with Hroth
      targeting MO (Hroth knockdown embryos) developed into larvae without the adhesive
      organ, sensory pigment cells and cavity of the sensory vesicle. The tissues, in
      which defects were observed, are derived from anterior-animal cells of the embryo
      in early cleavage stages. During cleavage stages, Hroth is also expressed in the
      endoderm precursors of the vegetal hemisphere. However, Hroth expression in the
      anterior endoderm precursors do not seem to be essential for the above defects,
      since MO injection into the anterior-animal but not anterior-vegetal pair cells
      at the 8-cell stage gave the defects. Analysis of marker gene expression
      demonstrated that the fate choice of the sensory vesicle precursors and the
      specification of the sensory vesicle territory occurred normally, but the
      subsequent differentiation of the sensory vesicle was severely affected in Hroth
      knockdown embryos. The anterior trunk epidermis including the adhesive organ
      forming region was also affected, indicating that anterior epidermal patterning
      requires Hroth function. Based on these findings, similarities and differences in
      the roles of otx genes between ascidians and mice are discussed.

PMID- 15147765
TI  - Emx1 and Emx2 cooperate in initial phase of archipallium development.
AB  - Emx1 and Emx2 are mouse cognates of the Drosophila head gap gene, ems. Previously
      we have reported that the dentate gyrus is affected in Emx2 single mutants, and
      defects are subtle in Emx1 single mutants. In most of the cortical region Emx1
      and Emx2 functions would be redundant. To test this assumption here we examined
      the Emx1 and Emx2 double mutant phenotype. In the double mutants the archipallium
      was transformed into the roof without establishing the signaling center at the
      cortical hem and without developing the choroid plexus. We propose that Emx1 and
      Emx2 cooperate in generation of the boundary between the roof and archipallium;
      these genes develop the archipallium against the roof. This process probably
      occurs immediately after the neural tube closure concomitant with the Emx1
      expression.

PMID- 15147766
TI  - Osa modulates the expression of Apterous target genes in the Drosophila wing.
AB  - The establishment of the dorsal-ventral axis of the Drosophila wing depends on
      the activity of the LIM-homeodomain protein Apterous. Apterous activity depends
      on the formation of a higher order complex with its cofactor Chip to induce the
      expression of its target genes. Apterous activity levels are modulated during
      development by dLMO. Expression of dLMO in the Drosophila wing is regulated by
      two distinct Chip dependent mechanisms. Early in development, Chip bridges two
      molecules of Apterous to induce expression of dLMO in the dorsal compartment.
      Later in development, Chip, independently of Apterous, is required for expression
      of dLMO in the wing pouch. We have conducted a modular P-element based EP
      (enhancer/promoter) misexpression screen to look for genes involved in Apterous
      activity. We have found Osa, a member of the Brahma chromatin-remodeling complex,
      as a positive modulator of Apterous activity in the Drosophila wing. Osa mediates
      activation of some Apterous target genes and repression of others, including
      dLMO. Osa has been shown to bind Chip. We propose that Chip recruits Osa to the
      Apterous target genes, thus mediating activation or repression of their
      expression.

PMID- 15147768
TI  - No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in
      organotypic rat hippocampal cultures.
AB  - MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic
      serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with
      highest affinity for the first. Whether 5-HT2A receptor density decreases due to
      MDMA's direct effect on postsynaptic serotonin receptors is at present not known.
      This study analyzes whether direct stimulation of the postsynaptic 5-HT2A
      receptor by MDMA in organotypic hippocampal cultures results in cell death and
      downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old
      cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and
      5-HT2A to determine neurodegeneration, and changes in receptor density,
      respectively, resulted in no significant differences. MDMA's neurotoxicity and
      regulation of post-synaptic 5-HT2A receptors thus seems to require the presence
      of intact serotonergic terminals.

PMID- 15147767
TI  - EEG alpha power changes reflect response inhibition deficits after traumatic
      brain injury (TBI) in humans.
AB  - Brain damage due to traumatic brain injury (TBI) has been associated with
      deficits in executive functions and the dynamic control of behaviour. Event
      related brain potentials and spectral power data were recorded from eight TBI
      participants and eight matched controls while they completed a Go/NoGo response
      inhibition task. The TBI group was found to be significantly impaired at the task
      compared to controls, and exhibited abnormal N2 and P3 waveform components in
      response to NoGo stimuli relative to controls. Significant correlations were also
      found between alpha power, Go-trial RT and errors. We conclude that abnormal
      activity in the structures damaged in this group may render such patients less
      capable of maintaining a state of alpha desynchronisation compared to controls,
      resulting in poorer performance on the task.

PMID- 15147769
TI  - Human reactions to physical stimulus and the removal of such stimulus as recorded
      by magnetoencephalography.
AB  - We studied the cortical evoked fields elicited by the examiner's touch on
      glabrous skin of the subject's index finger. Two main components of evoked fields
      were elicited, and these dipoles were located in the primary somatosensory cortex
      contralateral to the side of the subject's index finger touched by the examiner.
      When the timing of removal of the examiner's finger triggered the data
      acquisition using the photosensor, the strength of the dipole from early evoked
      fields was stronger than that from late ones. We showed that these evoked fields
      were elicited by removal and touch of the examiner's finger respectively in
      response to the mechanical compression and decompression of the skin.

PMID- 15147770
TI  - Involvement of insulin-like growth factor binding protein-2 in activated
      microglia as assessed in post mortem human brain.
AB  - In vitro studies suggest that insulin-like growth factor (IGF)-I is a mitogen for
      microglia/macrophages. The actions of IGF-I are mediated by IGF-I receptors and
      modulated by IGF binding proteins (IGFBPs). The aim of this study was to
      investigate IGF-I receptors and IGFBPs in human microglia in normal brain white
      matter and active lesions of multiple sclerosis, which contain activated
      microglia/macrophages. Methods used were immunohistochemistry and confocal laser
      microscopy. IGF-I receptors were demonstrated in both resting and activated
      microglia. In resting conditions, microglia displayed no immunoreactivity for any
      of the six IGFBPs, whereas activated microglia/macrophages were immunoreactive
      for IGFBP-2 only. Our data suggest an important function for IGFBP-2 in IGF-I
      actions in activated microglia/macrophages in human brain.

PMID- 15147771
TI  - Effect of diets with different magnesium content in ischemic stroke rats.
AB  - Rats fed with low (0.015%), normal (0.08%) or high (0.32%) magnesium (Mg) diet
      for 5-6 weeks were subjected to photothrombosis-induced infarction. As compared
      to normal diet, Mg deprivation increased by 45% infarct volume at 24 h after
      photothrombosis but did not modify the lesion at 4 h after photothrombosis. Mg
      supplementation did not protect from infarction whatever the time point examined.
      No differences in pre-ischemic systolic blood pressure and glycemia as well as in
      post-ischemic kaliemia, calcemia and plasma antioxidant activity were observed
      between groups. However, plasma total Mg level correlated with plasma antioxidant
      activity at 4 h after photothrombosis. These results demonstrate that brains from
      Mg deficient rats are more susceptible to permanent focal ischemia than rats fed
      with normal or high Mg diet.

PMID- 15147772
TI  - Heterogeneous expression of CD59 on human Purkinje cells.
AB  - The expression of CD59 and other complement regulators was studied in human
      cerebellum from 14 individuals with no cerebellar pathology, from one patient
      with multiple sclerosis (MS) and from two patients with paraneoplastic cerebellar
      degeneration (PCD). CD59 was present on the Purkinje cells at various levels in
      eight of the 14 cases with no cerebellar pathology. CD59 was also present on the
      Purkinje cells of the patient with MS, but not on the scarce remaining Purkinje
      cells of the two patients with PCD. Other complement regulators (CD35, CD46 and
      CD55) were not expressed on the Purkinje cells, whereas CD59, CD46 and CD55 were
      present on the molecular, granulosa and endothelial cells. The results suggest
      that Purkinje cells not expressing CD59 could be especially prone to complement
      mediated damage.

PMID- 15147773
TI  - CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced
      microglial activation in mice.
AB  - CD45 is a membrane-bound protein tyrosine phosphatase expressed on all
      hemopoietic cells with multiple splice variants, including RA, RB, RC and RO. Our
      previous studies have shown that cross-linking of CD45 with an anti-CD45 antibody
      markedly inhibits LPS-induced microglia activation. In order to determine which
      of the CD45 isoforms may be responsible for these effects, we have investigated
      the expression of CD45 isoforms on cultured microglial cells using flow
      cytometric analysis. Data reveal that CD45RB is the predominant isoform expressed
      in murine primary cultured microglial cells. Furthermore, incubation of these
      cultured cells with anti-CD45RB antibody results in a reduction of microglial
      activation induced by LPS as evidenced by TNF-alpha production. As a validation
      of these findings in vivo, brain homogenates from anti-CD45RB antibody (MG23G2)
      injected animals that had been treated with LPS demonstrate a significant
      decrease in TNF-alpha levels compared to control mice treated with LPS plus
      vehicle. Taken together, these findings suggest that therapeutic agents that
      specifically stimulate the microglial CD45RB signaling pathway may be effective
      in suppressing microglial activation associated with several neurodegenerative
      disorders.

PMID- 15147774
TI  - Changes of motor cortical excitability in human subjects from wakefulness to
      early stages of sleep: a combined transcranial magnetic stimulation and
      electroencephalographic study.
AB  - The effect of sleep on human motor cortical excitability was investigated by
      evaluating the latency and amplitude of motor evoked potentials in ten subjects
      using transcranial magnetic stimulation. Motor evoked potentials and
      electroencephalographic data were recorded simultaneously and analyzed.
      Recordings were performed before, during and after a sleep period. A significant
      decrease in motor evoked potentials amplitude and a slight change in motor evoked
      potentials latency were noted in the recordings during the different sleep stages
      with a return to baseline values on awakening. A decrease in motor cortical
      excitability is suggested as explaining the effect of sleep.

PMID- 15147775
TI  - Clozapine prolongs hypotonic immobility in rats with bilateral 6-hydroxydopamine
      lesions of the striatum.
AB  - Clozapine does not induce classical catalepsy. One explanation is that endogenous
      dopamine (DA) readily displaces clozapine from postsynaptic striatal DA
      receptors. If the latter were true, then depletion of striatal DA should permit
      clozapine to induce classical catalepsy. Rats received bilateral sham or 6
      hydroxydopamine (6-OHDA) lesions of the striatum. Catalepsy using the bar test
      was assessed on days 21, 28 and 35 after i.p. vehicle, haloperidol (0.75 mg/kg)
      or clozapine (20 mg/kg). Brains were harvested on day 36 and striatal DA was
      assayed. A 97% depletion of striatal DA was associated with a significant
      increase in the duration of immobility after haloperidol or clozapine
      administration. Both in sham as well as in 6-OHDA lesioned animals, however, the
      duration of immobility was greater after haloperidol than after clozapine.
      Furthermore, clozapine-treated animals were hypotonic and did not show the
      classic rigidity of haloperidol catalepsy. While clozapine's low propensity to
      induce immobility in animals and extrapyramidal symptoms in man may depend in
      part on endogenous striatal DA, other mechanisms must also be involved.

PMID- 15147776
TI  - Effect of naloxone-precipitated morphine withdrawal on c-fos expression in rat
      corticotropin-releasing hormone neurons in the paraventricular hypothalamus and
      extended amygdala.
AB  - Morphine withdrawal is characterized by physical symptoms and a negative
      affective state. The 41 amino acid polypeptide corticotropin-releasing hormone
      (CRH) is hypothesized to mediate, in part, both the negative affective state and
      the physical withdrawal syndrome. Here, by means of dual-immunohistochemical
      methodology, we examined the co-expression of the c-Fos protein and CRH following
      naloxone-precipitated morphine withdrawal. Rats were treated with slow-release
      morphine 50 mg/kg (subcutaneous, s.c.) or vehicle every 48 h for 5 days, then
      withdrawn with naloxone 5 mg/kg (s.c.) or saline 48 h after the final morphine
      injection. Two hours after withdrawal rats were perfused transcardially and their
      brains were removed and processed for immunohistochemistry. We found that
      naloxone-precipitated withdrawal of morphine-dependent rats increased c-Fos
      immunoreactivity (IR) in CRH positive neurons in the paraventricular
      hypothalamus. Withdrawal of morphine-dependent rats also increased c-Fos-IR in
      the central amygdala and bed nucleus of the stria terminalis, however these were
      in CRH negative neurons.

PMID- 15147777
TI  - Activation of the human sensorimotor cortex during error-related processing: a
      magnetoencephalography study.
AB  - We studied error-related processing using magnetoencephalography (MEG). Previous
      event-related potential studies have documented error negativity or error-related
      negativity after incorrect responses, with a suggested source in the anterior
      cingulate cortex or supplementary motor area. We compared activation elicited by
      correct and incorrect trials using auditory and visual choice-reaction time
      tasks. Source areas showing different activation patterns in correct and error
      conditions were mainly located in sensorimotor areas, both ipsi- and
      contralateral to the response, suggesting that activation of sensorimotor
      circuits accompanies error processing. Additional activation at various other
      locations suggests a distributed network of brain regions active during error
      related processing. Activation specific to incorrect trials tended to occur later
      in MEG than EEG data, possibly indicating that EEG and MEG detect different
      neural networks involved in error-related processes.

PMID- 15147778
TI  - Phase shift detection in thalamocortical oscillations using
      magnetoencephalography in humans.
AB  - Magnetoencephalography was used to investigate exogenously stimulated oscillatory
      activity between cortex and thalamus resulting from clicks presented binaurally
      at the rate of 40 Hz. Analysis of the responses demonstrated activation of left
      and right auditory cortex, medial parietal cortex, thalamus, and cerebellum.
      Cross-correlations of the source waveforms revealed synchronicity between the
      auditory cortex sources (r > 0.9), auditory cortex and thalamic sources (r >
      0.7), and thalamic and parietal sources (r > 0.7). The 40 Hz response in auditory
      cortex occurred 6 ms after thalamic activation. Supporting earlier findings, the
      results demonstrate the networks involved in the maintenance of 40 Hz auditory
      steady-state response and will prove useful for the interrogation of dysfunction
      in disorders demonstrating thalamocortical dysrhythmia, such as schizophrenia,
      Parkinson's disease, and depression.

PMID- 15147779
TI  - Presence of translation elongation factor-1A in the rat cerebellar postsynaptic
      density.
AB  - This study examined a 55 kDa protein in the rat cerebellar postsynaptic density
      (PSD) fraction. The amino acid sequence of an HPLC-purified peptide derived from
      tryptic digestion of the protein was contained in eukaryotic translation
      elongation factor-1A (eEF1A, formerly known as eEF-1alpha). Immunoblot analysis
      showed that eEF1A is enriched in the PSD fraction and is tightly associated with
      the PSD 'core'. The association of eEF1A with the PSD was further evidenced by
      colocalization of the protein with PSD95, a PSD marker, in dissociated cerebellar
      cultures and immunoelectron microscopy of the adult rat cerebellum. Combined, our
      results indicate that eEF1A is associated with the PSD.

PMID- 15147780
TI  - Location of bladder and urethral sphincter motoneurons in the male guinea pig
      (Cavia porcellus).
AB  - Although the guinea pig is used widely in experimental medical research,
      including in studies on micturition control, the spinal origin of preganglionic
      parasympathetic bladder and somatic external urethral sphincter motoneurons is
      not known. In the male guinea pig using wheat germ agglutinin-conjugated
      horseradish peroxidase and dextran Alexa Fluor 488/568 tracers, preganglionic
      parasympathetic bladder motoneurons were observed in the ventrolateral part of
      the intermediolateral cell group of the first sacral segment. The external
      urethral sphincter motoneurons were found to be located in the ventral horn of
      the first sacral segment, in a cell group corresponding with the nucleus of Onuf
      in cat and human.

PMID- 15147781
TI  - Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant
      effects stronger than those of alpha-tocopherol.
AB  - Crocin is a pharmacologically active component of Crocus sativus L. (saffron)
      used in traditional Chinese medicine. We report here the effects of crocin on
      neuronally differentiated pheochromocytoma (PC-12) cells deprived of
      serum/glucose. Depriving the PC-12 cells of serum/glucose caused peroxidation of
      their cell membrane lipids and decreased intercellular superoxide dismutase (SOD)
      activity. Treating the PC-12 cells with 10 microM crocin inhibited the formation
      of peroxidized lipids, partly restored the SOD activity, and maintained the
      neuron's morphology. These antioxidant effects of crocin were more effective than
      those of alpha-tocopherol at the same concentration. Crocin also suppressed the
      activation of caspase-8 caused by serum/glucose deprivation. These results
      together with our previous data suggest that crocin is a unique and potent
      antioxidant that combats oxidative stress in neurons.

PMID- 15147782
TI  - Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of
      stimulation.
AB  - There is evidence that functionally different areas can be distinguished within
      the nasal mucosa with regard to stimulation site and stimulus properties. The aim
      of the present study was the comparison of electrophysiological and
      psychophysical measures obtained in response to mechanical and chemosomatosensory
      stimulation of two different regions of the nasal mucosa. A total of 40
      volunteers participated in this study (age range 21-36 years). Chemosomatosensory
      event-related potentials (ERPs) were recorded using gaseous CO2 as stimulant,
      while somatosensory ERPs were recorded in response to intranasal mechanical
      stimuli (air puffs). Stimuli were released to the anterior portion and to the
      posterior portion of the nasal cavity. A significant interaction between stimulus
      properties and site of stimulation could be detected after analysis of ERP
      parameters and intensity ratings. Thus, the chemosensory stimulus was perceived
      as stronger in the anterior portion of the nasal cavity whereas this was not the
      case for mechanosensory stimuli. In addition, mechanosensory stimuli were found
      to evoke ERPs with shorter latencies. These results underline the idea that the
      respiratory mucosa should not be seen as a homogeneous tissue. It exhibits
      varying sensitivities to trigeminal stimulation depending on stimulus quality and
      site of stimulation. Hence, perception of chemosensory stimuli seems to be most
      accurate in the anterior portion of the nasal cavity, while sensitivity to
      mechanical stimuli appears to be highest in the posterior portion. In addition,
      these differences within the respiratory mucosa may contribute to differences in
      the perception of orthonasal and retronasal odorous stimulation.

PMID- 15147783
TI  - Reductive activation and thiol reactivity of benzazolo[3,2-a]quinolinium salts.
AB  - Derivatives of benzazolo[3,2-a]quinolium salts (QSDs) are reductively activated
      by the enzymatic reducing agents hypoxanthine (or xanthine)/xanthine oxidase and
      NADH dehydrogenase as evidenced by the increase in rates of ferricytochrome c
      (Cyt(III)c) reduction and oxygen consumption, respectively. No correlation
      between Michaelis-Menten parameters and QSDs redox potentials was found regarding
      anaerobic or aerobic Cyt(III)c reduction, although maximum rates were observed
      for nitro-containing QSDs. However, oxygen consumption rates correlate with QSDs
      redox potentials when NADH dehydrogenase is used as reducing agent. QSDs bind
      covalently to bovine serum albumin (BSA) under anaerobic conditions, in the
      presence, and less in the absence, of HX/XO and only if the nitro group is
      present at the QSD. QSDs react with glutathione (GSH) in the presence of HX/XO
      but not in its absence, under anaerobic conditions. The amount of reacted GSH
      increases, and the relative amount of GSSG formed decreases, with an increase in
      the QSD reduction potential, thus indicating that GSH reacts with reduced nitro
      containing QSDs mainly in a manner which does not involve the production of GSSG,
      presumably, through the formation of the nitroso-QSD-GSH conjugate. QSDs are,
      thus, novel nitro-containing heterocyclic compounds which could be bioreductively
      activated to react with oxygen and thiols.

PMID- 15147784
TI  - Effect of a load of Vitamin A after acute thioacetamide intoxication on dolichol,
      dolichol isoprenoids and retinol content in isolated rat liver cells.
AB  - This study examines how treatment with a single dose of thioacetamide, a known
      experimental hepatotoxin, alters the content of dolichol, dolichol isoprene units
      and retinol in isolated rat parenchymal and non-parenchymal liver cells at
      different times and when the animals are supplemented with Vitamin A.
      Thioacetamide (300 mg/kg i.p.) was administered in a single injection to rats,
      sacrificed at intervals of 0.5, 1, 2, 3, 4, 15 and 30 days. Rats supplemented,
      following thioacetamide, with Vitamin A, 3 days before sacrifice showed increased
      mortality and cellular necrosis on the third and fourth days. Parameters
      indicating tissue necrosis returned to normal values in surviving animals.
      Dolichol and retinol content showed a variable, reversible decrease, with normal
      levels being restored in 15-30 days. After Vitamin A, dolichol content only in
      hepatic stellate cells (HSC) was lower then the controls 3 and 4 days after
      thioacetamide treatment, in parallel with the decrease of retinol storage. The
      percentage of dolichol-18 is not modified by thioacetamide alone. When
      supplemented with Vitamin A the percentage of dolichol-18 always decreased after
      thioacetamide, showing that damage was still present. Mechanisms that might be
      operative in liver cells are briefly discussed. This approach would provide an
      indication to investigate how the length of the dolichol chain is determined.

PMID- 15147785
TI  - Estrogenic activity and estrogen receptor beta binding of the UV filter 3
      benzylidene camphor. Comparison with 4-methylbenzylidene camphor.
AB  - UV filters represent new classes of estrogenic [Environ. Health Perspect. 109
      (2001) 239] or antiandrogenic [Toxicol. Sci. 74 (2003) 43] chemicals. We tested 3
      benzylidene camphor (3-BC), reported as estrogenic in fish [Pharmacol. Toxicol.
      91 (2002) 204], and mammalian systems in comparison to 4-methylbenzylidene
      camphor (4-MBC), shown to be active in rats, and analyzed binding to estrogen
      receptor subtypes. 3-BC and 4-MBC stimulated MCF-7 cell proliferation (EC(50):
      0.68 and 3.9 microM). The uterotrophic assay of 3-BC (oral gavage) in immature
      rats showed unexpected potency with ED50 45.3mg/kg per day; lowest effective dose
      2mg/kg per day, and maximum effect with 70% of ethinylestradiol. After comparing
      with literature data, we found that the oral 3-BC was considerably more potent
      than oral bisphenol A and almost as active as subcutaneous genistein. 3-BC and 4
      MBC displaced 16alpha 125I-estradiol from porcine uterine cytosolic receptors
      (IC(50): 14.5 and 112 microM), and from recombinant human estrogen receptor beta
      (hERbeta) (IC(50): 3-BC, 11.8 microM; 4-MBC, 35.3 microM), whereas no
      displacement was detected at human estrogen receptor alpha (hERalpha) up to 3mM.
      This subtype selectivity makes the two camphor derivatives interesting model
      compounds. Their activity on immature rat uterus is not easily explained by
      ERbeta activation. It cannot be excluded that active metabolites with possibly
      different receptor binding characteristics are formed in vivo.

PMID- 15147786
TI  - Helper T cell subpopulations from women are more susceptible to the toxic effect
      of sodium arsenite in vitro.
AB  - Arsenic is known to produce inhibition as well as induction of proliferative
      responses in animal and human cells depending on the doses. Despite the amount of
      information on the immunotoxic effects of arsenic exposure in different animal
      models, little is known in humans. Arsenic susceptibility of lymphocyte
      subpopulations (T helper (Th), CD4+; T cytotoxic (Tc), CD8+) and whether arsenic
      effects are gender related are still to be determined. This work evaluated the in
      vitro toxicity of sodium arsenite on human T lymphocyte subpopulations from men
      and women. Peripheral blood mononuclear cells (PBMC) obtained from healthy young
      men and women were treated with sodium arsenite (0.01, 0.1, and 1 microM). We
      assessed cell viability, cell proliferation, and the proportion of Th and Tc
      cells after 48 or 72h of arsenic exposure in resting and phytohemagglutinin M
      (PHA)-activated PBMC. We observed that sodium arsenite at 1 microM was more toxic
      for Th than for Tc cells in PBMC from women. Besides, T lymphocytes from women
      were more affected by the cell proliferation inhibition induced by arsenic,
      suggesting that women could be more susceptible to the toxic and immunotoxic
      effects caused by arsenic exposure.

PMID- 15147787
TI  - Estrogen supplementation modulates effects of the endocrine disrupting pollutant
      PCB126 in rat bone and uterus: diverging effects in ovariectomized and intact
      animals.
AB  - The aims of the present study are to compare effects of estrogen depletion (OVX)
      and estradiol (E2) supplementation on the tissue effects of exposure to the
      endocrine disrupting organochlorine 3,3',4,4',5-pentachlorobiphenyl (PCB126). For
      this purpose two highly estrogen-dependent tissues, bone and uterus, were
      studied. Forty rats exposed to PCB126 (ip) for 3 months (total dose 384 microg/kg
      body weight (bw)) were randomized in to OVX/sham operation or E2 supplementation
      (ip, 23 microg/kg, 3 days weekly) per vehicle (corn oil) groups in a 2 x 2
      factorial design. Sham operated rats were treated with vehicle, PCB or PCB plus
      E2 (sham, sham + PCB and sham + PCB + E2, n=10 per group) whereas ovariectomized
      were treated with vehicle, PCB or PCB plus E2(OVX, OVX + PCB and OVX + PCB + E2,
      n=10 per group). As control groups served OVX or sham, and OVX + E2 (n=10 in each
      group). In OVX rats PCB126 + E2 treatment increased trabecular bone volume (TBV)
      (P<0.01), whilst the opposite was found in sham-operated rats (P<0.01). In OVX
      animals exposed to PCB126, E2 supplementation decreased the uterine weight and
      increased the uterine ERbeta mRNA level, whilst no difference was found between
      the PCB126 and PCB126 + E2 exposed groups in the sham-operated animals. In
      conclusion, estrogen modulates PCB126 induced effects on trabecular bone, as well
      as several uterine parameters. These results further support an important role of
      estrogen on the toxic effects of PCB126 on bone and uterus.

PMID- 15147788
TI  - Flow-cytometric analysis on adverse effects of polysorbate 80 in rat thymocytes.
AB  - The effects of polysorbate 80, a non-ionic surfactant widely used in
      pharmaceutical products, on rat thymocytes were examined to reveal its toxic
      property at the cellular level. Polysorbate 80 at concentrations of 1-100
      microg/ml did not significantly affect the cell viability. This surfactant at 30
      microg/ml or more augmented the intensity of fluo-3 fluorescence, indicating the
      increase in intracellular Ca(2+) concentration. Such an augmentation of fluo-3
      fluorescence by polysorbate 80 was not seen under the Ca(2+)-free condition,
      suggesting that polysorbate 80 increased membrane Ca(2+) permeability. The
      concentration-dependent polysorbate 80 at 10 microg/ml or more attenuated the
      intensity of 5-chloromethylfluorescein, indicating a decrease in cellular content
      of glutathione by polysorbate 80. Furthermore, the agent at 1 microg/ml or more
      attenuated the intensity of bis-(1,3-dibutylbarbituric acid) trimethine oxonol
      fluorescence, being independent from the changes in membrane potential. This
      phenomenon indicates that polysorbate 80 at 1 microg/ml or more may attenuate the
      incorporation of anionic compounds into the membranes. It can be suggested that
      polysorbate 80 modifies some of membranes and intracellular physiological
      parameters without affecting the cell viability.

PMID- 15147790
TI  - Hippocampal and striated skeletal muscle changes in fatty acid composition
      induced by ethanol in alcohol-preferring rats.
AB  - Chronic ethanol intake affects various organ systems of the body. The present
      study evaluated modifications of fatty acid concentrations both in brain and
      striated skeletal muscles of rats genetically selected for voluntary high ethanol
      intake. Three groups of rats were tracked for 10 weeks of access to ethanol only
      as fluid (group 1) to free choice of ethanol and water (group 2) or to water only
      (group 3). At the end of the period, the animals were sacrificed and their brain
      hippocampus and striated skeletal muscles were removed and fatty acid content of
      these tissues was determined. Long-chain fatty acid content increased in the
      hippocampus while it decreased in the striated skeletal muscles. Short chain
      fatty acid content decreased in the hippocampus while short chain fatty acid
      content increased in the striated skeletal muscles. The data show that brain and
      striated skeletal muscles differently modulate fatty acid content perhaps because
      these areas utilize different cell membrane functionality regulation systems.

PMID- 15147789
TI  - Comparison of anti-androgenic activity of flutamide, vinclozolin, procymidone,
      linuron, and p, p'-DDE in rodent 10-day Hershberger assay.
AB  - The rodent Hershberger assay proposed by the Organization for Economic Co
      operation and Development (OECD) is in the process of the validating a test
      method to detecting the androgenic or anti-androgenic compounds. The aim of this
      study was to compare the anti-androgenic properties of flutamide, vinclozolin,
      procymidone, linuron, and p,p'-DDE in a 10-day Hershberger assay. In the present
      study, we used immature Sprague-Dawley male rats castrated at 6 weeks of age.
      Testosterone propionate (TP) was subcutaneously injected for 10 consecutive days
      at doses of 0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg per day. To compare the anti
      androgenic activity of test compounds, flutamide (1, 5, 10, or 20 mg/kg per day),
      a pure androgen antagonist was used as a positive control, and administered by
      oral gavage after TP (0.4 mg/kg per day) treatment. In addition, vinclozolin (25,
      50, or 100 mg/kg per day), procymidone (25, 50, or 100 mg/kg per day), linuron
      (25, 50, or 100 mg/kg per day), and p,p '-DDE (25, 50, or 100 mg/kg per day) were
      also administered by oral gavage after TP (0.4 mg/kg per day) treatment. As
      expected, TP dose-dependently increased accessory sex organ weights, and
      statistically significant effects were observed at doses of 0.1 (only seminal
      vesicles) or 0.2mg/kg per day and above. Serum testosterone levels increased
      significantly at 0.4 mg/kg per day and above, while serum LH levels were
      decreased in a dose-dependent manner. Flutamide significantly inhibited the TP
      induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus
      bulbocavernosus muscles (LABC) at 1mg/kg per day and above, and Cowper's glands
      and glans penis at 5mg/kg per day and above. In contrast to accessory sex organ
      weights, flutamide did not affect the serum testosterone levels compared to the
      control at any concentration, but serum LH levels were significantly increased at
      doses of 10 and 20 mg/kg per day. Similar to flutamide, vinclozolin caused a
      statistically significant decrease in the weights of seminal vesicles (to 65 and
      40% of the control), ventral prostate (to 66 and 51% of the control), LABC (to 81
      and 66% of the control), and Cowper's glands (to 81 and 65% of the control) at 50
      and 100 mg/kg per day, respectively. Glans penis weight was also significantly
      reduced (to 79% of the control), but only at 100 mg/kg per day. The most
      pronounced effects were observed in the procymidone treatment groups. Procymidone
      significantly inhibited TP-induced re-growth of accessory sex organs at 25mg/kg
      per day and above, whereas glans penis weight significantly decreased (to 69% of
      the control), but only at 100 mg/kg per day. Linuron also inhibited TP-induced re
      growth of the seminal vesicles (to 72 and 53% of the control), ventral prostate
      (to 75 and 62% of the control), Cowper's glands (to 74 and 61% of the control) at
      50 and 100 mg/kg per day, respectively. LABC (to 65% of the control) and glans
      penis (to 80% of the control) weights were significantly reduced, but only at 100
      mg/kg per day. In case of p,p'-DDE, seminal vesicle weights were significantly
      decreased at 50 (to 66% of the control) and 100 mg/kg per day (to 58% of the
      control). In addition, ventral prostate (to 79% of the control), LABC (to 75% of
      the control), and Cowper's gland (to 82% of the control) weights were reduced,
      but only at 100 mg/kg per day. On the contrary, no statistically significant
      differences in serum testosterone or LH levels were observed versus the control.
      p,p'-DDE significantly increased liver weight in a dose-dependent manner, without
      affecting on body weights. Our results indicate that procymidone may act as a
      stronger androgen receptor (AR) antagonist than vinclozolin, linuron, or p,p'
      DDE. We conclude that the 10-day Hershberger assay is a sensitive method for
      detecting potential anti-androgenic compounds.

PMID- 15147791
TI  - Interactions in the tumor-promoting activity of carbon tetrachloride,
      trichloroacetate, and dichloroacetate in the liver of male B6C3F1 mice.
AB  - Interactions between carcinogens in mixtures found in the environment have been a
      concern for several decades. In the present study, male B6C3F1 mice were used to
      study the responses to mixtures of dichloroacetate (DCA), trichloroacetate (TCA),
      and carbon tetrachloride (CT). TCA produces liver tumors in mice with the
      phenotypic characteristics common to peroxisome proliferators. DCA increases the
      growth of liver tumors with a phenotype that is distinct in several respects from
      those produced by TCA. These chemicals are effective as carcinogens at doses that
      do not produce cytotoxicity. Thus, they encourage clonal expansion of initiated
      cells through subtle, selective mechanisms. CT is well known for its ability to
      promote the growth of liver tumors through cytotoxicity that produces a
      generalized growth stimulus in the liver that is reflected in a reparative
      hyperplasia. Thus, CT is relatively non-specific in its promotion of initiated
      cells within the liver. The objective of this study was to determine how the
      differing modes of action of these chemicals might interact when given as mixed
      exposures. The hypothesis was that the effects of two selective promoters would
      not be more than additive. On the other hand, CT would be selective only to cells
      not sensitive to its effects as a cytotoxin. Thus, it was hypothesized that
      neither DCA nor TCA would add significantly to the effects produced by CT. Mice
      were initiated by vinyl carbamate (VC), and then promoted by DCA, TCA, CT, or the
      pair-wised combinations of the three compounds. The effect of each treatment or
      treatment combination on tumor number per animal and mean tumor volume was
      assessed in each animal. Dose-related increases in mean tumor volume were
      observed with 20 and 50mg/kg CT, but each produced equal numbers of tumors at 36
      weeks. As the dose of CT was increased to >/=100mg/kg substantial increases in
      the number of tumors per animal were observed, but the mean tumor size decreased.
      This finding suggests that initiation occurs as doses of CT increase to
      >/=100mg/kg, perhaps as a result of the inflammatory response that is known to
      occur with high doses of CT. When administered alone in the drinking water at
      0.1, 0.5 and 2g/l, DCA increased both tumor number and tumor size in a dose
      related manner. With TCA treatment at 2g/l in drinking water a maximum tumor
      number was reached by 24 weeks and was maintained until 36 weeks of treatment.
      DCA treatment did not produce a plateau in tumor number within the experimental
      period, but the numbers observed at the end of the experimental period were
      similar to TCA and doses of 50mg/kg CT. The tumor numbers observed at the end of
      the experiment are consistent with the assumption that the administered dose of
      the tumor initiator, vinyl carbamate, was the major determinant of tumor number
      and that treatments with CT, DCA, and TCA primarily affected tumor size. The
      results with mixtures of these compounds were consistent with the basic
      hypotheses that the responses to tumor promoters with differing mechanisms are
      limited to additivity at low effective doses. More complex, mutually inhibitory
      activity was more often observed between the three compounds. At 24 weeks, DCA
      produced a decrease in tumor numbers promoted by TCA, but the numbers were not
      different from TCA alone at 36 weeks. The reason for this result became apparent
      at 36 weeks of treatment where a dose-related decrease in the size of tumors
      promoted by TCA resulted from DCA co-administration. On the other hand, the low
      dose of TCA (0.1g/l) decreased the number of tumors produced by a high dose of
      DCA (2g/l), but higher doses of TCA (2g/l) produced the same number as observed
      with DCA alone. DCA inhibited the growth rate of CT-induced tumors (CT dose =
      50mg/kg). TCA substantially increased the numbers of tumors observed at early
      time points when combined with CT, but this was not observed at 36 weeks. The
      lack of an effect at 36 weeks was attributable to the fact that more than 90% of
      the livers consisted of tumors and the earlier effect was masked by coalescence
      of tumors. Thus, the ability of TCA to significantly increase tumor numbers in CT
      treated mice was probably real and contrary to our original hypothesis that CT
      was non-specific in its effects on initiated cells. It is probable that the
      interaction between CT and TCA is explained through stimulation of the growth of
      cells with differing phenotypes. These data suggest that the outcome of
      interactions between the mechanisms of tumor promotion vary based on the
      characteristics of the initiated cells. The interactions may result in additive
      or inhibitory effects, but no significant evidence of synergy was observed.

PMID- 15147792
TI  - Ochratoxin A and beta2-microglobulinuria in healthy individuals and in chronic
      interstitial nephropathy patients in the centre of Tunisia: a hot spot of
      Ochratoxin A exposure.
AB  - Ochratoxin A (OTA) is a nephrotoxic mycotoxin considered to be the causal agent
      of the Balkan endemic nephropathy (BEN). In Tunisia, a chronic interstitial
      nephropathy (CIN) of unknown aetiology, resembling BEN, has been characterised
      wherein OTA seems to be implicated too. However, despite the considerable number
      of investigations conducted so far, the role of OTA in the outcome of this human
      nephropathy is still uncertain. In this study, an attempt is being made to
      consolidate the link between OTA and the Tunisian CIN of unknown aetiology. Blood
      OTA and beta(2)-microglobulinuria levels were measured in several groups of
      healthy individuals and patients having different renal diseases of known and
      unknown aetiologies (100 nephropathy patients and 40 healthy subjects). The high
      blood OTA and beta(2)-microglobulinuria levels seem to be strongly associated to
      the CIN of unknown aetiology. Our results support the involvement of this
      nephrotoxic agent in the outcome of this particular human nephropathy and
      underline furthermore the importance of beta(2)-microglobulinuria in the
      characterization of this disease.

PMID- 15147793
TI  - Biochemical changes in mouse lung after subcutaneous injection of the sulfur
      mustard 2-chloroethyl 4-chlorobutyl sulfide.
AB  - Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in
      World War I which continues to be produced, stockpiled, and occasionally deployed
      by some countries, and could be used potentially by terrorists. Exposure to HD
      can cause erythema, blisters, corneal opacity, and airway damage. We have
      reported previously that subcutaneous (SC) injection of immunodeficient athymic
      nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic
      biochemical changes in several organs distal to the exposure site. In the present
      study, we examined the response of non-immunodeficient Swiss Webster mice to the
      mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found
      that a single SC injection of 20-25 microl/mouse causes death within 24h.
      Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat
      CECBS or an equal volume of saline as control. We examined the lungs after 1, 24,
      and 48 h for biochemical changes including total and oxidized glutathione,
      protein, DNA, and lipid peroxidation contents in tissue homogenate, and
      superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and
      glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we
      found statistically significant changes that were resolved by 48 h. These changes
      mimicked those of HD and BCS and were generally consistent with free radical
      mediated oxidative stress. The implications of these observations are two-fold.
      First, dermal exposure to low-dose mustard gas could elicit systemic changes
      impacting distal organs such as the lungs. It also suggests that antioxidants
      could potentially modulate the response and reduce the damage. Second, although
      the use of known CWAs such as HD is prohibited, analogs that are not recognized
      as agents are as toxic and could be dangerous if acquired and used by potential
      terrorists.

PMID- 15147794
TI  - Isolation and characterisation of a cytotoxic polyunsaturated aldehyde from the
      marine phytoplankter Phaeocystis pouchetii (Hariot) Lagerheim.
AB  - Several investigators have documented that the marine phytoplankter Phaeocystis
      pouchetii produce and excrete some compound that has adverse effects on its
      surroundings, but the chemical composition and structure of the active agent has
      so far been unknown. In the present study we used mass spectrometry to
      investigate the structural properties of the putative toxin. Colonial cells of P.
      pouchetii were collected along the coast of northern Norway and cultivated in the
      lab for a limited period of time prior to harvesting by filtration. Harvested
      cells and culture filtrate were extracted separately with organic solvents, and a
      yeast cell bioassay was used to track the toxic fractions during extraction and
      purification with HPLC. We found the organic extract from the culture filtrate to
      be toxic, and after purification with RP-HPLC the cytotoxic activity was
      recovered as one fraction. When the toxic fractions were pooled and analysed by
      GC-MS we were able to identify 2-trans-4-trans-decadienal by comparing retention
      time and fragmentation pattern to a commercial standard. This is the first report
      of a polyunsaturated aldehyde produced by a marine alga belonging to the class
      Haptophyceae, and this implies that production and release of these reactive
      compounds are not limited to diatoms.

PMID- 15147795
TI  - Chlropyrifos-methyl shows anti-androgenic activity without estrogenic activity in
      rats.
AB  - Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain
      storage and agriculture, has been suspected as endocrine disrupter by a few in
      vitro studies. This study was performed to investigate the (anti-) estrogenicity
      and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay
      and rat Hershberger assay. CPM with or without 17beta-estradiol were administered
      to 20 days old female rats to investigate its (anti-) estrogenic activity.
      Uterine and vaginal weight, uterine epithelial cell height were not affected by
      the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative
      vagina weight in 17beta-estradiol treated immature female rats without any
      changing of uterine weight. Relative liver weight was increased with decrease of
      body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with
      bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with
      or without testosterone propionate were administered to castrated rat of 51 days
      old for 10 days to investigate the (anti-)androgenic activity,. The weight of
      relative and absolute androgen-dependent accessory sex organs; seminal vesicle
      with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP),
      levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were
      unchanged by the treatment of CPM alone. While CPM induced the increase of
      relative adrenal gland weight, CPM 50mg/kg decreased the weights of CV/CG, VP, CG
      and LABC without change of GP without changing of GP when it was treated with TP.
      In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in
      immature female rats, but it represents anti-androgenic activity by inhibition of
      the TP-stimulated increase of the weight of accessory sex organs.

PMID- 15147796
TI  - Modulation of cytochrome P450 1A1 by food-derived heterocyclic aromatic amines.
AB  - A short-term effect of a meal of fried meat is a postprandial induction of
      hepatic and intestinal cytochrome P450 activity. In order to identify the
      components responsible for this effect we investigated the potency of food
      derived genotoxic heterocyclic aromatic amines (HA) to induce CYP1A1 in vitro. In
      two cell lines, the rat hepatoma cell line H4IIE and the human breast cancer cell
      line MCF-7, we investigated 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
      (MeIQx), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAC), 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) and Harman representing the different classes of HA
      at concentrations from 10(-8) to 10(-4) M. Induction of CYP1A1 was analysed on
      the mRNA level by semi-quantitative RT-PCR and the protein level (western blot
      using specific antibodies). The relative order of enzyme induction was Trp-P-1
      with 1.4 x 10(-6) M (EC50 compared to TCDD 10(-9) M), MeAalphaC (1.4 x 10(-5)),
      Harman (2.1 x 10(-4)) and MeIQx (1.0 x 10(-3)). Furthermore, CYP1A1 enzyme
      activity was analysed as ethoxyresorufin-O-deethylase. While protein and mRNA
      analyses gave similar results, competitive inhibition impaired the enzyme
      activity assay. Inhibition of CYP1A1 activity was determined using microsomes of
      heterologous expressed CYP1A1. This dose-dependent inhibitory activity paralleled
      the induction potency. These results compare well with earlier data published for
      hepatic enzyme induction by HA observed in animal experiments. However, since the
      observed activities are rather weak and the amounts of HA ingested with a meal
      are low, there may be other factors involved in the observed postprandial enzyme
      induction in humans. On the other hand, concentrations in the micromolar range
      that are reached in high dosage animal experiments with HA may well influence
      cytochrome activity and, thus, influence the experimental outcome of these
      studies.

PMID- 15147797
TI  - Metallothionein is induced and trace element balance changed in target organs of
      a common viral infection.
AB  - In experimental studies on the common human coxsackievirus B type 3 (CB3)
      infection, administered cadmium (Cd) is known to accumulate in the liver and
      kidneys. CB3 adapted to Balb/c mice was used to study whether infection affects
      the Cd-binding protein, metallothionein (MT) and if this alters the normal
      physiological trace element balance in the liver, kidney, spleen and brain. On
      day 3 of infection, degradation of liver proteins (44%, P<0.01) occurred, whereas
      in the spleen, protein increased (63%, P<0.05). The infection increased MT five
      fold (P<0.01) in liver and kidneys, and in spleen by 34% (P<0.05). A
      redistribution of Cd and copper (Cu) from the liver to the kidney was associated
      with this increase in MT, resulting in an increased (P<0.01) kidney/liver ratio
      for both elements. The infection increased the zinc (Zn) concentration more in
      the kidney than in the liver, but the kidney/liver ratio was not significantly
      affected. Results show that MT is increased in several organs during the early
      phase of infection and is associated with redistribution of both essential and
      non-essential trace elements. This may be a normal response in common infections
      that could adversely influence the pathogenesis when the host is concomitantly
      exposed to potentially toxic trace elements, even at levels in the physiological
      range.

PMID- 15147798
TI  - Ochratoxin A and some of its derivatives modulate radical formation of porcine
      blood monocytes and granulocytes.
AB  - Modulating effects of ochratoxin A (OTA) and some of its derivatives on viability
      and oxidative burst activity of porcine monocytes and granulocytes have been
      studied. The formation of free oxygen radicals by monocytes was suppressed by OTA
      and ochratoxin C (OTC) at concentrations between 10 and 1000 ng/ml. Intracellular
      radical formation of granulocytes was in part already significantly reduced at 1
      ng/ml of these mycotoxins. Conversely, the intracellular formation of radicals in
      monocytes of individual pigs was stimulated by the toxins at 1-100 ng/ml. A
      biologically active fraction of the crude toxin (RE2) which had been identified
      as OTC had a stronger effect than all other derivatives of ochratoxin A. Whether
      these modulating effects of OTA and OTC on phagocyte functions are of
      significance in the pathogenesis of infectious diseases, needs to be studied in
      more detail. In this context, the occurrence of OTC in food and feeds should be
      examined more closely.

PMID- 15147800
TI  - Strategies for enhancing the immunostimulatory effects of CpG
      oligodeoxynucleotides.
AB  - Synthetic oligodeoxynucleotides (ODN) containing CpG sequences are recognized as
      a "danger" signal by the immune system of mammals. As a consequence, CpG ODN
      stimulate innate and adaptive immune responses in humans and a variety of animal
      species. Indeed, the potential of CpG ODN as therapeutic agents and vaccine
      adjuvants has been demonstrated in animal models of infectious diseases, allergy
      and cancer and are currently undergoing clinical trials in humans. While CpG ODN
      are potent activators of the immune system, their biologic activity is often
      transient, subsequently limiting their therapeutic application. Modifications in
      the CpG ODN backbone chemistry, various delivery methods including mixing or
      cross-linking of ODN to other carrier compounds have been shown to significantly
      enhance the biologic activity of ODN. However, the exact mechanisms that mediate
      this enhancement of activity are not well understood and may include local cell
      recruitment and activation, cytokine production, upregulation of receptor
      expression and increasing the half-life of ODN through creation of a depot. We
      will review the various approaches that have been used in enhancing the
      immunostimulatory effects of CpG ODN in vivo and also discuss the possible
      mechanisms that may be involved in this enhancement.

PMID- 15147801
TI  - Formulation development of inhalation powders for FK888 with carrier lactose
      using Spinhaler and its absorption in healthy volunteers.
AB  - (4R)-4-Hydroxy-l-[(l-methyl-lH-indol-3-yl)carbonyl]-L-prolyl-N-benzyl-N-methyl-3
      (2-naphthyl)-L-alaninamide (FK888) is a candidate selective NK1 receptor
      antagonist, and it exhibits poor absorption from the gastrointestinal (GI) tract
      in healthy volunteers. The objective of this study was to develop an optimized
      DPI formulation with carrier lactose using a Spinhaler, and thereby improve the
      systemic absorption of FK888. The fine particles of FK888 were blended with
      various carrier lactoses, and in vitro deposition properties were investigated
      using a twin impinger. The mixture using 100 M and 325 M lactoses [Sieved
      lactoses (SLs)] exhibited a higher emitted dose (Em) than 200 M, 450 M and
      micronized lactoses [Milled lactoses (MLs)]. The flowability of carrier lactose
      had an influence on the Em. On the other hand, the respirable particle (RP)
      fraction in the formulations with MLs was much higher than that of SLs, in spite
      of the blended ratios of lactose. It was also observed that the mixture of 325 M
      with the micronized lactose particles had the same RP as 200 M, although the 325
      M alone had a low RP. Considering the Em and RP obtained, we chose 200 M for
      FK888 dry powder inhaler (DPI). The proportional absorption was found up to the
      12.5% of the FK888 ratio (5 mg as unit dose) for the Cmax and AUC in healthy
      volunteers. In conclusion, 200 M, which has fine lactose particles and a better
      flowability than other MLs, is an extremely suitable carrier for maximizing the
      fine particle dose as far as FK888 is concerned. Furthermore, an improvement in
      the systemic absorption of FK888 was achieved using the dry powder formulations.

PMID- 15147799
TI  - The ex vivo study of synergistic effects of polycyclic aromatic hydrocarbon,
      benzo(a)pyrene with ovalbumin on systemic immune responses by oral route.
AB  - The present study was undertaken in order to examine whether oral administration
      of soluble antigen together with one of polycyclic aromatic hydrocarbons (PAHs)
      which is present in diesel exhaust particles (DEPs) called benzo(a)pyrene (BP),
      induced the systemic immune response in mice or not. Mice were orally given 1mg
      of ovalbumin (OA), a common food allergen, every 3 days over a period of 15 days.
      The results showed that oral administration of OA plus BP produced anti-OA IgE
      antibodies in serum, whereas either OA or BP alone failed to show the antigen
      specific IgE antibody production. Production of anti-OA IgE antibody, which is
      dependent on Th2 CD4(+) T cells, was seen in mice fed with combined OA and BP was
      significantly higher than that of other groups. The anti-OA antibody production
      was associated with marked secretion of the Th1 cytokines, IFN-gamma and IL-12p70
      as well as the Th2 cytokines IL-4, and IL-10. These results suggest that BP may
      act as a mucosal adjuvant in the gut enhancing systemic Th1 and Th2 immune
      responses and might play a role in oral immunization and food allergy.

PMID- 15147802
TI  - Pharmaceutical design of a novel colon-targeted delivery system using two-layer
      coated tablets of three different pharmaceutical formulations, supported by
      clinical evidence in humans.
AB  - Drug delivery systems to the colon are being actively investigated in order to
      develop oral preparations of peptides and treat local colonic diseases. However,
      it is difficult to ensure that an oral preparation disintegrates specifically in
      the human colon. To make a colonic delivery system practical for medical use, in
      vitro testing methods need to be established in order to determine the
      specifications of the preparations. To achieve this objective, three
      pharmaceutical preparations, designed to have different tablet disintegration
      times, were used to examine three buffers in seven combinations intended to
      simulate pH changes in the stomach, small intestine, and colon of humans. To
      validate the in vitro methodology, furthermore, the fate of all the formulations
      was examined in the gastrointestinal (GI) tract of healthy volunteers. A three
      way crossover trial by scintigraphy revealed that the three formulations--in
      spite of presenting different in vitro tablet disintegration profiles--have
      comparable transit profiles and excellent colon-targeting properties in the human
      gastrointestinal tract regardless of gender and age. These facts strongly suggest
      that this novel delivery system may be useful for the delivery of drugs to the
      human colon.

PMID- 15147803
TI  - Control of pore size and permeability of a glucose-responsive gating membrane for
      insulin delivery.
AB  - The pore size and permeability control of a glucose-responsive gating membrane
      with plasma-grafted poly(acrylic acid) (PAAC) gates and covalently bound glucose
      oxidase (GOD) enzymes were investigated systematically. The PAAC-grafted porous
      polyvinylidene fluoride (PVDF) membranes with a wide range of grafting yields
      were prepared using a plasma-graft pore-filling polymerization method, and the
      immobilization of GOD was carried out by a carbodiimide method. The linear
      grafted PAAC chains in the membrane pores acted as the pH-responsive gates or
      actuators. The immobilized GOD acted as the glucose sensor and catalyzer; it was
      sensitive to glucose and catalyzed the glucose conversion to gluconic acid. The
      experimental results showed that the glucose responsivity of the solute
      diffusional permeability through the proposed membranes was heavily dependent on
      the PAAC grafting yield, because the pH-responsive change of pore size governed
      the glucose-responsive diffusional permeability. It is very important to design a
      proper grafting yield for obtaining an ideal gating response. For the proposed
      gating membrane with a PAAC grafting yield of 1.55%, the insulin permeation
      coefficient after the glucose addition (0.2 mol/l) was about 9.37 times that in
      the absence of glucose, presenting an exciting result on glucose-sensitive self
      regulated insulin permeation.

PMID- 15147804
TI  - Synergistic penetration enhancement effect of ethanol and phospholipids on the
      topical delivery of cyclosporin A.
AB  - In the present study, ethanol was used with a commercially available lipid
      mixture, NAT 8539, to improve the topical delivery of cyclosporin A (CyA). The
      vesicles formed from this solution ranged from 56.6 to 100.6 nm in diameter,
      depending on the amount of ethanol added in the formulation. In-vitro skin
      penetration studies were carried out with Franz diffusion cell using human
      abdominal skin. There was a decrease in average size of vesicles, as the amount
      of ethanol in formulation increased from 0% to 3.3% and a further addition of
      ethanol resulted in an increase in average diameter of vesicles. CyA vesicles
      containing 10% and 20% ethanol showed statistically enhanced deposition of CyA
      into the stratum corneum (SC), as compared to vesicles prepared without ethanol.
      CyA vesicles prepared with NAT 8539/ethanol (10/3.3) showed a 2.1-fold, CyA
      vesicles with NAT 8539/ethanol (10/10) showed a 4.4-fold, and CyA vesicles with
      NAT 8539/ethanol (10/20) showed a 2.2-fold higher deposition of CyA into SC, as
      compared to vesicles made of NAT 8539 without ethanol [NAT 8539/ethanol (10/0)].
      The efficiency of the formulations was sequenced in the order of: NAT
      8539/ethanol (10/10)>NAT 8539/ethanol (10/20)>NAT 8539/ethanol
      (10/3.3)>ethanol>NAT 8539/ethanol (10/0). These results can be considered a step
      forward for the topical delivery of problematic molecules like CyA using
      liposomes as a tool for the treatment of inflammatory skin diseases like
      psoriasis, atopic dermatitis, and diseases of the hair follicle like alopecia
      areata, etc.

PMID- 15147805
TI  - Continuous release of rh-interferon alpha-2a from triglyceride matrices.
AB  - The use of biodegradable polymeric matrices as controlled release systems is
      known to be associated with various drawbacks. The objective of this study was to
      develop an alternative delivery system based on triglycerides, thereby aiming for
      sustained continuous protein release. Tristearin implants containing lyophilised
      rh-interferon alpha-2a (IFN-alpha) and varying amounts of polyethylene glycol
      6000 (PEG) were prepared by compression. Release studies exhibited that more than
      90% of the incorporated IFN-alpha can be liberated in a continuous way over 1
      month from systems containing 10% PEG. Integrating hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) into the matrices proved to stabilise IFN-alpha and led
      to a higher and faster protein release due to solubilising effects. The protein
      was released in virtually monomeric form. Scanning electron microscopy (SEM) and
      mercurial porosimetry revealed the matrices forming an interconnected pore
      network.

PMID- 15147806
TI  - In vivo and in vitro evaluation of three controlled release principles of 6-N
      cyclohexyl-2'-O-methyladenosine.
AB  - 6-N-Cyclohexyl-2'-O-methyladenosine was formulated into controlled release
      formulations exhibiting comparable in vitro release profiles using different
      formulation principles, i.e. osmotic pump tablets, membrane-coated pellets and
      hydrophilic matrix tablet. Dissolution behaviour of these formulations was
      evaluated in vitro under various testing conditions to assess the effect of pH
      and hydrodynamic conditions. It was found that osmotic tablets were not sensitive
      to dissolution media pH and hydrodynamics change, while drug release from
      monolithic hydrophilic matrix tablets were pH-dependent. When tested in vivo in
      dogs, it was found that metabolism of 6-N-Cyclohexyl-2'-O-methyladenosine was
      extensive and appeared to be saturable based on a pharmacokinetic study.
      Cumulative percent input in vivo (%dose) was obtained by numerical deconvolution,
      and compared to in vitro release profiles. A linear correlation between fraction
      absorbed (FRA) in vivo and fraction dissolved (FRD) in vitro was established for
      osmotic tablets--a true zero-order release formula, whereas only a nonlinear
      correlation was obtained for membrane-coated pellets. The difference in the in
      vivo behaviour of these formulations, despite their similar in vitro release
      characteristics, demonstrated the effect of different controlled release
      principles on their in vivo bioavailability. The curvature of fraction absorbed
      in vivo vs. fraction dissolved in vitro for membrane-coated pellets indicated
      that there was a time-scale difference between in vivo and in vitro testing. In
      conclusion, drug release from the osmotic system was independent of in vitro and
      in vivo conditions, where best sustained release effect was achieved, whereas the
      in vitro dissolution test employed for membrane-coated pellets and hydrophilic
      matrix tablets needed to be optimized to be biorelevant.

PMID- 15147807
TI  - Formulation optimization of water-in-oil-water multiple emulsion for intestinal
      insulin delivery.
AB  - Formulation optimization of the water-in-oil-in-water multiple emulsion
      incorporating insulin was performed based on statistical methods such as the
      orthogonal experimental design and the response surface evaluation. As model
      formulations, 16 types of emulsions were prepared according to the orthogonal
      experimental design. To optimize the formulation, the influence of causal factors
      such as amounts of gelatin, insulin, oleic acid (OA) and the volume ratio of the
      outer aqueous phase to total and agitation time of the second emulsification
      process on individual characteristics of the emulsion, such as inner droplet
      size, viscosity, stability and pharmacological effect, was evaluated first. Based
      on the analysis of ANOVA, it was concluded that the droplet size of the emulsion
      was influenced by the volume ratio of the outer aqueous phase significantly. The
      viscosity of the emulsion was affected by these causal factors and their
      interactions; however, the most predominant contribution of all causal factors
      was the volume ratio of the outer aqueous phase. Similarly, one of the most
      important characteristics in the design of the formulation, stability, was
      affected by the causal factors. With regard to the hypoglycemic effect, the most
      influential factor was the content of OA in the emulsion. By means of a novel
      optimization technique involving a multivariate spline interpolation (MSI),
      formulation optimization was performed with respect to pharmacological effect and
      stability, and the optimum formulation with a desirable pharmacological effect
      and high stability was successfully estimated.

PMID- 15147808
TI  - Antitumor characteristics of methoxypolyethylene glycol-poly(DL-lactic acid)
      nanoparticles containing camptothecin.
AB  - The novel nanoparticles (CPT-NP) were prepared by the solvent evaporation method
      using methoxypolyethylene glycol-poly(DL-lactic acid) block copolymer as a matrix
      and camptothecin (CPT) as an antitumor agent, and the antitumor characteristics
      were examined in vitro and in vivo. The mean diameter of CPT-NP was approximately
      250 nm. The drug release from CPT-NP in phosphate-buffered saline, pH 7.4,
      depended on the particle concentration; in the diluted condition, the initial
      rapid release was greater and subsequent gradual release was faster. After i.v.
      administration (0.5 mg CPT eq./kg) in rats, CPT-NP showed a longer plasma
      retention than CPT solution. In both single (2.5 mg CPT eq./kg) and double (2.5
      mg CPT eq./kg x 2) administration to mice bearing sarcoma 180 solid tumor, CPT-NP
      were much more effective than CPT solution; especially, the tumor disappeared
      completely in three of the four mice in twice administration of CPT-NP, when the
      body weight did not decrease markedly. After i.v. administration to the tumor
      bearing mice, CPT-NP showed better plasma retention, and high and long tumor
      localization. CPT-NP are suggested to greatly improve the efficacy of CPT due to
      their pharmacokinetic features.

PMID- 15147809
TI  - Mucosal insulin delivery systems based on complexation polymer hydrogels: effect
      of particle size on insulin enteral absorption.
AB  - Insulin-loaded polymer (ILP) microparticles composed of poly(methacrylic acid)
      and poly(ethylene glycol), which have pH-dependent complexation and mucoadhesive
      properties have been thought to be potential carriers for insulin via an oral
      route. Nevertheless, further optimization of the polymer delivery system is
      required to improve clinical application. Therefore, the effect of particle size
      of the ILP (L-ILP: 180-230 microm, S-ILP: 43-89 microm, SS-ILP: <43 microm) on
      insulin absorption was studied in the in situ loop system, hypothesizing smaller
      particle sizes of ILP could induce bigger hypoglycemic effects due to increase
      mucoadhesive capacity. To verify the hypothesis, the adhesive capacities of
      differently sized ILPs to the mucosal tissues were evaluated. Additionally, the
      intestinal site-specificity of ILP for insulin absorption was investigated. Intra
      and inter-cellular integrity and/or damage were also examined by lactate
      dehydrogenase leakage and membrane electrical resistance change to ensure the
      safety of ILP as a carrier for oral route. As hypothesized, the smaller sized
      microparticles (SS-ILP) showed a rapid burst-type insulin release and higher
      insulin absorption compared with the microparticles having larger sizes,
      resulting in greater hypoglycemic effects without detectable mucosal damage. In
      fact, SS-ILP demonstrated higher mucoadhesive capacity to the jejunum and the
      ileum than those of L-ILP. Moreover, SS-ILP's enhancement effect of insulin
      mucosal absorption showed a site-specificity, demonstrating maximum effect at the
      ileal segment. These results imply that the particle size and delivery site are
      very important factors for ILP with respect to increasing the bioavailability of
      insulin following oral administration.

PMID- 15147810
TI  - Mesoporous SBA-15 HPLC evaluation for controlled gentamicin drug delivery.
AB  - Mesoporous silica SBA-15 was prepared to evaluate its application as gentamicin
      drug delivery system. Two procedures were used to evaluate the delivery: calcined
      powder and disk conformed. The samples were charged with gentamicin sulphate and
      the experiments were carried out in vitro. No significant difference between
      powder and disk was observed in the tests. The release profiles exhibited a
      pronounced initial burst release effect of 60%, followed by a very slow release
      pattern. A new HPLC method was employed for calculated gentamicin amount in the
      delivery test. This method requires a small amount of sample, very advisable in
      these kinds of assays.

PMID- 15147811
TI  - Hepatic uptake of negatively charged particles in rats: possible involvement of
      serum proteins in recognition by scavenger receptor.
AB  - The mechanisms involved in the hepatic uptake of negatively charged carboxylated
      polystyrene nanospheres with a size of 50 nm (CNS-50) were examined in rats. The
      liver perfusion experiments revealed that hepatic disposition of CNS-50 in the
      absence of serum could be partially ascribed to the direct recognition of the
      surface negative charge by scavenger receptors. On the other hand, the apparent
      negative charge of CNS-50 surface dramatically reduced in the presence of serum,
      because the adsorption of serum protein on their surface results in masking their
      intrinsic negative charge. However, hepatic disposition of CNS-50 in the presence
      of serum was significantly inhibited by poly inosinic acid (poly I), a typical
      inhibitor for scavenger receptors, and the extent of inhibition by poly I was
      even larger than that in the absence of serum, suggesting that the serum proteins
      associated on CNS-50 surface could be recognized by scavenger receptors. These
      results indicate that not only the intrinsic negative charge but also serum
      proteins associated on the surface play an important role in hepatic uptake of
      negatively charged particles via scavenger receptors.

PMID- 15147812
TI  - The effect of poly(ethylene glycol) molecular architecture on cellular
      interaction and uptake of DNA complexes.
AB  - The cellular uptake of plasmid DNA complexes with a series of tertiary amine
      methacrylate-ethylene glycol (DMAEMA-EG) copolymers with various architectures
      was studied using flow cytofluorometry and laser confocal microscopy. The
      complexes displayed different rates and extents of cellular interaction and
      internalisation, depending on the copolymer molecular architecture. In general,
      introduction of oligo(ethylene glycol) [OEG] or poly(ethylene glycol) [PEG]
      chains decreased both the interaction and cellular internalisation of the DNA
      complexes but subtle differences were observed. Two block copolymers, a 'bottle
      brush' type DMAEMA-block-OEGMA and a linear DMAEMA-block-PEG copolymer (each
      containing a total of 45 EG units), displayed similar uptake profiles. In
      contrast, only relatively low uptake of complexes formed by a comb-type
      statistical copolymer, DMAEMA-stat-PEGMA, was observed, despite each PEG chain
      comprising 45 EG units. Similar trends were observed with three cell lines, A549,
      HepG2 and COS-7. However, the absolute values were cell-dependent, with COS-7
      cells displaying both the highest rate and extent of uptake. Studies of the
      association and uptake of the complexes demonstrated that cell associations
      generally increased over time, with the uptake level and the time profile
      depending on the polymer architecture. Confocal microscopy studies confirmed
      that, with the exception of the poorly transfecting comb-type copolymer, the
      association of complexes with cells resulted in endocytosis.

PMID- 15147813
TI  - PEGylation enhances tumor targeting of plasmid DNA by an artificial cationized
      protein with repeated RGD sequences, Pronectin.
AB  - The objective of this study is to investigate feasibility of a non-viral gene
      carrier with repeated RGD sequences (Pronectin F+) in tumor targeting for gene
      expression. The Pronectin F+ was cationized by introducing spermine (Sm) to the
      hydroxyl groups to allow to polyionically complex with plasmid DNA. The
      cationized Pronectin F+ prepared was additionally modified with poly(ethylene
      glycol) (PEG) molecules which have active ester and methoxy groups at the
      terminal, to form various PEG-introduced cationized Pronectin F+. The cationized
      Pronectin F+ with or without PEGylation at different extents was mixed with a
      plasmid DNA of LacZ to form respective cationized Pronectin F+-plasmid DNA
      complexes. The plasmid DNA was electrophoretically complexed with cationized
      Pronectin F+ and PEG-introduced cationized Pronectin F+, irrespective of the
      PEGylation extent, although the higher N/P ratio of complexes was needed for
      complexation with the latter Pronectin F+. The molecular size and zeta potential
      measurements revealed that the plasmid DNA was reduced in size to about 250 nm
      and the charge was changed to be positive by the complexation with cationized
      Pronectin F+. For the complexation with PEG-introduced cationized Pronectin F+,
      the charge of complex became neutral being almost 0 mV with the increasing
      PEGylation extents, while the molecular size was similar to that of cationized
      Pronectin F+. When cationized Pronectin F+-plasmid DNA complexes with or without
      PEGylation were intravenously injected to mice carrying a subcutaneous Meth-AR-1
      fibrosarcoma mass, the PEG-introduced cationized Pronectin F+-plasmid DNA complex
      specifically enhanced the level of gene expression in the tumor, to a
      significantly high extent compared with the cationized Pronectin F+-plasmid DNA
      complexes and free plasmid DNA. The enhanced level of gene expression depended on
      the percentage of PEG introduced, the N/P ratio, and the plasmid DNA dose. A
      fluorescent microscopic study revealed that the localization of plasmid DNA in
      the tumor tissue was observed only for the PEG-introduced cationized Pronectin F+
      plasmid DNA complex injected. We conclude that the PEGylation of cationized
      Pronectin F+ is a promising way to enable the plasmid DNA to target to the tumor
      for gene expression.

PMID- 15147814
TI  - Enhanced in vitro DNA transfection efficiency by novel folate-linked
      nanoparticles in human prostate cancer and oral cancer.
AB  - Novel folate-linked, cationic nanoparticles (NPs) were developed and evaluated
      for potential use for gene delivery to human oral cancer (KB cells) and human
      prostate cancer (LNCaP cells), which abundantly expressed folate binding
      proteins. Folate-polyethylenglycol-distearoylphosphatidylethanolamine conjugate
      (f-PEG-DSPE) was incorporated in NPs composed of 3([N-(N',N'-dimethylaminoethane)
      carbamoyl] cholesterol (DC-Chol) and Tween 80. NP-0.3FT, -1FT and -1FLT, which
      contain 0.3 and 1 mol% f-PEG2000-DSPE, and 1 mol% f-PEG5000-DSPE, respectively,
      showed about 100-200 nm in size. The NP/plasmid DNA complex (nanoplex) remained
      in an injectable size (230-340 nm) and slightly increased its size in serum. The
      association of NP-1FT with KB cells was enhanced by f-PEG2000-DSPE and was
      blocked by co-incubation with free folic acid in medium. In transfection
      activity, the NP-1FT, but not NP-1FLT, showed high activity into KB and LNCaP
      cells in the presence of serum. The NP-0.3FT also showed high activity into LNCaP
      cells, but not KB cells. In RT-PCR analysis, KB cells strongly expressed folate
      receptors mRNA, but LNCaP cells did not. In contrast, LNCaP cells expressed mRNA
      of prostate-specific membrane antigen (PSMA), which interacts with the folate
      substrate. Uptake mechanism of folate-linked NPs in LNCaP cells may be different
      from that in KB cells. This is the first report that folate-linked NPs
      selectively deliver the DNA to LNCaP cells, suggesting that such NPs are
      potentially targeted vectors to prostate cancer for gene delivery.

PMID- 15147815
TI  - Biomaterial-associated thrombosis: roles of coagulation factors, complement,
      platelets and leukocytes.
AB  - Our failure to produce truly non-thrombogenic materials may reflect a failure to
      fully understand the mechanisms of biomaterial-associated thrombosis. The
      community has focused on minimizing coagulation or minimizing platelet adhesion
      and activation. We have infrequently considered the interactions between the two
      although we are generally familiar with these interactions. However, we have
      rarely considered in the context of biomaterial-associated thrombosis the other
      major players in blood: complement and leukocytes. Biomaterials are known
      agonists of complement and leukocyte activation, but this is frequently studied
      only in the context of inflammation. For us, thrombosis is a special case of
      inflammation. Here we summarize current perspectives on all four of these
      components in thrombosis and with biomaterials and cardiovascular devices. We
      also briefly highlight a few features of biomaterial-associated thrombosis that
      are not often considered in the biomaterials literature: The importance of tissue
      factor and the extrinsic coagulation system. Complement activation as a prelude
      to platelet activation and its role in thrombosis. The role of leukocytes in
      thrombin formation. The differing time scales of these contributions.

PMID- 15147816
TI  - Biocompatibility of beta-stabilizing elements of titanium alloys.
AB  - In comparison to the presently used alpha + beta titanium alloys for biomedical
      applications, beta-titanium alloys have many advantageous mechanical properties,
      such as an improved wear resistance, a high elasticity and an excellent cold and
      hot formability. This will promote their future increased application as
      materials for orthopaedic joint replacements. Not all elements with beta
      stabilizing properties in titanium alloys are suitable for biomaterial
      applications-corrosion and wear processes cause a release of these alloying
      elements to the surrounding tissue. In this investigation, the biocompability of
      alloying elements for beta- and near beta-titanium alloys was tested in order to
      estimate their suitability for biomaterial components. Titanium (grade 2) and the
      implant steel X2CrNiMo18153 (AISI 316 L) were tested as reference materials. The
      investigation included the corrosion properties of the elements, proliferation,
      mitochondrial activity, cell morphology and the size of MC3T3-E1 cells and GM7373
      cells after 7 days incubation in direct contact with polished slices of the
      metals. The statistical significance was considered by Weir-test and Lord-test
      (alpha = 0.05). The biocompatibility range of the investigated metals is
      (decreasing biocompatibility): niobium-tantalum, titanium, zirconium-aluminium
      316 L-molybdenum.

PMID- 15147817
TI  - The characteristics of a hydroxyapatite-chitosan-PMMA bone cement.
AB  - In this study, we propose a new bioactive bone cement (BBC), composed of natural
      bone powder (hydroxyapatite; HA), chitosan powder, and the currently available
      polymethylmethacrylate (PMMA) bone cement, for use in orthopedic surgeries such
      as vertebroplasty or as bone filler. Three types of BBCs (BBC I, BBC II, and BBC
      III) were prepared with different composition ratios. In vitro tests and animal
      studies were performed with the new BBCs, and with a currently available
      commercial PMMA bone cement. Surface morphology, chemical composition, changes in
      pH over time, exothermic temperatures, intrusion, and cellular responses were
      investigated in vitro. Scanning electron microscopy (SEM) and radiological and
      histological examinations were performed in animal studies. The results showed
      that the major components of the BBCs were C, O, Ca, P, Cl, Si, S, Ba, and Mg.
      The pH values of the BBCs decreased after 1 day, but eventually recovered to 7.2
      7.4. The water absorbency, weight loss, and porosity of the BBCs were higher than
      those of pure PMMA, but the compressive Young's modulus and the ultimate
      compressive strength (UCS) of the BBCs were lower than those of pure PMMA. The
      exothermic temperatures of the BBCs were considerably lower than that of pure
      PMMA. BBC II and III required longer times to solidify than did pure PMMA.
      Intrusion tests showed that the BBCs were more intrusive than was pure PMMA. Cell
      proliferation tests demonstrated that BBC II was preferable to pure PMMA for cell
      attachment and proliferation. No cytotoxic characteristics were found associated
      with any of the BBCs. In animal tests, BBC II was more biocompatible and
      osteoconductible than was pure PMMA. The results of in vitro and animal studies
      indicated that the proposed BBCs have potential clinical application as
      replacements for the pure PMMA bone cements currently in use.

PMID- 15147818
TI  - Monitoring the self-assembly of chitosan/glutaraldehyde/cysteamine/Au-colloid and
      the binding of human serum albumin with hesperidin.
AB  - A new method for monitoring, in real-time, the self-assembly of
      chitosan/glutaraldehyde/cysteamine (CGC) on the gold surface and the
      immobilization of Au-colloid on CGC membrane with piezoelectric quartz crystal
      impedance (PQCI) are firstly proposed. Cyclic voltammogram and electrochemical
      impedance spectroscopy were also use to investigate the formation of Au
      colloid/CGC. The viscosity-average molecular weight of chitosan used was firstly
      estimated as 16.8 x 10(5) with piezoelectric quartz crystal (PQC) sensor. On the
      basis of the analysis of the multi-dimensional information provided by PQCI, two
      stages existed in chitosan drying course: the frequency shift of the first stage
      was controlled by viscoelastic of the liquid, while the total frequency shift was
      due to mass change. The cross-link ratio of glutaraldehyde with chitosan was
      about 0.13, while for glutaraldehyde with cysteamine was about 0.217. PQCI also
      showed that the Au-colloid immobilization is a first-order reaction, while the
      HSA immobilization is a sum of two exponential functions, e.g., adsorption and re
      arrangement. The association of the immobilized HSA with the purified hesperidin
      was monitored, and the association constant was estimated as 3.42 ml mg(-1) by
      Scatchard analysis.

PMID- 15147820
TI  - Chondrogenic differentiation of human mesenchymal stem cells using a
      thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer.
AB  - Poly(N-isopropylacrylamide) (PNIPAAm) is known to be thermally responsive
      material and has a lower critical solution temperature (LCST, 32 degrees C) at
      which a macromolecular transition from a hydrophilic to a hydrophobic structure
      occurs. Chitosan is a useful natural polymeric biomaterial due to its
      biocompatibility and biodegradable properties. It has good characteristics for
      cell attachment, proliferation and viability. The aim of this study was to assess
      the ability to differentiate from mesenchymal stem cells (MSCs) to chondrocytes
      and mass formation using a newly developed injectable material, a thermosensitive
      (water-soluble chitosan-g-PNIPAAm) gel, and evaluate cartilage formation in vivo
      after injecting a cell-thermosensitive gel complex. The MSCs were cultured in the
      chitosan-PNIPAAm in vitro. Fluorescence-activated cell sort analysis, viability
      test, collagen type I, II, X formation and the aggrecan levels were examined.
      These cultured cells can be easily recovered from a copolymer gel by simply
      lowering the temperature. An animal study was performed to assess cartilage
      formation in the submucosal layer of the bladder of rabbits. The cartilage
      formation could be detected. This can be used to treat vesicoureteral reflux or
      reflux esophagitis by the effective mass effect. This is a simple method (sol-gel
      technique in LCST), and good cartilage formation occurs in the bladder tissue.

PMID- 15147819
TI  - The effect of scaffold degradation rate on three-dimensional cell growth and
      angiogenesis.
AB  - Even though degradation products of biodegradable polymers are known to be
      largely non-cytotoxic, little detailed information is available regarding the
      degradation rate-dependent acidic byproduct effect of the scaffold. In vitro and
      in vivo scaffold degradation rate could be differentiated using a fast degrading
      polymer (e.g., poly D, L-lactic-glycolic acid co-polymer, PLGA, 50:50) and a slow
      degrading polymer (e.g., poly epsilon-caprolactone, PCL). We applied a new method
      to develop uniform 10 microm thickness of high porous scaffolds using a computer
      controlled knife coater with a motion stage and exploiting phase transition
      properties of a combination of salts and water in salt-leaching method. We then
      verified in vitro the effect of fast degradation by assessing the viability of
      primary mouse aortic smooth muscle cell cultured in the three-dimensional
      scaffolds. We found that cell viability was inversely related to degradation rate
      and was dependent on the depth from the seeding (upper) surface toward the lower
      surface. The pH measurement of culture medium using fluorescence probes showed
      time-dependent decrease in pH in the PLGA scaffolds, corresponding to PLGA
      degradation, and closely related to cell viability. In vivo analysis of scaffolds
      implanted subcutaneously into the back of mice, showed significant differences in
      inflammation and cell invasion into PLGA vs. PCL. Importantly, these were
      correlated with the degree of the functional angiogenesis within the scaffolds.
      Again, PLGA scaffolds demonstrated less cell mobilization and less angiogenesis,
      further supporting the negative effect of the acidic environment created by the
      degradation of biocompatible polymers.

PMID- 15147821
TI  - Functional cardiac cell constructs on cellulose-based scaffolding.
AB  - Cellulose and its derivatives have been successfully employed as biomaterials in
      various applications, including dialysis membranes, diffusion-limiting membranes
      in biosensors, in vitro hollow fibers perfusion systems, surfaces for cell
      expansion, etc. In this study, we tested the potential of cellulose acetate (CA)
      and regenerated cellulose (RC) scaffolds for growing functional cardiac cell
      constructs in culture. Specifically, we demonstrate that CA and RC surfaces are
      promoting cardiac cell growth, enhancing cell connectivity (gap junctions) and
      electrical functionality. Being optically clear and essentially non
      autofluorescent, CA scaffolds did not interfere with functional optical
      measurements in the cell constructs. Molding to follow fine details or complex
      three-dimensional shapes are additional important characteristics for scaffold
      design in tissue engineering. Biodegradability can be controlled by hydrolysis,
      de-acetylization of CA and cytocompatible enzyme (cellulase) action, with glucose
      as a final product. Culturing of cardiac cells and growth of tissue-like cardiac
      constructs in vitro could benefit from the versatility and accessibility of
      cellulose scaffolds, combining good adhesion (comparable to the standard tissue
      culture treated polystyrene), molding capabilities down to the nanoscale
      (comparable to the current favorite in soft lithography-polydimethylsiloxane)
      with controlled biodegradability.

PMID- 15147822
TI  - Poly(D,L lactic-co-glycolic acid) microspheres as biodegradable microcarriers for
      pluripotent stem cells.
AB  - The pluripotent nature and proliferative capacity of embryonic stem cells makes
      them an attractive cell source for tissue engineering and regeneration. In our
      study we investigated the use of poly(D,L-lactic-co-glycolic acid) (PLGA)
      microspheres as biodegradable microcarriers of pluripotent cells and as delivery
      systems of bioactive factors, which influence cell differentiation. The
      pluripotent P19 embryonal carcinoma cell line was used as a model to study cell
      attachment, growth and differentiation of pluripotent stem cells on PLGA
      microspheres. Retinoic acid (RA) was encapsulated in the PLGA microcarriers to
      influence cell differentiation-more specifically, to induce P19 cell
      differentiation into neurons. The results revealed that P19 cells attach and grow
      on the surface of the RA loaded PLGA microspheres. Moreover, the RA loaded PLGA
      microspheres were shown to be as effective as soluble RA at inducing P19 cell
      differentiation into neurons. Hence, the results of these ex vivo studies clearly
      demonstrate the capacity of PLGA microspheres to serve a dual role as both
      delivery systems of bioactive factors and as scaffolds for pluripotent cells.
      More importantly, our study demonstrates the potential use of PLGA microspheres
      as transplantation matrices of pluripotent stem cells for tissue engineering and
      regeneration.

PMID- 15147823
TI  - The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue
      engineered cartilaginous constructs.
AB  - Repair of articular cartilage defects using tissue engineered constructs composed
      of a scaffold and cultured autologous cells holds promise for future treatments.
      However, nutrient limitation (e.g. oxygen) has been suggested as a cause of the
      onset of chondrogenesis solely within the peripheral boundaries of larger
      constructs. In the present study, oxygen gradients were evaluated by
      microelectrode measurements in two porous polyethylene glycol
      terephthalate/polybutylene terephthalate (PEGT/PBT) scaffold architectures, a
      compression-molded and particle-leached sponge (CM) and a 3D-deposited fiber
      (3DF) scaffold. During the first 14 days in vitro, gradients intensified, after
      which a gradual decrease of the gradients was observed in vitro. In vivo,
      however, gradients changed instantly and became less pronounced. Although similar
      gradients were observed regardless of scaffold type, significantly more cells
      were present in the center of 3DF constructs after 2 weeks of in vivo culture.
      Our results stress the importance of a rationally designed scaffold for tissue
      engineering applications. Organized structures, such as the 3DF PEGT/PBT polymer
      scaffolds, offer possibilities for regulation of nutrient supply and, therefore,
      hold promise for clinical approaches for cartilage repair.

PMID- 15147824
TI  - The influence of microscale topography on fibroblast attachment and motility.
AB  - The ability of a cell to attach and migrate on a substrate or scaffold is
      important in the field of tissue engineering and biomaterials, and is thus
      extensively studied. When considering tissue-engineering applications, a highly
      porous scaffold is required to guide cell growth and proliferation in three
      dimensions. However existing scaffolds are less than ideal for actual
      applications, not only as they lack mechanical strength due to pore size and have
      regular distribution, but also they do not ensure cell attachment, in-growth and
      organisation. In this study, microfabrication technology was used to create
      regular arrays of pits on a two-dimensional quartz surface (7, 15 and 25 microm
      diameter, 20 and 40 microm spacing). The patterned surface thus exhibited
      spatially separated mechanical edges akin to the basic structural element of a
      three-dimensional network, and was used as a model system for studying the
      effects of substrate microgeometry on fibroblast attachment and motility. Results
      clearly showed that fibroblast interaction with the pit edges depended on both
      diameter, and therefore angle of circumference, and inter pit spacing, with the
      largest diameter permitting cells to enter the pits. Interestingly, the highest
      cell proliferation rates were recorded on the smaller pits. Such information may
      provide details on possible pore sizes for use in synthetic tissue engineering
      scaffolds that aim to support fibroblast in-growth and subsequent proliferation.

PMID- 15147825
TI  - Effect of resin hydrophilicity and water storage on resin strength.
AB  - This study evaluated the change in the ultimate tensile strength (UTS) of five
      polymerised resin blends of increasing hydrophilicity, after ageing in distilled
      water or silicon oil. Resin blocks were prepared from each resin blend by
      dispensing the uncured resin into a flexible, embedding mould, containing
      multiple cavities. The resins were polymerised in the moulds under nitrogen at
      551.6 kPa and light-activated at 125 degrees C for 10 min. After dry ageing for
      24 h at 37 degrees C, the middle third of each resin specimen was trimmed into an
      'I' shape. Fifteen control specimens were randomly selected from each resin blend
      for baseline UTS evaluation. The UTS of the experimental specimens were
      determined after 1, 3, 6 and 12 months of ageing in water or oil. The UTS of each
      group of resins at different storage periods in water or oil were analysed using
      the Friedman multiple ANOVA on ranks and Dunn's multiple comparison tests at 95%
      confidence level. Significant reduction (p < 0.01) in UTS was observed in Groups
      II-V resins after 12-month storage in water, while the most hydrophobic Group I
      resin showed no significant change (p > 0.05) in the same period. The percentage
      reduction in UTS increased with the hydrophilicity of the resin blends. Long-term
      water storage of hydrophilic resin blends such as those employed in dentine
      adhesives, resulted in a marked reduction in their mechanical strength that may
      compromise the durability of resin-dentine bonds.

PMID- 15147826
TI  - Autonomic neural signals in bone: physiological implications for mandible and
      dental growth.
AB  - Signals derived from the autonomic nervous system exert potent effects on
      osteoclast and osteoblast function. A ubiquitous sympathetic and sensory
      innervation of all periosteal surfaces exists and its disruption affects bone
      remodeling. Several neuropeptides, neurohormones and neurotransmitters and their
      receptors are detectable in bone. Bone mineral content decreased in
      sympathetically denervated mandibular bone. When a mechanical stress was
      superimposed on mandibular bone by cutting out the lower incisors, an increase in
      bone density ensued providing the sympathetic innervation was intact. A lower
      eruption rate of sympathetically denervated incisors at the impeded eruption
      side, and a higher eruption rate of denervated incisors at the unimpeded side
      were also observed. A normal sympathetic neural activity appears to be a pre
      requisite for maintaining a minimal normal unimpeded incisor eruption and for
      keeping the unimpeded eruption to attain abnormally high velocities under
      conditions of stimulated incisor growth. These and other results suggest that the
      sympathetic nervous system plays an important role in mandibular bone metabolism.

PMID- 15147827
TI  - Enhancement of ovalbumin-specific IgA responses via oral boosting with antigen co
      administered with an aqueous Solanum torvum extract.
AB  - An experiment was conducted with the objective to enhance mucosal immunity
      against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from
      the fruit of Solanum torvum (STE). Five groups of female ICR mice aged
      approximately 8 weeks at the commencement of the experiment were caged in groups
      of eight and received various treatments. The treatments included OVA alone, OVA
      with cholera toxin (CT), and OVA with various doses of STE. Mice were primed
      intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg
      CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14
      days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or
      with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs
      obtained for analysis of the immune response. Intestinal, faecal and pulmonary
      OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that
      received booster combinations of OVA/CT and OVA with all extract doses (p<0.05).
      Specific serum IgG titres did not differ significantly between groups. It is
      concluded that STE can significantly enhance secretory immunity in the intestine
      to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable
      to that of CT.

PMID- 15147829
TI  - The involvement of integrin alphavbeta3 in polymorphonuclear leukocyte-induced
      angiogenesis in bovine aortic endothelial cells.
AB  - We have previously reported that angiogenesis stimulated by adhesion of
      polymorphonuclear leukocytes (PMNs) to endothelial cells (ECs) via intercellular
      adhesion molecule-1 (ICAM-1) might be mediated by a transcription factor, ets-1,
      which regulates adhesion molecules such as integrins related to angiogenesis.
      However, the regulation mechanisms of PMN-induced angiogenesis mediated by ICAM-1
      remain unclear. Therefore, we investigated the effects of PMN on EC attachment to
      the extracellular matrix (ECM), which is one of the critical elements for
      angiogenesis development. After the addition of PMNs, attachment of bovine aortic
      endothelial cells (BAECs) to vitronectin, which is known as a ligand for integrin
      alpha(v)beta(3), increased greatly. Stimulation of BAEC with PMN induced
      expressions of integrin beta(3) mRNA and protein. PMN-induced angiogenesis was
      inhibited by Arg-Gly-Asp (RGD) peptide and LM609 anti-alpha(v)beta(3) antibody.
      The PMN-induced BAEC attachment to vitronectin was inhibited by ets-1 antisense
      oligonucleotide and anti-ICAM-1 antibody. These results suggested that
      enhancement of EC attachment to ECM via integrin alpha(v)beta(3) participated in
      the development of PMN-induced angiogenesis. Furthermore, the increase in EC
      attachment to ECM by ligation of PMN to ICAM-1 might be regulated by Ets-1
      expression.

PMID- 15147830
TI  - Negative regulation of the protein kinase C activator-induced ICAM-1 expression
      in the human bronchial epithelial cell line NCI-H292 by p44/42 mitogen-activated
      protein kinase.
AB  - The role of p44/42 mitogen-activated protein kinase (MAPK) in the expression of
      intercellular adhesion molecule-1 (ICAM-1) in NCI-H292 cells, a human bronchial
      epithelial cell line, was analyzed. Treatment with the protein kinase C (PKC)
      activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) or interferon
      gamma (IFN-gamma) (100 U/ml) induced phosphorylation of p44/42 MAPK. The MEK
      inhibitor U0126 (0.1 to 10 microM) enhanced the TPA-induced ICAM-1 expression but
      not the IFN-gamma-induced one. U0126 also enhanced the ICAM-1 expression induced
      by two other PKC activators teleocidin (22.5 nM) and aplysiatoxin (14.9 nM).
      Furthermore, PD98059 (0.5 to 50 microM), another MEK inhibitor, enhanced the TPA
      induced ICAM-1 expression as well. The inhibitor of p38 MAPK SB203580 did not
      affect the TPA-induced ICAM-1 expression. BAY11-7082, an inhibitor of nuclear
      factor kappaB (NF-kappaB) activation, and MG132, a 26S proteasome inhibitor,
      reduced the TPA-induced ICAM-1 expression but not the IFN-gamma-induced one. TPA
      partially decreased the level of IkappaB-alpha and the reduction was further
      augmented by U0126 in a concentration-dependent manner. These findings suggested
      that, in NCI-H292 cells, p44/42 MAPK suppresses PKC activator-induced NF-kappaB
      activation, thus negatively regulating the PKC activator-induced ICAM-1
      expression but not the IFN-gamma-induced one.

PMID- 15147828
TI  - Diverse effects of long-term treatment with imidapril and irbesartan on cell
      growth signal, apoptosis and collagen type I expression in the left ventricle of
      spontaneously hypertensive rats.
AB  - To compare diverse effects of angiotensin II type 1 receptor antagonists
      (irbesartan) and angiotensin converting enzyme inhibitors (imidapril) on left
      ventricular remodeling in spontaneously hypertensive rats (SHR). Thirty male SHR
      were randomly divided into three groups: SHR-IR (treated with irbesartan, 50
      mg/kg), SHR-IM (imidapril, 3 mg/kg), SHR-C (placebo). Ten male Wistar Kyoto rats
      (WKY) treated with placebo acted as the control. All treatments were administered
      once daily from 14 to 27 weeks of age. Imidapril and irbesartan have the similar
      inhibitor effects on blood pressure and left ventricular mass indexes in SHR.
      Despite both drugs suppressed ERK-1 protein expression, decreased cardiomyocytes
      apoptosis index, blocked collagen type I deposition, reduced TGF-beta(1) gene
      expression in SHR, imidapril elicits a stronger inhibitory effect. Irbesartan had
      little effect on MKP-1 protein expression, but imidapril decreased it
      significantly. As a result, the ERK-1/MKP-1 ratio in SHR-IR was significantly
      greater than that in SHR-IM (P < 0.05). These results suggest that the balance
      between MKP-1 and ERKs in myocardial tissue is important for cardiac cell
      proliferation and growth. They also indicate that the similar efficacy of
      antihypertensive treatment in reducing blood pressure does not predict the
      similar capacity to control the individual facet of left ventricular remodeling.
      Irbesartan is more effective in regressing the homeostasis between ERK-1 and MKP
      1, however imidapril is superior in suppressing apoptosis and collagen synthesis
      in cardiac tissue.

PMID- 15147831
TI  - Characteristics of selenazolidine prodrugs of selenocysteine: toxicity, selenium
      levels, and glutathione peroxidase induction in A/J mice.
AB  - We have previously reported the synthesis and characterization of two new classes
      of selenazolidine-4(R)-carboxylic acids (2-oxo and 2-methyl-SCAs) (OSCA and MSCA,
      respectively), as well as the "parent" compound, selenazolidine-4(R)-carboxylic
      acid (SCA, selenaproline). These compounds were designed as prodrugs of L
      selenocysteine with potential application in cancer chemoprevention or other
      clinical uses. We will be exploring the chemopreventive activity of the new
      compounds in the well-established A/J mouse model of tobacco-induced lung
      carcinogenesis. The objectives of the present study were to investigate several
      fundamental biochemical endpoints after selenazolidine administration compared
      with other selenium-containing agents. Groups of mice were fed either AIN-76A
      diet alone or the diet supplemented with the following selenium compounds (ppm
      Se): sodium selenite (5), L-selenomethionine (3.75), L-selenocystine (15), Se
      methyl-L-selenocysteine (3), MSCA (5, 10, or 15), OSCA (5, 10, or 15), or SCA (5,
      10, or 15). After 28 days of supplementation, toxicity of the selenazolidines was
      not evident, as measured by outward appearance and behavior, body and organ
      weight changes, and histological evaluation of liver and lung tissue. Select
      treatment groups showed significant increases in selenium levels in blood and
      tissues. Increased activity of selenium-dependent glutathione peroxidase (GPx) in
      blood and liver illustrated that the selenazolidines provided a source of
      biologically-available selenium.

PMID- 15147832
TI  - Exogenously administered and endogenously produced melatonin reduce hyperbaric
      oxygen-induced oxidative stress in rat lung.
AB  - Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A
      known side effect of HBO is the production of reactive oxygen species. Many
      antioxidants such as vitamins C and E, riboflavin and selenium have been used
      successfully to scavenge the reactive oxygen species caused by HBO
      administration. In this study, we aimed to see if melatonin, a newly discovered
      antioxidant, has a protective effect against the overproduction of reactive
      oxygen species produced by HBO in rat lung tissue. Sixty male Sprague-Dawley rats
      were divided into 5 groups as follows: control, daytime HBO (3 ATA, 120 min),
      daytime HBO plus melatonin (10 mg/kg), nighttime HBO and nighttime HBO (under
      light exposure). The MDA, SOD and CAT levels of daytime and nighttime HBO (under
      light exposure) increased significantly. This significance was not found in the
      daytime HBO plus melatonin and nighttime HBO groups when compared with the
      control. In this study, HBO caused oxidant stress, and melatonin decreased the
      levels of MDA, SOD and CAT. Moreover, endogenous melatonin was found to be a more
      effective antioxidant than exogenous 10 mg/kg melatonin.

PMID- 15147834
TI  - Gallium arsenide exposure impairs processing of particulate antigen by
      macrophages: modification of the antigen reverses the functional defect.
AB  - Gallium arsenide (GaAs), a semiconductor used in the electronics industry, causes
      systemic immunosuppression in animals. The chemical's impact on macrophages to
      process the particulate antigen, sheep red blood cells (SRBC), for a T cell
      response in culture was examined after in vivo exposure of mice. GaAs-exposed
      splenic macrophages were defective in activating SRBC-primed lymph node T cells
      that could not be attributed to impaired phagocytosis. Modified forms of SRBC
      were generated to examine the compromised function of GaAs-exposed macrophages.
      SRBC were fixed to maintain their particulate nature and subsequently delipidated
      with detergent. Delipidation of intact SRBC was insufficient to restore normal
      antigen processing in GaAs-exposed macrophages. However, chemically exposed cells
      efficiently processed soluble sheep proteins. These findings suggest that the
      problem may lie in the release of sequestered sheep protein antigens, which then
      could be effectively cleaved to peptides. Furthermore, opsonization of SRBC with
      IgG compensated for the macrophage processing defect. The influence of signal
      transduction and phagocytosis via Fcgamma receptors on improved antigen
      processing could be dissociated. Immobilized anti-Fcgamma receptor antibody
      activated macrophages to secrete a chemokine, but did not enhance processing of
      unmodified SRBC by GaAs-exposed macrophages. Restoration of normal processing of
      particulate SRBC by chemically exposed macrophages involved phagocytosis through
      Fcgamma receptors. Hence, initial immune responses may be very sensitive to GaAs
      exposure, and the chemical's immunosuppression may be averted by opsonized
      particulate antigens.

PMID- 15147833
TI  - Lack of sexual dimorphism in alcohol-induced liver damage (ALD) in rats treated
      chronically with ethanol-containing low carbohydrate diets: The role of ethanol
      metabolism and endotoxin.
AB  - Evidence has been presented suggesting that females are significantly more
      susceptible to alcohol-induced liver damage (ALD) than males. In the current
      study, we examined sexual dimorphism in hepatic pathology, metabolism and
      cytokine profiles using two different rat models of ALD. Male and female Sprague
      Dawley or Wistar rats were fed ethanol-containing low-carbohydrate liquid diets
      using oral or intragastric methods for 42 or 60 days. In both models, ethanol
      treatment produced similar significant liver hyperplasia accompanied by increases
      in plasma ALT, steatosis, inflammation and necrosis (p < 0.05). Greater pathology
      scores were observed in the intragastrically infused rats. Males did not differ
      significantly from females in serum ALT values or pathology despite greater
      elevations in TNFalpha and IL-1beta mRNAs in ethanol-treated female rat livers (p
      < 0.05). Furthermore, there was no sexual dimorphism in blood ethanol
      concentrations or CYP2E1-induction even though sexually dimorphic alterations in
      other hepatic cytochrome P450 enzymes were observed. These data do not support
      previous observations that female rats have a greater susceptibility to ethanol
      induced hepatotoxicity than males.

PMID- 15147835
TI  - Evidence for genistein mediated cytotoxicity and apoptosis in rat brain.
AB  - The effects of chronic treatment with high doses of genistein, a major isoflavone
      of soybeans and soy-based products, have yet to be determined and what is known
      remains controversial. The present study was undertaken to investigate the
      cytotoxic effects of chronic ingestion of genistein on rat brain in vivo and the
      observations were compared with results from in vitro studies with primary
      cultures of cortical neurons. Sprague-Dawley rats were given 2 or 20 mg/day
      genistein (p.o.) for four weeks. The high dose of genistein (20 mg/day)
      significantly increased lactate dehydrogenase (LDH) in rat brain tissue
      homogenates, whereas the low dose of genistein (2 mg/day) decreased LDH. In
      addition, DNA fragmentation was detected in homogenates of brain tissue from rats
      receiving either dose of genistein. These results are consistent with those of in
      vitro studies indicating that high concentrations of genistein caused
      cytotoxicity and DNA ladder formation in primary cultures of cortical neurons.
      Genistein decreased the expression of the 32 kDa caspase-3 precursor and
      increased the levels of cleaved caspase-3 (18 kDa) in both rat brain tissue
      homogenates and in primary cultures of cortical neurons. Furthermore, expression
      of poly (ADP-ribose) polymerase (PARP) was also decreased in both experimental
      systems. These results suggest that chronic administration of genistein at high
      doses may induce cytotoxicity and apoptosis in the rat brain.

PMID- 15147836
TI  - Neuregulin-1 induces expression of Egr-1 and activates acetylcholine receptor
      transcription through an Egr-1-binding site.
AB  - Localization of acetylcholine receptors (AChRs) to neuromuscular synapses is
      mediated, in part, through selective transcription of AChR genes in myofiber
      synaptic nuclei. Neuregulin-1 (NRG-1) and its receptors, ErbBs, are concentrated
      at synaptic sites, and NRG-1 activates AChR synthesis in cultured muscle cells,
      suggesting that NRG-1-ErbB signaling functions to activate synapse-specific
      transcription. Previous studies have demonstrated that NRG-1-induced
      transcription is conferred by cis-acting elements located within 100 bp of 5'
      flanking DNA from the AChR epsilon subunit gene, and that it requires a GABP
      binding site within this region. To determine whether additional regulatory
      elements have a role in NRG-1 responsiveness, we used transcriptional reporter
      assays in a muscle cell line, and we identified an element that is required for
      NRG-1-induced transcription (neuregulin response element, NRE). Proteins from
      myotube extracts bind the NRE and NRG-1 treatment of the cells stimulates this
      binding. The ability of NRG-1 to stimulate formation of a protein-DNA complex
      with the NRE requires induction of protein expression. The complex contains early
      growth response-1 (Egr-1), a member of the Egr family of transcription factors,
      because proteins in the complex bind specifically to an Egr consensus site, and
      formation of the complex is inhibited by antibodies to Egr-1. NRG-1 induces
      expression of Egr-1 in myotubes, which presumably is responsible for the ability
      of NRG-1 to stimulate protein binding to the NRE. These results suggest that NRG
      1 signaling in myotubes involves induction of Egr-1 expression, which in turn
      serves to activate transcription of the AChR epsilon subunit gene.

PMID- 15147837
TI  - Identification of a new antizyme mRNA +1 frameshifting stimulatory pseudoknot in
      a subset of diverse invertebrates and its apparent absence in intermediate
      species.
AB  - The expression of eukaryotic antizyme genes requires +1 translational
      frameshifting. The frameshift in decoding most vertebrate antizyme mRNAs is
      stimulated by an RNA pseudoknot 3' of the frameshift site. Although the
      frameshifting event itself is conserved in a wide variety of organisms from yeast
      to mammals, until recently no corresponding 3' RNA pseudoknot was known in
      invertebrate antizyme mRNAs. A pseudoknot, different in structure and origin from
      its vertebrate counterparts, is now shown to be encoded by the antizyme genes of
      distantly related invertebrates. Identification of the 3' frameshifting
      stimulator in intermediate species or other invertebrates remains unresolved.

PMID- 15147838
TI  - The DNA binding protein H-NS binds to and alters the stability of RNA in vitro
      and in vivo.
AB  - H-NS is an abundant prokaryotic transcription factor that preferentially binds to
      intrinsically bent DNA. Although H-NS has been shown to reduce the transcription
      of over 100 genes, evidence suggests that H-NS can also affect the translation of
      some genes. One such gene, rpoS, specifies a sigma factor, RpoS. The ability of H
      NS to bind to the rpoS mRNA and the non-coding RNA regulator, DsrA, was tested.
      Electrophoretic mobility-shift assays yielded an apparent binding affinity of H
      NS binding to curved DNA of approximately 1 microM, whereas binding to rpoS mRNA
      or DsrA RNA was approximately 3 microM. This RNA binding was not prevented by an
      excess of competitor yeast RNA, suggesting that H-NS specifically bound these
      RNAs. Footprint analysis with a single strand-specific ribonuclease was used to
      identify the H-NS binding site(s) on DsrA and rpoS mRNA. Surprisingly, H-NS
      appeared to enhance the cleavage of DsrA and rpoS mRNA. The enhanced cleavage was
      at sites that were predicted to be single-stranded and did not result from
      contaminating nucleases in the H-NS protein preparation or non-specific effects
      of the nuclease. Quantitative RT-PCR of RNA isolated from wild-type and hns-
      strains revealed that H-NS also affects the stability of DsrA in vivo. Thus H-NS
      appears to modulate RNA stability in vivo and in vitro.

PMID- 15147839
TI  - Investigating the accessibility of the closed domain conformation of citrate
      synthase using essential dynamics sampling.
AB  - A molecular dynamics study of pig heart citrate synthase is presented that aims
      to directly address the question of whether, for this enzyme, the ligand-induced
      closed domain conformation is accessible to the open unliganded enzyme. The
      approach utilises the technique of essential dynamics sampling, which is used in
      two modes. In exploring mode, the enzyme is encouraged to explore domain
      conformations it might not normally sample in free molecular dynamics simulation.
      In targeting mode, the enzyme is encouraged to adopt the domain conformation of a
      target structure. Using both modes extensively, it has been found that when the
      enzyme is prepared from a crystallographic open-domain structure and is in the
      unliganded state, it is unable to adopt the crystallographic closed-domain
      conformation of the liganded enzyme. Likewise, when the enzyme is prepared from
      the crystallographic closed liganded conformation with the ligands removed, it is
      unable to adopt the crystallographic open domain conformation. Structural
      investigations point to a common structural difference that is the source of this
      energy barrier; namely, the shift of alpha-helix 328-341 along its own axis
      relative to the large domain. Without this shift, the domains are unable to close
      or open fully. The charged substrate, oxaloacetate, binds near the base of this
      helix in the large domain and the interaction of Arg329 at the base of the helix
      with oxaloacetate is one that is consistent with the shift of this helix in going
      from the crystallographic open to closed structure. Therefore, the results
      suggest that without the substrate the enzyme remains in a partially open
      conformation ready to receive the substrate. In this way, the efficiency of the
      enzyme should be increased over one that is closed part of the time, with its
      binding site inaccessible to the substrate.

PMID- 15147840
TI  - How thioredoxin can reduce a buried disulphide bond.
AB  - We present a study of the interaction between thioredoxin and the model enzyme
      pI258 arsenate reductase (ArsC) from Staphylococcus aureus. ArsC catalyses the
      reduction of arsenate to arsenite. Three redox active cysteine residues (Cys10,
      Cys82 and Cys89) are involved. After a single catalytic arsenate reduction event,
      oxidized ArsC exposes a disulphide bridge between Cys82 and Cys89 on a looped-out
      redox helix. Thioredoxin converts oxidized ArsC back towards its initial reduced
      state. In the absence of a reducing environment, the active-site P-loop of ArsC
      is blocked by the formation of a second disulphide bridge (Cys10-Cys15). While
      fully reduced ArsC can be recovered by exposing this double oxidized ArsC to
      thioredoxin, the P-loop disulphide bridge is itself inaccessible to thioredoxin.
      To reduce this buried Cys10-Cys15 disulphide-bridge in double oxidized ArsC, an
      intra-molecular Cys10-Cys82 disulphide switch connects the thioredoxin mediated
      inter-protein thiol-disulphide transfer to the buried disulphide. In the initial
      step of the reduction mechanism, thioredoxin appears to be selective for oxidized
      ArsC that requires the redox helix to be looped out for its interaction. The
      formation of a buried disulphide bridge in the active-site might function as
      protection against irreversible oxidation of the nucleophilic cysteine, a
      characteristic that has also been observed in the structurally similar low
      molecular weight tyrosine phosphatase.

PMID- 15147841
TI  - Surface-decoration of microtubules by human tau.
AB  - Tau is a neuronal, microtubule-associated protein that stabilizes microtubules
      and promotes neurite outgrowth. Tau is largely unfolded in solution and
      presumably forms mostly random coil. Because of its hydrophilic nature and
      flexible structure, tau complexed to microtubules is largely invisible by
      standard electron microscopy methods. We applied a combination of high-resolution
      metal-shadowing and cryo-electron microscopy to study the interactions between
      tau and microtubules. We used recombinant tau variants with different domain
      compositions, (1) full length tau, (2) the repeat domain that mediates
      microtubule binding (K19), and (3) two GFP-tau fusion proteins that contain a
      globular marker (GFP) attached to full-length tau at either end. All of these
      constructs bind exclusively to the outside of microtubules. Most of the tau
      related mass appears randomly distributed, creating a "halo" of low-density mass
      spread across the microtubule surface. Only a small fraction of tau creates a
      periodic signal at an 8 nm interval, centered on alpha-tubulin subunits. Our data
      suggest that tau retains most of its disordered structure even when bound to the
      microtubule surface. Hence, it binds along, as well as across protofilaments.
      Nevertheless, even minute concentrations of tau have a strong stabilizing effect
      and effectively scavenge unpolymerized tubulin.

PMID- 15147842
TI  - The folding transition state of the cold shock protein is strongly polarized.
AB  - The cold shock protein CspB from Bacillus subtilis consists of a three-stranded
      (beta1-beta3) and a two stranded (beta4-beta5) sheet, which form a closed beta
      barrel structure. CspB folds and unfolds rapidly in a two-state reaction, and the
      unfolded and the folded molecules interconvert with a time constant of 30 ms at
      the midpoint of the urea-induced transition (at 25 degrees C). The transition
      state of folding is native-like, as judged by the Tanford betaT value of > or
      =0.9. By using a mutational approach and Phi value analysis, we find that the
      folding transition state of CspB is energetically polarized. Despite the high
      betaT value, most Phi values are low. Values close to 1 were found for only a few
      residues, particularly in strand beta1 (Lys5, Val6, Lys7, Asn10). The
      interactions of the Asn10 side-chain with the backbone at positions 12 and 13
      define the turn that connects the strands beta1 and beta2. Lys5 and Val6 in beta1
      interact with residues in beta4, and their high Phi values indicate that an
      energetic linkage between beta1 and beta4 and thus between the two sheets exists
      already in the transition state. We compared our experimental Phi values with
      theoretical predictions of the folding pathway of cold shock proteins. Several of
      them suggest that the entire first sheet is formed in the transition state, and
      some identify the beta1-beta4 pairing as a crucial step in folding. Alternative
      paths that involve formation of the second sheet and beta3-beta5 pairing
      reactions were, however, suggested as well. The calculations gave coarse-grained
      pictures that are limited in resolution to the two sheets of CspB or to the
      elements of secondary structure. They did not identify the key residues with the
      high Phi values within these structural elements.

PMID- 15147843
TI  - The influence of a transmembrane pH gradient on protonation probabilities of
      bacteriorhodopsin: the structural basis of the back-pressure effect.
AB  - Bacteriorhodopsin pumps protons across a membrane using the energy of light. The
      proton pumping is inhibited when the transmembrane proton gradient that the
      protein generates becomes larger than four pH units. This phenomenon is known as
      the back-pressure effect. Here, we investigate the structural basis of this
      effect by predicting the influence of a transmembrane pH gradient on the
      titration behavior of bacteriorhodopsin. For this purpose we introduce a method
      that accounts for a pH gradient in protonation probability calculations. The
      method considers that in a transmembrane protein, which is exposed to two
      different aqueous phases, each titratable residue is accessible for protons from
      one side of the membrane depending on its hydrogen-bond pattern. This method is
      applied to several ground-state structures of bacteriorhodopsin, which residues
      already present complicated titration behaviors in the absence of a proton
      gradient. Our calculations show that a pH gradient across the membrane influences
      in a non-trivial manner the protonation probabilities of six titratable residues
      which are known to participate in the proton transfer: D85, D96, D115, E194,
      E204, and the Schiff base. The residues connected to one side of the membrane are
      influenced by the pH on the other side because of their long-range electrostatic
      interactions within the protein. In particular, D115 senses the pH at the
      cytoplasmic side of the membrane and transmits this information to D85 and the
      Schiff base. We propose that the strong electrostatic interactions found between
      D85, D115, and the Schiff base as well as the interplay of their respective
      protonation states under the influence of a transmembrane pH gradient are
      responsible for the back-pressure effect on bacteriorhodopsin.

PMID- 15147844
TI  - A hidden markov model derived structural alphabet for proteins.
AB  - Understanding and predicting protein structures depends on the complexity and the
      accuracy of the models used to represent them. We have set up a hidden Markov
      model that discretizes protein backbone conformation as series of overlapping
      fragments (states) of four residues length. This approach learns simultaneously
      the geometry of the states and their connections. We obtain, using a statistical
      criterion, an optimal systematic decomposition of the conformational variability
      of the protein peptidic chain in 27 states with strong connection logic. This
      result is stable over different protein sets. Our model fits well the previous
      knowledge related to protein architecture organisation and seems able to grab
      some subtle details of protein organisation, such as helix sub-level organisation
      schemes. Taking into account the dependence between the states results in a
      description of local protein structure of low complexity. On an average, the
      model makes use of only 8.3 states among 27 to describe each position of a
      protein structure. Although we use short fragments, the learning process on
      entire protein conformations captures the logic of the assembly on a larger
      scale. Using such a model, the structure of proteins can be reconstructed with an
      average accuracy close to 1.1A root-mean-square deviation and for a complexity of
      only 3. Finally, we also observe that sequence specificity increases with the
      number of states of the structural alphabet. Such models can constitute a very
      relevant approach to the analysis of protein architecture in particular for
      protein structure prediction.

PMID- 15147845
TI  - Recognition of functional sites in protein structures.
AB  - Recognition of regions on the surface of one protein, that are similar to a
      binding site of another is crucial for the prediction of molecular interactions
      and for functional classifications. We first describe a novel method, SiteEngine,
      that assumes no sequence or fold similarities and is able to recognize proteins
      that have similar binding sites and may perform similar functions. We achieve
      high efficiency and speed by introducing a low-resolution surface representation
      via chemically important surface points, by hashing triangles of physico-chemical
      properties and by application of hierarchical scoring schemes for a thorough
      exploration of global and local similarities. We proceed to rigorously apply this
      method to functional site recognition in three possible ways: first, we search a
      given functional site on a large set of complete protein structures. Second, a
      potential functional site on a protein of interest is compared with known binding
      sites, to recognize similar features. Third, a complete protein structure is
      searched for the presence of an a priori unknown functional site, similar to
      known sites. Our method is robust and efficient enough to allow computationally
      demanding applications such as the first and the third. From the biological
      standpoint, the first application may identify secondary binding sites of drugs
      that may lead to side-effects. The third application finds new potential sites on
      the protein that may provide targets for drug design. Each of the three
      applications may aid in assigning a function and in classification of binding
      patterns. We highlight the advantages and disadvantages of each type of search,
      provide examples of large-scale searches of the entire Protein Data Base and make
      functional predictions.

PMID- 15147846
TI  - Catalysis of proline-directed protein phosphorylation by peptidyl-prolyl
      cis/trans isomerases.
AB  - Proline-directed protein phosphorylation was shown to depend on the capacity of
      the targeted Ser(Thr)-Pro bond to exhibit conformational polymorphism. The
      cis/trans isomer specificity underlying ERK2-catalyzed phosphate transfer leads
      to a complete discrimination of the cis Ser(Thr)-Pro conformer of oligopeptide
      substrates. We investigated in vitro the ERK2-catalyzed phosphorylation of
      Aspergillus oryzae RNase T1 containing two Ser-Pro bonds both of which share high
      stabilization energy in their respective native state conformation, the cis Ser54
      Pro and the trans Ser72-Pro moiety. Despite trans isomer specificity of ERK2, a
      doubly phosphorylated RNase T1 was found as the final reaction product.
      Similarly, the RNase T1 S54G/P55N and RNase T1 P73V variants, which retain the
      prolyl bond conformations of the RNase T1-wt, were both monophosphorylated with a
      catalytic efficiency kcat/KM of 425 M(-1) s(-1) and 1228 M(-1) s(-1),
      respectively. However, initial phosphorylation rates did not depend linearly on
      the ERK2 concentration. The phosphorylation rate of the resulting plateau region
      at high ERK2 concentrations can be increased up to threefold for the RNase T1
      P73V variant in the presence of the peptidyl-prolyl cis/trans isomerase
      Cyclophilin 18, indicating a conformational interconversion as the rate limiting
      step in the catalyzed phosphate group transfer. Using peptidyl-prolyl cis/trans
      isomerases with different substrate specificity, we identified a native state
      conformational equilibrium of the Ser54-Pro bond with the minor trans Ser54-Pro
      bond as the phosphorylation-sensitive moiety. This technique can therefore be
      used for a determination of the ratio and the interconversion rates of prolyl
      bond isomers in the native state of proteins.

PMID- 15147847
TI  - Toward consistent assignment of structural domains in proteins.
AB  - The assignment of protein domains from three-dimensional structure is critically
      important in understanding protein evolution and function, yet little quality
      assurance has been performed. Here, the differences in the assignment of
      structural domains are evaluated using six common assignment methods. Three human
      expert methods (AUTHORS (authors' annotation), CATH and SCOP) and three fully
      automated methods (DALI, DomainParser and PDP) are investigated by analysis of
      individual methods against the author's assignment as well as analysis based on
      the consensus among groups of methods (only expert, only automatic, combined).
      The results demonstrate that caution is recommended in using current domain
      assignments, and indicates where additional work is needed. Specifically, the
      major factors responsible for conflicting domain assignments between methods,
      both experts and automatic, are: (1) the definition of very small domains; (2)
      splitting secondary structures between domains; (3) the size and number of
      discontinuous domains; (4) closely packed or convoluted domain-domain interfaces;
      (5) structures with large and complex architectures; and (6) the level of
      significance placed upon structural, functional and evolutionary concepts in
      considering structural domain definitions. A web-based resource that focuses on
      the results of benchmarking and the analysis of domain assignments is available
      at

PMID- 15147848
TI  - Highlighting the role of technologies in the battle against maternal mortality:
      introduction to a Bellagio workshop.

PMID- 15147849
TI  - Achieving appropriate design and widespread use of health care technologies in
      the developing world. Overcoming obstacles that impede the adaptation and
      diffusion of priority technologies for primary health care.
AB  - OBJECTIVES: To identify and describe constraints facing the development and
      dissemination of technologies appropriate for public health care challenges and
      solutions in the developing world. METHODS: Review of lessons learned in
      development and introduction of numerous health technologies as experienced by a
      non-profit organization working on technologies for 25 years. RESULTS: Many
      obstacles prevent appropriate technologies from reaching widespread use and
      acceptance. These include low profit margins in developing world markets,
      regulatory constraints, and the need for systems changes. Strong public/private
      sector partnerships and realistic approaches to working in these environments
      make a difference. CONCLUSIONS: There is a growing awareness of the need for new
      technologies and experience with strategies that can make them happen. Some
      technologies with documented value for maternal care in developing world settings
      appear to be stuck short of widespread acceptance and use. Understanding the
      factors impeding their progress can enable the public sector and its
      collaborators to organize and facilitate their progress more effectively.

PMID- 15147850
TI  - Auxiliary technologies related to transport and communication for obstetric
      emergencies.
AB  - OBJECTIVES: To review the evidence on appropriate transport and communications
      technologies for obstetrical referrals in developing countries. METHODS: Review
      of articles published in peer-reviewed journals and gray literature, supplemented
      by email and telephone consultations with key informants and field programmers.
      RESULTS: A wide range of transportation options have been attempted. Initial
      approaches--such as those relying on ambulances owned and operated by health
      systems--have evolved into recommendations that emphasize community-based
      solutions. There are fewer options within the realm of communications
      technologies, and the recommendations are more consistent. Public health
      researchers are only beginning to evaluate the cost and effectiveness of
      different options. CONCLUSIONS: One of the greatest barriers to effective use of
      transport and communications for obstetric emergencies is the short time interval
      necessary for action, which limits options for obstetric referrals more than for
      other medical referrals. Although evidence is still scarce, experience suggests
      that motorized transport is likely to be the most acceptable and effective
      transportation option. More sophisticated communications technologies such as
      cell phones are both practical and effective, and are increasingly becoming the
      technologies of choice for low-resource settings.

PMID- 15147851
TI  - Vitamin A deficiency as a preventable cause of maternal mortality in
      undernourished societies: plausibility and next steps.
AB  - Maternal vitamin A deficiency is a public health problem in the developing world.
      Recent evidence from Nepal suggests that supplementing populations of rural,
      poor, and undernourished women with a recommended dietary amount of vitamin A--or
      its equivalent as beta-carotene--can lower mortality risk related to pregnancy
      and childbirth, presumably by reducing the severity of conditions such as sepsis,
      tuberculosis, and diarrheal diseases. An adequate intake of beta-carotene may
      also reduce some maternal health risks related to oxidative stress. These
      findings reveal the potential for vitamin A and other micronutrient interventions
      to improve maternal and infant health and survival. They also present important
      implementation challenges for the developing world.

PMID- 15147853
TI  - Postpartum hemorrhage in developing countries: is the public health community
      using the right tools?
AB  - OBJECTIVES: To identify new and underutilized technologies that may assist in
      reducing maternal mortality due to obstetric hemorrhage. METHODS: Review of
      published and unpublished literature, including systematic reviews of randomized
      trials and individual clinical studies. RESULTS: Hemorrhage, primarily
      postpartum, accounts for approximately 25% of maternal deaths globally.
      Uterotonic drugs offer great promise for both prevention and management of
      postpartum hemorrhage (PPH). Other technologies--such as anti-shock garments,
      umbilical vein injection of oxytocin, and simple anemia detection methods-
      represent potential new opportunities to reduce PPH-related mortality.
      CONCLUSIONS: Clinical and operational research is needed to answer remaining
      questions about misoprostol, the anti-shock garment, and umbilical vein injection
      of oxytocin for retained placenta. Efforts are needed to ensure the availability
      of technologies with proven value, such as oxytocin in Uniject prefilled
      injection devices. Equally important, technologies and techniques with proven
      efficacy--such as active management of third-stage labor and aortic compression-
      must be translated into general use by disseminating the evidence for them,
      incorporating them into national guidelines and training curricula, and ensuring
      the availability of supportive supplies and equipment.

PMID- 15147852
TI  - Methodological and technical issues related to the diagnosis, screening,
      prevention, and treatment of pre-eclampsia and eclampsia.
AB  - In contrast with advances made in treating or eliminating many other serious
      disorders, severe morbidity and mortality associated with pre-eclampsia/eclampsia
      remain among the leading problems that threaten safe motherhood, particularly in
      developing countries. This article reviews technical issues related to diagnosis,
      screening, prevention, and treatment of pre-eclampsia and identifies
      corresponding needs. The authors stress the lack of standardized definitions of
      pre-eclampsia and eclampsia and discuss problems in blood-pressure measurements
      and assessment of urinary protein. They summarize the evidence for prevention
      strategies and screening tests for early detection. For treatment, magnesium
      sulfate has been proven effective, but not widely used. The authors outline
      priorities for narrowing the identified gaps and emphasize the need for
      coordinated efforts to reduce the morbidity and mortality due to pre
      eclampsia/eclampsia. They conclude that the mystery of this disease must be
      resolved to achieve primary prevention of it.

PMID- 15147854
TI  - Puerperal sepsis and maternal mortality: what role can new technologies play?
AB  - OBJECTIVE: To identify new and underutilized technologies to reduce maternal
      mortality related to puerperal sepsis in developing countries. METHOD: Review of
      current medical literature. RESULT: The literature indicates that infection
      control protocols and evidence-based procedures--including prophylactic
      antibiotics for cesarean section or preterm rupture of membranes, and updated
      antibiotic regimens--should be widely adopted. Devices such as hand rubs, needle
      disposal systems, and rapid microbiological diagnostic tests can improve
      compliance and efficiency. Operational research on promising developments like
      vaginal cleansing with antiseptics, vitamin A supplementation, and prophylactic
      antibiotics in high-risk women is needed. CONCLUSION: Sepsis management continues
      to depend on good implementation of established technologies. Program-based
      approaches are required to improve uptake.

PMID- 15147855
TI  - Obstructed labor: using better technologies to reduce mortality.
AB  - OBJECTIVE: To identify, from the best available evidence, underutilized and
      promising technologies that may reduce maternal mortality from obstructed labor.
      METHODS: The author sought systematic reviews of randomized trials, individual
      randomized trials, and, in the absence of randomized data, non-randomized studies
      and clinical consensus. Data were presented according to the level of the
      evidence. RESULTS: Obstructed labor causes approximately 8% of maternal deaths,
      and indirectly contributes to a greater percentage. Proven or widely accepted
      technologies that help reduce mortality from obstructed labor include
      contraception, external cephalic version, the partogram, augmentation of labor,
      selective amniotomy, selective episiotomy, vacuum extraction, caesarean section,
      symphysiotomy, and destructive procedures for non-viable fetuses. Technologies of
      uncertain usefulness include maternal height and shoe size, vaginal cleansing,
      upright posture for delivery and vaginal lubrication. Unuseful technologies
      include pelvimetry, estimating fetal weight, early labor induction, routine
      amniotomy and augmentation, routine episiotomy, and starvation during labor.
      CONCLUSION: Access to well-established technologies, particularly safe caesarean
      section, can reduce maternal mortality in resource-poor countries.

PMID- 15147856
TI  - Improving technologies to reduce abortion-related morbidity and mortality.
AB  - This article reviews the technologies used to diagnose pregnancy and manage
      abortion in developing countries. The author discusses methods of diagnosing
      pregnancy--including physical examination, laboratory and home testing, and
      ultrasound--as well as methods for performing safe abortions. Due to manual
      vacuum aspiration (MVA) advances, vacuum aspiration has become safer and more
      feasible in low-resource settings. The discussion of medical abortion includes
      the advantages and limitations of mifepristone, misoprostol-only regimens,
      methotrexate, and other methods. The author stresses the importance of post
      abortion care and post-abortion contraception and, in the conclusion, identifies
      six areas in which technology can reduce abortion-related morbidity and
      mortality: pregnancy prevention, early diagnosis of pregnancy, accurate
      assessment of gestation, standardization and supply of MVA technology, and simple
      and affordable regimens for medical abortion.

PMID- 15147857
TI  - New and underutilized technologies to reduce maternal mortality: call to action
      from a Bellagio workshop.
AB  - Little progress has been made in preventing the more than 500,000 maternal deaths
      that occur each year. Many new and underutilized technologies can be used to
      reduce these deaths. In July 2003, maternal health experts from around the world
      gathered in Bellagio, Italy, to develop a set of priority actions for reducing
      maternal mortality using proven and promising technologies. To reduce maternal
      mortality, immediate efforts are needed to accelerate the appropriate use of
      technologies and to reduce their inequitable distribution. Organizations are
      called on to commit the necessary human and financial resources to evaluate and
      document the effectiveness of promising technologies and to scale up and put
      proven technologies into widespread use to save women's lives.

PMID- 15147858
TI  - Biotic and heavy metal stress response in plants: evidence for common signals.
AB  - In higher plants, biotic stress (e.g., herbivore or pathogen attack) as well as
      abiotic stress (in particular heavy metals) often induce the synthesis and
      accumulation of the same defense-related secondary metabolites. This well-known
      finding still awaits an explanation regarding the common features of both stress
      types. In this study, a mechanism is proposed that links reactive oxygen species
      (ROS) generation with lipid oxidation processes, ultimately resulting in the
      formation of similar, highly active signalling compounds. The generation of ROS
      is a common event in both heavy metal treatment and biotic stress although it can
      depend on quite different, enzymatic and non-enzymatic reactions. Regardless, ROS
      are involved in the oxidation of unsaturated fatty acids which initiate the
      formation of oxylipins, a highly variable class of lipid-derived compounds in
      plants. Oxylipins represent new endogenous signals involved in biotic- and
      abiotic-induced stress responses.

PMID- 15147859
TI  - Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes.
AB  - Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG
      autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained
      from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition
      to desmoglein-3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG
      autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of
      cell-cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in
      cells treated with autoantibodies compared to those treated with normal
      antibodies. The apoptotic process induced by IgG autoantibodies was characterized
      by caspase-3 activation, Bcl-2 depletion and Bax expression. The present report
      demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes.

PMID- 15147860
TI  - A novel family of carbohydrate-binding modules identified with Ruminococcus albus
      proteins.
AB  - We recently showed that some of the enzymes underpinning cellulose solubilization
      by Ruminococcus albus 8 lack the conventional type of dockerin module
      characteristic of cellulosomal proteins and instead, bear an "X" domain of
      unknown function at their C-termini. We have now subcloned and expressed six X
      domains and showed that five of them bind to xylan, chitin, microcrystalline and
      phosphoric-acid swollen cellulose, as well as more heterogenous substrates such
      as alfalfa cell walls, banana stem and wheat straw. The X domain that did not
      bind to these substrates was derived from a family-5 glycoside hydrolase (Cel5G),
      which possesses two X domains in tandem. Whereas the internal X domain failed to
      bind to the substrates, the recombinant dyad exhibited markedly enhanced binding
      relative to that observed for the C-terminal X domain alone. The evidence
      supports a distinctive carbohydrate-binding role of broad specificity for this
      type of domain, and we propose a novel family (designated family 37) of
      carbohydrate-binding modules that appear to be peculiar to R. albus.

PMID- 15147861
TI  - Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T15.
AB  - We have cloned, expressed and characterized a novel member of the human UDP
      GalNAc:polypeptide N-acetylgalactosaminyltransferase (pp-GalNAc-T) family, pp
      GalNAc-T15. The pp-GalNAc-T15 transcript was ubiquitously expressed in human
      tissues. Recombinant pp-GalNAc-T15 transferred N-acetylgalactosamine (GalNAc)
      toward a panel of mucin-derived peptide substrates in vitro. Although pp-GalNAc
      T15 showed significantly less catalytic activity than pp-GalNAc-T2, T15
      transferred up to seven GalNAcs to the Muc5AC peptide, while T2 transferred up to
      five GalNAcs. These results clearly indicated that pp-GalNAc-T15 is a novel
      member of the human pp-GalNAc-T family with unique catalytic activity.

PMID- 15147862
TI  - Cholesterol perturbing agents inhibit NMDA-dependent calcium influx in rat
      hippocampal primary culture.
AB  - The present study was carried out to investigate the potential involvement of
      cholesterol-rich membrane microdomains in the mobilization of calcium induced by
      NMDA-receptors (NMDA-R). We herein provide evidence that agents interfering with
      plasma membrane cholesterol (namely, filipin and methyl-beta-cyclodextrin (Cdex))
      inhibit the NMDA-stimulated influx of calcium in hippocampal cells in culture.
      Filipin-treated cells maintained their morphology and were able to respond with a
      calcium influx to high K(+) challenge, whereas Cdex altered both cellular
      parameters. These results suggest that the NMDA-R can be located in cholesterol
      rich membrane microdomains or alternatively that the mechanisms coupling their
      dynamics in the post-synaptic membrane are dependent on the integrity of the
      microdomains.

PMID- 15147863
TI  - Molecular analysis of the interaction between palladin and alpha-actinin.
AB  - Palladin is a novel component of stress fiber dense regions. Antisense and
      transient overexpression studies have indicated an important role for palladin in
      the regulation of actin cytoskeleton. Palladin colocalizes and
      coimmunoprecipitates with alpha-actinin, a dense region component, but the
      molecular details and functional significance of the interaction have not been
      studied. We show here a direct association between the two proteins and have
      mapped the binding site within a short sequence of palladin and in the carboxy
      terminal calmodulin domain of alpha-actinin. Using transfection-based targeting
      assays, we show that palladin is involved in targeting of alpha-actinin to
      specific subcellular foci indicating a functional interplay between the two actin
      associated proteins.

PMID- 15147865
TI  - Double-strand break of giant DNA: protection by glucosyl-hesperidin as evidenced
      through direct observation on individual DNA molecules.
AB  - We have performed a real-time observation of photo-induced breakage on individual
      long DNA molecules stained by a cyanine dye, YOYO, under the intense illumination
      (lambda=450-490 nm) in solution. It was shown that the double-strand breakage is
      accelerated by Fenton's reagent (Fe2+/H2O2). In addition, it was found that the
      breakage reaction is protected in the presence of a water-soluble flavonoid,
      glucosyl-hesperidin. To interpret the kinetic process of the double-strand
      breakage reaction, a two-step mechanism is proposed: under light illumination on
      giant DNA molecules, single-strand breaks are generated to induce nicks in a
      stochastic manner, and then reactive oxygen attacks these nicks causing the
      double-strand break.

PMID- 15147864
TI  - Bisperoxovanadium compounds are potent PTEN inhibitors.
AB  - The tumour suppressor phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) shares homology with protein tyrosine phosphatases (PTPases). Similarly,
      bisperoxovanadium (bpV) molecules that are well-established PTPase inhibitors
      were shown to inhibit PTEN, but at up to 100-fold lower concentrations. The
      preference and potency of the bpVs towards PTEN was validated in vivo as
      demonstrated by: (i) an increase of Ser473 phosphorylation of protein kinase B
      (PKB) at similar low nanomolar doses, (ii) the lack of any effect on the PKB
      phosphorylation in the PTEN negative cell line UM-UC-3, (iii) the ability to
      rescue Ly294002-induced phosphoinositide 3-kinase inhibition and (iv) a lack of
      tyrosine phosphorylation at low nanomolar doses.

PMID- 15147866
TI  - The steroid receptor RNA activator is the first functional RNA encoding a
      protein.
AB  - The steroid receptor RNA activator (SRA) has previously been characterized as
      belonging to the growing family of functional non-coding RNAs. However, we
      recently reported the Western blot detection of a putative endogenous SRA protein
      (SRAP) in breast cancer cells. Herein, we successfully suppressed the expression
      of this protein through specific RNA interference assay, unequivocally confirming
      its existence. Moreover, using database searches and Western blot analysis, we
      also showed that SRAP is highly conserved among chordata. Overall, our results
      suggest that SRA is the first example of a new class of functional RNAs also able
      to encode a protein.

PMID- 15147867
TI  - A tradeoff between protein stability and conformational mobility in homotrimeric
      dUTPases.
AB  - Oligomerization directs active site formation in homotrimeric 2'-deoxyuridine
      triphosphate pyrophosphatases (dUTPases). Stability of the homotrimer is a
      central determinant in enzyme function. The present comparative studies of
      bacterial and fruitfly dUTPases with homologous 3D structures by differential
      scanning microcalorimetry; fluorescence, circular dichorism and infrared
      spectroscopies, demonstrate that unfolding is a two-state highly cooperative
      transition in both dUTPases excluding a significantly populated intermediate
      state of dissociated and folded monomers. The eukaryotic protein is much less
      resistant against either thermal or guanidine hydrochloride-induced denaturation.
      Results suggest that hydrophobic packing of the inner threefold channel of the
      dUTPase homotrimer greatly contributes to stability.

PMID- 15147868
TI  - Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1.
AB  - Transforming growth factor-beta (TGF-beta), a multifunctional cytokine which is
      involved in extracellular matrix modulation, has a major role in the pathogenesis
      and progression of fibrotic diseases. We now report the effects of ursolic acid
      on TGF-beta1 receptor binding and TGF-beta1-induced cellular functions in vitro.
      Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse
      fibroblasts with an IC(50) value of 6.9+/-0.8 microM. Ursolic acid dose
      dependently recovered reduced proliferation of Minc Mv1Lu cells in the presence
      of 5 nM of TGF-beta1 and attenuated TGF-beta1-induced collagen synthesis and
      production in human fibroblasts. Molecular dynamics simulations suggest that
      ursolic acid may interact with the hydrophobic region of the dimeric interface
      and thereby inhibit the binding of TGF-beta1 to its receptor. All these findings
      taken together show that ursolic acid functions as an antagonist for TGF-beta1.
      This is the first report to show that a small molecule can inhibit TGF-beta1
      receptor binding and influence functions of TGF-beta1.

PMID- 15147869
TI  - Involvement of GSK-3beta in TWEAK-mediated NF-kappaB activation.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a key component of several
      signaling pathways. We found that a short variant of 'TNF-like weak inducer of
      apoptosis' (shortTWEAK) formed a complex with GSK-3beta in a yeast two-hybrid
      system. We demonstrate that shortTWEAK and GSK-3beta colocalize in the nucleus of
      human neuroblastoma cells. We also show that TWEAK is internalized in different
      cell lines and that it translocates to the nucleus. This event causes the
      degradation of IkappaBalpha, the nuclear translocation of both GSK-3beta and p65,
      and the induction of NF-kappaB-driven gene expression. We demonstrate that the
      induction of IL-8 expression by TWEAK can be counteracted by LiCl. Taken
      together, these data suggest that GSK-3beta plays an important role in the signal
      transduction pathway between TWEAK and NF-kappaB.

PMID- 15147870
TI  - Cellular cholesterol regulates MT1 MMP dependent activation of MMP 2 via MEK-1 in
      HT1080 fibrosarcoma cells.
AB  - Unstimulated human fibrosarcoma cells (HT1080) constitutively secrete matrix
      metalloproteinase 2 (MMP 2) as a proenzyme requiring proteolytic cleavage by
      membrane type-1 MMP (MT1 MMP) for activation. Physiological and pharmacological
      stimuli induce clustering of MT1 MMP/tissue inhibitor of MMP 2 "receptors",
      promoting binding and activation of MMP 2. We now report that cholesterol
      depleted HT1080 cells accumulated MT1 MMP on the cell surface and activated MMP
      2. A specific inhibitor of mitogen activated protein kinase kinase 1/2 inhibited
      both MMP 2 activation and extracellular signal-related kinase phosphorylation
      induced by cholesterol depletion. Our data indicate that the cholesterol content
      of unstimulated cells is critical for secretion of MMP 2 as an inactive zymogen
      and control of pericellular proteolysis.

PMID- 15147871
TI  - Expression of NUDEL in manchette and its implication in spermatogenesis.
AB  - Nuclear distribution gene E-like product (NUDEL) is a mammal homologue of fungal
      NUDE and is involved in neuronal migration during brain development. High levels
      of NUDEL were expressed in murine testis as well as brain. During
      spermatogenesis, NUDEL was not detected until postnatal day 12 (P12), rising to
      significant levels at P27. NUDEL was localized predominantly along microtubules
      of the manchette in elongated spermatids. In maturing spermatids, NUDEL was
      observed only in the centrosomes, while mature testicular spermatozoa did not
      show any NUDEL expression. These results suggest that NUDEL plays an important
      role in germ cell formation, including nucleoplasmic transport and nucleus
      shaping by manchette microtubules.

PMID- 15147872
TI  - Fission yeast Skp1 is required for spindle morphology and nuclear membrane
      segregation at anaphase.
AB  - Skp1 is a core component of the Skp1-Cullin-1-F-box ubiquitin ligase. Here, we
      show a novel role for fission yeast Skp1 in mitotic progression. Temperature
      sensitive skp1-A7 mutants enter mitosis, but fail to execute anaphase. Time-lapse
      imaging shows that spindles in this mutant form intranuclear arch-like
      structures, which eventually collapse abruptly. The two spindle poles are also
      seen to move backward to the cell centre rather than towards the cell ends. These
      abnormal phenotypes appear to stem from defects in nuclear membrane segregation.
      Our results show that Skp1 is required for coordinated structural alterations of
      mitotic spindles and nuclear membranes.

PMID- 15147873
TI  - The H(+)-dependent reduced folate carrier 1 of humans and the sodium-dependent
      methotrexate carrier-1 of the rat are orthologs.
AB  - Previously, two different carrier systems for uptake of reduced folates and the
      antifolate methotrexate (Mtx) were described: the pH-dependent folate sensitive
      reduced folate carrier 1 (RFC1) from human, hamster and mouse and a sodium
      dependent and folate insensitive Mtx carrier-1 (MTX-1) from rat. It was found
      that all critical residues of the homologous amino acid sequence were identical.
      RFC1- as well as MTX-1-mediated uptake of a marker substrate into suitable human
      and rat cell lines increased with proton concentration, was sodium-dependent at
      neutral pH, and inhibited by folate at acidic pH. It is concluded that RFC1 and
      MTX-1 are orthologs.

PMID- 15147874
TI  - The promoter of brain-specific angiogenesis inhibitor 1-associated protein 4
      drives developmentally targeted transgene expression mainly in adult cerebral
      cortex and hippocampus.
AB  - Restricting transgene expression to specific cell types and maintaining long-term
      expression are major goals for gene therapy. Previously, we cloned brain-specific
      angiogenesis inhibitor 1-associated protein 4 (BAI1-AP4), a novel brain-specific
      protein that interacts with BAI1, and found that it was developmentally
      upregulated in the adult brain. In this report, we isolated 5 kb of the 5'
      upstream sequence of the mouse BAI1-AP4 gene and analyzed its promoter activity.
      Functional analyses demonstrated that an Sp1 site was the enhancer, and the
      region containing the transcription initiation site and an AP2-binding site was
      the basal promoter. We examined the ability of the BAI1-AP4 promoter to drive
      adult brain-specific expression by using it to drive lacZ expression in
      transgenic (TG) mice. Northern blot analyses showed a unique pattern of beta
      galactosidase expression in TG brain, peaking at 1 month after birth, like
      endogenous BAI1-AP4. Histological analyses demonstrated the same localization and
      developmental expression of beta-galactosidase and BAI1-AP4 in most neurons of
      the cerebral cortex and hippocampus. Our data indicate that TG mice carrying the
      BAI1-AP4 promoter could be a valuable model system for region-specific brain
      diseases.

PMID- 15147875
TI  - Reshaping the folding energy landscape by chloride salt: impact on molten-globule
      formation and aggregation behavior of carbonic anhydrase.
AB  - During chemical denaturation different intermediate states are populated or
      suppressed due to the nature of the denaturant used. Chemical denaturation by
      guanidine-HCl (GuHCl) of human carbonic anhydrase II (HCA II) leads to a three
      state unfolding process (Cm,NI=1.0 and Cm,IU=1.9 M GuHCl) with formation of an
      equilibrium molten-globule intermediate that is stable at moderate concentrations
      of the denaturant (1-2 M) with a maximum at 1.5 M GuHCl. On the contrary, urea
      denaturation gives rise to an apparent two-state unfolding transition (Cm=4.4 M
      urea). However, 8-anilino-1-naphthalene sulfonate (ANS) binding and decreased
      refolding capacity revealed the presence of the molten globule in the middle of
      the unfolding transition zone, although to a lesser extent than in GuHCl. Cross
      linking studies showed the formation of moderate oligomer sized (300 kDa) and
      large soluble aggregates (>1000 kDa). Inclusion of 1.5 M NaCl to the urea
      denaturant to mimic the ionic character of GuHCl leads to a three-state unfolding
      behavior (Cm,NI=3.0 and Cm,IU=6.4 M urea) with a significantly stabilized molten
      globule intermediate by the chloride salt. Comparisons between NaCl and LiCl of
      the impact on the stability of the various states of HCA II in urea showed that
      the effects followed what could be expected from the Hofmeister series, where Li+
      is a chaotropic ion leading to decreased stability of the native state. Salt
      addition to the completely urea unfolded HCA II also led to an aggregation prone
      unfolded state, that has not been observed before for carbonic anhydrase.
      Refolding from this state only provided low recoveries of native enzyme.

PMID- 15147876
TI  - Expression of Bax in yeast affects not only the mitochondria but also vacuolar
      integrity and intracellular protein traffic.
AB  - Bax-induced lethality in yeast is accompanied by morphological changes in
      mitochondria, giving rise to a reduced number of swollen tubules. Although these
      changes are completely abolished upon coexpression of the Bax inhibitor, Bcl-2,
      coexpression of Bax with Bax inhibiting-glutathione S-transferase (BI-GST) leads
      to aggregation, but not fusion of the mitochondria. In addition, Bax affects the
      integrity of yeast vacuoles, resulting in the disintegration and eventual loss of
      the organelles, and the disruption of intracellular protein traffic. While Bcl-2
      coexpression only partially corrects this phenotype, coexpression of BI-GST fully
      restores the organelles, indicating a different mode of protection exerted by Bcl
      2 and BI-GST.

PMID- 15147877
TI  - The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase results in reduced enzyme activities but not in altered
      overall cellular sialylation in hereditary inclusion body myopathy.
AB  - Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by
      mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the
      key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single
      homozygous mutation occurs, converting methionine-712 to threonine. Recombinant
      expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine
      kinase activity, in agreement with the localization of the mutation within the
      kinase domain. B lymphoblastoid cell lines derived from patients expressing the
      mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase activity.
      Nevertheless, no reduced cellular sialylation was found in those cells by
      colorimetric assays and lectin analysis, indicating that HIBM is not directly
      caused by an altered overall expression of sialic acids.

PMID- 15147879
TI  - Regulation of phosphatidylcholine biosynthesis under salt stress involves choline
      kinases in Arabidopsis thaliana.
AB  - Increasing evidence suggests a major role for phosphatidylcholine (PC) in plant
      stress adaptation. The present work investigated the regulation of choline, PC
      and interconnected phosphatidylethanolamine biosynthesis in Arabidopsis thaliana
      L. as a function of cold- and salt- or mannitol-mediated hyperosmotic stresses.
      While PC synthesis is accelerated in both salt- and cold-treated plants, the
      choline kinase (CK) and phosphocholine cytidylyltransferase genes are oppositely
      regulated with respect to these abiotic treatments. Salt stress also stimulates
      CK activity in vitro. A possible regulatory role of CK in stimulating PC
      biosynthesis rate in salt-stressed plants is discussed.

PMID- 15147878
TI  - Ubiquilin interacts with ubiquitylated proteins and proteasome through its
      ubiquitin-associated and ubiquitin-like domains.
AB  - Mammalian cells acquire tolerance against multiple stressors through the high
      level expression of stress-responsible genes. We have previously demonstrated
      that protein-disulfide isomerase (PDI) together with ubiquilin are up-regulated
      in response to hypoxia/brain ischemia, and play critical roles in resistance to
      these damages. We show here that ubiquilin interacts preferentially with poly
      ubiquitin chains and 19S proteasome subunits. Taken together, these results
      suggest that ubiquitin could serve as an adaptor protein that both interacts with
      PDI and mediates the delivery of poly-ubiquitylated proteins to the proteasome in
      the cytosol in the vicinity of the endoplasmic reticulum membrane.

PMID- 15147880
TI  - Co-localization of CD3 and prion protein in Jurkat lymphocytes after hypothermal
      stimulation.
AB  - While long-term effects of temperature treatment in respect of, e.g., gene
      expression and cellular function have already been studied in some detail,
      nothing is known on the physiological responses of lymphocytes during short-term
      hypothermal shifts. In this report, we characterized the effects of such a
      stimulation using the human lymphocyte cell line Jurkat E6.1 and present evidence
      that warming from 4 to 37 degrees C for only 2 min is sufficient to cause co
      localization of CD3, prion protein and the lipid-raft ganglioside GM1 paralleling
      lymphocyte activation as observed by Ca(2+) mobilization and mitogen-activated
      protein kinase-phosphorylation.

PMID- 15147881
TI  - Proton pumping mechanism and catalytic cycle of cytochrome c oxidase: Coulomb
      pump model with kinetic gating.
AB  - Using electrostatic calculations, we have examined the dependence of the
      protonation state of cytochrome c oxidase from bovine heart on its redox state.
      Based on these calculations, we propose a possible scheme of redox-linked proton
      pumping. The scheme involves His291 - one of the ligands of the Cu(B) redox
      center - which plays the role of the proton loading site (PLS) of the pump. The
      mechanism of pumping is based on ET reaction between two hemes of the enzyme,
      which is coupled to a transfer of two protons. Upon ET, the first proton (fast
      reaction) is transferred to the PLS (His291), while subsequent transfer of the
      second "chemical" proton to the binuclear center (slow reaction) is accompanied
      by the ejection of the first (pumped) proton. Within the proposed model, we
      discuss the catalytic cycle of the enzyme.

PMID- 15147882
TI  - Organization of telomeric nucleosomes: atomic force microscopy imaging and
      theoretical modeling.
AB  - Telomeric chromatin has peculiar features with respect to bulk chromatin, which
      are not fully clarified to date. Nucleosomal arrays, reconstituted on fragments
      of human telomeric DNA and on tandemly repeated tetramers of 5S rDNA, have been
      investigated at single-molecule level by atomic force microscopy and Monte Carlo
      simulations. A satisfactory correlation emerges between experimental and
      theoretical internucleosomal distance distributions. However, in the case of
      telomeric nucleosomal arrays containing two nucleosomes, we found significant
      differences. Our results show that sequence features of DNA are significant in
      the basic chromatin organization, but are not the only determinant.

PMID- 15147884
TI  - Yap8p activation in Saccharomyces cerevisiae under arsenic conditions.
AB  - Yap8p, a member of the Saccharomyces cerevisiae Yap family, is activated in
      response to arsenic. Both the mechanisms by which this activation takes place and
      its regulation have not yet been identified. In this report, we show that Yap8p
      is not activated at the transcriptional level but, rather, its nuclear transport
      is actively regulated and dependent on the exportin chromosome region maintenance
      protein. In addition, it is shown that Cys(132), Cys(137)and Cys(274) are
      essential for Yap8p localization and transactivation function both of which are
      required for its biological activity.

PMID- 15147883
TI  - Identification of chloride intracellular channel proteins in spermatozoa.
AB  - We have identified for the first time the presence of chloride intracellular
      channel (CLIC) proteins in bovine epididymal spermatozoa. CLIC1 was discovered
      during microsequencing of proteins that co-purified with protein phosphatase 1,
      PP1gamma2, in sperm extracts. In addition to CLIC1, Western blot showed that two
      additional CLIC family members, CLIC4 and CLIC5, are also present in spermatozoa.
      CLIC fusion proteins, GST-CLIC1, GST-CLIC4 and GST-CLIC5, were all able to bind
      to PP1gamma2 in sperm extracts during pull-down assays. Immunofluorescence
      microscopy revealed that each of the three isoforms occupies a distinct location
      within the cell. Given that PP1gamma2 is a key enzyme regulating sperm motility,
      PP1gamma2-binding proteins, such as the CLIC proteins, are likely to play
      significant roles in sperm function.

PMID- 15147885
TI  - Evidence of finely tuned expression of DNA polymerase beta in vivo using
      transgenic mice.
AB  - DNA polymerase (Pol) is an error-prone repair DNA polymerase that has been shown
      to create genetic instability and tumorigenesis when overexpressed by only 2-fold
      in cells, suggesting that a rigorous regulation of its expression may be
      essential in vivo. To address this question, we have generated mice which express
      a transgene (Tg) bearing the Pol cDNA under the control of the ubiquitous
      promoter of the mouse H-2K gene from the major histocompatibility complex. These
      mice express the Tg only in thymus, an organ which normally contains the most
      abundant endogenous Pol mRNA and protein, supporting the idea of a tight
      regulation of Pol in vivo. Furthermore, we found no tumor incidence, suggesting
      that the single Pol overexpression event is not sufficient to initiate
      tumorigenesis in vivo.

PMID- 15147886
TI  - Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis
      proteins (c-IAP1 and c-IAP2) in vitro.
AB  - Receptor interacting protein (RIP) is recruited to tumor necrosis factor-alpha
      receptor 1 (TNFR1) complex upon stimulation and plays a crucial role in the
      receptor-mediated NF-kappaB activation. Among the components of the TNFR1 complex
      are proteins that possess ubiquitin-protein isopeptide ligase (E3) activities,
      such as TNFR1-associated factor 2 (TRAF2), cellular inhibitor of apoptosis
      proteins (c-IAPs) namely, c-IAP1 and c-IAP2. Here, we showed that ectopically
      expressed RIP is ubiquitinated, and either the intermediate or death domain of
      RIP is required for this modification. Expression of c-IAP1 and c-IAP2 decreased
      the steady-state level of RIP, which was blocked by inhibition of the 26S
      proteasome. RIP degradation requires intact c-IAP2 containing the RING domain.
      Our in vitro ubiquitination assay revealed that while TRAF2 had no effect, both c
      IAP1 and c-IAP2-mediated RIP ubiquitination with similar efficiency, indicating
      that c-IAPs can function as E3 toward RIP.

PMID- 15147887
TI  - Paramagnetic NMR study of Cu(2+)-IDA complex localization on a protein surface
      and its application to elucidate long distance information.
AB  - The paramagnetic metal chelate complex Cu(2+)-iminodiacetic acid (Cu(2+)-IDA) was
      mixed with ubiquitin, a small globular protein. Quantitative analyses of (1)H and
      (15)N chemical shift changes and line broadenings induced by the paramagnetic
      effects indicated that Cu(2+)-IDA was localized to a histidine residue (His68) on
      the ubiquitin surface. The distances between the backbone amide proton and the
      Cu(2+) relaxation center were evaluated from the proton transverse relaxation
      rates enhanced by the paramagnetic effect. These correlated well with the
      distances calculated from the crystal structure up to 20 A. Here, we show that a
      Cu(2+)-IDA is the first paramagnetic reagent that specifically localizes to a
      histidine residue on the protein surface and gives the long-range distance
      information.

PMID- 15147888
TI  - A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by
      GSK3beta and is highly expressed in brain tumors.
AB  - To explore more hNinein interacting proteins, the yeast two-hybrid screening
      using ninein C-terminal domain as bait protein was performed. One novel gene, CGI
      99, was demonstrated to associate with hNinein in the yeast two-hybrid method and
      in vitro GST pull-down assay. Molecular characterization also showed that CGI-99
      possessed a transcriptional activity at the N-terminal. In addition, CGI-99
      formed a dimer with the C-terminal, which overlapped with hNinein binding site.
      In kinase assay, CGI-99 binds to hNinein and completely blocks the
      phosphorylation of hNinein by GSK3beta. Moreover, CGI-99 was highly expressed in
      all brain tumors which is in agreement with the Northern blot analysis. Taken
      together, we have isolated a novel protein CGI-99, which may be involved in the
      functional regulation of human ninein in the centrosome structure and may also be
      important in brain development and tumorigenesis.

PMID- 15147889
TI  - Expression of estrogen receptor beta in prostate carcinoma cells inhibits
      invasion and proliferation and triggers apoptosis.
AB  - The involvement of estrogen receptor beta (ERbeta) in prostate carcinogenesis has
      been hypothesized. Several reports have shown that ERbeta expression was
      decreased when prostate cells undergo neoplastic transformation, suggesting that
      it could play a tumor-suppressor role. By restoring ERbeta expression in
      prostatic carcinoma cells by adenoviral delivery, we aimed to test this
      hypothesis. We observed that ERbeta strongly inhibited the invasiveness and the
      growth of these cells. In addition, ERbeta cells were undergoing apoptosis, as
      shown by quantification of Bax, poly(ADP-ribose) polymerase and caspase-3
      expression. Our data suggest that ERbeta acts as a tumor-suppressor by its anti
      proliferative, anti-invasive and pro-apoptotic properties.

PMID- 15147891
TI  - Cytosolic sialidase Neu2 upregulation during PC12 cells differentiation.
AB  - The cytosolic sialidase Neu2 is known to be involved in myoblast differentiation.
      Here, we observed a Neu2 transcriptional induction during nerve growth factor,
      fibroblast growth factor 2 and epidermal growth factor treatments of PC12 cells,
      a favored model to study neuronal differentiation. The expression analysis of
      Neu2 deleted promoter revealed a remarkable increase of luciferase activity in
      treated PC12 cells, suggesting that in this cell line the Neu2 transcriptional
      levels are highly regulated. The enzymatic activity of cytosolic sialidase Neu2
      was found to increase transiently only during differentiation, whereas was
      undetectable in untreated PC12 cells. These data suggest a possible involvement
      of cytosolic sialidase Neu2 in differentiation of PC12 cells.

PMID- 15147890
TI  - The farnesoid X receptor induces very low density lipoprotein receptor gene
      expression.
AB  - The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids
      (BAs). In response to ligand-binding, FXR regulates many genes involved in BA,
      lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray
      technology was used to profile total RNA extracted from HepG2 cells treated with
      the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a
      significant increase of transcript level of the very low density lipoprotein
      receptor (VLDLR) was observed. Our data, resulting from selective FXR activation,
      FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up
      regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human
      and in vivo in mouse liver cells.

PMID- 15147892
TI  - NF-kappaB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK
      pathway.
AB  - 4-Hydroxyhexenal (HHE) is known to affect redox balance during aging, included
      are vascular dysfunctions. To better understand vascular abnormality through the
      molecular alterations resulting from HHE accumulation in aging processes, we set
      out to determine whether up-regulation of mitogen-activated protein kinase (MAPK)
      by HHE is mediated through nuclear factor kappa B (NF-kappaB) activation in
      endothelial cells. HHE induced NF-kappaB activation by inhibitor of kappaB
      (IkappaB) phosphorylation via the IkappaB kinase (IKK)/NF-kappaB inducing kinase
      (NIK) pathway. HHE increased the activity of p38 MAPK and extracellular signal
      regulated kinase (ERK), but not c-jun NH(2)-terminal kinase, indicating that p38
      MAPK and ERK are closely involved in HHE-induced NF-kappaB transactivation.
      Pretreatment with ERK inhibitor PD98059, and p38 MAPK inhibitor SB203580,
      attenuated the induction of p65 translocation, IkappaB phosphorylation, and NF
      kappaB luciferase activity. These findings strongly suggest that HHE induces NF
      kappaB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation
      associated with oxidative stress in endothelial cells.

PMID- 15147893
TI  - Streptococcal antigen I/II binds to extracellular proteins through intermolecular
      beta-sheets.
AB  - One of the functions associated with the oral streptococcal surface protein I/II
      is to bind to human extracellular matrix molecules or blood components, which
      could act as opportunistic ligands in pathological circumstances. In order to
      understand the relative specificity of the binding repertoire of this bacterial
      adhesin, we examined by infrared measurements the mode of binding of the protein
      I/II from Streptococcus mutans OMZ175 (I/IIf) to fibronectin and fibrinogen. This
      approach revealed the beta-structure forming capacity of I/IIf upon interaction
      with both proteins. The forming of intermolecular beta-structures may provide a
      non-selective way of interaction between I/IIf and its possible targets.

PMID- 15147894
TI  - Staphylococcus aureus peptidoglycan stimulates granulocyte macrophage colony
      stimulating factor production from human epidermal keratinocytes via mitogen
      activated protein kinases.
AB  - Epidermal keratinocytes with atopic dermatitis (AD) overproduce mediators such as
      granulocyte macrophage colony-stimulating factor (GM-CSF), which are associated
      with pathology of AD. We found that peptidoglycan (PGN) of Staphylococcus aureus,
      which is frequently observed in lesion with AD, induced the production of
      numerous mediators such as GM-CSF and regulated on activation, normal T-cell
      expressed and secreted. Moreover, PGN phosphorylated extracellular-signal
      regulated kinases and p38 mitogen-activated protein kinase, which were involved
      in the induction of GM-CSF expression. These results suggested that PGN of S.
      aureus directly exacerbates inflammation of inflammatory skin disease.

PMID- 15147896
TI  - The mature part of proNGF induces the structure of its pro-peptide.
AB  - Human nerve growth factor (NGF) belongs to the structural family of cystine knot
      proteins, characterized by a disulfide pattern in which one disulfide bond
      threads through a ring formed by a pair of two other disulfides connecting two
      adjacent beta-strands. Oxidative folding of NGF revealed that the pro-peptide of
      NGF stimulates in vitro structure formation. In order to learn more about this
      folding assisting protein fragment, a biophysical analysis of the pro-peptide
      structure has been performed. While proNGF is a non-covalent homodimer, the
      isolated pro-peptide is monomeric. No tertiary contacts stabilize the pro-peptide
      in its isolated form. In contrast, the pro-peptide appears to be structured when
      bound to the mature part. The results presented here demonstrate that the mature
      part stabilizes the structure in the pro-peptide region. This is the first report
      that provides a biophysical analysis of a pro-peptide of the cystine knot protein
      family.

PMID- 15147895
TI  - Neocarzinostatin naphthoate synthase: an unique iterative type I PKS from
      neocarzinostatin producer Streptomyces carzinostaticus.
AB  - Enediyne antibiotics are known for their potent antitumor activities. One such
      enediyne, neocarzinostatin (NCS), consists of a 1:1 complex of non-peptide
      chromophore (1a), and peptide apoprotein. The structurally diverse non-peptide
      chromophore is responsible for its biological activity. One of its structural
      components, the naphthoic acid moiety (2,7-dihydroxy-5-methyl-1-naphthoic acid,
      1d) is synthesized by a polyketide synthase (PKS) pathway through condensing six
      intact acetate units. The 5.45 kb iterative type I PKS, neocarzinostatin
      naphthoate synthase (NNS), responsible for naphthoic acid moiety biosynthesis,
      shares sequence homology with 6-methyl salicylic acid synthase of fungi and
      orsellinic acid synthases (AviM and CalO5) of Streptomyces origin. Cultures of S.
      lividans TK24 and S. coelicolor YU105 containing plasmids with NNS were able to
      produce 2-hydroxy-5-methyl-1-naphthoic acid (2a), a key intermediate of naphthoic
      acid moiety in NCS. In addition to 2a, a novel product, 2-hydroxy-5-hydroxymethyl
      1-naphthoic acid (2d) was isolated. This is the first report of a bacterial
      iterative type I PKS from an enediyne producer which enables the biosynthesis of
      bicyclic aromatic compounds.

PMID- 15147897
TI  - Sites of positive allosteric modulation by neurosteroids on ionotropic gamma
      aminobutyric acid receptor subunits.
AB  - Neurosteroids are known as allosteric modulators of ionotropic gamma-aminobutyric
      acid (GABA) receptors. Here, we investigated sites of positive allosteric
      modulation by allotetrahydrodeoxycorticosterone (5alpha-THDOC) at GABA receptors
      using the technique of chimeragenesis and the Xenopus oocyte expression system.
      Our findings have demonstrated that the region from transmembrane segment (TM) 4
      to the C-terminus of the GABA(A) receptor alpha1 subunit is crucial for the
      action of 5alpha-THDOC, but insufficient for the action of another neurosteroid
      allopregnanolone, suggesting that a specific region critical for neurosteroid
      action at GABA receptors exists in the domain between TM4 and the C-terminus of
      GABA receptor subunits.

PMID- 15147898
TI  - Complementation of Saccharomyces cerevisiae ccc2 mutant by a putative P1B-ATPase
      from Brassica napus supports a copper-transporting function.
AB  - Copper transport across membranes plays an important role in plant growth and
      survival. P(1B)-type ATPases participate in transmembrane transport of copper in
      various organisms. A Brassica napus cDNA (BnRAN1) encoding a putative Cu(2+)
      ATPase was cloned in this study. A complementation assay demonstrated that the
      protein encoded by this cDNA could functionally replace Ccc2p, a Saccharomyces
      cerevisiae Cu(2+)-ATPase, rescuing growth of ccc2 mutant under iron-limited
      conditions. Our results suggest that this rescue likely resulted from restoration
      of copper delivery, mediated by BnRAN1, to Fet3p. This study is amongst the first
      to demonstrate that a putative plant P(1B)-ATPase is functional and to examine
      its substrate specificity.

PMID- 15147899
TI  - Effectiveness of RNA interference in transgenic plants.
AB  - RNA interference (RNAi) can be used to study gene function by effecting
      degradation of the targeted transcript. However, the effectiveness of transgene
      induced RNAi among multiple target genes has not been compared systematically. To
      this end, we developed a relative quantitative RT-PCR protocol that allows use of
      a single internal standard over a wide range of target gene expression levels.
      Using this method in an analysis of transgenic Arabidopsis thaliana RNAi lines
      targeting 25 different endogenes revealed that independent, homozygous, single
      copy (sc) T4 lines targeting the same gene generally reduce transcript levels to
      the same extent, whereas multi-copy RNAi lines differed in the degree of target
      reduction and never exceeded the effect of sc transgenes. The maximal reduction
      of target transcript levels varied among targets. These observations suggest that
      each target sequence possesses an inherent degree of susceptibility to dsRNA
      mediated degradation.

PMID- 15147900
TI  - The TRAF6 RING finger domain mediates physical interaction with Ubc13.
AB  - Tumor necrosis factor receptor associated factor 6 (TRAF6) is an important
      signaling molecule involved in a diverse array of physiological processes. It has
      been proposed that TRAF6, a RING finger-containing protein, acts as a ubiquitin
      ligase (E3) and a target for Lys-63 linked polyubiquitination mediated by Ubc13
      Uev, a ubiquitin conjugating (E2) complex. However, the physical interaction
      between TRAF6 and this E2 complex has not been reported. We used the yeast two
      hybrid assay to demonstrate that TRAF6 indeed interacts with the E2 complex
      through its direct binding to Ubc13. Either a single Cys-to-Ser substitution
      within the TRAF6 RING finger domain or an amino acid substitution on the Ubc13
      surface, that is predicted to interact with RING finger proteins, is able to
      abolish the interaction. In addition, we found that TRAF6 can interact with
      itself and this self-interaction domain is mapped to the N-terminus containing
      the RING finger motif. Based on this study and our previous Ubc13-Uev structural
      analysis, the interface of Ubc13-TRAF6 RING finger can be predicted.

PMID- 15147901
TI  - Characterization of splice variants of human caspase-activated DNase with CIDE-N
      structure and function.
AB  - Internucleosomal DNA fragmentation is an apoptotic event that depends on the
      activity of different nucleases. Among them, the DNA fragmentation factor B,
      better known as caspase-activated DNase (CAD), is mainly responsible for this DNA
      fragmentation in dying cells. CAD is an endonuclease that is chaperoned and
      inhibited by inhibitor of CAD (ICAD). Activation of CAD needs the cleavage of
      ICAD by activated caspase-3. During the characterization of the staurosporine
      induced apoptotic process in human neuroblastoma cell lines, we have found three
      novel splice variants of CAD. In all three messengers, the open reading frame is
      truncated after the second exon of the CAD gene. This truncated open reading
      frame codifies the CAD protein amino terminal part corresponding to the cell
      death-inducing DFF45-like effector-N (CIDE-N) domain. We have detected these
      splicing variants in human tissues and in peripheral white blood cells from 10
      unrelated individuals, and their products have been showed to be expressed in
      certain mouse tissues. We demonstrate that these truncated forms of CAD are
      soluble proteins that interact with ICAD. We also provided evidences that these
      CIDE-N forms of CAD promote apoptosis in a caspase-dependent manner.

PMID- 15147902
TI  - ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and
      participates in apolipoprotein AI-dependent cholesterol export.
AB  - Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF-
      and ARL-family member whose mRNA-expression is induced by liver X
      receptor/retinoid X-receptor agonists or cholesterol loading in human
      macrophages. Moreover, subcellular distribution of mutant and wild type ARL7
      enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a
      vesicular transport step between a perinuclear compartment and the plasma
      membrane. Therefore, we investigated the effect of ARL7 over-expression on the
      cholesterol secretory pathway. We found that expression of wild type and dominant
      active ARL7-EGFP stimulated the rate of apolipoprotein AI-specific cholesterol
      efflux 1.7- and 2.8-fold. In contrast, expression of the dominant negative form
      of ARL7-EGFP led to approximately 50% inhibition of cholesterol efflux. This data
      is consistent with a model in which ARL7 is involved in transport between a
      perinuclear compartment and the plasma membrane apparently linked to the ABCA1
      mediated cholesterol secretion pathway.

PMID- 15147903
TI  - Glucocorticoid activation of the neuronal nicotinic acetylcholine receptor alpha7
      subunit gene: involvement of transcription factor Egr-1.
AB  - The alpha7 subunit is a component of nicotinic acetylcholine receptors expressed
      in bovine chromaffin cells. The peculiar localization of these receptors at
      adrenomedullary areas adjacent to the adrenal cortex suggests that factors,
      probably glucocorticoids, arising from the cortex might diffuse and regulate
      alpha7 receptor expression. In reporter gene transfection experiments,
      dexamethasone increased alpha7 promoter activity by up to fivefold in a
      concentration- and time-dependent manner despite the absence of consensus
      glucocorticoid receptor elements at the alpha7 promoter. Transcriptional
      activation induced by glucocorticoids was abolished through simultaneous mutation
      of at least two of the three sites for the immediate early transcription factor
      Egr-1, present in the proximal promoter region of the alpha7 subunit gene.
      Therefore, glucocorticoids activate the alpha7 subunit gene through Egr-1 in an
      indirect way.

PMID- 15147904
TI  - The N-terminal sequence directs import of mitochondrial alanine aminotransferase
      into mitochondria.
AB  - Herein, we report cloning and subcellular localization of two alanine
      aminotransferase (ALT) isozymes, cALT and mALT, from liver of gilthead sea bream
      (Sparus aurata). CHO cells transfected with constructs expressing cALT or mALT as
      C- or N-terminal fusion with the enhanced green fluorescent protein (EGFP) showed
      that cALT is cytosolic, whereas mALT localized to mitochondria. Fusion of EGFP to
      mALT N-terminus or removal of amino acids 1-83 of mALT avoided import into
      mitochondria, supporting evidence that the mALT N-terminus contains a
      mitochondrial targeting signal. The amino acid sequence of mALT is the first
      reported for a mitochondrial ALT in animals.

PMID- 15147905
TI  - Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after
      myocardial ischemia and reperfusion.
AB  - Big MAP kinase 1 (BMK1/ERK5) plays a critical role in pre-natal development of
      the cardiovascular system and post-natal eccentric hypertrophy of the heart. Of
      the two isoforms upstream of MAPK-kinase 5 (MEK5) known to exist, only the longer
      MEK5alpha isoform potently activates BMK1. We generated cardiac-specific
      constitutively active form of the MEK5alpha (CA-MEK5alpha transgenic (Tg) mice),
      and observed a 3 to 4-fold increase in endogenous BMK1 activation and
      hyperphosphorylation of connexin 43 in the ventricles of the Tg compared to wild
      type mice. The CA-MEK5alpha-Tg-mice demonstrated a profoundly accelerated
      recovery of left ventricular developed pressure after ischemia/reperfusion. We
      propose a novel role for BMK1 in protecting the heart from ischemia/reperfusion
      induced cardiac injury.

PMID- 15147906
TI  - Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation
      of tau and associated neurodegeneration.
AB  - Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, reduces the
      clinical deterioration in moderate-to-severe Alzheimer disease (AD) for which
      other treatments are not available. The activity of protein phosphatase (PP)-2A
      is compromised in AD brain and is believed to be a cause of the abnormal
      hyperphosphorylation of tau and the consequent neurofibrillary degeneration. Here
      we show that memantine inhibits and reverses the PP-2A inhibition-induced
      abnormal hyperphosphorylation and accumulation of tau in organotypic culture of
      rat hippocampal slices. Such restorative effects of memantine were not detected
      either with 5,7-dichlorokynurenic acid or with D(-)-2-amino-5-phosphopentanoic
      acid, NMDA receptor antagonists active at the glycine binding site and at the
      glutamate binding site, respectively. These findings show (1) that memantine
      inhibits and reverses the PP-2A inhibition-induced abnormal hyperphosphorylation
      of tau/neurofibrillary degeneration and (2) that this drug might be useful for
      the treatment of AD and related tauopathies.

PMID- 15147907
TI  - Monoglucosylated glycans in the secreted human complement component C3:
      implications for protein biosynthesis and structure.
AB  - The monoglucosylated oligomannose N-linked oligosaccharide
      (Glc(1)Man(9)GlcNAc(2)) is a retention signal for the calnexin-calreticulin
      quality control pathway in the endoplasmic reticulum. We report here the presence
      of such monoglucosylated N-glycans on the human complement serum glycoprotein C3.
      This finding represents the first report of monoglucosylated glycans on a human
      serum glycoprotein from non-diseased individuals. The presence of the glucose
      moiety in 5% of the human C3 glycoprotein suggests that this glycosylation site
      is sequestered within the protein and is consistent with previous studies
      identifying a cryptic conglutinin binding site on C3 that becomes exposed upon
      its conversion to iC3b.

PMID- 15147908
TI  - Cytoplasmic localization of calcium/calmodulin-dependent protein kinase I-alpha
      depends on a nuclear export signal in its regulatory domain.
AB  - Calcium/calmodulin-dependent protein kinase I-alpha (CaMKI-alpha) is a ubiquitous
      cytosolic enzyme that phosphorylates a number of nuclear proteins in vitro and
      has been implicated in transcriptional regulation. We report that cytoplasmic
      localization of CaMKI-alpha depends on CRM1-mediated nuclear export mediated
      through a Rev-like nuclear export signal in the CaMKI-alpha regulatory domain.
      Interaction of CaMKI-alpha with a CRM1 complex in vitro is enhanced by incubation
      with calcium/calmodulin. Translocation of CaMKI-alpha into the nucleus involves a
      conserved sequence located within the catalytic core. Mutation of this sequence
      partially blocks nuclear entry of an export-impaired mutant of CaMKI-alpha.

PMID- 15147909
TI  - Cytosol-derived proteins are sufficient for Arp2/3 recruitment and ARF/coatomer
      dependent actin polymerization on Golgi membranes.
AB  - The actin cytoskeleton has been implicated in protein trafficking at the Golgi
      apparatus and in Golgi orientation and morphology. Actin dynamics at the Golgi
      are regulated in part by recruiting Cdc42 or Rac to the membrane through a
      binding interaction with the coatomer-coated (COPI)-vesicle coat protein,
      coatomer. This leads to actin polymerization through the effector, N-WASP and the
      Arp2/3 complex. Here, we have used reconstitution of vesicle budding to test
      whether Arp2/3 is recruited to membranes during the formation of COPI vesicles.
      Our results revealed that ARF1 activation leads to greatly increased Arp3 levels
      on the membranes. Coatomer-bound Cdc42 and pre-existing F-actin are important for
      Arp2/3 binding. ARF1-dependent Arp2/3 recruitment and actin polymerization can be
      reconstituted on liposomal membranes, indicating that no membrane proteins are
      necessary. These results show that activated ARF1 can stimulate Arp2/3
      recruitment to Golgi membranes through coatomer, Cdc42 or Rac, and N-WASP.

PMID- 15147910
TI  - Activation of phospholipase D by osmotic cell swelling.
AB  - In response to osmotic cell swelling, Intestine 407 cells react with a rapid and
      transient activation of phospholipase D (PLD). To investigate the role of PLD
      during the regulatory volume decrease, cells were treated with 1-butanol
      resulting in a depletion of PLD substrates. Activation of volume-regulated anion
      channels, but not the cell swelling-induced release of taurine, was largely
      inhibited in the presence of low concentrations of 1-butanol. In addition,
      hypotonicity-induced exocytosis, ATP release and subsequent endocytosis were
      found to be largely abrogated. The results support a model of cell volume
      regulation in which PLD plays an essential role in the cell swelling-induced
      vesicle cycling and in the activation of volume-sensitive anion channels.

PMID- 15147911
TI  - Bioimaging TOF-SIMS: localization of cholesterol in rat kidney sections.
AB  - Here, we show the localization of a whole organic molecule in biological tissue
      using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Rat kidneys were
      sectioned by cryoultramicrotomy and dried at room temperature. The samples were
      covered with a thin silver layer and analyzed in an imaging TOF-SIMS instrument
      equipped with a Ga(+)-source. The cholesterol signal showed a high concentration
      in the nuclear areas of the epithelial cells and a lower concentration over areas
      representing the basal lamina of renal tubules. A more diffuse distribution of
      cholesterol was also found over areas representing the cytoplasm or plasma
      membrane of the epithelial cells.

PMID- 15147913
TI  - The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains
      more efficiently than its open-chain analogue.
AB  - The effects of a mammalian cyclic antimicrobial peptide, rhesus theta defensin 1
      (RTD-1) and its open chain analogue (oRTD-1), on the phase behaviour and
      structure of model membrane systems (dipalmitoyl phosphatidylcholine, DPPC and
      dipalmitoyl phosphatidylglycerol, DPPG) were studied. The increased selectivity
      of RTD-1 for anionic DPPG over zwitterionic DPPC was shown by differential
      scanning calorimetry. RTD-1, at a molar peptide-lipid ratio of 1:100, induced
      considerable changes in the phase behaviour of DPPG, but not of DPPC. The main
      transition temperature, Tm, was unchanged, but additional phase transitions
      appeared above Tm. oRTD-1 induced similar effects. However, the effects were not
      observable below a peptide:lipid molar ratio of 1:50, which correlates with the
      weaker biological activity of oRTD-1. Small- and wide-angle X-ray scattering
      revealed for DPPG the appearance of additional structural features induced by RTD
      1 above Tm, which were interpreted as correlated lamellar structures, with
      increased order of the fatty acyl side chains of the lipid. It is proposed that
      after initial electrostatic interaction of the cationic rim of the peptide with
      the anionic DPPG headgroups, leading to stabilized lipid-peptide clusters, the
      hydrophobic face of the peptide assists in its interaction with the fatty acyl
      side chains eventually leading to membrane disruption.

PMID- 15147912
TI  - Identification and characterization of a novel Rho GTPase activating protein
      implicated in receptor-mediated endocytosis.
AB  - Cbl-interacting protein of 85 kDa (CIN85) is a recently identified adaptor
      protein involved in the endocytic process of several receptor tyrosine kinases.
      Here we have identified a novel RhoGAP, CIN85 associated multi-domain containing
      Rho1 (CAMGAP1) as a binding protein for CIN85. CAMGAP1 is composed of an Src
      homology 3 (SH3) domain, multiple WW domains, a proline-rich region, a PH domain
      and a RhoGAP domain, and has the domain architecture similar to ARHGAP9 and
      ARHGAP12. CAMGAP1 mRNA is widely distributed in murine tissues. Biochemical
      assays showed its GAP activity toward Rac1 and Cdc42. Protein binding and
      expression studies indicated that the second SH3 domain of CIN85 binds to a
      proline-rich region of CAMGAP1. Overexpression of a truncated form of CAMGAP1
      interferes with the internalization of transferrin receptors, suggesting that
      CAMGAP1 may play a role in clathrin-mediated endocytosis.

PMID- 15147914
TI  - Cationic oligopeptide-mediated delivery of dsRNA for post-transcriptional gene
      silencing in plant cells.
AB  - We have used cationic oligopeptide polyarginine-12mer (POA) to deliver double
      stranded RNA (dsRNA), prepared in vitro, to tobacco (Nicotiana tabacum)
      suspension cells. POA interacts electrostatically with dsRNA to form a complex.
      When dsRNA for the GUS or NPTII gene was delivered into cells carrying the same
      genes, the corresponding mRNA was degraded. Using RNase protection assay we were
      able to detect 21-bp small interfering RNA in dsRNA/POA-treated cells. These
      results demonstrate that POA can be used to deliver dsRNA to induce post
      transcriptional gene silencing in plant cells.

PMID- 15147916
TI  - Manganese levels during pregnancy and at birth: relation to environmental factors
      and smoking in a Southwest Quebec population.
AB  - Manganese (Mn) is both an essential element and a potent neurotoxin. Higher
      demand during pregnancy leads to increased blood levels. Previous studies have
      suggested that environmental factors may influence blood Mn levels. As part of a
      community-based survey of potentially toxic environmental contaminants among
      pregnant women, the objective of this exploratory study was to examine the Mn
      status in pregnant women and their newborns with respect to sociodemographic and
      environmental variables. Pregnant women from Southwest Quebec were recruited in
      the first or second trimester through the public health prenatal program Mn was
      analyzed in mother's blood at entry into the study, in the second trimester (for
      those who entered during the first trimester), and at delivery, as well as in
      umbilical cord blood and in placental tissue. Sociodemographic data and
      information about pregnancy were obtained by two questionnaires; the first was
      administered at study entry and the second a few weeks following birth. Results
      showed that mothers' Mn blood levels increased significantly during pregnancy and
      cord blood Mn levels were significantly higher than those for mothers' blood.
      There was no relation to age. Smokers had significantly lower Mn blood levels
      compared to nonsmokers at the second trimester. Those who lived in urban and/or
      agricultural areas had significantly higher levels compared to those who lived in
      small villages. Those who reported pesticide spraying less than 1 km from their
      house likewise had significantly higher levels compared to the others. These
      findings suggest that lifestyle and environmental factors may interfere with the
      delicate balance and homeostatic mechanisms required to maintain Mn at optimal
      levels for physiological changes during pregnancy.

PMID- 15147915
TI  - Replacement of domain b of human protein disulfide isomerase-related protein with
      domain b' of human protein disulfide isomerase dramatically increases its
      chaperone activity.
AB  - We have reported that human protein disulfide isomerase-related protein (hPDIR)
      has isomerase and chaperone activities that are lower than those of the human
      protein disulfide isomerase (hPDI), and that the b domain of hPDIR is critical
      for its chaperone activity [J. Biol. Chem. 279 (2004) 4604]. To investigate the
      basis of the differences between hPDI and hPDIR, and to determine the functions
      of each hPDIR domain in detail, we constructed several hPDIR domain mutants.
      Interestingly, when the b domain of hPDIR was replaced with the b' domain of
      hPDI, a dramatic increase in chaperone activity that was close to that of hPDI
      itself was observed. However, this mutant showed decreased oxidative refolding of
      alpha1-antitrypsin. The replacement of the b domain of hPDIR with the c domain of
      hPDI also increased its chaperone activity. These observations suggest that
      putative peptide-binding sites of hPDI determine both its chaperone activity and
      its substrate specificity.

PMID- 15147917
TI  - Psychophysical sensory examination in individuals with a history of methylmercury
      exposure.
AB  - Paresthesias are the first symptom that people report following toxic doses of
      methylmercury. The authors conducted a psychophysical study of tactile sensation
      to evaluate the somatosensory abilities of subjects living in a methylmercury
      polluted area around Minamata City, Japan. The authors examined control subjects
      and methylmercury-exposed subjects with and without numbness. A history of
      methylmercury exposure was taken and a neurological examination performed.
      Aluminum-oxide abrasive papers were used as stimuli in a psychophysical sensory
      examination of fine-surface-texture discrimination. Difference thresholds from 3
      microm were calculated by the two-alternative, forced-choice technique.
      Difference thresholds in control subjects were also calculated for comparison.
      The difference threshold was 6.3 microm in exposed subjects with sensory
      symptoms, 4.9 microm in exposed subjects without sensory symptoms, and 2.7 microm
      in control subjects. Acuity of fine-surface-texture discrimination was disturbed
      not only in subjects with clinical complaints of hand numbness, but also in
      subjects without hand numbness who lived in the district where methylmercury
      exposure occurred. Sensory testing using a psychophysical test of fine-surface
      texture discrimination in this population suggests that the number of individuals
      affected by methylmercury exposure in the polluted area was greater than
      previously reported.

PMID- 15147918
TI  - Assessment of lead exposure and associated risk factors in urban children in
      Silesia, Poland.
AB  - A program of childhood lead poisoning prevention was conducted in six cities of
      Silesia, the most industrialized region of Poland. We analyzed records of 11,877
      children aged 24-84 months, tested between 1993 and 1998, to assess children's
      exposure to lead and associations of blood lead levels (BLL) with season of
      sampling, questionnaire data, and environmental levels of lead. Air lead
      concentrations and lead fallout, as measured in the ambient air monitoring
      system, were below current Polish air quality standards and gradually decreased.
      The geometric mean (GM) BLL was 6.3 microg/dL (range from 0.6 to 48 microg/dL),
      and >13% of children had BLL > or =10 microg/dL. Mean BLL declined from 6.8
      microg/dL in 1993-1994 to almost 5.5 microg/dL in 1998. GM BLL in spring and
      summer ('nonheating' season) months were 10% higher than BLL in children tested
      in fall and winter ('heating' season), although air lead concentrations were
      lower in nonheating and higher in the heating season. For both the heating and
      nonheating seasons, there was a significant increase in the mean BLL with
      increasing air lead concentrations. Poor housing (odds ratio (OR): 1.82; 95% CI:
      1.4, 2.3), two or more siblings in the family (OR: 3.12; 95% CI: 2.6, 3.7), lack
      of recreational trips outside the region (OR: 1.66; 95% CI: 1.47, 1.89), and the
      time child spent outdoors were associated with elevated BLL. Variables found to
      affect BLL in the Silesian children should be used to propose criteria to improve
      identification of children at risk and to focus prevention activities more
      effectively.

PMID- 15147920
TI  - Effects of Asian dust storm events on daily mortality in Taipei, Taiwan.
AB  - In spring, windblown dust storms originating in the deserts of Mongolia and China
      make their way to Taipei City. These occurrences are known as Asian dust storm
      events. The objective of this study was to assess the possible effects of Asian
      dust storms on the mortality of residents in Taipei, Taiwan, during the period
      from 1995 to 2000. We identified 39 dust storm episodes, which were classified as
      index days. Daily deaths on the index days were compared with deaths on the
      comparison days. We selected two comparison days for each index day, 7 days
      before the index day and 7 days after the index day. The strongest estimated
      effects of dust storms were increases of 7.66% in risk for respiratory disease 1
      day after the event, 4.92% for total deaths 2 days following the dust storms and
      2.59% for circulatory diseases 2 days following the dust storms. However, none of
      these effects were statistically significant. This study found greater
      specificity for associations with respiratory deaths, and this increases the
      likelihood that the association between dust events and daily mortality
      represents a causal relationship.

PMID- 15147919
TI  - The effects of environmental cadmium exposure on kidney function: the possible
      influence of age.
AB  - The study aimed to assess the possible influence of long-term environmental
      exposure to cadmium and age at the time of exposure on renal function. The study
      was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium
      contaminated area in the vicinity of a zinc smelter. Since the smelter was built
      in the late 1950s but was not operated until 1968, some of the inhabitants were
      not exposed to cadmium during childhood. For the follow-up, 308 persons who in
      1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity
      (1.020) were selected in 2000. The study population included 136 people who were
      exposed to cadmium in childhood (former children) and 172 adults (unexposed
      adults) with no such exposure. These two groups were divided into subgroups
      according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g
      creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular
      dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb
      U and beta2 M-S) were measured. Persons with a history of occupational exposure
      to cadmium were excluded from this project. In group 3 of the unexposed adults,
      concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than
      those in group 1. In former children, this could be observed only for RPB-U and
      Alb-U. Urine concentrations of these markers were higher in all of the subgroups
      of former children than in the groups of unexposed adults (except for NAG and its
      two forms). However, these differences were significant only for RBP-U in group
      3. The findings indicate that early renal effects in the general population may
      occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for
      NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the
      renal function, particularly tubular reabsorption, than the exposure of a mature
      organism.

PMID- 15147921
TI  - Methods and issues in conducting a community-based environmental randomized
      trial.
AB  - The environment is suspected to play an important role in the prevalence and
      severity of asthma in inner-city children. This paper describes the
      implementation and baseline data of an inner-city community-based participatory
      research clinical trial designed to test the effectiveness of a pollutant and
      allergen control strategy on children's asthma morbidity. Participants were 100
      elementary-school-aged children with asthma, graduates of a school-based asthma
      education program in East Baltimore. The intervention for half of the randomly
      assigned families consisted of environmental control education, allergen-proof
      encasements, pest extermination, and a HEPA air cleaner at the beginning of the
      study. Controls received the same at the end of the study. Participants visited a
      clinic for questionnaires, allergy skin testing, spirometry, and blood sample at
      baseline and 12 months. Home environments, NO(2), O(3), airborne particulates,
      and allergens were evaluated at baseline and at 6 and 12 months. Asthma morbidity
      and adherence was assessed quarterly. Collaboration with the community proved
      very beneficial in creating a study design and procedures acceptable to an inner
      city community.

PMID- 15147922
TI  - Effects of mercury and selenite on delta-aminolevulinate dehydratase activity and
      on selected oxidative stress parameters in rats.
AB  - The present study evaluates the effects of Na(2)SeO(3) and HgCl(2) on kidney and
      liver of adult rats. In vivo, HgCl(2) (17 micromol/kg, sc) reduced ascorbic acid
      levels in liver ( approximately 15%), whereas in kidney it reduced ALA-D activity
      ( approximately 60%) and ascorbic acid levels ( approximately 35%) and increased
      TBARS content ( approximately 50%). Na(2)SeO(3) (17 micromol/kg, sc) exposure
      increased the content of nonprotein thiol groups in liver (35-60%) and kidney (
      approximately 50-160%), partially prevented mercury-induced ALA-D inhibition in
      kidney, and completely prevented a mercury-induced increase of TBARS content and
      decrease of ascorbic acid levels in kidney. In vitro, HgCl(2) and Na(2)SeO(3)
      inhibited renal and hepatic ALA-D, while HgCl(2) increased TBARS in renal and
      hepatic tissue preparations. Na(2)SeO(3) increased the rate of glutathione
      oxidation in vitro. Results indicated that Na(2)SeO(3) protected against HgCl(2)
      effects in vivo (prevention of mercury interaction with thiol groups and of
      mercury-induced oxidative damage). In vitro, Na(2)SeO(3) did not prevent mercury
      effects, but potentiated ALA-D inhibition by mercury, probably due to its ability
      to oxidize thiol groups.

PMID- 15147923
TI  - Perceptions of general environmental problems, willingness to expend federal
      funds on these problems, and concerns regarding the Los Alamos National
      Laboratory: Hispanics are more concerned than Whites.
AB  - Perceptions about general environmental problems, governmental spending for these
      problems, and major concerns about the US Department of Energy's Los Alamos
      National Laboratory (LANL) were examined by interviewing 356 people attending a
      gun show in Albuquerque, New Mexico. The hypothesis that there are differences in
      these three areas as a function of ethnicity was examined. We predicted that if
      differences existed, they would exist for all three evaluations (general
      environmental problems, government spending, and environmental concerns about
      LANL). However, this was not the case; there were fewer ethnic differences
      concerning LANL. Hispanics rated most general environmental problems higher than
      Whites and rated their willingness to expend federal funds higher than Whites,
      although all groups gave a lower score on willingness than on concern. Further,
      the congruence between these two types of ratings was higher for Hispanics than
      for others. In general, the concerns expressed by subjects about LANL showed few
      ethnic differences, and everyone was most concerned about contamination. These
      data indicate that Hispanics attending a gun show are equally or more concerned
      than others about environmental problems generally but are not more concerned
      about LANL. The data can be useful for developing future research and stewardship
      plans and for understanding general environmental problems and their relationship
      to concerns about LANL. More generally, they indicate that the attitudes and
      perceptions of Hispanics deserve increased study in a general population.

PMID- 15147924
TI  - Polycyclic aromatic hydrocarbons and polychlorobiphenyls in wastewaters and
      sewage sludges from the Paris area (France).
AB  - Polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs) were
      investigated during 1999-2000 in the sewerage system to the Seine Aval treatment
      plant which drains the Paris area (France). Contamination of sludges from storage
      chambers indicated a local origin typical of motor car traffic with PAH
      concentrations (Sigma16) ranging from 14 to 31 mg kg(-1) of dry weight,
      pyrene/fluoranthene ratios ranging between 1.12 and 1.48 and PCB concentrations
      (Sigma7) ranging from 0.07 to 0.65 mg kg(-1) of dry weight. In the same way,
      sludges from sand removal tanks displayed PAH values related to the importance of
      traffic whereas PCBs were rather characteristic of a diffuse origin. Among the
      five sewers entering the Seine Aval treatment plant, Clichy Argenteuil, which
      drains a large industrial area, was the most polluted one (PAHs as Sigma3, 10 kg
      year(-1); PCBs as Sigma7, 3.5 kg year(-1)). Seasonal variations were observed for
      PAHs with higher levels in winter in relation with the occurrence of combustion
      processes. Ninety-eight percent of the PAHs and 76% of the PCBs were extracted
      during the treatment plant processes, the primary clarifier of which retained 50%
      of the pollutants. Fluoranthene and PCB concentrations in the final dehydrated
      sludge (mean values) were 1.07 and 0.623 mg kg(-1) of dry weight, respectively.
      For PCBs, a significant correlation was found (r=0.668, P<0.001) between
      wastewater and dehydrated sludge concentrations. Yearly measured amounts of PAHs
      (Sigma3) were twice higher in sludges (76.3 kg) than in precipitations (37.7 kg)
      whereas those of PCBs (Sigma7) brought by total atmospheric fallout (17.6 kg) and
      sludges (21.1 kg) did not differ significantly.

PMID- 15147925
TI  - Pollutants emitted by a cement plant: health risks for the population living in
      the neighborhood.
AB  - The aim of this study was to investigate the health risks due to combustor
      emissions in the manufacturing of Portland cement for the population living in
      the neighborhood of a cement kiln in Catalonia, Spain. Pollutants emitted to the
      atmosphere in the course of cement production were modeled. The ISC3-ST model was
      applied to estimate air dispersion of the contaminants emitted by the cement
      plant. Air concentrations of NO(2), SO(2), PM(10), metals, and polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), as well as the potential exposure
      in the vicinity of the facility, were assessed via models based on US EPA
      guidance documents. PCDD/F and metal concentrations were also modeled for soil
      and vegetation. Based on these concentrations, the levels of human exposure were
      calculated. Individual cancer and noncancer risks for the emissions of the cement
      kiln were assessed. Health effects due to NO(2), SO(2), and PM(10) emissions were
      also evaluated. Risk assessment was performed as a deterministic analysis. The
      main individual risk in the population was evaluated in a central-tendency and a
      high-end approach. The results show that the incremental individual risk due to
      emissions of the cement plant is very low not only with regard to health effects,
      but also in relation to toxicological and cancer risks produced by pollutants
      such as metals and PCDD/Fs emitted by the cement kiln.

PMID- 15147926
TI  - Estimating the mercury exposure dose in a population of migratory bird hunters in
      the St. Lawrence River region, Quebec, Canada.
AB  - St. Lawrence River hunters (Quebec, Canada) are exposed to the pollutants,
      especially mercury, that contaminate birds and fish. However, the health risks of
      this have remained unclear because of a lack of information about the hunters'
      duck, geese, and sportfish consumption habits. A nutritional survey was set up to
      characterize waterfowl and sportfish consumption in St. Lawrence River duck
      hunters and to estimate their daily exposure to mercury. During the winter of
      2000, 512 hunters selected from the Canadian Wildlife Service database completed
      a self-administered questionnaire. Daily exposure to contaminants was measured
      using data from the Canadian Wildlife Service (waterfowl) and available data on
      St. Lawrence River sportfish. The annual average consumption was 7.5 meals of
      ducks and geese and 8.7 meals of sportfish. The daily exposure to mercury related
      to waterfowl consumption was below the Canadian tolerable daily intake (TDI) of
      0.47 microg/kg body wt/day for all participants. The daily mercury intake
      associated with fish consumption was greater than the TDI in 2 duck hunters. The
      daily exposure to mercury was higher than the TDI in 4 participants when both
      waterfowl and fish consumption were combined. Our results suggest that fish
      consumption (especially freshwater fish) represents the main source of exposure
      to pollutants in duck hunters.

PMID- 15147927
TI  - Recreational rates and future land-use preferences for four Department of Energy
      sites: consistency despite demographic and geographical differences.
AB  - The management of ecosystems has been improved by both a public understanding of
      ecosystem structure and function and by managers' understanding of public
      perceptions and attitudes. This is especially true for contaminated lands where
      there are a variety of remediation, restoration, and future land-use decisions to
      be made. This paper synthesizes several surveys from four US Department of Energy
      (DOE) sites in the states of South Carolina, Idaho, Nevada, and New York.
      Although ethnic composition varied among the sites, age and gender did not. The
      percentage of the study population engaged in hunting ranged from 30% to 41% and
      that in fishing ranged from 55% to 74%. Average hunting rates ranged from 9 (New
      York) to 15 (South Carolina) days/year; average fishing rates ranged from 12 (New
      Mexico) to 38 (New York) days a year. Despite the demographic and recreational
      rate differences, there was remarkable agreement about future land uses.
      Maintaining these DOE sites as National Environmental Research Parks and using
      them for nonconsumptive recreation rated the highest. The lowest rated future
      land uses were current and additional nuclear waste storage and the building of
      homes and factories. People who participated in a recreational activity rated
      those future land uses higher than nonusers. While these data on recreational
      rates can be used to assess the potential risk to people using contaminated sites
      and to aid in setting clean-up standards based on potential risk, the information
      on land-use preferences can be used by managers to determine future use and to
      plan for such use. This information is particularly relevant to the Department of
      Energy's "Risk-based End State Vision."

PMID- 15147928
TI  - Metabolical effects of Folidol 600 on the neotropical freshwater fish matrinxa,
      Brycon cephalus.
AB  - The neotropical freshwater fish matrinxa, Brycon cephalus (Gunther, 1869), was
      exposed to 1/3 of 96 h-LC50 of Folidol 600 (methyl parathion) for 96 h and
      allowed to recover for 24, 48, 96, and 192 h. Acetylcholinesterase (AChE),
      alanine aminotransferase (ALAT), aspartate aminotransferase (AAT), lactate
      dehydrogenase (LDH), malate dehydrogenase (MDH), and glutamate dehydrogenase
      (GDH) were assayed in brain, liver, muscle, and plasma. Plasma and brain AChE
      activities were strongly inhibited (64% and 87%, respectively), remaining low in
      the brain during recovery. Liver ALAT decreased 59.4% and plasma ALAT increased
      94.2%. This response, associated with GDH reduction during the recovery period,
      was attributed to impairment of amino acid metabolism and to liver damage. The
      increase of heart and plasma AAT suggested tissue injury. Liver and plasma LDH
      and MDH did not change during the exposure to Folidol, but liver MDH decreased
      34% during recovery, indicating a failure of oxidative metabolism in such tissue.
      Hepatic glycogen and glucose levels decreased 80.4 and 55%, respectively,
      followed by glucose mobilization to the plasma. The hepatic and muscular profile
      of lactate after recovery suggested gluconeogenesis without tissue hypoxia. These
      results revealed that methyl parathion affects the intermediary metabolism of
      matrinxa and that the assayed enzymes can work as good biomarkers of
      organophosphorus pesticide contamination.

PMID- 15147929
TI  - Microbial quality of tilapia reared in fecal-contaminated ponds.
AB  - The microbial quality of tilapia reared in four fecal-contaminated fishponds was
      investigated. One of the fishponds (TDP) received treated sewage with an average
      fecal coliform count of 4 x 10(3)cfu/100mL, and feed of fresh duckweed grown on
      treated sewage was used. The number of fecal coliform bacteria attached to
      duckweed biomass ranged between 4.1 x 10(2) and 1.6 x 10(4)cfu/g fresh weight.
      The second fishpond (TWP) received treated sewage, and the feed used was wheat
      bran. The third fishpond (FDP) received freshwater, and the feed used was the
      same duckweed. Pond 4 (SSP) received only settled sewage with an average fecal
      coliform count of 2.1 x 10(8)/100mL. The average counts in the fishponds were 2.2
      x 10(3), 1.7 x 10(3), 1.7 x 10(2), and 9.4 x 10(3)cfu/100mL in TDP, TWP, FDP, and
      SSP, respectively. FDP had a significantly (P < 0.05) lower fecal coliform count
      than the treated sewage-fed ponds and SSP. The microbial quality of the tilapia
      indicated that all tissue samples except muscle tissues were contaminated with
      fecal coliform. Ranking of the fecal coliform contamination levels showed a
      decrease in the order intestine>gills>skin>liver. Poor water quality (ammonia and
      nitrite) in SSP resulted in statistically higher fecal coliform numbers in fish
      organs of about 1 log(10) than in treatments with good water quality.
      Pretreatment of sewage is therefore recommended.

PMID- 15147930
TI  - Spatial categories and the estimation of location.
AB  - Four experiments are reported in which people organize a space hierarchically
      when they estimate particular locations in that space. Earlier work showed that
      people subdivide circles into quadrants bounded at the vertical and horizontal
      axes, biasing their estimates towards prototypical diagonal locations within
      those spatial categories (Psychological Review 98 (1991) 352). In this work
      Huttenlocher, Hedges, and Duncan showed that the use of such spatial categories
      can increase the accuracy of estimation of inexactly represented locations. The
      stimulus locations we examined were uniformly distributed across the circle. In
      the present study we explore whether variation in the distribution of locations
      affects how the circle is categorized. Other things being equal, categories that
      capture high density regions in a stimulus space should contribute most to
      accuracy of estimation. However, precision of boundaries is also important to
      accuracy; with imprecise boundaries stimuli may be misclassified, leading to
      large errors in estimation. We found that people use the same spatial categories
      regardless of the distribution of the locations. We argue that this spatial
      organization nevertheless can maximize the accuracy of estimates because vertical
      and horizontal category boundaries are the most exact, minimizing
      misclassification of stimuli.

PMID- 15147931
TI  - Developmental dyscalculia and basic numerical capacities: a study of 8-9-year-old
      students.
AB  - Thirty-one 8- and 9-year-old children selected for dyscalculia, reading
      difficulties or both, were compared to controls on a range of basic number
      processing tasks. Children with dyscalculia only had impaired performance on the
      tasks despite high-average performance on tests of IQ, vocabulary and working
      memory tasks. Children with reading disability were mildly impaired only on tasks
      that involved articulation, while children with both disorders showed a pattern
      of numerical disability similar to that of the dyscalculic group, with no special
      features consequent on their reading or language deficits. We conclude that
      dyscalculia is the result of specific disabilities in basic numerical processing,
      rather than the consequence of deficits in other cognitive abilities.

PMID- 15147932
TI  - An L1-script-transfer-effect fallacy: a rejoinder to Wang et al. (2003).
AB  - Do different L1 (first language) writing systems differentially affect word
      identification in English as a second language (ESL)? Wang, Koda, and Perfetti
      [Cognition 87 (2003) 129] answered yes by examining Chinese students with a
      logographic L1 background and Korean students with an alphabetic L1 background
      for their phonological and orthographic processing skills on English word
      identification. Such a conclusion is premature, however. We propose that the L1
      phonological system (rather than the L1 writing system) of the learner largely
      accounts for cognitive processes in learning to read a second language (L2).

PMID- 15147934
TI  - Syntax or semantics? Response to Lidz et al.

PMID- 15147935
TI  - Learning antecedents for anaphoric one.
AB  - Lidz et al. [Lidz, J., Waxman, S., & Freedman, J. (2003). What infants know about
      syntax but couldn't have learned: Experimental evidence for syntactic structure
      at 18 months. Cognition, 89, B65-B73.] claim experimental substantiation of an
      argument from the poverty of the stimulus, in the sense of Pullum and Scholz
      [Linguist. Rev. 19 (2002) 9]. They cite a specific feature of English--the
      assignment of appropriate antecedents for anaphoric one--that cannot possibly be
      learned from experience because the evidence needed is found only in utterances
      of a type too rare to be encountered. Their argument involves three empirical
      claims. In this note we dispute all three.

PMID- 15147936
TI  - Learning the unlearnable: the role of missing evidence.
AB  - Syntactic knowledge is widely held to be partially innate, rather than learned.
      In a classic example, it is sometimes argued that children know the proper use of
      anaphoric one, although that knowledge could not have been learned from
      experience. Lidz et al. [Lidz, J., Waxman, S., & Freedman, J. (2003). What
      infants know about syntax but couldn't have learned: Experimental evidence for
      syntactic structure at 18 months. Cognition, 89, B65-B73.] pursue this argument,
      and present corpus and experimental evidence that appears to support it; they
      conclude that specific aspects of this knowledge must be innate. We demonstrate,
      contra Lidz et al., that this knowledge may in fact be acquired from the input,
      through a simple Bayesian learning procedure. The learning procedure succeeds
      because it is sensitive to the absence of particular input patterns--an aspect of
      learning that is apparently overlooked by Lidz et al. More generally, we suggest
      that a prominent form of the "argument from poverty of the stimulus" suffers from
      the same oversight, and is as a result logically unsound.

PMID- 15147938
TI  - Mental representations of social status.
AB  - How do people think about social status? We investigated the nature of social
      status and number representations using a semantic distance latency test. In
      Study 1, 21 college students compared words connoting different social status as
      well as numbers, which served as a control task. Participants were faster at
      comparing occupations and numbers that were semantically farther apart relative
      to those more closely related. In Study 2, we examined the semantic distance
      effect for a social status category, for which participants have as much
      knowledge of, as with numbers. We asked 15 US Navy Midshipmen to compare the
      social status associated with different ranks in the Navy as well as compare
      number magnitudes. Participants were fastest when comparing ranks far in status
      relative to ranks close in status. These findings reveal that humans have mental
      representations of social status that share properties with that of number.

PMID- 15147939
TI  - Number bias for the discrimination of large visual sets in infancy.
AB  - This brief report attempts to resolve the claim that infants preferentially
      attend to continuous variables over number [e.g. Psychol. Sci. 10 (1999) 408;
      Cognit. Psychol.44 (2002) 33] with the finding that when continuous variables are
      controlled, infants as young as 6-months of age discriminate large numerical
      values [e.g. Psychol. Sci. 14 (2003) 396; Cognition 89 (2003) B15; Cognition 74
      (2000) B1]. In two parallel experiments, we compare 6-month-old infants' ability
      to discriminate number and ignore continuous variables with their ability to form
      a representation of a cumulative surface area and ignore number. We find that
      infants discriminate a 2-fold change in number but fail to discriminate a 2-fold
      change in cumulative surface area. The results point to a more complicated
      relationship between discrete and continuous dimensions than implied by previous
      literature.

PMID- 15147940
TI  - Seeing to hear better: evidence for early audio-visual interactions in speech
      identification.
AB  - Lip reading is the ability to partially understand speech by looking at the
      speaker's lips. It improves the intelligibility of speech in noise when audio
      visual perception is compared with audio-only perception. A recent set of
      experiments showed that seeing the speaker's lips also enhances sensitivity to
      acoustic information, decreasing the auditory detection threshold of speech
      embedded in noise [J. Acoust. Soc. Am. 109 (2001) 2272; J. Acoust. Soc. Am. 108
      (2000) 1197]. However, detection is different from comprehension, and it remains
      to be seen whether improved sensitivity also results in an intelligibility gain
      in audio-visual speech perception. In this work, we use an original paradigm to
      show that seeing the speaker's lips enables the listener to hear better and hence
      to understand better. The audio-visual stimuli used here could not be
      differentiated by lip reading per se since they contained exactly the same lip
      gesture matched with different compatible speech sounds. Nevertheless, the noise
      masked stimuli were more intelligible in the audio-visual condition than in the
      audio-only condition due to the contribution of visual information to the
      extraction of acoustic cues. Replacing the lip gesture by a non-speech visual
      input with exactly the same time course, providing the same temporal cues for
      extraction, removed the intelligibility benefit. This early contribution to audio
      visual speech identification is discussed in relationships with recent
      neurophysiological data on audio-visual perception.

PMID- 15147941
TI  - Language-mediated eye movements in the absence of a visual world: the 'blank
      screen paradigm'.
AB  - The 'visual world paradigm' typically involves presenting participants with a
      visual scene and recording eye movements as they either hear an instruction to
      manipulate objects in the scene or as they listen to a description of what may
      happen to those objects. In this study, participants heard each target sentence
      only after the corresponding visual scene had been displayed and then removed.
      For a scene depicting a man, a woman, a cake, and a newspaper, the eyes were
      subsequently directed, during 'eat' in 'the man will eat the cake', towards where
      the cake had previously been located even though the screen had been blank for
      over 2 s. The rapidity of these movements mirrored the anticipatory eye movements
      observed in previous studies [Cognition 73 (1999) 247; J. Mem. Lang. 49 (2003)
      133]. Thus, anticipatory eye movements are not dependent on a concurrent visual
      scene, but are dependent on a mental record of the scene that is independent of
      whether the visual scene is still present.

PMID- 15147942
TI  - Identification and characterization of a novel component of the cornified
      envelope, cornifelin.
AB  - Psoriasis is recognized as a chronic inflammatory disease characterized by
      epidermal hyperproliferation. To identify psoriasis-related genes, we compared
      the mRNA populations of normal and psoriatic skin. We identified one gene,
      designated as cornifelin, which showed increased expression in psoriatic skin.
      Human cornifelin contains 112 amino acids and is expressed in the uterus, cervix,
      and skin. In situ hybridization analysis demonstrated the presence of human
      cornifelin in the granular cell layer of the epidermis. To investigate the
      function of cornifelin, we established a transgenic mouse line overexpressing
      human cornifelin. Using these mice, we have shown that cornifelin is directly or
      indirectly cross-linked to at least two other cornified envelope proteins,
      loricrin and involucrin, in vivo. Overexpression of human cornifelin correlated
      with decreased loricrin expression and increased involucrin expression in the
      transgenic mouse. However, abnormality of epidermal differentiation was not
      observed in the transgenic mouse.

PMID- 15147943
TI  - Identification of insulin-responsive regions in the HMG-CoA reductase promoter.
AB  - An insulin-responsive line of rat hepatoma cells, H4IIE, was used to investigate
      the basis for insulin's transcriptional regulation of HMG-CoA reductase. Insulin
      addition to the media of these cells resulted in at least a 10-fold increase in
      levels of HMG-CoA reductase protein. Adding insulin to H4IIE cells transfected
      with pHMGR1 (containing the proximal reductase promoter from -270 to +20 ligated
      to luciferase) caused greater than 10-fold increases in luciferase activity.
      Transfections carried out with a series of deletion constructs identified insulin
      responsive regions between -203 and -130 (contains the SRE sequence) and between 
      85 and -105 (contains a CRE sequence). Mutation of the SRE in the -203 to -130
      sequence did not decrease activation by insulin. In contrast, mutation of the C
      at -90 of the CRE completely eliminated the insulin response. The data suggest
      that insulin's activation of HMG-CoA reductase involves the CRE in the -85 to 
      105 region and the -203 to -130 region of the promoter exclusive of the SRE.

PMID- 15147944
TI  - Expression of connective tissue growth factor, a biomarker in senescence of human
      diploid fibroblasts, is up-regulated by a transforming growth factor-beta
      mediated signaling pathway.
AB  - Molecular changes associated with cellular senescence in human diploid
      fibroblasts (HDF), IMR-90, were analyzed by two-dimensional differential proteome
      analysis. A high percentage of replicative senescent cells were positive for
      senescence-associated beta-galactosidase activity, and displayed elevated levels
      of p21 and p53 proteins. Comparison of early population doubling level (PDL)
      versus replicative senescent cells among the 1000 spots resolved on gels revealed
      that the signal intensities of six spots were increased fivefold, whereas those
      of four spots were decreased. Proteome analysis data demonstrated that connective
      tissue growth factor (CTGF) is an age-associated protein. Up-regulation of CTGF
      expression in senescent cells was further confirmed by Western blotting and RT
      PCR. We postulate that CTGF expression is controlled, in part, by transforming
      growth factor-beta (TGF-beta), in view of the high levels of TGF-beta isoforms as
      well as type I and II receptors detected only in late PDL of HDF cells. To verify
      this hypothesis, we stimulated early PDL cells with TGF-beta1 as well as stress
      inducing agents such as hydrogen peroxide. As expected, CTGF expression and Smad
      protein phosphorylation were dramatically increased up to observed levels in
      normal replicative senescent cells. In vivo experiments disclosed that CTGF,
      pSmad, and p53 were constitutively expressed at basal levels in up to 18-month
      old rat liver, and expression was significantly up-regulated in 24-month-old rat
      tissue. However, expression patterns were not altered at all periods examined in
      livers of caloric-restricted rats. In view of both in vitro and in vivo data, we
      propose that the TGF-beta/Smad pathway functions in the induction of CTGF, a
      novel biomarker protein of cellular senescence in human fibroblasts.

PMID- 15147945
TI  - Insulin reduces the requirement for EGFR transactivation in bombesin-induced DNA
      synthesis.
AB  - The binding of bombesin to its cognate G-protein coupled receptor stimulates
      quiescent Swiss 3T3 cells to re-initiate DNA synthesis and cell division.
      Addition of a non-mitogenic concentration of insulin dramatically potentiates
      bombesin-induced cell proliferation. We examined whether bombesin-induced EGFR
      transactivation mediates synergistic cell proliferation induced by bombesin and
      insulin. Treatment with selective EGFR tyrosine kinase inhibitors blocked EGFR
      transactivation, DNA synthesis, the transition of cells from quiescence into the
      cell cycle, and the expression of cyclins D1 and E induced by bombesin alone. In
      contrast, the inhibitors prevented cell cycle progression to a much lesser degree
      in cells stimulated with the combination of bombesin and insulin. Our results
      indicate that EGFR transactivation does not mediate synergistic cell
      proliferation induced by bombesin and insulin, and imply that insulin compensates
      for the requirement for EGFR transactivation in bombesin-induced DNA synthesis.

PMID- 15147947
TI  - Phosphatidic acid positively regulates LPS-induced differentiation of RAW264.7
      murine macrophage cell line into dendritic-like cells.
AB  - Phosphatidic acid (PA) is an important second messenger produced by the
      activation of numerous cell surface receptors. Recent data have suggested that PA
      regulates multiple cellular processes. In this study, we found that PA positively
      regulates the lipopolysaccharide (LPS)-induced differentiation of RAW264.7 murine
      macrophage cells into dendritic-like cells. Co-treatment of PA with LPS further
      increased dendritic cell surface marker expressions (CD80, CD86, CD40, MHC class
      I, and class II antigens) and reduced the phagocytic activity of LPS-treated
      cells. Moreover, PA up regulated allostimulatory activity and the secretion of IL
      12 in LPS-treated RAW264.7 cells. Taken together, these data indicate that PA
      might play a role in the LPS-mediated differentiation of macrophage cells into
      dendritic-like cells.

PMID- 15147946
TI  - Assembly of human severe acute respiratory syndrome coronavirus-like particles.
AB  - Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV)
      consist of three virion structural proteins, including spike protein, membrane
      protein, and envelope protein. In this report, virus-like particles were
      assembled in insect cells by the co-infection with recombinant baculoviruses,
      which separately express one of these three virion proteins. We found that the
      membrane and envelope proteins are sufficient for the efficient formation of
      virus-like particles and could be visualized by electron microscopy. Sucrose
      gradient purification followed by Western blot analysis and immunogold labeling
      showed that the spike protein could be incorporated into the virus like particle
      also. The construction of engineered virus-like particles bearing resemblance to
      the authentic one is an important step towards the development of an effective
      vaccine against infection of SARS CoV.

PMID- 15147948
TI  - Adaptation of ghrelin levels to limit body weight gain in the obese Zucker rat.
AB  - In this study, we measured the ghrelin, leptin, and insulin variations in lean
      and obese Zucker fa/fa rats during the acute phase of body weight gain. At 2
      months of age, plasma insulin and leptin concentrations in fa/fa rats were,
      respectively, 470% and 3700% higher than in lean rats (p <0.0001). Plasma ghrelin
      was significantly lower (-24.6%; p <0.02) than in lean rats. At 6 months of age,
      ghrelin increased in both genotypes but the difference was no more significant.
      The inverse correlations existing between ghrelin and either body weight (BW),
      insulin or leptin at 2 months of age were no more observable in 6-month-old rats.
      At 6 months of age, the lean rats had the same body weight as the 2-month-old
      obese rats. In these body weight-matched rats, ghrelin was not correlated with BW
      but it remained negatively correlated with insulin and leptin. At the same body
      weight, obese rats had a much lower plasma ghrelin than lean rats (717+/-42 vs.
      1754+/-83 pg/ml; p <0.0001). These data indicate that body composition rather
      than body weight is the primary factor for the down-regulation of the ghrelin
      system. This down-regulation constitutes a mechanism of defense of the organism
      against the development of obesity at least during the first part of life.

PMID- 15147949
TI  - Deletion of one copy of the p16INK4A tumor suppressor gene is implicated as a
      predisposing factor in pediatric leukemia.
AB  - The p16INK4A tumor suppressor gene is frequently disrupted by mutation or
      deletion in a wide range of cancer types, ranging from leukemia to cancers of the
      bladder, skin, lung, liver, and spleen. We have previously shown that deletion of
      at least one copy of the p16INK4A gene is associated with an increased risk of
      relapse in pediatric leukemia. Our data suggest that hemizygous p16INK4A deletion
      may be constitutional, conferring susceptibility to leukemia. Confirmation of
      this association is worthy of a larger study. Data from primary leukemia
      specimens are also presented here which examined the possibility that the
      remaining allele of the gene was inactivated by another mechanism such as
      mutation or was silenced by methylation. These possibilities were formally
      excluded in a case of hemizygous loss of the p16INK4A gene in leukemia,
      establishing that in this case the p16INK4A deletion was either semidominant or
      fully haploinsufficient for relapse susceptibility in this disease.
      Implementation of high throughput methods such as those used here for detecting
      hemizygous loss of tumor suppressor genes will become increasingly important for
      molecular diagnosis of cancer. This is particularly true for the emerging class
      of tumor suppressor genes where deletion of one allele is sufficient to confer
      cancer susceptibility or poor prognosis with standard treatment.

PMID- 15147950
TI  - Genetic evidence for involvement of two distinct nonhomologous end-joining
      pathways in repair of topoisomerase II-mediated DNA damage.
AB  - In vertebrate cells, DNA double-strand breaks are efficiently repaired by
      homologous recombination or nonhomologous end-joining (NHEJ). The latter pathway
      relies on Ku (the Ku70/Ku86 heterodimer), DNA-PKcs, Artemis, Xrcc4, and DNA
      ligase IV (Lig4). Here, we show that a human pre-B cell line nullizygous for Lig4
      exhibits hypersensitivity to topoisomerase II (Top2) inhibitors, demonstrating a
      crucial role for the NHEJ pathway in repair of Top2-induced DNA damage in
      vertebrates. We also show that in the chicken DT40 cell line, all NHEJ mutants
      (i.e., Ku70-, Lig4-, and DNA-PKcs-null cells) are equally hypersensitive to the
      Top2 inhibitor ICRF-193, indicating that the drug-induced damage is repaired by
      NHEJ involving DNA-PKcs. Intriguingly, however, DNA-PKcs-null cells display
      considerably less severe phenotype than other NHEJ mutants in terms of
      hypersensitivity to VP-16, a Top2 poison that stabilizes cleavable complexes. The
      results indicate that two distinct NHEJ pathways, involving or not involving DNA
      PKcs, are important for the repair of VP-16-induced DNA damage, providing
      additional evidence for the biological relevance of DNA-PKcs-independent NHEJ.
      Our results provide significant insights into the mechanisms of repair of Top2
      mediated DNA damage, with implications for chemotherapy involving Top2
      inhibitors.

PMID- 15147951
TI  - Characterization of SARS main protease and inhibitor assay using a fluorogenic
      substrate.
AB  - SARS main protease is essential for life cycle of SARS coronavirus and may be a
      key target for developing anti-SARS drugs. Recently, the enzyme expressed in
      Escherichia coli was characterized using a HPLC assay to monitor the formation of
      products from 11 peptide substrates covering the cleavage sites found in the SARS
      viral genome. This protease easily dissociated into inactive monomer and the
      deduced Kd of the dimer was 100 microM. In order to detect enzyme activity, the
      assay needed to be performed at micromolar enzyme concentration. This makes
      finding the tight inhibitor (nanomolar range IC50) impossible. In this study, we
      prepared a peptide with fluorescence quenching pair (Dabcyl and Edans) at both
      ends of a peptide substrate and used this fluorogenic peptide substrate to
      characterize SARS main protease and screen inhibitors. The fluorogenic peptide
      gave extremely sensitive signal upon cleavage catalyzed by the protease. Using
      this substrate, the protease exhibits a significantly higher activity (kcat = 1.9
      s(-1) and Km = 17 microM) compared to the previously reported parameters. Under
      our assay condition, the enzyme stays as an active dimer without dissociating
      into monomer and reveals a small Kd value (15 nM). This enzyme in conjunction
      with fluorogenic peptide substrate provides us a suitable tool for identifying
      potent inhibitors of SARS protease.

PMID- 15147952
TI  - Transcriptional repression of E2F gene by proteasome inhibitors in human
      osteosarcoma cells.
AB  - E2F family of transcription factors regulates the transcription of genes required
      for DNA synthesis. E2F is itself controlled by a series of transcriptional and
      post-transcriptional pathways. Here we provide evidence that proteasome inhibitor
      mediated E2F1 gene down-regulation is regulated by transcriptional events. Using
      the proteasome-specific inhibitors, MG132 and lactacystin, we show that the p53,
      the cdk inhibitors p21 and p27, and cyclin A are degraded by the ubiquitin
      proteasome pathway in human osteosarcoma cells. Interestingly, the expression
      levels of E2F1 and E2F2 are down-regulated by proteasome inhibitors. E2F promoter
      and RT-PCR assay clearly demonstrated that proteasome inhibitors could reduce E2F
      transcriptional activation. However, MG132-induced repression of E2F1 and E2F2 is
      not associated with ROS generation.

PMID- 15147953
TI  - Integrin-mediated mechanotransduction processes in TGFbeta-stimulated monolayer
      expanded chondrocytes.
AB  - Previous studies have demonstrated that passage in monolayer detrimentally
      affects the response of articular chondrocytes to the application of dynamic
      compression. Transforming growth factor beta (TGFbeta) is known to regulate
      metabolic processes in articular cartilage and can enhance the re-expression of a
      chondrocytic phenotype following monolayer expansion. The current study tests the
      hypothesis that TGFbeta also modulates the response of monolayer-expanded human
      chondrocytes to the application of dynamic compression, via an integrin-mediated
      mechanotransduction process. The data presented demonstrate that TGFbeta3
      enhanced 35SO4 and [3H]thymidine incorporation and inhibited nitrite release
      after 48 h of culture when compared to unsupplemented constructs. Dynamic
      compression also enhanced 35SO4 and [3H]thymidine incorporation and inhibited
      nitrite release in the presence of TGFbeta3. By contrast, dynamic compression did
      not alter these parameters in the absence of the growth factor. The addition of
      the peptide, GRGDSP, which acts as a competitive ligand for the alpha5beta1
      integrin, reversed the compression-induced stimulation of 35SO4 incorporation,
      [3H]thymidine incorporation, and suppression of nitrite release. No effect was
      observed when the control peptide, GRADSP, was used. The current data clearly
      demonstrate that the dynamic compression-induced changes observed in cell
      metabolism for human monolayer-expanded chondrocytes were dependent on the
      presence of TGFbeta3 and are integrin-mediated.

PMID- 15147954
TI  - Invasiveness of breast carcinoma cells and transcript profile: Eph receptors and
      ephrin ligands as molecular markers of potential diagnostic and prognostic
      application.
AB  - The Eph family of receptors, with 14 members in humans, makes up the largest
      group of receptor tyrosine kinases. These Eph receptors, along with their
      ligands, the 8 members of the ephrin family of ligands are involved in diverse
      developmental functions, including hindbrain development in vertebrates, tissue
      patterning, and angiogenesis. These Eph receptors and ephrin ligands have also
      been identified as important regulators in the development and progression of
      cancer. We have presented here a systematic and comprehensive investigation of
      the Eph/ephrin expression profiles of MCF-10A, MCF-7, and MDA-MB-231 cells
      representing normal breast, non-invasive breast tumor, and invasive tumor,
      respectively, based on their characteristic phenotypes in Matrigel matrix. The
      data have allowed us to correlate the gene expression profile with the cell
      phenotype that has potential application in tumor diagnostics. We demonstrate
      here that upregulation of EphA2, A7, A10, and ephrinA2 and B3 is likely involved
      in tumorigenesis and/or invasiveness, while downregulation of EphA1, A3, A4, A8,
      B3, B4, B6, and ephrinA1 and B1 may be particularly important in invasiveness.
      Based on these results we discuss the role of EphA2 and ephrinA1 combination in
      malignancy. The data have provided clues as to the importance of these molecules
      in the progression of breast cancer and specifically identified EphB6, a kinase
      deficient receptor, which is downregulated in the most aggressive cell line, as
      reported for several other cancer types including neuroblastoma and melanoma
      suggesting its potential as a prognostic indicator in breast cancer as well.

PMID- 15147955
TI  - The role of Clock in the plasticity of circadian entrainment.
AB  - The mammalian circadian clock lying in suprachiasmatic nucleus (SCN) is
      synchronized to about 24 h by the environmental light-dark cycle (LD). The
      circadian clock exhibits limits of entrainment above and below 24 h, beyond which
      it will not entrain. Little is known about the mechanisms regulating the limits
      of entrainment. In this study, we show that wild-type mice entrain to only an LD
      24 h cycle, whereas Clock mutant mice can entrain to an LD 24, 28, and 32 h
      except for LD 20 h and LD 36 h cycle. Under an LD 28 h cycle, Clock mutant mice
      showed a clear rhythm in Per2 mRNA expression in the SCN and behavior. Light
      response was also increased. This is the first report to show that the Clock
      mutation makes it possible to adapt the circadian oscillator to a long period
      cycle and indicates that the clock gene may have an important role for the limits
      of entrainment of the SCN to LD cycle.

PMID- 15147957
TI  - The influence of trace amount of calponin on the smooth muscle myosins in
      different states.
AB  - Calponin (CaP), a thin filament-associated protein, plays an important role in
      the regulation of smooth muscle contractility. It has been known that CaP
      inhibits the actin-activated myosin MgATPase activity via binding to F-actin, and
      stimulates myosin MgATPase activity via binding to myosin. Our recent study
      revealed a new phenomenon that trace amount of CaP (TAC) could influence the
      function of different states of myosin. Our data showed that in the absence of
      actin, CaP, even in the concentration of 0.0001 microM, significantly increased
      the precipitations of 1 microM unphosphorylated myosin, Ca(2+)-CaM dependently,
      and independently phosphorylated myosin by MLCK, and stimulated the MgATPase
      activities of these myosins slightly but significantly. However, no obvious
      change of precipitation of myosin phosphorylated by PKA was observed, indicating
      the relative selective effect of TAC. In the presence of actin, myosin, and TAC,
      the increase of myosin precipitation was abolished, and no obvious changes of
      actin precipitations and actin-activated myosin MgATPase activities were observed
      implicating the highly efficiency of TAC on myosin being present in the absence
      of actin. Although we cannot give conclusive comments to our results, we propose
      that the high efficiency of TAC-myosin interaction is present in the regulation
      of the function of myosin when actin is dissociated from myosin, even if
      CaP/myosin ratio is very low; this high efficient interaction between TAC and
      myosin can be abolished by actin. However, why and how TAC can possess such a
      high efficiency to influence myosin and how the physiological significance of the
      high efficiency of TAC is in regulating the interaction between myosin and actin
      remain to be investigated.

PMID- 15147956
TI  - FLT3 ligand regulates apoptosis through AKT-dependent inactivation of
      transcription factor FoxO3.
AB  - Proliferation, differentiation, and survival of hematopoietic cells are regulated
      by cytokines, acting through specific receptors. FLT3 ligand (FL) is one of the
      most important cytokines for regulation of the hematopoietic system, and its
      receptor FLT3 is expressed on both stem cells and progenitors. Regulation of
      Forkhead transcription factors has been described as an important mechanism to
      control apoptosis and cell cycle progression in hematopoietic progenitors. Here
      we report that FL induces AKT/PKB activation, which in turn phosphorylates and
      thereby inactivates the Forkhead protein FoxO3 in the progenitor cell line FDC-P1
      stably expressing murine FLT3 receptor. Phosphorylation of AKT and FoxO3 was
      blocked by the PI-3 kinase inhibitor LY294002 but not by the MAP kinase inhibitor
      PD98059. Expression of a mutated FoxO3, in which all three inhibitory
      phosphorylation sites were mutated to alanine, led to rapid increase of apoptotic
      cells in the presence of FL. These results suggest that FL-induced regulation of
      apoptosis is executed by FoxO3.

PMID- 15147958
TI  - Differential effects of vanadate on UDP-N-acetylglucosaminyl transferase activity
      derived from cytosol and nucleosol.
AB  - UDP-N-acetylglucosaminyl transferase (OGT) is a key enzyme of a novel signal
      transduction pathway that regulates protein function through O-linked
      glycosylation. In the current study, we found that sodium vanadate potently
      inhibits OGT activity in brain cytosol (IC50 = 55 microM) and nucleosol (IC50 =
      150 microM), but fails to alter activity of a related enzyme (UDP
      galactosyltransferase). Vanadate also inhibits OGT activity in cytosol (IC50 of
      2.3 microM) and nucleosol (IC50 of 130) derived from a stable HeLa cell line that
      overexpresses OGT. When HeLa cytosol was immunopurified to separate OGT from
      other cellular proteins, vanadate still inhibited OGT activity (IC50 = 2 microM).
      We conclude that OGT derived from cytosol exhibits greater vanadate sensitivity
      than nucleosol OGT and that a large difference exists (25-fold) in vanadate
      sensitivity when comparing OGT activity in different cell types (IC50 of 55
      microM for brain cytosol vs. 2.3 microM for HeLa cytosol). Understanding the
      mechanism(s) by which a tyrosine phosphatase inhibitor differentially reduces OGT
      activity should lead to new insights into OGT function and regulation.

PMID- 15147959
TI  - Oncofetal splice-pattern of the human H19 gene.
AB  - H19 is an imprinted gene that demonstrates maternal monoallelic expression in
      fetal tissues and in some cancers, and very likely does not code for a protein.
      H19 is involved in the regulation of cell proliferation, embryonic growth, and
      differentiation through upstream and downstream cis elements that influence the
      expression of IGF2, a closely physically linked gene, and also through its RNA
      involved in metastasis and angiogenic processes. We report the identification of
      an alternatively spliced variant of H19 RNA that lacks part of exon 1. This
      variant was detected in human embryonic and placental tissues, but not in bladder
      or hepatocellular carcinomas. A very low level of this variant was also detected
      in colon carcinoma. The observed pattern of expression suggests that this splice
      variant is a developmentally regulated H19 gene transcript.

PMID- 15147960
TI  - Influence of cholesterol and ergosterol on membrane dynamics: a fluorescence
      approach.
AB  - Sterols are essential membrane components of eukaryotic cells and are important
      for membrane organization and function. Cholesterol is the most representative
      sterol present in higher eukaryotes. It is often found distributed non-randomly
      in domains or pools in biological and model membranes. Cholesterol-rich
      functional microdomains (lipid rafts) are often implicated in cell signaling and
      membrane traffic. Interestingly, lipid rafts have also recently been isolated
      from organisms such as yeast and Drosophila, which have ergosterol as their major
      sterol component. Although detailed biophysical characterization of the effect of
      cholesterol on membranes is well documented, the effect of ergosterol on the
      organization and dynamics of membranes is not very clear. We have monitored the
      effect of cholesterol and ergosterol on the dynamic properties of both fluid
      (POPC) and gel (DPPC) phase membranes utilizing the environment-sensitive
      fluorescent membrane probe DPH. Our results from steady state and time-resolved
      fluorescence measurements show, for the first time, differential effects of
      ergosterol and cholesterol toward membrane organization. These novel results are
      relevant in the context of lipid rafts in ergosterol-containing organisms such as
      Drosophila which maintain a low level of sterol compared to higher eukaryotes.

PMID- 15147961
TI  - Characterization of RNA interference in rat PC12 cells: requirement of GERp95.
AB  - Double-stranded RNA can initiate post transcriptional gene silencing in mammalian
      cell cultures via a mechanism known as RNA interference (RNAi). The sequence
      specific degradation of homologous mRNA is triggered by 21-nucleotide RNA
      duplexes termed short interfering RNA (siRNA). The homologous strand of the siRNA
      guides a multi-protein complex, RNA-induced silencing complex (RISC), to cleave
      target mRNA. Although the exact function and composition of RISC is still
      unclear, it has been shown to include several proteins of the Argonaute protein
      family. Here we report of a robust system to achieve RNAi in a cultured rat
      neuronal cell line, PC12. Targeting of neuropeptide Y mRNA by synthetic siRNA
      results in knock down of the mRNA levels with an IC50 of approximately 0.1 nM.
      The mRNA knockdown lasts for at least 96 h and is not dependent on protein
      synthesis. Further, PC12 cells were ablated of the rat Golgi-ER protein 95 kDa
      (GERp95), an Argonaute family protein, by siRNA methodology. After GERp95
      ablation, sequential knockdown of NPY by siRNA was shown to be impaired. Thus, we
      report that the GERp95 protein is functionally required for RNAi targeting NPY in
      rat PC12 cells.

PMID- 15147962
TI  - Aire downregulates multiple molecules that have contradicting immune-enhancing
      and immune-suppressive functions.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a
      systemic disease with autoimmune characteristics caused by mutations in a single
      gene called AIRE. Although a defect in negative selection has been emphasized for
      the pathogenesis of the autoimmune symptoms on the basis of studies of Aire
      targeted mice, the function of the gene in the peripheral immune system and the
      cause of immunodeficiency noted in the disease have not been clarified yet. In
      this study, we demonstrated using murine Aire transfectants that Aire
      downregulates IL-1 receptor antagonist (IL-1Ra), which is important for immune
      suppression, and major histocompatibility complex (MHC) class II molecules, which
      are critical for acquired immunity. It was surprising to learn that Aire, which
      has been supposed to positively regulate transcription, downregulates multiple
      molecules. This downregulation of IL-1Ra and MHC class II molecules seems to be
      caused by the competition for transcriptional coactivator, CREB-binding protein
      (CBP), and may explain part of the contradictory (i.e., both autoimmune and
      immunodeficient) nature of APECED.

PMID- 15147963
TI  - Effects of glucocorticoids on the respiratory burst of Chlamydia-primed THP-1
      cells.
AB  - We previously observed that the respiratory burst of human monocytes (THP-1 cell
      line) triggered by phorbol myristate acetate was strongly enhanced by a priming
      of the cells by Chlamydia pneumoniae [Biochem. Biophys. Res. Commun. 287 (2001)
      781]. We describe here the modifications of the responses of Chlamydia-primed THP
      1 cells to hydrocortisone (HCT) and methylprednisolone (MPL). HCT and MPL
      inhibited the production of the cytokines TNFalpha and IL-8. But HCT, which
      inhibited the respiratory burst in LPS-primed monocytes, paradoxically stimulated
      the phenomenon in Chlamydia-primed cells; MPL exerted no significant effect. Both
      glucocorticoids did not significantly modify the triggering effect of Chlamydia
      on NF-kappaB binding activity. On the expression of p22(phox), a protein subunit
      of the NADPH oxidase, HCT had an increasing and MPL a decreasing effect.
      Glucocorticoids thus had unexpected effects on the inflammatory response of
      Chlamydia-primed monocytes.

PMID- 15147964
TI  - Biodistribution of intracellularly acting peptides conjugated reversibly to Tat.
AB  - Intracellularly acting peptide modulators of signaling enzymes provide a powerful
      means to regulate signaling events. Delivery of peptides into cells is
      facilitated by conjugation to carrier peptides, such as Tat. When peptides are
      irreversibly conjugated to Tat, Tat-mediated subcellular localization may
      predominate, resulting in mislocalization of the peptide cargo. We have used
      intracellularly acting peptides, conjugated to Tat by a disulfide bond, to
      modulate protein kinase C (PKC) signaling; these PKC-modulating peptides are
      released from Tat upon intracellular delivery. Previously, the distribution of
      these peptides within tissue and throughout the body had not been demonstrated.
      We show here intravascular delivery of a PKC-peptide, reversibly conjugated to
      Tat, resulted in distribution throughout cardiac tissue. In addition, a single
      injection resulted in selective modulation of PKC activity in many organs.
      Therefore, intracellularly acting peptide modulators of signaling enzymes,
      reversibly conjugated to Tat, have extensive biodistribution and can be used to
      modulate signaling pathways in vivo.

PMID- 15147965
TI  - Neural precursors express multiple chondroitin sulfate proteoglycans, including
      the lectican family.
AB  - Chondroitin sulfate proteoglycans (CSPGs) abnormally accumulate in cerebrospinal
      fluid (CSF) of both human neonates with preterm hydrocephalus, and P8
      hydrocephalic mice. We hypothesized CSF CSPGs are synthesized by neural
      precursors, separated from ventricular CSF by ependyma, which is often disrupted
      in hydrocephalus. Western blotting demonstrates that neural precursors cultured
      as neurospheres secrete CSPGs (> 30 microg/ml) into their media which appear to
      be very similar to these CSF CSPGs. Some CSPGs bear the stage-specific embryonic
      antigen-1 (ssea-1), associated with embryonic/neural stem cells. Neurospheres
      transcribe many CSPG genes, including the entire aggrecan/lectican family,
      phosphacan, and tenascin. Phosphacan can be detected in media by Western
      blotting. Aggrecan can be detected in media after purification using hyaluronic
      acid affinity chromatography. During differentiation, neurospheres downregulate
      CSPGs. This is the first report to show that proliferating neural precursors
      synthesize lecticans, including aggrecan, which are downregulated with
      differentiation. These observations suggest novel links between CSPGs and CNS
      precursor biology.

PMID- 15147967
TI  - Vital roles of an interhelical insertion in catalase-peroxidase bifunctionality.
AB  - The loop connecting the F and G helices of catalase-peroxidases contains a
      approximately 35 amino acid structure (the FG insertion) that is absent from
      monofunctional peroxidases. These two groups of enzymes share highly similar
      active sites, yet the monofunctional peroxidases lack appreciable catalase
      activity. Thus, the FG insertion may serve a role in catalase-peroxidase
      bifunctionality, despite its peripheral location relative to the active site. We
      produced a variant of Escherichia coli catalase-peroxidase (KatG) lacking its FG
      insertion (KatG(DeltaFG)). Absorption spectra indicated the heme environment of
      KatG(DeltaFG) was highly similar to wild-type KatG, but the variant retained only
      0.2% catalase activity. In contrast, the deletion reduced peroxidase activity by
      only 50%. Kinetic parameters for the peroxidase and residual catalase activities
      of KatG(DeltaFG) as well as pH dependence studies suggested that the FG insertion
      supports hydrogen-bonded networks critical for reactions involving H2O2. The
      structure also appears to regulate access of electron donors to the active site.

PMID- 15147966
TI  - Osteoporosis in MCHR1-deficient mice.
AB  - It is well recognized that the hypothalamus is of central importance in the
      regulation of food intake and fat mass. Recent studies indicate that it also
      plays an important role in the regulation of bone mass. Melanin concentrating
      hormone (MCH) is highly expressed in the hypothalamus and has been implicated in
      regulation of energy homeostasis. We developed MCHR1 inactivated mice to evaluate
      the physiological role of this receptor. Interestingly, the MCHR1(-/-) mice have
      osteoporosis, caused by a reduction in the cortical bone mass, while the amount
      of trabecular bone is unaffected. The reduction in cortical bone mass is due to
      decreased cortical thickness. Serum levels of c-telopeptide, a marker of bone
      resorption, are increased in MCHR1(-/-) mice, indicating that the MCHR1(-/-) mice
      have a high bone turnover osteoporosis. In conclusion, the MCHR1(-/-) mice have
      osteoporosis, indicating that MCHR1-signalling is involved in a tonic stimulation
      of bone mass.

PMID- 15147968
TI  - Post-transcriptional regulation of glucose transporter-1 by an AU-rich element in
      the 3'UTR and by hnRNP A2.
AB  - Glucose transporter-1 (GLUT1) mediates uptake of glucose and is up-regulated in
      some cancers. The amount of this membrane protein is regulated by a post
      transcriptional mechanism in which mRNA binding proteins recognize cis-acting
      elements in the 3'-untranslated (3'UTR) of the mRNA. To identify cis elements in
      GLUT1 mRNA we introduced 3'UTR sequences into the 3'UTR of the luciferase gene in
      a reporter construct. A 30 nt adenosine-uridine-rich element ("GLUT1 AURE")
      inhibited luciferase activity in HEK-293 cells. This inhibitory effect was
      confirmed by deleting the GLUT1 AURE from a reporter containing the full-length
      3'UTR. Deletion of the GLUT1 AURE caused reporter activity to increase. Deletion
      of a larger fragment ("Bsu" region) containing the GLUT1 AURE increased reporter
      activity still further, suggesting that there are additional cis elements in the
      GLUT1 mRNA. The GLUT1 AURE was also active in GBM-T98G glioblastoma cells. Next,
      we tested the action of a trans-acting factor, hnRNP A2, on GLUT1 gene
      expression. We show that a cytoplasmic-localizing isoform of hnRNP A2 binds human
      GLUT1 RNA by gel-shift assay and by UV-crosslinking. Finally, over-expression of
      the hnRNP A2 isoform inhibited GLUT1 reporter expression in GBM-T98G cells. These
      results identify the AURE cis element in human GLUT1 mRNA and show that hnRNP A2
      acts on GLUT1 mRNA to inhibit expression of GLUT1 in a brain cancer cell line.

PMID- 15147969
TI  - Arylalkylamine N-acetyltransferase gene expression in retina and pineal gland of
      rats under various photoperiods.
AB  - The present study examines how the circadian oscillators in the retina and the
      suprachiasmatic nucleus (SCN) respond to changes in photoperiod. Arylalkylamine N
      acetyltransferase (aa-nat) gene expression studied by quantitative RT-PCR
      revealed that in adult Sprague-Dawley rats kept under different light-dark (LD)
      cycles for two weeks the temporal pattern of AA-NAT mRNA expression was identical
      in retina and pineal gland. In both tissues, the time span between the onset of
      darkness and the nocturnal rise in AA-NAT mRNA expression was 3 h under LD 20:4,
      6 h under LD 12:12, and 15 h under LD 4:20. As aa-nat expression in the pineal
      gland is regulated by the circadian oscillator in SCN, the results suggest that
      the photoperiodic differences accompanying the seasons of the year are imprinted
      in more than one oscillator and that this may accentuate the important message
      regarding 'time of year.'

PMID- 15147970
TI  - Absence of NADH channeling in coupled reaction of mitochondrial malate
      dehydrogenase and complex I in alamethicin-permeabilized rat liver mitochondria.
AB  - A simple in situ model of alamethicin-permeabilized isolated rat liver
      mitochondria was used to investigate the channeling of NADH between mitochondrial
      malate dehydrogenase (MDH) and NADH:ubiquinone oxidoreductase (complex I).
      Alamethicin-induced pores in the mitochondrial inner membrane allow effective
      transport of low molecular mass components such as NAD+/NADH but not soluble
      proteins. Permeabilized mitochondria demonstrate high rates of respiration in the
      presence of malate/glutamate and NAD+ due to coupled reaction between MDH and
      complex I. In the presence of pyruvate and lactate dehydrogenase, an
      extramitochondrial competitive NADH utilizing system, respiration of
      permeabilized mitochondria with malate/glutamate and NAD+ was completely
      abolished. These data are in agreement with the free diffusion of NADH and do not
      support the suggestion of direct channeling of NADH from MDH to complex I.

PMID- 15147971
TI  - A protective role for zinc on intestinal peroxidative damage during oral iron
      repletion.
AB  - Oral iron-supplementation is a general practice to correct iron deficiency
      anemia. Exposure of iron-deficient intestine to large doses of iron is known to
      induce oxidative damage, leading to loss of functional integrity, and reduced
      mucosal cell turnover. Conditioning of intestine with anti-oxidants during iron
      administration was shown to suppress iron-induced oxidative damage. Zinc is known
      to protect cells from peroxidative damage by inducing metallothionein and
      maintaining the sulfhydryl group stability. Nevertheless, co-administration of
      iron and zinc may antagonize each other with respect to absorption. In the
      present study, we show that combined supplementation of iron and zinc though
      marginally inhibits iron uptake significantly attenuates the oxidative stress by
      induction of metallothionein and elevating the levels of GSH. Further, presence
      of zinc in situ reduced the iron-induced hydroxyl radical production in the
      intestinal mucosa, as assessed by EPR spectroscopy. These results strongly
      suggest a protective role for zinc on iron-induced oxidative stress, which might
      have implications in anemia control programs.

PMID- 15147973
TI  - Bisphenol A, an environmental endocrine-disrupting chemical, inhibits hypoxic
      response via degradation of hypoxia-inducible factor 1alpha (HIF-1alpha):
      structural requirement of bisphenol A for degradation of HIF-1alpha.
AB  - Bisphenol A (BpA), an endocrine-disrupting chemical, is known to be a
      xenoestrogen and to affect the reproductive functions of animals. Recent reports
      have documented BpA-induced developmental abnormalities in the neuronal systems
      of humans and animals, and these effects appear to be non-estrogenic. In this
      study, we found that BpA inhibited the hypoxic response of human hepatoma cells.
      The expression of hypoxic response genes such as the erythropoietin (EPO) gene is
      done via a hypoxia inducible factor 1 (HIF-1)-dependent signaling pathway. To
      investigate possible structural requirements for this inhibitory effect, several
      BpA analogs were synthesized and added to this system. The blocking of two phenol
      groups in BpA did not change the effect, but the inhibition completely
      disappeared by the removal of two central methyl groups in BpA (the resulting
      compound is designated BpF). BpA, but not BpF, promoted degradation of the HIF
      1alpha protein, which is a component of HIF-1, followed by inhibition of EPO
      induction. An immunoprecipitation assay indicated that BpA dissociated heat shock
      protein 90 (Hsp90) from HIF-1alpha and destabilized HIF-1alpha protein. HIF
      1alpha is usually degraded first by ubiquitination and then by the proteasome
      pathway. Cobalt ion inhibits ubiquitination of HIF-1alpha and stabilizes it. In
      the present study, BpA promoted HIF-1alpha degradation in the presence of cobalt
      and in the presence of proteasome inhibitor. These results suggest that BpA
      degraded HIF-1alpha via a currently unknown pathway, and that this phenomenon
      required two methyl groups in BpA.

PMID- 15147974
TI  - Orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase
      exist as multienzyme complex in human malaria parasite Plasmodium falciparum.
AB  - Plasmodium falciparum, the causative agent of the most lethal form of human
      malaria, totally depends on de novo pyrimidine biosynthetic pathway. Orotate
      phosphoribosyltransferase (OPRT) and orotidine 5'-monophosphate decarboxylase
      (OMPDC), the fifth and sixth enzymes in the pathway catalyzing formation of
      uridine 5'-monophosphate (UMP), remain largely uncharacterized in the protozoan
      parasite. In this study, we achieved purification of OPRT and OMPDC to near
      homogeneity from P. falciparum cultivated in vitro. The OPRT and OMPDC activities
      were co-eluted in all chromatographic columns during purification, suggesting the
      purified proteins exist as a multienzyme complex with a molecular mass of 140+/-8
      kDa and contain two subunits each of OPRT and OMPDC. Monomeric forms of OPRT and
      OMPDC had molecular masses of 32+/-3 and 38+/-3 kDa, respectively, in agreement
      with those of proteins predicted from P. falciparum genome database.
      Interestingly, kinetic parameters and inhibitory constants of both OPRT and OMPDC
      activities were found to be different to those of the bifunctional human red cell
      UMP synthase. Our evidence provides the first example of OPRT and OMPDC existing
      as a multienzyme complex.

PMID- 15147972
TI  - Altered oxidative stress response of the long-lived Snell dwarf mouse.
AB  - Several single gene mutations in mice that increase the murine life span have
      been identified, including the Pit-1 mutation which results in the Snell dwarf
      (Pit1(dw/dw)), however, the biological mechanism of this life-span extension is
      still unclear. Based on studies that show oxidative stress plays an important
      role in the aging process, we hypothesized that the increased longevity seen in
      Snell dwarf mice may result from a resistance to oxidative stress. We report that
      Snell dwarf mice respond to oxidative stress induced by 3-NPA differently than
      their wild type littermates. This altered response results in diminished
      activation of the MEK-ERK kinase cascade and virtually no phosphorylation of c
      Jun at Ser63 in dwarf mice after 3-NPA treatment, despite a robust
      phosphorylation of Ser63 in wild type mice. We propose that this altered
      management of oxidative stress in dwarf mice is partially responsible for the
      increased longevity in Snell dwarf mice.

PMID- 15147975
TI  - Biological activity of a fragment of insulin.
AB  - Insulin controls or alters glucose, protein, and fat metabolism as well as other
      cellular functions. Insulin binds to a specific receptor on the cell membrane
      initiating a protein phosphorylation cascade that controls glucose uptake and
      metabolism and long-term effects such as mitogenesis. This process also initiates
      insulin uptake and ultimate cellular metabolism in all insulin sensitive cells.
      The effects of insulin on other cellular metabolic properties have not been
      clearly related to this mechanism. Here we show that intracellular metabolism of
      insulin may be related to some aspects of insulin actions, specifically control
      of fat metabolism. A normal intracellular degradation product of insulin has been
      synthesized and tested for actions on fat turnover in cultured adipocytes. This 7
      peptide, B-chain fragment (HLVEALY) inhibits both basal and stimulated lipolysis
      as measured by glycerol release, but does not inhibit FFA release because of a
      lack of effect on FFA reesterification in the adipocyte. HLVEALY also enhances
      insulin's effects on lipogenesis. This study shows that a fragment of insulin
      produced by the action of the insulin-degrading enzyme has both independent
      biological effects and interactions with insulin. This supports a biologically
      important effect of insulin metabolism and insulin degradation products on
      insulin action on non-glucose pathways.

PMID- 15147976
TI  - Evidences showing ultraviolet-B radiation-induced damage of DNA in cyanobacteria
      and its detection by PCR assay.
AB  - Impact of ultraviolet-B radiation in causing the damages to the DNA of the
      cyanobacterium, Anabaena strain BT2 has been investigated. Exposure of genomic
      DNA (in vitro) to UV-B radiation for 1 h did not cause any shift in the
      absorption peak (lambda(max)) but more than 30% increase in absorbance was
      noticed in comparison to untreated control DNA (no exposure to UV-B). This
      increase in absorbance in a way may be comparable to typical hypochromic effect
      but there was no decrease in absorbance following transfer of UV-B-treated DNA to
      fluorescent light or in the dark. That the damaging effect of UV-B radiation on
      native structure of DNA is indeed real was also evident from the PCR-based assay
      such as RAPD, rDNA amplification, and ARDRA. Template activity of UV-B-treated
      genomic DNA was drastically inhibited, there was no amplification in RAPD assay
      after prior exposure of DNA to UV-B for 60 min. Only one band of approximately
      400 bp was observed even after 60 min of exposure which suggests that certain
      segment of DNA strand is resistant to UV-B effects. Similar to the effects on
      RAPD profile, amplification of rDNA was significantly inhibited following
      exposure of genomic DNA to UV-B. Our findings clearly demonstrate that UV-B does
      affect the DNA of cyanobacteria and the killings of these microbes might be due
      to the irreversible damages caused to DNA by this high energy radiation. It is
      felt that PCR assay may be conveniently used for screening the damages caused to
      DNA by UV-B radiation in cyanobacteria and other microorganisms.

PMID- 15147977
TI  - Alterations of O-glycosylation, cell wall, and mitochondrial metabolism in
      Kluyveromyces lactis cells defective in KlPmr1p, the Golgi Ca(2+)-ATPase.
AB  - In yeast the P-type Ca(2+)-ATPase of the Golgi apparatus, Pmr1p, is the most
      important player in calcium homeostasis. In Kluyveromyces lactis KlPMR1
      inactivation leads to pleiotropic phenotypes, including reduced N-glycosylation
      and altered cell wall morphogenesis. To study the physiology of K. lactis when
      KlPMR1 was inactivated microarrays containing all Saccharomyces cerevisiae coding
      sequences were utilized. Alterations in O-glycosylation, consistent with the
      repression of KlPMT2, were found and a terminal N-acetylglucosamine in the O
      glycans was identified. Klpmr1Delta cells showed increased expression of PIRs,
      proteins involved in cell wall maintenance, suggesting that responses to cell
      wall weakening take place in K. lactis. We found over-expression of KlPDA1 and
      KlACS2 genes involved in the Acetyl-CoA synthesis and down-regulation of KlIDP1,
      KlACO1, and KlSDH2 genes involved in respiratory metabolism. Increases in oxygen
      consumption and succinate dehydrogenase activity were also observed in mutant
      cells. The described approach highlighted the unexpected involvement of KlPMR1 in
      energy-yielding processes.

PMID- 15147978
TI  - A constitutive super-enhancer: homologous region 3 of Bombyx mori
      nucleopolyhedrovirus.
AB  - Transient expression assays were carried out to assess the transcriptional
      enhancement from the immediate-early gene (ie-1) promoters by cis-linked Bombyx
      mori nucleopolyhedrovirus (BmNPV) homologous region-3 (hr3). The ie-1 promoters
      were derived from Autographa californica multinucleocapsid nucleopolyhedrovirus
      (AcMNPV) and BmNPV. Hr3 was placed downstream of the luciferase (luc) gene, the
      resulting plasmids were used to transfect the Spodoptera frugiperda (Sf-21),
      Bombyx mori (Bm-5, Bm-N) cell lines and 5th instar silkworm larvae mediated by
      lipofectin. The results revealed that hr3 could stimulate the transcription of
      homologous BmNPV ie-1 promoter 1970, 2421, 683, and 1059 folds, and the
      heterologous AcMNPV ie-1 promoter 6462, 4046, 6980, and 605 folds, respectively.
      These results implied that hr3 was a super enhancer which could function both in
      vitro and in vivo. The 30-bp imperfect palindrome in hr3 was proved to be the
      essential structure for enhancing function of hr3. The utilizing of this promoter
      enhancer combination in the baculovirus expression vector system (BEVS) was also
      carried out to further confirm the function of hr3 enhancer.

PMID- 15147979
TI  - EWS differentially activates transcription of the Brn-3a long and short isoform
      mRNAs from distinct promoters.
AB  - Brn-3a long and short isoforms are known to be encoded by two distinct mRNA
      transcripts derived from a single gene. Here we report that transcription of the
      two isoforms is differentially regulated. The short isoform has its own promoter,
      though many elements in the 5' regulatory region are shared. The protein product
      of the EWS gene, translocations of which are associated with the Ewing's sarcoma
      family of tumours, is known to interact with Brn-3a via a direct protein-protein
      interaction. Here we show that EWS also regulates Brn-3a expression in an isoform
      specific manner. The implications of these results are discussed in terms of the
      functional role of EWS and the distinct functional activities of the two isoforms
      of Brn-3a.

PMID- 15147980
TI  - Activation of simian virus 40 promoter by HTLV-I Tax protein: role of NF-kappaB
      and CBP.
AB  - HTLV-I is implicated with adult T-cell leukemia and certain other clinical
      disorders. The viral Tax protein is regarded as a key element in HTLV-I
      pathogenicity due to its ability to activate a wide variety of cellular
      regulatory factors. As such, Tax may likely activate also latent infection of
      certain other pathogenic viruses whose expression is modulated by cellular
      transcription factors. Therefore, investigation of Tax effect on the expression
      of these viruses is of particular clinical importance, since HTLV-I infection of
      carriers harboring such latent viruses may trigger their related diseases. In
      this study we focused on simian virus 40 and demonstrated that Tax activates the
      promoter of this virus through NF-kappaB-associated pathway. Furthermore, we show
      that this activation requires an interaction of the NF-kappaB factor p65(RelA)
      with CBP, which depends on PKA-mediated phosphorylation of p65(RelA). Finally,
      the present study proves that the nuclear Tax plays a critical role in Tax
      induced NF-kappaB-mediated SV40 activation.

PMID- 15147981
TI  - A novel mitogenic and antiproliferative lectin from a wild cobra lily, Arisaema
      flavum.
AB  - A novel lectin having specificity towards a complex glycoprotein asialofetuin was
      purified from tubers of Arisaema flavum (Schott.) by affinity chromatography on
      asialofetuin-linked amino-activated silica beads. A. flavum gave a single peak on
      HPLC size exclusion and a single band on non-denatured PAGE at pH 4.5. The
      molecular mass of the lectin, as determined by gel filtration chromatography, was
      56 kDa. In SDS-PAGE, pH 8.3, the lectin migrated as a single band of 13.5 kDa,
      under reducing and non-reducing conditions, indicating the homotetrameric nature.
      A. flavum lectin (AFL) readily agglutinated rabbit, rat, sheep, goat, and guinea
      pig erythrocytes but not human ABO blood group erythrocytes even after
      neuraminidase treatment. This lectin is stable up to 55 degrees C and does not
      require metal ions for its hemagglutination activity. AFL was completely devoid
      of sulphur containing amino acids and was rich in aspartic acid and glycine. In
      Oucterlony's double immunodiffusion, the antisera raised against A. flavum lectin
      showed distinct lines of identity with those of other araceous lectins. AFL
      showed potent mitogenic activity towards BALB/c splenocytes and human lymphocytes
      in comparison to Con A, a well-known plant mitogen. AFL also showed significant
      in vitro antiproliferative activity towards J774 and P388D1 murine cancer cell
      lines.

PMID- 15147982
TI  - Streptozotocin directly impairs cardiac contractile function in isolated
      ventricular myocytes via a p38 map kinase-dependent oxidative stress mechanism.
AB  - Streptozotocin (STZ) has long been used to induce experimental diabetes mellitus
      to study diabetic complications such as diabetic cardiomyopathy. However, direct
      impact of STZ on cardiac function is unknown. This study was designed to evaluate
      the cardiac contractile effect of STZ in isolated adult rat ventricular myocytes.
      Contractile properties were assessed with an IonOptix MyoCam system including
      peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and
      maximal velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca2+
      handling was evaluated with the fluorescent dye fura-2. Acute exposure of STZ
      (10(-9)-10(-5) M) depressed PS, prolonged TR90, and decreased electrically
      stimulated intracellular Ca2+ rise in a concentration-dependent manner. TPS,+/
      dL/dt, resting intracellular Ca2+ level, and intracellular Ca2+ clearing rate
      were unaffected. The STZ-induced mechanical alterations were alleviated by the
      antioxidant vitamin C (100 microM) and the p38 MAP kinase inhibitor SB203580 (1
      microM). 2', 7'-Dichlorofluorescein diacetate staining revealed enhanced
      production of reactive oxygen species following STZ treatment, which was
      prevented by either vitamin C or SB203580. Collectively, our data provided
      convincing evidence that the tool drug for experimental diabetes STZ may itself
      cause deleterious cardiac contractile dysfunction via an oxidative stress and p38
      MAP kinase-dependent mechanism. Thus, caution should be taken when assessing
      diabetic heart complications using STZ-induced diabetic models.

PMID- 15147983
TI  - Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba
      extract.
AB  - The Ginkgo biloba extract EGb761 was tested for its ability to inhibit the major
      human cytochrome P450 enzymes (CYPs). The full extract was found to strongly
      inhibit CYP2C9 (Ki = 14+/- 4 microg/mL), and to a lesser extent, CYP1A2 (Ki = 106
      +/- 24 microg/mL), CYP2E1 (Ki = 127 +/- 42 microg/mL), and CYP3A4 (Ki = 155 +/-
      43 microg/mL). The terpenoidic and flavonoidic fractions of the extract were
      tested separately against the same P450s to identify the source of inhibition by
      EGb761. The terpenoidic fraction inhibited only CYP2C9 (Ki = 15 +/-6 microg/mL)
      whereas the flavonoidic fraction of EGb761 showed high inhibition of CYP2C9,
      CYP1A2, CYP2E1, and CYP3A4 (Ki's between 4.9 and 55 microg/mL). The flavonoidic
      fraction was further fractionated using extraction and chromatography. Inhibition
      studies indicated that the majority of these fractions inhibited P450s at a
      significant level (IC50 < 40 microg/mL).

PMID- 15147984
TI  - Identification of nuclear localisation sequences in spastin (SPG4) using a novel
      Tetra-GFP reporter system.
AB  - Mutations in the human spastin gene (SPG4) cause the most prevalent form of
      autosomal dominant hereditary spastic paraplegia (HSP), a neurodegenerative
      disorder characterised by progressive weakness and spasticity of the lower limbs.
      We address the question of intracellular localisation of spastin. Using
      polyclonal antibodies against N-terminal spastin sequences, we find that the
      native protein is localised in both the perinuclear cytoplasm and the nucleus. To
      identify structural motifs within the protein that can explain entry into the
      nucleus, we developed a reporter system to test nuclear localisation sequence
      (NLS)-functionality based on four in-frame fused copies of green fluorescent
      protein. Using this novel tool we demonstrate that spastin carries two NLSs
      located in exons 1 and 6. Both are independently functional in mediating nuclear
      entry.

PMID- 15147986
TI  - Understanding the role of immune regulation in wound healing.
AB  - The immune system plays an integral role in successful wound healing. In addition
      to contributing to host defenses and inflammation, immune cells are critical
      regulators of wound healing through the secretion of cytokines, lymphokines, and
      growth factors. We review the mechanisms by which the immune system regulates
      wound healing.

PMID- 15147985
TI  - Protocol for treatment of diabetic foot ulcers.
AB  - Each year, 82,000 limb amputations are performed in patients with diabetes
      mellitus. The majority of these amputations could be avoided by following strict
      protocols. The collective experience treating patients with neuropathic diabetic
      foot ulcers of 4 major diabetic foot programs in the United States and Europe
      were analyzed. The following protocol has been developed for patients with
      diabetic foot ulcers: (1) measurement of the wound by planimetry; (2) optimal
      glucose control; (3) surgical debridement of all hyperkeratotic, infected, and
      nonviable tissue; (4) systemic antibiotics for deep infection, drainage, and
      cellulitis; (5) offloading; (6) moist-wound environment; and (7) treatment with
      growth factors and/or cellular therapy if the wound is not healing after 2 weeks
      with this protocol and a new epithelial layer is not forming. In addition, the
      pathogenesis of diabetic foot ulcers is discussed, as well as the associated
      costs and complications, including amputation. Debridement, wound-bed
      preparation, antibiotics, various types of dressings, biological therapies,
      growth factors, and offloading are described as treatment modalities for patients
      with diabetic foot ulcers. In diabetic foot ulcers, availability of the above
      modalities, in combination with early recognition and comprehensive treatment,
      ensure rapid healing and minimize morbidity, mortality, and costs, as well as
      eliminate amputation in the absence of ischemia and osteomyelitis.

PMID- 15147987
TI  - Pressure and the diabetic foot: clinical science and offloading techniques.
AB  - Diabetic foot ulceration is a common, yet in many cases an eminently preventable,
      complication that affects 1 in 20 patients with diabetes. Risk factors for
      ulceration include insensitivity (secondary to somatic neuropathy), high foot
      pressures, callus formation (a consequence of sympathetic neuropathy and high
      foot pressures), deformities (such as claw feet, prominent metatarsal heads,
      etc.), peripheral vascular disease, and most importantly, a past history of
      ulceration. None of these factors alone causes ulceration; thus, early
      identification and amelioration of these factors is a primary aim in foot ulcer
      prevention. A number of therapeutic approaches may help reduce ulcer incidence:
      these include therapeutic footwear, hosiery, and, potentially, liquid silicone
      injected under high-pressure areas. In the management of neuropathic ulcers,
      pressure relief is of the utmost importance, and total contact casting remains
      the "gold standard" means of achieving such pressure redistribution. The
      successful management of diabetic foot ulceration depends on a team approach,
      remembering that ulcers should heal if (1) the arterial circulation is intact,
      (2) pressure relief is achieved and maintained over the ulcer, and (3) infection
      is appropriately treated.

PMID- 15147988
TI  - The use of antibiotics in the diabetic foot.
AB  - Lower limb infections are the most common indication for hospital admission in
      patients with diabetes. However, diagnosis of infection can be delayed because
      the normal clinical signs are often absent in patients with diabetes. The proper
      use of antibiotics in the treatment of the diabetic foot remains contested: one
      view is to administer antibiotics only in the presence of clinical infection; the
      other one is to give antibiotics freely to all patients with ulcers. This review
      of literature includes 2 controlled studies of antibiotics in diabetic foot
      ulcers. The first study showed no advantage from amoxicillin plus clavulanate as
      a supplement to standard therapy in uncomplicated ulcers. Patients (N = 44) with
      neuropathic ulcers (some of whom had cellulitis) were randomized to oral
      amoxicillin plus clavulanate or matched placebo. At 20 days' follow-up, there was
      no significant difference in outcome between the 2 groups. A further
      investigation (N = 64) compared ulcer patients who received oral antibiotics with
      those who did not. In the group with no antibiotics, 15 patients developed
      clinical infection, whereas none did in the antibiotic group (P <0.001). Seven
      patients in the nonantibiotic group needed hospital admission and 3 patients came
      to amputation. In the nonantibiotic group, 11 of 15 with infection had a positive
      swab compared with 1 of 17 without infection (P <0.01). In the nonantibiotic
      group, 17 patients healed, compared with 27 in the antibiotic group (P <0.02),
      with significantly more ischemic patients healing in the antibiotic group (P
      <0.01). Patients with diabetes who have clean ulcers associated with peripheral
      vascular disease and positive ulcer swabs should be considered for early
      antibiotic treatment. The diabetic foot is highly susceptible to repeat
      ulceration, and diabetic ulcers are more prone to infection than other ulcers.
      Furthermore, untreated infection can lead to amputation. This cycle can be broken
      only with aggressive treatment.

PMID- 15147989
TI  - Understanding experimental biology of skin equivalent: from laboratory to
      clinical use in patients with burns and chronic wounds.
AB  - A major breakthrough in burn wound care was the early excision of the burn and
      its immediate coverage with a skin autograft. A search for a skin-graft
      substitute began to reduce the autografting-related trauma at the donor site. One
      entry was skin equivalence, which contains 3 components: (1) living fibroblasts,
      suspended in (2) a native collagen matrix, the surface of which is covered with
      (3) viable keratinocytes. The tissue-cultured dermal fibroblasts are derived from
      human foreskin. The fibroblasts are grown in cell culture dishes as a monolayer
      and are retrieved by limited trypsin digestion. The fibroblast suspension is
      mixed with serum-supplemented culture medium and native acid-soluble collagen.
      The entire mixture, called a dermal equivalent, is placed in a bacteriological
      Petri dish before transfer to a 37 degrees C incubator. The collagen rapidly
      polymerizes, trapping cells in the dermal equivalent. During the initial 4 hours,
      fibroblasts elongate and spread, causing a decrease in the thickness of the
      dermal equivalent. After 6 hours, the dermal equivalent undergoes a decrease in
      diameter as a consequence of the reorganization of the collagen. A freshly
      isolated suspension of human skin-derived keratinocytes is seeded on the surface
      of a several-day-old floating dermal equivalent. The keratinocytes proliferate,
      covering the surface of the dermal equivalent. The keratinocytes deposit basement
      membranes beneath them and undergo epidermal cell differentiation, leading to the
      formation of a basal layer beneath differentiated cell layers. Both cell
      populations retain viability and release cell factors that have a positive effect
      on wound closure. The placement of skin equivalence within a chronic wound may
      share structural attributes with a skin graft, but its function is to accelerate
      closure.

PMID- 15147990
TI  - The role of surgical revascularization in the management of diabetic foot wounds.
AB  - Diabetic foot wounds affect an estimated 15% of all patients with diabetes. These
      wounds are typically multifactorial in origin. Neuropathy of the foot and
      impaired wound healing are frequently associated with peripheral arterial
      occlusive disease. These factors combine to contribute to the development of foot
      ulcers. Successful wound healing and limb salvage require prompt recognition and
      treatment. Assessment of arterial perfusion is imperative and may be accomplished
      by a combination of physical examination and noninvasive vascular laboratory
      studies. When associated with significant ischemia, diabetic foot ulcers require
      arterial revascularization to achieve wound healing.

PMID- 15147991
TI  - A specialized wound-healing center concept: importance of a multidisciplinary
      department structure and surgical treatment facilities in the treatment of
      chronic wounds.
AB  - The optimal way to improve prophylaxis and treatment of patients with problem
      wounds is to create an independent multidisciplinary wound-healing center that
      focuses on all types of problem wounds and has an outpatient clinic, as well as
      an inpatient ward. An integrated wound-healing department concept should be a
      standard in wound healing. A department structure containing both an outpatient
      clinic and inpatient ward, employing full-time personnel, allows the development
      of all features vital for optimal wound treatment. These are standardized
      treatment plans, access to relevant objective investigative methods and surgical
      approaches, a higher degree of continuity in treatment, increased patient
      satisfaction, greater potential for education and training, and improved
      possibilities for basic and clinical research in healing and care. The Copenhagen
      Wound Healing Center, Copenhagen, Denmark, and the University Center of Wound
      Healing, Odense, Denmark, are examples of this type of department. Initial
      results have demonstrated that these concept centers have resulted in improved
      rates of healing in patients with leg ulcers and have decreased the necessity for
      major amputations. The structure of the centers also offers greater opportunities
      for both basic and clinical research and provides expert education for all types
      of health care personnel. The centers were created in an attempt to establish an
      expert function in wound healing that would be fully integrated into the Danish
      national health care system. This model may, with individual modifications, be
      applicable for both industrialized and developing countries. In case it is
      impossible to realize the model in its entirety, alternative center concepts
      should be considered.

PMID- 15147992
TI  - Intractable wounds and infections: the role of impaired vascularity and advanced
      surgical methods for treatment.
AB  - Fracture nonunion, delayed union, and osteomyelitis remain serious problems with
      substantial morbidity and mortality rates. Healing promoters, including bone
      morphogenic proteins, fibroblast growth factors, and transforming growth factor
      beta, regulate bone growth in experimental models, such as those employing a
      "critical gap" to establish nonunion, but have not been effective in clinical
      situations. This paradox may relate to the fact that such agents target cells,
      yet in the setting of a clinical nonunion or osteomyelitis, the affected area is
      frequently hypovascular and therefore deficient in target precursor cells. Wound
      healing is dependent on local tissue vascularity. Surgical procedures, such as
      local and remote tissue transfer, which are designed to modify this cell
      deficient, poorly vascularized environment, have proved very successful but are
      often complex and costly. No simple pharmacologic means of upregulating such
      angiogenesis currently exists.

PMID- 15147993
TI  - Tissue and cellular approaches to wound repair.

PMID- 15147995
TI  - Debridement.
AB  - Debridement is defined as the removal of nonviable material, foreign bodies, and
      poorly healing tissue from a wound. Although surgeons recognize the importance of
      debridement, few data have been generated in randomized trials to support its
      use. Debridement provides for removal of tissue with the highest bacterial count,
      reliable cultures, and identification of osteomyelitis. The most direct form of
      debridement is surgical excision. For patients who are poor candidates for
      surgical debridement or have limited access to a surgeon, other forms of
      debridement (including mechanical, autolytic, enzymatic, and biologic) can be
      used. Although operative debridement is best performed by those with surgical
      training, the other forms of debridement can be accomplished by other allied
      health care professionals. Debridement remains an important adjunct to good wound
      care, but questions of what type, how much, and how often it should be performed
      remain unresolved.

PMID- 15147994
TI  - Understanding chronic wounds: a unifying hypothesis on their pathogenesis and
      implications for therapy.
AB  - The development of new therapies for treatment of chronic wounds has not matched
      the availability of treatment modalities forecast by the pharmaceutical industry.
      This is attributable in large part to difficulties encountered in clinical trials
      as well as in isolating study design variables. Our hypothesis attempts to
      address this shortcoming. We are proposing that chronic wound pathogenesis is
      based on 3 fundamental factors: the cellular and systemic changes of aging,
      repeated ischemia-reperfusion injury, and bacterial colonization with resulting
      inflammatory host response. The derivation of this hypothesis is founded on the
      observation that the 3 primary categories of chronic wounds--pressure ulcers,
      diabetic ulcers, and venous ulcers, which are the overwhelming majority of
      chronic wounds--have these common causative factors. Our hypothesis incorporates
      major implications for treatment modalities based on these factors. Addressing
      the first issue, the cellular and systemic changes of aging, Regranex (Ortho
      McNeil Pharmaceutical, Inc, Raritan, NJ), a platelet-derived growth factor drug,
      has shown great promise. Additional treatment modalities that address the second
      and third problems, repeated ischemia-reperfusion injury and bacterial
      colonization, include vacuum-assisted closure, warming of local tissue, and water
      irrigation using pulsed lavage. Additionally, treatment comprising a combination
      of these approaches has demonstrated success.

PMID- 15147996
TI  - Detailed protocol of ischemia and the use of noninvasive vascular laboratory
      testing in diabetic foot ulcers.
AB  - Diabetic foot ulcers are frequently complicated by the presence of arterial
      occlusive disease (PAD). It is often difficult to assess the severity of ischemia
      by history and physical examination alone; a combination of different types of
      noninvasive laboratory testing may be necessary. Pulse-volume recordings and
      segmental pressures should be routinely obtained. If questions persist, an
      anatomic study is warranted. Duplex ultrasonography can provide accurate
      information with little risk to the patient and so should be readily obtained.

PMID- 15147997
TI  - Complex reconstruction of the diabetic foot and ankle.
AB  - Reconstruction of the diabetic foot presents significant challenges for the
      surgeon. The goals of treatment are correction of deformity as well as
      elimination of infection, with production of a stable, plantigrade foot.
      Certainly not all patients with Charcot deformities require reconstruction. Many
      can be effectively managed with proper shoe modifications with orthoses. Bracing
      is also effective in providing support and in preventing further deformity.
      Surgical treatment is indicated for patients with recurrent ulceration or an
      unstable foot. Reconstruction of the Charcot foot should eliminate deformity and
      remove "high-pressure" areas of the foot and ankle. Achieving these goals should
      help prevent ulceration and infection, thereby avoiding the most devastating
      complication of the Charcot foot: amputation.

PMID- 15147998
TI  - Measurement of vigilance in 2-year-old children.
AB  - This study explored the behavioral manifestations of sustained attention in 2
      year-old children and the relation between sustained attention and its
      neurophysiological correlates. 51 children were administered a task of vigilance
      (the Early Childhood Vigilance Task; ECVT), along with behavioral measures of
      sustained attention that are routinely used as measures of attention in this age
      group. A subset of these children, n = 14, was also evaluated in an event-related
      potential (ERP) paradigm to identify patterns of neurophysiological activation
      that might be associated with sustained attention. The results supported the
      conceptualization of vigilance as a component of sustained attention that is
      related to, but distinct from, attention toward objects or activities with which
      one is actively engaged. Results also provided support for a specific association
      between vigilance and right frontal brain activity. Whereas ECVT performance was
      associated with ERP activation in the right frontal area, performance on more
      traditional behavioral measures of sustained attention was not.

PMID- 15147999
TI  - Developmental changes in real life decision making: performance on a gambling
      task previously shown to depend on the ventromedial prefrontal cortex.
AB  - Patients with bilateral lesions of the ventromedial prefrontal cortex, when
      performing gambling tasks modeling real-life decision-making, opt for choices
      that yield high immediate gains in spite of higher future losses. Under the
      hypothesis that the prefrontal cortex is the last brain region to mature, it was
      examined whether young children would show a similar preference for immediate
      prospects. In Experiment 1, 4 age groups (6-9, 10-12, 13-15 and 18-25 years olds)
      performed 2 versions of a computerized variant of the original Iowa gambling task
      under 3 different feedback conditions (no feedback, global feedback, and option
      specific feedback) and completed the Raven Standard Progressive Matrices as an
      index of inductive reasoning ability. In Experiment 2, 3 age groups (7-8, 11-12,
      and 15-16 year olds) performed both task versions in addition to a working memory
      task ("Digit Span Backwards"). Results showed a developmental increase in the
      sensitivity to future consequences, positive or negative, that could not be
      explained by developmental changes in working memory capacity or inductive
      reasoning. It was concluded that young children share with ventromedial
      prefrontal patients the failure to anticipate on future outcomes.

PMID- 15148000
TI  - Multimodal inhibition of return effects in adults with and without Down syndrome.
AB  - Data from a previous study (Welsh & Elliott, 2001) has been reanalyzed to explore
      inhibition of return (IOR) effects in adults with and without Down syndrome (DS).
      Participants were required to react and move with either the left or right hand
      as quickly as possible to 1 of 2 target locations based on either a visual or a
      verbal cue. Although persons with DS demonstrated a different pattern of
      information processing capabilities, they demonstrated the same magnitude of IOR
      across all conditions of presentation as their peers without DS. This pattern of
      results provides further support for the multimodal and response-based nature of
      IOR. Moreover, the results indicate that the inhibitory processes that underlie
      IOR in the average population seem to be functional in persons with DS.

PMID- 15148001
TI  - The use of online control: a developmental perspective.
AB  - To date very little research has addressed the abilities of young participants to
      respond to a change in visual information provided during movement execution.
      This study attempted to determine the ability of 45 participants (5, 7, 9 years)
      to respond to a change in visual information during a discrete rapid aiming
      movement. A perturbation paradigm where the target size changed after movement
      onset was used. In the control context, movements were made to each target size
      (small, medium, large) with no perturbation. In contrast, during the experimental
      context the target always began as a medium target. Upon movement initiation, the
      target size could remain constant or might unexpectedly become larger or smaller.
      Temporal, kinematic, and correction data were collected to determine the control
      process underlying the aiming movement. No interaction was found between age and
      condition for movement time (MT), and results indicated that all ages scaled
      movement time to final target size. The accuracy data revealed the 9-year-old
      participants were more accurate than the 5- and 7-year-old participants. To
      determine where the changes in duration were made, the time to and after peak
      velocity (TTPV, TAPV), and peak velocity values (PV) were examined. The PV values
      indicated that, during the control context, the participants scaled their
      movement to the target size. However, during the experimental condition generally
      no significant differences were found in either measure, suggesting a programmed
      response based on the original target size. This was supported by the correction
      data collected prior to peak velocity, lending further support to a programmed
      response. Following peak velocity, it was found that differences in MT were as a
      result of time spent in deceleration. This increased TAPV, and increased number
      of corrections observed, suggest that all participants were using on-line control
      following peak velocity in response to the change in visual information. The data
      collected supports a model of control that incorporates both open-loop control
      during the initial impulse phase, and closed-loop control during the current
      control phase for participants as young as 5 years.

PMID- 15148002
TI  - Psychophysical indexes of temporal processing abnormalities in children with
      developmental dyslexia.
AB  - Children with dyslexia and children progressing normally in reading performed
      several perceptual tasks to determine (a) the psychophysical measures that best
      differentiate children with dyslexia from children with average reading
      abilities; (b) the extent of temporal processing deficits in a single, well
      defined group of children with dyslexia; and (c) the co-occurrence of visual and
      auditory temporal processing deficits in children with dyslexia. 4 of our 12
      psychophysical tasks indicated differences in temporal processing ability between
      children with dyslexia and children with good reading skills. These included 2
      auditory tasks (dichotic pitch perception and FM tone discrimination) and 2
      visual tasks (global motion perception and contrast sensitivity). The battery of
      12 tasks successfully classified 80% of the children into their respective
      reading-level groups. Within the group of children with dyslexia who had temporal
      processing deficits, most were affected in either audition or vision; few
      children were affected in both modalities. The observed deficits suggest that
      impaired temporal processing in dyslexia is most evident on tasks that require
      the ability to synthesize local, temporally modulated inputs into a global
      percept and the ability to extract the resultant global percept from a noisy
      environment.

PMID- 15148003
TI  - Development of response-monitoring ERPs in 7- to 25-year-olds.
AB  - In a target discrimination task, trials with incorrect responses elicit event
      related potentials (ERPs) that include an error-related negativity (ERN or Ne)
      and a later error-positivity (Pe). Substantial evidence points to the anterior
      cingulate cortex as the source generator of the ERN. We examined the development
      of ERP component morphology, amplitude and latency to processing of correct and
      incorrect responses in 124 children, 7 to 18 years of age, and 27 adults, 19
      through 25 years of age. The ERN and Pe were recorded during a standard 480-trial
      visual flanker task. As expected, response times decreased significantly with
      age. The ERN amplitude in error trials increased with age, although this was
      qualified by a nonlinear change as well. The Pe amplitude did not change with
      age. In correct trials, most participants produced a small negativity
      corresponding to the timing of the ERN in error trials. This correct-response
      negativity (CRN) amplitude was larger in children than in adults. Results are
      discussed with respect to continued maturation of the anterior cingulate cortex
      and prefrontal cortex into young adulthood.

PMID- 15148005
TI  - Learning our patients' preferences is essential for optimal care.

PMID- 15148006
TI  - Treatment of terminal restlessness: a review of the evidence.
AB  - Terminal restlessness is an important issue in the management of symptoms at the
      end of life with between 25% and 88% of dying patients exhibiting this condition.
      (1-5) The purpose of this review was to examine the empiric evidence about the
      pharmacological treatment for terminal restlessness. All available literature, in
      all languages, from 1966-2002 including randomized trials, concurrent
      observations, retrospective chart reviews, single case studies, clinical practice
      guidelines, expert consensus, single expert opinion articles, and editorials were
      reviewed as "best available evidence." Of the 72 articles reviewed, 14 met the
      criteria and were chosen for analysis. Despite the majority of authors
      recommending neuroleptic medications as a first or second line pharmacological
      treatment of restlessness, a number of studies demonstrated the effectiveness of
      other medications such as benzodiazepines (notably midazolam and lorazepam), or
      phenothiazines, either alone or in combinations. There is insufficient evidence
      to suggest that a single medication or class of medications is appropriate for
      terminal restlessness. There is a clear need for additional trials of
      neuroleptics, benzodiazepines, barbiturates, and combination protocols to
      determine which protocols are the most effective and have the least side effects.

PMID- 15148007
TI  - Patterns of opioid analgesic prescription among patients with osteoarthritis.
AB  - This study describes patterns of opioid analgesic prescription during a one-year
      period among a sample of patients with osteoarthritis (OA). The study sample
      included 3,061 patients with prior ICD-9 codes indicating a diagnosis of OA who
      were treated at a federal Veterans Affairs Medical Center. Specific opioid
      variables included: any opioid prescription, number of specific opioid drugs
      prescribed, total number of opioid prescriptions, total number of days supply of
      opioids, and daily opioid doses. We also examined relationships of demographic
      characteristics to opioid variables. Results revealed that 41% of patients
      received at least one opioid prescription. Opioids were prescribed significantly
      less frequently among African-Americans than Caucasians and the number of opioid
      prescriptions declined with increasing age. The mean annual supply of opioids was
      104 days. Days' supply of opioids was also lower for African Americans and older
      patients. Daily opioid doses were, on average, below recommended daily doses for
      the treatment of OA. Findings of this study suggest that opioids are frequently
      prescribed to individuals with OA and that these drugs may be gaining
      acceptability for the treatment of chronic musculoskeletal pain. Additional
      research is needed to examine reasons for racial differences in opioid
      prescribing, as well as the prescription of these medications at fairly low
      doses.

PMID- 15148008
TI  - Knowledge and attitudes in pain management: Hong Kong nurses' perspective.
AB  - Effective pain management requires accurate knowledge, attitudes and assessment
      skills. To determine the current knowledge level and attitudes of nurses in pain
      management, 1,604 registered nurses working in three different hospitals in Hong
      Kong were invited to participate in this study. The sample consisted of 601
      registered nurses, 63 nursing officers, and 14 nursing specialists (N = 678). The
      response rate was 43%. The Nurses' Knowledge and Attitudes Survey Instrument
      questionnaire developed by McCaffery and Ferrell was translated into Chinese and
      used with permission. To ensure the contextual relevancy and consistency of the
      questionnaire, content validity and test-retest reliability tests were performed.
      The content validity index was 0.87 and the test-retest reliability (Spearman's p
      coefficient) was 0.812. The percentage of correctly answered questions was 44%.
      There was statistical significant in educational preparation and clinical
      experiences with correct scores. The findings of our study support the concern of
      inadequate knowledge and attitudes in relation to pain management. Further
      intensive continuing education and staff development is highly indicated for
      nurses in Hong Kong.

PMID- 15148009
TI  - Potent analgesics are more expensive for patients in developing countries: a
      comparative study.
AB  - Opioids are some of the most important analgesic medications for the management
      of both moderate to severe pain and several are included on the World Health
      organization (WHO) list of essential drugs. Opioid costs in developing countries
      have been reported to be higher than those in developed nations. This study
      documents retail prices and availability of several potent opioids in a number of
      developing and developed countries. Pain and Palliative Care specialists
      currently working in their countries were asked to collect data on the retail
      cost of a 30 day supply of 15 different opioid preparations in 5 developing and 7
      developed countries. Data were analyzed to compare costs and costs as a
      percentage of gross national product (GNP) per capita per month. Opioid costs and
      availability varied widely in both developing and developed countries. Forty five
      of 75 opioid preparations were available in developing countries (40% of
      medications studied were not available) and 76 of 105 preparations were available
      in the developed countries (28% not available). In US dollars, the median cost of
      opioids differed between developed and developing countries ($53 and $112
      respectively) The median costs of all opioid preparations as a percentage of GNP
      per capita per month were 36% for developing and 3% for developed nations; the
      difference was statistically significant (p < 0.001). In developing countries 23
      of 45 (51%) of opioid dosage forms cost more than 30% of the monthly GNP per
      capita, versus only three of 76 (4%) in developed countries. The relative cost of
      opioids to income is higher in developing countries. Our data suggest that in
      developing countries opioid access for the majority of patients is likely to be
      limited by cost, and development of palliative care programs will require heavy
      or total subsidization of opioid costs.

PMID- 15148010
TI  - The ethics of end-of-life research.
AB  - A notable and welcome increase in palliative care research has led to a multitude
      of ethical issues and concerns for researchers, clinicians, patients (subjects)
      and their family members (who also might be subjects), granting agencies, and
      professional journals. This edition of "Palliative Care Pearls" summarizes the
      recommendations from a work group that met at the National Institutes of Health
      in September, 2002. The primary purpose for that meeting was to explore the
      unique characteristics of this research population and the ethical concerns that
      might require tailoring of "standard" clinical research processes. The
      proceedings culminated in a document from which open discourse and a more formal
      set of guidelines might emanate to both foster more and better research, while
      providing protections for research subjects. This 62 page long monograph was
      published as a supplement to the Journal of Pain and Symptom Management (April,
      2003). It includes six "plenary" papers, each that focuses on a distinct ethical
      domain of palliative care research and concludes with a set of recommendations
      and research questions. These might best be viewed as hypotheses that need to be
      tested or further explored.

PMID- 15148011
TI  - Evidence-based pain management and palliative care in The Cochrane Library.
AB  - The Cochrane Library of systematic reviews is published quarterly. Issue 2 for
      2003 of the library was published in May 2003. That issue contains 2395 reviews
      of which 1669 are in full text. The issue contains 79 new reviews, seven of those
      are directly relevant to pain management and palliative care. Annotated
      bibliographies for those seven reviews are provided. Issue 3 for 2003, published
      in July 2003, contains 3058 reviews and protocols of which 1754 are fully
      published reviews. Issue 3 contains 85 new reviews, five are relevant to
      practitioners in pain and palliative care. References are published in the same
      format as the citation for Cochrane reviews. The Cochrane trials database now
      stands at over 375,000 records with an additional 4100 one-page summaries of non
      Cochrane reviews in the NHS database of reviews of effectiveness (DARE).

PMID- 15148012
TI  - Advance care planning: preferences for care at the end of life.
AB  - Predictors of patient wishes and influence of family and clinicians are
      discussed. Research findings on patient decision-making relating to preferences
      in end-of-life care are described. Advance directives and durable powers of
      attorney are defined and differentiated. Most patients have not participated in
      advance care planning and the need for more effective planning is documented.
      Appropriate times for discussions of such planning are described. Scenarios
      discussed include terminal cancer, chronic obstructive pulmonary disease, AIDS,
      stroke, and dementia. Patient satisfaction is discussed, as is a structured
      process for discussions about patient preferences. Results of patient responses
      to hypothetical scenarios are described. Invasiveness of interventions, prognosis
      and other factors that favor or discourage patient preferences for treatment are
      discussed. Findings resulting from research funded by the Agency for Healthcare
      Research and Quality (AHRQ) are discussed. This research can help providers offer
      end-of-life care based on preferences held by the majority of patients under
      similar circumstances.

PMID- 15148015
TI  - Sources of information on postgraduate medical training programs - 2004 update.
AB  - This is the biennial update listing directories, journal articles, Web sites, and
      general books that aid the librarian, house officer, or medical student in
      finding information on medical residency and fellowship programs. The World Wide
      Web provides the most current and complete source of information about
      postgraduate training programs and specialties. This update goes beyond
      postgraduate training resources to include selected Web sites and books on resume
      writing, practice management, personal financial issues, the "Match," exam
      preparation, job hunting, and the DEA license application process. Print
      resources are included if they provide information not on the Internet or have
      features that are particularly useful. The Internet continues to be a major
      marketing tool for hospitals seeking to recruit the best and brightest for their
      residency and fellowship programs. Even the smallest community hospital usually
      has a presence on the 'Net.

PMID- 15148016
TI  - Evaluation of evidence-based medicine search skills in the clinical years.
AB  - The librarians of the Health Sciences Library worked with the director of the
      Primary Care Clerkship to reinforce the principles of Evidence-Based Medicine
      (EBM) searching, taught during the first two years of medical school, through an
      intensive workshop. The purpose of the program was to ensure that students apply
      EBM principles in a timely and effective manner in clinical situations. Working
      in teams led by a resident and librarian, students researched real cases and then
      evaluated the effectiveness of their approach to the problems. This paper
      outlines the rationale for the team approach, reviews the administration of a
      computer-based workshop, and discusses the evaluation process. Evaluation focused
      on both the current workshop and its implications for the informatics program
      presented to students during years one and two.

PMID- 15148017
TI  - Assessing reference staff competency in the electronic environment.
AB  - This paper shows how the Galter Health Sciences Library of Northwestern
      University's Feinberg School of Medicine developed and implemented a program to
      assess reference staff competencies for assisting users in the electronic
      environment after completing a new training program. The first phase was a year
      long assessment of reference questions to identify the types of questions
      received at the desk. Next, a training program for reference was developed and
      implemented with an emphasis on answering the most common questions identified
      such as remote access, access privileges, holdings information, and database
      searching. The program included individualized instruction on library policies,
      electronic resources, access restrictions, and troubleshooting. The next phase
      was to create instruments to test staff competencies in answering questions after
      training. Based on the scores, additional training was individualized and
      provided to the appropriate staff member to enhance their skills where needed.
      The training system that was developed has proven to be effective as most staff
      scored better than 92% on initial testing. As a result, library management can be
      certain that users' questions are being answered correctly and that the staff has
      the skills required to work in an electronic environment.

PMID- 15148018
TI  - Portable classroom leads to partnership.
AB  - Library faculty participation on the School of Medicine Curriculum Steering
      Committee led to a unique opportunity to partner technology and teaching
      utilizing the library's portable wireless classroom. The pathology lab course
      master expressed a desire to revise the curriculum using patient cases and direct
      access to the Web and library resources. Since the pathology lab lacked
      computers, the library's portable wireless classroom provided a solution.
      Originally developed to provide maximum portability and flexibility, the wireless
      classroom consists of ten laptop computers configured with wireless cards and an
      access point. While the portable wireless classroom led to a partnership with the
      School of Medicine, there were additional benefits and positive consequences for
      the library.

PMID- 15148019
TI  - Haz-Map: information on hazardous chemicals and occupational diseases.
AB  - Haz-Map is a newWeb-based information resource, available on the National Library
      of Medicine's TOXNET system. It contains information on the epidemiology of
      occupational or job task related diseases. Haz-Map also provides links to
      information about industrial hygiene related to occupational exposure to a
      specific list of toxic chemicals. Background information, search hints, and a
      content description of Haz-Map are provided.

PMID- 15148020
TI  - Spirituality and health care: Internet resources.
AB  - Medicine and spirituality have had an enduring, complementary relationship from
      the earliest days of health care. Recent publications, Web site developments, and
      education programs underscore the continuing enthusiasm for the study of the
      relationship between spirituality and patient care in the health care community.
      This article outlines a selective list of Internet sites and online resources and
      serves as a guide for further inquiry into spirituality and health care concepts.

PMID- 15148021
TI  - Education for inpatients: working with nurses through the clinical information
      system.
AB  - Librarians at the UMDNJ Cooper Library have been filling orders for patient
      education materials through Cooper University Hospital's Clinical Information
      System (CIS) since December 2000. This service was instituted in response to a
      JCAHO survey, which revealed that although patient education was being provided,
      it was not being routinely documented. Patient education orders fall into two
      categories: customized disease/procedure information and smoking cessation
      information. Nurses note the condition(s) and/or procedure(s) regarding which
      information is needed and indicate the education level of the material desired
      (basic, intermediate or advanced). Requests are received via a dedicated printer
      in the reference office. Librarians rely heavily upon a wide variety of Web-based
      consumer health resources, including proprietary resources such as MD Consult and
      Micromedex CareNotes. Patient Transport staff delivers two copies of all
      materials to nursing stations on patient care floors. One copy is for the patient
      to keep, while the other is attached to the patient's chart. To complete and
      document that patient education was provided, librarians record the order as
      filled in the CIS system.

PMID- 15148022
TI  - Millennials in action: a student-guided effort in curriculum-integration of
      library skills.
AB  - By working in tandem with the Coordinator of Information Management Education
      (IME) at the University at Buffalo Health Sciences Library, students serving on
      the School of Pharmacy and Pharmaceutical Sciences Curriculum Committee helped
      map out a three-year plan for training in library and information literacy
      skills. Through meetings and e-mail exchanges with the student representatives,
      the IME Coordinator developed a series of specific course-related instruction and
      assessment opportunities which would cover tertiary resources, bibliographic
      searching, evidence-based pharmacy, and advanced information skills.

PMID- 15148042
TI  - Retirement financial preparation:implications for policy.
AB  - Financial preparation for retirement is key to positive outcomes for future
      cohorts. Studies suggest that insufficient preparation is occurring among Baby
      Boomers. Data from community-dwelling adults (N = 1508, ages 40-70) show that
      most respondents (22-75%) had taken four specific preparation steps, and few
      reported negative attitudes toward planning. Five correlates (gathering
      information, locus of control, self-definition as household planner, financial
      worries, and negative attitudes) and demographic variables tested in bivariate
      analyses showed most having associations with preparation. In multivariate
      analyses, however, only two correlates (gathering information and negative
      planning attitudes) and demographics (race/ethnicity, education, income, health,
      age, and education) explained planning behavior.

PMID- 15148041
TI  - The multiple dimensions of individual financial preparation for long-term care.

PMID- 15148043
TI  - Long-term care planning as a cultural system.
AB  - This paper treats long-term care planning from a cultural perspective, that is,
      as a cultural system in which components of long-term care interlock culturally
      and therefore meaningfully. In the introduction and background sections, we
      provide a context in which long-term care planning may be viewed, based on the
      finding that relatively few people take advantage of long-term care planning and
      insurance; we also discuss some earlier work on long-term care from a
      psychological perspective that emphasizes themes of imagination and self
      efficacy. We then examine long-term care from a cultural perspective by
      identifying and explicating five broad themes that help us better understand the
      meaning of long-term care planning to Americans. Finally, we use these themes to
      suggest some important social policy correlates.

PMID- 15148044
TI  - Preferences for receipt of care among community-dwelling adults.
AB  - Preferences for long-term care alternatives include both place of care and
      persons to provide care. In this analysis, these elements are separated for
      mature adults (N-1503, ages 40-70) regarding future care needs. Most adults
      preferred care in home/community settings by kin or non-kin, with few deeming
      nursing homes acceptable. Demographics and personal knowledge, experience, and
      expectations were marginally likely to influence preferences; males were more
      likely to prefer care in paid/professional settings. Women, who more often
      expressed preference for kin/home care, face demographic trends reducing
      available female kin who might be caregivers.

PMID- 15148045
TI  - The importance of employer sponsorship in the long-term care insurance market.
AB  - Medicare and Medicaid are major sources of long-term care payments and thus will
      bear much of the burden from the growth in long-term care service use. The large
      future demand for long-term care services is of great concern among policymakers
      due to its expense and the use of public program dollars. It is argued that the
      individual purchase of long-term care insurance can help alleviate the increasing
      financial pressure on public programs responsible for the majority of longterm
      care financing. However, consumers have shown little interest in insuring against
      the high costs of long-term care. This analysis examines the effect of several
      factors on the decision to purchase a long-term care insurance policy: knowledge
      and attitudes of long-term care insurance and the long-term care financing
      system, the perceived risk for longterm care, financial planning behavior, and
      the availability of long-term care insurance. The interim results indicate the
      factor most likely to affect the decision to purchase long-term care insurance is
      access to employer-sponsored long-term care insurance. This suggests tht the
      availability of affordable and high quality coverage is more important than
      demand-side factors such as awareness of long-term care insurance and a perceived
      greater risk for long-term care.

PMID- 15148046
TI  - Convergence of long-term care planning and retirement planning at the work place.
AB  - There is an increasing expectation that the private-sector should provide needed
      solutions to pressing problems in long-term care. Long-term care insurance has
      figured prominently in recent discussions. Within the long-term care insurance
      market, the potential of the employer in making such insurance available to
      employees has been discussed extensively. This paper traces the increasing
      convergence of retirement planning and long-term care planning at the work place.
      The long-term care insurance market has come a long way, and the employer
      sponsored segment of the market has recorded the highest rate of growth in recent
      times. Furthermore, the employer-sponsored market is beginning to diversify. Low
      take-up rates still remain a problem. Recent rapid growth of the market coupled
      with the federal government's involvement as an employer offering long-term care
      insurance is bound to expand the market further.

PMID- 15148047
TI  - Comparison of dementia-specific quality of life measures in adult day centers.
AB  - This study evaluated five dementia-specific quality of life (DQOL) measures
      including client interviews, staff proxies, and observations with 54 clients in
      three adult day centers. Also, the relationship of cognitive and functional
      status to each of the DQOL measures was assessed. Client interviews correlated
      well with each other, but not with other measures. Staff proxies were strongly
      correlated with each other and moderately correlated with the observational
      measure. On average, clients rated their DQOL higher than staff. Analyses suggest
      that functional impairment is associated with poorer DQOL as indicated by staff
      and observer measures. Possible explanations and implications are explored.

PMID- 15148048
TI  - Home care before and after hospitalization for acute myocardial infarction in
      Alberta, Canada.
AB  - Home care services are provided to about 10% of those admitted to hospital for
      acute myocardial infarction and about 20% of those discharged from hospital. The
      use of home care in patients with an acute myocardial infarction is growing in
      Alberta over the brief time span of this four year study. Those that received
      home care prior to a hospitalization for acute myocardial infarction were "old
      and frail" with a high mortality rate during and after hospitalization. The
      provision of home care after hospitalization selected those patients that stay in
      hospital longer and required more hospital care. BACKGROUND: The use of home care
      before and after hospitalization for acute myocardial infarction is described.
      METHODS: Hospital discharge abstracts were used to identify patients hospitalized
      in alberta, canada for acute myocardial infarction which were then linked to home
      care administrative data. RESULTS: There were 12,648 patients with acute
      myocardial infarction from April 1, 1995 until March 31, 1999. Home care within
      60 days prior to hospitalization was provided for 8.7% of patients with acute
      myocardial infarctions (n = 1097) which significantly (p = 0.023) increased from
      7.6% in the fiscal year 1995/6 to 9.5% in the fiscal year 1998/9. Home care
      within 60 days after hospitalization was provided to 16.4% of patients with acute
      myocardial infarctions (n = 2076) which significantly (p < 0.000) increased from
      14.1% in the fiscal year 1995/6 to 18.1% in fiscal year 1998/9. Recipients of
      home care were significantly older, had more comorbidities, and greater severity
      of illness, but were less likely to undergo coronary artery revascularization
      during hospitalization. After multivariate adjustment, length of hospital stay,
      60 day re-admissions, and mortality were higher in those receiving home care post
      hospitalization. Nearly half of those receiving home care prior to
      hospitalization died within one year. 80% of those receiving home care prior to
      admission also received home care services after hospitalization. CONCLUSION:
      Those patients who received home care prior to a hospitalization for acute
      myocardial infarction were "old and frail" with a high mortality rate during and
      after hospitalization. The provision of home care after hospitalization selected
      those patients that stay in hospital longer and required more hospital care.

PMID- 15148049
TI  - Does payment structure influence change in physical functioning after
      rehabilitation therapy?
AB  - PURPOSE: To determine if there are differences by payment structure (Medicare
      managed care versus fee-for-service) in the duration and intensity of geriatric
      rehabilitation therapy treatments and measure their effect on change in physical
      functioning at discharge. METHODS: Sixty-eight Medicare managed care (MCO) and 32
      fee-for-service (FFS) subjects from 3 skilled nursing facilities (SNFs) in
      Southern California answered the physical functioning dimension of the Sickness
      Impact Profile (SIP-PFD) before and after rehabilitation therapy. Patient
      characteristics at admission, therapy treatments, and discharge physical
      functioning were compared by payment structure using chi-square and t-tests;
      logistic and ordinary least squares (OLS) regressions were employed to determine
      significant predictors of enrollment in managed care and change in physical
      functioning at discharge. RESULTS: Payment structure yielded no significant
      differences in patient characteristics (physical functioning, socio-demographics,
      and clinical characteristics) at admission to rehabilitation. Compared to MCO
      subjects, FFS subjects received significantly more minutes per day (intensity) of
      rehabilitation therapy (Mean difference = - 16.90; t-test = - 4.504; p =.000). On
      average, all subjects reported significant, positive change in physical
      functioning from admission to discharge after rehabilitation (Mean change = 7.98,
      SD = 12.96; t-test = 6.157; p =.000); but change in physical functioning between
      MCO and FFS subjects was not significant. CONCLUSIONS: Payment structure did not
      significantly influence change in physical functioning at discharge. Future
      studies, using a larger sample- size, should consider the effects of structural
      elements, process, and patient behavior on therapy treatments and physical
      functioning outcomes.

PMID- 15148050
TI  - Occupational exposure to diesel exhaust fumes.
AB  - There is currently no OEL for diesel fumes in the UK. This study reports parallel
      measurements of airborne levels of diesel fume pollutants in nine distribution
      depots where diesel powered fork-lift trucks (FLTs) were in use. Correlations
      between individual pollutants are assessed as well as their spatial distribution.
      Samples were collected on board FLTs and at background positions at nine
      distribution depots. Substances measured and the range of exposures by site were:
      respirable dust (n = 76) GM </= 80-179 micro g/m(3); elemental carbon (n = 79) GM
      = 7-55 micro g/m(3); organic carbon (n = 79) GM = 11-69 micro g/m(3); ultrafine
      particles (n = 17) range = 58-231 x 10(3) particles/cm(3); selected particulate
      phase polycyclic aromatic hydrocarbons (PAHs) (n = 14) range = 6-37 ng/m(3). In
      addition, a tracer method based on ultrafine particle measurements was used to
      estimate the spatial distribution of total carbon and PAHs at the sites
      monitored. The spatial distribution was found to be reasonably uniform. Major
      diesel fume aerosol components were, in general, well correlated (r = 0.62-0.97).
      CO(2) measurements were also made and found to be below the HSE guideline of 1000
      p.p.m., with most levels below 600 p.p.m.

PMID- 15148051
TI  - Occupational exposure to dioxins at UK worksites.
AB  - Following a request from a Governmental Interdepartmental Group, the Health and
      Safety Executive undertook a polychlorinated dibenzo-p-dioxin (PCDD) and
      polychorinated dibenzofuran (PCDF) sampling exercise at several work sites in the
      UK. An initial survey suggested potential PCDD/F production at metal recycling
      sites, during cement manufacture, at municipal waste incinerators and landfill
      sites and during the use of thermal oxygen lances. PCDD/F sampling, using static
      and personal air samplers, revealed that the highest PCDD/F exposures were found
      at metal recycling sites, particularly aluminium recycling sites. The reasons for
      these results and the possible consequential intakes are discussed.

PMID- 15148052
TI  - Determinants of isocyanate exposures in auto body repair and refinishing shops.
AB  - As part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY),
      the determinants of isocyanate exposure in auto body repair shops were evaluated.
      Measurements (n = 380) of hexamethylene diisocyanate-based monomer and
      polyisocyanate and isophorone diisocyanate-based polyisocyanate were collected
      from 33 auto body shops. The median total reactive isocyanate concentrations
      expressed as mass concentration of the NCO functional group were: 206 microg
      NCO/m3 for spray operations; 0.93 microg NCO/m3 for samples collected in the
      vicinity of spray operations done on the shop floor (near spray); 0.05 microg
      NCO/m3 for office or other shop areas adjacent to spray areas (workplace
      background); 0.17 microg NCO/m3 for paint mixing and gun cleaning operations
      (mixing); 0.27 microg NCO/m3 for sanding operations. Exposure determinants for
      the sample NCO mass load were identified using linear regression, tobit
      regression and logistic regression models. For spray samples in a spray booth the
      significant determinants were the number of milliliters of NCO applied, the
      gallons of clear coat used by the shop each month and the type of spray booth
      used (custom built crossdraft, prefabricated crossdraft or downdraft/semi
      downdraft). For near spray (bystander) samples, outdoor temperature >65 degrees F
      (18 degrees C) and shop size >5000 feet2 (465 m2) were significant determinants
      of exposure levels. For workplace background samples the shop annual income was
      the most important determinant. For sanding samples, the shop annual income and
      outdoor temperature >65 degrees F (18 degrees C) were the most significant
      determinants. Identification of these key exposure determinants will be useful in
      targeting exposure evaluation and control efforts to reduce isocyanate exposures.

PMID- 15148053
TI  - Mesothelioma and lung cancer among motor vehicle mechanics: a meta-analysis.
AB  - We conducted a systematic review and analysis of the epidemiological literature
      that examines the risk of lung cancer and mesothelioma among motor vehicle
      mechanics who may have been engaged in brake repair and, thus, were potentially
      exposed to asbestos. All relevant studies were classified into three tiers
      according to their quality. Tier III (lowest quality) studies were cited for
      completeness, but were not included in the meta-analysis. Meta relative risks
      (meta-RRs) were calculated for mesothelioma and lung cancer using both fixed and
      random effects models for Tiers I and II, separately, followed by stratified
      analyses based on study design or exposure characterization (garage workers
      versus brake workers) and, for lung cancer studies, based on adequate adjustment
      for smoking. The meta-analysis for Tier I (higher quality) and Tier II (lower
      quality) studies of mesothelioma yielded RR estimates of 0.92 (95% CI 0.55-1.56)
      and 0.81 (95% CI 0.52-1.28), respectively. Further stratification according to
      exposure characterization did not affect the results. The meta-analysis for lung
      cancer produced RR estimates of 1.07 (95% CI 0.88-1.31) for Tier I and 1.17 (95%
      CI 1.01-1.36) for Tier II. When the lung cancer analysis was limited to studies
      that used adequate control for smoking, the resulting RR estimate was 1.09 (95%
      CI 0.92-1.28). Based on these findings, we conclude that employment as a motor
      vehicle mechanic does not increase the risk of developing mesothelioma. Although
      some studies showed a small increase in risk of lung cancer among motor vehicle
      mechanics, the data on balance do not support a conclusion that lung cancer risk
      in this occupational group is related to asbestos exposure.

PMID- 15148054
TI  - British occupational hygiene practice 1720-1920.
AB  - The first recognition of the profession of occupational hygienist was preceded by
      at least 200 years of developments in disease prevention practices in the
      workplace, many of which could readily be characterized as occupational hygiene.
      The nature and pace of adoption of these practices depended on the contemporary
      state of technology, science, medicine and social concern. At first it was a
      matter of individual initiative and did not depend on quantitative data, but by
      the second half of the 19th century techniques of measurement for both harmful
      effects and for exposure were being introduced and official bodies at both
      national and local level were active. People from a wide range of backgrounds
      made contributions to disease prevention at work and by 1920 most of the major
      concepts and practices of current occupational hygiene practice were in place, if
      only in rather limited settings.

PMID- 15148055
TI  - Characterization of embryonic cardiac pacemaker and atrioventricular conduction
      physiology in Xenopus laevis using noninvasive imaging.
AB  - Congenital heart defects often include altered conduction as well as
      morphological changes. Model organisms, like the frog Xenopus laevis, offer
      practical advantages for the study of congenital heart disease. X. laevis embryos
      are easily obtained free living, and the developing heart is readily visualized.
      Functional and morphological evidence for a conduction system is available for
      adult frog hearts, but information on the normal properties of embryonic heart
      contraction is lacking, especially in intact animals. With the use of fine glass
      microelectrodes, we were able to obtain cardiac recordings and make standard
      electrophysiological measurements in 1-wk-old embryos (stage 46). In addition, a
      system using digital analysis of video images was adapted for measurement of the
      standard cardiac intervals and compared with invasive measurements. Video images
      were obtained of the heart in live, pharmacologically paralyzed, stage 46 X.
      laevis embryos. Normal values for the timing of the cardiac cycle were
      established. Intervals determined by video analysis (n = 53), including the
      atrial and ventricular cycle lengths (473 +/- 10 ms and 464 +/- 19 ms,
      respectively) and the atrioventricular interval (169 +/- 5 ms) were not
      statistically different from those determined by intrathoracic cardiac
      recordings. We also present the data obtained from embryos treated with standard
      medications that affect the human conduction system. We conclude that the
      physiology of embryonic X. laevis cardiac conduction can be noninvasively studied
      by using digital video imaging. Additionally, we show the response of X. laevis
      embryonic hearts to chronotropic agents is similar but not identical to the
      response of the human heart.

PMID- 15148056
TI  - Remodeling of the chronic severely failing ischemic sheep heart after coronary
      microembolization: functional, energetic, structural, and cellular responses.
AB  - The mandatory use of pharmacotherapy in human heart failure (HF) impedes further
      study of natural history and remodeling mechanisms. We created a sheep model of
      chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35%
      stable over 4 wk] by selective coronary microembolization under general
      anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and
      cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58%
      success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for
      analysis) after the LVEF stabilized (median of 3 embolizations). Early doubling
      of LV end-diastolic pressure persisted, as did increases in LV end-diastolic
      volume, LV wall stress, and LV wall thinning. Contractile impairment (LV end
      systolic elastance, LV preload recruitable stroke work, and dobutamine-responsive
      contractile reserve) and diastolic dysfunction also remained stable. Cardiac
      mechanical energy efficiency did not recover. Plasma atrial natriuretic peptide
      levels remained elevated, but rises in plasma aldosterone and renin activity were
      transient. Collagen content increased 170%, the type I-to-III phenotype ratio
      doubled in the LV, but right ventricular collagen remained unaltered. Fas ligand
      cytokine levels correlated with expression of both caspase-3 and -2, suggesting a
      link in the apoptotic "death cascade." Caspase-3 activity also bore a close
      relationship to LV meridional wall stress calculated from echocardiographic and
      intraventricular pressure measurements. We concluded that the stability of
      chronic untreated severe ischemic HF depends on the recruitment of myocardial
      remodeling mechanisms that involve an interaction among hemodynamic load,
      contractile efficiency/energetics, neurohumoral activation, response of the
      extracellular matrix, wall stress, and the myocyte apoptotic pathway.

PMID- 15148057
TI  - Acute myocardial infarction induces hypothalamic cytokine synthesis.
AB  - The inflammatory milieu of acute myocardial infarction (MI) is theoretically
      conducive to enhanced cytokine synthesis within the brain. We tested the
      hypothesis that synthesis of tumor necrosis factor-alpha (TNF-alpha), an
      indicator of proinflammatory cytokine activity, increases in brain after MI. MI
      was induced in rats by ligating the left anterior descending coronary artery and
      confirmed by echocardiography. Plasma and tissue levels of TNF-alpha were
      measured using ELISA; TNF-alpha mRNA was measured with real-time PCR. Heart,
      brain, and plasma samples were obtained 0.5, 1, 4, or 24 h or 4 wk after MI. TNF
      alpha synthesis increased in the brain, heart, and plasma within minutes to hours
      after MI and was sustained over the interval tested. Among the brain tissues
      examined, TNF-alpha increased selectively in hypothalamus. Chronic treatment with
      pentoxifylline prevented the increases in TNF-alpha in brain, heart, and plasma
      measured 4 wk after MI. MI-induced cytokine synthesis in the hypothalamus and its
      prevention by pentoxifylline have important implications in the context of the
      development of heart failure after MI.

PMID- 15148058
TI  - In vivo role of heme oxygenase in ischemic coronary vasodilation.
AB  - The heart constitutively expresses heme oxygenase (HO)-2, which catabolizes heme
      containing proteins to produce biliverdin and carbon monoxide (CO). The heart
      also contains many possible substrates for HO-2 such as heme groups of myoglobin
      and cytochrome P-450s, which potentially could be metabolized into CO. As a
      result of observations that CO activates guanylyl cyclase and induces vascular
      relaxation and that HO appears to confer protection from ischemic injury, we
      hypothesized that the HO-CO pathway is involved in ischemic vasodilation in the
      coronary microcirculation. Responses of epicardial coronary arterioles to
      ischemia (perfusion pressure approximately 40 mmHg; flow velocity decreased by
      approximately 50%; dL/dt reduced by approximately 60%) were measured using
      stroboscopic fluorescence microangiography in 34 open-chest anesthetized dogs.
      Ischemia caused vasodilation of coronary arterioles by 36 +/- 6%. Administration
      of N(G)-monomethyl-L-arginine (L-NMMA, 3 micromol.kg(-1).min(-1) intracoronary),
      indomethacin (10 mg/kg iv), and K(+) (60 mM, epicardial suffusion) to prevent the
      actions of nitric oxide, prostaglandins, and hyperpolarizing factors,
      respectively, partially inhibited dilation during ischemia (36 +/- 6 vs. 15 +/-
      4%; P < 0.05). The residual vasodilation during ischemia after antagonist
      administration was inhibited by tin mesoporphyrin IX (SnMP, 10 mg/kg iv), which
      is an inhibitor of HO (15 +/- 4 vs. 7 +/- 2%; P < 0.05 vs. before SnMP). The
      guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10(-5) M,
      epicardial suffusion) also inhibited vasodilation during ischemia in the presence
      of L-NMMA with indomethacin and KCl. Moreover, administration of heme-L-arginate,
      which is a substrate for HO, produced dilation after ischemia but not after
      control conditions. We conclude that during myocardial ischemia, HO-2 activation
      can produce cGMP-mediated vasodilation presumably via the production of CO. This
      vasodilatory pathway appears to play a backup role and is activated only when
      other mechanisms of vasodilation during ischemia are exhausted.

PMID- 15148059
TI  - Comparative analysis of parvalbumin and SERCA2a cardiac myocyte gene transfer in
      a large animal model of diastolic dysfunction.
AB  - Diastolic dysfunction results from impaired ventricular relaxation and is an
      important component of human heart failure. Genetic modification of intracellular
      calcium-handling proteins may hold promise to redress diastolic dysfunction;
      however, it is unclear whether other important aspects of myocyte function would
      be compromised by this approach. Accordingly, a large animal model of humanlike
      diastolic dysfunction was established through 1 yr of left ventricular (LV)
      pressure overload by descending thoracic aortic coarctation in canines. Serial
      echocardiography documented a progressive increase in LV mass. Diastolic
      dysfunction with preserved systolic function was evident at the whole organ and
      myocyte levels in this model, as determined by hemispheric sonomicrometric
      piezoelectric crystals, pressure transducer catheterization, and isolated myocyte
      studies. Gene transfer of the sarco(endo)plasmic reticulum calcium-ATPase
      (SERCA2a) and parvalbumin (Parv), a fast-twitch skeletal muscle Ca(2+) buffer,
      restored cardiac myocyte relaxation in a dose-dependent manner under baseline
      conditions. At high Parv concentrations, sarcomere shortening was depressed. In
      contrast, during beta-adrenergic stimulation, the expected enhancement of myocyte
      contraction (inotropy) was abrogated by SERCA2a but not by Parv. The mechanism of
      this effect is unknown, but it could relate to the uncoupling of
      SERCA2a/phospholamban in SERCA2a myocytes. Considering that inotropy is vital to
      overall cardiac performance, the divergent effects of SERCA2a and Parv reported
      here could impact potential therapeutic strategies for human heart failure.

PMID- 15148060
TI  - Distribution of stress and strain along the porcine aorta and coronary arterial
      tree.
AB  - The existence of a homeostatic state of stresses and strains has been axiomatic
      in the cardiovascular system. The objective of this study was to determine the
      distribution of circumferential stress and strain along the aorta and throughout
      the coronary arterial tree to test this hypothesis. Silicone elastomer was
      perfused through the porcine aorta and coronary arterial tree to cast the
      arteries at physiological pressure. The loaded and zero-stress dimensions of the
      vessels were measured. The aorta (1.8 cm) and its secondary branches were
      considered down to 1.5 mm diameter. The left anterior descending artery (4.5 mm)
      and its branches down to 10 microm were also measured. The Cauchy mean
      circumferential stress and midwall stretch ratio were calculated. Our results
      show that the stretch ratio and Cauchy stress were lower in the thoracic than in
      the abdominal aorta and its secondary branches. The opening angle (theta) and
      midwall stretch ratio (lambda) showed a linear variation with order number (n) as
      follows: theta = 10.2n + 63.4 (R(2) = 0.989) and lambda = 4.47 x 10(-2)n + 1.1
      (R(2) = 0.995). Finally, the stretch ratio and stress varied between 1.2 and 1.6
      and between 10 and 150 kPa, respectively, along the aorta and left anterior
      descending arterial tree. The relative uniformity of strain (50% variation) from
      the proximal aorta to a 10-microm arteriole implies that the vascular system
      closely regulates the degree of deformation. This suggests a homeostasis of
      strain in the cardiovascular system, which has important implications for
      mechanotransduction and for vascular growth and remodeling.

PMID- 15148061
TI  - Transmembrane action potential heterogeneity in the canine isolated arterially
      perfused right atrium: effect of IKr and IKur/Ito block.
AB  - The role of electrical heterogeneity in development of cardiac arrhythmias is
      well recognized. The extent to which transmembrane action potential (TAP)
      heterogeneity contributes to the normal electrophysiology of well-oxygenated
      atria is not well defined. The principal objective of the present study was to
      define regional and transmural differences in characteristics of the TAP in
      isolated superfused and arterially perfused canine right atrial (RA) preparations
      under baseline, rapidly activating delayed rectifier K(+) current (I(Kr)) block,
      and combined block of ultrarapid delayed rectifier and transient outward K(+)
      current (I(Kur)/I(to) block). Superfused preparations that survived generally
      displayed a triangle-shaped TAP. Exceptions included cells from the crista
      terminalis, where TAPs with a normal plateau could be recorded. In contrast, most
      TAPs recorded from throughout the perfused RA displayed a spike-and-dome and/or
      plateau morphology. The perfused RA displayed a heterogeneous distribution of
      repolarization, V(max), and spike-and-dome morphology along the epicardial and
      endocardial surfaces as well as transmurally, in the region of the upper crista
      terminalis. I(Kr) block with E-4031 prolonged repolarization homogeneously in the
      perfused RA, whereas I(Kur)/I(to) block using low concentrations of 4
      aminopyridine abbreviated action potential duration at 90% repolarization
      heterogeneously, leading to a reduction in dispersion of repolarization. Our data
      indicate that the electrical heterogeneities, previously described for the canine
      ventricle, also exist within the atria and that I(Kr) block does not accentuate
      and I(Kur)/I(to) block reduces RA dispersion of repolarization. Our study also
      points to major differences in the transmembrane activity recorded using
      superfused vs. arterially perfused atrial preparations.

PMID- 15148062
TI  - Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain
      injury.
AB  - The objective of the present study was to examine the role of the angiotensin II
      type 1 receptor (AT(1)-R) in the diabetes-aggravated oxidative stress and brain
      injury observed in a rat model of combined diabetes and focal cerebral ischemia.
      Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk
      of age. Two weeks after the induction of diabetes, some animals received
      continuous subcutaneous infusion of the AT(1)-R antagonist candesartan (0.5
      mg.kg(-1).day(-1)) for 14 days. Focal cerebral ischemia, induced by middle
      cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ
      injection. Male Sprague-Dawley rats (n = 189) were divided into five groups:
      normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO +
      candesartan. The major observations were that 1) MCAO produced typical cerebral
      infarction and neurological deficits at 24 h that were accompanied by elevation
      of NAD(P)H oxidase gp91(phox) and p22(phox) mRNAs, and lipid hydroperoxide
      production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase
      gp91(phox) and p22(phox) mRNA expression, potentiated lipid peroxidation,
      aggravated neurological deficits, and enlarged cerebral infarction; and 3)
      candesartan reduced the expression of gp91(phox) and p22(phox), decreased lipid
      peroxidation, lessened cerebral infarction, and improved the neurological
      outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H
      oxidase induction, and brain injury induced by focal cerebral ischemia. The
      diabetes-aggravated brain injury involves AT(1)-Rs. We have shown for the first
      time that candesartan reduces brain injury in a combined model of diabetes and
      cerebral ischemia.

PMID- 15148063
TI  - A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and
      hyperlipidemia: a randomized, controlled trial.
AB  - BACKGROUND: Low-carbohydrate diets remain popular despite a paucity of scientific
      evidence on their effectiveness. OBJECTIVE: To compare the effects of a low
      carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol,
      reduced-calorie diet. DESIGN: Randomized, controlled trial. SETTING: Outpatient
      research clinic. PARTICIPANTS: 120 overweight, hyperlipidemic volunteers from the
      community. INTERVENTION: Low-carbohydrate diet (initially, <20 g of carbohydrate
      daily) plus nutritional supplementation, exercise recommendation, and group
      meetings, or low-fat diet (<30% energy from fat, <300 mg of cholesterol daily,
      and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group
      meetings. MEASUREMENTS: Body weight, body composition, fasting serum lipid
      levels, and tolerability. RESULTS: A greater proportion of the low-carbohydrate
      diet group than the low-fat diet group completed the study (76% vs. 57%; P =
      0.02). At 24 weeks, weight loss was greater in the low-carbohydrate diet group
      than in the low-fat diet group (mean change, -12.9% vs. -6.7%; P < 0.001).
      Patients in both groups lost substantially more fat mass (change, -9.4 kg with
      the low-carbohydrate diet vs. -4.8 kg with the low-fat diet) than fat-free mass
      (change, -3.3 kg vs. -2.4 kg, respectively). Compared with recipients of the low
      fat diet, recipients of the low-carbohydrate diet had greater decreases in serum
      triglyceride levels (change, -0.84 mmol/L vs. -0.31 mmol/L [-74.2 mg/dL vs. -27.9
      mg/dL]; P = 0.004) and greater increases in high-density lipoprotein cholesterol
      levels (0.14 mmol/L vs. -0.04 mmol/L [5.5 mg/dL vs. -1.6 mg/dL]; P < 0.001).
      Changes in low-density lipoprotein cholesterol level did not differ statistically
      (0.04 mmol/L [1.6 mg/dL] with the low-carbohydrate diet and -0.19 mmol/L [-7.4
      mg/dL] with the low-fat diet; P = 0.2). Minor adverse effects were more frequent
      in the low-carbohydrate diet group. LIMITATIONS: We could not definitively
      distinguish effects of the low-carbohydrate diet and those of the nutritional
      supplements provided only to that group. In addition, participants were healthy
      and were followed for only 24 weeks. These factors limit the generalizability of
      the study results. CONCLUSIONS: Compared with a low-fat diet, a low-carbohydrate
      diet program had better participant retention and greater weight loss. During
      active weight loss, serum triglyceride levels decreased more and high-density
      lipoprotein cholesterol level increased more with the low-carbohydrate diet than
      with the low-fat diet.

PMID- 15148064
TI  - The effects of low-carbohydrate versus conventional weight loss diets in severely
      obese adults: one-year follow-up of a randomized trial.
AB  - BACKGROUND: A previous paper reported the 6-month comparison of weight loss and
      metabolic changes in obese adults randomly assigned to either a low-carbohydrate
      diet or a conventional weight loss diet. OBJECTIVE: To review the 1-year outcomes
      between these diets. DESIGN: Randomized trial. SETTING: Philadelphia Veterans
      Affairs Medical Center. PARTICIPANTS: 132 obese adults with a body mass index of
      35 kg/m2 or greater; 83% had diabetes or the metabolic syndrome. INTERVENTION:
      Participants received counseling to either restrict carbohydrate intake to <30 g
      per day (low-carbohydrate diet) or to restrict caloric intake by 500 calories per
      day with <30% of calories from fat (conventional diet). MEASUREMENTS: Changes in
      weight, lipid levels, glycemic control, and insulin sensitivity. RESULTS: By 1
      year, mean (+/-SD) weight change for persons on the low-carbohydrate diet was 
      5.1 +/- 8.7 kg compared with -3.1 +/- 8.4 kg for persons on the conventional
      diet. Differences between groups were not significant (-1.9 kg [95% CI, -4.9 to
      1.0 kg]; P = 0.20). For persons on the low-carbohydrate diet, triglyceride levels
      decreased more (P = 0.044) and high-density lipoprotein cholesterol levels
      decreased less (P = 0.025). As seen in the small group of persons with diabetes
      (n = 54) and after adjustment for covariates, hemoglobin A1c levels improved more
      for persons on the low-carbohydrate diet. These more favorable metabolic
      responses to a low-carbohydrate diet remained significant after adjustment for
      weight loss differences. Changes in other lipids or insulin sensitivity did not
      differ between groups. LIMITATIONS: These findings are limited by a high dropout
      rate (34%) and by suboptimal dietary adherence of the enrolled persons.
      CONCLUSION: Participants on a low-carbohydrate diet had more favorable overall
      outcomes at 1 year than did those on a conventional diet. Weight loss was similar
      between groups, but effects on atherogenic dyslipidemia and glycemic control were
      still more favorable with a low-carbohydrate diet after adjustment for
      differences in weight loss.

PMID- 15148066
TI  - Clarifying adverse drug events: a clinician's guide to terminology,
      documentation, and reporting.
AB  - Adverse drug events cause substantial morbidity and mortality, yet they remain
      underappreciated and misunderstood. The terminology to describe errors and
      patient harm associated with medications causes much confusion. This article uses
      the case study of a patient with multiple adverse drug events to clarify key
      terms, such as adverse event, adverse drug reaction, adverse drug event,
      medication error, and side effect. The case discussion illustrates clinical
      approaches to analyzing the causal connection between a suspect drug and an
      adverse event. Examples and rationale for meaningful documentation of adverse
      drug events are provided, along with an outline of the types of events that
      should be reported to regulatory agencies.

PMID- 15148065
TI  - Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled
      trial.
AB  - BACKGROUND: Patients with HIV infection who are treated with antiretroviral
      agents often lose subcutaneous fat and have metabolic abnormalities, including
      insulin resistance and reduced adiponectin levels, which may be related to
      disrupted subcutaneous adipogenesis and altered peroxisome proliferator-activated
      receptor-gamma signaling. OBJECTIVE: To investigate the effects of rosiglitazone
      (4 mg/d), a peroxisome proliferator-activated receptor-gamma agonist, in HIV
      infected men and women with hyperinsulinemia and lipoatrophy. DESIGN: A
      randomized, double-blind, placebo-controlled, 3-month study. SETTING: University
      hospital. PATIENTS: 28 HIV-infected men and women with hyperinsulinemia and
      lipoatrophy. MEASUREMENTS: Insulin sensitivity measured by euglycemic
      hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed
      tomography; adiponectin, free fatty acid, and lipid levels; and safety variables.
      RESULTS: Rosiglitazone, when compared with placebo, improved insulin sensitivity
      (mean [+/-SD] change, 1.5 +/- 2.1 mg of glucose/kg of lean body mass per minute
      vs. -0.4 +/- 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean
      [+/-SD], 2.2 +/- 2.2 micro g/mL vs. 0.1 +/- 1.1 microg/mL; P = 0.006), and
      reduced free fatty acid levels (mean [+/-SD], -0.09 +/- 0.1 mmol/L vs. 0.01 +/-
      0.1 mmol/L; P = 0.02). Mean percentage (+/-SD) of body fat (1.38% +/- 3.03% vs. 
      0.83% +/- 2.76%; P = 0.03) and subcutaneous leg fat area (2.3 +/- 8.4 cm2 vs. 
      0.9 +/- 1.9 cm2; P = 0.02) increased significantly with rosiglitazone compared
      with placebo. Mean total cholesterol levels (+/-SD) also increased with
      rosiglitazone compared with placebo (0.6 +/- 1.0 mmol/L [25 +/- 37 mg/dL] vs. 
      0.4 +/- 0.6 mmol/L [-15 +/- 25 mg/dL]; P = 0.007). LIMITATIONS: The study was
      relatively small and of short duration. CONCLUSIONS: The authors demonstrated
      positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and
      metabolic indices, including adiponectin levels, in HIV-infected patients with
      lipoatrophy and insulin resistance. Peroxisome proliferator-activated receptor
      gamma agonists may correct the metabolic abnormalities associated with disrupted
      adipogenesis in this population. Further studies must determine the clinical
      utility of such agents in HIV-infected patients.

PMID- 15148067
TI  - Meta-analysis: respiratory tolerance to regular beta2-agonist use in patients
      with asthma.
AB  - BACKGROUND: The regular administration of beta2-agonists may be associated with
      the development of tolerance to their effects. PURPOSE: To assess the effect of
      regular beta2-agonist use on respiratory function and beta2-receptor function in
      asthmatic patients. DATA SOURCES: Comprehensive searches of the EMBASE, MEDLINE,
      and CINAHL databases from 1966 to June 2003 and references of identified articles
      and reviews. STUDY SELECTION: Randomized, placebo-controlled trials that studied
      at least 1 week of regular beta2-agonist administration in patients with asthma
      and did not allow "as-needed" beta2-agonist use in the placebo group. DATA
      EXTRACTION: Outcomes measured in the active treatment and placebo groups were the
      change in FEV1 in response to treatment and subsequent beta2-agonist
      administration, the provocative concentration of bronchoconstrictive agents
      causing a 20% reduction in FEV1 (PC20), and in vitro variables of leukocyte beta2
      receptor function. DATA SYNTHESIS: Pooled results of 22 trials showed that
      regular beta2-agonist use, compared with placebo, did not change the mean FEV1
      after treatment or the net FEV1 treatment effect but substantially reduced the
      following: the peak FEV1 response to subsequent beta2-agonist administration
      (change, -17.8% [95% CI, -27.2% to -8.5%]); the FEV1 dose response to subsequent
      beta2-agonists (-34.8% [CI, -45.7% to -24%]); the PC20 to combined
      bronchoconstrictive stimuli (-26% [CI, -37% to -11%]); and leukocyte beta2
      receptor density (-18.3% [CI, -31.6% to -5.1%]), binding affinity (-23.1% [CI, 
      39.4% to -6.8%]), and in vitro response to isoproterenol (-32.7% [CI, -56.5% to 
      9.0%]). CONCLUSION: Regular beta2-agonist use for at least 1 week in patients
      with asthma results in tolerance to the drug's bronchodilator and
      nonbronchodilator effects and may be associated with poorer disease control
      compared with placebo.

PMID- 15148068
TI  - Reducing resident work hours: unproven assumptions and unforeseen outcomes.

PMID- 15148069
TI  - Benefits of resident work hours regulation.

PMID- 15148070
TI  - The effect of work hour regulations on personal development during residency.

PMID- 15148071
TI  - Screening for suicide risk: recommendation and rationale.
AB  - This statement summarizes the current U.S. Preventive Services Task Force
      (USPSTF) recommendations on screening for suicide risk and the supporting
      scientific evidence and updates the 1996 recommendations on this topic. The
      complete information on which this statement is based, including evidence tables
      and references, is available in the accompanying article in this issue and in the
      systematic evidence review on this topic, which is available through the USPSTF
      Web site (www.preventiveservices.ahrq.gov) and through the National Guideline
      Clearinghouse (www.guideline.gov). The complete recommendation statement and the
      summary of the evidence are also available from the Agency for Healthcare
      Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail,
      ahrqpubs@ahrq.gov).

PMID- 15148072
TI  - Screening for suicide risk in adults: a summary of the evidence for the U.S.
      Preventive Services Task Force.
AB  - BACKGROUND: Suicide is the 11th leading cause of death and the seventh leading
      cause of years of potential life lost in the United States. Although suicide is
      of great public health significance, its clinical management is complicated.
      PURPOSE: The authors systematically reviewed the literature to determine whether
      screening for suicide risk in primary care settings decreases morbidity,
      mortality, or both. DATA SOURCES: MEDLINE (1966 to 17 October 2002), PsycINFO,
      Cochrane databases, hand-searched bibliographies, and experts. STUDY SELECTION:
      For screening, only English-language studies performed in primary care settings
      were examined. For treatment, randomized, controlled trials and cohort studies
      were included if they were performed in any setting where suicide completions,
      suicide attempts, or suicidal ideation were reported. DATA EXTRACTION: A primary
      reviewer abstracted data on key variables of study sample, design, and outcomes;
      a second reviewer checked information accuracy against the original articles.
      DATA SYNTHESIS: No study directly addressed whether screening for suicide in
      primary care reduces morbidity and mortality. The remainder of the review focused
      on the questions of reliable screening tests for suicide risk and the
      effectiveness of interventions to decrease depression, suicidal ideation, and
      suicide attempts or completion. One screening study provided limited evidence for
      the accuracy of suicide screening in a primary care setting. Intervention studies
      provided fair and mixed evidence that treating those at risk for suicide reduces
      the number of suicide attempts or completions. The evidence suggests mild to
      moderate improvement for interventions addressing intermediate outcomes such as
      suicidal ideation, decreased depressive severity, decreased hopelessness, or
      improved level of function. CONCLUSION: Because of the complexity of studying the
      risk for suicide and the paucity of well-designed research studies, only limited
      evidence guides the primary care clinician's assessment and management of suicide
      risk.

PMID- 15148073
TI  - Reduced-carbohydrate diets: no roll in weight management?

PMID- 15148074
TI  - How many hours is enough? An old profession meets a new generation.

PMID- 15148075
TI  - Obstetricians wanted: no mothers need apply.

PMID- 15148076
TI  - Dr. Mommy blues.

PMID- 15148077
TI  - Cost-effectiveness of mammography for older women.

PMID- 15148078
TI  - Saving office practice.

PMID- 15148079
TI  - Saving office practice.

PMID- 15148080
TI  - Management options for patients with ulcer hemorrhage.

PMID- 15148081
TI  - Saving office practice.

PMID- 15148083
TI  - Actual versus perceived workload for house officers: black cloud looming?

PMID- 15148082
TI  - High-dose vitamin C and iron overload.

PMID- 15148084
TI  - Virulence factors predict Escherichia coli colonization patterns among human and
      animal household members.

PMID- 15148085
TI  - Epinephrine-secreting pheochromocytoma presenting with cardiogenic shock and
      profound hypocalcemia.

PMID- 15148086
TI  - Finland pioneers international suicide prevention.

PMID- 15148087
TI  - Summaries for patients. Effectiveness and safety of low-carbohydrate diets.

PMID- 15148088
TI  - Summaries for patients. Weight loss and results of low-carbohydrate diets.

PMID- 15148089
TI  - Summaries for patients. Rosiglitazone treatment for fat redistribution and
      metabolic abnormalities caused by anti-HIV therapy.

PMID- 15148090
TI  - Summaries for patients. Tolerance to beta2-agonist treatment after regular use in
      people with asthma.

PMID- 15148091
TI  - Summaries for patients. Screening to identify primary care patients who are at
      risk for suicide: recommendations from the U.S. Preventive Services Task Force.

PMID- 15148092
TI  - How do physicians think about successful aging?

PMID- 15148093
TI  - 308-nm excimer laser for the treatment of scalp psoriasis.

PMID- 15148094
TI  - Skin signs as the presenting manifestation of severe nutritional deficiency:
      report of 2 cases.

PMID- 15148095
TI  - Comparison of skin biopsy triage decisions in 49 patients with pigmented lesions
      and skin neoplasms: store-and-forward teledermatology vs face-to-face
      dermatology.
AB  - OBJECTIVE: To determine the relative efficacy of store-and-forward
      teledermatology vs face-to-face dermatology consultations in triage decisions
      about the need for a biopsy of neoplastic skin changes. DESIGN: Prospective study
      of consecutive patients judged by an internist to require dermatologic
      consultation for a skin growth. SETTING: Private primary care and dermatology
      practices and an academic dermatology practice. PATIENTS: Patients requiring
      dermatology consultation for evaluation of skin growths. Patients were seen by a
      single primary care physician between July 10, 1998, and August 4, 2000.
      INTERVENTION: Digital photographs of skin growths were obtained by the primary
      care physician and evaluated by a teledermatologist. The patient was then seen
      face-to-face by a dermatologist. A biopsy was performed if either dermatologist
      favored biopsy. MAIN OUTCOME MEASURES: Decisions to perform a biopsy. Agreement
      between the dermatologists was assessed. RESULTS: Of the 49 patients with
      evaluable photographs, the face-to-face dermatologist and teledermatologist
      recommended a biopsy for the same 26 patients, yielding a sensitivity of the
      teledermatologist of 1.00 (95% confidence interval [CI], 0.87-1.00) and a
      specificity of 1.00 (95% CI, 0.85-1.00). The agreement between the dermatologists
      (kappa) was 1.00 (95% CI, 0.72-1.00). CONCLUSION: Store-and-forward
      teledermatology may provide an accurate and cost-effective method of determining
      whether skin growths in patients presenting to primary care physicians should
      undergo biopsy.

PMID- 15148096
TI  - Full-body skin examinations: the patient's perspective.
AB  - OBJECTIVES: To determine (1). primary care practitioner (PCP) and dermatologist
      full-body skin examination (FBSE) rates by using a patient questionnaire and (2).
      whether patient risk factors for skin cancer alter these rates. DESIGN:
      Questionnaires pertaining to whether participants underwent regular FBSE, their
      feelings about this screening test, and their risks for developing skin cancer.
      SETTING: The primary care and dermatology clinics at the West Haven Veterans
      Affairs Medical Center. PARTICIPANTS: A convenience sample of 356 patients
      awaiting clinic appointments. Of those asked to participate, 251 (71%) agreed.
      MAIN OUTCOME MEASURES: Patient report of undergoing FBSE, attitudes regarding
      this examination, and risk factors for cutaneous malignancy. RESULTS: Thirty-two
      percent of all respondents reported undergoing regular FBSE by their PCP, whereas
      55% of those with a history of skin cancer reported undergoing FBSE. Eight
      percent of participants reported embarrassment with FBSE, 83% reported that their
      PCP would be considered thorough by performing FBSE, and 87% would like their PCP
      to perform FBSE regularly. Only 2% of participants would refuse the examination
      if the PCP were of the opposite sex, whereas 8% would be more willing to be
      examined. CONCLUSIONS: Although patients report a low incidence of FBSE, those
      with a personal history of skin cancer are more likely to be screened. A low rate
      of embarrassment and a high rate of perceived PCP thoroughness are associated
      with FBSE. Patients have a strong preference to undergo FBSE. A sex difference
      between the PCP and the patient should not be a barrier to this examination.

PMID- 15148097
TI  - Dermoscopic patterns of benign volar melanocytic lesions in patients with
      atypical mole syndrome.
AB  - BACKGROUND: Acral benign melanocytic lesions in white populations, particularly
      in subjects with atypical mole syndrome, have been poorly characterized until
      recently. The advent of dermoscopy has enabled more specific diagnoses of these
      pigmented skin lesions. OBJECTIVE: To evaluate the clinical and dermoscopic
      features of benign volar lesions in a group of white patients with atypical mole
      syndrome. SETTING: A private medical center specializing in early diagnosis of
      malignant melanoma and a melanoma unit in a university hospital. METHODS: Acral
      melanocytic lesions in 511 patients with atypical mole syndrome were studied
      using standard clinical assessment and dermoscopy. RESULTS: Two hundred ten acral
      melanocytic lesions were observed in 156 of the patients: 165 lesions were
      present on the soles of 121 patients and 45 lesions on the palms of 35 patients.
      No acral malignant lesions were detected. We observed the following patterns of
      lesions: parallel furrow in 111 lesions (52.9%), latticelike in 26 lesions
      (12.4%), fibrillar or filamentous in 13 lesions (6.2%), and nontypical in 29
      lesions (13.8%). In 31 lesions (14.8%), we observed 3 previously undefined
      patterns: a globular pattern in 11 lesions (5.2%), a homogeneous pattern in 15
      lesions (7.1%), and an acral reticular pattern in 5 lesions (2.4%). CONCLUSIONS:
      We observed a greater number of benign melanocytic lesions in glabrous skin than
      expected, probably related to our cohort selection of patients with atypical mole
      syndrome, although the lesions generally exhibited patterns on dermoscopy similar
      to those seen in Japanese studies. We defined 3 new benign dermoscopic patterns,
      which will enable better characterization of acral lesions.

PMID- 15148098
TI  - The Framingham school nevus study: a pilot study.
AB  - OBJECTIVES: To (1). describe nevus patterns using digital photography and
      dermoscopy; (2). evaluate the relationship between host and environmental factors
      and prevalence of nevi in schoolchildren; and (3). demonstrate the feasibility of
      conducting a longitudinal study. DESIGN: Cross-sectional survey and 1-year
      prospective follow-up study. PARTICIPANTS: Students from 2 classrooms, grades 6
      and 7, in the Framingham, Mass, school system (N = 52). MAIN OUTCOME MEASURES: A
      survey was completed by students and 1 of their parents that included questions
      on demographic and phenotypic characteristics, family history of skin cancer, and
      sun exposure and protection practices. An examination of nevi on the back was
      performed that included digital photography and digital dermoscopy. Follow-up
      child and parent surveys and examinations were conducted at 1-year follow-up.
      RESULTS: At baseline, the median number of back nevi was 15 (mean [SD], 21.9
      [15.3]). Older age, male sex, fair skin, belief that a tan is healthier, tendency
      to burn, and sporadic use of sunscreen were positively associated with mole
      count, although age was the only statistically significant factor. Predominant
      dermoscopic patterns for the index nevus were as follows: 38% globular, 14%
      reticulated, 38% structureless, and 10% combinations of the above patterns with
      no predominant characteristic. The overall participation rate from baseline to
      follow-up was 81% (42/52) for the skin examination process. At the 1-year follow
      up examination, new nevi were identified in 36% of students (n = 15), while 9.6%
      of baseline index nevi had changes in the dermoscopic pattern. Dominant
      dermoscopic pattern was related to nevus size: smaller nevi tended to be
      structureless, while larger nevi were of mixed pattern. CONCLUSION: This study
      supports the feasibility and utility of digital photography and dermoscopy for
      the longitudinal study of nevus evolution in early adolescence.

PMID- 15148099
TI  - Management of lentigo maligna and lentigo maligna melanoma with staged excision:
      a 5-year follow-up.
AB  - OBJECTIVE: To assess the long-term cure rate for treatment of lentigo maligna
      (LM) and lentigo maligna melanoma (LMM) by means of a staged, margin-controlled,
      vertical-edged excision with rush permanent specimens and a radial sectioning
      technique. DESIGN: Retrospective follow-up study. SETTING: University-affiliated
      and private-practice dermatologic surgery clinics. PATIENTS: Fifty-nine patients
      treated for 55 LMs and 7 LMMs between January 1, 1990, and December 31, 2001.
      INTERVENTIONS: The technique included vertical excision with initial 2- to 3-mm
      margins examined by rush permanent sections (prepared and read within 24 hours).
      Further excision took place as guided by histologic findings. Data on patient and
      lesion characteristics were obtained via a medical chart review. Patients were
      then contacted and examined for local recurrence. Biopsies were performed on all
      patients with possible recurrence on clinical examination. MAIN OUTCOME MEASURES:
      Local recurrence of LM or LMM. RESULTS: After a mean follow-up of 57 months
      (median, 54 months; 293.8 person-years), 95% of patients were free of recurrence.
      Three patients had local recurrence and no patients had evidence of metastasis.
      Two of the 3 local recurrences were of previously excised LM, and 1 was of an
      LMM. Half (32) of all lesions required 2 or more stages. One required more than 4
      stages. The average margin of excision was 0.55 cm. Three of the 58 lesions read
      as LM on biopsy were found to have invasive disease (LMM) at the time of
      definitive excision. CONCLUSIONS: The technique described herein for the
      treatment of LM and LMM provides a long-term disease-free survival of 95%. The
      cure rate is greater than that reported for standard excision and is similar to
      that for other margin-control techniques. To our knowledge, this is the largest
      reported study and has the longest follow-up for this excision method for LM and
      LMM.

PMID- 15148100
TI  - Acaricidal activity of Melaleuca alternifolia (tea tree) oil: in vitro
      sensitivity of sarcoptes scabiei var hominis to terpinen-4-ol.
AB  - OBJECTIVE: To compare the acaricidal activity of Melaleuca alternifolia (tea
      tree) oil (TTO) and some of its individual active components on the itch mite
      Sarcoptes scabiei var hominis. DESIGN: In vitro acaricide sensitivity assessment.
      SETTING: The Menzies School of Health Research laboratory, located near the
      Infectious Diseases Ward of the Royal Darwin Hospital, Australia, where patients
      are admitted and treated for crusted scabies. PARTICIPANTS: Scabies mites (S
      scabiei var hominis) were collected from a 20-year-old Aboriginal woman admitted
      to the Royal Darwin Hospital with crusted scabies. Interventions Within 3 hours
      of collection, scabies mites were placed in continuous direct contact with the
      TTO products and control acaricides and were observed at regular intervals. MAIN
      OUTCOME MEASURES: Percentage of mites dead at regular observation intervals
      between 5 minutes and 24 hours during continuous exposure to the TTO products and
      acaricides. RESULTS: The 5% TTO and active component terpinen-4-ol were highly
      effective in reducing mite survival times. Statistically significant differences
      in mite survival curves were observed for 5% TTO, 2.1% terpinen-4-ol, 5%
      permethrin, and ivermectin (100 microg/g of Emulsifying Ointment British
      Pharmacopoeia 88). In vivo effectiveness was also observed. CONCLUSIONS:
      Documentation of resistance against antiectoparasitic compounds is increasing.
      Reported S scabiei treatment failures with lindane, crotamiton, and benzyl
      benzoate, as well as likely emerging resistance to 5% permethrin and oral
      ivermectin, are of concern and advocate for the identification and development of
      novel acaricidal drugs. Tea tree oil is a membrane-active biocide extracted from
      the tree M alternifolia. It is a principal antimicrobial in a wide range of
      pharmaceuticals sold in Australia, with the main active component being
      oxygenated terpenoids. The results suggest that TTO has a potential role as a new
      topical acaricide and confirm terpinen-4-ol as the primary active component.

PMID- 15148101
TI  - Elevated serum granulocyte colony-stimulating factor levels in patients with
      active phase of sweet syndrome and patients with active behcet disease:
      implication in neutrophil apoptosis dysfunction.
AB  - BACKGROUND: Sweet syndrome (SS), an acute inflammatory disease, has clinical and
      laboratory features similar to those of Behcet disease (BD). Serum levels of
      granulocyte colony-stimulating factor (G-CSF) are elevated in patients with SS,
      and exogenous administration of G-CSF has repeatedly been implicated in the
      causation of SS. Granulocyte colony-stimulating factor is a hematopoietic growth
      factor that regulates the production and differentiation of neutrophils.
      OBJECTIVES: To clarify the role of elevated serum G-CSF levels in patients with
      active SS and active BD compared with those with inactive SS or BD and healthy
      controls. To then analyze neutrophil apoptosis in the active state of SS and BD;
      and to also investigate the influence of autologous serum on neutrophil
      apoptosis. METHODS: Serum G-CSF was examined in 5 patients with active SS, 7 with
      inactive SS, 7 with active BD, 9 with inactive BD, and 5 healthy controls by
      means of an enzyme immunoassay kit. We measured apoptotic cells in the neutrophil
      fraction of peripheral blood collections in patients with active diseases and
      controls by means of flow cytometry. RESULTS: Serum G-CSF level was significantly
      higher in patients with active SS than in those with inactive SS. The difference
      in serum G-CSF levels among patients with active and inactive BD was also
      significant. Serum G-CSF level was significantly higher in patients with active
      SS than in those with active BD. Neutrophil apoptosis was significantly higher in
      patients with active SS than healthy controls. This increased apoptosis rate was
      also seen in patients with active BD. The increased rate of neutrophil apoptosis
      was significantly suppressed when the neutrophils were cultured for 18 hours in
      the presence of autologous active SS serum. Similarly, neutrophil apoptosis was
      suppressed in the presence of autologous serum in patients with active BD, but
      not significantly so. CONCLUSIONS: These findings indicate that increased
      production of G-CSF in patients with SS and BD may play an important role in the
      manifestation of these disorders. Given the suppression of neutrophil apoptosis
      in the active state in the presence of the influence of autologous serum, which
      includes elevated G-CSF level, we propose that serum G-CSF plays a significant
      role in the suppression of neutrophil apoptosis. Furthermore, G-CSF-induced
      suppression of neutrophil apoptosis appears to be deeply involved in the
      pathogenesis of SS and BD.

PMID- 15148102
TI  - Is high mole count a marker of more than melanoma risk? Eczema diagnosis is
      associated with melanocytic nevi in children.
AB  - BACKGROUND: The number of melanocytic nevi is the best single marker of increased
      melanoma risk. In a previous study, adults with severe eczema were reported to
      have significantly fewer nevi than adults without eczema. OBSERVATIONS: In a
      nested case-control design within a randomized, controlled interventional trial
      of additional sun protection vs standard care in 269 children, a history of
      eczema was reported by the parents of 44 (16%) of the children. More nevi were
      found in children with a parental report of previous eczema diagnosis than in
      children without reported eczema (median, 7.5 nevi vs 5.0 nevi; P =.01). Eczema
      diagnosis was most significantly associated with more melanocytic nevi in
      children with lightly pigmented skin (8.5 nevi vs 6.0 nevi; P <.001). In
      multivariate logistical regression analysis, including assessment of hair color,
      sun protection practices, and study assignment (intervention vs standard care),
      eczema status remained significantly predictive of nevi number in children (P
      <.001). CONCLUSIONS: In contrast to a previous study that associated severe
      eczema with fewer nevi in adults, in the present study children with a reported
      history of eczema had more nevi than children without a reported history of
      eczema.

PMID- 15148105
TI  - Association of solitary, segmental hemangiomas of the skin with visceral
      hemangiomatosis.
AB  - BACKGROUND: Multiple hemangiomas of the skin have traditionally been recognized
      as a clue to potential visceral hemangiomas. Recently, hemangiomas have been
      recognized to have subcategories, localized and segmental, which correlate with
      risk of complications. While less common, segmental hemangiomas of the skin have
      a higher risk of being life- or function-threatening and/or having associated
      structural anomalies such as those that occur in PHACE (posterior fossa brain
      malformations, hemangiomas, arterial anomalies, coarctation of the aorta and
      cardiac defects, and eye abnormalities) syndrome (PHACES, if sternal
      clefting/supraumbilical raphe is included). However, the potential association of
      solitary, segmental hemangiomas of the skin with visceral hemangiomatosis has not
      been previously emphasized. OBSERVATIONS: A total of 47 cases of segmental
      hemangiomas of the skin in association with visceral hemangiomatosis were found.
      The location of the cutaneous hemangiomas most commonly, but not exclusively,
      involved the face (37 cases [79%]). The most common site of internal organ
      involvement was the liver (20 cases [43%]), followed by the gastrointestinal
      tract (16 [34%]), brain (16 [34%]), mediastinum (9 [19%]), and lung (7 [15%]).
      The percentages of reported cases of hemangiomas of the pancreas, spleen, bones,
      or kidneys were 6% or less. Forty percent of patients met criteria for the
      diagnosis of PHACE(S) syndrome. In this subgroup, internal organ hemangiomas were
      most commonly found in the brain or mediastinum (18 cases [53%]). Overall, 12
      patients (25%) died during infancy, most commonly because of gastrointestinal
      involvement or congestive heart failure secondary to liver involvement.
      Conclusion Segmental hemangiomas of the skin have an associated risk of visceral
      hemangiomatosis, with the potential of causing vital organ compromise.

PMID- 15148106
TI  - Multifocal lymphangioendotheliomatosis with thrombocytopenia: a newly recognized
      clinicopathological entity.
AB  - BACKGROUND: Severe thrombocytopenic coagulopathy may complicate platelet-trapping
      vascular tumors such as kaposiform hemangioendothelioma and tufted angioma. Low
      grade, chronic consumptive coagulopathy may occur with extensive venous and
      lymphatic malformations. We have also observed patients with rare multifocal,
      congenital skin and gastrointestinal (GI) tract vascular anomalies of distinctive
      and remarkably similar appearance, all associated with coagulopathy. We studied
      the clinical and histopathologic features of 3 patients demonstrating this
      previously uninvestigated phenomenon. OBSERVATIONS: All 3 patients presented with
      hundreds of congenital red-brown skin plaques as large as a few centimeters, with
      similar lesions throughout the GI tract and severe GI tract bleeding. One patient
      had synovial involvement. All had significant thrombocytopenia, with prothrombin
      and partial thromboplastin times and fibrinogen levels near the reference range.
      Corticosteroids and/or interferon alfa treatment resulted in equivocal or no
      improvement. Skin lesions from all 3 patients were histologically distinctive and
      similar, including dilated, thin-walled vessels in the dermis and subcutis lined
      by hobnailed, proliferative endothelial cells (10%-15% immunoreactive for Ki-67),
      most displaying intraluminal papillary projections. Immunoreaction for the
      lymphatic marker LYVE-1 was uniformly present. CONCLUSIONS: We propose the term
      multifocal lymphangioendotheliomatosis with thrombocytopenia to distinguish this
      newly recognized clinicopathological entity. These congenital lesions, like
      tufted angioma and kaposiform hemangioendothelioma, show lymphatic
      differentiation, strengthening the association between abnormal lymphatic
      endothelium and coagulopathy.

PMID- 15148104
TI  - Unexplained hypereosinophilia and the need for cytogenetic and molecular genetic
      analyses.
AB  - BACKGROUND: Idiopathic hypereosinophilic syndrome (HES) is a diagnosis made after
      the exclusion of other causes of eosinophilia. However, differentiation of
      idiopathic HES from eosinophilic leukemia is sometimes difficult. In some cases,
      these diagnoses can be differentiated by cytogenetic or molecular findings, as
      illustrated in the patients described herein. OBSERVATIONS: We describe 3
      patients with HES and associated pruritus; 1 patient also had recurrent lesions
      of eosinophilic cellulitis. All 3 patients were initially diagnosed as having
      idiopathic HES, but after evaluation and demonstration of molecular
      abnormalities, they were classified as having eosinophilic leukemia. CONCLUSIONS:
      Patients with a diagnosis of idiopathic HES should be evaluated for cytogenetic
      or molecular genetic abnormalities. These abnormalities can establish a diagnosis
      of chronic eosinophilic leukemia and may provide clues for emerging therapies.

PMID- 15148107
TI  - Surgical margins for lentigo maligna, 2004.

PMID- 15148108
TI  - A large friable tumor overlying the left side of the mandible--case.

PMID- 15148109
TI  - Adjacent dermal nodules on the nose--case.

PMID- 15148110
TI  - Nodule on the back of a 73-year-old woman--case.

PMID- 15148111
TI  - Multiple hyperkeratotic plaques and lower extremity weakness--case.

PMID- 15148112
TI  - Dermoscopy vs capillaroscopy of nontumoral dermatoses.

PMID- 15148114
TI  - Teloptosis and kenogen: two new concepts in human trichology.

PMID- 15148113
TI  - Eruptive xanthomas associated with protease inhibitor therapy.

PMID- 15148115
TI  - How accurate is a clinical diagnosis of erythema chronicum migrans? Prospective
      study comparing the diagnostic accuracy of general practitioners and
      dermatologists in an area where lyme borreliosis is endemic.

PMID- 15148116
TI  - Alleviation of erythromelalgia with venlafaxine.

PMID- 15148117
TI  - Getting sunburned, or how to harm my younger siblings?

PMID- 15148118
TI  - Severe generalized deep dermatophytosis due to Trichophyton rubrum (trichophytic
      granuloma) in a patient with atopic dermatitis.

PMID- 15148119
TI  - Dermoscopy of melanocytic neoplasms: familial patterns.

PMID- 15148120
TI  - Long-term results of lower-lid suspension blepharoplasty: a 30-year experience.
AB  - BACKGROUND: Muscle suspension blepharoplasty remains a reliable method to tighten
      the loose skin and muscle of the lower eyelid. OBJECTIVE: To evaluate the 30-year
      experience of the senior author (N.J.P.) with the skin-muscle suspension
      technique for lower-lid blepharoplasty. PATIENTS AND METHODS: Of 4395 patients
      who underwent lower-lid blepharoplasty, 3988 had muscle suspension blepahroplasty
      performed with adequate follow-up. RESULTS: Results of the 30-year review showed
      that most patients were very satisfied with the procedure. There were 67
      complications (2 hematomas, 1 poor scar, 24 cases of scleral show <1 mm, and 40
      cases of chemosis). Chemosis resolved in 2 to 8 weeks, and there were no cases of
      ectropion, scleral show greater than 1 mm, dry eye, or vision loss. Revision
      surgery was needed in 41 patients, all of whom were satisfied after the secondary
      procedure. CONCLUSION: Despite the recent drift toward orbital fat preservation
      for lower-lid blepharoplasty, conventional lower-lid muscle suspension offers the
      surgeon a reliable method to tighten the loose skin and muscle of the lower
      eyelid and give the patient a more attractive, youthful appearance.

PMID- 15148121
TI  - Persistent blurred vision after blepharoplasty and ptosis repair.
AB  - BACKGROUND: Visual disturbance after upper (eyelid) blepharoplasty is a
      relatively common postoperative complaint. Recent ophthalmology literature has
      demonstrated alternations of corneal curvature after procedures that reposition
      the upper eyelid using corneal topography. Astigmatic changes induced by eyelid
      repositioning may be a cause of persistent blurred vision after upper eyelid
      procedures. This observation has not been reported in the facial plastic
      literature. OBJECTIVE: To determine the incidence of persistent visual
      disturbance after upper blepharoplasty. METHODS: A retrospective review of upper
      blepharoplasty by 1 facial plastic surgeon and 2 oculoplastic surgeons during the
      year 2000. Patient interviews were conducted via telephone. RESULTS: A total of
      146 patients were identified, and 106 of them responded to the study request. Six
      patients (5.7%) had subjective visual acuity changes 1 year after upper
      blepharoplasty, and 4 of the 6 patients had combined blepharoplasty and ptosis
      repair. Three patients had worse vision, 2 had improved vision, and 1 was unable
      to wear rigid contact lenses because of fogging. CONCLUSIONS: Prior studies have
      shown that most patients have measurable astigmatic changes 3 months after
      blepharoplasty and ptosis repair. We found that only a small percentage of them
      have persistent subjective symptoms 1 year postoperatively. It is important for
      facial plastic surgeons to properly advise patients, especially those with
      combined procedures, that upper eyelid repositioning procedures may induce long
      term vision changes. Patients may need to obtain new prescription spectacles and
      contact lenses postoperatively.

PMID- 15148122
TI  - Occurrence of subclinical tumor in excised facial subunits.
AB  - OBJECTIVE: To determine the incidence of subclinical tumor in excised facial
      subunits in patients undergoing reconstruction after Mohs surgery. DESIGN: The
      study group comprised 45 patients who had their Mohs defects repaired by a facial
      plastic surgeon at a tertiary care center (university hospital). In the group,
      there were 74 biopsy-proved cutaneous neoplasms of the face. The median age of
      the group was 67 years. Nineteen patients (42%) had multiple tumors. There were
      63 basal cell carcinomas (85%) and 11 squamous cell carcinomas (15%). Forty-seven
      tumors (64%) were primary and 27 (36%) were recurrent. Reconstruction of the
      defects was based on the principle of aesthetic subunits. Excised subunits were
      examined by the Mohs surgeon. Further excisions were performed, as necessary, if
      tumor was present in the subunit. RESULTS: Five patients (11%) had subclinical
      basal cell carcinomas in their excised facial subunits. Four patients underwent
      further resections. CONCLUSIONS: In patients with severe sun damage, recurrent
      tumors, and a history of skin cancer, clinically normal tissue excised during the
      reconstruction of their Mohs defects may contain subclinical tumor. Consequently,
      when these "high-risk" patients undergo reconstruction, excised facial subunits
      should be submitted for pathologic examination.

PMID- 15148123
TI  - Self-induced nasal ulceration.
AB  - BACKGROUND: Nasal ulcerations have many causes. Ulcerations that are self-induced
      are difficult to diagnose and treat. Two rare conditions with self-induced nasal
      ulceration are trigeminal trophic syndrome (TTS) and factitious disorder (FD).
      Trigeminal trophic syndrome is characterized by trigeminal anesthesia, nasal alar
      ulceration, and facial paresthesia. Appearance of the nasal ulcer after
      trigeminal ablation for neuralgia is diagnostic. Self-induced nasal lesions that
      occur in FD are primarily distinguished from those in TTS by the presence of
      normal trigeminal nerve function and frequent patient denial of lesion
      manipulation. OBJECTIVES: To increase physician awareness of the disorders
      leading to self-induced nasal ulceration and to discuss management issues in our
      patient series. DESIGN: A retrospective review of 7 cases in which the patients
      presented for reconstructive consultation between March 1985 and October 1997 and
      were found to have self-induced nasal ulcerations. SETTING: Tertiary university
      medical center. RESULTS: Five patients were identified with TTS and underwent
      nasal reconstruction an average of 43 months (range, 4-72 months) after nasal
      ulcer presentation. Four of the 5 patients developed ulcer recurrence between 1
      and 58 months after reconstruction; secondary reconstruction resulted in
      recurrence in 2 of these patients. Two patients were identified with FD and self
      induced nasal ulceration. One of these 2 patients underwent total nasal
      reconstruction 15 months after ulcer occurrence and developed recurrence 2 weeks
      after surgery. CONCLUSIONS: Self-induced nasal ulceration remains a difficult
      condition to diagnose and treat. Readily treatable conditions should be excluded,
      and diagnostic workup should include tissue biopsy and laboratory studies.
      Patients with TTS may have associated ocular findings, and those who do should be
      referred for ophthalmologic consultation. Surgical reconstruction can be
      considered in the highly motivated patient with TTS; however, delayed ulcer
      recurrence is common. Patients with FD should be treated primarily with local
      wound care and referred for psychiatric intervention. We strongly recommend nasal
      prosthetic devices as the primary means of aesthetic correction and discourage
      surgical repair in the patient with FD.

PMID- 15148124
TI  - Nasal valve reconstruction: experience in 53 consecutive patients.
AB  - OBJECTIVES: To determine the cause of nasal valve obstruction in a series of
      patients requiring surgical correction, to evaluate the efficacy of our surgical
      techniques, and to assess the cosmetic effect of nasal valve repair. METHODS:
      Retrospective review of 53 consecutive cases involving adult patients who
      underwent nasal valve reconstruction over an 8-year period. The preoperative
      symptom severity, cause of nasal valve obstruction, preoperative photographs,
      anatomical findings at the time of surgery, and reconstructive techniques were
      reviewed. Postoperative photographs and resolution of symptoms were analyzed.
      RESULTS: The most common cause of nasal valve obstruction was previous
      rhinoplasty (79%), followed by nasal trauma (15%) and congenital anomaly (6%).
      Spreader grafts were used in 42 patients (79%), and alar batten grafts were used
      in 19 patients (36%). The patients received a minimum of 1 year of follow-up. All
      12 patients with external valve dysfunction showed improvement after surgery.
      Thirteen (93%) of the 14 patients with concomitant external and internal valve
      dysfunction had improvement in nasal obstruction after treatment. Twenty-four
      (89%) of 27 patients with internal nasal valve dysfunction reported improvement
      in nasal obstruction. Spreader grafts caused a widening of the middle third of
      the nose. Alar batten grafts resulted in effacement of deep alar creases and a
      widening of the nasal tip. CONCLUSIONS: We have found that surgical correction of
      nasal valve obstruction is extremely effective in improving subjective nasal
      obstruction. Success of this procedure is predicated by correct diagnosis and
      appropriate surgical technique.

PMID- 15148125
TI  - Quantitative analysis of lip appearance after V-Y lip augmentation.
AB  - OBJECTIVE: To quantitatively analyze the changes in the 3-dimensional appearance
      of the lips after V-Y lip advancement for lip augmentation. DESIGN: A
      retrospective single-blinded study of patients who had a V-Y lip augmentation
      from January 1999 to December 2001. Standardized anterior and lateral
      preoperative and postoperative digital photographs of patients were analyzed
      using digital imaging software to quantify postoperative changes. RESULTS: There
      were statistically significant increases in the vertical height of the upper red
      lip (75%) and in the area of the upper red lip (66%). The upper and lower lip
      projection increased by approximately 40%. The vertical distance from the apex to
      the trough of Cupid's bow increased by 56.7%. CONCLUSIONS: The V-Y lip
      advancement for lip augmentation increases the parameters that characterize the
      fullness of the upper lip and enhances the vermilion "pout" and projection of the
      upper and lower lip. It also increases the curvature of Cupid's bow.

PMID- 15148126
TI  - Toward an ideal lip augmentation procedure.

PMID- 15148127
TI  - Considerations in V-Y lip augmentation.

PMID- 15148128
TI  - Modeling aberrant wound healing using tissue-engineered skin constructs and
      multiphoton microscopy.
AB  - BACKGROUND: Keloids and hypertrophic scars result from aberrant wound healing and
      remain a potential complication of any surgical procedure or trauma.
      Investigation of aberrant wound healing has been limited to the study of growth
      factors, collagen precursors, and DNA synthesis in simple in vitro systems, which
      necessitate removal or destruction of cells or factors in the growth environment
      of cell cultures. Multiphoton microscopy (MPM) can use endogenous chromophores
      such as collagen and nicotinamide adenine dinucleotide hydrogenase to produce
      thin optical sections of thick living tissues without the use of dyes or stains.
      Endogenous second-harmonic-generation (SHG) signals in collagen can be collected
      to form an MPM image. OBJECTIVE: To present a novel wound-healing model used to
      investigate keloid-derived fibroblast activity and collagen production in the
      same intact tissue-engineered construct over time. METHODS: Artificial tissue
      constructs called RAFTs (produced by suspension of keloid or normal dermal
      fibroblasts in type I collagen gel with an overlying keratinocyte layer) were
      cultured at air-fluid interface. Multiphoton microscopy SHG images of collagen in
      the intact tissue constructs consisting of normal or keloid-derived fibroblasts
      were obtained. The constructs were then incised with a scalpel. Serial MPM and
      phase-contrast microscopy images were obtained to monitor changes in the
      extracellular matrix in response to wounding of the artificial skin construct
      over 8 days. RESULTS: The tissue-engineered constructs formed a bilayer
      resembling the dermis and epidermis of human skin. Phase-contrast microscopy
      revealed migration of keratinocytes into the defect created by scalpel wounding.
      The constructs were found to contract with time after wounding. The MPM SHG
      images showed collagen deposition in the tissue constructs after wounding. Tissue
      constructs with keloid-derived fibroblasts were found to deposit collagen at a
      higher rate than those with normal fibroblasts. CONCLUSIONS: The MPM model
      described herein permits serial observation of the same intact specimens without
      the need for fixation or cytotoxic stains. Furthermore, it demonstrates the
      biologic activity of RAFT artificial tissue constructs.

PMID- 15148129
TI  - Botulinum toxin for masseter reduction in Asian patients.
AB  - Asian patients frequently seek aesthetic alteration of hypertrophic masseter
      muscles to reduce a prominent mandibular angle. Surgical reduction is common in
      Asia, but botulinum toxin offers a less invasive approach. This pilot study
      evaluated results of aesthetic lower face narrowing in 20 Asian patients.
      Initially, 25 U of botulinum toxin (5 U/0.1 mL) was injected at each inferior
      masseter border; an additional 25 U was injected per side as needed at 1-week
      intervals. Seven patients (35%) required only 1 injection; 10 (50%) required 2;
      and 3 (15%) required 3 injections. Maximum reduction was seen at 1 to 2 months;
      more prominent hypertrophy yielded the most impressive results. Maintenance
      reinjection took place at 6 to 8 months. Up to 12 months of follow-up is reviewed
      herein. Two patients (10%) complained of mild fatigue after vigorous chewing and
      1 developed mild transient buccal weakness. Nineteen of 20 patients were
      satisfied.

PMID- 15148130
TI  - Immediate autogenous cartilage grafts in rhinoplasty after alloplastic implant
      rejection.
AB  - BACKGROUND: It is accepted in rhinoplasty that complications are more common with
      alloplastic implants than with autografts. There is little guidance in the
      literature on how to deal with the cosmetic and/or functional problems that
      follow alloplastic implant rejection. The conventional advice has been to remove
      the allograft and not place any graft at the same time. The present article
      presents our experience treating allograft rejection and immediately repairing
      any structural defect with autografts. OBJECTIVE: To demonstrate that immediate
      nasal reconstruction using autogenous cartilage is a good technique when an
      alloplastic material has to be removed because of rejection, inflammation, or
      infection. DESIGN: A retrospective analysis of outcome for a case series.
      METHODS: A retrospective review of the management of 8 patients who presented to
      2 tertiary referral centers with alloplastic implant rejection following
      rhinoplasty. In 7 cases, the alloplastic implant had to be removed because it had
      migrated and caused a foreign body reaction; in 1 case, the implant had caused a
      bacterial infection. RESULTS: In all 8 cases, the nasal deformity that followed
      the removal of the allograft was so marked that the nose was immediately
      reconstructed with autogenous cartilage. The patients all made a good recovery
      after immediate reconstruction, although skin changes associated with the
      alloplastic implant remained after a mean follow-up of 3 years 3 months.
      CONCLUSION: The use of autogenous cartilage is a good option for nasal
      augmentation immediately after the removal of an alloplastic implant.

PMID- 15148131
TI  - Multivectored suture suspension: a minimally invasive technique for reanimation
      of the paralyzed face.
AB  - BACKGROUND: Despite advanced techniques for reanimation of the lower face, many
      patients opt for static suspension procedures, which are less invasive and have a
      relatively short recovery period. However, even static suspension procedures
      require general anesthesia, overnight hospital stay, and significant soft tissue
      manipulation. We present a minimally invasive technique, the multivectored suture
      suspension, which addresses these drawbacks. OBJECTIVES: To study the technical
      feasibility and efficacy of the multivectored suture suspension technique in the
      paralyzed face. DESIGN: The study was carried out prospectively in 12 patients
      with House-Brackmann grade 6 facial paralysis. Nine patients presented within 6
      months of tumor resection and 3 patients presented more than 1 year after
      surgery. MAIN OUTCOME MEASURES: The parameters evaluated were (1). restoration of
      nasal breathing; (2). improvement of drooling; (3). restoration of normal speech;
      (4). cosmetic results; and (5). total surgical time. RESULTS: With an average
      follow-up of 14 months, patient evaluation of the outcome parameters was as
      follows: (1). 10 patients (83%) reported significant and 2 (17%) reported
      moderate restoration of nasal breathing; (2). 10 patients (83%) reported
      significant improvement and 2 (17%) reported modest drooling improvement; (3). 8
      patients (66%) reported significant improvement and 4 (34%) reported modest
      improvement of speech; (4). 9 patients (75%) reported complete satisfaction and 3
      (25%) reported moderate satisfaction with cosmesis. The average surgical time was
      46 minutes. Three revisions were required for suture failure. CONCLUSIONS: The
      multivectored suture suspension technique is a minimally invasive, reversible
      method of lower facial reanimation that provides improved cosmesis with
      restoration of nasal breathing. It can be performed under local anesthesia in an
      outpatient setting, thereby reducing morbidity and cost.

PMID- 15148132
TI  - Closure of conchal cartilage harvest sites via absorbable quilting suture.

PMID- 15148133
TI  - Severe granulomatous inflammatory response induced by injection of polyacrylamide
      gel into the facial tissue.
AB  - Facial soft tissue augmentation has been performed using different materials. We
      describe a woman who received polyacrylamide gel injections for cosmetic reasons
      and developed a severe granulomatous inflammation paranasally. Because the
      patient did not mention the cosmetic intervention, the diagnosis of
      polyacrylamide gel-induced granuloma was complicated. The distinctive
      histopathological findings led to the correct diagnosis despite sparse clinical
      information. Since complete surgical excision was not feasible, she was treated
      with repeated multiple local injections of triamcinolone acetonide.
      Polyacrylamide gel may have favorable properties for facial tissue augmentation,
      but a severe granulomatous inflammatory response induced by injection of
      polyacrylamide gel may occur. Before treatment with polyacrylamide gel injection
      this complication should be disclosed to the patient.

PMID- 15148134
TI  - Toward a global beauty: the art of Cai Guo-Qiang.

PMID- 15148135
TI  - Serum copper: a biomarker for Alzheimer disease?

PMID- 15148136
TI  - Levodopa elevates homocysteine: is this a problem?

PMID- 15148137
TI  - Genetic basis of developmental malformations of the cerebral cortex.
AB  - Widespread use of noninvasive brain imaging techniques, in particular magnetic
      resonance imaging, has led to increased recognition of genetic disorders of
      cortical development in recent years. The causative genes for many of these
      disorders have been identified through a combination of detailed clinical and
      radiological analyses and molecular genetic approaches. These disease genes have
      been found to affect different steps of cortical development, including
      proliferation of neuronal progenitor cells, neuronal migration, and maintaining
      integrity of the pial surface. In many cases, syndromes with similar clinical
      phenotypes are caused by genes with related biochemical functions. In this
      article, we review the recent advances in molecular genetic studies of the
      disorders of cortical development. The identification and functional studies of
      the genes associated with these developmental disorders will likely lead to
      improvement in diagnosis and facilitate our understanding of the mechanisms of
      cortical development.

PMID- 15148138
TI  - The neurobiology of dopamine signaling.
AB  - The brain contains 2 major groups of dopamine neurons. One is located in the
      arcuate nucleus of the hypothalamic median eminence and is involved in
      neuroendocrine regulation. The other, which is the subject of this article, is
      located in the ventral mesencephalon and projects to the forebrain. Although
      dopamine neurons are few (<1/100 000 brain neurons), they play an important role
      in regulating several aspects of basic brain function. They are necessary for the
      normal tasks of the regions they innervate, including motor behavior, motivation,
      and working memory. Dopamine neurons are also a central element in the brain
      reward system that controls the learning of many behaviors. Disappearance of
      nigrostriatal neurons results in Parkinson disease, whereas blockade of dopamine
      receptors has therapeutic effects in psychosis. Finally, artificial increase in
      dopamine transmission is the common mechanism of action of drugs of abuse that
      leads to addiction. Understanding how dopamine works is a major goal of
      neurobiology. Much progress has been accomplished in identifying the
      intracellular signaling pathways that underlie the immediate actions of dopamine
      and account for its long-term effects on brain properties. Recent findings allow
      us to identify molecules that may represent future therapeutic targets in
      neurology and psychiatry.

PMID- 15148139
TI  - Therapy for nerve agent poisoning.
AB  - Neurologists need to familiarize themselves with nerve agents, the most toxic of
      the chemical warfare agents. Their mode of action lies within the nervous system,
      and nonneurologists will look to neurologists for expert advice on therapy. These
      agents cause rapid-onset cholinergic crisis amenable to prompt treatment with
      specific antidotes. Experience on the battlefield and in terrorist attacks
      demonstrates that therapy saves lives.

PMID- 15148140
TI  - Levodopa-associated increase of homocysteine levels and sural axonal
      neurodegeneration.
AB  - BACKGROUND: Levodopa metabolism via catechol O-methyltransferase increases levels
      of the neurotoxin homocysteine, which induces an axonal-accentuated degeneration
      in sensory peripheral nerves in vitro. OBJECTIVES: To demonstrate associations
      among daily levodopa/dopa decarboxylase inhibitor intake, total homocysteine
      plasma (tHcy) levels, and electrophysiologic sural nerve conduction findings.
      DESIGN: We performed bilateral assessment of sensory nerve conduction velocity
      and sensory nerve action potentials and determined tHcy levels. PATIENTS: Thirty
      one levodopa-treated patients with Parkinson disease (PD) and 27 control
      subjects. RESULTS: Sensory nerve action potentials significantly (P<.001)
      differed between PD patients and controls. No differences between sensory nerve
      conduction velocities of PD patients and controls appeared. We found significant
      differences in sensory nerve action potentials be-tween PD patients with
      significantly elevated tHcy levels and controls (P<.001), PD patients with tHcy
      levels within the reference range and those with elevated levels (P =.001), and
      PD patients with tHcy levels levels within the reference range and and controls
      (P =.04). Our sensory nerve conduction velocity results showed no significant
      differences. There were significant associations between tHcy levels and sensory
      nerve action potentials (R = -0.52; P =.002) and and sensory nerve conduction
      velocity (R = -0.47; P =.008). Daily levodopa/dopa decarboxylase inhibitor intake
      was significantly related to tHcy levels (R = 0.43; P =.02). CONCLUSIONS: This
      electrophysiological sign of peripheral neuronal dysfunction may be
      circumstantial evidence suggesting that, to a certain extent, sensory nerve
      action potentials are a surrogate marker for the levodopa metabolism-induced
      elevation of homocysteine levels and the aggravation of the ongoing central
      neurodegenerative process.

PMID- 15148141
TI  - Diabetes mellitus and risk of Alzheimer disease and decline in cognitive
      function.
AB  - BACKGROUND: Few prospective studies have assessed diabetes mellitus as a risk
      factor for incident Alzheimer disease (AD) and decline in cognitive function.
      OBJECTIVE: To evaluate the association of diabetes mellitus with risk of AD and
      change in different cognitive systems. DESIGN: Longitudinal cohort study.
      PARTICIPANTS: For up to 9 years, 824 older (those >55 years) Catholic nuns,
      priests, and brothers underwent detailed annual clinical evaluations. MAIN
      OUTCOME MEASURES: Clinically diagnosed AD and change in global and specific
      measures of cognitive function. RESULTS: Diabetes mellitus was present in 127
      (15.4%) of the participants. During a mean of 5.5 years of observation, 151
      persons developed AD. In a proportional hazards model adjusted for age, sex, and
      educational level, those with diabetes mellitus had a 65% increase in the risk of
      developing AD compared with those without diabetes mellitus (hazard ratio, 1.65;
      95% confidence interval, 1.10-2.47). In random effects models, diabetes mellitus
      was associated with lower levels of global cognition, episodic memory, semantic
      memory, working memory, and visuospatial ability at baseline. Diabetes mellitus
      was associated with a 44% greater rate of decline in perceptual speed (P =.02),
      but not in other cognitive systems. CONCLUSIONS: Diabetes mellitus may be
      associated with an increased risk of developing AD and may affect cognitive
      systems differentially.

PMID- 15148142
TI  - Inflammatory proteins in plasma and the risk of dementia: the rotterdam study.
AB  - BACKGROUND: Increased levels of inflammatory proteins have been found in the
      brains and plasma samples of patients with dementia. Whether the levels of
      inflammatory proteins in plasma samples are elevated before clinical onset of
      dementia is unclear. OBJECTIVE: To determine whether high levels of inflammatory
      proteins in plasma samples are associated with an increased risk of dementia.
      DESIGN AND SETTING: A case-cohort study within the Rotterdam Study, a population
      based prospective cohort study in the Netherlands. PARTICIPANTS: The source
      population comprises 6713 subjects who, at baseline (1990-1993), were free of
      dementia and underwent venipuncture. From these, we selected both a random
      subcohort of 727 subjects and 188 cases who had developed dementia at follow-up.
      MAIN OUTCOME MEASURES: The associations between plasma levels of alpha1
      antichymotrypsin, C-reactive protein, interleukin 6, the soluble forms of
      intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and the
      risk of dementia were examined using the Cox proportional hazards regression
      models. RESULTS: High levels of alpha1-antichymotrypsin, interleukin 6, and, to a
      lesser extent, C-reactive protein were associated with an increased risk of
      dementia; rate ratios per standard deviation increase were 1.49 (95% confidence
      interval, 1.23-1.81), 1.28 (95% confidence interval, 1.06-1.55), and 1.12 (95%
      confidence interval, 0.99-1.25), respectively. Similar associations were observed
      for Alzheimer disease, whereas rate ratios of vascular dementia were higher for
      alpha1-antichymotrypsin and C-reactive protein. Soluble forms of intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 were not associated
      with dementia. CONCLUSION: Plasma levels of inflammatory proteins are increased
      before clinical onset of dementia, Alzheimer disease, and vascular dementia.

PMID- 15148143
TI  - The AED (antiepileptic drug) pregnancy registry: a 6-year experience.
AB  - BACKGROUND: Pregnancy registries are a new method for assessing the fetal risks
      from exposures in pregnancy. We present the findings of the North American AED
      (antiepileptic drug) Pregnancy Registry for phenobarbital sodium-exposed
      pregnancies. OBJECTIVE: To determine whether exposure during pregnancy to
      anticonvulsant drugs as monotherapy, and phenobarbital in particular, is
      associated with an increased risk of major malformations in comparison with
      unexposed controls. DESIGN: Evaluation of registry data. SETTING: The North
      American AED Pregnancy Registry. PATIENTS: Pregnant women throughout the United
      States and Canada who were taking an anticonvulsant drug and who called a toll
      free telephone number to enroll. INTERVENTIONS: Each woman was interviewed by
      telephone at enrollment, at 7 months' gestation, and post partum. With the
      mother's written permission, her medical records and those of her infant were
      obtained. MAIN OUTCOME MEASURES: Major malformations identified by 5 days of age.
      Criteria for the release of findings were established by the independent
      Scientific Advisory Committee on the basis of malformations identified in infants
      of women who had enrolled prospectively before having had any prenatal screening
      ("pure" enrollees). RESULTS: Five (6.5%) of 77 pure pregnancies with exposure to
      phenobarbital monotherapy were associated with major malformations (95%
      confidence interval of proportion, 2.1%-14.5%). When compared with the background
      rate (1.62%), there was a significantly increased risk (relative risk, 4.2; 95%
      confidence interval, 1.5-9.4). CONCLUSIONS: A hospital-based pregnancy registry
      can establish the fetal risk of major malformations for a commonly used drug.
      Prenatal exposure to phenobarbital is associated with a significantly increased
      risk of fetal abnormalities.

PMID- 15148145
TI  - Extreme variability of phenotype in patients with an identical missense mutation
      in the lamin A/C gene: from congenital onset with severe phenotype to milder
      classic Emery-Dreifuss variant.
AB  - BACKGROUND: Mutations of the LMNA gene, encoding the nuclear envelope proteins
      lamins A and C, have been associated with 7 distinct pathologic conditions.
      OBJECTIVE: To report 5 cases with the same missense mutation in exon 6 of the
      LMNA gene, resulting in an E358K substitution in the central rod domain. DESIGN:
      Case report. SETTING: Three muscle centers in England. PATIENTS: Five patients
      with missense mutations of the LMNA gene. RESULTS: All 5 individuals had muscle
      involvement, but the onset, severity, distribution of muscle weakness, and
      presence of associated features were highly variable. Three patients had
      humeroperoneal distribution of weakness and typical features of Emery-Dreifuss
      muscular dystrophy. Two other patients showed additional novel features. One had
      congenital onset and predominant axial weakness, with poor neck control and
      inability to sit independently at the age of 21 months. Another patient presented
      in childhood with an unusual pattern of muscle weakness, short stature, and
      midface hypoplasia with striking fat accumulation around the face and neck, in
      contrast to wasting of adipose tissue and muscle in the limbs. She developed both
      respiratory failure and cardiac arrhythmias in her late 20s. CONCLUSION: Our
      cases expand the clinical spectrum associated with mutations in the LMNA gene and
      further illustrate the overlapping phenotypes of the laminopathies.

PMID- 15148144
TI  - Quality of life is favorable for most patients with multiple sclerosis: a
      population-based cohort study.
AB  - BACKGROUND: Quality of life (QOL) is becoming an increasingly important factor in
      measurement of disease impact as well as an outcome measure in clinical trials.
      OBJECTIVES: To study the QOL of patients with multiple sclerosis (MS) in a
      population-based prevalence cohort and compare it with the general US population.
      DESIGN: Population-based prevalence cohort. SETTING: Olmsted County, Minn,
      population. PARTICIPANTS: All patients with definite MS (N = 201) alive and
      residing in Olmsted County on December 1, 2000. INTERVENTION: None. MAIN OUTCOME
      MEASURES: The expanded disability status scale (EDSS) and the Multiple Sclerosis
      Quality of Life Health Survey (MSQOL-54), which consisted of Short Form 36 (SF
      36) with an additional 18 items pertinent to MS. RESULTS: The MSQOL-54 form was
      completed by 185 patients. Patients with MS had worse scores than the general US
      population with respect to physical functioning, vitality, and general health
      dimensions of the SF-36 QOL measure. Many QOL domains (pain, role emotional,
      mental health, and social functioning) were, however, similar for the 2000 MS
      cohort compared with the general US population. Duration of MS and EDSS score
      correlated significantly with physical functioning (P<.001). The QOL correlation
      with EDSS score was less than expected. No significant difference in the scores
      for the 8 QOL dimensions were found for patients with quick vs slow progression
      (quick progression defined as <5 years from onset to EDSS score of 3). The
      majority of patients with MS (77%) were mostly satisfied or delighted with their
      QOL. CONCLUSION: Though MS can cause significant disability, most patients with
      MS in the Olmsted County prevalence cohort continue to report a good QOL.

PMID- 15148146
TI  - Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility
      but impairs response inhibition in Parkinson disease.
AB  - BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) improves
      motor symptoms of Parkinson disease. Although several studies have assessed
      cognitive functions before surgery and after long-term STN stimulation, only a
      few have assessed patients while stimulation is on and off to more specifically
      address the short-term cognitive effects of STN deep brain stimulation.
      OBJECTIVE: To examine the short-term effects of STN stimulation on several tests
      sensitive to executive function and the long-term effects of STN stimulation on a
      global cognitive scale. DESIGN: Twenty-three patients with Parkinson disease were
      tested 6 to 12 months after surgery with STN stimulation switched on and off in a
      random order while taking their regular medication. The Unified Parkinson's
      Disease Rating Scale motor score was also rated in the on and off stimulation
      condition. The neuropsychological battery included digit span, verbal fluency,
      Stroop color test, and random number generation in a single- and dual-task
      condition. RESULTS: Short-term stimulation improved the results on the Random
      Number Generation Task, requiring suppression of habitual responses, but induced
      more errors in the interference task of the Stroop color test. Digit span, verbal
      fluency, and dual-task performance results did not change. There was a
      significant correlation (r = 0.47, P =.02) between improved performance on the
      Random Number Generation Task and impaired response inhibition in the Stroop
      interference condition. A preoperative to postoperative comparison showed no
      changes in global cognitive function with long-term STN deep brain stimulation.
      CONCLUSIONS: Short-term STN stimulation improves cognitive flexibility (giving up
      habitual responses) but impairs response inhibition. Long-term STN stimulation
      does not change global cognitive function.

PMID- 15148147
TI  - Clinical findings in a large family with a parkin ex3delta40 mutation.
AB  - OBJECTIVE: To describe a large consanguineous family in which inheritance of a
      438- to 477-base pair deletion in exon 3 (Ex3Delta40) in the parkin gene resulted
      in parkinsonism (age range at onset, 24-32 years). DESIGN: Fifty-two family
      members underwent genetic analysis. MAIN OUTCOME MEASURE: Two clinical examiners
      blinded to genetic status evaluated 21 family members, including all mutation
      carriers (4 homozygous and 12 heterozygous individuals; 5 family members did not
      have the mutation). RESULTS: In this family, the parkin Ex3Delta40 mutation is
      recessive; only homozygotes manifest symptoms of early-onset levodopa-responsive
      parkinsonism, including resting tremor, dystonia, and slow progression, with the
      caveat that presymptomatic signs of dopaminergic loss in heterozygotes must be
      excluded by fluorodopa F 18 with positron emission tomography. This contrasts
      with the autosomal dominant pattern of inheritance of parkinsonism described in
      families with the same mutation. CONCLUSION: In families with a dominant
      inheritance, an additional genetic or environmental cause must coexist with the
      Ex3Delta40 mutation.

PMID- 15148149
TI  - Cerebrospinal fluid tau protein and periventricular white matter lesions in
      patients with mild cognitive impairment: implications for 2 major pathways.
AB  - BACKGROUND: Mild cognitive impairment (MCI) may be a heterogeneous condition
      rather than a uniform disease entity. OBJECTIVE: To develop reliable tools that
      aid in identifying patients at risk of developing Alzheimer disease (AD) among
      heterogeneous populations with MCI to maximize the benefits of emerging therapies
      for AD. DESIGN: A 2-year prospective study. SETTING: Clinical follow-up in an
      outpatient memory clinic. PATIENTS: Seventy-two consecutive older patients with
      memory complaints. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau levels,
      severity of periventricular and deep white matter lesions, silent brain
      infarction on magnetic resonance imaging, plasma homocysteine levels,
      apolipoprotein E genotype, and other vascular risk factors were assessed at
      baseline. RESULTS: Fifty-seven patients were diagnosed as having amnestic MCI.
      Forty-one patients with (AD-converted MCI group) or without (progressive MCI
      group) conversion to dementia and AD progressed over time, whereas the other 16
      patients remained cognitively stable (stable MCI group). The stable MCI group was
      characterized by normal cerebrospinal fluid tau levels and a high grade of
      periventricular white matter lesions (PWMLs). The progressive MCI and AD
      converted MCI groups had increased cerebrospinal fluid tau levels and low grades
      of PWMLs. A logistic regression model showed that age was significantly
      associated with developing PWMLs (P =.03; odds ratio, 1.15; 95% confidence
      interval, 1.0-1.3). CONCLUSIONS: Tau-related AD pathologic conditions and
      possibly ischemic PWMLs represent 2 major etiologies in the development of MCI,
      reflecting heterogeneity in the clinical progression. Because the progressive
      type of MCI may be a primary target of clinical trials that aim at secondary
      prevention of dementia, these patients should be identified by appropriate
      biomarkers and neuroimaging techniques.

PMID- 15148148
TI  - Relation of plasma lipids to Alzheimer disease and vascular dementia.
AB  - BACKGROUND: The relation between plasma lipid levels and Alzheimer disease (AD)
      and vascular dementia (VaD), and the impact of drugs to lower lipid levels
      remains unclear. OBJECTIVE: To investigate the relation between plasma lipid
      levels and the risk of AD and VaD and the impact of drugs to lower lipid levels
      on this relationship. DESIGN AND SETTING: Cross-sectional and prospective
      community-based cohort studies. PARTICIPANTS: Random sample of 4316 Medicare
      recipients, 65 years and older, residing in northern Manhattan, NY. MAIN OUTCOME
      MEASURES: Vascular dementia and AD according to standard criteria. RESULTS:
      Elevated levels of non-high-density lipoprotein (HDL-C) and low-density
      lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk
      factors for VaD in either cross-sectional or prospective analyses. Higher levels
      of total cholesterol were associated with a decreased risk of incident AD after
      adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk
      factors. Treatment with drugs to lower lipid levels did not change the disease
      risk of either disorder. CONCLUSIONS: We found a weak relation between non-HDL-C,
      LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents
      to lower them do not seem to be associated with the risk of AD.

PMID- 15148150
TI  - Pituitary volume and headache: size is not everything.
AB  - BACKGROUND: Pituitary tumors are commonly associated with disabling headache. The
      accepted mechanisms for headache are dural stretch and cavernous sinus invasion.
      OBJECTIVE: To determine if there is a relationship between pituitary tumor size
      and the report of headache. DESIGN: We prospectively studied 63 patients who were
      initially seen with pituitary tumors. Clinical headache scores, pituitary tumor
      volume, and the extent of cavernous sinus invasion were obtained for each
      patient. RESULTS: The prevalence of headache was 70%. There was no positive
      correlation the between clinical headache score and pituitary volume (r = -0.32,
      P =.01, Spearman rank correlation). There was also no association between
      cavernous sinus invasion and headache. There was a strong association between
      pituitary-associated headache and a family history of headache (chi(2) = 8.36, P
      =.004). CONCLUSIONS: These data suggest that a pituitary tumor-associated
      headache may not simply be a structural problem. Other factors such as family
      history of headache, and the endocrine activity of the tumor may be equally
      important determinants of headache. Elucidating these mechanisms will aid in the
      treatment of these patients and further our understanding of other headache
      syndromes.

PMID- 15148151
TI  - Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of
      spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225
      Italian families.
AB  - BACKGROUND: Autosomal dominant cerebellar ataxias are a clinical and genetically
      heterogeneous group of progressive neurodegenerative diseases, at present
      associated with 22 loci (spinocerebellar ataxia [SCA] 1-SCA8, SCA10-SCA19, SCA21,
      SCA22, fibroblast growth factor 14 [FGF14]-SCA, and dentatorubral-pallidoluysian
      atrophy [DRPLA]). The relevant gene has been identified in 12 cases (SCA1-3, SCA6
      8, SCA10, SCA12, FGF14, and DRPLA), and in all but the recently identified SCA14,
      SCA17, PRKCG and FGF14 genes, the defect consists of the expansion of a short
      nucleotide repeat. OBJECTIVES: To investigate the relative prevalence of SCA1-3,
      SCA6-8, SCA10, SCA12, and SCA17 gene expansions in Italian families with
      hereditary ataxia, specifically to verify the occurrence of SCA10, SCA12, and
      SCA17 in Italy; and to analyze samples from probands with negative test results
      at the initial screening by means of the repeat expansion detection technique to
      identify CAG/CTG expansions in novel loci.Patients Two hundred twenty-five
      unrelated Italian index cases with hereditary ataxia, most (n = 183) of whom
      presented with a clear dominantly transmitted trait. RESULTS: We found that SCA1
      and SCA2 gene mutations accounted for most cases (21% and 24%, respectively). We
      found SCA3, SCA6, SCA7, SCA8, and SCA17 to be very rare (approximately 1% each),
      and no case of SCA10 or SCA12 was identified. Half of the index cases (113/225)
      were negative for expansions in the known SCA genes. Repeat expansion detection
      analysis performed on 111 of these cases showed a CAG/CTG repeat expansion of at
      least 50 triplets in 22 (20%). Twenty-one of 22 expansions could be attributed to
      length variation at 2 polymorphic loci (expanded repeat domain CAG/CTG 1 [ERDA1]
      or CTG repeat on chromosome 18q21.1 [CTG18.1]). In 1 patient, the expansion was
      assigned to the DRPLA gene. CONCLUSIONS: The distribution of SCA1-3 and SCA6-7
      gene mutations is peculiar in Italy. We found a relatively high frequency of SCA1
      and SCA2 gene expansions; SCA3, SCA6, and SCA7 mutations were rare, compared with
      other European countries. No SCA10 or SCA12 and only a few SCA8 (2/225) and SCA17
      (2/225) families were detected. In patients negative for defects in known SCA
      genes, repeat expansion detection data strongly suggest that, at least in our
      population, CAG/CTG expansions in novel genes should be considered an unlikely
      cause of the SCA phenotype.

PMID- 15148153
TI  - Pathologic prion protein spreading in the peripheral nervous system of a patient
      with sporadic Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Involvement of the peripheral nervous system in the pathogenesis of
      prion diseases is becoming increasingly evident. However, pathologic protease
      resistant prion protein deposition in the peripheral nerves of patients with
      Creutzfeldt-Jakob disease has never been demonstrated, to our knowledge.
      OBJECTIVE: To determine whether mutated prion protein accumulation could be shown
      in the peripheral nervous system of patients with sporadic Creutzfeldt-Jakob
      disease. DESIGN: Autopsy study. PATIENTS: Three patients with sporadic
      Creutzfeldt-Jakob disease. INTERVENTIONS: Study of the brain, spinal cord, and
      sciatic and superficial peroneal nerves by immunohistochemistry and Western blot
      analysis. MAIN OUTCOME MEASURE: Demonstration of protease-resistant prion protein
      accumulation. RESULTS: In all cases, protease-resistant prion protein
      accumulation was found in the brain and posterior horns of the spinal cord. In 1
      case, protease-resistant prion protein deposits were also evidenced in the dorsal
      root ganglia and the superficial peroneal nerve. CONCLUSIONS: Protease-resistant
      prion protein may be found in the peripheral nervous system of some patients with
      sporadic Creutzfeldt-Jakob disease. However, a larger series is required to
      assess the incidence of peripheral nervous system involvement and to discuss the
      diagnostic usefulness of peripheral nerve biopsy in sporadic Creutzfeldt-Jakob
      disease.

PMID- 15148152
TI  - Copper perturbation in 2 monozygotic twins discordant for degree of cognitive
      impairment.
AB  - BACKGROUND: Recent evidence indicates that peripheral tissue markers can provide
      information regarding changes affecting cellular metabolism in Alzheimer disease
      (AD). We previously reported that serum copper levels can discriminate subjects
      with AD from normal control subjects (with 60% sensitivity and 95% specificity)
      and from patients with vascular dementia (with 63% sensitivity and 85%
      specificity). OBJECTIVE: To study the correlation between AD and serum levels of
      transition metals and markers of peripheral oxidative stress. DESIGN: Case study.
      SETTING: General hospital inpatient wards and outpatient clinics. Patients A pair
      of elderly monozygotic female twins discordant for AD. MAIN OUTCOME MEASURES:
      Biochemical analyses of peripheral-blood transition metals and indicators of
      oxidative stress and neurologic and neuropsychological assessments of clinical
      status for presence of cognitive impairment and AD. RESULTS: Serum copper and
      total peroxide levels were both 44% higher in the twin with greater cognitive
      impairment and a diagnosis of AD. CONCLUSIONS: The cases reported support the
      hypothesis of a major involvement of copper and oxidative abnormalities in AD.

PMID- 15148154
TI  - Dementia-like presentation of striatal hypermetabolic state with antistriatal
      antibodies responsive to steroids.
AB  - BACKGROUND: Hypermetabolic lesions of the striatum are rare. They usually involve
      autoimmunity and are associated with choreatic disorders such as Sydenham chorea,
      lupus, and the antiphospholipid antibody syndrome. PATIENT: A 48-year-old woman
      was initially seen with a 1-year history of progressive changes in personality
      and attention. There were minor associated involuntary movements. Negative
      routine investigation results, including regular autoimmune serologies and
      magnetic resonance imaging, led to the diagnosis of a frontal dementia. Positron
      emission tomographic results demonstrated hypermetabolism in the left striatum.
      Western blot technique results demonstrated plasma antistriatal antibodies.
      Treatment with corticosteroids induced a resolution of her attentional deficits
      and a return of her personality to its premorbid state. The repeated positron
      emission tomographic scan results were near normal, and the titer of antistriatal
      antibodies was significantly reduced. CONCLUSION: Autoimmune striatal dysfunction
      can initially appear with a clinical picture suggestive of a degenerative
      dementia. Recognition of the underlying etiology and treatment was possible
      because of abnormalities uncovered on positron emission tomographic images.

PMID- 15148155
TI  - Narcolepsy caused by acute disseminated encephalomyelitis.
AB  - BACKGROUND: Narcolepsy with cataplexy is caused by a selective loss of hypocretin
      producing neurons, but narcolepsy can also result from hypothalamic and rostral
      brainstem lesions. PATIENT: We describe a 38-year-old woman with severe daytime
      sleepiness, internuclear ophthalmoplegia, and bilateral delayed visual evoked
      potentials. Her multiple sleep latency test results demonstrated short sleep
      latencies and 4 sleep-onset rapid eye movement sleep periods, and her
      cerebrospinal fluid contained a low concentration of hypocretin. Magnetic
      resonance imaging showed T2 and fluid-attenuated inversion recovery
      hyperintensity along the walls of the third ventricle and aqueduct, which are
      consistent with acute disseminated encephalomyelitis. RESULTS: After treatment
      with steroids, this patient's subjective sleepiness, hypersomnia, and hypocretin
      deficiency partially improved. CONCLUSIONS: Autoimmune diseases such as acute
      disseminated encephalomyelitis can produce narcolepsy. Most likely, this
      narcolepsy is a consequence of demyelination and dysfunction of hypocretin
      pathways, but direct injury to the hypocretin neurons may also occur.

PMID- 15148156
TI  - Copper deficiency myelopathy.
AB  - BACKGROUND: In humans, Menkes disease is the well-recognized neurological
      disorder due to inherited copper deficiency. Myelopathy due to acquired copper
      deficiency is not a well-recognized entity in humans, although myelopathy due to
      copper deficiency is well documented in some animal species. PATIENTS: We
      describe 3 patients who developed a progressive spastic-ataxic gait with
      proprioceptive deficits. All patients had a severe reduction in serum
      ceruloplasmin and copper levels. RESULTS: All patients had evidence of posterior
      column dysfunction clinically and on somatosensory evoked potential studies. Two
      had a signal change in the posterior column on magnetic resonance imaging of the
      spinal cord. CONCLUSION: Patients presenting with otherwise unexplained
      myelopathies should have their serum ceruloplasmin level measured.

PMID- 15148157
TI  - Multilevel intramedullary spinal neurocysticercosis with eosinophilic meningitis.
AB  - BACKGROUND: Cysticercal involvement of the spinal cord is a very rare form of
      neurocysticercosis. Intramedullary cysts are even less common. OBJECTIVE: To
      describe a novel presentation of multilevel intramedullary neurocysticercosis
      with eosinophilic meningitis. DESIGN: Case report. PATIENT: A 35-year-old man
      with a history of cerebral neurocysticercosis who presented with both cauda
      equina and Brown-Sequard syndromes associated with cerebrospinal fluid findings
      of eosinophilic meningitis. RESULTS: Magnetic resonance imaging confirmed the
      multilevel intramedullary cord lesions. The patient was treated medically with
      dexamethasone and albendazole and had a good recovery. CONCLUSION: Intramedullary
      neurocysticercosis should be considered as a potentially treatable cause of
      multilevel spinal lesions with subacute meningitis.

PMID- 15148158
TI  - "Hyperechogenic rim" sign in internal carotid artery thrombus.

PMID- 15148159
TI  - Wernicke encephalopathy.

PMID- 15148160
TI  - Babinski's clinical differentiation of organic paralysis from hysterical
      paralysis: effect on US neurology.
AB  - BACKGROUND: The formalized neurological examination developed near the end of the
      19th century, and clinicians searched for signs to differentiate weakness due to
      structural lesions of the central nervous system (organic paralysis) from
      weakness caused by hysteria. Joseph F. F. Babinski worked in the shadow of his
      mentor, Jean M. Charcot, until 1893, but then developed independent studies to
      examine patients with both types of weakness. OBJECTIVES: To elucidate the role
      of Babinski in differentiating organic paralysis from hysterical paralysis and to
      describe his influence on 2 US neurologists, Charles Gilbert Chaddock and Charles
      Franklin Hoover. DESIGN: Primary and secondary sources were studied to outline
      the discoveries of Babinski and to determine his influence on US neurology.
      RESULTS: Babinski described toe extension in cases of organic paralysis and
      specifically stated that this sign did not occur in cases of hysterical
      paralysis. Chaddock and Hoover were influenced by the work of Babinski and
      disseminated his discoveries to US neurologists, each developing additional
      techniques to differentiate the 2 forms of paralysis. Each considered his
      technique superior to the Babinski toe sign. CONCLUSIONS: Although Babinski was
      only modestly appreciated by his contemporary peers of French neurology, his
      influence on US neurology was substantial. The Babinski, Chaddock, and Hoover
      signs that demonstrate whether structurally related upper motor neuron weakness
      exists continue to be useful maneuvers in separating these forms of paralysis
      from psychogenic weakness.

PMID- 15148161
TI  - Was the ataxia of Pierre Marie Machado-Joseph disease?: A reappraisal based on
      the last autopsy case from la Salpetriere Hospital.
AB  - Nosological placement of l'heredo-ataxie cerebelleuse de Pierre Marie (HAC) has
      never been established even after several autopsy cases from the original
      Haudebourg family had been reported. To reappraise the clinical and pathological
      features of HAC in the current framework of hereditary ataxias, we screened the
      autopsy records of la Salpetriere hospital and identified a patient with a
      diagnosis of HAC who underwent an autopsy in 1943. Clinical features included
      heredity compatible with autosomal dominant inheritance, spasticity, increased
      tendon reflexes, mask-like face, visual impairment, nuclear ophthalmoparesis, and
      exophthalmos in addition to progressive ataxia. Pathological lesions included the
      spinal cord (spinocerebellar tracts, anterolateral fascicles, and posterior
      column), cerebellar dentate nucleus, pontine nucleus, pallidum, motor neurons
      including the oculomotor nucleus, and substantia nigra. The cerebellar cortex and
      inferior olives were preserved. These clinical and pathological features, similar
      to those described in patients from the Haudebourg family, a core prototype of
      HAC, are indistinguishable from those of Machado-Joseph disease. It would then be
      possible to conclude that some of the patients historically considered to have
      HAC would today be classified as having Machado-Joseph disease.

PMID- 15148162
TI  - The aura-headache connection in migraine: a historical analysis.
AB  - A historical analysis is presented of insights into the pathogenetic mechanisms
      related to the migraine aura and headache and how the mechanisms connect. In the
      traditional sequential concept, advanced through the work of Edward Liveing, MD,
      Harold G. Wolff, MD, and others, the mechanisms are considered causally
      connected. A noncausal, parallel concept has been proposed as well and is
      considered in light of the results of recent animal experimental studies.

PMID- 15148164
TI  - Is computed tomography-negative intracerebral hemorrhage really negative?

PMID- 15148163
TI  - Genotype-phenotype correlation in early-onset Alzheimer disease with presenilin 1
      gene mutations.

PMID- 15148165
TI  - Anticoagulation and thrombolysis for acute ischemic stroke and the role of
      diagnostic magnetic resonance imaging.

PMID- 15148166
TI  - Year 2000 prevalence of Alzheimer disease in the United States.

PMID- 15148167
TI  - Proceedings of the 9th Symposium on Cochlear Implants in Children. April 2003,
      Washington, DC, USA.

PMID- 15148168
TI  - An animal model for cochlear implants.
AB  - OBJECTIVE: To test the feasibility of using the deaf white cat model of early
      onset deafness. We studied the neuronal effects of prosthetic intervention with a
      clinical, "off-the-shelf" multichannel cochlear implant. METHODS: We placed
      cochlear implants in 5 deaf white kittens at age 12 and 24 weeks. The devices
      were activated and stimulated in the laboratory using a clinical speech processor
      programmed with a high-resolution continuous interleaved sampling (CIS) strategy
      for 8 to 24 weeks. Stimulus parameters were guided by electrically evoked
      brainstem responses and intracochlear-evoked potentials. Kittens were assessed
      with respect to their tolerance and general behavior in response to speech,
      music, and environmental sounds. RESULTS: Surgical complications were minimal,
      and kittens tolerated the experimental procedures well. Subjects were able to
      detect and respond to a specific sound played from a computer speaker.
      Electrophysiologic responses were reliably attainable and showed consistency with
      observed behavioral responses to sound. This experimental paradigm, using
      clinical devices, can be used in a practical research setting in cats.
      CONCLUSIONS: Deafness and other variations in neural activity result in many
      distinct changes to the central auditory pathways. Animal models will facilitate
      assessment of the reversibility of deafness-associated changes at the level of
      the neuron and its connections. Our observations of the feasibility of using
      clinical devices in animal models will enable us to simulate clinical conditions
      in addressing questions about the effects of "replacement" activity on the
      structure and function within the central auditory pathways in deafness.

PMID- 15148169
TI  - Central auditory maturation and babbling development in infants with cochlear
      implants.
AB  - OBJECTIVE: To examine the relationship between the maturation of central auditory
      pathways and the development of canonical (speechlike) babbling in infants with
      cochlear implants. DESIGN: Comparison of the latencies of the P1 cortical
      auditory evoked potential and vocalizations produced by subjects before they were
      fitted with a cochlear implant and at several time points within the first year
      after implantation. SUBJECTS: Two congenitally deaf children who were implanted
      with a multichannel cochlear implant at ages 13 and 14 months. INTERVENTIONS: P1
      response latencies were recorded in response to a /ba/ stimulus before
      implantation and at several time points following implantation. Vocalizations
      produced by the subjects while interacting with their caregiver were
      audiorecorded twice before implantation and at monthly sessions following
      implantation. RESULTS: Subjects showed a rapid decrease in P1 latencies resulting
      in normal P1 latencies within about 3 months after implantation. Before
      implantation, the vocalizations were primarily of a precanonical nature. After 3
      months' experience with the implants, the proportion of canonical vocalizations
      increased dramatically relative to the number of precanonical utterances.
      CONCLUSIONS: Results of this study suggest that the development of P1 response
      latencies and the development of early communicative behaviors may follow a
      similar developmental trajectory in children implanted early. Although
      preliminary, these findings indicate that the development of early communicative
      behaviors following implantation may be positively influenced by the rate of
      plastic changes in central auditory pathways.

PMID- 15148170
TI  - Surface microstructure of the perilymphatic space: implications for cochlear
      implants and cell- or drug-based therapies.
AB  - OBJECTIVE: To study the surface microstructure of the scala tympani and scala
      vestibuli in humans and cats using scanning electron microscopy. DESIGN: Cochleas
      from 8 humans and 4 cats were harvested and the otic capsule and soft tissue
      removed before the cochleas were prepared for scanning electron microscopy.
      Micrographs were taken of the bony surface of both the scala tympani and scala
      vestibuli in each cochlear turn. The diameter and density of the micropores
      (canaliculi perforantes) and the thickness of the osseous spiral lamina (OSL)
      adjacent to Rosenthal's canal was measured. RESULTS: The human cochlea exhibits
      numerous canaliculi on the surface of the scala tympani, particularly associated
      with the OSL. There was a large range of diameters in the modiolar region of the
      OSL (0.2-23.0 micro m). The OSL was also very thin, with a mean thickness of 26.8
      micro m in the base, tapering to 8.4 micro m in the apical turn. Far fewer
      canaliculi were evident in the scala vestibuli. Examination of the cat cochleas
      showed a similar distribution of canaliculi to that seen in the human; however,
      they were smaller in diameter and the OSL was thicker than in the human cochleas.
      CONCLUSIONS: The OSL is a thin and highly porous bony lamina that would appear to
      provide an open and extensive fluid communication channel between the scala
      tympani and Rosenthal's canal. These findings have important implications for the
      design and application of perimodiolar cochlear implant electrode arrays and may
      provide a potential route for drug- and cell-based cochlear therapies delivered
      via the scala tympani.

PMID- 15148171
TI  - Speech-language and educational consequences of unilateral hearing loss in
      children.
AB  - BACKGROUND: In the past, unilateral hearing loss (UHL) in children was thought to
      have little consequence because speech and language presumably developed
      appropriately with one normal-hearing ear. Some studies from the 1980s and 1990s
      have suggested that a significantly increased proportion of children with UHL may
      have educational and/or behavioral problems, compared with their normal-hearing
      peers. Limited data exist about the effect of UHL on acquisition of speech and
      language skills. OBJECTIVE: To review the current literature about the impact UHL
      has on the development of speech and language and educational achievement. DATA
      SOURCE: MEDLINE search between 1966 and June 1, 2003, using the medical subject
      heading "hearing loss," combined with the textword "unilateral." STUDY SELECTION:
      Studies were limited to those written in English, reporting speech-language
      and/or educational results in children. DATA EXTRACTION: Articles were read with
      attention to study design, population, recruitment of subjects, and outcomes
      measured. DATA SYNTHESIS: Problems in school included a 22% to 35% rate of
      repeating at least one grade, and 12% to 41% receiving additional educational
      assistance. Speech and language delays have been reported in some but not all
      studies. CONCLUSIONS: School-age children with UHL appear to have increased rates
      of grade failures, need for additional educational assistance, and perceived
      behavioral issues in the classroom. Speech and language delays may occur in some
      children with UHL, but it is unclear if children "catch up" as they grow older.
      Research into this area is necessary to clarify these issues and to determine
      whether interventions may prevent potential problems.

PMID- 15148172
TI  - Auditory steady-state responses for children with severe to profound hearing
      loss.
AB  - OBJECTIVE: To investigate the clinical usefulness of the dichotic single
      frequency auditory steady-state response (ASSR) for estimation of behavioral
      thresholds in children with severe to profound congenital sensorineural hearing
      loss. DESIGN: A comparative experimental research design was selected to compare
      behavioral and ASSR thresholds for the sample. Behavioral pure-tone audiometry
      served as the criterion standard. SETTING: Hearing Clinic, Department of
      Communication Pathology, University of Pretoria, Pretoria, South Africa.
      PATIENTS: A referred sample of 10 patients (20 ears), 5 girls and 5 boys aged 10
      to 15 years (mean age, 13 years 4 months), with severe to profound sensorineural
      hearing impairment. MAIN OUTCOME MEASURES: The difference, and correlation,
      between 160 pure-tone behavioral and ASSR thresholds at 0.5, 1, 2, and 4 kHz.
      RESULTS: Mean differences between ASSR and behavioral thresholds were 6 dB for
      0.5 kHz and 4 dB for 1, 2, and 4 kHz, with standard deviations varying between 8
      and 12 dB. No significant differences (P<.05) were observed between ASSR and
      behavioral thresholds, except at 0.5 kHz, and Pearson correlation coefficients
      varied between 0.58 and 0.74 across the evaluated frequencies, with best
      correlation at 1 kHz and worst at 0.5 kHz. CONCLUSIONS: The ASSR thresholds
      provided reliable estimations of behavioral thresholds for children with severe
      to profound hearing loss and indicated an increased sensitivity for more profound
      hearing loss.

PMID- 15148173
TI  - Auditory sensitivity in children using the auditory steady-state response.
AB  - OBJECTIVE: To determine the effectiveness of auditory steady-state response
      (ASSR) as a measure of hearing sensitivity in young children suspect for
      significant hearing loss. DESIGN: Within-subject comparisons of click auditory
      brainstem response (ABR) thresholds and ASSR thresholds. SUBJECTS: The study
      population comprised 42 children suspect for hearing loss and subsequently
      referred for hearing assessment using electrophysiologic techniques. MAIN OUTCOME
      MEASURES: Electrophysiologic threshold responses for click ABR and ASSR stimuli
      (0.5, 1, 2, and 4 kHz) for right and left ears. RESULTS: Based on ABR and ASSR
      thresholds, 50% of the subjects demonstrated significant hearing loss in the
      severe to profound range. In some subjects, ASSRs were present at higher stimulus
      levels when click ABRs were absent. Significant correlations (P<.05) were found
      between high-frequency ASSR and click ABR thresholds for this study sample. For
      some subjects, ASSR findings suggested differences between ears that were not
      observable from the no-response click ABR results. CONCLUSIONS: Auditory steady
      state response testing may provide additional information for children who
      demonstrate hearing levels in the severe to profound range. This information may
      be helpful when selecting the ear for cochlear implantation for a young hearing
      impaired child. Multiple objective methods, such as ABR and ASSR testing, may be
      needed to determine accurate hearing sensitivity for young children being
      considered for sensory devices, and in particular, cochlear implants.

PMID- 15148174
TI  - GJB2 gene mutations in cochlear implant recipients: prevalence and impact on
      outcome.
AB  - OBJECTIVE: To determine the prevalence of GJB2 gene mutations in patients
      undergoing cochlear implantation (CI) and their impact on rehabilitative outcome
      following implantation. DESIGN: Prospective determination of GJB2 mutation by
      sequence analysis by denaturing high-performance liquid chromatography and its
      correlation with outcome following CI. SETTINGS: Two tertiary academic medical
      centers. PATIENTS: Subjects who have met the audiologic criteria and have
      undergone CI. RESULTS: Of 77 cochlear implant recipients screened, 13 (18%)
      harbored a detectable sequence alteration in the GJB2 gene. Only 3 of these 13
      patients had hearing loss clearly attributable to a biallelic GJB2 mutation.
      There were 2 patients with homozygous mutations, including a 35delG and a 167delT
      mutation, and a third with a compound heterozygous mutation. Of the remaining 10
      patients, 8 had 1 deafness allele, while 2 had a normal polymorphism that was not
      believed to be implicated in the hearing loss. Six patients had the common 35delG
      mutation: 5 patients had heterozygous mutations, which are probably not related
      to the underlying hearing loss (a second deafness allele cannot be ruled out in
      these cases because of the screening methodology used), while 1 patient had a
      homozygous mutation, which was clearly implicated in the patient's deafness.
      Rehabilitative outcome among those with detectable sequence alterations, as well
      as the 3 patients with biallelic mutations, varied but were similar on average
      when compared with outcomes seen in our entire CI population. CONCLUSIONS: A
      large percentage of implant candidates harbor mutations or sequence alterations
      in the GJB2 gene, although only a small number of these changes are biallelic and
      a clear cause of the hearing loss. These results demonstrate that patients with
      GJB2-related deafness clearly benefit from CI.

PMID- 15148175
TI  - The impact of cochlear implants on young deaf children: new methods to assess
      cognitive and behavioral development.
AB  - Much evidence suggests that, early in life, auditory input and communication are
      essential for the normal development of language, cognition, and behavior. Thus,
      deaf children, who experience significant disruptions in auditory input, are
      likely to show delays not only in the production of oral language but in other
      important aspects of development such as visual attention and behavioral control.
      Cochlear implants have shown tremendous promise in restoring auditory information
      to deaf children and concomitant improvements in speech recognition and
      production. However, little is known about how cochlear implants affect
      psychological variables. In this multisite trial, we assess the effects of
      cochlear implants on a range of developmental outcomes, including visual
      attention, problem-solving skills, symbolic play, and social adjustment.
      Measuring these constructs in young children, primarily younger than 2 years, has
      presented a number of unique challenges. In this article, we describe the methods
      used to assess these variables in young children and present preliminary findings
      comparing joint attention and symbolic play skills in a small sample of age
      matched deaf and hearing children. As expected, deaf children performed more
      poorly than hearing children on measures of attention and symbolic play. As
      auditory input is restored via a cochlear implant, we predict that significant
      improvements in these variables will be observed.

PMID- 15148176
TI  - The importance of high-frequency audibility in the speech and language
      development of children with hearing loss.
AB  - OBJECTIVES: To review recent research studies concerning the importance of high
      frequency amplification for speech perception in adults and children with hearing
      loss and to provide preliminary data on the phonological development of normal
      hearing and hearing-impaired infants. DESIGN AND SETTING: With the exception of
      preliminary data from a longitudinal study of phonological development, all of
      the reviewed studies were taken from the archival literature. To determine the
      course of phonological development in the first 4 years of life, the following 3
      groups of children were recruited: 20 normal-hearing children, 12 hearing
      impaired children identified and aided up to 12 months of age (early-ID group),
      and 4 hearing-impaired children identified after 12 months of age (late-ID
      group). Children were videotaped in 30-minute sessions at 6- to 8-week intervals
      from 4 to 36 months of age (or shortly after identification of hearing loss) and
      at 2- and 6-month intervals thereafter. Broad transcription of child
      vocalizations, babble, and words was conducted using the International Phonetic
      Alphabet. A phoneme was judged acquired if it was produced 3 times in a 30-minute
      session. SUBJECTS: Preliminary data are presented from the 20 normal-hearing
      children, 3 children from the early-ID group, and 2 children from the late-ID
      group. RESULTS: Compared with the normal-hearing group, the 3 children from the
      early-ID group showed marked delays in the acquisition of all phonemes. The delay
      was shortest for vowels and longest for fricatives. Delays for the 2 children
      from the late-ID group were substantially longer. CONCLUSIONS: The reviewed
      studies and preliminary results from our longitudinal study suggest that (1)
      hearing-aid studies with adult subjects should not be used to predict speech and
      language performance in infants and young children; (2) the bandwidth of current
      behind-the-ear hearing aids is inadequate to accurately represent the high
      frequency sounds of speech, particularly for female speakers; and (3) preliminary
      data on phonological development in infants with hearing loss suggest that the
      greatest delays occur for fricatives, consistent with predictions based on
      hearing-aid bandwidth.

PMID- 15148177
TI  - Communication abilities of children with aided residual hearing: comparison with
      cochlear implant users.
AB  - OBJECTIVE: To compare the communication outcomes between children with aided
      residual hearing and children with cochlear implants. DESIGN: Measures of speech
      recognition and language were administered to pediatric hearing aid users and
      cochlear implant users followed up longitudinally as part of an ongoing
      investigation on cochlear implant outcomes. The speech recognition measures
      included the Lexical Neighborhood Test, Phonetically Balanced-Kindergarten Word
      Lists, and the Hearing in Noise Test for Children presented in quiet and noise
      (+5 dB signal-to-noise ratio). Language measures included the Peabody Picture
      Vocabulary Test: Third Edition (PPVT-III), the Reynell Developmental Language
      Scales, and the Clinical Evaluation of Language Fundamentals-Revised. Subjects
      The experimental group was composed of 39 pediatric hearing aid users with a mean
      unaided pure-tone average threshold of 78.2 dB HL (hearing level). The comparison
      group was composed of 117 pediatric cochlear implant users with a mean unaided
      pure-tone average threshold of 110.2 dB HL. On average, both groups lost their
      hearing at younger than 1 year and were fitted with their respective sensory aids
      at 2 to 2.6 years of age. Not every child was administered every test for a
      variety of reasons. RESULTS: Between-group performance was equivalent on most
      speech recognition and language measures. The primary difference found between
      groups was on the PPVT-III, in which the hearing aid group had a significantly
      higher receptive vocabulary language quotient than the cochlear implant group.
      Notably, the cochlear implant group was substantially younger than the hearing
      aid group and had less experience with their sensory devices on this measure.
      CONCLUSION: Data obtained from children with aided residual hearing can be useful
      in determining cochlear implant candidacy.

PMID- 15148178
TI  - Effect of age at cochlear implantation on auditory skill development in infants
      and toddlers.
AB  - OBJECTIVES: To investigate the effect of age at cochlear implantation on the
      auditory development of children younger than 3 years and to compare these
      children's auditory development with that of peers with normal hearing. DESIGN:
      Using a repeated-measures paradigm, auditory skill development was evaluated
      before and 3, 6, and 12 months after implantation. Data were compared with
      previously published data from cohorts with normal hearing. PARTICIPANTS: One
      hundred seven hearing-impaired children (age range, 12-36 months) who received a
      cochlear implant during clinical trials in North America. MAIN OUTCOME MEASURE:
      Auditory skill development was assessed using the Infant-Toddler Meaningful
      Auditory Integration Scale, a tool that provides a quantitative measure in
      children as young as newborns. RESULTS: Infants and toddlers who receive implants
      show rapid improvement in auditory skills during the first year of device use
      regardless of age at implantation, although younger children achieve higher
      scores. Children who undergo implantation at a younger age acquire auditory
      skills nearer to those of their peers with normal hearing at a younger age. The
      mean rate of acquisition of auditory skills is similar to that of infants and
      toddlers with normal hearing regardless of age at implantation. CONCLUSION:
      Performing implantation in children with profound hearing loss at the youngest
      age possible allows the best opportunity for them to acquire communication skills
      that approximate those of their peers with normal hearing.

PMID- 15148179
TI  - Outcomes for cochlear implant users with significant residual hearing:
      implications for selection criteria in children.
AB  - OBJECTIVES: To develop an evidence-based technique for providing recommendations
      to candidates for cochlear implantation with significant residual hearing and to
      assess the efficacy of the approach. DESIGN: Modified selection criteria were
      derived from an analysis of the postoperative performance for a large group of
      adult cochlear implant users. In particular, the distributions of results for
      implant users with significant preoperative open-set speech perception were
      reviewed. This suggested that the candidates had a good chance (>75%) of overall
      improvement if they obtained open-set sentence scores in quiet of up to 70% in
      the best-aided condition and scores of up to 40% in the ear to undergo
      implantation. PATIENTS: A group of 45 adult implantation candidates who fit the
      modified criteria and who underwent preimplantation and postimplantation
      assessment to compare actual results with those predicted from the distributions.
      RESULTS: The speech perception results showed that 36 subjects (80%) had improved
      open-set sentence scores with the cochlear implant compared with their best-aided
      preoperative performance (mean improvement, 20.5%). Forty-four (98%) had improved
      open-set sentence scores for the ear undergoing implantation (mean improvement,
      65.3%). CONCLUSIONS: The general concept of using the distribution of speech
      perception results to make evidence-based recommendations for candidates for
      cochlear implants is supported by this study. The approach can be used across
      different subpopulations, including older children with significant residual
      auditory skills, and for different outcome measures. It is important that the
      data used to provide recommendations and modify selection criteria are from an
      unselected sample of implant users of adequate size. This study highlights the
      continuing need to evaluate speech perception performance carefully before and
      after cochlear implantation.

PMID- 15148180
TI  - Bimodal speech perception in infant hearing aid and cochlear implant users.
AB  - OBJECTIVES: To determine the feasibility of replicating prior bimodal perception
      findings with hearing-impaired infants during their preimplant, hearing aid
      trial, and postimplant experiences; secondarily, to determine the point in
      development at which these infants were able to match phonetic information in the
      lips and voice for the vowels /a/ and /i/. METHODS: A total of 10 infants with
      hearing loss, aged 4 to 24 months, were assessed at least once prior to cochlear
      implantation and previous to implant stimulation. The Split-Screen Preferential
      Looking Procedure was used to evaluate the bimodal perception skills of these
      infants. RESULTS: Examples of individual bimodal perception data and preliminary
      group data are presented. A difference in performance across preimplant and
      postimplant test sessions was noted for the individuals and the group.
      CONCLUSION: These data provide evidence that the infants' audibility levels were
      improved by their cochlear implants, which may have contributed to their evolving
      ability to match phonetic information in the lips and voice.

PMID- 15148181
TI  - Nonword imitation by children with cochlear implants: consonant analyses.
AB  - OBJECTIVES: To complete detailed linguistic analyses of archived recordings of
      pediatric cochlear implant users' imitations of nonwords; to gain insight into
      the children's developing phonological systems and the wide range of variability
      in nonword responses. DESIGN: Nonword repetition: repetition of 20 auditory-only
      English-sounding nonwords. SETTING: Central Institute for the Deaf "Education of
      the Deaf Child" research program, St Louis, Mo. PARTICIPANTS: Eighty-eight 8- to
      10-year-old experienced pediatric cochlear implant users. MAIN OUTCOME MEASURES:
      Several different consonant accuracy scores based on the linguistic structure
      (voicing, place, and manner of articulation) of the consonants being imitated;
      analysis of the errors produced for all consonants imitated incorrectly. RESULTS:
      Seventy-six children provided a response to at least 75% of the nonword stimuli.
      In these children's responses, 33% of the target consonants were imitated
      correctly, 25% of the target consonants were deleted, and substitutions were
      provided for 42% of the target consonants. The children tended to correctly
      reproduce target consonants with coronal place (which involve a mid-vocal tract
      constriction) more often than other consonants. Poorer performers tended to
      produce more deletions than the better performers, but their production errors
      tended to follow the same patterns as the better performers. CONCLUSIONS: Poorer
      performance on labial consonants suggests that scores were affected by the lack
      of visual cues such as lip closure. Oral communication users tended to perform
      better than total communication users, indicating that oral communication methods
      are beneficial to the development of pediatric cochlear implant users'
      phonological processing skills.

PMID- 15148182
TI  - Consonant production and language skills in Mandarin-speaking children with
      cochlear implants.
AB  - OBJECTIVES: To investigate the phonemic inventories of syllable-initial
      consonants in Mandarin-speaking children with cochlear implants, assessing the
      relationship between the children's mastery levels of consonant production and
      their receptive and expressive language skills. DESIGN: Descriptive study.
      SETTING: Chi-Mei Medical Center, Tainan, Taiwan. PATIENTS: The 30 prelingually
      deaf children with cochlear implants who participated in the study ranged in age
      from 6 years to 12 years 6 months, and their age at implantation ranged from 2
      years 3 months to 10 years 3 months. The average length of device experience was
      3 years 7 months (range, 1 year 7 months to 6 years 5 months). None of the
      children was identified with concomitant learning disabilities. OUTCOME MEASURES:
      The 21 Mandarin syllable-initial consonants were elicited using a set of 105
      pictures. Two language assessment tools were used to evaluate the children's
      receptive vocabulary skills as well as their overall receptive and expressive
      language development. RESULTS: The mean +/- SD score for correct consonant
      production was 57.9% +/- 19.5%. Regarding the manner of articulation, plosives
      received the highest average correct percentage whereas nasals, affricates,
      fricatives, and the lateral approximant /l/ were less frequently correct. The
      children's overall percentage of correct scores for consonant production and
      receptive vocabulary measure were significantly correlated (r = 0.51; P =.005).
      Additionally, correlation coefficients were significant between the overall score
      for correct consonant production and both the scores for receptive language
      measure (r = 0.65; P<.001) and expressive language measure (r = 0.76; P<.001).
      The participants' consonant production skills were negatively correlated with age
      at implantation (r = - 0.46; P =.01) and positively correlated with length of
      experience with cochlear implant (r = 0.45; P =.02). CONCLUSIONS: Mastery levels
      of Mandarin syllable-initial consonants remained moderately low in prelingually
      deaf children with cochlear implants. The present results suggest a significant
      association between consonant production skills and language development in these
      children.

PMID- 15148183
TI  - Effects of temporal and spectral alterations of speech feedback on speech
      production by persons with hearing loss.
AB  - OBJECTIVE: To evaluate the effects of delay and spectral alteration of speech
      feedback (SF) on the speaking rate and voice pitch in adult users of hearing aids
      (HAs) and cochlear implants (CIs). METHODS: Repeated-measure, completely crossed,
      2-factor design. Spectral alterations were implemented by replacing SF with noise
      that was filtered into 1-, 2-, or 4-frequency bands and speech-modulated in real
      time. Delays varied from 25 to 200 milliseconds. SUBJECTS: Seven HA users with
      severe to profound hearing loss and 6 CI users were randomly recruited by public
      advertising. All were postlingually deafened adults with intelligible speech.
      RESULTS: The average speaking rate significantly decreased and rate variability
      significantly increased with increase in SF delay for both groups. Spectral
      alterations of SF reduced the effect on speaking rate in the HA group but not in
      the CI group. Spectral alterations did not significantly affect rate variability
      in the HA group but did so in the CI group. Average voice pitch increased
      significantly with increase in SF delay and with spectral alterations of SF in
      the HA group. No significant effects on average pitch of CI users were noted.
      CONCLUSIONS: The 2 groups were affected differently by the delay and spectral
      alterations of SF. The differences possibly reflect greater spectral resolution
      ability in the case of CI users and greater audibility of bone-conducted SF
      (particularly in the low-frequency region) among the HA users.

PMID- 15148184
TI  - Effects of central nervous system residua on cochlear implant results in children
      deafened by meningitis.
AB  - BACKGROUND: This study explored factors associated with speech recognition
      outcomes in postmeningitic deafness (PMD). The results of cochlear implantation
      may vary in children with PMD because of sequelae that extend beyond the auditory
      periphery. OBJECTIVE: To determine which factors might be most determinative of
      outcome of cochlear implantation in children with PMD. DESIGN: Retrospective
      chart review. SETTING: A referral center for pediatric cochlear implantation and
      rehabilitation. SUBJECTS: Thirty children with cochlear implants who were
      deafened by meningitis were matched with subjects who were deafened by other
      causes based on the age at diagnosis, age at cochlear implantation, age at which
      hearing aids were first used, and method of communication used at home or in the
      classroom. MAIN OUTCOME MEASURE: Speech perception performance within the first 2
      years after cochlear implantation and its relationship with presurgical cognitive
      measures and medical history. RESULTS: There was no difference in the overall
      cognitive or postoperative speech perception performance between the children
      with PMD and those deafened by other causes. The presence of postmeningitic
      hydrocephalus, however, posed greater challenges to the rehabilitation process,
      as indicated by significantly smaller gains in speech perception and a
      predilection for behavioral problems. By comparison, cochlear scarring and
      incomplete electrode insertion had no impact on speech perception results.
      CONCLUSIONS: Although the results demonstrated no significant delay in cognitive
      or speech perception performance in the PMD group, central nervous system
      residua, when present, can impede the acquisition of speech perception with a
      cochlear implant. Central effects associated with PMD may thus impact language
      learning potential; cognitive and behavioral therapy should be considered in
      rehabilitative planning and in establishing expectations of outcome.

PMID- 15148185
TI  - Cochlear implants for children with significant residual hearing.
AB  - BACKGROUND: Previous research suggests that children with pure-tone averages of
      greater than 90 dB hearing level and/or open-set sentence perception of less than
      30% may derive significant benefit from cochlear implantation. OBJECTIVE: To
      evaluate postoperative speech perception benefit and bilateral-bimodal benefit
      for 16 children whose preimplant speech perception scores exceeded conservative
      candidacy guidelines. STUDY DESIGN: Preimplant and postimplant repeated-measure
      design. METHODS: Sixteen child subjects who obtained 30% or greater on preimplant
      open-set sentence material, presented live voice audition alone, were selected
      for this study. Preimplant pure-tone averages ranged from 73 to 110 dB in the
      better aided ear. Preimplant and postimplant open-set word and sentence testing
      was completed in quiet and with competing background noise for separate ear and
      binaural conditions. RESULTS: Fourteen of 16 subjects had improved speech
      perception scores across all test materials after implantation. Group means were
      significantly higher for all test materials. Results in the bimodal-bilateral
      condition were significantly higher than implant alone for open-set word tests
      (scored for phonemes) and open-set sentences in quiet. CONCLUSION: The results of
      this study suggest that, with appropriate counseling and management, some
      children with significant residual hearing benefit from cochlear implantation, in
      particular improved speech understanding due to bimodal-bilateral hearing.

PMID- 15148186
TI  - Prelinguistic communication and subsequent language acquisition in children with
      cochlear implants.
AB  - OBJECTIVE: To investigate the relationship between prelinguistic communication
      behaviors and subsequent language development after cochlear implantation in deaf
      children. Evaluative tools with predictive validity for language potential in
      very young deaf children remain elusive. SETTING: A tertiary care cochlear
      implant center and a preschool setting of spoken language immersion in which oral
      language development is emphasized through auditory and oral motor subskill
      practice. SUBJECTS: Eighteen prelingually deaf children who underwent unilateral
      implantation at an average age of 15 months also underwent testing with the
      Communication and Symbolic Behavior Scales (CSBS) before device activation and
      with the Reynell Developmental Language Scales (RDLS) at an average of 20 months
      after cochlear implantation. METHODS: A prospective study correlated preoperative
      communication behavior assessments of 18 children who were candidates for
      cochlear implantation. We examined the value of prelinguistic behavioral testing
      with the CSBS in predicting later language level after cochlear implantation as
      reflected in RDLS scores. RESULTS: We found positive, though weak, correlations
      between prelinguistic communication skills (CSBS scores) and language learning
      after cochlear implantation (RDLS scores). Linear correlation between test
      results failed to reach statistical significance (receptive comparisons, P =.17;
      expressive comparisons, P =.13). CONCLUSIONS: Evaluating the quality of
      prelinguistic communication behaviors potentially adds important predictive
      information to profiles of children who are candidates for cochlear implantation.
      Correlative analysis suggests that early CSBS testing may provide useful clinical
      information. Poor CSBS scores may serve as a precaution: if children lack an
      appropriate prelinguistic behavioral repertoire, the emergence of age-appropriate
      formal language may be at risk. Observations suggest that symbolic prelinguistic
      behaviors are necessary, but not sufficient, for the development of strong
      linguistic skills. The variability of behavioral measures in very young deaf
      children poses challenges in designing objective measures with predictive value
      for later language level.

PMID- 15148187
TI  - Performance of subjects fit with the Advanced Bionics CII and Nucleus 3G cochlear
      implant devices.
AB  - OBJECTIVE: To determine if subjects who used different cochlear implant devices
      and who were matched on consonant-vowel-consonant (CNC) identification in quiet
      would show differences in performance on speech-based tests of spectral and
      temporal resolution, speech understanding in noise, or speech understanding at
      low sound levels. DESIGN: The performance of 15 subjects fit with the CII Bionic
      Ear System (CII Bionic Ear behind-the-ear speech processor with the Hi-Resolution
      sound processing strategy; Advanced Bionics Corporation) was compared with the
      performance of 15 subjects fit with the Nucleus 24 electrode array and ESPrit 3G
      behind-the-ear speech processor with the advanced combination encoder speech
      coding strategy (cochlear corporation). SUBJECTS: Thirty adults with late-onset
      deafness and above-average speech perception abilities who used cochlear
      implants. MAIN OUTCOME MEASURES: Vowel recognition, consonant recognition,
      sentences in quiet (74, 64, and 54 dB SPL [sound pressure level]) and in noise
      (+10 and +5 dB SNR [signal-to-noise ratio]), voice discrimination, and melody
      recognition. RESULTS: Group differences in performance were significant in 4
      conditions: vowel identification, difficult sentence material at +5 dB and +10 dB
      SNR, and a measure that quantified performance in noise and low input levels
      relative to performance in quiet. CONCLUSIONS: We have identified tasks on which
      there are between-group differences in performance for subjects matched on CNC
      word scores in quiet. We suspect that the differences in performance are due to
      differences in signal processing. Our next goal is to uncover the signal
      processing attributes of the speech processors that are responsible for the
      differences in performance.

PMID- 15148188
TI  - Development of spoken language grammar following cochlear implantation in
      prelingually deaf children.
AB  - OBJECTIVES: To assess the development of grammar comprehension in spoken language
      in prelingually deaf children following cochlear implantation and compare their
      grammatical abilities with those of their hearing peers. DESIGN: A prospective
      study of 82 consecutive prelingually deaf children up to 5 years following
      implantation. The children were less than 7 years old at the time of implantation
      (mean age +/- SD, 4.2 +/- 1.3 years). All received the same multichannel cochlear
      implant system. No child was lost to follow-up and there were no exclusions from
      the study. SETTING: Tertiary referral cochlear implant center. METHODS: The
      children were assessed using the Test for Reception of Grammar. This individually
      administered, multiple-choice test designed to assess the understanding of
      grammatical contrasts in the English language also allows direct comparison of
      grammar comprehension between test subjects and their normal-hearing peers.
      RESULTS: Before implantation, only a small proportion (2%) of prelingually deaf
      children were above the first percentile of their normal-hearing peers. This
      percentage increased to 40% and 67%, respectively, 3 and 5 years after
      implantation; and 5 years after implantation, 20% of the children performed
      between the 25th and the 75th percentile or better. In the subgroup of children
      who received their cochlear device before the age of 4 years, this percentage
      reached 36%. CONCLUSIONS: Spoken language grammar acquisition in prelingually
      deaf children with a cochlear implant was found to be considerably delayed.
      However, there was a clear trend toward the development of grammar skills
      following cochlear implantation, and the greatest advance was made by children
      who received their implant at a younger age. These findings support the present
      trend toward early implantation.

PMID- 15148190
TI  - Mode of communication and classroom placement impact on speech intelligibility.
AB  - OBJECTIVE: To examine the impact of classroom placement and mode of communication
      on speech intelligibility scores in children aged 8 to 9 years using multichannel
      cochlear implants. DESIGN: Classroom placement (special education, partial
      mainstream, and full mainstream) and mode of communication (total communication
      and auditory-oral) reported via parental rating scales before and 4 times after
      implantation were the independent variables. Speech intelligibility scores
      obtained at 8 to 9 years of age were the dependent variables. PARTICIPANTS: The
      study included 131 congenitally deafened children between the ages of 8 and 9
      years who received a multichannel cochlear implant before the age of 5 years.
      RESULTS: Higher speech intelligibility scores at 8 to 9 years of age were
      significantly associated with enrollment in auditory-oral programs rather than
      enrollment in total communication programs, regardless of when the mode of
      communication was used (before or after implantation). Speech intelligibility at
      8 to 9 years of age was not significantly influenced by classroom placement
      before implantation, regardless of mode of communication. After implantation,
      however, there were significant associations between classroom placement and
      speech intelligibility scores at 8 to 9 years of age. Higher speech
      intelligibility scores at 8 to 9 years of age were associated with classroom
      exposure to normal-hearing peers in full or partial mainstream placements than in
      self-contained, special education placements. CONCLUSIONS: Higher speech
      intelligibility scores in 8- to 9-year-old congenitally deafened cochlear implant
      recipients were associated with educational settings that emphasize oral
      communication development. Educational environments that incorporate exposure to
      normal-hearing peers were also associated with higher speech intelligibility
      scores at 8 to 9 years of age.

PMID- 15148189
TI  - Speech, language, and reading skills after early cochlear implantation.
AB  - OBJECTIVE: To examine whether age at cochlear implantation or duration of implant
      use is associated with speech, language, and reading skills exhibited at age 8 to
      9 years in children who underwent implantation by age 5 years. DESIGN:
      Performance outcomes in speech perception, speech production, language, and
      reading were examined in terms of the age at which children first received a
      cochlear implant (2, 3, or 4 years), the age they received an updated (Spectra)
      processor, and the duration of use of an implant and an updated processor.
      SETTING: Data collection was conducted at summer research camps held over 4
      consecutive years to maximize the number of children available at a specific age
      (8-9 years). Children were tested individually by experienced examiners, and
      their parents and therapists provided background and educational history
      information. PARTICIPANTS: A total of 181 children from 33 different states and 5
      Canadian provinces who received a cochlear implant by age 5 years were tested. A
      subsample of 133 children with performance IQ scores of 80 or greater and onset
      of deafness at birth were selected for the age-at-implantation analysis. Another
      subsample of 39 children with deafness acquired by age 3 years was also examined.
      OUTCOME MEASURES: A battery of tests of speech perception, speech production,
      language, and reading was administered to each child and reduced to a single
      factor score for each skill. RESULTS: Correlation coefficients between age at
      implantation and duration of use did not reach significance for any of the
      outcome skills measured. Age at which the updated speech processor (Spectra) was
      fitted was significantly related to speech production outcome (earlier use of an
      updated processor was associated with greater speech intelligibility) but not to
      any other skill area. However, more of the children who underwent implantation at
      age 2 years (43%) achieved combined speech and language skills commensurate with
      their age-matched peers with normal hearing than did children who underwent
      implantation at age 4 years (16%). Furthermore, normal speech and language skills
      were documented in 80% of children who lost hearing after birth and who underwent
      implantation within a year of onset of deafness. CONCLUSIONS: For children who
      receive a cochlear implant between the ages of 2 and 4 years, early cochlear
      implantation does not ensure better speech perception, speech production,
      language, or reading skills. However, greater speech and language proficiency may
      be expected from children who exhibit normal hearing for even a brief period
      after birth and receive a cochlear implant shortly after losing their hearing.
      Further research examining the benefits of cochlear implantation before age 2
      years will help families and clinicians better understand the time-sensitive
      nature of the decision to conduct cochlear implant surgery.

PMID- 15148191
TI  - Bilingual oral language proficiency in children with cochlear implants.
AB  - OBJECTIVE: To document oral language proficiency in a group of prelingually deaf
      bilingual children with a cochlear implant. DESIGN: Using a repeated-measures
      paradigm, oral language skills in the first and second language were evaluated at
      2 yearly intervals after implantation. Language data were compared with normative
      data from children with normal hearing. SUBJECTS: Twelve deaf children between
      the ages of 20 months and 15 years who had received a cochlear implant before the
      age of 3 years. OUTCOME MEASURE: First-language skills were assessed using 1 of 2
      standardized tests, either the Oral and Written Language Scales or the Reynell
      Developmental Language Scales, depending on the child's age. Second-language
      proficiency was assessed using the Student Oral Language Observation Matrix.
      RESULTS: Average standard scores in the first language fell solidly within the
      average range of normal-hearing peers. Second-language skills showed steady
      improvement from year 1 to year 2, along a continuum that reflected the amount
      and intensity of exposure of the child to the second language and the length of
      experience with the implant. CONCLUSION: A cochlear implant can make oral
      proficiency in more than 1 language possible for prelingually deaf children.

PMID- 15148192
TI  - Bilateral cochlear implants in adults and children.
AB  - OBJECTIVE: To measure the benefit (ie, sound localization and speech
      intelligibility in noise) of bilateral cochlear implants (CIs) in adults and in
      children. DESIGN, SETTING, AND PATIENTS: Seventeen adults and 3 children
      underwent testing 3 months after activation of bilateral hearing. Adults received
      their devices in a simultaneous procedure and children in sequential procedures
      (3-8 years apart). Adults underwent testing of sound localization and speech
      intelligibility, with a single CI and bilaterally. Children underwent testing of
      sound localization, right/left discrimination, and speech intelligibility, with
      the first CI alone and bilaterally. We used computer games to attract the
      children's attention and engage them in the psychophysical tasks for long periods
      of time. RESULTS: Preliminary findings suggest that, for adults, bilateral
      hearing leads to better performance on the localization task, and on the speech
      task when the noise is near the poorer of the 2 ears. In children, localization
      and discrimination are slightly better under bilateral conditions, but not
      remarkably so. On the speech tasks, 1 child did not benefit from bilateral
      hearing. Two children showed consistent improvement with bilateral hearing when
      the noise was near the side that underwent implantation first. CONCLUSIONS:
      Bilateral CIs may offer advantages to some listeners. The tasks described in this
      study might offer a powerful tool for measuring such advantages, especially in
      young children. The extent of the advantage, however, is difficult to ascertain
      after 3 months of bilateral listening experience, and might require a more
      prolonged period of adjustment and learning. Future work should be aimed at
      examining these issues.

PMID- 15148193
TI  - Auditory brainstem implantation in 12- to 18-year-olds.
AB  - OBJECTIVE: To assess the effects of the side of implantation (first-side vs
      second-side vestibular schwannoma); the presence of nonauditory sensations; the
      general health, expectations, and motivation of the patients; and a support group
      on the use of a multichannel auditory brainstem implant (ABI) in 12- to 18-year
      old patients with neurofibromatosis 2. DESIGN: Since 1992, 21 individuals (age
      range, 12-18 years) who were deafened by neurofibromatosis 2 have undergone
      implantation with a multichannel ABI at the House Ear Institute, Los Angeles,
      Calif. The patients were categorized regarding side of implantation, presence of
      remaining hearing (in first-side implant recipients), incidence of nonauditory
      sensations, and ABI use or nonuse. They were also rated on factors of general
      health, personal motivation, expectations, and family support. RESULTS: Nineteen
      (95%) of 20 teenagers tested received hearing sensations from their ABIs. Eleven
      teenagers used their ABIs regularly, but 8 did not. Of the nonusers, 2 had good
      remaining hearing on the side with the second vestibular schwannoma, 2 had
      persistent nonauditory sensations, and 4 became program dropouts. None of the
      dropouts had remaining hearing, significant nonauditory sensations, or poor
      health; however, they generally rated poorly in terms of personal motivation,
      expectations, and family support. One patient with good family support returned
      with excellent ABI results after 4 years' absence. CONCLUSIONS: The multichannel
      ABI is an effective means of providing hearing sensations to young patients
      deafened by neurofibromatosis 2. Preoperative counseling regarding the importance
      of such factors as expectations, personal motivation, and family support is
      invaluable and can promote successful adaptation to the device. With patience and
      support, even young nonusers (including program dropouts) can become successful
      device users.

PMID- 15148195
TI  - Measuring progress in children with autism spectrum disorder who have cochlear
      implants.
AB  - OBJECTIVE: To quantify progress after cochlear implantation for children with
      autism spectrum disorder (ASD). STUDY DESIGN: Retrospective review of speech and
      language and speech perception test scores of children with autism who have
      received a cochlear implant at our center. SETTING: University of Michigan
      Medical Center, Cochlear Implant Program. PATIENTS: Six children, ages 3 to 16
      years, who received cochlear implants at the our center. All children were
      diagnosed as having ASD by a neuropsychologist, either before or after receiving
      a cochlear implant. MAIN OUTCOME MEASURES: Children participated in preoperative
      and postoperative speech and language and speech perception testing. A survey was
      administered to parents to evaluate subjective impressions of cochlear implant
      benefit and quality of life before and after implantation. RESULTS: Improved
      scores were recorded for children on whom standardized expressive and receptive
      vocabulary testing was possible. Children who could not complete standardized
      tests demonstrated improvement in raw scores. Improvement on the Meaningful
      Auditory Integration Scale was noted for the 4 of 7 children who completed the
      scale preoperatively and postoperatively. Survey results suggested changes in
      responsiveness to sound, interest in music, vocalization, and eye contact
      following implantation. Five of the 6 families indicated that they would
      recommend a cochlear implant to another family in a similar situation.
      CONCLUSIONS: Gains made by children in our study were small compared with the
      general implant population; however, when compared with themselves
      preoperatively, these children did demonstrate progress. Improvements in
      behaviors and interaction point to a quality of life benefit following
      implantation that is difficult to quantify.

PMID- 15148196
TI  - Children with cochlear implants: changing parent and deaf community perspectives.
AB  - OBJECTIVE: To examine changing parent and deaf community perspectives related to
      pediatric cochlear implantation. DESIGN: This research is based primarily on 2
      nonrandom study designs. In the first study, conducted by the Gallaudet
      University Research Institute, Washington, DC, in the spring of 1999, a 12-page
      questionnaire was distributed to 1841 parents of children with cochlear implants;
      439 questionnaires were returned. In the second study, we conducted 56 interviews
      with parents of 62 children with implants (and 1 without). SUBJECTS: Parents of
      children with cochlear implants; Gallaudet University faculty, staff, students,
      and alumni. RESULTS: While parents frequently receive conflicting information
      about educational and communication options for their child, they generally
      support signing before and after implantation. The parents of a child with an
      implant have a great interest in their child's spoken language development, and
      most would like to have had their child receive an implant earlier. Children with
      implants are educated in a variety of educational settings. Mainstreamed children
      with implants often continue to require classroom support services, and children
      with implants are frequently not isolated from both deaf and hearing peers.
      Parents have mixed experiences when getting information from persons in the deaf
      community. COMMENT: Opposition to pediatric cochlear implantation within the deaf
      community is giving way to the perception that it is one of a continuum of
      possibilities for parents to consider. To ensure optimal use of the cochlear
      implant, parents need to remain involved in their child's social and educational
      development.

PMID- 15148194
TI  - Behavioral studies of the olivocochlear efferent system: learning to listen in
      noise.
AB  - BACKGROUND: Olivocochlear (OC) neurons make up an efferent, descending auditory
      system that returns sound representations to the inner ear soon after they have
      entered the brain. Efferent inputs into the cochlea modulate outer hair cell
      activity to improve the neural encoding of auditory signals in background noise.
      Based on this physiological evidence, loss of efferent feedback is expected to
      degrade perception in noise. Attempts to confirm this prediction with long-term
      audiological assessments have met with mixed results. OBJECTIVE: To isolate
      procedural factors that may diminish the demonstration of long-term OC deficits
      in listening tasks. DESIGN: Operant conditioning procedures were used to train
      domestic cats to signal a change in the location of an auditory stimulus by
      responding on a lever. The smallest detectable change in location was measured by
      manipulating the distance between speakers under quiet conditions and in the
      presence of background noise. Functional consequences of efferent feedback were
      evaluated by comparing the sound localization thresholds of OC-lesioned cats with
      normal controls. RESULTS: As predicted by the hypothesized function of OC
      feedback systems, the lesioned cats exhibited significantly elevated thresholds
      only when tested in background noise. This initially poor performance returned to
      normal values after long-term exposure to the testing procedure. CONCLUSIONS: The
      results of our animal studies support the OC enhancement of sound localization
      behavior in background noise. Also, our behavioral observations suggest the
      acquisition of alternate listening strategies that allowed lesioned cats to
      minimize the functional consequences of their auditory deficits by attending more
      closely to remaining directional cues. These learned compensatory behaviors were
      encouraged by our present experimental design, which incorporated long-term
      training under consistent stimulus conditions. These findings point out the
      potential limitations of the highly routine audiological procedures that have
      been used to assess the impact of OC feedback on human hearing.

PMID- 15148197
TI  - Massive endolymphatic sac and vestibular aqueduct in Mondini dysplasia.
AB  - A postmortem study was performed on the bilateral temporal bones of a 90-year-old
      woman who had a lifelong profound hearing impairment. The histopathologic
      findings included severe Mondini dysplasia with unusual enlargement of the
      vestibular aqueducts and endolymphatic sacs. Dehiscent carotid arteries and
      dehiscent facial nerves were also present. The clinical and surgical aspects of
      the case are discussed based on the histopathologic findings. The physician
      should be prepared to diagnose congenital hearing impairment promptly to avoid
      complications during the clinical and surgical treatment of patients with Mondini
      dysplasia.

PMID- 15148199
TI  - Single versus three piece acrylic IOLs.

PMID- 15148200
TI  - Childhood vision impairment.

PMID- 15148201
TI  - Babbage the unfortunate.

PMID- 15148202
TI  - A comparison of anterior and posterior chamber lenses after cataract extraction
      in rural Africa: a within patient randomised trial.
AB  - BACKGROUND: Extracapsular cataract extraction (ECCE) with a posterior chamber
      intraocular lens (PC IOL) is the preferred method of cataract surgery in
      developed countries. However, intracapsular cataract extraction (ICCE) with an
      anterior chamber lens (AC IOL) may be appropriate in rural Africa. A randomised
      controlled trial was carried out to compare these surgical strategies. METHODS:
      Participants over 50 years requiring bilateral cataract surgery were recruited
      from outreach clinics in rural north and east Uganda. One eye was randomly
      allocated to AC IOL or PC IOL, the other eye being allocated to the second
      strategy. The main outcome measure was WHO distance visual acuity (VA) category
      after a minimum of 1 year. Secondary outcomes were numbers and causes of
      complications and refractive corrections. RESULTS: Of the 110 participants
      recruited, 98 (89%) were assessed at least 1 year after the operation (median
      follow up 17.5 months). Nine eyes randomised to PC IOL were converted to AC IOL;
      one eye randomised to AC IOL inadvertently received PC IOL. There was no
      difference in VA between 95 pairs of eyes for which data for both eyes were
      available (uncorrected VA, p = 0.26; corrected VA, p = 0.59). 80 (82%, 95% CI 73
      to 89) and 82 (84%, 95% CI 75 to 90) eyes randomised to AC IOL and PC IOL
      respectively had corrected VA of 6/18 or better. 16 (16%, 95% CI 10 to 25) and
      eight (8%, 95% CI 4 to 15) eyes respectively had secondary procedures or other
      complications. CONCLUSIONS: Where both strategies are available, ECCE with PC IOL
      should be first choice because of fewer complications. Where ECCE with PC IOL is
      not immediately feasible, ICCE with AC IOL is an acceptable interim technique.

PMID- 15148203
TI  - The prevalence and causes of visual impairment in Tehran: the Tehran Eye Study.
AB  - AIMS: To determine the prevalence and causes of visual impairment in Tehran,
      Iran, through a population based study. METHODS: In a population based, cross
      sectional study, 6497 Tehran citizens were sampled from 160 clusters using a
      stratified, random, cluster sampling strategy. The eligible people were
      enumerated through a door to door household survey in the selected clusters and
      were invited. All participants were transferred to a clinic for an extensive eye
      examination and interview. Visual impairment was determined using presenting and
      best corrected visual acuity (low vision: visual acuity of less than 6/18 to 3/60
      in the better eye; blindness: visual acuity of less than 3/60 in the better eye).
      RESULTS: Of those sampled, 4565 (70.3%) people participated in the study. The age
      and sex standardised prevalences of visual impairment on the basis of best
      corrected and presenting visual acuity were 1.39% (95% confidence interval (CI),
      1.07 to 1.71) and 2.52% (95% CI, 2.07 to 2.97), respectively. 15 people (0.28%;
      95% CI, 0.14 to 0.42) were blind with corrected vision while 22 (0.39%; 95% CI,
      0.23 to 0.56) were blind with presenting vision. Using the corrected and
      presenting vision, the prevalence of low visual impairment was 1.11% (95% CI,
      0.84 to 1.39) and 2.13% (95% CI, 1.71 to 2.55), respectively. The causes of
      visual impairment according to the best corrected vision were cataract (36.0%),
      macular degeneration (20.0%), and amblyopia (10.7%). However, according to the
      presenting vision, uncorrected refractive errors were the most frequent primary
      cause (33.6%) and cataract (25.4%), macular degeneration (12.7%), and amblyopia
      (8.2%) were the other main causes of visual impairment in the study sample. The
      prevalence of visual impairment was associated with advancing age and lower
      education. CONCLUSION: The results indicate that the burden of visual impairment
      is important and, although easily preventable, uncorrected refractive errors and
      cataract have a major role as causes of visual impairment in this population.
      Results also highlight the need for visual impairment prevention programmes, with
      emphasis on treatment of refractive errors and cataract.

PMID- 15148204
TI  - A prospective, randomised comparison of single and three piece acrylic foldable
      intraocular lenses.
AB  - AIMS: To compare the postoperative performance of single and three piece acrylic
      foldable intraocular lenses (IOLs). METHODS: 20 patients underwent bilateral
      cataract surgery with a single piece SA30AL IOL in one eye and a three piece
      MA30BA IOL in the other eye. The eyes were randomly assigned to either a single
      or three piece lens. The amount of IOL decentration and tilt, area of anterior
      capsule opening, and degree of posterior capsule opacification were measured
      using the Scheimpflug anterior segment analysis system (Nidek EAS-1000). Visual
      acuity and contrast sensitivity were examined. Measurements were performed by
      masked examiners before and 1 day, 1 week, 1, 3, 6, and 18 months after surgery.
      RESULTS: There were no significant differences between the two groups (p>0.05,
      paired t test) in the amount of IOL decentration, IOL tilt, area of anterior
      capsule opening, degree of posterior capsule opacification, best corrected visual
      acuity, and contrast sensitivity throughout the 18 month follow up period.
      CONCLUSION: The single and three piece acrylic foldable IOLs are equally stable
      in the eye after surgery.

PMID- 15148205
TI  - Pesky trachoma suspect finally caught.
AB  - AIM: Face seeking flies have long been thought to transmit Chlamydia trachomatis,
      the causative agent of trachoma, but this has never been proven. The four
      criteria proposed by Barnett, previously used to incriminate other arthropods
      suspected of transmitting disease, were examined. One of these criteria remains
      unmet: the repeated demonstration of the presence of C trachomatis on flies. The
      authors used polymerase chain reaction (PCR) to look for the presence of C
      trachomatis DNA on flies in the Gurage Zone of Ethiopia. METHODS: Using sticky
      paper, one fly was collected from the face of each of 103 children aged 1-10
      years. The piece of fly paper to which the fly was attached was cut out, followed
      by the collection of an empty piece from an arbitrary area of the fly paper,
      which served as control. Roche Amplicor PCR kits were used to detect C
      trachomatis DNA. RESULTS: Evidence of C trachomatis by PCR was found on 15 of 103
      flies versus 0 of 103 controls (p = 0.0001). CONCLUSION: These results meet the
      final criterion needed to incriminate flies as a vector of trachoma. However,
      interventional studies will be needed to show the importance of fly control.

PMID- 15148207
TI  - Nitric oxide proxies and ocular perfusion pressure in primary open angle
      glaucoma.
AB  - BACKGROUND: To investigate the levels of nitric oxide (NO) markers in plasma and
      aqueous humour of patients with primary open angle glaucoma (POAG) and their
      relation to ocular perfusion pressure. METHODS: Cyclic guanosine monophosphate
      (cGMP) and nitrite (NO(2)(-)) were determined in plasma and aqueous humour of 38
      patients with POAG and 46 controls. Blood pressure and IOP were measured to
      calculate ocular perfusion pressure (PP). RESULTS: cGMP and NO(2)(-) plasma
      levels were significantly decreased in glaucoma patients compared with controls
      (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and
      NO(2)(-) concentrations were also lower than in normal eyes (p = 0.0001 v p =
      0.001). There was a linear association between cGMP in plasma and aqueous humour
      in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and
      this relation differed in the two groups (p = 0.003). Considering glaucoma
      patients with controls, a positive correlation was found between cGMP and PP (r =
      0.379, p = 0.01) and between NO(2)(-) and PP (r = 0.339, p = 0.040). The cGMP/PP
      correlation was of borderline statistical significance in controls (p = 0.050),
      whereas it did not attain statistical significance in POAG, as well as the
      association between NO(2)(-) and PP when glaucomas and controls were considered
      separately. CONCLUSIONS: The authors found alterations of NO markers in the
      plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO
      balance could alter ocular perfusion pressure.

PMID- 15148206
TI  - A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion
      mutation in 2B domain of keratin 12 gene associated with Meesmann's corneal
      dystrophy.
AB  - AIM: To determine the disease causing gene defects in two patients with
      Meesmann's corneal dystrophy. METHODS: Mutational analysis of domains 1A and 2B
      of the keratin 3 (K3) and keratin 12 (K12) genes from two patients with
      Meesmann's corneal dystrophy was performed by polymerase chain reaction
      amplification and direct sequencing. RESULTS: Novel mutations of the K12 gene
      were identified in both patients. In one patient a heterozygous point mutation
      (429A-->C = Arg135Ser) was found in the 1A domain of the K12 gene. This mutation
      was confirmed by restriction digestion. In the second patient a heterozygous 27
      bp duplication was found inserted in the 2B domain at nucleotide position 1222
      (1222ins27) of the K12 gene. This mutation was confirmed by gel electrophoresis.
      The mutations were not present in unaffected controls. CONCLUSION: Novel K12
      mutations were linked to Meesmann's corneal dystrophy in two different patients.
      A missense mutation replacing a highly conserved arginine residue in the
      beginning of the helix initiation motif was found in one patient, and an
      insertion mutation, consisting of a duplication of 27 nucleotides, was found
      before the helix termination motif in the other.

PMID- 15148208
TI  - Optic nerve head morphometry in healthy adults using confocal laser scanning
      tomography.
AB  - BACKGROUND/AIMS: To study the optic nerve head (ONH) characteristics in a cross
      sectional study with confocal laser scanning tomography using the Heidelberg
      retina tomograph (HRT I) and thereby to obtain a new HRT database for comparison
      of healthy and glaucomatous eyes. METHODS: White adults with no history of ocular
      pathology were eligible for the study. The examination comprised: assessment of
      visual acuity; slit lamp examination of the anterior and posterior segment;
      Goldmann applanation tonometry; computerised perimetry, and optic nerve head
      tomography with HRT. Eyes with ocular pathology were excluded. Mean (standard
      deviation, SD) and difference between right and left eye (RE-LE) were calculated
      for HRT I measurements. Differences in mean topographic parameters between male
      and female participants and between the age quartiles were analysed. The study
      included 1764 eyes of 882 healthy adults (154 females and 728 males, mean age of
      46.8 (SD 8.6) years). The population investigated was larger and older in
      comparison with similar studies using confocal laser scanning tomography.
      RESULTS: With HRT I, a mean disc area of 1.82 (SD 0.39) mm(2), a mean cup area of
      0.44 (SD 0.32) mm(2) and a mean cup:disc area ratio of 0.22 (SD 0.13) was
      observed. Right eyes showed a larger mean retinal nerve fibre layer thickness
      (RNFLT) (0.263 (SD 0.066) mm) compared with left eyes (0.252 (SD 0.065) mm,
      p<0.001). Higher values in younger volunteers (mean age 35.7 years) in comparison
      with elderly participants (mean age 59.1 years) were noted for disc area (1.84
      mm(2)v 1.78 mm2) and mean RNFLT (0.263 (SD 0.06) mm v 0.249 (SD 0.07) mm) but
      were not significant (p>0.01). The presented results differ from published data
      on ONH measurements of healthy volunteers with different techniques. CONCLUSION:
      The observed differences in ONH measurements between left and right eyes seem not
      to be of clinical importance. This is also true for age or sex dependent changes
      in ONH topographies. The presented data provide a new basis for comparison of
      optic disc characteristics between healthy eyes and glaucomatous eyes.

PMID- 15148209
TI  - The effect of optic disc diameter on vertical cup to disc ratio percentiles in a
      population based cohort: the Blue Mountains Eye Study.
AB  - OBJECTIVE: The 97.5th percentile for vertical cup to disc ratio (VCDR) has been
      proposed as a useful tool to assist in the diagnosis of glaucoma in population
      studies. Previous reports of VCDR percentiles have either not been adjusted for
      disc size or have been calculated by regression analysis from small hospital
      based cohorts. The authors' aim was to generate VCDR percentiles in a large,
      population based sample. METHODS: Data were collected from 3654 individuals, aged
      49 years or older, living in the Blue Mountains, west of Sydney. Vertical disc
      diameter and VCDR were determined by planimetry from stereo optic disc
      photographs. The distribution of VCDR and percentiles (95th, 97.5th, 99th) were
      calculated. RESULTS: 6678 eyes were included in the analysis. Median cup to disc
      ratio, 95th, 97.5th, and 99th percentile increased with vertical optic disc
      diameter in a linear fashion. An increase of 0.2 in median VCDR (0.35 to 0.55)
      was observed between small (1.1-1.3 mm) and large (1.8-2.0 mm) optic discs. An
      equivalent increase of 0.2 (0.59 to 0.74) was observed for the 97.5th percentile
      from small to large discs. CONCLUSION: VCDR percentiles for a "normal"
      population, adjusted for vertical optic disc diameter are presented. One quarter
      of all discs fell within the small or large disc categories highlighting the
      importance for estimating optic disc size. These data may assist in the diagnosis
      of glaucoma in clinical practice as well as providing a normative database. Sole
      use of VCDR percentile cut offs in defining glaucoma cases in population surveys
      requires further validation.

PMID- 15148210
TI  - Diameter variations of retinal blood vessels during and after treatment with
      hyperbaric oxygen.
AB  - AIMS: To quantify retinal vascular change during and after hyperbaric oxygenation
      (HO) for 6x5 weekly 90 minute treatments. METHODS: Fundus photographs were taken
      before, during, and after HO at 2.5 atmospheres absolute pressure (ATA) on days
      1, 2, 3, 10, 20, 29, and 30 of treatment on three patients using a specially
      developed hand held ophthalmoscope with a digital colour camera. Blood vessel
      diameter was estimated on red free retinal images. The mean of three measurements
      of arterioles and venoles close to the optic disc was calculated. Consistency and
      repeatability of the method was verified by estimating the diameter of the
      vessels by three measurements in each of seven images taken within 70 seconds on
      the same person. Analysis of variance with Bonferroni correction for multiple
      comparisons was conducted to ascertain whether significant intergroup differences
      existed. RESULTS: Breathing 100% oxygen at 2.5 ATA constricts retinal arterioles
      by 9.6% (standard deviation 0.3%) and venoles by 20.6% (SD 0.3%) of their size in
      air at ambient pressure. Constriction escalates during treatment. Ten minutes
      after the HO, arterioles dilate to 94.5% (SD 0.3%) and venoles to 89.0% (SD 0.3%)
      of their primary size. This pattern is the same for each day of measurement.
      Heart frequency falls continually during HO. Systolic, diastolic, and mean
      arterial pressures stay constant. CONCLUSION: Exposure to hyperbaric oxygen
      causes constriction of the retinal vessels. It is found that this constriction is
      constant through the series of treatments. This suggests that oxygen or products
      thereof are responsible for the vascular changes during and after hyperbaric
      oxygenation probably through autoregulation of the retinal vessels.

PMID- 15148211
TI  - Response of choroidal blood flow to carbogen breathing in smokers and non
      smokers.
AB  - AIM: To investigate a potential difference in ocular vascular reactivity during
      carbogen breathing in optic nerve head, choroid, and retina between healthy
      smokers and non-smokers. METHODS: 25 (13 smokers and 12 non-smokers) healthy male
      volunteers participated in this observer masked, two cohort study. During
      inhalation of carbogen (5% CO(2) and 95% O(2)) over 10 minutes measurements were
      taken using laser Doppler flowmetry to assess submacular choroidal and optic
      nerve head blood flow, laser interferometry to assess fundus pulsation
      amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters.
      RESULTS: At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in
      smokers than in non-smokers. During administration of carbogen the response in
      choroidal blood flow was significantly different between the two groups: there
      was an increase in non-smokers after carbogen breathing (p = 0.048) compared with
      relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A
      similar response pattern was seen for fundus pulsation amplitude, which increased
      notably after carbogen breathing in non-smokers but not in smokers (p<0.001
      between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters
      were reduced in both groups to a comparable degree during carbogen breathing.
      CONCLUSION: The study indicated abnormal choroidal vascular reactivity in chronic
      smokers. These early haemodynamic changes may be related to the increased risk to
      smokers of developing ocular vascular diseases. The specific mechanisms
      underlying abnormal choroidal vascular reactivity in chronic smokers remain to be
      characterised.

PMID- 15148212
TI  - Engaging families in health services research on childhood visual impairment:
      barriers to, and degree and nature of bias in, participation.
AB  - AIM: To investigate the barriers to, and degree and nature of bias in,
      participation in health services research by parents of children with visual
      impairment. METHODS: Parents of children newly diagnosed with ophthalmic
      disorders at Great Ormond Street Hospital, London, participated in a study to
      elicit their health service experiences and needs through a postal questionnaire
      survey followed by in-depth interviews. The participating and non-participating
      families were compared at different stages of recruitment, according to
      sociodemographic and clinical characteristics. RESULTS: 20% (55) of all eligible
      families could not be invited to participate because of out of date contact
      details for either the family and/or family doctor in the hospital and/or
      community record systems. Completed questionnaires were received from 67%
      (147/221) of contacted families, although only 6% actively declined to take part.
      Compared to non-participating parents, those who took part were more likely to be
      white British, from higher socioeconomic groups, have English as their main
      language, and have no other visually impaired family members. There were no
      significant differences according to the clinical characteristics of their
      affected children. CONCLUSIONS: Families from socioeconomically deprived and
      ethnic minority groups are likely to be less visible than others in health
      services research on childhood visual impairment. Geographical mobility in
      families of young children with visual disability poses a potentially important
      obstacle to engaging them in research on their experiences of health services.
      These findings indicate the importance of addressing potential biases in the
      design and interpretation of future studies, to ensure equity in recommendations
      for policy and practice, and in implementation of services.

PMID- 15148213
TI  - The relation between disease asymmetry and severity in keratoconus.
AB  - BACKGROUND/AIM: Keratoconus is described as a bilateral, asymmetric, non
      inflammatory corneal ectasia. The purpose of the study was to examine the
      relation between disease asymmetry and severity in the Collaborative Longitudinal
      Evaluation of Keratoconus (CLEK) Study cohort. METHODS: Analyses included 1037
      keratoconus patients from the CLEK Study baseline examination visit, none of whom
      had undergone corneal surgery in either eye. Disease asymmetry was determined by
      taking the difference between eyes for continuous variables. For categorical
      variables, asymmetry was categorised by whether the variable was present in
      neither, one, or both eyes. Disease severity was defined using the first definite
      apical clearance lens (FDACL) technique (a rigid contact lens to measure corneal
      curvature) from the worse (steeper) eye. Statistical analyses included Pearson's
      correlation coefficients (continuous variables) and analysis of variance
      (categorical variables). RESULTS: There were generally weak correlations between
      asymmetry and severity for low contrast habitual visual acuity (r = 0.12, p =
      0.0003), high contrast habitual visual acuity (r = 0.14, p<0.0001), low contrast
      best corrected visual acuity (r = 0.21, p<0.0001), and high contrast best
      corrected visual acuity (r = 0.29, p<0.0001). Asymmetry in refractive error was
      more moderately correlated with disease severity (r = 0.41, p<0.0001), as was
      asymmetry in the flat (r = 0.61, p<0.0001) and steep keratometric readings (r =
      0.54, p<0.0001). The average FDACL was significantly steeper in patients who had
      one eye with Vogt's striae, Fleischer's ring, or corneal scarring compared with
      the average FDACL when neither eye had these findings. CONCLUSION: Keratoconus
      patients with more severe disease are also more asymmetric in their disease
      status.

PMID- 15148214
TI  - Effect of laser treatment for dry age related macular degeneration on foveolar
      choroidal haemodynamics.
AB  - AIM: Previous studies have suggested that laser photocoagulation therapy is
      associated with the resolution of drusen in some age related macular degeneration
      (AMD) patients. The main aim of the study was to determine whether low intensity
      laser treatment applied according to the Complications of AMD Prevention Trial
      (CAPT) protocol produces changes in the choroidal circulation that may help
      explain the mechanism leading to the resolution of drusen material. METHODS: This
      ancillary study included 30 CAPT patients with bilateral drusen that were treated
      and followed at the University of Pennsylvania. Laser Doppler flowmetry was used
      to measure relative choroidal blood velocity (Ch(vel)), volume (Ch(vol)), and
      flow (Ch(flow)) in the centre of the fovea. Measurements were obtained through a
      dilated pupil in both eyes of each patient at the initial CAPT visit before laser
      treatment was applied in one eye. Measurements were repeated in both eyes of each
      subject three months later. Analysis of laser Doppler measurements was performed
      in a masked fashion. RESULTS: In comparison to baseline, no significant
      differences in Ch(vel), Ch(vol), or Ch(flow) were observed three months following
      the application of low intensity laser according to the CAPT protocol in the
      untreated and treated eyes. In comparison to the untreated eyes, no significant
      differences were detected in the treated eyes. Based on the variability of flow
      measurements in the untreated eyes, the authors estimated an 85% power to detect
      a 15% change in relative blood flow. CONCLUSIONS: The results suggest that large
      alterations in choroidal blood flow do not occur at three months after low
      intensity laser therapy following the CAPT protocol.

PMID- 15148215
TI  - Torsional optokinetic nystagmus: normal response characteristics.
AB  - BACKGROUND/AIMS: Few studies have investigated normal response characteristics of
      torsional optokinetic nystagmus (tOKN). The authors have investigated the effect
      of stimulus velocity and central/peripheral stimulation on tOKN. METHODS:
      Torsional OKN was elicited using a sinusoidal grating rotating at velocities of 3
      degrees /s to 1000 degrees /s in clockwise and anticlockwise directions. To
      investigate the effect of central stimulation, stimulus size was varied from 2.86
      degrees to 50.8 degrees. An artificial scotoma placed over a 50.8 degrees
      stimulus was varied from 2.86 degrees to 43.2 degrees to investigate peripheral
      stimulation. Eight subjects participated in each experiment and torsional eye
      movements were recorded using video-oculography. The mean slow phase velocity
      (MSPV) and gain were calculated. RESULTS: The maximum gain occurred in response
      to 8 degrees /s stimulation. The MSPV increased up to a stimulus velocity of 200
      degrees /s achieving a maximum of 3 degrees /s in both directions. MSPV was
      linearly correlated with the log of stimulus velocity. The smallest field size,
      rotating at 40 degrees /s, evoked 10% of the gain elicited by the largest
      display. When the most peripheral stimulus was used, the gain was maintained at
      50% of the gain evoked when the full display was used. CONCLUSIONS: A wide range
      of stimulus velocities can elicit tOKN and peripheral field stimulation
      contributes significantly to its response.

PMID- 15148216
TI  - Thyroid associated ophthalmopathy: evidence for CD4(+) gammadelta T cells; de
      novo differentiation of RFD7(+) macrophages, but not of RFD1(+) dendritic cells;
      and loss of gammadelta and alphabeta T cell receptor expression.
AB  - AIM: To characterise periorbital immune cells (stages, kinetics) in active and
      inactive thyroid associated ophthalmopathy (A-TAO; I-TAO). METHODS: In orbital
      tissue cryosections of patients with A-TAO (n = 15), I-TAO (n = 11), and healthy
      controls (n = 14), adipose and fibrovascular areas were evaluated for MHC II(+)
      cells, CD45(+) total leukocytes, myeloid cells (CD33(+) monocytes; CD14(+)
      macrophages; mature RFD7(+) macrophages; RFD1(+) dendritic cells (DCs)), and
      lymphoid cells (CD4(+) T cells; alphabeta and gammadelta T cells; CD20(+) B
      cells). Results are expressed as medians and 5% confidence intervals. RESULTS: In
      fibrovascular septae, a surge of CD33(+) immigrants clearly correlating with
      disease activity generated significantly increased (p<0.05) percentages of
      CD14(+) and RFD7(+) macrophages. Intriguingly, CD4(+) cells were mostly
      gammadelta T cells, while alphabeta T helper cells were much less frequent.
      Successful treatment rendering TAO inactive apparently downregulates monocyte
      influx, macrophage differentiation, and T cell receptor expression. Similar
      trends were recorded for adipose tissue. Interestingly, RFD1(+) DCs were
      completely absent from all conditions examined. CONCLUSION: A-TAO coincides with
      periorbital monocyte infiltration and de novo differentiation of macrophages, but
      not DCs. The authors discuss a novel potential role for inflammatory CD4(+)
      gammadelta T cells in TAO. Successful treatment apparently downregulates orbital
      monocyte recruitment and effects functional T cell knockout.

PMID- 15148217
TI  - Expression of pigment epithelium derived factor and vascular endothelial growth
      factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy.
AB  - AIMS: To determine whether pigment epithelium derived factor (PEDF), a protein
      that inhibits angiogenesis, is expressed in human choroidal neovascular membranes
      (CNVMs) and in tissues from an eye with polypoidal choroidal vasculopathy (PCV).
      In addition, to compare the expression of PEDF with that of vascular endothelial
      growth factor (VEGF), a known stimulator of angiogenesis, in these tissues.
      METHODS: CNVMs, associated with age related macular degeneration (AMD), angioid
      streaks, and PCV, were obtained during surgery. The expression of PEDF and VEGF
      in the excised subretinal fibrovascular membranes was determined by
      immunohistochemistry. RESULTS: PEDF and VEGF were strongly expressed in the
      vascular endothelial cells and retinal pigment epithelial (RPE) cells in the
      CNVMs where numerous new vessels were prominent (clinically active CNVMs). On the
      other hand, immunoreactivity for PEDF and VEGF was weak in the new vessels where
      fibrosis was prominent (clinically quiescent CNVMs). However, the RPE cells were
      still positive for PEDF and VEGF. The specimens from the eye with PCV also showed
      strong expression of PEDF and VEGF in the vascular endothelial cells and the RPE
      cells. CONCLUSION: Because PEDF is an inhibitor of ocular angiogenesis and an
      inhibitor of ocular cell proliferation, our results suggest that PEDF along with
      VEGF may modulate the formation of subfoveal fibrovascular membranes.

PMID- 15148218
TI  - Hypoglycaemia exacerbates ischaemic retinal injury in rats.
AB  - AIMS: To determine the effect of hypoglycaemia on ischaemic retinal injury.
      METHODS: Rat retinal cultures were incubated in varying concentrations of glucose
      while placed under standardised anoxic conditions, and the number of surviving
      GABA immunoreactive neurons was assessed using immunocytochemistry. Hypoglycaemia
      was induced in age and sex matched Wistar rats by an injection of rapid acting
      insulin. The blood, vitreous, and retinal glucose concentrations were measured
      using a hexokinase assay kit. Electroretinography, semiquantitative RT-PCR, and
      histology were used to compare the functional and structural retinal injury in
      these rats with the injury in appropriate controls after a period of pressure
      induced retinal ischaemia. RESULTS: Retinal cultures maintained in low glucose
      concentrations (<1 mM) had fewer surviving GABA immunoreactive neurons after an
      anoxic insult compared with retinal cultures maintained in 5 mM glucose.
      Hypoglycaemic rats had significantly lower vitreous glucose concentrations (0.57
      (SEM 0.04) mM) than the control rats (3.1 (0.70) mM; p<0.001). The a-wave and b
      wave amplitudes of the hypoglycaemic rats after 3 and 7 days of reperfusion were
      significantly lower than the amplitudes of the control rats. Furthermore, the
      level of Thy-1 mRNA (a retinal ganglion cell marker) was significantly lower in
      the hypoglycaemic group (p<0.001) and there was a corresponding exacerbation of
      structural injury compared with the controls. CONCLUSION: Hypoglycaemia causes a
      significant reduction in vitreous glucose levels and exacerbates ischaemic
      retinal injury.

PMID- 15148219
TI  - Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal
      epithelial cells in vitro.
AB  - PURPOSE: Sodium hyaluronate (hyaluronic acid) is known to promote corneal
      epithelial wound healing in vivo and in vitro, in animal experiments. Sodium
      hyaluronate is the ligand for CD44, a cell surface adhesion molecule which has
      been found on normal human corneal epithelial cells. The purpose of this study
      was to investigate the effect of sodium hyaluronate on human corneal epithelial
      cell migration, proliferation, and CD44 receptor expression. METHODS: Human
      corneal epithelial cell cultures were established from 32 donor corneoscleral
      rims and maintained separately in three different culture conditions: (1) culture
      medium only, (2) sodium hyaluronate enriched (0.6 mg/ml) medium, and (3)
      hydroxypropylmethylcellulose enriched (2.5 mg/ml) medium. The total area of
      migrating epithelial cell sheets in each case was measured by planimetry on days
      4, 8, 12, and 16. Cytospin preparations of cells cultured in the different
      culture conditions were examined immunohistochemically for proliferation and CD44
      receptor expression using antibodies directed against Ki67 and CD44 respectively.
      RESULTS: Cells cultured in the presence of sodium hyaluronate showed
      significantly increased migration at days 12 and 16 (Friedmen test: p = 0.0012,
      day 16; p = <0.001, day 12) compared with cells cultured in the other media.
      There was no difference in cell proliferation (Ki67) or CD44 expression on cells
      cultured in the different culture conditions. CONCLUSIONS: Sodium hyaluronate
      promotes migration but not proliferation or CD44 expression on human corneal
      epithelial cells in vitro. The beneficial effect of sodium hyaluronate in corneal
      wound healing is likely to be related to rapid migration of cells leading to
      rapid wound closure. This may be facilitated by the adhesion between CD44 on the
      cells and hyaluronic acid, which coats the surface of the denuded cornea.

PMID- 15148220
TI  - Application of femtosecond ultrashort pulse laser to photodynamic therapy
      mediated by indocyanine green.
AB  - BACKGROUND/AIMS: To evaluate treatment with high peak power pulse energy by
      femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800
      nm wavelength for corneal neovascularisation using photodynamic therapy (PDT)
      mediated by indocyanine green (ICG). METHODS: Using a gelatin solid as an in
      vitro corneal model, the safety of laser power was studied to determine if it
      degenerated gelatin with or without ICG. The authors then induced corneal
      neovascularisation in rabbit eyes by an intracorneal suturing technique.
      Fluorescein angiography was used to evaluate occlusion before PDT and 0, 1, 3,
      and 10 days after PDT. The authors performed light microscopy with haematoxylin
      eosin staining and transmission electron microscopy to determine thrombosis
      formation in the neovascular regions. RESULTS: The threshold of peak laser power
      density ranged from 39 to 53 W/cm(2). Laser irradiation was started 30 seconds
      after a 10 mg/kg ICG injection, and all irradiated segments were occluded at 0,
      1, 3, and 10 days at 3.8 J/cm(2). Light and electron microscopy documented
      thrombosis formation in the neovascular region. CONCLUSION: Femtosecond pulse
      laser enhanced by ICG can be used for PDT. Because of effective closure of
      corneal neovascularisation at a low energy level, the high peak power pulse
      energy of the femtosecond pulse laser might be more efficacious than continuous
      wave laser for use with PDT.

PMID- 15148221
TI  - Strabismus surgery in the management of diplopia caused by myasthenia gravis.

PMID- 15148222
TI  - Orbital varices and orbital wall defects.

PMID- 15148223
TI  - Bovine pericardium (Ocuguard) wrap for hydroxyapatite implants.

PMID- 15148224
TI  - Cyclical esotropia following surgery for partially accommodative esotropia.

PMID- 15148225
TI  - Retinal progenitor cells in the posterior pars plana of rhesus monkeys.

PMID- 15148226
TI  - Angioid streaks in identical twins.

PMID- 15148227
TI  - Late recurrence of Langerhans cell histiocytosis in the orbit.

PMID- 15148228
TI  - Morphallaxia-like ocular histology after intravitreal triamcinolone acetonide.

PMID- 15148230
TI  - Retinal racemose haemangioma directly communicating with a intramuscular facial
      cavernous haemangioma.

PMID- 15148229
TI  - Photodynamic therapy for corneal neovascularisation and lipid degeneration.

PMID- 15148231
TI  - Pupil sparing excision of an atypical iris melanocytoma induces remission of
      secondary glaucoma.

PMID- 15148233
TI  - Pseudohypopyon after intravitreal triamcinolone injection for the treatment of
      pseudophakic cystoid macular oedema.

PMID- 15148232
TI  - Peripheral visual field loss following treatment with etanercept.

PMID- 15148234
TI  - Treatment of Erdheim-Chester disease with cladribine: a rational approach.

PMID- 15148235
TI  - Aspergillus keratitis following corneal foreign body.

PMID- 15148236
TI  - Partial resolution of acute ascending motor polyneuropathy after enucleation of
      an eye with metastatic melanoma.

PMID- 15148237
TI  - The clinical evolution of a kissing naevus after incomplete excision.

PMID- 15148238
TI  - Comments on confocal microscopy of Aspergillus fumigatus keratitis.

PMID- 15148239
TI  - Macular infarction after intravitreal amikacin.

PMID- 15148242
TI  - Water-soluble carbon monoxide-releasing molecules: helping to elucidate the
      vascular activity of the 'silent killer'.
AB  - Carbon monoxide (CO) is formed during the degradation of haeme by haeme oxygenase
      (HO). As well as being an important signalling molecule and vasodilator, CO also
      possesses antihypertensive, anti-inflammatory and antiapoptotic qualities and
      protects against ischaemic tissue injury. Several approaches have been used to
      investigate the therapeutic potential of CO, ranging from direct administration
      of CO gas to the use of prodrugs, which generate CO upon metabolism. A novel
      approach involves the use of specific CO carriers, which will release measurable,
      controllable and effective amounts of CO into biological systems. Transitional
      metal carbonyls based around iron, manganese or ruthenium have recently been
      developed as CO-releasing molecules (CO-RMs) that, under appropriate conditions,
      will release CO. Such molecules have been shown to provide cardioprotection in
      both ex vivo and in vivo experiments. To date, CO-RMs have been largely
      incompatible with biological systems in that they are only soluble in organic
      solvents or have to be preactivated either by physical or chemical stimuli.
      However, the recent development of water-soluble CO-RMs has provided new
      opportunities to investigate the pharmacological and biological features of CO
      without such confounding influences. CORM-3, a novel water-soluble CO-RM, has
      recently been used to confirm the cardioprotective actions of CO. In this issue
      of British Journal of Pharmacology, Foresti and co-workers report that CORM-3
      delivers CO, produces aortic vasodilation ex vivo and reduces blood pressure in
      vivo via modulation of the same cGMP and potassium channels utilised by
      endogenous and exogenous CO. These findings suggest that CORM-3 has the potential
      for use as a modulator of vascular function and hypertension. However, the use of
      water-soluble CO-RMs raises several questions of their own which will need to be
      addressed if CO-RMs are to be of future use therapeutically.

PMID- 15148241
TI  - 4-Chloro-benzo[F]isoquinoline (CBIQ) activates CFTR chloride channels and KCNN4
      potassium channels in Calu-3 human airway epithelial cells.
AB  - 1 Calu-3 cells have been used to investigate the actions of 4-chloro
      benzo[F]isoquinoline (CBIQ) on short-circuit current (SCC) in monolayers, whole
      cell recording from single cells and by patch clamping. 2 CBIQ caused a
      sustained, reversible and repeatable increase in SCC in Calu-3 monolayers with an
      EC50 of 4.0 microm. Simultaneous measurements of SCC and isotopic fluxes of 36Cl-
      showed that CBIQ caused electrogenic chloride secretion. 3 Apical membrane
      permeabilisation to allow recording of basolateral membrane conductance in the
      presence of a K+ gradient suggested that CBIQ activated the intermediate
      conductance calcium-sensitive K(+)-channel (KCNN4). Permeabilisation of the
      basolateral membranes of epithelial monolayers in the presence of a Cl- gradient
      suggested that CBIQ activated the Cl(-)-channel CFTR in the apical membrane. 4
      Whole-cell recording in the absence of ATP/GTP of Calu-3 cells showed that CBIQ
      generated an inwardly rectifying current sensitive to clotrimazole. In the
      presence of the nucleotides, a more complex I/V relation was found that was
      partially sensitive to glibenclamide. The data are consistent with the presence
      of both KCNN4 and CFTR in Calu-3. 5 Isolated inside-out patches from Calu-3 cells
      revealed clotrimazole-sensitive channels with a conductance of 12 pS at positive
      potentials after activation with CBIQ and demonstrating inwardly rectifying
      properties, consistent with the known properties of KCNN4. Cell-attached patches
      showed single channel events with a conductance of 7 pS and a linear I/V relation
      that were further activated by CBIQ by an increase in open state probability,
      consistent with known properties of CFTR. It is concluded that CBIQ activates
      CFTR and KCNN4 ion channels in Calu-3 cells.

PMID- 15148244
TI  - Hypericum perforatum L (St John's wort) preferentially increases extracellular
      dopamine levels in the rat prefrontal cortex.
AB  - The effects of hydro-alcoholic extracts of Hypericum perforatum L on
      extracellular serotonin (5-HT), noradrenaline (NA) and dopamine (DA) levels and
      the acidic metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid
      (HVA) and 5-hydroxy-3-indoleacetic acid (5-HIAA)) were examined by in vivo
      microdialysis in the prefrontal cortex of awake rats. Thus, a single dose (60 mg
      kg(-1) i.p. or 300 mg kg(-1) p.o.) of H. perforatum increased DA concentrations
      to 165 and 140% of control values, respectively, and increased locomotor activity
      in nonhabituated rats. DOPAC and HVA levels were markedly reduced. 5-HT
      concentrations were elevated only moderately, while the NA levels were not
      affected by any treatment. The whole-tissue analysis revealed that hypericum
      increased, whereas the monoamine oxidase (MAO) A/B inhibitor phenelzine decreased
      DA and 5-HT turnover. The present data indicate that the mechanism of action of
      hypericum extract in vivo is more complex than the inhibition of monoamine
      reuptake or metabolism observed in vitro. The finding of preferential enhancement
      of DA transmission is in agreement with human studies measuring DA-mediated
      neuroendocrine responses.

PMID- 15148243
TI  - Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing
      molecule.
AB  - 1 Carbon monoxide (CO), one of the end products of heme catabolism by heme
      oxygenase, possesses antihypertensive and vasodilatory characteristics. We have
      recently discovered that certain transition metal carbonyls are capable of
      releasing CO in biological fluids and modulate physiological functions via the
      delivery of CO. Because the initial compounds identified were not water soluble,
      we have synthesized new CO-releasing molecules that are chemically modified to
      allow solubility in water. The aim of this study was to assess the vasoactive
      properties of tricarbonylchloro(glycinato)ruthenium(II) (CORM-3) in vitro and in
      vivo. 2 CORM-3 produced a concentration-dependent relaxation in vessels
      precontracted with phenylephrine, exerting significant vasodilatation starting at
      concentrations of 25-50 microm. Inactive CORM-3, which does not release CO, did
      not affect vascular tone. 3 Blockers of ATP-dependent potassium channels
      (glibenclamide) or guanylate cyclase activity (ODQ) considerably reduced CORM-3
      dependent relaxation, confirming that potassium channels activation and cGMP
      partly mediate the vasoactive properties of CO. In fact, increased levels of cGMP
      were detected in aortas following CORM-3 stimulation. 4 The in vitro and in vivo
      vasorelaxant activities of CORM-3 were further enhanced in the presence of YC-1,
      a benzylindazole derivative which is known to sensitize guanylate cyclase to
      activation by CO. Interestingly, inhibiting nitric oxide production or removing
      the endothelium significantly decreased vasodilatation by CORM-3, suggesting that
      factors produced by the endothelium influence CORM-3 vascular activities. 5 These
      results, together with our previous findings on the cardioprotective functions of
      CORM-3, indicate that this molecule is an excellent prototype of water-soluble CO
      carriers for studying the pharmacological and biological features of CO.

PMID- 15148245
TI  - Drosophila melanogaster GRD and LCCH3 subunits form heteromultimeric GABA-gated
      cation channels.
AB  - In addition to its action as a fast inhibitory neurotransmitter, gamma
      aminobutyric acid (GABA) is thought to mediate excitatory action by activating
      cation currents in some cell types in invertebrates. However, to date no GABA
      receptor capable of mediating such action has been identified at the molecular
      level in insects. Using a systematic expression screening approach, we found that
      the Drosophila ligand-gated ion channel subunits GRD and LCCH3 combine to form
      cation-selective GABA-gated ion channels when coexpressed in Xenopus laevis
      oocytes. The heteromultimeric receptor is activated by GABA (EC50=4.5 microm),
      muscimol (EC50=4.8 microm) and trans-4-aminocrotonic acid (EC50=104.5 microm),
      and partially by cis-4-aminocrotonic acid (EC50=106.3 microm). Picrotoxin
      effectively blocked the GABA-gated channel (IC50=0.25 microm), but bicuculline,
      TPMTA, dieldrin and lindane did not. The benzodiazepines flunitrazepam and
      diazepam did not potentiate the GABA-evoked current. Our data suggest that
      heteromultimeric channels composed of GRD and LCCH3 subunits form GABA-gated
      cation channels in insects.

PMID- 15148246
TI  - 3',4'-Dihydroxyflavonol reduces infarct size and injury associated with
      myocardial ischaemia and reperfusion in sheep.
AB  - 1 The antioxidant properties of flavonols in vivo and their potential benefits in
      myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We
      evaluated the ability of a synthetic flavonol, 3',4'-dihydroxyflavonol (DiOHF) to
      scavenge superoxide in post-I/R myocardium and to prevent myocardial I/R injury.
      2 Anaesthetized sheep were studied in four groups (n=5-6): control, ischaemic
      preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg(-1), i.v.).
      The left anterior descending coronary artery was occluded distal to the second
      diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial
      function, NADPH-activated superoxide generation and biochemical markers of injury
      were measured. 3 DiOHF (10(-8)-10(-4) m) incubated in vitro with post-I/R
      myocardium from the vehicle group suppressed superoxide production dose
      dependently. 4 DiOHF administered in vivo also significantly reduced superoxide
      generation in vitro. DiOHF and IPC markedly reduced infarct size, which was 73+/
      2% of the area at risk in vehicle, 50+/-4% in DiOHF, 75+/-5% in control and 44+/
      4% in IPC. Post-I/R segment shortening within the ischaemic zone was greater in
      DiOHF (2.3+/-0.7%; P<0.01) and IPC (1.7+/-0.5%; P<0.01) than those in
      corresponding controls (-1.7+/-0.4; -2.1+/-0.4%). 5 DiOHF and IPC improved
      coronary blood flow to the ischaemic area and preserved higher levels of nitric
      oxide metabolites in the venous outflow from the ischaemic zone. 6 DiOHF
      attenuated superoxide production in post-I/R myocardium, and significantly
      reduced infarct size and injury following I/R in anaesthetized sheep. The extent
      of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has
      clinical potential for improving recovery from acute myocardial infarction and
      other ischaemic syndromes.

PMID- 15148247
TI  - Nitric oxide-dependent modulation of the delayed rectifier K+ current and the L
      type Ca2+ current by ginsenoside Re, an ingredient of Panax ginseng, in guinea
      pig cardiomyocytes.
AB  - 1 Ginsenoside Re, a major ingredient of Panax ginseng, protects the heart against
      ischemia-reperfusion injury by shortening action potential duration (APD) and
      thereby prohibiting influx of excessive Ca2+. Ginsenoside Re enhances the slowly
      activating component of the delayed rectifier K+ current (IKs) and suppresses the
      L-type Ca2+ current (I(Ca,L)), which may account for APD shortening. 2 We used
      perforated configuration of patch-clamp technique to define the mechanism of
      enhancement of IKs and suppression of I(Ca,L) by ginsenoside Re in guinea-pig
      ventricular myocytes. 3 S-Methylisothiourea (SMT, 1 microm), an inhibitor of
      nitric oxide (NO) synthase (NOS), and N-acetyl-L-cystein (LNAC, 1 mm), an NO
      scavenger, inhibited IKs enhancement. Application of an NO donor, sodium
      nitroprusside (SNP, 1 mm), enhanced IKs with a magnitude similar to that by a
      maximum dose (20 microm) of ginseonside Re, and subsequent application of
      ginsenoside Re failed to enhance IKs. Conversely, after IKs had been enhanced by
      ginsenoside Re (20 microm), subsequently applied SNP failed to further enhance
      IKs. 4 An inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ, 10 microm), barely suppressed IKs enhancement, while a thiol-alkylating
      reagent, N-ethylmaleimide (NEM, 0.5 mm), clearly suppressed it. A reducing
      reagent, di-thiothreitol (DTT, 5 mm), reversed both ginsenoside Re- and SNP
      induced IKs enhancement. 5 I(Ca,L) suppression by ginsenoside Re (3 microm) was
      abolished by SMT (1 microm) or LNAC (1 mm). NEM (0.5 mm) did not suppress I(Ca,L)
      inhibition and DTT (5 mm) did not reverse I(Ca,L) inhibition, whereas in the
      presence of ODQ (10 microm), ginsenoside Re (3 microm) failed to suppress
      I(Ca,L). 6 These results indicate that ginsenoside Re-induced IKs enhancement and
      I(Ca,L) suppression involve NO actions. Direct S-nitrosylation of channel protein
      appears to be the main mechanism for IKs enhancement, while a cGMP-dependent
      pathway is responsible for I(Ca,L) inhibition.

PMID- 15148248
TI  - Chronic NGF treatment of rat nociceptive DRG neurons in culture facilitates
      desensitization and deactivation of GABAA receptor-mediated currents.
AB  - 1 The present study tested the hypothesis that nerve growth factor (NGF) could
      affect presynaptic inhibition mediated by GABAA (GABA-sensitive ionotropic
      receptors) receptors on the afferents of nociceptive dorsal root ganglia (DRG)
      neurons, thus reducing the filtering of central nociceptive signals. 2 To
      investigate this issue, small-diameter, nociceptive DRG neurons were cultured for
      48-72 h either in the normal medium or in the presence of NGF (50 ng ml(-1)).
      After 15 min washout, cells were patch clamped with Cs+ containing electrodes to
      block GABAB (GABA-sensitive metabotropic receptors) receptor-activated currents.
      3 Chronically treated DRG neurons showed no difference in the peak amplitude of
      GABA-induced currents. However, NGF-treated cells exhibited increased fading of
      the response to continuous GABA application, with faster desensitization onset,
      decreased residual current at the end of agonist application and slower recovery
      from desensitization. Moreover, the deactivation phase after brief agonist pulses
      was also accelerated. 4 Unlike responses to GABA, chronic NGF treatment had no
      effect on the desensitization process to the excitatory transmitter ATP, as no
      difference in peak amplitude, fast and slow time constants of current decay was
      found. 5 Experimental tests indicated that the observed effects on GABA currents
      were not a reactive process triggered by washing out NGF after its long
      application. Acutely applied NGF did not change GABAA receptor-mediated
      responses. 6 NGF-treated neurons showed decreased sensitivity to the antagonist
      picrotoxin. The action of pentobarbitone, midazolam, bicuculline or gabazine was,
      however, unchanged. 7 These observations suggest that the modulation of GABAA
      receptor function of DRG nociceptors by NGF may contribute to the algogenic
      action of this neurotrophin.

PMID- 15148250
TI  - Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and
      conduit rat mesenteric arteries.
AB  - 1 In order to address mechanistic differences between arterial vessel types, we
      have compared the vasorelaxant actions of anandamide in resistance (G3) and
      conduit (G0) mesenteric arteries. 2 Anandamide produced concentration-dependent
      relaxations of pre-constricted G3 arteries with a maximal response that was
      significantly greater than seen in G0. 3 The CB1 receptor selective antagonists
      SR141716A (100 nm) and AM251 (100 nm) caused reductions in the vasorelaxant
      responses to anandamide in both arteries. Maximal vasorelaxant responses to
      anandamide were reduced in both arteries after treatment with capsaicin to
      deplete sensory neurotransmitters (10 microm for 1 h). 4 Vasorelaxation to
      anandamide was not affected by the nitric oxide synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME, 300 microm) in either artery. Only responses in G3
      arteries were sensitive to removal of the endothelium. In G3 vessels only,
      vasorelaxation to anandamide was reduced by inhibition of EDHF activity with a
      combination of charybdotoxin (100 nm) and apamin (500 nm) in the presence of L
      NAME (300 microm) and indomethacin (10 microm). 5 Antagonism of the novel
      endothelial cannabinoid receptor (O-1918, 1 microm) caused a reduction in the
      sensitivity to anandamide in G3 but not G0. 6 G3, but not G0, vessels showed a
      small reduction in vasorelaxant responses to anandamide after inhibition of gap
      junctional communication with 18alpha-GA (100 microm). 7 These results
      demonstrate that there are differences in the mechanisms of vasorelaxation to
      anandamide between conduit and resistance mesenteric arteries. In small
      resistance vessels, vasorelaxation occurs through stimulation of vanilloid
      receptors, CB1 receptors, and an endothelial receptor coupled to EDHF release. By
      contrast, in the larger mesenteric artery, vasorelaxation is almost entirely due
      to stimulation of vanilloid receptors and CB1 receptors, and is endothelium
      independent.

PMID- 15148249
TI  - A novel inhibitor of vacuolar ATPase, FR167356, which can discriminate between
      osteoclast vacuolar ATPase and lysosomal vacuolar ATPase.
AB  - 1 Vacuolar ATPase (V-ATPase) has been proposed as a drug target in lytic bone
      diseases. Studies of bafilomycin derivatives suggest that the key issue regarding
      the therapeutic usefulness of V-ATPase inhibitors is selective inhibition of
      osteoclast V-ATPase. Previous efforts to develop therapeutic inhibitors of
      osteoclast V-ATPase have been frustrated by a lack of synthetically tractable and
      biologically selective leads. Therefore, we tried to find novel potent and
      specific V-ATPase inhibitors, which have new structural features and inhibition
      selectivity, from random screening using osteoclast microsomes. Finally, a novel
      V-ATPase inhibitor, FR167356, was obtained through chemical modification of a
      parental hit compound. 2 FR167356 inhibited not only H+ transport activity of
      osteoclast V-ATPase but also H+ extrusion from cytoplasm of osteoclasts, which
      depends on the V-ATPase activity. As expected, FR167356 remarkably inhibited bone
      resorption in vitro. 3 FR167356 also showed inhibitory effects on other V
      ATPases, renal brush border V-ATPase, macrophage microsome V-ATPase and lysosomal
      V-ATPase. However, FR167356 was approximately seven-fold less potent in
      inhibiting lysosomal V-ATPase compared to osteoclast V-ATPase. Moreover, LDL
      metabolism in cells, which depends on acidification of lysosome, was blocked
      merely at higher concentration than bone resorption, suggesting that FR167356
      inhibits V-ATPase of osteoclast ruffled border membrane still more selectively
      than lysosome at the cellular level. 4 These results from the experiments seem to
      indicate that osteoclast V-ATPase may be different from lysosomal V-ATPase in
      respect of their structure. 5 FR167356 had a novel chemical structural feature as
      well as inhibitory characteristics distinctly different from any previously known
      V-ATPase inhibitor family. Therefore, FR167356 is thought to be a useful tool for
      estimating the essential characteristics of V-ATPase inhibitors for drug
      development.

PMID- 15148251
TI  - Identification of the active metabolite of ticlopidine from rat in vitro
      metabolites.
AB  - 1 Ticlopidine is a well-known anti-platelet agent, but is not active by itself in
      vitro. We identified a metabolite with anti-platelet activity, which was
      generated after incubation of 2-oxo-ticlopidine with phenobarbital-induced rat
      liver homogenate in vitro. 2 An active moiety (UR-4501) was isolated by high
      performance liquid chromatography after large-scale preparation of metabolites. 3
      The chemical structure of UR-4501 was determined by a combination of liquid
      chromatography mass/mass spectrometry (LC/MS/MS) and nuclear magnetic resonance
      (NMR) analysis. 4 UR-4501 produced a concentration-dependent inhibition (3-100
      microm) of ADP (10 microm)-induced human platelet aggregation, whereas 2-oxo
      ticlopidine (3-100 microm) did not elicit inhibitory responses. 5 UR-4501 (10-100
      microm) strongly inhibited ADP- and collagen-induced aggregation and slightly
      inhibited thrombin-induced aggregation. 6 The inhibition of rat washed platelet
      aggregation by UR-4501 (100 microm) persisted, even after the platelets had been
      washed twice. 7 These results suggest that UR-4501 is the molecule responsible
      for the in vivo activities of ticlopidine.

PMID- 15148252
TI  - The leaf extract of Ginkgo Biloba L. suppresses oxidized LDL-stimulated
      fibronectin production through an antioxidant action in rat mesangial cells.
AB  - 1 The leaf extract of Ginkgo Biloba L. exhibits a variety of pharmacological
      effects through an antioxidant action. We examined the effects of the leaf
      extract (Ginkgolon-24) on the production of fibronectin induced by oxidized low
      density lipoprotein (oxLDL) in rat mesangial cells. 2 Stimulation with oxLDL
      accelerated the production of fibronectin with the preceding generation of
      reactive oxygen species (ROS). Pretreatment with Ginkgolon-24 inhibited the oxLDL
      induced fibronectin production as well as ROS generation. 3 oxLDL also elicited
      the activation of SP-1, nuclear factor-kappaB, and cAMP response element-binding
      protein, which are transcription factors involved in the fibronectin production.
      Among these activated transcription factors, Ginkgolon-24 inhibited the
      activation of SP-1 only. 4 Furthermore, 7-ketocholesterol, an oxidized lipid in
      oxLDL particles, induced the production of fibronectin and the activation of SP
      1, which were also suppressed by Ginkgolon-24. 5 These results suggest that the
      leaf extract of Ginkgo Biloba L. inhibits the oxLDL-induced production of
      fibronectin probably through inhibitory effects on ROS generation and SP-1
      activation in rat mesangial cells.

PMID- 15148254
TI  - Experimental hypothyroidism modifies specific binding of A1 and A2A analogues to
      adenosine receptors in the rat kidney.
AB  - 1 Binding kinetic studies with the adenosine analogues [3H]CPA (0.250-50 nm) and
      [3H]CGS21680 (0.1-100 nm) were performed in renal tissue from control (NL) and
      thyroidectomised (HTX) rats. We propose that the low renal adenosine content
      reported in hypothyroid rats may induce changes in the density and/or affinity of
      adenosine receptor, distributed in the cortex (C), outer medulla (OM), and inner
      medulla (IM) of the kidney. 2 [3H]CPA and [3H]CGS21680 binding saturation
      isotherms were fitted by nonlinear regression analysis and evaluated by
      Furchgott's method. These results revealed high (KH) and low (KL) affinity (KD)
      sites for both compounds. As expected, a heterogeneous pattern was observed for
      Bmax and KD values. 3 Bound [3H]CPA and [3H]CGS21680 were displaced by increasing
      concentrations of nonlabelled DPCPX and NECA, respectively, indicating the
      presence of A1 and A2A adenosine receptors distributed in the renal segments
      studied. 4 The relative intrinsic efficacy (epsilon) for [3H]CPA and [3H]CGS21680
      showed extreme values (far from 1.0), 0.5 in IM NL and 2.70 in IM HTX for
      [3H]CGS21680. 5 Our results indicate that A2A adenosine receptor is predominant
      in IM from HTX, but A1 receptors are expressed preferentially in C in NL. 6 We
      conclude that the changes observed in number, affinity, and epsilon for the A2A
      receptor in IM from HTX might be responsible from alterations in medullary
      function, that is, incapacity for urine concentration as observed in the
      hypothyroid kidney.

PMID- 15148253
TI  - Effects of chronic treatment with escitalopram or citalopram on extracellular 5
      HT in the prefrontal cortex of rats: role of 5-HT1A receptors.
AB  - 1 Microdialysis was used to study the acute and chronic effects of escitalopram
      (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A
      receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor
      agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5
      hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. 2 Extracellular 5
      HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of
      0.15 and 0.63 mg kg(-1) ESCIT. No further increase was observed at 2.5 mg kg(-1)
      ESCIT (290%). 3 The effect of 13-day s.c. infusion of 10 mg kg(-1) day(-1) ESCIT
      on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of
      baseline), whereas exposure to ESCIT was similar. In contrast, the increase in
      extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%)
      was similar. However, brain and plasma levels of S-citalopram in rats infused
      with CIT for 13 days were lower than after 2 days. 4 Acute treatment with 2.5 mg
      kg(-1) ESCIT or 5 mg kg(-1) CIT raised extracellular 5-HT by 243 and 276%,
      respectively, in rats given chronic vehicle but had no effect in rats given ESCIT
      (10 mg kg(-1) day(-1)) or CIT (20 mg kg(-1) day(-1)) for 2 or 13 days, suggesting
      that the infused doses had maximally increased extracellular 5-HT. WAY100,635
      (0.1 mg kg(-1) s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of
      prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days,
      respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164%
      of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days,
      respectively. 5 8-OH-DPAT (0.025 mg kg(-1)) reduced extracellular 5-HT by 54% in
      control rats, but had no effect in those given ESCIT and CIT for 13 days. 6 This
      series of experiments led to the conclusion that chronic treatment with ESCIT
      desensitizes the 5-HT1A receptors, regulating the release of 5-HT in the
      prefrontal cortex and enhances the effect of the drug on extracellular 5-HT. They
      also indicate that chronic treatment with ESCIT and CIT did not prevent
      WAY100,635 from raising extracellular 5-HT.

PMID- 15148256
TI  - Ginseng saponins induce store-operated calcium entry in Xenopus oocytes.
AB  - 1 We investigated the effect of the active ingredients of Panax ginseng,
      ginsenosides, on store-operated Ca2+ entry (SOCE) using a two-electrode voltage
      clamp technique in Xenopus oocytes in which SOCE is monitored through Ca(2+)
      activated Cl- currents. 2 Under hyperpolarizing voltage clamp conditions,
      treatment with ginsenosides produced a biphasic Ca(2+)-activated Cl- current
      consisting of a rapid transient inward current and a slowly developing secondary
      sustained inward current. The transient inward current was inactivated rapidly,
      whereas the sustained inward current persisted for nearly 10 min. The effect of
      ginsenosides on the biphasic current was dose-dependent and reversible. The EC50
      was 42.8+/-11.6 and 46.6+/-7.1 microg ml(-1) for the transient and sustained
      inward current, respectively. 3 In the absence of extracellular Ca2+ ginsenosides
      induced only a transient inward current but in the presence of extracellular Ca2+
      ginsenosides induced the biphasic current. Magnitudes of the sustained currents
      were dependent on extracellular Ca2+ concentration. Sustained inward current
      induced by ginsenosides, but not transient inward current, and ginsenoside
      induced store-operated Ca2+ (SOC) currents (ISOC) were blocked by La3+, a Ca2+
      channel blocker, suggesting that the sustained inward current and ISOC was
      derived from an influx of extracellular Ca2+. 4 Treatment with 2-APB and heparin,
      which are IP3 receptor antagonists, inhibited the ginsenoside-induced biphasic
      current. Treatment with the PLC inhibitor, U73122, also inhibited the ginsenoside
      induced biphasic current. Intraoocyte injection of ATP-gammaS, but not adenylyl
      AMP-PCP, induced a persistent activation of ginsenoside-induced sustained current
      but did not affect the transient current. 5 In rat hippocampal neurons,
      ginsenosides inhibited both carbachol-stimulated intracellular Ca2+ release and
      intracellular Ca2+ depletion-activated SOCE. 6 These results indicate that
      ginsenoside might act as a differential regulator of intracellular Ca2+ levels in
      neurons and Xenopus oocytes.

PMID- 15148255
TI  - Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam,
      melatonin and galanin of human erythrocyte D-glucose transport.
AB  - 1 Nootropic drugs increase glucose uptake into anaesthetised brain and into
      Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a
      chemical structure similar to nootropics increases cerebellar uptake of glucose
      in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2
      oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH
      antagonise the inhibition of glucose transport by barbiturates, diazepam,
      melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. 2
      The potencies of nootropic drugs in opposing scopolamine-induced memory loss
      correlate with their potencies in antagonising pentobarbital inhibition of
      erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D
      levetiracetam and D-pyroglutamate, have higher antagonist Ki's against
      pentobarbital inhibition of glucose transport than more potent L-stereoisomers
      (P<0.001). 3 Piracetam and TRH have no direct effects on net glucose transport,
      but competitively antagonise hypnotic drug inhibition of glucose transport. Other
      nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital
      action, also inhibit glucose transport. Analeptics like bemigride and
      methamphetamine are more potent inhibitors of glucose transport than antagonists
      of hypnotic action on glucose transport. 4 There are similarities between amino
      acid sequences in human glucose transport protein isoform 1 (GLUT1) and the
      benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor
      subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the
      site of diazepam and piracetam interaction is a pocket outside the central
      hydrophilic pore region. 5 Nootropic pyrrolidone antagonism of hypnotic drug
      inhibition of glucose transport in vitro may be an analogue of TRH antagonism of
      galanin-induced narcosis.

PMID- 15148257
TI  - Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by
      the local anesthetic lidocaine.
AB  - 1 Voltage-gated Na+ channels are transmembrane proteins that are essential for
      the propagation of action potentials in excitable cells. Nav1.7 and Nav1.8 dorsal
      root ganglion Na+ channels exhibit different kinetics and sensitivities to
      tetrodotoxin (TTX). We investigated the properties of both channels in the
      presence of lidocaine, a local anesthetic (LA) and class I anti-arrhythmic drug.
      2 Nav1.7 and Nav1.8 Na+ channels were coexpressed with the beta1-subunit in
      Xenopus oocytes. Na+ currents were recorded using the two-microelectrode voltage
      clamp technique. 3 Dose-response curves for both channels had different EC50
      (dose producing 50% maximum current inhibition) (450 microm for Nav1.7 and 104
      microm for Nav1.8). Lidocaine enhanced current decrease in a frequency-dependent
      manner. Steady-state inactivation of both channels was also affected by
      lidocaine, Nav1.7 being the most sensitive. Only the steady-state activation of
      Nav1.8 was affected while the entry of both channels into slow inactivation was
      affected by lidocaine, Nav1.8 being affected to a larger degree. 4 Although the
      channels share homology at DIV S6, the LA binding site, they differ in their
      sensitivity to lidocaine. Recent studies suggest that other residues on DI and
      DII known to influence lidocaine binding may explain the differences in
      affinities between Nav1.7 and Nav1.8 Na+ channels. 5 Understanding the properties
      of these channels and their pharmacology is of critical importance to developing
      drugs and finding effective therapies to treat chronic pain.

PMID- 15148258
TI  - Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor
      amsacrine: mode of action.
AB  - 1 The topoisomerase II inhibitor amsacrine is used in the treatment of acute
      myelogenous leukemia. Although most anticancer drugs are believed not to cause
      acquired long QT syndrome (LQTS), concerns have been raised by reports of QT
      interval prolongation, ventricular fibrillation and death associated with
      amsacrine treatment. Since blockade of cardiac human ether-a-go-go-related gene
      (HERG) potassium currents is an important cause of acquired LQTS, we investigated
      the acute effects of amsacrine on cloned HERG channels to determine the
      electrophysiological basis for its proarrhythmic potential. 2 HERG channels were
      heterologously expressed in human HEK 293 cells and Xenopus laevis oocytes, and
      the respective potassium currents were recorded using patch-clamp and two
      microelectrode voltage-clamp electrophysiology. 3 Amsacrine blocked HERG currents
      in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner, with
      IC50 values of 209.4 nm and 2.0 microm, respectively. 4 HERG channels were
      primarily blocked in the open and inactivated states, and no additional voltage
      dependence was observed. Amsacrine caused a negative shift in the voltage
      dependence of both activation (-7.6 mV) and inactivation (-7.6 mV). HERG current
      block by amsacrine was not frequency dependent. 5 The S6 domain mutations Y652A
      and F656A attenuated (Y652A) or abolished (F656A, Y652A/F656A) HERG current
      blockade, indicating that amsacrine binding requires a common drug receptor
      within the pore-S6 region. 6 In conclusion, these data demonstrate that the
      anticancer drug amsacrine is an antagonist of cloned HERG potassium channels,
      providing a molecular mechanism for the previously reported QTc interval
      prolongation during clinical administration of amsacrine.

PMID- 15148259
TI  - NO and KATP channels underlie endotoxin-induced smooth muscle hyperpolarization
      in rat mesenteric resistance arteries.
AB  - 1 Smooth muscle membrane potential and tension measurements were made in isolated
      mesenteric resistance arteries from rats exposed to bacterial endotoxin
      (lipopolysaccharide, LPS; 10 mg kg(-1), i.p.) for 3 h to mimic septic shock
      syndrome. 2 Over this period, rats developed an endotoxaemic response, assessed
      in vivo as a 41+/-4 mmHg drop in mean blood pressure, vascular hyporeactivity to
      noradrenaline (1 microg kg(-1), i.v.) and a significant increase in core body
      temperature. 3 In mesenteric small resistance arteries from these rats (o.d. 180 
      240 microm), phenylephrine (0.01-3 microm)-evoked contraction was not altered
      when compared with arteries from sham-operated animals, but the concentration
      relaxation curve to acetylcholine (ACh; 0.01 - 3 microm) displayed a small, but
      significant, shift to the right. 4 The smooth muscle resting membrane potential (
      70.3+/-1.6 mV) in arteries from LPS-treated rats was significantly greater than
      in control arteries (-55.4+/-1.2 mV), but in both cases the smooth muscle was
      depolarized to a similar potential by the application of N(omega)-nitro-L
      arginine methyl ester (L-NAME; 0.3 mm; -54.1+/-2.3 vs -52.4+/-2.5 mV) or
      glibenclamide (10 microm; -55.0+/-2.1 vs -50.4+/-2.0 mV). 5 ACh (1 microm)
      elicited a maximal hyperpolarization, which ranged from -14.7+/-3.2 mV (in
      arteries from LPS-treated rats) to -20.6+/-2.4 mV (in arteries from sham-operated
      rats), and was not altered by the presence of L-NAME. Levcromakalim (1 microm)
      increased the smooth muscle membrane potential by around -24 mV in arteries from
      both sets of experimental animals. 6 These results indicate that at the level of
      the resistance vasculature, endotoxaemia is associated with pronounced smooth
      muscle hyperpolarization reflecting the action of NO on KATP channels. These
      changes were not associated with vascular hyporeactivity or depressed endothelial
      cell function in vitro, suggesting that mesenteric resistance arteries may not
      contribute to equivalent changes in vivo.

PMID- 15148260
TI  - Identification of a potent and highly efficacious, yet slowly desensitizing CB1
      cannabinoid receptor agonist.
AB  - 1 The relationship of agonist efficacy to the rate of G protein-coupled receptor
      signaling desensitization is controversial. 2 Expressing inwardly rectifying
      potassium channels (GIRKs) in Xenopus oocytes, we have devised a signaling assay
      that clearly identifies CB1 cannabinoid receptor agonists with low intrinsic
      efficacy. 3 In this assay, the synthetic CB1 agonists, AM411, AM782, AM1902,
      AM2233 and WIN55,212-2 and the endogenous cannabinoid, 2-arachidonoyl ester, were
      full agonists. 4 The synthetic CB1 agonist AM356 (methanandamide), the endogenous
      cannabinoids, anandamide and 2-arachidonoyl ether, and the phytocannabinoid,
      Delta9THC, were partial agonists. 5 The rate of desensitization of CB1 was
      independent of agonist efficacy. WIN55,212-2, AM782, AM1902, AM2233, and 2
      arachidonoyl glycerol ester all desensitized quickly, with desensitization rates
      varying from 14% min(-1) to 10% min(-1). AM356, AM411, anandamide, and Delta9THC
      all desensitized considerably slower, at a rate of 5% min(-1). 6 Despite high
      potency and efficacy, AM411 desensitized as slowly as anandamide and Delta9THC. 7
      CB1 agonist efficacy and rate of desensitization are not necessarily related.

PMID- 15148261
TI  - Investigation of the effects of P2 purinoceptor ligands on the micturition reflex
      in female urethane-anaesthetized rats.
AB  - 1 The effects of purinoceptor ligands for P2X1 and/or P2X3 receptors (alpha,beta
      meATP, IP(5)I, TNP-ATP, MRS 2179, PPADS, Phenol red and RO116-6446/008; i.v., n=4
      5) and for P2Y1 receptors (PPADS, MRS 2179 and MRS 2269; i.v., n=3-5) were
      investigated on the distension-evoked 'micturition reflex' in the urethane
      anaesthetized female rat. 2 Alpha,beta-meATP (180 nmol kg(-1) min(-1)), IP5I (10,
      30 and 100 nmol kg(-1)), TNP-ATP (1 micromol kg(-1)), MRS 2179 (1 micromol kg(
      1)) and PPADS (17 micromol kg(-1)) each caused maintained bladder contractions to
      occur during the infusion of saline into the bladder. PPADS (17 micromol kg(-1)
      min(-1)) had a similar effect when infused intravesicularly. Regular bladder
      contractions were not observed until the infusion of saline was halted. For IP5I,
      TNP-ATP, MRS 2179 and PPADS, the magnitude of postinfusion isovolumetric
      contractions was significantly reduced and, for IP5I, this action was also
      associated with a significant reduction in urethral relaxation. Additionally, TNP
      ATP caused a significant increase in the pressure and volume thresholds required
      to initiate a reflex. 3 Phenol red (a P2X1/P2X3 antagonist; 0.1 and 1 micromol
      kg(-1)) caused a significant increase in the pressure and volume thresholds
      required to initiate a reflex and, at the higher dose, also caused a reduction in
      postinfusion isovolumetric contractions. 4 RO116-6446/008 (a P2X1-selective
      antagonist; 1 and 10 micromol kg(-1)) only caused a reduction in postinfusion
      isovolumetric contractions. 5 It is concluded that P2X1 and P2X3 receptors play a
      fundamental role in the micturition reflex in urethane-anesthetized female rats.
      P2X3 receptor blockade raised the pressure and volume thresholds for the reflex,
      whereas P2X1 receptor blockade diminished motor activity associated with voiding.
      P2Y1 receptors may be involved in inhibition of rat detrusor tone.

PMID- 15148262
TI  - Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission
      in the rat isolated mesenteric arterial bed via a non-CB1/CB2 G(i/o) linked
      receptor.
AB  - 1 Noladin ether has recently been reported to be an endocannabinoid, with
      selectivity for the cannabinoid (CB) CB1 receptor. In the present study, we
      investigated the effects of noladin ether in the rat isolated mesenteric arterial
      bed, cultured dorsal root ganglia (DRG) cells and human vanilloid (TRPV1)
      receptor-expressing HEK293 cells (TRPV1-HEK293 cells). 2 Electrical field
      stimulation of the mesenteric bed evoked frequency-dependent vasorelaxation due
      to the action of calcitonin gene-related peptide (CGRP) released from sensory
      nerves. Noladin ether (0.1-3 microm) attenuated sensory neurogenic relaxation in
      a concentration-dependent manner. Noladin ether (1 microm) reduced vasorelaxation
      at a submaximal frequency (8 Hz), from 57.3+/-6.8 to 23.3+/-3.8% (P<0.05, n=4). 3
      The inhibitory effects of noladin ether were unaffected by the CB1 antagonists
      SR141716A and LY320135, and the CB2 antagonist SR144528 (1 microm). 4 Noladin
      ether had no effect on vasorelaxation elicited by exogenous CGRP or capsaicin.
      These data suggest that noladin ether is acting at a prejunctional site and no
      interaction with TRPV1 is involved. 5 In mesenteric beds from pertussis toxin
      (PTX)-pretreated rats, the inhibitory actions of noladin ether on sensory
      neurotransmission were abolished, indicating the involvement of G(i/o) protein
      coupled receptors. 6 Noladin ether evoked a concentration-dependent increase in
      intracellular Ca2+ concentration in TRPV1-HEK293 cells at 10 microm (36.5+/-3.2%
      of maximal capsaicin-induced response), but it was a less potent agonist than
      both capsaicin and anandamide and at 1 microm it was essentially inactive.
      Noladin ether (1 microm) had no effect on capsaicin-evoked Ca2+ responses in DRG
      cells, and produced no response alone, indicating it neither modulates nor acts
      directly on TRPV1 receptors. 7 These data demonstrate that noladin ether
      attenuates sensory neurotransmission in rat mesenteric arteries via a non-CB1 non
      CB2 PTX-sensitive prejunctional site, independently of TRPV1 receptors.

PMID- 15148263
TI  - Influence of sodium substitutes on 5-HT-mediated effects at mouse 5-HT3
      receptors.
AB  - 1 The influence of sodium ion substitutes on the 5-hydroxytryptamine (5-HT)
      induced flux of the organic cation [14C]guanidinium through the ion channel of
      the mouse 5-HT3 receptor and on the competition of 5-HT with the selective 5-HT3
      receptor antagonist [3H]GR 65630 was studied, unless stated otherwise, in mouse
      neuroblastoma N1E-115 cells. 2 Under physiological conditions (135 mm sodium), 5
      HT induced a concentration-dependent [14C]guanidinium influx with an EC50 (1.3
      microm) similar to that in electrophysiological studies. 3 The stepwise
      replacement of sodium by increasing concentrations of the organic cation
      hydroxyethyl trimethylammonium (choline) concentration dependently caused both a
      rightward shift of the 5-HT concentration-response curve and an increase in the
      maximum effect of 5-HT. Complete replacement of sodium resulted in a 34-fold
      lower potency of 5-HT and an almost two times higher maximal response. A low
      potency of 5-HT in choline buffer was also observed in other 5-HT3 receptor
      expressing rodent cell lines (NG 108-15 or NCB 20). 4 Replacement of Na+ by Li+
      left the potency and maximal effects of 5-HT almost unchanged. Replacement by
      tris (hydroxymethyl) methylamine (Tris), tetramethylammonium (TMA) or N-methyl-d
      glucamine (NMDG) caused an increase in maximal response to 5-HT similar to that
      caused by choline. The potency of 5-HT was only slightly reduced by Tris, to a
      high degree decreased by TMA (comparable to the decrease by choline), but not
      influenced by NMDG. 5 The potency of 5-HT in inhibiting [3H]GR65630 binding to
      intact cells was 35-fold lower when sodium was completely replaced by choline,
      but remained unchanged after replacement by NMDG. 6 The results are compatible
      with the suggestion that choline competes with 5-HT for the 5-HT3 receptor; the
      increase in maximal response may be partly due to a choline-mediated delay of the
      5-HT-induced desensitization. For studies of 5-HT-evoked [14C]guanidinium flux
      through 5-HT3 receptor channels, NMDG appears to be an 'ideal' sodium substituent
      since it increases the signal-to-noise ratio without interfering with 5-HT
      binding.

PMID- 15148265
TI  - Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit
      cardiomyocytes.
AB  - 1 We examined whether edaravone (Eda), a clinically available radical scavenger,
      directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and
      whether the timing of its application is critical for protection. 2
      Cardioprotective effects of edaravone were tested in the modified cell-pelleting
      model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2)
      in isolated adult rabbit ventricular cells. Cell death and reactive oxygen
      species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA,
      respectively. These parameters were evaluated objectively using flow cytometory.
      3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/
      1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied
      either throughout the entire experiment (Through) or only at reoxygenation
      (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control)
      and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone
      was applied 10 min after reoxygenation, its protective effect disappeared.
      Cardioprotection by edaravone was more remarkable than that afforded by other
      free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There
      is a positive correlation between the cardioprotective effect of edaravone and
      the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in
      electrical properties, and significantly prolonged the time to contracture
      induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone
      directly protects cardiomyocytes from I/R injury by attenuating ROS production,
      even when applied at the time of reoxygenation, suggesting that edaravone could
      be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation
      injury.

PMID- 15148264
TI  - Functional M3 muscarinic acetylcholine receptors in mammalian hearts.
AB  - In contrast to most peripheral tissues where multiple subtypes of muscarinic
      acetylcholine receptor (mAChR) coexist, with each of them playing its part in the
      orchestra of parasympathetic innervation, the myocardium has been traditionally
      considered to possess a single mAChR subtype. Although there is much evidence to
      support the notion that one receptor subtype (M2) orchestrates myocardial
      muscarinic transduction, there is emerging evidence that M1 and M3 receptors are
      also expressed and are of potential physiological, pathophysiological and
      pharmacological relevance. Clarifying this issue has a profound impact on our
      thinking about the cholinergic control of the heart function and disease and
      approaches to new drug development for the treatment of heart disease associated
      with parasympathetic dysfunction. This review article presents evidence for the
      presence of the M3 receptor subtype in the heart, and analyzes the controversial
      data from published pharmacological, functional and molecular studies. The
      potential roles of the M3 receptors, in parasympathetic control of heart function
      under normal physiological conditions and in heart failure, myocardial ischemia
      and arrhythmias, are discussed. On the basis of these considerations, we have
      made some proposals concerning the future of myocardial M3 receptor research.

PMID- 15148266
TI  - Effect of adrenalectomy and corticosterone replacement on prepulse inhibition and
      locomotor activity in mice.
AB  - 1 Stress is a risk factor in psychiatric illnesses such as schizophrenia. The aim
      of the present study was to investigate the effect of different circulating
      levels of the adrenal steroid corticosterone (CORT) on locomotor hyperactivity
      and prepulse inhibition of acoustic startle, two behavioural animal models of
      aspects of schizophrenia. 2 Male C57BL/6J mice (n=10 per group) were
      anaesthetised with isoflurane and sham-operated or adrenalectomised (ADX). ADX
      mice were implanted with 50 mg pellets consisting of 100% cholesterol, or 2, 10
      or 50 mg of CORT mixed with cholesterol. CORT pellet implantation dose
      dependently increased plasma CORT levels 3 weeks after surgery. Starting 1 week
      after surgery, mice were tested for prepulse inhibition after injection of saline
      or 5 mg kg(-1) of haloperidol. 3 In intact mice and in mice implanted with 10 mg
      of CORT, haloperidol treatment significantly increased prepulse inhibition
      (average values from 38 - 42 to 52%). Similar results were observed when testing
      the mice for amphetamine-induced locomotor hyperactivity (5 mg kg(-1)). In
      contrast, there was no significant effect of haloperidol in mice implanted either
      with cholesterol or 2 or 50 mg of CORT. 4 These results in behavioural animal
      models of schizophrenia suggest an important role of the stress hormone CORT in
      modulating dopaminergic activity in this illness.

PMID- 15148267
TI  - Electrical and mechanical components of dyssynchrony in heart failure patients
      with normal QRS duration and left bundle-branch block: impact of left and
      biventricular pacing.
AB  - BACKGROUND: Resynchronization pacing is an effective symptomatic treatment for
      heart failure patients with prolongation of the QRS duration (QRSd).
      Dyssynchronous contraction of the left ventricle is also observed with normal
      QRSd. We set out to determine how electrical activation of the left ventricular
      (LV) free wall differed between patients with left bundle-branch block (LBBB) and
      normal QRSd and if synchrony improved during pacing in patients with normal QRSd.
      METHODS AND RESULTS: Twenty-two patients were implanted with resynchronization
      pacemakers, 13 with LBBB (mean QRS, 171 ms) and 9 with normal QRSd <120 ms (mean,
      100 ms). LV lead electrograms and surface ECGs in sinus rhythm (unpaced) were
      recorded. Conventional and tissue Doppler echocardiography were performed without
      pacing, with LV and biventricular pacing at optimal atrioventricular delay. Lead
      electrograms from the LV free wall were later in the LBBB patients in absolute
      terms (155 ms [SD 23] versus 65.5 ms [SD 25]; P=0.05) and also relative to the
      surface QRS (90.5% [SD 8] versus 65.5% [SD 24]). Improved synchrony of the left
      and right ventricles (interventricular synchrony) and of the LV myocardial
      segments (intraventricular synchrony) was observed for patients with LBBB and
      normal QRSd. Baseline LV synchrony correlated with timing of LV free-wall
      electrical activation. Improved intraventricular synchrony during pacing also
      correlated with LV free-wall electrical activation time. CONCLUSIONS:
      Resynchronization of systole can be achieved for patients with normal QRSd and
      LBBB during biventricular and LV pacing. The timing of LV free-wall electrical
      activation correlated with the improvement in synchrony.

PMID- 15148268
TI  - Beta-adrenoceptor blocker carvedilol provides cardioprotection via an adenosine
      dependent mechanism in ischemic canine hearts.
AB  - BACKGROUND: Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action
      that is more effective for the treatment of congestive heart failure than other
      beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress,
      which may consequently reduce the deactivation of adenosine-producing enzymes and
      increase cardiac adenosine levels. Therefore, carvedilol may also have a
      protective effect on ischemia and reperfusion injury, because adenosine mediates
      cardioprotection in ischemic hearts. METHODS AND RESULTS: In anesthetized dogs,
      the left anterior descending coronary artery was occluded for 90 minutes,
      followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0+/
      2.8% versus 40.9+/-4.2% in controls), and this effect was completely reversed by
      the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2+/
      5.4%) or by an inhibitor of ecto-5'-nucleotidase (44.4+/-3.6%). There were no
      differences of either area at risk or collateral flow among the various groups.
      When the coronary perfusion pressure was reduced in other dogs so that coronary
      blood flow was decreased to 50% of the nonischemic level, carvedilol increased
      coronary blood flow (49.4+/-5.6 to 73.5+/-7.5 mL x 100 g(-1) x min(-1); P<0.05)
      and adenosine release (112.3+/-22.2 to 240.6+/-57.1 nmol/L; P<0.05) during
      coronary hypoperfusion. This increase of coronary blood flow was attenuated by
      either 8-sulfophenyltheophylline or superoxide dismutase. In human umbilical vein
      endothelial cells cultured with or without xanthine and xanthine oxidase,
      carvedilol caused an increase of ecto-5'-nucleotidase activity. CONCLUSIONS:
      Carvedilol shows a cardioprotective effect against ischemia and/or reperfusion
      injury via adenosine-dependent mechanisms.

PMID- 15148269
TI  - Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in
      hypertensive patients.
AB  - BACKGROUND: The pathogenesis of essential hypertension in blacks may differ from
      that in whites. In particular, black patients usually present with a salt
      sensitive, low-renin form, which in animal models is associated with enhanced
      activity of endothelin-1 (ET-1). This study aimed to assess whether ethnic
      differences exist in the vascular activity of ET-1 in normotensive and
      hypertensive blacks and whites. METHODS AND RESULTS: Forearm blood flow (FBF)
      responses to intraarterial infusion of an ET(A) receptor blocker (BQ-123) were
      analyzed by plethysmography in 37 normotensive patients and 27 hypertensive
      patients according to race. BQ-123 did not affect FBF in normotensive subjects
      (P=0.30), whereas it produced significant vasodilation in hypertensive subjects
      (P<0.001). In normotensives, FBF response to BQ-123 was similar in white (n =22)
      and black (n =15) patients (P=0.85). In contrast, in hypertensive patients, the
      vasodilator effect of ET(A) receptor blockade was significantly higher in blacks
      (n =13) than in whites (n =14) (P=0.01). To rule out differences in smooth muscle
      reactivity, the effects of race on FBF responses to exogenous ET-1 were analyzed
      in the hypertensive subgroups. Endothelin-1 induced a significant
      vasoconstriction in both white (n =7) and black patients (n =5) (both P<0.001),
      without differences between them (P=0.46). In 8 black hypertensives, the response
      to selective ET(A) blockade was not modified by nonselective blockade of ET-1
      receptors by co-infusion of BQ-123 and BQ-788 (P=0.66). CONCLUSIONS: Hypertensive
      blacks have enhanced ET(A)-dependent vasoconstrictor tone, probably related to
      increased production of ET-1. Given the negative vascular effects of ET-1, this
      abnormality may contribute to the pathogenesis of hypertension and its
      complications in black patients.

PMID- 15148270
TI  - In vivo induction of endothelial apoptosis leads to vessel thrombosis and
      endothelial denudation: a clue to the understanding of the mechanisms of
      thrombotic plaque erosion.
AB  - BACKGROUND: The mechanisms of thrombosis on plaque erosion are poorly understood.
      We examined the potential role of endothelial apoptosis in endothelial erosion
      and vessel thrombosis. METHODS AND RESULTS: Segments of New Zealand White rabbit
      femoral arteries were temporarily isolated in vivo. One artery was incubated with
      staurosporin for 30 minutes, whereas the contralateral artery was incubated with
      saline and served as control. Three days later, thrombosis was evaluated
      angiographically and histologically. TUNEL score in the endothelial layer was
      significantly increased in staurosporin-treated arteries compared with controls
      (2.43+/-0.30 versus 0.93+/-0.44, respectively; P=0.001). Large areas of
      endothelial denudation were detectable in staurosporin-treated vessels, whereas
      endothelium integrity was almost preserved in the saline group. Vessel thrombosis
      occurred in 58% of staurosporin-treated arteries (7 of 12) but in only 8% of
      saline-treated segments (P<0.01). Immunoreactivities for tissue factor,
      platelets, and fibrin were detectable within the thrombus. Addition of ZVAD-fmk
      (0.1 mmol/L) significantly reduced the occurrence of thrombosis (1 of 7 arteries
      or 14%, P=0.04). These results were confirmed in balloon-injured atheromatous
      arteries. CONCLUSIONS: In vivo induction of endothelial apoptosis leads to both
      vessel thrombosis and endothelial denudation. Endothelial apoptosis may be a
      critical step in the transition from a stable endothelialized plaque to plaque
      erosion and thrombosis.

PMID- 15148271
TI  - Double-blind, randomized controlled trial on the effect of leukocyte-depleted
      erythrocyte transfusions in cardiac valve surgery.
AB  - BACKGROUND: Leukocytes in allogeneic blood transfusions are believed to be the
      cause of immunomodulatory events. A few trials on leukocyte removal from
      transfusions in cardiac surgery have been conducted, and they showed inconclusive
      results. We found in a previous study a decrease in mortality rates and number of
      infections in a subgroup of more heavily transfused patients. METHODS AND
      RESULTS: Patients (n=496) undergoing valve surgery (with or without CABG) were
      randomly assigned in a double-blind fashion to receive standard buffy coat
      depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD).
      The primary end point was mortality at 90 days, and secondary end points were in
      hospital mortality, multiple organ dysfunction syndrome, infections, intensive
      care unit stay, and hospital stay. The difference in mortality at 90 days was not
      significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence
      interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as
      high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99
      to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was
      similar, although more patients with multiple organ dysfunction syndrome died in
      the PC group. LD was associated with a significantly reduced infection rate (PC
      31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive
      care unit stay and hospital stay were similar, and postoperative complications
      increased with the number of transfused units. CONCLUSIONS: Mortality at 90 days
      was not significantly different; however, a beneficial effect of LD in valve
      surgery was found for the secondary end points of in-hospital mortality and
      infections.

PMID- 15148273
TI  - Clinical correlates and prognostic significance of exercise-induced ventricular
      premature beats in the community: the Framingham Heart Study.
AB  - BACKGROUND: Recent investigations suggest that ventricular premature beats during
      exercise (EVPBs) are associated with increased cardiovascular mortality in
      asymptomatic individuals, but mechanisms underlying the association are unclear.
      METHOD AND RESULTS: We evaluated 2885 Framingham Offspring Study participants
      (1397 men; mean age, 43 years) who were free of cardiovascular disease and who
      underwent a routine exercise stress test; 792 participants (27%) had development
      of EVPBs (median, 0.22/min of exercise). Logistic regression was used to evaluate
      predictors of EVPBs. Cox models were used to examine the relations of infrequent
      (less than or equal to median) and frequent (greater than median) versus no EVPBs
      to incidence of hard coronary heart disease (CHD) event (recognized myocardial
      infarction, coronary insufficiency, or CHD death) and all-cause mortality,
      adjusting for vascular risk factors and exercise variables. Age and male sex were
      key correlates of EVPBs. During follow-up (mean, 15 years), 142 (113 men) had a
      first hard CHD event and 171 participants (109 men) died. EVPBs were not
      associated with hard CHD events but were associated with increased all-cause
      mortality rates (multivariable-adjusted hazards ratio, 1.86, 95% CI, 1.24 to 2.79
      for infrequent, and 1.71, 95% CI, 1.18 to 2.49 for frequent EVPBs versus none).
      The relations of EVPBs to mortality risk were not influenced by VPB grade,
      presence of recovery VPBs, left ventricular dysfunction, or an ischemic ST
      segment response. CONCLUSIONS: In our large, community-based sample of
      asymptomatic individuals, EVPBs were associated with increased risk of death at a
      much lower threshold than previously reported. Additional studies are needed to
      confirm these findings and to clarify the underlying mechanisms.

PMID- 15148272
TI  - Heparin cofactor II is a novel protective factor against carotid atherosclerosis
      in elderly individuals.
AB  - BACKGROUND: Thrombin plays a crucial role in atherothrombotic changes. Because
      heparin cofactor II (HCII) inhibits thrombin actions after binding to dermatan
      sulfate at injured arterial walls, HCII may negatively regulate thrombin actions
      in vascular walls. We hypothesized that plasma HCII activity is a preventive
      factor against atherosclerotic changes, especially in elderly individuals who
      already have atherosclerotic vascular injuries. METHODS AND RESULTS: Maximum
      plaque thickness (MPT) in the carotid artery was measured by ultrasonography in
      306 Japanese elderly individuals (154 men and 152 women; age, 40 to 91 years;
      68.9+/-11.1 years, mean+/-SD). The relevance of cardiovascular risk factors
      including plasma HCII activity to the severity of MPT was statistically
      evaluated. Plasma HCII activity decreased with age. Simple linear regression
      analysis after adjustments for age and sex showed that lipoprotein(a),
      glycosylated hemoglobin A1c, and presence of diabetes mellitus significantly
      contributed to an increase in MPT values (r=0.119, P<0.05; r=0.196, P<0.001; and
      r=0.227, P<0.0001, respectively). In contrast, high-density lipoprotein (HDL)
      cholesterol and HCII activity were negatively correlated with MPT values (r=
      0.117, P<0.05, and r=-0.202, P<0.0005, respectively). Multiple regression
      analysis revealed that plasma HCII activity and HDL cholesterol independently
      contributed to the suppression of MPT values and that the antiatherogenic
      contribution of HCII activity was stronger than that of HDL cholesterol (P<0.001
      and P<0.05, respectively). CONCLUSIONS: These results suggest that HCII can be a
      novel and independent antiatherogenic factor. Moreover, HCII is a stronger
      predictive factor than HDL cholesterol against carotid atherosclerosis in elderly
      individuals.

PMID- 15148274
TI  - Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase
      marker in acute myocardial infarction.
AB  - BACKGROUND: The delayed release of serum cardiac markers such as creatine kinase
      isoenzyme MB and equivocal early electrocardiographic changes have hampered a
      diagnosis of acute myocardial infarction (AMI) in the early phase after its
      onset. Therefore, a reliable serum biochemical marker for the diagnosis of AMI in
      the very early phase is desirable. METHODS AND RESULTS: Serum samples were
      collected from the patients with AMI, unstable angina pectoris, stable angina
      pectoris, and other diseases. Levels of serum deoxyribonuclease I (DNase I)
      activity in the patients were determined. An abrupt elevation of serum DNase I
      activity was observed within approximately 3 hours of the onset of symptoms in
      patients with AMI, with significantly higher activity levels (21.7+/-5.10 U/L) in
      this group compared with the other groups with unstable angina pectoris (10.4+/
      4.41 U/L), angina pectoris (10.8+/-3.70 U/L), and other diseases (9.22+/-4.16
      U/L). Levels of the DNase I activity in serum then exhibited a marked time
      dependent decline within 12 hours and had returned to basal levels within 24
      hours. CONCLUSIONS: We suggest that serum DNase I activity could be used as a new
      diagnostic marker for the early detection of AMI.

PMID- 15148275
TI  - Gene transfer of stromal cell-derived factor-1alpha enhances ischemic
      vasculogenesis and angiogenesis via vascular endothelial growth
      factor/endothelial nitric oxide synthase-related pathway: next-generation
      chemokine therapy for therapeutic neovascularization.
AB  - BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) is implicated as a
      chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that
      SDF-1alpha gene transfer would induce therapeutic neovascularization in vivo by
      functioning as a chemokine of EPC. METHODS AND RESULTS: To examine SDF-1alpha
      induced mobilization of EPC, we used bone marrow-transplanted mice whose blood
      cells ubiquitously express beta-galactosidase (LacZ). We produced unilateral
      hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF
      1alpha or empty plasmids into the ischemic muscles. SDF-1alpha gene transfer
      mobilized EPCs into the peripheral blood, augmented recovery of blood perfusion
      to the ischemic limb, and increased capillary density associated with partial
      incorporation of LacZ-positive cells into the capillaries of the ischemic limb,
      suggesting that SDF-1alpha induced vasculogenesis and angiogenesis. SDF-1alpha
      gene transfer did not affect ischemia-induced expression of vascular endothelial
      growth factor (VEGF) but did enhance Akt and endothelial nitric oxide synthase
      (eNOS) activity. Blockade of VEGF or NOS prevented all such SDF-1alpha-induced
      effects. CONCLUSIONS: SDF-1alpha gene transfer enhanced ischemia-induced
      vasculogenesis and angiogenesis in vivo through a VEGF/eNOS-related pathway. This
      strategy might become a novel chemokine therapy for next generation therapeutic
      neovascularization.

PMID- 15148276
TI  - Arginine vasopressin levels are elevated and correlate with functional status in
      infants and children with congestive heart failure.
AB  - BACKGROUND: Arginine vasopressin (AVP) is a vasoactive hormone that acts on the
      kidney to conserve solute-free water and produces a potent vasoconstrictive
      effect during hypovolemic states. AVP levels are elevated in adults with
      congestive heart failure (CHF), and early clinical trials using AVP antagonists
      are being conducted. The purpose of this study was to determine if AVP levels (1)
      are elevated in children with CHF attributable to left ventricular dysfunction or
      pulmonary overcirculation attributable to large left-to-right shunts and (2) can
      predict functional clinical status. METHODS AND RESULTS: AVP levels were measured
      in patients with dilated cardiomyopathy (DCM) and CHF and in patients with large
      left-to-right intracardiac shunts. Each patient with DCM (ejection fraction
      percent <40%) was classified as NYHA functional class I through IV when the AVP
      level was drawn. Serum sodium was measured, serum osmolality was calculated, and
      echocardiograms and chest radiographs were performed on all study patients. AVP
      levels were also measured in age-matched controls. Mean AVP level in children
      with DCM (n=27) was 10.3 pg/mL (+/-12.8) versus 3.7 pg/mL (+/-2.4) in controls
      (n=15) (P<0.01). Mean AVP level in children with left-to-right shunts (n=14) was
      13.9 pg/mL (+/-17.3) versus 3.5 pg/mL (+/-1.3) in controls (n=8) (P<0.04). In
      patients with DCM, AVP levels correlated directly with NYHA functional class
      (r2=0.73, P<0.001). CONCLUSIONS: Arginine vasopressin levels are elevated in
      infants and children with CHF attributable to left ventricular dysfunction and in
      infants with large left-to-right intracardiac shunts. Furthermore, there is a
      direct relationship between AVP level and the severity of heart failure in
      patients with DCM.

PMID- 15148277
TI  - Prognostic value of troponin I in cardiac risk stratification of cancer patients
      undergoing high-dose chemotherapy.
AB  - BACKGROUND: In patients with aggressive malignancies who are undergoing high-dose
      chemotherapy, even minimal elevation of troponin I (TnI) is associated with late
      left ventricular dysfunction. The time course of the subclinical myocardial
      damage and its impact on the clinical outcome have never been investigated
      previously. METHODS AND RESULTS: In 703 cancer patients, we measured TnI soon
      after chemotherapy (early TnI) and 1 month later (late TnI). Troponin was
      considered positive for values > or =0.08 ng/mL. Clinical and left ventricular
      ejection fraction evaluation (echocardiography) were performed before
      chemotherapy, 1, 3, 6, and 12 months after the end of the treatment, and again
      every 6 months afterward. Three different TnI patterns were identified, and
      patients were grouped accordingly. In 495 patients, both early and late TnI
      values were <0.08 ng/mL (TnI-/- group); in 145, there was only an early increase
      (TnI+/- group); and in 63 patients, both values increased (TnI+/+ group). In the
      TnI-/- group, no significant reduction in ejection fraction was observed during
      the follow-up, and there was a very low incidence of cardiac events (1%). In
      contrast, a greater incidence of cardiac events occurred in TnI-positive
      patients, particularly in the TnI(+/+) group (84% versus 37% in the TnI+/- group;
      P<0.001). CONCLUSIONS: TnI release pattern after high-dose chemotherapy
      identifies patients at different risks of cardiac events in the 3 years
      thereafter. This stratification allows us to differentiate the monitoring program
      and to plan, in selected patients, preventive strategies aimed at improving
      clinical outcome.

PMID- 15148278
TI  - Right ventricular enlargement on chest computed tomography: prognostic role in
      acute pulmonary embolism.
AB  - BACKGROUND: We investigated the prognostic role of right ventricular enlargement
      on multidetector-row chest CT in acute pulmonary embolism (PE). METHODS AND
      RESULTS: We studied 63 patients with CT-confirmed PE who underwent
      echocardiography within the ensuing 24 hours. Adverse clinical events, defined as
      30-day mortality or the need for cardiopulmonary resuscitation, mechanical
      ventilation, pressors, rescue thrombolysis, or surgical embolectomy, were present
      in 24 patients. We performed off-line CT measurements of right and left
      ventricular dimensions (RV(D), LV(D)) with axial and 2-dimensional reconstructed
      4-chamber (4-CH) views. The proportion of patients with RV(D)/LV(D)>0.9 on the
      axial view was similar in patients with (70.8%) and those without adverse events
      (71.8%; P=0.577). In contrast, RV(D)/LV(D)>0.9 on the 4-CH view was more common
      in patients with (80.3%) than without (51.3%; P=0.015) adverse events. The area
      under the curve of RV(D)/LV(D) from the axial and 4-CH views for predicting
      adverse events was 0.667 and 0.753, respectively. Sensitivity and specificity of
      RV(D)/LV(D)>0.9 for predicting adverse events were 37.5% and 92.3% on the axial
      view and 83.3% and 48.7% on the reconstructed 4-CH view, respectively.
      RV(D)/LV(D)>0.9 on the 4-CH view was an independent predictor for adverse events
      (OR, 4.02; 95% CI, 1.06 to 15.19; P=0.041) when adjusted for age, obesity,
      cancer, and recent surgery. CONCLUSIONS: Right ventricular enlargement on the
      reconstructed CT 4-CH views predicts adverse clinical events in patients with
      acute PE. Ventricular CT measurements obtained from 4-CH views are superior to
      those from axial views for identifying high-risk patients.

PMID- 15148280
TI  - Prognostic value of pharmacological stress echocardiography is affected by
      concomitant antiischemic therapy at the time of testing.
AB  - BACKGROUND: The aim of this study was to determine whether antianginal
      medications affect the prognostic value of pharmacological stress
      echocardiography. METHODS AND RESULTS: From the EPIC-EDIC Data Bank, 7333
      patients (5452 men; age; 59+/-10 years) underwent pharmacological stress
      echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 minutes;
      n=4984) or high-dose dobutamine (up to 40 microg x kg(-1) x min(-1); n=2349)
      (DET) for diagnostic purposes. At the time of testing, 1791 patients were on
      antiischemic therapy (nitrates and/or calcium antagonists and/or beta-blockers).
      Patients were followed up for a mean of 2.6 years (range, 1 to 206 months). DET
      was positive for myocardial ischemia in 2854 patients (39%) and negative in 4479
      (61%). Total mortality was 336 (4.5%). Death was attributed to cardiac causes in
      161 patients (2.1%). Survival was highest in patients with negative DET off
      therapy and lowest in patients with positive DET studied on therapy (95% versus
      81%; P=0.0000). Survival was comparable in patients with a negative test on
      therapy and in patients with a positive test off therapy (88% versus 84%, P=NS).
      CONCLUSIONS: Ongoing antiischemic therapy at the time of testing heavily
      modulates the prognostic value of pharmacological stress echo. In the presence of
      concomitant antiischemic therapy, a positive test is more prognostically
      malignant, and a negative test less prognostically benign.

PMID- 15148281
TI  - Intraprocedural stent thrombosis during implantation of sirolimus-eluting stents.
AB  - BACKGROUND: Intraprocedural stent thrombosis (IPST) is a rare event (<0.01% in
      our experience with bare metal stents), with the exception of specific settings
      such as acute myocardial infarction, thrombus-containing lesions, and
      dissections. We report the occurrence of this event during elective implantation
      of sirolimus-eluting stents. METHODS AND RESULTS: Between April 2002 and August
      2003, 670 patients with 1362 lesions were treated with Cypher (Cordis, Johnson
      and Johnson Co) sirolimus-eluting stent implantation in San Raffaele Hospital and
      EMO Centro Cuore Columbus. Diabetes mellitus was present in 142 patients (21%),
      and 164 (24.5%) had unstable angina. Pretreatment with glycoprotein IIb/IIIa (GP
      IIb/IIIa) inhibitors was carried out in 235 patients (35%). Total stent length
      per vessel was 42.9+/-28.3 mm. IPST occurred in 5 patients (0.7%). None of the
      patients with IPST were pretreated with GP IIb/IIIa inhibitors. Using univariate
      exact logistic regression, only total stent length per vessel, in millimeters
      (exact OR, 1.03; 95% CI, 1.011 to 1.046; P=0.0028), was associated with the
      occurrence of IPST. CONCLUSIONS: Stent length was associated with the occurrence
      of IPST. Particular attention will need to be directed to this potential
      complication when long sirolimus-eluting stents are being used.

PMID- 15148282
TI  - The James B. Herrick Award Lecture. 2003. Clinical research: whose agenda is it?

PMID- 15148279
TI  - Post-sirolimus-eluting stent restenosis treated with repeat percutaneous
      intervention: late angiographic and clinical outcomes.
AB  - BACKGROUND: We evaluated the clinical and angiographic outcomes of patients
      presenting with restenosis after sirolimus-eluting stent (SES) implantation
      treated with repeated percutaneous intervention. METHODS AND RESULTS: A total of
      24 consecutive patients have undergone repeated percutaneous intervention to
      treat post-SES restenosis (27 lesions). The restenosis was located within the
      stent in 93% of lesions. From the 27 lesions, 1 (4%) was re-treated with a bare
      stent, 3 (11%) were treated with balloon dilatation, and the remaining 23 lesions
      (85%) were treated with repeated drug-eluting stent implantation (SES in 12
      lesions [44%], paclitaxel-eluting stents in 11 lesions [41%]). The event-free
      survival rate was 70.8% after a median follow-up of 279 days from the post-SES
      treatment. The overall recurrent restenosis rate was 42.9%. The risk of recurrent
      restenosis was increased for patients with hypercholesterolemia, previous
      angioplasty, failed brachytherapy, post-SES restenosis needing early (<6 months)
      treatment, and post-SES restenosis treated with balloon dilatation. The recurrent
      restenosis rate of originally de novo lesions re-treated with drug-eluting stents
      was 18.2%. CONCLUSIONS: Even though de novo lesions treated with SES at baseline
      and re-treated with drug-eluting stents had reasonably better outcomes than other
      lesion types and strategies, our study shows that the treatment of post-SES
      restenosis is currently suboptimal and warrants further investigation.

PMID- 15148284
TI  - Images in cardiovascular medicine. Isolated subsegmental pulmonary embolus
      diagnosed by multidetector-row computed tomography.

PMID- 15148283
TI  - Images in cardiovascular medicine. Double aortic arch.

PMID- 15148285
TI  - Surgery may be better than PCI in patients with multivessel disease at high risk.

PMID- 15148286
TI  - Generation and selection of an IgG-driven autoimmune repertoire during B
      lymphopoiesis in Igmicro-deficient/lpr mice.
AB  - Class switch recombination (CSR) is a well-regulated process that occurs in
      peripheral lymphoid tissue, and is thought of as an important factor constructing
      the memory repertoire. We have recently shown that CSR normally occurs during
      bone marrow (BM) development, and these isotype-switched B cells are negatively
      selected by Fas signaling. This novel pathway of B cell development may generate
      a primary repertoire driven by gamma-heavy receptors, the nature of which is yet
      unknown. To study this gammaH-driven repertoire we used mice lacking IgM
      transmembrane tail exon ( micro MT), where B cell development is limited by their
      ability to undergo CSR. We already showed that lack of Fas signaling rescues
      development of a significant population of isotype-switched B cells and
      production of high titers of non-IgM serum antibodies in micro MT mice deficient
      in Fas ( micro MT/lpr), thereby providing a mouse model allowing the assessment
      of gammaH-driven repertoire. Using a tissue array and phage display epitope
      library we report here that IgG repertoire in micro MT/lpr mice is oligo
      monoclonal, bearing self-tissue reactivity. This is supported by analysis of the
      Vkappa utilization in peripheral B cells from micro MT/lpr mice, which revealed a
      strikingly restricted repertoire. In contrast, micro MT/lpr B cells that are
      grown in non-selective BM cultures utilize a wide repertoire. These results
      suggest that the Fas pathway is an important regulator in the generation and
      selection of an autoimmune gammaH-driven repertoire in vivo.

PMID- 15148287
TI  - Toxoplasma gondii infection inhibits the development of lupus-like syndrome in
      autoimmune (New Zealand Black x New Zealand White) F1 mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      presence of autoantibodies and lupus nephritis. In the present study using New
      Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to
      investigate the effects of Toxoplasma gondii infection on the progress of lupus
      nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected
      with T. gondii. The T. gondii infection reduced the number of mice developing
      proteinuria and immune complex deposits in their kidneys and prolonged their life
      span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies,
      especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1
      mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of
      NZBW F1 mice was significantly higher than that in control mice at 9 weeks after
      T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock
      protein 70 (HSP70) monoclonal antibody were substantially protected against the
      onset of glomerulonephritis. Further, down-regulation of intracellular expression
      of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1
      mice. This was consistent with the previous data indicating the involvement of
      Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These
      results suggest that T. gondii infection is capable of preventing the development
      of autoimmune renal disorder in NZBW F1 mice.

PMID- 15148289
TI  - Impairment of B cell receptor-mediated Ca2+ influx, activation of mitogen
      activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells.
AB  - CD72 is a 45 kDa B cell-specific type II transmembrane protein of the C-type
      lectin superfamily. It was originally defined as a receptor-like molecule that
      regulates B cell activation and differentiation; however, its precise function
      remains unclear since more recent functional analyses, including a gene targeting
      study, suggest that CD72 may serve as a negative or a positive regulator of B
      cell signaling. In the present study, we analyzed the cell-autonomous function of
      CD72 in B cell receptor (BCR) signaling using CD72-deficient cells generated from
      mature BAL-17 cells. We found that BCR-mediated phosphorylation of CD19, Btk, Vav
      and phospholipase Cgamma2 and association of CD19 with phosphatidylinositol-3
      kinase were impaired in CD72-deficient cells. Inositol trisphosphate synthesis
      was normally induced initially but ablated at 1 min of stimulation in CD72
      deficient cells. In the event, Ca(2+) release from intracellular stores remained
      intact, though influx of extracellular Ca(2+) was severely impaired in CD72
      deficient cells. Furthermore, BCR-evoked activation of mitogen-activated protein
      kinases (MAPKs), extracellular signal-regulated kinase and c-Jun NH(2)-terminal
      kinase, and growth inhibition in BAL-17 cells were blocked in the absence of
      CD72. Significantly, these effects were largely reversed by re-expression of
      CD72. Thus, CD72 appears to exert a positive effect on BCR signaling pathways
      leading to Ca(2+) influx and MAPK activation, which in turn may determine the
      fate of BAL-17 cells.

PMID- 15148288
TI  - A chimeric T cell receptor with super-signaling properties.
AB  - A key question yet to be resolved concerns the structure and function
      relationship of the TCR complex. How does antigen recognition by the TCR
      alphabeta chains result in the activation of distinct signal transduction
      pathways by the CD3-gammadeltaepsilon/zeta complex? To investigate which part of
      the TCR-beta chain is involved in TCR signaling, we exchanged different domains
      of the constant regions of the TCR-beta chain with the corresponding TCR-gamma
      chain domains. We show here that hybridoma cells expressing a chimeric TCR-beta
      chain (betaIII) containing intracellular and transmembrane TCR-gamma amino acids,
      together with a wild-type TCR-alpha (alphawt) chain, were 10 times more sensitive
      to antigenic stimulation compared to cells expressing TCR-alphawt/betawt chains.
      This super-signaling phenotype of the betaIII chain was observed in two different
      TCRs. One specific for an alloantigen (I-A(bm12)) and one for an autoantigen (I
      A(b)/MOG(35-55)). We found that this chimeric alphawt/betaIII TCR had normal
      association with CD3-gammadeltaepsilon and zeta chains. To investigate the effect
      of the chimeric betaIII chain in transgenic T cells, we made MOG(35-55)-specific
      TCR transgenic mice expressing either the alphawt/betawt or chimeric
      alphawt/betaIII TCR. Similar to what was observed in hybridoma cells, transgenic
      alphawt/betaIII T cells showed a super-signaling phenotype upon antigenic
      stimulation. Further studies may help us understand the effect of increased TCR
      signaling on autoimmunity and may lead to the identification of signaling
      molecules that can be targeted to stop the progression of autoimmune disorders
      such as multiple sclerosis.

PMID- 15148290
TI  - Persistent lowering of pressure by transplanting kidneys from adult spontaneously
      hypertensive rats treated with brief antihypertensive therapy.
AB  - Kidney function is critical in determining the level of arterial pressure and in
      the pathogenesis of hypertension. Important evidence comes from studies in which
      the level of blood pressure is dictated by the donor when kidneys are
      transplanted between genetically hypertensive and normotensive rats. We have
      hypothesized that pharmacotherapy modifies specific properties of the kidney,
      particularly the vasculature, such that after kidney transplantation, there are
      persistent changes in the level of arterial pressure. Consistent with previous
      studies, a 2-week aggressive treatment of adult (15 weeks) spontaneously
      hypertensive rats with an angiotensin-converting enzyme inhibitor (enalapril)
      combined with a low-salt diet induced a persistent change in the kidney and a
      decrease in arterial pressure (18%). These persistent changes in arterial
      pressure could be completely transferred to untreated adult spontaneously
      hypertensive rats by kidney transplantation (ie, pressure in untreated rats was
      decreased after transplantation of a kidney donated from a previously treated
      rat). Further, the importance of kidney-specific changes was demonstrated by
      finding that the treatment-induced lowering of arterial pressure was completely
      reversed by transferring an untreated kidney into a previously treated rat. The
      specific treatment-induced changes to the kidney included a decrease in
      structurally based renal vascular resistance that was similar to the persistent
      lowering of arterial pressure. These data provide evidence for a link between the
      treatment-induced changes in kidney vascular structure and the persistent
      lowering of arterial pressure. The findings also suggest that a key
      pharmacotherapeutic target in hypertension should be kidney-specific changes,
      such as renal vascular structure.

PMID- 15148292
TI  - Sex differences in age-related stiffening of the aorta in subjects with type 2
      diabetes.
AB  - Hypertension and type 2 diabetes are associated with increased aortic pulse wave
      velocity (PWV), a measure of aortic stiffness and a powerful risk factor for
      cardiovascular events. The association of hypertension with type 2 diabetes may
      obscure the degree to which diabetes rather than hypertension contributes to an
      elevated PWV. The objective of this study was to determine whether the presence
      of type 2 diabetes is associated with an elevated PWV compared with nondiabetic
      subjects matched for mean arterial blood pressure. PWV was determined by
      measuring carotid to femoral transit time using applanation tonometry in 186
      subjects (104 women) with (n=93) and without (n=93) type 2 diabetes. Diabetic and
      nondiabetic subjects were matched for age and mean arterial pressure (to +/-5
      years and 5 mm Hg, respectively). PWV was strongly correlated with age and mean
      arterial blood pressure (R=0.59 and 0.29 respectively, each P<0.0001). PWV
      increased significantly more with age in women with diabetes (slope of regression
      line+/-SE: 0.19+/-0.03 m x s(-1) x year(-1)) than in nondiabetic women (0.08+/
      0.02 m x s(-1) x year(-1), P<0.01 for difference). In men, however, the age
      related increase in PWV was similar in diabetic (0.15+/-0.03 m x s(-1) x year(
      1)) and nondiabetic subjects (0.13+/-0.03 m. s(-1) x year(-1), P=NS). The
      interaction of diabetic status with age and with sex was significant (P=0.01).
      Type 2 diabetes is associated with a greater age-related stiffening of the aorta
      in women compared with men, and this is not explained by hypertension.

PMID- 15148291
TI  - Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing
      to hypertension.
AB  - The chloride channel ClC-Kb is expressed in the basolateral cell membrane of the
      distal nephron and participates in renal NaCl reabsorption. Loss-of-function
      mutations of ClC-Kb lead to classic Bartter syndrome, a rare salt-wasting
      disorder. Recently, we identified the ClC-Kb(T481S) polymorphism, which confers a
      strong gain-of-function effect on the ClC-Kb chloride channel. The present study
      has been performed to explore the prevalence of the mutation and its functional
      significance in renal salt handling and blood pressure regulation. As evident
      from electrophysiological analysis with the 2-electrode voltage-clamp technique,
      heterologous expression of ClC-Kb(T481S) in Xenopus oocytes gave rise to a
      current that was 7-fold larger than the current produced by wild-type ClC-Kb. The
      prevalence of the mutant allele was significantly higher in an African population
      from Ghana (22%) than in whites (12%). As tested in 1 white population, carriers
      of ClC-Kb(T481S) were associated with significantly higher systolic (by
      approximately 6.0 mm Hg) and diastolic (by approximately 4.2 mm Hg) blood
      pressures and significantly higher prevalence (45% versus 25%) of hypertensive (>
      or =140/90 mm Hg) blood pressure levels. Individuals carrying ClC-Kb(T481S) had
      significantly higher plasma Na+ concentrations and significantly decreased
      glomerular filtration rate. In conclusion, the mutation ClC-Kb(T481S) of the
      renal epithelial Cl- channel ClC-Kb strongly activates ClC-Kb chloride channel
      function in vitro and may predispose to the development of essential hypertension
      in vivo.

PMID- 15148293
TI  - Neutrophils infiltrate resistance-sized vessels of subcutaneous fat in women with
      preeclampsia.
AB  - We examined if there is systemic vascular inflammation and neutrophil
      infiltration in women with preeclampsia. Resistance-sized vessels (10 to 200
      microm) of subcutaneous fat were evaluated from normal nonpregnant women, normal
      pregnant women, and preeclamptic women. Immunohistochemical staining was
      performed for: (1) interleukin-8 (IL-8), a potent neutrophil chemokine; (2)
      intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial cell adhesion
      molecule; and (3) CD66b, a neutrophil antigen. Vessels of preeclamptic patients
      had intense IL-8 staining in the endothelium and vascular smooth muscle, as
      compared with little or no staining for normal pregnant and normal nonpregnant
      patients. ICAM-1 was expressed on the endothelium of all patient groups. In
      preeclamptic patients, ICAM-1 was also expressed on vascular smooth muscle.
      Vessels of preeclamptic patients had significantly more CD66b staining of
      neutrophils than did normal pregnant or normal nonpregnant patients. There were
      significantly more vessels stained, more vessels with neutrophils flattened and
      adhered to endothelium, more vessels with neutrophils infiltrated into the
      intima, and more neutrophils per vessel. In conclusion, in women with
      preeclampsia, there was significant infiltration of neutrophils into maternal
      systemic vasculature associated with inflammation of the vascular smooth muscle
      indicated by increased expression of IL-8 and ICAM-1. Neutrophil infiltration
      provides a reasonable explanation for endothelial and vascular smooth muscle
      dysfunction in preeclampsia because neutrophils produce toxic substances, which
      may explain clinical symptoms.

PMID- 15148294
TI  - C-reactive protein: risk marker or mediator in atherothrombosis?
AB  - Inflammation appears to be pivotal in all phases of atherosclerosis from the
      fatty streak lesion to acute coronary syndromes. An important downstream marker
      of inflammation is C-reactive protein (CRP). Numerous studies have shown that CRP
      levels predict cardiovascular disease in apparently healthy individuals. This has
      resulted in a position statement recommending cutoff levels of CRP <1.0, 1.0 to
      3.0, and >3.0 mg/L equating to low, average, and high risk for subsequent
      cardiovascular disease. More interestingly, much in vitro data have now emerged
      in support of a role for CRP in atherogenesis. To date, studies largely in
      endothelial cells, but also in monocyte-macrophages and vascular smooth muscle
      cells, support a role for CRP in atherogenesis. The proinflammatory,
      proatherogenic effects of CRP that have been documented in endothelial cells
      include the following: decreased nitric oxide and prostacyclin and increased
      endothelin-1, cell adhesion molecules, monocyte chemoattractant protein-1 and
      interleukin-8, and increased plasminogen activator inhibitor-1. In monocyte
      macrophages, CRP induces tissue factor secretion, increases reactive oxygen
      species and proinflammatory cytokine release, promotes monocyte chemotaxis and
      adhesion, and increases oxidized low-density lipoprotein uptake. Also, CRP has
      been shown in vascular smooth muscle cells to increase inducible nitric oxide
      production, increase NFkappa(b) and mitogen-activated protein kinase activities,
      and, most importantly, upregulate angiotensin type-1 receptor resulting in
      increased reactive oxygen species and vascular smooth muscle cell proliferation.
      Future studies should be directed at delineating the molecular mechanisms for
      these important in vitro observations. Also, studies should be directed at
      confirming these findings in animal models and other systems as proof of concept.
      In conclusion, CRP is a risk marker for cardiovascular disease and, based on
      future studies, could emerge as a mediator in atherogenesis.

PMID- 15148295
TI  - Screening method of carbohydrate-binding proteins in biological sources by
      capillary affinity electrophoresis and its application to determination of Tulipa
      gesneriana agglutinin in tulip bulbs.
AB  - We developed capillary affinity electrophoresis (CAE) to analyze the molecular
      interaction between carbohydrate chains and proteins in solution state. A mixture
      of oligosaccharides derived from a glycoprotein was labeled with 8-aminopyrene
      1,3,6-trisulfonate (APTS), and used as glycan library without isolation.
      Interaction of a carbohydrate-binding protein with each oligosaccharide in the
      mixture could be simultaneously observed, and relative affinities of
      oligosaccharides toward the protein were accurately determined. In this study, we
      applied CAE to detect the presence of lectins in some plants (Japanese elderberry
      bark and tulip bulb). In the crude extract of the elderberry bark, binding
      activity toward sialo-carbohydrate chains could be easily detected. We also
      examined the presence of lectins in the crude extract of tulip bulbs and
      determined the detailed carbohydrate-binding specificity of Tulipa gesneriana
      agglutinin (TGA), one of the lectins from tulip bulbs. Kinetic studies
      demonstrated that TGA showed novel carbohydrate-binding specificity and
      preferentially recognized triantennary oligosaccharides with Gal residues at
      nonreducing termini and a Fuc residue linked through alpha(1-6) linkage at
      chitobiose portion of the reducing termini but not tetraantennary carbohydrates.
      The results described here indicate that CAE will be a valuable method for both
      screening of lectins in natural sources and determination of their detailed
      carbohydrate-binding specificities.

PMID- 15148296
TI  - Thermodynamic binding studies of bivalent oligosaccharides to galectin-1,
      galectin-3, and the carbohydrate recognition domain of galectin-3.
AB  - Galectins are a growing family of animal lectins with common consensus sequences
      that bind beta-Gal and LacNAc residues. There are at present 14 members of the
      galectin family; however, certain galectins possess different structures as well
      as biological properties. Galectin-1 is a dimer of two homologous carbohydrate
      recognition domains (CRDs) and possesses apoptotic and proinvasive activities.
      Galectin-3 consists of a C-terminal CRD and an N-terminal nonlectin domain
      implicated in the oligomerization of the protein and is often associated with
      antiapoptotic activity. Because many cellular oligosaccharide receptors are
      multivalent, it is important to characterize the interactions of multivalent
      carbohydrates with galectins-1 and -3. In the present study, binding of bovine
      heart galectin-1 and recombinant murine galectin-3 to a series of synthetic
      analogs containing two LacNAc residues separated by a varying number of methylene
      groups, as well as biantennary analogs possessing two LacNAc residues, were
      examined using isothermal titration microcalorimetry (ITC) and hemagglutination
      inhibition measurements. The thermodynamics of binding of the multivalent
      carbohydrates to the C-terminal CRD domain of galectin-3 was also investigated.
      ITC results showed that each bivalent analog bound by both LacNAc residues to the
      two galectins. However, galectin-1 shows a lack of enhanced affinity for the
      bivalent straight chain and branched chain analogs, whereas galectin-3 shows
      enhanced affinity for only lacto-N-hexaose, a naturally occurring branched chain
      carbohydrate. The CRD domain of galectin-3 was shown to possess similar
      thermodynamic binding properties as the intact molecule. The results of this
      study have important implications for the design of carbohydrate inhibitors of
      the two galectins.

PMID- 15148298
TI  - Deconstructing the genesis of animal form.
AB  - Santa Fe - with its museums and galleries full of art and crafts inspired by
      natural forms - was the perfect setting for a Keystone conference on vertebrate
      organogenesis in February 2004. Organized by Gail Martin and Cliff Tabin, the
      conference sessions were loosely subdivided into anatomical systems - 'skin,
      hair, teeth', 'pancreas, liver, gut', 'skeleton', and so on. However, from the
      outset, common themes emerged that transcended particular organ systems and
      generated a sense of unity and excitement among the participants.

PMID- 15148297
TI  - Wingless, hedgehog and heparan sulfate proteoglycans.

PMID- 15148299
TI  - Single cell lineage and regionalization of cell populations during Medaka
      neurulation.
AB  - To study the movement of individual cells and development of cell grouping during
      neurogenesis, we labeled single cells in early Medaka gastrula at stage 13 [13
      hours post-fertilization (hpf)] with a fluorescent vital dye, and analyzed cells
      and their descendants using time-lapse live recording up to stage 24 (44 hpf). At
      stage 13, all future neural cells were located in a dorsal 140 degrees sector of
      the embryo, and migrated toward the vegetal pole; but during stage 15 to 16, they
      converged towards the midline. Cells that contributed to later neural
      subdivisions initially formed overlapping populations, but after stage 16+ they
      formed non-overlapping cell groups having characteristics of tissue
      'compartments', preceding development of morphologically distinct neural
      subdivisions. In early retinal development, a single compartment for future
      retinal cells was formed superficial to telencephalic and diencephalic
      compartments, but it was split into left and right eye components at stage 17 in
      parallel with anterodorsal movement of the diencephalic compartment. At stage
      16+, when these compartments were established, Pax6 expression initiated, but
      only in the laterally located subpopulation of the retina precursor. These
      observations revise the current view of bilateral retinal development. Continuous
      live recording of labeled single precursor cells and computer graphics-assisted
      data analysis, which are presented for the first time in this study, provide
      excellent means with which to analyze essential cellular processes in
      organogenesis.

PMID- 15148301
TI  - Cell lineage tracing during Xenopus tail regeneration.
AB  - The tail of the Xenopus tadpole will regenerate following amputation, and all
      three of the main axial structures - the spinal cord, the notochord and the
      segmented myotomes - are found in the regenerated tail. We have investigated the
      cellular origin of each of these three tissue types during regeneration. We
      produced Xenopus laevis embryos transgenic for the CMV (Simian Cytomegalovirus)
      promoter driving GFP (Green Fluorescent Protein) ubiquitously throughout the
      embryo. Single tissues were then specifically labelled by making grafts at the
      neurula stage from transgenic donors to unlabelled hosts. When the hosts have
      developed to tadpoles, they carry a region of the appropriate tissue labelled
      with GFP. These tails were amputated through the labelled region and the
      distribution of labelled cells in the regenerate was followed. We also labelled
      myofibres using the Cre-lox method. The results show that the spinal cord and the
      notochord regenerate from the same tissue type in the stump, with no labelling of
      other tissues. In the case of the muscle, we show that the myofibres of the
      regenerate arise from satellite cells and not from the pre-existing myofibres.
      This shows that metaplasia between differentiated cell types does not occur, and
      that the process of Xenopus tail regeneration is more akin to tissue renewal in
      mammals than to urodele tail regeneration.

PMID- 15148300
TI  - The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit.
AB  - The CNS of bilateral symmetric organisms is characterized by intensive
      contralateral axonal connections. Genetic screens in Drosophila have identified
      only a few genes required for guiding commissural growth cones toward and across
      the midline. Two evolutionarily conserved signaling molecules, Netrin and Slit,
      are expressed in the CNS midline cells. Netrin acts primarily as an attractive
      signaling cue, whereas Slit mediates repulsive functions. Here, we describe a
      detailed analysis of the Drosophila gene schizo, which is required for commissure
      formation. schizo leads to a commissural phenotype reminiscent of netrin mutant
      embryos. Double-mutant analyses indicate that Netrin and Schizo act
      independently. The schizo mutant phenotype can be suppressed by either expressing
      netrin in the CNS midline cells or by a reduction of the slit gene dose,
      indicating that the balance of attractive and repulsive signaling is impaired in
      schizo mutants. Overexpression of the schizo RNA in the CNS midline using the
      GAL4/UAS system leads to a slit phenocopy, suggesting that schizo primarily
      antagonizes Slit signaling. This is further supported by cell type-specific
      rescue experiments. The schizo gene generates at least two proteins containing a
      conserved Sec7 and a pleckstrin homology domain (PH) characteristic for guanine
      nucleotide exchange factors (GEF) acting on ARF GTPases, which are known to
      regulate endocytosis. In support of the notion that schizo regulates Slit
      expression via endocytosis, we found that block of endocytosis leads to a schizo
      like phenotype. We thus propose that the balance of the two signaling cues Netrin
      and Slit can be regulated, controlling membrane dynamics.

PMID- 15148302
TI  - Control of roof plate formation by Lmx1a in the developing spinal cord.
AB  - Numerous studies have identified the roof plate as an embryonic signaling center
      critical for dorsal central nervous system patterning, but little is known about
      mechanisms that control its formation and its separation from clonally related
      neural crest cells and dI1 sensory interneurons. We demonstrate that the LIM
      homeodomain transcription factor, Lmx1a, mutated in the dreher mouse, acts to
      withdraw dorsal spinal cord progenitors from the cell cycle and simultaneously
      direct their differentiation into functional roof plate cells. Lmx1a cell
      autonomously represses the dI1 progenitor fate, distinguishing the roof plate and
      dI1 interneuron programs, two major developmental programs of the dorsal neural
      tube. Lmx1a is not directly involved in neural crest development. We establish
      that Bmp signaling from epidermal ectoderm is necessary and sufficient for
      inducing Lmx1a and other co-factors that also regulate the extent of roof plate
      induction. We conclude that Lmx1a controls multiple aspects of dorsal midline
      patterning and is a major mediator of early Bmp signaling in the developing
      spinal cord.

PMID- 15148303
TI  - Unique and overlapping functions of pRb and p107 in the control of proliferation
      and differentiation in epidermis.
AB  - The retinoblastoma gene product, pRb, plays a crucial role in cell cycle
      regulation, differentiation and inhibition of oncogenic transformation. pRb and
      its closely related family members p107 and p130 perform exclusive and
      overlapping functions during mouse development. The embryonic lethality of Rb
      null animals restricts the phenotypic analysis of these mice to mid-gestation
      embryogenesis. We employed the Cre/loxP system to study the function of Rb in
      adult mouse stratified epithelium. Rb(F19/F19);K14cre mice displayed hyperplasia
      and hyperkeratosis in the epidermis with increased proliferation and aberrant
      expression of differentiation markers. In vitro, pRb is essential for the
      maintainance of the postmitotic state of terminally differentiated keratinocytes,
      preventing cell cycle re-entry. However, p107 compensates for the effects of Rb
      loss as the phenotypic abnormalities of Rb(F19/F19);K14cre keratinocytes in vivo
      and in vitro become more severe with the concurrent loss of p107 alleles. p107
      alone appears to be dispensable for all these phenotypic changes, as the presence
      of a single Rb allele in a p107-null background rescues all these alterations.
      Luciferase reporter experiments indicate that these phenotypic alterations might
      be mediated by increased E2F activity. Our findings support a model in which pRb
      in conjunction with p107 plays a central role in regulating epidermal
      homeostasis.

PMID- 15148305
TI  - Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
AB  - Fat cadherins form a distinct subfamily of the cadherin gene superfamily, and are
      featured by their unusually large extracellular domain. In this work, we
      investigated the function of a mammalian Fat cadherin. Fat1 was localized at
      filopodial tips, lamellipodial edges, and cell-cell boundaries, overlapping with
      dynamic actin structures. RNA interference-mediated knockdown of Fat1 resulted in
      disorganization of cell junction-associated F-actin and other actin
      fibers/cables, disturbance of cell-cell contacts, and also inhibition of cell
      polarity formation at wound margins. Furthermore, we identified Ena/vasodilator
      stimulated phosphoproteins as a potential downstream effector of Fat1. These
      results suggest that Fat1 regulates actin cytoskeletal organization at cell
      peripheries, thereby modulating cell contacts and polarity.

PMID- 15148304
TI  - A hierarchical order of factors in the generation of FLK1- and SCL-expressing
      hematopoietic and endothelial progenitors from embryonic stem cells.
AB  - The receptor tyrosine kinase FLK1 and the transcription factor SCL play crucial
      roles in the establishment of hematopoietic and endothelial cell lineages in
      mice. We have previously used an in vitro differentiation model of embryonic stem
      (ES) cells and demonstrated that hematopoietic and endothelial cells develop via
      sequentially generated FLK1(+) and SCL(+) cells. To gain a better understanding
      of cellular and molecular events leading to hematopoietic specification, we
      examined factors necessary for FLK1(+) and SCL(+) cell induction in serum-free
      conditions. We demonstrate that bone morphogenetic protein (BMP) 4 was required
      for the generation of FLK1(+) and SCL(+) cells, and that vascular endothelial
      growth factor (VEGF) was necessary for the expansion and differentiation of SCL
      expressing hematopoietic progenitors. Consistently, Flk1-deficient ES cells
      responded to BMP4 and generated TER119(+) and CD31(+) cells, but they failed to
      expand in response to VEGF. The Smad1/5 and map kinase pathways were activated by
      BMP4 and VEGF, respectively. The overexpression of SMAD6 in ES cells resulted in
      a reduction of FLK1(+) cells. In addition, a MAP kinase kinase 1 specific
      inhibitor blocked the expansion of SCL(+) cells in response to VEGF. Finally,
      VEGF mediated expansion of hematopoietic and endothelial cell progenitors was
      inhibited by TGFbeta1, but was augmented by activin A. Our studies suggest that
      hematopoietic and endothelial commitment from the mesoderm occurs via BMP4
      mediated signals and that expansion and/or differentiation of such progenitors is
      achieved by an interplay of VEGF, TGFbeta1 and activin A signaling.

PMID- 15148306
TI  - Calcineurin initiates smooth muscle differentiation in neural crest stem cells.
AB  - The process of vascular smooth muscle cell (vSMC) differentiation is critical to
      embryonic angiogenesis. However, despite its importance, the vSMC differentiation
      program remains largely undefined. Murine gene disruption studies have identified
      several gene products that are necessary for vSMC differentiation, but these
      methodologies cannot establish whether or not a factor is sufficient to initiate
      the differentiation program. A gain-of-function system consisting of normal vSMC
      progenitor cells would serve as a useful complement to whole animal loss-of
      function studies. We use such a system here, namely freshly isolated rat neural
      crest stem cells (NCSCs), to show that activation of the calcineurin signaling
      pathway is sufficient to drive these cells toward a smooth muscle fate. In
      addition, we present data suggesting that transforming growth factor (TGF)-beta1,
      which also causes NCSCs to differentiate into smooth muscle, activates
      calcineurin signaling in NCSCs, leading to a model in which activation of
      calcineurin signaling is the mechanism by which TGF-beta1 causes SMC
      differentiation in these cells.

PMID- 15148307
TI  - Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic
      of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder.
AB  - Mutations in the gene of the peripheral myelin protein zero (P0) give rise to the
      peripheral neuropathies Charcot-Marie-Tooth type 1B disease (CMT1B), Dejerine
      Sottas syndrome, and congenital hypomyelinating neuropathy. To investigate the
      pathomechanisms of a specific point mutation in the P0 gene, we generated two
      independent transgenic mouse lines expressing the pathogenic CMT1B missense
      mutation Ile106Leu (P0sub) under the control of the P0 promoter on a wild-type
      background. Both P0sub-transgenic mouse lines showed shivering and
      ultrastructural abnormalities including retarded myelination, onion bulb
      formation, and dysmyelination seen as aberrantly folded myelin sheaths and
      tomacula in all nerve fibers. Functionally, the mutation leads to dispersed
      compound muscle action potentials and severely reduced conduction velocities. Our
      observations support the view that the Ile106Leu mutation acts by a dominant
      negative gain of function and that the P0sub-transgenic mouse represents an
      animal model for a severe, tomaculous form of CMT1B.

PMID- 15148310
TI  - The ferric uptake regulator (Fur) protein from Bradyrhizobium japonicum is an
      iron-responsive transcriptional repressor in vitro.
AB  - The Fur protein represses transcription of iron-responsive genes in bacteria. The
      discovery that Fur is a zinc metalloprotein and the use of surrogate metals for
      Fe(2+) for in vitro studies question whether Fur is a direct iron sensor. In the
      present study, we show that the affinity of Fur from Bradyrhizobium japonicum
      (BjFur) for its target DNA increases 30-fold in the presence of metal, with a
      K(d) value of about 2 nM. DNase I footprinting experiments showed that BjFur
      protected its binding site within the irr gene promoter in the presence of Fe(2+)
      but not in the absence of metal, showing that DNA binding is Fe(2+)-dependent.
      BjFur did not inhibit in vitro transcription from the irr promoter using purified
      components in the absence of metal, but BjFur repressed transcription in the
      presence of Fe(2+). Thus, BjFur is an iron-responsive transcriptional repressor
      in vitro. A regulatory Fe(2+)-binding site (site 1) and a structural Zn(2+)
      binding site (site 2) inferred from the recent crystal structure of Fur from
      Pseudomonas aeruginosa are composed of amino acids highly conserved in many Fur
      proteins, including BjFur. BjFur mutants containing substitutions in site 1
      (BjFurS1) or site 2 (BjFurS2) bound DNA with high affinity and repressed
      transcription in vitro in an Fe(2+)-dependent manner. Interestingly, only a
      single dimer of BjFurS2 occupied the irr promoter, whereas the wild type and
      BjFurS1 displayed one- or two-dimer occupancy. We suggest that the putative
      functions for metal-binding sites deduced from the structure of P. aeruginosa Fur
      cannot be extrapolated to bacterial Fur proteins as a whole.

PMID- 15148309
TI  - Carbohydrate-carbohydrate interaction provides adhesion force and specificity for
      cellular recognition.
AB  - The adhesion force and specificity in the first experimental evidence for cell
      cell recognition in the animal kingdom were assigned to marine sponge cell
      surface proteoglycans. However, the question whether the specificity resided in a
      protein or carbohydrate moiety could not yet be resolved. Here, the strength and
      species specificity of cell-cell recognition could be assigned to a direct
      carbohydrate-carbohydrate interaction. Atomic force microscopy measurements
      revealed equally strong adhesion forces between glycan molecules (190-310
      piconewtons) as between proteins in antibody-antigen interactions (244
      piconewtons). Quantitative measurements of adhesion forces between glycans from
      identical species versus glycans from different species confirmed the species
      specificity of the interaction. Glycan-coated beads aggregated according to their
      species of origin, i.e., the same way as live sponge cells did. Live cells also
      demonstrated species selective binding to glycans coated on surfaces. These
      findings confirm for the first time the existence of relatively strong and
      species-specific recognition between surface glycans, a process that may have
      significant implications in cellular recognition.

PMID- 15148308
TI  - c-Abl phosphorylates Dok1 to promote filopodia during cell spreading.
AB  - Filopodia are dynamic F-actin structures that cells use to explore their
      environment. c-Abl tyrosine kinase promotes filopodia during cell spreading
      through an unknown mechanism that does not require Cdc42 activity. Using an
      unbiased approach, we identified Dok1 as a specific c-Abl substrate in spreading
      fibroblasts. When activated by cell adhesion, c-Abl phosphorylates Y361 of Dok1,
      promoting its association with the Src homology 2 domain (SH2)/SH3 adaptor
      protein Nck. Each signaling component was critical for filopodia formation during
      cell spreading, as evidenced by the finding that mouse fibroblasts lacking c-Abl,
      Dok1, or Nck had fewer filopodia than cells reexpressing the product of the
      disrupted gene. Dok1 and c-Abl stimulated filopodia in a mutually interdependent
      manner, indicating that they function in the same signaling pathway. Dok1 and c
      Abl were both detected in filopodia of spreading cells, and therefore may act
      locally to modulate actin. Our data suggest a novel pathway by which c-Abl
      transduces signals to the actin cytoskeleton through phosphorylating Dok1 Y361
      and recruiting Nck.

PMID- 15148312
TI  - The Src family of tyrosine kinases is important for embryonic stem cell self
      renewal.
AB  - cYes, a member of the Src family of non-receptor tyrosine kinases, is highly
      expressed in mouse and human embryonic stem (ES) cells. We demonstrate that cYes
      kinase activity is regulated by leukemia inhibitory factor (LIF) and serum and is
      down-regulated when cells differentiate. Moreover, selective chemical inhibition
      of Src family kinases decreases growth and expression of stem cell genes that
      mark the undifferentiated state, including Oct3/4, alkaline phosphatase,
      fibroblast growth factor 4, and Nanog. A synergistic effect on differentiation is
      observed when ES cells are cultured with an Src family inhibitor and low levels
      of retinoic acid. Src family kinase inhibition does not interfere with LIF
      induced JAK/STAT3 (Janus-associated tyrosine kinases/signal transducer and
      activator of transcription 3) or p42/p44 MAPK (mitogen-activated protein kinase)
      phosphorylation. Together the results suggest that the activation of the Src
      family is important for maintaining mouse and human ES in an undifferentiated
      state and may represent a third, independent pathway, downstream of LIF in mouse
      ES cells.

PMID- 15148311
TI  - Alternating access and a pore-loop structure in the Na+-citrate transporter CitS
      of Klebsiella pneumoniae.
AB  - CitS of Klebsiella pneumoniae is a secondary transporter that transports citrate
      in symport with 2 Na(+) ions. Reaction of Cys-398 and Cys-414, which are located
      in a cytoplasmic loop of the protein that is believed to be involved in
      catalysis, with thiol reagents resulted in significant inhibition of uptake
      activity. The reactivity of the two residues was determined in single Cys mutants
      in different catalytic states of the transporter and from both sides of the
      membrane. The single Cys mutants were shown to have the same transport
      stoichiometry as wild type CitS, but the C398S mutation was responsible for a 10
      fold loss of affinity for Na(+). Both cysteine residues were accessible from the
      periplasmic as well as from the cytoplasmic side of the membrane by the membrane
      impermeable thiol reagent [2-(trimethylammonium)ethyl] methanethiosulfonate
      bromide (MTSET) suggesting that the residues are part of the translocation site.
      Binding of citrate to the outward facing binding site of the transporter resulted
      in partial protection against inactivation by N-ethylmaleimide, whereas binding
      to the inward facing binding site resulted in essentially complete protection. A
      10-fold higher concentration of citrate was required at the cytoplasmic rather
      than at the periplasmic side of the membrane to promote protection. Only marginal
      effects of citrate binding were seen on reactivity with MTSET. Binding of Na(+)
      at the periplasmic side of the transporter protected both Cys-398 and Cys-414
      against reaction with the thiol reagents, whereas binding at the cytoplasmic side
      was less effective and discriminated between Cys-398 and Cys-414. A model is
      presented in which part of the cytoplasmic loop containing Cys-398 and Cys-414
      folds back into the translocation pore as a pore-loop structure. The loop
      protrudes into the pore beyond the citrate-binding site that is situated at the
      membrane-cytoplasm interface.

PMID- 15148313
TI  - Identification of mPer1 phosphorylation sites responsible for the nuclear entry.
AB  - Casein kinase 1 epsilon (CK1 epsilon) is an essential component of the circadian
      clock in mammals and Drosophila. The phosphorylation of Period (Per) proteins by
      CK1 epsilon is believed to be implicated in their subcellular localization and
      degradation, but the precise mechanism by which CK1 epsilon affects Per proteins
      has not been determined. In this study, three putative CK1 epsilon
      phosphorylation motif clusters in mouse Per1 (mPer1) were identified, and the
      phosphorylation status of serine and threonine residues in these clusters was
      examined. Phosphorylation of residues within a region defined by amino acids 653
      663 and in particular of Ser-661 and Ser-663, was identified as responsible for
      the nuclear translocation of mPer1. Furthermore, phosphorylation of these
      residues may influence the nuclear translocation of a clock protein complex
      containing mPer1. These findings indicate that mPer1 phosphorylation is a
      critical aspect of the circadian clock mechanism.

PMID- 15148314
TI  - Crystal structure of unsaturated glucuronyl hydrolase, responsible for the
      degradation of glycosaminoglycan, from Bacillus sp. GL1 at 1.8 A resolution.
AB  - Unsaturated glucuronyl hydrolase (UGL) is a novel glycosaminoglycan hydrolase
      that releases unsaturated d-glucuronic acid from oligosaccharides produced by
      polysaccharide lyases. The x-ray crystallographic structure of UGL from Bacillus
      sp. GL1 was first determined by multiple isomorphous replacement (mir) and
      refined at 1.8 A resolution with a final R-factor of 16.8% for 25 to 1.8 A
      resolution data. The refined UGL structure consists of 377 amino acid residues
      and 478 water molecules, four glycine molecules, two dithiothreitol (DTT)
      molecules, and one 2-methyl-2,4-pentanediol (MPD) molecule. UGL includes an
      alpha(6)/alpha(6)-barrel, whose structure is found in the six-hairpin enzyme
      superfamily of an alpha/alpha-toroidal fold. One side of the UGL
      alpha(6)/alpha(6)-barrel structure consists of long loops containing three short
      beta-sheets and contributes to the formation of a deep pocket. One glycine
      molecule and two DTT molecules surrounded by highly conserved amino acid residues
      in UGLs were found in the pocket, suggesting that catalytic and substrate-binding
      sites are located in this pocket. The overall UGL structure, with the exception
      of some loops, very much resembled that of the Bacillus subtilis hypothetical
      protein Yter, whose function is unknown and which exhibits little amino acid
      sequence identity with UGL. In the active pocket, residues possibly involved in
      substrate recognition and catalysis by UGL are conserved in UGLs and Yter. The
      most likely candidate catalytic residues for glycosyl hydrolysis are Asp(88) and
      Asp(149). This was supported by site-directed mutagenesis studies in Asp(88) and
      Asp(149).

PMID- 15148316
TI  - Recognition of fold and sugar linkage for glycosyltransferases by multivariate
      sequence analysis.
AB  - Glycosyltransferases (GTs) are among the largest groups of enzymes found and are
      usually classified on the basis of sequence comparisons into many families of
      varying similarity (CAZy systematics). Only two different Rossman-like folds have
      been detected (GT-A and GT-B) within the small number of established crystal
      structures. A third uncharacterized fold has been indicated with transmembrane
      organization (GT-C). We here use a method based on multivariate data analyses
      (MVDAs) of property patterns in amino acid sequences and can with high accuracy
      recognize the correct fold in a large data set of GTs. Likewise, a retaining or
      inverting enzymatic mechanism for attachment of the donor sugar could be properly
      revealed in the GT-A and GT-B fold group sequences by such analyses. Sequence
      alignments could be correlated to important variables in MVDA, and the separating
      amino acid positions could be mapped over the active sites. These seem to be
      localized to similar positions in space for the alpha/beta/alpha binding motifs
      in the GT-B fold group structures. Analogous, active-site sequence positions were
      found for the GT-A fold group. Multivariate property patterns could also easily
      group most GTs annotated in the genomes of Escherichia coli and Synechocystis to
      proper fold or organization group, according to benchmarking comparisons at the
      MetaServer. We conclude that the sequence property patterns revealed by the
      multivariate analyses seem more conserved than amino acid types for these GT
      groups, and these patterns are also conserved in the structures. Such patterns
      may also potentially define substrate preferences.

PMID- 15148315
TI  - Cross-talk between the paired domain and the homeodomain of Pax3: DNA binding by
      each domain causes a structural change in the other domain, supporting
      interdependence for DNA Binding.
AB  - The Pax3 protein has two DNA binding domains, a Paired domain (PD) and a paired
      type Homeo domain (HD). Although the PD and HD can bind to cognate DNA sequences
      when expressed individually, genetic and biochemical data indicate that the two
      domains are functionally interdependent in intact Pax3. The mechanistic basis of
      this functional interdependence is unknown and was studied by protease
      sensitivity. Pax3 was modified by the creation of Factor Xa cleavage sites at
      discrete locations in the PD, the HD, and in the linker segment joining the PD
      and the HD (Xa172, Xa189, and Xa216) in individual Pax3 mutants. The effect of
      Factor Xa insertions on protein stability and on DNA binding by the PD and the HD
      was measured using specific target site sequences. Independent insertions at
      position 100 in the linker separating the first from the second helix-turn-helix
      motif of the PD and at position 216 immediately upstream of the HD were found to
      be readily accessible to Factor Xa cleavage. The effect of DNA binding by the PD
      or the HD on accessibility of Factor Xa sites inserted in the same or in the
      other domain was monitored and quantitated for multiple mutants bearing different
      numbers of Xa sites at each position. In general, DNA binding reduced
      accessibility of all sites, suggesting a more compact and less solvent-exposed
      structure of DNA-bound versus DNA-free Pax3. Results of dose response and time
      course experiments were consistent and showed that DNA binding by the PD not only
      caused a local structural change in the PD but also caused a conformational
      change in the HD (P3OPT binding to Xa216 mutants); similarly, DNA binding by the
      HD also caused a conformational change in the PD (P2 binding to Xa100 mutants).
      These results provide a structural basis for the functional interdependence of
      the two DNA binding domains of Pax3.

PMID- 15148318
TI  - Endoglin regulates cytoskeletal organization through binding to ZRP-1, a member
      of the Lim family of proteins.
AB  - Endoglin is a component of the transforming growth factor-beta receptor complex
      abundantly expressed at the surface of endothelial cells and plays an important
      role in cardiovascular development and vascular remodeling. By using the
      cytoplasmic domain of endoglin as a bait for screening protein interactors, we
      have identified ZRP-1 (zyxin-related protein 1), a 476-amino acid member that
      belongs to a family of LIM containing proteins that includes zyxin and lipoma
      preferred partner. The endoglin interacting region was mapped within the three
      double zinc finger LIM domains of the ZRP-1 C terminus. Analysis of the
      subcellular distribution of ZRP-1 demonstrated that in the absence of endoglin,
      ZRP-1 mainly localizes to focal adhesion sites, whereas in the presence of
      endoglin ZRP-1 is found along actin stress fibers. Because the LIM family of
      proteins has been shown to associate with the actin cytoskeleton, we investigated
      the possibility of a regulatory role for endoglin with regard to this structure.
      Expression of endoglin resulted in a dramatic reorganization of the actin
      cytoskeleton. In the absence of endoglin, F-actin was localized to dense
      aggregates of bundles, whereas in the presence of endoglin, expressed in
      endothelial cells, F-actin was in stress fibers and colocalized with ZRP-1.
      Furthermore, small interfering RNA-mediated suppression of endoglin or ZRP-1, or
      clustering of endoglin in endothelial cells, led to mislocalization of F-actin
      fibers. These results suggest a regulatory role for endoglin, via its interaction
      with ZRP-1, in the actin cytoskeletal organization.

PMID- 15148317
TI  - Structural determinants of substrate specificity in family 1 beta-glucosidases:
      novel insights from the crystal structure of sorghum dhurrinase-1, a plant beta
      glucosidase with strict specificity, in complex with its natural substrate.
AB  - Plant beta-glucosidases play a crucial role in defense against pests. They
      cleave, with variable specificity, beta-glucosides to release toxic aglycone
      moieties. The Sorghum bicolor beta-glucosidase isoenzyme Dhr1 has a strict
      specificity for its natural substrate dhurrin (p-hydroxy-(S)-mandelonitrile-beta
      D-glucoside), whereas its close homolog, the maize beta-glucosidase isoenzyme
      Glu1, which shares 72% sequence identity, hydrolyzes a broad spectrum of
      substrates in addition to its natural substrate 2-O-beta-D-glucopyranosyl-4
      hydroxy-7-methoxy-1,4-benzoxaxin-3-one. Structural data from enzyme.substrate
      complexes of Dhr1 show that the mode of aglycone binding differs from that
      previously observed in the homologous maize enzyme. Specifically, the data
      suggest that Asn(259), Phe(261), and Ser(462), located in the aglycone-binding
      site of S. bicolor Dhr1, are crucial for aglycone recognition and binding. The
      tight binding of the aglycone moiety of dhurrin promotes the stabilization of the
      reaction intermediate in which the glycone moiety is in a deformed (1)S(3)
      conformation within the glycone-binding site, ready for nucleophilic attack to
      occur. Compared with the broad specificity maize beta-glucosidase, this different
      binding mode explains the narrow specificity of sorghum dhurrinase-1.

PMID- 15148319
TI  - Essential role of methionine residues in calmodulin binding to Bordetella
      pertussis adenylate cyclase, as probed by selective oxidation and repair by the
      peptide methionine sulfoxide reductases.
AB  - Bordetella pertussis, the causative agent of whooping cough, secretes among other
      virulence factors an adenylate cyclase (AC) toxin that is able to enter into
      eukaryotic cells where it is activated upon binding to endogenous calmodulin
      (CaM) and synthesizes supraphysiological cAMP levels. In vivo, the AC toxin,
      through its specific interaction with the CD11b/CD18 integrin, primarily targets
      phagocytic cells such as neutrophils and macrophages. Because neutrophil priming
      and activation result in the production of reactive oxygen species that may cause
      intracellular oxidation, we have examined the biological consequences of the
      oxidation of CaM methionines upon its interaction with AC. We show here that the
      interaction of CaM with AC is dependent on the reduced state of methionines,
      because oxidation of all methionine residues of CaM dramatically decreases its
      affinity for AC. Peptide methionine sulfoxide reductases A (MsrA) and B (MsrB)
      were able to partially reduce the oxidized CaM, and these partially "repaired"
      forms could interact with AC nearly as efficiently as the native protein. We
      further showed that the CaM.AC complex is resistant to oxidation with tert
      butylhydroperoxide, and we identified methionine residues 109, 124, and 145 as
      critical for binding to AC. The resistance of the AC.CaM complex to oxidation and
      the ability of AC to be efficiently activated by partially oxidized CaM molecules
      should allow the toxin to exert its cytotoxic effects on activated neutrophils
      and contribute to the host colonization.

PMID- 15148320
TI  - Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic
      mechanisms of pancreatic islet pyruvate response.
AB  - Glucose-stimulated insulin secretion is a multistep process dependent on beta
      cell metabolic flux. Our previous studies on intact pancreatic islets used two
      photon NAD(P)H imaging as a quantitative measure of the combined redox signal
      from NADH and NADPH (referred to as NAD(P)H). These studies showed that pyruvate,
      a non-secretagogue, enters beta-cells and causes a transient rise in NAD(P)H. To
      further characterize the metabolic fate of pyruvate, we have now developed one
      photon flavoprotein microscopy as a simultaneous assay of lipoamide dehydrogenase
      (LipDH) autofluorescence. This flavoprotein is in direct equilibrium with
      mitochondrial NADH. Hence, a comparison of LipDH and NAD(P)H autofluorescence
      provides a method to distinguish the production of NADH, NADPH, or both. Using
      this method, the glucose dose response is consistent with an increase in both
      NADH and NADPH. In contrast, the transient rise in NAD(P)H observed with pyruvate
      stimulation is not accompanied by a significant change in LipDH, which indicates
      that pyruvate raises cellular NADPH without raising NADH. In comparison, methyl
      pyruvate stimulated a robust NADH and NADPH response. These data provide new
      evidence that exogenous pyruvate does not induce a significant rise in
      mitochondrial NADH. This inability likely results in its failure to produce the
      ATP necessary for stimulated secretion of insulin. Overall, these data are
      consistent with either a restricted pyruvate dehydrogenase-dependent metabolism
      or a buffering of the NADH response by other metabolic mechanisms.

PMID- 15148321
TI  - Roles for the MH2 domain of Smad7 in the specific inhibition of transforming
      growth factor-beta superfamily signaling.
AB  - Signals by cytokines of the transforming growth factor-beta (TGF-beta)
      superfamily are negatively regulated by inhibitory Smads (I-Smads). Smad7
      inhibits signaling by both TGF-beta and bone morphogenetic proteins (BMPs),
      whereas Smad6 inhibits TGF-beta signals less effectively. I-Smads have amino
      terminal N domains and carboxyl-terminal Mad homology 2 (MH2) domains. The N
      domains are essential for specific inhibition of TGF-beta signaling by Smad7,
      whereas the MH2 domains of I-Smads are involved in the inhibition of TGF-beta
      superfamily signals through interaction with type I receptors. Here, we have
      identified four basic amino acid residues (Lys-312, Lys-316, Lys-401, and Arg
      409) in the basic surface of the Smad7 MH2 domain that play important roles in
      interaction with type I receptors. Mutations of the four basic amino acid
      residues to acidic residues (K312E, K316E, K401E, and R409E) abolished the
      interaction of Smad7 with TGF-beta type I receptors, inhibition of Smad2
      phosphorylation and transcriptional responses induced by TGF-beta, and induction
      of target genes of endogenous activin/Nodal signals in Xenopus early embryos. The
      K401E and R409E mutants of Smad7 were also unable to interact with BMP type I
      receptors (BMPR-I), repress the Smad5 phosphorylation and transcription induced
      by BMP, and effectively inhibit endogenous BMP signals in Xenopus early embryos.
      However, the K312E and K316E mutants were able to interact with BMPR-I and
      retained the ability to inhibit BMP signaling. Thus, the MH2 domain of Smad7
      plays important roles in specific inhibition of TGF-beta superfamily signals
      through differential interaction with type I receptors.

PMID- 15148322
TI  - Translocation of full-length Bid to mitochondria during anoikis.
AB  - Epithelial cells require adhesion to the extracellular matrix for survival, and
      in the absence of adhesion they undergo apoptosis (anoikis). This is distinct
      from apoptosis induced by extracellular death ligands, such as tumor necrosis
      factor, which result in direct activation of caspase 8. Bid is a member of the
      BH3-only subfamily of the Bcl-2 proteins and is important for most cell types to
      apoptose in response to Fas and tumor necrosis factor receptor activation.
      Caspase 8 cleaves full-length Bid, resulting in truncated p15 tBid. p15 tBid is
      potently apoptotic and activates the multidomain Bcl-2 protein, Bax, resulting in
      release of cytochrome c from mitochondria. We have previously shown that Bax
      rapidly translocates from the cytosol to mitochondria following loss of adhesion
      and that this is required for anoikis. We have now examined the role of Bid in
      anoikis. Bid translocates to mitochondria with identical kinetics as Bax.
      Although Bid is required for anoikis, it does not require proteolytic cleavage by
      caspase 8. Furthermore, it does not require Bid to interact directly with other
      Bcl-2 family proteins, such as Bax. Our data indicate that Bid is important for
      regulating apoptosis via the intrinsic pathway and has implications for how Bid
      may fulfill that role.

PMID- 15148323
TI  - Increased susceptibility of mice lacking Clara cell 10-kDa protein to lung
      tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent
      carcinogen in cigarette smoke.
AB  - Ninety percent of all human lung cancers are related to cigarette smoking. Both
      tobacco smoke and lung tumorigenesis are associated with drastically reduced
      levels of Clara cell 10-kDa protein (CC10), a multifunctional secreted protein,
      naturally produced by the airway epithelia of virtually all mammals. We
      previously reported that the expression of CC10 is markedly reduced in animals
      exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, a potent
      carcinogen in tobacco smoke. Furthermore, it has been reported that CC10
      expression, induced in certain tumor cells, reverses the transformed phenotype.
      We demonstrate here that NNK exposure of CC10-knock-out (CC10-KO) mice causes a
      significantly higher incidence of airway epithelial hyperplasia and lung adenomas
      compared with wild type (WT) littermates (30% CC10-KO versus 5% WT, p = 0.041).
      We also found that compared with NNK-treated WT mice, CC10-KO mice manifest
      increased frequency of K-ras mutation, elevated level of Fas ligand (FasL)
      expression, and increased MAPK/Erk phosphorylation, all of which are considered
      predisposing events in NNK-induced lung tumorigenesis. We propose that CC10 has a
      protective role against NNK-induced lung tumorigenesis mediated via down
      regulation of the above-mentioned predisposing events.

PMID- 15148324
TI  - Selenium-containing 15-mer peptides with high glutathione peroxidase-like
      activity.
AB  - Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a
      variety of organisms. Here we described a new strategy for generating a novel GPX
      mimic by combination of a phage-displayed random 15-mer peptide library followed
      by computer-aided rational design and chemical mutation. The novel GPX mimic is a
      homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic
      center, a specific binding site for substrates, and high catalytic efficiency.
      Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH)
      and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the
      highest among the existing GPX mimics. Moreover, the novel GPX mimic was
      confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by
      measuring the content of malondialdehyde, cell viability, and lactate
      dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the
      cell membrane because of its small molecular size. These characteristics endue
      the novel mimic with potential perspective for pharmaceutical applications.

PMID- 15148326
TI  - Inhibition of nitric-oxide synthase-I (NOS-I)-dependent nitric oxide production
      by lipopolysaccharide plus interferon-gamma is mediated by arachidonic acid.
      Effects on NFkappaB activation and late inducible NOS expression.
AB  - Previous results have indicated that lipopolysaccharide (LPS) plus interferon
      gamma (IFNgamma) inhibits nitric-oxide synthase (NOS)-I activity in glial cells.
      We report here that arachidonic acid (AA) plays a pivotal role in this response,
      which was consistently reproduced in different glial cell lines and in primary
      rat astrocytes. This notion was established using pharmacological inhibitors of
      phospholipase A2 (PLA2), cytosolic PLA2 (cPLA2) antisense oligonucleotides, and
      AA add-back experiments. This approach not only allowed the demonstration that AA
      promotes inhibition of NOS-I activity but also produced novel experimental
      evidence that LPS/IFNgamma itself is a potential stimulus for NOS-I. Indeed,
      LPS/IFNgamma fails to generate nitric oxide (NO) via NOS-I activation simply
      because it activates the AA-dependent signal that impedes NOS-I activity.
      Otherwise, LPS/IFNgamma promotes NO formation, sensitive to exogenous AA, in
      cells in which cPLA2 is pharmacologically inhibited or genetically depleted.
      Because NO suppresses the NFkappaB-dependent NOS-II expression, inactivation of
      NOS-I by the LPS/IFNgamma-induced AA pathway provides optimal conditions for
      NFkappaB activation and subsequent NOS-II expression. Inhibition of cPLA2
      activity, while reducing the availability of AA, consistently inhibited NFkappaB
      activation and NOS-II mRNA induction and delayed NO formation. These responses
      were promptly reestablished by addition of exogenous AA. Finally, we have
      demonstrated that the LPS/IFNgamma-dependent tyrosine phosphorylation of NOS-I
      and inhibition of its activity are mediated by endogenous AA.

PMID- 15148325
TI  - Differential expression of cholesterol hydroxylases in Alzheimer's disease.
AB  - Cholesterol is eliminated from neurons by oxidization, which generates
      oxysterols. Cholesterol oxidation is mediated by the enzymes cholesterol 24
      hydroxylase (CYP46A1) and cholesterol 27-hydroxylase (CYP27A1).
      Immunocytochemical studies show that CYP46A1 and CYP27A1 are expressed in neurons
      and some astrocytes in the normal brain, and CYP27A1 is present in
      oligodendrocytes. In Alzheimer's disease (AD), CYP46A1 shows prominent expression
      in astrocytes and around amyloid plaques, whereas CYP27A1 expression decreases in
      neurons and is not apparent around amyloid plaques but increases in
      oligodendrocytes. Although previous studies have examined the effects of
      synthetic oxysterols on the processing of amyloid precursor protein (APP), the
      actions of the naturally occurring oxysterols have yet to be examined. To
      understand the role of cholesterol oxidation in AD, we compared the effects of
      24(S)- and 27-hydroxycholesterol on the processing of APP and analyzed the cell
      specific expression patterns of the two cholesterol hydroxylases in the human
      brain. Both oxysterols inhibited production of Abeta in neurons, but 24(S)
      hydroxycholesterol was approximately 1000-fold more potent than 27
      hydroxycholesterol. The IC(50) of 24(S)-hydroxycholesterol for inhibiting Abeta
      secretion was approximately 1 nm. Both oxysterols induced ABCA1 expression with
      IC(50) values similar to that for inhibition of A beta secretion, suggesting the
      involvement of liver X receptor. Oxysterols also inhibited protein kinase C
      activity and APP secretion following stimulation of protein kinase C. The
      selective expression of CYP46A1 around neuritic plaques and the potent inhibition
      of APP processing in neurons by 24(S)-hydroxycholesterol suggests that CYP46A1
      affects the pathophysiology of AD and provides insight into how polymorphisms in
      the CYP46A1 gene might influence the pathophysiology of this prevalent disease.

PMID- 15148327
TI  - A gastropod toxin selectively slows early transitions in the Shaker K channel's
      activation pathway.
AB  - A toxin from a marine gastropod's defensive mucus, a disulfide-linked dimer of 6
      bromo-2-mercaptotryptamine (BrMT), was found to inhibit voltage-gated potassium
      channels by a novel mechanism. Voltage-clamp experiments with Shaker K channels
      reveal that externally applied BrMT slows channel opening but not closing. BrMT
      slows K channel activation in a graded fashion: channels activate progressively
      slower as the concentration of BrMT is increased. Analysis of single-channel
      activity indicates that once a channel opens, the unitary conductance and
      bursting behavior are essentially normal in BrMT. Paralleling its effects against
      channel opening, BrMT greatly slows the kinetics of ON, but not OFF, gating
      currents. BrMT was found to slow early activation transitions but not the final
      opening transition of the Shaker ILT mutant, and can be used to pharmacologically
      distinguish early from late gating steps. This novel toxin thus inhibits
      activation of Shaker K channels by specifically slowing early movement of their
      voltage sensors, thereby hindering channel opening. A model of BrMT action is
      developed that suggests BrMT rapidly binds to and stabilizes resting channel
      conformations.

PMID- 15148328
TI  - Incomplete incorporation of tandem subunits in recombinant neuronal nicotinic
      receptors.
AB  - Tandem constructs are increasingly being used to restrict the composition of
      recombinant multimeric channels. It is therefore important to assess not only
      whether such approaches give functional channels, but also whether such channels
      completely incorporate the subunit tandems. We have addressed this question for
      neuronal nicotinic acetylcholine receptors, using a channel mutation as a
      reporter for subunit incorporation. We prepared tandem constructs of nicotinic
      receptors by linking alpha (alpha2-alpha4, alpha6) and beta (beta2, beta4)
      subunits by a short linker of eight glutamine residues. Robust functional
      expression in oocytes was observed for several tandems (beta4_alpha2,
      beta4_alpha3, beta4_alpha4, and beta2_alpha4) when coexpressed with the
      corresponding beta monomer subunit. All tandems expressed when injected alone,
      except for beta4_alpha3, which produced functional channels only together with
      beta4 monomer and was chosen for further characterization. These channels
      produced from beta4_alpha3 tandem constructs plus beta4 monomer were identical
      with receptors expressed from monomer alpha3 and beta4 constructs in
      acetylcholine sensitivity and in the number of alpha and beta subunits
      incorporated in the channel gate. However, separately mutating the beta subunit
      in either the monomer or the tandem revealed that tandem-expressed channels are
      heterogeneous. Only a proportion of these channels contained as expected two
      copies of beta subunits from the tandem and one from the beta monomer construct,
      whereas the rest incorporated two or three beta monomers. Such inaccuracies in
      concatameric receptor assembly would not have been apparent with a standard
      functional characterization of the receptor. Extensive validation is needed for
      tandem-expressed receptors in the nicotinic superfamily.

PMID- 15148329
TI  - ENaC-membrane interactions: regulation of channel activity by membrane order.
AB  - Recently, it was reported that the epithelial Na+ channel (ENaC) is regulated by
      temperature (Askwith, C.C., C.J. Benson, M.J. Welsh, and P.M. Snyder. 2001. Proc.
      Natl. Acad. Sci. USA. 98:6459-6463). As these changes of temperature affect
      membrane lipid order and lipid-protein interactions, we tested the hypothesis
      that ENaC activity can be modulated by membrane lipid interactions. Two
      approaches were used to modulate membrane anisotropy, a lipid order-dependent
      parameter. The nonpharmacological approach used temperature changes, while the
      pharmacological one used chlorpromazine (CPZ), an agent known to decrease
      membrane order, and Gd+3. Experiments used Xenopus oocytes expressing human ENaC.
      Methods of impedance analysis were used to determine whether the effects of
      changing lipid order indirectly altered ENaC conductance via changes of membrane
      area. These data were further corroborated with quantitative morphology on
      micrographs from oocytes membranes studied via electron microscopy. We report
      biphasic effects of cooling (stimulation followed by inhibition) on hENaC
      conductance. These effects were relatively slow (minutes) and were delayed from
      the actual bath temperature changes. Peak stimulation occurred at a calculated
      Tmax of 15.2. At temperatures below Tmax, ENaC conductance was inhibited with
      cooling. The effects of temperature on gNa were distinct from those observed on
      ion channels endogenous to Xenopus oocytes, where the membrane conductance
      decreased monoexponentially with temperature (t = 6.2 degrees C). Similar effects
      were also observed in oocytes with reduced intra- and extracellular [Na+],
      thereby ruling out effects of self or feedback inhibition. Addition of CPZ or the
      mechanosensitive channel blocker, Gd+3, caused inhibition of ENaC. The effects of
      Gd+3 were also attributed to its ability to partition into the outer membrane
      leaflet and to decrease anisotropy. None of the effects of temperature, CPZ, or
      Gd+3 were accompanied by changes of membrane area, indicating the likely absence
      of effects on channel trafficking. However, CPZ and Gd+3 altered membrane
      capacitance in an opposite manner to temperature, consistent with effects on the
      membrane-dielectric properties. The reversible effects of both Gd+3 and CPZ could
      also be blocked by cooling and trapping these agents in the rigidified membrane,
      providing further evidence for their mechanism of action. Our findings
      demonstrate a novel regulatory mechanism of ENaC.

PMID- 15148331
TI  - Human Mannose-binding Lectin in Immunity: Friend, Foe, or Both?
AB  - Human mannose-binding lectin (MBL) recognizes a wide range of microorganisms and
      triggers the most ancient pathway of complement activation. However,
      approximately 5% of individuals lack functional serum MBL and have not been found
      to be prone to severe infections in prospective studies. These data suggest that
      human MBL is largely redundant for protective immunity and may even have been
      subject to counter selection because of a deleterious impact.

PMID- 15148332
TI  - Epstein-barr virus nuclear antigen 1: from immunologically invisible to a
      promising T cell target.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)--the one EBV antigen that is
      expressed in all EBV-associated malignancies--has long been thought to go
      undetected by the cell-mediated immune system. However, recent studies show that
      EBNA1 can be presented to both CD4+ and CD8+ T cells, making it a potential new
      target for immunotherapy of EBV-related cancers.

PMID- 15148333
TI  - Uteroglobin represses allergen-induced inflammatory response by blocking PGD2
      receptor-mediated functions.
AB  - Uteroglobin (UG) is an antiinflammatory protein secreted by the epithelial lining
      of all organs communicating with the external environment. We reported previously
      that UG-knockout mice manifest exaggerated inflammatory response to allergen,
      characterized by increased eotaxin and Th2 cytokine gene expression, and
      eosinophil infiltration in the lungs. In this study, we uncovered that the airway
      epithelia of these mice also express high levels of cyclooxygenase (COX)-2, a key
      enzyme for the production of proinflammatory lipid mediators, and the
      bronchoalveolar lavage fluid (BALF) contain elevated levels of prostaglandin D2.
      These effects are abrogated by recombinant UG treatment. Although it has been
      reported that prostaglandin D2 mediates allergic inflammation via its receptor,
      DP, neither the molecular mechanism(s) of DP signaling nor the mechanism by which
      UG suppresses DP-mediated inflammatory response are clearly understood. Here we
      report that DP signaling is mediated via p38 mitogen-activated protein kinase,
      p44/42 mitogen-activated protein kinase, and protein kinase C pathways in a cell
      type-specific manner leading to nuclear factor-kappaB activation stimulating COX
      2 gene expression. Further, we found that recombinant UG blocks DP-mediated
      nuclear factor-kappaB activation and suppresses COX-2 gene expression. We propose
      that UG is an essential component of a novel innate homeostatic mechanism in the
      mammalian airways to repress allergen-induced inflammatory responses.

PMID- 15148335
TI  - T cell-specific ablation of Fas leads to Fas ligand-mediated lymphocyte depletion
      and inflammatory pulmonary fibrosis.
AB  - To study the role of Fas-Fas ligand (FasL) interaction-mediated apoptosis in
      lymphocyte homeostasis, we generated a mutant fas allele allowing conditional
      inactivation of the fas gene through Cre-mediated recombination. Experiments in
      which Fas was ablated in T cells, B cells, T and B cells, or in a more
      generalized manner demonstrated that the development of lymphoproliferative
      disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and
      nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe
      lymphopenia over time, accompanied by up-regulation of FasL on activated T cells
      and apoptosis of peripheral lymphocytes. In addition, the mutant animals
      developed a fatal wasting syndrome caused by massive leukocyte infiltration in
      the lungs together with increased inflammatory cytokine production and pulmonary
      fibrosis. Inhibition of Fas-FasL interaction in vivo completely prevented the
      loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL
      mediated interaction of activated, Fas-deficient T cells with Fas-expressing
      cells in their environment leads to break down of lymphocyte homeostasis and
      development of a lung disease strikingly resembling idiopathic pulmonary fibrosis
      in humans, a common and severe disease for which the mutant mice may serve as a
      first animal model.

PMID- 15148334
TI  - Inflammation-associated cell cycle-independent block of apoptosis by survivin in
      terminally differentiated neutrophils.
AB  - Survivin has received great attention due to its expression in many human tumors
      and its potential as a therapeutic target in cancer. Survivin expression has been
      described to be cell cycle-dependent and restricted to the G2-M checkpoint, where
      it inhibits apoptosis in proliferating cells. In agreement with this current
      view, we found that survivin expression was high in immature neutrophils, which
      proliferate during differentiation. In contrast with immature cells, mature
      neutrophils contained only little or no survivin protein. Strikingly, these cells
      reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF)
      or granulocyte CSF stimulation in vitro and under inflammatory conditions in
      vivo. Moreover, survivin-deficient mature neutrophils were unable to increase
      their lifespan after survival factor exposure. Together, our findings demonstrate
      the following: (a) overexpression of survivin occurs in primary, even terminally
      differentiated cells and is not restricted to proliferating cells; and (b)
      survivin acts as an inhibitor of apoptosis protein in a cell cycle-independent
      manner. Therefore, survivin plays distinct and independent roles in the
      maintenance of the G2-M checkpoint and in apoptosis control, and its
      overexpression is not restricted to proliferating cells. These data provide new
      insights into the regulation and function of survivin and have important
      implications for the pathogenesis, diagnosis, and treatment of inflammatory
      diseases and cancer.

PMID- 15148336
TI  - Mannose-binding lectin-deficient mice are susceptible to infection with
      Staphylococcus aureus.
AB  - Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity
      and mortality worldwide. Humoral response molecules together with phagocytes play
      a role in host responses to S. aureus. The mannose-binding lectin (MBL, also
      known as mannose-binding protein) is an oligomeric serum molecule that recognizes
      carbohydrates decorating a broad range of infectious agents including S. aureus.
      Circumstantial evidence in vitro and in vivo suggests that MBL plays a key role
      in first line host defense. We tested this contention directly in vivo by
      generating mice that were devoid of all MBL activity. We found that 100% of MBL
      null mice died 48 h after exposure to an intravenous inoculation of S. aureus
      compared with 45% mortality in wild-type mice. Furthermore, we demonstrated that
      neutrophils and MBL are required to limit intraperitoneal infection with S.
      aureus. Our study provides direct evidence that MBL plays a key role in
      restricting the complications associated with S. aureus infection in mice and
      raises the idea that the MBL gene may act as a disease susceptibility gene
      against staphylococci infections in humans.

PMID- 15148337
TI  - A population-based study of morbidity and mortality in mannose-binding lectin
      deficiency.
AB  - Reduced levels of wild-type mannose-binding lectin (MBL) may increase
      susceptibility for infection, other common diseases, and death. We investigated
      associations between MBL deficiency and risk of infection, other common diseases,
      and death during 24, 24, and 8 yr of follow-up, respectively. We genotyped 9,245
      individuals from the adult Danish population for three MBL deficiency alleles, B,
      C, and D, as opposed to the normal noncarrier A allele. Hospitalization incidence
      per 10,000 person. yr was 644 in noncarriers compared with 631 in heterozygotes
      (log-rank: P = 0.39) and 658 in deficiency homozygotes (P = 0.53). Death
      incidence per 10,000 person. yr was 235 in noncarriers compared with 244 in
      heterozygotes (P = 0.44) and 274 in deficiency homozygotes (P = 0.12). After
      stratification by specific cause of hospitalization or death, only
      hospitalization from cardiovascular disorders was increased in deficiency
      homozygotes versus noncarriers (P = 0.02). When retested in two case control
      studies, this association could not be confirmed. Incidence of hospitalization or
      death from infections or other serious common disorders did not differ between
      deficiency homozygotes and noncarriers. In conclusion, in this large study in an
      ethnically homogeneous Caucasian population, there was no evidence for
      significant differences in infectious disease or mortality in MBL-deficient
      individuals versus controls. Our results suggest that MBL deficiency is not a
      major risk factor for morbidity or death in the adult Caucasian population.

PMID- 15148338
TI  - In vivo instruction of suppressor commitment in naive T cells.
AB  - The induction of antigen-specific tolerance in the mature immune system of the
      intact organism has met with limited success. Therefore, nonspecific
      immunosuppression has been the treatment of choice to prevent unwanted immunity.
      Here, it is shown that prolonged subcutaneous infusion of low doses of peptide by
      means of osmotic pumps transforms mature T cells into CD4+25+ suppressor cells
      that can persist for long periods of time in the absence of antigen and confer
      specific immunologic tolerance upon challenge with antigen. The described
      procedure resembles approaches of tolerance induction used decades ago, induces
      tolerance in the absence of immunity, and holds the promise to become an
      effective means of inducing antigen-specific tolerance prospectively, whereas its
      power to suppress already ongoing immune responses remains to be determined.

PMID- 15148339
TI  - CD8 T cell recognition of endogenously expressed epstein-barr virus nuclear
      antigen 1.
AB  - The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine
      repeat (GAr) domain that appears to protect the antigen from proteasomal
      breakdown and, as measured in cytotoxicity assays, from major histocompatibility
      complex (MHC) class I-restricted presentation to CD8+ T cells. This led to the
      concept of EBNA1 as an immunologically silent protein that although unique in
      being expressed in all EBV malignancies, could not be exploited as a CD8 target.
      Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream
      of the GAr domain and assaying recognition by interferon gamma release, we show
      that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines
      (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter
      dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although
      slightly lower than seen with paired lines expressing a GAr-deleted EBNA1
      protein, leads to strong and specific inhibition of LCL outgrowth in vitro.
      Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway
      despite GAr-mediated stabilization of the mature protein. We infer that EBNA1
      specific CD8+ T cells do play a role in control of EBV infection in vivo and
      might be exploitable in the control of EBV+ malignancies.

PMID- 15148340
TI  - Endogenous presentation of CD8+ T cell epitopes from Epstein-Barr virus-encoded
      nuclear antigen 1.
AB  - Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA)1 is thought to escape
      cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of
      synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat
      (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type-dependent
      stability. However, these different degradation rates do not correspond to the
      level of major histocompatibility complex class I-restricted presentation of
      EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL
      epitopes derived from this protein are efficiently processed and presented to
      CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate
      EBNA1-specific memory T cell responses from healthy virus carriers. Functional
      assays revealed that processing of these EBNA1 epitopes is proteasome and
      transporter associated with antigen processing dependent. We also show that the
      endogenous presentation of these epitopes is dependent on the newly synthesized
      protein rather than the long-lived stable EBNA1. Based on these observations, we
      propose that defective ribosomal products, not the full-length antigen, are the
      primary source of endogenously processed CD8+ T cell epitopes from EBNA1.

PMID- 15148341
TI  - Telomere erosion in memory T cells induced by telomerase inhibition at the site
      of antigenic challenge in vivo.
AB  - The extent of human memory T cell proliferation, differentiation, and telomere
      erosion that occurs after a single episode of immune challenge in vivo is
      unclear. To investigate this, we injected tuberculin purified protein derivative
      (PPD) into the skin of immune individuals and isolated responsive T cells from
      the site of antigenic challenge at different times. PPD-specific CD4+ T cells
      proliferated and differentiated extensively in the skin during this secondary
      response. Furthermore, significant telomere erosion occurred in specific T cells
      that respond in the skin, but not in those that are found in the blood from the
      same individuals. Tissue fluid obtained from the site of PPD challenge in the
      skin inhibited the induction of the enzyme telomerase in T cells in vitro.
      Antibody inhibition studies indicated that type I interferon (IFN), which was
      identified at high levels in the tissue fluid and by immunohistology, was
      responsible in part for the telomerase inhibition. Furthermore, the addition of
      IFN-alpha to PPD-stimulated CD4+ T cells directly inhibited telomerase activity
      in vitro. Therefore, these results suggest that the rate of telomere erosion in
      proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN
      during a secondary response in vivo.

PMID- 15148342
TI  - Allelic imbalance analysis by high-density single-nucleotide polymorphic allele
      (SNP) array with whole genome amplified DNA.
AB  - Besides their use in mRNA expression profiling, oligonucleotide microarrays have
      also been applied to single-nucleotide polymorphism (SNP) and loss of
      heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate
      the reliability of using whole genome amplified DNA for analysis with an
      oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and
      chromosomal copy number abnormalities. Whole genome SNP analyses were performed
      with DNA extracted from osteosarcoma tissues and patient-matched blood. SNP calls
      were then generated by Affymetrix GeneChip DNA Analysis Software. In two
      osteosarcoma cases, using unamplified DNA, we identified 793 and 1070 SNP loci
      with allelic imbalance, respectively. In a parallel experiment with amplified
      DNA, 78% and 83% of these SNP loci with allelic imbalance was detected. The
      average false-positive rate is 13.8%. Furthermore, using the Affymetrix GeneChip
      Chromosome Copy Number Tool to analyze the SNP array data, we were able to detect
      identical chromosomal regions with gain or loss in both amplified and unamplified
      DNA at cytoband resolution.

PMID- 15148344
TI  - Analysis of signal-dependent changes in the proteome of Drosophila blood cells
      during an immune response.
AB  - Innate immunity is based on the recognition of cell-surface molecules of
      infecting agents. Microbial substances, such as peptidoglycan,
      lipopolysaccharide, and beta-1,3-glucans, produce functional responses in
      Drosophila hemocytes that contribute to innate immunity. We have used two
      dimensional gel electrophoresis and MS to resolve lipopolysaccharide-induced
      changes in the protein profile of a Drosophila hemocytic cell line. We identified
      24 intracellular proteins that were up- or down-regulated, or modified, in
      response to immune challenge. Several proteins with predicted immune functions,
      including lysosomal proteases, actin-binding/remodeling proteins, as well as
      proteins involved in cellular responses to oxidative stress, were affected by the
      immune assault. Intriguingly, a number of the proteins identified in this study
      have recently been implicated in phagocytosis in higher vertebrates. We suggest
      that phagocytosis is activated in Drosophila hemocytes by the presence of
      microbial substances, and that this activation constitutes an evolutionarily
      conserved arm of innate immunity. In addition, a number of proteins involved in
      calcium-regulated signaling, mRNA processing, and nuclear transport were
      affected, consistent with a possible role in reprogramming of gene expression. In
      conclusion, the present proteome analysis identified many proteins previously not
      linked to innate immunity, demonstrating that differential protein profiling of
      Drosophila hemocytes is a valuable tool for identification of new players in
      immune-related cellular processes.

PMID- 15148343
TI  - An on-chip thin film photodetector for the quantification of DNA probes and
      targets in microarrays.
AB  - A flat microdevice which incorporates a thin-film amorphous silicon (a-Si:H)
      photodetector with an upper layer of functionalized SiO2 is used to quantify the
      density of both immobilized and hybridized DNA oligonucleotides labeled with a
      fluorophore. The device is based on the photoconductivity of hydrogenated
      amorphous silicon in a coplanar electrode configuration. Excitation, with near
      UV/blue light, of a single-stranded DNA molecule tagged with the fluorophore 1-(3
      (succinimidyloxycarbonyl)benzyl)-4-(5-(4-methoxyphenyl)oxazol-2-yl) pyridinium
      bromide (PyMPO), results in the emission of visible light. The emitted light is
      then converted into an electrical signal in the photodetector, thus allowing the
      optoelectronic detection of the DNA molecules. The detection limit of the present
      device is of the order of 1 x 10(12) molecules/cm2 and is limited by the
      efficiency of the filtering of the excitation light. A surface density of 33.5 +/
      4.0 pmol/cm2 was measured for DNA covalently immobilized to the functionalized
      SiO2 thin film and a surface density of 3.7 +/- 1.5 pmol/cm2 was measured for the
      complementary DNA hybridized to the bound DNA. The detection concept explored can
      enable on-chip electronic data acquisition, improving both the speed and the
      reliability of DNA microarrays.

PMID- 15148345
TI  - Cyclooxygenases 1, 2, and 3 and the production of prostaglandin I2: investigating
      the activities of acetaminophen and cyclooxygenase-2-selective inhibitors in rat
      tissues.
AB  - It has been suggested recently that cyclooxygenase-3, formed as a splice variant
      of cyclooxygenase-1, is the enzymatic target for acetaminophen. To investigate
      the relative roles of the putative three cyclooxygenase isoforms in different
      target tissues, we compared the inhibitory effects of acetaminophen, a
      cyclooxygenase-2-selective inhibitor; rofecoxib, a nonsteroid anti-inflammatory
      drug; naproxen; and a cyclooxygenase-1-selective inhibitor, SC560 [5-(4
      chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole]. Prostanoid
      production by aorta, heart, lung, and whole blood was inhibited by all drugs
      tested with the order of potency SC560 > naproxen > acetaminophen >/= rofecoxib.
      In brain and cerebellum, no differences among drug potencies were found. Reverse
      transcription-polymerase chain reaction analysis of aorta, brain, cerebellum,
      heart, and lung showed general expression of cyclooxygenase-1 and cyclooxygenase
      3 mRNA and particular expression of cyclooxygenase-2 mRNA in brain and
      cerebellum. Western blotting demonstrated general expression of cyclooxygenase-1
      in test tissues and cyclooxygenase-2 within the brain and cerebellum. Western
      blotting using a commercially available antibody raised against canine
      cyclooxygenase-3 failed to detect any immunoreactive proteins. In conclusion, our
      studies indicate that cyclooxygenase-1 and cyclooxygenase-2 are the functional
      forms of the enzyme present in the rat tissues tested and that acetaminophen is
      not a selective inhibitor of "cyclooxygenase" activities in the central nervous
      system. This is consistent with the apparent impossibility for the expression of
      cyclooxygenase active protein from cyclooxygenase-3 mRNA in the rat. Also, our
      experiments show that the ability of rofecoxib to depress the circulating levels
      of prostaglandin I(2) is more readily associated with its ability to reduce
      production from the lung, heart, or brain than from arterial vessels.

PMID- 15148346
TI  - Regulation of gene expression in cardiomyocytes by thyroid hormone and thyroid
      hormone analogs 3,5-diiodothyropropionic acid and CGS 23425 [N-[3,5-dimethyl-4
      (4'-hydroxy-3'-isopropylphenoxy)-phenyl]-oxamic acid].
AB  - The heart is an important target of thyroid hormone actions. Only a limited
      number of cardiac target genes have been identified, and little is known about
      their regulation by T(3) (3,3',5-triiodothyronine) and thyroid hormone analogs.
      We used an oligonucleotide microarray to identify novel cardiac genes regulated
      by T(3) and two thyroid hormone analogs, 3,5-diidodothyropropionic acid (DITPA)
      and CGS 23425 [N-[3,5-dimethyl-4-(4'-hydroxy-3'-isopropylphenoxy)-phenyl]-oxamic
      acid]. DITPA binds with lower affinity than T(3) to thyroid hormone receptor
      alpha1 and beta1 isoforms, whereas CGS 23425 binds selectively to beta1.
      Fluorescent-labeled cDNA was prepared from cultured heart cells maintained in
      medium stripped of thyroid hormone ("hypothyroid" control) or treated with T(3),
      DITPA, and CGS 23425 at concentrations 5 times their respective K(d) values for
      48 h. The arrays were scanned and analyzed using an analysis of variance program.
      Sixty-four genes were identified that were >1.5 times up- or down-regulated by
      one of the treatments with P < 0.05. The genes regulated by T(3) and DITPA were
      nearly identical. Thirteen genes were differentially regulated by CGS 23425.
      Genes encoding contractile proteins, Ca(2+)-ATPase of sarcoplasmic reticulum and
      several proteins of mitochondrial oxidative phosphorylation, were up-regulated by
      T(3) and DITPA but not by CGS 23425. These results indicate that some, but not
      all, of the actions of thyroid hormone analogs can be explained by differences in
      gene activation.

PMID- 15148347
TI  - Review: psychosocial issues in pediatric inflammatory bowel disease.
AB  - OBJECTIVE: To review and critically evaluate research on psychosocial issues in
      pediatric inflammatory bowel disease (IBD) and to provide recommendations for
      future research. METHODS: A literature search was conducted using the Medline and
      PsychInfo computerized databases as well as the bibliographies of relevant
      articles. RESULTS: Most of the existing research has compared children with IBD
      to healthy populations and other illness populations. Compared to healthy
      children, children with IBD may be at greater risk for difficulties in behavioral
      and emotional functioning as well as in family and parent functioning, but all
      such functioning appears similar to that found in other illness populations. It
      is unclear if the increased risk reaches clinical significance and what role the
      severity of the disease plays in adjustment. CONCLUSIONS: Future research should
      use a developmental perspective to investigate the process of adaptation to IBD,
      risk factors of poor adjustment, and the role of psychosocial factors in health
      outcomes in pediatric IBD.

PMID- 15148349
TI  - Commentary: computer-based interventions in pediatric psychology.

PMID- 15148348
TI  - Controlled evaluation of the STARBRIGHT CD-ROM program for children and
      adolescents with Cystic Fibrosis.
AB  - OBJECTIVE: To evaluate the effectiveness of the STARBRIGHT Fitting Cystic
      Fibrosis Into Your Life Everyday CD-ROM. Data were analyzed to evaluate the
      effectiveness of the program as an educational tool for children and adolescents
      with cystic fibrosis (CF). METHODS: Forty-seven children and adolescents with CF
      between the ages of 7 and 17 years were enrolled in the study. Participants
      completed an initial evaluation of CF-related knowledge and coping skills and
      were then randomly assigned to one of two groups: the treatment group or the wait
      list control group. Participants then viewed the CD-ROM, and researchers
      completed posttest measures. RESULTS: Analyses indicated that both disease
      related knowledge and coping strategies generated by children and adolescents
      with CF improved as a result of the intervention and that this effect was
      replicated in the wait-list group. CONCLUSIONS: In sum, the results of the
      current study indicate that the STARBRIGHT CD-ROM program is a promising
      intervention for increasing CF-related knowledge and the competence of children's
      and adolescents' coping strategies. These positive results are enhanced by the
      brief, inexpensive, and portable nature of this educational program.

PMID- 15148350
TI  - Childhood unintentional injuries: factors predicting injury risk among
      preschoolers.
AB  - OBJECTIVE: To examine the relationships between maternal perceptions of risk,
      stress, social support, safety-proofing behaviors, supervision practices and
      unintentional injuries to children under 5 years old. METHODS: Household
      interviews were conducted with 159 mothers who had a preschool-age child. The
      secondary data were part of a population-based study that collected self-report
      data and home observational data. Diaries were used for collecting prospective
      injury data. RESULTS: White children whose mothers were unemployed and whose
      homes needed repair were reported to be at higher injury risk than other
      children. Predicting a higher injury risk were children's behavioral
      characteristics as well as their being older than 2.5 years. Maternal social
      support, stress, and coping variables were not related to injury risk. Maternal
      perceptions of risk variables interacted with maternal safety behavior variables
      when predicting injury risk. CONCLUSIONS: Childhood injuries are predicted by a
      set of interrelated sociodemographic, cognitive, behavioral, and child-related
      factors.

PMID- 15148351
TI  - Mothers' home-safety practices for preventing six types of childhood injuries:
      what do they do, and why?
AB  - OBJECTIVE: To identify determinants of mothers' home-safety practices for
      preventing six types of common injuries to children (burns, poisoning, drowning,
      cuts, strangulation/suffocation/choking, and falls). METHODS: Home interviews
      were conducted with mothers of children 19-24 and 25-30 months old about home
      safety practices. For each of 30 safety precautions to prevent these six types of
      injuries, mothers indicated whether or not they engaged in the practice, and
      explained why. RESULTS: Regression analyses revealed both common and unique
      determinants of mothers' home-safety practices to prevent these six types of home
      injuries. For burns, cuts, and falls, beliefs that child characteristics and
      parent characteristics elevated the child's risk of injury were the key
      determinants of the mother's engaging in precautionary measures. For drowning,
      poisoning, and suffocation/strangulation/choking, health beliefs also contributed
      to predict mothers' practices, including beliefs about potential injury severity
      and extent of effort required to implement precautionary measures. CONCLUSIONS:
      The factors that motivated mothers to engage in precautionary measures at home
      varied depending on the type of injury. Intervention programs to enhance maternal
      home-safety practices will need to target different factors depending on the type
      of injury to be addressed.

PMID- 15148352
TI  - Team sport participation and smoking: analysis with general growth mixture
      modeling.
AB  - OBJECTIVE: To assess the likelihood of smoking among adolescents with different
      patterns of team sport participation, grades 9-11. METHODS: Adolescents (N =
      1098) participating in a longitudinal study of the biobehavioral predictors of
      smoking adoption completed items assessing various health-related behaviors,
      including team sport participation and smoking practices. General growth mixture
      modeling (GGMM) was used to analyze the data. RESULTS: Four patterns of team
      sport participation were found. Adolescents with decreasing or erratic
      participation were nearly three times more likely than adolescents with high
      participation to be current smokers in eleventh grade. Nonwhites were at
      particular risk for decreasing and erratic patterns of participation, and later
      smoking. Females were at high risk for low team participation. CONCLUSION:
      Results suggest that multiple patterns of team sport participation can be
      identified with GGMM and that these patterns may be useful in characterizing
      individuals at particular risk for future smoking.

PMID- 15148353
TI  - Brief report: empathy and psychological adjustment in siblings of children with
      cancer.
AB  - OBJECTIVE: To examine relationships between empathy, illness concepts, sibling
      relationship variables, and psychological adjustment among siblings of children
      with cancer. METHODS: Participants were 29 siblings and 14 children diagnosed
      with acute lymphoblastic leukemia, acute myelocytic leukemia, or non-Hodgkin's
      lymphoma. Data included self- and parent-report questionnaires completed during
      active treatment. RESULTS: Siblings did not exhibit increased rates of behavior
      problems, but did display more social and academic difficulties. Empathy was a
      significant predictor of externalizing and total problems. Cancer knowledge was
      not related to adjustment, but was associated with empathy. Birth order of the
      child with cancer and closeness within the sibling relationship were associated
      with less positive adjustment. CONCLUSIONS: Empathy may play an important role in
      sibling adjustment following the diagnosis of cancer. Specific sibling
      relationship and family variables may be helpful in identifying siblings who are
      at greater need for psychosocial intervention.

PMID- 15148354
TI  - Brief report: parent perspectives of nutritional status and mealtime behaviors in
      children with sickle cell disease.
AB  - OBJECTIVE: To qualitatively evaluate parent perspectives of eating problems,
      nutritional status, and the potential for nutritional intervention in children
      with sickle cell disease (SCD). METHODS: Twenty parents of children with SCD
      participated in one of three focus groups to discuss questions related to the
      study's objectives. Three coders rated transcripts to identify common perceptions
      and experiences (themes) among participants. RESULTS: Poor appetite and its
      impact on nutritional and general health were particular concerns for parents.
      Parents addressed eating challenges with dietary supplementation, limit setting,
      and compromising at meals, often without consultation from health professionals.
      An intervention program should include facilitators, such as flexible scheduling
      and incentives to counter barriers, such as scheduling and child care conflicts.
      CONCLUSIONS: Parents of children with SCD reported a range of eating behavior
      challenges. Parents presented ideas on how nutritional intervention could be
      culturally sensitive and on how to promote participation in such programs.

PMID- 15148356
TI  - Gene mining: a novel and powerful ensemble decision approach to hunting for
      disease genes using microarray expression profiling.
AB  - Current applications of microarrays focus on precise classification or discovery
      of biological types, for example tumor versus normal phenotypes in cancer
      research. Several challenging scientific tasks in the post-genomic epoch, like
      hunting for the genes underlying complex diseases from genome-wide gene
      expression profiles and thereby building the corresponding gene networks, are
      largely overlooked because of the lack of an efficient analysis approach. We have
      thus developed an innovative ensemble decision approach, which can efficiently
      perform multiple gene mining tasks. An application of this approach to analyze
      two publicly available data sets (colon data and leukemia data) identified 20
      highly significant colon cancer genes and 23 highly significant molecular
      signatures for refining the acute leukemia phenotype, most of which have been
      verified either by biological experiments or by alternative analysis approaches.
      Furthermore, the globally optimal gene subsets identified by the novel approach
      have so far achieved the highest accuracy for classification of colon cancer
      tissue types. Establishment of this analysis strategy has offered the promise of
      advancing microarray technology as a means of deciphering the involved genetic
      complexities of complex diseases.

PMID- 15148355
TI  - Enhanced fidelity for rejoining radiation-induced DNA double-strand breaks in the
      G2 phase of Chinese hamster ovary cells.
AB  - The influence of cell cycle phase on the fidelity of DNA double-strand break
      (DSB) repair is largely unknown. We investigated the rejoining of correct and
      incorrect DSB ends in synchronized populations of Chinese hamster ovary cells
      irradiated with 80 Gy X-rays. A specialized pulsed-field gel electrophoresis
      assay based on quantitative Southern hybridization of individual large
      restriction fragments was employed to measure correct DSB rejoining by monitoring
      restriction fragment reconstitution. Total DSB repair, representing both correct
      and incorrect rejoining, was analyzed using conventional pulsed-field gel
      electrophoresis. We present evidence that restriction fragment reconstitution is
      more efficient in G2 than in G1, suggesting that DSB rejoining in G2 proceeds
      with higher fidelity. DNA-dependent protein kinase-deficient V3 and xrs-6 cells
      show impaired restriction fragment reconstitution in G1 and G2 compared with wild
      type AA8 and K1 cells, demonstrating that the enhanced fidelity of DSB rejoining
      in G2 occurs by non- homologous end joining. Additionally, homologous
      recombination-deficient irs1SF and wild-type cells show identical DSB rejoining
      in G1 and G2. We propose that structural characteristics of G2 phase chromatin,
      such as the cohesion of sister chromatids in replicated chromatin, limit the
      mobility of radiation-induced break ends and enhance the fidelity of DSB
      rejoining.

PMID- 15148357
TI  - Identification and functional validation of PNAs that inhibit murine CD40
      expression by redirection of splicing.
AB  - Cognate recognition between the CD40 receptor and its ligand, CD154, is thought
      to play a central role in the initiation and propagation of immune responses. We
      describe the specific down regulation of cell surface associated CD40 protein
      expression by use of a peptide nucleic acid (PNA) antisense inhibitor, ISIS
      208529, that is designed to bind to the 3' end of the exon 6 splice junction
      within the primary CD40 transcript. Binding of ISIS 208529 was found to alter
      constitutive splicing, leading to the accumulation of a transcript lacking exon
      6. The resulting protein product lacks the transmembrane domain. ISIS 208529
      mediated CD40 protein depletion was found to be sequence specific and dose
      dependent, and was dependent on the length of the PNA oligomer. CD40-dependent
      induction of IL-12 in primary murine macrophages was attenuated in cells treated
      with ISIS 208529. Oligolysine conjugation to the PNA inhibitor produced an
      inhibitor, ISIS 278647, which maintained its specificity and displayed efficacy
      in BCL1 cells and in primary murine macrophages in the absence of delivery
      agents. These results demonstrate that PNA oligomers can be effective inhibitors
      of CD40 expression and hence may be useful as novel immuno-modulatory agents.

PMID- 15148358
TI  - A three-fluorophore FRET assay for high-throughput screening of small-molecule
      inhibitors of ribosome assembly.
AB  - In one of the first steps of prokaryotic ribosome assembly, the ribosomal protein
      S15 binds to a three-way junction in the central domain of the 16S rRNA. Binding
      causes a conformational change that is required for subsequent binding events.
      Using a novel fluorescence resonance energy transfer assay with three
      fluorophores, two on the RNA and one on the S15 protein, small-molecule libraries
      can be screened for potential inhibitors of this initial step in ribosome
      assembly. The employment of three fluorophores allows both the conformational
      change of the RNA and the binding of S15 to be monitored in a single assay.

PMID- 15148360
TI  - Gene delivery by dendrimers operates via a cholesterol dependent pathway.
AB  - Understanding the cellular uptake and intracellular trafficking of dendrimer-DNA
      complexes is an important prerequisite for improving the transfection efficiency
      of non-viral vector-mediated gene delivery. Dendrimers are synthetic polymers
      used for gene transfer. Although these cationic molecules show promise as
      versatile DNA carriers, very little is known about the mechanism of gene
      delivery. This paper investigates how the uptake occurs, using an endothelial
      cell line as model, and evaluates whether the internalization of dendriplexes
      takes place randomly on the cell surface or at preferential sites such as
      membrane rafts. Following extraction of plasma membrane cholesterol, the
      transfection efficiency of the gene delivered by dendrimers was drastically
      decreased. Replenishment of membrane cholesterol restored the gene expression.
      The binding and especially internalization of dendriplexes was strongly reduced
      by cholesterol depletion before transfection. However, cholesterol removal after
      transfection did not inhibit expression of the delivered gene. Fluorescent
      dendriplexes co-localize with the ganglioside GM1 present into membrane rafts in
      both an immunoprecipitation assay and confocal microscopy studies. These data
      strongly suggest that membrane cholesterol and raft integrity are physiologically
      relevant for the cellular uptake of dendrimer-DNA complexes. Hence these findings
      provide evidence that membrane rafts are important for the internalization of non
      viral vectors in gene therapy.

PMID- 15148359
TI  - Isolation and characterization of a novel DNA methyltransferase complex linking
      DNMT3B with components of the mitotic chromosome condensation machinery.
AB  - Proper patterns of genome-wide DNA methylation, mediated by DNA
      methyltransferases DNMT1, -3A and -3B, are essential for embryonic development
      and genomic stability in mammalian cells. The de novo DNA methyltransferase
      DNMT3B is of particular interest because it is frequently overexpressed in tumor
      cells and is mutated in immunodeficiency, centromere instability and facial
      anomalies (ICF) syndrome. In order to gain a better understanding of DNMT3B, in
      terms of the targeting of its methylation activity and its role in genome
      stability, we biochemically purified endogenous DNMT3B from HeLa cells. DNMT3B co
      purifies and interacts, both in vivo and in vitro, with several components of the
      condensin complex (hCAP-C, hCAP-E and hCAP-G) and KIF4A. Condensin mediates
      genome-wide chromosome condensation at the onset of mitosis and is critical for
      proper segregation of sister chromatids. KIF4A is proposed to be a motor protein
      carrying DNA as cargo. DNMT3B also interacts with histone deacetylase 1 (HDAC1),
      the co-repressor SIN3A and the ATP-dependent chromatin remodeling enzyme hSNF2H.
      Further more, DNMT3B co-localizes with condensin and KIF4A on condensed
      chromosomes throughout mitosis. These studies therefore reveal the first direct
      link between the machineries regulating DNA methylation and mitotic chromosome
      condensation in mammalian cells.

PMID- 15148361
TI  - Comprehensive search for HNF-1beta-regulated genes in mouse hepatoma cells
      perturbed by transcription regulatory factor-targeted RNAi.
AB  - The identification of genes targeted by a specific transcription regulatory
      factor (TRF) is essential to our understanding of the regulatory mechanism of
      gene expression. We constructed a system for the comprehensive identification of
      genes directly regulated by a TRF. It includes a combination of perturbation of
      gene expression by RNA interference (RNAi) of the TRF, cDNA microarray analysis,
      computer searches for the putative TRF recognition sequences, and in vivo and in
      vitro TRF-DNA binding assays. Endogenous hepatocyte nuclear factor-1beta (HNF
      1beta) mRNA was efficiently degraded by transfection of mouse hepatoma cells with
      short interfering RNAs. Expression profile analysis with 20 K mouse cDNA
      microarrays detected 243 genes whose expression levels were decreased by >50%
      upon RNAi of HNF-1beta. The upstream regions of the top 26 downregulated genes
      were searched for the HNF-1beta consensus recognition sequences leading to the
      extraction of 13 candidate genes. Finally, TRF-DNA binding assays identified five
      novel as well as three known HNF-1beta-regulated genes. In combination with
      quantitative real-time RT-PCR, the present system revealed the existence of a
      more expanded regulatory network among seven HNF family members, demonstrating
      its practicability to identify the TRF network as well as genes directly
      regulated by a specific TRF.

PMID- 15148362
TI  - CsdA, a cold-shock RNA helicase from Escherichia coli, is involved in the
      biogenesis of 50S ribosomal subunit.
AB  - CsdA, a DEAD-box protein from Escherichia coli, has been proposed to participate
      in a variety of processes, such as translation initiation, gene regulation after
      cold-shock, mRNA decay and biogenesis of the small ribosomal subunit. Whether the
      protein really plays a direct role in these multiple processes is however, not
      clear. Here, we show that CsdA is involved in the biogenesis of the large rather
      than the small ribosomal subunit. Deletion of the csdA gene leads to a deficit in
      free 50S subunits at low temperatures and to the accumulation of a new particle
      sedimenting around 40S. Analysis of the RNA and protein contents of this particle
      indicates that it corresponds to a mis-assembled large subunit. Sucrose gradient
      fractionation shows that in wild-type cells CsdA associates mainly with a pre50S
      particle. Presumably the RNA helicase activity of CsdA permits a structural
      rearrangement during 50S biogenesis at low temperature. We showed previously that
      SrmB, another DEAD-box RNA helicase, is also involved in 50S assembly in E.coli.
      Our results suggest that CsdA is required at a later step than SrmB. However,
      over-expression of CsdA corrects the ribosome defect of the srmB-deleted strain,
      indicating that some functional overlap exists between the two proteins.

PMID- 15148363
TI  - Design of temperature-sensitive mutants solely from amino acid sequence.
AB  - Temperature-sensitive (Ts) mutants are a powerful tool with which to study gene
      function in vivo. Ts mutants are typically generated by random mutagenesis
      followed by laborious screening procedures. By using the Escherichia coli
      cytotoxin CcdB as a model system, simple procedures for generating Ts mutants at
      high frequency through site-directed mutagenesis were developed. Putative buried,
      hydrophobic residues are selected through analysis of the protein sequence.
      Residue burial is confirmed by ensuring that substitution of the residue by Asp
      leads to protein inactivation. At such sites, a Ts phenotype can typically be
      generated either by (i) substitution of two predicted, buried residues with the
      18 remaining amino acids or (ii) introduction of Lys, Ser, Ala, and Trp at three
      to four predicted buried sites. By using these design strategies, 17 tight Ts
      mutants of CcdB were isolated at four predicted buried sites. The rules were
      further verified by making several Ts mutants of yeast Gal4 at residues 68, 69,
      and 70. No Ts mutants of either protein have been previously reported. Such Ts
      mutants of Gal4 can be used for conditional expression of a variety of genes by
      using the well characterized upstream-activating-sequence-Gal4 system.

PMID- 15148365
TI  - Flint mining in prehistory recorded by in situ-produced cosmogenic 10Be.
AB  - The development of mining to acquire the best raw materials for producing stone
      tools represents a breakthrough in human technological and intellectual
      development. We present a new approach to studying the history of flint mining,
      using in situ-produced cosmogenic 10Be concentrations. We show that the raw
      material used to manufacture flint artifacts approximately 300,000 years old from
      Qesem Cave (Israel) was most likely surface-collected or obtained from shallow
      quarries, whereas artifacts of the same period from Tabun Cave (Israel) were made
      of flint originating from layers 2 or more meters deep, possibly mined or
      quarried by humans.

PMID- 15148364
TI  - Trigger factor binds to ribosome-signal-recognition particle (SRP) complexes and
      is excluded by binding of the SRP receptor.
AB  - Trigger factor (TF) and signal recognition particle (SRP) bind to the bacterial
      ribosome and are both crosslinked to protein L23 at the peptide exit, where they
      interact with emerging nascent peptide chains. It is unclear whether TF and SRP
      exclude one another from their ribosomal binding site(s). Here we show that SRP
      and TF can bind simultaneously to ribosomes or ribosome nascent-chain complexes
      exposing a SRP-specific signal sequence. Based on changes of the crosslinking
      pattern and on results obtained by fluorescence measurements using fluorescence
      labeled SRP, TF binding induces structural changes in the ribosome-SRP complex.
      Furthermore, we show that binding of the SRP receptor, FtsY, to ribosome-bound
      SRP excludes TF from the ribosome. These results suggest that TF and SRP sample
      nascent chains on the ribosome in a nonexclusive fashion. The decision for
      ribosome nascent-chain complexes exposing a signal sequence to enter SRP
      dependent membrane targeting seems to be determined by the binding of SRP, which
      is stabilized by signal sequence recognition, and promoted by the exclusion of TF
      due to the binding of the SRP receptor to ribosome-bound SRP.

PMID- 15148367
TI  - Activity-based probes for protein tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are involved in the regulation of many
      aspects of cellular activity including proliferation, differentiation,
      metabolism, migration, and survival. Given the large number and complexity of
      PTPs in cell signaling, new strategies are needed for the integrated analysis of
      PTPs in the whole proteome. Unfortunately, the activities of many PTPs are
      tightly regulated by posttranslational mechanisms, limiting the utility of
      standard genomics and proteomics methods for functional characterization of these
      enzymes. To facilitate the global analysis of PTPs, we designed and synthesized
      two activity-based probes that consist of alpha-bromobenzylphosphonate as a PTP
      specific trapping device and a linker that connects the trapping device with a
      biotin tag for visualization and purification. We showed that these probes are
      active site-directed irreversible inactivators of PTPs and form a covalent adduct
      with PTPs involving the active site Cys residue. Additionally, we demonstrated
      that the probes are extremely specific toward PTPs while remaining inert to other
      proteins, including the whole proteome from Escherichia coli. Consequently, these
      activity-based PTP probes can be used to profile PTP activity in complex
      proteomes. The ability to interrogate the entire PTP family on the basis of
      changes in their activity should greatly accelerate both the assignment of PTP
      function and the identification of potential therapeutic targets.

PMID- 15148366
TI  - Predicting indirect readout effects in protein-DNA interactions.
AB  - Recognition of DNA by proteins relies on direct interactions with specific DNA
      functional groups, along with indirect effects that reflect variable energetics
      in the response of DNA sequences to twisting and bending distortions induced by
      proteins. Predicting indirect readout requires knowledge of the variations in DNA
      curvature and flexibility in the affected region, which we have determined for a
      series of DNA-binding sites for the E2 regulatory protein by using the
      cyclization kinetics method. We examined 16 sites containing different
      noncontacted spacer sequences, which vary by more than three orders of magnitude
      in binding affinity. For 15 of these sites, the variation in affinity was
      predicted within a factor of 3, by using experimental curvature and flexibility
      values and a statistical mechanical theory. The sole exception was traced to
      differential magnesium ion binding.

PMID- 15148368
TI  - Telomere length is reset during early mammalian embryogenesis.
AB  - The enzyme telomerase is active in germ cells and early embryonic development and
      is crucial for the maintenance of telomere length. Whereas the different length
      of telomeres in germ cells and somatic cells is well documented, information on
      telomere length regulation during embryogenesis is lacking. In this study, we
      demonstrate a telomere elongation program at the transition from morula to
      blastocyst in mice and cattle that establishes a specific telomere length set
      point during embryogenesis. We show that this process restores telomeres in
      cloned embryos derived from fibroblasts, regardless of the telomere length of
      donor nuclei, and that telomere elongation at this stage of embryogenesis is
      telomerase-dependent because it is abrogated in telomerase-deficient mice. These
      data demonstrate that early mammalian embryos have a telomerase-dependent genetic
      program that elongates telomeres to a defined length, possibly required to ensure
      sufficient telomere reserves for species integrity.

PMID- 15148369
TI  - Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a
      regulator of the anaphase promoting complex/cyclosome.
AB  - Early mitotic inhibitor 1 (Emi1) inhibits the activity of the anaphase promoting
      complex/cyclosome (APC/C), which is a multisubunit ubiquitin ligase that targets
      mitotic regulators for degradation in exit from mitosis. Levels of Emi1 oscillate
      in the cell cycle: it accumulates in the S phase and is rapidly degraded in
      prometaphase. The degradation of Emi1 in early mitosis is necessary for the
      activation of APC/C in late mitosis. Previous studies have shown that Emi1 is
      targeted for degradation in mitosis by a Skp1-Cullin1 F-box protein (SCF)
      ubiquitin ligase complex that contains the F-box protein beta-TrCP. As with other
      substrates of SCF(beta-TrCP), the phosphorylation of Emi1 on a DSGxxS sequence is
      required for this process. However, the protein kinase(s) involved has not been
      identified. We find that Polo-like kinase 1 (Plk1), a protein kinase that
      accumulates in mitosis, markedly stimulates the ligation of Emi1 to ubiquitin by
      purified SCF(beta-TrCP). Cdk1-cyclin B, another major mitotic protein kinase, has
      no influence on this process by itself but stimulates the action of Plk1 at low,
      physiological concentrations. Plk1 phosphorylates serine residues in the DSGxxS
      sequence of Emi1, as suggested by the reduced phosphorylation of a derivative in
      which the two serines were mutated to nonphosphorylatable amino acids.
      Transfection with an small interfering RNA duplex directed against Plk1 caused
      the accumulation of Emi1 in mitotically arrested HeLa cells. It is suggested that
      phosphorylation of Emi1 by Plk1 is involved in its degradation in mitosis.

PMID- 15148370
TI  - H5N1 influenza: a protean pandemic threat.
AB  - Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03
      and A/HK/213/03) was fatal to one of two members of a family in southern China in
      2003. This incident was preceded by lethal outbreaks of H5N1 influenza in
      waterfowl, which are the natural hosts of these viruses and, therefore, normally
      have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like
      viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses
      that caused the first known cases of human disease in Hong Kong in 1997, but
      their internal protein genes originated elsewhere. The hemagglutinin of the
      recent human isolates has undergone significant antigenic drift. Like the 1997
      human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of
      proinflammatory cytokines by primary human macrophages in vitro, whereas the
      precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The
      acquisition by the viruses of characteristics that enhance virulence in humans
      and waterfowl and their potential for wider distribution by infected migrating
      birds are causes for renewed pandemic concern.

PMID- 15148371
TI  - Cretaceous flowers of Nymphaeaceae and implications for complex insect entrapment
      pollination mechanisms in early angiosperms.
AB  - Based on recent molecular systematics studies, the water lily lineage
      (Nymphaeales) provides an important key to understanding ancestral angiosperm
      morphology and is of considerable interest in the context of angiosperm origins.
      Therefore, the fossil record of Nymphaeales potentially provides evidence on both
      the timing and nature of diversification of one of the earliest clades of
      flowering plants. Recent fossil evidence of Turonian age (approximately 90
      million years B.P.) includes fossil flowers with characters that, upon rigorous
      analysis, firmly place them within Nymphaeaceae. Unequivocally the oldest floral
      record of the Nymphaeales, these fossils are closely related to the modern
      Nymphaealean genera Victoria (the giant Amazon water lily) and Euryale. Although
      the fossils are much smaller than their modern relatives, the precise and
      dramatic correspondence between the fossil floral morphology and that of modern
      Victoria flowers suggests that beetle entrapment pollination was present in the
      earliest part of the Late Cretaceous.

PMID- 15148372
TI  - Geometry and symmetry presculpt the free-energy landscape of proteins.
AB  - We present a simple physical model that demonstrates that the native-state folds
      of proteins can emerge on the basis of considerations of geometry and symmetry.
      We show that the inherent anisotropy of a chain molecule, the geometrical and
      energetic constraints placed by the hydrogen bonds and sterics, and
      hydrophobicity are sufficient to yield a free-energy landscape with broad minima
      even for a homopolymer. These minima correspond to marginally compact structures
      comprising the menu of folds that proteins choose from to house their native
      states in. Our results provide a general framework for understanding the common
      characteristics of globular proteins.

PMID- 15148374
TI  - Scanning electrochemical microscopy of menadione-glutathione conjugate export
      from yeast cells.
AB  - The uptake of menadione (2-methyl-1,4-naphthoquinone), which is toxic to yeast
      cells, and its expulsion as a glutathione complex were studied by scanning
      electrochemical microscopy. The progression of the in vitro reaction between
      menadione and glutathione was monitored electrochemically by cyclic voltammetry
      and correlated with the spectroscopic (UV-visible) behavior. By observing the
      scanning electrochemical microscope tip current of yeast cells suspended in a
      menadione-containing solution, the export of the conjugate from the cells with
      time could be measured. Similar experiments were performed on immobilized yeast
      cell aggregates stressed by a menadione solution. From the export of the
      menadione-glutathione conjugate detected at a 1-microm-diameter electrode
      situated 10 microm from the cells, a flux of about 30,000 thiodione molecules per
      second per cell was extracted. Numerical simulations based on an explicit finite
      difference method further revealed that the observation of a constant efflux of
      thiodione from the cells suggested the rate was limited by the uptake of
      menadione and that the efflux through the glutathione-conjugate pump was at least
      an order of magnitude faster.

PMID- 15148373
TI  - E-selectin is required for the antiangiogenic activity of endostatin.
AB  - Endostatin, a 20-kDa fragment of collagen XVIII, is a potent angiogenesis
      inhibitor. E-selectin, an inducible leukocyte adhesion molecule specifically
      expressed by endothelial cells, has also been implicated in angiogenesis. By
      using in vivo, ex vivo, and in vitro angiogenic assays, we investigated the
      functional relationship between endostatin and E-selectin. In corneal micropocket
      assays, recombinant endostatin administered i.p. by osmotic pump inhibited basic
      fibroblast growth factor-induced angiogenesis in WT, but not E-selectin
      deficient, mice. Similarly, endostatin inhibited vascular endothelial growth
      factor-stimulated endothelial sprout formation from aortic rings dissected from
      WT but not from E-selectin-deficient mice. To further explore this apparent
      requirement for E-selectin in endostatin action, we manipulated E-selectin
      expression in cultured human endothelial cells. When E-selectin was induced by IL
      1beta, or lipopolysaccharide, human umbilical vein endothelial cells and human
      dermal microvascular endothelial cells each became markedly more sensitive to
      inhibition by endostatin in a vascular endothelial growth factor-induced cell
      migration assay. To dissociate E-selectin expression from other consequences of
      endothelial activation, human umbilical vein endothelial cells were transduced
      with an adenoviral human E-selectin expression construct; these cells also showed
      increased sensitivity to endostatin, and this effect required the E-selectin
      cytoplasmic domain. Taken together, these results indicate that E-selectin is
      required for the antiangiogenic activity of endostatin in vivo and ex vivo and
      confers endostatin sensitivity to nonresponsive human endothelial cells in vitro.
      E-selectin may be a useful predictor and modulator of endostatin efficacy in
      antiangiogenic therapy.

PMID- 15148375
TI  - The minimal promoter plays a major role in silencing of the galago gamma-globin
      gene in adult erythropoiesis.
AB  - The human gamma-globin gene and its orthologous galago gamma-globin gene evolved
      from an ancestral epsilon-globin gene. In galago, expression of the gamma-gene
      remained restricted to the embryonic stage of development, whereas in humans,
      expression of the gamma-gene was recruited to the fetal stage. To localize the
      cis-elements responsible for this developmentally distinct regulation, we studied
      the expression patterns of the human gamma-gene driven by either the human or the
      galago gamma-promoters in transgenic mice. gamma-gene transcription driven by
      either promoter reached similar levels in embryonic erythropoiesis. In adult
      erythropoiesis the gamma-gene was silenced when controlled by the galago gamma
      promoter, but it was expressed at a high level when it was linked to the human
      gamma-promoter. By a series of gamma-promoter truncations the sequences required
      for the down-regulation of the galago gamma-globin gene were localized to the
      minimal promoter. Furthermore, by interchanging the TATA, CCAAT, and CACCC
      elements between the human and galago minimal promoters we found that whereas
      each box made a developmentally distinctive contribution to gamma-globin gene
      expression, the CACCC box was largely responsible for the down-regulation of the
      gamma-gene in adult erythropoiesis.

PMID- 15148376
TI  - Tracking the cryptic pumiliotoxins.

PMID- 15148377
TI  - The dynamic processivity of the T4 DNA polymerase during replication.
AB  - The polymerase (gp43) processivity during T4 replisome mediated DNA replication
      has been investigated. The size of the Okazaki fragments remains constant over a
      wide range of polymerase concentrations. A dissociation rate constant of
      approximately 0.0013 sec(-1) was measured for the polymerases from both strands,
      consistent with highly processive replication on both the leading and lagging
      strands. This processive replication, however, can be disrupted by a
      catalytically inactive mutant D408N gp43 that retains normal affinity for DNA and
      the clamp. The inhibition kinetics fit well to an active exchange model in which
      the mutant polymerase (the polymerase trap) displaces the replicating polymerase.
      This kinetic model was further strengthened by the observation that the sizes of
      both the Okazaki fragments and the extension products on a primed M13mp18
      template were reduced in the presence of the mutant polymerase. The effects of
      the trap polymerase therefore suggest a dynamic processivity of the polymerase
      during replication, namely, a solution/replisome polymerase exchange takes place
      without affecting continued DNA synthesis. This process mimics the polymerase
      switching recently suggested during the translesion DNA synthesis, implies the
      multiple functions of the clamp in replication, and may play a potential role in
      overcoming the replication barriers by the T4 replisome.

PMID- 15148378
TI  - Unique CD40-mediated biological program in B cell activation requires both type 1
      and type 2 NF-kappaB activation pathways.
AB  - B lymphocytes can be activated by many different stimuli. However, the mechanisms
      responsible for the signaling and functional specificities of individual stimuli
      remain to be elucidated. Here, we have compared the contribution of the type 1
      (p50-dependent) and type 2 (p52-dependent) NF-kappaB activation pathways to cell
      survival, proliferation, homotypic aggregation, and specific gene regulation of
      murine primary B lymphocytes. Whereas lipopolysaccharide (LPS) and B cell
      activation factor (BAFF) mainly activate the type 1 or type 2 pathways,
      respectively, CD40 ligand (CD40L) strongly activates both. Rescue of spontaneous
      apoptosis is diminished in p52(-/-) B cells after BAFF stimulation and in p50(-/
      )c-Rel(-/-) B cells after LPS stimulation. Interestingly, significant CD40
      induced B cell survival is still observed even in p50(-/-)c-Rel(-/-)p65(-/+) B
      cells, which is correlated with the ability of CD40L to up-regulate Bcl-x(L)
      expression in these cells. CD40L- and LPS-induced B cell proliferation, as well
      as up-regulation of proliferation-related genes, however, are greatly reduced in
      c-Rel(-/-) and p50(-/-)c-Rel(-/-) B cells but are normal in p52(-/-) B cells. We
      have further demonstrated that both c-Rel and p52 are required for CD40-mediated
      B cell homotypic aggregation, which explains well why neither LPS nor BAFF has
      this function. Overall, our studies suggest that both type 1 and type 2 NF-kappaB
      pathways contribute to the gene expression and biological program unique for CD40
      in B cell activation.

PMID- 15148379
TI  - Quinone biogenesis: Structure and mechanism of PqqC, the final catalyst in the
      production of pyrroloquinoline quinone.
AB  - The biosynthesis of pyrroloquinoline quinone (PQQ), a vitamin and redox cofactor
      of quinoprotein dehydrogenases, is facilitated by an unknown pathway that
      requires the expression of six genes, pqqA to -F. PqqC, the protein encoded by
      pqqC, catalyzes the final step in the pathway in a reaction that involves ring
      cyclization and eight-electron oxidation of 3a-(2-amino-2-carboxyethyl)-4,5-dioxo
      4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic-acid to PQQ. Herein, we describe
      the crystal structures of PqqC and its complex with PQQ and determine the
      stoichiometry of H2O2 formation and O2 uptake during the reaction. The PqqC
      structure(s) reveals a compact seven-helix bundle that provides the scaffold for
      a positively charged active site cavity. Product binding induces a large
      conformational change, which results in the active site recruitment of amino acid
      side chains proposed to play key roles in the catalytic mechanism. PqqC is
      unusual in that it transfers redox equivalents to molecular oxygen without the
      assistance of a redox active metal or cofactor. The structure of the enzyme
      product complex shows additional electron density next to R179 and C5 of PQQ,
      which can be modeled as O2 or H2O2, indicating a site for oxygen binding. We
      propose a reaction sequence that involves base-catalyzed cyclization and a series
      of quinone-quinol tautomerizations that are followed by cycles of O2/H2O2
      mediated oxidations.

PMID- 15148380
TI  - Discovery and characterization of an epithelial-specific galectin in the
      endometrium that forms crystals in the trophectoderm.
AB  - Secretions of the uterus support survival and growth of the conceptus
      (embryo/fetus and associated membranes) during pregnancy. Galectin-15, also known
      as OVGAL11 and a previously uncharacterized member of the galectin family of
      secreted beta-galactoside lectins containing a conserved carbohydrate recognition
      domain and a separate putative integrin binding domain, was discovered in the
      uterus of sheep. In endometria of cyclic and pregnant sheep, galectin-15 mRNA was
      expressed specifically in the endometrial luminal epithelium but not in the
      conceptus. In pregnant sheep, galectin-15 mRNA expression appeared in the
      epithelia between days 10 and 12 and increased between days 12 and 16.
      Progesterone induced and IFN-tau stimulated galectin-15 mRNA in the endometrial
      epithelium. Galectin-15 protein was concentrated near and on the apical surface
      of the endometrial luminal epithelia and localized within discrete cytoplasmic
      crystalline structures of conceptus trophectoderm (Tr). In the uterine lumen,
      secreted galectin-15 protein increased between days 14 and 16 of pregnancy.
      Galectin-15 protein was functional in binding lactose and mannose sugars and
      immunologically identical to the unnamed Mr 14,000 (14K) protein from the ovine
      uterus that forms crystalline inclusion bodies in endometrial epithelia and
      conceptus Tr. Based on the functional studies of other galectins, galectin-15 is
      hypothesized to function extracellularly to regulate Tr migration and adhesion to
      the endometrial epithelium and intracellularly to regulate Tr cell survival,
      growth, and differentiation. Galectins may be useful as cellular and molecular
      markers for endometrial function and receptivity, to enhance conceptus survival
      and development, and to evaluate and enhance fertility.

PMID- 15148381
TI  - Dynamic mapping of human cortical development during childhood through early
      adulthood.
AB  - We report the dynamic anatomical sequence of human cortical gray matter
      development between the age of 4-21 years using quantitative four-dimensional
      maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain
      MRI scans were obtained every 2 years, for 8-10 years, were studied. By using
      models of the cortical surface and sulcal landmarks and a statistical model for
      gray matter density, human cortical development could be visualized across the
      age range in a spatiotemporally detailed time-lapse sequence. The resulting time
      lapse "movies" reveal that (i) higher-order association cortices mature only
      after lower-order somatosensory and visual cortices, the functions of which they
      integrate, are developed, and (ii) phylogenetically older brain areas mature
      earlier than newer ones. Direct comparison with normal cortical development may
      help understanding of some neurodevelopmental disorders such as childhood-onset
      schizophrenia or autism.

PMID- 15148382
TI  - Forebrain degeneration and ventricle enlargement caused by double knockout of
      Alzheimer's presenilin-1 and presenilin-2.
AB  - Early-onset familial Alzheimer's disease is the most aggressive form of
      Alzheimer's, striking patients as early as their 30s; those patients typically
      carry mutations in presenilin-1 and presenilin-2. To investigate the coordinated
      functions of presenilin in the adult brain, we generated double knockout mice, in
      which both presenilins were deleted in the forebrain. We found that concurrent
      loss of presenilins in adulthood resulted in massive cortical shrinkage, atrophy
      of hippocampal molecular layers and corpus callosum, and enlargement of the
      lateral and third ventricles. We further revealed that deficiency of presenilins
      caused a series of biochemical alterations, including neuronal atrophy,
      astrogliosis, caspase-3-mediated apoptosis, and tau hyperphosphorylation. Thus,
      our study demonstrates that presenilins are essential for the ongoing maintenance
      of cortical structures and function.

PMID- 15148383
TI  - Previous-year reproduction reduces photosynthetic capacity and slows lifetime
      growth in females of a neotropical tree.
AB  - Females of dioecious plant species typically invest more in reproduction than
      males because they produce seeds, fruits, and associated structures in addition
      to flowers. If females are unable to compensate by up-regulating rates of
      photosynthesis or by reproducing less frequently than males, their greater
      reproductive investment may result in reduced growth or higher mortality. Here we
      provide evidence of the cost of reproduction in Ocotea tenera (Lauraceae), a
      dioecious neotropical tree common in lower montane forests of Monteverde, Costa
      Rica. Over periods of 12-21 years, females grew more slowly than males in a
      natural population and in two experimental plots where we were able to control
      for genotype, age, habitat, and reproductive history. Simultaneous measurements
      of 10 matched pairs of sibling trees of the opposite sex but same age
      demonstrated that the photosynthetic capacities of females were 13% lower than
      those of males. Among females, photosynthetic capacity was negatively correlated
      with fruit production during the most recent reproductive season but not with
      lifetime fruit production. Sexual size dimorphism in adult O. tenera trees
      appears to be a nonadaptive consequence of trading off recent reproduction
      against maintenance of the photosynthetic apparatus, with long-term negative
      effects on growth.

PMID- 15148384
TI  - Genetic deletion of ghrelin does not decrease food intake but influences
      metabolic fuel preference.
AB  - Ghrelin is a recently identified growth hormone (GH) secretogogue whose
      administration not only induces GH release but also stimulates food intake,
      increases adiposity, and reduces fat utilization in mice. The effect on food
      intake appears to be independent of GH release and instead due to direct
      activation of orexigenic neurons in the arcuate nucleus of the hypothalamus. The
      effects of ghrelin administration on food intake have led to the suggestion that
      inhibitors of endogenous ghrelin could be useful in curbing appetite and
      combating obesity. To further study the role of endogenous ghrelin in appetite
      and body weight regulation, we generated ghrelin-deficient (ghrl(-/-)) mice, in
      which the ghrelin gene was precisely replaced with a lacZ reporter gene. ghrl(-/
      ) mice were viable and exhibited normal growth rates as well as normal
      spontaneous food intake patterns, normal basal levels of hypothalamic orexigenic
      and anorexigenic neuropeptides, and no impairment of reflexive hyperphagia after
      fasting. These results indicate that endogenous ghrelin is not an essential
      regulator of food intake and has, at most, a redundant role in the regulation of
      appetite. However, analyses of ghrl(-/-) mice demonstrate that endogenous ghrelin
      plays a prominent role in determining the type of metabolic substrate (i.e., fat
      vs. carbohydrate) that is used for maintenance of energy balance, particularly
      under conditions of high fat intake.

PMID- 15148386
TI  - Biography of David O. Siegmund.

PMID- 15148385
TI  - Molecular changes in neurons in multiple sclerosis: altered axonal expression of
      Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger.
AB  - Although voltage-gated sodium channels are known to be deployed along
      experimentally demyelinated axons, the molecular identities of the sodium
      channels expressed along axons in human demyelinating diseases such as multiple
      sclerosis (MS) have not been determined. Here we demonstrate changes in the
      expression of sodium channels in demyelinated axons in MS, with Nav1.6 confined
      to nodes of Ranvier in controls but with diffuse distribution of Nav1.2 and
      Nav1.6 along extensive regions of demyelinated axons within acute MS plaques.
      Using triple-labeled fluorescent immunocytochemistry, we also show that Nav1.6,
      which is known to produce a persistent sodium current, and the Na+/Ca2+
      exchanger, which can be driven by persistent sodium current to import damaging
      levels of calcium into axons, are colocalized with beta-amyloid precursor
      protein, a marker of axonal injury, in acute MS lesions. Our results demonstrate
      the molecular identities of the sodium channels expressed along demyelinated and
      degenerating axons in MS and suggest that coexpression of Nav1.6 and Na+/Ca2+
      exchanger is associated with axonal degeneration in MS.

PMID- 15148387
TI  - Reversal of cystic fibrosis phenotype in a cultured Delta508 cystic fibrosis
      transmembrane conductance regulator cell line by oligonucleotide insertion.
AB  - Cystic fibrosis (CF) is a lethal genetic disorder that is due to mutations in the
      gene encoding the cAMP-activated anion CF transmembrane conductance regulator
      (CFTR) channel. A three-nucleotide base deletion (TTT), encoding phenylalanine in
      position 508 of the translatable CFTR sequence (accompanied by a C to T
      replacement immediately 5' to the deletion), accounts for approximately 75% of
      cases of the disease. In the present study, an oligonucleotide complex (CF4-CF6,
      2'-0-methyl RNA-unmodified RNA oligonucleotide duplex, respectively) was used to
      restore CFTR function by insertion of missing bases in Delta508 CFTR mRNA from a
      cultured (Delta508) cell line. cAMP-activated whole-cell currents and Cl-
      transport were detected in CF4-CF6-treated, but not control Delta508, cells by
      patch-clamp and 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescence (SPQ)
      quenching analyses, respectively. Further, the nucleotide addition in the deleted
      region of Delta508 CFTR was determined after amplification by RT-PCR. Insertion
      of UGU and replacement of U by C immediately 5' to the deletion site in Delta508
      mRNA appear to have taken place, with phenotypic but not genotypic reversion in
      tissue culture of treated cells. The mechanism of insertion of nucleotides has
      yet to be determined.

PMID- 15148388
TI  - Camalexin is synthesized from indole-3-acetaldoxime, a key branching point
      between primary and secondary metabolism in Arabidopsis.
AB  - Characteristic for cruciferous plants is their production of N- and S-containing
      indole phytoalexins with disease resistance and cancer-preventive properties,
      previously proposed to be synthesized from indole independently of tryptophan. We
      show that camalexin, the indole phytoalexin of Arabidopsis thaliana, is
      synthesized from tryptophan via indole-3-acetaldoxime (IAOx) in a reaction
      catalyzed by CYP79B2 and CYP79B3. Cyp79B2/cyp79B3 double knockout mutant is
      devoid of camalexin, as it is also devoid of indole glucosinolates [Zhao, Y.,
      Hull, A. K., Gupta, N. R., Goss, K. A., Alonso, J., Ecker, J. R., Normanly, J.,
      Chory, J. & Celenza, J. L. (2002) Genes Dev. 16, 3100-3112], and isotope-labeled
      IAOx is incorporated into camalexin. These results demonstrate that only CYP79B2
      and CYP79B3 contribute significantly to the IAOx pool from which camalexin and
      indole glucosinolates are synthesized. Furthermore, production of camalexin in
      the sur1 mutant devoid of glucosinolates excludes the possibility that camalexin
      is derived from indole glucosinolates. CYP79B2 plays an important role in
      camalexin biosynthesis in that the transcript level of CYP79B2, but not CYP79B3,
      is increased upon induction of camalexin by silver nitrate as evidenced by
      microarray analysis and promoter-beta-glucuronidase data. The structural
      similarity between cruciferous indole phytoalexins suggests that these compounds
      are biogenetically related and synthesized from tryptophan via IAOx by CYP79B
      homologues. The data show that IAOx is a key branching point between several
      secondary metabolic pathways as well as primary metabolism, where IAOx has been
      shown to play a critical role in IAA homeostasis.

PMID- 15148389
TI  - phyllopod is a target gene of proneural proteins in Drosophila external sensory
      organ development.
AB  - Proneural basic helix-loop-helix (bHLH) proteins initiate neurogenesis in both
      vertebrates and invertebrates. The Drosophila Achaete (Ac) and Scute (Sc)
      proteins are among the first identified members of the large bHLH proneural
      protein family. phyllopod (phyl), encoding an ubiquitin ligase adaptor, is
      required for ac- and sc-dependent external sensory (ES) organ development.
      Expression of phyl is directly activated by Ac and Sc. Forced expression of phyl
      rescues ES organ formation in ac and sc double mutants. phyl and senseless,
      encoding a Zn-finger transcriptional factor, depend on each other in ES organ
      development. Our results provide the first example that bHLH proneural proteins
      promote neurogenesis through regulation of protein degradation.

PMID- 15148391
TI  - Resonant optical rectification in bacteriorhodopsin.
AB  - The relative role of retinal isomerization and microscopic polarization in the
      phototransduction process of bacteriorhodopsin is still an open question. It is
      known that both processes occur on an ultrafast time scale. The retinal trans-
      >cis photoisomerization takes place on the time scale of a few hundred
      femtoseconds. On the other hand, it has been proposed that the primary light
      induced event is a sudden polarization of the retinal environment, although there
      is no direct experimental evidence for femtosecond charge displacements, because
      photovoltaic techniques cannot be used to detect charge movements faster than
      picoseconds. Making use of the known high second-order susceptibility chi(2) of
      retinal in proteins, we have used a nonlinear technique, interferometric
      detection of coherent infrared emission, to study macroscopically oriented
      bacteriorhodopsin-containing purple membranes. We report and characterize
      impulsive macroscopic polarization of these films by optical rectification of an
      11-fs visible light pulse in resonance with the optical transition. This finding
      provides direct evidence for charge separation as a precursor event for
      subsequent functional processes. A simple two-level model incorporating the
      resonant second-order optical properties of retinal, which are known to be a
      requirement for functioning of bacteriorhodopsin, is used to describe the
      observations. In addition to the electronic response, long-lived infrared
      emission at specific frequencies was observed, reflecting charge movements
      associated with vibrational motions. The simultaneous and phase-sensitive
      observation of both the electronic and vibrational signals opens the way to study
      the transduction of the initial polarization into structural dynamics.

PMID- 15148390
TI  - Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells
      against apoptosis via antiapoptotic Bcl-2 proteins.
AB  - The neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEA
      sulfate (DHEAS), and allopregnanolone (Allo), produced by the CNS and the
      adrenals, appear to exert a protective effect in hippocampal and cortical neuron
      ischemia- and excitotoxicity-induced injury. We hypothesized that they may also
      play a protective role on the adrenal medulla, an important part of the
      sympathetic nervous system, and the tissue adjacent to their primary site of
      production. DHEA, DHEAS, and Allo protected rat chromaffin cells and the rat
      pheochromocytoma PC12 cell line, an established model for the study of
      adrenomedullary cell apoptosis and survival, against serum deprivation-induced
      apoptosis. Their effects were time- and dose-dependent, with EC50 1.8, 1.1, and
      1.5 nM, respectively. The antiapoptotic effect of DHEA DHEAS and Allo was
      compared to that of a long list of structurally related compounds and was found
      to be structure-specific, confined mainly to conformation 3beta-OH-Delta5 for
      androstenes and 3alpha-OH for pregnanes. Indeed, 3-keto, Delta4, or C7
      hydroxylated androstenes and 3beta pregnanes were ineffective. The prosurvival
      effect of DHEA(S) and Allo was N-methyl-D-aspartate-, GABAA-, sigma1-, or
      estrogen receptor-independent. It involved the antiapoptotic Bcl-2 proteins,
      their role being sine qua non for their action because Bcl-2 antisense
      oligonucleotides reversed their effects. Finally, DHEA(S) and Allo activated cAMP
      response element-binding protein and NF-kappaB, upstream effectors of
      antiapoptotic Bcl-2 protein expression. They also activated the antiapoptotic
      kinase PKCalpha/beta, a posttranslational activator of Bcl-2 protein. Our
      findings suggest that decline of DHEA(S) and Allo during aging or stress may
      leave the adrenal medulla unprotected against proapoptotic challenges.

PMID- 15148392
TI  - Involvement of Per-Arnt-Sim (PAS) kinase in the stimulation of preproinsulin and
      pancreatic duodenum homeobox 1 gene expression by glucose.
AB  - Per-Arnt-Sim (PAS) domain-containing kinases are common in prokaryotes, but a
      mammalian counterpart has only recently been described. Although the PAS domain
      of the mammalian PAS kinase (PASK) is closely related to the bacterial oxygen
      sensor FixL, it is unclear whether PASK activity is changed in mammalian cells in
      response to nutrients and might therefore contribute to signal transduction by
      these or other stimuli. Here, we show that elevated glucose concentrations
      rapidly increase PASK activity in pancreatic islet beta cells, an event followed
      by the accumulation of both PASK mRNA and protein. Demonstrating a physiological
      role for PASK activation, comicroinjection into clonal beta cells of cDNA
      encoding wild-type PASK, or PASK protein itself, mimics the induction of
      preproinsulin promoter activity by high glucose concentrations. Conversely, anti
      PASK antibodies block promoter activation by the sugar, and the silencing of PASK
      expression by RNA interference suppresses the up-regulation by glucose of
      preproinsulin and pancreatic duodenum homeobox 1 gene expression, without
      affecting glucose-induced changes in the levels of mRNAs encoding glucokinase or
      uncoupling protein 2. We conclude that PASK is an important metabolic sensor in
      nutrient-sensitive mammalian cells and plays an unexpected role in the regulation
      of key genes involved in maintaining the differentiated phenotype of pancreatic
      beta cells.

PMID- 15148393
TI  - Cti1/C1D interacts with condensin SMC hinge and supports the DNA repair function
      of condensin.
AB  - Condensin is a conserved five-subunit complex containing two SMC (structural
      maintenance of chromosomes) and three non-SMC subunits and plays a major role in
      mitotic chromosome condensation. Condensin also acts in interphase and is
      required for DNA repair and replication checkpoint control. We attempted to study
      the function of the condensin in greater detail by means of the isolation of
      interacting proteins with the two-hybrid system. Using the hinge domain of
      Cut3/SMC4 as bait, we found one Cut three-interacting (Cti) 14-kDa nuclear
      protein, Cti1. GST pull-down assay and immunoprecipitation supported physical
      interaction between Cti1 and condensin. Cti1 is similar to human C1D, which
      associates tightly with genomic DNA and functions to activate DNA protein kinase.
      SpC1D is essential for viability. The null mutant could germinate but arrest
      after replication, indicating that it is required for interphase growth.
      Importantly, an elevated dosage of spC1D suppressed the temperature, UV
      irradiation, and hydroxyurea sensitivity of the mutant of Cnd2, a non-SMC subunit
      of condensin. Upon exposure to hydroxyurea, spC1D accumulated on the nuclear
      chromatin, and the fraction of spC1D that was chromatin-bound increased. Cti1 is
      the first example of the protein that interacts with the hinge domain of SMC.
      Cti1 may have a supporting role for the DNA repair function of condensin.

PMID- 15148394
TI  - Membrane growth can generate a transmembrane pH gradient in fatty acid vesicles.
AB  - Electrochemical proton gradients are the basis of energy transduction in modern
      cells, and may have played important roles in even the earliest cell-like
      structures. We have investigated the conditions under which pH gradients are
      maintained across the membranes of fatty acid vesicles, a model of early cell
      membranes. We show that pH gradients across such membranes decay rapidly in the
      presence of alkali-metal cations, but can be maintained in the absence of
      permeable cations. Under such conditions, when fatty acid vesicles grow through
      the incorporation of additional fatty acid, a transmembrane pH gradient is
      spontaneously generated. The formation of this pH gradient captures some of the
      energy released during membrane growth, but also opposes and limits further
      membrane area increase. The coupling of membrane growth to energy storage could
      have provided a growth advantage to early cells, once the membrane composition
      had evolved to allow the maintenance of stable pH gradients.

PMID- 15148395
TI  - The twilight of Heliozoa and rise of Rhizaria, an emerging supergroup of amoeboid
      eukaryotes.
AB  - Recent molecular phylogenetic studies revealed the extraordinary diversity of
      single-celled eukaryotes. However, the proper assessment of this diversity and
      accurate reconstruction of the eukaryote phylogeny are still impeded by the lack
      of molecular data for some major groups of easily identifiable and cultivable
      protists. Among them, amoeboid eukaryotes have been notably absent from molecular
      phylogenies, despite their diversity, complexity, and abundance. To partly fill
      this phylogenetic gap, we present here combined small-subunit ribosomal RNA and
      actin sequence data for the three main groups of "Heliozoa" (Actinophryida,
      Centrohelida, and Desmothoracida), the heliozoan-like Sticholonche, and the
      radiolarian group Polycystinea. Phylogenetic analyses of our sequences
      demonstrate the polyphyly of heliozoans, which branch either as an independent
      eukaryotic lineage (Centrohelida), within stramenopiles (Actinophryida), or among
      cercozoans (Desmothoracida), in broad agreement with previous ultrastructure
      based studies. Our data also provide solid evidence for the existence of the
      Rhizaria, an emerging supergroup of mainly amoeboid eukaryotes that includes
      desmothoracid heliozoans, all radiolarians, Sticholonche, and foraminiferans, as
      well as various filose and reticulose amoebae and some flagellates.

PMID- 15148396
TI  - XLalphas, the extra-long form of the alpha-subunit of the Gs G protein, is
      significantly longer than suspected, and so is its companion Alex.
AB  - Because of the use of alternate exons 1, mammals express two distinct forms of
      Gsalpha-subunits: the canonical 394-aa Gsalpha present in all tissues and a 700+
      aa extra-long alphas (XLalphas) expressed in a more restricted manner. Both
      subunits transduce receptor signals into stimulation of adenylyl cyclase. The XL
      exon encodes the XL domain of XLalphas and, in a parallel ORF, a protein called
      Alex. Alex interacts with the XL domain of XLalphas and inhibits its adenylyl
      cyclase-stimulating function. In mice, rats, and humans, the XL exon is thought
      to contribute 422.3, 367.3, and 551.3 codons and to encode Alex proteins of 390,
      357, and 561 aa, respectively. We report here that the XL exon is longer than
      presumed and contributes in mice, rats, and humans, respectively, an additional
      364, 430, and 139 codons to XLalphas. We called the N-terminally extended
      XLalphas extra-extra-long Gsalpha, or XXLalphas. Alex is likewise longer. Its ORF
      also remains open in the 5' direction for approximately 2,000 nt, giving rise to
      Alex-extended, or AlexX. RT-PCR of murine total brain RNA shows that the entire
      XXL domain is encoded in a single exon. Furthermore, we discovered two truncated
      forms of XXLalphas, XXLb1 and XXLb2, in which, because of alternative splicing,
      the Gsalpha domain is replaced by different sequences. XXLb proteins are likely
      to be found as stable dimers with AlexX. The N-terminally longer proteins may
      play regulatory roles.

PMID- 15148397
TI  - The structure of a yeast RNA-editing deaminase provides insight into the fold and
      function of activation-induced deaminase and APOBEC-1.
AB  - Activation-induced deaminase (AID) uses base deamination for class-switch
      recombination and somatic hypermutation and is related to the mammalian RNA
      editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 is a
      yeast ortholog of APOBEC-1 that exhibits cytidine deaminase and RNA-editing
      activity. Here, we present the crystal structure of CDD1 at 2.0-A resolution and
      its use in comparative modeling of APOBEC-1 and AID. The models explain
      dimerization and the need for trans-acting loops that contribute to active site
      formation. Substrate selectivity appears to be regulated by a central active site
      "flap" whose size and flexibility accommodate large substrates in contrast to
      deaminases of pyrimidine metabolism that bind only small nucleosides or free
      bases. Most importantly, the results suggested both AID and APOBEC-1 are equally
      likely to bind single-stranded DNA or RNA, which has implications for the
      identification of natural AID targets.

PMID- 15148398
TI  - Dramatic acceleration of protein folding by stabilization of a nonnative backbone
      conformation.
AB  - Through a mutagenic investigation of Gly-48, a highly conserved position in the
      Src homology 3 domain, we have discovered a series of amino acid substitutions
      that are highly destabilizing, yet dramatically accelerate protein folding, some
      up to 10-fold compared with the wild-type rate. The unique folding properties of
      these mutants allowed for accurate measurement of their folding and unfolding
      rates in water with no denaturant by using an NMR spin relaxation dispersion
      technique. A strong correlation was found between beta-sheet propensity and the
      folding rates of the Gly-48 mutants, even though Gly-48 lies in an unusual non
      beta-strand backbone conformation in the native state. This finding indicates
      that the accelerated folding rates of the Gly-48 mutants are the result of
      stabilization of a nonnative beta-strand conformation in the transition-state
      structure at this position, thus providing the first, to our knowledge,
      experimentally elucidated example of a mechanism by which folding can occur
      fastest through a nonnative conformation. We also demonstrate that residues that
      are most stabilizing in the transition-state structure are most destabilizing in
      the native state, and also cause the greatest reductions in in vitro functional
      activity. These data indicate that the unusual native conformation of the Gly-48
      position is important for function, and that evolutionary selection for function
      can result in a domain that folds at a rate far below the maximum possible.

PMID- 15148399
TI  - A new activity for an old enzyme: Escherichia coli bacterial alkaline phosphatase
      is a phosphite-dependent hydrogenase.
AB  - Genetic analysis indicates that Escherichia coli possesses two independent
      pathways for oxidation of phosphite (Pt) to phosphate. One pathway depends on the
      14-gene phn operon, which encodes the enzyme C-P lyase. The other pathway depends
      on the phoA locus, which encodes bacterial alkaline phosphatase (BAP). Transposon
      mutagenesis studies strongly suggest that BAP is the only enzyme involved in the
      phoA-dependent pathway. This conclusion is supported by purification and
      biochemical characterization of the Pt-oxidizing enzyme, which was proven to be
      BAP by N terminus protein sequencing. Highly purified BAP catalyzed Pt oxidation
      with specific activities of 62-242 milliunits/mg and phosphate ester hydrolysis
      with specific activities of 41-61 units/mg. Surprisingly, BAP catalyzes the
      oxidation of Pt to phosphate and molecular H2. Thus, BAP is a unique Pt
      dependent, H2-evolving hydrogenase. This reaction is unprecedented in both P and
      H biochemistry, and it is likely to involve direct transfer of hydride from the
      substrate to water-derived protons.

PMID- 15148400
TI  - Shape insensitive optimal adhesion of nanoscale fibrillar structures.
AB  - Gecko and many insects have adopted nanoscale fibrillar structures on their feet
      as adhesion devices. Here, we consider adhesion between a single fiber and a
      substrate by van der Waals or electrostatic interactions. For a given contact
      area A, the theoretical pull-off force of the fiber is sigma(th)A where sigma(th)
      is the theoretical strength of adhesion. We show that it is possible to design an
      optimal shape of the tip of the fiber to achieve the theoretical pull-off force.
      However, such design tends to be unreliable at the macroscopic scale because the
      pull-off force is sensitive to small variations in the tip shape. We find that a
      robust design of shape-insensitive optimal adhesion becomes possible only when
      the diameter of the fiber is reduced to length scales on the order of 100 nm. In
      general, optimal adhesion could be achieved by a combination of size reduction
      and shape optimization. The smaller the size, the less important the shape. At
      large contact sizes, optimal adhesion could still be achieved if the shape can be
      manufactured to a sufficiently high precision. The robust design of optimal
      adhesion at nanoscale provides a plausible explanation for the convergent
      evolution of hairy attachment systems in biology.

PMID- 15148401
TI  - The crystal structure of xanthine oxidoreductase during catalysis: implications
      for reaction mechanism and enzyme inhibition.
AB  - Molybdenum is widely distributed in biology and is usually found as a mononuclear
      metal center in the active sites of many enzymes catalyzing oxygen atom transfer.
      The molybdenum hydroxylases are distinct from other biological systems catalyzing
      hydroxylation reactions in that the oxygen atom incorporated into the product is
      derived from water rather than molecular oxygen. Here, we present the crystal
      structure of the key intermediate in the hydroxylation reaction of xanthine
      oxidoreductase with a slow substrate, in which the carbon-oxygen bond of the
      product is formed, yet the product remains complexed to the molybdenum. This
      intermediate displays a stable broad charge-transfer band at approximately 640
      nm. The crystal structure of the complex indicates that the catalytically labile
      Mo-OH oxygen has formed a bond with a carbon atom of the substrate. In addition,
      the MoS group of the oxidized enzyme has become protonated to afford Mo-SH on
      reduction of the molybdenum center. In contrast to previous assignments, we find
      this last ligand at an equatorial position in the square-pyramidal metal
      coordination sphere, not the apical position. A water molecule usually seen in
      the active site of the enzyme is absent in the present structure, which probably
      accounts for the stability of this intermediate toward ligand displacement by
      hydroxide.

PMID- 15148402
TI  - Norepinephrine-deficient mice lack responses to antidepressant drugs, including
      selective serotonin reuptake inhibitors.
AB  - Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted
      disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically
      test roles for NE in mediating acute behavioral changes elicited by different
      classes of antidepressants. To this end, we used the tail suspension test, one of
      the most widely used paradigms for assessing antidepressant activity and
      depression-related behaviors in normal and genetically modified mice. Dbh(-/-)
      mice failed to respond to the behavioral effects of various antidepressants,
      including the NE reuptake inhibitors desipramine and reboxetine, the monoamine
      oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even
      though they did not differ in baseline immobility from Dbh(+/-) mice, which have
      normal levels of NE. Surprisingly, the effects of the selective serotonin
      reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also
      absent or severely attenuated in the Dbh(-/-) mice. In contrast, citalopram (the
      most selective SSRI) was equally effective at reducing immobility in mice with
      and without NE. Restoration of NE by using L-threo-3,4-dihydroxyphenylserine
      reinstated the behavioral effects of both desipramine and paroxetine in Dbh(-/-)
      mice, thus demonstrating that the reduced sensitivity to antidepressants is
      related to NE function, as opposed to developmental abnormalities resulting from
      chronic NE deficiency. Microdialysis studies demonstrated that the ability of
      fluoxetine to increase hippocampal serotonin was blocked in Dbh(-/-) mice,
      whereas citalopram's effect was only partially attenuated. These data show that
      NE plays an important role in mediating acute behavioral and neurochemical
      actions of many antidepressants, including most SSRIs.

PMID- 15148403
TI  - The mechanism of transmembrane S-nitrosothiol transport.
AB  - S-nitrosothiols have been suggested to play an important role in nitric oxide
      (NO)-mediated biological events. However, the mechanisms by which an S
      nitrosothiol (or the S-nitroso functional group) is transferred across cell
      membrane are still poorly understood. We have demonstrated previously that the
      degradation of S-nitrosoglutathione (GSNO) by cells absolutely required the
      presence of cystine in the extracellular medium and proposed a mechanism that
      involved the reduction of cystine to cysteine, followed by the reaction of
      cysteine with GSNO to form S-nitrosocysteine (CysNO), mixed disulfides, and
      nitrosyl anion. In the present study we have assessed the effect of cystine on
      the transfer of the S-nitroso functional group from the extracellular to the
      intracellular space. Using RAW 264.7 cells, we found that the presence of L
      cystine enhanced GSNO-dependent S-nitrosothiol uptake, increasing the
      intracellular S-nitrosothiol level from approximately 60 pmol/mg of protein to
      approximately 3 nmol/mg of protein. The uptake seems to depend on the reduction
      of L-cystine to L-cysteine, which involves the xc- amino acid transport system,
      the transnitrosation between GSNO and L-cysteine to form L-CysNO, and uptake of L
      CysNO via amino acid transport system L. Compared with GSNO, (Z)-1-[N-(3
      ammoniopropyl)-N-[4-(3-aminopropylammonio)butyl]-amino]diazen-1-ium-1,2-diolate,
      an NO donor, is much less effective at intracellular S-nitrosothiol formation in
      the presence of L-cystine or L-cysteine, suggesting that the biochemical changes
      that occur after exposure of cells to S-nitrosothiol, with respect to thiol
      chemistry, are distinctly different from those observed with NO.

PMID- 15148404
TI  - A gene cluster for secondary metabolism in oat: implications for the evolution of
      metabolic diversity in plants.
AB  - The evolution of the ability to synthesize specialized metabolites is likely to
      have been key for survival and diversification of different plant species. Oats
      (Avena spp.) produce antimicrobial triterpenoids (avenacins) that protect against
      disease. The oat beta-amyrin synthase gene AsbAS1, which encodes the first
      committed enzyme in the avenacin biosynthetic pathway, is clearly distinct from
      other plant beta-amyrin synthases. Here we show that AsbAS1 has arisen by
      duplication and divergence of a cycloartenol synthase-like gene, and that its
      properties have been refined since the divergence of oats and wheat. Strikingly,
      we have also found that AsbAS1 is clustered with other genes required for
      distinct steps in avenacin biosynthesis in a region of the genome that is not
      conserved in other cereals. Because the components of this gene cluster are
      required for at least four clearly distinct enzymatic processes (2,3
      oxidosqualene cyclization, beta-amyrin oxidation, glycosylation, and acylation),
      it is unlikely that the cluster has arisen as a consequence of duplication of a
      common ancestor. Although clusters of paralogous genes are common in plants
      (e.g., gene clusters for rRNA and specific disease resistance), reports of
      clusters of genes that do not share sequence relatedness and whose products
      contribute to a single selectable function are rare [Gierl, A. & Frey, M. (2001)
      Planta 213, 493-498]. Taken together, our evidence has important implications for
      the generation of metabolic diversity in plants.

PMID- 15148405
TI  - Computational design of receptors for an organophosphate surrogate of the nerve
      agent soman.
AB  - We report the computational design of soluble protein receptors for pinacolyl
      methyl phosphonic acid (PMPA), the predominant hydrolytic product of the nerve
      agent soman. Using recently developed computational protein design techniques,
      the ligand-binding pockets of two periplasmic binding proteins, glucose-binding
      protein and ribose-binding protein, were converted to bind PMPA instead of their
      cognate sugars. The designs introduce 9-12 mutations in the parent proteins.
      Twelve of 20 designs tested exhibited PMPA-dependent changes in emission
      intensity of a fluorescent reporter with affinities between 45 nM and 10 microM.
      The contributions to ligand binding by individual residues were determined in two
      designs by alanine-scanning mutagenesis, and are consistent with the molecular
      models. These results demonstrate that designed receptors with radically altered
      binding specificities and affinities that rival or exceed those of the parent
      proteins can be successfully predicted. The designs vary in parent scaffold,
      sequence diversity, and orientation of docked ligand, suggesting that the number
      of possible solutions to the design problem is large and degenerate. This
      observation has implications for the genesis of biological function by random
      processes. The designed receptors reported here may have utility in the
      development of fluorescent biosensors for monitoring nerve agents.

PMID- 15148406
TI  - Functional photoreceptor loss revealed with adaptive optics: an alternate cause
      of color blindness.
AB  - There is enormous variation in the X-linked L/M (long/middle wavelength
      sensitive) gene array underlying "normal" color vision in humans. This
      variability has been shown to underlie individual variation in color matching
      behavior. Recently, red-green color blindness has also been shown to be
      associated with distinctly different genotypes. This has opened the possibility
      that there may be important phenotypic differences within classically defined
      groups of color blind individuals. Here, adaptive optics retinal imaging has
      revealed a mechanism for producing dichromatic color vision in which the
      expression of a mutant cone photopigment gene leads to the loss of the entire
      corresponding class of cone photoreceptor cells. Previously, the theory that
      common forms of inherited color blindness could be caused by the loss of
      photoreceptor cells had been discounted. We confirm that remarkably, this loss of
      one-third of the cones does not impair any aspect of vision other than color.

PMID- 15148407
TI  - Inhibition of acute graft-versus-host disease with retention of graft-versus
      tumor effects by the proteasome inhibitor bortezomib.
AB  - Graft-versus-host disease (GVHD) represents a major hurdle impeding the efficacy
      of allogeneic bone marrow transplantation (BMT). Bortezomib is a proteasome
      inhibitor that was recently approved for treatment of myeloma. We found that
      bortezomib potently inhibited in vitro mixed lymphocyte responses and promoted
      the apoptosis of alloreactive T cells. Bortezomib given at the time of allogeneic
      BMT in mice resulted in significant protection from acute GVHD. Reductions in
      GVHD-associated parameters and biological evidence of proteasome inhibition were
      observed with this regimen but with no adverse effects on long-term donor
      reconstitution. Assessment of graft-versus-tumor responses in advanced leukemia
      bearing mice demonstrated that only the combination of allogeneic BMT and T cells
      with bortezomib promoted significant increases in survival. Increased cytotoxic T
      cell killing of the tumor was also observed. Thus, the combination of proteasome
      inhibition with selective immune attack can markedly increase the efficacy of BMT
      in cancer.

PMID- 15148408
TI  - Inhibitor of kappaB kinase is required to activate a subset of interferon gamma
      stimulated genes.
AB  - IkappaB kinase (IKK), discovered as the major activator of NF-kappaB, plays
      additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking
      both the alpha and beta subunits of IKK, we find that these proteins are required
      for induction of a major subset of IFNgamma-stimulated genes and that this
      requirement is independent of NF-kappaB activation. Furthermore, there is no
      defect in IFNgamma-stimulated signal transducer and activator of transcription 1
      (Stat1) activation or function in the IKKalpha/beta-null MEFs. Therefore,
      although activated Stat1 dimers are necessary for the activation of these genes
      in response to IFNgamma, they are not sufficient. These results reveal an
      important additional pathway for IFNgamma-stimulated gene expression in which an
      NF-kappaB-independent function of IKK is required.

PMID- 15148409
TI  - Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor
      (ICAT), a negative regulator of Wnt signaling.
AB  - Inhibitor of beta-catenin and T cell factor (ICAT) inhibits Wnt signaling by
      interfering with the interaction between beta-catenin and T cell factor. Here we
      show that ICAT(-/-) embryos exhibit malformation of the forebrain and
      craniofacial bones and lack the kidney. Analysis of the neuronal differentiation
      of embryonic stem cells revealed that Wnt3a redirects the fate of neural
      progenitors to a posterior character, whereas ICAT induces forebrain cells by
      inhibiting Wnt signaling. Furthermore, ICAT(-/-) embryonic stem cells were found
      to differentiate into neuronal cells possessing a posterior character. These
      results suggest that ICAT plays an important role in the anteriorization of
      neural cells by inhibiting the posteriorizing activity of Wnt signaling.

PMID- 15148410
TI  - Deletion of the Parkin coregulated gene causes male sterility in the
      quaking(viable) mouse mutant.
AB  - Quaking(viable) (qk(v)) is a recessive neurological mouse mutation with severe
      dysmyelination of the CNS and spermiogenesis failure. The molecular lesion in the
      qk(v) mutant is a deletion of approximately 1 Mb on mouse chromosome 17 that
      alters the expression of the qk gene in oligodendrocytes. Complementation
      analysis between the qk(v) mutation and qk mutant alleles generated through
      chemical mutagenesis showed that the male sterility is a distinctive feature of
      the qk(v) allele. This observation suggested that the sperm differentiation
      defect in qk(v) is due to the deletion of a gene(s) distinct from qk. Here, we
      demonstrate that the deletion of Pacrg is the cause of male sterility in the
      qk(v) mutant. Pacrg is the mouse homologue of the human PARKIN-coregulated gene
      (PACRG), which encodes for a protein whose biochemical function remains unclear.
      We show that Pacrg is highly expressed in the testes in both mice and humans. In
      addition, the expression pattern of Pacrg during spermiogenesis suggests that it
      plays a role in sperm differentiation. In support of this hypothesis, we show
      that transgenic expression of Pacrg in testes restores spermiogenesis and
      fertility in qk(v) males. This finding provides the first in vivo evidence, to
      our knowledge, for the function of Pacrg in a model organism. Immunolocalization
      experiments on isolated spermatozoa show that the Pacrg protein is present in
      mature sperm. Remarkably, the mammalian Pacrg protein shares significant sequence
      similarities with gene products from flagellated protozoans, suggesting that
      Pacrg may be necessary for proper flagellar formation in many organisms.

PMID- 15148413
TI  - Public databases: retrieving and manipulating sequences for beginners.
AB  - This chapter outlines the basic requirements for finding and exploring sequences
      of interest in public databases, such as GenBank. As such, it is not aimed at
      experienced sequencers, for whom this will be "second nature," but at the many
      clinical bacteriologists who rarely have need of DNA sequences in their usual
      work, and who would like to develop their interest in what can appear to be a
      daunting area. The topics discussed include finding and retrieving sequences from
      GenBank, identifying homologous sequences using BLAST searches, resources for
      accessing microbial genomes, and the Protein Data Bank. Finally, recommendations
      are made for useful software (freeware) and online sequence manipulation
      resources.

PMID- 15148412
TI  - Bacterial genomes for the masses: relevance to the clinical laboratory.
AB  - Bacterial genome sequencing has revolutionized the research landscape and
      promises to deliver important changes to the clinical microbiology laboratory,
      through the identification of novel diagnostic targets and through the birth of a
      new discipline or "genomic epidemiology." Current progress and future prospects
      for exploitation of genome sequences in clinical bacteriology are reviewed.

PMID- 15148411
TI  - Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated
      apoptosis by binding and sequestering Bax at mitochondria.
AB  - We report that the cytomegalovirus-encoded cell death suppressor vMIA binds Bax
      and prevents Bax-mediated mitochondrial membrane permeabilization by sequestering
      Bax at mitochondria in the form of a vMIA-Bax complex. vMIA mutants with a
      defective mitochondria-targeting domain retain their Bax-binding function but not
      their ability to suppress mitochondrial membrane permeabilization or cell death.
      vMIA does not seem to either specifically associate with Bak or suppress Bak
      mediated mitochondrial membrane permeabilization. Recent evidence suggests that
      the contribution of Bax and Bak in the mitochondrial apoptotic signaling pathway
      depends on the distinct phenotypes of cells, and it appears from our data that
      vMIA is capable of suppressing apoptosis in cells in which this pathway is
      dominated by Bax, but not in cells where Bak also plays a role.

PMID- 15148414
TI  - Genome sequencing and annotation: an overview.
AB  - Many microbial genome sequences have been determined, and more new genome
      projects are ongoing. Shotgun sequencing of randomly cloned short pieces of
      genomic DNA can provide a simple way of determining whole genome sequences. This
      process requires sequencing of many fragments, compilation of the separate
      sequences into one contiguous sequence, and careful editing of the assembled
      sequence. The genes present on the microbial genome are then predicted using
      clues derived from typical gene features, such as codon usage, ribosomal binding
      sequences, and bacterial initiation codons. Function of genes is predicted by
      homology searches performed against either public or well-established protein
      databases. This chapter discusses each of these stages in a genome-sequencing
      project.

PMID- 15148415
TI  - Comparative genomics: digging for data.
AB  - Comparative genomics is a science in its infancy. It has been driven by a huge
      increase in freely available genome-sequence data, and the development of
      computer techniques to allow whole-genome sequence analyses. Other approaches,
      which use hybridization as a method for comparing the gene content of related
      organisms, are rising alongside these more bioinformatic methods. All these
      approaches have been pioneered using bacterial genomes because of their
      simplicity and the large number of complete genome sequences available. The aim
      of bacterial comparative genomics is to determine what genotypic differences are
      important for the expression of particular traits. The benefits of such studies
      will be a deeper understanding of these phenomena; the possibility of exposing
      novel drug targets, including those for antivirulence drugs; and the development
      of molecular techniques that reveal patients who are infected with virulent
      organisms so that health care resources can be allocated appropriately. With more
      and more genome sequences becoming available, the rise of comparative genomics
      continues apace.

PMID- 15148416
TI  - Genome plasticity: insertion sequence elements, transposons and integrons, and
      DNA rearrangement.
AB  - Living organisms are defined by the genes they possess. Control of expression of
      this gene set, both temporally and in response to the environment, determines
      whether an organism can survive changing conditions and can compete for the
      resources it needs to reproduce. Bacteria are no exception; changes to the genome
      will, in general, threaten the ability of the microbe to survive, but acquisition
      of new genes may enhance its chances of survival by allowing growth in a
      previously hostile environment. For example, acquisition of an antibiotic
      resistance gene by a bacterial pathogen can permit it to thrive in the presence
      of an antibiotic that would otherwise kill it; this may compromise clinical
      treatments. Many forces, chemical and genetic, can alter the genetic content of
      DNA by locally changing its nucleotide sequence. Notable for genetic change in
      bacteria are transposable elements and site-specific recombination systems such
      as integrons. Many of the former can mobilize genes from one replicon to another,
      including chromosome-plasmid translocation, thus establishing conditions for
      interspecies gene transfer. Balancing this, transposition activity can result in
      loss or rearrangement of DNA sequences. This chapter discusses bacterial DNA
      transfer systems, transposable elements and integrons, and the contributions each
      makes towards the evolution of bacterial genomes, particularly in relation to
      bacterial pathogenesis. It highlights the variety of phylogenetically distinct
      transposable elements, the variety of transposition mechanisms, and some of the
      implications of rearranging DNA, and addresses the effects of genetic change on
      the fitness of the microbe.

PMID- 15148417
TI  - Exploring and exploiting bacterial proteomes.
AB  - The plethora of data now available from bacterial genome sequencing has opened a
      wealth of new research opportunities. Many of these have been reviewed in
      preceding chapters. Genomics alone, however, cannot capture a biological snapshot
      from an organism at a given point in time. The genome itself is static, and it is
      the changes in expression of genes, leading to the production of functional
      proteins, which allows an organism to survive and adapt to a constantly changing
      environment. Proteomics is the term used to describe the global analysis of
      proteins involved in a particular biological process. Such processes may be
      analyzed via comparative studies that examine bacterial strain differences, both
      phenotypic and genetic, bacteria grown under nutrient limiting conditions, growth
      phase, temperature, or in the presence of chemical compounds, such as
      antibiotics. Proteomics also provides the researcher with a tool to begin
      characterizing the functions of the vast proportion of "hypothetical" or
      "unknown" proteins elucidated from genome sequencing and database comparisons.
      For example, study of protein-protein, protein-ligand, protein-substrate, and
      protein-nucleic acid interactions for a given target protein may all help to
      define the functions of previously unknown proteins. Furthermore, genetic
      manipulation combined with proteomics technologies can provide an understanding
      of how gene expression is regulated. This chapter examines the technologies used
      in proteome analysis and the applications of proteomics to microbiological
      research, with an emphasis on clinically-relevant bacteria.

PMID- 15148418
TI  - Molecular diagnostics: current options.
AB  - Diagnostic medical bacteriology consists of two main components: identification
      and typing. Molecular biology has the potential to revolutionize the way in which
      diagnostic tests are delivered in order to optimize the care of infected
      patients, whether they are in hospital or in the community. Since the discovery
      of the polymerase chain reaction (PCR) in the late 1980s, an enormous amount of
      research has enabled the introduction of molecular tests into several areas of
      routine clinical microbiology. Molecular biology techniques continue to evolve
      rapidly, and many laboratories have been reluctant to introduce these new methods
      due to concerns that the technology would become outdated. In consequence, the
      vast majority of clinical bacteriology laboratories do not currently use any
      molecular diagnostics, although such technology is becoming more widespread in
      specialized regional laboratories, as well as in national reference laboratories.
      Presently, molecular biology offers a wide repertoire of techniques and
      permutations. This chapter is intended to explore the application of these in the
      diagnostic laboratory setting.

PMID- 15148419
TI  - Molecular diagnostics: future probe-based strategies.
AB  - Nucleic acid amplification technologies (NAATs) represent powerful tools in
      clinical microbiology, particularly in areas where traditional culture-based
      methods alone prove insufficient. A notable advantage is in reducing the time
      from taking samples to reporting results. This, and the specificity and
      sensitivity imparted by NAATs, can help to improve patient care. Both thermal and
      isothermal NAATs have been adapted to aid diagnosis in clinical laboratories.
      Current molecular diagnostic assays are generally high-tech, and are expensive to
      buy and perform. Easy-to-use NAATs are beginning to appear, not only facilitating
      acceptable throughput in clinical laboratories, but also allowing tests to move
      out of the laboratory, closer to the point of care. Demand for simpler,
      miniaturized equipment and assays, and the trend toward personalized medicine, is
      leading towards the development of fully integrated automation and home-use kits.
      The integration of diverse disciplines, such as genomics, molecular biology,
      microelectromechanical systems, microfluidics, microfabrication, and organic
      chemistry, is behind the emerging DNA microarray technology. Development of DNA
      microchips allows the simultaneous detection of potentially thousands of target
      sequences, not only favoring high throughput, but also the potential for
      genotyping patient subsets with respect to their response to particular drug
      types (pharmakogenomics). It is envisaged that the future of probe-based
      technologies will see the development of fully integrated assays and devices
      suitable for nonskilled users.

PMID- 15148421
TI  - Microarrays for bacterial typing: realistic hope or holy grail?
AB  - Microbiology has entered the postgenomic era and it is clear that bacterial
      typing should aim to be based on analysis of complete genomes. Although complete
      genome sequencing for epidemiological typing remains unrealistic for the present,
      microarrays that provide information on gene content are now becoming available.
      Microarrays comprised of several thousand probes on glass slides can now be
      manufactured in the laboratory using robotic arrayers. The gene probes are either
      PCR products or synthetic oligonucleotides that can be irreversibly attached to a
      reactive glass surface. The target nucleic acids to be hybridized to the probe
      array are tagged with fluorescent dyes. Relative probe hybridization signals can
      be measured when two or more different preparations are labeled with
      distinguishable fluorophores. Microarrays that include probes for every gene
      within a genome provide excellent comparative data, although a focus on variable
      genes may be more useful for typing purposes. Composite arrays of variable genes
      are under development.

PMID- 15148420
TI  - Real-time PCR.
AB  - The development of instruments that allow real-time monitoring of fluorescence
      within PCR reaction vessels is a significant advance in clinical bacteriology.
      The technology is very flexible, and many alternative instruments and fluorescent
      probe systems are currently available. Real-time PCR assays can be completed very
      rapidly, because no manipulations are required after amplification.
      Identification of amplification products by probe detection in real time is
      highly accurate compared with size analysis on gels. Analysis of the progress of
      the reaction allows accurate quantification of the target sequence over a very
      wide dynamic range, provided suitable standards are available. Finally, probe
      melting analysis can detect sequence variants including single base mutations.

PMID- 15148422
TI  - Genomic approaches to antibacterial discovery.
AB  - This chapter describes two key strategies for the discovery of new antibacterial
      agents and illustrates the critical role played by genomics in each. The first
      approach is genomic target-based screening. Comparative genomics and
      bioinformatics are used to identify novel, selective antibacterial targets of the
      appropriate antibacterial spectrum. Genetic technologies integral for the success
      of this approach, such as essentiality testing, are also described. An
      unprecedented number of novel targets have been discovered via this approach, and
      a plethora of examples are discussed. This section concludes with the case
      history of a target successfully progressed from identification by genomics, to
      high-throughput screening, and onto proof of concept in curing experimental
      infections. The second approach is based on screening for compounds with
      antibacterial activity and then employing a broad variety of newer technologies
      to identify the molecular target of the antibacterial agent. The advantage of
      this approach is that compounds already possess antibacterial activity, which is
      a property often challenging to engineer into molecules obtained from enzyme
      based screening approaches. The recent development of novel biochemical and
      genomic technologies that facilitate identification and characterization of the
      mode of action of these agents has made this approach as attractive as the
      genomic target-based screening strategy.

PMID- 15148424
TI  - Identification of novel pathogenicity genes by PCR signature-tagged mutagenesis
      and related technologies.
AB  - Microbial pathogens possess a repertoire of virulence determinants that make
      unique contributions to bacterial fitness during infection. In this chapter, we
      focus on the recent progress and adaptations of signature-tagged mutagenesis
      (STM) by PCR instead of hybridization. This is a PCR-based STM mutation-based
      screening method using a population of bacterial mutants for the simultaneous
      identification of multiple virulence genes in microbial pathogens by negative
      selection. Modifications of STM developed in our laboratory have been applied to
      Pseudomonas aeruginosa PAO1. Screening of a collection of 6912 STM mutants in the
      rat chronic lung model of infection identified 214 P. aeruginosa STM mutants
      defective in virulence. For further studies, and to illustrate better the
      strategies that need to be utilized, we present detailed analysis of nine
      selected STM mutants. The data obtained indicate that in vivo, defects in
      virulence give a wide variety of phenotypes: defects in known virulence factors
      have been found, thereby validating the method; defects have also been found in
      orthologs with predicted functions, and in some genes whose functions cannot be
      predicted from databases. A general strategy and a simple scenario is discussed
      using the nine STM mutants selected for further characterization. PCR-based STM
      represent a genomics-based method for in vivo high-throughput screening of new
      virulence factors.

PMID- 15148423
TI  - Using the genome to understand pathogenicity.
AB  - Genome sequencing, the determination of the complete complement of DNA in an
      organism, is revolutionizing all aspects of the biological sciences. Genome
      sequences make available for scientific scrutiny the complete genetic capacity of
      an organism. With respect to microbes, this means we now have the unprecedented
      opportunity to investigate the molecular basis of commensal and virulence
      behavior. We now have genome sequences for a wide range of bacterial pathogens
      (obligate, facultative, and opportunistic); this has facilitated the discovery of
      many previously unidentified determinants of pathogenicity and has provided novel
      insights into what creates a pathogen. In-depth analyses of bacterial genomes are
      also providing new perspectives on bacterial physiology, molecular adaptation to
      a preferred niche, and genomic susceptibility to the uptake of foreign DNA, three
      key factors that can play a significant role in determining whether a species, or
      a strain, will have pathogenic potential.

PMID- 15148425
TI  - Discovering new pathogens: culture-resistant bacteria.
AB  - Recent advances in gene-amplification technology and molecular phylogenetics have
      provided the means of detecting and classifying bacteria directly from their
      natural habitats without the need for culture. These techniques have
      revolutionized environmental microbiology, and it is now apparent that the global
      diversity of microorganisms is much greater than previously thought. In the
      context of clinical microbiology, this molecular-based approach has facilitated
      the characterization of culture-resistant bacteria associated with human disease.
      Examples include Helicobacter heilmannii, a cause of gastritis, Tropheryma
      whippeli (the agent of Whipple's disease), and the agents of human ehrlichiosis
      and bacillary angiomatosis. Molecular-based techniques also provide a means of
      investigating complex bacterial flora within the human ecosystem, such as feces
      and dental plaque, without the bias of culture-based isolation. This has given a
      new perspective to the study of polymicrobial infections such as gingivitis, and
      offers the potential for the detection and identification of novel bacterial
      pathogens from among complex and numerous endogenous microbial flora.

PMID- 15148426
TI  - Exploring the concept of clonality in bacteria.
AB  - Isolates of bacterial species that are indistinguishable in genotype are assigned
      as a clone, with the implication that they are descended from the same recent
      ancestor. Clones are difficult to define with precision since bacteria are not
      truly asexual, and recombinational replacements result in diversification of the
      ancestral genotype of a clone, to produce a cluster of increasingly diverse
      genotypes (a clonal complex). The rate at which clonal diversification occurs
      depends on the extent of recombination, which varies among bacteria, so that some
      species have rather stable clones (e.g., Salmonella enterica), whereas in other
      species (e.g., Helicobacter pylori) clones may be so transient that they cannot
      readily be discerned. Clones and clonal complexes need to be assigned by indexing
      genetic variation that is selectively neutral, and currently this is best
      achieved using multilocus sequence typing. Some species of bacterial pathogens
      are very diverse, whereas others are genetically uniform, and some are, in
      essence, a single clone of a mother species that has been raised to species
      status due to the distinctiveness of the disease it causes (e.g., Yersinia
      pestis, Salmonella typhi, or Burkholderia mallei). The population structures of
      bacteria depend on the rate of recombination, and comparative measures of the
      extent of recombination during clonal diversification can be obtained from
      multilocus sequence typing data, as can measures of the longer-term impact of
      recombination. These studies show a wide range of recombination rates among
      bacterial species, and indicate that recombination in many bacteria has been
      sufficiently extensive that a reliable evolutionary history of the species cannot
      be inferred.

PMID- 15148427
TI  - Bacterial taxonomics: finding the wood through the phylogenetic trees.
AB  - Bacterial taxonomy comprises systematics (theory of classification), nomenclature
      (formal process of naming), and identification. There are two basic approaches to
      classification. Similarities may be derived between microorganisms by numerical
      taxonomic methods based on a range of present-day observable characteristics
      (phenetics), drawing in particular on conventional morphological and
      physiological test characters as well as chemotaxonomic markers such as whole
      cell protein profiles, mol% G+C content, and DNA-DNA homologies. By contrast,
      phylogenetics, the process of reconstructing possible evolutionary relationships,
      uses nucleotide sequences from conserved genes that act as molecular
      chronometers. A combination of both phenetics and phylogenetics is referred to as
      polyphasic taxonomy, and is the recommended strategy in description of new
      species and genera. Numerical analysis of small-subunit ribosomal RNA genes
      (rDNA) leading to the construction of branching trees representing the distance
      of divergence from a common ancestor has provided the mainstay of microbial
      phylogenetics. The approach has some limitations, particularly in the
      discrimination of closely related taxa, and there is a growing interest in the
      use of alternative loci as molecular chronometers, such as gyrA and RNAase P
      sequences. Comparison of the degree of congruence between phylogenetic trees
      derived from different genes provides a valuable test of the extent they
      represent gene trees or species trees. Rapid expansion in genome sequences will
      provide a rich source of data for future taxonomic analysis that should take into
      account population structure of taxa and novel methods for analysis of nonclonal
      bacterial populations.

PMID- 15148428
TI  - First bent form for the hydroxo-bridged cis-diammineplatinum(II) dimer
      [Pt(2)(NH(3))(4)(micro-OH)(2)](ClO(4))(2).
AB  - The third crystal structure containing the hydroxo-bridged cis
      diammineplatinum(II) dimer has been determined for a perchlorate salt of the
      complex, [Pt(2)(NH(3))(4)(micro-OH)(2)](ClO(4))(2). However, the dinuclear
      cations in the nitrate and the carbonate salts, [Pt(2)(NH(3))(4)(micro
      OH)(2)](NO(3))(2) [Faggiani, Lippert, Lock & Rosenberg (1977). J. Am. Chem. Soc.
      99, 777-781] and [Pt(2)(NH(3))(4)(micro-OH)(2)](CO(3)).H(2)O [Lippert, Lock,
      Rosenberg & Zvagulis (1978). Inorg. Chem. 17, 2971-2975], were reported to
      possess a nearly planar geometry. The cation in the title perchlorate salt has
      been found to possess an exceptional bent form in which two Pt coordination
      planes within the dimer are tilted at an angle of 151.7 (1) degrees to one
      another. The diplatinum entity has a syn orientation with regard to the
      conformation of two hydroxo bridges, in part due to the one-dimensional hydrogen
      bonding network achieved in the crystal structure. DFT MO investigations have
      also been carried out to reveal that the planar-bent selection could be induced
      by the anti-syn selection at the H(hydroxo) atoms. Comparison has also been made
      between the geometrical features of the three salts from the viewpoint of the
      orientation of H(hydroxo) atoms.

PMID- 15148429
TI  - New view of the high-pressure behaviour of GdFeO(3)-type perovskites.
AB  - Recent determinations of the structures of several GdFeO(3)-type orthorhombic
      perovskites (ABO(3)) show that the octahedra in some become more tilted with
      increasing pressure. In others the octahedra become less tilted and the structure
      evolves towards a higher-symmetry configuration. This variety of behaviour can be
      explained in terms of the relative compressibilities of the octahedral and
      dodecahedral cation sites in the perovskite structure. If the BO(6) octahedra are
      less compressible than the AO(12) sites then the perovskite will become more
      distorted with pressure, but the perovskite will become less distorted if the
      BO(6) site is more compressible than the AO(12) site. In this contribution we use
      the bond-valence concept to develop a model that predicts the relative
      compressibilities of the cation sites in oxide perovskites. We introduce the site
      parameter M(i) defined in terms of the coordination number N(i), average bond
      length at room pressure R(i), and the bond-valence parameters R(0) and B,M(i) =
      ([R(i)N(i)/B)exp](R(0) - R(i))/B].M(i) represents the variation in the bond
      valence sum at the central cation in a polyhedral site because of the change of
      the average bond distance. Experimental data suggest that the pressure-induced
      changes in the bond-valence sums at the two cation sites within any given
      perovskite are equal. With this condition we show that the ratio of cation-site
      compressibilities is given by betaB/beta(A) = M(A)/M(B). This model, based only
      upon room-pressure bond lengths and bond-valence parameters, correctly predicts
      the structural behaviour and some physical properties of the oxide perovskites
      that have been measured at high pressure.

PMID- 15148430
TI  - Mg(1 + x)Ir(1 - x) (x = 0, 0.037 and 0.054), a binary intermetallic compound with
      a new orthorhombic structure type determined from powder and single-crystal X-ray
      diffraction.
AB  - The new binary compound Mg(1 + x)Ir(1 - x) (x = 0-0.054) was prepared by melting
      the elements in the Mg:Ir ratio 2:3 in a sealed tantalum tube under an argon
      atmosphere in an induction furnace (single crystals) or by annealing cold-pressed
      pellets of the starting composition Mg:Ir 1:1 in an autoclave under an argon
      atmosphere (powder sample). The structure was independently solved from high
      resolution synchrotron powder and single-crystal X-ray data: Pearson symbol
      oC304, space group Cmca, lattice parameters from synchrotron powder data a =
      18.46948 (6), b = 16.17450 (5), c = 16.82131 (5) A. Mg(1 + x)Ir(1 - x) is a
      topologically close-packed phase, containing 13 Ir and 12 Mg atoms in the
      asymmetric unit, and has a narrow homogeneity range. Nearly all the atoms have
      Frank-Kasper-related coordination polyhedra, with the exception of two Ir atoms,
      and this compound contains the shortest Ir-Ir distances ever observed. The
      solution of a rather complex crystal structure from powder diffraction, which was
      fully confirmed by the single-crystal method, shows the power of powder
      diffraction in combination with the high-resolution data and the global
      optimization method.

PMID- 15148432
TI  - 30 space-group corrections: two examples of false polymorphism and one of
      incorrect interpretation of the fine details of an IR spectrum.
AB  - Revised structures are reported for 30 crystalline compounds, based on space
      groups of higher symmetry than originally reported. In 18 cases the Laue class is
      revised, in seven cases the center of symmetry is added, in two cases the Laue
      class change is coupled with the addition of the center of symmetry, in two cases
      the addition of the center of symmetry also requires the addition of systematic
      absences and, finally, one case of the addition of systematic absences without
      changing the Laue group is reported. Two examples (CSD refcodes: DAMLIM and
      ABPZCU01) of false polymorphism and one (PAVJUR) of the erroneous interpretation
      of the fine details of IR spectra, owing to incorrect space-group determination,
      have been detected.

PMID- 15148431
TI  - Structural study of Cu(2-x)Se alloys produced by mechanical alloying.
AB  - The crystalline structures of the superionic high-temperature copper selenides
      Cu(2-x)Se (0 < x < 0.25) produced using mechanical alloying were investigated
      using X-ray diffraction (XRD). The measured XRD patterns showed the presence of
      peaks corresponding to the crystalline superionic high-temperature alpha-Cu(2)Se
      phase in the as-milled sample, and its structural data were determined by means
      of a Rietveld refinement procedure. After heat treatment in argon at 473 K for 90
      h, this phase transforms to the superionic high-temperature alpha-Cu(1.8)Se
      phase, whose structural data were also determined by Rietveld refinement. In this
      phase, a very low occupation of the trigonal 32(f) sites ( approximately 3%) by
      Cu ions is found. In order to explain the evolution of the phases in the samples,
      two possible mechanisms are suggested: (i). the high mobility of Cu ions in
      superionic phases and (ii). the important diffusive processes in the interfacial
      component of samples produced by mechanical alloying.

PMID- 15148433
TI  - Non-aromatic endocyclic angle at the ring fusion with the aromatic ring in
      benzocyclopentene and -hexene, revisited.
AB  - X-ray geometries of monocycloalkenobenzenes with a fused-ring size of r = 5, 6
      were obtained by the use of the Cambridge Structural Database. In contrast to
      Allen's study [Acta Cryst. (1981), B37, 900-906], the data were not averaged over
      exact or imposed m(ad) symmetry (m(ad) is the mirror plane going through the
      midpoint of the aromatic ring fusion bond and the aromatic bond parallel to it).
      The distribution of the non-aromatic endocyclic angle epsilon at the ring fusion
      clearly shows two and three, respectively, distinct curves for r = 5 and r = 6.
      The respective ranges are 104.3-112.6 and 104.4-123.2 degrees. If one of the C
      atoms directly attached to the aromatic ring is sp(2) hybridized, the bond length
      e between the aromatic ring and this atom is shortened by some 0.044 (15) and
      0.027 (12) A for r = 5 and r = 6, respectively. However, for r = 5, e is only
      shortened by 0.030 (17) A when both C atoms directly attached to the aromatic
      ring are sp(2) hybridized. For r = 5, the endocyclic angle epsilon is 1.2 (13)
      degrees smaller at the side involving the sp(2) hybridized C atom.

PMID- 15148434
TI  - A new polymorph of ortho-ethoxy-trans-cinnamic acid: single-to-single-crystal
      phase transformation and mechanism.
AB  - The alpha-polymorph of ortho-ethoxy-trans-cinnamic acid (OETCA) undergoes a
      reversible single-crystal-to-single-crystal phase transformation at 333 K. The
      new high-temperature polymorph (alpha'-OETCA) is stable between 333 and 393 K
      with three molecules in the asymmetric unit (Z' = 3), space group P1;. Unlike the
      other polymorphs (and solvate) of OETCA recently reported, two of the molecules
      in alpha'-OETCA deviate significantly from planarity. This conformational change
      results in the corrugated sheet-type structure of alpha'-OETCA. The sheets are
      made up of ribbons, each composed of R(2)(2)(8) hydrogen-bonded pairs (via the 
      COOH groups), which are further connected by CH.O interactions. When exposed to
      UV radiation the alpha'-OETCA polymorph can be stabilized below 333 K with ca 8%
      of the monomer converted into the photodimer. The crystal structures of alpha'
      OETCA are reported at two temperatures above the phase transition point (at 345
      and 375 K) as well as the stabilized forms at 173 and 293 K. A mechanism for the
      phase transition involving a cooperative conformational transformation coupled
      with a shift of layers of OETCA molecules is proposed. The alpha'-OETCA polymorph
      is also an example of a cinnamic acid derivative where two different potentially
      photoreactive environments exist in one crystal in which each unit cell has two
      non-centrosymmetric predimer sites and one centrosymmetric predimer site.

PMID- 15148435
TI  - Photodimerization of the alpha'-polymorph of ortho-ethoxy-trans-cinnamic acid in
      the solid state. I. Monitoring the reaction at 293 K.
AB  - Structural changes that occur during the [2 + 2] photodimerization of the
      metastable alpha'-polymorph of ortho-ethoxy-trans-cinnamic acid at 293 K are
      presented here. Crystals of the alpha'-polymorph were first stabilized by
      exposing the alpha-polymorph to UV light for a short period of time at 343 K. The
      photodimerization reaction was then carried out at 293 K and observed in situ by
      single-crystal X-ray diffraction. The alpha'-polymorph contains three molecules
      in the asymmetric unit, labelled A, B and C, which are arranged to form two
      potential reaction sites. The intermolecular distance between the C=C bonds of
      molecules A and B (making up the AB site) is 3.6 A, and these were observed to
      undergo photodimerization at 293 K. The corresponding distance between
      centrosymmetrically related C=C bonds in the CC site (made up of C molecules) is
      4.6 A, and these remain unreacted even after 60 h irradiation at 293 K. The
      crystal of the final product, which corresponds to a 66.7% conversion (only two
      out of three molecules in the asymmetric unit take part in the photodimerization
      reaction at 293 K), contains an ordered arrangement of the photodimer and
      unreacted monomer. The crystal retains many structural features of the original
      monomer crystal, including carboxylic acid hydrogen bonds and C-H.O interactions.
      Single-crystal X-ray diffraction was used to monitor changes in the unit-cell
      parameters, reacting molecules and molecular conformations as the reaction
      progressed. The conformation of the photodimer obtained from the solid-state
      reaction differs from that of the photodimer obtained by recrystallization from
      solution.

PMID- 15148437
TI  - Structural phase transitions, and Br.N and Br.Br interactions in 1-phenyl-2
      methyl-4-nitro-5-bromoimidazole.
AB  - Crystals of C(10)H(8)N(3)O(2)Br undergo two reversible phase transitions between
      295 and 100 K. The first, of an order-disorder nature, is a second-order
      transition and takes place continuously over a wide temperature range. This
      transition is connected with the doubling of the length of the c axis of the unit
      cell and with the change of the space group from P2(1)/m with Z' = 1/2 (room
      temperature alpha-phase) to P2(1)/c, Z' = 1 (beta-phase, 200-120 K). During this
      transition the molecule loses the C(s) symmetry of the alpha-phase. The second
      transition takes place between 118 and 115 K, and is accompanied by a change of
      the crystal symmetry to the triclinic space group P1; (low-temperature gamma
      phase). This second phase transition is accompanied by the twinning of the
      crystal. Neither the molecular geometry nor the crystal packing shows any
      dramatic changes during these phase transitions. Halogen bonds C-Br.N and
      dihalogen interactions Br.Br play a crucial role in determining the crystal
      packing and compete successfully with other kinds of weak intermolecular
      interactions.

PMID- 15148436
TI  - Packing conflicts in the Z' = 5 structure of CF(3)(CF(2))(3)(CH(2))(10)COOH.
AB  - Dimers of the partially fluorinated amphiphile 1-(perfluorobutyl)undecanoic acid,
      CF(3)(CF(2))(3)(CH(2))(10)COOH, crystallize in the same basic packing arrangement
      found for many n-alkyl carboxylic acids. The unit cell of the fluorinated
      compound, however, contains five independent molecules rather than the one found
      for most n-alkyl carboxylic acids including CH(3)(CH(2))(13)COOH. The structures
      of the two C(15) acids are compared. The structural modulations that lead to the
      large value of Z' can be understood as resulting from the conflict between the
      necessity of filling space densely and uniformly and the tendency of unlike
      groups to be segregated spatially. The few other known structures of compounds
      with both (CF(2))(n) and (CH(2))(m) regions show evidence of the same conflict.

PMID- 15148438
TI  - Packing-dependent photochromism: the case of photoinduced intramolecular proton
      transfer in 6-(2',4'-dinitrobenzyl)-2,2'-bipyridine.
AB  - A new photoactive monoclinic polymorph (gamma-form) of 6-(2',4'-dinitrobenzyl)
      2,2'-bipyridine was obtained from an acetone-methanol solution. The crystal
      structure was compared with those of two polymorphs reported previously
      (photoactive orthorhombic alpha-form and photoinactive monoclinic beta-form) and
      with structures of related nitrobenzylpyridines to explain the relation between
      the structure and photochromism. The comparison of the reaction cavities around
      the reactive pyridyl-benzyl-nitro fragment among the polymorphs and related
      nitrobenzylpyridines revealed that a crucial factor for photochromic activity is
      the rotational freedom of the ortho-nitro group in their crystals and its
      accessibility from the proton-donor and proton-acceptor sites. This is because
      the ortho-nitro group should rotate around the N-C bond to transfer a proton from
      the methylene group to the N atom of the pyridine ring.

PMID- 15148439
TI  - Methods of crystallochemical analysis of supramolecular complexes by means of
      Voronoi-Dirichlet polyhedra: a study of cucurbituril host-guest compounds.
AB  - Crystallochemical analysis methods based on the Voronoi-Dirichlet partition of
      crystal space are extended to supramolecular complexes of any complexity. The
      sizes and shapes of receptor cavities and substrate molecules are shown to be
      successfully estimated as volumes and the second moments of inertia of the
      corresponding molecular Voronoi-Dirichlet polyhedra. To predict which organic
      substrates can occupy the receptor cavity a mini-expert system known as MOLVOL
      was created, comprising a database on completely determined crystal structures of
      almost 60000 organic molecular compounds. Using the developed methods, volumes
      and shapes are assessed for cucurbit[n]uril receptors (n = 5-10) and their
      cavities. A number of organic and inorganic molecules are found which can
      optimally fit the cavities inside the cucurbit[5]uril and cucurbit[6]uril
      molecules.

PMID- 15148440
TI  - The dynamics of the oxidant-antioxidant balance in the early phase of human acute
      biliary pancreatitis.
AB  - BACKGROUND/AIM: Reactive oxygen species play an important role in the
      pathogenesis of acute pancreatitis (AP) in animal models. Data on the oxidant
      antioxidant balance in humans are scanty. The present study was undertaken to
      evaluate the dynamics of changes in the oxidant-antioxidant balance in the early
      phase of human AP. METHODS: 74 consecutive patients with acute biliary
      pancreatitis (16 with severe, 58 with mild pancreatitis), treated endoscopically,
      were included in the study. Serum concentrations of sulfhydryl groups (SH; main
      nonenzymatic antioxidant; 73 patients) and thiobarbituric acid reactive
      substances (TBARS; markers of reactive oxygen species-mediated tissue damage; 56
      patients) were determined on admission and on each of 10 successive days. The
      analysis comprised the comparison of results in patients with mild and severe
      outcome of pancreatitis. RESULTS: Serum SH dropped by 27%, reaching the trough
      level on day 4 of hospitalization, whereas serum TBARS rose by 28%, reaching a
      peak 1 day later. Neither SH nor TBARS returned to initial values at the end of
      observation. The most dynamic changes in both SH and TBARS concentrations
      occurred in the first 3 days of hospitalization. The changes were significantly
      greater in patients with complicated pancreatitis in comparison to patients with
      mild disease, and were most pronounced in patients who developed infected
      pancreatic necrosis and who subsequently died. CONCLUSIONS: The oxidant
      antioxidant balance changes rapidly in the early phase of human AP, confirming
      the role of oxidative stress in the pathogenesis of AP. The degree of changes
      correlates with the clinical severity of pancreatitis.

PMID- 15148441
TI  - Chronic pancreatitis in the elderly in Japan.
AB  - BACKGROUND/AIM: Although the elderly comprise an increasingly large segment of
      the population, little has been written about chronic pancreatitis in this age
      group in Japan. In this study, we analyzed the clinical features of elderly
      Japanese patients with chronic pancreatitis and compared them with those of late
      onset chronic pancreatitis patients in Western countries. METHODS: Subjects were
      182 patients (162 males and 20 females) with chronic pancreatitis. They were
      divided into two groups: early-onset group (onset <65 years of age, n = 119) and
      late-onset group (onset > or =65 years of age, n = 63). Clinical findings and
      follow-up data were examined for each group. RESULTS: Alcohol abuse was the most
      common etiological factor in early-onset pancreatitis patients. In the late-onset
      group, the frequencies of idiopathic and autoimmune pancreatitis increased.
      Furthermore, the age at onset of autoimmune pancreatitis was >60 years in 94% of
      the cases. The late-onset group was more likely to have painless disease, and
      calcification of the pancreas and steatorrhea were rare in this group. Major
      causes of death were malignancy and malnutrition in each group. CONCLUSIONS:
      Early- and late-onset chronic pancreatitis showed different clinical features.
      Clinicians should consider autoimmune pancreatitis in the differential diagnosis
      in elderly patients with obstructive jaundice.

PMID- 15148442
TI  - Efficacy of lanreotide 30 mg on prevention of pain relapse after oral refeeding
      in patients with necrotizing acute pancreatitis. A phase II prospective
      multicentre study.
AB  - BACKGROUND: Pain relapse after oral refeeding occurs in 21% of the patients with
      acute pancreatitis, and in 35% of those with CT Balthazar's score > or =D [Gut
      1997;40:262]. Somatostatin analogues may decrease the pain relapse rate by
      inhibiting exocrine pancreatic secretion. AIMS, PATIENTS AND METHODS: To assess
      the frequency of pain relapse in patients with acute necrotizing pancreatitis
      after treatment with one intramuscular injection of lanreotide 30 mg on the day
      before refeeding. The refeeding procedure was standardized and progressive.
      RESULTS: 23 patients were included in 4 centres. Acute pancreatitis was alcoholic
      (n = 11), biliary (n = 7), other (n = 5). Twelve patients had > or =3 Ranson's
      criteria. Balthazar's score (1985) was D or E in 7 and 16 patients, respectively.
      Median duration of pain and of interruption of oral feeding were 11 (3-23) and 16
      (5-34) days, respectively. Median hospital stay was 22 (9-41) days. Only 1
      patient (4.3 %) had pain occurring 3 days after refeeding. CONCLUSION: Pain
      relapse occurred in 4.3% of patients pretreated with the somatostatin analogue
      lanreotide, and this figure is lower than the expected 35% rate which was
      previously reported without preventive treatment. This suggests that one
      intramuscular injection of lanreotide 30 mg on the day before refeeding could
      decrease pain relapse in patients with acute necrotizing pancreatitis, but has to
      be confirmed in a phase III study.

PMID- 15148443
TI  - Heterotopic pancreatitis with obstruction of the major duodenal papill--a rare
      trigger of obstructive orthotopic pancreatitis.
AB  - BACKGROUND: Heterotopic pancreas appears in 0.5 to 13% of autopsies. The most
      frequent locations are stomach, duodenum or upper jejunum. Pancreatitis in
      heterotopic pancreas is rarely described, and clinical symptoms caused by this
      heterotopic inflammation are uncommon. METHOD: We report a case of heterotopic
      pancreatitis localized in the major duodenal papilla causing biliary obstruction
      and mimicking a pancreatic head tumor. Clinically and radiologically, malignancy
      was suspected. Preoperative biopsies showed only fibrosis. A pylorus preserving
      resection of the pancreatic head was performed followed by an uneventful
      postoperative course. RESULT: Macroscopically, in the periampullary region on the
      pancreatic side a thickened duodenal wall with multiple lobules and cysts was
      found, compressing the common bile duct. Microscopic examination showed
      heterotopic pancreas with inflammatory lesions surrounding the ampulla. In the
      orthotopic pancreas a diffuse chronic pancreatitis with marked inflammation,
      fibrosis and atrophy of exocrine tissue was found. CONCLUSION: In our case it was
      impossible to differentiate between chronic pancreatitis and pancreas carcinoma
      preoperatively. Radiological findings and endoscopic biopsies were not sufficient
      to distinguish heterotopic pancreatitis from other tumors of the pancreatic head.
      Clear diagnosis could only be made by complete histological examinations after
      pancreatic head resection, being the treatment of choice for pancreatic head
      tumors of unclear dignity. The differential diagnosis of heterotopic pancreatitis
      as trigger of unclear enlargement of the pancreatic head is very seldom.

PMID- 15148444
TI  - The WayStation: the novel way for the collection of pancreatitis-associated
      mutations.

PMID- 15148445
TI  - NMDA receptors in the developing brain and effects of noxious insults.
AB  - This review covers normal expression of the NMDA receptor in the fetus and
      newborn, and then the response of the NMDA receptors within the central nervous
      system (CNS) during early development, to noxious stimuli. In the research
      setting, hypoxia is a commonly studied noxious stimulus that has been studied in
      a variety of contexts, including isolated hypoxia, or hypoxia combined with
      ischemia or hypercapnia, and delivered in single or repeated doses (intermittent
      stimuli). We review differences and commonalities between these experimental
      paradigms, and the sequelae of a common outcome, which is cell death, possibly
      through excitotoxic mechanisms. Finally, based on current literature, we will
      examine potential directions for clinical therapeutic interventions. By
      highlighting knowledge gaps in this field, we hope to encourage future research
      focusing on clinically relevant problems and outcomes in this area.

PMID- 15148446
TI  - Learning from NMDA receptor trafficking: clues to the development and maturation
      of glutamatergic synapses.
AB  - Activity-dependent changes in excitatory transmission allow the brain to develop,
      mature, learn and retain memories, and underlie many pathological states of the
      central nervous system. A principal mechanism by which neurons regulate
      excitatory transmission is by altering the number and composition of glutamate
      receptors at the postsynaptic plasma membrane. The dynamic trafficking of
      glutamate receptors to and from synaptic sites involves a complex series of
      events including receptor assembly, trafficking through secretory compartments,
      membrane insertion and endocytic cycling. While these events have become widely
      appreciated as critical processes regulating AMPA-type glutamate receptors during
      synaptic plasticity, the mechanisms that control the trafficking of NMDA-type
      glutamate receptors (NMDARs) are only now beginning to be understood. Until
      recently, NMDARs were considered immobile receptors, tightly anchored to the
      postsynaptic membrane. Here, we review recent evidence that challenges this view,
      focusing on the role that activity plays in altering NMDAR trafficking and how
      such dynamic regulation of NMDARs may impact on the plasticity of neural
      circuits.

PMID- 15148447
TI  - Translational regulation of the N-methyl-D-aspartate receptor subunit NR1.
AB  - Formation of functional N-methyl-D-aspartate (NMDA) receptor channels requires
      the essential NMDA receptor subunit NR1 and one or more of the modulatory
      subunits NR2A-D and in some cases an additional subunit NR3A or NR3B. Recent
      studies indicate that NR1 expression is regulated at translation under both
      physiological and pathological conditions. The rat pheochromocytoma cell line
      (PC12) has been used as a model system for NR1 gene expression studies.
      Characterization of the posttranscriptional regulatory mechanisms suggested the
      posttranslational degradation and translational regulation of NR1 protein in PC12
      cells. In addition a recent study on the translational regulation of NR1 mRNA in
      intact brain identified two translationally distinct pools of NR1 mRNA. In this
      review we summarize the evidence for translational regulation of NR1 expression
      in PC12 cells and the brain.

PMID- 15148448
TI  - Effects of mRNA untranslated regions on translational efficiency of NMDA receptor
      subunits.
AB  - Because NMDA receptors play critical roles in both neuronal survival and
      plasticity, their expression levels need to be carefully controlled. The number
      of functional NMDA receptors is temporally and spatially regulated at a hierarchy
      of levels, from gene transcription to protein trafficking. In this review we will
      focus on mechanisms for controlling functional expression of NMDA receptors that
      involve altering the efficacy of mRNA translation. One advantage of this level of
      control is that new receptors can be generated both rapidly and locally in
      response to appropriate synaptic activity patterns.

PMID- 15148449
TI  - Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of
      early-onset neonatal sepsis in preterm labor.
AB  - BACKGROUND: Our purpose was to determine whether amniotic fluid concentrations of
      tumor necrosis factor-alpha are of value in the prediction of early-onset
      neonatal sepsis (proven or suspected) in patients with preterm labor and intact
      membranes. METHODS: The relationship between amniotic fluid tumor necrosis factor
      alpha concentrations and early-onset neonatal sepsis was examined in 59
      consecutive patients with preterm labor and intact membranes who delivered
      preterm neonates within 72 h after transabdominal amniocentesis. Early-onset
      neonatal sepsis was defined either as the presence of a positive blood culture or
      as suspected sepsis within 72 h of delivery. Tumor necrosis factor-alpha was
      determined by enzyme-linked immunosorbent assays. RESULTS: Patients delivering
      neonates with early-onset neonatal sepsis had significantly higher median
      amniotic fluid TNF-alpha concentrations than patients delivering neonates without
      early-onset neonatal sepsis (p < 0.0005). An amniotic fluid tumor necrosis factor
      alpha concentration > or =41 pg/ml had a sensitivity of 82% (23/29) and
      specificity of 79% (38/48) in the prediction of early-onset neonatal sepsis.
      Multiple logistic regression indicated that elevated amniotic fluid tumor
      necrosis factor-alpha (> or =41 pg/ml) was the only independent predictor of
      early-onset neonatal sepsis (odds ratio 12.9, 95% confidence interval 1.3-125.3,
      p=0.01) after correction for known confounding variables. CONCLUSIONS: (1)
      Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of
      early-onset neonatal sepsis in patients with preterm labor and intact membranes.
      (2) Amniotic fluid tumor necrosis factor-alpha is a better independent predictor
      of early-onset neonatal sepsis than placental histologic finding or amniotic
      fluid culture.

PMID- 15148451
TI  - Vaginal Mullerian papilloma in a 2-year-old child.
AB  - Papillomas of the lower genital tract are rare benign lesions, which cause
      vaginal bleeding in girls. We report a case in a 2-year-old girl. Few cases have
      been described in children and adolescents. However, it should be considered as a
      possible diagnosis in girls with sanguineous vaginal discharge.

PMID- 15148450
TI  - Nasal bone measurement during the 1st trimester: is it useful?
AB  - The aim of this study was to present our preliminary data about nasal bone
      measurements at 11-14 weeks of pregnancy. This study was conducted in our
      prenatal unit between 2000 and 2003. A total of 642 pregnant women (single
      pregnancies) were enrolled into the study. During the first trimester of
      pregnancy, crown-rump length, nuchal translucency thickness, and fetal nasal bone
      length measurements and ductus venosus Doppler images were evaluated. The
      distribution of absent or small nasal bones in both normal fetuses and in those
      having some pathological conditions was compared by statistical analysis. p <
      0.05 was considered significant. Nasal bone evaluation was successful in 600 of
      642 (93.4%) ultrasound examinations. The linear regression line showed a
      significant positive slope with increasing crown-rump length (r=0.54, p < 0.001).
      Absent or small nasal bones were more common in abnormal than in normal fetuses
      (p=0.007). It is clear that the fetal nasal bone is becoming a powerful tool in
      prenatal screening for aneuploidy. Larger studies to be performed in a low-risk
      population are needed to assess whether the measurement of the nasal bone length
      provides additional benefits beyond the assessment of the presence or absence of
      the nasal bone.

PMID- 15148452
TI  - Continuous renal replacement therapy after cardiac surgery. Review of 85 cases.
AB  - BACKGROUND/AIMS: To evaluate the outcome of patients who require continuous renal
      replacement therapy (CRRT) following cardiac surgery. METHODS: All patients who
      received CRRT after cardiac surgery over more than 4 years at the Surgical
      Intensive Care Unit of the Montreal Heart Institute were reviewed. Among 5,564
      consecutive patients, 85 underwent CRRT postoperatively. RESULTS: The mean delay
      between surgery and CRRT initiation was 5 days, and the duration of CRRT was 9
      days, without a difference between survivors and non-survivors. Delivered
      clearances with CRRT were estimated at 25-28 ml/min (approximately 40
      liters/day), 29-32 ml/min (approximately 46 liters/day) and 17 ml/min
      (approximately 25 liters/day) for continuous veno-venous hemofiltration,
      continuous veno-venous hemodiafiltration and continuous veno-venous hemodialysis,
      respectively. In-hospital mortality was 43.5%. No difference in mortality was
      observed between patients with normal renal function at baseline and those with
      pre-operative renal dysfunction. Mortality was 33.3% after a coronary artery
      bypass graft (CABG), 57.1% after CABG and valve surgery, 60% after valve surgery,
      and 72.7% for redo-CABG or redo-valve surgery. 79% of survivors and 86% of non
      survivors had received a cardiopulmonary bypass (p = NS). The Simplified Acute
      Physiology Score II upon intensive care unit (ICU) admission and the requirement
      of an intra-aortic balloon pump were higher in non-survivors (p < 0.05). The mean
      length of ICU and hospital stay was 27.4 and 34.2 days for survivors and 17.9 and
      22.3 days for non-survivors, respectively (p < 0.05). CONCLUSIONS: Renal
      impairment is relatively common after cardiac surgery. The mortality of patients
      who required CRRT after cardiac surgery was 43.5% and was particularly influenced
      by the type of surgery.

PMID- 15148454
TI  - Protein loss in on-line hemofiltration.
AB  - BACKGROUND: The albumin serum level is one of the most important nutritional
      indices and is directly correlated to the uremic patient's hemodialysis outcome.
      One of the factors that can interfere with protein metabolism is the possible
      loss of albumin through the dialysis membrane that can contribute to keeping
      levels chronically low, especially for high-flux convective treatments requiring
      high permeability membranes and the removal of high volumes of plasma water.
      METHODS: Twenty stable patients undergoing chronic renal replacement therapy for
      at least 3 months were included. Each patient performed four hemofiltration
      treatments, 2 in post-dilution and 2 in pre-dilution (post-D, pre-D) with a
      polyamide membrane (Poliflux, 2.1 m2). RESULTS: The amount of albumin found in
      the ultrafiltrate was 2.9 +/- 1.5 g in post-D and 1.7 +/- 0.8 g in pre-D (p <
      0.01). Albumin loss during online HF was lower than 3 g per treatment, and
      significantly lower in pre-D than in post-D. Furthermore, we observed a
      correlation between the transmembrane pressure and the albumin loss in both
      techniques, but with different slopes (y = 0.351x - 10.014 in post-dilution and y
      = 0.0639x + 8.2403 in pre-dilution; p = 0.01): the same transmembrane pressure
      determines larger albumin losses in post-dilution than in pre-dilution.
      CONCLUSIONS: Convective treatments that utilize high exchange volume can be
      performed with no risk of a significant albumin loss, particularly in pre-D where
      the proteic component's contact with the dialysis membrane is lower. In post
      dilution the transmembrane pressure is a relevant factor in determining the
      protein loss.

PMID- 15148453
TI  - Effect of polymyxin B-immobilized fiber on blood metalloproteinase-9 and tissue
      inhibitor of metalloproteinase-1 levels in acute respiratory distress syndrome
      patients.
AB  - BACKGROUND/AIMS: Metalloproteinase (MMP)-9 plays a role in the pathogenesis of
      acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F)
      treatment improves circulatory disturbance and oxygenation in ARDS patients. We
      aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue
      inhibitor of MMP (TIMP)-1 levels in ARDS patients. METHODS: Twelve ARDS patients
      who received PMX-F treatment and 20 healthy control volunteers were included in
      this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a
      time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and
      after PMX-F treatment. We monitored blood pressure and the PaO2/FiO2 (PF) ratio
      before and after PMX-F treatment. RESULTS: The mortality of ARDS patients after
      PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in
      surviving patients after PMX-F treatment. Systolic and diastolic blood pressure
      increased significantly after PMX-F treatment (p < 0.01). The PF ratio also
      increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1
      levels in ARDS patients (126.4 +/- 36.4 and 326.5 +/- 52.5 ng/ml) were
      significantly higher than in controls (34.5 +/- 12.5 and 160.5 +/- 24.5 ng/ml; p
      < 0.01). PMX-F treatment reduced these levels significantly (the first treatment:
      MMP-9 85.4 +/- 28.6 ng/ml, p < 0.05, TIMP-1 265.8 +/- 36.6 ng/ml, p < 0.05; the
      second treatment: MMP-9 56.5 +/- 18.8 ng/ml, p < 0.01, TIMP-1 220.6 +/- 30.5
      ng/ml, p < 0.01). CONCLUSION: These data suggest that MMP-9 and TIMP-1 may play a
      role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased
      MMP-9 and TIMP-1 levels in ARDS patients.

PMID- 15148455
TI  - Continuous renal replacement technology: from adaptive technology and early
      dedicated machines towards flexible multipurpose machine platforms.

PMID- 15148456
TI  - Early cord clamping protects at-risk neonates from polycythemia.

PMID- 15148458
TI  - Effect of hyaluronan-supplemented dialysate on in vitro function of human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Addition of hyaluronan (HA) to the dialysis solution has been
      suggested as a means to protect the peritoneum from injury during peritoneal
      dialysis (PD). METHODS: Concentrations of inflammatory mediators were determined
      in dialysate samples obtained from PD patients after 6-hour dwells with glucose
      based (13.6 g/l) solution containing 0.1 and 0.5 g/l of exogenous high-molecular
      weight HA. We additionally evaluated the effect of HA-supplemented dialysate,
      drained after dwell in PD patients, on function of human peritoneal mesothelial
      cells (MC) in in vitro culture. RESULTS: Concentration of nitrites was
      significantly higher in HA 0.5 g/l supplemented dialysate (+43%, p < 0.05) as
      compared to control. Levels of monocyte chemoattractant protein (MCP-1), soluble
      intercellular adhesive molecule (s-ICAM), vascular endothelial growth factor
      (VEGF) and fibronectin were comparable in all the studied groups. However, when
      MC were exposed in in vitro conditions for 24 h to the studied dialysates, we
      observed that HA containing fluids inhibited the synthesis of MCP-1, s-ICAM, VEGF
      and fibronectin in these cells. HA-supplemented dialysate accelerated growth rate
      of in vitro proliferating MC. CONCLUSION: High-molecular-weight HA added to the
      dialysis fluid exerts anti-inflammatory and antifibrotic actions on the in vitro
      cultured MC and accelerates their growth rate what may be important for
      peritoneal healing during PD.

PMID- 15148457
TI  - Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for
      cisplatin nephrotoxicity.
AB  - BACKGROUND: Cisplatin is one of the most widely used chemotherapeutic agents, but
      the risk of nephrotoxicity frequently hinders the use of higher doses to maximize
      its antineoplastic effects. The lack of early biomarkers has impaired our ability
      to initiate potential therapeutic or preventive interventions in cisplatin
      nephrotoxicity in a timely manner. In this study, we have explored the expression
      and urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in a
      mouse model of cisplatin-induced nephrotoxic injury. METHODS: Mice were subjected
      to intraperitoneal injections of 20 mg/kg (high dose) or 5 mg/kg (low dose)
      cisplatin. The expression of NGAL was measured in the kidney and urine by Western
      analysis and immunofluorescence, and compared to changes in serum creatinine and
      urinary N-acetyl-beta-D-glucosaminidase (NAG). RESULTS: Cisplatin resulted in
      tubule cell necrosis and apoptosis following the high dose, but not the low dose.
      By Western analysis, NGAL protein was rapidly induced in the kidney within 3 h of
      high-dose cisplatin. By immunofluorescence, NGAL was induced predominantly in
      proximal tubule cells in a punctate cytoplasmic distribution, reminiscent of a
      secreted protein. NGAL was easily detected in the urine by Western analysis
      within 3 h of cisplatin administration in a dose- and duration-dependent manner.
      By comparison, changes in urinary NAG or serum creatinine were not evident until
      96 h after cisplatin. Using defined concentrations of purified recombinant NGAL,
      urinary NGAL excretion following cisplatin administration was quantified to be in
      the 20-80 ng/ml range. CONCLUSION: The results indicate that NGAL represents an
      early and quantitative urinary biomarker for cisplatin nephrotoxicity.

PMID- 15148459
TI  - Angiotensin II type 1 and type 2 receptors reciprocally modulate pro
      inflammatory/ pro-fibrotic reactions in activated splenic lymphocytes.
AB  - Angiotensin II (Ang II) type 1 receptor (AT1R) has been confirmed to confer
      renoprotection in the progressive, immune-mediated nephritis in animal models as
      well as in humans. However, the relative contributions of direct AT1R blockade,
      indirect counteractivation of Ang II type 2 receptor (AT2R), or both, to
      renoprotection through AT1R antagonism remains to be clarified.
      Immunohistochemical studies in the nephritic kidney revealed that tubular
      epithelial cells and infiltrating immune cells were positive for AT1R and AT2R.
      In the present study, we investigated the action of Ang II on both receptors on
      immune cells. A subpopulation of lipopolysaccharide-activated splenic lymphocytes
      (mixed lymphocyte populations) was positive for AT1R and AT2R. Ang II alone could
      not induce gene expression of a pro-inflammatory chemokine JE or a pro-fibrotic
      cytokine transforming growth factor-beta1 in those cells. However, Ang II could
      significantly suppress the expression of both genes in those cells under AT1R
      blockade, and this action was mediated through AT2R. Conversely, the pro
      inflammatory/pro-fibrotic gene expression could be enhanced by AT2R blockade, and
      this was mediated through AT1R. AT1R and AT2R expressed in activated immune cells
      can modulate pro-inflammatory and pro-fibrotic reactions reciprocally. In
      advanced immune-mediated nephritic kidneys, AT1R antagonism likely confers
      renoprotection via activation of AT2R.

PMID- 15148460
TI  - Original research published in the chiropractic literature: evaluation of the
      research report.
AB  - OBJECTIVE: To evaluate the quality of research reports published in the
      chiropractic literature. Data Sources Original research articles, defined as
      those reporting studies that included primary data collection, published in the
      13 Chiropractic Research Journal Editors Council member journals from January
      1999 through February 2000. METHODS: A 2-page checklist developed from review
      criteria used in the biomedical literature. Three doctoral-trained
      biostatisticians blinded to author identification and affiliation evaluated the
      articles. RESULTS: Of the 73 eligible articles, 21% lacked description of the
      study design, 77% did not provide a sample size justification, 26% reported
      inappropriate descriptive statistics, 26% reported conclusions not supported by
      the results, and 21% did not avoid redundancy of information presented in tables,
      figures, and text. Of the 55 articles with a primary objective of testing, 10 did
      not report any inferential statistics, 19 reported inappropriate inferential
      statistics, and 22 did not make the primary comparisons of interest clear.
      CONCLUSIONS: In this study, we evaluated the quality of the research report
      rather than the research itself. However, the value of the research articles is
      diminished by the poor quality of reporting, as well as the actual errors in data
      analysis. Yet, this problem is not unique to the chiropractic literature. It is
      recommended that all investigators submitting manuscripts to chiropractic
      journals use available guidelines in preparing their research reports and that
      reviewers use those same guidelines in critiquing the manuscripts.

PMID- 15148461
TI  - Active trunk extensor contributions to dynamic posteroanterior lumbar spinal
      stiffness.
AB  - BACKGROUND: Assessments of posteroanterior (PA) spinal stiffness using
      mobilization apparatuses have demonstrated an increase in PA spine stiffness
      during voluntary contraction of the lumbar extensor muscles; yet, little work has
      been done to this degree in symptomatic subjects. OBJECTIVE: To use a previously
      validated dynamic mechanical impedance procedure to quantify changes in PA
      dynamic spinal stiffness at rest and during lumbar isotonic extension tasks in
      patients with low back pain (LBP). METHODS: Thirteen patients with LBP underwent
      a dynamic spinal stiffness assessment in the prone-resting position and again
      during lumbar extensor efforts. Stiffness assessments were obtained using a
      handheld impulsive mechanical device equipped with an impedance head (load cell
      and accelerometer). PA manipulative thrusts (approximately 150 N, <5
      milliseconds) were delivered to skin overlying the L3 left and right transverse
      processes (TPs) and to the L3 spinous process (SP) in a predefined order (left
      TP, SP, right TP) while patients were at rest and again during prone-lying lumbar
      isotonic extension tasks. Dynamic spinal stiffness characteristics were
      determined from force and acceleration measurements using the apparent mass (peak
      force/peak acceleration, kg). Apparent mass measurements for the resting and
      active lumbar isotonic task trials of each patient were compared using a 2
      tailed, paired t test. RESULTS: A significant increase in the PA dynamic spinal
      stiffness was noted for thrusts over the SP (apparent mass [17.0%], P=.0004)
      during isotonic trunk extension tasks compared with prone resting, but no
      statistically significant changes in apparent mass were noted for the same
      measures over the TPs. CONCLUSIONS: These findings add support to the
      significance of the trunk musculature and spinal posture in providing increased
      spinal stability.

PMID- 15148462
TI  - Low back pain in Australian adults: prevalence and associated disability.
AB  - OBJECTIVES: To determine the prevalence ranges of low back pain (LBP) together
      with any related disability in Australian adults. DESIGN: A population-based
      survey. METHODS: The survey was mailed in June 2001 to a stratified random sample
      of 3000 Australian adults selected from the Electoral Roll. Demographic variables
      of respondents were compared with the Australian population. Selective response
      bias was investigated using wave analysis. A range of prevalence data was
      derived, as were disability scores using the Chronic Pain Grade. RESULTS: There
      was a 69% response rate. There was little variation between the sample and the
      Australian adult population. There was no significant selective response bias
      found. The sample point prevalence was estimated at 25.6% (95% confidence
      interval [CI], 23.6-27.5), 12-month prevalence was 67.6% (95% CI, 65.5-69.7), and
      lifetime prevalence was 79.2%, (95% CI, 77.3-81.0). In the previous 6-month
      period, 42.6% (95% CI, 40.4-44.8) of the adult population had experienced low
      intensity pain and low disability from it. Another 10.9% (95% CI, 9.6-12.3) had
      experienced high intensity-pain but still low disability from this pain. However,
      10.5% (95% CI, 9.2-11.9) had experienced high-disability LBP. CONCLUSION: LBP is
      a common problem in the Australian adult population, yet most of this is low
      intensity and low-disability pain. Nevertheless, over 10% had been significantly
      disabled by LBP in the past 6 months. Data from this study will provide a better
      understanding of the magnitude of the LBP problem in Australia, the need for
      access to health care resources, and also strategic research directions.

PMID- 15148463
TI  - Interprofessional collaboration and job satisfaction of chiropractic physicians.
AB  - BACKGROUND: Despite the fact that chiropractic physicians (DCs) are growing in
      number and legitimacy in the community of health care professionals, little
      recent research describes how their relationships with medical doctors (MDs)
      affect their job and career perceptions. OBJECTIVE: This study explores
      interprofessional relations by identifying factors associated with variations in
      how DCs evaluate their interaction with MDs. It also adapts a previously
      validated multifaceted measure of MD job satisfaction for use with DCs. DESIGN:
      Cross-sectional survey of 311 DC physicians in North Carolina. RESULTS: The
      hypothesized multifaceted nature of DC job satisfaction was confirmed. Four
      distinct job facets and global career satisfaction were measured effectively in
      DCs. DCs' career satisfaction is related to satisfaction with compensation,
      intrinsic motivation of relating to patients, and having positive relationships
      with DC colleagues. DCs report referring patients to MDs more often than they
      report MDs referring patients to them. Satisfaction with relationships between
      DCs and MDs is relatively low and is strongly linked to the quantity of referrals
      from MDs and the perception that MDs practice collaboratively with DCs. However,
      DCs' global career satisfaction is unrelated to their relationships with MDs.
      CONCLUSION: Global career satisfaction of DCs is relatively high and unaffected
      by the low level of satisfaction DCs report having with their relationships with
      MDs. These findings suggest that despite increasing interaction and
      interdependence, DCs' relationship with MDs is of minor importance in their
      professional self-image.

PMID- 15148465
TI  - Prescribing wellness: a case study exploring the use of health information
      brochures.
AB  - OBJECTIVE: A case study was undertaken to ascertain the potential usefulness of
      brochures as a strategy for encouraging short-term and longer-term acquisition of
      healthy behaviors at the consumer-health care system interface. METHOD: Purposive
      sampling of chiropractic clinics and convenience sampling of patients attending
      these primary contact practitioners were undertaken. Patients were asked to
      complete a questionnaire. Interested patients were given a health information
      brochure on topics of their choice. Patients who had requested health information
      brochures were phoned at 3 weeks, 3 months, and 1 year after completing the
      initial questionnaire and asked if they had implemented any of the suggestions
      for health promotion or risk prevention. A minimum of 4 attempts were made to
      contact each participant by telephone. Data were analyzed using descriptive
      statistics. RESULTS: Twenty-one chiropractic clinics and 781 patients
      participated. Although every third patient requested one or more health
      information brochures, fewer than 1 in 4 of those receiving brochures implemented
      some health-promoting behavior. Although some patients persisted with their newly
      initiated health-promoting behaviors, compliance diminished over time. Exercise
      and dietary change were the behaviors most likely to be modified. CONCLUSION:
      Implementation of even one healthy behavior can have a ubiquitous health benefit.
      Despite dwindling compliance, it is therefore suggested that suitably formulated
      health information brochures that inform and encourage adoption of healthy
      behaviors by motivated patients deserve consideration by all health professionals
      working at the consumer-health care system interface.

PMID- 15148464
TI  - Applying evidence-based health care to musculoskeletal patients as an educational
      strategy for chiropractic interns (a one-group pretest-posttest study).
AB  - OBJECTIVE: To describe and measure the effectiveness of a problem-based
      educational strategy for teaching evidence-based health care (EBHC) to
      chiropractic interns, which focused on the development and appraisal of
      answerable clinical questions using actual musculoskeletal patients. METHODS: A 1
      group pretest-posttest design (simple panel design) with investigator-blinded
      survey administration was used to measure effectiveness of educational activities
      using adult learning theory with a study population of interns (n=31) at a
      chiropractic college (Los Angeles College of Chiropractic, Southern California
      University of Health Sciences [LACC/SCUHS]) teaching clinic. Activities included
      2 workshops on constructing clinical questions and critical appraisal of
      published research and independent patient-based EBHC assignments. A qualitative
      self-assessment survey was administered before and after a 6-week period of EBHC
      activities to measure their effectiveness. Sign tests and paired t tests were
      utilized to determine P values for significant difference of score results.
      RESULTS: Eighty-one percent of subjects completed the pretest-posttest surveys.
      All survey item responses showed an average increase in subjects' self-rating of
      skills and attitudes from pretest to posttest. There were statistically
      significant differences in interns' self-assessed ability to construct an
      answerable clinical question and appraise research articles and apply them to
      patient management, as well as their rating of importance of EBHC in patient
      decision making. CONCLUSIONS: The results of this study suggest that having
      chiropractic interns apply EBHC to actual musculoskeletal patients along with
      attending EBHC workshops had a positive impact on interns' perceived ability to
      practice EBHC.

PMID- 15148466
TI  - Paraspinal muscles and intervertebral dysfunction: part one.
AB  - BACKGROUND: One of the diagnostic characteristics of the manipulable spinal
      lesion--a musculoskeletal disturbance detected by manual palpation and corrected
      with manipulation--is said to be altered segmental tissue texture. Various manual
      therapy authors have speculated on the possible nature of this tissue change,
      with some authors hypothesizing that it represents deep segmental muscle
      overactivity. OBJECTIVES: To review the literature relating to the detection and
      nature of altered paraspinal tissue texture, proposed explanations for altered
      tissue texture, evidence for the plausibility of paraspinal muscle spasm, and
      evidence of muscle dysfunction associated with low back pain (LBP). DATA SOURCE:
      MEDLINE and CINAHL databases were searched using various combinations of the
      keywords paraspinal, muscle, palpation, EMG, spine, low back pain, pain,
      myofascial, hardness, manipulation, reliability, and somatic dysfunction, along
      with searching the bibliographies of selected articles and textbooks. DATA
      EXTRACTION: All relevant data were used. RESULTS: Little direct evidence exists
      for the nature of abnormal paraspinal tissue texture detected by palpation.
      Palpation for tenderness is more reliable than palpation for tissue texture
      change. Indirect evidence from animal studies and experimental muscle
      inflammation support the plausibility of protective paraspinal muscle
      contraction. Increased paraspinal electromyographic (EMG) activity observed in
      subjects with LBP appears to be a result of voluntary and nonvoluntary changes in
      motor control, modified by psychophysiological responses to perceived stress
      rather than a simple protective reflex. CONCLUSION: Although little direct
      evidence exists of the nature of clinically detected paraspinal tissue texture
      change, the concept of reactive muscle contraction appears plausible. Increased
      paraspinal EMG activity associated with LBP does not appear to be mediated by a
      simple protective reflex.

PMID- 15148467
TI  - Bilateral acrometastasis secondary to breast cancer.
AB  - BACKGROUND: One out of every 8 women will be diagnosed with breast cancer and 1
      in 28 will succumb to the disease. Skeletal metastasis occurs in 16% to 73% of
      breast cancer patients. OBJECTIVE: To present a comprehensive look at the
      pathophysiology, clinical presentation, and treatment options for skeletal
      metastasis secondary to breast carcinoma by discussing the case of an 80-year-old
      female patient with bilateral distal lower extremity metastasis following a
      previous diagnosis of breast cancer. CLINICAL FEATURES: The patient had severe
      pain in both lower extremities, which caused her to have difficulty when
      ambulating. She also complained of fatigue and anorexia, with an 8-lb weight
      loss. Chest examination revealed widespread rales without change. Her left
      calcaneus was tender to palpation and both feet and ankles were hot and swollen.
      Laboratory CA 27.29 values were 1131 on October 16, 2001, which was elevated
      compared with the 454 value obtained previously. Plain films of the lower
      extremities revealed destructive lesions of the distal left and right tibia and
      fibula with involvement of the left calcaneus. These findings were most
      consistent with metastasis. INTERVENTION AND OUTCOME: The patient refused further
      care and sought a hospice referral. CONCLUSION: There is no cure for
      acrometastasis and prognosis is poor. Treatment focuses on symptomatic relief,
      extended survival, and maintaining quality of life. Clinicians should consider
      metastasis in a patient with distal lower extremity osteolytic lesions with a
      previous history of breast malignancy.

PMID- 15148468
TI  - Chiropractic management of Ehlers-Danlos syndrome: a report of two cases.

PMID- 15148469
TI  - Chiropractic management of patients with bilateral congenital hip dislocation
      with chronic low back and leg pain.
AB  - OBJECTIVE: To discuss conservative methods for treating patients with chronic low
      back and leg pain associated with the biomechanical and postural alterations
      related to bilateral congenital hip dislocation. CLINICAL FEATURES: This report
      describes the cases of 2 adult female subjects with bilateral congenital hip
      dislocation without acetabula formation who suffered from chronic low back and
      leg pain managed conservatively by chiropractic methods. The first subject is a
      45-year-old woman with a 9-month history of right buttock pain and radiating
      right leg pain and paresthesia down to the first 2 toes, with a diagnosis of a
      herniated L4 intervertebral disk. The second subject is a 53-year-old woman who
      complained of chronic intermittent low back pain and constant unremitting pain on
      her right leg for the last 3 years. INTERVENTION AND OUTCOME: Chiropractic
      manipulation utilizing Logan Basic apex and double notch contacts, as well as
      sacroiliac manipulation on a drop table with a sacrum contact and with a
      posterior to anterior and superior to inferior (PA-SI) rocking thrust, together
      with a spinal stabilization exercise program, were used on these 2 patients. Both
      patients had significant clinical improvement, with reduction on the Visual
      Analogue Scale (VAS) of 67% and 84%, Oswestry Disability Index improvement of 73%
      and 81%, and an improvement on the Harris hip score of 71% and 44%, respectively.
      CONCLUSION: A conservative management approach, including specific chiropractic
      manipulation and a spinal stabilization exercise program, can help manage the
      treatment of adult patients with chronic low back and leg pain related to
      bilateral congenital dislocation of the hips.

PMID- 15148472
TI  - Bombing of the U.N. building in Baghdad.

PMID- 15148471
TI  - Heavy metal search & care missions.

PMID- 15148474
TI  - That just broke my little heart...

PMID- 15148476
TI  - Who gets to ride? Deciding when it's appropriate not to transport patients to the
      ED.

PMID- 15148477
TI  - A very public partnership: how REMSA is tuned in & improving EMS public
      perception, one injury-prevention program at a time.

PMID- 15148478
TI  - Primary blast injury: an EMS guide to pathophysiology, assessment & management.

PMID- 15148479
TI  - Suicide bomber response.

PMID- 15148480
TI  - Motorsports EMS: an emerging subspecialty.

PMID- 15148482
TI  - Traumatic hand injuries: getting a grip on prehospital hand trauma assessment &
      management.

PMID- 15148483
TI  - A stretcher to meet your biggest needs.

PMID- 15148481
TI  - No-fly zones: Hillsborough County defines urban grids where ground transport of
      trauma patients makes the most sense.

PMID- 15148485
TI  - Network eyes.

PMID- 15148486
TI  - Once upon a medic's time.

PMID- 15148487
TI  - Nicotine nightmare.

PMID- 15148488
TI  - High school students save small-town ambulance service.

PMID- 15148489
TI  - Significance of selectively targeted apoptotic rete cells in graft-versus-host
      disease.
AB  - Considerable data exist regarding the mechanisms of allostimulation and homing
      (the effector phases) in graft-versus-host disease (GVHD). Current dogma suggests
      that target specificity involves preferential injury to epithelial surfaces of
      the skin and squamous mucosae, liver, and gut. Little attention has been devoted,
      however, to mechanisms of cellular targeting or to whether heterogeneity exists
      in target tissues with regard to a threshold for cellular injury. A recent
      breakthrough in understanding the target stage of GVHD indicates that the
      predominant pathway of injury to squamous epithelial cells involves apoptosis.
      Moreover, apoptotic injury may be associated or unassociated with local T-cell
      infiltration and involves phenotypically and antigenically distinctive epithelial
      cells within the basal layer of the skin and squamous mucosa. These cells are
      confined to rete ridges in the skin and retelike prominences in the dorsal tongue
      and are designated as selectively targeted apoptotic rete (STAR) cells. The
      discovery of STAR cells in GVHD paves the way for speculation and experimentation
      to determine why these subpopulations are selectively vulnerable and how soluble
      and cellular effectors of apoptosis contribute to their ultimate demise. Novel
      approaches to GVHD treatment derived from understanding mechanisms of selective
      epithelial injury are likely to use strategies to render target cells less
      susceptible to the apoptosis that is ultimately responsible for organ dysfunction
      and failure.

PMID- 15148490
TI  - Graft-versus-host disease of the skin: life and death on the epidermal edge.
AB  - Despite impressive advances in the field of allogeneic hematopoietic
      transplantation, graft versus host disease (GVHD) remains a significant obstacle
      to be overcome; it would enhance the safety and efficacy of this life-saving
      therapy. This review provides a framework for understanding the molecular and
      cellular basis underlying GVHD. We propose a 3-phase model of GVHD that
      highlights the importance of the conditioning regimen on the recipient tissues
      administered prior to infusion of donor bone marrow inoculum. A novel skin
      explant model, designed to take into consideration the immunobiological
      consequences of conditioning regimens on resident host cells, is proposed to
      advance our understanding of GVHD and serve as a potential prognostic tool when
      allogeneic recipient/donor combinations are being contemplated in the clinic.
      Within this review, specific emphasis is placed on the importance of defining the
      apoptotic machinery engaged in epidermal keratinocytes triggered by both
      conditioning regimens, and by host resident and recruited immunocytes and soluble
      mediators produced at sites of injury. The review is completed with a working
      model for cutaneous GVHD. Although the skin is highlighted because of its
      accessibility for clinical observations and serial sampling opportunities,
      lessons learned from studies of cutaneous GVHD are likely to provide valuable
      insights into GVHD occurring in the gastrointestinal tract, lung, and liver. With
      new insights designed to better predict and prevent GVHD and novel agents
      designed to treat GVHD, overcoming this current impediment to successful bone
      marrow transplantation should become increasingly feasible.

PMID- 15148491
TI  - Chronic graft-versus-host disease after granulocyte colony-stimulating factor
      mobilized allogeneic stem cell transplantation: the role of donor T-cell dose and
      differentiation.
AB  - The use of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral
      blood as a source of stem cells has resulted in a high incidence of severe
      chronic graft-versus-host disease (cGVHD), which compromises the outcome of
      clinical allogeneic stem cell transplantation. We have studied the effect of G
      CSF on both immune complex and fibrotic cGVHD directed to major (DBA/2 -->
      B6D2F1) or minor (B10.D2 --> BALB/c) histocompatibility antigens. In both models,
      donor pretreatment with G-CSF reduced cGVHD mortality in association with type 2
      differentiation. However, after escalation of the donor T-cell dose, scleroderma
      occurred in 90% of the recipients of grafts from G-CSF-treated donors. In
      contrast, only 11% of the recipients of control grafts developed scleroderma, and
      the severity of hepatic cGVHD was also reduced. Mixing studies confirmed that in
      the presence of high donor T-cell doses, the severity of scleroderma was
      determined by the non-T-cell fraction of grafts from G-CSF-treated donors. These
      data confirm that the induction of cGVHD after donor treatment with G-CSF is
      dependent on the transfer of large numbers of donor T cells in conjunction with a
      putatively expanded myeloid lineage, providing a further rationale for the
      limitation of cell dose in allogeneic stem cell transplantation.

PMID- 15148492
TI  - Phase II study of autologous transplantation with interleukin-2-incubated
      peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or
      refractory non-Hodgkin lymphoma.
AB  - Previous work suggested that interleukin (IL)-2 can be used for eradicating
      residual disease in autologous grafts and for preventing recurrence. We report a
      phase II study of autologous peripheral blood stem cell transplantation with in
      vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2
      in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage
      chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent
      autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells
      were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four
      monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to
      5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients
      were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2
      incubated stem cells. The average received dose of posttransplantation IL-2 was
      30% to 50% of planned. Only 42 patients received maintenance IL-2. The average
      received maintenance dose of IL-2 was also approximately 30% of planned. Most
      dose reductions were due to toxicity or patient refusal. Three-year survival and
      progression-free survival for all registered patients were 43% (95% confidence
      interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60
      patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95%
      CI, 31%-57%), respectively. There was no relation between the dose of IL-2
      received and outcome. Survival and disease-free survival of the study group were
      similar to those of a previous study cohort that received unmanipulated stem
      cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood
      stem cells and intensive posttransplantation IL-2 was associated with
      considerable but rapidly reversible toxicity. No effect on long-term outcome was
      observed.

PMID- 15148493
TI  - Randomized comparison of granulocyte colony-stimulating factor versus granulocyte
      macrophage colony-stimulating factor plus intensive chemotherapy for peripheral
      blood stem cell mobilization and autologous transplantation in multiple myeloma.
AB  - Autologous peripheral blood stem cell transplantation for multiple myeloma offers
      higher response rates and improved survival compared with conventional
      chemotherapy. However, successful autografting requires effective cytoreduction
      and rapid hematologic reconstitution. We conducted a prospective randomized
      clinical trial to assess the efficacy of 2 cycles of priming chemotherapy with
      either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) for peripheral blood stem cell mobilization
      followed by autologous transplantation. The major study end points were the
      comparative utility of G-CSF versus GM-CSF, the percentage of patients achieving
      complete response after transplantation, and overall and progression-free
      survival. Priming chemotherapy included cyclophosphamide (4 g/m2), mitoxantrone
      (8 g/m2 every day for 2 days), and dexamethasone (20 mg/m2 every 12 hours for 2
      days) followed by randomization to either G-CSF or GM-CSF daily until completion
      of leukapheresis. Conditioning for transplantation included cyclophosphamide (75
      mg/kg every day for 2 days) plus total body irradiation (165 cGy twice daily for
      3 days), and patients received maintenance immunotherapy with interferon alpha.
      Seventy-two patients were randomized, and 64 underwent autologous
      transplantation. The median age at transplantation was 52 years, and the median
      time from diagnosis to transplantation was 10 months; 58% of the patients had
      received >4 cycles of pretransplantation chemotherapy. The median number of CD34+
      cells obtained after mobilization was 16.4 x 10(6)/kg in the G-CSF arm versus
      12.8 x 10(6)/kg in the GM-CSF arm (P = .8). Neutrophil recovery was faster in the
      G-CSF group after both cycle 1 (median, 13 days with G-CSF and 16 days with GM
      CSF; P < .01) and cycle 2 (median, 13 days versus 17 days in the 2 groups,
      respectively; P = .03). Although platelet recovery was similar after cycle 1,
      platelet recovery to >100000/microL was notably faster in the G-CSF group both
      after cycle 2 and after transplantation (P = .03). Response and overall and
      disease-free survival were similar in both cohorts. Overall, 23% of the patients
      achieved a complete response after priming chemotherapy, which improved to 33%
      after transplantation. An additional 47% attained a partial response after
      transplantation, for a total response rate of 80%. With a median follow-up of 2
      years (range, 0.7-8 years), the overall survival was 88% (95% confidence interval
      [CI], 80%-96%) at 1 year and 65% (95% CI, 51%-79%) at 3 years. Progression-free
      survival was 73% (95% CI, 62%-84%) at 1 year and 40% (95% CI, 26%-54%) at 3
      years. Relapse or progressive disease was the most common cause of death (25
      [83%] of 30 deaths). We conclude that mobilization with chemotherapy plus G-CSF
      versus GM-CSF results in similar CD34+ progenitor collections, even in patients
      exposed to multiple cycles of alkylator-based chemotherapy. Earlier neutrophil
      and platelet recovery was seen with G-CSF priming. Two cycles of priming
      chemotherapy plus autologous transplantation yields survival rates similar to
      those in published reports, including those using tandem transplantation.

PMID- 15148494
TI  - An evaluation of the donor experience in the canadian multicenter randomized
      trial of bone marrow versus peripheral blood allografting.
AB  - We compared the donation of bone marrow (BM) versus recombinant human granulocyte
      colony-stimulating factor-mobilized peripheral blood progenitor cells (PBPC) in
      HLA-matched sibling donors. Donors randomized to donate BM or PBPC completed
      questionnaires (Profile of Mood States [POMS] and Short-Form 36 Health Survey)
      assessing peridonation health-related quality of life (QoL), donation experience,
      and acceptability of donation before and 1 week and 4 weeks after donation.
      Between January 1996 and March 1999, 184 patients and their donors were
      randomized. Predonation and postdonation data were available on 52 (56%) and 35
      (38%) of the BM and PBPC donors, respectively. The median donor age was 45 years,
      and 44% were female. The median time (range) to return to full activity for the
      BM and PBPC donors was 4 days (1-21 days) and 2 days (0-21 days), respectively (P
      = .01). One week after donation, BM donors reported more fatigue and less energy
      than the PBPC donors. BM donors' POMS total mood disturbance scores were worse 1
      week after versus before donation, whereas the PBPC donors' scores did not
      change. POMS subscores indicated more fatigue and less energy in the BM versus
      PBPC donors. Anxiety improved in both groups, but more in PBPC donors. Four weeks
      after donation, the Short-Form 36 Health Survey indicated persistent moderate
      negative effects on QoL with BM donation versus small effects with PBPC donation.
      BM donation was associated with more physical morbidity and negative effects on
      QoL up to 1 month after donation than was PBPC donation. Despite this, most
      donors would donate again. Further work is needed to decrease donor anxiety and
      symptoms. If both BM and PBPC donation are feasible, then the graft source should
      be dictated by the predicted patient outcome as determined from the results of
      randomized trials.

PMID- 15148495
TI  - Prognostic significance of occult tumor cells in the apheresis products of
      patients with advanced breast cancer receiving high-dose chemotherapy and
      autologous hematopoietic progenitor cell support.
AB  - We prospectively evaluated the prognostic significance of occult tumor cells
      (OTCs) contaminating the peripheral blood progenitor cell apheresis products of
      patients with advanced breast cancer receiving high-dose chemotherapy.
      Immunocytochemistry of peripheral blood progenitor cells was performed in 242
      patients with high-risk primary breast cancer (HRPBC) and in 111 patients with
      metastatic breast cancer (MBC). OTCs were detected in 6.6% of HRPBC patients and
      in 16.2% of MBC patients (P = .005). In HRPBC, OTCs correlated with worse
      prognostic scores and larger tumor sizes, but not with axillary nodal status,
      hormone receptors, or HER2. In the MBC group, OTCs correlated with bone marrow
      involvement and with disease status at transplantation. The number of apheresis
      procedures was not associated with the risk of contamination. In HRPBC patients,
      at a median follow-up of 7 years (range, 1.5-11 years), the presence of OTCs
      correlated with worse event-free survival (P = .007) and overall survival (P =
      .002). In the MBC group, OTCs correlated with worse event-free survival (P =
      .04), but not overall survival (P = .2). In multivariate analyses, the presence
      of OTCs had an independent adverse effect on outcome in HRPBC, but not MBC. Our
      observations imply a direct role of OTCs in posttransplantation relapse in HRPBC.

PMID- 15148501
TI  - The effects of a 5-hydroxytryptamine 1A receptor gene polymorphism on the
      clinical response to fluvoxamine in depressed patients.
AB  - We investigated the effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene
      polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed
      outpatients who gave written consent to participate in the study. Patients
      visited every 2 weeks after the first examination until the week 12 end point and
      were evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at
      each visit. FLV dose was changed in response to their clinical symptoms. The
      Gly272Asp polymorphism of the 5-HT1A receptor gene was identified by a PCR
      method. The subjects with the Asp allele had a significantly higher % reduction
      in the HAM-D-17 score than those with the Gly/Gly genotype at week 2 (P=0.009),
      week 6 (P=0.036), and week 12 (P=0.031). There was a significant difference in
      the genotype distribution between the responders and nonresponders. These results
      suggest that the Gly272Asp polymorphism of the 5-HT1A receptor gene may predict
      the response to FLV.

PMID- 15148502
TI  - The genetics of vitamin K antagonists.

PMID- 15148503
TI  - Gliosarcoma with epithelial differentiation: immunohistochemical and molecular
      characterization. A case report and review of the literature.
AB  - Few reported cases of gliosarcomas or glioblastomas with epithelial-like areas
      exist. Most cases were originally diagnosed as metastatic carcinoma. Focal
      expression of glial fibrillary acidic protein has helped characterize these
      tumors as having a glial origin. We report a case of gliosarcoma with multifocal,
      extensive areas of well-differentiated carcinoma; demonstrating squamous and
      glandular differentiation. The expression of glial fibrillary acidic protein and
      epithelial phenotype were mutually exclusive. We performed extensive
      immunohistochemical analyses and comparative genotypic analysis using
      microdissection to secure representative glial and epithelial components. Loss of
      heterozygosity was analyzed with a panel of 12 polymorphic microsatellite markers
      designed to indicate allelic loss and situated in proximity to known tumor
      suppressor genes located on chromosomes 1p, 9p, 10q, 17p and 19q. We found
      comparable patterns of acquired allelic loss between the glial and carcinomatous
      components, strongly supporting the monoclonal origin of this neoplasm. This case
      represents an extreme form of phenotypic divergence in a malignant glioma, and
      constitutes a difficult diagnostic challenge. This heterogeneity reflects the
      potential for a range of phenotypic expression in malignant gliomas that needs to
      be recognized. We suggest microdissection genotyping as a molecular technique to
      better characterize these tumors.

PMID- 15148504
TI  - Thermogenesis and weight loss in obese individuals: a primary association with
      organochlorine pollution.
AB  - The main objective of this study was to investigate the potential impact of body
      organochlorine (OC) pollution on the adaptive change in thermogenesis induced by
      body weight loss. Fat mass (FM), fat-free mass (FFM), and sleeping metabolic rate
      (SMR) were measured in obese individuals before and after a weight-reducing
      program. The measured values of SMR were then compared to those predicted from a
      reference equation established from FM and FFM in control subjects. Plasma OC,
      leptin, total tri-iodothyronine, and free thyroxine concentrations were also
      measured in obese subjects before and after weight loss. After weight loss, the
      measured decrease in SMR was greater than that predicted by changes in FM and
      FFM. Increased plasma OC concentration was the factor explaining the greatest
      proportion of the difference between predicted and measured SMR changes induced
      by body weight loss. OC pollution seems to be a new factor affecting the control
      of thermogenesis in some obese individuals experiencing body weight loss.

PMID- 15148505
TI  - Generalized abdominal visceral fat prediction models for black and white adults
      aged 17-65 y: the HERITAGE Family Study.
AB  - OBJECTIVE: To determine if the relationship between abdominal visceral fat (AVF)
      and measures of adiposity are different between Black and White subjects and to
      develop valid field prediction models that accurately identify those individuals
      with AVF levels associated with high risk for chronic disease. DESIGN: Cross
      sectional measurements obtained from 91 Black men, 137 Black women, 227 White
      men, and 237 White women subjects, ages 17-65 y, who were participants in the
      HERITAGE Family Study, both at baseline and following 20 weeks of endurance
      training. MEASUREMENTS: AVF, abdominal subcutaneous fat (ASF), abdominal total
      fat (ATF), and sagittal diameter (SagD) were measured by computed tomography
      (CT). Body density was determined by hydrostatic weighing and was used to
      estimate relative body fat. Arm, waist (WC), and hip circumferences and skinfold
      thickness measures were taken, and BMI was calculated from weight (kg) and height
      (m(2)). Since CT abdominal fat variables were skewed, a natural log
      transformation (Ln) was used to produce a normal distribution. The General Linear
      Model (GLM) procedure was used to test the relationship between AVF and two
      different groups of variables-CT and anthropometric. RESULTS: The AVF of White
      men and women was significantly higher than that of Black men and women,
      independent of BMI, WHR, WC, and age, and was greater for men than for women. The
      CT model showed that the combination of SagD, Ln (ASF), age, and race accounted
      for 84 and 75% of the variance in AVF in men and women, respectively. The
      anthropometric model provided two valid generalized field AVF prediction
      equations. The Field-I equation, which included BMI, WHR, age and race, had an
      r(2) of 0.78 and 0.73 for men and women, respectively. The Field-II equation,
      which included BMI (women only), WC, age, and race, had an r(2) of 0.78 and 0.72
      for men and women, respectively. The field model equations became less accurate
      as the estimated AVF increased. CONCLUSIONS: (1) At the same age and level of
      adiposity, Black men and women have less AVF than White men and women. These
      differences are greater in men than in women. (2) The field regression equations
      can be generalized to the diverse group of adults studied, both in an untrained
      and trained state. However, their accuracy decreases with increasing levels of
      AVF.

PMID- 15148506
TI  - Relationship between sympathetic reactivity and body weight loss in morbidly
      obese subjects.
AB  - OBJECTIVE: To investigate the possible role of peripheral sympathetic activity in
      gastric bypass-induced body weight loss. SUBJECTS AND METHODS: In 42 morbidly
      obese patients (sex: 36 f/6 m; BMI: 46.0+/-0.7 kg/m(2)) undergoing a gastric
      bypass, the skin vasoconstrictor reflex in answer to a deep inspiration was
      measured by laser Doppler fluximetry. The extent of vasoconstriction, measured at
      the second finger of the left hand, was expressed as percent reduction of the
      basal blood flux (% vasoconstriction). Insulin sensitivity was assessed before
      surgery in a subset of patients (n=11), by the method of euglycemic,
      hyperinsulinemic clamp. Body weight and composition were evaluated before, and 3,
      6 and 12 months after surgery. At the same time points, energy intake (kJ/day)
      was evaluated by means of both food record diary and alimentary anamnesis.
      RESULTS: The % vasoconstriction, which was significantly (P=0.01) greater in
      normoglycemic subjects than in diabetic ones, was also significantly (P=0.03)
      related to the extent of insulin sensitivity measured during the euglycemic
      clamp. The % vasoconstriction showed a significant (P>0.0001), positive
      correlation with weight reduction obtained between the 6th and 12th months
      following surgery; as a consequence, % vasoconstriction was significantly
      (P=0.0004) related to the overall body weight loss achieved during the year
      following the operation. These correlations remained significant in multiple
      regression analysis with adjustment for age, initial body weight, plasma glucose
      and insulin (P=0.0007 and 0.006, respectively). The % vasoconstriction was also
      significantly (P=0.0006), negatively related to energy intake measured 12 months
      after surgery. CONCLUSIONS: In conditions of stable body weight, the sympathetic
      nervous system (SNS) reactivity is influenced by the degree of insulin
      resistance. A high capacity to activate the SNS, measured before surgery, is
      associated with both a larger gastric bypass-induced weight loss and a lower
      energy intake, at the phase of weight stabilization.

PMID- 15148508
TI  - [Classification of vascular anomalies (tumours and malformations). Clinical
      characteristics and natural history].
AB  - Vascular anomalies are divided into tumours and malformations. Haemangiomas are
      the most frequent amongst the former. Not normally present at birth, except in a
      premonitory form, they grow for 10-12 months due to hyperplasia, to subsequently
      undergo a progressive involution for a period that might last from ten to twelve
      years. They have an incidence of up to 12% in newborns; they are more common
      amongst girls; and are divided into superficial, deep and compound. Congenital
      haemangiomas and those that do not undergo involution are considered to be rare
      entities. Vascular malformations, with a lower incidence than haemangiomas, are
      always present at birth, they grow by hypertrophy and never undergo involution.
      According to the classification of the ISSVA, vascular malformations are divided 
      depending on the vessel affected - into capillary or venular (port-wine stain),
      venous, lymphatic, arteriovenous and combined or complex. Each of these has
      certain defining clinical and haemodynamic peculiarities. Within the final group
      are included some with a low flow, such as the Klippel-Trenaunay syndrome (venous
      and lymphatic venular vascular malformation associated with the muscular-skeletal
      hypertrophy of an extremity), and others with a high flow, such as the Parkes
      Weber syndrome.

PMID- 15148507
TI  - Pre-obese and obese agouti mice are sensitive to the anorectic effects of peptide
      YY(3-36) but resistant to ghrelin.
AB  - OBJECTIVE: The role of the melanocortin system in the feeding effects of
      peripheral peptide YY(3-36) (PYY(3-36)) and ghrelin was investigated using the
      agouti (A(y)/a) mouse as a model of abnormal melanocortin signalling.
      Furthermore, we examined whether the ectopic expression of agouti protein in
      A(y)/a mice results in complete MC4-R inhibition, by studying the effects of
      peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) and leptin on food
      intake. DESIGN: Adult A(y)/a mice were studied in the pre-obese state (7-8 weeks)
      and obese state (14-15 weeks). Animals received PYY(3-36) (0.02 micromol/kg), NDP
      alpha-MSH (0.2 micromol/kg), leptin (2 micromol/kg) (all 24 h fasted state) and
      ghrelin (0.2 micromol/kg) (fed state) by intraperitoneal (i.p.) injection. Age
      matched A(y)/a controls received i.p. saline. A separate cohort of wild-type
      (WT), age-matched controls received the same peptide dose or saline. Food intake
      was measured at 1, 2, 4, 8 and 24 h post-injection and compared in all four
      groups. Plasma leptin-, ghrelin- and PYY-like immunoreactivity (IR) were measured
      using radioimmunoassay (RIA). RESULTS: At 2 h post-injection, PYY(3-36) reduced
      food intake in pre-obese and obese A(y)/a mice, whereas ghrelin had no effect.
      Plasma ghrelin levels were significantly reduced in pre-obese and obese A(y)/a
      mice compared to WT controls. Peripheral administration of NDP-alpha-MSH and
      leptin acutely suppressed feeding (0-2 h) in pre-obese and obese A(y)/a mice.
      CONCLUSIONS: Responsiveness of pre-obese and obese A(y)/a mice to PYY(3-36)
      suggests that the melanocortin system may not be essential for the anorectic
      effects of this peptide. Melanocortinergic antagonism by agouti protein in A(y)/a
      mice may be sufficient to block the effects of endogenous, but not exogenous
      PYY(3-36), alpha-MSH and leptin. The mechanism underlying ghrelin resistance in
      A(y)/a mice may result from antagonism of hypothalamic melanocortin receptors-4
      by agouti protein, supporting a role for the melanocortin system in mediating
      ghrelin's actions.

PMID- 15148509
TI  - [Pathology and pathogenesis of haemangiomas].
AB  - Haemangiomas are tumours of infancy that are characterised by an initial phase of
      proliferation followed by an involution that, in the majority of cases, results
      in complete regression. From the pathological point of view, this is a
      hyperplasic proliferation of endothelial cells, which in the phase of
      proliferation form highly cellular masses with scarce vascular lumina, invading
      the dermis and/or subcutaneous cellular tissue. Cellularity diminishes in the
      phase of involution, the vascular lumina increases and there is a total, or near
      total, replacement by residual fibroadipose tissue. Its pathology is not well
      known and two theories are at present postulated: on the one hand, an intrinsic
      defect of the precursor endothelial cells that, through somatic mutation in a
      gene regulating angiogenesis, develop a phenotype that induces clonal
      proliferation. On the other hand, it might arise from cells originating in the
      placenta that embolize in foetal tissue during pregnancy or delivery. The
      similarities in antigen expression between haemangioma cells and placenta tissue
      support this second hypothesis.

PMID- 15148510
TI  - [Vascular tumors as syndromic indicators].
AB  - Haemangiomas can be indicators or clue signs for serious syndromes. Although less
      well known than those related to vascular malformations, there are some syndromes
      of important diagnostic value that are associated with haemangomias. Early
      recognition of problematic haemangiomas, together with a prompt intervention, may
      help to minimise their future morbidity. Neonatal haemangiomas warrant a special
      follow-up, since their growth pattern might be unpredictable at such an early
      age. Several clinical presentations are relevant because of their risk of
      syndromic association: cervicofacial haemangiomas, especially the extensive ones,
      may be markers for severe dysmorphic conditions like the PHACE(S) syndrome. Those
      distributed in the beard area are occasionally associated with haemangiomas of
      the airway. Lumbosacral haemangiomas usually hide an underlying spinal dysraphism
      or anorectal and urogenital anomalies. Multiple cutaneous haemangiomas may be a
      sign of visceral haemangiomatosis, most often hepatic, which becomes complicated
      by cardiac insufficiency or thyroid disease. Finally, there are two vascular
      neoplasms of rapid and invasive growth - kaposiform haemangioendothelioma and
      angioblastoma or tufted angioma - which, unlike infantile haemangioma, are
      markers for the Kasabach-Merritt syndrome.

PMID- 15148511
TI  - [Vascular malformations as syndromic markers].
AB  - Vascular malformations are static lesions, generally present at the moment of
      birth, formed by displasic vessels that grow in proportion to the growth of the
      child. They show normal cell replacements that constitute genuine mistakes of
      morphogenesis. The absence of regression of these malformations implies that they
      remain throughout the lifetime. The terminology describing this type of lesions
      gave rise to confusion in the medical literature until the International Society
      for the Study of Vascular Anomalies adopted a classification based on the
      dominant vessel of the malformation in 1996. This classification distinguishes
      between simple and complex forms depending on whether they affect one or several
      types of vessel. Vascular malformations can show themselves as isolated lesions
      or can be associated with other lesions, constituting the guide sign or being the
      principal marker of some syndromic complexes. This paper describes the principal
      signs and symptoms of those syndromes in which a vascular malformation is the key
      that raises suspicion about the existence of other associated lesions.

PMID- 15148513
TI  - [Imaging studies in the diagnosis of haemangiomas and vascular malformations].
AB  - The diagnosis of haemangiomata and cutaneous vascular malformations is based on
      clinical history and physical exploration. Imaging studies might be necessary to
      clarify and confirm the diagnosis, and in order to analyse the extent of the
      lesions by permitting an evaluation of their non-visible component as well as the
      affection of neighbouring structures. Finally, they also play an important role
      when it comes to planning and directing treatment, whether surgical or
      endovascular. The imaging techniques employed for haemangiomas and vascular
      malformations include: plain films ultrasound (Doppler), computerised tomography
      (Angio-CT), magnetic resonance (Angio-MR) and the angiographic techniques
      (arteriography, phlebography).

PMID- 15148512
TI  - [Complications in the evolution of haemangiomas and vascular malformations].
AB  - The differentiation of haemangiomas and vascular malformations is histological,
      clinical and prognostic. Although the majority of haemangiomas evolve towards
      spontaneous resolution, as many as 10% of cases can develop complications with
      ulceration, pain and haemorrhaging. Besides, the localisation of haemangiomas in
      the head and neck, next to vital structures, can compromise their functions.
      Hence, compression of the airway might be a vital emergency. Periorbital
      haemangiomas can give rise to amblyopia due to sensory deprivation or due to a
      restrictive strabismus. Lumbosacral haemangiomas must be studied with Nuclear
      Magnetic Resonance because of their frequent association with alterations in the
      midline at the level of the spine, anus, genitals or kidneys. Amongst visceral
      haemangiomas, hepatic haemangiomas are the most serious due to their association
      with congestive cardiac insufficiency. The association of extensive facial
      haemangiomas with anomalies of the central nervous system, vascular, cardiac,
      ocular and sternal anomalies, is denominated PHACE syndrome and is frequently
      complicated by mental deficiency, convulsions or ictus. Vascular malformations of
      trigeminal localisation are associated in up to 15% of cases with glaucoma or
      choroidal or leptomeningeal haemangiomas (Sturge-Weber syndrome). Combined
      vascular malformations localised in the extremities can become complicated with
      thrombophlebitis, regional osteolysis and even distant thromboembolisms (Klippel
      Treneaunay Syndrome). On the other hand, there is a coagulopathy due to
      consumption (Kassabach-Merrit Syndrome) that can complicate some vascular tumours
      such as the Kaposiform haemangioendothelioma and the tufted angioma. Finally, the
      complications of the treatments employed are reviewed.

PMID- 15148514
TI  - [Medical treatment of haemangiomas].
AB  - There are two clearly differentiated attitudes in the treatment of haemangiomas:
      the expectant attitude and the therapeutic, medical or surgical attitude. The
      expectant attitude can be appropriate in cases of small haemangiomas, far from
      areas of possible functional damage, and with a slow rate of growth; however, it
      must be remembered that after reaching their maximum involution, about 25% of
      haemangiomas show a significant deformity. Treatment should be applied to those
      haemangiomas that obstruct the visual axis, the airway, the auditory channel,
      (with alteration of functions such as vision, breathing, swallowing and urinary
      or intestinal functions); to those of rapid growth that produce or might produce
      tissue destruction or significant disfiguration, ulcerated lesions, and lesions
      with a great cutaneous extension or visceral affection, which can lead to
      congestive cardiac insufficiency, or haematological alterations. The recommended
      treatment is systemic corticosteroids, with an initial dose of 2 to 3 mg/kg/day
      of prednisone or prednisolone, administered once a day in the morning. The most
      frequent result is that growth is arrested, while a reduction in size is observed
      in less than half the cases. Intralesional administration of corticosteroids at
      intervals of between 4 and 8 weeks is an effective treatment that manages to
      avoid the adverse effects of systemic corticosteroids. Because of its adverse
      neurological effects, interferon is only recommended for lesions with a vital or
      severe functional risk that do not respond to corticosteroids. Cytotoxic drugs
      are another treatment group: intralesional bleomycin, vincristine,
      cyclophosphamide and pingiangmycin. Finally, other forms midway between medical
      and surgical treatment, such as intermittent compression, radiotherapy,
      cryotherapy, sclerotherapy, or the implantation of intralesional metals, might
      have a role to play in some specific haemangiomas.

PMID- 15148515
TI  - [Surgical treatment of haemangiomas].
AB  - The therapeutic approach to haemangiomas has changed slightly in recent years,
      moving from a generally conservative attitude to a more aggressive one in some
      cases. Chronic unaesthetic alterations that might be caused by haemangiomas,
      psychosocial traumas that can be caused during childhood, together with a better
      understanding of the behaviour of this type of lesions and advances in safer and
      more efficient surgical techniques are the basic factors behind this change of
      attitude. The present paper concentrates on the surgical treatment of
      haemangiomas, explaining their indications according to the stage of evolution at
      which they are found, and the surgical techniques employed to resect the lesion
      with the least morbidity. Similarly, a detailed treatment is given to those
      lesions that, because of their specific facial anatomical localization, require a
      special surgical treatment.

PMID- 15148517
TI  - [Sclerosing treatment of vascular malformations].
AB  - Traditional sclerotherapy with liquid sclerosants has been used for many years in
      the treatment of venous, lymphatic and low flow vascular malformations; it is
      efficient only with those vascular malformations of reduced size as a pre or post
      operational complement. The use of liquid sclerosants has the limitations of
      their dilution and progressive inactivation in a great haematic volume, the
      irregular distribution of the sclerosant on the endothelium, the handling of the
      sclerosant once injected and its imperceptibility to the echo-Doppler. In their
      turn, both ethanol and sodium morrhuate - the most habitually employed
      sclerosants - produce important secondary effects. On the contrary, the use of
      sclerosants, specifically polidocanol in microfoam form, significantly improves
      the procedure, since the microfoam displaces the blood instead of mixing and
      diluting itself in it, thus facilitating an homogeneous distribution of the
      sclerosant over the endothelial surface. Finally, the echogenicity of the
      microbubbles, which makes them directly visible, together with their manageable
      consistency, means that it can be distributed more easily throughout the treated
      area. We comment on our experience with 50 patients with venous or low flow
      vascular malformations, treated with this new form of sclerosant. Similarly, the
      use of OK-432 (picibanil) - as the recommended sclerosant treatment in lymphatic
      vascular, especially macrocystic, malformations - is reviewed and its protocol
      given.

PMID- 15148516
TI  - [Laser and intense pulsed light in the treatment of infantile haemangiomas and
      vascular malformations].
AB  - The use of the indications of the laser in treating vascular malformations and
      infantile haemangiomas is based on the theory of selective photothermolysis, in
      which the oxyhaemoglobin is the target chromophore on which the light of the
      laser acts, thus avoiding damage to neighbouring tissues. The pulsed dye laser is
      the most employed and at present is the treatment of choice in capillary
      malformations (port-wine stains). A variable response is obtained, with a
      substantial clearing of the colour of the lesion after several sessions.
      Application at early ages seems to improve the results. Venous malformations,
      especially those localised in the mucosa, respond better to the Nd:YAG laser;
      lymphatic malformations to the CO2 laser. Arteriovenous malformations rarely
      respond. Use of the pulsed dye laser in the phase of proliferation of the
      haemangiomas is subject to controversy, except where there is ulceration. A rapid
      re-epithelialization is obtained in these cases following its use. In the
      involution phase, patients with residual vascular lesions can benefit from other
      lasers such as KTP or Nd:YAG. If they show an atrophic surface and scars these
      complications improve with the CO2 laser or Er:YAG. New treatment modalities are
      emerging, such as photodynamic therapy, whose efficacy and safety, both in the
      treatment of haemangiomas and vascular malformations, have yet to be confirmed.

PMID- 15148518
TI  - [Surgical treatment of vascular malformations].
AB  - In spite of the numerous advances made over the last two decades, the treatment
      of congenital vascular malformations continues to be one of the greatest enigmas
      facing modern medicine. There are no clear criteria concerning the indications to
      be followed, and even less concerning the most appropriate therapeutic procedures
      for each type of lesion. The results of a strictly surgical approach are
      discouraging and today it is accepted that congenital vascular malformations
      should be attended to and treated by multidisciplinary units, combining the
      efforts of all the specialists involved in its treatment. This paper reviews the
      general principles of surgical treatment of congenital vascular malformations,
      without losing sight of the fact that the traditional role of isolated surgery in
      the treatment of congenital vascular malformations has been replaced by a
      multidisciplinary approach to this type of lesions, making it possible to
      integrate embolization, sclerotherapy and surgery to improve the results. The
      combination of these techniques reduces the risk and complications that existed
      when they were applied in an isolated form. Thus, surgical treatment should not
      be considered as an independent tool of treatment but as a therapeutic weapon
      integrated in the ensemble of measures directed at improving the quality of life
      of the patient with a congenital vascular malformation.

PMID- 15148519
TI  - [Protocol for the treatment of haemangiomas and/or vascular malformations].
AB  - When facing any vascular lesion present in the first moments of life, it is
      necessary to determine whether one is dealing with a tumour or a vascular
      malformation, given the different evolution of both processes and, hence, the
      different treatments they require. Diagnosis is basically clinical, based on a
      correct anamnesis and a detailed physical exploration. The first thing is to
      establish whether the lesion was present at birth and has changed size
      significantly, which would lead one to think of a haemangioma or, on the
      contrary, whether it is congenital and of very slow growth, such as vascular
      malformations. Facing dubious lesions, it is recommendable to carry out a biopsy
      with immunohistochemistry for the GLUT-1 antibody, specific to haemangiomas.
      Amongst the image tests, the first choice is usually ecography-Doppler, which
      makes it possible to determine whether the lesion is of high or low flow and to
      distinguish whether one is dealing with a haemangioma or a vascular malformation.
      Depending on the type of lesion, its localisation and degree of affectation it
      might be necessary to carry out radiography, magnetic resonance, phlebography,
      angio-resonance, arteriography or lymphoscintigraphy to complete the study. In
      more particular cases, such as multiple haemangiomatosis, it is necessary to
      carry out an hepatic echography, blood concealed in faeces, gastroscopy and
      colonoscopy, as well a determination of thyroid hormones; and in venous or
      combined extensive malformations, a haemogram and coagulation tests. On the other
      hand, the possible repercussions on other organs make a multidisciplinary
      approach essential, with the participation of different specialists. Due to the
      wide spectrum covered by vascular anomalies, treatment must be individualised.

PMID- 15148520
TI  - Promoting of melanocyte adhesion and migration by Malytea Scurfpea fruit in
      vitro.
AB  - The aim of this study was to investigate the effect of Malytea Scurfpea Fruit
      (MSF) on melanocyte adhesion and migration. Human epidermal melanocytes were
      treated with MSF and examined for adhesion to bovine serum fibronectin-coated
      culture dishes. Control and treated cells were also examined for migration into
      micropore filters coated with the same protein. Compared with control, MSF
      treated melanocytes adhered to the dishes more easily and migrated into the
      filters in a dose-dependent manner. MSF at a dose of more than 200 micro g/ml did
      not increase melanocyte adhesion and migration accordingly. With the exception of
      MSF 10 micro g/ml, at every concentration of MSF there were significant
      differences between treated and untreated melanocytes (p < 0.01) when the
      adhesion test was studied. Regarding migration, even at a concentration of MSF 10
      micro g/ml, obviously increased cell numbers were found compared with MSF
      untreated melanocytes (p < 0.01). MSF promoted melanocyte adhesion and migration;
      this could explain, in part, the capacity of MSF to regulate melanocyte function
      in vitiligo.

PMID- 15148521
TI  - Occurrence of substance P(1-7) in the metabolism of substance P and its
      antinociceptive activity at the mouse spinal cord level.
AB  - Substance P (SP), which is known as a pain transmitter or modulator in the spinal
      cord, was degraded by the synaptic membranes of the mouse spinal cord. The major
      metabolites of SP were phenylalanine, SP(1-6), SP(1-7), SP(1-9), SP(8-9) and
      SP(10-11). Degradation of SP was inhibited by a metal chelator, o-phenanthroline,
      and also by specific inhibitors of endopeptidase-24.11, thiorphan and
      phosphoramidon. In contrast, captopril (a specific inhibitor of angiotensin
      converting enzyme), bestatin (a specific inhibitor of aminopeptidase) and Z-321
      (a specific inhibitor of prolylendopeptidase) showed little effect on the
      degradation of SP. The accumulation of the major cleavage products was strongly
      inhibited by phosphoramidon and thirophan, as well as the initial cleavage of SP.
      Thus, endopeptidase-24.11 plays a major role in SP degradation in the mouse
      spinal cord. Additional in vivo experiments were performed to investigate the
      antinociceptive effect of SP(1-7), a major product of SP that was detected after
      incubation with spinal synaptic membranes. In the mouse tail-flick test, the
      intrathecal administration of SP(1-7) (1.0-4.0 pmol) increased tail-flick latency
      in a dose-dependent manner. These results suggest that degradation of SP by
      spinal endopeptidase-24.11 may lead to the formation of SP(1-7), which has an
      ability to produce antinociceptive effects at the mouse spinal cord level.

PMID- 15148522
TI  - Receptor mechanisms involved in the anticonvulsant effect of melatonin in maximal
      electroshock seizures.
AB  - The present study investigates the mechanisms involved in the anticonvulsant
      effect of melatonin in maximum electroshock (MES) seizures. Melatonin (25-100
      mg/kg) dose-dependently decreased the duration of tonic hindlimb extension
      (THLE). The anticonvulsant effect of melatonin was blocked by bicuculline, a
      GABA(A) receptor antagonist, and luzindole, an ML(1) receptor antagonist, while
      prazosin, an ML(2) receptor antagonist, enhanced the anticonvulsant actions of
      melatonin in this seizure model. Administration of serotonergic agents, mianserin
      and ondansetron, along with melatonin, increased the antiseizurogenic activity of
      melatonin, while buspirone had no effect. Pretreating the animals with diazepam,
      carbamazepine or lamotrigine enhanced the anticonvulsant effect of melatonin.
      Melatonin thus appears to be an effective anticonvulsant, and melatonin ML(1)
      receptors, GABAergic and serotonergic mechanisms may play an important role in
      mediating the anticonvulsant activity of melatonin in electroshock seizures.

PMID- 15148523
TI  - Potentiation of the antiinflammatory effect of Anacardium occidentale (Linn.)
      stem-bark aqueous extract by grapefruit juice.
AB  - In an attempt to scientifically appraise some of the ethnomedical uses of
      Anacardium occidentale Linn. (family: Anacardiaceae), the present study was
      undertaken to examine the antiinflammatory effect of the plant's stem-bark
      aqueous extract in rats. Young adult male Wistar rats weighing 250-300 g were
      used. The antiinflammatory effect of A. occidentale stem-bark aqueous extract
      alone and in combination with grapefruit (Citrus paradisi Macf.) juice was
      investigated on fresh egg albumin-induced rat paw edema. Like diclofenac (100
      mg/kg p.o.), aqueous extract of A. occidentale stem-bark (800 mg/kg p.o.)
      produced time-related, sustained and significant reduction (p < 0.05-0.001) of
      the fresh egg albumin-induced acute inflammation of the rat hind paw. However,
      the antiinflammatory effect of the plant extract was found to be approximately 8
      15 times less than that of diclofenac. Coadministration of grapefruit juice (5
      ml/kg p.o.) with A. occidentale stem-bark aqueous extract (800 mg/kg p.o.) or
      diclofenac (100 mg/kg p.o.) significantly potentiated (p < 0.05-0.001) the
      antiinflammatory effects of the crude plant extract and diclofenac on fresh egg
      albumin-induced rat paw edema. Although A. occidentale stem-bark aqueous extract
      is less potent than diclofenac as an antiinflammatory agent, the results of this
      experimental animal study indicate that the plant extract possesses
      antiinflammatory activity, and thus lend pharmacological support to the folkloric
      use of the plant in the management and/or control of arthritis and other
      inflammatory conditions among the Yoruba-speaking people of western Nigeria.

PMID- 15148524
TI  - Effect of insulin hypoglycemic stress on nociceptive responses to mu- and kappa
      opioid receptor agonists at LH-surge in female rats.
AB  - In a randomized, prospective, controlled and crossover study, the effects of
      insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid
      receptor directed drugs during steroid-induced preovulatory LH-surge were seen in
      ovariectomized female rats. Ovariectomized rats were equally distributed in two
      groups of 10. In group 1 rats, LH-surge was induced by sequential treatment with
      estradiol benzoate 7.5 micro g/rat s.c. and progesterone 5 mg/rat s.c., whereas
      in group 2 rats, vehicles of estradiol benzoate and progesterone were given in a
      sequential manner. A third group consisted of sham-operated rats, which received
      no treatment. Rats were exposed to insulin-induced hypoglycemic stress 1 h before
      the peak of LH-surge. Antinociceptive responses of morphine, buprenorphine and
      pentazocine were observed at peak LH-surge during hypoglycemic stress. Increased
      nociceptive responses to noxious stimulus and decreased percent maximal possible
      effect for morphine, buprenorphine and pentazocine at LH-surge were significantly
      (p < 0.01) reversed during insulin hypoglycemic stress. There was a significant
      (p < 0.01) decrease in the ED(50) values of morphine, buprenorphine and
      pentazocine during hypoglycemic stress. The present study indicates that insulin
      hypoglycemic stress is responsible for increased antinociceptive activities of
      morphine, buprenorphine and pentazocine and decreased sensitivity to noxious
      stimulus in ovariectomized rats with or without steroid-induced LH-surge.

PMID- 15148525
TI  - Evidence that angiotensin II enhances apomorphine-induced jaw movements via AT1
      receptors in the ventrolateral striatum: studies by magnet-sensing system in
      freely moving rats.
AB  - The role of angiotensin AT(1) receptors in the ventrolateral striatum in
      modulating apomorphine-induced jaw movements was studied using a magnet-sensing
      system combined with an intracerebral drug microinjection technique in freely
      moving rats. Bilateral injections of angiotensin II (1 and 2 micro g/0.2 micro l
      in each side) into the ventrolateral striatum, which alone did not significantly
      elicit jaw movements, dose-dependently enhanced apomorphine (1 mg/kg i.v.)
      induced repetitive jaw movements. The enhancement of apomorphine-induced jaw
      movements by angiotensin II (2 micro g) was dose-dependently antagonized by the
      angiotensin AT(1) receptor antagonist losartan (15 and 30 mg/kg i.p.), given 3 h
      before, while losartan (30 mg/kg i.p.) alone did not significantly affect the
      apomorphine (1 mg/kg)-induced jaw movements. These results indicate that
      angiotensin II enhances apomorphine-induced jaw movements via stimulation of
      angiotensin AT(1) receptors located in the ventrolateral striatum.

PMID- 15148526
TI  - Predicting the clinical course of breast cancer patients undergoing trastuzumab
      based therapy: an outlook.
AB  - Her-2/neu overexpressing breast cancer is associated with reduced overall
      survival, sex steroid receptor negativity and increased resistance to
      antihormonal therapy, and thus represents a subgroup with poor prognosis. The
      anti Her-2/neu receptor antibody trastuzumab (Herceptin), however, specifically
      targets this protein and provides a valuable addition to classical systemic
      therapies. Unfortunately, not all tumors that express Her-2/neu protein are also
      adequate candidates for trastuzumab therapy. Therefore, most clinicians now
      consider Her-2/neu oncoprotein overexpression and/or her-2/neu gene amplification
      a prerequisite for trastuzumab-based antineoplastic therapy. Nevertheless, due to
      the relatively low response rates that are observed even in this preselected
      patient cohort, better response predictors are clearly needed. Here, we review
      established parameters such as Her-2/neu immunohistochemistry (IHC) and
      fluorescence in situ hybridization (FISH) and their ability to predict the
      clinical course of trastuzumab-treated breast cancer. We also evaluate promising
      parameters such as serum levels of the Her-2/neu extracellular domain (ECD) and
      the activation status of Her-2/neu oncoprotein (pHer-2/neu), and their use in the
      clinical setting. Finally, novel tumor-specific such as tumor M2-PK, IGF-IR and
      p53 are discussed and their potential to predict the efficacy of trastuzumab is
      assessed.

PMID- 15148527
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R),
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: ABI-007, adalimumab, adefovir
      dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine
      hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab,
      BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B,
      BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride,
      CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa,
      desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA
      paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated),
      duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569,
      elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium,
      eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir
      calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI
      2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate
      sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin,
      ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin
      gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab,
      ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed
      disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide
      acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid
      distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide,
      repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184,
      semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin;
      Tadalafil, tesmilifene hydrochloride, theratope, tipifarnib, tirapazamine,
      topixantrone hydrochloride, trabectedin, traxoprodil, Tri-Luma; Valdecoxib,
      valganciclovir hydrochloride, vinflunine; Ximelagatran; Ziconotide.

PMID- 15148528
TI  - The promise of thalidomide: evolving indications.
AB  - Thalidomide was first used in the late 1950s but it was withdrawn from the market
      in the 1960s for its notorious teratogenic effects. This drug was more recently
      rediscovered as a powerful immunomodulatory and antiinflammatory agent and was
      approved by the FDA in 1998 for treatment of erythema nodosum leprosum.
      Thalidomide has shown great promise in advanced or refractory multiple myeloma
      either alone or in combination with other agents. It has also demonstrated
      benefits in a wide variety of disparate conditions such as aphthous and genital
      ulcers, cancer cachexia, HIV, tuberculosis and chronic graft versus host disease.
      Thalidomide is being investigated for treatment of renal cell carcinoma, and
      liver and thyroid cancers. Better understanding of its many mechanisms of action
      has provoked great interest in its potential use for treatment of various
      disorders. This review focuses on thalidomide's mechanisms of action,
      biochemistry, pharmacokinetics and its use in erythema nodosum leprosum as well
      as multiple myeloma, graft versus host disease, and renal cell carcinoma.

PMID- 15148529
TI  - The role of botulinum toxin in neurourology.
AB  - Botulinum toxin is a presynaptic neuromuscular blocking agent that induces a
      selective and reversible muscle weakness of up to several months when injected
      intramuscularly in minute quantities. Different medical disciplines have applied
      the toxin to treat mainly muscular hypercontraction. For neurourologically
      impaired patients, the reported successful treatment of neurogenic detrusor
      overactivity and detrusor sphincter dyssynergia with botulinum-A toxin is a
      promising alternative option to conservative medication or surgery. This review
      of the literature presents current indications, techniques for and results of the
      use of botulinum toxin in neurourologically impaired patients and aims to give an
      insight into this new therapeutic option.

PMID- 15148530
TI  - An update on the use of 5alpha-reductase inhibitors.
AB  - Twelve years ago, finasteride, the first 5alpha-reductase inhibitor, was
      introduced as drug therapy for benign prostatic hyperplasia, and more recently
      dutasteride has emerged as an alternative. The efficacy, safety and ability of
      these 5alpha-reductase inhibitors to reverse the natural progression of benign
      prostatic hyperplasia have been convincingly demonstrated and both drugs are now
      well established in the medical armamentarium against the disease. Given the
      multifactorial etiology of benign hyperplasia, the usefulness of 5alpha-reductase
      inhibitors in combination with alpha adrenergic blockers has also been
      investigated and justified in select patients. Wider applications of 5alpha
      reductase inhibitors are also emerging, though their perhaps most important new
      role as chemopreventive agents remains unclear.

PMID- 15148531
TI  - Overview of treprostinil sodium for the treatment of pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension is a life-threatening disorder that refers to a
      group of diseases characterized by an abnormal elevation of the blood pressure
      within the pulmonary circulation due to a vasculopathy of the pulmonary
      microcirculation (1). If left untreated, the overall prognosis of pulmonary
      arterial hypertension is poor, with a 5-year survival rate of 34%. The most
      common cause of death is progressive right-sided heart failure (2). There is no
      pharmacologic cure for pulmonary arterial hypertension, and a team approach is
      required for the proper care of these patients (3). Treatment is directed at
      improving clinical symptoms, increasing exercise tolerance and extending
      survival. Until just a few years ago, standard treatment options for the
      treatment of pulmonary arterial hypertension were limited and included coumarin
      derivatives, calcium channel blockers, diuretics, digoxin and oxygen
      supplementation (4). In the last decade, the therapeutic options for pulmonary
      arterial hypertension have made considerable advances. In at least three major
      randomized controlled trials, the continuous intravenous infusion of
      epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability,
      has been shown to improve exercise tolerance, hemodynamics, survival and quality
      of life in patients with New York Heart Association (NYHA) functional classes III
      and IV with either primary pulmonary hypertension or pulmonary arterial
      hypertension associated with scleroderma (5-9). Epoprostenol has now become a
      mainstay therapy in the long-term treatment of primary pulmonary hypertension or
      pulmonary arterial hypertension associated with scleroderma. Nevertheless,
      epoprostenol is far from an ideal form of therapy. Issues such as the short half
      life of the drug, need for continuous central intravenous access and significant
      side effects have led to the development of more stable prostacyclin analogues as
      alternative therapies for primary pulmonary hypertension. These alternative
      therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous
      delivery). As a result, the Food and Drug Administration (FDA) recently approved
      treprostinil for the treatment of pulmonary arterial hypertension in patients
      with NYHA classes II-IV. This review will offer a discussion of the basic
      pharmacology of treprostinil, its similarities to and differences from
      epoprostenol, the animal studies as well as the initial investigational studies
      leading to its FDA approval, and clinical uses of the drug alone or in
      combination with newer therapies directed at pulmonary arterial hypertension
      developed over the last decade.

PMID- 15148532
TI  - The treatment of cancer pain.
AB  - Pain is probably one of the most common cancer symptoms. In addition to being a
      major source of suffering and disability, cancer pain is extremely frightening
      for patients and their families. This review discusses the current options for
      treating cancer pain, focusing on the pharmacological agents currently available
      and briefly exploring some of the surgical options for pain management. The
      authors propose to adjust the World Health Organization (WHO) pain management
      ladder from its current three-step approach to a more sophisticated five-step
      algorithm that includes physical and psychological modalities along the entire
      continuum of care and adds two more steps related to neuromodulative and
      neurodestructive procedures once the opioids fail.

PMID- 15148533
TI  - Use of pharmacogenetics to guide warfarin therapy.
AB  - The Human Genome Project heralds new opportunities for pharmacogenetics, the use
      of genetics to individualize the application of pharmaceuticals in the practice
      of medicine (1-3). Single nucleotide polymorphisms (SNPs) and other genetic
      variants in genes responsible for absorption, metabolism and excretion have been
      associated with alterations in drug disposition or effect. Warfarin is a
      potential target for pharmacogenetics-based dosing because of its wide use,
      variability in individual response, high prevalence of genetic variants and
      severity of adverse drug reactions (4). The genotype assays for genetic variants
      relevant to warfarin are widely used and are being developed for commercial use
      (5), making the promise of a pharmacogenetics-based approach a near reality.

PMID- 15148535
TI  - The emerging technologies of neural xenografting and stem cell transplantation
      for treating neurodegenerative disorders.

PMID- 15148534
TI  - Enfuvirtide.
AB  - Enfuvirtide (Fuzeon, T-20), jointly developed by Trimeris Inc. and Roche
      Pharmaceuticals, is the first of a new class of antiretroviral agents called
      fusion inhibitors that block HIV-1 entry into the host cell by binding to the
      gp41 subunit of the HIV-1 envelope glycoprotein. In vitro and in vivo studies
      have demonstrated potent antiretroviral activity among HIV-positive patients,
      including those with multi-drug resistant virus. The pharmacokinetic profile of
      subcutaneously administered enfuvirtide allows for twice-daily administration,
      although the possibility of once-daily dosing has not been excluded. Phase II and
      III clinical studies conducted to date have confirmed that enfuvirtide is an
      effective and safe drug for treating both adult and pediatric HIV-1-positive
      patients, with only mild or moderate adverse effects being reported.

PMID- 15148537
TI  - The South African Lipid Guidelines: is there a need for an update?

PMID- 15148536
TI  - Facets of the metabolic syndrome in Dahl hypertensive rats.
AB  - We recently established that the Dahl salt-sensitive rat, a model for genetic
      salt-sensitive hypertension, was insulin resistant. This study was undertaken to
      evaluate whether other features of the metabolic syndrome developed in this
      animal model. Two groups of 16 Dahl salt-sensitive (DSS) rats and their controls,
      Dahl salt-resistant (DSR) rats were used. For eight weeks, half of each group was
      fed a standard diet with low sodium content (85 mmol Na/kg diet) while the
      remainder was fed a high-sodium diet (340 mmol Na/kg diet). Weekly systolic and
      diastolic blood pressures were measured for all animals. At the end of eight
      weeks, the urinary Na(+)/K(+) ratio, fasting blood glucose, plasma uric acid and
      blood lipids were determined for all animals. The same parameters were measured
      in two additional matched weanling DSS and DSR groups of eight animals each.
      Adult DSS rats became hypertensive, with the DSS high-salt group exhibiting both
      genetic hypertension and the pressor effects of a high-salt diet. The DSS high
      salt and weanling groups exhibited a lowered urinary Na(+)/K(+) ratio, indicative
      of greater sodium retention, when compared to their respective DSR groups (p <
      0.05). No strain differences were observed in the uric acid levels. However a
      high-salt diet in both DSS and DSR groups elevated uric acid levels. Weanling and
      DSS high-salt groups showed increased total plasma cholesterol when compared to
      their corresponding DSR groups (p < 0.05). In addition, the DSS high-salt group
      also had both increased total plasma cholesterol and high-density lipoprotein
      (HDL) cholesterol when compared to the DSS low-salt group (p < 0.05). No
      significant differences in blood glucose and plasma insulin were observed in the
      adult groups. The weanling DSS group showed a marked hyperinsulinaemia,
      suggesting that DSS rats were possibly insulin resistant even before hypertension
      was fully established. This could indicate that insulin resistance and
      hypertension may be inherited as separate traits that develop in a parallel but
      independent manner.

PMID- 15148538
TI  - New developments in pharmacotherapy.

PMID- 15148539
TI  - Re: The ECG: what is normal?

PMID- 15148540
TI  - Supraventricular tachycardia in children.
AB  - The mechanisms causing different supraventricular tachycardias can be identified
      with the aid of the 12-lead ECG using Tipple's approach. The main aims of this
      retrospective study were to use the 12-lead ECG to determine the underlying
      mechanisms of supraventricular arrhythmias and to evaluate the effectiveness of
      the treatment modalities used. Forty-one patients were included in the study. The
      main findings were: nine of the 41 patients had atrial tachycardias while
      junctional tachycardia occurred in 32/41 of our patients. The underlying
      mechanisms causing the junctional tachycardias were: AVNRT (n = 21), AVRT (n =
      10) and JET (n = 1). Of the 10 patients presenting with AVRT, eight were less
      than one year old. AVNRT occurred more often in the older age group (>1 year of
      age). Fifteen of the 41 patients had spontaneous cessation of their
      supraventricular tachycardia. The drug most commonly used during the acute and
      long-term phases was digoxin. Amiodarone was used in six patients with an 80%
      success rate. In the early 80s verapamil was used in five patients with a 100%
      success rate. It is important to note that verapamil is no longer used in
      children due to its side effects. Lately, adenosine phosphate is the drug of
      choice in most supraventricular tachycardias. The management of supraventricular
      tachycardias in paediatric practice is mainly based on clinical studies and
      individual experience. Care must therefore be taken to choose medication regimens
      that are likely to be effective with the minimum risk of potentiating abnormal
      haemodynamics or conduction.

PMID- 15148541
TI  - High-dose atorvastatin therapy is required for significant improvement of
      endothelial function in heterozygous familial hypercholesterolaemic patients.
AB  - This study evaluated endothelial dysfunction (ED) by measuring flow-mediated
      vasodilation (FMD) and for six months documented changes in ED, LDL-C levels and
      serum concentrations of inflammatory markers with high- and low-dose atorvastatin
      therapy. In 23 heterozygous familial hypercholesterolaemic (FH) patients, FMD,
      LDL-C and inflammatory markers (sVCAM-1, sICAM-1, E-selectin and highly sensitive
      C-reactive protein) were measured at baseline (untreated) and on atorvastatin 20
      and 80 mg/day. In untreated patients, FMD was significantly reduced (mean +/- SD
      = 3.09 +/- 0.91%) compared with 10 normocholesterolaemic controls (8.71 +/-
      2.41%; p < 0.01). FMD improved non-significantly with atorvastatin 20 mg/day
      (5.60 +/- 1.17%), but showed a significant improvement (8.54 +/- 1.11%; p < 0.01)
      with atorvastatin 80 mg/day. LDL-C decreased markedly (-42.4%; p < 0.0001) on 20
      mg/day and decreased further (-48.6%; p < 0.05) on 80 mg/day. FMD improvement,
      however, did not correlate with LDL-C reduction. No significant changes occurred
      in any inflammatory markers. We concluded that ED was present in untreated FH
      patients and improved significantly on high-dose atorvastatin. There was no
      correlation between the changes in FMD and LDL-C, suggesting either a LDLC
      independent effect on ED, or that a marked reduction in LDL-C is required to
      normalise ED in FH.

PMID- 15148543
TI  - Transoesophageal atrial pacing stress echocardiography in coronary artery
      disease: role, principles and methodology.
AB  - This article reviews the physiology and methodology of transoesophageal atrial
      pacing stress echocardiography (TAPSE) and clarifies its place among the other
      stress modalities. TAPSE correlates well with myocardial perfusion stress
      scintigraphy and coronary angiography and is a simple and safe diagnostic option
      for patients with suspected or known CAD, including those with recent myocardial
      infarction. Furthermore, the results of TAPSE have prognostic significance in
      patients with uncomplicated MI. Although, it is a highly feasible and safe
      technique, the cardiologist should be directly involved in the procedure and the
      personnel must be well trained in a large number of tests, as for any other
      stress echocardiographic modalities.

PMID- 15148542
TI  - Effectiveness of single detachable COOK coils in closure of the patent ductus
      arteriosus.
AB  - OBJECTIVE: To assess the efficacy and safety of single detachable coils in the
      closure of PDAs. METHODS: Review of cases in which a single detachable coil was
      implanted. The diameter of the ampulla was used to select coil size. Diameters of
      the PDA, ampulla and residual shunts were measured. RESULTS: There were 36
      patients with a mean minimal ductal diameter of 2.2 +/- 0.6 mm. Immediately after
      implantation, 46% of the patients had residual shunts and after 24 hours, only
      28%. A final spontaneous closure rate of 94% was observed after 21 months. There
      was a significant (p < 0.01) difference when minimal PDA diameter of those who
      had complete closure within 24 hours (median: 2 mm, interquartile range: 1.7-2.3
      mm) was compared to those with a residual shunt (median: 2.5 mm, interquartile
      range: 2.3-3.2 mm). Negligible complications were experienced. CONCLUSIONS:
      Single Cook detachable coils are effective for PDA closure with a low
      complication rate if properly selected. There is a high rate of spontaneous
      closure of trivial residual shunts. In patients with a minimal ductal diameter >
      or = 2 mm and a residual shunt, more coils may be considered.

PMID- 15148544
TI  - Individualising heart failure patients to beta-blocker therapy.

PMID- 15148545
TI  - Eprosartan dual action offers clinical benefit for elderly and overweight
      hypertensives.

PMID- 15148548
TI  - CHARM shows improvement in NYHA functional class with candesartan.

PMID- 15148549
TI  - Perindopril protects diabetics with coronary disease from cardiovascular death
      and heart attacks.

PMID- 15148552
TI  - From INSIGHTs on new-onset diabetes to ACTION in hypertensives with CAD.

PMID- 15148554
TI  - Central osteosclerosis with trichothiodystrophy.
AB  - Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder
      associated with defects in nucleotide excision repair. We report a 7-year-old boy
      with TTD due to mutation in the XPD gene. The patient has classic features of
      this condition, including brittle, sulphur-deficient hair, ichthyosis, growth
      retardation and developmental delay. In addition, he has radiological evidence of
      progressive central osteosclerosis. Although similar radiological findings have
      previously been reported in a small number of patients, this association is not
      widely recognised. We review the radiological findings in this and other similar
      cases and discuss the natural history of these bony changes.

PMID- 15148555
TI  - Colour Doppler ultrasound predicts chemotherapy response, but not survival in
      paediatric osteosarcoma.
AB  - BACKGROUND: Histological response to chemotherapy is an important prognostic
      factor in osteosarcoma, influencing therapeutic considerations. It would be
      advantageous to be able to assess chemotherapy response, and predict survival,
      prior to tumour resection. Colour Doppler US (CDUS) is non-invasive, non
      demanding for the patient, and easy to plan. This makes the method especially
      suitable for children, who comprise the majority of patients. OBJECTIVE: To
      establish the value of CDUS for pre-operative prediction of chemotherapy response
      and survival, using widely available US equipment. MATERIALS AND METHODS: CDUS
      was performed in 21 consecutive patients before and after chemotherapy. Peak
      systolic velocity (PSV) in the soft-tissue component of the tumour and quotient
      of resistive index (QRI) of the feeding artery and contralateral control were
      calculated. A pathologist, unaware of CDUS results, assessed the response to
      chemotherapy after resection. RESULTS: QRI change after chemotherapy was
      significantly higher in histological responders. No correlation of QRI change
      with survival was found. There was no significant difference in PSV change
      comparing any subgroup. CDUS appeared useful in predicting chemotherapy response
      (sensitivity 83%, specificity 86%), especially for negative response (predictive
      value 92%). Survival could not be predicted accurately. CONCLUSIONS: CDUS can
      predict chemotherapy response, but not survival. The method could be useful in
      planning treatment prior to definitive surgery.

PMID- 15148556
TI  - No urine, no urinary clearance.

PMID- 15148557
TI  - NOS isoforms in adult human osteocytes: multiple pathways of NO regulation?
AB  - Until now, eNOS has been considered to be the predominant osteocytic nitric oxide
      synthase (NOS) isoform in bone. We previously studied the distribution of eNOS
      protein expression in the human femoral neck because of its possible involvement
      in the response to load. Studies in rat and human fracture callus have shown that
      nNOS mRNA is expressed sometime after fracture, but no study has yet
      immunolocalized NOS isoforms in mature adult human bone. In this study, we have
      examined the distribution of NOS isoforms in iliac osteocytes. Frozen sections
      (10 microm) were cut from transiliac biopsies from 8 female osteoporotic patients
      (range, 56-80 years) and from 7 female postmortem femoral neck biopsies (range,
      65-90 years). Sections were incubated overnight in antiserum for eNOS, nNOS, or
      iNOS followed by peroxidase/VIP substrate detection. We used eNOS and iNOS
      antisera directed against the C-terminus. For nNOS, three different antisera were
      used, two binding to different C-terminal epitopes and one binding to N-terminal
      epitope. Sections were then incubated in propidium iodide or methyl green to
      detect all osteocytes. eNOS antibody was able to detect eNOS epitopes in
      osteocytes. All three nNOS antibodies detected nNOS epitopes in osteocytes, but
      those directed against the C-terminus had higher detection rates. iNOS was rarely
      seen. In the iliac crest, the percentage of osteocytes positive for nNOS was
      higher than that for eNOS (cortical: nNOS 84.04%, eNOS 61.78%, P < 0.05;
      cancellous: nNOS 82.33%, eNOS 65.21%, P < 0.05). In the femoral neck, the
      percentage of osteocytes positive for nNOS (60.98%) was also higher than that for
      eNOS (40.41%), although this difference was not statistically significant. In
      conclusion, both eNOS and nNOS isoforms are present in osteocytes in the iliac
      crest and femoral neck.

PMID- 15148558
TI  - Risedronate and pamidronate treatment in the clinical management of patients with
      severe Paget's disease of bone and acquired resistance to bisphosphonates.
AB  - The aim of this study was to evaluate the efficacy and safety of risedronate and
      pamidronate in 30 patients (mean age = 57.86 +/- 8.90 years) with severe Paget's
      disease of bone (PDB), showing acquired resistance to intravenous (IV) clodronate
      treatment. Fifteen patients were treated with oral risedronate (30 mg/day for 8
      weeks). Treatment was repeated in patients without evidence of PDB remission
      [total alkaline phosphatase (tALP) serum levels in the normal range] at day 120.
      Fifteen patients were treated with IV pamidronate (30 mg/day for 3 days).
      Pamidronate treatment (60 mg/day for 3 days) was repeated in patients without
      evidence of PDB remission at day 120. At day 60, a significant decrease in tALP
      serum levels was obtained in all pagetic patients. At day 360, 13 (86.6%)
      patients treated with risedronate achieved PDB remission, 9 patients during the
      initial treatment and 4 after retreatment. Two patients showed a significant
      decrease in tALP serum levels without clinical remission after two risedronate
      treatments. At the same time, 12 (80%) patients treated with pamidronate achieved
      PDB remission, 6 patients during the first treatment and 6 after retreatment.
      Three patients showed a significant decrease in tALP serum levels but no clinical
      remission after two pamidronate courses. Two of these patients showed a relapse
      during the study. The incidence of minor side effects and transient
      hyperparathyroidism related to bisphosphonate treatment was significantly lower
      after risedronate therapy. In patients with resistant PDB, oral risedronate
      therapy has comparable efficacy to IV pamidronate with a lower incidence of
      treatment-related side effects.

PMID- 15148559
TI  - Osteoblast-like cells complete osteoclastic bone resorption and form new
      mineralized bone matrix in vitro.
AB  - Bone remodeling involves old bone resorption by osteoclasts and new bone
      formation by osteoblasts. However, the precise cellular mechanisms underlying
      these consecutive events remain obscure. To address this question in vitro, we
      have established a cell culture model in which the resorption lacunae are first
      created by osteoclasts and osteoblast-like cells accomplish the subsequent bone
      formation. We isolated osteoclasts from rat bone marrow and cultured them on
      bovine bone slices for 48 hours to create resorption lacunae. After removing
      osteoclasts, confluent differentiated primary osteoblast cultures were
      trypsinized and the cells were replaced on the resorbed bone slices for up to 14
      days. The cultures were then examined by confocal microscopy, field emission
      scanning electron microscopy (FESEM), and transmission electron microscopy (TEM).
      Our data suggest that after osteoclastic bone resorption, osteoblast-like cells,
      not macrophages, remove the remaining organic matrix in the lacuna. After
      cleaning the lacuna, osteoblast-like cells deposit new collagen fibrils at the
      bottom of the lacuna and calcify the newly formed matrix only, as visualized by
      labeled tetracycline accumulation merely in the lacuna during the osteoblast
      culture. Furthermore, an electron-dense layer rich in osteopontin separates the
      old and new matrices suggesting formation of the cement line. Since the
      morphology of the newly formed matrix is similar to the natural bone with respect
      to the cement line and osteoid formation as well as matrix mineralization, the
      present method provides for the first time a powerful in vitro method to study
      the cellular mechanisms leading to bone remodeling also in vivo.

PMID- 15148560
TI  - Ribavirin, but not interferon alpha-2b, is associated with impaired osteoblast
      proliferation and differentiation in vitro.
AB  - Hepatitis C treatment with interferon alpha-2b (IFN-alpha) and ribavirin has been
      related to decreased bone mineral density. The aim of this study was to
      investigate the in vitro effects of different concentrations of ribavirin and IFN
      alpha on osteoblast-like cells. Human osteoblast-like cells obtained by the
      outgrowth of cells from bone chips were exposed to ribavirin (0.1-10 microg/mL)
      or IFN-alpha (0.1-1000 UI/mL). At regular time-points, cultures were harvested
      for posterior analysis. Alkaline phosphatase (ALP) activity was determined on
      days 7 and 14, and cell growth was accessed by C3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) and cell count on days 1, 3, 5, and 7. Flow
      cytometry analysis was used for investigating cell death on days 1, 3, 5, and 7.
      IFN-alpha affected ALP expression only at the higher concentration (1000 UI/mL)
      after 7 days (P < 0.05). No effects were detected in cell growth. In ribavirin
      treated cultures, concentrations higher than 2.5 microg/mL were associated with a
      decrease in ALP activity within 7 and 14 days (P < 0.01 and P < 0.001,
      respectively). Furthermore, the reduction in cell growth was dose-dependent and
      was detected after the fifth day. This decrease can be explained by an increase
      in the number of dead cells and a decrease in cell proliferation. In conclusion,
      our experiments demonstrated that ribavirin reduced, in a time- and dose
      dependent manner, the number of metabolically active cells through a decrease in
      proliferation and an increase in cell death, and induced an impairment in
      osteoblast differentiation. These negative effects of ribavirin on osteblast-like
      cells might contribute to the bone loss reported in vivo.

PMID- 15148561
TI  - Are bone turnover markers capable of predicting callus consolidation during bone
      healing?
AB  - The aim of this study was to determine the ability of the following bone turnover
      markers to monitor the course of callus consolidation during bone healing:
      Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline
      phosphatase (sALP), and amino-terminal propeptide of type III procollagen
      (PIlINP). Since interfragmentary movements have been proven to possess the
      ability to document the progression of bone healing in experimental studies,
      correlations between bone turnover markers and interfragmentary movements in vivo
      were investigated. Therefore, two different types of osteosyntheses representing
      different mechanical situations at the fracture site were compared in an ovine
      osteotomy model. Blood samples were taken preoperatively and postoperatively in
      weekly intervals over a nine-week healing period. At the same intervals,
      interfragmentary movements were measured in all sheep. After nine weeks, animals
      were sacrificed and the tibiae were evaluated both mechanically and
      histologically. Wide interindividual ranges were observed for all bone turnover
      markers. The systemic PICP level did not increase with callus consolidation. The
      bone-healing model seemed to influence the systemic level of PIIINP and sALP but
      no general correlation between bone turnover markers and interfragmentary
      movements could be detected. No differences between the different types of
      osteosyntheses and thus the different mechanical situations were observed. All
      analyzed markers failed as general predictors for the course of callus
      consolidation during bone healing.

PMID- 15148562
TI  - Co-induction of growth-associated protein GAP-43 and neuronal nitric oxide
      synthase in the cochlear nucleus following cochleotomy.
AB  - In adult animals, cochlear lesioning leads to a reactive synaptogenesis with a
      reemergence of growth-associated protein, GAP-43, in the auditory brainstem
      nuclei. In addition, nitric oxide (NO) is also implicated in synaptogenesis.
      Three isoforms of nitric oxide synthase (NOS) responsible for generating NO have
      been identified and, in neurons, the predominant isoform is neuronal NOS (nNOS).
      Studies in visual or olfactory systems have found that the NOS expression often
      correlates with periods of axonal outgrowth and synapse formation; whether NO
      plays a similar role in the auditory brainstem needs to be examined. In the
      present study, a unilateral cochleotomy was performed in adult mice to examine
      the relationship between the reemergence of GAP-43 and the expression pattern of
      nNOS. Following surgery, GAP-43 re-emerged in the ipsilateral anterior ventral
      cochlear nucleus (AVCN) and the immunoreactivity reached a climax around
      postoperative day (POD) 8; the same expression pattern as that reported in the
      previous literature is the indicator of synaptogenesis. As for the nNOS
      immunoreactivity, a dramatic redistribution from a mostly cytoplasmal to a
      predominantly membranous localization in the ipsilateral AVCN was found
      especially at POD 4. A similar redistribution pattern in the ipsilateral AVCN for
      the N-methyl-D-aspartate (NMDA) receptor was also observed at POD 4,
      corresponding to the fact that the activation of nNOS is coupled to calcium
      influx via the NMDA-receptor. Furthermore, the expression of cyclic guanosine
      monophosphate (cGMP) is an indicator for activity of soluble guanylyl cyclase
      (sGC), the substrate of NO, which reveals the target area of NO. Therefore, cGMP
      immunoreactivity was also examined and an obvious increase of cytoplasmal cGMP
      expression was observed around POD 4. Accordingly, it is suggested that nNOS
      activity correlates closely with the reactive synaptogenesis following a
      cochleotomy. Further evidence is shown by the results of fluorescent double
      staining; nNOS-positive cells were surrounded by GAP-43 labeled regions that
      appeared to be presynaptic boutons, and the vast majority of nNOS-positive cells
      also expressed cGMP. The former result indicates that, after surgery, there
      should be new terminal endings projecting onto the nNOS-positive cells in the
      AVCN. Furthermore, the latter result suggests a possible role of an autocrine
      mediator for nNOS in the AVCN.

PMID- 15148563
TI  - Rapid molecular typing of Tuber melanosporum, T. brumale and T. indicum from tree
      seedlings and canned truffles.
AB  - We have developed new DNA extraction and purification procedures for
      investigation of mycorrhized seedlings and canned truffles. Use of these
      procedures on approximately 100 mg initial material enabled good sample
      representation. For mycorrhized seedlings, Taq polymerase inhibitors were
      discarded irrespective of tree species. In routine analysis we systematically
      used consensus primers ITS1/ITS4 to check the absence of Taq polymerase
      inhibitors and the presence of fungus DNA. Positive response with ITS validates
      other positive or negative PCR results. Absence of amplification with ITS
      prevents validation of other results. For canned truffles, DNA harvested from
      ascocarps sterilized for one and a half hours at 115 degrees C was amplified with
      specific primers. We have developed consensus primers, named R12/F12, to check
      for the presence of amplifiable fungus DNA and the absence of Taq polymerase
      inhibitors. Here also, positive response with consensus R12/F12 validates other
      positive or negative PCR results. We have developed one primer pair specific for
      T. brumale and another specific for T. melanosporum. We can then characterize
      these two taxa, which enables the use of "truffle or truffled" French
      designations. We can also characterize T. indicum, the Asiatic black truffle that
      might fraudulently be sold as T. melanosporum and T. brumale. These three
      specific primer pairs were used independently of DNA extraction from tree
      seedlings or canned truffles. Our process is specific, sensitive, convenient, and
      quick.

PMID- 15148565
TI  - The effects of enrofloxacin on decorin and glycosaminoglycans in avian tendon
      cell cultures.
AB  - Tendonitis and tendon rupture have been reported to occur during or following
      therapy with fluoroquinolone antibiotics. Though the pathogenesis is unknown,
      several studies suggest that fluoroquinolone antibiotics alter proteoglycan
      content in soft tissues, including tendons, and thereby alter collagen
      fibrillogenesis. To better understand the mechanism of action of
      fluoroquinolones, we studied the effects of enrofloxacin, a widely used
      fluoroquinolone in veterinary medicine, on avian tendon cell cultures established
      from gastrocnemius tendons from 18-day-old chicken embryos. We found that cell
      proliferation was progressively inhibited with increasing concentrations of
      enrofloxacin. This was accompanied by changes in morphology, extracellular matrix
      content and collagen fibril formation as detected by electron microscopy. We also
      observed a 35% decrease in the content of total monosaccharides in enrofloxacin
      treated cells. The ratio of individual monosaccharides was also altered in
      enrofloxacin-treated cells. Enrofloxacin also induced the synthesis of small
      amounts of keratan sulfate in tendon cells. Moreover we observed enrofloxacin
      induced changes in glycosylation of decorin, the most abundant tendon
      proteoglycan, resulting in the emergence of multiple lower molecular bands that
      were identifiable as decorin after chondroitinase ABC and N-glycanase treatment
      of extracts from enrofloxacin-treated cells. Medium conditioned by enrofloxacin
      treated cells contained less decorin than did medium conditioned by control
      cells. We hypothesize that enrofloxacin induces either changes in the number of N
      linked oligosaccharides attached to the core protein of decorin or changes in
      decorin degradation process. In conclusion, our data suggest that enrofloxacin
      affects cell proliferation and extracellular matrix through changes in
      glycosylation.

PMID- 15148564
TI  - Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence.
AB  - RATIONALE: Alcohol dependence is characterized by the development of tolerance,
      withdrawal symptoms, and craving for alcohol. Chronic alcohol consumption causes
      neuroadaptive changes in the central dopaminergic and serotonergic system, which
      are partially reversible after detoxification. The severity and time-course of
      recovery of these neuroadaptive changes may depend on the genetic constitution of
      monoamine transporters and receptors and contribute to the relapse risk of
      alcoholics. OBJECTIVES: To assess the interaction between the genetic
      constitution and the in vivo availability of dopamine and serotonin transporters
      and receptors, chronic alcohol intake, alcohol craving and withdrawal. METHODS:
      Review of brain imaging studies that assess the genotype and availability of
      dopamine and serotonin transporters in detoxified alcoholics and healthy control
      subjects. RESULTS: Chronic alcohol intake induced neuroadaptive reductions in
      striatal dopamine transporter (DAT) availability, which were reversible during
      early abstinence. A polymorphism of the DAT gene (SLC6A3) was associated with the
      in vivo transporter availability and with the severity of alcohol withdrawal.
      Neurotoxic reductions in 5-HTT protein expression were limited to homozygous
      carriers of the long allele in the 5-HTT gene (SCL6A4) regulatory region and
      correlated with negative mood states. CONCLUSION: Genetic constitution interacts
      with the in vivo availability of central dopamine and serotonin transporters
      during alcohol detoxification and may affect the severity of alcohol withdrawal
      and clinical depression.

PMID- 15148566
TI  - Utilization of creatinine as an alternative nitrogen source in Corynebacterium
      glutamicum.
AB  - In order to utilize different nitrogen sources and to survive situations of
      nitrogen limitation, microorganisms have developed several mechanisms to adapt
      their metabolism to changes in the nitrogen supply. In this communication, the
      use of creatinine as an alternative nitrogen source in Corynebacterium
      glutamicum, the identification of a membrane protein involved in creatinine
      uptake, the transcriptional regulation of the corresponding gene, and expression
      regulation of the gene encoding the creatinine deaminase are reported. As shown
      by mutant analyses, RNA hybridization experiments and real-time PCR, the
      expression of two genes, crnT and codA, is increased in response to nitrogen
      limitation, and regulation depends on the global nitrogen regulator AmtR. In
      addition, synthesis of creatinine deaminase during nitrogen starvation was shown
      by two-dimensional gel electrophoresis and MALDI-TOF-MS followed by peptide mass
      fingerprint analysis.

PMID- 15148567
TI  - Coagulation in sepsis.
AB  - Coagulation abnormalities, ranging from a simple fall in platelet count to full
      blown disseminated intravascular coagulation, are a common occurrence in
      critically ill patients and have been associated with increased mortality. In
      sepsis, activation of the extrinsic coagulation pathway by tissue factor induces
      increased coagulation, and simultaneous depression of the inhibitory mechanisms
      of coagulation, and suppression of the fibrinolytic system results in a
      procoagulant state that may lead to the formation of microvascular thrombi
      disturbing organ microcirculation and promoting the development of organ
      dysfunction. Many inflammatory mediators are involved in the activation of
      coagulation, but many coagulation proteins are themselves actively involved in
      the inflammatory process. In this article, we explore the complex relationship
      between inflammation and coagulation and how improved understanding of this
      interaction has led to the development of new therapeutic agents for patients
      with severe sepsis.

PMID- 15148568
TI  - Practices in non-neutropenic ICU patients with Candida-positive airway specimens.
AB  - OBJECTIVE: To examine practices of French intensivists regarding the management
      of mechanically ventilated patients with Candida-positive airway specimens but no
      major risk factors for immunodepression. Design : Closed-item questionnaire with
      a clinical vignette. SETTING: 564 French intensive care units (ICUs).
      PARTICIPANTS: 198 intensivists who have a special interest in infectious diseases
      and who answered the questionnaire (response rate, 35.1%). INTERVENTION: None.
      MEASUREMENTS AND RESULTS: The respondents recommended bronchoalveolar lavage
      (62.6% of respondents), protected distal sampling and protected specimen brush
      (59.1%), transbronchial biopsy (38.9%), and tracheal aspiration (12.1%) for the
      diagnosis of candidal pneumonia. A positive airway specimen was felt by most
      respondents (83.3%) to indicate colonisation; 66.7% of respondents recommended
      tests for systemic candidiasis in this situation, and 56.5% serial sampling to
      compute the colonisation index. Azole derivatives were the preferred antifungal
      medications. The clinical vignette described a patient with chronic obstructive
      lung disease who required mechanical ventilation for an acute exacerbation and
      who had a tracheal aspirate positive for Candida. Responses varied widely, with
      37.8% of respondents diagnosing clinically insignificant colonisation but 24.2%
      recommending antifungal treatment and 61.6% serial testing to assess the Candida
      colonisation index. Intensivists with greater experience with severely
      immunocompromised patients were more aggressive in their diagnostic management.
      CONCLUSIONS: Wide variations occur among practices of French intensivists
      regarding Candida-positive airway specimens in patients without major risk
      factors for immunodepression. Additional studies are needed to improve our
      understanding of the links between Candida colonisation and infection and to
      determine the indications for pre-emptive antifungal treatment in non-neutropenic
      critically ill patients.

PMID- 15148569
TI  - Differential reversal of drug-induced small bowel paralysis by cerulein and
      neostigmine.
AB  - OBJECTIVE: Cerulein and neostigmine are prokinetic drugs whose potency and
      effective dose range are barely known. The aim of this study was to assess their
      benefit for normal and compromised peristalsis. DESIGN: In vitro, isolated
      segments of guinea pig small intestine. Setting : University laboratory.
      INTERVENTIONS: Small bowel segments were mounted in tissue baths and luminally
      perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine;
      inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the
      tissue bath. MEASUREMENTS AND RESULTS: Peristalsis was quantified via changes in
      the peristaltic pressure threshold. One-way and two-way analysis of variance
      (ANOVA) were used for statistical analysis. Cerulein (0.03-100 nM) stimulated
      normal peristalsis in a concentration-dependent manner and reversed paralysis of
      peristalsis induced by all inhibitory test drugs to a similar extent. The
      properistaltic effect of neostigmine was limited to a narrow concentration range
      (0.03-0.1 micro M), whereas concentrations >0.3 micro M inhibited peristalsis.
      Neostigmine more effectively counteracted blockage of peristalsis caused by
      atropine than that caused by hexamethonium. The inhibitory effects of epinephrine
      and sufentanil on peristalsis were reversed only at the concentration range of
      0.1-0.3 micro M neostigmine. CONCLUSIONS: Cerulein stimulates normal peristalsis
      in vitro at a wide concentration range and reverses blockage of peristalsis
      caused by drugs with a site of action either on the enteric nervous system or
      intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is
      limited to a small concentration range and best seen when peristalsis is
      depressed by blockage of cholinergic muscle activation.

PMID- 15148570
TI  - Hyperglycaemia and mortality in critically ill patients. A prospective study.
AB  - OBJECTIVE: To describe hyperglycaemia as a possible marker of morbidity and
      mortality in critically ill medical and surgical patients admitted to a
      multidisciplinary ICU. DESIGN: Prospective cohort study. SETTING: A 13-bed non
      cardiac multidisciplinary ICU in a university hospital. PATIENTS AND
      PARTICIPANTS: Adult patients consecutively admitted to the ICU in a 6-month
      period. Patients with fewer than 2 days' stay in the ICU and patients with known
      diabetes were excluded. MEASUREMENTS AND RESULTS: At admission a registration
      form was filled in including demographic data, first and second day APACHE II
      scores, infections and daily maximum blood glucose level. In surgical patients,
      high maximum blood glucose level during the stay in ICU was correlated with
      increased mortality, morbidity and frequency of infection. In medical patients,
      we found a non-significant trend towards a correlation between hyperglycaemia and
      morbidity and mortality, respectively. CONCLUSIONS: High blood glucose level
      during the stay in ICU was a marker of increased morbidity and mortality in
      critically ill surgical patients. In medical patients the same trend was found,
      but non-significant. The population of patients in the present study are
      heterogeneous and the results from surgical critically ill patients should not be
      generalised to medical patients.

PMID- 15148571
TI  - Isolation, characterization, and development of WRKY genes as useful genetic
      markers in Theobroma cacao.
AB  - There is currently an international effort in improving disease resistance and
      crop yield in Theobroma cacao L., an economically important crop of the tropics,
      using marker-assisted selection for breeding. We are developing molecular genetic
      markers focusing upon gene families involved with disease resistance. One such
      family is the WRKY proteins, which are plant-specific transcriptional factors
      associated with regulating defense responses to both abiotic and biotic stresses.
      Degenerate PCR primers were designed to the highly conserved DNA-binding domain
      and other conserved motifs of group I and group II, subgroups a-c, WRKY genes.
      Sixteen individual WRKY fragments were isolated from a mixture of T. cacao DNA
      using one pair of primers. Of the 16 WRKY loci investigated, seven contained
      single nucleotide polymorphisms within the intron as detected by sequence
      comparison of the PCR products. Four of these were successfully converted into
      molecular markers and mapped in an F2 population by capillary electrophoresis
      single strand conformation polymorphism analysis. This is the first report of a
      pair of degenerate primers amplifying WRKY loci directly from genomic DNA and
      demonstrates a simple method for developing useful genetic markers from members
      of a large gene family.

PMID- 15148573
TI  - Tumor-induced dysfunction in T lymphocytes: increased sensitivity to apoptosis.

PMID- 15148572
TI  - [Significance of neoadjuvant therapy before radical prostatectomy].
AB  - Neoadjuvant therapy before radical prostatectomy should increase survival in
      patients. This is necessary especially in patients with adverse prognostic
      factors for locally advanced disease, because in this stage radical prostatectomy
      as the only treatment results in a significantly reduced rate of progression-free
      survival. The aim of neoadjuvant therapy protocols is to increase local tumor
      control because of possible downstaging effects of the tumor and to improve
      systemic control because of elimination of circulating tumor cells and possible
      micrometastases. This review discusses the present and future aspects of
      neoadjuvant therapies in detail. The neoadjuvant hormonal therapy prior to
      radical prostatectomy results in a significant downstaging that does not
      translate into prolonged disease-free survival. This observation was made for
      short-term (3 months) and long-term (8 months) hormonal therapy. Therefore,
      neoadjuvant hormonal therapy has only a cosmetic effect on the pathological
      results and should not be advocated any more. Newer protocols have shown that
      neoadjuvant chemotherapy or hormone chemotherapy is feasible. The results
      obtained in non-randomized trials with small numbers of patients do not allow
      analyzing the efficacy of these protocols. Theoretically, neoadjuvant
      chemotherapy, especially a taxane-based protocol, which has shown efficacy in
      hormone-refractory disease, could improve disease outcome. Clinical trials are
      underway to prove this hypothesis. In the future, new therapeutic strategies
      could also be used in the neoadjuvant setting. It can only be speculated if
      antibody protocols or gene therapy will be used in this respect. In conclusion,
      there is no standard neoadjuvant protocol prior to radical prostatectomy. Whether
      chemotherapy will set a new standard for care has to be elucidated by the ongoing
      clinical trials.

PMID- 15148574
TI  - Predicting survival of patients with metastatic renal cell carcinoma.
AB  - The relationship between pretreatment clinical features and survival was studied
      from patients treated on clinical trials for metastatic renal cell carcinoma
      (RCC) at the Memorial Sloan-Kettering Cancer Center. The primary analysis was
      performed on 670 patients treated with cytokines or chemotherapy, from which a
      multivariate model was derived to predict survival. Studies which followed
      addressed: (1) the survival of patients given interferon-alpha as first-line
      therapy; (2) a comparison of survival for patients treated with chemotherapy
      versus cytokine therapy; and (3) survival of patients with non-clear cell
      histology. Prospective identification of patients more likely to benefit from
      cytokine therapy is important as a stratification factor in phase III trials, and
      in risk-directed therapy.

PMID- 15148575
TI  - HLA class II haplotypes predict favorable outcomes for patients with metastatic
      RCC.

PMID- 15148576
TI  - Interferon update.

PMID- 15148577
TI  - Immunotherapy in non-renal carcinomas.
AB  - Two discoveries have been crucial for the development of modern immunotherapy to
      human neoplasia. The first is the technology to produce recombinant proteins in
      large quantities, pioneered in the late 1970s, that has introduced recombinant
      cytokines as well as chimeric and humanized antibodies into the clinic. The
      second is the recognition of short peptides derived from intracellular proteins,
      which are carried to the cell surface on HLA molecules and present to T
      lymphocytes a sample of the intracellular protein pool for inspection, which
      provides the foundation for modern tumor vaccines. In this short review, the
      principles of and the results with cytokine treatment and vaccines in human
      neoplasms other than renal cancer are summarized.

PMID- 15148578
TI  - Protein kinase inhibitors: novel tools in cancer therapy.

PMID- 15148579
TI  - [Secondary remnant ureterectomy after incomplete diagnosis of a ureteral tumor].

PMID- 15148581
TI  - Hepcidin comes to the rescue.

PMID- 15148580
TI  - A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of
      its homologous coding gene.
AB  - We have earlier generated a mutant mouse in a course of making a transgenic line
      that exhibited interesting heterozygote phenotypes, which exhibited failure to
      thrive, severe bone deformities, and polycystic kidneys. This mutant mouse
      provided a clue to uncover a unique role of expressed pseudogenes. In this mutant
      the transgene was integrated into the vicinity of the expressing pseudogene of
      Makorin1 called Makorin1-p1. This insertion reduced transcription of the Makorin1
      p1, resulting in destabilization of the Makorin1 mRNA in trans via a cis-acting
      RNA decay element within the 5' region of Makorin1 that is homologous between
      Makorin1 and Makorin1-p1. These findings demonstrate a novel and specific
      regulatory role of an expressed pseudogene as well as functional significance for
      noncoding RNAs. Next, we developed an original algorithm to determine how many
      pseudogenes are expressed. Based on our examination 2-3% of human processed
      pseudogenes are expressed using the most strict criteria. Interestingly, the
      mouse has a much smaller proportion of expressed pseudogenes (0.5-1%).
      Pseudogenes are functionally less constrained, and have accumulated more
      mutations than translated genes. If they have some functions in gene regulation,
      this property would allow more rapid functional diversification than protein
      coding genes. In addition, some genetic phenomena that exhibit incomplete
      penetrance might be attributed to "mutation" or "variation" of pseudogenes.

PMID- 15148582
TI  - [Cardiogenic shock due to acute mitral dysfunction after deep venous thrombosis].
AB  - Open surgical embolectomy may be life-saving in massive pulmonary embolism. Up to
      now there are no studies concerning the question whether the foramen ovale should
      be examined routinely during surgery and whether an open foramen ovale should be
      closed routinely in the same session. Even case reports regarding this question
      are missing. We report on a 74-year old female patient who developed pulmonary
      embolism due to deep venous thrombosis. Six days after successful surgical
      embolectomy the patient developed cardiogenic shock due to a huge thrombus from
      the right atrium through the foramen ovale into the left atrium and the left
      ventricle. Immediate surgical embolectomy of a 40-50 cm huge thrombus was
      successful. Immediately after surgery upon the cardiac mass the patient showed
      symptoms of acute right leg ischemia. Thus a second embolectomy was necessary,
      the surgeon removed a 10 cm thrombus from the right external iliacal artery.
      There was no evidence of another pulmonary embolism timely related to the
      paradoxical embolism.

PMID- 15148583
TI  - [Palliative treatment for colorectal cancer].
AB  - Over 50,000 new cases of colorectal cancer are diagnosed in Germany every year.
      About half of these patients will be cured by surgery. The other reoccur or
      present primarily with advanced disease. Recently, the survival of patients with
      metastasized disease has been prolonged from about 6 months with best supportive
      care alone to more than 20 months with combination chemotherapy. Therefore,
      adequate palliation is reasonable. Irresectable liver metastasis can be treated
      by locally ablative procedures such as radiofrequency ablation (RFA) or
      laserinduced thermotherapy (LITT). In the individual case resection of lung or
      brain metastasis should be discussed. Practitioners have to deal with plenty of
      supportive opportunities e.g. analgesics, bisphosphonates, central acting drugs,
      nutrition but also with drug side effects. In centers different endoscopic or
      interventional radiologic procedures are offered. Considering the variety of
      therapeutic options, it is prudent to discuss individual treatment plans in an
      interdisciplinary "tumor board" and involve the practitioners in the decision
      making.

PMID- 15148584
TI  - [Secondary prevention of cardiovascular diseases].
AB  - Secondary prevention includes all measures to lower the risk of a relapse of a
      specific disease. For secondary prevention of cardiovascular diseases general
      measures and specific drug therapy are employed, according to the individual risk
      pattern. Among the general measures cessation of smoking is most important. In
      addition, an increase in daily exercise, a normalization of body weight and a
      healthy diet all lower the cardiovascular risk. For most cases secondary
      prevention includes also specific drug therapies. Aspirin, statins and beta
      blockers are the cornerstones of this drug therapy. After myocardial infarction
      most patients will also benefit from an ACE-inhibitor therapy.

PMID- 15148585
TI  - [Designer-drugs in tumor treatment].
AB  - Targeted approaches to treat malignant diseases in hematology and oncology based
      on the molecular basis of the disease represent a major breakthrough in modern
      medicine. Knowledge acquired in basic sciences such as functional understanding
      of products generated by chromosomal translocations, definition of surface
      molecules or molecular requirements of tumor-cell survival allow to specifically
      aim at the cause of or at a requirement for malignancy. This is in sharp contrast
      to conventional chemotherapy which mainly influences the ubiquitous pathways of
      nucleic acid metabolism and cell division. In addition to superior efficacy of
      these approaches one should-on the long run-expect a superior profile of side
      effects compared to standard regimens. These "designer-approaches" are mainly
      based on small molecules or monoclonal antibodies. Out of the broad spectrum of
      current concepts we would like to summarize some of the strategies that have
      already found their way from bench to bedside.

PMID- 15148587
TI  - The de novo chromosome 16 translocations of two patients with abnormal phenotypes
      (mental retardation and epilepsy) disrupt the A2BP1 gene.
AB  - The 16p13.3 breakpoints of two de novo translocations of chromosome 16, t(1;16)
      and t(14;16), were shown by initial mapping studies to have physically adjacent
      breakpoints. The translocations were ascertained in patients with abnormal
      phenotypes characterized by predominant epilepsy in one patient and mental
      retardation in the other. Distamycin/DAPI banding showed that the chromosome 1
      breakpoint of the t(1;16) was in the pericentric heterochromatin therefore
      restricting potential gene disruption to the 16p13.3 breakpoint. The breakpoints
      of the two translocations were localized to a region of 3.5 and 115 kb
      respectively and were approximately 900 kb apart. The mapping was confirmed by
      fluorescence in situ hybridization (FISH) of clones that spanned the breakpoints
      to metaphase spreads derived from the patients. The mapping data showed both
      translocations disrupted the ataxin-2-binding protein 1 ( A2BP1) gene that
      encompasses a large genomic region of 1.7 Mb. A2BP1 encodes a protein that is
      known to interact with the spinocerebellar ataxia type 2 ( SCA2) protein. It is
      proposed that disruption of the A2BP1 gene is a cause of the abnormal phenotype
      of the two patients. Ninety-six patients with sporadic epilepsy and 96 female
      patients with mental retardation were screened by SSCP for potential mutations of
      A2BP1. No mutations were found, suggesting that disruption of the A2BP1 gene is
      not a common cause of sporadic epilepsy or mental retardation.

PMID- 15148586
TI  - [MRSA-infections-treatment with intraoperatively produced gentamycin-vancomycin
      PMMA beads].
AB  - INTRODUCTION: We present gentamicin-vancomycin-impregnated beads that can be
      produced intraoperatively in moulds and demonstrated their successful use in ten
      cases of problematic Methicillin-resistant Staphylococcus aureus (MRSA)
      infection. METHODS: To produce the antibiotically loaded PMMA beads, a two-part
      mould of polyoxymethylene was used. The mixture of PMMA and antibiotic is poured
      into the mould halves, and during polymerisation the halves bond together. The in
      vivo antibiotic concentrations of wound secretion from the redon drainage were
      measured by fluorescence-polarisation immunoassay, and a concentration/time
      function was determined. The PMMA beads (2 g of vancomycin plus 0.5 g of
      gentamicin plus 40 g of PMMA) were implanted in ten patients aged 41-76 years.
      RESULTS: In all ten patients, the infection was cured (follow-up 15 months).
      CONCLUSION: The combination of gentamicin and vancomycin in the PMMA of
      standardised beads represents a good alternative in the treatment of MRSA
      infections. Understanding of the mechanism of antibiotic release from PMMA allows
      differentiated dosing during systemic application.

PMID- 15148588
TI  - D919G polymorphism of methionine synthase gene is associated with blood pressure
      response to benazepril in Chinese hypertensive patients.
AB  - Individual variation in drug response is considered to have multiple origins
      arising from interactions among susceptible genes and environmental factors. A
      total of 726 hypertensive patients who took benazepril 10 mg once a day for 15
      days and their families from Huoqiu county of Anhui Province, China, were used to
      study the association between D919G polymorphism of methionine synthase (MTR)
      gene and the antihypertensive effect of this angiotensin-converting enzyme
      inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and
      family-based association tests (additive model P=0.018, dominant model P=0.025)
      demonstrated that the 919G allele was associated with a significantly less
      diastolic blood pressure reduction. No significant association was found between
      the extent of systolic blood pressure reduction and benazepril therapy. Our
      finding suggests that the D919G polymorphism of the MTR gene may be a useful
      genetic marker to predict the antihypertensive effect of short-term benazepril
      therapy in hypertensive patients of Anhui Province, China.

PMID- 15148589
TI  - Polymorphisms of the prion protein gene (PRNP) in a Korean population.
AB  - Human prion protein gene (PRNP) has been considered to be involved in the
      susceptibility of humans to prion diseases. Polymorphisms of methionine
      (Met)/valine (Val) at codon 129 and of glutamic acid (Glu)/lysine (Lys) at codon
      219 are thought to play an important role in susceptibility to sporadic,
      iatrogenic and variant Creutzfeldt-Jakob disease (CJD). Although the genotype
      distribution of polymorphisms in PRNP open reading frame (ORF) has been reported
      in many European populations, among Asian groups, it has been reported only in
      the Japanese population. We examined the PRNP polymorphisms in 529 healthy
      Koreans. We observed that genotype frequencies at codon 129 was 94.33% Met/Met,
      5.48% Met/Val, and 0.19% Val/Val with an allele frequency of 0.971:0.029 Met:Val,
      and that genotype frequencies at codon 219 was 92.06% Glu/Glu, 7.94% Glu/Lys, and
      0% Lys/Lys with an allele frequency of 0.96:0.04 Glu:Lys. The frequencies of the
      Glu/Glu genotype ( chi(2)=10.075, P=0.0015) and of the Glu allele ( chi(2)=9.486,
      P=0.0021) at codon 219 were significantly higher in the Korean population than
      the Japanese population. In addition, the genotype frequency of heterozygotes
      (12.7%) at codons 129 or/and 219 was significantly lower in Koreans than in
      people from Great Britain ( chi(2)=89.52, P<0.0001). The deletion rate of one
      octarepeat (R2 deletion) was 0.38%, with 99.62% undeleted homozygotes and 0%
      deleted homozygote. To our knowledge, the R2 octarepeat deletion has never been
      found in people from countries other than Korea. The data of PRNP polymorphism at
      codon 219 suggest that Koreans may be more sensitive to sporadic CJD than the
      Japanese population.

PMID- 15148591
TI  - Hydrocephalus and Hirschsprung's disease with a mutation of L1CAM.
AB  - Abnormalities of the L1CAM gene, a member of the immunoglobulin gene superfamily
      of neural-cell adhesion molecules, are associated with X-linked hydrocephalus and
      some allelic disorders. Hirschsprung's disease (HSCR) is characterized by the
      absence of ganglion cells and the presence of hypertrophic nerve trunks in the
      distal bowel. There have been three reports of patients with X-linked
      hydrocephalus and HSCR with a mutation in the L1CAM gene. We report three more
      patients with similar conditions. We suspect that decreased L1CAM may be a
      modifying factor in the development of HSCR.

PMID- 15148590
TI  - Functional impairment of two novel mutations detected in lipoprotein-associated
      phospholipase A2 (Lp-PLA2) deficiency patients.
AB  - Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet
      activating factor (PAF) acetylhydrolase (PAF-AH), is a member of the serine
      dependent class of A2 phospholipases that hydrolyze sn2-ester bonds of fragmented
      or oxidized phospholipids at sites where atherosclerotic plaques are forming.
      Most circulating Lp-PLA2 is bound to low-density lipoprotein (LDL) particles in
      plasma and the rest to high-density lipoprotein (HDL). Deficiency of Lp-PLA2 is a
      predisposing factor for cardiovascular diseases in the Japanese population. We
      describe here two novel mutations of the gene encoding Lp-PLA2, InsA191 and I317N
      in Japanese subjects. The first patient, with partial Lp-PLA2 deficiency, was
      heterozygous for the InsA191 mutation; macrophages from this patient secreted
      only half the normal amount of Lp-PLA2 in vitro. The other patient, who showed
      complete Lp-PLA2 deficiency, was a compound heterozygote for the novel I317N
      mutation and a common V279F mutation; macrophages from that patient failed to
      secrete any Lp-PLA2. Measurement of Lp-PLA2 mass, activity and Western blotting
      verified impaired production and secretion of the enzyme after transfection of
      mutant construct into COS-7 cells. These results indicated that both novel
      mutants, InsA191 and I317N, impair function of the Lp-PLA2 gene.

PMID- 15148592
TI  - Congenital bilateral renal arteriovenous malformation: an unrecognized cause of
      renal failure.
AB  - Congenital renal arteriovenous malformations (AVM) are very rare abnormal
      communications between arteries and veins. These lesions are almost always
      unilateral, predominantly in the right kidney, and usually asymptomatic until
      adulthood. We present a unique case of bilateral renal AVM in a 10-year-old white
      boy who developed renal failure requiring renal transplantation. Microscopic
      sections of an atrophic right and a slightly larger left kidney with tortuous and
      dilated hilar vessels showed elaborate derangement of arteries and veins
      insinuating between lobules. Glomeruli were diffusely enlarged with increased
      number of capillary loops. Glomerular basement membrane reduplication and
      fibrinoid necrosis was focally noted. Electron microscopy demonstrated absence of
      electron-dense deposits or mesangial interposition excluding
      membranoproliferative glomerulonephritis. We believe that the glomerular lesions
      are secondary to congenital renal arteriovenous malformation. To our knowledge,
      bilateral arteriovenous malformation in infancy is not previously described.

PMID- 15148593
TI  - Posttransplant lymphoproliferative disorder presenting as CD30+, ALK+, anaplastic
      large cell lymphoma in a child.
AB  - We report a 15-year-old cardiac transplant recipient who developed a monomorphic
      posttransplant lymphoproliferative disorder (PTLPD) which demonstrated
      morphological and immunohistochemical features of anaplastic large cell lymphoma
      including CD30 and anaplastic lymphoma kinase (ALK) immunopositivity but lacking
      the commonly associated t(2;5) translocation. The neoplastic cells were Epstein
      Barr Virus (EBV)-negative. T-cell PTLPD is an uncommon but recognized late
      complication in solid organ transplant recipients. This is the first reported
      case, to our knowledge, of PTLPD occurring in childhood with an ALK+, CD30+
      anaplastic large cell lymphoma phenotype.

PMID- 15148594
TI  - Finite helical axes of motion are a useful tool to describe the three-dimensional
      in vitro kinematics of the intact, injured and stabilised spine.
AB  - The finite helical-axes method can be used to describe the three-dimensional in
      vitro kinematics of the spine. However, this method still suffers from large
      stochastic calculation errors and poorly conceived visualisation techniques. The
      aim of the present study, therefore, was to improve the currently used finite
      helical axes description, by use of a less error-prone calculation algorithm and
      a new visualisation technique, and to apply this improved method to the study of
      the three-dimensional in vitro kinematics of the spine. Three-dimensional,
      continuous motion data of spinal motion segments were used to calculate the
      position and orientation of the finite helical axes (FHAs). The axes were then
      projected on plane antero-posterior, lateral and axial radiographs in order to
      depict the relation to the anatomy of each individual specimen. A hinge joint was
      used to estimate the measurement error of data collection and axes calculation.
      In an exemplary in vitro experiment, this method was used to demonstrate the
      ability of a prosthetic disc nucleus to restore the three-dimensional motion
      pattern of lumbar motion segments. In the validation experiment with the hinge
      joint, the calculated FHAs were lying within +/-2.5 mm of the actual joint axis
      and were inclined relative to this axis at up to +/-1.5 degrees . In the
      exemplary in vitro experiment, the position and orientation of the FHAs of the
      intact specimens were subject to large inter-individual differences in all
      loading directions. Nucleotomy of the lumbar segments caused the axes to spread
      out, indicating complex coupled motions. The implantation of the prosthetic disc
      nucleus, for the most part, more than reversed this effect: the axes became
      oriented almost parallel to each other. The experiments showed that the present
      improved description of finite helical axes is a valid and useful tool to
      characterise the three-dimensional in vitro kinematics of the intact, injured and
      stabilised spine. The main advantage of this new method is the comprehensive
      visualisation of joint function with respect to the individual anatomy.

PMID- 15148595
TI  - Posterior fixation of subaxial cervical spine fractures in patients with
      ankylosing spondylitis.
AB  - Cervical spine fractures in patients with ankylosing spondylitis are serious and
      potentially lethal injuries with high complication rates. Treatment obstacles
      include long lever arms that generate large forces on any fixation device,
      osteoporosis, and, usually, kyphotic deformity. The Olerud Cervical Fixation
      System (OC), with cervical pedicle screws and rods, offers an opportunity to
      create a biomechanically stable posterior fixation in these complicated cases.
      The present study is a retrospective chart review and a radiological follow-up of
      patients with this diagnosis, treated at our department between 1995 and 2000.
      Nineteen patients (two women) with a mean age of 60 years (32-78 years) were
      included. The fracture levels were predominantly C5-C6 (five patients) and C6-C7
      (five patients). All patients were treated with a long posterior fixation with
      the OC, and in four patients this was combined with an anterior plate fixation.
      One patient with severe lordosis also received a short posterior plate fixation.
      The patients' notes and plain radiographs have been reviewed. Five patients died
      during the post-operative follow-up period; the others had a mean follow-up time
      of 24 months (10-55 months). Eleven patients had no neurological deficits
      preoperatively. One of them developed moderate weakness in his right arm,
      postoperatively, due to a misplaced pedicle screw in the right pedicle of C5.
      However, after extraction of the screw he almost totally recovered in 6 months.
      Eight patients had neurological deficits. Two were paraplegic; two had motor
      weakness combined with sensory deficiency, and four had a sensory deficiency. Two
      of the patients with neurological deficits improved postoperatively, but the
      others were unchanged. Peroperative problems were recorded in five patients; one
      C6 pedicle was perforated, and two patients had pedicles on one or more levels
      that the surgeon was not able to probe. In one of the latter patients, transfacet
      screws were chosen, instead, for one of the levels. Extensive peroperative
      bleeding was encountered in two patients. One deep-wound infection was noted,
      postoperatively, and required surgical drainage, but no patients have been re
      operated due to loosening of the instrument or to healing problems. In
      conclusion, the results of the present study indicate that the OC--and possibly
      other similar long-fixation systems that allow using both pedicle screws and
      lateral mass screws rigidly connected to a rod--is suited for treating subaxial
      cervical spine fractures in patients with ankylosing spondylitis, allowing high
      healing rates.

PMID- 15148597
TI  - On the density-dependence of seed predation in Dipteryx micrantha, a bat
      dispersed rain forest tree.
AB  - We studied the effect of seed density on seed predation by following the fate of
      bat-dispersed Dipteryx micrantha (Leguminosae) seeds deposited under bat feeding
      roosts. The study was conducted in Cocha Cashu biological station, Amazonian
      Peru, during the fruiting period of Dipteryx. Predation of Dipteryx seeds in the
      area is mainly by large to medium-sized rodents. Seed deposits beneath bat
      feeding roosts were monitored for a 13-week period in an 18-ha study area. A
      total of 210 seed deposits were found, and on average, seed predators encountered
      22% of them during any one week. About one-third of the seed deposits escaped
      predation, and those deposits that had relatively few seeds were more likely to
      go unnoticed by rodents than were deposits with many seeds. The mean seed
      destruction rate was 8% per week; deposits with many seeds tended to lose a
      smaller proportion of their seeds to seed predators than did deposits with few
      seeds. Regression tests for the weekly data showed that, at the beginning of the
      observation period, seed predation was not density-dependent. Later, when the
      total seed crop beneath roosts was high, the number of seeds predated per deposit
      was positively density-dependent, while the proportion of seeds predated was
      negatively density-dependent, indicating predator satiation. Seed deposits that
      had been visited by seed predators once had a higher probability of being
      revisited the week after, especially if they contained many seeds when first
      encountered. This indicates that the foraging behavior of rodents may be affected
      by their remembering the location of seed-rich patches.

PMID- 15148598
TI  - Ancient ecology of 15-million-year-old browsing mammals within C3 plant
      communities from Panama.
AB  - Middle Miocene mammals are known from approximately 15 million-year-old sediments
      exposed along the Panama Canal of Central America, a region that otherwise has an
      exceedingly poor terrestrial fossil record. These land mammals, which represent a
      part of the ancient terrestrial herbivore community, include an oreodont
      Merycochoerus matthewi, small camel-like protoceratid artiodactyl Paratoceras
      wardi, two horses Anchitherium clarencei and Archaeohippus sp., and two rhinos
      Menoceras barbouri and Floridaceras whitei. Bulk and serial carbon and oxygen
      isotope analyses of the tooth enamel carbonate allow reconstruction of the
      ancient climate and ecology of these fossil mammals. Ancient Panama had an
      equable climate with seasonal temperature and rainfall fluctuations less than
      those seen today. The middle Miocene terrestrial community consisted
      predominantly, or exclusively, of C3 plants, i.e., there is no evidence for C4
      grasses. Statistically different mean carbon isotope values for the mammalian
      herbivores indicate niche partitioning of the C3 plant food resources. The range
      of individual carbon isotope analyses, i.e., delta13C from -15.9 to -10.1 per
      thousand, indicates herbivores feeding on diverse plants from different habitats
      with extrapolated delta13C values of -29.9 to -24.2 per thousand, possibly
      ranging from dense forest to more open country woodland. The ecological niches of
      individual mammalian herbivore species were differentiated either by diet or body
      size.

PMID- 15148596
TI  - Outcome of patients with antenatally detected pelviureteric junction obstruction.
AB  - We investigated the outcome of patients with antenatally detected pelviureteric
      junction (PUJ) obstruction treated either conservatively or surgically. The
      series comprised 68 such patients, 54 with unilateral obstruction. Of the
      unilateral cases, 22 units were treated conservatively, 21 underwent early and 11
      late surgery. Of the bilateral cases, 18 units were treated conservatively, 9
      underwent early pyeloplasty, whereas 1 underwent later surgery. Among the
      conservatively treated unilateral cases, none of the patients' good renal
      function deteriorated during follow-up. In the group with early surgery, the
      primary good function remained unchanged in all. In some patients, moderate
      function improved after early pyeloplasty, but in patients with poor function no
      improvement occurred. Of patients who underwent late pyeloplasty, primary good
      renal function remained unchanged in all except 1, although it had deteriorated
      to moderate function in some before surgery. In all except 1 patient with
      bilateral obstruction treated conservatively, both the grade of hydronephrosis
      and split function remained unchanged. In most patients the outcome of
      antenatally detected unilateral PUJ obstruction with initially good renal
      function, whether treated conservatively or surgically, seems favorable. Some
      patients with moderate function might benefit from pyeloplasty. In kidneys with
      poor function, recovery may be minimal despite pyeloplasty.

PMID- 15148599
TI  - Reproductive development according to elevation in a seasonally breeding male
      songbird.
AB  - Seasonal temperate zone breeders respond to increasing day length to anticipate
      the approach of spring breeding conditions. Other (supplementary) environmental
      cues, such as temperature and precipitation, were historically thought to play
      unimportant roles in reproductive timing. We demonstrate variation in
      reproductive timing across small geographic distances by examining the vernal
      testicular recrudescence of adult song sparrows (Melospiza melodia morphna)
      breeding in coastal (0-10 m elevation) and montane (280-1220 m elevation)
      habitats. Each year, these birds experienced the same photoperiod, but were
      exposed to different supplementary cues that varied with altitude. Coastal birds
      experienced warmer and more stable temperatures during late winter and early
      spring than did montane birds. We measured bud opening, emergence of new green
      shoots, and arthropod biomass to monitor the pace of spring's approach. New
      spring shoots emerged 2 months earlier on the coast than in the mountains and
      buds on flowering trees and shrubs also tended to open earlier at the coast.
      Arthropod biomass was similar in both the mountains and the coast during early
      spring, and began to increase in early summer. Reproductive morphology (i.e.
      testis volume and cloacal protuberance length) developed up to 2 months earlier
      on the coast than in the mountains. Testicular recrudescence occurred earlier on
      the coast in most years and proceeded at a faster rate in 1 year. Circulating
      levels of luteinizing hormone, follicle stimulating hormone and prolactin
      increased through the season, but did not correlate with differences between
      sites. Both populations responded similarly when exposed to identical
      photoperiodic cues in the laboratory. Therefore, we suggest that an integrated
      response to cues characteristic of location and elevation account for differences
      in patterns measured in the field.

PMID- 15148600
TI  - Drought responses of conifers in ecotone forests of northern Arizona: tree ring
      growth and leaf delta13C.
AB  - We sought to understand differences in tree response to meteorological drought
      among species and soil types at two ecotone forests in northern Arizona, the
      pinyon-juniper woodland/ponderosa pine ecotone, and the higher elevation, wetter,
      ponderosa pine/mixed conifer ecotone. We used two approaches that provide
      different information about drought response: the ratio of standardized radial
      growth in wet years to dry years (W:D) for the period between years 1950 and 2000
      as a measure of growth response to drought, and delta13C in leaves formed in non
      drought (2001) and drought (2002) years as a measure of change in water use
      efficiency (WUE) in response to drought. W:D and leaf delta13C response to
      drought for Pinus edulis and P. ponderosa did not differ for trees growing on
      coarse-texture soils derived from cinders compared with finer textured soils
      derived from flow basalts or sedimentary rocks. P. ponderosa growing near its low
      elevation range limit at the pinyon-juniper woodland/ponderosa pine ecotone had a
      greater growth response to drought (higher W:D) and a larger increase in WUE in
      response to drought than co-occurring P. edulis growing near its high elevation
      range limit. P. flexilis and Pseudotsuga menziesii growing near their low
      elevation range limit at the ponderosa pine/mixed conifer ecotone had a larger
      growth response to drought than co-occurring P. ponderosa growing near its high
      elevation range limit. Increases in WUE in response to drought were similar for
      all species at the ponderosa pine/mixed conifer ecotone. Low elevation
      populations of P. ponderosa had greater growth response to drought than high
      elevation populations, whereas populations had a similar increase in WUE in
      response to drought. Our findings of different responses to drought among co
      occurring tree species and between low- and high-elevation populations are
      interpreted in the context of drought impacts on montane coniferous forests of
      the southwestern USA.

PMID- 15148601
TI  - Defoliation increases carbon limitation in ectomycorrhizal symbiosis of Betula
      pubescens.
AB  - Boreal forest trees are highly dependent on root-colonizing mycorrhizal fungi.
      Since the maintenance of mycorrhizal symbiosis implies a significant carbon cost
      for the host plant, the loss of photosynthetic leaf area due to herbivory is
      expected to reduce the host investment in mycorrhizae. We tested this hypothesis
      in a common garden experiment by exposing ectomycorrhizal white birch (Betula
      pubescens Ehrh.) seedlings to simulated insect defoliation of 50 or 100%
      intensity during either the previous or the current summer or repeatedly during
      both seasons before harvest. The shoot and root growth of the seedlings were
      distinctly reduced by both 100% defoliation and repeated 50% defoliation, and
      they were more strongly affected by previous-year than current-year defoliation.
      The root to shoot ratio significantly decreased after 100% defoliation,
      indicating reduced proportional allocation to the roots. Ergosterol concentration
      (i.e. fungal biomass) in the fine roots decreased by 100% defoliation conducted
      either in the year of harvest or in both years. No such decrease occurred
      following the 100% defoliation conducted in the previous year, indicating the
      importance of current photosynthates for fungal symbionts. The trend was similar
      in the colonization percentage of thick-mantled mycorrhizae in the roots, the
      most marked decline occurring in the repeatedly defoliated seedlings. The present
      results thus support the prediction that the plant investment in ectomycorrhizae
      may decline as a response to foliage loss. Moreover, the colonization percentage
      of thick-mantled mycorrhizae correlated positively with the ratio of leaf to
      heterotrophic plant biomass in the defoliated birch seedlings, but not in the
      control ones. This tends to indicate a stronger carbon limitation of
      ectomycorrhizal colonization in defoliated seedlings.

PMID- 15148602
TI  - Induced resistance in intertidal macroalgae modifies feeding behaviour of
      herbivorous snails.
AB  - Herbivory in terrestrial and marine systems can induce changes in plant chemistry
      affecting the foraging behaviour of herbivores. A model based on terrestrial
      plant-herbivore interactions predicts herbivory-induced changes in leaf chemistry
      to be manifested in (1) increased herbivore mobility, (2) increased feeding
      dispersal and (3) reduced tissue consumption by herbivores. This study is the
      first to demonstrate that herbivory-induced changes in the tissue chemistry of
      the brown seaweed Ascophyllum nodosum elicit the same response in the feeding
      behaviour of the gastropod Littorina obtusata as predicted for herbivorous
      insects, providing good evidence for the model's validity across different
      ecosystems. The potential benefit of increased feeding dispersal to terrestrial
      plants as suggested by the model is the prevention of concentrated damage to
      apical tissues thereby preserving the plant's ability to compete for light; A.
      nodosum does not conform to these predictions. Increased dispersal of feeding
      damage on A. nodosum away from primary frond tissues would reduce the likelihood
      of frond breakage implying a fitness benefit of induced resistance.

PMID- 15148603
TI  - Constraints to seedling success of savanna and forest trees across the savanna
      forest boundary.
AB  - Tropical savannas and closed forests are characterized by distinct tree
      communities, with most species occurring almost exclusively in only one of the
      two environments. The ecology of these two groups of species will largely
      determine the structure and dynamics of the savanna-forest boundary, but little
      is known about the ecological and physiological differences that might control
      their distributions. We performed field and nursery experiments to compare
      seedling establishment success, predawn leaf water potential, biomass allocation,
      and root carbohydrate concentration of congeneric species, each composed of one
      savanna species and one forest species. Seedling establishment of savanna and
      forest species responded differently to vegetation cover, with forest species
      having lowest establishment success in the open savanna and savanna species
      having lowest success in forest. Subsequent survival followed similar patterns,
      resulting in even greater differences in cumulative success. The low survival of
      forest species in the savanna appears related to drought stress, as seedlings of
      forest species had lower predawn leaf water potential than savanna species.
      Seedlings of savanna species had greater root: shoot ratios and root total
      nonstructural carbohydrate (TNC) concentration, particularly among evergreen
      genera. Among evergreen genera, root TNC per shoot mass, which may largely
      determine resprout capacity, was seven times higher in savanna species than
      forest species. Although water availability and microclimate may reduce the
      success of forest species, these factors appear unable to completely exclude
      forest seedling establishment in savanna. Fire, on the other hand, appears to be
      a much more absolute constraint to success of forest species in savanna.

PMID- 15148604
TI  - Association between up-regulation of stress-responsive genes and hypomethylation
      of genomic DNA in tobacco plants.
AB  - Transcripts that specifically accumulate in transgenic tobacco plants expressing
      an anti-sense construct for a tobacco type I DNA methyltransferase, NtMET1, were
      screened by the differential display method. Of the 31 genes identified, 16
      encoded proteins with known functions; ten of these were related to biotic and
      abiotic stress responses, and the other six to cellular functions. In order to
      examine whether expression of these genes is correlated with DNA methylation
      status under natural stress conditions, a pathogen-responsive gene (NtAlix1) was
      selected as representative, and assayed for transcript induction and genomic
      methylation in tobacco plants infected with tobacco mosaic virus (TMV). In
      inoculated leaves of wild-type plants, NtAlix1 transcripts began to accumulate 12
      h after the onset of the hypersensitive response (HR), and levels remained high
      for up to 24 h. Changes in the methylation status at the locus became obvious 24
      h later, as detected by digestion of genomic DNA with a methylation-sensitive
      restriction enzyme. The results suggest that the level of DNA methylation may
      change in response to external stresses, and that this is closely related to the
      activation of stress-responsive genes.

PMID- 15148605
TI  - Mutational analysis of the binding affinity and transport activity for N
      acetylglucosamine of the novel ABC transporter Ngc in the chitin-degrader
      Streptomyces olivaceoviridis.
AB  - The highly differentiated bacterium Streptomyces olivaceoviridis efficiently
      hydrolyses chitin, a highly abundant natural polysaccharide, to low molecular
      weight products including N-acetylglucosamine (NAG) and N,N' -diacetylchitobiose
      (chitobiose). NAG is taken up by a PTS (phosphoenolpyruvate-dependent
      phosphotransferase system) which includes the PtsC2 protein, and via the ABC (ATP
      binding cassette) transporter Ngc, which itself includes the substrate-binding
      protein NgcE. This is at present the only ABC transporter which is known to
      mediate specific uptake of NAG (K(m) 0.48 microM, V(max) 1.3 nmol/min/mg dry
      weight) and is competitively inhibited by chitobiose (K(i) 0.68 microM). The
      latter finding suggests that the Ngc system transports both NAG and chitobiose
      efficiently. To identify amino acid residues required for the function of NgcE,
      either the wild-type or one of several mutant forms of the ngcE gene was
      introduced into the strain S. olivaceoviridis DeltaNgcE/DeltaPtsC1/DeltaPtsC2,
      which lacks both functional transport systems for NAG, and chromosomal
      recombinants were selected. Based on the in vivo transport parameters of the
      recombinants, and the in vitro binding characteristics of the corresponding
      purified proteins, the following conclusions can be drawn. (1) Replacement of the
      C-terminally located residue Y396 by A (Y396A) has little effect on ligand
      binding or transport parameters. The W395A mutation also induced little change in
      the substrate affinity in vitro, but it led in vivo to a marked increase (11
      fold) in K(m), and enhanced V(max) (by 1.5 fold). (2) The amino acids Y201 and
      W280 both contribute (51% and 38%) to the ligand-binding capacity of NgcE. They
      are both very important for the in vivo function of the complete transport
      apparatus; strains expressing either Y201A or W280A show drastically (100 or 150
      times) enhanced K(m) values. (3) The concomitant presence of either Y200 and W280
      or Y201 and W280 is essential for the function of NgcE. (4) Y201 is located
      within a tyrosyl-rich motif. This has been found to share some features with the
      ligand-binding site of amelogenins (enamel matrix proteins), which interact with
      NAG residues in glycoconjugates. In addition, it is distantly related to the
      ligand-binding site(s) in the plant-lectins UDA ( Urtica dioicaagglutinin,
      specific for NAG and its oligomers) and WGA (wheat germ agglutinin, which
      recognises a motif comprising three consecutive NAG residues).

PMID- 15148606
TI  - Functional stability of the aristaless gene in appendage tip formation during
      evolution.
AB  - The appendages of an insect are subdivided into distinct segments or podomeres.
      Many genes responsible for the regionalization of the growing limb into
      subdomains have been isolated from Drosophila. So far, only one gene is known in
      the leg that is solely required for specifying the distal-most pattern element
      the pretarsal claw. In Drosophila, the gene aristaless is expressed in the centre
      of the antennal and leg imaginal disc that represents the most distal position of
      appendages, and in a proximal region. When Drosophila aristaless function is
      impaired, antennae and legs develop without their distal-most structures-the
      arista and the claw. We describe here the analysis of aristaless in the beetle
      Tribolium-an insect that shows a different, more ancestral mode of appendage
      formation than Drosophila. In Tribolium, appendages grow out continuously during
      embryogenesis, and no imaginal discs are formed. Tribolium aristaless (Tc-al)
      expression starts midway during appendage elongation, and is seen in a distal and
      a proximal position of head and trunk appendages. At the end of embryogenesis, Tc
      al is seen in four expression domains in the leg, in the dorsal epidermis, and
      ventrally in every segment in lateral groups of cells, presumably the
      histoblasts. Like in the Drosophila adult, Tc-al is required in the larva for the
      formation of the most distal structures of the leg and the antenna as revealed by
      RNAi experiments. We conclude that aristaless is evolutionarily robust, meaning
      that it has retained its expressional and functional characteristics, although a
      heterochronic change of the process of appendage elongation took place towards
      the evolution of the highly derived diptera.

PMID- 15148607
TI  - Cellular expression of murine Ym1 and Ym2, chitinase family proteins, as revealed
      by in situ hybridization and immunohistochemistry.
AB  - Ym is one of the chitinase family proteins, which are widely distributed in
      mammalian bodies and can bind glycosaminoglycans such as heparin/heparan sulfate.
      Ym1 is a macrophage protein produced in parasitic infections, while its isoform,
      Ym2, is upregulated in lung under allergic conditions. In the present study, we
      revealed the distinct cellular expression of Ym1 and Ym2 in normal mice by in
      situ hybridization and immunohistochemistry. Ym1 was principally expressed in the
      lung, spleen, and bone marrow, while Ym2 was found in the stomach. Ym1-expressing
      cells in the lung were alveolar macrophages, and the immunoreactivity for Ym1 was
      localized in rough endoplasmic reticulum. In the spleen, Ym1-expressing cells
      gathered in the red pulp and were electron microscopically identified as immature
      neutrophils. In the bone marrow, immature neutrophils were intensely
      immunoreactive, but lost this immunoreactivity with maturation. Moreover, needle
      shaped crystals in the cytoplasm of macrophages, which formed erythroblastic
      islands, also showed intense Ym1 immunoreactivity. Ym2 expression was restricted
      to the stratified squamous epithelium in the junctional region between
      forestomach and glandular stomach. The function of Ym1 and Ym2 is still unclear;
      however, the distinct cellular localization under normal conditions suggests
      their important roles in hematopoiesis, tissue remodeling, or immune responses as
      an endogenous lectin.

PMID- 15148608
TI  - Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced
      apoptosis in human keratinocytes and HeLa cells.
AB  - Caspases, members of the cysteine protease family, execute UVB-induced apoptosis
      in several cell lines and keratinocytes. Several researchers investigating UVB
      induced apoptosis have demonstrated a dose-dependent protective effect of the
      synthetic peptide caspase inhibitor zVAD-fmk. However, zVAD-fmk displays a dose
      dependent protective effect against UVB-induced apoptosis, even at doses higher
      than those required to block all known proapoptotic caspases. In addition, it is
      known that zVAD-fmk also inhibits other cysteine proteases including cathepsins
      and calpains, and these proteases have recently been demonstrated to play a role
      in the execution of programmed cell death induced by other stimuli, e.g. TNF
      alpha. The purpose of the present study was therefore to investigate whether
      inhibitors of cysteine cathepsins and calpains could prevent UVB-induced
      apoptosis in HeLa cells and keratinocytes. This was done by investigating the
      effect of the irreversible cysteine protease inhibitor zFA-fmk, the cathepsin B
      inhibitor CA-074-Me and the calpain inhibitor ALLN on the viability of UVB
      irradiated human keratinocytes and HeLa cells. At concentrations of 10 microM and
      above zVAD-fmk conferred partial dose-dependent protection against UVB-induced
      apoptosis in HeLa cells and keratinocytes. Moreover, caspase-3 activity was
      completely blocked at zVAD-fmk concentrations of 1 microM in HeLa cells. This
      indicates that caspase-independent mechanisms could be involved in UVB-induced
      apoptosis. However, the protease inhibitors zFA-fmk, CA-074-Me and ALLN all
      failed to prevent UVB-induced apoptosis in HeLa cells and keratinocytes. In
      conclusion, the protective effect of zVAD-fmk at high concentrations indicates
      that other proteases than caspases are active in the execution of UVB-induced
      apoptosis but further studies are needed to identify these proteases.

PMID- 15148609
TI  - Differentiation-regulated expression of Toll-like receptors 2 and 4 in HaCaT
      keratinocytes.
AB  - Toll-like receptors (TLRs) play an important role in the recognition of pathogens
      in keratinocytes. In this study, we investigated whether the differentiation
      state of HaCaT keratinocytes correlates with the expression of TLR2 and TLR4
      genes. The expression levels of TLR2 and TLR4 in a HaCaT differentiation model
      system were determined using quantitative real-time RT-PCR (Q-RT-PCR) and flow
      cytometry. The progression of keratinocyte differentiation was monitored by
      determining the level of involucrin gene expression using Q-RT-PCR. The
      expression levels of TLR2 and TLR4 increased with the stage of differentiation
      and there were strong correlations between the expression level of the involucrin
      gene and those of the TLR2 gene ( r=0.809, P<0.0001) and the TLR4 gene ( r=0.568,
      P<0.02). Increased cell surface expression of TLR2 and TLR4 was also found in
      differentiated HaCaT keratinocytes by flow cytometric analysis. Our findings
      suggest that upregulation of TLR expression during differentiation in
      keratinocytes could be a part of the differentiation process of keratinocytes and
      could have biological significance in protecting skin against microbes.

PMID- 15148610
TI  - Treatment of missed posterior dislocation of the shoulder by delayed open
      reduction and glenoid reconstruction with corticocancellous iliac bone autograft.
AB  - This is a report of a 2-year follow-up of a missed posterior shoulder dislocation
      treated with open reduction and glenoid reconstruction with corticocancellous
      iliac bone autograft. In such cases, this treatment option may be an alternative
      to hemiarthroplasty of the shoulder.

PMID- 15148611
TI  - Bone morphogenetic protein 2 accelerates osteointegration and remodelling of
      solvent-dehydrated bone substitutes.
AB  - INTRODUCTION: lt was the purpose of this study to investigate how bone
      morphogenetic protein 2 (BMP-2) influences remodelling and the biomechanics of
      solvent-dehydrated bone in the long run. Furthermore, the early influence of this
      growth factor on the substitute was investigated. MATERIALS AND METHODS: Using a
      weight-bearing animal model, solvent-dehydrated bone was implanted in the tibial
      head of merino sheep ( n=12) after being loaded with BMP-2 (100 microg/100
      microl). At 4 weeks ( n=6) and 9 months ( n=6) after surgery, histomorphological,
      histomorphometrical and biomechanical investigations were performed. RESULTS: At
      9 months after implantation of BMP-2-loaded specimens, the bone per tissue volume
      was high, with levels above those of physiological cancellous bone. The amount of
      remaining solvent-dehydrated bone was markedly decreased, and in contrast, the
      amount of newly formed bone was extremely high. The specimen degradation had
      already occurred within the first 4 weeks after implantation, showing no further
      impact throughout the 9-month period. Biomechanical investigations at 9 months
      after implantation demonstrated a yield strength which achieved levels at least
      equivalent to physiological cancellous bone. BMP-2 showed no significant impact
      on the biomechanical properties after 4 weeks, compared to specimens prior to
      implantation. CONCLUSION: BMP-2 predominantly has an impact on the early implant
      degradation as well as bone formation, which leads to an almost completed bone
      remodelling of the solvent-dehydrated specimen within the study period of 9
      months.

PMID- 15148612
TI  - Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and
      meningiomas.
AB  - Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with
      enhanced malignant potential of many human tumor types including glioblastoma
      multiforme. The significance of EGFR expression in meningiomas is, however,
      unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain
      tumors are sparse. In this study, the expression of the EGFR family members was
      analyzed in relation to various parameters for the clinical importance of these
      receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time
      reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high
      grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade
      gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas.
      Immunohistochemistry showed significantly higher EGFR protein expression in high
      grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression
      was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all
      gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade
      gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real
      time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of
      the tumors. ErbB3 was detected in only one of the meningiomas analyzed.
      Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas.
      An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a
      significantly decreased overall survival for patients with high EGFR protein
      expression (P= 0.04). The high ErbB4 expression in low-grade compared to high
      grade gliomas might suggest that ErbB4 acts as a suppressor of malignant
      transformation in brain tumors, which is in line with previous studies in other
      tumor types.

PMID- 15148613
TI  - Acquired tracheo-esophageal fistulas caused by button battery lodged in the
      esophagus.
AB  - Esophageal impacting of button batteries must be distinguished from impacting of
      other foreign bodies because of their severe complications. We present a 2.5-year
      old girl who had an acquired tracheo-esophageal fistula (TEF) caused by a
      calculator battery lodged in her esophagus. We also review the literature and
      assess the applicability of multislice CT and its possible advantages in children
      with acquired TEF.

PMID- 15148614
TI  - Oesophageal atresia: what has changed in the last 3 decades?
AB  - The aim of the study was to analyse the outcomes of children born with
      oesophageal atresia over the last 3 decades. The records of 104 patients born
      between 1973 and 1999 were reviewed retrospectively. To evaluate changes over
      time, the analysis was done for three consecutive time periods: 1973-79, 1980-89,
      and 1990-99. Mean birth weight was 2553 g (SD 640), and mean gestational age was
      39 weeks (SD 4). Forty-two newborns (40%) had one or more associated congenital
      malformations, and 30% had associated cardiac malformations. There was no change
      in incidence of associated anomalies over the three time periods studied.
      Mortality of patients decreased from 33% to 14% (p = 0.048). There was a
      significant association between the presence of a major cardiac malformation and
      survival (survival: 88% vs. 57%, p = 0.004). Analysing the three different time
      periods separately reveals that cardiac disease was not a significant risk factor
      in the first period but became significant in the period from 1980-99 (relative
      risk: 6.76, 95% CI 1.44-31.77). Birth weight was significantly higher in infants
      who survived (2626 g, SD 642) compared with those who died (2290, SD 570, p =
      0.028). This effect, however, is mainly based on the difference during the first
      period and is lost later. Early and late postoperative complications occurred in
      44/102 patients. Strictures developed in 33/91 patients who survived the first
      month of life (33%). The rate of symptomatic strictures decreased significantly
      over the three time periods, from 50% to 23% (p = 0.022). In summary, this study
      shows no significant change in patient characteristics over the last 3 decades,
      but mortality and postoperative complication rates decreased, and associated
      cardiac anomalies became the far most important risk factor for mortality.

PMID- 15148616
TI  - Anatomical repair of exstrophy bladder.
AB  - An anatomical repair of bladder exstrophy was done in ten patients (six females
      and four males, aged 1.5-6 months. We describe our method of exstrophy with
      epispadias repair done in a single stage achieving anatomical closure including
      relocating skin from an infraphallic to a supraphallic position. The cosmetic and
      functional results are evaluated. The advantages of this technique are described.

PMID- 15148617
TI  - Primary tumours of the liver in children: an African perspective.
AB  - Primary tumours of the liver present diagnostic and management difficulties. In
      Africa, outcomes reflect limitations imposed by comorbidity and lack of
      resources, both human and material, for major liver resection. Whilst
      hepatoblastoma and hepatocellular carcinoma can be readily distinguished on
      clinical and biochemical grounds, there is a high incidence of sarcomatous
      tumours that mandate biopsy. In our experience, hepatocellular carcinoma in
      childhood is a lethal condition, usually bilateral and associated with hepatitis
      B infection. Sarcomatous tumours are often resectable but have a high rate of
      local recurrence. Hepatoblastoma is a surgically curable tumour in many patients.
      Resection for benign liver tumours can be safely accomplished and augments
      institutional experience with major liver surgery.

PMID- 15148615
TI  - Advances in the treatment of oesophageal atresia over three decades: the 1970s
      and the 1990s.
AB  - Oesophageal atresia management has evolved alongside the development of
      paediatric surgery. An analysis of a 30-year prospective collection of
      oesophageal atresia cases treated at the Royal Alexandra Hospital for Children,
      NSW, Australia is presented. There has been a dramatic change in the surgical
      approach. Fewer infants are undergoing operations of cervical oesophagostomy,
      gastrostomy and oesophageal replacement. More, including fragile infants, are
      surviving with a repaired native oesophagus. Fewer infants are suffering
      morbidity secondary to anastomotic leak. The progression in treatment has been
      enabled by improved neonatal support due to advances in neonatology, neonatal
      anaesthesia, nutritional support and antimicrobial therapy. Oesophageal atresia
      treatment and outcome has changed markedly over three decades. Cooperative multi
      centre database development is now required to provide data in order to further
      refine treatment for clinical challenges that remain.

PMID- 15148619
TI  - Delayed repair of large myelomeningoceles.
AB  - INTRODUCTION: Repair of myelomeningoceles larger than 5 cm in diameter is not
      easy. We describe a simple technique. PATIENTS AND METHODS: The patients with a
      large myelomeningocele sac were included in this study. Ten patients with a large
      myelomeningocele underwent surgical repair using this technique. The skin was
      incised in the midline proximal to the myelomeningocele sac. The incision was
      carried caudally and away from the midline to open the sac after identifying the
      fascia. The incision is carried circumferentially around the neural placode and
      the skin is saved as much as possible. About a 1-cm-width of the dura mater
      beneath the skin is left to ease the subcutaneous suturing. The dura is sutured
      in the midline. The skin is undermined bilaterally in the plane between the
      muscle and subcutaneous fat and closed with interrupted sutures in the midline.
      CONCLUSION: This simple technique is appropriate for the closure of large
      myelomeningoceles and does not need more extensive and complex procedures.

PMID- 15148618
TI  - Juvenile colorectal polyps in children: experience in Pakistan.
AB  - Juvenile colorectal polyps are the most common cause of pediatric hematochezia
      and contribute to significant morbidity if not treated early. This report
      describes an experience with juvenile colorectal polyps in children (< or =14
      years) from Pakistan. In a 3-year period, 154 polyps were documented in 129
      children. The mean age at presentation was 5.2 years, with a male predominance.
      Most children presented with painless rectal bleeding (+/-13 months) associated
      with other symptoms, such as protrusion of a mass through the anus, diarrhea, and
      recurrent abdominal pain. Anemia was observed in 54 children, of whom 14 (26%)
      required blood transfusion before intervention. Diagnosis was made by digital
      rectal examination, proctosigmoidoscopy, and barium enema. The average distance
      of a colorectal polyp was 4 cm from the anal verge. In 108 (84%) children the
      polyps were solitary, whereas 21 patients had more than one polyp (maximum three)
      at different locations in the rectosigmoid area. All polyps were successfully
      removed by proctosigmoidoscopy. Histological examination revealed dysplastic
      changes in one case, while the rest were inflammatory. Recurrence occurred in
      seven children within 1 year of initial removal. Juvenile colorectal polyps
      contribute to a substantial morbidity in children and do carry a minimal risk of
      developing dysplastic changes, and therefore should be removed early.

PMID- 15148620
TI  - Arterio-embolic ischemic stroke in children with moyamoya disease.
AB  - INTRODUCTION: Moyamoya (MM) disease is a rare steno-occlusive cerebrovascular
      disease known to occur in children and adults. The most serious complications in
      children are developmental delay and mental retardation due to recurrent
      hemodynamic stroke. CASES: We report two pediatric patients without coagulopathy
      who suffered from severe arterio-embolic ischemic complications despite
      antiplatelet medication. DISCUSSION: These observations underline the potential
      impact of cerebral thromboembolism on the pathophysiology of the stroke and thus
      on the treatment of children with MM disease.

PMID- 15148621
TI  - Comparative study of the heterophil phagocytic function in young and old ring
      doves (Streptopelia risoria) and its relationship with melatonin levels.
AB  - A functional connection between the pineal gland (via the hormone melatonin) and
      the immune system has been suggested. In our previous results in the ring dove,
      we observed diurnal oscillations in the levels of this neurohormone in young
      animals and a decline in its plasma levels with advancing age (which is
      accompanied by the absence of diurnal rhythm). We also noted enhanced phagocytic
      activity of heterophils from old animals after in vitro incubation with both
      physiological and pharmacological doses of melatonin. Here, we evaluate the
      functional capacity of ring dove (Streptopelia risoria) heterophils in young (2
      years of age) and old (8 years and more) animals at different times of day (0:00,
      10:00 and 16:00, the times when the maximum, minimum, and mean values,
      respectively, of melatonin levels are observed in young animals). The phagocytic
      capacities for the ingestion of latex beads and Candida albicans were evaluated,
      as well as the oxidative metabolism which accompanies phagocytosis. At all three
      times of day studied, the heterophil phagocytic function with both latex and C.
      albicans was significantly greater in the young than in the old animals, and in
      the young animal cells it was significantly higher at 0:00. In addition, in the
      presence of latex beads, there was a significant decline at 10:00 and 0:00 of
      superoxide anion levels in the young animals relative to the old. In the young
      animals, there was a decline at 0:00 in comparison with both 10:00 and 16:00, and
      in the old animals there was a decline at both 0:00 and 16:00 compared with
      10:00. These results could be due, at least in part, to the absence of a diurnal
      rhythm of melatonin in old animals, and to an enhancing effect of that hormone on
      young animals' heterophil phagocytic function, which would also neutralize the
      oxidative stress deriving from this immune function.

PMID- 15148622
TI  - Functional magnetic resonance imaging for neurosurgical planning in
      neurooncology.
AB  - Functional magnetic resonance imaging (fMRI) is a non-invasive technique that is
      widely available and can be used to determine the spatial relationships between
      tumor tissue and eloquent brain areas. Within certain limits, this functional
      information can be applied in the field of neurosurgery as a pre-operative
      mapping tool to minimize damage to eloquent brain areas. In this article, we
      review the literature on the use of fMRI for neurosurgical planning. The issues
      addressed are: (1) stimulation paradigms, (2) the influence of tumors on the
      blood oxygenation level-dependent (BOLD) signal, (3) post-processing the fMRI
      time course, (4) integration of fMRI results into neuronavigation systems, (5)
      the accuracy of fMRI and (6) fMRI compared to intra-operative mapping (IOM).

PMID- 15148623
TI  - Characterization of small pulmonary nodules by CT.
AB  - Small pulmonary nodules with diameters </=10 mm are very frequent findings at CT
      examinations. Despite the traditional opinion that every pulmonary nodule should
      be considered malignant until proven otherwise, the vast majority of small
      lesions are benign, and therefore biopsy may not be necessary in all cases.
      During the last few years, several CT-based methods have been developed to
      differentiate between benign and malignant lesions non-invasively. A negative
      quantitative contrast-enhanced CT is a strong predictor for benignity. Repeat
      nodule volume measurements at short-term follow-up CT examinations can detect
      growth suggesting malignancy. Limitations and potential pitfalls of these methods
      must be observed to avoid false negative test results leading to delayed
      diagnosis and treatment of malignant tumours. An algorithm for diagnostic workup
      of incidentally detected small pulmonary nodules in subjects without known
      malignancy is proposed in this article.

PMID- 15148624
TI  - Alternative splicing of transcripts of the transposon Restless is maintained in
      the foreign host Neurospora crassa and can be modified by introducing mutations
      at the 5' and 3' splice sites.
AB  - The primary transcript of the transposon Restless from Tolypocladium inflatum
      undergoes an unusual mechanism of alternative splicing by employing either of two
      3' "CAG" splice sites. These are separated by only four nucleotides, thus
      generating two different splice products, which differ in their coding capacity.
      To analyse whether this alternative splicing occurs in its natural host
      exclusively, we introduced the transposon into the heterologous host Neurospora
      crassa. In addition to the wild -type transposon sequence, transposon sequences
      mutagenised in vitro with modified 5' and 3' intron splice sites were generated.
      RNA was isolated from transformants and RT-PCR was performed with specific
      oligonucleotides flanking the intron sequence. Alternative splicing was analysed,
      employing a simple test procedure based on the convenient presence of a BamHI
      restriction site between both splice sites. The ratio of alternative splicing
      seems to be influenced by both the 5' and the 3' splice site, as mutations at
      either position influence the ratio of alternative splice products. At the 5'
      splice site, mutating the first "C" has a strong effect on the ratio of
      alternative splicing, while mutating the second "C" has little or no effect.
      Similarly, at the 3' splice site, only mutations at the first 3' "CAG" change the
      ratio of alternative splicing. It appears that alternative splicing of the
      Restless intron is not host-specific, but is influenced by the intron splice site
      sequences themselves.

PMID- 15148625
TI  - Late-onset delayed excretion of methotrexate.
AB  - Pleural effusions, ascites, and renal dysfunction decrease the plasma excretion
      of methotrexate (MTX). However, it is not known what effect these complications
      have on MTX clearance when they arise after the plasma MTX concentration has
      fallen to an undetectable level. We describe the clinical course and
      pharmacokinetics of MTX in a patient with acute lymphoblastic leukemia who
      experienced pleural effusions, ascites, and renal failure during the weeks after
      treatment with high-dose MTX (1.63 g/m2 i.v. over 24 h). The patient's normal
      initial MTX clearance rate (107 ml/min/m2) was consistent with his undetectable
      plasma level of MTX on day 9 after the infusion. His plasma MTX concentration
      then gradually increased as his renal function declined, reaching a peak of 0.72
      microM on day 15. This unusual finding of an undetectable plasma MTX
      concentration that subsequently rose to persistent, potentially toxic levels was
      explained only by a pharmacokinetic model that accounted both for a third space
      at the time of treatment and for the subsequent decrease in the systemic
      elimination rate. Therefore, the finding of a physiologic third space during MTX
      administration combined with the detection of renal dysfunction in the following
      weeks should be an indication for prolonged therapeutic drug monitoring.

PMID- 15148626
TI  - A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in
      combination with gemcitabine for patients with advanced cancer.
AB  - PURPOSE: 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), a new and
      potent inhibitor of ribonucleotide reductase (RR), increases the cellular uptake,
      DNA incorporation, and cytotoxicity of gemcitabine in tumor cell lines. A phase I
      trial was initiated to determine the safety profile and maximum tolerated doses
      of 3-AP and gemcitabine when used in combination in patients with advanced
      cancer. STUDY DESIGN: 3-AP and gemcitabine were administered on days 1, 8, and 15
      of each 28-day cycle. Initially, 3-AP was infused over 2 h at a fixed dose of 105
      mg/m(2). Gemcitabine was given over 30 min beginning no less than 1 and no more
      than 4 h after 3-AP. The first cohort received 3-AP alone in the first cycle.
      Subsequently, the gemcitabine dose was escalated beginning at 600 mg/m(2) in
      cohorts of three to six patients. Following the gemcitabine 1000 mg/m(2) dose
      level, the study was amended to determine if the 3-AP dose could be escalated
      above 105 mg/m(2). RESULTS: 3-AP at 105 mg/m(2) administered over 2 h followed in
      1-4 h by gemcitabine at 1000 mg/m(2) produced a toxicity profile similar to that
      expected for gemcitabine alone at the same dose. When the dose of 3-AP was
      escalated to 140 and 185 mg/m(2) administered over 2 h and subsequently over 4 h,
      acute hypotension, hypoxia, and EKG changes including non-specific ST-T wave
      changes and mild QT prolongation were observed, and one patient with underlying
      diffuse coronary artery disease had an asymptomatic myocardial infarction. 3-AP
      was shown to cause mild, reversible methemoglobinemia. Average end-of infusion
      serum concentrations for 3-AP at all doses were within the range capable of
      enhancing gemcitabine cytotoxicity in vitro. Gemcitabine plasma concentrations at
      end-of-infusion and elimination half-life were consistent with values reported in
      the literature. Among 22 evaluable patients, one complete response and two
      partial responses were observed, and an additional patient had prolonged
      stabilization of a large liver metastasis. CONCLUSIONS: 3-AP at 105 mg/m(2)
      infused over 2-4 h followed by gemcitabine at 1000 mg/m(2) on a days 1, 8, and 15
      schedule every 28 days was generally well-tolerated and had a toxicity profile
      similar to that of gemcitabine alone. 3-AP produced mild to modest
      methemoglobinemia, which could cause acute symptoms in patients with limited
      pulmonary or cardiovascular reserve. The combination demonstrated antitumor
      activity and merits further exploration in phase II trials.

PMID- 15148627
TI  - Tumor lysis syndrome following docetaxel therapy for extensive metastatic
      prostate cancer.
AB  - Tumor Lysis Syndrome (TLS) is characterized by biochemical changes due to rapid
      tumor lysis of malignant cells, usually after chemotherapy. Typically it is seen
      in patients with hematologic malignancies sensitive to chemotherapy within days
      of receiving chemotherapy. Recently Baeksgaard and Sorensen reviewed the small
      number of cases of TLS after treatment of nonhematologic malignancies reported
      between 1977 and 2002. After careful review of the literature, I describe what
      appears to be to the first reported case of TLS associated with chemotherapeutic
      treatment of metastatic prostate cancer.

PMID- 15148641
TI  - Pig-tailed macaques (Macaca nemestrina) possess six MHC-E families that are
      conserved among macaque species: implication for their binding to natural killer
      receptor variants.
AB  - MHC loci encode highly polymorphic molecules involved in the presentation of self
      and non-self peptides to cells of the adaptive and innate immune systems.
      Although variable, MHC-E genes are well conserved among primates and provide
      signals to natural killer cells. In this study, we sequenced and analyzed MHC-E
      alleles of pig-tailed macaque (Macaca nemestrina), a nonhuman primate used for
      HIV pathogenesis and vaccine studies. Among a group of seven macaques, the
      characterization of eight Mane-E alleles revealed an increased number of
      polymorphic sites compared with human HLA-E alleles. Phylogenetic analyses of MHC
      E alleles from pig-tailed macaque, rhesus monkey (Macaca mulatta) and cynomolgus
      macaque (Macaca fascicularis) demonstrated that the three macaque species shared
      six families of macaque MHC-E alleles and indicated that these families existed
      in the common ancestor 5.5 million years ago. Polymorphic Mane-E sites were not
      concentrated within the peptide-binding pockets, but were distributed throughout
      the entire ORF. The peptide-binding domain of Mane-E is similar to its human
      analogue, and peptide substrates theoretically capable of binding to Mane-E
      molecules were found in the leader sequence of classical Mane-A and -B molecules.
      Additionally, the polymorphic amino acids located in the alpha(1) and alpha(2)
      domains of Mane-E molecules have side chains expected to be oriented toward
      solvent and away from the peptide-binding groove, suggesting that some of them
      (positions 19, 73, 79 and 145) might be available for interaction with
      polymorphic receptors of natural killer cells.

PMID- 15148643
TI  - Perforated colon secondary to virtual colonoscopy: report of a case.
AB  - We describe a case of a perforated colon secondary to a virtual colonoscopy in an
      81-year-old female with ulcerative colitis. She underwent an emergent right
      hemicolectomy. The pathologic findings were described as ulcerative colitis with
      full-thickness perforation. To the best of our knowledge, this is the first
      complication from a virtual colonoscopy reported in the literature.

PMID- 15148642
TI  - Bioinformatic discovery and initial characterisation of nine novel antimicrobial
      peptide genes in the chicken.
AB  - Antimicrobial peptides (AMPs) are essential components of innate immunity in a
      range of species from Drosophila to humans and are generally thought to act by
      disrupting the membrane integrity of microbes. In order to discover novel AMPs in
      the chicken, we have implemented a bioinformatic approach that involves the
      clustering of more than 420,000 chicken expressed sequence tags (ESTs).
      Similarity searching of proteins-predicted to be encoded by these EST clusters
      for homology to known AMPs has resulted in the in silico identification of full
      length sequences for seven novel gallinacins (Gal-4 to Gal-10), a novel
      cathelicidin and a novel liver-expressed antimicrobial peptide 2 (LEAP-2) in the
      chicken. Differential gene expression of these novel genes has been demonstrated
      across a panel of chicken tissues. An evolutionary analysis of the gallinacin
      family has detected sites-primarily in the mature AMP-that are under positive
      selection in these molecules. The functional implications of these results are
      discussed.

PMID- 15148644
TI  - Hemophagocytic syndrome caused by fulminant ulcerative colitis and
      cytomegalovirus infection: report of a case.
AB  - We report a case of hemophagocytic syndrome that developed in a 35-year-old,
      Japanese male with fulminant ulcerative colitis. The patient underwent an
      emergency operation, consisting of subtotal colectomy, ileostomy with rectal
      preservation (suprapubic mucous fistula). After the operation, peripheral blood
      counts showed progressive pancytopenia and bone marrow aspirate smears revealed
      hypocellular bone marrow with an increase in histiocytes, indicating
      hemophagocytic syndrome. Viral studies (serum antibody titer and antigenemia of
      cytomegalovirus) revealed systemic cytomegalovirus infection. The patient was
      diagnosed with virus-associated hemophagocytic syndrome and was successfully
      treated with antiviral therapy consisting of intravenous ganciclovir, gamma
      globulin, and granulocyte-colony stimulating factor.

PMID- 15148646
TI  - Anterior levatorplasty for the treatment of chronic anal fissures in females with
      a rectocele: a randomized, controlled trial.
AB  - PURPOSE: It is postulated that an anterior anal fissure can result from mucosal
      trauma occurring during distention of a rectocele and that repair of the
      rectocele by anterior levatorplasty can lead to healing of these anal fissures.
      This study was designed to compare anterior levatorplasty with internal
      sphincterotomy for the management of anterior anal fissures in females with a
      rectocele. METHODS: From June 2000 until May 2002, 54 consecutive females with an
      anterior anal fissure and a rectocele were randomized to be managed by internal
      sphincterotomy or anterior levatorplasty. Preoperatively, manometry was
      performed, continence was measured using the Cleveland Clinic scoring system,
      pain scores were obtained using a visual analog scale, and the symptoms of
      bleeding and straining to defecate were assessed. Postoperatively, pain scores
      were obtained at Days 2, 7, and 21. Manometry, continence scores, and resolution
      of symptoms were measured between 8 and 12 weeks. Patient satisfaction and
      fissure healing also were assessed between 8 and 12 weeks. The average length of
      follow-up was 20 (range, 6-30) months. RESULTS: Postoperatively, lateral
      sphincterotomy caused a decrease in the resting pressures and anterior
      levatorplasty resulted in an increased length of the anal canal. Anterior
      levatorplasty also caused increased postoperative pain scores. There were no
      differences in fissure healing and patient satisfaction. CONCLUSIONS: These data
      suggest that anterior levatorplasty is an option for the management of patients
      with a rectocele, which may avoid the risk of incontinence with lateral internal
      sphincterotomy and better address the etiology of anterior anal fissures.

PMID- 15148645
TI  - Diverticulitis in young patients: is resection after a single attack always
      warranted?
AB  - PURPOSE: Diverticulitis has been described as a more virulent disease in young
      patients, necessitating an aggressive surgical approach. We hypothesized that the
      subgroup of young patients who do not require surgery on their initial
      presentation are unlikely to present at a later date with perforation and do not
      always require prophylactic resection as commonly recommended. METHODS: A
      retrospective chart review was conducted of all patients presenting to Fletcher
      Allen Health Care, the teaching hospital of the University of Vermont, from
      January 1, 1990 to June 30, 2001. Outcomes in patients aged 50 years or younger
      (Group 1) were compared with patients older than aged 50 years (Group 2) using a
      log-rank test. RESULTS: A total of 762 patients were admitted with sigmoid
      diverticulitis during the study period, 238 (31 percent) of whom underwent
      surgery. Two hundred fifty-nine patients (34 percent) were younger than aged 50
      years (Group 1). The risk of requiring surgery on initial hospital presentation
      was similar between the two groups (24 vs. 22 percent, respectively; P = 0.8).
      However, Group 1 patients were more likely to be treated operatively at some
      point during the study period (40 vs. 26 percent; P = 0.001) because of an
      increase in elective resections. Of 196 patients in Group 1 who had an initial
      medically managed admission, only 1 presented at a later date with perforation
      (0.5 percent). CONCLUSIONS: The risk of subsequent diverticular perforation in
      medically managed young patients with sigmoid diverticulitis is very low. As
      such, the frequently espoused policy of routine surgery after a single attack of
      diverticulitis in young patients may not be warranted. A more selective approach
      seems to be safe.

PMID- 15148647
TI  - Stapled hemorrhoidectomy with local anesthesia can be performed safely and cost
      efficiently.
AB  - PURPOSE: This prospective study was designed to assess the feasibility of
      performing the procedure for prolapsing hemorrhoids, or stapled hemorrhoidectomy,
      under local anesthesia supplemented with conscious sedation. METHODS: Seventy
      consecutive patients (mean age, 56 years; 37 males) with Grade 3 or 4 hemorrhoids
      underwent the procedure for prolapsing hemorrhoids after perianal infiltration of
      0.5 percent lidocaine with 1:200,000 epinephrine and supplemental conscious
      sedation. The procedure was performed in an outpatient setting, with the patient
      being discharged within two hours of checking into the ambulatory facility. All
      patients were assessed the following day by telephone, and then in the office at
      three weeks and two months for degree of postoperative pain, bleeding,
      continence, and time back to work or social activities. Additionally, all excised
      mucosal anastomotic rings were analyzed for presence or absence of muscle.
      RESULTS: Each patient rated the pain as minimal or none. Five patients complained
      of mild, transient perineal pressure, and three complained of fecal urgency and
      seepage before their first office visit; one complained of external skin tags at
      the second office visit. All subjects were back to work or social activities
      within three to four days-most within 48 hours. Complications included urinary
      retention in five patients, two of whom had a concomitant urinary tract
      infection, and one had urosepsis requiring hospitalization. One patient required
      immediate reoperation for bleeding from the staple line. Another patient was
      admitted for postoperative bleeding and packed with a hemostatic agent the
      evening of surgery. Muscularis propria fibers were identified in 68 of 70
      pathologic specimens. CONCLUSIONS: Administration of general, spinal, or epidural
      anesthesia for the procedure for prolapsing hemorrhoids is well described. This
      study suggests that the use of local anesthesia supplemented with conscious
      sedation for the procedure for prolapsing hemorrhoids yields results equivalent
      to those achieved with general or regional anesthesia without the attendant risks
      and additional costs. This study also suggests that the presence of muscle fibers
      in the pathologic specimen does not seem to lead to increased pain or impaired
      continence, although it was not specifically designed to address this issue.

PMID- 15148648
TI  - The direct closure of the internal fistula opening without advancement flap for
      transsphincteric fistulas-in-ano.
AB  - PURPOSE: The recommended closure techniques for transsphincteric fistulas
      demonstrate divergent results for postoperative continence and recurrence rates.
      An incontinence rate of 35 percent and a recurrence rate of up to 54 percent has
      been reported after transanal advancement techniques. The authors hypothesize
      that a direct closure of the internal fistula opening without tissue mobilization
      is easier to facilitate and generally leads to better clinical and functional
      results. METHODS: A prospective, observational study between 1995 and 1999 was
      undertaken in 90 patients with transsphincteric fistulas. A direct closure of the
      internal fistula opening without a flap was performed in all patients. A three
      layer, nonstaggered closure of mucosa, submucosa, internal, and external anal
      sphincters was performed. The follow-up time periods ranged from one-half to six
      (median, 2.6) years and included assessment of fistula recurrence and continence
      using patients' histories, physical examinations, proctoscopy, and continence
      scores. Statistical analysis was performed using Student's t-test or chi-squared
      test. RESULTS: Data from 90 patients with a total of 106 operations were analyzed
      (65 males and 41 females; average age 46 (range, 22-78) years). Sixty-six
      patients had previous anorectal abscess surgery, and 41 had a previous fistula
      operation. The mean number of previous fistula operations was 1.7. All patients
      were continent before surgery. Mean elapsed operative time period was 37 +/- 11
      minutes, and the mean anal retraction time was 20 +/- 7 minutes. Suture line
      dehiscence was the main postoperative complication. It was found to occur between
      the fourth and tenth postoperative days in 15 patients (14 percent). In 12 of 15
      patients (80 percent), the fistula persisted and operative treatment was
      necessary. In three patients (20 percent), spontaneous closure took place. A
      recurrent fistula after wound healing was observed in seven patients (6.6
      percent). The risk of developing a suture line dehiscence leading to a persistent
      fistula or a recurrent fistula was 22.5 percent. Ninety-four percent of the
      patients were continent (continence score 0), 6 percent had a minimal disorder of
      continence (score 4). A continence level for all patients was determined by the
      international classification of continence disorders. CONCLUSIONS: Direct closure
      for the treatment of transsphincteric fistulas is a safe and effective approach
      and achieves a good functional outcome; a small risk of suture line dehiscence,
      which may lead to a recurrent or persistent fistula, remains.

PMID- 15148649
TI  - Deleted in colorectal cancer protein expression as a possible predictor of
      response to adjuvant chemotherapy in colorectal cancer patients.
AB  - PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for
      patients with colorectal carcinoma. This study was designed to investigate
      whether the expression of the DCC protein also can predict response to adjuvant
      chemotherapy. METHODS: The expression of DCC was evaluated immunohistochemically
      in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and
      Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median,
      64) months. Follow-up was at least five years for all patients who are alive. End
      points of the study were recurrence of disease and death. Forty-eight patients
      received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated.
      RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive
      (DCC+). Proportion of survival and disease-free survival were higher in the DCC+
      patients (83 percent) than in deleted in colorectal cancer-negative (DCC-; 54
      percent). In the DCC+ group, adjuvant treatment was a strong positive predictive
      factor for survival and disease-free survival. All DCC+ patients who received
      adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas
      without chemotherapy (CHEMO-) only 54 percent are alive ( P = 0.0001). When
      stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+
      had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO-
      survival rate was 75 percent and disease-free survival rate 62 percent ( P =
      0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free
      survival of 100 percent, whereas in DCC+/CHEMO- both dropped to zero ( P =
      0.0002). On the other hand, in the DCC- tumors, there was no statistical
      significant relationship between chemotherapy and survival or disease-free
      survival (DCC-/CHEMO- had 57 percent survival; DCC-/CHEMO+ had 52 percent
      survival). CONCLUSIONS: DCC is a prognostic factor for colorectal cancer.
      Positive expression of DCC identifies a subgroup of patients who respond
      favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent
      survival and disease-free survival rates. Without treatment, the survival rate of
      DCC+ patients dropped significantly. We suggest that DCC immunostaining should be
      performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For
      DCC- tumors, a larger cohort of patients should be studied before definitive
      conclusions can be drawn; however, clinical trials of new drug combinations
      should focus on DCC- patients.

PMID- 15148650
TI  - Actual colonic perforation in virtual colonoscopy: report of a case.
AB  - Computed tomography colonography, also termed virtual colonoscopy, is a new
      imaging method to investigate the colon, which may be a potential alternative to
      the conventional endoscopic colonoscopy in some cases. The high safety profile of
      this imaging method was considered as an additional advantage of this procedure.
      A case of colonic perforation in computed tomography colonography is presented,
      highlighting a potential risk related to this procedure. It is assumed that
      perforation was the result of overinflation of air into an obstructed colon
      caused by a lesion at the rectosigmoid junction. Thus, it is suggested that in
      such cases, air insufflation should be gradual, thereby minimizing the risk of
      perforation.

PMID- 15148651
TI  - Multichannel place pitch sensitivity in cochlear implant recipients.
AB  - Cochlear implant recipients perceive a rise in pitch when the site of stimulation
      is moved from the apex toward the base. The place pitch sensitivity is typically
      measured using the stimulation of single channels. However, all current cochlear
      implant devices stimulate multiple channels simultaneously or with pulses
      temporally interleaved. The primary goal of the present study is to test whether
      the sensitivity of a cochlear implant recipient to changes in perceived pitch
      associated with changes of place of excitation improves or deteriorates when the
      number of active channels is increased, compared with stimulation with only one
      active channel. Place pitch sensitivity was recorded in four Nucleus CI24
      subjects as a function of number of active channels (from 1 to 8). Just
      noticeable differences were estimated from a constant stimuli 2AFC pitch-ranking
      experiment with roving loudness. Reference and comparison stimuli contained the
      same number of active channels but were shifted one or two electrodes toward the
      base or toward the apex. The place pitch sensitivity was measured using monopolar
      stimulation at two locations along the electrode array. To minimize cues related
      to loudness, the multichannel stimuli were loudness balanced relative to the
      single-channel stimuli presented at C-level. The number of active channels did
      not affect place pitch sensitivity. This is consistent with a model that compares
      the edges of the excitation pattern irrespective of the overlap between
      excitation patterns. There was a significant difference in sensitivity to place
      pitch among subjects. The average just noticeable differences of place pitch,
      extrapolated from a fitting procedure, for the subjects ranged from 0.25 mm to
      0.46 mm.

PMID- 15148652
TI  - Demographics and prevalent risk factors of chronic subdural haematoma: results of
      a large single-center cohort study.
AB  - Chronic subdural haematoma (CSDH) is a typical disease in elderly patients and
      encountered frequently in neurosurgical practice. With an increasing number of
      elderly people in the general population, there is a need to investigate risk
      factors (age, falls, anticoagulant or antithrombotic therapy) which could be
      pertinent to the development of this disease. We reviewed 354 patients undergoing
      surgery for CSDH over a period of 7 years (1996-2002), the occurrence being
      equally distributed over these years. CSDH occurred more often in elderly (> or =
      65 years) than in younger people (69 vs 31%), and in men than in women (64 vs
      36%). Falls were reported in 77% of patients. There was a trend towards a higher
      risk of falls in the elderly. Antithrombotic or anticoagulant therapy was present
      in 41% of patients, 32% of them having had falls. Overall postoperative mortality
      was 0% and overall recurrence rate 13.6%. CSDH in the elderly population,
      especially in men, is frequently associated with falls and anticoagulation or
      antithrombotic therapy. The indication for these medications, especially in
      elderly patients at risk for falls, should be carefully evaluated and controlled.

PMID- 15148653
TI  - Epidemiology of rubella infections in Austria: important lessons to be learned.
AB  - In order to ascertain the epidemiology of rubella infections in Austria, a
      seroepidemiological study was performed. Data collected from 115 cases diagnosed
      at the Institute of Hygiene and Social Medicine of the University of Innsbruck
      during 2001 were evaluated. The results indicate this infection can no longer be
      categorised as a paediatric disease (mean age, 18.5 years), and several other
      findings were particularly striking: (i) 47% of the patients had elevated C
      reactive protein levels and 50% had increased anti-streptolysin O titres; (ii)
      only a few patients complained of fever, while symptoms such as rash and
      lymphadenopathy, which are also associated with several other viral infections,
      including HIV, were found frequently; and (iii) the 115 rubella cases detected in
      the 1-year study period represented an incidence of >13 per 100,000 population.
      This high incidence of infection underlines the need for further improvement of
      diagnostic tests and more successful vaccine strategies.

PMID- 15148654
TI  - Factors associated with antimicrobial resistance among clinical isolates of
      Klebsiella pneumoniae: 1-year survey in a French university hospital.
AB  - Klebsiella pneumoniae is an opportunistic pathogen responsible for nosocomial
      infections. Both resistance to multiple antibiotics and the expression of
      virulence factors are likely to be involved in the physiopathological process. In
      this study, 227 isolates of K. pneumoniae collected over a 1-year period in a
      teaching hospital in Clermont-Ferrand, France, were investigated for their
      antibiotic resistance pattern and the presence of several potential virulence
      traits. Enterobacterial repetitive intergenic consensus polymerase chain reaction
      (ERIC-PCR) indicated that most of the isolates were phylogenetically unrelated.
      When tested in an in vitro adhesion assay with Int-407 intestinal cells, the
      median adhesion index was 5.5x10(4) bacteria/cm(2) (range, 2.0x10(2)-3.4x10(5)).
      Isolates resistant to cefoxitin, chloramphenicol, and quinolones showed
      significantly lower adhesion indexes. The frequency of mutagenesis conferring
      resistance to rifampicin was low for most of the isolates. The median mutagenesis
      frequency was 1.0x10(-8) (range, 2.5x10(-9)-3.2x10(-6)) at 24 h and 1.1x10(-8)
      (range, 1.8x10(-9)-1.2x10(-5)) at 7 days. In contrast, isolates resistant to
      cefoxitin, chloramphenicol, and tetracycline showed a significantly greater
      ability to mutate. These results suggest a link between adhesion capabilities and
      resistance to certain antibiotics. They furthermore indicate that strains with a
      high mutagenesis capacity are more likely to acquire antibiotic resistance genes.
      The high pathogenicity island of Yersinia was detected in 16.3% of the strains
      and was more often associated with isolates resistant to nalidixic acid and
      augmentin.

PMID- 15148656
TI  - Identification and functional analysis of a defect in the human ALG9 gene:
      definition of congenital disorder of glycosylation type IL.
AB  - Defects of lipid-linked oligosaccharide assembly lead to alterations of N-linked
      glycosylation known as "type I congenital disorders of glycosylation" (CDG).
      Dysfunctions along this stepwise assembly pathway are characterized by
      intracellular accumulation of intermediate lipid-linked oligosaccharides, the
      detection of which contributes to the identification of underlying enzymatic
      defects. Using this approach, we have found, in a patient with CDG, a deficiency
      of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of
      lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was
      paralleled by the transfer of incomplete oligosaccharides precursors to protein.
      A homozygous point-mutation 1567G-->A (amino acid substitution E523K) was
      detected in the ALG9 gene. The functional homology between the human ALG9 and
      Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K
      mutation detected in the patient with CDG, were confirmed by a yeast
      complementation assay lacking the ALG9 gene. The ALG9 defect found in the patient
      with CDG--who presented with developmental delay, hypotonia, seizures, and
      hepatomegaly--shows that efficient lipid-linked oligosaccharide synthesis is
      required for proper human development and physiology. The ALG9 defect presented
      here defines a novel form of CDG named "CDG-IL."

PMID- 15148659
TI  - Abstracts of the 8th International Congress of Parkinson's Disease and Movement
      Disorders. June 14-17, 2004. Rome, Italy.

PMID- 15148657
TI  - Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when
      alternate low-copy repeats act as homologous recombination substrates.
AB  - Several homologous recombination "hotspots," or sites of positional preference
      for strand exchanges, associated with recurrent deletions and duplications have
      been reported within large low-copy repeats (LCRs). Recently, such a hotspot was
      identified in patients with the Smith-Magenis syndrome (SMS) common deletion of
      approximately 4 Mb or a reciprocal duplication within the KER gene cluster of the
      SMS-REP LCRs, in which 50% of analyzed strand exchanges resulting in deletion and
      23% of those resulting in duplication occurred. Here, we report an additional
      recombination hotspot within LCR17pA and LCR17pD, which serve as alternative
      substrates for nonallelic homologous recombination that results in large
      (approximately 5 Mb) deletions of 17p11.2, which include the SMS region. Using
      polymerase-chain-reaction mapping of somatic cell hybrid lines, we refined the
      breakpoints of six deletions within these LCRs. Sequence analysis of the
      recombinant junctions revealed that all six strand exchanges occurred within a
      524-bp interval, and four of them occurred within an AluSq/x element. This
      interval represents only 0.5% of the 124-kb stretch of 98.6% sequence identity
      between LCR17pA and LCR17pD. A search for potentially stimulating sequence motifs
      revealed short AT-rich segments flanking the recombination hotspot. Our findings
      indicate that alternative LCRs can mediate rearrangements, resulting in
      haploinsufficiency of the SMS critical region, and reimplicate homologous
      recombination as a major mechanism for genomic disorders.

PMID- 15148655
TI  - Dengue: an arthropod-borne disease of global importance.
AB  - Dengue viruses cause a variable spectrum of disease that ranges from an
      undifferentiated fever to dengue fever to the potentially fatal dengue shock
      syndrome. Due to the increased incidence and geographical distribution of dengue
      in the last 50 years, dengue is becoming increasingly recognised as one of the
      world's major infectious diseases. This article will review clinical and
      diagnostic aspects of dengue virus infections. It also presents our current
      knowledge of the pathophysiology of severe dengue and addresses the importance of
      dengue virus infections in those travelling to parts of the world where dengue is
      endemic.

PMID- 15148658
TI  - Linkage disequilibrium mapping via cladistic analysis of single-nucleotide
      polymorphism haplotypes.
AB  - We present a novel approach to disease-gene mapping via cladistic analysis of
      single-nucleotide polymorphism (SNP) haplotypes obtained from large-scale,
      population-based association studies, applicable to whole-genome screens,
      candidate-gene studies, or fine-scale mapping. Clades of haplotypes are tested
      for association with disease, exploiting the expected similarity of chromosomes
      with recent shared ancestry in the region flanking the disease gene. The method
      is developed in a logistic-regression framework and can easily incorporate
      covariates such as environmental risk factors or additional unlinked loci to
      allow for population structure. To evaluate the power of this approach to detect
      disease-marker association, we have developed a simulation algorithm to generate
      high-density SNP data with short-range linkage disequilibrium based on empirical
      patterns of haplotype diversity. The results of the simulation study highlight
      substantial gains in power over single-locus tests for a wide range of disease
      models, despite overcorrection for multiple testing.

PMID- 15148681
TI  - Abstracts of the 27th Annual Meeting of the American Society of Primatologists.
      June 8-11, 2004, Madison, Wisconsin, USA.

PMID- 15148683
TI  - Beta2-amino acids-syntheses, occurrence in natural products, and components of
      beta-peptides1,2.
AB  - Although they are less abundant than their alpha-analogues, beta-amino acids
      occur in nature both in free form and bound to peptides. Oligomers composed
      exclusively of beta-amino acids (so-called beta-peptides) might be the most
      thoroughly investigated peptidomimetics. Beside the facts that they are stable to
      metabolism, exhibit slow microbial degradation, and are inherently stable to
      proteases and peptidases, they fold into well-ordered secondary structures
      consisting of helices, turns, and sheets. In this respect, the most intriguing
      effects have been observed when beta2-amino acids are present in the beta-peptide
      backbone. This review gives an overview of the occurrence and importance of beta2
      amino acids in nature, placing emphasis on the metabolic pathways of beta
      aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as
      secondary metabolites or as components of more complex natural products, such as
      peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of
      the syntheses of both achiral and chiral beta2-amino acids is presented. While
      there are numerous routes to achiral beta2-amino acids, their EPC synthesis is
      currently the subject of many investigations. These include the
      diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic
      beta-homoglycine derivatives containing chiral auxiliaries, the Curtius
      degradation, the employment of transition-metal catalyzed reactions such as
      enantioselective hydrogenations, reductions, C-H insertions, and Michael-type
      additions, and the resolution of rac. beta2-amino acids, as well as several
      miscellaneous methods. In the last part of the review, the importance of beta2
      amino acids in the formation of beta-peptide secondary structures is discussed.

PMID- 15148684
TI  - Identification of stable helical bundles from a combinatorial library of
      amphipathic peptides.
AB  - A set of combinatorial amphipathic helical peptides referred to as the KIA series
      has been screened to identify native-like helical bundles. The series contains
      the following consensus sequence: AKAxAAxxKAxAAxxKAGGY, where "x" positions are
      occupied by either Ala or Ile. The peptide sequences in the series comprise all
      possible combinations of four Ile residues occupying the six x positions. In each
      case, Ala occupied the two x positions not occupied by Ile. There are a total of
      15 peptides in the KIA series; all of the peptides differ in the number of ridges
      and grooves formed by the Ile side chains, and two of the KIA peptides possess a
      canonical knobs-into-holes heptad repeat. The structure and stability of these 15
      peptides and their pairwise mixtures were evaluated. One peptide in the series
      formed a stable four-helix bundle that folded with cooperativity similar to
      native proteins. Ten peptides assembled into molten globular helical assemblies,
      two peptides were unstructured, and two peptides assembled into helical filaments
      that were several micrometers long. One of the helical filament forming peptides
      could be diverted from forming filaments by the addition of another KIA peptide,
      and resulted in the formation of a heteromeric six-helix bundle. This study
      demonstrates that combinatorial peptides composed of only three types of amino
      acids can form a diverse array of structures, some of which are native-like.

PMID- 15148685
TI  - The biological potency of a series of analogues of human calcitonin correlates
      with their interactions with phospholipids.
AB  - The conformational and lipid binding properties of several calcitonin analogs
      were compared. These analogs were designed to have the central amphipathic
      helical region of salmon calcitonin and N- and C-terminal segments similar to
      human calcitonin. The various analogs differed from one another either by removal
      of Leu19 from this hybrid analog, replacement of Leu19 with Gly19 or having a
      carboxyl terminus more closely related to salmon calcitonin. It had been found
      that replacement of Leu19 with Gly19 caused a marked reduction in the hypocalemic
      activity of the analog. The ability of the analogs to form helical structures in
      the presence of dimyristoylphosphatidylglycerol as well as their ability to lower
      the enthalpy of the calorimetric phase transition of this phospholipid correlates
      well with the hypocalcemic potency of the peptide.

PMID- 15148686
TI  - Structural characterization of VGVAPG, an elastin-derived peptide.
AB  - Elastic fibers are an important component of the extracellular matrix, providing
      elasticity and resilience to tissues that require the ability to deform
      repetitively and reversibly. Among the elastin-derived peptides, the Val-Gly-Val
      Ala-Pro-Gly (VGVAPG) hexapeptide is known for its chemotactic activity and
      metalloproteinases upregulation properties. As other elastin-derived peptides,
      having homologous similar sequences, do not exhibit any biological activity, the
      following question arises: Does the peptide-receptor interaction need a specific
      active conformation? Previous experimental studies including NMR and CD
      spectroscopies did not clearly identify the conformations adopted by the VGVAPG
      peptide in solution. However, structural predictions made on VGVAPG and related
      XGXXPG peptides suggested a folded beta-turn conformation. So we undertook a
      theoretical and experimental study of the VGVAPG peptide. The work presented
      here, which gives an overall structural description of VGVAPG behavior in water,
      also provides an additional insight into its structure-activity relationship.
      Both theoretical and experimental results suggest the existence of an ensemble of
      rather extended and folded conformations in solution. All the folded structures
      obtained exhibit a type VIII beta-turn spanning the GVAP sequence. In the lack of
      any structural information concerning the elastin receptor, these results suggest
      that such a conformation could be relevant for the peptide-receptor interaction
      and thus for biological activity.

PMID- 15148687
TI  - Gender differences in pain experience and pain management.

PMID- 15148688
TI  - Risk factors associated with postoperative sore throat after tracheal intubation:
      an evaluation in the postanesthetic recovery room.
AB  - BACKGROUND: Postoperative sore throat after tracheal intubation is an unpleasant
      and distressing experience to patients. The aim of the study was to carry out a
      large-scale search for the risk factors of postoperative sore throat in patients
      undergoing endotracheal general anesthesia. METHODS: During a 6-month study
      period, patients (> or = 10 years old) who consecutively underwent endotracheal
      general anesthesia for all kinds of surgical procedures were included. A total of
      7541 patients were recruited in our study. RESULTS: Five risk factors associated
      with postoperative sore throat were identified. They were female gender, age
      between 30-39, surgical sites within the oral or nasal cavity, or around the
      neck, use of nitrous oxide during anesthesia, and duration of anesthesia longer
      than 2 hours. CONCLUSIONS: Five risk factors related to postoperative sore throat
      were identified in our study.

PMID- 15148689
TI  - Attitudes of the patients and their families towards cancellation of anesthesia
      and surgery in hypertensive patients.
AB  - BACKGROUND: Pre-operative hypertension which is a common cause for cancellation
      of scheduled surgery is not merely a medical consideration. Understanding the
      patients' and their families' attitudes towards this issue may help develop an
      efficient system of qualitative management and promote the utilization of medical
      resources in a hospital. METHODS: Questionnaire of the study regarding the
      attitudes towards pre-operative hypertension and cancellation of scheduled
      surgery was answered through interviews by the patients and families admitted in
      a rural hospital in early 2003. RESULTS: A total of 189 people were interviewed.
      Over 42% of interviewees said that cancellation of scheduled surgery in
      hypertensive patients was acceptable. Nearly 43% felt that such a cancellation
      did not cause any loss to patient. However, less than 12% of respondents could
      accept the occurrence of a post-operative cardiovascular complication as a
      reasonable event even though most of them acknowledged that a hypertensive
      patient was not a good risk for surgery. If any loss or complication occurred,
      more than half of them thought that it was the surgeon's fault. CONCLUSIONS: Most
      patients and families in this rural area accept case cancellation rather than
      tempt the suffering of a post-operative cardiovascular complication. Developing a
      standard guideline for postponement of anesthesia and surgery in hypertensive
      patients may help reduce the variability in practising and management, with
      resultant increase of operating suite efficiency.

PMID- 15148690
TI  - Gender differences in pain perception: a signal detection theory approach.
AB  - BACKGROUND: Overseas studies suggest women report more pain and are more
      vulnerable to chronic pain conditions compared with men, however, it is unclear
      whether this difference in pain perception is due to sensory or non-sensory
      factors such as anxiety. Since gender differences in pain perception may have
      important implications for pain management, it is crucial that the relationship
      between pain, gender and anxiety in this culture be clarified. METHODS: The
      Signal Detection Theory Approach was used to determine gender differences in
      sensory discrimination [P(A)] and response bias (B). One hundred and twenty six
      Hong Kong Chinese adults responded to thirty pairs of thermal stimuli (36 degrees
      C-48 degrees C) and their responses to these stimuli were analyzed by computer
      software. The adapted Chinese version of the State-Trait Anxiety Inventory (STAI
      Y) was used to assess state and trait anxiety of participants. RESULTS: Compared
      with men, women showed enhanced sensory discriminability (P = 0.004) and were
      less stoical in their response to pain (P = 0.03). Although there was no
      significant gender difference in state and trait anxiety, sensory discrimination
      was positively correlated with state anxiety (r = 0.19) and response bias was
      negatively correlated with trait anxiety (r = -0.18). The content validity index
      for the STAI-Y was 0.9 and the co-efficient alpha for reliability for state and
      trait anxiety was 0.88 and 0.92, respectively. CONCLUSIONS: Enhanced sensory
      discriminability in women may explain why women report more pain and seek
      healthcare more frequently compared with men. Men showed more stoical response to
      pain possibly because of gender-role expectations. The Signal Detection Theory
      approach was instrumental in assessing the sensory and non-sensory dimensions of
      pain perception. Awareness of the effects of gender and anxiety in pain
      perception will enable clinicians to be more efficient pain managers.

PMID- 15148691
TI  - Change in expression of the guanosine triphosphate cyclohydrolase I in LPS
      stimulated rats is tissue specific.
AB  - BACKGROUND: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for
      inducible nitric oxide synthase (iNOS), has been reported to be controlled by
      guanosine triphosphate cyclohydrolase I (GTPCH). Previous studies have
      demonstrated that GTPCH was induced by bacterial toxin. However, in a study using
      lipopolysaccharide (LPS)-treated murine macrophages model, we found that GTPCH
      expression was in fact constitutive rather than inducible. To further elucidate
      the effects of endotoxemia on GTPCH expression, we therefore preformed this LPS
      treated rodent endotoxemia study with special focus on lung, liver, and kidney.
      METHODS: Rats randomly received either normal saline (N/S) or LPS injection. At
      five different time points (0, 1, 2, 3 and 4 h after LPS injection in LPS group
      and comparable time points in N/S group), four rats from each group were
      sacrificed. Snap frozen tissues were then analyzed using semi-quantitative RT-PCR
      to determine GTPCH mRNA concentrations. RESULTS: GTPCH mRNA concentrations in
      lung and liver tissues were similar between groups. On the other hand, GTPCH mRNA
      concentrations in renal tissues were significantly higher in the LPS group as
      compared with the N/S group. Our data demonstrated that GTPCH expression in lung
      and liver tissues was constitutive rather than inducible, whereas renal GTPCH
      expression was induced by LPS in a time-dependent manner. CONCLUSIONS: GTPCH
      expression is tissue specific. Different tissues react differently to endotoxemia
      in terms of GTPCH expression. Therefore, efforts aiming at modulating GTPCH
      expression to limit NO overproduction should adjust accordingly.

PMID- 15148692
TI  - Confocal laser scanning microscopy: I. An overview of principle and practice in
      biomedical research.
AB  - Evolving from conventional microscopic technologies, confocal microscopy has
      proved itself to play an important role in the biomedical research during the
      past decade. Confocal microscope has many advantages over traditional microscope
      including the ability to look deeply into inside cells with less photodamage and
      photobleach, reconstruct three-dimensional images, and chart intracellular
      dynamic events in the living cells. With these remarkable properties and the
      availability of fluorescent dyes for living cells, the confocal microscopy has
      been widely used in solving many unknown questions in biological and
      pharmacological fields. In clinics, confocal microscope has also served as an
      important tool to observe the living cells in skins and eyes. For
      anesthesiologists, confocal microscope has made possible novel experimental
      approaches for the effects of multiple anesthetic agents on cells. Furthermore,
      the technology of fibreoptical confocal endomicroscopy is now on its way of
      maturation. It will soon be the era for confocal microscopy to explore the "cell
      behavior" inside of intact living tissues.

PMID- 15148693
TI  - Application of wire-guided endobronchial blocker for one-lung ventilation in
      patient with tracheostomy--a case report.
AB  - One-lung ventilation (OLV) with a double-lumen endotracheal tube or Univent may
      be achieved difficulty in morbidly obese, mouth opening-limited or critically ill
      patients. Now, a new fiberoptically directed wire-guided endobronchial blocker
      (WEB) can be applied for these conditions. We report the use of a new
      endobronchial blocker in a pharyngeal cancer patient after pharyngectomy. The
      original 10# Shiley endotracheal tube was exchanged with reinforced cuffed
      tracheal tube. Then we use the WEB to achieve OLV. The WEB was guided by a loop,
      and through the appropriate position of left main bronchus by pediatric
      fiberoptic bronchoscope. Finally, OLV was accomplished smoothly with combination
      of a non-kinking endotracheal tube and a WEB.

PMID- 15148694
TI  - Cardiac catheterization-induced type-A aortic dissection detected by intra
      operative transesophageal echocardiography--a case report.
AB  - Cardiac catheterization is not only a diagnostic tool but also a means of
      treatment of coronary artery disease. Coronary artery dissection is one of the
      complications of cardiac catheterization. Emergency coronary artery bypass graft
      (CABG) surgery is indicated when coronary artery dissection is associated with
      unstable perfusion or residual severe stenosis. We present a case of progressive
      type-A aortic dissection as a continuity of catheterization-induced dissection of
      right coronary artery (RCA) with occlusion, disclosed by transesophageal
      echocardiography (TEE) during the emergent CABG surgery for the iatrogenic
      injury. Once the aortic dissection has been diagnosed by TEE, the surgical
      procedure and cannulation site for cardiopulmonary bypass were altered from those
      used in regular CABG surgery. Therefore, TEE is able and valuable in such
      situation to detect this rare but severe complication due to catheterization,
      especially when retrograde coronary artery dissection has been noted
      preoperatively.

PMID- 15148696
TI  - An accidental intra-arterial injection of thiopental on the dorsum of the foot--a
      case report.
AB  - Since its maiden clinical use decades back, innumerable instances of accidental
      intra-arterial injection of the drug have been reported mostly in the upper
      extremities. We report an accidental intra-arterial injection of thiopental into
      one of the tributaries of the arterial arch of the dorsum of the foot, but timely
      and prompt treatment with lidocaine and heparin together with leg rising
      prevented a gangrenous episode of the extremity and resulted in an uneventful
      recovery. This report emphasizes the importance of extreme caution while
      cannulating the veins on the dorsum of the foot. Attention should be focused on
      the patient's reactions, the feeling of an intense pain and withdrawal of the leg
      during injection so that timely therapeutic measures are undertaken and the sad
      episode is prevented.

PMID- 15148695
TI  - Pulmonary alveolar proteinosis undergoing whole lung lavage in south Taiwan--a
      case report.
AB  - Pulmonary alveolar proteinosis (PAP) is rarely seen in Taiwan. According to the
      literature the incidence is one in two million with a male to female ratio of 3
      to 1. The pathohistology of PAP is associated with the filling of the alveoli by
      a proteinaceous material. PAP can be divided into primary and secondary forms.
      PAP was once diagnosed by open lung biopsy, but since the introduction of
      bronchoalveolar lavage, open lung biopsy is less common now for the diagnosis of
      PAP. The most definite and effective therapy for PAP is whole lung lavage (WLL).
      Therapeutic WLL is performed under one-lung general anesthesia with a double
      lumen tube (DLT). This procedure is associated with three problems: 1. hypoxia.
      2. circulatory disturbance. 3. difficulty in positioning the DLT. We present a
      case undergoing WLL in our hospital who had contracted pulmonary TB was diagnosed
      as a case of PAP by open lung biopsy. She was convinced to receive WLL because of
      intolerance of daily activity. The result of the left lung lavage was excellent,
      but the attempt on the other lung at a later time was cancelled because of
      difficulty in positioning the DLT due to tracheal stenosis. Here we would like to
      give an account of our management and discuss about PAP and WLL after literature
      review.

PMID- 15148697
TI  - Collective thinking.

PMID- 15148698
TI  - Managing the juggling act.

PMID- 15148699
TI  - Making every vote count.

PMID- 15148700
TI  - Florence Nightingale: still lighting the way for nurses.

PMID- 15148701
TI  - Valuing your skills.

PMID- 15148702
TI  - The future of education.

PMID- 15148703
TI  - All work and low pay.

PMID- 15148704
TI  - 'Racialisation' and racism.

PMID- 15148705
TI  - Elective admissions.

PMID- 15148706
TI  - Clinical management where medicine meets management. Frail safe.
AB  - Hospitals need to strive to reduce admissions and improve quality of care for
      frail older people. Dedicated units within accident and emergency offer the best
      hope of reducing demeaning trolley waits. Community-based care and home treatment
      needs to be better co-ordinated to reduce the burden on hospitals.

PMID- 15148707
TI  - Health inequalities. Measure for measure.
AB  - National guides for assessing inequality at local level are inconsistent. A
      simple tool, the slope index of inequality, measures inequalities in health
      across the whole population of a primary care trust. The Index enables PCTs to
      measure inequality by health outcome and service provision.

PMID- 15148708
TI  - Law. Don't look now.

PMID- 15148709
TI  - Mental health. Key concerns.

PMID- 15148710
TI  - My brilliant career--human resources. Style counsel. Interview by Carol Lewis.

PMID- 15148711
TI  - HSJ people. Into extra time.

PMID- 15148712
TI  - Buildings. Pull a fast one.

PMID- 15148713
TI  - Buildings. Second bite at the cherry.

PMID- 15148715
TI  - Buildings. One vision.

PMID- 15148714
TI  - Buildings. Market forces.

PMID- 15148716
TI  - Perspective. Easy fix for high drug costs? Guess again, America.

PMID- 15148717
TI  - [More and more researchers are tempted to cheat. Tougher competition concerning
      resource allocation and career possibilities].

PMID- 15148718
TI  - [Focus on proton pump inhibitors. The phenomenon of (over)compensation is not odd
      but normal].

PMID- 15148720
TI  - [Proton pumps inhibitors can create chronic needs].

PMID- 15148719
TI  - [GIST--a significantly more common tumor than earlier apprehended. New
      discoveries on the pathogenesis of GIST yielded new medical treatment].

PMID- 15148721
TI  - [Analysis of beta-"trace" protein detects leakage of cerebrospinal fluid.
      Quickly, safely and cheaply].
AB  - beta-trace protein is an immunological marker for the detection of cerebrospinal
      fluid leakage to the nose or ear. Analysis of beta-trace protein via a
      nephelometric assay is a valuable test for the identification of cerebrospinal
      fluid in rhinorrhea or otorrhea.

PMID- 15148722
TI  - [Changes in health care organization should have scientific basis].

PMID- 15148723
TI  - [The "to be or not to be" of the scientific congresses. Reduced resources and
      virtual meetings hit against pleasure-trips].

PMID- 15148724
TI  - [Melancholia--disease or godsent gift?].

PMID- 15148725
TI  - [Global health care still needs the WHO--in spite of the World Bank and Bill
      Gates].

PMID- 15148726
TI  - [The ADHD-DAMP debate. The scientific community must protect the reliance in
      scientific authority].

PMID- 15148727
TI  - [The coxiber debate--but what about paracetamol?].

PMID- 15148728
TI  - [Professional ethics of the Medical Society can not be modified haphazardly].

PMID- 15148730
TI  - [The "gender perspective" as a last attempt].

PMID- 15148731
TI  - [Print the indication on the tablet container].

PMID- 15148732
TI  - [Statins increase the risk of cancer among the elderly].

PMID- 15148733
TI  - [Recent changes in glaucoma management].

PMID- 15148734
TI  - [Significance of leukocytes in the regulation of retinal edema, ischemia, and
      angiogenesis].
AB  - BACKGROUND: Involvement of leukocytes in three major pathologic conditions in the
      retina, i.e., edema, ischemia, and angiogenesis, has recently been thoroughly
      investigated. The accumulated evidence will lead to an integrated understanding
      of the relationship between leukocytes and retinal disorders, which is required
      for clinical applications of new medical treatment. METHOD: Leukocyte roles in
      the retinal vascular pathology were assessed by reviewing the related literature.
      RESULTS: Vascular endothelial growth factor(VEGF)-induced leukocyte adhesion to
      the retinal vessels was shown to result in blood-retinal barrier breakdown, and
      the leukocyte-mediated pathogenesis was also seen in a model of diabetic
      retinopathy. A possible mechanism by which retinal angiogenesis develops
      intraviteral proliferation instead of compensating the avascular retina is that
      VEGF-producing monocytes/macrophages infiltrate the vitreous with subsequent
      migration of retinal vascular endothelial cells. On the other hand, cytotoxic T
      lymphocyte-mediated apoptosis of endothelial cells appears to cause the
      suppression of pathological retinal angiogenesis and the formation of ischemic
      retina secondary to vascular regression. CONCLUSION: Leukocytes are considered to
      regulate retinal edema, ischemia, and angiogenesis.

PMID- 15148735
TI  - [Low vision aids for reading in scar stage of age-related macular degeneration].
AB  - PURPOSE: To evaluate the inter-relationship among near visual acuity,
      eccentricity of preferred retinal locus(PRL), and choice of low vision aids for
      reading in patients with bilateral age-related macular degeneration(AMD).
      SUBJECTS AND METHODS: The preferred eye of 44 patients having bilateral disciform
      stage AMD was examined. The PRL was detected and its eccentricity from the fovea
      was measured by scanning laser ophthalmoscopic microperimetry. Magnification of a
      low vision aid for reading newsprint was determined by the critical print size
      which was calculated using the MNREAD-J. The type of preferred aid was chosen
      from high-plus lens glasses, magnifiers, and closed-circuit televisions. The
      inter-relationship among near visual acuity, eccentricity of the PRL, and
      magnification and type of low vision aid for reading were evaluated. RESULTS: The
      magnification of the aid was correlated with the eccentricity of PRL in eyes with
      near visual acuity of 0.2 or less although no correlation was found in eyes with
      near visual acuity better than 0.3. High plus lens glasses were selected by
      patients with near visual acuity better than 0.2 and eccentricity of 2 degrees or
      less. Magnifiers were selected by patients with near visual acuity better than
      0.1 and eccentricity of 5 degrees or less. Closed-circuit televisions were
      selected by patients with near visual acuity of 0.1 or less and eccentricity of 5
      degrees or more. CONCLUSION: The eccentricity of PRL should be taken into account
      in determining low vision aids for reading, especially in patients with near
      visual acuity of 0.2 or less. Choice of the type of low vision aid depends on not
      only near visual acuity but also on eccentricity of PRL.

PMID- 15148737
TI  - [Analysis of retinal nerve fiber layer thickness measured by optical coherence
      tomography in glaucomatous eyes with hemifield defect].
AB  - PURPOSE: To analyze the retinal nerve fiber layer thickness(NFLT) as measured by
      optical coherence tomography(OCT) in glaucomatous eyes with hemifield defect and
      to evaluate the most effective parameter for the diagnosis of glaucoma with OCT.
      METHODS: One hundred eighty four(184) normal eyes(128 subjects) and 108 open
      angle glaucomatous eyes(87 subjects) with superior or inferior hemifield defects
      verified by Humphrey field analyzer(HFA) were measured for NFLT with OCT. The
      correlations between NFLT and mean deviation on HFA were calculated. In
      combination with normal eye data, receiver operating characteristic curve(ROC
      curve) and AUC(area under the curve) of each NFLT in the affected hemifield were
      evaluated for the diagnosis of glaucoma. RESULTS: NFLT in both affected and
      unaffected hemifields was significantly correlated with mean deviation in HFA. An
      average of four 30 degrees segments close to the temporal side in the affected
      hemifield (parameter A120) had the highest correlation(r = 0.571) and the highest
      AUC(0.948) among all parameters. CONCLUSIONS: NFLT in the unaffected visual field
      decreases with the progression of glaucomatous damage. We suggest that the
      parameter A120 is the best indication in a diagnosis of glaucoma when measuring
      NFLT by OCT.

PMID- 15148736
TI  - [The effect of substituting latanoprost 0.005% for unoprostone 0.12%].
AB  - PURPOSE: To evaluate the effect of substituting latanoprost(LAT) 0.005% for
      unoprostone(UNO) 0.12% after a trial of unilateral treatment. METHODS: We treated
      30 patients with primary open-angle glaucoma(n = 8), ocular hypertension (n = 1),
      or normal-tension glaucoma(n = 21) with UNO for 4 weeks in one eye and then
      substituted LAT for UNO. Four weeks later we measured the intraocular
      pressure(IOP) in the ipsilateral eye. RESULTS: The mean baseline IOP level was
      18.6 +/- 3.8(mean +/- standard deviation) mmHg. The mean IOP levels(reduction
      rates) after UNO and LAT therapy were 16.7 +/- 3.1 mmHg (16.6%) and 14.1 +/- 3.2
      mmHg (28.9%), respectively(p < 0.001). All patients who responded to UNO also
      responded to LAT; however, 55% of those who did not respond to UNO responded to
      LAT. CONCLUSIONS: If LAT is substituted for UNO, it can be predicted that 63.3%
      of the patients will respond.

PMID- 15148739
TI  - [A case of von Hippel-Lindau disease with papillary capillary hemangioma treated
      by photodynamic therapy].
AB  - BACKGROUND: Laser photocoagulation of papillary hemangioma in von Hippel-Lindau
      disease often causes visual loss. Therefore, we applied photodynamic therapy for
      one patient. CASE: A 36-year-old male had 3.2 x 2.6 mm capillary hemangioma of
      the optic disc associated with a fibrovascular membrane and exudative retinal
      detachment involving the whole macular area in his left eye. His visual acuity
      was 0.08. TREATMENT: Two days after the intravenous injection of 2 mg/kg of
      hematoporphyrin derivatives, the eye was irradiated with a dye laser of 630 nm
      wavelength, with irradiance of 637 mW/cm2 and a radiant exposure of 150-250
      J/cm2. The exudative retinal detachment and hemorrhage in the tumor increased
      from day 1, but the tumor and exudative changes began to resolve after 3 weeks.
      The fibrovascular membrane was removed by vitrectomy. Three years after the
      treatment, the tumor was completely resolved, but the patient's visual acuity was
      0.1 due to atrophy of the optic nerve and pigment epithelium of the macula.
      CONCLUSION: Although further investigation on optimal radiance avoiding damage to
      the optic nerve is still needed, photodynamic therapy is a promising therapeutic
      option for papillary hemangioma.

PMID- 15148738
TI  - [A case of acute angle-closure glaucoma secondary to annular ciliochoroidal
      detachment after unsutured cataract surgery].
AB  - BACKGROUND: We report a patient with acute angle-closure glaucoma secondary to
      annular ciliochoroidal detachment after unsutured cataract surgery. CASE: An 82
      year-old man was diagnosed with bilateral shallow central anterior chamber depth,
      flat peripheral anterior chamber, and elevated intraocular pressure. One day
      previously he had undergone uncomplicated unsutured cataract surgery in the right
      eye and eight days previously, in the left eye. Ultrasound biomicroscopy revealed
      annular ciliochoroidal detachment in both eyes. Treatment with intravenous methyl
      prednisolone deepened the anterior chamber and reduced intraocular pressure.
      CONCLUSION: Annular ciliochoroidal detachment may lead to anterior rotation of
      the ciliary body and angle-closure. This clinical entity is indistinguishable
      from malignant glaucoma when the fundus cannot be visualized.

PMID- 15148740
TI  - [Malignancy of hematopoetic system in the elderly--acute myelogenous leukemia].

PMID- 15148741
TI  - [Adrenomedullin and organ protection].

PMID- 15148742
TI  - [Geriatric syndrome and geriatric medicine].

PMID- 15148743
TI  - [Present status and perspective of comprehensive geriatric assessment in Japan].
AB  - Comprehensive geriatric assessment (CGA) is an important strategy to maintain
      activities of daily living and quality of life of elderly patients. It assesses
      physiological, psychosocial, and cognitive aspects of elderly. To carry it out
      effectively, not only is accurate the assessment but also to do appropriate
      recommendation and implementation are essential. In Japan, although the concept
      of CGA has been introduced and evaluated for elderly patients and also employed
      essentially in long-term care insurance, its application in the acute care
      setting of the elderly is still limited. This report, examines the present status
      and perspective of CGA application in Japan, through experiences in our
      university hospital and analysis of presentations from the Annual Meeting of the
      Japan Geriatric Society 2003.

PMID- 15148744
TI  - [Insulin therapy in elderly patients with diabetes mellitus].
AB  - Insulin therapy is an effective measure of improving glucose control even in
      elderly patients with type 2 diabetes. However, it is controversial whether
      insulin therapy does disturb the quality of life (QOL) as well as cognitive
      function in the elderly. In our previous study of 455 diabetic patients, the well
      being as assessed by the morale scale was similar in three treatment groups. In
      contrast, the symptom-burden, social burden, and worry about diabetes as assessed
      by the Elderly Diabetes Burden Scales was more increased in insulin-treated group
      as compared to the diet-treated group after adjustment for age, gender, HbAlc,
      frequency of hypoglycemia, microangiopathy, macroangiopathy, and social support.
      In another study of 213 patients, MMSE scores were similar among treatment
      groups, while attention and learning were most impaired in insulin-treated groups
      after adjustment for age, gender, HbAlc, and duration of diabetes. Although the
      mechanism for the association between insulin treatment and cognitive impairment
      is unknown, hyperglycemia, hypoglycemia, and cerebral complications in insulin
      treated patients may be possible explanations. Whatever mechanism may be
      involved, hypoglycemia should be considered especially if unexpectedly low HbAlc
      (< 6.5%) is observed or atypical neuropsychological symptoms appear. It is
      unknown how insulin withdrawal is successful in elderly diabetic patients. Using
      rapid or ultrarapid insulin injections three times daily, good glucose control
      achieved the goal of plasma glucose level of < 140 mg/dl before meals and at
      bedtime. Then, insulin therapy was converted to oral treatment of glimepiride (2
      to 6 mg/day) and/or voglibose (0.6 mg/day) in 30 patients with poorly controlled
      Type 2 diabetes. About 83% of the patients were successful in the insulin
      withdrawal according to the criteria of HbAlc levels after two months < 8.0%.
      After removal of glucose toxicity, insulin withdrawal should be attempted to
      improve QOL in elderly patients with diabetes mellitus.

PMID- 15148745
TI  - [Clinical gene therapy for peripheral arterial disease].

PMID- 15148746
TI  - [Cell therapy for vascular regeneration in the elderly patients].

PMID- 15148747
TI  - [The regenerative therapy of heart failure with adult stem cells and cell
      transplantation].

PMID- 15148748
TI  - [Cell transplantation and regenerative therapy for neurological disorders:
      treatment for the elderly].

PMID- 15148749
TI  - [Validity of the Rivermead Behavioural Memory Test for evaluation of everyday
      memory function in patients with mild cognitive impairment].

PMID- 15148752
TI  - [A preliminary study to detect the patients with early dementia in a community-
      using Syndrome Kurz Test].

PMID- 15148751
TI  - [The role of brain functional imaging on early diagnosis of dementia].

PMID- 15148750
TI  - [In vivo imaging of amyloid plaques in the brain].
AB  - The pathological hallmark of Alzheimer's disease (AD) is the deposition of senile
      plaques (SPs) and neurofibrillary tangles. The deposition of SPs, which initially
      occurs in the neocortex, is regarded as the critical event for the pathogenesis
      of AD. Previous pathological studies indicated that the earliest deposition of
      SPs is suspected to occur before any detectable cognitive decline. Therefore,
      noninvasive imaging of brain SPs is considered to be an ideal diagnostic method
      for presymptomatic detection of AD. For in vivo detection of SPs in the brain, a
      lipophilic probe that can selectively binds SPs is indispensable to the
      examination using positron emission tomography (PET) or single photon emission
      computed tomography (SPECT). For this purpose, many kinds of amyloid binding
      agents have been developed, such as FDDNP, BTA-1, IMPY. We have also developed a
      series of promising compounds for in vivo imaging of amyloid deposits. One of
      these compounds, compound-A, achieves high binding affinity for A beta fibrils.
      This agent also showed abundant initial brain uptake and short brain clearance
      half-life in normal mice. Furthermore, to investigate the in vivo binding
      property of compound-A to amyloid plaques, compound-A was intravenously
      administered to APP transgenic mice. Brain slices at 120 min post injection
      demonstrated specific binding of compound-A to amyloid plaques in the brain.
      These data emphasize the potential usefulness of compound-A as in vivo imaging
      probe for early diagnosis of AD.

PMID- 15148753
TI  - [Epidemiology of mild cognitive impairment (MCI) among the community-dwelling
      elderly--findings from the Nakayama Study].

PMID- 15148754
TI  - [Geriatric medicine and long-term care insurance].
AB  - Long-term care insurance (LCI) started from April 2000 in Japan. LCI now occupies
      a central position in the health care of the aged. We reviewed all original
      papers and reports on LCI published in 1996-2002. At the end of 2002, we searched
      for papers on LCI in a computer database using the keyword of LCI, and found
      3,606 papers. Authors and contents of each paper were categorized using 54 kinds
      of keywords. Frequent authors were government agencies, care managers, physical
      therapists, and physicians. When we analyzed these papers according to the places
      where LCI was used, more than 50% of reports concerned LCI at home. Most frequent
      keywords were Government/LCI system. Regional health, Physician' assessment and
      grades for care. Care management, Care manager, and Rehabilitation. Care manager
      was less observed after the start of LCI. In contrast, the use of keywords
      including Care service. Dementia, Geriatric syndrome, Nurse, Institutional
      medicine, Hospital care, Medicine for the aged, Terminal care, Dialysis therapy,
      Abuse of the aged, and Caregiver burden were increased after LCI. At the
      beginning of LCI, main concerns are on the new LCI system. However, more
      individual issues in the care of the aged are now discussed. New issues such as
      Abuse of the aged and Caregiver burden have been recently raised. From these
      observations, the role of geriatric medicine seems also to be changing after the
      induction of LCI. We would now contribute actively to crucial aspects of LCI,
      such as comprehensive assessment of the aged, functional medical network with
      care staffs, and new therapeutic approaches to each geriatric syndrome.

PMID- 15148755
TI  - [Overview of the Japanese long-term care insurance system current and future].

PMID- 15148756
TI  - [The dementia care in the long-term care insurance system].

PMID- 15148757
TI  - [The present and task of the care-manager system after the 5th years].

PMID- 15148758
TI  - [The changes after long-term care insurance system and the problems in home
      care].

PMID- 15148759
TI  - [Cross-validation of the short version of the Japanese version of the Zarit
      Caregiver Burden Interview (J-ZBI_8)].
AB  - This study was aimed at confirming the cross-validity and construct validity of
      the short version of the Japanese version of the Zarit Caregiver Burden Interview
      (J-ZBI_8) developed by Arai and colleagues. A total of 169 family members caring
      for disabled elderly were assessed by a self-administered questionnaire which
      included the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI).
      Cronbach's alpha of the J-ZBI_8 was 0.88, indicating a high reliability of this
      instrument. A confirmatory factor analysis revealed that the two factor model of
      J-ZBI_8 fitted the data. Pearson's correlation coefficient between J-ZBI_8 and J
      ZBI was 0.92; and the correlation coefficient between J-ZBI_8 and item 22 (a
      single global burden) was 0.66. These data indicated that J-ZBI_8 had a high
      concurrent validity. The J-ZBI_8 was found to be significantly correlated with
      Barthel Index, duration of caring, hours of caregiving/day, physical fatigue and
      mental fatigue among caregivers, but not with the duration of caring (months).
      Caregivers of disabled elderly who did not have any behavioral disturbances had a
      significantly lower J-ZBI_8 score than those who were caring for elderly with
      such behaviors. Also, caregivers who declared that they did not abuse disabled
      elderly had a significantly lower J-ZBI_8 score than those who replied they
      abused them, when compared by t-test. These results indicated that J-ZBI_8 had a
      high construct validity. It is concluded that the J-ZBI_8 had a high cross
      validity and construct validity. This instrument can thus facilitate the
      assessment of family caregiver burden in clinical settings.

PMID- 15148760
TI  - [Effect of gamma-aminobutyric acid-rich germinated brown rice on indexes of life
      style related diseases].
AB  - We examined the effects of gamma-aminobutyric acid-rich germinated brown rice
      (germinated brown rice) on principal indexes of life-style related diseases in 67
      volunteers aged 71 +/- 8. They were divided into two groups; germinated brown
      rice group, which had an equal amount of the germinated brown rice to polished
      rice for 11 to 13 months, and control group, which had polished rice alone for
      the same period. Differences of indexes before and after the examination between
      the two groups were compared. Significant increases in body fat ratio, hemoglobin
      A1c and mean red cell volume and a significant decrease in mean red cell
      hemoglobin concentration were observed in the germinated brown rice group.
      However, there was no difference of changes in body mass index, blood pressure,
      serum lipid, hepatic and renal functions, bone metabolic markers, bone density,
      depression score, red blood cell counts, hemoglobin, hematocrit, and homeostasis
      model assessment of insulin resistance between the two groups. These findings
      suggested that germinated brown rice might not improve glucose metabolism.

PMID- 15148761
TI  - [Care assessment related to dysphagia in the frail elderly].
AB  - The purpose of the present study was to investigate some symptoms related to
      dysphagia, comprehensive health status, and oral care in the frail elderly. The
      subjects were 92 elderly individuals (30 men, 62 women) above 65 years in a
      nursing home. The risk factors of dysphagia were evaluated by 15 items of self
      assessment and 18 items of assessment by their caregivers. Both assessments
      contained 12 identical items. Basic ADL, cognitive status, and QOL were evaluated
      by the Barthel index, HDS-R, and PGC morale scale respectively. The status of
      oral care was evaluated by the frequency of tooth cleaning a day and the number
      of total anaerobic bacteria or streptococci in the dental plaque. "Chewing
      difficulty with hard food" was frequently found (21.74%) in the self-assessment,
      while "fever" was frequently found in the caregiver's assessment (20.65%). Also,
      in the duplicate items in both assessments, "anamnesis of pneumonia" showed a
      high agreement (k = 0.85), while "decline of appetite" had a low agreement (k =
      0.27). These results suggest that dual assessment is effective to detect
      dysphagia. We also investigated the relationship among dysphagia, comprehensive
      health status, and oral hygiene. The status of dysphagia was related only to the
      Barthel index (p < 0.01). These results suggest that subjects with decreased
      basic ADL tend to have some risk factors related to dysphagia, and that subjects
      with dysphagia risk factors need to improve oral care to prevent aspiration
      pneumonia.

PMID- 15148763
TI  - [A case report of primary gastric adult T cell lymphoma].
AB  - A 70-year-old woman was admitted to our hospital for treatment of abdominal
      tumor. She had complained of left abdominal pain, body weight loss and slight
      fever. Upper gastrointestinal endoscopy revealed on profounding ulcerous and
      upheaval lesion from the upper part of gastric body to the antrum. The
      pathological diagnosis of the biopsy specimens was T-cell lymphoma and proviral
      DNA (GAG) of HTLV-I was demonstrated in the biopsy specimens. Although the
      patient was serologically positive for anti-human T-lymphotrophic virus type I
      (HTLV-I) antibody, there were no leukemia/lymphoma cells in the peripheral blood
      or systemic lymphadenopathy. Primary gastric Adult T-cell leukemia/lymphoma
      (ATLL) was diagnosed. Although she received chemotherapy, the response was poor.
      The prognosis of lymphoma-type ATL is known to be extremely poor. This disease is
      frequent in aged people. Although gastrointestinal involvement is frequent in
      ATLL, primary gastric ATLL is rare. We report this rare case with primary gastric
      ATLL and reviewing 13 cases previously reported.

PMID- 15148762
TI  - [Relationship between obesity and atherosclerotic risk in elderly type 2 diabetic
      patients].
AB  - The relationship between obesity and incidence of stroke and ischemic heart
      disease is known to be weaker in elderly people compared with younger people. The
      relationships between obesity and atherosclerotic risk factors have been reported
      to decrease with age in healthy subjects. In order to clarify whether obesity
      influences atherosclerotic risk factors in elderly diabetic patients, we
      investigated the relationship between body mass index (BMI) and atherosclerotic
      risk factors in elderly (65 years or more) patients (61 men and 65 women) with
      type 2 diabetes mellitus. BMI significantly correlated with blood pressure, serum
      triglyceride, uric acid and sialic acid concentrations and negatively with
      duration of diabetes and serum HDL cholesterol concentration. These
      relationships, except that with serum uric acid concentration, were still
      significant after adjustment for sex and age. Diabetic subjects with a BMI of 25
      or over showed significantly higher arterial pressure and serum triglyceride and
      sialic acid levels and lower serum HDL cholesterol level compared with diabetic
      subjects with a BMI of below 22. These results suggest that obesity increases the
      atherosclerotic risk even at higher ages in diabetic patients and that correction
      of obesity helps prevention of atherosclerosis in elderly diabetic patients.

PMID- 15148764
TI  - [A case of pure autonomic failure (PAF) with sleep apnea syndrome (SAS) and
      successful treatment of dysautonomia with nasal continuous positive airway
      pressure (CPAP)].
AB  - A 72-year-old man was admitted to our hospital due to dysuria and frequent
      syncope. The patient had been well until the age of 70 years, when he began with
      these symptoms and neurogenic bladder was diagnosed in the other hospital. On
      admission, neurological examinations revealed no abnormal findings except
      blepharoptosis, anisocoria and orthostatic hypotension. Frequent apnea was
      evident during sleep. Autonomic function tests showed mainly sympathetic
      postganglionic dysfunction. Brain magnetic resonance imaging showed lacunar
      infarctions without cerebello-pontine atrophy or abnormal signals of the basal
      ganglia. We diagnosed pure autonomic failure (PAF) with sleep apnea syndrome
      (SAS). After starting nasal continuous positive airway pressure (CPAP) for SAS,
      his sneezing and sleep apnea drastically improved. Interestingly, CPAP also
      decreased the severity of orthostatic hypotension and syncope. Ambulatory blood
      pressure monitoring (ABPM) showed remarkable improvement in diurnal fluctuation
      of blood pressure after CPAP therapy. Although SAS is frequently associated with
      Shy-Drager syndrome but not with PAF, patients with PAF had been reported to have
      degenerative changes in the central nervous system overlapping with Shy-Drager
      syndrome or Lewy body disease. This case raised the possibility that nasal CPAP
      may be useful for orthostatic hypotension as well as SAS in neurodegenerative
      diseases.

PMID- 15148766
TI  - The impact of angiogenesis on the prognosis of advanced renal cell carcinomas.
AB  - We studied the relationship between angiogenic factors and clinical responses in
      advanced renal cell carcinomas (RCCs) and evaluated the angiogenic factors to
      clarify the potential impact of these factors on the cancer-specific survival.
      From January 1990 to December 2000, 148 patients underwent a nephrectomy for RCCs
      at our institution. Of the 32 patients who had distant metastasis, 17 met the
      histopathologic analysis requirements for an immuno-histochemical investigation.
      Fifteen of them were administered interferon-gamma and the remaining two patients
      were added to interferon-alpha and eight of seventeen patients also underwent
      radiation therapy. Both thymidine phosphorylase (TP) and Factor VIII
      immunostaining were performed. The overall survival rates at 1, 5 and 10 years
      were 82.4%, 30% and 30%, respectively. Three of these patients were diagnosed
      with lung metastasis and a complete response was seen in two, while a partial
      response was observed in one. In addition another patient who was diagnosed with
      bone metastasis also showed a partial response (group A). The remaining 13
      patients showed progressive disease (group B). Group A had a higher TP-positive
      ratio (TP-PR) than that of group B. A multivariate analysis of the
      clinicopathologic data showed that a positive mean vascular area (PMVA) could be
      an independent factor regarding the potential impact of these factors on a long
      survival in advanced RCCS. PMVA was thus found to be an independent factor
      regarding the prognosis with advanced RCCs.

PMID- 15148765
TI  - Clinicopathological outcome of radical retropubic prostatectomy for 200 men with
      prostate cancer in a single institution in Japan.
AB  - The objective of this study was to retrospectively evaluate the
      clinicopathological outcome of radical retropubic prostatectomy (RRP) performed
      at a single institution in Japan. A consecutive series of 200 patients with
      prostate cancer who underwent RRP and pelvic lymphadenectomy between March 1985
      and April 2003 were included in this study. The median age at RRP and the
      observation period were 69 years old and 43 months, respectively.
      Clinicopathological findings were reviewed to determine parameters providing
      predictive information about biochemical recurrence-free, cause-specific, and
      overall survivals. The pathological stage was pT0 in 7 patients (3.5%), pT2a in
      43 (21.5%), pT2b in 58 (29.0%), pT3a in 42 (21.0%) pT3b in 36 (18.0%), and pT4 in
      14 (7.0%). Lymph node metastasis was detected in 32 of 200 patients (16.0%).
      Forty-seven patients (23.5%) received neoadjuvant hormonal therapy, while 48
      (24.0%) underwent hormonal therapy alone or hormonal therapy plus radiotherapy
      following RRP as an adjuvant treatment. During the observation period, 4 patients
      (2.0%) died of prostate cancer, 11 (5.5%) died of other diseases and biochemical
      recurrence occurred in 23 (11.5%), when biochemical recurrence was defined as
      prostate specific antigen (PSA) persistently greater than 0.4 ng/ml. Five-year
      biochemical recurrence-free, cause-specific, and overall survival rates were
      83.6%, 97.7% and 91.4%, respectively. Furthermore, multivariate analyses showed
      that lymph node metastasis or clinical stage was an independent predictive factor
      for cause-specific or overall survival, respectively. These findings suggest that
      it would be possible to achieve a favorable cancer control for patients with
      localized prostate cancer, including locally advanced cases, by the RRP-based
      combination therapies.

PMID- 15148767
TI  - [Chronological changes of incidence rates, clinical stages and pathological
      differentiation of prostate cancer in Gunma Prefecture, Japan].
AB  - Prostate cancer is the most common urogenital cancer, and is increasing rapidly.
      We performed an epidemiological study on prostate cancer in Gunma Prefecture,
      Japan. Registration of prostate cancer patients diagnosed at clinics and
      hospitals in and around Gunma Prefecture was started at Gunma University in 1985.
      The epidemiological characteristics of prostate cancer patients in Gunma
      Prefecture were analyzed by these data. The incidence and crude incidence rates
      have increased five-fold, from 114 and 12.0 in 1985 to 539 and 53.9 in 2000,
      respectively. The age-adjusted incidence rate (adjusted to the world population)
      was increased three-fold, from 8.3 in 1985 to 24.2 in 2000. The age-specific
      incidence rate showed an increase with age. The cancers in clinical stages A and
      D decreased, while those in stages B and C increased. No change in distribution
      was observed in pathological differentiation. Prostate cancer has increased
      rapidly during these 16 years in Gunma Prefecture. It is important to perform PSA
      testing aggressively in males age 50 or older, and detect prostate cancer in an
      early stage.

PMID- 15148768
TI  - [The significance of urine cytology three consecutive days after transurethral
      resection as a predictor of superficial bladder cancer recurrence].
AB  - To determine whether there was any correlation between recurrence of superficial
      bladder cancer and the results of urinary cytology examined for 3 consecutive
      days after transurethral resection of the bladder cancer (TURBT), we
      retrospectively studied 64 patients with newly diagnosed Ta/T1 transitional cell
      carcinoma (TCC) of the bladder who had previously undergone TURBT. Urine cytology
      samples were reported as negative (class I, II) or positive (class III, IV, V).
      We used the Kaplan-Meier method to calculate the non-recurrence rate, and Cox
      proportional hazard models to determine the prognostic significance of clinical
      and pathological findings. If any sample among the three consecutive cytology
      examinations was positive, we defined the case as positive. After a mean follow
      up of 19.5 months, 22 cases (34.4%) demonstrated recurrence probabilities of
      24.1% and 42.3%, at 12 and 24 months, respectively. Of the positive cytology
      group (n = 33), 15 patients (45.5%) had recurrent tumor, while in the negative
      group (n = 31), only 7 cases (22.6%) developed recurrence. Multivarite analysis
      demonstrated that tumor size (p = 0.0022, Hazard ratio 8.9316), result of urine
      cytology for three consecutive days after TUR (p = 0.0051, Hazard ratio 4.5728),
      and age (p = 0.0124, Hazard ratio 3.7652) were associated with tumor recurrence.
      We suggest that positive results on urinary cytology for three consecutive days
      after TUR are indicative for tumor recurrence.

PMID- 15148769
TI  - [Bellini duct carcinoma of the kidney: a case report].
AB  - A case of Bellini duct carcinoma is reported. A 70-year-old man visited our
      hospital because of gross hematuria and left flank pain. Although no abnormality
      was found on ultrasonography, drip infusion pyecography, computed tomographic
      scan and cystoscopy. However class IV was suspected based on urinary cytology.
      Magnetic resonance imaging showed an irregular pattern in the left upper kidney.
      Ureterscopic biopsy revealed transitional cell carcinoma and class V was
      suspected on the urinary cytology of the left renal pelvis. Under the
      preoperative diagnosis of a left renal pelvic tumor, left nephroureterectomy was
      performed. The histopathological diagnosis with immunohistostaining was Bellini
      duct carcinoma. No evidence of recurrence or metastasis was noted 9 months after
      surgery without any adjuvant therapy.

PMID- 15148770
TI  - [Two cases of ammonium acid urate urinary stones related to anorexia nervosa and
      laxative abuse].
AB  - We report two cases of urolithiasis related to anorexia nervosa and laxative
      abuse. Case 1: A 21-year-old woman was referred to our hospital because of left
      flank pain. A left ureteral stone, 10 x 6 mm in size, was successfully fragmented
      by extracorporeal shock-wave lithotripsy (ESWL), but she experienced repetitive
      formation of bilateral urinary stones and double J stent encrustation which
      required 13 sessions of ESWL, one session of transurethral ureterolithotripsy and
      one session of cystolithotripsy over a period of 5 years. All stones were
      comprised of pure ammonium acid urate. It was later revealed that she was
      diagnosed with anorexia nervosa at 15 years old and had suffered from laxative
      abuse (bisacodyl, 300-500 mg/day) ever since. Case 2: A 18-year-old woman was
      referred to our hospital because of left lower abdominal pain. A left renal
      stone, 15 x 10 mm in size, was successfully fragmented by ESWL, but she had
      double J stent encrustation which was managed by cystolithotripsy. All stones
      were comprised of pure ammonium acid urate. She was later diagnosed with anorexia
      nervosa and it turned out that she had suffered from an eating disorder and
      laxative abuse (bisacodyl, 200 mg/day) since the age of 15 years. Both patients
      had marked decrease in urine volume, hyponatremia and hypokalemia. Anorexia
      nervosa and laxative abuse should be suspected whenever a woman has an ammonium
      acid urate stone in sterile urine because the treatment of these disorders is
      crucial to the prevention of repetitive formation of urinary stones.

PMID- 15148771
TI  - [Complete avulsion of ureter caused by abdominal blunt injury: a case report].
AB  - A 21-year-old woman who had been injured in a traffic accident appeared with
      abdominal pain and macroscopic hematuria. Computed tomography (CT) performed 6
      hours after the injury showed extravasation of contrast medium in the right
      retroperitoneal space. Retrograde pyelography (RP) showed the interruption of
      right ureter at the site of ureteropelvic junction. We performed an abdominal
      operation 15 hours after the injury under the diagnosis of right ureteral
      avulsion. We observed a completely separated right ureter at the ureteropelvic
      junction, and performed an end to end anastomosis. The patient was discharged
      three weeks after surgery, and has not had any problems for three years.

PMID- 15148772
TI  - [A case bilharziasis in a Japanese male].
AB  - Bilharziasis is an endemic disease distributed mostly in African countries and
      the Middle East, and causes severe disturbances of urinary tract secondarily.
      Although it used to be a very rare disease in Japan, modern human mobility and
      jet travel have brought this tropical disease into our country far from endemic
      areas. A 25-year-old Japanese male presented to our hospital with macroscopic
      hematuria. He had an experience of traveling to Malawi two years before.
      Cystourethroscopy demonstrated so-called 'bilharzial tubercles', many yellowish
      specks of mucosa at the posterior wall and dome of the bladder. The diagnosis of
      bilharziasis was made by detection of Schistosoma haematobium eggs in urine and
      histological specimen obtained by transurethral biopsy. In this case,
      radiographic and pathological examinations revealed neither obstructive uropathy
      nor urothelial malignancy. He was treated with praziquantel, and the disease is
      under good control.

PMID- 15148773
TI  - [Angioplasty for the intimal dissection of graft artery immediately after blood
      reflow: a successful case of renal transplantation].
AB  - A 58-year-old woman, who had been suffering from chronic renal failure on
      hemodialysis since 1999, underwent living renal transplantation on January 14,
      2003. The donor was her husband, and his left kidney was resected by a hand
      assisted retroperitoneoscopic technique. Vascular clamps were removed after
      vascular anastomoses, but the color of two-thirds of the graft back side was
      dark, and urine excretion was not observed for 1 hour. The intimal dissection of
      the graft artery developed false lumen that occluded the blood flow to the
      transplanted kidney. The graft was resected from the recipient, and an
      angioplasty was performed for the false lumen of the graft artery after the
      second cold preservation. The graft with repaired artery was re-transplanted, and
      urine excretion was observed immediately after operation. Total ischemia time was
      5 hours. Clinicopathological acute rejection episode and stenosis of graft artery
      did not occur for 6 months after operation. The intimal dissection of graft
      artery might occur at the time of catheterization on the perfusion for cold
      preservation and/or vascular anastomosis.

PMID- 15148774
TI  - [Cutaneous epithelioid granulomas caused by subcutaneous infusion of leuprorelin
      acetate: a case report].
AB  - A 73-year-old man presented with an ulcer and a subcutaneous nodule where he was
      receiving leuprorelin acetate injections to treat his prostatic carcinoma.
      Pathological findings of a skin biopsy showed many epithelioid granulomas with
      multinuclear giant cells, which contained small vacuoles. Recently, these lesions
      have been suggested to be caused by a type IV allergic response to the copolymer
      of lactic and glycolic acids used as a vehicle for drug administration. When
      urologists treat a prostatic adenocarcinoma with subcutaneous infusion of
      leuprorelin acetate, they should be aware of this potential side effect of the
      drug because the resulting granulomar formation may interfere with the effect of
      the drug. If patients suffer from subcutaneous nodules, urologists should
      consider changing the drug to an other type of luteinizing hormone-releasing
      hormone analogues such as goserelin acetate. This reaction to leuprorelin acetate
      has been reported in only seven cases including our case.

PMID- 15148775
TI  - [Bladder stone formation caused by a Stamey cuff as the nidus indwelt 16 years
      ago].
AB  - Although foreign bodies left in the body may remain asymptomatic for long
      periods, they may also cause various complications. We present a case of a Stamey
      cuff placed in the retroperitoneal space, which remained asymptomatic for 16
      years in a 62-year-old woman. When a vesical calculi formed, it caused voiding
      pain in the lower abdomen. She underwent transurethral cystolitholapaxy. The
      nidus of the stone was a Stamey cuff used in the Stamey procedure performed 16
      years before. Open cystotomy was needed to remove it. Convalescence was
      uneventful and she had no complaints on urination. The possibility of calculous
      formation should be raised when there are symptoms on urination in a female with
      a history of pelvic surgery.

PMID- 15148776
TI  - [A case of squamous metaplasia of the ureter].
AB  - This paper reports a 73-year-old man who developed ureteral squamous metaplasia.
      Preoperative drip infusion pyelography showed a ureteral tumor with a major axis
      measuring 2.5 cm, which had a smooth surface and a broad base. Computed
      tomography findings suggested that the lesion might be a submucous mesodermal
      tumor or inverted papillary transitional cell carcinoma. Therefore,
      retroperitoneal laparoscopic left nephroureterectomy was performed.

PMID- 15148777
TI  - [Three cases of congenital penile curvature].
AB  - Congenital penile curvature is a rare disease. We experienced three cases of
      congenital penile curvature. Penile curvature was recognized in all cases from
      adolescence. Induration and cordee were not palpable in the penis of all cases.
      We performed modified Nesbit method in all cases. Penile curvature, however,
      recurred in 1 case.

PMID- 15148779
TI  - [A case of fistula between the urinary bladder and an ovarian dermoid cyst].
AB  - A 20-year-old woman was referred to our hospital for further evaluation on
      persistent pyuria. Physical examination showed a tender solid suprapubic mass.
      Computed tomography showed a right ovarian multilocular cystic tumor just above
      the urinary bladder. Cystoscopy showed pus leakage from an orifice in a
      hemisphere protrusion of the bladder wall. A small catheter could be inserted
      into the orifice. It revealed a fistula 4 cm in length between the right ovarian
      tumor and the vesical cavity. The tumor and the adjacent thickened bladder wall
      with an abscess and fistula were resected en bloc. Also a small left ovarian cyst
      was enucleated. Histopathological examination showed bilateral ovarian dermoid
      cysts, abscess formation, and marked inflammatory change around the fistula in
      the vesical wall. The fistula was thought to be the consequence of infection of
      the ovarian cyst.

PMID- 15148778
TI  - [Licorice of 'shakuyaku kanzou tou' induced pseudoaldosteronism].
AB  - We report a case of pseudoaldosteronism induced by licorice in a kampo medication
      'Shakuyaku Kanzou Tou' that was diagnosed after relief of urinary retention due
      to benign prostatic hypertrophy (BPH). A-71-year-old man was admitted to our
      hospital due to urinary retention. At admission, he had hypertension and leg
      edema, but serum potassium was in the normal range. One day after admission,
      hypokalemia was recognized. He was taking "Shakuyaku Kanzou Tou", a Chinese
      medicine that contains glycyrrhizin. So we suspected pseudoaldosteronism and had
      him stop taking it. Computed tomography did not reveal any adrenal tumor. Plasma
      rennin activity and aldosterone level were suppressed. Gradually, hypertension
      and leg edema improved and serum potassium became within the normal range. We
      diagnosed the case as pseudoaldosteronism induced by licorice of 'Shakuyaku
      Kanzou Tou'. Since we suspected BPH to be the cause of urinary retention, we
      performed transurethral resection of prostate. After surgery, he was able to void
      smoothly.

PMID- 15148781
TI  - [Radiation medicine and medical physics].

PMID- 15148780
TI  - [Multiple metastases of the penile cancer: an experience of combination
      chemotherapy].
AB  - A 49-year-old man with penile cancer (cT3N1M0) was referred to our hospital. The
      pathologic diagnosis was squamous cell carcinoma. The patient underwent penectomy
      and bilateral inguinal lymphadenectomy without postoperative adjuvant therapy.
      Six months later, we found multiple metastases of the penile cancer in the lungs.
      The patient was then treated with combination chemotherapy of cisplatin,
      methotrexate, bleomycin. However, the tumors were aggressive and did not respond
      to the therapy. We discuss the use of combination chemotherapy in the case of
      advanced penile cancer.

PMID- 15148782
TI  - [Practice and future aspects of nuclear cardiology].
AB  - The field of nuclear cardiology has demonstrated sustained growth in recent years
      owing to its increasingly recognized value for clinical applications and patient
      management. Computer advances in this field have allowed the technology of ECG
      gated SPECT to become a routine part of nuclear cardiology. In our laboratory,
      myocardial perfusion and left ventricular function during stress (bicycle
      exercise or dobutamine infusion) were analyzed in a single examination by means
      of gated SPECT. This procedure has the potential to provide comprehensive
      information with which to evaluate patients with ischemic heart disease. 123I
      BMIPP is a branched-chain free fatty acid, and its distribution could provide
      useful information about metabolic function in patients with ischemic heart
      disease (including minor infarction). The solid-state gamma camera 2020 tc Imager
      is now commercially available and has been clinically applied. The lightweight
      and compact design of the camera allows mobility of the unit between departments
      and floors. This technique would be useful for assessing left ventricular
      function under emergency conditions. In this paper, the techniques of
      examinations are described, and potential assessments are addressed. We look
      forward to further advances in nuclear cardiology for the accurate diagnosis and
      management of patients with various cardiac diseases.

PMID- 15148783
TI  - [Comparison of ERCP and MRCP: invasiveness and cost].
AB  - The purpose of this study was to compare ERCP and MRCP in terms of invasiveness
      and cost. A questionnaire regarding patient satisfaction was distributed to 23
      ERCP patients and 63 MRCP patients. The practical cost of each examination and
      total yearly cost for 2002, including medication costs for post-ERCP
      pancreatitis, were calculated. On a trial basis, the total yearly cost for 2002
      was also calculated as a percentage of the cost in 1996. Results of the
      questionnaire showed that patients tended to favor MRCP over ERCP. In our
      hospital, the practical costs of MRCP and ERCP were 2063 points and 3964 points,
      respectively. Medication costs for pancreatitis corresponded to about 3% of the
      total yearly cost for ERCP. The total yearly costs for both examinations and the
      medication costs for pancreatitis were about 1,360,000 points. The result of
      trial calculation with the examination percentage of 1996 was about 1,950,000
      points. The results of our study demonstrated that MRCP is a noninvasive
      examination for patients and that its popularization contributed to a reduction
      in medical costs. For further popularization of equipment and advanced imaging
      methods, careful assessment of examination costs is important.

PMID- 15148784
TI  - [Evaluation of strongly hyperintense area in breast lesions on fat-suppressed T2
      weighted images correlated with histopathology].
AB  - The purpose of this study was to correlate strongly hyperintense areas(SHI) in
      breast lesions on FS-T2WI with histopathology and to evaluate the usefulness of
      the distribution patterns of SHI in the differentiation of benign and malignant
      breast lesions. MR imaging with pathological correlation was available in 157
      breast lesions of 153 patients. The distribution patterns of SHI were classified
      into seven types. SHI on FS-T2WI was identified in 36 of 157 breast lesions. The
      irregular and inhomogenous types corresponded to various histological features
      and were only seen in malignant lesions. The central type corresponded to central
      necrosis and was only seen in 2 solid-tubular carcinomas. The crescent type
      corresponded to peripheral fluid collection in the intracystic tumor. The septal
      type corresponded to fibromyxoid stroma with fibrous septations in the lesions
      except for one cavernous hemangioma, and was only seen in benign lesions. The
      smooth type corresponded to mucinous pool, fibromyxoid stroma, and ductal
      dilatation and did not contribute to differentiation between benign and malignant
      lesions only on FS-T2WI. SHI in breast lesions on FS-T2WI pathologically
      corresponded to mucin, fibromyxoid change, necrosis, and ductal dilatation.
      Evaluation of patterns of SHI is useful in differentiating between benign and
      malignant lesions.

PMID- 15148786
TI  - [Radiological reporting system developed with FileMaker-Pro: cooperation with
      HIS, RIS, and PACS].
AB  - This article briefly describes our original radiological reporting system. This
      system was developed with the widely used database software FileMakerPro (ver
      5.5). The reporting system can obtain information about patients and examinations
      from a radiology information system(RIS) by the Open DataBase Connectivity(ODBC)
      technique. By clicking the button on the reporting system, the corresponding
      DICOM images can be displayed on a picture archiving and communication
      system(PACS) workstation monitor. Reference images in JPEG format can be easily
      moved from PACS to the reporting system. Reports produced by the reporting system
      are distributed to the hospital information system(HIS) in Portable Document
      Format(PDF), through another web server. By utilizing the capacity of
      FileMakerPro, the human-machine interface of the system has been able to be
      improved easily. In addition, cooperation with HIS, RIS, and PACS could be
      constructed. Therefore, this original system would contribute to increasing the
      efficiency of radiological diagnosis.

PMID- 15148785
TI  - [Application of diffusion-weighted MR imaging to the diagnosis of bone
      metastasis: a fundamental study using rabbit bone tumor model].
AB  - PURPOSE: To evaluate diffusion-weighted magnetic resonance imaging(DW-MRI) for
      the diagnosis of bone metastasis, using rabbit bone tumor models. MATERIALS AND
      METHODS: Skeletal tumor lesions and inflammation were induced by the injection of
      VX-2 tumor cells in suspension and in croton oil, respectively, into the distal
      femur of Japanese white rabbits. Ten to fourteen days after the injection, MRI
      was performed under intravenous anesthesia. Single-shot echo planar DW images
      were obtained. After MRI, the diseased femurs were extirpated, histologically
      analyzed, and compared with DW images. The apparent diffusion coefficient(ADC)
      values for the different tissue regions were compared, and the relationships with
      histological measurements were examined. RESULTS: In the necrotic regions of
      intraskeletal tumors, ADC values were higher than those in regions with abundant
      viable tumor cells(p < 0.0001). In extraskeletal tumors, necrotic cells were
      numerous, and ADC values were similar to those in the intraskeletal necrotic
      tumors. Intraskeletal inflammatory lesions and normal bone marrow showed the
      highest and lowest ADC values, respectively(p < 0.0001). ADC values were
      negatively correlated with cell area density and the nuclear/cytoplasmic ratio.
      CONCLUSION: ADC values in various skeletal lesions correlated with histological
      features, suggesting the potential usefulness of ADC mapping in differentiating
      osteomyelitis from bone metastasis.

PMID- 15148787
TI  - [Usefulness of Cho/Cr ratio in proton MR spectroscopy for differentiating
      residual/recurrent glioma from non-neoplastic lesions].
AB  - PURPOSE: We evaluated the clinical usefulness of the Cho/Cr ratio of proton MR
      spectroscopy(1H-MRS) to differentiate residual/recurrent glioma from non
      neoplastic lesions. PATIENTS AND METHODS: 20 cases of glioma were involved in
      this study(astrocytoma grade I-II: 7, oligodendroglioma: 1, astrocytoma grade
      III: 2, glioblastoma: 10). Seven of the patients underwent surgical resection
      only, 4 underwent surgical resection and radiotherapy(40-60 Gy), and 9 underwent
      surgical resection and radiotherapy with concurrent chemotherapy(14-60 Gy). 1H
      MRS was performed on a 1.5 Tesla clinical MR unit using a 3D-chemical shift
      imaging sequence(1500 msec/270 msec/1 (TR/TE/excitations), and the Cho/Cr ratio
      was calculated in the voxel where neoplastic lesion was most suspected on MRI.
      The presence of lactate + lipid peak was also evaluated. All spectra were
      obtained after the contrast enhanced study. RESULTS: Cho/Cr ratios were
      significantly higher in cases of residual/recurrent tumors(mean +/- SD = 1.70 +/-
      0.96) than in non-neoplastic lesions(mean +/- SD = 1.04 +/- 1.16) (Mann-Whitney U
      test p = 0.047). If a Cho/Cr ratio of more than 1.5 was used as a marker of tumor
      presence, its sensitivity was 64%, specificity 83%, and accuracy 70%. One false
      positive case that of radiation necrosis whose spectrum showed a high Cho/Cr
      ratio with markedly elevated lactate + lipid peak. CONCLUSION: The Cho/Cr ratio
      of 1H-MRS provides additional information to MRI in differentiating
      residual/recurrent gliomas from non-neoplastic lesions.

PMID- 15148788
TI  - [Follow-up dynamic CT study for hypovascular nodules in patients with cirrhotic
      liver].
AB  - It is important to clarify the process by which hypovascular nodules progress to
      hypervascular hepatocellular carcinoma (HCC). In this study, we used dynamic
      computed tomography(CT) to retrospectively investigate serial changes in 24
      hypovascular nodules of 24 patients until they progressed to hypervascular HCC.
      The mean time to hypervascular transformation(THT) was 726 days, with a minimum
      of 208 days and maximum of 2,728 days. Mean nodular diameter at the final
      examination was 21.2 +/- 8.0 mm, and was significantly larger than that(11.4 +/-
      4.8 mm) at the initial time. THT was the shortest(463 days) in a group that had
      an initial nodular diameter larger than 15 mm. In a group with the low-iso-low
      contrast enhancement pattern, THT was 361 days, and was shorter than that in the
      other groups. In a group with the low-low-low contrast enhancement pattern,
      nodules containing fat were frequently detected(5 patients, 75%). In patients
      with HCC apart from the nodules, THT for the nodules was 464 days, shorter than
      that(767.5 days) in other patients. The findings suggest that hypovascular
      nodules larger than 15 mm in diameter with the low-iso-low contrast enhancement
      pattern and HCC progress to hypervascular HCC at an early stage.

PMID- 15148789
TI  - [Usefulness of 3D conformal radiation therapy for reduction of radiation-induced
      white matter injury].
AB  - PURPOSE: The usefulness of three-dimensional conformal radiation therapy(3DCRT)
      in decreasing radiation-induced white matter changes(WMC) was assessed. MATERIAL
      AND METHODS: Thirty-seven patients(age 5-77 years, mean 42 years; male/female =
      11/26) with primary intracranial tumors received 40 Gy or more, and were followed
      up with MRI for more than one year. Thirty-four patients underwent
      chemotherapy(with a platinum drug, 16; without a platinum drug, 18). Nineteen
      were treated with 3DCRT (radiation dose, range 60-64 Gy, mean 60.2 Gy; maximum
      width of radiation field, range 7-16 cm, mean 12.5 cm) and 18 were treated with
      non-3DCRT (radiation dose, range 40-62.4 Gy, mean 53.4 Gy; maximum width of
      radiation field, range 4-19 cm, mean 12.3 cm). RESULTS: WMC occurred in 37% of
      the 3DCRT group and 50% of the non-3DCRT group. Among the patients with WMC,
      Karnofsky performance scale(KPS) deteriorated in none of the 3DCRT group, whereas
      KPS deteriorated in 3 of 9 in the non-3DCRT group. All the patients with
      deterioration of KPS were at least 50 years of age. KPS did not strictly
      correlate with the severity of white matter changes on MRI. Chemotherapy with a
      platinum drug increased the incidence of WMC. Age(< 50 years vs. > or = 50
      years), gender, radiation technique(3DCRT vs. non-3DCRT), radiation dose(< 60 Gy
      vs. > or = 60 Gy), maximum field-size(< 12 cm vs. > or = 12 cm), and maximum
      boost-field size(< 10 cm vs. > or = 10 cm) were not relevant to the incidence and
      severity of WMC. CONCLUSION: Though 3DCRT did not decrease the incidence and
      severity of white matter change on MRI, it may be useful to preserve the KPS,
      especially for older patients.

PMID- 15148790
TI  - [Outcomes of radiation therapy for maxillary sinus carcinoma].
AB  - PURPOSE: We evaluated the outcome of radiation therapy for maxillary sinus
      carcinoma treated in our institution. MATERIALS AND METHODS: From 1984 to 2001,
      48 patients with maxillary sinus carcinoma were irradiated with or without
      chemotherapy and surgery. Patients ranged from 20-89 years of age (median, 68
      years) and included 29 men and 19 women. The clinical T factors for these
      patients, according to the UICC classification (1997), were T2(n = 2), T3(n =
      13), and T4(n = 29). Lymph node involvement was observed in 13 patients. The
      follow-upperiod ranged from 2.5 to 150 months (median, 25 months). The total
      radiotherapy dose ranged from 40 Gy to 72.8 Gy. Forty-three patients underwent
      surgery. Intra-arterial chemotherapy was delivered in 39 patients, and systemic
      chemotherapy was delivered in 7 patients. Fourteen patients were classified as
      "unresected" (radiation therapy with or without antrostomy), and 34 patients as
      "resected" (partial, total, or extended total maxillectomy with pre- or
      postoperativeirradiation). RESULTS: The 5-year overall survival rate(OS), cause
      specific survival rate(CSS), and local control rate(LC) of all patients were 52%,
      64%, and 75%, respectively. There was no significant difference between the
      "uaresected" and "resected" groups in OS, CSS, or LC. Local recurrence was
      observed in 12 patients. In the "resected" group, for local control, it was
      important to reduce viable tumor before maxillectomy. Preoperative > or = 60 Gy
      irradiation was considered to be effective to reduce tumor viability. CONCLUSION:
      There was no significant difference between the "unresected" and "resected"
      groups in OS, CSS, or LC. In the "resected" group, preoperative irradiation > or
      = 60 Gy was considered to be effective for local control. In radical treatment of
      maxillary sinus carcinoma, maxillectomy is not always necessary. Concurrent
      chemoradiation therapy with or without antrostomy is a reasonable treatment
      strategy.

PMID- 15148791
TI  - [Hypothyroidism after radiotherapy to the neck].
AB  - PURPOSE: The purpose of this study was to investigate the incidence and possible
      predictors of hypothyroidism after radiotherapy to the neck, focusing on
      radiation dose-volume factors. METHODS AND MATERIALS: Thyroid function was
      measured in 169 patients treated with radiation ports including the thyroid,
      between 1989 and 2000. Hypothyroidism was determined with an endpoint of elevated
      serum thyroid stimulating hormone(TSH) levels > 10.0 microU/ml. In 60 patients,
      radiation dose-volume factors were calculated; e.g., total volume of the thyroid,
      mean radiation dose to the thyroid, and %-volume of the thyroid which received
      radiation doses of no less than 10-70 Gy(V10-V70). The evaluated risk factors for
      hypothyroidism included these dose-volume factors, sex, age, primary disease,
      combined chemotherapy, and follow-up period. RESULTS: Hypothyroidism was detected
      in 33 (19.5%) of the 169 patients. None of them had clinical symptoms of
      hypothyroidism. V10, V20, and V30 seemed to be possible predictors of
      hypothyroidism and had a significant impact on the peak level of serum TSH.
      CONCLUSION: Radiation dose-volume factors of the thyroid seemed to correlate with
      the incidence of hypothyroidism, and V10, V20, and V30 had a significant impact
      on the peak level of serum TSH.

PMID- 15148792
TI  - [Survey of CT practice in Japan and collective effective dose estimation].
AB  - Computed tomography(CT) has been established as an important diagnostic tool in
      clinical medicine and has become a major source of medical exposure. A nationwide
      survey regarding CT examinations was carried out in Japan in 2000. CT units per
      million people in Japan numbered 87.8. The annual number of examinations was 0.1
      million in those 0-14 years old, 3.54 million for those 15 years old and above,
      and 3.65 million in total. Eighty percent of examinations for those 0-14 years
      old were examinations of the head, as were 40% for those 15 years old and above.
      The number of examinations per 1000 population was 290. The collective effective
      dose was 295 x 10(3) person.Sv, and the effective dose per caput was evaluated as
      2.3 mSv.

PMID- 15148793
TI  - [Fusion imaging of three-dimensional angiographies of arteries and veins around
      the stomach by multiphase fusion technique under single breath-hold using 16
      detector multislice CT].
AB  - Postcontrast CT scan using multislice CT was performed in 10 patients prior to
      laparoscopic gastric cancer surgery. Using 16-detector multislice CT, images were
      obtained at both arterial and venous phases under a single breath-hold. Three
      dimensional CT angiography at arterial and venous phases was respectively
      reconstructed using the volume-rendering technique and then fused. Multiphase
      fusion imaging was able to demonstrate clearly, simultaneously, and three
      dimensionally the gastric arteries and veins without a respiratory gap. In
      conclusion, multiphase fusion images were considered to be very useful for the
      intraoperative navigation of laparoscopic gastric cancer surgery.

PMID- 15148794
TI  - [Bioethics and leading therapeutics].

PMID- 15148796
TI  - [New monitoring method for the pudental nerve during surgery: cases of
      intraoperative monitoring for lumbo-sacral lipomeningocele].
AB  - We carried out intraoperative monitoring of the pudental nerve while separating
      vertebral spinal tumors from the spinal cord in five patients, including four
      infants. Although monitoring using a manometer or needle electrodes has been
      reported, monitoring done with disk electrodes to ascertain the compound muscle
      action potential (CMAP) of the external sphincter muscle has not been yet
      attempted. Prior to the surgical procedure, we locate a point suitable for CAMP
      recording of the muscle. In our recent study, we determined that maximum action
      potentials were recorded in the part with the greatest depth from the individual
      anal verge. Therefore, the depth of the anal canal was preoperatively measured
      for the manometry method, and sphincter electrodes currently on the market were
      refigured to suit the infant's anal canal. After the two procedures described
      above, we were able to preserve the pudental nerves intraoperatively. The
      postoperative neurological findings of all five patients were unchanged. We
      introduce here this new method of intraoperative monitoring for preserving the
      pudental nerve.

PMID- 15148795
TI  - [Evaluation of the contours and perianeurysmal environment of unruptured cerebral
      aneurysms, using three-dimensional magnetic resonance cisternogram].
AB  - To evaluate the anatomical relationship between cerebral aneurysm and the
      perianeurysmal environment within a cisternal space, the contours of an
      unruptured cerebral aneurysm and pericisternal structures were depicted on a
      three-dimensional (3D) MR cisternogram. By using perspective volume-rendering
      algorithm, the 3D MR cisternograms were reconstructed from the source axial
      volume data set obtained by the T2-weighted 3D fast spin-echo sequence. Those
      images were shown together with the coordinated 3D MR angiograms through similar
      visual projections, and then compared with the intraoperative findings. The outer
      wall configurations of cerebral aneurysms within the cisternal space were shown
      in conjunction with the accompanying surface veins, adjacent cranial nerves, dura
      mater and tentorial edge, cranial base bone, and surrounding pericisternal brain
      surfaces. With application of 3D MR cisternograms in the management of unruptured
      cerebral aneurysm, the anatomical relationship between the aneurysmal contours
      and the perianeurysmal environment could be evaluated the within the cisternal
      space. This might provide another clinical factor when considering the potential
      risk of growth, rupture, and symptomatic cranial nerve signs of an unruptured
      cerebral aneurysm.

PMID- 15148797
TI  - [Experience of treatment for blunt traumatic out-of-hospital cardiopulmonary
      arrest patients over 24 years: head injury v.s. non-head injury].
AB  - PURPOSE: We investigated blunt traumatic out-of-hospital cardiopulmonary arrest
      patients whether any clinical differences between with and without head injury
      existed or not. METHODS: A retrospective chart review of 332 blunt traumatic out
      of-hospital cardiopulmonary arrest cases that had been transported to our
      hospital between January 1980 and April 2003. They were divided into two groups,
      head injury (HI, n = 175) and non-head injury (NHI, n = 157). RESULTS: There were
      no significant differences between the groups with respect to sex, age, mechanism
      of injury, witnessed arrest, bystander cardiopulmonary arrest, value of
      hemoglobin, value of base excess, and electrocardiogram on arrival. Averaged
      total abbreviated injury scale in the HI was greater than in the NHI, however
      return of spontaneous circulation in the HI was more frequent than in the NHI.
      Survival discharge rate was under 2% and good recovery case was none in the two
      groups. CONCLUSIONS: Among lethal blunt traumatic injuries, there were no
      different backgrounds between with and without head injury. The return of
      spontaneous circulation in the blunt traumatic patients with head injury became
      higher than without head injury, however the outcomes were similarly extremely
      poor.

PMID- 15148799
TI  - [Evaluation of lumbar tap test combined with mean cerebral blood flow measurement
      and electroencephalographic topography on idiopathic normal pressure
      hydrocephalus patients].
AB  - PURPOSE: To improve the diagnostic precision of the lumbar tap test (LTT).
      SUBJECTS AND METHODS: Thirty one patients (mean age, 65.4 years; male to female
      ratio, 12:19) suspected of having idiopathic normal pressure hydrocephalus (INPH)
      were used in the study. They underwent LTT (20-30 ml of cerebrospinal fluid was
      drained through a puncture with a 18 G needle; evaluation within 3 days after
      LTT). Based on changes in symptoms after LTT, including dementia (evaluated
      according to the duration of time needed to accomplish No. 7 items in the N
      method psychofunction test) and gait disturbance (evaluated according to the
      duration and the number of steps needed to walk 4 m in a straight line), mean
      cerebral blood flow (mCBF) monitored with 133Xe-CT, and electroencephalographic
      topography (EEG-T). The patients were divided into symptom-improved [LTT (+)] and
      no change [LTT(-)] groups. Changing patterns of EEG-T and mCBF after LTT and the
      efficacy of V-P shunt at 1 month after shunt administration (effective: E; non
      effective: NE) were analyzed and compared. Changing patterns of EEG-T and mCBF
      after LTT were categorized as improvement of both parameters (type A), that of
      mCBF only (type B), that of EEG-T only (type C), and no change in either
      parameter (type D). RESULTS: (1) Twenty patients were classified as LTT(+) and
      eleven as LTT(-). (2) The false positive rate was 25% (5/20) for LTT(+); the
      false negative rate was 27.3% (3/11) for LTT (-). (3) In all the patients, in
      relation to changing patterns of EEG-T and mCBF, 100% of type A patients (9/9),
      75% of type B (6/8), 42.9% of type C (3/7), and 0% of type D (0/7) responded to
      shunting. (4) Increased rates (IR) of mCBF in 17 patients with improvement of
      mCBF were 24.2 +/- 10.6% in E patients and 8.9 +/- 5.2% in NE patients,
      demonstrating a significantly higher percentage in E patients (p < 0.005). The
      borderline of IR between E and NE was around 15%. CONCLUSION: (1) Although
      quantitative evaluation of symptoms (dementia and gait disturbance) before and
      after LTT, 27.3% of false negative and 25% of false positive were recognized. (2)
      According to changing patterns of EEG-T and mCBF after LTT, all type A patients
      responded to shunting (E), whereas type D patients were all categorized as NE.
      (3) When the IR of mCBF was 15% or more after LTT, such patients all responded to
      shunting. (4) The diagnostic precision of LTT in efficacy evaluation is improved
      when this test is combined with EEG-T and mCBF, in addition to quantitative
      evaluation of symptoms.

PMID- 15148798
TI  - [Simultaneous multiple hypertensive intracerebral hematoma].
AB  - Hypertensive intracerebral hemorrhage (HIH) occurring simultaneously in different
      locations is rare. We encountered 11 such cases between January 1990 and November
      2002. The diagnosis of all 11 cases was established by computed tomography, and
      the location of the hematomas was: cerebellum and basal ganglia in 5 cases, pons
      and basal ganglia in 4, and subcortex and basal ganglia in 2. Our patients were
      analyzed with respect to clinical characteristics, pathogenesis of multiple
      hematomas, and indication of operation. These patients represented 1% of all
      1,069 patients we encountered with HIH. As past history, there were no
      characteristic disorders except hypertension. There were no characteristic
      initial symptoms suggesting that hemorrhage had occurred simultaneously. Both
      supra- and infra-tentorial hematomas were observed in 80% of the patients, and
      the size of the multiple hematomas was proportional in principle. Cerebellar
      hematomas were often mild, and pontine hematomas were often severe. The outcome
      in those patients whose neurological grading was 1 to 3 was good with
      conservative therapy or surgical treatment. The severity, treatment methods, and
      outcomes in these patients were similar to those in patients with single HIH,
      which suggests only a slight influence of multiple lesions on outcome. As for the
      possible mechanism of simultaneous multiple hemorrhages, we speculated that
      bleeding occurred simultaneously in the different regions, or that the initial
      bleeding was followed after a short time by secondary bleeding due to high
      intracranial pressure and circulatory disturbance. In patients with cerebellar
      hematoma, initial symptoms suggested the development of secondary hemorrhage
      after primary hemorrhage. The surgical treatment for multiple hematomas should be
      determined by the location and maximum axis of the hematoma. We proposed that
      cerebellar hematomas should be removed if the supra-tentorial hematoma is small.

PMID- 15148800
TI  - [A case of multiple cerebral infarction accompanied by a cor triatriatum].
AB  - A cor triatriatum is a congenital malformation of the heart which, in almost all
      cases, is diagnosed in childhood, whereas adult cases are very rare. The
      hemodynamics of the cor triatriatum is similar to that of mitral stenosis, which
      sometimes, but rarely, causes embolism. We present a case of multiple cerebral
      infarctions accompanied with a cor triatriatum. A 57-year-old female suddenly
      displayed impaired consciousness and hemiparesis immediately after cranioplasty
      for another disease, and was diagnosed by a diffusion weighted MRI as having
      multiple infarctions. A transesophageal echocardiography detected a membrane
      like, echo-dense structure across the left atrium, suggesting a cor triatriatum.
      We suspect that her multiple infarctions were caused by embolism due to a cor
      triatriatum. Here, we discuss the relationship between her embolic stroke and the
      cor triatriatum, with references to literature on the subject.

PMID- 15148801
TI  - [Multiple recurrences of cerebellar hemangioblastoma after 20 years from initial
      total removal of the tumor].
AB  - Cerebellar hemangioblastoma develops alone or develops as part of von Hippel
      Lindau disease. Moreover, multiple hemangioblastomas are found in 10-15%. It was
      reported that some hemangioblastomas recur with multiple recurrence in long time
      follow-up period. A 51 years old male was referred to our hospital because of
      headache and found a cerebellar tumor which was totally removed and diagnosed as
      hemangioblastoma pathologically. He presented no deficit after first surgery, but
      he did not come our hospital. In May 2000, he was referred to our hospital
      because of headache again and found five cerebellar tumors on MRI. Angiography
      showed markedly tumor stain. Retinal and spinal lesions were not seen. Two of
      five tumors was removed. The remaining three small tumors were received gamma
      knife surgery. In December 2000, because of cyst enlargement, one tumor was
      removed and the cyst was opened. In June 2001, he presented right hearing
      disturbance due to enlargement of cerebellar pontine angle tumor. The tumor was
      removed after tumor embolization, but hearing disturbance and slight dizziness
      remained. The remaining 5 mm tumor is followed.

PMID- 15148802
TI  - [Single burr hole surgery for acute spontaneous subdural hematoma in the aged:
      patient reports of three cases].
AB  - The method of treatment for acute spontaneous subdural hematoma in aged patients
      is controversial. Three cases of acute spontaneous subdural hematoma in aged
      patients, treated by single burr hole drainage without irrigation, were reported.
      The first case, an 80-year-old male was admitted with complaints of headache and
      stupor without any history of head trauma. CT revealed a left subdural hematoma
      with mixed density. Intractable facial convulsion occurred three days after
      admission. Single burr hole drainage was performed to remove the hematoma, and
      facial convulsion disappeared one week after the surgery. The second case, a 70
      year-old male was admitted with complaints of consciousness disturbance without
      any history of head trauma. CT showed a right subdural hematoma with mixed
      density. The next day, he recovered consciousness and CT demonstrated shrinkage
      of the hematoma. However, his consciousness deteriorated again 11 days after
      admission, and CT revealed progression of the hematoma. We performed single burr
      hole drainage, and the next day, his neurological condition recovered. The third
      case, an 84-year-old female was admitted with complaints of consciousness
      disturbance without any history of head trauma. CT revealed a left subdural
      hematoma with mixed density. Single burr hole drainage was performed to remove
      the hematoma. She recovered completely and was discharged and return home 1 month
      after the surgery. Single burr hole drainage is less invasive than craniotomy.
      Our three cases indicate that this method may be one of the best methods for aged
      patients with acute spontaneous subdural hematoma which manifests mixed density
      in CT.

PMID- 15148803
TI  - [Intracranial metastasis of pituitary adenoma: a case report].
AB  - Growth hormone-secreting pituitary adenoma is usually benign, and distant
      metastases are extremely rare. A case of growth hormone-secreting pituitary
      adenoma with multiple dural metastases is reported. A 53-year-old male was
      initially admitted to our hospital complaining of visual loss, presenting a
      pituitary abnormal mass with suprasellar extension. At the initial surgery,
      transsphenoidal surgery was selected, and the histological finding was benign
      pituitary adenoma. Seven and 16 months after the initial surgery, second and
      third surgeries via a transcranium route were performed for recurrence of the
      pituitary tumor. Histological findings revealed an appearance similar to the
      initial tumor in both surgical specimens. After the third operation, radiation
      therapy (local irradiation: total; 44 Gy) was performed. Six years after the
      first surgery, three tumors were located in the right frontal, parietal convexity
      and cerebellar tentorium. The tumors were totally removed by 4th and 5th
      surgeries. Histological examination showed malignant transformation from the
      primary benign growth hormone-secreting pituitary adenoma, with dural metastasis.
      Immunohistochemical staining with MIB-1 antibody demonstrated a high index of 7%.
      The patient is still alive after more than one year since the diagnosis of
      distant metastasis. According to previous reviews, few patients have survived
      more than one year. We conclude patients with benign pituitary adenoma should be
      carefully followed up for fear of malignant transformation or dural metastasis.

PMID- 15148804
TI  - [Usefulness of diffusion-weighted magnetic resonance imaging in diagnosis and
      therapeutic strategy of deep cerebral venous thrombosis: a case report].
AB  - We present the usefulness of Diffusion-weighted magnetic resonance images (DWI)
      in diagnosis and therapeutic strategy of deep cerebral venous thrombosis (VT). We
      report a 37-year-old man who suffered general convulsion and deep coma. Magnetic
      resonance imaging (MRI) showed high intensity in the right caudate nuclei and
      bilateral thalamus on T2-weighted images. DWI showed slightly high intensity in
      the same area and apparent diffusion coefficient (ADC) is normal or slightly high
      (0.748-1.100 x 10(-3) mm2/s). Cerebral angiography showed occlusion of straight
      sinus from basal veins and internal cerebral veins bilaterally. We treated by
      anticoagulation, ventricle drainage, barubiturate and normothermia therapy with
      intracranial pressure (ICP) monitoring. We considered endovascular thrombolysis
      to be dangerous in this case because of hemorrhage and didn't it. ICP was more
      than 40 mmHg and consciousness was comatose in acute stage, however, ICP
      gradually got to be normal, consciousness became almost clear and he recovered.
      Follow-up Cerebral angiography showed recanalization of deep venous thrombosis.
      Follow-up MRI showed disappearance of high intensity in the right caudate nuclei
      and bilateral thalamus on T2-weighted images and DWI. In this case, we could
      predict reversible vasogenic edema by DWI and ADC in VT.

PMID- 15148805
TI  - [A case of arteriovenous malformation associated with moyamoya phenomenon].
AB  - A case with arteriovenous malformation (AVM) associated with moyamoya phenomenon
      is reported. The 44 year-old female patient was presented with headache and
      vomiting. Computed tomography (CT) scan showed intraventricular hemorrhage.
      Cerebral angiography showed right frontal AVM and severe stenosis of right
      internal carotid artery. The AVM was fed by typical moyamoya vessels, Heubner's
      artery, and external carotid artery (ECA). We tried to embolize a bleeding point,
      compartment attached to lateral ventricle, but we could not. So, we embolized
      feeders from ECA and sent the patient to radiosurgery. We discuss here treatment
      and etiology of such rare condition.

PMID- 15148807
TI  - [Letter about case of metastatic brain tumor with postoperative bleeding from the
      tumor following radiosurgery].

PMID- 15148806
TI  - [Microrecording: a guide to stereotactic brain operations].

PMID- 15148808
TI  - [Genesis and progression of ectopic hormone-producing tumors].

PMID- 15148810
TI  - [Etiology of ectopic hormone producing tumors].
AB  - Inappropriate secretion of peptide hormones and other associated proteins by
      tumors is the most common cause of paraneoplastic syndromes. Sensitive assay
      techniques have permitted detection of polypeptide hormone secretion by tumors
      even in the absence of clinically overt syndromes. Moreover, it has been
      demonstrated that most or all nonendocrine tissues produce small amounts of a
      variety of peptide hormones and hormone precursors. Nevertheless, the term
      ectopic hormone syndromes occurring with nonendocrine neoplasms is well
      established and widely used. We summarize etiology of 'classic' ectopic hormone
      producing tumors to help establish the diagnosis of paraneoplastic humoral
      syndromes.

PMID- 15148809
TI  - [Familial tumor syndrome and ectopic hormone-producing tumors].
AB  - It has been thought that endocrine tumors occurred through interactions of
      multiple environments factors and a personal genetic factor. A normal somatic
      cell having an intrinsic function is able to obtain the character of a malignant
      cell by influence of many factors. Several percent of all tumors have obvious
      familial aggregation. These entity are called familial cancer. Familial cancer
      syndrome is well defined for colorectal cancer and breast cancer, but an
      endocrine neoplasia is the one, too. Ectopic hormone producing tumors are kinds
      of endocrine tumors, and have the characteristics, which they generate in many
      organs multicentrically. The phenomena suggest that the patient with these
      disorders may possess strong genetic predisposition. Among endocrine neoplasia,
      multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2
      (MEN2), von Hippel-Lindau disease(VHL) are well defined genetic disorder with
      autosomal dominant inheritance, and the reliable genes were previously identified
      as MEN1, RET, and VHL, respectively. At this opportunity, we interpret for these
      three disorders.

PMID- 15148811
TI  - [Endocrine tumors and growth factors].
AB  - A number of studies have revealed that various growth factors are produced in the
      malignant progression of endocrine tumors. Growth factors, classified based on
      their signal transduction pathways, exert the functions by binding to cell
      surface specific receptors, and promote the growth of tumors by autocrine and
      paracrine mechanisms. Growth factors such as VEGF and bFGF are also detected in
      endocrine tumors, and play an important role in the growth and metastasis of
      tumors via induction of angiogenesis. In the signal transduction pathways growth
      factors activate various kinases such as mitogen-activated protein kinase and/or
      phosphatidylinositol 3-kinase/Akt. Signaling cross-talk of growth factors,
      cytokines and steroid hormones has been observed in various endocrine tumors.

PMID- 15148812
TI  - [Neuroendocrine tumors of the lung].
AB  - Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical
      carcinoid, intermediate-grade atypical carcinoid, and high-grade categories of
      large cell neuroendocrine carcinoma(LCNEC) and small cell carcinoma(SCLC). Large
      cell neuroendocrine carcinoma is a newly recognized clinicopathologic entity as
      the fourth category of neuroendocrine tumors of the lung. The most common
      disagreements of pathological diagnosis fall between LCNEC and SCLC. The clinical
      characteristics and optimal treatments for patients with LCNEC are not presently
      defined well. The prognosis of LCNEC is suggested to be poorer than that of other
      non-small cell lung cancers in the recent studies. It is not clear how these
      patients should be treated. Further collaborative accumulation of
      clinicopathological data is strongly required.

PMID- 15148814
TI  - [Alteration of the K-ras and p16/CDKN2 gene in endocrine pancreatic carcinomas].
AB  - There are many observation of genetic alterations in pancreatic carcinoma.
      Mutation of codon 12 of K-ras gene relating to cell growth signaling was reported
      as high as 90%, and p16/CDKN2 gene regulating cell cycle are frequently altered
      by point mutation, homozygous deletion, or methylation in pancreatic carcinoma.
      Mutations of K-ras and p16 gene in endocrine pancreatic carcinomas were reported
      15-58% in insulinomas or gastrinomas. The alterations of K-ras and p16 gene was
      detected early event of carcinogenesis, to detect of the alteration with high
      sensitivity in pancreatic juice and serum, therefore, these alterations are very
      important for the early diagnosis of endocrine pancreatic carcinomas.

PMID- 15148813
TI  - [The RET gene in multiple endocrine neoplasia type 2 (MEN 2)].
AB  - Multiple endocrine neoplasia types 2A and 2B(MEN 2A and MEN 2B), and familial
      medullary thyroid carcinoma(FMTC) are autosomal, dominantly inherited syndromes
      involving endocrine tumors. MEN 2A is characterized by medullary thyroid
      carcinoma(MTC), pheochromocytoma(pheo), and parathyroid hyperplasia; MEN 2B is
      characterized by MTC, pheo, mucosal ganglioneuroma, and marfanoid habitus.
      Affected individuals in FMTC families develop MTC without any other
      abnormalities. MEN 2A and MEN 2B and FMTC are caused by germline mutations in the
      RET proto-oncogene. To investigate the spectrum of RET mutations among Japanese
      patients, we analyzed the RET gene 118 patients with MEN 2 or FMTC.

PMID- 15148815
TI  - [Ectopic hormone-producing tumor].

PMID- 15148816
TI  - [Endocrine tumor of the uterine cervix].
AB  - Endocrine tumor of the uterine cervix is rare, as only nine cases have been
      reported as patients who troubled by the ectopically endocrine hormone. Five of
      these patients afflicted by ectopic ACTH secretion which caused Cushing's
      syndrome, two suffered by insulin which resulted hypoglycemia, one distressed by
      PTH, and the other troubled by G-CSF. Seven of the nine patients were diagnosed
      histologically as small cell carcinoma, which was famous for neuroendocrine
      tumor, high incidence of vascular invasion and lymph node involvement, clinical
      behavior of hematogenously dissemination, and poor prognosis. Age of six patients
      was less than 50 years old, and metastatic tumor was confirmed in six of the nine
      patients.

PMID- 15148817
TI  - [The diagnosis of pancreatic endocrine tumors].
AB  - The pancreatic endocrine tumors are uncommon neoplasms and are classified into
      non-functional and functional tumors. According to whether the secreted hormones
      are originated from pancreatic islet cells or not, the tumors are also classified
      into normotopic and ectopic tumors. Except for insulinoma, more than 60% of them
      reveal malignant behavior. The presence of endocrine tumor is diagnosed when
      patients develop a hormone-specific symptom, and the location of tumors are
      usually diagnosed by a combination of ultrasonography, computed tomography,
      magnetic resonance imaging and selective angiography. A somatostatin receptor
      scintigraphy is promising. Nevertheless, these examinations occasionally failed
      to precisely locate the tumors especially when they are very small and/or
      multiple. For such cases, both portal venous sampling and arterial provocation
      test are helpful.

PMID- 15148818
TI  - [Diagnosis and management of asymptomatic MEN 2 gene carriers].
AB  - RET genetic testing affords valid clinical strategies in the diagnosis and
      management of MEN 2. For at risk family members, the test provides accurate
      diagnosis of gene carriers and best chance of cure of medullary thyroid carcinoma
      by prophylactic total thyroidectomy. The test results, however, may have medical,
      psychological, ethical, and social effects on the individuals as well as their
      families, it is important for an individual to know the potential consequences
      and to give an informed consent before having the genetic test. Health care
      providers should make efforts to be aware of these potential effects and to
      support a tested individual throughout the entire screening process.

PMID- 15148819
TI  - [Pathology of adrenal incidentaloma].
AB  - Adrenal incidentaloma or incidentally detected adrenal mass has recently
      increased in number because of the recent advancement of radiological diagnostic
      means. The clinical management and histopathological diagnosis of the resected
      adrenal mass has therefore become increasingly important. When surgical
      pathologists evaluate a resected adrenal mass of the patients with adrenal
      incidentaloma, it is very important to evaluate the following pathological
      aspects; 1. the mass is malignant or not? and 2. the mass is of adrenocortical
      origin or not. We will describe these aspects regarding the pathology of adrenal
      incidentaloma in this review with emphasis on the three aspects above.

PMID- 15148821
TI  - [Hormone production and secretion in thyroid tumors].
AB  - Thyroid epithelial cells can be classified into 2 types according to embryonic
      origin, those of foregut endoderm (follicular cells) and those of neuroectodermal
      deviation (C cells) origin. The production of TG, T4, and T3 is frequently
      evident with the immunoperoxidase methods is nontoxic thyroid tumors derived from
      follicular cells. In contrast, medullary thyroid carcinoma originated from
      thyroid C cells produces and secretes calcitonin. Thyroid transcription factor-1
      (TTF-1) regulates the expression of all hormones produced in thyroid. In recent
      years, evidence has been accumulating for the existence of a tumor group with
      traits of both follicular and medullary carcinoma, designated as mixed follicular
      and medullary carcinoma.

PMID- 15148820
TI  - [Clinical aspect of adrenal incidentaloma].
AB  - Adrenal incidentaloma is defined as clinically inapparent adrenal mass identified
      at abdominal imagine undertaken for health screening or examination of unrelated
      diseases. Recent national Survey by Research Committee of Japanese Ministry of
      Health and Labor revealed 2,016 cases of adrenal incidentaloma in year 1999.
      Analysis of 2,626 cases including additional new cases indicate 51% was non
      functional adrenocortical adenoma, cortisol producing adenoma 8.9%,
      pheochromocytoma 8.5%, aldosteronoma 4.2%, adrenal cancer 1.4%. Cut of point for
      cancer was estimated at 5 cm. 1 mg dexamethasone test and circadian rhythm of
      cortisol secretion evaluation may be necessary for exclusion of clinically
      inapparent cortisol producing adrenal adenoma known as preclinical Cushing's
      syndrome. Clinical aspect and management of adrenal incidentaloma was briefly
      reviewed based on this national report.

PMID- 15148822
TI  - [Incidentaloma of the thyroid].
AB  - Thyroid incidentalomas are common, often less than 1.5 cm in size, and frequently
      benign. It is recommended that low-risk patients with incidentalomas be followed
      up ultrasonographically in 6 to 12 months and not be subjected to routine testing
      with ultrasonographically guided fine-needle aspiration biopsy (US-FNA). In
      patients who have nodules larger than 1.5 cm in size, a history of head and neck
      irradiation, a strong family history of thyroid carcinoma, or ultrasonographic
      findings that suggest malignancy, US-FNA should be done. A patient with
      hypercalcemia caused by ectopic production of parathyroid hormone in papillary
      thyroid carcinoma was reported. It is known that medullary thyroid carcinoma
      rarely shows production of adrenocorticotropic hormone or serotonin. However,
      ectopic hormone productive tumors in the thyroid are extremely rare.

PMID- 15148823
TI  - [Pathology of pituitary incidentaloma].
AB  - With advance of neuroimaging technics, incidentally discovered pituitary masses
      (pituitary incidentalomas) are recently increased. In autopsy cases, pituitary
      adenomas have been discovered at the rate of 1.5-27% (mean 10%). More than 80% of
      these adenomas were smaller than 3 mm. Adenomas larger than 10 mm were extremely
      rare. Histologically autopsy adenomas were mostly PRL cell adenomas (PRLomas) and
      gonadotroph adenomas. Histology of autopsy PRLomas was different from that of
      surgically resected PRLomas. Clinically discovered pituitary incidentalomas
      include pituitary adenomas, Rathke's cleft cysts, and craniopharyngiomas. Most of
      incidental adenomas were histologically gonadotroph adenomas in our materials.
      Perphaps, autopsy adenomas may not grow to the clinically found incidentalomas.

PMID- 15148824
TI  - [Clinical aspects of pituitary incidentalomas].
AB  - The development of computed tomography(CT) and magnetic resonance imaging (MRI)
      has resulted in the discovery of unsuspected endocrinologically silent pituitary
      masses(pituitary incidentalomas). The management of these pituitary
      incidentalomas is controversial. Some lesions may increase in size, compress
      optic chiasm while others will remain unchanged in size. Five hundred and six
      patients with pituitary incidentalomas were obtained by questionnaire from March
      1999 to May 2000 under the auspices of the Ministry of Health, Labor and Welfare
      in Japan. In thirty-three patients with pituitary incidentalomas (13.3%)
      developed tumor enlargement during the mean follow-up period of 45.5 months. Of
      115 estimated non-functioning adenomas, 23(20.0%) tumor increased during mean
      follow up period of 50.7 months (range 10 to 173 months), while 5(5.4%) of 94
      estimated Rathke's cysts increased in size during follow up. Pituitary apoplexy
      was occurred in one patient of 248 patients (0.4%). Pituitary incidentalomas
      usually follow a benign course. Transsphenoidal adenectomy is indicated for a
      solid mass attached to optic chiasma. For other patients, MRI every 6 months for
      the first 2 years, and then yearly may be recommended.

PMID- 15148825
TI  - [Ectopic ACTH syndrome].
AB  - Although the clinical and biochemical discrimination of true Cushing syndrome
      from the Cushing phenotype is sometime difficult, four diagnostic studies are
      currently used: late-night serum and salivary cortisol level, urine free cortisol
      level, low-dose dexamethasone suppression, and the dexamethasone-CRH test. Using
      these tests, 90% of patients with Cushing syndrome are diagnosed. Once the
      diagnosis of the Cushing syndrome is firmly established, the next step is
      differential diagnosis of the subtype. Furthermore, the differentiation of
      pituitary and ectopic ACTH-dependent Cushing syndrome should be carried out using
      measurement of ACTH. Finally, bilateral petrosal sinus sampling for ACTH with CRH
      administration might be a powerful tool for a diagnosis for ectopic ACTH
      syndrome. A variety of benign and malignant tumors of non-pituitary tissues have
      been associated with the ectopic ACTH syndrome. The tumors most commonly
      associated with ACTH syndrome arise from neuroendocrine tissues, however, the
      pathogenesis of the ectopic ACTH syndrome remains unknown.

PMID- 15148826
TI  - [Pituitary tumors].
AB  - Pituitary adenomas have been reported to be the most common benign intracranial
      neoplasms. Recent radiological advancement has resulted in incidental diagnosis
      of pituitary tumors such as pituitary adenomas and Rathke's cleft cysts. The most
      common location of pituitary adenomas is intrasellar region with or without
      suprasellar extension. Pituitary tumors in unusual site, however, have been
      reported previously, including the sphenoid sinus, suprasellar region, clivus,
      nasal cavity, or something like that. The sources of ectopic pituitary tumors
      have been thought to be migration of pituitary cells in pituitary adenomas and of
      squamous epithelial cell remnants of the obliterated craniopharyngeal canal in
      craniopharyngiomas. We describe ectopic pituitary tumors and recent knowledge of
      etiology and pathology of pituitary tumors. Furthermore, we mention recent
      advancement of endonasal transsphenoidal surgery to treat pituitary tumors.

PMID- 15148827
TI  - [Multiple endocrine neoplasia].
AB  - A 69-year-old female having a large left adrenal mass and a nodular lesion in
      thyroid gland was admitted to the hospital. Endocrinologically she showed high
      levels of plasma ACTH and cortisol, which were not suppressed by high dose
      dexamethasone, elevated serum parathyroid hormone and markedly increased daily
      urinary excretion of catecholamines. She died of sepsis, and postmortem
      examination was performed. A left adrenal pheochromocytoma, which was
      immunohistochemically proven to be ACTH producing, a papillary thyroid carcinoma
      and parathyroid adenomas were found. To our knowledge this is the first report of
      coexistence of these three endocrine tumors in a single patient.

PMID- 15148828
TI  - [A case of MEN IIA variant associated with ectopic ACTH production and mammary
      carcinoma].
AB  - A 69-year-old house wife admitted to our hospital with complaints of fever,
      drowsiness, watery diarrhea and uncontrolled blood sugar level. She had been
      operated for the right mammary carcinoma 11 years ago. Left adrenal mass and
      nodules in the thyroid gland were discovered by CT and hypersecretion of
      adrenocortical hormone, catecholamine and PTH as well as ectopic ACTH production
      were indicated endocrinologically. Autopsy and histopathological examination
      revealed left adrenal pheochromecytoma associated with bilateral adrenocortical
      hypertrophy, adenomas in 2 of 5 parathyroid glands and papillary thyroid
      carcinoma with adenomatous goiter. Ectopic ACTH production was identified
      immunohistochemically in the pheochromecytoma. This case is a rare variant of non
      familial MEN (multiple endocrine neoplasm) type IIA with ectopic ACTH production
      and metachronous mammary carcinoma.

PMID- 15148829
TI  - [Ovarian neuroendocrine carcinoma associated with mucinous carcinoma and
      teratoma].
AB  - We experienced two rare case of ovarian neuroendocrine carcinoma (NEC); case 1,
      NEC associated with mucinous adenocarcinoma and dermoid cyst; case 2, NEC with
      mucinous cystadenoma. The former patient was not treated with chemotherapeutic
      therapy for her own initiative and died of the tumor extent ten months after
      surgery. The latter patient has taken an uneventful clinical course for ten years
      after surgery with chemotherapy. To our knowledge, there have been limited
      documents regarding ovarian NEC to date. No proper subclassification is not
      assigned to NEC in the current WHO classification of ovarian tumors. According to
      the certain investigators, the postoperative survival term of ovarian NEC
      considerably differs. The therapeutic protocols including chemotherapy and
      irradiation have not been established yet. In most ovarian NECs, histogenesis is
      considered to be associated with mucinous or teratoma tumor which coexists with
      NEC.

PMID- 15148830
TI  - [Undifferentiated carcinoma(endocrine cell carcinoma) of the colon].
AB  - Recently, several cases of undifferentiated carcinoma and endocrine cell
      carcinoma are reported in the Japanese literature. In some reports, it is seemed
      to be confused in differentiating the diagnosis of these carcinomas, and
      considered that these carcinomas are in the same entity. When undifferentiated
      carcinoma of the large intestine is indicated, aggressive exploration such as
      immunohistochemical staining entertaining a possible existence of endocrine cell
      carcinoma is essential. Both undifferentiated carcinoma and endocrine cell
      carcinoma have the least favorable prognosis and effective multimodal therapy,
      including operation and chemoradiotherapy should be established.

PMID- 15148832
TI  - [Novel treatment with oncolytic herpes simplex virus, 'HF10' against breast
      cancer].
AB  - An oncolytic herpes simplex virus type 1 mutant, named HF10, has been isolated
      and evaluated for anti-tumor efficacy in syngeneic immuno-competent mouse models.
      We have found that the mutant virus can very effectively treat cancer, and that
      all of survived mice acquire resistance to rechallenge of the tumor cells. Since
      a number of studies have shown that HF10 is effective and safe for use in
      localized or peritoneally disseminated malignant tumors of non-neuronal origin,
      phase I/II clinical trials using HF10 have been initiated for patients with
      metastatic breast cancer. Preliminary data from the clinical trials are
      encouraging.

PMID- 15148831
TI  - [Ectopic hormone-producing tumors--research and clinics].
AB  - Recent progress in endocrinology, cytokine research, and oncology has provided
      new information for further understanding of ectopic hormone-producing tumors.
      The mechanisms responsible for this morbidity need further investigations to
      clarify the neuroendocrine nature of tumor cells. Meanwhile, a common hormonal
      substance produced by a specific tumor could serve as a specific tumor marker for
      the tumor, as is the case of ProGRP for small cell lung cancer. The development
      of drugs for ectopic hormonal syndrome might be a good lesson of the molecular
      targeting for hormone signaling pathways. It is reasonable to postulate that the
      clinical entities covered by the term 'ectopic humoral syndrome' will be
      increasing.

PMID- 15148834
TI  - Why should I ventilate my patient with kyphoscoliosis?

PMID- 15148833
TI  - [CHARM study--new strategy for the treatment of heart failure].
AB  - CHARM (candesartan in heart failure assessment of reduction in mortality and
      morbidity) is the largest trial program in chronic heart failure. To elucidate
      the effect of candesartan on various symptomatic chronic heart failure, the
      randomization protocol was used in 3 separate trial arms: 2028 with LVEF < 40%
      who could not tolerate ACE inhibitors; 2548 with LVEF < 40% who already were
      taking ACE inhibitor; and 3023 with LVEF > 40%. The overall mortality benefit of
      the candesartan was better than placebo. In the 2 trial arms that included
      patients with LVEF < 40%, incidence of the mortality and hospitalization was
      significantly lower with candesartan than with placebo. It may be the new
      evidence of angiotensin receptor blocker on 3 other types of heart failure.

PMID- 15148835
TI  - Microalbuminuria in chronic obstructive pulmonary disease.
AB  - BACKGROUND: In this study, the presence of microalbuminuria in patients with
      chronic obstructive pulmonary disease (COPD) in whom no proteinuria was
      determined by conventional methods, has been studied taking into account the
      possible relationship between microalbuminuria and respiratory parameters and
      their predictive role on mortality. METHODS: Twenty-five cases with COPD who had
      been hospitalized because of an acute exacerbation and 25 healthy age and sex
      matched volunteers were included in the study. Microalbuminuria measurement,
      arterial blood gas analysis, and forced expiratory volume in one second (FEV1),
      forced vital capacity (FVC) measurements were performed in the COPD group at the
      beginning of hospitalisation (admission) and after therapy for an average period
      of 14 +/- 6 days when they were stable at the time of discharge (discharge).
      Urinary albumin/creatinine (a/c) ratio > or = 2.5 mg/mmol was accepted as
      microalbuminuria. RESULTS: Microalbuminuria was detected in 14 (56%) subjects at
      admission and in 7 (28%) subjects at discharge in the COPD group and in 1 (4%)
      subject in the control group. There were statistically significant differences
      among these groups (admission-control p < 0.001, discharge-control p = 0.023,
      admission-discharge p = 0.016). In COPD group, mean a/c ratio was 3.9 +/- 3.8 at
      the time of admission, 1.7 +/- 1.9 at discharge and 0.5 +/- 0.5 mg/mmol in the
      control group. There were statistically significant differences among these
      groups (admission-control p < 0.001, discharge-control p = 0.029, admission
      discharge p = 0.002). In the COPD group there were negative correlation between
      the microalbuminuria values at admission and arterial pO2 and oxygen saturation
      (p = 0.031, r = -0.433 and p = 0.002, r = -0.596 respectively). There were no
      relation between the microalbuminuria values and age, arterial pH, pCO2, FEV1
      percent predicted, FVC percent predicted and FEV1/FVC. There were no
      statistically significant differences between the subjects with or without
      microalbuminuria according to the median survival time. CONCLUSIONS: In a quite
      large number of patients with COPD in whom no proteinuria were determined by
      conventional methods, especially at the time of exacerbation, microalbuminuria
      could be seen. Microalbuminuria was related with hypoxemia but has no predictive
      role on mortality.

PMID- 15148837
TI  - Nocturnal mechanical ventilation improves exercise capacity in kyphoscoliotic
      patients with respiratory impairment.
AB  - BACKGROUND: Patients with severe kyphoscoliosis, with or without stable
      respiratory failure, frequently experience oxyhaemoglobin desaturation during
      sleep, exercise, or both. Nasal Intermittent Positive Pressure Ventilation
      (NIPPV) applied during sleep has been demonstrated to be able to control
      nocturnal desaturations and also improve diurnal respiratory failure, if this is
      present, in this group of patients. The aim of this study was to evaluate the
      effect of a seven-day treatment with nocturnal NIPPV on exercise tolerance in a
      group of 6 patients with severe kyphoscoliosis and significant nocturnal and
      exercise-induced oxyhaemoglobin desaturation. METHODS: NIPPV was applied each
      night for a week by means of a volume cycled pressure ventilator set in
      assisted/controlled mode. In each patient lung function, daytime arterial blood
      gas analysis, overnight non invasive recording of arterial saturation, and 6
      minutes walking test were carried out initially and at the end of the NIPPV
      course. RESULTS: During nocturnal NIPPV, as compared to baseline, the percent of
      night time spent below 90% of oxyhaemoglobin saturation significantly fell from
      20 +/- 12.8 to 2.3 +/- 1.9 (Student t-test: p = 0.017). The 6-minute walking
      distance significantly increased from 244.7 +/- 132.2 to 340 +/- 122.3 m (p =
      0.0097). Spirometry, daytime arterial blood gas analysis, and exercise-induced
      oxyhaemoglobin desaturation were unaffected by treatment. CONCLUSION: A one-week
      course of treatment with nocturnal NIPPV improves exercise capacity in patients
      with severe kyphoscoliosis.

PMID- 15148836
TI  - Markers of inflammation and oxidative stress during lower respiratory tract
      infections in COPD patients.
AB  - BACKGROUND: Lower respiratory tract infections (LRTI) occur frequently in
      patients with Chronic Obstructive Pulmonary Disease (COPD), and are a major cause
      of morbidity, mortality and health care utilization. The aim of this study was to
      investigate if non- or less invasive markers of inflammation and oxidative stress
      can predict the course of the infections. METHODS: Twenty-five COPD patients who
      were admitted to hospital with a LRTI were included. Within 24 hours after
      admittance, spirometry (FEV1, FVC, MEF50), measurement of hydrogen peroxide
      (H2O2) in exhaled breath condensate (EBC), symptom scores and analyses of ESR,
      CRP, ECP, and MPO in serum were performed. All patients were treated with
      intravenous dexamethasone, nebulised salbutamol/ipratropium and, if needed,
      antibiotics. The tests were repeated at day 2, 3, 7 and 30. RESULTS: Complete
      data of the first four visits were collected in 19 patients. The H2O2
      concentration and spirometry parameters did not change significantly during the
      study period. CRP, ESR and MPO levels decreased significantly during treatment,
      while the other serum inflammatory parameters did not change. There were no
      significant correlations between H2O2 concentration, spirometry and serum
      inflammatory parameters. CONCLUSIONS: In conclusion, this study showed no
      significant changes in H2O2 concentration in EBC, or spirometry during treatment
      of a LRTI in COPD patients. In contrast, several serum inflammatory markers did
      decrease during hospitalization, thus providing a simple tool to monitor
      exacerbations.

PMID- 15148838
TI  - Intratumoral gene therapy for non-small cell lung cancer: current status and
      future directions.
AB  - Major advances in the field of molecular genetics and cancer biology have allowed
      for the development of rationally designed anti-cancer strategies. When genetic
      material (DNA or RNA) is used for this purpose, this approach is called gene
      therapy. Cancer cells are remarkably sensitive to the inhibition of activated
      oncogenes or replacement of lost tumor suppressor gene (TSG) function.
      Replacement of lost TSG p53 function has been achieved by the use of recombinant
      adenoviral vectors (rAdp53) that carry an expression cassette for this gene. Non
      small cell lung cancer has been the subject of early clinical trials in which
      intratumoral injection of rAdp53 has been performed by transthoracic CT-guided
      injection or bronchoscopy. Gene transfer and p53 transgene expression have been
      documented in injected tumors as well as the safety and feasibility of this type
      of gene therapy. Tumor regression has been reported in rAdp53-injected lesions,
      either alone or in combination with systemic chemotherapy. Randomized controlled
      studies as well as clear demonstrations of clinical benefit are missing at
      present. The results of ongoing studies will allow a verdict on the future of
      first generation rAdp53 gene therapy. For the whole of the field of gene therapy
      the advent of more efficient and safe gene transfer technology will determine the
      speed by which this innovative therapeutic modality will meet with clinical
      success.

PMID- 15148839
TI  - Recent insights into the relationship between airway inflammation and asthma.
AB  - There have been important recent advances in our understanding of the
      relationship between eosinophilic airway inflammation and airway dysfunction.
      Observational studies have shown that eosinophilic airway inflammation is not
      always present in asthma nor is it an exclusive feature of asthma. Its presence
      seems to be more closely linked to the presence of corticosteroid responsive
      airways disease and the occurrence of severe exacerbations than the presence of
      symptoms or the extent of airway dysfunction--indeed recent evidence suggests
      that in asthma these features may be more closely linked to the site of
      localisation of mast cells in the airway wall. One implication of this new
      understanding of the significance of eosinophilic airway inflammation is that it
      predicts that measuring airway inflammation might provide information that it is
      not readily available from a more traditional clinical assessment, and that
      patients might do better if this information is available. Recent studies support
      this view, showing a marked reduction in asthma exacerbation in patients with
      moderate to severe disease who are managed with reference to markers of airway
      inflammation as well as symptoms and simple tests of airway function. The
      development of new agents that have the potential to modulate specific aspects of
      airway inflammation, together with refinements in non-invasive techniques to
      assess the efficacy of these agents offers the prospect of further refining our
      understanding of the role of this aspect of the inflammatory response in asthma
      and other airway diseases.

PMID- 15148840
TI  - Muscle retraining in ICU patients.
AB  - The general aim of an ICU respiratory rehabilitation programme is to improve the
      patient's measured quality of life. It can be done by applying advanced
      therapeutic modalities in order to improve the remaining functions and to
      decrease the patient's dependency as well as the risks associated with an ICU
      admission. A number of physiological changes involve all the body systems as a
      consequence of a bed-rest period and play an important role in the weaning
      failure of ventilated patients. Inactivity muscle mass declines from the first
      week of ICU admission, as well as the muscle's ability to perform aerobic
      exercise. The respiratory muscles strength and endurance decreases, also the
      ventilatory pump and the cardiovascular response to exercise may be alterated.
      Disorientation, and disfunction of the Central Nervous System may occur. The aim
      of this review is to analyse the usefulness of skeletal and respiratory muscle
      training in improving strength, endurance and decreasing dyspnea at rest and
      during exercise and the role of rehabilitation in obtaining maximal functional
      capacity of ICU patients.

PMID- 15148841
TI  - Pulmonary artery leiomyosarcoma with thyroid metastases.
AB  - Primary pulmonary artery sarcomas are uncommon and usually fatal tumours. The
      diagnosis of these tumours is delayed in most cases as they are mistaken for
      pulmonary thromboembolism. We present a fatal case of a woman referred to us five
      months after a primary diagnosis of pulmonary thromboembolism, due to an increase
      in dyspnea and presence of hemoptysis despite having undergone anticoagulant
      treatment. On the basis of the findings obtained by computed tomography,
      echocardiogram and MRI, a mass arising from the pulmonary trunk was evidenced,
      that suggested other diagnostic hypotheses. The worsening of patient's conditions
      did not allow an endovascular catheter biopsy and diagnosis was made at autopsy.
      The mass was a leiomyosarcoma of the pulmonary artery with thyroid metastases,
      which is an uncommon findings.

PMID- 15148842
TI  - Management of purulent pericarditis.
AB  - A 50 year old man was admitted to ICU due to purulent pericarditis, purulent
      inflammation of the soft tissue of the neck, purulent mediastinitis and
      pneumonia. Subxyphoid periocardiotomy followed by the insertion of a drain into
      the pericardial space was performed. Four other drains were also inserted to
      drain purulent fluid from the neck (two drains) and mediastinum (two drains).
      During the surgical procedure, 700 ml of purulent pericardial fluid from the
      pericardial sac and 200 ml of purulent fluid from the mediastinum were drained.
      Antibiotic therapy was started upon admission to the hospital. Streptococcus
      species, Acinetobacter baumani and Enterococcus casseliflavus were cultured.
      Antibiotic therapy was adjusted to the results of the antibiogram. Despite
      revised antibiotic therapy, daily drainage from the pericardium--during several
      days after surgery--was around 200 ml. Due to the huge purulent pericardial
      drainage streptokinase, delivered directly into pericardial space, was given. The
      clinical effect of intrapericardial streptokinase administration was excellent.
      After 17 days drainage of purulent pericardial fluid was not observed. No
      clinical signs and symptoms of constrictive pericarditis developed. Repeated
      echocardiography examinations showed no signs of constrictive pericarditis and no
      pericardial fluid. The patient was discharged in good general condition.

PMID- 15148844
TI  - The role of nutritional status in the global assessment of severe COPD patients.

PMID- 15148843
TI  - A survey on policies of smoking control in Italian hospitals.
AB  - BACKGROUND: In Italy National regulations forbidding smoking inside hospitals
      have existed since 1975. Current International medical standards for staff
      include refraining from smoking as an intervention of health education aimed at
      promoting healthy lifestyles as well as reinforcing smoking cessation advice,
      which staff should give patients. According to a National survey 33.3% of staff
      are active smokers and up to 80% of them admit to smoking in the workplace. This
      study was aimed at asking the hospital administrative authorities about the
      current situation of smoking control, according to their experience and about
      activities and policies they think could be effective in implementing smoking
      control. METHODS: As a part of a European survey, financed by the EC, 217
      questionnaires were sent by mail to the General Managers of various hospitals in
      Italy, selected at random. The letter introducing the questionnaire was also
      signed by the unit of smoking control of the National Institute of Health (Rome).
      RESULTS: Out of the 217 questionnaires sent (56.8% in Northern Italy, 19.8% in
      Central Italy, 23.4% in Southern Italy), 85 (39.2%) were returned, 56.5% from
      Northern Italy, 22.3% from Central Italy, 21.2% from Southern Italy. Even if a
      smoking control policy is reported by the 82% of our sample, only 37.3% reported
      a complete ban of smoking. In 72% of hospitals there are no areas designated for
      smokers; only 51.3% provide help for smoking cessation and 83.2% report that no
      financial support is given to this policy. When asked about a point for smoking
      control the majority (72.9%) think of education of staff and half of the sample
      of reinforcing controls and repression as well as free smoking cessation
      treatments. Finally, when evaluation of compliance to existing rules is asked an
      insufficient or absent compliance is reported in 25.4% and the majority (50.7%)
      reported no smoking cessation clinic or service inside. Due to the low redemption
      rate, our sample cannot be considered as representative of the national hospital
      network. However, considering that only managers referring a good or sufficient
      smoking control have probably answered our questionnaire, we can conclude that
      the situation enlightened by our sample could be worse but not better in reality.
      CONCLUSIONS: In Italy the control of smoking in hospitals is far from reached. An
      implementation of smoking control needs support for cultural changes as well as a
      comprehensive policy towards smoking staff.

PMID- 15148845
TI  - Lung volume reduction surgery: results of controlled studies. The Italian
      experience.

PMID- 15148846
TI  - Volume-reducing surgery for emphysema: findings in earlier uncontrolled studies.

PMID- 15148847
TI  - Appetite stimulants and anabolic hormones.

PMID- 15148849
TI  - Home based rehabilitation for patients with COPD. Is it equally effective as
      compared to outpatient rehabilitation?

PMID- 15148848
TI  - Dyspnea relief.

PMID- 15148850
TI  - Biology of muscle impairment in COPD.

PMID- 15148851
TI  - Therapist driven protocols.

PMID- 15148852
TI  - Disability and health.

PMID- 15148854
TI  - Adolescents with Down syndrome.
AB  - Adolescence is a period of transition that can create stress for both adolescents
      and parents. Adolescents with Down syndrome (DS) go through the same stages as
      other adolescents, but due to lack of cognitive and behavioral factors they and
      their parents may find this period particularly challenging. This paper reviews
      several studies, especially from the United Kingdom, of groups of adolescents
      with Down syndrome and their controls followed from childhood, through
      adolescence into adulthood. There are special medical problems for this
      population that require annual medical examinations and surveillance, but the
      focus has shifted from health problems to social maturation, developing
      independence, and transition from school to employment or work activity. Medical
      transition from a pediatric to family physician provider is mentioned with
      recommendations as to how that transition can be made as smooth as possible.

PMID- 15148853
TI  - Rett syndrome management with Snoezelen or controlled multi-sensory stimulation.
      A review.
AB  - Rett syndrome is a neurological disorder resulting from an X-linked dominant
      mutation. It is characterized by a variety of physical and perceptual
      disabilities, resulting in a need for constant therapy programs to be
      administered on a regular basis throughout life. Resistance to physical activity
      has driven the authors in a search for new intervention techniques which might
      improve the ability to cope while reducing difficulty in handling an external
      physical facilitator. Snoezelen, or multi-sensory environment, can provide a
      soothing environment appealing to the child or adolescent with Rett syndrome
      while at the same time improving physical abilities. The article reviews Rett
      syndrome typical phenotype and suggests suitable activities that might take place
      in the multi-sensory environment.

PMID- 15148855
TI  - Adolescence, chronic illness and disability.
AB  - The prevalence of chronic illness or disability in adolescence has increased in
      recent years. In the past, children with certain chronic diseases did not reach
      adolescence, but over the last decade the survival rate has increased manyfold.
      The old morbidity (infectious disease, poor housing, poverty, lack of
      immunisation) has been exchanged with a new morbidity of adolescence, where a
      longer life expectancy is followed by an increase in lifelong disability. This
      review discusses issues concerned with the definition of disability in
      adolescence, reviews prevalence studies in several countries, the causes of
      disability, disparities, access and expenditure of health care, psychosocial
      aspects, and how to promote better outcomes.

PMID- 15148856
TI  - Childhood asthma management and control. Analysis of the Student Lung Health
      Survey (SLHS) database, Canada 1996.
AB  - The objective of this study was to estimate the severity of childhood asthma in
      Canada, identify the effects of asthma interventions in different target groups,
      and to profile asthma management and control practices by geographic area, sex,
      age, and severity groups. METHODS: The SLHS was conducted as a stratified and
      multi-staged cluster survey across Canada in 1996. It included a total of 136
      public, private and separate schools in nine health units (Prince Edward Island,
      Halifax, Sherbrooke, Kingston, Guelph, Winnipeg, Saskatoon, Edmonton, and
      Kelowna). The target study population was schoolchildren aged 5 to 19 years.
      Descriptive analyses were used to calculate the severity of childhood asthma for
      the different groups. Logistic regression was then employed to measure the
      quality of asthma intervention and control. Multivariate logistic regression was
      also used to compare the severity and treatment of asthma with age, sex and
      lifestyle, living and housing conditions. Using existing Clinical Practice
      Guidelines as a reference, the study also evaluated the effectiveness of
      interventions such as treatment, and asthmatic education. RESULTS: Based on the
      Canadian Consensus Recommendations of definition of asthma control, among all 5
      19 years old students, 39.9% were well controlled, 33.8% were acceptably
      controlled and 26.3% were poor controlled. The rates of intermittent and mild
      asthma were 44.8% and 11.6% compared with moderate (15.3%) and severe (0.9%).
      Students with asthma reported receiving more advantaged information from a
      demonstration of inhaler users (OR = 7.51, 95% CI = 5.65-8.94), during a medical
      visits (OR = 6.33, 95% CI = 5.11-7.83), from the pamphlet/brochures (OR = 6.22,
      95% CI = 5.05-7.76) or from a demonstration of the correct use of medicine (OR =
      5.62, 95% CI = 4.62-6.82). More students visited a family doctor (40.3%, OR =
      5.52, 95% CI = 4.95-6.64) and medical specialists (31.0%, OR = 3.69, 95% CI =
      2.58-4.78) than other specialist when they had respiratory problems. CONCLUSIONS:
      The results of the SLHS study demonstrated variations in the management and
      control of childhood asthma across Canada. The interventions and the practice
      guidelines for asthma control are useful for preventing and controlling asthma.
      These findings provide indications of interventions that are being used for the
      control of asthma in Canada.

PMID- 15148857
TI  - Blood phenylalanine control in adolescents with phenylketonuria.
AB  - In order to determine the degree of compliance with dietary treatment in
      adolescents with phenylketonuria (PKU) we have analysed blood phenylalanine (phe)
      results in 75 patients (42 male) aged between 10 and 20 years. We compared these
      results with the upper limit for blood phe and the blood sampling frequency as
      recommended by the United Kingdom's National Society for Phenylketonuria
      (NSPKU(UK)). The blood phe increased with age from a mean (1SD) of 0.51 mmol/l
      (0.19) at 10 years to 0.98 mmol/l (0.30) by 20 years. A mean of 17% (24) of
      samples were above the recommended range at 10 years, but this had increased to a
      mean of 75% (33) by 20 yrs. The frequency of blood sampling fell from a mean of
      83% (32) of that recommended to under 51% (37) by 20 years. Control was not
      significantly better in females compared with males. We conclude that although
      compliance with treatment in PKU is acceptable for most patients at 10 years this
      is not the case by late adolescents and early adulthood.

PMID- 15148859
TI  - Refeeding problems in a severe anorexia nervosa case.
AB  - Anorexia Nervosa (AN) is an eating disorder of puberty or adolescence. It is
      characterized by self-induced weight loss; various psychological disturbances
      including distorted body image, fear of obesity, active pursuit of thinness and
      loss of recognition of a number of body enteroreceptive sensations; and secondary
      physiological abnormalities. The treatment of AN includes individual
      psychotherapy, family therapy, and nutritional rehabilitation. Hospital treatment
      is required when the patient's medical condition is in danger due to hypovolemia
      or hypotension. If cardiac arrhythmias occur without electrolyte disturbances or
      if oral therapy fails, nutrition should be repleted by the safest method
      available. This can be done by nasogastric tube or intravenous hyperalimentation.
      The management of AN is challenging, because the treatment process and
      anticipated outcome is in direct conflict with the sufferer's own wishes. A
      comprehensive treatment plan including both psychiatric and medical approaches is
      necessary. We report a severe AN case, who has refeeding problems after a three
      months' hospitalisation period. She was admitted to the child intensive care unit
      due to deterioration of her vital signs. We tried to solve her problems as a
      team, and believe that AN has a number of crucial problems thus requiring a multi
      faceted treatment approach.

PMID- 15148858
TI  - Transition to adult care for adolescents with sickle cell disease: results of a
      national survey.
AB  - The objective was to present the 'voice' of adolescents with sickle cell disease
      (SCD) as part of the discussion of transition issues by identifying and
      documenting their expressed concerns and expectations, as well as what program
      priorities they perceive would facilitate a smooth transition to adult care.
      Cross-sectional data were collected by means of structured questionnaire
      interviews, using standard instruments. A volunteer sample of 172 adolescents
      with SCD aged 14 years and older still in pediatric care within community-based
      and medical center SCD programs across the United States was recruited.
      Statistically significant results indicated the top concerns of adolescents were:
      lack of information relating to their transition to adult care; fear of leaving
      the healthcare provider with whom they were already familiar, fear that adult
      care providers might not understand their needs; belief that an SCD transition
      program was needed and that it should focus on provider support; information
      provision about adult care programs; ways to meet adult care providers; and ways
      to help healthcare providers understand their needs. We conclude that many
      adolescents with SCD have concerns and fears about their transition to adult
      care. Based on findings from this study, it is recommended that transition
      programs address structural and interpersonal issues of adolescents and providers
      if they are to be successful. Strategies by which this can be achieved are
      recommended, including the need to encourage, support and provide assistance for
      peer education, outreach programs and peer-led instructions, since these hold
      great promise as approaches that are adolescent-centered and adolescent
      delivered.

PMID- 15148860
TI  - Reflections on youth and when living hurts.
AB  - Youth today usually grow up to be mature adults, but some are showing at risk
      behavior that educators and parents should be aware of and try to help and
      prevent life long social disability. The author brings some reflections to these
      issues from his life long work with children, youth, parents and educators. He
      concludes his message with teachings from the Talmud, where it is stated that if
      you can save one life, it is as though you have saved a whole world. That has now
      become his mission--one person at a time.

PMID- 15148861
TI  - Trends in autism.
AB  - Leo Kanner described autism in 1943, and Hans Asperger described the syndrome in
      1944. The term Pervasive Developmental Disorders (PDD) was first used in the
      1980s to describe a class of disorders that include (1) Autistic disorder, (2)
      Rett disorder or syndrome, (3) Childhood Disintegrative Disorder, (4) Asperger's
      disorder or syndrome, and (5) Pervasive Developmental Disorder Not Otherwise
      Specified, or PDDNOS. Autism prevalence studies published before 1985 showed
      prevalence rates of 4 to 5 per 10,000 children for the broader autism spectrum,
      and about 2 per 10,000 for the classic autism definition. Since 1985 there have
      been higher rates of autism reported from several countries. From the UK a
      prevalence rate of 16.8 per 10,000 children for autistic disorder was reported,
      and 62.6 per 10,000 for the entire autistic spectrum disorders. Sweden reported a
      prevalence of 36 per 10,000 for Asperger and 35 per 10,000 for social impairment,
      or a total prevalence of 71 per 10,000 for suspected and possible cases. From the
      US, 40 per 10,000 in three to ten year old children for autistic disorder and 67
      per 10,000 children for the entire autism spectrum was reported. From the north
      region in Israel for children born between 1989-93 in the Haifa area, an
      incidence rate of 10 per 10,000 was found for autism. In recent years concern has
      been shown about the possible increase in the prevalence of autistic spectrum
      disorders. Studies have shown an increase, but during these last twenty years
      diagnostic criteria and definition have also changed. Although many factors are
      at play, it is evident that there has been an increase.

PMID- 15148863
TI  - [How difficult it is to change scientific knowledge in policy action].

PMID- 15148862
TI  - Blindness in adolescents in Israel.
AB  - Adolescents with blindness or visual impairment, in order to go through the
      trying time of adolescence, require extra strength to overcome their disability.
      This short communication looks at prevalence data for blindness in children and
      adolescents that range from about 3 per 10,000 children in developed countries
      (60 blind children per million total population) to 15 per 10,000 in the poorest
      countries (600 blind children per million total population). Data from the year
      2000 in Israel showed a total of 18,509 persons with blindness registered in
      Israel, including 168 children between the age 0-5 years and 788 between 6-18
      years. Children and adolescents comprised 5.2% of the total with a small male
      dominance (520 males, 436 females). The total prevalence rate for children and
      adolescents (0-18 years) in Israel was 4.5 per 10,000 and 5.3 per 10,000 for the
      6-18 year olds. The causes of blindness for children and adolescents in Israel
      are also presented, with optic atrophy the most common cause.

PMID- 15148864
TI  - [Conflict of interest: results of research carried out by the Coordination for
      the integrity of biomedical research].

PMID- 15148865
TI  - [Comments on independent clinical-epidemiologic research].

PMID- 15148866
TI  - [The national Plan for the eradication of measles and congenital rubella].

PMID- 15148868
TI  - [Infant mortality and sudden crib death in Lombardy].
AB  - OBJECTIVE: To estimate the infant mortality rate and the incidence of Sudden
      Infant Death Syndrome (SIDS) which is not known in Italy. DESIGN: Retrospective
      mortality study using all deaths of resident infants occurring up to one year of
      age as recorded by the Italian Institute of Statistics, between 1994 and 1996.
      SETTING: Lombardy, Northern Italy. MAIN OUTCOME MEASURES: Infant mortality rate
      (deaths occurring in the 1st year of life), early neonatal mortality rate (1st
      7th days of life), late neonatal mortality rate (8th day of life-1st month of
      life), post-neonatal rate (1st month-one year of life), and incidence of SIDS
      (Sudden Infant Death Syndrome). RESULTS: The infant mortality rate was 4.76 per
      1,000 live births, with no significant differences among the three years and
      lower than the Italian rates. The SIDS incidence rate was 0.14 per 1,000 live
      births, and 0.39 per 1,000 live births when deaths not directly labelled as SIDS
      were considered. SIDS was the single leading cause of death in the first year of
      life after the early-neonatal period. CONCLUSIONS: The decrease of the infant
      mortality rate is due to the drop in mortality for congenital malformations and
      perinatal diseases. The incidence of SIDS in Northern Italy turns out to be low,
      while SIDS remains the single leading cause of death in the first year of life
      after the early neonatal period.

PMID- 15148867
TI  - [Several considerations on the relationship between the precautionary principle
      and evidence based prevention].

PMID- 15148869
TI  - [Description of home accidents in Piedmont based on current information sources].
AB  - OBJECTIVE: To analyse data from existing sources to assess the distribution over
      space and time of home accidents in Piedmont. DESIGN: Analysis of distribution of
      causes of hospitalisation and deaths following a home accident. SETTING: For non
      fatal accidents, we reviewed the database of hospital discharge records (HDR),
      which includes data from all hospitals in the region. For fatal accidents, we
      reviewed the data on deaths provided by the Italian National Institute of
      Statistics (ISTAT). PARTICIPANTS: All patients hospitalised for "home accidents"
      for the period 1999-2001 and deaths due to "external causes of injury and
      poisoning" and from these excluded transport accidents, homicides, and suicides
      for the period 1982-1999. RESULTS: The most commonly reported reasons for
      hospitalisation following a home accident were: fracture for 15-64 year-old age
      group and for persons aged 65 years or more (60.7% and 86% respectively) and
      intracranial transmatism for 0-14 year-old age group (33%). Regarding fatal
      accidents, the mortality rate per 100,000 was 3.6 among 0-14 year-olds, and 145.1
      among the persons aged 65 years or more. The most common cause of death was
      chocking for 0-14 year-old age-group and falls for the person aged 65 years or
      more (32.2% and 86.3% respectively). There is an excess of mortality in the
      geographical areas of Western Alps of Piemonte. CONCLUSION: In Piedmont, existing
      sources can be used to estimate the distribution of the most serious home
      accidents i.e., those resulting in hospitalisation or death. The sources we
      reviewed in this study are, at the moment, the only ones available to quantify
      and describe the phenomenon over space and time.

PMID- 15148870
TI  - [Non-conventional medicine in Tuscany: attitudes and use in the population].
AB  - OBJECTIVES: With the aim of facilitating complementary/alternative medicine (CAM)
      regulation by decision-makers in the Tuscan region, objectives of the analysis
      were: 1) to estimate the frequency and motivations of CAM use (acupuncture,
      homeopathy, phytotherapy, manipulative therapies) within the Tuscan population;
      2) to identify variables associated with CAM use; 3) to investigate public
      opinion concerning CAM. DESIGN: We have analysed the regional data collected by
      the ISTAT through the survey Multiscopo su "Condizioni di salute e ricorso ai
      servizi sanitari", years 1999-2000. PARTICIPANTS: The analysis was carried out on
      5670 subjects > 20 years resident in the Tuscan region between July 1999 and June
      2000. MAIN OUTCOME MEASURES: Usefulness, utilization and benefits concerning CAM.
      RESULTS: Forty-five percent of the surveyed population consider useful at least
      one type of CAM, and 20% had used CAM at least once in the three years prior to
      the interview. Most frequent users are middle-aged women with higher educational
      levels, and manipulative therapies and homeopathy are the most used remedies.
      Disorders that mostly have induced the population to use CAM are pain syndromes.
      CONCLUSIONS: Overall, the Tuscan population has a positive attitude towards CAM
      use, which is slightly more frequent than the average national use.

PMID- 15148871
TI  - [Hospital mortality at a cardiosurgical unit in Torino: international comparisons
      and time trend].
AB  - OBJECTIVE: To compare hospital mortality in a cardiac surgery unit with external
      data and to assess changes in time (patients undergoing surgery in two different
      periods). MATERIALS AND METHODS: Data on risk factors for hospital mortality were
      collected from clinical records (retrospectively for the first period and
      prospectively for the second) for all patients undergoing open heart surgery at
      the Heart Surgery Unit of the University of Turin (Italy) during 1991 and 1995 (n
      = 1794) and 1999 (n = 892). Comparisons of in-hospital mortality, expressed as
      Standardized Mortality Ratios (SMR), were adjusted for risk factors defined
      according to EuroSCORE (European System for Cardiac Operative Risk Evaluation).
      RESULTS: In the first and second period, complete information on all the 17
      EuroSCORE items was available for 58.3% and 89.6% patients respectively. After
      exclusion of patients with one or more missing data, observed and expected
      numbers of death were found to be very similar, with SMRs ranging between 0.82
      (isolated bypass in the second period) and 1.06 ("other" surgery in the first
      period). Mortality was higher among patients with missing data, but at least in
      1999 the latter had a limited impact on the overall estimates. Compared to the
      first period, mortality was reduced during 1999 (from 5.9% to 5.4%), in
      particular for isolated bypass (from 4.4% to 3.4%). CONCLUSIONS: In the unit
      under investigation, hospital mortality following heart surgery was similar to
      that predicted from EuroSCORE and seemed to be lower in 1999 than in 1991-95,
      particularly for isolated bypass. Incompleteness of data on individual risk
      factors may have been a source of bias, especially when data were collected
      retrospectively.

PMID- 15148872
TI  - [The precautionary principle: scientific evidence and decision processes].
AB  - We analyse conceptual and procedural approaches to the precautionary principle.
      Moreover, we describe the implications of its use in evaluation of scientific
      evidence and in decision making. In many cases evaluation of possible risks is
      influenced by individuals or groups with personal interests different from those
      of public health. Their actions discredit positive studies, giving rise to forced
      controversies and discouraging new studies. The result is to hinder checking of
      causal patterns. We report examples of historical cases and of issues rising from
      electromagnetic fields. The use of the precautionary principle is desirable both
      in issues related to global change and in possible risks associated with specific
      biological, chemical and physical agents. The precautionary principle should be
      included between values of public health evaluations and its use requires
      institutional subjects to take high responsibility for it. Both time and quality
      of analysis of causal patterns are linked to the sincere desire to solve doubts
      and defend public health interests for those who are active in public health.

PMID- 15148873
TI  - [Multiculturalism and cardiovascular diseases].
AB  - Immigration has increased drastically to the point of becoming an ordinary
      structure of our society. Once in Italy, the immigrant's health is compromised
      rapidly due to a series of conditions and illnesses that exist in our country:
      lack of work, inadequate salary, inappropriate residence, lacking family support,
      climate changes, nutritional differences. Cardiovascular illnesses represent 7.6%
      of the diseases of the immigrants, and cause 36.6% of deaths. The risk factors
      that affect the genesis of cardiovascular diseases include: subjective factors
      (age, ethnic group), environmental, nutritional and pathological (arterial
      hypertension, AIDS, tuberculosis, alcohol). The challenge for our time is to
      design a new solidarity model to promote cultural and social integration in order
      to meet the multiethnical and multiracial needs of western society. This model
      should permit reconsideration of doctor-patient relationship in order to build a
      real intercultural society.

PMID- 15148874
TI  - [Environmental impact of waste incineration].

PMID- 15148875
TI  - [Evidence based prevention and the citizens].

PMID- 15148876
TI  - In favour or against euthanasia--dentistry students' opinion.
AB  - Euthanasia and a doctor-assisted suicide are not only practiced worldwide, but
      also legalized in some countries. In Poland they are broadly discussed. The
      purpose of this paper was to define dentistry students attitude towards human
      right to ask for death and euthanasia. In the research 148 students of both sexes
      were questioned. Generally students were against euthanasia in the world as well
      as in Poland, although men were in majority for euthanasia. Believers were
      against it due to ethically-religious reasons, while non-believers were for
      euthanasia motivating it by rational reasons.

PMID- 15148878
TI  - Composite of low contraction and rapid polymerization. A study of marginal
      infiltration.
AB  - The aim of this work consists in a comparative biomorphological analysis of the
      properties of infiltration and of adhesion to dental tissues of two different
      composits (Tetric Ceram and Inten-S) with different modalities of of application
      of halogen light. The results have given evidence that there was found to be no
      significant difference between the two groups examined.

PMID- 15148877
TI  - Raman investigation of calcium carbonate bone substitutes and related
      biomaterials.
AB  - The interaction between biomaterials used in surgical procedures and the host
      bone is not yet perfectly understood. It appears that these problems may have
      been encountered because of insufficient characterisation of the basic component
      used in the synthesis of such biomaterials. Calcium carbonate (CaCO3) is
      interesting for bone filling or regeneration procedures because of its
      resorbability. The aim of this work is to compare different CaCO3 biomaterials
      and their basic source with the help of microRaman spectroscopy. Bionacre and
      Biocoral are analysed. The main bands of carbonate internal modes are observed
      around 1084-86 and 704-12 cm-1. In the lattice modes region, for both Biocoral
      and synthetic aragonite, two bands at 206 and 155 cm-1 are observed. The
      eggshell, oyster shell and synthetic calcite samples exhibit bands at 281 and 155
      cm-1. Three bands are present at 280, 206 and 155 cm-1 on the Bionacre sample.
      The 206 and the 280 cm-1 bands are due to aragonite and calcite forms
      respectively. Therefore it appears to be a mixture of aragonite and calcite
      whereas Biocoral is pure aragonite. Additional Raman investigations should be of
      great interest in evaluating the structural modifications and their influence on
      the biological behaviour of these biomaterials. Lity index, the percentage of
      prematurity and of low birth weight are the indices of national health status.

PMID- 15148879
TI  - The role of fibroblast growth factor (FGF) and type beta transforming growth
      factor (TGF-beta 1-beta 2-beta 3) during rat craniofacial development.
AB  - Growth factors seem to be part of a complex cellular signalling language, in
      which individual growth factors are the equivalents of the letters that compose
      words. According to this analogy, informational content lies, not in an
      individual growth factor, but in the entire set of growth factors and others
      signals to which a cell is exposed. The ways in which growth factors exert their
      combinatorial effects are becoming clearer as the molecular mechanisms of growth
      factors actions are being investigated. A number of related extracellular
      signalling molecules that play widespread roles in regulating development in both
      invertebrates and vertebrates constitute the Fibroblast Growth Factor (FGF) and
      type beta Transforming Growth Factor (TGF beta). The latest research literature
      about the role and fate of these Growth factors and their influence in the
      craniofacial bone growth ad development is reviewed.

PMID- 15148880
TI  - Arsenic still survives 21st century endodontics.

PMID- 15148881
TI  - [Perfusion systems for hemodialysis].
AB  - On the basis of generalizing the principles of construction and of technical
      implementation of the extracorporeal blood-transport devices applied in
      artificial purification, which were described in the 1st part of the paper,
      mathematical models are suggested to calculate the stroke volume and the
      consumption of 2-roller perfusion pumps now used in hemodialysis. The above
      models were made use of to study the influence of the constructive and
      operational characteristics per consumption originated by the mentioned pumps.

PMID- 15148882
TI  - [Basic principles of system software maintenance for multi-functional non
      invasive spectrophotometric diagnostic devices and complexes].
AB  - Due to the promotion of methods and devices of non-invasive spectrophotometric
      diagnostics in the sphere of medicine, software support for such diagnostic
      systems has been growing to be a topical issue. The general ideology of designing
      the system software support for multi-function spectrophotometric diagnostic
      tools is under discussion in the paper. The need in a multi-stratum structure of
      presenting, analyzing and processing the diagnostic findings, i.e. beginning from
      physical result interpretation to its common medical interpretation, is
      substantiated.

PMID- 15148883
TI  - [An analytical evaluation of the peripheral blood charging parameters on the
      condition of the organism and its systems].
AB  - Potentialities of analyzing the health condition of human organism and of its
      separate systems, i.e. digestive, respiratory, cardiovascular, etc., by the
      peripheral-blood parameters and with the help of the suggested AKS-ENOFIT
      analytical system are demonstrated in the paper.

PMID- 15148884
TI  - [Drug dosing device].
AB  - A device for the dosed introduction of powdery drugs into the human organism
      through the respiratory system is described. A new technical solution of drug
      introduction to prevent and treat the bronchopulmonary-ways diseases is
      suggested.

PMID- 15148885
TI  - [The phase electrocardiogram structure as viewed from the position of a refined
      model of the pulse hemodynamics].
AB  - The EKG phase structure during the cardiac cycle is presented, in which a scheme
      of separating the trans-membrance action potential into the sodium, calcium and
      potassium constituents is used and which is based on a previously developed
      qualitatively novel model related with the functional regularity of the cardio
      vascular system during the cardiac cycle. Not only the active systolic
      functioning of the myocardium but also the active (energy-dependent) diastolic
      activity is duly considered in it.

PMID- 15148886
TI  - [The use of zirconium for implants in traumatology and orthopedics].
AB  - The use of new promising materials for implanting elements in traumatology and
      orthopedics is under discussion in the paper. Steel pins coated with zirconium do
      not cause any inflammatory complications when applied. The initial results of
      using the zirconium-coated implants offer the challenge for using such devices in
      future.

PMID- 15148888
TI  - [A systemic dynamic modeling for prognosis of the quantity of the cancer patients
      in various clinical categories and for the assessment of the needs in resources].
AB  - The prognostication of a number of oncology patients and an evaluation of the
      resources' needs for the oncology service are in the focus of attention. A
      systemic dynamic model, based on a differential equations' system, is suggested
      to cope with the changing status of oncology patients. There is an example of
      using the model to forecast the number of patients with breast cancer for further
      calculation of resources needed by the palliative care service to render
      assistance to such patients and to evaluate the influence of preventive measures
      produced on the needs in resources by the mentioned service.

PMID- 15148889
TI  - [A review of the medical equipment displayed at the "Health care-2003"
      exhibition].
AB  - Medical equipment displayed at the "Healthcare-2003" exhibition, that was most
      representative in the recent years, is surveyed in the paper including the most
      novel medical devices and apparatuses as well as X-Ray, radiological, intensive
      care and neonatal equipment. Besides, outfit for diagnostics, ophthalmology and
      dentistry, laboratory medical equipment, medical instruments, technological
      medical equipment and portable medical devices were demonstrated at the
      exhibition. Therefore, considering the diversity of medical equipment displayed,
      any medical facility in Russia would be able to choose the devices it needs.

PMID- 15148887
TI  - [The technology of high-frequency cold-hot plasma ablation for small invasive
      electrosurgery].
AB  - The mechanism of high-frequency cold-plasma ablation is radically different from
      thermal impact by high-frequency current in traditional high-frequency surgery.
      As for the former, the effect is insured due to a local low-temperature molecular
      disintegration of tissue with the tissue being simultaneously removed from the
      surgery zone. The technology is based on induction of a stable plasma stratum in
      the plasma-forming medium by using a high-frequency generator. Kinetic processes
      occurring in a stationary strongly ionized plasma are under discussion in the
      paper. The function of the distribution of carriers of the ion containing (Na+,
      Cl-, K+, Cl-) plasma charge is shown to be close to Maxwellian distribution. The
      described evaluations of parameters are fundamental criteria for designing a unit
      that ensures the process of high-frequency cold-plasma ablation. Finally, the
      stability criteria were analyzed for the low-temperature plasma field.

PMID- 15148890
TI  - [A controller for medical equipment].
AB  - The structure and parameters of a universal module designed for the control
      systems of medical devices are presented in the paper. An example of applying the
      module with an actual medical device, i.e. the humidifier of medical gases, is
      described.

PMID- 15148891
TI  - [AN experience of using a digital mammograph].
AB  - The initial experience of applying a digital mammograph in Russia and the
      specific construction of its basic elements are described. Besides, the planning
      solution is presented and the clinical data are discussed.

PMID- 15148892
TI  - [Respiratory trainer TDI-22].
AB  - A small-size, transportable respiratory trainer designed for the treatment of
      bronchopulmonary diseases and made up of the air-mouthpiece, pellet and lateral
      regulating openings is described in the paper. The possibility of separate
      resistance regulation at inhale and expiration is its specificity.

PMID- 15148893
TI  - [Research-and-production enterprise "Neuron": equipment for ophthalmology].
AB  - The paper is dedicated to a small enterprise functioning in the field of medical
      engineering, i.e. the "Neuron" research-and-production Co. (Ufa), which has been
      designing and assembling the therapeutic outfit for ophthalmology.

PMID- 15148894
TI  - Tradition.

PMID- 15148895
TI  - Retinoid chemoprevention in high-risk skin cancer patients.
AB  - More commonly known for their dramatic effects on acne and psoriasis for the past
      20 years, systemic retinoids can be a valuable chemopreventive treatment option
      for those individuals in a wide variety of high-risk populations who are actively
      developing large numbers of sun-induced skin cancers.

PMID- 15148896
TI  - Pityriasis rosea: roles of the dermatology nurse.
AB  - Pityriasis rosea, a self-limited exanthematous disease of unknown etiology, is a
      fairly common exanthem encountered by dermatology nurses and nurse practitioners.
      Their special roles in diagnosis, symptomatic relief, care for patients with
      atypical rash, patient education, and counseling are described.

PMID- 15148897
TI  - Mega issues: focusing on the future of dermatology nursing.
AB  - The DNA Board of Directors met to consider the particular challenges confronting
      the dermatology nurse and the patient care team today. The following mega issues
      are the result of our combined efforts to identify those factors having the
      greatest impact on how we practice today and tomorrow: bio-nuclear terrorism;
      health care provider shortage; the provision of quality patient; education
      literature authored by nurses; emerging role and specialized educational needs of
      nurses in dermatology; and evolving therapeutic modalities.

PMID- 15148898
TI  - College students' knowledge and attitudes about cancer and perceived risks of
      developing skin cancer.
AB  - Skin cancer is the most commonly occurring cancer in the United States. Primary
      prevention practices for skin cancer are fully documented in the literature for
      reducing the damaging effects of ultraviolet radiation on skin. Late adolescents,
      inherent to their young age and risk-taking behaviors, are more likely to
      sunbathe. The cancer attitudes and suntanning knowledge, attitudes, perceptions,
      beliefs, and behaviors among college students were examined. Gender-specific
      interventions for educating this age group are recommended.

PMID- 15148899
TI  - What's your assessment? Capillary hemangioma.

PMID- 15148900
TI  - The wound healing process symphony: Part II.

PMID- 15148901
TI  - Livedo reticularis.

PMID- 15148902
TI  - Erythema ab ignis.

PMID- 15148914
TI  - Antigens Act I: scene II.

PMID- 15148915
TI  - [Application of vasoseminal vesiculography to the diagnosis of seminal ductal
      system disorders].
AB  - Vasoseminal vesiculography is becoming more and more valuable to the diagnosis of
      seminal ductal system diseases. Vasography can be performed by either trans
      scrotal injection into the vas deferens, or transperineal injection into seminal
      vesicle, or retrograde insertion of a catheter into the opening of the
      ejaculatory duct. A good knowledge of the indications and proper judgement of the
      X-ray signs may significantly improve the diagnosis and treatment of the diseases
      of the seminal vesicle and ductal system.

PMID- 15148917
TI  - [Effects of di-butyl phthalate on sperm motility and oxidative stress in rats].
AB  - OBJECTIVE: To evaluate the effects of di-butyl phthalate(DBP) on the sperm
      motility and oxidative stress in rats. METHODS: Healthy 6-week-old male Sprague
      Dawlay rats were randomly divided into 4 groups with 8 in each group. DBP
      dissolved in peanut oil was administered by gavage at dosage of 0, 250, 500,
      1,000 mg/(kg.d). After 4-week DBP exposure, the animals were killed and the
      organs were selected and weighed. The sperm VCL, VSL, VAP, BCF, ALH, LIN, MAD and
      STR in the cauda epididymis were assessed by computer assisted sperm analysis
      (CASA), and the activities of superoxide dismutase (SOD) and the contents of
      malondialdehyde (MDA) in serum and testis homogenate were measured
      simultaneously. The increase of body weight per day and the organ body weight
      ratio changes of the liver, testes and epididymides were also observed. RESULTS:
      The liver organ body weight ratios of the treated groups were higher than those
      of the control (P < 0.01), while the testis organ body weight ratios were lower
      at dosage of 1,000 mg/(kg.d) DBP. Compared with the control group, the parameters
      of rat sperm VCL and ALH declined significantly at dosage of 1,000 mg/(kg.d) DBP.
      In addition, DBP showed inhibiting effect on SOD activities in the testis, and it
      was significant in the highest exposure group compared with the control (P <
      0.05). However, there were no differences in serum SOD activities between the
      treated groups and the control. CONCLUSION: DBP exposure may affect the sperm
      motility and the anti-oxidative systems. The testis is a vital target organ
      influenced by DBP.

PMID- 15148916
TI  - [Genetic analysis of gonadotropin-gonadal axis in boys: a twin study].
AB  - OBJECTIVE: To analyse the heritabilities of serum luteinizing hormone(LH),
      follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) in twin
      boys, and to study the genetic contributions to gonadotropin-gonadal axis.
      METHODS: A total of 51 pairs of male twins, 35 monozygotic (MZ) and 16
      dizygotic(DZ) aged 5 to 11 years, were investigated. Serum gonadotropin and sex
      hormone were measured by radioimmunoassay. The twin zygosity was verified by
      determination of short tandem repeat amplified fragment length polymorphism
      systems. The genetic analysis was performed using intraclass correlation
      coefficient method. RESULTS: The intraclass correlation coefficient was greater
      in the MZ twins than in the DZ twins. The estimated heritabilities were
      respectively LH 0.51, FSH 0.32, T 0.81, E2 0.41. CONCLUSION: Genetic factors are
      major determinants of gonadotropin-gonadal axis in boys.

PMID- 15148919
TI  - [Study of varicocele and oxidative stress].
AB  - OBJECTIVE: To explore the mischief mechanism of oxidative stress in the
      varicocele (VC). METHODS: Serum was taken from the spermatic and peripheral veins
      on ligation of the internal spermatic veins in 28 infertile males with VC.
      Experimental VC was established in male rats by partial ligation of the left
      renal vein. And testis tissue was taken three months after operation. The nitric
      oxide(NO), nitric oxide synthetase (NOS), xanthine oxidase (XO), lactic acid(Lac)
      and lactic dehydrogenase (LDH) in the serum of 28 infertile males with VC and the
      testis tissue of the VC rats were detected by spectrophotometry. RESULTS: NO,
      NOS, XO and Lac in the serum of internal spermatic veins in the infertile males
      with VC were significantly higher than in the serum of peripheral veins in the VC
      patients (P < 0.01, P < 0.05). LDH was lower than that in peripheral serum. NO
      and XO of the left testis tissue in the VC rats were higher compared with the
      control group (P < 0.01). Lac in the left testis of the VC rats was lower than
      that in the control group rats (P < 0.01). CONCLUSION: NO, NOS and XO in the
      serum of the VC patients and in the testis tissues of the VC rats were increased,
      and Lac and LDH were changed obviously, which might not only disturb
      spermatogenesis, but also inhibit sperm motility. Therefore they might be one of
      the causes of infertility in VC patients.

PMID- 15148918
TI  - [Influence of epidermal growth factor and gonadotrophin on the in vitro
      maturation of human oocytes].
AB  - OBJECTIVE: To study the effect of epidermal growth factor(EGF) and different
      concentrations of gonadotrophin (Gn) on the in vitro maturation of human oocytes.
      METHODS: EGF was added to the vitro culture medium in order to observe the effect
      of Gn combined with or without EGF on the result of in vitro maturation. The
      concentrations of hCG and FSH were changed respectively to observe the difference
      between the results. RESULTS: Adding EGF to the culture medium improved the
      maturation rate of oocyte significantly (P < 0.05). There was no difference
      between the results with different concentrations of hCG and FSH in the culture
      medium. CONCLUSION: EGF can improve the results of the in vitro maturation of
      human oocytes by increasing the maturation rate significantly. Increasing the
      concentration of Gn does not influence the results of in vitro maturation.

PMID- 15148920
TI  - [Effect of Percoll selection technique on normal morphology rate and acrosin
      activity of human spermatozoa].
AB  - OBJECTIVE: To study the effect of Percoll selection technique on normal
      morphology and acrosin activity of human spermatoza. METHODS: The sperm
      morphology and sperm acrosin activity were analyzed by automated sperm morphology
      analyzer(ASMA) and spectrocolorimetry. RESULTS: The normal morphology sperm rate
      and acrosin activity were significantly increased after Percoll selection
      technique (P < 0.001). CONCLUSION: Percoll selection technique could affect
      normal morphology sperm ratio and acrosin activity.

PMID- 15148921
TI  - [Expression and significance of activated leukocyte cell adhesion molecule in
      prostatic intraepithelial neoplasia and adenocarcinoma].
AB  - OBJECTIVE: To investigate the expression of activated leukocyte cell adhesion
      molecule(ALCAM) protein in prostatic intraepithelial neoplasia and
      adenocarcinoma, and the relationship between ALCAM expression and
      clinicopathological features of prostatic carcinoma. METHODS: ALCAM protein
      expression was evaluated in the tissues of 41 human prostatic carcinomas by using
      immunohistochemistry (EnVision method). RESULTS: ALCAM was widely expressed in
      prostatic epithelia. Overexpression of ALCAM was found in most prostatic
      intraepithelial neoplasias and low-grade cancers, whereas a decreased expression
      shown in some high-grade cancers. The ALCAM protein expression in prostatic
      carcinoma was correlated with pathological grading. However, no correlation of
      ALCAM expression was found with preoperative serum prostate-specific antigen
      levels or clinical stages. CONCLUSION: Expression of ALCAM is disturbed in
      prostatic intraepithelial neoplasia and adenocarcinoma, indicating its
      involvement in the development of human prostatic carcinoma.

PMID- 15148922
TI  - [Fusion expression of Neisseria gonorrhoeae outmembrane protein with a mucosal
      adjuvant].
AB  - OBJECTIVE: To express a fusion protein of Neisseria gonorrhoeae with a mucosal
      adjuvant. METHODS: The gene coding Loop VI-VIII(PL678) of porin, an out-membrane
      protein of Neisseria gonorrhoeae, was obtained by PCR. It was inserted into a
      plasmid fused with subunit B of heat labile enterotoxin. The recombinant was
      transformed in E. coli. The expression of fusion protein was analysed by ELISA,
      SDS-PAGE and Western-blot. RESULT: Fusion protein with LTB was successfully
      expressed, and displayed both the ability of binding GM1 and the reactogenicity
      with polyclonal antibodies against Neisseria gonorrhoeae. CONCLUSION: The
      expression of fusion protein laid a foundation for the study of the
      intramolecular vaccine against Neisseria gonorrhoeae.

PMID- 15148923
TI  - [Influence of the metabolite produced by Trichomonas vaginalis on human sperm
      motility in vitro].
AB  - OBJECTIVE: To investigate the effects of the metabolite produced by Trichomonas
      vaginalis on human sperm motility in vitro. METHODS: Trichomonas vaginalis having
      been cultured, the culture solution containing metabolite was obtained by
      removing the protozoa, then diluted into 3 kinds of concentration. Sperm was
      obtained from 10 healthy fertile men by masturbation and prepared by swim-up
      technique to produce a spermatozoon solution of high motility. Every sperm sample
      was divided into 4 groups (A, B, C, D). Unused culture solution was added to
      Group A as control, and the other 3 groups (B, C, D) were respectively incubated
      with the above used culture solution at 3 kinds of concentration (1.2 x 10(9)/L,
      6 x 10(8)/L, 1.2 x 10(8)/L). Measurements were carried out at 30 s, 1 h, 2 h, 4
      h, 6 h by CASA. RESULTS: Sperm motility decreased in both Group B and C markedly,
      and the effects displayed a concentration- and time-dependent manner. CONCLUSION:
      The metabolite of Trichomonas vaginalis can reduce human sperm motility in vitro,
      and may be one of the causes of infertility.

PMID- 15148924
TI  - [Related pathogen examinations and therapeutic choices for chronic prostatitis
      following sexually transmitted diseases].
AB  - OBJECTIVE: To explore the etiologic relationship between sexually transmitted
      diseases(STDs) and chronic prostatitis (CP), and to evaluate the effect of
      multiple treatment on CP following STDs. METHODS: Seventy-two cases of CP after
      STDs were randomly divided into three groups: Group A (treated with
      levefloxatin), Group B (treated with Levofloxacin, terazosin and microwave), and
      Group C (treated with levofloxacin, Chinese traditional medicine and microwave),
      all treated for thirty days. The pathogens related to STDs in the prostatic fluid
      of all the patients had been examined before treatment. The efficacy was
      evaluated among the three groups by comparing the count of leukocytes and the
      scores of NIH-CPSI before and after treatment. RESULTS: The pathogens related to
      STDs were found in the prostatic fluid of 7 patients. The count of leukocytes and
      the scores of NIH-CPSI decreased after treatment in the three groups, more
      markedly in Groups B and C than in Group A. CONCLUSION: There is no strict
      etiological causality between STDs and CP. Multiple treatments are superior to
      single antibiotic treatment.

PMID- 15148925
TI  - [Clinical evaluation of celecoxib in treating type IIIA chronic prostatitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of celecoxib in treating
      inflammatory(Type IIIA) chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS
      IIIA type). METHODS: Sixty-four patients with diagnosed CP/CPPS-IIIA were
      randomized equally into two groups, Group A treated with celecoxib 200 mg
      daily(qd), while Group B with 200 mg twice a day(bid), both for 6 weeks. The
      white blood cell (WBC) count in expressed prostate secretion(EPS) and National
      Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) were assessed
      and compared at baseline(0 week) and at 2, 4, 6 weeks or the endpoint. RESULTS:
      The mean number of WBC in EPS and the mean NIH-CPSI total scores were decreased
      gradually after treatment from baseline in both groups. The mean number of WBC of
      in EPS of either group at the endpoint was decreased by 46.2% and 69.4%
      respectively(Group A vs Group B) compared with the baseline level. The mean NIH
      CPSI total scores of the two groups were decreased respectively by 5.6 and 8.3
      points (Group A vs Group B). In terms of the above two parameters, Group B,
      responded better than Group A to the treatment. The differences observed above
      were statistically significant(all P < 0.05). No serious adverse event presented.
      CONCLUSION: Celecoxib is effective and safe for patients with CP/CPPS(IIIA). The
      dosage of 200 mg twice a day is more efficacious than that of 200 mg daily.

PMID- 15148926
TI  - [Culture and identification of human and rabbit corpus cavernosum smooth muscle
      cells].
AB  - OBJECTIVE: To investigate an effective method to produce large numbers of pure
      corporal smooth muscle cells in vitro according to the requirement of study.
      METHODS: In this study, we used the primary tissue culture technique to isolate
      and culture the corpus cavernosum smooth muscle cells (CCSM) from human males
      with normal erectile function and New Zealand white rabbits. The cells were
      identified in regard to morphological and growing characteristics via
      immunohistochemical methods (including alpha-smooth muscle actin, desmin, myocin
      and factor VIII related antigen), special dye techniques (including Masson and
      Van Gieson) and transmission electron microscope. RESULTS: CCSM were isolated and
      cultured successfully with high purity. Morphologically, the cells were spindle
      shaped and grow on top of each other, resembling a "hill and valley" in
      appearance. When characterized in immunohistochemistry, the cells were stained
      with alpha-smooth muscle actin, desmin and myocin, but not with anti-factor VIII,
      an endothelial marker. CONCLUSION: The CCSM, which can be isolated and cultured
      successfully, may be used for further studying their biological function. The
      CCSM cultured in vitro was proved to be useful to evaluate and investigate the
      effect of some new medicine for penile erection. There is also a clinical and
      theoretical significance in further studying the experimental mechanisms of
      erectile dysfunction.

PMID- 15148928
TI  - [Determination and clinical significance of immature germ cells in human semen].
AB  - OBJECTIVE: To discuss the clinical significance of determining immature germ
      cells (IGC) in human semen. METHODS: Discontinuous Percoll gradients technique
      was employed to separate different cells and May-Grunwald-Giemsa staining and
      fluorescein isothiocyanate (FTTC)-Mab-CD45 was adopted to identify IGCs and
      leukcocytes in semen. The IGCs in 30 semen samples were determined including 10
      fertile and 20 infertile cases. RESULTS: IGCs concentrated in gradient fractions
      with 30% to 45% Percoll and leukocytes concentrated in 50%-55% Percoll fractions.
      The concentration of IGCs was (0.70 +/- 0.40) x 10(6) ml in the fertile group and
      (1.28 +/- 0.70) x 10(6)/ml in the infertile group(P < 0.05). There was no
      statistical correlation between the IGC concentration and the sperm density,
      vitality and normal morphology(P > 0.05). CONCLUSION: The use of the
      discontinuous Percoll gradient method can reach the best separation of IGCs in
      the ejaculate and it is possible to be used as a clinical index to reflect semen
      quality.

PMID- 15148927
TI  - [Multifactor analysis of bladder neck contractures after transurethral resection
      of prostate].
AB  - OBJECTIVE: To analyse different factors related to the occurrence of bladder neck
      contracture (BNC) and to find possible ways of reducing this complication.
      METHODS: All putative factors and the numbers of BNC cases were studied with
      statistical analyses in 1,017 cases that had undergone transurethral resection of
      the prostate (TURP). RESULTS: The morbidity of BNC after TURP was significantly
      higher than that of open operations. Small size of the prostate, longer time of
      operation, higher power in resection and prostatitis were factors of BNC.
      CONCLUSION: Properties of the prostate and electrical current injuries of
      resection are the primary factors of BNC. The selection of patients and
      techniques of TURP are most important in decreasing the morbidity of BNC.

PMID- 15148929
TI  - [Detection of melatonin in the serum and seminal plasma of fertile and infertile
      men].
AB  - OBJECTIVE: To detect the concentrations of melatonin(MLT) in the seminal plasma
      of fertile and infertile men. METHODS: Serum and semen were collected from 18
      fertile men aged 26-36 and 99 infertile men aged 23-36, and the latter were
      divided into five groups: normozoospermia (13 cases), oligozoospermia (27 cases),
      asthenozoospermia (31 cases), oligoasthenozoospermia (17 cases) and
      oligoasthenoteratozoospermia (11 cases). Concentrations of MLT in the serum and
      seminal plasma of the subjects were detected by ELISA. RESULTS: Concentrations of
      MLT in the serum showed no significant difference between the fertile and
      infertile men, and concentrations of MLT in the seminal plasma were lower than in
      the serum. Concentrations of MLT in the seminal plasma of the fertile men were
      not significantly different from those of the infertile men. Concentrations of
      MLT in the seminal plasma of the oligoasthenozoospermic and
      oligoasthenoteratozoospermic men were relatively lower than the fertile men, but
      the difference was not statistically significant (P > 0.05). CONCLUSIONS: MLT of
      seminal plasma may have certain effect on sperm function, but it is necessary to
      further study and clarify its mechanism.

PMID- 15148930
TI  - [Advances in the research of sperm protein 17].
AB  - Sperm protein 17 (Sp17) is a testis-specific protein involved in acrosome
      reaction in spermatozoa. However, the Sp17 gene has been recently detected in
      normal non-testis tissues and malignant neoplasias. Therefore Sp17 may be a
      potential target for immunocontraception and a suitable target for tumor
      immunotherapy. This paper reviews the advances in the protein characterization,
      expression and distribution, and biological function of Sp17 and its clinical
      research.

PMID- 15148931
TI  - [The use of color Doppler in the diagnosis of erectile dysfunction].
AB  - The technology of color Doppler ultrasonography (CDU) was more and more popularly
      applied to the clinical diagnosis of erectile dysfunction (ED) in recent years
      since its introduction into this domain by Lue et al. CDU is preferable as a
      diagnostic means for its advantages of being convenient, non-impairing and easily
      repeatable. Nowadays, CDU is becoming a hotpoint of research. However, CDU still
      has some defects that have limited its application. This article reviews its
      mechanism, usage, research development and application combined with other
      diagnostic means, and introduces a new type of power-Doppler imaging.

PMID- 15148932
TI  - [Comparison of efficacy and safety of phosphodiesterase type 5 inhibitors in the
      treatment of erectile dysfunction].
AB  - Since the introduction of the phosphodiesterase type 5 (PDE-5) inhibitor
      sildenafil in 1998, there has been a fundamental change in the treatment of
      erectile dysfunction (ED). Sildenafil has already been used by over 20 million
      men in over 100 countries, with a death rate similar to that of general
      population. The success rate of sildenafil amounts to an average of over 80%, and
      sildenafil has become the first choice for patients with ED. The development of
      two new PDE-5 inhibitors, vardenafil and tadalafil, has added to the options for
      the treatment of ED. In this review, a comparison is made of the pharmcodynamics,
      pharmacokinetics and adverse reactions between the three PDE-5 inhibitors to
      assess their efficacy and safety.

PMID- 15148933
TI  - [Genechip technology used in basic and clinical male infertility research].
AB  - Genome sequencing data have been accumulating exponentially. The detection and
      analysis of a tremendous amount of genetic information require new rapid, highly
      efficient techniques of hybridization and sequencing. The development of high
      through genechip technology has dramatically enhanced our ability in male
      infertility research. Current applications of genechip technology in male
      infertility include the study of testis genes, the analysis of spermatozoon mRNA,
      the study on cell genital toxicity, the diagnosis and treatment of male
      infertility. This review summarizes the present situation in male infertility
      research and the potential clinical application.

PMID- 15148934
TI  - [Partial penectomy combined with penis lengthening to treat penile cancer].
AB  - We used the method of partial penectomy combined with penis lengthening to treat
      2 cases of penile cancer. The penile lengths were lengthened by 3-4 cm. This
      method could retain the penis and sexual function to the maximum degree. And a
      few patients could avoid total penectomy and micturate on their feet. This
      operation is very simple and safe, with no complication.

PMID- 15148935
TI  - [Experimental research on the regulating effects of ginseng with hairy antler on
      the sexual dysfunction rat model induced with adenine].
AB  - OBJECTIVE: To research the regulating effects of different dosages of ginseng
      with hairy antler on the sexual dysfunction model of the gonad and the structure
      of shenyangxu male rats induced with adenine, and to look for the best compatible
      proportion of ginseng to hairy antler in the model. METHODS: Healthy male SD
      rats, 2 months of age and (220 +/- 20) g in weight, were randomly assigned to 13
      groups: normal group, model group, ginseng group, hairy antler group and 9
      different proportion groups of ginseng to hairy antler. Observations were made on
      the exterior syndrome, testosterone in sera, weight index of the prostate and
      seminal vesicle, and tissue changes of the testis in the experimental rat model.
      RESULTS: Dosages of different proportions of ginseng to hairy antler had
      different improving effects on the exterior syndrome, testosterone in sera,
      weight index of the prostate and seminal vesicle, and tissue changes of the
      testis. CONCLUSION: Different proportions of ginseng to hairy antler had
      different improving effects on the sexual dysfunction model of male rats induced
      with adenine, and the best compatible proportion of ginseng to hairy antler was 5
      to 2, that is, 0.45 g ginseng to 0.18 g hairy antler or 0.90 g ginseng to 0.36 g
      hairy antler.

PMID- 15148936
TI  - The Hartford Award: an exemplary honor.

PMID- 15148937
TI  - The ethics of privacy.

PMID- 15148939
TI  - Using walkie talkies to overcome the fear of separation in children having
      surgery.
AB  - Having surgery is an unnerving event for both patients and family members. But,
      when a child requires surgery, yet another fear is added to the stress equation,
      that is, the unwelcome fear of separation experienced by both the parent and
      child. This article describes an innovative protocol designed to alleviate this
      fear of separation experienced by children having surgery.

PMID- 15148938
TI  - The nurse educator role in otolaryngic allergy.
AB  - Otolaryngic allergy is a subspecialty demanding the standards of excellence for
      otolaryngic nursing described by the American Nurses Association (1994). This
      article provides a review of basic immunology, environmental control measures,
      pharmacotherapy, and immunotherapy and explores the nurse educator role in the
      care of otolaryngic allergy patients.

PMID- 15148940
TI  - Unraveling surgical assistant modifiers.
AB  - This article aims to answer frequently asked questions regarding accurate
      reporting of assistant surgeons versus assistant at surgery modifiers.

PMID- 15148941
TI  - Adolescent violence.
AB  - The purpose of this document is to provide an overview of the rising occurrences
      of adolescent violence in the American school systems and how various theories
      can be used to assist in understanding this phenomenon. The authors have become
      increasingly interested in this topic, after direct involvement in the summer of
      2001. There were a number of students who were attending summer school as a
      result of consistent out-of-school suspensions for violent acts. The procedure to
      process through the system with these students was to suspend them, resulting in
      the student subsequently failing their present grade. The school was located in a
      community known for its high rate of violence and criminal activity. Various
      types of adolescent violence exist in our schools. Studies have reported that
      violent adolescents may come from familial environments that are full of social
      and interpersonal conflicts (Gray & Foshee, 1999). This paper discusses the
      development of a research plan to investigate the number and type of adolescent
      violent occurrences in a southern middle school setting.

PMID- 15148942
TI  - Adolescent dating violence.
AB  - This article discusses how a research study will be conducted to determine
      whether there is a difference in dating violence between adolescent college
      students and older college students.

PMID- 15148944
TI  - Violent nursing education administrators: case study.

PMID- 15148943
TI  - Exploring barriers to leaving violent intimate partner relationships.
AB  - This article discusses the barriers abused partners may have for not leaving the
      violent relationship. The authors discuss procedures they will use in testing two
      clinical screening tools: the HARASS tool and the Pitts-Williams Inquiry tool.

PMID- 15148945
TI  - Anakinra: new preparation. Weakly effective in rheumatoid arthritis.
AB  - (1) There is no consensus on the best treatment option for rheumatoid arthritis
      when a first-line agent fails (most often methotrexate). Among the recent
      immunosuppressants, etanercept should be used before infliximab. (2) Anakinra, an
      interleukin-1 type 1 receptor antagonist, was recently authorised in the European
      Union as a second-line treatment for rheumatoid arthritis in combination with
      methotrexate. (3) There are no published trials comparing anakinra with other
      slow-acting antirheumatic drugs (especially infliximab and etanercept). In one
      clinical trial in patients who did not respond adequately to methotrexate, the
      combination anakinra + methotrexate was more effective than methotrexate +
      placebo on ACR 20%, ACR 50% and ACR 70% criteria, but the clinical relevance of
      these results is doubtful. (4) An indirect comparison suggests that etanercept is
      more effective than anakinra + methotrexate. (5) In a placebo-controlled trial of
      anakinra, 75% of patients had reactions at the injection site. Serious
      infections, neutropenia and anti-anakinra antibodies were also reported. There is
      no evidence that anakinra is any safer than etanercept. (6) Anakinra + etanercept
      offers no gains in efficacy, just an increased risk of severe infections. (7)
      Subcutaneous injections of anakinra are required daily (twice-weekly subcutaneous
      injections for etanercept). (8) In short, there is no argument for using anakinra
      as a second-line treatment for rheumatoid arthritis; it does not improve disease
      management.

PMID- 15148946
TI  - The deprivation argument against abortion.
AB  - The most plausible pro-life argument claims that abortion is seriously wrong
      because it deprives the foetus of something valuable. This paper examines two
      recent versions of this argument. Don Marquis's version takes the valuable thing
      to be a 'future like ours', a future containing valuable experiences and
      activities. Jim Stone's version takes the valuable thing to be a future
      containing conscious goods, which it is the foetus's biological nature to make
      itself have. I give three grounds for rejecting these arguments. First, they lead
      to unacceptable inequalities in the wrongness of killing. Second, they lead to
      counterintuitive results in a range of imaginary cases. Third, they ignore the
      role of psychological connectedness in determining the magnitude or seriousness
      of deprivation-based harms: because the foetus is only weakly psychologically
      connected to its own future, it cannot be seriously harmed by being deprived of
      that future.

PMID- 15148947
TI  - Doctors in the decent society: torture, ill-treatment and civic duty.
AB  - How should physicians act when faced with corporal punishment, such as
      amputation, or torture? In most cases, the answer is clear: international law, UN
      resolutions and universal codes of medical ethics absolutely forbid physicians
      from countenancing torture and corporal punishment in any form. An acute problem
      arises, however, in decent societies, but not necessarily liberal states, that
      are, nonetheless, welcome in the world community. The decent society is often
      governed, in whole or in part, by religious laws, and while these states abridge
      various human rights they are peace loving, generally tolerant, and offer their
      citizens wide avenues for political participation. Under these circumstances the
      prohibition against corporal punishment and torture weakens, often compelling
      physicians to participate. This is true in two cases. In Rawls' hypothetical
      nation of Kazanistan, Islamic law is the order of the day, and amputations and
      corporal punishment play an integral part in the execution of traditional Islamic
      justice. In Israel, torture is sometimes used to elicit the information needed to
      thwart impending terror attacks. In each case, a physician's participation is
      essential. In light of the near universal condemnation that accompanies torture
      and corporal punishment, physicians can only appeal to norms anchored in
      collective well-being and concern for life that override respect for human
      dignity in these societies. Western societies have consistently rejected this
      reasoning, but it is part and parcel of life in the decent society.

PMID- 15148948
TI  - Workforce investments for the future.

PMID- 15148950
TI  - The Golden Rule and the potentiality principle: future persons and contingent
      interests.
AB  - Duties to future persons are central to numerous key ethical issues including
      contraception, abortion, genetic selection, treatment of the environment, and
      population control. Nevertheless, we still seem to be lacking Parfit's 'Theory
      X', a general theory of beneficence whose appropriateness extends to future
      generations. Starting from the Golden Rule (TGR), R.M. Hare purportedly derived
      counterintuitive duties to potential people and 'the potentiality principle'.
      However, I argue that Hare's derivation involves a hidden and unjustifiable
      extension from TGR, and show how the most plausible form of TGR is compatible
      with multiple contradictory principles for the treatment of future persons. I
      appeal to our own preferences to argue that one extension of TGR follows the
      spirit of TGR, while the other is deeply implausible. Using the plausible
      extension, I derive a Contingent Interests Principle (CIP) that offers much
      promise as Parfit's elusive Theory X. In contrast to Hare's interpretation of
      TGR, this application provides solid justification for rejecting the potentiality
      principle.

PMID- 15148949
TI  - Challenging the bioethical application of the autonomy principle within
      multicultural societies.
AB  - This article critically re-examines the application of the principle of patient
      autonomy within bioethics. In complex societies such as those found in North
      America and Europe health care professionals are increasingly confronted by
      patients from diverse ethnic, cultural, and religious backgrounds. This affects
      the relationship between clinicians and patients to the extent that patients'
      deliberations upon the proposed courses of treatment can, in various ways and to
      varying extents, be influenced by their ethnic, cultural, and religious
      commitments. The principle of patient autonomy is the main normative constraint
      imposed upon medical treatment. Bioethicists typically appeal to the principle of
      patient autonomy as a means for generally attempting to resolve conflict between
      patients and clinicians. In recent years a number of bioethicists have responded
      to the condition of multiculturalism by arguing that the autonomy principle
      provides the basis for a common moral discourse capable of regulating the
      relationship between clinicians and patients in those situations where patients'
      beliefs and commitments do or may contradict the ethos of biomedicine. This
      article challenges that claim. I argue that the precise manner in which the
      autonomy principle is philosophically formulated within such accounts prohibits
      bioethicists' deployment of autonomy as a core ideal for a common moral discourse
      within multicultural societies. The formulation of autonomy underlying such
      accounts cannot be extended to simply assimilate individuals' most fundamental
      religious and cultural commitments and affiliations per se. I challenge the
      assumption that respecting prospective patients' fundamental religious and
      cultural commitments is necessarily always compatible with respecting their
      autonomy. I argue that the character of some peoples' relationship with their
      cultural or religious community acts to significantly constrain the possibilities
      for acting autonomously. The implication is clear. The autonomy principle may be
      presently invalidly applied in certain circumstances because the conditions for
      the exercise of autonomy have not been fully or even adequately satisfied. This
      is a controversial claim. The precise terms of my argument, while addressing the
      specific application of the autonomy principle within bioethics, will resonate
      beyond this sphere and raises questions for attempts to establish a common moral
      discourse upon the ideal of personal autonomy within multicultural societies
      generally.

PMID- 15148952
TI  - Capacities, context and moral status of animals.
AB  - According to a widely shared intuition, normal adult humans require greater moral
      concern than normal, adult animals in at least some circumstances. Even the most
      steadfast defenders of animals' moral status attempt to accommodate this
      intuition, often by holding that humans' higher-level capacities (intellect,
      linguistic ability, and so on) give rise to a greater number of interests, and
      thus the likelihood of greater satisfaction, thereby making their lives more
      valuable. However, the moves from capacities to interests, and from interests to
      the likelihood of satisfaction, have up to now gone unexamined and undefended. I
      argue that context plays a morally significant role both in the formation of an
      individual's capacities, and in the determination of the individual's interests
      and potential for satisfaction based on those capacities. Claims about an
      individual's capacities and interests are typically presented as unconditional;
      but on closer examination, they are revealed to be contingent on tacit
      assumptions about context. Until we develop an understanding of how to account
      for the role of context within our moral theories, attempts to defend special
      moral concern for human beings based on their superior capacities are less firmly
      grounded than is commonly thought.

PMID- 15148951
TI  - Carl Cohen's 'kind' arguments for animal rights and against human rights.
AB  - Carl Cohen's arguments against animal rights are shown to be unsound. His
      strategy entails that animals have rights, that humans do not, the negations of
      those conclusions, and other false and inconsistent implications. His main
      premise seems to imply that one can fail all tests and assignments in a class and
      yet easily pass if one's peers are passing and that one can become a convicted
      criminal merely by setting foot in a prison. However, since his moral principles
      imply that nearly all exploitive uses of animals are wrong anyway, foes of animal
      rights are advised to seek philosophical consolations elsewhere. I note that some
      other philosophers' arguments are subject to similar objections.

PMID- 15148953
TI  - [Results of molecular target antineoplastic agents screening].

PMID- 15148955
TI  - [The 108th annual meeting of the Japanese Ophthalmological Society.  Tokyo,
      Japan. April 15-18, 2004. Abstracts].

PMID- 15148954
TI  - Olanzapine: new indication. New indication in acute mania: just another
      neuroleptic.
AB  - (1) Lithium is the first-line treatment for patients with acute mania. For
      patients with psychosis or intense agitation, an oral neuroleptic can be added
      (haloperidol or chlorpromazine, the best-assessed drugs of this class). (2) The
      licensed indications for oral olanzapine, a neuroleptic, explicitly mention the
      treatment of acute mania. (3) The clinical evaluation dossier on olanzapine in
      this setting (10 mg to 15 mg/day) is not particularly impressive. In particular,
      clinical trials included patients with a variety of associated psychotic
      symptoms. (4) The only comparative trial against another neuroleptic, haloperidol
      at a high starting dose (10 mg), showed that olanzapine was no more effective.
      The same applies to a trial comparing olanzapine with disodium valproate. (5) One
      placebo-controlled trial tested olanzapine as an additional treatment in patients
      who did not respond adequately to lithium or valproate disodium. Olanzapine
      potentiated the antimanic effects of the original treatment but also increased
      the incidence of adverse effects. (6) In patients with acute mania, the main
      adverse effects of olanzapine are drowsiness, weight gain, dizziness, and dry
      mouth. In the trial comparing olanzapine with haloperidol, olanzapine caused
      fewer extrapyramidal side effects but more weight gain than haloperidol. (7)
      Olanzapine costs 20 times more than haloperidol in France. (8) In practice,
      olanzapine is just another neuroleptic approved for the treatment of acute mania
      in patients with psychotic symptoms and agitation. There is no evidence that
      olanzapine has the best risk-benefit ratio in this category.

PMID- 15148956
TI  - Caspofungin: new indication. No progress in invasive candidiasis.
AB  - (1) The reference treatment for invasive candidiasis in patients without
      neutropenia is standard amphotericin B. If this treatment fails or is too
      nephrotoxic, second-line alternatives are liposomal amphotericin B and
      fluconazole. Voriconazole is a third-line option. (2) Caspofungin, an antifungal
      drug belonging to the echinocandin class, is now approved for use in this
      indication in France. (3) The clinical evaluation dossier contains no data from
      comparative trials with fluconazole or voriconazole. It only gives the results of
      a double-blind trial in 239 patients, designed to show simply that caspofungin
      was not inferior to standard amphotericin B. Most of the patients did not have
      neutropenia. About one-third of the patients died. There was no difference in
      mortality between the two groups. No data are available from trials versus other
      forms of amphotericin B. (4) In this trial, caspofungin had fewer adverse effects
      (especially nephrotoxicity) than standard amphotericin B. However, in other
      trials in other indications, caspofungin had more adverse effects than
      fluconazole. (5) In France, caspofungin costs nearly 100 times more than standard
      amphotericin B. (6) In practice, caspofungin has no proven advantages over
      existing options for the treatment of invasive candidiasis in patients without
      neutropenia.

PMID- 15148958
TI  - [The 88th Congress of the Japanese Society of Legal Medicine. Hokkaido, Japan.
      June 2-4, 2004. Abstracts].

PMID- 15148957
TI  - [The 47th annual meeting of the Japanese Society of Nephrology. Tochigi, Japan.
      May 27-29, 2004. Abstracts].

PMID- 15148959
TI  - The Midas touch.

PMID- 15148960
TI  - Close space to treat missing lateral incisors.

PMID- 15148961
TI  - Eggplant anaphylaxis in a patient with latex allergy.

PMID- 15148963
TI  - Late-onset anaphylaxis to Bacillus natto-fermented soybeans (natto).

PMID- 15148962
TI  - Combination of CC16, GSTM1, and GSTT1 genetic polymorphisms is associated with
      asthma.

PMID- 15148964
TI  - Peanut allergy: sensitization by peanut oil-containing local therapeutics seems
      unlikely.

PMID- 15148965
TI  - Breast-feeding, atopy, and asthma.

PMID- 15148966
TI  - Starlink genetically modified corn and allergenicity in an individual.

PMID- 15148967
TI  - The scandal that persuaded ministers to "let go" of the NHS.

PMID- 15148968
TI  - On location--sick city looks to ease burden of acute care.

PMID- 15148969
TI  - Regulation ideas. Commission control.

PMID- 15148970
TI  - Six-component vaccines: new preparations. Simpler hepatitis B vaccination of
      infants.
AB  - (1) Two six-component vaccines available in France (Hexavac and InfanrixHexa) are
      designed for primary and booster vaccination of infants. A single intramuscular
      injection delivers a five-component vaccine (diphtheria, tetanus, poliomyelitis,
      Haemophilus influenzae type b and acellular pertussis) and a hepatitis B vaccine.
      (2) The clinical evaluation dossier on InfanrixHexa includes four trials versus
      separate injections of a five-component vaccine and a hepatitis B vaccine at two
      distinct sites. (3) For primary vaccination, no difference in immunogenicity was
      found between InfanrixHexa and separate vaccination for 5 of the 6 components.
      The serological response to Haemophilus was weaker with InfanrixHexa, but whether
      or not this translates into worse long-term clinical protection is unknown. (4)
      After primary vaccination, major adverse events were a little rarer with
      InfanrixHexa than with separate vaccination. There was no difference in adverse
      events between InfanrixHexa and separate vaccination after the recommended
      booster between the ages of 16 and 18 months. (5) Evaluation data on Hexavac
      published by Aventis Pasteur MSD are very limited. We found only one trial in the
      primary vaccination setting, versus vaccination at two distinct sites with a five
      component vaccine and a hepatitis B vaccine. (6) The serological response to
      hepatitis B virus and Haemophilus was significantly weaker with Hexavac than with
      separate vaccination, but no difference was found regarding the other four
      components. It is not known if this difference has any clinical implications.
      There was no difference in adverse events between Hexavac and separate
      vaccination. (7) The vaccination schedule depends on whether or not separate
      hepatitis B vaccine is required at birth. A six-component vaccine and a five
      component vaccine can be used alternately.

PMID- 15148972
TI  - Lamivudine 300 mg in HIV infection: dose change. Once-a-day dosing.
AB  - Lamivudine is now available as 300 mg tablets for once-a-day treatment of HIV
      infected adults. In HIV-infected adults, 300 mg lamivudine in a single daily dose
      has similar efficacy to 150 mg lamivudine in two daily doses. The 300-mg tablets
      may make treatment more convenient.

PMID- 15148971
TI  - Nifuroxazide: licence modification. New restrictions in children.
AB  - It would be best simply not to use nifuroxazide, an antibacterial agent with no
      proven specific clinical action. Oral rehydration remains the cornerstone of
      treatment in this setting.

PMID- 15148973
TI  - Bupropion (amfebutamone): French pharmacovigilance data.

PMID- 15148974
TI  - Extrapyramidal reactions to SSRI antidepressant + neuroleptic combinations.

PMID- 15148975
TI  - Fluoxetine + hydromorphone: serotonin syndrome?

PMID- 15148977
TI  - Ephedrine and tiratricol: freshly prepared mixtures forbidden in France.

PMID- 15148976
TI  - Venlafaxine + tramadol: serotonin syndrome.

PMID- 15148978
TI  - Spironolactone + ace inhibitor or sartan: risk of hyperkalaemia.

PMID- 15148979
TI  - Mirtazapine: seizures and neutropenia.

PMID- 15148980
TI  - No sartans during pregnancy.

PMID- 15148981
TI  - Pilosuryl and severe diethylene glycol intoxication.

PMID- 15148983
TI  - Hexavalent vaccination and sudden death.

PMID- 15148982
TI  - Venous thrombosis with cyproterone (continued).

PMID- 15148985
TI  - Industrial interests versus public health: the gap is growing.
AB  - (1) Drug companies pretending to innovate; health authorities pretending to
      regulate; medicines agencies pretending to be transparent: the main players in
      the medicines roadshow had their hands full in 2003, with little time for
      patients and their daily concerns. (2) On a more optimistic note, 2003 also saw
      civil society contributing forcefully to the debate on the future European
      legislative framework on medicines. One result is that medicines agencies will
      have to be more transparent in future.

PMID- 15148984
TI  - Atrial fibrillation: rate control often better than rhythm control.
AB  - (1) The treatment aims in atrial fibrillation are to reduce patients' symptoms
      and to prevent both embolism and deterioration of any underlying heart disease.
      Therapy consists of anticoagulant or antiplatelet drugs, treatment of any
      underlying heart disease, and heart rate control. (2) Digoxin, betablockers,
      diltiazem and verapamil slow the heart rate but rarely restore sinus rhythm.
      Amiodarone, disopyramide, flecainide, quinidine and sotalol can be used to
      prevent relapse of atrial fibrillation after electrical cardioversion, but they
      all have potentially serious adverse effects. New trials of antiarrhythmic
      treatments have been published since our last review of this subject. (3) In one
      trial in 403 patients, amiodarone was more effective than sotalol and propafenone
      in restoring and maintaining sinus rhythm. After 15 months of follow-up, there
      were fewer strokes among patients treated with amiodarone, but there was no
      difference between the three drugs in the overall incidence of cardiovascular
      events. (4) A clinical trial with 4060 patients compared rhythm control (mainly
      with amiodarone, sotalol or propafenone; sometimes combined with electrical
      cardioversion) and rate control (with digoxin, betablocker, diltiazem or
      verapamil; systematically combined with anticoagulant therapy). The
      antiarrhythmic treatment restored sinus rhythm in more than half the patients in
      the long term. But rhythm control did not reduce the risk of death or serious
      cardiovascular events during a mean follow-up period of 3.5 years. Rhythm control
      caused more adverse events than rate control; subgroup analyses (weak evidence)
      suggest that rhythm control may also have caused more deaths among patients over
      65 and among patients with coronary heart disease. (5) In another trial,
      electrical cardioversion followed by antiarrhythmic therapy (mainly sotalol)
      sustainably restored sinus rhythm in more than one-third of 522 patients. But,
      compared with rate control treatment plus anticoagulant therapy, rhythm control
      did not reduce the risk of cardiovascular events, and was associated with a
      larger number of serious adverse cardiac effects. (6) Other recent trials confirm
      the risk of serious adverse effects, including severe arrhythmia with sotalol
      (especially at the start of treatment), and adverse thyroid and pulmonary effects
      with amiodarone. (7) Combined radiofrequency ablation and cardiac stimulation
      improved symptoms in some patients with incapacitating atrial fibrillation who
      had not responded to other treatments. However, this approach carries a risk of
      serious adverse effects, and its impact on the risk of cardiovascular events and
      death is not known. (8) In practice, an attempt should be made to restore sinus
      rhythm with amiodarone and/or electrical cardioversion, in symptomatic, recent or
      paroxysmal atrial fibrillation in patients under 65 who have no signs or symptoms
      of coronary heart disease. In other situations, rate control is the first-line
      option, using digoxin, betablockers (other than sotalol) or calcium channel
      blockers (diltiazem or verapamil). Whatever the option, treatment must be
      combined with anticoagulant or antiplatelet therapy, and with treatment of any
      underlying heart disease.

PMID- 15148986
TI  - Prion protein and the molecular features of transmissible spongiform
      encephalopathy agents.
AB  - Transmissible spongiform encephalopathy (TSE) diseases, or prion diseases, are
      neurodegenerative diseases found in a number of mammals, including man. Although
      they are generally rare, TSEs are always fatal, and as of yet there are no
      practical therapeutic avenues to slow the course of disease. The epidemic of
      bovine spongiform encephalopathy (BSE) in the UK greatly increased the awareness
      of TSE diseases. Although it appears that BSE has not spread to North America,
      chronic wasting disease (CWD), a TSE found in cervids, is causing significant
      concern. Despite decades of investigation, the exact nature of the infectious
      agent of the TSEs is still controversial. Although many questions remain,
      substantial efforts have been made to understand the molecular features of TSE
      agents, with the hope of enhancing diagnosis and treatment of disease, as well as
      understanding the fundamental nature of the infectious agent itself. This review
      summarizes the current understanding of these molecular features, focusing on the
      role of the prion protein (PrP(c)) and its relationship to the disease-associated
      isoform (PrP(Sc)).

PMID- 15148987
TI  - Past, present and future of bovine spongiform encephalopathy in France.
AB  - The bovine spongiform encephalopathy (BSE) epidemic has been monitored in France
      since the end of 1990. The surveillance has been considerably enhanced since
      2000, and today every cow aged 2 years or more is tested at the time of
      slaughter, culling or death. As of 1 May 2002, 613 native cases have been
      identified, 287 of them by the mandatory reporting system of suspect clinical
      cases or complementary programs, 213 by active surveillance of fallen stock and
      113 by testing at the abattoir. The analysis of reported BSE cases shows a higher
      number of cases born between 1993 and 1995, which can be linked to a greater
      exposure at that time and to an increase in surveillance efficiency. When the
      clinical onset related to overexposure ends, the future trend of the BSE epidemic
      in France will depend on the efficiency of the control measures implemented since
      1996. An indicator of this will be the number of BSE cases born among recent
      cohorts. Bovine spongiform encephalopathy (BSE) was described first in 1987 in
      Great Britain (Wells et al. 1987), where a huge epidemic started, and more than
      180,000 cases have been detected since then in this country. A risk analysis
      undertaken in France in 1990, in part because of the amount of meat and bone meal
      (MBM) imported from Great Britain during the 1980s, led to the conclusion that
      BSE might have spread to France, and that sporadic cases might be observed (Savey
      et al. 1991). Epidemiological surveillance was therefore set up at the end of
      1990, and control measures were taken to prevent the development of the disease.
      The trends in the number of BSE cases detected in France must be analyzed in the
      light of both the detection system and the control measures, as well as their
      changes over time.

PMID- 15148989
TI  - Public health and the BSE epidemic.
AB  - Bovine Spongiform Encephalopathy was discovered in 1986 in the United Kingdom and
      relatively rapidly spread into its trading partners in Europe via contaminated
      cattle feed supplements. The practice of using the discarded bovine carcass as
      cattle feed supplements led to the recycling of the prion agent and the
      consequent generation of new point source epidemics in the recipient countries.
      The advent of rapid diagnostic tests and more widespread testing has led to the
      identification of BSE in countries not previously reporting cases and the
      recognition of larger numbers of infections in countries previously only
      reporting clinical cases. The recognition of the wider spread of BSE and the 1996
      recognition of vCJD as a human disease caused by consumption of BSE agent led to
      international concerns regarding the threat to human health and the demand for
      stricter controls on human food derived from cattle. Major shifts in food safety
      policy have occurred as a direct result. The recommendation that risk assessments
      for BSE infectivity and human exposure pathways be conducted rather than reliance
      upon rates and simple enumeration of BSE cases is one of the most prominent
      changes in the basis of policy regarding human health. The movement of BSE into
      human populations has a wider impact than seen in food safety--surgical
      procedures, blood, cells, tissues and organ donation programs are all affected.
      The World Health Organization has recommended that 'the eradication of BSE must
      remain the principle public health objective of national and international animal
      health control authorities'. The opinions expressed in this chapter are those of
      the author and do not necessarily reflect the views of Health Canada. This review
      was written while the author was employed at the WHO.

PMID- 15148988
TI  - Pathology and pathogenesis of bovine spongiform encephalopathy and scrapie.
AB  - In common with other prion diseases or transmissible spongiform encephalopathies
      (TSEs), scrapie of sheep and bovine spongiform encephalopathy (BSE) are
      characterized by grey matter vacuolation and accumulation of an abnormal isoform
      of the host prion protein (PrP) in the central nervous system (CNS). In apparent
      contrast with human disease, neither neuronal loss nor gliosis are invariable
      features of the pathology of domestic food animal TSEs. In sheep, accumulation of
      abnormal PrP may also occur in the lymphoreticular and peripheral nervous systems
      where it may be detected within months of birth. The involvement of tissues other
      than CNS is influenced by dose, PrP genotype of the host and strain of TSE agent.
      Although many different strains of scrapie agent have been isolated in rodents
      following serial passage of affected sheep brain tissue, the significance of
      these murine strains for natural sheep scrapie, and the extent to which different
      sheep scrapie strains occur naturally are uncertain. Whereas the consistent
      vacuolar pattern in the brains of BSE-affected cattle suggests a single strain of
      agent, the patterns of vacuolation in sheep scrapie are highly variable and
      cannot be easily used to define strain. In sheep scrapie, immunohistochemistry
      can be used to visualize different morphological types of abnormal PrP within
      individual brains. These different types of PrP accumulation seem to be
      associated with different brain cell types and with variation in the processing
      of abnormal PrP. When assessed in whole brain, different patterns of PrP
      accumulation are helpful in distinguishing between different sheep scrapie
      strains and also between ovine BSE and natural sheep scrapie.

PMID- 15148991
TI  - Neuropathology and molecular biology of variant Creutzfeldt-Jakob disease.
AB  - The neuropathological features of human prion diseases are spongiform change,
      neuronal loss, astrocytic proliferation and the accumulation of PrP(Sc), the
      abnormal isoform of prion protein (PrP). The pattern of brain involvement is
      remarkably variable and is substantially influenced by the host PrP genotype and
      PrP(Sc) isotype. Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion
      disease which results from exposure to the bovine spongiform encephalopathy (BSE)
      agent. The neuropathology of vCJD shows consistent characteristics, with abundant
      florid and cluster plaques in the cerebrum and cerebellum, and widespread
      accumulation of PrP(res) on immunocytochemistry. These features are distinct from
      all other types of human prion disease. Spongiform change is most marked in the
      basal ganglia, while the thalamus exhibits severe neuronal loss and gliosis in
      the posterior nuclei. These areas of thalamic pathology correlate with the areas
      of high signal seen in the thalamus on magnetic resonance imaging (MRI)
      examination of the brain. Western blot analysis of PrP(Sc) in the brain in vCJD
      tissue shows a uniform isotype, with a glycoform ratio characterized by
      predominance of the diglycosylated band, distinct from sporadic CJD. PrP(Sc)
      accumulation in vCJD is readily detectable outside the brain, in contrast with
      other forms of human prion disease, particularly in the lymphoid system and in
      parts of the peripheral nervous system. This has raised concern about the
      possible iatrogenic transmission of vCJD by contaminated surgical instruments, or
      blood. All cases of vCJD are methionine homozygotes at codon 129 of the prion
      protein gene (PRNP). Continued surveillance is required to investigate cases of
      vCJD in the UK and other countries where BSE has been reported, particularly as
      cases of 'human BSE' in individuals who are MV or VV at codon 129 of the PrP gene
      have not yet been identified. Histological, genetic and biochemical techniques
      are essential tools for the adequate diagnosis and investigation of human prion
      diseases.

PMID- 15148990
TI  - Clinical features of variant Creutzfeldt-Jakob disease.
AB  - The possibility that a new form of human prion disease, variant Creutzfeldt-Jakob
      disease (vCJD) had occurred in the UK was first raised by the identification of a
      small number of cases with unusual clinical characteristics. Atypical features
      included a young age at death, a predominantly psychiatric presentation, a
      relatively extended duration of illness and the absence of the 'typical' periodic
      electroencephalogram seen in sporadic CJD. Diagnostic criteria for vCJD have now
      been formulated and partially validated. Magnetic resonance imaging of the brain
      shows high signal in the posterior thalamus in the great majority of cases and
      all tested cases to date have been methionine homozygous at codon 129 of the
      prion protein gene (PRNP). There is a need to try and improve early diagnosis,
      particularly if effective treatments are developed.

PMID- 15148992
TI  - The epidemiology of variant Creutzfeldt-Jakob disease.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) was identified as a new disease in 1996.
      It was linked to infection with the bovine spongiform encephalopathy (BSE) agent
      although the epidemiological evidence for this was not strong, but later strain
      typing studies confirmed the association. The disease has affected predominantly
      young adults whose dietary and other characteristics are unexceptional compared
      to control groups, other than that all patients to date have been methoinine
      homozygous at codon 129 of the prion protein gene and the incidence has been
      about two times higher in the North of the UK. The number of cases in the 7 years
      after first identification of the disease has been considerably lower than
      initially feared, given the likely widespread exposure of the UK population to
      the BSE agent through contaminated beef products. Predictions of the possible
      future course of the epidemic have many associated uncertainties, but current
      mathematical models suggest that more than a few thousand cases is unlikely. Such
      modelling is limited by the absence of a test for infection with the vCJD agent.
      The development of a test that could be used on easily accessible tissue to
      detect infection early in the incubation period would not only advance
      understanding of the epidemiology of infection with the agent but would also aid
      the implementation of control measures to prevent potential iatrogenic spread.

PMID- 15148993
TI  - Chronic wasting disease of cervids.
AB  - Chronic wasting disease (CWD) has recently emerged in North America as an
      important prion disease of captive and free-ranging cervids (species in the deer
      family). CWD is the only recognized transmissible spongiform encephalopathy (TSE)
      affecting free-ranging species. Three cervid species, mule deer (Odocoileus
      hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus
      elaphus nelsoni), are the only known natural hosts of CWD. Endemic CWD is well
      established in southern Wyoming and northern Colorado, and has been present in
      this 'core area' for two decades or more. Apparently CWD has also infected farmed
      cervids in numerous jurisdictions, and has probably been endemic in North
      America's farmed deer and elk for well over a decade. Several free-ranging foci
      distant to the Colorado-Wyoming core area have been discovered since 2000, and
      new or intensified surveillance may well identify even more foci of infection.
      Whether all of the identified captive and free-ranging foci are connected via a
      common original exposure source remains undetermined. Some of this recently
      observed 'spread' may be attributable to improved detection or natural movements
      of infected deer and elk, but more distant range extensions are more likely
      caused by movements of infected captive deer and elk in commerce, or by some yet
      unidentified exposure risk factor. Research on CWD over the last 5 years has
      resulted in a more complete understanding of its pathogenesis and epidemiology.
      CWD is infectious, transmitting horizontally from infected to susceptible
      cervids. Early accumulation of PrP(CWD) in alimentary tract-associated lymphoid
      tissues during incubation suggests agent shedding in feces or saliva as plausible
      transmission routes. Residual infectivity in contaminated environments also
      appears to be important in sustaining epidemics. Improved tests allow CWD to be
      reliably diagnosed long before clinical signs appear. Implications of CWD are not
      entirely clear at this time. Natural transmission to humans or traditional
      domestic livestock seems relatively unlikely, but the possibility still evokes
      public concerns; impacts on wildlife resources have not been determined.
      Consequently, where CWD is not known to occur surveillance programs and
      regulations that prevent or reduce the likelihood that CWD will be introduced
      into these jurisdictions should be encouraged. Where CWD is known to occur,
      affected jurisdictions are conducting surveillance to estimate and monitor trends
      in geographic distribution and prevalence, managing deer and elk populations in
      attempts to limit spread, and developing and evaluating techniques for further
      controlling and perhaps eradicating CWD. Programs for addressing the challenges
      of CWD management will require interagency cooperation, commitment of funds and
      personnel, and applied research. Chronic wasting disease (CWD) is perhaps the
      most enigmatic of the naturally occurring prion diseases. Although recognized as
      a transmissible spongiform encephalopathy (TSE) since the late 1970s (Williams
      and Young 1980, 1982), interest in and concern about CWD has only recently
      emerged. CWD most closely resembles scrapie in sheep in most respects, but recent
      media and public reaction to CWD has been more reminiscent of that afforded to
      bovine spongiform encephalopathy (BSE) less than a decade ago. Yet, with the
      exception of transmissible mink encephalopathy (TME), CWD is the rarest of the
      known animal TSEs: fewer than 1,000 cases have been diagnosed worldwide, and all
      but two of these occurred in North America. CWD is unique among the TSEs in that
      it affects free-living species (Spraker et al. 1997; Miller et al. 2000). The
      three natural host species for CWD, mule deer (Odocoileus hemionus), white-tailed
      deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni), are all
      in the family Cervidae and native to North America. Like scrapie, CWD is
      contagious: epidemics are self-sustaining in both captive and free-ranging cervid
      populations (Miller et al. 1998, 2000). The geographic extent of endemic CWD in
      free-ranging wildlife was initially thought to be quite limited and its natural
      rate of expansion slow; however, recent investigations have revealed that CWD has
      been inadvertently spread much more widely via market-driven movements of
      infected, farmed elk and deer. Both the ecological and economic consequences of
      CWD and its spread remain to be determined; moreover, public health implications
      remain a question of intense interest. Here, we review current understanding of
      CWD, its implications, and its management.

PMID- 15148994
TI  - Gastrointestinal manifestations and complications of Henoch-Schonlein purpura.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is a systemic vasculitic disorder
      commonly affecting young children. Gastrointestinal (GI) involvement is
      frequently seen, and it varies from mild symptoms to severe complications.
      METHODS: In the 5 years from July 1995 to June 2000, 208 children were diagnosed
      with HSP in our hospital. There were 116 males and 92 females with ages ranging
      from 9 months to 15 years (mean, 6.4 years; median, 5.5 years). Their medical
      records were reviewed. We focused on their gastrointestinal manifestations and
      complications. The hospital course and management of these patients were also
      analyzed. RESULTS: GI manifestations were present in 162 cases (77.8%), and among
      them the most common presentation was colicky abdominal pain in 159 cases
      (98.1%), followed by vomiting in 64 cases (39.5%). Severe complications included
      massive GI bleeding in 5 patients, intussusception in 1, protein-losing
      enteropathy in 1, and a patient with pancreatitis. GI symptoms occurred before
      the manifestation of skin lesions in 41 patients (25.3%). Five of them underwent
      a laparotomy. Four cases were operated on due to suspicion of acute appendicitis
      or peritonitis. Another patient had an emergent operation due to ileo-ileo
      intussusception. CONCLUSIONS: GI manifestations of HSP are common. Colicky
      abdominal pain was the most common GI manifestation of Henoch-Schonlein purpura.
      Some patients may have GI complications, but those requiring surgical
      intervention in our study were rare.

PMID- 15148996
TI  - Comparison of standard white-on-white automated perimetry and short-wavelength
      automated perimetry in early glaucoma patients.
AB  - BACKGROUND: To evaluate the relationship between short-wavelength automated
      perimetry (SWAP) and the standard white-on-white automated perimetry (W-W) in
      detection of early glaucomatous visual field deficits. METHODS: Twenty-four
      patients suspected of having glaucoma and who had experience with automated
      visual field tests were evaluated by SWAP and standard W-W perimetry. Results of
      the mean deviation (MD), pattern standard deviation (PSD), pattern deviation
      probability plot, test reliability, and test time were compared. RESULTS: The
      average MD in the SWAP group was significantly higher than that in the W-W group
      (SWAP: -6.55 db, W-W: -2.69 db, p<0.001). A significant difference also existed
      in PSD between the 2 groups (SWAP: 3.49 db, W-W: 2.40 db, p<0.001). The test time
      was longer in the SWAP group than in the W-W group (SWAP: 15 min, 6 s; W-W: 13
      min, 8 s, p<0.001). There was no significant difference between the 2 groups in
      test reliability or in the number of points that were depressed below the 1% and
      5% sensitivity levels on the pattern deviation probability plot. CONCLUSIONS:
      This study showed that greater MD and PSD were demonstrated with SWAP. The test
      time was longer for SWAP. However, in order to conclude that SWAP is an early
      indicator of glaucomatous damage, longer follow-up and further analyses are
      required.

PMID- 15148995
TI  - Pseudomonas aeruginosa corneal ulcer related to overnight orthokeratology.
AB  - BACKGROUND: Overnight orthokeratology was thought to be a safe and non-invasive
      alternative for low-grade myopia and astigmatism correction. We assessed
      histories, clinical courses, and visual outcomes of the patients with pseudomonal
      keratitis related to overnight orthokeratology. METHODS: The records of six
      patients with pseudomonal keratitis related to overnight orthokeratology were
      reviewed from January 2001 through December 2002. RESULTS: The average age of the
      patients was 13 years. The average period between the time that the patient
      started the overnight orthokeratology program and the onset of infectious
      keratitis was 17 months. All patients presented with painful red eyes. The area
      of the corneal ulcer was central in three, and paracentral in three eyes. The
      corneal infiltrate was small in one eye, and medium in five eyes. The corneal
      scrapings from these six patients revealed Pseudomonas aeruginosa. All patients
      responded well to topical antibiotic treatment. Two of six eyes had a final
      visual acuity within two lines of the pre-infection vision at the last follow-up.
      Four of the eyes examined lost their best-corrected visual acuity due to central
      corneal scar or irregular astigmatism. CONCLUSIONS: Overnight orthokeratology
      contact lens wear has the potential complication of pseudomonal keratitis and may
      cause significant visual impairment.

PMID- 15148997
TI  - Acute retinal necrosis syndrome: clinical manifestations and visual outcomes.
AB  - BACKGROUND: In this paper we attempt to describe the clinical features, visual
      outcomes, and surgical results of patients with acute retinal necrosis (ARN)
      syndrome and elucidate the risk factors for a poor prognosis. We also review the
      methods of treatment. METHODS: This was a retrospective, noncomparative,
      observational study of patients diagnosed with ARN syndrome. Nine patients (11
      eyes) in Chang Gung Memorial Hospital, Kaohsiung from January 1990 to December of
      2002 were enrolled. Blood sera and vitreous specimens were analyzed. Necrosis
      locations and surgical results are described. RESULTS: Bilateral involvement
      occurred in 2 of our 9 patients (2/9, 22.2%). There was no specific relationship
      between age and level of the serum virus antibody. All of our polymerase chain
      reaction data for herpes simplex virus were negative. All 6 eyes of 6 patients
      who underwent surgery for retinal detachment had partial retinal reattachment
      postoperatively. Overall, anatomic success was achieved in 8 eyes (8/11, 72.7%).
      The percentage of eyes with ambulatory visual acuity was 36.3% (4/11), and visual
      acuity was preserved in 27.3% (3/11) at the last visit. CONCLUSIONS: We found
      that retinal necrosis which extended rapidly to the posterior pole was associated
      with a poor visual outcome. Eyes with less than grade II necrosis extension are
      good candidates for prophylactic peripheral retinal photocoagulation. Early
      detection and prompt treatment with acyclovir seems to improve the final visual
      outcome.

PMID- 15148998
TI  - Pulmonary lymphangioleiomyomatosis: a clinicopathological analysis of ten cases.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) of the lung is a very rare disease of
      unknown etiology which occurs particularly in women of childbearing age. So far,
      there have been very few reports of LAM in Taiwan. METHODS: Data on all patients
      with a clinical or pathological diagnosis of LAM in Chang Gung Memorial Hospital
      from 1990 to 2001 were collected from the pathology files or by consultation with
      thoracic surgeons, chest physicians, and radiologists of this institution. Cases
      were confirmed by lung biopsy and high-resolution computed tomographic scanning.
      Clinical data were obtained from patients' charts. Additional immunostaining for
      HMB-45 antigen, estrogen receptor, and progesterone receptor was carried out for
      cases with available paraffin blocks. RESULTS: In total, 10 patients confirmed
      with a diagnosis of LAM and adequate clinical follow-up information were found
      from 1991 to 2001. All were females of fertility age. The follow-up periods
      ranged from 18 to 167 months. Six patients received hormonal therapy. According
      to the pulmonary function tests and clinical symptoms, 6 patients were in stable
      condition and 4 showed slow progression of disease by the time of the last follow
      up. Two patients died after lung transplantation and abdominal surgery for
      retroperitoneal LAM, respectively, at another medical center. CONCLUSIONS: The
      clinicopathological features of our series are similar to those reported from
      other countries. The clinical course was slowly progressive with no significant
      response to hormonal therapy. Lung biopsies are important for a diagnosis, but
      the size and location of the biopsy specimens greatly affect the diagnostic
      reliability.

PMID- 15148999
TI  - Experience with early postoperative feeding after abdominal aortic surgery.
AB  - BACKGROUND: Abdominal aortic surgery is a form of major vascular surgery, which
      traditionally involves long hospital stays and significant postoperative
      morbidity. Experiences with transit ileus are often encountered after the aortic
      surgery. Thus traditional postoperative care involves delayed oral feeding until
      the patients regain their normal bowel activities. This report examines the
      feasibility of early postoperative feeding after abdominal aortic aneurysm (AAA)
      open-repair. METHODS: From May 2002 through May 2003, 10 consecutive patients
      with infrarenal AAA who underwent elective surgical open-repair by the same
      surgeon in our department were reviewed. All of them had been operated upon and
      cared for according to the early feeding postoperative care protocol, which
      comprised of adjuvant epidural anesthesia, postoperative patient controlled
      analgesia, early postoperative feeding and early rehabilitation. The
      postoperative recovery and length of hospital stay were reviewed and analyzed.
      RESULTS: All patients were able to sip water within 1 day postoperatively without
      trouble (Average; 12.4 hours postoperatively). All but one patient was put on
      regular diet within 3 days postoperatively (Average; 2.2 days postoperatively).
      The average postoperative length of stay in hospital was 5.8 days. No patient
      died or had major morbidity. CONCLUSIONS: Early postoperative feeding after open
      repair of abdominal aorta is safe and feasible. The postoperative recovery could
      be improved and the length of stay reduced by simply using adjuvant epidural
      anesthesia during surgery, postoperative epidural patient-controlled analgesia,
      early feeding, early ambulation, and early rehabilitation. The initial success of
      our postoperative recovery program of aortic repair was demonstrated.

PMID- 15149000
TI  - Tracheal injury diagnosed with three-dimensional imaging using multidetector row
      computed tomography.
AB  - Tracheobronchial injury is a rare and serious complication of blunt chest trauma.
      Diagnosis of this injury requires a high index of clinical suspicion. Delay in
      diagnosis is the single most important factor influencing the outcome. Diagnosis
      of this injury may be delayed because of subtle and nonspecific clinical and
      radiological findings and the much more overt clinical signs of other more
      frequently associated injuries. Although the radiographic findings and axial
      computed tomographic (CT) findings of this type of injury have been reported in
      the literature, to the best of our knowledge. the use of 3-dimensional (3D) CT
      has never been reported. We report a case of such an injury demonstrated by
      multiplanar and 3D imaging using a multidetector row computed tomographic
      scanner. A large carinal laceration was clearly depicted on multiplanar and 3D CT
      images.

PMID- 15149001
TI  - Reconstruction using a pericardial tube and ringed Gore-Tex graft for malignant
      superior vena cava syndrome: report of two cases.
AB  - Superior vena cava (SVC) syndrome caused by malignant tumors in the upper
      mediastinum is not uncommon. Radiation therapy or endovascular treatment with
      stenting is the first choice of treatment to relieve symptoms. However, surgical
      treatment may be considered when the less invasive treatment modalities failed.
      In this report, we present two cases of severe symptomatic SVC syndrome as a
      result of invasive thymomas, which were treated successfully using a composite
      graft made by pericardial tube and ringed polytetrafluorethylene (PTFE) graft.
      Symptoms soon subsided after operation. The patients were symptom free at 8
      months and 24 months after the surgical management, respectively. In this report,
      we also reviewed reports in the literature relating to the surgical management in
      SVC syndrome. Based on our limited experience in these cases, we think that
      bypass with pericardial tube could be an effective palliative treatment technique
      offering durable clinical symptom relief for SVC symptoms caused by malignant
      tumors in certain cases.

PMID- 15149002
TI  - Meningitis caused by Pseudallescheria boydii.
AB  - We present a 43-year-old immunocompetent man who developed meningitis caused by
      Pseudallescheria boydii. The patient had no history of near drowning, trauma,
      steroid administration, operations or any other underlying systemic disease. He
      presented with intermittent fever associated with headache, bilateral eye pain,
      and vomiting. Progressive hydrocephalus was noted during the course of the
      disease. Cerebrospinal fluid (CSF) from the ventricular system allowed culture of
      the organism. Although the disease was diagnosed antemortemly, the patient died
      after antifungal treatment. This case is reported because of the unusual
      pathogen, unresponsiveness to amphotericin B combined with 5-fluocytocin, and
      immunocompetence of the patient without any predisposing factors.

PMID- 15149003
TI  - Endoscopic sinus surgery treatment for a huge sinonasal fibroma.
AB  - Fibromas are rare tumors of the nasal cavity, which may result from progressive
      inflammation or fibroblastic proliferation of the nasal mucosa. The tumors are
      usually too small to cause symptoms. We present a 47-year-old woman suffering
      through right nasal obstruction, purulent rhinorrhea and severe headaches for 6
      months. A gray-white, smooth-surfaced, gigantic firm mass occupying the right
      nostril was found in physical examination. Sinus computed tomography revealed 4 x
      3 x 3 cm soft-tissue-density mass in the right nasal cavity and right maxillary
      sinusitis. The huge sinonasal fibroma measuring 4.5 x 3 x 3-cm in the right
      posterior ethmoid sinus, which was successfully endoscopically resected. The
      final diagnosis of fibroma was made histologically, according to light microscopy
      and immunohistochemical stain examinations, which were important for determining
      the patient's treatment. After endoscopic resection, her initial signs and
      symptoms were relieved and no recurrence was noted after 2 years of follow up.

PMID- 15149005
TI  - Consensus on the pre-hospital approach to burns patient management.

PMID- 15149004
TI  - The psychological dimension of chemical, biological, radiological and nuclear
      (CBRN) terrorism.
AB  - Terrorism is an increasing feature of the World Scene. In the UK, our perspective
      has changed from a largely Ireland focused one to a more international view. The
      United States of America are, for the first time, seen as major terrorist
      targets. We are now "at war with terrorism". The medical aspects of terrorism
      have been extensively discussed in this journal and elsewhere, this article
      specifically addresses the psychological consequences of the use of terror
      weapons.

PMID- 15149006
TI  - Clinical findings in 111 ex-Porton Down volunteers.
AB  - OBJECTIVE: To determine whether the health of Porton Down volunteers (PDV) has
      suffered as a result of their participation in medical trials, during which they
      were exposed to single low dose concentrations of chemical warfare agents.
      METHODS: Data were obtained from a self-selected series of ex-Porton Down
      volunteers who attended the MOD's Porton Down Volunteers' Medical Assessment
      Programme (PDVMAP). One hundred and eleven men attended with a mean age of 62
      (range 37-81) years. Information obtained was analysed to determine whether
      clinical diagnoses and symptoms reported had any relationship to chemical
      exposures. RESULTS: The diagnoses were not unusual for UK nationals with a mean
      age of 62 years. The majority of volunteers went to Porton Down in the 1950s and
      then had a mean age of 19. The mean time between volunteers attending Porton Down
      and coming to MAP was 42 years. We found no correlation between chemical
      exposures and later development of established diagnoses, a latent period of 30
      years. CONCLUSION: On a clinical basis, no evidence was found to support the
      hypothesis that participation in Porton Down trials produced any long-term
      adverse health effects or unusual patterns of disease compared to those of the
      general population of the same age.

PMID- 15149007
TI  - Mission creep: an analysis of accident and emergency room activity in a military
      facility in Bosnia-Herzegovina.
AB  - OBJECTIVE: To evaluate accident and emergency (A&E) room activity at a Role 3
      Multinational Integrated Medical Unit (R3 MIMU) facility in Bosnia-Herzegovina.
      METHODS: Retrospective analysis of all patients attending the A&E room from 1st
      October 1999-30th September 2002. RESULTS: 1864 casualties are included in the
      analysis. 52.1% of casualties were Bosnian, 43.8% were military. Mean age of
      casualties was 35.5 years (SD 18.3), range 1-88 years. Traumatic injury was the
      leading cause of presentation (58.1%). Following treatment 66.7% of all cases
      were discharged or returned to unit, with 19.8% admitted to a ward area. During
      the 3 year period there was a 5 fold increase in the number of Bosnian nationals
      treated, this included 80 children (<13 years). CONCLUSION: There has been a
      dramatic increase in Methods A&E use during the period evaluated, Setting of
      study particularly by the local population. The increasing number of locals
      treated, both adult and child, has the potential to undermine the R3 MIMU mission
      and increase dependency within the Bosnian population. A balance is needed to
      ensure the staff and functions of a hospital are maintained whilst preserving the
      capability to deal with an influx of military casualties.

PMID- 15149008
TI  - Cutaneous myiasis due to the Tumbu fly during Operation Keeling.
AB  - Cutaneous myiasis is a temporary infestation of the skin with fly larvae (1). The
      following is a description of a case of cutaneous myiasis caused by the African
      Tumbu fly (Cordylobia anthropophaga). The clinical presentation and treatment of
      this infestation is discussed. A review of the Tumbu fly's lifecycle with
      emphasis on the prevention of the disease in the operational environment is also
      described.

PMID- 15149009
TI  - The personal experiences of the Regimental Aid Post. 1st Bn The Royal Regiment of
      Fusiliers. OP TELIC, Iraq.

PMID- 15149010
TI  - Battlefield Advanced Trauma Life Support (BATLS).
AB  - The vast majority of casualties will only require a common sense approach to
      their preparation for evacuation, by asking simple questions, most problems can
      be identified and resolved prior to the evacuation. Ask? Are aeromed teams
      available to undertake this task? (Contact them). If aeromed teams are
      unavailable but can offer advice, talk to them. Where is the onward destination
      and are they expecting the casualty. (Check). Is the destination suitable for the
      casualty and the aircraft type? (Check). What level of training is required to
      transfer the casualty? (Cbt Med Tech/RGN/MO). Are the appropriate aeromed
      stretchers and harnesses available? (If not get them). Are all the casualty's
      documentation and X-rays available for transportation with the casualty? (Check).
      Does the casualty require a secure airway, intravenous access or fluid
      resuscitation prior to or during flight? (Ideally, the casualty must be as stable
      as possible prior to flight). Are all i.v. lines taped and secure. (Check them).
      Is there sufficient oxygen supply on board for the casualty's(ies) needs to
      complete the journey and cope with delays? This especially applies if the
      ventilator is air or oxygen driven. Has the electrical medical equipment required
      for transportation been cleared for use on the aircraft? (Talk to the aircrew).
      This equipment may be necessary for in-flight monitoring. Even simple tasks such
      as counting a pulse rate using the carotid artery, may be impossible in a
      vibrating airframe. How is the casualty going to be positioned on board the
      aircraft and does the escort have access? (Find out). If the flight is tactical
      and at night, the air-crew may be using night vision goggles, can any light be
      used in the cabin? (On chinooks the crew may be able to provide a blacked out
      area; in other aircraft torches with green filters will have to be used and
      monitoring undertaken by touch. Check the situation with the crew and be prepared
      to adapt). It is very difficult to care for a casualty in the air, particularly
      on a helicopter. It is extremely important to prepare the casualty properly prior
      to the flight. A few extra minutes on the ground preparing the casualty may
      ultimately save their life. However, the tactical situation or the condition of
      the casualty may dictate the scoop and scoot approach, rather than stay and play.

PMID- 15149011
TI  - Plastic surgery.
AB  - The range of casualties treated by the Defence Medical Services in the recent
      Gulf conflict has reaffirmed the important role of plastic surgery within the
      military. This review seeks to highlight some areas of recent innovation and
      improvement within the realms of plastic surgery generally, of which some, such
      as the introduction of Flammacerium and the availability of skin substitutes,
      have direct military relevance.

PMID- 15149012
TI  - Self assessment exercises--Local anaesthesia and sedation.

PMID- 15149013
TI  - Preparation for the MRCS in surgery.
AB  - The MRCS is an examination in a state of flux at the moment and the precise
      requirements of the forthcoming intercollegiate examinations are still awaited,
      but it is expected that many of its features will be directly translated from the
      current arrangements. The keys to success can perhaps be summarised as follows:
      start work well in advance of the examinations, take every opportunity to
      practice your skills and look upon questioning by your seniors as a chance to
      practice rather than an imposition. Finding the textbooks that suit your style of
      learning early on and practising sample questions as often as possible will pay
      dividends.

PMID- 15149014
TI  - Major Jonathan Letterman, Director of Medical Services, Union Army.

PMID- 15149015
TI  - OP TELIC--impact of deployment of personnel with chronic conditions to forward
      areas.

PMID- 15149016
TI  - OP TELIC--impact of deployment of personnel with chronic conditions to forward
      areas.

PMID- 15149017
TI  - No pain, no gain. Part II. A personal conceptualisation of PTSD and post
      traumatic psychological difficulties.

PMID- 15149018
TI  - Pathogenomics of mobile genetic elements of toxigenic bacteria.
AB  - The growing knowledge of genetic diversity and whole genome organization in
      bacteria shows that pathogenicity islands (PAIs) represent a subtype of a more
      general genetic element, termed genomic island (GEI), which is widespread among
      pathogenic and non-pathogenic microbes. These findings mirror the importance of
      horizontal gene transfer, genome reduction and recombination events as
      fundamental mechanisms involved in evolution of bacterial variants. GEIs are part
      of the flexible gene pool and carry selfish genes, but also determinants which
      may be beneficial under certain conditions thus increasing bacterial fitness and
      consequently their survival or transmission. In this review, we focus on the role
      of mobile genetic elements that may also contain toxin-encoding genes for genome
      variability and evolution of bacteria.

PMID- 15149019
TI  - Host cell modulation by human, animal and plant pathogens.
AB  - Members of the alpha-proteobacteria display a broad range of interactions with
      higher eukaryotes. Some are pathogens of humans, such as Rickettsia and
      Bartonella that are associated with diseases like epidemic typhus, trench fever,
      cat scratch disease and bacillary angiomatosis. Others like the Brucella cause
      abortions in pregnant animals. Yet other species have evolved elaborate
      interactions with plants; in this group we find both plant symbionts and
      parasites. Despite radically different host preferences, extreme genome size
      variations and the absence of toxin genes, similarities in survival strategies
      and host cell interactions can be recognized among members of the alpha
      proteobacteria. Here, we review some of these similarities, with a focus on
      strategies for modulation of the host target cell.

PMID- 15149020
TI  - In silico identification of novel bacterial ADP-ribosyltransferases.
AB  - With the advent of the genomic era, identification of bacterial factors involved
      in virulence is a different challenge. Given the vast amount of information
      available on toxins, in terms of sequence and 3D structure, and thanks to the
      growing number of sequenced bacterial genomes, it is possible to proceed by
      homology criteria to predict novel toxins in different microorganisms. ADP
      ribosyltransferases constitute a class of functionally conserved enzymes, which
      display toxic activity in a variety of bacterial pathogens. Since these proteins
      play a key role in pathogenesis, they have been extensively characterized and
      successfully used as vaccine components and mucosal adjuvants. Therefore, the
      application of in silico analyses to identify novel members of this class of
      enzymes represents an important challenge in the genomic era. To address this
      subject, different groups have recently pursued homology-based procedures to
      screen bacterial genomes for novel, yet undiscovered ADP-ribosyltransferases
      (ADPRTs) and have identified more than twenty novel ADPRTs in Gram-positive and
      Gram-negative bacteria. We have developed a novel pattern-based computational
      approach, which, flanked by secondary structure prediction tools, has allowed the
      identification of previously unrecognised putative ADPRTs. One of them,
      identified in Neisseria meningitidis has been extensively characterized and shown
      to possess the predicted enzymatic activity, suggesting a possible role of this
      protein in the virulence of Meningococcus.

PMID- 15149021
TI  - The multi-talented bacterial adenylate cyclases.
AB  - Bacterial pathogens produce a variety of toxins capable of altering the levels of
      cAMP in the cells of infected hosts. Moreover, cAMP is an important signaling
      molecule in many bacterial species, involved in regulation of gene expression in
      response to a variety of environmental stimuli. The genome of the opportunistic
      pathogen Pseudomonas aeruginosa encodes three adenylate cyclases. One of these is
      exoenzyme Y, which is translocated into the host cell via a type III secretion
      system (TTSS). The other two cyclases are CyaA and CyaB, that generate cAMP for
      intracellular signaling, and together with the cognate cAMP-binding protein Vfr,
      control the expression of the TTSS and several virulence factors. Using a mouse
      infection model, it was shown that CyaB, a membrane-bound class III adenylate
      cyclase plays a more prominent role in regulation of TTSS-encoding genes than
      CyaA. Given the wide distribution of the class III adenylate cyclases among
      bacteria, cAMP-dependent regulation of gene expression may have evolved as a
      conserved mechanism for sensing environmental signals ranging from nutritional
      content of the surrounding media to the presence of host tissues.

PMID- 15149022
TI  - Pathways followed by protein toxins into cells.
AB  - A number of protein toxins have an enzymatically active part, which is able to
      modify a cytosolic target. Some of these toxins, for instance ricin, Shiga toxin
      and cholera toxin, which we will focus on in this article, exert their effect on
      cells by first binding to the cell surface, then they are endocytosed, and
      subsequently they are transported retrogradely all the way to the ER before
      translocation of the enzymatically active part to the cytosol. Thus, studies of
      these toxins can provide information about pathways of intracellular transport.
      Retrograde transport to the Golgi and the ER seems to be dependent not only on
      different Rab and SNARE proteins, but also on cytosolic calcium,
      phosphatidylinositol 3-kinase and cholesterol. Comparison of the three toxins
      reveals differences indicating the presence of more than one pathway between
      early endosomes and the Golgi apparatus or, alternatively, that transport of
      different toxin-receptor complexes present in a certain subcompartment is
      differentially regulated.

PMID- 15149023
TI  - Retrograde transport of cholera toxin into the ER of host cells.
AB  - Cholera toxin moves from the plasma membrane to the ER of host cells to cause
      disease. Here we discuss recent studies on the mechanism of transport from plasma
      membrane to the ER and on the reactions that unfold and retrotranslocate a
      portion of the toxin to the cytosol where toxicity is induced.

PMID- 15149024
TI  - Analysing the action of bacterial toxins in living cells with fluorescence
      resonance energy transfer (FRET).
AB  - Bacterial toxins represent small molecules produced by microorganisms. Different
      toxins act on specific target molecules in mammalian cells. Once discovered,
      bacterial toxins have been providing tools to study cellular functions and often
      helped the dissection of complex cellular pathways, e.g. endocytic or secretory
      trafficking or signal transduction, by virtue of the fact that they either block
      or activate their specific cellular target molecules. Purified bacterial toxins
      have also allowed to address many basic biological questions and have provided
      tools for in vitro and in vivo experimental approaches in many fields of modern
      biology. The understanding of how bacterial toxins act in living cells often
      depends on our ability to visualize the trafficking and signaling pathways of
      these molecules. Fluorescence microscopy and other imaging tools are essential to
      provide insights into the functional changes induced by these pathogens at the
      level of individual host cells or single target proteins. Inside a single cell we
      can measure and quantify the effects of bacterial toxins on specific cellular
      proteins by microscopic and spectroscopic techniques. Fluorescence resonance
      energy transfer (FRET) is a high-resolution technique that allows to study
      protein-protein interactions. FRET can provide distance information in the range
      of 3- 7 nm between fluorescently labeled bacterial proteins in the live cell and
      cellular target proteins expressed as chimeras with green fluorescent protein
      (GFP), or spectrally shifted variants thereof. The purpose of this review is to
      introduce readers to the main experimental setups for analyses of protein-protein
      interactions using FRET as well as some applications.

PMID- 15149025
TI  - The pasteurella multocida toxin interacts with signalling pathways to perturb
      cell growth and differentiation.
AB  - Some years ago we showed that the Pasteurella multocida toxin (PMT) is a potent
      mitogen for cells in culture. It is an intracellularly acting toxin that
      stimulates several signal transduction pathways. The heterotrimeric G-protein,
      Gq, is stimulated, which in turn causes activation of protein kinase C and an
      increase in inositol trisphosphates. The Rho GTPase is also activated, leading
      via the Rho kinase, to activation of the focal adhesion kinase and to
      cytoskeletal rearrangements. Analysis of the PMT sequence suggested the presence
      of three domains that encode receptor binding, translocation and catalytic
      domains. The location of all three domains has been confirmed directly.
      Competitive binding assays confirmed that the N-terminus of PMT encoded the
      receptor-binding domain, while cytoplasmic microinjection of expressed PMT
      fragments identified the location of the C-terminal catalytic domain. Recently,
      we have demonstrated the presence of key amino acids that affect membrane
      insertion within the putative transmembrane domain. Several lines of evidence
      suggest that PMT activates Galphaq, and that this is one potential molecular
      target for the toxin. Galphaq is known to be tyrosine phosphorylated when
      activated normally via a G-protein-coupled receptor (GPCR), and it has been
      suggested that this is an essential part of the activation process. We have shown
      that PMT induces Galphaq tyrosine phosphorylation, but that this is not essential
      for activation of the G-protein. Furthermore, a totally inactive mutant of PMT
      stimulates Galpha phosphorylation without leading to its activation.
      Phosphorylation of Galphaq triggered by the inactive mutant potentiates
      activation of Gq via a GPCR, demonstrating that phosphorylation of Gq cannot lead
      to receptor uncoupling. Natural or experimental infection of animals with
      toxigenic P. multocida, or injection with purified recombinant PMT causes loss of
      nasal turbinate bone. The effects on bone have been analysed in vitro using
      cultures of osteoblasts--cells that lay down bone. PMT blocks the formation of
      mature calcified bone nodules and the expression of differentiation markers such
      as CBFA-1, alkaline phosphatase and osteocalcin. These effects can be partially
      prevented by inhibitors of Rho or Rho kinase function, implicating this pathway
      in osteoblast differentiation. Indeed, inhibitors of Rho stimulate the formation
      of bone nodules in vitro. In summary, PMT is a novel toxin that acts via
      signalling pathways to promote proliferation in many cells, while specifically
      inhibiting differentiation in osteoblast cells.

PMID- 15149027
TI  - Molecular and cell biology of Legionella pneumophila.
AB  - Legionella pneumophila is a facultative intracellular pathogen that can replicate
      within phagocytic host cells such as protozoa and macrophages. Evasion of
      phagocytic killing is mediated by the type IV Dot/Icm secretion system, which
      exports bacterial effectors that modulate biogenesis of the phagosome to evade
      endocytic fusion and also to intercept vesicles derived from the endoplasmic
      reticulum. Bacterial replication is associated with activation of caspase-3 in
      infected macrophages and is culminated in apoptosis and pore formation-mediated
      cytolysis of the host.

PMID- 15149026
TI  - E. coli CNF1 toxin: a two-in-one system for host-cell invasion.
AB  - The cytotoxic necrotizing factor-1 (CNF1), a bacterial toxin of uropathogenic
      bacteria (UPEC), hijacks cellular Rho proteins of the Ras GTPase super-family.
      Recently, we have made three important findings. First, we have established that,
      following Rho protein activation by deamidation, these cellular proteins are
      ubiquitylated and degraded by the proteasome. Second, the low level of activated
      Rho proteins which results from the dual molecular mechanism of action of CNF1
      (Rho protein activation followed by their degradation), confers high invasive
      properties to UPECs. Finally, we have reported that ubiquitylation and
      degradation of Rac is lost in HEp-2 carcinoma cells, thereby suggesting a
      possible link between Rho protein ubiquitylation and tumor progression.

PMID- 15149028
TI  - Superantigens: structure-function relationships.
AB  - Superantigens are a class of highly potent immuno-stimulatory molecules produced
      by Staphylococcus aureus and Streptococcus pyogenes. These toxins possess the
      unique ability to interact simultaneously with MHC class II molecules and T-cell
      receptors, forming a trimolecular complex that induces profound T-cell
      proliferation. The resultant massive cytokine release causes epithelial damage
      and leads to capillary leak and hypotension. The staphylococcal superantigens are
      designated staphylococcal enterotoxins A, B, C (and antigenic variants), D, E,
      and the recently discovered enterotoxins G to Q, and toxic shock syndrome toxin
      1. The streptococcal superantigens include the pyrogenic exotoxins A (and
      antigenic variants), C, G-J, SMEZ, and SSA. Superantigens are implicated in
      several diseases including toxic shock syndrome, scarlet fever and food
      poisoning; and their function appears primarily to debilitate the host
      sufficiently to permit the causation of disease. Structural studies over the last
      10 years have provided a great deal of information regarding the complex
      interactions of these molecules with their receptors. This, combined with the
      wealth of new information from genomics initiatives, have shown that, despite
      their common molecular architecture, superantigens are able to crosslink MHC
      class II molecules and T-cell receptors by a variety of subtly different ways
      through the use of various structural regions within each toxin.

PMID- 15149030
TI  - Exploitation of host cells by Burkholderia pseudomallei.
AB  - Intracellular bacterial pathogens have evolved mechanisms to enter and exit
      eukaryotic cells using the power of actin polymerisation and to subvert the
      activity of cellular enzymes and signal transduction pathways. The proteins
      deployed by bacteria to subvert cellular processes often mimic eukaryotic
      proteins in their structure or function. Studies on the exploitation of host
      cells by the facultative intracellular pathogen Burkholderia pseudomallei are
      providing novel insights into the pathogenesis of melioidosis, a serious invasive
      disease of animals and humans that is endemic in tropical and subtropical areas.
      B. pseudomallei can invade epithelial cells, survive and proliferate inside
      phagocytes, escape from endocytic vesicles, form actin-based membrane protrusions
      and induce host cell fusion. Here we review current understanding of the
      molecular mechanisms underlying these processes.

PMID- 15149029
TI  - Novel activities of the Helicobacter pylori vacuolating cytotoxin: from
      epithelial cells towards the immune system.
AB  - H. pylori has developed a unique set of virulence factors, which allow its
      survival in a unique ecological niche, the human stomach. The vacuolating
      cytotoxin (VacA) and the cytotoxin-associated antigen (CagA) are major bacterial
      factors involved in modulating the host. VacA, so far mainly regarded as a
      cytotoxin for the gastric epithelial cell layer, apparently has profound effects
      in modulating the immune response. In this review we discuss some of the
      classical effects of VacA, such as cell vacuolation, and compare them with more
      recently identified mechanisms of VacA on immune cells.

PMID- 15149031
TI  - Clostridium botulinum C2 toxin--new insights into the cellular up-take of the
      actin-ADP-ribosylating toxin.
AB  - Clostridium botulinum C2 toxin is a member of the family of binary actin-ADP
      ribosylating toxins. It consists of the enzyme component C2I, and the separated
      binding/translocation component C2II. Proteolytically activated C2II forms
      heptamers and binds to a carbohydrate cell surface receptor. After attachment of
      C2I, the toxin complex is endocytosed to reach early endosomes. At low pH of
      endosomes, C2II-heptamers insert into the membrane, form pores and deliver C2I
      into the cytosol. Here, C2I ADP-ribosylates actin at Arg177 to block actin
      polymerization and to induce depolymerization of actin filaments. The mini-review
      describes main properties of C2 toxin and discusses new findings on the
      involvement of chaperones in the up-take process of the toxin.

PMID- 15149032
TI  - Inverted pathogenicity: the use of pathogen-specific molecular mechanisms for
      prevention or therapy of disease.
AB  - The term "inverted pathogenicity" stands for the exploitation of microbial
      toxins, virulence factors and cellular mechanisms for preventive or therapeutic
      purposes. This mini-review will focus on the major pathogenicity concept of
      Salmonella and Yersinia and how to use its underlying molecular principle for the
      development of a novel vaccination strategy. Both bacterial species employ a type
      III secretion system which mediates secretion and direct delivery (translocation)
      of antihost factors into the cytosol of eukaryotic cells. One of the best studied
      type III effector proteins is the 25-kDa Yersinia outer protein E (YopE). During
      the interaction of Yersinia with professional phagocytes, YopE translocation
      disturbs eukaryotic cytoskeleton dynamics and inhibits phagocytosis. YopE is a
      GTPase-activating protein that is active towards G proteins from the Rho family.
      Fusion of the N-terminal 138 amino acids of YopE comprising the translocation
      domain of the type III molecule to listeriolysin O (LLO) or p60 of Listeria
      monocytogenes results in hybrid proteins that are engaged and translocated by
      both Yersinia and Salmonella type III secretion systems. Oral immunization of
      mice with attenuated Yersinia or Salmonella vaccine strains expressing
      translocated chimeric YopE leads to pronounced LLO- or p60-peptide-specific CD8 T
      cell responses that confer protective immunity. Surprisingly, cytosolic delivery
      of YopE/LLO by Yersinia also results in LLO-specific CD4 T-cell priming.

PMID- 15149034
TI  - Recombinant immunotoxins for treating cancer.
AB  - Recombinant immunotoxins are antibody-toxin chimeric molecules that kill cancer
      cells via binding to a surface antigen, internalization and delivery of the toxin
      moiety to the cell cytosol. In the cytosol, toxins catalytically inhibit a
      critical cell function and cause cell death. The antibody portion of the chimera
      targets antigens that are expressed preferentially on the surface of cancer
      cells. Truncated versions of either diphtheria toxin (DT) or Pseudomonas exotoxin
      (PE) can be used to construct fusions with cDNAs encoding antibody fragments or
      cell-binding ligands. Recombinant immunotoxins are routinely produced in E. coli
      and purified using standard chromatographic methods. Before they can be evaluated
      for anticancer activity in humans, recombinant immunotoxins undergo extensive
      preclinical testing. Immunotoxins must demonstrate cell-killing activity in
      tissue culture, antitumor activity in an animal model and have favorable
      pharmacokinetic and toxicity profiles. Candidate molecules with favorable
      characteristics are then evaluated in clinical trials. Here we report on the
      initial evaluation of BL22, a recombinant immunotoxin targeted to CD22 expressed
      on the surface of B-cell malignancies.

PMID- 15149033
TI  - The adenylate cyclase toxin from Bordetella pertussis--a novel promising vehicle
      for antigen delivery to dendritic cells.
AB  - Bordetella pertussis secretes an adenylate cyclase toxin (CyaA or ACT) that
      targets primarily cells expressing the alphaMbeta2 integrin (CD11b/CD18)
      receptor. This toxin can deliver its N-terminal catalytic AC domain (400 amino
      acid residues) into the cytosol directly across the cytoplasmic membrane. Various
      heterologous CD8+, as well as CD4+ T-cell epitopes have been engineered into
      genetically detoxified CyaA and the resulting toxoids were successfully used as
      vectors for delivery of inserted epitopes into antigen-presenting cells. Upon
      processing and presentation, these recombinant CyaAs trigger specific MHC class I
      and/or class II-restricted T-cell responses both in vitro and in vivo.

PMID- 15149036
TI  - The multiple cellular activities of the VacA cytotoxin of Helicobacter pylori.
AB  - Helicobacter pylori has elaborated a unique set of virulence factors that allow
      it to colonize the stomach wall. These factors include urease, helicoidal shape,
      flagella, adhesion and pro-inflammatory molecules. Here we discuss the molecular
      and cellular mechanisms of action of the vacuolating cytotoxin VacA. Its
      activities are discussed in terms of tissue alterations which promote the release
      of nutrients necessary to the growth and survival of the bacterium in its
      nutrient-poor ecological niche. This toxin also shows some pro-inflammatory and
      immunosuppressive activities which may be functional to the establishment of a
      chronic type of inflammation.

PMID- 15149035
TI  - Bordetella pertussis from functional genomics to intranasal vaccination.
AB  - Whooping cough still represents a major health problem, despite the use of
      effective vaccines for several decades. Being classically a typical childhood
      disease, whooping cough in young adults is now more common than it used to be,
      suggesting that protection after vaccination wanes during adolescence. As an
      alternative to the current vaccines, we wish to develop live attenuated vaccines
      to be delivered by the nasal route, such as to mimic the natural route of
      infection and to induce long lasting immunity. Bordetella pertussis, the
      etiological agent of whooping cough, produces a number of virulence factors,
      including toxins. Its recently determined genome sequence makes it now possible
      to apply functional genomics, such as transcriptomics and systematic knock-out
      mutagenesis. The expression of most known B. pertussis virulence genes is
      controlled by the two-component system BvgA/S. DNA microarray analyses have led
      to the identification of novel genes in the BvgA/S regulon, some of which are
      activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes
      appear to be differentially modulated by nicotinic acid and MgSO4, both known to
      modulate the expression of BvgA/S-regulated genes. Among others, the functional
      genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA
      and hotB (for 'homolog of toxin'), the products of which show high sequence
      similarities to pertussis toxin subunits. The identification of the full array of
      virulence factors, as well as an integrated understanding of the bacterial
      physiology should allow us to design attenuated B. pertussis strains useful for
      intranasal vaccination. A first generation of attenuated strains has already
      shown full protection in mice after a single intranasal administration. Such
      strains may also serve as vaccine carriers for heterologous antigens, in order to
      vaccinate against several different pathogens simultaneously.

PMID- 15149037
TI  - Pore worms: using Caenorhabditis elegans to study how bacterial toxins interact
      with their target host.
AB  - The interaction of pathogenic bacteria with a target host is regulated both by
      bacterial virulence factors and by host components that either protect the host
      or that promote pathogenesis. The soil nematode Caenorhabditis elegans is a host
      for a number of bacterial pathogens, as briefly reviewed here. Bacillus
      thuringiensis (Bt) is a pathogenic bacteria that C. elegans is likely to
      encounter naturally in the soil. The pore-forming Crystal (Cry) toxins made by Bt
      are recognized as the dominant virulence factor in this host-pathogen
      interaction. Forward genetic screens for C. elegans mutants resistant to the Cry
      toxin, Cry5B, have identified a host carbohydrate structure that promotes
      pathogenesis. Data suggest this structure is likely to be a Cry5B receptor
      expressed in the host intestine. This finding is discussed in light of other
      carbohydrate receptors for bacterial toxins. To investigate host-toxin
      interactions on a global level, the response of C. elegans to the pore-forming
      Cry5B is also being investigated by gene transcription profiling (microarrays).
      These data are beginning to reveal a diverse intracellular response to toxin
      exposure. To put these investigations in perspective, host responses to other
      pore-forming toxins are discussed. Investigations with Cry5B in C. elegans show a
      promising beginning in helping to elucidate host-toxin and host-pathogen
      interactions.

PMID- 15149038
TI  - Enterococcal cytolysin: activities and association with other virulence traits in
      a pathogenicity island.
AB  - Enterococcal cytolysin is a structurally novel bacterial toxin expressed by some
      strains of E. faecalis and is distantly related to the class of bacteriocins
      known as lantibiotics. The cytolysin can be encoded by large pheromone-responsive
      plasmids, or on the chromosome within pathogenicity island. It is produced by a
      complex process that involves the products of eight genes, designated cylR1,
      cylR2, cylLL, cylLS, cylM, cylB, cylA, and cylI. The cytolysin toxin, maturation
      and regulatory genes are organized into two divergent transcripts: a structural
      transcript cylLLLSMBAI, and a regulatory transcript cylR1R2. The active cytolysin
      subunits, CylLL" and CylLS", are synthesized ribosomally as non-identical
      peptides, post-translationally modified, then secreted and activated. The
      cytolysin operon is repressed by the activities of two proteins, CylR1 and CylR2,
      and derepressed by a quorum-sensing process involving secreted autoinducer
      CylLS". The cytolysin operon within the E. faecalis pathogenicity island is
      associated with other virulence determinants, including aggregation substance and
      enterococcal surface protein, Esp.

PMID- 15149039
TI  - In vivo Bacillus anthracis gene expression requires PagR as an intermediate
      effector of the AtxA signalling cascade.
AB  - Transcription of the major Bacillus anthracis virulence genes is triggered by
      CO2, a signal mimicking the host environment. A 182-kb plasmid, pXO1, carries the
      anthrax toxin genes and the genes responsible for their regulation of
      transcription, namely atxA and, pagR, the second gene of the pag operon. AtxA has
      major effects on the physiology of B. anthracis. It coordinates the transcription
      activation of the toxin genes with that of the capsule biosynthetic enzyme
      operon, located on the second virulence plasmid, pXO2. In rich medium, B.
      anthracis synthesises alternatively two S-layer proteins (Sap and EA1). An
      exponential phase "Sap-layer" is subsequently replaced by a stationary phase "EA1
      layer". S-layer gene transcription is controlled by alternative sigma factors and
      by Sap acting as a transcriptional repressor of eag. Furthermore, in vitro in
      presence of CO2 and in vivo, AtxA is part of the sap and eag regulatory network.
      Only eag is significantly expressed in these conditions and this is due to AtxA
      activating eag and repressing sap transcription. PagR, and not AtxA itself, is
      the direct effector of this regulation by binding to sap and eag promoter
      regions. Therefore, PagR mediates the effect of AtxA on eag and sap and is the
      most downstream element of a signalling cascade initiated by AtxA. Taken
      together, these results indicate that the B. anthracis transcriptional regulator
      AtxA is controlling the synthesis of the three toxin components and of the
      surface elements (capsule and S-layer). Thus, AtxA is a master regulator that
      coordinates the response to host signals by orchestrating positive and negative
      controls over genes located on all genetic elements.

PMID- 15149040
TI  - Comparisons of the dust/smoke particulate that settled inside the surrounding
      buildings and outside on the streets of southern New York City after the collapse
      of the World Trade Center, September 11, 2001.
AB  - The collapse of the World Trade Center (WTC) on September 11, 2001, generated
      large amounts of dust and smoke that settled in the surrounding indoor and
      outdoor environments in southern Manhattan. Sixteen dust samples were collected
      from undisturbed locations inside two uncleaned buildings that were adjacent to
      Ground Zero. These samples were analyzed for morphology, metals, and organic
      compounds, and the results were compared with the previously reported outdoor WTC
      dust/smoke results. We also analyzed seven additional dust samples provided by
      residents in the local neighborhoods. The morphologic analyses showed that the
      indoor WTC dust/smoke samples were similar to the outdoor WTC dust/smoke samples
      in composition and characteristics but with more than 50% mass in the <53-microm
      size fraction. This was in contrast to the outdoor samples that contained >50% of
      mass above >53 microm. Elemental analyses also showed the similarities, but at
      lower concentrations. Organic compounds present in the outdoor samples were also
      detected in the indoor samples. Conversely, the resident-provided convenience
      dust samples were different from either the WTC indoor or outdoor samples in
      composition and pH, indicating that they were not WTC-affected locations. In
      summary, the indoor dust/smoke was similar in concentration to the outdoor
      dust/smoke but had a greater percentage of mass <53 microm in diameter.

PMID- 15149042
TI  - Roadside particle number distributions and relationships between number
      concentrations, meteorology, and traffic along a northern California freeway.
AB  - Particle number distributions were measured simultaneously upwind and downwind of
      a suburban-agricultural freeway to determine relationships with traffic and
      meteorological parameters. Average traffic volumes were 6330 vehicles/hr with 10%
      heavy-duty vehicles, and volumes were higher in July than November. Most downwind
      particle number distributions were bimodal, with a primary mode at approximately
      10-25 nm, indicating that newly formed particles were sampled. Total downwind 6
      237 nm particle number concentrations (Ntot) ranged from 9.3 x 10(3) to 2.5 x
      10(5) cm(-3), with higher daily average concentrations in November compared with
      July. Ntot correlated with wind speed, temperature, and relative humidity. Upwind
      photochemically initiated nucleation likely led to elevated background
      nanoparticle concentrations in July, as evidenced by increasing upwind
      distribution modal diameter with increasing temperature and a strong correlation
      between upwind Ntot and solar radiation. Also in summer, Ntot showed stronger
      correlation with heavy-duty vehicle volumes than wind speed, temperature, and
      relative humidity. These results indicate the importance of measuring background
      particle size distributions simultaneously with roadside distributions. There may
      be a minimum vehicle volume from which useful real-world vehicle particle number
      distributions can be measured at roadside, even when collecting samples within 10
      m of the traveled lanes.

PMID- 15149041
TI  - Remediation of MTBE from drinking water: air stripping followed by off-gas
      adsorption.
AB  - The widespread use of methyl tertiary butyl ether (MTBE) as an oxygenate in
      gasoline has resulted in the contamination of a large number of ground and
      surface water sources. Even though air stripping has been proven to be an
      effective treatment technology for MTBE removal, off-gas treatment often is
      required in conjunction with it. This study evaluated the combined treatment
      technologies of air stripping followed by off-gas adsorption on a pilot scale for
      the treatment of MTBE-contaminated water. The effect of air/water ratios on the
      treatment efficiency was studied, and the mass transfer coefficient was
      determined. Air/water ratios of 105:1, 151:1, 177:1, 190:1, 202:1, and 206:1 were
      used, and a treatment efficiency of >99% was achieved for all the runs conducted.
      The depth of packing required to achieve maximum treatment efficiency decreased
      with increasing air/water ratio. Relative humidity (RH) impacts on the MTBE
      adsorption capacity of a granular activated carbon (GAC) and carbonaceous resin
      were determined from pilot plant studies. Breakthrough profiles obtained from the
      pilot plant studies conducted at 20, 30, and 50% RH indicated that GAC has a
      higher adsorptive capacity than resin. The adsorptive capacity of GAC decreased
      with increasing RH, whereas RH did not impact the resin adsorptive capacity.

PMID- 15149043
TI  - Emission characteristics of PCDD/Fs, PCBs, chlorobenzenes, chlorophenols, and
      PAHs from polyvinylchloride combustion at various temperatures.
AB  - The effect of temperature on polyvinylchloride (PVC) combustion using a
      downstream tubular furnace was investigated for the formation of polycylcic
      aromatic hydrocarbons (PAHs) and chlorinated compounds. As the temperature
      increased, higher levels of PAHs were generated. Chlorinated compounds reached a
      peak at 600 degrees C, with low emissions recorded at 300 and 900 degrees C.
      There was a close correlation (R2 = 0.97) among polychlorinated biphenyls (PCBs),
      hexachlorobenzene, pentachlorobenzene, and polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/Fs). PAHs at all temperatures were analyzed
      in the gas phase. PCDD/Fs and PCBs were emitted as a solid phase at 300 and 600
      degrees C and as a gas phase at 900 degrees C. For some PAHs, chlorobenzenes, and
      PCDD/Fs, a mathematical equation between the gas and solid phase and the
      reciprocal temperature in semilog proportion was derived. The proposed equation,
      which is log (amount in gas phase/amount in solid phase) = -A/T + B, where T is
      the temperature of the furnace and A and B are constants, for these species
      relating their gas/solid distributions showed a good relationship.

PMID- 15149044
TI  - Contribution of vehicle emissions from an attached garage to residential indoor
      air pollution levels.
AB  - The infiltration of vehicle emissions into a house from the attached garage was
      studied for 16 homes of differing designs using the same extensively
      characterized vehicle at each home. Before the in-home measurement program, the
      cold-start and hot-start tailpipe emissions and hot-soak evaporative emissions
      from a 1993 Buick Regal were measured using standard vehicle emissions
      measurement methods. The emissions were chemically characterized for methane,
      nonmethane hydrocarbons (NMHC), and carbonyl compounds. The in-home measurements
      occurred over two winter seasons (1997-1998 and 1998-1999) in Ottawa, Ontario,
      Canada. Samples of indoor air and garage atmosphere were characterized for carbon
      monoxide, carbon dioxide, methane, NMHC, and carbonyl compounds. During the
      second year, real-time measurements of carbon, carbon dioxide, and total
      hydrocarbons were made to determine when and for how long the emissions plume
      infiltrates the house. Chemical mass balance modeling results using 31 NMHC
      species suggest that between 9 and 71% of the concentrations measured in the
      house during the hot-soak test and between 13 and 85% of the concentrations
      measured in the house during the cold-start test could be attributed to vehicle
      emissions infiltrating from the garage. In contrast, increases in carbonyl
      compound concentrations caused by the vehicle were difficult to detect above the
      already significant levels found in the houses.

PMID- 15149045
TI  - Aerosol ion characteristics during the Big Bend Regional Aerosol and Visibility
      Observational study.
AB  - The ionic compositions of particulate matter with aerodynamic diameter < or = 2.5
      microm (PM2.5) and size-resolved aerosol particles were measured in Big Bend
      National Park, Texas, during the 1999 Big Bend Regional Aerosol and Visibility
      Observational study. The ionic composition of PM2.5 aerosol was dominated by
      sulfate (SO4(2-)) and ammonium (NH4+). Daily average SO4(2-) and NH4+
      concentrations were strongly correlated (R2 = 0.94). The molar ratio of NH4+ to
      SO4(2-) averaged 1.54, consistent with concurrent measurements of aerosol
      acidity. The aerosol was observed to be comprised of a submicron fine mode
      consisting primarily of ammoniated SO4(2-) and a coarse particle mode containing
      nitrate (NO3-). The NO3- appears to be primarily associated with sea salt
      particles where chloride has been replaced by NO3-, although formation of calcium
      nitrate (Ca(NO3)2) is important, too, on several days. Size-resolved aerosol
      composition results reveal that a size cut in particulate matter with aerodynamic
      diameter < or = 1 microm would have provided a much better separation of fine and
      coarse aerosol modes than the standard PM2.5 size cut utilized for the study.
      Although considerable nitric acid exists in the gas phase at Big Bend, the
      aerosol is sufficiently acidic and temperatures sufficiently high that even
      significant future reductions in PM2.5 SO4(2-) are unlikely to be offset by
      formation of particulate ammonium nitrate in summer or fall.

PMID- 15149046
TI  - Method for reporting in-use vehicle fuel consumption and carbon dioxide emissions
      from a fast-pass transient inspection.
AB  - A method has been developed that allows reporting of the fuel consumption and
      carbon dioxide (CO2) emissions for in-use vehicles from a fast-pass transient
      (IM240) inspection. The major technical obstacle to reporting CO2 emission rate
      and fuel consumption is that inspection and maintenance tests do not all use a
      standardized test duration or test method. The method is able to project full
      duration fuel consumption from IM240 tests that actually fast-passed as early as
      just 30 sec from starting the test. It is based on basic considerations of the
      work done in driving the inspection cycle, with additional empirical adjustments.
      The initial application examined the differences between passing and failing
      inspections, and this did confirm that there are significant differences.

PMID- 15149047
TI  - Design scenario for the radioisotopic estimation of the biogenic component of
      airborne particles.
AB  - An experimental design is described to estimate the fraction of secondary fine
      particle from the biogenic component of volatile organic compounds (VOCs) in the
      atmosphere using radiocarbon isotopic abundance ratios. The method distinguishes
      between "modern" carbon (C), and "old" C of primary and secondary origins based
      on three components, condensed-phase organic carbon (OC), semi-volatile
      particulate compounds (SVOCs), and VOCs. The method depends on interpretation of
      diurnal and seasonal variation in OC, SVOC, and VOC concentrations. Sampling
      employs a filter-denuder unit, which collects the three C components for isotopic
      analysis. The samples are collected repetitively for a daily sequence of the same
      hourly intervals covering diurnal periods with similar meteorological conditions.
      Collected C is thermally treated to separate OC from black carbon on filters and
      VOCs or SVOCs from adsorbents, with all four fractions individually oxidized to
      carbon dioxide to determine the radiocarbon content by accelerator mass
      spectrometry. Using C isotope abundance, the data are interpreted for fractions
      of primary modern C and secondary modern C as estimated from averaging diurnal
      and seasonal variations in the concentration data. As support for interpretation,
      samples of OC, SVOCs, and VOCs would be analyzed for speciation to identify
      source indicator species present.

PMID- 15149048
TI  - Development of a hazardous air pollutants monitoring program using the Data
      Quality Objectives process.
AB  - To effectively reduce the environmental compliance costs associated with meeting
      hazardous air pollutant emission requirements, the U.S. Environmental Protection
      Agency's Data Quality Objective (DQO) process has been proposed as a suitable
      framework for establishing a defensible monitoring program. Through the use of a
      hazardous materials pilot study, the variability in the composite vapor pressure
      for regulated handwipe cleaning solvents was established. These results served as
      inputs to the DQO process, which identified that for facility decision-makers to
      claim with a 99% confidence level that the facility is in compliance with the
      National Emission Standards for Hazardous Air Pollutants (NESHAP), a minimum of
      12 handwipe cleaning solvent compliance samples (taken at random every 6 months)
      must have a composite vapor pressure equal to or below the regulatory limit of 45
      mmHg at 20 degrees C. Implementation of the DQO-based compliance-sampling plan
      eliminates the need for an affected facility to sample all regulated handwipe
      cleaning solvents while still maintaining a reasonably high level of confidence
      in the compliance status of its regulated sources. The approach described for
      designing a defensible compliance sampling plan can be extended to other aspects
      of the aerospace NESHAP rule, including compliance sampling for surface coating,
      chemical depainting, and hazardous waste disposal.

PMID- 15149049
TI  - Measurement and analysis of the relationship between ammonia, acid gases, and
      fine particles in eastern North Carolina.
AB  - An annular denuder system, which consisted of a cyclone separator; two diffusion
      denuders coated with sodium carbonate and citric acid, respectively; and a filter
      pack consisting of Teflon and nylon filters in series, was used to measure acid
      gases, ammonia (NH3), and fine particles in the atmosphere from April 1998 to
      March 1999 in eastern North Carolina (i.e., an NH3-rich environment). The sodium
      carbonate denuders yielded average acid gas concentrations of 0.23 microg/m3
      hydrochloric acid (standard deviation [SD] +/- 0.2 microg/m3); 1.14 microg/m3
      nitric acid (SD +/- 0.81 microg/m3), and 1.61 microg/m3 sulfuric acid (SD +/-
      1.58 microg/m3). The citric acid denuders yielded an average concentration of
      17.89 microg/m3 NH3 (SD +/- 15.03 microg/m3). The filters yielded average fine
      aerosol concentrations of 1.64 microg/m3 ammonium (NH4+; SD +/- 1.26 microg/m3);
      0.26 microg/m3 chloride (SD +/- 0.69 microg/m3), 1.92 microg/m3 nitrate (SD +/-
      1.09 microg/m3), and 3.18 microg/m3 sulfate (SO4(2-); SD +/- 3.12 microg/m3).
      From seasonal variation, the measured particulates (NH4+, SO4(2-), and nitrate)
      showed larger peak concentrations during summer, suggesting that the gas-to
      particle conversion was efficient during summer. The aerosol fraction in this
      study area indicated the domination of ammonium sulfate particles because of the
      local abundance of NH3, and the long-range transport of SO4(2-) based on back
      trajectory analysis. Relative humidity effects on gas-to-particle conversion
      processes were analyzed by particulate NH4+ concentration originally formed from
      the neutralization processes with the secondary pollutants in the atmosphere.

PMID- 15149050
TI  - Navigating the future of critical care.

PMID- 15149051
TI  - Professionalism.

PMID- 15149052
TI  - Visiting preferences of patients in the intensive care unit and in a complex care
      medical unit.
AB  - BACKGROUND: Within the challenging healthcare environment are nurses, patients,
      and patients' families. Families want proximity to their loved ones, but the
      benefits of such proximity depend on patients' conditions and family-patient
      dynamics. OBJECTIVES: To describe patients' preferences for family visiting in an
      intensive care unit and a complex care medical unit. METHODS: Sixty-two patients
      participated in a structured interview that assessed patients' preferences for
      visiting, stressors and benefits of visiting, and patients' perceived
      satisfaction with hospital guidelines for visiting. RESULTS: Patients in both
      units rated visiting as a nonstressful experience because visitors offered
      moderate levels of reassurance, comfort, and calming. Patients in the intensive
      care unit worried more about their families than did patients in the complex care
      medical unit but valued the fact that visitors could interpret information for
      the patients while providing information to assist the nurse in understanding the
      patients. Patients in the intensive care unit were more satisfied with visiting
      practices than were patients in the complex care medical unit, although both
      groups preferred visits of 35 to 55 minutes, 3 to 4 times a day, and with usually
      no more than 3 visitors. CONCLUSIONS: These data provide the input of patients in
      the ongoing discussion of visiting practices in both intensive care units and
      complex care medical units. Patients were very satisfied with a visiting
      guideline that is flexible enough to meet their needs and those of their family
      members.

PMID- 15149053
TI  - Desquamative interstitial pneumonia masquerading as acute life-threatening
      pulmonary embolism.

PMID- 15149054
TI  - Critical care nurses' perceptions of futile care and its effect on burnout.
AB  - BACKGROUND: Nurses' perceptions of futile care may lead to emotional exhaustion.
      OBJECTIVES: To determine the relationship between critical care nurses'
      perceptions of futile care and its effect on burnout. METHODS: A descriptive
      survey design was used with 60 critical care nurses who worked full-time and had
      a minimum of 1 year of critical care experience at the 2 participating hospitals
      (350-470 beds). Subjects completed a survey on demographics, the Moral Distress
      Scale, and the Maslach Burnout Inventory. Six research questions were tested. The
      results of the following question are presented: Is there a relationship between
      frequency of moral distress situations involving futile care and emotional
      exhaustion? RESULTS: A Pearson product moment correlational analysis indicated a
      significant positive correlation between the score on the emotional exhaustion
      subscale of the Maslach Burnout Inventory and the score on the frequency subscale
      of the Moral Distress Scale. Moral distress accounted for 10% of the variance in
      emotional exhaustion. Demographic variables of age, education, religion, and
      rotation between the critical care units were significantly related to the major
      variables. CONCLUSIONS: In critical care nurses, the frequency of moral distress
      situations that are perceived as futile or nonbeneficial to their patients has a
      significant relationship to the experience of emotional exhaustion, a main
      component of burnout.

PMID- 15149055
TI  - Communication ability, method, and content among nonspeaking nonsurviving
      patients treated with mechanical ventilation in the intensive care unit.
AB  - OBJECTIVE: To describe the communication ability, methods, and content among
      nonspeaking nonsurviving patients treated with mechanical ventilation in an
      intensive care unit. METHODS: Fifty patients who received mechanical ventilation
      and died during hospitalization were randomly selected from all adult patients (N
      = 396) treated in 8 ICUs in a tertiary medical center during a 12-month period.
      Clinicians' notes, use of physical restraints, and medication records were
      reviewed retrospectively. Data on communication method, use of sedation/analgesia
      (within 4 hours of communication event), and use of physical restraints were
      recorded on an investigator-developed communication event record for the first 10
      communication episodes documented in each patient's record (n = 275). Message
      content and method were recorded for every documented communication episode (n =
      694), resulting in a total of 812 content and 771 method data codes. RESULTS:
      Most charts (72%) had documentation of communication by patients at some time
      during mechanical ventilation. Most documented communication exchanges were
      between patients and nurses. Primary methods of communication were head nods,
      mouthing words, gesture, and writing. Physical restraints were used in half of
      the patients. However, most of the documented communication episodes (127/202,
      62.9%) occurred when physical restraints were not in use. Communication content
      was primarily related to pain, symptoms, feelings, and physical needs. Patients
      also initiated communication about their homes, families, and conditions.
      CONCLUSIONS: A clinically significant proportion of nonsurviving patients treated
      with mechanical ventilation in the intensive care unit communicate to nurses,
      other clinicians, andfamily members primarily through gesture, head nods, and
      mouthing words.

PMID- 15149056
TI  - Outcomes associated with enteral tube feedings in a medical intensive care unit.
AB  - BACKGROUND Underfeeding of patients reliant on enteral tube feedings most likely
      is due primarily to interruptions in the infusions. Strategies to improve energy
      intake require an understanding of such interruptions and associated outcomes.
      OBJECTIVES: To compare daily energy intake with goal energy intake; to ascertain
      frequency, duration, and reasons for interruptions in feedings, and to determine
      occurrences of feeding intolerance. METHODS: A prospective, descriptive study of
      a convenience sample of patients admitted during a 3-month period to a medical
      intensive care unit. Patients were included who were expected to receive
      continuous enteral tube feedings for at least 48 hours. Patients were studied
      until discontinuation of feedings, discharge from the unit, or death. RESULTS:
      Thirty-nine patients were studied for 276 feeding days. Patients received a mean
      of 64% of goal energy intake. Mean length of interruptions in feeding was 5.23
      hours per patient per day. Interruptions for performance of tests and procedures
      accounted for 35.7% of the total cessation in feeding time. Next most time
      consuming interruptions occurred with changes in body position (15%), unstable
      clinical conditions (13.5%), high gastric residual volume (11.5%), and nausea and
      vomiting (9.2%). Patients had diarrhea 105 (38%) of 276 feeding days. Gastric
      residual volumes exceeded 150 mL on 28 measurements in 11 patients. Five patients
      experienced episodes of nausea and vomiting. Four patients experienced an episode
      of feeding aspiration. CONCLUSIONS Precautionary interruptions in enteral
      feedings to decrease presumed risk of aspiration occurred frequently and resulted
      in underfeeding. Episodes of vomiting and of aspiration were uncommon.

PMID- 15149057
TI  - Comparison of signal quality between EASI and Mason-Likar 12-lead
      electrocardiograms during physical activity.
AB  - BACKGROUND: Myoelectric noise and baseline wander, artifacts that appear when
      patients move during electrocardiographic monitoring, can cause false alarms.
      This problem can be addressed by using a reduced lead set and placing electrodes
      on the anterior part of the torso only. The Mason-Likar modification of the
      standard 12-lead electrocardiogram and the EASI lead system are 2 alternative
      systems for lead placement. OBJECTIVES: To test the hypothesis that the EASI lead
      system is less susceptible to artifacts than is the Mason-Likar modification of
      the standard 12-lead electrocardiogram. METHODS: Baseline wander and myoelectric
      noise amplitudes of EASI and Mason-Likar 12-lead electrocardiograms were
      compared. Twenty healthy volunteers participated. Both lead systems were recorded
      simultaneously for different types of physical activities. For each lead in each
      subject, baseline wander and myoelectric noise were measured for both systems, at
      rest and during each physical activity. RESULTS: The outcome for baseline wander
      was mixed. For myoelectric noise content, the EASI system performed better for
      the limb leads in the different physical activities. In the precordial leads, the
      differences were minimal or mixed. However, for supine-to-right turning, EASI
      performed worse than the Mason-Likar system. CONCLUSIONS: The 2 systems have
      similar susceptibilities to baseline wander. The EASI system is, however, less
      susceptible to myoelectric noise than is the Mason-Likar system. EASI performed
      worse than Mason-Likar for turning supine to right, because only the EASI system
      uses an electrode in the right-midaxillary line.

PMID- 15149058
TI  - Comparison of traditional and disposable bed baths in critically ill patients.
AB  - BACKGROUND: For bedridden patients unable to perform personal hygiene measures
      because of acute illness or chronic debilitation, the bed bath, with either the
      traditional basin or, more recently, disposable baths, has long been a measure
      for improving hygiene and costs. OBJECTIVE: To compare the traditional basin bed
      bath with a prepackaged disposable bed bath in terms of 4 outcomes: time and
      quality of bath, microbial counts on the skin, nurses' satisfaction, and costs.
      METHODS: Forty patients in surgical, medical, or cardiothoracic intensive care
      units received both types of bath on different days. Baths were observed, timed,
      and scored for quality. Cultures of the peri-umbilicus and groin were obtained
      before and after each bath. At the end of the study, nurses were interviewed
      about their preferences. RESULTS: Neither total quality scores nor microbial
      counts differed significantly between the 2 bath types. Significantly fewer
      products (P < .001) and less time were used, cost was lower, and nurses' ratings
      were significantly better with the disposable bath. CONCLUSION: The disposable
      bath is a desirable form of bathing for patients who are unable to bathe
      themselves in critical care and long-term care settings, and it may even be
      preferable to the traditional basin bath.

PMID- 15149059
TI  - Visionary leaders as moral sources: a tribute to Dr Gloria Smith.

PMID- 15149060
TI  - Statin pleiotropy: fact or fiction?
AB  - Accumulating evidence from clinical trials and basic research indicates that
      statin therapy favorably influences a number of diverse clinical events through
      both effects related to lowering of LDL cholesterol levels and effects
      independent of the lowering of LDL cholesterol levels. The latter effects are
      referred to as pleiotropic. The full potential of this exciting class of drugs in
      vascular and nonvascular protection is only just being realized. The pleiotropic
      effects of the statins improve vascular relaxation, promote new vessel formation,
      and stabilize unstable plaques. Statins reduce glomerular injury, renal disease
      progression, insulin resistance, and bone resorption. Ezetimibe, a recently
      approved medication, enhances the lipid-lowering effects of the statins by
      lowering LDL and increasing HDL levels through its property of inhibiting
      absorption of cholesterol in the small intestine. These salutary effects of
      ezetimibe on statin levels presumably enhance the beneficial effects attributed
      to statin pleiotropy. It is noteworthy that the pleiotropic properties of the
      statins have been beneficial in a variety of diseases that involve a number of
      organs and organ systems. No other therapeutic agent can claim equally stellar
      results in such a wide variety of diseases. The common denominator in all of the
      diseases that have been shown to improve with statin pleiotropy could be
      arteriolar pathology due to hyperlipidemia, which improves in response to statins
      by a return of arteriolar function to normal rather than through statin
      pleiotropy. Recent reports indicate that higher doses of statins reverse
      atheromatous changes in the coronary artery when the LDL cholesterol level is
      lowered to well below 2.59 mmol/L (100 mg/dL). These results lend additional
      support to the probability that similar pathological changes that may be present
      in the small arteries and arterioles also can respond to adequate statin therapy.
      Statin pleiotropy: fact or fiction?

PMID- 15149062
TI  - Australia's live animal exports set to improve.

PMID- 15149063
TI  - University of Melbourne awards Roger Clarke DVSc (honoris causa).

PMID- 15149061
TI  - Retrograde atrial conduction.

PMID- 15149064
TI  - Slaughtering the sacred cows.

PMID- 15149065
TI  - Letter from Europe.

PMID- 15149066
TI  - Sex discrimination--could you be guilty?

PMID- 15149067
TI  - Ban could fleece industry.

PMID- 15149068
TI  - Achieving a balance.

PMID- 15149069
TI  - Use of free conjunctival grafts in horses: ten cases.
AB  - OBJECTIVE: To assess the effectiveness of free conjunctival grafts in the
      treatment of horses with a range of keratopathies. DESIGN: A retrospective
      clinical study of ten client-owned horses treated at Murdoch University
      Veterinary Hospital from May 1996 to September 2001. PROCEDURE: The suitability
      of patients for the surgical procedure was assessed using a slit lamp
      biomicroscope and by direct and indirect ophthalmoscopy. Surgery was performed
      with the aid of an operating microscope, under general anaesthesia. A
      subpalpebral ocular lavage catheter was used for administration of topical
      atropine and antibiotics postoperatively. RESULTS: In all ten horses the affected
      globe was saved. In nine of the horses vision in the eye was satisfactory 6
      months after surgery, and in one horse the eye was blind. Complications included
      further corneal ulceration or eyelid abscessation and some loss of sutures,
      although these did not preclude a successful outcome. CONCLUSION: Free
      conjunctival grafts were successful in treating a range of keratopathies in the
      horse, and the technique offers a number of advantages over other forms of
      surgical intervention.

PMID- 15149070
TI  - Retrospective study of Old World screwworm fly (Chrysomya bezziana) myiasis in 59
      dogs in Hong Kong over a one year period.
AB  - This retrospective study examined the case records of Old World screw-worm fly
      myiasis in dogs in Hong Kong's New Territories. Myiasis due to OWSWF was
      identified and treated in 59 dogs at our clinic over a period of 1 year.
      Signalment, causes of initial wound, and treatments implemented, are reported.
      All cases recovered from myiasis with a combination of larvae removal and wound
      debridement, antibiotics, and topical and systemic insecticides. Whilst this
      parasite is currently exotic to Australia, much of the country is environmentally
      suitable (tropical and subtropical) for establishment of OWSWF.

PMID- 15149071
TI  - Haemangiosarcoma of the urinary bladder in a dog.
AB  - Haemangiosarcoma of the urinary bladder is reported in a dog. The bladder mass
      was detected incidentally during physical examination. Partial cystectomy with
      unilateral ureteroneocystostomy were performed to remove the tumour en bloc.
      Necrosis of the urinary bladder was diagnosed 10 days postoperatively and the dog
      was euthanased.

PMID- 15149072
TI  - Eradication of the camelid biting louse, Bovicola breviceps.

PMID- 15149073
TI  - Specificity of an immunochromatographic test for anthrax.
AB  - OBJECTIVE: To evaluate the specificity of an immunochromatographic test (ICT) for
      anthrax in cattle. DESIGN: A comparison of an ICT with blood smear and culture in
      uninfected cattle. PROCEDURE: Two hundred and forty blood samples were collected
      from dead cattle at two knackeries within Victoria and tested on-site with an ICT
      for the detection of protective antigen (PA) of Bacillus anthracis. Blood smears
      were prepared on-site and blood samples transported to the laboratory for aerobic
      and anaerobic culture. The results of the ICT were compared with blood smear and
      culture. Animals were regarded as not infected with B anthracis if the organism
      was not detected in a stained blood smear or on culture. Ten healthy yearling
      cattle were vaccinated with live spore anthrax vaccine and blood samples
      collected on days 0 to 7 and day 15 were tested in the ICT for the presence of
      PA. RESULTS: All blood samples from the 240 knackery cattle were ICT, smear and
      culture negative. All blood samples from the 10 vaccinated cattle were ICT
      negative. CONCLUSION: The ICT is a test with high specificity in cattle (98.5 to
      100%; 95% CI) and recent vaccination of cattle does not give rise to positive
      reactions.

PMID- 15149075
TI  - Effect of a test and control program for bovine Johne's disease in Victorian
      dairy herds 1992 - 2002.
AB  - OBJECTIVE: To report on progress in Johne's disease (JD) control in infected
      dairy herds participating in the Victorian Johne's disease Test and Control
      Program (TCP). PROCEDURE: Clinical histories and JD testing data recorded by the
      Department of Natural Resources and Environment (now called Department of Primary
      Industries) were analysed for 542 dairy herds participating in the TCP. The herds
      were required to conduct annual herd tests of cattle 2 years old and older with
      an enzyme linked immunosorbent assay (ELISA), cull the reactors and manage the
      younger cattle to minimise infection. RESULTS: Testing of over 680,000 animals
      identified over 10,000 reactors giving an average prevalence of reactors at the
      first whole-herd test (T1) of 1.78%. There was a relatively rapid increase in the
      incidence of clinical disease before the TCP started and then it markedly
      declined. There was a slow and interrupted decline in reactor prevalence, with a
      marked peak occurring at the fourth herd test (T4). The average age of reactors
      and clinical cases was 5.7 and 5.9 years, respectively. Of the reactors and
      clinical cases detected during the TCP, 87% and 95% respectively, were born
      before the TCP started. Thirty herds completed the program by achieving three
      successive negative whole herd tests and 91 herds dropped out because of
      inability to comply with the agreed requirements of the program. There were no
      home-bred reactors born after the start of the program in 253 (47%) herds and of
      the 522 herds that were tested more than once, there were 319 (61%) herds in
      which no home-bred reactors were detected after the first year of testing. The
      number of ELISA positive animals detected at T1 appeared to be only about 26% of
      the animals from that round that subsequently became positive or developed
      clinical disease at later test rounds. CONCLUSION: The TCP caused a marked
      decline in the number of clinical cases, probably because animals in which
      clinical disease was imminent were detected by testing and removed. A reduction
      in prevalence of reactors occurred only when most herd members were born after
      the TCP started. The sensitivity of the ELISA appears to be low based on the
      large number of reactors that were negative at T1 but were positive at later
      tests. Low sensitivity of diagnostic tests and the long incubation period of the
      disease limits meaningful analysis of the program until it has continued for some
      years. Measures adopted in the TCP have not broken the cycle of infection in many
      participating herds. It is unsure if this was because of poor compliance with
      control recommendations or a poor understanding of methods of transmission by
      scientists. Eradication is not feasible in the short-term.

PMID- 15149074
TI  - Survey for papillomatous digital dermatitis in Australian dairy cattle.
AB  - OBJECTIVE: To determine whether Treponema-associated papillomatous digital
      dermatitis (PDD) occurs in Australian dairy cattle. DESIGN: Mail-out
      questionnaire and histological and bacteriological examination of biopsy tissue
      from suspect PDD lesions. PROCEDURE: The questionnaire was mailed to 375
      veterinarians to evaluate their knowledge of PDD, determine if they had observed
      the disease in Australian dairy cattle, and to request biopsy material from
      suspicious cases. Biopsies were examined for histological and bacteriological
      evidence of PDD, including for the presence of spirochaetes. RESULTS: Eighty
      eight replies to the questionnaire were received (23.5%). Of 52 respondents who
      were aware of PDD as a possible cause of lameness, 26 reported observing the
      condition in Australian cattle. Of 32 respondents who were unaware of the
      condition, 6 reported observing lesions that might have been PDD. The majority of
      reports of PDD-like lesions came from the southern Australian states, the
      condition occurring during periods of high rainfall and proving responsive to
      topical or parenteral application of antimicrobials. Biopsies from five erosive
      lesions showed histological similarity to PDD whereas biopsies from five
      proliferative lesions were consistent with chronic inflammation, fibroma or
      cutaneous papilloma. The presence of spirochaetes was not demonstrated in any of
      the lesions by histological or bacteriological methods. CONCLUSION: Anecdotal
      reports and analysis of biopsy material confirm that a condition similar to PDD
      does occur sporadically in dairy cattle in southern Australia. However, this
      condition has so far not been shown to be associated with the presence of
      spirochaetes in the lesions.

PMID- 15149076
TI  - Infection rates in reactors to an absorbed ELISA used in a test and cull program
      for bovine Johne's disease.
AB  - OBJECTIVE: To determine the proportion of cattle, whose sera gave positive
      reactions in a commercial enzyme linked immunosorbent assay (ELISA) for bovine
      Johne's disease, that were confirmed infected with Mycobacterium avium subsp
      paratuberculosis by histology and culture of tissues. PROCEDURE: Dairy cattle (n
      = 493) from the Echuca district of Victoria, whose sera were positive in the
      ELISA, were slaughtered at an abattoir where standard specimens were collected
      for histology and culture. Only if samples were histologically negative were
      further samples submitted for culture. RESULTS: The proportion of cattle in which
      infection was confirmed increased from 70.4% in 1996 to 89.4% in 2001 giving an
      overall confirmation rate of 79.9%. This was mainly because more reactors were
      confirmed by culture each year, the proportion increasing from 0% in 1997 to
      27.5% in 2000 but decreasing to 16.7% in 2001. If all unconfirmed reactors were
      presumed to be uninfected, the minimum specificity of the ELISA was 99.62%. There
      were no significant differences between the age groups in the proportion
      confirmed infected. CONCLUSION: Confirmation rates and specificity of the ELISA
      were high when used in a typical JD-infected Victorian dairy cattle population.
      Imperfect sensitivity of histology and culture and the selection of reactors
      which favoured more false positives, means the estimates were probably
      conservative. Confirmation rates were not affected by age of ELISA reactor.

PMID- 15149078
TI  - Developments on animal welfare in Egypt.

PMID- 15149077
TI  - Survey for the presence of White Spot Syndrome virus in Australian crustaceans.
AB  - Agriculture, Fisheries and Forestry - Australia, GPO Box 858, Canberra,
      Australian Capital Territory 2611.

PMID- 15149079
TI  - A health economic model to assess the long term effects and cost-effectiveness of
      PEG IFN alpha-2a in hepatitis C virus infected patients.
AB  - OBJECTIVES: Chronic Hepatitis C (CHC) is associated with long-term complications.
      Treating CHC with Pegylated interferon alpha-2a (PEG IFN alpha-2a) improves
      response rates and may contribute to less morbidity and mortality compared to
      standard interferon therapy. The objectives of this study were to estimate the
      long-term clinical consequences of such treatment as well as the resulting cost
      effectiveness. RESEARCH DESIGN AND METHODS: A Markov model was developed in order
      to predict the clinical and economic outcomes over a 25 year period. Three
      analyses were conducted: 1. for all Hepatitis C Virus (HCV) genotypes where PEG
      IFN alpha-2a was compared to interferon alpha-2a (IFN alpha-2a) in monotherapy
      for 48 weeks; 2. for the HCV genotypes 1-4-5-6 comparing PEG IFN alpha-2a with
      interferon alpha-2b (IFN alpha-2b) both combined with ribavirin 1000/1200 mg for
      48 weeks; and 3, where PEG IFN alpha-2a with 800 mg ribavirin was compared to IFN
      alpha-2b with ribavirin 1000/1200 mg for 24 weeks in genotypes 2 and 3. RESULTS:
      In analysis one the cost-effectiveness of PEG IFN alpha-2a is 4,569/quality
      adjusted life year (QALY) gained. In the second analysis, the result was 14,763
      euros/QALY, while for the 24 weeks therapy (analysis 3) the result was 903 per
      QALY gained. In an extensive sensitivity analysis cost-effectiveness was
      confirmed within reasonable assumptions. CONCLUSIONS: These results suggest that
      PEG IFN alpha-2a is cost-effective in the management of all CHC patients. Real
      life evidence about longer term benefits of PEG IFN alpha-2a will be of
      importance for future decision making.

PMID- 15149080
TI  - The management of rectal cancer in Belgium: a survey of our practice.

PMID- 15149081
TI  - BASL guidelines for the surveillance, diagnosis and treatment of hepatocellular
      carcinoma.

PMID- 15149082
TI  - Gastrointestinal cancer.

PMID- 15149084
TI  - Critical review in the surgical pathology of carcinoma of the stomach.
AB  - Further to a thorough analysis of the management of the surgical specimen for
      gastric carcinomas, guidelines were defined following several recommendations
      including informative gross and microscopic descriptions associated to a final
      correct staging of the tumour, according to the TNM classification and must at
      least include tumour penetration, nodal or distant metastases. The Belgian
      working party for GI cancer debate on these data and present a check-list that
      would help pathologists.

PMID- 15149083
TI  - Histopathological reporting of resected carcinomas of the oesophagus and gastro
      oesophageal junction.

PMID- 15149085
TI  - Recommendations for pathological examination and reporting for colorectal cancer.
      Belgian consensus.

PMID- 15149086
TI  - Guidelines for adequate histopathological reporting of pancreatic ductal
      adenocarcinoma resection specimens.

PMID- 15149087
TI  - Prophylaxis of first variceal bleeding.

PMID- 15149088
TI  - Entomopathogenic nematodes in the European biocontrol market.
AB  - In Europe total revenues in the biocontrol market have reached approximately 200
      million Euros. The sector with the highest turn-over is the market for beneficial
      invertebrates with a 55% share, followed by microbial agents with approximately
      25%. Annual growth rates of up to 20% have been estimated. Besides microbial
      plant protection products that are currently in the process of re-registration,
      several microbial products have been registered or are in the process of
      registration, following the EU directive 91/414. Entomopathogenic nematodes (EPN)
      are exceptionally safe biocontrol agents. Until today, they are exempted from
      registration in most European countries, the reason why SMEs were able to offer
      economically reasonable nematode-based products. The development of technology
      for mass production in liquid media significantly reduced the product costs and
      accelerated the introduction of nematode products in tree nurseries, ornamentals,
      strawberries, mushrooms, citrus and turf. Progress in storage and formulation
      technology has resulted in high quality products which are more resistant to
      environmental extremes occurring during transportation to the user. The
      cooperation between science, industry and extension within the EU COST Action 819
      has supported the development of quality control methods. Today four companies
      produce EPN in liquid culture, offering 8 different nematode species. Problems
      with soil insects are increasing. Grubs, like Melolontha melolontha and other
      scarabaeidae cause damage in orchards and turf. Since the introduction of the
      Western Corn Rootworm Diabrotica virgifera into Serbia in 1992, this pests as
      spread all over the Balkan Region and has reached Italy, France and Austria.
      These soil insect pests are potential targets for EPN. The development of
      insecticide resistance has opened another sector for EPN. Novel adjuvants used to
      improve formulation of EPN have enabled the foliar application against Western
      Flower Thrips and Plutella xylostella. To reach these markets, the product costs
      for EPN will have to further decrease in the future. One possibility to reduce
      application costs related with the use of EPN is the inoculative application to
      cause long term effects on pest populations.

PMID- 15149089
TI  - Biocontrol of foliar pathogens: mechanisms and application.
AB  - Biocontrol offers attractive alternatives or supplements to the use of
      conventional methods for plant disease management. Vast experience has been
      gained in the biocontrol of plant diseases. Prevention of infection by biocontrol
      agents or suppression of disease is based on various modes of action. Pathogens
      are typically affected by certain modes of actions and not by others according to
      their nature (i.e. biotrophs vs. necrotrophs). Resistance in the host plant may
      be induced locally or systemically by either live or dead cells of the biocontrol
      agent and may affect pathogens of various groups. As some pathogens are
      negatively affected by lake of nutrients in the infection court, competition for
      nutrients and space was long recognized as antagonism trait. Antibiosis and
      hyperparasitism affect pathogens of various groups. Other valid mechanisms are
      reduction of the saprophytic ability and reducing spore dissemination. Recently
      it was revealed that restraining of pathogenicity factors of the pathogens, i.e.
      host hydrolyzing proteins or reactive oxygen species takes place when biocontrol
      is used. It is likely that several modes of action concomitantly participate in
      pathogens suppression but the relative importance of each one of them is not
      clear. Examples of effective prevention of infection in the phyllosphere that
      rely on multiple modes of action will be demonstrated with Trichodermo harzianum
      T39 (TRICHODEX), Bacillus mycoides and Pichia guilermondii, a filamentous fungus,
      bacterium and yeast biocontrol agents, respectively. Several commercial products
      based on microorganisms have been developed and are starting to penetrate the
      market. However, large-scale use is still limited because of variability and
      inconsistency of biocontrol activity. In some cases this may be caused by
      sensitivity of the biocontrol agents to environmental influences. Ways to
      overcome biocontrol limitations and to improve its efficacy are i. integration of
      biocontrol with chemical fungicides on a calendar basis or according to
      ecological requirements of the biocontrol agents relying on the advise of a
      decision support system; ii. introduction of two or more biocontrol agents in a
      mixture, assuming that each one of them has different ecological requirements
      and/or different modes of action. Implementation of one (or more) of these
      approaches, using biocontrol preparations mentioned above lowered the variability
      and increased the consistency of disease suppression. The expected long-term
      result of the implementation of these suggested strategies is reduced risk of
      uncontrolled epidemics and increase of confidence of growers in using this non
      chemical control measure on a large scale.

PMID- 15149090
TI  - Homage to Robert Lee Metcalf (1916-1998): entomologist, environmental
      toxicologist, and insect chemical ecologist.
AB  - The late Professor R.L. Metcalf is being honored as one of the leading
      entomologists of the 20th century, whose worldwide influence on entomology,
      insecticide and environmental toxicology, and insect chemical ecology was
      enormous. His 82-year life span mirrored the transition in entomology from the
      early descriptive phase of insect and plant and animal interactions to the more
      detailed integration of the biochemical, physiological, behavioral, ecological,
      and environmental understanding of nature within the context of societal issues
      and needs. New techniques, some relatively simple but never-the-less ingenious,
      paved his way to fame. Metcalf was an enormously productive scientist. His 450+
      research publications, numerous books and editorships, patents, internationally
      oriented staff of students, postdocs and associates, and his contributions to
      teaching and to public service let him stand out as a challenging role model for
      those young minds starting their careers at the beginning of the 21st century.

PMID- 15149091
TI  - Introduction of Diabrotica virgifera virgifera into the Old World and its
      consequences: a recently acquired invasive alien pest species on Zea mays from
      North America.
AB  - Diabrotica v. virgifera LeConte (Coleoptera: Chrysomelidae), (in short D.v.v.),
      with common name western corn rootworm, is endemic to the New World. Originating
      in the regions from South America to Mexico where it was in biological
      equilibrium with its natural enemies, predators and pathogens, it moved north
      with its food plants. Probably due to human agricultural farm practices with
      preference for monoculture of maize, the insect found open niches for expanding
      to the midwestern US where LeConte first described the species in Nebraska in
      1867. Cyclodiene insecticide resistance, discovered in 1961, accelerated its
      spread and movement across the Great Plaines to the Atlantic Coast where it
      arrived around 1980. D.v.v. is a costly adversary to maize, to cucurbit, and,
      because of recent hostshifts, a threat to soybean production. Booming air travel
      and shipments of goods by air provided opportunities for D.v.v., without its
      natural enemies, to invade Europe where the insect was first described by F. Baca
      in 1993 near Belgrade airport (Baca 1993, Camprag & Baca 1995). From this focal
      point, D.v.v. expanded its range in all directions. Ten years later, in 2002,
      most of southeastern Europe has D.v.v. populations, some of them reaching
      economic damage levels such as those in Serbia, Croatia, and Hungary. New spot
      infestations in Northern Italy (Veneto, Lombardy, Piemonte) and in the Ticino
      region of Southern Switzerland, but also in Austria, Slovakia, Czechia, the
      Ukraine, even France, signal the final arrival of D.v.v. in Central Europe. The
      Alps, formerlyconsidered a natural barrier, might be circumvented or trespassed
      via air and road traffic. Model calculations by Baufeld and Enzian (2003) show
      that climatic and survival conditions are favorable for D.v.v. in all of Central
      Europe. Yet, in spite of well known annual losses of one billion dollars in the
      US, an effective and sustainable European strategy for keeping D.v.v. in check is
      still missing.

PMID- 15149092
TI  - Effects of different growing systems and fertiliser rates on attractiveness of
      maize crop to beetles of Diabrotica virgifera virgifera LeConte and larvae
      dammage.
AB  - Monitoring of plant lodging, yield reaction due to root injures caused by western
      corn rootworm larvae (WCR) (Diabroticia virgifera virgifera Le Conte) and adults
      abundance with yellow Multigard and Pherocone AM and pheromone Csalomon traps,
      were performed in three field trials. First one with 4 variants of maize growing
      system; maize continuous cropping, two crop rotation (wheat-maize, soybean-maize)
      and three crop rotation (wheat-soybean-maize), set up in 1985. Second one with 54
      variants, both conducted in Zemun Polje. A large scale trial with three rates of
      NPK mineral fertilizers; (NPK 0 kg/ha, 170 kg/ha and 270 kg/ha with two type of N
      applied in side dressing (N 0 kg/ha, 50 kg/ha and 80 kg/ha) was set up in Crepaja
      in 1997, 1998 and 1999. Each variant of fertilizers had two combinations; one
      treated with insecticide and another one untreated check. Feeding on root system
      of WCR larvae, in the variants with insecticide application, resulted in plant
      lodging that ranged in average from 2.1% in 1997, to 61.6% in 1999, while in
      variant without insecticide application, root damage resulted in plant lodging
      from 19.5% in 1997, to 56.6% in 1999. Increasing of the nitrogen rates in the
      variants without application of insecticide tended to raise the percentage of
      plant lodging Yield reaction on nitrogen application was positive in 1997, first
      year and 1998, second year of maize monoculture, while in 1999 was negative.
      Larval injury affected maize yield in the higher extend in extremely dry year
      2000, when yield index was 0.37 comparing 2.86 t/ha in maize monoculture to 7.66
      t/ha in three crop rotation, 0.54 (2.86: 5.28 maize monoculture: wheat-maize) and
      0.55 (2.86: 5.22 maize monoculture: soybean-maize). Adult abundance monitored
      with yellow sticky and pheromone traps indicate that maize in three crop rotation
      has the smallest attraction to the migratory WCR beetles. The choice of three
      crop rotation seems to be the most promising choice for maize growing, which will
      result with the lowest risk of plant lodging and yield decrease.

PMID- 15149093
TI  - A monitoring trap for Diabrotica virgifera virgifera and D. barberi adults lured
      with a poisoned cucurbitacin bait.
AB  - A trap is described that uses as a simple natural ingredient a cucurbitacin
      mixture to capture and carbaryl insecticide to kill northern and western corn
      rootworm beetles (Diabrotica barberi Smith and Lawrence, and Diabrotica virgifera
      virgifera LeConte (D.v.v.), respectively). The trap is consistent in numbers of
      beetles captured per trap per day, and it should be useful in integrated pest
      management programs to monitor the population density of rootworm beetles in corn
      fields. Captures between 1981 and 1983 in Illinois showed that western corn
      rootworm adults that disperse into first-year cornfields were predominantly
      females. These traps are being utilized today (2003) by many researchers in the
      New World desiring to know more about rootworm beetle movement and activities.
      Entomologists in the Old World confronted with the alien invasive pest D.v.v.
      should profit likewise from increased knowledge and availability of these traps
      for Diabrotica management.

PMID- 15149094
TI  - Diabrotica egg separation from soil: an efficient and fast procedure for
      monitoring egg stages of corn rootworm populations.
AB  - Maize growers repeatedly are confronted with the need to make predictions and
      decisions about which of their fields are likely to develop corn rootworm
      populations above the economic threshold and are in need of treatment. One of the
      best parameters that can help as a basis for these decisions are corn rootworm
      egg counts in the soil. The Western corn rootworms have one generation each year.
      Females oviposit eggs in the soil in corn fields from late July through early
      September. These eggs overwinter in the soil and almost all hatch the following
      June. An apparatus is described that utilizes water, MgSO4 solution and differing
      screen sieves for extracting the rootworm eggs from the soil samples collected
      from the field after deciding on an acceptable sampling procedure. Samples may be
      a composite of subsamples or a number of individual samples taken at various
      locations in a field. The Illinois machine and the final separation of eggs,
      using flotation in 2 molar MgSO4 solution, are highly efficient, and recoveries
      of 97% of rootworm eggs manually placed in samples of soil have repeatedly been
      achieved. Thus, this would be a useful tool in integrated pest management
      programs that monitor the density of corn rootworm eggs in corn fields.

PMID- 15149095
TI  - Time of planting and choice of maize hybrids in controlling WCR (Diabrotica
      virgifera virgifera Le Conte) in Serbia and Montenegro.
AB  - Effects of the length of growing season of maize hybrids (FAO maturity groups
      400, 500, 600 and 700) and planting dates on the maize crop, as an attractive
      supplemental feeding for western corn rootworm (WCR) beetles and larval survival,
      were observed in two locations of South Banat, during a three-year (1997-1999)
      and a two-year period (2001 and 2002). The feeding attraction of the maize crop
      for WCR beetles and survival of larvae were evaluated in dependency of the
      variable "plant lodging". The following results were obtained: First location: A.
      Plant lodging over time of planting and applied insecticides. 1. Early planting:
      44.2%, 77.6%, and 76.7% for FAO 400, 500 and 600, respectively. 2. Late planting:
      4.7%, 14.9%, and 7.9% for FAO 400, 500 and 600, respectively. B. Plant lodging
      over time of planting and cropping practices: 1. Early planting without
      insecticide application 72.2%, and with insecticide application 7.3%. The
      efficacy of application of insecticide carbofurane (Furadan 350 FS, dosage 4.0
      liter/ha) in larval control was 89.9%. 2. Late planting without insecticide
      application, plant lodging was 47.7%, and with insecticide application 8.1%. The
      efficacy of application of insecticide carbofurane (Furadan 350 FS, dosage 4.0
      l/ha-1) in larval control was 83.0%. Early planting resulted in greater survival
      of larvae; hence plant lodging was 10 times greater in early than in late
      planting. The percentage of lodged plants indicates that the maize crop in late
      planting was more attractive to imagoes. Therefore, more lodged plants were
      observed in the treatment where late planting preceded. Second location: Plant
      lodging as dependent on "treatments" 1. Regular plantings: 90.7% in untreated
      control and 76.2% in insecticide treated variant. The efficacy of insecticide
      application in control of high larval population was 16.0%. 2. Replanting date:
      12.2% in untreated and 4.4% in treated variant. The efficacy of insecticide in
      control of low larval population increased from 16.0 to 63.9%. To successfully
      decrease the size and intensity of attacks of the Diabrotica v. virgifera
      population under conditions of applying insecticides or not, it is necessary to
      use maize hybrids of the earliest possible maturity group and to plant the seed
      on the earliest date possible in the first year of growing maize, if maize is to
      be followed by maize in the next year.

PMID- 15149096
TI  - Distribution patterns of MCA-coated granules aerially applied to corn fields of
      Southern Hungary between 2000 and 2002.
AB  - Field studies in corn (Zea mays L.) were conducted to evaluate distribution
      patterns of 4-methoxy-cinnamaldehyde (MCA) coated corn grits after aerial
      application with a Dromader fixed wing aircraft. The kairomone mimic MCA is
      synthetically available and a quite specific and efficient adult attractant for
      the invasive alien maize pest western corn rootworm (WCR) Diabrotica virgifera
      virgifera LeConte. Orientation disruptive properties of MCA for WCR when applied
      at unphysiologically high concentrations are currently under investigation. For
      successful implementation of the MCA disruption technique, the distribution
      patterns of MCA coated corn granules ('grits') in the field are important. Grits
      are degrained corn cobs, shredded to different sizes, coated with MCA and used as
      a carrier material to disseminate MCA vapors into corn fields. Granules of 10-12
      mesh size were aerially applied eight times at rates ranging from 12.4 to 25.0
      kg/ha. The goal is to evaluate distribution patterns of corn grits treated with
      MCA in three fields located at Csanadpalota, Kardoskut and Mezohegyes in Southern
      Hungary between 2000 and 2002. Increasing rates reflect our attempts in finding
      and optimising the most even distribution of granules in the field. Field
      experiments were evaluated by collecting grits in 30-cm plastic saucers and by
      counting grits accumulated on corn plant parts. Variation in grit number per unit
      area and frequency of corn granule number per plant showed some transient
      technical application problems. Analysis of grits collected in the saucers
      revealed some statistical difference between the different application dates as
      well as differences in rates applied. Altogether grits in saucers were more
      evenly distributed in comparison to the grits collected on plant parts. As the
      corn plants age, their leaves and whorls present a smaller and smaller surface
      area where granules can accumulate. Altogether, however, grit distribution
      patterns indicate that aerial application is a viable tool for disseminating MCA
      in corn fields.

PMID- 15149097
TI  - Orientation disruption of Diabrotica virgifera virgifera in maize by a liquid MCA
      formulation released from paper squares in the Banat region of Serbia and
      Montenegro.
AB  - Serbia-Montenegro, formerly the Republic of Yugoslavia, is the first European
      Country where Diabrotica virgifera virgifera Le Conte (Col.: Chrysomelidae)
      (D.v.v.) was reported in 1992 as an invasive alien pest species, Baca (1993),
      Camprag and Baca, (1995): From a focal point near Belgrade airport, the maize
      pest quickly spread in all directions reaching the economic threshold in a number
      of surrounding countries around 1995. The field experiments described took place
      in the Banat region east of Belgrade in July of 2002. The plant kairomone mimic 4
      methoxycinnamaldehyde (MCA) dissolved in acetone was slowly volatilized from
      paper squares. It permeated a maize field of known D.v.v. history of 0.5 ha size
      3 km north of the village of Crepaja. With release rates of 266 g/ha, max.
      orientation disruption levels of 55% were achieved. The total amount of MCA was
      distributed in two manual applications. Readings of orientation levels were
      continued for eleven days during the latter part of July and into early August of
      2002.

PMID- 15149098
TI  - Are nematode collections in danger of extinction?
AB  - The correct identification of pest organisms, including plant-parasitic
      nematodes, is the essential foundation for integrated pest programmes and
      government policy decisions involving trade. A plethora of identification methods
      have been developed but the basis for identification remains essentially
      morphological in nature, with invertebrate collections forming the ultimate
      reference facility. However, a continuing decline in funds for the preservation
      and curation of collections and for the development of taxonomists is leading to
      a deterioration in the quality of standards. The development of computer
      technology associated with digital images and their analysis provides the
      possibility of not only attracting resources but also of exposing collections to
      international use in ways not previously possible. The time is right to develop a
      European strategy to save and develop collections and taxonomy.

PMID- 15149099
TI  - Chemical alternatives for soil fumigation with methyl bromide on tobacco seedbeds
      in nematode and weed control.
AB  - The proposed phase out of methyl bromide necessitated the evaluation of a number
      of chemical alternatives to replace it. The recommended rate of application for
      methyl bromide, 50 g/m2 was evaluated over three years against various rates of
      65% 1,3-Dichloropropene mixed with 35% chloropicrin (1,3-D/C-35); a combination
      of metham sodium and ethylene dibromide (EDB) and 65% 1,3-Dichloropropene (1,3-D)
      alone. Chloropicrin and 1,3-D have long been registered and used in Zimbabwe as
      individual chemicals and their combination as a single product had never been
      tested. 1,3-D/C-35 at 36.9 ml/m2 was as effective as methyl bromide in nematode
      and weed control and led to similar seed germination and seedling growth rate. A
      combination of EDB at 21 ml/m2 and metham sodium at 35 ml/m2 was also equally
      effective. The use of 1,3-D alone at 35 ml/m2 gave unsatisfactory weed control
      and led to a reduced seedling growth rate. Metham sodium alone at 35 ml/m2 gave
      comparable weed control, seed germination and seedling growth comparable with
      methyl bromide. However nematode control evaluated using a gall rating scale was
      reduced. 1,3-D/C-35 at 36.9 ml/m2 and metham sodium at 35 ml/m2 used in
      combination with EDB at 21 ml/m2 are therefore, possible replacements for methyl
      bromide soil fumigation in tobacco seedbeds.

PMID- 15149100
TI  - Efficacy of Paecilomyces lilacinus (strain 251) for the control of root-knot
      nematodes.
AB  - The egg pathogenic fungus Paecilomyces lilacinus (strain 251), is a unique strain
      with a wide range of activity against the most important plant parasitic
      nematodes. Due to increased production capacity by solid state fermentation and a
      new water dispersible granule (WDG) formulation, this biological nematicide may
      be used in an integrated approach to control plant parasitic nematodes. Dose
      response experiments were conducted with the root-knot nematode Meloidogyne
      incognita on tomatoes using the new WDG formulation. The results revealed a clear
      correlation between rate applied and the degree of control concerning the
      reduction in damage to the root and multiplication of the nematode. Best control
      was achieved by applying the biological nematicide at rates of 2 to 4 times 10(9)
      conidia per plant as a soil treatment one week before planting. Monitoring the P.
      lilacinus population in the rhizosphere showed a decline after 2 to 3 month which
      can lead to insufficient control over a full growing season. Repeated application
      to maintain the antagonist population at a sufficient level could be used to
      secure long term control of root-knot nematodes.

PMID- 15149101
TI  - Managing the mycorrhizosphere--an approach to sustainable agriculture after the
      phaseout of methyl bromide?
AB  - Plant Health Promoting Rhizobacteria (PHPR) with known biocontrol activity toward
      the root knot nematode, Meloidogyne incognito, were tested for their ability to
      promote root colonization of arbuscular mycorrhizal fungi on tomato under
      greenhouse conditions. In addition, bacteria isolated from mycorrhizal spores
      were tested for their direct biological control activity on nematode early root
      penetration. The nematode antagonistic rhizobacteria Rhizobium etli G12
      significantly increased mycorrhizal establishment. In addition, two of nine
      bacteria isolated from the mycorrhizosphere were shown to significantly reduce M.
      incognita early root penetration. The experiments produced important data on the
      interaction between rhizobacteria and the symbiotic fungus that in some
      combinations work synergistically in controlling the root-knot nematode. The
      potential of using such multitrophic treatment combinations in integrated
      management targeted first at reducing nematode early root penetration in young
      transplants and then later for sustainable biocontrol of root-knot under field
      conditions are discussed.

PMID- 15149102
TI  - The use of olive mill wastes for the control of root-knot nematodes.
AB  - The suppressive effect of olive mill wastes was tested in a field experiment in
      sandy soil, infested by Meloidogyne incognita, in the Province of Lecce, southern
      Italy. The field was subdivided in 12 m2 plots distributed at random in four
      blocks. Treatment consisted of different dosages (10, 20 and 40 t/ha) of two
      composts prepared with either exhausted or fresh olive pomace or raw extraction
      sewage at rate of 40 or 80 m3/ha. There were four untreated control plots and
      four plots on which the granular 5% formulation of fenamiphos had been broadcast
      incorporated into the soil at the rate of 300 Kg/ha, one week before planting the
      tomato cv. Tondino di Zagaria. All treatments statistically increased tomato
      yields with respect to the control. Conversely, the root gall index, assessed
      according to a scale from 0 (no gall at all) to 5 (root system of reduced size
      and deformed by large galls), was significantly reduced in all treated plots.
      Also soil populations of the root-knot nematode declined, significantly compared
      to the control, except in the soil treated with the lowest doses of raw sewage or
      exhausted pomace compost.

PMID- 15149103
TI  - Study on interaction between root-knot nematode Meloidogyne javanica and wilt
      fungus Verticillium dahliae on olive seedlings in greenhouse.
AB  - Verticillium dahliae has been reported as a limiting factor in cotton, olive,
      potato and tomato fields from several countries in the world. Root-knot nematodes
      Meloidogyne javanica causes considerable damage to olive groves in olive growing
      areas. Since the presence of these two pathogens in olive trees and seedlings
      were confirmed in Golestan Province, this study was proposed to find the mode of
      their action and interaction with olive seedlings in greenhouse. The non
      defoliant strain of the fungus (SS-4) was isolated from olive groves showing
      symptom in Golestan Province. M. javanica was also recovered from the infested
      olive seedlings. After species identification, it was reared on tomato seedlings
      var. Rutgers. The larvae were used as a source of inoculum. Conidia and
      microsclerotia of V. dahliae were used as a source of inoculum for pathogenesis
      in this study. Stem cuttings of olive cultivar Zard were transplanted in
      different sets of pots containing 720 ml. of sterilized loamy soil and sandy
      soil. Experiment was conducted in Completely Randomized Design with 6 treatments
      and 8 replicates including control, nematode alone, fungus alone, nematode and
      fungus simultaneously, nematode and fungus concomitantly, fungus two weeks prior
      to nematode, nematode and fungus concomitantly, nematode two weeks prior to
      fungus. Pots were inoculated with 1500 larvae of nematodes and 7200
      microsclerotia of V. dahliae. Experiment was terminated after 9 months and
      following parameters were determined i.e. fresh weight of roots, number of galls
      and females, per root system and discoloration of leaf and root tissues. Presence
      of nematode prior to fungus caused reduction in colonization of fungus in the
      roots and the stems and vis presence of fungus prior to nematode caused reduction
      in number of galls produced by nematode. Sever symptom on aerial parts of plant
      was observed when both pathogens were inoculated simultaneously. However fresh
      weight of roots was reduced in all treatments. Galling and population density in
      root system were higher in pots filled with sandy soil than in loamy soil, but
      fungal colonization in roots and stems was much more in seedlings grown in loamy
      soil and diseases symptoms in aerial parts of plants were much severe in plants
      grown in loamy soil than in pots with sandy soil.

PMID- 15149104
TI  - Risk assessment of biocontrol products: a semi-selective medium for improving
      quantitative isolation of Paecilomyces lilacinus (strain 251) from soil.
AB  - Paecilomyces lilacinus (Thom) Samson 1974 is an egg pathogenic fungus, attacking
      mainly sedentary stages of root-knot and cyst nematodes, especially eggs, and is
      about to register as a product for the biological control of nematodes.
      Monitoring P. lilacinus (strain 251) is essential by way of ascertaining the fate
      and behaviour of this fungus in the soil. In order to obtain more data on the
      persistence of P. lilacinus (strain 251) in the soil, an improved selective
      medium for this strain is necessary. For this reason, different compounds with
      known antifungal properties were tested. Among them, P. lilacinus (strain 251)
      was found to tolerate high concentrations of 2,6-dichlor-4-nitroanilin, the
      active ingredient of Dichloran, which inhibits growth of many commonly occurring
      soil-borne fungi. The fact that P. lilacinus is more tolerant of higher salt
      concentrations than many other fungi are, was also taken into consideration. As a
      basis for the improved medium, OHIO-agar medium was used.

PMID- 15149105
TI  - The cytoskeleton in nematode feeding sites.
AB  - Sedentary edoparasitic nematodes induce specialised feeding cells in plant roots.
      Giant cells induced by root knot nematodes and syncytia generated by cyst
      nematodes in plant roots are large multinucleated cells containing a dense
      cytoplasm. To examine the plant cytoskeleton during feeding cell development,
      transcriptional activity of actin and tubulin genes and organization of the actin
      filaments and of the microtubules were analyzed in situ. Immunolocalizations of
      actins and tubulins and in vivo observation of green fluorescent protein
      decorated actin filaments and microtubules in nematode infected root cells
      revealed that major rearrangements of the cytoskeleton occur during the formation
      of nematode induced feeding cells.

PMID- 15149106
TI  - Biocontrol of Duponcheria fovealis (Lepidoptera: Pyralidae) with soil-dwelling
      predators in potted plants.
AB  - Duponchelia fovealis Zeller (Lepidoptera: Pyralidae) is a widespread pest in
      Dutch greenhouses. Most damage is recorded from potted plants as kalanchoe,
      cyclamen and begonia. Caterpillars of this pyralid prefer to live in a moist soil
      layer were they feed on either plant parts or organic matter. Larvae typically
      seek shelter within plant parts or in soil. This behaviour hampers contact
      between pesticides and caterpillars. Growers, therefore would welcome an
      effective method to prevent damage by D. fovealis. This paper describes the
      effects of the soil-dwelling mites Hypoaspis miles (Berlese) and Hypoaspis
      aculeifer (Canestrini) (Acari: Laelapidae) and the beetle Atheta coriaria Kraatz
      (Coleoptera: Staphilinidae) on eggs and larvae of D. fovealis. Both predatory
      mites and adults of the staphilinid beetle gave excellent control of eggs of D.
      fovealis in potting soil with kalanchoe. H. miles was slightly (99 percent
      control), but significantly, better than H. aculeifer (92 percent control). 50 to
      87 percent of the eggs were predated by adult beetles of A. coriaria. These
      beetles also prey on first larval stages of D. fovealis. 87 percent of the H.
      miles population was present in the upper soil layer, whereas about half of the
      population of H. aculeifer preferred to stay deeper than 5 cm in soil. This
      behaviour might explain the slightly better control of D. fovealis by H. miles,
      since eggs and first larval stages of D. fovealis are mostly present in the upper
      soil layer. All predators tested may contribute to an integrated or biological
      system for controlling D. fovealis in potted plants.

PMID- 15149108
TI  - Effectiveness of predators and parasitoids for the natural control of Diuraphis
      noxia (Homoptera: Aphididae) on barley in central Ethiopia.
AB  - The Russian wheat aphid, Diuraphis noxia (Kurdj.), is a serious threat for the
      production of barley, Hordeum vulgare L., in Ethiopia. The pest can cause up to
      100% yield losses in years of heavy infestation. Natural control of D. noxia by
      using predators and parasitoids might be the best alternative both from
      economical and ecological point of view. In this regard, a field investigation
      was conducted during the 2001 spring cropping season at Fitche, central Ethiopia
      to determine abundance of D. noxia and associated natural enemies and evaluate
      their effectiveness as natural control agents for this pest. In addition, the
      data collected during the 1995-1997 spring and summer cropping seasons at Chacha
      was analysed and presented. There was a highly significant difference (P < 0.01)
      on the population density of D. noxia between spring and summer and among
      sampling dates. The average aphid density was 23.1 and 0.7 aphids per tiller
      during spring and summer, respectively. The quantitative analyses based on
      predator units (PU) showed a highly significant difference (P < 0.01) among the
      predator groups, coccinellids and syrphids being more important, however, the
      coccinellid beetle, Hippodamia variegata Goeze, was the dominant species from all
      predator species or groups. Moreover, syrphid fly larvae were the only predators
      consistently found feeding on aphids within D. noxia rolled leaves. The
      polyphagous predators: Chrysopids, spiders and staphylinids were found to have
      less effect on D. noxia populations. Only two primary parasitoid species were
      recorded both during spring and summer cropping seasons: Aphidius colemani Vier.
      and Aphidius spp. Of these, A. colemani was more abundant in both seasons. The
      rate of parasitism was also generally low during the season. In general, the
      population build up of these natural enemies is slow and maximum population size
      is reached after the aphid population peaks and the crop has already been
      damaged. Further extensive work is necessary to maximize the effectiveness of
      natural enemies against this pest.

PMID- 15149107
TI  - Effect of aphid-infested plants on the host location and learning behaviour of
      the parasitoid Aphelinus abdominalis.
AB  - Aphelinus abdominalis Dalman (Hymenoptera: Aphelinidae) is a generalist
      parasitoid of cereal (e.g. Sitobion avenae) and greenhouse aphids (e.g.
      Macrosiphum euphorbiae). It differs from Aphidius spp. (Hymenoptera: Braconidae)
      by its robust constitution, longevity and its habit to use aphids not only as
      hosts for its progeny but also as prey (host feeding). In addition, A.
      abdominalis does not evoke Aphidius-characteristic defence responses by attacked
      aphids as this wasp approaches its hosts very carefully and then inserts its
      ovipositor nearly unnoticed by the aphids. In order to obtain more information on
      the host location behaviour of A. abdominalis, the effect of aphid-infested
      plants on its orientation and learning behaviour after mummy emergence was first
      studied in a series of Y-tube olfactometer experiments. When females reared on S.
      avenae were offered a 2 h foraging experience on M. euphorbiae-infested sweet
      pepper (Capsicum annuum) and then had the choice between the odour of uninfested
      sweet pepper plants and plants infested by aphid hosts (M. euphorbiae), they were
      significantly attracted to the odour of infested plants. Naive A. abdominalis,
      i.e. females that prior to the experiments were not offered any contact with a
      plant-host complex (PHC) after their emergence from S. avenae mummies and hence
      had no chance to learn the odour of the PHC, were not attracted by aphid-infested
      plants. The effects of adult experience on long-range host location by A.
      abdominalis (again reared on S. avenae) were then investigated in wind tunnel
      experiments by using M. euphorbiae-infested and uninfested sweet pepper and
      aubergine (Solanum melongena) plants. Females experienced with one of the offered
      PHCs significantly preferred the odour of the learnt PHC to that of the different
      PHC. A. abdominalis females obviously learn specific volatile signals emitted by
      aphid-infested plants for long-range host location.

PMID- 15149109
TI  - Methoxyfenozide, a reliable IPM compatible compound against Lepidoptera in pome
      fruit and vegetables with sterilising, ovicidal and larvicidal efficacy on
      codling moth.
AB  - Methoxyfenozide (Runner 240 SC), a Moulting Accelerating Compound (MAC) currently
      submitted for registration in Belgium, is an IPM (Integrated Pest Management)
      compatible compound with strong, broad spectrum activity against lepidopterous
      pests in pome frunit and vegetables. Field trials have confirmed reliable
      efficacy against larvae of winter moth O. brumata , both the overwintering and
      summer generation of the summer fruit tortrix moth, Adoxophyes orana and also the
      tomato looper, Chrysodeixes chalcites. Methoxyfenozide can be applied in pome
      fruit from green cluster onwards, and due to its bee safety it can be used also
      during flowering. The high consistency obtained with methoxyfenozide on the
      overwintering caterpillars of fruit tortrix moth relates in part to its minimal
      temperature dependence, to its high rain fastness and to the high intrinsic
      activity (low EC50) and to the ability to control all larval feeding stages. The
      effects of a treatment of the hibernating generation of A. orana on the
      subsequent summer generations is discussed. By special caged trials (semi-field)
      the pest- stage specificity against codling moth Cydia pomonella was
      investigated. Applications of methoxyfenozide were made just prior to egg
      deposition, at peak of egg laying and at the black head capsule stage of the
      embryo of codling moth. Results revealed evidence of reduced fecundity of female
      moths and confirmed the outstanding larvicidal and ovicidal properties of the
      compound (Charmillot, 2001). Application from just before egg deposition to the
      black head stage in the eggs is recommended and the additional sterilising effect
      completes the activity profile of methoxyfenozide. Treated females show reduced
      egg deposition whereas treated males increase the percentage of sterile eggs.
      Reduced field performance of methoxyfenozide in orchards showing resistance to
      diflubenzuron (chitin synthesis inhibitor), supports the findings of other
      authors on the cross-resistance of MACs and diflubenzuron. It is recommended that
      such orchards are not treated with methoxyfenozide.

PMID- 15149110
TI  - The sex attractant pheromone of the oak processionary, Thaumetopoea processionea
      a field evaluation.
AB  - The sex pheromone of Thaumetopoea processionea has recently been described as a
      mixture of different isomers with (Z,Z)-11,13-hexadecadien-1-yl acetate as the
      major active compound. First trials have shown that traps baited with this
      compound attract male moths in the field. In the present paper we evaluate the
      use of pheromone traps under practical aspects. The traps can be very well
      applied to monitor the pest, but the devices have to be installed in the upper
      crown of the oak trees. It is possible to determine the seasonal flight pattern
      of the moths. Results of field trials in Germany suggest that the traps can be
      used to roughly estimate the degree of infestation.

PMID- 15149111
TI  - Integrated crop management of the lesser date moth Batrachedra amydraula Meyr.
      (Lepidoptera: Cosmopteridae) infesting some date-palm varieties in Egypt.
AB  - The present study was conducted during the two subsequent seasons of 2001 and
      2002 in El-Beheira Governorate, Egypt, to evaluate the efficiency of some
      agricultural practices on the incidence of the lesser date-moth, Batrachedra
      amydraula Meyr. (Lepidoptera: Cosmopteridae) on some date-palm varieties, i.e.
      Sammany, Hayany and Halawy. The studied agricultural practices, were: covering
      clusters of flowers with paper craft, covering date bunches with porous plastic
      cloth, thinning of bunches and/or diverging strands of bunches using special
      metal rings. The infestation percentages of the lesser date moth for each of the
      evaluated varieties indicated that Sammany had the lowest value (22.68) as
      compared with Hayany (37.42) and Halawy (53.16), successively. So, Sammany
      variety was more tolerable to the infestation than the other two varieties. In an
      attempt to explain such variations in the infestation by Batrachedra amydraula,
      determination of wax contents as well as the histological studies of the green
      fruits of each variety were conducted. Results revealed that tolerance of Sammany
      to the infestation was due to relatively higher wax content (0.420 g/10 fruits)
      than that of either Hayany (0.220 g/10 fruits) or Halawy (0.320/10 fruits),
      respectively. Moreover, the lowest infestation percentage in Sammany variety was
      attributed to the structure of the outer and inner layers of fruits tissues,
      which could be considered as natural barriers against the insect pest, causing a
      considerable reduction in its infestation. To know the effect of the studied
      agricultural practices on the quality of dates, the physical parameters of
      ripened fruits (length, diameter, thickness and weight), in addition to the
      chemical properties of the same fruits (P.H, T.S.S, T.S. and E.C.) were also
      determined. There is a correlation between the studied chemicals, morphological
      and histological characteristics of the fruits on one hand and the calculated
      infestation rates on the other one. The tested varieties showed that Sammany
      variety had the lowest value of T.S.S (20.40) in comparison to Halawy (30.2) and
      Hayany (35.6). Also, the estimated sugar values were 23.60, 28.10 and 30.40 for
      the Sammany, Halawy and Hayany, consecutively.

PMID- 15149112
TI  - Role of mites and thrips in the agrobiocoenosis of the soybean.
AB  - Soy beans dangerous pests are mites and thrips, that is why the present paper
      aims at the examination of the changes in their numbers and dominance relations
      of some varieties of different maturity groups. The small plot experiments were
      conducted in Kisalfold region with the following soybean varieties: early
      ripening Bolyi 38, Evans, McCall, middle ripening Bolyi 45 and late ripening
      Eszter, Zsuzsanna and Borza, in Mosonmagyarovar. Mites and thrips were collected
      every week with Berlese-extractor. It was observed that Tetranychus urticae Koch,
      the dominant mite species on soybean, developed its peak-numbers at the end of
      August. The number of mites was 20 % higher on the late ripening varieties, than
      on the early ripening ones. Predatory mites (Typhlodromus pyri Scheuten,
      Amblyseius andersoni Chant) and thrips (Scolothrips longicornis Priesner,
      Aeolothrips intermedius Bagnall) could not reduce the number of Tetranychus
      urticae due to their low density. Among the thrips Thrips tabaci Lindeman was the
      main pest of the soybean leaves, but Frankliniella intonsa Trybom was dominant in
      the flowers. The blooming of the soybean primarily influences the dynamics of
      phytophagous thrips. The peak-number of pests reached the highest rate a week
      later and more thrips were counted on the late varieties as well. Early ripening
      soybean varieties are recommended to be grown in the Kisalfold region since they
      are less affected by mites and thrips.

PMID- 15149113
TI  - Data on the biology of cabbage stem flea beetle, Psylliodes chrysocephalus
      (Linnaeus, 1758) (Coleoptera, Chrysomelidae, Alticinae).
AB  - Biology of Psylliodes chrysocephalus (Linnaeus, 1758) known as pest of rape and
      other cruciferous crops in Europe was studied under field and laboratory
      conditions in Western Hungary. Oviposition usually takes place from the end of
      September through winter until the end of March. The number of eggs laid by a
      female may nearly be one thousand. The longevity and the rhythm of the
      oviposition depend on the climatic conditions. In most years the second (L2) and
      third (L3) developmental stage larvae over winter in the sterns and main ribs of
      the lower leaves of rape. In gentle winters first (L1) developmental stage larvae
      can also over winter because oviposition occurs during winter months as well.
      Adults also over winter, they live until the beginning of April of the next year.
      The larvae feed inside of the sterns and midribs of rape leaves; moulting also
      takes place there. At the beginning of May the fully developed larvae leave the
      plant and enter the soil to pupate. Adults of the new generation appear on the
      surface by the end of May and begin to feed on green pods of rape but, however,
      they also chew the leaves and sterns. After the harvest of rape adults are still
      active. Before going into summer diapause they visit cruciferous crops or various
      cruciferous weeds for feeding. Summer diapause takes places from the beginning of
      July until the end of August. On the basis of our investigations Psylliodes
      chrysocephalus (Linnaeus, 1758) has one generation a year in Hungary.

PMID- 15149114
TI  - Biological control of greenhouse whitefly (Trialeurodes vaporariorum) with fungal
      insecticides.
AB  - The influence of the biological insecticide Botanigard (Beauveria bassiana) on
      different developmental stages of the greenhouse whitefly (Trialeurodes
      vaporariorum) has been tested and compared with the influence of Preferal
      (Paecilomyces fumosoroseus), also a biological product. Six experiments were set
      up to test the two products on eggs, which were four and seven days old, on
      larvae of the first, second/third and fourth stage and to test the effect on egg
      deposition. These experiments were all conducted on cucumber. Egg-deposition was
      limited to a small area on the leaf by using leaf cages. To evaluate these tests
      the number of eggs or larvae developed to the next stage has been counted and
      compared to the total amount of eggs or larvae on the leaves. The results
      revealed that Botanigard has an effect on the larval stages. The first larval
      stage is most sensitive; the next stages have a decreasing sensitivity. There was
      no influence on the hatching of the eggs, but a treatment short before the
      hatching could have a residual effect on the new nymphs. When the treatment with
      Botanigard is performed shortly before a moult or a fungicide treatment, the
      efficacy of the product decreases significantly. The influence of Preferal on the
      greenhouse whitefly is, under the same circumstances, less obvious.

PMID- 15149115
TI  - Control of the two-spotted spider mite (Tetranychus urticae Koch) in glasshouse
      roses.
AB  - Populations of the two-spotted spider mite, Tetranychus urticae, can increase
      rapidly in glasshouse production, especially during summer. Both chemical and
      biological control must start at low densities for effective control. The
      combined efficacy of Phytoseiulus persimilis and the predatory midge, Feltiella
      acarisuga to control T. urticae on roses was evaluated in 2002. A second year
      rose crop (Rosa hybrida cv. First Red) was used for this experiment. Two
      glasshouse compartments of 200 m2 each were used, one was assigned for integrated
      control and the other for chemical control. The mite populations were monitored
      by bi-weekly analysis of 12 randomly selected harvestable flower stems, extracted
      on the Berlese funnel. Sticky plates (3 yellow and 3 blue/200 m2) were used for
      monitoring the Feltiella adults. End of January a population of +/- 2 spider
      mites/flower was present in both compartments. In the integrated control, the
      first Phytoseiulus were released on February the 7th, while the first release of
      Feltiella was on February the 20th. From week 7 till 13 the population of T.
      urticae increased exponentially to 90 spider mites/flower stem, while
      Phytoseiulus population was below one/flower stem. A treatment of fenbutatinoxide
      + hexythiazox (Torque + Nissuron) was necessary to reduce the spider mite
      population. A maximum number of predatory mite (4/flower stem) and predatory
      midge (106 adults/sticky plate) was found only 4 weeks later. A second increase
      of spider mite population occurred in week 27. Although 2 weeks later 3 predatory
      mites/flower stem were present, additional chemical treatment was necessary to
      control. A third and last increase of spider mite occurred in week 39. This last
      raise could be controlled effectively by Phytoseiulus and Feltiella. Chemical
      control in the second compartment was effective all-year-round with the exception
      of week 23 when a major increase up to 60 spider mites/flower stem was found. The
      applied biocontrol agents could not efficiently control spider mite in glasshouse
      rose. However, combined with selective insecticides they offer possibilities for
      IPM in glasshouse roses.

PMID- 15149116
TI  - Interaction between nutrient supplies and aphid numbers on potato (2001-2002).
AB  - We set up our experiment on 11 potato varieties with 4 treatments and 4
      replications in Hungary in 2001 and 2002. The aim of the experiment was to
      investigate the interaction between the nutrient supplies of potato and the
      change in the numbers of aphids feeding on the potato plant. In our experiment we
      sorted 4 nutrient levels according to the recommendations of soil analyses and
      variety holders. During the growing period we counted the numbers of aphids
      feeding on the potato leaves every week and controlled the virus infestation with
      ELISA-method after harvesting. Using the data we concluded that there is an
      interaction between the nutrient supplies of the potato plant and the numbers of
      aphids feeding on the leaves. The numbers of aphids on the plots with good
      nutrient supplies exceeded the numbers of aphids counted on the control plots. In
      2001 and 2002 we counted 1150 and 1205 aphids per 100 plants on plots with
      nutrient supplies in the peak time of swarming compared to the control plot with
      numbers of 799 and 978. Beside nutrient supplies weather conditions influenced
      the numbers of aphids, too. Different temperature and rainfall conditions in both
      years affected the intense and progress of swarming. This can be the reason for
      the appearance of the first aphids (in the last week of April in 2001 and in the
      first week of May in 2002) and the time of swarming (15-18 June in 2001 and 28-31
      May in 2002). Summer heat and hot days lowered the numbers of aphids. In 2002
      following the heat in June and July the population escalated. After harvesting we
      confirmed our hypothesis from the tuber samples by ELISA-method: The virus
      infestation was higher on plots with intensive growing practice than the virus
      infestation on the control plots. In 2001 the rate of PLVRV infestation on Agria
      variety of the control plot yielded 18.7%. At the time of the 3rd treatment it
      increased to 37.2%. In 2002 the control had an infestation rate of 12.6% and
      40.2% at the time of the 3rd treatment. In 2001 the rates of PVY infestation were
      15.2% and 23.4% respectively and in 2002 they were 14.8% and 18.2% respectively.
      As the interaction between nutrient supplies, changes in the numbers of aphids
      and the virus infestation are not yet well known, further experiments are
      required.

PMID- 15149117
TI  - The influence of methyl jasmonate and beta-glucosidase on induction of apple tree
      resistance mechanisms to two-spotted spider mite (Tetranychus urncae Koch.).
AB  - The objective of the research was to determine the influence of methyl jasmonate
      (JA-Me) and beta-glucosidase on the mechanisms of apple tree resistance to T.
      urticae like antibiosis and non-preference. The experiments were conducted on
      leaves of Close and Jester apple cultivars in laboratory conditions. Leaves were
      treated with: 1. solution of 0.1% JA-Me in 0.05% Triton X-100 (by spraying); 2.
      beta-glucosidase dissolved in 0.1 M citrate buffer at pH 6 (by petiole); 3. 0.05%
      solution of the Triton X-100 (by spraying); 4. 0.1 M citrate buffer at pH 6 (by
      petiole); 5. non-treated leaves. In the no-choice test, application of JA-Me on
      leaves of apple trees caused reducing of number of eggs laid up during three days
      of the experiment. In the choice test, which was carried out for determination of
      non-preference mechanism of resistance, there was not significant differences
      between number of mites on leaves treated with JA-Me compared to leaves treated
      with beta-glucosidase, and to non-treated leaves after 24 hours from solutions
      application. However, at the same experiment, females of T. urticae laid the
      least number of eggs on leaves treated with JA-Me. Analysis conducted using
      liquid chromatography method, revealed higher level of phenolic compounds on
      leaves treated with JA-Me compared to check and leaves treated with beta
      glucosidase. Thus, it appears that JA-Me may be regarded as elicitor of induced
      resistance of apple tree to two-spotted spider mite.

PMID- 15149118
TI  - Evaluation of tolerance of 20 wheat cultivars to Russian wheat aphid Diuraphis
      noxza (Mordvilko) at seedling stage under greenhouse conditions.
AB  - The Russian wheat aphid (R.W.A) is an aggressive pest of wheat, barley and other
      small grains in different parts of the world and during, the recent years in
      Iran. This aphid causes high damage, so that much insecticides have been used
      against it. At present time utilization of resistant varieties is one of the most
      important methods to control it. Therefore in order to evaluate the tolerance of
      20 wheat cultivars, seeds were planted in 18 cm diameter plastic pots and put in
      cages. One week after infestation the seedling foliage were cut and put in
      separate plastic bags, also roots were washed and put in other plastic bags.
      Number of aphids and plant heights and weights were analyzed based on ANOVA and
      treatment means were compared. The results indicated that the cultivars of
      yavaras, Arvand mutant, Bezostia and Alamut had a high tolerance at seedling
      stage.

PMID- 15149119
TI  - Testing of the attract and kill technique against Cydia pomonella in Croatia.

PMID- 15149121
TI  - Testing the efficacy of different insecticides to control onion thrips (Thrips
      tabaci Lindeman, Thysanoptera, Thripidae) in onion crops.
AB  - Onion thrips (Thrips tabaci) has become important pest in onion crops in
      Slovenia. Because it is a polyphagous species, it causes damage also in vegetable
      production in general (leek, cabbage, ornamentals etc.). The group of efficient
      insecticides for thrips control in Slovenia is limited, because its misusage in
      the past caused the development of resistance of this pest. In 2002, eight
      different insecticides based on four active substances was tested in Goriska
      region. The results of field experiments showed the highest efficiency of active
      substances Spinosad and Abamectine for control of Thrips tabaci. Unfortunatelly,
      they are not registrated in Slovenia for this purpose as yet.

PMID- 15149122
TI  - Laboratory evaluation of heavy metals stress on certain biochemical parameters of
      the aquatic insect, Sphaerodema urinator Duf. (Hemiptera: Belostomatidae).
AB  - The present work discussed the effect of lead and copper on certain biochemical
      parameters of the aquatic insect, Sphaerodema urinator, Duf. (Hemiptera:
      Belostomatidae). The insect samples were collected from fish farms of some
      volunteers. LC25 and LC50 were determined. The insects were exposed to three
      concentration levels (10, 20 and 30 mM) of lead nitrate and copper sulphate. The
      biochemical studies were carried out on the whole body homoginate. The results
      showed great reductions of the main metabolites (carbohydrates, lipid and
      protein). A decline in the alkaline phosphatase activity was detected, while an
      increase in the activity of acid phosphatase was found. Also the treated insects
      showed lower activities of GOT and GPT. In general, all estimated parameters were
      less than those of control.

PMID- 15149120
TI  - Topical toxicity of two acetonic fractions of Trichilia havanensis Jacq. and four
      insecticides to larvae and adults of Chrysoperla carnea (Stephens) (Neuroptera:
      Chrysopidae).
AB  - The toxicity of botanical origin compounds such as two acetonic fractions of the
      seed kernels of the Meliacea Trichilia havanensis Jacq with insecticide
      properties (azadirone (F12) and the mixture F18 [1,7+3,7-di-O-acethylhavanensin
      (4:1)], three insecticides commercially available (imidacloprid, natural
      pyrethrins+PBO, triflumuron) and phloxine B, were tested in the laboratory.
      Topical bioassays using third instar and newly emerged adults of the lacewing
      Chrysoperla carnea (Stephens) at the maximum field recommended rate in Spain for
      commercials and at 1,000 ppm of active ingredient for T. havanensis acetone
      fractions and phloxine-B, were carried out. Imidacloprid and triflumuron were
      very toxic to third instar larvae inhibiting adult emergence, being the rest of
      insecticides harmless. Fecundity and fertility were not affected by the non-toxic
      compounds. Concerning adults, only imidacloprid and natural pyrethrins killed
      them significantly 24 hours after treatment. Phloxine B, triflumuron and T.
      havanensis fractions were harmless and did not cause any effect on fecundity and
      fertility with the exception of triflumuron, which reduced considerably the egg
      hatch. It can be concluded that T. havanensis acetonic fractions and phloxine B
      were non-toxic to larvae and adults of C. carnea when treated topically, whereas
      triflumuron, natural pyrethrins and imidacloprid affected one or more of the
      evaluated parameters under our conditions.

PMID- 15149123
TI  - Laboratory evaluation of dimilin on growth and glutathione activity in
      mosquitofish, a non-target species.
AB  - Recently, dimilin was found to be effective on Culex pipiens (Diptera:
      Culicidae). Although considerable research has evaluated the efficacy of
      diflubenzuron, a benzoylphenylurea derivative, against target pest populations,
      impacts of this compound on nontarget organisms are comparatively unknown.
      Therefore, this study evaluate toxicity of dimilin (25% W.P), a trade formulation
      of diflubenzuron, on a larvivorous non-target species, Gambusia affinis (Pisces,
      Poeciliidae). The compound, applied for 24h at a concentration of 78 ng/l
      corresponding to the LD90 obtained against the fourth instar larvae of C.
      pipiens, was first tested on growth and development of G. Affinis by measuring
      some morphometric indexes. Results showed that dimilin caused a significant
      (p<0.01) reduction in both the length and the weight of juveniles. It had no
      significant effect on the gonadosomatic index and the condition index (K)
      measured in adult females. A significant reduction in hepatosomatic index was
      only observed at day 30 during the exposure. In addition, the body level of
      glutathione was also determined in order to provide information on their
      toxicity. Treatment resulted in a significant reduction in both the amount of
      ovarian proteins and the level of body glutathione starting day 15 compared to
      controls of the same age.

PMID- 15149124
TI  - Comparative effects of some ecdysteroid agonists in mealworms: ecdysteroid
      amounts and protein analysis in developing ovaries under in vivo conditions.
AB  - Some ecdysteroid agonists (RH-0345, RH-5849, RH-5992) were tested topically (10
      microg/female) on newly emerged adult females of mealworms under in vivo
      conditions. In a first series of experiments the compounds were assayed on
      ovarian ecdysteroid production measured at day 2 and 4 following treatment,
      corresponding to the beginning and the end of vitellogenesis. All tested
      compounds resulted in a significant increase in ovarian ecdysteroid amounts. RH
      5992 and RH-0345 were more active than RH-5849. In a second series of
      experiments, the activity of the compounds was investigated on ovarian proteins.
      The ecdysteroid agonists caused a significant reduction of protein amounts in the
      ovaries, and electrophoretic separation of ovary extracts from treated series
      showed that one or two bands were missing. These observations may an interference
      with the vitellogenesis process.

PMID- 15149125
TI  - Research on the influence of red deer (Cervus elaphus L.) grazing on grassland
      production in the south-eastern part of Slovenia.
AB  - Almost 60% of Slovenian territory is covered by forests and only Finland and
      Sweden are known as the more forest abundant countries in Europe. Among game that
      intensifies difficulties in the field of agricultural production, especially in
      north-eastern and south-eastern parts of the country, roe deer (Capreolus
      capreolus L.), wild boar (Sus scrofa L.) and red deer (Cervus elaphus L.)
      prevail. Negative impact of game on agricultural production in the above
      mentioned parts of Slovenia has risen significantly in the last decade. The data
      about the population density of game in Slovenia is often based on the payments
      of their damage on the cultivated plants that are usually performed by the
      hunting societies. Grassland represents around 60% of agricultural land in
      Slovenia, and herbage is a very important component of the red deer diet. At the
      forest border where ruminant ungulate animals spend most of their life, the
      grassland production for a farmer is often decreased because of the grazing of
      this hoofed animal. Hitherto, decrease of grassland productiveness from a
      farmer's perspective, caused by the red deer grazing, was not yet researched in
      Slovenia. Similar studies were also very rare in other European countries. With
      the intention of gathering data and learn more about the potential harmfulness of
      the red deer on grassland production the experiment was performed in the south
      eastern part of Slovenia in the year 2002. The influence of red deer grazing on
      grassland production for forage conservation at the forest border during the
      vegetation period was studied on three locations (Mala gora, Cvislerji and
      Mackovec) in the Kocevje region. The experiment lasted from the third decade of
      March until the first decade of October. Portable cages of size 1x0.5x0.5 m were
      used to exclude red deer from grazing the herbage. At four sampling dates in the
      season herbage air dry matter (DM) yield was measured at three different
      observations (cage-protected plot, cage-protected plot only two to three weeks
      before sampling date, otherwise freely grazed--removed and unprotected plot). The
      results from the experiment showed us that red deer grazed on grassland through
      all seasons and that the regeneration capability of sward was the highest in
      summer, middle in spring and smallest in autumn. On unprotected plots an average
      50% reduction of herbage DM yield was found with the most distant sites also up
      to 80% reduction.

PMID- 15149126
TI  - Evaluation of resistance in Amaranthus quitensis Kunth populations to imazethapyr
      and other imidazolinones.
AB  - Six populations of Amaranthus quitensis (R1, R3-R7), taken from soybean fields in
      Cordoba (Argentina), continuously treated with imazethapyr escaped from control
      with this herbicide. In order to characterize this resistance, whole plant assays
      were carried out using imazethapyr. Treatments were made at different doses, from
      0.5 g a.i.ha(-1) to 60 g a.i.ha(-1), at 200 1 ha(-1) and 200 kPa pressure. Shoot
      fresh weight was mesured 21 days after treatment. The results were expressed as
      resistance factor (ED50(R)/ED50(S)). Different degrees of resistance were found
      as its shown by the respective resistance factors: R1:22.5, R3:6.5, R4:43.1,
      R5:8.6, R6:4, R7:5. Due to the high variability in the response to imazethapyr
      treatments shown in some populations, and according to previous investigations on
      the ALS gene that proved heterozygosity a screening was made, at the recommended
      dose of imazethapyr. Plants were classified according to their state, dead, alive
      and affected (fallen but alive). Populations 3, 6 and 7 showed an important
      heterozygosity. Furthermore, in order to evaluate the existance of a possible
      cross-resistance, the recommended doses of 4 other imidazolinones (imazametabenz,
      imazapyr, imazamox, imazaquin) were applied to the plants. All populations were
      susceptible to both imazamox and imazapyr and showed cross-resistance to
      imazamethabenz and imazaquin.

PMID- 15149127
TI  - Is it possible to detect Echinochloa spp. tolerance to ACCase-inhibiting
      herbicides using a simple quick tolerance test?
AB  - The objective of this work was to evaluate the reliability of one quick tolerance
      test that would enable us, in only six days, to quantify tolerance levels of one
      biotype to one or more herbicides. For this purpose, we evaluated tolerance
      levels to cyhalofop-butyl of five Echinochloa spp. biotypes: muricata, crus
      galli, crus-pavonis, oryzicola and utilis, with unknown records of herbicide
      treatment. Moreover, two biotypes of Echinochloa phyllopogon were tested, one of
      them resistant (R) to fenoxaprop-P-ethyl and the other one susceptible (S). The
      Oryza sativa Puntal var. and Oryza sativa var. (wild rice) were also checked in
      order to demonstrate cyhalofop-butyl selectivity profiles. The assays were
      conducted with petri-dishes where, over the following increasing doses, fifty
      seeds per biotype and dose, were placed in each one: 0, 3, 6, 12, 18, 24, 48 and
      60 ppm of cyhalofop-butyl and codacide oil adjuvant. Six days later, the
      following parameters were evaluated: plumule length, root length, germination (%)
      and fresh weight reduction (%). E. muricata germination was reduced by 50% with a
      6 ppm dose. A non linear relation dose-germination was observed in the rest of
      the biotypes. The plumule length permitted the ranking of the biotypes into three
      groups: (1) resistant (E. phyllopogon R) or very tolerant (Oryza sativa Puntal
      var. and wild rice), those with a reduction of less than 30%, (2) tolerant,
      between 30 and 60% (E. oryzicola), and (3) susceptible, with a reduction of over
      80% (E. muricata, E. crus-galli, E. crus-pavonis, E. utilis and E. phyllopogon
      S). Only Oryzo sativa and E. phyllopogon R had a minimal reduction of fresh
      weight (less than 15%). The assays were repeated with whole plants and we checked
      the accuracy of this test that indicated the resistance level of one biotype in a
      quick, reliable and economic way.

PMID- 15149128
TI  - Cross resistance to ALS-inhibiting herbicides in Euphorbia heterophylla L.
      biotypes resistant to imazethapyr.
AB  - The effect of weeds on the diminution of agricultural production is considered to
      be between 30 and 50%. Imazethapyr is a herbicide which acts on the enzyme ALS,
      the first common enzyme in the biosynthetic pathway of valine, leucine and
      isoleucine. Euphorbia heterophylla is a common species in soybean fields in
      Brazil and different populations resistant to herbicides of the sulfonylurea and
      imidazolinone groups are currently being reported. The objectives of this work
      were: to determine the resistance of three different biotypes named RI, RII and
      RII to the herbicide imazethapyr: to establish the level of resistance to this
      herbicide, and to evaluate the behaviour of the biotypes to other herbicides with
      a similar mode of action. The response of plants treated with imazethapyr
      confirmed the existence of resistance in the biotypes denominated as RI, RII and
      RIII. The imazethapyr concentration required to reduce the activity of the enzyme
      ALS by 50% (I50) should be greater than 500 microM for biotypes RI, RII and RIII
      and 39.47 microM for the susceptible biotype. Applications made in the greenhouse
      at field doses of ALS inhibiting herbicides showed cross resistance in the case
      of imazamox and imazamethabenz but not in the cases of the other ALS inhibitor
      herbicides used. ALS activity results demonstrated that the imazethaphyr
      resistance in different biotypes of E. heterophylla is target site mediated.

PMID- 15149129
TI  - Bromus species in winter wheat-population dynamics and competitiveness.
AB  - The infestation of Bromus species in small grains, especially in winter cereals
      has increased over recent years. In some areas winter wheat growers consider
      Bromus spp. as their worst grass weed. Besides yield reduction, Bromus spp. cause
      lodging and complication of harvest. In Germany the two most dominant species are
      Bromus sterilis (L.) and Bromus secalinus (L.). In order to develop control
      strategies the population dynamics of the weeds were investigated. Based on the
      results a deterministic mathematical model using differential and algebraic
      equations was used to estimate changes in the population of the two Bromus
      species.

PMID- 15149130
TI  - Influence of application volume on herbicide efficacy.
AB  - Herbicide doses used by farmers are often lower than registration doses. One of
      the reasons put forward is that field assays for registration are performed at
      relatively high application volumes (typically 300 L ha(-1)), whereas farmers use
      lower volumes (down to 75 L ha(-1) or even lower). The resulting concentration of
      the active ingredient(s) and the formulants is supposed to enhance efficacy. To
      test this hypothesis in the case of specific graminicides, we compared the
      efficacy of clodinafop-propargyl and fenoxaprop-ethyl on Avena sativa at two
      application volumes. Fenoxaprop-ethyl was more efficacious when applied in 75 L
      ha(-1) as compared to 300 L ha(-1); ED95 were 20.0 and 26.0 g ha(-1),
      respectively. By contrast, clodinafop-propargyl exhibited the same efficacy under
      both conditions. Studies of dynamic surface tension showed differences in
      behaviour between spray dilutions of the two herbicides, especially at
      concentrations corresponding to ED95s. After 100 ms, surface tension decrease was
      lower than 2 mN m(-1) for clodinafop-propargyl at both application volumes. By
      contrast, surface tension decrease was 7 mN m(-1) for fenoxaprop-ethyl at 300 L
      ha(-1), and 18.5 mN m(-1) at 75 L ha(-1). In the case of fenoxaprop-ethyl sprayed
      at doses used in the practice, the retention of active ingredient by Avena sativa
      was lower at high application volume. This study shows that in some cases,
      concentration of the spray dilution may increase efficacy, formulation being
      probably involved.

PMID- 15149131
TI  - Critical period of weed control in oilseed rape in two Moroccan regions.
AB  - The determination of critical period of weed control in oilseed rape is necessary
      to know the weed control period. To determine the critical period, two fields
      experiments were carried out during 1995-96 growth season in Loukkos and Sais
      regions at two oilseed densities (D1 = 24 and D2 = 36 plants m(-2)). Ten
      treatments corresponding to plots left weed free or weeded plots until four
      leaves, flowers bud, flowering, puds formation, and maturity stages of oilseed
      rape were tested. Density and biomass of weeds were determined at each oilseed
      stages. Results showed that weed density and biomass were higher in Sais than in
      Loukkos sites. For a 10% yield loss, critical period of weed control in Loukkos
      was from 458 to 720 degree days after emergence (D degrees AE) and from 480 to
      720 D degrees AE in oilseed conducted at densities D1 and D2, respectively. In
      Sais, critical period of weed control was from 474 to 738 D degrees AE and from
      468 to 675 D degrees AE in oilseed conducted at D1 and D2, respectively. It was
      concluded that the length of the critical period of weed control in oilseed rape
      grain yield seems to be dependant of the level of the infestation.

PMID- 15149132
TI  - Study on the weed-crop competition for nutrients in maize.
AB  - Considering the effect of crop-weed competition the rate of weed growing, the
      competitiveness of the occurring weed species and the duration of competition are
      determining factors. Experiments were carried out on fields in order to collect
      data on the effect of early weed competition on maize, including the competition
      for nutrients and the possible rate of nutrient removal by weeds. From 7 sampling
      areas of the 9.2 ha field weeds and maize samples were collected 1 month after
      the sowing of maize. We determined the total numbers and the species numbers of
      weeds by plots. The removed plant species and maize were weighed then dried until
      the weight balance was reached. The samples were tested for N, P, K and Ca.
      Comparison was done with the weight and nutrient element content of maize plants
      taken from the treated, weed-free area. At the same time comparative analyses
      were made with the mass and nutrient contents of maize plants. There were 12
      occurring weed species in this experiment. Based on the rate of weed cover the
      following species were dominant: Datum stramonium L., Cannabis sativa L.,
      Amaranthus chlorostachis Willd., Chenopodium album L., Chenopodium hybridum L.
      Our experiments revealed that in the areas being likely to produce high weed
      populations and showing a considerable high nutrient removal by weeds, the
      competition between weed plants and maize occurs at an earlier stage of the
      vegetation period of maize than on fields with moderate weed populations. Weeds
      have utilised significant amount of nutrients which has been many fold of maize
      in case of unit area.

PMID- 15149133
TI  - Study of the selectivity of PRIMSTAR (fluroxypyr + florasulam) in two key grass
      species (FESRU & LOLPE) grown for seed production.
AB  - PRIMSTAR is a SE (Suspo-Emulsion) formulation containing 2.5 g florasulam & 100 g
      fluroxypyr-MHE per liter. PRIMSTAR is registered in Belgium since beginning 2003
      as selective herbicide to control the most important broadleaved weeds in wheat &
      barley. The weed-spectrum of this product is now completely evaluated.
      Nevertheless, it was interesting to study this product in grass seed production.
      The prime objective of this study was to investigate the crop safety of PRIMSTAR
      applied on the two key species of grass produced for seed. The two species in the
      study were: 1) FESRU--Creeping fescue Festuca rubra rubra cv. NEVSKI sown at 15
      kg/ha, June 6, 2001. 2) LOLPE--Perrenial ryegrass Lolium perenne cv. MERBO sown
      at 17.5 kg/ha, October 5, 2001. The trial was a randomized complete bloc design
      in 4 reps. The contractor was REDEBEL, a GEP registered independent company. The
      trial site was located in Melle, Belgium. TREATMENTS: PRIMUS 100 mL, PRIMUS 200
      mL, PRIMSTAR 1.05 L/ha, PRIMSTAR 2.1 L/ha, BASAGRAN DP 3 L/ha, BASAGRAN DP 6
      L/ha. The treatments were applied March 29, 2002 on a maintained weed-free field.
      CONCLUSION: PRIMSTAR appeared to be highly selective in FESRU & LOLPE intended
      for seed production. All evaluations observed were positive. Only some light
      visual crop injuries were possible, but mostly negligible and the symptoms
      disappeared very soon within 35 DAA. Treatments with PRIMSTAR had no effect at
      all on the main seed yield characteristics i.e. seed yield, thousand seed weight
      and germination power. Treatments with the reference BASAGRAN DP (bentazone +
      dichlorprop) brought about a more aggressive action in comparison with the
      PRIMSTAR treatments in terms of vegetative crop inhibition (reduced straw yield
      for perennial ryegrass).

PMID- 15149134
TI  - Biotypes resistant to herbicides in paddy fields in the Iberian Peninsula.
AB  - A consequence of modern agriculture and its dependence on herbicides, is the
      appearance of resistant weed populations. The first case of resistance on the
      Iberian Peninsula was found in Portugal and it was in a population of Alisma
      plantago-aquatica, resistant to bensulfuronmethyl, an ALS-inhibitor. For the same
      herbicide, control problems with Cyperus difformis were found in some Spanish
      rice fields. In the same rice field area, tolerance was observed in some
      Echinochloa spp. when auxinic herbicides (quinclorac) were used and some
      resistant Echinochloa spp. populations were found due to the long use of PS II
      inhibitors herbicides (propanil). The association of active ingredients, rotation
      of crops and adoption of mechanical control methods are the main strategies to
      combat resistance to herbicides.

PMID- 15149135
TI  - Cross-resistance to ACCase inhibitors of Lolium multiflorum, Lolium perenne and
      Lolium rigidum found in Chile.
AB  - APPs (aryloxyphenoxypropionates) and CHDs (cyclohexanediones) are two of the most
      important groups used post-emergence for the control of grass weeds. They inhibit
      the lipid synthesis in plants by interfering with the activity of the enzyme
      Acetyl-coenzyme A carboxylase (ACCase), acting at a meristematic level. The
      resistance patterns of the biotypes characterized seem to indicate the existence
      of different degrees of resistance. It is thus possible to identify biotypes
      presenting cross-resistance only to certain APPs, to APPs and CHDs, or only to
      CHDs. The objective of this work was to evaluate the cross-resistance to
      fenoxaprop-P-ethyl, fluazifop-P-butyl, propaquizafop, cyhalofop-butyl, haloxyfop
      R-methyl, tralkoxydim and tepraloxydim in three species of Lolium (L.
      multiflorum, L. perenne, and L. rigidum) resistant to diclofop-methyl. The assays
      were conducted with petri-dishes in which, over increasing doses, fifty seeds per
      biotype and dose were located in each dish. Two weeks later, the following
      parameters were evaluated: germination (%), number of roots, radicle length,
      plumule length, and fresh weight reduction (%). Based on plumule length and fresh
      weight reduction (%), diclofop-methyl resistant biotypes showed cross-resistance
      to fenoxaprop-P-ethyl, fluazifop-P-butyl, cyhalofop-butyl, haloxyfop-R-methyl,
      but not to propaquizafop, tralkoxydim and tepraloxydim. The parameters
      germination (%), number of roots or root length did not show a good relation
      between the dose and its efficacy (curves of dose response) for any of the
      susceptible and resistant biotypes studied.

PMID- 15149136
TI  - Alternative control of two biotypes of Echinochloa phyllopogon susceptible and
      resistant to fenoxaprop-ethyl.
AB  - Rice (Oryza sativa var.), is one of the most important crops worldwide, and is
      cultivated in the five continents since it adapts itself to all climatic
      conditions. The most important weeds that reduce the world rice yield are
      Echinochloa spp., annual gramineae, which, because of the selection pressure
      imposed on them, have developed resistance to a large series of herbicides. Two
      Echinochloa phyllopogon biotypes were studied, one of them resistant to molinate,
      thiobencarb and fenoxaprop-ethyl and the other one susceptible to these
      herbicides, both originating from California rice fields. In these biotypes, the
      effects of other herbicides were evaluated, some of them with the same mode of
      action [profoxydim (Aura) and cyhalofopbutyl (Clincher), both ACCase inhibitors]
      and others with different modes of action [quinclorac (Facet) belonging to
      auxinic herbicide families; bispyribac-Na (Nominee) and azimsulfuron (Gulliver),
      both ALS inhibitors]. The only herbicide that effectively controlled the R
      biotype was profoxydim (95% control). Cyhalofop-butyl, quinclorac and bispyribac
      Na did not control the R biotype by more than 40%. There is no doubt that
      azimsulfuron hardly had any effect (14%). On the other hand, in the S biotype,
      three herbicides were quite effective: profoxydim (93%), quinclorac (93%), and
      cyhalofop-butyl (90%). Bispyribac-Na and azimsulfuron hardly had any effect on
      the S biotype, with no significant differences in either herbicide (20%).

PMID- 15149137
TI  - Biodegradation of simazine in olive fields.
AB  - Simazine (2-chloro-4, bis ethylamino-1,3,5-triazine) is a herbicide of the s
      triazine group used mainly to control broad-leaved weeds in different crops.
      Several papers report about simazine and other s-triazine derivates as being
      actual polluting agents. In fact, simazine has been detected in groundwater and
      soil. Since this herbicide has been extensively used in Andalusia (south of
      Spain), we are analyzing the levels of simazine residues found in the soil of
      olive fields. We are also simazine could be detected isolating live micro
      organisms able to degrade this compound, and are characterizing the metabolic
      pathways leading to this degradation and the fate of this compound in nature.
      With all these data in mind, we will try to develop a strategy for the
      bioremediation of contaminated soils. We have taken samples of soil from many
      olive orchards of Andalusia that have been treated with simazine. These samples
      were located with the help of a handheld GPS. The presence of simazine of these
      samples was detected by HPLC. In most of the samples taken no, and those where it
      could be, contained very low levels of this herbicide (lower than 0.5 ppm). Soil
      samples are being characterized to determine their physicochemical
      characteristics [pH, organic matter, texture, etc), and we are attempting to
      correlate all these parameters with the presence or absence of simazine. From
      some of the soils, we have isolated a group of micro organisms that can grow
      using simazine as the sole carbon and nitrogen sources. We are analyzing how the
      addition of carbon or nitrogen can influence the rate of the simazine
      degradation.

PMID- 15149138
TI  - Evaluating non-equilibrum herbicides transport in undisturbed grassed buffer
      strips soil columns.
AB  - Possible contamination of water resources by applied pesticides (including
      insecticides and herbicides) is a problem currently. Grassed buffer strips have
      been considered to limit pesticide transfer to surface waters by reducing run-off
      and erosion. As reduction of run-off mainly involves infiltration in the grassed
      strip soils, possibility of groundwater contamination by rapid transfer of
      pesticides via the numerous root channels and macropores presents in grassed
      soils can not be excluded so far. The beneficial impact of high pesticide
      retention in the superficial horizons of these soils, related to their high
      organic matter content, could therefore be strongly reduced by the occurrence of
      preferential flows. Displacement studies on leaching of bromide (water tracer)
      and two herbicides, metribuzin (weakly adsorbed) and isoproturon (moderately
      adsorbed) were conducted in two undisturbed soil columns (length 30 cm, diameter
      14 cm) collected from La Jailliere (Loire Atlantique, France) under non saturated
      conditions. The infiltration fluxes, delivered through a rainfall simulator, were
      1.5 and 3 mm/h for one of the columns and 0.6, 1.5 and 3 mm/h for the second
      column. We obtained asymmetrical shapes of the breakthrough curves, with early
      breakthrough and increased tailing, qualitatively indicating the presence of
      preferential flow and confirming the risk of pesticide vertical transport through
      grassed strips superficial soil horizons. The results showed that leaching of
      both herbicides increased with the intensity of rainfall applied. This could be
      explained by a decrease of herbicides sorption due to a lower residence time in
      the soil.

PMID- 15149139
TI  - Botanical identification of several Echinochloa biotypes collected in Spanish
      rice fields with control failures of cyhalofop-butyl.
AB  - There is some disagreement about the species that constitute Echinochloa. Correct
      identification is agronomically and economically important because Echinochloa
      spp. are aggressive invaders and difficult to control. The identification of
      Echinochloa spp. is complicated because of the morphological diversity shown by
      the genus. This work was initiated because of the differential response to
      cyhalofop-butyl treatment shown by some populations of Echinochloa spp. Four
      biotypes were selected for botanical identification: two biotypes collected in
      the Seville area, one of them susceptible to cyhalofop-butyl (ED50 = 64 g a.i.ha(
      1)) and the other one tolerant (ED50 = 560 g a.i.ha(-1)), one tolerant biotype
      collected in the Badajoz area (ED50 = 420 g a.i.ha(-1)) and one tolerant biotype
      collected in the Valencia area (ED50 = 860 g a.i.ha(-1)). Botanical
      identification was carried out following Carretero's Keys (1981) on plants grown
      at the site of origin. The main distinguishable character of the species was the
      length of the upper glume. The following results were obtained: the susceptible
      biotype collected in the Seville area and the tolerant biotype collected in the
      Valencia area were characterized as Echinochloa oryzoides, the tolerant biotype
      collected in Badajoz was characterized as E. oryzicola and the tolerant biotype
      collected in Seville area as E. hispidula.

PMID- 15149140
TI  - [Chemical herbicidal treatment of turnips (Brassica napus L.) in Morocco].

PMID- 15149141
TI  - Effect of water stress on the agressiveness of oilsseed rape (Brassica napus L.)
      and two mustards (Sinapis alba L. and S. arvensis L.).
AB  - Oilseed rape (Brassica napus L.), a winter sown crop, may compete for water
      especially with Brassicaceae weeds. Investigating plant competition under water
      stress conditions is necessary for achieving a good yield in a Mediterranean
      climate characterized by a scarse water availability. This experiment was carried
      out to study the competiveness of oilseed rape (Brassica napus L.) with two
      brassicaceae weeds (Sinapis alba L. and S. arvensis L.). Species were grown at a
      density of two plants per bucket either in monoculture or as a binary mixture
      under water stress conditions in a greenhouse. Results of monoculture showed that
      B. napus had the highest shoot dry matter. Shoot dry matter of B. napus was more
      reduced by intraspecific competition than by interspecific competition due to S.
      arvensis. Shoot dry matter of S. alba in monoculture was higher than in mixture
      with S. arvensis, but more reduced in mixture with B. napus. In case of S.
      arvensis, shoot dry matter was more reduced by interspecific competition than by
      intraspecific competition. Agressivity based on grain yield showed, that B. napus
      was the most agressive species followed by S. alba. This agressivity did not
      change by the imposed water stress.

PMID- 15149142
TI  - Investigation of the effect of soil herbicides on the growth and nutrient uptake
      of potato.
AB  - In our experiments the effect of three preemergent herbicides was examined on
      potato varieties. The experiments were carried out under greenhouse conditions in
      pots with six Hungarian potato varieties. The following herbicides were applied:
      PATORAN 50 WP (metobromuron), SENCOR 70 WG (metribuzin) and COMMAND 48 EC
      (chlomazon). The results indicate that the variety Goliat showed the slowest
      growth. In the case of Lilla fresh and dry shoot weight was decreased by the
      application of PATORAN 50 WP and SENCOR 70 WG. Tuber weight showed a decrease
      with the application of SENCOR 70 WG in all varieties. The least tuber weight
      appeared with the varieties Kankan and Szozszorszep. Nutrient concentration of
      potato and N, P and K uptake by potato were examined. In the case of White Lady,
      Szazszorszep and Kankan N concentration and uptake increase significantly because
      of SENCOR 70 WG. There was a significant increase in phosphorus concentration and
      uptake in White Lady, Hopehely and Kankan varieties in all herbicide treatments.
      Potassium concentration increased in the case of all the six varieties because of
      herbicide treatments. Based on these experiments all varieties showed
      susceptibility against the used herbicides. The results show that important
      differences occur in the sensitivity and tolerance of varieties against
      herbicides, which are consequently significant for practical crop protection.

PMID- 15149143
TI  - Changes in nutrient content of Cirsium arvense (L.) Scop. during the vegetation
      period.
AB  - Cirsium arvense /L/ Scop. nowadays is popular in all territory of Hungary, it can
      be found almost on every soil types. Cirsium arvense is one of the most
      difficulty eradicated weed of the fields, the ruderals, and also the roadsides.
      On the base of IV. Hungarian Weed Survey 1996-1997, it takes the fifth place in
      the dominance sequence of the weeds, with 1.8% average covering. In the interest
      of effective weed control we can know the biological characteristics of the weeds
      in detail. In our experiments we followed the nutrient uptake and its changing in
      Cirsium arvense plants. Nitrogen concentration of shoots altered between 1.5
      3.6%. We established that plants can uptake potassium in a great quantity. Roots
      and shoots contained potassium in high concentration between 2.2-5.9%. The
      maximum of shoot production from the adventitious buds of the roots was in
      October and the minimum was in April and May.

PMID- 15149144
TI  - Chemical structure of mutagens and carcinogens and the relationship with
      biological activity.
AB  - Chemical carcinogenicity has been the target of numerous attempts to create
      predictive models alternative to the animal ones, ranging from short-term
      biological assays (e.g. mutagenicity tests) to theoretical models. Among the
      theoretical models, the application of the science of Structure-Activity
      Relationships (SAR) has earned special prominence. SAR has been applied both in a
      qualitative way (for example as simple recognition of suspected sub-structures or
      Structural Alerts), and in a quantitative way (Quantitative SAR, QSAR) to build
      mathematical models linking the physical chemical or structural properties of the
      molecules to the toxicological endpoints. This paper summarizes the contribution
      that the two approaches can provide in different situations. It concludes that
      the study of the structure of the chemicals generates predictions with limited
      reliability for the individual chemicals, however it has been demonstrated to be
      an extremely powerful tool for priority setting relative to large samples of
      chemicals.

PMID- 15149145
TI  - Accomplishments and perspectives of immunological interventions in
      lymphoproliferative disorders.
AB  - The purpose of this review is to consider evidences accumulated in the last few
      years which might lead to a new therapeutic strategy for lymphoproliferative
      disorders. Tumor-targeted and immunologically designed therapy has already
      started. Clinical effectiveness also includes the primary and secondary
      prevention of these malignancies. The fortifying of body's defense through
      vaccination as primary prevention with tumor-specific cell surface antigen, has
      been seen over the past few years, and will lead to health patient's improvement.
      Data collected from clinical trials and in vitro analysis indicated that the
      immune system of patients could recognize and eliminate neoplastic cells while
      sparing normal cells. In B-cell lymphomas and myelomas, the tumor-idiotype (Id)
      produced by a single B-cell clone, has been used for vaccination. Therapeutic Id
      vaccination used two types of antigen-presenting cells as natural adjuvants for
      the induction of antigen-specific T cell response. Dendritic cells (DCs)--based
      vaccines are under active investigation and are entering clinical evaluation.
      Current research focuses on optimization of DCs source, choice and loading of
      antigen, mode of injection, as well as immune monitoring. Some preliminary
      results were obtained and no significant side effects of dendritic cells
      vaccination of lymphoma and myeloma patients have so far been reported. The over
      estimation of clinical effectiveness, at this moment, is still limited by the
      small number of patients included in this kind of treatment. The challenge for
      the future will be to extend these early results to reproducible vaccination
      strategy according to current standards of good clinical practice (GCP).

PMID- 15149147
TI  - The combination of carboplatin and weekly paclitaxel: a safe and active regimen
      in advanced non small-cell lung cancer patients. A phase I-II study.
AB  - The combination of carboplatin and paclitaxel given every three weeks is a
      tolerated and reasonably active regimen in advanced non-small cell lung cancer
      (NSCLC). This study was designed to evaluate the maximum tolerated dose (MTD) of
      a fixed dose of carboplatin with an area under the curve (AUC) of 6 and
      escalating doses of weekly paclitaxel with an initial dose of 50 mg/m2 with 10
      mg/m2 increments at each level in untreated NSCLC patients (phase I study). The
      study continued with a phase II study. Thirty patients entered the phase I study.
      The MTD was: carboplatin AUC = 6 on days 1 and 28 plus paclitaxel 100 mg/m2 (1
      hour) on days 1, 8,15, 28. The dose-limiting toxicity (DLT) was severe
      neutropenia and cardiological toxicity. Subsequently, 42 patients entered the
      phase II study with the same treatment schedule. The 2-drug combination was
      globally well tolerated. The overall response rate (RR) was 42% [CI 95%: 26.3
      57.7], stable disease (SD) 29% and progression (PD) 29%. The median duration of
      response was 8.0 mos (range: 1.0-19.0). The median time to progression was 8.0
      mos (range: 7.0-19.0) and the median survival was 14.0 months (range: 9.0-19.0).
      The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to
      be manageable, active and extremely safe even in elderly patients (one third of
      all patients in our cohort). The survival results were interesting: the median
      survival time was 14 months (9-19 months) and the 1- and 2-year survival was 59%
      and 16%, respectively.

PMID- 15149146
TI  - Focus on the histologic diversity in primary and lymph node lesions and the
      outcome of gastric cancer.
AB  - According to the Japanese Classification of Gastric Carcinoma, one predominant
      type should be selected to represent the histology of the carcinoma. The authors
      investigated the relationship among the histologic variables of primary lesions,
      metastatic lesions and the outcome of patients. A total of 155 patients with node
      positive gastric carcinoma were examined. According to the histologic diversity,
      histologic grades were assigned from 1 to 4 regardless of the predominant
      histologic type. A larger number of histologic types composing not the primary
      lesions, but metastatic lymph nodes, were associated with an increasing frequency
      of advanced stage tumors. On the prognosis by number of histologic types
      composing the primary tumor and the metastatic lymph nodes, there were
      significant differences except between the histologic type-2 and histologic type
      3 groups in the only metastatic lymph nodes. In conclusion, patients with a
      greater number of histologic types composing lymph node metastases had poorer
      prognosis than with a small number of histologic types. Histologic diversity
      within metastatic lymph node was thought to be important for determining the
      prognosis of patients with gastric cancer.

PMID- 15149148
TI  - Patients with Paget disease of nipple and with palpable mass in breast have
      unfavorable prognosis.
AB  - Recent data indicate that in breast cancer patients the presence of Paget disease
      of the nipple may be related to poor prognosis. Therefore, we decided to assess
      long-term results of the treatment of such patients, and to assess the
      relationship between the physical and pathological findings and prognosis. The
      files of 60 patients with Paget disease of the nipple who were treated between
      1977 and 2000 were analyzed retrospectively with respect to the results of
      physical and pathologic examinations, disease recurrence and survival. In 38/60
      patients, the cancer was invasive. In 26/60 patients, palpable masses in the
      breast were diagnosed. The 5-year overall survival probability was 0.68; the
      probability was 0.82 for patients without palpable masses, 0.51 for those with
      palpable masses, 0.91 for patients without invasive cancer and 0.58 for patients
      with associated invasive cancer. In conclusions, patients with Paget disease of
      the nipple and with palpable mass in the breast had unfavorable diagnosis. The
      nature of all nipple changes should be explained as early as possible in order to
      diagnose the disease when no mass is palpable in the breast.

PMID- 15149149
TI  - Diffusion-weighted MR imaging in the evaluation of renal tumours.
AB  - The aim of this study was to evaluate the capability and the reliability of
      diffusion-weighted MR imaging to differentiate benign from malignant renal
      lesions. Twenty healthy volunteers and 48 patients with known renal lesions
      underwent MR of the kidneys by using a 1.5 T superconductive magnet. Diffusion
      weighted images (DWI) were obtained on the axial plane during breathhold (17 s)
      with a SE EPI single shot sequence using a b value of 500 s/mm2. One region of
      interest (ROI) (lesions < than 3 cm) or 3 ROI (lesions > than 3 cm) were placed
      within the lesion for the measurement of apparent diffusion coefficient (ADC).
      ADC map was obtained at each slice position. Mean ADC value in normal renal
      parenchyma was 2.2 +/- 0.20 x 10(-3) mm2/s, while ADC values in simple cysts (n =
      20) were higher (mean ADC values 3.65 +/- 0.09 x 10(-3) mm2/s). Solid benign and
      malignant renal tumors (n = 19) showed a mean ADC value of 1.7 +/- 0.48 x 10(-3)
      mm2/sec. The comparison between ADC values in normal parenchyma group and tumour
      group were found to be statistically significant (p < 0.0001). ADC values of
      cystic renal cell carcinomas were higher than those of clear cell carcinomas (p <
      0.001). In conclusion, DW MRI of the kidney seems to be a reliable means for
      differentiating normal renal parenchyma from different renal tumors.

PMID- 15149150
TI  - Successful treatment of refractory anemia with a combination regimen containing
      recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.
AB  - Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal
      malignancies. Patients belonging to the refractory anemia (RA) subtype are
      usually treated with recombinant human erythropoietin (EPO). Not all patients
      respond to EPO administration and they are strictly dependent on supportive
      therapy with red cell blood (RBC) transfusions. The aim of this study was to
      investigate the efficacy of an alternative combination regimen containing EPO,
      low-dose methylprednisolone and nandrolone decanoate, in patients with RA
      unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median
      age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO
      administration and RBC transfusion-dependent were included in the study. Median
      hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC:
      3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three
      times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and
      nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were
      administered. As complete response (CR) to treatment was considered the
      normalization of the peripheral blood and bone marrow smears and biopsy. As
      partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to
      10 g/dl and discontinuation of RBC transfusions. The response to therapy was
      evaluated on the 4th week after the initiation of the combination treatment. Bone
      marrow smear evaluation was carried out at baseline and every six months
      afterwards. After a 4-week treatment all patients achieved PR and discontinued
      RBC transfusions. Median and range hematological values on the 4th week after
      treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5
      6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values
      was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and
      PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment
      with the combination regimen, achieved CR one after six months and the second
      after 12 months. They are alive after 5 years from initiation of the combination
      treatment. After a median period of 18 months (range 12 to 20 months) in PR three
      men developed acute leukemia; they received intensive antileukemic chemotherapy
      without any response and died during the phase of pancytopenia. Three other men
      achieved CR, one after 6 and two after 12 months of therapy and they are on
      regular follow-up. Two women after 10 and 14 months in PR developed acute
      leukemia and died. In conclusion, combination therapy with EPO, nandrolone
      decanoate and low-dose methylprednisolone may be effective as an alternative
      treatment for RBC transfusion-dependent patients with RA unresponsive to EPO
      administration alone.

PMID- 15149151
TI  - Evaluation of hepatic metastases from colorectal carcinoma with MR
      superparamagnetic iron oxide.
AB  - The purpose of this study was to compare the results obtained with
      superparamagnetic iron oxide-enhanced and unenhanced Magnetic Resonance at 1.5 T
      with that of spiral-computed tomography (CT) in order to select those patients
      suitable for liver resection; the intraoperative US (IOUS) comprised the gold
      standard. Thirty five candidates for liver resection with known colorectal
      neoplasm were studied; 26 patients underwent surgery, one patient underwent RF
      ablation and 8 of them were submitted to follow-up. MR examination was performed
      using a 1.5 T superconductive instrument, CT examination was performed on a
      Somatom-Plus (Siemens) scanner. Dimensions and number of the lesions were defined
      in all patients as well as the sensitivity of spiral CT and MR imaging, using
      either the plain technique or after Ferumoxides c.m.. In those patients submitted
      to surgery, results have been correlated to those of IOUS. From 26 patients, a
      total of 48 lesions were removed surgically. With CT, 34 lesions with 3 false
      positive cases were detected; 32 with plain MR imaging, while MR imaging with
      Ferumoxides detected 41 lesions. In the patients not submitted to surgery, MR
      iron-oxide imaging identified 15 lesions, while both plain MR imaging and CT
      showed 8 lesions. The smallest lesion was 6 mm. as shown by MR imaging with
      Ferumoxides. In the cases submitted to surgery, the CT sensitivity was 71%, plain
      MR imaging 66% and MR imaging with Ferumoxides 85%. In our experience,
      Ferumoxides-enhanced MR imaging of the liver shows increased sensitivity compared
      to plain and spiral-CT in the evaluation of hepatic metastases. We think that MR
      superparamagnetic iron oxide should be used in all patients selected for liver
      resection.

PMID- 15149152
TI  - Antimutagenicity of herbal detoxification formula Smoke Shield against
      environmental mutagens.
AB  - Smoke Shield is a formulation designed to reduce smoke related mutagenicity and
      toxicity in the population. Smoke Shield contains a dual extract of turmeric
      (Curcuma longa) obtained by supercritical CO2 gas extraction and post
      supercritical hydroethanolic extraction together with extracts of green tea and
      other spices, whose presence synergistically increases the activity of turmeric.
      In the present study we have shown its antimutagenic activity to various
      environmental mutagens in vitro and in vivo. Smoke Shield was found to produce
      significant inhibition of mutagenicity to Salmonella typhimurium induced by
      sodium azide and 4-nitro-0-phenylenediamine (NPD) at a concentration of 2
      mg/plate while inhibition to N-methyl-N-nitro N'nitrosoguanidine was less
      significant. Inhibition was also found to depend upon the strain which was used.
      Smoke Shield was found to be more effective against mutagens needing metabolic
      activation such as 2-Acetamidofluorene (2-AAF) and benzo[a]pyrene. Smoke Shield
      was also found to significantly inhibit the mutagenicity induced by tobacco
      extract to Salmonella typhimurium TA102. Smoke Shield was also found to inhibit
      the urinary mutagenicity of rats treated with the benzo[a]pyrene and tobacco
      extract. Moreover, Smoke Shield administration was found to inhibit the urinary
      mutagenicity in smokers. These results indicate that Smoke Shield could inhibit
      mutagenic response in vitro and in vivo produced by several kinds of mutagens
      present in our atmosphere.

PMID- 15149154
TI  - The effects of locally injected granulocyte macrophage-colony stimulating factor
      on the healing of intraoperatively irradiated intestinal anastomoses in rats.
AB  - Intraoperative irradiation is used to reduce the number of local recurrences and
      to increase disease free survival in the treatment of intestinal malignancies.
      Irradiation for the local control of tumours diminishes the wound healing in the
      intestine as in any other tissues. For many surgeons, it seems too risky to make
      resection and anastomosis in an irradiated intestine. Granulocyte Macrophage
      Colony Stimulating Factor (Gm-csf) had been successfully used in chronic and
      incisional dermal wounds. In this study, we evaluated the effect of locally
      applied Gm-csf on intraoperatively irradiated rat small intestinal anastomosis.
      160 male Sprague-Dawley rats were randomized into 4 groups. In group 1 (control),
      ileal resection was made (1 cm. in length) and anastomosis was performed. In
      group 2, ileal resection and anastomosis were performed and 50 microgr. rHu Gm
      csf was injected subserosally in the perianastomotic area. In group 3,
      intraoperatively 2000 cGy irradiation was applied to the intestine following
      ileal resection and anastomosis. In group 4, ileal resection and anastomosis were
      performed, and 50 microgr. rHu Gm-csf was injected subserosally in the
      perianastomotic area, then intraoperatively 2000 cGy irradiation was applied to
      the intestine. On the 3rd and 7th days, relaparotomies were made in order to
      measure the bursting pressures of the anastomotic segments. The measurement of
      hydroxyproline levels were evaluated to determine the amount of anastomotic
      collagen. Histopathological evaluations were also performed. The bursting
      pressure values in gm-csf given groups were significantly higher than their
      control groups. The hydroxyproline content of group 4 was significantly higher
      than group 3 on the 3rd day. In conclusion, these data indicate that local
      injection of Gm-csf improves the wound healing of intraoperatively irradiated
      bowel anastomosis.

PMID- 15149153
TI  - Extract of vinegar "Kurosu" from unpolished rice inhibits the proliferation of
      human cancer cells.
AB  - The effects of the ethyl acetate extract of "Kurosu" (EK), Japanese traditional
      vinegar from unpolished rice, on the proliferation of a variety of human cancer
      cell lines were investigated by using the alamar blue assay. Cancer cell lines
      included colon adenocarcinoma (Caco-2), lung carcinoma (A549), breast
      adenocarcinoma (MCF-7), bladder carcinoma (5637), and prostate carcinoma (LNCaP)
      cells. EK inhibited the proliferation of all tested cell lines in a dose
      dependent manner, with inhibition mostly pronounced in Caco-2 cells (up to 62%
      inhibition at a dose level of 0.025%). Flow cytometry of EK-treated Caco-2 cells
      showed a decrease in cell number in the G2/M phase and an increase in the sub-G1
      phase (apoptotic). In addition, DNA fragmentation was detected in Caco-2 cells
      cultured with EK by immunostaining. RT-PCR analysis revealed p21 mRNA expression
      was induced in EK-treated Caco-2 cells. Moreover, PARP cleavage was promoted in
      EK-treated Caco-2 cells. These results suggest that EK causes G0/G1 arrest
      through p21 induction and, thus, is a potential apoptosis inducer in Caco-2
      cells.

PMID- 15149156
TI  - The in-vitro effects of medroxyprogesterone acetate on acidic pH induced
      apoptosis of periferal blood mononuclear cells.
AB  - Medroxyprogesterone acetate (MPA) which has a steroid structure, is widely used
      in oncology practice in the treatment of the cachexia of cancer and to reduce
      hematologic toxicity in patients receiving chemotherapy. However, the mechanisms
      of MPA on these effects are unclear. In this study, we investigated the effects
      of two different doses of MPA (10(-5) and 10(-6) M/L) on acidic pH induced
      apoptosis of periferal blood mononuclear cells (PBMC) derived from 10 healthy
      volunteers. Compared with the control group, we found that MPA at the dose of 10(
      5) M/L had a negative effect on apoptosis (32.88 +/- 4.61 and 20.7 +/- 1.53%
      respectively, p < 0.05), a positive effect on cell count of PBMC (1395 +/- 151 x
      10(3) and 1100 +/- 139 x 10(3) respectively, p < 0.05) and no effects on cell
      viability and its proliferation. More comprehensive trials are needed to clarify
      this effect of MPA.

PMID- 15149155
TI  - Induction of a multifactorial resistance phenotype by high paclitaxel selective
      pressure in a human ovarian carcinoma cell line.
AB  - Paclitaxel (PTX) is a potent anti-neoplastic agent that is highly effective in
      treating ovarian cancer. Nevertheless, the emergence of PTX resistance has
      limited the control of this disease. To gain insight into the molecular
      alterations accompanying drug resistance in ovarian cancer, we generated a new
      stable PTX-resistant ovarian carcinoma cell line. CABA I cells, which display an
      intrinsic PTX resistance (IC50 = 800 ng/ml), were subjected to continuous
      exposure to PTX. From the residual surviving cells, the highly PTX-resistant line
      CABA-PTX (IC50 = 256000 ng/ml) was generated and stably maintained in vitro.
      Analysis of beta-tubulin expression indicated that only the HM40 and Hbeta9
      isotypes were expressed in both parental and resistant cells. No specific point
      mutations in the HM40 were detected in either cell line, but expression levels of
      this isotype were significantly reduced (40%) in CABA-PTX cells. Hbeta9 levels
      were unchanged. In those cells, PTX resistance was associated with cross
      resistance to vinblastine but not to methotrexate or 5-fluorouracil. Verapamil
      treatment did not reverse the intrinsic drug resistance of parental cells, but
      partially modulated the sensitivity of CABA-PTX cells to PTX and induced total
      sensitivity to vinblastine. No changes in the cell surface expression of the drug
      efflux pumps MRP1, MRP2 and P-glycoprotein were observed. PTX influx, monitored
      using a fluorescent drug derivative, was significantly reduced and delayed in
      CABA-PTX cells as compared to the parental cells. Together, these findings
      suggest that more than one mechanism is involved in PTX resistance, making CABA
      PTX cell line a potentially valuable in vitro tool to study multifactorial
      acquired drug resistance in ovarian cancer.

PMID- 15149157
TI  - BCL-2 and P53 expression in endometrial carcinoma.
AB  - Our aim was to compare the results of bcl-2 expression in endometrial carcinoma
      with clinicopathological prognostic factors along with p53 accumulation. In
      addition, p53 expression was compared to different subtypes of endometrial
      carcinoma. Immunohistochemical staining was performed on formalin-fixed, paraffin
      embedded tissue sections by using Bcl-2 Supersensitive Mouse Anti-Bcl-2
      Oncoprotein (Biogenex AM287-5M) for bcl-2 immunostaining and Supersensitive Mouse
      Anti-p53 Suppressor Gene Product (1801) (Biogenex AM 240-5M) for p53
      immunostaining. 9 out of 9 cases of proliferative endometrium, 5/5 cases of
      endometrial hyperplasia without atypia, 5/5 cases with atypia, and 21/35 cases of
      endometrial carcinoma showed bcl-2 protein expression. Bcl-2 expression was not
      related to age, surgical stage, or histopathological features, nor was there an
      inverse correlation between bcl-2 and p53 expression in endometrial carcinoma.
      p53 expression was detected in 3/4 cases of serous papillary carcinoma, whereas
      only 5/31 cases of endometrioid carcinoma showed p53 expression. Bcl-2 expression
      decreased in endometrial carcinomas, and mechanisms other than p53 may play a
      role in the regulation of bcl-2 expression in endometrial carcinoma. Abnormal p53
      protein expression is an important event in the development of serous tumors,
      which may explain partly why they are more aggressive than their endometrioid
      counterparts where p53 expression does not play a major role.

PMID- 15149158
TI  - Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal
      intraepithelial neoplasia (DIN 1a).
AB  - Survivin is a recently discovered member of the family of proteins that inhibits
      apoptosis. This anti-apoptotic compound can be detected in most types of cancer
      and expression is associated with a poor prognosis. We, immunohistochemically,
      investigated the expression of survivin in breast carcinomas and intraductal
      epithelial neoplasia of the breast to determine whether expression of this
      protein is associated with clinicopathological parameters such as grade, stage,
      mitotic rate. In 34 out of 43 cases (79.1%) of breast carcinoma and 22 out of 62
      cases (35.4%) of intraductal epithelial neoplasia with mild, moderate and severe
      ductal epithelial, cell hyperplasia stained positively for survivin. None of the
      histological parameters analyzed were significantly correlated with survivin
      expression in breast carcinomas. In the carcinoma cases, survivin expression was
      positively correlated with expression of bcl-2, but was not correlated with
      expression of p53, bax, c-erbB-2 and estrogen, or progesterone. Some of the
      intraductal epithelial neoplasia cases with moderate or severe ductal epithelial
      hyperplasia stained positively for both survivin and p53. Breast carcinomas
      exhibited a significant expression of survivin, p53, and bcl-2 compared to breast
      with intraductal epithelial neoplasia. Survivin was not correlated with any of
      the clinicopathological parameters studied, however it could be a useful tool in
      early carcinomas and florid, severe ductal epithelial hyperplasia.

PMID- 15149161
TI  - Clinicopathologic significance of cyclin A expression in colorectal carcinoma.
AB  - The clinical significance of cyclin A expression, which has been known to act in
      the mitotic phase of the cell cycle, as an indicator of malignant potential in
      human tumors, has been suggested. The aim of this study was to elucidate the
      significance of immunohistochemical expression of cyclin A in colorectal
      carcinomas based on a larger study population. Immunohistochemical staining for
      cyclin A was performed for 167 colorectal carcinomas and the correlation between
      cyclin A expression and the clinicopathological characteristics was analyzed. One
      hundred and two carcinomas (61.1%) had cyclin A expression and the other 65
      (38.9%) did not. The mean size of the tumors with cyclin A expression was
      significantly larger than that of tumors without cyclin A expression (p = 0.012).
      Survival in patients with cyclin A-expressing carcinomas was significantly worse
      than that in patients with carcinomas without cyclin A expression (p = 0.004).
      Cyclin A expression (p = 0.030), as well as lymph node metastasis (p = 0.007) and
      Dukes' stage of the tumors (p < 0.0001) were found to be factors independently
      associated with unfavorable prognosis in patients with colorectal carcinoma. Our
      results demonstrated that immunohistochemical expression of cyclin A is an
      independent prognostic indicator in patients with colorectal carcinoma.

PMID- 15149160
TI  - An association between the matrix metalloproteinase 1 promoter gene polymorphism
      and lymphnode metastasis in breast cancer.
AB  - A single guanine insertion (1G/2G polymorphism) in the promoter of the matrix
      metalloproteinase (MMP-1) gene creates a binding site for the transcription
      factor and may affect the level of transcription of MMP-1. An elevated level of
      MMP-1 in cancer cells may facilitate their invasion and contribute to metastasis.
      To evaluate the contribution of 1G/2G polymorphism in the development and/or
      progression of breast cancer we genotyped 135 subjects with breast cancer. The
      1G/2G polymorphism was determined by the method based on restriction endonuclease
      digestion. We found that the frequency of the 2G allele was higher in lymphnode
      metastasis patients than in the group without metastasis (p < 0.001). We did not
      find differences between distribution of the genotypes and frequencies of alleles
      in cancer patients and in healthy subjects served as control. Our results suggest
      that allele 2G may be associated with lymphnode metastasis in patients with
      breast cancer and therefore it can be considered as a prognostic marker in this
      disease.

PMID- 15149159
TI  - Usefulness of polyclonal antibodies raised against P65 oncofetal protein in
      immunohistochemical diagnosis of ductal breast cancer.
AB  - Paraffin-embedded infiltrating ductal breast cancer tissue slides (135) were
      analyzed by immunohistochemistry with the use of rabbit polyclonal anti-P65
      oncofetal protein and mouse monoclonal anti-estrogen/progesterone receptor (ER,
      PR) antibodies. Analysis with anti-P65 antibody revealed the positive cytoplasmic
      reaction in 83 cases, 98 showed the nucleic reaction and 3 were immunologically
      negative. Among the analyzed cases 49 revealed both cytoplasmic and nucleic
      reactions. For the whole group of cancers the correlation was found between ER or
      PR level and P65 cytoplasmic reaction (r = 0.77 and 0.66, respectively) and low
      inverse correlation with nucleic localization of P65 protein. The percentage of
      positive cells with cytoplasmic expression of P65 was significantly higher in
      more histologically differentiated cancers (grade I and II according to Bloom and
      Richardson) than in grade III. Opposite tendency was observed for the nucleic
      expression of P65 protein. The percentage of immunopositive nuclei grew with the
      advance of the disease and was the highest in poorly-differentiated (grade III)
      tumors. The tumors with P65 cytoplasmic reaction were mainly small (T1, T2),
      without metastases to lymph nodes (N0) and distant metastases (M0). The
      dependence between P65 protein localization and clinical stage of disease (TNM
      classification) was evaluated statistically. The straight dependence existed
      between P65 nucleic reaction and tumor size (p = 0.0002), metastases to lymph
      nodes (p = 0.0032) and distant metastases (p = 0.0006). The obtained results
      suggest that the transfer of P65 protein from cytoplasm to nuclei of the breast
      cancer cells is connected with more clinically advanced stages and worse
      prognosis for the patients.

PMID- 15149162
TI  - PCR-array gene expression profiling of hepatocellular carcinoma.
AB  - Many trials using DNA microarrays have been reported for various human
      malignancies, but an efficient molecular diagnostic system has yet to be
      established. Here, we adopted a high throughput quantitative PCR-array system
      based on adaptor-tagged competitive PCR (ATAC-PCR), as a novel technique for gene
      expression profiling of hepatocellular carcinoma (HCC). This PCR-array contained
      3,072 genes derived from three different cDNA libraries, including 298 additional
      known genes suspected to be involved in hepatocarcinogenesis. Using this PCR
      array with 20 pairs of liver tissues (20 HCC, 20 surrounding nontumor liver), we
      identified a total of 117 genes differing in expression levels in the two liver
      tissues. Hierarchical clustering analysis and principal component analysis with
      these genes revealed distinct gene expression patterns in the HBV-positive group
      and the HCV-positive groups. Among 117 genes, only 7 (GPAA1, TMEM9, FACL4, ADFP,
      MAWBP, PACE4, FOS) were common to both groups. In conclusion, this PCR-array
      analysis with an appropriate set of genes is considered useful for gene
      expression profiling of HCC, and we identified some genes which may play a common
      key role in hepatocarcinogenesis.

PMID- 15149163
TI  - Isolated splenic metastasis from colon cancer.
AB  - Solid-tumor metastases of the spleen are rare and usually associated with
      disseminated disease. There are only seven reports in literature of isolated
      splenic metastases from colorectal carcinoma, which generally metastasize to
      regional lymphonodes, liver and abdominal peritoneum. We report a case of
      isolated splenic metastasis in a 55-year-old woman who had undergone left
      hemicolectomy, lymphadenectomy and chemotherapy 18 months earlier for
      adenocarcinoma of the sigmoid colon with positive pericolic and inter-aortocaval
      lymphonodes. This is the eighth documented case of isolated splenic metastasis
      from colon cancer. Previously reported cases of this type are reviewed along with
      the mechanism underlying neoplastic spread to the spleen.

PMID- 15149164
TI  - A case report of osteochondroma of the frontotemporosphenoidal suture.
AB  - Osteochondroma, also known as osteocartilaginous exostosis, is the most frequent
      benign bone tumour of the skeletal system. Despite its preference for long bones
      (tibia and femur), osteochondroma may occur in some short bones developing
      endochondral ossification. Seventy-five percent of the patients present only with
      a single lesion, whereas 25% have multiple lesions; this last clinical condition,
      defined as osteochondromatosis (disorder of autosomal dominant inheritance) shows
      a high risk of malignant transformation (about 11%). In the craniofacial area
      this tumour is very rare. The sites of predilection are the coronoid process and
      mandibular condyle, even though osteochondromas arising from the base of the
      skull, maxillary sinus and zygomatic arch have been previously described.
      However, an osteochondroma originating from the frontotemporosphenoidal suture
      has not been reported before in the literature. We present a unique case of
      osteochondroma of the frontotemporosphenoidal suture. Moreover, the relevant
      international literature has been reviewed and all diagnostic and surgical
      matters have been discussed.

PMID- 15149165
TI  - Parotid gland cancer: a case report of a primitive adenocarcinoma arising from a
      multirecurrent pleomorphic adenoma.
AB  - Parotid tumours represent a wide group of tumours which are mostly localized in
      the major salivary glands. We report a case of a 69-year old female with a
      parotid tumour history who was referred to us with a prominent lump and swelling
      localized in the right parotid area. In the period between 1985-2002, she was
      operated 5 times elsewhere for a recurrent pleomorphic adenoma of the right
      parotid (mixed tumour until 1991), which was histologically confirmed. Sixteen
      years after the primitive tumour, she underwent mastectomy and axillary
      dissection for a ductal carcinoma. Routine follow-up has been conducted on both
      malignancies. Pleomorphic adenoma is the most frequent tumour of the parotid. The
      potential risk of a malignant transformation can increase over the years with an
      incidence of 1% to 7%. Management of these recurrences is complex and
      controversial because of the different treatment options advocated such as
      radical resection with possible facial nerve sacrifice, or postoperative
      radiotherapy in non radical cases.

PMID- 15149166
TI  - Time course of urinary neopterin in a non-Hodgkin's lymphoma patient during
      chemotherapy and radiotherapy.
AB  - The objective of this study was to follow urinary neopterin in a patient affected
      by non-Hodgkin's lymphoma during the three months treatment from the onset of the
      disease. In the study a patient affected by non-Hodgkin's lymphoma in Stage IV
      (centrocyto-centroblastic type) was enrolled. He was treated with combined
      chemotherapy and local radiotherapy. Neopterin was measured by high performance
      liquid chromatography in the first morning urine specimens. The time course of
      urinary neopterin levels ranged from 110 to 524 micromol x mol(-1) creatinine
      (mean 261, SD 67.5 micromol x mol(-1) creatinine). Over 70 % of the received
      values were higher than the upper limit of normal excretion of healthy subjects.
      Longitudinal analysis showed a relatively big variance of urinary neopterin with
      a tendency of decrease during the treatment. The significant decrease of urinary
      neopterin was observed till after the radiotherapy period which followed the
      chemotherapy period. In conclusions, the response to the therapy was accompanied
      by a reversal tendency of neopterin excretion to physiological values. This study
      confirms neopterin as a suitable additional parameter for the control of non
      Hodgkin's lymphoma therapy.

PMID- 15149167
TI  - Complete nodal staging in male breast cancer. (Biopsy of axillary and internal
      mammary sentinel node).
AB  - Carcinoma of the male breast is an uncommon phenomenon, accounting for < 1% of
      all malignancies in men. Searching for a more conservative treatment we
      introduced in our clinical practice axillary sentinel node biopsy and, if
      present, sentinel node biopsy of the internal mammary chain. The potential
      clinical implications of complete nodal staging are far-reaching, and give us a
      major new opportunity to stratify male patients with breast cancer for
      appropriate surgery as well as giving valuable prognostic information.

PMID- 15149168
TI  - Ex vivo detectable activation of Melan-A-specific T cells correlating with
      inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.
AB  - The purpose of this study was to test melanoma vaccines consisting of peptides
      and immunological adjuvants for optimal immunogenicity and to evaluate laboratory
      immune monitoring for in vivo relevance. Forty-nine HLA-A2 positive patients with
      Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide, with
      or without immune adjuvant AS02B (QS21 and MPL) or IFA. Peptide-specific CD8 T
      cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers
      and IFN-gamma ELISPOT assays. The vaccines were well tolerated. In vivo expansion
      of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after
      vaccination with peptide in AS02B and 12/17 after vaccination with peptide in
      IFA). The T cells produced IFN-gamma and downregulated CD45RA and CD28. T-cell
      responses correlated with inflammatory skin reactions at vaccine injection sites
      (P < 0.001) and with DTH reaction to Melan-A peptide (P < 0.01). Twenty-six of 32
      evaluable patients showed progressive disease, whereas 4 patients had stable
      disease. The two patients with the strongest Melan-A-specific T-cell responses
      experienced regression of metastases in skin, lymph nodes, and lung. We conclude
      that repeated vaccination with Melan-A peptide in IFA frequently leads to
      sustained responses of specific CD8 T cells that are detectable ex vivo and
      correlate with inflammatory skin reactions.

PMID- 15149169
TI  - Native chemical ligation of hydrophobic [corrected] peptides in lipid bilayer
      systems.
AB  - The covalent modification of water-insoluble membrane polypeptides incorporated
      into lipid bilayers by native chemical ligation is described. The key feature of
      this strategy is the use of cubic lipidic phase (CLP) matrixes as reaction media.
      The CLP-matrix consists of a lipid bilayer into which hydrophobic polypeptides
      and folded membrane proteins can be inserted and two unbounded aqueous channels
      that give the aqueous phase access to both sides of an infinite lipid bilayer and
      thus ensure that modification of solvent-exposed sites is independent of the
      topology of membrane incorporation. The enzymatic removal of an N-terminal
      proteolytic cleavage sequence from the membrane polypeptide exposes an N-terminal
      cysteine residue. Subsequently, a C-terminal thioester peptide is joined to the N
      terminus of the polypeptide by a native chemical ligation reaction. By use of
      this approach, incorporation of a variety of molecular tools, such as
      spectroscopic probes, unnatural amino acids, and molecular markers into membrane
      proteins that cannot be easily solubilized in detergent or denaturant solutions,
      may be achieved.

PMID- 15149170
TI  - Core-cross-linked polymeric micelles as paclitaxel carriers.
AB  - Cross-linkable di- and triblock copolymers of poly(epsilon-caprolactone) (PCL)
      and monomethoxyl poly(ethylene glycol) (MPEG) were synthesized. These amphiphilic
      copolymers self-assembled into nanoscale micelles capable of encapsulating
      hydrophobic paclitaxel in their hydrophobic cores in aqueous solutions. To
      further enhance their thermodynamic stability, the micelles were cross-linked by
      radical polymerization of the double bonds introduced into the PCL blocks.
      Reaction conditions were found to significantly affect both the cross-linking
      efficiency and the micelle size. The encapsulation of paclitaxel into the
      micelles was confirmed by the proton nuclear magnetic resonance (1H NMR)
      spectroscopy. Encouragingly, paclitaxel-loading efficiency of micelles was
      enhanced significantly upon micelle core-cross-linking. Both the micelle size and
      the drug loading efficiency increased markedly with increasing the PCL block
      lengths, no matter if the micelles were core-cross-linked or not. However,
      paclitaxel-loading did not obviously affect the micelle size or size
      distribution. The cross-linked micelles exhibited a significantly enhanced
      thermodynamic stability against dilution with aqueous solvents. The efficient
      cellular uptake of paclitaxel loaded in the nanomicelles was demonstrated by
      confocal laser scanning microscopy (CLSM) imaging. This new biodegradable
      nanoscale carrier system merits further investigations for parenteral drug
      delivery.

PMID- 15149171
TI  - NMR studies of fully modified locked nucleic acid (LNA) hybrids: solution
      structure of an LNA:RNA hybrid and characterization of an LNA:DNA hybrid.
AB  - LNA is a bicyclic nucleic acid analogue that contains one or more 2'-O,4'-C
      methylene linkage(s), which effectively locks the furanose ring in a C3'-endo
      conformation. We report here the NMR solution structure of a nonamer LNA:RNA
      hybrid and a structural characterization of a nonamer LNA:DNA hybrid, where the
      LNA strands are composed entirely of LNA nucleotides. This is the first
      structural characterization of fully modified LNA oligonucleotides. The high
      resolution structure reveals that the LNA:RNA hybrid adopts an almost canonical A
      type duplex morphology. The helix axis is almost straight and the duplex geometry
      is regular. This shows that fully modified LNA oligomers can hybridize with
      complementary RNA and form duplexes within the Watson-Crick framework. The
      LNA:DNA hybrid structurally resembles an RNA:DNA hybrid as shown by determination
      of deoxyribose sugar puckers and analysis of NOESY NMR spectra.

PMID- 15149172
TI  - Antigenicity of recombinant proteins after regioselective immobilization onto
      polyanhydride-based copolymers.
AB  - We previously demonstrated that the introduction of a tag consisting of several
      contiguous lysines at the N- or C-terminus of a recombinant protein greatly
      improved the covalent grafting of the protein onto negatively charged maleic
      anhydride-alt-methyl vinyl ether (MAMVE) copolymer, under many different
      experimental conditions (Ladaviere, C., et al. (1998) Bioconjugate Chem. 9, 655;
      Allard, L., et al. (2002) Biotechnol. Bioeng. 80, 341). The grafting efficiency
      was dependent on the charge and amine density of the tag, characteristics which
      were determined by the tag composition. The six lysine tag (Lys6) was found to be
      the most efficient (Allard, L., et al. (2001) Bioconjugate Chem. 12, 972). In the
      present work, the biological activity of Lys6-proteins covalently bound to
      polymer was investigated. N- or C-terminal Lys6-tagged HIV-1 p24 recombinant
      proteins (RK24H and RH24K) were grafted onto MAMVE, and the antigenicity each of
      the bioconjugates was evaluated using six monoclonal antibodies that recognized
      different epitopes distributed along the protein. We demonstrate that the
      position of the tag and the hydrolysis rate of the anhydride moieties of the
      polymer are the two main parameters involved in the conservation of the
      biological activity of the immobilized protein. We thus present a process which
      allows an efficient oriented immobilization of proteins onto copolymers with
      optimal biological activity that is suitable for the controlled production of
      active bioconjugates.

PMID- 15149173
TI  - Cross-linked microparticles as carriers for the delivery of plasmid DNA for
      vaccine development.
AB  - Plasmid DNA was directly encapsulated into biocompatible polymer microparticles
      via radical polymerization in an inverse emulsion system. Acrylamide-based
      microspheres 0.2-1 microm in diameter were prepared using an acid-cleavable
      difunctional monomer. Retention of the DNA payload at physiological pH with
      complete release under acidic conditions at lysosomal pH was demonstrated. By
      trapping the plasmid DNA within the cross-linked microparticle, enzymatic
      degradation was prevented when exposed to serum nucleases. For vaccine
      development, these delivery vehicles were also investigated for their ability to
      generate immune responses when delivered to phagocytic cells of the immune
      system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in
      macrophages, leading to cytokine secretion of IL-6 with a response approximately
      40-fold higher than that achieved with DNA alone.

PMID- 15149174
TI  - Arginine carrier peptide bearing Ni(II) chelator to promote cellular uptake of
      histidine-tagged proteins.
AB  - Arginine-rich peptide-mediated protein delivery into living cells is a novel
      technology for controlling cell functions with therapeutic potential. In this
      report, a novel approach for the intracellular delivery of histidine-tagged
      proteins was introduced where a Ni(II) chelate of octaarginine peptide bearing
      nitrilotriacetic acid [R8-NTA-Ni(II)] was used as a membrane-permeable carrier
      molecule. Significant internalization of histidine-tagged enhanced green
      fluorescent protein (EGFP) into HeLa cells was observed by confocal microscopic
      observation in the presence of R8-NTA-Ni(II). Nuclear condensation characteristic
      in apoptotic cell death was also induced in the cells treated with a histidine
      tagged apoptosis-inducing peptide [pro-apoptotic domain peptide (PAD)],
      indicating that the cargo molecules really went through the membrane to reach the
      cytosol. The apoptosis-inducing activity of the peptide thus delivered was
      compared with that of the PAD peptide covalently connected with the octaarginine
      peptide.

PMID- 15149175
TI  - Cellular trajectories of peptide-modified gold particle complexes: comparison of
      nuclear localization signals and peptide transduction domains.
AB  - Gold nanoparticles modified with nuclear localization peptides were synthesized
      and evaluated for their subcellular distribution in HeLa human cervical
      epithelium cells, 3T3/NIH murine fibroblastoma cells, and HepG2 human
      hepatocarcinoma cells. Video-enhanced color differential interference contrast
      microscopy and transmission electron microscopy indicated that transport of
      nanoparticles into the cytoplasm and nucleus depends on peptide sequence and cell
      line. Recently, the ability of certain peptides, called protein transduction
      domains (PTDs), to transclocate cell and nuclear membranes in a receptor- and
      temperature-independent manner has been questioned (see for example, Lundberg,
      M.; Wikstrom, S.; Johansson, M. (2003) Mol. Ther. 8, 143-150). We have evaluated
      the cellular trajectory of gold nanoparticles carrying the PTD from HIV Tat
      protein. Our observations were that (1) the conjugates did not enter the nucleus
      of 3T3/NIH or HepG2 cells, and (2) cellular uptake of Tat PTD peptide-gold
      nanoparticle conjugates was temperature dependent, suggesting an endosomal
      pathway of uptake. Gold nanoparticles modified with the adenovirus nuclear
      localization signal and the integrin binding domain also entered cells via an
      energy-dependent mechanism, but in contrast to the Tat PTD, these signals
      triggered nuclear uptake of nanoparticles in HeLa and HepG2 cell lines.

PMID- 15149176
TI  - Peptidyl linkers for protein heterodimerization catalyzed by microbial
      transglutaminase.
AB  - Specific peptidyl linkers that result in the heterodimerization of functional
      proteins, which is catalyzed by microbial transglutaminase from Streptomyces
      mobaraensis (MTG), were generated based on a ribonuclease S-peptide using site
      directed mutagenesis. The peptidyl linkers designated as Lys-tag and Gln-tag were
      designed to possess sole reactive Lys or Gln residue that was amenable for
      selective Lys-Gln cross-linkage of different proteins. Green fluorescent protein
      variants, ECFP and EYFP, were employed as model proteins, and those Lys- and Gln
      tags were fused to the N-termini of ECFP and EYFP, respectively. As a result, we
      succeeded in solely obtaining the ECFP-EYFP heterodimer without forming multiply
      cross-linked byproducts. It was found that the reactivity of peptidyl linkers
      varied according to the type of amino acid to be replaced. Peptidyl linkers with
      a basic amino acid (Arg) exhibited the highest reactivity in the cross-linking
      reaction, suggesting the cationic residue substrate preference of MTG. Kinetic
      analysis utilizing fluorescent resonance energy transfer (FRET), that is only
      observed upon the heterodimeric ECFP-EYFP conjugation, revealed that the amino
      acid replacement contributed to the acceleration of cross-linking reactions by
      increasing catalytic turnover (k(cat)), rather than substrate binding affinity
      (K(m)). Finally, using a ribonuclease S-protein, the manipulation of enzymatic
      protein cross-linking based on specific S-peptide:S-protein interactions was
      explored. Since newly designed Lys- and Gln-tags retained binding affinities to
      the S-protein, the heterodimerization was perfectly restrained by wrapping them
      with the S-protein. The results suggest the possibility of limited protein
      conjugation by tuning steric hindrance against the MTG. Tailoring enzymatic
      posttranslational modifications with either engineering peptidyl substrates or by
      taking specific peptide-protein interactions into consideration may facilitate
      the development of a new sequential protein conjugation method for the
      preparation of multifunctional protein.

PMID- 15149177
TI  - 3'-methylphosphonate-modified oligo-2'-O-methylribonucleotides and their Tat
      peptide conjugates: uptake and stability in mouse fibroblasts in culture.
AB  - Antisense oligo-2'-O-methylribonucleotides and their methylphosphonate
      derivatives show high binding affinities for their complementary targets under
      essentially physiological conditions. Additionally, the methylphosphonate linkage
      is resistant to nuclease hydrolysis. Here we show that a single methylphosphonate
      internucleotide linkage at the 3'-end of an oligo-2'-O-methylribonucleotide is
      sufficient to prevent degradation by the 3'-exonuclease activity found in
      mammalian serum. Complexes formed between a cationic lipid, Oligofectamine, and
      5'-[(32)P]-labeled methylphosphonate modified oligo-2'-O-methylribonucleotides
      are taken up by mouse L(929) fibroblasts in culture. The extent of uptake appears
      to be dependent upon the sequence of the oligonucleotide. Examination of lysates
      of oligonucleotide treated cells by polyacrylamide gel electrophoresis showed
      that no degradation of the oligonucleotide occurred, even after incubation for 24
      h. A fluorescein-derivatized oligomer was shown to localize mainly in the cell
      nucleus as monitored by fluorescence microscopy. Covalent conjugates of
      fluorescein-derivatized 3'-methylphosphonate modified oligo-2'-O
      methylribonucleotides with Tat peptide, a cell permeating peptide, were also
      prepared. The Tat peptide was coupled to the 5'-end of the oligonucleotide using
      either disulfide coupling chemistry or conjugation of a keto derivative of the
      Tat peptide via a 4-(2-aminooxyethoxy-2-(ethylureido)quinoline group at the 5'
      end of the oligonucleotide. Although formation of the Tat peptide conjugates was
      confirmed by mass spectrometry, the propensity of these oligonucleotides to form
      aggregates and their apparent high affinity for plastic and glass made the
      conjugates unsuitable for studies of uptake by cells in culture.

PMID- 15149178
TI  - Cationic oxyethylene lipids. Synthesis, aggregation, and transfection properties.
AB  - Four cationic lipids (1-4) with oligo-oxyethylene units at the linkage region
      between the pseudoglyceryl backbone and the hydrocarbon chains have been
      synthesized. Two of these lipids (1 and 2) have an equal number of
      (CH(2)CH(2)O)(n)() units attached to both C-1 and C-2 positions of the
      pseudoglyceryl backbone, making their linkage regions similar, while the other
      two (3 and 4) are unsymmetrical in terms of the number of oxyethylene units in
      the linkage. Synthesis of lipids 1 and 2 involved the coupling of benzyl glycerol
      with the corresponding tosylates as a key step. Each of these lipids formed
      membranous aggregates when dispersed in water and exhibited clear thermotropic
      phase transitions typical of vesicular assemblies. The lipids 1-4 exhibited
      enhanced biological activities as gene transfer agents compared to their non
      oxyethylene diether analogue, DHTMA. Transfection experiments using aqueous
      suspensions of these lipids and also their mixtures with cholesterol or dioleoyl
      phosphatidyl ethanolamine (DOPE) were performed on HeLa cells. The best
      transfection activity was demonstrated by unsymmetrical lipid 3, which had two
      oxyethylene units only at the C-1 position of the pseudoglycerylbackbone.

PMID- 15149179
TI  - Efficient conjugation and characterization of distamycin-based peptides with
      selected oligonucleotide stretches.
AB  - Selected sequences of oligodeoxyribonucleotides (ODNs) have been conjugated
      efficiently with distamycin-based peptides containing reactive cysteine and
      oxyamine functionalities at the C-terminus. The conjugation was performed easily
      within 30-60 min, using individual modified oligonucleotide stretches having
      sequences of 5'-d(GCTTTTTTCG)-3', 5'-d(GCTATATACG)-3', and 5'-AGCGCGCGCA-3'. Two
      types of linkages were used for making the covalent connection: (i) a five
      membered thiazolidine ring and (ii) an oxime. These distamycin-like polyamide-ODN
      conjugates were then converted to the corresponding DNA duplexes using
      complementary oligonucleotide sequences. To elucidate the binding specificity of
      the distamycin-oligonucleotide conjugates, UV-melting temperature measurements
      were performed. These studies indicated that the distamycin-ODN conjugate favored
      binding with the duplex with sequence 5'-d(GCTTTTTTCG)-3' rather than 5'
      d(GCTATATACG)-3'. On the other hand, no stabilization of the duplex with sequence
      5'-d(AGCGCGCGCA)-3' was observed. UV results also suggest that the thiazolidine
      and oxime linkages do not significantly influence the process of distamycin
      binding to the minor groove surface of the DNA duplex. The results obtained from
      duplex UV-melting studies were further corroborated by a temperature-dependent
      study of the circular dichroism spectra of the conjugates and a fluorescence
      displacement titration assay using Hoechst 33258 fluorophore as a competitive
      binder for the minor groove. All these studies reinforce the fact that the
      specific stabilization of A/T rich DNA-DNA duplexes by distamycin was preserved
      upon conjugation with oligonucleotide stretches.

PMID- 15149180
TI  - Promotion of peptide antimicrobial activity by fatty acid conjugation.
AB  - Three peptides, YGAA[KKAAKAA](2) (AKK), KLFKRHLKWKII (SC4), and YG[AKAKAAKA](2)
      (KAK), were conjugated with lauric acid and tested for the effect on their
      structure, antibacterial activity, and eukaryotic cell toxicity. The conjugated
      AKK and SC4 peptides showed increased antimicrobial activity relative to
      unconjugated peptides, but the conjugated KAK peptide did not. The circular
      dichroism spectrum of AKK showed a significantly larger increase in its alpha
      helical content in the conjugated form than peptide KAK in a solution containing
      phosphatidylethanolamine/phosphotidylglycerol vesicles, which mimics bacterial
      membranes. The KAK and AKK peptides and their corresponding fatty acid conjugates
      showed little change in their structure in the presence of phosphatidylcholine
      vesicles, which mimic the cell membrane of eukaryotic cells. The hemolytic
      activity of the KAK and AKK peptides and conjugates was low. However, the SC4
      fatty acid conjugate showed a large increase in hemolytic activity and a
      corresponding increase in helical content in the presence of phosphatidylcholine
      vesicles. These results support the model of antimicrobial peptide hemolytic and
      antimicrobial activity being linked to changes in secondary structure as the
      peptides interact with lipid membranes. Fatty acid conjugation may improve the
      usefulness of peptides as antimicrobial agents by enhancing their ability to form
      secondary structures upon interacting with the bacterial membranes.

PMID- 15149181
TI  - Design, synthesis, and evaluation of 5'-S-aminoethyl-N(6)- azidobenzyl-5'
      thioadenosine biotin conjugate: a bifunctional photoaffinity probe for the es
      nucleoside transporter.
AB  - A bifunctional biotinylated photoaffinity label for the nitrobenzylmercaptopurine
      riboside (NBMPR)-sensitive (es) nucleoside transporter (ENT1) has been
      synthesized and evaluated. This new probe,5'-S-aminoethyladenosine-N(6)
      azidobenzyl-5'-thioadenosine biotin conjugate (SAEATA-14-biotin), exhibited high
      affinity binding to the es transporter in K562 cells as determined by flow
      cytometry, with a K(i) of 2.69 nM in competition against 5-(SAENTA)-x8
      fluorescein. It also exhibited covalent linking to the es transporter in BeWo
      cell membranes upon UV irradiation. This new bifunctional probe is a potential
      tool for determining the amino acid residues involved in ligand binding at the
      NBMPR-binding site of the ENT1 nucleoside transporter, as well as for the
      purification of the transporter.

PMID- 15149182
TI  - Synthesis of thiol-reactive lipopeptide adjuvants. Incorporation into liposomes
      and study of their mitogenic effect on mouse splenocytes.
AB  - Synthetic analogues of triacylated and diacylated lipopeptides derived from the N
      terminal domain of respectively bacterial and mycoplasmal lipoproteins are highly
      potent immunoadjuvants when administered either in combination with protein
      antigens or covalently linked to small peptide epitopes. Because of their
      amphipathic properties, lipopeptides, such as S-[2,3-bis(palmitoyloxy)-(2RS)
      propyl]-N-palmitoyl-(R)-cysteinyl-alanyl-glycine (Pam(3)CAG), can be conveniently
      incorporated into liposomes and serve as anchors for antigens that are linked to
      them. To design vaccination constructs based on synthetic peptides and liposomes
      as vectors. we have accordingly synthesized a series of lipopeptides that differ
      by the number (Pam(3)C vs Pam(2)C) and nature of the acyl chains (palmitoyl vs
      oleoyl) and by the presence at their C-terminus of thiol-reactive functions, such
      as maleimide or bromoacetyl. When incorporated into liposomes, these latter
      functionalized lipopeptides allow, in aqueous media, a well controlled
      chemoselective conjugation of HS-peptides to the surface of the vesicles. Using a
      BALB/c mice splenocyte proliferation assay ([(3)H]thymidine incorporation), we
      have measured the lymphocyte activation potency of the different lipopeptides. We
      found that, compared to their free (emulsified) forms, the liposomal lipopeptides
      were endowed with enhanced mitogenic activities; i.e., up to 2 orders of
      magnitude for Pam(3)CAG which was more potent than Pam(2)CAG. The impact of
      functionalization on the cellular activity of Pam(3)CAG was dependent on the
      thiol-reactive group introduced: whereas the bromoacetyl derivative retained its
      full activity, the presence of a maleimide group virtually abolished the
      lymphocyte activation of the lipopeptide. Finally, the substitution of saturated
      palmitoyl chains by unsaturated oleoyl chains was inhibitory. Thus, thiol
      reactive Ol(3)CAG derivatives were the least active mitogens in our assay. Taken
      together, our findings are of importance for the further optimization of antigen
      specific liposomal-based synthetic vaccines; the bromoacetyl derivative of
      Pam(3)CAG should be a promising lipopeptide derivative serving as an anchor for
      peptide epitopes while retaining its lymphocyte activation activity.

PMID- 15149183
TI  - Microwave-supported preparation of (68)Ga bioconjugates with high specific
      radioactivity.
AB  - The generator-produced positron-emitting (68)Ga (T(1/2) = 68 min) is of potential
      interest for clinical PET. (68)Ga as a metallic cation is suitable for
      complexation reactions with chelators, naked or conjugated, with peptides or
      other macromolecules. Large (68)Ga generator eluate volumes, metal traces from
      the generator column material, or reaction reagents, however, disturb a fast,
      reliable, and quantitative labeling procedure. In this paper we describe a simple
      technique, based on anion exchange, aiming first, to increase the (68)Ga
      concentration, second to purify it from competing impurities, and third to obtain
      a fast and quantitative (68)Ga-labeled peptide conjugate that can be applied in
      humans without further purification. Within 5 min one can obtain from the
      original 6 mL generator eluate a 200 microL (68)Ga preparation (volume reduction
      by a factor 30) that is suitable for direct and quantitative labeling of peptide
      conjugates. DOTATOC (DOTA-D-Phe(1)-Tyr(3)-octreotide, DOTA = 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid) was used as a test tracer for
      comparing the labeling properties of the different (68)Ga preparations. In
      combination with microwave heating, peptide conjugates of 0.5-1 nmol quantities
      could be labeled within 10 min with the full (68)Ga activity of a generator.
      Further purification of the (68)Ga-labeled peptide conjugate was no longer
      required since the nuclide incorporation was quantitative. The specific
      radioactivity (with respect to the peptide) was improved by a factor
      approximately 100 compared to the previously applied techniques using the
      original generator eluate. The commercial (68)Ge/(68)Ga generator from Obninsk in
      combination with this system for purification and concentration with an
      integrated microwave-supported labeling technology resulted in a kitlike
      technology for (68)Ga-tracer production. The first automated prototype using this
      technology is being tested.

PMID- 15149184
TI  - Two technetium-99m-labeled cholecystokinin-8 (CCK8) peptides for scintigraphic
      imaging of CCK receptors.
AB  - A broad spectrum of radiolabeled peptides with high affinity for receptors
      expressed on tumor cells is currently under preclinical and clinical
      investigation for scintigraphic imaging and radionuclide therapy. The present
      paper evaluates two (99m)Tc-labeled forms of the C-terminal octapeptide of
      cholecystokinin (CCK8): sulfated (s)CCK8, with high affinity for CCK1 and CCK2
      receptors, and nonsulfated (ns)CCK8, with high affinity for CCK2 receptors but
      low affinity for CCK1 receptors. Peptides were conjugated with the bifunctional
      chelator N-hydroxysuccinimidyl hydrazino niconitate (s-HYNIC). (99m)Tc-labeling,
      performed in the presence of nicotinic acid and tricine, was highly efficient
      (approximately 95%) and yielded products with a high specific activity
      (approximately 700 Ci/mmol) and good stability (approximately 5% release of
      radiolabel during 16 h incubation in phosphate buffered saline at 37 degrees C).
      Chinese hamster ovary cells stably expressing the CCK1 receptor (CHO-CCK1 cells)
      internalized approximately 3% of added (99m)Tc-sCCK8 per confluent well during 2
      h at 37 degrees C. Internalization was effectively blocked by excess unlabeled
      sCCK8. CHO-CCK1 cells did not internalize (99m)Tc-nsCCK8. Displacement of (99m)Tc
      sCCK8 and -nsCCK8 by unlabeled CCK-8 (performed at 0 degrees C to prevent
      internalization) revealed 50% inhibitory concentrations (IC(50)) of 8 nM and >1
      microM, respectively. CHO-CCK2 cells internalized approximately 25% and
      approximately 5% of added (99m)Tc-sCCK8 and -nsCCK8, respectively. In both cases
      internalization was blocked by excess unlabeled peptide. IC(50) values for the
      displacement of (99m)Tc-sCCK8 and -nsCCK8 were 3 nM and 10 nM, respectively. CHO
      CCK1 cell-derived tumors present in one flank of athymic mice accumulated 2.0% of
      injected (99m)Tc-sCCK8 per gram tissue at 1 h postinjection. This value decreased
      to 0.6% following coinjection with excess unlabeled peptide. Uptake of (99m)Tc
      nsCCK8 was low (0.2%) and not did change by excess unlabeled peptide (0.3%).
      Accumulation of (99m)Tc-sCCK8 and -nsCCK8 by CHO-CCK2 cell-derived tumors
      (present in the other flank) amounted to 4.2% and 0.6%, respectively. In both
      cases uptake was significantly reduced by excess unlabeled peptide to 1.0% and
      0.4% for sCCK8 and nsCCK8, respectively. Accumulation of (99m)Tc-sCCK8 was also
      high in pancreas (11.7%), stomach (2.0%), and kidney (2.1%), whereas uptake of
      (99m)Tc-nsCCK8 was high in stomach (0.7%) and kidney (1.4%). Both radiolabeled
      peptides showed a rapid blood clearance. In conclusion, these data show that CCK8
      analogues can be efficiently labeled with (99m)Tc using s-HYNIC as chelator and
      nicotinic acid/tricine as coligand system without compromising receptor binding.
      Furthermore, the present study demonstrates that CCK1 tumors hardly accumulate
      (99m)Tc-nsCCK8, CCK2 tumors accumulate 2 times more (99m)Tc-sCCK8 than CCK1
      tumors, and CCK2 tumors accumulate 15 times more (99m)Tc-sCCK8 than (99m)Tc
      nsCCK8. Although accumulation in some nontarget organs was also higher with
      (99m)Tc-sCCK8, this may not reflect the human situation due to a different
      receptor expression pattern in humans as compared to mice. Therefore, further
      studies are warranted to investigate the possible use of (99m)Tc-sCCK8 for
      scintigraphic imaging of CCK receptor-positive tumors in humans.

PMID- 15149185
TI  - Methoxyoxalamido chemistry in the synthesis of novel amino linker and spacer
      phosphoramidites: a robust means for stability, structural versatility, and
      optimal tether length.
AB  - We have developed a general route to the synthesis of novel amino linker and
      spacer phosphoramidites utilizing methoxyoxalamido (MOX) chemistry. The synthesis
      makes use of readily available and inexpensive primary aliphatic amino alcohols
      and diamines to produce a rich and diverse variety of phosphoramidites. Among
      these are monomers with exceptionally long (up to 56 atoms in length) amphipathic
      tethering arms. The chemistry bestows exceptional control over the physical
      characteristics within the tethers through the selection of appropriate building
      blocks. Furthermore, MOX chemistry enables fairly rapid assembly of these
      discrete-length tethers in a modular fashion. All novel phosphoramidites were
      successfully used in automated syntheses of 5'-modified oligonucleotides.

PMID- 15149186
TI  - Synthesis and in vitro evaluation of PNA-peptide-DETA conjugates as potential
      cell penetrating artificial ribonucleases.
AB  - We report the synthesis of novel artificial ribonucleases with potentially
      improved cellular uptake. The design of trifunctional conjugates 1a and 1b is
      based on the specific RNA-recognizing properties of PNA, the RNA-cleaving
      abilities of diethylenetriamine (DETA), and the peptide (KFF)(3)K for potential
      uptake into E. coli. The conjugates were assembled in a convergent synthetic
      route involving native chemical ligation of a PNA, containing an N-terminal
      cysteine, with the C-terminal thioester of the cell-penetrating (KFF)(3)K peptide
      to give 12a and 12b. These hybrids contained a free cysteine side-chain, which
      was further functionalized with an RNA-hydrolyzing diethylenetriamine (DETA)
      moiety. The trifunctional conjugates (1a, 1b) were evaluated for RNA-cleaving
      properties in vitro and showed efficient degradation of the target RNA at two
      major cleavage sites. It was also established that the cleavage efficiency
      strongly depended on the type of spacer connecting the PNA and the peptide.

PMID- 15149187
TI  - A modular approach to the synthesis of new reagents useful in the chemical
      synthesis of modified DNA probes: derivatives of 3-(tert
      butyldimethylsiloxy)glutaric anhydride as versatile building blocks in the
      synthesis of new phosphoramidites and modified solid supports.
AB  - We present a flexible and cost-efficient synthetic strategy for the preparation
      of a new family of phosphoramidite and solid-support reagents that can introduce
      a broad range of modifications into DNA probes. The key intermediate material 3
      is synthesized using the inexpensive and commercially available 3-(tert
      butyldimethylsiloxy)glutaric anhydride 1 and can be used as common starting
      material for the preparation of new labeling reagents.

PMID- 15149188
TI  - Synthesis of marimastat and a marimastat conjugate for affinity chromatography
      and surface plasmon resonance studies.
AB  - Immobilized small-molecule inhibitors are suited for enrichment of biomolecules
      by affinity chromatography, as it is shown for metalloproteinases and an
      immobilizable derivative of the hydroxamate-type inhibitor marimastat. A new
      asymmetric synthesis of marimastat is presented that allows for site-specific
      attachment to a solid surface, e.g., a chromatography matrix or a surface plasmon
      resonance sensor chip. The latter technique is shown to be a valuable tool for
      the optimization of binding and elution conditons of biomolecules in affinity
      chromatography.

PMID- 15149189
TI  - Biotin reagents in antibody pretargeting. 6. Synthesis and in vivo evaluation of
      astatinated and radioiodinated aryl- and nido-carboranyl-biotin derivatives.
AB  - An investigation has been conducted to prepare and evaluate several
      radiohalogenated biotin derivatives as part of our studies to develop reagents
      for carrying (211)At in cancer pretargeting protocols. The primary goal of the
      investigation was to determine the in vivo stability and distribution properties
      of astatinated biotin derivatives. In addition to astatination, the biotin
      derivatives were radioiodinated for in vitro and in vivo comparison.
      Biodistributions were conducted in athymic mice, with sacrifice times of 1, 4,
      and 24 h to correspond to 9%, 32%, and 90% of (211)At decay (t(1/2) = 7.21 h). In
      the investigation, two biotin derivatives, 1a and 2a, were synthesized which had
      structures that contain a biotin moiety, a biotinidase-blocking moiety, an ether
      linker moiety, and an aryl stannane moiety for radiohalogenation. Biotin
      derivatives 1a and 2a were radiolabeled with (125/131)I to give [(125)/(131)I]1b
      or [(125)I]2b and with (211)At to give [(211)At]1c or [(211)At]2c. In vivo
      studies demonstrated that co-injected [(125)I]2b and [(131)I]1b had very similar
      tissue distributions in athymic mice. Co-injection of [(211)At]2c and [(125)I]2b
      provided data that indicated that rapid deastatination occurred in vivo. A second
      set of biotin derivatives, 3a, 4a, and 5a, were synthesized which had structures
      that contain a biotin moiety, a biotinidase-blocking moiety, and an anionic nido
      carborane moiety for radiohalogenation. The biotin derivatives 4a and 5a
      contained an aryl moiety not present in 3a, and 5a had a trialkylamine
      functionality not present in 3a or 4a. Biotin derivative 3a was radioiodinated,
      but was not further investigated. Biotin derivatives 4a and 5a were radiolabeled
      with (211)At and (125)I to produce [(125)I]4b/[(211)At]4c and
      [(125)I]5b/[(211)At]5c. Comparison of [(125)I]4b and (separately) [(125)I]5b with
      [(131)I]1b showed that the nido-carborane containing biotin derivatives were
      retained in blood and tissue more than the aryl iodide derivative. In vivo
      evaluations of [(211)At]4c/[(125)I]4b and (separately) [(211)At]5c/[(125)I]5b
      indicated that some deastatination occurred in these compounds, but it was much
      less than observed for the aryl derivative [(211)At]2c. While the nido-carborane
      containing biotin derivatives provide a significant improvement in astatine
      stability over biotin derivatives previously studied, additional derivatives need
      to be prepared and studied to further improve the in vivo stability and
      blood/tissue clearance of these compounds.

PMID- 15149190
TI  - Design and synthesis of a new [18F]fluoropyridine-based haloacetamide reagent for
      the labeling of oligonucleotides: 2-bromo-N-[3-(2-[18F]fluoropyridin-3
      yloxy)propyl]acetamide.
AB  - Based on the recently highlighted potential of nucleophilic heteroaromatic ortho
      radiofluorinations in the preparation of fluorine-18-labeled radiotracers and
      radiopharmaceuticals for PET, a [(18)F]fluoropyridine-based bromoacetamide
      reagent has been prepared and used in prosthetic group introduction for the
      labeling of oligonucleotides. [(18)F]FPyBrA (2-bromo-N-[3-(2-[(18)F]fluoropyridin
      3-yloxy)propyl]acetamide) was designed as a radiochemically feasible reagent, its
      pyridinyl moiety both carrying the radioactive halogen (fluorine-18) and allowing
      its efficient incorporation via a nucleophilic heteroaromatic substitution, and
      its 2-bromoacetamide function, ensuring the efficient alkylation of a
      phosphorothioate monoester group born at the 3'- or 5'-end of single-stranded
      oligonucleotides. [(18)F]FPyBrA (HPLC-purified) was efficiently prepared in 18
      20% non-decay-corrected yield (based on starting [(18)F]fluoride) using a three
      step radiochemical pathway in 80-85 min. The developed procedure involves (1) a
      high-yield nucleophilic heteroaromatic ortho-radiofluorination as the fluorine-18
      incorporation-step (70-85% radiochemical yield) and uses [3-(3-tert
      butoxycarbonylaminopropoxy)pyridin-2-yl]trimethylammonium
      trifluoromethanesulfonate as precursor for labeling, followed by (2) rapid and
      quantitative TFA-removal of the N-Boc-protective group and (3) condensation with
      2-bromoacetyl bromide (45-65% radiochemical yield). Typically, 3.3-3.7 GBq (90
      100 mCi) of HPLC-purified [(18)F]FPyBrA could be obtained in 80-85 min, starting
      from 18.5 GBq (500 mCi) of a cyclotron production batch of [(18)F]fluoride.
      [(18)F]FPyBrA was regioselectively conjugated with 9-mer and 18-mer single
      stranded oligonucleotides, provided with a phosphorothioate monoester group at
      their 3'-end. Both natural phosphodiester DNAs and in vivo-stable 2'-methoxy and 
      fluoro-modified RNAs were used. Conjugation uses optimized, short-time reaction
      conditions (MeOH/0.1 M PBS pH 7.4, 15 min, 120 degrees C), both compatible with
      the chemical stability of the oligonucleotides (ONs) and the half-life of
      fluorine-18. Conjugated [(18)F]ONs were finally purified by RP-HPLC and desalted
      using a Sephadex NAP-10 column. The whole radiosynthetic procedure, including the
      preparation of the fluorine-18-labeled reagent, the conjugation with the
      oligonucleotide, and the HPLC purification and formulation lasted 140-160 min.
      [(18)F]FPyBrA represents a valuable alternative to the already reported N-(4
      [(18)F]fluorobenzyl)-2-bromoacetamide for the design and development of
      oligonucleotide-based radiopharmaceuticals for PET.

PMID- 15149191
TI  - Synthesis, characterization, and biological evaluation of neutral nitrido
      technetium(V) mixed ligand complexes containing dithiolates and
      aminodiphosphines. A novel system for linking technetium to biomolecules.
AB  - A new biomolecule labeling method that utilizes the [(99m)Tc(N)(PNP)](2+) metal
      fragment is presented. Thus, a series of nitrido mixed-ligand M(V) complexes (M =
      (99m)Tc, (99g)Tc, Re), [M(N)(Ln)(PNP)], where Ln is the dianionic form of a
      dithiolate or substituted-dithiolate ligand and PNP is an aminodiphosphine, is
      described. (99m)Tc complexes can be prepared using either a two-step or a three
      step procedure starting from generator-eluted pertechnetate through a prereduced
      mixture of [(99m)Tc(N)]-containing species, followed by sequential or
      contemporary addition of the relevant dithiolate and aminodiphosphine. The
      reactions of 2,3-dimercaptopropionic acid (H(2)L1) with [Tc(N)(PNP)](2+) were
      investigated in detail. It was found that this bidentate ligand coordinated the
      metal fragment through the [S(-),S(-)] donor atom pair, to yield neutral mixed
      ligand complexes [(99m)Tc(N)(L1)(PNP)] in high specific activity. The additional
      carboxylic functional group was not involved in metal coordination, thus
      remaining available for conjugation to target-specific molecules. Dithiolates
      incorporating pendant functional group(s) gave rise to a 1:1 diastereoisomeric
      mixture of syn-[M(N)(Ln)(PNP)] and anti-[M(N)(Ln)(PNP)] derivatives, depending on
      the relative orientation of the dithiolate substituent(s) with respect to the
      terminal nitrido group, and no isomeric conversion was detected. (99m)Tc species
      had been proven to be identical with the (99g)Tc complexes prepared at the
      macroscopic level by comparison of the corresponding radiometric and UV/vis HPLC
      profiles. Challenge experiments with cysteine or glutathione indicated that these
      physiological agents had no effect on the stability of this class of mixed-ligand
      (99m)Tc-complexes. Biodistribution studies in rats of selected (99m)Tc-complexes
      showed a rapid clearance from the blood and tissues after 60 min pi.

PMID- 15149192
TI  - Synthesis and fluorescence studies of multiple labeled oligonucleotides
      containing dansyl fluorophore covalently attached at 2'-terminus of cytidine via
      carbamate linkage.
AB  - Synthesis of modified oligonucleotides in which the specific cytidine nucleoside
      analogues linked at 2'-OH position via a carbamate bond with an amino ethyl
      derivative of dansyl fluorophore is reported. For the multiple labeling of
      oligonucleotides, a strategy involving prelabeling at the monomeric level
      followed by solid phase assembly of oligonucleotides to obtain regiospecifically
      labeled probes has been described. The labeled monomer was phosphitylated using 2
      cyanoethyl-N,N,N',N'-tetraisopropyl-phosphoramidite (Bis-reagent) and
      pyridiniumtrifluoro acetate (Py.TFA) as an activator. To ascertain the minimal
      number of labeled monomers required for a specific length of oligonucleotide for
      detection and also to assess the effect of carbamate linkage on hybridization,
      hexamer and 20-mer sequences were selected. Both were labeled with 1, 2, and 3
      monomers at the 5'-end and hybridized with normal (unmodified) complementary
      sequences. As compared to midsequence or 3'-terminal labeling reported earlier,
      the 5'-terminal labeling has been found to have minimal contact-mediated
      quenching on duplex formation. This may be due to complementary deoxyguanosine
      (dG) rich oligonucleotide sequences or CG base pairs at a terminus that is known
      to yield stronger binding. This is one reason for selecting cytidine for
      labeling. The results may aid rational design of multiple fluorescent DNA probes
      for nonradioactive detection of nucleic acids.

PMID- 15149193
TI  - Evaluation of cleavable (Tyr3)-octreotate derivatives for longer intracellular
      probe residence.
AB  - Radioligand targeting of somatostatin receptor subtype 2 (sstr2)-positive tumors
      with synthetic somatostatin analogues such as octreotide is subject to
      improvement in tumor to nontumor biodistribution, in part because internalization
      of such somatostatin analogues is limited by sstr2 recycling to the cell surface.
      We reasoned that it might be possible to prepare probe-carrying somatostatin
      analogues that would escape recycling, efficiently depositing probe molecules
      inside cells and ultimately increasing their intracellular concentration. We have
      incorporated cathepsin-B-cleavable linkers into (Tyr3)-octreotate chelate
      conjugates and examined these constructs as to cellular uptake, externalization,
      subcellular localization, and cleavage in the rat pancreatic tumor cell line
      AR42J in culture. Comparison of the cleavable radioligands with a noncleavable
      control indicates that scission of the constituent cathepsin B substrate occurs
      at a rate faster than ligand externalization, depositing virtually all
      internalized cleaved radiochelates within lysosomal compartments.

PMID- 15149194
TI  - Direct production of proteins with N-terminal cysteine for site-specific
      conjugation.
AB  - Proteins with N-terminal cysteine can undergo native chemical ligation and are
      useful for site-specific N-terminal labeling or protein semisynthesis.
      Recombinant production of these has usually been by site-specific cleavage of a
      precursor fusion protein at an internal cysteine residue. Here we describe a
      simpler route to producing these proteins. Overexpression in E. coli of several
      proteins containing cysteine as the second amino acid residue yielded products in
      which the initiating methionine residue had been completely cleaved by endogenous
      methionine aminopeptidase. While secondary modification of the terminal cysteine
      was a complicating factor, conditions were identified to eliminate or minimize
      this problem. Recombinant proteins produced in this way were suitable for site
      specific modification of the amino terminus via native chemical ligation
      technology, as demonstrated by conjugation of a thioester-containing derivative
      of fluorescein to one such protein. The ability to directly produce proteins with
      N-terminal cysteine should simplify the application of native chemical ligation
      technology to recombinant proteins and make the technique more amenable to
      researchers with limited expertise in protein chemistry.

PMID- 15149195
TI  - An S-layer heavy chain camel antibody fusion protein for generation of a
      nanopatterned sensing layer to detect the prostate-specific antigen by surface
      plasmon resonance technology.
AB  - The bacterial cell surface layer (S-layer) protein of Bacillus sphaericus CCM
      2177 assembles into a square lattice structure and recognizes a distinct type of
      secondary cell wall polymer (SCWP) as the proper anchoring structure in the rigid
      cell wall layer. For generating a nanopatterned sensing layer with high density
      and well defined distance of the ligand on the outermost surface, an S-layer
      fusion protein incorporating the sequence of a variable domain of a heavy chain
      camel antibody directed against prostate-specific antigen (PSA) was constructed,
      produced, and recrystallized on gold chips precoated with thiolated SCWP. The S
      layer protein moiety consisted of the N-terminal part which specifically
      recognized the SCWP as binding site and the self-assembly domain. The PSA
      specific variable domain of the camel heavy chain antibody was selected by
      several rounds of panning from a phage display library of an immunized dromedary,
      and was produced by heterologous expression in Escherichia coli. For construction
      of the S-layer fusion protein, the 3'-end of the sequence encoding the C
      terminally truncated form rSbpA(31)(-)(1068) was fused via a short linker to the
      5'-end of the sequence encoding cAb-PSA-N7. The S-layer fusion protein had
      retained the ability to self-assemble into the square lattice structure.
      According to the selected fusion site in the SbpA sequence, the cAb-PSA-N7 moiety
      remained located on the outer surface of the protein lattice. After
      recrystallization of the S-layer fusion protein on gold chips precoated with
      thiolated SCWP, the monomolecular protein lattice was exploited as sensing layer
      in surface plasmon resonance biochips to detect PSA.

PMID- 15149196
TI  - Osmotic pressure control in response to a specific ion signal at physiological
      temperature using a molecular recognition ion gating membrane.
AB  - A molecular recognition gating ion membrane was prepared by graft
      copolymerization of N-isopropylacrylamide and benzo[18]crown-6-acrylamide onto
      the pore surface of porous polyethylene film. This membrane captured Ba2+ with
      its crown ether receptors and generated osmotic pressure in response to Ba2+
      autonomously and reversibly. However, the membrane never generated osmotic
      pressure in response to Ca2+. In addition, the concentration gradient of both the
      ion and other solute such as dextran could be used as the driving force; using a
      dextran concentration gradient, we can control the critical concentration and the
      duration time of the osmosis response.

PMID- 15149197
TI  - Chiral dimeric capsules from N,C-linked peptidocalix[4]arenes self-assembled
      through an antiparallel beta-sheetlike motif.
AB  - The first example of a calix[4]arene amino acid is reported. It allowed the
      synthesis of the novel N,C-linked peptidocalix[4]arenes which self-assemble in
      low-polarity media to give chiral dimeric capsules held together by an
      antiparallel beta-sheetlike hydrogen-bonding motif.

PMID- 15149199
TI  - Zn2+-dependent peptide nucleic acids probes.
AB  - Binding of bis-picolylamine-naphthalene diimide-peptide nucleic acid conjugates
      to complementary DNA is strongly dependent upon Zn2+; ultimately, hybridization
      is switched ON in the presence muM Zn2+.

PMID- 15149198
TI  - Zinc oxide quantum rods.
AB  - Nanoscale zinc oxide (ZnO) rods of diameters close to the Bohr-exciton radius (
      approximately 2 nm) can be prepared from a simple acetate precursor, resulting in
      ligand-capped rods of ZnO, highly dispersible in nonpolar solvents. Zinc oxide,
      ZnO, is a wide band-gap semiconductor with applications in blue/ultraviolet (UV)
      optoelectronic devices and piezoelectric devices. We observe self-assembly into
      uniform stacks of nanorods aligned parallel to each other with respect to the
      long axis, and photoluminescence measurements provide evidence for one
      dimensional quantum confinement.

PMID- 15149200
TI  - Formation of a highly oxidized iron biliverdin complex upon treatment of a five
      coordinate verdoheme with dioxygen.
AB  - Treatment of a green solution of the five-coordinate octaethylverdoheme,
      XFeII(OEOP) 1 (X = Cl or Br), with dioxygen results in the formation of a new
      iron complex of octaethylbiliverdin, 2, within a matter of minutes. The reaction
      has been monitored by 1H NMR spectroscopy, and the product 2 (X = Cl) has been
      isolated and examined by X-ray crystallography. The structure of 2 (X = Cl) shows
      that the iron is five-coordinate with bonds to the four nitrogen atoms of the
      helical tetrapyrrole ligand and to an axial chloride. Treatment of 2 (X = Cl or
      Br) with zinc amalgam produces the known iron(III) complex of biliverdin,
      {FeIII(OEB)}2. The unusual pattern of resonances in the 1H NMR spectrum of 2 and
      its facile reduction to {FeIII(OEB)}2 indicate that 2 is an oxidized complex that
      can be formulated by resonance structures involving either an Fe(IV) ion bound to
      a bilindione trianion or an Fe(III) ion bound to an oxidized, dianionic, radical
      form of the ligand.

PMID- 15149202
TI  - Substrate electric dipole moment exerts a pH-dependent effect on electron
      transfer in Escherichia coli photolyase.
AB  - Transient absorption spectroscopy is used to demonstrate that the electric dipole
      moment of the substrate cyclobutane thymine dimer affects the charge
      recombination reaction between fully reduced flavin adenine dinucleotide (FADH-)
      and the neutral radical tryptophan 306 (Trp306*) in Escherichia coli DNA
      photolyase. At pH 7.4, the charge recombination is slowed by a factor of 1.75 in
      the presence of substrate, but not at pH 5.4. Photolyase does bind substrate at
      pH 5.4, and it seems that this pH effect originates from the conversion of FADH-
      to FADH2 at lower pH. The free-energy changes calculated from the electric field
      parameters and from the change in electron transfer rate are in good agreement
      and support the idea that the substrate electric dipole is responsible for the
      observed change in electron transfer rate. It is expected that the substrate
      electric field will also modify the physiologically important from excited 1FADH-
      to the substrate in the DNA repair reaction.

PMID- 15149201
TI  - Building addressable libraries: the use of electrochemistry for generating
      reactive Pd(II) reagents at preselected sites on a chip.
AB  - A Pd(II) reagent has been generated at preselected sites on an electrochemically
      addressable chip. The reagent was used to effect the Wacker oxidation of an
      olefin substrate bound to the chip near the electrode. The use of ethyl vinyl
      ether in the solution above the chip effectively kept the Pd(II) reagent
      generated at the preselected electrode from migrating to neighboring electrodes
      and initiating Wacker oxidations at unwanted sites on the chip.

PMID- 15149203
TI  - Steric and magnetic asymmetry distinguished by encapsulation.
AB  - Guests in an achiral cavity experience asymmetric magnetic environments induced
      by chiral centers outside the cavity.

PMID- 15149205
TI  - Stair motifs at protein-DNA interfaces: nonadditivity of H-bond, stacking, and
      cation-pi interactions.
AB  - At the interface between protein and double-stranded DNA, stair motifs
      simultaneously involve three different types of pairwise interactions: aromatic
      base stacking, hydrogen bonding, and cation-pi. The relative importance of these
      interactions is studied in the stair motif occurring in the 1TC3 crystal
      structure, which involves an arginine and two stacked guanines, by means of
      Hartree-Fock (HF) and Moller-Plesset energy and free energy calculations,
      including vibrational, rotational, translational contributions, both in a vacuum
      and various solvents. The results obtained show an anti-cooperative tendency of
      the HF energy and vibrational free energy terms, and the cooperativity of the
      rotational, translational, and solvation free energies. Hence, the cooperativity
      of the stair motif interactions, in the context of protein-DNA recognition, can
      be viewed as arising from the environment.

PMID- 15149204
TI  - Nanomechanical control of glucopyranose rotamers.
AB  - Single molecules of beta-1 --> 6-linked d-glucose polysaccharides, when stretched
      in an atomic force microscope, display a hookean-like elasticity unusual for
      polymers. High-level ab initio calculations and microsecond-scale molecular
      dynamics simulations reveal that this elasticity is governed by force-induced
      rotations of the exocyclic group on the glucopyranose rings from their short and
      less energetic gt and gg conformations to the extended and high-energy tg state.
      These observations indicate that a simple stretching of 1 --> 6-linked glucose
      polysaccharides provide a unique means to control glucopyranose rotamer
      populations.

PMID- 15149206
TI  - A charge-transfer-induced spin transition in the discrete cyanide-bridged complex
      [[Co(tmphen)2]3[Fe(CN)6]2].
AB  - A charge-transfer-induced spin transition (CTIST) is observed in the discrete
      cyanide-bridged complex, {[Co(tmphen)2]3[Fe(CN)6]2}. Single-crystal X-ray
      diffraction, 57Fe Mossbauer spectroscopy, and magnetic susceptibility were used
      collectively to describe the oxidation states of the Co and Fe ions in this
      cluster as a function of temperature. This pentanuclear complex represents the
      first example of a CTIST at the discrete molecular level.

PMID- 15149207
TI  - Development of a quantum mechanics-based free-energy perturbation method: use in
      the calculation of relative solvation free energies.
AB  - Free-energy perturbation (FEP) is considered the most accurate computational
      method for calculating relative solvation and binding free-energy differences.
      Despite some success in applying FEP methods to both drug design and lead
      optimization, FEP calculations are rarely used in the pharmaceutical industry.
      One factor limiting the use of FEP is its low throughput, which is attributed in
      part to the dependence of conventional methods on the user's ability to develop
      accurate molecular mechanics (MM) force field parameters for individual drug
      candidates and the time required to complete the process. In an attempt to find
      an FEP method that could eventually be automated, we developed a method that uses
      quantum mechanics (QM) for treating the solute, MM for treating the solute
      surroundings, and the FEP method for computing free-energy differences. The
      thread technique was used in all transformations and proved to be essential for
      the successful completion of the calculations. Relative solvation free energies
      for 10 structurally diverse molecular pairs were calculated, and the results were
      in close agreement with both the calculated results generated by conventional FEP
      methods and the experimentally derived values. While considerably more CPU
      demanding than conventional FEP methods, this method (QM/MM-based FEP) alleviates
      the need for development of molecule-specific MM force field parameters and
      therefore may enable future automation of FEP-based calculations. Moreover,
      calculation accuracy should be improved over conventional methods, especially for
      calculations reliant on MM parameters derived in the absence of experimental
      data.

PMID- 15149208
TI  - Redox modulation of electroosmotic flow in a carbon nanotube membrane.
AB  - Electroosmotic flow (EOF) is widely used to manipulate solutions in capillaries
      and microfluidic devices, and more recently in the nanotubes of a carbon nanotube
      membrane. In all of these applications it is important to control both the rate
      and direction of EOF through the system, independently of the electric field that
      drives EOF. For this reason, there has been considerable recent effort devoted to
      developing ways of modulating the rate and direction of EOF. We describe here a
      new method, and we use the carbon nanotube membrane (CNM) system to demonstrate
      this method. This new method entails coating the inside walls of the carbon
      nanotubes within the CNM with redox-active polymer films. The redox polymer,
      poly(vinylferrocene), can be reversibly electrochemically switched between an
      electrical neutral and a polycationic form. This provides a way for controlling
      both the magnitude and the sign of the surface charge on the nanotube walls,
      which in turn allows for control of both the rate and direction of EOF through
      the CNM.

PMID- 15149209
TI  - Long-lived nuclear spin states in high-field solution NMR.
AB  - Nuclear spin order may be stored in a liquid for a much longer time than the
      longitudinal relaxation time T1, by using rf fields to isolate states of
      different symmetry. The method is demonstrated on a sample containing AX spin
      systems.

PMID- 15149210
TI  - A simple stereocontrolled synthesis of salinosporamide A.
AB  - A simple and effective stereocontrolled synthesis of salinosporamide A has been
      developed. This process, the first synthesis of salinosporamide A, is capable of
      providing the compound in substantial quantities for further biological studies.
      Salinosporamide A was of special interest as a synthetic target because of its
      potent in vitro cytotoxic activity against many tumor cell lines (IC(50) values
      of 10 nM or less).

PMID- 15149211
TI  - Protein Backbone 1H(N)-13Calpha and 15N-13Calpha residual dipolar and J
      couplings: new constraints for NMR structure determination.
AB  - A simple, sensitivity-enhanced experiment was devised for accurate measurement of
      backbone 15N-13Calpha and 1HN-13Calpha couplings in proteins. The measured
      residual dipolar couplings 2DHCA, 1DNCA, 3DHCA, and 2DNCA for protein GB1 display
      very good agreement with the refined NMR structure (PDB code: 3GB1). A Karplus
      type relationship between the one-bond 1JNCA couplings and the backbone dihedral
      psi angles holds, and on the basis of the two-bond 2JNCA couplings a secondary
      structure index can be established.

PMID- 15149213
TI  - Distribution and modification of sorption sites in amphiphilic calixarene-based
      solid lipid nanoparticles from hyperpolarized 129Xe NMR spectroscopy.
AB  - The site distribution and accessibility in amphiphilic calixarenes-based solid
      lipid nanoparticles were determined as a function of lipid chain length using in
      situ 129Xe NMR spectroscopy with flowing hyperpolarized Xe gas. The study
      illustrates that host cavities in as-prepared materials are increasingly occluded
      by the lipid chain for compounds with chain lengths from C6 to C12 and are almost
      completely occluded for C14 and C16 chain lengths. Host cavities present at the
      surface of the particles are still accessible to small atoms (xenon) and organic
      molecules (methylene chloride, etc). The Xe spectra show that the accessible void
      space can be increased remarkably by exposure of the particle surface to suitably
      sized guest molecules that appear to displace the occluding hydrocarbon chains
      from the host cavities by competitive adsorption. This postsynthesis treatment
      thus modifies the state of self-assembly and improves sorption capability. The HP
      Xe NMR approach presented is suitable for small samples (a few milligrams) of
      SLNs, likely also for other biomaterials such as vesicles, model membranes, etc.

PMID- 15149212
TI  - A new method for the stereoselective synthesis of alpha- and beta-glycosylamines
      using the Burgess reagent.
AB  - Although glycosylamines constitute an important group of carbohydrates from the
      standpoint of biology and medicine, methods for their synthesis typically lack
      substrate generality and/or result in variable stereoselectivity, especially in
      complex contexts. In this communication, we report an operationally simple method
      for the synthesis of both alpha- and beta-glycosylamines using the Burgess
      reagent that overcomes many of these limitations in a bare minimum of synthetic
      steps.

PMID- 15149214
TI  - Zinc-induced switching of the nonlinear optical properties of a functionalized
      bis(styryl)benzene.
AB  - A large variation of the nonlinear transmission properties of a cyclen-based
      bis(styryl)benzene can be induced by a small change of the linear absorption
      spectrum upon Zn2+ binding. This result has been interpreted in the frame of a
      sequential two-photon process in which one photon is absorbed from the ground
      state and one photon is absorbed from an excited state.

PMID- 15149216
TI  - Polymer lateral diffusion at the solid-liquid interface.
AB  - Measurements are presented of how polymer surface diffusion at the solid-liquid
      interface is controlled by surface coverage. The method of measurement was
      fluorescence correlation spectroscopy (FCS), and the system was poly(ethylene
      oxide) (PEG) adsorbed onto methyl-terminated self-assembled monolayers in
      buffered aqueous solution. The translational diffusion coefficient at first
      increased with increasing surface concentration, presumably because the number of
      adsorption sites per molecule decreased. Ultimately it slowed by 1 order of
      magnitude, presumably reflecting jamming by neighboring chains.

PMID- 15149215
TI  - A new entry of nucleophiles in rhodium-catalyzed asymmetric 1,4-addition
      reactions: addition of organozinc reagents for the synthesis of 2-aryl-4
      piperidones.
AB  - A rhodium-catalyzed asymmetric 1,4-addition reaction has been applied to the
      synthesis of 2-aryl-4-piperidones. While other conventional nucleophiles fail,
      organozinc reagents have been successfully utilized for the construction of these
      useful compounds in very good yield and enantiomeric excess.

PMID- 15149218
TI  - Autocatalysis and self-inhibition: coupled kinetic phenomena in the chlorite
      tetrathionate reaction.
AB  - The initial rate of formation of chlorine dioxide in the chlorite-tetrathionate
      reaction changes in an unusual fashion. The formal kinetic order of both
      reactants varies over a very wide range. Moreover, chlorite ion behaves not just
      as a simple reactant, but also as a self-inhibitor. A five-step scheme, derived
      from an eight-step mechanism, is proposed in which the autocatalytic formation of
      HOCl plays a central role in accounting for this kinetic behavior.

PMID- 15149219
TI  - Seedless growth of free-standing copper nanowires by chemical vapor deposition.
AB  - Free-standing copper nanowires were synthesized by a chemical vapor deposition
      process at low substrate temperatures using Cu(etac)[P(OEt)3]2 as a precursor.
      The process requires neither templates nor catalysts to produce copper nanowires
      of 70-100 nm in diameter, which exhibited high purity and crystallinity with
      [111] orientation. The grain structures of the films deposited from a series of
      Cu(I) alkyl 3-oxobutanoate complexes indicated that the high precursor stability
      was responsible for the columnar growth of the grains, which was evolved to the
      nanowires eventually.

PMID- 15149217
TI  - Comparison of enzymatic and non-enzymatic nitroethane anion formation:
      thermodynamics and contribution of tunneling.
AB  - In the reaction of nitroalkane oxidase (NAO), the oxidation of nitroalkanes to
      the corresponding aldehydes or ketones is initiated by the deprotonation of the
      neutral nitroalkane. The energetics of nitroethane ionization for both the
      enzymatic and non-enzymatic reactions have been determined by measuring rate
      constants as a function of temperature. At 25 degrees C, the rate constant for
      the acetate-catalyzed reaction is a billionfold smaller than the kcat/Km value
      for NAO. This corresponds to a difference of 12.3 kcal/mol in the free energy of
      activation that is largely due to a difference in the activation enthalpy.
      Analysis of the temperature dependence of the deuterium kinetic isotope effects
      on the reactions yields similar DeltaEa and AH/AD values for the acetate,
      phosphate, and NAO-catalyzed reactions that fall within the semiclassical limits,
      consistent with similar contributions of tunneling to the enzymatic and non
      enzymatic reactions.

PMID- 15149220
TI  - Reactivity control of an allylsilane bearing a 2-(phenylazo)phenyl group by
      photoswitching of the coordination number of silicon.
AB  - Photoswitching of the coordination number of silicon between four and five in
      allyldifluoro[2-(phenylazo)phenyl]silane, which was confirmed by X-ray analysis
      and multinuclear NMR spectroscopy, caused multistep reactions to proceed or stop,
      yielding tetrafluoro[2-(1-allyl-2-phenylhydrazino)phenyl]silicate without
      altering other reaction conditions.

PMID- 15149221
TI  - A tetrahedrally coordinated L3Fe-Nx platform that accommodates terminal nitride
      (Fe(IV)N) and dinitrogen (Fe(I)-N2-Fe(I)) ligands.
AB  - A tetrahedrally coordinated L3Fe-Nx platform that accommodates both terminal
      nitride (L3FeIVN) and dinitrogen (L3FeI-N2-FeIL3) functionalities is described.
      The diamagnetic L3FeIVN species featured has been characterized in solution under
      ambient conditions by multinuclear NMR (1H, 31P, and 15N) and infrared
      spectroscopy. The electronic structure of the title complex has also been
      explored using DFT. The terminal nitride complex oxidatively couples to generate
      the previously reported L3FeI-N2-FeIL3 species. This reaction constitutes a six
      electron transformation mediated by two iron centers. Reductive protonation of
      the nitride complex releases NH3 as a significant reaction product.

PMID- 15149222
TI  - Diastereomer assignment of an olefin-linked bis-paracyclophane by ion mobility
      mass spectrometry.
AB  - trans-1,2-Bis([2.2]paracyclophanyl)ethene (1) exists as a pair of diastereomers
      whose conformations, and thus effective collision cross sections, are quite
      different. The two forms can be obtained by different transition metal-catalyzed
      reactions. To assign meso and racemic structures, a novel method is reported in
      which experimental gas-phase ion mobility data are compared with theoretical
      structures obtained from molecular mechanics calculations.

PMID- 15149223
TI  - Completely automated, highly error-tolerant macromolecular structure
      determination from multidimensional nuclear overhauser enhancement spectra and
      chemical shift assignments.
AB  - The major rate-limiting step in high-throughput NMR protein structure
      determination involves the calculation of a reliable initial fold, the
      elimination of incorrect nuclear Overhauser enhancement (NOE) assignments, and
      the resolution of NOE assignment ambiguities. We present a robust approach to
      automatically calculate structures with a backbone coordinate accuracy of 1.0-1.5
      A from datasets in which as much as 80% of the long-range NOE information (i.e.,
      between residues separated by more than five positions in the sequence) is
      incorrect. The current algorithm differs from previously published methods in
      that it has been expressly designed to ensure that the results from successive
      cycles are not biased by the global fold of structures generated in preceding
      cycles. Consequently, the method is highly error tolerant and is not easily
      funnelled down an incorrect path in either three-dimensional structure or NOE
      assignment space. The algorithm incorporates three main features: a linear energy
      function representation of the NOE restraints to allow maximization of the number
      of simultaneously satisfied restraints during the course of simulated annealing;
      a method for handling the presence of multiple possible assignments for each NOE
      cross-peak which avoids local minima by treating each possible assignment as if
      it were an independent restraint; and a probabilistic method to permit both
      inactivation and reactivation of all NOE restraints on the fly during the course
      of simulated annealing. NOE restraints are never removed permanently, thereby
      significantly reducing the likelihood of becoming trapped in a false minimum of
      NOE assignment space. The effectiveness of the algorithm is demonstrated using
      completely automatically peak-picked experimental NOE data from two proteins:
      interleukin-4 (136 residues) and cyanovirin-N (101 residues). The limits of the
      method are explored using simulated data on the 56-residue B1 domain of
      Streptococcal protein G.

PMID- 15149224
TI  - Highly efficient photochemical 2'-deoxyribonolactone formation at the diagonal
      loop of a 5-iodouracil-containing antiparallel G-quartet.
AB  - To explore the structure-dependent hydrogen abstraction in antiparallel and
      parallel G-quartet DNA structures, the photochemical reactivity of 5-iodouracil
      ((I)U)-containing human telomeric DNA 22-mers was investigated under the 302 nm
      UV irradiation conditions. We discovered that only antiparallel ODN 4, in which
      the second T residue in the diagonal loop of the antiparallel G-quartet is
      substituted with (I)U, was rapidly consumed as compared with parallel ODN 4 and
      the other (I)U-containing 22-mers under the irradiation conditions. Product
      analysis of the photolyzate of antiparallel ODN 4 indicated that a 2'
      deoxyribonolactone residue was effectively produced at the 5' side of the (I)U
      residue in the diagonal loop. Photochemical 2'-deoxyribonolactone formation was
      also found in the (I)U-containing diagonal loop of antiparallel G-quartets
      d(GGGGTTT(I)UGGGG)(2) and d(GGGGTT(I)UTGGGG)(2), whereas the reaction did not
      occur at other DNA structures, including the single-stranded form, the loop
      region of the hairpin, and linear four-stranded G-quartets. The results clearly
      indicate that this type of 2'-deoxyribonolactone formation efficiently occurrs
      only in the diagonal loop of the antiparallel G-quartet. Furthermore, we found
      that 2'-deoxyribonolactone was formed at the (I)U-containing G-rich sequence of
      the IgG switch regions and the 5' termini of the Rb gene, suggesting the
      formation of an antiparallel G-quartet with a diagonal loop in these sequences.
      These results suggest that the present photochemical method can be used as a
      specific probe for the antiparallel G-quartet with the diagonal loop.

PMID- 15149225
TI  - Hydrogen bond driven chemical reactions: Beckmann rearrangement of cyclohexanone
      oxime into epsilon-caprolactam in supercritical water.
AB  - Recent experiments have shown that supercritical water (SCW) has the ability to
      accelerate and make selective synthetic organic reactions, thus replacing the
      common but environmentally harmful acid and basic catalysts. In an attempt to
      understand the intimate mechanism behind this observation, we analyze, via first
      principles molecular dynamics, the Beckmann rearrangement of cyclohexanone oxime
      into epsilon-caprolactam in supercritical water, for which accurate experimental
      evidence has been reported. Differences in the wetting of the hydrophilic parts
      of the solute, enhanced by SCW, and the disrupted hydrogen bond network are shown
      to be crucial in triggering the reaction and in making it selective. Furthermore,
      the enhanced concentrations of H(+) in SCW play an important role in starting the
      reaction.

PMID- 15149226
TI  - Mechanism and regioselectivity of reductive elimination of pi-allylcopper (III)
      intermediates.
AB  - Reductive elimination of a pi-allylcopper(III) compound leading to the formation
      of a C-C bond on an allylic terminal has been considered to occur via the
      corresponding sigma-allylcopper(III) species. The present B3LYP density
      functional study has shown however that the C-C bond formation occurs directly
      from the pi-allyl complex via an enyl[sigma+pi]-type transition state, which has
      structural features different from a simple sigma-allylcopper(III) intermediate.
      In the case of unsymmetrically substituted pi-allylcopper(III) compound that has
      a partial sigma-allylcopper(III) structure, the reductive elimination occurs
      preferentially at the sigma-bonded allylic terminal since, in this way, the
      copper atom can recover most effectively its d-electrons shared with the allyl
      system. The regioselectivity of the reductive elimination of a substituted pi
      allylcopper(III) intermediate is mainly controlled by the electronic effect, and
      correlated well to the Hammett sigma(p)(+) constant. The analyses revealed
      mechanistic kinship between the allylic substitution and the conjugate addition
      reaction of organocopper reagents.

PMID- 15149227
TI  - Self-assembling molecular trees containing octa-p-phenylene: from nanocrystals to
      nanocapsules.
AB  - Tree-shaped molecules consisting of octa-p-phenylene as a stem segment and
      oligoether dendrons as a flexible head were synthesized and characterized. The
      molecular tree based on a small flexible head self-assembles into a lamellar
      structure, whereas the molecule based on a larger headgroup self-assembles into a
      discrete heptameric bundle that organizes into a 3-D primitive orthorhombic
      supercrystals, as confirmed by X-ray scatterings and transmission electron
      microscopic (TEM) observations. Optical studies revealed that the absorption and
      emission maxima and absorption edge of the 3-D structure shift to higher energy
      compared to those of the lamellar structure. The molecules in dilute solution
      (THF/water = 1:10 v/v) were observed to self-assemble into capsule-like hollow
      aggregates, as confirmed by dynamic and static light scatterings, scanning
      electron microscopy (SEM), and TEM investigations. These results demonstrate that
      tree-shaped molecules are capable of packing into organized discrete nanocrystals
      with parallel arrangement as well as hollow nanocapsules with radial arrangement,
      depending on the presence of selective solvents for flexible headgroup.

PMID- 15149228
TI  - Subphthalocyanines: tuneable molecular scaffolds for intramolecular electron and
      energy transfer processes.
AB  - A series of four subphthalocyanine-C(60) fullerene dyads have been prepared
      through axial functionalization of the macrocycle with m-hydroxybenzaldehyde and
      a subsequent dipolar cycloaddition reaction. The subphthalocyanine moiety has
      been peripherally functionalized with substituents of different electronic
      character, namely fluorine or iodine atoms and ether or amino groups, thus
      reaching a control over its electron-donating properties. This is evidenced in
      cyclic voltammetry experiments by a progressive shift to lower potentials, by ca.
      200 mV, of the first oxidation event of the SubPc unit in the dyads. As a
      consequence, the energy level of the SubPc(*)(+)-C(60)(*)(-) charge-transfer
      state may be tuned so as to compete with energy transfer deactivation pathways
      upon selective excitation of the SubPc component. For instance, excitation of
      those systems where the level of the radical pair lies high in energy triggers a
      sequence of exergonic photophysical events that comprise (i) nearly quantitative
      singlet-singlet energy transfer to the C(60) moiety, (ii) fullerene intersystem
      crossing, and (iii) triplet-triplet energy transfer back to the SubPc. On the
      contrary, the stabilization of the SubPc(*)(+)-C(60)(*)(-) radical pair state by
      increasing the polarity of the medium or by lowering the donor-acceptor redox gap
      causes charge transfer to dominate. In the case of 1c in benzonitrile, the thus
      formed radical pair has a lifetime of 0.65 ns and decays via the energetically
      lower lying triplet excited state. Further stabilization is achieved for dyad 1d,
      whose charge-transfer state would lie now below both triplets. The radical pair
      lifetime consequently increases in more than 2 orders of magnitude with respect
      to 1c and presents a significant stabilization in less polar solvents, revealing
      a low reorganization energy for this kind of SubPc-C(60) systems.

PMID- 15149229
TI  - Directed assembly of transition-metal-coordinated molecular loops and squares
      from salen-type components. Examples of metalation-controlled structural
      conversion.
AB  - A series of transition-metal-containing molecular "loops" and "squares" has been
      prepared via a directed-assembly approach and characterized. The molecular loops
      were prepared from the reaction of cis-(PEt(3))(2)Pt(OTf)(2) with bis(4-pyridyl)
      functionalized free-base salen-type ligands. Zn(II)-metalation of the salen-type
      ligands in the molecular loops converts the loops to molecular squares.
      Alternatively, the squares can be obtained by the directed assembly of cis
      (PEt(3))(2)Pt(OTf)(2) and bis(4-pyridyl)-functionalized Zn(II)-salen-type
      ligands. A concentration-dependent dynamic equilibrium between cyclic species was
      observed when bis(3-pyridyl)-functionalized free-base salen-type ligand was
      employed in the reaction. Zn(II) or Cr(III) metalation of the free-base ligand
      shifted the equilibrium to the single dimeric species. The incorporation of
      multiple reactive metal sites into a single, cavity-containing supramolecular
      structure points toward catalytic applications for these new assemblies.

PMID- 15149230
TI  - A synthetic reaction network: chemical amplification using nonequilibrium
      autocatalytic reactions coupled in time.
AB  - This article reports a functional chemical reaction network synthesized in a
      microfluidic device. This chemical network performs chemical 5000-fold
      amplification and shows a threshold response. It operates in a feedforward manner
      in two stages: the output of the first stage becomes the input of the second
      stage. Each stage of amplification is performed by a reaction autocatalytic in
      Co(2+). The microfluidic network is used to maintain the two chemical reactions
      away from equilibrium and control the interactions between them in time. Time
      control is achieved as described previously (Angew. Chem., Int. Ed. 2003, 42,
      768) by compartmentalizing the reaction mixture inside plugs which are aqueous
      droplets carried through a microchannel by an immiscible fluorinated fluid.
      Autocatalytic reaction displayed sensitivity to mixing; more rapid mixing
      corresponded to slower reaction rates. Synthetic chemical reaction networks may
      help understand the function of biochemical reaction networks, the goal of
      systems biology. They may also find practical applications. For example, the
      system described here may be used to detect visually, in a simple format,
      picoliter volumes of nanomolar concentrations of Co(2+), an environmental
      pollutant.

PMID- 15149231
TI  - Mechanism of palladium-catalyzed diene cyclization/hydrosilylation: direct
      observation of intramolecular carbometalation.
AB  - The results of kinetic, deuterium-labeling, and low-temperature NMR studies have
      established a mechanism for the palladium-catalyzed cyclization/hydrosilylation
      of dimethyl diallylmalonate (1) with triethylsilane involving rapid, irreversible
      conversion of the palladium silyl complex [(phen)Pd(SiEt(3))(NCAr)](+) [BAr(4)](
      ) [Ar = 3,5-C(6)H(3)(CF(3))(2)] (4b) and 1 to the palladium 5-hexenyl chelate
      complex [(phen)Pd[eta(1),eta(2)
      CH(CH(2)SiEt(3))CH(2)C(CO(2)Me)(2)CH(2)CH=CH(2)]](+) [BAr(4)](-) (5), followed by
      intramolecular carbometalation of 5 to form the palladium cyclopentylmethyl
      complex trans-[(phen)Pd[CH2CHCH2C(CO2Me)2CH2CHCH2SiEt3](NCAr)]+ [BAr4]- (6), and
      associative silylation of 6 to release 3 and regenerate 4b.

PMID- 15149233
TI  - Oxidation of alkylarenes by nitrate catalyzed by polyoxophosphomolybdates:
      synthetic applications and mechanistic insights.
AB  - Alkylarenes were catalytically and selectively oxidized to the corresponding
      benzylic acetates and carbonyl products by nitrate salts in acetic acid in the
      presence of Keggin type molybdenum-based heteropolyacids,
      H(3+)(x)()PV(x)()Mo(12)(-)(x)()O(40) (x = 0-2). H(5)PV(2)Mo(10)O(40) was
      especially effective. For methylarenes there was no over-oxidation to the
      carboxylic acid contrary to what was observed for nitric acid as oxidant. The
      conversion to the aldehyde/ketone could be increased by the addition of water to
      the reaction mixture. As evidenced by IR and (15)N NMR spectroscopy, initially
      the nitrate salt reacted with H(5)PV(2)Mo(10)O(40) to yield a
      N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] intermediate. In an electron-transfer reaction,
      the proposed N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] complex reacts with the alkylarene
      substrate to yield a radical-cation-based donor-acceptor intermediate,
      N(IV)O(2)[H(4)PV(2)Mo(10)O(40)]-ArCH(2)R(+)(*). Concurrent proton transfer yields
      an alkylarene radical, ArCHR(*), and NO(2). Alternatively, it is possible that
      the N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] complex abstracts a hydrogen atom from
      alkylarene substrate to directly yield ArCHR(*) and NO(2). The electron transfer
      proton transfer and hydrogen abstraction scenarios are supported by the
      correlation of the reaction rate with the ionization potential and the bond
      dissociation energy at the benzylic positions of the alkylarene, respectively,
      the high kinetic isotope effect determined for substrates deuterated at the
      benzylic position, and the reaction order in the catalyst. Product selectivity in
      the oxidation of phenylcyclopropane tends to support the electron transfer-proton
      transfer pathway. The ArCHR(*) and NO(2) radical species undergo heterocoupling
      to yield a benzylic nitrite, which undergoes hydrolysis or acetolysis and
      subsequent reactions to yield benzylic acetates and corresponding aldehydes or
      ketones as final products.

PMID- 15149232
TI  - Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some
      preliminary findings as to SAR.
AB  - A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is
      provided. A key feature of the syntheses involved installation of a cis
      propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The
      scope and mechanism of the enamide-forming reaction are discussed. Also provided
      are some preliminary results from SAR studies. It was found that simplified
      analogues can retain the full potency of proteasome inhibition.

PMID- 15149234
TI  - Transformation of acyclic alkenes to hydrido carbynes by (PNP(R))Re complexes.
AB  - Synthesis of (PNP(R))ReOCl(2) (PNP(R) = (R(2)PCH(2)SiMe(2))(2)N, R = (i)()Pr, Cy,
      and (t)()Bu) from (Me(2)S)(2)ReOCl(3) and (PNP(R))MgCl is described. Magnesium
      and H(2) convert (PNP(R))ReOCl(2) first to (PNP(R))ReO(H)(2) and then to
      (PNP(R))Re(H)(4), the last being an operationally unsaturated species which can
      bind PMe(3) or p-toluidine. Acyclic alkenes react with (PNP(R))Re(H)(4) at 22
      degrees C to give first (PNP(R))Re(H)(2)(olefin) and then (PNP(R))ReH(carbyne),
      in equilibrium with its eta(2)-olefin adduct. Re can also migrate to the terminal
      carbon of internal olefins to form a carbyne complex. Allylic C-SiMe(3) or C
      NH(2) bonds are not broken, but OEt, OPh, and F vinyl substituents (X) are
      ultimately cleaved from carbon to give the ReC-CH(3) complex and liberate HX. DFT
      calculations, together with detection of intermediates for certain olefins, help
      to define a mechanism for these conversions.

PMID- 15149237
TI  - Heterogeneous growth of metal clusters from solutions of seed nanoparticles.
AB  - We describe the solution growth of a series of discrete sized generations of Au
      nanoparticles by the heterogeneous deposition of atoms onto monodisperse seed
      nanocrystals. The growth process was studied using size-exclusion chromatography
      (SEC) and transmission electron microscopy (TEM). The size dispersion of each
      generation was determined from the SEC elution line widths and the spectral
      homogeneity of the elution peaks. The heterogeneous deposition of various amounts
      of Ag on Au nanocrystals and Au on Ag nanocrystals using the same synthetic
      protocol is also described. The effect of such deposition on the optical
      absorbance of each generation of larger clusters was measured during SEC using an
      on-line photodiode array absorbance detector.

PMID- 15149236
TI  - A comparative study of pi-arene-bridged lanthanum arylamide and aryloxide dimers.
      Solution behavior, exchange mechanisms, and X-ray crystal structures of La2(NH
      2,6-iPr2C6H3)6, La(NH-2,6-iPr2C6H3)3(THF)3, and La(NH-2,6-iPr2C6H3)3(py)2.
AB  - Reaction of 3 equiv of 2,6-diisopropylaniline with La[N(SiMe(3))(2)](3) produces
      the dimeric species La(2)(NHAr)(6) (1). X-ray crystallography reveals a
      centrosymmetric structure, where the dimeric unit is bridged by intermolecular
      eta(6)-arene interactions of a unique arylamide ligand attached to an adjacent
      metal center. Exposure of 1 to THF results in formation of the monomeric tris-THF
      adduct La(NHAr)(3)(THF)(3) (2), which was shown by X-ray crystallography to
      maintain a fac-octahedral structure in the solid state. (1)H NMR spectroscopy
      illustrates that the binding of THF to 1 to form 2 is reversible and removal of
      THF under vacuum regenerates dimeric 1. Addition of pyridine to 1 yields the
      monomeric bis-pyridine adduct La(NHAr)(3)(py)(2) (3), which exhibits a distorted
      trigonal-bipyramidal La metal center. Solution (1)H NMR, IR, and Raman
      spectroscopy indicate that the pi-arene-bridged dimeric structure of 1 is
      maintained in solution. Variable-temperature (1)H NMR spectroscopic
      investigations of 1 are consistent with a monomer-dimer equilibrium at elevated
      temperature. In contrast, variable-temperature (1)H NMR spectroscopic
      investigations of the aryloxide analogue La(2)(OAr)(6) (4) show that the bridging
      and terminal aryloxide groups exchange by a mechanism in which the dimeric nature
      of the compound is retained. Density functional theory (DFT) calculations were
      carried out on model compounds La(2)(OC(6)H(5))(6), La(2)(NHC(6)H(5))(6), and
      (C(6)H(5)R)La(XC(6)H(5))(3), where X = O or NH and R = H, OH, or NH(2). The
      formation of eta(6)-arene interactions is energetically favored over monomeric
      LaX(3) (X = OPh or NHPh) with the aryloxide pi-arene interaction being stronger
      than the arylamide pi-arene interaction. Calculation of vibrational frequencies
      reveals the origin of the observed IR spectral behavior of both
      La(2)(OC(6)H(5))(6) and La(2)(NHC(6)H(5))(6), with the higher energy nu(C=C)
      stretch due to terminal ligands and the lower energy stretch associated with the
      bridging ligands.

PMID- 15149235
TI  - The effects of axial ligands on electron distribution and spin states in iron
      complexes of octaethyloxophlorin, intermediates in heme degradation.
AB  - The results presented here show that the nature of the axial ligand can alter the
      distribution of electrons between the metal and the porphyrin in complexes where
      there is an oxygen atom replacing one of the meso protons. The complexes (1
      MeIm)(2)Fe(III)(OEPO) and (2,6-xylylNC)(2)Fe(II)(OEPO(*)) (where OEPO is the
      trianionic octaethyloxophlorin ligand and OEPO(*) is the dianionic
      octaethyloxophlorin radical) were prepared by addition of an excess of the
      appropriate axial ligand to a slurry of [Fe(III)(OEPO)](2) in chloroform under
      anaerobic conditions. The magnetic moment of (2,6-xylylNC)(2)Fe(II)(OEPO(*)) is
      temperature invariant and consistent with a simple S = (1)/(2) ground state. This
      complex with an EPR resonance at g = 2.004 may be considered as a model for the
      free-radical like EPR signal seen when the meso-hydroxylated heme/heme oxygenase
      complex is treated with carbon monoxide. In contrast, the magnetic moment of (1
      MeIm)(2)Fe(III)(OEPO) drops with temperature and indicates a spin-state change
      from an S = (5)/(2) or an admixed S = (3)/(2),(5)/(2) state at high temperatures
      (near room temperature) to an S = (1)/(2) state at temperatures below 100 K. X
      ray diffraction studies show that each complex crystallizes in centrosymmetric
      form with the expected six-coordinate geometry. The structure of (1
      MeIm)(2)Fe(III)(OEPO) has been determined at 90, 129, and 296 K and shows a
      gradual and selective lengthening of the Fe-N(axial bond). This behavior is
      consistent with population of a higher spin state at elevated temperatures.

PMID- 15149238
TI  - Site-specific fabrication of nanoscale heterostructures: local chemical
      modification of GaN nanowires using electrochemical dip-pen nanolithography.
AB  - This article describes a new method for site-specific, atomic force microscope
      (AFM) fabrication of nanowire heterostructures using electrochemical dip-pen
      nanolithography (E-DPN). We have demonstrated that E-DPN is ideally suited for
      the in situ modification of nanoscale electronic devices; the AFM tip and the
      nanowire device can be used as electrodes and the reactants for the modification
      can be introduced by coating them onto the AFM tip. Specifically, we have created
      GaN nanowire heterostructures by a local electrochemical reaction between the
      nanowire and a tip-applied KOH "ink" to produce gallium nitride/gallium oxide
      heterostructures. By controlling the ambient humidity, reaction voltage, and
      reaction time, good control over the modification geometry is obtained.
      Furthermore, after selective chemical etching of gallium oxide, unique diameter
      modulated nanowire structures can be produced. Finally, we have demonstrated the
      unique device fabrication capabilities of this technique by performing in situ
      modification of GaN nanowire devices and characterizing the device electronic
      transport properties. These results demonstrate that small modifications of
      nanowire devices can lead to large changes in the nanowire electron transport
      properties.

PMID- 15149239
TI  - A new thermoelectric material: CsBi4Te6.
AB  - The highly anisotropic material CsBi(4)Te(6) was prepared by the reaction of
      Cs/Bi(2)Te(3) around 600 degrees C. The compound crystallizes in the monoclinic
      space group C2/m with a = 51.9205(8) A, b = 4.4025(1) A, c = 14.5118(3) A, beta =
      101.480(1) degrees, V = 3250.75(11) A(3), and Z = 8. The final R values are R(1)
      = 0.0585 and wR(2) = 0.1127 for all data. The compound has a 2-D structure
      composed of NaCl-type [Bi(4)Te(6)] anionic layers and Cs(+) ions residing between
      the layers. The [Bi(4)Te(6)] layers are interconnected by Bi-Bi bonds at a
      distance of 3.2383(10) A. This material is a narrow gap semiconductor.
      Optimization studies on the thermoelectric properties with a variety of doping
      agents show that the electrical properties of CsBi(4)Te(6) can be tuned to yield
      an optimized thermoelectric material which is promising for low-temperature
      applications. SbI(3) doping resulted in p-type behavior and a maximum power
      factor of 51.5 microW/cm.K(2) at 184 K and the corresponding ZT of 0.82 at 225 K.
      The highest power factor of 59.8 microW/cm.K(2) at 151 K was obtained from 0.06%
      Sb-doped material. We report here the synthesis, physicochemical properties,
      doping characteristics, charge-transport properties, and thermal conductivity.
      Also presented are studies on n-type CsBi(4)Te(6) and comparisons to those of p
      type.

PMID- 15149240
TI  - Projection-reconstruction technique for speeding up multidimensional NMR
      spectroscopy.
AB  - The acquisition of multidimensional NMR spectra can be speeded up by a large
      factor by a projection-reconstruction method related to a technique used in X-ray
      scanners. The information from a small number of plane projections is used to
      recreate the full multidimensional spectrum in the familiar format. Projections
      at any desired angle of incidence are obtained by Fourier transformation of time
      domain signals acquired when two or more evolution intervals are incremented
      simultaneously at different rates. The new technique relies on an established
      Fourier transform theorem that relates time-domain sections to frequency-domain
      projections. Recent developments in NMR instrumentation, such as increased
      resolution and sensitivity, make fast methods for data gathering much more
      practical for protein and RNA research. Hypercomplex Fourier transformation
      generates projections in symmetrically related pairs that provide two independent
      "views" of the spectrum. A new reconstruction algorithm is proposed, based on the
      inverse Radon transform. Examples are presented of three- and four-dimensional
      NMR spectra of nuclease A inhibitor reconstructed by this technique with
      significant savings in measurement time.

PMID- 15149241
TI  - Damage to model DNA fragments from very low-energy (<1 eV) electrons.
AB  - Although electrons having enough energy to ionize or electronically excite DNA
      have long been known to cause strand breaks (i.e., bond cleavages), only recently
      has it been suggested that even lower-energy electrons (most recently 1 eV and
      below) can also damage DNA. The findings of the present work suggest that, while
      DNA bases can attach electrons having kinetic energies in the 1 eV range and
      subsequently undergo phosphate-sugar O-C sigma bond cleavage, it is highly
      unlikely (in contrast to recent suggestions) that electrons having kinetic
      energies near 0 eV can attach to the phosphate unit's P=O bonds. Electron kinetic
      energies in the 2-3 eV range are required to attach directly to DNA's phosphate
      group's P=O pi orbital and induce phosphate-sugar O-C sigma bond cleavages if the
      phosphate groups are rendered neutral (e.g., by nearby counterions). Moreover,
      significant activation barriers to C-O bond breakage render the rates of both
      such damage mechanisms (i.e., P=O-attached and base-attached) slow as compared to
      electron autodetachment and to other damage processes.

PMID- 15149243
TI  - Local and global chirality at surfaces: succinic acid versus tartaric acid on
      Cu110.
AB  - A detailed comparison of tartaric acid (HOOC-CHOH-CHOH-COOH) and succinic acid
      (HOOC-CH(2)-CH(2)-COOH) molecules on a Cu(110) surface is presented with a view
      to elucidate how the two-dimensional chirality exhibited by such robust,
      chemisorbed systems is affected when both OH groups of the former molecule are
      replaced with H groups, a stereochemical change that leaves the metal-bonding
      functionalities of the molecule untouched but destroys both chiral centers. It is
      found that this change does not significantly affect the thermodynamically
      preferred chemical forms that are adopted, namely the doubly deprotonated
      bicarboxylate at low coverages (theta </= (1)/(6) ML) and the singly deprotonated
      monocarboxylate at higher coverage. However, the kinetics of phase formation are
      significantly affected so that the conditions required for self-assembling
      pertinent two-dimensional chiral phases alter substantially. For both molecules,
      two-dimensional assembly is found to depend strongly on the nature of the local
      adsorption motif created, with each motif essentially acting as a "synthon" for
      the supramolecular assembly. In this respect, it seems that molecule-metal
      bonding interactions define the general self-assembly structure. The
      presence/absence of the OH groups, instead, cause a subtler, second-order effect
      on the finer details of the self-assembled structure. Finally, the creation of
      chirality in the achiral succinate system is shown to arise from adsorption
      induced asymmetrization, inducing point chirality via molecular distortion and/or
      metal reconstruction of the local adsorption unit. This chiral adsorption unit is
      then responsible for creating chiral supramolecular through-space and through
      metal interactions that propagate a chiral organization. However, the achirality
      of the succinate ensures that nucleation points of either chirality are equally
      created, producing a racemic conglomerate of coexisting mirror domains. It is in
      this aspect that the uniquely aligned OH groups of the rigid bitartrate system
      wield the greatest effect, by favoring one distortion/reconstruction for the
      (R,R)-bitartrate and its mirror image distortion/reconstruction for the (S,S)
      enantiomer, creating surfaces that are globally chiral on the macroscopic scale.
      So overall, the OH groups do not dictate the general nature of the assembly but
      are critical as chiral propagators, breaking the degeneracy and thus promoting
      asymmetry to chirality.

PMID- 15149242
TI  - Initial structure modification of tetrahedral to planar nickel(II) in a nickel
      iron-sulfur cluster related to the C-cluster of carbon monoxide dehydrogenase.
AB  - A method has been devised that creates a planar Ni(II) site from a tetrahedral
      site in a NiFe(3)S(4) cubane-type cluster. Reaction of
      [(Ph(3)P)NiFe(3)S(4)(LS(3))](2)(-) (2) with 1,2-bis(dimethylphosphino)ethane
      affords [(dmpe)NiFe(3)S(4)(LS(3))](2)(-) (3), isolated in ca. 45% yield as
      (Et(4)N)(2)[3a].2.5MeCN and (Et(4)N)(2)[3b].0.25MeCN, both of which occur in
      triclinic space group P. Each crystalline form contains two crystallographically
      inequivalent clusters with the same overall structure but slightly different
      dimensions. The cluster is bound by three thiolate terminal ligands to semirigid
      cavitand ligand LS(3). The NiFe(3)S(4) core contains three tetrahedral sites, one
      Fe(micro(3)-S)(3)(SR) and two Fe(micro(3)-S)(2)(micro(2)-S)(SR) with normal
      metric features, and one distorted square planar Ni(micro(3)-S)(2)P(2) site in a
      Ni(micro(3)-S)(2)Fe face with mean bond lengths Ni-P = 2.147(9) A and Ni-S =
      2.29(2) A. The opposite Fe(2)(micro(3)-S)(micro(2)-S) face places the micro(2)-S
      atom at nonbonding and variable distances (2.60-2.90 A) above the nickel atom.
      Binding of the strong-field ligand dmpe results in a planar Ni(II) site and
      deconstruction of the full cubane geometry. The structure approximates that
      established crystallographically in the C-cluster of C. hydrogenoformans carbon
      monoxide dehydrogenase whose NiFe(4)S(4) core contains a planar NiS(4) site and
      three tetrahedral FeS(4) sites in a fragment that is bridged by sulfide atoms to
      an exo iron atom. Mossbauer studies of polycrystalline samples containing both
      clusters 3a and 3b reveal the presence of at least two cluster types. The
      spectroscopically best defined cluster accounts for ca. 54% of total iron and
      exhibits hyperfine interactions quite similar to those reported for the S =
      (5)/(2) state of the protein-bound cubane-type cluster [ZnFe(3)S(4)](1+), whose
      Mossbauer spectrum revealed the presence of a high-spin Fe(2+) site and a
      delocalized Fe(2.5+)Fe(2.5+) pair. Development of reactions leading to a planar
      nickel and a sulfide-bridged iron atom is requisite to attainment of a synthetic
      analogue of this complex protein-bound cluster. This work demonstrates a
      tetrahedral (2) --> planar (3) Ni(II) stereochemical conversion can be effected
      by binding of ligands that generate a sufficiently strong in-plane ligand field
      (dmpe = 1,2-bis(dimethylphosphino)ethane, LS(3) = 1,3,5-tris((4,6-dimethyl-3
      mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)benzene(3-)).

PMID- 15149246
TI  - Differential conductance switching of planar tunnel junctions mediated by
      oxidation/reduction of functionally protected ferrocene.
AB  - Planar tunnel junctions were fabricated by self-assembling 1,1'-
      ferrocenedicarboxylic acid (FDCA) onto native oxides of thermally deposited
      aluminum films and subsequently depositing a second aluminum film. Junctions were
      characterized using Reflection-Absorption Fourier Transform Infrared Spectroscopy
      (RAIRS) and current-voltage (I-V) spectroscopy. Before deposition of the second
      aluminum film, RAIRS of FDCA and ferrocenecarboxylic acid (FCA) films revealed
      COO(-), C=O, and Fc ring stretching modes, indicating that both types of
      molecules can interact strongly with the oxide and remain intact. After
      deposition, systems exhibited prominent COO(-) modes and weakened C=O modes,
      indicating further reaction with aluminum/aluminum oxide. Fc ring modes persisted
      in FDCA systems but disappeared in FCA systems, suggesting that the second COOH
      group in the FDCA molecule can act as a protecting group for the ferrocene
      moiety. Cyclic I-V measurements of FDCA tunnel junction systems revealed very
      strong ( approximately 10-fold) hysteretic differential conductance switching
      that was both reversible and stable. Control measurements using as prepared
      junctions, as well as junctions containing 1,6-hexanedioic acid, 1,9-nonanedioic
      acid, 1,4-dibenzoic acid, or FCA revealed only very weak ( approximately 10%)
      differential conductance changes. We attribute FDCA junction switching to barrier
      profile modifications induced by oxidation/reduction of the functionally
      protected ferrocene moieties.

PMID- 15149244
TI  - Atropisomerization, C-H activation, and dissociative substitution at some
      biphenyl platinum(II) complexes.
AB  - The reaction of 2,2'-dilithiumbiphenyl with cis-[PtCl(2)(SEt(2))(2)] at -10
      degrees C in diethyl ether not only leads to the main product [Pt(2)(micro
      SEt(2))(2)(bph)(2)], containing the planar 2,2'-biphenyl dianion (bph(2)(-)), but
      also forms a new dinuclear platinum(II) compound of formula [Pt(2)(micro
      SEt(2))(2)(Hbph)(4)], 1a (Hbph(-) = eta(1)-biphenyl monoanion), in which each
      metal is in a square-planar environment. NMR spectroscopy and molecular mechanics
      (MMFF) calculations were used to characterize 1a. The results suggest that the
      favored conformation for the four Hbph biphenyl groups is alphabetabetaalpha. In
      chloroform solution, 1a undergoes atropisomerization to 1b (alphabetaalphabeta)
      (k(is) = 1.03 x 10(-)(4) s(-)(1), at 298 K) that subsequently cyclometalates
      (k(obs) = 4.48 x 10(-)(6) s(-)(1), at 298 K) to yield [Pt(2)(micro
      SEt(2))(2)(bph)(2)] and biphenyl. Both processes, atropisomerization and C-H
      activation, presumably involve preliminary thioether bridge splitting. The
      dinuclear complex 1a has been shown to be a versatile and useful precursor to a
      variety of mononuclear eta(1)-biphenyl platinum(II) complexes. By reaction with
      diethyl sulfide, dimethyl sulfoxide, or with rigid dinitrogen containing ligands,
      such as 2,2'-bipyridine or 1,10-phenanthroline, complexes cis
      [Pt(Hbph)(2)(dmso)(2)] 3, cis-[Pt(Hbph)(2)(SEt(2))(2)] 4, [Pt(Hbph)(2)(bpy)] 5,
      and [Pt(Hbph)(2)(phen)] 6 were obtained, respectively. The crystal structures of
      compounds 5 and 6 were determined. Only the head-to-tail isomer of these
      compounds was recognized in the solid state and in solution, where restricted
      rotation around the Pt-C bond prevents interconversion to the head-to-head form.
      A detailed kinetic study of ligand (dmso) exchange and substitution (by 2,2'
      bipyridine and 1,10-phenanthroline) has been performed on complex 3 in CDCl(3)
      and toluene-d(8) by (1)H NMR magnetization transfer experiments, and in toluene
      by UV/vis spectroscopy, respectively. The rates of both processes show no
      dependence on ligand concentration, the rate of ligand substitution being in
      reasonable agreement with that of ligand exchange at the same temperature. The
      kinetics are characterized by largely positive entropies of activation. The
      results are consistent with a dissociative mode of activation analogous to the
      pattern already found for compounds with a similar [Pt(C,C)(S,S)] set of
      coordinating ligands. The role of ML(3) d(8) T-shaped 14-electron species, as
      elusive reaction intermediates or structurally characterized compounds, is
      discussed.

PMID- 15149245
TI  - Gas-phase H/D exchange of sodiated glycine oligomers with ND3: exchange kinetics
      do not reflect parent ion structures.
AB  - H/D exchange is a method commonly used to probe molecular structure. The majority
      of studies in the gas phase have involved protonated molecular ions. The present
      study gives attention to molecular ions formed by coordination with a sodium ion.
      In particular, ND(3) is reacted with sodiated glycine oligomers, Gly(n)(), where
      n = 1-5, and the results are interpreted using density functional calculations.
      Experimentally, Gly(1)Na(+), Gly(4)Na(+), and Gly(5)Na(+) all undergo three fast
      exchanges with ND(3), while Gly(2)Na(+) and Gly(3)Na(+) undergo one fast and two
      slow exchanges with ND(3). The methyl esters Gly(3)OMeNa(+) and Gly(5)OMeNa(+) do
      not exchange with ND(3). In agreement with earlier experimental studies,
      theoretical calculations show that the lowest-energy conformers of the sodiated
      glycine oligomers are charge-solvated structures. Calculations further indicate
      that, in the process of H/D exchange with ND(3), sodiated monoglycine and
      tetraglycine adopt zwitterionic structures, sodiated diglycine adopts a salt
      bridge form, and sodiated triglycine takes on an ion-stabilized ion pair form.
      Sodiated monoglycine and diglycine exchange via an onium-ion mechanism. The
      proposed exchange mechanisms require a carboxylic acid hydrogen to complete the
      exchange, which is in agreement with the experimental results showing that no
      exchange occurs with methyl ester glycine oligomers. These studies clearly
      demonstrate that, in the process of H/D exchange, noncovalent complexation of the
      exchange reagent provides the energy required to access intermediates
      structurally distinct from the parent ions. H/D exchange is facile for these
      intermediates. Contrary to the assumption often expressed in earlier studies, H/D
      exchange kinetics may not directly reflect ion structures.

PMID- 15149248
TI  - Underlying processes in the implicit association test: dissociating salience from
      associations.
AB  - The authors investigated whether effects of the Implicit Association Test (IAT)
      are influenced by salience asymmetries, independent of associations. Two series
      of experiments analyzed unique effects of salience by using nonassociated,
      neutral categories that differed in salience. In a 3rd series, salience
      asymmetries were manipulated experimentally while holding associations between
      categories constant. In a 4th series, valent associations of the target
      categories were manipulated experimentally while holding salience asymmetries
      constant. Throughout, IAT effects were found to depend on salience asymmetries.
      Additionally, salience asymmetries between categories were assessed directly with
      a visual search task to provide an independent criterion of salience asymmetries.
      Salience asymmetries corresponded to IAT effects and also accounted for common
      variance in IAT effects and explicit measures of attitudes or the self-concept.

PMID- 15149249
TI  - Induction and categorization in young children: a similarity-based model.
AB  - The authors present a similarity-based model of induction and categorization in
      young children (SINC). The model suggests that (a). linguistic labels contribute
      to the perceived similarity of compared entities and (b). categorization and
      induction are a function of similarity computed over perceptual information and
      linguistic labels. The model also predicts young children's similarity judgment,
      induction, and categorization performance under different stimuli and task
      conditions. Predictions of the model were tested and confirmed in 6 experiments,
      in which 4- to 5-year-olds performed similarity judgment, induction, and
      categorization tasks using artificial and real labels (Experiments 1-4) and
      recognition memory tasks (Experiments 5A and 5B). Results corroborate the
      similarity-based account of young children's induction and categorization, and
      they support both qualitative and quantitative predictions of the model.

PMID- 15149250
TI  - The generality of working memory capacity: a latent-variable approach to verbal
      and visuospatial memory span and reasoning.
AB  - A latent-variable study examined whether verbal and visuospatial working memory
      (WM) capacity measures reflect a primarily domain-general construct by testing
      236 participants in 3 span tests each of verbal WM. visuospatial WM, verbal short
      term memory (STM), and visuospatial STM. as well as in tests of verbal and
      spatial reasoning and general fluid intelligence (Gf). Confirmatory' factor
      analyses and structural equation models indicated that the WM tasks largely
      reflected a domain-general factor, whereas STM tasks, based on the same stimuli
      as the WM tasks, were much more domain specific. The WM construct was a strong
      predictor of Gf and a weaker predictor of domain-specific reasoning, and the
      reverse was true for the STM construct. The findings support a domain-general
      view of WM capacity, in which executive-attention processes drive the broad
      predictive utility of WM span measures, and domain-specific storage and rehearsal
      processes relate more strongly to domain-specific aspects of complex cognition.

PMID- 15149251
TI  - Working memory, task switching, and executive control in the task span procedure.
AB  - Four experiments explored the task span procedure: Subjects received lists of 1
      10 task names to remember and then lists of 1-10 stimuli on which to perform the
      tasks. Task span is the number of tasks performed in order perfectly. Experiment
      1 compared the task span with the traditional memory span in 6 practiced subjects
      and found little difference. Experiment 2 compared the task span and the memory
      span in 64 unpracticed subjects and also found little difference. Experiment 3
      compared practice with consistent and varied lists to address retrieval from long
      term memory. Experiment 4 manipulated the number of task switches and found that
      it had little effect on task spans. The results suggest there is no trade-off
      between storage and task switching, which supports some theories of executive
      control and challenges others.

PMID- 15149252
TI  - Effects of subclinical depression and aging on generative reasoning about linear
      orders: same or different processing limitations?
AB  - The performance of older adults and depressed people on linear order reasoning is
      hypothesized to be best explained by different theoretical models. Whereas
      depressed younger adults are found to be impaired in generative inference making,
      older adults are well capable of making such inferences but exhibit problems with
      working memory (Experiments 1 and 2). Restriction of the available study time
      impairs reasoning by nondepressed control participants and. as such, proves to be
      a good model of older adults' but not depressed participants' limitations
      (Experiment 3). These results are replicated comparing depressed and older
      participants with a control group in the same study, providing increased power
      and linking the results to additional control measures of processing speed and
      working memory (Experiment 4).

PMID- 15149253
TI  - On the locus of speed-accuracy trade-off in reaction time: inferences from the
      lateralized readiness potential.
AB  - Lateralized readiness potentials (LRPs) were used to determine the stage(s) of
      reaction time (RT) responsible for speed-accuracy trade-offs (SATs). Speeded
      decisions based on several types of information were examined in 3 experiments,
      involving, respectively, a line discrimination task, lexical decisions, and an
      Erikson flanker task. Three levels of SAT were obtained in each experiment by
      adjusting response deadlines with an adaptive tracking algorithm. Speed stress
      affected the duration of RT stages both before and after the start of the LRP in
      all experiments. The latter effect cannot be explained by guessing strategies, by
      variations in response force, or as an indirect consequence of the pre-LRP
      effect. Contrary to most models, it suggests that SAT can occur at a late
      postdecisional stage.

PMID- 15149254
TI  - Visual word recognition of single-syllable words.
AB  - Speeded visual word naming and lexical decision performance are reported for 2428
      words for young adults and healthy older adults. Hierarchical regression
      techniques were used to investigate the unique predictive variance of
      phonological features in the onsets, lexical variables (e.g., measures of
      consistency, frequency, familiarity, neighborhood size, and length), and semantic
      variables (e.g. imageahility and semantic connectivity). The influence of most
      variables was highly task dependent, with the results shedding light on recent
      empirical controversies in the available word recognition literature. Semantic
      level variables accounted for unique variance in both speeded naming and lexical
      decision performance, level with the latter task producing the largest semantic
      level effects. Discussion focuses on the utility of large-scale regression
      studies in providing a complementary approach to the standard factorial designs
      to investigate visual word recognition.

PMID- 15149255
TI  - The pros and cons of temporally near and distant action.
AB  - The present research demonstrated that in considering an action, considerations
      against (con) the action tend to be subordinate to considerations in favor of
      (pro) the action in that cons are considered only if the level of pros is
      sufficient, whereas pros are considered independent of the level of cons (Studies
      1A and IB). The authors therefore concluded that pros constitute a higher
      construal level than cons and predict, on the basis of temporal construal
      processes (Y. Trope & N. Liberman. 2003). that pros would be more salient in
      making decisions for the more distant future, whereas the reverse should hold for
      cons. As predicted, participants generated more pros and fewer cons toward new
      exam procedures (Study 2), public policies (Study 3), and personal and
      interpersonal behaviors (Studies 4-6) that were expected to take place in the
      more distant future. This research also examined the limiting conditions and the
      evaluative consequences of these shifts.

PMID- 15149256
TI  - The social cognition of immigrants' acculturation: effects of the need for
      closure and the reference group at entry.
AB  - Three studies found support for the notion that immigrants' acculturation to the
      host culture is interactively determined by their need for cognitive closure (A.
      W. Kruglanski & D. M. Webster, 1996) and the reference group they forge on their
      arrival. If such reference group is fashioned by close social relations with
      coethnics, the higher the immigrants' need for closure, the weaker their tendency
      to assimilate to the new culture and the stronger their tendency to adhere to the
      culture of origin. By contrast, if the reference entry group is fashioned by
      close relations with members of the host country, the higher their need for
      closure, the stronger their tendency to adapt to the new culture and the weaker
      their tendency to maintain the culture of origin. These findings obtained
      consistently across 3 immigrant samples in Italy, 1 Croatian and 2 Polish, and
      across multiple different measures of acculturation.

PMID- 15149257
TI  - The redux of cognitive consistency theories: evidence judgments by constraint
      satisfaction.
AB  - The authors suggest that decisions made from multiple pieces of evidence are
      performed hy mechanisms of parallel constraint satisfaction, which are related to
      cognitive consistency theories. Such reasoning processes are bidirectional-
      decisions follow from evidence, and evaluations of the evidence shift toward
      coherence with the emerging decision. Using a factually complex legal case, the
      authors observed patterns of coherence shifts that persisted even when the
      distribution of decisions was manipulated (Study 1) and influenced by the
      participants' attitudes (Study 2). The evaluations of the evidence cohered with
      the preferred decision even when participants changed their preference (Study 3).
      Supporting the bidirectionality of reasoning. Study 4 showed that assigning
      participants to a verdict affected their evaluation of the evidence. Coherence
      shifts were observed also in related background knowledge. This research suggests
      that cognitive consistency theories should play a greater role in the
      understanding of human reasoning and decision making.

PMID- 15149258
TI  - Vicarious agency: experiencing control over the movements of others.
AB  - Participants watched themselves in a mirror while another person behind them,
      hidden from view, extended hands forward on each side where participants' hands
      would normally appear. The hands performed a series of movements. When
      participants could hear instructions previewing each movement, they reported an
      enhanced feeling of controlling the hands. Hearing instructions for the movements
      also enhanced skin conductance responses when a rubber band was snapped on the
      other's wrist after the movements. Such vicarious agency was not felt when the
      instructions followed the movements, and participants' own covet movement mimicry
      was not essential to the influence of previews on reported control.

PMID- 15149259
TI  - The effects of cooperation and competition on intrinsic motivation and
      performance.
AB  - The authors examined the effects of competition and cooperation on intrinsic
      motivation and performance in 4 studies. Across 3 behavioral studies that
      involved shooting a basketball, no differences were observed between competition
      and cooperation on task enjoyment or performance. However, the combination of
      competition and cooperation (intergroup competition) consistently led to higher
      levels of intrinsic motivation, and in 2 of the 3 studies, performance. In a
      questionnaire study, the authors replicated the positive effects of intergroup
      competition on enjoyment and examined process measures that might account for
      these effects. These findings suggest that competition and cooperation both have
      positive aspects and that structuring recreational activities to include both can
      facilitate high levels of both intrinsic motivation and performance.

PMID- 15149260
TI  - Intergroup distinctiveness and differentiation: a meta-analytic integration.
AB  - The authors examined the relation between perceptions of intergroup
      distinctiveness and intergroup differentiation in a meta-analysis. They tested
      the social identity theory prediction that low intergroup distinctiveness
      underlies differentiation (the "reactive distinctiveness" hypothesis) for effects
      on behavioral and judgmental differentiation. In addition, they examined the
      moderating power of 4 variables that H. Tajfel and J. C. Turner (1979) predicted
      would influence differentiation (group identification, relevance of the dimension
      of comparison, relevance of the outgroup. and nature of intergroup relations).
      Analysis of 60 tests revealed that the overall effect of distinctiveness on
      differentiation was not significantly different from 0, but reactive
      distinctiveness was found on behavioral differentiation measures, whereas
      reflective distinctiveness was found on judgmental differentiation measures. Only
      group identification was a reliable moderator. High identifiers showed reactive
      distinctiveness, whereas low identifiers showed reflective distinctiveness.

PMID- 15149261
TI  - Flux, pulse, and spin: dynamic additions to the personality lexicon.
AB  - Personality constructs were proposed to describe intraindividual variability in
      interpersonal behavior. Flux refers to variability about an individual's mean
      score on an interpersonal dimension and was examined for the 4 poles of the
      interpersonal circumplex. Pulse and spin refer to variability about an
      individual's mean extremity and mean angular coordinate on the interpersonal
      circumplex. These constructs were measured using event-contingent recording.
      Latent state-trait analyses indicated high stability of flux in submissive,
      agreeable, and quarrelsome behaviors and some stability in the flux of dominance.
      Further analyses indicated moderate to high stability in pulse and spin.
      Neuroticism predicted greater pulse, spin, and submissive behavior flux.
      Extraversion predicted greater flux in agreeable behavior. In contrast,
      Agreeableness predicted reduced spin and quarrelsome behavior flux. Social
      environmental variables predicted greater flux in dominant behavior. Flux, pulse,
      and spin provide reliable and distinctive additions to the vocabulary for
      describing individual differences.

PMID- 15149262
TI  - Realism, instrumentalism, and scientific symbiosis: psychological theory as a
      search for truth and the discovery of solutions.
AB  - Scientific realism holds that scientific theories are approximations of universal
      truths about reality, whereas scientific instrumentalism posits that scientific
      theories are intellectual structures that provide adequate predictions of what is
      observed and useful frameworks for answering questions and solving problems in a
      given domain. These philosophical perspectives have different strengths and
      weaknesses and have been regarded as incommensurate: Scientific realism fosters
      theoretical rigor, verifiability, parsimony, and debate, whereas scientific
      instrumentalism fosters theoretical innovation, synthesis, generativeness, and
      scope. The authors review the evolution of scientific realism and instrumentalism
      in psychology and propose that the categorical distinction between the 2 is
      overstated as a prescription for scientific practice. The authors propose that
      the iterative deployment of these 2 perspectives, just as the iterative
      application of inductive and deductive reasoning in science, may promote more
      rigorous, integrative, cumulative, and useful scientific theories.

PMID- 15149263
TI  - Relapse prevention for alcohol and drug problems: that was Zen, this is Tao.
AB  - Relapse prevention, based on the cognitive-behavioral model of relapse, has
      become an adjunct to the treatment of numerous psychological problems, including
      (but not limited to) substance abuse, depression, sexual offending, and
      schizophrenia. This article provides an overview of the efficacy and
      effectiveness of relapse prevention in the treatment of addictive disorders, an
      update on recent empirical support for the elements of the cognitive-behavioral
      model of relapse, and a review of the criticisms of relapse prevention. In
      response to the criticisms, a reconceptualized cognitive-behavioral model of
      relapse that focuses on the dynamic interactions between multiple risk factors
      and situational determinants is proposed. Empirical support for this
      reconceptualization of relapse, the future of relapse prevention, and the
      limitations of the new model are discussed.

PMID- 15149264
TI  - Guidelines for psychological practice with older adults.

PMID- 15149272
TI  - How universal is the big-fish-little-pond effect?

PMID- 15149273
TI  - It's not how the pond makes you feel, but rather how high you can jump.

PMID- 15149275
TI  - Where is Kuhn going?

PMID- 15149276
TI  - Approaching psychological science with Kuhn's eyes.

PMID- 15149277
TI  - The disunity-unity dimension.

PMID- 15149278
TI  - Sources of comfort and change in this "would-be" science.
AB  - Responds to comments made by numerous authors (see records 2004-14303-014, 2004
      14303-015, and 2004-14303-016) on the current author's original article (see
      record 2003-05602-002), which presented an account of why psychologists have
      almost continuously invoked Kuhn since the 1970s to justify a wide array of the
      discipline's historical developments and epistemological proclivities. ((c) 2004
      APA, all rights reserved)

PMID- 15149279
TI  - Old wine in a slightly cracked new bottle.

PMID- 15149282
TI  - Effects of pro- and anti-inflammatory cytokines and nitric oxide donors on
      hyaluronic acid synthesis by synovial cells from patients with rheumatoid
      arthritis.
AB  - The aim of the present study was to investigate the effects of (i) the pro
      inflammatory cytokines IL (interleukin)-1beta, TNF-alpha (tumour necrosis factor
      alpha), IFN-gamma (interferon-gamma) and anti-inflammatory cytokines IL-4 and IL
      13, and (ii) NO (nitric oxide) donors on HA (hyaluronic acid) production by
      synovial cells from patients with rheumatoid arthritis. Synovial cells obtained
      from five patients with rheumatoid arthritis were incubated for 24 h without or
      with IL-1beta, TNF-alpha, IFN-gamma, or with this mixture for 24 h plus IL-4 or
      IL-13 for the last 6 h. The same cells were also incubated for 3-24 h without or
      with SNP (sodium nitroprusside) or SNAP (S-nitroso-N-acetyl-DL-penicillamine). HA
      secretion was determined by an immunoenzymic assay based on HA-specific binding
      by proteoglycan isolated from bovine cartilage. IL-1beta, TNF-alpha and IFN-gamma
      alone or in combination stimulated HA synthesis, whereas IL-4 and IL-13 dose
      dependently inhibited HA production induced by Th1 cytokines. HA production was
      significantly increased by the presence of 1 mM SNP after 6 and 12 h (maximal
      effect). HA production was significantly increased by the presence of 0.01 and
      0.1 mM SNAP after 12 h of incubation, and cells treated with 1 mM SNAP showed a
      maximal HA production after 24 h of incubation. In conclusion, the present study
      provides data concerning the regulatory role of pro- and anti-inflammatory
      cytokines and NO donors on HA metabolism in rheumatoid synovial cells and may
      help in understanding the pathophysiology of rheumatoid arthritis.

PMID- 15149283
TI  - Characterization of a sterol carrier protein 2/3-oxoacyl-CoA thiolase from the
      cotton leafworm (Spodoptera littoralis): a lepidopteran mechanism closer to that
      in mammals than that in dipterans.
AB  - Numerous invertebrate species belonging to several phyla cannot synthesize
      sterols de novo and rely on a dietary source of the compound. SCPx (sterol
      carrier protein 2/3-oxoacyl-CoA thiolase) is a protein involved in the
      trafficking of sterols and oxidation of branched-chain fatty acids. We have
      isolated SCPx protein from Spodoptera littoralis (cotton leafworm) and have
      subjected it to limited amino acid sequencing. A reverse-transcriptase PCR-based
      approach has been used to clone the cDNA (1.9 kb), which encodes a 57 kDa
      protein. Northern blotting detected two mRNA transcripts, one of 1.9 kb, encoding
      SCPx, and one of 0.95 kb, presumably encoding SCP2 (sterol carrier protein 2).
      The former mRNA was highly expressed in midgut and Malpighian tubules during the
      last larval instar. Furthermore, constitutive expression of the gene was detected
      in the prothoracic glands, which are the main tissue producing the insect
      moulting hormone. There was no significant change in the 1.9 kb mRNA in midgut
      throughout development, but slightly higher expression in the early stages.
      Conceptual translation of the cDNA and a database search revealed that the gene
      includes the SCP2 sequence and a putative peroxisomal targeting signal in the C
      terminal region. Also a cysteine residue at the putative active site for the 3
      oxoacyl-CoA thiolase is conserved. Southern blotting showed that SCPx is likely
      to be encoded by a single-copy gene. The mRNA expression pattern and the gene
      structure suggest that SCPx from S. littoralis (a lepidopteran) is evolutionarily
      closer to that of mammals than to that of dipterans.

PMID- 15149286
TI  - Treatment with intravenous hyperalimentation for severely anorectic patients and
      its outcome.
AB  - In treating patients with severe anorexia nervosa, it is important to improve
      their physical condition first. Patients who had lost close to 60% standard
      bodyweight (SBW) were candidates for inpatient treatment due to the mortality
      risk. With 80% SBW as the target for therapy, they were given both intravenous
      hyperalimentation and food by oral intake in order to improve their physical
      condition. In total, 51 patients were admitted. One died and four patients
      dropped out in the course of treatment. Forty-six patients who completed the
      inpatient treatment were reviewed. Although admitted with an average weight of
      approximately 60% SBW, they were discharged with a weight of approximately 80%
      SBW after approximately 60 days. An average follow up of 25.0 months was
      conducted, and two patients were found to have died. The mean weight, percentage
      resuming menstruation, and rehospitalization rate of the 44 survivors were 79%
      SBW, 23%, and 32%, respectively. The patients with the restricting type of
      anorexia had an earlier onset of the disorder and a better social outcome.
      Patients in whom onset occurred at a younger age had a better social outcome.
      After being discharged, the majority of the patients continued treatment as
      outpatients. Although the results were similar to those of conventional studies
      in terms of outcome, the shorter hospitalization was significant. Overall, in the
      treatment of patients with severe anorexia nervosa, it is important to begin
      psychotherapy while trying to improve their physical condition.

PMID- 15149284
TI  - Transketolase from Leishmania mexicana has a dual subcellular localization.
AB  - Transketolase has been characterized in Leishmania mexicana. A gene encoding this
      enzyme was identified and cloned. The gene was expressed in Escherichia coli and
      the protein was purified and characterized. An apparent K(m) of 2.75 mM for
      ribose 5-phosphate was determined. X-ray crystallography was used to determine
      the three-dimensional structure of the enzyme to a resolution of 2.2 A (1 A
      identical with 0.1 nm). The C-terminus of the protein contains a type-1
      peroxisome-targeting signal, suggestive of a possible glycosomal subcellular
      localization. Subcellular localization experiments performed with promastigote
      forms of the parasite revealed that the protein was predominantly cytosolic,
      although a significant component of the total activity was associated with the
      glycosomes. Transketolase is thus the first enzyme of the nonoxidative branch of
      the pentose phosphate pathway whose presence has been demonstrated in a
      peroxisome-like organelle.

PMID- 15149287
TI  - Human leukocyte antigen-DQB1 alleles are not associated with schizophrenia in
      Kuwaiti Arabs.
AB  - Schizophrenia is among the most severe and debilitating of psychiatric disorders
      and has a complex mode of inheritance. A susceptibility locus has been identified
      on chromosome 6 and some association studies involving human leukocyte antigen
      (HLA) genes have reported diverse results. The objective of the present study was
      to determine if there is an association between HLA-DQB1 alleles and
      schizophrenia in Kuwaiti Arabs. The frequency of HLA-DQB1 alleles was determined
      in a cohort of 195 Kuwaiti Arabs consisting of 81 schizophrenia patients and 114
      ethnically matched healthy controls, using a polymerase chain reaction-sequence
      specific primers method. A total of nine DQB1 alleles were identified in this
      Kuwaiti cohort. The most prevalent DQB1 alleles in Kuwaiti schizophrenia patients
      were *0601 (28%), *0201 (23%) and *0501 (16%), respectively. However, no
      significant difference in the allele frequency was detected between schizophrenia
      patients and the controls. The DQB1*0602 allele, which has been negatively
      associated in African-Americans in previous reports, was not detected in the
      present Kuwaiti schizophrenia patients or controls.

PMID- 15149285
TI  - Structure and cholesterol domain dynamics of an enriched caveolae/raft isolate.
AB  - Despite the importance of cholesterol in the formation and function of caveolar
      microdomains in plasma membranes, almost nothing is known regarding the
      structural properties, cholesterol dynamics or intracellular factors affecting
      caveolar cholesterol dynamics. A non-detergent method was employed to isolate
      caveolae/raft domains from purified plasma membranes of murine fibroblasts. A
      series of fluorescent lipid probe molecules or a fluorescent cholesterol
      analogue, dehydroergosterol, were then incorporated into the caveolae/raft
      domains to show that: (i) fluorescence polarization of the multiple probe
      molecules [diphenylhexatriene analogues, DiI18 (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate), parinaric acids and NBD-stearic acid
      [12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-octadecanoic acid]
      indicated that acyl chains in caveolae/raft domains were significantly less
      'fluid' (i.e. more rigid) and the transbilayer 'fluidity gradient' was 4.4-fold
      greater than in plasma membranes; (ii) although sterol was more ordered in
      caveolae/raft domains than plasma membranes, spontaneous sterol transfer from
      caveolae/raft domains was faster (initial rate, 32%; half-time, t(1/2), 57%) than
      from the plasma membrane; (iii) although kinetic analysis showed similar
      proportions of exchangeable and non-exchangeable sterol pools in caveolae/raft
      domains and plasma membranes, addition of SCP-2 (sterol carrier protein-2) 1.3
      fold more selectively increased sterol transfer from caveolae/raft domains by
      decreasing the t(1/2) (50%) and increasing the initial rate (5-fold); (iv) SCP-2
      was also 2-fold more selective in decreasing the amount of non-exchangeable
      sterol in caveolae/raft domains compared with plasma membranes, such that nearly
      80% of caveolar/raft sterol became exchangeable. In summary, although
      caveolae/raft lipids were less fluid than those of plasma membranes, sterol
      domains in caveolae/rafts were more spontaneously exchangeable and more affected
      by SCP-2 than those of the bulk plasma membranes. Thus caveolae/raft domains
      isolated without the use of detergents display unique structure, cholesterol
      domain kinetics and responsiveness to SCP-2 as compared with the parent plasma
      membrane.

PMID- 15149288
TI  - Trait and state aspects of harm avoidance and its implication for treatment in
      major depressive disorder, dysthymic disorder, and depressive personality
      disorder.
AB  - The authors evaluated the trait/state issues of harm avoidance in depressive
      spectrum disorders and its predictive potential for antidepressant response.
      Subjects with Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM
      IV) major depressive disorder (n = 39), dysthymic disorder (n = 37), depressive
      personality disorder (n = 39), and healthy control subjects (n = 40) were
      evaluated with the Temperament and Character Inventory and the 17-item Hamilton
      Depression Rating Scale (HDRS-17) at baseline and after a 12 week antidepressant
      treatment period. Higher harm avoidance scores predicted lesser improvement in
      subjects with dysthymic disorder and major depressive disorder, as determined by
      lesser decrease in HDRS-17 scores. Mean harm avoidance scores in depressed
      subjects were consistently greater than those in healthy controls, controlling
      for age, gender and diagnosis. Mean harm avoidance scores decreased significantly
      in all depressive-spectrum disorders after treatment, but still remained higher
      than harm avoidance scores in control subjects. The present study reports that
      harm avoidance is a reliable predictor of antidepressant treatment in subjects
      with major depressive disorder and dysthymic disorder and that harm avoidance is
      both trait- and state-dependent in depressive-spectrum disorders.

PMID- 15149289
TI  - Attention disorders in schizophrenia.
AB  - In order to clarify the feature of attention disorders in schizophrenia, two
      tasks (X and AX) of the Continuous Performance Test (CPT) were given to 36
      schizophrenic patients and 25 healthy controls. The schizophrenic patients
      performed considerably less well than normal controls. Performances were
      expressed in indices such as omission and commission errors, reaction time and
      discriminability. Among errors, omission in both the X and AX tasks was found to
      be an index that varied in reaction time, indicating difficulty in sustaining
      attention. Omission was found to act as a state-dependent index of schizophrenia
      in relation to inattentiveness in clinical settings and emotional disturbance in
      interpersonal situations. Commission, in contrast, differed between the two
      tasks, acting as an index of disinhibition of reaction in the X task, and of
      disturbance of the capacity and allocation of attention in the AX task.
      Commission was also thought to be an index related to thought disorder during
      episodes of acute schizophrenia, that is, it reflects an essential pathology in
      schizophrenia.

PMID- 15149290
TI  - Role and attitude of companions on geriatric psychiatry outpatient visits in
      Taiwan.
AB  - The purpose of the present paper was to investigate the role and attitude of
      people who accompanied geriatric patients to an outpatient psychiatric clinic.
      The study was conducted at a large university hospital in Taiwan. Participants
      included 108 patients aged 65 years and older who were seen for their initial
      psychiatric visit; 81 patients were accompanied. All accompanying people were
      interviewed to obtain their assumed role and attitude during the visit. Data were
      gathered prospectively; statistical analyses were performed using SPSS-PC.
      Accompanied patients (75% of participants) were older than those in the
      unaccompanied group. Most patients (53.1%) were accompanied by adult children who
      lived with them. Of the accompanying spouses, 48% were described as a supporter,
      and 60% showed a positive attitude. Most of the accompanying children acted as
      critics and speakers. Accompanying people whose responsible patients reported
      insomnia and suicide attempts showed a significantly positive attitude, whereas
      people who accompanied alcoholic patients were more negative and assumed a critic
      role. Many accompanying people requested further examination and drug treatment
      and expressed concern that the patient may be mentally ill. The role and attitude
      of accompanying people on the geriatric patient encounter are important factors
      in promoting patient-doctor communication and trust.

PMID- 15149291
TI  - Phosphorylation of ERK and CREB in cultured hippocampal neurons after haloperidol
      and risperidone administration.
AB  - The purpose of the present paper was to determine whether the brief exposure of
      neurons to antipsychotic drugs is associated with the activation of extracellular
      signal-regulated kinases (ERK) and cyclic adenosine 3',5'-monophosphate (cAMP)
      response element (CRE) binding protein (CREB). The activation of ERK-1/2 and CREB
      can be monitored by immunoblotting with antibodies that specifically recognize p
      ERK-1/2 (phosphorylated on Thr-202 and Tyr-204) and p-CREB (phosphorylated on Ser
      133). In hippocampal neuron cultures at 25 days in vitro (DIV), the levels of ERK
      and CREB phosphorylation significantly increased after treatment with haloperidol
      (50 nmol/L) and risperidone (50 nmol/L), except when risperidone was administered
      at the p-CREB level. However, risperidone also increased the p-CREB level at an
      insignificant rate in the same direction. At 10 DIV, none of the antipsychotic
      drugs significantly increased the level of ERK and CREB phosphorylation. The
      difference between levels of ERK and CREB phosphorylation in response to
      haloperidol and risperidone at 25 DIV was also observed. Risperidone
      significantly increased the level of ERK-1/2 phosphorylation, but not the level
      of CREB phosphorylation. Haloperidol, in contrast, had a different effect. These
      data indicate that neuronal maturation affects the phosphorylation of ERK and
      CREB in response to antipsychotic drugs. Furthermore, these results demonstrate
      that different antipsychotic drugs could lead to different profiles of ERK and
      CREB phosphorylation in neurons.

PMID- 15149292
TI  - Differences of satisfaction with medication between patients with schizophrenia
      treated with typical antipsychotics and atypical antipsychotics.
AB  - Many studies have demonstrated that atypical antipsychotics are superior to
      typical antipsychotics in that they have fewer side-effects and produce better
      improvement of cognitive deficits and quality of life in patients with
      schizophrenia. However, most of these studies dealt with objective indices
      assessed by researchers rather than subjective indices that are indeed important
      to patients themselves. In 126 patients with schizophrenia, annoyance of side
      effects and psychotic symptoms, satisfaction with medication, wish to change
      medication, and knowledge of atypical antipsychotics were assessed using
      questionnaires. Patients treated with typical antipsychotics complained less of
      annoyance of poor attention and concentration than those treated with atypical
      antipsychotics, which can be explained by increased awareness of these symptoms
      by the patients due to the improvement of cognitive function. There were no
      significant differences between the two groups in other variables. The present
      results that satisfaction and annoyance were similar between patients treated
      with typical antipsychotics and those with atypical antipsychotics, may partly
      explain why patients hesitated and rejected changing or shifting from typical to
      atypical antipsychotics. But because 98 of 126 patients did not know about
      atypical antipsychotics, it is important to educate the patients on the merits of
      atypical antipsychotics.

PMID- 15149294
TI  - Special reference to employee knowledge about depression and suicide: baseline
      results of a workplace-based mental health support program.
AB  - With the sustained economic recession, suicide has been increasing in Japan (more
      than 300000 victims annually since 1998), particularly among middle-aged
      employees. Development of preventive measures is needed; however, employees have
      limited knowledge of the basic information about depression and suicide. One
      office in Saitama Prefecture, Japan, has been provided with a mental health
      support program. An initial questionnaire survey was conducted in December 1999.
      It contained demographic data and information about working styles and daily
      habits, including alcohol and tobacco use, quality of sleep, social support, the
      general well-being schedule, and knowledge/attitude toward depression and
      suicide. Of 225 eligible people, 216 men and women participated. Most of them had
      stressful schedules and demanding jobs. Their subjective well-being was generally
      poorer relative to the reference. The mean score of knowledge was 10.5 (SD =
      2.02) for 14 items. The accuracy rates ranged from 97.6% incorrect (false) for
      such items as 'Most suicide victims consult psychiatrists before their deaths' to
      42.1% correct (true) for 'A suicidal individual tends to be accident-prone for
      traffic accidents and injuries.' One-fourth of them had unfavorable attitudes
      toward depressive colleagues. Neither age nor gender was related to knowledge
      level and attitude. Variations were observed in the knowledge that employees had
      toward depression and suicide. A program that provides employees with appropriate
      information related to mental health is needed.

PMID- 15149293
TI  - Neurological soft signs in schizophrenic patients with obsessive-compulsive
      disorder.
AB  - The purpose of this study was to examine neurological soft signs (NSS) in
      schizophrenic patients with obsessive-compulsive disorder (OCD). Neurological
      soft signs were assessed in 15 schizophrenic patients with OCD (OCD
      schizophrenia), 38 schizophrenia patients without OCD (non-OCD-schizophrenia),
      and 24 healthy controls (HC) by means of the Neurological Evaluation Scale (NES).
      The OCD-schizophrenia group had significantly higher scores on total and
      subscales of 'sensory integration' and 'others' of NES than the HC group.
      Subscale scores of 'sequencing of motor acts' in-non-OCD-schizophrenia patients
      were significantly higher compared to OCD-schizophrenia patients. Total NES
      scores of both groups were significantly correlated with Scale for the Assessment
      of Negative Symptoms (SANS) scores. Only the subscale of 'sequencing of motor
      acts' was significantly correlated with SANS within the OCD-schizophrenia group.
      These results suggest that NSS do not significantly differ between schizophrenia
      patients with and without OCD, contrary to expectations. The NES scores in OCD
      schizophrenic patients do not appear to be related to a more severe form of
      schizophrenia. Neurological signs and negative symptoms in schizophrenia patients
      with and without OCD may be considered as neurodevelopmental predisposing
      factors. Further research is required in schizophrenia patients with OCD to
      investigate the relationships between NSS and several neuroimaging or
      neuropsychological findings, constituting a subgroup within the schizophrenia
      spectrum.

PMID- 15149295
TI  - Defense styles in depressed suicide attempters.
AB  - Defense styles may discriminate between depressed patients with or without recent
      suicide attempts. The aim of the present study was to identify which defense
      mechanisms are associated with recent suicide attempts in depression. The Defense
      Style Questionnaire (DSQ) was rated at admission by 156 depressed inpatients with
      (n = 60) or without (n = 96) recent suicide attempt. Depression intensity was
      correlated negatively with mature style, humor and sublimation and positively
      with projection. Although it was not significantly different in terms of
      sociodemographic and depression variables, recent suicide attempters had higher
      scores on immature style, especially acting out, passive agression, autistic
      fantasy and projection. Prospective assessment of defense styles and suicide
      attempts should be carried out to determine whether these differences are a cause
      of imminent suicide attempts in depression. If so, the DSQ may be used in
      clinical practice to help discriminate depressed patients with high risk of
      imminent suicide attempt.

PMID- 15149296
TI  - Intra-episode hypomanic symptoms during major depression and their correlates.
AB  - Recent studies have shown that 40-50% of major depressive disorders (MDD) may
      become bipolar with time. Intra-episode hypomanic symptoms in MDD may be a first
      step in this shift. The purpose of the present study was to find factors
      associated with intra-episode hypomanic symptoms in MDD. Two hundred and forty
      three consecutive MDD outpatients were interviewed with the Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM
      IV), Clinician Version (SCID-CV), as modified by Benazzi and Akiskal (J. Affect.
      Disord. 2003; 73: 33-38). History of hypomania and presence of hypomanic symptoms
      during major depressive episode (MDE) were systematically assessed. Intra-episode
      hypomanic symptoms were defined as an MDE combined with three or more hypomanic
      symptoms, following Akiskal and Benazzi (J. Affect. Disord. 2003; 73: 113-122).
      Major depressive disorder with intra-episode hypomanic symptoms (MDD + H) was
      compared to MDD without hypomanic symptoms on classic bipolar validators. It was
      found that MDD + H (usually irritability, distractibility, racing thoughts,
      psychomotor agitation, and more talkativeness) was present in 32.5% of patients.
      Patients with MDD + H versus MDD had significantly lower age at onset, more
      atypical depressions, and more bipolar family history. Recurrences were not
      significantly different. Multivariate logistic regression found that bipolar
      family history and atypical depression were significantly and independently
      associated with MDD + H. Findings suggest that MDD + H may be associated with a
      bipolar vulnerability. Duration of illness and recurrences do not seem to be
      important for the onset of MDD + H. Bipolar genetic vulnerability seems to be
      required for onset of intra-episode hypomanic symptoms in MDD. Intra-episode
      hypomanic symptoms might be the first step of a process leading to the switch of
      MDD to bipolar disorders. Predicting the switch might have important treatment
      implications, because antidepressants used alone may worsen the course of bipolar
      disorders. Prospective studies are required to support these findings and
      hypotheses.

PMID- 15149297
TI  - Lipid and lipoprotein levels in depressive disorders with melancholic feature or
      atypical feature and dysthymia.
AB  - The purpose of the present study was to explore the relationship between serum
      lipid and lipoprotein levels and clinical subtypes in patients with depressive
      disorders. A total of 207 patients who were admitted for general health screening
      were assessed by using the semistructured clinical interview for Diagnostic and
      Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for the
      possibility of having depressive disorders. Blood and physical examinations were
      done to rule out systemic diseases. A total of 142 patients without systemic
      diseases was recruited for further analysis, including dysthymia (n = 35), major
      depressive disorder with melancholic feature (n = 22), major depressive disorder
      with atypical feature (n = 46) and normal controls (n = 39). Analysis of
      covariance after age adjustment reveals significant differences in patients with
      melancholic feature and patients with atypical feature in serum concentrations of
      triglyceride (TG) and very-low-density-lipoprotein cholesterol (VLDL) in men, and
      high-density-lipoprotein cholesterol (HDL) in women. This suggests that the TG,
      VLDL and HDL levels might be used as biological markers to differentiate between
      major depressive patients with melancholic feature or atypical feature.

PMID- 15149298
TI  - Electrogastrography abnormality in eating disorders.
AB  - Eating disorders are common psychiatric disorders in young women. The aim of the
      present study was to evaluate the gastric electrical activity of patients with
      eating disorders and its relation to their symptoms. The electrogastrography
      (EGG) was performed before and after a water load test for outpatients with
      eating disorders (n = 36; 14 anorexia nervosa, 14 bulimia nervosa, eight eating
      disorder not otherwise specified) and healthy women (n = 19). A structured
      interview (Eating Disorder Examination) was used to assess clinical symptoms. The
      percentage of normal gastric myoelectrical power was significantly smaller in the
      eating disorder patients (44.5% vs 74.2%; P < 0.05), while the percentage of
      bradygastric power was significantly greater, both before and after the water
      load test compared with the control subjects (30.4% vs 10.4%; P < 0.05). In
      addition, moderate correlation was found between the duration of illness and the
      percentage of bradygastria (P < 0.05). In conclusion, it is suggested that
      longstanding abnormal eating in patients with eating disorders may induce
      disturbances to gastric motor function, resulting in their abnormal, eating
      related behavior, and form a symptomatic vicious circle. The EGG may be a
      promising method for determining the pathophysiology of eating disorders and for
      developing effective therapeutic approaches.

PMID- 15149299
TI  - Quality of life and its correlates in patients with bipolar disorder stabilized
      on lithium prophylaxis.
AB  - The quality of life (QOL) of 50 bipolar disorder patients in remission
      (stabilized on lithium prophylaxis) was assessed and compared with that of
      clinically stable patients with schizophrenia (n = 20) and healthy subjects (n =
      20). World Health Organization Quality of Life-Bref (WHOQOL-BREF) and Quality of
      Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to assess QOL
      in the three groups of subjects. The factors that contribute or influence QOL
      (i.e. stressful life events, social support, daily hassles) were also studied
      using standardized instruments in the study group. It was found that, compared to
      schizophrenia group, the bipolar group had significantly better QOL in all the
      domains of Q-LES-Q and the domains of general well-being, physical health and
      psychological health of the WHOQOL-Bref. The bipolar group had similar QOL scores
      in all other domains and higher scores in leisure time activity domain of Q-LES
      Q, in comparison to the healthy group. The QOL in the bipolar group was better in
      patients who were younger and had a lesser severity of daily hassle. The present
      findings suggest that euthymic patients with bipolar disorder have a QOL that is
      comparable to that of healthy subjects. In contrast, patients with clinically
      stable schizophrenia have a poorer QOL. Occurrence of daily hassles contributes
      significantly to QOL in patients with bipolar disorder. However, the relatively
      limited variance explained by the independent variables included in the study,
      suggests the need to examine other (perhaps non-clinical) factors that may affect
      QOL.

PMID- 15149300
TI  - Electroencephalogram-triggered functional magnetic resonance imaging in focal
      epilepsy.
AB  - The high spatial resolution and cost performance of functional magnetic resonance
      imaging (fMRI) is useful for estimating focus localization in epilepsy, but this
      is difficult in the case of ictal fMRI because this is susceptible to motion
      artifacts. Electroencephalogram (EEG)-triggered fMRI, which is interictal, can be
      performed without marked movement and is thought to be useful, but requires
      further investigation in order to establish a methodology. The authors studied
      EEG-triggered fMRI in partial epileptic patients. Six patients were examined
      using a Nihon Kohden digital EEG recorder and Signa Horizon High Speed LX 1.5 T
      MRI scanner. Six electrodes were attached in the vicinity of the focus detected
      by scalp EEG. The fMRI scans were recorded after the discharges (activation) and
      scans without spikes (baseline). Equal numbers of activation and baseline scans
      were collected and analyzed using SPM99. In three of the six patients, an
      activated area was observed near the focus, but no activated areas were found in
      the other three subjects who tended to have a low number of spikes and low spike
      amplitude. Although various approaches focusing on improvement of the
      activation/non-activation ratio are required, EEG-triggered fMRI is a promising
      technique for detecting focal epileptic brain activity.

PMID- 15149301
TI  - Clinical correlates of antipsychotic polytherapy in patients with schizophrenia
      in Singapore.
AB  - The purpose of the present study wa to determine the prevalence of antipsychotic
      polytherapy (use of more than one antipsychotic drug at one time) and its
      clinical correlates among 300 hospitalized psychotic Asian patients diagnosed
      with schizophrenia. It was hypothesized that such treatment would be associated
      with more severe illness than in comparable monotherapy patients, and with higher
      chlorpromazine-equivalent (CPZ) total daily doses. Clinical and demographic
      details were obtained from the medical records and direct clinical examinations.
      Polytherapy was encountered in 215 of the 300 patients (71.7%), with an average
      number of 1.8 antipsychotics (range 1-4) prescribed at a mean CPZ daily dose of
      612 +/- 528 mg (median: 464 mg, range: 25-2500 mg). The 215 patients prescribed
      more than one antipsychotic agents were younger, ill longer, more likely to be
      taking at least one high-potency agent, in receipt of higher average daily CPZ
      doses, and more likely to be prescribed anticholinergic agents but with similar
      admission illness severity rating (Brief Psychiatric Rating Scale) scores
      compared to the 85 patients given only one antipsychotic drug at one time. The
      high rate of antipsychotic polytherapy that appeared to be unrelated to current
      illness severity suggests that this practice may not consistently be based on
      rational therapeutic principles.

PMID- 15149302
TI  - Relation between cortical dopamine D(2) receptor occupancy and suppression of
      conditioned avoidance response in non-human primate.
AB  - Suppression of the conditioned avoidance response (CAR), a useful test for
      screening for antipsychotic effects, has been discussed in relation to the
      blockade of dopaminergic transmission. The purpose of the present paper was to
      investigate the relationship between cortical dopamine D(2) receptor occupancy
      and the suppression of CAR by haloperidol in non-human primate. The avoidance
      rate was measured for four different doses of haloperidol treatment in a rhesus
      monkey, and the cortical D(2) receptor occupancy was measured in a parallel
      session using positron emission tomography with [(11)C]FLB 457. The successful
      avoidance response rate was decreased for doses of 10 and 30 microg/kg of
      haloperidol, and this decrement was associated with 65-77% of D(2) receptor
      occupancy. It is suggested that the threshold level of cortical dopamine D(2)
      receptor occupancy for the suppression of CAR is demonstrated in the present
      study.

PMID- 15149303
TI  - Identification of a male schizophrenic patient carrying a de novo balanced
      translocation, t(4; 13)(p16.1; q21.31).
AB  - Herein is reported the case of a male patient with schizophrenia who displayed a
      de novo balanced translocation between the short arm of chromosome 4 and the long
      arm of chromosome 13, t(4; 13)(p16.1; q21.31). The 4p16.1 region is where the
      causative gene (WFS1) for Wolfram syndrome has been mapped. In Wolfram syndrome,
      approximately 60% of patients suffer from major mental illness. The other
      breakpoint, chromosome 13q21.31, is another region where previous linkage studies
      have repeatedly detected linkage to schizophrenia. The documentation of the
      present case could therefore provide a valuable resource for identifying disease
      susceptibility genes by localizing the breakpoints.

PMID- 15149304
TI  - Starvation-induced Wernicke's encephalopathy in schizophrenia.

PMID- 15149305
TI  - Case of bipolar disorder successfully stabilized with clonazepam, valproate and
      lithium after numerous relapses for 47 years.

PMID- 15149306
TI  - Principles of antiepileptic drug treatment of epilepsy.
AB  - For the successful treatment of epilepsy, accurate diagnosis of epilepsy and
      epileptic seizures, and proper selection of antiepileptic drugs (AED) according
      to the classification of epileptic syndromes are fundamentally important.
      Efficacy of AED treatment, however, depends not only on its pharmacological
      action but also on its efficient use, namely a rationally thinking tailor-made
      treatment considering the characteristics of each patients, i.e. individual
      differences in pharmacokinetics, factors influencing AED concentrations, AED
      interactions, and comprehensively their life style and psychosocial factors.

PMID- 15149307
TI  - Therapy-resistant epilepsy in children: with the view of the long-term outcome.
AB  - Of 362 children with therapy-resistant epilepsy, 119 patients had generalized
      tonic seizures, which were the most common seizure type in patients with
      generalized epilepsy. The long-term observation of the patients with tonic
      seizures revealed that their seizures were completely controlled in 27 patients
      for more than 5 years. The effective antiepileptic drugs were VPA (10 patients),
      PHT (5), CLB (4), ZNS (2), VPA + PHT (4), ZNS + CLB (1) and VPA + AZA (1). For
      obtaining improvement of tonic seizures, another strong factor is reducing the
      number of antiepileptic drugs, such as the average number of drugs, which was 4.7
      to 2.4 in these 27 patients.

PMID- 15149308
TI  - Etiologic factors and clinical features of symptomatic epilepsy: focus on
      pediatric cases.
AB  - We discuss the presumptive etiologic factors of symptomatic epilepsy from the
      clinical standpoint, based on our experience of 383 inpatients with epilepsy,
      with a focus on children. The main (top three) presumptive etiologic factors in
      partial epilepsy are intracranial infection, cerebral malformation and perinatal
      brain damage. In generalized epilepsy, the main presumptive etiologic factors are
      perinatal brain damage, intracranial infection, and cerebral malformation. As
      regards presumptive etiologic factors in partial epilepsy, cerebral malformation
      was most common in frontal lobe epilepsy, initial convulsive status in temporal
      lobe epilepsy and perinatal brain damage in occipital lobe epilepsy.
      Electroclinical characteristics of severe myoclonic epilepsy in infancy, the most
      intractable epilepsy syndrome in infancy, is the focus and recent advances of
      genetic research are introduced.

PMID- 15149309
TI  - Neuroimaging and presurgical evaluation of symptomatic epilepsies.
AB  - The goal of presurgical evaluation of intractable epilepsy is to identify
      epileptogenic regions in the brain. From our experience of 38 cases of resective
      epilepsy surgery from the last 3 years, ictal SPECT was considered the most
      sensitive at detecting focal changes relating to seizures compared to other
      neuroimaging modalities, such as MRI, FDG-PET, SPECT and MEG. At interictal
      state, on the other hand, FDG-PET was most sensitive, especially in cases with
      focal cortical dysplasia, which is often MRI-invisible. In dysplastic tumors, MRI
      showed the highest concordance rate to clinically verified epileptogenic regions.
      Activation studies using functional neuroimaging such as PET and fMRI is useful
      to evaluate brain functions at epileptogenic regions presurgically. The role of
      functional brain imaging in epilepsy surgery is considered to be: (i). case
      selection for resective surgery, (ii). case selection for invasive EEG
      monitoring, and (iii). navigation of electrode placement and cortical resection.

PMID- 15149310
TI  - Preoperative mapping for patients with supplementary motor area epilepsy:
      multimodality brain mapping.
AB  - Surgical management and strategies for the supplementary motor area (SMA)
      epilepsy are described. The following is our preoperative evaluations. The steps
      include functional magnetic resonance imaging (fMRI), interictal dipole tracing
      (DT), subdural electrodes mapping, measurements of movement-related cortical
      potential (MRCP), and the use of the intraoperative open MRI under conscious
      craniotomy. Six patients with SMA epilepsy underwent surgery after the mapping
      procedures and are now seizure-free. Combinations of preoperative (fMRI, subdural
      electrodes mapping) and intraoperative mapping allow exact localization and
      identification of the critical functional areas. Early postoperative deficits in
      motor and speech function were profound but patients recovered rapidly. It is
      concluded that the step of mapping procedures plays an important role in the
      management of SMA epilepsy surgery.

PMID- 15149312
TI  - Clinical and experimental studies of epilepsy associated with focal cortical
      dysplasia.
AB  - The results of clinical and experimental studies on epilepsy associated with
      focal cortical dysplasia (FCD) are presented. We have been interested in the
      findings of abnormal increases in the numbers of small vessels in specimens of
      FCD resected from epilepsy patients. In the clinical study of 13 patients with
      epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were
      examined using immunohistochemistry. The number of vessels in both lesions were
      greater than those in cortical specimens of autopsy cases without epilepsy.
      Because the vessels showed negative staining of VEGF, it was thought that the
      phenomenon of increase in the number of vessels was simply a hypervascularity,
      not a neovascularity. The local hypervascularity was expected to show local
      hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local
      hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by
      a functional change in those vessels. In the experimental study, we tried to make
      a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had
      been infused into the neocortex in the neonatal rats, FCD was induced in adult
      Wistar rats. Histopathological examination revealed cortical dyslamination and
      abnormal neurons. On EEG, local spike bursts were elicited from the lesions,
      however, clinical seizures were not detected. Although the data are preliminary
      and observation over a longer period is required to determine whether spontaneous
      seizures will occur in this model, it is expected that this new model will be
      useful for studying epilepsy associated with FCD.

PMID- 15149311
TI  - Long-term seizure outcome following resective surgery at National Epilepsy Center
      in Shizuoka, Japan.
AB  - We analyzed the seizure outcome of 357 patients who were followed for at least 2
      years after resective surgeries; 282 underwent temporal lobe resection and 75 had
      extratemporal lobe resection. This study confirmed that resective surgery
      provides sustained, positive benefits with a high seizure-free rate of nearly 80%
      for most medically refractory patients. In patients with no MRI-detectable lesion
      who underwent extratemporal lobe resection, however, Engel's class I-II (seizure
      free or rare seizures) was achieved in less than 50% of patients. High-resolution
      MRI should be performed at the early stage of disease in all patients with
      partial epilepsies. The findings would certainly urge clinicians to actively
      select surgical intervention.

PMID- 15149313
TI  - Differential effects of calcium antagonist subclasses on markers of nephropathy
      progression.
AB  - BACKGROUND: Numerous studies suggest that the dihydropyridine calcium antagonists
      (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential
      antiproteinuric effects. Proteinuria reduction is a correlate of the progression
      of renal disease. In an earlier systematic review, calcium antagonists were shown
      as effective antihypertensive drugs, but there was uncertainty about their renal
      benefits in patients with proteinuria and renal insufficiency. METHODS: A
      systematic review was conducted to assess the differential effects of DCAs and
      NDCAs on proteinuria in hypertensive adults with proteinuria, with or without
      diabetes, and to determine whether these differential effects translate into
      altered progression of nephropathy. Studies included in the review had to be
      randomized clinical trials with at least 6 months of treatment, include a DCA or
      NDCA treatment arm, have one or more renal end points, and have been initiated
      after 1986. Summary data were extracted from 28 studies entered into two
      identical but separate databases, which were compared and evaluated by
      independent reviewers. The effects of each drug class on blood pressure (N= 1338)
      and proteinuria (N= 510) were assessed. RESULTS: After adjusting for sample size,
      study length, and baseline value, there were no statistically significant
      differences in the ability of either class of calcium antagonist to decrease
      blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for
      NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in
      proteinuria were associated with the use of NDCAs compared with DCAs, despite no
      significant differences in blood pressure reduction or presence of diabetes.
      CONCLUSION: This analysis supports (1) similar efficacy between subclasses of
      calcium antagonists to lower blood pressure, and (2) greater reductions in
      proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes.
      Based on these findings, NDCAs, alone or in combination with an angiotensin
      converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), are
      suggested as preferred agents to lower blood pressure in hypertensive patients
      with nephropathy associated with proteinuria.

PMID- 15149314
TI  - The role of vascular endothelial growth factor (VEGF) in renal pathophysiology.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial-specific growth
      factor that promotes endothelial cell proliferation, differentiation and
      survival, mediates endothelium-dependent vasodilatation, induces microvascular
      hyperpermeability and participates in interstitial matrix remodeling. In the
      kidney, VEGF expression is most prominent in glomerular podocytes and in tubular
      epithelial cells, while VEGF receptors are mainly found on preglomerular,
      glomerular, and peritubular endothelial cells. The role of VEGF in normal renal
      physiology is essentially unknown. The absence of prominent effects of VEGF
      blockade in normal experimental animals suggests a limited function during
      homeostasis, although a role in the formation and maintenance of glomerular
      capillary endothelial fenestrations has been suggested. VEGF and its receptors
      are up-regulated in experimental animals and humans with type 1 and type 2
      diabetes. Inhibition of VEGF has beneficial effects on diabetes-induced
      functional and structural alterations, suggesting a deleterious role for VEGF in
      the pathophysiology of diabetic nephropathy. VEGF is required for glomerular and
      tubular hypertrophy and proliferation in response to nephron reduction, and loss
      of VEGF is associated with the development of glomerulosclerosis and
      tubulointerstitial fibrosis in the remnant kidney. No firm conclusions on the
      role of VEGF in minimal change or membranous glomerulonephritis can be drawn.
      VEGF may be an essential mediator of glomerular recovery in proliferative
      glomerulonephritis. Glomerular and tubulointerstitial repair in thrombotic
      microangiopathy and cyclosporin nephrotoxicity may also be VEGF-dependent. In
      conclusion, VEGF is required for growth and proliferation of glomerular and
      peritubular endothelial cells. While deleterious in some, it may contribute to
      recovery in other forms of renal diseases.

PMID- 15149315
TI  - EGF-related growth factors in the pathogenesis of murine ARPKD.
AB  - BACKGROUND: Epidermal growth factor (EGF), transforming growth factor-alpha (TGF
      alpha) and their receptor, EGFR, play key roles in polycystic kidney disease
      (PKD) pathogenesis. Renal expression of two related growth factors, amphiregulin
      and heparin-binding EGF, has not been examined previously in PKD. The aims of
      this study of murine autosomal-recessive polycystic kidney disease (ARPKD) were
      (1) to characterize amphiregulin and heparin-binding EGF expression in cystic
      versus normal kidneys and cells; and (2) to identify the functional effects of
      abnormal EGF-related growth factor expression. METHODS: Amphiregulin and heparin
      binding-EGF expression were examined by immunohistology and Western blot of
      kidneys and conditionally-immortalized collecting tubule cells obtained from
      cystic bpk mice (a murine model of ARPKD) and normal littermates. EGF, TGF-alpha,
      amphiregulin, and heparin-binding EGF in vitro effects on cystic and control
      collecting tubule cells were assessed by cell proliferation, cyst fluid
      mitogenicity, and EGFR activation. RESULTS: By immunohistology, amphiregulin and
      heparin-binding EGF localized to apical and basolateral surfaces of proximal
      tubule cysts > normal proximal tubules. In cystic collecting tubules, heparin
      binding EGF (but not amphiregulin) localized to both apical and basolateral
      surfaces; whereas in normal collecting tubules, amphiregulin and heparin-binding
      EGF localized to the basolateral surface only. Increased amphiregulin and heparin
      binding EGF expression by Western blot was seen in cystic vs. normal kidneys and
      increased heparin-binding EGF (but not amphiregulin) expression was present in
      cystic collecting tubule cell lines vs. controls. EGF, TGF-alpha, amphiregulin,
      and heparin-binding EGF were all mitogenic to cystic > control collecting tubule
      cells. Immunoprecipitation of EGF and TGF-alpha reduced cyst fluid mitogenicity
      by almost 80%, whereas heparin-binding EGF and amphiregulin immunoprecipitations
      had minimal effects. Differential receptor activation was also seen: Heparin
      binding EGF markedly activated EGFR (>EGF = TGF-alpha > amphiregulin), with a
      greater effect seen in cystic vs. control collecting tubule cells. CONCLUSION:
      Multiple EGF-related growth factors are abnormally expressed in murine ARPKD and
      may have differential roles in disease pathogenesis. In particular, newly
      identified abnormalities in heparin-binding EGF expression in cystic kidneys and
      cells may have important implications for disease pathogenesis.

PMID- 15149316
TI  - A large tandem duplication within the COL4A5 gene is responsible for the high
      prevalence of Alport syndrome in French Polynesia.
AB  - A large tandem duplication within the COL4A5 gene is responsible for the high
      prevalence of Alport syndrome in French Polynesia. Background. The prevalence of
      X-linked Alport syndrome, a progressive inherited nephropathy associated with
      mutations in the type IV collagen gene COL4A5, is remarkably high in French
      Polynesia. Methods. A vast clinical, genealogic, and molecular study was
      undertaken in Polynesia, based on public records, patients' interviews, linkage
      analysis, and mutation screening. Results and Conclusions. We show that the high
      frequency of Alport syndrome in this region is due to a founder mutation that
      occurred onto a common haplotype shared by affected and unaffected individuals,
      the presence of which precludes indirect molecular diagnosis. We have
      characterized the mutation as a tandem duplication of 35 COL4A5 exons, resulting
      in a approximately 65% increase in the length of the collagenous domain of the
      alpha 5(IV) chain, which is still able to assemble into type IV collagen network
      as shown by immunofluorescence analysis. That mutation is associated with severe
      and highly penetrant ocular symptoms and with uniformly thin glomerular basement
      membrane (GBM) in male adult patients. However, the rate of progression of the
      renal disease is very variable from one male patient to another, demonstrating
      the importance of strong modifier factors. Our results suggest that the 20% to
      50% of "missing"COL4A5 mutations in X-linked Alport syndrome may be
      rearrangements similar to that reported here, which was not detectable by
      sequencing of either individual COL4A5 exons or overlapping cDNA fragments.
      Finally, we provide the basis for a polymerase chain reaction (PCR) assay that
      accurately identifies female carriers and allows adequate genetic counseling in
      this population.

PMID- 15149317
TI  - Electroporation-mediated HGF gene transfer ameliorated cyclosporine
      nephrotoxicity.
AB  - BACKGROUND: The clinical utility of cyclosporine A (CsA) has been limited by its
      nephrotoxicity, which is characterized by tubular atrophy, interstitial fibrosis,
      and progressive renal impairment. Hepatocyte growth factor (HGF) has been
      reported to protect and salvage from renal injury as a renotropic and
      antifibrotic factor. Here, we investigated protective effects of HGF gene therapy
      on rat CsA-induced nephrotoxicity using electroporation-mediated gene transfer.
      METHOD: CsA was subcutaneously administered daily under low sodium diet, and HGF
      gene was transferred into skeletal muscle by electroporation on days 7 and 14. We
      also examined the antiapoptotic mechanism of HGF using human proximal tubular
      epithelial cells. RESULTS: HGF gene transfer rescued CsA-induced initial tubular
      injury and suppressed interstitial infiltration of ED-1-positive macrophages in
      CsA-induced nephrotoxicity. In addition, HGF significantly inhibited tubular cell
      apoptosis, and increased the number of proliferating tubular epithelial cells. In
      vitro studies suggest that HGF executes the antiapoptotic function by enhancing
      the phosphorylation of Akt and Bcl-2. Northern blot analysis demonstrated that
      HGF gene transfer suppressed cortical mRNA levels of transforming growth factor
      beta (TGF-beta). Consequently, HGF gene transfer significantly reduced a striped
      interstitial phenotypic alteration and fibrosis. CONCLUSION: We demonstrated that
      HGF gene transfer reduced CsA-induced tubular cell apoptosis and interstitial
      fibrosis. HGF gene transfer could be a potential strategy for preventing renal
      fibrosis.

PMID- 15149318
TI  - Relaxin-1-deficient mice develop an age-related progression of renal fibrosis.
AB  - BACKGROUND: Relaxin (RLX) is a peptide hormone that stimulates the breakdown of
      collagen in preparation for parturition and when administered to various models
      of induced fibrosis. However, its significance in the aging kidney is yet to be
      established. In this study, we compared structural and functional changes in the
      kidney of aging relaxin-1 (RLX-/-) deficient mice and normal (RLX+/+) mice.
      METHODS: The kidney cortex and medulla of male and female RLX+/+ and RLX-/- mice
      at various ages were analyzed for collagen content, concentration, and types.
      Histologic analysis, reverse transcription-polymerase chain reaction (RT-PCR) of
      relaxin and relaxin receptor mRNA expression, receptor autoradiography,
      glomerular isolation/analysis, and serum/urine analysis were also employed.
      Relaxin treatment of RLX-/- mice was used to confirm the antifibrotic effects of
      the peptide. RESULTS: We demonstrate an age-related progression of renal fibrosis
      in male, but not female, RLX-/- mice with significantly (P < 0.05) increased
      tissue dry weight, collagen (type I) content and concentration. The increased
      collagen expression in the kidney was associated with increased glomerular matrix
      and to a lesser extent, interstitial fibrosis in RLX-/- mice, which also had
      significantly increased serum creatinine (P < 0.05) and urinary protein (P <
      0.05). Treatment of RLX-/- mice with relaxin in established stages of renal
      fibrosis resulted in the reversal of collagen deposition. CONCLUSION: This study
      supports the concept that relaxin may provide a means to regulate excessive
      collagen deposition during kidney development and in diseased states
      characterized by renal fibrosis.

PMID- 15149319
TI  - Angiotensin administration stimulates renal 11 beta-hydroxysteroid dehydrogenase
      activity in healthy men.
AB  - BACKGROUND: We examined whether acute administration of angiotensin modulates the
      activity of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), the intracellular
      enzyme catalyzing the interconversion between the hormonally active cortisol and
      inactive cortisone. METHODS: Twenty-one male healthy subjects were examined after
      1 week of a low- and high-salt diet (50 and 200 mmol/day, respectively). Separate
      infusions of angiotensin I (Ang I) and II (Ang II) were administered, both at
      rates of 4 and 8 ng/kg/min. The ratios of tetrahydrocortisol +
      allotetrahydrocortisol/tetrahydrocortisone (THF + allo-THF/THE) and of free
      cortisol/free cortisone (UFF/UFE) in urine were measured as indices of overall 11
      beta HSD set point and activity of renal 11 beta HSD type 2, respectively.
      Glomerular filtration rate (GFR) was measured by constant infusion of (125)I
      iothalamate. RESULTS: Ang I and Ang II infusion dose-dependently increased mean
      arterial blood pressure (MAP) and plasma aldosterone, and decreased plasma renin
      activity (PRA) and GFR at both diets. Ang I and Ang II infusion resulted in a
      dose-dependent decrease in the excretion of UFF, UFE, and of the UFF/UFE ratio at
      both diets, without changing the urinary (THF + allo-THF)/THE ratio. Salt
      restriction did not affect these 11 beta HSD variables, but was accompanied by a
      decrease in UFF and UFE excretion. CONCLUSION: This study suggests that acute
      angiotensin administration stimulates the activity of 11 beta HSD type 2 in human
      kidney. Angiotensin might therefore exert a dual effect on the mineralocorticoid
      receptor (i.e., an indirect agonistic effect by increasing aldosterone
      availability and a direct or indirect antagonistic effect by stimulation of renal
      11 beta HSD type 2 activity).

PMID- 15149320
TI  - Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition
      of renal COX-2 expression.
AB  - BACKGROUND: It is known that inhibition of cyclooxygenase (COX) impairs the renal
      actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits
      renal COX-2 expression. Therefore, we examined the interferences of CsA with the
      renal actions of loop diuretics. METHOD: We investigated the renal effects of
      furosemide administration (12 mg/day subcutaneously) in male Sprague-Dawley rats
      receiving in addition vehicle, CsA (15 mg/kg x day), rofecoxib (10 mg/kg x day),
      or a combination of both. RESULTS: CsA, rofecoxib, and their combination lowered
      the furosemide-induced increase of prostaglandin E(2) (PGE(2)) and of 6-keto
      prostaglandin F(1 alpha) (6-keto PGF(1 alpha)) excretion by 55% and by 70%. They
      also lowered furosemide stimulated renal excretion of sodium and water by about
      65% and 60%. Basal as well as furosemide-induced stimulation of plasma renin
      activity (PRA) and of renal renin mRNA was further enhanced by CsA. In contrast,
      rofecoxib attenuated the furosemide-induced rise of PRA and of renin mRNA, both
      in the absence and in the presence of CsA. In addition, the increase in plasma 6
      keto PGF(1 alpha) levels by furosemide was further enhanced by CsA and was
      attenuated by rofecoxib. CONCLUSION: Taken together, our data suggest that CsA
      acts as an antinatriuretic, likely by the inhibition of COX-2-mediated renal
      prostanoid formation. Since the furosemide-induced stimulation of the renin
      system is not attenuated by CsA but by COX-2 inhibition, we speculate that
      extrarenal COX-2-derived prostanoids may be involved in the stimulation of the
      renin system by CsA and by loop diuretics.

PMID- 15149321
TI  - Differential effects of peroxisome proliferator activated receptor-gamma (PPAR
      gamma) ligands in proximal tubular cells: thiazolidinediones are partial PPAR
      gamma agonists.
AB  - Background. Peroxisome proliferator activated receptors (PPARs) are ligand
      activated transcription factors with multiple effects on target cell function.
      PPAR gamma activity is regulated by extracellular signal-regulated protein kinase
      (ERK), mitogen-activated protein (MAP) kinase, and PPAR gamma ligands have
      varying effects on activity of ERK. Different PPAR gamma ligands have been shown
      to have both protective and detrimental effects in the kidney. Since
      transcriptional activation by different PPAR agonists is ligand- and depot
      specific PPAR gamma, we have examined the effects of different agonists on PPAR
      activity in the proximal tubule. METHODS: Opossum kidney cells were used in all
      experiments, transiently transfected with a PPAR response element luciferase
      reporter and subject to stimulation with various PPAR ligands. The role of ERK
      and phosphorylation in PPAR gamma activation were studied, as were the effects of
      PPAR agonists on ERK activation and cell proliferation. RESULTS: Transcriptional
      activity of PPAR was not stimulated by PPAR alpha agonists, and only very
      modestly stimulated by a PPAR beta agonist. The PPAR gamma agonists 15-deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), ciglitazone, and troglitazone
      stimulated significant transcriptional activation and phosphorylation of PPAR
      gamma. These effects were more marked with 15d-PGJ(2). Thiazolidinediones
      attenuated 15d-PGJ(2) evoked PPAR gamma activation and phosphorylation. ERK
      activity positively regulated PPAR activation. Only 15d-PGJ(2) stimulated ERK
      activity and cell proliferation, and these effects were also inhibited by
      thiazolidinediones. CONCLUSION: PPAR gamma agonists exert differential effects in
      proximal tubule cells with thiazolidinediones behaving as partial agonists.

PMID- 15149322
TI  - Losartan modulation on NOS isoforms and COX-2 expression in early renal
      fibrogenesis in unilateral obstruction.
AB  - BACKGROUND: Angiotensin II plays a central role in the initiation of renal
      fibrogenesis at a very early stage leading to a rapid progression in unilateral
      ureteral obstruction (UUO). We examined the effect of an angiotensin II receptor
      inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on
      nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and
      the significance of this interaction on interstitial fibrosis in UUO. METHODS:
      Rats underwent UUO for 24 hours or control sham operation after been treated with
      losartan in the drinking water at 10 mg/kg/day for 15 days. AT(1) receptor
      binding and distribution was determined by in situ autoradiographic study. Renal
      fibrosis was evaluated through the relative volume of the tubulointerstitium (Vv)
      measured by an image analyzer, and transforming growth factor-beta (TGF-beta) at
      mRNA levels. NOS activity, expression of NOS isoforms by reverse transcription
      polymerase chain reaction (RT-PCR) assay and COX-2 protein expression, were
      determined. RESULTS: After administration of a nonhypotensive dose of losartan
      prevention of renal fibrogenesis was demonstrated in obstructed kidneys by means
      of Vv values and TGF-beta mRNA expression near controls. Decreased AT(1) receptor
      binding density was observed in cortex and inner stripe of the outer medulla of
      nontreated obstructed kidney compared to control, whereas no differences were
      observed in ipsilateral UUO related to obstructed kidney-treated group. The
      increased inducible NOS (iNOS) activity and expression of obstructed kidney
      medulla, increased neuronal NOS (nNOS), and endothelial NOS (eNOS) isoforms
      expression and COX-2 protein expression in obstructed kidney cortex showed down
      regulation of iNOS, nNOS, and COX-2 with persistent levels of eNOS after losartan
      administration. CONCLUSION: These results allowed us to infer an interstitial
      fibrogenesis prevention independent action of losartan, involving NOS isoforms
      and COX-2, in unilateral obstructive nephropathy.

PMID- 15149324
TI  - Degradation of albumin by the renal proximal tubule cells and the subsequent fate
      of its fragments.
AB  - BACKGROUND: In view of recent reports of large amounts of albumin fragments
      present in normal urine we investigated the mechanism of albumin handling by the
      proximal tubule. METHODS: We injected (125)I-albumin intravenously in rats and
      measured the excretion of intact and degraded (125)I-albumin in the urine by
      trichloroacetic acid (TCA) precipitation. The excretion rate of intact (125)I
      albumin was compared to that obtained by routine radioimmunoassay (RIA). Human
      proximal tubular HK-2 cells were used to characterize the albumin receptor and
      study the degradation of albumin to peptides, establish their size by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration
      chromatography, and determine the direction in which the degradation products are
      removed from the cell. RESULTS: Following injection of (125)I-albumin
      intravenously into rats we recovered large quantities of (125)I-albumin fragments
      in urine and determined that 98% was in a highly degraded form and only 2% was
      intact. Only the intact albumin could be detected by RIA. We observed similar
      results in the urine of ex vivo kidneys perfused with (125)I-albumin. We found
      that (125)I-albumin was taken up by HK-2 cells via a receptor, degraded in the
      lysosomes and the peptides exocytosed to both the apical and basolateral sides of
      the cells. CONCLUSION: We conclude that normally the kidney degrades large
      amounts of albumin and that the degradation fragments appear in the urine. These
      findings are in sharp contrast with the established view that degraded albumin is
      completely reabsorbed into the blood stream.

PMID- 15149323
TI  - Parenteral iron therapy exacerbates experimental sepsis.
AB  - BACKGROUND: Catalytic iron can potentiate systemic inflammation via its pro
      oxidant effects. This raises the possibility that parenteral iron administration
      might exacerbate a concomitant septic state. This study sought to experimentally
      test this hypothesis. METHODS: Male CD-1 mice were subjected to experimental
      sepsis via intraperitoneal injection of heat-killed Escherichia coli +/-
      concomitant intravenous iron sucrose (Venofer; 2 mg). Nonseptic mice +/- iron
      therapy served as controls. Plasma tumor necrosis factor-alpha (TNF-alpha) levels
      were assessed 2 hours postinjections (serving as an inflammatory marker).
      Oxidative stress was gauged in heart or kidney tissue (at either 4 or 24 hours)
      by heme oxygenase-1 (HO-1) mRNA or protein levels. Overall sepsis severity was
      assessed by morbidity/mortality rates (at 24 hours). RESULTS: Iron alone or
      sepsis alone each induced oxidant stress in heart and kidney (HO-1 mRNA/protein
      increases). When iron and E. coli were coadministered, additive or synergistic HO
      1 mRNA/protein increments resulted. Iron injection alone only slightly raised TNF
      alpha levels (from 0 to 2.3 pg/mL; P= 0.01). However, iron approximately doubled
      the TNF-alpha increments which arose from the septic state (1400 --> 2600 pg/mL).
      Neither sepsis alone, nor iron alone, induced any mortality and no mice became
      moribund (0/24 mice). However, when iron + sepsis were combined, approximately
      60% of mice either died (5/12) or developed a moribund (2/12) state (P= 0.005).
      CONCLUSION: Parenteral iron administration can induce systemic oxidative stress
      and modest TNF-alpha release. However, when iron is given during experimental
      sepsis, profound increases in both processes, and approximately 60% mortality,
      result. Given that renal failure patients have decreased antioxidant defenses and
      intermittently develop bacteremia, the potential for parenteral iron therapy to
      exacerbate clinical sepsis needs to be addressed.

PMID- 15149325
TI  - Proximal tubular cytochrome c efflux: determinant, and potential marker, of
      mitochondrial injury.
AB  - BACKGROUND: Cytochrome c (cyt c) is released from mitochondria after tissue
      injury, but little is known of its subsequent fate. This study was undertaken to
      ascertain: (1) does cyt c readily gain access to the extracellular space; (2) if
      so, what are some determinants of this process; and (3) might cyt c release be a
      potentially useful marker of in vivo tissue damage. METHODS: Isolated mouse
      proximal tubules (PT) were subjected to site 1 (rotenone; Rot), site 2 (antimycin
      A, AA), or site 3 (hypoxic) respiratory chain blockade (+/- 2 mmol/L glycine, to
      prevent plasma membrane disruption/cell death). Alternatively, oxidant injury was
      imposed (Fe(2+) or cholesterol oxidase). Extra- and intracellular cyt c levels
      were quantified by Western blot. Plasma or urine cyt c levels were also
      determined after rhabdomyolysis or ischemic acute renal failure (ARF) (in mice),
      or clinical ARF. RESULTS: AA, Rot, and hypoxia caused variable degrees of PT cyt
      c release (AA >> rot approximately hypoxia), but at most, <20% of total cell
      content was involved. In contrast, Fe(2+) evoked approximately 65% cyt c efflux,
      and cholesterol oxidation caused approximately 100% cyt c release. Glycine did
      not block cyt c efflux, dissociating this process from plasma membrane
      disruption/necrotic cell death. After rhabdomyolysis, plasma cyt c levels rose
      and correlated with the severity of ARF (r, 0.93 vs. BUNs). Cyt c was detected in
      urine after both experimental and clinical ARF. CONCLUSION: Cell cyt c release is
      dependent on the site and the type of mitochondrial injury sustained. Oxidative
      injury, in general, and cholesterol oxidation, in particular, seem particularly
      relevant in this regard. After mitochondrial release, cyt c traverses plasma
      membranes, eventuating in the extracellular space. The data suggest that plasma
      and/or urine cyt c appearance might function as a clinically useful in vivo
      marker of mitochondrial stress and the tissue injury sustained.

PMID- 15149327
TI  - Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study
      of 126 cases.
AB  - BACKGROUND: Necrotizing and crescentic glomerulonephritis related to
      antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as
      "pauci-immune"; however, it is not unusual for renal biopsies in such cases to
      exhibit some immune complex deposition within glomeruli on immunofluorescence
      and/or electron microscopic study. The composition and intraglomerular
      localization of such deposits in ANCA-glomerulonephritis has not been widely
      studied, and their potential pathologic and clinical significance is not clear,
      although a possible synergistic effect between immune complexes and ANCA in
      producing more severe glomerulonephritis is suggested by some human and animal
      studies. METHODS: Electron micrographs from 126 renal biopsies showing
      necrotizing/crescentic glomerulonephritis characterized by positive ANCA serology
      [C-ANCA, anti-proteinase 3 (anti-PR3), or anti-myeloperoxidase (MPO)] or
      necrotizing arteritis in the absence of known ANCA results were examined for the
      presence, quantity, and location of electron-dense deposits. The presence or
      absence of such deposits was correlated with histologic findings (fraction of
      glomeruli with crescents and segmental necrotizing lesions, mesangial and
      endocapillary hypercellularity), immunofluorescence findings, and clinical data,
      including serum creatinine and 24-hour urine protein levels at the time of
      biopsy. RESULTS: Sixty-eight (54%) of these biopsies showed glomerular immune
      complex deposits on electron microscopy; 87% of the latter also showed positive
      immunofluorescence findings for at least one immunoglobulin or complement
      component, although staining was relatively mild in most instances (< or =2+ on a
      0 to 4+ scale in all but eight cases). Nearly half of biopsies negative for
      deposits by electron microscopy also showed positive immunofluorescence findings,
      though even more so than in cases with deposits on electron microscopy the
      intensity of immunofluorescence staining in these biopsies was typically very
      weak (trace or trace to 1+ in most cases, none >2+). Hypercellularity within the
      glomerular tuft was seen in 50% of biopsies with deposits on electron microscopy
      but only 14% of those without deposits; in each group this was usually mild and
      mesangial. Notably, the presence of deposits on electron microscopy was
      associated with a higher median level of proteinuria (3.2 versus 1.3 g/24 hours,
      P < 0.0001) and a higher median percentage of glomeruli with crescents (62.5%
      versus 44.0%, P= 0.06). CONCLUSION: Immune complex deposits were found on
      electron microscopy in just over half of renal biopsies with crescentic
      glomerulonephritis associated with positive ANCA serology and/or necrotizing
      arteritis. Clinical correlations suggest that these immune complex deposits may
      somehow potentiate the effect of ANCA in producing glomerulonephritis.

PMID- 15149326
TI  - Suppression of chaperone-mediated autophagy in the renal cortex during acute
      diabetes mellitus.
AB  - BACKGROUND: In the renal hypertrophy that occurs in diabetes mellitus, decreased
      proteolysis may lead to protein accumulation, but it is unclear which proteins
      are affected. Because the lysosomal proteolytic pathway of chaperone-mediated
      autophagy is suppressed by growth factors in cultured cells, we investigated
      whether the abundance of substrates of this pathway increase in diabetic
      hypertrophy. METHODS: Rats with streptozotocin (STZ)-induced diabetes were pair
      fed with vehicle-injected control rats. Proteolysis was measured as lysine
      release in renal cortical suspensions and protein synthesis as phenylalanine
      incorporation. Target proteins of chaperone-mediated autophagy were measured in
      cortical lysates and nuclear extracts by immunoblot analysis. Proteins that
      regulate chaperone-mediated autophagy [the lysosomal-associated membrane protein
      2a (LAMP2a) or the heat shock cognate protein of 73 kD (hsc-73)] were measured in
      lysosomes isolated by density gradient centrifugation. RESULTS: Proteolysis
      decreased by 41% in diabetic rats; protein synthesis increased at 3 days, but
      returned to baseline by 7 days. The abundance of proteins containing that
      chaperone-mediated autophagy KFERQ signal motif increased 38% and individual
      KFERQ containing proteins [e.g., M2 pyruvate kinase, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and pax2] were more abundant. LAMP2a and hsc73 decreased by
      25% and 81%, respectively, in cortical lysosomes from diabetic vs. control rats.
      CONCLUSION: The decline in proteolysis in acute diabetes mellitus is associated
      with an increase in proteins degraded by chaperone-mediated autophagy and a
      decrease in proteins which regulate this pathway. This study provides the first
      evidence that reduced chaperone-mediated autophagy contributes to accumulation of
      specific proteins in diabetic-induced renal hypertrophy.

PMID- 15149328
TI  - Expression of angiotensinogen in proximal tubule as a function of glomerular
      filtration rate.
AB  - BACKGROUND: Proximal tubule (PT) angiotensinogen (AGT) is part of a tubular renin
      angiotensin system (RAS) that participates in the regulation of sodium
      reabsorption along the entire nephron. Physiologic maneuvers affecting AGT
      expression in PT also affect systemic RAS. Here, we tested the hypothesis that PT
      AGT is regulated by increased glomerular filtration rate (GFR). METHODS: Complete
      unilateral nephrectomy (UNX) in mice was used to induce a sustained increase in
      GFR in the remaining kidney. AGT expression was monitored by quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). AGT protein in PT was
      investigated by semiquantitative histology. We also measured AGT concentration in
      plasma and in 24-hour urine by a specific enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Seven weeks after nephrectomy, UNX animals exhibited a 2-fold
      increase in tubular AGT mRNA (P <.001) compared with sham-operated control
      animals. The proportion of PT sections exhibiting AGT immunostaining was
      significantly increased at day 3 (P <.05), and remained elevated at seven weeks
      (UNX = 0.63 +/- 0.09, sham = 0.38 +/- 0.02, P <.01), revealing recruitment of AGT
      producing cells along the PT. AGT excretion in final urine corrected for
      creatinine and kidney weight was also elevated by UNX at seven weeks (UNX = 209
      +/- 42 pmol/mg/g, sham = 147 +/- 29 pmol/mg/g, P <.05), with no difference in
      plasma AGT between UNX and control animals. CONCLUSION: These observations
      suggest that AGT expression in PT adapts in the long-term to changes in GFR. In
      the UNX model, urinary AGT excretion is also elevated as a consequence of
      increase in net tubular flow.

PMID- 15149329
TI  - Gentamicin treatment induces simultaneous mesangial proliferation and apoptosis
      in rats.
AB  - BACKGROUND: Gentamicin (G)-induced acute renal failure is characterized by an
      impairment of glomerular function without apparent changes in glomerular
      structure. However, G stimulates reactive oxygen species (ROS)-mediated mesangial
      cell proliferation in vitro. We studied whether G promotes mesangial cell
      apoptosis in vitro, and if apoptosis and proliferation in parallel may occur in
      glomerular cells in vivo after a renal damage induced by G treatment. METHODS:
      For in vivo studies, rats were treated with G (100 mg/kg body weight/day) for 6
      days, and functional and histologic studies were performed. For in vitro studies,
      mesangial cell proliferation and apoptosis were evaluated after 24, 48, and 72
      hours of 10(-5) mol/L G incubation. RESULTS: After G injections, the number of
      nuclei per glomerulus did not change, whereas proliferating and apoptotic cell
      numbers increased. G increases DNA synthesis and cell number in cultured
      mesangial cells, and increases markedly the apoptotic cell number. ROS scavengers
      superoxide dismutase and catalase reduce G-induced mesangial cell apoptosis,
      whereas the incubation with the ROS donor system xanthine plus xanthine oxidase
      increases apoptosis to levels similar to G. G-induced cellular proliferation and
      apoptosis either in vitro or in vivo is associated to an early increase in the
      pro-apoptotic protein Bax and a delayed increase in the survival protein Bcl-2.
      CONCLUSION: G simultaneously induces proliferation and apoptosis of mesangial
      cells in vitro and glomerular mesangial cells in vivo. ROS may mediate G-induced
      mesangial apoptosis in vitro. The equilibrium proliferation/apoptosis may
      maintain mesangial cell number within normal limits after a G-induced glomerular
      insult.

PMID- 15149330
TI  - Membrane proteinase 3 expression and ANCA-induced neutrophil activation.
AB  - BACKGROUND: Proteinase 3 is the major autoantigen in Wegener's granulomatosis
      (WG). Membrane PR3 expression is bimodal; low expressing cells (mPR3(low)) can be
      distinguished from cells with high expression (mPR3(high)) within a given
      individual. High mPR3 expression is a WG risk factor and is associated with
      relapse. However, no mechanisms for this important clinical observation have been
      provided. We tested the hypothesis that mPR3 expression, rather than the
      expression of other membrane molecules implicated in anti-neutrophil cytoplasmic
      autoantibodies (ANCA) activation, determines the robustness of the PR3-ANCA
      mediated response. METHODS: mPR3(low) and mPR3(high) neutrophils from a given
      individual were separated by magnetic cell sorting. Superoxide was measured by
      the ferricytochrome assay, and Akt phosphorylation by Western blotting. Double
      staining and flow cytometry were used to assay Fc gamma-receptor and beta 2
      integrin expression with respect to the mPR3 phenotype. Degranulation was
      measured via beta-glucuronidase activity, migration with fibronectin-coated
      transwells, and cell quantification by the myeloperoxidase (MPO) assay. RESULTS:
      PR3-ANCA-treated mPR3(high) versus mPR3(low) neutrophils showed more superoxide
      generation (33.7 +/- 15.2 nmol O(2) (-) to 14.6 +/- 8.4, P < 0.01), more
      degranulation (29%+/- 5 to 22%+/- 3, P < 0.05), and more PI3-K/Akt activation. In
      contrast, all responses in both mPR3 subsets were similar after other stimuli. We
      observed no differences in the beta 2-integrin, Fc gamma R IIa, and III
      expression with respect to the mPR3 subtype. Furthermore, we found no differences
      in the mobilization of PR3-containing granules and no differences in migration
      through fibronectin. CONCLUSION: The degree of neutrophil mPR3 expression has
      definitive functional consequences.

PMID- 15149331
TI  - In vitro study of the potential role of guanidines in leukocyte functions related
      to atherogenesis and infection.
AB  - BACKGROUND: The blunted immune response upon stimulation in chronic renal failure
      (CRF) is often coupled to a baseline inflammatory status which has been related
      to atherogenesis. Uremic biologic fluids and several specific uremic retention
      solutes alter cell-mediated immune responses, as well as the interaction of
      calcitriol with the immune system. METHODS: The present study evaluated the
      influence of different guanidino compounds on DNA synthesis, chemiluminescence
      production, and CD14 expression of undifferentiated and calcitriol-differentiated
      HL-60 cells. In a second setup, these guanidino compounds were evaluated for
      their specific effect on normal human leukocyte oxidative burst activity and
      tumor necrosis factor-alpha (TNF-alpha) expression. RESULTS: First, several
      guanidino compounds elicited proinflammatory effects on leukocytes.
      Methylguanidine and guanidine stimulated the proliferation of undifferentiated HL
      60 cells and the antiproliferative effect of calcitriol (P < 0.05) was
      neutralized in the presence of methylguanidine (P < 0.05) and guanidinosuccinic
      acid (P < 0.05). The phorbol-myristate-acetate (PMA)-stimulated chemiluminescence
      production of the calcitriol differentiated HL-60 cells was enhanced in the
      presence of guanidine (P < 0.05). Methylguanidine and guanidinoacetic acid
      enhanced the lipopolysaccharide (LPS)-stimulated intracellular production of TNF
      alpha by normal human monocytes (P < 0.05). Second, several guanidino compounds
      inhibited the function of leukocytes if they were activated. The PMA-stimulated
      chemiluminescence production of the calcitriol differentiated HL-60 cells was
      inhibited by the presence of methylguanidine (P < 0.05), guanidinoacetic acid (P
      < 0.05) and guanidinosuccinic acid (P < 0.05). After incubation of whole blood in
      the presence of methylguanidine, the Escherichia coli stimulated oxidative burst
      activity of the granulocyte population was significantly inhibited (P < 0.05). In
      addition, guanidinosuccinic acid had an inhibitory effect on the LPS-stimulated
      intracellular production of TNF-alpha by human monocytes (P < 0.01). CONCLUSION:
      Guanidino compounds exert proinflammatory as well as anti-inflammatory effects on
      monocyte/macrophage function. This could contribute to the altered prevalence of
      cardiovascular disease and propensity to infection in patients with CRF.

PMID- 15149332
TI  - Selective impairment of gene expression and assembly of nephrin in human diabetic
      nephropathy.
AB  - BACKGROUND: Recent disclosure of podocyte proteins has unraveled previously
      rather mysterious mechanisms that govern glomerular perm-selectivity in health
      and disease. Here we addressed the role of nephrin, CD2-associated protein
      (CD2AP), and podocin together with the integrity of the slit diaphragm in the
      pathogenesis of proteinuria of patients with diabetes and nephropathy. METHODS:
      Nephrin mRNA and protein expression were evaluated in parallel in adult diabetic
      patients by in situ hybridization and immunohistochemistry. For comparison,
      nondiabetic patients with minimal change nephrosis and normal control patients
      were evaluated. CD2AP and podocin expression by immunohistochemistry was also
      assessed. The filtration slit was analyzed by morphometry and transmission
      electron microscopy. RESULTS: Extracellular nephrin mRNA and protein were
      markedly reduced in diabetic patients. No changes were found in patients with
      minimal change versus controls. CD2AP and podocin were comparable in all
      subjects. Ultrastructural analysis showed in diabetic patients a remarkable
      reduction in the percentage of electron dense slit diaphragms, despite a
      frequency of the filtration slits comparable to control patients. CONCLUSION:
      Down-regulation of nephrin and loss of the electron dense structure of slit
      diaphragm indicate a novel mechanism accounting for proteinuria in diabetic
      nephropathy. To the extent that glomerular protein trafficking contributes to
      renal disease progression, our findings may have clinical relevance. Reduction of
      nephrin in the context of normal expression of CD2AP and podocin can be taken
      reasonably as a specific marker of renal disease in diabetes. Therapies targeted
      at correcting podocyte nephrin might be of value for diabetic medicine.

PMID- 15149333
TI  - Resistance to ischemic acute renal failure in the Brown Norway rat: a new model
      to study cytoprotection.
AB  - BACKGROUND: An in vivo model of intrinsic resistance to ischemia could be
      invaluable to define how specific pathways to injury or putative protectors from
      injury affect the severity of acute renal failure (ARF). The purpose of this
      study was to determine whether separate rat strains had differential sensitivity
      to renal ischemia, characterize the extent of protection, and begin to define
      differences in gene expression that might impact on the severity of ARF. METHODS:
      The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was
      compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd). Constitutive and
      inducible stress protein expression was compared between strains. RESULTS: At 24
      hours' reperfusion, SD rats had higher creatinine (3.4 mg/dL), elevated Na and
      water excretion, and proximal tubule necrosis. Both strains of BN rats were
      resistant to loss of renal function (Scr = 0.9 mg/dL at 24 hours' reflow) and had
      preserved renal morphology. BN rats had no redistribution of Na,K-ATPase into
      detergent-soluble cortical extracts found early (15 minutes) after ischemia in SD
      rats. Hsc73 expression did not differ between strains and was not induced by
      ischemia. Compared with SD, induction of Hsp25 and 72 by renal ischemia was
      blunted in both BN strains. Constitutive Hsp25 was higher in both BN-Mcw and BN
      Hsd compared with SD rat kidney. Constitutive Hsp72 was significantly higher only
      in BN-Mcw kidneys. Immunohistochemistry showed baseline Hsp72 and 25 expression
      was increased in proximal tubules of BN-Mcw versus SD. CONCLUSION: BN rat kidney
      is resistant to ischemic injury and provides a new model for studying
      cytoprotective mechanisms. Initial study of strain-specific gene expression
      suggests particular stress proteins are among the potential mechanisms
      contributing to protection against ARF.

PMID- 15149334
TI  - Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4.
AB  - BACKGROUND: Matrilysin, a secreted matrix metalloproteinase and target gene of
      Wnt signaling, functions in epithelial repair and host defense, but no role in
      renal injury has been described. METHODS: Matrilysin expression was assessed in
      human kidney specimens by immunohistochemistry, and in experimental renal injury
      in mice by immunohistochemistry, Northern blotting, and RNase protection assays
      (RPA). A relationship to Wnt4, which is also induced in renal injury, was
      determined by RPA and in situ hybridization. RESULTS: Matrilysin was not detected
      in the normal human renal tubular epithelium by immunohistochemistry. However,
      prominent staining was detected in sections from autosomal-dominant polycystic
      kidney disease in the cyst lining epithelium, atrophic tubules, and cyst
      micropolyps, and from hydronephrosis in dilated and atrophic tubules. Matrilysin
      expression was also induced by acute folic acid nephropathy and unilateral
      ureteral obstruction (UUO) in the mouse, and expression increased as acute injury
      progressed to tubulointerstitial fibrosis. Matrilysin staining was primarily
      localized to epithelium of distal tubule/collecting duct origin in both human and
      murine renal disease. Wnt signaling can induce matrilysin expression, and we
      found that the pattern of matrilysin expression during progression of renal
      fibrosis in the mouse after UUO or folic acid nephropathy, and in the jck model
      of murine polycystic kidney disease, closely paralleled that of Wnt4. CONCLUSION:
      These observations suggest that matrilysin may have a role in renal tubular
      injury and progression of tubulointerstitial fibrosis, and that Wnt4 may regulate
      matrilysin expression in the kidney.

PMID- 15149335
TI  - Isolation, culture, and characterization of endothelial cells from mouse
      glomeruli.
AB  - BACKGROUND: Cloned glomerular endothelial cells (GENC) have many potential uses
      and applications in immunologic and physiologic studies. Propagation of GENC has
      been difficult and available homogeneous GENC, particularly from mice, are
      limited. Herein we report isolation, cloning, propagation, and characterization
      of GENC from mice. METHODS: tsA58 immorto mice were used to isolate glomerular
      cells. Glomeruli were isolated by differential sieving, and decapsulated explants
      were cultured in permissive and optimal conditions for endothelial cells. The
      primary cells from glomerular outgrowths were expanded, taking advantage of the
      temperature-sensitive tsA58 gene, and then the cells were allowed to undergo
      spontaneous transformation. The cells were then sorted using anti-CD31 antibodies
      and their capacity to uptake acetylated-low-density lipoprotein (LDL). Individual
      subclones isolated by patch cloning were characterized using multiple markers.
      RESULTS: One of the homogeneous clones was morphologically endothelial-like,
      positive for CD31, CD106, CD62E, CD54, and acetylated-LDL uptake, formed tubes,
      and was negative for epithelial and mesangial cell markers. The functional
      properties of this GENC clone appeared to be intact, and signaling pathway was
      not altered. Two of the clones displayed the characteristics of either visceral
      epithelial or mesangial cells. CONCLUSION: The identified clones should have
      utility in multiple areas of investigation.

PMID- 15149336
TI  - Role of mast cells in the development of renal fibrosis: use of mast cell
      deficient rats.
AB  - BACKGROUND: Recent clinical studies have shown that the number of interstitial
      mast cells increases in various types of renal disease and correlates well with
      the magnitude of interstitial fibrosis. The present study was conducted to assess
      the role of mast cells in renal fibrosis by examining an experimental glomerular
      disease. METHODS: A rat model of chronic glomerular disease, puromycin
      aminonucleoside-nephrosis, was induced in mast cell-deficient (Ws/Ws) and normal
      (+/+) rats. RESULTS: The area of interstitial fibrosis was widely distributed at
      6 weeks in both groups of rats; however, unexpectedly, the area of interstitial
      fibrosis was greater in Ws/Ws rats than in +/+ littermates. Biochemical analysis
      of the hydroxyproline content confirmed the more severe fibrosis in the Ws/Ws
      rats. The number of mast cells increased in both Ws/Ws and +/+ rats, concomitant
      with the development of interstitial fibrosis, but was confirmed to be lower in
      Ws/Ws than in +/+ rats. There were no differences in the numbers of interstitial
      macrophages and T lymphocytes between the two groups. Reverse transcription
      polymerase chain reaction analysis of cytokine expression revealed that the level
      of mRNA for transforming growth factor-beta (TGF-beta), a potent profibrotic
      cytokine, was higher in Ws/Ws rats. In addition, heparin, one of the major
      components of mast cells, inhibited the expression of TGF-beta mRNA in rat
      fibroblasts in culture. CONCLUSION: These results suggest that mast cells do not
      play a major role in the pathogenesis of interstitial fibrosis in puromycin
      aminonucleoside nephrosis. Rather, they might be protective or ameliorative in
      this model through the inhibition of TGF-beta production by heparin, and possibly
      in other models and also in humans.

PMID- 15149337
TI  - Platelet inhibition limits TGF-beta overexpression and matrix expansion after
      induction of anti-thy1 glomerulonephritis.
AB  - BACKGROUND: Although a role of platelets is well established in atherosclerosis,
      only little is known about their contribution to pathologic renal matrix
      expansion. The present study analyzes the effect of the platelet inhibitor
      clopidogrel on the early injury and subsequent repair phase of experimental anti
      thy1 glomerulonephritis. METHODS: In male Sprague-Dawley rats, acute anti-thy1
      glomerulonephritis was induced by intravenous injection of OX-7 antibody. In
      protocol 1 (injury), clopidogrel was given starting 5 days before antibody
      injection. One day after disease induction, parameters of mesangial cell injury
      (glomerular cell number, inducible NO synthesis, and macrophage infiltration)
      were analyzed. In protocol 2 (repair), clopidogrel treatment was started one day
      after antibody injection. On day 6, parameters of glomerular repair [glomerular
      matrix score, expression of transforming growth factor (TGF)-beta 1, fibronectin,
      and plasminogen activator inhibitor (PAI)-1] and thrombosis (aneurysm formation
      and fibrinogen deposition) were determined. In both protocols, an additional
      group of rats was treated with the angiotensin-converting enzyme (ACE) inhibitor
      enalapril. RESULTS: In the injury protocol, platelet inhibition did not affect
      mesangial cell lysis, glomerular NO production, and macrophage infiltration,
      while ACE inhibition was protective. In the repair protocol, clopidogrel
      significantly limited aneurysm formation and fibrinogen deposition, as well as
      glomerular matrix expansion, TGF-beta 1, fibronectin, and PAI-1 expression. In
      comparison, enalapril was less effective in preventing glomerular thrombosis, but
      was significantly superior to clopidogrel in limiting matrix protein expression
      and accumulation. CONCLUSION: The present study shows that platelets play a
      significant role in the sequence from mesangial cell injury to renal matrix
      expansion in anti-thy1 glomerulonephritis. The results, directly comparing renin
      angiotensin-system and platelet inhibition, suggest that platelets contribute
      less than angiotensin II to TGF-beta overexpression and matrix accumulation in
      this model of acute glomerular wound repair.

PMID- 15149338
TI  - jun-N-terminal kinase regulates thrombin-induced PAI-1 gene expression in
      proximal tubular epithelial cells.
AB  - BACKGROUND: Interstitial activation of the coagulation cascade is a common
      finding in acute and chronic tubulointerstitial damage. We previously
      demonstrated that thrombin may induce proximal tubular epithelial cells (PTEC)
      proliferation and regulate, through plasminogen activator inhibitor (PAI)-1 and
      urokinase-type plasminogen activator (u-PA), their profibrotic activity. The
      signaling pathways leading to these effects are still unknown. The PAI-1 promoter
      contains several activator protein-1 (AP-1) consensus sequences. AP-1 activation
      is induced by different agonists through jun-N-terminal kinase (JNK). Thus, we
      investigated the role of the JNK-AP-1 axis on thrombin-induced PAI-1 and u-PA
      expression in immortalized PTEC and its modulation by PKC and src, two key
      signaling enzymes. METHODS: JNK and src activation was investigated by Western
      blotting, PAR-1 cellular surface expression by flow cytometry, PAI-1 and u-PA
      gene expression by Northern blotting, AP-1 activation by transient transfection,
      and DNA synthesis by (3)H-thymidine uptake. RESULTS: Thrombin and PMA induced a
      time-dependent increase of JNK phosphorylation in immortalized PTEC that was
      inhibited by PKC down-regulation. Both thrombin and PMA caused AP-1 activation,
      significantly reduced by src inhibition. Phorbol 12-myristate 13-acetate (PMA),
      indeed, induced an increase in src phosphorylation. Both PMA- and thrombin
      stimulated PAI-1 gene expression was abolished by JNK, protein kinase C (PKC),
      and src inhibition, and this effect was regulated at the trascriptional level.
      PKC, but not src or JNK inhibition, abolished thrombin-elicited u-PA expression.
      Finally, JNK inhibition did not influence thrombin-induced proliferation.
      CONCLUSION: Our data suggest that thrombin activates the JNK-AP-1 axis in a PKC-
      and src-dependent manner in PTEC. This axis, necessary for thrombin-stimulated
      PAI-1 expression, but not for its fibrinolytic and regenerative effect, may
      represent a therapeutic target in acute and chronic tubulointerstitial damage.

PMID- 15149339
TI  - Renal artery calcified plaque associations with subclinical renal and
      cardiovascular disease.
AB  - BACKGROUND: The prognostic significance of renal artery calcified plaque (RAC)
      and its relationship with renal function, albuminuria, and systemic
      atherosclerosis are unknown. METHODS: Calcified atherosclerotic plaque was
      measured in the renal arteries of 96 unrelated Caucasian subjects with type 2
      diabetes mellitus (DM) using four-channel multidetector-row computed tomography
      (MDCT4). Renal artery calcium was measured as the sum of ostial and main renal
      artery calcium scores. Participants also underwent MDCT scanning to measure
      coronary artery calcium (CAC), carotid artery calcium, common iliac artery
      calcium, infra-renal aorta calcium, and B-mode ultrasound to measure carotid
      artery intima-medial thickness (IMT). Spearman's rank correlation coefficients
      were used to assess associations between RAC and measures of subclinical renal
      and cardiovascular disease. Partial correlation coefficients were computed to
      adjust for the potential confounding effects of age, gender, body mass index
      (BMI), DM duration, smoking, and serum cholesterol and triglyceride levels.
      RESULTS: Characteristics of the study group were 54% (52/96) female with a mean
      +/- SD (median) age 62.8 +/- 8.4 (62.5) years, DM duration 10.6 +/- 6.3 (8.0)
      years, hemoglobin A1C 7.5 +/- 1.5 (7.2)%, BMI 32.1 +/- 6.3 (31.1) kg/m(2), serum
      creatinine concentration 1.11 +/- 0.18 (1.10) mg/dL, urine albumin:creatinine
      ratio (ACR) 105.3 +/- 423.1 (17.6) mg/g, modified MDRD equation glomerular
      filtration rate (GFR) 64.3 +/- 12.6 (63.6) mL/min, RAC 372 +/- 799 (101), CAC
      1819 +/- 2594 (622), carotid artery calcium 264 +/- 451 (72), and B-mode
      ultrasound carotid IMT 0.70 +/- 0.12 (0.69) mm. Sixty-five percent of subjects
      (62/96) had detectable RAC. Renal artery calcium was significantly associated
      with CAC (r= 0.50, P < 0.0001), carotid artery calcium (r= 0.58, P < 0.0001),
      common iliac artery calcium (r= 0.45, P < 0.0001), infra-renal aorta calcium (r=
      0.70, P < 0.0001), IMT (r= 0.40, P= 0.0004), diastolic blood pressure (r=-0.33,
      P= 0.0009), BMI (r=-0.19, P= 0.0573), and age (r= 0.54, P < 0.0001). There was no
      association between RAC and GFR (r=-0.15, P= 0.1637) or between RAC and urine ACR
      (r= 0.07, P= 0.5083). CONCLUSION: Renal artery calcium is strongly associated
      with older age, diastolic blood pressure, BMI, carotid artery IMT, and coronary,
      carotid, common iliac artery, and infra-renal aorta calcium in Caucasians with
      type 2 diabetes mellitus. Renal artery calcium, similar to CAC and IMT, appears
      to be a useful noninvasive marker of subclinical atherosclerosis. However, RAC is
      not significantly associated with either GFR or albuminuria.

PMID- 15149340
TI  - Nitric oxide synthase expression in AT2 receptor-deficient mice after DOCA-salt.
AB  - BACKGROUND: Angiotensin II type 2 receptor-deficient mice (AT(2)-/y) provide an
      opportunity to study the relationship between the angiotensin II type 1 receptor
      (AT(1)) and nitric oxide synthase (NOS) isoforms without concomitant AT(2)
      receptor-related effects. To test this relationship, the expression of renal NOS
      isoforms (neural, inducible, and endothelial) in AT(2)-/y and AT(2)+/y mice was
      examined. The mice were challenged with deoxycorticosterone acetate (DOCA)-salt
      to stimulate NO generation. METHODS: Gene expression analyses by real-time
      polymerase chain reaction (PCR) (TaqMan) were performed in kidneys to
      characterize neuronal nitric oxide synthase (nNOS), epithelial nitric oxide
      synthase (eNOS), inducible nitric oxide synthase (iNOS), and the AT(1) receptor.
      Pressure-natriuresis experiments were done to determine the physiologic
      background. RESULTS: AT(2)-/y mice showed nNOS and iNOS up-regulation. DOCA-salt
      increased iNOS expression more in AT(2)-/y mice than in AT(2)+/y mice.
      Immunohistochemistry localized the iNOS expression with DOCA-salt mainly in the
      glomeruli. eNOS was not different between the groups, and was not affected by
      DOCA-salt. DOCA-salt increased mean arterial pressure more in AT(2)-/y mice than
      in AT(2)+/y mice. Concomitantly, the pressure-natriuresis relationship was
      shifted to the right in AT(2)-/y and AT(2)+/y mice after DOCA-salt. DOCA-salt
      decreased renal blood flow (RBF) and glomerular filtration rate (GFR) in both
      groups. iNOS blockade did not lower blood pressure. CONCLUSION: We conclude that
      AT(2) receptor deletion and concomitant up-regulation of the AT(1) receptor is
      associated with up-regulation of nNOS and iNOS. Under DOCA-salt, renal iNOS
      expression was further increased. Because iNOS inhibition did not change blood
      pressure, iNOS may not be involved in the hemodynamics, but may contribute to
      organ damage.

PMID- 15149342
TI  - Relation of urinary albumin excretion to coronary heart disease and low renal
      function: role of blood pressure.
AB  - BACKGROUND: Previous studies report that urinary albumin excretion is associated
      with coronary heart disease (CHD). The present epidemiologic study investigated
      if (1) blood pressure status affects the association of urinary albumin excretion
      with CHD; and (2) urinary albumin excretion is associated with low renal function
      also. METHODS: The cross-sectional association was analyzed of overnight urinary
      albumin excretion with prevalence of CHD (myocardial infarction and/or ischemia
      as defined by standard electrocardiogram) and low renal function (overnight
      creatinine clearance <60 mL/min) in a population sample of 1632 men and women
      with ages 45 to 64 years. Hypertension, hypercholesterolemia, smoking habit, and
      diabetes mellitus were included in analyses. RESULTS: CHD prevalence was in the
      whole sample 8.2% (N= 134), in the hypertensive subgroup 11.9% (N= 79), and in
      the nonhypertensive subgroup 5.7% (N= 55). For the association between urinary
      albumin excretion (logarithm-transformed due to skewed distribution) and CHD, the
      multivariate logistic coefficient with 95% CI was significant in the whole sample
      (+0.79, 95% CI =+0.32/+1.26, P < 0.001) and in the hypertensive subgroup (+0.97,
      95% CI =+0.70/+1.24, P < 0.001), not in the nonhypertensive subgroup (-0.06, 95%
      CI =-0.80/+0.68, P= 0.997). Prevalence of low creatinine clearance was in the
      whole sample 4.0% (N= 66), in the hypertensive subgroup 4.8% (N= 32), and in the
      nonhypertensive subgroup 3.5% (N= 34). The logistic coefficient between urinary
      albumin excretion and low creatinine clearance was borderline significant in the
      whole sample (+0.56, 95% CI =-0.02/+1.14, P= 0.090), significant in the
      hypertensive subgroup (+0.73, 95% CI =+0.04/+1.42, P= 0.044), not significant in
      the nonhypertensive subgroup (-0.07, 95% CI =-1.25/+1.10, P= 0.913). CONCLUSION:
      Results support the use of urinary albumin excretion as marker of CHD and
      slightly reduced renal function in hypertensives.

PMID- 15149341
TI  - Oxidative stress and renal injury with intravenous iron in patients with chronic
      kidney disease.
AB  - BACKGROUND: Intravenous iron is widely prescribed in patients with chronic kidney
      disease (CKD) and can cause oxidative stress. The relationship of oxidative
      stress and renal injury in patients with CKD is unknown. Whether renal injury can
      occur at a time point when transferrin is incompletely saturated is also unclear.
      METHODS: We conducted a randomized, open-label, parallel group trial to compare
      the oxidative stress induced by intravenous administration of 100 mg iron sucrose
      over 5 minutes and its protection with N-acetylcysteine (NAC) in 20 subjects with
      stage 3 or 4 CKD. Transferrin saturation was measured with urea polyacrylamide
      gel electrophoresis, oxidative stress by malondialdehyde (MDA) measurement by
      high-performance liquid chromatography, and renal injury by enzymuria and
      proteinuria. Reduced and oxidized glutathione and free radical scavengers as well
      as urinary monocyte chemoattractant protein-1 were also measured. RESULTS:
      Parenteral iron increased plasma concentration and urinary excretion rate of MDA,
      a biomarker of lipid peroxidation, within 15 to 30 minutes of iron sucrose
      administration. This was accompanied by enzymuria and increase in proteinuria. In
      contrast, saturation of transferrin was not maximally seen until 3 hours after
      the end of infusion. Oxidative stress, enzymuria and proteinuria were transient
      and were completely resolved in 24 hours. NAC reduced acute generation of
      systemic oxidative stress but failed to abrogate proteinuria or enzymuria.
      CONCLUSION: Intravenous iron produces oxidative stress that is associated with
      transient proteinuria and tubular damage. The rapid production of oxidative
      stress even when transferrin is not completely saturation suggests free iron
      independent mechanism(s) to be operative in producing oxidative stress and
      transient renal injury. Long-term implications of these findings need further
      study.

PMID- 15149343
TI  - Age-specific familial risks for renal cell carcinoma with evidence on recessive
      heritable effects.
AB  - BACKGROUND: Systematic comparisons of mode of inheritance for renal cell
      carcinoma (RCC) have not been carried out. The occurrence of cancer in parents
      and offspring may be due to dominant causes, whereas cancer affecting only
      siblings may indicate a recessive causation. Environmental effects need to be
      excluded. METHODS: The Swedish Family-Cancer Database includes all Swedes born
      after 1931 with their biologic parents, totaling 10.2 million persons. Cancer
      data were retrieved from the Swedish Cancer Registry from years 1961 to 2000,
      included 2415 cases of RCC in offspring and 18531 in parents. Standardized
      incidence ratios (SIRs) and 95% CI limits were calculated for offspring whose
      parents or sibling were diagnosed with RCC. RESULTS: The SIRs for siblings for
      RCC depended on their age difference. SIR was 7.63 (95% CI 3.63-14.08) when the
      age difference was less than 3 years and compared to 3.43 (95% CI 1.77-6.02) for
      large age difference. SIRs for familial risk of RCC were 1.73 (95% CI 1.31-2.26)
      when a parent and 4.58 (95% CI 2.87-6.94) when a sibling had RCC. Age-specific
      analysis of familial RCC among siblings revealed maxima at ages 40 to 49 and 60
      to 68 years. CONCLUSION: The findings in the present study offer evidence on
      recessive effects in early onset RCC.

PMID- 15149344
TI  - Reduced renal function in patients with simple renal cysts.
AB  - BACKGROUND: Sporadic renal cysts not associated with genetic polycystic disorders
      are common and generally thought to be of no clinical significance. Since
      multiple cysts frequently develop in end-stage renal disease (ESRD), we tested
      the hypothesis that cysts that are solitary or few in number are an early
      manifestation of reduced renal function. METHODS: We evaluated 561 hospitalized
      patients who underwent contrast-enhanced, abdominal computed tomography (CT) and
      correlated clinical characteristics and parameters of renal function with the
      presence or absence of renal cysts. RESULTS: Age ranged from 16 to 100 years,
      mean serum creatinine concentration was 0.88 mg/dL (range 0.4 to 2.1 mg/dL), and
      mean estimated creatinine clearance was 94 mL/min/1.73 m(2) (range 22 to 218
      mL/min/1.73 m(2)). The presence of cysts was significantly correlated with older
      age (P < 0.001), higher serum creatinine concentration (P < 0.002), and lower
      estimated creatinine clearance (P < 0.001). In a multivariate analysis, including
      age and gender, estimated creatinine clearance still correlated with the presence
      of cysts (P= 0.009). When patients were grouped by age, estimated creatinine
      clearance correlated with cysts in patients <40 years and 40 to 59 years, but not
      in patients 60 to 79 years or > or =80 years. There was no association of cysts
      with hypertension or proteinuria. In patients with cysts, serum creatinine
      increased progressively but not significantly with cyst number, and did not
      correlate with size or distribution of cysts. Renal parenchymal volume was
      slightly but not significantly reduced in patients with cysts. CONCLUSION: The
      presence of kidney cysts, even single cysts, is associated with reduced renal
      function in hospitalized patients younger than 60 years. This relationship may be
      obscured by the reduced renal function and the high incidence of cysts in older
      patients. These results suggest that acquired cystic kidney disease may begin
      early in the course of renal disease and that underlying renal disease should be
      considered in individuals with renal cysts prior to age 60 years.

PMID- 15149345
TI  - Proteinuria, a target for renoprotection in patients with type 2 diabetic
      nephropathy: lessons from RENAAL.
AB  - BACKGROUND: Proteinuria or albuminuria is an established risk marker for
      progressive renal function loss. Albuminuria can be effectively lowered with
      antihypertensive drugs that interrupt the renin-angiotensin system (RAS). We
      investigated whether albuminuria could not only serve as a marker of renal
      disease, but also function as a monitor of the renoprotective efficacy of RAS
      intervention by the angiotensin II (Ang II) antagonist, losartan, in patients
      with diabetic nephropathy. METHODS: The data from the RENAAL (Reduction in End
      Points in Noninsulin-Dependent Diabetes Mellitus with the Angiotensin II
      Antagonist Losartan) study, a double-blind, randomized trial, were used to
      examine the effects of losartan on the renal outcome [i.e., the primary composite
      end point of doubling of serum creatinine, end-stage renal disease (ESRD) or
      death] in 1513 type 2 diabetic patients with nephropathy. We examined the effect
      of the degree of albuminuria at baseline, initial antiproteinuric response to
      therapy, and the degree of remaining (residual) albuminuria on renal outcome
      (either the primary composite end point of RENAAL or ESRD). We also evaluated the
      contribution to renal protection of the antiproteinuric effect of losartan
      independently of changes in blood pressure. RESULTS: Baseline albuminuria is
      almost linearly related to renal outcome, and is the strongest predictor among
      all measured well-known baseline risk parameters. After adjusting for baseline
      risk markers of age, gender, race, weight, smoking, sitting diastolic blood
      pressure, sitting systolic blood pressure, total cholesterol, serum creatinine,
      albuminuria, hemoglobin, and hemoglobin A(1c) (HbA(1c)) patients with high
      baseline albuminuria (> or =3.0 g/g creatinine) showed a 5.2-fold (95% CI 4.3
      6.3) increased risk for reaching a renal end point, and a 8.1-fold (95% CI 6.1
      10.8) increased risk for progressing to ESRD, compared to the low albuminuria
      group (<1.5 g/g). The changes in albuminuria in the first 6 months of therapy are
      roughly linearly related to the degree of long-term renal protection: every 50%
      reduction in albuminuria in the first 6 months was associated with a reduction in
      risk of 36% for renal end point and 45% for ESRD during later follow-up.
      Albuminuria at month 6, designated residual albuminuria, showed a linear
      relationship with renal outcome, almost identical to the relationship between
      baseline albuminuria and renal risk. Losartan reduced albuminuria by 28% (95% CI 
      25% to -36%), while placebo increased albuminuria by 4% (95% CI +8% to -1%) in
      the first 6 months of therapy. The specific (beyond blood pressure lowering)
      renoprotective effect of the Ang II antagonist, losartan, in this study is for
      the major part explained by its antialbuminuric effect (approximately 100% for
      the renal end point, and 50% for ESRD end point). CONCLUSION: Albuminuria is the
      predominant renal risk marker in patients with type 2 diabetic nephropathy on
      conventional treatment; the higher the albuminuria, the greater the renal risk.
      Reduction in albuminuria is associated with a proportional effect on renal
      protection, the greater the reduction the greater the renal protection. The
      residual albuminuria on therapy (month 6) is as strong a marker of renal outcome
      as is baseline albuminuria. The antiproteinuric effect of losartan explains a
      major component of its specific renoprotective effect. In conclusion, albuminuria
      should be considered a risk marker for progressive loss of renal function in type
      2 diabetes with nephropathy, as well as a target for therapy. Reduction of
      residual albuminuria to the lowest achievable level should be viewed as a goal
      for future renoprotective treatments.

PMID- 15149346
TI  - The effect of dialysis dose and membrane flux on nutritional parameters in
      hemodialysis patients: results of the HEMO Study.
AB  - BACKGROUND: The effect of standard or high dialysis dose and low or high dialysis
      flux on nutritional status was ascertained in 1846 maintenance hemodialysis
      patients enrolled in the HEMO Study. METHODS: Serum albumin levels, equilibrated
      protein catabolic rate, and postdialysis weight were obtained monthly, while
      adjusted protein and energy intake, self-reported appetite assessment, upper arm
      circumference, and calf circumference were obtained yearly. To account for
      patient attrition due to death or transfer, three statistical models were used to
      test the effects of the study interventions on longitudinal changes in
      nutritional parameters. RESULTS: During the first 3 years of follow-up, neither
      mean serum albumin levels, which declined by 0.21 g/dL, nor mean postdialysis
      weight, which declined by 2.7 kg, were significantly affected by either study
      intervention. Mean levels of all anthropometric measures declined during follow
      up. For years 1, 2, and 3, the mean +/- SE declines in upper arm and calf
      circumferences were 0.35 +/- 0.16 cm (P= 0.031) and 0.31 +/- 0.13 (P= 0.015) cm
      less, respectively, in the high flux compared to the low flux group. Appetite
      scores and mean equilibrated protein catabolic rate also declined in all
      randomized groups; however, the average decline in equilibrated protein catabolic
      rate during years 1, 2, and 3 was 0.019 +/- 0.007 g/kg/day less in the high dose
      than the standard dose group (P= 0.007). There was no significant change in
      either mean energy or protein intake from diet records over time, and neither
      parameter was affected by the study interventions. CONCLUSION: Although the dose
      and flux interventions may subtly influence certain nutritional parameters,
      neither intervention prevented deterioration in nutritional status over time.

PMID- 15149347
TI  - Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from
      three continents: the DOPPS.
AB  - BACKGROUND: Hepatitis C virus (HCV) remains a problem within hemodialysis units.
      This study measures HCV prevalence and seroconversion rates across seven
      countries and investigates associations with facility-level practice patterns.
      METHODS: The study sample was from the Dialysis Outcomes and Practice Patterns
      Study (DOPPS), a prospective, observational study of adult hemodialysis patients
      randomly selected from 308 representative dialysis facilities in France, Germany,
      Italy, Japan, Spain, the United Kingdom, and the United States. Logistic
      regression was used to model odds of HCV prevalence, and Cox regression was used
      to model time from study entry to HCV seroconversion. RESULTS: Mean HCV facility
      prevalence was 13.5% and varied among countries from 2.6% to 22.9%. Increased HCV
      prevalence was associated with longer time on dialysis, male gender, black race,
      diabetes, hepatitis B (HBV) infection, prior renal transplant, and alcohol or
      substance abuse in the previous 12 months. Approximately half of the facilities
      (55.6%) had no seroconversions during the study period. HCV seroconversion was
      associated with longer time on dialysis, human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS), HBV infection, and recurrent cellulitis or
      gangrene. An increase in highly trained staff was associated with lower HCV
      prevalence (OR = 0.93 per 10% increase, P= 0.003) and risk of seroconversion (RR
      = 0.92, P= 0.07). Seroconversion was associated with an increase in facility HCV
      prevalence (RR = 1.36, P < 0.0001), but not with isolation of HCV-infected
      patients (RR = 1.01, P= 0.99). CONCLUSION: There are differences in HCV
      prevalence and rate of seroconversion at the country and the hemodialysis
      facility level. The observed variation suggests opportunities for improved HCV
      outcomes.

PMID- 15149348
TI  - ACE inhibitor and angiotensin type I receptor antagonist in combination reduce
      renal damage in obese Zucker rats.
AB  - BACKGROUND: In this study, we evaluated whether a combination of an angiotensin
      converting enzyme (ACE) inhibitor, benazepril (B), with an angiotensin type I
      receptor antagonist (AT1RA), irbesartan (I), is as effective or more than drugs
      as monotherapy in controlling renal damage in obese Zucker rats (OZR), a model of
      metabolic syndrome. METHODS: During six months, G1 (OZR receiving no treatment);
      G2 (OZR with B 10 mg/kg/day); G3 (OZR with I 50mg/kg/day); and G4 (OZR with B
      5mg/kg/day + I 25 mg/kg/day). Kidneys were processed for light microscopy (LM)
      and immunohistochemistry, including antibodies against interstitial alpha-smooth
      muscle-actin (alpha-SMA), plasminogen activator inhibitor-1 (PAI-1), transforming
      growth factor-beta(1)(TGF-beta 1), and collagen (COL) I, III, and IV. RESULTS:
      All treated groups presented similar reduction in blood pressure compared with
      untreated OZR. However, animals from G4 (B + I) showed better control on
      proteinuria together with a higher creatinine clearance. Additionally, G4 showed
      a significant (P < 0.05) lower kidney weight; smaller glomerular area; lower
      glomerulosclerosis score; lower percentage of tubular atrophy, interstitial
      fibrosis, and interstitial alpha-SMA; lower tubular PAI-1 score; lower percentage
      of COL I, III, and IV in renal interstitium; and lower wall/lumen ratio in renal
      vessels, when compared with the other groups. OZR treated with B and/or I showed
      a better outcome (P < 0.01) in the carbohydrate and lipid metabolism in
      comparison with untreated OZR. CONCLUSION: These results suggest that combined
      therapy using B and I is more effective than therapy with either drug at
      monotherapy for controlling renal damage in this animal model. In addition, data
      presented here reaffirm the benefit of interacting against renin-angiotensin
      system (RAS) in the metabolic syndrome.

PMID- 15149349
TI  - Post-transplant nephrotic syndrome: A comprehensive clinicopathologic study.
AB  - BACKGROUND: Post-transplant (Tx) nephrotic syndrome (NS) is not well defined.
      METHODS: Seventy-four renal transplant recipients with NS were studied. RESULTS:
      Biopsies showed chronic allograft nephropathy (CAN) in 31 patients; recurrent
      glomerular disease (GN) in 15, de novo GN in 18, and undetermined GN in 9. NS
      developed 0.25 to 384 months post-Tx and was treated with angiotensin-converting
      enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in 18 patients;
      calcium channel blockers in 25; or both drugs in 31. NS remitted in 24% of cases
      2 to 28 months after onset, and this persisted in all except 3 patients. The
      remission rate was lowest (9%) for CAN and highest (47%) for de novo GN. Compared
      with persistent NS, those with remission showed higher prevalence of de novo GN
      (53% vs. 17%), lower prevalence of CAN (18% vs. 50%), earlier onset of NS (39 vs.
      59 months), lower serum SCr at onset (2.3 vs. 2.9 mg/dL), and higher incidence of
      treatment with ACE or ARB. The 5-year graft loss rates for CAN, recurrent and de
      novo GN were 57%, 36%, and 23%, respectively. Compared with the functioning
      grafts, the failed grafts showed higher prevalence of CAN (60% vs. 16%), lower
      prevalence of de novo GN (12% vs. 46%), earlier onset of NS (47 vs 65 months post
      Tx), higher serum SCr at onset (3.3 vs. 2.0 mg/dL), lower prevalence of remission
      of NS (5% vs. 48%), and higher proteinuria at follow-up (5.1 vs. 2.5 g/day).
      Graft survival improved with NS remission (88% vs. 18%). CONCLUSION: Post-Tx NS
      displays distinctive clinicopathologic features with pathogenetic and therapeutic
      implications.

PMID- 15149350
TI  - Influence of initiation of maintenance hemodialysis on biomarkers of inflammation
      and oxidative stress.
AB  - BACKGROUND: Chronic inflammation and oxidative stress are highly prevalent in
      patients with chronic kidney disease and end-stage renal disease (ESRD). These
      conditions contribute to high mortality rates associated with cardiovascular
      disease, the leading cause of death in this patient population. To our knowledge,
      no prospective studies have examined how initiation of maintenance hemodialysis
      (MHD) affects biomarkers of inflammation and oxidative stress status. METHODS:
      This was a prospective cohort study evaluating time-dependent changes in C
      reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and protein
      carbonyl content before and after initiation of MHD over a 12-month period. Fifty
      incident hemodialysis patients [57.6 +/- 17.2 years, 60% male, 38% Caucasians,
      32% insulin-dependent diabetes mellitus (IDDM) were studied, with 50 healthy
      subjects for comparison. The study variables were assessed before the initial
      outpatient hemodialysis treatment, and every 3 months thereafter for 12 months.
      RESULTS: At baseline, CRP, IL-6, and carbonyl content levels were significantly
      higher in MHD patients compared with healthy subjects (P < 0.001 for each). After
      initiation of MHD, there were no significant changes in any of the study
      variables. Patients who initiated MHD with the highest levels of all the study
      variables had a significant decrease over the next year, but the variables were
      still higher than normal at the end of the 12-month study period. CONCLUSION: Our
      data show that initiation of MHD does not have significant influence on plasma
      concentrations of CRP, IL-6, and IL-10, as well as plasma protein carbonyl
      content. These findings suggest that MHD is ineffective in controlling
      inflammation and oxidative stress in uremia.

PMID- 15149351
TI  - Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study.
AB  - BACKGROUND: Cardiac disease is a common cause of death in chronic hemodialysis
      patients. A subanalysis of the data on cardiac diseases in the Hemodialysis
      (HEMO) Study was performed. The specific objectives were: (1) to analyze the
      prevalence of cardiac disease at baseline; (2) to characterize the incidence of
      various types of cardiac events during follow-up; (3) to examine the association
      of cardiac events during follow-up with baseline cardiac diseases; and (4) to
      examine the effect of dose and flux interventions on various types of cardiac
      events. METHODS: The HEMO Study is a randomized multi-center trial on 1846
      chronic hemodialysis patients at 15 clinical centers comprising 72 dialysis
      units. The scheduled maximum follow-up duration was 0.9 to 6.6 years, with the
      mean actual follow-up of 2.84 years. The interventions were standard-dose versus
      high-dose and low-flux versus high-flux hemodialysis in a 2 x 2 factorial design.
      RESULTS: At baseline, 80% of patients had cardiac diseases, including ischemic
      heart disease (IHD) (39%), congestive heart failure (40%), arrhythmia (31%), and
      other heart diseases (63%). There were a total of 1685 cardiac hospitalizations,
      with angina and acute myocardial infarction accounting for 42.7% of these
      hospitalizations. There were 343 cardiac deaths during follow-up, accounting for
      39.4% of all deaths. IHD was implicated in 61.5% of the cardiac deaths. Any
      cardiac disease at baseline was highly predictive of cardiac death during follow
      up [relative risk (RR) 2.57; 95% CI 1.73-3.83]. There were no significant effects
      of dose or flux assignments on the primary outcome of all-cause mortality or the
      main secondary cardiac composite outcome of first cardiac hospitalization or all
      cause mortality. Assignment to high-flux dialysis was, however, associated with
      decreased cardiac mortality and the composite outcome of first cardiac
      hospitalization or death from cardiac causes. CONCLUSION: The HEMO Study
      identified IHD to be a major cause of cardiac hospitalizations and cardiac
      deaths. Future strategies for the prevention of cardiac diseases in the
      maintenance hemodialysis population should focus on this entity. Although high
      flux dialysis did not reduce all-cause mortality, it might improve cardiac
      outcomes. This hypothesis needs to be further examined.

PMID- 15149352
TI  - Noninvasive detection of renal allograft inflammation by measurements of mRNA for
      IP-10 and CXCR3 in urine.
AB  - BACKGROUND: We explored the hypothesis that measurements of mRNA encoding
      interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in
      urinary cells offer a noninvasive means of elucidating cellular traffic causing
      acute rejection of human renal allografts. METHODS: We obtained 63 urine
      specimens from 58 renal allograft recipients who underwent 63 allograft biopsies
      to resolve the basis for graft dysfunction, and 27 additional urine samples from
      24 other patients with stable allograft function. Twenty-seven of the 63 biopsies
      were classified as acute rejection, 20 as other, and 16 as chronic allograft
      nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a
      constitutively expressed gene 18S rRNA in the urine specimens and correlated
      transcript levels with renal allograft diagnosis. RESULTS: mRNA levels of IP-10
      (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P= 0.56)
      predicted intragraft cellular traffic causing acute rejection. Receiver-operating
      characteristic curve analysis demonstrated that acute rejection can be predicted
      with a sensitivity of 100% and a specificity of 78% using the (log-transformed)
      cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a
      specificity of 83% using the cutoff value of 11.59 copies of CXCR3.
      Immunohistologic analysis of allograft biopsies showed exuberant expression of IP
      10 and CXCR3 during acute rejection whereas both were absent in grafts with
      stable function. CONCLUSION: Our investigation demonstrates that intragraft
      cellular events associated with acute rejection of human renal allografts can be
      noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary
      cells.

PMID- 15149353
TI  - Survival differences between peritoneal dialysis and hemodialysis among "large"
      ESRD patients in the United States.
AB  - BACKGROUND: It has been hypothesized that peritoneal dialysis compared to
      hemodialysis may be less effective in large patients with end-stage renal disease
      (ESRD). METHODS: We tested this hypothesis in a cohort of 134,728 new ESRD
      patients who were initiated on dialysis from May 1, 1995 to July 31, 1997 using
      data from United States Renal Data System (USRDS). Cox regression models
      evaluated the association of body mass index (BMI) in quintiles (8.8-20.9, 20.9
      23.5, 23.5-26.1, 26.1-30.0, 30.0-75.2 kg/m(2)) with mortality over 2 years in
      peritoneal dialysis and hemodialysis patients separately, while time-dependent
      models evaluated the relative risk (RR) of death by modality for each BMI
      quintile. RESULTS: For hemodialysis, the adjusted RR of death was greatest for
      patients with BMI <or = 20.9 (RR = 1.40, 95% CI 1.32-1.50 for diabetics and RR =
      1.27, 95% CI 1.21-1.34 for nondiabetics) and lowest for patients with BMI >30.0
      (RR = 0.97, 95% CI 0.96-0.99 for diabetic and RR = 0.97, 95% CI 0.95-0.98 for
      nondiabetic patients) compared with the referent (23.5-26.1; RR = 1.00). For
      peritoneal dialysis, the RR of death was also higher for patients with a BMI
      <20.9 (RR = 1.20, 95% CI 1.00-1.43 for diabetic and RR = 1.39, 95% CI 1.19-1.64
      for nondiabetic patients) but no survival advantage was associated with higher
      BMI values. The RR of death (peritoneal dialysis/hemodialysis) for each BMI
      quintile was 0.99, 1.12, 1.26 (P < 0.01), 1.15 (P < 0.01), and 1.44 (P < 0.0001)
      for diabetic and were 1.07, 1.01, 0.96, 1.04, and 1.22 (P < 0.01) for nondiabetic
      patients, respectively. CONCLUSION: We conclude that body size modifies the
      impact of dialysis modality on mortality risk among new ESRD patients in the
      United States. The selection of hemodialysis over peritoneal dialysis was
      associated with a survival advantage in patients with large body habitus.

PMID- 15149354
TI  - Immunologic risk factors and glomerular C4d deposits in chronic transplant
      glomerulopathy.
AB  - BACKGROUND: Chronic transplant glomerulopathy is an uncommon cause of chronic
      transplant dysfunction of unknown pathogenesis. We evaluated the epidemiologic,
      clinical, and histologic features of chronic transplant glomerulopathy. To
      determine the possible contribution of humoral immune responses, we assessed
      glomerular deposition of C4d. METHODS: From a cohort of 1111 kidney transplants
      (1983 to 2001) with at least 6 months of graft function, we identified 18 cases
      with chronic transplant glomerulopathy (1.6%) showing double contours of the
      glomerular basement membrane (GBM) on light microscopy. To assess the risk
      factors, this group was compared with 739 patients with stable function using
      multivariate Cox regression analysis. Paraffin sections of 11/18 biopsies were
      stained with polyclonal C4d antibodies. Sera of 13/18 patients could be tested
      for antidonor human leukocyte antigen (HLA) antibodies by enzyme-linked
      immunosorbent assay (ELISA). Patients with chronic allograft nephropathy without
      chronic transplant glomerulopathy or predominant cyclosporine nephrotoxicity were
      used as controls. RESULTS: Chronic transplant glomerulopathy was diagnosed at a
      median of 8.3 (range 2.6-12.5) years posttransplantation. Panel reactive
      antibodies at time of transplantation, RR 1.23 (1.05-1.45) per 10% increase, and
      late acute rejection episodes, RR 7.6 (1.8-31.7), were independently associated
      with chronic transplant glomerulopathy. We found glomerular C4d deposits in 10/11
      biopsies showing chronic transplant glomerulopathy and in only 2/13 controls.
      Peritubular capillary C4d deposits and donor-specific anti-HLA antibodies were
      demonstrated in 4 and 3 of the 10 patients with glomerular C4d deposits,
      respectively. CONCLUSION: Presensitization and late acute rejection episodes were
      the risk factors identified. Glomerular C4d deposits suggest that chronic
      transplant glomerulopathy emerges from in situ humoral rejection. Chronic
      transplant glomerulopathy should be considered as a manifestation of immune
      mediated injury.

PMID- 15149355
TI  - Analgesic prescription patterns among hemodialysis patients in the DOPPS:
      potential for underprescription.
AB  - BACKGROUND: Dialysis patients require special consideration regarding analgesics,
      given their altered pharmacokinetic and pharmacodynamic profiles and increased
      potential for adverse reactions. METHODS: Analgesic prescription patterns were
      investigated using data from the Dialysis Outcomes and Practice Patterns Study
      (DOPPS), with 3749 patients in 142 United States facilities studied between May
      1996 and September 2001. RESULTS: The proportion of patients prescribed any
      analgesic decreased from 30.2% to 24.3%; narcotic prescriptions decreased from
      18.0% to 14.9%. The most commonly prescribed narcotics were
      propoxyphene/acetaminophen combinations (47.2%). Combinations containing
      acetaminophen were prescribed concurrently for 84.1% of patients on narcotics.
      About one half of prescriptions for narcotics, acetaminophen, and cyclooxygenase
      2 (COX-2) agents were for 12 months or more; one half of prescriptions for
      nonsteroidal anti-inflammatory drugs (NSAIDs) were for 8 months or more. The
      proportion of patients prescribed analgesics varied by facility (mean +/- SD =
      27.9%+/- 18.9% for all analgesics, range 0% to 89.3%). Analgesic prescription was
      more likely among the elderly, women, and patients with cardiovascular disease
      (other than coronary artery disease or congestive heart failure), lung and
      psychiatric disease, cancer (other than skin), and recurrent cellulitis. Patients
      prescribed laxatives were almost twice as likely to be on a narcotic (odds ratio
      = 1.95, P < 0.0001). Analgesic prescription did not correlate with loss of
      residual renal function or hospitalization for a gastrointestinal disorder. Three
      quarters of patients reporting moderate to very severe pain were not prescribed
      analgesics. Furthermore, 74% of patients with pain that interfered with work had
      no analgesic prescription. CONCLUSION: Dialysis patients and providers may
      benefit from both refinement of existing guidelines and a renewed understanding
      regarding appropriate prescription of analgesics.

PMID- 15149356
TI  - Proteomic patterns established with capillary electrophoresis and mass
      spectrometry for diagnostic purposes.
AB  - BACKGROUND: Proteomics applied in large scale may provide a useful diagnostic
      tool. METHODS: We developed an online combination of capillary electrophoresis
      with mass spectrometry, allowing fast and sensitive evaluation of polypeptides
      found in body fluids. Utilizing this technology, polypeptide patterns from urine
      are established within 45 minutes. About 900 to 2500 polypeptides as well as
      their concentrations are detected in individual urine samples without the need
      for specific reagents such as antibodies. To test this method for clinical
      application, we examined spot urine samples from 57 healthy individuals, 16
      patients with minimal change disease (MCD), 18 patients with membranous
      glomerulonephritis (MGN), and 10 patients with focal segmental glomerulosclerosis
      (FSGS). RESULTS: One-hundred seventy-three polypeptides were present in more than
      90% of the urine samples obtained from healthy individuals, while 690
      polypeptides were present with more than 50% probability. These data permitted
      the establishment of a "normal" polypeptide pattern in healthy individuals.
      Polypeptides found in the urine of patients differed significantly from the
      normal controls. These differences allowed the distinction of specific protein
      spectra in patients with different primary renal diseases. Abnormal pattern of
      proteins were found even in urine from patients in clinical remission.
      CONCLUSION: The data indicate that capillary electrophoresis with mass
      spectrometry coupling provides a promising tool that permits fast and accurate
      identification and differentiation of protein patterns in body fluids of healthy
      and diseased individuals, thus enabling diagnosis based on these patterns.

PMID- 15149357
TI  - A systematic evaluation of bioelectrical impedance measurement after hemodialysis
      session.
AB  - BACKGROUND: There is still no definitive indication about the ideal point of time
      to perform bioimpedance analysis (BIA) in hemodialysis patients. Furthermore, the
      interpretation of data in this regard is difficult because there is still no
      comprehensive information about the fluctuations in BIA variables occurring in
      these subjects. The aim of this study was to assess BIA changes occurring in
      hemodialysis and specifically in the dry-weight state. METHODS: We studied 27
      anuric patients (20 males and 7 females; age 56.1 +/- 13.7 years) on chronic
      hemodialysis. Single-frequency BIA (R, resistance; Xc, reactance; and PhA, phase
      angle) was performed (1) before and at the end of hemodialysis (dialysis period);
      (2) 15, 30, 60, 90, and 120 minutes after hemodialysis (postdialysis period); and
      (3) 24, 48, and 68 hours after hemodialysis (interdialysis period). RESULTS: Body
      weight decreased by 2.8 +/- 0.8 kg during hemodialysis, was unchanged during the
      postdialysis period, and progressively rose during the interdialysis period. At
      the same time, BIA variables significantly increased during hemodialysis (R, 453
      +/- 74 and 542 +/- 98 ohm; Xc, 38 +/- 10 and 53 +/- 16 ohm; P < 0.05), remained
      stable over the 120-minute period after treatment (R, 538 +/- 94, 539 +/- 95, 538
      +/- 94, 541 +/- 95, and 544 +/- 95 ohm; and Xc, 53 +/- 15, 53 +/- 15, 51 +/- 16,
      52 +/- 16, and 52 +/- 16 ohm; NS), and subsequently declined [R, 471 +/- 79 (P=
      <0.05 vs. postdialysis), 449 +/- 71 (P= <0.05 vs. postdialysis), 424 +/- 68 (P=
      <0.05 vs. postdialysis) ohm; Xc, 42 +/- 13 (P= <0.05 vs. postdialysis), 37 +/- 10
      (P= <0.05 vs. postdialysis), 34 +/- 13 (P= <0.05 vs. postdialysis) ohm]. The
      stability of BIA measures during postdialysis was confirmed by the constant
      relationship found between R/height and Xc/height. Also PhA increased after
      dialysis (4.8 +/- 1.1 degrees vs. 5.7 +/- 1.3 degrees, P < 0.05), was unchanged
      during the following 120 minutes and decreased in the interdialysis period (5.1
      +/- 1.3 degrees, 4.8 +/- 1.0 degrees, and 4.5 +/- 1.1 degrees, P < 0.05). At the
      end of hemodialysis and during the postdialysis period total body water (TBW)
      estimated from BIA was similar on average to TBW calculated using Watson formulas
      (37.2 +/- 6.3 L vs. 36.2 +/- 5.7 L, NS). On the contrary, when patients were
      hyperhydrated BIA significantly overestimated the Watson's values. CONCLUSION: In
      hemodialysis patients BIA variables fluctuate to a considerable extent (with the
      highest values immediately after hemodialysis), but remain constant and highly
      reproducible over the 120 minutes after the end of hemodialysis, that is, in a
      dry-weight state. Thus, taking into consideration that the point in time chosen
      for performing BIA is crucial to properly assess body composition, BIA can be
      appropriately performed at anytime during the postdialysis period, provided that
      hydration status does not change due to food or drink consumption.

PMID- 15149358
TI  - A plethora of epidermal growth factor-like proteins in polycystic kidneys.

PMID- 15149359
TI  - Comparing methods for calculating GFR in children and adults.

PMID- 15149361
TI  - MTHFR C677T polymorphism and skin color: the white man's blackness.

PMID- 15149362
TI  - Mitochondrial causes of renal insufficiency and hearing loss.

PMID- 15149363
TI  - Gene expression analysis in microdissected renal biopsy.

PMID- 15149364
TI  - Can error in GFR formulas explain their poor performance in transplant patients?

PMID- 15149370
TI  - Anti-discrimination actions in mental health.

PMID- 15149366
TI  - When man turns to stone: extraosseous calcification in uremic patients.

PMID- 15149372
TI  - How was it for you? Families' experiences of receiving Behavioural Family
      Therapy.
AB  - The benefits of family interventions for families having to cope with serious
      mental health problems are well documented but routine implementation of these
      interventions is often problematic. Despite a wealth of research on the clinical
      outcomes of such interventions, very little is known about families' subjective
      perceptions of receiving them. This study reports the findings of a
      phenomenological enquiry into the lived experience of 10 families who received
      Behavioural Family Therapy (BFT) as part of a training initiative in the West
      Midlands Health Region of the UK. The results show that families were very
      satisfied with the intervention. They reported reductions in the levels of stress
      within the family, reduction in levels of carer burden, enhanced communication
      skills and a positive sense of empowerment. They attributed these changes to
      receiving BFT. The majority of families viewed mental health professionals and
      services more favourably compared to their experiences before receiving BFT. This
      is an important finding for service providers, commissioners and mental heath
      workers.

PMID- 15149371
TI  - Listening to young voices: challenges of research with adolescent mental health
      service users.
AB  - Young people who have mental health problems and use the mental health services
      need to be consulted about their views regarding their experiences of care and
      treatment in the same way as adults do. Doing research with children and young
      people is relatively new but it is becoming more common and recent literature
      highlights a need to balance respect for their voices with responsibility for
      their best interests. This can be achieved by paying close attention to ethical
      and methodological issues throughout the course of every study. This paper
      reviews some of the issues involved in consultation research with adolescent
      mental health service users, and illustrates them with examples taken from an
      ongoing study into the experiences of young people in three Scottish child and
      adolescent mental health services.

PMID- 15149373
TI  - Patients' experiences of being helped in an inpatient setting.
AB  - The purpose of this article is to describe patients' experiences of being helped
      during a period of psychiatric hospital care. Psychosis has traditionally been
      defined in medical and psychological terminology. The focus of psychiatric
      nursing is the human experience of distress associated with mental illness. The
      aim of psychiatric care is to promote healing and coping in daily life through
      support, validation and understanding. The main aim is to re-empower the patient
      with psychosis by using psychiatric care. The purposive sample consisted of
      interviews with nine voluntary patients recovering from psychosis. The
      interviewees told about their experiences of care. The verbatim transcripts were
      analysed using Giorgi's phenomenological method. Patients experienced care as
      helpful but unstructured: care facilitated their situation by alleviating the
      disorders, but it had not been defined by nurses, and the patients made their own
      conclusions about what care should be like. The care did not reach the inner
      world of the patients with psychosis. From the patients' point of view, care
      should protect them from vulnerability and empower/restructure their selves for
      coping in daily life.

PMID- 15149374
TI  - Seclusion: the inside story.
AB  - The objective of this study was to gain a better understanding of the seclusion
      room experiences of chronic psychiatric patients, the way in which they cope with
      their seclusion room experience, and the effect of seclusion on subsequent
      relations with care providers. A qualitative research design was used, in line
      with the procedure of Grounded Theory. Semi-structured interviews were held with
      seven chronic psychiatric outpatients whose seclusion took place at a certain
      remove in time. The transcriptions were analyzed with the aid of Winmax. The
      following results were found. Most seclusion experiences by far are negative.
      However, patients whose experience took place a considerable time ago also
      mention positive experiences. It is hard to come to terms with the seclusion
      experience; this is a matter of learning to live with it (adaptation) rather than
      assimilating it (adjustment, or active coping and controlling). Factors conducive
      to the coping process are: understanding the reason why it took place, time,
      distraction, possibilities to discuss it with others, and quick recovery of
      control. Factors prohibitive to the coping process are: the danger of recurrence,
      iniquitous treatment by care providers during seclusion, confrontation with
      others being secluded, and lack of opportunity to talk about it. Seclusion does
      not affect subsequent relation with care providers, with two exceptions. When
      patients feel they have been treated iniquitously during seclusion, or when
      seclusion continues to be a daily threat, this has a negative effect on relations
      with care providers. The central themes of this study are autonomy, trust, and
      loneliness.

PMID- 15149375
TI  - Struggling for hopefulness: a qualitative study of Swedish women who self-harm.
AB  - There has been an increase in the number of Swedish psychiatric patients who self
      harm, yet self-harm is seldom described in published research. The aim of this
      study was to describe how people who self-harm experience received care and their
      desired care. Nine participants, all Swedish women who had been treated for
      inpatient or outpatient psychiatric care, narrated their experiences of care for
      self-harm. Using qualitative content analysis, two themes were formulated:
      'Expecting to be confirmed while being confirmed fosters hopefulness'; and,
      'Expecting to be confirmed while not being confirmed stifles hopefulness'. Each
      of these themes emerged from five subthemes that clustered around positive and
      negative aspects of being seen-not being seen, being valued-being stigmatized,
      being connected-disconnected, being believed-doubted, and being understood-not
      being understood. Of significance is for nurses to view persons who self-harm as
      human beings and to grasp the importance of being confirmed by staff that can
      foster hopefulness in persons who self-harm, yet realize the possibility of the
      paradoxical nature of hopefulness and being confirmed.

PMID- 15149376
TI  - The user perspective: respected or rejected in mental health care?
AB  - The purpose of this study was to examine the extent to which patient views
      influence treatment planning by measuring the level of agreement between patients
      and health workers regarding patient needs as well as the impact of patient
      wishes on decision making when viewpoints conflict. Data on patient
      characteristics and needs were collected for a sample of 1080 patients within
      Norwegian mental health care using patient interviews and health worker ratings.
      Results of the assessment were then reviewed by multidisciplinary treatment teams
      responsible for making decisions regarding patient needs for services. On
      average, patients, health workers, and teams identified 4.3 (SD = 4.2), 9.3 (SD =
      5.5), and 10.3 (SD = 5.7), respectively, of 40 possible needs per patient. In
      cases where patient and health workers disagreed on the presence of a need, the
      teams tended to concur with the health worker. Interestingly, health care workers
      and teams were far more inclined than their patients to identify needs related to
      professional monitoring and follow-up. Results may indicate that contemporary
      tenets in mental health care regarding user involvement and autonomy are not
      sufficiently emphasized in practice.

PMID- 15149377
TI  - Mastery in patients with schizophrenia living in the community: relationship to
      sociodemographic and clinical characteristics, needs for care and support, and
      social network.
AB  - In line with user involvement and empowerment in individuals who suffer from a
      severe mental illness, the sense of mastery is important. Few studies have
      investigated factors that contribute to mastery in individuals with
      schizophrenia. The aims of the present 18-month follow-up study were to
      investigate associations between mastery and clinical and sociodemographic
      factors, needs for care and support and social network, and to investigate
      whether changes in mastery were related to changes with regard to these aspects
      in a group of patients (n = 120) with schizophrenia living in the community.
      Structural interviews were performed at baseline and after 18 months. Pearlin's
      mastery scale, the Camberwell Assessment of Needs (CAN), the Interview Schedule
      for Social Interaction (ISSI), and the Brief Psychiatric Rating Scale (BPRS) were
      used on both interview occasions. A stepwise regression analysis showed a
      negative relationship between psychopathology, especially affective and negative
      symptoms, and mastery. Stronger mastery was associated with younger age and less
      severe basic needs. In total psychopathology, age and basic needs explained 50.7%
      of the variance in mastery. Changes in mastery were positively correlated to
      changes in access to social contact but negatively correlated to changes in
      affective symptoms. In order to target mastery in individuals with schizophrenia,
      the community-based nursing services need to develop, implement, and evaluate
      interventions that are effective for psychiatric symptoms, social skills
      performance, and needs for care and support in areas of living, nutrition, and
      daytime activities.

PMID- 15149378
TI  - Building a case for understanding the lived experiences of males who attempt
      suicide in Alberta, Canada.
AB  - Suicide is a serious public health concern in Alberta, with, on average, over 400
      Albertans taking their own lives annually. The case for concern is even more
      pronounced when one considers that for younger Albertans (those aged less than 45
      years), suicide is the second leading cause of death. While trends in rates of
      suicide fluctuate over time, it is important to note that suicide rates for males
      have been at least three times higher than the corresponding rates for females
      since the 1950s. Furthermore, these differences have increased so that, by the
      1990s the rate for male suicide was four times higher than that of females. In
      addition, rates are increasing at a faster pace in younger cohorts. Despite the
      existence of numerous positivistically orientated studies, and the introduction
      of a range of strategies to help prevent suicide, significant reductions in
      suicide rates have not been achieved. Similarly, while there is a substantial
      literature on the issue of suicide in Canada, there remain many gaps in our
      knowledge. Our understanding of the experiences and the meanings attributed to
      these experiences that motivate contemporary Albertan males to attempt suicide is
      far from complete. In order to design interventions to help reduce the suicide
      rate, whether these are interventions at the preprimary, primary or secondary
      level of care, it is necessary to gain a more detailed and comprehensive
      understanding of this highly complex behaviour. Consequently, there is an urgent
      need to better understand the particular life experiences and the meanings that
      individuals attach to these experiences. Accordingly, this paper makes the case
      for the use of hermeneutic, phenomenological investigations, as a means to
      further elucidate the lived experiences of suicidal Alberta males.

PMID- 15149379
TI  - Mental health service user involvement in England: lessons from history.
AB  - This historical analysis draws attention to differing assumptions, which promote
      or limit user involvement in nursing practice. The meaning of the term 'user
      involvement' is analyzed with reference to varying models. A continuum is offered
      to illustrate the relationship between assumptions about people with mental
      health problems and their involvement in care. It is argued that the range of
      views concerning recipients of mental health services, from being dangerous and
      irrational to being considered equal partners with health professionals, creates
      an unresolved tension that has existed through the ages. The key to resolving
      this tension is for all parties openly to acknowledge conflicts between their
      views and those of others and engage in meaningful dialogue about them. In this
      way the lessons from history may be learned.

PMID- 15149380
TI  - Treating first episode psychosis--the service users' perspective: a focus group
      evaluation.
AB  - UK national guidance has prioritized developing specialist services for first
      episode psychosis. Such services are in the early stages of development and a
      definitive treatment model has yet to be established. The aim of this study was
      to explore service users' experiences of a first episode intervention designed
      along evidence-based 'best practice' guidelines and to establish specific
      elements seen as effective to help inform future service planning and provision.
      Twelve users of a specialist first episode service participated in focus groups.
      These were then analyzed using Interpretative Phenomenological Analysis, a
      specialized form of content analysis. Key elements identified by the service
      users included the 'human' approach as a key to the recovery process, being
      involved in treatment decisions, flexibility of appointments, high nurse to
      patient ratio, reduction in psychotic symptoms, increased confidence and
      independence and the provision of daily structure. To our knowledge, this is the
      first systematic qualitative evaluation of users' experience of a specialist
      first episode treatment intervention. Our findings indicate that adherence to
      best practice guidelines was appreciated. Regular focus groups provide a
      continuous audit cycle incorporating service improvements in line with government
      recommendations, centrally informed by the service users' and caregivers'
      perspective.

PMID- 15149381
TI  - Never good enough--part 1: Shame or borderline personality disorder?
AB  - This paper takes a deconstructive approach to the historical, clinical, and
      social context of the diagnosis of borderline personality disorder (BPD). This is
      undertaken by providing an overview of pertinent literature, an examination of
      the diagnostic criteria, a discussion of the development of the shame affect, a
      discussion of women's narratives and a reinterpretation of the symptoms of BPD as
      an overwhelming shame response. An argument is developed that shame is an
      integral but neglected feature in the experiences of mental distress that are
      characteristic of BPD. This discussion is supported with evidence of shame in
      narrative quotes from women with a diagnosis of BPD. There are striking
      similarities between what is currently pathologized as BPD and an overwhelming
      shame response. Recognizing the influence of shame may assist mental health
      nurses to provide mental health nursing care that best meets the needs of women
      experiencing these symptoms.

PMID- 15149382
TI  - Never good enough--part 2: Clinical implications.
AB  - This paper is the second part of two papers that explore the affect of shame and
      its role in the manifestation of symptoms that could be regarded as evidence of
      mental disorder. The clinical implications for nursing a person with an
      overwhelming shame response are discussed in this paper. It is proposed that a
      discursive approach to nursing care may assist mental health nurses to provide
      care that best meets the needs of people experiencing these symptoms. The paper
      suggests that this nursing care involves recognizing the impact of shame; making
      connections between how the person has learned to cope with shame and their
      current mental distress; situating shame in its socio-cultural context; focusing
      on subject-object differentiation and promoting acceptance of difference and
      exploring alternative subject positions for managing feelings of shame. The focus
      of these interventions is to encourage awareness of interactions with others, how
      the person positions her or his self in relation to others, and the communication
      patterns that perpetuate feelings of shame. It also involves helping the person
      to integrate the ideal image of her or his self with subject positions that are
      more flexible.

PMID- 15149383
TI  - Patient and nurse accounts of violent incidents in a medium secure unit.
AB  - Most studies examining violence in a forensic setting have adopted a statistical
      approach to associate relevant predictors and the likelihood of violence. Views
      of patients and nurses have been a relatively neglected research area. This study
      explored patients' and nurses' accounts of violent incidents, considering
      similarities and differences in their narratives. Permission was obtained from
      the local National Health Service Research Ethics Board and the Research Ethics
      Committee of University of East London. Anonymized transcripts were produced from
      semi-structured interviews conducted in a Medium Secure Unit with four nurses and
      four patients, who consented to talk at length with the first author about
      violent events they had witnessed on the Unit. Grounded theory analysis of the
      data generated a core category, 'control', and five constituent themes: the
      construction of identity of the perpetrator of violence; nurses' dual role of
      caring and controlling; aspects of parentalism involved in control; following set
      policies and procedures; and segregation from mainstream society. Because of
      widespread social interest and media coverage in the topic, discursive
      examination was made of aspects of social context arising within the data. This
      study was small scale and exploratory, and further confirmatory research is
      needed. Nevertheless, clear contrasts between the nurse and patient accounts
      indicated tentative suggestions for training (including user involvement) and
      intervention in managing violent behaviour.

PMID- 15149384
TI  - Mental health practice and the rhetoric-reality gap.
AB  - This paper had its genesis in a national project, sponsored by the English
      National Board for Nursing, Midwifery and Health Visiting, to explore team
      working within mental health practice. The project extended over a 2-year period
      and utilized various methods of data collection. However, this paper focused on
      data, from the national survey and informal interviews (based in eight regions),
      that addressed specific issues within the practitioner group. Of the 800
      questionnaires sent out 26% were returned. Fifty-three percent of the returns
      were from practitioners, 14% user/carers and 33% educationalists. Our focus was
      that of the practitioners. This group had a response rate of 50% (i.e. 50% of the
      surveys sent out to practitioners were returned). A content analysis of 100
      interviews was used to triangulate the data. Whilst the original brief was to
      explore team working the survey also highlighted data that indicated a common
      understanding of what mental health practitioners do and what they say they do
      and that, although there was a commonality of vocabulary, different practices
      existed between and within regions. This is the focus of this paper. We argue,
      from our findings, that different practice is a result of 'habitus'. Whilst
      practitioners reported that they subscribe to a national agreement of meaning,
      there is a rhetoric-reality gap: that which is said to be done is not what is, in
      fact, practised. At the local level we argue that working within the habitus
      (educationally) can address the rhetoric-reality gap. However, we recommend
      further studies in order to explore how working within the habitus can address
      this matter across regions.

PMID- 15149385
TI  - Putting it all together: dealing with complexity in the understanding of the
      human condition.
AB  - In this paper, two mental health nurses who have experienced long academic
      careers reflect on the way their own thinking and teaching about the human
      condition has changed over the course of their careers. Three major paradigms
      that have attempted to explain the human condition, the biological sciences,
      psychodynamic theory, and socio-cultural theory, are discussed. It is argued that
      no single approach is sufficient to address the complexities of providing care
      within psychiatric and mental health nursing. It is further argued that the
      integration of these perspectives has not been well considered or articulated in
      practice. The authors conclude that the arguments presented in this paper are
      likely to challenge people's loyalties to a particular perspective of the human
      condition.

PMID- 15149386
TI  - Reframing the nurse's role through a social model approach: a rights-based
      approach to workers' development.

PMID- 15149387
TI  - Our experience of collaborative research: Service users, carers and researchers
      work together to evaluate an assertive outreach service.

PMID- 15149390
TI  - Levels of inbreeding depression over seven generations of selfing in the
      androdioecious clam shrimp, Eulimnadia texana.
AB  - Androdioecy (mixtures of males and hermaphrodites) is a rare mating system in
      both plants and animals. Theory suggests that high levels of inbreeding
      depression can maintain males in androdioecious populations if hermaphrodites
      commonly self-fertilize. However, if inbreeding depression (delta) can be
      'purged' from selfing populations, maintaining males is more difficult. In the
      androdioecious clam shrimp, Eulimnadia texana, delta is estimated to be as high
      as 0.7. Previous work suggests that this high level is maintained in the face of
      high levels of inbreeding due to an associative overdominance of fitness-related
      loci with the sex-determining locus. Such associative overdominance would make
      purging of inbreeding depression difficult to impossible. The current experiment
      was designed to determine if delta can be purged in these shrimp by tracking
      fitness across seven generations in selfing and outcrossing treatments. Evidence
      of purging was found in one of four populations, but the remaining populations
      demonstrated a consistent pattern of delta across generations. Although the
      experimental design allowed ample opportunity for purging, the majority of
      populations were unable to purge their genetic load. Therefore, delta in this
      species is likely due to associative overdominance caused by deleterious
      recessive alleles linked to the sex determining locus.

PMID- 15149391
TI  - Between-year variation of MHC allele frequencies in great reed warblers:
      selection or drift?
AB  - The major histocompatibility complex (MHC) genes are extremely polymorphic and
      this variation is assumed to be maintained by balancing selection. Cyclic
      interactions between pathogens and their hosts could generate such selection, and
      specific MHC alleles or heterozygosity at certain MHC loci have been shown to
      confer resistance against particular pathogens. Here we compare the temporal
      variation in allele frequencies of 23 MHC class I alleles with that of 23 neutral
      microsatellite markers in adult great reed warblers (a passerine bird) in nine
      successive cohorts. Overall, the MHC alleles showed a significantly higher
      variation in allele frequencies between cohorts than the microsatellite alleles,
      using a multi-variate genetic analysis (amova). The frequency of two specific MHC
      alleles, A3e (P = 0.046) and B4b (P = 0.0018), varied more between cohorts than
      expected from random, whereas none of the microsatellite alleles showed
      fluctuations exceeding the expectation from stochastic variation. These results
      imply that the variation in MHC allele frequencies between cohorts is not a
      result of demographic events, but rather an effect of selection favouring
      different MHC alleles in different years.

PMID- 15149392
TI  - An analysis of genetic differentiation among assortatively mating Drosophila
      melanogaster in Zimbabwe.
AB  - African Drosophila melanogaster populations, and those from Zimbabwe in
      particular, have attracted much interest recently. African flies differ
      genetically from 'cosmopolitan' populations and were found to exhibit
      discriminative mating behaviour against individuals from 'cosmopolitan'
      populations. It has therefore been proposed that Zimbabwean and some other
      African populations are in an 'incipient stage of speciation'. However, whether
      the mating behaviour is an effective barrier against gene flow from other
      populations, and whether intra-population genetic differentiation has already
      evolved in sympatry is not known. Here, we took a population-based approach to
      test whether the well-characterized mating type differences have resulted in a
      genome-wide differentiation at the population level. Using 122 polymorphic
      microsatellite loci mapping to the third chromosome, we demonstrate a significant
      genetic differentiation between Zimbabwean flies differing in their mating
      behaviour. We also provide evidence to suggest that this difference is unlikely
      to be attributable to population structure within Zimbabwe. However, the analysis
      of individual microsatellite loci did not indicate more loci differentiating
      these two groups than expected by chance. Our data suggest that the 'Z'-'M'
      mating behaviour is strong enough to result in a small but significant genetic
      differentiation. Thus, future studies based on a larger population sample of
      flies characterized for their mating behaviour and using more markers are
      expected to provide more information on the genetic basis of the mating traits in
      the Zimbabwe flies.

PMID- 15149393
TI  - Effects of egg yolk testosterone on growth and immunity in a precocial bird.
AB  - In oviparous vertebrates, maternal steroid allocation to eggs can have important
      fitness consequences for the offspring. However, elevated testosterone levels are
      not only associated with beneficial postnatal effects, such as enhanced growth
      and high social status, but may also entail costs by suppressing the immune
      system. In this study, testosterone levels in eggs of Chinese painted quail
      (Coturnix chinensis) were experimentally manipulated to evaluate its effects on
      growth and immunocompetence. Testosterone did not affect embryonic development,
      body size or growth during the first 20 days. However, elevated testosterone
      levels during embryonic development were immunosuppressive for chicks with
      inherently higher growth rate. Adaptive scenarios where only beneficial effects
      of increased testosterone levels are considered may therefore need to be re
      evaluated.

PMID- 15149394
TI  - Plant-like mating in an animal: sexual compatibility and allocation trade-offs in
      a simultaneous hermaphrodite with remote transfer of sperm.
AB  - The importance of sexual compatibility between mates has only recently been
      realized in zoological research into sexual selection, yet its study has been
      central to botanical research for many decades. The reproductive characteristics
      of remote mating, an absence of precopulatory mate screening, internal
      fertilization and embryonic brooding are shared between passively pollinated
      plants and a phylogenetically diverse group of sessile aquatic invertebrates.
      Here, we further characterize the sexual compatibility system of one such
      invertebrate, the colonial ascidian Diplosoma listerianum. All 66 reciprocal
      pairings of 12 genetic individuals were carried out. Fecundities of crosses
      varied widely and suggested a continuous scale of sexual compatibility. Of the 11
      animals from the same population c. 40% of crosses were completely incompatible
      with a further c. 20% having obvious partial compatibility (reduced fecundity).
      We are unaware of other studies documenting such high levels of sexual
      incompatibility in unrelated individuals. RAPD fingerprinting was used to
      estimate relatedness among the 12 individuals after a known pedigree was
      successfully reconstructed to validate the technique. In contrast to previous
      results, no correlation between genetic similarity and sexual compatibility was
      detected. The blocking of many genotypes of sperm is expected to severely modify
      realized paternity away from 'fair raffle' expectations and probably reduce
      levels of intra-brood genetic diversity in this obligatorily promiscuous mating
      system. One adaptive benefit may be to reduce the bombardment of the female
      reproductive system by outcrossed sperm with conflicting evolutionary interests,
      so as to maintain female control of somatic : gametic investment.

PMID- 15149395
TI  - Parasites make male pipefish careless.
AB  - Parasite-mediated sexual selection is expected to favour the avoidance of matings
      with infected individuals. However, the extent to which the costs and benefits of
      discriminating against parasitized mates trade off may depend upon numerous
      factors. I investigated the effects of sex and infection status on choosiness in
      sex-role reversed deep-snouted pipefish (Syngnathus typhle L.) that were either
      artificially infected with the trematode parasite Cryptocotyle sp. or sham
      infected. Sham-infected males were significantly more likely to associate with a
      sham-infected female rather than with a Cryptocotyle-infected female. Infected
      males failed to discriminate against infected potential partners. Males were
      choosier the larger they were relative to the females available for choice.
      Females were not discriminatory, regardless of their infection status. Given an
      inverse relation between female fecundity and parasite load, choosy unparasitized
      males may gain enhanced reproductive success from their choice decisions. In
      contrast, more heavily infected wild-caught males gave birth to slightly fewer,
      but not smaller offspring than did uninfected or lightly infected males,
      suggesting only a low direct premium on choosy females. The detrimental effects
      of parasitism on male choosiness, and the lack of female discrimination against
      infected males likely have profound repercussions on the strength of sexual
      selection acting on the two sexes and on the dynamics of host-parasite
      interactions in this system.

PMID- 15149396
TI  - Mutation-selection balance accounting for genetic variation for viability in
      Drosophila melanogaster as deduced from an inbreeding and artificial selection
      experiment.
AB  - We carried out an experiment of inbreeding and upward artificial selection for
      egg-to-adult viability in a recently captured population of Drosophila
      melanogaster, as well as computer simulations of the experimental design, in
      order to obtain information on the nature of genetic variation for this important
      fitness component. The inbreeding depression was linear with a rate of 0.70 +/-
      0.11% of the initial mean per 1% increase in inbreeding coefficient, and the
      realized heritability was 0.06 +/- 0.07. We compared the empirical observations
      of inbreeding depression and selection response with computer simulations
      assuming a balance between the occurrence of partially recessive deleterious
      mutations and their elimination by selection. Our results suggest that a model
      assuming mutation-selection balance with realistic mutational parameters can
      explain the genetic variation for viability in the natural population studied.
      Several mutational models are incompatible with some observations and can be
      discarded. Mutational models assuming a low rate of mutations of large average
      effect and highly recessive gene action, and others assuming a high rate of
      mutations of small average effect and close to additive gene action, are
      compatible with all the observations.

PMID- 15149397
TI  - Human birthweight evolution across contrasting environments.
AB  - We explore from both theoretical and empirical perspectives the hypothesis that a
      significant part of the worldwide variability in human birthweight results from
      adaptive responses to local selective pressures. We first developed an agent
      based model to simulate the process of evolutionary selection on life history
      strategy, and then we performed a comparative analysis across 89 countries
      worldwide. The model illustrates that optimal birthweight depends on which
      fitness-reducing risk locally predominates (somatic diseases, parasitic diseases
      or adverse environmental conditions). When fitness variations between individuals
      mainly result from somatic diseases (e.g. industrialized countries), or
      conversely from infectious and parasitic diseases (e.g. developing countries),
      selection is expected to favour individuals producing larger children.
      Conversely, when environmental risks increase in relative importance, selective
      pressures for producing children with high birthweight are reduced. The
      comparative analysis supports these theoretical expectations, in particular the
      finding that birthweight is higher than predicted in highly parasitized
      countries.

PMID- 15149398
TI  - Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis
      lyrata.
AB  - Self-incompatibility in Arabidopsis lyrata is sporophytically controlled by the
      multi-allelic S-locus. Self-incompatibility alleles (S-alleles) are under strong
      negative frequency dependent selection because pollen carrying common S-alleles
      have fewer mating opportunities. Population genetics theory predicts that
      deleterious alleles can accumulate if linked to the S-locus. This was tested by
      studying segregation of S-alleles in 11 large full sib families in A. lyrata.
      Significant segregation distortion leading to an up to fourfold difference in
      transmission rates was found in six families. Differences in transmission rates
      were not significantly different in reciprocal crosses and the distortions
      observed were compatible with selection acting at the gametic stage alone. The S
      allele with the largest segregation advantage is also the most recessive, and is
      very common in natural populations concordant with its apparent segregation
      advantage. These results imply that frequencies of S-alleles in populations of A.
      lyrata cannot be predicted based on simple models of frequency-dependent
      selection alone.

PMID- 15149399
TI  - Modelling the establishment and spread of autotetraploid plants in a spatially
      heterogeneous environment.
AB  - The establishment and spread of autotetraploids from an original diploid
      population in a heterogeneous environment were studied using a stochastic
      simulation model. Specifically, we investigated the effects of heterogeneous
      habitats and nonrandom pollen/seed dispersal on the critical value (micro) of
      unreduced 2n gamete production necessary for the establishment of autotetraploids
      as predicted by deterministic models. Introduction of a heterogeneous environment
      with random pollen/seed dispersal had little effect on the micro value. In
      contrast, incorporating nonrandom pollen/seed dispersal into a homogeneous
      environment considerably reduced the micro value. Incorporating both
      heterogeneous habitats and nonrandom pollen/seed dispersal may lead either to an
      increase or to a decrease in the micro value compared to that with random
      dispersal, indicating that the two factors interact in a complex way.

PMID- 15149400
TI  - Social group size, potential sperm competition and reproductive investment in a
      hermaphroditic leech, Helobdella papillornata (Euhirudinea: Glossiphoniidae).
AB  - Social group size may affect the potential for sperm competition, and this in
      turn may favour ontogenetic adjustments in testicular mass according to the
      likely requirements for sperm and spermatophore production. In a number of
      comparative analyses of testis mass among vertebrate species that differ in
      mating system or social organization, increasing potential for sperm competition
      is associated with larger testis size. Intraspecific phenotypic plasticity should
      be able to produce the same pattern if social group size is heterogenous and
      reflects differing degrees of average sperm competition, but this intraspecific
      effect is less well studied. We tested the effect of social groups on both male
      and female investment in the simultaneously hermaphroditic leech, Helobdella
      papillornata. Leeches were placed in groups of one, two, four or eight. Sexual
      investment at the onset of reproductive maturity was quantified as the total
      testisac volume for male function and total egg volume for female function. We
      found that testisac volume (statistically adjusted for body size) showed a
      significant increase with increasing group size. Total egg volume (also adjusted
      for body size) was unaffected by group size. Our findings indicate adaptive
      developmental plasticity in male gonad investment in response to the potential
      for sperm competition.

PMID- 15149401
TI  - Trade-offs between sexual and clonal reproduction in an aquatic plant:
      experimental manipulations vs. phenotypic correlations.
AB  - That trade-offs result from the allocation of limited resources is a central
      concept of life history evolution. We quantified trade-offs between sexual and
      clonal reproduction in the aquatic plant, Butomus umbellatus, by experimentally
      manipulating sexual investment in two distinct nutrient environments. Increasing
      seed production caused a significant but nonlinear trade-off. Pollinating half of
      all flowers strongly reduced clonal bulbil production, but pollinating the
      remaining flowers did not cause any further trade-off. Trade-offs were not
      stronger under low nutrient conditions that clearly limited plant growth.
      Experimentally induced trade-offs were not reflected in negative phenotypic
      correlations between sexual and clonal allocation among plants within eight
      populations grown in a uniform greenhouse environment. Diminishing effects of
      increased sexual allocation plus a lack of accord between experimental
      manipulations and phenotypic correlations suggest that trade-offs between sexual
      and clonal reproduction are unlikely to constrain the evolution of reproductive
      strategy in this species.

PMID- 15149402
TI  - Epistasis affecting litter size in mice.
AB  - Litter size is an important reproductive trait as it makes a major contribution
      to fitness. Generally, traits closely related to fitness show low heritability
      perhaps because of the corrosive effects of directional natural selection on the
      additive genetic variance. Nonetheless, low heritability does not imply,
      necessarily, a complete absence of genetic variation because genetic interactions
      (epistasis and dominance) contribute to variation in traits displaying strong
      heterosis in crosses, such as litter size. In our study, we investigated the
      genetic architecture of litter size in 166 females from an F2 intercross of the
      SM/J and LG/J inbred mouse strains. Litter size had a low heritability (h2 = 12%)
      and a low repeatability (r = 33%). Using interval-mapping methods, we located two
      quantitative trait loci (QTL) affecting litter size at locations D7Mit21 + 0 cM
      and D12Mit6 + 8 cM, on chromosomes 7 and 12 respectively. These QTL accounted for
      12.6% of the variance in litter size. In a two-way genome-wide epistasis scan we
      found eight QTL interacting epistatically involving chromosomes 2, 4, 5, 11, 14,
      15 and 18. Taken together, the QTL and their interactions explain nearly 49%
      (39.5% adjusted multiple r2) of the phenotypic variation for litter size in this
      cross, an increase of 36% over the direct effects of the QTL. This indicates the
      importance of epistasis as a component of the genetic architecture of litter size
      and fitness in our intercross population.

PMID- 15149403
TI  - Parasitism, host immune defence and dispersal.
AB  - Host-parasite interactions have been hypothesized to affect the evolution of
      dispersal by providing a possibility for hosts to escape debilitating parasites,
      and by influencing the level of local adaptation. We used a comparative approach
      to investigate the relationship between a component of host immune function
      (which reflects the evolutionary history of parasite-induced natural selection)
      and dispersal in birds. We used a sample of 46 species of birds for which we had
      obtained field estimates of T-cell response for nestlings, mainly from our own
      field studies in Denmark and Spain. Bird species with longer natal, but not with
      longer breeding dispersal distances had a stronger mean T-cell-mediated immune
      response in nestlings than species with short dispersal distances. That was also
      the case when controlling for the potentially confounding effect of migration
      from breeding to wintering area, which is known from previous studies to be
      positively associated with dispersal distance. These relationships held even when
      controlling for similarity among species because of common ancestry. Avian hosts
      with a larger number of different breeding habitats had weaker mean T-cell
      mediated immune responses than habitat specialists. This relationship held even
      when controlling for similarity among species because of common ancestry.
      Therefore, T-cell-mediated immunity is an important predictor of evolutionary
      changes in dispersal ability among common European birds.

PMID- 15149404
TI  - The evolution of phenotypic plasticity in spatially structured environments:
      implications of intraspecific competition, plasticity costs and environmental
      characteristics.
AB  - We model the evolution of reaction norms focusing on three aspects: frequency
      dependent selection arising from resource competition, maintenance and production
      costs of phenotypic plasticity, and three characteristics of environmental
      heterogeneity (frequency of environments, their intrinsic carrying capacity and
      the sensitivity to phenotypic maladaptation in these environments). We show that
      (i) reaction norms evolve so as to trade adaptation for acquiring resources
      against cost avoidance; (ii) maintenance costs cause reaction norms to better
      adapt to frequent rather than to infrequent environments, whereas production
      costs do not; and (iii) evolved reaction norms confer better adaptation to
      environments with low rather than with high intrinsic carrying capacity. The two
      previous findings contradict earlier theoretical results and originate from two
      previously unexplored features that are included in our model. First, production
      costs of phenotypic plasticity are only incurred when a given phenotype is
      actually produced. Therefore, they are proportional to the frequency of
      environments, and these frequencies thus affect the selection pressure to avoid
      costs just as much as the selection pressure to improve adaptation. This prevents
      the frequency of environments from affecting the evolving reaction norm.
      Secondly, our model describes the evolution of plasticity for a phenotype
      determining an individual's capability to acquire resources, and thus its
      realized carrying capacity. When individuals are distributed randomly across
      environments, they cannot avoid experiencing environments with intrinsically low
      carrying capacity. As selection pressures arising from the need to improve
      adaptation are stronger under such extreme conditions than under mild ones,
      better adaptation to environments with low rather than with high intrinsic
      carrying capacity results.

PMID- 15149405
TI  - Sexual selection on morphological and physiological traits and fluctuating
      asymmetry in the black scavenger fly Sepsis cynipsea.
AB  - Previous univariate studies of the fly Sepsis cynipsea (Diptera: Sepsidae) have
      demonstrated spatiotemporally variable and consequently overall weak sexual
      selection favouring large male size, which is nevertheless stronger on average
      than fecundity selection favouring larger females. To identify specific target(s)
      of selection on body size and additional traits possibly affecting mating
      success, two multivariate field studies of sexual selection were conducted. In
      one study using seasonal replicates from three populations, we assessed 15
      morphological traits. No clear targets of sexual selection on male size could be
      detected, perhaps because spatiotemporal variation in selection was again strong.
      In particular, there was no (current) selection on male abdomen length or fore
      coxa length, the only traits for which S. cynipsea males are not smaller than
      females. Interestingly, copulating males had a consistently shorter fore femur
      base, a secondary sexual trait, and a wider clasper (hypopygium) gap, an external
      genital trait. In a second study using daily and seasonal replicates from one
      population, we included physiological measures of energy reserves (lipids,
      glucose, glycogen), in addition to hind tibia length and fluctuating asymmetry
      (FA) of all pairs of legs. This study again confirmed the mating advantage of
      large males, and additionally suggests independent positive influences of lipids
      (the long-term energy stores), with effects of glucose and glycogen (the short
      term energy stores) tending to be negative. FA of paired traits was not
      associated with male mating success. Our study suggests that inclusion of
      physiological measures and genital traits in phenomenological studies of
      selection, which is rare, would be fruitful in other species.

PMID- 15149406
TI  - Variable selection in Platanthera bifolia (Orchidaceae): phenotypic selection
      differed between sex functions in a drought year.
AB  - We estimated selection on three morphological characters in the hermaphroditic,
      hawkmoth-pollinated orchid Platanthera bifolia and explored selection surfaces
      through male and female function. The work was carried out in northern Sweden
      during two flowering seasons (1994 and 1995) in one natural population and one
      season (1995) in another natural population. Fitness was estimated as number of
      pollinia removed (male function) and number of fruits produced (female function).
      We detected directional selection towards larger inflorescence size (flower
      number) through both sex functions in both populations in 1995. In 1994, with an
      unusually dry growing season, 78% of the individuals failed to set any fruit, and
      there was selection for larger inflorescences only through male function. In this
      year, there was selection towards longer flower spurs, which could be a direct or
      indirect effect of spurs being shortened by drought. The results demonstrate that
      selection patterns may vary temporally and spatially, and that the 'male function
      hypothesis' may be applicable as female function is more resource dependent than
      male function.

PMID- 15149407
TI  - The accumulation of deleterious mutations within the frozen niche variation
      hypothesis.
AB  - The frozen niche variation hypothesis proposes that asexual clones exploit a
      fraction of a total resource niche available to the sexual population from which
      they arise. Differences in niche breadth may allow a period of coexistence
      between a sexual population and the faster reproducing asexual clones. Here, we
      model the longer term threat to the persistence of the sexual population from an
      accumulation of clonal diversity, balanced by the cost to the asexual population
      resulting from a faster rate of accumulation of deleterious mutations. We use
      Monte-Carlo simulations to quantify the interaction of niche breadth with
      accumulating deleterious mutations. These two mechanisms may act synergistically
      to prevent the extinction of the sexual population, given: (1) sufficient genetic
      variation, and consequently niche breadth, in the sexual population; (2) a
      relatively slow rate of accumulation of genetic diversity in the clonal
      population; (3) synergistic epistasis in the accumulation of deleterious
      mutations.

PMID- 15149408
TI  - Extra-nuclear effects on growth and development in the sand cricket Gryllus
      firmus.
AB  - Although largely ignored until recently, parental effects on the phenotypes of
      their offspring are both ubiquitous in nature and of a potentially great
      importance to evolution. Our study examines the presence of extra-nuclear
      (maternal and paternal) effects in growth traits, development time and adult size
      in the sand cricket Gryllus firmus using a diallel cross of inbred lines. Sex
      linkage was shown to be nonsignificant for development time but the other traits
      could not be tested. We assume that they are nonsignificant but use the term
      'reciprocal' effects to include this effect. We show that reciprocal effects are
      present in the growth traits and development time, where they account for 10-30%
      of the phenotypic variance. They are not present in adult size as indexed by head
      width. We demonstrate that reciprocal effects are due, at least in part, to
      maternal effects by an analysis of the positive correlation between egg size, a
      maternal trait, and the growth traits. The growth rate traits show no significant
      decline with age either with respect to extra-nuclear contributions to variance
      or difference between phenotypic means of reciprocal pairs. This study
      demonstrates that extra-nuclear effects are important contributors to the
      phenotypic variation in life history traits of G. firmus.

PMID- 15149409
TI  - Predation and the persistence of melanic male mosquitofish (Gambusia holbrooki).
AB  - The empirical reasons for the persistent rarity of a genotype are typically
      complex and tedious to identify, particularly in nature. Yet rare morphs occur in
      a substantial fraction of phenotypic polymorphisms. A colour polymorphism has
      persisted for decades in the eastern mosquitofish, yet why this is so remains
      obscure. Here, I report the results of (1) intensive sampling at 45 natural sites
      to obtain the frequency distribution of the melanic (black) mosquitofish morph in
      Florida, (2) predation trials, conducted independently in mesocosms, with three
      different predatory species and (3) two mark-recapture studies, conducted in
      nature. This work (1) documents the rarity of melanic mosquitofish in nature, (2)
      demonstrates that melanic males experience a selective advantage over silver
      males in the presence of predators, (3) indicates no difference in the colour
      morphs' survival at a natural site essentially devoid of these predators,
      although suggesting a higher rate of recapture for melanic males at a site rife
      with predators. Overall, selective predation appears to contribute to the
      persistence of the melanic morph, despite its rarity in nature.

PMID- 15149410
TI  - Mimicry and the evolution of premating isolation in Heliconius melpomene
      Linnaeus.
AB  - Ecological divergence can cause speciation if adaptive traits have pleiotropic
      effects on mate choice. In Heliconius butterflies, mimetic patterns play a role
      in mate detection between sister species, as well as signalling to predators.
      Here we show that male butterflies from four recently diverged parapatric
      populations of Heliconius melpomene are more likely to approach and court their
      own colour patterns as compared with those of other races. A few exceptions,
      where males were more attracted to patterns other than their own, suggest that
      some mimetic patterns are sub-optimal in mate choice. Genotype frequencies in
      hybrid zones between races of H. melpomene suggest that mating is random, so
      reinforcement is unlikely to have played a role in intra-specific divergence. In
      summary, co-evolved divergence of colour pattern and mate preference occurs
      rapidly and is likely the first step in Heliconius speciation.

PMID- 15149411
TI  - Wolbachia affects oviposition and mating behaviour of its spider mite host.
AB  - Wolbachia bacteria are transmitted from mother to offspring via the cytoplasm of
      the egg. When mated to males infected with Wolbachia bacteria, uninfected females
      produce unviable offspring, a phenomenon called cytoplasmic incompatibility (CI).
      Current theory predicts that 'sterilization' of uninfected females by infected
      males confers a fitness advantage to Wolbachia in infected females. When the
      infection is above a threshold frequency in a panmictic population, CI reduces
      the fitness of uninfected females below that of infected females and,
      consequently, the proportion of infected hosts increases. CI is a mechanism that
      benefits the bacteria but, apparently, not the host. The host could benefit from
      avoiding incompatible mates. Parasite load and disease resistance are known to be
      involved in mate choice. Can Wolbachia also be implicated in reproductive
      behaviour? We used the two-spotted spider mite - Wolbachia symbiosis to address
      this question. Our results suggest that uninfected females preferably mate to
      uninfected males while infected females aggregate their offspring, thereby
      promoting sib mating. Our data agrees with other results that hosts of Wolbachia
      do not necessarily behave as innocent bystanders - host mechanisms that avoid CI
      can evolve.

PMID- 15149412
TI  - Mate recognition in a freshwater fish: geographical distance, genetic
      differentiation, and variation in female preference for local over foreign males.
AB  - It often is assumed that more distant allopatry should reflect reduced rates of
      contemporary gene flow and/or greater divergence in mate recognition systems.
      This assumption, however, is rarely tested and may not always be appropriate.
      Here we investigated female preference for local and foreign males in a
      morphologically variable Australian freshwater fish, the Pacific blue-eye
      Pseudomugil signifer. Using a multidisciplinary approach that combined molecular
      phylogeography with conventional mate choice experiments, we found female blue
      eyes spent more time in association with local males only when the alternative
      was a foreigner from a geographically and genetically more distant population.
      When offered the choice between two foreign males, females associated more with
      males from the population that was more closely adjacent to their own. Our
      results suggest that female preference for local over foreign males in blue-eyes
      may depend on how genetically and geographically separated populations are from
      one another.

PMID- 15149413
TI  - Nonlinear relationships and phylogenetically independent contrasts.
AB  - The method of phylogenetically independent contrasts is commonly used for
      exploring cross-taxon relationships between traits. Here we show that this
      phylogenetic comparative method (PCM) can fail to detect correlated evolution
      when the underlying relationship between traits is nonlinear. Simulations
      indicate that statistical power can be dramatically reduced when independent
      contrasts analysis is used on nonlinear relationships. We also reanalyze a
      published data set and demonstrate that ignoring nonlinearity can affect
      biological inferences. We suggest that researchers consider the shape of the
      relationship between traits when using independent contrasts analysis.
      Alternative PCMs may be more appropriate if data cannot be transformed to meet
      assumptions of linearity.

PMID- 15149414
TI  - Evolutionary dynamics of a B chromosome invasion in island populations of the
      grasshopper Eyprepocnemis plorans.
AB  - Four natural populations of the grasshopper Eyprepocnemis plorans in the Mallorca
      island were analysed for several years revealing the recent invasion of the B1
      chromosome from the south-west part of the island (Palma region) towards the
      north and to the east. In only 10 years, the mean number of Bs in the northern
      population at Pollenca increased from 0.053 to 0.692. Therefore, B chromosome
      invasion seems to be very rapid and has recently arrived to the north of the
      island. The south-west (close to Palma) is the most likely point at which B
      invasion started in the Mallorca Island. Finally, the number of B chromosomes was
      significantly associated to an increase in chiasma frequency (and thus
      recombination) in A chromosomes.

PMID- 15149417
TI  - Reversal of remodeling in atrial fibrillation: a positive double-negative?

PMID- 15149418
TI  - Acute effects of left atrial radiofrequency ablation on atrial fibrillation.
AB  - INTRODUCTION: Acutely, when left atrial ablation is performed during atrial
      fibrillation (AF), the AF may persist and require cardioversion, or it may
      convert to sinus rhythm or to atrial tachycardia/flutter. The prevalence of these
      acute outcomes has not been described. METHODS AND RESULTS: Left atrial ablation,
      usually including encirclement of the pulmonary veins, was performed during AF in
      144 patients with drug-refractory AF. Conversion to sinus rhythm occurred in 19
      patients (13%), to left atrial tachycardia in 6 (4%), and to atrial flutter in 6
      (4%). In the 6 patients with a focal atrial tachycardia, the mean cycle length
      was 294 +/- 45 ms. The tachycardia arose in the left atrial roof in 3 patients,
      the left atrial appendage in 2, and the anterior left atrium in 1. In 3 of 6
      patients, the focal atrial tachycardia originated in an area that displayed a
      relatively short cycle length during AF. In 6 patients, AF converted to
      macroreentrant atrial flutter with a mean cycle length of 253 +/- 47 ms,
      involving the mitral isthmus in 5 patients and the septum in 1 patient. All
      atrial tachycardias and flutters were successfully ablated with 1 to 15
      applications of radiofrequency energy. CONCLUSION: When left atrial ablation is
      performed during AF, the AF may convert to atrial tachycardia or flutter in
      approximately 10% of patients. Focal atrial tachycardias that occur during
      ablation of AF may be attributable to driving mechanisms that persist after AF
      has been eliminated, whereas atrial flutter results from incomplete ablation
      lines.

PMID- 15149419
TI  - Learning while burning: further evidence for drivers and fibrillatory conduction
      as a mechanism for atrial fibrillation.

PMID- 15149416
TI  - Reversal of electrical remodeling after cardioversion of persistent atrial
      fibrillation.
AB  - INTRODUCTION: In animals, atrial fibrillation results in reversible atrial
      electrical remodeling manifested as shortening of the atrial effective refractory
      period, slowing of intra-atrial conduction, and prolongation of sinus node
      recovery time. There is limited information on changes in these parameters after
      cardioversion in patients with persistent atrial fibrillation. METHODS AND
      RESULTS: Thirty-eight patients who had been in atrial fibrillation for 1 to 12
      months underwent electrophysiologic testing 10 minutes and 1 hour after
      cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat
      testing. Reverse remodeling of the effective refractory period was not uniform
      across the three atrial sites tested. At the lateral right atrium, there was a
      highly significant increase in the effective refractory period between 10 minutes
      and 1 hour after cardioversion (drive cycle length 400 ms: 204 +/- 17 ms vs 211
      +/- 20 ms, drive cycle length 550 ms: 213 +/- 18 ms vs 219 +/- 23 ms, P < 0.001).
      The effective refractory period at the coronary sinus and distal coronary sinus
      did not change in the first hour but had increased by 1 week. The corrected sinus
      node recovery time did not change in the first hour but was shorter at 1 week
      (606 +/- 311 ms vs 408 +/- 160 ms, P = 0.009). P wave duration also was shorter
      at 1 week (135 +/- 18 ms vs 129 +/- 13 ms, P = 0.04) consistent with increasing
      atrial conduction velocity. CONCLUSION: The atrial effective refractory period
      increases, sinus node function improves, and atrial conduction velocity goes up
      in the first week after cardioversion of long-standing atrial fibrillation in
      humans. Reverse electrical remodeling of the effective refractory period occurs
      at different rates in different regions of the atrium.

PMID- 15149420
TI  - Atrial activation mapping in sinus rhythm in the clinical electrophysiology
      laboratory: observations during Bachmann's bundle block.
AB  - INTRODUCTION: The high posterolateral right atrium (RA) is considered the "sinus
      node area," but we lack information on endocardial atrial activation in sinus
      rhythm. We studied RA and left atrial (LA) endocardial activation in the
      electrophysiology laboratory. METHODS AND RESULTS: Thirty-five patients (21 men)
      aged 47 +/- 16.4 years (mean +/- SD) underwent RA mapping (22.2 +/- 3.8 points).
      In 21 patients, LA activation was mapped (11.1 +/- 3.9 points) through the
      coronary sinus (CS), right pulmonary artery, and/or a patent oval foramen.
      Fourteen patients had atrial arrhythmias, and 3 an ECG pattern of Bachmann's
      bundle block. Endocardial RA activation preceded P wave in 5 (-14 +/- 4.2 ms),
      coincided in 11, and followed P onset in 18 (16.7 +/- 6.6 ms). Location of the
      zero point varied from the superior vena cava to the low RA and from lateral to
      paraseptal RA. In 19 patients, activation started simultaneously in 2 to 5 points
      located >or=1 cm apart. RA activation was descending in most, but in 3 with low
      onset there was collision in the anterior and septal walls. In 15 of 21 patients,
      descending LA activation dominated, ending in the mid CS in 12, proximal CS in 1,
      and simultaneously throughout the CS in 2. In 3 with Bachmann's bundle block, CS
      activation was ascending and in 2 double potentials were recorded from the LA
      roof. CONCLUSION: During stable sinus rhythm, RA activation can start in
      different areas or simultaneously over large areas resulting in different
      activation patterns, both in the RA and the LA. LA activation is predominantly
      descending, but in Bachmann's bundle block it becomes ascending, and double
      potentials suggest a location of block in the LA roof.

PMID- 15149421
TI  - Efficacy and safety of segmental ostial versus circumferential extra-ostial
      pulmonary vein isolation for atrial fibrillation.
AB  - INTRODUCTION: Pulmonary vein (PV) isolation for atrial fibrillation (AF) can be
      performed using a segmental ostial or a circumferential extra-ostial approach.
      The relative merits and potential limitations of each approach are currently
      debated. Here we report our early experience with each of these approaches,
      including their relative efficacy and safety. METHODS AND RESULTS: Forty patients
      with drug-refractory AF underwent segmental ostial PV isolation and were compared
      to 40 consecutive patients who underwent PV isolation using a circumferential
      extra-ostial approach. The latter approach described here is novel in two
      aspects: (1) the endpoint for ablation was PV isolation and not only delay in
      left atrial to PV conduction time, and (2) isolation of the right and left PVs
      was achieved by a single encirclement of ipsilateral veins. At follow-up, 60% of
      the patients in the segmental group were free of AF compared to 75% of the
      patients in the circumferential group. There was one thromboembolic
      cerebrovascular complication during the ablation procedure in each group.
      CONCLUSION: PV isolation using a circumferential extra-ostial approach, where the
      ipsilateral PVs are isolated together by one encircling line of block using
      electroanatomic mapping, is a technically feasible procedure. This approach is at
      least as effective and safe as the more established segmental ostial approach for
      AF ablation.

PMID- 15149422
TI  - Characterization of a new pulmonary vein variant using magnetic resonance
      angiography: incidence, imaging, and interventional implications of the "right
      top pulmonary vein".
AB  - INTRODUCTION: Catheter ablation of the pulmonary veins (PVs) for prevention of
      recurrent atrial fibrillation requires precise anatomic information. We describe
      the characteristics of a new anatomic variant of PV anatomy using magnetic
      resonance angiography. METHODS AND RESULTS: A 1.5-T magnetic resonance imaging
      system with a body coil or a torso phased-array coil was used before and after
      gadolinium injection. Magnetic resonance angiograms were acquired with a breath
      hold three-dimensional fast spoiled gradient-echo imaging sequence in the coronal
      plane. Three-dimensional reconstruction with maximum intensity projections and
      multiplanar reformations was performed. A newly described variant PV ascending
      from the roof of the left atrium was found in 3 of 91 subjects. The mean ostial
      diameter of the roof PV was 7 +/- 2 mm, the mean distance from the ostium to the
      first branching point was 22 +/- 8.5 mm, and the mean distance to the right
      superior PV was 3.3 +/- 0.6 mm. CONCLUSION: We refer to the newly described
      variant of PV anatomy as the "right top pulmonary vein." It is important to be
      aware of this anatomic pattern to avoid inadvertent catheter intubation, which
      can result in misleading mapping results and PV stenosis.

PMID- 15149423
TI  - Relationship between QRS duration and left ventricular dyssynchrony in patients
      with end-stage heart failure.
AB  - INTRODUCTION: Patients with end-stage heart failure and a wide QRS complex are
      considered candidates for cardiac resynchronization therapy (CRT). However, 20%
      to 30% of patients do not respond to CRT. Lack of left ventricular dyssynchrony
      may explain the nonresponse. Accordingly, we evaluated the presence of left
      ventricular dyssynchrony using tissue Doppler imaging (TDI) in 90 consecutive
      patients with heart failure. METHODS AND RESULTS: Ninety patients with severe
      heart failure (left ventricular ejection fraction <35%, New York Heart
      Association class III-IV) were prospectively evaluated. Based on QRS duration, 30
      consecutive patients with a narrow QRS complex were included (QRS duration
      <or=120 ms), 30 patients with an intermediate QRS duration (120-150 ms), and 30
      patients with a wide QRS complex (>150 ms). All patients underwent TDI to assess
      left ventricular dyssynchrony. Extensive left ventricular dyssynchrony was
      defined as an electromechanical delay on TDI between the septum and lateral wall,
      the so-called septal-to-lateral delay, of >60 ms. Severe dyssynchrony was
      observed in 27% of patients with narrow QRS complex, 60% with intermediate QRS
      duration, and 70% with wide QRS complex. No relation existed between QRS duration
      and septal-to-lateral delay. CONCLUSION: From 30% to 40% of heart failure
      patients with QRS duration >120 ms do not exhibit left ventricular dyssynchrony,
      which may explain the nonresponse to CRT. Alternatively, 27% of patients with
      heart failure and a narrow QRS complex show significant left ventricular
      dyssynchrony and may be candidates for CRT.

PMID- 15149424
TI  - Heart rate dependence of the QT interval duration: differences among congenital
      long QT syndrome subtypes.
AB  - INTRODUCTION: The heart rate dependence of QT interval duration is abnormal in
      patients with congenital long QT syndrome. Patients with LQT1 have a defective
      I(Ks) current, a major determinant of QT response to heart rate. METHODS AND
      RESULTS: We studied the heart rate dependence of QT interval duration in
      different long QT syndrome genotypes and control subjects using computerized QT
      measurements obtained from Holter recordings. The dependence of QT duration on
      heart rate is steeper in long QT syndrome than in control subjects (0.347 +/-
      0.263 vs 0.162 +/- 0.083 at heart rate 100 beats/min; P < 0.05). In addition, QT
      interval is significantly longer in LQT2 and LQT3 than in LQT1 patients at slow
      (533 +/- 23 ms vs 468 +/- 30 ms at heart rate 60 beats/min; P < 0.0001) but not
      at rapid heart rate. The heart rate dependence of QT interval is steeper in LQT2
      and LQT3 than in LQT1 (0.623 +/- 0.245 vs 0.19 +/- 0.079 at heart rate 100
      beats/min; P < 0.05). For a given heart rate, the QT intervals vary more in LQT2
      and LQT3 than in LQT1 patients (25.98 +/- 11.18 ms vs 14.39 +/- 1.55 ms; P <
      0.01). CONCLUSION: Individual long QT syndrome genotypes differ with respect to
      QT interval dependence on heart rate. These differences may relate to the
      propensity of LQT2 and LQT3 patients to develop arrhythmias during bradycardia.

PMID- 15149425
TI  - Assessment of ventricular repolarization abnormalities in congenital long QT
      syndrome.

PMID- 15149426
TI  - Common left pulmonary vein: a consistent source of arrhythmogenic atrial ectopy.
AB  - INTRODUCTION: The discovery of a consistent relationship between atrial anatomy
      and electrophysiology would have practical value and may provide insight into
      arrhythmia mechanism. We previously observed that anatomically common left
      pulmonary veins were a disproportionate source of atrial ectopy that was
      associated with the initiation of atrial fibrillation ("arrhythmogenic"). This
      report details our efforts to characterize and quantify this observation. METHODS
      AND RESULTS: One hundred subjects with paroxysmal atrial fibrillation underwent
      computed tomographic scanning to characterize left atrial anatomy and invasive
      electrophysiology study to characterize events associated with the initiation of
      atrial fibrillation. Some of these subjects also underwent radiofrequency
      catheter ablation. The left pulmonary vein was common in 14 subjects and was a
      consistent source of arrhythmogenic ectopy. This relationship was significantly
      stronger than for any other individual vein or ipsilateral vein combination.
      Myocardium located within the common vein trunk was the site of origin of the
      ectopy in most subjects. This myocardium did not have unique electrophysiologic
      properties. Catheter ablation to isolate myocardium proximal to junction between
      the common vein and the left atrial body cured all patients in whom the vein was
      the sole source of arrhythmogenic ectopy. CONCLUSION: In this cohort, a common
      left pulmonary vein was a consistent source of arrhythmogenic atrial ectopy.

PMID- 15149427
TI  - T-type calcium current in electrical activity of cardiomyocytes isolated from
      rabbit pulmonary vein.
AB  - INTRODUCTION: Pulmonary veins (PVs) are known to initiate paroxysmal atrial
      fibrillation. T-type calcium current (I(Ca-T)) has a role in normal and abnormal
      automaticity of cardiomyocytes. The aim of this study was to evaluate whether
      I(Ca-T) contributes to PV electrical activity. METHODS AND RESULTS: By whole-cell
      clamp techniques in rabbit myocytes, I(Ca-T) was identified in 12 (39%) of 31 PV
      cardiomyocytes with pacemaker activity, 2 (9%) of 23 PV cardiomyocytes without
      pacemaker activity, and 2 (15%) of 13 atrial myocytes (P < 0.05). Maximum I(Ca-L)
      and I(Ca-T) densities from PV cardiomyocytes with pacemaker activity were 6.87 +/
      2.17 pA/pF and 1.38 +/- 0.69 pA/pF, respectively. Nickel (40 microM) decreased
      the spontaneous activity in 5 (36%) of 14 PV cardiomyocytes (3.1 +/- 0.6 Hz vs
      2.2 +/- 0.5 Hz, P < 0.05), reduced the amplitudes of delayed after depolarization
      from 13 +/- 1 mV to 7 +/- 1 mV (n = 4, P < 0.05) and inhibited transient inward
      currents from 1.2 +/- 0.2 pA/pF to 0.7 +/- 0.1 pA/pF (n = 11, P < 0.01).
      CONCLUSIONS: We conclude that I(Ca-T) contributes to PV pacemaker activity and
      triggered activity, which are of functional importance in PV arrhythmogenesis.

PMID- 15149428
TI  - Fractionation of electrograms and linking of activation during pharmacologic
      cardioversion of persistent atrial fibrillation in the goat.
AB  - INTRODUCTION: During atrial fibrillation (AF), there is fractionation of
      extracellular potentials due to head-to-tail interaction and slow conduction of
      fibrillation waves. We hypothesized that slowing of the rate of AF by infusion of
      a Class I drug would increase the degree of organization of AF. METHODS AND
      RESULTS: Seven goats were instrumented with 83 epicardial electrodes on the left
      atrium, left atrial appendage, Bachmann's bundle, right atrium, and right atrial
      appendage. AF was induced and maintained by an automatic atrial fibrillator.
      After AF had persisted for 4 weeks, the Class IC drug cibenzoline was infused at
      a rate of 0.1 mg/kg/min. AF cycle length (AFCL), the percentage of fractionated
      potentials, conduction velocity (CV), and direction of propagation of the
      fibrillation waves were measured during baseline, after AFCL was increased by 20,
      40, 60, and 80 ms, and shortly before cardioversion. Infusion of cibenzoline
      increased the mean of the median AFCLs from 96 +/- 6 ms to 207 +/- 43 ms (P <
      0.0001). The temporal variation in AFCL in different parts of the atria was 8% to
      20% during control and, with the exception of Bachmann's bundle, was not
      significantly reduced during cibenzoline infusion. CV decreased from 76 +/- 14 ms
      to 52 +/- 9 cm/s (P < 0.01). Cibenzoline increased the percentage of single
      potentials from 81%+/- 4% to 91%+/- 4% (P < 0.01) and decreased the incidence of
      double potentials from 14%+/- 4% to 7 +/- 5% (P < 0.01) and multiple potentials
      from 5%+/-% to 1%+/- 2% (P < 0.001). Whereas during control, linking (consecutive
      waves propagating in the same direction) during seven or more beats occurred in
      9%+/- 15% of the cycles, after cibenzoline the degree of linking had increased to
      40%+/- 33% (P < 0.05). During the last two beats before cardioversion, there was
      a sudden prolongation in AFCL from 209 +/- 37 ms to 284 +/- 92 ms (P < 0.01) and
      a strong reduction in fractionated potentials (from 22%+/- 12% to 6%+/- 5%, P <
      0.05). CONCLUSION: The Class IC drug cibenzoline causes a decrease in
      fractionation of fibrillation electrograms and an increase in the degree of
      linking during AF. This supports the observation that Class I drugs widen the
      excitable gap during AF.

PMID- 15149429
TI  - Improvement of defibrillation efficacy with preshock synchronized pacing.
AB  - INTRODUCTION: We previously demonstrated that wavefront synchronization by
      spatiotemporal excitable gap pacing (Sync P) is effective at facilitating
      spontaneous termination of ventricular fibrillation (VF). Therefore, we
      hypothesized that a spatiotemporally controlled defibrillation (STCD) strategy
      using defibrillation shocks preceded by Sync P can improve defibrillation
      efficacy. METHOD AND RESULTS: We explored the STCD effects in 13 isolated rabbit
      hearts. During VF, a low-voltage gradient (LVG) area was synchronized by Sync P
      for 0.92 second. For Sync P, optical action potentials (OAPs) adjacent to four
      pacing electrodes (10 mm apart) were monitored. When one of the electrodes was in
      the excitable gap, a 5-mA current was administered from all electrodes. A shock
      was delivered 23 ms after the excitable gap when the LVG area was unexcitable.
      The effects of STCD was compared to random shocks (C) by evaluating the
      defibrillation threshold 50% (DFT(50); n = 35 for each) and preshock coupling
      intervals (n = 208 for STCD, n = 172 for C). Results were as follows. (1) Sync P
      caused wavefront synchronization as indicated by a decreased number of phase
      singularity points (P < 0.0001) and reduced spatial dispersion of VF cycle length
      (P < 0.01). (2) STCD decreased DFT(50) by 10.3% (P < 0.05). (3) The successful
      shocks showed shorter preshock coupling intervals (CI; P < 0.05) and a higher
      proportion of unexcitable shock at the LVG area (P < 0.001) than failed shocks.
      STCD showed shorter CIs (P < 0.05) and a higher unexcitable shock rate at LVG
      area (P < 0.05) than C. CONCLUSION: STCD improves defibrillation efficacy by
      synchronizing VF activations and increasing probability of shock delivery to the
      unexcitable LVG area.

PMID- 15149430
TI  - Parasympathetic cardiac nerve stimulation with implanted coronary sinus lead.
AB  - A patient with drug-refractory paroxysmal atrial fibrillation associated with
      rapid ventricular rate underwent biatrial pacemaker implantation. During elective
      replacement of the pacemaker, a significant voltage- and frequency-dependent
      decrease in ventricular rate was achieved by high-frequency electrical
      stimulation (17 Hz) of parasympathetic cardiac nerves innervating the AV node
      with the implanted bipolar coronary sinus electrode. The negative dromotropic
      effect of parasympathetic stimulation was eliminated by intravenous
      administration of 1-mg atropine.

PMID- 15149432
TI  - Utility of implantable cardioverter defibrillator electrograms to estimate
      repolarization alternans preceding a tachyarrhythmic event.
AB  - Electrical alternans is a pattern of variation in the shape of the ECG waveform
      that appears on an every-other-beat basis. In humans, alternation in ventricular
      repolarization, namely, repolarization alternans, has been associated with
      increased vulnerability to ventricular tachycardia/ventricular fibrillation and
      sudden cardiac death. This study investigates the utility of implantable
      cardioverter defibrillator electrograms to estimate repolarization alternans
      preceding a tachyarrhythmic event. It is demonstrated that microvolt-level
      repolarization alternans is present prior to an arrhythmic event, and one can
      record low-amplitude-noise signals that can be used to obtain reliable estimates
      of repolarization alternans. This study eventually may lead to new methods that
      would prevent the onset of malignant tachyarrhythmias.

PMID- 15149431
TI  - Case of polymorphic ventricular tachycardia in diphenhydramine poisoning.
AB  - This is the first reported case of torsades de pointes attributable to
      diphenhydramine, a drug with weak I(Kr) effects. A 26-year-old, healthy man was
      admitted to intensive care after a diphenhydramine overdose. Results of physical
      examination, ECG, and electrolytes were normal at admission. Despite supportive
      care, he developed typical, sustained, torsades de pointes with a markedly
      prolonged QT interval requiring cardioversion. Drugs with weak I(Kr)-blocking
      effects may cause lethal proarrhythmia in susceptible individuals when delivered
      in high concentrations. This case illustrates the variation in repolarization
      reserve that exists in a free-standing population.

PMID- 15149434
TI  - Irregular tachycardia with varying degrees of bundle branch block aberration:
      what is the mechanism?

PMID- 15149433
TI  - Potassium channels and membrane potential in the modulation of intracellular
      calcium in vascular endothelial cells.
AB  - The endothelium plays a vital role in the control of vascular functions,
      including modulation of tone; permeability and barrier properties; platelet
      adhesion and aggregation; and secretion of paracrine factors. Critical signaling
      events in many of these functions involve an increase in intracellular free
      Ca(2+) concentration ([Ca(2+)](i)). This rise in [Ca(2+)](i) occurs via an
      interplay between several mechanisms, including release from intracellular
      stores, entry from the extracellular space through store depletion and second
      messenger-mediated processes, and the establishment of a favorable
      electrochemical gradient. The focus of this review centers on the role of
      potassium channels and membrane potential in the creation of a favorable
      electrochemical gradient for Ca(2+) entry. In addition, evidence is examined for
      the existence of various classes of potassium channels and the possible influence
      of regional variation in expression and experimental conditions.

PMID- 15149435
TI  - Electrical disconnection of the superior vena cava from the right atrium.

PMID- 15149438
TI  - ECG algorithm for idiopathic ventricular outflow tract tachycardia.

PMID- 15149436
TI  - The clinical utility and diagnostic value of the head-up tilt testing (HUT)
      protocol.

PMID- 15149440
TI  - Double potentials as a criterion for cavotricuspid isthmus block?

PMID- 15149441
TI  - Cardiac pacing: how it started, where we are, where we are going.

PMID- 15149442
TI  - A skin for the imaginal.
AB  - This paper focuses on the development of internal space, the evolution of
      psychological boundaries and the capacity for symbolization as they first arise
      during infancy. The concept of the psychic skin as an early form of psychological
      boundary is presented. The development of the psychic skin, or psychological
      container, is necessary for imaginal processes to function for the purpose of
      psychological growth and development. Infant observation material utilizing the
      Tavistock model and analytical material from an adolescent analysis is presented
      to help elucidate the theoretical concepts.

PMID- 15149444
TI  - Revisiting Jung's concept of innate sensitiveness.
AB  - Jung suggested that innate sensitiveness predisposes some individuals to be
      particularly affected by negative childhood experiences, so that later, when
      under pressure to adapt to some challenge, they retreat into infantile fantasies
      based on those experiences and become neurotic. Recent research by the author and
      others is reviewed to support Jung's theory of sensitiveness as a distinctly
      thorough conscious and unconscious reflection on experiences. Indeed, this
      probably innate tendency is found in about twenty percent of humans, and, in a
      sense, in most species, in that about this percentage will evidence a strategy of
      thoroughly processing information before taking action, while the majority depend
      on efficient, rapid motor activity. Given this thorough processing, sensitive
      individuals readily detect subtleties-including whatever is distressing or
      threatening. Hence, as Jung observed, given the same degree of stress in
      childhood as non-sensitive individuals, sensitive persons will develop more
      depression, anxiety, and shyness. Without undue stress, they evidence no more of
      these difficulties than the non-sensitive-or even less, being unusually aware of
      supportive as well as negative cues from caregivers. Given this interaction, one
      treatment task is to distinguish the effects of such childhood difficulties from
      what does not need treatment, which are the typical effects of the trait itself
      on an adult without a troubled developmental history.

PMID- 15149443
TI  - Psychic phenomena and early emotional states.
AB  - This paper examines the relationship between severe early trauma and the
      development of psychic intuition. A case presentation with extensive dream work
      helps to illustrate this connection by exploring the psychological meaning of one
      patient's acute receptivity to unconscious communications. The paper includes a
      historical overview of Freud's attitudes toward occultism, as distinct from later
      psychoanalytic views, including those of Wilfred Bion. Many of Bion's views have
      more in common with Jung's perspective than with Freud's, with particular
      reference made to spiritual and religious differences. Bion clearly states that
      Freud and psychoanalysts have focused on phenomena, not on noumena, which Bion
      considers to be the essence of the psychoanalytic point of view.

PMID- 15149445
TI  - This new science of ours: a more or less systematic history of consciousness and
      transcendence. Part II.
AB  - Part I of this paper having postulated the locus of consciousness as residing in
      a field between primitive mind in participation mystique with the world and a
      transcendent ground of being, Part II takes up the nature of mind itself in this
      field in terms of in vivo experiences. Operations and manifestations of
      consciousness are inexhaustively explored in four venues: 1) Jung's life
      experiences, 2) Joseph Henderson's theory of psychic development, 3) Eric
      Voegelin's theory of consciousness and 4) the experiences of analytic patients in
      far reaches of very long analyses.

PMID- 15149446
TI  - Re-visioning the spider woman archetype in Kiss of the Spider Woman.
AB  - The article examines the transformation of spider woman archetype from Manuel
      Puig's adaptation of his novel to a play, and other adaptations into a film and a
      musical. The paper examines how the archetype's image and function shift when 're
      visioned' by various artists and performed in disparate social contexts.

PMID- 15149447
TI  - The Hours: the 'as-if' personality and problems of loving.

PMID- 15149448
TI  - Sabina Spielrein: a bibliography.
AB  - The work on this bibliography was carried out mostly in 2002. Though it aims at
      being exhaustive, the research in different languages and translations may not
      have yielded every document and some may still be unknown to me. It is also
      likely that more material have been translated since. Besides, the Spanish and
      Brazilian-Portuguese literature has not been researched. This is why this
      bibliography must be considered as a 'work in progress' which any addition can
      only enrich. Victor Ovcharenko has made a list of the writings of Sabina
      Spielrein starting with 1911, the year of her medical thesis in Zurich, and
      covering the years to 1931. He points out, however, that between the date of the
      last paper that she is known to have written and her death in 1942, there are
      eleven years and that it would be truly astonishing if she had neither written
      nor published anything during that period. Up to this date no document by her
      during that time has been found (Journal of Analytical Psychology, 44, 3, 1999).

PMID- 15149449
TI  - An interview with Elisabeth Marton [interviewed by Covington Coline].

PMID- 15149450
TI  - Comments on the film My Name was Sabina Spielrein.

PMID- 15149451
TI  - Comments on "Picture interpretation and Jungian typology" (Journal of Analytical
      Psychology, Feb. 2003, 48, I, 83-99) by D. P. Bergeron, D. H. Rosen, R. C. Arnau
      & N. Mascaro.

PMID- 15149457
TI  - Opportunities for an improved role for nurses in psychoactive substance use:
      review of the literature.
AB  - Nurses form a core component of many health care systems so their role in
      responding to problems related to psychoactive substance use is crucial. They are
      often under-utilized, mainly because of anxieties concerning role adequacy,
      legitimacy, lack of support and failure to implement interventions in a variety
      of settings. Nurses have unique opportunities through interactions they have with
      young people, families and significant others. Training and career preparation
      should encompass development of innovative strategies, taking a leading role in
      management of substance use patients, involvement in the treatment of the
      homeless mentally ill, HIV-infected individuals and persons with dual disorders
      of mental health and substance use. Future directions should focus on developing
      skills for critical thinking, preventive and therapeutic interventions, clinical
      judgement, effective organizational capacity and team work. Barriers such as
      scope of practice, authority, ethical and legal issues surrounding health care
      for substance use need to be addressed.

PMID- 15149456
TI  - Oral health and older people.

PMID- 15149458
TI  - Study abroad as a process of learning intercultural competence in nursing.
AB  - The aim of this research was to describe an international student exchange
      programme as a context of learning intercultural competence in nursing. Twelve
      Finnish nursing students who had participated in an exchange programme in the
      United Kingdom participated. The data consisted of group interviews, learning
      documents, background questionnaires and research diary notes, and the method of
      inductive content analysis was used. Study abroad as a process of learning
      intercultural competence consisted of three ethno-categories: transition from one
      culture to another, adjustment to the difference and gaining intercultural
      sensitivity. The exchange programme as a context of learning intercultural
      competence was characterized by a problematic orientation phase, a study abroad
      phase that involved stressful but rewarding adjustment to the intercultural
      differences and an inadequate re-entry debriefing phase. In order for the
      international experience of nursing students to have an impact on their
      understanding of diversity, they need assistance in each phase of the programme.
      Particularly, the students need intercultural tutoring and mentoring to venture
      into encounters with local people, including direct client contacts, during their
      study abroad.

PMID- 15149459
TI  - Managing as carers of stroke survivors: strategies from the field.
AB  - Family members are required to provide increasingly complex care to relatives in
      the home. Stroke is a major cause of disability and there is increasing pressure
      being placed on carers to provide on-going support to stroke survivors living in
      the community. This study involved interviewing carers to determine their
      perspectives on the support and educational needs they require and the coping
      strategies they used. Data analysis revealed that carers experienced considerable
      uncertainty about their role as carers and their future and that they used a
      number of coping strategies to manage in their caring role. The coping strategies
      adopted by the carers included remaining positive, adapting to change, comparing
      their situation with others who were worse off, changing their employment status,
      humour, switching off and using family support. It is important for health care
      professionals to understand the complex role of the carers and to advise them on
      strategies they can use to assist managing this role.

PMID- 15149460
TI  - Reasons for attending and not attending a support group for recipients of
      implantable cardioverter defibrillators and their carers.
AB  - There is evidence to suggest that people who have an implantable cardioverter
      defibrillator and their caregivers experience psychological distress. This
      qualitative descriptive study explored the experiences, concerns and needs of
      recipients of implantable cardioverter defibrillators and their caregivers who
      attended or did not attend a support group organized by a public hospital located
      in Perth, Western Australia, Australia. Eleven recipients of implantable
      cardioverter defibrillators and their caregivers participated in this study.
      Among those who attended the support group, four major themes were identified:
      providing information, connecting with others, helping others and attendance.
      Explanations for non-attendance included difficulties attending because of the
      location, not wanting to be reminded about the implantable cardioverter
      defibrillator, and a perception, among younger recipients, that the support group
      was comprised of mainly older recipients with whom they had little in common.

PMID- 15149461
TI  - Is there evidence of the International Classification of Functioning, Disability
      and Health in undergraduate nursing students' patient assessments?
AB  - This paper reports on a secondary analysis of undergraduate nursing students'
      patient assessments while on clinical placement in a rehabilitation setting in
      search of evidence of the International Classification of Functioning, Disability
      and Health (ICF). It describes the evolution of the original World Health
      Organization's International Classification of Impairment, Disability and
      Handicap into the ICF. Data was analysed using the ICF categories of function,
      activity, participation, environmental factors and personal factors. Some
      evidence of ICF was revealed. Nurses are encouraged to further explore the
      relevance of ICF for nursing.

PMID- 15149462
TI  - Prediction of pregnancy by intrauterine insemination using CASA estimates and
      strict criteria in patients with male factor infertility.
AB  - This study was performed to predict pregnancy by intrauterine insemination (IUI)
      using computer-aided sperm analysis (CASA) estimates and strict criteria in
      patients with male factor infertility. IUI was performed in 682 cycles on 160
      male factor infertile patients. Semen examinations were carried out by CASA and
      strict criteria before and after sperm preparation using continuous-step density
      gradient centrifugation. Receiver operating characteristics (ROC) curves were
      constructed for assessment of the effectiveness of each individual parameter in
      predicting pregnancy by IUI. A clinically acceptable threshold was calculated
      when sensitivity plus specificity were maximum. The average cycle of IUI
      performed was 4.3 +/- 2.4. Pregnancy rate per cycle and per patient were 7.2%
      (49/682) and 28.1% (45/160), respectively. Using ROC curve, it was shown that
      normal sperm morphology assessed by the strict criteria before sperm separation
      and five parameters after sperm separation including rapid, progressive motility,
      average path velocity (VAP), curvilinear velocity (VCL), and straight line
      velocity (VSL) were able to predict pregnancy by IUI. Correlation between sperm
      parameters and pregnancy outcome was examined by the logistic regression model.
      In a multivariate analysis normal morphology before sperm separation >or=15.5%
      [odds ratio (OR) = 2.2, p = 0.02], rapid after sperm separation >or=25.5% [OR =
      3.9, p = 0.029], and VCL after sperm separation >or=102.65 microm/sec [OR = 3.2,
      p = 0.002] were the parameters of predictive value for pregnancy outcome.
      Adjustment of the model for female age, female infertility factors, and the
      methods of ovulation induction did not change this finding, and the final model
      still had the same covariates. Pregnancy rates per cycle according to the number
      (0, 1, 2 and 3) of variables satisfied with the three parameters were 0% (0/110),
      1.6% (3/183), 9.7% (21/217) and 15.1% (23/151), respectively. Three semen
      parameters including normal morphology before sperm separation, rapid and VCL
      after sperm separation were identified as predictors of pregnancy by IUI. These
      variables would be helpful when counselling patients before they make the
      decision to proceed with in vitro fertilization (IVF)/intracytoplasmic sperm
      injection (ICSI)-ET.

PMID- 15149463
TI  - Interaction between leucocytes and human spermatozoa influencing reactive oxygen
      intermediates release.
AB  - The relationship between the presence of white blood cells (WBCs) and the
      fertilizing potential of human semen is still an open question. It is well known
      that the presence of leucocytes in human semen can be related to the production
      of reactive oxygen intermediates (ROI). Semen samples were obtained from 15
      normozoospermic men and leucocytes were isolated from heparinized blood drawn
      from 15 volunteers. Lucigenin and luminol-mediated chemiluminescence assays were
      used to determine reactive oxygen species (ROS) generation by non-activated or
      activated leucocytes through 12-myristate-13-acetate or N-formyl-methionyl-leucyl
      phenyalanine (FMLP) before the addition of spermatozoa isolated by swim-up or
      Percoll procedures. All spermatozoal fractions used in this study were
      characterized by defining their motility, morphology and viability. The levels of
      ROS formation by non-activated as well as stimulated leucocytes were
      significantly decreased after addition of swim-up separated spermatozoa (p <
      0.01). The ability to inhibit the basal chemiluminescence was of lower degree for
      spermatozoa isolated from 90% Percoll fractions than for swim-up sperm. However,
      addition of sperm cells from 47% Percoll fraction was found to increase both
      lucigenin and luminol signals. Moreover, the determined ROI levels changed
      depending on the type of inducing factor used for oxidative burst. Then,
      spermatozoa selected by swim-up procedure although with only slightly higher
      viability and morphology than sperm obtained from 90% Percoll fraction clearly
      exhibited much higher capacity to inhibit ROI secretion by receptor-stimulated
      leucocytes (FMLP-activation) than Percoll fractionated sperm. Such results may
      indicate that within normal semen may exist sperm subpopulations with different
      biochemical mechanisms controlling the interaction between spermatozoa and
      contaminating leucocytes. When ROI levels contained in normozoospermic semen are
      dependent on the WBCs activation, it seems that spermatozoa with preserved normal
      functional competence are able to defend themselves against leucocytes-derived
      ROI. Also for normozoospermic ejaculates, swim-up sperm may improve semen
      antioxidant characteristics when comparing with Percoll (90%) separated sperm. It
      may help for optimal sperm preparation when assisting to infertility treatment.

PMID- 15149464
TI  - Clinical analysis of patients with azoospermia factor deletions by
      microdissection testicular sperm extraction.
AB  - Microdeletions of the azoospermia factor (AZF) locus on the Y chromosome have
      been implicated as a major genetic component of idiopathic male infertility, and
      the incidence of AZF deletions has been reported to be 15-20% in men with non
      obstructive azoospermia (NOA). Numerous studies have described AZF deletion rates
      in patients with azoospermia; however, a clinical comparison of azoospermic
      patients with AZF deletion and those with no deletion has not been reported well.
      A new technique for testicular sperm extraction, microdissection testicular sperm
      extraction (TESE), has been used widely on NOA patients. Although testicular
      spermatozoa are reliably detected and retrieved from NOA patients by
      microdissection TESE, sperm retrieval rates for patients with AZF deletions are
      not well known. Therefore, characteristics of NOA patients with AZF deletion were
      investigated. Six of 60 patients (10%) who underwent microdissection TESE were
      found to have AZF deletions by genomic polymerase chain reaction. Testicular
      data, outcome of sperm retrieval and endocrinological profiles, were compared
      between patients with AZF deletions (n = 6) and those with no deletions (n = 54).
      Testicular size, varicocele rates and testicular histology were similar between
      the groups. Significant differences were not detected in the endocrinological
      profiles. Sperm retrieval rates were not significantly different between the
      groups. In conclusion, AZF deletions do not appear to confer specific
      characteristics to NOA patients.

PMID- 15149465
TI  - Use of hydrogen peroxide to assess the sperm susceptibility to oxidative stress
      in subjects presenting a normal semen profile.
AB  - Human sperm susceptibility to oxidative stress is vital as it affects various
      characteristics of sperm function. In the present study, we report a simple,
      sensitive and quick method of assessing the capacity of the sperms to withstand
      increased oxidative stress. The basis for the test was derived from the fact that
      human sperms suspended in Ham's F-10 medium tend to lose the forward progressive
      motility when co-incubated with H(2)O(2) (600 microm). Replacement of the medium
      with seminal plasma (1: 1) was able to reduce the loss of sperm motility (40%).
      Retention of sperm motility in semen (0-30%) following 10 min of H(2)O(2) (600
      microm) exposure was taken as the criteria for delineating the quality of sperm
      as poor, moderate, good and excellent types. The protocol was tested in 87
      subjects presenting a normal semen profile. On the basis of this test, 44% of the
      semen samples were classified as poor and the rest as moderate, good or
      excellent. Lipid peroxidation was found higher in the sperms from the 'poor'
      category. Activities of superoxide dismutase and catalase were also significantly
      elevated in the seminal plasma of these subjects as compared with combined
      categories of good or excellent. The test described here can be used routinely in
      laboratory investigations to assess sperm susceptibility to oxidative stress in
      subjects presenting a normal semen profile.

PMID- 15149467
TI  - Visco-elasticity of seminal fluid in relation to the epididymal and accessory sex
      gland function and its impact on sperm motility.
AB  - Seminal viscopathy was shown to be associated with male infertility. However, our
      knowledge about the regulatory mechanism of this process is still limited. In
      semen samples from 411 men attending for fertility assessment, traditional semen
      parameters including visco-elasticity were assessed according to the World Health
      Organization guidelines. Sperm motility was evaluated by use of computer aided
      sperm analysis (CASA). Seminal activity of neutral alpha-glucosidase (NAG) and
      concentrations of prostate-specific antigen (PSA), zinc, and fructose were
      measured. The activity of NAG, and the concentrations of PSA and zinc were
      significantly lower in hyper-visco-elastic semen samples (medians: 5 vs. 8 mU/mL;
      741 vs. 924 mg/L; 1 vs. 2 mM/L), than in those with normal visco-elasticity (p =
      0.004, 0.005 and 0.011, respectively). When comparing the total amounts, only for
      seminal fructose there was a difference between samples with high visco
      elasticity as compared with those of normal visco-elasticity (median: 74 vs. 53
      microM/ejaculate, p = 0.007) This seminal marker was the only significant
      independent parameter in predicting seminal visco-elasticity in a multiple
      logistic regression analysis (odds ratio for the highest quartile = 4.67). Hyper
      visco-elasticity was associated with a lower percentage of motile spermatozoa (43
      vs. 50%, p = 0.045). Similar trend was found for the CASA motility
      characteristics curvilinear velocity (VCL), average path length (VAP), amplitude
      of lateral head displacement (ALH) (p = 0.008, 0.038 and 0.020, respectively).
      Our study demonstrated the interplay between the regulatory effect of post
      testicular organs on semen visco-elasticity. Hyper-visco-elasticity was
      associated with asthenozoospermia and lower levels of VCL, VAP and ALH.

PMID- 15149466
TI  - Native specific activity of glutathione peroxidase (GPx-1), phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does
      not differ between normo- and hypomotile human sperm samples.
AB  - Glutathione-dependent selenoenzymes in human spermatozoa are responsible for a
      generalized protection against reactive oxygen species (ROS) as well as some
      other metabolic and structural regulation during spermiogenesis and sperm cell
      maturation. Glutathione peroxidase (GPx-1), phospholipid hydroperoxide
      glutathione peroxidase (GPx-4 or PHGPx) and glutathione reductase (GR) native
      specific activities have been studied in human Percoll-purified spermatozoa from
      healthy fertile subjects and asthenozoospermic patients. The mean values obtained
      for the three enzymes in normal specimens are 1.52 +/- 0.90 mU/10(6) sperm cells
      (PHGPx), 4.26 +/- 1.73 mU/10(6) sperm cells (GPx-1) and 1.95 mU/10(6) sperm cells
      (GR). No statistically significant differences for any of the three enzymes were
      encountered between these values and those of asthenozoospermic patients. These
      results are discussed and compared with recent literature data on both rescued
      and native PHGPx specific activity in human spermatozoa, as well as with data
      obtained for GPx in human seminal plasma.

PMID- 15149468
TI  - Idiopathic non-obstructive azoospermia or severe oligozoospermia: a cross
      sectional study in 61 Greek men.
AB  - Idiopathic non-obstructive azoospermia or severe oligozoospermia (INOA) consists
      a special group of men characterized by eugonadism, primary infertility, low
      testicular volume, azoospermia or severe oligozoospermia and high follicle
      stimulating hormone values. Aims of this study were to describe the clinical,
      hormonal, sperm and histological characteristics of men with INOA and to define
      if and to what extend men with the INOA phenotype carry Y chromosome long arm
      (Yq) microdeletions. Sixty-three men with INOA were studied through clinical
      examination, spermiograms, hormonal profile, polymerase chain reaction for Yq
      microdeletions, karyotype and testicular fine-needle aspiration biopsy. Sixty
      seven men with infertility of known causes and sixty fertile men served as
      controls. Men with INOA had significantly lower total testosterone levels than
      fertile men as well as higher prevalence of loss of libido, higher luteinizing
      hormone levels and lower sperm volume whereas men with infertility of known
      causes had intermediate values. The prevalence of Yq microdeletions was 3% in men
      with INOA, 3% in men with infertility of known causes (all of them with abnormal
      karyotype) and 0% in fertile men. In conclusion, men with INOA have more severe
      testiculopathy than these with infertility of known causes. These men may be at
      increased risk of developing partial androgen deficiency of the aging male.

PMID- 15149469
TI  - Annexin V binding to plasma membrane predicts the quality of human cryopreserved
      spermatozoa.
AB  - Cryopreservation-induced stress may result in membrane injury with consequent
      decrease of sperm motility and fertilizing capacity. This study has investigated
      the relationship between human spermatozoa tolerance to cryopreservation and the
      loss of plasma membrane asymmetry, especially translocation of phosphatidylserine
      (PS) from the inner to the outer leaflet. The prospective study was performed on
      semen samples from 31 men. Conventional characteristics of 20 semen were
      analysed, before and after cryopreservation as well as externalization of PS
      assessed by annexin V-staining in combination with the propidium iodide which
      stains dead cells. The fertilizing capacity was evaluated by a zona free hamster
      egg penetration test in 11 freeze/thaw spermatozoa samples. The percentages of
      vital annexin V-negative and annexin V-positive spermatozoa in post-thaw samples
      were significantly lower than in pre-freeze ones (10 +/- 3 vs. 25 +/- 5% and 22
      +/- 3 vs. 34 +/- 4% respectively), while the percentages of dead spermatozoa
      annexin V-negative and annexin V-positive had increased (42 +/- 4 vs. 23 +/- 4%
      and 23 +/- 4 vs. 16 +/- 2% respectively). The percentages of progressive and
      total motile spermatozoa were significantly correlated with the percentage of
      vital annexin V-negative spermatozoa before as well as after cryopreservation.
      Furthermore, recovery of motile spermatozoa after freeze/thaw was strongly
      correlated (p < 0.002) with the proportion of vital annexin V-negative
      spermatozoa in fresh semen. The percentage of penetration of zona-free hamster
      eggs was correlated (p < 0.02) with the percentage of live annexin V-negative
      cryopreserved spermatozoa capacitated for 3 h. These findings provide evidence
      that annexinV-binding staining in combination with PI brings additional
      information to predict the outcome of cryopreserved ejaculated sperm and may be
      used as a novel and reliable marker to study the freeze/thaw process.

PMID- 15149472
TI  - Health policy roundtable panel discussion: translating health insurance studies
      into policy proposals.

PMID- 15149470
TI  - Effect of neonatal exposure to diethylstilbestrol on testicular gene expression
      in adult mouse: comprehensive analysis with cDNA subtraction method.
AB  - Summary In utero or neonatal exposure to high levels of exogenous steroid
      hormones, such as the potent synthetic diethylstilbestrol (DES), incurs an
      increased risk of malfunctional male reproduction. In this study, we investigated
      whether neonatal exposure to DES induces the alteration of mRNA expression in
      adult mouse testis. Using a cDNA subtraction method, we isolated seven gene
      clones whose expression was changed in neonatally DES-treated mouse testis.
      Northern blot analysis revealed that five up-regulated genes (AF326230, AF356521,
      AK004975, AK006136 and BM237156) and two down-regulated genes (AK017044,
      AK017130) were predominantly expressed in testes of 8-week-old mice. Moreover, we
      confirmed that the expression of these seven genes was altered by neonatal DES
      exposure using Northern blot analysis. Our results suggest that neonatal exposure
      to DES leads to the alteration of gene expression in the testis in the long term.
      These genes might be useful as biological markers of foetal or neonatal exposure
      to exogenous steroid hormones, such as DES.

PMID- 15149473
TI  - Working Conditions of the Nursing Workforce excerpts from a policy roundtable at
      AcademyHealth's 2003 Annual Research Meeting.

PMID- 15149474
TI  - Effects of Medicare payment changes on nursing home staffing and deficiencies.
AB  - OBJECTIVE: To investigate the effects of Medicare's Prospective Payment System
      (PPS) for skilled nursing facilities (SNFs) and associated rate changes on
      quality of care as represented by staffing ratios and regulatory deficiencies.
      DATA SOURCES: Online Survey, Certification and Reporting (OSCAR) data from 1996
      2000 were linked with Area Resource File (ARF) and Medicare Cost Report data to
      form a panel dataset. STUDY DESIGN: A difference-in-differences model was used to
      assess effects of the PPS and the BBRA (Balanced Budget Refinement Act) on
      staffing and deficiencies, a design that allows the separation of the effects of
      the policies from general trends. Ordinary least squares and negative binomial
      models were used. DATA COLLECTION METHODS: The OSCAR and Medicare Cost Report
      data are self-reported by nursing facilities; ARF data are publicly available.
      Data were linked by provider ID and county. PRINCIPAL FINDINGS: We find that
      professional staffing decreased and regulatory deficiencies increased with PPS,
      and that both effects were mitigated with the BBRA rate increases. The effects
      appear to increase with the percent of Medicare residents in the facility except,
      in some cases, at the highest percentage of Medicare. The findings on staffing
      are statistically significant. The effects on deficiencies, though exhibiting
      consistent signs and magnitudes with the staffing results, are largely
      insignificant. CONCLUSIONS: Medicare's PPS system and associated rate cuts for
      SNFs have had a negative effect on staffing and regulatory compliance. Further
      research is necessary to determine whether these changes are associated with
      worse outcomes. Findings from this investigation could help guide policy
      modifications that support the provision of quality nursing home care.

PMID- 15149475
TI  - Managed care and preventable hospitalization among Medicaid adults.
AB  - OBJECTIVE: The study examines the association between managed care enrollment and
      preventable hospitalization patterns of adult Medicaid enrollees hospitalized in
      four states. DATA SOURCES/STUDY SETTING: Hospital discharge data from the
      Healthcare Cost and Utilization Project (HCUP) database of the Agency for
      Healthcare Research and Quality (AHRQ) for New York (NY), Pennsylvania (PA),
      Wisconsin (WI), and Tennessee (TN) residents in the age group 20-64 hospitalized
      in those states, linked to the Area Resource File (ARF) and American Hospital
      Association (AHA) survey files for 1997. STUDY DESIGN: The study uses separate
      logistic models for each state comparing preventable admissions with marker
      admissions (urgent, insensitive to primary care). The model controls for
      socioeconomic and demographic variables, and severity of illness. PRINCIPAL
      FINDINGS: Consistently in different states, private health maintenance
      organization (HMO) enrollment was associated with fewer preventable admissions
      than marker admissions, compared to private fee-for-service (FFS). However,
      Medicaid managed care enrollment was not associated with a reduction in
      preventable admissions, compared to Medicaid FFS. CONCLUSIONS: Our analysis
      suggests that the preventable hospitalization pattern for private HMO enrollees
      differs significantly from that for commercial FFS enrollees. However, little
      difference is found between Medicaid HMO enrollees and Medicaid FFS patients. The
      findings did not vary by the level of Medicaid managed care penetration in the
      study states.

PMID- 15149476
TI  - The Prevention Index: using technology to improve quality assessment.
AB  - OBJECTIVE: To improve quality of care assessment for preventive medical services
      and reduce assessment costs through development of a comprehensive prevention
      quality assessment methodology based on electronic medical records (EMRs). DATA
      SOURCES: Random sample of 775 adult and 201 child members of a large nonprofit
      managed care system. STUDY DESIGN: Problems with current, labor-intensive quality
      measures were identified and remedied using EMR capabilities. The Prevention
      Index (PI) was modeled by assessing five-year patterns of delivery of 24
      prevention services to adult and child health maintenance organization (HMO)
      members and comparing those services to consensus recommendations and to selected
      Health Plan Employer Data and Information Set (HEDIS) scores for the HMO. DATA
      COLLECTION: Comprehensive chart reviews of 976 randomly selected members of a
      large managed care system were used to model the Prevention Index. PRINCIPAL
      FINDINGS: Current approaches to prevention quality assessment have serious
      limitations. The PI eliminates these limitations and can summarize care in a
      single comprehensive index that can be readily updated. The PI prioritizes
      services based on benefit, using a person-time approach, and separates preventive
      from diagnostic and therapeutic services. CONCLUSIONS: Current methods for
      assessing quality are expensive, cannot be applied at all system levels, and have
      several methodological limitations. The PI, derived from EMRs, allows
      comprehensive assessment of prevention quality at every level of the system and
      at lower cost. Standardization of quality assessment capacities of EMRs will
      permit accurate cross-institutional comparisons.

PMID- 15149477
TI  - The effect of smoking on years of healthy life (YHL) lost among middle-aged and
      older Americans.
AB  - OBJECTIVE: To estimate the effects of smoking on quality of life over time, using
      the Years of Healthy Life (YHL) construct. DATA SOURCES/STUDY SETTING: The Health
      and Retirement Study (HRS) survey (N=12,652) of persons 50 to 60 years old and
      the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey (N=8,124) of
      persons > or =70 years old, plus spouses regardless of age, followed from
      1992/1993 to 2000. STUDY DESIGN: Years of healthy life from baseline to death
      were estimated. Regression models were developed with smoking as the main
      explanatory variable and with both YHL and years of life remaining as the outcome
      variables. PRINCIPAL FINDINGS: Smoking was strongly and consistently related to
      YHL lost. In HRS, individuals who had quit smoking at least 15 years prior to
      baseline had a similar number of YHL left as never smokers. CONCLUSIONS: Efforts
      to encourage smoking cessation should emphasize the impact of these factors on
      quality of life.

PMID- 15149478
TI  - Alcohol drinking patterns and health care utilization in a managed care
      organization.
AB  - OBJECTIVE: To estimate the relationship between current drinking patterns and
      health care utilization over the previous two years in a managed care
      organization (MCO) among individuals who were screened for their alcohol use.
      STUDY DESIGN: Three primary care clinics at a large western MCO administered a
      short health and lifestyle questionnaire to all adult patients on their first
      visit to the clinic from March 1998 through December 1998. Patients who exceeded
      the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for
      moderate drinking were given a more comprehensive alcohol screening using a
      modified version of the Alcohol Use Disorders Identification Test (AUDIT). Health
      care encounter data for two years preceding the screening visit were linked to
      the remaining individuals who responded to one or both instruments. Using both
      quantity-frequency and AUDIT-based drinking pattern variables, we estimated
      negative binomial models of the relationship between drinking patterns and days
      of health care use, controlling for demographic characteristics and other
      variables. PRINCIPAL FINDINGS: For both the quantity-frequency and AUDIT-based
      drinking pattern variables, current alcohol use is generally associated with less
      health care utilization relative to abstainers. This relationship holds even for
      heavier drinkers, although the differences are not always statistically
      significant. With some exceptions, the overall trend is that more extensive
      drinking patterns are associated with lower health care use. CONCLUSIONS: Based
      on our sample, we find little evidence that alcohol use is associated with
      increased health care utilization. On the contrary, we find that alcohol use is
      generally associated with decreased health care utilization regardless of
      drinking pattern.

PMID- 15149479
TI  - Factors associated with physician interventions to address adolescent smoking.
AB  - OBJECTIVE: To determine the percent of adolescent Medicaid patients with medical
      record documentation about tobacco use status and cessation assistance; and
      factors associated with providers documenting and intervening with adolescent
      smokers. DATA SOURCE: Secondary analysis of data collected in 1999 from medical
      records of Wisconsin Medicaid health maintenance organization (HMO) recipients 11
      to 21 years old. STUDY DESIGN: Random reviews and data collection were related to
      visits from January 1997 to January 1999. Data collected included patient
      demographics, provider type, number of visits, and whether smoking status and
      cessation interventions were documented. DATA EXTRACTION METHODS: Medical charts
      were reviewed and a database was created using a data abstraction tool developed
      and approved by a committee to address tobacco use in Medicaid managed care
      participants. PRINCIPAL FINDINGS: Among adolescents seen by a physician from 1997
      to 1999, tobacco use status was documented in 55 percent of patient charts. Most
      often tobacco use status was documented on history and physical or prenatal
      forms. Of identified adolescent smokers, 50 percent were advised to quit, 42
      percent assisted, and 16 percent followed for smoking cessation. Pregnant
      patients were more likely to have tobacco use documented than nonpregnant
      patients (OR=10.8, 95 percent CI=4.9 to 24). The odds of documentation increased
      21 percent for every one-year increase in patient age. CONCLUSIONS: Providers
      miss opportunities to intervene with adolescents who may be using tobacco.
      Medical record prompts, similar to the tobacco use question on prenatal forms and
      the tobacco use vital sign stamp, are essential for reminding providers to
      consistently document and address tobacco use among adolescents.

PMID- 15149480
TI  - Linkage with primary medical care in a prospective cohort of adults with
      addictions in inpatient detoxification: room for improvement.
AB  - OBJECTIVE: To identify patient characteristics and health care experiences
      associated with primary care linkage after alcohol or drug detoxification. DATA
      SOURCES/STUDY SETTING: Primary data collected over two years. Subjects were
      adults without primary medical care, in an urban residential detoxification
      program. STUDY DESIGN: A prospective cohort study in the context of a randomized
      trial of a linkage intervention, and an expansion of Medicaid benefits. DATA
      COLLECTION/EXTRACTION METHODS: Data were collected by interview assessment of
      predisposing, enabling, and illness variables. Linkage was defined as self-report
      of at least one visit with a primary care clinician during follow-up. PRINCIPAL
      FINDINGS: Of 400 subjects, 63 percent linked with primary medical care. In a
      multivariable model adjusting for randomization assignment, predisposing,
      enabling, and illness variables, women, those with no recent incarceration, those
      with support for abstinence by family or friends, and those who had visited a
      medical clinic or physician recently were significantly more likely to link with
      primary care. Those with health insurance during follow-up were also more likely
      to link. Recent mental health or addictions treatment utilization and health
      status were not associated with linkage. CONCLUSIONS: A substantial proportion of
      adults with addictions do not link with primary medical care. These data suggest
      that efforts could be focused on those least likely to link, that contacts with
      mental health and addictions treatment providers are underutilized opportunities
      for these efforts, and that health policy changes such as expanding health
      insurance benefits may improve entry of substance-dependent patients into primary
      medical care.

PMID- 15149481
TI  - Use of midlevel practitioners to achieve labor cost savings in the primary care
      practice of an MCO.
AB  - OBJECTIVE: To estimate the savings in labor costs per primary care visit that
      might be realized from increased use of physician assistants (PAs) and nurse
      practitioners (NPs) in the primary care practices of a managed care organization
      (MCO). STUDY SETTING/DATA SOURCES: Twenty-six capitated primary care practices of
      a group model MCO. Data on approximately two million visits provided by 206
      practitioners were extracted from computerized visit records for 1997-2000.
      Computerized payroll ledgers were the source of annual labor costs per practice
      from 1997-2000. STUDY DESIGN: Likelihood of a visit attended by a PA/NP versus MD
      was modeled using logistic regression, with practice fixed effects, by department
      (adult medicine, pediatrics) and year. Parameter estimates and practice fixed
      effects from these regressions were used to predict the proportion of PA/NP
      visits per practice per year given a standard case mix. Least squares
      regressions, with practice fixed effects, were used to estimate the association
      of this standardized predicted proportion of PA/NP visits with average annual
      practitioner and total labor costs per visit, controlling for other practice
      characteristics. RESULTS: On average, PAs/NPs attended one in three adult
      medicine visits and one in five pediatric medicine visits. Likelihood of a PA/NP
      visit was significantly higher than average among patients presenting with minor
      acute illness (e.g., acute pharyngitis). In adult medicine, likelihood of a PA/NP
      visit was lower than average among older patients. Practitioner labor costs per
      visit and total labor costs per visit were lower (p<.01 and p=.08, respectively)
      among practices with greater use of PAs/NPs, standardized for case mix.
      CONCLUSIONS: Primary care practices that used more PAs/NPs in care delivery
      realized lower practitioner labor costs per visit than practices that used less.
      Future research should investigate the cost savings and cost-effectiveness
      potential of delivery designs that change staffing mix and division of labor
      among clinical disciplines.

PMID- 15149482
TI  - The lifetime distribution of health care costs.
AB  - OBJECTIVE: To estimate the magnitude and age distribution of lifetime health care
      expenditures. DATA SOURCES: Claims data on 3.75 million Blue Cross Blue Shield of
      Michigan members, and data from the Medicare Current Beneficiary Survey, the
      Medical Expenditure Panel Survey, the Michigan Mortality Database, and Michigan
      nursing home patient counts. DATA COLLECTION: Data were aggregated and summarized
      in year 2000 dollars by service, age, and gender. STUDY DESIGN: We use life table
      models to simulate a typical lifetime's distribution of expenditures, employing
      cross-sectional data on age- and sex-specific health care costs and the mortality
      experience of the population. We determine remaining lifetime expenditures at
      each age for all initial members of a birth cohort. Separately, we calculate
      remaining expenditures for survivors at all ages. Using cross-sectional data, the
      analysis holds disease incidence, medical technology, and health care prices
      constant, thus permitting an exclusive focus on the role of age in health care
      costs. PRINCIPAL FINDINGS: Per capita lifetime expenditure is USD $316,600, a
      third higher for females (USD $361,200) than males (USD $268,700). Two-fifths of
      this difference owes to women's longer life expectancy. Nearly one-third of
      lifetime expenditures is incurred during middle age, and nearly half during the
      senior years. For survivors to age 85, more than one-third of their lifetime
      expenditures will accrue in their remaining years. CONCLUSIONS: Given the
      essential demographic phenomenon of our time, the rapid aging of the population,
      our findings lend increased urgency to understanding and addressing the
      interaction between aging and health care spending.

PMID- 15149483
TI  - Determining personal care consumers' preferences for a consumer-directed cash and
      counseling option: survey results from Arkansas, Florida, New Jersey, and New
      York elders and adults with physical disabilities.
AB  - OBJECTIVE: To assess Medicaid consumers' interest in a consumer-directed cash
      option for personal care and other services, in lieu of agency-delivered
      services. DATA SOURCES/STUDY SETTING: Telephone survey data were collected from
      four states from April to November 1997. Postsurvey focus groups were conducted
      in four states in 1998. Early implementation experiences are drawn from three
      states from 1999 to 2002. STUDY DESIGN: Participants (N=2,140) were selected for
      a structured telephone survey interview from a probability-sampling frame of
      current Medicaid consumers in Arkansas, Florida, New Jersey, and New York. Key
      variables include interest in the cash option, demographic and background
      characteristics of consumers, as well as previous experience and training needed.
      Postsurvey focus groups were also conducted with current Medicaid consumers. DATA
      COLLECTION/EXTRACTION METHODS: Interviewers read the telephone survey from
      computer screens and entered responses directly into the database of the
      Macintosh Computer Assisted Telephone Interview software. Data were analyzed
      using SPSS 10.0 (http://www.spss.com) for Windows. PRINCIPAL FINDINGS: Cash
      option interest was positively associated with experience hiring and supervising
      workers, more severe levels of disability, having a live-in caregiver, living in
      Florida, and minority status. Age of the client was also a significant factor.
      CONCLUSIONS: There is significant interest in the cash option, although interest
      varies among subgroups of consumers. Future research should continue to evaluate
      interest in the cash option among different groups of consumers, as well as
      actual experience with the option when the Cash and Counseling Demonstration and
      Evaluation (CCDE) evaluation findings are completed.

PMID- 15149487
TI  - Introduction: cardiovascular safety and triptans in the acute treatment of
      migraine.

PMID- 15149488
TI  - Are migraine and coronary heart disease associated? An epidemiologic review.
AB  - In evaluating the cardiovascular risks of triptans (5-HT(1B/1D) agonists) for the
      treatment of migraine, the possible relationship between migraine and
      cardiovascular disease warrants careful assessment. The vascular nature of
      migraine is compatible with the possibility that migraine is a manifestation of
      cardiovascular disease or is linked to cardiovascular disease via a common
      mechanism. If so, then migraine itself--independent of the use of triptans--may
      be associated with an increased risk of cardiac events. This article considers
      the epidemiologic literature pertinent to evaluating the association of migraine
      with coronary heart disease. The research reviewed herein fails to support an
      association between migraine and coronary heart disease. First, data from several
      large cohort studies show that the presence of migraine does not increase risk of
      coronary heart disease. Furthermore, although migraineurs are generally more
      likely than nonmigraineurs to report chest pain, the presence of chest pain in
      most studies did not predict serious cardiac events such as myocardial
      infarction. That the gender- and age-specific prevalence of migraine does not
      overlap with that of coronary heart disease is also consistent with a lack of
      association between migraine and atherosclerotic cardiovascular disease. While
      migraine appears not to be associated with coronary heart disease, preliminary
      evidence suggests a possible link of migraine with vasospastic disorders such as
      variant angina and Raynaud's phenomenon. These results warrant further
      investigation in large prospective studies.

PMID- 15149484
TI  - Emergency department use among Michigan children with special health care needs:
      an introductory study.
AB  - OBJECTIVE: To describe patterns of emergency department (ED) use among children
      dual-enrolled in Medicaid and Michigan's Children's Special Health Care Services
      (CSHCS). DATA SOURCES: Individual claims and enrollment data from Michigan's
      Medicaid and CSHCS programs for the period January 1, 1998, to June 30, 1999.
      Claims data were linked with eligibility data and then used to develop a 100
      percent sample of claims for individuals enrolled in both Medicaid and CSHCS.
      STUDY DESIGN: Poisson regression analysis was used to examine the rate of ED use
      for dual-enrolled children. A time-varying hazard analysis was also used to
      examine the impact of changes over time. The key variables were gender, age,
      race, county of residence, Medicaid eligibility category, and qualifying
      diagnosis. PRINCIPAL FINDINGS: Dual-enrolled children under one year of age, and
      those with qualifying diagnoses of anemia, hemophilia, asthma, epilepsy, and
      juvenile diabetes displayed especially high rates of ED use. Significant
      geographic variation in ED use remained after controlling for qualifying
      diagnoses, race/ethnicity, and other factors. African Americans displayed higher
      rates of ED utilization than non-Hispanic whites. Supplemental Security Income
      (SSI) recipients demonstrated higher utilization than other groups. CONCLUSIONS:
      Children dually enrolled in CSHCS and Medicaid face diverse challenges of both
      poverty and chronic illness. Differences in patterns of use highlight the
      importance, but also the difficulty, of developing systems of care to manage
      complex chronic conditions in low-income populations.

PMID- 15149489
TI  - Coronary vasoconstrictor potential of triptans: a review of in vitro
      pharmacologic data.
AB  - This article reviews the in vitro pharmacology of the triptans in human isolated
      coronary arteries. As expected, based on their similar pharmacologic profiles,
      the triptans cannot be easily differentiated with respect to effects at human
      isolated coronary arteries. Furthermore, the data show that at therapeutically
      relevant concentrations, triptans have little potential to cause clinically
      significant constriction of nondiseased coronary arteries. These data, considered
      in the context of clinical findings reviewed elsewhere in this supplement,
      support the conclusion that, while all triptans have the potential to produce
      small contractions of human isolated coronary arteries, their craniovascular
      selectivity, when used at therapeutic doses, renders them unlikely to cause
      serious adverse coronary events in patients with healthy coronary arteries.

PMID- 15149490
TI  - Cardiovascular tolerability and safety of triptans: a review of clinical data.
AB  - Triptans are not widely used in clinical practice despite their well-established
      efficacy, endorsement by the US Headache Consortium, and the demonstrable need to
      employ effective intervention to reduce migraine-associated disability. Although
      the relatively restricted use of triptans may be attributed to several factors,
      research suggests that prescribers' concerns about cardiovascular safety
      prominently figure in limiting their use. This article reviews clinical data-
      including results of clinical trials, postmarketing studies and surveillance, and
      pharmacodynamic studies--relevant to assessing the cardiovascular safety profile
      of the triptans. These data demonstrate that triptans are generally well
      tolerated. Chest symptoms occurring during use of triptans are usually nonserious
      and usually not attributed to ischemia. Incidence of triptan-associated serious
      cardiovascular adverse events in both clinical trials and clinical practice
      appears to be extremely low. When they do occur, serious cardiovascular events
      have most often been reported in patients at significant cardiovascular risk or
      in those with overt cardiovascular disease. Adverse cardiovascular events also
      have occurred, however, in patients without evidence of cardiovascular disease.
      Several lines of evidence suggest that nonischemic mechanisms are responsible for
      sumatriptan-associated chest symptoms, although the mechanism of chest symptoms
      has not been determined to date. Importantly, most of the clinical trials and
      clinical practice data on triptans are derived from patients without known
      cardiovascular disease. Therefore, the conclusions of this review cannot be
      extended to patients with cardiovascular disease. The cardiovascular safety
      profile of triptans favors their use in the absence of contraindications.

PMID- 15149491
TI  - Cardiovascular risk assessment and triptans.
AB  - Identifying the patient for whom triptans are contraindicated because of
      recognized, diagnosed cardiovascular disease is relatively straightforward.
      Determining whether a patient with potential unrecognized cardiovascular disease
      is an appropriate candidate for triptan therapy, however, constitutes a difficult
      challenge, especially in the absence of a framework for workup of patients. This
      article discusses the pathophysiology of coronary heart disease and issues
      involved in assessing cardiovascular risk, and it attempts to provide a framework
      for cardiovascular risk assessment that can be applied to decisions for
      prescribing triptans. Current guidelines for cardiovascular risk assessment allow
      stratification of patients to low, intermediate, or high risk of coronary heart
      disease events. This framework for risk assessment can be applied to decisions
      for prescribing triptans. Cardiovascular risk-assessment algorithms discussed
      elsewhere in this supplement suggest that patients at low risk (1 or no risk
      factors) of coronary heart disease can be prescribed triptans without the need
      for a more intensive cardiovascular evaluation. Conversely, patients with
      established coronary heart disease or coronary heart disease risk equivalents
      should not be prescribed triptans according to the current prescribing
      recommendations. Patients at intermediate risk (2 or more risk factors) of
      coronary heart disease require cardiovascular evaluation before triptans can be
      prescribed. Current understanding suggests that the risk of future acute coronary
      events is a function of the absolute number of vulnerable plaques present, a
      variable that cannot be accurately determined using available technology or risk
      prediction models. Cardiovascular risk-assessment guidelines should be evaluated
      in the context of this limitation.

PMID- 15149492
TI  - Calcium pumps and keratinocytes: lessons from Darier's disease and Hailey-Hailey
      disease.
AB  - Darier's disease and Hailey-Hailey disease are autosomal dominantly inherited
      skin disorders in which desmosomal adhesion between keratinocytes is abnormal.
      ATP2A2 and ATP2C1 have been identified as the causative genes for Darier's
      disease and Hailey-Hailey disease, respectively. ATP2A2 encodes the
      sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2) pump, while ATP2C1
      encodes a secretory pathway Ca(2+)/Mn(2+)-ATPase (SPCA1) found in the Golgi
      apparatus. We review recent work into the function of these pumps in human
      keratinocytes and discuss how mutations in these genes might cause these diseases
      by altering the formation or stability of desmosomes.

PMID- 15149493
TI  - Exfoliative cytology as a diagnostic test for basal cell carcinoma: a meta
      analysis.
AB  - BACKGROUND: Exfoliative cytology is only occasionally used in clinical practice
      to diagnose basal cell carcinoma (BCC). OBJECTIVES: To systematically review the
      literature examining exfoliative cytology as a diagnostic tool for BCC and to
      meta-analytically summarize the accuracy of this test. METHODS: Diagnostic test
      meta-analysis. A computerized database search was made of MEDLINE (1966-2000) and
      EMBASE (1950-2000) using appropriately indexed terms. Hand searches of relevant
      journals were made. Bibliographies of relevant articles were further explored.
      Histopathology was used as the reference standard. A summary receiver-operating
      characteristic curve analysis was performed using the statistical package Meta
      Test version 0.6 (J. Lau, New England Medical Center, Boston, MA, U.S.A., 1997).
      RESULTS: Eight primary studies (seven English language and one Italian language)
      fulfilled the inclusion criteria. The pooled sample included 1261 BCCs. These
      studies varied greatly in methodological quality and were, in general, poor. A
      meta-analysis showed the pooled sensitivity to be high at 97%[95% confidence
      interval (CI) 94-99]. Consequently, only 3% of BCCs included were misdiagnosed as
      non-BCC by cytology. The corresponding pooled specificity was 86% (95% CI 80-91).
      CONCLUSIONS: Exfoliative cytology probably has a high diagnostic accuracy for
      BCC. However, large, better designed and better reported studies are needed to
      ascertain the true accuracy of this technique. In the interim, this test should
      be considered in specific subgroups of patients in whom even a 2-mm punch biopsy
      may be considered inappropriate, e.g. a cosmetically sensitive site in a young
      person. Similarly, it should be considered when a BCC is to be treated without a
      diagnostic biopsy being taken, e.g. with cryotherapy.

PMID- 15149494
TI  - Refinement of a locus for Marie Unna hereditary hypotrichosis to a 1.1-cM
      interval at 8p21.3.
AB  - BACKGROUND: Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal
      congenital alopecia with progressive hair loss starting in early childhood and
      accelerating at puberty. A locus for MUHH has been mapped on chromosome 8p21 but
      no genes for MUHH have been identified to date. OBJECTIVES: To refine the MUHH
      locus to a narrow chromosome region to facilitate cloning of the gene. METHODS:
      We performed genotyping and linkage analysis in a multigeneration Chinese family
      with MUHH, using 18 high-density microsatellite markers spanning the previously
      mapped interval at 8p21. RESULTS: Significant evidence for linkage was observed
      in this region, with a maximum two-point LOD score of 3.01 (theta = 0). Haplotype
      analysis localized the MUHH locus within the region defined by D8S282 and
      D8S1839. This region overlaps by 1.1-cM with the previously reported MUHH region
      and represents a physical distance of about 380 kb. CONCLUSIONS: This study
      provides a refined map location (1.1 cM) for isolation of the gene causing MUHH.
      These data also indicate the existence of a common MUHH locus at 8p21.3 between
      affected caucasian and Chinese families.

PMID- 15149496
TI  - Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin
      zone of spreading psoriatic lesions in contrast to cells expressing natural
      killer receptors, which appear late.
AB  - BACKGROUND: An influx of immunocytes, increased epidermal proliferation and
      abnormal keratinization are hallmarks of the psoriatic lesion. T-lymphocyte
      subsets in particular activated effector memory T cells and natural killer (NK) T
      cells have been suggested to play an important role in the pathogenesis of
      psoriasis. OBJECTIVES: In the present study we investigated the number of T-cell
      subsets (CD4, CD8, CD45RO, CD45RA, CD2, CD25), cells expressing NK receptors
      (CD94 and CD161), the proliferation marker Ki67 and the keratinization marker
      keratin (K10) across the margin of the spreading psoriatic plaque: distant
      uninvolved skin, the outer margin (immediately outside the clinical edge), the
      inner margin (immediately inside the clinical edge) and the central area.
      PATIENTS AND METHODS: Eight patients with active psoriasis vulgaris participated
      in this study. Biopsies were taken from the spreading psoriatic lesion from the
      distant uninvolved skin, the outer margin, the inner margin and the central area.
      Biopsies were processed for immunohistochemical staining. RESULTS: In the outer
      margin CD8+ (cytotoxic T cells) and CD45RO+ (memory effector T cells) T
      lymphocytes invade the epidermis and in this early stage the activation markers
      CD2 and CD25 also show a substantial increase. The next phase, from the outer to
      the inner margin, shows a statistically significant increase of these markers,
      and especially, the cells expressing NK receptors (CD94 and CD161) show a massive
      increase together with a significant increase of epidermal proliferation (Ki67)
      and a decrease of the K10+ epidermal surface. CONCLUSIONS: CD8+, CD45RO+, CD2+
      and CD25+ T cells have a role in the early phase of the psoriatic process,
      whereas CD94- and CD161-expressing cells together with epidermal proliferation
      and keratinization are involved in a later phase.

PMID- 15149495
TI  - Epidermolysis bullosa acquisita sera react with distinct epitopes on the NC1 and
      NC2 domains of type VII collagen: study using immunoblotting of domain-specific
      recombinant proteins and postembedding immunoelectron microscopy.
AB  - BACKGROUND: The sera of epidermolysis bullosa acquisita (EBA) react with type VII
      collagen, a major component of anchoring fibrils, in which the major epitopes
      have been considered to be present in the N-terminal noncollagenous (NC) 1
      domain. OBJECTIVES: To determine whether there are also epitopes in the C
      terminal NC2 domain, and to determine their ultrastructural localization.
      METHODS: Immunoblotting using recombinant proteins of the NC1 and NC2 domains of
      type VII collagen, and postembedding immunoelectron microscopy. RESULTS: Twenty
      of 28 EBA sera tested reacted with the NC1 domain and eight sera reacted with the
      NC2 domain. The sera that reacted with the NC1 domain showed immunoreactivity
      within the lamina densa and the sera that reacted with the NC2 domain showed
      immunoreactivity in the dermis 300-360 nm below the lamina densa. CONCLUSIONS:
      This study clearly identified the presence of epitopes in the NC2 domain, and
      showed that the epitope in the NC1 domain is present in the lamina densa and that
      the epitope in the NC2 domain is in the dermis below the lamina densa.

PMID- 15149497
TI  - Human follicular stem cells: their presence in plucked hair and follicular cell
      culture.
AB  - BACKGROUND AND OBJECTIVES: A considerable portion of the hair follicle remains
      attached to plucked hair and can be used for follicle cell culture. In this study
      we have phenotyped these cells in an attempt to identify the stem cell fraction.
      Reports in the literature have indicated that this cell population may be
      positive for cytokeratin (CK) 19. Because stem cells in general need to be
      protected from apoptosis, the presence of the apoptosis-suppressing Bcl-2
      protein, together with the absence of the apoptosis-promoting Bax and the CK
      profile may be used as an indicator of the stem cell population in the hair
      follicle, and in cultures of hair follicle cells. METHODS: Hair follicles from
      skin biopsies and plucked hair were derived from the scalps of healthy
      volunteers. Follicular cells were cultured from the plucked hairs. These hair
      follicles, plucked hairs and cultured cells were examined for their CK profiles,
      which are indicative of the type of cell (basal/stem cells) and for their status
      with respect to the proliferation marker Ki-67, Bax and Bcl-2. RESULTS: We found
      coexpression for CK19 and Bcl-2, but not Bax in two distinct areas, localized in
      the upper and lower third of the follicle from both skin biopsies and plucked
      hairs, while proliferation markers were negative in these areas. CK19 and Bcl-2
      were also coexpressed in combination in a fraction of the follicular cell
      culture. The skin basal cell marker CK14 could be found throughout the outer root
      sheath of the hair follicle from both skin biopsies and plucked hairs, as well as
      in the follicular cell culture. CONCLUSIONS: Thus, CK19/Bcl-2-positive and Bax
      negative cells can be obtained from cells derived from plucked hair and are
      retained in cultures made from these cells. If this phenotype represents
      follicular stem cells, our finding endorses the assumption that stem cells are
      located in the bulge area of the hair follicle, as we did not find them in or
      near the dermal papilla.

PMID- 15149498
TI  - Microfabricated silicon microneedles for nonviral cutaneous gene delivery.
AB  - BACKGROUND: The skin represents an accessible somatic tissue for therapeutic gene
      transfer. The superficial lipophilic layer of the skin, the stratum corneum,
      however, constitutes a major obstacle to the cutaneous delivery of charged
      macromolecules such as DNA. OBJECTIVES: To determine whether silicon-based
      microneedles, microfabricated via a novel isotropic etching/BOSCH reaction
      process, could generate microchannels in the skin of sufficient dimensions to
      facilitate access of lipid : polycation : pDNA (LPD) nonviral gene therapy
      vectors. METHODS: Scanning electron microscopy was used to visualize the
      microconduits created in heat-separated human epidermal sheets after application
      of the microneedles. Following confirmation of particle size and particle surface
      charge by photon correlation spectrocopy and microelectrophoresis, respectively,
      the diffusion of fluorescent polystyrene nanospheres and LPD complexes through
      heat-separated human epidermal sheets was determined in vitro using a Franz-type
      diffusion cell. In-vitro cell culture with quantification by flow cytometry was
      used to determine gene expression in human keratinocytes (HaCaT cells). RESULTS:
      The diffusion of 100 nm diameter fluorescent polystyrene nanospheres, used as a
      readily quantifiable predictive model for LPD complexes, through epidermal sheets
      was significantly enhanced following membrane treatment with microneedles. The
      delivery of LPD complexes either into or through the membrane microchannels was
      also demonstrated. In both cases considerable interaction between the particles
      and the epidermal sheet was observed. In-vitro cell culture was used to confirm
      that LPD complexes mediated efficient reporter gene expression in human
      keratinocytes in culture when formulated at the appropriate surface charge.
      CONCLUSIONS: These studies demonstrate the utility of silicon microneedles in
      cutaneous gene delivery. Further studies are required to elucidate fully the
      influence of the physicochemical characteristics of gene therapy vectors, e.g.
      particle diameter and surface charge, on their diffusion through microchannels
      and to quantify gene expression in vivo.

PMID- 15149499
TI  - Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1
      mutations is associated with contrasting perturbations of desmosomes and the
      keratin filament network.
AB  - BACKGROUND: Several hereditary human diseases are now known to be caused by
      distinct mutations in genes encoding various desmosome components. Although the
      effects of some of these mutant genes have been analysed by targeted disruption
      experiments in mouse models, little is known about the cell and tissue changes in
      affected human patients. OBJECTIVES: To investigate the effects of heterozygous
      nonsense mutations in desmoplakin (Dp) and desmoglein (Dsg) 1 which cause the
      autosomal dominant disorder striate palmoplantar keratoderma (SPPK), focusing on
      changes in desmosome structure and composition and the associated keratin
      intermediate filament (KIF) network in palm skin, and in cultured keratinocytes
      generated from the same site. METHODS: We analysed palm and nonpalm skin sections
      from four SPPK patients with Dp mutations and one patient with a Dsg1 mutation
      with respect to tissue and subcellular morphologies, and correlated the in vivo
      and in vitro findings. RESULTS: Using electron microscopy, we found abnormalities
      of desmosomes and cell-cell adhesion in the suprabasal layers in the epidermis
      from patients with both Dsg1- and Dp-associated SPPK. These changes were more
      advanced in skin from patients with Dp mutations. Both Dp and Dsg1 mutations were
      accompanied by significantly reduced numbers of desmosomes in the suprabasal
      layers, while decreased desmosome size was evident only in Dsg1-associated SPPK.
      Confocal microscopy analysis showed marked differences in the expression of
      keratins and of desmosome components, both between the two types of SPPK, and
      between SPPK and normal skin. The expression of keratins K5, K14 and K10 was
      reduced in Dsg1-associated SPPK skin, whereas perinuclear aggregation of keratin
      filaments was more evident in Dp-associated SPPK. In both types of SPPK
      upregulation of K16 was pronounced and involucrin labelling was abnormal.
      CONCLUSIONS: Mutations in Dp and Dsg1 genes causing SPPK may be associated with
      perturbations in epidermal differentiation accompanied by a marked disruption of
      several components of the epidermal scaffold including desmosomes and the KIF
      network.

PMID- 15149500
TI  - Effective treatment of chondrodermatitis nodularis chronica helicis using a
      conservative approach.
AB  - BACKGROUND: Chondrodermatitis nodularis chronica helicis (CNCH) is usually
      treated by surgical excision, but is prone to recurrence. OBJECTIVES: To examine
      whether CNCH could be treated nonsurgically using a home-made, pressure-relieving
      prosthesis. METHODS: A retrospective comparison was made of the outcome in 41
      subjects treated surgically and 15 treated nonsurgically between 1999 and 2001.
      RESULTS: Thirteen of the 15 patients (87%) treated nonsurgically were healed at
      follow-up after 1 month of conservative treatment and so have avoided surgery to
      date. In contrast, the recurrence rate of the surgically treated group was 14 of
      41 (34%) patients. CONCLUSIONS: As a result of this study, we recommend that
      patients presenting with CNCH be managed conservatively in the first instance.

PMID- 15149501
TI  - Association between melanoma and dermal mast cell prevalence in sun-unexposed
      skin.
AB  - BACKGROUND: Both exposure to intermittent intense sunlight during childhood and
      ultraviolet (UV) radiation-induced immunomodulation have been directly associated
      with melanoma development. In mice, the prevalence of dermal mast cells
      determines susceptibility to UVB-induced systemic suppression of contact
      hypersensitivity responses and thus may affect immunological responses to
      melanoma antigens. OBJECTIVES: To determine the relevance of murine studies of
      dermal mast cell prevalence to human melanoma pathogenesis. METHODS: The
      prevalence of mast cells was examined in sun-unexposed buttock skin of 45
      melanoma patients and 68 control volunteers who had no history of skin cancer
      development. Buttock skin was studied because mast cell prevalence is stable with
      ageing and the confounding effects of environmental UV exposure are minimized.
      RESULTS: Using tissue immunostaining, the buttock skin from melanoma patients had
      a significantly higher dermal mast cell prevalence (mean +/- SEM 38 +/- 2 mast
      cells mm(-2)) than controls (32 +/- 2 mast cells mm(-2)) (P = 0.02). Analysis by
      binary logistic regression showed that the association between mast cell
      prevalence and melanoma outcome was not significantly altered by skin phototype.
      CONCLUSIONS: The immunomodulatory effects of mast cell products in UV-irradiated
      skin may contribute significantly to the initiation and development of human
      cutaneous malignant melanoma.

PMID- 15149502
TI  - Involvement of granulysin-producing T cells in the development of superficial
      microbial folliculitis.
AB  - BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed
      on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown
      that granulysin contributes to the defence mechanisms against mycobacterial
      infection. Superficial microbial folliculitis is a common skin disease. In a
      previous report, we showed that, as a first line of defence, alpha-defensin, a
      human neutrophil peptide, and beta-defensin (human beta-defensin-2) were
      expressed in infiltrating neutrophils and in lesional epidermal keratinocytes,
      respectively, in superficial folliculitis. As we also observed many infiltrating
      lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may
      possess antimicrobial substances, such as granulysin, and play a role in the
      defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of
      superficial microbial folliculitis diagnosed clinically and histologically were
      examined by means of immunohistochemistry. To identify the phenotype of cells
      expressing granulysin, confocal laser microscopic examination was performed.
      RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the
      perivascular regions. A large number of these lymphoid cells were positive for
      granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and
      UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic
      examination with a confocal laser showed that the lymphocytes producing
      granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We
      showed that many granulysin-bearing T cells infiltrated affected follicles and
      perilesional dermis in superficial microbial folliculitis. However, few
      granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our
      observations indicated that adaptive immunity such as granulysin, a lymphocyte
      produced antimicrobial protein, may play an important role in the cutaneous
      defence mechanism.

PMID- 15149503
TI  - Tumour necrosis factor-alpha but not interferon-gamma is the main inducer of
      inducible protein-10 in skin fibroblasts from patients with atopic dermatitis.
AB  - BACKGROUND: Inducible protein (IP)-10 belongs to the CXC chemokine subfamily and
      acts through the CXCR3 receptors that attract T lymphocytes. Keratinocytes are
      thought to be the main cell source of this chemokine in the skin, but other
      sources need to be elucidated. OBJECTIVES: To determine whether skin fibroblasts,
      besides keratinocytes, are able to produce IP-10 and the possible involvement of
      these cells in pathogenesis of atopic dermatitis (AD). METHODS: We studied the
      production pattern of IP-10 in dermal fibroblasts obtained from healthy donors,
      AD patients and in the HaCaT cell line (normal human keratinocytes) used as
      control. We stimulated fibroblasts after the sixth and seventh passage with
      tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-4,
      and by means of reverse transcriptase-polymerase chain reaction and enzyme-linked
      immunosorbent assay analysis detected the production pattern of IP-10. To
      determine whether a different pattern of production of IP-10 by fibroblasts
      corresponds to the level of this chemokine in the plasma of patients with AD, we
      also checked the plasma IP-10 levels in 33 AD patients and 10 healthy donors.
      RESULTS: The pattern of chemokine production between dermal fibroblasts and HaCaT
      cells was different. The main inducer of IP-10 in fibroblasts was TNF-alpha,
      whereas IFN-gamma was the main inducer of IP-10 in HaCaT cells. We demonstrate
      that fibroblasts from AD patients have higher IP-10 expression and are more
      sensitive to TNF-alpha stimulation compared with healthy controls. Consequently,
      IP-10 levels in plasma of AD patients were higher than in healthy donors.
      CONCLUSIONS: Skin fibroblasts could be an important source of IP-10. TNF-alpha is
      the main inducer of IP-10 by skin fibroblasts, but not IFN-gamma or IL-4. The
      increased level of IP-10 in the plasma of patients with AD could be connected
      with increased activity of skin fibroblasts.

PMID- 15149504
TI  - The inflammatory response in mild and in severe psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. The
      inflammatory response represents a fundamental ability of the organism to protect
      itself from infectious agents and from injury. OBJECTIVES: To evaluate the
      inflammatory response in mild and in severe psoriasis, to evaluate the endogenous
      systems counterbalancing the deleterious effects of the inflammation products,
      and to establish values of prognostic significance. METHODS: The study was
      performed in a control group (n = 40) and in 60 patients with psoriasis vulgaris,
      half presenting with mild psoriasis, and the other half with severe psoriasis. We
      evaluated total and differential leucocyte count; elastase, lactoferrin and lipid
      peroxidation as markers of neutrophil activation; total plasma antioxidant
      capacity (TAS), transferrin, ceruloplasmin, alpha(1)-antitrypsin and alpha(2)
      macroglobulin as markers of the endogenous antioxidant and antiprotease systems;
      and fibrinogen, erythrocyte sedimentation rate, C-reactive protein (CRP),
      haptoglobin, C3 and C4 complement proteins as markers of inflammation. RESULTS:
      Our data suggested that psoriasis is an inflammatory condition in which
      neutrophils seem to play a crucial role by contributing to the development of
      oxidative and proteolytic stress. The worsening of the disease seemed to be
      linked to the enhancement of the inflammatory response and of the imbalance
      between neutrophil activation products and their inhibitors. CONCLUSIONS: We
      propose values for elastase, CRP, elastase/alpha(2)-macroglobulin,
      elastase/alpha(1)-antitrypsin, thiobarbituric acid/TAS and elastase/neutrophil
      ratios with prognostic significance for the worsening of psoriasis.

PMID- 15149505
TI  - A high prevalence of sensitization still persists in leg ulcer patients: a
      retrospective series of 106 patients tested between 2001 and 2002 and a meta
      analysis of 1975-2003 data.
AB  - BACKGROUND: Sensitization to topical treatments used in leg ulcers is common.
      Questioning and patch testing are used to identify causative drugs or dressings.
      OBJECTIVES: To study the current frequency of sensitization in our centre, to
      analyse previously published studies, and to compare sensitization in recent
      years with studies published before 1990. METHODS: A retrospective study was
      undertaken of all patients admitted with leg ulcers in 2001 and 2002. Of the
      files of 235 patients with leg ulcers reviewed, we identified 106 patients (group
      A) who had been patch tested in our institution between 2001 and 2002 with the
      European standard series and an additional series. The frequency of sensitization
      was compared with an earlier unpublished retrospective study in our centre of 36
      leg ulcer patients tested in 1988 (group B), with a group of unselected contact
      dermatitis patients tested between 1 January 1997 and 31 December 2000 in our
      centre (group C), and with results published in the literature. We performed a
      computerized database search of MEDLINE and compared results obtained in recent
      years with those obtained before 1990 to obtain evidence of changing trends.
      RESULTS: Seventy-five per cent of the 106 patients had at least one positive
      reaction, and 57% had two or more positive reactions. Balsam of Peru was positive
      in 40% of cases, followed by lanolin (21%), fragrance mix (18%), trichlocarban
      (13%), colophony (11%), Cetavlon (cetrimide cream) (9%) and neomycin (9%). Thirty
      five of the 36 group B patients had at least one positive reaction. Lanolin was
      the most frequent (31%), followed by balsam of Peru (22%), Cetavlon (19%),
      colophony (14%), terebenthene (14%), quinoline mix (11%) and benzocaine (8%). Two
      hundred and eighty-six of 526 patients of group C were positive in at least one
      test (54.4%). Three allergens gave a sensitization rate >10%: balsam of Peru
      (12.5%), fragrance mix (15.2%) and nickel sulphate (21.1%). Review of the
      literature and calculation of sensitization rates in a pool of 3043 patients
      extracted from 24 series, plus our own, showed persistence of high sensitization
      rates and a significant (8.5%) increase in sensitization between the two periods
      compared. There was a decrease in sensitivity to lanolin, constant sensitization
      to aminoglycosides, a slight increase in sensitivity to thiuram mix and
      glucocorticoids, and a marked increase in sensitivity to balsam of Peru in
      France. Newer topical treatments and dressings showed very low rates of
      sensitivity with the exception of hydrogels. CONCLUSIONS: Despite warnings,
      sensitization to topical treatments for leg ulcers is still frequent and,
      moreover, continues to increase, some variations reflecting local nursing
      practices and variations in topical treatment available. Although a decrease in
      sensitization rate with lanolin has been observed throughout the world, no
      decrease in sensitization rate has been demonstrated with aminoglycosides, and
      sensitization to glucocorticoids, thiuram mix and new products (hydrogels) is now
      increasingly being reported.

PMID- 15149506
TI  - Nonablative laser treatment of wrinkles: meeting the objective? Assessment by 25
      dermatologists.
AB  - BACKGROUND: Established skin resurfacing methods causing superficial wounds and
      extended recovery times have become less popular since the introduction of
      nonablative lasers. OBJECTIVES: To evaluate the clinical efficacy of a
      nonablative 1450-nm diode laser system. METHODS: Nine patients (Fitzpatrick skin
      type II-IV) with periorbital wrinkling class I-II were treated three times at 3
      weekly intervals with a 1450-nm diode laser. Clinical outcome was determined by
      25 independent dermatologists evaluating standardized photographs taken before
      treatment and 1 month after treatment. RESULTS: The patients were satisfied with
      the procedure, and reported a mild to moderate improvement in all cases. Among 25
      dermatologists, only two provided ratings which were significantly in favour of a
      positive treatment effect. CONCLUSIONS: Nonablative laser treatment subjectively
      satisfies patients but does not convince objective judgement.

PMID- 15149507
TI  - Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin
      and p16) and CCL27 in alopecia areata before and after diphencyprone treatment:
      an immunohistochemical study.
AB  - BACKGROUND: Alopecia areata (AA) is a relatively common inflammatory form of
      nonscarring hair loss of unknown pathogenesis, but possibly of autoimmune origin.
      Topical immunotherapy, using a potent contact allergen such as diphencyprone
      (DPC), is currently considered the most effective mode of treatment. However, the
      way in which DPC operates on hair follicles in AA still remains to be elucidated.
      Vascular endothelial growth factor (VEGF), essential for angiogenesis and
      vascular permeability, may be responsible for maintaining proper vasculature
      around hair follicles, and several studies provide evidence that apoptosis is a
      central element in the regulation of hair follicle and vascular regression. The
      cutaneous lymphocyte-associated antigen (CLA) and the skin-associated chemokine
      CCL27 highlight an important role for epithelial cells in controlling homeostatic
      lymphocyte trafficking. OBJECTIVES: To determine the expression pattern of VEGF,
      factor (F)VIII, survivin, p16, CD4, CD8, CLA and CCL27 in alopecic skin before
      and after treatment with DPC. Methods Immunohistochemical staining methods were
      applied to skin biopsy specimens obtained from alopecic areas of 14 patients
      before and after DPC treatment and from five healthy subjects. Sections were
      incubated with monoclonal antibodies against VEGF, FVIII, survivin, p16, CCL27,
      CLA, CD4 and CD8, and their immunohistochemical expression was evaluated by light
      microscopy. RESULTS: The intensity of VEGF staining in alopecic human hair
      follicles was significantly lower than in healthy scalp tissue. FVIII
      immunostaining showed a significantly reduced development of the microvasculature
      in AA in comparison with healthy scalp tissue. After DPC therapy, cells of
      alopecic hair follicles showed a significant increase of VEGF immunopositivity,
      and the number of capillary vessels expressing FVIII was markedly increased in
      comparison with untreated scalp tissue. The increase in microvessels was
      associated with strong survivin expression in endothelial cells after treatment.
      All alopecic specimens showed expression of p16 in the hair follicle outer root
      sheath (ORS), with a significant increase after therapy. After treatment we
      observed a significantly decreased number of CD4+ cells and an increase of CD8+
      cells (CD4/CD8 ratio 0.85) in alopecic skin compared with untreated scalp tissue
      (CD4/CD8 ratio 3.45). Most of the T lymphocytes found in inflammatory skin
      lesions expressed CLA antigen and after therapy we observed a significantly
      higher CLA positivity in hair follicles (50% or more) in comparison with
      untreated alopecic scalp tissue. Alopecic patients showed a CCL27
      immunopositivity significantly lower than in normal scalp tissue. After DPC
      therapy the labelling intensity for CCL27 showed a significant increase both in
      the ORS and in the inner root sheath; similarly, in the basal interfollicular
      keratinocytes we observed a moderate increase in CCL27 expression. CONCLUSIONS:
      Topical immunotherapy exerts an important role in angiogenesis, upregulating VEGF
      in human hair follicle keratinocytes and upregulating survivin to preserve
      endothelial cell viability. Moreover, it considerably alters the peribulbar
      CD4/CD8 ratio, restoring a condition close to normal scalp skin. Our study could
      contribute to explaining some aspects of AA pathogenesis that are still unknown
      and aid understanding of how DPC could act in this complex disease.

PMID- 15149509
TI  - Human T-cell leukaemia/lymphoma virus type 1-associated infective dermatitis in
      Africa: a report of five cases from Senegal.
AB  - BACKGROUND: Infective dermatitis (ID) is a rare dermatological condition of
      childhood that has been linked to human T-cell leukaemia/lymphoma virus type 1
      (HTLV-1). Most cases have been reported in the Caribbean. Although several
      million people are estimated to be infected by HTLV-1 in sub-Saharan Africa, no
      case of ID has been reported in this area. OBJECTIVES: To identify and to
      describe cases of HTLV-1-associated ID in Senegal, West Africa. METHODS: Over a 3
      year period, a serological test for HTLV-1 was performed at a dermatological
      centre in Dakar, Senegal, in children who presented with a picture suggestive of
      ID. Complementary haematological, immunological and virological investigations
      were performed in infected children and in their mothers. RESULTS: Five patients
      with typical HTLV-1-associated ID were identified, of ages 17, 5, 4, 3 and 3
      years; two patients belonged to the same family. They all presented with repeated
      flares of superinfected dermatitis involving typical sites of ID (mainly the
      scalp, external ears, nares and eyelids), associated with nasal discharge, and
      less commonly with a nonspecific papular rash on the face or trunk. Although oral
      antibiotic therapy always gave effective control of the symptoms, recurrences
      were constant. A persisting dry dermatitis of the retroauricular folds was common
      between flares. Infection in the oldest patient was associated with a chronic
      adult T-cell leukaemia/lymphoma. The mothers of three patients, and the
      grandmother of another, were all infected by HTLV-1 strains belonging to the
      Cosmopolitan molecular subtype, with a perfect nucleotide identity of long
      terminal repeat and env gp21 genomic regions within each family. CONCLUSIONS: We
      present the clinical and virological features of the first reported African cases
      of HTLV-1-associated ID. When compared with data from the Caribbean, infectious
      features seemed particularly prominent. ID appears to be overlooked in sub
      Saharan Africa, where it might be easily confused with common pyoderma. Breast
      feeding appears to be the origin of HTLV-1 contamination of the children.

PMID- 15149508
TI  - Increased risk of skin cancer associated with the presence of epidermodysplasia
      verruciformis human papillomavirus types in normal skin.
AB  - BACKGROUND: Human papillomaviruses (HPVs) are found in normal skin and in benign
      and malignant skin conditions. Epidermodysplasia verruciformis (EV) HPV types are
      those most plausibly linked to the development of squamous cell carcinomas of the
      skin. OBJECTIVES: To assess the risk of nonmelanoma skin cancer (NMSC) associated
      with the presence of EV HPV in normal skin in immunocompetent (IC) individuals
      and renal transplant recipients (RTRs). METHODS: Using a degenerate and nested
      polymerase chain reaction technique, HPV DNA was sought in 124 normal skin
      samples from sun-exposed and nonsun-exposed sites, from 39 IC individuals and 38
      RTRs, both with and without NMSC. Data were analysed using the Mantel-Haenszel
      test and by logistic regression analysis. RESULTS: HPV DNA was detected in 58/67
      (87%) and 20/57 (35%) samples from renal transplant and IC patients,
      respectively. There was no difference in either the prevalence or spectrum of HPV
      types found in sun-exposed and nonsun-exposed normal skin. However, there was
      significant association between NMSC and the presence of EV HPV DNA. Multivariate
      analysis provided an odds ratio of 6.41 (95% confidence interval 1.79-22.9) for
      the association of EV HPV DNA in normal skin (irrespective of site) and NMSC
      status, even after stratifying for patient group and adjusting for the clustering
      effect of multiple sampling. Conversely, there was no association between skin
      cancer status and the presence of cutaneous or mucosal HPV types in either sun
      exposed or nonsun-exposed skin. CONCLUSIONS: HPV DNA is widespread in normal
      adult skin, particularly in transplant patients. In our study, the presence of EV
      but not cutaneous HPV DNA in normal skin was significantly associated with NMSC
      status and may prove to be of predictive value for skin cancer risk. These data
      provide reason to focus on EV HPV types as causal agents in skin cancer.

PMID- 15149510
TI  - The effect of inositol supplements on the psoriasis of patients taking lithium: a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Lithium carbonate is the most widely used long-term treatment for
      bipolar affective disorders, but its ability to trigger and exacerbate psoriasis
      can become a major problem in patients for whom lithium is the only treatment
      option. Inositol depletion underlies the action of lithium in bipolar affective
      disorders and there are good theoretical reasons why the use of inositol
      supplements might be expected to help this group of patients. OBJECTIVES: To
      determine whether inositol supplements improve the psoriasis of patients on
      lithium therapy. METHODS: Fifteen patients with psoriasis, who were taking
      lithium, took part in a randomized, double-blind, placebo-controlled, crossover
      clinical trial comparing the effect of inositol supplements with those of a
      placebo (lactose). Changes in the severity of their psoriasis were measured by
      Psoriasis Area and Severity Index scores recorded before and after the different
      courses of treatment. The effect of inositol supplements on the psoriasis of 11
      patients who were not taking lithium was evaluated in the same way. RESULTS: The
      inositol supplements had a significantly beneficial effect on the psoriasis of
      patients taking lithium. No such effect was detected on the psoriasis of patients
      not on lithium. CONCLUSIONS: The use of inositol supplements is worth considering
      for patients with intractable psoriasis who need to continue to take lithium for
      bipolar affective disorders.

PMID- 15149511
TI  - Leflunomide in the treatment of psoriasis: results of a phase II open trial.
AB  - BACKGROUND: Psoriasis is recognized as the most prevalent T-cell-mediated
      inflammatory disease in humans, with predominantly activated T-helper (Th) 1 cell
      effectors. Leflunomide exerts its anti-inflammatory activities by preventing the
      generation of proinflammatory Th1 effectors and promoting Th2 cell
      differentiation. OBJECTIVES: To determine the safety and efficacy of leflunomide
      in patients with moderate to severe plaque-type psoriasis. METHODS: In an open
      label phase II trial, eight patients with psoriasis received oral leflunomide 20
      mg daily for 12 weeks. Patients were evaluated for improvement in psoriasis,
      quality of life, histological changes and toxicity. RESULTS: Antipsoriatic
      effects were obtained in all but two patients. A significant decrease was
      observed in the mean +/- SD Psoriasis Area and Severity Index score, from 20.08
      +/- 6.85 before treatment to 12.51 +/- 11.83 after (P = 0.03). The antipsoriatic
      efficiency was confirmed histologically, with a significant mean +/- SD decrease
      in epidermal thickness, from 0.73 +/- 0.19 micro m before to 0.31 +/- 0.16 microm
      after (P = 0.01). The quality of life score showed an improvement, from 8.58 +/-
      2.38 (mean +/- SD) before to 5.33 +/- 1.95 after (P = 0.02). The treatment was
      well tolerated; adverse reactions primarily consisted of transitory
      gastrointestinal events. CONCLUSIONS: Our data suggest that leflunomide for
      plaque-type psoriasis is a safe and clinically effective option as monotherapy.
      However, double-blind, placebo-controlled studies are needed.

PMID- 15149512
TI  - Topical vitamin B12--a new therapeutic approach in atopic dermatitis-evaluation
      of efficacy and tolerability in a randomized placebo-controlled multicentre
      clinical trial.
AB  - BACKGROUND: Vitamin B(12) is an effective scavenger of nitric oxide (NO). As the
      experimental application of a NO synthase inhibitor, N omega-nitro-L-arginine,
      led to a clear decrease in pruritus and erythema in atopic dermatitis, it would
      be reasonable to assume a comparable effect of vitamin B(12). OBJECTIVES: The
      efficacy and tolerability of a new vitamin B(12) cream as a possible alternative
      to current therapies was examined. METHODS: A prospective, randomized and placebo
      controlled phase III multicentre trial, involving 49 patients was conducted. For
      the treatment duration of 8 weeks, each patient applied twice daily (in the
      morning and evening) the vitamin B(12)-containing active preparation to the
      affected skin areas of one side of the body and the placebo preparation to the
      contralateral side according to the randomization scheme. RESULTS: On the body
      side treated with the vitamin B(12) cream, the modified Six Area Six Sign Atopic
      Dermatitis score dropped to a significantly greater extent than on the placebo
      treated body side (for the investigational drug 55.34 +/- 5.74 SEM, for placebo
      28.87 +/- 4.86 SEM, P < 0.001). At the conclusion of the study, the investigator
      and patients awarded mostly a 'good' or 'very good' rating to the active drug
      (58% and 59%, respectively) and a 'moderate' or 'poor' rating to the placebo (89%
      and 87%, respectively). CONCLUSIONS: Topical vitamin B(12) is a new therapeutic
      approach in atopic dermatitis. These results document a significant superiority
      of vitamin B(12) cream in comparison with placebo with regard to the reduction of
      the extent and severity of atopic dermatitis. Furthermore, the treatment was very
      well tolerated and involved only very low safety risks for the patients.

PMID- 15149513
TI  - A new delivery system of clobetasol-17-propionate (lipid-loaded microspheres
      0.025%) compared with a conventional formulation (lipophilic ointment in a
      hydrophilic phase 0.025%) in topical treatment of atrophic/erosive oral lichen
      planus. A Phase IV, randomized, observer-blinded, parallel group clinical trial.
AB  - BACKGROUND: Topical application of clobetasol-17-propionate has been diffusely
      reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP),
      without exposing the patient to systemic side-effects. However, prolonged contact
      and respective topical effects on the oral mucosa should be avoided. OBJECTIVES:
      The aim of the present study was to evaluate efficacy and compliance of new lipid
      microspheres loaded with 0.025% of clobetasol propionate (formulation A) compared
      with a commonly used formulation (a sort of dispersion of a lipophilic ointment
      in a hydrophilic phase) with the same amount of drug (formulation B) in the
      topical treatment of OLP. PATIENTS AND METHODS: Fifty patients with symptomatic
      OLP were enrolled in a controlled single-blind phase IV clinical trial. After a
      dropout of five patients, a total of 45 patients [12 males and 33 females; mean
      age 61.1 years (+/- 12.3 SD; range 25-82)] were treated (17 with formulation A
      and 28 with formulation B, matched for gender and age; P > 0.2) with the same
      dosage regimen. At times T0, T1 and T2 we evaluated the following parameters: (i)
      pain score (by linear visual analogue scale; 0-100); (ii) clinical score; (iii)
      clinical resolution; and (iv) patient compliance. Statistical analysis was
      calculated using S-Plus 4.0 and SPSS 9.0 (Student's t-test, chi(2), Kolmogorov
      Smirnow, Friedman, Student-Newman-Keuls, Mann-Whitney U-test and Spearman tests).
      RESULTS: Both formulations were found to be similar for parameters ii, iii and
      iv, although with a better general trend for formulation A; a significant
      difference was registered for formulation A in terms of a reduction in painful
      symptoms (parameter i) at time T2 (P = 0.02). CONCLUSIONS: Our results suggest
      that the new topical drug delivery system (formulation A) may enhance, at least
      in terms of symptom remission and compliance, the effectiveness of clobetasol
      propionate at a dose of 0.025% in OLP therapy.

PMID- 15149514
TI  - Tobacco smoke is phototoxic.
AB  - BACKGROUND: Both cigarette smoke and ultraviolet (UV) radiation are known to
      cause changes of the skin which can be regarded as premature ageing. OBJECTIVES:
      To assess the theory that the effects of these two exposures could be linked by a
      phototoxic action of cigarette smoke. METHODS: A photohaemolysis test was used,
      in which human erythrocytes were incubated with cigarette smoke condensate,
      followed by UV irradiation and measurement of exposure-dependent haemolysis.
      RESULTS: Cigarette smoke condensate was clearly phototoxic. Photohaemolysis
      depended on the concentration of the condensate and UV dose and was more
      pronounced after exposure to UVA-rich than UVB-rich radiation. CONCLUSIONS:
      Phototoxicity may be a mechanism by which cigarette smoking causes premature skin
      ageing. An enhancing effect on photocarcinogenesis has also to be considered.

PMID- 15149515
TI  - Lymphocytopenia in lupus erythematosus: close in vivo association to
      autoantibodies targeting nuclear antigens.
AB  - BACKGROUND: Leukopenia and lymphopenia are typical features of lupus
      erythematosus (LE) and correlate with elevated disease activity and higher grades
      of systemic involvement. Antilymphocyte antibodies are regarded as the most
      likely rationale for the decreased cell numbers; however, their relevance has not
      been confirmed so far. OBJECTIVES: Previous investigations at our department have
      shown a significant correlation between diminished lymphocyte numbers and the
      presence of antinuclear antibodies (ANA). We wanted to achieve a better
      understanding of this phenomenon. METHODS: We performed a detailed analysis of
      autoantibodies and peripheral leucocyte subsets in 82 patients with different
      subtypes of LE. Leucocyte subsets were measured using flow cytometry (FACScan;
      Becton Dickinson, Franklin Lakes, NJ, USA.); autoantibodies were detected by
      indirect immunofluorescence and by enzyme-linked immunosorbent assay. RESULTS: A
      significant association (P < 0.05) between specific antibodies targeting nuclear
      antigens (SSA/Ro-52, SSB/La, snRNPs) and lymphocytopenia was found. CONCLUSIONS:
      We suppose that some of these autoantibodies might have an antilymphocyte effect.
      Apoptosis induction by specific antinuclear antibodies has already been described
      earlier, but to the best of our knowledge this is the first study presenting a
      strong indication of a possible interaction between these antibodies and
      lymphocyte subsets in vivo.

PMID- 15149516
TI  - Confirmation and refinement of a genetic locus for disseminated superficial
      actinic porokeratosis (DSAP1) at 12q23.2-24.1.
AB  - BACKGROUND: Our previous study has identified two loci for disseminated
      superficial actinic porokeratosis (DSAP), but the genes responsible are still
      unknown. OBJECTIVES: To narrow down the candidate regions and to assess candidate
      genes. METHODS: A genome-wide scan and linkage analysis were carried out in a
      newly collected five-generation Chinese family with DSAP. In addition, six
      candidate genes were screened for possible DSAP-associated mutations. RESULTS:
      DSAP in this family was associated with chromosome 12q. Fine mapping and
      haplotype construction refined the DSAP1 locus to a 4.4-cM interval. No disease
      associated mutation was detected in CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 or KIAA0789
      genes. CONCLUSIONS: The DSAP1 locus was localized to a 4.4-cM interval at
      chromosome 12q23.2-24.1. CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 and KIAA0789 genes
      were not associated with DSAP1.

PMID- 15149517
TI  - Autoimmune thyroid disease in anti-Ro/SS-A-positive children with annular
      erythema: report of two cases.
AB  - Anti-Ro/SS-A-associated recurrent annular erythema is a rare disorder, and
      represents a cutaneous manifestation of primary Sjogren's syndrome (SS). We
      report two childhood cases complicated with autoimmune thyroid disease, one with
      Graves' disease and the other with autoimmune thyroiditis. Both children were
      positive for anti-Ro/SS-A and anti-La/SS-B antibodies. One patient was lacking
      clinical SS with objective evidence of salivary gland involvement, while the
      other was diagnosed with primary SS. Our observation suggests that autoimmune
      thyroid disease in the subset of anti-Ro/SS-A-positive children with annular
      erythema might occur with similar frequency to that in adult primary SS.

PMID- 15149518
TI  - Treatment of recalcitrant pustular psoriasis with infliximab: effective reduction
      of chemokine expression.
AB  - Tumour necrosis factor (TNF)-alpha is thought to play a major role in the
      pathophysiology of psoriasis. Good clinical responses of psoriasis to anti-TNF
      alpha-based therapies have recently been demonstrated. We studied the effect of
      infliximab, a monoclonal antibody against TNF-alpha, on chemokine expression in
      pustular psoriasis. A 61-year-old man with a 2-year history of severe pustular
      psoriasis of von Zumbusch type who did not respond to conventional therapies
      responded rapidly to treatment with infliximab. The clinical response was
      reflected by an immediate and effective reduction of the neutrophil-attractant
      chemokines interleukin (IL)-8 and growth-related oncogene (Gro)-alpha as well as
      of monocyte chemoattractant protein (MCP)-1, as determined by mRNA in situ
      hybridization of lesional skin. No expression before or after treatment was seen
      for monokine induced by interferon (IFN)-gamma (MIG) and IFN-inducible protein
      (IP)-10. Thus, in pustular psoriasis the chemokine expression pattern is
      dominated by neutrophil-attractant chemokines and MCP-1 while, in contrast to
      plaque psoriasis, IFN-gamma-inducible lymphocyte-attractant chemokines such as IP
      10 and MIG are not abundant. We conclude that anti-TNF-alpha treatment with
      infliximab is an effective therapy in severe pustular psoriasis which is
      reflected by downregulation of disease-promoting chemokines such as IL-8, Gro
      alpha and MCP-1.

PMID- 15149519
TI  - Polyclonal expansion of T cells with the TCR V beta type of the tumour cell in
      lesions of cutaneous T-cell lymphoma: evidence for possible superantigen
      involvement.
AB  - The involvement of superantigens in the pathology of cutaneous T-cell lymphomas
      (CTCL) has been suggested before, but without unequivocal evidence for
      superantigen activity in the patients. Seeking evidence for superantigen activity
      we analysed clones and microdissected single cells isolated from the epidermis of
      early-stage lesions of a CTCL patient for their T-cell receptor (TCR) V beta
      expression and TCR V gamma gene rearrangements. The vast majority of these T
      cells expressed the TCR V beta family type of the tumour. From their TCR gamma
      gene rearrangements, however, these cells were polyclonal. The tumour cell clone
      accounted for about 60% of these cells, about 40% were of heterogeneous origin.
      This dominance of a single V beta family in the polyclonally expanded dermal T
      cell populations implies superantigen activity in the CTCL lesions.

PMID- 15149520
TI  - Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection
      of novel autoantigens and bronchial autoantibodies.
AB  - A 48-year-old woman with a follicular, grade III, B-cell non-Hodgkin lymphoma
      developed clinical, immunopathological and histological features of
      paraneoplastic pemphigus. The skin symptoms flared after repeated
      cyclophosphamide infusions, and were preceded and accompanied by a progressive
      dyspnoea. Although the skin and oral mucosal disease went into remission with
      high-dose steroid and intravenous immunoglobulin therapy, the severe alveolitis
      led to death. Immunoblotting of human epidermal extracts showed that the
      patient's serum IgG reacted with the 210-kDa envoplakin, 190-kDa periplakin, as
      well as the recombinant protein of BP180 NC16a domain. IgG and IgA enzyme-linked
      immunosorbent assays for desmoglein 3 were positive, too. Indirect
      immunofluorescence studies on COS-7 cells transiently transfected with
      desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA
      antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2. Serum IgG
      and IgA strongly stained rat bronchial epithelium, corresponding to
      autoantibodies possibly involved in the pathomechanism of the severe lung
      disease. In this case, which was characterized by a mixed IgA/IgG antibody panel
      displaying known and unique antigenicity, the serious episodes of paraneoplastic
      pemphigus flared after cyclophosphamide treatment.

PMID- 15149521
TI  - Pyoderma gangrenosum complicated by ecthyma gangrenosum.

PMID- 15149522
TI  - Beastly nodules instead of beauty: pseudoepitheliomatous hyperplasia developing
      after application of permanent make-up.

PMID- 15149523
TI  - Observations on angiopoietin 2 in patients with angiosarcoma.

PMID- 15149524
TI  - A case of familial cold autoinflammatory syndrome confirmed by the presence of a
      CIAS1 mutation.

PMID- 15149525
TI  - A third case of HOPP syndrome-confirmation of the phenotype.

PMID- 15149526
TI  - Successful treatment of pityriasis lichenoides with topical tacrolimus.

PMID- 15149527
TI  - A case of interstitial granulomatous drug reaction due to sennoside.

PMID- 15149528
TI  - Near-fatal anaphylaxis to patent blue V.

PMID- 15149529
TI  - Treatment of Epstein-Barr virus-associated peripheral T-cell lymphoma.

PMID- 15149530
TI  - Three-colour test in dermoscopy: a re-evaluation.

PMID- 15149531
TI  - Internet-based program for automatic discrimination of dermoscopic images between
      melanomas and Clark naevi.

PMID- 15149532
TI  - Successful treatment of disseminated granuloma annulare with topical tacrolimus.

PMID- 15149533
TI  - Does progressive symmetric erythrokeratoderma exist?

PMID- 15149534
TI  - Successful treatment of therapy-resistant metastatic Crohn's disease with
      infliximab.

PMID- 15149535
TI  - Eczema-like lesions and disruption of therapy in patients treated with interferon
      alfa and ribavirin for chronic hepatitis C: the value of an interdisciplinary
      assessment.

PMID- 15149537
TI  - Local molluscum contagiosum infection as a side-effect of pulsed-dye laser
      treatment.

PMID- 15149538
TI  - Subcutaneous calcification following high-dose radiotherapy.

PMID- 15149539
TI  - Presence of CD45RO+ CD34+ cells with collagen synthesis activity in nephrogenic
      fibrosing dermopathy: a new pathogenic hypothesis.

PMID- 15149540
TI  - Efficacy and systemic absorption of topical tacrolimus used in pyoderma
      gangrenosum.

PMID- 15149545
TI  - Lost in Translation: Obstacles to Translational Medicine.
AB  - When we launched the Journal of Translational Medicine a few months ago, we were
      interested primarily in exploring scientific consideration of this discipline.
      However, as editors of JTM, we have been contacted almost daily to discuss the
      problems faced by scientists and clinicians around the world who are challenging
      the traditional boundaries of science and medicine. Through these conversations,
      we have learned that translational medicine is in fact "lost in translation,"
      inspiring much angst, many promises and some Federal appropriations. However,
      little has been done to substantively promote this important field. Authoritative
      reviews on the subject are available to the interested reader 1234567. In this
      article, we will address JTM's "constituency" to report what we've learned about
      the obstacles to translational medicine from the myriad of phone conversations
      and e-mail interactions.

PMID- 15149544
TI  - PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human
      erythroid progenitors.
AB  - BACKGROUND: Erythropoietin is a multifunctional cytokine which regulates the
      number of erythrocytes circulating in mammalian blood. This is crucial in order
      to maintain an appropriate oxygen supply throughout the body. Stimulation of
      primary human erythroid progenitors (PEPs) with erythropoietin (Epo) leads to the
      activation of the mitogenic kinases (MEKs and Erks). How this is accomplished
      mechanistically remained unclear. RESULTS: Biochemical studies with human cord
      blood-derived PEPs now show that Ras and the class Ib enzyme of the
      phosphatidylinositol-3 kinase (PI3K) family, PI3K gamma, are activated in
      response to minimal Epo concentrations. Surprisingly, three structurally
      different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo.
      Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf
      kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced
      by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf
      inhibition and insensitive to PI3K and PKC inhibitors. CONCLUSIONS: These
      unexpected findings contrast with previous results in human primary cells using
      Epo at supraphysiological concentrations and open new doors to eventually
      understanding how low Epo concentrations mediate the moderate proliferation of
      erythroid progenitors under homeostatic blood oxygen levels. They indicate that
      the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo
      does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk.
      Instead, MEKs and Erks are signal mediators of PI3K, probably the recently
      described PI3K gamma, through a Raf-independent signaling pathway which requires
      PKC activity. It is likely that higher concentrations of Epo that are induced by
      hypoxia, for example, following blood loss, lead to additional mitogenic signals
      which greatly accelerate erythroid progenitor proliferation.

PMID- 15149546
TI  - Germline stem cells in the postnatal mammalian ovary: a phenomenon of prosimian
      primates and mice?

PMID- 15149547
TI  - Quality of life of 5-10 year breast cancer survivors diagnosed between age 40 and
      49.
AB  - BACKGROUND: The purpose of this report is to examine the correlates of quality of
      life (QOL) of a well-defined group of long-term breast cancer survivors diagnosed
      between the ages of 40 and 49. METHODS: Women were eligible if they were
      diagnosed with invasive breast cancer or ductal carcinoma in situ 5 to 10 years
      before June 30, 1998 and were enrolled at Group Health Cooperative, a health
      maintenance organization in western Washington State. A questionnaire was mailed
      to 290 women; 216 were included in this analysis. The questionnaire included
      standardized measures of QOL [e.g., the Cancer Rehabilitation Evaluation System
      (CARES-SF) and SF-36] as well as general demographic and medical information.
      ANOVA and logistic regression were used to estimate correlates of self-reported
      QOL. RESULTS: The mean age at diagnosis was 44.4 years, and the average time
      since diagnosis was 7.3 years. Women reported high levels of functioning across
      several standardized QOL scales; mild impairment was found on the CARES-SF Sexual
      Scale. The presence of breast-related symptoms at survey, use of adjuvant
      therapy, having lower income, and type of breast surgery were significantly
      associated with lower QOL 5 to 10 years post-diagnosis on one or more of the
      scales. CONCLUSIONS: Our results emphasize that younger long-term survivors of
      breast cancer have a high QOL across several standardized measures. However, the
      long-term consequences of adjuvant therapy and the management of long-term breast
      related symptoms are two areas that may be important for clinicians and women
      with breast cancer in understanding and optimizing long-term QOL.

PMID- 15149549
TI  - Optimization of ectopic gene expression in skeletal muscle through DNA transfer
      by electroporation.
AB  - BACKGROUND: Electroporation (EP) is a widely used non-viral gene transfer method.
      We have attempted to develop an exact protocol to maximize DNA expression while
      minimizing tissue damage following EP of skeletal muscle in vivo. Specifically,
      we investigated the effects of varying injection techniques, electrode surface
      geometry, and plasmid mediums. RESULTS: We found that as the amount of damage
      increased in skeletal muscle in response to EP, the level of beta-galactosidase
      (beta-gal) expression drastically decreased and that there was no evidence of
      beta-gal expression in damaged fibers. Two specific types of electrodes yielded
      the greatest amount of expression. We also discovered that DNA uptake in skeletal
      muscle following intra-arterial injection of DNA was significantly enhanced by
      EP. Finally, we found that DMSO and LipoFECTAMINE, common enhancers of DNA
      electroporation in vitro, had no positive effect on DNA electroporation in vivo.
      CONCLUSIONS: When injecting DNA intramuscularly, a flat plate electrode without
      any plasmid enhancers is the best method to achieve high levels of gene
      expression.

PMID- 15149548
TI  - Role of promoter hypermethylation in Cisplatin treatment response of male germ
      cell tumors.
AB  - BACKGROUND: Male germ cell tumor (GCT) is a highly curable malignancy, which
      exhibits exquisite sensitivity to cisplatin treatment. The genetic pathway(s)
      that determine the chemotherapy sensitivity in GCT remain largely unknown.
      RESULTS: We studied epigenetic changes in relation to cisplatin response by
      examining promoter hypermethylation in a cohort of resistant and sensitive GCTs.
      Here, we show that promoter hypermethylation of RASSF1A and HIC1 genes is
      associated with resistance. The promoter hypermethylation and/or the down
      regulated expression of MGMT is seen in the majority of tumors. We hypothesize
      that these epigenetic alterations affecting MGMT play a major role in the
      exquisite sensitivity to cisplatin, characteristic of GCTs. We also demonstrate
      that cisplatin treatment induce de novo promoter hypermethylation in vivo. In
      addition, we show that the acquired cisplatin resistance in vitro alters the
      expression of specific genes and the highly resistant cells fail to reactivate
      gene expression after treatment to demethylating and histone deacetylase
      inhibiting agents. CONCLUSIONS: Our findings suggest that promoter
      hypermethylation of RASSF1A and HIC1 genes play a role in resistance of GCT,
      while the transcriptional inactivation of MGMT by epigenetic alterations confer
      exquisite sensitivity to cisplatin. These results also implicate defects in
      epigenetic pathways that regulate gene transcription in cisplatin resistant GCT.

PMID- 15149551
TI  - Comparing breast cancer mortality rates before-and-after a change in availability
      of screening in different regions: extension of the paired availability design.
AB  - BACKGROUND: In recent years there has been increased interest in evaluating
      breast cancer screening using data from before-and-after studies in multiple
      geographic regions. One approach, not previously mentioned, is the paired
      availability design. The paired availability design was developed to evaluate the
      effect of medical interventions by comparing changes in outcomes before and after
      a change in the availability of an intervention in various locations. A simple
      potential outcomes model yields estimates of efficacy, the effect of receiving
      the intervention, as opposed to effectiveness, the effect of changing the
      availability of the intervention. By combining estimates of efficacy rather than
      effectiveness, the paired availability design avoids confounding due to different
      fractions of subjects receiving the interventions at different locations. The
      original formulation involved short-term outcomes; the challenge here is
      accommodating long-term outcomes. METHODS: The outcome is incident breast cancer
      deaths in a time period, which are breast cancer deaths that were diagnosed in
      the same time period. We considered the plausibility of the basic five
      assumptions of the paired availability design and propose a novel analysis to
      accommodate likely violations of the assumption of stable screening effects.
      RESULTS: We applied the paired availability design to data on breast cancer
      screening from six counties in Sweden. The estimated yearly change in incident
      breast cancer deaths per 100,000 persons ages 40-69 (in most counties) due to
      receipt of screening (among the relevant type of subject in the potential
      outcomes model) was -9 with 95% confidence interval (-14, -4) or (-14, -5),
      depending on the sensitivity analysis. CONCLUSION: In a realistic application,
      the extended paired availability design yielded reasonably precise confidence
      intervals for the effect of receiving screening on the rate of incident breast
      cancer death. Although the assumption of stable preferences may be questionable,
      its impact will be small if there is little screening in the first time period.
      However, estimates may be substantially confounded by improvements in systemic
      therapy over time. Therefore the results should be interpreted with care.

PMID- 15149550
TI  - Inter-observer agreement in the assessment of endoscopic findings in ulcerative
      colitis.
AB  - BACKGROUND: Endoscopic findings are essential in evaluating the disease activity
      in ulcerative colitis. The aim of this study was to evaluate how endoscopists
      assess individual endoscopic features of mucosal inflammation in ulcerative
      colitis, the inter-observer agreement, and the importance of the observers'
      experience. METHODS: Five video clips of ulcerative colitis were shown to a group
      of experienced and a group of inexperienced endoscopists. Both groups were asked
      to assess eight endoscopic features and the overall mucosal inflammation on a
      visual analogue scale. The following statistical analyses were used; Contingency
      tables analysis, kappa analysis, analysis of variance, Pearson linear correlation
      analysis, general linear models, and agreement analysis. All tests were carried
      out two-tailed, with a significance level of 5%. RESULTS: The inter-observer
      agreement ranged from very good to moderate in the experienced group and from
      very good to fair in the inexperienced group. There was a significantly better
      inter-observer agreement in the experienced group in the rating of 6 out of 9
      features (p < 0.05). The experienced and inexperienced endoscopists scored the
      "ulcerations" significantly different. (p = 0.05). The inter-observer variation
      of the mean score of "erosions", "ulcerations" and endoscopic activity index in
      mild disease, and the scoring of "erythema" and "oedema" in moderate-severe
      disease was significantly higher in the inexperienced group.A correlation was
      seen between all the observed endoscopic features in both groups of endoscopists.
      Among experienced endoscopists, a set of four endoscopic variables ("Vascular
      pattern", "Erosions", "Ulcerations" and Friability") explained 92% of the
      variation in EAI. By including "Granularity" in these set 91% of the variation in
      EAI was explained in the group of inexperienced endoscopists. CONCLUSION: The
      inter-observer agreement in the rating of endoscopic features characterising
      ulcerative colitis is satisfactory in both groups of endoscopists but
      significantly higher in the experienced group. The difference in the mean score
      between the two groups is only significant for "ulcerations". The endoscopic
      variables "Vascular pattern", "Erosions", "Ulcerations" and Friability" explained
      the overall endoscopic activity index. Even though the present result is quite
      satisfactory, there is a potential of improvement. Improved grading systems might
      contribute to improve the consistency of endoscopic descriptions.

PMID- 15149552
TI  - Development of microsatellite markers from an enriched genomic library for
      genetic analysis of melon (Cucumis melo L.).
AB  - BACKGROUND: Despite the great advances in genomic technology observed in several
      crop species, the availability of molecular tools such as microsatellite markers
      has been limited in melon (Cucumis melo L.) and cucurbit species. The development
      of microsatellite markers will have a major impact on genetic analysis and
      breeding of melon, especially on the generation of marker saturated genetic maps
      and implementation of marker assisted breeding programs. Genomic microsatellite
      enriched libraries can be an efficient alternative for marker development in such
      species. RESULTS: Seven hundred clones containing microsatellite sequences from a
      Tsp-AG/TC microsatellite enriched library were identified and one-hundred and
      forty-four primer pairs designed and synthesized. When 67 microsatellite markers
      were tested on a panel of melon and other cucurbit accessions, 65 revealed DNA
      polymorphisms among the melon accessions. For some cucurbit species, such as
      Cucumis sativus, up to 50% of the melon microsatellite markers could be readily
      used for DNA polymophism assessment, representing a significant reduction of
      marker development costs. A random sample of 25 microsatellite markers was
      extracted from the new microsatellite marker set and characterized on 40
      accessions of melon, generating an allelic frequency database for the species.
      The average expected heterozygosity was 0.52, varying from 0.45 to 0.70,
      indicating that a small set of selected markers should be sufficient to solve
      questions regarding genotype identity and variety protection. Genetic distances
      based on microsatellite polymorphism were congruent with data obtained from RAPD
      marker analysis. Mapping analysis was initiated with 55 newly developed markers
      and most primers showed segregation according to Mendelian expectations. Linkage
      analysis detected linkage between 56% of the markers, distributed in nine linkage
      groups. CONCLUSIONS: Genomic library microsatellite enrichment is an efficient
      procedure for marker development in melon. One-hundred and forty-four new markers
      were developed from Tsp-AG/TC genomic library. This is the first reported attempt
      of successfully using enriched library for microsatellite marker development in
      the species. A sample of the microsatellite markers tested proved efficient for
      genetic analysis of melon, including genetic distance estimates and identity
      tests. Linkage analysis indicated that the markers developed are dispersed
      throughout the genome and should be very useful for genetic analysis of melon.

PMID- 15149553
TI  - 15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species
      generation and mitochondrial membrane depolarization induced by oxidative stress.
AB  - BACKGROUND: With the use of cultured human retinal pigment epithelial cells, we
      have previously described a number of cellular responses to oxidative stress
      caused by H2O2. We also demonstrated that the cytotoxicity caused by H2O2 could
      be prevented by the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin
      J2 (15d-PGJ2). RESULTS: Further characterization of the experimental system
      indicated that the half-life of H2O2 in cultures was ~1 hour. At a fixed H2O2
      concentration, the cytotoxicity was dependent on the volume of H2O2 solution used
      in the culture, such that higher volume caused more cytotoxicity. Most cells were
      committed to die if the culture was treated for 2 hours with a cytotoxic
      concentration of H2O2. The prostaglandin derivative, 15d-PGJ2, could prevent
      oxidative damage caused by t-butyl hydroperoxide, in addition to H2O2. Further
      studies indicated that both H2O2 and tBH caused an increase in reactive oxygen
      species and depolarization of mitochondrial membrane potential. Pretreatment of
      cells with 1 microM 15d-PGJ2 led to a modest decrease in reactive oxygen species
      generation, and a significant restoration of mitochondrial membrane potential.
      CONCLUSION: This agent may be used in the future as a pharmacological tool for
      preventing cellular damage caused by oxidative stress.

PMID- 15149555
TI  - A fast algorithm for determining the best combination of local alignments to a
      query sequence.
AB  - BACKGROUND: Existing sequence alignment algorithms assume that similarities
      between DNA or amino acid sequences are linearly ordered. That is, stretches of
      similar nucleotides or amino acids are in the same order in both sequences.
      Recombination perturbs this order. An algorithm that can reconstruct sequence
      similarity despite rearrangement would be helpful for reconstructing the
      evolutionary history of recombined sequences. RESULTS: We propose a graph-based
      algorithm for combining multiple local alignments to a query sequence into the
      single combination of alignments that either covers the maximal portion of the
      query or results in the single highest alignment score to the query. This
      algorithm can help study the process of genome rearrangement, improve functional
      gene annotation, and reconstruct the evolutionary history of recombined proteins.
      The algorithm takes O(n2) time, where n is the number of local alignments
      considered. CONCLUSIONS: We discuss two example applications of the algorithm.
      The algorithm is able to provide useful reconstructions of the metazoan
      mitochondrial genome. It is also able to increase the percentage of a query
      sequence's amino acid residues for which similar stretches of amino acids can be
      found in sequence databases.

PMID- 15149557
TI  - An attempted suppression of liberty.
AB  - The Human Fertilisation and Embryology Authority (HFEA) report on gender
      selection is a presumptuous, biased, and misguided attempt to provide a basis on
      which to deny the freedom to make their own reproductive choices to citizens of
      Great Britain. The report should be soundly rejected.

PMID- 15149554
TI  - Multi-species sequence comparison reveals dynamic evolution of the elastin gene
      that has involved purifying selection and lineage-specific insertions/deletions.
AB  - BACKGROUND: The elastin gene (ELN) is implicated as a factor in both
      supravalvular aortic stenosis (SVAS) and Williams Beuren Syndrome (WBS), two
      diseases involving pronounced complications in mental or physical development.
      Although the complete spectrum of functional roles of the processed gene product
      remains to be established, these roles are inferred to be analogous in human and
      mouse. This view is supported by genomic sequence comparison, in which there are
      no large-scale differences in the ~1.8 Mb sequence block encompassing the common
      region deleted in WBS, with the exception of an overall reversed physical
      orientation between human and mouse. RESULTS: Conserved synteny around ELN does
      not translate to a high level of conservation in the gene itself. In fact, ELN
      orthologs in mammals show more sequence divergence than expected for a gene with
      a critical role in development. The pattern of divergence is non-conventional due
      to an unusually high ratio of gaps to substitutions. Specifically, multi-sequence
      alignments of eight mammalian sequences reveal numerous non-aligning regions
      caused by species-specific insertions and deletions, in spite of the fact that
      the vast majority of aligning sites appear to be conserved and undergoing
      purifying selection. CONCLUSIONS: The pattern of lineage-specific, in-frame
      insertions/deletions in the coding exons of ELN orthologous genes is unusual and
      has led to unique features of the gene in each lineage. These differences may
      indicate that the gene has a slightly different functional mechanism in mammalian
      lineages, or that the corresponding regions are functionally inert. Identified
      regions that undergo purifying selection reflect a functional importance
      associated with evolutionary pressure to retain those features.

PMID- 15149558
TI  - Carnitines and male infertility.
AB  - L-Carnitine (LC) and acetyl-L-carnitine (ALC) are highly concentrated in the
      epididymis and play a crucial role in sperm metabolism and maturation. They are
      related to sperm motility and have antioxidant properties. The objective of this
      review is to summarize the multiple roles played by LC and ALC in male
      reproduction, and to highlight their limitations as well as their benefits in the
      treatment of male infertility. A variety of studies support the conclusion that
      LC and/or ALC at total daily amounts of at least 3 g per day can significantly
      improve both sperm concentration and total sperm counts among men with astheno-
      or oligoasthenozoospermia. Although many clinical trials have demonstrated the
      beneficial effects of LC and ALC in selected cases of male infertility, the
      majority of these studies suffer from a lack of placebo-controlled, double blind
      design, making it difficult to reach a definite conclusion. Additional, well
      designed studies are necessary to further validate the use of carnitines in the
      treatment of patients with male infertility, specifically in men with poor semen
      quality.

PMID- 15149561
TI  - Chromatin condensation and DNA damage of human epididymal spermatozoa in
      obstructive azoospermia.
AB  - Obstructive azoospermia (OA) includes patients with different aetiologies of
      obstruction such as congenital bilateral absence of vas deferens (CBAVD), post
      vasectomy/failed vaso-vasostomy, or unknown (idiopathic). The frequency of DNA
      damaged spermatozoa and abnormal chromatin condensation in epididymal spermatozoa
      of OA patients was investigated for the different aetiology subgroups. DNA damage
      in caput epididymis spermatozoa was assessed with the TdT-UTP nick-end labelling
      (TUNEL) assay and chromatin condensation status was measured with chromomycin A3
      (CMA3) stain (n = 60 patients). All epididymal sperm samples showed high levels
      of TUNEL positivity (mean and SD, 43 +/- 17%). CMA3 rates showed large variation
      within the samples (mean and SD, 53 +/- 21%, range 7-97%); however, a significant
      difference in chromatin condensation was found between the different aetiologies
      of obstruction. The highest percentage of CMA3 positivity was found in the CBAVD
      and idiopathic groups (60 +/- 17 and 65 +/- 18% respectively) compared with the
      post-vasectomy samples (37 +/- 17%) or ejaculated spermatozoa from
      normozoospermic males (29 +/- 12%). In conclusion, despite the normal testicular
      histology in OA men, chromatin condensation differed between OA patients. The
      physiological heterogeneity found in chromatin condensation between patient
      subgroups is probably influenced by the aetiology of the obstruction.

PMID- 15149560
TI  - Induction of infertility in adult male bonnet monkeys by immunization with phage
      expressed peptides of the extracellular domain of FSH receptor.
AB  - Active immunization of proven fertile adult male bonnet monkeys (Macaca radiata)
      with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific
      peptides from the extracellular domain resulted in a progressive drop in sperm
      count with all animals becoming azoospermic by day 100. However, serum
      testosterone concentrations were unaltered during the entire course of study and
      animals exhibited normal mating behaviour. Breeding studies with proven fertile
      female monkeys revealed that all the immunized males were infertile. Following
      interruption of immunization on day 225, sperm counts returned to normal with
      restoration of fertility. These results indicate that infertility can be induced
      in adult male monkeys by interfering with the action of FSH using specific
      peptides of the extracellular domain of FSHR as antigens, without the risk of
      producing cross-reacting antibodies to the other glycoprotein hormones.

PMID- 15149562
TI  - Flow cytometry and microscopic acridine orange test: relationship with standard
      semen analysis.
AB  - Improved prediction of male fertility requires advances in semen analysis. This
      study examined the reproducibility and independence of the flow cytometry
      acridine orange test (FCM-AOT) of sperm chromatin integrity as an assessment of
      semen quality. The study found that FCM-AOT results are not significantly
      affected by up to 6 h delay in semen preparation (n = 9) or contamination of
      semen with moderate concentrations of bacteria (<10(8)/ml E. coli or Staph.
      epidermidis, n = 14). The variation of replicate measurements within samples was
      low (%Abnormal alpha(t): SD = 1.4, 95%CI = 4.6, n = 25) and different samples
      from the same men were mostly within the range of measurement error (n = 35). FCM
      AOT variables, in particular %Abnormal alpha(t), displayed significant
      correlations with motility (r = -0.557), vitality (r = -0.469) and morphology (r
      = -0.464, n = 201), which are similar in magnitude to those existing between the
      standard semen variables. Surprisingly, no correlation was found between
      %Abnormal alpha(t) and the microscopic acridine orange test (M-AOT) (n = 185),
      suggesting the FCM results are sensitive to a different aspect of sperm quality.
      In summary, this study confirms that although not totally independent of standard
      semen analysis or the M-AOT, it is found to be a robust, sensitive and
      reproducible measure of semen quality, representative of the individual.

PMID- 15149563
TI  - Outcome from consecutive assisted reproduction cycles in patients treated with
      recombinant follitropin alfa filled-by-bioassay and those treated with
      recombinant follitropin alfa filled-by-mass.
AB  - Recent advances in manufacturing procedures for r-hFSH have resulted in a
      preparation (follitropin alfa) that is highly consistent in both isoform profile
      and glycan species distribution. As a result, follitropin alfa can be reliably
      quantified and vials can be filled by mass. This study compared the clinical
      results in a well-established assisted reproduction programme during the
      crossover from standard follitropin alfa filled-by-bioassay (FSH-bio) to
      follitropin alfa filled-by-mass (FSH-mass). The study included the last 125
      patients treated with FSH-bio and the first 125 patients receiving FSH-mass for
      ovarian stimulation in their first assisted reproduction treatment cycle. Patient
      baseline characteristics were almost identical in the two groups. The duration of
      ovarian stimulation was significantly shorter in the FSH-mass group. The number
      of patients receiving the HCG injection and undergoing oocyte retrieval,
      follicular development and the serum concentration of oestradiol on the day of
      HCG injection were similar for the two treatment groups. The oocyte yield and the
      fertilization rates were similar in both groups of patients. However, embryo
      quality and implantation rates were significantly higher in the FSH-mass group.
      Accordingly, in spite of the mean number of embryos transferred being
      significantly lower in the FSH-mass group, there was a trend for higher clinical
      pregnancy rates in this group of patients. It is concluded that the new
      formulation of FSH-mass is more effective than the standard FSH-bio in terms of
      embryo quality, implantation rates, and number of days of stimulation.

PMID- 15149564
TI  - The Booroola (FecB) mutation is associated with smaller adrenal glands in young
      adult ewes.
AB  - The Booroola (FecB) phenotype is associated with a mutation in the bone
      morphogenetic protein (BMP) receptor 1B. The BMP action is important during
      development; surprisingly the only differences so far observed in adult animals
      are restricted to the ovaries where precocious development of the antral
      follicles and increased ovulation rate of mutant ewes is observed. The internal
      organs of 17 ewes homozygous for the mutation (BB) and 18 wild-type ewes (++)
      were macroscopically examined and weighed. No macroscopic differences were found,
      and the weight of the heart, liver, lungs, kidneys, and spleen were similar for
      both genotypes (P > 0.05). In contrast, the adrenals of BB ewes were lighter than
      those of ++ ewes (P < 0.05). The effect of the mutation on the adrenal function
      of cortisol secretion was measured at basal level and after an
      adrenocorticotrophic hormone challenge, before and after dexamethasone
      suppression. The Booroola mutation had no effect (P > 0.05) in any of these
      conditions. These findings indicate that the Booroola mutation also affects the
      size of the adrenal glands and suggest that the mutated gene could be important
      in the development of other organs in addition to the ovary. However, in the
      mutant ewes the function of the adrenal glands is not compromised or it is
      compensated.

PMID- 15149566
TI  - Assisted reproduction in the treatment of polycystic ovarian syndrome.
AB  - Treatment of patients with polycystic ovary syndrome (PCOS) with assisted
      reproductive techniques is a great challenge for the infertility specialist.
      Patients with PCOS demonstrate many problems, such as excessive body weight and
      hyperinsulinaemia, that render management more complex. Prior to treatment with
      IVF, the PCOS patient should be thoroughly evaluated for disclosure of
      endometrial neoplasia, hyperinsulinaemia, and other general health related
      problems. Ovarian stimulation for IVF carries the risks of overstimulation and
      severe hyperstimulation, which should be avoidable in most cases with preventive
      measures. The outcome in terms of pregnancy and implantation rates is similar for
      patients with PCOS when compared with patients undergoing IVF for other
      indications. There are some questions regarding oocyte and embryo quality in
      women with PCOS. This manifests itself in lower fertilization rate and decreased
      embryo quality in some studies. However, increased numbers of oocytes available
      for insemination or ICSI compensate for decreased fertilization rates and embryo
      quality. More recent studies suggest higher cumulative conception rates in women
      with PCOS when compared with controls. In-vitro maturation (IVM) of oocytes
      retrieved from non-stimulated or minimally stimulated cycles represents a viable
      option that should be considered seriously when assisted conception is attempted.
      Results of IVM, however, should be improved further and generalized before the
      technique can be advocated as the initial treatment approach in these patients.

PMID- 15149567
TI  - Role of changes in dietary habits in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous clinical condition. In most
      women, especially in the obese, all features of the metabolic syndrome,
      particularly insulin resistance and associated hyperinsulinaemia, are present.
      Insulin is a physiological hormone regulating ovarian function, specifically
      ovarian steroidogenesis and androgen blood transport and/or activity in the
      target tissues. Hyperinsulinaemia may therefore play a pivotal role in favouring
      the hyperandrogenic state and related clinical and metabolic alterations. The
      abdominal obesity phenotype is common, affecting more than half of PCOS women.
      Menstrual cycles and fertility rate are negatively affected by the presence of
      insulin resistance, hyperinsulinaemia and obesity. PCOS women with obesity and
      insulin resistance are the obvious target for lifestyle intervention, such as
      changes in dietary habits and increased physical activity. Weight loss should
      therefore represent the first-line approach in the treatment of obese PCOS women,
      since it significantly improves hormonal and metabolic abnormalities and may
      favour spontaneous ovulation and improve fertility rate in the majority of
      patients. Individualized pharmacological support aimed at favouring weight loss
      and maintenance and improving insulin resistance may play a complementary role to
      lifestyle intervention.

PMID- 15149568
TI  - Should insulin-sensitizing drugs be used in the treatment of polycystic ovary
      syndrome?
AB  - Insulin resistance is a central feature of polycystic ovary syndrome (PCOS).
      Hyperinsulinaemia contributes to anovulation, hyperandrogenism, infertility and
      early pregnancy loss in women with PCOS. Chronic hyperinsulinaemia also
      predisposes women with PCOS to increased risks of diabetes and cardiovascular
      events. Current data indicate that metformin, either as monotherapy or in
      combination with clomiphene in clomiphene-resistant patients, is an effective
      treatment for anovulation in PCOS. Initial evidence also suggests that insulin
      sensitizers may have a role in preventing early pregnancy loss. Of the available
      insulin-sensitizing agents, metformin has been the agent most frequently studied
      in PCOS, and has the least undesirable pregnancy safety profile. Ameliorating the
      metabolic syndrome associated with insulin resistance in PCOS with metformin may
      also prevent long-term cardiovascular and diabetes complications, pending further
      evidence. Based on these data, metformin should be a first-line therapy for women
      with PCOS.

PMID- 15149569
TI  - Orthotopic autotransplantation of cryopreserved ovarian tissue to a woman cured
      of cancer - follicular growth, steroid production and oocyte retrieval.
AB  - Cryopreservation of human ovarian tissue is now an option for cancer patients
      facing treatment with gonadotoxic regimes, as a means of preserving their
      fertility. So far, there have been only a few reports on autotransplantation of
      frozen-thawed tissue with regard to restoration of ovarian function. The present
      report describes a 32-year-old woman diagnosed with Hodgkin's lymphoma, who had
      cryopreserved ovarian tissue transplanted orthotopically after secondary ovarian
      failure due to chemotherapy. Only 8 weeks after transplantation, ultrasonography
      of the remaining ovary revealed two follicles with diameters of 10 and 15 mm.
      Concomitantly, circulating concentrations of oestradiol increased, while
      concentrations of gonadotrophins decreased. In the following months, the patient
      menstruated three times. Subsequent pituitary down-regulation with a
      gonadotrophin-releasing hormone (GnRH) agonist and ovarian stimulation resulted
      in development of one pre-ovulatory follicle from which a metaphase II oocyte was
      retrieved; however, this oocyte was unable to sustain further development after
      intracytoplasmic sperm injection (ICSI). Intrafollicular concentrations of
      oestradiol and progesterone suggested a normal luteinizing response of the
      follicle to human chorionic gonadotrophin stimulation. A 7-month follow-up
      revealed continued vivid follicular activity and normal oestradiol
      concentrations. In conclusion, cryopreserved human ovarian tissue restored
      ovarian function for several cycles and sustained development of mature oocytes
      in a woman cured of cancer.

PMID- 15149570
TI  - Occurrence of maternal and paternal spindles in unfertilized human oocytes:
      possible relationship to nucleation defects after silent fertilization.
AB  - Experience with conventional clinical IVF indicates that a first cleavage can
      occur in the absence of detectable pronuclear formation (so-called silent
      fertilization). In these instances, the first division is often asymmetrical and
      delayed when compared with normally fertilized siblings. In this study, DNA
      configurations and spindle organization were examined by fluorescence microscopy
      in metaphase II human oocytes that remained unfertilized after conventional IVF
      and were considered likely candidates for silent fertilization. The results show
      comparatively high frequencies of penetration in the absence of detectable
      pronuclear evolution, and that both a maternal meiotic and a sperm-derived
      mitotic-like spindle can coexist in the same oocyte. Patterns of cell division
      and blastomere nucleation in silent fertilizations suggest the possibility that
      this division may involve uniparental chromosomal segregation in which maternal
      and paternal DNA is differentially partitioned into daughter blastomeres. This
      pattern of inheritance may generate certain types of ploidy and nucleation
      defects detected at the 2- to 4-cell stage.

PMID- 15149572
TI  - Experimental results on the recognition of embryos in human assisted
      reproduction.
AB  - The recognition of embryos suitable for transfer in human assisted reproduction
      is important, and there is evidence that the morphology of the cells may
      influence the results achievable. A procedure for this recognition problem has
      been formulated based on morphological attributes of the images of the embryos,
      and it is therefore useful to compare the recognition of experts with that of a
      machine programme. The aim of this paper is to compare the precision in the
      recognition of viable embryos by a group of experts to that of a machine
      recognition procedure, both for a basic set of embryos and a blind set. Experts
      were asked to classify the images of 249 embryos transferred to 73 patients,
      indicated as the training set and another set of 103 embryos transferred to 35
      patients called the blind set. A machine programme was used for the same
      classification. For all the experts the results were statistically not
      significantly different from independence, which means that viable embryos are
      not recognized as such for both data sets. Instead, the machine algorithm
      recognizes in a statistically significant way, the membership class for the
      embryos submitted. Cell morphology is important for IVF, but differences do not
      appear to be discernable by the senses, clinical insight, experience and/or
      training, while classification by machine methods provides more accurate results,
      which could be improved by enlarging the training set.

PMID- 15149574
TI  - Preimplantation genetic diagnosis in patients with male meiotic abnormalities.
AB  - Indications and candidates for preimplantation genetic diagnosis (PGD) have
      increased in recent years. This study evaluates whether IVF-intracytoplasmic
      sperm injection (ICSI) results could be improved by selecting embryos through PGD
      AS (aneuploidy screening) in couples in whom the male partner presents meiotic
      abnormalities. Two hundred and fifty-six embryos were biopsied and 183 were
      suitable for analysis (73.2%). Ninety-two embryos showed normal chromosomal
      analysis (50.3% of the analysed embryos and 57.5% of the diagnosed embryos).
      Pregnancy, abortion and implantation rates were compared with 66 IVF-ICSI cycles
      performed in 44 patients with meiotic abnormalities without PGD (control group).
      No statistically significant differences in the pregnancy rate (52 versus 43.9%),
      implantation rate (32.1 versus 23.5%) and miscarriage rate (15.4 versus 10.3%)
      were observed between the groups. Although the embryos obtained from men with
      meiotic abnormalities showed a high frequency of chromosome abnormalities, no
      improvements in pregnancy and implantation rates were obtained after PGD-AS in
      the series analysed.

PMID- 15149576
TI  - Is MUC1 polymorphism associated with female infertility?
AB  - The transmembrane mucin glycoprotein (MUC1) has an anti-adhesive role, and
      functions to maintain a non-receptive uterine state. A polymorphic variation of
      the MUC1 gene has been associated with female infertility due to suspected
      failure of embryo implantation, based on the significant greater size of the
      lower allele observed in infertile women. The aim of this study was to confirm
      this preliminary observation using long polymerase chain reaction (PCR), which
      has amplified the 60-bp polymorphic variable number of tandem repeat (VNTR)
      associated to the binding domain of the MUC1 glycoprotein. DNA samples were
      obtained from 20 women, 10 fertile and 10 infertile, and the VNTR region was
      amplified through a long PCR procedure. The VNTR size range from 1.6 to 2.9 kb
      (22-44 motifs). The average size for the lower allele was 1.69 kb for both
      groups, and for the upper allele was 2.35 and 2.49 kb (P > 0.05) for fertile and
      infertile groups respectively. The VNTR polymorphism of the MUC1 gene was not
      associated with female infertility, although its significance cannot be
      discarded. It is suggested that other regulatory molecules and signals may
      interact with the MUC1 gene variations, favouring endometrial receptivity and
      embryo attachment.

PMID- 15149578
TI  - Newer Therapies for Inflammatory Bowel Disease.
AB  - Recent controlled and uncontrolled trial data in inflammatory bowel disease have
      suggested several new avenues of possible therapies and refined our understanding
      of the uses and selectiveness of anti-tumor necrosis factor (TNF)-based
      therapies. Infliximab remains the only proven effective anti-TNF therapy, whereas
      others have proven ineffective (etanercept, CDP-571) or of limited utility
      (thalidomide, CDP-870). A Crohn's disease Clinical trial Evaluating infliximab in
      a New long-term Treatment regimen (ACCENT I) and ACCENT II trials supported the
      strategy of using 5 to 10 mg/kg of infliximab on an every 8-week basis for
      maintenance of remission, although in clinical practice many physicians take
      variable approaches to maintenance of remission dosing schedules. On the other
      hand, no controlled trial data to date have supported the use of infliximab in
      ulcerative colitis. Therapies utilizing novel mechanistic approaches, such as
      hematopoietic growth factors, mitogen-activated protein (MAP)-kinase inhibition,
      and peroxisome proliferator activated receptor gamma ligand receptor binding have
      shown promise in small uncontrolled trials and await confirmation of their
      utility in randomized, placebo-controlled trials. Newer biologic (natalizumab) or
      cytokine-based therapies (monoclonal antibody to interleukin-6) have shown
      preliminary evidence of efficacy in controlled trials, but neither have yet been
      approved by the US Food and Drug Administration and, therefore, have not been
      commercialized. However, tacrolimus, a potent calcineurin inhibitor and inhibitor
      of interleukin-2 expression, has shown efficacy in Crohn's disease, albeit at the
      cost of substantial potential toxicity.

PMID- 15149580
TI  - Surgical Indications and Procedures in Ulcerative Colitis.
AB  - Chronic ulcerative colitis (CUC) is an inflammatory bowel disease limited to the
      mucosa of the rectum and colon. The inflammation begins in the rectum and
      progresses uninterrupted for variable distances. To date, no etiologic factor has
      been identified. However, population studies suggest there is both a genetic and
      environmental component contributing to the development of CUC. The natural
      history is one of a chronic inflammatory state, characterized by intermittent
      flares of disease activity. In a small number of patients, the initial
      presentation of CUC is of a fulminant nature. Medical therapy for the intestinal
      manifestations of CUC is directed at controlling symptoms through treatment of
      the underlying inflammatory process. Medical therapy is not curative for either
      the intestinal or extraintestinal manifestation of CUC. However, surgical removal
      of the colon and rectum cures the intestinal manifestations of the disease and
      eliminates or markedly reduces the associated risk of malignancy in longstanding
      CUC. The indications for surgical intervention are divided into two broad
      categories that influence the type of surgery performed: emergent and elective
      surgery. Emergency operations are directed at life-threatening complications of
      CUC and are not intended as definitive surgical treatment for CUC. Alternatively,
      elective surgery is intended as definitive treatment for the intestinal component
      of the disease. In appropriately selected patients, the best surgical treatment
      option is the total proctocolectomy with an ileal pouch-anal anastomosis (IPAA).
      The IPAA avoids the need for a permanent stoma and maintains the normal route of
      defecation. This is a technically demanding operation and should be performed by
      surgeons comfortable with the procedure. The severity and frequency of
      complications related to IPAA have decreased significantly since the introduction
      of the operations in the early 1980s. More importantly, long-term follow-up of
      IPAA patients has demonstrated that the functional results are durable and
      patient satisfaction remains high.

PMID- 15149579
TI  - Choosing Therapy on the Basis of Disease Classifications in Inflammatory Bowel
      Disease.
AB  - Crohn's disease and ulcerative colitis (UC) are heterogeneous disorders, and as
      such, the response to therapy is likewise heterogeneous. Therefore,
      stratification of patients into distinct phenotypes and potentially genotypes
      will lead to more definitive answers with respect to evaluation of novel and
      established therapies.

PMID- 15149582
TI  - Refractory Inflammatory Bowel Disease.
AB  - Therapeutic options for refractory colonic inflammation in patients with
      ulcerative colitis or Crohn's disease have recently been expanded with the
      introduction of biologic therapies. Intravenous corticosteroids and cyclosporine
      A remain the standard therapies for severe ulcerative colitis. Monoclonal
      antibodies directed at tumor necrosis factor-a have proven to be exceptionally
      efficacious in patients with severe or refractory Crohn's disease.
      Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has
      demonstrated efficacy for maintenance of remission in patients with refractory
      ulcerative colitis or Crohn's disease. The use of experimental biologic agents
      may be considered for those patients who fail to respond to or remain dependent
      on corticosteroids. Surgical intervention still remains for patients with severe
      colitis who fail to respond to medical therapy or develop life-threatening
      complications such as perforation or toxic megacolon.

PMID- 15149581
TI  - Nutritional Therapy in Inflammatory Bowel Disease.
AB  - Nutritional intervention is an important adjunctive therapy for patients with
      inflammatory bowel disease (IBD). The correction and maintenance of nutritional
      status, achieved by careful nutritional monitoring and intervention, should be an
      integral part of the multidisciplinary management of IBD throughout all stages of
      the disease. In acute Crohn's disease, enteral nutrition (polymeric and
      elemental) is an effective and safe primary therapy for many patients. Enteral
      diets should be considered as primary therapy in pediatric Crohn's disease
      patients, especially in children with poor nutritional status or growth
      impairment and in patients with severe drug-induced side effects. Total
      parenteral nutrition does not have a primary therapeutic role in IBD.

PMID- 15149583
TI  - Treatment of Hereditary Colorectal Cancer Syndromes.
AB  - Colorectal cancer is the second leading cause of cancer-related death in the
      United States. Although most colorectal cancers are sporadic, about 25% have a
      familial predisposition and 5% to 7% are hereditary and occur in genetically
      distinct high-risk families. Advances in treatment options and management of
      hereditary colorectal cancer syndromes that have occurred over the past years
      have been principally due to advances in the understanding of the genetics of
      these syndromes and in additional options for testing. This has led to the
      possibility of preclinical diagnosis and early surveillance and treatment. In
      addition, improvements in medical and surgical management have also occurred.
      This article focuses on four hereditary colon cancer syndromes: familial
      adenomatous polyposis, hereditary non-polyposis colorectal cancer, juvenile
      polyposis syndrome, and Peutz-Jeghers syndrome.

PMID- 15149584
TI  - Treatment Options for Primary Constipation.
AB  - Patients suffering from primary constipation often show symptom improvement with
      increased intake of fiber. Bulk laxatives are a core component of treatment if
      dietary fiber is unsuccessful in alleviating symptoms. Although there are a
      number of commercial laxative preparations available, only polyethylene glycol
      (PEG), an osmotic laxative, should be used on a daily basis. For the elderly,
      saline laxatives may be used on a regular basis, provided there are no cardiac or
      renal comorbid contraindications. Tegaserod, a 5-HT(4) partial receptor agonist,
      is approved for the treatment of constipation in female patients. The appropriate
      role of biofeedback remains to be determined. Surgery should be reserved for
      patients with slow transit constipation refractory to medical therapy. Patients
      being considered for surgery should be evaluated at institutions with substantial
      expertise in the investigation and management of this population.

PMID- 15149585
TI  - Treatment of Clostridium difficile Infection.
AB  - With the introduction of broad-spectrum antibiotics into clinical practice,
      Clostridium difficile infection has become the most common cause of infectious
      diarrhea in hospitalized patients. Although mild cases may resolve by
      discontinuing antibiotics, thus allowing re-establishment of colonic microflora,
      oral metronidazole or vancomycin is indicated if the process is more severe.
      Metronidazole may be given intravenously, with intracolonic therapeutic levels
      achieved by excretion of drug into bile and exudation across inflamed tissue.
      Vancomycin is preferred treatment of severe cases. Bacitracin given orally is a
      therapeutic alternative and cholestyramine is a useful adjunct. Most patients
      with diarrhea or colitis caused by C. difficile respond to initial therapy;
      however, up to 20% experience relapse when treatment is discontinued. Repeating
      initial therapy for 10 to 14 days is indicated for first relapse. Multiple
      relapses require prolonged treatment with vancomycin, which may be supplemented
      with cholestyramine. Saccharomyces boulardii alone or in combination with
      vancomycin has been reported to be an effective therapeutic alternative for
      recurrent infection. Intravenous immunoglobulin can be effective in patients with
      severe recurrent Clostridium difficile colitis and immune deficiency or low
      pretreatment levels of serum antitoxin. Surgery is indicated only if recurrent
      infections are severe and associated with serious complications.

PMID- 15149586
TI  - Endoscopic Management of Lower Gastrointestinal Bleeding.
AB  - Colonoscopy continues to be the primary tool for diagnostic evaluation and
      management of lower gastrointestinal bleeding (LGIB). With the advent of newer
      endoscopy delivery therapeutic modalities, the treatment of LGIB has changed
      dramatically over the decades. The most dramatic change has been the role of
      surgery, which has been substantially reduced due to the therapeutic colonoscopy.
      This article reviews recent advances in the endoscopic treatment options in LGIB
      of the colon and rectum.

PMID- 15149587
TI  - Mise en place-this bud's for the Golgi.
AB  - Selective cargo export from the endoplasmic reticulum is brought about by the
      budding of COPII vesicles. While the main structural components of the COPII coat
      have been identified and characterized, the regulatory event(s) promoting COPII
      vesicle biogenesis and cargo selection still remains largely unknown. New data by
      Glick and colleagues suggest that Sec12 and COPII function may be downstream of
      important early events coordinated by transitional ER (tER) exit sites.

PMID- 15149588
TI  - Control of DNA synthesis and mitosis by the Skp2-p27-Cdk1/2 axis.
AB  - A new study reveals a novel role for p27 in inhibiting Cdk1 activity at G2/M and
      shows that p27 deficiency almost completely rescues the aberrations observed in
      Skp2(-/-) mice, demonstrating that p27 is the principal downstream effector of
      the SCF(Skp2) ubiquitin ligase.

PMID- 15149589
TI  - FoxO: linking new signaling pathways.
AB  - Two recent reports reveal new roles for FoxO proteins in cell proliferation and
      tumorigenesis. Seoane and colleagues show that FoxO proteins play key roles in
      the TGFbeta-dependent activation of p21Cip1 by partnering with Smad3 and Smad4.
      FoxG1, a protein from a distinct Fox subfamily, binds FoxO/Smad complexes and
      blocks p21Cip1 expression. These interactions establish a relationship between
      the PI3K pathway, FoxG1, and the TGFbeta/Smad pathways. The second report
      identifies IkappaB kinase as a negative regulator of FoxO proteins, suggesting a
      mechanism for relieving negative regulation of cell cycle and promoting tumor
      cell proliferation.

PMID- 15149592
TI  - GroEL mediates protein folding with a two successive timer mechanism.
AB  - GroEL encapsulates nonnative substrate proteins in a central cavity capped by
      GroES, providing a safe folding cage. Conventional models assume that a single
      timer lasting approximately 8 s governs the ATP hydrolysis-driven GroEL
      chaperonin cycle. We examine single molecule imaging of GFP folding within the
      cavity, binding release dynamics of GroEL-GroES, ensemble measurements of
      GroEL/substrate FRET, and the initial kinetics of GroEL ATPase activity. We
      conclude that the cycle consists of two successive timers of approximately 3 s
      and approximately 5 s duration. During the first timer, GroEL is bound to ATP,
      substrate protein, and GroES. When the first timer ends, the substrate protein is
      released into the central cavity and folding begins. ATP hydrolysis and phosphate
      release immediately follow this transition. ADP, GroES, and substrate depart
      GroEL after the second timer is complete. This mechanism explains how GroES
      binding to a GroEL-substrate complex encapsulates the substrate rather than
      allowing it to escape into solution.

PMID- 15149591
TI  - Telomeres are double-strand DNA breaks hidden from DNA damage responses.
AB  - A network of ATM/ATR-mediated events regulates cell cycle checkpoints and genomic
      integrity and contributes to the processing of DNA double-strand breaks in both
      genomic DNA and at telomeres. In yeast and in human cells, investigators,
      including, and Herbig et al., published in this issue of Molecular Cell, are
      beginning to decipher the signaling pathways involved at the telomeres.

PMID- 15149590
TI  - Stay close to your sister.
AB  - Yeast Sir2 protein regulates chromatin structure and suppresses recombination at
      the multiple tandem rDNA array. In the current issue of Cell, Kobayashi and
      colleagues reinvestigate rDNA dynamics in sir2 strains and find that Sir2 is
      necessary to recruit cohesins to the array, which influences the nature of rDNA
      recombination events.

PMID- 15149593
TI  - Endonuclease-mediated mRNA decay involves the selective targeting of PMR1 to
      polyribosome-bound substrate mRNA.
AB  - PMR1 is a polysome-associated mRNA endonuclease that initiates the
      destabilization of albumin mRNA. The current study examined whether endonuclease
      mediated mRNA decay involved the selective binding of PMR1 to substrate mRNA on
      polysomes. PMR1 is uniformly distributed throughout the cytoplasm on polysomes
      and in lighter complexes and does not colocalize in cytoplasmic foci with Dcp1.
      Deletion mutagenesis identified polysome-targeting domains in the N and C termini
      of PMR1, either of which could target GFP to polysomes. Selectivity in targeting
      to polysome-bound substrate mRNP was determined by testing the ability of full
      length PMR1 or protein lacking targeting domains to recover albumin and
      luciferase mRNA from dissociated polysomes. Only PMR1 bearing intact polysome
      targeting domains selectively recovered albumin mRNA, and polysome targeting of
      both protein and substrate was required for the efficient degradation of albumin
      mRNA. Thus, endonuclease-mediated mRNA decay occurs on a polysome-bound complex
      containing PMR1 and its substrate mRNA.

PMID- 15149594
TI  - The Paf1 complex has functions independent of actively transcribing RNA
      polymerase II.
AB  - The yeast Paf1 complex, minimally composed of Paf1, Ctr9, Cdc73, Rtf1, and Leo1,
      was originally isolated in association with RNA polymerase II (Pol II). Paf1
      complex components are abundant and colocalize with Pol II on chromatin at
      promoters and in the coding regions of actively transcribed genes. Loss of Paf1
      results in severe phenotypes and reduced amounts of other Paf1 factors, with
      little effect on abundance or chromatin distribution of Pol II, proteins
      important for transcriptional elongation (Spt5, Spt16), or RNA processing (Sub2).
      Loss of Paf1 factors causes a reduction of Pol II Ser2 phosphorylation and
      shortened poly(A) tails, suggesting that the complex facilitates linkage of
      transcriptional and posttranscriptional events. Surprisingly, loss of Rtf1 or
      Cdc73, with little phenotypic consequence, results in loss of Paf1 factors from
      chromatin and a significant reduction in Paf1/Pol II association. Therefore, the
      major functions of Paf1 can be independent of actively transcribing Pol II.

PMID- 15149595
TI  - Elongator interactions with nascent mRNA revealed by RNA immunoprecipitation.
AB  - The histone acetyltransferase Elongator was originally isolated as a component of
      the elongating form of RNA polymerase II (RNAPII) and a plethora of data has
      since supported a role for the factor in transcription. However, recent data has
      suggested that it is predominantly cytoplasmic and does not associate with the
      DNA of transcribed genes in vivo. Here, we report that Elongator binds to RNA
      both in vitro and in vivo. Using a modified chromatin immunoprecipitation
      procedure, RNA immunoprecipitation (RIP), we show that Elongator is indeed
      present at several actively transcribed genes and that it associates with the
      nascent RNA emanating from elongating RNAPII along the entire coding region of a
      gene. These results strongly support a role for Elongator in transcript
      elongation.

PMID- 15149596
TI  - Pbx marks genes for activation by MyoD indicating a role for a homeodomain
      protein in establishing myogenic potential.
AB  - Skeletal muscle differentiation is initiated by the transcription factor MyoD,
      which binds directly to the regulatory regions of genes expressed during skeletal
      muscle differentiation and initiates chromatin remodeling at specific promoters.
      It is not known, however, how MyoD initially recognizes its binding site in a
      chromatin context. Here we show that the H/C and helix III domains, two domains
      of MyoD that are necessary for the initiation of chromatin remodeling at the
      myogenin locus, together regulate a restricted subset of genes, including
      myogenin. These domains are necessary for the stable binding of MyoD to the
      myogenin promoter through an interaction with an adjacent protein complex
      containing the homeodomain protein Pbx, which appears to be constitutively bound
      at this site. This demonstrates a specific mechanism of targeting MyoD to loci in
      inactive chromatin and reveals a critical role of homeodomain proteins in marking
      specific genes for activation in the muscle lineage.

PMID- 15149597
TI  - Cellular stress alters the transcriptional properties of promoter-bound Mot1-TBP
      complexes.
AB  - Mot1 associates with transcriptionally active promoters, and it directly affects
      transcriptional activity in a positive or negative manner, depending on the gene.
      As determined by sequential chromatin immunoprecipitation, Mot1 co-occupies
      promoters with TBP, but not with TFIIB, TFIIA, or Pol II when cells are grown in
      normal conditions. This strongly suggests that the Mot1-TBP complex is
      transcriptionally inactive, and hence is in dynamic equilibrium with
      transcriptionally active forms of TBP. Surprisingly, in response to heat shock
      and other forms of environmental stress, Mot1 co-occupies promoters with TFIIB
      and elongation-competent Pol II, but not with TFIIA. This suggests that
      functional preinitiation complexes can contain Mot1 instead of TFIIA in vivo.
      Thus, Mot1-TBP complexes can exist in active and inactive forms that are
      regulated by environmental stress.

PMID- 15149598
TI  - Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible
      mechanism for the polymerase switch in response to DNA damage.
AB  - Most types of DNA damage block replication fork progression during DNA synthesis
      because replicative DNA polymerases are unable to accommodate altered DNA bases
      in their active sites. To overcome this block, eukaryotic cells employ
      specialized translesion synthesis (TLS) polymerases, which can insert nucleotides
      opposite damaged bases. In particular, TLS by DNA polymerase eta (poleta) is the
      major pathway for bypassing UV photoproducts. How the cell switches from
      replicative to TLS polymerase at the site of blocked forks is unknown. We show
      that, in human cells, PCNA becomes monoubiquitinated following UV irradiation of
      the cells and that this is dependent on the hRad18 protein. Monoubiquitinated
      PCNA but not unmodified PCNA specifically interacts with poleta, and we have
      identified two motifs in poleta that are involved in this interaction. Our
      findings provide an attractive mechanism by which monoubiquitination of PCNA
      might mediate the polymerase switch.

PMID- 15149600
TI  - Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1
      with telomeres in vivo.
AB  - The phosphoinositide (PI)-3-kinase-related kinase (PIKK) family proteins Tel1p
      and Mec1p have been implicated in the telomere integrity of Saccharomyces
      cerevisiae. However, the mechanism of PIKK-mediated telomere length control
      remains unclear. Here, we show that Tel1p and Mec1p are recruited to the
      telomeres at specific times in the cell cycle in a mutually exclusive manner. In
      particular, Mec1p interacts with the telomeres during late S phase and is
      associated preferentially with shortened telomeres. We propose a model in which
      telomere integrity is maintained by the reciprocal association of PIKKs, and
      Mec1p acts as a sensor for structural abnormalities in the telomeres. Our study
      suggests a mechanistic similarity between telomere length regulation and DNA
      double-strand break repair, both of which are achieved by the direct association
      of PIKKs.

PMID- 15149599
TI  - Telomere shortening triggers senescence of human cells through a pathway
      involving ATM, p53, and p21(CIP1), but not p16(INK4a).
AB  - Cellular senescence can be triggered by telomere shortening as well as a variety
      of stresses and signaling imbalances. We used multiparameter single-cell
      detection methods to investigate upstream signaling pathways and ensuing cell
      cycle checkpoint responses in human fibroblasts. Telomeric foci containing
      multiple DNA damage response factors were assembled in a subset of senescent
      cells and signaled through ATM to p53, upregulating p21 and causing G1 phase
      arrest. Inhibition of ATM expression or activity resulted in cell cycle reentry,
      indicating that stable arrest requires continuous signaling. ATR kinase appears
      to play a minor role in normal cells but in the absence of ATM elicited a delayed
      G2 phase arrest. These pathways do not affect expression of p16, which was
      upregulated in a telomere- and DNA damage-independent manner in a subset of
      cells. Distinct senescence programs can thus progress in parallel, resulting in
      mosaic cultures as well as individual cells responding to multiple signals.

PMID- 15149601
TI  - During apoptosis bcl-2 changes membrane topology at both the endoplasmic
      reticulum and mitochondria.
AB  - In healthy cells the antiapoptotic protein Bcl-2 adopts a topology typical of
      tail-anchored proteins with only the hydrophobic carboxyl terminus inserted into
      the membrane, as shown by labeling cell lysates with a membrane-impermeant
      sulfhydryl-specific reagent. Induction of apoptosis in cells triggered a change
      in the conformation of Bcl-2 such that cysteine 158 near the base of helix 5
      inserted into the lipid bilayer of both endoplasmic reticulum and mitochondria
      where it was protected from labeling. Addition of a peptide corresponding to the
      BH3 domain of the proapoptotic protein Bim to cell lysates triggered a similar
      conformational change in Bcl-2, demonstrating that preexisting, membrane-bound
      Bcl-2 proteins change topology.

PMID- 15149602
TI  - Structural mechanism for inactivation and activation of CAD/DFF40 in the
      apoptotic pathway.
AB  - CAD/DFF40 is responsible for the degradation of chromosomal DNA into nucleosomal
      fragments and subsequent chromatin condensation during apoptosis. It exists as an
      inactive complex with its inhibitor ICAD/DFF45 in proliferating cells but becomes
      activated upon cleavage of ICAD/DFF45 into three domains by caspases in dying
      cells. The molecular mechanism underlying the control and activation of CAD/DFF40
      was unknown. Here, the crystal structure of activated CAD/DFF40 reveals that it
      is a pair of molecular scissors with a deep active-site crevice that appears
      ideal for distinguishing internucleosomal DNA from nucleosomal DNA. Ensuing
      studies show that ICAD/DFF45 sequesters the nonfunctional CAD/DFF40 monomer and
      is also able to disassemble the functional CAD/DFF40 dimer. This capacity
      requires the involvement of the middle domain of ICAD/DFF45, which by itself
      cannot remain bound to CAD/DFF40 due to low binding affinity for the enzyme.
      Thus, the consequence of the caspase-cleavage of ICAD/DFF45 is a self-assembly of
      CAD/DFF40 into the active dimer.

PMID- 15149604
TI  - Measurement of hepatic phenylalanine metabolism in children using the [(13)C]
      phenylalanine breath test and gas chromatography-mass spectrometry.
AB  - The essential amino acid, phenylalanine (PA), is known to be metabolized mainly
      in the liver of human adults. Because the liver is still in the developmental
      phase, the PA-related metabolic events in infants remain unsolved. In this study,
      evaluations of development in hepatic PA metabolism in 37 children and 16 adults
      were attempted using the (13)C -PA breath test (PBT). The subjects were
      categorized into four groups according to their ages in years and months: 2 years
      and 0 month to 3 years and 5 months (group I; n = 12); 3 years and 6 months to 4
      years and 11 months (group II, n = 12); 5 years and 0 month to 6 years and 11
      months (group III, n = 13); and healthy adults (group IV; n = 16). Changes in
      CO(2) level of exhaled gas at various time intervals after oral administration of
      (13)C -PA were monitored using gas chromatography-mass spectrometry to derive the
      (13)C excretion rate, cumulative excretion curve and time maximum [(13)C
      excretion rate (T(MAX)). In the present investigation involving children,
      significant increases of maximum(13)C excretion rate and cumulative excretion at
      120 min after administration were established in group III. Furthermore,
      differences in PBT were not established between groups III and IV. The index for
      first-pass effect, T(MAX), did not change with time. From the above findings, the
      (13)C excretion rate increased with time although hepatic PA metabolism in
      infants remained underdeveloped, and children at the age of 5-7 years manifested
      PA metabolism similar to that of adults.

PMID- 15149606
TI  - Quantification of urinary 5-aminolevulinic acid by gas chromatography-mass
      spectrometry.
AB  - In this report, we describe a method for the specific quantification of urinary 5
      aminolevulinic acid. It is based on gas chromatographic mass spectrometric
      measurement of the trimethylsilyl ester of the ethylacetoacetate pyrrole
      derivative of 5-aminolevulinic acid. Selected ion monitoring (SIM) was used for
      quantification using 3-hydroxymyristic acid as an internal standard. The
      detection limit of this method was 0.1 nmol/ml. This method was applied to the
      determination of urinary 5-aminolevulinic acid from a tyrosinemia type I patient
      and normal subjects, and 21.4 mmol/mol creatinine and 0.54+/- 0.49 mmol/mol
      creatinine (n = 7), respectively, were detected. Less than 0.2 ml urine was
      sufficient for the determination of 5-aminolevulinic acid in healthy subjects.

PMID- 15149605
TI  - Enantioselective immunorecognition of protein modification with optically active
      ibuprofen using polyclonal antibody.
AB  - Formation of covalently bound protein adducts with 2-arylpropionic acids (2-APAs)
      has been proposed as a possible explanation for hypersensitivity and toxic
      responses to chiral carboxylic acid drugs. To identify the cellular proteins
      chemically modified with optically active (S)-ibuprofen, we generate polyclonal
      antibodies by immunizing rabbits with immunogen coupled to bovine serum albumin
      (BSA) via the spacer of 4-aminobutyric acid. The resulting antibodies largely
      cross-reacted with N-alpha-(t-butoxycarbonyl)--(S)-ibuprofenyl lysine as well as
      with the conjuguated (S)-ibuprofen with glycine and taurine and unconjugated (S)
      ibuprofen, enabling enantioselective detection of (S)-ibuprofen residues anchored
      on ovalbumin molecules, introduced by the reaction of the ibuprofen p-nitrophenyl
      ester. Furthermore, immunoblotting with an antibody allows the enantioselective
      detection of (S)-ibuprofen-introduced glutathione-S-transferase (GST). These
      results indicate that the developed method will be useful for monitoring the
      generation and localization of protein covalently bound with (S)-ibuprofen, which
      may be the cause of ibuprofen-induced toxicity.

PMID- 15149607
TI  - Development of an isotope dilution mass spectrometry assay for HbA1c based on
      enzyme-cleaved peptide analysis.
AB  - HbA1c is an index of control in diabetes patients. We report a highly
      reproducible measurement method for HbA1c based on analysis of the enzyme-cleaved
      peptide by electrospray ionization mass spectrometry using deuterium-labeled
      synthetic peptides as internal standards. Intra- and inter-assay coefficients of
      variation for the novel method ranged from 1.23 to 1.99% for samples with high
      and low HbA1c. Using this method, we clarified the extent of discrepancies among
      the indices of diabetes measured by conventional methods and the ESI method for
      clinical samples including those from patients with Hb variants. High-performance
      liquid chromatography (HPLC) methods for most samples with variants underestimate
      the true HbA1c value, although a few variants give a positive error for HbA1c.
      Immunoassays may also underestimate the values, if the reactivity of the antibody
      is low against the glycated N-terminal of the variant beta-chains by
      conformational change. The method proposed here is an important step to establish
      a candidate definitive method, and is also useful in assessing specific HbA1c
      test systems using samples containing Hb variants.

PMID- 15149608
TI  - Rapid and sensitive screening for and chemical diagnosis of Canavan disease by
      gas chromatography-mass spectrometry.
AB  - The use of a rapid and sensitive assay for N-acetylaspartate (NAA) in urine or
      eluates from dried urine on filter paper to make a chemical diagnosis of Canavan
      disease (CD) is described. It involves a simplified urease pretreatment for
      sample preparation and gas chromatography-mass spectrometry (EI, scanning mode)
      with or without stable isotope dilution. Significant improvements in the recovery
      of NAA and the GC-MS data-handling device made the assay without stable isotope
      dilution sensitive and quantitative enough to diagnose CD: Its coefficient of
      variation (CV) was below 12%. The CV obtained with stable isotope dilution was
      below 9%. One patient with CD had an abnormal NAA level that was more than 6 S.D.
      above the mean of the age-matched controls. This diagnostic procedure is accurate
      for screening and for the chemical diagnosis of CD, with a good cost:benefit
      ratio. The urinary NAA levels of the healthy controls decreased significantly
      with age. This change should be considered in making a chemical diagnosis of this
      disease.

PMID- 15149609
TI  - Determination of phosphatidylcholine monohydroperoxides using quadrupole time-of
      flight mass spectrometry.
AB  - An improved technique for the analysis of phosphatidylcholine (PC)
      monohydroperoxides was developed using quadrupole time-of-flight (Q-TOF) mass
      spectrometry with electrospray ionization. Separation was obtained using an HPLC
      C8 column with a gradient of methanol and 10 mM aqueous ammonium acetate.
      Monohydroperoxides of palmitoyl-linoleoyl (C16:0/C18:2) PC, stearoyl-linoleoyl
      (C18:0/C18:2) PC, and oleoyl-linoleoyl (C18:1/C18:2) PC were detected mainly as
      MH(+) and [M+Na](+) ions in the heart of the intact rat. Using standard synthetic
      PCOOH (C16:0/C18:2-OOH), the lipid extract component was identified as
      (C16:0/C18:2-OOH) PC based on the product ions of ESI-MS-MS and, the PCOOH
      concentration was quantitated using HPLC with chemiluminescence detection. Two
      epoxyhydroxy derivatives of the three PCs mentioned above were also detected.
      This is the first report to show the presence of monohydroperoxides and
      epoxyhydroxy-derivatives of (C16:0/C18:2)PC, (C18:0/C18:2)PC, and (C18:1/C18:2)
      PC in the rat heart.

PMID- 15149610
TI  - Evaluation of sphingolipids in vitreous bodies from a patient with Gaucher
      disease, using delayed extraction matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry.
AB  - Gaucher disease is a glycolipid storage disorder characterized by the
      accumulation of glucosylceramide in tissues. Using delayed extraction matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI
      TOF-MS), we analyzed sphingolipids in vitreous bodies from a patient with Gaucher
      disease who suffered from vitreous opacities. Crude lipids were extracted from
      the freeze-dried vitreous bodies with chloroform and methanol. After mild
      alkaline treatment of the crude lipids, a sphingolipid fraction was prepared and
      analyzed by DE MALDI-TOF-MS. The results were as follows: (a). the m/z values of
      the ions found in the mass spectra for both the control and the Gaucher disease
      patient corresponded to different sphingomyelin species. (b). The mass spectrum
      of the Gaucher disease patient showed additional ions with m/z values
      corresponding to different ceramide monohexoside (CMH) species. It was indicated
      that the accumulation of CMH in vitreous bodies from Gaucher disease patients
      could be easily detected with the DE MALDI-TOF-MS method.

PMID- 15149611
TI  - Application of liquid chromatography-tandem mass spectrometry for the
      determination of opioidmimetics in the brain dialysates from rats treated with
      opioidmimetics intraperitoneally.
AB  - We have determined three opioidmimetics (compounds I-III) in the rat brain
      dialysates after intraperitoneal (i.p.) administration of compounds I-III using a
      liquid chromatography/mass spectrometry with tandem mass spectrometry (LC-MS/MS).
      The dialysate samples with methanol were directly analyzed by online column
      switching liquid chromatography. Using multiple reaction monitoring (MRM, product
      ions m/z 421 of m/z 657 for compound I, m/z 421 of m/z 643 for compound II, and
      m/z 407 of m/z 629 for compound III) on LC-MS/MS with electrospray ionization
      (ESI), opioidmimetics in rat brain dialysates were determined. Calibration curves
      of the method showed a good linearity in the range of 10-100 ng/ml for each
      compound. The limit of determination was estimated to be ca. 1 ng/ml for
      compounds II and III, and ca. 5 ng/ml for compound I, respectively. The precision
      of analysis showed coefficients of variation ranging from 4.7 to 10.4% at
      compound III concentration (10-100 ng/ml) in Ringer's solution. As a result, the
      procedure proved to be very suitable for routine analysis. The method was applied
      to the analysis of three opioidmimetics in the brain dialysate samples from rats
      treated with these compounds.

PMID- 15149613
TI  - Simultaneous determination of barbiturates in human biological fluids by direct
      immersion solid-phase microextraction and gas chromatography-mass spectrometry.
AB  - Simultaneous determination of seven barbiturates in human whole blood and urine
      by combining direct immersion solid-phase microextraction (DI-SPME) with gas
      chromatography-mass spectrometry (GC-MS) is presented. The main parameters
      affecting the DI-SPME process, such as SPME fibers, salt additives, pHs,
      extraction temperatures and immersion times were optimized for simultaneous
      determination of the drugs. The extraction efficiencies were 0.0180-0.988 and
      0.0156-2.76% for whole blood and urine, respectively. The regression equations of
      the drugs showed excellent linearity for both samples; the correlation
      coefficients (r(2)) were 0.994-0.999. The detection limits for whole blood were
      0.05-1 microg x ml(-1), and those for urine 0.01-0.6 microg x ml(-1). Actual
      quantitation could be made for pentobarbital in whole blood and urine obtained
      from volunteers, who had been orally administered a therapeutic dose of the drug.
      The DI-SPME/GC-MS procedure for barbiturates established in this study is simple
      and sensitive enough to be adopted in the fields of clinical and forensic
      toxicology.

PMID- 15149612
TI  - Monitoring of urinary acrolein concentration in patients receiving
      cyclophosphamide and ifosphamide.
AB  - Acrolein, the metabolite of cyclophosphamide and ifosphamide, irritates mucous
      membranes and is considered pathogenetically important in hemorrhagic cystitis.
      Increasing fluid intake or administering sodium 2-mercaptoethanesulfonate
      (mesna), a thiol compound, can reduce the risk of this complication. We measured
      urinary acrolein concentrations using headspace-solid-phase microextraction gas
      chromatography and mass spectrometry (headspace-SPME-GC-MS) in 19 patients
      receiving cyclophosphamide and ifosphamide (36 occasions). Peak acrolein
      concentrations occurred at 1-12h (mean +/- S.D., 5.0+/-2.7) after starting
      therapy, ranging from 0.3 to 406.8 nM (39.7+/-76.7), with varying patterns over
      time. Maintaining high urine volume was important for preventing increases in
      urinary acrolein concentration, as urinary acrolein concentration tended to rise
      as urine volume decreased. Urinalysis detected occult blood in three cases, but
      the patients had no clinical symptoms of hemorrhagic cystitis. In clinical trials
      involving cyclophosphamide and ifosphamide, monitoring of urinary acrolein
      concentration could indicate when to take heightened preventive measures against
      hemorrhagic cystitis.

PMID- 15149614
TI  - Detection and determination of reticuline and N-methylcoculaurine in the
      Annonaceae family using liquid chromatography-tandem mass spectrometry.
AB  - In Guadeloupe, the French West Indies, there is a high incidence of atypical
      parkinsonism or progressive supranuclear palsy, and all of the investigated
      patients had taken herbal tea or tropical fruits of the Annonaceae family. Local
      inhabitants consume the fruits, and also drink tea made from the leaves. In the
      present study, we used liquid chromatography-tandem mass spectrometry (LC/MS/MS)
      with multiple reaction monitoring (MRM) to detect low-molecular-weight neurotoxic
      benzylisoquinoline derivatives in the Annonaceae family. We detected reticuline
      and N-methylcoculaurine in every Annona muricata sample examined, except for pulp
      and seed. They were not detected in sweetsop fruits. Norreticuline was not
      detected in any sample. These three compounds were toxic to SH-SY5Y neuroblastoma
      cells and inhibited mitochondrial respiratory complex I. It is possible that
      uptake of the benzylisoquinoline derivatives reticuline and N-methylcoculaurine
      and their accumulation in the brain may be related to the pathogenesis of the
      local endemic disease.

PMID- 15149615
TI  - Shooting the messenger of antibiotic resistance: plasmid elimination as a
      potential counter-evolutionary tactic.

PMID- 15149616
TI  - Embracing the rat.

PMID- 15149617
TI  - Is Chlamydia associated with Alzheimer's?

PMID- 15149618
TI  - Antimicrobial peptides as carriers of drugs.

PMID- 15149619
TI  - Lewis Wolpert discusses development and depression. Interview by Joanne Clough.
AB  - Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of
      Anatomy and Developmental Biology at University College, London, UK. His research
      interests focus on the mechanisms that are involved in embryonic development.
      Lewis originally trained as a civil engineer in South Africa but in 1955 made the
      move to research in cellular biology at King's College, London. He was made a
      Fellow of the Royal Society in 1980 and awarded the CBE in 1990. Lewis was also
      made a Fellow of the Royal Society of Literature in 1999 and has presented
      science on both radio and TV for several years. He was awarded The Royal Society
      Michael Faraday Prize in 2000 for his contribution to the public understanding of
      science, most notably through his Chairmanship of the Committee for the Public
      Understanding of Science (COPUS; 1993-1998). He is the author of numerous books,
      including Malignant Sadness: The Anatomy of Depression, Principles of
      Development, The Unnatural Nature of Science and The Triumph of the Embryo. He
      also writes a regular column for The Independent.

PMID- 15149620
TI  - Drug discovery in autism: the need for a developmental context.

PMID- 15149621
TI  - Pharmacotherapy in autism: where to start?

PMID- 15149622
TI  - Express yourself.

PMID- 15149623
TI  - Implications of the allosteric kinetics of cytochrome P450s.
AB  - Drug metabolites can uniquely contribute to therapeutic efficacy, toxicity and
      drug-drug interactions. Therefore, the rates of formation and clearance of each
      metabolite are crucially important parameters in the net therapeutic profile of
      new drugs. However, the recent appreciation for the importance of drug metabolism
      has made it apparent that the understanding of the fundamental kinetic and
      biophysical properties of the enzymes that are responsible for catalyzing these
      reactions, the cytochrome P450s, is incomplete. The need to fully comprehend the
      complex allosteric behavior of these enzymes has fostered increased scrutiny of
      cytochrome P450s, which has subsequently resulted in major changes in the way
      that these enzymes are perceived at the molecular level.

PMID- 15149624
TI  - Application of statistical 'design of experiments' methods in drug discovery.
AB  - The use of 'design of experiments' (DoE) is a revolutionary approach to
      optimisation and screening of experimental parameters. Simple experimental
      designs and statistical tools for data analysis can provide much information
      about the system under investigation after only a few experiments. Such
      information can be key in decision-making for further experiments and can enable
      the development of robust and reliable protocols for chemical synthesis,
      analytical methods or biological assays. Coupling of design of experiments with
      modern high-throughput automation systems has the potential to maximise the
      capabilities of these systems and give increased productivity for many drug
      discovery applications.

PMID- 15149625
TI  - Outsourcing lead optimisation--the quiet revolution.
AB  - The outsourcing of lead optimisation services is a relatively new but growing
      market. Historically, pharmaceutical companies have been hesitant to outsource
      activities at the lead optimisation stage of the drug discovery process, but more
      recently this reticence has largely been put aside. As a result, a growing number
      of companies with diverse backgrounds and geographical locations are now
      competing to offer services in this sector. Currently, a particularly significant
      trend is the move towards 'off-shoring', which promises to drive further changes
      in this rapidly evolving market in the near future.

PMID- 15149630
TI  - Response to thalidomide in multiple myeloma: impact of angiogenic factors.
AB  - Thalidomide has antiangiogenic and immunomodulatory effects, mediated by several
      cytokines such as vascular endothelial growth factor (VEGF), fibroblastic growth
      factor (FGF-2), hepatocyte growth factor (HGF), interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha). Although extramedullary plasmacytomas (EMP)
      have a high vascularization, the response of these patients to thalidomide is
      controversial. Thirty-eight patients with refractory/relapsed MM were treated
      with thalidomide. Eleven patients had EMP when therapy was initiated. Serum
      specimens were obtained in patients before treatment was started and at the time
      of maximum response in responding patients or at thalidomide discontinuation in
      non-responders. Serum levels of VEGF, HGF and FGF-2 were determined in 18
      patients whereas IL-6 and TNF-alpha were measured in 19 patients. Sixteen of the
      38 patients (42%) responded to thalidomide. The response rate was significantly
      higher in patients without EMP (59% vs 0%, p = 0.0006 ). VEGF serum levels were
      significantly higher in responding patients. In contrast, baseline serum levels
      of HGF were significantly lower in responders. Neither VEGF nor HGF serum levels
      showed correlation with the presence of EMP. Baseline TNF-alpha serum levels were
      significantly lower in responding patients and in those without EMP. The serum
      levels of FGF-2 and IL-6 did not correlate with response to treatment or presence
      of EMP.

PMID- 15149631
TI  - High frequency of TNF alleles -238A and -376A in individuals from northern
      Sardinia.
AB  - The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and 
      238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been
      independently correlated with numerous diseases. Alleles TNF(-376A) and TNF(
      238A) are normally found throughout the world with very low frequencies. We
      investigated the frequency of these SNPs in Sicilian subjects hospitalized after
      traumatic brain injury and in three groups of subjects from northern Sardinia:
      healthy subjects and individuals with multiple sclerosis or ischemic stroke.
      While no significant difference was found between healthy and disease subjects,
      the frequency of TNF(-376A) and TNF(-238A) was elevated up to 10 times in
      Sardinia compared to Sicily and other populations throughout the world. These
      elevated frequencies may be the result of genetic drift or of selective pressure
      on TNF itself or on neighboring genes, including the HLA. Malaria, endemic to
      Sardinia until the end of the 1940s, and the bubonic plague, are among the
      possible causes of selection. These findings indicate that Sardinia is an ideal
      location to further elucidate the correlation between TNF or HLA polymorphisms
      and diseases, including multiple sclerosis and type-I diabetes, present with an
      unusually high frequency and co-morbidity in Sardinia.

PMID- 15149632
TI  - Th1 and Th2 cytokine immunomodulation by gangliosides in experimental autoimmune
      encephalomyelitis.
AB  - In experimental autoimmune encephalomyelitis, a classical model for multiple
      sclerosis, the cytokines provide the necessary signals to activate specific T
      cells for self-antigens. Gangliosides have multiple immunomodulatory activities,
      decreasing the lymphoproliferative responses and modulating cytokine production.
      Here, we tested the effects of gangliosides on the switching of Th1 to Th2
      cytokine expression, in spleen cells obtained from Lewis rats during the acute
      phase of EAE, and after recovery from the disease. For this purpose, total RNA
      from spleen cells was isolated and submitted to RT-PCR to investigate Th1 (IL-2,
      TNF-alpha, and IFN-gamma) and Th2/Th3 (IL-10 and TGF-beta) cytokine gene
      expression. Results demonstrate that the group treated with gangliosides displays
      mild disease, with low expression of IFN-gamma mRNA and high TGF-beta mRNA
      expression. We conclude that the gangliosides may modulate Th1 cells by the
      synthesis of cytokines shifting the profile to the Th2/Th3 phenotype.

PMID- 15149633
TI  - Interferon regulatory factor-1 (IRF-1) suppression and derepression during
      endometrial tumorigenesis and cancer progression.
AB  - Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene presumed to be
      involved in the control of cellular proliferation and transformation. Given that
      the IRF-1 is consistently expressed in the normally cycling endometrium, the
      question was raised of the possible role of IRF-1 in the genesis of endometrial
      adenocarcinoma. A series of 25 normal and 86 malignant endometria was
      investigated using immunohistochemical techniques and the anti-IRF-1 polyclonal
      antibody c-20. Normal endometrial glands were, indeed, consistently reactive with
      IRF-1. Excluding the invading tumor front, malignant endometria were deprived of
      IRF-1 reactivity, as 81 of the 86 cases (94.2%) were negative for this antigen.
      At the invading tumor front, however, IRF-1 was derepressed in tumor cells in 35%
      of the cases. This phenomenon was independent of the extent of lymphocytic
      response, but it was associated with thymidine phosphorylase (TP) expression.
      Furthermore, TP up-regulation and host's lymphocytic response in the area were
      directly associated. IRF-1 derepression by invading tumor cells was associated
      with poor prognosis, independently of FIGO stage. It is concluded that down
      regulation of IRF-1 is a constant finding in endometrial tumorigenesis. However,
      derepression of IRF-1 may occur in a subset of tumors, and this event is
      associated with TP up-regulation and aggressive tumor behavior.

PMID- 15149635
TI  - Human primary co-culture angiogenesis assay reveals additive stimulation and
      different angiogenic properties of VEGF and HGF.
AB  - Therapeutic angiogenesis aims to induce blood vessel growth in acute or chronic
      ischemic tissues and has gained tremendous interest over the last years. To study
      factors and combinations thereof that potentially induce or modify angiogenesis
      and to evaluate their therapeutic potential, various in vitro assays have been
      developed. Although endothelial cells have attracted most attention in these
      assays, they alone cannot complete vessel maturation since extracellular matrix
      (ECM) components and mesenchymal cells also play an important role in vascular
      development. To address this complexity we focussed on a human co-culture
      angiogenesis assay comprising primary endothelial cells as well as primary ECM
      producing fibroblasts. In this assay HGF and VEGF as single factors and combined
      were tested for the potential to induce an angiogenic response, which was
      detected by image analysis assessing the area, length and branches of the formed
      vascular structures. The results show that the cytokines HGF and VEGF both
      promote angiogenesis in this co-culture assay by inducing distinguishable
      patterns of vascular structures. VEGF increases the length, area and branch point
      number of induced vessels whereas HGF mediates exclusively vascular area growth
      resulting in vascular structures of enlarged diameter. Moreover, the combination
      of both cytokines results in an additive increase of vascular diameter.

PMID- 15149634
TI  - Combination of the pro-inflammatory cytokines IL-1, TNF-alpha and IL-17 leads to
      enhanced expression and additional recruitment of AP-1 family members, Egr-1 and
      NF-kappaB in osteoblast-like cells.
AB  - To determine the contribution of IL-1, TNF-alpha and IL-17 on AP-1, NF-kappaB and
      Egr-1 activation in cytokine induced bone destruction as observed in rheumatoid
      arthritis, we investigated the effect of these pro-inflammatory cytokines used
      alone or in combination on transcription factor activation in osteoblast-like ROS
      17/2.8 cells. The effects of each cytokine were measured by RT-PCR and
      immunocytochemistry. IL-1 and TNF-alpha induced most of these transcription
      factors while IL-17 had a weak effect. IL-1 and TNF-alpha induced egr-1 and all
      AP-1 member expression, except fosB and junD. These two cytokines used alone
      induced their nuclear translocation in 30 min, except for FosB and JunB. IL-17
      enhanced fra-2 and egr-1 mRNA expression, while nuclear localization was observed
      for Fra-1, JunD and NF-kappaB. More importantly, combination of low
      concentrations of these cytokines, with no effect separately, showed a
      synergistic effect on transcription and nuclear translocation of AP-1 members,
      Egr-1 and NF-kappaB. Moreover, cytokine combinations were associated with an
      enhanced recruitment of factors not expressed when cytokines were used alone. In
      conclusion, AP-1, Egr-1 and NF-kappaB pathways in osteoblast cells are very
      sensitive to the combined effect of pro-inflammatory cytokines through
      synergistic mechanisms.

PMID- 15149636
TI  - Porphyrin-DNA cross-linking agent hybrids: chemical synthesis and biological
      studies.
AB  - Three new porphyrin-DNA cross-linking conjugates 8, 9, and 10 have been
      synthesized. Their photoinduced DNA cleavage activity have been studied. The
      IC(50) values to THP-1 cells in the presence of porphyrin derivatives 8, 9, and
      10 with photoirradiation were 5.6, 88.4, and 61.8 nM, respectively.

PMID- 15149637
TI  - Discovering selective agonists of endothelial target for acetylcholine (ETA) via
      diversity-guided pharmacophore simplification and simulation.
AB  - Two types of lead structures for selective agonists of ETA, a biological target
      not yet fully elucidated, has first been discovered via diversity-guided
      pharmacophore simplification and simulation. And it is first demonstrated that
      potent selective ETA agonists might be useful for protection of endothelium and
      for prophylaxis and treatment of cardiovascular diseases with endothelial
      dysfunction such as atherosclerosis and thrombosis.

PMID- 15149638
TI  - A novel mixed-ligand antimycobacterial dimeric copper complex of ciprofloxacin
      and phenanthroline.
AB  - A novel mixed-ligand Cu(II) complex of ciprofloxacin (cfH) and phenanthroline, is
      found to crystallize as a dimeric moiety containing monocationic and dicationic
      species. Two such dimeric moieties are found in the same unit cell leading to a
      dicationic cluster. The higher negative redox potential for this cluster dampens
      its antimycobacterial activity against M. smegmatis.

PMID- 15149639
TI  - A new lead compound for abscisic acid biosynthesis inhibitors targeting 9-cis
      epoxycarotenoid dioxygenase.
AB  - 9-cis-Epoxycarotenoid dioxygenase (NCED), a key enzyme in abscisic acid (ABA)
      biosynthesis, cleaves the olefinic double bond of 9-cis-epoxycarotenoid. Several
      analogues of nordihydroguaiaretic acid (NDGA) were designed and synthesized, and
      their efficacy as inhibitors of NCED was examined. One of the synthesized
      compounds (20) was found to be an inhibitor of this enzyme, and inhibited ABA
      accumulation and stomatal closing, suggesting that 20 should be ABA biosynthesis
      inhibitor.

PMID- 15149640
TI  - Identification and optimization of novel partial agonists of neuromedin B
      receptor using parallel synthesis.
AB  - The design and parallel synthesis of potent, small molecule partial agonists of
      Neuromedin B receptor based on the 3-amino-2,3,4,9-tetrahydro-1H-carbazole-3
      carboxylic acid amide core is described.

PMID- 15149641
TI  - A novel series of potent and selective small molecule inhibitors of the
      complement component C1s.
AB  - Activation of the classical pathway of complement has been implicated in disease
      states such as hereditary angioedema, ischemia-reperfusion injury and acute
      transplant rejection. The trypsin-like serine protease C1s represents a pivotal
      upstream point of control in the classical pathway of complement activation and
      is therefore likely to be a useful target in the therapeutic intervention of
      these disease states. A series of thiopheneamidine-based inhibitors of C1s has
      been optimized to give a 70 nM inhibitor that inhibits the classical pathway of
      complement activation in vitro.

PMID- 15149642
TI  - Synthesis and pharmacological evaluation of piperidinoalkanoyl-1,2,3,4
      tetrahydroisoquinoline derivatives as novel specific bradycardic agents.
AB  - A series of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives were
      synthesized, and their bradycardic activities were investigated in the isolated
      right atria of guinea pigs and in conscious rats. These efforts identified the
      achiral compound 2f, which exhibited potent and long-lasting bradycardic activity
      with minimal effects on mean blood pressure in conscious rats.

PMID- 15149643
TI  - N-isoquinolin-5-yl-N'-aralkyl-urea and -amide antagonists of human vanilloid
      receptor 1.
AB  - Starting from a low micromolar agonist lead identified by high-throughput
      screening, series of N-isoquinolin-5-yl-N'-aralkyl ureas and analogous amides
      were developed as potent antagonists of human vanilloid receptor 1 (VR1). The
      synthesis and structure-activity relationships (SAR) of the series are described.

PMID- 15149644
TI  - Synthesis of 1,7-annulated indoles and their applications in the studies of
      cyclin dependent kinase inhibitors.
AB  - The synthesis of a novel series of 1,7-annulated indolocarbazoles 2 and 16 is
      described. These compounds were found to be potent cyclin dependent kinase
      inhibitors with good antiproliferative activity against two human carcinoma cell
      lines. These inhibitors also arrested tumor cells at the G1 phase and inhibited
      pRb phosphorylation.

PMID- 15149645
TI  - Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and
      6,8-disubstituted 2-naphthamidine urokinase inhibitors.
AB  - Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease
      urokinase plasminogen activator (uPA) are described. Direct attachment of five
      membered saturated or unsaturated rings improved inhibitor performance;
      substitution with sulfones further improved binding profiles. Combination of
      these substituents or of previously described NH-linked heteroaromatic rings with
      6-phenyl amide substituents provided further enhancements to potency and
      selectivity.

PMID- 15149646
TI  - The synthesis and antimicrobial evaluation of a new series of isoxazolinyl
      oxazolidinones.
AB  - A series of oxazolidinone antibacterial agents containing a 5-substituted
      isoxazol-3-yl moiety were synthesized via a nitrile oxide [3+2] dipolar
      cycloaddition reaction. These compounds were screened against a panel of
      susceptible and resistant Gram-positive organisms. Several analogs from this
      series were comparable to or more potent than linezolid in vitro.

PMID- 15149647
TI  - Bridgehead-methyl analog of SC-53116 as a 5-HT4 agonist.
AB  - Pyrrolizidine benzamide (+/-)-2, the bridgehead-methyl analog of SC-53116, was
      prepared and evaluated for 5-HT(4) agonism activity in the rat tunica muscularis
      (TMM) mucosae assay. Compound (+/-)-2 has an EC(50) of 449 nM in the TMM assay,
      as compared to 23 nM for SC-53116, and 66 nM for the racemate of SC-53116.

PMID- 15149649
TI  - Image contrast agents activated by prostate specific antigen (PSA).
AB  - A family of image contrast agent conjugates designed to undergo enzymatic
      activation has been synthesized. The agents underwent activation both with
      enzymatically active prostate specific antigen and alpha-chymotrypsin, releasing
      free fluorophore via cleavage of a three-component system.

PMID- 15149648
TI  - A TOPS-MODE approach to predict adenosine kinase inhibition.
AB  - The TOPological Sub-Structural Molecular Design (TOPS-MODE) approach has been
      applied to the study of the adenosine kinase inhibitory activity of pyrrolo[2,3
      d]pyrimidine nucleoside analogues. A model capable of describing around 77% of
      the variance in the experimental activity of 32 analogues of these compounds was
      developed with the use of the mentioned approach. In contrast, no one of nine
      different approaches, including the use of Constitutional, Topological, BCUT, 2D
      autocorrelations, geometrical, RDF, 3D Morse, WHIM, and GETAWAY descriptors were
      able to explain more than 70% of the variance in the mentioned property with the
      same number of descriptors. Although, statistically significant models were
      derived containing other descriptors than spectral moments still the best one
      fitted out model was find with these variables.

PMID- 15149650
TI  - Molecular modeling studies on the active binding site of the blood-brain barrier
      choline transporter.
AB  - The blood-brain barrier choline transporter may have utility as a drug delivery
      vector to the central nervous system. Surprisingly, this transporter has as yet
      not been cloned and expressed. We therefore initiated a 3D-QSAR study to develop
      predictive models for compound binding and identify structural features important
      for binding to this transporter. In vivo experimental data were obtained from in
      situ rat brain perfusion studies. Comparative molecular field analysis (CoMFA)
      and comparative molecular similarity index analysis (CoMSIA) methods were used to
      build the models. The best cross-validated CoMFA q(2) was found to be 0.47 and
      the non-cross-validated r(2) was 0.95. CoMSIA hydrophobic cross-validated q(2)
      was 0.37 and the non-cross-validated r(2) was 0.85. These models rendered a
      useful approximation for binding requirements in the BBB-choline transporter and,
      until such time as the cloned transporter becomes available, may have significant
      utility in developing a predictive model for the rational design of drugs
      targeted to the brain.

PMID- 15149651
TI  - Structural differences between paroxetine and femoxetine responsible for
      differential inhibition of Staphylococcus aureus efflux pumps.
AB  - In this study the chemical modification of paroxetine was employed to determine
      which structural differences between the paroxetine-like and femoxetine-like
      selective serotonin reuptake inhibitors is responsible for the differential
      potency of these agents in the inhibition of Staphylococcus aureus multidrug
      efflux pump systems.

PMID- 15149652
TI  - SAR study of a subtype selective allosteric potentiator of metabotropic glutamate
      2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide.
AB  - The major excitatory neurotransmitter in the Central Nervous System is L-glutamic
      acid. As a result much attention has been given to the discovery of selective
      modulators of both the ionotropic glutamate receptors (iGluRs) and the
      metabotropic glutamate receptors (mGluRs). In this study we describe a novel
      class of subtype selective allosteric potentiators of the mGlu2 receptor. An
      active compound N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide,
      LY181837, was identified in the course of compound screening. The synthesis of
      two series of analogs examined the structural requirements of the diaryl region
      of this compound. This SAR study also resulted in compounds with an increase in
      potency of over 100-fold where the most potent compound reported has EC(50)=14
      nM.

PMID- 15149653
TI  - Conformationally restricted analogs of deoxynegamycin.
AB  - Deoxynegamycin (1b) is a protein synthesis inhibitor with activity against Gram
      negative (GN) bacteria. A series of conformationally restricted analogs were
      synthesized to probe its bioactive conformation. Indeed, some of the constrained
      analogs were found to be equal or better than deoxynegamycin in protein synthesis
      assay (1b, IC(50)=8.2 microM; 44, IC(50)=6.6 microM; 35e(2), IC(50)=1 microM).
      However, deoxynegamycin had the best in vitro whole cell antibacterial activity
      (Escherichia coli, MIC=4-16 microg/mL; Klebsiella pneumoniae, MIC=8 microg/mL)
      suggesting that other factors such as permeation may also be contributing to the
      overall whole cell activity. A new finding is that deoxynegamycin is efficacious
      in an E. coli murine septicemia model (ED(50)=4.8 mg/kg), providing further
      evidence of the favorable in vivo properties of this class of molecules.

PMID- 15149654
TI  - Human ACAT-1 and -2 inhibitory activities of saucerneol B, manassantin A and B
      isolated from Saururus chinensis.
AB  - The sesquineolignan, saucerneol B (1), and dineolignans, manassantin A (2), and
      manassantin B (3), were isolated from the methanol extracts of Saururus chinensis
      root and elucidated by their spectroscopic data analysis. Compounds 1-3 inhibited
      hACAT-1 and hACAT-2 with IC(50) values of 43.0 and 124.0 microM for 1, of 39.0
      and 8.0 microM for 2, of 82.0 microM and only 32% inhibition at 1mM for 3,
      respectively. The EtOAc-soluble fraction, which contained compounds 1-3, of
      methanol extracts of S. chinensis exhibited strong cholesterol-lowering effect in
      high cholesterol-fed mice.

PMID- 15149655
TI  - Synthesis and activity of phosphinic tripeptide inhibitors of cathepsin C.
AB  - Phosphinic tripeptide analogues Gly-Xaapsi[P(O)(OH)CH(2)]-Gly have been developed
      as inhibitors of cathepsin C (DPP I), a lysosomal, papain-like cysteine protease.
      The target compounds were synthesised by addition of methyl acrylate to the
      appropriate phosphinic acids followed by the N-terminus elongation using mixed
      anhydride procedure. The latter step has been demonstrated to be a suitable
      method for N-terminal extension of the phosphinic pseudopeptide analogues without
      requirement of hydroxyphosphinyl protection. The title compounds appeared to be
      moderate inhibitors of the cathepsin C. However, although designed as transition
      state analogues, they surprisingly exhibited noncompetitive mode of binding to
      cathepsin C. Differences in kinetics of C-terminal acids and esters have been
      additionally observed.

PMID- 15149656
TI  - Lingshuiol, a novel polyhydroxyl compound with strongly cytotoxic activity from
      the marine dinoflagellate Amphidinium sp.
AB  - A novel polyhydroxy compound with a linear carbon-chain, lingshuiol (1), had been
      isolated from the cultured marine dinoflagellate Amphidinium sp. Its structure
      was elucidated by extensive analysis of 2D NMR spectral data. Lingshuiol
      possessed a powerful cytotoxic activity against A-549 and HL-60 cells in vitro
      with the IC(50) of 0.21 and 0.23 microM, respectively.

PMID- 15149657
TI  - Novel nonpeptidic inhibitors of HIV-1 protease obtained via a new multicomponent
      chemistry strategy.
AB  - Using a newly developed multicomponent chemistry strategy in combination with
      structure based drug design, a new class of HIV-1 protease inhibitors has been
      obtained.

PMID- 15149658
TI  - Synthesis and biological evaluation of novel beta-carboline derivatives as Tat
      TAR interaction inhibitors.
AB  - Four new beta-carboline derivatives were synthesized bearing guanidinium group or
      amino group-terminated side chain targeting the TAR element. Compounds 5 and 6
      with terminal guanidinium group showed inhibitory activities on Tat-TAR
      interaction as well as to HIV-1 in MT4 cells. Furthermore, capillary
      electrophoresis assay implied that compound 6 could not only bind to TAR but also
      hinder the Tat-TAR interaction.

PMID- 15149659
TI  - Development of an isotope-coded activity-based probe for the quantitative
      profiling of cysteine proteases.
AB  - Quantification studies of complex protein mixtures have been restricted mainly to
      whole cell extracts. Here we describe the synthesis of two sets of isotope-coded
      activity-based probes that allow quantitative functional proteomics experiments
      on the cathepsins.

PMID- 15149660
TI  - 2-Alkylsulfanyl estrogen derivatives: synthesis of a novel class of multi
      targeted anti-tumour agents.
AB  - A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from
      estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a
      similar anti-proliferative activity to the established 2-methoxyestradiol (2
      MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly
      enhanced anti-proliferative activity, combined with significant inhibition of
      steroid sulfatase, an enzyme target for the treatment of hormone-dependent
      tumours.

PMID- 15149661
TI  - Oxazolidinone: search for highly potent antibacterial.
AB  - A number of substituted piperazinyl oxazolidinone derivatives have been
      synthesized and their antibacterial activities were evaluated by MIC
      determination. A systematic SAR was carried out to get highly potent
      oxazolidinone derivatives.

PMID- 15149662
TI  - Synthesis and evaluation of nonpeptide substituted spirobenzazepines as potent
      vasopressin antagonists.
AB  - A series of substituted spirobenzazepines was prepared and evaluated as V(1a) and
      V(2) dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown
      to be not only potent inhibitors of vasopressin receptors, but also have
      exhibited an excellent overall pharmaceutical suitability profile.

PMID- 15149663
TI  - An efficient sequence for the preparation of small secondary amine hydrochloride
      salts for focused library generation without need for distillation or
      chromatographic purification.
AB  - Collections of small secondary amines for compound library generation can be
      efficiently prepared by amide reduction using BH(3)-THF or Red-Al followed by
      brief methanolysis, trapping with di-tert-butyl dicarbonate, and deprotection
      with 4M HCl in dioxane. The sequence requires no chromatography or distillation
      and provides multi-gram quantities of pure HCl salts in a short time.

PMID- 15149664
TI  - Exploring the possible binding sites at the interface of triosephosphate
      isomerase dimer as a potential target for anti-tripanosomal drug design.
AB  - To explore the possible binding sites at the interface of tripanosomal
      triosephosphate isomerase, fully flexible benzothiazoles were docked onto the
      dimer interface. Docking studies revealed that the most favorable interactions
      occur in the aromatic clusters of the dimeric form. Hence is purposed that the
      dimer disruption is not via Cys 15, as presented in last studies, but it could be
      carried out through the unstabilization of pi-pi interactions of two aromatic
      clusters present in the interface. These studies enable a novel alternative for
      rational structure-based anti-tripanosomal drug design.

PMID- 15149665
TI  - In vitro SAR of (5-(2H)-isoxazolonyl) ureas, potent inhibitors of hormone
      sensitive lipase.
AB  - A series of (5-(2H)-isoxazolonyl) ureas were developed as nanomolar inhibitors of
      hormone-sensitive lipase, an enzyme of potential importance in the treatment of
      diabetes.

PMID- 15149667
TI  - Structure-based design, synthesis, and antimicrobial activity of purine derived
      SAH/MTA nucleosidase inhibitors.
AB  - The structure-based design, synthesis, and biological activity of novel
      inhibitors of S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase
      are described. Using 6-substituted purine and deaza purines as the core
      scaffolds, a systematic and structure guided series of modifications provided low
      nM inhibitors with broad-spectrum antimicrobial activity.

PMID- 15149666
TI  - A new 2-carbamoyl pteridine that inhibits mycobacterial FtsZ.
AB  - The preparation of a new 2-carbamoyl pteridine, its activity data against FtsZ
      from M. tuberculosis (Mtb), and in vitro antibacterial data against Mtb strain
      H37Ra are presented.

PMID- 15149668
TI  - Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17-carboxyacryloyl
      ester derivatives of betulinic acid as anti-angiogenic agents.
AB  - New 3-O-acyl, 3-benzylidene, 3-hydrazone, 3-hydrazine, 17-carboxyacryloyl ester
      derivatives of betulinic acid (2-6, 8-11, 13, 17, 18, 21, and 22) were
      synthesized and evaluated in vitro for anti-angiogenic activity on endothelial
      cell cytotoxicity, specificity, and tube-formation ability. All derivatives
      reported here showed IC(50)<4 microg/mL. Compounds 3, 9, 10, 17, 21, and 22 have
      shown better cytotoxicity (IC(50)<1.2 microg/mL) than betulinic acid (1) and
      improved endothelial cell specificity (ECS>10) in some cases. Compounds 10, 17,
      and 18 have shown 20%, 32%, and 48% reduction in TLS, respectively, and were
      found better than betulinic acid (1). We have shown that 20,29-dihydrobetulinic
      acid derivatives have better anti-angiogenic activity as compared to betulinic
      acid or its other derivatives.

PMID- 15149669
TI  - 5-Alkyl-2-[(aryl and alkyloxylcarbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin
      4(3H)-ones as an unique HIV reverse transcriptase inhibitors of S-DABO series.
AB  - The introduction of a beta-carbonyl group to the C-2 side chain of S-DABO led to
      the finding of a series of novel potent anti-HIV agent. Some derivatives proved
      to be highly effective in inhibiting HIV-1 replication at nanomolar
      concentrations. Furthermore, the novel S-DABOs differ from the classical NNRTIs
      in that some compounds are active against both HIV-1 and HIV-2. They might
      interfere with another target or at least act on RT in a different way as
      compared to typical NNRTIs.

PMID- 15149670
TI  - Potential hypotensive agents: synthesis and hypotensive activity of oxime ethers
      derived from 1-naphthoxepines and related compounds.
AB  - The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and
      2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out.
      The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized
      cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a dose
      of 5mg/kg iv in anaesthetized cats.

PMID- 15149671
TI  - Design and synthesis of beta-amino-alpha-hydroxy amide derivatives as inhibitors
      of MetAP2 and HUVEC growth.
AB  - The rational design and synthesis of beta-amino-alpha-hydroxy amide derivatives
      as reversible inhibitors of methionine aminopeptidase-2 (MetAP2) with anti
      proliferative activity against human umbilical vein endothelial cells (HUVECs) is
      described.

PMID- 15149672
TI  - High-throughput identification of fucosyltransferase inhibitors using
      carbohydrate microarrays.
AB  - A noncovalent carbohydrate microarray was used to screen for possible inhibitors
      to fucosyltransferases, which are critical to the synthesis of inflammation
      mediators like sialyl Lewis x (SLe(x)). Inhibition was followed by observation of
      the transferred fucose on the carbohydrate array with the lectin Tetragonolobus
      purpureas. Of these compounds, four inhibitors with nanomolar Ki(s) were
      discovered, with three of the top five inhibitors exhibiting a common
      architecture.

PMID- 15149673
TI  - Synthesis and structure-activity relationships of 3-substituted 1,4-dihydro-4-oxo
      1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents.
AB  - In order to obtain clinically useful antitumor agent, we have designed and
      synthesized various 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8
      naphthyridines, and evaluated their cytotoxic activity. The series of novel 3
      substituted derivatives synthesized in this study showed good antitumor activity
      against murine P388 leukemia. Particularly, the 3-formyl 1,8-naphthyridine
      displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine
      against murine and human tumor cell lines as well as in vivo test for mouse
      leukemia. These results demonstrate that the carboxy group at the C-3 position of
      1,8-naphthyridine ring is not essential for antitumor activity. In addition, the
      trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was
      different from that of antibacterial activity.

PMID- 15149674
TI  - Benzimidazoles as new potent and selective DP antagonists for the treatment of
      allergic rhinitis.
AB  - A series of 2-substituted N-benzyl benzimidazole containing molecules has been
      synthesized and its structure-activity relationship for the human DP receptor has
      been evaluated. Selective DP antagonists with nanomolar potency for the DP
      receptor were identified in this novel series of benzimidazoles.

PMID- 15149675
TI  - First total synthesis of structurally unique flavonoids and their strong anti
      inflammatory effect.
AB  - The first total synthesis of structurally unique flavonoids 1a and 1b is
      described. These compounds showed very strong anti-inflammatory effect against
      delayed hypersensitivity in a mouse model.

PMID- 15149676
TI  - Development of l-3-aminotyrosine suitably protected for the synthesis of a novel
      nonphosphorylated hexapeptide with low-nanomolar Grb2-SH2 domain-binding
      affinity.
AB  - Synthesis of orthogonally protected (2S)-2-amino-3-(3-amino-4-hydroxy-phenyl)
      propionic acid (10) suitable for solid phase peptide synthesis and its first use
      for the preparation of nonphosphorylated Grb2-SH2 domain antagonists (4a-c) are
      reported. The 3-aminotyrosine containing sulfoxide-cyclized hexapeptide (4b)
      exhibited potent Grb2-SH2 domain binding affinity with IC50 = 50 nM, which
      represents the highest affinity yet reported for a peptide inhibitor against Grb2
      SH2 domain with only 6 residues free of phosphotyrosine or phosphotyrosine
      mimics. This potent small peptidomimetic 4b may be representative of a new class
      of therapeutically relevant Grb2-SH2 domain-directed agents, and acts as a
      chemotherapeutic lead for the treatment of erbB2-related cancers.

PMID- 15149677
TI  - New highly active taxoids from 9 beta-dihydrobaccatin-9,10-acetals. Part 5.
AB  - To improve the metabolic stability of 3, which exhibited both in vitro antitumor
      activity and in vivo efficacy by both iv and po administration, we designed and
      synthesized new taxane analogues. Most of the synthetic compounds maintained
      excellent antitumor activity and were scarcely metabolized by human liver
      microsomes. And some compounds exhibited potent antitumor effects against B16
      melanoma BL6 in vivo by both iv and po administration similarly to 3.

PMID- 15149679
TI  - Critical structural motif for the catalytic inhibition of human topoisomerase II
      by UK-1 and analogs.
AB  - Three new analogs of UK-1 have been synthesized and their efficacies as
      topoisomerase II inhibitors have been determined. Results show that UK-1 and two
      of these analogs are catalytic inhibitors of topo II and identifies a critical
      structure motif necessary for enzyme inhibition.

PMID- 15149678
TI  - 1,7-annulated indolocarbazoles as cyclin-dependent kinase inhibitors.
AB  - The synthesis and kinase inhibitory activity of a series of novel 1,7-annulated
      indolocarbazoles 6 and 16 is described. These compounds exhibited potent
      inhibitory activity against cyclin-dependent kinase 4 and good antiproliferative
      activity in a human colon carcinoma cell line.

PMID- 15149680
TI  - Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1
      isoquinolinylguanidines.
AB  - A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA
      with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4
      halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic
      acid group. Compound 13j (UK-356,202) combines excellent potency and selectivity,
      and has been selected as a candidate for clinical evaluation.

PMID- 15149681
TI  - Synthesis and CB1 receptor activities of novel arachidonyl alcohol derivatives.
AB  - Novel derivatives of arachidonyl alcohol were synthesized and evaluated for their
      CB1 receptor activity by [(35)S]GTP(gamma)S assay using rat cerebellar membranes.

PMID- 15149682
TI  - Potent and selective, sulfamide-based human beta 3-adrenergic receptor agonists.
AB  - A series of sulfamide-based analogs related to L-796568 were prepared and
      evaluated for their biological activity at the human beta(3)-adrenergic receptor
      (AR). This modification allows for a significant reduction in molecular weight,
      while maintaining single-digit nanomolar potencies at the beta(3)-AR and high
      selectivities versus the beta(2)- or beta(3)-AR.

PMID- 15149683
TI  - 3,3(')-Oxybis(dimethoxytrityl chloride) (O-DMTCl): synthesis and applications of
      a novel bifunctional protecting group.
AB  - 3,3(')- Oxybis(dimethoxytrityl chloride) (O-DMTCl) was synthesized as a novel,
      acid-labile bifunctional protecting reagent. The reactions of O-DMTCl with base
      protected ribonucleosides afforded unexpectedly 2('),5(')-cyclic protected
      ribonucleosides in addition to the expected 3('),5(')-cyclic protected
      ribonucleosides in good yields.

PMID- 15149684
TI  - 3-(7-Azaindolyl)-4-arylmaleimides as potent, selective inhibitors of glycogen
      synthase kinase-3.
AB  - A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was
      synthesized and evaluated for activity against GSK-3beta and selectivity versus
      PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c
      potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited
      excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound
      17c was also highly selective against 68 other protein kinases. In a cell-based
      functional assay, both 14 and 17c effectively increased glycogen synthase
      activity by inhibiting GSK-3beta.

PMID- 15149685
TI  - Novel thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine
      mimetics: optimization via modification of P1 and P3 moieties.
AB  - Optimization of lead compounds 1 and 2 resulted in novel, selective, and potent
      thrombin inhibitors incorporating weakly basic heterobicyclic P(1)-arginine
      mimetics. The design, synthesis, and biological activity of racemic thrombin
      inhibitors 17-29 and enantiomerically pure thrombin inhibitors 30-33 are
      described. The arginine side-chain mimetics used in this study are 4,5,6,7
      tetrahydro-1,3-benzothiazol-2-amine, 4,5,6,7-tetrahydro-2H-indazole, and 2-imino
      4,5,6,7-tetrahydro-1,3-benzothiazol-3(2H)-ylamine.

PMID- 15149686
TI  - The monoethyl ester of meconic acid is an active site inhibitor of HCV NS5B RNA
      dependent RNA polymerase.
AB  - Screening of the in-house sample collection for compounds with HCV NS5B RNA
      dependent RNA polymerase inhibition led to the identification of a new lead.
      Afterwards, we discovered that the screening lead, rather than containing the
      expected structure 1, was comprised of roughly a 1:1 mixture of meconic acid 2
      and its monoethyl ester 3, with all inhibitory potency residing with 3. We
      propose that this compound shares critical common features for activity with
      alpha,gamma-diketoacids inhibitors previously discovered by our group. SAR around
      this molecule will be presented to provide an improved basis for structure-based
      ligand design.

PMID- 15149687
TI  - A novel 18 beta-glycyrrhetinic acid analogue as a potent and selective inhibitor
      of 11 beta-hydroxysteroid dehydrogenase 2.
AB  - Using 18beta-glycyrrhetinic acid as a template, the synthesis of a series of
      secondary amides at the 30-position is described and the effects of these
      modifications on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type
      1 and 2 from the rat are investigated. An isoform selective inhibitor has been
      discovered and compound 5, N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean
      12-en-30-oic acid amide, is highlighted as a very potent and selective inhibitor
      of 11beta-hydroxysteroid dehydrogenase 2 with an IC(50)=4 pM.

PMID- 15149688
TI  - 2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: a novel class
      of small molecule heparanase inhibitors.
AB  - A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are
      described as inhibitors of the endo-beta-glucuronidase heparanase. Several of the
      compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2
      yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display
      potent heparanase inhibitory activity (IC(50) 200-500 nM) and have high
      selectivity (>100-fold) over human beta-glucuronidase. They also show anti
      angiogenic effects. Such compounds should serve as useful biological tools and
      may provide a basis for the design of novel therapeutic agents.

PMID- 15149689
TI  - Long chain amines and long chain ammonium salts as novel inhibitors of dynamin
      GTPase activity.
AB  - We examined a number of ligands with the view of inhibiting the GTPase activity
      of dynamin. Dynamin contains a pleckstrin homology (PH) domain that interacts
      with lipids. We report a series of simple lipid-like molecules that display
      moderate inhibitory activity. Inhibitory activity is linked to chain length and
      quaternarization of the terminal amine. A change in the counterion, Cl versus Br
      or I, had little effect on potency. However, introduction of a hydrophobic collar
      proximal to the charged site was beneficial to dynamin GTPase inhibitory action.
      The most potent compound was myristoyl trimethyl ammonium bromide (MTMAB, IC(50)
      3.15 microM).

PMID- 15149690
TI  - Simple and an efficient method for the synthesis of 1-[2-dimethylamino-1-(4
      methoxy-phenyl)-ethyl]-cyclohexanol hydrochloride: (+/-) venlafaxine racemic
      mixtures.
AB  - A novel synthetic method was developed for the synthesis of venlafaxine using
      inexpensive reagents. An improvement in the method, in the yield was achieved for
      the conversion of the venlafaxine. This is an improved version, simple and
      efficient method for the large-scale synthesis of venlafaxine.

PMID- 15149691
TI  - Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor
      associated isoenzyme IX with aromatic and heterocyclic sulfonamides.
AB  - QSAR study on the tumor-associated transmembrane carbonic anhydrase IX (CA IX)
      isoenzyme has been made using a large pool of distance-based topological indices
      : W, Sz, PI (0)chi, (1)chi, (2)chi,(0)chi(v), (1)chi(v), (2)chi(v). A combined
      set of 32 aromatic and heterocyclic compounds, including the six clinically used
      derivatives: acetazolamide, methazolamide, ethoxyzolamide, dichlorophenamide,
      dorzolamide, and brinzolamide are used for this purpose. The results have shown
      that the inhibition of the tumor-associated isoenzyme IX with aromatic and
      heterocyclic sulfonamides can be modeled excellently in multiparametric
      regression after introduction of indicator parameters. The predictive power of
      the models is discussed using probable error of correlation (PE), variance
      inflation factor (VIF), and cross-validation parameters: PRESS, SSY, r(2) (cv)
      (S) PRESS, and PSE. This is the first report on QSAR study on inhibition of tumor
      associated isoenzyme IX.

PMID- 15149692
TI  - Design and synthesis of dysidiolide analogs from vitamin D3: novel class of
      Cdc25A inhibitors.
AB  - Potent dysidiolide analogs were synthesized by structural hybridization of
      dysidiolide and vitamin D(3). These analogs exhibited strong inhibitory activity
      toward dual-specificity phosphatase Cdc25A (IC(50)=0.44-0.89 microM).

PMID- 15149693
TI  - The effect of 6-substituted-4',4"-difluorobenztropines on monoamine transporters
      and the muscarinic M1 receptor.
AB  - A series of racemic 6-hydroxy and carboalkoxy substituted-4('),4"
      difluorobenztropines was synthesized and evaluated for binding at the dopamine
      (DAT), the serotonin (SERT), the norepinephrine (NET) transporters, and the
      muscarinic M1 receptor. Each of the analogues displaced [(3)H]WIN 35,428 (DAT)
      with a range of affinities from 5.81 to 175 nM and [(3)H]pirenzepine (M1), with a
      range of affinities ( K(i)= -8430 nM). Binding affinities at the SERT and the NET
      were generally low.

PMID- 15149694
TI  - Novel inhibitors of bacterial protein synthesis: structure-activity relationships
      for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants.
AB  - Structure-activity relationships for a recently discovered novel ribosome
      inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to
      optimize protein synthesis inhibitory activity of the series through modification
      of positions 3 and 4 of the naphthyridone lead template resulted in the
      identification of several biochemically potent analogues. A lack of corresponding
      whole cell antibacterial activity is thought to be a consequence of poor cellular
      penetration as evidenced by the enhancement of activity observed for a lead
      analogue tested in the presence of a cell permeabilizing agent.

PMID- 15149695
TI  - New substituted triaza-benzo[cd]azulen-9-ones as promising phosphodiesterase-4
      inhibitors.

PMID- 15149697
TI  - Thiol-based SAHA analogues as potent histone deacetylase inhibitors.
AB  - In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a
      series of thiol-based compounds modeled after suberoylanilide hydroxamic acid
      (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated.
      Compound 6, in which the hydroxamic acid of SAHA was replaced by a thiol, was
      found to be as potent as SAHA, and optimization of this series led to the
      identification of HDAC inhibitors more potent than SAHA.

PMID- 15149696
TI  - Comparison of inhibitory activity of isomeric triazolopyridine derivatives
      towards adenosine receptor subtypes or do similar structures reveal similar
      bioactivities?
AB  - The synthesis of an array of 8-amino-2-aryl-[1,2,4]triazolo[1,5-a]pyridine-6
      carboxyl amide derivatives is described for the first time. A subset of 20
      derivatives were compared to their isomeric 5-amino-2-aryl-[1,2,4]triazolo[1,5
      a]pyridine-7-carboxyl amide counterparts with regard to their potential to
      inhibit the human adenosine 2a (hA2a) receptor and their selectivity against the
      human adenosine 1 (hA1) receptor. Based on the analysis of H-bond donor/acceptor
      capabilities of the isomeric triazolopyridine pairs it can be concluded that the
      H-bond donor strength of the free amino functionality is the main determinant for
      hA2a inhibitory activity and hA1 selectivity.

PMID- 15149698
TI  - The first synthesis of glucosylgalactosyl hydroxylysine (Glu-Gal-Hyl), an
      important biological indicator of collagen turnover.
AB  - This paper reports the first chemical synthesis of alpha-D-glucopyranosyl-(1-->2)
      beta-D-galactopyranosyl-O-hydroxylysine, a glycoside of hydroxylysine important
      as indicator of skin and bone collagen turnover, starting with commercial
      compounds.

PMID- 15149699
TI  - Synthesis of analogues of a potent antitumor saponin OSW-1.
AB  - A series of side chain analogues (5a-e), a 22-glycosylated isomer (10), and
      16beta-O-l-arabinosyl (13a) or 16beta-O-d-xylosyl (13b) analogues of OSW-1 were
      synthesized. All analogues were found to be less cytotoxic against breast and
      endometrial cancer cell lines than the natural product.

PMID- 15149700
TI  - Carbonic anhydrase inhibitors. Inhibition of the zinc and cobalt gamma-class
      enzyme from the archaeon Methanosarcina thermophila with anions.
AB  - Anions represent the second class of inhibitors of the zinc enzyme carbonic
      anhydrase (CA, EC 4.2.1.1), in addition to sulfonamides, which possess clinical
      applications. The first inhibition study of the zinc and cobalt gamma-class
      enzyme from the archaeon Methanosarcina thermophila (Cam) with anions is reported
      here. Inhibition data of the alpha-class human isozymes hCA I and hCA II
      (cytosolic) as well as the membrane-bound isozyme hCA IV with a large number of
      anionic species such as halides, pseudohalides, bicarbonate, carbonate, nitrate,
      nitrite, hydrosulfide, bisulfite, and sulfate, etc., are also provided for
      comparison. The best Zn-Cam anion inhibitors were hydrogen sulfide and cyanate,
      with inhibition constants in the range of 50-90 microM, whereas thiocyanate,
      azide, carbonate, nitrite, and bisulfite were weaker inhibitors (K(I)s in the
      range of 5.8-11.7 mM). Fluoride, chloride, and sulfate do not inhibit this enzyme
      appreciably up to concentrations of 200 mM, whereas the substrate bicarbonate
      behaves as a weak inhibitor (K(I)s of 42 mM). The best Co-Cam inhibitor was
      carbonate, with an inhibition constant of 9 microM, followed by nitrate and
      bicarbonate (K(I)s in the range of 90-100 microM). The metal poisons were much
      more ineffective inhibitors of this enzyme, with cyanide possessing an inhibition
      constant of 51.5mM, whereas cyanate, thiocyanate, azide, iodide, and hydrogen
      sulfide showed K(I)s in the range of 2.0-6.1mM. As for Zn-Cam, fluoride,
      chloride, and sulfate are not inhibitors of Co-Cam. These major differences
      between the two gamma-CAs investigated here can be explained only in part by the
      different geometries of the metal ions present within their active sites.

PMID- 15149701
TI  - Nucleosides and nucleotides. Part 226: alternate-strand triple-helix formation by
      3'-3'-linked oligodeoxynucleotides composed of asymmetrical sequences.
AB  - In this paper, we describe the synthesis of the 3'-3'-linked oligonucleotides
      connected with pentaerythritol composed of asymmetrical sequences. Stability of
      the triplexes between these oligonucleotides and the DNA targets involving the
      adjacent oligopurine domains on alternate strands was investigated using the
      electrophoretic mobility shift assay (EMSA) and DNase I footprinting experiment.
      It was found that the 3'-3'-linked oligonucleotides composed of asymmetrical
      sequences formed the stable antiparallel triplexes with the DNA targets as
      compared with the unlinked oligonucleotides. Thus, oligonucleotides linked with
      pentaerythritol would be useful as antigene oligonucleotides for DNA targets
      consisting of the alternating oligopyrimidine-oligopurine sequences.

PMID- 15149702
TI  - Preparation of alkylation agents for bulged DNA microenvironments.
AB  - A designed molecule with capacity to alkylate DNA bulges has been prepared from
      readily available starting materials. The spirocyclic template utilized was
      designed on the basis of established architectures, and equipped with a mustard
      alkylating group. Preliminary studies confirm alkylation of specific bulged
      sequences, paving the way for second generation substrates with higher affinity.

PMID- 15149704
TI  - N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and
      conformationally restrained indole analogues: development of calindol as a new
      calcimimetic acting at the calcium sensing receptor.
AB  - The synthesis and calcimimetic activities of two new families of compounds are
      described. The most active derivatives of the first family, N(2)-(2-chloro-(or 4
      fluoro-)benzyl)-N(1)-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamine (4b and
      4d, respectively, tested at 10 microM) produced 98+/-6% and 95+/-4%,
      respectively, of the maximal stimulation of [(3)H]inositol phosphates production
      obtained by 10mM Ca(2+) in CHO cells expressing the rat calcium sensing receptor
      (CaSR). The second family of calcimimetics was obtained by conformationally
      restraining the compounds of type 4 to provide the 2-aminomethyl derivatives 5.
      One of these compounds, (R)-2-[N-(1-(1-naphthyl)ethyl)aminomethyl]indole ((R)-5a,
      calindol), displayed improved calcimimetic activity compared to 4b and 4d as well
      as stereoselectivity. In the presence of 2mM Ca(2+), calindol stimulated
      [(3)H]inositol phosphates accumulation with an EC(50) of 1.0+/-0.1 or 0.31+/-0.05
      microM in cells expressing the rat or the human CaSR, respectively. The
      calcimimetic activities of these novel compounds were shown to be due to a
      specific interaction with the CaSR.

PMID- 15149703
TI  - Anti-AIDS agents. Part 58: synthesis and anti-HIV activity of 1-thia-di-O-(-)
      camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues.
AB  - Two 1-thia-DCK analogues (9a and 9b) were synthesized and evaluated for
      inhibition of HIV-1 replication in H9 lymphocytes. Compound 9a showed excellent
      anti-HIV activity with an EC(50) value of 0.00012 microM and therapeutic index of
      1408000. Compound 9b was less active with EC(50) and TI values of 3.11 microM and
      62.3, respectively. The bioassay results indicated that thia-DCK analogues merit
      attention as potential HIV-1 inhibitors.

PMID- 15149705
TI  - Potent S1P receptor agonists replicate the pharmacologic actions of the novel
      immune modulator FTY720.
AB  - Alteration in lymphocyte trafficking and prevention of graft rejection in rodents
      observed on exposure to FTY720 (1) or its corresponding phosphate ester 2 can be
      induced by the systemic administration of potent sphingosine-1-phosphate receptor
      agonists exemplified by 19. The similar S1P receptor profiles of 2 and 19 coupled
      with their comparable potency in vivo supports a connection between S1P receptor
      agonism and immunosuppressive efficacy.

PMID- 15149706
TI  - A new approach to the synthesis of optically active alkylated adenine
      derivatives.
AB  - A new synthesis of chiral acyclic nucleoside and nucleotide analogues starting
      from d(-)- or l(+)-riboses was proposed. Antiviral properties of the synthesized
      compounds towards the pox virus family were evaluated.

PMID- 15149707
TI  - Symptom subtypes of obsessive-compulsive disorder and their relation to
      dissociation.
AB  - We examined relations between obsessive-compulsive disorder (OCD) symptoms and
      dissociation in three studies. Studies 1 and 2 established a strong level of
      convergence between our two OCD symptom measures. Specific types of symptoms
      showed a clear convergent/discriminant pattern, indicating that they can be
      meaningfully distinguished from one another. In both studies, dissociation
      correlated more strongly with checking and obsessive intrusions than with
      cleaning, ordering, and hoarding. Moreover, these associations remained
      substantial even after controlling for neuroticism (Study 1) and other types of
      anxiety (Study 2). In Study 3, we replicated our key findings in a psychiatric
      outpatient sample, indicating that they are generalizable to clinical
      participants. Taken together, our results (a) establish a strong link between
      dissociation and OCD, and (b) illustrate the importance of analyzing different
      types of OCD symptoms separately.

PMID- 15149708
TI  - A brief group cognitive-behavioral intervention for social phobia in childhood.
AB  - Twenty-three preadolescent children (ages 8-11) meeting criteria for social
      phobia were randomly assigned to either a 3-week cognitive-behavioral group
      intervention or a wait-list control group. The intervention consisted of
      psychoeducation, cognitive strategies, and behavioral exposure. Outcome measures
      included diagnostic interview as well as parent and child report measures of
      anxiety and depression. Improvements were observed at posttest, with results
      stronger for parent report and interviewer ratings than for child self-report. At
      3-week follow-up, children receiving the intervention demonstrated significant
      improvements on the majority of child, parent, and interviewer reports of social
      anxiety and related symptoms relative to wait-list participants. Preliminary
      support is provided for the utility of a brief intervention for preadolescent
      children with social phobia. Limitations and implications for future research are
      discussed.

PMID- 15149709
TI  - Probability and cost estimates for social and physical outcomes in social phobia
      and panic disorder.
AB  - Individuals with Social Phobia (SP) (n = 23) and Panic Disorder (n = 22), and a
      non-anxious comparison (NAC) group (n = 62) rated the probability and cost of
      negative outcomes in the physical and the social domains. Overall, participants
      rated physical events as less probable but more costly than social events.
      Compared to the non-anxious group, participants with Social Phobia made
      significantly higher probability and cost estimates for social events, but not
      for physical events. Multiple regression analyses demonstrated that perceived
      cost of negative social events was the strongest unique predictor of scores on
      the Fear of Negative Evaluation Scale (FNE). Participants with Panic Disorder
      made significantly higher probability and cost estimates for both physical and
      social outcomes, compared to non-anxious participants. Both physical probability
      and social cost estimates predicted scores on the Body Sensations Questionnaire
      (BSQ). Findings support the disorder-specificity of cognitive biases in Social
      Phobia, but suggest that individuals with Panic Disorder have a wider range of
      judgment biases than previously thought.

PMID- 15149710
TI  - Anxious and depressive symptoms and children's judgements of their own and
      others' interpretation of ambiguous social scenarios.
AB  - This study investigated associations between anxious and depressive symptoms in 7
      and 9-year-olds and their judgements of intention. It asked children to judge
      how a protagonist (other judgement) and they themselves (self-judgement) would
      interpret the intention of a second character, where this intention was
      ambiguously negative or benign. The results showed that levels of self-report
      depressive symptoms predicted an increase in the number of negative
      interpretations for self (but not for other) judgements. In comparison, increased
      levels of parent-report anxiety symptoms predicted an increase in number of
      negative interpretations for other (but not for self) judgements.

PMID- 15149711
TI  - How much do sample characteristics affect the effect size? An investigation of
      studies testing the treatment effects for social phobia.
AB  - In spite of the success of cognitive behavioral therapy for social phobia in
      research studies, it remains unclear whether interventions will remain successful
      in the routine of clinical practice, where patients might differ from those in
      research samples. This study investigates the possibility that higher effect
      sizes are achieved under typical research conditions. Thirty studies testing
      treatment effects for social phobia are re-examined by categorizing them
      according to the quality and amount of applied sample restriction and laboratory
      study characteristics. The results indicate that even accumulation of sample
      restriction, such as excluding patients with comorbid disorders or being outside
      a certain age range, does not have any predictive value for treatment effect.
      However, there was a relevant tendency for studies applying a row of laboratory
      treatment conditions, such as recruiting patients by advertisements, applying
      treatment in university settings, and using specifically trained therapists, to
      achieve higher effect sizes.

PMID- 15149712
TI  - Specific phobia of illness: search for a new subtype.
AB  - Specific phobia of illness makes its appearance in DSM-IV as a new diagnostic
      subtype, separate from hypochondriasis. A review of the literature indicates
      that, while there is some support for this new category, studies have not as yet
      been done that could provide validation. Illness phobia appears to be a
      significant problem; it is prevalent in the general population and is associated
      with distress and impairment, including interference with medical care. It
      appears to be associated with older age, physical illness, and female gender.
      Group comparisons are needed showing that persons with this phobia can be
      distinguished from hypochondriasis on the basis of these and other demographic
      and illness features. We outline a research agenda for demonstrating this
      separation.

PMID- 15149714
TI  - Insomnia and generalized anxiety disorder: effects of cognitive behavior therapy
      for gad on insomnia symptoms.
AB  - Although clinical practice suggests that sleep complaints are frequent among
      patients with generalized anxiety disorder (GAD), frequency, severity, types of
      insomnia complaints, and relationship to GAD diagnosis severity in patients
      diagnosed using Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
      criteria are not well documented. Clinical data about the impact on insomnia
      symptoms of treating GAD worries are also lacking. The present study examined
      these aspects in 44 GAD patients who participated in a treatment study
      specifically addressing excessive worries through CBT interventions. All patients
      were assessed using a structured clinical interview and the Anxiety Disorder
      Interview Schedule-IV (ADIS-IV). They also completed anxiety and insomnia
      inventories, including the Insomnia Severity Index (ISI), a self-report measure
      which assesses insomnia type, severity and interference with daily life. Among
      this sample, 47.7% reported difficulties initiating sleep, 63.6% reported
      difficulties maintaining sleep, and 56.8% complained of waking too early in the
      morning. The majority of these patients (86.5%) reported never having experienced
      insomnia without having excessive worries. However, insomnia severity and GAD
      severity were not correlated. In this sample, patients with severe GAD did not
      necessarily report more severe insomnia symptoms. Regarding treatment impact on
      insomnia complaints, ISI post-treatment scores were significantly lower after
      treatment. Mean post-treatment scores almost reached ISI's "absence of clinical
      insomnia" category. Results indicate that this CBT package for GAD does have a
      significant impact on sleep quality even if sleep disturbances were not
      specifically addressed during treatment.

PMID- 15149713
TI  - Investigating the construct validity of the SPAI-C: comparing the sensitivity and
      specificity of the SPAI-C and the SAS-A.
AB  - Investigates the construct validity of the Social Phobia and Anxiety Inventory
      for Children (SPAI-C) by comparing its sensitivity and specificity with another
      self-report measure of social anxiety, the Social Anxiety Scale for Adolescents
      (SAS-A). Participants were 252 adolescents (124 males and 128 females) 13-17
      years old. Adolescents completed the SPAI-C and the SAS-A and were interviewed
      using the Anxiety Disorders Interview Schedule for DSM-IV: Child Version (ADIS
      IV:C). Parents were also interviewed and composite diagnoses were formed. Youth
      were classified as socially phobic or non-anxious based on these composite
      diagnoses. By comparing clinical cutoff scores with diagnostic group
      classification, the sensitivity and the specificity of the SPAI-C and SAS-A were
      compared. Results indicated that the SPAI-C was a more sensitive measure than the
      SAS-A (61.5% vs. 43.6%) providing evidence of the scale's construct validity. The
      two measures were similar with regard to specificity (82.7% for both).
      Implications of these results for assessment and research are discussed.

PMID- 15149716
TI  - Investigation of influence of gas atmosphere and pressure upon non-contact atomic
      force microscopy.
AB  - Resonance measurements and atomic force microscopy (AFM) observations were
      carried out by the non-contact AFM operating in various gas atmospheres
      (hydrogen, helium, nitrogen and argon) over the range of pressures from 0.1 to
      1.1 MPa. In each atmosphere, the resonance frequency of the AFM cantilever
      depended on the pressure of gases studied. The plots of the relative resonance
      frequency at a constant pressure vs. the gas density gave a straight line. It was
      found that the characteristic of the resonance frequency for the AFM cantilever
      were dependent on the density of the gas species. The resolution of the AFM was
      hardly influenced by the gas atmosphere under the present experimental
      conditions.

PMID- 15149715
TI  - The tuning of a Zernike phase plate with defocus and variable spherical
      aberration and its use in HRTEM imaging.
AB  - With the advent of the double-hexapole aberration corrector in transmission
      electron microscopy the spherical aberration of the imaging system has become a
      tunable imaging parameter like the objective lens defocus. Now Zernike phase
      plates, altering the phase of the diffracted electron wave, can be approximated
      more perfectly than with the lens defocus alone, and the amount of phase change
      can be adjusted within wide limits. The tuning of the phase change allows an
      optimum contrast transfer in high-resolution imaging even for thick crystalline
      objects, thus surpassing the limits of the well-known Scherzer lamda/4 phase
      plate to the imaging of thin objects. The optimum values for the spherical
      aberration and the lens defocus are derived, and the limits and imperfections of
      the approximation explored. A mathematical link to the channelling approximation
      of high-energy electron diffraction shows how the image contrast of atomic
      columns can be improved systematically within wide thickness limits. Depending on
      the specimen thickness different combinations of spherical aberration and defocus
      are favourable: positive spherical aberration with an underfocus, zero spherical
      aberration with zero defocus, as well as negative spherical aberration with an
      overfocus.

PMID- 15149717
TI  - Shear force distance control in a scanning near-field optical microscope: in
      resonance excitation of the fiber probe versus out of resonance excitation.
AB  - The experimental results of the direct measurement of the absolute value of
      interaction force between the fiber probe of a scanning near-field optical
      microscope (SNOM) operated in shear force mode and a sample, which were performed
      using combined SNOM-atomic force microscope setup, are discussed for the out-of
      resonance fiber probe excitation mode. We demonstrate that the value of the
      tapping component of the total force for this mode at typical dither amplitudes
      is of the order of 10 nN and thus is quite comparable with the value of this
      force for in resonance fiber probe excitation mode. It is also shown that for all
      modes this force component is essentially smaller than the usually neglected
      static attraction force, which is of the order of 200 nN. The true contact nature
      of the tip-sample interaction during the out of resonance mode is proven. From
      this, we conclude that such a detection mode is very promising for operation in
      liquids, where other modes encounter great difficulties.

PMID- 15149718
TI  - Simultaneous atomic-force and two-photon fluorescence imaging of biological
      specimens in vivo.
AB  - We describe in this paper a home-built scanning-probe setup that combines the
      high spatial resolution of a commercial atomic-force microscope (AFM) with the
      high sensitivity and the discriminative power of a confocal two-photon
      fluorescence microscope. This scheme offers the ability of acquiring
      simultaneous, directly correlated topography and optical images with high
      sensitivity and resolution, and was successfully tested using model systems, such
      as dye-loaded latex beads. As a first biological application, we studied the
      (un)stacking of grana membranes in the envelope-free plant chloroplasts. The
      topographs showed two grana layers attached together in a "native unit" 15-16 nm
      thick and 4 nm protrusions on their surface, which we assign to Photosystem II
      reaction center. The optical imaging did not resolve single photosynthetic
      proteins, but helped in identifying the grana and indicated that the protein
      conformation and the chromophore binding are intact. Furthermore, our instrument
      allowed a direct comparison between the cell morphology and the distribution of
      the signaling protein H-Ras in living cells, i.e. mouse fibroblasts. With our
      approach the nanometer-scale resolving power of AFM is improved with the chemical
      identification capabilities of optical techniques, thus opening up interesting
      possibilities in various areas of research, including material and life sciences.

PMID- 15149719
TI  - Low-voltage electron microscopy of polymer and organic molecular thin films.
AB  - We have demonstrated the capabilities of a novel low-voltage electron microscope
      (LVEM) for imaging polymer and organic molecular thin films. The LVEM can operate
      in transmission electron microscopy, scanning transmission electron microscopy,
      scanning electron microscopy, and electron diffraction modes. The microscope
      operates at a nominal accelerating voltage of 5 kV and fits on a tabletop. A
      detailed discussion of the electron-sample interaction processes is presented,
      and the mean free path for total electron scattering was calculated to be 15 nm
      for organic samples at 5 kV. The total end point dose for the destruction of
      crystallinity at 5 kV was estimated at 5 x 10(-4) and 3.5 x 10(-2) C/cm2 for
      polyethylene and pentacene, respectively. These values are significantly lower
      than those measured at voltages greater than 100 kV. A defocus series of
      colloidal gold particles allowed us to estimate the experimental contrast
      transfer function of the microscope. Images taken of several organic materials
      have shown high contrast for low atomic number elements and a resolution of 2.5
      nm. The materials studied here include thin films of the organic semiconductor
      pentacene, triblock copolymer films, single-molecule dendrimers, electrospun
      polymer fibers and gold nanoparticles.

PMID- 15149720
TI  - JECP/PCED--a computer program for simulation of polycrystalline electron
      diffraction pattern and phase identification.
AB  - A computer program for simulation of polycrystalline electron diffraction pattern
      and phase identification is described. In addition to simulating electron
      diffraction pattern for a single phase, the program has the ability to model two
      phases with selected mass ratio. Experimental polycrystalline electron
      diffraction patterns can be directly compared to simulated patterns for phase
      identification. Examples of how to use the program are also given.

PMID- 15149721
TI  - About GATA3, HNF3A, and XBP1, three genes co-expressed with the oestrogen
      receptor-alpha gene (ESR1) in breast cancer.
AB  - In breast tumours and breast cancer cell (BCC) lines, microarray analyses have
      revealed that a series of genes are expressed in close association with the
      oestrogen receptor-alpha (ER-alpha) gene, ESR1. Three of them, GATA3, HNF3A (also
      known as FOXA1), and XBP1 encode transcription factors. Here, we present these
      factors and we discuss their potential involvement in the ER-alpha-mediated
      actions in BCC. We notably show the relations that exist, or that might exist,
      between these factors and the oestrogen-inducible trefoil factor TFF1.

PMID- 15149722
TI  - Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese
      subjects.
AB  - Adiponectin is an adipocyte-specific protein suggested to play a role in
      mediating the metabolic effects of obesity. In the present study, we investigated
      adiponectin mRNA levels in both visceral and subcutaneous abdominal adipose
      tissue (AT) from lean and obese subjects. Investigations on both "fresh" fat
      biopsies and incubations of AT fragments were performed. Regional differences in
      the effects of the cytokine interleukin-1beta (IL-1beta) were investigated.
      Adiponectin gene expression was 33% lower in visceral AT than in subcutaneous AT
      of lean subjects (P < 0.05), and 28% lower in obese subjects, albeit non
      significant (P = 0.3). In both lean and obese subjects adiponectin mRNA
      expression in incubated AT fragments was significantly lower in visceral AT than
      in subcutaneous AT (lean: P < 0.01; obese: P < 0.05). No difference was found in
      adiponectin mRNA levels in gluteal compared to abdominal subcutaneous AT. IL
      1beta suppressed adiponectin mRNA levels substantially in both subcutaneous and
      visceral AT. In conclusion, adiponectin gene expression is lower in visceral AT
      than in subcutaneous abdominal AT, suggesting subcutaneous AT to be more
      important for circulating adiponectin levels.

PMID- 15149723
TI  - Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular
      smooth muscle cell proliferation by estrogens.
AB  - Estrogen has been postulated to exert direct anti-atherogenic effects via binding
      to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). Therefore,
      we believe it is important to examine the status of ER expression in the human
      cardiovascular system and its disorders. In this study, we first evaluated the
      relative abundance of messenger RNA (mRNA) of both ER subtypes (ERalpha and
      ERbeta) in the human aorta using reverse transcription followed by quantitative
      polymerase chain reaction (RT-qPCR). We then examined the immunolocalization of
      both ERs in VSMCs of human atherosclerotic lesions. In order to examine which ER
      subtype was associated with the anti-atherogenic effects of estrogen, we examined
      the effects of estrogen in two VSMC cell lines, one positive only for ERalpha and
      the other positive only for ERbeta. The relative abundance of mRNAs for both ERs
      was higher in female aorta with a mild degree of atherosclerosis than in female
      aorta with a severe degree of atherosclerosis (P < 0.05). In addition, the number
      of ERalpha and/or ERbeta double positive cells in the neointima was higher in
      female aorta with a mild degree of atherosclerosis than in female aorta with
      severe atherosclerosis (P < 0.05). Our in vitro study found that estradiol was
      able to significantly inhibit the proliferation of ERalpha positive VSMCs but not
      ERbeta positive VSMCs (P < 0.05). Moreover, estradiol was found to significantly
      suppress proliferating cell nuclear antigen (PCNA) mRNA levels in ERalpha
      positive VSMCs compared to that of ERbeta positive VSMCs, consistent with the
      findings of cell proliferation. Results from this study suggest that estrogens
      can inhibit the proliferation of VSMCs through ERalpha, especially in pre
      menopausal women. Our study also indicates that decreased levels of ER,
      especially ERalpha, in the female atherosclerotic neointima may be associated
      with progression of atherosclerotic changes.

PMID- 15149724
TI  - The effect of the new SERM arzoxifene on growth and gene expression in MCF-7
      breast cancer cells.
AB  - The benzothiophene arzoxifene is a new 3rd generation selective estrogen receptor
      (ER) modulator (SERM). We have investigated the effect of arzoxifene on growth
      and gene expression in the estrogen receptor alpha (ERalpha) positive human
      breast cancer cell line MCF-7. Arzoxifene inhibits cell growth as effectively as
      the antiestrogen tamoxifen. Northern analysis revealed that arzoxifene exerts a
      statistically significant inhibition of pS2 and progesterone receptor B mRNA
      expression. Significant agonistic effect was observed on the antitrypsin mRNA
      expression. In contrast to estradiol and tamoxifen, arzoxifene does not
      upregulate cathepsin D mRNA and protein expression. The metabolite of arzoxifene
      (ARZm) is a more potent growth inhibitor of MCF-7 cells than arzoxifene. A
      tamoxifen resistant MCF-7 subline displayed a significant dose-dependent growth
      inhibition to ARZm, whereas an ICI 182,780 resistant cell line only responded to
      high concentration. Our results indicate that arzoxifene and especially ARZm are
      efficient growth inhibitors of ER positive human breast cancer cells, including
      tamoxifen resistant cells. Moreover, arzoxifene displays less estrogen agonistic
      effects in MCF-7 cells than tamoxifen.

PMID- 15149725
TI  - DD-RT-PCR identifies 7-dehydrocholesterol reductase as a key marker of early
      Leydig cell steroidogenesis.
AB  - Postnatal Leydig cell development in rat involves an initial phase of
      proliferation of progenitor Leydig cells (PLCs) and subsequent differentiation of
      these cells into immature Leydig cells (ILCs) and adult Leydig cells (ALCs). With
      an objective to identify the molecular changes associated with Leydig cell
      differentiation, the mRNA population in PLCs and ILCs were analyzed by the
      technique of differential display reverse transcription polymerase chain reaction
      (DD-RT-PCR). Results revealed differential expression of several transcripts in
      PLCs and ILCs. Of the several differentially expressed transcripts, the
      expression of transcripts corresponding to collagen IV alpha6 (Col IV alpha6) and
      ribosomal protein L 41 (RpL41) decreased during the differentiation of PLC to
      ILC. Also there was an increase in the expression of transcripts encoding enzymes
      such as microsomal glutathione-S-transferase (mGST 1) and 7-dehydrocholesterol
      reductase (7-DHCR) during this process. While Col IV alpha6 and RpL41 are known
      to be involved in cellular proliferation, mGST 1 and 7-DHCR are essential for
      normal Leydig cell steroidogenesis. A detailed study on 7-DHCR expression in
      Leydig cells revealed that this enzyme plays a crucial role in steroidogenesis.
      Interestingly expression of this enzyme is not under acute regulation by
      Luteinizing hormone (LH).

PMID- 15149726
TI  - Pro7.33(303) of the human GnRH receptor regulates selective binding of mammalian
      GnRH.
AB  - Mammalian gonadotropin releasing hormone (GnRH) receptors have a conserved acidic
      residue (Glu7.32(301) or Asp7.32(302)) in extracellular loop (ECL) three that
      confers selectivity for mammalian GnRH, which has Arg8. Comparison of mammalian
      and non-mammalian GnRH receptors suggested that the acidic residue is not the
      only determinant of ligand selectivity in mammalian receptors. The acidic residue
      is followed by a conserved Pro7.33 in mammalian GnRH receptors, but not non
      mammalian receptors. Unique structural constraints imposed by Pro residues
      suggested that Pro7.33 determines selective binding of Arg8-containing GnRH, by
      stabilising the conformation of the third extracellular loop of the receptor.
      Substituting Pro7.33(303) or introducing Pro to position 7.31 decreased affinity
      for GnRH, but not analogs lacking Arg8. Substituting Pro7.33(303) changed the
      predicted alpha-helix content of the loop-helix interface. These results show
      that Pro7.33(303) of the human GnRH receptor is required for selective high
      affinity binding of mammalian GnRH and supports the hypothesis that Pro7.33(303)
      stabilises a loop conformation that is necessary for selective ligand binding.

PMID- 15149727
TI  - Expression of sex hormone-binding globulin (SHBG) in human granulosa-lutein
      cells.
AB  - Sex hormone-binding globulin (SHBG) was classically thought to be a plasma
      steroid-carrying protein of hepatic origin, but recently, locally produced,
      membrane-bound SHBG has been shown to influence cell functions in several steroid
      responsive tissues. In the ovary, SHBG is known to be present in the follicular
      fluid, but information about a possible intracellular presence of SHBG in this
      organ is still very scarce. In this study the presence of SHBG was assessed by
      immunohistochemistry in human granulosa-lutein cells (GLC) collected by follicle
      puncture for in vitro fertilization. SHBG was detected in the cytoplasm of GLC
      before and after in vitro culture for up to 96 h. The presence of full-length
      SHBG messenger RNA was demonstrated in GLC by reverse transcription-polymerase
      chain reaction (RT-PCR) in both cultured and uncultured cells. These results
      demonstrate a local synthesis of SHBG in GLC and raise the question of the
      physiological significance of these findings in follicular physiology.

PMID- 15149728
TI  - Hyper and hypothyroidism change the expression and diurnal variation of thyroid
      hormone receptor isoforms in rat liver without major changes in their zonal
      distribution.
AB  - We investigated the effect of hypothyroidism or hyperthyroidism on mRNA and
      protein expression, diurnal variation and zonal distribution of thyroid hormone
      receptor (TR) isoforms TRalpha1, TRalpha2 and TRbeta1 in rat liver.
      Hypothyroidism results in increased isoform mRNA and protein expression whereas
      hyperthyroidism shows a decreased TRalpha1 and TRalpha2 mRNA and protein
      expression. During hyperthyroidism no change is seen in TRbeta1 mRNA, but TRbeta1
      protein is upregulated in the light period and downregulated in the dark period.
      Diurnal changes (measured at 13:30 and 19:30 h) in the TR isoform proteins are
      abolished in hypothyroidism and hyperthyroidism, with the exception of a reversal
      in diurnal changes of TRbeta1 in hyperthyroidism. Zonal distribution of the
      isoforms is not affected by hypo- or hyperthyroidism. We therefore conclude that
      thyroid hormone influences both the levels and the diurnal expression of its
      receptor isoforms but not the zonal distribution.

PMID- 15149729
TI  - Alteration of beta-cell constitutive NO synthase activity is involved in the
      abnormal insulin response to arginine in a new rat model of type 2 diabetes.
AB  - We have previously obtained a new type 2 diabetic syndrome in adult rats given
      streptozotocin and nicotinamide, characterized by reduced beta-cell mass,
      partially preserved insulin response to glucose and tolbutamide and excessive
      responsiveness to arginine. We have also established that the neuronal isoform of
      constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin
      secretion. In this study, we explored the kinetics of glucose- and arginine
      stimulated insulin release in perifused isolated islets as well as the effect of
      N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight
      into the possible mechanisms responsible for the arginine hypersensitivity
      observed in vitro in this and other models of type 2 diabetes. A reduced first
      phase and a blunted second phase of insulin secretion were observed upon glucose
      stimulation of diabetic islets, confirming previous data in the isolated perfused
      rat pancreas. Exposure of diabetic islets to 10 mM arginine, in the presence of
      2.8 mM glucose, elicited a remarkable monophasic increment in insulin release,
      which peaked at 639 +/- 31 pg/islet/min as compared to 49 +/- 18 pg/islet/min in
      control islets (P << 0.01). The addition of L-NAME to control islets markedly
      enhanced the insulin response to arginine, as expected from the documented
      inhibitory effect exerted by nNOS activity in normal beta-cells, whereas it did
      not further modify the insulin secretion in diabetic islets, thus implying the
      occurrence of a defective nNOS activity in these islets. A reduced expression of
      nNOS mRNA was found in the majority but not in all diabetic islet preparations
      and therefore cannot totally account for the absence of L-NAME effect, that might
      also be ascribed to post-transcriptional mechanisms impairing nNOS catalytic
      activity. In conclusion, our results provide for the first time evidence that
      functional abnormalities of type 2 experimental diabetes, such as the insulin
      hyper-responsiveness to arginine, could be due to an impairment of nNOS
      expression and/or activity in beta-cells.

PMID- 15149730
TI  - Cloning, sequence analysis, tissue distribution, and sex-specific expression of
      the neural form of P450 aromatase in juvenile sea bass (Dicentrarchus labrax).
AB  - The teleost brain is characterized by exceptionally high levels of aromatase, the
      enzyme that converts androgens into estrogens, and by its continuous growth
      throughout life. Gonadal estrogens have been implicated in sex differentiation
      and the control of reproduction in adult fish, but the role of neural estrogens
      during early development is far from clear. The present study describes the
      isolation and characterization of the cDNA sequence from brain aromatase
      (P450aromB) in the European sea bass (Dicentrarchus labrax L.), a well
      established model for neuroendocrine research in fish. P450aromB was cloned from
      a brain cDNA library and encoded a predicted protein of 505 residues, with a
      calculated molecular weight of 57.2 kDa. Comparisons of the deduced amino acid
      sequence to that of the ovarian aromatase (P450aromA) in the same species
      revealed 62% identity, lower than the 84% identity shared between sea bass and
      tilapia brain aromatases. Phylogenetic analysis showed the occurrence of a gene
      duplication for P450arom in the teleost lineage after its divergence from the
      tetrapods. Moreover, the low percentage of identity between brain and ovarian
      forms within the same species suggests that both genes evolved separately right
      after the appearance of the teleosts. Tissue-specific expression of P450aromA and
      P450aromB mRNA was studied in adult sea bass. P450aromB was preferentially
      expressed in brain of both males and females but also present at much lower
      levels in testis, ovary and head kidney, an organ known for its steroidogenic
      capabilities in fish. However, P450aromA expression was restricted to testis and
      ovary. A semiquantitative PCR was developed to measure P450aromB mRNA levels.
      Analysis of the expression of P450aromB in the brain of juvenile sea bass showed
      that females exhibited higher mRNA levels than males at 200 days post
      fertilization (dpf), by the time of gonadal sex differentiation. A switch in
      expression occurred thereafter, between 200 and 250 dpf, with males exhibiting
      higher levels than females. This situation was maintained by 300 dpf and is in
      agreement with measured levels of enzymatic activity in adults. These changes and
      sex-related differences in expression profiles may imply differences in the
      functionality of the enzyme between males and females, suggesting an important
      role for P450aromB in sea bass sex differentiation. However, due to the
      continuous growth of the teleost brain throughout life, a role in neurogenesis
      for brain aromatase should also be considered.

PMID- 15149731
TI  - A molecular basis for embryo apposition at the luminal epithelium.
AB  - To obtain a gene expression profile during embryo apposition to the luminal
      epithelium, we isolated mouse luminal epithelium from implantation (IM) and
      interimplantation (INTER) sites using laser capture microdissection (LCM), and
      analyzed their gene expression by microarray analysis. IM and INTER sites were
      sampled on day 4.5 after mating of female mice with fertile males (day 0.5 =
      vaginal plug). RNA was extracted, amplified, labeled, and hybridized to
      microarrays and results were analyzed using the significance analysis of
      microarrays (SAM) method. Comparison of IM and INTER sites by SAM identified 73
      genes most highly ranked at IM, while 13 genes most highly expressed at the INTER
      sites, within the estimated false discovery rate (FDR) of 0.163. Among 73 genes
      at IM, 20 were ESTs or were of unknown function, and the remain 53 genes had
      known functions mainly relating to cellular structuring and others such as cell
      cycling, gene/protein expression, immune responses, invasion, metabolism,
      oxidative stress, or signal transduction. Specifically, of the 24 structural
      genes, 14 were implicated in extracellular matrix and tissue remodeling.
      Meanwhile, of the 13 genes that were highly expressed at INTER, eight were ESTs
      or of unknown function, and the remaining five were implicated in metabolism,
      signal transduction, and gene/protein expression. Among these 58 (53 + 5) genes
      with known functions, 13 genes (22.4%) were associated with Ca2+ for their
      function. Results of the present study suggest that (1) at IM sites, active
      tissue remodeling is occurring for embryo invasion while the INTER sites are
      relatively quiescent and (2) Ca2+ may be a vital regulatory factor in the
      apposition process. Investigations of human homologues of those genes expressed
      in the mouse luminal epithelium during apposition may help to understand the
      implantation process and/or implantation failure in humans.

PMID- 15149732
TI  - Gene expression phenotyping of an ACTH-producing small cell lung cancer line.
AB  - DNA microarray techniques were used to compare gene expression in an
      adrenocorticotropin (ACTH)-producing human small cell lung carcinoma line (DMS
      79) with six other small cell lung cancer (SCLC) lines that do not produce ACTH.
      Twelve genes were expressed at more than five-fold higher levels in DMS-79 cells.
      Two transcription factors were the genes that exhibited the most remarkable over
      expression: T-box 3 mRNA was detected at levels 19.37 +/- 3.78 times those
      observed in the SCLCs. Thyroid transcription factor (TTF-1, T/ebp, Nkx2.1) was
      expressed at 14.24 +/- 3.41-fold higher in DMS-79 cells. Seven genes were
      identified whose expression levels were at least five-fold lower in the ACTH
      producing cell line. Variation in culture medium formulation did not
      significantly affect the gene expression profile of DMS-79 cells and expression
      data observed in microarray experiments were corroborated by northern blot
      analysis of RNA from the same cell lines. These experiments reveal new candidate
      genes that could be involved in the dysregulation of POMC gene expression
      manifested by ACTH-producing nonpituitary tumors.

PMID- 15149733
TI  - Regulation of the human relaxin genes H1 and H2 by steroid hormones.
AB  - Relaxin, a peptide hormone important to the outcome of human pregnancy is
      expressed in a tissue specific manner as two genes known as relaxins H1 and H2,
      in addition to a third human relaxin H3, expressed primarily in the brain. The H1
      and H2 genes are highly homologous, differentially expressed in reproductive
      tissues and appear to activate the same receptor, but their regulation is poorly
      understood. Based upon the known physiology of these hormones and the response
      elements in their 5'- and 3'-flanking regions, the possibility that progesterone
      and/or the glucocorticoids might influence their differential expression was
      therefore investigated. The changes in the mRNA levels of the relaxin genes in
      response to either medroxyprogesterone acetate (MPA) or dexamethasone (Dex) were
      analyzed by RT-PCR using a choriocarcinoma cell line (JAR) as a model system,
      because the expression of these genes in any primary human cell type is too low
      for such a study. The addition of 0.5 microM MPA to JAR cells, significantly
      upregulated the mRNA of only the relaxin H2, while the addition of 0.5 microM Dex
      significantly upregulated the mRNAs for both the relaxins, after 6h of treatment.
      Promoter assays indicated an early activation of transcription (1 h), which by 6
      h had decreased. Progesterone and/or glucocorticoids could exert their effects
      via the GRE motif found on the 5'-flanking region of the relaxin genes. The H1
      GRE differs from the H2-GRE by a single nucleotide, which may affect H1-GRE
      binding to the progesterone receptor (PR) but not the glucocorticoid receptor
      (GR). The antiprogestin RU486 inhibited the binding of the GR to both H1-GRE and
      H2-GRE, while it enhanced the binding of the PR to these GREs. As determined by
      gel shift assays, this GRE motif could bind to both the PR and GR and was
      therefore considered to be functional. Thus, both progesterone and
      glucocorticoids are capable of differentially regulating the expression of the
      two human relaxin genes in a model system.

PMID- 15149734
TI  - Selective estrogen receptor modulator regulated proteins in endometrial cancer
      cells.
AB  - Tamoxifen is the primary hormonal therapy for breast cancer and is also used as a
      breast cancer chemopreventative agent. A major problem with tamoxifen therapy is
      undesirable endometrial proliferation. To identify proteins associated with the
      growth stimulatory effects of tamoxifen in an ER-positive model, the present
      study profiled total cellular and secreted proteins regulated by estradiol and
      selective estrogen receptor modifiers (SERMs) in the Ishikawa endometrial
      adenocarcinoma cell line using two-dimensional gel electrophoresis. Following 24
      h incubation with 10(-8) M estradiol, 10(-7) M 4-hydroxytamoxifen, or 10(-7) M EM
      652 (Acolbifene), nine proteins exhibited significant increase in expression. The
      proteins identified were heat shock protein 90-alpha, and -beta, heterogeneous
      nuclear ribonucleoprotein F, RNA polymerase II-mediating protein, cytoskeletal
      keratin 8, cytoskeletal keratin 18, ubiquitin-conjugating enzyme E2-18 kDa and
      nucleoside diphosphate kinase B. These protein profiles may serve as novel
      indices of SERM response and may also provide insight into novel mechanisms of
      SERM-mediated growth.

PMID- 15149735
TI  - Cyclic adenosine 3',5'-monosphosphate mediate prolactin regulation of
      mitochondrial aconitase in human prostate carcinoma cells.
AB  - Mitochondrial aconitase (mACON) is regarded as the key enzyme for citrate
      oxidation in human prostatic epithelial cells. The results of RT-PCR and
      immunoblot assays indicated that human prostatic carcinoma cells (PC-3 cells)
      express the long-form of the prolactin receptor. In vitro studies determined that
      prolactin upregulates mACON enzymatic activity and cell proliferation of PC-3
      cells. Immunoblot assay revealed that prolactin treatments increase the gene
      expression of mACON. Transient gene expression assay indicated that the
      regulation by prolactin of mACON gene expression depends on the presence of the
      cyclic adenosine 3',5'-monosphosphate (cAMP) response element on the promoter of
      the mACON gene. Both prolactin and dibutyryl-cAMP doubled the promoter activity
      of the mACON gene; however, adding H-89, a specific protein kinase A inhibitor,
      suppressed the prolactin response. The intracellular cAMP levels, but not the
      cGMP levels, increased after treatment with prolactin. This study showed that
      prolactin regulates the expression of the mACON gene via the cAMP signal pathway
      in human prostatic carcinoma cells.

PMID- 15149736
TI  - Requirements for transcriptional regulation by the orphan nuclear receptor
      ERRgamma.
AB  - Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor lacking
      identified natural ligands. We have addressed the requirements for ERRgamma
      mediated gene regulation. ERRgamma transactivates constitutively reporter genes
      driven by ERR response elements (ERREs) or estrogen response elements (EREs). The
      activation depends on an intact DNA-binding domain (DBD) and activation function
      2 (AF2). ERRgamma-mediated transactivation is further enhanced by peroxisome
      proliferator-activated receptor coactivator-1. Interestingly, ligand-binding
      domain (LBD) mutations predicted to either enlarge or diminish the putative
      ligand-binding pocket have no effect on the transcriptional activity implying
      that ERRgamma activity does not depend on any ligands. Antiestrogens 4OH
      tamoxifen (4OHT) and 4-hydroxytoremifene (4OHtor) inhibit the ability of ERR to
      transactivate ERRE and ERE reporters. In contrast, ERRgamma activates
      transcription at AP-1 sites in the presence of 4OHT and 4OHtor. Thus, the
      transcriptional activity of ERRgamma seems not to require ligand binding but is
      modulated by binding of certain small synthetic ligands.

PMID- 15149738
TI  - Genistein alters growth factor signaling in transgenic prostate model (TRAMP).
AB  - Genistein, a component of soy, has been reported to protect against spontaneously
      developing prostate tumors in the transgenic adenocarcinoma of mouse prostate
      (TRAMP) model. This is consistent with reports showing that Asians eating a diet
      high in soy have reduced incidence of clinically manifested prostate cancer. In
      order to understand the mechanism of action of genistein, we have investigated
      the expression of androgen and estrogen receptors, four growth factor receptors
      that signal via tyrosine protein kinases, and specific growth factor proteins in
      the dorsolateral prostates of TRAMP mice fed 250 mg genistein/kg diet, starting
      at 5 weeks of age. These analyses were carried out at 12 weeks, prior to the
      development of solid tumors, allowing us to readily investigate cell
      proliferation and biomarkers in premalignant tissue. Cell proliferation, AR, ER
      alpha, EGFR, ErbB2, EGF, IGF-1R, IGF-1, VEGFR2, ERKs-1 and 2 proteins and TGF
      alpha mRNA, but not ER-beta and VEGF, were significantly increased in prostates
      of TRAMP compared to C57BL/6 mice. Genistein in the diet significantly down
      regulated cell proliferation, EGFR, IGF-1R, ERK-1 and ERK-2, but not AR, ER
      alpha, ER-beta, ErbB2, EGF, TGF-alpha, IGF-1, VEGF and VEGFR in prostates of
      TRAMP mice. Serum testosterone and dihydrotestosterone concentrations were not
      significantly different in C57BL/6 or TRAMP male mice fed control or genistein
      containing diets. The up-regulation of sex steroid receptors and multiple growth
      signaling pathways in TRAMP mice supports the concept of multiple dysregulation
      contributing to carcinogenesis. Down-regulation of the tyrosine kinase regulated
      proteins, EGFR and IGF-1R, and of the downstream mitogen-activated protein
      kinases, ERK-1 and 2, with genistein in the diet provides a possible mechanism
      for prostate cancer chemoprevention.

PMID- 15149737
TI  - Cyclic adenosine monophosphate (cAMP) increases natriuretic peptide receptor C
      (NPR-C) expression in human aortic smooth muscle cells.
AB  - Activation of the intracellular cAMP-signaling pathway by either forskolin or the
      cAMP-mimetic dibutyryl cAMP significantly increased transcript levels of NPR-C in
      primary cultures of human aortic smooth muscle cells. The time course of the
      increase was rapid, with significant differences from control occurring within 3
      h of treatment and reaching approximately 6 times control value after 24 h of
      exposure to 10 microM forskolin. Expression levels of the natriuretic peptide
      receptor B (NPR-B), but not the natriruetic peptide receptor A (NPR-A) were also
      increased by forskolin, rising to a level of approximately 2 times control at 96
      h. NPR-B transcript levels in the presence of dibutyryl cAMP were unaltered by
      the protein kinase A (PKA) inhibitor KT-5720, suggesting a PKA-independent
      pathway to NPR-B up-regulation. In contrast, KT-5720 reduced NPR-C transcript to
      a lower level that was not significantly different from control. Partial re
      differentiation of AOSMC by culture in growth factor-reduced matrix (Matrigel)
      did not significantly change NPR-C transcript levels compared with cells grown on
      plastic, and the dibutyryl cAMP-induced increase in NPR-C (approximately eight
      nine-fold control value) was retained. The dibutyryl cAMP/forskolin effect on NPR
      C transcript was not reproduced by the beta2-selective adrenergic agonist
      isoproterenol (10 microM), but was replicated by incubation with the
      phosphodiesterase inhibitor isobutylmethylxanthine (0.5 mM). Up-regulated NPR-B
      and NPR-C transcript levels were reflected, respectively, in a two-fold increase
      in CNP-stimulated cGMP and an increase in 125I-ANF binding competed by the NPR-C
      specific natriuretic peptide, C-ANF(4-23) following a 4-day treatment with 0.125
      mM dbcAMP. The present data suggest that elevation of cAMP in human vascular
      smooth muscle may potentiate the vasoactive effects of natriuretic peptides
      acting through the NPR-B and NPR-C receptors.

PMID- 15149739
TI  - Molecular mechanisms of prostate cancer.
AB  - During the last ten years our knowledge of genetic alterations in prostate cancer
      has significantly increased. For example, several chromosomal loci possibly
      harboring predisposing or somatically mutated genes have been suggested. Still,
      we lack the comprehensive molecular model for the development and progression of
      prostate cancer. Only a few genes have been found to be aberrant in a significant
      proportion of prostate cancer. These include GSTP1, PTEN, TP53, and AR. Thus,
      they are natural targets for new treatment strategies.

PMID- 15149740
TI  - Changing concepts in the surgical management of renal cell carcinoma.
AB  - The foundations of the generally accepted principles underlying the surgical
      management of renal cell carcinoma (RCC) were best annunciated in 1969 by Robson
      in his classic description of the radical nephrectomy [J Urol 1969;101;297].
      Since then, much has changed in our understanding of the basic biology and
      genetics of kidney cancer, advances in renal imaging and clinical staging have
      led to the increased detection of incidental, lower stage, organ-confined tumors
      more amendable to expanded surgical options, surgical techniques themselves have
      evolved, and surgical equipment technology has advanced to make possible new
      methods of managing renal tumors in situ. Thus, the management of both localized
      and metastatic RCC has changed dramatically in the last 20 years, predicated on
      these major advancements in renal imaging, surgical techniques, and the
      development of effective immunotherapies for advanced disease. In this review,
      the evolution in thinking regarding the tenets of the radical nephrectomy will be
      examined, including the necessity for removal of the entire kidney, the
      possibility of sparing the adrenal gland, when and how extensive a
      lymphadenectomy should be performed, the development of laparoscopic and
      percutaneous nephron-sparing surgery using ablative technologies, and the role of
      nephrectomy and metastasectomy in patients with metastatic RCC. Here, we review
      current concepts and outcomes on the surgical management of RCC to help elucidate
      some of these changes, from the evolution of open to laparoscopic to
      percutaneous, from radical to partial to ablative approaches.

PMID- 15149741
TI  - Melanocortin receptors and erectile function.
AB  - OBJECTIVE: Review the historical and current evidence that suggests that
      activation of melanocortin receptors modulates erectile activity. METHODS: The
      available literature was reviewed. RESULTS: Melanocortin peptides derived from
      the pro-opiomelanocortin (POMC) precursor protein exert a host of diverse
      physiological effects in the periphery and in the CNS through interactions with
      one or more of the five cloned melanocortin receptors. Natural and synthetic
      melanocortin peptide agonists influence erectile and sexual function in a range
      of preclinical species. Emerging clinical evidence now suggests that the
      proerectile effects observed in preclinical species are evident in man as well.
      CONCLUSIONS: Preclinical and clinical results support the involvement of
      melanocortins in the modulation of erectile and sexual function. Current evidence
      indicates that the melanocortin 4 receptor subtype contributes to the proerectile
      effects observed with pan-receptor agonists. However, the putative receptor
      subtypes, pathways and mechanisms implicated in mediating the proerectile effects
      of melanocortins remain to be fully elucidated.

PMID- 15149742
TI  - Management of ureteric stones.
AB  - The contemporary management of ureteric stones is reviewed and evidence based
      recommendations about treatment are made. Stones measuring less than 4mm in
      diameter have a high chance of spontaneous passage and the main debate for
      optimum treatment of larger stones centres around the choice of shock wave
      lithotripsy or endoscopic management combined with laser fragmentation. Treatment
      recommendations should be based on patient preference, published evidence, local
      audit (surgeon expertise and availability of equipment) and cost. Artificial
      Neural Networks could become a useful tool for prediction of treatment outcome
      for ureteric stones, and further research is needed to clarify this potential.
      ESWL is less effective than ureteroscopy but it may prevent the need for more
      invasive treatment in a substantial proportion of patients. It should only be
      considered as initial treatment in patients with stones less than 10mm in size.
      The routine use of stents should be avoided as both fragmentation and stone free
      rates are noticeably lower. For larger stones, initial laser ureteroscopy serves
      better both for proximal or distal calculi and is more cost-efficient. Provided
      that no contraindications for general anaesthesia exist, laser ureterolithotripsy
      should be regarded as an excellent first line treatment modality for ureteric
      stone especially in greater stone burden. In the best hands, the outcome for
      endoscopic management of ureteric stone in all sites is better than ESWL and is
      cheaper, although equipment, expertise and experience are all required to achieve
      this superior outcome.

PMID- 15149743
TI  - Handling and pathology reporting of adrenal gland specimens.
AB  - Proper treatment of resection specimens by the urologist and pathologist is
      critical in accurately reporting tumors and tumor-like nodules of the adrenal
      gland. Clinically inapparent adrenal masses are discovered, with increasing
      frequency, in the course of diagnostic testing or treatment for conditions that
      are not related to adrenal diseases. As a consequence an increasing number of
      relatively small tumors lacking the characteristic gross features of malignancy
      is detected. There is a need for identification of pathological findings that can
      improve the diagnostic accuracy and predict patient outcome. The aim of this
      paper is to review the handling and pathology reporting of adrenal gland
      specimens in the light of recent advances in this field of pathology.

PMID- 15149744
TI  - TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence,
      progression and survival in 137 selected patients followed up to 20 years.
AB  - OBJECTIVES: To evaluate a highly selected population of patients affected by T1G3
      bladder transitional cell carcinoma (TCCB) treated by transurethral resection
      (TUR) and adjuvant intravesical chemotherapy. MATERIALS AND METHODS: Between
      January 1976 and April 1999, 137 patients with T1G3 TCCB were treated by TUR plus
      intravesical chemotherapy. Particularly, a sequential combination of mitomycin C
      (MMC) and epirubicin (EPI) was adopted in 91 patients (66.4%). The main exclusion
      criteria were concomitant or previous Tis, previous T1G3 TCCB, tumor size greater
      than 3 centimeters and number of tumors more than 3. TUR was repeated if a
      superficial tumor recurred. Patients went off study if Tis, recurrent T1G3 or
      invasive tumor were detected during treatment or thereafter. Adjuvant therapy,
      recurrence and progression were considered in multivariate analysis regarding
      recurrence, progression and survival respectively. RESULTS: Observation period
      was up to 240 months with a minimum of 2 years in 112 patients (82%). Seventy
      patients (51%) recurred. The recurring tumor was again a T1G3 in 22 (16%)
      patients. Thirteen patients (9.5%) progressed. The 5-year progression-free
      survival rate was 90%. Median progression-free survival was 149 months. Twenty
      two patients (16%) died, 9 (6.6%) of whom due to bladder cancer. Median overall
      survival was 155 months. The 3- and 5-year disease-free overall survival rates
      were 89% and 80% respectively. Ten cystectomies (7.3%) were performed. In
      conclusion, 123 patients (90%) maintained their intact bladder with a mean
      disease-free overall survival of 104 months. The sequential combination of MMC
      and EPI adjuvant therapy resulted more effective to be than single drug
      chemotherapy on recurrence rate (p=0.0021) but had no impact upon progression
      (p=0.127) and specific survival (p=0.163). Progression (p<0.001) after
      conservative treatment was the main prognostic factor for survival. CONCLUSION: A
      conservative approach is an appropriate therapeutic option for the initial
      management of selected T1G3 bladder tumors.

PMID- 15149745
TI  - Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with
      tumor angiogenesis and prognosis.
AB  - OBJECTIVES: Maspin is a member of the serpin (serine protease inhibitor) family
      and has been shown to be a suppressor of tumor growth and an inhibitor of
      angiogenesis as well as metastasis in several types of tumors. We studied
      expression patterns of Maspin in pTa/pT1 urothelial carcinoma of the bladder and
      compared them with microvessel density (MVD) for two vascular markers (CD34 and
      CD105) and correlated the findings with clinical outcome. MATERIAL AND METHODS:
      We investigated tumor samples of 110 patients undergoing transurethral resection
      for pTa/pT1 bladder carcinoma (pTa, n=84; pT1, n=26; grade 1, n= 22; grade 2, n=
      81; grade 3, n=7). Immunohistochemical studies were performed using the
      monoclonal antibodies, anti-human Maspin (NCL Maspin), anti-CD34 Class II and
      anti-CD105. Maspin expression level was classified according to the staining
      intensity (- to +++). The blood vessels (CD34) and specifically proliferating
      blood vessels (CD105) were counted as vessels per field (microvessel density,
      MVD). RESULTS: Of the 110 tumors, 27 showed a negative immunostaining for Maspin,
      46 tumors stained +, 29 stained ++, and 8 stained +++. Maspin expression
      correlated inversely with CD34 reactivity. In tumors with loss of or only weak
      Maspin expression, the MVD for CD34 was 21.7 vessels per field, and 4.2 vessels
      per field for proliferating vessels (CD105), whereas Maspin-positive tumors had
      an MVD of 17.7 vessels per field (CD34), and of 6.0 vessels per field (CD105).
      Complete follow-up data are available in 92 patients. After a median follow-up of
      25 months, 18 of the 92 patients (19.6%) had tumor recurrences. Tumors with
      decreased Maspin expression (-/+) had a shorter disease-free interval (23 months)
      than patients with stronger Maspin (++/+++) expression (29 months), whereas a
      Kaplan-Meier analysis and the log-rank test showed no significant difference in
      disease-free survival between the patients. CONCLUSION: The clinical importance
      of Maspin has been mainly investigated regarding tumor progression or metastasis.
      We found a decreased Maspin expression in a large portion of pTa/pT1 bladder
      tumors. Even if patients with decreased Maspin expression have a slightly shorter
      disease-free survival Maspin does not appear to be a promising prognostic marker.

PMID- 15149746
TI  - Laparoscopic partial nephrectomy using microwave tissue coagulator for small
      renal tumors: usefulness and complications.
AB  - OBJECTIVES: We evaluated the usefulness and complications of laparoscopic partial
      nephrectomy for small renal tumors using a microwave tissue coagulator without
      renal pedicle clamping. METHODS: Between September 1999 and March 2003, 19
      patients with small renal tumors 11 to 45 mm in diameter underwent laparoscopic
      partial nephrectomy without renal ischemia. RESULTS: Six and 13 patients were
      treated by the transperitoneal and retroperitoneal approaches, respectively.
      Excluding a case with open conversion due to dense perirenal adhesions, 18
      patients successfully underwent laparoscopic procedures. The mean operative time
      was 240 minutes with minimal blood loss in 14 patients and 100 to 400 ml in 4. In
      a patient, frozen sections revealed a positive surgical margin and additional
      resection was performed. Postoperative complications included extended urine
      leakage for 14 days, arteriovenous fistula and almost total loss of renal
      function, respectively, in a patient. With the median follow-up of 19 months, no
      patients showed local recurrence or distant metastasis by CT scan. CONCLUSIONS:
      Laparoscopic non-ischemic partial nephrectomy using a microwave tissue coagulator
      may be useful for treating small renal tumors because it does not require
      advanced laparoscopic skill. However, the indication of this procedure should be
      highly selective in order to minimize serious complications secondary to
      unexpected collateral damage to surrounding structures.

PMID- 15149747
TI  - Prognostic value of multifocality on progression and survival in localized renal
      cell carcinoma.
AB  - OBJECTIVE: Incidence of multifocality in Renal Cell Carcinoma (RCC) is estimated
      at between 5 and 25%. Multifocality has been largely studied because of the
      growing interest in conservative surgery which is a risk of local recurrence. The
      aim of this study is to evaluate the relationship between multifocality and other
      prognostic parameters and whether it is an independent prognostic factor.
      MATERIAL AND METHODS: From 1980 to 1990, 255 patients (median age: 60.9 years)
      were treated by radical nephrectomy for pT1 to pT3b N0M0 RCC. The median follow
      up time was 183 months. Multifocality was defined as the existence of at least
      one other tumoral localization, macroscopically and microscopically diagnosed as
      renal cell carcinoma, in the same kidney. Studied parameters were: age, sex,
      side, size, stage, Fuhrman's grade, capsular invasion, renal vein involvement and
      microvascular invasion. Survival was assessed with Kaplan-Meier and Cox models.
      RESULTS: 37 cases of multifocal RCC were diagnosed (14.5%). There was only a
      significant correlation with stage (p=0.002) and with capsular invasion
      (p=0.002). No other factor was correlated with multifocality. It had no influence
      on the risk of metastatic progression, overall or specific survival. CONCLUSION:
      There is a significant correlation between capsular invasion and multifocality
      that has to be considered before proposing conservative surgery for a localized
      RCC. Multifocality has no influence on survival or metastatic progression in case
      of radical nephrectomy.

PMID- 15149748
TI  - Stage II testicular seminoma: patterns of recurrence and outcome of treatment.
AB  - OBJECTIVES: To review treatment outcome and patterns of failure for patients with
      stage II testicular seminoma and to identify prognostic factors for relapse.
      METHODS: From 1981 to 1999, 126 men with stage II seminoma were treated at
      Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and
      31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for
      prognostic significance for subsequent relapse. RESULTS: At median follow-up of
      8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year
      cause-specific survival were both 94% and the 5- and 10-year relapse-free rates
      were both 85%. Patients with stage IIA and IIB disease treated with RT and stage
      IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and
      83.3%, respectively. Seventeen percent of patients treated with radiotherapy and
      6% of those treated with chemotherapy have relapsed. Of the RT patients the
      commonest sites of relapse were left supraclavicular fossa, lung/mediastinum,
      bone, para-aortics and liver; nine patients had a solitary site of relapse. Two
      patients treated with chemotherapy had recurrence in the para-aortic and iliac
      nodes. For RT patients, larger primary tumour size was associated with a
      reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion
      were found not to be of prognostic significance. CONCLUSIONS: In stage IIA/B
      seminoma, radiotherapy continues to provide excellent results, as the majority of
      patients will be cured with this treatment alone. Chemotherapy is the treatment
      of choice for stage IIC seminoma.

PMID- 15149749
TI  - Morbidity of inguinal lymphadenectomy for invasive penile carcinoma.
AB  - OBJECTIVE: To determine the incidence and the consequences of complications
      related to modified and radical inguinal lymphadenectomy in patients with
      invasive penile carcinoma, defined by invasion of the corpus spongiosum or
      cavernosum (> or =T2). MATERIALS AND METHODS: A total of 118 modified (67.0%),
      and 58 radical (33.0%) inguinal lymphadenectomy were performed in 88 patients
      between 1989 and 2000. To decrease the morbidity, radical inguinal
      lymphadenectomy was proposed only in patients with palpable inguinal lymph nodes,
      uni- or bilaterally (N1 or N2). Modified inguinal lymphadenectomy was performed
      bilaterally in patients with invasive penile carcinoma and non-palpable inguinal
      lymph nodes (N0), and unilaterally in the side without inguinal metastases in N1
      patients. Complications were assessed retrospectively with a median follow-up of
      46 months and classified as early (event observed during the 30 days after the
      procedure) or late (event present after hospitalisation or after the first
      months). RESULTS: A total of 74 complications after 176 procedures were recorded.
      After modified inguinal lymphadenectomy, 8 early (6.8%) and 4 late (3.4%)
      complications were observed. There were a total of 110 dissections with no
      complications and 8 dissections with 1 or 2 complications. After radical inguinal
      lymphadenectomy, the morbidity increased with 24 early (41.4%) and 25 late
      (43.1%) complications, observed in only 18 of 58 radical procedures. Leg oedema
      was the most common late complication, interfering with ambulation in 13 cases
      (22.4%). CONCLUSION: Modified inguinal lymphadenectomy, with saphenous vein
      sparing and limited dissection offers excellent functional outcome in patients
      with invasive penile carcinoma and nonpalpable inguinal lymph nodes. The
      morbidity after radical lymphadenectomy still significant, especially in patients
      with multiple or bilateral superficial inguinal lymph nodes treated by pelvic and
      bilateral inguinal lymphadenectomy.

PMID- 15149750
TI  - The relation of lower urinary tract symptoms with life-style factors and
      objective measures of benign prostatic enlargement and obstruction: an Italian
      survey.
AB  - OBJECTIVES: The association between the severity of LUTS and prostate volume,
      prostate-related variables and general life-style factors was investigated in a
      large number of patients with persistent LUTS suggestive of BPH (LUTS/BPH).
      METHODS: Patients with LUTS/BPH aged between 50 and 80 years, were enrolled in
      this Italian, multicentre, observational study. The total, storage and voiding I
      PSS and I-PSS-QoL index were collected, prostate volume and urodynamic variables
      measured. Multiple logistic regression equations were used to obtain the odds
      ratio (and 95% confidence interval) of moderate plus severe I-PSS (>7) versus
      mild I-PSS (< or =7, reference category), with allowance for age stratification,
      whenever indicated. RESULTS: In total, 802 patients were evaluated. The strongest
      association was found between the total I-PSS and the QoL. There was a slightly
      increased risk to suffer from more severe LUTS with increasing age. A significant
      increase risk of developing storage symptoms was found in older patient cohorts.
      Decrease of Q(max) values, increase of Abrams-Griffith number, serum PSA levels
      and prostate volume as judged by digital rectal examination were significantly
      associated to a higher risk of developing LUTS. No association was found between
      symptom severity and prostate volume or post-voiding residual, estimated by
      ultrasound. CONCLUSIONS: No significant association between severity of LUTS and
      life-style factors was observed. An increased risk of developing LUTS was found
      in patients with lower maximum flow rate and in those with higher PSA values. The
      association between LUTS and prostate volume remains questionable.

PMID- 15149751
TI  - Evaluation of the clinical benefit of permixon and tamsulosin in severe BPH
      patients-PERMAL study subset analysis.
AB  - OBJECTIVE: To compare the efficacy of the lipido-sterolic extract of Serenoa
      repens, Permixon, to that of the alpha-blocker, tamsulosin, in the treatment of
      severe low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH).
      METHODS: In a 12-month, double-blind, randomized study that showed equivalent
      efficacy of Permixon 320 mg/day and tamsulosin 0.4 mg/day ("PERMAL study"), 685
      BPH patients with IPSS > or =10 had been analyzed for efficacy. Of these, the 124
      patients with severe LUTS (IPSS >19) at randomization were retained for this
      subset analysis. After a 4-week run-in period, 59 and 65 patients had been
      randomized to tamsulosin and Permixon groups, respectively. Both treatment groups
      were compared regarding the evolution from baseline of total IPSS and its
      irritative and obstructive subscores, LUTS-related QoL, prostate volume, Q(max)
      and MSF-4 (sexual activity questionnaire) at different time points over 1 year.
      An analysis of variance of changes from baseline to end point was performed for
      all the parameters. The over-time evolutions of total, irritative and obstructive
      IPSS were further compared using a variance analysis for repeated measurements.
      RESULTS: At 12 months, total IPSS decreased by 7.8 with Permixon and 5.8 with
      tamsulosin (p=0.051); the irritative symptoms improved significantly more
      (p=0.049) with Permixon (-2.9 versus -1.9 with tamsulosin). The superiority of
      Permixon in reducing irritative symptoms appeared as soon as month 3 and was
      maintained up to month 12 (p=0.03). CONCLUSION: Permixon 320 mg/day was shown to
      be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH
      patients after 3 months and up to 12 months of treatment.

PMID- 15149752
TI  - Functional tissue engineering of autologous tunica albuginea: a possible graft
      for Peyronie's disease surgery.
AB  - OBJECTIVES: The aim of the present study was to generate a tissue engineered type
      of mechanically stable graft suitable for surgical replacement of the tunica
      albuginea penis. METHODS: Porcine fibroblasts isolated from open fascia biopsies
      were seeded on decellularized collagen matrices and then cultivated in a
      bioreactor under continuous multiaxial stress for up to 21 days (n=12). Static
      cultures without mechanical stress served as controls. Cell proliferation, cell
      alignment, and de novo synthesis of extracellular matrix proteins (proteoglycans,
      procollagen I, elastin) in these grafts was evaluated by hematoxylin-eosin,
      pentachrome, and immuno-staining. Additionally, the enzymatic isolation of
      porcine fibroblasts from X4mm skin punch biopsies (n=8) was evaluated. RESULTS:
      Mechanically strained cultures of fibroblasts showed a homogeneous multilayer
      matrix infiltration and a regular cell alignment in the direction of strain axis
      after 7 days, as well as a de novo production of extracellular matrix proteins
      compared to the static control. A large amount of viable fibroblasts was easily
      obtained from small skin punch biopsies. CONCLUSION: This study shows that
      continuous multiaxial stimuli improve proliferation and extracellular matrix
      synthesis of mature fibroblasts reseeded on a biological matrix making this a
      feasible autologous tissue engineered graft for penile surgery. For the clinical
      setting fibroblasts harvested from small skin biopsies can be a comfortable cell
      source.

PMID- 15149753
TI  - Endoscopic treatment of vesicoureteral reflux with polydimethylsiloxane in adult
      women.
AB  - OBJECTIVES: Subureteral injection of bulking agents to a refluxing ureteral
      orifice is an attractive alternative to open repair. We record our experience of
      the endoscopic subureteral injection of polydimethylsiloxane in women for
      vesicoureteral reflux (VUR). METHODS: From January 1997 to December 2001, 30
      women (mean age 34.9 years) with 43 refluxing ureters underwent endoscopic
      treatment. The grade of VUR was I, II, III, and IV in 10, 16, 13, and 4 ureters,
      respectively. The indication for the procedure was VUR with a history of
      pyelonephritis in women of childbearing age or in whom antibiotic prophylaxis had
      been unsuccessful. All women underwent voiding cystourethrogram at 3 months and
      then yearly after the procedures. Follow-up ranged from 12 to 60 months (mean
      26.5 months). RESULTS: Reflux was corrected in 34 ureters after a single
      injection; only 3 ureters needed a 2nd injection. The overall success rate was
      86.0%: for grades I, II, III, and IV was 90.0%, 87.5%, 76.9%, and 100%
      respectively. The mean hospital stay was 1.31 days (range 1-8 days), and no
      remarkable surgical complications occurred. Most of the patients in whom VUR was
      cured or improved showed a reduction in laboratory-proven urinary infection
      rates. CONCLUSIONS: The endoscopic subureteral injection of polydimethylsiloxane
      in women with vesicoureteral reflux is an effective therapy with no associated
      morbidity.

PMID- 15149754
TI  - Changes of renal blood flow in nephroptosis: assessment by color Doppler imaging,
      isotope renography and correlation with clinical outcome after laparoscopic
      nephropexy.
AB  - OBJECTIVE: Previously, we have detected changes in renal blood flow secondary to
      nephroptosis by assessing the renal resistive index (RI) using color Doppler
      imaging (CDI). The aim of the current study was to compare two diagnostic
      methods, CDI and isotope renography (IRG), for detection of renal blood flow
      impairment in patients with nephroptosis. METHODS: 26 patients with nephroptosis
      and flank pain underwent CDI and isotope renography (IRG) before and after
      laparoscopic nephropexy. The RI was assessed in segmental arteries with the
      patient in both the supine and erect position. Pre- and postoperative patient
      symptoms, results of Doppler measurements and IRG findings were assessed.
      RESULTS: Preoperatively, 23 of 26 symptomatic patients showed a mean reduction in
      RI of more than 0.10 on the affected side, while only 7 of 26 patients had
      abnormal findings on preoperative IRGs. Postoperatively, none of the patients
      with preoperative changes in Doppler parameters showed any posture-related
      changes in RI. On postoperative IRG, obtained in 4 of 7 patients, normalization
      of renal perfusion was documented. Twenty out of 26 patients were asymptomatic
      postoperatively; in the remaining 6 patients symptoms were markedly improved.
      CONCLUSION: Impairment of renal blood flow due to nephroptosis was detected with
      both CDI and IRG. RI measurement by CDI appears to be significantly more
      sensitive in detecting renal blood flow impairment. RI should be assessed in
      patients with nephroptosis and may impact on the decision for laparoscopic
      nephropexy.

PMID- 15149755
TI  - The "B-bladder"-an ileocolonic neobladder with a chimney: surgical technique and
      long-term results.
AB  - OBJECTIVES: A modified version of the "Le Bag" ileocolonic neobladder with a
      "Studer"-like ileal chimney (B-bladder) is presented. The surgical technique,
      perioperative complications, and long-term results, including cancer control and
      continence, are described. METHODS: Twenty-nine patients underwent radical
      cystectomy and urinary diversion to an orthotopic ileocolonic neobladder with an
      ileal chimney. All operations were done by a single surgeon. Preoperative,
      perioperative and postoperative data were recorded. Median duration of follow-up
      was 3.4 years. RESULTS: The operation was technically successful in all cases.
      Late complications included recurrent urinary tract infection (17%) and uretero
      neobladder anastomotic stricture (3%), both at acceptable rates. Postoperative
      daytime continence was excellent. Cancer control was satisfactory during follow
      up; 11 patients (38%) died of disease progression with distant metastases. Median
      survival was 71.1 months. CONCLUSIONS: The B-bladder maintains the simplicity of
      preparation of the original "Le-Bag" neobladder while gaining the advantages of
      ureteral anastomosis to an ileal chimney. The incidence of perioperative
      complications is low and long-term results with regard to cancer control,
      continence, and complications are excellent.

PMID- 15149756
TI  - Growth, differentiation and senescence of normal human urothelium in an organ
      like culture.
AB  - OBJECTIVE: To examine the kinetics of growth, differentiation and senescence of
      normal human urothelium in an organoid-like culture model. MATERIALS AND METHODS:
      Micro-dissected normal human urothelium explants were grown on porous membranes
      pretreated with various matrix components. Between 5 and 30 days of culture, cell
      proliferation was assessed by BrdU incorporation. Differentiation was evaluated
      on the basis of cytokeratin (Ck) and uroplakin (UP) expression. Epidermal growth
      factor family mRNA expression was monitored during explant outgrowth. Senescence
      was assessed by measuring endogenous beta-galactosidase activity and p16(INK4a)
      mRNA expression. RESULTS: Collagen IV was the most efficient matrix component for
      urothelial cell expansion. BrdU incorporation by urothelial cells was 5% between
      15 and 30 days, corresponding to steady-state urothelium in vivo. Heparin-binding
      EGF (HB-EGF), Amphiregulin (AR) and Transforming Growth Factor alpha (TGF alpha)
      expression correlated with increased cell proliferation. UPII expression was
      stable throughout culture. P16(INK4a) mRNA expression and beta-galactosidase
      activity increased on day 25, giving signs of senescence. CONCLUSIONS: This model
      retains many characteristics of the urothelium in vivo. It can be used for
      pharmacological studies between 15 to 25 days and to study mechanisms such as
      wound healing, proliferation and senescence.

PMID- 15149757
TI  - Time course and histology of urethrocutaneous fistula formation in a porcine
      model of urethral healing.
AB  - OBJECTIVE: Urethrocutaneous fistula is a well-known complication of hypospadias
      surgery and is reported in 5-10% of repairs. Using a previously described
      juvenile pig model, we present a histological analysis of the healing of the
      ventral aspect of the urethral repair and describe the histological mechanism of
      fistula formation. MATERIALS AND METHODS: Twelve juvenile pigs underwent ventral,
      longitudinal urethral incision and closure over a 5-French feeding tube. The
      ventral aspect was closed in running fashion using two closure techniques and
      three suture types in each animal. Three animals were sacrificed on postoperative
      day 3, three on day 5, three on day 12, one on day 14, and two on day 21. Closure
      was one-layered incorporating urethral mucosa in the animals sacrificed on days
      3, 5, and 21. An extra-mucosal suture technique was used in the group sacrificed
      on day 12. Sections of the penis were cut, paraffin embedded, and treated with
      Hematoxylin and Eosin staining. RESULTS: Fistulae were seen in 12 specimens and
      in association with each suture type. Fewer sections of the extra-mucosal
      technique showed fistulization. Fistulae lined with immature epithelium were seen
      by day 5. Mature fistulae were observed by day 12. Skin epithelium and urethral
      mucosa migrated along suture tracts. By days 12 and 21, in addition to mature
      fistulae, several sections showed well-healed ventral repairs with clearly
      extramucosal suture tracts. CONCLUSIONS: Fistula formation begins early in the
      healing process after ventral urethral repair. Incorporation of urethral mucosa
      in the ventral repair is a substrate for fistula formation with rapid migration
      of urethral mucosa and skin epithelium into suture tracts. The importance of a
      multi-layered repair and extra-mucosal suture technique are thus emphasized with
      respect to urethral repair. Whether the mucosal or dermal migration along suture
      tracts can be attenuated or prevented by changing the biochemical environment
      awaits further investigation.

PMID- 15149758
TI  - Estimation of radiation doses from (137)Cs to frogs in a wetland ecosystem.
AB  - Currently, there is no established methodology to estimate radiation doses to non
      human biota. Therefore, in this study, various dose models were used to estimate
      radiation doses to moor frogs (Rana arvalis) in a wetland ecosystem contaminated
      with (137)Cs. External dose estimations were based on activity concentrations of
      (137)Cs in soil and water, considering changes in habitat over a life-cycle.
      Internal doses were calculated from the activity concentrations of (137)Cs
      measured in moor frogs. Depending on the dose model used, the results varied
      substantially. External dose rates ranged from 21 to 160 mGy/y, and internal dose
      rates varied between 1 and 14 mGy/y. Maximum total dose rates to frogs were below
      the expected safe level for terrestrial populations, but close to the suggested
      critical dose rate for amphibians. The results show that realistic assumptions in
      dose models are particularly important at high levels of contamination.

PMID- 15149759
TI  - Natural radioactivity and radiation exposure in the high background area at
      Chhatrapur beach placer deposit of Orissa, India.
AB  - A high natural background radiation area is reported for the Chhatrapur beach
      placer deposit of Orissa state, on the southeastern coast of India, due to the
      presence of radiogenic heavy minerals. The average activity concentrations of
      radioactive elements 232Th, 238U and 40K were measured by gamma-ray spectrometry
      using a HPGe detector, and found to be 2500 +/-1850, 230 +/- 140 and 120 +/- 35
      Bq kg-1, respectively, for the bulk sand samples. The absorbed gamma dose rates
      in air due to the naturally occurring radionuclides varied from 375 to 5000 nGy h
      1, with an average value of 1625 +/- 1200 nGy h-1. The external annual effective
      dose rate of the region ranged from 0.46 to 6.12 mSv y-1, with an average value
      of 1625 +/- 1200 mSv y-1. The absorbed gamma dose rate levels of Chhatrapur beach
      area were similar to the monazite sand-bearing high background radiation areas of
      southern and southwestern coastal tracts of India and other similar areas of the
      world. The major contributors to the enhanced level of radiation are monazite and
      zircon sands.

PMID- 15149760
TI  - Radon time variations and deterministic chaos.
AB  - Radon concentrations were continuously measured outdoors, in the living room and
      in the basement at 10 min intervals for a month. Radon time series were analyzed
      by comparing algorithms to extract phase space dynamical information. The
      application of fractal methods enabled exploration of the chaotic nature of radon
      in atmosphere. The computed fractal dimensions, such as the Hurst exponent (H)
      from the rescaled range analysis, Lyapunov exponent (lambda) and attractor
      dimension, provided estimates of the degree of chaotic behavior. The obtained low
      values of the Hurst exponent (0 < H < 0.5) indicated anti-persistent behavior
      (non-random changes) of the time series, but the positive values of lambda
      pointed out the grate sensitivity on initial conditions and the deterministic
      chaos that appeared due to radon time variations. The calculated fractal
      dimensions of attractors indicated more influencing (meteorological) parameters
      on radon in the atmosphere.

PMID- 15149761
TI  - Occupational exposure of phosphate mine workers: airborne radioactivity
      measurements and dose assessment.
AB  - Under the Egyptian program for radiation safety and control, airborne
      radioactivity measurements and radiological dose assessment were conducted in
      some phosphate and uranium mines. Abu-Tartor mine is one of the biggest
      underground phosphate mines in Egypt. Airborne radioactivity, radon ((222)Rn) and
      its short-lived decay products (progenies) and thoron ((220)Rn), were measured in
      selected locations along the mine. The environmental gamma and workers dose
      equivalent rate (mSv/y) were measured inside and outside the mine using thermo
      luminescence dosimeters (TLD). The results were presented and discussed. The
      calculated annual effective dose due to airborne radioactivity is the main source
      of occupational exposure and exceeding the maximum recommended level by ICRP-60
      inside the mine tunnels. A number of recommendations are suggested to control the
      occupational exposures.

PMID- 15149762
TI  - Simulation of the dispersion of nuclear contamination using an adaptive Eulerian
      grid model.
AB  - Application of an Eulerian model using layered adaptive unstructured grids
      coupled to a meso-scale meteorological model is presented for modelling the
      dispersion of nuclear contamination following the accidental release from a
      single but strong source to the atmosphere. The model automatically places a
      finer resolution grid, adaptively in time, in regions were high spatial numerical
      error is expected. The high-resolution grid region follows the movement of the
      contaminated air over time. Using this method, grid resolutions of the order of 6
      km can be achieved in a computationally effective way. The concept is illustrated
      by the simulation of hypothetical nuclear accidents at the Paks NPP, in Central
      Hungary. The paper demonstrates that the adaptive model can achieve accuracy
      comparable to that of a high-resolution Eulerian model using significantly less
      grid points and computer simulation time.

PMID- 15149763
TI  - Review and assessment of models for predicting the migration of radionuclides
      from catchments.
AB  - The present paper summarises the results of the review and assessment of models
      developed for predicting the migration of radionuclides from catchments to water
      bodies. The models were classified and evaluated according to their main
      methodological approaches. A retrospective analysis of the principles
      underpinning the model development in relation to experimental finding and
      results was carried out. It was demonstrated that most of the various conceptual
      approaches of different modellers can be integrated in a general, harmonised
      perspective supported by a variety of experimental evidences. Shortcomings and
      advantages of the models were discussed.

PMID- 15149764
TI  - Radon concentrations in groundwater in Busan measured with a liquid scintillation
      counter method.
AB  - In this paper, we present the first measurement of radon concentrations in
      drinking groundwater from private and public deep-bored wells located in the
      south-eastern area of Korea. The measurements were carried out on 439 samples by
      using a liquid scintillation method. The results show that the radon
      concentrations of the samples range from 0 to about 300 Bq l(-1). We find that
      Sasang ward shows the highest median value of radon concentration among 13
      different wards, while Jung ward has the lowest. We find that the radon
      concentrations are highly dependent on the type of geological rock aquifers.

PMID- 15149765
TI  - Viscerotropic and neurotropic disease following vaccination with the 17D yellow
      fever vaccine, ARILVAX.
AB  - Yellow fever vaccine associated viscerotropic (YFV-AVD) and neurotropic (YFV-AND)
      diseases have been recently identified in various countries. Previously post
      vaccination multiple organ system failure was recognised as a rare serious
      adverse event of yellow fever vaccination and 21 cases of post-vaccinal (YFV)
      encephalitis had been recorded. Incidence data is not available. On investigation
      of vaccine surveillance reports from Europe following distribution of more than 3
      million doses of ARILVAX trade mark, four cases each of YFV-AVD and YFV-AND were
      found (each 1.3 cases per million doses distributed) for the period 1991 to 2003.
      The incidence for each is higher after 1996 (2.5 cases per million doses
      distributed). The incidence of these adverse events appears to be very low with
      ARILVAX trade mark. Similar incidence data is required from other countries for
      comparison.

PMID- 15149767
TI  - Susceptibility of various mouse strains to systemically- or aerosol-initiated
      tularemia by virulent type A Francisella tularensis before and after immunization
      with the attenuated live vaccine strain of the pathogen.
AB  - The following study determined whether commonly available mouse strains could be
      used to reveal vaccines capable of protecting against aerosol exposure to
      virulent type A strains of Francisella tularensis. The attenuated live vaccine
      strain (LVS) of the pathogen, F. tularensis LVS, was used as the model vaccine
      for these studies. The results showed that most mouse strains survived
      intradermal immunization with 10(5)cfu of LVS, except for A/J mice the majority
      of which died following exposure to 10(4)cfu (colony forming units). Most LVS
      immunized mouse strains survived subsequent i.d. challenge with >50 LD(50) of a
      virulent type A strain of the pathogen. However, all mouse strains tested
      remained susceptible to lethal infection by a low dose ( approximately 20 cfu)
      aerosol challenge with virulent F. tularensis even after vaccination with LVS,
      though immunized C3H/HeN mice appeared to be slightly more resistant than the
      rest to such an assault.

PMID- 15149766
TI  - Sub-compartmentalization of the gastrointestinal (GI) immune system determined
      with microbeads that differ in release properties.
AB  - Immunization of two specific regions of the murine GI tract of two types of mice
      with ovalbumin (OVA) encapsulated in microbeads with two different pH-sensitive
      coatings allowed a more precise analysis of this compartment of the mucosal
      immune system. Acute, chronic and pervasive immunization protocols were utilized
      in an attempt to stimulate specific types of immunity. Chronic immunization
      potentiated antibody isotypes influenced by type 2 T helper cells (T(h)2).
      Pervasive immunization of both regions of the GI tract mimicked chronic
      immunization, stimulating high levels of OVA-reactive IgE. Acute immunization was
      best able to potentiate isotypes influenced by type 1 T helper cells (T(h)1) and
      a sequential segregated immunization protocol allowed the targeting of T(h)1-like
      memory responses.

PMID- 15149768
TI  - Sequence variation in pertussis S1 subunit toxin and pertussis genes in
      Bordetella pertussis strains used for the whole-cell pertussis vaccine produced
      in Poland since 1960: efficiency of the DTwP vaccine-induced immunity against
      currently circulating B. pertussis isolates.
AB  - The present study indicates that the appearance of the B. pertussis harbouring
      prn2 gene allele variant (not found among clinical isolates before 1990s) may
      have been induced by long-term vaccination in Poland with DTP-composed vaccine
      strains presenting exclusively prn1. However, ptxS1A allele of pertussis toxin
      subunit S1 encoding gene, predominant in the currently isolated B. pertussis
      strains, has been found in vaccine strains used for whole-cell pertussis
      component (wP) production of DTP vaccine in 1960-1978. This outrules the
      possibility that the appearance of ptxSIA allele might be related to vaccine
      pressure driven by non-ptxS1A vaccine strains used for long-term immunization
      with wP. Intranasal challenge animal model testing the efficiency of the
      clearance of B. pertussis strains harbouring different ptxS1/prn allele gene
      combinations revealed that currently produced DTwP vaccine may not contain
      adequate B. pertussis vaccine strains, since isolates with gene variants
      different from those observed in vaccine strains were eliminated from the lungs
      of the immunized animals with lower efficiency.

PMID- 15149769
TI  - An approach to a FMD vaccine based on genetic engineered attenuated pseudorabies
      virus: one experiment using VP1 gene alone generates an antibody responds on FMD
      and pseudorabies in swine.
AB  - Foot-and-mouth disease (FMD) and pseudorabies (PR) are two important infectious
      diseases in swine. An attenuated pseudorabies virus (PRV) has been successfully
      used as a gene delivery vector for the development of live-viral vaccines. In
      this study, a recombinant PRV-VP1 virus was constructed by fusioning the VP1 gene
      of FMD virus in frame to the N-terminal sequence of the gG gene of PRV. To test
      the protective immunity, 15 FMDV sero-negative white swine were divided into
      three groups and immunized with the recombinant PRV-VP1 virus, commercial FMD
      vaccine and vector virus (TK(-)/gG(-)/LacZ(+)), respectively, and challenged
      intramuscularly with 20 minimal infecting doses (MID) of virulent type O FMDV 4
      weeks after booster immunization. Swine vaccinated with PRV-VP1 acquired
      antibodies against both FMDV and PRV, however, anti-FMDV antibodies were much
      lower than those vaccinated with the commercial FMD vaccine. Our results
      suggested that the recombinant PRV-VP1 virus, which only expressed FMDV VP1 gene
      controlled by PRV gG promoter, could not protect swine from the challenge of 20
      MID type O FMDV, but could delay and reduce the clinical symptoms of FMD.

PMID- 15149770
TI  - Experimental immunisation and protection of guinea pigs with Vibrio cholerae
      toxoid and mucinases, neuraminidase and proteinase.
AB  - As measured by fluid accumulation in ileal loops, Vibrio cholerae mucinase
      complex, with or without toxoid, protected guinea pigs from challenges with V.
      cholerae live organisms and enterotoxin. The neuraminidase and proteinases of the
      complex were combined in modified oil emulsion or aluminum hydroxide adjuvants
      and the resultant vaccines given by the parenteral or oral routes. There was
      little difference between the two types of adjuvant. Control of stomach acidity
      improved oral vaccination. Animals injected intramuscularly (i.m.) with toxoid
      containing vaccines were protected from challenge with cholera toxin (CT) whereas
      those given oral doses were not. Toxoid plus killed V. cholerae cells elicited a
      more effective protection against toxin challenge than killed V. cholerae cells
      alone. Vaccines containing mucinases, with or without toxoid, protected the
      animals from a live V. cholerae challenge. The anti-mucinase immune response may
      prevent adhesion of the V. cholerae cells and hence reduce delivery of toxin to
      receptors. These mucinases, neuraminidase and proteinases, may be useful
      components of acellular, toxoided cholera vaccines for human immunisation.

PMID- 15149771
TI  - DNA immunization with plasmids expressing hCGbeta-chimeras.
AB  - Human chorionic gonadotropin has been used as an anti-fertility vaccine and as a
      target for cancer immunotherapy. We have explored the use of DNA immunization
      with the aim of improving the immunogenicity of this hormone. Stimulating the
      muscle with electric pulses following intramuscular injection of plasmids
      expressing hCGbeta resulted in higher levels of human chorionic gonadotropin
      (hCG)-specific antibodies, which could be further enhanced following a protein
      boost with hCG mixed with adjuvant. DNA vaccines encoding a membrane attached or
      a secreted form of hCGbeta produced similar-albeit relatively modest-antibody
      responses. Providing hCGbeta with additional T cell help by vaccinating with a
      plasmid encoding a hCGbeta-hFc fusion protein did not further increase the
      antibody levels in the immunized animals. However, immunization of mice with a
      construct encoding hCGbeta fused to C3d(3) produced significantly lower antibody
      levels relative to mice immunized with the hCGbeta-alone expression plasmid, even
      though the hCGbeta-C3d(3) chimera was expected to facilitate cross-linking of the
      antigen-specific B-cell receptor and CR2 thereby lowering the threshold of
      activation. Thus the limiting factor determining the antibody levels following
      hCGbeta immunization, at least for DNA immunization, is related to the amount of
      protein available rather than the form of protein produced or lack of T cell
      epitopes.

PMID- 15149772
TI  - Liposome adjuvants prepared from the total polar lipids of Haloferax volcanii,
      Planococcus spp. and Bacillus firmus differ in ability to elicit and sustain
      immune responses.
AB  - Immune stimulating activity was compared for lipid vesicles consisting of the
      total polar lipids of an archaeon Haloferax volcanii, and the eubacteria
      Planococcus spp. and Bacillus firmus. Each total polar lipid extract readily
      formed liposomes of similar size, within which the protein antigen ovalbumin was
      entrapped, with comparable loading and internalization. Subcutaneous immunization
      of mice resulted in anti-ovalbumin antibody titers for all adjuvants, with memory
      recall responses that were significantly greater with the archaeal lipid (H.
      volcanii versus Planococcus). More striking, induction of cytotoxic T cell
      activity against the entrapped antigen, measured 10 days following a single
      vaccination (primary response) rapidly declined by week 7 (secondary response
      after injections on days 0 and 21) in mice immunized with Planococcus spp.
      liposomes, but was sustained in mice immunized with H. volcanii archaeosomes.
      Surprisingly, antigen free-Planococcus liposomes evoked potent non-specific
      inflammatory cytokine production (IL-12 and IL-6) by dendritic cells whereas
      archaeal H. volcanii vesicles evoked little inflammatory cytokines. This
      suggested that overt inflammatory response might not necessarily aid sustenance
      of immunity. B. firmus liposomes consisted of phosphatidylglycerol,
      phosphatidylethanolamine and cardiolipin and was an ineffective CTL adjuvant,
      even for initiating a primary response. Considering that the polar lipids of H.
      volcanii and Planococcus spp. both consist of the same lipid classes
      (sulfoglycolipids, phosphoglycerols, and cardiolipins), the unique ability of
      archaeosomes to maintain antigen-specific T cell immunity may be attributable to
      a property of the archaeal 2,3-diphytanylglycerol lipid core.

PMID- 15149773
TI  - Does a population survey provide reliable influenza vaccine uptake rates among
      high-risk groups? A case-study of The Netherlands.
AB  - All European countries have recommendations for influenza vaccination among the
      elderly and chronically ill. However, only a few countries are able to provide
      data on influenza uptake among these groups. The aim of our study is to
      investigate whether a population survey is an effective method of obtaining
      vaccination uptake rates in the different risk groups and to find out what
      reasons people give as to why they have accepted or refused influenza vaccination
      and whether this varies among the risk groups. A mail questionnaire was sent out
      to households in The Netherlands, the response rate was 73%. This resulted in
      data for 4037 individuals on influenza and influenza vaccination during the 2001
      2002 influenza season. The uptake rates and size of different risk groups from
      the panel survey were comparable with other national representative sources (from
      the National Information Network of GPs (LINH) and Statistics Netherlands (CBS)).
      The main reason cited for undergoing vaccination was the existence of a chronic
      condition. The main reasons for refraining from vaccination were having enough
      resistance to flu and ignorance about the recommendations. In The Netherlands,
      the GP is the main administrator of influenza vaccines. We believe that
      population surveys may be useful for revealing influenza vaccination uptake rates
      for the groups at risk. When combined with questions about reasons for undergoing
      vaccination, the results may provide useful policy information and can be used to
      direct vaccination campaigns at under-vaccinated risk groups or to target the
      information campaign more effectively.

PMID- 15149774
TI  - Immunogenicity and bactericidal activity in mice of an outer membrane protein
      vesicle vaccine against Neisseria meningitidis serogroup A disease.
AB  - Serogroup A Neisseria meningitidis organisms of the subgroup III have caused
      epidemics of meningitis in sub-Saharan Africa since their introduction into the
      continent in 1987. The population structure of these bacteria is basically
      clonal, and these meningococci are strikingly similar in their major outer
      membrane antigens PorA and PorB. Protein-based vaccines might be an alternative
      to prevent epidemics caused by these meningococci; thus, we developed an outer
      membrane vesicle (OMV) vaccine from a serogroup A meningococcal strain of
      subgroup III. The serogroup A OMV vaccine was highly immunogenic in mice and
      elicited significant bactericidal activity towards several other serogroup A
      meningococci of subgroup III. The IgG antibodies generated were in immunoblot
      shown to be mainly directed towards the PorA outer membrane protein. The results
      presented demonstrate the potential of an OMV vaccine as an optional strategy to
      protect against meningococcal disease caused by serogroup A in Africa.

PMID- 15149775
TI  - Using computer simulations to compare pertussis vaccination strategies in
      Australia.
AB  - High levels of notified pertussis in adolescents and adults, persisting severe
      disease (hospitalization and deaths) in infants despite high childhood
      immunization coverage, together with the availability of adult-formulated
      pertussis vaccines, have made alternate strategies for vaccine control of
      pertussis an important issue in Australia. An age-structured computer simulation
      model was used to compare the likely effects of adopting different vaccination
      strategies in Australia on pertussis transmission by age group over a 50 year
      time period. Epidemiological parameters and vaccination coverage in Australia
      were estimated from previous pertussis modeling studies and existing data. In the
      simulations, replacing the pertussis booster at 18 months with a booster dose for
      adolescents at an age between 12 and 17 years, assuming 80% coverage, led to
      decreases in pertussis cases of 30% in children of ages 0-23 months (who have the
      highest complication rates) and of 25% in adolescents, but an increase of 15% in
      cases in 2-4-year-old children. The simulations did not suggest any shift of
      pertussis cases into the adult child-bearing years. Varying parameter values in
      the simulations in a series of sensitivity analyses showed the model predictions
      to be robust over a plausible range. The results of these simulations suggest
      that the recent change in the Australian pertussis vaccination schedule,
      replacing the 18 month dose with a pertussis booster in 15-17-year-old
      adolescents, is very likely to reduce overall pertussis incidence in Australia
      without increasing the cost of the current vaccine program.

PMID- 15149776
TI  - The number needed to vaccinate (NNV) and population extensions of the NNV:
      comparison of influenza and pneumococcal vaccine programmes for people aged 65
      years and over.
AB  - The number needed to treat (NNT) and population extensions of the NNT describe
      the population outcomes of disease treatment, usually for chronic diseases. We
      have developed similar measures for vaccine preventable diseases based on the
      number needed to vaccinate. These measures quantify the number of people, or the
      number of vaccine doses, needed to prevent one event due to disease per year and
      allow the calculation of the vaccine cost to prevent one event due to disease per
      year. We used this method to compare influenza and pneumococcal vaccine
      programmes for people aged 65 years or more. We calculated the vaccine cost
      (dollars AUD) to prevent a case of disease, a hospitalisation or a death due to
      influenza or invasive pneumococcal disease each year in this age group. For
      influenza, the vaccine costs were dollars 598 to prevent one case per year,
      dollars 10787 per hospitalisation prevented and dollars 74801 per death prevented
      each year. We assumed all cases of invasive pneumococcal disease were
      hospitalised so the vaccine cost of dollars 11494 per case prevented was the same
      as the vaccine cost per hospitalisation prevented, while the vaccine cost per
      death prevented each year was dollars 49972. These results suggest the vaccine
      costs for the prevention of one hospitalisation or one death each year due to
      invasive pneumococcal disease among the elderly in Australia would be similar to
      the costs for the prevention of one hospitalisation or death due to influenza.

PMID- 15149777
TI  - Impaired response rates, but satisfying protection rates to influenza vaccination
      in dialysis patients.
AB  - Dialysis patients show impaired responses to several vaccines. Limited recent
      data are available on influenza vaccination in these patients. In the 1998-1999
      influenza season, 44 dialysis patients received a standard trivalent vaccination
      followed by a booster two months later. The serum antibody responses in these
      patients were compared with those found in healthy subjects. A fourfold rise in
      serum hemagglutination inhibition titre was achieved in 23-58% of all patients.
      Protective titres were reached in 53-93% of the patients. Since protective
      antibody titers can be induced, it is recommended to vaccinate dialysis patients
      annually against influenza.

PMID- 15149778
TI  - Metabolism of MDCK cells during cell growth and influenza virus production in
      large-scale microcarrier culture.
AB  - The production of equine influenza in Madin-Darby canine kidney (MDCK) cells in
      large-scale microcarrier culture is described with detailed on- and off-line
      analytical data during cell growth and virus replication. Metabolite
      concentration profiles for glucose, glutamine, lactate and ammonium are shown.
      Lactate and ammonium concentrations were always below inhibiting levels.
      Concentration profiles for essential and non-essential amino acids of the cell
      culture medium are discussed. During cell growth proline was released into the
      medium with a significant rate while two amino acids, serine and methionine were
      almost depleted. After infection, virus titer increased after a delay of 10-16 h
      whereas first changes in amino acid metabolism could be observed within 4h post
      infection. Here, glutamate and aspartate increase correlated to virus release
      kinetics, indicating cell disruption and apoptosis. Starting with a moi of 0.025
      resulted in a maximum virus yield of 2.4 log HA/100 microl at 44 h post
      infection.

PMID- 15149780
TI  - Burden of hospitalizations attributable to rotavirus infection in children in
      Spain, period 1999-2000.
AB  - The aim of this study is to provide estimates on the incidence of rotavirus
      infection requiring hospitalization in children <or=5 years of age during the
      1999-2000 period in Spain and the associated direct cost of these
      hospitalizations. Hospital admissions attributable to rotavirus were estimated by
      using data on confirmed laboratory reports of rotavirus and hospital admissions
      due to acute gastroenteritis. During the study period a total of 32541 cases of
      pathogens responsible for acute gastroenteritis were reported to the
      microbiological information national system (SIM) and 14.0% were rotavirus. The
      proportion of laboratory-confirmed rotavirus cases was extrapolated to the total
      number of hospitalizations for acute gastroenteritis in children <or=5 years of
      age. An annual incidence of 1.0 hospital admissions attributable to rotavirus per
      1000 persons <or=5 years of age was found, although during the winter season it
      reached 2.5 hospitalizations per 1000. Overall, the estimated annual number of
      days of hospitalization attributable to rotavirus was 8742 days that results in a
      cost of 3.6 million per year.

PMID- 15149779
TI  - Pneumococcal vaccines: an update on current strategies.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality in infants,
      children and the elderly. Despite the availability of excellent antimicrobial
      therapy and adequate health care systems, respiratory diseases and invasive
      infections caused by pneumococci still comprise a major health problem. The
      emerging resistance to penicillin and other commonly used antibiotics underscores
      the importance of the development of novel vaccine strategies to combat
      pneumococcal disease. Although the 23-valent polysaccharide (PS) vaccine is
      immunogenic and protective in most adults and children over 5 years of age, they
      fail to protect children under 2 years of age. Fortunately, the recent conjugate
      vaccines have shown to be highly efficacious in preventing invasive diseases in
      this risk group. Moreover, promising results regarding prevention of pneumonia
      and acute otitis media have been published. Unfortunately, protection is raised
      against a limited number of pneumococcal serotypes, and serotype replacement and
      subsequent vaccine failure have become a serious concern. Currently, several
      pneumococcal surface proteins are considered as alternative vaccine candidates
      because of their serotype-independence. Thus far, pneumococcal surface adhesin A
      (PsaA) has proven to be highly protective against colonization in animal models.
      Moreover, pneumococcal surface protein A (PspA) and pneumolysin have shown to
      elicit protection against invasive diseases. Future research will elucidate their
      true potential in protecting humans. In this paper we discuss the present
      knowledge on pneumococcal vaccines and the current status of novel vaccine
      strategies.

PMID- 15149781
TI  - Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus,
      diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and
      Haemophilus influenzae type b conjugate vaccine, for primary immunization of
      infants.
AB  - Safety, reactogenicity and immunogenicity of GSK Biologicals' hexavalent DTPa-HBV
      IPV/Hib vaccine (Infanrix)hexa) was assessed when used for primary vaccination at
      3, 4 and 5 months of age (N = 2163), compared to the separate administration of
      DTPa-IPV/Hib and HBV vaccines (N = 720). A similar safety and reactogenicity
      profile was demonstrated for both vaccine regimens, as well as a good immune
      response for all antigen components. By offering protection against six diseases
      in a series of single injections, the hexavalent DTPa-HBV-IPV/Hib vaccine was
      shown to be a safe, well tolerated and immunogenic alternative to primary
      immunization with licensed separately administered vaccines.

PMID- 15149782
TI  - Effective immunotherapy against canine visceral leishmaniasis with the FML
      vaccine.
AB  - The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy
      of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally
      infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected
      dogs when seropositive to FML but completely asymptomatic. The clinical signs of
      the experimentally infected, symptomatic dogs only disappeared after the complete
      vaccination. Protection was obtained in 3/5 animals that remained asymptomatic,
      IDR positive and parasite free, 1 year after infection. Furthermore, the
      asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels,
      increasing IgG2 levels and 79-95% of positive DTH response, during the whole
      experiment. Twenty-two months after complete vaccination, no obits due to
      visceral leishmaniasis were recorded and 90% of these dogs were still
      asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala
      azar obits were recorded in a control group that received no treatment during the
      same period, and that was FML-seropositive and asymtpomatic at the beginning of
      the assay. Our results indicate that the FML-vaccine was effective in the
      immunotherapy against visceral leishmaniasis of asymptomatic infected dogs.
      Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS
      analysis, in dogs submitted to immunotherapy, suggesting their non-infectious
      condition. All animals showed as well significantly increased percents of CD8
      lymphocytes as expected for Quillaja saponin (QuilA) vaccine treatments.

PMID- 15149783
TI  - A protective immune response in mice to viral components other than hemagglutinin
      in a live influenza A virus vaccine model.
AB  - Previously, we generated influenza A viruses that possess chimeric type (A/B)
      hemagglutinins (HA), in which immunogenic regions of type A HA were replaced with
      those of type B HA, and showed that these viruses were attenuated in mice (J.
      Virol. 77 (2003) 8031). Here, we intranasally immunized mice with these viruses
      and then challenged them with a wild-type A virus to assess a protective immune
      response to viral components other than HA in the form of a live virus. All
      immunized mice survived challenge with a lethal dose of wild-type virus; none or
      a limited amount of virus, if any, was recovered from nasal turbinates or lungs
      of the mice 3 days post-challenge. These results provide direct evidence that
      immune responses to viral components other than HA confer protection against
      influenza A virus infection in a mouse model, suggesting the usefulness of live
      vaccines for viruses that have undergone antigenic drift with respect to HA, or
      for viruses with heterosubtypic HAs.

PMID- 15149784
TI  - Pulmonary delivery of respiratory syncytial virus DNA vaccines using
      macroaggregated albumin particles.
AB  - At present there is no safe and effective vaccine for respiratory syncytial virus
      (RSV). DNA vaccines encoding RSV surface glycoproteins are one option being
      examined. Current methods to deliver DNA vaccines generally require repeated high
      dose intramuscular or intradermal administration for effectiveness. In this
      study, we examine the efficacy of pulmonary DNA vaccination using low dose DNA
      vaccines encoding the RSV F glycoprotein conjugated to macroaggregated albumin
      (MAA-F). Single vaccination of BALB/c mice with 1 microg MAA-F was ineffective,
      however mice boosted with an additional 1 microg MAA-F, or vaccinated a single
      time with 10 microg MAA-F, developed substantially improved immunity associated
      with reduced viral titers, increased anti-F antibody responses, and enhanced Th1
      and Th2 intracellular cytokine responses. This study shows that MAA may be a
      useful carrier for RSV DNA vaccines.

PMID- 15149786
TI  - Impact of vector-priming on the immunogenicity of a live recombinant Salmonella
      enterica serovar typhi Ty21a vaccine expressing urease A and B from Helicobacter
      pylori in human volunteers.
AB  - Orally administered recombinant Salmonella vaccines represent an attractive
      option for mass vaccination programmes against various infectious diseases.
      Therefore, it is crucial to gather knowledge about the possible impact of
      preexisiting immunity to carrier antigens on the immunogenicity of recombinant
      vaccines. Thirteen volunteers were preimmunized with Salmonella typhi Ty21a in
      order to evaluate the effects of prior immunization with the carrier strain.
      Then, they received three doses of 1-2 x 10(10) viable organisms of either the
      vaccine strain S. typhi Ty21a (pDB1) expressing subunits A and B of recombinant
      Helicobacter pylori urease (n = 9), or placebo strain S. typhi Ty21a (n = 4).
      Four volunteers were preimmunized and boosted with the vaccine strain S. typhi
      Ty21a (pDB1). No serious adverse effects were observed in any of the volunteers.
      Whereas none of the volunteers primed and boosted with the vaccine strain
      responded to the recombinant antigen, five of the nine volunteers preimmunized
      with the carrier strain showed cellular immune responses to H. pylori urease
      (56%). This supports the results of a previous study in non-preimmunized
      volunteers where 56% (five of nine) of the volunteers showed a cellular immune
      response to urease after immunisation with S. typhi Ty21a (pDB1).

PMID- 15149785
TI  - Human immunodeficiency virus type 2 DNA vaccine provides partial protection from
      acute baboon infection.
AB  - We determined if the genetic adjuvants, granulocyte-macrophage colony stimulating
      factor (GM-CSF) and B7-2, could improve the immunogenicity and efficacy of an HIV
      2 DNA vaccine. The vaccine consisted of the HIV-2 tat, nef, gag, and env genes
      synthesized using optimized codons and formulated with cationic liposomes.
      Baboons (Papio cynocephalus hamadryas) were immunized by the intramuscular,
      intradermal, and intranasal routes with these expression constructs and
      challenged with HIV-2(UC2) by the intravaginal route. In the first month after
      HIV-2 vaginal challenge, the baboons receiving the HIV-2 DNA vaccine with or
      without the genetic adjuvants had significant reductions in the viral loads in
      the peripheral blood mononuclear cells (PBMC) (P = 0.028) while the reductions in
      their plasma viremia were suggestive of a protective effect (P = 0.1). These data
      demonstrate that partial protection against HIV-2 vaginal challenge, as measured
      by reduced viral load, can be achieved using only a DNA vaccine formulation.

PMID- 15149787
TI  - Immunisation schedules for non-replicating nasal vaccines can be made simple by
      allowing time for development of immunological memory.
AB  - Mice immunised intranasally with multiple doses of outer membrane vesicles (OMVs)
      from group B meningococci developed antibody responses that depended on the
      interval between doses. High levels of antibodies in saliva and extracts of
      faeces were induced within 4 weeks after an OMV vaccine had been given at weekly
      intervals, whereas the antibody responses in these samples were negligible when
      given four times at 1-day or 1-h intervals, or as one large dose. Only modest
      responses were obtained in serum after 4 weeks, however, whether the vaccine had
      been given repeatedly at any schedule, including the 1-week interval, or as one
      dose. On the other hand, two large doses given 8 weeks apart induced booster
      antibody responses in both serum and secretions that matched the responses from a
      second series of the four smaller doses. Intranasal immunisations may thus
      stimulate immunological memory more rapidly in secretions than in serum. In order
      to secure adequate systemic responses by a minimum of doses, nasal vaccines
      should therefore be given at intervals longer than 4 weeks, in harmony with the
      intervals recommended for injectable vaccines.

PMID- 15149789
TI  - Moderate exercise improves antibody response to influenza immunization in older
      adults.
AB  - Influenza vaccine efficacy is reduced among adults over age 65 and a significant
      number of vaccinated elderly may remain susceptible to influenza virus infection.
      The effect of moderate exercise training on the immune response to influenza
      immunization was evaluated in this study. Twenty-seven adults >or=age 64 were
      assigned to an exercise group (n= 14) or a control group (n = 13). The subjects
      exercised at 65-75% heart rate reserve (HRR), 25-30 min, 3 days per week, for 10
      months. Controls did not change activity. Subjects were immunized with trivalent
      influenza vaccine before and after the exercise intervention. After the exercise
      intervention, exercisers exhibited a greater mean fold increase (MFI) in antibody
      titer to influenza A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) than
      controls, and a greater Granzyme B activity to A/Panama/2007/99 than controls.
      These findings suggest that exercise may enhance the mean fold increase in
      antibody titer in response to influenza immunization if the influenza antigen was
      contained in the previous year's vaccine.

PMID- 15149788
TI  - Evaluation of a recombinant salivary gland protein (thrombostasin) as a vaccine
      candidate to disrupt blood-feeding by horn flies.
AB  - The potential for controlling blood-feeding by the cattle pest, Haematobia
      irritans irritans (horn fly), was tested by vaccination against thrombostasin
      (TS), an inhibitor of mammalian thrombin that is released into skin during horn
      fly blood-feeding. The increase in blood meal size that occurred for flies
      feeding on sensitized non-vaccinated hosts was blocked and egg development in
      female flies was delayed when horn flies fed on rabbits and cattle immunized with
      recombinant TS. This demonstration of the impact of disrupting TS action by
      vaccination provides a novel approach toward control of this veterinary pest and
      offers a paradigm for limiting blood-feeding in other medically-important insect
      species.

PMID- 15149790
TI  - Assessing the impact of wastage on pediatric vaccine immunization formulary costs
      using a vaccine selection algorithm.
AB  - Pediatric immunization is an important factor in providing protection against
      numerous common preventable diseases. The success of the pharmaceutical industry
      in developing new pediatric vaccines has resulted in a crowded recommended
      immunization schedule requiring several clinic visits over the first 12 years of
      life. Operations research models have been developed and used to make
      economically sound procurement choices from among a growing number of competing
      vaccine products. One factor that has not been incorporated into such models is
      the economic impact of wastage on such decisions. This paper reports results
      obtained from a vaccine selection algorithm that incorporates vaccine wastage
      data. The lowest overall cost formularies comparing no wastage costs with wastage
      costs are presented. A sensitivity analysis of the vaccine formulary with respect
      to the wastage rates associated with each available vaccine is provided. The
      maximum permissible wastage rate for each vaccine is determined for which the
      vaccine earns a place in the lowest overall cost formulary. This research
      provides health maintenance organizations and healthcare providers information
      that can be used to gain a better understanding of wastage and its impact on
      pediatric formulary costs.

PMID- 15149791
TI  - The apoptotic and necrotic effects of tomatine adjuvant.
AB  - Tomatine adjuvant, consisting of tomatine, n-octyl-beta-d-glucopyranoside (OGP),
      phosphatidylethanolamine and cholesterol is unique in that when combined with
      soluble protein antigen it elicits a cytotoxic T lymphocyte (CTL) response in
      immunized animals. The mechanisms underlying this property are unknown. In an
      attempt to understand how tomatine activates cellular immunity, we examined its
      potential to induce apoptosis. Thus in the present study, cell death of EL4
      thymoma cells induced by whole adjuvant and the surface-active components in the
      formulation was examined. Cytotoxicity was monitored using the MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and lactate dehydrogenase
      release assays, apoptosis and necrosis were quantified by flow cytometry using
      Annexin V and propidium iodide staining, and morphology was examined by Hoechst
      33342 staining. Flow cytometric analysis demonstrated the appearance of the sub
      G1 phase in cells treated with these agents and Annexin V/PI staining showed that
      all three agents induced both apoptosis and necrosis in EL4 cells in a
      concentration-dependent manner. Tomatine was effective at much lower
      concentrations than OGP, suggesting that the majority of the effect of whole
      adjuvant could be attributed to this component. Microscopic examination of EL4
      cells after treatment with these agents revealed morphological features of
      apoptosis, including chromatin condensation and DNA fragmentation. Pretreatment
      with zVAD-fmk did not block cell death induced by these agents, showing that
      tomatine adjuvant-induced EL4 cell apoptosis is caspase-independent.

PMID- 15149792
TI  - Effects of Mycoplasma hyopneumoniae vaccine on pigs naturally infected with M.
      hyopneumoniae and porcine reproductive and respiratory syndrome virus.
AB  - The effects of a single-dose Mycoplasma hyopneumoniae vaccine was studied in
      growing pigs. Each of 24 vaccinated cohorts of approximately 1200 pigs reared in
      separate barns was matched by time, farm site, and sex with unvaccinated cohorts.
      Pigs were naturally exposed to M. hyopneumoniae and porcine reproductive
      respiratory syndrome virus (PRRSv). Daily weight gain was 42 g per pig per day
      higher and mortality rate was 15.2/1000 pigs lower for vaccinated cohorts. Age at
      PRRSv onset was associated with mortality rate, but did not modify vaccine
      effects. M. hyopneumoniae vaccination was effective in promoting growth in spite
      of concurrent PRRSv infection.

PMID- 15149793
TI  - Pressure-inactivated FMDV: a potential vaccine.
AB  - Foot-and-mouth disease virus (FMDV) is the causative agent of the foot-and-mouth
      disease (FMD). Alternative FMD vaccines have been pursued due to important
      disadvantages of the one currently in use. High hydrostatic pressure (HP) has
      been observed to inactivate some viruses. Here, we investigated the effects of HP
      on FMDV O1 Campos-Vallee (CVa) infectivity. A treatment consisting of 2.5 kbar at
      -15 degrees C and 1M urea, completely abolished FMDV infectivity, maintaining the
      integrity of its capsid structure. Moreover, its ability to elicit neutralizing
      antibody production in rabbits was preserved. Taken together, our results suggest
      that HP could be a safe, simple, cheap and reproducible way for viral vaccine
      production.

PMID- 15149794
TI  - Family physician perspectives on barriers to childhood immunisation.
AB  - New Zealand (NZ) has inadequate vaccine coverage and associated disease
      outbreaks. International research illustrates the importance of provider
      behaviour in improving vaccine uptake. To understand the immunisation knowledge,
      views, concerns and educational needs of NZ family physicians, qualitative and
      quantitative national data was gathered from randomised telephone surveys.
      Response rate was 60% with respondents' characteristics closely matched to key
      demographics of NZ family physicians. The most significant barrier to improving
      immunisation rates identified was parental concern over vaccine safety and
      associated misconceptions. The second major barrier identified was lack of
      funding to health providers. A clear need for improvement in family physician
      knowledge of contraindications to vaccines was highlighted. Family physicians
      expressed a need for better resources to more effectively address parental fears
      and misconceptions. Strategies to address these issues include an increased focus
      on family physician educational needs, extra resources to assist with more
      effective communication to parents and a review of the present funding of
      providers for immunisation services.

PMID- 15149795
TI  - Effectiveness of the linkage of child care and maternity payments to childhood
      immunisation.
AB  - In 1998, Australia enacted comprehensive national legislation making receipt of
      the maternity immunisation allowance (MIA) and the child care benefit (CCB)
      conditional on evidence of age-appropriate immunisation. We assessed the impact
      of this policy on immunisation status using a nationally representative
      population-based case-control study of 589 fully immunised controls and 190
      incompletely immunised cases, aged 28-31 months. Immunisation status was
      significantly associated with parent awareness of the MIA (adjusted odds ratio
      (aOR) = 3.34, 95% CI = 2.28 - 4.91) and CCB (aOR = 2.08, 95% CI = 1.30 - 3.34).
      Only 31% of the 219 control parents who were receiving the CCB reported that they
      could continue to afford child care without the assistance of the CCB. The use of
      legislated financial immunisation incentives for parents appears to be widely
      accepted among Australian parents and to have had an impact on immunisation
      uptake. The policy may serve as a model for other comparable countries.

PMID- 15149796
TI  - Avian adenovirus CELO recombinants expressing VP2 of infectious bursal disease
      virus induce protection against bursal disease in chickens.
AB  - To develop a CELO virus vector that can induce protection against infectious
      bursal disease, CELO viruses expressing the host-protective antigen VP2 of
      infectious bursal disease virus (IBDV) were constructed. In the engineered
      recombinants, the VP2 gene (the 441-first codons of the IBDA polyprotein) was
      placed under the control of the CMV promoter. Two positions in the CELO genome
      were chosen to insert the VP2 expression cassette. The recombinants were found
      apathogenic, when inoculated by different routes and even at high doses (up to
      10(8) per animal). Chickens vaccinated oro-nasally with these different
      recombinants and challenged with very virulent IBDV were found to be poorly
      protected. In contrast, when inoculated with one or two (subcutaneous or
      intradermic) injections of CELOa-VP2, the chickens showed no clinical signs and
      no mortality after challenge. In the vaccinated chickens, the titers of
      neutralization antibody reached 7-9 values, showing that protection could be
      explained by the induction of a sufficient humoral response. After challenge, the
      weight ratio Bursa of Fabricius/body was about 2.5 per thousand, a value similar
      to that obtained with the commercial Bur706 vaccine. However, histological
      lesions in the Bursa of Fabricius were observed, showing that a complete
      protection was not totally achieved. Contact transmission was evidenced.
      Protection was also obtained when inoculation of CELOa-VP2 was carried out in
      ovo. Prime-boost strategies were also tested with the CELOa-VP2 vector used in
      association with the purified VP2 antigen, or DNA encoding VP2 or a CELO vector
      expressing chicken myeloid growth factor (cMGF). None of these regimens were
      shown to substantially increase the level of protection when compared to double
      CELOa-VP2 inoculations. These results indicate that CELO-based vectors are useful
      to safely induce a strong protective immunity against vvIBDV in chickens.

PMID- 15149797
TI  - Catalysis of phosphoryl transfer from adenosine-5'-triphosphate (ATP) by
      trinuclear "chelate" complexes.
AB  - The chelate ligand 2,9-di(6'-alpha-phenol-n-2',5'-diazahexyl)-1,10-phenanthroline
      (L) was synthesized and fully characterized. This ligand formed six protonated
      species in the solution. The bindings of the ligand to the nucleotide anions ATP,
      ADP and AMP were described in detail, with equilibrium constants given for each
      species formed. The strength of binding increased with the number of protons,
      corresponding to an increase in the number of hydrogen bonds and an increase in
      the coulombic attractive forces. At the same time, the coordination properties of
      the ternary complexes formed from the chelate ligand above, M (M=Zn(2+), Cd(2+))
      and adenosine-5'-triphosphate (ATP) were studied. The metal complexes of the
      chelate recognize the nucleotides via multiple interactions similar to those
      occurring in the center of enzymes. The hydrolysis of ATP was studied with the
      mononuclear and trinuclear chelate complexes.

PMID- 15149798
TI  - Mannose-Escherichia coli interaction in the presence of metal cations studied in
      vitro by colorimetric polydiacetylene/glycolipid liposomes.
AB  - Supramolecular assemblies of liposomes (vesicles) made of diacetylenic lipids and
      synthetic mannoside derivative glycolipid receptors were successfully used to
      mimic the molecular recognition occurring between mannose and Escherichia coli.
      This specific molecular recognition was translated into visible blue-to-red color
      transition (biochromism) of the polymerized liposomes, readily quantified by UV
      visible spectroscopy. Some transition metal cations (Cd(2+), Ag(+), Cu(2+),
      Fe(3+), Zn(2+) and Ni(2+)) and alkali earth metal cations (Ca(2+), Mg(2+) and
      Ba(2+)) were introduced into the system to analyze their effects on specific
      biochromism. Results showed that the presence of Cd(2+), Ag(+), Ca(2+), Mg(2+)
      and Ba(2+) enhanced biochromism. A possible enhancement mechanism was proposed in
      the process of bacterial adhesion to host cells. However, Cu(2+), Fe(3+), Zn(2+)
      and Ni(2+) exhibited inhibitory effects that cooperated with diacetylene lipid
      with a carboxylic group and increased the rigidity of the liposomal outer
      leaflet, blocking changes in the side chain conformation and electrical structure
      of polydiacetylene polymer during biochromism.

PMID- 15149799
TI  - Nickel(II) binding to Cap43 protein fragments.
AB  - Cap43 protein has been tested for metal binding domains. The protein,
      specifically induced by nickel compounds in cultured human cells, had a new mono
      histidinic motif consisting of 10 amino acids repeated three times in the C
      terminus. The 20-Ac-TRSRSHTSEG-TRSRSHTSEG (Thr(341)-Arg-Ser-Arg-Ser-His(346)-Thr
      Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser-His(356)-Thr-Ser-Glu-Gly(360) - peptide 1) and
      the 30-Ac-TRSRSHTSEG-TRSRSHTSEG-TRSRSHTSEG (Thr(341)-Arg-Ser-Arg-Ser-His(346)-Thr
      Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser-His(356)-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser
      His(366)-Thr-Ser-Glu-Gly(370) - peptide 2) amino acids sequence has been analyzed
      as a site for Ni(II) binding. A combined pH-metric and spectroscopic (UV-visible,
      CD, NMR) studies of Ni(II) binding to both fragments were performed. The 20-amino
      acid peptide can bind one and two metal ions while the 30-amino acid fragment
      one, two and three metal ions. At physiological pH, depending on the metal to
      ligand molar ratio, peptide 1 forms the Ni(2)L species while peptide 2 the NiL,
      Ni(2)L and Ni(3)L complexes where each metal ion is coordinated to the imidazole
      nitrogen atom of the histidine residue of the 10-amino acid fragment. Octahedral
      complexes at pH 8-9 and planar 4N complexes with (N(Im), 3N(-)) bonding mode at
      pH above 9, are formed. This work supports the existence of an interesting
      binding site at the COOH-terminal domain of the Cap43 protein.

PMID- 15149800
TI  - Products of Cu(II)-catalyzed oxidation in the presence of hydrogen peroxide of
      the 1-10, 1-16 fragments of human and mouse beta-amyloid peptide.
AB  - The interactions of proteins with reactive oxygen species (ROS) may result in
      covalent modifications of amino acid residues in proteins, formation of protein
      protein cross-linkages, and oxidation of the protein backbone resulting in
      protein fragmentation. In an attempt to elucidate the products of the metal
      catalyzed oxidation of the human (H) and mouse (M) (1-10H), (1-10M), (1-16H) and
      (1-16M) fragments of beta-amyloid peptide, the high performance liquid
      chromatography (HPLC) and matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-TOF MS) methods and Cu(II)/H(2)O(2) as a model oxidizing
      system were employed. Peptide solution (0.50 mM) was incubated at 37 degrees C
      for 24 h with metal:peptide:H(2)O(2) molar ratio 1:1:1 for the (1-16H), (1-16M)
      fragments, and 1:1:2 for the (1-10H), (1-10M) peptides in phosphate buffer, pH
      7.4. Oxidation targets for all peptide studied are the histidine residues
      coordinated to the metal ions. For the (1-16H) peptide are likely His(13) and/or
      His(14), and for the (1-16M) fragment His(6) and/or His(14), which are converted
      to 2-oxo-His. Metal-binding residue, the aspartic acid (D(1)) undergoes the
      oxidative decarboxylation and deamination to pyruvate. The cleavages of the
      peptide bonds by either the diamide or alpha-amidation pathways were also
      observed.

PMID- 15149801
TI  - Relationships between glutamine, glutamate, and GABA in nerve endings under Pb
      toxicity conditions.
AB  - Glutamine (Gln), glutamate (Glu) and gamma-amino butyric acid (GABA) are
      essential amino acids for brain metabolism and function. Astrocytic-derived
      glutamine is the precursor of the two most important neurotransmitters:
      glutamate, an excitatory neurotransmitter, and GABA, an inhibitory
      neurotransmitter. In addition to their roles in neurotransmission these
      neurotransmitters act as alternative metabolic substrates that enable metabolic
      coupling between astrocytes and neurons. The relationships between Gln, Glu and
      GABA were studied under lead (Pb) toxicity conditions using synaptosomal
      fractions obtained from adult rat brains to investigate the cause of Pb
      neurotoxicity-induced seizures. We have found that diminished transport of
      [(14)C]GABA occurs after Pb treatment. Both uptake and depolarization-evoked
      release decrease by 40% and 30%, respectively, relative to controls. Lower
      expression of glutamate decarboxylase (GAD), the GABA synthesizing enzyme, is
      also observed. In contrast to impaired synaptosomal GABA function, the GABA
      transporter GAT-1 protein is overexpressed (possibly as a compensative
      mechanism). Furthermore, similar decreases in synaptosomal uptake of radioactive
      glutamine and glutamate are observed. However, the K(+)-evoked release of Glu
      increases by 20% over control values and the quantity of neuronal EAAC1
      transporter for glutamate reaches remarkably higher levels after Pb treatment. In
      addition, Pb induces decreased activity of phosphate-activated glutaminase (PAG),
      which plays a role in glutamate metabolism. Most noteworthy is that the
      overexpression and reversed action of the EAAC1 transporter may be the cause of
      the elevated extracellular glutamate levels. In addition to the impairment of
      synaptosomal processes of glutamatergic and GABAergic transport, the results
      indicate perturbed relationships between Gln, Glu and GABA that may be the cause
      of altered neuronal-astrocytic interactions under conditions of Pb neurotoxicity.

PMID- 15149802
TI  - Solid state and solution studies of a vanadium(III)-L-cysteine compound and
      demonstration of its antimetastatic, antioxidant and inhibition of neutral
      endopeptidase activities.
AB  - Reaction of one equivalent of vanadium(III) chloride with three equivalents of l
      cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated
      as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was
      performed by microanalysis, circular dichroism (CD) and infrared studies as well
      as room temperature magnetic susceptibility. These studies have shown
      coordination of each HCys- ligand to the VIII atom through an amine nitrogen and
      a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and
      methanol by UV-visible, CD and electron paramagnetic resonance (EPR)
      spectroscopies. According to these studies, it was evident that despite the
      progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were
      also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l
      cysteine were examined for their total antioxidant capacity (TAC) and lag time.
      Compound 1 exhibited significantly greater total antioxidant capacity and lag
      time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant
      capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity
      caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a
      concentration of 10(-3) M, showed inhibition of NEP activity as potent as
      thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited
      less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover,
      the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were
      examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that
      1 prevents significantly lung metastases (only 9.5% of animals treated with 1
      showed metastases), whereas 47-52% of the rats of the control group and those
      treated with l-cysteine and VIVOSO4.5H2O exhibited metastases.

PMID- 15149803
TI  - Bioconjugates of cyclodextrins of manganese salen-type ligand with superoxide
      dismutase activity.
AB  - 6A,6B-Dideoxy-6A,6B-di[(N-salicylidene)amino]-beta-cyclodextrin was synthesized
      and characterized by NMR, UV and CD spectroscopy in order to prepare a N,N(')-bis
      (salicylidene)ethane-1,2-diamine (SalenH(2)) type ligand. The manganese(III)
      complex was synthesized and characterized by UV and cyclic voltammetry and
      compared to EUK-8. The superoxide dismutase (SOD)-like and catalase-like
      activities were tested by indirect assay. The cyclodextrin complex shows a larger
      solubility than EUK-8 and good SOD-like activity. Catalase activity is also
      shown.

PMID- 15149804
TI  - Binding of Cu2+ to S-adenosyl-L-homocysteine hydrolase.
AB  - S-Adenosylhomocysteine (AdoHcy) hydrolase regulates biomethylation and
      homocysteine metabolism. It has been proposed to be a copper binding protein
      playing an important role in copper transport and distribution. In the present
      work, the kinetics of binding and releasing of copper ions was studied using
      fluorescence method. The dissociation constant for copper ions with AdoHcy
      hydrolase was determined by fluorescence quenching titration and activity
      titration methods using ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic
      acid (NTA), and glycine as competitive chelators. The experimental results showed
      that copper ions bind to AdoHcy hydrolase with a K(d) of approximately 10(-11) M.
      The association rate constant was determined to be 7 x 10(6) M(-1)s(-1). The
      releasing of copper ions from the enzyme was found to be biphasic with a k(1) of
      2.8 x 10(-3) s(-1) and k(2) of 1.7x10(-5) s(-1). It is suggested that copper ions
      do not bind to the substrate binding sites because the addition of adenine
      substrate did not compete with the binding of copper to AdoHcy hydrolase.
      Interestingly, it was observed that EDTA could bind to AdoHcy hydrolase with a
      dissociation constant of K(1) = 8.0 x 10(-5) M and result in an increased
      affinity (K(d) = approximately 10(-17) M) of binding of copper ions to the
      enzyme.

PMID- 15149806
TI  - Fluorescence resonance energy transfer from tryptophan to a chromium(III) complex
      accompanied by non-specific cleavage of albumin: a step forward towards the
      development of a novel photoprotease.
AB  - A chromium(III) complex, transdiaqua [N, N'
      propylenebis(salicylideneimino)chromium(III)]perchlorate
      ([Cr(salprn)(H2O)(2)]ClO(4)) in the presence of sodium azide and upon
      photoexcitation was found to bring about non-selective cleavage of bovine serum
      albumin (BSA). Electron paramagnetic resonance (EPR) evidence has been obtained
      for the formation of a Cr(V) species upon photolysis of a solution containing the
      chromium(III) complex and sodium azide. This Cr(V) species non-selectively
      cleaves BSA. The fluorescence excitation spectrum of BSA-[Cr(salprn)(H2O)(2)]+
      adduct showed a band at lambda(max)(ex) nm due to charge transfer transition of
      the chromium(III) complex as well as a prominent band at 290 nm attributable to
      tryptophan absorption. This indicated an efficient Forster type fluorescence
      energy transfer (FRET) from the tryptophan residues to the chromium(III) complex
      indicating that the Cr(III) complex binds in the vicinity of the tryptophan
      residue.

PMID- 15149805
TI  - Electrochemical measurements confirm the preferential bonding of the
      antimetastatic complex [ImH][RuCl(4)(DMSO)(Im)] (NAMI-A) with proteins and the
      weak interaction with nucleobases.
AB  - An electrochemical and biological study of interaction between the prototypical
      antimetastatic drug imidazolium trans
      tetrachlorodimethylsulfoxideimidazoleruthenate (III) complex,
      [ImH][RuCl(4)(DMSO)(Im)] (DMSO = dimethylsulfoxide, Im = imidazole), nicknamed
      NAMI-A, and several biomolecules, namely DNA, bovine (BSA) and human (HSA) serum
      albumin, is reported. Electrochemistry offers great advantages over the existing
      devices based on optical techniques, since it provides rapid, simple, and low
      cost information whether the interaction occurs or not. Moreover, we describe
      some biochemical assays to test the interaction of NAMI-A with ribonucleoprotein
      telomerase and protein Taq polymerase. All the data confirm the preferential
      interaction of NAMI-A with proteins with respect to nucleotides, especially when
      compared with the behaviour of the well-known alkylating drug cisplatin in the
      presence of the same targets.

PMID- 15149808
TI  - Iron(III) complexing ability of carbohydrate derivatives.
AB  - A solution study on the coordinative ability of galactaric acid (GalAH(2)), d
      glucosamine (GlcN) and d-glucosaminic acid (GlcNAH) toward Fe(3+) ion is
      reported. UV spectroscopic study provides useful information to identify complex
      species formation and their stability constants are determined by means of
      potentiometric measurements. GalAH(2) behaves as chelating ligand through
      carboxylic oxygen and alpha-hydroxylic oxygen in the protonated or dissociated
      form depending on pH value. Two complex species [Fe(2)GalA(OH)(4)] and
      Na[FeGalAH(-2)] .2H(2)O are also isolated in the solid state and characterised
      through IR spectroscopy. GlcNAH also binds the Fe(3+) ion through carboxylic and
      hydroxylic groups, while NH(2) group is probably involved in metal coordination
      up to pH 4. GlcN demonstrates low ligating ability at acidic pH and does not
      prevent metal hydroxyde precipitation.

PMID- 15149809
TI  - Complexes of dichloro[2-(dimethylaminomethyl)phenyl-C1,N]gold(III), [Au(damp
      C1,N)Cl2], with formylferrocene thiosemicarbazones: synthesis, structure and
      cytotoxicity.
AB  - Dichloro[2-(dimethylaminomethyl)phenyl- phenyl-C1,N]gold(III), [Au(damp
      C1,N)Cl2], reacts with the formylferrocene thiosemicarbazones derived from 4
      methyl-, 4-phenyl-, 4-ethyl- and 4,4-dimethyl-3-thiosemicarbazides, HFcTSC, to
      give complexes of general formula [Au(Hdamp-1C)Cl(FcTSC)]Cl. These complexes were
      isolated and characterized by elemental analysis, mass spectrometry and IR, 1H
      NMR and (13)C NMR spectroscopy. In some cases, cyclic voltammetric studies were
      carried out and these showed that the complexation of gold affects the redox
      behaviour of the ferrocene unit. The in vitro antitumor activity against the HeLa
      cell line was also determined for the more soluble complexes. The IC(50) values
      were found to be higher than that of cisplatin but the maximum antiproliferative
      activity was similar.

PMID- 15149810
TI  - Luminescent pH sensing and DNA binding properties of a novel ruthenium(II)
      complex.
AB  - A new Ru(II) complex, [Ru(bpy)(2)(dhipH3)](ClO4)(2) (in which bpy=2,2'
      bipyridine, dhipH(3)=3,4-dihydroxy-imidado[4,5-f][1,10]-phenanthroline), was
      synthesized and characterized, and the pH effect on the emission spectra of the
      complex was studied. The interaction of the complex with calf thymus DNA was
      investigated by UV-visible and emission spectroscopy, and viscosity measurements.
      The results suggest that the complex acted as a sensitive luminescent pH sensor
      and a strong ct-DNA intercalator with an intrinsic binding constant of (4.0+/
      0.7) x 10(5) M(-1) in buffered 50 mM NaCl.

PMID- 15149811
TI  - Synthesis, antimicrobial activity and chemotherapeutic potential of inorganic
      derivatives of 2-(4'-thiazolyl)benzimidazole[thiabendazole]: X-ray crystal
      structures of [Cu(TBZH)2Cl]Cl.H2O.EtOH and TBZH2NO3 (TBZH=thiabendazole).
AB  - Thiabendazole (TBZH) reacts with iron(III) nitrate causing protonation of the
      ligand to yield the nitrate salt [TBZH(2)NO(3)] (1). Reaction of TBZH with
      copper(II) acetate results in the deprotonation of the ligand yielding
      [Cu(TBZ)2.(H2O)2] (2). Reactions of TBZH with the chloride, nitrate and
      butanedioate salts of copper(II) yields [Cu(TBZH)2Cl]Cl.H2O.EtOH (3),
      [Cu(TBZH)(2)(NO(3))(2)] (4) and [Cu(TBZH)(O(2)C-CH(2)CH(2)-CO(2))] (5),
      respectively. The TBZH acts as a neutral chelating ligand in 3-5. Molecular
      structures of 1 and 3 were determined crystallographically. In 1, the asymmetric
      unit contains one TBZH(2)(+) cation and one NO(3)(-) anion. The structure of 3
      comprises a five coordinate copper centre with the metal bound to two chelating
      TBZH ligands and one chloride. The geometry is best described as trigonal
      bipyramidal. Hydrogen bonding connects the complex cation with the uncoordinated
      chloride anion and the water and ethanol solvate molecules. Compound 1 and the
      copper complexes 2-5, the metal free ligands and a number of simple copper(II)
      salts were each tested for their ability to inhibit the growth of Candida
      albicans. The metal free TBZH and its nitrate salt (1) exhibited very poor
      activity. Complex 2, in which the TBZH is present as an anionic ligand (TBZ(-)),
      exhibits moderate activity towards the pathogen. Chelation of the neutral TBZH to
      copper centres (complexes 3-5) results in potent anti-candida activity. The
      dimethyl sulphoxide (DMSO) soluble complexes 3 and 4, along with metal free TBZH
      were assessed for their cancer chemotherapeutic potential towards two human
      epithelial-derived cancer model cell lines. Complexes 3 and 4 displayed similar
      dose-dependent cytotoxicity in both cell lines with IC(50) values of
      approximately 50 microM, which were found to be significantly lower than that for
      metal free TBZH.

PMID- 15149812
TI  - Studies on the interaction of Escherichia coli agmatinase with manganese ions:
      structural and kinetic studies of the H126N and H151N variants.
AB  - The H126N and H151N variants of Escherichia coli agmatinase (EC 3.5.3.11) were
      produced by site-directed mutagenesis, and their kinetic and structural
      properties were examined. About 51% and 30% of wild-type activity were expressed
      by fully manganese activated species of the H126N and H151N variants,
      respectively. Mutations were not accompanied by changes in the K(m) value for
      arginine (1.2+/-0.3 mM), K(i) value for putrescine inhibition (3.2+/-0.4 mM),
      molecular weight (M(r) 67,000+/-2000), tryptophan fluorescence properties
      (lambda(max) = 342 nm) or CD spectra of the enzyme. However, the interaction with
      the required manganese ions was significantly altered, as indicated by the
      effects of dialysis of the enzymes against metal-free buffer. We conclude that
      replacement of His151 with asparagine results in the loss of a catalytically
      essential Mn(2+) upon dialysis and concomitant reversible inactivation of the
      H151N mutant, and that the affinity of a more weakly bound Mn(2+) is decreased in
      the H126N variant.

PMID- 15149813
TI  - Syntheses, crystal structures and biological relevance of glycolato and S-lactato
      molybdates.
AB  - Glycolato and S-lactato complexes containing the dioxomolybdenum(VI) moiety have
      been synthesized for studies on the role of the alpha-hydroxycarboxylato anion in
      the iron molybdenum cofactor of nitrogenase. The ligands in these complexes, vis
      K2[MoO2(glyc)2].H2O (H2glyc=glycolic acid, C2H4O3) (1) and (Na2[MoO2(S
      lact)2])3.13H2O (H2lact=lactic acid, C3H6O3) (2) chelate through their alpha
      alkoxyl and alpha-carboxyl oxygen atoms. In contrast, octanuclear
      K6[(MoO2)8(glyc)6(Hglyc)2].10H2O (3) formed by the reduction of the glycolato
      complex (1), features three different ligand binding modes: (i) non-bridging and
      bridging bidentate coordination of alpha-alkoxyl and alpha-carboxyl groups, and
      (ii) bidentate bridging using alpha-carboxyl group, leaving the alpha-alkoxyl
      group free. The octanuclear skeleton shows strong metal-metal interactions. The
      coordination modes in (1) and (2) mimic that of homocitrate to the iron
      molybdenum cofactor (FeMo-co) of nitrogenase. The bidentate coordination of alpha
      alkoxyl and alpha-carboxyl groups shows that bond of alpha-carboxyl group to Mo
      is less susceptible to the oxidation state of molybdenum compared with the Mo
      alpha-alkoxyl bond. This is supported by the dinuclear coordination of alpha
      carboxyl group with free alpha-alkoxyl group in glycolato molybdate(V) (3).

PMID- 15149815
TI  - Involvement of reactive oxygen species in the bactericidal activity of activated
      carbon fibre supporting silver; Bactericidal activity of ACF(Ag) mediated by ROS.
AB  - An activated carbon fibre supporting silver (ACF(Ag)) was tested for its
      antibacterial capacity against Escherichia coli (E. coli). Water that has passed
      through ACF(Ag) demonstrated strong bactericidal ability. This activity decreased
      over the time suggesting that generated bactericidal species were short lifespan.
      Since formation of reactive oxygen species (ROS) might be catalysed by silver
      impregnated and/or ACF itself, implication of ROS and silver was evaluated by the
      use of ROS scavengers and a silver ions neutralizing agent. The role of ROS in
      the E. coli mortality was confirmed by the use of a molecular approach which
      revealed a strong expression of oxidative stress genes.

PMID- 15149816
TI  - Cadmium-induced changes in the membrane of human erythrocytes and molecular
      models.
AB  - The structural effects of cadmium on cell membranes were studied through the
      interaction of Cd(2+) ions with human erythrocytes and their isolated unsealed
      membranes (IUM). Studies were carried out by scanning electron microscopy and
      fluorescence spectroscopy, respectively. Cd(2+) induced shape changes in
      erythrocytes, which took the form of echinocytes. According to the bilayer couple
      hypothesis, this result meant that Cd(2+) ions located in the outer monolayer of
      the erythrocyte membrane. Fluorescence spectroscopy measurements in IUM indicated
      a disordering effect at both the polar headgroup and the acyl chain packing
      arrangements of the membrane phospholipid bilayer. Cd(2+) ions also interacted
      with molecular models of the erythrocyte membrane consisting in bilayers of
      dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine
      (DMPE), representing classes of phospholipids located in the outer and inner
      monolayers the erythrocyte membrane, respectively. X-ray diffraction indicated
      that Cd(2+) ions induced structural perturbation of the polar headgroup and of
      the hydrophobic acyl regions of DMPC, while the effects of cadmium on DMPE
      bilayers were much milder. This conclusion is supported by fluorescence
      spectroscopy measurements on DMPC large unilamellar vesicles (LUV). All these
      findings point to the important role of phospholipid bilayers in the interaction
      of cadmium on cell membranes.

PMID- 15149817
TI  - A model for the misfolded bis-His intermediate of cytochrome c: the 1-56 N
      fragment.
AB  - We have characterized the ferric and ferrous forms of the heme-containing (1-56
      residues) N-fragment of horse heart cytochrome c (cyt c) at different pH values
      and low ionic strength by UV-visible absorption and resonance Raman (RR)
      scattering. The results are compared with native cyt c in the same experimental
      conditions as this may provide a deeper insight into the cyt c unfolding-folding
      process. Folding of cyt c leads to a state having the heme iron coordinated to a
      histidine (His18) and a methionine (Met80) as axial ligands. At neutral pH the N
      fragment (which lacks Met80) shows absorption and RR spectra that are consistent
      with the presence of a bis-His low spin heme, like several non-native forms of
      the parental protein. In particular, the optical spectra are identical to those
      of cyt c in the presence of a high concentration of denaturants; this renders the
      N-fragment a suitable model to study the heme pocket microenvironment of the
      misfolded (His-His) intermediate formed during folding of cyt c. Acid pH affects
      the ligation state in both cyt c and the N-fragment. Data obtained as a function
      of pH allow a correlation between the structural properties in the heme pocket of
      the N-fragment and those of non-native forms of cyt c. The results underline that
      the (57-104 residues) segment under native-like conditions imparts structural
      stability to the protein by impeding solvent access into the heme pocket.

PMID- 15149818
TI  - Validation of semiempirical methods for modeling of corrinoid systems.
AB  - Several semiempirical methods (MNDO-d, PM3tm, PM3-d, PM5, PM6, and AM1-d) have
      been tested against experimental data and density functional theory (DFT) results
      in search for the best methods that can be used for quantum-mechanical-molecular
      mechanics (QM/MM) modeling of corrinoid systems of vitamin B(12) co-factor. It
      has been found that the PM6 parametrization in its present form gives results
      closest to hybrid DFT calculations that are most widely used thus far. In
      comparison with pure DFT and experimental data the best agreement is obtained for
      PM3tm parametrization, while PM6 yields slightly worse results. AM1-d yields bad
      geometry of the corrin moiety. The worst performance was observed for MNDO-d,
      which has severe problem with position and orientation of the alpha-ligands.

PMID- 15149819
TI  - Different modes of DNA cleavage activity of dihydroxo-bridged dicopper(II)
      complexes having phenanthroline bases.
AB  - Dihydroxo-bridged dicopper(II) complexes [(Cu(phen))(2)(mu-OH)(2)](ClO(4))(2)
      (1), [(Cu(dpq))(2)(mu-OH)(2)](ClO(4))(2) (2) and [(Cu(dppz)(DMF))(2)(mu
      OH)(2)](PF(6))(2) (3), where phen, dpq and dppz are 1,10-phenanthroline,
      dipyridoquinoxaline and dipyridophenazine, respectively, are prepared and their
      DNA binding and cleavage properties studied. Complex 3 has been structurally
      characterized by X-ray crystallography. The complexes have a (Cu(2)(mu
      OH)(2))(2+) core with an essentially planar arrangement of two CuN(2)O(2) basal
      planes. The complexes are avid binder to calf thymus DNA (K(app) value of 4.8 x
      10(6) and 5.9 x 10(6) M(-1) for 2 and 3, respectively, from ethidium displacement
      assay) and exhibits significant cleavage of supercoiled (SC) pUC19 DNA in dark in
      presence of mercaptopropionic acid. Besides, the dpq and dppz complexes display
      photo-induced DNA cleavage on UV (312 nm) and red light (632.8 nm) irradiations
      in absence of any additives. Mechanistic investigations reveal minor groove
      binding for the phen and dpq complexes, and major groove preference for the dppz
      species. The oxidative DNA cleavage reactions in presence of mercaptopropionic
      acid as a reducing agent involve hydroxyl radicals. The photo-cleavage reactions
      at UV light involve singlet oxygen as the reactive species, while similar
      reactions on red light irradiation (632.8 nm) proceed through the formation of
      hydroxyl radical. The complexes show significant DNA hydrolase activity in
      absence of any additives under dark reaction conditions.

PMID- 15149820
TI  - Analysis of metal-containing granules in the barnacle Tetraclita squamosa.
AB  - Metal-containing granules were isolated from specimens of the barnacle Tetraclita
      squamosa collected from a metal contaminated site in Hong Kong. The chemical
      composition, crystallographic and morphological properties of the deposits were
      analysed by X-ray powder diffraction, electron microscopy, energy dispersive
      analysis by X-rays and infrared spectroscopy. The most abundant metals were iron,
      calcium and zinc and the major anion was phosphate. Oxalates, carbonates and
      sulfur derivates were also found in small amounts. The deposits were amorphous to
      X-ray and electron diffraction and were approximately spherical in shape with
      diameters between 100 and 500 nm.

PMID- 15149821
TI  - Effects of divalent metal ions on the alphaB-crystallin chaperone-like activity:
      spectroscopic evidence for a complex between copper(II) and protein.
AB  - AlphaB-crystallin is a small heat shock protein, showing chaperone-like activity,
      that is expressed in the lens and in several other tissues. The role of some
      metal ions in the alphaB-crystallin biology starts to be well documented. In some
      neuro-degenerative pathologies, like Parkinson and Alzheimer's diseases, alphaB
      crystallin is expressed at high levels. In the same pathologies an accumulation
      of divalent metal cations is observed. In order to investigate the interactions
      between human alphaB-crystallin and divalent metal ions, the effect of copper,
      zinc and calcium on the chaperone-like activity of the protein has been studied.
      Copper and zinc at concentrations 0.1 and 1 mM significantly increase the
      chaperone-like activity, whereas calcium 1 mM completely inhibits activity.
      Electron paramagnetic resonance (EPR) and circular dichroism (CD) spectra
      indicate the possible complex formation between Cu(II) and protein at
      physiological pH. Molecular modeling calculations, carried out for the probable
      Cu(II) binding site, suggest that a complex with three histidine residues is
      possible.

PMID- 15149823
TI  - Characterization studies and cytotoxicity assays of Pt(II) and Pd(II)
      dithiocarbamate complexes by means of FT-IR, NMR spectroscopy and mass
      spectrometry.
AB  - The precursors [M(ESDTM)Cl(2)] (M=Pt(II), Pd(II);
      ESDTM=EtO(2)CCH(2)(CH(3))NCS(2)Me, S-methyl(ethylsarcosinedithiocarbamate)) were
      synthesized as previously reported [J. Inorg. Biochem. 83 (2001) 31] and used to
      obtain [M(ESDT)Cl](n) (ESDT=ethylsarcosinedithiocarbamate anion) species. The
      complexes formed through reaction between [M(ESDT)Cl](n) and the two chiral amino
      alcohols synephryne (Syn) and norphenylephrine (Nor) have been synthesized, with
      the ultimate goal of preparing mixed dithiocarbamate/amino metal complexes of the
      type [M(ESDT)(Am)Cl] (Am=Syn, Nor). These compounds have been isolated, purified
      and characterized by means of FT-IR, mono- and bidimensional NMR spectroscopy and
      mass spectrometry ESI/MS (electronspray mass spectra). The experimental data
      suggest that in all cases coordination of the dithiocarbamate ligand (ESDT) takes
      a place through the two sulfur atoms, the -NCSS moiety acting as a symmetrical
      bidentate chelating group, in a square-planar geometry around the M(II) ion,
      while the other two coordination positions are occupied by the chlorine atom and
      the amino-alcohol ligand, respectively. In particular, synephrine and
      norphenylephrine appear to be bound to the metal atom through the amino nitrogen
      atom by means of a dative bond. Finally, the biological activity of the new
      complexes has been studied by MTT (tetrazolio salt reduction) test and by
      detecting the inhibition of DNA synthesis and of clonal growth in various cancer
      cell lines. All Pd(II) derivatives showed a noticeable activity very close to
      that of cisplatin, used as reference drug. Moreover, they showed significantly
      reduced cross-resistance to cisplatin in a pair of cell lines (2008/C13*) with
      known acquired cisplatin resistance mechanisms.

PMID- 15149824
TI  - Antioxidants prevent aluminum-induced toxicity in cultured hepatocytes.
AB  - Cellular Al accumulation has been shown to alter iron metabolism and induce
      peroxidative injury. Therefore antioxidants could potentially reduce or prevent
      peroxidative injury in Al-loaded cells. To test this hypothesis we assessed the
      effect of the antioxidants N-acetyl cysteine (NAC), catalase, superoxide
      dismutase (SOD), and tetramethylpiperidine 1-oxyl (TEMPO) in abrogating Al
      associated cell toxicity and melonyldialdehyde (MDA) accumulation in mouse
      hepatocytes. Mouse hepatocytes (MH) were grown in media containing the minimum
      toxic concentration of Al (100 microg/L as Al-transferrin). All antioxidants
      protected MH from injury as assessed by cell growth and enzyme leakage into
      media. The antioxidants did not affect Al uptake by MH, protect MH from lipid
      peroxidation or decrease the reactive iron content of MH. Although antioxidants
      protected Al loaded MH from injury the mechanisms of this effect are unknown.

PMID- 15149825
TI  - A comparative study of adduct formation between the anticancer ruthenium(III)
      compound HInd trans-[RuCl4(Ind)2] and serum proteins.
AB  - Formation of adducts between the antitumor ruthenium(III) complex [HInd]trans
      [RuCl(4)(Ind)(2)] (KP1019) and the plasma proteins serum albumin and serum
      transferrin was investigated by UV-vis spectroscopy, for metal-to-protein ratios
      ranging from 1:1 to 5:1. In both cases, formation of tight metal-protein
      conjugates was observed. Similar spectroscopic features were observed for both
      albumin and transferrin derivatives implying a similar binding mode of the
      ruthenium species to these proteins. Surface histidines are the probable
      anchoring sites for the bound ruthenium(III) ions in line with previous
      crystallographic results. In order to assess the stability of the KP1019-protein
      adducts the influence of pH, reducing agents and chelators was analysed by UV-vis
      spectroscopy. Notably, there was no effect of addition of EDTA on the UV-vis
      spectra of the conjugates. The pH-stability was high in the pH range 5-8.
      Experiments with sodium ascorbate showed that there was just some alteration of
      selected bands. The implications of the present results are discussed in relation
      to the pharmacological behavior of this novel class of antitumor compounds.

PMID- 15149826
TI  - DNA interactions of cobalt(III) mixed-polypyridyl complexes containing asymmetric
      ligands.
AB  - Three novel asymmetric ligands, 3-(pyridine-2-yl)-5,6-diphenyl-as-triazine
      (pdtb), 3-(pyridine-2-yl)-as-triazino[5,6-f]acenaphthylene (pdta) and 3-(pyridine
      2-yl)-as-triazino[5,6-f]phenanthroline (pdtp) and their cobalt(III) complexes
      have been synthesized and characterized. Binding of the three complexes with calf
      thymus DNA (CT-DNA) has been investigated by spectroscopic methods, viscosity,
      cyclic voltammetry, and electrophoresis measurements. The experimental results
      indicate that the size and shape of the intercalated ligand have a marked effect
      on the binding affinity of complexes to CT-DNA. Complexes 2 and 3 have also been
      found to promote cleavage of plasmid pBR322 DNA from the supercoiled form I to
      the open circular form II upon irradiation.

PMID- 15149827
TI  - Equilibrium characterization of the As(III)-cysteine and the As(III)-glutathione
      systems in aqueous solution.
AB  - Some arsenic compounds were the first antimicrobial agents specifically
      synthesized for the treatment of infectious diseases such as syphilis and
      trypanosomiasis. More recently, arsenic trioxide has been shown to be efficient
      in the treatment of acute promyelocytic leukemia. The exact mechanism of action
      has not been elucidated yet, but it seems to be related to arsenic binding to
      vicinal thiol groups of regulatory proteins. Glutathione is the major
      intracellular thiol and plays important roles in the cellular defense and
      metabolism. This paper reports on a study of the interactions between
      arsenic(III) and either cysteine or glutathione in aqueous solution. The behavior
      observed for the As(III)-glutathione system is very similar to that of As(III)
      cysteine. In both cases, the formation of two complexes in aqueous solution was
      evidenced by NMR and electronic spectroscopies and by potentiometry. The
      formation constants of the cysteine complexes [As(H(-1)Cys)(3)], log K =
      29.84(6), and [As(H(-2)Cys)(OH)(2)](-), log K = 12.01(9), and of the glutathione
      complexes [As(H(-2)GS)(3)](3-), log K = 32.0(6), and [As(H(-3)GS)(OH)(2)](2-),
      log K = 10(3) were calculated from potentiometric and spectroscopic data. In both
      cases, the [As(HL)(3)] species, in which the amine groups are protonated,
      predominate from acidic to neutral media, and the [As(L)(OH)(2)] species appear
      in basic medium (the charges were omitted for the sake of simplicity).
      Spectroscopic data clearly show that the arsenite-binding site in both complexes
      is the sulfur atom of cysteine. In the [As(L)(OH)(2)] species, the coordination
      sphere is completed by two hydroxyl groups. In both cases, arsenic probably
      adopts a trigonal pyramidal geometry. Above pH 10, the formation of [As(OH)(2)O](
      ) excludes the thiolates from arsenic coordination sites. At physiological pH,
      almost 80% of the ligand is present as [As(HL)(3)].

PMID- 15149828
TI  - Multi-step analysis of Hg2+ ion inhibition of jack bean urease.
AB  - We performed a multi-step analysis of the inhibition of jack bean urease by
      Hg(2+) ions that included residual activity measurements after incubation of the
      enzyme with the metal ion, reactivation of Hg(2+)-inhibited urease, protection of
      urease with thiol reagents prior to incubation with Hg(2+), progress curve
      analysis, and spectroscopic assay of thiol groups in urease-Hg(2+) complexes with
      a cysteine selective agent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Hg(2+)
      ions were found to form stable complexes with urease that could rapidly be
      reversed only by the treatment with dithiotreitol, and not by dilution or
      dialysis. The residual activity data interpreted in terms of the Hill equation
      revealed the multisite Hg(2+) inhibition of urease, and along with the DTNB thiol
      assay they demonstrated the involvement in the reaction with Hg(2+) of six
      cysteine residues per enzyme subunit, including the active-site flap cysteine.
      The molar ratios of the inhibitor and enzyme imply that the inhibition consists
      of the formation of RSHgX complexes, X being a water molecule or an anion. The
      time-dependent Hg(2+) inhibitory action on urease determined in the system
      without enzyme preincubation was best described by slow-binding mechanism with
      the steady-state inhibition constant K(i) = 1.9 nM (+/-10%).

PMID- 15149829
TI  - A possible transport mechanism for aluminum in biological membranes.
AB  - The transport mechanism of aluminum in lysosomes extracted from rat liver has
      been investigated in this paper. The experimental evidence supports the
      hypothesis that aluminum is transported inside lysosomes in the form of an
      Al(OH)(3) electroneutral compound, the driving force being the internal acidic
      pH. This mechanism could help to explain the presence of aluminum in cells in
      many illnesses.

PMID- 15149830
TI  - Tuning properties of radial phantom motion aftereffects.
AB  - Motion aftereffects are normally tested in regions of the visual field that have
      been directly exposed to motion (local or concrete MAEs). We compared concrete
      MAEs with remote or phantom MAEs, in which motion is perceived in regions not
      previously adapted to motion. Our aim was to study the spatial dependencies and
      spatiotemporal tuning of phantom MAEs generated by radially expanding stimuli.
      For concrete and phantom MAEs, peripheral stimuli generated stronger aftereffects
      than central stimuli. Concrete MAEs display temporal frequency tuning, while
      phantom MAEs do not show categorical temporal frequency or velocity tuning. We
      found that subjects may use different response strategies to determine motion
      direction when presented with different stimulus sizes. In some subjects, as
      adapting stimulus size increased, phantom MAE strength increased while the
      concrete MAE strength decreased; in other subjects, the opposite effects were
      observed. We hypothesise that these opposing findings reflect interplay between
      the adaptation of global motion sensors and local motion sensors with inhibitory
      interconnections.

PMID- 15149831
TI  - 3D flash lag illusion.
AB  - Objective of this research is to study the presence of 3D flash lag illusion
      created by a moving object that has a motion-in-depth and a flash object. An
      object consisting of two thin sticks was simulated to approach the subject who
      observed it with a stereoscope. In the process of approaching, another stick was
      briefly presented in the middle of the moving sticks. Five human subjects took
      part in our experiments and all perceived 3D flash lag illusion. The perceived
      depth created by 3D flash lag illusion was measured by two different
      psychophysical experiments, by use of a vernier caliper and by a method of
      nulling with another depth cue. We studied relation between the perceived depth
      and the presentation distance. The experimental results indicate that the
      perceived gap by 3D flash lag illusion is independent from the presentation
      distance.

PMID- 15149832
TI  - Poor encoding of position by contrast-defined motion.
AB  - Second-order (contrast-defined) motion stimuli lead to poor performance on a
      number of tasks, including discriminating form from motion and visual search. To
      investigate this deficiency, we tested the ability of human observers to monitor
      multiple regions for motion, to code the relative positions of shapes defined by
      motion, and to simultaneously encode motion direction and location. Performance
      with shapes from contrast-defined motion was compared with that obtained from
      luminance-defined (first-order) stimuli. When the position of coherent motion was
      uncertain, direction-discrimination thresholds were elevated similarly for both
      luminance-defined and contrast-defined motion, compared to when the stimulus
      location was known. The motion of both luminance- and contrast-defined structure
      can be monitored in multiple visual field locations. Only under conditions that
      greatly advantaged contrast-defined motion, were observers able to discriminate
      the positional offset of shapes defined by either type of motion. When shapes
      from contrast-defined and luminance-defined motion were presented under
      comparable conditions, the positional accuracy of contrast-defined motion was
      found to be poorer than its luminance-defined counterpart. These results may
      explain some, but possibly not all, of the deficits found previously with second
      order motion.

PMID- 15149833
TI  - Multiplicative nonlinearity in the perception of apparent motion.
AB  - Evidence is reported indicating that the perception of apparent motion is better
      predicted by the multiplicative combination of luminance changes at two element
      locations than by the sum or squared-sum of the luminance changes, or by the
      motion energy in the stimulus. Because the results were obtained with a stimulus
      for which motion was specified by simultaneous luminance changes, they support a
      Reichardt-style motion detector model, but without the asymmetrical delay
      specified by current versions. Motion direction in the modified model relies on
      asymmetrical stimulus information rather than asymmetrical delay. That is, one
      subunit of the detector responds to changes in luminance toward the background
      luminance (the start of the motion path), and the other to changes in luminance
      away from the background luminance (the end of the motion path).

PMID- 15149834
TI  - Decision and metrics of refixations in reading isolated words.
AB  - Eye movements were recorded during the reading of long words presented in
      isolation. Overall, the decision to refixate was found to depend on both length
      and frequency of the word, while refixation amplitude depended only on word
      length. This finding corroborates the assumption that most refixation saccades
      are preplanned on the basis of the parafoveal word length. However, cancellation
      of such a plan is possible and could be linked to the lexical processing during
      the first fixation into the word. Finally, a small proportion of refixations are
      corrective saccades, related to an oculomotor error. Theoretical implications for
      models of eye movement control during reading are discussed.

PMID- 15149835
TI  - Distribution of short-wavelength-sensitive cones in human fetal and postnatal
      retina: early development of spatial order and density profiles.
AB  - We analysed spatial density and distribution of short-wavelength-sensitive
      photoreceptors (S-cones) in developing and adult human retinae using antibody
      against short-wavelength-sensitive opsin. Statistical tests indicate that before
      20 weeks of gestation (WG) the S-cone mosaic is not distinguishable from a random
      distribution, but by 20 WG is significantly different from a random distribution
      in the perifoveal region, as reported previously for adult retina. Changes in
      spatial density during development are consistent with displacement of the
      photoreceptor population towards the incipient fovea so that prior to 20 WG, peak
      S-cone density is >1.7 mm from the fovea, but is within 800 microm of the fovea
      by 20 WG.

PMID- 15149836
TI  - Human observers are biased in judging the angular approach of a projectile.
AB  - How do we decide whether an object approaching us will hit us? The optic array
      provides information sufficient for us to determine the approaching trajectory of
      a projectile. However, when using binocular information, observers report that
      trajectories near the mid-sagittal plane are wider than they actually are. Here
      we extend this work to consider stimuli containing additional depth cues. We
      measure observers' estimates of trajectory direction first for computer rendered,
      stereoscopically presented, rich-cue objects, and then for real objects moving in
      the world. We find that, under both rich cue conditions and with real moving
      objects, observers show positive bias, overestimating the angle of approach when
      movement is near the mid-sagittal plane. The findings question whether the visual
      system, using both binocular and monocular cues to depth, can make explicit
      estimates of the 3-D location and movement of objects in depth.

PMID- 15149837
TI  - The allometry and scaling of the size of vertebrate eyes.
AB  - We compiled data from the literature and colleagues to examine the relationship
      between eye axial length and body weight for vertebrates as well as birds,
      mammals, reptiles, and fishes independently. After fitting the data to
      logarithmic and semi-logarithmic models, we found that axial length of vertebrate
      eyes does obey a conventional logarithmic relationship with body weight rather
      than a semi-logarithmic relationship as suggested by the results of previous
      studies. The regression slopes and intercepts appear to be characteristic of
      various animal groups. The axial length of the eye is largest in birds and
      primates, smaller in other mammals (especially rodents) and reptiles, and widely
      varying in fishes.

PMID- 15149838
TI  - Dopaminergic modulation of photopic temporal transfer properties in goldfish
      retina investigated with the ERG.
AB  - The influence of dopamine (DA) through either D1- or D2-dopamine receptors (D1
      /D2-R) onto temporal transfer properties of the retina has been investigated
      using the ERG. Single flash responses and flicker responses were measured in the
      vitreous under photopic illumination conditions after application of either D1
      /D2-R agonists or antagonists. All DA-R drugs did change the single flash
      responses, but only blockade of D2-R or activation of D1-R also changed the
      temporal transfer properties. In the Bode plot the gain characteristic was
      changed and thereby the upper limit frequency reduced. The action of DA is
      discussed on the base of a membrane resonance model in the outer retina versus a
      feed-forward inhibition model in the inner retina.

PMID- 15149839
TI  - A silicon early visual system as a model animal.
AB  - Examples that show the transfer of our basic knowledge of brain function into
      practical electronic models are rare. Here we present a user-friendly silicon
      model of the early visual system that contributes to animal welfare. The silicon
      chip emulates the neurons in the visual system by using analog Very Large Scale
      Integration (aVLSI) circuits. It substitutes for a live animal in experiment
      design and lecture demonstrations. The neurons on this chip display properties
      that are central to biological vision: receptive fields, spike coding,
      adaptation, band-pass filtering, and complementary signaling. Unlike previous
      laboratory devices whose complexity was limited by the use of discrete components
      on printed circuit boards, this battery-powered chip is a self-contained patch of
      the visual system. The realistic responses of the chip's cells and the self
      contained adjustment-free correct operation of the chip suggest the possibility
      of implementation of similar circuits for visual prosthetics.

PMID- 15149840
TI  - Light deprivation slows but does not prevent the loss of photoreceptors in
      taurine transporter knockout mice.
AB  - Taurine transporter knockout mice show severe retinal degeneration at an early
      age. The study was designed to determine whether degeneration also takes place in
      the absence of light. Mice were maintained up to 6 weeks of age in cyclic
      lighting or in total darkness. Degeneration took place in both groups, but was
      more rapid in animals exposed to standard cyclic illumination. At the
      ultrastructural level the retinas showed features characteristic of apoptosis but
      not of necrosis. CONCLUSIONS: Cell differentiation is not seriously affected by
      the lack of a functional taurine transporter but mature photoreceptor cells do
      not survive without an intact transporter, even in the dark.

PMID- 15149841
TI  - Wnt and beta-catenin signaling target the expression of ecto-5'-nucleotidase and
      increase extracellular adenosine generation.
AB  - Solid tumors, which routinely experience necrosis and ischemia, release and
      degrade adenine nucleotides. This process may lead, depending on the expression
      of enzymes that regulate adenosine, to the generation of extracellular adenosine.
      Since genes encoding ecto-5'-nucleotidase (eN) and adenosine deaminase (ADA)
      contain TCF/LEF consensus binding sites, we asked whether Wnt/beta-catenin
      signaling, a pathway that is deregulated in several human tumors, targets the
      expression of these genes and thus influence extracellular adenosine generation.
      Our results show that beta-catenin strongly increased the activity of the 969-bp
      promoter of eN and this increase depended on the presence of TCF-1 transcription
      factor. Reciprocally, the eN promoter activity was decreased by co-transfection
      of APC, a beta-catenin antagonist. The expression of endogenous eN mRNA was
      increased either in Cos-7 cells transfected with a mutated beta-catenin and TCF-1
      or in Rat-1 cells transformed by the Wnt-1 oncogene. In Rat-1 cells, expression
      of Wnt-1 correlated with increased eN protein levels and enzymatic activity and a
      concomitant decrease of adenosine deaminase mRNA and enzymatic activity. This
      expression profile is accompanied by a threefold increase in the generation of
      extracellular adenosine. Our study demonstrates a link between the Wnt signaling
      and the regulation of two enzymes that control the metabolism of adenosine.

PMID- 15149842
TI  - Onset of direct 17-beta estradiol effects on proliferation and c-fos expression
      during oncogenesis of endometrial glandular epithelial cells.
AB  - In normal endometrial glandular epithelial cells (GEC), 17beta-estradiol (E2)
      enhances proliferation and c-fos expression only in the presence of growth
      factors. On the contrary, growth factors are not required for the E2 effects in
      cancerous cells. Thus, a repression of E2 action could exist in normal cells and
      be turned off in cancerous cells, allowing a direct estrogen-dependent
      proliferation. To verify this hypothesis, we established immortalized and
      transformed cell models, then investigated alterations of E2 effects during
      oncogenesis. SV40 large T-antigen was used to generate immortalized GEC model
      (IGEC). After observation of telomerase reactivation, IGEC model was transfected
      by activated c-Ha-ras to obtain transformed cell lines (TGEC1 and TGEC2). The
      phenotypic, morphological, and genetic characteristics of these models were
      determined before studying the E2 effects. In IGEC, the E2 action on
      proliferation and c-fos expression required the presence of growth factors, as
      observed in GECs. In TGECs, this action arose in the absence of growth factors.
      After IGEC transformation, the activation of ras pathway would substitute the
      priming events required for the release of repression in GEC and IGEC and thus
      permit direct E2 effects. Our cell models are particularly suitable to
      investigate alterations of gene regulation by E2 during oncogenesis.

PMID- 15149843
TI  - Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat
      keratinocytes.
AB  - Hyaluronan (hyaluronic acid, HA) is an abundant matrix component between
      keratinocytes of the epidermis in vivo, but its function there remains unclear.
      We used a lift culture model, in which rat epidermal keratinocytes (REKs)
      stratify at an air-liquid interface, to ask whether HA may regulate epidermal
      proliferation and/or differentiation. In this model, early markers of
      differentiation (keratin 10), and later markers (profilaggrin, keratohyalin
      granules, cornified layers) are faithfully expressed, both temporally and
      spatially. HA, measured using two different analytical techniques, accumulated to
      high levels only in the presence of an intact basement membrane that seals the
      epidermal compartment. To test whether HA has a functional role in
      differentiation, Streptomyces hyaluronidase (StrepH, 1 U/ml; digests >95% of HA
      within 4 h) was added daily to lift cultures during stratification time-course
      experiments over 5 days. In StrepH-treated cultures, the expression of
      profilaggrin and the number and size of keratohyalin granules were significantly
      increased relative to controls using semiquantitative histological analyses. The
      StrepH-related accumulation of K10 protein and profilaggrin/filaggrin were
      confirmed by Western analyses. Thus, it appears that the presence of
      intercellular HA in the epidermis acts as a brake upon intracellular events that
      occur during keratinocyte differentiation.

PMID- 15149844
TI  - Epidermal growth factor promotes oligodendrocyte process formation and regrowth
      after injury.
AB  - Oligodendrocytes (OLs) form myelin within the central nervous system and are
      targets in numerous demyelinating diseases and injuries. OLs grown in culture
      maintain the developmental timetable which occurs in vivo and mature into cells
      with a relatively normal phenotype. In this study, cultured cells are used to
      test whether EGF can modulate process formation in OLs both before and after
      transection injury. EGF had no effect on the formation of new processes by OLs at
      any stage of development. To test the effect of EGF on process outgrowth after
      injury, mature OLs were selected and injured by laser transection of a single
      process, then imaged at 24-h intervals for 120 h. EGF promoted the recovery and
      regrowth of injured processes and also significantly increased outgrowth in
      uninjured processes. As well, it increased the number of new sprouts formed by
      OLs after injury. Results suggest that the effects of EGF on process outgrowth
      are a consequence of EGF interaction with a signaling pathway that is
      specifically activated within injured OLs. The potent effect of EGF on OL process
      formation after an injury suggests that modulation of the signaling pathways
      involved might provide a mechanism to promote remyelination.

PMID- 15149845
TI  - Rapid inactivation of alpha-1-proteinase inhibitor by neutrophil specific
      leukolysin/membrane-type matrix metalloproteinase 6.
AB  - Leukolysin/MT6-MMP is a GPI-anchored matrix metalloproteinase (MMP) primarily
      expressed by neutrophils. It is stored in intracellular granules at resting
      state, but rapidly discharged upon stimulations into the extracellular milieu,
      presumably to promote tissue remodeling or destruction. The proteolytic targets
      for leukolysin at the inflammatory sites remain unknown. Here, we show that alpha
      1-proteinase inhibitor, or alpha1-PI, a known protective shield against
      destructive serine proteinases, is a physiological target for leukolysin. We show
      that alpha1-PI failed to accumulate in media conditioned by cells co-expressing
      alpha1-PI and leukolysin. Purified leukolysin cleaves alpha1-PI efficiently at
      the Phe376Leu and Pro381Met bonds and the cleaved alpha1-PI lost its anti
      proteolytic activity against human neutrophil elastase, cathepsin G (CatG) and
      proteinase 3 (PR3). In fact, leukolysin preferentially cleaves alpha1-PI when co
      incubated with other extracellular molecules such as laminin and gelatin.
      Kinetically, leukolysin is more active than two known neutrophil MMPs, MMP8 and
      MMP9, in cleaving and inactivating alpha1-PI. Taken together, these results
      suggest that neutrophils may mediate tissue destruction by deploying leukolysin
      to weaken the alpha1-PI protective shield at inflammatory sites.

PMID- 15149846
TI  - Expression of active plasminogen activator inhibitor-1 reduces cell migration and
      invasion in breast and gynecological cancer cells.
AB  - Urokinase-type (uPA) plasminogen activator is regulated by serine protease
      inhibitors (serpins), especially plasminogen activator inhibitor-1 (PAI-1). In
      many cancers, uPA and PAI-1 contribute to the invasive phenotype. We examined the
      in vitro migration and invasive capabilities of breast, ovarian, endometrial, and
      cervical cancer cell lines compared to their plasminogen activator system
      profiles. We then overexpressed active wild-type PAI-1 and an inactive
      "substrate" P14 form of PAI-1 (T333R) using stable transfection and adenoviral
      gene delivery. We also upregulated endogenous uPA and PAI-1 in these cells by
      treatment with transforming growth factor-beta. Some breast and ovarian cancer
      cell lines with natural expression of uPA, PAI-1, and urokinase receptor showed
      substantial migration and invasion compared to other cell lines that lack
      expression of these proteins. However, overexpression of active wild-type PAI-1,
      but not P14-PAI-1 (T333R), in these cell lines showed reduced migration and
      invasion. Since vitronectin binding by both forms of PAI-1 is equivalent, these
      results imply that PAI-1-vitronectin interactions are less critical in altering
      migration and invasion. Our results show that the in vitro migratory and invasive
      phenotype in these breast and ovarian cancer cell lines is reduced by active PAI
      1 due to its ability to inhibit plasminogen activation.

PMID- 15149847
TI  - Differential effects of the Ski-interacting protein (SKIP) on differentiation
      induced by transforming growth factor-beta1 and bone morphogenetic protein-2 in
      C2C12 cells.
AB  - The transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins
      (BMP) are key regulatory factors that affect many critical cellular events in
      growth and development. Recently, we have shown that the Ski-interacting protein
      (SKIP) can augment TGF-beta signals. Here, we extended these studies by examining
      the biologic consequences of SKIP overexpression on TGF-beta1 and BMP-2 signals
      in C2C12 cells. C2C12 myoblasts differentiate into myotubes when the media is
      depleted of mitogenic factors, and TGF-beta1 inhibits this myotube formation. BMP
      2 not only inhibits the myotube formation, but also induces C2C12 cells to
      differentiate into osteoblasts. Here, we show that SKIP-overexpressing C2C12
      cells treated with TGF-beta1 or BMP-2 displayed no differences in comparison to
      vector control cells in their ability to form myotubes or in the expression of
      the myogenic markers myosin heavy chain-1 and myogenin. Unexpectedly, SKIP
      overexpressing C2C12 cells treated with BMP-2 displayed suppressed expression of
      the induced osteoblast markers alkaline phosphatase, osteocalcin, and the
      transcription factor Runx2. Lastly, SKIP could repress transcription induced by
      BMP-2 in luciferase reporter assays done in C2C12 cells. These data show that
      SKIP has specific inhibitory effects on BMP-2-induced differentiation and
      implicate SKIP to be a novel regulator of the differentiation programming induced
      by TGF-beta signals.

PMID- 15149848
TI  - Consequences of Notch-mediated induction of Jagged1.
AB  - Notch signaling is initiated upon contact of cells expressing Notch receptors
      with those expressing ligands. While examining the dynamic response of NIH 3T3
      cells to cells expressing the Notch ligand Jagged1, we found that Notch signaling
      resulted in increased levels of the ligand Jagged1. Induction of Jagged1 was
      delayed relative to the generation of active Notch and dependent on the
      transcription factor p63. The induced Jagged1 had no apparent autocrine effects
      on Notch signaling but could promote signaling in naive cells. These results
      describe a mechanism through which Notch signaling can be relayed from cell to
      cell.

PMID- 15149849
TI  - Role of the p70(S6K) pathway in regulating the actin cytoskeleton and cell
      migration.
AB  - We have examined the role of endogenous 70-kDa S6 kinase (p70(S6K)) in actin
      cytoskeletal organization and cell migration in Swiss 3T3 fibroblasts.
      Association of p70(S6K) with the actin cytoskeleton was demonstrated by
      cosedimentation of p70(S6K) with F-actin and by subcellular fractionation in
      which p70(S6K) activity was measured in the F-actin cytoskeletal fraction.
      Immunocytochemical studies showed that p70(S6K), Akt1, PDK1, and p85
      phosphoinositide 3-kinase (PI 3-kinase) were localized to the actin arc, a
      caveolin-enriched cytoskeletal structure located at the leading edge of migrating
      cells. Using a phospho-specific antibody to mammalian target of rapamycin (mTOR),
      we find that activated mTOR is enriched at the actin arc, suggesting that
      activation of the p70(S6K) signaling pathway is important to cell migration.
      Using the actin arc to assess migration, epidermal growth factor (EGF)
      stimulation was found to induce actin arc formation, an effect that was blocked
      by rapamycin treatment. We show further that actin stress fibers may function to
      down-regulate p70(S6K). Fibronectin stimulated stress fiber formation in the
      absence of growth factors and caused an inactivation of p70(S6K). Conversely,
      cytochalasin D and the Rho kinase inhibitor Y-27632, both of which cause stress
      fiber disruption, increased p70(S6K) activity. These studies provide evidence
      that the p70(S6K) pathway is important for signaling at two F-actin microdomains
      in cells and regulates cell migration.

PMID- 15149850
TI  - AKT1 drives endothelial cell membrane asymmetry and microglial activation through
      Bcl-xL and caspase 1, 3, and 9.
AB  - Protein kinase B (Akt1) holds a central role for cellular growth, development,
      and survival, but the cellular pathways of Akt1 that prevent inflammatory demise
      in the vascular system remain undefined. Employing a constitutively active form
      of Akt1 (myristoylated Akt1) in endothelial cells (ECs), we demonstrate that Akt1
      not only modulates intrinsic pathways of EC injury that involve genomic DNA
      destruction, but also uniquely regulates extrinsic mechanisms of cellular
      inflammation mediated by phosphatidylserine exposure (PS) and microglial
      activation. Activation of Akt1 is necessary and sufficient to prevent apoptotic
      EC destruction, since inhibition of the phosphatidylinositide-3-kinase pathway as
      well as transfection of ECs with a dominant-negative Akt1 mutant abrogates
      vascular protection. Furthermore, we illustrate that control of microglial
      activation by Akt1 is directly dependent on the modulation of EC membrane PS
      exposure. Akt1 provides a novel capacity to foster EC survival through the
      prevention of cysteine protease degradation of Bcl-x(L) that is intimately linked
      to the specific inhibition of caspase 1-, 3-, and 9-like activities and the
      modulation of mitochondrial membrane potential and cytochrome c release. Our work
      elucidates the critical role of Akt1 during cellular inflammation and identifies
      new downstream targets of Akt1 that may offer therapeutic potential against
      vascular disease.

PMID- 15149851
TI  - Nuclear ERM (ezrin, radixin, moesin) proteins: regulation by cell density and
      nuclear import.
AB  - The highly conserved ERM (ezrin-radixin-moesin) family of proteins function as
      molecular linkers between the actin cytoskeleton and transmembrane receptors. We
      now provide unequivocal evidence that full-length endogenous ezrin and moesin
      also localise to the nucleus in two independent mammalian cell lines. All three
      ERM family members can localise to the nucleus upon exogenous expression of their
      GFP-tagged counterparts, suggesting a common family trend. Furthermore, Dmoesin,
      the Drosophila ERM homologue, is present in the nucleus of an insect cell line
      and can localise to the nucleus when exogenously expressed in MDCK cells. The
      nuclear localisation of endogenous ezrin and moesin is regulated by cell density
      and is resistant to detergent extraction, suggesting tight association with
      nuclear structures. Furthermore, phosphorylation in the actin-binding domain is
      not a prerequisite for nuclear localisation. We have identified a specific
      nuclear localisation sequence, which is conserved and functional in all ERM
      family members, implying specific regulated nuclear import. Although the precise
      nuclear function of the ERM proteins is unknown, these data provide further
      evidence that an increasing number of cytoskeletal components directly link the
      plasma membrane with nuclear events.

PMID- 15149852
TI  - Fibroblasts contribute to the deposition of laminin 5 in the extracellular
      matrix.
AB  - Laminin 5 (alpha3beta3gamma2) is specifically present in the basal lamina
      underneath epithelia with secretory or protective functions, where it is
      essential for anchoring basal epithelial cells to the underlying extracellular
      matrix. Laminin 5 is produced by epithelial cells as a 480-kDa precursor that is
      converted into forms of 440 and 400 kDa. To analyse the processing of laminin 5,
      we have used monolayer and co-cultures of epithelial cells and fibroblasts. The
      processing of the 180-kDa laminin alpha3 chain to 165 kDa in the cell culture
      medium, and to both 165 and 145 kDa polypeptides in the cell layer, are not
      modified by the presence of fibroblasts. In contrast, cleavage of the laminin
      gamma2 chain, occurring in the cell culture medium and in the cell layer, is
      enhanced by the presence of fibroblasts. Further analysis by immunofluorescence
      staining and laser-scanning microscopy reveals that deposited laminin 5 is
      present in a fibroblast-associated filamentous meshwork. Only laminin 5
      containing a fully processed gamma2 chain is present in this fibroblast
      associated fraction. These studies show that, although laminin 5 is a product of
      epithelial cells, fibroblasts contribute to its integration into the
      extracellular matrix architecture.

PMID- 15149853
TI  - VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of
      breast cancer cells in human microvascular endothelial cells.
AB  - Polychlorinated biphenyl (PCB) congeners, a group of worldwide, persistent
      environmental contaminants, are known to cause carcinogenesis and tumor
      promotion, and may also affect the development of cancer metastasis. Because
      vascular endothelial cells create a selective barrier to the passage of cancer
      cells, we hypothesize that specific PCB congeners can disrupt endothelial
      integrity and increase the transendothelial migration of tumor cells. To examine
      this hypothesis, we elucidated the effects of 2,2',4,6,6'-pentachlorobiphenyl
      (PCB 104), a representative of highly ortho-substituted non-coplanar PCB
      congeners, on the endothelial permeability and transendothelial migration of MDA
      MB-231 breast cancer cells. Exposure of human microvascular endothelial cell 1
      (HMEC-1) to PCB 104 induced endothelial hyperpermeability and markedly increased
      transendothelial migration of MDA-MB-231 cells. These effects were associated
      with overexpression of vascular endothelial growth factor (VEGF). PCB 104
      mediated elevation of VEGF expression was induced by phosphatidylinositol 3
      kinase (PI3K) but not affected by co-treatments with antioxidants or the NF
      kappaB inhibitor SN50. In addition, the PI3K-dependent pathway was involved in
      PCB 104-induced activation of AP-1, a transcription factor implicated in the
      regulation of VEGF gene expression. The VEGF receptor (KDR/Flk-1) antagonist
      SU1498 and the PI3K inhibitor LY294002 inhibited PCB 104-induced
      hyperpermeability. These results indicate that PCB 104 may contribute to tumor
      metastasis by inducing VEGF overexpression that stimulates endothelial
      hyperpermeability and transendothelial migration of cancer cells.

PMID- 15149854
TI  - Purification and cell-surface marker characterization of quiescent satellite
      cells from murine skeletal muscle by a novel monoclonal antibody.
AB  - A novel monoclonal antibody, SM/C-2.6, specific for mouse muscle satellite cells
      was established. SM/C-2.6 detects mononucleated cells beneath the basal lamina of
      skeletal muscle, and the cells co-express M-cadherin. Single fiber analyses
      revealed that M-cadherin+ mononucleated cells attaching to muscle fibers are
      stained with SM/C-2.6. SM/C-2.6+ cells, which were freshly purified by FACS from
      mouse skeletal muscle, became MyoD+ in vitro in proliferating medium, and the
      cells differentiated into desmin+ and nuclear-MyoD+ myofibers in vitro when
      placed under differentiation conditions. When the sorted cells were injected into
      mdx mouse muscles, donor cells differentiated into muscle fibers. Flow cytometric
      analyses of SM/C-2.6+ cells showed that the quiescent satellite cells were c-kit
      , Sca-1-, CD34+, and CD45-. More, SM/C-2.6+ cells were barely included in the
      side population but in the main population of cells in Hoechst dye efflux assay.
      These results suggest that SM/C-2.6 identifies and enriches quiescent satellite
      cells from adult mouse muscle, and that the antibody will be useful as a powerful
      tool for the characterization of cellular and molecular mechanisms of satellite
      cell activation and proliferation.

PMID- 15149855
TI  - Upregulated expression of stanniocalcin-1 during adipogenesis.
AB  - Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric protein originally discovered in
      bony fish, where it protects against toxic levels of environmental calcium by
      lowering the uptake of calcium via the gills and by increasing the reabsorption
      of phosphate in the kidney. Here we report expression of STC-1 in mammalian white
      and brown fat tissue. Coexpression of STC-1 and perilipin confirmed the presence
      of STC-1 in mature fat cells. Neoplastic adipocytes in well-differentiated
      liposarcomas also stained for STC-1, while the frequency of STC-1-positive cells
      was lower in high-grade liposarcomas. The kinetics of STC-1 expression during
      adipogenesis was investigated in 3T3-LI cells, which can be induced to adipocyte
      differentiation. Untreated 3T3-L1 cells displayed negligible amounts of STC-1,
      whereas 3T3-L1 cells, treated with an adipogenic cocktail, upregulated the
      expression of STC-1 concomitantly with acquisition of the adipocytic phenotype.
      We have previously reported a high expression of STC-1 in postmitotically
      differentiated neurons and megakaryocytes. We have also shown that expression of
      STC-1 confers increased resistance to hypoxic and oxidative stress in neurons.
      Given this, our findings suggest that STC-1, also in terminally differentiated
      adipocytes, may function as a "survival factor", which contributes to the
      maintenance of the integrity of mature adipose tissue.

PMID- 15149856
TI  - Dystrophin Dp71 is required for neurite outgrowth in PC12 cells.
AB  - To determine the role of Dp71 in neuronal cells, we generated PC12 cell lines in
      which Dp71 protein levels were controlled by stable transfection with either
      antisense or sense constructs. Cells expressing the antisense Dp71 RNA (antisense
      Dp71 cells) contained reduced amounts of the two endogenous Dp71 isoforms.
      Antisense-Dp71 cells exhibited a marked suppression of neurite outgrowth upon the
      induction with NGF or dibutyryl cyclic AMP. Early responses to NGF-induced
      neuronal differentiation, such as the cessation of cell division and the
      activation of ERK1/2 proteins, were normal in the antisense-Dp71 cells. On
      contrary, the induction of MAP2, a late differentiation marker, was disturbed in
      these cells. Additionally, the deficiency of Dp71 correlated with an altered
      expression of the dystrophin-associated protein complex (DAPC) members alpha and
      beta dystrobrevins. Our results indicate that normal expression of Dp71 is
      essential for neurite outgrowth in PC12 cells and constitute the first direct
      evidence implicating Dp71 in a neuronal function.

PMID- 15149857
TI  - The essential role of PKCalpha in the protective effect of heat-shock
      pretreatment on TNFalpha-induced apoptosis in hepatic epithelial cell line.
AB  - During sepsis, hepatic apoptosis occurred, which is associated with inactivation
      of PKCalpha and elevation of tumor necrosis factor-alpha (TNFalpha), an apoptosis
      trigger. Heat shock, accompanied by the increase of heat-shock protein (Hsp72),
      has been shown to exhibit a protective role on cell survival. However, Hsp72 was
      unable to express during sepsis when the apoptosis was markedly increased. We
      hypothesized that hepatic apoptosis during sepsis may be due to the failure to
      induce expression of Hsp72, which is activated by PKC-phosphorylated HSF. This
      study was designed to examine the role of PKCalpha in Hsp72 expression and the
      anti-apoptotic effect of Hsp72 on hepatic epithelial cells by analyzing a
      TNFalpha-induced apoptosis system. The following results were observed: (1) Hsp72
      was highly expressed at 8 h after heat-shock treatment in a clone 9 hepatic
      epithelial cell line; (2) the protein expression of PKCalpha in membrane
      associated fraction was decreased by TNFalpha treatment; (3) the TNFalpha-induced
      cell death, especially apoptosis, was diminished by heat-shock pretreatment; (4)
      in the presence of PKCalpha antisense, which blocks the PKCalpha resynthesis, no
      protective effect of heat-shock pretreatment was observed, and the protein
      expression of Hsp72 was significantly suppressed. These results suggest that
      PKCalpha plays a critical role in the expression of Hsp72, which subsequently
      protects against TNFalpha-induced hepatic apoptosis.

PMID- 15149858
TI  - Membrane localization of v-ErbB is required but not sufficient for ligand
      independent transformation.
AB  - The v-ErbB retroviral oncogene is a transduced, mutated copy of the avian EGF
      receptor gene, and its expression is sufficient to induce tumor formation in
      vivo. The structural alterations that release the oncogenic potential of the v
      ErbB oncogene are similar to EGFR gene mutations described in human tumors. Thus,
      the study of v-ErbB tumor biology offers a useful model through which we can gain
      insight into the mechanism of EGFR-induced malignancies. Despite years of study,
      however, questions remain regarding the domains of v-ErbB required for
      oncogenicity. We sought to clarify the role of the transmembrane domain of v-ErbB
      during transformation using S3-v-ErbB, an acutely transforming retroviral
      oncogene isolated from avian sarcomas. Infection of primary fibroblasts with a
      retroviral vector containing S3-v-ErbB results in the formation of a
      transformation-associated phosphoprotein signaling complex, soft agar colony
      formation, and the rapid induction of highly vascularized sarcomas in vivo. To
      address contribution of the transmembrane domain of S3-v-ErbB during these
      processes, we constructed a mutant version of this oncogene with a precise
      deletion in this domain. Specifically, the S3-v-ErbB-TM- mutant was created
      through an in-frame deletion of the entire transmembrane domain. Primary
      fibroblasts expressing this S3-v-ErbB-TM- mutant fail to form a characteristic
      transformation-associated phosphoprotein complex and do not grow in an anchorage
      independent manner. In addition, day-old chicks injected with a helper
      independent retrovirus expressing the S3-v-ErbB-TM- mutant exhibit only limited
      tumor formation in vivo. These results demonstrate that the transmembrane domain
      and, consequently membrane localization, are essential for S3-v-ErbB-mediated
      transformation.

PMID- 15149859
TI  - The small leucine-rich proteoglycan lumican inhibits melanoma progression.
AB  - Lumican is a member of the small leucine-rich proteoglycan (SLRP) family. It
      contributes to the organisation of the collagen network and plays an important
      role in cell migration and tissue repair. The present study aimed to determine
      the influence of lumican expression on adhesion, anchorage-dependent and 
      independent growth, migration, in vitro invasion and in vivo melanoma growth. For
      that purpose, B16F1 mouse melanoma cells were stably transfected with an
      expression plasmid containing the complete lumican cDNA. Lumican expression by
      tumor cells did not change the proliferative activity of mouse melanoma cells in
      monolayer culture and did not influence either cell adhesion to extracellular
      matrix gel or type I collagen or cell spreading on these substrates. In contrast,
      lumican-transfected cells were characterized by a strong reduction of their
      anchorage-independent proliferation in agarose gel and capacity to invade
      extracellular matrix gel. After subcutaneous injections of transfected B16F1
      cells in syngenic mice, lumican expression significantly decreased subcutaneous
      tumor formation in vivo, with a concomitant decrease of cyclin D1 expression.
      Lumican induced and/or increased the apoptosis of B16F1 cells. The results
      suggest that lumican is involved in the control of melanoma growth and invasion
      and may be considered, like decorin, as an anti-tumor factor from the
      extracellular matrix.

PMID- 15149860
TI  - Intracellular trafficking and degradation of unassociated proalpha2 chains of
      collagen type I.
AB  - Procollagen I is a trimer consisting of two proalpha1(I) chains and one proalpha
      2(I) chain. In certain cases of mild osteogenesis imperfecta, abnormal
      proalpha1(I) chains are degraded very soon after synthesis. As a consequence, the
      cells produce excess proalpha2(I) chains, which cannot form trimers and are not
      secreted. The objective of this work was to determine the intracellular fate of
      unassociated proalpha2(I) chains. Mov13 mouse fibroblasts, which do not
      synthesize proalpha1(I) mRNA, but do produce proalpha2(I) mRNA, were incubated
      with radioactive amino acids using pulse-chase protocols, and proteins were
      analyzed by gel electrophoresis, autoradiography, and Western blotting. Mov13
      cells produced proalpha2(I) chains that were degraded intracellularly within 30
      min. Degradation was inhibited when cells were treated with brefeldin-A, which
      blocks transit from endoplasmic reticulum to Golgi. Fixed cells exposed to
      various immunofluorescence markers and imaged by confocal laser scanning
      microscopy showed that proalpha2(I) chains colocalized with Golgi and lysosome
      markers. Degradation was inhibited and chains were secreted when cells were
      treated with wortmannin, which blocks trafficking to lysosomes. These results
      demonstrate that unassociated proalpha2(I) chains leave the endoplasmic
      reticulum, transit the Golgi, and enter lysosomes where they are degraded.

PMID- 15149861
TI  - Lysophosphatidic acid regulates murine blastocyst development by transactivation
      of receptors for heparin-binding EGF-like growth factor.
AB  - Transient elevation of intracellular calcium (Ca2+(i)) by various means
      accelerates murine preimplantation development and trophoblast differentiation.
      Several G-protein-coupled receptors (GPCRs), including the lysophosphatidic acid
      (LPA) receptor (LPAR), induce Ca2+(i) transients and transactivate the EGF
      receptor (ErbB1) through mobilization of EGF family members, including heparin
      binding EGF-like growth factor (HB-EGF). Because HB-EGF accelerates blastocyst
      differentiation in vitro, we examined whether crosstalk between LPA and HB-EGF
      regulates peri-implantation development. During mouse blastocyst differentiation,
      embryos expressed LPAR1 mRNA constitutively, LPAR2 only in late stage blastocysts
      and no LPAR3. Consistent with a mechanism based on Ca2+(i) signaling, LPA rapidly
      accelerated the rate of trophoblast outgrowth, an index of blastocyst
      differentiation, and chelation of Ca2+(i) with BAPTA-AM blocked LPA stimulation.
      Interfering with HB-EGF signaling through ErbB1 or ErbB4 also attenuated LPA
      stimulation. We established that mouse blastocysts indeed express HB-EGF and that
      LPA induces the transient accumulation of HB-EGF on the embryo surface, which was
      blocked by treatment with either BAPTA-AM or the protein trafficking inhibitor,
      brefeldin A. We conclude that LPA accelerates blastocyst differentiation through
      its ability to induce Ca2+(i) transients and HB-EGF autocrine signaling.
      Transactivation of ErbB1 or ErbB4 by HB-EGF could represent a convergent
      signaling pathway accessed in the trophoblast by stimuli that mobilize Ca2+(i).

PMID- 15149862
TI  - Distinct functions for WRN and TP53 in a shared pathway of cellular response to 1
      beta-D-arabinofuranosylcytosine and bleomycin.
AB  - Mutations in the WRN or the TP53 genes lead to spontaneous genetic instability,
      an elevated risk of tumor formation, and sensitivity to compounds that interfere
      with DNA replication, such as camptothecin and DNA interstrand cross-linking
      drugs. We investigated the hypothesis that WRN and TP53 are involved in cellular
      responses to DNA replication-blocking lesions by exposing WRN deficient and TP53
      mutant lymphoblastoid cell lines (LCLs) to 1-beta-d-arabinofuranosylcytosine
      (AraC) and bleomycin. Loss of WRN or TP53 function resulted in induction of
      apoptosis and lesser proliferative survival in response to AraC and bleomycin.
      WRN and TP53 operate in a shared DNA damage response pathway, since in cells in
      which TP53 was inactivated by SV-40 transformation, no difference in AraC and
      bleomycin sensitivity was found regardless of WRN status. In contrast to TP53
      mutant LCLs, WRN-deficient cells showed unaffected cell cycle arrest after AraC
      and bleomycin exposure, which indicates that WRN is not involved in DNA damage
      activated cell cycle arrest. Neither WRN nor TP53 deficiency affected cellular
      recovery from exposure to AraC and bleomycin, which disagrees with a direct role
      in repair of these DNA lesions. Our results indicate that WRN and TP53 perform
      different functions in a shared DNA damage response pathway.

PMID- 15149863
TI  - Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer
      cells by suppressing drug-induced apoptosis.
AB  - Ribosomal proteins (RP) S13 and RPL23 were previously identified as two
      upregulated genes in a multidrug-resistant gastric cancer cell line SGC7901/VCR
      compared to its parental cell SGC7901 by differential display PCR. The aim of
      this study was to explore the roles of RPS13 and RPL23 in multidrug resistance
      (MDR) in gastric cancer cells. RPS13 and RPL23 were genetically overexpressed in
      SGC7901 cells, respectively. Either RPS13 or RPL23 enhanced resistance of SGC7901
      cells to vincristine, adriamycin, and 5-fludrouracil. RPL23 also enhanced
      resistance of SGC7901 cells to cisplatin. Overexpression of either RPS13 or RPL23
      did not alter the population doubling time, [3H]leucine incorporation, and
      intracellular adriamycin accumulation of SGC7901 cells. However, either RPS13 or
      RPL23 could protect SGC7901 cells from undergoing vincristine-induced apoptosis.
      Western blot analysis revealed that both RPS13 and RPL23 significantly increased
      the expression level of Bcl-2 and Bcl-2/Bax ratio in SGC7901 cells. In addition,
      overexpression of RPL23 enhanced glutathione S-transferase (GST) activity and
      intracellular glutathione content in SGC7901 cells. Together, this work
      demonstrates that either RPS13 or RPL23 can promote MDR in gastric cancer cells
      by suppressing drug-induced apoptosis, and that RPL23 may also promote MDR in
      gastric cancer cells through regulation of glutathione S-transferase-mediated
      drug-detoxifying system.

PMID- 15149864
TI  - Signal transduction pathways that contribute to CDK1/cyclin B activation during
      the first mitotic division in sea urchin embryos.
AB  - In sea urchins, fertilization triggers a rapid rise in protein synthesis
      necessary for activation of CDK1/cyclin B, the universal cell cycle regulator. It
      has been shown that FRAP/mTOR is required for eIF4E release from the
      translational repressor 4E-BP, a process that occurs upstream of de novo cyclin B
      synthesis. Here, we investigate whether PI 3-kinase acts independently or
      upstream from FRAP/mTOR in the signal transduction pathway that links
      fertilization to the activation of the CDK1/cyclin B complex in sea urchin egg.
      We found that wortmannin, a potent inhibitor of PI 3-kinase, partially inhibited
      the global increase in protein synthesis triggered by fertilization. Furthermore,
      wortmannin treatment induced partial inhibition of cyclin B translation triggered
      by fertilization, in correlation with an intermediate effect of the drug on 4E-BP
      degradation and on the dissociation of the 4E-BP/eIF4E complex induced by
      fertilization. Our results presented here suggest that PI 3-kinase activity is
      required for completion of mitotic divisions of the sea urchin embryo. Incubation
      of eggs with wortmannin or microinjection of wortmannin or LY 294002 affects
      drastically mitotic divisions induced by fertilization. In addition, we found
      that wortmannin treatment inhibits dephosphorylation of the tyrosine inhibitory
      site of CDK1. Taken together, these data suggest that PI 3-kinase acts upstream
      of at least two independent targets that function in the CDK1/cyclin B activation
      triggered by fertilization of sea urchin oocytes. We discuss the significance of
      these results concerning the cascade of reactions that impinge upon the
      activation of the CDK1/cyclin B complex that follows sea urchin oocyte
      fertilization.

PMID- 15149866
TI  - Adiponectin and atherosclerotic disease.
AB  - Adiponectin has been identified as one of the "adipocytokines" that are derived
      only from adipose tissue, and are abundantly present in circulating blood.
      Adiponectin has protective actions in the initiation and progression of
      atherosclerosis through anti-inflammatory and anti-atherogenic effects.
      Adiponectin levels are decreased in obesity, type 2 diabetes, and patients with
      coronary artery disease (CAD). Adiponectin levels were negatively correlated with
      the CRP levels in patients with CAD. Adiponectin plays a crucial role in the
      association between obesity, type 2 diabetes, and insulin resistance. Mechanisms
      explaining the relationship between adiponectin and insulin resistance suggest
      that adiponectin and tumor necrosis factor (TNF)-alpha inhibited each other's
      expression and production in adipocytes. Thiazolidinediones, which are insulin
      sensitizing agents, increased the production of adiponectin through directly
      enhancing its gene expression. The C-terminal globular domain of adiponectin may
      play a central role in the protective effects against atherosclerosis.
      Adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) are expressed ubiquitously in
      most organs, especially in skeletal muscle in AdipoR1, and liver in AdipoR2. With
      the prospect of future basic and clinical research on the molecular structure
      receptor relationship, adiponectin could become a promising target for future
      investigations in reducing the morbidity and mortality of atherosclerotic
      disease.

PMID- 15149865
TI  - Impact of cholesterol depletion on shape changes, actin reorganization, and
      signal transduction in neutrophil-like HL-60 cells.
AB  - Stimulation of neutrophils with chemotactic peptide induces actin reorganization,
      formation of actin-rich protrusions, and development of polarity. Shape changes
      and actin polymerization can also be induced by phorbol ester-mediated direct
      activation of protein kinase C (PKC). We have investigated the role of
      cholesterol in stimulus-dependent motile events and in activation of signaling
      pathways in neutrophil-like differentiated HL-60 cells. Depletion of plasma
      membrane cholesterol using methyl-beta-cyclodextrin (MbetaCD) prevented
      chemotactic peptide and phorbol ester-induced shape changes and increases in
      cytoskeletal actin. Cholesterol depletion almost completely suppressed
      chemotactic peptide-mediated activation of p42/44 mitogen-activated protein
      kinase (MAPK). Phosphorylation of protein kinase B on Thr-308, which is
      indicative of activation of phosphatidylinositol 3-kinase, was in contrast only
      partially inhibited. Stimulus-mediated membrane recruitment of different PKC
      isoforms was differentially affected by treatment of cells with MbetaCD. Membrane
      recruitment of PKCalpha induced by chemotactic peptide or phorbol ester was
      suppressed, whereas that of PKCbetaII was only partially affected. Membrane
      association of PKCdelta was almost insensitive to cholesterol depletion. In
      summary, our results implicate an important role of cholesterol-containing lipid
      microdomains (rafts) especially in chemotactic peptide-induced activation of MAPK
      pathways and in chemotactic peptide- and phorbol ester-mediated activation of
      PKCalpha.

PMID- 15149867
TI  - Disseminated intravascular coagulation.
AB  - The diagnosis of disseminated intravascular coagulation (DIC) was initially based
      on the detection of microthrombi. Current diagnosis involves laboratory
      assessment of hemostatic abnormalities although additional studies may often be
      necessary. DIC is characterized by hypercoagulability and hyperfibrinolysis and
      is caused by high offense factors or low defense factors. DIC is divided two
      stages: overt-DIC and non-overt-DIC. The diagnosis of overt-DIC state is based on
      the criteria developed by the International Society of Thrombosis Haemostasis in
      conjunction with the Japanese Ministry Health and Welfare. However, no criteria
      are currently available for the diagnosis of non-overt DIC. Although
      scientifically supported modalities for treatment of DIC are few, the use of
      activated protein C (APC) and low-molecular-weight heparin appear to hold
      promise.

PMID- 15149868
TI  - Polyamines as clinical laboratory tools.
AB  - Since their discovery by Antoni van Leeuwenhoek in 1678 until the recent
      development of transgenic mice expressing proteins altering polyamine levels in a
      tissue-specific manner, polyamines have been the object of intense research
      efforts which have shed light on several biological and pathological processes.
      From the discovery of a particular form of proteasome regulation of the
      catabolism of the key regulatory enzyme in their synthetic pathway, to the
      experimental cancer treatment or prevention with polyamine antagonists or
      inhibitors of the latter enzyme, a whole spectrum of interests can be revealed.
      Still, many aspects of their functions remain elusive and difficulties inherent
      in their analysis, which relies on sophisticated high-performance liquid
      chromatographic (HPLC) methods, and the lack of standardization; have hampered
      the transit from the research realm to the standard clinical laboratory domain.
      Their assay in biological fluids has been used for cancer diagnosis and for
      monitoring anticancer treatment. In this article, we attempt to provide an
      overview of polyamine structure, nutritional value, metabolism, and physiological
      roles. Next, we will summarize the main analytical methods on which we count, and
      finally we will address their role in diagnosis of cancer as well their proposed
      role as antioxidant and antiglycation agents.

PMID- 15149869
TI  - Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers
      of inflammation.
AB  - The EF-hand homolog family of S100 proteins comprises the largest group of
      calcium-binding proteins. Within this S100 family, the phagocyte-specific calcium
      binding proteins are pro-inflammatory molecules expressed and secreted by
      phagocytes, which play a pivotal role within the innate immune system. Although
      the exact biological functions of these proteins still remain to be defined in
      greater detail, there is evidence that they are involved in a pro-inflammatory
      axis associated with various inflammatory conditions. The three members of this
      group, S100A8, S100A9 and S100A12 are overexpressed at local sites of
      inflammation. High concentrations are found in synovial fluid, sputum, stool and
      blood plasma/serum during inflammation. Both the S100A8/S100A9 complex and
      S100A12 have been proven to be useful as diagnostic markers of inflammation
      especially in non-infectious inflammatory diseases such as arthritis, chronic
      inflammatory lung and bowel disease. They indicate phagocyte activation more
      sensitively than conventional parameters of inflammation. As a consequence, there
      is a strong correlation to the inflammation of various acute and chronic
      disorders, making these proteins sensitive parameters for the monitoring of
      disease activity and response to treatment in individual patients. The phagocyte
      specific S100 proteins are able to indicate minimal residual inflammation, which
      is not detected by other diagnostic tests, and they may even be prospective
      markers for the outcome of patients. In this review, pro-inflammatory functions
      of S100 proteins and their usefulness as biomarkers of inflammation are
      presented.

PMID- 15149870
TI  - The effect of estrogen on serum nitric oxide concentrations in normotensive and
      DOCA Salt hypertensive ovariectomized rats.
AB  - BACKGROUND: Cardiovascular disease (CVD) is less prevalent in premenopausal women
      and women receiving estrogen replacement therapy (ERT) than in postmenopausal
      women or men. It proposed that the cardiovascular effects of estrogen are
      mediated, at least in part, through the ability of estrogen to increase nitric
      oxide (NO) synthesis. This study investigated the effect of estrogen on serum NO
      concentrations in normotensive and deoxycorticostrone acetate (DOCA) Salt
      hypertensive ovariectomized rats. METHODS: Forty-eight female rats were
      ovariectomized and randomly divided into six groups. Hypertension was induced by
      DOCA Salt method. DOCA was injected 30 mg/kg of body weight subcutaneously, twice
      a week with NaCl 1% instead of tap water for drinking throughout the treatment
      period. Estradiol valerate (Es) was injected i.m. once a week. The groups were as
      follows: (2) DOCA (4 weeks) and DOCA+Es (6 weeks), (22) DOCA (10 weeks), (222)
      normal saline (N/S) (4 weeks)+Es (6 weeks), (2V) N/S (10 weeks), (V) DOCA (4
      weeks), and (V2) N/S (4 weeks). Serum NO concentrations were measured in groups
      1, 3 and 4 before and after treatment. Other groups were used as control.
      RESULTS: Results showed that in normotensive animals, serum NO concentrations
      were increased after estrogen treatment significantly (90.20 +/- 18.67 vs. 19.11
      +/- 1.78 micromol/l) (p < 0.05). Also, estrogen increased serum NO concentrations
      in DOCA Salt hypertensive rats (73.54 +/- 22.55 vs. 36.94 +/- 10.73 micromol/l)
      (p = 0.06). CONCLUSION: Estrogen can increase serum NO concentrations in
      normotensive and DOCA Salt hypertensive animals and it may be important in
      cardiovascular effects of estrogen.

PMID- 15149871
TI  - Reliable genotyping of the coagulation Factor XIII-A Leu34 variants.

PMID- 15149872
TI  - The effects of hormone replacement therapy combined with vitamins C and E on
      antioxidants levels and lipid profiles in postmenopausal women with Type 2
      diabetes.
AB  - BACKGROUND: Recent studies have demonstrated that oxidative modification of low
      density lipoprotein (LDL) involving the formation of lipid peroxides (MDA),
      exerts several biological effects that may contribute to the onset and
      progression of cardiovascular diseases in postmenopausal women with Type 2
      diabetes (DPMW). Therefore, the aim of our study was to evaluate the effect of
      hormone replacement therapy (HRT), vitamin C and E (VCE) treatments on lipid
      profiles, glucose and MDA levels as well as antioxidant vitamins and enzymes in
      plasma and red blood cells (RBC) in diabetic or non-diabetic postmenopausal women
      (PMW). METHODS: Oral HRT and VCE supplementation for 6 weeks were compared with
      HRT treatment in 40 non-diabetic PMW and 40 DPMW. RESULTS: In the 40
      postmenopausal women (PMW) and 20 postmenopausal women with DPMW who received
      oral HRT and 20 DPMW who received HRT plus VCE, there was a significant fall in
      MDA, total cholesterol, LDL-cholesterol and triglyceride values. Glycated
      haemoglobin (HbA1c) in the DPMW was significantly improved with oral HRT and VCE
      although no significant change in white blood cell counts, vitamin A and HDL
      values occurred. Additionally, a fall in plasma glucose, HbA1c and platelet
      values also occurred in the PMW and DPMW groups by oral HRT and VCE treatments.
      There was a significant increase in plasma vitamin E and beta-carotene
      concentrations, catalase, glutathione peroxidase and reduced glutathione levels
      in RBC and plasma in DPMW by treatments with HRT and/or VCE. CONCLUSIONS: Daily
      VCE and HRT administrations both in PMW and DPMW seem to produce significant
      improvement in antioxidants concentrations, and the metabolic control of lipids
      and glucose. The HRT and VCE supplementations may strengthen the antioxidant
      defense system due to reducing blood glucose and lipid metabolites, and they may
      play a role in preventing cardiovascular diseases in postmenopausal women with
      Type 2 diabetes.

PMID- 15149873
TI  - Cardiac troponin T content in heart and skeletal muscle and in blood samples from
      ApoE/LDL receptor double knockout mice.
AB  - BACKGROUND: The isolated perfused mouse heart is a useful experimental model, and
      cardiac troponin T (cTnT) in coronary effluent may be a sensitive marker of
      myocardial damage. In recent years, the apolipoprotein E/low-density lipoprotein
      receptor double knockout (apoE/LDLr KO) mice have become valuable tools in
      atherosclerosis research. The aim of the study was to validate measurements of
      cTnT in heart, skeletal muscle, and serum of apoE/LDLr KO mice. METHODS: Wild
      type C57BL/6J mice were fed with standard diet, and apoE/LDLr KO mice were fed an
      atherogenic diet. Blood was sampled from the jugular vein or the thoracic cavity.
      Heart and femoral skeletal muscle were sampled and homogenized. cTnT was measured
      with the third-generation cTnT assay (Troponin T STAT) on Elecsys 2010
      immunoassay analyser (Roche Diagnostics). RESULTS: Median serum cTnT in samples
      from the thoracic cavity of C57BL/6J mice was about 20-90 times higher, and from
      ApoE/LDLr KO mice about 30 times higher than serum cTnT in samples from the
      external jugular vein. There was no difference in cTnT content (microg cTnT/g
      heart muscle) in hearts from C57BL/6J and apoE/LDLr KO mice. The median cTnT
      content in skeletal muscle was less than 0.1% of the cTnT content in heart
      muscle. CONCLUSION: There is no difference in cTnT content of heart muscle
      comparing C57BL/6J and ApoE/LDLr KO mice, which have larger hearts. Sampling from
      the thoracic cavity causes unacceptably high cTnT levels. Serum cTnT in samples
      from the jugular vein is only slightly elevated. Elevated baseline levels of cTnT
      in mice are not caused by troponin T from skeletal muscle.

PMID- 15149874
TI  - Detection of bone marrow infiltration of lymphoma cells by fluorescence in situ
      hybridization.
AB  - BACKGROUND: It is sometimes difficult to detect the bone marrow infiltration of
      lymphoma cells, because lymphoma cells are not distinguishable from normal
      lymphocytes due to the similarity of their phenotype. METHODS: Bone marrow
      involvement of 17 samples of 15 patients with follicular lymphoma, whose lymphoma
      cells were confirmed to harbor the translocation of chromosome14q32, were
      examined by microscopic analysis of bone marrow smear and biopsy, flow
      cytometorical analysis (FCM), chromosomal analysis of G-banding and fluorescence
      in situ hybridization (FISH). FISH was performed using a probe, which detects the
      split of IGH gene on 14q32. RESULTS: The positivity of FISH was highest among
      these methods and FISH was able to detect the bone marrow involvement in one case
      who was defined as negative by bone marrow biopsy. CONCLUSIONS: FISH can be used
      for detection of bone marrow involvement of malignant lymphoma that carries
      chromosomal rearrangement involving 14q32.

PMID- 15149875
TI  - Removal of intravenous Intralipid in patients with familial hypercholesterolemia
      during inhibition of cholesterol absorption and synthesis.
AB  - BACKGROUND: While plant stanols are known to upregulate low density lipoprotein
      (LDL) receptors, we studied the effects of plant stanol (STA) and sterol (STE)
      ester spreads on triglyceride-rich lipoprotein (TRL) removal in statin-treated
      patients with familial hypercholesterolemia (FH) using intravenous Intralipid
      squalene fat tolerance test. METHODS: Five patients consumed STA and STE in a
      randomized, crossover study for 4 weeks. TRL removal was studied at baseline and
      at the end of both periods. Serum, chylomicron (CM), and very low density
      lipoprotein lipids, squalene, and plant sterols were measured. RESULTS: LDL
      cholesterol was decreased by both spreads (15-16%, p<0.05). Plant sterol
      concentrations were doubled in serum and CM by STE vs. STA. After the injection
      of Intralipid, CM squalene and sitosterol, but not triglycerides (TG), reached
      higher peak levels (and area under the incremental curve (AUIC) of squalene) by
      both spreads than at baseline. Despite different plant sterol concentrations by
      STE vs. STA, the incremental curves for plant sterols were similar by the
      spreads. CONCLUSIONS: Despite the retarded removal of TRL lipids by STA and STE
      in the statin-treated subjects with FH, improvement of the fasting lipid profile
      was suggested important in consideration of combination of cholesterol absorption
      inhibitor with statins even in FH.

PMID- 15149877
TI  - Correlation of surrogate markers of Gaucher disease. Implications for long-term
      follow up of enzyme replacement therapy.
AB  - BACKGROUND: The excessive storage of cellular debris in the lysosomal storage
      disorders triggers a variety of cellular responses. Some of these responses are
      maladaptative and result in the pathology of these diseases. To some extent,
      cellular responses are specific to the stored material, which influences the
      pathophysiology of the disease and results in some of its characteristic
      features. METHODS: A large body of data has been collected for three biochemical
      (surrogate) markers of Gaucher Disease: angiotensin converting enzyme (ACE),
      tartrate-resistant acid phosphatase (TRAP) and chitotriosidase (CHITO) using
      currently available enzyme analysis. Follow up data was gathered in a group of 18
      patients. RESULTS: The three markers are correlated between each other and are
      useful indicators of the disease progress and its response to enzyme replacement
      therapy (ERT). Retrospective analysis of clinical records and comparison of
      chitotriosidase values with the baseline Severity Score Index (SSI) allowed
      prediction of the response patterns for this marker when long-term ERT (>24
      months) was evaluated. CONCLUSIONS: The less severely affected patients are more
      likely to normalize their chitotriosidase activities after long term ERT.

PMID- 15149876
TI  - Performance characteristics of a recombinant enzymatic cycling assay for
      quantification of total homocysteine in serum or plasma.
AB  - BACKGROUND: Homocysteine is an amino acid that has been linked to an increased
      risk of coronary artery disease and stroke. A recombinant enzymatic cycling assay
      for homocysteine was evaluated using a Roche Modular Analytics P800 chemistry
      analyzer. METHODS: Bound homocysteine is released by disulfide reduction and
      combined with serine to form L-cystathionine that is degraded by cystathionine
      beta-lyase into homocysteine, pyruvate, and ammonia. Pyruvate is converted to
      lactate and the amount of NAD+ produced is directly proportional to the
      concentration of homocysteine. The limit of detection (LOD), linearity,
      imprecision, method comparison, reference interval and susceptibility to common
      interferences were assessed. RESULTS: The limit of detection was 0.31 micromol/l.
      The method was linear from 1 to 100 micromol/l with a maximum deviation from the
      target concentration of <10%. The total imprecision was <5.4% for homocysteine
      concentrations between 11.4 and 39.4 micromol/l. Method comparison was performed
      using an immunoassay on the ADVIA Centaur as the comparison method. Deming
      regression analysis gave a slope of 1.00, intercept of -0.75 and r=0.992. The
      mean bias relative to the ADVIA Centaur method was -0.9 micromol/l with limits of
      agreement of -5.0 and +3.5 micromol/l. The reference interval was 4.7 to 12.7
      micromol/l. CONCLUSIONS: This enzymatic assay for homocysteine provides
      acceptable performance on the Modular Analytics P800 analyzer.

PMID- 15149878
TI  - Plasma purine nucleoside phosphorylase in cancer patients.
AB  - BACKGROUND: Purine nucleoside phosphorylase (PNP) is the purine salvage enzyme
      that converts guanosine to guanine and inosine to hypoxanthine. METHODS: 279
      samples from patients with differing cancers were collected during treatment at
      both pre- and post-dose stages for plasma PNP activity and compared with a normal
      population. RESULTS: Normal plasma PNP activity was found to be 3.2+/-1.4 U/l
      (n=55) as compared with the cancer patients (pre-dose 12.3+/-7.4 U/l [n=215] and
      post-dose 11.2+/-5.9 U/l [n=64]). Levels of plasma PNP did not differ greatly
      between the different cancer types but were on average four times greater than
      that found in the reference population.

PMID- 15149880
TI  - A high performance liquid chromatographic method for the measurement of total
      carnitine in human plasma and urine.
AB  - Total carnitine in plasma and urine can be measured by high performance liquid
      chromatography (HPLC) using the novel fluorescent derivatisation reagents 6'
      methoxynaphthacyl trifluoromethanesulfonate and 2'-phenanthrenacyl
      trifluoromethanesulfonate. Sample preparation for total carnitine analysis
      involves: extraction of plasma and urine in methanol, the optional addition of
      serine betaine as an internal standard, saponification of acyl carnitines with
      calcium hydroxide, followed by derivatisation with 6'-methoxynaphthacyl
      trifluoromethanesulfonate or 2'-phenanthrenacyl trifluoromethanesulfonate. The
      derivatives were separated using an alumina column and measured by fluorescence
      detection. The coefficient of variation was below 5% using internal standard
      calibration, and recoveries of acyl carnitines after saponification were over
      90%. The total carnitine method was shown to be linear at biological levels for
      plasma (over the range 30-130 micromol/l) and urine (over the range 80-180
      micromol/l). Advantages of this method include good precision, accuracy and
      linearity, the use of fluorescence to gain sensitivity, the small sample volume
      required and a relatively low sample preparation time.

PMID- 15149879
TI  - Effects of resveratrol on the expression of a panel of genes interacting with the
      BRCA1 oncosuppressor in human breast cell lines.
AB  - BACKGROUND: trans-Resveratrol, or 3,5,4'trihydroxy-trans-stilbene, is a
      polyphenolic compound that seems to provide a protective effect against several
      types of cancer, notably breast cancer. Through its phytoestrogenic properties it
      regulates the expression of hormone-dependent genes, such as the oncosuppressor
      BRCA1, in breast cells. This gene is involved in the majority of hereditary
      breast cancer, as well as sporadic cancers. METHODS: We used three human breast
      tumor cell lines (HBL100, MCF7 and MBA-MB-231) and one breast cell line (MCF10a)
      derived from a fibrocystic disease to study in vitro the effect of resveratrol on
      the transcription of a group of genes whose proteins interact in different
      pathways with BRCA1. BRCA1, BRCA2, ER alpha, ER beta, p53, p21(waf1/cip1),
      CBP/P300, RAD51, pS2 and Ki67 mRNA were quantified using real-time quantitative
      RT-PCR with an ABI 7700 apparatus. RESULTS: Resveratrol modulated the expression
      of these genes in a pattern dependent on the status of alpha and beta estrogen
      receptors. These results show that resveratrol regulates gene expression via the
      estrogen receptor pathway and also an undetermined pathway. CONCLUSION: Thus,
      resveratrol seems to have an effect on breast tumor cell lines, on a fibrocystic
      cell line by affecting several factors regulating the function of BRCA1.

PMID- 15149881
TI  - Cytochemical and biochemical detection of intracellularly accumulated sialyl
      glycoconjugates in sialidosis and galactosialidosis fibroblasts with Macckia
      amurensis.
AB  - BACKGROUND: To clarify the pathogenesis of and evaluate experimental therapeutic
      trials for lysosomal diseases, effective tools for the detection of
      intracellularly accumulated materials are required. METHODS: We examined a series
      of lectins for staining and blotting of the accumulated glycoconjugates in
      sialidosis and galactosialidosis. RESULTS: Lysosomally accumulated sialyl
      glycoconjugates were successfully detected in cultured fibroblasts from patients
      with these diseases by means of staining and blotting with Macckia amurensis
      (MAM). CONCLUSIONS: This procedure is sensitive and easy, and will be useful not
      only for biochemical and diagnostic analyses, but also for therapeutic evaluation
      in these diseases.

PMID- 15149882
TI  - Determination of reference intervals for serum creatinine, creatinine excretion
      and creatinine clearance with an enzymatic and a modified Jaffe method.
AB  - OBJECTIVES: The aim of this study was to determine the reference intervals for
      serum creatinine, the renal creatinine output and the creatinine clearance (CrCl)
      with two new methods for accurate creatinine determination. METHODS: The
      reference population consisted of 252 healthy subjects (127 males and 125
      females) at the age between 18 and 74 years, median 27. Urine was collected for
      exactly 24 h. Creatinine in serum and urine was measured with an enzymatic assay
      ("Creatinine Plus") and a modification of the kinetic Jaffe reaction, named
      "Jaffe compensated". RESULTS: Reference values for serum creatinine were almost
      identical to previously published ones obtained with the same methods: 0.73-1.18
      and 0.55-1.02 mg/dl for males and females, respectively, with the enzymatic, 0.72
      1.16 and 0.55-0.96 mg/dl with the compensated Jaffe method (Jcomp). CrCl values
      were normally distributed and showed no gender difference in contrast to some
      previous studies. The reference interval for the entire group was found to be 66
      143 ml/min with the enzymatic assay and 71-151 ml/min with the chemical one.

PMID- 15149883
TI  - Post-dialysis retention of blood lipoproteins and apolipoproteins in patients
      with end-stage renal disease on maintenance haemodialysis in Kuwait.
AB  - BACKGROUND: The commonest cause of death in patients with end-stage renal disease
      (ESRD) on maintenance haemodialysis (MHD) is coronary heart disease (CHD). It has
      been suggested that dyslipidaemia, an important CHD risk factor, may be worsened
      by dialysis. This study evaluated changes in blood lipoproteins and
      apolipoproteins after dialysis in ESRD patients on MHD. METHODS: The subjects
      were 57 (20 M, 37 F; 24 diabetic, 33 nondiabetic) patients with ESRD, aged 21-73
      years, undergoing MHD at a major Dialysis Unit in Kuwait. Pre- and post-dialysis
      non-fasting blood samples were collected from each subject on the same day, and
      analyzed for plasma glucose, urate, triglycerides (TG), total cholesterol (TC),
      HDL, LDL and apolipoprotein (apo) A1 and B. Pre- and post-dialysis levels for
      each of the analytes were compared for the diabetic and non-diabetic subgroups of
      patients and linear correlations sought between Delta values (corresponding to
      differences between pre- and post-dialysis levels) of the lipoproteins and
      apolipoproteins. RESULTS: There was a general trend towards significant increases
      in post-dialysis TC, HDL, LDL, and non-HDL levels in both sub-groups, and
      additionally for the non-diabetic, TG, apo A1 and apo B. The pre- to post
      dialysis increases were essentially similar for the diabetic and non-diabetic
      groups-Diabetic: TC 14%, HDL 25%, LDL 19%, non-HDL 16%, apo A1 14%, apo B 10%;
      Non-diabetic: TC 20%, TG 29%, HDL 25%, LDL 26%, non-HDL 21%, apo A1 14%, apo B
      14%. Generally, there were significant correlations between Delta values for the
      lipoproteins and apolipoproteins (r, 0.50-0.92) in both groups. CONCLUSION:
      Levels of atherogenic lipoproteins increase post-dialysis in diabetic and non
      diabetic patients with ESRD and the changing levels of these lipoproteins
      correlate significantly with corresponding changes in levels of apolipoproteins.
      The increase in lipid levels is therefore related to retention of apo A1 and B
      with each dialysis. We speculate that, with repeated dialysis, dyslipidaemia may
      get progressively worse and further accentuate CHD risk.

PMID- 15149884
TI  - Serum cystatin C in patients with head and neck carcinoma.
AB  - BACKGROUND: The balance between proteinases of various classes and their
      inhibitors was found to be of critical importance for local invasion and
      metastasizing of tumor cells. The aim of the present study was to determine the
      changes in the serum cystatin C concentration in patients with squamous cell
      carcinoma of the head and neck. METHODS: In the sera of 34 patients with squamous
      cell carcinoma of the head and neck, the concentration of cysteine proteinase
      inhibitor cystatin C was determined using ELISA. The serum samples were collected
      at diagnosis (group A) and 7 to 407 days (median, 59 days) after the therapy
      (group B). The sera of 30 healthy blood donors served as controls (group C).
      RESULTS: A significant increase in the median concentration of cystatin C was
      found in the patients' sera (group A: 573 ng/ml, P<0.0001; group B: 551 ng/ml,
      P<0.0001) compared to control group C (320 ng/ml), whereas no difference was
      observed between groups A and B (P>0.05). Cystatin C concentrations in the sera
      of group A correlated with the site of primary tumor (P=0.035), being higher in
      the patients with non-laryngeal tumors (658 ng/ml) than in those with larynx
      primaries (529 ng/ml). There was a significant trend (RS=-0.535, P=0.049) towards
      lower cystatin C concentrations with an increasing time delay in post-treatment
      serum sampling (group B), which was observed in the patients with no relapse of
      the disease and a sampling later than 45 days after the completion of therapy.
      CONCLUSIONS: These results add to the knowledge of the role of cystatin C in
      invasive behavior of squamous cell carcinoma of the head and neck, and suggest
      its potential role as a tumor marker in this particular type of cancer.

PMID- 15149885
TI  - Activation of PAF receptor by oxidised LDL in human monocytes stimulates
      chemokine releases but not urokinase-type plasminogen activator expression.
AB  - BACKGROUND: We investigated whether the increase of urokinase-type plasminogen
      activator (uPA) monocyte expression and chemokine releases induced by oxidised
      low density lipoproteins (LDL), which participate to vascular tissue remodeling
      and to atherosclerotic plaque rupture, involved proinflammatory phospholipid
      products having platelet-activating factor (PAF)-like activity via the PAF
      receptor pathway. METHODS: uPA monocyte expression was stimulated by either
      copper ions-oxidised or O2*-/HO* free radical-oxidised LDL. The effects of PAF
      and oxidised LDL on the production of monocyte chemoattractant protein-1 and
      interleukin-8 were also examined. RESULTS: Synthetic PAF significantly enhanced
      chemokine releases (P<0.001) without modifying uPA expression. Copper-oxidised
      LDL, which exhibit a higher content in lysophosphatidylcholines than free radical
      oxidised LDL, induced a significantly higher enhancement in uPA expression
      (P<0.05). By contrast, free radical-oxidised LDL were more efficient than copper
      oxidised LDL to increase chemokine releases (P<0.01). Oxidised LDL-enhanced uPA
      expressions were not altered by the PAF-receptor antagonist SR27417, whereas
      increases in chemokine releases induced by oxidised LDL and by PAF were
      abolished. PAF-acetylhydrolase activity was rapidly and largely inhibited in free
      radical-oxidised LDL when compared to copper-oxidised LDL, suggesting that free
      radical-oxidised LDL would contain a higher content in PAF-like products than
      copper-oxidised LDL. CONCLUSION: Our results indicated that PAF-like oxidation
      products are responsible for the monocyte chemokine releases, but did not
      contribute to the enhanced monocyte uPA expression by oxidised LDL.

PMID- 15149886
TI  - Coenzyme Q10 changes are associated with metabolic syndrome.
AB  - BACKGROUND: The purpose of this study was to determine whether coenzyme Q10 (CoQ)
      concentrations and redox status are associated with components of the metabolic
      syndrome. METHODS: This is a cross-sectional survey of 223 adults (28-78 years),
      who were drawn from the ongoing Princeton Follow-up Study in greater Cincinnati.
      Individuals were assessed for measures of fatness, blood pressure, glucose, lipid
      profiles, C-reactive protein (CRP), reduced CoQ (ubiquinol), oxidized CoQ
      (ubiquinone), total CoQ and CoQ redox ratio (ubiquinol/ubiquinone). RESULTS:
      After adjusting for age, sex and race, we found that total CoQ, ubiquinol and CRP
      levels are significantly increased in metabolic syndrome. Comparison of minimal
      risk and high-risk metabolic syndrome groups indicates an increased CoQ redox
      ratio in the high risk group (p<0.05). Step-wise logistic regression analysis,
      using age, sex, race, (ln)CRP, total cholesterol, LDL, ubiquinol, ubiquinone and
      total CoQ as predictors, shows that only age (p=0.001), total CoQ adjusted for
      plasma lipids (p<0.0001) and (ln)CRP (p<0.005) were significant predictors of
      metabolic syndrome. CONCLUSIONS: The presence of metabolic syndrome components
      are associated with increased plasma total CoQ and ubiquinol concentrations after
      adjusting for age, sex and race. An increase in CoQ redox ratio may indicate a
      gender-specific adaptive response to oxidative stress in females, but not males.

PMID- 15149887
TI  - A study of urinary myo-inositol as a sensitive marker of glucose intolerance.
AB  - BACKGROUND: We assessed the possibility of using myo-inositol as a marker of
      glucose intolerance. METHODS: We measured urinary myo-inositol enzymatically
      before and 2 h after a 75-g oral glucose tolerance test in 564 volunteers, who
      were divided into four groups [normal glucose tolerance (NGT), impaired fasting
      glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM)].
      Furthermore, we classified NGT into NGT-A (2-h blood glucose <120 mg/dl and 2-h
      glucosuria <50 mg/dl) and NGT-B (remaining NGT subjects). We then compared
      deltamyo-inositol (myo-inositol/creatinine ratio: 2-h after glucose load--before
      load) of each group to investigate the relationship between glucose intolerance
      and deltamyo-inositol. RESULTS: The glucose tolerance of NGT-B appeared to have
      deteriorated compared with NGT-A as determined by blood glucose, insulin, and
      glucosuria. There was very little effect of gender or age on deltamyo-inositol in
      NGT-A. deltamyo-inositol was significantly higher than that in NGT-A (0.5+/-7.1
      mg/g Cr) not only in IFG (8.7+/-19.5 mg/g Cr, P<0.0001), IGT (14.8+/-22.9 mg/g
      Cr, P<0.0001) and DM (79.5+/-37.1 mg/g Cr, P<0.0001), but in NGT-B (7.4+/-12.7
      mg/g Cr, P<0.0001). With 2 mg/g Cr as a tentative cut-off for deltamyo-inositol
      to detect NGT-A, sensitivity and specificity were 68% and 72%, respectively.
      CONCLUSIONS: The deltamyo-inositol can be use of a non-invasive and sensitive
      marker for glucose intolerance.

PMID- 15149888
TI  - Increased breath biomarkers of oxidative stress in diabetes mellitus.
AB  - BACKGROUND: Oxidative stress has been implicated in the major complications of
      diabetes mellitus, including retinopathy, nephropathy, neuropathy and accelerated
      coronary artery disease. There is a clinical need for a marker of oxidative
      stress which could potentially identify diabetic patients at increased risk for
      these complications. We measured oxidative age, a new breath marker of oxidative
      stress, in diabetic patients. METHODS: Three groups were studied: type 1 diabetes
      mellitus (n=9), type 2 diabetes mellitus (n=53) and non-diabetic normals (n=39).
      Volatile organic compounds (VOCs) in breath were assayed by gas chromatography
      and mass spectroscopy to construct the breath methylated alkane contour (BMAC), a
      three-dimensional display of oxidative stress markers, C4-C20 alkanes and
      monomethylated alkanes. The collective abundance of these VOCs was reduced to a
      single value, the oxidative age, comprising the volume under the curve of the
      BMAC corrected for chronological age. RESULTS: Oxidative age was significantly
      increased in type 1 diabetes (mean=0.103, S.E.M.=0.119, p<0.01) and type 2
      diabetes (mean=0.103, S.E.M.=0.047, p<0.05) compared to age-matched normals
      (mean=-0.248, S.E.M.=0.079). No significant correlation between oxidative age and
      blood glucose or hemoglobin A1C was observed in either group. CONCLUSIONS:
      Oxidative age, a marker of oxidative stress, was significantly increased in both
      type 1 and type 2 diabetes mellitus. Oxidative age merits further study as a
      candidate marker of risk for the complications of diabetes mellitus.

PMID- 15149889
TI  - Simvastatin reduces interleukin-1beta secretion by peripheral blood mononuclear
      cells in patients with essential hypertension.
AB  - BACKGROUND: Chronic low-grade inflammation may contribute to the increased risk
      of atherosclerosis in essential hypertension. Statins have been reported to have
      anti-inflammatory effects. We studied whether individuals with essential
      hypertension have increased interleukin-1beta (IL-1beta) secretion in peripheral
      blood mononuclear cells (PBMCs) and whether treatment with simvastatin lowered IL
      1beta secretion by PBMCs. METHODS: PBMCs were isolated by gradient centrifugation
      from 24 individuals with essential hypertension (EH) and 12 normotensive
      subjects. The IL-1beta concentrations in the supernatant from PBMCs were measured
      by enzyme-linked immunosorbent assay (ELISA). The patients with EH were then
      randomized to treatment with valsartan 80 mg/day or matching group who took the
      same drug valsartan 80 mg/day plus simvastatin 40 mg/day for 1 week. IL-1beta
      secretion by PBMCs was also measured. RESULTS: Compared with controls, patients
      with EH had increased IL-1beta [992+/-151 pg/ml, 912+/-102 pg/ml vs. 599+/-93
      pg/ml; P<0.05] secretion by PBMCs after stimulated by angiotensin II. Simvastatin
      treatment had a significant effect of decreasing IL-1beta [668+/-98 vs. 923+/-67
      pg/ml; P<0.05] secretion in PBMCs. The reductions were not correlated to changes
      in plasma lipids. CONCLUSIONS: This study shows that EH is associated with
      increased PBMCs activation and that treatment with simvastatin may partly
      attenuate this abnormality.

PMID- 15149890
TI  - Metabolic activity of dextromethorphan O-demethylation in healthy Japanese
      volunteers carrying duplicated CYP2D6 genes: duplicated allele of CYP2D6*10 does
      not increase CYP2D6 metabolic activity.
AB  - BACKGROUND: This study was designed to assess the metabolic activities of
      dextromethorphan O-demethylation in healthy Japanese subjects carrying duplicated
      CYP2D6 alleles, CYP2D6*1 x 2, CYP2D6*2 x 2 or CYP2D6*10 x 2. METHODS: Forty-one
      unrelated healthy Japanese subjects containing carriers who had previously been
      genotyped as CYP2D6*1 x 2/*2, CYP2D6*1/*2 x 2, and CYP2D6*10/*10 x 2 were
      phenotyped with dextromethorphan. RESULTS: The metabolic ratios of
      dextromethorphan/dextrorphan in subjects with CYP2D6*1 x 2/*2 or CYP2D6*1/*2 x 2
      were lower than those in subjects with CYP2D6*1/*2, while the metabolic ratios in
      subjects with CYP2D6*10/*10 x 2, as well as homozygotes for CYP2D6*10, were
      significantly (P<0.01) higher than those in homozygotes for CYP2D6*1.
      CONCLUSIONS: The results suggested that carriers with three functional CYP2D6
      genes, CYP2D6*1 x 2/*2 or CYP2D6*1/*2 x 2, are ultrarapid metabolizer phenotypes
      in Japanese. The results also suggested that there is no gene-dose effect with
      the dextromethorphan O-demethylation activities between carriers with two and
      three CYP2D6*10 mutated genes per genome. Therefore, CYP2D6*10 x 2 may play an
      important role for the treatment of Japanese patients as well as CYP2D6*10 which
      is mainly responsible for the intermediate metabolizers in Japanese.

PMID- 15149891
TI  - Simple and rapid detection of uncoupling protein-2 - 866G/A polymorphism by
      mutagenically separated polymerase chain reaction.
AB  - BACKGROUND: Uncoupling protein-2 (UCP2), a recently identified member of the
      mitochondrial transporter superfamily, is a candidate gene for obesity. A common
      G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose
      tissue mRNA expression in vivo. METHODS: We developed a rapid and simple method,
      mutagenically separated polymerase chain reaction (MS-PCR) for genotyping UCP2 -
      866G/A polymorphism. Two reverse mutagenic allele-specific primers of different
      lengths for the UCP2 - 866G/A polymorphic site were paired with the same forward
      primer in the same PCR reaction. RESULTS: Agarose gel electrophoresis (3.5%)
      showed at least one of the two allelic products and provided a within-assay
      quality control to exclude false-negative results. The 203-bp fragment of the PCR
      products was A allele-specific and the 183-bp fragment was G allele-specific. The
      frequencies of the UCP2 - 866G/A genotypes in 72 Japanese subjects were AA: 21
      (29.2%), AG: 32 (44.4%), and GG: 19 (26.4%). The results were confirmed by the
      PCR-RFLP genotyping method, in which a 360-bp fragment of PCR products was cut
      into 290- and 70-bp fragments by the restriction enzyme MluI when the G allele
      was present. This Japanese group showed a higher frequency of the AA genotype,
      which is associated with a low prevalence of obesity, than Caucasian populations.
      CONCLUSIONS: The MS-PCR technique is a simple, rapid, and reliable method for
      genotyping UCP2 - 866G/A polymorphism.

PMID- 15149892
TI  - N-acetyl-beta-D-glucosaminidase activity in urine of dental personnel.
AB  - BACKGROUND: Dental personnel is exposed to several potential nephrotoxic agents.
      Urinary N-acetyl-beta-d-glucosaminidase (U-NAG) activity has emerged as a
      sensitive marker of early nephrotoxicity. METHODS: U-NAG was evaluated, by
      fluorimetric assay, in urine from 30 healthy subjects and 30 dental personnels.
      RESULTS: The median value of U-NAG activity (133.5 U/mmol urinary creatinine (U
      Cr) in urines of dental personnel was not statistically different (P>0.05) from
      activity (100.7 U/mmol U-Cr) of control urines. CONCLUSIONS: The results suggest
      that, for dental personnel, exposure to potential nephrotoxic agents is not
      usually high enough to increase U-NAG activity.

PMID- 15149893
TI  - Handling of commercially available enzyme immunoassays for 8-iso-prostaglandin
      F2alpha (8-iso-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP) in clinical research and
      science: considerations from the analytical and review point of view.

PMID- 15149895
TI  - Hereditary spherocytosis in association with severe G6PD deficiency: report of an
      unusual case.

PMID- 15149896
TI  - One- and two-year prospective follow-up of cognitive behavior therapy or
      supportive psychotherapy.
AB  - We followed up over 90% of 57 motor vehicle accident survivors, who completed a
      controlled comparison of cognitive behavioral therapy (CBT) to supportive
      psychotherapy (SUPPORT). One-year results showed a continued significant
      advantage on categorical diagnosis (PTSD or not) and structured interview
      measures (CAPS) for CBT over SUPPORT. Other measures generally showed the same
      results. At two years, we were able to follow-up only 75% of one-year completers.
      Although there continued to be arithmetic differences favoring CBT over SUPPORT,
      with these attenuated samples only differences on PTSD Checklist and Impact of
      Event Scale scores and in overall categorical diagnoses were significant. There
      was very modest improvement from end of treatment to the two-year follow-up.

PMID- 15149897
TI  - Adjustment to chronic low back pain--the relative influence of fear-avoidance
      beliefs, catastrophizing, and appraisals of control.
AB  - The present study investigated the relative extent to which patients' adjustment
      to chronic low back pain (CLBP) was influenced by their fear-avoidance beliefs,
      their tendency to catastrophize, and their appraisals of control. Eighty-three
      CLBP patients completed a series of self-report measures before participating in
      a physical therapist-led intervention. Hierarchical multiple regression analyses
      revealed that patients' perceptions of their ability to decrease pain explained a
      small, but statistically significant, proportion of the variance in pain
      intensity. In addition, patients' levels of catastrophizing, as well as their
      fear-avoidance beliefs about both work and physical activity, were independently
      associated with levels of disability. Interestingly, however, when exploring the
      relative predictive utility of these three psychological factors, it became
      evident that fear-avoidance beliefs about physical activity (FABs-PA) were the
      only significant predictor of patients' disability. Specifically, those patients
      who exhibited higher levels of FABs-PA tended to report greater levels of
      disability, even after adjusting for age, sex and pain intensity.

PMID- 15149898
TI  - Trauma and autobiographical memory specificity in depressed inpatients.
AB  - Research on autobiographical memory has shown that clinical depression is
      associated with a difficulty in retrieving specific autobiographical memories in
      response to cue words. This study examined the relation between lack of
      autobiographical memory specificity and self-reported trauma in a group of
      depressed adults (N = 23). In addition to the Autobiographical Memory Test (AMT;
      Williams & Broadbent, 1986) participants completed a number of questionnaires
      assessing the presence of traumatic experiences in the past, level of depression
      and neuroticism. The number of specific responses was not related to depression
      severity, but was significantly associated with the presence and severity of
      reported physical abuse. Participants who had been victim of physical abuse were
      less specific than participants who had not been confronted with such physical
      adversities. The results are discussed in the context of a functional hypothesis
      about the developmental relations between memory specificity, trauma and
      depression.

PMID- 15149899
TI  - Predicting traumatic stress using emotional intelligence.
AB  - The study investigated whether emotional intelligence (EI) can predict how
      individuals respond to traumatic experiences. A random sample of 414 participants
      (181 male, 233 female) were administered a measure of EI along with the Impact of
      Event Scale--revised [IES-R; Weiss, D. S. & Marmar, C. R. (1997). The Impact of
      Events Scale--revised. In J.P. Wilson & T.M. Keane (Eds.), Assessing
      psychological trauma and PTSD (pp. 399-411). New York: Guilford Press], and the
      monitoring and blunting questionnaire [MBQ, Anxiety Stress Coping 7 (1994) 53].
      The results showed that participants with higher NEIS scores report fewer
      psychological symptoms relating to their traumatic experiences, that monitors are
      more likely to have higher NEIS scores than blunters. Traumatic events had a
      greater impact on females than males, and males had higher EI than females. The
      implications of these findings for using EI as a predictor for individuals who
      may experience traumatic stress are discussed.

PMID- 15149900
TI  - Assessment of eating disorder psychopathology in obese children and adolescents:
      interview versus self-report questionnaire.
AB  - The present study compared two methods for assessing binge eating and related
      eating disorder psychopathology in obese children and adolescents. A comparison
      was made between the child version of the Eating Disorder Examination (ChEDE) and
      the self-report version of the interview (ChEDE-Q). A total of 139 children and
      adolescents (aged 10-16 years) seeking inpatient treatment for obesity completed
      the ChEDE questionnaire and were administered the ChEDE interview afterwards. The
      ChEDE and ChEDE-Q were significantly correlated for the four subscales:
      restraint, eating concern, weight concern and shape concern. The ChEDE-Q
      generated consistently higher levels of eating disorder psychopathology. There
      was a significant discrepancy for the assessment of a more complex feature such
      as binge eating. Overall, the current study found lower levels of agreement
      between the EDE and EDE-Q than previously reported in adult samples. It appears
      that children and adolescents have difficulties in identifying binge-eating
      episodes when they receive no detailed instruction. It is concluded that a
      clinical interview is necessary to identify eating disorders in obese children
      and that a self-report questionnaire can only be used as a screening tool. Even
      then, thorough clarification of the definition of the eating disorder features is
      needed when using a self-report questionnaire.

PMID- 15149901
TI  - A parent-report measure of children's anxiety: psychometric properties and
      comparison with child-report in a clinic and normal sample.
AB  - This study examined the psychometric properties of the parent version of the
      Spence Children's Anxiety Scale (SCAS-P); 484 parents of anxiety disordered
      children and 261 parents in a normal control group participated in the study.
      Results of confirmatory factor analysis provided support for six intercorrelated
      factors, that corresponded with the child self-report as well as with the
      classification of anxiety disorders by DSM-IV (namely separation anxiety,
      generalized anxiety, social phobia, panic/agoraphobia, obsessive-compulsive
      disorder, and fear of physical injuries). A post-hoc model in which generalized
      anxiety functioned as the higher order factor for the other five factors
      described the data equally well. The reliability of the subscales was
      satisfactory to excellent. Evidence was found for both convergent and divergent
      validity: the measure correlated well with the parent report for internalizing
      symptoms, and lower with externalizing symptoms. Parent-child agreement ranged
      from 0.41 to 0.66 in the anxiety-disordered group, and from 0.23 to 0.60 in the
      control group. The measure differentiated significantly between anxiety
      disordered children versus controls, and also between the different anxiety
      disorders except GAD. The SCAS-P is recommended as a screening instrument for
      normal children and as a diagnostic instrument in clinical settings.

PMID- 15149902
TI  - Effects of suppressing neutral and obsession-like thoughts in normal subjects:
      beyond frequency.
AB  - Recent cognitive-behavioral theories on obsessive-compulsive disorder (OCD) show
      that deliberate attempts to suppress intrusive and undesirable thoughts lie at
      the genesis of clinical obsessions. In this paper the results of an experimental
      study on the suppression of neutral and obsession-like thoughts in normal
      subjects are presented. Eighty-seven university students performed in three
      experimental periods: (1) base-line monitoring, (2) experimental instruction, and
      (3) monitoring. For each of these periods, the frequency of the occurrence of a
      "white bear" thought or a personally relevant intrusive thought was registered.
      Half of the subjects received instructions to suppress the target-thought in
      period 2, and the other half were instructed to only monitor the target-thought
      in each of the experimental periods. Several measures were also obtained before
      and after the experiment: annoyance caused by the intrusion, suppression effort,
      subjective success, and evaluative appraisals of the target-thought. The results
      showed neither immediate nor delayed frequency increases of the target thought.
      However, evidence was found that deliberate thought suppression efforts,
      regardless of their content, had greater negative consequences than did non
      suppression. These results are discussed in relation to the recent cognitive
      proposals about OCD.

PMID- 15149903
TI  - Screening risks for intimate partner violence and primary care settings:
      implications for future abuse.
AB  - Most health care intervention models for intimate partner violence (IPV) are
      crisis driven and targeted to survivors of injury following episodes of physical
      violence. Knowledge about anticipatory and preventive approaches with women who
      are at risk for abuse is scarce, limiting professionals' ability to respond fully
      and effectively to this problem. This paper describes a retrospective, practice
      based research study of social work interventions in two hospital-based primary
      care practices. A total of 431 female patients completed a self-administered
      questionnaire developed for the early detection of IPV risk factors during
      routine health care visits. The study showed surprisingly high rates of multiple
      risk markers in an urban primary care population whose medical presentations
      ordinarily would not raise provider suspicion about abuse. Findings confirmed the
      willingness of primary care populations to freely partake in routine screening
      and support the value of early identification and intervention with populations
      at risk. Practice implications are discussed.

PMID- 15149904
TI  - Using chart reviews to assess postpartum substance abuse. A pilot study.
AB  - The use of chart reviews to assess substance use one-year postpartum was examined
      in this pilot study by comparing interviews with chart reviews for 23 women
      assessed positive for risk during pregnancy. There was no indication that
      providers asked about alcohol use in 83 percent of the charts, drug use in 57
      percent of the charts, and tobacco use in 26 percent of the charts. Few positive
      or negative matches between interviews and chart reviews were found because
      substance use was generally not noted. These findings underscore the need to
      interview women to obtain postpartum substance use information and suggest that
      providers may not adequately address this issue.

PMID- 15149906
TI  - Integrating the health and mental health needs of the chronically ill: a group
      for individuals with depression and sickle cell disease.
AB  - Concerns about high rates of depression among persons with sickle cell disease
      and no effective interventions for treatment of this condition were the impetuses
      for the study described in this paper. A groupwork service using cognitive
      behavioral and self-management techniques were integrated into health care
      services at a Comprehensive Sickle Cell Center to treat depression in a small
      group of patients. An interdisciplinary team that included health care and mental
      health providers from the Center and a social work researcher guided the
      endeavor. Principles of Intervention Research were applied in the development of
      the service and to evaluate its effectiveness. Among the findings were that study
      participants realized a decrease in depressive symptoms.

PMID- 15149905
TI  - Client satisfaction and empowerment through social work intervention.
AB  - This study examines the utility of satisfaction questionnaires in gauging the
      effectiveness of social work services in a paediatric hospital setting.
      Participants completed an empowerment scale before seeing a social worker.
      Approximately four weeks later, participants completed the empowerment scale
      again, at which time they also completed a satisfaction questionnaire. The
      difference between the pre- and post-test empowerment scores was compared with
      the satisfaction scores, and the influence of some demographic and intervention
      variables was examined. The results indicated that there was no significant
      relationship between participants' reported level of satisfaction with the social
      work service provided and the change in participants' empowerment scores before
      and after intervention. Most demographic and intervention variables tested did
      not yield any significant associations with satisfaction or change in
      empowerment. However, it was found that those who received both counselling and
      practical assistance (rather than only one or the other) and those with a higher
      level of education were more likely to report an increase in their level of
      empowerment after receiving social work intervention. This study lends further
      support to the contention that satisfaction questionnaires alone may not provide
      reliable information with regard to the utility and effectiveness of paediatric
      hospital social work intervention.

PMID- 15149907
TI  - Vision status among foster children in NYC: a research note.
AB  - A summary of the results of research on the vision status of foster children.
      Results indicate that the vision screenings being provided at mandated annual
      physical examinations are not sufficiently identifying children's vision
      dysfunctions.

PMID- 15149909
TI  - The case for integrating behavior change, client-centered practice and other
      evidence-based models into geriatric care management.
AB  - This paper describes the complexities of engaging a frail, elderly population in
      the process of behavior change to improve daily functioning. Implementation of a
      brief Purchase of Services (POS) benefit supplementing usual geriatric care
      management in an integrated, not-for-profit HMO environment is used to illustrate
      these complexities. Findings from the first two years of the four-year study of
      the intervention showed that one-third of the group of 541 study participants who
      were randomized as eligible to participate refused these free, enhanced services.
      The reasons for these refusals are examined, and a case is made for incorporating
      behavior change theory into traditional geriatric care management practice for
      cognitively intact clients in order to facilitate acceptance of needed services
      and increased patient autonomy.

PMID- 15149908
TI  - Elaborating a dichtomous measure of enrollment choice: HMOs vs FFS plans.
AB  - The objective of this study is to make health insurance plans more responsive to
      the needs of people by identifying plan characteristics that are important to
      consumers during their enrollment decisions. Employees from three companies were
      surveyed. Factor analysis indicated four dimensions of plans that are important
      to consumers: cost, freedom, quality, and psychosocial access. Among
      characteristics that described the "cost dimension" of plans, unpredictable out
      of-pocket costs was the most important. Among characteristics that described the
      "freedom" dimension of plans, freedom to go to any doctor without authorization
      from the primary care physician was most important.

PMID- 15149910
TI  - The coming of age for assisted living care: new options for senior housing and
      social work practice.
AB  - As the United States experiences substantial growth in its population that is 65
      years and older, development of safe housing and compassionate care for seniors
      is becoming a priority domestic issue. Assisted living is one of the fastest
      growing types of senior housing in the nation, attracting residents with a
      perceived combination of security, personal care services, less restrictive
      homelike environments and emphasis on independence, privacy and personal dignity.
      As there is limited reference to assisted living in the social work literature,
      this article selectively reviews the broader literature on the aging U.S.
      population and their need, assisted living as a senior housing and care option,
      the characteristics of this approach and the potential for social work practice
      in this evolving arena.

PMID- 15149911
TI  - Meeting the challenges of social work research in long term care.
AB  - As the number of long-term care (LTC) residents increases, issues related to
      quality of care and quality of life will continue to be of concern. Research in
      this area is clearly needed, yet it presents a variety of challenges related to
      the nature of the institutional setting and the compromised functional status of
      residents. The social work calling to give voice to those who are least heard and
      most needy demands that we rise to these challenges. Based on the authors'
      experiences in conducting research in LTC, three types of challenges are
      identified and discussed: institutional, participant, and research design.
      Recommendations for addressing these challenges are offered.

PMID- 15149912
TI  - Hospital social work: are we conducting the right type of research?
AB  - Given the current financial state of health care in the United States,
      intervention- or outcome-based research is essential for the survival of hospital
      social workers. The purpose of the current study was to systematically review the
      current literature on hospital social work to assess the effectiveness of
      hospital social work in implementing intervention- based research and to make
      recommendations for the future direction of research among hospital social
      workers. Over the 10-year period (1991-2001), a total of 44 peer-reviewed journal
      articles were identified for inclusion in the present study: 19 were qualitative
      articles and 25 were quantitative articles. Of these studies, only 5 studies were
      intervention based research. Possible strategies for increasing intervention
      research among hospital social workers were discussed.

PMID- 15149913
TI  - Creating a social work link to the burn community: a research team goes to burn
      camp.
AB  - Social work faculty and graduate students conducted focus groups with 52 burn
      injured adolescents from three burn camps to explore perceptions of their camp
      experience. Three themes emerged from data analysis that suggest burn camps play
      an important role in participants' lives. Camp is a place where burn-injured
      adolescents: (1) feel "normal" and accepted; (2) acquire insight in regard to
      self and meaning in life; and (3) gain confidence, increase self-esteem, and
      develop empathy. This project highlights how the use of qualitative research
      methods with grassroots organizations such as burn camps can serve as a link to
      greater social work involvement with this community.

PMID- 15149914
TI  - Deconstructing stigma: perceptions of HIV-seropositive mothers and their
      disclosure to children.
AB  - This study addressed the perceptions of stigma and disclosure behavior of HIV
      seropositive mothers. Eighty-eight HIV-seropositive women in New York City
      completed two independent measures of stigma, the Perceived Stigma Scale and the
      Devaluation-Discrimination Measure. Disclosers (67%) and nondisclosers (33%) were
      similar in most sociodemographic characteristics-marital status, race, religion
      and employment, with the exception of age and education. Significant differences
      were found between disclosure groups in the use of secrecy as a stigmamanagement
      tool and in perceived devaluation-discrimination associated with an HIV
      diagnosis. Nondisclosers to children were significantly more likely than
      disclosers to use secrecy as a stigma management tool (t =-2.76; p =.01), and to
      feel devalued and discriminated against as a result of HIV serostatus (t = 3.11;
      p =.01). Disclosure of parental HIV serostatus to children is an important aspect
      of continuous care and custody planning. Secrecy and perceptions of devaluation
      and discrimination related to HIV diagnosis should be seen as barriers to
      disclosure of serostatus to children.

PMID- 15149921
TI  - Older women who experience mistreatment:circumstances and outcomes.
AB  - Data from Virginia Adult Protective Services (APS) case files of 95 abused women
      aged 60 years and older were assessed to establish demographic trends; ability to
      care for self; type, pattern, and place of abuse; information on witnesses and
      alleged offenders; and case resolution and outcomes. The most common types of
      mistreatment reported were neglect, exploitation, and physical abuse. The women
      typically had several functional limitations and were dependent upon their family
      members for care. Most cases were not prosecuted, and the majority of women
      remain at risk for further abuse. Implications of these data for future research
      and practice are discussed.

PMID- 15149922
TI  - Tending and befriending: the intertwined relationships of quilters.
AB  - Using the convoy model of social relations, we explored the contributions of
      quilting activities to the relationships of middle- and older-aged women in three
      distinct groups: Amish, Appalachian, and Latter Day Saints. Semi-structured
      interviews were conducted with ten women from each group and analyzed
      qualitatively using McCracken's five-step method for analysis of long interviews.
      We found that these women had considerable horizontal and vertical connections to
      others. Specifically, they exhibited generativity by teaching their skills to
      others, building bonds with grandchildren through quilting, and leaving legacies
      through their quilts. Many developed friendships with other quilters that
      provided social support to deal with life challenges. Additional study of the
      contributions of mid-late life women's leisure activities to their social milieu,
      personal development, and well-being is needed.

PMID- 15149923
TI  - Body dissatisfaction in midlife women.
AB  - We examined the extent and correlates of body dissatisfaction among 1026 54-year
      old women from the MRC National Survey of Health and Development. Weight
      dissatisfaction was reported by nearly 80% of the sample and by over 50% of
      'normal weight' women (BMI < 25). Women indicated being most dissatisfied with
      their bodies currently, relative to their younger years, including their forties.
      Adjusting for BMI, dissatisfaction was highest in higher social class women and
      in those who rated themselves in poorer health. Women with poor body esteem,
      regardless of body size, were likely to avoid various everyday situations because
      of how they felt about their bodies. Adjusting for BMI, women who were happy with
      their weight were more likely to report distress about other aspects of their
      appearance. We suggest that body dissatisfaction in women of this age group
      merits further attention.

PMID- 15149924
TI  - Aging behind bars:health care for older female inmates.
AB  - As the numbers of women in prison have increased, so have the number of older
      women behind bars. These older women present unique problems for institutions
      trying to meet their health care needs. We report findings from our national
      pilot study of federal and state prisons for women. Prisons report basic services
      for physical and mental health care, and most report having hospice services.
      However, those that house larger percentages or that expect to house larger
      percentages of older prisoners do not significantly differ in their approaches to
      assessing and providing health care from their counterparts. By failing to
      anticipate the increase in older women, prisons may be failing to provide for
      many of the health needs of this vulnerable population.

PMID- 15149925
TI  - Exploring self-care among dementia caregivers:the role of perceived support in
      accomplishing exercise goals.
AB  - Support provided by family and friends may influence the extent to which older
      women who are primary caregivers for a spouse with dementia adhere to an exercise
      routine. The current study reports on qualitative interviews with 30 older female
      caregivers taking part in an exercise intervention regarding the support they
      received for their exercise goals. Results indicate that nearly all women
      received some level of verbal encouragement from family and friends, though far
      fewer had exercise partners or someone to stay with their husbands while they
      exercised. To reflect the wide variation observed in the amount of exercise
      support received and needed by caregivers, a typology of support situations was
      constructed as follows: Self-reliant, Well-supported, Under-supported, and
      Superfluous support. Implications for future exercise interventions targeting
      this population are discussed.

PMID- 15149926
TI  - Cognitive adaptation and women's adjustment to conjugal bereavement.
AB  - Conjugal bereavement is experienced by the majority of older women in enduring
      relationships. Although most experience considerable distress in the immediate
      aftermath of this loss, the majority adjusts over the course of time. The current
      study of self-selected participants applies the theory of cognitive adaptation in
      an attempt to distinguish between women who have successfully adjusted to the
      death of their husbands versus those who exhibit prolonged distress. Results of
      this study suggest that positivity biases in personally relevant information
      processing (i.e., self-deception, marital aggrandizement, dispositional optimism)
      are significantly associated with life satisfaction and the absence of
      psychiatric distress. The contribution of cognitive adaptation is maintained over
      and above that provided by personality variables (i.e., neuroticism,
      extraversion, openness to experience). Intervention strategies to treat enduring
      distress among widowed women are considered on the basis of these findings.

PMID- 15149927
TI  - Unclaimed treasures:older women's reflections on lifelong singlehood.
AB  - Ever-single, older women are a diverse group, whose experiences of singlehood
      have received little attention from researchers. In this qualitative study, eight
      women between the ages of 65 and 77 living in a mid-sized Southwestern Ontario
      city were interviewed about being ever single, including their perspectives of
      the benefits and drawbacks of this status at their current age. Data were
      collected in semi-structured interviews, and the constant comparative method was
      used for data analysis. Emergent themes illustrated how the women's stories of
      singlehood were affected by the sociopolitical contexts of their youth. Upon
      reflection, the women articulated the benefits of lifelong singlehood, strongly
      emphasizing their independence and "ability to be alone," which was viewed as
      very important as they aged. The drawbacks of singlehood focused on loneliness
      and the absence of a social support network, which took on particular importance
      as the women experienced increasing age and frailty. Overall, the participants
      expressed satisfaction with their marital status and defied common stereotypes
      about older, single women. Implications of these findings relate to the social
      structure of marital status and its impact upon the lives of women who remain
      single.

PMID- 15149928
TI  - Through gendered lens:explaining Chinese caregivers' task performance and care
      reward.
AB  - The Chinese cultural norm of xiao, or filial piety, has long been held
      responsible for the practice of familial caregiving for older parents. Yet few
      explore the gendered nature of such a cultural practice in the current changing
      economic dynamics. Using data collected in 1997-1999 from 110 Chinese caregivers
      who were caring for physically dependent elder parents, this researcher explores
      the influence of changing economic conditions and Chinese cultural values in
      caregiver task performance and reward. Findings suggest that Chinese caregiving
      is highly gendered: Women are more likely to be unemployed and provide more
      personal care than men; sons are not more likely than daughters to provide
      financial assistance for parents. Chinese cultural values are playing an
      important role sanctioning caregiver task performance. Caregivers who believed in
      patrilocal norms provided more financial assistance; caregivers who reported
      higher social pressure provided more personal care. While the caregivers' report
      of social pressure is positively related to the caregivers' performance in
      personal care tasks, it is negatively related to caregiver reward. The author
      further explores the gendered implications for the changing economy and culture
      in China.

PMID- 15149929
TI  - Meaning of housework and other unpaid responsibilities among older women.
AB  - This study explores the meaning and conditions of housework and other unpaid
      responsibilities for older women. Taped, in-person interviews were conducted with
      53 ethnically and economically diverse women, 55-84 years old. The interview
      guide contained open-ended questions regarding the process of taking on housework
      and other unpaid responsibilities and the centrality to personal identity.
      Participants reported shifts in perceptions of housework as work, decreased
      importance of housework with age, the attitude of care recipients affecting the
      experience and meaning of unpaid responsibilities, and the impact of historical
      racist events on viewing unpaid responsibilities as opportunity.

PMID- 15149930
TI  - Older women and the internet.
AB  - This study was designed to explore the effects that training had on older adults'
      willingness to use the Internet to manage their health care. The most interesting
      result was that out of 70 self-volunteers, 58 were women. Results show that
      highly educated women who either own a computer or have access to one, and have
      low levels of anxiety toward computers, with strong feelings of self-efficacy
      toward computers and the Internet, and an internal locus of control, are more
      willing than men to use the Internet to find medical information to manage a
      chronic health problem.

PMID- 15149931
TI  - Gender differences in identity processes and self-esteem in middle and later
      adulthood.
AB  - Gender differences were examined in the identity processes of identity
      assimilation (maintaining identity despite age changes), identity accommodation
      (changing identity) and balance (using both processes) and in the relationship of
      these processes to self-esteem. We tested a community sample of 222 adults (131
      females and 91 males) ranging from 40 to 84 years of age (M = 57.5, SD = 12.1).
      Analysis of variance yielded evidence showing greater use of identity
      accommodation for women. Identity accommodation was negatively associated with
      self-esteem for both genders, while identity assimilation was positively
      associated with self-esteem for women only. For both men and women, identity
      balance was positively related to self-esteem. Women's use of the identity
      processes in relation to self-esteem is discussed. Societal views on aging are
      suggested to impact women, such that they engage in identity accommodation while
      benefiting from identity assimilation. From these findings, it appears that
      examining the processes contributing to the maintenance of self-esteem may be a
      more useful approach to characterizing the aging process and gender differences
      than focusing on mean differences alone.

PMID- 15149933
TI  - Recovered memories:ethical guidelines to support professionals.
AB  - There is a need for guidelines on recovered memories to support the work of
      professionals and provide protection for clients. This paper highlights the value
      added by the Canadian Psychological Association's Guidelines for Psychologists
      Addressing Recovered Memories (Crozier and Pettifor, 1996) in assisting
      professionals to deal with ethical issues in this area. The Guidelines in
      combination with a rational and intuitive ethical decision-making process are
      applied to three vignettes involving sexual abuse and possible recovered
      memories. This paper offers professionals an opportunity to review their practice
      according to approved Guidelines for dealing with the difficult issue of
      recovered memories.

PMID- 15149934
TI  - Incest and women of color: a study of experiences and disclosure.
AB  - Clinical literature on incest trauma assumes a homogeneity of experience of all
      incest survivors including women of color. Experiences relating to community,
      culture, and family need to be acknowledged as salient aspects of the experiences
      of women of color who are also incest survivors. Twelve participants were
      interviewed regarding their experiences related to disclosure and coping.
      Participants described value systems, community mindedness, social attitudes,
      negative consequences amongst other social and cultural issues as factors
      affecting incest disclosure. Participants described cognitive reframing,
      determination and separation from the perpetrator as ways of coping with incest.

PMID- 15149935
TI  - Cultural and religious influences in maternal response to intrafamilial child
      sexual abuse:charting new territory for research and treatment.
AB  - The role of culture when providing services for families in the wake of child
      sexual abuse disclosure is a charged issue although surprisingly little attention
      has been given in the research literature to this. This article reports the
      findings of a grounded theory study exploring facets of maternal response, and
      aspects of more and less supportive responses, to children who were sexually
      abused by the mother's intimate partner. Ten mothers, chosen on the basis of
      theoretical sampling, provided information through in-depth interviews to
      understand how they responded emotionally and behaviourally to their child's
      disclosure. As well, three service providers were interviewed as key informants.
      The research revealed cultural and religious influences as affecting how mothers
      made meaning of the sexual abuse and the actions they took. Mothers from cultural
      backgrounds that adhere to rigid patriarchal norms identified themes of intense
      value conflicts regarding family preservation, loyalty binds between the
      perpetrating partner and child victim, and anxieties around being alienated from
      their extended family and ethnic community. They also reported that their
      cultural belief systems were not well understood by service providers. In
      parallel, helping professionals identified cultural issues as presenting barriers
      for engaging with some clients. Practice implications and research directions are
      discussed.

PMID- 15149936
TI  - Female and male undergraduates' attributions for sexual offending against
      children.
AB  - This study examined gender differences in undergraduates' attributions for child
      sex offending. One hundred and sixty-four undergraduates were asked to give the
      reasons why they think men sexually offend against children and to rate them
      using Benson's Attributional Scale across four dimensions: stability, locus,
      controllability and globality. A Grounded Theory methodology was applied to these
      reasons and a set of nine categories derived from the data. The results showed
      that undergraduates' reasons for child sexual abuse strongly parallel
      contemporary scientific theories of abuse, and that there were significant gender
      differences in the frequency with which participants cited various types of
      reasons given for sexual abuse. Females endorsed significantly more victim
      reasons than males, and also more power and control reasons than did males. In
      contrast, males endorsed significantly more sexual reasons for offending than did
      females. Furthermore, significant gender differences were found between the ways
      in which participants construed the reasons for sexual abuse, with females seeing
      the phenomenon as significantly more stable and internal than males. No
      significant gender differences were found on the dimensions of controllability
      and globality.

PMID- 15149937
TI  - Acute stress reactions to everyday stressful life events among sexual abuse
      survivors with PTSD.
AB  - This study examined symptoms of Acute Stress Disorder (ASD), which is often
      thought of as a precursor to PTSD, among 54 women who already had PTSD for
      childhood sexual abuse for which they were seeking treatment. We examined the
      prevalence of ASD symptoms as well as their relationships to trauma symptoms
      measured by the Trauma Symptom Checklist-40. The ASD diagnosis requires the
      occurrence of a traumatic life event as well as meeting specific symptoms
      criteria. We found that fourty-four percent of participants met all symptom
      criteria for ASD, but only three of these 24 participants described a traumatic
      life event. Moreover, ASD symptoms were significantly related to trauma symptom
      scores. These findings suggest that a significant proportion of women with PTSD
      for childhood sexual abuse may be highly symptomatic for everyday stressful
      events that would not be experienced as traumatizing to others. Thus, these
      individuals need assistance in coping with everyday life stressors that do not
      involve a serious threat or injury in addition to needing help to alleviate their
      trauma symptoms.

PMID- 15149938
TI  - Variation in nutritional risk among Mexican American and non-Mexican American
      homebound elders who receive home-delivered meals.
AB  - Good nutritional health is essential to prevent functional decline and improve
      quality of life. Little is known of disparities in the extent of risk for poor
      nutritional health among homebound Mexican American (MA) elders who receive Older
      American Act Nutrition Program (OAANP) home-delivered meals. In order to assist
      OAANP service providers in understanding racial/ethnic differences in nutritional
      risk, this study examined routinely collected data on 908 homebound MA and non-MA
      in the Texas Lower Rio Grande Valley. Homebound MA were more likely to report
      poverty, risk factors for and indicators of poor nutritional health. Independent
      of poverty and covariates,MA were more likely to report very high nutritional
      risk. This underscores the importance of understanding racial/ethnic disparities
      in the extent of risk for poor nutritional health for the development,
      implementation, and evaluation of effective strategies to alleviate nutritional
      health disparities.

PMID- 15149939
TI  - Applying the theory of planned behavior to fruit and vegetable consumption by
      older adults.
AB  - This study applied the Theory of Planned Behavior to fruit and vegetable intake
      among older adults. A cross-sectional questionnaire was administered to older
      adults (N = 205, mean age = 77 years) at senior centers. Most were women (74%),
      white (77%), and had >/= 12 years of education. Regression analyses showed that
      the theory constructs explained more than 40% and 18% (p < 0.0001) of the
      variance in intention and reported intake of fruits and vegetables, respectively.
      Perceived behavioral control was most important in explaining both intention and
      intake, followed by attitudes and subjective norms. Important control beliefs
      were related to convenience, preferences, time, and availability when eating out.
      These beliefs should be addressed in education for older adults to increase fruit
      and vegetable intake.

PMID- 15149940
TI  - Nutrition screening and assessment of anthropometry and bioelectrical impedance
      in the frail elderly: a clinical appraisal of methodology in a clinical setting.
AB  - Nutrition screening is recommended to identify those at risk for malnutrition;
      nutrition assessment by anthropometry and impedance is widely used to indicate
      nutritional status but may be problematical in the frail elderly in nursing
      homes. Acceptability, availability, suitability and appropriate reference data
      influence clinical application of these measurements. In our study, nutrition
      screening and assessment methodology were evaluated in 46 nursing home residents,
      mean age 86.3 +/- 6.6 years, mean weight 66.1 +/- 12.9 kg, mean height 163.1 +/-
      9.6 cm, and mean BMI 24.9 +/- 4.6 kg/m2. Significant correlations (P < 0.05) were
      found in all measures of body weight, BMI, body fatness and leanness.
      Interpretation of data by five different reference standards and cutoff points
      revealed wide variation in identification of malnutrition by anthropometry.
      Appropriate reference data for body lean and fatness are not yet available. Thus,
      population-specific methodology and reference standards are of crucial
      importance.

PMID- 15149942
TI  - Group nutrition education classes for older adults.
AB  - A thorough search of the literature revealed only nine articles published since
      1993 that focused on nutrition education for older adults attending group classes
      and that measured outcomes. A table summarizes the reports, including the
      theoretical bases, descriptions of interventions, participants and comparison
      groups, program outcomes, methods of verification, and follow-up after
      interventions. Only three of the studies explicitly indicated that elements of a
      stated behavioral change theory had been incorporated. All of the educators
      employed a variety of older adult educational strategies to enhance learning. Six
      research teams reported on classes where nearly half or more of the participants
      represented minority groups. Six studies included comparison groups. Types of
      outcomes included measurements of change in knowledge, attitudes/ beliefs,
      behaviors, and/or physiological measures, but the actual variables examined
      differed among reports. No consistent patterns were detected among reported
      outcomes. The longest follow-up after interventions ceased was seven months. The
      review addresses issues raised from an analysis of the quantity, quality and
      findings of the articles and makes suggestions for future research and offers
      preliminary ideas for developing group nutrition education classes for older
      adults. This is one of a series of reviews of recent literature on nutrition
      education for older adults.

PMID- 15149943
TI  - Barriers to nutrition education for older adults, and nutrition and aging
      training opportunities for educators, healthcare providers,volunteers and
      caregivers.
AB  - Literature citations of barriers to nutrition education found in those who teach
      and care for older adults, as well as within older adults themselves, are
      discussed. No attempt was made to compare educational barriers for learners of
      varying ages. These obstacles need to be addressed in order for nutrition to be
      taught or learned effectively so that nutrition practices and health improve.
      Barriers for healthcare professionals to providing nutrition education include
      misconceptions and stereotypes about older adults and about their nutritional
      concerns; lack of attention to and lack of funding for older adult educational
      programs; and difficulties recruiting older learners. Hindrances for older adults
      in responding to nutrition education can be categorized as attitudinal,
      motivational, environmental, and related to low literacy and poverty. Published
      examples of opportunities for education and training about nutrition and aging
      that are in place for health educators, healthcare providers, volunteers and
      caregivers regarding nutrition and aging are discussed. Suggestions are presented
      regarding future efforts to minimize educational barriers and to provide training
      for healthcare professionals, volunteers and caregivers. New research is needed
      in this field of study in order to realize the potential quality of life benefits
      and reduced healthcare costs associated with providing effective nutrition
      education to older adults. This is one of a series of reviews of recent
      literature on nutrition education for older adults.

PMID- 15149949
TI  - Insulin secretion in lipodystrophic HIV-infected patients is associated with high
      levels of nonglucose secretagogues and insulin resistance of beta-cells.
AB  - We examined whether plasma concentrations of nonglucose insulin secretagogues are
      associated with prehepatic insulin secretion rates (ISR) in nondiabetic, insulin
      resistant, human immunodeficiency virus (HIV)-infected, lipodystrophic patients
      (LIPO). Additionally, the negative feedback of insulin on ISR was evaluated. ISR
      were estimated by deconvolution of plasma C-peptide concentrations during fasting
      (basal) and during the last 30 min of a 120-min euglycemic insulin clamp (40
      mU.m(-2).min(-1)). Eighteen normoglycemic LIPO were compared with 25
      normoglycemic HIV-infected patients without lipodystrophy (controls). Thirty
      minutes before start of the clamp, a bolus of glucose was injected intravenously
      to stimulate endogenous insulin secretion. Insulin sensitivity index (SiRd) was
      estimated from glucose tracer analysis. LIPO displayed increased basal ISR (69%),
      clamp ISR (114%), basal insulin (130%), and clamp insulin (32%), all P < or =
      0.001, whereas SiRd was decreased (57%, P < 0.001). In LIPO, ISRbasal correlated
      significantly with basal insulin, alanine, and glucagon (all r > 0.65, P < 0.01),
      but not with glucose. In control subjects, ISR(basal) correlated significantly
      with insulin, glucagon, and glucose (all r > 0.41, P < 0.05), but not with
      alanine. In LIPO, ISRclamp correlated significantly with clamp free fatty acids
      (FFA), alanine, triglyceride, and glucagon (all r > 0.51, P < 0.05). In control
      subjects, ISRclamp correlated with clamp triglyceride (r = 0.45, P < 0.05).
      Paradoxically, in LIPO, ISRclamp correlated positively with clamp insulin (r =
      0.68, P < 0.01), which suggests an absent negative feedback of insulin on ISR.
      Our data support evidence that lipodystrophic, nondiabetic, HIV-infected patients
      exhibit increased ISR, which can be partially explained by an impaired negative
      feedback of insulin on beta-cells and an increased stimulation of ISR by FFA,
      alanine, triglyceride, and glucagon.

PMID- 15149950
TI  - Cytokine regulation of skeletal muscle fatty acid metabolism: effect of
      interleukin-6 and tumor necrosis factor-alpha.
AB  - IL-6 and TNF-alpha have been associated with insulin resistance and type 2
      diabetes. Furthermore, abnormalities in muscle fatty acid (FA) metabolism are
      strongly associated with the development of insulin resistance. However, few
      studies have directly examined the effects of either IL-6 or TNF-alpha on
      skeletal muscle FA metabolism. Here, we used a pulse-chase technique to determine
      the effect of IL-6 (50-5,000 pg/ml) and TNF-alpha (50-5,000 pg/ml) on FA
      metabolism in isolated rat soleus muscle. IL-6 (5,000 pg/ml) increased exogenous
      and endogenous FA oxidation by approximately 50% (P < 0.05) but had no effect on
      FA uptake or incorporation of FA into endogenous lipid pools. In contrast, TNF
      alpha had no effect on FA oxidation but increased FA incorporation into
      diacylglycerol (DAG) by 45% (P < 0.05). When both IL-6 (5,000 pg/ml) and insulin
      (10 mU/ml) were present, IL-6 attenuated insulin's suppressive effect on FA
      oxidation, increasing exogenous FA oxidation (+37%, P < 0.05). Furthermore, in
      the presence of insulin, IL-6 reduced the esterification of FA to triacylglycerol
      by 22% (P < 0.05). When added in combination with IL-6 or leptin (10 microg/ml),
      the TNF-alpha-induced increase in DAG synthesis was inhibited. In conclusion, the
      results demonstrate that IL-6 plays an important role in regulating fat
      metabolism in muscle, increasing rates of FA oxidation, and attenuating insulin's
      lipogenic effects. In contrast, TNF-alpha had no effect on FA oxidation but
      increased FA incorporation into DAG, which may be involved in the development of
      TNF-alpha-induced insulin resistance in skeletal muscle.

PMID- 15149951
TI  - Prior serum- and AICAR-induced AMPK activation in primary human myocytes does not
      lead to subsequent increase in insulin-stimulated glucose uptake.
AB  - Exposing isolated rat skeletal muscle to 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside [AICAR, a pharmacological activator of AMP-activated protein
      kinase (AMPK)] plus serum leads to a subsequent increase in insulin-stimulated
      glucose transport (Fisher JS, Gao J, Han DH, Holloszy JO, and Nolte LA. Am J
      Physiol Endocrinol Metab 282: E18-E23, 2002). Our goal was to determine whether
      preincubation of primary human skeletal muscle cells with human serum and AICAR
      (Serum+AICAR) would also induce a subsequent elevation in insulin-stimulated
      glucose uptake. Cells were preincubated for 1 h under 4 conditions: 1) without
      AICAR or serum (Control), 2) with serum, 3) with AICAR, or 4) with Serum+AICAR.
      Some cells were then collected for immunoblot analysis to assess phosphorylation
      of AMPK (pAMPK) and its substrate acetyl-CoA carboxylase (ACC). Other cells were
      incubated for an additional 4 h without AICAR or serum and then used to measure
      basal or insulin-stimulated 2-deoxyglucose (2-DG) uptake. Level of pAMPK was
      increased (P < 0.01) for myotubes exposed to Serum+AICAR vs. all other groups.
      Phosphorylated ACC (pACC) levels were higher for both Serum+AICAR (P < 0.05) and
      AICAR (P < 0.05) vs. Control and Serum groups. Basal (P < 0.05) and 1.2 nM
      insulin-stimulated (P < 0.005) 2-DG uptake was higher for Serum vs. all other
      preincubation conditions at equal insulin concentration. Regardless of insulin
      concentration (0, 1.2, or 18 nM), 2-DG was unaltered in cells preincubated with
      Serum+AICAR vs. Control cells. In contrast to results with isolated rat skeletal
      muscle, increasing the pAMPK and pACC in human myocytes via preincubation with
      Serum+AICAR was insufficient to lead to a subsequent enhancement in insulin
      stimulated glucose uptake.

PMID- 15149952
TI  - Glucosamine-induced alterations of mitochondrial function in pancreatic beta
      cells: possible role of protein glycosylation.
AB  - Chronic exposure of rat pancreatic islets and INS-1 insulinoma cells to
      glucosamine (GlcN) produced a reduction of glucose-induced (22.2 mM) insulin
      release that was associated with a reduction of ATP levels and ATP/ADP ratio
      compared with control groups. To further evaluate mitochondrial function and ATP
      metabolism, we then studied uncoupling protein-2 (UCP2), F1-F0-ATP-synthase, and
      mitochondrial membrane potential, a marker of F1-F0-ATP-synthase activity. UCP2
      protein levels were unchanged after chronic exposure to GlcN on both pancreatic
      islets and INS-1 beta-cells. Due to the high number of cells required to measure
      mitochondrial F1-F0-ATP-synthase protein levels and mitochondrial membrane
      potential, we used INS-1 cells, and we found that chronic culture with GlcN
      increased F1-F0-ATP-synthase protein levels but decreased glucose-stimulated
      changes of mitochondrial membrane potential. Moreover, F1-F0-ATP-synthase was
      highly glycosylated, as demonstrated by experiments with N-glycosidase F and
      glycoprotein staining. Tunicamycin (an inhibitor of protein N-glycosylation),
      when added with GlcN in the culture medium, was able to partially prevent all
      these negative effects on insulin secretion, adenine nucleotide content,
      mitochondrial membrane potential, and protein glycosylation. Thus we suggest that
      GlcN-induced pancreatic beta-cell toxicity might be mediated by reduced cell
      energy production. An excessive protein N-glycosylation of mitochondrial F1-F0
      ATP-synthase might lead to cell damage and secretory alterations in pancreatic
      beta-cells.

PMID- 15149953
TI  - Postexercise protein metabolism in older and younger men following moderate
      intensity aerobic exercise.
AB  - Regular aerobic exercise strongly influences muscle metabolism in elderly and
      young; however, the acute effects of aerobic exercise on protein metabolism are
      not fully understood. We investigated the effect of a single bout of moderate
      walking (45 min at approximately 40% of peak O2 consumption) on postexercise
      (POST-EX) muscle metabolism and synthesis of plasma proteins [albumin (ALB) and
      fibrinogen (FIB)] in untrained older (n = 6) and younger (n = 6) men. We measured
      muscle phenylalanine (Phe) kinetics before (REST) and POST-EX (10, 60, and 180
      min) using l-[ring-2H5]phenylalanine infusion, femoral arteriovenous blood
      samples, and muscle biopsies. All data are presented as the difference from REST
      (at 10, 60, and 180 min POST-EX). Mixed muscle fractional synthesis rate (FSR)
      increased significantly at 10 min POST-EX in both the younger (0.0363%/h) and
      older men (0.0830%/h), with the younger men staying elevated through 60 min POST
      EX (0.0253%/h). ALB FSR increased at 10 min POST-EX in the younger men only
      (2.30%/day), whereas FIB FSR was elevated in both groups through 180 min POST-EX
      (younger men = 4.149, older men = 4.107%/day). Muscle protein turnover was also
      increased, with increases in synthesis and breakdown in younger and older men.
      Phe rate of disappearance (synthesis) was increased in both groups at 10 min POST
      EX and remained elevated through 60 min POST-EX in the older men. A bout of
      moderate-intensity aerobic exercise induces short-term increases in muscle and
      plasma protein synthesis in both younger and older men. Aging per se does not
      diminish the protein metabolic capacity of the elderly to respond to acute
      aerobic exercise.

PMID- 15149954
TI  - Arginine synthesis is regulated by dietary arginine intake in the enterally fed
      neonatal piglet.
AB  - Arginine is conditionally indispensable in the neonate, and its synthesis in the
      intestine is not sufficient to meet requirements. It is not known how neonatal
      endogenous arginine synthesis is regulated and the degree to which proline and
      glutamate are used as precursors. Primed, constant intraportal and intragastric
      infusions of L-[U-14C]proline and L-[3,4-3H]glutamate, and intragastric L
      [guanido-14C]arginine were used to measure whole body and first-pass intestinal
      arginine synthesis in 10 neonatal piglets fed generous (1.80 g.kg(-1).day(-1)) or
      deficient (0.20 g.kg(-1).day(-1)) quantities of arginine for 5 days. Glutamate
      tracer was not detected in arginine, indicating a biologically insignificant
      conversion of <1% of arginine flux. Endogenous arginine synthesis from proline
      had obligatory (0.36 g.kg(-1).day(-1)) and maximal (0.68 g.kg(-1).day(-1)) levels
      (P < 0.05, pooled SE 0.05). Although first-pass gut metabolism is responsible for
      42-63% of whole body arginine synthesis, the gut is incapable of upregulating
      proline to arginine conversion during arginine deficiency, compared with a more
      than threefold increase without first-pass gut metabolism. These data suggest
      that upregulation of proline-to-arginine conversion occurs via increased arterial
      extraction of proline by the gut or in nonintestinal tissues. This study
      demonstrates that dietary arginine is an important regulator of endogenous
      arginine synthesis in the neonatal piglet and that proline, but not glutamate, is
      an important precursor for arginine synthesis in the neonate.

PMID- 15149955
TI  - Identification of iduronate-2-sulfatase in mouse pancreatic islets.
AB  - The lysosomal enzyme iduronate-2-sulfatase (IDS) is expressed in pancreatic
      islets and is responsible for degradation of proteoglycans, such as perlecan and
      dermatan sulfate. To determine the role of IDS in islets, expression and
      regulation of the gene and localization of the enzyme were investigated in mouse
      pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets
      and beta- and alpha-clonal cells, in which it was localized intracellularly in
      lysosomes. The transcriptional expression of Ids in mouse islets increased with
      glucose in a dose-dependent manner (11.5, 40.2, 88, and 179% at 5.5, 11.1, 16.7,
      and 24.4 mM, respectively, P < 0.01 for 16.7 and 24.4 mM glucose vs. 3 mM
      glucose). This increase was not produced by glyceraldehyde (1 mM) or 6
      deoxyglucose (21.4 mM) and was blocked by the addition of mannoheptulose (21.4
      mM). Neither insulin content nor secretory response to glucose (16.7 mM) was
      altered in mouse islets infected with lentiviral constructs carrying the IDS gene
      in sense orientation. Furthermore, no decrease in islet cell viability was
      observed in mouse islets carrying lentiviral contracts compared with controls.
      However, insulin content was reduced (35% vs. controls, P < 0.001) in islets
      infected with IDS antisense construct, while the secretory response of those
      islets to glucose was maintained. Inhibition of IDS by antisense infection led to
      an increase in lysosomal size and a high rate of insulin granule degradation via
      the crinophagic route in pancreatic beta-cells. We conclude that IDS is localized
      in lysosomes in pancreatic islet cells and expression is regulated by glucose.
      IDS has a potential role in the normal pathway of lysosomal degradation of
      secretory peptides and is likely to be essential to maintain pancreatic beta-cell
      function.

PMID- 15149956
TI  - Differential sensitivity of intranuclear and systemic oxytocin release to central
      noradrenergic receptor stimulation during mid- and late gestation in rats.
AB  - A number of changes occur in the oxytocin (OT) system during gestation, such as
      increases in hypothalamic OT mRNA, increased neural lobe and systemic OT, and
      morphological and electrophysiological changes in OT-containing magnocellular
      neurons, suggestive of altered neuronal sensitivity, which may be mediated by
      ovarian steroids. Because central norepinephrine (NE) and histamine (HA) are
      potent stimulators of OT release during parturition and lactation, the present
      study investigated the effects of central noradrenergic and histaminergic
      receptor activation on systemic (NE, HA) and intranuclear (NE) OT release in
      pregnant rats and in ovariectomized rats treated with ovarian steroids. Plasma OT
      levels in late gestation were significantly higher compared with all other
      groups, and neither adrenergic nor histaminergic receptor blockade decreased
      these elevated levels. Furthermore, the alpha-adrenergic agonist phenylephrine,
      but not histamine, stimulated systemic OT release to a significantly greater
      extent in late gestation than in midpregnant, ovariectomized, or steroid-treated
      females. Although basal extracellular OT levels in the paraventricular nucleus,
      as measured with microdialysis, were unchanged during pregnancy or steroid
      treatment, noradrenergic receptor stimulation of intranuclear OT release was
      significantly elevated in midgestation females compared with all other groups.
      These studies indicate that sensitivity of intranuclear and systemic OT release
      to noradrenergic receptor activation differentially varies during the course of
      gestation.

PMID- 15149958
TI  - Do recommended textbooks contain adequate information about bile salt
      transporters for medical students?
AB  - Several studies have recently highlighted a number of limitations in medical
      textbooks. The aims of this study were to 1) to assess whether available medical
      textbooks provided students with adequate information about bile salt
      transporters, 2) compare the level of detail and the amount of information
      provided in current textbooks on hepatic transport mechanisms with those
      available in the literature, and 3) compare the amount of information provided in
      medical textbooks on hepatocyte transport mechanisms with those involving other
      transporters e.g., those found in the nephron. Seventy medical textbooks from
      disciplines including physiology, pathology, cell biology, medicine, pediatrics,
      pharmacology, pathophysiology, and histology published during the past six years
      were examined. The literature on bile salt transport has been searched mainly
      from the Internet (MEDLINE and PubMed). Most textbooks failed to provide any
      information on transporters found in the basolateral and canalicular membranes of
      hepatocytes. There are also deficiencies in information on bile salt transporters
      in the terminal ileum. However, up to the end of 2002, 3,610 articles and reviews
      had been published on hepatobiliary and enterocyte transport of bile salts.
      During the same period (from 1965), 10,757 articles had been published on renal
      transport. Thus the contents of textbooks may reflect the overall volume of
      research knowledge on renal transport. However, despite our current understanding
      of hepatic and intestinal transport of bile salts and extensive research,
      particularly over the past 12 years, there are major deficiencies in textbooks in
      this area. These findings indicate that there is an imbalance in the contents of
      current textbooks and a lack of information about hepatobiliary physiology, bile
      salt transporters, bile formation, and mechanisms underlying cholestasis and drug
      induced injury. Authors, editors, and publishers of medical textbooks should
      consider the need to update the information provided on bile salt transporters.

PMID- 15149959
TI  - The polymerase chain reaction.
AB  - This essay on the polymerase chain reaction is one of a series developed as part
      of FASEB's efforts to educate the general public, and the legislators whom it
      elects, about the benefits of fundamental biomedical research-particularly how
      investment in such research leads to scientific progress, improved health, and
      economic well-being.

PMID- 15149960
TI  - Pedagogical effectiveness of innovative teaching methods initiated at the
      Department of Physiology, Government Medical College, Chandigarh.
AB  - Modern teaching trends in medical education exhibit a paradigm shift from the
      conventional classroom teaching methods adopted in the past to nonconventional
      teaching aids so as to encourage interactive forms of learning in medical
      students through active participation and integrative reasoning where the
      relationship of the teacher and the taught has undergone tremendous
      transformation. Some of the nonconventional teaching methods adopted at our
      department are learning through active participation by the students through
      computer-assisted learning (CD-ROMs), Web-based learning (undergraduate
      projects), virtual laboratories, seminars, audiovisual aids (video-based
      demonstrations), and "physioquiz."

PMID- 15149961
TI  - Evaluation of the teaching strategy of cardiovascular system in a problem-based
      curriculum: student perception.
AB  - It is generally acknowledged that an integrated approach to teaching
      cardiovascular system (CVS) is clinically relevant. However, very little
      attention has been paid with respect to student perception of teaching CVS in an
      integrated problem-based curriculum. A questionnaire on the feedback and
      perception of medical students (n = 60) to their learning experience of CVS
      exposed early in the problem-based integrated curriculum at the Arabian Gulf
      University (AGU) was used. The average percentage scores of positive student
      responses to items related to knowledge was 62.7%, to integration was 87.3%, and
      to skills was 77.1%. A significant positive correlation was observed among skills
      and knowledge (r = 0.408, P = 0.002), skills and integration (r = 0.506, P <
      0.000), and integration and knowledge (r = 0.294, P = 0.028). The lowest
      individual percentage score related to knowledge items was given to the role of
      resource sessions in understanding difficult concepts (32.7%). Interestingly,
      90.7% of the students were aware of the presence of gaps in their knowledge. On
      the other hand, 92.7% of students expressed their satisfaction with the study
      experience of CVS in the integrated problem-based approach. These results
      indicate that students overall achieved satisfactory learning outcome during the
      study of CVS in the problem-based integrated curriculum at AGU. The study also
      points out issues where improvement and fine tuning of the educational system can
      take place.

PMID- 15149962
TI  - Progesterone in milk: a simple experiment illustrating the estrous cycle and
      enzyme immunoassay.
AB  - Experiments designed for students in reproductive physiology are rare. Here, we
      describe a simple experiment concerning a physiological aspect of the
      reproductive system. Milk samples are obtained from cows in estrus, in midcycle,
      21 days after insemination, and in gestation. With these samples, the gestation
      or estrous stage is determined according to the progesterone level in milk that
      is measured using enzyme immunoassay. This experiment can therefore be used to
      demonstrate assay techniques and to illustrate the variations in progesterone
      concentrations during an estrous cycle and gestation. This exercise should be
      given after the reproduction section of the animal physiology course so that
      students can apply their knowledge concerning hormonal profiles during an estrous
      cycle.

PMID- 15149964
TI  - Expanding the traditional physiology class with asynchronous online discussions
      and collaborative projects.
AB  - Discussion and writing are very powerful ways to support learning. This article
      describes the use of a free, asynchronous online forum to expand student-teacher
      discussions beyond the time/place constraints of the physical physiology
      classroom. The main participants were medical students enrolled in physiology
      class at the University of Zagreb Medical School and their teachers. The
      assessment data were collected by the electronic administration of the software,
      by anonymous paper questionnaires, and by the results of the final examination in
      physiology. During one academic year, 25% (n = 55) of 220 students enrolled in a
      traditional physiology course participated in online discussions. Physiology
      teachers and other faculty also joined the forum. All forum members (n = 99)
      posted 395 messages. Nine documents were published by six students who
      participated in two online collaborative projects. The difference in the mean
      grade of the final examination in physiology between student members and
      nonmembers was statistically significant (P = 0.0328, t = 2.1526). Students who
      participated in Web discussions were self-selected. Likely, they are the most
      motivated students, who would perform better on the final examination with or
      without this resource. Nevertheless, using an online forum could be very
      successful in teaching critical thinking in physiology because the Internet
      removes traditional time/place barriers. However, new barriers related to
      technology and behavioral changes are created. For most teachers and students,
      the main obstacles to information technology implementation are lack of
      motivation and lack of professional incentives. To overcome these barriers,
      institutional support is needed for both students and teachers.

PMID- 15149963
TI  - Two models for an effective undergraduate research experience in physiology and
      other natural sciences.
AB  - 68A realistic research experience is beneficial to undergraduate students, but it
      is often difficult for liberal arts colleges to offer this opportunity. We
      describe two approaches for developing and maintaining an interdisciplinary
      research program at small colleges. An active and continuing involvement of an
      individual with extensive research experience is an essential element in both.
      One model was developed by the faculty of Taylor University, Upland, IN and a
      research scientist who had retired from a major university to join the Taylor
      faculty as their first Research Professor. The school's Science Research Training
      Program was initially funded by a modest endowment provided by interested alumni
      and by extramural grants awarded to the Research Professor and to the
      institution; the program now enjoys significant funding from diverse sources.
      Taylor is not located near any large research university and consequently
      supplies all resources required for the experiments and stipends for students
      pursuing projects full-time during the summer. The second model was developed by
      the faculty at Asbury College in Wilmore, KY, working with a scientist having a
      full-time appointment at the University of Kentucky and a part-time appointment
      at the college. In this approach, Asbury faculty may place their students for a
      period of training, often during the summer, in a laboratory of a cooperating
      host faculty at the University of Kentucky or other institution. The host faculty
      funds the research and pays a stipend to those students who work full-time during
      the summer. Relationships established between faculty at the College and at the
      University of Kentucky have been mutually beneficial. The success of both
      programs is evidenced by the students' presenting their data at state and
      national scientific meetings, by their publishing their results in national
      journals, and by the undergraduate school faculty developing independent research
      programs.

PMID- 15149965
TI  - Postsynaptic potential summation and action potential initiation: function
      following form.

PMID- 15149966
TI  - Myelinated vs. unmyelinated nerve conduction: a novel way of understanding the
      mechanisms.

PMID- 15149967
TI  - Restoring physiology to the undergraduate biology curriculum: a call to action.

PMID- 15149968
TI  - Restoring physiology to the undergraduate biology curriculum: a call to action.

PMID- 15149969
TI  - Cisplatin-induced cell death is EGFR/src/ERK signaling dependent in mouse
      proximal tubule cells.
AB  - Cisplatin treatment induces extensive death of the proximal tubules in mice. We
      also demonstrated that treatment of immortalized mouse proximal tubule cells
      (TKPTS) with 25 microM cisplatin induces apoptotic death in vitro. Here, we
      demonstrate that members of the MAPKs such as ERK, JNK, and p38 are all activated
      after cisplatin treatment both in vivo and in vitro. Because MAPKs mediate cell
      survival and death, we studied their role in cisplatin-induced cell death in
      vitro. Apoptosis was confirmed by cell morphology, fluorescence-activated cell
      sorting analysis, annexin V/propidium iodide binding, and caspase-3 activation in
      TKPTS cells. Inhibition of ERK, but not JNK or p38, abolished caspase-3
      activation and apoptotic death, suggesting a prodeath role of ERK in cisplatin
      induced injury. We also determined that cisplatin-induced ERK as well as caspase
      3 activation are epidermal growth factor receptor (EGFR) and c-src dependent
      because inhibition of these genes inhibited ERK and caspase-3 activation and
      attenuated apoptotic death. These results suggest that caspase-3 mediates
      cisplatin-induced cell death in TKPTS cells via an EGFR/src/ERK-dependent
      pathway. We also suggest that the prodeath effect of ERK is injury type dependent
      because during oxidant injury, ERK supports survival rather than death in the
      same cells. We propose that injury-specific outcome diverges downstream from ERK
      in cisplatin- or H(2)O(2)-mediated cell survival and death.

PMID- 15149970
TI  - Ion and diuretic specificity of chimeric proteins between apical Na(+)-K(+)-2Cl(
      ) and Na(+)-Cl(-) cotransporters.
AB  - The mammalian kidney bumetanide-sensitive Na(+)-K(+)-2Cl(-) and thiazide
      sensitive Na(+)-Cl(-) cotransporters are the major pathways for salt reabsorption
      in the thick ascending limb of Henle's loop and distal convoluted tubule,
      respectively. These cotransporters serve as receptors for the loop- and thiazide
      type diuretics, and inactivating mutations of corresponding genes are associated
      with development of Bartter's syndrome type I and Gitleman's disease,
      respectively. Structural requirements for ion translocation and diuretic binding
      specificity are unknown. As an initial approach for analyzing structural
      determinants conferring ion or diuretic preferences in these cotransporters, we
      exploited functional differences and structural similarities between Na(+)-K(+)
      2Cl(-) and Na(+)-Cl(-) cotransporters to design and study chimeric proteins in
      which the NH(2)-terminal and/or COOH-terminal domains were switched between each
      other. Thus six chimeric proteins were produced. Using the heterologous
      expression system of Xenopus laevis oocytes, we observed that four chimeras
      exhibited functional activity. Our results revealed that, in the Na(+)-K(+)-2Cl(
      ) cotransporter, ion translocation and diuretic binding specificity are
      determined by the central hydrophobic domain. Thus NH(2)-terminal and COOH
      terminal domains do not play a role in defining these properties. A similar
      conclusion can be suggested for the Na(+)-Cl(-) cotransporter.

PMID- 15149972
TI  - Estrogen receptor alpha-mediated events promote sex-specific diabetic glomerular
      hypertrophy.
AB  - Sex differences in the incidence and progression of renal diseases suggest a
      protective role for estrogen. This study examined the role of estrogen receptor
      alpha (ERalpha)-mediated events in normal and diabetic renal and glomerular
      growth. Wild-type and ERalpha-null mice (ERKO) were observed over 2 wk of
      streptozocin-induced diabetes. Blood glucose was monitored, and insulin was given
      daily to maintain levels of 250-350 mg/dl. Body weight, kidney weight, glucose,
      insulin, renal transforming growth factor-beta(1), and glomerular area were
      examined for effects of sex, genotype, and diabetes. Genotype had no effect on
      glomerular or renal size in male mice regardless of metabolic state. Nondiabetic
      female ERKO mice had kidney weights approaching those of wild-type males and much
      greater than those of wild-type females (0.15 +/- 0.04 vs. 0.11 +/- 0.04 g; P <
      0.001). When only diabetic mice were studied, sex and/or genotype showed no
      effect on renal weight. Diabetic female ERKO mice had smaller glomerular areas
      than wild types (2,799 +/- 159 vs. 3,409 +/- 187 microm(2); P = 0.01). Glomerular
      areas were similar in diabetic wild-type and ERKO males (3,020 +/- 199 vs. 3,406
      +/- 176 microm(2)). Transforming growth factor-beta(1) levels, expressed as
      picograms per milligram total protein, were similar in diabetic wild-type and
      ERKO males (1.0 +/- 0.6 vs. 0.9 +/- 0.6). In diabetic females, wild types had
      significantly higher levels of this growth factor than ERKO mice (3.8 +/- 0.7 vs.
      1.1 +/- 0.6; P = 0.005). ERalpha-mediated processes influence normal and diabetic
      renal and glomerular size, but only in female mice. These data do not support a
      protective role for ERalpha-mediated events in diabetic nephropathy.

PMID- 15149971
TI  - Basolateral ammonium transport by the mouse inner medullary collecting duct cell
      (mIMCD-3).
AB  - The renal collecting duct is the primary site for the ammonia secretion necessary
      for acid-base homeostasis. Recent studies have identified the presence of
      putative ammonia transporters in the collecting duct, but whether the collecting
      duct has transporter-mediated ammonia transport is unknown. The purpose of this
      study was to examine basolateral ammonia transport in the mouse collecting duct
      cell (mIMCD-3). To examine mIMCD-3 basolateral ammonia transport, we used cells
      grown to confluence on permeable support membranes and quantified basolateral
      uptake of the radiolabeled ammonia analog [14C]methylammonia ([14C]MA). mIMCD-3
      cell basolateral MA transport exhibited both diffusive and transporter-mediated
      components. Transporter-mediated uptake exhibited a Km for MA of 4.6 +/- 0.2 mM,
      exceeded diffusive uptake at MA concentrations below 7.0 +/- 1.8 mM, and was
      competitively inhibited by ammonia with a Ki of 2.1 +/- 0.6 mM. Transporter
      mediated uptake was not altered by inhibitors of Na+-K+-ATPase, Na+-K+-2Cl(-)
      cotransporter, K+ channels or KCC proteins, by excess potassium, by extracellular
      sodium or potassium removal or by varying membrane potential, suggesting the
      presence of a novel, electroneutral ammonia-MA transport mechanism. Increasing
      the outwardly directed transmembrane H+ gradient increased transport activity by
      increasing Vmax. Finally, mIMCD-3 cells express mRNA and protein for the putative
      ammonia transporter Rh B-glycoprotein (RhBG), and they exhibit basolateral RhBG
      immunoreactivity. We conclude that mIMCD-3 cells express a basolateral
      electroneutral NH4+/H+ exchange activity that may be mediated by RhBG.

PMID- 15149974
TI  - The European Congress of Radiology 2004.

PMID- 15149973
TI  - Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in
      epithelial cells.
AB  - Aquaporin-4 (AQP4) water channels exist as heterotetramers of M1 and M23 splice
      variants and appear to be present in orthogonal arrays of intramembraneous
      particles (OAPs) visualized by freeze-fracture microscopy. We report that AQP4
      forms OAPs in rat gastric parietal cells but not in parietal cells from the mouse
      or kangaroo rat. Furthermore, the organization of principal cell OAPs in
      Brattleboro rat kidney is perturbed by vasopressin (arginine vasopressin).
      Membranes of LLC-PK(1) cells expressing M23-AQP4 showed large, abundant OAPs, but
      none were detectable in cells expressing M1-AQP4. Measurements of osmotic
      swelling of transfected LLC-PK(1) cells using videomicroscopy, gave osmotic water
      permeability coefficient (P(f)) values (in cm/s) of 0.018 (M1-AQP4), 0.019 (M23
      AQP4), and 0.003 (control). Quantitative immunoblot and immunofluorescence showed
      an eightfold greater expression of M1- over M23-AQP4 in the cell lines,
      suggesting that single-channel p(f) (cm(3)/s) is much greater for the M23
      variant. Somatic fusion of M1- and M23-AQP4 cells (P(f) = 0.028 cm/s) yielded
      OAPs that were fewer and smaller than in M23 cells alone, and M1-to-M23
      expression ratios ( approximately 1:4) normalized to AQP4 in M1 or M23 cells
      indicated a reduced single-channel p(f) for the M23 variant. Expression of an M23
      AQP4-Ser(111E) mutant produced approximately 1.5-fold greater single-channel p(f)
      and OAPs that were up to 2.5-fold larger than wild-type M23-AQP4 OAPs, suggesting
      that a putative PKA phosphorylation site Ser(111) is involved in OAP formation.
      We conclude that the higher-order organization of AQP4 in OAPs increases single
      channel osmotic water permeability by one order of magnitude and that
      differential cellular expression levels of the two isoforms could regulate this
      organization.

PMID- 15149975
TI  - Acetabular fractures revisited: part 1, redefinition of the Letournel anterior
      column.
AB  - OBJECTIVE: The objective of part 1 of this study is to redefine the Letournel
      anterior column on the basis of developmental and adult pelvic skeletal anatomy.
      MATERIALS AND METHODS: The axial CT scans of 112 randomly selected patients with
      acetabular fracture or fracture-dislocations admitted to a level I trauma center
      between January 1998 and December 2000 were analyzed by an experienced orthopedic
      trauma surgeon and two experienced emergency radiologists. When available, 3D
      reformatted images were analyzed as well. The discrepancy between the Letournel
      definition of the anterior and posterior columns became readily apparent.
      Standard text books of anatomy and surgical anatomy were referenced relative to
      the embryologic and adult components of the acetabulum. RESULTS: The anterior
      column is redefined with its superior border being the anatomic arcuate and
      iliopectineal lines, thereby coinciding with the superior border (arcuate line)
      of the Letournel posterior column. CONCLUSION: Redefinition of the anterior
      column eliminates diagnostic ambiguity of the Letournel elementary anterior
      column fracture as well as the Letournel associated anterior column or wall with
      hemitransverse fracture. The redefined anterior column is integral to the CT
      based classification described in part 2 of our study.

PMID- 15149976
TI  - Acetabular fractures revisited: part 2, a new CT-based classification.
AB  - OBJECTIVE: The objective of this investigation was to provide a new CT-based
      classification of acetabular fractures. MATERIALS AND METHODS: The axial CT scans
      of 112 randomly selected acetabular fractures in patients admitted to a level 1
      trauma center between January 1998 and December 2000 were analyzed by an
      experienced orthopedic trauma surgeon and two experienced emergency radiologists.
      When available, 3D reformatted images were analyzed as well. The fracture pattern
      for each acetabular fracture, with respect to column walls and extension beyond
      the acetabulum, when present, was recorded. Fracture comminution was not a
      defining characteristic. RESULTS: Analysis of the 112 acetabular fracture
      patterns showed that each fracture fell into one of four broad categories.
      Category 0 included wall fractures only. Category I included acetabular fractures
      limited to a single (anterior or posterior) column. Category II fractures
      included those involving both the anterior and posterior columns; category II
      fractures were further subdivided into those with no fracture extension beyond
      the acetabulum, those with superior or inferior extension, and those with both
      superior and inferior extensions beyond the acetabulum. Category III fractures
      included only the "floating" acetabulum, which is defined as an acetabular
      fracture in which the acetabulum is separated from the axial skeleton both
      anteriorly and posteriorly. CONCLUSION: The axial CT display of acetabular
      fracture patterns provides a basis for a classification of acetabular fractures
      that is simple, unambiguous, readily understood by both radiologists and
      orthopedic surgeons and provides clear direction for both diagnosis and surgical
      treatment planning. Category and subcategory fracture specificity creates a
      mechanism for intra- and interdepartmental postoperative assessment of any of the
      individual acetabular fracture types.

PMID- 15149977
TI  - Role of a quantitative D-dimer assay in determining the need for CT angiography
      of acute pulmonary embolism.
AB  - OBJECTIVE: Our goal was to use the results of a quantitative D-dimer assay to
      determine the need for pulmonary CT angiography in patients suspected of having
      acute pulmonary embolism. MATERIALS AND METHODS: From July 2001 to December 2002,
      755 patients underwent pulmonary CT angiography for the evaluation of acute
      pulmonary embolism. A rapid, fully automated quantitative D-dimer assay was
      obtained in more than half the patients. The electronic medical records of the
      patients were subsequently reviewed to analyze the negative predictive value of
      the D-dimer assay in the diagnostic workup of acute pulmonary embolism and to
      determine the outcome of the patients who had negative findings on both D-dimer
      assay and pulmonary CT angiography at 3-month follow-up. RESULTS: Of the 755
      patients who underwent pulmonary CT angiography, 666 (88.2%) had negative
      findings, 73 (9.7%) had positive findings, and 16 (2.1%) were indeterminate. A
      total of 426 patients underwent both pulmonary CT angiography and D-dimer level
      evaluation, and 84 of these had negative findings (< 0.4 microg/mL) on D-dimer
      assay. Eighty-two of the 84 patients with negative findings on D-dimer assay had
      negative findings on pulmonary CT angiography; two were indeterminate and both
      subsequently had low-probability ventilation-perfusion studies. Among patients
      with positive D-dimer assays, no one with a level between 0.4 and 1.0 microg/mL
      had pulmonary CT angiography with findings positive for pulmonary embolism.
      CONCLUSION: A quantitative D-dimer assay was effective in excluding the need for
      pulmonary CT angiography and had high negative predictive value when the D-dimer
      level was less than 1.0 microg/mL.

PMID- 15149978
TI  - Quadriceps fat pad signal intensity and enlargement on MRI: prevalence and
      associated findings.
AB  - OBJECTIVE: The purpose of this investigation was to characterize the MRI
      appearance of the quadriceps fat pad and to correlate the findings with other
      knee abnormalities, anatomic measurements of the extensor mechanism, and findings
      from history and at physical examination. MATERIALS AND METHODS: Ninety-two
      consecutive knee MRI examinations from 84 patients were retrospectively reviewed
      by two musculoskeletal radiologists for quadriceps fat pad enlargement and signal
      intensity. Other data from the retrospective review included infrapatellar and
      prefemoral fat pad signal intensity, quadriceps and patellar tendon
      abnormalities, joint effusion, medial plica, chondromalacia, articular muscle
      thickness, and prepatellar edema. The patellar length, patellar articular length,
      patellar tendon length, and femoral sulcus angle were measured. MRI reports were
      reviewed for meniscal and ligament abnormalities. Clinical data were reviewed for
      findings of anterior knee pain in the history and at physical examination. The
      chi-square and Student's t tests were used to determine significant associations.
      RESULTS: Twelve percent (11/92) of MRI examinations showed quadriceps fat pad
      mass effect on the suprapatellar recess, which was associated with intermediate
      or fluid signal intensity of the quadriceps fat pad (chi(2) = 7.19, p = 0.0274)
      but with no other findings on knee MRI. Anterior knee pain at physical
      examination was associated with quadriceps fat pad mass effect (chi(2) = 8.76, p
      = 0.0031), medial collateral ligament abnormality (chi(2) = 4.83, p = 0.0031),
      and history of anterior knee pain (chi (2) = 22.76, p < 0.0001). CONCLUSION:
      Enlargement of the quadriceps fat pad on MRI has a prevalence of 12% and is
      significantly associated with intermediate or fluid signal intensity of the
      quadriceps fat pad and anterior knee pain.

PMID- 15149980
TI  - Imaging findings of fibrous dysplasia with histopathologic and intraoperative
      correlation.

PMID- 15149981
TI  - Computer-assisted quantitative analysis of bone marrow edema of the knee: initial
      experience with a new method.
AB  - OBJECTIVE: The purpose of this study was to describe a largely observer
      independent computer-assisted method for accurate quantitative analysis of bone
      marrow edema. MATERIALS AND METHODS: Ten patients with bone marrow edema of the
      knee were included in the study. Coronal STIR images of the affected knees were
      obtained using a 1.0-T MR scanner. Size and signal intensity of the bone marrow
      edema were assessed on the basis of gray-scale value analysis and calculation of
      a threshold value for differentiating normal and edematous bone marrow. All
      measurements were carried out three times for statistical analysis. RESULTS: The
      intraobserver coefficient of variation was 0.89% for the volume and 0.94% for the
      signal intensity of the bone marrow edema, showing the small impact of manual
      interference on results produced with this method. CONCLUSION: A computer
      assisted method for quantification of bone marrow edema has been described.
      Intraobserver variation was very low, indicating excellent reproducibility of
      results. Although the method is too time-consuming for clinical use, it is
      recommended for research purposes.

PMID- 15149983
TI  - Discrimination of tuberculous spondylitis from pyogenic spondylitis on MRI.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of MRI for
      discrimination between tuberculous spondylitis and pyogenic spondylitis.
      MATERIALS AND METHODS: MR images of 52 patients who had MRI of the spine and
      confirmed spondylitis were retrospectively reviewed. After review of medical
      records, we compared MRI findings in 20 patients with tuberculous spondylitis and
      20 patients with pyogenic spondylitis. Statistical analysis was performed with
      the chi-square test. RESULTS: The reviewer identified tuberculous spondylitis
      with sensitivity, specificity, and accuracy of 100% (20/20), 80% (16/20), and 90%
      (36/40), and pyogenic spondylitis with sensitivity, specificity, and accuracy of
      80% (16/20), 100% (20/20), and 90% (36/40), respectively. The patients with
      tuberculous spondylitis had a significantly higher incidence of MRI findings as
      follows (p < 0.05): a well-defined paraspinal abnormal signal (95% [19/20] in
      tuberculous vs 25% [5/20] in pyogenic), a thin and smooth abscess wall (95%
      [19/20] vs 15% [3/20]), combination of both findings (90% [18/20] vs 0% [0/20]),
      presence of paraspinal or intraosseous abscess (95% [19/20] vs 50% [10/20]),
      subligamentous spread to three or more vertebral levels (85% [17/20] vs 40%
      [8/20]), involvement of multiple vertebral bodies (60% [12/20] vs 25% [5/20]),
      thoracic spine involvement (40% [8/20] vs 10% [2/20]), and hyperintense signal on
      T2-weighted images (95% [19/20] vs 65% [13/20]). CONCLUSION: MRI was accurate for
      differentiation of tuberculous spondylitis from pyogenic spondylitis.

PMID- 15149984
TI  - Usefulness of simultaneous acquisition of spatial harmonics technique for MRI of
      the knee.
AB  - OBJECTIVE: Simultaneous acquisition of spatial harmonics (SMASH) is a parallel
      imaging technique that uses fewer echoes than conventional techniques to obtain
      the desired resolution. Images are produced in a shorter time period using the
      SMASH technique than conventional techniques. This study assesses the usefulness
      of the SMASH technique in the MRI evaluation of the knee. SUBJECTS AND METHODS.
      Three experienced musculoskeletal radiologists prospectively interpreted MR
      images of the knee in 50 consecutive patients. All patients underwent a complete
      MRI examination of the knee on a 1.5-T MRI scanner. Sagittal proton density fat
      saturated and coronal T1-weighted images were obtained. In addition, fat
      saturated T2-weighted images were obtained in the coronal, sagittal, and axial
      planes. SMASH T2-weighted imaging in the coronal, axial and sagittal planes took
      6 min 38 sec, whereas fast spin-echo conventional T2-weighted imaging took 11 min
      45 sec to obtain images in the same planes. Each radiologist interpreted the knee
      MR examinations prospectively and was unaware whether the images had been
      obtained using the SMASH T2-weighted or fat-saturated T2-weighted technique. The
      radiologists provided a report. The three radiologists independently performed a
      retrospective review of both the fat-saturated T2-weighted and SMASH T2-weighted
      images. The radiologists were blinded as to which sequence was fat-saturated T2
      weighted and which was SMASH T2-weighted. They were asked to reinterpret the
      images and determine whether either of the T2-weighted sequences altered the
      original interpretation. RESULTS: There was no intraobserver variability in MRI
      interpretations with the use of SMASH imaging as compared with fat-saturated T2
      weighted images. Thirty-four patients underwent arthroscopy after imaging.
      Findings at arthroscopy in those patients were as follows: 28 meniscal tears, 12
      anterior cruciate ligament tears, and nine chondral defects. In some patients,
      multiple abnormalities were detected on MRI. All arthroscopy findings correlated
      with prospective MRI interpretations. CONCLUSION: The use of SMASH T2-weighted
      imaging as opposed to fat-saturated T2-weighted imaging results in a significant
      decrease in imaging time (> 5-min decrease for each knee examination) without
      affecting the MRI interpretation or patient clinical outcome.

PMID- 15149985
TI  - Complications after percutaneous transaxillary implantation of a catheter for
      intraarterial chemotherapy of liver tumors: clinical relevance and management in
      204 patients.
AB  - OBJECTIVE: The purposes of the study were to evaluate the complications of
      patients who underwent percutaneous transaxillary implantation of a permanent
      catheter-port system for intraarterial hepatic chemotherapy and determine their
      clinical relevance and specific management. SUBJECTS AND METHODS. Catheter-port
      systems were placed in 204 patients with liver tumors (86.7% from colorectal
      metastases). Under sonographic and fluoroscopic guidance, a 5.8-French catheter
      was placed in the hepatic artery and connected to a subcutaneous reservoir after
      embolization of the gastroduodenal and right gastric arteries. Floxuridine plus
      dexamethasone and systemic low-dose heparin were administered. During the follow
      up period, complications were classified as clinically not significant (type 1),
      clinically significant not requiring interruption of intrahepatic chemotherapy
      (type 2), clinically significant needing temporary suppression of intrahepatic
      chemotherapy (type 3), and clinically significant causing permanent suppression
      of intrahepatic chemotherapy (type 4). RESULTS: No complications occurred during
      the implantation procedures. The mean number of intrahepatic chemotherapy cycles
      was 8.1. The mean follow-up period was 270 days. Primary and secondary patency
      rates of the system were 71.6% and 91.2%, respectively. Temporary suppression of
      intrahepatic chemotherapy was necessary in 19.6% of the patients and definitive
      suppression, in 8.8%. Hepatic artery thrombosis, not recanalized by local
      thrombolysis, was the main cause of permanent intrahepatic chemotherapy
      interruption (4.4%). Catheter occlusions and cerebral complications were not
      observed. In 91.2% of the patients, intrahepatic chemotherapy could be completed.
      CONCLUSION: Percutaneous implantation of a removable and reimplantable catheter
      port system for intrahepatic chemotherapy can be a safe procedure to treat
      unresectable liver metastases from colorectal cancer. Technical and pharmacologic
      complications with variable clinical relevance occurred, and various specific
      management strategies were necessary to reduce their incidence.

PMID- 15149986
TI  - Whole-body 3D MR angiography of patients with peripheral arterial occlusive
      disease.
AB  - OBJECTIVE: We assessed the diagnostic performance of whole-body 3D contrast
      enhanced MR angiography in comparison with digital subtraction angiography (DSA)
      of the lower extremities in patients with peripheral arterial occlusive disease.
      SUBJECTS AND METHODS. Fifty-one patients with clinically documented peripheral
      arterial occlusive disease referred for DSA of the lower extremity arterial
      system underwent whole-body MR angiography on a 1.5-T MR scanner. Paramagnetic
      gadobutrol was administered and five contiguous stations were acquired with 3D T1
      weighted gradient-echo sequences in a total scanning time of 72 sec. DSA was
      available as a reference standard for the peripheral vasculature in all patients.
      Separate blinded data analyses were performed by two radiologists. Additional
      vascular disease detected by whole-body MR angiography was subsequently assessed
      on sonography, dedicated MR angiography, or both. RESULTS: All whole-body MR
      angiography examinations were feasible and well tolerated. AngioSURF-based whole
      body MR angiography had overall sensitivities of 92.3% and 93.1% (both 95%
      confidence intervals [CIs], 78-100%) with specificities of 89.2% and 87.6% (both
      CIs, 84-98%) and excellent interobserver agreement (kappa = 0.82) for the
      detection of high-grade stenoses. Additional vascular disease was detected in 12
      patients (23%). CONCLUSION: Whole-body MR angiography permits a rapid,
      noninvasive, and accurate evaluation of the lower peripheral arterial system in
      patients with peripheral arterial occlusive disease, and it may allow
      identification of additional relevant vascular disease that was previously
      undetected.

PMID- 15149987
TI  - Contrast-enhanced MR angiography of the foot: anatomy and clinical application in
      patients with diabetes.

PMID- 15149988
TI  - Conventional open surgery versus percutaneous catheter drainage in the treatment
      of cervical necrotizing fasciitis and descending necrotizing mediastinitis.
AB  - OBJECTIVE: The purpose of our study was to determine the clinical usefulness of
      percutaneous catheter drainage compared with conventional surgical drainage for
      cervical necrotizing fasciitis and descending necrotizing mediastinitis. SUBJECTS
      AND METHODS. Thirty-one patients with cervical necrotizing fasciitis and
      descending necrotizing mediastinitis were included. Twenty consecutive patients
      were treated by percutaneous catheter drainage. Catheters were introduced into
      the infected space from the neck, under the guidance of sonography and X-ray
      fluoroscopy. The results of the treatment were compared with those of 11 patients
      treated previously by surgical drainage. RESULTS: In the catheter group, no
      patient required supplementary surgical drainage. Mortality was 0% in both
      groups. Comparison of length of stay in the ICU, serial changes in C-reactive
      protein levels, duration of antibiotic therapy, and duration of mechanical
      ventilation all showed no statistically significant difference between groups.
      Secondary infection of the wound and positive culture of antibiotic-resistant
      bacteria were observed less frequently in the catheter group than in the open
      surgical group. The total use of plasma infusion and analgesics was significantly
      less in the catheter group than in the surgery group. Oral feeding was started
      significantly earlier in the catheter group than in the surgery group.
      CONCLUSION: Percutaneous catheter drainage for cervical necrotizing fasciitis and
      descending necrotizing mediastinitis was less invasive than conventional surgical
      drainage but produced a similar outcome.

PMID- 15149989
TI  - Balloon sphincteroplasty and transpapillary elimination of bile duct stones: 10
      years' experience.
AB  - OBJECTIVE: The usual way for interventional radiology to treat stones in the bile
      duct involves their extraction with Dormia baskets. The technique of dilating the
      sphincter with a balloon and the transpapillary elimination of the stones has
      only sporadically been reported in the literature. In this article, we describe
      our experience with this technique. MATERIALS AND METHODS: Between 1992 and 2001,
      we used this technique on 100 patients between the ages of 17 and 93 years (mean
      age, 68 years). The minimum diameter of the stones varied between 4 and 22 mm
      (mean size, 11 mm), and in 46 patients, only a single stone was seen. The stones
      were located in the common bile duct, and in 11 patients, intrahepatic stones
      were also observed. The approach was performed through a percutaneous biliary
      drainage tract in 48 patients, following the surgical tract of the Kehr tube in
      36 patients, through a surgical transcystic drainage catheter in 10 patients, and
      through a percutaneous cholecystostomy in six patients. RESULTS: The procedure
      was successful in 95% of the patients. The morbidity rate was 5%, and the
      procedure did not produce mortality in any of the cases. Eighty-nine patients
      required one session, 10 patients required two sessions, and the remaining
      patient required five sessions. The mean period of hospitalization after the
      procedure was 5.5 days (range, 1-40 days). CONCLUSION: Balloon sphincteroplasty
      and transpapillary elimination of bile duct stones is an effective and safe
      technique.

PMID- 15149990
TI  - Thermal protection during radiofrequency ablation.

PMID- 15149991
TI  - Primary gastrointestinal stromal tumors in the omentum and mesentery: CT findings
      and pathologic correlations.
AB  - OBJECTIVE: This study was undertaken to describe the CT features of primary
      gastrointestinal stromal tumors in the omentum and mesentery and to identify any
      pathologic correlation. CONCLUSION: On contrast-enhanced CT, primary
      gastrointestinal stromal tumors in the omentum and mesentery are usually well
      defined, huge masses that contain large areas of low-attenuation necrosis and
      hemorrhage and that lack central gas.

PMID- 15149993
TI  - Value of curved planar reformations in MDCT of abdominal pathology.

PMID- 15149992
TI  - Preoperative MRI of rectal cancer with and without rectal water filling: an
      intraindividual comparison.
AB  - OBJECTIVE: The purpose of our study was to determine if a rectal distention using
      warm water may improve the accuracy of MRI for the preoperative staging of rectal
      carcinoma. SUBJECTS AND METHODS. Sixty-two patients with surgically proven rectal
      carcinomas underwent pelvic MRI before and after a rectal distention by warm
      water. Four radiologists, who were blinded to the study, reviewed each set of T1-
      and T2-weighted axial images obtained before and after the rectal distention and
      scored the image of the tumor. The accuracies for determining the tumor
      penetration of the outer wall of the rectum and the regional lymph node
      involvement were compared by analyzing the area under the receiver operating
      characteristic curve (A(z)). RESULTS: For all reviewers, the tumor depiction
      scores were significantly higher in the distended images (3.8-3.9 for reviewers 1
      4) than in the nondistended images (3.0-3.2) (p < 0.01). For determining the
      outer wall penetration, the accuracy of the three reviewers was significantly
      higher with the rectal distention images than with the nondistended images (p <
      0.05). The mean accuracy of the all reviewers was significantly better with the
      distended images (A(z) = 0.922) than with the nondistended images (A(z) = 0.841)
      (p < 0.05). For determining the presence of regional lymph node involvement, all
      the reviewers came to similar conclusions in analyzing the two image sets.
      CONCLUSION: Rectal distention by water filling may improve the depiction of a
      primary rectal tumor and the assessment accuracy of a perirectal tumor extension,
      but it does not improve the accuracy for determining the presence of regional
      lymph node involvement.

PMID- 15149994
TI  - Abdominal lymphangiomas: imaging features with pathologic correlation.

PMID- 15149995
TI  - CT of nontraumatic abdominal fluid collections after initial fluid resuscitation
      of patients with major burns.
AB  - OBJECTIVE: The purpose of this study was to describe the presence and CT
      distribution of nontraumatic fluid collections and edema in the abdomen and
      pelvis after initial fluid resuscitation of patients with major (>/=="
      BORDER="0"> 25% total body surface area) thermal burns. CONCLUSION: Awareness of
      the presence and expected CT distribution of nontraumatic fluid after initial
      fluid resuscitation in patients with major burns can assist the radiologist in
      differentiating such collections from those caused by mechanical trauma.

PMID- 15149996
TI  - Diagnosing biliary complications of orthotopic liver transplantation with
      mangafodipir trisodium-enhanced MR cholangiography: comparison with conventional
      MR cholangiography.
AB  - OBJECTIVE: This study was designed to determine whether the addition of
      mangafodipir trisodium-enhanced MRI could improve the image quality,
      visualization of ductal structures, and diagnostic confidence provided by
      conventional T2-based MR cholangiography (MRC) in patients with suspected biliary
      complications after orthotopic liver transplantation. SUBJECTS AND METHODS. Our
      study group consisted of 25 consecutive patients who were referred for MR
      evaluation of clinically suspected biliary complications after orthotopic liver
      transplantation. Conventional MRC in the axial and coronal planes was performed
      in each patient, followed by fat-suppressed volumetric gradient-echo imaging in
      the same planes both before and after the IV administration of mangafodipir
      trisodium. Imaging was performed in all patients until the contrast agent was
      seen in the bowel. Images were then graded for quality, visualization of bile
      ducts and anastomoses, presence of significant stricture or leak, and level of
      diagnostic confidence. RESULTS: Mangafodipir trisodium-enhanced MRC tended to
      outperform conventional MRC in overall image quality and extrahepatic duct
      visualization; it was also more effective in delineating biliary anastomoses, and
      the difference was statistically significant (p < 0.001). All 25 enhanced
      examinations were considered diagnostic. Diagnostic confidence was scored as poor
      or lacking in 14 of the conventional MRC examinations for biliary stenosis and in
      12 examinations for biliary leak. CONCLUSION: Enhancement with mangafodipir
      trisodium improves the performance of MRC for the detection and exclusion of
      biliary abnormalities after orthotopic liver transplantation. Future
      investigations should compare the performance of mangafodipir trisodium-enhanced
      MRC with the performance of more invasive techniques.

PMID- 15149997
TI  - Characterization of focal liver lesions in real time using harmonic imaging with
      high mechanical index and contrast agent levovist.
AB  - OBJECTIVE: The aim of this study was to characterize focal hepatic lesions using
      agent detection imaging and Levovist. MATERIALS AND METHODS: Sixty-five patients
      (21 male and 44 female; age range, 8-82 years; mean +/- standard deviation, 58.1
      +/- 14.5 years) were independently evaluated by two observers in a blinded manner
      using stored sonographic images. Seventy-five lesions were found: 15
      hepatocellular carcinomas, nine focal nodular hyperplasias, two adenomas, 21
      hemangiomas, 23 metastases, and five regenerative nodules. Nine patients were
      excluded (six because of technical failures, three with unproven diagnoses). New
      high-mechanical-index software was used to reveal power harmonic responses from
      contrast microbubble destruction. After a venous bolus injection of 4 g of
      Levovist at a strength of 400 mg/mL, delayed imaging was used to study lesion
      enhancement in the arterial, portal, and parenchymal phases. Two comparisons were
      made. The first was between the B-mode image and the first contrast-enhanced
      image after the flash. The second was between color Doppler sonograms and real
      time contrast-enhanced perfusion images. RESULTS: Contrast-enhanced images after
      the flash and real-time contrast-enhanced images revealed more information for
      the characterization of the lesion than did gray-scale and color Doppler images
      (p < 0.0001, Wilcoxon's signed rank test). Different types of lesions showed
      statistically significant differences in enhancement during each of the three
      vascular phases (p < 0.005, Kruskal-Wallis test). Lesions with lower contrast
      enhancement were metastases and regenerating nodules. Good agreement was present
      between the two observers; differences were not statistically significant (p >
      0.05). CONCLUSION: Agent detection imaging with Levovist increased diagnostic
      confidence in the characterization of focal hepatic lesions as compared with
      standard sonography.

PMID- 15149998
TI  - MRI of gallstones with different compositions.
AB  - OBJECTIVE: Gallstones are usually recognized on MRI as filling defects of
      hypointensity. However, they sometimes may appear as hyperintensities on T1
      weighted imaging. This study investigated how gallstones appear on MRI and how
      their appearance influences the detection of gallstones. MATERIALS AND METHODS:
      Gallstones from 24 patients who had MRI performed before the removal of the
      gallstones were collected for study. The gallstones were classified either as
      cholesterol gallstone (n = 4) or as pigment gallstone (n = 20) according to their
      gross appearance and based on analysis by Fourier transform infrared
      spectroscopy. MRI included three sequences: single-shot fast spin-echo T2
      weighted imaging, 3D fast spoiled gradient-echo T1-weighted imaging, and in-phase
      fast spoiled gradient-echo T1-weighted imaging. The signal intensity and the
      detection rate of gallstones on MRI were further correlated with the character of
      the gallstones. RESULTS: On T1-weighted 3D fast spoiled gradient-echo images,
      most of the pigment gallstones (18/20) were hyperintense and all the cholesterol
      gallstones (4/4) were hypointense. The mean ratio of the signal intensity of
      gallstone to bile was (+/- standard deviation) 3.36 +/- 1.88 for pigment
      gallstone and 0.24 +/- 0.10 for cholesterol gallstone on the 3D fast spoiled
      gradient-echo sequence (p < 0.001). Combining the 3D fast spoiled gradient-echo
      and single-shot fast spin-echo sequences achieved the highest gallstone detection
      rate (96.4%). CONCLUSION: Based on the differences of signal intensity of
      gallstones, the 3D fast spoiled gradient-echo T1-weighted imaging was able to
      diagnose the composition of gallstones. Adding the 3D fast spoiled gradient-echo
      imaging to the single-shot fast spin-echo T2-weighted sequence can further
      improve the detection rate of gallstones.

PMID- 15149999
TI  - Hepatic adenoma.

PMID- 15150000
TI  - Accessory renal arteries are not related to hypertension risk: a review of MR
      angiography data.
AB  - OBJECTIVE: It has been hypothesized that accessory renal arteries are related to
      the risk of hypertension. Our goal was to determine the prevalence of accessory
      renal arteries in hypertensive patients using MR angiography and to assess the
      relationship between accessory renal arteries and hypertension risk. MATERIALS
      AND METHODS: From 1996 to 2002, 185 hypertensive patients underwent MR
      angiography of the renal arteries at our institution for assessment of renal
      artery stenosis. MR angiograms were obtained using a 1.5-T magnet, IV gadolinium,
      and 3D gradient-echo sequences. Interpretations of the MR angiograms were
      retrospectively reviewed. RESULTS: Of 185 hypertensive patients, 45 (24%) showed
      accessory renal arteries. Of these 45 patients, nine (20%) showed renal artery
      stenosis and 36 (80%) showed no significant stenosis. Of the 140 patients with a
      single renal artery, 42 (30%) showed renal artery stenosis and 98 (70%) showed no
      stenosis. The odds ratio of renal artery stenosis in the accessory renal artery
      group versus the single renal artery group was 0.58 (95% confidence interval,
      0.26-1.3%), which is not statistically significant at a power of 0.85 (chi(2) =
      1.705; p = 1.0). CONCLUSION: We found no statistically significant difference in
      the prevalence of renal artery stenosis between patients with accessory renal
      arteries and those without accessory renal arteries. Assuming that the presence
      of two separate causes of hypertension in the same patient would be unlikely,
      this finding implies that accessory renal arteries are a vascular anomaly and not
      a direct cause of hypertension. The findings are potentially relevant in refuting
      the theory of accessory renal arteries as an anatomically treatable cause of
      hypertension.

PMID- 15150001
TI  - Contrast-enhanced second-harmonic sonography in the detection of pseudocapsule in
      renal cell carcinoma.
AB  - OBJECTIVE: Our purpose was to assess the capacity of contrast-enhanced second
      harmonic sonography to detect a pseudocapsule in renal masses compared with
      conventional gray-scale sonography. SUBJECTS AND METHODS. Thirty-two patients
      with 40 renal masses suspicious for renal cancer (mean diameter, 3.1 cm) were
      prospectively studied with contrast-enhanced second-harmonic sonography during IV
      administration of a second-generation sonographic contrast agent. The sonographic
      criteria for the presence of a pseudocapsule were a peritumoral hypoanechoic halo
      on conventional gray-scale imaging and a rim of perilesional enhancement,
      increasing in the tardive phase of the examination, on contrast-enhanced second
      harmonic imaging. Multiphasic helical CT or dynamic MRI or both were performed in
      all patients. RESULTS: Final diagnoses of the 40 renal masses were as follows:
      hemorrhagic cysts, five; angiomyolipomas, four; lymphomas, four; metastasis from
      lung cancer, one; and renal cell carcinomas (RCCs), 26. Histologic diagnosis of
      RCC was surgically obtained in all patients. Nephron-sparing surgery was
      performed in 12 of 26 RCCs, and radical nephrectomy was performed in the
      remaining 14. At pathologic examination, pseudocapsule was found in 14 (53.8%) of
      26 RCCs. On conventional sonography, the presence of a pseudocapsule was detected
      in 3 of 14 RCCs (sensitivity, 21%). Sonographic contrast-enhanced harmonic
      imaging revealed the presence of pseudocapsule in 12 of 14 RCCs (sensitivity,
      85.7%). In the remaining 12 RCCs with either absent or extensive neoplastic
      infiltration of pseudocapsule seen at pathologic evaluation, pseudocapsule was
      not visible on either conventional or contrast-enhanced second-harmonic
      sonography. The pseudocapsule was not visible in any of the 14 noncancerous renal
      masses on either conventional or contrast-enhanced sonography. CONCLUSION:
      Sonographic contrast-specific imaging with a second-generation contrast agent is
      effective in improving the sonographic visualization of tumoral pseudocapsule.
      This finding could be useful both in the sonographic diagnosis and in the choice
      of conservative surgery for renal cell carcinoma. The potential role of second
      harmonic contrast-enhanced sonography in the management of renal cell carcinoma
      should be investigated in larger series and compared with the findings of state
      of-the-art MRI and CT.

PMID- 15150002
TI  - Sonographic, CT, and MRI findings of endometrial stromal sarcoma located in the
      myometrium and associated with peritoneal inclusion cyst.

PMID- 15150004
TI  - MRI of five patients with mitochondrial neurogastrointestinal encephalomyopathy.
AB  - OBJECTIVE: The purpose of this study was to retrospectively review MR images of
      the brain in five patients diagnosed with mitochondrial neurogastrointestinal
      encephalomyopathy. CONCLUSION: Our research supports previously reported findings
      of confluent abnormal cerebral white matter in patients with mitochondrial
      neurogastrointestinal encephalomyopathy. In contrast to prior studies, our cohort
      of five patients showed that involvement of the corpus callosum as well as the
      capsular white matter, basal ganglia, thalami, midbrain, pons, and cerebellar
      white matter is not rare and does not preclude the diagnosis of mitochondrial
      neurogastrointestinal encephalomyopathy.

PMID- 15150005
TI  - Cerebellar endometriosis.

PMID- 15150003
TI  - Papillary serous adenocarcinoma of the endometrium: CT-pathologic correlation.

PMID- 15150006
TI  - Routine use of gradient-echo MRI to screen for cerebral amyloid angiopathy in
      elderly patients.
AB  - OBJECTIVE: The objective of this study was to evaluate the routine use of
      gradient-refocused echo MRI sequences in the detection of cortical cerebral
      microbleeding suggestive of cerebral amyloid angiopathy in elderly patients (> 70
      years old). CONCLUSION: The addition of gradient-refocused echo sequences to
      routine brain MRI resulted in the identification of cerebral amyloid angiopathy
      related microbleeding in 15.5% of elderly patients. In most (86.7%) of these
      patients with positive findings, cerebral amyloid angiopathy was not suspected
      clinically, and 46.7% of these patients were undergoing anticoagulant or aspirin
      therapy, placing them at an increased risk of recurrent intracranial hemorrhage
      and catastrophic stroke.

PMID- 15150007
TI  - "William Tell" injury: MDCT of an arrow through the head.

PMID- 15150008
TI  - Oral contrast agents for CT of abdominal trauma in pediatric patients: a
      comparison of dilute hypaque and water.
AB  - OBJECTIVE: Dilute Hypaque Sodium is generally well accepted as an oral contrast
      agent for CT of pediatric patients who have experienced recent blunt abdominal
      trauma. However, Hypaque can cause complications. Using water as a substitute
      contrast agent eliminates these potential complications. The purpose of our study
      was to compare the performance of water with that of dilute Hypaque as an oral
      contrast agent. Our hypothesis was that we would find no significant difference
      in performance between the two agents in defining anatomic details of the hollow
      gastrointestinal tract. MATERIALS AND METHODS: We performed a retrospective
      review of 74 CT scans obtained in infants and children who had received blunt
      abdominal trauma, scoring the quality of visualization of bowel structures, the
      presence of non-bowel-related findings, and the confidence level in making each
      assessment. The date range of the scans reviewed overlapped with the period in
      which the oral contrast material used for scanning such patients was switched
      from dilute Hypaque to water. Of the 74 CT scans that we reviewed, 53 were
      obtained with dilute Hypaque and 21 were obtained with water. The sex
      distribution between the two groups was compared using a chi-square test, whereas
      the mean age was compared using a two-sample two-sided Student's t test. A two
      sample one-sided Student's t test of equivalence was used to analyze the data.
      RESULTS: Sex distribution for the two groups of patients was not significantly
      different (69.81% of the group who received dilute Hypaque were boys; 68.18% of
      the group who received water were boys). Furthermore, the difference in the mean
      age for the two groups was not statistically significantly (dilute Hypaque group,
      8.86 years; water group, 10.18 years). No statistically significant difference in
      performance of the contrast agents was found with respect to the detection of
      intraabdominal abnormality. As an oral contrast material, water performed as well
      as dilute Hypaque in facilitating visualization of all intraabdominal anatomic
      structures. CONCLUSION: In defining anatomic details of the hollow
      gastrointestinal tract, water is as effective as dilute Hypaque as an oral
      contrast agent for CT in the setting of acute blunt abdominal trauma in pediatric
      patients.

PMID- 15150009
TI  - Wegener's granulomatosis complicated by central diabetes insipidus in a pediatric
      patient.

PMID- 15150010
TI  - CT detection of acute myocardial infarction.
AB  - OBJECTIVE: The aim of this study was to evaluate the ability of contrast-enhanced
      CT to detect acute myocardial infarction (MI), which has not been systematically
      assessed. On contrast-enhanced helical chest CT, we retrospectively identified 18
      patients (10 women, eight men; mean age, 66 years) with an initial MI. Each
      patient underwent contrast-enhanced single-detector helical chest CT within 1
      month after the MI between March 2001 and June 2002. CONCLUSION: Acute MI is
      detectable on contrast-enhanced chest CT as an area of decreased left ventricular
      myocardial enhancement in a specific coronary arterial distribution.

PMID- 15150011
TI  - Eight cases of severe acute respiratory syndrome presenting as round pneumonia.
AB  - OBJECTIVE: The purpose of this study was to describe the radiographic findings
      and evolution of round pneumonia found in eight patients with confirmed severe
      acute respiratory syndrome (SARS). CONCLUSION: SARS may present as round
      pneumonia on chest radiographs initially or during the treatment course. It may
      remain unchanged for up to 9 days before evolution to ill-defined air-space
      opacities. Radiologists and physicians should consider the possibility of "SARS
      pneumonia" when spherical air-space opacities are noted on chest radiographs of
      febrile patients.

PMID- 15150012
TI  - Single-detector helical CT in PET-CT: assessment of image quality.
AB  - OBJECTIVE: CT in positron emission tomography (PET)-CT imaging is often performed
      as a single scan from the base of the skull to the groin, potentially resulting
      in degradation of the quality of CT scans depending on the position of the
      patient's arms and mode of breathing and the use and timing of IV contrast
      injection. The aim of our study was to assess the impact of artifacts on the
      diagnostic quality of CT scans using a single-detector helical CT scanner in PET
      CT imaging. MATERIALS AND METHODS: Two radiologists retrospectively evaluated the
      diagnostic image quality of CT scans obtained with PET-CT in 81 patients with
      lymphoma. The severity of the artifacts related to the position of the patient's
      arms beside the body, the influence of breathing motion, and the presence of
      contrast material in the upper thoracic veins were ranked using a 4-point scale.
      RESULTS: Performing CT with the patient's arms positioned beside the body
      resulted in streak artifacts, predominantly in the upper abdomen, that were
      graded as mild in 22%, moderate in 40%, and severe in 38% of the scans. A
      patient's weight significantly correlated with the degree of severity of the
      artifacts (p < 0.05). Shallow breathing by the patient during scanning caused
      blurring and double-imaging, again predominantly in the upper abdomen, that were
      graded as mild in 23%, moderate in 49%, or severe in 28% of the scans. In 84% of
      the CT scans obtained with IV contrast material, the image quality of the upper
      thoracic region was moderately (27%) or severely (57%) degraded by streak
      artifacts from highly concentrated contrast material in the upper thoracic veins.
      CONCLUSION: The use of a single-detector CT scanner in whole-body PET-CT
      decreases the image quality of CT scans because of streak artifacts that occur
      predominantly in scans of the upper abdomen. Scanning with the patient's arms
      raised eliminates the streak artifacts in scans of the abdominal region. With the
      new generation of PET-CT devices equipped with MDCT scanners, breathing motion
      artifacts can be expected to be eliminated if protocols for breath-hold CT are
      applied. Reversing the direction of CT scanning allows one to avoid imaging the
      thoracic region at a time when undiluted IV contrast material is still present in
      the upper thoracic veins.

PMID- 15150013
TI  - PET-CT of extranodal lymphoma.

PMID- 15150014
TI  - Teflon injection for vocal cord paralysis: false-positive finding on FDG PET-CT
      in a patient with non-small cell lung cancer.

PMID- 15150015
TI  - A simple method for importing multiple image files into PowerPoint.
AB  - OBJECTIVE: We developed a method for automatically inserting a large number of
      images into a PowerPoint presentation document. CONCLUSION: We designed, tested,
      and now routinely use a simple macro program for importing all images contained
      in a single directory into a PowerPoint presentation. The complete text of the
      macro code is included in this article, and readers are encouraged to experiment
      with it.

PMID- 15150016
TI  - Cryotherapy and percutaneous ablation.

PMID- 15150017
TI  - Dose levels in pregnancy.

PMID- 15150018
TI  - Improved sensitivity of mammography with computer-aided detection.

PMID- 15150019
TI  - How not to assess computer-aided detection for mammography.

PMID- 15150020
TI  - Colorectal cancer imaging.

PMID- 15150021
TI  - Regarding "fish" or "fish mouth" vertebrae.

PMID- 15150022
TI  - Open low-field-strength MRI of the shoulder is not so bad.

PMID- 15150023
TI  - Imaging of pure primary ovarian choriocarcinoma.

PMID- 15150024
TI  - Pelvic lipomatosis detected on bone scintigraphy.

PMID- 15150025
TI  - Amyloidoma of Meckel's cave: a rare cause of trigeminal neuralgia.

PMID- 15150027
TI  - Acute torsion of wandering spleen: MRI findings.

PMID- 15150026
TI  - Hyperbaric oxygen therapy for air embolism complicating CT-guided needle biopsy
      of the lung.

PMID- 15150028
TI  - CT and MRI findings of primary non-Hodgkin's lymphoma of the common bile duct
      mimicking cholangiocarcinoma.

PMID- 15150030
TI  - "All-inside" meniscal repair devices: an experimental study in the goat model.
AB  - BACKGROUND: Although the use of "all-inside" absorbable meniscal repair devices
      has become popular, numerous complications have been reported. The authors
      applied their well-established goat model to evaluate three "all-inside" meniscal
      repair devices. METHODS: A "tear" was created in the medial meniscus of both
      knees in 26 goats. The animals were randomized into four groups, and the meniscus
      was treated as follows: (A) meniscal repair with Mitek Fastner, (B) meniscal
      repair with BioStinger, (C) meniscal repair with Mitek Clearfix Screw, and (D) no
      repair. All animals were sacrificed at 6 months postoperatively, and all
      specimens were carefully evaluated and results recorded and compared with
      historical results of meniscal repair with suture in this same animal model.
      RESULTS: Meniscal repair results with all three all-inside devices studied were
      inferior to suture repair. Chondral injury was present in 75% to 100% of repairs
      with all-inside devices and none of the control specimens. DISCUSSION: /
      CONCLUSION: Although new all-inside meniscal repair devices are relatively quick
      and easy, results may not be as good as with traditional suture techniques. The
      high rate of chondral injury associated with these devices in the goat model is
      worrisome for chondral damage in humans, especially in patients with smaller or
      tighter knees.

PMID- 15150031
TI  - Initial fixation strength of flexible all-inside meniscus suture anchors in
      comparison to conventional suture technique and rigid anchors: biomechanical
      evaluation of new meniscus refixation systems.
AB  - BACKGROUND: The newest generation of meniscus repair devices is designed to
      combine the benefits of the all-inside technique with the biomechanical
      properties of sutures. HYPOTHESIS: New flexible all-inside suture anchors have
      better fixation strength than rigid anchors, but there is no difference when
      compared to conventional horizontal and vertical mattress sutures. STUDY DESIGN:
      Controlled laboratory study. METHODS: In fresh-frozen bovine menisci, initial
      fixation strength, stiffness, and failure mode of different meniscus fixation
      techniques (FastT-Fix, RapidLoc, Meniscus Arrow, horizontal and vertical 2.0
      Ethibond sutures) were evaluated in a computer-based materials testing machine at
      a rate of 12.5 mm/sec. RESULTS: The vertical and horizontal FastT-Fix suture
      anchors were the strongest devices with regard to pullout strength, with no
      significant difference compared to the vertical 2-0 Ethibond sutures. Horizontal
      sutures, Meniscus Arrow, and RapidLoc had significantly lower pullout strength.
      Vertical and horizontal FastT-Fix suture anchors showed significantly higher
      stiffness than the other devices. CONCLUSIONS: Biomechanical properties of
      flexible all-inside meniscus anchors (FastT-Fix) are comparable to conventional
      vertical suture techniques. Characteristics of the flexible RapidLoc are
      comparable to rigid anchors (Meniscus Arrow). CLINICAL RELEVANCE: From the
      biomechanical point of view, flexible all-inside meniscus refixation devices are
      an alternative to conventional suture techniques and rigid meniscus anchors.

PMID- 15150032
TI  - The effect of growth factors on biomechanical properties of the bone-patellar
      tendon-bone graft after anterior cruciate ligament reconstruction: a canine model
      study.
AB  - BACKGROUND: No studies have dealt with the effect of growth factors on the free
      tendon autograft in anterior cruciate ligament reconstruction. HYPOTHESIS:
      Application of exogenous transforming growth factor-beta and epidermal growth
      factor may affect the structural properties and histology of the bone-patellar
      tendon-bone autograft after anterior cruciate ligament reconstruction. STUDY
      DESIGN: Controlled laboratory study. METHODS: Twenty dogs underwent anterior
      cruciate ligament reconstruction with the autogenous bone-patellar tendon-bone
      graft in bilateral knees. In 10 animals, 12 ng transforming growth factor-beta
      and 300 ng epidermal growth factor mixed with fibrin sealant of 0.6 mL were
      applied to the left knee. In the remaining 10 dogs, fibrin sealant alone was
      applied to the left knee. No additional treatments were applied to the right
      knee. RESULTS: The growth factor application increased the stiffness and maximum
      failure load of the femur-graft-tibia complex at 12 weeks (P =.016 and P =.012,
      respectively); the sham treatment did not significantly affect them.
      Histologically, most of the cells in the grafts treated with growth factors had
      spindle-shaped nuclei; cells in the other grafts had round-shaped nuclei.
      CONCLUSIONS: Application of transforming growth factor-beta and epidermal growth
      factor improves the structural properties of the autograft after anterior
      cruciate ligament reconstruction in the canine model. CLINICAL RELEVANCE:
      Application of growth factors is a possible strategy to prevent graft
      deterioration in anterior cruciate ligament reconstruction.

PMID- 15150033
TI  - The influence of locally applied platelet-derived growth factor-BB on free tendon
      graft remodeling after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Ligaments and tendons do not gain mechanical properties of the native
      tissue after injury or grafting. PURPOSE: To determine the influence of platelet
      derived growth factor on tendon graft remodeling. STUDY DESIGN: Laboratory animal
      study. METHODS: Forty-eight sheep underwent anterior cruciate ligament
      reconstruction and were sacrificed after 3, 6, 12, and 24 weeks. In 6 animals at
      each time point, platelet-derived growth factor was locally delivered via coated
      sutures. After mechanical testing, tissue samples were taken for histologic,
      immunohistochemical, and electron microscopy evaluations. RESULTS: With platelet
      derived growth factor treatment, cross-sectional area was significantly lower at
      3 and 12 weeks. Load to failure was significantly higher at 6 weeks. Tensile
      stress was significantly higher at 3 and 12 weeks. Crimp length was significantly
      higher at 3 and 6 weeks. Vascular density was significantly higher at 6 weeks.
      Electron microscopy showed a significantly higher collagen fibril amount at 12
      weeks. Differences in these parameters at other time points were not significant.
      CONCLUSIONS: There were alterations in several but not all time points. The local
      application of platelet-derived growth factor alters the tissue's mechanical
      properties during free tendon graft remodeling after anterior cruciate ligament
      reconstruction. Growth factors present a promising tool toward the complete
      mechanical restitution of a healing ligament substitute.

PMID- 15150034
TI  - Humeral torque in professional baseball pitchers.
AB  - BACKGROUND: Spontaneous fracture of the humeral shaft in throwers is a rare but
      well-known phenomenon. Although it has been hypothesized that the biomechanics of
      the throw cause such fractures, it is not clear how or when the fractures occur
      in the pitching motion. METHODS: The torque acting about the long axis of the
      humerus was calculated in 25 professional baseball pitchers throwing in game
      situations. RESULTS: Peak humeral axial torque reached a mean value of 92 +/- 16
      Nm near the time of maximum shoulder external rotation at the end of the cocking
      phase. This torque tended to externally rotate the distal end of the humerus
      relative to its proximal end. The direction of the torque was consistent with the
      external rotation spiral fractures of the humerus noted to occur in throwers. The
      magnitude of the peak humeral torque averaged 48% of the theoretical torsional
      strength of the humerus, suggesting that repetitive stress plays a role in
      humeral shaft fractures. CONCLUSIONS: Fractures are most likely to occur near the
      time of maximum shoulder external rotation when humeral torque peaks. Pitchers
      whose elbows were more extended at stride foot contact tended to have lower peak
      humeral torques.

PMID- 15150035
TI  - Development of a new activity score for the evaluation of ankle instability.
AB  - BACKGROUND: Tegner and Lysholm described their generally acknowledged activity
      score in 1985. It was originally tested for knee ligament injuries, but for the
      past 17 years it has been used for other joint evaluations as well. The
      development of already existing and new kinds of sports, differences between knee
      and ankle loading, and different injury rates provided reasons for developing an
      ankle-specific activity score. HYPOTHESIS: The new score should have a higher
      reliability, validity, and sensitivity than the Tegner score when evaluating
      ankle-related activity changes. STUDY DESIGN: Methodological study. METHODS:
      Fifty-three sports, 3 working activities, and 4 general activities were inserted
      into a 0-to-10 category system based on the rankings of a 7 x 2-point pre
      evaluation system, followed by a direct comparison with the Tegner score and
      reliability, validity, and sensitivity testing on 2 different patient
      populations. RESULTS: In direct comparison, there is a strong overall correlation
      of the 2 activity-scoring systems (r = 0.7565), but the ankle activity score
      proved to be different from the Tegner score in the higher categories, especially
      in the top 4 ankle score categories (r = 0.1450). Further tests demonstrated the
      high reliability (1.00) of the new score. Analysis of variance proved that
      activity changes measured by the ankle score correspond well to the difference
      between the patients' subjective results and their Karlsson functional scores (P
      =.0119). This is not the case when we measure ankle activity changes using the
      knee-specific Tegner score (P =.0987). Furthermore, ankle score differences
      spread over a wider range (-1.18 +/- 2.12) than did Tegner score differences (
      0.68 +/- 1.29), which demonstrates the higher sensitivity of the new score.
      CONCLUSIONS: Based on these results, the new ankle activity score could be a
      better complement in the complex evaluation of ankle instability.

PMID- 15150036
TI  - Temperature along the axillary nerve during radiofrequency-induced thermal
      capsular shrinkage.
AB  - BACKGROUND: There have been reports of axillary nerve palsy after thermal
      capsular shrinkage with radiofrequency energy-generating devices. The exact cause
      of this is unknown. HYPOTHESIS: The temperature of the axillary nerve increases
      during shoulder capsular shrinkage at various degrees of shoulder abduction.
      STUDY DESIGN: Laboratory study. METHODS: Fifteen cadaveric shoulders had
      fiberoptic thermometer probes placed at various points along the axillary nerve
      and major branches under the capsule. The shoulders underwent thermal capsular
      shrinkage with a radiofrequency energy-inducing device at various positions of
      abduction. RESULTS: With the arm at the side, temperatures above 50 degrees C (56
      degrees -61 degrees C) were evident along the teres minor branch of the axillary
      nerve in 4 of 6 specimens. The increase in temperature was noted in the middle to
      posterior aspect of the inferior capsule. At 45 degrees of abduction, 4 of 5
      shoulders demonstrated increases in temperature greater or equal to 50 degrees.
      Three of 4 shoulders tested at 90 degrees of abduction revealed similar
      temperature increases. CONCLUSIONS: The arthroscopic technique of thermal
      capsular shrinkage causes an increase in the temperature of the axillary nerve
      and its branches in 11 of 15 cadaveric specimens tested at various arm positions
      particularly affected is the teres minor branch. CLINICAL RELEVANCE: Orthopaedic
      surgeons using the radiofrequency device for thermal capsular shrinkage need to
      be aware of the possible increase in temperature along the axillary nerve and its
      branches during this procedure. The clinical effect of this type of increase on
      the nerve is unknown.

PMID- 15150037
TI  - Promoting the proliferative and synthetic activity of knee meniscal
      fibrochondrocytes using basic fibroblast growth factor in vitro.
AB  - BACKGROUND: Meniscal tears situated within the inner avascular region do not heal
      despite suturing. New approaches need to be developed to augment surgical repair.
      HYPOTHESIS: To demonstrate that basic fibroblast growth factor, used as a single
      agent or in combination with serum, stimulates the activity of fibrochondrocytes
      by enhancing proliferation and extracellular matrix synthesis in all meniscal
      zones, including the inner (avascular) zone of the meniscus. STUDY DESIGN:
      Controlled laboratory study. METHODS: Monolayer cell cultures were prepared from
      the inner, middle, and outer zones of the lateral meniscus. Various
      concentrations of basic fibroblast growth factor were used in the presence or
      absence of 10% fetal calf serum. The authors measured the uptake of radiolabeled
      thymidine to assess cell proliferation and radioactive sulfur and proline to
      assess extracellular matrix formation. RESULTS: Overall, basic fibroblast growth
      factor-stimulated cells from all meniscal zones to proliferate and to form new
      extra-cellular matrix (P <.05). The basic fibroblast growth factor (in the
      absence of serum) increased DNA formation and protein synthesis by cells from the
      inner meniscal zone by 7- and 15-fold, respectively (P <.001). CONCLUSIONS: These
      results indicate that meniscal cells and, more important, cells from the
      avascular zone are capable of responding favorably to the addition of basic
      fibroblast growth factor by expressing their intrinsic potential to proliferate
      and generate new extracellular matrix. CLINICAL RELEVANCE: The results suggest
      that it may be possible to augment surgical repair of the meniscus in the future.

PMID- 15150038
TI  - A prospective study of kitesurfing injuries.
AB  - BACKGROUND: To date, the pattern and rate of kitesurfing injuries are largely
      unclear. HYPOTHESIS: The pattern and rate of kitesurfing injuries are comparable
      to that of contact sports such as football and soccer. STUDY DESIGN: Prospective
      study. METHODS: The study was conducted over a 6-month period of 1 season and
      included 235 kitesurfers. RESULTS: The number of self-reported injuries was 124,
      for an overall self-reported injury rate of 7 per 1000 hours of practice. One
      fatal accident (polytrauma) and 11 severe injuries occurred during the study
      period (2 knee ligament injuries and 9 fractures at various sites). The most
      commonly injured sites were the foot and ankle (28%), skull (14%), chest (13%),
      and knee (13%). Fifty-six percent of the injuries were attributed to the
      inability to detach the kite from the harness in a situation involving loss of
      control over the kite. There was a tendency for athletes using a quick-release
      system to sustain fewer injuries than athletes without such a release system.
      CONCLUSION: Kitesurfing can be considered a high-risk sport. CLINICAL RELEVANCE:
      The use of a quick-release system that enables the surfers to detach the kite in
      case of an accident might aid in the prevention of injuries.

PMID- 15150039
TI  - Long-term functional and anatomical follow-up of early detected spondylolysis in
      young athletes.
AB  - BACKGROUND: Spondylolysis defects detected by nuclear scintigraphy but not by
      plain radiographs represent early lesions. Functional outcome and eventual bony
      union of these defects are unknown. HYPOTHESIS: Defects with greater degree of
      healing shortly after treatment will proceed to full bony union and better long
      term functional outcome. STUDY DESIGN: Longitudinal cohort study. METHODS: Forty
      young athletes with early detected spondylolysis (radiograph negative, nuclear
      scintigraphy positive) were divided into 3 stages of healing by computed
      tomography scan. Functional outcome was assessed 7 to 11 years later using the
      low back outcome score and other factors. Degree of bony healing was assessed in
      volunteers. RESULTS: Thirty-two of 40 subjects (80%) completed the survey. Twenty
      nine of 32 (91%) had good or excellent low back outcome scores. None required
      spinal fusion, but 1 required partial diskectomy. Functional outcome did not
      differ based on initial computed tomography results. Radiographic follow-up was
      obtained in 11 volunteers. None of the 7 bilateral defects healed, and 3 of these
      progressed to grade 1 spondylolisthesis. All 4 unilateral defects healed fully
      with bone. CONCLUSIONS: Most young athletes conservatively treated for early
      spondylolysis maintain good functional outcome up to 11 years later. Unilateral
      defects can undergo full bony healing but may take longer than 12 weeks.
      Bilateral defects may undergo further degeneration and slip with time.

PMID- 15150040
TI  - Nandrolone decanoate and load increase remodeling and strength in human
      supraspinatus bioartificial tendons.
AB  - BACKGROUND: To date, no studies document the effect of anabolic steroids on
      rotator cuff tendons. STUDY DESIGN: Controlled laboratory study. HYPOTHESIS:
      Anabolic steroids enhance remodeling and improve the biomechanical properties of
      bioartificially engineered human supraspinatus tendons. METHODS: Bioartificial
      tendons were treated with either nandrolone decanoate (nonload, steroid, n = 18),
      loading (load, nonsteroid, n = 18), or both (load, steroid, n = 18). A control
      group received no treatment (nonload, nonsteroid [NLNS], n = 18). Bioartificial
      tendons' remodeling was assessed by daily scanning, cytoskeletal organization by
      staining, matrix metalloproteinase-3 levels by ELISA assay, and biomechanical
      properties by load-to-failure testing. RESULTS: The load, steroid group showed
      the greatest remodeling and the best organized actin cytoskeleton. Matrix metallo
      proteinase-3 levels in the load, steroid group were greater than those of the
      nonload, nonsteroid group (P <.05). Ultimate stress and ultimate strain in the
      load, steroid group were greater than those of the nonload, nonsteroid and
      nonload, steroid groups (P <.05). The strain energy density in the load, steroid
      group was greater when compared to other groups (P <.05). CONCLUSIONS: Nandrolone
      decanoate and load acted synergistically to increase matrix remodeling and
      biomechanical properties of bioartificial tendons. CLINICAL RELEVANCE: Data
      suggest anabolic steroids may enhance production of bioartificial tendons and
      rotator cuff tendon healing in vitro. More research is necessary before such
      clinical use is recommended.

PMID- 15150041
TI  - Endoscopic evaluation and treatment of groin pain in the athlete.
AB  - BACKGROUND: Chronic groin pain in athletes forms a major diagnostic and
      therapeutic challenge. HYPOTHESIS: Evaluate and treat undiagnosed groin pain in
      the athlete by endoscopy. STUDY DESIGN: Prospective cohort study. METHODS:
      Athletes who were referred to the Ikazia Hospital with undiagnosed chronic groin
      pain between January 1998 and August 2001 were included. Radiography, bone
      scintigraphy, and ultrasonography were performed. In 14 athletes, groin pain
      remained undiagnosed. Ten patients complained of unilateral, 4 of bilateral groin
      pain. Patients underwent a transabdominal or extraperitoneal diagnostic
      endoscopy. RESULTS: All patients were operated ambulatory without significant
      difficulties. Pathology found by endoscopy was hernia inguinalis (n = 9), hernia
      femoralis (n = 4), preperitoneal lipoma (n = 3), and hernia obturatoria (n = 1).
      Only once was there no pathology. In 17 groins, a Prolene mesh was placed
      preperitoneally. Thirteen patients (93%) returned to full activity within 3
      months of surgery. One year after surgery, one patient had minor symptoms and one
      patient had persistent symptoms. All other patients had no complaints.
      CONCLUSIONS: An occult hernia should be high on the list of differential
      diagnoses in undiagnosed chronic groin pain in athletes. Operative treatment can
      return the patient to his sport within 3 months.

PMID- 15150042
TI  - A biomechanical evaluation of transcondylar femoral fixation of anterior cruciate
      ligament grafts.
AB  - BACKGROUND: Interference screw fixation of the graft in anterior cruciate
      ligament reconstruction is considered the gold standard, but limited clinical
      experience suggests that transcondylar fixation is equally effective. PURPOSE: To
      compare transcondylar and interference screw fixation. STUDY DESIGN: Ex vivo
      biomechanical study. METHODS: Twenty pairs of unembalmed knees underwent anterior
      cruciate ligament reconstruction with patellar tendon autografts. In 1 knee of
      each pair, the bone plug was stabilized in the femoral tunnel with standard
      interference screws; in the other knee, transcondylar screws were used. Testing
      to failure occurred immediately or after 1000 cycles of sinusoidal loading (30 to
      150 N) (20 paired reconstructions each). Fixation stiffness, strength, graft
      creep, displacement amplitude, and change in amplitude were measured and compared
      (repeated measures anaylsis of variance with Tukey test; P <.05). RESULTS: There
      was no significant difference in acute strength, maximum load within 3 mm, or
      stiffness between transcondylar fixation (410 +/- 164 N, 183 +/- 93 N, and 49.6
      +/- 28 N/mm, respectively) and interference fixation (497 +/- 216 N, 206 +/- 115
      N, and 61 +/- 37.8 N/mm, respectively). Similarly, there was no significant
      difference in cyclic strength, maximum load within 3 mm, or stiffness between
      transcondylar fixation (496 +/- 214 N, 357 +/- 82.9 N, and 110 +/- 27.4 N/mm,
      respectively) and interference fixation (552 +/- 233 N, 357 +/- 76.2 N, and 112
      +/- 26.8 N/mm, respectively). Predominant modes of failure were bone plug pullout
      (transcondylar fixation) and tendon failure or bone plug fracture (interference
      fixation). CONCLUSIONS: Transcondylar screw fixation of the patellar tendon
      autograft into the femoral tunnel performed mechanically as well as interference
      screw fixation. CLINICAL RELEVANCE: The results suggest that transcondylar and
      interference screws provide similar fixation for anterior cruciate ligament
      reconstruction.

PMID- 15150043
TI  - A biomechanical comparison of initial soft tissue tibial fixation devices: the
      Intrafix versus a tapered 35-mm bioabsorbable interference screw.
AB  - BACKGROUND: Biomechanical testing of the Intrafix device has not been performed
      using human tibiae. HYPOTHESIS: The Intrafix device would provide comparable or
      superior tibial fixation of a quadrupled hamstring tendon graft to a 35-mm-long
      bioabsorbable interference screw. STUDY DESIGN: In vitro, biomechanical study.
      METHODS: Eight paired human tibiae and 16 quadrupled hamstring tendon grafts were
      divided into 2 groups. Each quadrupled hamstring tendon graft was fixed in a
      tunnel sized to 0.5 mm graft diameter with either an Intrafix device or a screw.
      RESULTS: Displacement at failure was greater in the Intrafix group (17.3 +/- 4.6
      mm versus 10.9 +/- 4.4 mm, P =.002). Load at failure (796 +/- 193 N versus 647 +/
      269 N), stiffness (49.2 +/- 21.9 N/mm versus 64.5 +/- 22 N/mm), and bone mineral
      density (0.74 +/- 0.15 gm/cm(3) versus 0.74 +/- 0.14 gm/cm(3)) did not display
      significant differences for the Intrafix device and the screw, respectively (P
      >.05). CONCLUSIONS: Displacement at failure was greater for the Intrafix device.
      CLINICAL RELEVANCE: Increased displacement at failure for the Intrafix group
      suggests slippage from sheath channel deployment. Concentric fixation may not
      occur when less than optimal tibial bone mineral density increases the difficulty
      of attaining precise sheath deployment and quadrupled hamstring tendon graft
      strand alignment.

PMID- 15150044
TI  - Mobile superior glenoid labrum: a normal variant or pathologic condition?
AB  - BACKGROUND: Arthroscopic differentiation between a pathologic superior labrum
      anterior posterior lesion and a normal anatomic variant may be difficult.
      HYPOTHESIS: Various anatomic patterns exist that systematically characterize
      superior biceps-labral configurations. One variant involves a mobile superior
      labrum with exposed articular cartilage on the superior glenoid tubercle. The
      authors seek to demonstrate that this is nonpathologic. STUDY DESIGN: A
      prospective, consecutive descriptive anatomic study with 1-year clinical follow
      up of a subgroup with an identified mobile superior labrum. METHODS: A total of
      191 consecutive patients were prospectively evaluated arthroscopically to
      quantify the dimensions of the labrum and articular cartilage on the supraglenoid
      tubercle. RESULTS: A subgroup of 49 patients was identified with articular
      cartilage on the supraglenoid tubercle, a mobile labrum, and no fibrous tearing
      or evident injury in this region. In postoperative follow-up, only 1 (2.0%) of
      these patients was clinically symptomatic in the region of the superior labrum
      biceps origin. CONCLUSIONS: Indication for repair of a mobile superior glenoid
      labrum must be carefully addressed in the context of normal anatomic morphologic
      variability. The labral and supraglenoid tubercle morphology was noted to be
      highly variable. CLINICAL RELEVANCE: Patients with mobile labral tissue overlying
      intact articular cartilage, and no evidence of trauma, are not candidates for
      repair.

PMID- 15150045
TI  - Contact pressure at osteochondral donor sites in the patellofemoral joint.
AB  - BACKGROUND: The lowest contact pressure point is presumed to be the best site to
      harvest an osteochondral plug and minimize morbidity. HYPOTHESIS: Patellofemoral
      contact pressures are not uniform and are lowest along the medial patellofemoral
      articulation. STUDY DESIGN: Controlled laboratory study. METHODS: Seven cadaveric
      knees were tested with an electroresistive, dynamic pressure sensor placed onto
      the femoral side of the patellofemoral joint. The extensor mechanism was loaded
      with 89.1 N and 178.2 N, and the knee was manually cycled 3 times (0 degrees -105
      degrees ) per load. Mean trochlear pressures were calculated. RESULTS: Mean
      contact pressures were greatest in the central trochlea (5.80 kgf/cm(2)),
      followed by the lateral (2.56 kgf/cm(2)) and medial trochlea (1.60 kgf/cm(2)) at
      89.1 N (P <.05). At 178.2 N, pressures increased to 9.47, 5.81, and 2.75
      kgf/cm(2), respectively (P <.05). Lateral trochlear pressures decreased moving
      distally from 1.25 to 0.50 kgf/cm(2) at 89.1 N and 4.57 to 1.29 kgf/cm(2) at
      178.2 N. CONCLUSIONS: Contact pressures are lowest along the medial trochlea and
      decrease distally along the lateral trochlea. CLINICAL RELEVANCE: Osteochondral
      plugs from the medial femoral trochlea may be desirable if trochlear size
      permits. If harvesting from the lateral femoral trochlea, consider harvesting
      distally near the sulcus terminalis.

PMID- 15150046
TI  - Abnormal rotational knee motion during running after anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: The effectiveness of anterior cruciate ligament reconstruction for
      restoring normal knee kinematics is largely unknown, particularly during sports
      movements generating large, rapidly applied forces. HYPOTHESIS: Under dynamic in
      vivo loading, significant differences in 3-dimensional kinematics exist between
      anterior cruciate ligament-reconstructed knees and the contralateral, uninjured
      knees. STUDY DESIGN: Prospective, in vivo laboratory study. METHODS: Kinematics
      of anterior cruciate ligament-reconstructed and contralateral (uninjured) knees
      were evaluated for 6 subjects during downhill running 4 to 12 months after
      anterior cruciate ligament reconstruction, using a 250 frame/s stereoradiographic
      system. Anatomical reference axes were determined from computed tomography scans.
      Kinematic differences between the uninjured and reconstructed limbs were
      evaluated with a repeated-measures analysis of variance. RESULTS: Anterior tibial
      translation was similar for the reconstructed and uninjured limbs. However,
      reconstructed knees were more externally rotated on average by 3.8 +/- 2.3
      degrees across all subjects and time points (P =.0011). Reconstructed knees were
      also more adducted, by an average of 2.8 +/- 1.6 degrees (P =.0091). Although
      differences were small, they were consistent in all subjects. CONCLUSIONS:
      Anterior cruciate ligament reconstruction failed to restore normal rotational
      knee kinematics during dynamic loading. CLINICAL RELEVANCE: Although further
      study is required, these abnormal motions may contribute to long-term joint
      degeneration associated with anterior cruciate ligament injury/reconstruction.

PMID- 15150047
TI  - Tibiofemoral kinematics following successful anterior cruciate ligament
      reconstruction using dynamic multiple resonance imaging.
AB  - BACKGROUND: The aim of anterior cruciate ligament reconstruction is to reduce
      excess joint laxity, hoping to restore normal tibiofemoral kinematics and
      therefore improve joint stability. It remains unclear if successful ACL
      reconstruction restores normal tibiofemoral kinematics and whether it is this
      that is associated with a good result. STUDY: Case series. PURPOSE: To assess the
      kinematics of the anterior cruciate ligament-reconstructed knee using open-access
      MRI. METHODS: Tibiofemoral motion was assessed using open-access MRI,
      weightbearing through the arc of flexion from 0 degrees to 90 degrees in 10
      patients with isolated reconstruction of the anterior cruciate ligament
      (hamstring autograft) in one knee and a normal contralateral knee. Midmedial and
      midlateral sagittal images were analyzed in all positions of flexion in both
      knees to assess the tibiofemoral relationship. Sagittal laxity was also assessed
      by performing the Lachman test while the knees were scanned dynamically using
      open-access MRI. RESULTS: The amount of excursion between the tibial and femoral
      joint surfaces was similar between the normal and reconstructed knees, but the
      relationship of tibia to femur was always different for each position of knee
      flexion assessed-the lateral tibia being about 5 mm more anterior in the anterior
      cruciate ligament-reconstructed knees. This anterior tibial position is
      statistically significantly different at 0 degrees (P <.0006), 20 degrees (P
      =.0004), 45 degrees (P =.002), and 90 degrees of flexion (P <.006).
      Anteroposterior laxity was similar between normal and anterior cruciate ligament
      reconstructed knees. CONCLUSION: Anterior cruciate ligament reconstruction
      reduces sagittal laxity to within normal limits but does not restore normal
      tibiofemoral kinematics despite a successful outcome.

PMID- 15150048
TI  - The effect of length on the structural properties of an Achilles tendon graft as
      used in posterior cruciate ligament reconstruction.
AB  - BACKGROUND: The clinical outcomes of posterior cruciate ligament reconstruction
      are varied. No previous studies have investigated the effect of graft length on
      the structural properties of the graft. HYPOTHESIS: Graft length significantly
      affects the structural properties of posterior cruciate ligament grafts. STUDY
      DESIGN: Controlled laboratory study. METHODS: Eight Achilles tendon grafts were
      tested under tensile loads up to 400 N at 3 different lengths: long (75 mm),
      medium (48 mm), and short (34 mm). These 3 lengths represent midtunnel fixation,
      inlay fixation, and fixation near the ligament insertions. RESULTS: Shortening
      the graft from both long to medium and from medium to short increased the
      stiffness by approximately 25%. Long and medium grafts displaced significantly
      more than medium and short grafts, respectively. CONCLUSION: The effective length
      of a graft, which is determined by where it is fixed, should be considered an
      important variable in posterior cruciate ligament reconstruction.

PMID- 15150049
TI  - Surgical correction of internal coxa saltans: a 20-year consecutive study.
AB  - PURPOSE: To report the complications associated with surgical correction of
      internal snapping hip. STUDY DESIGN: Retrospective review. METHODS: A review of
      92 cases of internal coxa saltans (12 bilateral) from 1982 to 2002 was performed
      to identify complications following primary surgical correction. An inguinal
      approach was used for iliopsoas tendon fractional lengthening. The average follow
      up time per patient was 5.4 years. RESULTS: A total of 40 complications occurred
      in 32 patients. Complications included persistent hip pain (n = 6), sensory
      deficit (n = 8), and hip flexor weakness persisting longer than 1 month (n = 3).
      Additionally, painful bursa formation (n = 1), hematoma requiring reexploration
      (n = 1), and superficial infection (n = 1) were noted. Some patients developed
      recurrent snapping after a 3-month snapping-free interval (n = 9), and some
      patients never had complete resolution of snapping and were considered failures
      (n = 11). Of these failures/recurrences, 8 patients had a second tenotomy with 4
      failures. Two had a third tenotomy, with 1 failure. CONCLUSIONS: In this series,
      primary iliopsoas tendon lengthening in patients with internal coxa saltans was
      without any complication in only 60% of patients; however, overall patient
      satisfaction was 89%.

PMID- 15150050
TI  - Injury mechanisms for anterior cruciate ligament injuries in team handball: a
      systematic video analysis.
AB  - OBJECTIVE: To describe the mechanisms for anterior cruciate ligament injuries in
      female team handball. STUDY DESIGN: Descriptive video analysis. METHODS: Twenty
      videotapes of anterior cruciate ligament injuries from Norwegian or international
      competition were collected from 12 seasons (1988-2000). Three medical doctors and
      3 national team coaches systematically analyzed these videos to describe the
      injury mechanisms and playing situations. In addition, 32 anterior cruciate
      ligament-injured players in the 3 upper divisions in Norwegian team handball were
      interviewed during the 1998-1999 season to compare the injury characteristics
      between player recall and the video analysis. RESULTS: Two main injury mechanisms
      for anterior cruciate ligament injuries in team handball were identified. The
      most common (12 of 20 injuries), a plant-and-cut movement, occurred in every case
      with a forceful valgus and external or internal rotation with the knee close to
      full extension. The other main injury mechanism (4 of 20 injuries), a 1-legged
      jump shot landing, occurred with a forceful valgus and external rotation with the
      knee close to full extension. The results from the video analysis and
      questionnaire data were similar. CONCLUSIONS: The injury mechanism for anterior
      cruciate ligament injuries in female team handball appeared to be a forceful
      valgus collapse with the knee close to full extension combined with external or
      internal rotation of the tibia.

PMID- 15150051
TI  - Reflexive muscle activation alterations in shoulders with anterior glenohumeral
      instability.
AB  - BACKGROUND: Patients with glenohumeral instability have proprioceptive deficits
      that are suggested to contribute to muscle activation alterations. HYPOTHESIS:
      Muscle activation alterations will be present in shoulders with anterior
      glenohumeral instability. STUDY DESIGN: Posttest-only control group design.
      METHODS: Eleven patients diagnosed with anterior glenohumeral instability were
      matched with 11 control subjects. Each subject received an external humeral
      rotation apprehension perturbation while reflexive muscle activation
      characteristics were measured with indwelling electromyography and surface
      electromyography. RESULTS: Patients with instability demonstrated suppressed
      pectoralis major and biceps brachii mean activation; increased peak activation of
      the subscapularis, supraspinatus, and infraspinatus; and a significantly slower
      biceps brachii reflex latency. Supraspinatus-subscapularis coactivation was
      significantly suppressed in the patients with instability as well. CONCLUSIONS
      AND CLINICAL RELEVANCE: In addition to the capsuloligamentous deficiency and
      proprioceptive deficits present in anterior glenohumeral instability, muscle
      activation alterations are also present. The suppressed rotator cuff
      coactivation, slower biceps brachii activation, and decreased pectoralis major
      and biceps brachii mean activation may contribute to the recurrent instability
      episodes seen in this patient group. Clinicians can implement therapeutic
      exercises that address the suppressed muscles in patients opting for conservative
      management or rehabilitation before and after capsulorraphy procedures.

PMID- 15150052
TI  - Proximal tibiofibular joint ganglion cysts: excision, recurrence, and joint
      arthrodesis.
AB  - OBJECTIVE: Proximal tibiofibular joint proximal tibiofibular joint cysts are rare
      entities that can cause disability. Excision remains the traditional surgical
      treatment. Cyst recurrence has been a problem. This study reviews one of the
      largest series of patients with proximal tibiofibular joint cysts and evaluates
      the role of a new surgical option, proximal tibiofibular joint fusion. METHODS:
      Thirteen patients were admitted to the institution between 1987 and 1999.
      Diagnoses were confirmed by magnetic resonance imaging and histological
      examination. A database was compiled after medical record review. Patients
      completed a phone survey describing activity levels, symptom severity, recurrence
      history, and additional surgery. Average postoperative follow-up and average time
      to date of survey were 1.7 and 6.3 years, respectively. RESULTS: Patient
      complaints included lateral knee "fullness" (75%) and peroneal nerve dysesthesias
      (54%). Twelve patients opted for surgery: cyst excision (8) and cyst excision
      with proximal tibiofibular joint fusion (4). A recurrence rate of 13% (1 of 8)
      following primary excision was observed. A 100% (3 of 3) repeat recurrence rate
      was noted in second resections. Four patients underwent proximal tibiofibular
      joint fusion: 2 with a recurrence history and 2 for primary treatment. At follow
      up, all fusion patients were without cyst recurrence or activity limitations.
      Procedure morbidity was minimal. CONCLUSIONS: Proximal tibiofibular joint cysts
      can recur after simple excision. Repeat resection after a recurrence is often not
      effective. Proximal tibiofibular joint arthrodesis appears to be a more effective
      surgical option after a recurrence.

PMID- 15150053
TI  - A simple, accurate method to confirm placement of intra-articular knee injection.
AB  - BACKGROUND: Intra-articular knee injections are routinely performed in clinical
      practice without documenting intra-articular placement. HYPOTHESIS: A small
      amount of air to an intra-articular knee injection produces an audible
      "squishing" sound with range of motion. STUDY DESIGN: Prospective nonrandomized
      clinical trial. METHODS: The study group (20 knees from 20 patients) received an
      intra-articular injection with a mixture of local anesthetic, corticosteroid,
      contrast dye, and 1 to 2 cc of air. The control group (10 knees from 5 patients)
      received extra-articular injections of a mixture of local anesthetic, contrast
      dye, and 2 cc of air. All knees were examined immediately after injection for a
      squishing sound with range of motion. Postinjection arthrographic radiographs
      were taken to verify the actual placement. RESULT: All study group knees and no
      control group knees had intra-articular contrast by radiograph. Clearly audible
      squishing sounds were heard in 17 of 20 study knees (sensitivity of 85%).
      Squishing sounds were audible in none of the control knees (specificity of 100%).
      CONCLUSION: Adding 1 to 2 cc of air to knee injections provides a no-cost,
      reliable, sensitive, and specific method of confirming accurate placement.
      CLINICAL RELEVANCE: This simple method is easily reproduced, can confirm accurate
      placement, and can eliminate extra-articular injection as the reason for clinical
      response failure.

PMID- 15150054
TI  - Relationship between stress fractures of the proximal phalanx of the great toe
      and hallux valgus.
AB  - PURPOSE: To clarify the relationship between stress fractures of the great toe
      and hallux valgus. METHODS: Ten cases of this fracture were analyzed for their
      alignment of the great toe. RESULTS: Nine of them had hallux valgus. DISCUSSION:
      The continuous bowstring effect of the extensor hallux longus and shearing stress
      on the hallux valgus that occur during specific exercises such as sprinting,
      jumping, and standing on tiptoe, could cause these stress fractures. CONCLUSION:
      The hallux valgus could play a role in the cause of stress fractures of the
      proximal phalanx of the great toe.

PMID- 15150055
TI  - The anterior meniscofemoral ligament of the medial meniscus: case series.

PMID- 15150056
TI  - Delayed fracture of the tibia following anteromedialization osteotomy of the
      tibial tubercle: a report of 5 cases.

PMID- 15150057
TI  - Traumatic pseudoaneurysm of the brachial artery caused by an osteochondroma,
      mimicking biceps rupture in a weightlifter: a case report.

PMID- 15150058
TI  - Cervical spinal cord injury in sumo wrestling: a case report.

PMID- 15150059
TI  - Acute peroneal compartment syndrome following ankle inversion injury: a case
      report.

PMID- 15150060
TI  - Nerve injury about the shoulder in athletes, part 2: long thoracic nerve, spinal
      accessory nerve, burners/stingers, thoracic outlet syndrome.
AB  - Nerve injuries about the shoulder in athletes are being recognized with
      increasing frequency. Prompt and correct diagnosis of these injuries is important
      to treat the patient and to understand the potential complications and natural
      history, so as to counsel our athletes appropriately. This 2-part article is a
      review and an overview of the current state of knowledge regarding some of the
      more common nerve injuries seen about the shoulder in athletes, including long
      thoracic nerve, spinal accessory nerve, burners and stingers, and thoracic outlet
      syndrome. Each of these clinical entities will be discussed independently,
      reviewing the anatomy, mechanism of injury, patient presentation (history and
      examination), the role of additional diagnostic studies, differential diagnosis,
      and management.

PMID- 15150061
TI  - Catastrophic cervical spine injuries in the collision sport athlete, part 1:
      epidemiology, functional anatomy, and diagnosis.
AB  - Catastrophic cervical spine injuries can lead to devastating consequences for the
      collision athlete. Improved understanding of these injuries can facilitate early
      diagnosis and effective on-field management. This article is the first of a 2
      part series. The first part reviews the current concepts regarding the
      epidemiology, functional anatomy, and diagnostic considerations relevant to
      cervical spine trauma in collision sports. In the second part, to be published
      later, the principles of emergency care of the cervical spine-injured athlete are
      reviewed. This article provides a rational approach to the early recognition of
      the different clinical syndromes associated with catastrophic cervical spine
      injury. Rapid on-field diagnosis can help to optimize the outcomes of these
      catastrophic injuries.

PMID- 15150062
TI  - DNA fingerprinting and breast cancer.

PMID- 15150063
TI  - DNA fingerprints provide a patient-specific breast cancer marker.
AB  - BACKGROUND: Detection of systemic breast cancer recurrence is limited by lack of
      universally expressed tumor cell markers. We hypothesized that a test that
      detects genetic alterations specific to breast cancer cells of an individual
      patient would provide a superior cancer marker. METHODS: DNA was extracted from
      blood, primary tumor, and axillary lymph nodes of 33 breast cancer patients and
      normal breast tissue of 12 control patients. A patient's genome was scanned by
      PCR amplification between Alu sequences. A DNA fingerprint of approximately 17-40
      bands was produced for comparison between normal blood and sampled tissues.
      RESULTS: There were 7 stage I, 18 stage II, 7 stage III, and 1 stage IV breast
      cancer cases; 33 of 33 cancer cases showed DNA fingerprint differences between
      blood and primary tumor (P <.0001). This test predicted 100% of positive nodes.
      No false-negatives occurred, and in two cases malignancy was detected in
      histologically negative nodes. Three of the 12 controls showed a single similar
      band change. CONCLUSIONS: DNA fingerprinting is a method for detecting and
      characterizing genetic alterations specific to an individual patient's primary
      tumor in 100% of cases tested. These specific changes were also identified in
      100% of positive nodes, proving the capacity of the test to detect metastases.

PMID- 15150064
TI  - Pancreatic duct strictures: identifying risk of malignancy.
AB  - BACKGROUND: This study aimed to define PDS characteristics that predict
      malignancy and would thus invoke further diagnostic evaluation or aggressive
      treatment. METHODS: 355 cases of PDS were diagnosed by ERCP during a 7-year
      period at a single institution. A retrospective review identified
      clinical/demographic patient data and ERCP results. RESULTS: 218 (61%) patients
      with a PDS were found to have an isolated PDS. Twelve percent of isolated PDS and
      79% of CBD stricture-associated PDS were malignant. The sensitivity and
      specificity for the double duct sign for malignancy were 77% and 80%
      respectively, and the positive predictive value was 65%. Predictors of malignancy
      were statistically similar for both isolated PDS and those associated with a CBD
      stricture. Univariate predictors of malignancy included stricture location in the
      pancreatic head/neck, jaundice, and patient age. Predictors of benign disease
      included a history of pancreatitis, the presence of multiple strictures,
      pancreatic duct stones, pseudocyst, pancreas divisum anatomy, irregular side
      branches, and irregular pancreatic duct morphology. Less than 1% of patients with
      either pancreas divisum anatomy, pancreatic duct stones, or pancreatic pseudocyst
      had malignancy. Using malignancy as the dependent variable, multivariate factors
      included in the final prognostic equation were history of pancreatitis (odds
      ratio 0.009 with history of pancreatitis), stricture location in the head or neck
      (odds ratio 42) and irregular pancreatic duct side branches (odds ratio 0.05 with
      irregular branches). CONCLUSIONS: This study demonstrates that certain
      characteristics of PDS can predict the subset of patients who have an increased
      risk of cancer.

PMID- 15150065
TI  - ERCP and pancreatic cancer.

PMID- 15150066
TI  - How many breast cancer cells in a sentinel lymph node are OK?

PMID- 15150067
TI  - Laparoscopic placement of hepatic arterial pumps: a true advance or a lot of
      effort for a procedure with a diminishing role?

PMID- 15150068
TI  - Laparoscopic placement of hepatic artery infusion pumps: technical considerations
      and early results.
AB  - BACKGROUND: Laparoscopic hepatic artery infusion pump (LHAIP) placement is a
      novel treatment option for patients with colorectal liver metastases. This study
      investigates technical difficulties with regard to variant hepatic arteries and
      the preliminary outcomes for patients treated with LHAIP placement. METHODS:
      Between March 1998 and January 2003, 38 patients with colorectal metastases
      confined to the liver, 35 (92%) of who had prior systemic chemotherapy that
      failed, were treated with LHAIP. RESULTS: Twelve patients (32%) had LHAIP
      placement only, and 26 (68%) had pump placement combined with laparoscopic
      radiofrequency ablation (LRFA; 24 patients) and/or liver resection (2 patients).
      Variant hepatic arterial (HA) anatomy was present in 18 patients (47%). The
      presence of a variant HA did not increase pump complications, operative time, or
      blood loss (P >/=.20) or decrease the functional time of pump use (P =.91) in
      comparison with normal anatomy. In all patients with a variant HA, laparoscopic
      ligation of the variant vessel and/or cannulation of nongastroduodenal artery
      resulted in complete hepatic perfusion. Three misperfusions identified
      intraoperatively with use of methylene blue injection were corrected by
      laparoscopic ligation (two) or postoperative angioembolization (one).
      Postoperative pump radionuclide flow studies confirmed isolated hepatic artery
      infusion in all cases. There was a 13% pump-related complication rate. During a
      median follow-up of 11 months (0.5 to 35.5 months), the actuarial rate of overall
      survival was 47% and the estimated median survival time was 17.5 months.
      CONCLUSIONS: LHAIP placement is technically feasible, and variant HA is not
      associated with increased pump complications or decreased pump functional time.

PMID- 15150069
TI  - Prognostic factors in resected pathologic (p-) stage IIIA-N2, non-small-cell lung
      cancer.
AB  - BACKGROUND: Postoperative prognosis for patients with pathologic (p-) stage IIIA
      N2 non-small-cell lung cancer (NSCLC) is poor, and significant factors that
      influence the prognosis remain unclear. METHODS: A total of 99 patients who
      underwent complete resection for p-stage IIIA-N2 NSCLC without any preoperative
      therapy were retrospectively reviewed. Biological features such as tumor
      angiogenesis (intratumoral microvessel density [IMVD]), proliferative activity
      (proliferative index [PI]), and p53 status were also evaluated
      immunohistochemically. RESULTS: Univariate analysis revealed that the number of
      involved N2 stations was a significant prognostic factor; 5-year survival rates
      for a tumor with metastases in single N2 stations, tumor with metastases in two
      N2 stations, and tumor with metastases in 3 or more N2 stations were 41.6%,
      35.3%, and 0.0%, respectively (P =.041) In addition, the 5-year survival rate for
      cN0-1 disease was significantly higher than that for cN2 disease (41.9% and
      25.5%, respectively; P =.048) Tumor angiogenesis and proliferative activity were
      the most significant prognostic factors; 5-year survival rates for lower-IMDV
      tumor and higher-IMVD tumor were 53.6% and 15.9%, respectively (P =.002), and
      those for lower-PI tumor and higher-PI tumor were 47.0% and 20.4%, respectively
      (P =.019) There was no difference in the postoperative survival between tumor
      showing aberrant p53 expression and tumor showing no aberrant p53 expression.
      These results were confirmed by a multivariate analysis. CONCLUSIONS: P-stage
      IIIA-N2 NSCLC cases represented a mixture of heterogeneous prognostic subgroups,
      and the number of involved N2 stations, cN status, PI, and IMVD were significant
      predictors of the survival.

PMID- 15150070
TI  - Gastric cancer: establishing predictors of biologic behavior with use of
      population-based data.
AB  - BACKGROUND: Tumor thickness and nodal status are important predictors of survival
      following curative resection for gastric cancer. Lymphovascular invasion (LVI) is
      a potential predictor of biological behavior. The relationship between LVI and
      tumor thickness (T status) has not been established in population-based studies.
      METHODS: Clinicopathological and survival data of 577 patients at nine centers,
      from between 1991 and 1997, was collected from patient records and a Provincial
      Cancer Registry. The primary endpoint of the study was death. A secondary
      analysis of a node-negative subgroup examined the significance of LVI with
      respect to T status. RESULTS: The population disease-specific survival was 28%.
      In a multivariate analysis, T, N, M, esophageal margin, tumor morphology, and
      residual tumor category were independent predictors of survival. LVI was
      documented in 58% of resected tumors. LVI correlated with advancing T and N
      status but was not significant in a multivariate population model. Subgroup
      analysis of node-negative gastric cancer found T status and LVI to be independent
      predictors of survival. LVI was associated with a 5-year survival of 8%, versus
      43% among patients in whom it was absent (P <.001). CONCLUSIONS: T status and N
      status were the most important independent predictors of survival in a population
      based study of gastric cancer. LVI correlated with advancing N and T status.
      Multivariate analysis of node-negative patients showed LVI and T status are
      independent predictors of survival.

PMID- 15150071
TI  - Occult micrometastases in axillary lymph nodes predict subsequent distant
      metastases in stage I breast cancer: a case-control study with 15-year follow-up.
AB  - BACKGROUND: The prognostic significance of occult axillary metastases was
      evaluated in patients with stage I breast cancer. METHODS: Ninety-six patients
      with pT1 breast carcinoma who underwent axillary lymph node dissection had
      negative nodes in routine microscopic examination. Forty-eight patients developed
      distant metastases within 15 years after surgery (M group) and are compared to 48
      age-matched patients who were disease-free for 15 years (NM group). We reexamined
      1539 lymph nodes from these patients, using three levels and cytokeratin
      immunostain. RESULTS: Occult metastases were detected in 21 patients: 16 of 48
      (34%) in the M group and 5 of 48 (11%) in the NM group (P =.007). All metastases
      measured 2.0 mm or less and were classified as micrometastases (>0.2 mm to 2.0
      mm) in 11 cases and as individual tumor cells (individual cells or clusters
      measuring < or =0.2 mm) in 10 cases. Micrometastases were 10 times more frequent
      in the M group than in the NM group (10/48 vs. 1/48; P =.004). Although there was
      no difference in tumor size, histologic type, estrogen receptor status, or type
      of treatment between the two patient groups, tumors in the M group were of a
      higher grade, had higher mitotic index and showed lymphovascular invasion. In
      multiple logistic regression, only high mitotic index and presence of
      micrometastases showed an independent significant correlation with the subsequent
      occurrence of distant metastases. CONCLUSIONS: The presence of micrometastases
      (>0.2 to 2.0 mm) in axillary nodes is significantly associated with the
      development of distant metastases in patients with T1 breast cancer.

PMID- 15150073
TI  - Critical stages in the recruitment process of Rhamnus alaternus L.
AB  - BACKGROUND AND AIMS: Rhamnus alaternus is a Mediterranean shrub commonly used in
      reforestation programs. Although several aspects of its reproductive biology have
      been studied, little is known about the importance of the different recruitment
      stages in the overall regeneration process of this species, which limits its
      proper use in Mediterranean forests and shrubland management. The aim of the
      present work was to quantify the importance of the different recruitment stages
      in the regeneration process of R. alaternus. METHODS: Two populations of Rhamnus
      alaternus on the island of Mallorca that differ in climatic conditions, type of
      habitat and sex ratio were studied. The importance of seed production, seed
      dispersal and predation, seedling emergence and seedling survival for the
      regeneration of this species were quantified. KEY RESULTS: In both populations,
      fruit set and fruit removal by animals were not critical stages, since almost
      half of the flowers became mature fruits and 90% of those were dispersed. Most
      seeds were deposited under female conspecifics (86 and 47%, at Lloret and
      Esporles, respectively), and very few were found in open inter-spaces (1 and 5%).
      Post-dispersal seed predation (mostly by ants and rodents) was very high in both
      populations. Seedling emergence took place during autumn and early winter and it
      ranged from 31 to 68% depending upon year and microhabitat. The majority of
      emerged seedlings died during the first year, mainly due to desiccation; such
      mortality was influenced by rainfall and differed among microhabitats (varying
      from 67 to 100%). The general spatial distribution of seed rain was concordant
      with the seedling emergence and survival pattern in both populations.
      CONCLUSIONS: The recruitment of Rhamnus alaternus appeared to be mainly limited
      by seed and seedling survival, regardless of the type of habitat in which the
      species is found.

PMID- 15150072
TI  - Ecophysiology of Crassulacean Acid Metabolism (CAM).
AB  - BACKGROUND AND SCOPE: Crassulacean Acid Metabolism (CAM) as an ecophysiological
      modification of photosynthetic carbon acquisition has been reviewed extensively
      before. Cell biology, enzymology and the flow of carbon along various pathways
      and through various cellular compartments have been well documented and
      discussed. The present attempt at reviewing CAM once again tries to use a
      different approach, considering a wide range of inputs, receivers and outputs.
      INPUT: Input is given by a network of environmental parameters. Six major ones,
      CO(2), H(2)O, light, temperature, nutrients and salinity, are considered in
      detail, which allows discussion of the effects of these factors, and combinations
      thereof, at the individual plant level ('physiological aut-ecology'). RECEIVERS:
      Receivers of the environmental cues are the plant types genotypes and phenotypes,
      the latter including morphotypes and physiotypes. CAM genotypes largely remain
      'black boxes', and research endeavours of genomics, producing mutants and
      following molecular phylogeny, are just beginning. There is no special
      development of CAM morphotypes except for a strong tendency for leaf or stem
      succulence with large cells with big vacuoles and often, but not always, special
      water storage tissues. Various CAM physiotypes with differing degrees of CAM
      expression are well characterized. OUTPUT: Output is the shaping of habitats,
      ecosystems and communities by CAM. A number of systems are briefly surveyed,
      namely aquatic systems, deserts, salinas, savannas, restingas, various types of
      forests, inselbergs and paramos. CONCLUSIONS: While quantitative census data for
      CAM diversity and biomass are largely missing, intuition suggests that the larger
      CAM domains are those systems which are governed by a network of interacting
      stress factors requiring versatile responses and not systems where a single
      stress factor strongly prevails. CAM is noted to be a strategy for variable,
      flexible and plastic niche occupation rather than lush productivity.
      'Physiological syn-ecology' reveals that phenotypic plasticity constitutes the
      ecophysiological advantage of CAM.

PMID- 15150074
TI  - Histone H1-like protein participates in endothelial cell-specific activation of
      the von Willebrand factor promoter.
AB  - A region of the von Willebrand factor (VWF) promoter has been identified that is
      necessary to confer endothelial cell-specific activation to the VWF promoter.
      This region spans sequences +155 to +247 and contains binding sites for GATA6 and
      NFY transcription factors. To identify potential DNA binding transcription
      factors that directly interact with these sequences in an endothelial-specific
      manner, we have performed extensive gel mobility assays with use of 7 overlapping
      DNA probes that collectively span this entire region. An endothelial-specific
      protein DNA complex was formed with an oligonucleotide that corresponded to
      sequences +155 to +184 of the VWF gene. Mutation analysis identified a 6
      nucleotide element corresponding to sequences +164 to +169 as the core-binding
      region for the formation of this complex. Transfection analysis demonstrated that
      the mutation, which abolished DNA-protein interaction, resulted in significant
      inhibition of the VWF promoter activity. DNA pull-down analysis, mass
      spectrometry, and Western blot analysis demonstrated that a 32-kDa polypeptide
      with homology to histone H1 constituted the endothelial-specific DNA binding
      protein, or a DNA binding subunit of this protein complex. On the basis of these
      results, we hypothesize that an H1-like protein functions as an endothelial cell
      specific transcriptional activator of the VWF promoter.

PMID- 15150075
TI  - Renal venous thrombosis in neonates: prothrombotic risk factors and long-term
      follow-up.
AB  - The present study was designed to evaluate prothrombotic risk profiles in 59
      consecutively recruited white neonates with renal venous thrombosis (RVT). The
      rates of prothrombotic risk factors (PRs)-for example, the factor V (FV) 1691G> A
      mutation, the factor II (FII) 20210G> A variant, antithrombin (AT), protein C
      (PC), protein S (PS), elevated lipoprotein(a) (Lp(a)), total fasting plasma
      homocysteine (tHcy) levels, and anticardiolipin antibodies (ACAs)-were compared
      with those of 118 healthy control children. At onset, 32 (54.2%) of the 59
      neonates showed underlying clinical conditions; 40 (67.8%) of them and 23 (85.2%)
      of the 27 infants with idiopathic RVT showed at least one PR. Univariate analysis
      revealed significantly elevated odds ratios/95% confidence intervals (ORs/95%
      CIs) for FV and Lp(a). Additionally, PC/AT deficiency and ACAs were found
      significantly more often in the patient group (P =.04). Multivariate analysis
      calculated significant ORs/95% CIs only for FV (OR, 9.4; 95% CI, 3.3-26.6) and
      elevated Lp(a) (OR, 7.6; 95% CI, 2.4-23.8). Of the 59 neonates investigated, 53
      revealed renal atrophy, and 13 children additionally suffered from severe
      arterial hypertension. In conclusion, the present study demonstrates the
      significance of genetic PR-especially the FV mutation and elevated Lp(a)-for the
      etiology of neonatal RVT.

PMID- 15150077
TI  - Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an
      animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host.
AB  - To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed
      hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P
      infected, immunosuppressed rhesus macaques with the EBV-related rhesus
      lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4
      immunocompetent animals was characterized by an acute viremia and seroconversion
      followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected
      orally with LCV failed to develop an LCV-specific humoral response and viremia
      was more pronounced, but there was no evidence of LCV-induced lymphoproliferative
      disease. A more aggressive primary challenge was administered by intravenous
      inoculation of 10(8) autologous, LCV-immortalized B cells in 4 additional
      immunosuppressed animals. Two animals with modest immunosuppression remained
      asymptomatic, and 1 of 2 severely immunosuppressed animals developed an
      aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the
      potential for lymphomagenesis in an experimental model system for EBV infection
      and underscore the strength and depth of immune control in limiting LCV-induced
      lymphoproliferative disease.

PMID- 15150076
TI  - Antineutrophil cytoplasmic autoantibodies against the murine homolog of
      proteinase 3 (Wegener autoantigen) are pathogenic in vivo.
AB  - Antineutrophil cytoplasmic autoantibodies (ANCAs) recognizing human proteinase 3
      of neutrophil granules are a diagnostic hallmark of Wegener granulomatosis, an
      autoimmune systemic vasculitis with predilection for the respiratory tract and
      kidneys. In vitro experiments have implicated several mechanisms by which ANCAs
      may lead to tissue injury. However, little is known about the pathogenic
      significance of proteinase 3-specific antibodies in vivo. In vivo models for ANCA
      mediated proinflammatory effects have not been forthcoming, primarily because
      ANCA epitopes on human proteinase 3 are not shared by the murine homolog. In this
      study we generated ANCAs against recombinant murine proteinase 3 in proteinase
      3/neutrophil elastase-deficient mice that recognized the murine antigen on the
      surface of neutrophils. Local inflammation induced by intradermal injection of
      tumor necrosis factor alpha triggered a stronger subcutaneous panniculitis in the
      presence of passively transferred systemic proteinase 3-ANCAs than in the
      presence of mock immune serum. When we transferred mouse proteinase 3-ANCA serum
      to systemically lipopolysaccharide-primed wild-type mice, mice treated with
      proteinase 3-ANCAs did not develop significantly stronger signs of inflammation
      of the lungs or kidneys than the respective mock immune serum-treated animals. In
      conclusion, our in vivo study provides the first evidence for a pathogenic effect
      of proteinase 3-specific ANCAs at local sites of inflammation.

PMID- 15150078
TI  - Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk
      factor for fetal death.
AB  - The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death
      but the pathologic mechanisms are poorly understood. Since endothelial protein C
      receptor (EPCR) plays a role in the anticoagulant system and in placental
      development, we hypothesized that anti-EPCR autoantibodies may be involved in
      clinical manifestations of APS and in fetal loss. The levels of immunoglobulin M
      (IgM) and IgG anti-EPCR autoantibodies were analyzed by enzyme-linked
      immunosorbent assay (ELISA) in 43 patients with APS and 43 controls. Anti-EPCR
      levels were higher in APS patients than in controls. Interestingly, one of the
      IgM anti-EPCR autoantibodies inhibited the generation of activated protein C on
      endothelium. Since markedly high anti-EPCR levels were found in women with fetal
      death, 87 patients with a first episode of unexplained fetal death were
      subsequently analyzed and their anti-EPCR levels were compared with 87 matched
      controls. We found that anti-EPCR autoantibodies constitute an independent risk
      factor for a first fetal death episode: the adjusted odds ratios (ORs) for anti
      EPCR autoantibodies above the 95th percentile were 23.0 (95% confidence interval
      [CI], 2.0-266.3) for IgM and 6.8 (95% CI, 1.2-38.4) for IgG. Anti-EPCR
      autoantibodies can be detected in APS patients and are independent risk factors
      for fetal death.

PMID- 15150079
TI  - Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody
      mediated clearance of the GPVI/FcRgamma-chain complex from the human platelet
      surface.
AB  - Platelet glycoprotein (GP) VI is a 62-kDa membrane glycoprotein that exists on
      both human and murine platelets in a noncovalent complex with the Fc receptor
      (FcR) gamma chain. The GPVI/FcRgamma-chain complex serves as the major activating
      receptor for collagen, as evidenced by observations that platelets genetically
      deficient in GPVI or the FcRgamma chain are highly refractory to collagen-induced
      platelet activation. Recently, several different rat anti-murine GPVI monoclonal
      antibodies, termed JAQs 1, 2, and 3, were produced that had the unique property
      of "immunodepleting" GPVI from the murine platelet surface and rendering it
      unresponsive to collagen or GPVI-specific agonists like convulxin or collagen
      related peptide (CRP). Herein, we describe a patient with a mild bleeding
      disorder and a moderately reduced platelet count whose platelets fail to become
      activated in response to collagen or CRP and inefficiently adhere to and form
      thrombi on immobilized collagen under conditions of arterial shear. Although the
      amount of GPVI platelet mRNA and the nucleotide sequence of the GPVI gene were
      found to be normal, both GPVI and the FcRgamma chain were nearly absent from the
      platelet surface and were markedly reduced in wholeplatelet detergent lysates.
      Patient plasma contained an autoantibody that bound specifically to GPVI
      positive, normal platelets, and cleared soluble GPVI from the plasma, suggesting
      that the patient suffers from a rare form of idiopathic thrombocytopenic purpura
      caused by a GPVI-specific autoantibody that mediates clearance of the
      GPVI/FcRgamma-chain complex from the platelet surface. Since antibody-induced
      GPVI shedding now has been demonstrated in both humans and mice, these studies
      may provide a rationale for developing therapeutic reagents that induce temporary
      depletion of GPVI for the treatment of clinical thrombosis.

PMID- 15150080
TI  - Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus
      host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is an increasingly common cause of
      morbidity and mortality in allogeneic stem cell transplantation (alloSCT).
      Relative to acute GVHD (aGVHD), much less is understood about cGVHD. Using the
      B10.D2 --> BALB/c murine cGVHD model, which shares critical pathologic features
      with human cGVHD, we find that radiation-resistant host T cells regulate cGVHD.
      We initially observed that recipients lacking all lymphocytes developed
      accelerated and more severe cGVHD. Using genetically deficient recipients, we
      determined that alphabeta+CD4+ T cells were required to regulate cGVHD. Increased
      cGVHD severity was not due to the absence of T cells per se. Rather, the potency
      of regulation was proportional to host T-cell receptor (TCR) diversity. Only
      CD4+CD25+, and not CD4+CD25-, host T cells ameliorated cGVHD when added back,
      indicating that host T cells acted not via host-versus-graft activity or by
      reducing homeostatic proliferation but by an undefined regulatory mechanism.
      Thus, preparative regimens that spare host CD4+CD25+ T cells may reduce cGVHD.
      Donor CD4+CD25+ T cells also reduced cGVHD. Depletion of CD4+CD25+ cells from the
      inoculum exacerbated disease, whereas transplantation of additional CD4+CD25+
      cells protected against severe cGVHD. Additional CD4+CD25+ cells also promoted
      healing of established lesions, suggesting that their effects persist during the
      evolution of cGVHD.

PMID- 15150081
TI  - Morbidity and mortality with nonmyeloablative compared with myeloablative
      conditioning before hematopoietic cell transplantation from HLA-matched related
      donors.
AB  - Nonmyeloablative regimens for allogeneic hematopoietic cell transplantation (HCT)
      have been developed for patients ineligible for myeloablative conditioning. We
      compared regimen-related toxicities (RRTs) and nonrelapse mortality (NRM) in 73
      nonmyeloablative and 73 myeloablative recipients of HLA-matched related donor
      HCT, using the National Cancer Institute (NCI) Common Toxicity Criteria.
      Nonmyeloablative regimens were 2 Gy total body irradiation (TBI), either alone (n
      = 40) or combined with fludarabine, 30 mg/m(2)/d for 3 days (n = 33).
      Posttransplantation immunosuppression included mycophenolate mofetil and
      cyclosporine. Myeloablative regimens consisted mostly of cyclophosphamide + TBI
      or busulfan + cyclophosphamide, followed by posttransplantation methotrexate and
      cyclosporine. Nonmyeloablative patients were at higher risk than ablative
      patients because of greater age, longer time from diagnosis to HCT, more frequent
      preceding high-dose HCT, and higher pretransplantation Charlson comorbidity
      scores. Nevertheless, they experienced significantly less severe toxicities in 7
      organs/systems: hematologic, gastrointestinal, hepatic, hemorrhage, infection,
      metabolic, and pulmonary. This translated into less NRM at day 100 (3% versus
      23%, P = 10(-4)) and 1 year (16% versus 30%, P =.04). In multivariate analysis,
      the strongest factor predicting lessened RRT and NRM was nonmyeloablative
      conditioning, whereas high pretransplantation comorbidity scores predicted higher
      NRM. In conclusion, nonmyeloablative regimens had lower RRT and NRM and could be
      considered for comparative studies, including younger patients with more
      favorable Charlson comorbidity scores.

PMID- 15150082
TI  - Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor
      activity: in vitro and in vivo assessment.
AB  - Aroylhydrazone and thiosemicarbazone iron (Fe) chelators have potent antitumor
      activity. The aim of the current study was to examine the antitumor effects and
      mechanisms of action of a novel series of Fe chelators, the di-2-pyridyl
      thiosemicarbazones. Of 7 new chelators synthesized, 4 showed pronounced
      antiproliferative effects. The most active chelator was Dp44mT, which had marked
      and selective antitumor activity-for example, an IC(50) of 0.03 microM in
      neuroepithelioma cells compared with more than 25 microM in mortal fibroblasts.
      Indeed, this antiproliferative activity was the greatest yet observed for an Fe
      chelator. Efficacy was greater than it was for the cytotoxic ligand 311 and
      comparable to that of the antitumor agent doxorubicin. Strikingly, Dp44mT
      significantly (P <.01) decreased tumor weight in mice to 47% of the weight in the
      control after only 5 days, whereas there was no marked change in animal weight or
      hematologic indices. Terminal deoxyribonucleotidyl transferase (TdT)-mediated
      dUTP nick end-labeling (TUNEL) staining demonstrated apoptosis in tumors taken
      from mice treated with Dp44mT. This chelator caused a marked increase of caspase
      3 activity in murine Madison-109 (M109) cells. Caspase activation was at least
      partially mediated by the release of mitochondrial holo-cytochrome c (h-cytc)
      after incubation with Dp44mT. In conclusion, Dp44mT is a novel, highly effective
      antitumor agent in vitro and in vivo that induces apoptosis.

PMID- 15150083
TI  - Transduction of NO-bioactivity by the red blood cell in sepsis: novel mechanisms
      of vasodilation during acute inflammatory disease.
AB  - Sepsis is an acute inflammatory disease characterized by dysfunctional blood flow
      and hypotension. Nitric oxide (NO) is elevated during sepsis and plays an
      integral role in the associated vascular pathology. However, precise mechanisms
      and functions of NO in sepsis remain unclear. In this study, we show that red
      blood cells (RBCs) are foci for nitrosative reactions during acute inflammation,
      resulting in the formation of cells that can promote systemic vascular relaxation
      in an uncontrolled manner. Specifically, using experimental models of endotoxemia
      and surgical sepsis, NO adducts were found in the RBCs, including S
      nitrosohemoglobin (SNOHb). These RBCs, referred to as septic RBCs, spontaneously
      stimulated vasodilation in a manner consistent with elevated SNOHb
      concentrations. Moreover, relaxation was cyclic guanosine monophosphate (cGMP)
      dependent and was inhibited by RBC lysis and glutathione but not by the NO
      scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C
      PTIO). The potential mechanism of septic RBC-mediated vasorelaxation is discussed
      and may involve the intermediate, nitroxyl (HNO). Coupled with data showing that
      NO adducts in septic RBCs were dependent on the inducible nitric oxide synthase
      and correlated with plasma nitrite, these findings provide a novel framework to
      understand mechanisms underlying dysfunctional blood flow responses during
      sepsis. Specifically, the concept that RBCs directly mediate systemic hypotension
      through NO-dependent mechanisms is discussed.

PMID- 15150084
TI  - Steps involved in immortalization and tumorigenesis in human B-lymphoblastoid
      cell lines transformed by Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) is closely associated with the generation of various
      tumors, including Burkitt's lymphoma. Human resting B cells from peripheral blood
      are easily transformed by EBV to actively proliferating B-lymphoblastoid cell
      lines (LCLs). These LCLs with normal diploid karyotypes have been believed to be
      "immortal", without becoming tumorigenic. A series of recent studies, however,
      indicate that this initial, simple concept needs extensive reconsideration. Most
      LCLs from normal individuals are mortal because their telomeres shorten. Some
      LCLs are truly immortalized by developing strong telomerase activity and
      aneuploidy, accompanied by various other changes: down-regulation of p16/Rb;
      mutation of the p53 gene; modulation of apoptosis; and sensitivity to various
      chemical agents. Some post-immortal LCLs additionally develop the ability to form
      colonies in agarose and even become tumorigenic by developing the ability to grow
      in nude mice. The genetic background of LCLs markedly affects the frequency of
      immortalization. In summary, changes of B cells after infection by EBV are
      roughly divided into two steps: (a) transformation of B cells into LCLs caused by
      EBV proteins; and (b) immortalization and tumorigenesis of LCLs mainly regulated
      by the factors of host cells in cooperation with EBV proteins. The new concept as
      reviewed here is essential for the future study of tumorigenesis by EBV.

PMID- 15150085
TI  - A small interfering RNA targeting vascular endothelial growth factor as cancer
      therapeutics.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role during normal
      embryonic angiogenesis and also in the pathological angiogenesis that occurs in a
      number of diseases, including cancer. We developed a novel VEGF blockade system
      using RNA interference. The small interfering RNA (siRNA) targeting human VEGF
      almost completely inhibited the secretion of VEGF in a human prostate cancer cell
      line, PC-3, whereas the control scramble siRNA showed no effects. The VEGF siRNA
      with atelocollagen dramatically suppressed tumor angiogenesis and tumor growth in
      a PC-3 s.c. xenograft model. Atelocollagen provided a beneficial delivering means
      by which stabilization and efficient transfection of the siRNA injected into the
      tumors were achieved.

PMID- 15150086
TI  - The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in
      transgenic mice and is overexpressed in human leukemia.
AB  - HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in
      transformation has not been established. We generated transgenic mice with HMG-I
      targeted to lymphoid cells. All seven informative founder HMG-I mice developed
      aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers
      and are transplantable. We also demonstrate that HMG-I mRNA and protein are
      increased in human acute lymphocytic leukemia samples. Our results show that HMG
      I functions as an oncogene and suggest that it contributes to the pathogenesis of
      leukemia and other cancers with increased HMG-I expression.

PMID- 15150087
TI  - Endogenous galectin-3 determines the routing of CD95 apoptotic signaling
      pathways.
AB  - Studies of CD95 (APO-1/Fas), a member of the death receptor family, have revealed
      that it is involved in two primary CD95 apoptotic signaling pathways, one
      regulated by the large amount of active caspase-8 (type I) formed at the death
      inducing signaling complex and the other by the apoptogenic activity of
      mitochondria (type II). To date, it is still unclear which pathway will be
      activated in response to an apoptotic insult. Here, we demonstrate that the
      antiapoptotic molecule galectin-3, which contains the four amino acid-anti-death
      motif (NWGR) conserved in the BH1 domain of the Bcl-2 member proteins, is
      expressed only in type I cells. Transfection of galectin-3 cDNA into galectin-3
      null cells (type II) resulted converting them to type I apoptotic phenotype. In
      addition, we show that galectin-3 is complexed with CD95 in vivo identifying
      galectin-3 as a novel CD95-binding partner that determines which of the CD95
      apoptotic signaling pathways the cell will select.

PMID- 15150088
TI  - Loss of tumorigenicity and metastatic potential in carcinoma cells expressing the
      extracellular domain of the type 1 insulin-like growth factor receptor.
AB  - The receptor for the type 1 insulin-like growth factor (IGF-IR) was identified as
      a major regulator of the malignant phenotype and a target for cancer therapy. In
      the present study, a novel IGF-IR mutant consisting of the entire extracellular
      domain of the receptor (IGFIR(933)) was genetically engineered and expressed in
      highly metastatic H-59 murine lung carcinoma cells. We show here that the cells
      expressed a truncated heterotetramer (beta(m)-alpha-alpha-beta(m)) that was
      secreted into the medium and could neutralize the effects of exogenous IGF-I,
      thus diminishing IGF-I-induced signaling and blocking IGF-I-mediated cellular
      functions such as cell proliferation, invasion, and survival. In vivo, tumor
      incidence and growth rate were markedly reduced in mice inoculated s.c. with H
      59/IGFIR(933) cells. Moreover, after the intrasplenic/portal inoculation of these
      cells, there was a 90% reduction in the incidence of hepatic metastases and a
      significant increase in the long-term, disease-free survival of the mice compared
      with controls. Our results identify the IGFIR(933) as a potent antitumorigenic
      and antimetastatic agent with potential applications for cancer gene therapy.

PMID- 15150089
TI  - Tumor necrosis factor-related apoptosis-inducing ligand: a novel mechanism for
      Bacillus Calmette-Guerin-induced antitumor activity.
AB  - Mycobacterium bovis Bacillus Calmette-Guerin (BCG) use in the treatment of
      bladder cancer was first reported in 1976, but the mechanism of the induced
      antitumor activity has still not been fully explained. BCG is a potent
      immunostimulant, normally producing a Th1 cytokine response, including IFN.
      Recent studies have shown CpG oligodeoxynucleotide induce tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) expression via IFN production. Given
      that Mycobacterial DNA contains high amounts of CpG motifs, we hypothesized that
      BCG's antitumor properties are akin to CpG oligodeoxynucleotide, where the
      cytokine response to BCG induces TRAIL up-regulation. Using ELISA, urine IFN
      gamma, and TRAIL levels were initially undetectable in BCG therapy patients but
      were high after later induction treatments. More importantly, patients that
      responded to BCG therapy had significantly higher urine TRAIL levels, which
      killed bladder tumor cells in vitro versus nonresponders. Flow cytometry of fresh
      urine revealed TRAIL-expressing neutrophils. Given these data, we propose TRAIL
      plays a role in BCG-induced antitumor effects.

PMID- 15150090
TI  - Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair
      status of human cells.
AB  - Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian
      cells to killing by several genotoxic substances. However, although MMR-deficient
      cells are approximately 100-fold more resistant to killing by S(N)1 type
      methylating agents than MMR-proficient controls, the sensitivity differences
      reported for the other agents were typically <2-fold. To test whether these
      differences were linked to factors other than MMR status, we studied the
      cytotoxicities of mitomycin C, chloroethylcyclohexyl nitrosourea, melphalan,
      psoralen-UVA, etoposide, camptothecin, ionizing radiation, and cis
      dichlorodiaminoplatinum (cisplatin) in a strictly isogenic system. We now report
      that MMR deficiency reproducibly desensitized cells solely to cisplatin.

PMID- 15150091
TI  - Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell
      lines reveals characteristic up-regulation of potential new marker genes
      including ERBB3.
AB  - Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of
      soft parts, represents a rare lesion of the musculoskeletal system usually
      affecting adolescents and young adults. CCSST is typified by a chromosomal
      t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma
      gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity
      in nontransformed cells is regulated by cyclic AMP. Our aim was to identify
      critical differentially expressed genes in CCSST tumor cells in comparison with
      other solid tumors affecting children and young adults to better understand
      signaling pathways regulating specific features of the development and
      progression of this tumor entity. We applied Affymetrix Human Genome U95Av2
      oligonucleotide microarrays representing approximately 12,000 genes to generate
      the expression profiles of the CCSST cell lines GG-62, DTC-1, KAO, MST2, MST3,
      and Su-CC-S1 in comparison with 8 neuroblastoma, 7 Ewing tumor, and 6
      osteosarcoma cell lines. Subsequent hierarchical clustering of microarray data
      clearly separated all four of the tumor types from each other and identified
      differentially expressed transcripts, which are characteristically up-regulated
      in CCSST. Statistical analysis revealed a group of 331 probe sets, representing
      approximately 300 significant (P < 0.001) differentially regulated genes, which
      clearly discriminated between the CCSST and other tumor samples. Besides genes
      that were already known to be highly expressed in CCSST, like S100A11 (S100
      protein) or MITF (microphthalmia-associated transcription factor), this group
      shows an obvious portion of genes that are involved in cyclic AMP response or
      regulation, in pigmentation processes, or in neuronal structure and signaling.
      Comparison with other expression profile analyses on neuroectodermal childhood
      tumors confirms the high robustness of this strategy to characterize tumor
      entities based on their gene expression. We found the avian erythroblastic
      leukemia viral oncogene homologue 3 (ERBB3) to be one of the most dramatically up
      regulated genes in CCSST. Quantitative real-time PCR and Northern blot analysis
      verified the mRNA abundance and confirmed the absence of the inhibitory
      transcript variant of this gene. The protein product of the member of the
      epidermal growth factor receptor family ERBB3 could be shown to be highly present
      in all of the CCSST cell lines investigated, as well as in 18 of 20 primary tumor
      biopsies. In conclusion, our data demonstrate new aspects of the phenotype and
      the biological behavior of CCSST and reveal ERBB3 to be a useful diagnostic
      marker.

PMID- 15150092
TI  - The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton
      organization.
AB  - hSNF5/INI1, which encodes a component of the ATP-dependent chromatin remodeling
      hSWI-SNF complex, is a tumor suppressor gene mutated in malignant rhabdoid
      tumors. We have developed a tetracycline-based hSNF5/INI1-inducible system in a
      hSNF5/INI1-deficient malignant rhabdoid tumor cell line and studied time course
      variation of 22,000 genes/expressed sequence tags upon hSNF5/INI1 induction. A
      total of 482 responsive genes were identified and further clustered into 9 groups
      of coregulated genes. Among genes with early and strong inductions, the use of a
      fusion protein with the hormone-binding domain of the estrogen receptor enabled
      the identification of a subset of direct targets regulated independently of de
      novo protein synthesis. We show that the G(1) arrest induced by hSNF5/INI1 is
      reversible and associated with the down-regulation of components of the DNA
      replication complex. We also identify an unsuspected role of hSNF5/INI1 in
      cytoskeleton organization. Indeed, induction of hSNF5/INI1 induces dramatic
      modifications of the cell shape including complete disruption of the actin stress
      fiber network and disappearance of focal adhesions associated with up-regulation
      of genes involved in the organization of the actin cytoskeleton. We document a
      strong decrease of Rho activity upon hSNF5/INI1 expression, suggesting that the
      regulation of this activity constitutes a crucial step of the hSNF5/INI1-induced
      reorganization of the actin network. This study identifies hSNF5/INI1 target
      genes and provides evidence that hSNF5/INI1 may modulate the cell cycle control
      and cytoskeleton organization through the regulation of the retinoblastoma
      protein-E2F and Rho pathways.

PMID- 15150093
TI  - Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are
      selected in Barrett's esophagus.
AB  - Neoplastic progression is an evolutionary process characterized by genomic
      instability and waves of clonal expansions carrying genetic and epigenetic
      lesions to fixation (100% of the cell population). However, an evolutionarily
      neutral lesion may also reach fixation if it spreads as a hitchhiker on a
      selective sweep. We sought to distinguish advantageous lesions from hitchhikers
      in the premalignant condition Barrett's esophagus. Patients (211) had biopsies
      taken at 2-cm intervals in their Barrett's segments. Purified epithelial cells
      were assayed for loss of heterozygosity and microsatellite shifts on chromosomes
      9 and 17, sequence mutations in CDKN2A/MTS1/INK4a (p16) and TP53 (p53), and
      methylation of the p16 promoter. We measured the expanse of a lesion in a
      Barrett's segment as the proportion of proliferating cells that carried a lesion
      in that locus. We then selected the lesion having expanses >90% in the greatest
      number of patients as our first putative advantageous lesion. We filtered out
      hitchhikers by removing all expanses of other lesions that did not occur
      independent of the advantageous lesion. The entire process was repeated on the
      remaining expanses to identify additional advantageous lesions. p16 loss of
      heterozygosity, promoter methylation, and sequence mutations have strong,
      independent, advantageous effects on Barrett's cells early in progression. Second
      lesions in p16 and p53 are associated with later selective sweeps. Virtually all
      of the other lesion expansions, including microsatellite shifts, could be
      explained as hitchhikers on p16 lesion clonal expansions. These techniques can be
      applied to any neoplasm.

PMID- 15150094
TI  - Different effects of point mutations within the B-Raf glycine-rich loop in
      colorectal tumors on mitogen-activated protein/extracellular signal-regulated
      kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB
      pathway and cellular transformation.
AB  - Recently, mutations in the B-Raf gene have been identified in a variety of human
      cancers, such as melanoma and colorectal carcinoma, and more than 80% of the B
      Raf mutations have been V599E. Although other mutations have been reported, their
      functional consequences are poorly understood. In our earlier study, we
      demonstrated that colon tumor-associated B-Raf mutations within the kinase
      activation segment are not necessarily associated with an increase in mitogen
      activated protein/extracellular signal-regulated kinase kinase/extracellular
      signal-regulated kinase (MEK/Erk) or nuclear factor kappaB (NFkappaB) signaling
      activity or in NIH3T3-transforming ability. In this study, we examined the effect
      of colon tumor-associated mutations within the B-Raf glycine-rich loop (G loop)
      on MEK/Erk and NFkappaB signaling and on the transformation of NIH3T3 fibroblasts
      or IEC-6 intestinal epithelial cells. Of the six G loop mutations examined, only
      the B-Raf G468A significantly increased MEK/Erk and NFkappaB signaling and NIH3T3
      transformation. Only this mutation induced transformed phenotypes of IEC-6 cells.
      In contrast, the B-Raf G468E mutation significantly decreased MEK/Erk signaling
      and NIH3T3 transformation and had no effect on NFkappaB signaling. The B-Raf
      F467C mutation moderately elevated MEK/Erk signaling and NIH3T3 transformation.
      The other three B-Raf mutations, R461I, I462S, and G463E, did not increase
      MEK/Erk or NFkappaB signaling or NIH3T3 transformation. Except for F467C, none of
      the tumors with B-Raf mutations examined in this study had K-Ras mutations. These
      results suggest that some of the B-Raf G loop mutations reported in colorectal
      tumors do not increase kinase or transforming activities but might contribute to
      carcinogenesis via other mechanisms or be irrelevant to carcinogenesis.

PMID- 15150096
TI  - Telomeric recombination in mismatch repair deficient human colon cancer cells
      after telomerase inhibition.
AB  - The majority of human malignancies use telomerase to maintain telomere
      homeostasis. Antitelomerase therapy is therefore a promising approach for a
      cancer-specific therapy. The alternative lengthening of telomeres pathway (ALT)
      is a recombination-based, telomerase-independent mechanism of telomere length
      control. It is widely believed that ALT could be engaged when cancer cells escape
      from telomerase inhibition. However, no reports exist that would support this
      concept of therapy resistance. We inhibited telomerase in a human cancer cell
      line with a mismatch repair defect and observed a telomerase-independent, ALT
      like telomere elongation. This is the first report of inducing a telomerase
      independent telomere elongation in human cancer cells when telomerase is
      inhibited, thus describing a novel mechanism of resistance to antitelomerase
      therapy.

PMID- 15150095
TI  - Perturbed IFN-gamma-Jak-signal transducers and activators of transcription
      signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin
      IFN-gamma treatment.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized
      by widespread development of hamartomas, which is caused by mutations in either
      TSC1 or TSC2. We demonstrate a dramatic decrease of IFN-gamma expression in
      tumors and mouse embryo fibroblast cell lines that lack either Tsc1 or Tsc2,
      which is reversed by rapamycin (mammalian target of rapamycin inhibitor) therapy.
      Increased signal transducers and activators of transcription (STAT) 1 expression
      and phosphorylation at Ser 727 and increased pSTAT3 Tyr705 levels also are seen
      in Tsc1 null and Tsc2 null cells and in tumors. Treatment of Tsc1 or Tsc2 null
      cells with IFN-gamma induces apoptosis, in contrast to control cell lines, with
      reduction in pSTAT3 Tyr705 levels and major increases in pSTAT1 Tyr701, bax, and
      caspase-1 and -9 levels. A combination of IFN-gamma and rapamycin is markedly
      synergistic in induction of apoptosis in Tsc1 or Tsc2 null cells because pSTAT3
      Tyr705 phosphorylation is abolished completely and the other effects of IFN-gamma
      are maintained or enhanced. Rapamycin-IFN-gamma has unique potential therapeutic
      benefit for management of TSC tumors.

PMID- 15150097
TI  - Antiapoptotic function of apoptosis inhibitor 2-MALT1 fusion protein involved in
      t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphoma.
AB  - t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa
      associated lymphoid tissue (MALT) type lymphoma, and this translocation results
      in fusion transcript of apoptosis inhibitor 2 (API2), also known as c-IAP2, and
      MALT translocation gene 1 (MALT1). Although the API2-MALT1 fusion protein has
      been shown to enforce activation of nuclear factor kappaB signaling, its precise
      role in the apoptotic signaling pathway remains to be established. To identify
      proteins that bind the API2-MALT1 protein, we used coimmunoprecipitation and SDS
      PAGE, followed by liquid chromatography-electrospray ionization tandem mass
      spectrometry. As a result, three important regulators of apoptosis, Smac, HtrA2,
      and TRAF2, and three other proteins were identified as potential API2-MALT1
      binding proteins. Immunoprecipitation analyses verified that API2-MALT1 indeed
      binds to both exogeneous and endogeneous Smac proteins. It is especially
      noteworthy that stably transfected API2-MALT1 significantly suppressed both UV-
      and etoposide-induced apoptosis in HeLa cells, thus demonstrating for the first
      time that API2-MALT1 indeed possesses antiapoptotic function. Furthermore, API2
      MALT1 significantly suppressed Smac-promoted apoptosis in UV-irradiated HeLa
      cells. Thus, our results provide direct experimental evidence that API2-MALT1 can
      confer resistance to apoptosis, at least in part, by neutralizing apoptosis
      promoted by Smac.

PMID- 15150098
TI  - Genetic analysis of macrophage characteristics as a tool to identify tumor
      susceptibility genes: mapping of three macrophage-associated risk inflammatory
      factors, marif1, marif2, and marif3.
AB  - Genetic predisposition to cancer is influenced by allelic variation in tumor
      susceptibility genes (TSGs) as present in the germline. We previously
      demonstrated in the mouse that TSGs frequently participate in genetic
      interactions, indicating that they represent molecular networks. Inflammation may
      constitute one of the molecular networks underlying susceptibility to cancer by
      influencing the tumor microenvironment. Because macrophages play a key role in
      inflammation and are often associated with tumors, we argue that a subset of TSGs
      can be identified by examining the genetics of macrophage characteristics. A
      panel of inflammation-related assays was established to phenotype mouse bone
      marrow-derived macrophages, which included stimulation with lipopolysaccharides
      followed by measurement of secretion of tumor necrosis factor alpha and the p40
      chain of interleukin-12 and of expression of inducible nitric oxide synthase and
      cyclooxygenase-2. This panel of assays was used for linkage analysis and applied
      to bone marrow-derived macrophages derived from individual mice of segregating
      crosses between inbred strain O20 and the highly related strains NTX-10 and NTX
      20, which differed from O20 in only 10% of their genome, to reduce genetic
      complexity. Three macrophage-associated risk inflammatory factors were mapped
      Marif1, Marif2, and Marif3-that each affected several inflammation-related
      assays, confirming that they function within molecular networks. Moreover, Marif1
      and Marif2 were localized in regions with established linkage for both
      quantitative and qualitative aspects of lung cancer susceptibility. These studies
      provide a novel approach to investigate the genetics of microenvironmental
      influence on predisposition to tumorigenesis, thereby contributing to development
      of new strategies that aim to prevent or treat cancer.

PMID- 15150099
TI  - Microarray analysis of epigenetic silencing of gene expression in the KAS-6/1
      multiple myeloma cell line.
AB  - The epigenetic control of gene transcription in cancer has been the theme of many
      recent studies and therapeutic approaches. Carcinogenesis is frequently
      associated with hypermethylation and consequent down-regulation of genes that
      prevent cancer, e.g., those that control cell proliferation and apoptosis. We
      used the demethylating drug zebularine to induce changes in DNA methylation, then
      examined patterns of gene expression using cDNA array analysis and Restriction
      Landmark Genomic Scanning followed by RNase protection assay and reverse
      transcription-PCR to confirm the results. Microarray studies revealed that many
      genes were epigenetically regulated by methylation. We concluded that methylation
      decreased the expression of, or silenced, several genes, contributing to the
      growth and survival of multiple myeloma cells. For example, a number of genes
      (BAD, BAK, BIK, and BAX) involved in apoptosis were found to be suppressed by
      methylation. Sequenced methylation-regulated DNA fragments identified by
      Restriction Landmark Genomic Scanning were found to contain CpG islands, and some
      corresponded to promoters of genes that were regulated by methylation. We also
      observed that after the removal of the demethylating drug, the addition of
      interleukin 6 restored CpG methylation and re-established previously silenced
      gene patterns, thus implicating a novel role of interleukin 6 in processes
      regulating epigenetic gene repression and carcinogenesis.

PMID- 15150100
TI  - Inhibition of Wnt-1 signaling induces apoptosis in beta-catenin-deficient
      mesothelioma cells.
AB  - It is known that Wnt-1 signaling inhibits apoptosis by activating beta
      catenin/tcf-mediated transcription. Here, we show that blocking Wnt-1 signaling
      in beta-catenin-deficient mesothelioma cell lines H28 and MS-1 induces apoptotic
      cell death. Both Wnt-1 small interfering RNA (siRNA) and Dishevelled siRNA
      induced significant apoptosis in these cell lines. A small molecule inhibitor of
      c-Jun NH(2)-terminal kinase inhibited the apoptotic cell killing induced by
      either Wnt-1 siRNA or Dishevelled siRNA in these cells. Our data suggest that
      beta-catenin-independent noncanonical pathway(s), i.e., Wnt/JNK pathway, may play
      a role in the apoptotic inhibition caused by Wnt-1 signaling.

PMID- 15150101
TI  - Lineage infidelity of MDA-MB-435 cells: expression of melanocyte proteins in a
      breast cancer cell line.
AB  - The origin of cell lines is critical in defining cell type-specific biological
      functions. Several reports suggested that the MDA-MB-435 cell line, a cell line
      extensively used for studying breast cancer biology, has a gene expression
      pattern most compatible with melanocyte origin. However, we demonstrate that MDA
      MB-435 cells express breast-specific or epithelial-specific markers. Also, MDA-MB
      435 cells were induced to express breast differentiation-specific proteins and
      secrete milk lipids as observed in other well-established breast cancer cell
      lines. Notably, MDA-MB-435 cells also expressed melanocyte-specific proteins as
      did another highly aggressive breast cancer cell line. MDA-MB-435 xenograft
      tissue sections stained entirely positive for epithelium-specific markers but
      only partially positive for melanocyte-specific markers. Thus, MDA-MB-435 is most
      likely a breast epithelial cell line that has undergone lineage infidelity.

PMID- 15150102
TI  - Serine/threonine kinase AKT is frequently activated in human bile duct cancer and
      is associated with increased radioresistance.
AB  - The prognosis for patients with bile duct cancer (BDC) remains poor. Although BDC
      cells are essentially radioresistant, recent reports have suggested that
      radiation therapy, in addition to its palliative role in the management of BDC,
      may improve patient survival. A better understanding of the mechanisms that lead
      to cellular radioresistance may assist in the development of more effective BDC
      therapies based on radiotherapy in combination with radiosensitizing agents. The
      serine/threonine kinase AKT/protein kinase B, a downstream effector of
      phosphatidylinositol 3'-kinase, is a well-characterized kinase that is known to
      play a critical role in antiapoptotic signaling pathways. In this investigation,
      we sought to clarify the role of AKT signaling in the radioresistance in BDC
      cells. First, to examine whether activated AKT is expressed in BDCs, tumor
      specimens were obtained from 19 consecutive BDC cases. Immunohistochemical
      staining using an anti-phosphorylated-AKT antibody showed that phosphorylated
      (activated) AKT was expressed in cancer cells but not in neighboring normal
      mucosa in 16 cases (84.2%). Next, to evaluate the role of AKT activation in the
      regulation of BDC cell radiosensitivity, clonogenic assays were performed using
      the phosphatidylinositol 3'-kinase inhibitor LY294002 with and without
      irradiation. LY294002 inhibited AKT activation in BDC cells and, on irradiation,
      decreased clonogenic survival in a radiation dose-dependent manner. Only a small
      decrease in cell viability was observed in cells exposed to LY294002. Expression
      of constitutively active AKT in BDC cells resulted in decreased radiosensitivity,
      whereas a dominant-negative AKT increased radiosensitivity. Furthermore,
      constitutively active AKT also inhibited radiation-induced apoptosis.
      Collectively, these results indicate that activated AKT in BDC cells is
      associated with radioresistance and suggest that pharmacological or genetic
      modulation of AKT activity may have important therapeutic implications in BDC
      patients treated with radiation.

PMID- 15150103
TI  - A novel protein tyrosine kinase NOK that shares homology with platelet- derived
      growth factor/fibroblast growth factor receptors induces tumorigenesis and
      metastasis in nude mice.
AB  - Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation
      of a variety of cellular processes including cell migration, proliferation, and
      protection from apoptosis. Here, we report the identification and
      characterization of a novel RPTK-like molecule that has a critical role in
      induction of tumorigenesis and metastasis and is termed Novel Oncogene with
      Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a
      conserved intracellular tyrosine kinase domain that shares homology with members
      of the platelet-derived growth factor/fibroblast growth factor receptor
      superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were
      detected in limited human organs and expressed with the highest abundance in the
      prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated
      that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the
      NOK gene as examined by colony formation experiment. In addition, BaF3 cells with
      the stable expression of NOK induced rapid tumorigenesis in nude mice.
      Interestingly, these NOK-expressing tumor cells could promptly invade and spread
      into various distinct organs and form metastatic foci, eventually leading to the
      rapid death of these animals. Moreover, molecular mechanism studies indicated
      that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3'
      kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and
      in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell
      transformation, tumorigenesis, and metastasis.

PMID- 15150104
TI  - Akt and hypoxia-inducible factor-1 independently enhance tumor growth and
      angiogenesis.
AB  - Recent reports have suggested that phosphatidylinositol 3-kinase/Akt signaling
      can induce angiogenesis and tumor growth by activating the hypoxia-inducible
      factor-1 (HIF-1). However, the absence of specific biochemical inhibitors of HIF
      1 signaling has prevented a direct test of the requirement for HIF-1 activity in
      Akt-dependent tumorigenesis. To genetically test the relationship between HIF-1
      and Akt, activated Akt was expressed in a hepatoma cell line lacking HIF-1. Akt
      expression was associated with a dramatic increase in tumor size, despite the
      absence of HIF-1. Tumor size was not further increased in cells with
      reconstituted HIF-1 activity, indicating that the effects of Akt on tumorigenesis
      were not limited by the absence of HIF-1. Increased tumor size in Akt-expressing,
      HIF-deficient cells was associated with vascular endothelial growth factor
      secretion and tumor vascularization. In addition to vascular endothelial growth
      factor production, Akt also conferred a cell-autonomous competitive advantage to
      tumor cells in an in vivo competition experiment. Thus, Akt has potent, HIF-1
      independent oncogenic and angiogenic activities.

PMID- 15150105
TI  - Loss of vascular endothelial growth factor a activity in murine epidermal
      keratinocytes delays wound healing and inhibits tumor formation.
AB  - The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a
      central role in both wound healing and tumor growth. In the skin, epidermal
      keratinocytes are a major source of this growth factor. To study the contribution
      of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we
      generated mice in which this cytokine was inactivated specifically in keratin 5
      expressing tissues. The mutant mice were macroscopically normal, and the skin
      capillary system was well established, demonstrating that keratinocyte-derived
      VEGF-A is not essential for angiogenesis in the skin during embryonic
      development. However, healing of full-thickness wounds in adult animals was
      appreciably delayed compared with controls, with retarded crust shedding and the
      appearance of a blood vessel-free zone underneath the newly formed epidermis.
      When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and
      promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice.
      In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice,
      whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant
      mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were
      found in seven of the control animals. These data demonstrate that whereas
      keratinocyte-derived VEGF-A is dispensable for skin vascularization under
      physiological conditions, it plays an important albeit nonessential role during
      epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2
      benzanthracene-induced epithelial skin tumors.

PMID- 15150106
TI  - Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance
      in human cholangiocarcinoma cells.
AB  - Cholangiocarcinomas are usually fatal neoplasms originating from bile duct
      epithelia. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      promising agent for cancer therapy, including cholangiocarcinoma. However, many
      cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Thus, our aim
      was to examine the intracellular mechanisms responsible for TRAIL resistance in
      human cholangiocarcinoma cell lines. Three TRAIL-resistant human
      cholangiocarcinoma cell lines were identified. All of the cell lines expressed
      TRAIL receptor 1/death receptor 4 (TRAIL-R1/DR4) and TRAIL-R2/DR5. Expression of
      TRAIL decoy receptors and the antiapoptotic cellular FLICE-inhibitory protein
      (cFLIP) was inconsistent across the cell lines. Of the antiapoptotic Bcl-2 family
      of proteins profiled (Bcl-2, Bcl-x(L), and Mcl-1), Mcl-1 was uniquely
      overexpressed by the cell lines. When small-interfering-RNA (siRNA) technology
      was used to knock down expression of Bcl-2, Bcl-x(L), and Mcl-1, only the Mcl-1
      siRNA sensitized the cells to TRAIL-mediated apoptosis. In a cell line stably
      transfected with Mcl-1-small-hairpin-RNA (Mcl-1-shRNA), Mcl-1 depletion
      sensitized cells to TRAIL-mediated apoptosis despite Bcl-2 expression. TRAIL
      mediated apoptosis in the stably transfected cells was associated with
      mitochondrial depolarization, Bax activation, cytochrome c release from
      mitochondria, and caspase activation. Finally, flavopiridol, an anticancer drug
      that rapidly down-regulates Mcl-1, also sensitized cells to TRAIL cytotoxicity.
      In conclusion, these studies not only demonstrate that Mcl-1 mediates TRAIL
      resistance in cholangiocarcinoma cells by blocking the mitochondrial pathway of
      cell death but also identify two strategies for circumventing this resistance.

PMID- 15150108
TI  - Expression of pigment epithelium-derived factor decreases liver metastasis and
      correlates with favorable prognosis for patients with ductal pancreatic
      adenocarcinoma.
AB  - Pigment epithelium-derived factor (PEDF) is expressed in several normal organs
      and identified as an inhibitor of neovascularization. In the present study, we
      screened the expression of PEDF immunohistochemically and investigated its
      correlation with clinicopathological features in patients who underwent surgery
      for ductal pancreatic adenocarcinoma. Of the 80 patients, 22 cases (27.5%) were
      positive for PEDF. A significant association was found between the PEDF
      expression and low microvessel density (P = 0.0003). No correlation was found
      between PEDF expression and age, gender, depth of invasion, tumor diameter,
      lymphatic invasion, venous, invasion or histopathological grading. The patients
      in pathological stage II had a significantly higher incidence of PEDF-positive
      expression than those in pathological stage III or IVA (P = 0.0418). PEDF
      immunoreactivity was inversely associated with liver metastasis (P = 0.0422). The
      survival of patients that were PEDF positive was significantly longer than that
      of those with negative expression (P = 0.0026). Multivariate analysis using the
      Cox regression model indicated that PEDF-positive expression was an independent
      favorable prognostic factor (risk ratio, 0.394; P = 0.0016). We conclude that
      PEDF expression suggests a more favorable prognosis than in patients whose
      carcinomas lack PEDF expression.

PMID- 15150107
TI  - Somatic mutation of p53 leads to estrogen receptor alpha-positive and -negative
      mouse mammary tumors with high frequency of metastasis.
AB  - Approximately 70% of human breast cancers are estrogen receptor alpha (ERalpha)
      positive, but the origins of ERalpha-positive and -negative tumors remain
      unclear. Hormonal regulation of mammary gland development in mice is similar to
      that in humans; however, most mouse models produce only ERalpha-negative tumors.
      In addition, these mouse tumors metastasize at a low rate relative to human
      breast tumors. We report here that somatic mutations of p53 in mouse mammary
      epithelial cells using the Cre/loxP system leads to ERalpha-positive and 
      negative tumors. p53 inactivation under a constitutive active WAPCre(c) in
      prepubertal/pubertal mice, but not under MMTVCre in adult mice, leads to the
      development of ERalpha-positive tumors, suggesting that target cells or
      developmental stages can determine ERalpha status in mammary tumors. Importantly,
      these tumors have a high rate of metastasis. An inverse relationship between the
      number of targeted cells and median tumor latency was also observed. Median tumor
      latency reaches a plateau when targeted cell numbers exceed 20%, implying the
      existence of saturation kinetics for breast carcinogenesis. Genetic alterations
      commonly observed in human breast cancer including c-myc amplification and
      Her2/Neu/erbB2 activation were seen in these mouse tumors. Thus, this tumor
      system reproduces many important features of human breast cancer and provides
      tools for the study of the origins of ERalpha-positive and -negative breast
      tumors in mice.

PMID- 15150109
TI  - The phosphoprotein StarD10 is overexpressed in breast cancer and cooperates with
      ErbB receptors in cellular transformation.
AB  - We have identified that StarD10, a member of the START protein family, is
      overexpressed in both mouse and human breast tumors. StarD10 was initially
      discovered on the basis of its cross-reactivity with a phosphoserine-specific
      antibody in mammary tumors from Neu/ErbB2 transgenic mice and subsequently
      isolated from SKBR3 human breast carcinoma cells using a multistep biochemical
      purification strategy. We have shown that StarD10 is capable of binding lipids.
      StarD10 was found to be overexpressed in 35% of primary breast carcinomas and 64%
      of human breast cancer cell lines, correlating with their ErbB2/Her2 status.
      Coexpression of StarD10 with ErbB1/epidermal growth factor receptor in murine
      fibroblasts enhanced anchorage-independent growth in soft agar, providing
      evidence for functional cooperation between StarD10 and ErbB receptor signaling.
      Taken together, these data suggest that overexpression of this lipid-binding
      protein contributes to breast oncogenesis.

PMID- 15150110
TI  - Expression of a novel human gene, human wings apart-like (hWAPL), is associated
      with cervical carcinogenesis and tumor progression.
AB  - In Drosophila melanogaster, the wings apart-like (wapl) gene encodes a protein
      that regulates heterochromatin structure. Here, we characterize a novel human
      homologue of wapl (termed human WAPL; hWAPL). The hWAPL mRNA was predominantly
      expressed in uterine cervical cancer, with weak expression in all other normal
      and tumor tissues examined. hWAPL expression in benign epithelia was confined to
      the basal cell layers, whereas in dysplasias it increasingly appeared in more
      superficial cell layers and showed a significant correlation with severity of
      dysplasia. Diffuse hWAPL expression was found in all invasive squamous cell
      carcinomas examined. In addition, NIH3T3 cells overexpressing hWAPL developed
      into tumors on injection into nude mice. Furthermore, repression of hWAPL
      expression by RNA interference induced cell death in SiHa cells. These results
      demonstrate that hWAPL is associated with cell growth, and the hWAPL expression
      may play a significant role in cervical carcinogenesis and tumor progression.

PMID- 15150111
TI  - Activated signal transducer and activator of transcription (STAT) 3: localization
      in focal adhesions and function in ovarian cancer cell motility.
AB  - Constitutive activation of the Janus-activated kinase/signal transducer and
      activator of transcription (STAT) pathway promotes the proliferation and survival
      of cancer cells in culture and is associated with various cancers, including
      those of the ovary. We found that constitutively activated STAT3 levels
      correlated with aggressive clinical behavior of ovarian carcinoma specimens.
      Furthermore, inhibition of STAT3 reduced the motility of ovarian cancer cells in
      vitro. Surprisingly, we found that activated STAT3 localized not only to nuclei
      but also to focal adhesions in these cells. Activated STAT3 coimmunoprecipitated
      with phosphorylated paxillin and focal adhesion kinase and required paxillin and
      Src for its localization to focal adhesions. These results suggest that Janus
      activated kinase/STAT signaling may contribute to ovarian cancer cell
      invasiveness.

PMID- 15150112
TI  - Functional analysis of novel sonic hedgehog gene mutations identified in basal
      cell carcinomas from xeroderma pigmentosum patients.
AB  - Altered sonic hedgehog (SHH) signaling is crucial in the development of basal
      cell carcinomas (BCC), the most common human cancer. Mutations in SHH signal
      transducers, PATCHED and SMOOTHENED, have already been identified, but SHH
      mutations are extremely rare; only 1 was detected in 74 sporadic BCCs. We present
      data showing unique SHH mutations in BCCs from repair-deficient, skin cancer
      prone xeroderma pigmentosum (XP) patients, which are characterized by high levels
      of UV-specific mutations in key genes involved in skin carcinogenesis, including
      PATCHED and SMOOTHENED. Thus, 6 UV-specific SHH mutations were detected in 5 of
      33 XP BCCs. These missense SHH alterations are not activating mutations for its
      postulated proto-oncogene function, as the mutant SHH proteins do not show
      transforming activity and induce differentiation or stimulate proliferation to
      the same level as the wild-type protein. Structural modeling studies of the 4
      proteins altered at the surface residues, G57S, G64K, D147N, and R155C, show that
      they do not effect the protein conformation. Interestingly, they are all located
      on one face of the compact SHH protein suggesting that they may have altered
      affinity for different partners, which may be important in altering other
      functions. Additional functional analysis of the SHH mutations found in vivo in
      XP BCCs will help shed light on the role of SHH in skin carcinogenesis. In
      conclusion, we report for the first time, significant levels of SHH mutations
      found only in XP BCCs and none in squamous cell carcinomas, indicating their
      importance in the specific development of BCCs.

PMID- 15150114
TI  - Laminin-induced signaling in tumor cells: the role of the M(r) 67,000 laminin
      receptor.
AB  - The expression of the M(r) 67,000 laminin receptor, a nonintegrin laminin
      receptor, was found to be up-regulated in neoplastic cells and to directly
      correlate with invasion and metastatic potential. In the present study, we
      investigated the role of laminin receptor in mediating laminin effects and the
      involvement of the mitogen-activated protein kinases (MAPK) cascades and dual
      specificity phosphatases in laminin signaling in human melanoma cells. Using
      stable transfection of A375SM melanoma cells, we established lines expressing
      reduced or elevated laminin receptor. The antisense-transfected cells
      demonstrated reduced attachment to laminin and reduced invasion through Matrigel
      coated filters. In addition, both matrix metalloproteinase-2 (MMP-2) mRNA
      expression and activity were significantly reduced in the antisense-transfected
      cells. Antisense-transfected cells showed a reduction in mRNA level of the
      alpha6B integrin subunit isoform, whereas no change in the mRNA level of the
      alpha6A isoform was observed. We found that exogenous laminin reduced the
      phosphorylated (active) form of extracellular signal-regulated kinase, c-Jun
      NH(2)-terminal protein kinase, and p38 in all of the cells, irrespective of the
      expression of the laminin receptor. Furthermore, the phosphorylation of
      extracellular signal-regulated kinase, c-Jun NH(2)-terminal protein kinase, and
      p38 was significantly higher in the cell lines expressing reduced laminin
      receptor, regardless of the exposure to exogenous laminin. This increase of MAPK
      phosphorylation was accompanied by a significant reduction in MKP-1 phosphatase
      mRNA level and a significant increase in PAC-1 phosphatase mRNA level. In
      conclusion, our results confirm the involvement of the laminin receptor in
      different mechanisms related to tumor dissemination and provide first evidence of
      the involvement of MAPK and dual-specificity phosphatases in its signal
      transduction pathway.

PMID- 15150113
TI  - The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268
      cooperate to promote transforming growth factor beta-dependent apoptosis in
      breast cancer.
AB  - We show that the selective estrogen receptor modulator arzoxifene (Arz) and the
      rexinoid LG100268 (268) synergize to promote apoptosis in a rat model of estrogen
      receptor-positive breast carcinoma and in estrogen receptor-positive human breast
      cancer cells in culture. We also show that it is not necessary to administer Arz
      and 268 continuously during tumor progression to prevent cancer in the rat model
      because dosing of these drugs in combination for relatively short periods, each
      followed by drug-free rests, is highly effective. This new approach to
      chemoprevention uses high doses of drugs that are too toxic for long-term
      administration. However, when given for short periods, the agents are nontoxic
      and still induce apoptosis in breast cancer cells. We also show that the ability
      of the two drugs to induce apoptosis is the combined result of induction of
      transforming growth factor beta by Arz, together with inhibition of the
      prosurvival nuclear factor kappaB and phosphatidylinositol 3' kinase signaling
      pathways by 268. The new protocol we have developed for chemoprevention allows
      the efficacious and safe administration of 268 and Arz, and these agents now
      should be considered for clinical use.

PMID- 15150115
TI  - The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene
      transformation.
AB  - The activated Ras oncogene can transform various mammalian cells and has been
      implicated in development of a high population of malignant human tumors. Recent
      studies suggest that generation of reactive oxygen species such as superoxide and
      H(2)O(2) is involved in cell transformation by the activated Ras. However, the
      nature of an oxidase participating in Ras-transformation is presently unknown.
      Here, we report that Ras oncogene up-regulates the expression of Nox1, a
      homologue of the catalytic subunit of the superoxide-generating NADPH oxidase,
      via the mitogen-activated protein kinase kinase-mitogen-activated protein kinase
      pathway, and that small interfering RNAs designed to target Nox1 mRNA effectively
      blocks the Ras transformed phenotypes including anchorage-independent growth,
      morphological changes, and production of tumors in athymic mice. Therefore, we
      propose that increased reactive oxygen species generation by Ras-induced Nox1 is
      required for oncogenic Ras transformation.

PMID- 15150116
TI  - Blocking angiogenesis and tumorigenesis with GFA-116, a synthetic molecule that
      inhibits binding of vascular endothelial growth factor to its receptor.
AB  - A small synthetic library of cyclohexapeptidomimetic calixarenes was prepared to
      identify disrupters of vascular endothelial growth factor (VEGF) binding to its
      receptor that inhibits angiogenesis. From this library, we discovered GFA-116,
      which potently inhibits (125)I-VEGF binding to Flk-1 in Flk-1-overexpressing NIH
      3T3 cells and human prostate tumor cells with an IC(50) of 750 nM. This
      inhibition is highly selective for VEGF in that (125)I- platelet-derived growth
      factor binding to its receptor is not affected. GFA-116 inhibits VEGF-stimulated
      Flk-1 tyrosine phosphorylation and subsequent activation of Erk1/2 mitogen
      activated protein kinases. Furthermore, epidermal growth factor, platelet-derived
      growth factor, and fibroblast growth factor-dependent stimulation of Erk1/2
      phosphorylation are not affected at concentrations as high as 10 microM. In
      vitro, GFA-116 inhibits angiogenesis as measured by inhibition of migration and
      formation of capillary-like structures by human endothelial cells as well as
      suppression of microvessel outgrowth in rat aortic rings and rat cornea
      angiogenesis. In vivo, GFA-116 (50 mpk/day) inhibits tumor growth and
      angiogenesis as measured by CD31 staining of A-549 human lung tumors in nude
      mice. Furthermore, GFA-116 is also effective at inhibiting tumor growth and
      metastasis to the lung of B16-F10 melanoma cells injected into immunocompetent
      mice. Taken together, these results demonstrate that a synthetic molecule capable
      of disrupting the binding of VEGF to its receptor selectively inhibits VEGF
      dependent signaling and suppresses angiogenesis and tumorigenesis.

PMID- 15150117
TI  - Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human
      colon cancer cells.
AB  - We have shown previously that the death receptor CD95 could contribute to
      anticancer drug-induced apoptosis of colon cancer cells. In addition, anticancer
      drugs cooperate with CD95 cognate ligand or agonistic antibodies to trigger
      cancer cell apoptosis. In the present study, we show that the anticancer drug
      cisplatin induces clustering of CD95 at the surface of the human colon cancer
      cell line HT29, an event inhibited by the inhibitor of acid sphingomyelinase
      (aSMase) imipramine. The cholesterol sequestering agent nystatin also prevents
      cisplatin-induced CD95 clustering and decreases HT29 cell sensitivity to
      cisplatin-induced apoptosis and the synergy between cisplatin and anti-CD95
      agonistic antibodies. CD95, together with the adaptor molecule Fas-associated
      death domain and procaspase-8, is redistributed into cholesterol- and
      sphingolipid-enriched cell fractions after cisplatin treatment, suggesting plasma
      membrane raft involvement. Interestingly, nystatin prevents the translocation of
      the aSMase to the extracellular surface of plasma membrane and the production of
      ceramide, suggesting that these early events require raft integrity. In addition,
      nystatin prevents cisplatin-induced transient increase in plasma membrane
      fluidity that could be required for CD95 translocation. Together, these results
      demonstrate that cisplatin activates aSMase and induces ceramide production,
      which triggers the redistribution of CD95 into the plasma membrane rafts. Such
      redistribution contributes to cell death and sensitizes tumor cells to CD95
      mediated apoptosis.

PMID- 15150118
TI  - Thioredoxin is downstream of Smad7 in a pathway that promotes growth and
      suppresses cisplatin-induced apoptosis in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human malignancy in
      which Smad7 is commonly overexpressed. Analysis by differential display
      identified thioredoxin-1 (TRX) as a gene whose basal expression is increased in
      COLO-357 pancreatic cancer cells engineered to overexpress Smad7. To delineate
      the biological consequences of TRX overexpression, we assessed TRX mRNA levels in
      PDAC and studied the effects of increased TRX levels in Smad7-overexpressing
      cells. By northern blotting, TRX mRNA levels were increased in PDAC samples by
      comparison with the normal pancreas. Moreover, analysis of laser-captured
      pancreatic cancer cells revealed parallel increases in Smad7 and TRX mRNA levels.
      Retroviral infection of an antisense TRX cDNA suppressed TRX protein levels and
      blunted the increased capacity of Smad7-overexpressing cells to form colonies in
      soft agar. 1-Methyl-propyl-2-imidazolozyl disulfide, a TRX inhibitor, markedly
      suppressed the growth of sham-transfected COLO-357 cells and enhanced the growth
      inhibitory actions of cis-diamminedichloroplatinum(II) (CDDP). CDDP also induced
      apoptosis, as evidenced by induction of DNA laddering, PARP cleavage, and caspase
      3/9 activities. These pro-apoptotic actions were greatly attenuated in Smad7
      overexpressing cells, which exhibited a more prolonged association of TRX with
      the apoptosis inducer apoptosis signal-regulating kinase-1, and enhanced nuclear
      factor kappaB activation in response to CDDP. These findings suggest that TRX is
      downstream of Smad7 in a pathway that confers a growth advantage to pancreatic
      cancer cells and that increases their resistance to CDDP-mediated apoptosis,
      implying novel regulatory functions for Smad7.

PMID- 15150119
TI  - Bcl-2 inhibitors sensitize tumor necrosis factor-related apoptosis-inducing
      ligand-induced apoptosis by uncoupling of mitochondrial respiration in human
      leukemic CEM cells.
AB  - Previous studies have shown that the lymphoblastic leukemia CEM cell line is
      resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      induced apoptosis because of a low expression of caspase-8. Bcl-2 inhibitors,
      BH3I-2' and HA14-1, are small cell-permeable nonpeptide compounds, are able to
      induce apoptosis by mediating cytochrome c release, and also lead to dissipation
      of the mitochondrial membrane potential (DeltaPsim). This study aimed to use the
      Bcl-2 inhibitors to sensitize CEM cells to TRAIL-induced apoptosis by switching
      on the mitochondrial apoptotic pathway. We found that a low dose of BH3I-2' or
      HA14-1, which did not induce cytochrome c release, greatly sensitized CEM cells
      to TRAIL-induced apoptosis. In a similar manner to the classical uncoupler
      carbonyl cyanide m-chlorophenylhydrazone (CCCP), both BH3I-2' and HA14-1 induced
      a reduction in DeltaPsim, a generation of reactive oxygen species (ROS), an
      increased mitochondrial respiration, and a decreased ATP synthesis. This
      uncoupling function of the Bcl-2 inhibitors was responsible for the synergy with
      TRAIL-induced apoptosis. CCCP per se did not induce apoptosis but again
      sensitized CEM cells to TRAIL-induced apoptosis by uncoupling mitochondrial
      respiration. The uncoupling effect facilitated TRAIL-induced Bax conformational
      change and cytochrome c release from mitochondria. Inhibition of caspases failed
      to block TRAIL-mediated cell death when mitochondrial respiration was uncoupled.
      We observed that BH3I-2', HA14-1, or CCCP can overcome resistance to TRAIL
      induced apoptosis in TRAIL-resistant cell lines, such as CEM, HL-60, and U937.
      Our results suggest that the uncoupling of mitochondrial respiration can
      sensitize leukemic cells to TRAIL-induced apoptosis. However, caspase activation
      per se does not represent an irreversible point of commitment to TRAIL-induced
      cell death when mitochondrial respiration is uncoupled.

PMID- 15150120
TI  - Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrene
      detoxification pathway.
AB  - Glycine N-methyltransferase (GNMT) affects genetic stability by (a) regulating
      the ratio of S-adenosylmethionine to S-adenosylhomocystine and (b) binding to
      folate. Based on the identification of GNMT as a 4 S polyaromatic hydrocarbon
      binding protein, we used liver cancer cell lines that expressed GNMT either
      transiently or stably in cDNA transfections to analyze the role of GNMT in the
      benzo(a)pyrene (BaP) detoxification pathway. Results from an indirect
      immunofluorescent antibody assay showed that GNMT was expressed in cell cytoplasm
      before BaP treatment and translocated to cell nuclei after BaP treatment.
      Compared with cells transfected with the vector plasmid, the number of BaP-7,8
      diol 9,10-epoxide-DNA adducts that formed in GNMT-expressing cells was
      significantly reduced. Furthermore, the dose-dependent inhibition of BaP-7,8-diol
      9,10-epoxide-DNA adduct formation by GNMT was observed in HepG2 cells infected
      with different multiplicities of infection of recombinant adenoviruses carrying
      GNMT cDNA. According to an aryl hydrocarbon hydroxylase enzyme activity assay,
      GNMT inhibited BaP-induced cytochrome P450 1A1 enzyme activity. Automated BaP
      docking using a Lamarckian genetic algorithm with GNMT X-ray crystallography
      revealed a BaP preference for the S-adenosylmethionine-binding domain of the
      dimeric form of GNMT, a novel finding of a cellular defense against potentially
      damaging exposures. In addition to GNMT, results from docking experiments showed
      that BaP binds readily with other DNA methyltransferases, including HhaI, HaeIII,
      PvuII methyltransferases and human DNA methyltransferase 2. We therefore
      hypothesized that BaP-DNA methyltransferase and BaP-GNMT interactions may
      contribute to carcinogenesis.

PMID- 15150121
TI  - Transduction of soluble Flt-1 gene to peritoneal mesothelial cells can
      effectively suppress peritoneal metastasis of gastric cancer.
AB  - The prognosis of gastric cancer with peritoneal metastasis has not improved.
      Despite many promising studies, gene therapy has limited clinical application
      because of the lack of suitable vector systems to enable selective gene
      transduction to tumor cells. The aim of this study was to clarify whether gene
      therapy targeted to peritoneal mesothelial cells (PMCs) can inhibit peritoneal
      dissemination of gastric cancer. In vitro experiments showed that adenovirus
      expressing LacZ infected human omental tissue-derived PMCs more efficiently than
      human gastric cancer cell lines MKN1 and MKN45. When adenovirus expressing LacZ
      was injected into the peritoneal cavity of nude mice, the expression was detected
      in the peritoneum for at least 4 weeks. Furthermore, when adenovirus expressing
      soluble Flt-1 (Ad-sFLT-1) was i.p. administered in vivo, a high level of sFlt-1
      protein could be detected in peritoneal lavage for 8 weeks. When MKN45 cells were
      i.p. inoculated 3 days after adenoviral vector injection, Ad-sFLT-1 markedly
      reduced the number of metastatic nodules larger than 1 mm in diameter on the
      peritoneal surface, and significantly prolonged the survival of nude mice without
      any significant side effects. Thus, peritoneal dissemination was significantly
      suppressed by a single i.p. injection of Ad-sFlt-1. Anti-angiogenic gene therapy
      targeted to PMCs could be a novel and practical strategy against peritoneal
      dissemination of gastric cancer, because it does not require tumor-specific gene
      transfer.

PMID- 15150122
TI  - UCN-01-induced cell cycle arrest requires the transcriptional induction of
      p21(waf1/cip1) by activation of mitogen-activated protein/extracellular signal
      regulated kinase kinase/extracellular signal-regulated kinase pathway.
AB  - The small molecule UCN-01 is a cyclin-dependent kinase (CDK) modulator shown to
      have antiproliferative effects against several in vitro and in vivo cancer models
      currently being tested in human clinical trials. Although UCN-01 may inhibit
      several serine-threonine kinases, the exact mechanism by which it promotes cell
      cycle arrest is still unclear. We have reported previously that UCN-01 promotes
      G(1)-S cell cycle arrest in a battery of head and neck squamous cancer cell
      lines. The arrest is accompanied by an increase in both p21(waf1/cip1) and
      p27(kip1) CDK inhibitors leading to loss in G(1) CDK activity. In this report, we
      explore the role and the mechanism for the induction of these endogenous CDK
      inhibitors. We observed that p21 was required for the cell cycle effects of UCN
      01, as HCT116 lacking p21 (HCT116 p21(-/-)) was refractory to the cell cycle
      effects of UCN-01. Moreover, UCN-01 promoted the accumulation of p21 at the mRNA
      level in the p53-deficient HaCaT cells without increase in the p21 mRNA half
      life, suggesting that UCN-01 induced p21 at the transcriptional level. To study
      UCN-01 transcriptional activation of p21, we used several p21(waf1/cip1) promoter
      driven luciferase reporter plasmids and observed that UCN-01 activated the full
      length p21(waf1/cip1) promoter and a construct lacking p53 binding sites. The
      minimal promoter region required for UCN-01 (from -110 bp to the transcription
      start site) was the same minimal p21(waf1/cip1) promoter region required for Ras
      enhancement of p21(waf1/cip1) transcription. Neither protein kinase C nor
      PDK1/AKT pathways were relevant for the induction of p21 by UCN-01. In contrast,
      the activation of mitogen-activated protein/extracellular signal-regulated kinase
      kinase (MEK)/extracellular signal-regulated kinase mitogen-activated protein
      kinase pathways was required for p21 induction as UCN-01 activated this pathway,
      and genetic or chemical MEK inhibitors blunted p21 accumulation. These results
      demonstrated for the first time that p21 is required for UCN-01 cell cycle
      arrest. Moreover, we showed that the accumulation of p21 is transcriptional via
      activation of the MEK pathway. This novel mechanism, by which UCN-01 exerts its
      antiproliferative effect, represents a promising strategy to be exploited in
      future clinical trials.

PMID- 15150123
TI  - An oncolytic adenovirus vector combining enhanced cell-to-cell spreading,
      mediated by the ADP cytolytic protein, with selective replication in cancer cells
      with deregulated wnt signaling.
AB  - We have constructed a novel oncolytic adenovirus (Ad) vector named VRX-009 that
      combines enhanced cell spread with tumor-specific replication. Enhanced spread,
      which could significantly increase antitumor efficacy, is mediated by
      overexpression of the Ad cytolytic protein named ADP (also known as E3-11.6K).
      Replication of VRX-009 is restricted to cells with a deregulated wnt signal
      transduction pathway by replacement of the wild-type Ad E4 promoter with a
      synthetic promoter consisting of five consensus binding sites for the T-cell
      factor transcription factor. Tumor-selective replication is indicated by several
      lines of evidence. VRX-009 expresses E4ORF3, a representative Ad E4 protein, only
      in colon cancer cell lines. Furthermore, VRX-009 replicates preferentially in
      colon cancer cell lines as evidenced by virus productivity 2 orders of magnitude
      higher in SW480 colon cancer cells than in A549 lung cancer cells. Replication in
      primary human bronchial epithelial cells and human umbilical vein endothelial
      cells was also significantly lower than in SW480 cells. When tested in human
      tumor xenografts in nude mice, VRX-009 effectively suppressed the growth of SW480
      colon tumors but not of A549 lung tumors. VRX-009 may provide greater level of
      antitumor efficacy than standard oncolytic Ad vectors in tumors in which a defect
      in wnt signaling increases the level of nuclear beta-catenin.

PMID- 15150125
TI  - Flavopiridol induces p53 via initial inhibition of Mdm2 and p21 and,
      independently of p53, sensitizes apoptosis-reluctant cells to tumor necrosis
      factor.
AB  - Flavopiridol (FP) inhibits gene expression and causes apoptosis, and these
      effects cannot be explained by inhibition of cyclin-dependent kinases that govern
      cell cycle. The simple and established notion that FP is an inhibitor of
      transcription predicts its effects. Because Mdm-2 targets p53 for degradation,
      FP, as predicted, dramatically induced p53 by inhibiting Mdm-2. Once p53 was
      induced, restoration of transcription (by removal of FP) resulted in
      superinduction of p21 and Mdm-2. Similarly, low concentrations of FP (50 nm)
      induced p21 and Mdm-2 because of their initial down-regulation. A sustained
      decrease of Mdm-2/p21 expression and accumulation of p53 coincided with near
      maximal cytotoxicity of FP at concentrations >100 nm. Induction of p53 was a
      marker, not a cause, of cytotoxicity. FP caused rapid apoptosis (caspase
      dependent cell death) in p53-null leukemia cells. In these cells, FP-induced
      apoptosis was converted to growth arrest by inhibitors of caspases. In apoptosis
      reluctant A549 and PC3M cancer cells, FP inhibited cell proliferation but did not
      cause apoptosis. Like typical inhibitors of transcription, FP sensitized cells to
      apoptotic stimuli, allowing tumor necrosis factor to cause rapid and massive
      apoptosis in otherwise apoptosis-reluctant cells. We discuss that, as a
      reversible inhibitor of transcription, FP can be used clinically in novel
      rational drug combinations.

PMID- 15150126
TI  - Microarray analysis reveals differences in gene expression of circulating CD8(+)
      T cells in melanoma patients and healthy donors.
AB  - Circulating T cells from many cancer patients are known to be dysfunctional and
      undergo spontaneous apoptosis. We used microarray technology to determine whether
      gene expression differences exist in T cells from melanoma patients versus
      healthy subjects, which may underlie these abnormalities. To maximize the
      resolution of our data, we sort purified CD8(+) subsets and amplified the
      extracted RNA for microarray analysis. These analyses show subtle but
      statistically significant expression differences for 10 genes in T cells from
      melanoma patients versus healthy controls, which were additionally confirmed by
      quantitative real-time PCR analysis. Whereas none of these genes are members of
      the classical apoptosis pathways, several may be linked to apoptosis. To
      additionally investigate the significance of these 10 genes, we combined them
      into a classifier and found that they provide a much better discrimination
      between melanoma and healthy T cells as compared with a classifier built uniquely
      with classical apoptosis-related genes. These results suggest the possible
      engagement of an alternative apoptosis pathway in circulating T cells from cancer
      patients.

PMID- 15150124
TI  - Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor
      PKC412 is highly effective against human acute myelogenous leukemia cells with
      mutant FLT-3.
AB  - Presence of the activating length mutation (LM) in the juxtamembrane domain or
      point mutation in the kinase domain of FMS-like tyrosine kinase-3 (FLT-3)
      mediates ligand-independent progrowth and prosurvival signaling in approximately
      one-third of acute myelogenous leukemia (AML). PKC412, an inhibitor of FLT-3
      kinase activity, is being clinically evaluated in AML. Present studies
      demonstrate that treatment of human acute leukemia MV4-11 cells (containing a FLT
      3 LM) with the heat shock protein 90 inhibitor 17-allylamino-demethoxy
      geldanamycin (17-AAG) attenuated the levels of FLT-3 by inhibiting its chaperone
      association with heat shock protein 90, which induced the poly-ubiquitylation and
      proteasomal degradation of FLT-3. Treatment with 17-AAG induced cell cycle G(1)
      phase accumulation and apoptosis of MV4-11 cells. 17-AAG-mediated attenuation of
      FLT-3 and p-FLT-3 in MV4-11 cells was associated with decrease in the levels of p
      AKT, p-ERK1/2, and p-STAT5, as well as attenuation of the DNA binding activity of
      STAT-5. Treatment with 17-AAG, downstream of STAT5, reduced the levels of c-Myc
      and oncostatin M, which are transactivated by STAT5. Cotreatment with 17-AAG and
      PKC412 markedly down-regulated the levels of FLT-3, p-FLT-3, p-AKT, p-ERK1/2, and
      p-STAT5, as well as induced more apoptosis of MV4-11 cells than either agent
      alone. Furthermore, the combination of 17-AAG and PKC412 exerted synergistic
      cytotoxic effects against MV4-11 cells. Importantly, 17-AAG and PKC412 induced
      more loss of cell viability of primary AML blasts containing FLT-3 LM, as
      compared with those that contained wild-type FLT-3. Collectively, these in vitro
      findings indicate that the combination of 17-AAG and PKC412 has high level of
      activity against AML cells with FLT-3 mutations.

PMID- 15150127
TI  - Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor
      (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.
AB  - The present study was designed to determine whether: (a) chronic administration
      of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug,
      which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host
      immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to
      impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis
      coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with
      lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels
      in their splenic T cells. Responses of splenic T, B, and natural killer cells to
      broad-based and antigen-specific stimuli were, for the most part, unchanged in
      those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN
      gamma production by concanavalin A- or antigen-stimulated T cells; and (b)
      heightened lipopolysaccharide response of naive B cells from mice fed a diet
      supplemented with 1000 ppm of celecoxib. When transgenic mice that express the
      human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice
      bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia
      mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously
      develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning
      at 30 days of age, the administration of a diversified prime/boost recombinant
      CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet
      reduced the number of intestinal neoplasms by 54% and 65%, respectively.
      Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced
      tumor burden by 95% and significantly improved overall long-term survival. Both
      tumor reduction and improved overall survival were achieved without any evidence
      of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is
      prescribed for the treatment of familial adenomatous polyposis in humans, and the
      CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA
      host immune responses in early clinical studies. The results suggest that the
      administration of a recombinant poxvirus-based vaccine is compatible with
      celecoxib, and this combined chemoimmuno-based approach might lead to an additive
      therapeutic antitumor benefit not only in patients diagnosed with familial
      adenomatous polyposis but, perhaps, in other preventive settings in which COX-2
      overexpression is associated with progression from premalignancy to neoplasia.

PMID- 15150128
TI  - Endothelial cell surface ATP synthase-triggered caspase-apoptotic pathway is
      essential for k1-5-induced antiangiogenesis.
AB  - We have recently reported the identification of kringle 1-5 (K1-5) of plasminogen
      as a potent and specific inhibitor of angiogenesis and tumor growth. Here, we
      show that K1-5 bound to endothelial cell surface ATP synthase and triggered
      caspase-mediated endothelial cell apoptosis. Induction of endothelial apoptosis
      involved sequential activation of caspases-8, -9, and -3. Administration of
      neutralizing antibodies directed against the alpha- and beta-subunits of ATP
      synthase to endothelial cells attenuated activation of these caspases.
      Furthermore, inhibitors of caspases-3, -8, and -9 also remarkably blocked K1-5
      induced endothelial cell apoptosis and antiangiogenic responses. In a mouse tumor
      model, we show that caspase-3 inhibitors abolished the antitumor activity of K1-5
      by protecting the tumor vasculature undergoing apoptosis. These results suggest
      that the specificity of the antiendothelial effect of K1-5 is attributable, at
      least in part, to its interaction with the endothelial cell surface ATP synthase
      and that the caspase-mediated endothelial apoptosis is essential for the
      angiostatic activity of K1-5. Thus, our findings provide a mechanistic insight
      with respect to the angiostatic action and signaling pathway of K1-5 and
      angiostatin.

PMID- 15150129
TI  - ECL-cell derived gastric cancer in male cotton rats dosed with the H2-blocker
      loxtidine.
AB  - Spontaneously hypergastrinemic cotton rats (Sigmodon hispidus) develop tumors
      that have the phenotype of an adenocarcinoma but most likely originate from the
      enterochromaffin-like (ECL) cells. Among inbred animals approximately 50% of the
      females, but <1% of males develop spontaneous gastric carcinomas. Gastrin is the
      principle carcinogen in this model, as >4 months of hypergastrinemia results in
      carcinoma, but a gastrin receptor antagonist prevents carcinomas. Carcinomas can
      also be induced by partial corpectomy. In the present study, the insurmountable
      H2-receptor antagonist loxtidine (200 mg/kg/day) was given to male cotton rats
      for 6 months. The loxtidine-dosed animals developed hypergastrinemia, whereas
      control animals remained normogastrinemic. At termination, 4 of 5 cotton rats had
      cancer located to the oxyntic mucosa, whereas 1 animal had dysplasia. The gastric
      mucosa of all of the control animals was normal. In the dysplastic mucosa of
      loxtidine-dosed animals there was a marked increase in chromogranin A-positive
      cells, where numerous groups of cells also stained positive with the Sevier
      Munger technique. In areas of high proliferation and cancer there were also
      histidine decarboxylase, chromogranin A, and Sevier-Munger-positive cells,
      altogether indicating an ECL cell origin of the tumors. This represents an
      interesting animal model where ECL cell-derived gastric cancer can be induced by
      pharmacological acid inhibition in 6 months.

PMID- 15150130
TI  - Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice
      and human cancer patients.
AB  - The expression of many genes is altered in colon cancer, but the roles of these
      genes in carcinogenesis are unclear. Using real-time quantitative PCR, we
      demonstrated that several genes previously implicated in human colon cancer
      undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor
      of cancer, as well as in normal-appearing surrounding mucosa. The five genes that
      were most highly up-regulated in mouse polyp were also significantly up-regulated
      in polyp-free colon mucosa. Similar changes occurred in morphologically normal
      mucosa of surgical sections taken from human cancer patients, frequently
      extending to the margins. Thus, morphologically normal colon mucosa in APC(min)
      mice and in human cancer patients is not metabolically normal. Altered gene
      expression in this tissue does not appear to result from a field effect because
      there was no correlation between extent of altered regulation and distance from
      polyp or tumor. Our data suggest that alterations of expression levels of these
      genes may be an early event in carcinogenesis and a marker of risk for the
      development of colon cancer.

PMID- 15150131
TI  - Transactivation of the PPAR-responsive enhancer module in chemopreventive
      glutathione S-transferase gene by the peroxisome proliferator-activated receptor
      gamma and retinoid X receptor heterodimer.
AB  - Cancer chemopreventive agents transcriptionally induce glutathione S-transferase
      (GST), which can protect cells from chemical-induced carcinogenesis. Activation
      of either NF-E2-related factor-2 (Nrf2) or the CCAAT/enhancer binding protein
      beta (C/EBPbeta) contributes to GST induction. Peroxisome proliferator-activated
      receptor-gamma (PPARgamma) and the retinoic acid X receptor (RXR) play roles in
      regulating cell differentiation and chemoprevention. This study examined GSTA2
      gene induction by the PPARgamma activator and 9-cis-retinoic acid (RA), a RXR
      ligand, and investigated the molecular basis of PPAR-RXR-mediated GSTA2 induction
      in the H4IIE hepatocytes. Either 15-deoxy-delta (12, 14)-prostaglandin J(2)
      (PGJ(2)) or RA induced GSTA2 with Nrf2 and C/EBPbeta activation. When compared
      with PGJ(2) or RA alone, PGJ(2) + RA enhanced GSTA2 induction, with increases in
      Nrf2 and C/EBPbeta activation. PGJ(2) + RA increased the luciferase reporter gene
      activity in the cells transfected with the -1.65-kb flanking region of the GSTA2
      gene. Thiazolidinedione PPARgamma agonists, troglitazone, rosiglitazone, and
      pioglitazone, in combination with RA, potentiated GSTA2 induction, confirming
      that the activation of the PPARgamma and RXR heterodimer contributed to GSTA2
      expression. Deletion of the antioxidant response element- or C/EBP-binding sites
      or the overexpression of dominant-negative mutant of C/EBP abolished the reporter
      gene expression. PGJ2 + RA increased the binding of the PPARgamma - RXR
      heterodimer to the putative PPAR-response elements (PPREs) in the GSTA2 promoter.
      Specific mutations of these multiple PPRE sites resulted in the complete loss of
      its responsiveness to PGJ2 + RA, which suggests that these binding sites function
      as a PPRE-responsive enhancer module (PPREM). Transactivation of PPREM by the
      PPARgamma - RXR heterodimer was verified by the effective GSTA2 induction in the
      cells treated with PGJ2 + RA after transfecting them with the plasmids encoding
      PPARgamma1 and RXRalpha. In conclusion, the PPARgamma - RXR heterodimer promotes
      GSTA2 induction by activating PPREM in the GSTA2 gene, as well as inducing Nrf2
      and C/EBPbeta activation.

PMID- 15150132
TI  - Chemopreventive effects of a selective nitric oxide synthase inhibitor on
      carcinogen-induced rat esophageal tumorigenesis.
AB  - The inducible nitric oxide synthase (iNOS) generates a high concentration of
      nitric oxide (NO) in tissues. Increased NO production is associated with many
      disorders including esophageal cancer. Previous studies in our laboratory
      demonstrated an association between increased iNOS expression and the development
      of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. On the
      basis of these observations, we initiated a bioassay to evaluate the ability of
      S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), a selective iNOS
      inhibitor, to prevent the progression of esophageal tumors in rats preinitiated
      with NMBA. Rats were given s.c. injections of NMBA (0.25 mg/kg body weight) three
      times per week for 5 weeks. One week later, they were fed a synthetic diet
      containing either 50 or 100 ppm PBIT until the end of the bioassay (25 weeks).
      PBIT reduced the incidence of esophageal cancer from 96% in NMBA-treated rats to
      83% and 77% (P < 0.05) in rats treated with 50 and 100 ppm PBIT, respectively.
      Tumor multiplicity was reduced from 3.64 +/- 0.42 tumors per esophagus in NMBA
      treated rats to 1.79 +/- 0.25 (P < 0.001) and 1.50 +/- 0.24 (P < 0.0001) in rats
      treated with 50 and 100 ppm PBIT, respectively. PBIT reduced the production of NO
      in NMBA-induced preneoplastic and papillomatous esophageal lesions when compared
      with comparable lesions in rats treated with NMBA only. iNOS mRNA expression was
      not modulated by PBIT. These observations suggest that iNOS plays a role in tumor
      development and that its selective inhibitor, PBIT, significantly inhibits
      esophageal tumor progression presumably through reducing the production of NO.

PMID- 15150133
TI  - Comparative pathology of nerve sheath tumors in mouse models and humans.
AB  - Despite the progress made in our understanding of the biology of
      neurofibromatosis (NF), the long-term clinical outcome for affected patients has
      not changed significantly in the past decades, and both NF1 and NF2 are still
      associated with a significant morbidity and a decreased life span. A number of
      NF1 and NF2 murine models have been generated to aid in the study of NF tumor
      biology and in the development of targeted therapies for NF patients. A single,
      universal pathological classification of the lesions generated in these murine
      models is essential for the validation of the models, for their analysis and
      comparison with other models, and for their future effective use in preclinical
      treatment trials. For the formulation of a pathological classification of these
      lesions, the WHO classification of human tumors was used as a reference. However,
      it was not adopted for the classification of the GEM lesions because of some
      important differences between the human and murine lesions. A novel
      classification scheme for peripheral nerve sheath tumors in murine models was
      therefore devised.

PMID- 15150134
TI  - Evaluating community coalition characteristics and functioning: a summary of
      measurement tools.
AB  - Community coalitions and partnerships are frequently used to promote community
      health; however, little research to evaluate measurement tools for assessing
      their effectiveness has been reported. This summary identified measurement tools
      for coalition or partnership characteristics and functioning. The largest numbers
      of measures were identified for assessing individual and group characteristics,
      with impact and outcome measures being the least numerous. Published measures
      often lacked information regarding validity and reliability, with internal
      consistency reliability being the most commonly reported statistic. Some measures
      were well defined, but others lacked conceptual clarity. Valid and reliable tools
      that can be applied across multiple coalitions are necessary in order to achieve
      a better understanding of the associations among factors influencing optimal
      coalition functioning and community health impacts and outcomes.

PMID- 15150135
TI  - Social cohesion and intrapersonal empowerment: gender as moderator.
AB  - Health educators have embraced empowerment as an alternative to traditional
      frameworks that place greater emphasis on individual health behaviors than socio
      political factors that promote or constrain life-style choices. A critical
      element of empowerment theory for health educators is the participatory process
      in which people might engage to improve quality of life. As a piece of
      participatory process, social cohesion is an emerging construct that links
      community participation with notions of trust, shared emotional commitment and
      reciprocity. This study builds on prior research by exploring whether gender
      interacts with social cohesion to predict intrapersonal empowerment. Data were
      collected from interviews with randomly selected community residents. Extending
      previous studies, the findings showed that the effects of social cohesion on
      intrapersonal empowerment were different for females and males. Implications for
      community interventions and directions for future research are discussed.

PMID- 15150136
TI  - Teaching a coherent theory of drug action to elementary school children.
AB  - This study examined whether two versions of a drug and alcohol curriculum
      explaining how substances affect behavior and health, one version more causally
      coherent than the other, were more effective than a control curriculum on disease
      in changing school-age children's (N=327) beliefs and attitudes regarding cocaine
      and alcohol. Few differences were found between the two drug and alcohol
      curricula. Compared to children receiving the control curriculum, however, both
      treatment groups demonstrated greater understanding of the circulation of alcohol
      and cocaine throughout the body, the true long-term effects of these substances,
      and the stimulant effects of cocaine. Moreover, they had less positive attitudes
      and intentions toward cocaine. Several differences were evident at both a 3-month
      post-test and a 1-year follow-up, pointing to the potential value of applying an
      intuitive theories perspective in designing drug prevention and other health
      education programs.

PMID- 15150137
TI  - The protective effect of parental expectations against early adolescent smoking
      initiation.
AB  - Substantial research and theory suggests that smoking initiation is socially
      mediated, with both peers and parents playing important roles. To learn more
      about how parenting behaviors influence smoking initiation, students (n=1002)
      from four middle schools were surveyed at the beginning of the sixth grade (T1),
      and the end of the sixth (T2) and seventh (T3) grades. T1 and T2-T1 predictors
      were regressed on smoking initiation at the end of seventh grade. In bivariate
      logistic regression analyses, association with friends who smoke, attitudes
      toward deviance, outcome expectations for smoking, perceived school climate,
      parental expectations, parental involvement at T1 and increases in these
      variables (T2-T1) were associated with smoking initiation at T3, but only the T1
      measures of social competence, academic engagement, school adjustment, perceived
      prevalence, parental monitoring and parental involvement were associated with
      smoking initiation at T3. In multivariate logistic regression analyses, parental
      expectations were negatively associated, and increases in attitudes accepting of
      deviance and affiliation with friends who smoke were positively associated with
      smoking initiation. Analysis of interactions indicated that parental expectations
      and monitoring did not mediate the effect on smoking initiation of attitudes
      toward deviance or the number of friends who smoke. These findings provide
      evidence that parental expectations may protect early adolescents against smoking
      even in the context of increases in favorable attitudes and friends who smoking.

PMID- 15150138
TI  - Severe acute respiratory syndrome epidemic and change of people's health behavior
      in China.
AB  - Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic
      whose origin was until recently unknown. It is the unpredictable nature of this
      epidemic that makes people want answers to some important questions about what
      they can do to protect themselves. This study presents an inquiry into people's
      knowledge and self-reported changes in behavior in response to the epidemic.
      Respondents were drawn from seven major occupational groups in the large central
      city of Wuhan. Although most respondents knew of SARS, there was still 8.4% who
      did not know about it. Knowledge was lowest among farmers who had come to the
      city for temporary work. Most respondents took action to avoid being infected by
      SARS, including, most commonly, efforts to improve indoor ventilation, to
      disinfect the indoor environment and to increase hand-washing frequency. Self
      reported increases in hand-washing frequency were significant; however, among the
      seven occupational groups, reports of increased hand-washing were consistently
      greater among commercial service workers, students and farmers. While it seems
      that possible fears induced by the epidemic led to these changes, there are still
      about one-third of respondents who do not wash their hands as frequently as
      desired. There is also the challenge of devising strategies for maintaining the
      desired frequency of hand-washing among those who did change.

PMID- 15150139
TI  - Patient communication: a multidisciplinary approach using animated cartoons.
AB  - Communication is a major problem in the management of patients. Miscommunication
      occurs frequently in populations with low reading skills, illiteracy does not
      completely account for the observed low rates of recall of communicated
      information. Transmission of the message also plays an important role. Successful
      strategies to improve communication with patients include the use of videotapes,
      videotape modeling or cartoon illustrations. Do these products communicate
      effectively because they overcome illiteracy or because they also transmit a very
      clear message? Can good transmission of messages overcome illiteracy? In this
      study, we compared the effectiveness of a printed message about polio
      vaccinations with the same message converted into a production of animated
      cartoons using marketing and advertising techniques. The production that resulted
      from using this strategy showed that in the setting of this study, a well
      designed animated cartoon is more effective in delivering a message than the same
      information provided in written instructional materials.

PMID- 15150140
TI  - Fine forecasts: encouraging the media to include ultraviolet radiation
      information in summertime weather forecasts.
AB  - Melanoma and skin cancer are largely attributable to over-exposure to solar
      ultraviolet radiation (UVR). Reports of UVR levels within media weather forecasts
      appear to be well received by the public and have good potential to communicate
      the need for appropriate sun protection to a broad audience. This study describes
      provision of UVR messages by New Zealand newspapers, radio and TV stations over a
      4-year period, and examines the impact of an intervention which aimed to address
      media concerns about the financial costs of accessing UVR information for
      broadcast. Newspaper and radio presentation of UVR information increased
      immediately after these costs were removed; however, among radio stations it
      dropped in subsequent years. Among those media that were presenting UVR, this
      information was broadcast throughout the summer period and repeated throughout
      the day. Furthermore, most reports included concomitant, behavioral sun
      protection messages. At the final assessment (summer 2001/02), 66% of radio
      stations, both TV channels and 48% of newspapers reported UVR information in
      summertime weather reports. Efforts to further increase UVR presentation will
      need to address media concerns about time constraints on weather forecasts and
      media perceptions of poor audience demand or understanding of some UVR messages.

PMID- 15150141
TI  - Making sense of olfaction through predictions of the 3-D structure and function
      of olfactory receptors.
AB  - We used the MembStruk first principles computational technique to predict the
      three-dimensional (3-D) structure of six mouse olfactory receptors (S6, S18, S19,
      S25, S46 and S50) for which experimental odorant recognition profiles are
      available for a set of 24 odorants (4-9 carbons aliphatic alcohols, acids, bromo
      acids and diacids). We used the HierDock method to scan each predicted OR
      structure for potential odorant binding site(s) and to calculate binding energies
      of each odorant in these binding sites. The calculated binding affinity profiles
      are in good agreement with experimental activation profiles, validating the
      predicted 3-D structures and the predicted binding sites. For each of the six
      ORs, the binding site is located between trans-membrane domains (TMs) 3-6, with
      contributions from extracellular loops 2 and 3. In particular, we find six
      residue positions in TM3 and TM6 to be consistently involved in the binding modes
      of the odorants. Indeed, the differences in the experimental recognition profiles
      can be explained on the basis of these critical residues alone. These predictions
      are also consistent with mutation data on ligand binding for catecholamine
      receptors and sequence hypervariability studies for ORs. Based on this analysis,
      we defined amino acid patterns associated with the recognition of short aliphatic
      alcohols and mono-acids. Using these two sequence fingerprints to probe the
      alignment of 869 OR sequences from the mouse genome, we identified 34 OR
      sequences matching the fingerprint for aliphatic mono-acids and 36 corresponding
      to the recognition pattern for aliphatic alcohols. We suggest that these two sets
      of ORs might function as basic arrays for uniquely recognizing aliphatic alcohols
      and acids. We screened a library of 89 additional molecules against the six ORs
      and found that this set of ORs is likely to respond to aldehydes and esters with
      longer carbon chains than their currently known agonists. We also find that
      compounds associated with the flavor in foods are often among the best calculated
      binding affinities. This suggests that physiologic ligands for these ORs may be
      found among aldehydes and esters associated with flavor.

PMID- 15150142
TI  - Glutamate taste: Discrimination between the tastes of glutamate agonists and
      monosodium glutamate in rats.
AB  - Taste aversion studies have demonstrated that rats conditioned to avoid
      monosodium glutamate (MSG) with amiloride added to reduce the intensity of the
      sodium component of MSG taste, generalize this aversion to aspartic acid and to L
      AP4, but not to ionotropic glutamate receptor agonists. That is, MSG, L-AP4 and
      aspartate have similar tastes to rats. However, conditioned taste aversion
      methods are unable to show to what extent the tastes of two substances are
      different. If two substances activate the same afferent processes (e.g. taste
      receptors), they are likely to produce the same tastes, but if they activate
      different afferent processes, the subject may detect differences between the
      tastes of the substances. In this study, rats were tested to determine if they
      could discriminate between the tastes of these agonists and MSG. We also
      established the detection thresholds for NMDA, aspartic acid and L-AP4, with and
      without amiloride (a sodium channel antagonist). Taste threshold values were 1-4
      mM for NMDA and aspartic acid and 0.5-2.5 microM for L-AP4. None were affected by
      30 micro M amiloride. Rats could readily distinguish between the tastes of MSG
      and NMDA but they had difficulty discriminating between the tastes of aspartic
      acid and MSG. Rats could also easily distinguish between 10-100 mM MSG and 0.01-5
      mM L-AP4. However, in two separate experiments error rates increased
      significantly when L-AP4 concentrations were between 10-100 mM, indicating that
      the tastes of L-AP4 and MSG were similar at these concentrations.

PMID- 15150143
TI  - Morphological evidence for two types of Mammalian vomeronasal system.
AB  - The vomeronasal (VN) systems of rodents and opossums are of the segregated type,
      i.e alpha-subtype G protein Gi2- or Go-expressing VN neurons, which are sensory
      cells, project discretely to the rostral or caudal region of the accessory
      olfactory bulb (AOB). Although this zone-specific projection is believed to be a
      common feature for processing pheromones in mammals, we previously found a
      uniform-type VN system in goat in which only Gi2-expressing VN axons terminate at
      the AOB. In most mammals, it remains unclear whether their VN systems are of the
      segregated or uniform type. Therefore, we investigated morphologically the VN
      systems of different mammalian species (dog, horse, musk shrew and common
      marmoset). Consequently, all VN axons of the examined animals were positively
      stained with immunohistochemistry for Gi2 in the same way as that in the goat. On
      the other hand, we observed immunoreactivities against Go in the olfactory axons,
      but not in the VN axons. These results suggest that many mammals have uniform
      type VN systems, and at least two types of VN systems exist in terrestrial
      mammals. This morphological evidence will help us determine the processing
      function of VN systems.

PMID- 15150144
TI  - A simple and reliable method for clinical assessment of odor thresholds.
AB  - We investigated whether presenting of dilutions of phenyl ethyl alcohol at random
      succession according to the method of constant stimuli can replace the standard
      procedure of presenting a various number of dilutions in a staircase paradigm.
      Forty-six men and 44 women, aged 19-76 years, participated in this study. Phenyl
      ethyl alcohol was diluted in a ratio of 1:2, starting from 4%. Presentation of
      the odorant followed a three-alternative, temporal forced-choice paradigm with
      two blanks in addition to the odorant. Twenty dilutions were administered in a
      randomized order. Odor threshold was obtained by logistic regression of the
      correct and incorrect identifications of the probe containing the odorant.
      Thresholds were also calculated on the basis of the first 16 dilution steps only.
      Results from these procedures were compared with 'gold-standard' threshold
      assessment employing a three-alternative, temporal forced-choice staircase
      paradigm with seven reversals using 16 dilutions of phenyl ethyl alcohol. The
      method of constant stimuli took a shorter and less variable testing time than the
      staircase technique. The use of 20 dilution steps provided no better results than
      the use of 16 steps. The method of constant stimuli exhibited a good test-retest
      reliability (r = 0.7; P < 0.001) comparable to that of the staircase method and
      provided unbiased results highly correlated (r = 0.8; P < 0.001) with those of
      the staircase technique with similar inter-test variability. Applying 16
      dilutions (1:2 steps) of phenyl ethyl alcohol at random succession in a three
      alternative, temporal forced-choice paradigm is thus a simple and reliable
      procedure for the reproducible assessment of odor thresholds that may be
      contemplated as an alternative to the 'gold-standard' staircase method of
      clinical odor threshold assessment.

PMID- 15150145
TI  - The response of the blood-sucking bug Triatoma infestans to carbon dioxide and
      other host odours.
AB  - Behavioural responses of Triatoma infestans larvae to carbon dioxide and other
      odours of vertebrate origin were investigated in a locomotion compensator. T.
      infestans oriented towards airstreams enriched with carbon dioxide exhibiting a
      threshold response between 300 and 400 p.p.m. above the ambient CO(2) background.
      The accuracy of the oriented response to carbon dioxide improved with stimulus
      intensity. Remarkably, insects did not show any change in their sensitivity
      threshold to carbon dioxide with the starvation time. The attractiveness to
      carbon dioxide depended on the time of the day, i.e. these nocturnal bugs only
      oriented towards carbon dioxide-loaded airstreams during the first hours of the
      scotophase. L-lactic acid did not evoke oriented responses when it was presented
      as a single stimulus in a wide range of intensities. However, a marked synergism
      was evident when L-lactic acid was combined with a sub-threshold concentration of
      carbon dioxide. Under this condition, the threshold response to carbon dioxide
      decreased to 75-150 p.p.m. above ambient CO(2) background. The isomer D-lactic
      acid evoked no response, either alone or in combination with carbon dioxide. When
      insects were stimulated with 1-octen-3-ol a significant positive orientation was
      found. This response was not modified by the addition of carbon dioxide.

PMID- 15150146
TI  - Odor-taste interactions: effects of attentional strategies during exposure.
AB  - Through repeated pairings with a tastant such as sucrose, odors are able to take
      on the tastant's qualities, e.g. by becoming more sweet smelling. When such odors
      are subsequently experienced with a sweet tastant in solution, the mixture is
      often given a higher sweetness rating than the tastant alone. Odor-induced taste
      enhancement appears to be sensitive to whether an odor-taste combination is
      viewed analytically as a set of discrete qualities, or synthetically as a flavor.
      The present research attempted to determine if adoption of these different
      perceptual approaches during co-exposure with sucrose would influence the extent
      to which an odor would become sweet smelling and subsequently enhance sweetness
      intensity. In Experiment 1, subjects received multiple exposures to mixtures of
      sucrose with low sweetness, low familiarity odors or, as a control, the odors and
      sucrose solutions separately. Two groups that received mixtures made intensity
      ratings that promoted either synthesis or analysis of the individual elements in
      the mixtures. The odors became sweeter smelling irrespective of group. Only
      adopting a synthetic strategy produced odors that enhanced sweetness in solution.
      However, these effects were also shown with a 'non-exposed' control odor. This
      could be accounted for if the single co-exposure with sucrose that all odors
      received in the pre-test was able to produce sweeter odors. A second experiment
      confirmed this prediction. Thus, while even a single co-exposure with sucrose is
      sufficient to produce a sweeter odor, the adoption of a synthetic perceptual
      strategy during the co-exposure is necessary to produce an odor that will enhance
      sweetness. These data are consistent with associative leaning accounts of how
      odors take on taste qualities and also support the interpretation that these
      effects reflect the central integration of odors and tastes into flavors.

PMID- 15150147
TI  - Newborn rabbit responsiveness to the mammary pheromone is concentration
      dependent.
AB  - The effect of the intensity of odour signals has rarely been investigated in the
      regulation of odour-guided behaviour in young mammals. This series of experiments
      used the mammary pheromone (MP) of the female rabbit to assess the influence of
      stimulus concentration on neonatal pup responsiveness. The MP is a single
      compound isolated from rabbit milk that releases in pups the typical head
      searching and oral seizing behaviour. The pups (n = 621) were exposed to graded
      concentrations of the MP in bioassays varying in stimulus delivery conditions.
      Experiment 1 demonstrated that in aqueous dilutions the MP efficiently elicits
      behavioural responses only within a limited range of concentrations (from 2.5 x
      10(-9) to 2.5 x 10(-5) g/ml). Experiment 2 yielded the same outcome with highly
      purified MP delivered in dynamic conditions with a gas chromatograph. Finally,
      Experiment 3 used deodorized milk as the solvent of the MP; despite this change
      in the physico-chemical context of stimulation, similar results were reached.

PMID- 15150149
TI  - Writing a research article: advice to beginners.

PMID- 15150148
TI  - Effects of acetazolamide and 4-aminopyridine on CO2-induced slowly adapting
      pulmonary stretch receptor inhibition in rats.
AB  - Inhibitory responses of slowly adapting pulmonary stretch receptor (SAR) activity
      to CO(2) inhalation (maximal tracheal CO(2) concentration ranging from 9.5 to
      12.5%) for approximately 60 s were examined before and after administration of
      acetazolamide (a carbonic anhydrase inhibitor) or 4-aminopyridine (4-AP, a K(+)
      channel blocker). The experiments were performed in 35 anesthetized, artificially
      ventilated rats after unilateral vagotomy. Sixty-eight of eighty-four SARs were
      inhibited by CO(2) inhalation. The SAR inhibition was attenuated by pretreatment
      with either acetazolamide (20 mg/kg, n = 10) or 4-AP (0.7 and 2.0 mg/kg, n = 10).
      In other series of experiments, stainings to show the existence of carbonic
      anhydrase (CA) enzymatic reaction were not found in the smooth muscle of either
      extrapulmonary or intrapulmonary bronchi. Protein gene product 9.5 (PGP 9.5)
      immunoreactive SAR terminals to form leaflike extensions were found in the
      bronchioles at different diameters and were smooth-muscle-related receptors. But
      in the same sections, CA isozyme II-like (erythrocyte CA) immunoreactive SAR
      terminals were not identified. These results suggest that CO(2)-induced
      inhibition of SARs may be involved in the CA-dependent CO(2) hydration in
      addition to the activation of 4-AP sensitive K(+) currents.

PMID- 15150150
TI  - Uptake of new treatment strategies for deep vein thrombosis: an international
      audit.
AB  - OBJECTIVE: Study of the uptake of new medical technologies provides useful
      information on the transfer of published evidence into usual practice. We
      conducted an audit of selected hospitals in three countries (Canada, France, and
      Switzerland) to identify clinical predictors of low-molecular-weight (LMW)
      heparin use and outpatient treatment, and to compare the pace of uptake of these
      new therapeutic approaches across hospitals. DESIGN: Historical review of medical
      records. SETTING AND PARTICIPANTS: We reviewed the medical records of 3043
      patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French,
      and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored
      independent clinical variables associated with LMW heparin use and outpatient
      treatment, and determined crude and adjusted rates of LMW heparin use and
      outpatient treatment across hospitals. RESULTS: For the years studied, the
      overall rates of LMW heparin use and outpatient treatment in the study sample
      were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many
      comorbidities were negatively associated with outpatient treatment, and risk
      adjusted rates of use of these new approaches varied significantly across
      hospitals. CONCLUSION: There has been a relatively rapid uptake of LMW heparins
      and outpatient treatment for DVT in their early years of availability, but the
      pace of uptake has varied considerably across hospitals and countries.

PMID- 15150151
TI  - Outcomes and the quality of care for patients hospitalized with heart failure.
AB  - OBJECTIVE: The purpose of this study was to determine whether process quality
      indicators derived from evidence-based guidelines for heart failure patients were
      associated with outcome indicators (hospital mortality and readmissions). DESIGN:
      A retrospective cohort-study among patients discharged with a primary or
      secondary International Classification of Disease, 10th revision (ICD-10) heart
      failure code from 1 January to 31 December 1999. SETTING: The study was
      implemented in three Swiss academic medical centers. STUDY PARTICIPANTS: Records
      of 1634 patients hospitalized with heart failure were abstracted. Demographic
      characteristics, risk factors, symptoms and findings at admission, and discharge
      characteristics were recorded. Main outcome measure. Process quality indicators
      were derived from evidence-based guidelines, related to appropriate management
      and treatment of heart failure patients. Hospital mortality was measured in a
      chart abstraction process. Thirty-day readmissions were calculated using
      administrative data from hospitals. RESULTS: Among the three hospitals, 1153
      patients with heart failure were eligible for this study. Mean age was 75.3 years
      (standard deviation 12.7) and 45.7% of patients were female. Ventricular function
      (VF) was determined in 69% of patients. The adjusted odds-ratios (OR) for the VF
      not determined were 1.74 [95% confidence interval (CI) 1.06-2.84] for hospital
      mortality and 0.75 (95% CI 0.47-1.18) for 30-day readmissions. Among patients
      with left ventricular systolic dysfunction and no contraindication to angiotensin
      converting enzyme inhibitor (ACEI), 54% were prescribed target-dose ACEI or
      angiotensin receptor blockers at discharge, 32% received ACEI at less then target
      dose, and 14% received no ACEI at discharge. Adjusted ORs (95% CI) for
      readmissions were 0.89 (0.28-2.84) for no ACEI and 1.17 (0.56-2.43) for less than
      target ACEI compared with target dose. CONCLUSIONS: Among patients with heart
      failure, the determination of VF was associated with hospital mortality. However,
      process indicators derived from evidence-based guidelines were not related to
      early readmissions in three Swiss university hospitals.

PMID- 15150152
TI  - A pressure ulcer audit and feedback project across multi-hospital settings in the
      Netherlands.
AB  - OBJECTIVE: To examine whether participating in a pressure ulcer prevalence survey
      and receiving feedback results in an improvement in quality of care. DESIGN:
      Cross-sectional studies from 1998 to 2002 were compared over time. SETTING: Sixty
      two acute care hospitals in the Netherlands. STUDY PARTICIPANTS: Patients
      hospitalized at the moment of the surveys. INTERVENTIONS: Each hospital was given
      hospital-specific performance data and national aggregate data, and peer
      comparisons to improve the quality of care. MAIN OUTCOME MEASURES: The case-mix
      adjusted prevalence of pressure ulcers of grade >or=2, the percentage of high
      risk patients receiving adequate prevention, and the total number of enabling
      conditions present were compared between successive surveys using multi-level
      analysis, in order to estimate a linear trend model and trend differences for
      each hospital. RESULTS: The case-mix-adjusted prevalence of pressure ulcers
      decreased over the 5-year period, while the percentage of patients receiving
      adequate prevention and the total number of enabling conditions present
      increased. The total number of enabling conditions had a significant effect on
      the decrease in case-mix-adjusted prevalence: more enabling conditions led to a
      lower case-mix-adjusted prevalence (chi(2) = 125; degrees of freedom = 1; P <
      0.00). The percentage of patients receiving adequate prevention also had an
      effect on the change in case-mix-adjusted prevalence, with a higher percentage
      leading to a lower case-mix-adjusted prevalence. This effect, however, was not
      significant. CONCLUSIONS: Monitoring prevalence and giving feedback results in an
      improvement in quality of care in terms of pressure ulcer prevention. It is very
      important to continue conducting surveys to avoid attention moving away from this
      topic, which may in turn lead to a deterioration in the quality of pressure ulcer
      care. Further research to find the most effective feedback approach is needed.

PMID- 15150153
TI  - The applicability of the Consumer Assessments of Health Plans Survey (CAHPS) to
      Preferred Provider Organizations in the United States: a discussion of industry
      concerns.
AB  - OBJECTIVE: This paper examines the applicability of a leading patient survey, the
      Consumer Assessments of Health Plans Study (CAHPS), to Preferred Provider
      Organizations (PPOs) in the United States. DESIGN: Elite interviews were
      conducted with users of the CAHPS survey in PPO settings. STUDY PARTICIPANTS:
      Study participants attended either the California Healthcare Foundation Quality
      Performance Measurement in Preferred Provider Organizations Forum or the National
      Conference to Examine PPO Quality. Eleven representatives of state and federal
      government health care purchasers, commercial PPO plans, and survey vendors were
      included. MAIN OUTCOME MEASURES: The interview included 21 questions addressing
      experiences with and concerns about using the CAHPS survey in PPO settings.
      RESULTS: Respondents raised concerns about the influence of out-of-network care
      on CAHPS reports and ratings of PPO health plans. Suggestions were made for
      additional PPO-relevant items such as after-hours care, numbers and types of
      specialists in the PPO network, and disease management. CONCLUSIONS:
      Modifications to some of the CAHPS survey items are needed to address concerns of
      users about their applicability in PPO settings.

PMID- 15150154
TI  - Physicians' views on joint treatment guidelines for primary and secondary care.
AB  - OBJECTIVE: Joint drug formularies and treatment guidelines have been developed to
      reduce problems arising at the interface between primary and secondary care. The
      aim is to compare the willingness of hospital specialists and general
      practitioners to use joint treatment guidelines, and to determine the most
      relevant barriers and facilitators. STUDY DESIGN: A structured survey, consisting
      of questions about the use of guidelines and formularies in general, and possible
      barriers and facilitators for using a specific joint guideline. These specific
      guidelines concerned the treatment of hypertension, heart failure, or diabetes
      mellitus. SETTING AND STUDY PARTICIPANTS: One hundred and ninety-seven general
      practitioners and 34 general internists and cardiologists from the north of the
      Netherlands. RESULTS: Most hospital specialists relied for their prescribing on
      international guidelines and agreements within their own department, while
      general practitioners relied more on national and regional guidelines. General
      practitioners were more supportive than specialists of the initiative to develop
      joint treatment guidelines, although both groups had concerns regarding the
      development process. An important barrier for specialists was that they did not
      perceive a need for these guidelines. As enabling factors, physicians stated that
      these joint guidelines can lead to harmonization between specialists and general
      practitioners, and that they can be useful as an educational tool. CONCLUSION:
      Specialists are less ready to adopt joint treatment guidelines than general
      practitioners, indicating the need for a different approach to implement such
      guidelines in the two sectors.

PMID- 15150155
TI  - Home care aides in the administration of medication.
AB  - OBJECTIVE: To assess to what extent home care aides (HCAs) within the social
      services are engaged in medication administration, including their knowledge of
      how to perform this work correctly, and also to assess their knowledge of
      pharmacology, adverse drug effects, diseases, and symptoms. Furthermore, we
      wanted to study if there were any changes to be seen in these areas since a
      previous study. DESIGN: A repeated survey, carried out in 1998, 5 years after a
      cross-sectional study. In a stratified sample of personnel within the social
      services in nine of Malmo's (Sweden) 10 administrative districts, a questionnaire
      with multiple-choice and open-ended questions was answered individually and under
      supervision. Statistical analyses were carried out using the chi-square test,
      except for logistic regression where odds-ratios were presented. STUDY
      PARTICIPANTS: Employees (341) within the social services in the municipality of
      Malmo, of whom 313 were HCAs and 28 were supervisors, most of whom also were
      HCAs, at a total of 36 workplaces. The study 5 years earlier included 393
      employees, of whom 39 were supervisors and 354 were HCAs. MAIN OUTCOME MEASURES:
      Where possible, the answers in the knowledge test were classified as 'correct',
      'partially correct' or 'erroneous', or were assigned to the group 'do not
      know/have not answered'. RESULTS: Most (95%) of the HCAs were engaged in
      medication administration. On average, 53% managed to give a correct or partially
      correct answer on questions concerning medication administration. The result
      concerning indications for common drugs was 55%, contra-indications and adverse
      drug effects 25%, and symptoms 59%. Some general improvements in knowledge were
      seen from 1993 to 1998, mostly in the area of medication administration, but the
      results also indicated a change for the worse in the area of indications for
      common drugs. CONCLUSIONS: Although most HCAs are engaged in medication
      administration, to a great extent they lack knowledge in the area. There is a
      need for additional personnel with the appropriate professional background, i.e.
      registered nurses, and a need for further training of HCAs in order to ensure
      patient safety. With respect to this, issues of learning and quality improvement
      are discussed.

PMID- 15150157
TI  - The progress of reforms: job satisfaction in a typical hospital in Estonia.
AB  - OBJECTIVE: To evaluate the level of job satisfaction among the staff at an
      Estonian hospital and to describe factors related to their job satisfaction.
      DESIGN: Questionnaire survey. SETTING: Parnu County Hospital in Estonia. STUDY
      PARTICIPANTS: All staff members of the Parnu County Hospital (n = 673), except 56
      staff members who were away from work during the study. RESULTS: Respondents (n =
      473) indicated an average job satisfaction level of 3.86 +/- 0.81 on a 5-point
      scale. The efficiency of hospital management as measured by planning,
      relationships with supervisors, knowledge and communication regarding hospital
      goals, plans, quality of services, budgetary situation, and staffing problems was
      positively correlated with job satisfaction. Stress and unrealistic expectations
      were negatively correlated with job satisfaction. The feeling of being part of
      the organization was also correlated with job satisfaction. Recognition from
      supervisors and discussions with colleagues were found to be weakly correlated
      with job satisfaction. There were differences between occupational categories.
      CONCLUSION: The management of Parnu County Hospital has been able to create good
      supervisory relationships with staff by providing sufficient information about
      the goals of the hospital, the quality of services, the budgetary situation, and
      staffing problems that arise. Stress levels reported are not excessive and staff
      are loyal to their hospital.

PMID- 15150156
TI  - Physician knowledge and adherence to prescribing antibiotic prophylaxis for
      sickle cell disease.
AB  - OBJECTIVE: The purpose of this research was to examine how physician
      characteristics were associated with: (i). physician knowledge of and adherence
      to sickle cell guidelines; and (ii). the types of educational programs about
      sickle cell disease desired by physicians. METHODS: A survey was developed to
      assess the research objective. After the survey was pre-tested and an
      institutional review board exemption was obtained, it was sent to a systematic
      random sample of 375 pediatricians and all 125 practicing hematologists in North
      Carolina. They were asked to answer a six-item knowledge test relating to the
      antibiotic prophylaxis guidelines. RESULTS: The response rate was 57%, of which
      61% were pediatricians. Over half (56%) were in a practice with at least one
      pediatric sickle cell patient. Fifty-nine percent of physicians answered five or
      more questions correctly on the knowledge test. The question most physicians
      answered correctly (97%) pertained to the necessity of antibiotics for children
      with sickle cell disease. The question most frequently answered incorrectly (62%)
      pertained to prescribing antibiotics to a child with unconfirmed sickle cell
      disease. Logistic regression results indicated that the number of sickle cell
      patients seen in practice influenced the number of questions answered correctly.
      Sixty-six percent of physicians prescribed prophylactic antibiotics for 100% of
      their patients with sickle cell disease and therefore were 100% adherent. Eighty
      one percent of pediatricians compared with 12% of hematologists were 100%
      adherent in prescribing antibiotics. Hematologists and those practicing at a
      medical school or university were less likely to be 100% adherent in prescribing
      antibiotic prophylaxis. CONCLUSION: The majority of physicians surveyed were
      relatively knowledgeable about sickle cell guidelines, however there may be a
      need for continuing education programs that focus on the issues of prescribing
      antibiotics to a child with unconfirmed sickle cell disease and penicillin
      dosage.

PMID- 15150158
TI  - There is nothing wrong with the concept of a root cause.

PMID- 15150159
TI  - Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the
      ciliary ganglion: mechanistic insights into human congenital central
      hypoventilation syndrome.
AB  - Dilp1 is a semi-dominant mouse mutation that causes dilated pupils when
      heterozygous and is lethal when homozygous. We report here that it is caused by a
      point mutation that introduces a stop codon close to the start of the coding
      sequence of the paired-like homeobox transcription factor Phox2b. Mice carrying a
      targeted allele of Phox2b also have dilated pupils and the two alleles do not
      complement. Phox2b is necessary for the development of the autonomic nervous
      system and when absent one of the consequences is that all parasympathetic
      ganglia fail to form. Constriction of the pupil is a parasympathetic response
      mediated by the ciliary ganglion and we find that in Phox2b heterozygous mutants
      it is highly atrophic. The development of other parasympathetic and sympathetic
      ganglia appears to be largely unaffected indicating that the ciliary ganglion is
      exquisitely sensitive to a reduction in dose of this transcription factor. PHOX2B
      has been implicated in human disease. Mutations, principally leading to
      polyalanine expansions within the protein, have been found in patients with
      congenital central hypoventilation syndrome (CCHS), the cardinal feature of which
      is an inability to breathe unassisted when asleep. Additionally, some CCHS
      patients have ocular abnormalities, including pupillary defects, although they
      principally have constricted rather than dilated pupils. The apparent phenotypic
      differences observed between mice carrying a loss-of-function mutation of Phox2b
      and CCHS patients indicate that PHOX2B mutations found in CCHS patients, all of
      which can produce proteins with intact DNA-binding domains, are gain-of-function
      mutations that alter rather than abolish protein function.

PMID- 15150160
TI  - The unique transcriptome through day 3 of human preimplantation development.
AB  - Successful human development is dependent upon a cascade of events following
      fertilization. Unfortunately, knowledge of these critical events in humans is
      remarkably incomplete. Although hundreds of thousands of human embryos are
      cultured yearly at infertility centers worldwide, the vast majority fail to
      develop in culture or following transfer to the uterus. In this study, we sought
      to characterize global patterns of gene expression in individual, normal embryos
      during the first three days of embryonic life using microarrays; we then compared
      gene expression between normally growing and growth-arrested embryos using
      quantitative PCR. Our results documented several novel findings. First, we found
      that a complex pattern of gene expression exists; most genes that are
      transcriptionally modulated during the first three days following fertilization
      are not upregulated, as was previously thought, but are downregulated. Second, we
      observed that the majority of genes exhibiting differential expression during
      preimplantation development are of unknown identity and/or function. Third, we
      show that embryonic transcriptional programs are clearly established by day 3
      following fertilization, even in embryos that arrested prematurely with 2-, 3- or
      4-cells. This indicates that failure to activate transcription is not associated
      with the majority of human preimplantation embryo loss. Finally, taken together,
      these results provide the first global analysis of the human preimplantation
      embryo transcriptome, and demonstrate that RNA can be amplified from single
      oocytes and embryos for analysis by cDNA microarray technology, thus lending
      credence to additional studies of genetic regulation in these cell types, as well
      as in other small biological samples.

PMID- 15150162
TI  - Normal telomere erosion rates at the single cell level in Werner syndrome
      fibroblast cells.
AB  - The aim of this study was to investigate whether the accelerated replicative
      senescence seen in Werner syndrome (WS) fibroblasts is due to accelerated
      telomere loss per cell division. Using single telomere length analysis (STELA) we
      show that the mean rate of telomere shortening in WS bulk cultures ranges between
      that of normal fibroblasts [99 bp/population doubling (PD)] and four times that
      of normal (355 bp/PD). The telomere erosion rate in the fastest eroding strain
      slows in the later stages of culture to that observed in normal fibroblasts, and
      appears to be correlated with a reduction in the heterogeneity of the telomere
      length distributions. Telomere erosion rates in clones of WS cells are much
      reduced compared with bulk cultures, as are the variances of the telomere-length
      distributions. The overall lack of length heterogeneity and the normal erosion
      rates of the clonal populations are consistent with simple end-replication losses
      as the major contributor to telomere erosion in WS cells. We propose that
      telomere dynamics at the single cell level in WS fibroblasts are not
      significantly different from those in normal fibroblasts, and suggest that the
      accelerated replicative decline seen in WS fibroblasts does not result from
      accelerated telomere erosion.

PMID- 15150161
TI  - Disorder-associated mutations lead to functional inactivation of neuroligins.
AB  - Autism is a neuro-developmental syndrome that affects 0.1-0.5% of the population.
      It has been proposed that alterations in neuronal circuitry and/or neuronal
      signaling are responsible for the behavioral and cognitive aberrations in autism
      patients. However, the cellular basis of such alterations is unknown. Recently,
      point mutations in a family of neuronal cell adhesion molecules called
      neuroligins have been linked to autism-spectrum disorders and mental retardation.
      We investigated the consequences of these disease-associated mutations on
      neuroligin function. We demonstrate that the point mutation at arginine 451 and a
      nonsense mutation at aspartate 396 of neuroligin-3 and -4 (NL3 and NL4),
      respectively, result in intracellular retention of the mutant proteins. Over
      expression of wild-type NL3 and NL4 proteins in hippocampal neurons stimulates
      the formation of presynaptic terminals, whereas the disease-associated mutations
      result in a loss of this synaptic function. Our findings suggest that the
      previously identified mutations in neuroligin genes are likely to be relevant for
      the neuro-developmental defects in autism-spectrum disorders and mental
      retardation since they impair the function of a synaptic cell adhesion molecule.

PMID- 15150163
TI  - Detection of elements of the staphylococcal cassette chromosome (SCC) in a
      methicillin-susceptible (mecA gene negative) homologue of a fucidin-resistant
      MRSA.
AB  - OBJECTIVES: To determine the DNA relatedness of an outbreak of community-acquired
      fucidin-resistant methicillin-resistant Staphylococcus aureus (MRSA) and
      methicillin-susceptible S. aureus (MSSA) isolated from intravenous drug users
      (IVDUs). MATERIALS AND METHODS: Relatedness was determined by PFGE analysis of
      macro-restricted chromosome, together with a variety of PCR methods, to determine
      polymorphisms in the accessory gene regulator (agr) locus, the structure of the
      staphylococcal cassette chromosome (SCCmec) and the presence or absence of the
      gene encoding Panton-Valentine leucocidin (PVL). RESULTS: Clonality of the MRSA
      and MSSA was established by PFGE, a finding further supported by agr analysis. By
      PCR, the MRSA contained the typical genetic organization of SCCmec type-1.
      However, the MSSA, though mecA-negative, contained certain fragments of the SCC.
      Genes encoding PVL were not detected. CONCLUSIONS: This outbreak involved a
      community-acquired fucidin-resistant MRSA and its methicillin-susceptible
      homologue. The MSSA did not contain the mecA gene but did contain elements of the
      mobile type-I SCC. The MSSA were associated with a change in PFGE pattern with a
      deletion in fragment size of approximately 215-195 kb.

PMID- 15150164
TI  - Relationship between ceftriaxone use and resistance to third-generation
      cephalosporins among clinical strains of Enterobacter cloacae.
AB  - OBJECTIVE: To investigate the potential correlation between the use of extended
      spectrum cephalosporins (ESCs) and resistance to this antibiotic class among
      clinical isolates of Enterobacter cloacae in a university-affiliated hospital.
      MATERIALS AND METHODS: Data on antimicrobial resistance and antimicrobial use
      concerning E. cloacae and ESCs were collected over a 4 year period. Various
      statistical tools were used to explore the potential relationship. RESULTS: From
      1999 to 2002, the proportion of E. cloacae isolates resistant to ESCs increased
      from 24.3% to 29.6%. (P=0.04), and the quantity of ESCs prescribed and given did
      not change. Within the subclass constituted by first-line ESCs, the proportion of
      ceftriaxone increased from 64.3% to 77.6% and the proportion of cefotaxime
      decreased accordingly, from 35.7% to 22.4%. Statistical analyses showed that E.
      cloacae resistance to ESCs correlated with ceftriaxone use regardless of the
      other ESCs. For every defined daily dose of ceftriaxone per 1000 patient days
      used in our hospital, resistance of E. cloacae isolates to ESCs increased by
      1.36%. CONCLUSION: This study demonstrates a specific correlation between
      ceftriaxone use and the development of resistance in E. cloacae clinical
      isolates. The high biliary elimination of ceftriaxone compared with other ESCs
      may be responsible for a greater impact of this antibiotic on the digestive
      flora.

PMID- 15150165
TI  - Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti
      amoebic agents.
AB  - OBJECTIVES: The current use of metronidazole as an anti-amoebic agent causes
      significant side-effects. The purpose of this study was to identify alternative
      compounds with which to treat amoebiasis. METHODS: We tested the effects of
      cyclopropyl (CPC) and cyclobutyl (CBC) carbinols on the survival of Entamoeba
      histolytica trophozoites and on the enzymatic activities of E. histolytica
      alcohol dehydrogenase 2 (EhADH2), a crucial enzyme in the amoebic fermentation
      pathway. RESULTS: At 72 h, the estimated 50% inhibitory concentrations of CPC and
      CBC were 38.9 and 11.2 microM, respectively. The EhADH2 alcohol and aldehyde
      dehydrogenase activities were inhibited by 1.82 microM CPC and 0.89 microM CBC in
      vitro. CONCLUSIONS: CPC and CBC are expected to be non-toxic to humans at the
      concentrations required to eliminate E. histolytica trophozoites. Similarities
      between EhADH2 and the Giardia lamblia AdhE enzyme indicate that CPC and CBC
      could be effective drugs for treatment of both amoebiasis and giardiasis.

PMID- 15150166
TI  - A 6 day course of liposomal amphotericin B in the treatment of infantile visceral
      leishmaniasis: the Italian experience.
AB  - OBJECTIVES: To evaluate in a retrospective analysis the efficacy and safety of a
      6 day course of liposomal amphotericin B (L-AmB) in infantile cases of
      Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in
      Italy. PATIENTS AND METHODS: Patients included were diagnosed as having VL
      consecutively admitted from December 1992 to December 2001 at four main referral
      children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L
      AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data,
      nutritional status, underlying diseases, clinical and laboratory findings, and
      therapy outcome were considered. RESULTS: A total of 164 HIV-negative children
      (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients
      were initially cured by the given treatment, and did not present adverse events
      related to drug infusion. Seven patients (4.3%) had a clinical and
      parasitological relapse 3-15 months after therapy. All relapses were successfully
      retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg).
      CONCLUSIONS: This study highlights the efficacy (>95%) and safety of the six dose
      L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in
      children.

PMID- 15150167
TI  - Assessment of a microplate method for determining the post-antibiotic effect in
      Staphylococcus aureus and Escherichia coli.
AB  - OBJECTIVES: The post-antibiotic effect (PAE) is an important parameter of
      antibiotic action that is widely used as a predictor of pharmacodynamic activity.
      Traditionally, PAE has been determined by a labour-intensive method involving
      determination of viable cell numbers. New methods using spectrophotometric
      procedures could offer significant advantages for PAE determinations,
      particularly in terms of speed. A number of such methods have been described in
      the literature, but extensive comparison with the classical procedure for
      determining PAEs has not been carried out. We have now compared PAE values
      obtained using a rapid microplate method with those achieved by the classical
      viable count procedure. METHODS: We determined PAE values for a variety of
      antibiotics against Staphylococcus aureus and Escherichia coli following exposure
      to 5 x MIC drug concentrations for 60 min in Mueller-Hinton Broth (MHB). The
      duration of the PAE was obtained by following the recovery of bacterial growth in
      antibiotic-free MHB measured either as colony forming units on Mueller-Hinton
      agar, or as culture absorbance (600 nm) in a microplate reader. RESULTS: For
      bacteriolytic agents there was poor correlation between the two methods for both
      S. aureus (R2=0.096) and E. coli (R2=0.5456). However, when PAEs for
      bacteriostatic agents and non-lytic bactericidal agents were compared,
      correlation between the two methods was high for both S. aureus (R2=0.7529) and
      E. coli (R2=0.7687). CONCLUSIONS: The spectrophotometric microplate method for
      determining PAEs may be a suitable alternative to the classical method for those
      antibiotics that do not induce bacterial cell lysis.

PMID- 15150169
TI  - Molecular characterization of penicillin non-susceptible Streptococcus pneumoniae
      in Christchurch, New Zealand.
AB  - OBJECTIVES: To determine the epidemiological relationship between non-invasive
      penicillin non-susceptible Streptococcus pneumoniae isolates collected in the
      Christchurch community between 1997 and 2001. METHODS: One hundred and ninety
      seven pneumococcal isolates were examined by macrorestriction profile analysis of
      SmaI-digested genomic DNA separated by PFGE and restriction fragment length
      polymorphism analysis of penicillin binding protein genes. RESULTS: Four major
      clonal lineages were identified, the largest and most homogeneous containing 95
      (48.2%) of the isolates, the bulk of which (93.7%), had identical
      macrorestriction patterns. Members of this clonal group were multidrug-resistant
      and exhibited high resistance to third-generation cephalosporins, with MICs > or
      =8.0 mg/L not uncommon (23.1%). Two of the clonal groups, each containing 24
      (12.2%) isolates, appeared indistinguishable from the globally widespread
      Spain23F-1 and France9V-3 strains, respectively. The fourth (12.7% of isolates)
      multidrug-resistant clone possessed intermediate penicillin susceptibility (MIC
      0.12 mg/L). CONCLUSIONS: This study shows that several distinct penicillin
      resistant pneumococcal clones are present in the Christchurch community, most of
      which appear to have been imported into New Zealand.

PMID- 15150168
TI  - Evaluation of a new cefepime-clavulanate ESBL Etest to detect extended-spectrum
      beta-lactamases in an Enterobacteriaceae strain collection.
AB  - OBJECTIVES: In this study, we evaluated the performance of a new ESBL Etest
      configuration based on clavulanate synergy with cefepime compared with cefotaxime
      clavulanate and ceftazidime-clavulanate ESBL Etest strips for the detection of
      extended-spectrum beta-lactamases (ESBL) in an Enterobacteriaceae strain
      collection, with special focus on Enterobacter spp. METHODS: Overall, a total of
      54 clinical isolates of ESBL-producing Enterobacteriaceae species were evaluated:
      Enterobacter aerogenes (n=3), Enterobacter cloacae (n=10), Escherichia coli
      (n=10), Klebsiella oxytoca (n=3), Klebsiella pneumoniae (n=25) and Proteus
      mirabilis (n=3). To check Etest behaviour with resistance phenotypes similar to
      ESBL, our panel was expanded by six clinical isolates of K. oxytoca that were
      identified as putative producers of their chromosomal K1 beta-lactamase. RESULTS:
      With this panel, ESBL Etest was 98% sensitive with cefepime-clavulanate, 83% with
      cefotaxime-clavulanate, and 74% with ceftazidime-clavulanate strips.
      Concentrating on Enterobacter spp., reliable ESBL detection could only be
      achieved by the new cefepime-clavulanate strip since it confirmed ESBL production
      in all strains (100% sensitivity) whereas only 4/13 (31%) of Enterobacter strains
      were positive using cefotaxime-clavulanate or ceftazidime-clavulanate strips. A
      limitation of using the new cefepime strip was less than optimal specificity with
      K1 phenotypes of K. oxytoca: among six strains, four isolates were scored false
      positive by Etest strips containing cefepime-clavulanate. CONCLUSION: The new
      Etest ESBL strip containing cefepime-clavulanate is a valuable supplement to
      current methods for detection of ESBLs. In our study collection, the cefepime
      clavulanate strip was the best configuration for detection of ESBLs, particularly
      in Enterobacter spp.

PMID- 15150170
TI  - Nitroimidazole resistance genes (nimB) in anaerobic Gram-positive cocci
      (previously Peptostreptococcus spp.).
AB  - OBJECTIVES: To investigate metronidazole resistance and the prevalence of
      nitroimidazole (nim) genes in clinically isolated anaerobic Gram-positive cocci.
      METHODS: Metronidazole susceptibility was determined in 99 strains of anaerobic
      Gram-positive cocci and PCR amplification for the nim gene carried out on 61
      strains (metronidazole MIC > or =0.5 mg/L). RESULTS: The nimB gene was detected
      in 34% (21/61) of the strains. These included two highly resistant Finegoldia
      magna strains (MICs >128 mg/L). The nimB gene was, however, also demonstrated in
      90% (19/21) of susceptible strains. CONCLUSIONS: Although the nimB gene may be
      implicated in the high-level metronidazole resistance in 2 F. magna strains, the
      alarmingly high prevalence of the nimB gene in anaerobic Gram-positive cocci
      cannot be directly associated with resistance and the possibility of a silent
      nimB gene should be considered.

PMID- 15150171
TI  - Pharmacokinetic basis for the use of extended interval dosage regimens of
      gentamicin in neonates.
AB  - OBJECTIVES: To analyse the pharmacokinetic basis for the use of extended-interval
      dosage regimens of gentamicin in neonates using population pharmacokinetics.
      PATIENTS AND METHODS: The population pharmacokinetics of gentamicin was studied
      retrospectively in a population of 113 neonates divided into two groups: one for
      computing the population model (n=97) and another for validation (n=36). A one
      compartment pharmacokinetic model and non-linear mixed-effects modelling were
      used to assess the population pharmacokinetic model. RESULTS: Weight (W) and
      postnatal age (PA) were the covariates that influenced the pharmacokinetic
      parameters of gentamicin. The final population model obtained was: distribution
      volume, V (L)=0.636 x W (kg)0.852; clearance, Cl (L/h)=0.032 x W (kg)1.482+0.0024
      x PA (days). The predictive performance of the model in the population validation
      was adequate for clinical purposes. The optimized population model allowed us to
      simulate gentamicin serum levels and their variability, in this kind of patient,
      when extended-interval dosage administration regimens were implemented.
      CONCLUSIONS: According to our pharmacokinetic population model, initial doses of
      gentamicin of 10 mg/kg, and dosage intervals between 36-48 h, appear to be
      appropriate to achieve target peak and trough serum levels of 15-20 and <0.5
      mg/L, respectively, when extended-interval dosage regimens are implemented in
      newborns. The half-life of gentamicin in premature babies of very low weight and
      gestational age <31 weeks is long. Thus, to achieve serum concentrations in the 1
      10 mg/L range, the use of dosage regimens of 5 mg/kg at 36-48 h dosage intervals
      seems suitable.

PMID- 15150172
TI  - Influence of protein binding under controlled conditions on the bactericidal
      activity of daptomycin in an in vitro pharmacodynamic model.
AB  - OBJECTIVE: Daptomycin exhibits bactericidal activity against clinically
      significant Gram-positive bacteria despite being highly bound to human proteins.
      Evaluations characterizing the effect of protein on daptomycin pharmacodynamics
      are warranted. METHODS: We utilized an in vitro pharmacodynamic model to simulate
      daptomycin regimens of 6 mg/kg/day under controlled conditions of pH, calcium
      and/or protein. Free concentrations were simulated in broth, whereas total
      concentrations were simulated in broth supplemented with human albumin. Bacterial
      density was profiled over 48 h for two methicillin-resistant Staphylococcus
      aureus (MRSA) and two vancomycin-resistant Enterococcus faecium (VREF) clinical
      isolates. RESULTS: Daptomycin exhibited bactericidal activity against both MRSA
      isolates, with time to 99.9% killing occurring at 0.5 h and 8 h in broth and in
      albumin-supplemented broth, respectively. Initial kill was observed against both
      VREF isolates followed by regrowth. There was no statistical difference (P>0.05)
      in extent of bacterial kill at 24 or 48 h between the different media.
      CONCLUSIONS: Although delayed, the extent of kill for daptomycin was unaltered
      against all isolates in albumin-supplemented broth. Further antimicrobial studies
      that incorporate protein are warranted to assess the influence of protein in the
      pharmacodynamic evaluation of antimicrobials.

PMID- 15150173
TI  - Differential gene expression in a Bacteroides fragilis metronidazole-resistant
      mutant.
AB  - OBJECTIVES: The current work focused on molecular changes in a spontaneous
      Bacteroides fragilismutant selected by low concentrations of metronidazole as an
      adaptive response to the drug. METHODS: A metronidazole-resistant strain derived
      from B. fragilis ATCC 25285 was selected by passage in the presence of drug using
      0-4 mg/L gradient plates. Using a combination of proteomics for identification of
      differentially expressed proteins by two-dimensional electrophoresis and selected
      mutational analyses by single cross-over insertion and an allelic exchange, we
      have identified genes involved in the adaptive response to metronidazole.
      RESULTS: There are significant changes in the protein profiles of resistant
      strains. These changes appeared to affect a wide range of metabolic proteins
      including lactate dehydrogenase (up-regulated) and flavodoxin (down-regulated),
      which may be involved in electron transfer reactions. Also, the enzymic activity
      of the pyruvate-ferredoxin oxidoreductase (PorA) complex was impaired. Mutant
      strains lacking the genes for flavodoxin and PorA were less susceptible to
      metronidazole than the sensitive parent, and a double flavodoxin/PorA mutant had
      even less susceptibility but none of the mutants were as resistant as the
      spontaneous metronidazole-resistant strain. CONCLUSIONS: Overall, the data
      indicated that there were global changes in the regulation of the physiology of
      the metronidazole-resistant strain. In addition, flavodoxin was identified as an
      important contributor to metronidazole sensitivity in B. fragilis.

PMID- 15150174
TI  - Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in
      healthy volunteers.
AB  - OBJECTIVES: To investigate different dose combinations of amprenavir and
      delavirdine in order to assess an optimal dose suitable for clinical use.
      METHODS: This was a prospective, open-label, controlled, three-period, multiple
      dose study with nine healthy volunteers. The volunteers received three different
      dose combinations of amprenavir and delavirdine twice a day for 10 days with a
      subsequent 12 h pharmacokinetic evaluation. Combination 1: amprenavir 600 mg and
      delavirdine 600 mg; combination 2: amprenavir 600 mg and delavirdine 800 mg;
      combination 3: amprenavir 450 mg and delavirdine 1000 mg. The combinations were
      taken at least 2 weeks apart. RESULTS: Differences in median delavirdine Cmax,
      C12 and AUC0-12 were seen when comparing the three combinations (3 > 2>1)
      (P<0.04). A considerable and clinically important higher median C12 was seen with
      combination 3 when compared to combination 1 (835 to 3944 ng/mL) (P=0.0039). Only
      small differences in the amprenavir pharmacokinetic parameters were seen between
      the three dose combinations, with a median C12 of 412, 434 and 536 ng/mL,
      respectively. CONCLUSIONS: In this study, an increase of 472% in median
      delavirdine C12 was seen with a delavirdine dose increase of only 67% (600 to
      1000 mg). Saturation of the CYP3A4 enzymes and/or possibly also P-glycoprotein
      could be involved. Combination 3 was considered most suitable for clinical use,
      but because of the large inter-individual variation in steady-state
      concentrations, the use of the combination should be supported by therapeutic
      drug monitoring and restricted to certain patients.

PMID- 15150175
TI  - Trends in antimicrobial resistance, phage types and integrons among Salmonella
      serotypes from pigs, 1997-2000.
AB  - OBJECTIVES: The objectives of this study were to determine antimicrobial
      resistance and to identify phage types and class 1 integrons among non-typhoidal
      Salmonella isolates from 24 pig farms in North Carolina collected between 1997
      and 2000. METHODS: A total of 1314 isolates of 30 serotypes from pig faecal
      samples were collected and analysed over a 3 year period. The isolates were
      characterized using antimicrobial susceptibility testing, phage typing, PCR and
      DNA sequencing for class 1 integrons. RESULTS: A high frequency of resistance to
      antimicrobial agents including tetracycline (85%), ampicillin (47%), co-amoxiclav
      (23%) and chloramphenicol (21%) was detected. Two multidrug resistance patterns
      were common in Typhimurium (including variant Copenhagen): isolates with co
      amoxiclav, ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and
      tetracycline (R-type AxACSSuT) [36%] and isolates with ampicillin, kanamycin,
      streptomycin, sulfamethoxazole and tetracycline (R-type AKSSuT) [45%] resistance
      patterns. Definitive Type 104 (DT104) was the most common (34%) among eight phage
      types identified. AKSSuT was found among non-DT104 phage types, particularly DT21
      and DT193. Class 1 integrons were detected among various serotypes including
      Typhimurium, Derby, Muenchen, Worthington, Bere and Muenster. aadA was the most
      common resistance gene insert, and the oxa30 beta-lactamase resistance gene was
      also identified among serovar Muenchen. CONCLUSIONS: In this study, two most
      important multidrug resistance patterns (AxACSSuT and AKSSuT) and phage types of
      public health significance (DT104 and DT193) constituted two-thirds of the
      serotype Typhimurium isolates. The findings imply that pigs raised in the
      commercial production system may pose a risk in serving as reservoirs of
      resistant Salmonella.

PMID- 15150176
TI  - Characterization of the first CTX-M-14-producing Salmonella enterica serotype
      Enteritidis isolate.

PMID- 15150177
TI  - Role for malonyl coenzyme A:acyl carrier protein transacylase (MCAT) in the
      growth-inhibitory effect of the calmodulin antagonist trifluoperazine in
      Mycobacterium bovis BCG.
AB  - OBJECTIVES: To determine whether the fatty acid synthesis enzyme malonyl coenzyme
      A:acyl carrier protein transacylase (MCAT) is involved in the growth-inhibitory
      effect of trifluoperazine in the tubercle bacillus Mycobacterium bovis BCG.
      METHODS: BCG was grown in liquid culture with various concentrations of
      trifluoperazine and growth was monitored by OD measurement. To determine the
      effect of trifluoperazine on MCAT protein level, total protein was extracted from
      BCG cultures and was analysed by 2D gel electrophoresis and western blot. To
      confirm trifluoperazine-dependent reduction in the MCAT protein level, two BCG
      strains overexpressing MCAT at a low and high constitutive level were similarly
      tested. The synergic effect of trifluoperazine and isoniazid was tested at sub
      MIC levels in liquid cultures. RESULTS: Trifluoperazine inhibition of growth
      correlates with reduction in the steady-state level of MCAT protein.
      Overexpression of MCAT confers resistance to trifluoperazine. Trifluoperazine
      acts synergically (albeit weakly) with isoniazid and no resistance towards
      isoniazid alone was observed due to overexpression of MCAT. This suggests MCAT to
      be a specific target of trifluoperazine. CONCLUSION: These results indicate MCAT
      as a target of trifluoperazine and provide an explanation for the inhibitory
      effect of trifluoperazine on mycobacterial lipid synthesis observed earlier. This
      makes MCAT a potential target for new antimycobacterials.

PMID- 15150178
TI  - Ertapenem: a Group 1 carbapenem with distinct antibacterial and pharmacological
      properties.
AB  - Ertapenem, a Group 1 carbapenem, is the most recent beta-lactam antibiotic to
      enter clinical practice in the USA and Europe. While structurally a carbapenem,
      the overall molecular structure of ertapenem has been modified to focus its
      antibacterial spectrum on important community-acquired aerobic and anaerobic
      pathogens, and to increase its plasma half-life, permitting once-a-day dosing for
      this parenteral antibiotic. A number of chemical features are responsible for the
      unique properties of ertapenem. The inclusion of a trans-1-hydroxyethyl group in
      the structure of ertapenem enables the drug to maintain antibacterial efficacy
      against the vast majority of beta-lactamase-producing organisms. A critical 1beta
      methyl substituent shields the beta-lactam carbonyl group and serves to reduce
      dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling
      ertapenem to be administered without a DHP-1 inhibitor. A meta-substituted
      benzoic acid substituent increases the molecular weight and lipophilicity of the
      molecule, and the carboxylic acid moiety, ionized at physiological pH, results in
      ertapenem having a net negative charge. As a result, ertapenem is highly protein
      bound and has an extended half-life, permitting a once-a-day treatment regimen.

PMID- 15150179
TI  - In vitro activity of ertapenem: review of recent studies.
AB  - Ertapenem is a long-acting, 1beta-methyl parenteral Group 1 carbapenem antibiotic
      that has a broad antibacterial spectrum and once-a-day dosing supported by
      clinical studies. Ertapenem is active against both Gram-positive and Gram
      negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and
      most species of anaerobic bacteria. Isolates from a variety of infections (intra
      abdominal infections, skin/soft-tissue infections, community-acquired pneumonia,
      pelvic infections and urinary tract infections) are inhibited by ertapenem. It
      has restricted activity against nosocomial pathogens such as Pseudomonas
      aeruginosa, Acinetobacter species, methicillin-resistant staphylococci and
      enterococci. Ertapenem has potent activity against the majority of anaerobic
      isolates from intra-abdominal infections, and against most of the aerobes
      isolated from these infections, with the exceptions of the nosocomial pathogens
      mentioned above. MIC(90)s for most species of Enterobacteriaceae were <1 mg/L,
      significantly lower than those of imipenem. MIC(90)s for most Bacteroides
      fragilis group isolates ranged from 1 to 4 mg/L, and MIC(90)s were species
      specific for Clostridium, ranging from 0.06 mg/L for Clostridium perfringens to 4
      mg/L for Clostridium clostridioforme. Ertapenem was equivalent to or better than
      piperacillin-tazobactam in activity against most anaerobic species isolated from
      these infections, and was more potent than piperacillin-tazobactam and
      ceftriaxone against the most common skin pathogens (e.g. methicillin-susceptible
      Staphylococcus aureus). Ertapenem was highly active against most of the pathogens
      isolated from patients with community-acquired pneumonia, except for isolates of
      methicillin-resistant S. aureus (which are infrequent causes of community
      acquired infection); these isolates were also resistant to ceftriaxone.
      Resistance to ertapenem is most commonly attributable to a variety of mechanisms
      including alterations in penicillin-binding proteins in Gram-positive organisms,
      and combinations of potent metallo-beta-lactamase enzymes, porin protein defects
      and efflux pumps in Gram-negative organisms.

PMID- 15150180
TI  - Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians.
AB  - Ertapenem, a Group 1 carbapenem, is a once-a-day parenteral beta-lactam
      antibiotic recently licensed in the USA and Europe. Monotherapy with ertapenem
      dosed as 1 g once a day has been shown to be highly effective in clinical trials
      for the treatment of complicated infections of skin and skin structures,
      complicated intra-abdominal infections, community-acquired pneumonia, acute
      pelvic infections and complicated urinary tract infections. Dosing modifications
      have not been recommended for adults on the basis of gender, age, weight or liver
      disease. Presently there are no data regarding the use of ertapenem in children.
      Dose reductions are indicated for patients with advanced renal insufficiency.
      Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome
      P450 enzymes; significant drug interactions between ertapenem and drugs handled
      by these systems are not expected.

PMID- 15150181
TI  - Intra-abdominal infections: review of the bacteriology, antimicrobial
      susceptibility and the role of ertapenem in their therapy.
AB  - Complicated intra-abdominal infections require a combination of surgery/drainage
      and antimicrobial therapy that is active against both the aerobic and the
      anaerobic bacteria that comprise the intestinal flora. Ertapenem, a parenteral
      carbapenem, is highly resistant to a wide variety of beta-lactamase enzymes, and
      has a broad spectrum of activity against bacteria associated with community
      acquired infections including those of complicated intra-abdominal conditions.
      This article reviews the bacteriology of complicated intra-abdominal infections,
      their antimicrobial susceptibility, especially to anaerobes, the utility of
      animal models in these mixed infections, and the supportive clinical trials and
      in vitro susceptibility data that show ertapenem to be generally well tolerated
      and as effective as either piperacillin-tazobactam or ceftriaxone plus
      metronidazole in the therapy of complicated intra-abdominal infections.

PMID- 15150182
TI  - Complicated infections of skin and skin structures: when the infection is more
      than skin deep.
AB  - Skin and skin-structure infections are common, and range from minor pyodermas to
      severe necrotizing infections. Complicated infections are defined as involving
      abnormal skin or wounds, occurring in compromised hosts, or requiring surgical
      intervention. Classification schemes for these infections are varied and
      confusing. Distinguishing characteristics include the aetiological agent(s),
      clinical context and findings, depth of tissue involvement and rate of
      progression. The most common pathogens are aerobic Gram-positive cocci, but
      complicated infections frequently involve Gram-negative bacilli and anaerobic
      bacteria. Initial antibiotic therapy is usually empirical, and later modified by
      the results of stains and cultures of wound specimens. Broad-spectrum coverage is
      frequently needed for complicated infections. Ertapenem is a once-a-day
      parenteral Group 1 carbapenem antibiotic, recently licensed in the USA and
      Europe, which may assume an important role in treating some complicated skin and
      skin-structure infections. Surgical debridement is important for many complicated
      infections, and is the critical element in managing necrotizing fasciitis and
      myonecrosis.

PMID- 15150183
TI  - Treatment of polymicrobial infections: post hoc analysis of three trials
      comparing ertapenem and piperacillin-tazobactam.
AB  - The efficacy of ertapenem 1 g once a day for the treatment of polymicrobial
      complicated intra-abdominal, complicated skin/skin-structure and acute pelvic
      infections was compared with piperacillin-tazobactam 3.375 g every 6 h in a post
      hoc analysis of data from three large randomized double-blind trials. Of the
      1,558 treated patients in the three trials, no pathogen was identified in 345
      (22.1%), 423 (27.2%) had a monomicrobial infection and 790 (50.7%) had a
      polymicrobial infection. At the test-of-cure assessment, there were no
      significant differences in outcome between the two treatment groups for any of
      the three infections. Cure rates (clinical and microbiological for intra
      abdominal infection, clinical for skin/skin-structure and pelvic infections) in
      microbiologically evaluable patients for ertapenem and piperacillin-tazobactam,
      respectively, were 85.6% (154/180 evaluable patients) and 82.5% (127/154) for
      polymicrobial intra-abdominal infection, 80.3% (53/66) and 78.7% (48/61) for
      polymicrobial skin/skin-structure infection, and 95.7% (88/92) and 92.6% (88/95)
      for polymicrobial pelvic infection. Respective cure rates for all evaluable
      patients in the original trials were: 83.6% and 80.4% for intra-abdominal, 83.9%
      and 85.3% for skin/skin-structure, and 93.9% and 91.5% for pelvic infections.
      These data show that in the three trials, ertapenem 1 g once a day was highly
      effective for the treatment of polymicrobial infections and as effective as
      piperacillin-tazobactam 3.375 g every 6 h.

PMID- 15150184
TI  - Ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in
      adults: combined analysis of two multicentre randomized, double-blind studies.
AB  - The efficacy and safety of ertapenem, 1 g once a day, for the treatment of
      community-acquired pneumonia (CAP) requiring parenteral therapy were compared
      with those of ceftriaxone, 1 g once a day, in 866 hospitalized adults randomized
      in two prospective, double-blind, multicentre studies. Patients were stratified
      according to Pneumonia Severity Index (< or = 3 or >3) or age (< or = 65 or >65
      years). After > or = 3 days of parenteral antimicrobial therapy, patients who had
      clinically improved could be switched to oral co-amoxiclav. The median durations
      of parenteral, oral and total therapy in the 658 clinically evaluable patients,
      of whom 88% were switched to oral therapy, were 4, 7 and 12 days, respectively,
      in both treatment groups. The most common pathogen was Streptococcus pneumoniae,
      of which 79% (143/181) were penicillin susceptible and 3.3% (6/181; three in each
      treatment group) were penicillin resistant. Cure rates for the two treatments
      were equivalent: 91.9% for ertapenem and 92.0% for ceftriaxone (95% confidence
      interval for the difference, adjusted for strata: -4.5 to 4.4). Cure rates in the
      different severity and age strata and bacterial eradication rates for both
      treatment groups were also similar. The most common drug-related adverse events
      in both treatment groups were diarrhoea and mild-to-moderate elevations in
      aminotransferase levels. The results of these studies demonstrate that ertapenem,
      1 g once a day, was highly effective therapy for CAP in hospitalized adults with
      moderate-to-severe disease.

PMID- 15150185
TI  - Treatment of complicated urinary tract infection in adults: combined analysis of
      two randomized, double-blind, multicentre trials comparing ertapenem and
      ceftriaxone followed by appropriate oral therapy.
AB  - The efficacy and safety of parenteral ertapenem, a Group 1 carbapenem, 1 g once a
      day, for the treatment of complicated urinary tract infections (UTIs; i.e. acute
      pyelonephritis, UTI in men, or UTI associated with obstruction, foreign body or a
      urological abnormality interfering with normal voiding) in adults, were compared
      with those of parenteral ceftriaxone, 1 g once a day, in two similarly designed
      prospective, double-blind, randomized studies. In both studies, patients could be
      switched to an oral agent after > or = 3 days of parenteral study therapy. At
      entry, 850 patients were stratified according to whether they had acute
      pyelonephritis or other complicated UTI without acute pyelonephritis. Two hundred
      and fifty-six patients in the ertapenem group and 224 in the ceftriaxone group
      were microbiologically evaluable. Ninety-six per cent of these patients were
      switched to oral therapy, usually ciprofloxacin; the median (range) duration of
      parenteral and total therapy, respectively, was 4 (2-14) days and 13 (14-18) days
      for ertapenem and 4 (2-14) days and 13 (3-17) days for ceftriaxone. The most
      common pathogens were Escherichia coli and Klebsiella pneumoniae, which accounted
      for 64.7% and 9.8% of isolates, respectively. At the primary efficacy endpoint 5
      9 days after treatment, 229 (89.5%) patients who received ertapenem and 204
      (91.1%) patients who received ceftriaxone had a favourable microbiological
      response (95% confidence interval, -7.4 to 4.0), indicating that outcomes in the
      two treatment groups were equivalent. Success rates in both treatment groups were
      similar when compared by stratum and severity of infection. The frequency and
      severity of drug-related adverse events were generally similar in both treatment
      groups. In this combined analysis, ertapenem was highly effective therapy for the
      treatment of complicated UTIs in adults with moderate-to-severe disease.

PMID- 15150186
TI  - Safety and tolerability of ertapenem.
AB  - Ertapenem is a Group 1 carbapenem that was licensed in the USA in November 2001
      and in Europe in April 2002. Its safety profile has been assessed in 240 healthy
      volunteers participating in 12 clinical pharmacology studies and in 2046 patients
      enrolled in five Phase IIa and eight Phase IIb/III clinical trials. The most
      common drug-related adverse events (AEs) reported in trials comparing ertapenem
      and piperacillin-tazobactam and in trials comparing ertapenem and ceftriaxone
      were: diarrhoea (ertapenem versus piperacillin-tazobactam 5.0% versus 7.0%;
      ertapenem versus ceftriaxone 5.6% versus 5.9%); infused vein complications
      (ertapenem versus piperacillin-tazobactam 4.5% versus 7.9%; ertapenem versus
      ceftriaxone 3.2% versus 4.6%); nausea (ertapenem versus piperacillin-tazobactam
      2.5% versus 3.4%; ertapenem versus ceftriaxone 3.4% versus 3.3%); and elevations
      in alanine aminotransferase levels (ertapenem versus piperacillin-tazobactam 8.8%
      versus 7.3%; ertapenem versus ceftriaxone 8.3% versus 6.9%). Most ertapenem
      related AEs were reported as mild-to-moderate in intensity. Ertapenem was not
      associated with prolongation of the QTc interval. Local reactions of moderate-to
      severe intensity at the infusion site were infrequent and occurred with similar
      frequency in the ertapenem and comparator treatment groups. No overall
      differences in safety were observed between elderly (aged > or = 65 years and >
      or = 75 years) and younger patients. Ertapenem, 1 g once a day given by
      intravenous infusion or intramuscular injection, was generally well tolerated and
      had overall safety and tolerability profiles similar to those of piperacillin
      tazobactam and ceftriaxone.

PMID- 15150188
TI  - Scientists probe shutting down cancer cells by awakening silenced genes.

PMID- 15150187
TI  - Ertapenem: a new opportunity for outpatient parenteral antimicrobial therapy.
AB  - Ertapenem is a parenteral carbapenem antimicrobial with pharmacological
      properties that allow it to be given once daily. This makes it a consideration
      for outpatient parenteral antimicrobial therapy (OPAT). In comparison with
      information from the OPAT Outcomes Registry, ertapenem seems well suited for the
      types of infections and bacteria that are commonly treated with OPAT, plus it has
      additional activity against anaerobic bacteria. This added spectrum makes it
      possible to treat complicated skin/skin-structure, complicated intra-abdominal
      and pelvic infections with a single antibiotic instead of the multiple agents
      that have usually been required. Ertapenem is also comparable to other OPAT
      antimicrobials in terms of adverse effects and clinical outcomes. This
      antimicrobial can be given with any delivery model, although its stability when
      mixed is such that daily preparation or self-mixing systems need to be
      considered. Ertapenem should be added to the growing list of once-daily
      parenteral antibiotics that can be given to outpatients.

PMID- 15150189
TI  - Forecast for US uninsured remains gloomy.

PMID- 15150190
TI  - Group calls for stricter rules for assisted reproduction, ban of "extreme"
      technologies.

PMID- 15150198
TI  - Usefulness of the Glasgow Coma Score in survivors of cardiac arrest.

PMID- 15150199
TI  - Risk of contact vaccinia from immunization sites.

PMID- 15150200
TI  - Risk of contact vaccinia from immunization sites.

PMID- 15150201
TI  - Guidelines for home- and office-based blood pressure monitoring.

PMID- 15150202
TI  - The debt repayment paradox for VA clinical investigators.

PMID- 15150203
TI  - Terminal complement blockade with pexelizumab during coronary artery bypass graft
      surgery requiring cardiopulmonary bypass: a randomized trial.
AB  - CONTEXT: Inflammation and ischemia-reperfusion injury during coronary artery
      bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with
      postoperative myocardial infarction (MI) and mortality. OBJECTIVE: To determine
      the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing
      perioperative MI and mortality in CABG surgery. DESIGN, SETTING, AND
      PARTICIPANTS: A randomized, double-blind, placebo-controlled trial, including
      3099 patients (> or = 18 years) undergoing CABG surgery with or without valve
      surgery at 205 hospitals in North America and Western Europe from January 2002 to
      February 2003. INTERVENTIONS: Patients were randomly assigned to receive
      intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n
      = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. MAIN
      OUTCOME MEASURES: The primary composite end point was the incidence of death or
      MI within 30 days of randomization in those undergoing CABG surgery only (n =
      2746). Secondary analyses included the intent-to-treat analyses of death or MI
      composite at days 4 and 30 in all 3099 study patients. RESULTS: After 30 days,
      134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of
      patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66
      1.02; P =.07) died or experienced MI in the CABG surgery only population. In the
      intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs
      215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk,
      0.82; 95% confidence interval, 0.68-0.99; P =.03). The trial was not powered to
      detect a reduction in mortality alone. CONCLUSIONS: Compared with placebo,
      pexelizumab was not associated with a significant reduction in the risk of the
      composite end point of death or MI in 2746 patients who had undergone CABG
      surgery only but was associated with a statistically significant risk reduction
      30 days after the procedure among all 3099 patients undergoing CABG with or
      without valve surgery.

PMID- 15150204
TI  - Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized
      controlled trial.
AB  - CONTEXT: Contrast-induced nephropathy remains a common complication of
      radiographic procedures. Pretreatment with sodium bicarbonate is more protective
      than sodium chloride in animal models of acute ischemic renal failure. Acute
      renal failure from both ischemia and contrast are postulated to occur from free
      radical injury. However, no studies in humans or animals have evaluated the
      efficacy of sodium bicarbonate for prophylaxis against contrast-induced
      nephropathy. OBJECTIVE: To examine the efficacy of sodium bicarbonate compared
      with sodium chloride for preventive hydration before and after radiographic
      contrast. DESIGN, SETTING, AND PATIENTS: A prospective, single-center, randomized
      trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with
      stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who
      were randomized to receive a 154-mEq/L infusion of either sodium chloride (n =
      59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370
      mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days
      after contrast. INTERVENTIONS: Patients received 154 mEq/L of either sodium
      chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before
      iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after
      the procedure. MAIN OUTCOME MEASURE: Contrast-induced nephropathy, defined as an
      increase of 25% or more in serum creatinine within 2 days of contrast. RESULTS:
      There were no significant group differences in age, sex, incidence of diabetes
      mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly
      higher but not statistically different in patients receiving sodium bicarbonate
      treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium
      chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate;
      P =.09). The primary end point of contrast-induced nephropathy occurred in 8
      patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those
      receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval
      [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients
      receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria
      as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI,
      0%-3.4%). CONCLUSION: Hydration with sodium bicarbonate before contrast exposure
      is more effective than hydration with sodium chloride for prophylaxis of contrast
      induced renal failure.

PMID- 15150205
TI  - Recovery and long-term function after hematopoietic cell transplantation for
      leukemia or lymphoma.
AB  - CONTEXT: Hematopoietic cell transplantation (HCT) is an effective and widely used
      treatment for hematologic malignancies. The rate and predictors of physical and
      emotional recovery after HCT have not been adequately defined in prospective long
      term studies. OBJECTIVE: To examine the course of recovery and return to work
      after HCT. DESIGN, SETTING, AND PATIENTS: Prospective, longitudinal cohort study
      at a US academic center specializing in HCT. Function was assessed from
      pretransplantation to 5-year follow-up for 319 adults who had myeloablative HCT
      for treatment of leukemia or lymphoma and spoke English. Of the 99 long-term
      survivors who had no recurrent malignancy, 94 completed 5-year follow-up. MAIN
      OUTCOME MEASURES: Physical limitations, return to work, depression, and distress
      related to treatment or disease were evaluated before transplantation, at 90
      days, and at 1, 3, and 5 years after HCT. RESULTS: Physical recovery occurred
      earlier than psychological or work recovery. Only 21 patients (19%) recovered on
      all outcomes at 1 year. The proportion without major limitations increased to 63%
      (n = 57) by 5 years. Among survivors without recurrent malignancy, 84% (n = 74)
      returned to full-time work by 5 years. Patients with slower physical recovery had
      higher medical risk and were more depressed before HCT (P< or =.001). Patients
      with chronic graft-vs-host disease (P =.01), with less social support before HCT
      (P =.001), and women (P<.001) were more depressed after transplantation.
      Transplant-related distress was slower to recover for allogeneic transplant
      recipients and those with less social support before HCT (P< or =.01). Patients
      who had more experience with cancer treatment before beginning HCT had more rapid
      recovery from depression (P =.04) and treatment-related distress (P =.009).
      CONCLUSIONS: Full recovery after HCT is a 3- to 5-year process. Recovery might be
      accelerated by more effective interventions to increase work-related
      capabilities, improve social support, and manage depression.

PMID- 15150206
TI  - Pharmacy benefits and the use of drugs by the chronically ill.
AB  - CONTEXT: Many health plans have instituted more cost sharing to discourage use of
      more expensive pharmaceuticals and to reduce drug spending. OBJECTIVE: To
      determine how changes in cost sharing affect use of the most commonly used drug
      classes among the privately insured and the chronically ill. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective US study conducted from 1997 to 2000, examining
      linked pharmacy claims data with health plan benefit designs from 30 employers
      and 52 health plans. Participants were 528,969 privately insured beneficiaries
      aged 18 to 64 years and enrolled from 1 to 4 years (960,791 person-years). MAIN
      OUTCOME MEASURE: Relative change in drug days supplied (per member, per year)
      when co-payments doubled in a prototypical drug benefit plan. RESULTS: Doubling
      co-payments was associated with reductions in use of 8 therapeutic classes. The
      largest decreases occurred for nonsteroidal anti-inflammatory drugs (NSAIDs)
      (45%) and antihistamines (44%). Reductions in overall days supplied of
      antihyperlipidemics (34%), antiulcerants (33%), antiasthmatics (32%),
      antihypertensives (26%), antidepressants (26%), and antidiabetics (25%) were also
      observed. Among patients diagnosed as having a chronic illness and receiving
      ongoing care, use was less responsive to co-payment changes. Use of
      antidepressants by depressed patients declined by 8%; use of antihypertensives by
      hypertensive patients decreased by 10%. Larger reductions were observed for
      arthritis patients taking NSAIDs (27%) and allergy patients taking antihistamines
      (31%). Patients with diabetes reduced their use of antidiabetes drugs by 23%.
      CONCLUSIONS: The use of medications such as antihistamines and NSAIDs, which are
      taken intermittently to treat symptoms, was sensitive to co-payment changes.
      Other medications--antihypertensive, antiasthmatic, antidepressant,
      antihyperlipidemic, antiulcerant, and antidiabetic agents--also demonstrated
      significant price responsiveness. The reduction in use of medications for
      individuals in ongoing care was more modest. Still, significant increases in co
      payments raise concern about adverse health consequences because of the large
      price effects, especially among diabetic patients.

PMID- 15150207
TI  - Impact of thimerosal-related changes in hepatitis B vaccine birth-dose
      recommendations on childhood vaccination coverage.
AB  - CONTEXT: In July 1999, the longstanding preference to begin hepatitis B
      vaccination of all US infants at birth was temporarily suspended because of
      concerns about exposure to mercury contained in the vaccine preservative
      thimerosal. The suspension was lifted in September 1999 when preservative-free
      hepatitis B vaccine became available. OBJECTIVE: To determine the effects of
      changes in recommendations regarding administration of a hepatitis B birth dose
      on vaccination coverage. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of
      vaccination status of 41,589 US children born before, during, and after the
      recommendation to suspend the birth dose. MAIN OUTCOME MEASURES: Association
      between birth cohort and age at receipt of hepatitis B vaccine dose 1, and
      receipt by 19 months of age of all recommended vaccines. RESULTS: The proportion
      of US infants who received dose 1 of hepatitis B vaccine at birth declined from
      47% among those born 7 to 12 months before the suspension to 11% among those born
      during the suspension. Birth-dose coverage remained significantly lower in the
      year after the suspension was lifted (23% in the first 6 months and 33% in months
      7-12). Coverage with 3 doses of hepatitis B vaccine by 19 months of age declined
      from 88% among those born 7 to 12 months before the suspension to 81% among those
      born during the suspension and 85% among those born in the 6 months after the
      suspension, but returned to baseline levels for those born 7 to 12 months after
      the suspension was lifted. These reductions represent 750,000 fewer newborns
      vaccinated during 2000 compared with 1998, and an excess 182,000 children
      undervaccinated for hepatitis B at 19 months of age compared with 1998 coverage
      levels. Coverage with other recommended vaccinations did not decline over this
      time. CONCLUSIONS: Reductions in hepatitis B vaccine birth-dose coverage
      persisted after recommendations were made to resume previous newborn vaccination
      practices. Although the recommendation to complete the series by 19 months of age
      was never changed, infants born between July and December 1999 were less likely
      to have completed the series by 19 months, compared with infants born during the
      previous year. The lack of impact on other vaccinations suggests that public
      confidence in immunization remained strong.

PMID- 15150209
TI  - Intravenous immunoglobulin in autoimmune neuromuscular diseases.
AB  - CONTEXT: Intravenous immunoglobulin (IVIG) enhances immune homeostasis by
      modulating expression and function of Fc receptors, interfering with activation
      of complement and production of cytokines, providing anti-idiotypic antibodies,
      and affecting the activation and effector functions of T and B cells. These
      mechanisms may explain the effectiveness of IVIG in autoimmune neuromuscular
      disorders. OBJECTIVE: To systematically review the current status of the
      treatment of autoimmune neuromuscular diseases with IVIG, with emphasis on
      controlled trials. DATA SOURCES: Peer-reviewed publications identified through
      MEDLINE (1966-2003), EMBASE (1974-2003), and references from bibliographies of
      pertinent articles. Each autoimmune neuromuscular disease term was searched in
      combination with the term intravenous immunoglobulin. STUDY SELECTION AND DATA
      EXTRACTION: Criteria for selection of studies included controlled study design,
      English language, and clinical pertinence. Data quality was based on venue of
      publication and relevance to clinical care. DATA SYNTHESIS: Outcomes of
      controlled trials indicate that IVIG at a total dose of 2 g/kg is effective as
      first-line therapy in Guillain-Barre syndrome, chronic inflammatory demyelinating
      polyneuropathy, and multifocal motor neuropathy and as second-line therapy in
      stiff-person syndrome, dermatomyositis, myasthenia gravis, and Lambert-Eaton
      myasthenic syndrome. In other controlled studies, IVIG produced a modest,
      variable, and transient but not statistically significant benefit in patients
      with inclusion body myositis and paraproteinemic anti-myelin-associated
      glycoprotein antibody demyelinating polyneuropathy. Intravenous immunoglobulin is
      not effective in patients with multiple sclerosis who have established weakness
      or optic neuritis. In myasthenia gravis, it should be reserved for difficult
      cases or before thymectomy in lieu of plasma exchange. CONCLUSION: Intravenous
      immunoglobulin is effective in many autoimmune neurologic diseases, but its
      spectrum of efficacy, especially as first-line therapy, and the appropriate dose
      for long-term maintenance therapy are not fully established. Further controlled
      studies of IVIG, combined with a dose-finding effect, pharmacoeconomics, and
      quality-of-life assessments, are warranted to improve the evidence base for
      clinical practice.

PMID- 15150210
TI  - Prevention of radiocontrast nephropathy: back to basics.

PMID- 15150208
TI  - Communicating evidence for participatory decision making.
AB  - CONTEXT: Informed patients are more likely to actively participate in their care,
      make wiser decisions, come to a common understanding with their physicians, and
      adhere more fully to treatment; however, currently there are no evidence-based
      guidelines for discussing clinical evidence with patients in the process of
      making medical decisions. OBJECTIVE: To identify ways to communicate evidence
      that improve patient understanding, involvement in decisions, and outcomes. DATA
      SOURCES AND STUDY SELECTION: Systematic review of MEDLINE for the period 1966
      2003 and review of reference lists of retrieved articles to identify original
      research dealing with communication between clinicians and patients and directly
      addressing methods of presenting clinical evidence to patients. DATA EXTRACTION:
      Two investigators and a research assistant screened 367 abstracts and 2
      investigators reviewed 51 full-text articles, yielding 8 potentially relevant
      articles. DATA SYNTHESIS: Methods for communicating clinical evidence to patients
      include nonquantitative general terms, numerical translation of clinical
      evidence, graphical representations, and decision aids. Focus-group data suggest
      presenting options and/or equipoise before asking patients about preferred
      decision-making roles or formats for presenting details. Relative risk reductions
      may be misleading; absolute risk is preferred. Order of information presented and
      time-frame of outcomes can bias patient understanding. Limited evidence supports
      use of human stick figure graphics or faces for single probabilities and vertical
      bar graphs for comparative information. Less-educated and older patients
      preferred proportions to percentages and did not appreciate confidence intervals.
      Studies of decision aids rarely addressed patient-physician communication
      directly. No studies addressed clinical outcomes of discussions of clinical
      evidence. CONCLUSIONS: There is a paucity of evidence to guide how physicians can
      most effectively share clinical evidence with patients facing decisions; however,
      basing our recommendations largely on related studies and expert opinion, we
      describe means of accomplishing 5 communication tasks to address in framing and
      communicating clinical evidence: understanding the patient's (and family
      members') experience and expectations; building partnership; providing evidence,
      including a balanced discussion of uncertainties; presenting recommendations
      informed by clinical judgment and patient preferences; and checking for
      understanding and agreement.

PMID- 15150211
TI  - JAMA patient page. Cochlear implants.

PMID- 15150212
TI  - Refining our perception of bacterial surfaces with the atomic force microscope.

PMID- 15150213
TI  - Atomic force microscopy of cell growth and division in Staphylococcus aureus.
AB  - The growth and division of Staphylococcus aureus was monitored by atomic force
      microscopy (AFM) and thin-section transmission electron microscopy (TEM). A good
      correlation of the structural events of division was found using the two
      microscopies, and AFM was able to provide new additional information. AFM was
      performed under water, ensuring that all structures were in the hydrated
      condition. Sequential images on the same structure revealed progressive changes
      to surfaces, suggesting the cells were growing while images were being taken.
      Using AFM small depressions were seen around the septal annulus at the onset of
      division that could be attributed to so-called murosomes (Giesbrecht et al.,
      Arch. Microbiol. 141:315-324, 1985). The new cell wall formed from the cross wall
      (i.e., completed septum) after cell separation and possessed concentric surface
      rings and a central depression; these structures could be correlated to a midline
      of reactive material in the developing septum that was seen by TEM. The older
      wall, that which was not derived from a newly formed cross wall, was partitioned
      into two different surface zones, smooth and gel-like zones, with different
      adhesive properties that could be attributed to cell wall turnover. The new and
      old wall topographies are equated to possible peptidoglycan arrangements, but no
      conclusion can be made regarding the planar or scaffolding models.

PMID- 15150214
TI  - Secretion of virulence proteins from Campylobacter jejuni is dependent on a
      functional flagellar export apparatus.
AB  - Campylobacter jejuni, a gram-negative motile bacterium, secretes a set of
      proteins termed the Campylobacter invasion antigens (Cia proteins). The purpose
      of this study was to determine whether the flagellar apparatus serves as the
      export apparatus for the Cia proteins. Mutations were generated in five genes
      encoding three structural components of the flagella, the flagellar basal body
      (flgB and flgC), hook (flgE2), and filament (flaA and flaB) genes, as well as in
      genes whose products are essential for flagellar protein export (flhB and fliI).
      While mutations that affected filament assembly were found to be nonmotile (Mot-)
      and did not secrete Cia proteins (S-), a flaA (flaB+) filament mutant was found
      to be nonmotile but Cia protein secretion competent (Mot-, S+). Complementation
      of a flaA flaB double mutant with a shuttle plasmid harboring either the flaA or
      flaB gene restored Cia protein secretion, suggesting that Cia export requires at
      least one of the two filament proteins. Infection of INT 407 human intestinal
      cells with the C. jejuni mutants revealed that maximal invasion of the epithelial
      cells required motile bacteria that are secretion competent. Collectively, these
      data suggest that the C. jejuni Cia proteins are secreted from the flagellar
      export apparatus.

PMID- 15150215
TI  - Isolation and characterization of rpoS from a pathogenic bacterium, Vibrio
      vulnificus: role of sigmaS in survival of exponential-phase cells under oxidative
      stress.
AB  - A gene homologous to rpoS was cloned from a fatal human pathogen, Vibrio
      vulnificus. The functional role of rpoS in V. vulnificus was accessed by using an
      rpoS knockout mutant strain. This mutant was impaired in terms of the ability to
      survive under oxidative stress, nutrient starvation, UV irradiation, or acidic
      conditions. The increased susceptibility of the V. vulnificus mutant in the
      exponential phase to H2O2 was attributed to the reduced activity of
      hydroperoxidase I (HPI). Although sigmaS synthesis was induced and HPI activity
      reached the maximal level in the stationary phase, the mutant in the stationary
      phase showed the same susceptibility to H2O2 as the wild-type strain in the
      stationary phase. In addition, HPII activity, which is known to be controlled by
      sigmaS in Escherichia coli, was not detectable in V. vulnificus strains under the
      conditions tested. The mutant in the exponential phase complemented with multiple
      copies of either the rpoS or katG gene of V. vulnificus recovered both resistance
      to H2O2 and HPI activity compared with the control strain. Expression of the katG
      gene encoding HPI in V. vulnificus was monitored by using a katG::luxAB
      transcriptional fusion. The expression of this gene was significantly reduced by
      deletion of sigmaS in both the early exponential and late stationary phases.
      Thus, sigmaS is necessary for increased synthesis and activity of HPI, and sigmaS
      is required for exponentially growing V. vulnificus to develop the ability to
      survive in the presence of H2O2.

PMID- 15150216
TI  - Circularized chromosome with a large palindromic structure in Streptomyces
      griseus mutants.
AB  - Streptomyces linear chromosomes display various types of rearrangements after
      telomere deletion, including circularization, arm replacement, and amplification.
      We analyzed the new chromosomal deletion mutants Streptomyces griseus 301-22-L
      and 301-22-M. In these mutants, chromosomal arm replacement resulted in long
      terminal inverted repeats (TIRs) at both ends; different sizes were deleted again
      and recombined inside the TIRs, resulting in a circular chromosome with an
      extremely large palindrome. Short palindromic sequences were found in parent
      strain 2247, and these sequences might have played a role in the formation of
      this unique structure. Dynamic structural changes of Streptomyces linear
      chromosomes shown by this and previous studies revealed extraordinary strategies
      of members of this genus to keep a functional chromosome, even if it is linear or
      circular.

PMID- 15150217
TI  - The spatial organization of the VirR boxes is critical for VirR-mediated
      expression of the perfringolysin O gene, pfoA, from Clostridium perfringens.
AB  - The transcriptional regulation of toxin production in the gram-positive anaerobe
      Clostridium perfringens involves a two-component signal transduction system that
      comprises the VirS sensor histidine kinase and its cognate response regulator,
      VirR. Previous studies showed that VirR binds independently to a pair of
      imperfect direct repeats, now designated VirR box 1 and VirR box 2, located
      immediately upstream of the promoter of the pfoA gene, which encodes the
      cholesterol-dependent cytolysin, perfringolysin O. For this study, we introduced
      mutated VirR boxes into a C. perfringens pfoA mutant and found that both VirR
      boxes are essential for transcriptional activation. Furthermore, the spacing
      between the VirR boxes and the distance between the VirR boxes and the -35 region
      are shown to be critical for perfringolysin O production. Other VirR boxes that
      were previously identified from the strain 13 genome sequence were also analyzed,
      with perfringolysin O production used as a reporter system. The results showed
      that placement of the different VirR boxes at the same position upstream of the
      pfoA promoter yields different levels of perfringolysin O activity. In all of
      these constructs, VirR was still capable of binding to the target DNA, indicating
      that DNA binding alone is not sufficient for transcriptional activation. Finally,
      we show that the C. perfringens RNA polymerase binds more efficiently to the pfoA
      promoter in the presence of VirR, indicating that interactions must occur between
      these proteins. We propose that these interactions are required for VirR-mediated
      transcriptional activation.

PMID- 15150218
TI  - Differential gene expression in response to hydrogen peroxide and the putative
      PerR regulon of Synechocystis sp. strain PCC 6803.
AB  - We utilized a full genome cDNA microarray to identify the genes that comprise the
      peroxide stimulon in the cyanobacterium Synechocystis sp. strain PCC 6803. We
      determined that a gene (slr1738) encoding a protein similar to PerR in Bacillus
      subtilis was induced by peroxide. We constructed a PerR knockout strain and used
      it to help identify components of the PerR regulon, and we found that the
      regulatory properties were consistent with the hypothesis that PerR functions as
      a repressor. This effort was guided by finding putative PerR boxes in positions
      upstream of specific genes and by careful statistical analysis. PerR and sll1621
      (ahpC), which codes for a peroxiredoxin, share a divergent promoter that is
      regulated by PerR. We found that isiA, encoding a Chl protein that is induced
      under low-iron conditions, was strongly induced by a short-term peroxide stress.
      Other genes that were strongly induced by peroxide included sigD, sigB, and genes
      encoding peroxiredoxins and Dsb-like proteins that have not been studied yet in
      this strain. A gene (slr1894) that encoded a protein similar to MrgA in B.
      subtilis was upregulated by peroxide, and a strain containing an mrgA knockout
      mutation was highly sensitive to peroxide. A number of genes were downregulated,
      including key genes in the chlorophyll biosynthesis pathway and numerous
      regulatory genes, including those encoding histidine kinases. We used PerR
      mutants and a thioredoxin mutant (TrxA1) to study differential expression in
      response to peroxide and determined that neither PerR nor TrxA1 is essential for
      the peroxide protective response.

PMID- 15150219
TI  - Interactions between the nitrogen signal transduction protein PII and N-acetyl
      glutamate kinase in organisms that perform oxygenic photosynthesis.
AB  - PII, one of the most conserved signal transduction proteins, is believed to be a
      key player in the coordination of nitrogen assimilation and carbon metabolism in
      bacteria, archaea, and plants. However, the identity of PII receptors remains
      elusive, particularly in photosynthetic organisms. Here we used yeast two-hybrid
      approaches to identify new PII receptors and to explore the extent of
      conservation of PII signaling mechanisms between eubacteria and photosynthetic
      eukaryotes. Screening of Synechococcus sp. strain PCC 7942 libraries with PII as
      bait resulted in identification of N-acetyl glutamate kinase (NAGK), a key enzyme
      in the biosynthesis of arginine. The integrity of Ser49, a residue conserved in
      PII proteins from organisms that perform oxygenic photosynthesis, appears to be
      essential for NAGK binding. The effect of glnB mutations on NAGK activity is
      consistent with positive regulation of NAGK by PII. Phylogenetic and yeast two
      hybrid analyses strongly suggest that there was conservation of the NAGK-PII
      regulatory interaction in the evolution of cyanobacteria and chloroplasts,
      providing insight into the function of eukaryotic PII-like proteins.

PMID- 15150220
TI  - The RNA-binding protein Hfq of Listeria monocytogenes: role in stress tolerance
      and virulence.
AB  - In gram-negative bacteria, the RNA-binding protein Hfq has emerged as an
      important regulatory factor in a variety of physiological processes, including
      stress resistance and virulence. In Escherichia coli, Hfq modulates the stability
      or the translation of mRNAs and interacts with numerous small regulatory RNAs.
      Here, we studied the role of Hfq in the stress tolerance and virulence of the
      gram-positive food-borne human pathogen Listeria monocytogenes. We present
      evidence that Hfq is involved in the ability of L. monocytogenes to tolerate
      osmotic and ethanol stress and contributes to long-term survival under amino acid
      limiting conditions. However, Hfq is not required for resistance to acid and
      oxidative stress. Transcription of hfq is induced under various stress
      conditions, including osmotic and ethanol stress and at the entry into the
      stationary growth phase, thus supporting the view that Hfq is important for the
      growth and survival of L. monocytogenes in harsh environments. The stress
      inducible transcription of hfq depends on the alternative sigma factor sigmaB,
      which controls the expression of numerous stress- and virulence-associated genes
      in L. monocytogenes. Infection studies showed that Hfq contributes to
      pathogenesis in mice, yet plays no role in the infection of cultured cell lines.
      This study provides, for the first time, information on the role of Hfq in the
      stress tolerance and virulence of a gram-positive pathogen.

PMID- 15150221
TI  - An accessory protein is required for relaxosome formation by small staphylococcal
      plasmids.
AB  - Mobilization of the staphylococcal plasmid pC221 requires at least one plasmid
      encoded protein, MobA, in order to form a relaxosome. pC221 and closely related
      plasmids also possess an overlapping reading frame encoding a protein of 15 kDa,
      termed MobC. By completing the nucleotide sequence of plasmid pC223, we have
      found a further example of this small protein, and gene knockouts have shown that
      MobC is essential for relaxosome formation and plasmid mobilization in both pC221
      and pC223. Primer extension analysis has been used to identify the nic site in
      both of these plasmids, located upstream of the mobC gene in the sense strand.
      Although the sequence surrounding the nic site is highly conserved between pC221
      and pC223, exchange of the oriT sequence between plasmids significantly reduces
      the extent of relaxation complex formation, suggesting that the Mob proteins are
      selective for their cognate plasmids in vivo.

PMID- 15150222
TI  - Reconstitution of a staphylococcal plasmid-protein relaxation complex in vitro.
AB  - The isolation of plasmid-protein relaxation complexes from bacteria is indicative
      of the plasmid nicking-closing equilibrium in vivo that serves to ready the
      plasmids for conjugal transfer. In pC221 and pC223, the components required for
      in vivo site- and strand-specific nicking at oriT are MobC and MobA. In order to
      investigate the minimal requirements for nicking in the absence of host-encoded
      factors, the reactions were reconstituted in vitro. Purified MobA and MobC, in
      the presence of Mg2+ or Mn2+, were found to nick at oriT with a concomitant
      phosphorylation-resistant modification at the 5' end of nic. The position of nic
      is consistent with that determined in vivo. MobA, MobC, and Mg2+ or Mn2+
      therefore represent the minimal requirements for nicking activity. Cross
      complementation analyses showed that the MobC proteins possess binding
      specificity for oriT DNA of either plasmid and are able to complement each other
      in the nicking reaction. Conversely, nicking by the MobA proteins is plasmid
      specific. This suggests the MobA proteins may encode the nicking specificity
      determinant.

PMID- 15150223
TI  - Stress response gene regulation in Chlamydia is dependent on HrcA-CIRCE
      interactions.
AB  - HrcA is a transcriptional repressor that regulates stress response genes in many
      bacteria by binding to the CIRCE operator. We have previously shown that HrcA
      regulates the promoter for the dnaK heat shock operon in Chlamydia. Here we
      demonstrate that HrcA represses a second heat shock promoter that controls the
      expression of groES and groEL, two other major chlamydial heat shock genes. The
      CIRCE element of C. trachomatis groEL is the most divergent of known bacterial
      CIRCE elements, and HrcA had a decreased ability to bind to this nonconsensus
      operator and repress transcription. We demonstrate that the CIRCE element is
      necessary and sufficient for transcriptional regulation by chlamydial HrcA and
      that the inverted repeats of CIRCE are the binding sites for HrcA. Addition of a
      CIRCE element upstream of a non-heat-shock promoter allowed this promoter to be
      repressed by HrcA, showing in principle that a chlamydial promoter can be
      genetically modified to be inducible. These results demonstrate that HrcA is the
      regulator of the major chlamydial heat shock operons, and we infer that the
      mechanism of the heat shock response in Chlamydia is derepression. However,
      derepression is likely to involve more than a direct effect of increased
      temperature as we found that HrcA binding to CIRCE and HrcA-mediated repression
      were not altered at temperatures that induce the heat shock response.

PMID- 15150224
TI  - CcpA-dependent regulation of Bacillus subtilis glutamate dehydrogenase gene
      expression.
AB  - The Bacillus subtilis rocG gene, encoding catabolic glutamate dehydrogenase, was
      found to be subject to direct CcpA-dependent glucose repression. The effect of
      CcpA required the presence of both the HPr and Crh proteins. The primary CcpA
      binding site was identified by mutational analysis and DNase I footprinting. In
      the absence of inducers of the Roc pathway, rocG was still expressed at a low
      level due to readthrough transcription. CcpA-dependent repression of rocG
      readthrough transcription proved to contribute to the slow growth rate of B.
      subtilis cells in glucose-glutamate medium. Increased readthrough expression of
      rocG was shown to be partially responsible for the growth defect of ccpA strains
      in glucose-ammonium medium.

PMID- 15150225
TI  - Modulation of activity of Bacillus subtilis regulatory proteins GltC and TnrA by
      glutamate dehydrogenase.
AB  - The Bacillus subtilis gltAB operon, encoding glutamate synthase, requires a
      specific positive regulator, GltC, for its expression and is repressed by the
      global regulatory protein TnrA. The factor that controls TnrA activity, a complex
      of glutamine synthetase and a feedback inhibitor, such as glutamine, is known,
      but the signal for modulation of GltC activity has remained elusive. GltC
      dependent gltAB expression was drastically reduced when cells were grown in media
      containing arginine or ornithine or proline, all of which are inducers and
      substrates of the Roc catabolic pathway. Analysis of gltAB expression in mutants
      with various defects in the Roc pathway indicated that rocG-encoded glutamate
      dehydrogenase was required for such repression, suggesting that the substrates or
      products of this enzyme are the real effectors of GltC. Given that RocG is an
      enzyme of glutamate catabolism, the main regulatory role of GltC may be
      prevention of a futile cycle of glutamate synthesis and degradation in the
      presence of arginine-related amino acids or proline. In addition, high activity
      of glutamate dehydrogenase was incompatible with activity of TnrA.

PMID- 15150226
TI  - A cambialistic superoxide dismutase in the thermophilic photosynthetic bacterium
      Chloroflexus aurantiacus.
AB  - Superoxide dismutase from the thermophilic anoxygenic photosynthetic bacterium
      Chloroflexus aurantiacus was cloned, purified, and characterized. This protein is
      in the manganese- and iron-containing family of superoxide dismutases and is able
      to use both manganese and iron catalytically. This appears to be the only soluble
      superoxide dismutase in C. aurantiacus. Iron and manganese cofactors were
      identified by using electron paramagnetic resonance spectroscopy and were
      quantified by atomic absorption spectroscopy. By metal enrichment of growth media
      and by performing metal fidelity studies, the enzyme was found to be most
      efficient with manganese incorporated, yet up to 30% of the activity was retained
      with iron. Assimilation of iron or manganese ions into superoxide dismutase was
      also found to be affected by the growth conditions. This enzyme was also found to
      be remarkably thermostable and was resistant to H2O2 at concentrations up to 80
      mM. Reactive oxygen defense mechanisms have not been previously characterized in
      the organisms belonging to the phylum Chloroflexi. These systems are of interest
      in C. aurantiacus since this bacterium lives in a hyperoxic environment and is
      subject to high UV radiation fluxes.

PMID- 15150227
TI  - Mechanism of intrinsic resistance to vancomycin in Clostridium innocuum NCIB
      10674.
AB  - We have studied the basis for intrinsic resistance to low levels of vancomycin in
      Clostridium innocuum NCIB 10674 (MIC = 8 microg/ml). Analysis by high-pressure
      liquid chromatography (HPLC) and mass spectrometry of peptidoglycan nucleotide
      precursors pools revealed the presence of two types of UDP-MurNac-pentapeptide
      precursors constitutively produced, an UDP-MurNAc-pentapeptide with a serine at
      the C terminus which represented 93% of the pool and an UDP-MurNAc-pentapeptide
      with an alanine at the C terminus which represented the rest of the pool. C.
      innocuum cell wall muropeptides containing pentapeptide[Ser], either dialanine
      substituted on the epsilon amino group of lysine or not, were identified and
      represented about 10% of the monomers while only 1% of pentapeptide[D-Ala]
      monomers were found. The sequence of a 2,465-bp chromosomal fragment from C.
      innocuum was determined and revealed the presence of ddl(c. innocuum) and C.
      innocuum racemase genes putatively encoding homologues of D-Ala:D-X ligases and
      amino acid racemases, respectively. Analysis of the pool of precursors of
      Enterococcus faecalis JH2-2, containing cloned ddl(c. innocuum) and C. innocuum
      racemase genes showed in addition to the UDP-MurNAc-pentapeptide[D-Ala], the
      presence of an UDP-MurNAc-pentapeptide[D-Ser] precursor. However, the expression
      of low-level resistance to vancomycin was observed only when both genes were
      cloned in E. faecalis JH2-2 together with the vanXYc gene from Enterococcus
      gallinarum BM4174 which encodes a d,d-peptidase which eliminates preferentially
      the high affinity vancomycin UDP-MurNAc-pentapeptide [D-Ala] precursors produced
      by the host. We conclude that resistance to vancomycin in C. innocuum NCIB 10674
      was related to the presence of the two chromosomal ddl(c. innocuum) and C.
      innocuum racemase genes allowing the synthesis of a peptidoglycan precursor
      terminating in serine with low affinity for vancomycin.

PMID- 15150228
TI  - Cloning and functional analysis by gene disruption of a gene encoding a gamma
      butyrolactone autoregulator receptor from Kitasatospora setae.
AB  - Gamma-butyrolactone autoregulator receptors of the genus Streptomyces have a
      common activity as DNA-binding transcriptional repressors, controlling secondary
      metabolism and/or morphological differentiation. A gene encoding a gamma
      butyrolactone autoregulator receptor was cloned from a bafilomycin B1 producer,
      Kitasatospora setae, for the first time from a non-Streptomyces genus of
      actinomycetes, and its function was evaluated by in vitro and in vivo analyses.
      The gene fragment was initially cloned by PCR with primers designed from two
      highly conserved regions of Streptomyces autoregulator receptors (BarA, FarA,
      ScbR, and ArpA), followed by genomic Southern hybridization yielding a 7-kb BamHI
      fragment on which a 654-bp receptor gene (ksbA) was identified. The recombinant
      KsbA protein demonstrated clear binding activity toward 3H-labeled
      autoregulators, especially toward [3H]SCB1, confirming that ksbA encodes a real
      autoregulator receptor of K. setae. To clarify the in vivo function of ksbA, a
      ksbA-disrupted strain was constructed by means of homologous recombination after
      introducing a ksbA disruption construct via transconjugation from Escherichia
      coli. No difference in morphology was found between the wild-type strain and the
      ksbA disruptants. However, the ksbA disruptants started producing bafilomycin 18
      h earlier than the wild-type strain and showed a 2.4-fold-higher accumulation of
      bafilomycin. The phenotype was restored to the original wild-type phenotype by
      complementation with intact ksbA, indicating that the autoregulator receptor
      protein of K. setae acts as a primary negative regulator of the biosynthesis of
      bafilomycin but plays no role in cytodifferentiation of K. setae. This indicates
      that, unlike the A-factor receptor of Streptomyces griseus, the autoregulator
      receptor (ksbA) of K. setae belongs to a family of autoregulator receptors which
      control secondary metabolism but play no role in morphological differentiation.

PMID- 15150229
TI  - Two oligopeptide-permease-encoding genes in the clavulanic acid cluster of
      Streptomyces clavuligerus are essential for production of the beta-lactamase
      inhibitor.
AB  - orf7 (oppA1) and orf15 (oppA2) are located 8 kb apart in the clavulanic acid gene
      cluster of Streptomyces clavuligerus and encode proteins which are 48.0%
      identical. These proteins show sequence similarity to periplasmic oligopeptide
      binding proteins. Mutant S. clavuligerus oppA1::acc, disrupted in oppA1, lacks
      clavulanic acid production. Clavulanic acid production is restored by
      transformation with plasmid pIJ699-oppA1, which carries oppA1, but not with the
      multicopy plasmid pIJ699-oppA2, which carries oppA2. The mutant S. clavuligerus
      oppA2::aph also lacks clavulanic acid production, shows a bald phenotype, and
      overproduces holomycin (5). Clavulanic acid production at low levels is restored
      in the oppA2-disrupted mutants by transformation with plasmid pIJ699-oppA2, but
      it is not complemented by the multicopy plasmid pIJ699-oppA1. Both genes encode
      oligopeptide permeases with different substrate specificities. The disrupted S.
      clavuligerus oppA2::aph is not able to grow on RPPGFSPFR (Arg-Pro-Pro-Gly-Phe-Ser
      Pro-Phe-Arg; bradykinin), but both mutants grow on VAPG (Val-Ala-Pro-Gly) as the
      only nitrogen source, indicating differences in the peptide bound by the proteins
      encoded by both genes. The null S. clavuligerus oppA1::acc and S. clavuligerus
      oppA2::aph mutants are more resistant to the toxic tripeptide phosphinothricyl
      alanyl-alanine (also named bialaphos) than the wild-type strain, suggesting that
      this peptide might be transported by these peptide-binding proteins.

PMID- 15150230
TI  - The davDT operon of Pseudomonas putida, involved in lysine catabolism, is induced
      in response to the pathway intermediate delta-aminovaleric acid.
AB  - Pseudomonas putida KT2440 is a soil microorganism that attaches to seeds and
      efficiently colonizes the plant's rhizosphere. Lysine is one of the major
      compounds in root exudates, and P. putida KT2440 uses this amino acid as a source
      of carbon, nitrogen, and energy. Lysine is channeled to delta-aminovaleric acid
      and then further degraded to glutaric acid via the action of the davDT gene
      products. We show that the davDT genes form an operon transcribed from a single
      sigma70-dependent promoter. The relatively high level of basal expression from
      the davD promoter increased about fourfold in response to the addition of
      exogenous lysine to the culture medium. However, the true inducer of this operon
      seems to be delta-aminovaleric acid because in a mutant unable to metabolize
      lysine to delta-aminovaleric acid, this compound, but not lysine, acted as an
      effector. Effective induction of the P. putida P(davD) promoter by exogenously
      added lysine requires efficient uptake of this amino acid, which seems to proceed
      by at least two uptake systems for basic amino acids that belong to the
      superfamily of ABC transporters. Mutants in these ABC uptake systems retained
      basal expression from the davD promoter but exhibited lower induction levels in
      response to exogenous lysine than the wild-type strain.

PMID- 15150231
TI  - Single-step capsular transformation and acquisition of penicillin resistance in
      Streptococcus pneumoniae.
AB  - The capsule (cps) locus of Streptococcus pneumoniae is flanked by the pbp2x and
      pbp1a genes, coding for penicillin-binding proteins, enzymes involved in cell
      wall synthesis that are targets for beta-lactams. This linkage suggested to us
      that selection for beta-lactam resistance might coselect for capsular
      transformants. The recombination event would then involve PBP genes, as well as
      the cps operon, and would change both the serotype and the resistance profile of
      the strain. We transformed beta-lactam-susceptible strain TIGR4 by using whole
      genomic DNA extracted from multidrug-resistant strain GA71, a serotype 19F
      variant of pneumococcal clone Spain(23F)-1, and selected beta-lactam-resistant
      transformants. Smooth colonies appearing on selective plates were subcultured,
      serotyped by the Quellung reaction, and genotyped to confirm the presence of the
      GA71 pbp2x-cps19-pbp1a locus in the TIGR4 genetic background by restriction
      fragment length polymorphism analysis of the whole locus and its flanking
      regions. The results showed that a new serotype, combined with resistance to beta
      lactams, could emerge in a susceptible strain via a single transformation event.
      Quantitative analysis showed that transfer of the cps locus had occurred at an
      elevated rate in beta-lactam-selected transformants. This suggests that in
      natural settings selection by host immunity and selection by antibiotics may be
      interrelated because of "hitchhiking" effects due to linkage of resistance
      determinants and the capsule locus.

PMID- 15150232
TI  - Identification and characterization of glxR, a gene involved in regulation of
      glyoxylate bypass in Corynebacterium glutamicum.
AB  - A corynebacterial clone, previously isolated by scoring repression of lacZYA
      fused to the aceB promoter of Corynebacterium glutamicum, was analyzed further.
      In the clone, an open reading frame designated glxR, consisting of 681
      nucleotides and encoding a 24,957-Da protein, was found. The molecular mass of a
      native GlxR protein was estimated by gel filtration column chromatography to be
      44,000 Da, suggesting that the protein formed dimers. The predicted amino acid
      sequence contained both cyclic AMP (cAMP)- and DNA-binding motifs and was
      homologous with the cAMP receptor protein family of proteins. The aceB-repressing
      activity of the glxR clone was markedly relieved in an Escherichia coli cya
      mutant, but the activity was restored in growth medium containing cAMP. In
      glucose medium, the intracellular cAMP concentration of C. glutamicum reached 22
      nmol/mg of protein in the early exponential phase and then decreased further; but
      in acetate medium, the intracellular cAMP concentration was only 5 nmol/mg of
      protein and remained low throughout the growth phase. The expression of glxR was
      not affected by the carbon source. Binding of purified GlxR to the promoter
      region of aceB could be demonstrated only in the presence of cAMP. These data
      suggest that GlxR may form dimers which bind to the aceB promoter region in the
      presence of cAMP and repress the glyoxylate bypass genes.

PMID- 15150233
TI  - nsd, a locus that affects the Myxococcus xanthus cellular response to nutrient
      concentration.
AB  - Expression of the previously reported Tn5lac Omega4469 insertion in Myxococcus
      xanthus cells is regulated by the starvation response. Interested in learning
      more about the starvation response, we cloned and sequenced the region containing
      the insertion. Our analysis shows that the gene fusion is located in an open
      reading frame that we have designated nsd (nutrient sensing/utilizing defective)
      and that its expression is driven by a sigma70-like promoter. Sequence analysis
      of the nsd gene product provides no information on the potential structure or
      function of the encoded protein. In a further effort to learn about the role of
      nsd in the starvation response, we closely examined the phenotype of cells
      carrying the nsd::Tn5lac Omega4469 mutation. Our analysis showed that these cells
      initiate development on medium that contains nutrients sufficient to sustain
      vegetative growth of wild-type cells. Furthermore, in liquid media these same
      nutrient concentrations elicit a severe impairment of growth of nsd cells. The
      data suggest that the nsd cells launch a starvation response when there are
      enough nutrients to prevent one. In support of this hypothesis, we found that,
      when grown in these nutrient concentrations, nsd cells accumulate guanosine
      tetraphosphate, the cellular starvation signal. Therefore, we propose that nsd is
      used by cells to respond to available nutrient levels.

PMID- 15150235
TI  - Bacteriophage Tuc2009 encodes a tail-associated cell wall-degrading activity.
AB  - Tuc2009 is a P335-type member of the tailed-phage supergroup Siphoviridae and was
      originally identified as a resident prophage of the gram-positive bacterium
      Lactococcus lactis UC509. A Tuc2009 gene designated tal2009 which is located
      within the morphogenic module was shown to specify a lytic activity within the 3'
      portion of its coding region. Comparative sequence analysis indicated that the
      cell wall-degrading part of Tal2009 is a member of the M37 protein family and
      that Tal2009 lacks a cell-binding domain, a finding supported by binding studies.
      Tal2009 appears to undergo self-mediated posttranslational processing in both L.
      lactis and Escherichia coli. Antibodies directed against a purified C-terminal
      portion of Tal2009 were used for immunoelectron microscopy, which showed that
      Tal2009 is located at the tail tip of Tuc2009. Antibody neutralization studies
      demonstrated that Tal2009-directed antibodies inhibited the ability of phage to
      mediate host lysis by more than 100-fold. These data indicate that tal2009
      encodes a tail-associated lysin involved in localized cell wall degradation, thus
      allowing the Tuc2009 DNA injection machinery access to the membrane of its
      bacterial host.

PMID- 15150234
TI  - Characterization of a eukaryotic-like tyrosine protein kinase expressed by the
      Shiga toxin-encoding bacteriophage 933W.
AB  - The Shiga toxin (Stx)-encoding bacteriophage 933W contains an open reading frame,
      stk, with amino acid sequence similarity to the catalytic domain of eukaryotic
      serine/threonine (Ser/Thr) protein kinases (PKs). Eukaryotic PKs are related by a
      common catalytic domain, consisting of invariant and nearly invariant residues
      necessary for ATP binding and phosphotransfer. We demonstrate that rather than a
      Ser/Thr kinase, stk encodes a eukaryotic-like tyrosine (Tyr) kinase. An affinity
      purified recombinant Stk (rStk) autophosphorylates and catalyzes the
      phosphorylation of an artificial substrate on Tyr residues and not on Ser or Thr
      residues. A change of an invariant lysine within the putative catalytic domain
      abolishes this kinase activity, indicating that Stk uses a phosphotransfer
      mechanism similar to the mechanism used by eukaryotic PKs. We provide evidence
      suggesting that stk is cotranscribed with cI from the phage promoter responsible
      for maintaining CI expression during lysogeny. The stk gene was identified in
      prophages obtained from independently isolated Stx-producing Escherichia coli
      clinical isolates, suggesting that selective pressure has maintained the stk gene
      in these pathogenic bacteria.

PMID- 15150236
TI  - Transcription by an archaeal RNA polymerase is slowed but not blocked by an
      archaeal nucleosome.
AB  - Archaeal RNA polymerases (RNAPs) are closely related to eukaryotic RNAPs, and in
      Euryarchaea, genomic DNA is wrapped and compacted by histones into archaeal
      nucleosomes. In eukaryotes, transcription of DNA bound into nucleosomes is
      facilitated by histone tail modifications and chromatin remodeling complexes, but
      archaeal histones do not have histone tails and archaeal genome sequences provide
      no evidence for archaeal homologs of eukaryotic chromatin remodeling complexes.
      We have therefore investigated the ability of an archaeal RNAP, purified from
      Methanothermobacter thermautotrophicus, to transcribe DNA bound into an archaeal
      nucleosome by HMtA2, an archaeal histone from M. thermautotrophicus. To do so, we
      constructed a template that allows transcript elongation to be separated from
      transcription initiation, on which archaeal nucleosome assembly is positioned
      downstream from the site of transcription initiation. At 58 degrees C, in the
      absence of an archaeal nucleosome, M. thermautotrophicus RNAP transcribed this
      template DNA at a rate of approximately 20 nucleotides per second. With an
      archaeal nucleosome present, transcript elongation was slowed but not blocked,
      with transcription pausing at sites before and within the archaeal nucleosome.
      With additional HMtA2 binding, complexes were obtained that also incorporated the
      upstream regulatory region. This inhibited transcription presumably by preventing
      archaeal TATA-box binding protein, general transcription factor TFB, and RNAP
      access and thus inhibiting transcription initiation.

PMID- 15150237
TI  - Purification and characterization of the AAA+ domain of Sinorhizobium meliloti
      DctD, a sigma54-dependent transcriptional activator.
AB  - Activators of sigma54-RNA polymerase holoenzyme couple ATP hydrolysis to
      formation of an open complex between the promoter and RNA polymerase. These
      activators are modular, consisting of an N-terminal regulatory domain, a C
      terminal DNA-binding domain, and a central activation domain belonging to the
      AAA+ superfamily of ATPases. The AAA+ domain of Sinorhizobium meliloti C4
      dicarboxylic acid transport protein D (DctD) is sufficient to activate
      transcription. Deletion analysis of the 3' end of dctD identified the minimal
      functional C-terminal boundary of the AAA+ domain of DctD as being located
      between Gly-381 and Ala-384. Histidine-tagged versions of the DctD AAA+ domain
      were purified and characterized. The DctD AAA+ domain was significantly more
      soluble than DctD(Delta(1-142)), a truncated DctD protein consisting of the AAA+
      and DNA-binding domains. In addition, the DctD AAA+ domain was more homogeneous
      than DctD(Delta(1-142)) when analyzed by native gel electrophoresis, migrating
      predominantly as a single high-molecular-weight species, while DctD(Delta(1-142))
      displayed multiple species. The DctD AAA+ domain, but not DctD(Delta(1-142)),
      formed a stable complex with sigma54 in the presence of the ATP transition state
      analogue ADP-aluminum fluoride. The DctD AAA+ domain activated transcription in
      vitro, but many of the transcripts appeared to terminate prematurely, suggesting
      that the DctD AAA+ domain interfered with transcription elongation. Thus, the DNA
      binding domain of DctD appears to have roles in controlling the oligomerization
      of the AAA+ domain and modulating interactions with sigma54 in addition to its
      role in recognition of upstream activation sequences.

PMID- 15150238
TI  - Interaction of the sliding clamp beta-subunit and Hda, a DnaA-related protein.
AB  - In Escherichia coli, interactions between the replication initiation protein
      DnaA, the beta subunit of DNA polymerase III (the sliding clamp protein), and
      Hda, the recently identified DnaA-related protein, are required to convert the
      active ATP-bound form of DnaA to an inactive ADP-bound form through the
      accelerated hydrolysis of ATP. This rapid hydrolysis of ATP is proposed to be the
      main mechanism that blocks multiple initiations during cell cycle and acts as a
      molecular switch from initiation to replication. However, the biochemical
      mechanism for this crucial step in DNA synthesis has not been resolved. Using
      purified Hda and beta proteins in a plate binding assay and Ni-nitrilotriacetic
      acid pulldown analysis, we show for the first time that Hda directly interacts
      with beta in vitro. A new beta-binding motif, a hexapeptide with the consensus
      sequence QL[SP]LPL, related to the previously identified beta-binding
      pentapeptide motif (QL[SD]LF) was found in the amino terminus of the Hda protein.
      Mutants of Hda with amino acid changes in the hexapeptide motif are severely
      defective in their ability to bind beta. A 10-amino-acid peptide containing the
      E. coli Hda beta-binding motif was shown to compete with Hda for binding to beta
      in an Hda-beta interaction assay. These results establish that the interaction of
      Hda with beta is mediated through the hexapeptide sequence. We propose that this
      interaction may be crucial to the events that lead to the inactivation of DnaA
      and the prevention of excess initiation of rounds of replication.

PMID- 15150239
TI  - Transcriptome analysis of Crp-dependent catabolite control of gene expression in
      Escherichia coli.
AB  - We report here the transcriptome analyses of highly expressed genes that are
      subject to catabolite repression or activation mediated by the cyclic AMP
      receptor protein (Crp). The results reveal that many operons encoding enzymes of
      central carbon metabolic pathways (e.g., Krebs cycle enzymes), as well as
      transporters and enzymes that initiate carbon metabolism, are subject to direct
      Crp-mediated catabolite repression. By contrast, few enzyme-encoding genes
      (direct regulation) but many ribosomal protein- and tRNA-encoding genes (indirect
      regulation) are subject to Crp-dependent glucose activation. Additionally, Crp
      mediates strong indirect catabolite repression of many cytoplasmic stress
      response proteins, including the major chaperone proteins, five ATP-dependent
      protease complexes, and several cold and heat shock proteins. These results were
      confirmed by (i) phenotypic analyses, (ii) real-time PCR studies, (iii) reporter
      gene fusion assays, and (iv) previously published reports about representative
      genes. The results serve to define and extend our appreciation of the Crp
      regulon.

PMID- 15150240
TI  - Structure of the DNA-SspC complex: implications for DNA packaging, protection,
      and repair in bacterial spores.
AB  - Bacterial spores have long been recognized as the sturdiest known life forms on
      earth, revealing extraordinary resistance to a broad range of environmental
      assaults. A family of highly conserved spore-specific DNA-binding proteins,
      termed alpha/beta-type small, acid-soluble spore proteins (SASP), plays a major
      role in mediating spore resistance. The mechanism by which these proteins exert
      their protective activity remains poorly understood, in part due to the lack of
      structural data on the DNA-SASP complex. By using cryoelectron microscopy, we
      have determined the structure of the helical complex formed between DNA and SspC,
      a characteristic member of the alpha/beta-type SASP family. The protein is found
      to fully coat the DNA, forming distinct protruding domains, and to modify DNA
      structure such that it adopts a 3.2-nm pitch. The protruding SspC motifs allow
      for interdigitation of adjacent DNA-SspC filaments into a tightly packed assembly
      of nucleoprotein helices. By effectively sequestering DNA molecules, this dense
      assembly of filaments is proposed to enhance and complement DNA protection
      obtained by DNA saturation with the alpha/beta-type SASP.

PMID- 15150241
TI  - Distinct mutations in PlcR explain why some strains of the Bacillus cereus group
      are nonhemolytic.
AB  - Bacillus thuringiensis, Bacillus cereus, and Bacillus anthracis are closely
      related species belonging to the Bacillus cereus group. B. thuringiensis and B.
      cereus generally produce extracellular proteins, including phospholipases and
      hemolysins. Transcription of the genes encoding these factors is controlled by
      the pleiotropic regulator PlcR. Disruption of plcR in B. cereus and B.
      thuringiensis drastically reduces the hemolytic, lecithinase, and cytotoxic
      properties of these organisms. B. anthracis does not produce these proteins due
      to a nonsense mutation in the plcR gene. We screened 400 B. thuringiensis and B.
      cereus strains for their hemolytic and lecithinase properties. Eight Hly- Lec-
      strains were selected and analyzed to determine whether this unusual phenotype
      was due to a mutation similar to that found in B. anthracis. Sequence analysis of
      the DNA region including the plcR and papR genes of these strains and genetic
      complementation of the strains with functional copies of plcR and papR indicated
      that different types of mutations were responsible for these phenotypes. We also
      found that the plcR genes of three B. anthracis strains belonging to different
      phylogenetic groups contained the same nonsense mutation, suggesting that this
      mutation is a distinctive trait of this species.

PMID- 15150242
TI  - Evidence for an arginine exporter encoded by yggA (argO) that is regulated by the
      LysR-type transcriptional regulator ArgP in Escherichia coli.
AB  - The anonymous open reading frame yggA of Escherichia coli was identified in this
      study as a gene that is under the transcriptional control of argP (previously
      called iciA), which encodes a LysR-type transcriptional regulator protein.
      Strains with null mutations in either yggA or argP were supersensitive to the
      arginine analog canavanine, and yggA-lac expression in vivo exhibited argP(+)
      dependent induction by arginine. Lysine supplementation phenocopied the argP null
      mutation in that it virtually abolished yggA expression, even in the argP+
      strain. The dipeptides arginylalanine and lysylalanine behaved much like arginine
      and lysine, respectively, to induce and to turn off yggA transcription. Dominant
      missense mutations in argP (argPd) that conferred canavanine resistance and
      rendered yggA-lac expression constitutive were obtained. The protein deduced to
      be encoded by yggA shares similarity with a basic amino acid exporter (LysE) of
      Corynebacterium glutamicum, and we obtained evidence for increased arginine
      efflux from E. coli strains with either the argPd mutation or multicopy yggA+.
      The null yggA mutation abolished the increased arginine efflux from the argPd
      strain. Our results suggest that yggA encodes an ArgP-regulated arginine
      exporter, and we have accordingly renamed it argO (for "arginine outward
      transport"). We propose that the physiological function of argO may be either to
      prevent the accumulation to toxic levels of canavanine (which is a plant-derived
      antimetabolite) or arginine or to maintain an appropriate balance between the
      intracellular lysine and arginine concentrations.

PMID- 15150243
TI  - The ETT2 gene cluster, encoding a second type III secretion system from
      Escherichia coli, is present in the majority of strains but has undergone
      widespread mutational attrition.
AB  - ETT2 is a second cryptic type III secretion system in Escherichia coli which was
      first discovered through the analysis of genome sequences of enterohemorrhagic E.
      coli O157:H7. Comparative analyses of Escherichia and Shigella genome sequences
      revealed that the ETT2 gene cluster is larger than was previously thought,
      encompassing homologues of genes from the Spi-1, Spi-2, and Spi-3 Salmonella
      pathogenicity islands. ETT2-associated genes, including regulators and
      chaperones, were found at the same chromosomal location in the majority of genome
      sequenced strains, including the laboratory strain K-12. Using a PCR-based
      approach, we constructed a complete tiling path through the ETT2 gene cluster for
      79 strains, including the well-characterized E. coli reference collection
      supplemented with additional pathotypes. The ETT2 gene cluster was found to be
      present in whole or in part in the majority of E. coli strains, whether
      pathogenic or commensal, with patterns of distribution and deletion mirroring the
      known phylogenetic structure of the species. In almost all strains, including
      enterohemorrhagic E. coli O157:H7, ETT2 has been subjected to varying degrees of
      mutational attrition that render it unable to encode a functioning secretion
      system. A second type III secretion system-associated locus that likely encodes
      the ETT2 translocation apparatus was found in some E. coli strains. Intact
      versions of both ETT2-related clusters are apparently present in
      enteroaggregative E. coli strain O42.

PMID- 15150245
TI  - Novel genes that influence development in Streptomyces coelicolor.
AB  - Filamentous soil bacteria of the genus Streptomyces carry out complex
      developmental cycles that result in sporulation and production of numerous
      secondary metabolites with pharmaceutically important activities. To further
      characterize the molecular basis of these developmental events, we screened for
      mutants of Streptomyces coelicolor that exhibit aberrant morphological
      differentiation and/or secondary metabolite production. On the basis of this
      screening analysis and the subsequent complementation analysis of the mutants
      obtained we assigned developmental roles to a gene involved in methionine
      biosynthesis (metH) and two previously uncharacterized genes (SCO6938 and
      SCO2525) and we reidentified two previously described developmental genes (bldA
      and bldM). In contrast to most previously studied genes involved in development,
      the genes newly identified in the present study all appear to encode biosynthetic
      enzymes instead of regulatory proteins. The MetH methionine synthase appears to
      be required for conversion of aerial hyphae into chains of spores, SCO6938 is a
      probable acyl coenzyme A dehydrogenase that contributes to the proper timing of
      aerial mycelium formation and antibiotic production, and SCO2525 is a putative
      methyltransferase that influences various aspects of colony growth and
      development.

PMID- 15150244
TI  - The essential nature of the ubiquitous 26-kilobase circular replicon of Borrelia
      burgdorferi.
AB  - The genome of the type strain (B31) of Borrelia burgdorferi, the causative agent
      of Lyme disease, is composed of 12 linear and 9 circular plasmids and a linear
      chromosome. Plasmid content can vary among strains, but one 26-kb circular
      plasmid (cp26) is always present. The ubiquitous nature of cp26 suggests that it
      provides functions required for bacterial viability. We tested this hypothesis by
      attempting to selectively displace cp26 with an incompatible but replication
      proficient vector, pBSV26. While pBSV26 transformants contained this incompatible
      vector, the vector coexisted with cp26, which is consistent with the hypothesis
      that cp26 carries essential genes. Several cp26 genes with ascribed or predicted
      functions may be essential. These include the BBB29 gene, which has sequence
      homology to a gene encoding a glucose-specific phosphotransferase system
      component, and the resT gene, which encodes a telomere resolvase involved in
      resolution of the replicated telomeres of the linear chromosome and plasmids. The
      BBB29 gene was successfully inactivated by allelic exchange, but attempted
      inactivation of resT resulted in merodiploid transformants, suggesting that resT
      is required for B. burgdorferi growth. To determine if resT is the only cp26 gene
      essential for growth, we introduced resT into B. burgdorferi on pBSV26. This did
      not result in displacement of cp26, suggesting that additional cp26 genes encode
      vital functions. We concluded that B. burgdorferi plasmid cp26 encodes functions
      critical for survival and thus shares some features with the chromosome.

PMID- 15150246
TI  - Recognition of ferric catecholates by FepA.
AB  - Escherichia coli FepA transports certain catecholate ferric siderophores, but not
      others, nor any noncatecholate compounds. Direct binding and competition
      experiments demonstrated that this selectivity originates during the adsorption
      stage. The synthetic tricatecholate Fe-TRENCAM bound to FepA with 50- to 100-fold
      lower affinity than Fe-enterobactin (FeEnt), despite an identical metal center,
      and Fe-corynebactin only bound at much higher concentrations. Neither Fe
      agrobactin nor ferrichrome bound at all, even at concentrations 10(6)-fold above
      the Kd. Thus, FepA only adsorbs catecholate iron complexes, and it selects FeEnt
      among even its close homologs. We used alanine scanning mutagenesis to study the
      contributions of surface aromatic residues to FeEnt recognition. Although not
      apparent from crystallography, aromatic residues in L3, L5, L7, L8, and L10
      affected FepA's interaction with FeEnt. Among 10 substitutions that eliminated
      aromatic residues, Kd increased as much as 20-fold (Y481A and Y638A) and Km
      increased as much as 400-fold (Y478), showing the importance of aromaticity
      around the pore entrance. Although many mutations equally reduced binding and
      transport, others caused greater deficiencies in the latter. Y638A and Y478A
      increased Km 10- and 200-fold more, respectively, than Kd. N-domain loop
      deletions created the same phenotype: Delta60-67 (in NL1) and Delta98-105 (in
      NL2) increased Kd 10- to 20-fold but raised Km 500- to 700-fold. W101A (in NL2)
      had little effect on Kd but increased Km 1,000-fold. These data suggested that
      the primary role of the N terminus is in ligand uptake. Fluorescence and
      radioisotopic experiments showed biphasic release of FeEnt from FepA. In
      spectroscopic determinations, k(off1) was 0.03/s and k(off2) was 0.003/s.
      However, FepAY272AF329A did not manifest the rapid dissociation phase,
      corroborating the role of aromatic residues in the initial binding of FeEnt.
      Thus, the beta-barrel loops contain the principal ligand recognition
      determinants, and the N-domain loops perform a role in ligand transport.

PMID- 15150247
TI  - Methionine sulfoxide reductase A (MsrA) deficiency affects the survival of
      Mycobacterium smegmatis within macrophages.
AB  - Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme which
      reduces oxidized methionine to methionine. Since oxidation of methionine in
      proteins impairs their function, an absence of MsrA leads to abnormalities in
      different organisms, including alterations in the adherence patterns and in vivo
      survival of certain pathogenic bacteria. To understand the role of MsrA in
      intracellular survival of bacteria, we disrupted the gene encoding MsrA in
      Mycobacterium smegmatis through homologous recombination. The msrA mutant strain
      of M. smegmatis exhibited significantly reduced intracellular survival in murine
      J774A.1 macrophages compared to the survival of its wild-type counterpart.
      Furthermore, immunofluorescence and immunoblotting of phagosomes containing M.
      smegmatis strains revealed that the phagosomes with the msrA mutant strain
      acquired both p67(phox) of phagocyte NADPH oxidase and inducible nitric oxide
      synthase much earlier than the phagosomes with the wild-type strain. In addition,
      the msrA mutant strain of M. smegmatis was observed to be more sensitive to
      hydroperoxides than the wild-type strain was in vitro. These results suggest that
      MsrA plays an important role in both extracellular and intracellular survival of
      M. smegmatis.

PMID- 15150248
TI  - DNA binding regions of Q proteins of phages lambda and phi80.
AB  - Bacteriophage lambda gene Q protein and the related proteins of other lambdoid
      phages are transcription antiterminators that interact both with DNA in the late
      gene promoter segment and with RNA polymerase subunits. Using hybrids between Q
      of lambda and the related Q of phage 80, we characterized elements of both Q and
      DNA that contribute to the DNA binding function. In particular, we found a C
      terminal segment of the protein that is responsible for binding specificity and
      an approximately 15 residue segment on a predicted alpha helix within this
      segment at which alanine substitutions decrease DNA binding. We identified a six
      nucleotide segment located between the -35 and -10 promoter elements that confers
      binding specificity and is the site of point mutants that impair binding, and we
      isolated suppressors in lambda Q that restore binding function by increasing the
      overall binding affinity. We also identified putative zinc finger structures in
      both proteins.

PMID- 15150249
TI  - The Sinorhizobium meliloti fur gene regulates, with dependence on Mn(II),
      transcription of the sitABCD operon, encoding a metal-type transporter.
AB  - Sinorhizobium meliloti is an alpha-proteobacterium able to induce nitrogen-fixing
      nodules on roots of specific legumes. In order to propagate in the soil and for
      successful symbiotic interaction the bacterium needs to sequester metals like
      iron and manganese from its environment. The metal uptake has to be in turn
      tightly regulated to avoid toxic effects. In this report we describe the
      characterization of a chromosomal region of S. meliloti encoding the sitABCD
      operon and the putative regulatory fur gene. It is generally assumed that the
      sitABCD operon encodes a metal-type transporter and that the fur gene is involved
      in iron ion uptake regulation. A constructed S. meliloti sitA deletion mutant was
      found to be growth dependent on Mn(II) and to a lesser degree on Fe(II). The sitA
      promoter was strongly repressed by Mn(II), with dependence on Fur, and moderately
      by Fe(II). Applying a genome-wide S. meliloti microarray it was shown that in the
      fur deletion mutant 23 genes were up-regulated and 10 genes were down-regulated
      when compared to the wild-type strain. Among the up-regulated genes only the
      sitABCD operon could be associated with metal uptake. On the other hand, the
      complete rhbABCDEF operon, which is involved in siderophore synthesis, was
      identified among the down-regulated genes. Thus, in S. meliloti Fur is not a
      global repressor of iron uptake. Under symbiotic conditions the sitA promoter was
      strongly expressed and the S. meliloti sitA mutant exhibited an attenuated
      nitrogen fixation activity resulting in a decreased fresh weight of the host
      plant Medicago sativa.

PMID- 15150251
TI  - A cytochrome P450 involved in the metabolism of abietane diterpenoids by
      Pseudomonas abietaniphila BKME-9.
AB  - Diterpenoids are naturally occurring plant compounds which have pharmaceutical
      properties. We have sequenced a 10.4-kbp extension of the dit cluster in
      Pseudomonas abietaniphila BKME-9, containing genes involved in abietane
      diterpenoid biodegradation. The ditQ gene was found to encode a cytochrome P450
      monooxygenase, P450dit, and to be homologous to the tdtD gene of Pseudomonas
      diterpeniphila A19-6a. Knocking out ditQ had little effect on growth of BKME-9 on
      abietic acid but severely impaired growth on dehydroabietic acid (DhA) and
      palustric acid (PaA), increasing doubling times from 3.8 to 15 h on DhA and from
      5.6 to 18.5 h on PaA. A xylE transcriptional fusion showed that transcription of
      ditQ was induced by a range of diterpenoids. Substrate binding assays of P450dit
      expressed in Escherichia coli revealed that DhA binds to the enzyme and yields a
      type I binding spectrum with a Kd of 0.4 microM. These results indicate that
      P450dit is involved in the metabolism of DhA and PaA and are consistent with its
      putative role in converting DhA to 7-hydroxy-DhA. Finally, an amino acid sequence
      identity of greater than 72% and conserved gene arrangement support the
      hypothesis that the dit gene cluster of P. abietaniphila BKME-9 and the tdt
      cluster of P. diterpeniphila A19-6a contain functional homologues.

PMID- 15150252
TI  - Dimethylselenide demethylation is an adaptive response to selenium deprivation in
      the archaeon Methanococcus voltae.
AB  - The archaeon Methanococcus voltae needs selenium for optimal growth. A gene group
      most likely involved in the demethylation of dimethylselenide was discovered, the
      expression of which is induced upon selenium deprivation. The operon comprises
      open reading frames for a corrinoid protein and two putative methyltransferases.
      It is shown that the addition of dimethylselenide to selenium-depleted growth
      medium relieves the lack of selenium, as indicated by the repression of a
      promoter of a transcription unit encoding selenium-free hydrogenases which is
      normally active only upon selenium deprivation. Knockout mutants of the corrinoid
      protein or one of the two methyltransferase genes did not show repression of the
      hydrogenase promoter in the presence of dimethylselenide. The mutation of the
      other methyltransferase gene had no effect. Growth rates of the two effective
      mutants were reduced compared to wild-type cells in selenium-limited medium in
      the presence of dimethylselenide.

PMID- 15150250
TI  - The Pseudomonas syringae HopPtoV protein is secreted in culture and translocated
      into plant cells via the type III protein secretion system in a manner dependent
      on the ShcV type III chaperone.
AB  - The bacterial plant pathogen Pseudomonas syringae depends on a type III protein
      secretion system and the effector proteins that it translocates into plant cells
      to cause disease and to elicit the defense-associated hypersensitive response on
      resistant plants. The availability of the P. syringae pv. tomato DC3000 genome
      sequence has resulted in the identification of many novel effectors. We
      identified the hopPtoV effector gene on the basis of its location next to a
      candidate type III chaperone (TTC) gene, shcV, and within a pathogenicity island
      in the DC3000 chromosome. A DC3000 mutant lacking ShcV was unable to secrete
      detectable amounts of HopPtoV into culture supernatants or translocate HopPtoV
      into plant cells, based on an assay that tested whether HopPtoV-AvrRpt2 fusions
      were delivered into plant cells. Coimmunoprecipitation and Saccharomyces
      cerevisiae two-hybrid experiments showed that ShcV and HopPtoV interact directly
      with each other. The ShcV binding site was delimited to an N-terminal region of
      HopPtoV between amino acids 76 and 125 of the 391-residue full-length protein.
      Our results demonstrate that ShcV is a TTC for the HopPtoV effector. DC3000
      overexpressing ShcV and HopPtoV and DC3000 mutants lacking either HopPtoV or both
      ShcV and HopPtoV were not significantly impaired in disease symptoms or bacterial
      multiplication in planta, suggesting that HopPtoV plays a subtle role in
      pathogenesis or that other effectors effectively mask the contribution of HopPtoV
      in plant pathogenesis.

PMID- 15150253
TI  - Lactococcal phage genes involved in sensitivity to AbiK and their relation to
      single-strand annealing proteins.
AB  - Lactococcal phage mutants insensitive to the antiviral abortive infection
      mechanism AbiK are divided into two classes. One comprises virulent phages that
      result from DNA exchanges between a virulent phage and the host chromosome. Here,
      we report the analysis of the second class of phage mutants, which are
      insensitive to AbiK as a result of a single nucleotide change causing an amino
      acid substitution. The mutated genes occupy the same position in the various
      lactococcal phage genomes, but the deduced proteins do not share amino acid
      sequence similarity. Four nonsimilar proteins involved in the sensitivity to AbiK
      (Sak) were identified. Two of these Sak proteins are related to Erf and RAD52,
      single-strand annealing proteins involved in homologous recombination.

PMID- 15150254
TI  - The global arginine regulator ArgR controls expression of argF in Pseudomonas
      syringae pv. phaseolicola but is not required for the synthesis of phaseolotoxin
      or for the regulated expression of argK.
AB  - In Pseudomonas syringae pv. phaseolicola the enzyme ornithine
      carbamoyltransferase (OCTase), encoded by argF, is negatively regulated by argR,
      similar to what has been reported for Pseudomonas aeruginosa. However, production
      of the phaseolotoxin-resistant OCTase encoded by argK, synthesis of
      phaseolotoxin, and infectivity for bean pods occur independently of the ArgR
      protein.

PMID- 15150255
TI  - The Butyrivibrio fibrisolvens tet(W) gene is carried on the novel conjugative
      transposon TnB1230, which contains duplicated nitroreductase coding sequences.
AB  - The Butyrivibrio fibrisolvens tet(W) gene is located on the conjugative
      transposon TnB1230. TnB1230 encodes transfer proteins with 48 to 67% identity to
      some of those encoded by Tn1549. tet(W) is flanked by directly repeated sequences
      with significant homology to oxygen-insensitive nitroreductases. The 340
      nucleotides upstream of tet(W) are strongly conserved and are required for
      tetracycline resistance.

PMID- 15150256
TI  - Identification of the two missing bacterial genes involved in thiamine salvage:
      thiamine pyrophosphokinase and thiamine kinase.
AB  - The genes encoding thiamine kinase in Escherichia coli (ycfN) and thiamine
      pyrophosphokinase in Bacillus subtilis (yloS) have been identified. This study
      completes the identification of the thiamine salvage enzymes in bacteria.

PMID- 15150257
TI  - Escherichia coli mazEF-mediated cell death is triggered by various stressful
      conditions.
AB  - mazEF is an Escherichia coli suicide module specific for a stable toxin and a
      labile antitoxin. Inhibiting mazEF expression appeared to activate the module to
      cause cell death. Here we show that several stressful conditions, including high
      temperatures, DNA damage, and oxidative stress, also induce mazEF-mediated cell
      death. We also show that this process takes place only during logarithmic growth
      and requires an intact relA gene.

PMID- 15150258
TI  - Calcium activation of ERK mediated by calmodulin kinase I.
AB  - Elevated intracellular Ca(2+) triggers numerous signaling pathways including
      protein kinases such as the calmodulin-dependent kinases (CaMKs) and the
      extracellular signal-regulated kinases (ERKs). In the present study we examined
      Ca(2+)-dependent "cross-talk" between these two protein kinase families. Using a
      combination of pharmacological inhibitors and dominant-negative kinases
      (dnKinase), we identified a requirement for CaMKK acting through CaMKI in the
      stimulation of ERKs upon depolarization of the neuroblastoma cell line, NG108.
      Depolarization stimulated prolonged ERK and JNK activation that was blocked by
      the CaMKK inhibitor, STO-609; this inhibition of ERK activation by STO-609 was
      rescued by expression of a STO-609-insensitive mutant of CaMKK. However,
      activation of ERK by epidermal growth factor or carbachol were not suppressed by
      inhibition of CaMKK, indicating specificity for this "cross-talk." To identify
      the downstream target of CaMKK that mediated ERK activation upon depolarization,
      dnKinases were expressed. The dnCaMKI completely suppressed ERK2 activation
      whereas dnAKT/PKB or nuclear-targeted dnCaMKIV, other substrates for CaMKK, were
      not inhibitory. ERK activation upon depolarization or transfection with
      constitutively active (ca) CaMKI was blocked by dnRas. Additionally,
      depolarization of NG108 cells promoted neurite outgrowth, and this effect was
      blocked by inhibition of either CaMKK (STO-609) or ERK (UO126). Co-transfection
      with caCaMKK plus caCaMKI also stimulated neurite outgrowth that was blocked by
      inhibition of ERK (UO126). These data are the first to suggest that ERK
      activation and neurite outgrowth in response to depolarization are mediated by
      CaMKK activation of CaMKI.

PMID- 15150260
TI  - The T cell receptor gamma chain alternate reading frame protein (TARP), a
      prostate-specific protein localized in mitochondria.
AB  - We previously showed that mRNA encoding TARP (T cell receptor gamma chain
      alternate reading frame protein) is exclusively expressed in the prostate in
      males and is up-regulated by androgen in LNCaP cells, an androgen-sensitive
      prostate cancer cell line. We have now developed an anti-TARP monoclonal antibody
      named TP1, and show that TARP protein is up-regulated by androgen in both LNCaP
      and MDA-PCa-2b cells. We used TP1 to determine the subcellular localization of
      TARP by Western blotting following subcellular fractionation and
      immunocytochemistry. Both methods showed that TARP is localized in the
      mitochondria of LNCaP cells, MDA-PCa-2b cells, and PC-3 cells transfected with a
      TARP-expressing plasmid. We also transfected a plasmid encoding TARP fused to
      green fluorescent protein into LNCaP, MDA-Pca-2b, and PC-3 cells and confirmed
      its specific mitochondrial localization in living cells. Fractionation of
      mitochondria shows that TARP is located in the outer mitochondrial membrane.
      Immunohistochemistry using a human prostate cancer sample showed that TP1 reacted
      in a dot-like cytoplasmic pattern consistent with the presence of TARP in
      mitochondria. These data demonstrate that TARP is the first prostate-specific
      protein localizing in mitochondria and indicate that TARP, an androgen-regulated
      protein, may act on mitochondria to carry out its biological functions.

PMID- 15150259
TI  - Transcription coactivator PBP, the peroxisome proliferator-activated receptor
      (PPAR)-binding protein, is required for PPARalpha-regulated gene expression in
      liver.
AB  - Nuclear receptor coactivator PBP (peroxisome proliferator-activated receptor
      (PPAR)-binding protein) functions as a coactivator for PPARs and other nuclear
      receptors. PBP serves as an anchor for TRAP (thyroid hormone receptor-associated
      proteins)/mediator multisubunit cofactor transcription complex. Disruption of the
      PBP/TRAP220 gene results in embryonic lethality around embryonic day 11.5 by
      affecting placental, cardiac, hepatic, and bone marrow development. Because PPAR
      isoforms alpha, gamma, and beta/delta function as important regulators of lipid
      homeostasis in mammals, it becomes important to assess the requirement of
      coactivator PBP in the regulation of PPAR functions in vivo. Sustained activation
      of PPARalpha by structurally diverse classes of chemicals of biological
      importance, designated peroxisome proliferators, leads to proliferation of
      peroxisomes in liver, induction of PPARalpha target genes including those
      involved in fatty acid oxidation, and the eventual development of liver tumors.
      Here, we show that targeted deletion of PBP in liver parenchymal cells, using the
      Cre-loxP system, results in the near abrogation of PPARalpha ligand-induced
      peroxisome proliferation and liver cell proliferation, as well as the induction
      of PPARalpha-regulated genes in PBP-deficient liver cells. In contrast, scattered
      PBP(+/+) hepatocytes in these livers showed DNA synthesis and were markedly
      hypertrophic with peroxisome proliferation in response to PPARalpha ligands.
      Chromatin immunoprecipitation data suggest that in PBP conditional null livers,
      there appears to be reduced association of cofactors, especially of CBP and
      TRAP150, to the mouse enoyl-CoA hydratase/l-3-hydroxyacyl-CoA dehydrogenase gene
      promoter. These observations suggest that PBP is required for the stabilization
      of multiprotein cofactor complexes. In essence, the absence of PBP in hepatocytes
      in vivo appears to mimic the absence of PPARalpha, indicating that coactivator
      PBP is essential for PPARalpha-regulated gene expression in liver parenchymal
      cells.

PMID- 15150261
TI  - Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function.
AB  - The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly
      on T cells that is activated by three ligands as follows: CXCL9 (Mig), CXCL10 (IP
      10), and CXCL11 (I-TAC). Previously, we have found that of the three ligands,
      CXCL11 is the most potent inducer of CXCR3 internalization and is the physiologic
      inducer of CXCR3 internalization after T cell contact with activated endothelial
      cells. We have therefore hypothesized that these three ligands transduce
      different signals to CXCR3. In light of this hypothesis, we sought to determine
      whether regions of CXCR3 are differentially required for CXCL9, CXCL10, and
      CXCL11 function. Here we identified two distinct domains that contributed to
      CXCR3 internalization. The carboxyl-terminal domain and beta-arrestin1 were
      predominantly required by CXCL9 and CXCL10, and the third intracellular loop was
      predominantly required by CXCL11. Chemotaxis and calcium mobilization induced by
      all three CXCR3 ligands were dependent on the CXCR3 carboxyl terminus and the DRY
      sequence in the third trans-membrane domain. Our findings demonstrate that
      distinct domains of CXCR3 mediate its functions and suggest that the differential
      requirement of these domains contributes to the complexity of the chemokine
      system.

PMID- 15150262
TI  - Inhibition of RNA polymerase II phosphorylation by a viral interferon antagonist.
AB  - Many viruses subvert the cellular interferon (IFN) system with so-called IFN
      antagonists. Bunyamwera virus (BUNV) belongs to the family Bunyaviridae and is
      transmitted by arthropods. We have recently identified the nonstructural protein
      NSs of BUNV as a virulence factor that inhibits IFN-beta gene expression in the
      mammalian host. Here, we demonstrate that NSs targets the RNA polymerase II (RNAP
      II) complex. The C-terminal domain (CTD) of RNAP II consists of 52 repeats of the
      consensus sequence YSPTSPS. Phosphorylation at serine 5 is required for efficient
      initiation of transcription, and subsequent phosphorylation at serine 2 is
      required for mRNA elongation and 3'-end processing. In BUNV-infected mammalian
      cells, serine 5 phosphorylation occurred normally. Furthermore, RNAP II was able
      to bind to the IFN-beta gene promoter as revealed by chromatin
      immunoprecipitation analysis, indicating that the initiation of transcription was
      not disturbed by NSs. However, NSs prevented CTD phosphorylation at serine 2,
      suggesting a block in transition from initiation to elongation. Surprisingly, no
      interference with CTD phosphorylation was observed in insect cells. Our results
      indicate that BUNV uses an unconventional mechanism to block IFN synthesis in the
      mammalian host by directly dysregulating RNAP II. Moreover, by inducing a general
      transcriptional block, NSs may contribute to the lytic infection observed in
      mammalian cells as opposed to persistent infection in the insect host.

PMID- 15150264
TI  - CCAAT/enhancer-binding protein alpha (C/EBPalpha) activates transcription of the
      human microsomal epoxide hydrolase gene (EPHX1) through the interaction with DNA
      bound NF-Y.
AB  - Microsomal epoxide hydrolase (mEH) plays a central role in xenobiotic metabolism
      as well as mediating the sodium-dependent uptake of bile acids into the liver,
      where these compounds regulate numerous biological processes such as cholesterol
      metabolism and hepatocyte signaling pathways. Little is known, however, about the
      factors that control the constitutive and inducible expression of the mEH gene
      (EPHX1) that is altered during development and in response to numerous
      xenobiotics. In previous studies we have established that GATA-4 binding to the
      EPHX1 core promoter is critical for EPHX1 expression. The -80/+25 bp core
      promoter also contained a reversed CCAAT box (-5/-1 bp), integrity of which was
      required for maximal basal EPHX1 transcription in HepG2 cells. Transient
      transfection of CCAAT/enhancer-binding protein alpha (C/EBPalpha) substantially
      stimulated EPHX1 promoter activity. Electrophoretic mobility shift assays,
      however, revealed that nuclear factor Y (NF-Y), but not C/EBPalpha, directly
      bound to this site although increased expression of NF-Y had no effect on EPHX1
      promoter activity. These results suggested that C/EBPalpha activated EPHX1
      expression through its interaction with NF-Y bound to the CCAAT box. The
      existence of a C/EBPalpha[NF-Y] complex was supported by electrophoretic mobility
      shift assays using antibodies against NF-Y and C/EBPalpha as well as by the
      ability of a dominant-negative NF-Y expression vector to inhibit promoter
      activity. The interaction between these transcription factors was established by
      co-immunoprecipitation analysis and glutathione S-transferase pull-down assays,
      whereas the association of the two factors and the interaction of NF-Y with the
      CCAAT box in vivo was confirmed by chromatin immunoprecipitation assays.
      C/EBPalpha-dependent EPHX1 activation was also supported by reconstitution
      studies in HeLa cells that lack this protein. These results establish that EPHX1
      expression is regulated by C/EBPalpha interacting with DNA-bound NF-Y.

PMID- 15150263
TI  - Subcellular expression of autoimmune regulator is organized in a spatiotemporal
      manner.
AB  - Autoimmune regulator (AIRE) is responsible for the development of organ-specific
      autoimmune disease in a monogenic fashion. Rare and low levels of tissue
      expression together with the lack of AIRE-expressing cell lines have hampered a
      detailed analysis of the molecular dynamics of AIRE. Here we have established
      cell lines stably transfected with AIRE and studied the regulatory mechanisms for
      its subcellular expression. We found that nuclear body (NB) formation by AIRE was
      dependent on the cell cycle. Biochemical fractionation revealed that a
      significant proportion of AIRE is associated with the nuclear matrix, which
      directs the functional domains of chromatin to provide sites for gene regulation.
      Upon proteasome inhibition, AIRE NBs were increased with concomitant reduced
      expression in the cytoplasm, suggesting that subcellular targeting of AIRE is
      regulated by a ubiquitin-proteasome pathway. We also found that AIRE NBs compete
      for cAMP-response element-binding protein-binding protein/p300, a common
      coactivator of transcription, with the promyelocytic leukemia gene product. These
      results suggest that the transcriptional regulating activities of AIRE within a
      cell are controlled and organized in a spatiotemporal manner.

PMID- 15150266
TI  - Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of
      catalytic sites of Escherichia coli F1-ATPase.
AB  - Residues responsible for phosphate binding in F(1)F(0)-ATP synthase catalytic
      sites are of significant interest because phosphate binding is believed linked to
      proton gradient-driven subunit rotation. From x-ray structures, a phosphate
      binding subdomain is evident in catalytic sites, with conserved betaArg-246 in a
      suitable position to bind phosphate. Mutations betaR246Q, betaR246K, and
      betaR246A in Escherichia coli were found to impair oxidative phosphorylation and
      to reduce ATPase activity of purified F(1) by 100-fold. In contrast to wild type,
      ATPase of mutants was not inhibited by MgADP-fluoroaluminate or MgADP
      fluoroscandium, showing the Arg side chain is required for wild-type transition
      state formation. Whereas 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)
      inhibited wild-type ATPase essentially completely, ATPase in mutants was
      inhibited maximally by approximately 50%, although reaction still occurred at
      residue betaTyr-297, proximal to betaArg-246 in the phosphate-binding pocket.
      Inhibition characteristics supported the conclusion that NBD-Cl reacts in betaE
      (empty) catalytic sites, as shown previously by x-ray structure analysis.
      Phosphate protected against NBD-Cl inhibition in wild type but not in mutants.
      The results show that phosphate can bind in the betaE catalytic site of E. coli
      F(1) and that betaArg-246 is an important phosphate-binding residue.

PMID- 15150265
TI  - Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function.
AB  - Checkpoint activation by DNA damage during G(2) prevents activation of cyclin
      B/Cdc2 complexes, and as a consequence, mitotic entry is blocked. Although
      initiation and maintenance of G(2) arrest are known to be regulated by at least
      two distinct signaling pathways, including those of p38MAPK and ataxia
      telangiectasia-mutated (ATM)- and Rad3-related (ATR)-Chk1 in higher eukaryotes,
      the actual number of signaling pathways involved in this regulation is still
      elusive. In the present study, we identified human SAD1 (hsSAD1) by searching a
      sequence data base. The predicted hsSAD1 protein comprises 778 amino acids and
      shares significant homology with the fission yeast Cdr2, a mitosis-regulatory
      kinase, and Caenorhabditis elegans SAD1, a neuronal cell polarity regulator.
      HsSAD1 transcript was expressed ubiquitously with the highest levels of
      expression in brain and testis. HsSAD1 specifically phosphorylated Wee1A, Cdc25
      C, and -B on Ser-642, Ser-216, and Ser-361 in vitro, respectively. Overexpression
      of hsSAD1 resulted in an increased phosphorylation of Cdc25C on Ser-216 in vivo.
      DNA damage induced by UV or methyl methane sulfonate but not by IR enhanced
      endogenous hsSAD1 kinase activity in a caffeine-sensitive manner and caused
      translocation of its protein from cytoplasm to nucleus. Overexpression of wild
      type hsSAD1 induced G(2)/M arrest in HeLa S2 cells. Furthermore, UV-induced
      G(2)/M arrest was partially abrogated by the reduced expression of hsSAD1 using
      small interfering RNA. These results suggest that hsSAD1 acts as checkpoint
      kinase upon DNA damage induced by UV or methyl methane sulfonate. The
      identification of this new kinase suggests the existence of an alternative
      checkpoint pathway other than those of ATR-Chk1 and p38MAPK.

PMID- 15150267
TI  - Directed mutagenesis in region 713-720 of human thyroperoxidase assigns
      713KFPED717 residues as being involved in the B domain of the discontinuous
      immunodominant region recognized by human autoantibodies.
AB  - Autoantibodies (aAbs) to thyroid peroxidase (TPO), the hallmark of autoimmune
      thyroid disease (AITD), recognize conformational epitopes restricted to an
      immunodominant region (IDR), divided into two overlapping domains A and B.
      Despite numerous efforts aimed at localizing the IDR and identifying aAb
      interacting residues on TPO, only two critical amino acids, Lys(713) and
      Tyr(772), have been characterized. Precise and complete delineation of the other
      residues involved in the IDR remains to be defined. By using a recombinant anti
      TPO aAb T13, we demonstrated that four regions on TPO are part of the IDR/B; one
      of them, located between amino acids 713 and 720, is particularly important for
      the binding of sera from patients suffering from AITD. To precisely define
      critical residues implicated in the binding of aAb to human TPO, we used directed
      mutagenesis and expressed the mutants in stably transfected CHO cells. Then we
      assessed the kinetic parameters involved in the interactions between anti-TPO
      aAbs and mutants by real-time analysis. We identified (i) the minimal epitope 713
      717 recognized by mAb 47 (a reference antibody) and (ii) the amino acids used as
      contact points for two IDR-specific human monoclonal aAbs TR1.9 (Pro(715) and
      Asp(717)) and T13 (Lys(713), Phe(714), Pro(715), and Glu(716)). Using a rational
      strategy to identify complex epitopes on proteins showing a highly convoluted
      architecture, this study definitively identifies the amino acids Lys(713)
      Asp(717) as being the key residues recognized by IDR/B-specific anti-TPO aAbs in
      AITD.

PMID- 15150268
TI  - Evolutionary links as revealed by the structure of Thermotoga maritima S
      adenosylmethionine decarboxylase.
AB  - S-adenosylmethionine decarboxylase (AdoMetDC) is a critical regulatory enzyme of
      the polyamine biosynthetic pathway and belongs to a small class of pyruvoyl
      dependent amino acid decarboxylases. Structural elucidation of the prokaryotic
      AdoMetDC is of substantial interest in order to determine the relationship
      between the eukaryotic and prokaryotic forms of the enzyme. Although both forms
      utilize pyruvoyl groups, there is no detectable sequence similarity except at the
      site of pyruvoyl group formation. The x-ray structure of the Thermatoga maritima
      AdoMetDC proenzyme reveals a dimeric protein fold that is remarkably similar to
      the eukaryotic AdoMetDC protomer, suggesting an evolutionary link between the two
      forms of the enzyme. Three key active site residues (Ser55, His68, and Cys83)
      involved in substrate binding, catalysis or proenzyme processing that were
      identified in the human and potato AdoMet-DCs are structurally conserved in the
      T. maritima AdoMetDC despite very limited primary sequence identity. The role of
      Ser55, His68, and Cys83 in the self-processing reaction was investigated through
      site-directed mutagenesis. A homology model for the Escherichia coli AdoMetDC was
      generated based on the structures of the T. maritima and human AdoMetDCs.

PMID- 15150269
TI  - Identification of functional residues on Caenorhabditis elegans actin-interacting
      protein 1 (UNC-78) for disassembly of actin depolymerizing factor/cofilin-bound
      actin filaments.
AB  - Actin-interacting protein 1 (AIP1) is a WD40 repeat protein that enhances actin
      filament disassembly in the presence of actin-depolymerizing factor
      (ADF)/cofilin. AIP1 also caps the barbed end of ADF/cofilin-bound actin filament.
      However, the mechanism by which AIP1 interacts with ADF/cofilin and actin is not
      clearly understood. We determined the crystal structure of Caenorhabditis elegans
      AIP1 (UNC-78), which revealed 14 WD40 modules arranged in two seven-bladed beta
      propeller domains. The structure allowed for the mapping of conserved surface
      residues, and mutagenesis studies identified five residues that affected the
      ADF/cofilin-dependent actin filament disassembly activity. Mutations of these
      residues, which reside in blades 3 and 4 in the N-terminal propeller domain, had
      significant effects on the disassembly activity but did not alter the barbed end
      capping activity. These data support a model in which this conserved surface of
      AIP1 plays a direct role in enhancing fragmentation/depolymerization of
      ADF/cofilin-bound actin filaments but not in barbed end capping.

PMID- 15150270
TI  - Ca2+ occlusion and gating function of Glu309 in the ADP-fluoroaluminate analog of
      the Ca2+-ATPase phosphoenzyme intermediate.
AB  - In the absence of ATP the sarcoplasmic reticulum ATPase (SERCA) binds two Ca(2+)
      with high affinity. The two bound Ca(2+) rapidly undergo reverse dissociation
      upon addition of EGTA, but can be distinguished by isotopic exchange indicating
      fast exchange at a superficial site (site II), and retardation of exchange at a
      deeper site (site I) by occupancy of site II. Site II mutations that allow high
      affinity binding to site I, but only low affinity binding to site II, show that
      retardation of isotopic exchange requires higher Ca(2+) concentrations with the
      N796A mutant, and is not observed with the E309Q mutant even at millimolar
      Ca(2+). Fluoroaluminate forms a complex at the catalytic site yielding stable
      analogs of the phosphoenzyme intermediate, with properties similar to E2-P or E1
      P.Ca(2). Mutational analysis indicates that Asp(351), Lys(352), Thr(353),
      Asp(703), Asn(706), Asp(707), Thr(625), and Lys(684) participate in stabilization
      of fluoroaluminate and Mg(2+) at the phosphorylation site. In the presence of
      fluoroaluminate and Ca(2+), ADP (or AMP-PCP) favors formation of a stable ADP.E1
      P.Ca(2) analog. This produces strong occlusion of Ca(2+) bound to both sites (I
      and II), whereby dissociation occurs very slowly even following addition of EGTA.
      Occlusion by fluoraluminate and ADP is not observed with the E309Q mutant,
      suggesting a gating function of Glu(309) at the mouth of a binding cavity with a
      single path of entry. This phenomenon corresponds to the earliest step of the
      catalytic cycle following utilization of ATP. Experiments on limited proteolysis
      reveal that a long range conformational change, involving displacement of
      headpiece domains and transmembrane helices, plays a mechanistic role.

PMID- 15150271
TI  - Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of
      rapamycin (mTOR)-independent.
AB  - Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome with
      manifestations that can include seizures, mental retardation, autism, and tumors
      in the brain, retina, kidney, heart, and skin. The products of the TSC1 and TSC2
      genes, hamartin and tuberin, respectively, heterodimerize and inhibit the
      mammalian target of rapamycin (mTOR). We found that tuberin expression increases
      p42/44 MAPK phosphorylation and B-Raf kinase activity. Short interfering RNA down
      regulation of tuberin decreased the p42/44 MAPK phosphorylation and B-Raf
      activity. Expression of Rheb, the target of the GTPase-activating domain of
      tuberin, inhibited wild-type B-Raf kinase but not activated forms of B-Raf. The
      interaction of endogenous Rheb with B-Raf was enhanced by serum and by Ras
      overexpression. A farnesylation-defective mutant of Rheb co-immunoprecipitated
      with and inhibited B-Raf but did not activate ribosomal protein S6 kinase,
      indicating that farnesylation is not required for B-Raf inhibition by Rheb and
      that B-Raf inhibition and S6 kinase activation are separable activities of Rheb.
      Consistent with this, inhibition of B-Raf and p42/44 MAPK by Rheb was resistant
      to rapamycin in contrast to Rheb activation of S6 kinase, which is rapamycin
      sensitive. Taken together these data demonstrate that inhibition of B-Raf kinase
      via Rheb is an mTOR-independent function of tuberin.

PMID- 15150272
TI  - Engagement of protein kinase C-theta in interferon signaling in T-cells.
AB  - Protein kinase C-theta (PKC-theta) plays important roles in the activation and
      survival of lymphocytes and is the predominant PKC isoform expressed in T-cells.
      Interferons regulate T-cell function and activation, but the precise signaling
      mechanisms by which they mediate such effects have not been elucidated. We
      determined whether PKC-theta is engaged in interferon (INF) signaling in T-cells.
      Both Type I (alpha, beta) and Type II (gamma) IFNs induced phosphorylation of PKC
      theta in human T-cell lines and primary human T-lymphocytes. Such phosphorylation
      of PKC-theta resulted in activation of its kinase domain, suggesting that this
      kinase plays a functional role in interferon signaling. Consistent with this,
      inhibition of PKC-theta protein expression using small interfering RNAs (siRNA)
      abrogated IFN-alpha- and IFN-gamma-dependent gene transcription via GAS elements.
      Similarly, blocking of PKC-theta kinase activity by overexpression of a dominant
      negative PKC-theta mutant also blocked GAS-driven transcription, further
      demonstrating a requirement for PKC-theta in IFN-dependent transcriptional
      activation. The effects of PKC-theta on IFN-dependent gene transcription were not
      mediated by regulation of the IFN-activated STAT pathway, as siRNA-mediated PKC
      theta knockdown had no effects on STAT1 phosphorylation and binding of STAT1
      containing complexes to SIE/GAS elements. On the other hand, siRNA-mediated PKC
      theta inhibition blocked phosphorylation/activation of MKK4, suggesting that
      interferon-dependent PKC-theta activation regulates downstream engagement of MAP
      kinase pathways. Altogether, these findings demonstrate that PKC-theta is an
      interferon-inducible kinase and strongly suggest that it plays an important role
      in the generation of interferon-responses in T-cells.

PMID- 15150273
TI  - Menin is required for bone morphogenetic protein 2- and transforming growth
      factor beta-regulated osteoblastic differentiation through interaction with Smads
      and Runx2.
AB  - Menin, the product of the multiple endocrine neoplasia type 1 (MEN1) gene, is
      required for commitment of multipotential mesenchymal stem cells to the
      osteoblast lineage, however, it inhibits their later differentiation (Sowa, H.,
      Kaji, H., Canaff, L., Hendy, G.N., Tsukamoto, T., Yamaguchi, T., Miyazono, K.,
      Sugimoto, T., and Chihara, K. (2003) J. Biol. Chem. 278, 21058-21069). Here, we
      have examined the mechanism of action of menin in regulating osteoblast
      differentiation using the mouse bone marrow stromal ST2 and osteoblast MC3T3-E1
      cell lines. In ST2 cells, reduced menin expression achieved by transfection of
      menin antisense DNA (AS) antagonized bone morphogenetic protein (BMP)-2-induced
      alkaline phosphatase activity and osteocalcin and Runx2 mRNA expression. Menin
      was co-immunoprecipitated with Smad1/5 in ST2 and MC3T3-E1 cells, and
      inactivation of menin antagonized BMP-2-induced transcriptional activity of
      Smad1/5 in ST2 cells, but not MC3T3-E1 cells. Menin was co-immunoprecipitated
      with the key osteoblast regulator, Runx2, and AS antagonized Runx2
      transcriptional activity and the ability of Runx2 to stimulate alkaline
      phosphatase activity only in ST2 cells but not in MC3T3-E1 cells. In the
      osteoblast MC3T3-E1 cells, transforming growth factor-beta and its signaling
      molecule, Smad3, negatively regulated Runx2 transcriptional activity. Menin and
      Smad3 were co-immunoprecipitated, and combined menin and Smad3 overexpression
      antagonized, whereas menin and the dominant-negative Smad3DeltaC together
      enhanced BMP-2-induced transcriptional activity of Smad1/5 and Runx2. Smad3 alone
      had no effect. Therefore, menin interacts physically and functionally with Runx2
      in uncommitted mesenchymal stem cells, but not in well differentiated
      osteoblasts. In osteoblasts the interaction of menin and the transforming growth
      factor-beta/Smad3 pathway negatively regulates the BMP-2/Smad1/5- and Runx2
      induced transcriptional activities leading to inhibition of late-stage
      differentiation.

PMID- 15150274
TI  - Targeting of the dual oxidase 2 N-terminal region to the plasma membrane.
AB  - Dual oxidase 2 (Duox2) is a cell surface glycoprotein that probably provides
      thyroperoxidase with the H2O2 required to catalyze thyroid hormone synthesis. No
      functional H2O2-generating system has yet been obtained after transfecting Duox2
      into non-thyroid cell lines, because it is retained in the endoplasmic reticulum
      (ER). We investigated the level of maturation of various Duox2 truncated proteins
      in an attempt to identify the region of Duox2 responsible for its remaining in
      the ER. Duox2-Q686X mutant, corresponding to the N-terminal ectodomain including
      the first putative transmembrane domain, was expressed in different cell lines.
      Carbohydrate content analysis revealed that complex type-specific Golgi apparatus
      (GA) oligosaccharides were present on pig Duox2-Q686X, whereas human truncated
      Duox2 carried only high mannose-type sugar chains characteristic of the ER.
      Further characterization using surface biotinylation and flow cytometry assays
      indicated that pig Duox2-Q686X was present at the plasma membrane, whereas human
      Duox2-Q686X remained inside the cell. The replacement of the last 90 residues of
      the human Duox2-Q686X with the pig equivalent region allowed the chimerical
      peptide to reach the Golgi apparatus. Pig mutants containing the complete first
      intracellular loop with or without the second transmembrane domain accumulated in
      the ER. These findings show that 1) the human Duox2-Q686X region encompassing
      residues 596-685 prevents mutant exportation from the ER and 2) there is a pig
      Duox2 retention domain in the first intracellular loop. In addition, missense
      mutations of four cysteines (Cys-351, -370, -568, or -582) completely inhibited
      the emergence of pig Duox2-Q686X from the ER compartment, indicating their
      importance in Duox2 maturation.

PMID- 15150275
TI  - Protein splicing and auto-cleavage of bacterial intein-like domains lacking a C'
      flanking nucleophilic residue.
AB  - Bacterial intein-like (BIL) domains are newly identified homologs of intein
      protein-splicing domains. The two known types of BIL domains together with
      inteins and hedgehog (Hog) auto-processing domains form the Hog/intein (HINT)
      superfamily. BIL domains are distinct from inteins and Hogs in sequence,
      phylogenetic distribution, and host protein type, but little is known about their
      biochemical activity. Here we experimentally study the auto-processing activity
      of four BIL domains. An A-type BIL domain from Clostridium thermocellum showed
      both protein-splicing and auto-cleavage activities. The splicing is notable,
      because this domain has a native Ala C'-flanking residue rather than a
      nucleophilic residue, which is absolutely necessary for intein protein splicing.
      B-type BIL domains from Rhodobacter sphaeroides and Rhodobacter capsulatus
      cleaved their N' or C' ends. We propose an alternative protein-splicing mechanism
      for the A-type BIL domains. After an initial N-S acyl shift, creating a thioester
      bond at the N' end of the domain, the C' end of the domain is cleaved by Asn
      cyclization. The resulting amino end of the C'-flank attacks the thioester bond
      next at the N' end of the domain. This aminolysis step splices the two flanks of
      the domain. The B-type BIL domain cleavage activity is explained in the context
      of the canonical intein protein-splicing mechanism. Our results suggest that the
      different HINT domains have related biochemical activities of proteolytic
      cleavages, ligation and splicing. Yet the predominant reactions diverged in each
      HINT type according to their specific biological roles. We suggest that the BIL
      domain cleavage and splicing reactions are mechanisms for post-translationally
      generating protein variability, particularly in extracellular bacterial proteins.

PMID- 15150276
TI  - Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein
      coupled receptor proteolytic site motif.
AB  - Post-translational cleavage at the G protein-coupled receptor proteolytic site
      (GPS) has been demonstrated in many class B2 G protein-coupled receptors as well
      as other cell surface proteins such as polycystin-1. However, the mechanism of
      the GPS proteolysis has never been elucidated. Here we have characterized the
      cleavage of the human EMR2 receptor and identified the molecular mechanism of the
      proteolytic process at the GPS. Proteolysis at the highly conserved His-Leu
      downward arrow Ser(518) cleavage site can occur inside the endoplasmic reticulum
      compartment, resulting in two protein subunits that associate noncovalently as a
      heterodimer. Site-directed mutagenesis of the P(+1) cleavage site (Ser(518))
      shows an absolute requirement of a Ser, Thr, or Cys residue for efficient
      proteolysis. Substitution of the P(-2) His residue to other amino acids produces
      slow processing precursor proteins, which spontaneously hydrolyze in a defined
      cell-free system. Further biochemical characterization indicates that the GPS
      proteolysis is mediated by an autocatalytic intramolecular reaction similar to
      that employed by the N-terminal nucleophile hydrolases, which are known to
      activate themselves by self-catalyzed cis-proteolysis. We propose here that the
      autoproteolytic cleavage of EMR2 represents a paradigm for the other GPS motif
      containing proteins and suggest that these GPS proteins belong to a cell surface
      receptor subfamily of N-terminal nucleophile hydrolases.

PMID- 15150277
TI  - Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast
      cancer growth and metastasis.
AB  - Metastasis is a leading cause of mortality and morbidity in cancer. Urokinase
      (uPA), only expressed by the highly invasive cancer cells, has been implicated in
      invasion, metastases, and angiogenesis of several malignancies including breast
      cancer. Because uPA expression is strongly correlated with its hypomethylated
      state, we utilized the uPA gene in the highly invasive MDA-231 human breast
      cancer cells as a model system to test the hypothesis that pharmacological
      reversal of the uPA promoter hypomethylation would result in its silencing and
      inhibition of metastasis. S-Adenosyl-l-methionine (AdoMet) has previously been
      shown to cause hypermethylation and inhibit demethylation. Treatment of MDA-231
      cells with AdoMet, but not its unmethylated analogue S-adenosylhomocysteine,
      significantly inhibits uPA expression and tumor cell invasion in vitro and tumor
      growth and metastasis in vivo. The effects of AdoMet on uPA expression were
      reversed by the demethylating agent 5'-azacytidine, supporting the conclusion
      that AdoMet effects are caused by hypermethylation. Knockdown of the methyl
      binding protein 2 also causes a significant inhibition of uPA expression in vitro
      and tumor growth and metastasis in vivo. These treatments did not have any
      effects on estrogen receptor expression, suggesting that inhibition of
      hypomethylation will not affect genes already silenced by hypermethylation. These
      data are consistent with the hypothesis that hypomethylation of critical genes
      like uPA plays a causal role in metastasis. Inhibition of hypomethylation can
      thus be used as a novel therapeutic approach to silence the pro-metastatic gene
      uPA and block breast cancer progression into the aggressive and metastatic stages
      of the disease.

PMID- 15150278
TI  - Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast
      cells.
AB  - Nodal, a member of the transforming growth factor-beta superfamily, is known to
      play critical roles in early vertebrate development, but its functions in
      extraembryonic tissues are unclear. ALK7 is a type I receptor for Nodal.
      Recently, we demonstrated that Nodal mRNA and several ALK7 transcripts are
      expressed in human placenta throughout pregnancy (Roberts, H. J., Hu, S., Qiu,
      Q., Leung, P. C. K., Cannigia, I., Gruslin, A., Tsang, B., and Peng, C. (2003)
      Biol. Reprod. 68, 1719-1726). In this study, we determined the role of Nodal and
      ALK7 in trophoblast cell proliferation and apoptosis. Overexpression of Nodal in
      normal trophoblast cells (HTR8/SVneo) and several choriocarcinoma cell lines
      resulted in a significant decrease in the number of metabolically active cells.
      The effect of Nodal could be mimicked by constitutively active ALK7 (ALK7-ca),
      but was blocked by kinase-deficient ALK7. The growth inhibitory effect of Nodal
      was also blocked by dominant-negative Smad2/3. Overexpression of Nodal and ALK7
      ca induced apoptosis in trophoblast cells as determined by Hoechst staining, flow
      cytometry, and caspase-3 Western blotting. In addition, Nodal and ALK7-ca
      decreased the number of proliferating cells as measured by bromodeoxyuridine
      assays. Furthermore, overexpression of Nodal or ALK7-ca increased p27 expression,
      but reduced the levels of Cdk2 and cyclin D(1). Taken together, this study
      demonstrates for the first time that Nodal, acting through ALK7 and Smad2/3,
      inhibits proliferation and induces apoptosis in human trophoblast cells. Our
      findings also suggest that the Nodal-ALK7 pathway inhibits cell proliferation by
      inducing G(1) cell cycle arrest and that this effect is mediated in part by the
      p27-cyclin E/Cdk2 pathway.

PMID- 15150279
TI  - Design of novel and selective inhibitors of urokinase-type plasminogen activator
      with improved pharmacokinetic properties for use as antimetastatic agents.
AB  - The serine protease urokinase-type plasminogen activator (uPA) interacts with a
      specific receptor (uPAR) on the surface of various cell types, including tumor
      cells, and plays a crucial role in pericellular proteolysis. High levels of uPA
      and uPAR often correlate with poor prognosis of cancer patients. Therefore, the
      specific inhibition of uPA with small molecule active-site inhibitors is one
      strategy to decrease the invasive and metastatic activity of tumor cells. We have
      developed a series of highly potent and selective uPA inhibitors with a C
      terminal 4-amidinobenzylamide residue. Optimization was directed toward reducing
      the fast elimination from circulation that was observed with initial analogues.
      The x-ray structures of three inhibitor/uPA complexes have been solved and were
      used to improve the inhibition efficacy. One of the most potent and selective
      derivatives, benzylsulfonyl-D-Ser-Ser-4-amidinobenzylamide (inhibitor 26),
      inhibits uPA with a Ki of 20 nm. This inhibitor was used in a fibrosarcoma model
      in nude mice using lacZ-tagged human HT1080 cells, to prevent experimental lung
      metastasis formation. Compared with control (100%), an inhibitor dose of 2 x 1.5
      mg/kg/day reduced the number of experimental metastases to 4.6 +/- 1%. Under
      these conditions inhibitor 26 also significantly prolonged survival. All mice
      from the control group died within 43 days after tumor cell inoculation, whereas
      50% of mice from the inhibitor-treated group survived more than 117 days. This
      study demonstrates that the specific inhibition of uPA by these inhibitors may be
      a useful strategy for the treatment of cancer to prevent metastasis.

PMID- 15150280
TI  - Metabolic mapping of proteinase activity with emphasis on in situ zymography of
      gelatinases: review and protocols.
AB  - Proteases are essential for protein catabolism, regulation of a wide range of
      biological processes, and in the pathogenesis of many diseases. Several
      techniques are available to localize activity of proteases in tissue sections or
      cell preparations. For localization of the activity of matrix metalloproteinases,
      in situ zymography was introduced some decades ago. The procedure is based on
      zymography using SDS polyacrylamide gels containing gelatin, casein, or fibrin as
      substrate. For in situ zymography, either a photographic emulsion containing
      gelatin or a fluorescence-labeled proteinaceous macromolecular substrate is
      brought into contact with a tissue section or cell preparation. After incubation,
      enzymatic activity is revealed as white spots in a dark background or as black
      spots in a fluorescent background. However, this approach does not allow precise
      localization of proteinase activity because of limited sensitivity. A major
      improvement in sensitivity was achieved with the introduction of dye-quenched (DQ
      )gelatin, which is gelatin that is heavily labeled with FITC molecules so that
      its fluorescence is quenched. After cleavage of DQ-gelatin by gelatinolytic
      activity, fluorescent peptides are produced that are visible against a weakly
      fluorescent background. The incubation with DQ-gelatin can be combined with
      simultaneous immunohistochemical detection of a protein on the same section. To
      draw valid conclusions from the findings with in situ zymography, specific
      inhibitors need to be used and the technique has to be combined with
      immunohistochemistry and zymography. In that case, in situ zymography provides
      data that extend our understanding of the role of specific proteinases in various
      physiological and pathological conditions.

PMID- 15150281
TI  - Functional analysis of the matricellular protein SPARC with novel monoclonal
      antibodies.
AB  - SPARC (osteonectin, BM-40) is a matricellular glycoprotein that is expressed in
      many embryogenic and adult tissues undergoing remodeling or repair. SPARC
      modulates cellular interaction with the extracellular matrix (ECM), inhibits cell
      adhesion and proliferation, and regulates growth factor activity. To explore
      further the function and activity of this protein in tissue homeostasis, we have
      developed several monoclonal antibodies (MAbs) that recognize distinct epitopes
      on SPARC. The MAbs bind to SPARC with high affinity and identify SPARC by ELISA,
      Western blotting, immunoprecipitation, immunocytochemistry, and/or
      immunohistochemistry. The MAbs were also characterized in functional assays for
      potential alteration of SPARC activity. SPARC binds to collagen I and laminin-1
      through an epitope defined by MAb 293; this epitope is not involved in the
      binding of SPARC to collagen III. The other MAbs did not interfere with the
      binding of SPARC to collagen I or III or laminin-1. Inhibition of the anti
      adhesive effect of SPARC on endothelial cells by MAb 236 was also observed.
      Functional analysis of SPARC in the presence of these novel MAbs now confirms
      that the activities ascribed to this matricellular protein can be assigned to
      discrete subdomains.

PMID- 15150282
TI  - Expression and characterization of murine hevin (SC1), a member of the SPARC
      family of matricellular proteins.
AB  - Hevin, also known as SC1, MAST 9, SPARC-like 1, RAGS1 and ECM2, is a member of
      the SPARC-related family of matricellular proteins. Mouse hevin is 53% identical
      to mouse SPARC, and both proteins share a follistatin-like module and an
      extracellular Ca(2+)-binding (E-C) domain. SPARC functions as a modulator of cell
      matrix interactions, a regulator of growth factor activity, a de-adhesive
      protein, and a cell cycle inhibitor. Although the functions of mouse hevin are
      unknown, its human orthologue has been shown to be de-adhesive for endothelial
      cells. We now report the production of recombinant mouse hevin in insect cells
      through the use of a baculoviral expression system and its purification by anion
      exchange, size-exclusion chromatography, and isoelectric focusing. Furthermore,
      we have produced rat anti-hevin monoclonal antibodies (MAbs) that have been
      characterized by indirect and capture ELISAs, immunoblotting,
      immunoprecipitation, and immunohistochemistry (IHC). Recombinant hevin, present
      as a soluble factor or bound to tissue-culture plastic, inhibited the spreading
      of bovine aortic endothelial cells in vitro. IHC analysis of hevin in normal
      human and mouse tissues revealed a limited expression pattern in many tissues,
      with particularly dominant staining in dermis, ducts, vasculature, muscle, and
      brain. In lung and pancreatic tumor xenografts, we found distinct reactivity with
      MAbs that were selective for stromal cells, tumor cells, and/or endothelial
      cells. Although similar to SPARC in its anti-adhesive activities, hevin
      nevertheless exhibits a distinctive histological distribution that, in certain
      invasive tumors, is associated with desmoplasia.

PMID- 15150283
TI  - The influence of oxygen and tumor necrosis factor-alpha on the cellular kinetics
      of term placental villous explants in culture.
AB  - Explanted placental fragments may provide a more physiological in vitro model of
      component cell function than single cell isolates. We have characterized these
      fragments for cell turnover and have monitored responses from 14 normal placentas
      under conditions of exogenous TNFalpha and atypical oxygen concentrations (3% and
      17%), conditions associated with abnormal pregnancy and an aberrant in utero
      environment. Explants were assessed for apoptotic morphology, immunolocalization
      of Mib-1 (a proliferation marker), caspase 3 activity (an apoptosis promoter),
      lactate dehydrogenase (a necrosis marker), and human chorionic gonadotrophin
      [hCG, a marker of cytotrophoblast (CT) differentiation]. Consistent with a
      reduction in hCG, explants under 17% O(2) (with and without TNFalpha) showed a
      progressive degeneration of syncytiotrophoblast (ST) (days 0-2) followed by a
      restoration of hCG (days 4-8) localized to newly differentiated but not
      syncytialized CTs. In 3% O(2), hCG showed the same initial decline but failed to
      recover thereafter. Proliferation dropped significantly in 17% O(2) but was
      restored and exaggerated sixfold in 3% O(2). All reductions in hCG were
      associated with cell death and caspase-3. Early apoptosis was linked with
      syncytial loss; later apoptosis (days 8-11) was localized to the non-ST.
      Prolonged exposure to TNFalpha (days 4-11) increased ST apoptosis and necrosis
      but 3% O(2) had no significant effect. These findings show that placental
      explants can accommodate many aspects of CT proliferation, differentiation, and
      ST apoptosis in culture. TNFalpha enhanced ST decline but 3% oxygen (compared
      with 17%) was associated with reduced CT differentiation and a strong shift
      towards proliferation. These outcomes may reflect previous morphological changes
      in compromised pregnancies and confirm a possible role for oxygen and TNFalpha in
      aberrant trophoblast turnover.

PMID- 15150285
TI  - Immunohistochemical study of protein 4.1B in the normal and W/W(v) mouse
      seminiferous epithelium.
AB  - Cell-cell adhesion is crucial not only for mechanical adhesion but also for
      tissue morphogenesis. Protein 4.1B, a member of the protein 4.1 family named from
      an erythrocyte membrane protein, is a potential organizer of an adherens system.
      In adult mouse seminiferous tubules, protein 4.1B localized in the basal
      compartment, especially in the attaching region of spermatogonia and Sertoli
      cells. Protein 4.1B localization and appearance were not different in each
      spermatogenic stage. Developmentally, protein 4.1B was not detected at postnatal
      day 3 (P3), was diffusely localized at P15, and was found in the basal
      compartment during the third week. By double staining for protein 4.1B and F
      actin, their localizations were shown to be different, indicating that protein
      4.1B was localized in a region lower than the basal ectoplasmic specialization
      that formed the Sertoli-Sertoli junction. By electron microscopy, immunoreactive
      products were seen mainly on the membranes of Sertoli cells. In the W/W(v) mutant
      mouse, the seminiferous epithelium had few germ cells. Protein 4.1B and beta
      catenin were not detected, although the basal ectoplasmic specialization was
      retained. These results indicate that protein 4.1B may be related to the adhesion
      between Sertoli cells and germ cells, especially the spermatogonium.

PMID- 15150284
TI  - Alveolar epithelial type I cells express beta2-adrenergic receptors and G-protein
      receptor kinase 2.
AB  - Beta2-Adrenergic agonists stimulate alveolar epithelial sodium (Na(+)) transport
      and lung fluid clearance. Alveolar type II (AT2) cells have been reported to
      express beta2-adrenergic receptors (beta2AR). Given the large surface area
      covered by alveolar type I (AT1) cells and their potential role in alveolar fluid
      removal, we were interested in learning if AT1 cells express beta2AR as well.
      Because beta2AR is potentially susceptible to desensitization by G-protein
      coupled receptor kinase 2 (GRK2), we also undertook localization of GRK2. beta2AR
      and GRK2 expression was evaluated in whole lung, isolated alveolar epithelial
      cells (AECs), and AECs in primary culture, and was localized to specific AEC
      phenotypes by immunofluorescence techniques. beta2AR is highly expressed in AT1
      cells. beta2AR mRNA increases with time in culture as AT2 cells
      transdifferentiate towards the AT1 cell phenotype. Immunoreactive GRK2 is seen in
      both AT1 and AT2 cells in similar amounts. These data suggest that both AT1 and
      AT2 cells may contribute to the increased alveolar Na(+) and water clearance
      observed after exposure to beta2 adrenergic agents. Both cell types also express
      GRK2, suggesting that both may undergo desensitization of beta2AR with subsequent
      decline in the stimulatory effects of beta2-adrenergic agonists over time.

PMID- 15150287
TI  - Presence of collagen IV in the ciliary zonules of the human eye: an
      immunohistochemical study by LM and TEM.
AB  - The ciliary zonules of the eye are composed of fibrillar and non-fibrillar
      components. Fibrils provide tensile strength and elasticity, whereas non
      fibrillar components serve as a coating surrounding the fibrils. This coating
      behaves as a barrier to macromolecules. The present light and transmission
      electron microscopic (LM and TEM) study identified collagen IV as a novel
      component of this coating. Collagen IV was demonstrated by pre-embedding and
      postembedding immunohistochemical (IHC) techniques using monoclonal and
      polyclonal antibodies. The specificity of the polyclonal anticollagen IV antibody
      was verified by ELISA.

PMID- 15150286
TI  - The vesicular monoamine transporter 2 (VMAT2) is expressed by normal and tumor
      cutaneous mast cells and Langerhans cells of the skin but is absent from
      Langerhans cell histiocytosis.
AB  - Monoamine storage in secretory granules is mediated by the vesicular monoamine
      transporters 1 and 2 (VMAT1 and VMAT2). The aim of our study was to identify
      monoamine-handling normal and neoplastic inflammatory cells in the skin by their
      expression of VMAT1 and VMAT2. Normal skin from various parts of the body, as
      well as 21 cases of cutaneous mastocytosis and 10 cases of cutaneous Langerhans
      cell histiocytosis were analyzed by immunohistochemistry, radioactive in situ
      hybridization, and double-fluorescence confocal microscopy. VMAT2-positive cells
      in the subepidermal layer were identified as mast cells by their expression of
      tryptase. Neoplastic mast cells in all cases of cutaneous mastocytosis retained
      their VMAT2 positivity. The intraepidermal VMAT2-expressing cells were identified
      as Langerhans cells by their CD1a positivity. VMAT2 was absent from Langerhans
      cell histiocytosis. VMAT2 is an excellent marker for normal and neoplastic mast
      cells. The expression of VMAT2 demonstrates the capacity of mast cells for
      monoamine storage and handling. The presence of VMAT2 in epidermal Langerhans
      cells revealed a previously unrecognized monoamine-handling phenotype of these
      cells and indicates possible involvement of amine storage and release associated
      with antigen presentation. Absence of VMAT2 in neoplastic Langerhans cells
      indicates a loss of monoamine handling capacity of these cells during
      tumorigenesis.

PMID- 15150288
TI  - Immunohistochemical detection of islet-1 and neuronal nitric oxide synthase in
      the dorsal root ganglia (DRG) of sheep fetuses during gestation.
AB  - This study first investigated the ontogeny of Islet-1 and neuronal nitric oxide
      synthase (nNOS) expression and their co-localization in the DRG of sheep fetuses
      during gestation by immunohistochemistry (IHC). The results showed that Islet-1
      and nNOS were located in the nuclei and cytoplasm of DRG neurons, respectively.
      The relative percentages of Islet-1-immunopositive (Islet-1(+)) neurons
      accounting for the total DRG neurons were 90%, 79%, 66%, and 53% at days 60, 90,
      and 120 of gestation and postnatally, respectively. The percentage of nNOS
      immunopositive (nNOS(+)) neurons was 94% at day 60 and declined to approximately
      30% at day 90, with no obvious further change until the postnatal period. Dual
      IHC showed that approximately 69% Islet-1(+) neurons express nNOS at day 60 of
      gestation. This proportion declined to approximately 24% at day 90, after which
      there was no significant change until birth. We also observed that most Islet
      1(+) and nNOS(+) neurons belonged to small and medium-sized DRG neurons from day
      90 of gestation to the postnatal period. These results suggest that both Islet-1
      and nNOS are important for the differentiation and maintenance of some specific
      phenotypes of DRG neurons during late gestation of sheep fetuses, although the
      related mechanisms need to be further elucidated.

PMID- 15150289
TI  - Crossreaction with an anti-Bax antibody reveals novel multi-endocrine cellular
      antigen.
AB  - We found a novel protein that has crossreactivity with a polyclonal anti-Bax
      antibody (SCBAX antibody). The protein was localized exclusively in the endocrine
      cells of hypothalamus, pituitary gland, and pancreatic islets.
      Immunohistochemical (IHC) double labeling revealed that the cells showing
      crossreactivity with this antibody corresponded precisely to oxytocin neurons and
      ACTH, alpha-MSH, and glucagon cells in rat and gerbil. By immunoelectron
      microscopy, the protein was localized predominantly in and just around the
      secretory granules in the cytoplasm but not in the mitochondria. Double-labeling
      IHC with the anti-Bax SCBAX antibody and two anti-Bax monoclonal antibodies
      (MAbs) showed that cells stained with the anti-Bax SCBAX antibody were not
      stained with anti-Bax MAbs except for very few cells (probably apoptotic cells).
      Western blotting analysis revealed that the molecular mass of the protein was
      approximately 55 kD, which differs from that of Bax protein (21 kD). These
      findings indicate that the anti-Bax SCBAX antibody recognizes not only pro
      apoptotic Bax protein (a 21-kD mitochondrial protein) but also an unknown
      substance present in one endocrine cell group in each endocrine organ. Therefore,
      the protein is designated as multi-endocrine cellular antigen (MECA). MECA is
      probably a 55-kD protein secreted from the particular differentiated cell groups
      of endocrine tissues.

PMID- 15150290
TI  - Quantification of in situ hybridization signals in rat testes.
AB  - We performed basic research into quantifying in situ hybridization (ISH) signals
      in rat testis, a suitable organ for the quantification because germ cells undergo
      synchronized development and show stage-specific gene expression. In this model
      experiment, rRNA was selected as the hybridizable RNA in paraffin sections.
      Specimens fixed with Bouin's fixative and hybridized with digoxygenin-labeled
      probes could easily be analyzed quantitatively through "posterization" of the
      images. The amount of rRNA hybridized with the probe was greatest in early
      primary spermatocytes, followed by pachytene primary spermatocytes, then
      diplotene spermatocytes, and finally by secondary spermatocytes and spermatids.
      The amounts reached low levels in metaphase, anaphase, and telophase of meiotic
      division and early step 1 spermatids, and then slightly increased during
      spermiogenesis. ISH rRNA staining was a useful parameter for evaluation of the
      quantitative analysis of mRNA and the levels of hybridizable RNA in tissue
      sections.

PMID- 15150291
TI  - Tissue distribution of the death ligand TRAIL and its receptors.
AB  - Recombinant human (rh) TNF-related apoptosis-inducing ligand (TRAIL) harbors
      potential as an anticancer agent. RhTRAIL induces apoptosis via the TRAIL
      receptors TRAIL-R1 and TRAIL-R2 in tumors and is non-toxic to nonhuman primates.
      Because limited data are available about TRAIL receptor distribution, we
      performed an immunohistochemical (IHC) analysis of the expression of TRAIL-R1,
      TRAIL-R2, the anti-apoptotic TRAIL receptor TRAIL-R3, and TRAIL in normal human
      and chimpanzee tissues. In humans, hepatocytes stained positive for TRAIL and
      TRAIL receptors and bile duct epithelium for TRAIL, TRAIL-R1, and TRAIL-R3. In
      brains, neurons expressed TRAIL-R1, TRAIL-R2, TRAIL-R3 but no TRAIL. In kidneys,
      TRAIL-R3 was negative, tubuli contorti expressed TRAIL-R1, TRAIL-R2, and TRAIL,
      and cells in Henle's loop expressed only TRAIL-R2. Heart myocytes showed
      positivity for all proteins studied. In colon, TRAIL-R1, TRAIL-R2, and TRAIL were
      present. Germ and Leydig cells were positive for all proteins studied.
      Endothelium in liver, heart, kidney, and testis lacked TRAIL-R1 and TRAIL-R2. In
      alveolar septa and bronchial epithelium TRAIL-R2 was expressed, brain vascular
      endothelium expressed TRAIL-R2 and TRAIL-R3, and in heart vascular endothelium
      only TRAIL-R3 was present. Only a few differences were observed between human and
      chimpanzee liver, brain, and kidney. In contrast to human, chimpanzee bile duct
      epithelium lacked TRAIL, TRAIL-R1, and TRAIL-R3, lung and colon showed no TRAIL
      or its receptors, TRAIL-R3 was absent in germ and Leydig cells, and vascular
      endothelium showed only TRAIL-R2 expression in the brain. In conclusion,
      comparable expression of TRAIL and TRAIL receptors was observed in human and
      chimpanzee tissues. Lack of liver toxicity in chimpanzees after rhTRAIL
      administration despite TRAIL-R1 and TRAIL-R2 expression is reassuring for rhTRAIL
      application in humans.

PMID- 15150292
TI  - Electron microscopic cytochemistry of adenylyl cyclase activity in mouse
      spermatozoa.
AB  - We investigated adenylyl cyclase activity of mouse spermatozoa by electron
      microscopic cytochemistry. Subcellular localization of enzyme activity was
      determined in the presence and absence of bicarbonate ions. Results confirm the
      existence in sperm of a bicarbonate-regulated adenylyl cyclase, which suggests
      microdomain signaling.

PMID- 15150293
TI  - Improved immunohistochemical method for detecting hypoxia gradients in mouse
      tissues and tumors.
AB  - We describe an improved immunohistochemical procedure for detecting regions of
      hypoxia in normal organs and tumors in mice. The method employs a primary
      fluorescein-conjugated mouse monoclonal antibody directed against pimonidazole
      protein adducts that are created in hypoxic tissues and a secondary mouse anti
      fluorescein antibody that is conjugated to horseradish peroxidase. Using these
      reagents, we clearly visualized the regions of relative hypoxia in implanted
      tumors in mice as well as in normal organs such as liver and kidney.
      Significantly, the resulting tissue sections were remarkably free of the
      background staining that is characteristically observed when rodent antibodies
      are used to detect antigens in rodent tissues.

PMID- 15150294
TI  - HERe-2 stay: the continuing importance of translational research in breast
      cancer.

PMID- 15150295
TI  - Mature results of adjuvant colon cancer trials from the fluorouracil-only era.

PMID- 15150296
TI  - Tobacco settlement seen as opportunity lost to curb cigarette use.

PMID- 15150297
TI  - Stat bite: Age-adjusted lung cancer mortality rates, 1990-2000.

PMID- 15150298
TI  - Metabolomics takes its place as latest up-and-coming "omic" science.

PMID- 15150300
TI  - Studies shedding light on vitamin D and cancer.

PMID- 15150301
TI  - When 50 percent is not the same as a coin toss: study examines decisions made
      based on statistics.

PMID- 15150302
TI  - Rational combinations of trastuzumab with chemotherapeutic drugs used in the
      treatment of breast cancer.
AB  - BACKGROUND: Trastuzumab, a humanized anti-HER2 antibody, increases the clinical
      benefit of first-line chemotherapy in patients with metastatic breast cancers
      that overexpress HER2. We characterized interactions between trastuzumab and
      chemotherapeutic agents commonly used in the treatment of breast cancer. METHODS:
      Multiple drug effect/combination index isobologram analysis was used to study the
      efficacy of chemotherapeutic drug plus trastuzumab combinations tested against
      four HER2-overexpressing breast cancer cell lines (SK-BR-3, BT-474, MDA-MB-361,
      and MDA-MB-453). Combination index values were derived from parameters of the
      median effect plots, and statistical tests were used to determine whether the
      mean combination index values at multiple effect levels were statistically
      significantly different from a combination index value of 1.0. Values less than
      1.0 indicate synergistic interactions, values greater than 1.0 indicate
      antagonistic interactions, and values equal to 1.0 indicate additive
      interactions. RESULTS: At a wide range of clinically achievable drug
      concentrations, synergistic interactions were observed in all four breast cancer
      cell lines for trastuzumab plus carboplatin (mean combination index values ranged
      from 0.32 [P<.001] to 0.53 [P<.001]), 4-hydroxycyclophosphamide (mean combination
      index values ranged from 0.38 [P<.001] to 0.73 [P =.010]), docetaxel (mean
      combination index values ranged from 0.30 [P<.001] to 0.62 [P<.001]), and
      vinorelbine (mean combination index values ranged from 0.24 [P<.001] to 0.78
      [P<.034]). Additive interactions were observed in all four cell lines with
      trastuzumab plus doxorubicin, epirubicin, and paclitaxel. Interactions between
      trastuzumab and gemcitabine were synergistic at low concentrations of gemcitabine
      and antagonistic at high concentrations. A synergistic interaction was observed
      with a three-drug combination of docetaxel plus carboplatin plus trastuzumab in
      SK-BR-3 cells (mean combination index value = 0.09; P<.001). CONCLUSION:
      Consistent synergistic interactions of trastuzumab plus carboplatin, 4
      hydroxycyclophosphamide, docetaxel, or vinorelbine across a wide range of
      clinically relevant concentrations in HER2-overexpressing breast cancer cells
      indicate that these are rational combinations to test in human clinical trials.

PMID- 15150303
TI  - Randomized trial of intraportal and/or systemic adjuvant chemotherapy in patients
      with colon carcinoma.
AB  - BACKGROUND: 5-fluorouracil-based adjuvant chemotherapy after surgical resection
      of colon cancer is standard treatment. However, the choice of best delivery route
      -that is, systemic (i.e., intravenous or oral) or regional (i.e., intraportal,
      intraperitoneal, or hepatic arterial infusion)--has been controversial. In a
      randomized clinical trial of patients with colon cancer, we compared the benefits
      of chemotherapy delivered by these routes individually or in combination.
      METHODS: From April 2, 1992, through April 30, 1998, 1084 eligible patients with
      Dukes' stage B or C colon carcinoma were randomly assigned: 369 patients to the
      IP regimen (continuous portal vein infusion of 5-fluorouracil at 500 mg/m2 of
      body surface daily and heparin at 5000 IU daily for 7 consecutive days, beginning
      on the day of surgery), 358 patients to the SY regimen (six 28-day courses of
      systemic leucovorin at 100 mg/m2 daily on days 1 through 5 followed by systemic
      bolus 5-fluorouracil at 370 mg/m2 daily on days 1 through 5, with treatment
      initiated 15-35 days after surgery), and 357 patients to the IP+SY regimen (the
      IP regimen followed by the SY regimen, with the same scheduling). Primary
      survival was analyzed with the log-rank statistic and a Cox multivariable
      regression model. All statistical tests were two sided. RESULTS: At a median
      follow-up time of 99 months, 389 events (recurrences, second malignancies, or
      deaths) had occurred, and 361 patients died. Sites of first recurrences were
      similar among the three arms. At 5 years, overall and event-free survival rates
      were similar among those on the IP (74% and 68%, respectively), SY (78% and 71%),
      and IP+SY (73% and 67%) regimens. When compared with the group on the SY regimen,
      the risk for death associated with the IP regimen (hazard ratio [HR] = 1.05, 95%
      confidence interval [CI] = 0.82 to 1.36) was similar to that associated with the
      IP+SY regimen (HR = 1.12, 95% CI = 0.78 to 1.45) (P =.69), as were the risks for
      first event (HR = 1.07, 95% CI = 0.84 to 1.37 and HR = 1.10, 95% CI = 0.86 to
      1.41, respectively) (P=.74). CONCLUSION: Overall and event-free survival rates
      were similar in all three arms. The combined regimen was no better than either
      single regimen alone.

PMID- 15150304
TI  - Results of two open-label, multicenter phase II studies of docetaxel, platinum
      salts, and trastuzumab in HER2-positive advanced breast cancer.
AB  - BACKGROUND: Preclinical data indicate that docetaxel, platinum salts, and the
      combination of both drugs are highly synergistic with the anti-HER2 antibody
      trastuzumab. The University of California at Los Angeles-Oncology Research
      Network (UCLA-ORN) and the Breast Cancer International Research Group (BCIRG)
      have conducted two phase II studies to evaluate docetaxel and trastuzumab in
      combination with either cisplatin or carboplatin for the treatment of women with
      advanced breast cancer that overexpresses HER2. METHODS: Each study enrolled 62
      patients with HER2-overexpressing tumors. Patients received a median of six
      cycles of docetaxel at 75 mg/m2 of body surface area and cisplatin (BCIRG 101
      study) at 75 mg/m2 or carboplatin (UCLA-ORN study) at AUC = 6 mg/mL. min given on
      day 1 and then every 21 days. Trastuzumab was given on day 1, cycle 1 (4 mg/kg)
      and then continued weekly at 2 mg/kg for 1 year or until disease progression.
      Tumor measurements were obtained at baseline, after three cycles of chemotherapy,
      and then every 3 months. HER2 gene amplification was determined by fluorescence
      in situ hybridization. RESULTS: Patient characteristics were comparable between
      trials with the exception that 15% of the patients in the UCLA-ORN study had
      received previous adjuvant taxane therapy. Both regimens were well tolerated,
      with manageable toxicities. Hematologic toxicities were more frequent in patients
      in the UCLA-ORN study than in patients in the BCIRG 101 study, whereas the
      reverse pattern was observed for non-hematologic toxicities. One patient in each
      study developed reversible congestive heart failure. Responses were observed in
      49 of 62 patients in the BCIRG 101 study (overall response rate = 79%, 95%
      confidence interval [CI] = 66% to 89%) and in 34 of 59 evaluable patients in the
      UCLA-ORN study (overall response rate = 58%, 95% CI = 44% to 70%). Median times
      to progression were 9.9 months (95% CI = 8.3 to 13.1 months) and 12.7 months (95%
      CI = 8.6 to 15.5 months) for patients in the BCIRG 101 and UCLA-ORN studies,
      respectively. Overall response rates were higher and median time to progression
      was longer in the subset of patients whose tumors harbored HER2 gene
      amplification. CONCLUSION: Combinations of docetaxel, a platinum salt, and
      trastuzumab are feasible and active in patients with advanced breast cancers that
      overexpress HER2. The BCIRG is conducting ongoing randomized studies of the three
      drug combination in both the metastatic and adjuvant settings.

PMID- 15150305
TI  - A randomized trial of direct mailing of fecal occult blood tests to increase
      colorectal cancer screening.
AB  - BACKGROUND: Although colorectal cancer screening by using a fecal occult blood
      test (FOBT), flexible sigmoidoscopy, colonoscopy, or barium enema x-ray reduces
      the incidence of and death from colorectal cancer, the rate of colorectal cancer
      screening in the general population is low. We conducted a randomized trial
      consisting of direct mailing of FOBT kits to increase colorectal cancer screening
      among residents of Wright County, Minnesota, a community in which colorectal
      cancer screening was promoted. METHODS: At baseline, we mailed a questionnaire
      about colorectal cancer screening to a random sample of Wright County residents
      aged 50 years or older who were randomly selected from the Minnesota State
      Driver's License and Identification Card database (estimated N = 1451). The
      sample was randomly allocated into three equal subgroups: one group (control)
      received only the questionnaire, one group received FOBT kits by direct mail with
      reminders, and one group received FOBT kits by direct mail without reminders.
      Study participants were sent a follow-up questionnaire 1 year after baseline. We
      used the responses to the questionnaires to estimate the 1-year change in self
      reported screening rates in each group and the differences in the changes among
      the groups, along with the associated bootstrap 95% confidence intervals (CIs).
      RESULTS: At baseline, the estimated response rate was 86.5%, self-reported
      adherence to FOBT guidelines was 21.5%, and overall adherence to any colorectal
      cancer screening test guidelines was 55.8%. The 1-year rate changes in absolute
      percentage for self-reported adherence to FOBT use were 1.5% (95% CI = -2.9% to
      5.9%) for the control group, 16.9% (95% CI = 11.5% to 22.3%) for the direct-mail
      FOBT-with-no-reminders group, and 23.2% (95% CI = 17.2% to 29.3%) for the direct
      mail-FOBT-with-reminders group. The 1-year rate changes for self-reported
      adherence to any colorectal cancer screening test were 7.8% (95% CI = 3.2% to
      12.0%) for the control group, 13.2% (95% CI = 8.4% to 18.2%) for the direct-mail
      FOBT-with-no-reminders group, and 14.1% (95% CI = 9.1% to 19.1%) for the direct
      mail-FOBT-with-reminders group. CONCLUSION: Direct mailing of FOBT kits combined
      with follow-up reminders promotes more rapid increases in the use of FOBT and
      nearly doubles the increase in overall rate of adherence to colorectal cancer
      screening guidelines in a general population compared with a community-wide
      screening promotion and awareness campaign.

PMID- 15150306
TI  - Familial clustering of Hodgkin lymphoma and multiple sclerosis.
AB  - BACKGROUND: Epidemiologic similarities between Hodgkin lymphoma in young adults
      (i.e., between 15 and 44 years old) and multiple sclerosis have led to the
      suggestion that these diseases may have related etiologies. Previous
      investigations have not supported this hypothesis, but the negative results could
      have been caused by methodologic problems. We therefore assessed the risk of
      developing Hodgkin lymphoma for patients with multiple sclerosis and for their
      families and the risk of developing multiple sclerosis for patients with Hodgkin
      lymphoma and for their families. METHODS: We identified 11,790 patients with
      multiple sclerosis and 19,599 of their first-degree relatives in Danish
      population-based registers and followed them for the occurrence of Hodgkin
      lymphoma. Analogously, we identified 4381 patients with Hodgkin lymphoma and 7388
      of their first-degree relatives and followed them for the occurrence of multiple
      sclerosis. The relative risks (RRs) of Hodgkin lymphoma and multiple sclerosis
      were expressed as standardized incidence ratios (i.e., the ratio between observed
      and expected numbers of outcomes based on age, sex, and period-specific incidence
      rates). All statistical tests were two-sided. RESULTS: Overall, six cases of
      Hodgkin lymphoma were identified in patients with multiple sclerosis (RR for
      Hodgkin lymphoma = 1.40, 95% confidence interval [CI] = 0.63 to 3.12), two of
      which occurred in young adults (RR = 1.59, 95% CI = 0.40 to 6.37). The risk of
      young-adult-onset Hodgkin lymphoma was statistically significantly increased in
      the first-degree relatives of patients with multiple sclerosis (RR = 1.93, 95% CI
      = 1.01 to 3.71; n = 9 such lymphomas). Two cases of multiple sclerosis were
      identified among young adult patients with Hodgkin lymphoma (RR for multiple
      sclerosis = 0.82, 95% CI = 0.20 to 3.27), and the risk for multiple sclerosis was
      statistically significantly increased in their first-degree relatives (RR = 2.76,
      95% CI = 1.44 to 5.31; n = 9 such multiple sclerosis cases). CONCLUSION: The
      observed familial clustering of multiple sclerosis and young-adult-onset Hodgkin
      lymphoma is consistent with the hypothesis that the two conditions share
      environmental and/or constitutional etiologies.

PMID- 15150307
TI  - Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample
      unselected by family history and in melanoma-prone families.
AB  - BACKGROUND: Few family studies have investigated the effects of genetic,
      environmental, and host factors on melanoma risk, and most have been restricted
      to high-risk families. We assessed the role of these factors on melanoma risk in
      two types of families: families ascertained through melanoma probands but
      unselected by family history and melanoma-prone families. METHODS: Data on
      pigmentary traits, nevus phenotypes, exposure to sun, and reactions to sunlight
      were collected from 295 families unselected by family history and 53 melanoma
      prone families. We modeled melanoma risk using a logistic regressive model
      incorporating the effect of a melanoma-predisposing gene, familial dependence,
      and potential risk factors (e.g., pigmentary traits, nevus phenotypes, history of
      sun exposure, skin reactions to sunlight). Maximum-likelihood estimates of the
      parameters of the regressive model were used to compute odds ratios associated
      with each risk factor and age-specific melanoma risk depending on the genotype at
      the melanoma-predisposing gene and the effects of risk factors. All statistical
      tests were two-sided. RESULTS: In the families unselected by family history,
      there was statistically significant evidence (P<.001) for a dominant gene, with
      melanoma risk reaching 0.49 and 0.67 by age 80 years in male and female gene
      carriers, respectively. Melanoma risk was statistically significantly influenced
      by total nevi (odds ratio of hazard function [OR] = 5.81, 95% confidence interval
      [CI] = 3.47 to 8.99), sun exposure (OR = 5.37, 95% CI = 4.44 to 6.36), and
      sunburn interacting with the gene (OR = 26.31, 95% CI = 7.56 to 99.22 in gene
      carriers and OR = 1.67, 95% CI = 1.36 to 2.03 in noncarriers). Twenty of the 53
      melanoma-prone families had cosegregating mutations in CDKN2A, a gene known to be
      associated with melanoma. In these 53 families, three risk factors in addition to
      CDKN2A mutations increased melanoma risk: dysplastic nevi (OR = 2.32, 95% CI =
      2.08 to 2.58), total nevi (OR = 1.99, 95% CI = 1.61 to 2.20) and sunburn (OR =
      5.16, 95% CI = 4.82 to 5.52). CONCLUSIONS: Together, a melanoma-predisposing gene
      (identified as being CDKN2A in melanoma-prone families), number of nevi and/or
      dysplastic nevi, and sun-related covariates influence melanoma risk in both
      families unselected by family history and melanoma-prone families.

PMID- 15150308
TI  - Dose-dependent effects of dietary alpha- and gamma-tocopherols on genetic
      instability in mouse Mutatect tumors.
AB  - Vitamin E in foodstuffs is a mixture of tocopherols. In mouse Mutatect tumors, a
      model designed to detect DNA mutations, the hypoxanthine
      phosphoribosyltransferase (Hprt) gene mutation frequency is associated with the
      number of tumor-infiltrating neutrophils and both are markedly decreased in mice
      fed high levels of alpha-tocopherol. Dietary alpha-tocopherol is also associated
      with a decrease in neutrophil-associated loss of an interleukin 8 (IL-8)
      expressing transgene in this tumor model. We examined Hprt gene mutation
      frequency (expressed as the number of 6-thioguanine-resistant colonies per 10(5)
      clonable tumor cells), IL-8 transgene loss, and myeloperoxidase activity (an
      indirect measure of neutrophil number) in tumors from Mutatect mice fed diets
      supplemented with various concentrations of D-alpha-tocopherol acetate and/or D
      gamma-tocopherol acetate or neither tocopherol for 4 weeks. Hprt gene mutation
      frequency and myeloperoxidase activity were statistically significantly lower in
      tumor cells from mice fed alpha-tocopherol at 50 or 100 mg/kg body weight per day
      than in tumor cells from mice fed 0 mg/kg body weight per day alpha-tocopherol
      (P<.001 for each comparison). IL-8 transgene loss occurred in 28 of 28 tumors
      (100%; 95% confidence interval [CI] = 86% to 100%) from mice fed alpha-tocopherol
      at 50 mg or less/kg body weight per day and seven of 18 tumors (39%; 95% CI = 24%
      to 54%) from mice fed 100 mg/kg body weight per day (P<.001, Fisher's exact test,
      referent groups [pooled] 0, 25, and 50 mg/kg). gamma-Tocopherol had no detectable
      effect on any of the three endpoints. Thus, dietary alpha-tocopherol decreases
      two forms of genetic instability in a dose-dependent manner in this experimental
      tumor model.

PMID- 15150309
TI  - PET-CT modification of RECIST guidelines.

PMID- 15150310
TI  - Extended follow-up of cancer incidence in fluoride-exposed workers.

PMID- 15150312
TI  - Re: Lack of serologic evidence for prevalent simian virus 40 infection in humans.

PMID- 15150314
TI  - Re:Research and public health implications of the intricate relationship between
      calcium and vitamin D in the prevention of colorectal neoplasia.

PMID- 15150316
TI  - Expression and induction of cytochromes p450 in rat white adipose tissue.
AB  - Lipophilic environmental pollutants are often stored in adipose tissues after
      exposure. These compounds have been well studied in terms of their cell toxicity
      in organs such as liver and kidney, and their xenoestrogenic action on
      reproductive tissues as endocrine disruptors. However, the effects of these
      chemicals on the depot, adipose tissue, have not been studied, although adipose
      tissue is an important endocrine tissue secreting obesity/diabetes-related
      hormones and cytokines. In this study, we identified the expression of
      cytochromes P450 in rat white adipose tissues and investigated the effects of
      typical lipophilic cytochrome P450 inducers, namely phenobarbital, dexamethasone,
      and beta-naphthoflavone. The results showed that beta-naphthoflavone was a strong
      CYP1A inducer in adipose tissue as well as in liver. It increased CYP1A1 mRNA,
      protein, and its related activity, ethoxyresorufin O-deethylase. Phenobarbital
      and dexamethasone also induced both the mRNA and protein of CYP2Bs and CYP3As,
      respectively, in adipose tissue, although significant interindividual differences
      were observed. Furthermore, we demonstrated that 48 h of fasting was as effective
      in adipose tissue as in the liver in the induction of CYP2E1 mRNA and protein.
      These results suggest that the mechanisms by which cytochrome P450 genes are
      regulated in the liver are also functional in rat adipose tissues. This has
      raised the possibility that lipophilic environmental contaminants accumulated in
      adipose tissue may dysregulate the gene expression profile.

PMID- 15150317
TI  - Two classic cadherin-related molecules with no cadherin extracellular repeats in
      the cephalochordate amphioxus: distinct adhesive specificities and possible
      involvement in the development of multicell-layered structures.
AB  - We previously reported the existence of Bb-cadherin, a molecule related to
      classic cadherin, in the cephalochordate amphioxus (Branchiostoma belcheri). The
      structure of Bb-cadherin is unique in that it lacks the cadherin extracellular
      repeats, although its cytoplasmic domain shows close similarities to those of
      typical classic cadherins. The extracellular region of Bb-cadherin consists of
      laminin globular domains and a cysteine-rich EGF-like domain that are similar to
      domains in nonchordate classic cadherins. In this study, we identified a second
      amphioxus cadherin. It was designated Bb2-cadherin (Bb2C) while the previously
      reported cadherin has been renamed Bb1-cadherin (Bb1C). Bb2C is very similar to
      Bb1C in its overall structure and amino acid sequence. Genomic BLAST searches and
      phylogenetic analyses suggested that these two amphioxus genes have been
      generated through a gene duplication that occurred after separation of the
      cephalochordates from the other animals. They also bear distinct adhesive
      specificities. Immunohistochemical analyses showed that Bb1C and Bb2C, together
      with beta-catenin, appear to function as adherens junction constituents in the
      epithelia of different germ layers of the amphioxus embryo. Differential
      expression of the two cadherins was also observed in the developing, multicell
      layered notochord. These observations suggest that, despite their unique
      structures, the functions and developmental roles of Bb1C and Bb2C are comparable
      to those of the classic cadherins characterized to date in other animal groups,
      such as the vertebrate E- and N-cadherins and the Drosophila DE- and DN
      cadherins. The possible involvement of Bb1C and Bb2C in the development of
      multicell-layered structures characteristic of the cephalochordate body plan is
      presented.

PMID- 15150318
TI  - Anti-angiogenic action of the C-terminal domain of tenomodulin that shares
      homology with chondromodulin-I.
AB  - Tenomodulin (TeM) is a type II transmembrane glycoprotein that contains a C
      terminal domain with homology to the mature, secreted form of chondromodulin-I
      (ChM-I), a cartilage-derived angiogenesis inhibitor. TeM transcripts have been
      found in hypovascular tissues such as tendons and ligaments but the biological
      activity of TeM has not yet been fully explored. Using an adenovirus expression
      system, we utilized the forced expression and subsequent secretion of the human
      TeM C-terminal 116 amino acids (Ad-shTeM) in human umbilical vein endothelial
      cells (HUVECs) to assess the anti-angiogenic properties of TeM. The C-terminal
      120 amino acids of the human ChM-I precursor (Ad-shChM-I) was similarly expressed
      in HUVECs as a comparison study. Transduction of both Ad-shTeM and Ad-shChM-I
      resulted in significant impairment of the tube-forming activity of HUVECs, when
      cultured in Matrigel. Similarly, conditioned medium from COS7 cells, transfected
      with plasmid DNA encoding shTeM or shChM-I, inhibited tube formation of HUVECs
      when compared to medium derived from either COS7 cells transfected with control
      vector or from non-transfected cells. Upon infection of HUVECs with Ad-shTeM or
      Ad-shChM-I, DNA synthesis stimulated by vascular endothelial growth factor (VEGF)
      was reduced to 40-50% of normal levels. Additionally, in a modified Boyden
      chamber assay, migration of HUVECs in response to VEGF was significantly affected
      following transduction of either Ad-shTeM or Ad-shChM-I and these transduced
      HUVECs were found to spread well on type I collagen or fibronectin, but not on
      vitronectin. Furthermore, the transduction of either Ad-shTeM or Ad-shChM-I in
      human melanoma cells resulted in suppression of tumor growth in association with
      decreased vessel density in vivo. Hence, we have demonstrated that, similarly to
      ChM-1, the C-terminal domain of TeM exhibits both anti-angiogenic and anti-tumor
      activities when expressed in a secreted form.

PMID- 15150319
TI  - Dynamic changes in traction forces with DC electric field in osteoblast-like
      cells.
AB  - Primary bovine osteoblasts and human osteosarcoma cells exposed to direct-current
      electric fields undergo processes of retraction and elongation ultimately
      resulting in the realignment of the long cellular axis perpendicular to the
      electric field. The time taken for this reorientation was inversely correlated to
      field strength within a certain range. Cellular force output during reorientation
      was analyzed using a simple modification of traction force microscopy. The first
      detectable reaction was an increase in average traction force magnitude occurring
      between 10 and 30 seconds of electric field exposure. In the following 2 to 15
      minutes traction forces at margins tangential to the electric field decreased
      below their initial values. Phase-contrast microscopy revealed elongating
      protrusions at these margins several minutes later. We could not correlate the
      initial traction changes with any change in intracellular free calcium levels
      measured using the fluorescent dye Fura-2 AM.

PMID- 15150320
TI  - Role of the cytoskeleton in signaling networks.
AB  - Intracellular signal transduction occurs through cascades of reactions involving
      dozens of proteins that transmit signals from the cell surface, through a crowded
      cellular environment filled with organelles and a filamentous cytoskeleton, to
      specific targets. Numerous signaling molecules are immobilized or transiently
      bound to the cytoskeleton, yet most models for signaling pathways have no
      specific role for this mesh, which is often presumed to function primarily as a
      scaffold that determines cell mechanics but not information flow. We combined
      analytical tools with several recently established large-scale protein-protein
      interaction maps for Saccharomyces cerevisiae to quantitatively address the role
      of the cytoskeleton in intracellular signaling. The results demonstrate that the
      network of signaling proteins is intimately linked to the cytoskeleton,
      suggesting that this interconnected filamentous structure plays a crucial and
      distinct functional role in signal transduction.

PMID- 15150321
TI  - Axonal mitochondrial transport and potential are correlated.
AB  - Disruption of axonal transport leads to a disorganized distribution of
      mitochondria and other organelles and is thought to be responsible for some types
      of neuronal disease. The reason for bidirectional transport of mitochondria is
      unknown. We have developed and applied a set of statistical methods and found
      that axonal mitochondria are uniformly distributed. Analysis of fast axonal
      transport showed that the uniform distribution arose from the clustering of the
      stopping events of fast axonal transport in the middle of the gaps between
      stationary mitochondria. To test whether transport was correlated with ATP
      production, we added metabolic inhibitors locally by micropipette. Whereas
      applying CCCP (a mitochondrial uncoupler) blocked mitochondrial transport, as has
      been previously reported, treatment with antimycin (an inhibitor of electron
      transport at complex III) caused increases in retrograde mitochondrial transport.
      Application of 2-deoxyglucose did not decrease transport compared with the
      mannitol control. To determine whether mitochondrial transport was correlated
      with mitochondrial potential, we stained the neurons with the mitochondrial
      potential-sensing dye JC-1. We found that approximately 90% of mitochondria with
      high potential were transported towards the growth cone and approximately 80% of
      mitochondria with low potential were transported towards the cell body. These
      experiments show for the first time that a uniform mitochondrial distribution is
      generated by local regulation of the stopping events of fast mitochondrial
      transport, and that the direction of mitochondrial transport is correlated with
      mitochondrial potential. These results have implications for axonal clogging,
      autophagy, apoptosis and Alzheimer's disease.

PMID- 15150322
TI  - Involvement of the VEGF receptor 3 in tubular morphogenesis demonstrated with a
      human anti-human VEGFR-3 monoclonal antibody that antagonizes receptor activation
      by VEGF-C.
AB  - In this report we utilize a novel antagonist antibody to the human VEGFR-3 to
      elucidate the role of this receptor in in vitro tubular morphogenesis of bovine
      and human endothelial cells (EC cells) induced by VEGF-C. The antibody hF4-3C5
      was obtained by panning a human phage display library on soluble human VEGFR-3.
      The binding affinity constant of hF4-3C5 significantly exceeds that of the
      interaction of VEGFR-3 with VEGF-C. hF4-3C5 strongly inhibits the binding of
      soluble VEGFR-3 to immobilized VEGF-C and abolishes the VEGF-C-mediated mitogenic
      response of cells that expresses a chimeric human VEGFR-3-cFMS receptor. In
      fluorescence experiments, hF4-3C5 reactivity is observed with human lymphatic
      endothelial cells (LECs) and human umbilical vein endothelial cells (HUVECs).
      Binding of hF4-3C5 shows that about half of bovine aortic endothelial (BAE) cells
      express VEGFR-3 and cells in this subpopulation are primarily responsible for the
      chemotactic response to the mature form of VEGF-C (VEGF-C(DeltaNDeltaC)). This
      response was strongly inhibited by the addition of hF4-3C5. In vitro tube
      formation by BAE cells induced by VEGF-C(DeltaNDeltaC) was reduced by greater
      than 60% by hF4-3C5 whereas the response to VEGF(165) was unaffected. Addition of
      hF4-3C5 together with an antagonist antibody to VEGFR-2 completely abolished the
      response to VEGF-C(DeltaNDeltaC). Similar results were obtained with HUVECs.
      Together, these findings point to a role for VEGFR-3 in vascular tubular
      morphogenesis and highlight the utility of hF4-3C5 as a tool for the
      investigation of the biology of VEGFR-3.

PMID- 15150324
TI  - Advances in the biology, diagnosis and host-pathogen interactions of parvovirus
      B19.
AB  - Increased recognition of parvovirus B19 (B19), an erythrovirus, as a significant
      human pathogen that causes fetal loss and severe disease in immunocompromised
      patients has resulted in intensive efforts to understand the pathogenesis of B19
      related disease, to improve diagnostic strategy that is deployed to detect B19
      infection and blood-product contamination and, finally, to elucidate the nature
      of the cellular immune response that is elicited by the virus in diverse patient
      cohorts. It is becoming clear that at least three related erythrovirus strains
      (B19, A6/K71 and V9) are circulating in the general population and that viral
      entry into target cells is mediated by an expanding range of cellular receptors,
      including P antigen and beta-integrins. Persistent infection by B19 is emerging
      as a contributory factor in autoimmune disease, a hypothesis that is constrained
      by the detection of B19 in the skin of apparently healthy individuals. B19
      infection during pregnancy may account for thousands of incidences of fetal loss
      per annum in Europe, North America and beyond, yet there is currently only
      minimal screening of pregnant women to assess serological status, and thereby
      risk of infection, upon becoming pregnant. Whilst major advances in diagnosis of
      B19 infection have taken place, including standardization of serological and DNA
      based detection methodologies, blood donations that are targeted at high-risk
      groups are only beginning to be screened for B19 IgG and DNA as a means of
      minimizing exposure of at-risk patients to the virus. It is now firmly
      established that a Th1-mediated cellular immune response is mounted in
      immunocompetent individuals, a finding that should contribute to the development
      of an effective vaccine to prevent B19 infection in selected high-risk groups,
      including sickle-cell anaemics.

PMID- 15150325
TI  - Aerolysin is activated by metalloprotease in Aeromonas veronii biovar sobria.
AB  - Aeromonas veronii is an opportunistic human pathogen that causes diarrhoea and
      extraintestinal infections, such as wound infection and septicaemia. An A.
      veronii protease (AVP) from a biovar sobria strain, AeG1, was partially purified
      and characterized. Mature AVP hydrolysed casein but not elastin, and protease
      activity was inhibited by metalloprotease inhibitors. Nucleotide sequence
      analysis showed that AVP belongs to the thermolysin family of proteases. An AVP
      deficient mutant was constructed to investigate the role of AVP in aerolysin
      activation. Western blot analysis using anti-aerolysin antisera revealed that
      proaerolysin (52 kDa) in the AVP-deficient mutant was not completely activated to
      mature aerolysin (47 kDa) as seen in the wild-type strain. The AVP-deficient
      mutant showed lower cytotoxic and haemolytic activities than wild type. AVP and
      proaerolysin had no haemolytic activity; however, activity appeared after
      incubating both proteins. Taken together, these results suggested that AVP plays
      an indirect role in virulence through activating aerolysin, which is an essential
      step for cytotoxic activity.

PMID- 15150323
TI  - Genome coverage and sequence fidelity of phi29 polymerase-based multiple strand
      displacement whole genome amplification.
AB  - Major efforts are underway to systematically define the somatic and germline
      genetic variations causally associated with disease. Genome-wide genetic analysis
      of actual clinical samples is, however, limited by the paucity of genomic DNA
      available. Here we have tested the fidelity and genome representation of phi29
      polymerase-based genome amplification (phi29MDA) using direct sequencing and high
      density oligonucleotide arrays probing >10,000 SNP alleles. Genome representation
      was comprehensive and estimated to be 99.82% complete, although six regions
      encompassing a maximum of 5.62 Mb failed to amplify. There was no degradation in
      the accuracy of SNP genotyping and, in direct sequencing experiments sampling
      500,000 bp, the estimated error rate (9.5 x 10(-6)) was the same as in paired
      unamplified samples. The detection of cancer-associated loss of heterozygosity
      and copy number changes, including homozygous deletion and gene amplification,
      were similarly robust. These results suggest that phi29MDA yields high fidelity,
      near-complete genome representation suitable for high resolution genetic
      analysis.

PMID- 15150326
TI  - Characterization of a haemolytic phospholipase A(2) activity in clinical isolates
      of Campylobacter concisus.
AB  - A membrane-bound, haemolytic phospholipase A(2) (PLA(2)) activity was detected in
      clinical strains of Campylobacter concisus isolated from children with
      gastroenteritis. The clinical strains were assigned into two molecular groups
      (genomospecies) based on PCR amplification of their 23S rDNA. This calcium
      dependent, heat-stable, haemolytic PLA(2) activity was detected in strains from
      both genomospecies. A crude haemolysin extract (CHE) was initially prepared from
      cellular outer-membrane proteins of these isolates and was further fractionated
      by ultrafiltration. The haemolytic activity of the extracted fraction (R30) was
      retained by ultrafiltration using a 30 kDa molecular mass cut-off filter, and was
      designated haemolysin extract (HE). Both CHE and HE had PLA(2) activity and
      caused stable vacuolating and cytolytic effects on Chinese hamster ovary cells in
      tissue culture. Primers for the conserved region of pldA gene (phospholipase A
      gene) from Campylobacter coli amplified a gene region of 460 bp in all tested
      isolates, confirming the presence of a homologous PLA gene sequence in C.
      concisus. The detection of haemolytic PLA(2) activity in C. concisus indicates
      the presence of a potential virulence factor in this species and supports the
      hypothesis that C. concisus is a possible opportunistic pathogen.

PMID- 15150327
TI  - Effect of orally administered bovine lactoferrin on the immune response in the
      oral candidiasis murine model.
AB  - Therapeutic activity against oral candidiasis of orally administered bovine
      lactoferrin (LF), a multifunctional milk protein, was shown in a previous report
      using an immunosuppressed murine model. In the present study, the influence of
      orally administered LF on immune responses relevant to this therapeutic effect
      was examined. Because mice were immunosuppressed with prednisolone 1 day before
      and 3 days after the infection with Candida, the numbers of peripheral blood
      leukocytes (PBL) and cervical lymph node (CLN) cells were reduced. LF feeding
      prevented the reduction in the numbers of PBL on day 1 and CLN cells on days 1, 5
      and 6 in the Candida-infected mice. The number of CLN cells of individual mice on
      days 5 and 6 was inversely correlated with the Candida c.f.u. in the oral cavity.
      Increased production of IFN-gamma and TNF-alpha by CLN cells stimulated with heat
      killed Candida albicans on day 6 was observed in LF-treated mice compared with
      non-treated mice. Concanavalin A (ConA)-stimulated CLN cells from LF-treated mice
      also showed a significant increase in the production of IFN-gamma and IL12 on day
      5 and a tendency for increased production of IFN-gamma and TNF-alpha on day 6.
      The levels of cytokine production by ConA-stimulated CLN cells on day 6 were
      inversely correlated with the Candida c.f.u. in the oral cavity. In conclusion,
      the alleviation of oral candidiasis by LF feeding in this model may correlate
      with the enhancement of the number of leukocytes and their cytokine responses in
      regional lymph nodes against Candida infection.

PMID- 15150328
TI  - Transfer of specific antibodies results in increased expression of TNF-alpha and
      IL12 and recruitment of neutrophils to the site of a cutaneous Francisella
      tularensis infection.
AB  - This study demonstrates that passive transfer of Francisella tularensis-specific
      antibodies before experimental cutaneous infection with the live vaccine strain
      of F. tularensis has profound effects. Recipient mice showed stronger staining
      for TNF-alpha and IL12, and larger numbers of neutrophils in skin samples after
      infection than control mice.

PMID- 15150330
TI  - ELISA for early diagnosis of histoplasmosis.
AB  - An ELISA was developed and evaluated as a method for detecting antibodies against
      glycosylated and deglycosylated histoplasmin (HMIN). Sera from patients with
      histoplasmosis, paracoccidioidomycosis, sporotrichosis, coccidioidomycosis,
      aspergillosis, cryptococcosis and healthy donors were tested by ELISA against
      purified, deglycosylated histoplasmin (ptHMIN) and compared with purified, native
      (i.e. glycosylated) histoplasmin (pHMIN). Although cross-reactivity was not
      abolished when ptHMIN was used in the test, it was reduced (pHMIN ELISA 93 %
      versus ptHMIN ELISA 96 %). However, there were statistically significant
      differences between the sensitivities of these two methods for the detection of
      antibodies (pHMIN ELISA 57 % versus ptHMIN ELISA 92 %; P < 0.001) and between the
      efficiency of the methods (pHMIN ELISA 83 % versus ptHMIN ELISA 95 %; P < 0.001).
      These parameters compare better than previously published data relating to the
      use of treated HMIN in diagnostic ELISAs. Some of the reactivities of serum
      samples were compared by immunoblotting using deglycosylated HMIN and by
      immunodiffusion using the crude antigen. The results demonstrated that cross
      reactions with heterologous sera in both ELISAs could also be observed in
      immunoblotting and arose from shared protein epitopes. These data suggest that
      ELISA using deglycosylated HMIN is a very sensitive diagnostic method and, by
      using commercially available antigen, it can be easily standardized and performed
      faster than previous Western blot-based tests using the same antigen. It provides
      a useful adjunct to existing methods of diagnosis that could be applied even in
      situations where laboratory facilities were relatively limited.

PMID- 15150329
TI  - Equivalence of high-virulence clonotypes of serotype III group B Streptococcus
      agalactiae (GBS).
AB  - Analysis of growth characteristics, multilocus enzyme electrophoresis,
      restriction digest pattern (RDP) typing and multilocus sequence typing have
      identified clonotypes of serotype III group B Streptococcus agalactiae (GBS)
      associated with invasive infection in neonates. This study sought to unify
      phenotypic and genotypic classifications of type III GBS strains associated with
      increased virulence in newborns. High-virulence clonotype (HVC) strains possessed
      the translation initiation factor 2 (infB) C allele, found in RDP type III-3
      strains, and hybridized with the RDP type III-3-specific probe AA3.6, whereas non
      HVC strains shared the infB A allele and genomic DNA from these strains did not
      hybridize with the AA3.6 probe. The characteristic growth lag of HVC GBS at 40
      degrees C has been attributed to the presence of a heat-labile fructose-1,6
      bisphosphate aldolase (Fba) enzyme in these strains. The deduced amino acid
      sequence of fba genes of both HVC and non-HVC strains, however, were identical.
      HVC and RDP type III-3 represent the same genetically related group of bacteria.
      The characteristic growth differences of virulent strains of type III GBS,
      however, are not directly attributable to differences in fba.

PMID- 15150332
TI  - Laboratory diagnosis of pertussis infections: the role of PCR and serology.
AB  - This study reports on practical laboratory aspects of pertussis diagnosis. PCR
      assays were applied to respiratory specimens obtained during a large study of
      infants (less than 5 months old) admitted to paediatric intensive care units (n =
      122), children (less than 15 years old) admitted to paediatric wards (n = 16) and
      their household contacts (n = 320). Estimation of antibodies to pertussis toxin
      and culture for Bordetella pertussis were attempted on specimens from the same
      patients, where available, and the overall utility of the diagnostic PCR assays
      was assessed by comparison to these results. A PCR assay for the human
      mitochondrial cytochrome oxidase (HMCO) gene was used for quality control of the
      extracted samples and an internal process control (IPC) was included in each
      sample to test for PCR inhibition. Four of 458 samples were considered unsuitable
      (three HMCO negative, one IPC negative) and excluded from further analyses.
      Positive PCR results were considered valid if they were either (i) positive for
      both of two B. pertussis gene targets (pertussis toxin S1 promoter and the
      insertion element IS481), i.e. consensus PCR positive, or (ii) repeatably
      positive in only one assay. Using these criteria, 52 of 454 (11.5 %) samples were
      considered as PCR positive for B. pertussis. Six of 356 samples were culture
      positive for B. pertussis, 1/88 infants, 3/14 children and 2/254 contacts, giving
      an overall isolation rate of 1.7 %. Using these data, PCR gave an almost fivefold
      increase in diagnostic yield compared with culture (McNemar's test; P < 0.0001).
      Sera from 9/111 infants, 5/10 children and 14/210 contacts were positive.
      Serology and PCR results showed a high level of agreement (113/121) for infants
      and children. PCR demonstrated a significant improvement in diagnostic yield over
      culture. Serological testing also resulted in a significant increase in
      diagnostic yield compared to culture alone. PCR is a useful technique, but
      validity of results must be assured by careful control. Rapid diagnosis of B.
      pertussis infection particularly in infants by PCR, together with serological
      assays, can enhance surveillance systems for pertussis in all age groups.

PMID- 15150333
TI  - Prevalence, serotype distribution, antibiotic susceptibility and genetic profiles
      of mesophilic Aeromonas species isolated from hospitalized diarrhoeal cases in
      Kolkata, India.
AB  - A comprehensive study was performed to examine incidence, species distribution,
      drugs sensitivity, virulence genes and molecular fingerprints of Aeromonas
      species isolated from patients with acute diarrhoea over a period of 2 years in
      Kolkata, India. Following the Aerokey II scheme, more than 95 % of strains were
      identified to species level. Seven different species were encountered in this
      study, with Aeromonas caviae being dominant, followed by Aeromonas hydrophila and
      Aeromonas veronii biovar sobria. Thirty different serotypes were encountered,
      with O16, O83 and O85 being dominant, but no serotype was associated specifically
      with a single species. The majority of Aeromonas strains exhibited multidrug
      resistance. The alt and act genes, which encode heat-labile cytotonic and
      cytotoxic enterotoxins, were respectively found in 71.9 and 20.1 % of strains
      examined. Only 2.4 % of strains carried the heat-stable cytotonic enterotoxin
      (ast) gene. The hlyA gene was found in 28 % of Aeromonas strains. With few
      exceptions, genomic diversity of Aeromonas strains belonging to the same serotype
      was observed by random amplification of polymorphic DNA PCR and ribotyping.
      Different species of Aeromonas and different clones of Aeromonas species seem to
      be associated with hospitalized cases of diarrhoea in Kolkata, India.

PMID- 15150331
TI  - Antigenic and/or phase variation of PorA protein in non-subtypable Neisseria
      meningitidis strains isolated in Spain.
AB  - The PorA protein is a potential candidate as a vaccine component against
      meningococcal disease. However, this protein experiences antigenic variation and
      is subject to phase variations to evade immune selective pressure. In this study,
      the mechanisms responsible for altered expression of the PorA protein were
      analysed in 50 non-subtypable strains isolated from patients with meningococcal
      disease in Spain. The porA gene was amplified from 47 of the 50 strains. The
      majority of isolates were not recognized by the subtyping panel, as a result of
      non-synonymous base changes in the variable regions of the porA gene. Two of
      these strains revealed a premature stop codon before the variable region VR1 of
      PorA due to a single base-pair substitution at position 109 of the porA coding
      region. Another two presented a homopolymeric tract of eight adenine residues in
      the coding region, producing a DNA strand-slippage mechanism and PorA phase
      variation.

PMID- 15150335
TI  - Frequency and polymorphism of sopE in isolates of Salmonella enterica belonging
      to the ten most prevalent serotypes in England and Wales.
AB  - Translocated effector protein, SopE, leads to actin cytoskeletal rearrangements
      and membrane ruffling. Only a subset of Salmonella enterica serotypes possess
      sopE, with the majority of sopE-carrying S. enterica serotype Typhimurium
      associated with epidemics. Using real-time PCR and sequencing, sopE was
      investigated in the ten most prevalent serotypes of S. enterica in England and
      Wales in 2001. sopE was identified in S. Typhimurium definitive phage types 29,
      44, 49, 204b and 204c, all of which either have been involved in major epidemics
      or are precursors of epidemic strains. The presence of sopE varied in the
      remaining nine serotypes, but was more common in the top four (Enteritidis,
      Virchow, Hadar and Newport). Nucleotide changes were detected throughout sopE and
      may result in altered specificity for certain signal transduction pathways. Since
      acquisition of sopE may play a key role in emergence of epidemic strains,
      detection of sopE could aid identification of those Salmonella strains with the
      potential for epidemic spread.

PMID- 15150334
TI  - Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK,
      1991-2001.
AB  - Helicobacter pylori infection causes a number of gastrointestinal diseases and
      its current treatment is based on multidrug regimes including acid suppression
      and antimicrobials. The success of these regimes is determined by a number of
      factors including antibiotic resistance, which varies widely but is an increasing
      problem. Local data are important in establishing the most cost-effective
      eradication regime. Data have been collected prospectively on antibiotic
      resistance at Ipswich Hospital (Suffolk, UK) in all consecutive isolates of H.
      pylori from 1991 to 2001. The success of regimes consisting of a proton pump
      inhibitor, amoxycillin and metronidazole (PPI/A/M) has also been evaluated in
      patients found positive on serological testing in primary care using urea breath
      testing. Overall, metronidazole resistance was found in 31.7 % of isolates and
      clarithromycin resistance in 5.3 %. A significant increase in metronidazole
      resistance from 29.1 to 37.0 % (P = 0.022) and a decrease in clarithromycin
      resistance from 10.3 to 3.8 % (P = 0.014) was seen over the study period.
      Metronidazole resistance was significantly more common in women (P < 0.001) and
      young patients (P < 0.001). Eradication with PPI/A/M was successful in 89.9 % of
      patients and did not change significantly over the study period. Eradication
      rates were lower in young patients (P < 0.001). Whilst metronidazole resistance
      is increasing in Suffolk, this does not seem to have a significant effect on
      eradication rates. Metronidazole-based regimes are still effective first-line
      treatments in most patients.

PMID- 15150336
TI  - Genetic polymorphism of the accessory gene regulator (agr) locus in
      Staphylococcus epidermidis and its association with pathogenicity.
AB  - Staphylococcus epidermidis has become one of the most important causes of
      nosocomial infections in recent years. The staphylococcal accessory gene
      regulator (agr) is the most important locus responsible for the regulation of
      virulence factors, and it has been shown to be polymorphic. The aim of this study
      was to investigate the agr locus and its genetic polymorphisms in different
      Chinese S. epidermidis isolates and the relationship between genetic
      polymorphisms and pathogenicity. Specific PCR was used to amplify the different
      agr groups. Results were confirmed by restriction enzyme digestion and sequence
      analysis. agr mutations were detected and three agr groups of S. epidermidis were
      determined. Of the isolates, 12 % were pathogenic S. epidermidis and 17 % had
      naturally occurring agr mutations (P > 0.05). Pathogenic S. epidermidis isolates
      comprised 68.2 % agr group I, 19.3 % group II and 12.5 % group III, while
      isolates from healthy controls comprised 39 % agr group I, 51 % group II and 10 %
      group III (P < 0.01). The percentages of agr locus mutants and the three agr
      groups in different hospitals showed no significant differences (P > 0.05). The
      percentage of agr group I S. epidermidis isolated from catheters and blood was
      higher than that isolated from the other clinical specimens. This is the first
      study to investigate the genetic polymorphism of agr in S. epidermidis in China.
      The mean percentage of agr locus mutants was 14.9 % (12 % in clinical specimens;
      17.7 % in controls). Genetic polymorphism of agr in S. epidermidis was linked to
      its pathogenicity; group I was associated with pathogenicity, while most isolates
      from healthy subjects were group II. The mechanism is to be investigated.

PMID- 15150337
TI  - Inhibition of Clostridium difficile strains by intestinal Lactobacillus species.
AB  - Indigenous intestinal microflora (including lactobacilli) has an important role
      in protection against Clostridium difficile infection. To assess in vitro
      interaction between lactobacilli and C. difficile, antagonistic activity of 50
      intestinal Lactobacillus spp. strains against 23 pathogenic C. difficile strains
      was determined. Phenotypic properties of C. difficile strains [production of
      short-chain fatty acids (SCFAs) and toxin A, and antimicrobial susceptibility]
      and lactobacilli (production of SCFAs and H(2)O(2)) were investigated. Five
      lactobacilli (Lactobacillus paracasei and Lactobacillus plantarum species) were
      antagonistic to all C. difficile strains, 18 were antagonistic to some C.
      difficile strains and 27 showed no antagonistic activity. This antagonistic
      activity was strain-specific and seemed to correlate with H(2)O(2) and lactic
      acid production. C. difficile strains that were more sensitive to lactobacilli (n
      = 9) usually produced higher toxin levels and more SCFAs, and were more resistant
      to antibiotics, than strains that were resistant to lactobacilli (n = 14).
      Compatibility of C. difficile strain properties (resistance to lactobacilli or
      antibiotics) with intestinal microecological conditions (e.g. presence of
      antagonistic lactobacilli, concentration of antibiotics) may determine expression
      of disease.

PMID- 15150338
TI  - Wound botulism in the UK and Ireland.
AB  - There are three main, naturally occurring, epidemiological types of botulism:
      food-borne, intestinal colonization (infant botulism) and wound botulism. The
      neurological signs and symptoms are the same for all three epidemiological types
      and may include respiratory paralysis. Wound botulism is caused by growth of
      cells and release of toxin in vivo, is associated with traumatic wounds and
      abscesses and has been reported in drug users, such as those injecting heroin or
      sniffing cocaine. Up to the end of 1999 there were no confirmed cases of wound
      botulism in the UK. Between the beginning of 2000 and the end of December 2002,
      there were 33 clinically diagnosed cases of wound botulism in the UK and Ireland.
      All cases had injected heroin into muscle or by 'skin popping'. The clinical
      diagnosis was confirmed by laboratory tests in 20 of these cases. Eighteen cases
      were caused by type A toxin and two by type B toxin.

PMID- 15150339
TI  - Changes in oral microbial profiles after periodontal treatment as determined by
      molecular analysis of 16S rRNA genes.
AB  - Terminal RFLP (T-RFLP) analysis was used to investigate changes in the oral
      microbiota in saliva and subgingival plaque samples from one patient with
      aggressive periodontitis (subject A) and two patients with chronic periodontitis
      (subjects B and C) before and 3 months after periodontal treatment. Substantial
      changes in the T-RFLP patterns of subgingival plaque samples of subjects B and C
      were noted after 3 months of improved oral hygiene and full-mouth supra- and
      subgingival scaling and root planing. However, there was little change in the
      subgingival microbiota of subject A. Although the proportions of terminal
      restriction fragments (T-RFs) larger than 1000 bp were notable in the T-RFLP
      patterns generated after digestion with HhaI of the samples from two subjects
      before treatment (subject B, 35.5 %; subject C, 29.6 %), the proportions of these
      T-RFs were significantly reduced or not detected after treatment (subject B,
      none; subject C, 4.1 %). Real-time PCR showed a significant change in the
      proportions of target bacteria in subgingival plaque samples of subject B. After
      3 months, the Porphyromonas gingivalis population was markedly reduced (3.1 x 10(
      3) %), whereas the proportion of Porphyromonas gingivalis before treatment was
      7.6 %. The proportions of Tannerella forsythensis, Treponema denticola and
      Treponema socranskii were also markedly diminished after treatment. Similarly,
      the proportion of the T-RF presumed to represent Porphyromonas gingivalis was 5.9
      % and became undetectable after 3 months. Analysis of 16S rRNA gene clone
      libraries from subgingival plaque samples of subject B before and after treatment
      showed a notable change in the subgingival microbiota. These results were in
      agreement with the T-RFLP analysis data and showed that the T-RFs larger than
      1000 bp represent Peptostreptococcus species. Our results indicate that T-RFLP
      analysis is useful for evaluation of the effects of medical treatment of
      periodontitis.

PMID- 15150340
TI  - Phenotypic and functional characterization of intraepithelial lymphocytes in a
      bovine ligated intestinal loop model of enterohaemorrhagic Escherichia coli
      infection.
AB  - Ruminants are a major reservoir of enterohaemorrhagic Escherichia coli (EHEC),
      which cause acute gastroenteritis in humans with potentially life-threatening
      sequelae. The mechanisms underlying EHEC persistence in ruminant hosts are poorly
      understood. EHEC produce several cytotoxins that inhibit the proliferation of
      bovine lymphocytes in vitro and influence EHEC persistence in calves, suggesting
      that bacterial suppression of mucosal inflammation may be important in vivo. In
      order to address this hypothesis, intraepithelial lymphocytes (IEL) obtained from
      ligated intestinal loops of five 9-14 day old calves were characterized 12 h
      after inoculation with E. coli strains. Loops were inoculated with an EHEC O103 :
      H2 strain, an isogenic Deltastx1 mutant incapable of producing Shiga toxin 1
      (Stx1) and a porcine non-pathogenic E. coli strain. The IEL mainly comprised
      activated CD2(+) CD3(+) CD6(+) CD8alpha(+) T cells and resembled IEL obtained
      from the intestinal mucosa of orally challenged calves. Forty per cent of all IEL
      were potentially sensitive to Stx1 in that they expressed the receptor for Stx1.
      Nevertheless, analysis of IEL from inoculated loops failed to detect a
      significant effect of the different E. coli strains on proliferative capacity,
      natural killer cell activity or the cytokine mRNA profile. However, the EHEC wild
      type strain reduced the percentage of CD8alpha(+) T cells in the ileal mucosa
      compared with loops inoculated with the Deltastx1 mutant. This shift in IEL
      composition was not associated with inhibition of IEL proliferation in situ,
      since the majority of the IEL from all loops were in the G(0)/G(1) phase of the
      cell cycle. These studies indicate that the ligated ileal loop model will be a
      useful tool to dissect the mechanisms underlying suppression of mucosal
      inflammation by EHEC in the reservoir host.

PMID- 15150341
TI  - Clostridium fallax associated with sudden death in a 16-year-old boy.
AB  - Clostridial myonecrosis or gas gangrene occurs most frequently in contaminated
      wounds following trauma or surgery. It is caused by a wide variety of Clostridium
      species, the most common being Clostridium perfringens. Spontaneous, non
      traumatic clostridial myonecrosis is uncommon and is usually associated with
      gastrointestinal and haematological malignancy, diabetes mellitus and peripheral
      vascular disease. The case of a previously healthy 16-year-old boy with acute
      onset of gastrointestinal symptoms, who died of bacterial sepsis without apparent
      preceding trauma, is presented here. Clostridium fallax was identified as the
      most probable causative agent. As far as is known, this is the first report of
      fatal sepsis in humans due to C. fallax, which has been described only rarely as
      a cause of gas oedema in animals.

PMID- 15150342
TI  - DNA repair in higher plants; photoreactivation is the major DNA repair pathway in
      non-proliferating cells while excision repair (nucleotide excision repair and
      base excision repair) is active in proliferating cells.
AB  - We investigated expression patterns of DNA repair genes such as the CPD
      photolyase, UV-DDB1, CSB, PCNA, RPA32 and FEN-1 genes by northern hybridization
      analysis and in situ hybridization using a higher plant, rice (Oryza sativa L.
      cv. Nipponbare). We found that all the genes tested were expressed in tissues
      rich in proliferating cells, but only CPD photolyase was expressed in non
      proliferating tissue such as the mature leaves and elongation zone of root. The
      removal of DNA damage, cyclobutane pyrimidine dimers and (6-4) photoproducts, in
      both mature leaves and the root apical meristem (RAM) was observed after UV
      irradiation under light. In the dark, DNA damage in mature leaves was not
      repaired efficiently, but that in the RAM was removed rapidly. Using a rice 22K
      custom oligo DNA microarray, we compared global gene expression patterns in the
      shoot apical meristem (SAM) and mature leaves. Most of the excision repair genes
      were more strongly expressed in SAM. These results suggested that
      photoreactivation is the major DNA repair pathway for the major UV-induced damage
      in non-proliferating cells, while both photoreactivation and excision repair are
      active in proliferating cells.

PMID- 15150343
TI  - A minimalist glutamyl-tRNA synthetase dedicated to aminoacylation of the tRNAAsp
      QUC anticodon.
AB  - Escherichia coli encodes YadB, a protein displaying 34% identity with the
      catalytic core of glutamyl-tRNA synthetase but lacking the anticodon-binding
      domain. We show that YadB is a tRNA modifying enzyme that evidently glutamylates
      the queuosine residue, a modified nucleoside at the wobble position of the
      tRNA(Asp) QUC anticodon. This conclusion is supported by a variety of biochemical
      data and by the inability of the enzyme to glutamylate tRNA(Asp) isolated from an
      E.coli tRNA-guanosine transglycosylase minus strain deprived of the capacity to
      exchange guanosine 34 with queuosine. Structural mimicry between the tRNA(Asp)
      anticodon stem and the tRNA(Glu) amino acid acceptor stem in prokaryotes encoding
      YadB proteins indicates that the function of these tRNA modifying enzymes, which
      we rename glutamyl-Q tRNA(Asp) synthetases, is conserved among prokaryotes.

PMID- 15150344
TI  - Visualization of inositol phosphate-dependent mobility of Ku: depletion of the
      DNA-PK cofactor InsP6 inhibits Ku mobility.
AB  - Repair of DNA double-strand breaks (DSBs) in mammalian cells by nonhomologous end
      joining (NHEJ) is initiated by the DNA-PK protein complex. Recent studies have
      shown inositol hexakisphosphate (InsP6) is a potent cofactor for DNA-PK activity
      in NHEJ. Specifically, InsP6 binds to the Ku component of DNA-PK, where it
      induces a conformational change and a corresponding increase in DNA end-joining
      activity. However, the effect of InsP6 on the dynamics of Ku, such as its
      mobility in the nucleus, is unknown. Importantly, these dynamics reflect the
      character of Ku's interactions with other molecules. To address this question,
      the diffusion of Ku was measured by fluorescence photobleaching experiments using
      cells expressing green fluorescent protein (GFP)-labeled Ku. InsP6 was depleted
      by treating cells with calmodulin inhibitors, which included the compounds W7 and
      chlorpromazine. These treatments caused a 50% reduction in the mobile fraction of
      Ku-GFP, and this could be reversed by replenishing cells with InsP6. By
      expressing deletion mutants of Ku-GFP, it was determined that its W7-sensitive
      region occurred at the N-terminus of the dimerization domain of Ku70. These
      results therefore show that InsP6 enhances Ku mobility through a discrete region
      of Ku70, and modulation of InsP6 levels in cells represents a potential avenue
      for regulating NHEJ by affecting the dynamics of Ku and hence its interaction
      with other nuclear proteins.

PMID- 15150346
TI  - Neuropsychological performance after kidney transplantation: a comparison between
      transplant types and in relation to dialysis and normative data.
AB  - BACKGROUND: Neuropsychological (NP) performance after kidney transplantation (TX)
      has received little attention. This study compared NP functioning between
      dialysis and transplant patients and between living-related donor (LRD) and
      cadaver (CAD) transplant recipients. The association between immunosuppressive
      medication and NP outcomes was also examined. METHODS: One hundred and seventeen
      transplant recipients (25 LRD and 92 CAD patients) and 145 dialysis patients (77
      haemodialysis and 68 peritoneal dialysis) were administered an NP test battery to
      assess learning and verbal recall, attention and concentration, and psychomotor
      abilities/speed. Biochemical markers of renal function were also assessed.
      RESULTS: Overall, transplant patients showed normal cognitive functioning in all
      domains assessed. NP performance was found to be equivalent in both transplant
      groups and in patients on cyclosporin and those on tacrolimus. ANCOVAs showed
      that TX patients performed significantly better than dialysis patients on
      selective NP tests, i.e. the two memory tasks and two out of the four tests of
      attention. No differences were found in motor tasks. CONCLUSIONS: Our results
      reveal no evidence of NP deficits in TX patients. The NP advantage of TX relative
      to dialysis is evident mainly in verbal memory.

PMID- 15150345
TI  - Changes in renal function in patients with familial amyloid polyneuropathy
      treated with orthotopic liver transplantation.
AB  - BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomal dominant
      disease caused by a point mutation in the gene encoding transthyretin, which is
      secreted by the liver. Orthotopic liver transplantation (OLT) has been proposed
      to prevent disease progression. Little is known about long-term changes in renal
      function and lesions after OLT. METHODS: The renal function of 33 patients with
      FAP was evaluated (proteinuria, serum creatinine, creatinine clearance) before
      OLT and over a period of at least 5 years afterwards. A pre-transplantation renal
      biopsy was performed in 14 patients and a follow-up biopsy in eight patients.
      RESULTS: Before transplantation, mean serum creatinine concentration was 86
      micromol/l (47-126 micromol/l) and creatinine clearance was 71.9+/-31.6
      ml/min/1.73 m(2). Proteinuria was detected in 54% of patients (0.3-4 g/day). Pre
      transplant renal biopsies (n = 14) revealed glomerular, tubular and vascular
      amyloid deposits in 90, 58 and 66% of patients, respectively. Eleven patients
      (33%) died after OLT. Death occurred most frequently in patients having weight
      losses >7 kg (P<0.05). After transplantation, 25 patients (76%) suffered acute
      renal failure but only one required dialysis. One month after transplantation,
      the mean serum creatinine concentration was 134.1+/-73 micromol/l and remained
      constant during follow-up. Eight patients underwent a second renal biopsy 2 years
      after transplantation. No significant changes in deposits or renal toxicity due
      to calcineurin inhibitors were detected. CONCLUSION: Although liver
      transplantation in FAP does not affect existing renal amyloid deposits, it
      prevents the progression of renal disease.

PMID- 15150347
TI  - Malnutrition and inflammation are associated with impaired pulmonary function in
      patients with chronic kidney disease.
AB  - BACKGROUND: Inflammation and malnutrition are common findings in patients with
      chronic kidney disease (CKD). We hypothesized that in inflamed and malnourished
      patients, respiratory and peripheral muscle dysfunction may have significant
      consequences on pulmonary function. The aim of this study was to investigate
      possible associations between pulmonary function and inflammation and
      malnutrition in patients with CKD. METHODS: We studied 109 patients (63% males;
      53+/-12 years) at the initiation of dialysis treatment (GFR 7.5+/-2.5 ml/min).
      Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital
      capacity (FVC) and peak expiratory flow (PEF)] were performed and the percentages
      of predicted values were calculated (%FEV(1), %FVC and %PEF). Systemic
      inflammation, assessed by high-sensitivity C-reactive protein (hsCRP) and
      nutritional status assessed by subjective global assessment (SGA), lean body mass
      (LBM) (estimated with dual energy X-ray absorptiometry) and hand-grip strength
      (HGS), were evaluated at the same time. RESULTS: Significant negative
      correlations were found between hsCRP and the percent predicted values for all
      pulmonary function tests [%FEV(1) (Rho = -0.45), %FVC (Rho = -0.43) and %PEF (Rho
      = -0.38)], respectively. Malnourished patients defined as SGA >or=2 had lower
      %FEV(1) (64+/-19 vs 82+/-23%; P<0.001) and %FVC (67+/-18 vs 83+/-21%; P<0.001)
      than well nourished patients. Significant correlations were observed between HGS
      and %FVC (Rho = 0.38; P <0.001), %FEV(1) (Rho = 0.37; P<0.001) and %PEF (Rho =
      0.22; P<0.05) and between LBM and %PEF (Rho = 0.20; P<0.05). Multivariate Cox
      analysis showed that cardiovascular disease and low %FVC were associated with
      poor survival. CONCLUSIONS: Impaired pulmonary function is associated with
      malnutrition and inflammation, and predicts mortality in CKD patients. This may
      reflect an impact of malnutrition and inflammation on respiratory muscle
      performance, leading to pulmonary dysfunction, which could influence the clinical
      outcome.

PMID- 15150348
TI  - A prospective proof of concept study of the efficacy of tacrolimus ointment on
      uraemic pruritus (UP) in patients on chronic dialysis therapy.
AB  - BACKGROUND: Uraemic pruritus (UP) is a serious symptom of chronic dialysis
      patients and patients with end-stage renal disease. UP causes skin damage,
      discomfort, sleeping disorders and diminished quality of life. Since UP is
      considered to be in part an immune-mediated inflammatory process,
      immunosuppressive drugs like tacrolimus may be beneficial. METHODS: We conducted
      a prospective study on the effect of 6 weeks treatment with two sequential
      concentrations of tacrolimus ointment on the severity of UP in chronic dialysis
      patients and again after 2 weeks wash-out. Twenty-five patients with UP were
      enrolled in the study; 21 patients completed the study. UP was measured using a
      validated modified pruritus assessment score and a Visual Analogue Scale (VAS).
      RESULTS: The modified pruritus assessment score decreased significantly by 81.8%
      after 6 weeks treatment from [median score 11 (interquartile range: IQR 6-16) on
      day 0 to median score 2 (IQR 0-5.25) at week 6: P<0.0001]. After 2 weeks wash
      out, the median score returned to 72.7% of baseline levels [8 (IQR 2-16)]. Using
      the VAS score an identical evolution could be demonstrated. Tacrolimus ointment
      was well tolerated and no serious adverse events were noted. Transient stinging
      and burning sensation was reported by four patients in the first weeks of the
      trial, one patient suffered a mild skin rash. No systemic exposure to tacrolimus
      was detected. CONCLUSION: This prospective study has shown that 6 weeks treatment
      with tacrolimus ointment significantly reduces the severity of UP in chronic
      dialysis patients and is well tolerated. Randomized placebo-controlled studies
      are necessary to confirm these encouraging preliminary results.

PMID- 15150349
TI  - Secretion of collagen type IV by human renal fibroblasts is increased by high
      glucose via a TGF-beta-independent pathway.
AB  - BACKGROUND: Tubulointerstitial fibrosis is an important component of diabetic
      nephropathy, which is characterized by increased expression of interstitial
      extracellular matrix components and aberrant expression of the basement membrane
      component collagen type IV. The present study examined the effect of high ambient
      glucose and transforming growth factor-beta1 (TGF-beta1) on collagen secretion by
      human renal fibroblasts and proximal tubular epithelial cells (PTECs). METHODS:
      Human renal fibroblasts (TK173) and PTECs (HK2) were used to examine the effects
      of high glucose (25 mM d-glucose) and TGF-beta1 (1 ng/ml) on collagen type I, III
      and IV secretion compared with control medium (5.5 mM glucose). Matrix components
      were measured by enzyme-linked immunosorbent assay (ELISA) and reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Renal fibroblasts are
      the main producers of the interstitial components collagen type I and type III,
      while collagen type IV was secreted predominantly by PTECs. However, renal
      fibroblasts were also able to secrete collagen type IV. Secretion of collagen
      type IV by fibroblasts was increased upon stimulation with TGF-beta1, reaching
      levels comparable with those secreted by TGF-beta1-induced PTECs. Moreover, high
      glucose stimulated increased collagen type IV secretion. Importantly, this could
      not be attenuated by neutralizing pan-specific anti-TGF-beta antibodies.
      CONCLUSIONS: These data show that renal fibroblasts secrete collagen type IV,
      which can be increased by high glucose independent of endogenous TGF-beta. This
      suggests that as well as the increased expression of interstitial components,
      renal fibroblasts can contribute to the increased expression of the basement
      membrane component collagen type IV in tubulointerstitial fibrosis observed
      during diabetic nephropathy.

PMID- 15150350
TI  - Serum levels of macrophage-colony stimulating factor (M-CSF): a marker of kidney
      allograft rejection.
AB  - BACKGROUND: Macrophage-colony stimulating factor (M-CSF) is the principal factor
      for survival of monocytes and macrophages that play an important role in
      allograft rejection. We studied M-CSF serum levels during successful renal
      transplantation and acute graft rejection. METHODS: A total of 114 kidney
      allograft recipients were assessed for M-CSF levels by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: M-CSF serum levels were elevated in pre
      transplant haemodialysis patients (611+/-355 IU/ml vs 168+/-61 in normal
      controls, P<0.01). Following successful renal transplantation, M-CSF decreased in
      the first month, stabilizing at 257+/-222 IU/ml (not significantly different from
      normal controls) in 52 post-transplant stable patients. There was no correlation
      between M-CSF level and creatinine clearance. M-CSF levels increased
      significantly (2-5 times) during biopsy-proven acute rejection episodes in 20 of
      25 patients. All rejection episodes were successfully treated and serum M-CSF
      decreased rapidly to pre-rejection levels in 17/20 patients. In contrast, in five
      patients with cyclosporin toxicity and four patients with other causes of
      allograft dysfunction, M-CSF serum levels did not change. CONCLUSIONS: M-CSF
      serum level might be a specific marker of acute rejection. The source of
      increased production during rejection warrants further investigation, with
      infiltrating T cells and resident kidney cells being likely candidates.

PMID- 15150351
TI  - Methylglyoxal: a stimulus to neutrophil oxygen radical production in chronic
      renal failure?
AB  - BACKGROUND: Chronic renal failure is characterized by oxidant stress, resulting
      in part from increased reactive oxygen species production by neutrophils. Plasma
      concentrations of methylglyoxal are increased in uraemia. Methylglyoxal activates
      p38 mitogen-activated protein kinase (MAPK) in endothelial cells. Activation of
      p38 MAPK in neutrophils enhances reactive oxygen species production through
      exocytosis of intracellular storage granules. We tested the hypothesis that
      methylglyoxal enhances reactive oxygen species production by activating p38 MAPK
      in neutrophils. METHODS: Neutrophils were exposed to methylglyoxal in vitro.
      Activation of p38 MAPK was determined by immunoblot analysis. Exocytosis was
      determined by measuring plasma membrane expression of CD35 and CD66b, specific
      markers of secretory vesicles and specific granules, respectively. Reactive
      oxygen species production was determined by measuring H(2)O(2) and O(-)(2)
      production. RESULTS: Methylglyoxal activated p38 MAPK and caused dose-dependent
      increases in CD35 and CD66b expression, which were blocked by the methylglyoxal
      scavenger, aminoguanidine, or the p38 MAPK inhibitor, SB203580. Methylglyoxal
      caused dose-dependent increases in basal and Staphylococcus aureus-stimulated
      H(2)O(2) production and basal and formyl-methionyl-leucyl-phenylalanine
      stimulated O(-)(2) production. Enhancement of reactive oxygen species production
      was blocked by aminoguanidine and SB203580. CONCLUSIONS: Methylglyoxal enhances
      reactive oxygen species production in neutrophils through a process involving p38
      MAPK-dependent exocytosis of intracellular storage granules. These findings,
      together with the observation that methylglyoxal concentrations are increased in
      renal failure, suggest a possible role for methylglyoxal as a uraemic toxin that
      contributes to the oxidant stress associated with renal failure.

PMID- 15150352
TI  - Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice.
AB  - BACKGROUND: Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody
      (MPO-ANCA) has been a useful diagnostic marker in systemic vasculitis with
      crescentic glomerulonephritis (CrGN). It is highly suspected that the antigenic
      enzyme MPO released from activated neutrophils is involved in these lesions. We
      evaluated the relationship between neutrophil functions including peripheral
      neutrophil counts and renal lesions in SCG/Kj mice as a model of ANCA-associated
      CrGN and vasculitis. METHODS: Peripheral neutrophil counts, the plasma levels of
      MPO-ANCA and tumour necrosis factor alpha (TNF-alpha) were measured. The capacity
      of MPO release and superoxide generation were evaluated as neutrophil activity.
      The renal lesions were estimated by grade of proteinuria, histopathological
      lesion, such as glomerular neutrophil infiltration and active or chronic renal
      injury scores with crescent formation. RESULTS: MPO-ANCA and TNF-alpha levels
      were higher than those of normal mice C57BL/6 even before overt proteinuria;
      subsequently, peripheral neutrophils increased. In the phase of nephritis with
      low grade proteinuria, the spontaneous release of MPO from peripheral neutrophils
      increased, while superoxide generation increased before spontaneous MPO release
      occurred. In addition, the renal lesion in histological observations was
      aggravated with ageing and the glomerular neutrophil infiltration was positively
      correlated with MPO-ANCA levels, as well as with histological indices of
      nephritis, active renal injury score; in particular, crescent formation was
      correlated with spontaneous MPO release. In contrast, superoxide generation was
      negatively correlated with the severity of this lesion during the progression.
      CONCLUSIONS: These findings indicate that neutrophils are activated and
      contribute to the development of the active crescentic lesion in SCG/Kj mice.

PMID- 15150353
TI  - Left ventricular hypertrophy after renal transplantation: new approach to a
      deadly disorder.

PMID- 15150354
TI  - Exercise-induced acute renal failure associated with renal hypouricaemia: results
      of a questionnaire-based survey in Japan.
AB  - BACKGROUND: A retrospective investigation was conducted to define the clinical
      features of exercise-induced acute renal failure (ARF) associated with renal
      hypouricaemia with the aim of clarifying further the clinical features of the
      disease entity. METHODS: A questionnaire was mailed to 43 institutions in Japan
      that had experienced case(s) of exercise-induced ARF associated with renal
      hypouricaemia. Fifty-four patients (48 males and six females) were identified
      from 38 institutions. RESULTS: Median age at the first episode of ARF was 17
      years (range 11-46). The maximal serum uric acid and creatinine levels were
      4.40+/-2.49 (range 0.4-13.3) and 5.45+/-3.33 mg/dl (range 1.10-17.7),
      respectively. The serum uric acid level after recovery was 0.70+/-0.25 mg/dl
      (range 0.1-1.4). The short-term prognosis seemed to be good and histological
      findings in 28 patients showed minimal change or acute tubular necrosis except
      for one patient with chronic lesions. ARF episodes occurred predominantly in
      September, October and May, mostly after strenuous exercise such as a short
      distance race. The first symptoms were nausea/vomiting in 51 episodes, loin pain
      in 35, abdominal pain in 22, general fatigue in 16 and low-grade fever in seven.
      Thirteen patients (24.1%) experienced recurrent ARF at various intervals.
      Univariate and multivariate analyses failed to demonstrate any risk factor of ARF
      recurrence, although no female patients experienced ARF recurrence. CONCLUSIONS:
      The reason for the heterogeneity in ARF associated with renal hypouricaemia
      remains unknown. Further studies, especially on molecular mechanisms, are
      required to establish the best guidance against ARF recurrence.

PMID- 15150355
TI  - The haemodynamic response to submaximal exercise during isovolaemic
      haemodialysis.
AB  - INTRODUCTION: Exercise during haemodialysis has potential benefits but may
      compromise cardiovascular stability. We studied its acute effects on relative
      blood volume (RBV) and other haemodynamic parameters. METHODS: Two groups of 10
      patients were exercised submaximally using a stationary cycle during isovolaemic
      dialysis whilst RBV was monitored continuously. In study 1, patients exercised
      for two 10 min periods separated by 10 min rest. Cardiac output (CO), peripheral
      vascular resistance (PVR), central blood volume (CBV) and stroke volume were
      measured using ultrasound dilution immediately before and after each exercise
      session. In study 2, haemoglobin, serum total protein and albumin levels were
      measured before and immediately after the exercise session and at the nadir of
      the RBV trace. RESULTS: RBV fell immediately on exercise initiation, the maximum
      reduction being 2.0+/-1.1% (after 5.9+/-1.4 min of exercise 1: P<0.001) and 2.0+/
      1.2% (after 4.7+/-2.3 min of exercise 2: P<0.001). CO increased significantly
      after both periods of exercise (4.5+/-0.96 and 5.1+/-1.1 to 7.2+/-2.1 and 7.9+/
      2.4 l/min, P<0.001 in both). Stroke volume increased significantly and PVR fell
      significantly during exercise. CBV increased in absolute terms but fell as a
      proportion of CO. Mean haemoglobin level at the RBV nadir was significantly
      higher than baseline (12.3+/-1.8 vs 11.8+/-1.7 g/dl: P<0.05: mean change 4.4+/
      2.3%), as was mean total protein concentration (66.0+/-6.9 vs 62.0+/-8.1 g/l: P =
      0.001: mean change 6.8+/-5.9%) and mean serum albumin concentration (36.0+/-3.9
      vs 34.1+/-3.9 g/l: P<0.001: mean change 5.8+/-3.5%). CONCLUSION: The haemodynamic
      response to exercise during haemodialysis is comparable with that in normal
      individuals. The rapid reduction in RBV on exercise occurs in spite of a
      significant increase in CO, mainly as a consequence of fluid shifts from the
      microvasculature to the interstitium.

PMID- 15150356
TI  - On the relative safety of parenteral iron formulations.
AB  - BACKGROUND: Intravenous iron is usually required to optimize the correction of
      anaemia in persons with advanced chronic kidney disease and end-stage renal
      disease. Randomized clinical trials may have insufficient power to detect
      differences in the safety profiles of specific formulations. METHODS: We obtained
      data from the US Food and Drug Administration on reported adverse drug events
      (ADEs) related to the provision of three formulations of intravenous iron during
      1998-2000. We estimated the relative risks [odds ratios (OR)] of ADEs associated
      with the use of higher molecular weight iron dextran and sodium ferric gluconate
      complex compared with lower molecular weight iron dextran using 2 x 2 tables.
      RESULTS: The total number of reported parenteral iron-related ADEs was 1981 among
      approximately 21,060,000 doses administered, yielding a rate of 9.4 x 10(-5), or
      approximately 94 per million. Total major ADEs were significantly increased among
      recipients of higher molecular weight iron dextran (OR 5.5, 95% CI 4.9-6.0) and
      sodium ferric gluconate complex (OR 6.2, 95% CI 5.4-7.2) compared with recipients
      of lower molecular weight iron dextran. We observed significantly higher rates of
      life-threatening ADEs, including death, anaphylactoid reaction, cardiac arrest
      and respiratory depression among users of higher molecular weight compared with
      lower molecular weight iron dextran. There was insufficient power to detect
      differences in life-threatening ADEs when comparing lower molecular weight iron
      dextran with sodium ferric gluconate complex. CONCLUSIONS: Parenteral iron
      related ADEs are rare. Using observational data, overall and most specific ADE
      rates were significantly higher among recipients of higher molecular weight iron
      dextran and sodium ferric gluconate complex than among recipients of lower
      molecular weight iron dextran. These data may help to guide clinical practice, as
      head-to-head clinical trials comparing different formulations of intravenous iron
      have not been conducted.

PMID- 15150357
TI  - A 33-year-old man with nephrotic syndrome and lecithin-cholesterol
      acyltransferase (LCAT) deficiency. Description of two new mutations in the LCAT
      gene.

PMID- 15150358
TI  - Acute interstitial nephritis in a case of Ascaris lumbricoides infection.

PMID- 15150359
TI  - Bilateral primary renal lymphoma treated by surgery and chemotherapy.

PMID- 15150361
TI  - Salvage of renal allograft using venous thrombectomy in the setting of
      iliofemoral venous thrombosis.

PMID- 15150360
TI  - High-risk dialysis: pregnancy in a patient with extended Stanford-B-aneurysm of
      the aorta and end-stage renal disease.

PMID- 15150362
TI  - Recurrence of sarcoidosis in renal allograft during pregnancy.

PMID- 15150363
TI  - The phosphorus connection--a puzzling business.

PMID- 15150364
TI  - A young renal transplant recipient with unexplained resting sinus tachycardia,
      hypertension and beta-blocker resistance.

PMID- 15150365
TI  - Anasarca secondary to problems in three organs: one man with three diseases?

PMID- 15150366
TI  - Persistent nephrogram after administration of an isoosmolar contrast medium.

PMID- 15150367
TI  - Digital ischaemia in a renal transplant patient.

PMID- 15150369
TI  - Vesicoureteral reflux and idiopathic hypercalciuria: an association by chance?

PMID- 15150368
TI  - Does dose matter?

PMID- 15150370
TI  - 1 alpha-hydroxy vitamin D3 and cardiovascular mortality.

PMID- 15150371
TI  - An acute renal failure patient successfully stented for bilateral renal artery
      occlusion with a distal embolism protection device.

PMID- 15150372
TI  - Conventional haemodialysis significantly lowers toxic levels of phenobarbital.

PMID- 15150373
TI  - Possible involvement of cross-linking advanced glycation endproducts in long-term
      CAPD peritoneal degeneration.

PMID- 15150374
TI  - Fructose-responsive genes in the small intestine of neonatal rats.
AB  - The intestinal brush border fructose transporter GLUT5 (SLC2A5) typically appears
      in rats after weaning is completed. However, precocious consumption of dietary
      fructose or in vivo perfusion for 4 h of the small intestine with high fructose
      (HF) specifically stimulates de novo synthesis of GLUT5 mRNA and protein before
      weaning is completed. Intermediary signals linking the substrate, fructose, to
      GLUT5 transcription are not known but should also respond to fructose perfusion.
      Hence, we used microarray hybridization and RT-PCR to identify genes whose
      expression levels change during HF relative to high-glucose (HG) perfusion.
      Expression of GLUT5 and NaPi2b, the intestinal Na+-dependent phosphate
      transporter, dramatically increased and decreased, respectively, with HF
      perfusion for 4 h. Expression of >20 genes, including two key gluconeogenic
      enzymes, glucose-6-phosphatase (G6P) and fructose-1,6-bisphosphatase, also
      increased markedly, along with fructose-2,6-bisphosphatase, an enzyme unique to
      fructose metabolism and regulating fructose-1,6-bisphosphatase activity. GLUT5
      and G6P mRNA abundance, which increased dramatically with HF relative to HG,
      alpha-methylglucose, and normal Ringer perfusion, may be tightly and specifically
      linked to changes in intestinal luminal fructose but not glucose concentrations.
      G6P but not GLUT5 mRNA abundance increased after just 20 min of HF perfusion.
      This cluster of gluconeogenic enzymes and their common metabolic intermediate
      fructose-6-phosphate may regulate fructose metabolism and GLUT5 expression in the
      small intestine.

PMID- 15150375
TI  - Accuracy of abstracts for original research articles in pharmacy journals.
AB  - BACKGROUND: Accuracy of abstracts representing original research articles is
      imperative since these are readily available and biomedical literature readers
      may not have access to the full-text article. Furthermore, previous reports
      document discrepancies in published original research abstracts compared with the
      full-text article. OBJECTIVE: To determine the accuracy of abstracts for original
      research articles published in nationally represented, widely circulated pharmacy
      specific journals (American Journal of Health-System Pharmacy, The Annals of
      Pharmacotherapy, The Consultant Pharmacist, Hospital Pharmacy, Journal of the
      American Pharmacists Association, Pharmacotherapy: The Journal of Human
      Pharmacology and Drug Therapy) from June 2001 through May 2002. METHODS: Outcome
      measures included an omission, defined as data in the abstract not located in the
      article. In addition, abstracts were considered deficient if these included an
      omission, inaccurate factual (i.e., qualitative and quantitative) information
      presented in the abstract that differed from information contained within the
      text, an inconsistency in following the "Instructions for Authors" for the
      respective journal, or a discrepancy between the placement of text in the
      manuscript and a structured abstract. RESULTS: A total of 243 abstracts for
      original research articles were published in selected journal issues. Evaluation
      of these abstracts identified 60 (24.7%) abstracts containing omissions; 81
      (33.3%) abstracts contained either an omission or inaccuracy. A total of 147
      (60.5%) abstracts were classified as deficient. CONCLUSIONS: Results of this
      analysis demonstrate that improvements are needed within abstracts for original
      research articles published in pharmacy-specific journals. Authors and peer
      reviewers should analyze the abstract contents closely to ensure that the
      abstract accurately represents the full-text article.

PMID- 15150376
TI  - Clinical utilization of atypical antipsychotics in pregnancy and lactation.
AB  - OBJECTIVE: To analyze the available literature regarding the safety of atypical
      antipsychotics in pregnancy and lactation in order to recommend evidence-based
      strategies for pharmacologic management of psychosis in these conditions. DATA
      SOURCES: We summarized the results from articles identified via
      MEDLINE/PubMed/TOXNET (1993-January 31, 2004), using the key terms pregnancy,
      lactation, breast-feeding, human milk, psychotropic drugs, atypical
      antipsychotics, olanzapine, quetiapine, risperidone, clozapine, ziprasidone, and
      aripiprazole. STUDY SELECTION AND DATA EXTRACTION: Retrospective studies,
      clinical observations, and case reports regarding the 6 atypical antipsychotics
      mentioned above were selected and analyzed. Extensive manual review of pertinent
      journals and textbooks was also performed. DATA SYNTHESIS: Reviewed studies show
      that olanzapine and clozapine apparently do not increase the teratogenic risk if
      administered to pregnant women, while evidence on quetiapine, risperidone,
      aripiprazole, and ziprasidone is still limited. In contrast, available
      information is not able to exclude unwanted serious effects associated with the
      use of all atypical antipsychotics on mother-infant dyads. Furthermore, more than
      a few studies suggest increased hyperglycemic risk for pregnant women related to
      atypical antipsychotic therapy during gestation. Finally, published evidence
      about the effects on long-term infant neurodevelopment of drug exposure through
      both placenta and breast milk is represented only by sporadic case reports.
      CONCLUSIONS: It is well known that potential consequences of an untreated
      psychotic episode may be severe and may lead to the mother attempting suicide
      and/or infanticide. For these reasons, clinicians need to help mothers weigh both
      fetal and neonatal risks of exposure to drugs against the potential risk they and
      their infant may incur if the psychiatric illness is not treated. On the other
      hand, atypical antipsychotics in pregnancy and breast-feeding do not show evident
      advantages in safety when compared with typical neuroleptic agents. Therefore, we
      suggest that the most relevant parameters for selecting the best clinical option
      for pregnant and breast-feeding women with schizophrenia and related disorders
      remain strongly related to 3 main points: (1). cautious evaluation of the
      risk/benefit ratio of fetal and neonatal drug exposure, (2). degree of severity
      of maternal psychiatric illness, and (3). careful preliminary choice of drugs
      characterized by a balanced safety/efficacy profile.

PMID- 15150377
TI  - Bupropion for treatment of interferon-induced depression.
AB  - OBJECTIVE: To report the effect of bupropion in a patient with interferon (IFN)
      induced depression and review the use of antidepressants for treatment of
      depressive symptoms associated with IFN therapy. CASE SUMMARY: A 43-year-old
      white woman with chronic hepatitis C and severe IFN-induced depression was
      treated with sustained-release bupropion initiated at 150 mg/day for 7 days and
      100 mg twice daily thereafter. The dosage was increased again, to 350 mg/day when
      depressive symptoms recurred. While receiving that dose and continuing IFN
      treatment, she reported significant improvement in her depressive symptoms
      without experiencing any adverse effects. DISCUSSION: There is limited evidence
      suggesting that IFNs decrease central serotonergic transmission. There are
      several published reports on the use of selective serotonin-reuptake inhibitors
      for the treatment of IFN-induced depression. However, controlled studies are
      needed to assess the efficacy of serotonergic and noradrenergic antidepressants
      in IFN-treated patients with depressive symptoms. CONCLUSIONS: Sustained-release
      bupropion might be of potential benefit in patients with interferon-induced
      depression.

PMID- 15150378
TI  - Metformin for prevention of type 2 diabetes.
AB  - OBJECTIVE: To evaluate evidence from the medical literature that metformin is
      effective in preventing type 2 diabetes. DATA SOURCES: Primary literature was
      accessed via a MEDLINE search (1966-December 2003) using the terms metformin,
      type 2 diabetes, and prevention. DATA SYNTHESIS: Two studies evaluated
      metformin's potential to prevent type 2 diabetes, finding that metformin
      maintained or reduced fasting blood glucose in non-diabetics. Recently, a large
      study by the Diabetes Prevention Program showed that metformin may reduce the
      incidence of diabetes. Researchers compared lifestyle changes, metformin therapy,
      and placebo groups. They found that both lifestyle changes (58%) and metformin
      therapy (31%) significantly reduced the occurrence of type 2 diabetes versus
      placebo. CONCLUSIONS: These studies provide evidence that metformin may reduce
      the occurrence of type 2 diabetes. Because long-term efficacy has not been
      determined, further studies are needed.

PMID- 15150379
TI  - Impact of healthcare delivery system on where HMO-enrolled seniors purchase
      medications.

PMID- 15150380
TI  - Risk factors for community-acquired ciprofloxacin-resistant Escherichia coli
      urinary tract infection.
AB  - BACKGROUND: Fluoroquinolones are recommended for the empiric treatment of urinary
      tract infection (UTI) in communities in which uropathogen resistance to
      trimethoprim/sulfamethoxazole (TMP/SMX) is >or=10% to 20%. However, recent
      studies also have demonstrated an increase in the isolation of fluoroquinolone
      resistant Escherichia coli. Identification of outpatients at increased risk for
      fluoroquinolone resistance would improve the selection of empiric treatment.
      OBJECTIVE: To identify risk factors for community-acquired UTIs due to
      ciprofloxacin-resistant E. coli (CREC). METHODS: All medical records from the
      University of California at San Francisco Medical Center from January to December
      2001 were retrospectively reviewed to identify patients with community-acquired
      UTI due to CREC. Patients with community-acquired UTI due to ciprofloxacin
      susceptible E. coli presenting during the same time period were randomly selected
      as the study group in a 1:2 ratio of case to controls. RESULTS: Independent risk
      factors for CREC included recurrent UTI (OR 8.13) and prior exposure to
      fluoroquinolones (OR 30.35). CONCLUSIONS: Fluoroquinolones continue to be
      appropriate empiric treatment in most patients with uncomplicated UTI.
      Nitrofurantoin or a cephalosporin may be better choices in patients with
      recurrent lower UTI and/or previous fluoroquinolone use.

PMID- 15150381
TI  - SSRI treatment-associated stroke: causality assessment in two cases.
AB  - OBJECTIVE: To assess the probability of cerebrovascular adverse drug reactions
      (CV-ADRs) due to treatment with selective serotonin-reuptake inhibitors (SSRIs)
      using 2 causality methods. case summaries: Two patients with the possibility of
      SSRI-related stroke were referred for causality assessment. Causality assessment
      was performed using an adverse drug reaction probability scale, as well as
      clinical and radiologic parameters. A 31-year-old white man, who had been
      receiving paroxetine 200 mg/day over a period of 3 years, developed ischemic
      stroke involving left middle cerebral artery. The second patient was a 46-year
      old white woman with a history of recurrent depression who developed delirium and
      ischemic stroke while she was taking a combination of paroxetine 50 mg/day,
      trazodone 200 mg/day, and bupropion 150 mg/day. DISCUSSION: Carotid and
      cardiothromboembolism were found to be the major etiological factors for ischemic
      stroke. Accounting for the temporal relation, prior reports of SSRI treatment
      associated CV-ADRs, and the pharmacologic action of serotonin on coagulation and
      the vascular system, the possible contribution of SSRIs to stroke in these
      patients was considered. An objective causality assessment using the Naranjo
      probability scale revealed that a CV-ADR was possible. However, the nature of the
      stroke, plus clinical and radiologic findings, were inconsistent with known
      pathophysiologic mechanisms linking SSRIs and stroke in these patients.
      CONCLUSIONS: Causality assessment may improve unbiased recognition, management,
      and voluntary reporting of infrequent adverse effects such as SSRI treatment
      related cerebrovascular accident.

PMID- 15150382
TI  - An insulin infusion protocol in critically ill cardiothoracic surgery patients.
AB  - BACKGROUND: Critically ill cardiothoracic patients are prone to hyperglycemia and
      an increased risk of surgical site infections postoperatively. Aggressive insulin
      treatment is required to achieve tight glycemic control (TGC) and improve
      outcomes. OBJECTIVE: To examine and report on the performance of an insulin
      infusion protocol to maintain TGC, defined as a blood glucose level of 80-150
      mg/dL, in critically ill cardiothoracic surgical patients. METHODS: A nurse
      driven insulin infusion protocol was developed and initiated in postoperative
      cardiothoracic surgical intensive care patients with or without diabetes. In this
      before-after cohort study, 2 periods of measurement were performed: a 6-month
      baseline period prior to the initiation of the insulin infusion protocol (control
      group, n = 174) followed by a 6-month intervention period in which the protocol
      was used (TGC group, n = 168). RESULTS: Findings showed percent and time of blood
      glucose measurements within the TGC range (control 47% vs TGC 61%; p = 0.001),
      AUC of glucose exposure >150 mg/dL versus time for the first 24 hours of the
      insulin infusion (control 28.4 vs TGC 14.8; p < 0.001), median time to blood
      glucose <150 mg/dL (control 9.4 h vs TGC 2.1 h; p < 0.001), and percent blood
      glucose <65 mg/dL as a marker for hypoglycemia (control 9.8% vs TGC 16.7%; NS).
      CONCLUSIONS: An insulin infusion protocol designed to achieve a goal blood
      glucose range of 80-150 mg/dL efficiently and significantly improved TGC in
      critically ill postoperative cardiothoracic surgery patients without
      significantly increasing the incidence of hypoglycemia.

PMID- 15150383
TI  - Dyslipidemias and HMG-CoA reductase inhibitor prescription in heart transplant
      recipients.
AB  - BACKGROUND: The treatment of dyslipidemias in orthotopic heart transplant (OHT)
      recipients is not highlighted in the National Cholesterol Education Program Adult
      Treatment Panel guidelines. Emerging data suggest that hydroxymethylglutaryl
      coenzyme A reductase inhibitors (statins) safely reduce the risk of transplant
      rejection and coronary artery vasculopathy in OHT patients. OBJECTIVE: To assess
      the proportion of patients from our institution reaching the low-density
      lipoprotein cholesterol (LDL-C) target of <100 mg/dL, evaluate the impact of
      statins in reaching this goal, and evaluate the prescribing practice for statins
      in US OHT centers. METHODS: The management of dyslipidemia of OHT recipients
      followed at our institution was retrospectively evaluated. In addition, the use
      of statins in adult OHT centers in the US that performed >or=15 OHTs per year was
      assessed through a survey. RESULTS: Of the 328 patients from our institution,
      58.5% achieved an LDL-C <100 mg/dL. Patients prescribed statins were more likely
      to reach this goal (p < 0.01). A total of 85.0% of centers responding to the
      survey use statins as a part of their post-OHT protocol, primarily to reduce
      coronary artery vasculopathy (70.6%). CONCLUSIONS: Due to the potential for
      improved outcomes, a large proportion of patients are prescribed a statin. Our
      results support previous findings that statins are safe and effective in reducing
      LDL-C in the management of dyslipidemias in OHT recipients. Nonetheless,
      dyslipidemias are suboptimally managed in many post-OHT patients.

PMID- 15150385
TI  - Dust concentrations and respiratory risks in coalminers: key risk estimates from
      the British Pneumoconiosis Field Research.
AB  - To help inform the setting of dust control standards in coalmines, this brief
      review summarises the most recent and reliable exposure-response relations, for
      damaging respiratory effects, derived from the Pneumoconiosis Field Research
      (PFR). Collecting data over 38 years in the British coal industry, this was a
      programme of prospective research on the respiratory health of coal miners,
      characterised by regular health surveys and detailed measurements of dust and
      silica concentrations in the workplace. Exposure-response relations are presented
      for coal workers' simple pneumoconiosis category II, progressive massive
      fibrosis, defined deficits of lung function (FEV1), and category II silicosis.
      This simplified overview provides a guide to the most recent and most reliable
      estimates from the PFR of dust-related risks of substantial pulmonary disease,
      and to the magnitude of the effects. Control of dust sufficient to prevent
      category II simple pneumoconiosis should prevent most cases of progressive
      massive fibrosis and most dust related large lung function deficits. Where the
      dust contains high proportions of silica, control to low levels is essential, and
      even quite brief excursions of silica to high levels must be avoided.

PMID- 15150386
TI  - Twin frequency and industrial pollution in different regions of Hesse, Germany.
AB  - AIMS: To investigate whether twinning occurs more frequently in residents in the
      vicinity of a toxic waste incinerator (TWI). METHODS: Within a longitudinal
      environmental study that addressed child health second grade school children and
      their parents were recruited. The proportion of twinning in the TWI region was
      compared with two comparison areas. In a second confirmatory investigation, birth
      records for the years 1994-97 from the Hessian Perinatal Survey (HEPS) were
      accessed to determine whether the incidence of twinning was higher in regions
      around the TWI compared to adjacent reference areas. RESULTS: In the
      environmental study, 61.5% of the children and 95% of their mothers participated.
      In mothers, twinning was 5.3% in the TWI region compared to 1.6% and 2.3% in the
      comparison regions. The proportion of mothers with fertility assessment/treatment
      was 5.7%, 8.3%, and 0% respectively. The prevalence of twinning was not
      significantly higher (4.5%) in mothers with treatment compared to mothers without
      (3.7%). From the HEPS, data of 20 603 births was analysed. The incidence of twins
      was significantly higher in areas which surround the TWI and other industries
      (1.4-1.6 per 100 births) compared to births in reference areas (0.8 per 100).
      CONCLUSIONS: Twinning rates may be associated with exposure to industrial
      pollution. Future environmental health studies that consider multiple births as
      an outcome are warranted. These should also investigate whether the incidence of
      monozygotic or dizygotic twinning may be associated with industrial pollution.

PMID- 15150387
TI  - Professional and medical outcomes for French train drivers after "person under
      train" accidents: three year follow up study.
AB  - AIMS: To investigate psychiatric disorders, somatic health, and professional
      effects in French train drivers having experienced a "person under train"
      accident, and somatic health and professional effects. METHODS: A total of 202
      train drivers were evaluated several times: immediately after the event, three
      months later, and one, two, and three years later. These drivers were compared
      with 186 train drivers not exposed to that psychotraumatic shock. The evaluations
      relied primarily on the GHQ-28 and MINI questionnaires. RESULTS: In the exposed
      group, at the first evaluation, the prevalence of post-traumatic stress was 4%;
      scores > or =5 on the GHQ-28 were significantly higher than in the non-exposed
      group (32% versus 6%), for both the overall result and three sub-scores (somatic
      symptoms, anxiety and sleep, and psychosocial functioning). All these differences
      disappeared within a year. Vulnerability factors concerned prior traumas, acute
      and lasting life events, and the particular occupational situation where the
      driver is not accompanied but drives the train away alone in the aftermath of the
      accident. Over 95% of subjects had no short, medium, or long term impairment of
      their occupational fitness. CONCLUSIONS: Most of the psycho-behavioural disorders
      were observed in the immediate aftermath of the accident and disappeared within a
      year. The driver's occupational future does not seem to be affected by the
      "person under train" accident. Consideration of a traumatic accident as a job
      related risk and close psychological support of drivers after an accident
      probably increase the subject's ability to recover from the event.

PMID- 15150388
TI  - An epidemiological study of the magnitude and consequences of work related
      violence: the Minnesota Nurses' Study.
AB  - AIMS: To identify the magnitude of and potential risk factors for violence within
      a major occupational population. METHODS: Comprehensive surveys were sent to 6300
      Minnesota licensed registered (RNs) and practical (LPNs) nurses to collect data
      on physical and non-physical violence for the prior 12 months. Re-weighting
      enabled adjustment for potential biases associated with non-response, accounting
      for unknown eligibility. RESULTS: From the 78% responding, combined with non
      response rate information, respective adjusted rates per 100 persons per year
      (95% CI) for physical and non-physical violence were 13.2 (12.2 to 14.3) and 38.8
      (37.4 to 40.4); assault rates were increased, respectively, for LPNs versus RNs
      (16.4 and 12.0) and males versus females (19.4 and 12.9). Perpetrators of
      physical and non-physical events were patients/clients (97% and 67%,
      respectively). Consequences appeared greater for non-physical than physical
      violence. Multivariate modelling identified increased rates for both physical and
      non-physical violence for working: in a nursing home/long term care facility; in
      intensive care, psychiatric/behavioural or emergency departments; and with
      geriatric patients. CONCLUSIONS: Results show that non-fatal physical assault and
      non-physical forms of violence, and relevant consequences, are frequent among
      both RNs and LPNs; such violence is mostly perpetrated by patients or clients;
      and certain environmental factors appear to affect the risk of violence. This
      serves as the basis for further analytical studies that can enable the
      development of appropriate prevention and control efforts.

PMID- 15150389
TI  - Indices of asthma among atopic and non-atopic woodworkers.
AB  - AIMS: To investigate the relation between wood dust exposure and different
      indices of asthma among woodworkers and non-exposed subjects. METHODS: A total of
      302 woodworkers and 71 non-exposed subjects answered a respiratory health
      questionnaire, underwent a non-specific bronchial provocation test using the Yan
      method, and received a skin prick test with 12 common inhalant allergens.
      Subgroups performed repeated peak flow monitoring and underwent a reversibility
      test. A total of 347 dust measurements among 234 woodworkers were performed with
      passive dust monitors. RESULTS: The overall geometric mean (geometric standard
      deviation) exposure to inhalable dust was 0.96 (2.02) mg/m3. There was a tendency
      to increased risk of asthma among atopic woodworkers compared to atopic non
      exposed subjects, with ORs between 3.0 (0.8-11.9) (symptomatic BHR) and 1.3 (0.5
      4.2) (work related symptoms). In woodworkers, asthma was associated with atopy,
      with ORs between 7.4 (2.8-19.7) (symptomatic BHR) and 4.2 (2.4-7.7) (asthma
      symptoms). Asthma was related to dust level, most pronounced for symptomatic BHR
      among atopics, with OR 22.9 (1.0-523.6) for the highest compared to the lowest
      dust level. For work related asthma symptoms the association with dust level was
      seen only for non-atopics. CONCLUSIONS: Wood dust exposure was associated with
      asthma, despite a low dust level compared to other studies. Atopy was an
      important effect modifier in the association between asthma and wood dust
      exposure.

PMID- 15150391
TI  - Summer work and injury among middle school students, aged 10-14 years.
AB  - BACKGROUND: Little information exists on injury and factors associated with
      injury in working youth aged 10-14 years. Most studies do not involve children
      younger than 15. METHODS: A cross-sectional anonymous survey was administered to
      middle school students in five school districts and one large urban school in
      October 2001. RESULTS: Of the 3189 working middle school students who responded
      to the survey, the majority were employed in informal job settings, such as
      working for someone in a home, newspaper delivery, and working on family farms or
      in family businesses. Overall, 18% of children reported being injured at work. Of
      those injured, 26% reported that their injury was severe enough to affect their
      activities for more than three days. Variables that were associated with injury
      included having a "near-miss" incident at work (AOR 6.61, 95% CI 4.92 to 8.89),
      having a co-worker injured (AOR 2.65, 95% CI 1.95 to 3.60), and being asked to do
      something dangerous (AOR 2.25, 95% CI 1.61 to 3.14). CONCLUSIONS: Children are
      working and being injured in jobs that are not covered by existing child labour
      laws. Injury rates in non-covered occupations are high, warranting review of
      current laws.

PMID- 15150390
TI  - A descriptive study of work aggravated asthma.
AB  - BACKGROUND AND AIMS: Work related asthma (WRA) is one of the most frequently
      reported occupational lung diseases in a number of industrialised countries. A
      better understanding of work aggravated asthma (WAA), as well as work related new
      onset asthma (NOA), is needed to aid in prevention efforts. METHODS: WAA and NOA
      in the United States were compared using cases reported to the National Institute
      for Occupational Safety and Health (NIOSH) from four state Sentinel Event
      Notification Systems for Occupational Risks (SENSOR) surveillance programmes for
      1993-95. RESULTS: A total of 210 WAA cases and 891 NOA cases were reported. WAA
      cases reported mineral and inorganic dusts as the most common exposure agent, as
      opposed to NOA cases, in which diisocyanates were reported most frequently. A
      similar percentage of WAA and NOA cases still experienced breathing problems at
      the time of the interview or had visited a hospital or emergency room for work
      related breathing problems. NOA cases were twice as likely to have applied for
      workers' compensation compared with WAA cases. However, among those who had
      applied for worker compensation, approximately three-fourths of both WAA and NOA
      cases had received awards. The services and manufacturing industrial categories
      together accounted for the majority of both WAA (62%) and NOA (75%) cases. The
      risk of WAA, measured by average annual rate, was clearly the highest in the
      public administration (14.2 cases/10(5)) industrial category, while the risk of
      NOA was increased in both the manufacturing (3.2 cases/10(5)) and public
      administration (2.9 cases/10(5)) categories. CONCLUSIONS: WAA cases reported many
      of the same adverse consequences as NOA cases. Certain industries were identified
      as potential targets for prevention efforts based on either the number of cases
      or the risk of WAA and NOA.

PMID- 15150393
TI  - Mortality and cancer incidence among Lithuanian cement producing workers.
AB  - AIMS: To investigate mortality and cancer incidence of cement producing workers.
      METHODS: A total of 2498 cement workers who have been employed at Portland cement
      producing departments for at least one year from 1956 to 2000 were followed up
      from 1 January 1978 to 31 December 2000. The cohort contributed 43,490 person
      years to the study. Standardised incidence ratios (SIR) and standardised
      mortality ratios (SMR) were calculated as ratios between observed and expected
      numbers of cancers and deaths. The expected numbers were based on sex specific
      incidence and mortality rates for the total Lithuanian population. RESULTS:
      Significantly increased SMRs were found for all malignant neoplasms (SMR 1.3, 95%
      CI 1.0 to 1.5) and for lung cancer (SMR 1.4, 95% CI 1.0 to 1.9) among male cement
      workers. SIR for all cancer sites was 1.2 (95% CI 1.0 to 1.4). Excess risk was
      found for cancer of the lung (SIR 1.5, 95% CI 1.1 to 2.1). The SIR for urinary
      bladder cancer was also increased (SIR 1.8, 95% CI 0.9 to 3.5). The overall
      cancer incidence was not increased among females (SIR 0.8, 95% CI 0.6 to 1.1).
      With increasing cumulated exposure to cement dust, there were indications of an
      increasing risk of lung and stomach cancers among males. CONCLUSIONS: This study
      supported the hypothesis that exposure to cement dust may increase the lung and
      bladder cancer risk. A dose related risk was found for stomach cancer, but no
      support was found for an increased risk of colorectal cancer.

PMID- 15150394
TI  - Evaluation of the mercury exposure of dental amalgam patients by the Mercury
      Triple Test.
AB  - AIMS: To establish and analyse reference data for the mercury burden of patients
      with and without amalgam fillings. METHODS: Atomic absorption spectroscopy was
      used to quantify Hg concentrations in the scalp hair and urine (before and after
      application of dimercaptopropane sulphonate), and Hg release from dental amalgams
      (using a newly developed, amalgam specific chew test), in 2223 subjects. RESULTS:
      50th centiles were 1.3 microg Hg/g creatinine in basal urine, 32 microg Hg/g
      creatinine after DMPS application, 454 ng Hg/g in hair, and 27 microg Hg per g of
      chewing gum, which corresponds to about 1 micro g Hg released per minute of
      chewing. Total Hg intake (from ambient air, drinking water, food, and amalgams)
      of most patients is well below the provisioned tolerable weekly intake (PTWI)
      defined by the WHO, unless extremely Hg rich food is consumed on a regular basis.
      However, for patients exceeding the 75th centile in chew tests, total Hg intake
      exceeds the PTWI by about 50%, even at the low limit of intake from food. In the
      absence of occupational exposure, significant Hg release from dental amalgams is
      a necessary but insufficient condition to obtain a high long term body burden.
      After removal of dental amalgams, chew tests no longer exhibit oral Hg exposure,
      while basal urine Hg content and DMPS induced excretion display a exponential
      decrease (half life about 2 months in both cases). CONCLUSIONS: A standardised
      procedure for evaluation of the magnitude and origin of the Hg burden of
      individuals has been developed, which, by comparison with the database presented
      here for the first time, can serve as a diagnostic tool.

PMID- 15150392
TI  - Perceived muscular tension, job strain, physical exposure, and associations with
      neck pain among VDU users; a prospective cohort study.
AB  - AIMS: To determine whether perceived muscular tension, job strain, or physical
      exposure are associated with increased risk of developing neck pain among VDU
      users. METHODS: A baseline questionnaire was answered by 1283 respondents, of
      whom 671 were free from neck pain at baseline. Perceived muscular tension, job
      strain, and physical exposure were assessed at baseline. Information about newly
      developed neck pain was collected in 10 follow up questionnaires and the case
      definition was the first report of such pain in any of the follow up
      questionnaires. Median follow up time was 10.9 months. RESULTS: Both men and
      women who perceived muscular tension at least a few times per week, compared to
      those who had not perceived muscular tension the preceding month, had an
      incidence rate ratio (IRR) of 1.9 (95% CI 1.25 to 2.93) for developing neck pain,
      when stratifying for sex. High perceived muscular tension was associated with an
      increased risk (IRR 1.6, 95% CI 1.02 to 1.91), even when controlling for job
      strain, physical exposure, and age in the model stratified by sex. CONCLUSIONS:
      Perceived muscular tension was associated with an increased risk of developing
      neck pain among VDU users. The combination of high job strain and high perceived
      muscular tension was associated with higher risk of developing neck pain than the
      combination of high physical exposure and high perceived muscular tension. There
      was an indication of an excess risk due to interaction between high physical
      exposure and high job strain.

PMID- 15150395
TI  - Mortality and cancer incidence in New Zealand meat workers.
AB  - AIMS: To ascertain whether there is an increased risk of cancers of the lung and
      lymphohaematopoietic tissue in workers employed in the New Zealand meat
      processing industry, and to identify exposures associated with any increased
      risks. METHODS: A cohort of 6647 individuals assembled from personnel records
      from three plants was followed from 1988 until 2000. The observed number of
      deaths and cancer registrations was compared with expected numbers using five
      year age and gender specific rates for the New Zealand population. Subgroup
      analyses evaluated the effect of duration of exposure to selected agents, based
      on job titles and departments. RESULTS: Vital status was determined for 84% of
      the cohort, and 92% of the total possible person-years. Mortality from all causes
      and all cancers was increased, and there was a significant excess of lung cancer.
      There were significant trends of increasing risk of lung and lymphohaematopoietic
      cancer with increasing duration of exposure to biological material. CONCLUSIONS:
      Excess risks were observed for mortality from all causes, all cancers, and lung
      cancer. Although the increased risk of lung cancer may be partly due to
      confounding by smoking, it is unlikely to be entirely due to this cause.
      Furthermore, the dose-response relation observed for lung cancer suggests the
      effect is related to exposure to biological material contained in animal urine,
      faeces, and blood. Although numbers were small, the risk of lymphohaematopoietic
      cancer was also associated with increasing duration and level of exposure to
      biological material.

PMID- 15150396
TI  - Enhanced oxidative stress in workers with a standing occupation.
AB  - BACKGROUND: Several epidemiological studies have shown a statistically
      significant association between standing work and chronic venous insufficiency of
      lower limbs. This condition has been associated with an enhanced oxidative stress
      that, according to the literature, could represent a risk factor for
      cardiovascular and other systemic diseases. AIMS AND METHODS: To evaluate venous
      pressure of the lower limbs and reactive oxygen species (ROS) before and after
      work in 62 workers with a standing occupation (surgery room nurses) and 65
      outpatient department nurses who can walk during their working time. RESULTS:
      After work, a statistically significant increase of venous pressure of the lower
      limbs levels was observed in both the study group and controls. Standing workers
      showed significantly higher mean levels of ROS after work.

PMID- 15150397
TI  - Exposure-response relations for work related respiratory symptoms and
      sensitisation in a cohort exposed to alpha-amylase.
AB  - AIMS: To explore relations between exposure to fungal alpha-amylase and the risk
      of new work related respiratory symptoms or sensitisation. METHODS: A prospective
      cohort study among 300 bakers and millers was followed up for a maximum of seven
      years. Exposure to alpha-amylase was estimated by air measurements and
      questionnaires and classified into three categories. Symptoms were recorded with
      a self-administered questionnaire and skin sensitisation assessed using skin
      prick test (SPT). RESULTS: There were 36 new cases of chest symptoms, 86 of
      eyes/nose symptoms, and 24 of a positive SPT to alpha-amylase. There were
      exposure-response relations for chest and eyes/nose symptoms and for
      sensitisation, and a significantly increased prevalence ratio for chest symptoms
      in the highest exposure category. CONCLUSION: A reduction in alpha-amylase
      exposure is likely to reduce the risk for respiratory morbidity in bakery
      workers.

PMID- 15150399
TI  - World at work: soldiering.

PMID- 15150400
TI  - The evidence for workplace counselling is in Medline.

PMID- 15150401
TI  - Occupational exposure of midwives to nitrous oxide on delivery suites.

PMID- 15150402
TI  - Comments on article by Koh and Aw.

PMID- 15150403
TI  - Mobile phone use and cancer.

PMID- 15150404
TI  - The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation
      dependent c-Myc protein degradation.
AB  - Myc proteins regulate cell growth and division and are implicated in a wide range
      of human cancers. We show here that Fbw7, a component of the SCF(Fbw7) ubiquitin
      ligase and a tumor suppressor, promotes proteasome-dependent c-Myc turnover in
      vivo and c-Myc ubiquitination in vitro. Phosphorylation of c-Myc on threonine-58
      (T58) by glycogen synthase kinase 3 regulates the binding of Fbw7 to c-Myc as
      well as Fbw7-mediated c-Myc degradation and ubiquitination. T58 is the most
      frequent site of c-myc mutations in lymphoma cells, and our findings suggest that
      c-Myc activation is one of the key oncogenic consequences of Fbw7 loss in cancer.
      Because Fbw7 mediates the degradation of cyclin E, Notch, and c-Jun, as well as c
      Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation
      during tumorigenesis.

PMID- 15150405
TI  - Trafficking of ODV-E66 is mediated via a sorting motif and other viral proteins:
      facilitated trafficking to the inner nuclear membrane.
AB  - The N-terminal 33 aa of the envelope protein ODV-E66 are sufficient to traffic
      fusion proteins to intranuclear membranes and the ODV envelope during infection
      with Autographa californica nucleopolyhedrovirus. This sequence has two distinct
      features: (i) an extremely hydrophobic sequence of 18 aa and (ii) positively
      charged amino acids close to the C-terminal end of the hydrophobic sequence. In
      the absence of infection, this sequence is sufficient to promote protein
      accumulation at the inner nuclear membrane. Covalent cross-linking results show
      that the lysines of the motif are proximal to FP25K and/or BV/ODV-E26 during
      transit from the endoplasmic reticulum to the nuclear envelope. We propose that
      the 33 aa comprise a signature for sorting proteins to the inner nuclear membrane
      (sorting motif) and that, unlike other resident proteins of the inner nuclear
      membrane, ODV-E66 and sortingmotif fusions do not randomly diffuse from their
      site of insertion at the endoplasmic reticulum to the nuclear envelope and viral
      induced intranuclear membranes. Rather, during infection, trafficking is mediated
      by protein-protein interactions.

PMID- 15150406
TI  - Phi-value analysis and the nature of protein-folding transition states.
AB  - Phi values are used to map structures of protein-folding transition states from
      changes in free energies of denaturation (DeltaDeltaG(D-N)) and activation on
      mutation. A recent reappraisal proposed that Phi values for DeltaDeltaG(D-N) <
      1.7 kcal/mol are artifactual. On discarding such derived Phi values from
      published studies, the authors concluded that there are no high Phi values in
      diffuse transition states, which are consequently uniformly diffuse with no
      evidence for nucleation. However, values of DeltaDeltaG(D-N) > 1.7 kcal/mol are
      often found for large side chains that make dispersed tertiary interactions,
      especially in hydrophobic cores that are in the process of being formed in the
      transition state. Conversely, specific local interactions that probe secondary
      structure tend to have DeltaDeltaG(D-N) approximately 0.5-2 kcal/mol. Discarding
      Phi values from lower-energy changes discards the crucial information about local
      interactions and makes transition states appear uniformly diffuse by
      overemphasizing the dispersed tertiary interactions. The evidence for the 1.7
      kcal/mol cutoff was based on mutations that had been deliberately designed to be
      unsuitable for Phi-value analysis because they are structurally disruptive. We
      confirm that reliable Phi values can be derived from the recommended mutations in
      suitable proteins with 0.6 < DeltaDeltaG(D-N) < 1.7 kcal/mol, and there are many
      reliable high Phi values. Transition states vary from being rather diffuse to
      being well formed with islands of near-complete secondary structure. We also
      confirm that the structures of transition-state ensembles can be perturbed by
      mutations with DeltaDeltaG(D-N) >> 2 kcal/mol and that protein-folding transition
      states do move on the energy surface on mutation.

PMID- 15150407
TI  - Hippocampal long-term depression and long-term potentiation encode different
      aspects of novelty acquisition.
AB  - The hippocampus is required for encoding spatial information. Little is known
      however, about how different attributes of learning are related to different
      types of synaptic plasticity. Here, we investigated the association between long
      term depression (LTD) and long-term potentiation, both cellular models for
      learning, and novelty exploration. We found that exploration of a new environment
      containing unfamiliar objects and/or familiar objects in new locations
      facilitated LTD, whereas exploration of the new environment itself, in the
      absence of objects, impaired LTD. Furthermore, we found this phenomenon to be
      modulated by 5-hydroxytryptamine 4 receptor activation. In contrast, long-term
      potentiation was facilitated by exploration of an empty novel environment, but
      simultaneous object exploration caused depotentiation. We also found that no
      further LTD could be induced. These findings support a decisive role for LTD in
      the acquisition of object-place configuration and consolidate its candidacy as a
      learning mechanism.

PMID- 15150409
TI  - Structural basis for recognition of the AGNN tetraloop RNA fold by the double
      stranded RNA-binding domain of Rnt1p RNase III.
AB  - Specific recognition of double-stranded RNA (dsRNA) by dsRNA-binding domains
      (dsRBDs) is involved in a large number of biological and regulatory processes.
      Although structures of dsRBDs in complex with dsRNA have revealed how they can
      bind to dsRNA in general, these do not explain how a dsRBD can recognize specific
      RNAs. Rnt1p, a member of the RNase III family of dsRNA endonucleases, is a key
      component of the Saccharomyces cerevisiae RNA-processing machinery. The Rnt1p
      dsRBD has been implicated in targeting this endonuclease to its RNA substrates,
      by recognizing hairpins closed by AGNN tetraloops. We report the solution
      structure of Rnt1p dsRBD complexed to the 5' terminal hairpin of one of its small
      nucleolar RNA substrates, the snR47 precursor. The conserved AGNN tetraloop fold
      is retained in the protein-RNA complex. The dsRBD contacts the RNA at successive
      minor, major, and tetraloop minor grooves on one face of the helix. Surprisingly,
      neither the universally conserved G nor the highly conserved A are recognized by
      specific hydrogen bonds to the bases. Rather, the N-terminal helix fits snugly
      into the minor groove of the RNA tetraloop and top of the stem, interacting in a
      non-sequence-specific manner with the sugar-phosphate backbone and the two
      nonconserved tetraloop bases. Mutational analysis of residues that contact the
      tetraloop region show that they are functionally important for RNA processing in
      the context of the entire protein in vivo. These results show how a single dsRBD
      can convey specificity for particular RNA targets, by structure specific
      recognition of a conserved tetraloop fold.

PMID- 15150408
TI  - A balance between the diap1 death inhibitor and reaper and hid death inducers
      controls steroid-triggered cell death in Drosophila.
AB  - The steroid hormone ecdysone directs the massive destruction of obsolete larval
      tissues during Drosophila metamorphosis, providing a model system for defining
      the molecular mechanisms of steroid-regulated programmed cell death. Although
      earlier studies have identified an ecdysone triggered genetic cascade that
      immediately precedes larval tissue cell death, no death regulatory genes have
      been functionally linked to this death response. We show here that ecdysone
      induced expression of the death activator genes reaper (rpr) and head involution
      defective (hid) is required for destruction of the larval midgut and salivary
      glands during metamorphosis, with hid playing a primary role in the salivary
      glands and rpr and hid acting in a redundant manner in the midguts. We also
      identify the Drosophila inhibitor of apoptosis 1 as a survival factor in the
      larval cell death pathway, delaying death until its inhibitory effect is overcome
      by rpr and hid. This study reveals functional interactions between rpr and hid in
      Drosophila cell death responses and provides evidence that the precise timing of
      larval tissue cell death during metamorphosis is achieved through a steroid
      triggered shift in the balance between the Drosophila inhibitor of apoptosis 1
      and the rpr and hid death activators.

PMID- 15150410
TI  - Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional
      exchange characteristics of the mouse placenta.
AB  - Restricted fetal growth is associated with postnatal mortality and morbidity and
      may be directly related to alterations in the capacity of the placenta to supply
      nutrients. We proposed previously that imprinted genes can regulate nutrient
      supply by the placenta. Here, we tested the hypothesis that the insulin-like
      growth factor 2 gene (Igf2) transcribed from the placental-specific promoter (P0)
      regulates the development of the diffusional permeability properties of the mouse
      placenta. Using mice in which placental-specific Igf2 had been deleted (P0), we
      measured the transfer in vivo of three inert hydrophilic solutes of increasing
      size (14C-mannitol, 51CrEDTA, and 14C-inulin). At embryonic day 19, placental and
      fetal weights in P0 conceptuses were reduced to 66% and 76%, respectively, of
      wild type. In P0 mutants, the permeability.surface area product for the tracers
      at this stage of development was 68% of that of controls; this effect was
      independent of tracer size. Stereological analysis of histological sections
      revealed the surface area of the exchange barrier in the labyrinth of the mouse
      placenta to be reduced and thickness increased in P0 fetuses compared to wild
      type. As a result, the average theoretical diffusing capacity in P0 knockout
      placentas was dramatically reduced to 40% of that of wild-type placentas. These
      data show that placental Igf2 regulates the development of the diffusional
      exchange characteristics of the mouse placenta. This provides a mechanism for the
      role of imprinted genes in controlling placental nutrient supply and fetal
      growth. Altered placental Igf2 could be a cause of idiopathic intrauterine growth
      restriction in the human.

PMID- 15150411
TI  - Dynamers: polyacylhydrazone reversible covalent polymers, component exchange, and
      constitutional diversity.
AB  - Component exchange in reversible polymers allows the generation of dynamic
      constitutional diversity. The polycondensation of dihydrazides with dialdehydes
      generates polyacylhydrazones, to which the acylhydrazone functionality formed
      confers both hydrogen-bonding and reversibility features through the amide and
      imine groups, respectively. Polyacylhydrazones are thus dynamic polyamides. They
      are able to reversibly exchange either one or both of their repeating monomer
      units in the presence of different monomers, thus presenting constitutional
      dynamic diversity. The polymers subjected to monomer exchange/interchange may be
      brought to exhibit physical properties vastly different from those of the
      original polymer. The principle may be extended to other important classes of
      polymers, giving access, for instance, to dynamic polyureas or polycarbamates.
      These reversible polymers are therefore able to incorporate, decorporate, or
      reshuffle their constituting monomers, namely in response to environmental
      physical or chemical factors, an adaptability feature central to constitutional
      dynamic chemistry.

PMID- 15150413
TI  - Simulation, experiment, and evolution: understanding nucleation in protein S6
      folding.
AB  - In this study, we explore nucleation and the transition state ensemble of the
      ribosomal protein S6 using a Monte Carlo (MC) Go model in conjunction with
      restraints from experiment. The results are analyzed in the context of extensive
      experimental and evolutionary data. The roles of individual residues in the
      folding nucleus are identified, and the order of events in the S6 folding
      mechanism is explored in detail. Interpretation of our results agrees with, and
      extends the utility of, experiments that shift phi-values by modulating
      denaturant concentration and presents strong evidence for the realism of the
      mechanistic details in our MC Go model and the structural interpretation of
      experimental phi-values. We also observe plasticity in the contacts of the
      hydrophobic core that support the specific nucleus. For S6, which binds to RNA
      and protein after folding, this plasticity may result from the conformational
      flexibility required to achieve biological function. These results present a
      theoretical and conceptual picture that is relevant in understanding the
      mechanism of nucleation in protein folding.

PMID- 15150414
TI  - Coral decline threatens fish biodiversity in marine reserves.
AB  - The worldwide decline in coral cover has serious implications for the health of
      coral reefs. But what is the future of reef fish assemblages? Marine reserves can
      protect fish from exploitation, but do they protect fish biodiversity in
      degrading environments? The answer appears to be no, as indicated by our 8-year
      study in Papua New Guinea. A devastating decline in coral cover caused a parallel
      decline in fish biodiversity, both in marine reserves and in areas open to
      fishing. Over 75% of reef fish species declined in abundance, and 50% declined to
      less than half of their original numbers. The greater the dependence species have
      on living coral as juvenile recruitment sites, the greater the observed decline
      in abundance. Several rare coral-specialists became locally extinct. We suggest
      that fish biodiversity is threatened wherever permanent reef degradation occurs
      and warn that marine reserves will not always be sufficient to ensure their
      survival.

PMID- 15150412
TI  - A steroid modulatory domain on NR2B controls N-methyl-D-aspartate receptor proton
      sensitivity.
AB  - N-methyl-D-aspartate (NMDA) receptor function is modulated by several endogenous
      molecules, including zinc, polyamines, protons, and sulfated neurosteroids. Zinc,
      polyamines, and phenylethanolamines exert their respective modulatory effects by
      exacerbating or relieving tonic proton inhibition. Here, we report that
      pregnenolone sulfate (PS) uses a unique mechanism for enhancement of NMDA
      receptor function that is independent of the proton sensor. We identify a steroid
      modulatory domain, SMD1, on the NMDA receptor NR2B subunit that is critical for
      both PS enhancement and proton sensitivity. This domain includes the J/K helices
      in the S2 region of the glutamate recognition site and the fourth membrane
      transmembrane region (M4). A molecular model based on alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor structure suggests that steroid
      modulatory domain 1 contributes residues to a hydrophobic pocket that is capable
      of accommodating PS. The results demonstrate that the J/K helices and the fourth
      membrane transmembrane region participate in transducing allosteric interactions
      induced by steroid and proton binding to their respective sites.

PMID- 15150415
TI  - Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)
      dependent Sir2 histone/protein deacetylases.
AB  - Sir2 enzymes are broadly conserved from bacteria to humans and have been
      implicated to play roles in gene silencing, DNA repair, genome stability,
      longevity, metabolism, and cell physiology. These enzymes bind NAD(+) and
      acetyllysine within protein targets and generate lysine, 2'-O-acetyl-ADP-ribose,
      and nicotinamide products. To provide structural insights into the chemistry
      catalyzed by Sir2 proteins we report the high-resolution ternary structure of
      yeast Hst2 (homologue of Sir two 2) with an acetyllysine histone H4 peptide and a
      nonhydrolyzable NAD(+) analogue, carba-NAD(+), as well as an analogous ternary
      complex with a reaction intermediate analog formed immediately after nicotinamide
      hydrolysis, ADP-ribose. The ternary complex with carba-NAD(+) reveals that the
      nicotinamide group makes stabilizing interactions within a binding pocket
      harboring conserved Sir2 residues. Moreover, an asparagine residue, N116,
      strictly conserved within Sir2 proteins and shown to be essential for
      nicotinamide exchange, is in position to stabilize the oxocarbenium intermediate
      that has been proposed to proceed the hydrolysis of nicotinamide. A comparison of
      this structure with the ADP-ribose ternary complex and a previously reported
      ternary complex with the 2'-O-acetyl-ADP-ribose reaction product reveals that the
      ribose ring of the cofactor and the highly conserved beta1-alpha2 loop of the
      protein undergo significant structural rearrangements to facilitate the ordered
      NAD(+) reactions of nicotinamide cleavage and ADP-ribose transfer to acetate.
      Together, these studies provide insights into the chemistry of NAD(+) cleavage
      and acetylation by Sir2 proteins and have implications for the design of Sir2
      specific regulatory molecules.

PMID- 15150416
TI  - Completion of neuronal migration regulated by loss of Ca(2+) transients.
AB  - The migration of immature neurons constitutes one of the major processes by which
      the central nervous system takes shape. Completing the migration at the final
      destination requires the loss of cell body motility, but little is known about
      the signaling mechanisms underlying this process. Here, we show that a loss of
      transient Ca(2+) elevations triggers the completion of cerebellar granule cell
      migration. Simultaneous observation of the intracellular Ca(2+) levels and cell
      movement in cerebellar slices of the early postnatal mice revealed that granule
      cells exhibit distinct frequencies of the transient Ca(2+) elevations as they
      migrate in different cortical layers, and complete the migration only after the
      loss of Ca(2+) elevations. The reduction of the Ca(2+) elevation frequency by
      decreasing Ca(2+) influx, or by inhibiting the activity of phospholipase C, PKC,
      or Ca(2+)/calmodulin, halted the granule cell movement prematurely. In contrast,
      increasing the Ca(2+) elevation frequency by increasing Ca(2+) release from
      internal stores, or by elevating intracellular cAMP levels, significantly delayed
      the completion of granule cell migration. The timing of the loss of Ca(2+)
      elevations was intrinsically set in the granule cells and influenced by external
      cues. These results suggest that Ca(2+) signaling, dictated by multiple signaling
      systems, functions as a mediator for completing the migration of immature
      neurons.

PMID- 15150417
TI  - Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition
      using spike protein heptad repeat-derived peptides.
AB  - The coronavirus SARS-CoV is the primary cause of the life-threatening severe
      acute respiratory syndrome (SARS). With the aim of developing therapeutic agents,
      we have tested peptides derived from the membrane-proximal (HR2) and membrane
      distal (HR1) heptad repeat region of the spike protein as inhibitors of SARS-CoV
      infection of Vero cells. It appeared that HR2 peptides, but not HR1 peptides,
      were inhibitory. Their efficacy was, however, significantly lower than that of
      corresponding HR2 peptides of the murine coronavirus mouse hepatitis virus (MHV)
      in inhibiting MHV infection. Biochemical and electron microscopical analyses
      showed that, when mixed, SARS-CoV HR1 and HR2 peptides assemble into a six-helix
      bundle consisting of HR1 as a central triple-stranded coiled coil in association
      with three HR2 alpha-helices oriented in an antiparallel manner. The stability of
      this complex, as measured by its resistance to heat dissociation, appeared to be
      much lower than that of the corresponding MHV complex, which may explain the
      different inhibitory potencies of the HR2 peptides. Analogous to other class I
      viral fusion proteins, the six-helix complex supposedly represents a postfusion
      conformation that is formed after insertion of the fusion peptide, proposed here
      for coronaviruses to be located immediately upstream of HR1, into the target
      membrane. The resulting close apposition of fusion peptide and spike
      transmembrane domain facilitates membrane fusion. The inhibitory potency of the
      SARS-CoV HR2-peptides provides an attractive basis for the development of a
      therapeutic drug for SARS.

PMID- 15150418
TI  - Global analysis of predicted proteomes: functional adaptation of physical
      properties.
AB  - The physical characteristics of proteins are fundamentally important in
      organismal function. We used the complete predicted proteomes of >100 organisms
      spanning the three domains of life to investigate the comparative biology and
      evolution of proteomes. Theoretical 2D gels were constructed with axes of protein
      mass and charge (pI) and converted to density estimates comparable across all
      types and sizes of proteome. We asked whether we could detect general patterns of
      proteome conservation and variation. The overall pattern of theoretical 2D gels
      was strongly conserved across all life forms. Nevertheless, coevolved replicons
      from the same organism (different chromosomes or plasmid and host chromosomes)
      encode proteomes more similar to each other than those from different organisms.
      Furthermore, there was disparity between the membrane and nonmembrane
      subproteomes within organisms (proteins of membrane proteomes are on the average
      more basic and heavier) and their variation across organisms, suggesting that
      membrane proteomes evolve most rapidly. Experimentally, a significant positive
      relationship independent of phylogeny was found between the predicted proteome
      and Biolog profile, a measure associated with the ecological niche. Finally, we
      show that, for the smallest and most alkaline proteomes, there is a negative
      relationship between proteome size and basicity. This relationship is not
      adequately explained by AT bias at the DNA sequence level. Together, these data
      provide evidence of functional adaptation in the properties of complete
      proteomes.

PMID- 15150421
TI  - During the respiratory burst, do phagocytes need proton channels or potassium
      channels, or both?
AB  - The NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase
      enzyme complex, a crucial component of innate immunity, produces superoxide anion
      (O2-), which is a precursor to many reactive oxygen species. NADPH oxidase
      produces O2- by transferring electrons from intracellular NADPH across the
      membrane to extracellular (or phagosomal) oxygen and is thus electrogenic. It is
      widely believed that electroneutrality is preserved by proton flux through
      voltage-gated proton channels. A series of recent papers have challenged several
      key aspects of this view of the "respiratory burst." The most recent study
      solidifies the proposal that O2- and other reactive oxygen species produced by
      phagocytes are not toxic to microbes under physiological conditions. Further, an
      essential role for high-conductance, Ca2+-activated K+ (maxi-K+) channels in
      microbe killing is proposed. Finally, the results cast doubt on the widely held
      view that H+ efflux through voltage-gated proton channels (i) is the main
      mechanism of charge compensation, and (ii) is essential to continuous O2-
      production by the NADPH oxidase. My analysis of the new data and of a large body
      of data in the literature indicates that the proposed role of maxi-K+ channels in
      the respiratory burst is not yet credibly established. H+ efflux through proton
      channels thus remains the most viable mechanism for charge compensation and
      continuous O2- production. The important question of the toxicity of reactive
      oxygen species in phagocytes and in other cells, which has long been simply taken
      for granted, is a widespread assumption that deserves critical study.

PMID- 15150419
TI  - The evolution of a pleiotropic fitness tradeoff in Pseudomonas fluorescens.
AB  - The evolution of ecological specialization is expected to carry a cost, due to
      either antagonistic pleiotropy or mutation accumulation. In general, it has been
      difficult to distinguish between these two possibilities. Here, we demonstrate
      that the experimental evolution of niche-specialist genotypes of the bacterium
      Pseudomonas fluorescens that colonize the air-broth interface of spatially
      structured microcosms is accompanied by pleiotropic fitness costs in terms of
      reduced carbon catabolism. Prolonged selection in spatially structured microcosms
      caused the cost of specialization to decline without loss of the benefits
      associated with specialization. The decline in the cost of specialization can be
      explained by either compensatory adaptation within specialist lineages or clonal
      competition among specialist lineages. These results provide a possible
      explanation of conflicting accounts for the cost of specialization.

PMID- 15150422
TI  - Metabolic modulation of potassium channels.
AB  - Recent investigations have shown that a range of small molecules that reflect the
      metabolic state of a cell regulate the activity of potassium channels. For
      instance, hydrogen peroxide has been shown to activate adenosine 5'-triphosphate
      sensitive potassium channels (K(ATP) channels), whereas heme closes certain
      calcium-activated potassium channels. Although the exact function of the beta
      subunit associated with voltage-gated potassium channels is still unclear, its
      crystal structure suggests that membrane excitability is directly coupled to
      metabolism.

PMID- 15150423
TI  - TRPM7: channeling the future of cellular magnesium homeostasis?
AB  - A recent paper by Schmitz and colleagues provides persuasive evidence that the
      ion channel transient receptor potential melastatin 7 (TRPM7) may be the long
      sought regulator of magnesium (Mg) homeostasis in mammalian cells. This finding
      is not unexpected, because TRPM channels contain a kinase domain that allows them
      to participate in signal transduction pathways and regulatory networks. However,
      these studies introduce an exciting new twist into our understanding of Mg
      homeostasis; TRPM7 facilitates Mg entry into the cell, whereas other putative Mg
      transporters apparently operate in the opposite direction. By combining
      electrophysiological, biochemical, and genetic approaches, Schmitz and colleagues
      characterized most of the key features that demonstrate a well-defined and
      biologically plausible regulator of Mg homeostasis. TRPM7 genetics are well in
      hand, its regulation by intracellular free Mg2+ unravels the mechanisms of
      regulatory feedback loops, and its kinase domain modulates its sensitivity to
      free Mg2+. These findings are discussed in light of the indirect and descriptive
      information we had about Mg regulation before this rigorous characterization of
      TRPM7 brought it to the center of the Mg stage. Although the molecular events
      downstream of TRPM7 phosphorylation and dephosphorylation await in-depth
      elucidation, these results open up exciting perspectives in Mg research and may
      provide a much-needed tool with which to reexamine the role of Mg in cell
      proliferation and other important pathophysiologic events. Likewise, these
      findings will offer guidelines for research on disease states that are
      characterized by Mg imbalance.

PMID- 15150424
TI  - Intracellular chloride channels: determinants of function in the endosomal
      pathway.
AB  - Endosomes, and related subcellular compartments, contain various Cl- channels in
      the ClC family. In this review, we describe the known roles of intracellular Cl-
      channels and also explore some of the functional implications of transmembrane Cl
      flux in these organelles. Cl- influx acts to control intralumenal pH, both by
      shunting the effects of the proton pump on membrane potential and, possibly,
      through direct effects of Cl- on the proton pump. Changes in intralumenal pH
      likely help regulate membrane trafficking. We propose that changes in
      intralumenal Cl- concentration ([Cl-]) could theoretically play a direct role in
      regulating membrane trafficking and organellar function through effects on
      chloride-sensitive proteins in the vesicular membrane, which could transduce
      information about intralumenal [Cl-] to the outside of the vesicle and thereby
      recruit various signaling molecules. We present a model in which regulation of
      cytosolic [Cl-] and vesicular Cl- conductance could help control the amount or
      type of neurotransmitter stored in a particular population of synaptic vesicles.

PMID- 15150426
TI  - The role of interleukin-1 in the pathogenesis of rheumatoid arthritis.
AB  - A significant body of experimental evidence has implicated the proinflammatory
      cytokine IL-1 in the pathogenesis of RA. For example, IL-1beta overexpression in
      rabbit knee joints causes arthritis with clinical and histological features
      characteristic of RA, whereas IL-1 deficiency is associated with reduced joint
      damage. In experimental models, IL-1 blockers, including IL-1 receptor antagonist
      (IL-1Ra), significantly reduce clinical and histological disease parameters. In
      RA patients, plasma and synovial fluid concentrations of IL-1 are elevated, and
      these correlate with various parameters of disease activity. The production of
      endogenous IL-1Ra, however, appears to be insufficient to balance these higher IL
      1 levels. The efficacy of blocking IL-1 in patients with active RA has been
      established in controlled clinical trials of anakinra, a recombinant human IL-1Ra
      (r-metHuIL-1ra). When used alone or in combination with methotrexate, anakinra
      significantly reduces the clinical signs and symptoms of RA compared with
      placebo. Taken together, these results indicate that IL-1 plays an important role
      in the pathogenesis of RA.

PMID- 15150427
TI  - The role of interleukin-1 in bone resorption in rheumatoid arthritis.
AB  - Bone loss in RA includes juxta-articular osteopenia, erosions and systemic
      osteoporosis. In each case, synthesis of new bone matrix is unable to balance
      osteoclast-mediated bone resorption, resulting in net bone loss. IL-1, TNF and
      other proinflammatory cytokines stimulate osteoclast differentiation and
      activation, resulting in bone loss. In addition, these proinflammatory cytokines
      stimulate synovial fibroblasts and chondrocytes to produce proteinases that
      degrade cartilage. In animal arthritis models, blocking IL-1 significantly
      reduces bone erosions and cartilage degradation, whereas blocking TNF decreases
      synovitis. In patients with active RA, treatment with the TNF blockers etanercept
      and infliximab, as well as with anakinra, a recombinant human IL-1 receptor
      antagonist, significantly reduced erosions and joint space narrowing. It remains
      to be determined, however, whether slowing radiographic progression with these
      biological therapies will significantly improve long-term outcomes in RA.

PMID- 15150428
TI  - The impact of new biologicals in the treatment of rheumatoid arthritis.
AB  - The past decade has seen a shift in the paradigm for RA management. DMARDs have
      been introduced at earlier stages of disease in an effort to slow or stop
      radiographic disease progression before irreversible joint damage, work
      disability, functional decline and other adverse outcomes are seen. Although
      often effective, DMARDs have been limited in treatment durability over the long
      term due to side-effects and declining efficacy. Combination regimens, often
      involving weekly methotrexate as the anchor drug, have been used increasingly to
      overcome the limitations of DMARD monotherapy. The advent of biological therapies
      that specifically target key proinflammatory cytokines, believed to be important
      in disease pathogenesis, provides several new treatment options. In controlled
      clinical trials, the IL-1 blocker anakinra (r-metHuIL-1ra) significantly reduced
      the clinical signs and symptoms of RA when used alone or in combination with
      weekly methotrexate. The TNF inhibitors etanercept, infliximab and adalimumab
      have shown similar efficacy; indeed, higher response rates for clinical and
      radiological parameters have been seen with the TNF blockers. Importantly, each
      of these biological response modifiers significantly reduced radiographic disease
      progression in 6- to 12-month studies, and some radiographic data extend to 24
      months. Despite these promising findings, it remains to be determined whether
      slowing radiographic progression will translate into significant improvements in
      long-term outcomes.

PMID- 15150429
TI  - Increased entry of CD4+ T cells into the Th1 cytokine effector pathway during T
      cell division following stimulation in Behcet's disease.
AB  - OBJECTIVES: To investigate the relationship between the production of Th1/Th2
      cytokines and cell kinetics, cell division and proliferation in patients with
      Behcet's disease (BD). METHODS: Peripheral venous blood was drawn from patients
      with BD (n = 24; 10 patients with active and 14 patients with inactive BD) and
      normal subjects (n = 22). Peripheral blood mononuclear cells were separated
      immediately and were cultured with concanavalin A (Con A) followed by phorbol 12
      myristate 13-acetate and ionomycin (PMA+Ion). Intracellular cytokine production
      of interferon-gamma (IFN-gamma) (Th1) and IL-4 (Th2) in CD4(+) T cells was
      determined by flow cytometry. Furthermore, CD4(+) T cells labelled with CFSE [5
      (and 6) carboxyfluorescein diacretate, succinimidyl ester] were stimulated and
      the cells were analysed for entry into the cytokine production effector pathway
      during cell division in active BD and normal subjects. RESULTS: In active BD,
      enhanced entry into the Th1 response effector pathway of CD4(+) T cells was
      observed after stimulation with Con A followed by PMA+Ion. Analysis of CD4(+) T
      cells at an identical cell division number in response to Con A followed by
      PMA+Ion revealed that IFN-gamma-producing cells were increased in active BD
      patients compared with normal subjects. These results suggest that the Th1
      response of dividing CD4(+) T cells is predominantly operating in active BD.
      Dividing CD4(+) T cells stimulated with Con A followed by PMA+Ion showed a
      phenotype of activated effector memory T cells (CD45RA(low), CD45RO(+),
      CD69(high)). CONCLUSIONS: Cell kinetics play a crucial role in Th1 cell
      differentiation and pathophysiology in BD.

PMID- 15150430
TI  - Risk of coronary heart disease and stroke in a large British cohort of patients
      with systemic lupus erythematosus.
AB  - OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are at increased
      risk of myocardial infarction and stroke. We sought to determine how much of this
      risk was dependent on recognized cardiovascular risk factors. METHODS: Initially
      a software package 'Cardio-Risk-Manager', which utilizes Framingham data, was
      used to calculate a 10-yr risk of coronary heart disease (CHD) and stroke for 202
      patients with SLE (Group 1) in comparison with hypothetical age- and sex-matched
      comparators. Subsequently 47 patients who had been followed since 1991 (Group 2)
      were studied to compare their predicted risks in 1991 with the actual number of
      cardiovascular events that occurred during the subsequent decade. RESULTS:
      Patients in Group 1 had a higher predicted 10-yr risk of stroke (P<0.0001), but
      not of CHD, than their comparators. However, following age stratification,
      traditional risk factors predicted a higher risk of CHD (P<0.0001) and of stroke
      (P<0.0001) in patients under 40 with SLE compared with age-matched comparators.
      The predicted 10-yr risks of CHD and stroke for patients aged 40 and above were
      not significantly different from those of their comparators. Predicted risks,
      however, were lower than the true 10-yr event rate for CHD and stroke in patients
      in Group 2. In this group, during the 10 yr of follow-up four patients (8.5%)
      suffered a CHD event and five patients (10.6%) had a stroke, significantly more
      than were predicted by the presence of conventional risk factors (P<0.001 for CHD
      and P<0.001 for stroke, respectively). CONCLUSIONS: Conventional risk factors
      predicted an increased risk of stroke and CHD in younger patients. They do not,
      however, fully explain the high risk of cardiovascular disease in patients with
      SLE. Although it is important to address the management of orthodox risk factors
      for cardiovascular disease in patients with SLE, other causes must be sought to
      explain the increased incidence of CHD and stroke, especially in those aged over
      40.

PMID- 15150431
TI  - Transitional care for adolescents with juvenile idiopathic arthritis: a Delphi
      study.
AB  - OBJECTIVE: To identify the ideal programme of transitional care for adolescents
      with juvenile idiopathic arthritis (JIA) as perceived by users and providers, and
      to examine the feasibility of achieving this within a UK National Health Service
      context. METHODS: A modified two-stage Delphi study was undertaken with
      rheumatology health professionals, young people with JIA (aged 12-25 yr) and
      their parents. Participants were presented with statements about transitional
      care and asked to rate (i) the extent to which these constituted best practice,
      and (ii) their feasibility. RESULTS: Second-round questionnaires were completed
      by 83 individuals, representing an overall response rate of 90%. Items strongly
      agreed to constitute best practice and highly feasible included: 'addressing
      young people's psychosocial and educational/vocational needs'; 'using an
      individualized approach'; 'providing honest explanations of the adolescent's
      condition and health-care'; 'providing opportunities for adolescents to express
      opinions and make informed decisions'; 'having continuity in health personnel';
      and 'giving adolescents the option of being seen by professionals without their
      parents'. However, providing adolescent-focused environments, professionals
      knowledgeable in transitional care and opportunities for young people with JIA to
      meet similar others were seen as feasible in only a few hospitals. CONCLUSIONS:
      There is considerable agreement as to the most important elements of transitional
      care. Those that are easily achievable should be undertaken in all hospitals that
      care for adolescents with JIA. However, not all elements identified were
      perceived as easily feasible; further research is required to determine how to
      implement these elements.

PMID- 15150432
TI  - Atherosclerosis and lupus.

PMID- 15150434
TI  - Poststreptococcal reactive arthritis: what is it and how do we know?
AB  - OBJECTIVE: To find out whether poststreptococcal reactive arthritis (PSRA) is a
      discrete, homogeneous clinical syndrome. METHOD: Literature review from case
      reports and case series. RESULTS: One hundred and eighty-eight cases were
      identified. The age distribution was bimodal, with one peak in childhood and one
      peak in adulthood. Eighty-three percent of streptococcal isolates were group A.
      The clinical presentation was heterogeneous but appeared different both from that
      of acute rheumatic fever (ARF) and from that of HLA B27-associated reactive
      arthritis. Carditis was rare. CONCLUSIONS: The term PSRA encompasses significant
      heterogeneity. The link between the arthritis and the streptococcal infection is
      unproven.

PMID- 15150435
TI  - Typical and atypical Cogan's syndrome: 32 cases and review of the literature.
AB  - OBJECTIVE: To report our experience on a multicentre series of 32 patients with
      either typical or atypical Cogan's syndrome, to combine our results with a
      detailed review of the literature, and to compare the clinical manifestations of
      typical and atypical Cogan's syndrome. METHODS: Patients were identified from a
      survey conducted with physicians affiliated to the French National Society for
      Internal Medicine, and were classified into typical or atypical Cogan's syndrome
      according to the Haynes criteria. Clinical data were collected in a standardized
      manner. A comprehensive literature review using the Medline database and the
      reference lists of identified articles was performed. RESULTS: Seventeen patients
      had typical Cogan's syndrome and 15 had atypical Cogan's syndrome. Apart from non
      syphilitic interstitial keratitis, the ocular manifestations of patients with
      atypical Cogan's syndrome were mainly uveitis and episcleritis. All but one
      patient presented with Meniere-like syndrome, and at the end of follow-up 11 were
      deaf and 19 additional patients had developed a significant decrease in auditory
      acuity. Twenty-five patients (78%) developed systemic manifestations, including
      aortitis in four. Comparison of typical and atypical Cogan's syndrome showed that
      some systemic manifestations were more common in atypical Cogan's syndrome, but
      these differences may be explained by reporting bias in the literature.
      CONCLUSION: Differences regarding the associated systemic manifestations of
      typical and atypical Cogan's syndrome may reflect reporting bias in the
      literature. However, the diversity of the ocular and audiovestibular
      manifestations and the acceptable lengthy delay between the two types of
      involvement in atypical Cogan's syndrome should make one cautious before
      accepting this diagnosis as the diagnosis may mimic various other systemic
      diseases.

PMID- 15150433
TI  - Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic
      ELR+ chemokine genes relate to course of arthritis.
AB  - OBJECTIVE: To evaluate the ability of microarray-based methods to identify genes
      with disease-specific expression patterns in peripheral blood mononuclear cells
      (PBMC) and synovial fluid mononuclear cells (SFMC) of juvenile arthritis patients
      and healthy controls. METHODS: Microarray data (Affymetrix U95Av2) from 26 PBMC
      and 20 SFMC samples collected from patients with active disease (classified by
      course according to ACR criteria) were analysed for expression patterns that
      correlated with disease characteristics. For comparison, PBMC gene expression
      profiles were obtained from 15 healthy controls. Real-time PCR was used for
      confirmation of gene expression differences. RESULTS: Statistical analysis of
      gene expression patterns in PBMC identified 378 probe sets corresponding to 342
      unique genes with differing expression levels between polyarticular course
      patients and controls (t test, P<0.0001). The genes represented by these probe
      sets were enriched for functions related to regulation of immune cell functions,
      receptor signalling as well as protein metabolism and degradation. Included in
      these probe sets were a group of CXCL chemokines with functions related to
      angiogenesis. Further analysis showed that, whereas angiogenic CXCL (ELR+) gene
      expression was elevated in polyarticular PBMC, expression of angiostatic CXCL
      (ELR-) chemokines was lower in polyarticular SFMC compared with corresponding
      pauciarticular samples (t test, P<0.05). CONCLUSIONS: This pilot study
      demonstrates that juvenile arthritis patients exhibit complex patterns of gene
      expression in PBMC and SFMC. The presence of disease-correlated biologically
      relevant gene expression patterns suggests that the power of this approach will
      allow better understanding of disease mechanisms, identify distinct clinical
      phenotypes in disease subtypes, and suggest new therapeutic approaches.

PMID- 15150436
TI  - Patients' perceptions of treatment with anti-TNF therapy for rheumatoid
      arthritis: a qualitative study.
AB  - OBJECTIVES: Anti-tumour necrosis factor (anti-TNF) therapy is a highly effective
      treatment for rheumatoid arthritis (RA), as documented using standard outcome
      measures in clinical trials. Anecdotal experience suggests health benefits for
      patients other than those measured in this way. We wished to explore Patients'
      experience of and views about this treatment and the British Society for
      Rheumatology Biologics Registry (BSR BR) process. METHODS: Separate focus groups
      for patients treated with infliximab (n = 7) and etanercept (n = 12) were
      undertaken. They were taped and transcribed verbatim, analysed and subjected to
      peer review and themes were identified. RESULTS: Five main themes were
      identified: expectations of treatment, experience of treatment and its effects,
      concerns about taking a new class of drug, views about the BSR Biologics Registry
      process and costs. CONCLUSIONS: Patients' experience of anti-TNF therapy was
      good, particularly in terms of physical function and well-being, although it did
      not live up to the very high expectations of some patients. The BSR BR process
      caused initial apprehension but patients had personal and altruistic reasons for
      being happy to comply with monitoring requirements. Qualitative methods add to
      our understanding of the effects of anti-TNF therapy for people with RA.

PMID- 15150438
TI  - Association study of the angiotensin-converting enzyme (ACE) gene G2350A
      dimorphism with myocardial infarction.
AB  - The angiotensin converting enzyme (ACE) is a strong candidate gene for myocardial
      infarction (MI). Insertion-deletion dimorphism in intron 16 of this gene has been
      inconclusively found to be associated with it. Several new polymorphisms in the
      ACE gene have been identified and among these, a dimorphism in exon 17, ACE
      G2350A, has a significant effect on plasma ACE concentrations. To assess the
      value of genotyping the ACE G2350A dimorphism in a genetically homogeneous
      population, we carried out a case-control study of dimorphism G2350A for a
      putative association with MI among Pakistani nationals. We investigated a sample
      population of 370 Pakistanis, comprising 163 controls, and 207 patients with
      clinical diagnosis of acute MI (AMI). ACE G2350A alleles were visualized by
      assays based on polymerase chain reaction and restriction endonuclease analysis.
      Frequencies of G alleles were 0.68 among controls and 0.72 among AMI patients.
      The ACE G2350A dimorphism showed no significant association with MI (chi2 = 0.90,
      2 df, P = 0.64), plasma levels of homocysteine (P = 0.52) or with serum levels of
      folate (P = 0.299). The results indicate that ACE G2350A polymorphism is not
      associated with risk of myocardial infarction in the Pakistani population
      investigated here.

PMID- 15150437
TI  - Phospholipase D is involved in oxidative stress-induced migration of vascular
      smooth muscle cells via tyrosine phosphorylation and protein kinase C.
AB  - Oxidative stress has been implicated in mediation of vascular disorders. In the
      presence of vanadate, H(2)O(2) induced tyrosine phosphorylation of PLD1, protein
      kinase C-alpha (PKC-alpha), and other unidentified proteins in rat vascular
      smooth muscle cells (VSMCs). Interestingly, PLD1 was found to be constitutively
      associated with PKC-alpha in VSMCs. Stimulation of the cells by H(2)O(2) and
      vanadate showed a concentration-dependent tyrosine phosphorylation of the
      proteins in PLD1 immunoprecipitates and activation of PLD. Pretreatment of the
      cells with the protein tyrosine kinase inhibitor, genistein resulted in a dose
      dependent inhibition of H(2)O(2)-induced PLD activation. PKC inhibitor and down
      regulation of PKC abolished H(2)O(2)-stimulated PLD activation. The cells
      stimulated by oxidative stress (H(2)O(2)) caused increased cell migration. This
      effect was prevented by the pretreatment of cells with tyrosine kinase
      inhibitors, PKC inhibitors, and 1-butanol, but not 3-butanol. Taken together,
      these results suggest that PLD might be involved in oxidative stress-induced
      migration of VSMCs, possibly via tyrosine phosphorylation and PKC activation.

PMID- 15150440
TI  - Microsatellite instability and its correlation with clinicopathological features
      in a series of thyroid tumors prevalent in iodine deficient areas.
AB  - Thyroid tumors display diverse spectrum of histopathological groups with
      geographic variation in its prevalence. Influence of iodine deficiency (a major
      causative factor) in its etiology, prevalence, or aggressiveness is debatable
      which reflects the existence of various genetic events in pathogenesis. The
      present study was undertaken to study the role of Microsatellite instability
      (MSI) or LOH (loss of heterozygosity), an indicator of defective mismatch repair
      system as a genetic change and to explore it as a prognostic marker in thyroid
      tumors. Tumor tissues from total thyroidectomy surgical specimens and blood
      (matched control) of 36 patients from iodine deficient areas (10 benign; 26
      malignant) were obtained after their consent. Urinary iodine analysis was done by
      alkali ash method for which 10 ml of urine was collected from 18 patients before
      surgery. Genomic DNA, isolated from tumor tissue and blood was amplified by
      polymerase chain reaction (PCR) using mono and dinucleotide markers - BAT-26, BAT
      40, TGF(RII, IGFIIR, hMSH3, BAX, D2S123, D9S283, D9S851 and D18S58. PCR products
      were analysed on 8% denaturing polyacrylamide gel followed by autoradiography. Of
      total, 66.6% of tumors [70% (7/10) benign and 65.4% malignant cases (17/26)]
      showed MSI/LOH. Strong association of MSI/LOH with low iodine (P = 0.01) and with
      AMES risk groups i.e. age (P = 0.02), tumor size (P = 0.04) and metastases (P =
      0.002) in thyroid tumors was observed. This may help in predicting the biological
      behaviour and strengthening the hypothesis that iodine deficiency has influence
      on MSI in thyroid tumors. Our results further substantiate the risk group
      classification and help in deciding the treatment modality in particular patient.

PMID- 15150439
TI  - Methylenetetrahydrofolate reductase polymorphism, diet, and breast cancer in
      Korean women.
AB  - To evaluate the interactive effect of methylenetetrahydrofolate reductase (MTHFR)
      genotype and dietary factors on the development of breast cancer, a hospital
      based case-control study was conducted in South Korean study population
      consisting of 189 histologically confirmed incident breast cancer cases and their
      189 age-matched controls without present or previous history of cancer. A PCR
      RFLP method was used for the genotyping of MTHFR (C677T) and statistical
      evaluations were performed by unconditional logistic regression analysis.
      Consumption of some dietary factors, such as green vegetables (OR = 0.3, 95% CI:
      0.2-0.6), white vegetables (OR = 0.3, 95% CI: 0.1-0.7) mushrooms (OR = 0.4, 95%
      CI: 0.3-0.7), and meats (OR = 1.7, 95% CI: 1.1-2.8) significantly decreased or
      increased the risk of breast cancer. Although the breast cancer risk was 1.7-fold
      (95% CI: 0.8-3.2) increased in women with MTHFR TT genotype, the association was
      not statistically significant. Women with MTHFR TT genotype and low green
      vegetable intake increased 5.6-fold (95% CI: 1.2-26.3) risk of breast cancer
      compared to high green vegetable intake group containing MTHFR CC/CT genotype.
      However, the interaction was not significant (p for interaction = 0.96). Our
      findings suggest that MTHFR polymorphism did not influence individual
      susceptibility to breast cancer. However MTHFR (C667T) genotype and green
      vegetable intakes appeared to have the interactive effect in breast cancer
      development.

PMID- 15150441
TI  - Nerve growth factor (NGF) induces mRNA expression of the new transcription factor
      protein p48ZnF.
AB  - Apoptosis, the cell's intrinsic death program, plays a crucial role in the
      regulation of tissue homeostasis, and abnormal inhibition of apoptosis is an
      indicator of cancer and autoimmune diseases, whereas excessive cell death is
      implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using
      cDNA subtraction analysis, we compared p60TRP (p60 transcription regulator
      protein) expressing cells with control cells during the process of apoptosis and
      we identified the new zinc-finger protein p48ZnF that is predominantly located in
      the cytoplasm of the cell. Additionally, we demonstrate here that p48ZnF is up
      regulated in rat neuronal PC12 cells upon stimulation with the neurotrophic
      factor NGF (50 ng/ml). These findings point to a possible pivotal role of p48ZnF
      in the control of neuronal survival.

PMID- 15150442
TI  - Trp-Lys-Tyr-Met-Val-Met stimulates phagocytosis via phospho-lipase D-dependent
      signaling in mouse dendritic cells.
AB  - Dendritic cells (DCs) play a key role in activating the immune response against
      invading pathogens as well as dying cells or tumors. Although the immune response
      can be initiated by the phagocytic activity by DCs, the molecular mechanism
      involved in this process has not been fully investigated. Trp-Lys-Tyr-Met-Val-Met
      NH(2) (WKYMVM) stimulates the activation of phospholipase D (PLD) via Ca(2+)
      increase and protein kinase C activation in mouse DC cell line, DC2.4. WKYMVM
      stimulates the phagocytic activity, which is inhibited in the presence of N
      butanol but not t-butanol in DC2.4 cells. Furthermore, the addition of
      phosphatidic acid, an enzymatic product of PLD activity, enhanced the phagocytic
      activity in DC2.4 cells. Since at least two of formyl peptide receptor (FPR)
      family (FPR1 and FPR2) are expressed in DC2.4 as well as in mouse bone marrow
      derived dendritic cells, this study suggests that the activation of FPR family by
      WKYMVM stimulates the PLD activity resulting in phagocytic activity in DC2.4
      cells.

PMID- 15150443
TI  - Evidence that the fully assembled capsid of Leishmania RNA virus 1-4 possesses
      catalytically active endoribonuclease activity.
AB  - In this study, Leishmania RNA virus 1-4 (LRV1-4) particles purified from host
      Leishmania guyanensis promastigotes were examined for capsid endoribonuclease.
      Temperature optimum for the endoribonuclease activity was found to be at 37(O)C
      to 42(O)C and the activity was specifically inhibited by the aminoglycoside
      antibiotics, neomycin, kanamycin, and hygromycin and by 100 mM levels of NaCl or
      KCl. To determine the catalytic domain of the capsid endoribonuclease activity,
      three point-mutation at cysteine residues at C47S (P1), C128/ 133S (P2), and
      C194R (P3) were prepared and each gene was constructed into baculoviruses and
      expressed in Sf9 insect cells. LRV1-4 capsid N- terminus (N2 and N3) and C
      terminus (C1 and C2) deletion mutants (Cadd et al., 1994) were also examined by
      in vitro RNA cleavage assay. The results showed that the capsid mutants; C1, C2,
      N3, P1, and P2 were capable of forming proper virus-like particles (VLPs) and
      they all possessed the specific endoribonuclease activity. However, two assembly
      defective capsid mutants, N2 (N- terminus 24-amino acids deletion) and P3
      mutants, did not retain the specific endoribonuclease activity. Taken together,
      the results suggest that at least 24 amino acids from the N-terminal region and
      C194 residue in LRV1-4 capsid protein are functionally important for LRV1-4 viral
      assembly and the capsid endoribonuclease activity may be dependent upon the
      properly assembled LRV1-4 virus particles.

PMID- 15150444
TI  - Involvement of ROS and JNK1 in selenite-induced apoptosis in Chang liver cells.
AB  - Selenium is a dietary essential trace nutrient with important biological roles.
      Selenocompounds were reported to induce apoptosis in many types of tumor cells.
      In this study, we investigated the signaling pathway involved in the selenite
      induced apoptosis using Chang liver cells as a non-malignant cell model. The
      Chang liver cell apoptosis induced by selenite (10 microM) was confirmed by DNA
      fragmentation and typical apoptotic nuclear changes. Treatment of selenite
      increased intracellular reactive oxygen species (ROS) level and c-Jun N-terminal
      kinase1 (JNK1) phosphorylation. The selenite-induced cell death was attenuated by
      SP600125, a specific inhibitor of JNK, and by dominant negative JNK1 (DN-JNK1).
      Antioxidants such as glutathione (GSH), N-acetyl cysteine (NAC), curcumin,
      epigallocatechin gallate (EGCG) and epicatechin (EC) inhibited selenite-induced
      intracellular ROS elevation and JNK1 phosphorylation. Our results suggest that
      selenite-induced apoptosis in Chang liver cells was preceded by the ROS
      generation and JNK1 activation.

PMID- 15150445
TI  - Inactivation patterns of p16/INK4A in oral squamous cell carcinomas.
AB  - The p16/INK4A is one of the major target genes in carcinogenesis and its
      inactivation has frequently been reported in other types of tumors. The purpose
      of this study is to evaluate inactivation patterns of p16/INK4A in oral squamous
      cell carcinoma. Six different oral cancer cell lines, SCC-4, SCC-9, SCC-15, SCC
      25, KB, and SNUDH- 379 were examined for inactivation of p16/INK4A genes. In the
      analysis of p16/INK4A gene inactivation, PCR amplification, direct sequencing,
      and methylation-specific PCR methods were adopted for evaluation of homozygous
      deletion, point mutation, and promoter hypermethylation, respectively. Homozygous
      deletion was detected in SCC-25 and SCC-9. SCC-15 showed hypermethylated promoter
      region within p16/INK4A gene. It is suggestive in the present study that
      inactivation patterns of p16/INK4A were mainly homozygous deletion, promoter
      methylation rather than point mutation in oral squamous cancer cell lines, so
      treatment modalities of oral squamous cell carcinoma should be focused on these
      types of inactivation.

PMID- 15150446
TI  - Phosphorylation of phospholipase D1 and the modulation of its interaction with
      RhoA by cAMP-dependent protein kinase.
AB  - Agents that elevate cellular cAMP are known to inhibit the activation of
      phospholipase D (PLD). We investigated whether PLD can be phosphorylated by cAMP
      dependent protein kinase (PKA) and PKA-mediated phosphorylation affects the
      interaction between PLD and RhoA, a membrane regulator of PLD. PLD1, but not PLD2
      was found to be phosphorylated in vivo by the treatment of dibutyryl cAMP
      (dbcAMP) and in vitro by PKA. PKA inhibitor (KT5720) abolished the dbcAMP-induced
      phosphorylation of PLD1, but dibutyryl cGMP (dbcGMP) failed to phosphorylate
      PLD1. The association between PLD1 and Val14RhoA in an immunoprecipitation assay
      was abolished by both dbcAMP and dbcGMP. Moreover, RhoA but not PLD1 was
      dissociated from the membrane to the cytosolic fraction in dbcAMP-treated cells.
      These results suggest that both PLD1 and RhoA are phosphorylated by PKA and the
      interaction between PLD1 and RhoA is inhibited by the phosphorylation of RhoA
      rather than by the phosphorylation of PLD1.

PMID- 15150449
TI  - Integrated care: hospice and palliative care services lead the way.

PMID- 15150448
TI  - Proteomic analysis of human cerebral cortex in epileptic patients.
AB  - Epilepsy affects more than 0.5% of the world population and is known to be
      associated with a large genetic component eliciting an electrical
      hyperexcitability in the central nervous system. However, its pathogenic
      mechanisms remain poorly understood. In order to gain greater molecular incite in
      the pathogenesis in epilepsy, we analyzed proteomes of human cerebral cortices.
      Quantitative proteome analysis was used to compare signals corresponding to
      individual proteins between epileptic cerebral cortices from patients with
      temporal lobe epilepsy and age-matched non-epileptic subjects. To minimize
      individual variations, gender and age of the patients were matched. Changes of
      several spots were consistent among 6 pairs of epileptic patients and
      nonepileptic subjects. One of the spots was identified as the mitochondrial type
      Mn-superoxide dismutase (Mn-SOD) confirmed by Western blot analysis with Mn-SOD
      antibody and enzyme activity assay. Such results were agreeable with chemical and
      physical parameters given by the 2-dimensional electrophoresis (2-DE) gel. Mn-SOD
      was consistently down-regulated in epileptic cerebral cortices compared with
      those of nonepileptic subjects. Our results demonstrate a clear link between
      pathogenesis of epilepsy and SOD. Additionally, we identified four proteins that
      were consistently over-expressed in all epileptic temporal neocortices specimens
      and the other four proteins that were found to be expressed less than non
      epileptic control subjects. These proteomic data provide cellular markers in the
      understanding mechanism of the epilepsy pathogenesis.

PMID- 15150447
TI  - Application of DNA chip techniques for Yq microdeletion analysis in infertile
      males.
AB  - Our aim was to apply DNA chip technology as a diagnostic tool in infertility
      research and clinics. Six loci, including a sex-determining region on the Y
      chromosome and five sequence-tagged sites in azoospermia-factor regions were
      investigated in infertile male patients. Our method produced a sensitive signal,
      which showed the presence or absence of the STS regions on the Y chromosome. The
      results from 93 patients with non- obstructive azoospermia,
      oligoathenoteratozoospermia, or oligozoospermia were identical when analyzed with
      either the DNA chip technique or conventional PCR-gel electrophoresis. We have
      demonstrated its application in the molecular diagnosis of male infertility. This
      system provides an economic and high-throughput method for detecting the deletion
      of genomic DNA sequences of large groups of infertile patients, and a completely
      new approach to male infertility screening. The application of DNA chip
      technology to identify Yq deletions can also facilitate our understanding of male
      infertility.

PMID- 15150451
TI  - Do nurses respect themselves enough?

PMID- 15150450
TI  - Perceptions of spiritual care among nurses undertaking postregistration
      education.
AB  - Previous research has suggested that qualified nurses recognize that patients
      have spiritual needs and consider meeting those needs to be important. However,
      there is also evidence suggesting that nurses feel ill prepared for, and
      uncertain about, their role as spiritual care providers. A questionnaire on
      spiritual care and the nurse's role was distributed to a group of 59 registered
      nurses (of varying ages and levels of experience) undertaking a palliative care
      module as part of a post-registration degree programme in Scotland. The findings
      demonstrated that respondents regarded spiritual care as important, especially
      for certain patient groups. They also thought nurses had a significant
      responsibility in spiritual caregiving. Individuals varied in how difficult they
      found identifying patients in need of spiritual care and in meeting those needs.
      However, analysis of responses revealed considerable insight into possible signs
      of patient need, examples of nursing interventions and potential barriers to
      effective spiritual care. Some areas of relative lack of knowledge were
      identified and may indicate where future efforts to raise awareness of spiritual
      care among similar groups of nurses should be concentrated.

PMID- 15150452
TI  - Dignity-conserving care: application of research findings to practice.
AB  - A central tenet of palliative care is to help people die with "dignity". The
      widespread use of this term presupposes that this construct is well understood
      from the perspective of the terminally ill, and that the factors that bolster or
      erode dignity are known. However, the paucity of research related to these issues
      suggests otherwise. Over the past 5 years, this research team, headed by Dr
      Chochinov, has undertaken a programme of research aimed at explicating what
      dignity means to those who are terminally ill, and identifying those factors that
      support and undermine dignity in this patient population. This article will
      provide a synopsis of that work, with an emphasis on the application of research
      findings for practice.

PMID- 15150453
TI  - A difficult relationship between oncology ward staff and a patient's husband: a
      case study.

PMID- 15150454
TI  - Attitudes towards end-of-life care in a geriatric hospital in Japan.
AB  - Nursing and medical staff attitudes toward end-of-life care at a private, not-for
      profit geriatric hospital in Japan were measured as part of a larger intervention
      study to develop a palliative care programme. The intervention consisted of focus
      groups, education with pre- and post-testing, and attitude/belief surveys. All
      the medical staff (n = 8) and 99% (n = 97) of the nursing staff participated.
      Nursing staff overwhelmingly agreed that a palliative care programme would
      improve end-of-life care (94.6%) and that nurses should be more involved in
      discussing treatment options with families (85.7%). Of the nursing staff, 88.7%
      did not agree that doctors currently spend enough time discussing care plans with
      patients/families. The main barriers to improving end-of-life care perceived by
      the nursing staff were the treatment-oriented attitude of the doctors and their
      limited communication skills. The main barriers perceived by doctors were the
      lack of alternatives to their medical approach and legal concerns. The findings
      suggest that improving doctor/nurse communication would facilitate the
      development of a palliative care programme at this hospital.

PMID- 15150455
TI  - Palliative care for children in the Republic of Belarus.

PMID- 15150456
TI  - Reflections on the contribution of Frances Sheldon.

PMID- 15150457
TI  - Should patient dignity prevail over nurses' risk of injury?

PMID- 15150458
TI  - Clinical skills: the physiological basis and interpretation of the ECG.
AB  - Electrocardiograph (ECG) interpretation is a complex subject that requires
      considerable experience. However, an understanding of the principles underlying
      generation of the ECG can make this learning process easier. This knowledge is
      necessary if interpretation is to be founded on understanding rather than being a
      pattern recognition-based process. The aim of this article is to introduce the
      practitioner to the basic processes and mechanisms that govern formation of the
      normal ECG. These principles will largely be applied to the normal ECG and
      include cardiac anatomy applied to the ECG, how the ECG leads look at the heart
      and how the normal ECG waveform is formed. Examples of how the ECG changes when
      the underlying mechanisms are disturbed will also be given. Together, this
      knowledge should help the practitioner to have a clearer understanding of
      interpreting the abnormalities seen on an ECG.

PMID- 15150459
TI  - Management options for patients with intermittent claudication.
AB  - Peripheral arterial disease is a chronic condition, affecting a significant
      proportion of the adult population. Intermittent claudication is the earliest
      clinical manifestation of peripheral arterial disease and the patient's walking
      distance can be significantly reduced. This restriction can profoundly disrupt
      activities of living. Treatment options vary according to the level of the
      disease and co-morbidity of the patient. Current evidence to support risk factor
      assessment highlights the role of the nurse in encouraging lifestyle
      modification.

PMID- 15150460
TI  - The role of exercise training in patients with chronic heart failure.
AB  - The National Institute for Clinical Excellence (NICE) has recommended that
      exercise training be offered to patients with chronic heart failure (CHF). This
      recommendation is supported by research-based evidence from a variety of studies
      over the past 10 years. Initially, the studies were concerned primarily with the
      safety and effectiveness of exercise in these high-risk patients, but more recent
      studies have begun to investigate the most appropriate methods of exercise for
      this patient population. This article presents a systematic review of the
      literature relating to exercise training and CHE. It then attempts to identify,
      in light of the evidence, the most effective programme of exercise, including
      type, duration and degree of exercise. Finally, it discusses practical
      application and implementation of the research findings into everyday health
      care, including issues such as staff development and training, assessment,
      exercise and prescription for individual patients, and evaluation of the service.

PMID- 15150461
TI  - Management of scrotal swelling after pelvic and acetabular fractures.
AB  - Complex pelvic and acetabular fractures are usually associated with high-energy
      trauma and often present with substantial perineal soft tissue swelling. This is
      the result of the significant haemorrhage that develops into the retroperitoneal
      space, which dissects along fascial planes to extend into the scrotum. Other
      factors that could contribute to the progression of the soft tissue swelling
      include the extensive approaches used for surgical stabilization of the
      fractures, the prolonged traction using a perineal post and the early typical
      catabolic responses after major trauma. This article describes a successful
      protocol for the management of scrotal swelling associated with complex pelvic
      and acetabular fractures. Rapid reduction of the swelling in the scrotal region
      prevents the onset of perineal wound slough. It also minimizes the risk of
      infection in case of skin breakdown by isolation from the perianal region.
      Furthermore, it precludes friction of the scrotum with the skin of the thigh,
      thus allowing adequate pain relief and faster rehabilitation.

PMID- 15150462
TI  - The human right to dignity v. physical integrity in manual handling.
AB  - In the case of The Queen v. East Sussex County Council and The Disability Rights
      Commission [2003] the position in English and European Law with regard to the
      rights of disabled people to be lifted manually in their homes was reviewed. The
      judgement also reviewed the position with regard to the risks posed to carers
      when they manually lift. The judgement stated that where the human rights of
      disabled people were in issue--where their Article 8 right to "dignity" was
      offended--then carers would in certain situations have to find ways to lift those
      people manually. This article reviews and challenges the findings in this case. A
      conclusion is reached that a reading of English and European law does not suggest
      that nurses and carers can be expected to be caused a physical harm to their
      persons, in order to assuage the "dignity" rights of those they lift. Further,
      that issues such as insurance and compensation, possibly owing to a nurse who
      manually lifts, have not been settled, and that all of these issues have not been
      determined where lifting occurs manually in a hospital setting.

PMID- 15150463
TI  - Deputy matron who physically and verbally abused patients in her care.

PMID- 15150464
TI  - Integrating foot care into the everyday clinical practice of nurses.
AB  - Foot care is an integral part of a patient's daily hygiene requirements, yet the
      authors have found it to be an area often neglected by nurses. Foot and toenail
      problems present a considerable challenge to nurses in all healthcare settings,
      especially for patients with diabetes. However, patients without diabetes also
      suffer from minor foot abnormalities or injuries that might have been
      preventable. One acute hospital ward has worked closely with the chiropody
      department to improve the nursing team's competence and confidence in foot
      hygiene assessment and toenail clipping and has, therefore, improved the patient
      experience during hospital admission. This article describes how the nursing team
      used education to improve the foot care services offered to patients.

PMID- 15150465
TI  - Infection control: maintaining the personal hygiene of patients and staff.
AB  - This article concentrates on the importance of personal hygiene for staff and
      patients in reducing the risk of healthcare-associated infections for patients.
      It provides an historical context to the associated risks of "basic nursing care"
      and how these can be counteracted. With the introduction of modern matrons and
      directors of infection control, emphasis is again focused on these practices.

PMID- 15150466
TI  - Nurses must learn methods to deal with difficult doctors.

PMID- 15150467
TI  - The law and the certification, verification and registration of death.
AB  - Daisy was a registered nurse who worked in a community hospital. One night, Gwen,
      who was 85 years old, died and Daisy phoned the GP who was responsible for
      providing a service to the hospital. She was told that the GP did not come out at
      night for a death but would come in the morning. Daisy wanted the patient moved
      from the four-bedded ward to the mortuary, but was told that the procedures did
      not permit that until a doctor had certified the death. Daisy felt that it was
      unsettling to the other patients who knew that Gwen had died. What is the law?

PMID- 15150468
TI  - Decisions by nurses in acute care to undertake expanded practice roles.
AB  - Since 1992, expanded practice has been an important issue in the career
      progression of the qualified nurse. Its contemporary relevance in the early years
      of the 21st century is underpinned by recent and ongoing national initiatives to
      blur the boundaries between healthcare providers, and to regulate practice at a
      higher level. This article reports the findings of a survey and in-depth, semi
      structured interviews conducted with nurses from across the UK, which explores
      their views and experiences in terms of decisions regarding whether or not to
      undertake expanded practice roles. Insights are gained in a variety of domains of
      expanded practice including preparation for the role, competency verification,
      perceptions of accountability and liability, effects on patient care, role
      refusal and utilization of evidence to underpin expanded practice. These reported
      views and experiences have important implications for current practice and future
      research.

PMID- 15150469
TI  - When nurses take on doctors' roles are they just gap-filling?

PMID- 15150470
TI  - Nurses worried about the erosion of the caring role.

PMID- 15150471
TI  - Do physicians' assistants have a role in the UK?

PMID- 15150472
TI  - Role of hospital nursing in promoting patient recovery.

PMID- 15150473
TI  - Intra- and extracranial causes alteration in level of consciousness.
AB  - Acutely ill patients often demonstrate an altered level of consciousness.
      However, there are a variety of different reasons that may cause this alteration
      and nurses caring for patients without a defined cerebral event need to be aware
      of situations that can alter a patient's level of consciousness so that care
      strategies can be implemented. This article explains the concepts of
      consciousness and intracranial pressure and what is meant by an 'altered level of
      consciousness'. Assessment strategies are identified and a simple alternative to
      the Glasgow Coma Scale is identified that can be used as an initial assessment
      tool. This then allows the nurse caring for the patient with an altered level of
      consciousness to rationalize his/her intervention in relation to that patient.

PMID- 15150474
TI  - Current management of neurogenic bladder in patients with MS.
AB  - Multiple sclerosis (MS) is a common neurological problem and many sufferers are
      affected by urinary symptoms that negatively impact on their quality of life.
      Nurses are intimately involved in management of continence and other bladder
      problems with MS patients and need to be aware of appropriate assessment
      techniques and treatment options so that patients can be managed optimally.
      Nurses can have a significant role to play in reducing bladder symptoms and
      directly improving patients' quality of life. This article presents a review of
      current behavioural, pharmacological and surgical options for management of the
      neurogenic bladder in MS.

PMID- 15150476
TI  - Clinical skills: practical guide for managing adults with epilepsy.
AB  - This article concentrates on the practical management of those with seizures by
      general nurses. It focuses on the role of the hospital nurse in secondary care
      and the practice nurse in primary care. Both need to be conversant and
      practically competent to deal with the first-aid management of a seizure. They
      also need to know when medical assistance is required and how to act in an
      emergency. Epilepsy is a chronic long-term condition in adults and the main
      function of the nurse is advisory and educational. It is to act as a facilitator,
      and to assist adults to self-manage their epilepsy. Where the nurse is unable to
      provide this advice, appropriate referrals or contacts should be given.

PMID- 15150477
TI  - Are nurses nurses, doctors or a mixture of both?

PMID- 15150475
TI  - Assessment of chronic neuropathic pain and the use of pain tools.
AB  - Chronic neuropathic pain is experienced by a large number of patients. It can
      affect the individual physically, psychologically and socially. This review
      examines the evidence base for the assessment of chronic neuropathic pain and
      discusses some of the main tools and their suitability for use for this
      particular type of pain. The central role the nurse has in pain assessment and
      management to improve the patient's quality of life is explored. The evidence
      recommends that chronic pain be assessed using a multidimensional assessment
      tool. Currently the only tool specifically designed to measure neuropathic pain
      is the Neuropathy Pain Scale. The author describes how the evidence was applied
      to make changes in her own area of practice and why the Brief Pain Inventory was
      considered more suitable than the Neuropathy Pain Scale.

PMID- 15150478
TI  - Staff nurse who failed to provide adequate nursing care for patients.

PMID- 15150479
TI  - The clinical definition of death and the legal implications for staff.

PMID- 15150480
TI  - Older people and hypothermia: the role of the anaesthetic nurse.
AB  - Older clients are at increased risk during surgical intervention because of age
      related system changes and comorbid conditions. However, recent advances in
      surgical and anaesthetic techniques, together with modern monitoring technology
      and the proliferation of ambulatory surgery, have reduced mortality in older
      patients undergoing surgery. Nevertheless, inadvertent hypothermia in older
      clients remains problematic. Therefore, an understanding of specific diseases
      prevalent in old age, coupled with a comprehensive knowledge of the physiological
      impact of ageing in all body systems, underpins the role of the anaesthetic
      nurse.

PMID- 15150481
TI  - Hand hygiene: promoting compliance among nurses and health workers.
AB  - Around 10% of hospital patients acquire a healthcare-associated infection and it
      has been estimated that around one-third of these could be prevented. This
      article discusses the causal link between hand hygiene and infection and the
      reasons why healthcare workers (HCW) fail to comply with hand-hygiene policies.
      The action of hand hygiene is discussed in terms of the removal of transient
      micro-organisms and the agents used. Reasons for non-compliance and some measures
      for achieving compliance, such as education and patient empowerment, are
      discussed alongside the difficulties that these present. In order to move
      forward, it is suggested that the problem has to be managed through cultural
      change, making it easier for HCWs to comply by improving hand-cleansing
      facilities and materials and providing feedback to personnel on local infection
      rates so that high-priority areas can be targeted. This may be facilitated by
      locally based action research.

PMID- 15150482
TI  - Improving the quality of patient discharge from emergency settings.
AB  - This article describes a nurse-led telephone service that was introduced to
      improve the quality of patient discharge from the emergency assessment area (EAA)
      of a large NHS acute teaching trust. The service originated from concerns
      regarding the increasing volume of telephone enquiries received from patients
      after discharge. In addition, an audit of patients' discharge plans revealed a
      minimalist/cursory approach to documentation. To improve discharge practice, a
      nurse-led telephone follow-up was introduced for all patients within 24 hours of
      discharge from the EAA. Evaluation over the first 12 months demonstrated
      improvement in the quality of discharge documentation and more explicit discharge
      plans. The service has successfully addressed issues regarding follow-up
      arrangements, documentation, new prescribed medications and GP letters. For its
      second year of operation, the service has been refocused using criteria linked to
      a new 'patient-focused' discharge checklist before discharge, to determine who is
      most likely to need telephone follow-up.

PMID- 15150483
TI  - Promoting nursing, or hiding the truth?

PMID- 15150484
TI  - Alternative approaches to managing a non-draining urinary catheter.
AB  - Best practice in the management of indwelling catheters has been debated for many
      years. Proactive preventative strategies are widely considered favourable, but
      inevitably patients are referred with sudden, acute or unexpected non-draining
      catheters requiring a reactive or problem-solving response. This article
      considers the lack of comprehensive evidence on which nurses can base their
      practice when problems arise. It proposes that a clinical framework is necessary
      to guide nurses logically and rationally through the decision-making process. In
      addition, the case for diagnostic irrigation is assessed and the issue of
      catheter resiting as an alternative to recatheterization is highlighted.

PMID- 15150485
TI  - A multidisciplinary team approach to public health working.
AB  - For several years the government's health agenda has provided a strong directive
      for primary care professionals to work in a more public, health focused way.
      There remains, however, the constant challenge to incorporate a public health
      focus into existing clinical practice and caseload commitments in an achievable
      and manageable way, while at the same time impacting on ill health. This article
      explores a pragmatic public health approach to addressing some of the common
      health needs of people, as identified collectively in the national service
      frameworks for mental health, coronary heart disease, diabetes, older people and
      cancer. A practical example of facilitating collaborative working between
      disciplines and agencies is offered using the author's successful experiences
      form a review and modernization project of health visiting services in East
      Somerset (Dion, 2003).

PMID- 15150486
TI  - Keeping carers healthy: the role of community nurses and colleagues.
AB  - Carers form a substantial proportion of the patients seen by primary care
      professionals, but their health needs are often overlooked. By recognizing and
      addressing the needs of the carer as well as the patient, primary care staff
      (including practice, community and district nurses) can protect the physical and
      mental health of both. Staff can start by developing simple systems for
      identifying and recording both patients who are carers, and patient who have
      carers. Primary health professionals may be able to identify specific
      opportunities for checking on carers' health, e.g. at general health checks or
      clinics for older people or those with chronic disease. Community nurses should
      ensure that they use their home visits to keep an eye on the health of the carer
      as well as the patient. Much of this input can be integrated into the everyday
      activities and priorities of the primary care team.

PMID- 15150487
TI  - Statins and secondary prevention of coronary heart disease.
AB  - A mini-review (Griffiths, 2002) of double-blind randomized controlled trials
      (RCTs) was undertaken to assess the long-term effect of lipid lowering treatments
      (statins versus placebo) in secondary prevention of myocardial infarction (MI).
      The population sample was adult patients with a history of MI, documented
      coronary heart disease or coronary artery disease. The Cochrane Library and the
      database Medline were searched and three RCTs appeared to possess all of the
      stipulated inclusion and exclusion criteria. The trials all compared statins
      against a placebo; one trial was of simvastatin--the Scandinavian Simvastatin
      Survival Study (1994)--and the other two were of pravastatin--the Cholesterol and
      Recurrent Events Trial (CARE) (Sacks et al, 1996) and Long Term Intervention with
      Pravastatin Ischaemic Disease (LIPID) (Anon, 1998). The trials demonstrated that
      statins had a clear and consistent effect in significantly reducing the risk of
      MI. Overall an approximate decline of 30% in MI was produced from the three
      trials.

PMID- 15150488
TI  - Keeping secrets: confidentiality and the community nurse.

PMID- 15150489
TI  - Narrative approaches for research in community nursing.
AB  - As community nurses become more actively involved in practice-centred enquiry,
      they are increasingly exploring ways of understanding the lived experience of
      clients. Narrative approaches are becoming particularly prominent as these
      methods of enquiry closely connect with the regular interactions between client
      and nurse. In this article the nature of narrative and its use is outlined and
      illustrated with an example of narrative exploration. Additionally the article
      identifies some of the arguments for developing narrative approaches in primary
      health care and concludes with some discussion on challenges in using this
      approach.

PMID- 15150491
TI  - [Consensus conference: Complications of portal hypertension in adults. December
      2003].

PMID- 15150490
TI  - Medication errors should be avoided.

PMID- 15150492
TI  - [Evaluation and non-specific management of upper gastrointestinal bleeding due to
      rupture of esophageal varices].

PMID- 15150493
TI  - [Acute upper gastrointestinal variceal bleeding: vasoactive agents].

PMID- 15150494
TI  - [Gastrointestinal hemorrhage. What indications for endoscopic treatment?].

PMID- 15150495
TI  - [Gastrointestinal hemorrhage. Action to take if pharmacological and endoscopic
      treatments fail].

PMID- 15150496
TI  - [First episode of gastrointestinal bleeding, risk evaluation: when and how?].

PMID- 15150497
TI  - [How to prevent first variceal bleeding?].

PMID- 15150498
TI  - [Prevention and treatment of bleeding from gastric or ectopic varices or
      congestive gastropathy].

PMID- 15150499
TI  - [Gastrointestinal hemorrhage. How to prevent rebleeding: role of pharmacological
      and endoscopic treatments].

PMID- 15150500
TI  - [Gastrointestinal hemorrhage. Prevention of recurrent bleeding: modalities of
      endoscopic treatments].

PMID- 15150501
TI  - [Gastrointestinal hemorrhage. Does drug efficacy have to be checked? If so,
      how?].

PMID- 15150502
TI  - [Gastrointestinal hemorrhage. What can be done if drug and endoscopic treatments
      fail?].

PMID- 15150503
TI  - [How to treat a first episode of ascites?].

PMID- 15150504
TI  - [Treatment of refractory ascites].

PMID- 15150505
TI  - [Treatment of hepatorenal syndrome].

PMID- 15150506
TI  - [Treatment and prevention of ascitic fluid infection].

PMID- 15150507
TI  - [Management of hydrothorax].

PMID- 15150508
TI  - [Management of hepato-pulmonary syndrome].

PMID- 15150509
TI  - [Treatment of porto-pulmonary hypertension].

PMID- 15150510
TI  - [Gastrointestinal hemorrhage. Evaluation and non specific treatment].

PMID- 15150511
TI  - [Vasoactive drugs for the treatment of bleeding esophageal varices].

PMID- 15150513
TI  - [Gastrointestinal hemorrhage. Failure of pharmacological and endoscopic
      treatments: what is to be done?].

PMID- 15150512
TI  - [Gastrointestinal hemorrhage. Which indications for endoscopic treatments?].

PMID- 15150514
TI  - [When and how to evaluate the risk of a first variceal bleeding?].

PMID- 15150516
TI  - [How to prevent and to treat bleeding from gastric or ectopic or from portal
      hypertension gastropathy].

PMID- 15150515
TI  - [How to prevent the first variceal bleeding?].

PMID- 15150517
TI  - [Gastrointestinal hemorrhage. How to prevent rebleeding: pharmacological and
      endoscopic treatments].

PMID- 15150518
TI  - [Gastrointestinal hemorrhage. Methods of endoscopic treatment].

PMID- 15150519
TI  - [Gastrointestinal hemorrhage. Failure of pharmacological and endoscopic
      treatment: what is to be done?].

PMID- 15150520
TI  - [Gastrointestinal hemorrhage. What kind of surveillance is needed for drug
      treatment?].

PMID- 15150521
TI  - [How to treat a first episode of ascites?].

PMID- 15150522
TI  - [Treatment of refractory ascites].

PMID- 15150523
TI  - [How to treat hepatorenal syndrome].

PMID- 15150524
TI  - [How to treat and to prevent spontaneous bacterial peritonitis?].

PMID- 15150525
TI  - [Management of hepatic hydrothorax].

PMID- 15150526
TI  - [Treatment considerations for hepatopulmonary syndrome].

PMID- 15150528
TI  - [Consensus conference: complications of portal hypertension in adults (Paris,
      December 405, 2003). Short text].

PMID- 15150527
TI  - [Treatment of porto pulmonary hypertension].

PMID- 15150529
TI  - [Consensus conference: complications of portal hypertension in adults (Paris,
      December 4-5, 2003). Long text].

PMID- 15150530
TI  - An association between a functional polymorphism in the monoamine oxidase a gene
      promoter, impulsive traits and early abuse experiences.
AB  - Monoamine oxidase A (MAOA) activity is altered in mood disorders and lower
      activity associated with aggressive behavior. The gene has a functional
      polymorphism with a variable number tandem repeat (VNTR) in the upstream
      regulatory region (MAOA-uVNTR). In this study, we examined possible associations
      between the MAOA-uVNTR polymorphism and mood disorders, suicidal behavior,
      aggression/impulsivity, and effects of reported childhood abuse. In total, 663
      unrelated subjects with a psychiatric disorder and 104 healthy volunteers were
      genotyped for the 30 base pair functional VNTR. A novel repeat variation was
      identified. No statistically significant associations were found between this
      functional MAOA-uVNTR polymorphism and mood disorders or suicide attempts.
      However, the lower expression allele was associated with a history of abuse
      before 15 years of age in male subjects and with higher impulsivity in males but
      not females. Our results suggest that the lower expression of the MAOA-uVNTR
      polymorphism is related to a history of early abuse and may sensitize males, but
      not females, to the effects of early abuse experiences on impulsive traits in
      adulthood. The polymorphism may be a marker for impulsivity that in turn may
      contribute to the risk for abuse. This trait could then be further aggravated by
      abuse.

PMID- 15150531
TI  - Inhibition of G protein-activated inwardly rectifying K+ channels by various
      antidepressant drugs.
AB  - G protein-activated inwardly rectifying K+ channels (GIRK, also known as Kir3)
      are activated by various G protein-coupled receptors. GIRK channels play an
      important role in the inhibitory regulation of neuronal excitability in most
      brain regions and the heart rate. Modulation of GIRK channel activity may affect
      many brain functions. Here, we report the inhibitory effects of various
      antidepressants: imipramine, desipramine, amitriptyline, nortriptyline,
      clomipramine, maprotiline, and citalopram, on GIRK channels. In Xenopus oocytes
      injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, the various
      antidepressants tested, except fluvoxamine, zimelidine, and bupropion, reversibly
      reduced inward currents through the basal GIRK activity at micromolar
      concentrations. The inhibitions were concentration-dependent with various degrees
      of potency and effectiveness, but voltage- and time-independent. In contrast,
      Kir1.1 and Kir2.1 channels in other Kir channel subfamilies were insensitive to
      all of the drugs. Furthermore, GIRK current responses activated by the cloned A1
      adenosine receptor were similarly inhibited by the tricyclic antidepressant
      desipramine. The inhibitory effects of desipramine were not observed when
      desipramine was applied intracellularly, and were not affected by extracellular
      pH, which changed the proportion of the uncharged to protonated desipramine,
      suggesting its action from the extracellular side. The GIRK currents induced by
      ethanol were also attenuated in the presence of desipramine. Our results suggest
      that inhibition of GIRK channels by the tricyclic antidepressants and maprotiline
      may contribute to some of the therapeutic effects and adverse side effects,
      especially seizures and atrial arrhythmias in overdose, observed in clinical
      practice.

PMID- 15150532
TI  - The neurotensin agonist PD149163 increases Fos expression in the prefrontal
      cortex of the rat.
AB  - Dopaminergic axons innervating the prefrontal cortex (PFC) target both pyramidal
      cells and GABAergic interneurons. Many of these dopamine (DA) axons in the rat
      coexpress the peptide neurotransmitter neurotensin. Previous electrophysiological
      data have suggested that neurotensin activates GABAergic interneurons in the PFC.
      Activation of D2-like DA receptors increases extracellular GABA levels in the
      PFC, as opposed to the striatum, where D2 receptor activation inhibits GABAergic
      neurons. Because activation of presynaptic D2 release-modulating autoreceptors in
      the PFC suppresses DA release but increases release of the cotransmitter
      neurotensin, D2 agonists may enhance the activity of GABAergic interneurons via
      release of neurotensin. In order to determine if neurotensin can activate
      GABAergic interneurons, we treated rats with the peptide neurotensin agonist,
      PD149163, and examined Fos expression in PFC neurons. Systemic administration of
      PD149163 increased overall Fos expression in the PFC, but not in the dorsal
      striatum. PD149163 induced Fos in PFC interneurons, as defined by the presence of
      calcium-binding proteins, and in pyramidal cells. Pretreatment with the high
      affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos
      expression. These data suggest that neurotensin activates interneurons in the PFC
      of the rat.

PMID- 15150533
TI  - Rapid synaptic plasticity of glutamatergic synapses on dopamine neurons in the
      ventral tegmental area in response to acute amphetamine injection.
AB  - Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and
      it has been hypothesized that drug exposure triggers synaptic plasticity of
      glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area.
      Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to
      potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR
      ratio. We tested the prediction that an increase in GluR1-containing AMPA
      receptors would result in an increase in GluR1 homomeric receptors at synapses,
      but were unable to observe any evidence of the predicted rectification in DA
      neurons from animals treated with amphetamine. We also examined the possibility
      of increased AMPA receptor insertion in the membrane, but did not detect a
      significant increase in biotinylated surface GluR1. We conclude that amphetamine
      induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that
      potentiation of glutamatergic synapses is a relatively early event in the series
      of neuroadaptations in response to drugs of abuse.

PMID- 15150535
TI  - Modelling exposure to disinfection by-products in drinking water for an
      epidemiological study of adverse birth outcomes.
AB  - We are conducting an epidemiological study on the association between
      disinfection by-product concentrations in drinking water and adverse birth
      outcomes in the UK, using trihalomethane (THM) concentrations over defined water
      zones as an exposure index. Here we construct statistical models using sparse
      routinely collected THMs measurements to obtain quarterly estimates of mean THM
      concentrations for each water zone. We modelled the THM measurements using a
      Bayesian hierarchical mixture model, taking into account heterogeneity in THM
      concentrations between water originating from different source types, quarterly
      variation in THM concentrations and uncertainty in the true value of undetected
      and rounded measurements. Quarterly estimates of mean THM concentrations plus
      estimates of the water source type (ground, lowland surface or upland surface)
      were obtained for each water zone. THM concentration estimates were typically
      highest from July to September (third quarter), and varied considerably between
      water sources. Our exposure estimates were categorized into 'low', 'medium' and
      'high' THM classes. Our modelled quarterly exposure estimates were compared to a
      simple alternative: annual means of the raw data for each water zone. In all, 15
      25% of exposure estimates were classified differently. The modelled THM estimates
      led to slightly stronger and more precise estimates of association with risk of
      still birth and low birth weight than did the raw annual means. We conclude that
      our modelling approach enabled us to provide robust quarterly estimates of
      ecological exposure to THMs in a situation where the raw data were too sparse to
      base exposure assessment on empirical summaries alone.

PMID- 15150534
TI  - Nicotine and cotinine in adults' urine: The German Environmental Survey 1998.
AB  - In 1998, the German Environmental Survey (GerES III) recruited approximately 5000
      adults between the ages of 18 and 69 years. The study population for these
      analyses consisted of 1580 smokers (34% of the total population) and 3126
      nonsmokers. Nicotine and cotinine concentrations in urine were determined by HPLC
      methods with UV-detection and corrected for creatinine. Nicotine and cotinine
      concentrations differed between smokers and nonsmokers by factors of 10-100. The
      multiple linear regression models used for the analyses of nicotine detection in
      the urine of smokers explained 43.2% and 42.3% of the total volume-specific and
      creatinine-specific variances, respectively. Cigarette smoking was the major
      factor responsible for 41% of the total variance. The explained variances of the
      cotinine results were larger, 51.0% and 49.3% of the total variance were volume
      specific and creatinine-specific, respectively. More than 20% of nonsmokers in
      GerES III were exposed to environmental tobacco smoke at home, at work or in
      other places. The logistic regression analysis approach used for the group of
      nonsmokers showed the greatest effects for those exposed to tobacco smoke at home
      (adjusted OR varied between 4 and 6). These results were seen for nicotine as
      well as for cotinine excretion. Exposure to tobacco smoke in the workplace
      doubled the risk for the detection of nicotine and cotinine in urine. When other
      risk factors such as age, sex, social status, community size, season of urine
      collection, and the consumption of food containing nicotine such as potatoes,
      cabbage, tea were included, the effect estimates for tobacco smoke exposure
      remained unchanged. A new federal bill to diminish environmental tobacco smoke
      (ETS) exposure in the workplace was recently passed in Germany, but protection of
      nonsmokers from smoking family members at home needs more attention.

PMID- 15150536
TI  - Chronic arsenic exposure and urinary 8-hydroxy-2'-deoxyguanosine in an arsenic
      affected area in Inner Mongolia, China.
AB  - OBJECTIVE: Recent studies have shown that generation of reactive oxidants during
      arsenic metabolism can play an important role in arsenic-induced injury. The
      purpose of this study was to examine the relationship between arsenic in drinking
      water and oxidative stress in humans by measuring 8-Hydroxy-2'-deoxyguanosine (8
      OHdG). METHODS: We performed a cross-sectional study in an arsenic-affected
      village in Hetao Plain, Inner Mongolia, China. A total of 134 of the 143
      inhabitants (93.7%) of the village participated in the study. The levels of 8
      OHdG, arsenic and its metabolites were measured in urine collected from the
      participants. Regression analyses were performed to investigate the relationship
      between arsenic species and 8-OHdG levels in urine. RESULTS: In the polluted
      village, monomethylarsenic was significantly higher in subjects with arsenic
      dermatosis than those without dermatosis despite no difference in mean levels of
      arsenic in well water between both types of subject. For subjects with arsenic
      dermatosis, arsenic species and metabolites in urine are significantly associated
      with 8-OHdG, while there was no statistically significant relationship for
      subjects without arsenic dermatosis. For all residents of the polluted village,
      the levels of dimethylarsenic and 8-OHdG were significantly higher for those who
      had been exposed to well water for more than 12 years. CONCLUSIONS: These results
      provide evidence of a link between exposure to arsenic from drinking water and
      oxidative stress, which may play an important role in arsenic-involved injuries.

PMID- 15150537
TI  - Maintenance of clonal diversity in Dipsa bifurcata (Fallen, 1810) (Diptera:
      Lonchopteridae). I. Fluctuating seasonal selection moulds long-term coexistence.
AB  - The deterministic maintenance of clonal diversity in thelytokous taxa can be seen
      as a model for understanding how environmental heterogeneity both can stabilize
      genetic diversity and can allow coexistence of competing species. We here analyze
      the temporal fluctuations in clonal diversity in the thelytokous Lonchopterid
      fly, Dipsa bifurcata (Fallen, 1810), at four localities in Sweden over an 8-year
      period. Estimated fitness values for clones are cyclical, synchronous among
      populations and correlated with seasonal changes in the environment. Differential
      winter viability and emergence from overwintering along with differential
      reproductive rate during the summer appear to be the selective mechanisms by
      which long-term clonal diversity is maintained. In a companion paper (Tomiuk et
      al, 2004), we present a model for the maintenance of clonal diversity through the
      mechanism of differential diapause among clones, utilizing fitness values
      estimated from the data presented here. In general, our results imply that
      fluctuating seasonal fitnesses can maintain stable genetic polymorphism within
      populations, as well as coexistence between closely related competitors, when
      coupled with differences in diapause phenology.

PMID- 15150538
TI  - Maintenance of clonal diversity in Dipsa bifurcata (Fallen, 1810) (Diptera:
      Lonchopteridae). II. Diapause stabilizes clonal coexistence.
AB  - We analyze a selection model analogous to a one-locus, two-allele haploid system
      that can explain recurrent seasonal changes in diversity for communities with
      diapausing species or populations with diapausing clones. The model demonstrates
      the potential influence of differential diapause on the stability of species and
      clonal coexistence and, by extension, on the maintenance of genetic polymorphism
      in general. Using estimates of clonal fitness values from populations of the
      parthenogenetic spear-winged fly Dipsa bifurcata (Fallen, 1810) (Diptera:
      Lonchopteridae), the model explains the long-term stable oscillation of clonal
      frequencies exhibited by these populations. In general, clones or species that
      share the same spatial habitat can persist in stable coexistence if there are
      differences not only in their temporarily fluctuating fitness values but also in
      their dormancy patterns.

PMID- 15150539
TI  - Analysis of genetic diversity and conservation priorities in Iberian pigs based
      on microsatellite markers.
AB  - The Iberian breed is the most important pig population of the Mediterranean type.
      The genetic structure of two strains (Torbiscal and Guadyerbas) and three
      varieties (Retinto, Entrepelado and Lampino) of this breed was studied using 173
      pigs genotyped for 36 microsatellites. In addition, 40 pigs of the related Duroc
      breed were also analysed. In the 1960s, the Iberian breed's numbers were severely
      reduced by disease, due to economic change and to crossbreeding. Varieties are in
      danger of disappearance or blending. A new conservation strategy is required. An
      analysis was performed that allows us to ascertain the loss or gain of genetic
      diversity if one or several subpopulations are removed. The results are compared
      with those using the Weitzman method. The two methodologies produce conservation
      priorities that are completely different, the reason being that the Weitzman
      method does not take into account the within-population genetic diversity. We
      apply optimal contribution theory and a new procedure for cluster analysis, and
      discuss their value in the general framework of the problems of setting of
      priorities and tactics for the conservation of genetic resources.

PMID- 15150540
TI  - Microsatellite DNA variation reveals high gene flow and panmictic populations in
      the Adriatic shared stocks of the European squid and cuttlefish (Cephalopoda).
AB  - In the semienclosed Adriatic Sea, the shared stocks of the cephalopods Loligo
      vulgaris and Sepia officinalis represent important marine fisheries resources
      exploited by all coastal countries. The improving of knowledge on the demographic
      features of these shared stocks is internationally relevant for adopting
      responsible management and conservation of these marine resources. Analyses of
      microsatellite variation in geographical samples collected from all parts of the
      Adriatic Sea were performed using arrays of species-specific di-nucleotide and
      tri-nucleotide loci. In L. vulgaris the level of genetic variability was
      consistent with that observed in other loliginid species, whereas the S.
      officinalis stock showed a microsatellite variation markedly lower than that
      estimated for the Atlantic and Mediterranean populations collected around the
      Iberian peninsula. The weak spatial genetic differentiation, the discordant
      results of the genetic divergence estimators and the lack of any geographical
      cline in the spatial genetic differences suggest the occurrence of single
      genetically homogeneous populations within the Adriatic stocks of both species,
      recommending a coordinated management of the squid and cuttlefish by the Adriatic
      fishing countries. On the contrary, significant differences detected in temporal
      replicates of S. officinalis might suggest that allelic frequency can change
      relating to reproductive behaviour.

PMID- 15150541
TI  - Refined genotype-phenotype correlations in cases of chromosome 6p deletion
      syndromes.
AB  - Clinical reports of cases with deletions in chromosome 6p are relatively rare. We
      present a detailed study by fluorescent in situ hybridisation (FISH) of six new
      cases with distinct but overlapping 6p deletions involving the 6p24-pter
      chromosomal segment. Chromosomal breakpoints in individual cases were
      investigated using a large panel of probes previously mapped and characterised in
      our laboratory to cover the distal region of 6p. These cases have allowed
      refinement of genotype-phenotype correlations and strongly suggest a gene
      involved in regulating the development of hearing is localised within 6p25. There
      is also evidence for one or more loci involved in heart, skeletal and
      craniofacial development in the 6p24-p25 region. Furthermore, the Dandy-Walker
      malformation is associated with deletion of 6p24-pter.

PMID- 15150542
TI  - p53 can inhibit cell proliferation through caspase-mediated cleavage of
      ERK2/MAPK.
AB  - Stimulation of the Ras/MAPK cascade can either activate p53 and promote
      replicative senescence and apoptosis, or degrade p53 and promote cell survival.
      Here we show that p53 can directly counteract the Ras/MAPK signaling by
      inactivating ERK2/MAPK. This inactivation is due to a caspase cleavage of the
      ERK2 protein and contributes to p53-mediated growth arrest. We found that in Ras
      transformed cells, growth arrest induced by p53, but not p21(Waf1), is associated
      with a strong reduction in ERK2 activity, phosphorylation, and protein half-life,
      and with the appearance of caspase activity. Likewise, DNA damage-induced cell
      cycle arrest correlates with p53-dependent ERK2 downregulation and caspase
      activation. Furthermore, caspase inhibitors or expression of a caspase-resistant
      ERK2 mutant interfere with ERK2 cleavage and restore proliferation in the
      presence of p53 activation, indicating that caspase-mediated ERK2 degradation
      contributes to p53-induced growth arrest. These findings strongly point to ERK2
      as a novel p53 target in growth suppression.

PMID- 15150543
TI  - DNA damage induces the rapid and selective degradation of the DeltaNp73 isoform,
      allowing apoptosis to occur.

PMID- 15150548
TI  - Is there a role for chemotherapy in prostate cancer?
AB  - There is evidence from randomised-controlled trials that patients with
      symptomatic hormone-refractory prostate cancer may experience palliative benefit
      from chemotherapy with mitoxantrone and prednisone. This treatment is well
      tolerated, even by elderly patients, although the cumulative dose of mitoxantrone
      is limited by cardiotoxicity. Treatment with docetaxel or paclitaxel, with or
      without estramustine, appears to convey higher rates of prostate-specific antigen
      response in phase II trials, but is more toxic. Large phase III trials comparing
      docetaxel with mitoxantrone have completed accrual. There is no role for
      chemotherapy in earlier stages of disease except in the context of a well
      designed clinical trial.

PMID- 15150549
TI  - Bladder cancer: worse survival in women from deprived areas.
AB  - In a case-note review of 120 women and 227 men presenting with muscle-invasive
      bladder tumours in 1998, survival was worse for women in 3 years of follow-up,
      with the greatest difference, of 19.9%, at 6 months. For more deprived women, 6
      month survival was 52.3%, and 32 (37.2%) presented with advanced disease,
      compared with 73.5%, and three (8.8%) for less deprived women.

PMID- 15150550
TI  - Modulation of thymidine phosphorylase by neoadjuvant chemotherapy in primary
      breast cancer.
AB  - The combination effect of docetaxel and capecitabine on tumour response rate and
      survival was demonstrated recently in metastatic breast cancer patients. This
      combination was based on an experimental hypothesis that taxane can increase
      tumour sensitivity to the effect of capecitabine through the upregulation of
      thymidine phosphorylase (TP), which is responsible for the metabolism of 5
      fluorouracil (5-FU) and its derivatives, including capecitabine. To examine the
      alteration in TP expression before and after neoadjuvant chemotherapy, 92
      patients with primary breast cancer (T2-4N0-1M0) were enrolled in this study; 14
      were treated with adriamycin and cyclophosphamide (AC) or epirubicin and
      cyclophosphamide (EC); 58 with 5-FU, adriamycin, and cyclophosphamide (FAC) or 5
      FU, epirubicin, and cyclophosphamide (FEC); and 20 with FEC followed by
      docetaxel/taxotere (TXT-containing regimen). Thymidine phosphorylase upregulation
      was seen in 54.4% and 32.6% of patients in tumour cells and stromal cells,
      respectively. Increases in TP expression were found only in the AC/EC and TXT
      containing regimen groups. In conclusion, it was strongly suggested that unlike 5
      FU-containing regimens, the taxane and AC combination therapies upregulate TP
      expression in primary breast cancer. Thymidine phosphorylase upregulation by
      several anticancer drugs implies the importance of individualised strategies for
      sensitisation of tumour tissues to 5-FU and its derivatives.

PMID- 15150551
TI  - Evaluation of the response to treatment of solid tumours - a consensus statement
      of the International Cancer Imaging Society.
AB  - New guidelines to evaluate the response to treatment in solid tumors using
      imaging techniques have major limitations and important implications for
      radiological workload. This consensus statement from the International Cancer
      Imaging Society (ICIS) reviews the RECIST criteria and addresses several
      challenges regarding tumour measurement. Recommendations are made regarding
      tumour measurement and other issues are raised. The growing need to introduce a
      multimodality approach to monitoring response is recognized. ICIS welcomes a
      dialogue with the authors of RECIST to address issues raised in this review.

PMID- 15150553
TI  - Absence of human T-cell lymphotropic virus type I and human foamy virus in
      thymoma.
AB  - The cause of thymoma, a rare malignancy of thymic epithelial cells, is unknown.
      Recent studies have reported the detection of DNA from human T-cell lymphotropic
      virus type I (HTLV-I) and human foamy virus (HFV) in small numbers of thymoma
      tumours, suggesting an aetiologic role for these retroviruses. In the present
      study, we evaluated 21 US thymoma patients and 20 patients with other cancers for
      evidence of infection with these viruses. We used the polymerase chain reaction
      to attempt to amplify viral DNA from tumour tissues, using primers from the pol
      and tax (HTLV-I) and gag and bel1 (HFV) regions. In these experiments, we did not
      detect HTLV-I or HFV DNA sequences in any thymoma or control tissues, despite
      adequate sensitivity of our assays (one HTLV-I copy per 25 000 cells, one HFV
      copy per 7500 cells). Additionally, none of 14 thymoma patients evaluated
      serologically for HTLV I/II infection was positive by enzyme-linked immunoassay
      (ELISA), while five (36%) had indeterminate Western blot reactivity. In
      comparison, one of 20 US blood donors was HTLV-I/II ELISA positive, and nine
      (45%) donors, including the ELISA-positive donor, had indeterminate Western blot
      reactivity. Western blot patterns varied across individuals and consisted mostly
      of weak reactivity. In conclusion, we did not find evidence for the presence of
      HTLV-I or HFV in US thymoma patients.

PMID- 15150552
TI  - Low-dose interferon-gamma-producing human neuroblastoma cells show reduced
      proliferation and delayed tumorigenicity.
AB  - Interferon-gamma (IFN-gamma) directs T helper-1 cell differentiation and mediates
      antitumour effects in preclinical models. However, high-dose IFN-gamma is toxic
      in vivo, and IFN-gamma-transfected neuroblastoma (NB) cells secreting high
      amounts of the cytokine may be lost due to cell apoptosis or differentiation. Two
      human NB cell lines (ACN and SK-N-BE2(c)) differing as to genetic and phenotypic
      features were transfected with the human IFN-gamma gene and selected on the
      grounds of the low concentrations of IFN-gamma produced. In both IFN-gamma
      transfected cell lines, autocrine and paracrine activation of IFN-gamma-mediated
      pathways occurred, leading to markedly reduced proliferation rate, to increased
      expression of surface HLA and CD40 molecules and of functional TNF binding sites.
      ACN/IFN-gamma cells showed a significantly delayed tumorigenicity in nude mice as
      compared to parental cells. ACN/IFN-gamma tumours were smaller, with extensive
      necrotic area as a result of a damaged and defective microvascular network. In
      addition, a significant reduction in the proliferation index was observed. This
      is the first demonstration that IFN-gamma inhibits in vivo proliferation of NB
      cell by acting on the tumour cell itself. This effect adds to the
      immunoregulatory and antiangiogenic activities operated by IFN-gamma in syngeneic
      tumour-bearing hosts.

PMID- 15150554
TI  - Phase II study of docetaxel in combination with epirubicin and protracted venous
      infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast
      cancer. A Yorkshire breast cancer research group study.
AB  - This study was originally designed as a phase I/II study, with a dose escalation
      of docetaxel in combination with epirubicin 50 mg m(-2) and 5-fluorouracil (5-FU)
      200 mg m(-2) day(-1). However, as dose escalation was not possible, the study is
      reported as a phase II study of the combination to assess response and toxicity.
      A total of 51 patients with locally advanced or metastatic breast cancer were
      treated on this phase II study, with doses of docetaxel 50 mg m(-2), epirubicin
      50 mg m(-2) and infusional 5-FU 200 mg m(-2) day(-1) for 21 days. The main
      toxicity of this combination was neutropenia with 89% of patients having grade 3
      and 4 neutropenia, and 39% of patients experiencing febrile neutropenia.
      Nonhaematological toxicity was mild. The overall response rate in the assessable
      patients was 64%, with median progression-free survival of 38 weeks, and median
      survival of 70 weeks. The ETF regimen was found to be toxic, and it was not
      possible to escalate the dose of docetaxel above the first dose level. This
      regimen has therefore not been taken any further, but as a development of this a
      new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and
      capecitabine, days 1-14.

PMID- 15150555
TI  - Alteration of the copy number and deletion of mitochondrial DNA in human
      hepatocellular carcinoma.
AB  - Somatic mutations in mitochondrial DNA (mtDNA) have been detected in
      hepatocellular carcinoma (HCC). However, it remains unclear whether mtDNA copy
      number and mitochondrial biogenesis are altered in HCC. In this study, we found
      that mtDNA copy number and the content of mitochondrial respiratory proteins were
      reduced in HCCs as compared with the corresponding non-tumorous livers. MtDNA
      copy number was significantly reduced in female HCC but not in male HCC.
      Expression of the peroxisome proliferator-activated receptor gamma coactivator-1
      was significantly repressed in HCCs (P<0.005), while the expression of the
      mitochondrial single-strand DNA-binding protein was upregulated, indicating that
      the regulation of mitochondria biogenesis is disturbed in HCC. Moreover, 22% of
      HCCs carried a somatic mutation in the mtDNA D-loop region. The non-tumorous
      liver of the HCC patients with a long-term alcohol-drinking history contained
      reduced mtDNA copy number (P<0.05) and higher level of the 4977 bp-deleted mtDNA
      (P<0.05) as compared with non-alcohol patients. Our results suggest that reduced
      mtDNA copy number, impaired mitochondrial biogenesis and somatic mutations in
      mtDNA are important events during carcinogenesis of HCC, and the differential
      alterations in mtDNA of male and female HCC may contribute to the differences in
      the clinical manifestation between female and male HCC patients.

PMID- 15150556
TI  - New technologies in screening for breast cancer: a systematic review of their
      accuracy.
AB  - We systematically reviewed the literature on the accuracy of new technologies
      proposed for breast cancer screening. Four potential tests were identified
      (ultrasound, magnetic resonance imaging (MRI), full-field digital mammography
      (FFDM), and computer-aided detection (CAD)) for which primary studies met quality
      and applicability criteria and provided adequate data on test accuracy. These
      technologies have been assessed in cross-sectional studies of test accuracy where
      the new test is compared to mammography. Ultrasound, used as an adjunct to
      mammography in women with radiologically dense breasts, detects additional
      cancers and causes additional false positives. Magnetic resonance imaging may
      have a better sensitivity (but lower specificity) than mammography in selected
      high-risk women, but studies of this technology included small number of cancers.
      Computer-aided detection may enhance the sensitivity of mammography and warrants
      further evaluation in large prospective trials. One study of FFDM suggests that
      it may identify some cancers not identified on conventional mammography and may
      result in a lower recall rate. The evidence is currently insufficient to support
      the use of any of these new technologies in population screening, but would
      support further evaluation.

PMID- 15150557
TI  - Predictors of patients' choices for breast-conserving therapy or mastectomy: a
      prospective study.
AB  - A study was undertaken to describe the treatment preferences and choices of
      patients with breast cancer, and to identify predictors of undergoing breast
      conserving therapy (BCT) or mastectomy (MT). Consecutive patients with stage I/II
      breast cancer were eligible. Information about predictor variables, including
      socio-demographics, quality of life, patients' concerns, decision style,
      decisional conflict and perceived preference of the surgeon was collected at
      baseline, before decision making and surgery. Patients received standard
      information (n=88) or a decision aid (n=92) as a supplement to support decision
      making. A total of 180 patients participated in the study. In all, 72% decided to
      have BCT (n=123); 28% chose MT (n=49). Multivariate analysis showed that what
      patients perceived to be their surgeons' preference and the patients' concerns
      regarding breast loss and local tumour recurrence were the strongest predictors
      of treatment preference. Treatment preferences in itself were highly predictive
      of the treatment decision. The decision aid did not influence treatment choice.
      The results of this study demonstrate that patients' concerns and their
      perceptions of the treatment preferences of the physicians are important factors
      in patients' decision making. Adequate information and communication are
      essential to base treatment decisions on realistic concerns, and the treatment
      preferences of patients.

PMID- 15150558
TI  - Repair of UV-induced thymine dimers is compromised in cells expressing the E6
      protein from human papillomaviruses types 5 and 18.
AB  - Ultraviolet (UV) irradiation is a major mutagenic environmental agent, causing
      the appearance of DNA adducts that, if unrepaired, may give rise to mutations.
      Ultraviolet radiation has been indicated as a major risk factor in the
      development of nonmelanoma skin cancers; however, recent reports have suggested
      that infections with human papillomaviruses, a widespread family of
      epitheliotropic DNA viruses, may also contribute to the tumorigenic process.
      Here, we investigated whether expression of the E6 protein from different HPV
      types interfere with the repair of thymine dimers caused by UV-B radiation.
      Results show that unrepaired DNA damage can be observed in UV-B-irradiated cells
      expressing the E6 protein of HPV types found in cervical and epithelial cancers.
      Moreover, such cells have the ability to overcome the G(1) cell cycle checkpoint
      induced as a result of unrepaired DNA.

PMID- 15150560
TI  - Breast cancer risk among first-generation migrants in the Netherlands.
AB  - We investigated breast cancer incidence in migrants in the Netherlands in 1988
      1998. The standardised incidence ratio for breast cancer in Northwest-Netherlands
      was statistically significantly reduced for women born in Surinam (0.56), Turkey
      (0.29) and Morocco (0.22). The proportion of women with advanced stages (III and
      IV) did not differ significantly between migrants and women born in the
      Netherlands.

PMID- 15150559
TI  - Cytomegalovirus, Epstein-Barr virus and risk of breast cancer before age 40
      years: a case-control study.
AB  - We investigated whether there is an association between cytomegalovirus (CMV) and
      Epstein-Barr virus (EBV) IgG levels and risk of breast cancer before age 40
      years. CMV and EBV IgG levels were measured in stored plasma from 208 women with
      breast cancer and 169 controls who participated in the Australian Breast Cancer
      Family Study (ABCFS), a population-based case-control study. CMV and EBV IgG
      values were measured in units of optical density (OD). Cases and controls did not
      differ in seropositivity for CMV (59 and 57% respectively; P=0.8) or EBV (97 and
      96% respectively; P=0.7). In seropositive women, mean IgG values were higher in
      cases than controls for CMV (1.20 vs 0.98 OD, P=0.005) but not for EBV (2.65 vs
      2.57 OD, P=0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06
      2.03) for CMV IgG and 1.11 (0.93-1.33) for EBV IgG. The higher mean CMV IgG
      levels found in women with breast cancer could be the result of a more recent
      infection with CMV, and may mean that late exposure to CMV is a risk factor for
      breast cancer.

PMID- 15150561
TI  - Exercise activity, body size and premenopausal breast cancer survival.
AB  - We evaluated prediagnosis predictors of breast cancer survival among 717
      premenopausal breast cancer patients enrolled in a population-based case-control
      study and followed for 10.4 years. Using Cox's proportional hazards models,
      lifetime exercise, weight, and height were not associated with survival. Higher
      body mass index (trend P=0.21) and recent exercise activity (trend P=0.31) were
      weakly associated with longer survival.

PMID- 15150562
TI  - Late resistance to imatinib therapy in a metastatic gastrointestinal stromal
      tumour is associated with a second KIT mutation.
AB  - Currently, there are no data on the secondary resistance of gastrointestinal
      stromal tumours to imatinib. Here, we report a case of metastatic
      gastrointestinal stromal tumour that relapsed during imatinib therapy. Mutation
      analysis showed that the imatinib-resistant liver tumour contained two c-kit
      mutations.

PMID- 15150563
TI  - AUC of Calvert's formula in targeted intra-arterial carboplatin chemoradiotherapy
      for cancer of the oral cavity.
AB  - We investigated whether intra-arterial administration of carboplatin using
      Calvert's formula is useful for avoiding thrombocytopenia in targeted
      chemoradiotherapy in patients with squamous cell cancer of the oral cavity and
      oropharynx. Carboplatin was infused intra-arterially under digital subtraction
      angiography in 28 patients. In the first group of patients, the dose of
      carboplatin was calculated according to the body surface area (BS group). In the
      second group, the dose was calculated using Calvert's formula (AUC group). The
      value for AUC (area under concentration vs time curve; mg ml(-1) min(-1)) in the
      formula was set at 4.5. All patients received concurrent radiotherapy (30 Gy) and
      were given oral tegafur-uracil (UFT((R)), 400-600 mg day(-1)). The AUC group
      showed a significantly lower percentage platelet reduction than the BS group
      (49.0+/-22.0 vs 65.1+/-23.2%; P=0.045) and also tended to have a higher platelet
      nadir count (10.9+/-4.2 vs 8.4+/-5.8 x 10(4); P=0.27) without reducing the
      antitumour effect. The value of 4.5 for target AUC is recommended clinically.
      However, AUC of Calvert's formula could not predict thrombocytopenia associated
      with intra-arterial chemoradiotherapy due to the variability of the actual AUC.

PMID- 15150564
TI  - Combination phase I study of nedaplatin and gemcitabine for advanced non-small
      cell lung cancer.
AB  - To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with
      gemcitabine, and to observe their antitumour activity, we conducted a combination
      phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received
      nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and
      gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8,
      every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC
      who received no prior chemotherapy or one previous chemotherapy regimen were
      enrolled. The most frequent toxicities were neutropenia and thrombocytopenia;
      nonhaematological toxicities were generally mild. Three out of six patients
      experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed
      anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine,
      which was regarded as the MTD. There were three partial responses, for an overall
      response rate of 16.7%. The median survival time and 1-year survival rate were
      9.1 months and 34.1%, respectively. This combination is well tolerated and active
      for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg
      m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and
      further evaluation in prospective randomised trials with cisplatin- or
      carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.

PMID- 15150565
TI  - Role of natriuretic peptides in the diagnosis and treatment of patients with
      carcinoid heart disease.
AB  - Carcinoid heart disease (CHD) occurs in 20-70% of the patients with metastatic
      well-differentiated neuroendocrine tumours (NET). We evaluated whether
      natriuretic peptides (ANP or NT-proBNP) are useful in early detection of CHD.
      Blood samples from 32 patients with NET were compared with cardiac ultrasound
      follow-up. CHD was defined as thickening of the tricuspid valve in the presence
      of grade III-IV/IV tricuspid valve regurgitation. CHD was found in nine out of 32
      patients (28%), all with symptoms of the carcinoid syndrome compared to 65% in
      the 23 patients without CHD (P=0.04). Median levels of NT-proBNP and 5-HIAA were
      significantly higher in patients with CHD (894 ng l(-1) and 815 micromol 24 h(
      1)) compared to those without (89 and 206 ng l(-1), P<0.001 and P=0.007). No
      significant differences were detected in ANP levels (P=0.11). Dilatation of the
      right atrium and ventricle as well as thickening of the tricuspid valve and
      degree of regurgitation were statistically significant correlated with NT-proBNP
      levels. The accuracy of NT-proBNP in the diagnosis of CHD was higher than that of
      ANP. A significantly better survival was observed in case of normal NT-proBNP
      values. In conclusion, NT-proBNP is helpful as a simple marker in the diagnosis
      of CHD. Survival is better in patients with normal levels of NT-proBNP.

PMID- 15150566
TI  - Cost study of metal stent placement vs single-dose brachytherapy in the
      palliative treatment of oesophageal cancer.
AB  - Self-expanding metal stent placement and single-dose brachytherapy are commonly
      used for the palliation of oesophageal obstruction due to inoperable
      oesophagogastric cancer. We randomised 209 patients to the placement of an
      Ultraflex stent (n=108) or single-dose brachytherapy (12 Gy, n=101). Cost
      comparisons included comprehensive data of hospital costs, diagnostic
      interventions and extramural care. We acquired detailed information on health
      care consumption from a case record form and from monthly home visits by a
      specialised nurse. The initial costs of stent placement were higher than the
      costs of brachytherapy (1500 euro vs 570 euro; P<0.001). Total medical costs
      were, however, similar (stent 11 195 euro vs brachytherapy 10 078 euro, P>0.20).
      Total hospital stay during follow-up was 11.5 days after stent placement vs 12.4
      days after brachytherapy, which was responsible for the high intramural costs in
      both treatment groups (stent 6512 euro vs brachytherapy 7982 euro, P>0.20). Costs
      for medical procedures during follow-up were higher after stent placement (stent
      249 euro vs brachytherapy 168 euro, P=0.002), while the costs of extramural care
      were similar (1278 euro vs 1046 euro, P>0.20). In conclusion, there are only
      small differences between the total medical costs of both palliative treatment
      modalities, despite the fact that the initial costs of stent placement are much
      higher than those of brachytherapy. Therefore, cost considerations should not
      play an important role in decision making on the appropriate palliative treatment
      strategy for patients with malignant dysphagia.

PMID- 15150567
TI  - CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of
      a meta-analysis in 2063 patients.
AB  - The purpose of this study was to determine the prognostic significance of a high
      pretreatment serum CYFRA 21-1 level (a cytokeratin 19 fragment) adjusted for the
      effects of well-known co-variables in non-small-cell lung cancer (NSCLC). This
      meta-analysis based on individual updated data gathered comprehensive databases
      from published or unpublished controlled studies dealing with the prognostic
      effect of serum CYFRA 21-1 level at presentation in NSCLC of any stage (nine
      institutions, 2063 patients). Multivariate regression was carried out with the
      Cox model. The proportional hazard assumption for each of the selected variables
      retained in the final model was originally checked by log minus log plots
      baseline hazard ratio. The follow-up ranged from 25 to 78 months. A total of 1616
      events were recorded. In the multivariate analysis performed at the 1-year end
      point, a high pretreatment CYFRA 21-1 level was an unfavourable prognostic
      determinant in all centres except one (Hazard ratio (95% confidence interval):
      1.88 (1.64-2.15), P<10(-4)). Other significant variables were stage of the
      disease, age and performance status. Within the first 18 months, the procedure
      disclosed a nearly similar hazard ratio for patients having a high pretreatment
      serum CYFRA 21-1 level (1.62 (1.42-1.86), P<10(-4)). For patients who did not
      undergo surgery, the hazard ratio during the first year of follow-up was 1.78
      (1.54-2.07), P<10(-4). Finally, in the surgically treated population, at the 2
      year end point, a high pretreatment CYFRA 21-1 and a locally advanced stage
      remained unfavourable prognostic determinants. In conclusion CYFRA 21-1 might be
      regarded as a putative co-variable in analysing NSCLC outcome inasmuch as a high
      serum level is a significant determinant of poor prognosis whatever the planned
      treatment.

PMID- 15150568
TI  - HER2 expression in breast cancer primary tumours and corresponding metastases.
      Original data and literature review.
AB  - The aim of this study was to evaluate whether the HER2 expression in breast
      cancer is retained in metastases. The HER2 expression in primary tumours and the
      corresponding lymph node metastases were evaluated in parallel samples from 47
      patients. The HercepTest was used for immunohistochemical analyses of HER2
      overexpression in all cases. CISH/FISH was used for analysis of gene
      amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found
      in 55% of both the primary tumours and of the lymph node metastases. There were
      only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+
      when the metastases were compared to the corresponding primary tumours. However,
      there were no cases with drastic changes in HER2 expression between the primary
      tumours and the corresponding lymph node metastases. The literature was reviewed
      for similar investigations, and it is concluded that breast cancer lymph node
      metastases generally overexpress HER2 to the same extent as the corresponding
      primary tumours. This also seems to be the case when distant metastases are
      considered. It has been noted that not all patients with HER2 overexpression
      respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression
      is encouraging for efforts to develop complementary forms of therapy, for
      example, therapy with radionuclide-labelled Trastuzumab.

PMID- 15150569
TI  - Somatic mutations of KIT in familial testicular germ cell tumours.
AB  - Somatic mutations of the KIT gene have been reported in mast cell diseases and
      gastrointestinal stromal tumours. Recently, they have also been found in
      mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with
      bilateral disease. We screened the KIT coding sequence (except exon 1) for
      germline mutations in 240 pedigrees with two or more cases of TGCT. No germline
      mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic
      mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five
      somatic mutations were identified; four were missense amino-acid substitutions in
      exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from
      cases with bilateral disease carried KIT mutations compared with three out of 116
      unilateral cases (P=0.026). The results indicate that somatic KIT mutations are
      implicated in the development of a minority of familial as well as sporadic TGCT.
      They also lend support to the hypothesis that KIT mutations primarily take place
      during embryogenesis such that primordial germ cells with KIT mutations are
      distributed to both testes.

PMID- 15150570
TI  - Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone
      acetate (CB7630) in patients with prostate cancer.
AB  - A series of three dose escalating studies were conducted to investigate the
      ability of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate,
      to cause maximum suppression of testosterone synthesis when delivered to castrate
      and noncastrate males with prostate cancer. Study A was a single dose study in
      castrate males. Study B was a single dose study in noncastrate males and study C
      was a multiple dose study in noncastrate males. The drug was given orally in a
      once-daily dose and blood samples taken to assess pharmacokinetic (PK) parameters
      and hormone levels in all patients. The study drug was well tolerated with some
      variability in PKs. Suppression of testosterone levels to <0.14 nmol l(-1) was
      seen in four out of six castrate males treated with a single dose of 500 mg. At
      800 mg given days 1-12 in noncastrate males, target suppression was achieved in
      three out of three patients, but a two- to three-fold increase of Luteinising
      Hormone (LH) levels in two out of three patients overcame suppression within 3
      days. All patients in the multiple dose study developed an abnormal response to a
      short Synacthen test by day 11, although baseline cortisol levels remained
      normal. This is the first report of the use of a specific 17alpha
      hydroxylase/(17,20)-lyase inhibitor in humans. Repeated treatment of men with
      intact gonadal function with abiraterone acetate at a dose of 800 mg can
      successfully suppress testosterone levels to the castrate range. However, this
      level of suppression may not be sustained in all patients due to compensatory
      hypersecretion of LH. The enhanced testosterone suppression achieved in castrate
      men merits further clinical study as a second-line hormonal treatment for
      prostate cancer. Adrenocortical suppression may necessitate concomitant
      administration of replacement glucocorticoid.

PMID- 15150571
TI  - Normal expression of DNA repair proteins, hMre11, Rad50 and Rad51 but protracted
      formation of Rad50 containing foci in X-irradiated skin fibroblasts from
      radiosensitive cancer patients.
AB  - About 5% of oncology patients treated by radiation therapy develop acute or late
      radiotoxic effects whose molecular mechanisms remain poorly understood. In this
      study, we evaluated the potential role of DNA repair proteins in the
      hypersensitivity of cancer patients to radiation therapy. The expression levels
      and focal nuclear distribution of DNA repair proteins, hMre11, Rad50 and Rad51
      were investigated in skin fibroblasts strains derived from cancer patients with
      adverse early skin reaction to radiotherapy using Western blot and foci
      immunofluorescence techniques, respectively. Cells from cancer patients with
      normal reaction to radiotherapy as well as cells from apparently healthy subjects
      served as controls. Cellular radiosensitivity after in vitro irradiation was
      assessed by the clonogenic survival assay. The clonogenic survival assay and
      Western blot analysis of the DNA repair proteins did not reveal any abnormalities
      in cellular radiosensitivity in vitro and in protein expression levels or their
      migration patterns in the fibroblasts derived from cancer patients with
      hypersensitive reaction to radiotherapy. In contrast, in vitro irradiated cells
      from radiosensitive patients exhibited a significantly higher number of nuclei
      with focally concentrated Rad50 protein than in both control groups. The observed
      alteration of the distribution of radiation-induced Rad50 foci in cells derived
      from cancer patients with acute side reactions to radiotherapy might contribute
      to their radiation therapy outcome. These data suggest the usefulness of the
      Rad50 foci analysis for predicting clinical response of cancer patients to
      radiotherapy.

PMID- 15150572
TI  - Molecular alterations in apoptotic pathways after PKB/Akt-mediated
      chemoresistance in NCI H460 cells.
AB  - Protein kinase B/Akt has been described as a central mediator of antiapoptotic
      signals in cancer cells. Furthermore, Akt has been shown to affect cell cycle
      progression and proliferative pathways and to possess a potential function in
      tumorigenesis and chemoresistance. In this study, we show that the ectopic
      expression of a constitutively active form of Akt1 (CA-Akt1) results in enhanced
      chemoresistance of NCI H460 human NSCLC cells towards a panel of chemotherapeutic
      agents. To understand the molecular alterations leading to impaired
      chemosensitivity mediated by activated Akt, we analysed various apoptotic
      pathways, including the activation of p53, caspases 3, 7, 8, and 9, release of
      cytochrome c from mitochondria, and the expression levels of pro- and
      antiapoptotic proteins such as Bcl-2, Bcl-x(L), Bcl-x(s), Bax, or Bfl-1. We
      observed that expression of CA-Akt did not interfere with single defined
      apoptotic switches, but modulated the apoptotic threshold of several apoptotic
      pathways towards increasing the threshold of onset. In particular, we found that
      CA-Akt-expressing cells displayed increased expression of the antiapoptotic Bcl-2
      family member protein Bcl-x(l), and a delayed onset of the p53 pathway after
      treatment with cisplatin or Mitoxantrone. Thus, our data suggest that Akt
      mediates chemoresistance in NHI H460 cells by interfering with and delaying the
      onset of various apoptotic pathways. A complete inactivation of apoptotic
      pathways was observed in none of the molecular alterations investigated. Our data
      strengthen the role of Akt as a central mediator of cell survival signals and/or
      chemoresistance and as an attractive target for cancer cell chemosensitisation.

PMID- 15150573
TI  - Clinical evaluation of atypical glandular cells of undetermined significance upon
      cervical cytologic examination in Israeli Jewish women.
AB  - The adjusted incidence of cervical carcinoma among Israeli Jewish women is
      approximately 5 out of 100 000. This retrospective study sought to determine the
      clinical implications of finding atypical glandular cells of undetermined
      significance (AGUS) in cervical cytologic specimens in this population. Cervical
      cytologic examinations during January 2001-June 2003 diagnosed as AGUS were
      identified by a computerised database. Medical records were reviewed to determine
      the presence or absence of associated significant pathologic conditions of the
      cervix and identified 45 out of 11 800 patients (0.38%) with AGUS. AGUS was the
      only cytologic diagnosis in 14 patients, while 31 patients had both AGUS and an
      additional atypical squamous cell of undetermined significance (ASCUS). All
      subjects underwent colposcopy, endocervical curettage, and cervical biopsy. A
      clinically significant diagnosis (cervical intraepithelial neoplasia (CIN) II,
      CIN III, or carcinoma) was made in 24 patients (53.3%), including cancer in three
      (6.7%): one had microinvasive adenocarcinoma and two had microinvasive squamous
      cell carcinoma. Squamous carcinoma coexisting with a clinically significant
      lesion carried a risk of 61.3%, compared with a risk of 35.7% for AGUS alone
      (P=0.20). Detection of AGUS during cervical cytologic screening, especially with
      a coexisting ASCUS, indicates the existence of serious pathologic processes;
      management by cervical colposcopy, endocervical curettage, and cervical biopsy is
      recommended.

PMID- 15150574
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors.
AB  - Activation of the epidermal growth factor receptor (EGFR) has been linked to
      tumour proliferation, invasion, metastasis and angiogenesis in epithelial
      tumours. Inhibitors of the EGFR have emerged as promising anticancer agents and
      two main approaches have been developed, humanised monoclonal antibodies and
      tyrosine kinase inhibitors. This review discusses the current status of EGFR
      tyrosine kinase inhibitors (EGFR-TKIs) that have entered clinical development.
      EGFR-TKIs are generally well tolerated and can sometimes produce impressive
      tumour regression in patients with advanced non-small-cell lung cancer. However,
      highly predictive or surrogate markers of activity have not been identified and
      there remains a need for translational research in their future development.

PMID- 15150575
TI  - Fruit and vegetable consumption in relation to ovarian cancer incidence: the
      Swedish Mammography Cohort.
AB  - We prospectively examined the incidence of epithelial ovarian cancer and its
      subtypes in relation to baseline fruit and vegetable consumption in the Swedish
      Mammography Cohort, a population-based cohort study of 61 084 women aged 38-76
      years in 1987-1990. During an average follow-up of 13.5 years, 266 incident cases
      of invasive epithelial ovarian cancer were diagnosed. After adjustment for
      potential confounders, we observed a statistically significant inverse
      association between consumption of vegetables and ovarian cancer risk (P-value
      for trend=0.01); the multivariate rate ratio (RR) for the comparison of three or
      more servings of vegetables per day with one or fewer servings per day was 0.61
      (95% confidence interval (CI), 0.38-0.97). For fruit consumption a modest, not
      statistically significant, positive association was found (P-value for
      trend=0.07); the multivariate RR for the highest compared with the lowest
      category of consumption being 1.37 (95% CI, 0.90-2.06). The associations with
      fruit and vegetable consumption did not vary by subtype of ovarian cancer. These
      findings suggest that high consumption of vegetables, but not of fruits, may
      reduce the risk of ovarian cancer.

PMID- 15150576
TI  - Para-aortic irradiation for stage I testicular seminoma: results of a prospective
      study in 675 patients. A trial of the German testicular cancer study group
      (GTCSG).
AB  - A prospective nonrandomised trial was performed in order to evaluate tumour
      control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with
      treatment portals confined to the para-aortic lymph nodes. Between April 1991 and
      March 1994, 721 patients were enrolled for the trial by 48 centres in Germany.
      Patients with pure seminoma and no evidence of lymph node involvement or distant
      metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease
      free survival at 5 years was the primary end point. With a median follow-up of 61
      months, 675 patients with follow-up investigations were evaluable for this
      analysis. Kaplan-Meier estimates of disease-free and disease-specific survival
      were 95.8% (95% CI: 94.2-97.4) and 99.6% (95% CI: 99.2-100%) at 5 years and 94.9%
      (95% CI: 92.5-97.4%) and 99.6% (95% CI: 99.2-100%) at 8 years, respectively. A
      total of 26 patients relapsed. All except two were salvaged from relapse. In all,
      21 recurrences were located in infradiaphragmatic lymph nodes without any 'in
      field' relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the
      patients, respectively. Grade 3 late effects have not been observed so far. The
      results of our trial lend further support to the concept of limited para-aortic
      irradiation as the recently defined new standard of radiotherapy in stage I
      seminoma. There is no obvious compromise in disease-specific or disease-free
      survival compared to more extensive hockey-stick portals, which were used as
      standard portals at the time this study was initiated.

PMID- 15150577
TI  - Mitoxantrone resistance in a small cell lung cancer cell line is associated with
      ABCA2 upregulation.
AB  - The aim of this study was to find factors that could explain the accumulation
      difference of mitoxantrone in the BCRP1-negative GLC4-MITO cell line compared to
      GLC4. Comparative genomic hybridisation (CGH) was applied to determine
      chromosomal differences between GLC4 and GLC4-MITO. Comparative genomic
      hybridisation analysis revealed gain of 2q, 6p, 9q, 13q, 14q, 15q, 19q and Xp and
      loss of 1p, 2q, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p and Xq. In the over
      represented chromosomal areas, seven transporter genes were identified: ABCB6,
      ABCB2 (TAP1), ABCB3 (TAP2), ABCF1 (ABC50), ABCC10 (MRP7), ABCA2 (ABC2) and ABCC4
      (MRP4). No RNA or protein upregulation was observed for ABCB6, ABCF1, ABCC10,
      ABCC4, ABCB2 and ABCB3, but an increased expression was detected for ABCA2 mRNA
      in GLC4-MITO. ABCA2 is known to be involved in resistance to estramustine. In the
      MTT assay, GLC4-MITO was two-fold resistant to estramustine compared to GLC4.
      Coincubation with estramustine and mitoxantrone increased mitoxantrone
      accumulation in GLC4-MITO, while this was not affected in GLC4. This suggests
      that estramustine is able to block mitoxantrone efflux in GLC4-MITO cells. These
      data reveal that cellular reduction of mitoxantrone in a mitoxantrone-resistant
      cell line is associated with overexpression of ABCA2.

PMID- 15150578
TI  - In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour
      hypoxia with positron emission tomography.
AB  - Development of hypoxia-targeted therapies has stimulated the search for
      clinically applicable noninvasive markers of tumour hypoxia. Here, we describe
      the validation of [(18)F]fluoroetanidazole ([(18)F]FETA) as a tumour hypoxia
      marker by positron emission tomography (PET). Cellular transport and retention of
      [(18)F]FETA were determined in vitro under air vs nitrogen. Biodistribution and
      metabolism of the radiotracer were determined in mice bearing MCF-7, RIF-1, EMT6,
      HT1080/26.6, and HT1080/1-3C xenografts. Dynamic PET imaging was performed on a
      dedicated small animal scanner. [(18)F]FETA, with an octanol-water partition
      coefficient of 0.16+/-0.01, was selectively retained by RIF-1 cells under hypoxia
      compared to air (3.4- to 4.3-fold at 60-120 min). The radiotracer was stable in
      the plasma and distributed well to all the tissues studied. The 60-min
      tumour/muscle ratios positively correlated with the percentage of pO(2) values <5
      mmHg (r=0.805, P=0.027) and carbogen breathing decreased [(18)F]FETA-derived
      radioactivity levels (P=0.028). In contrast, nitroreductase activity did not
      influence accumulation. Tumours were sufficiently visualised by PET imaging
      within 30-60 min. Higher fractional retention of [(18)F]FETA in HT1080/1-3C vs
      HT1080/26.6 tumours determined by dynamic PET imaging (P=0.05) reflected higher
      percentage of pO(2) values <1 mmHg (P=0.023), lower vessel density (P=0.026), and
      higher radiobiological hypoxic fraction (P=0.008) of the HT1080/1-3C tumours. In
      conclusion, [(18)F]FETA shows hypoxia-dependent tumour retention and is, thus, a
      promising PET marker that warrants clinical evaluation.

PMID- 15150579
TI  - Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide
      administered intravenously every 3 weeks.
AB  - To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and
      pharmacokinetics of topotecan administered as a 30-min intravenous (i.v.)
      infusion over 5 days in combination with a 1-h i.v. infusion of ifosfamide (IF)
      for 3 consecutive days every 3 weeks. Patients with advanced malignancies
      refractory to standard therapy were entered into the study. The starting dose of
      topotecan was 0.4 mg x m(-2) day(-1) x 5 days. Ifosfamide was administered at a
      fixed dose of 1.2 g x m(-2) day(-1) x 3 days. In all, 36 patients received 144
      treatment courses. Owing to toxicities, the schedule of topotecan administration
      was reduced from 5 to 3 days. The MTD was reached at topotecan 1.2 mg x m(-2)
      day(-1) x 3 days with IF 1.2 g x m(-2) day(-1) x 3 days. Haematological
      toxicities were dose limiting. Neutropenia was the major toxicity.
      Thrombocytopenia and anaemia were rare. Nonhaematological toxicities were
      relatively mild. Partial responses were documented in three patients with ovarian
      cancer dosed below the MTD. Topotecan and IF did not appear to interact
      pharmacokinetically. The relationships between the exposure to topotecan lactone
      and total topotecan, and the decrease in absolute neutrophil count and the
      decrease in thrombocytes, were described with sigmoidal-E(max) models. The
      combination of 1.0 mg m(-2) day(-1) topotecan administered as a 30-min i.v.
      infusion daily times three with 1.2 g x m(-2) day(-1) IF administered as a 1-h
      i.v. infusion daily times three every 3 weeks was feasible. However, the
      combination schedule of topotecan and IF did result in considerable
      haematological toxicity and in conjunction with previously reported pronounced
      nonhaematological toxicities and treatment related deaths, it may be concluded
      that this is not a favourable combination.

PMID- 15150580
TI  - Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness.
AB  - The large numbers of papillary thyroid carcinomas that have occurred in those
      exposed to high levels of short-lived isotopes in fallout after Chernobyl provide
      a unique opportunity to correlate latency and tumour biology. We show that short
      latency is associated with tumours with a phenotype that is significantly less
      structurally differentiated, shows significantly less peritumour fibrosis, and
      significantly more invasive spread when compared to tumours with a longer latent
      period. In contrast, the type of differentiation (papillary or follicular
      architecture) is associated with age at exposure. These findings suggest that the
      initial mutation at the time of exposure played a major role in tumour latency
      and aggressiveness. We and others have shown that RET-PTC3 rearrangements are
      associated with the solid morphology seen in these short latency tumours, while
      classical papillary carcinomas more often show RET-PTC1 rearrangements. Studies
      in transgenic mice show similar findings, and in vitro studies show that RET-PTC3
      induces more rapid growth than RET-PTC1. We therefore suggest that the solid
      morphology, high frequency of RET-PTC3 rearrangements and aggressive behaviour
      noted in early investigations of post-Chernobyl tumours were characteristic of
      short latency rather than the nature of the mutagen, and that successive
      overlapping waves of papillary carcinoma with differing latency, differing
      patterns of mutations and differing clinical behaviour are occurring in those
      exposed to Chernobyl fallout.

PMID- 15150581
TI  - Prostate cancer and body size at different ages: an Italian multicentre case
      control study.
AB  - We investigated the influence of anthropometric measures at diagnosis and at
      different ages on prostate cancer risk using an Italian multicentre case-control
      study conducted between 1991 and 2002 of 1294 histologically confirmed cases and
      1451 controls admitted to the same network of hospitals for acute non-neoplastic
      conditions. Height, weight, body mass index (BMI), waist-to-hip ratio, lean body
      mass 1 year before diagnosis/interview were not significantly associated with
      risk. However, a positive association with high BMI at age 30 years was found
      (odds ratio=1.2 for BMI> or =24.7 vs <22.7) and: for less differentiated prostate
      cancer, with BMI 1 year before diagnosis/interview. This study supports possible
      relationships between high body mass in young adulthood, and a tendency to high
      weight throughout adult life, and the risk of prostate cancer.

PMID- 15150582
TI  - Risk of malignant lymphoma associated with human herpesvirus-8: a case-control
      study in Spain.
AB  - No overall increased risk of lymphoma associated with antibodies to human
      herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04,
      95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19
      lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade
      lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73).

PMID- 15150583
TI  - Diabetes mellitus and prostate cancer risk among older men: population-based case
      control study.
AB  - We investigate the relation between diabetes mellitus and risk of prostate cancer
      among older (age 65-79 years) men in a population-based case-control study of 407
      incident histologically confirmed cases registered in the South Carolina Central
      Cancer Registry between 1999 and 2001 (70.6% response rate); controls were 393
      men identified through the Health Care Financing Administration Medicare
      beneficiary file for South Carolina in 1999 (63.8% response rate). After
      adjusting for age, race, and prostate cancer screening in the past 5 years, a
      history of diabetes mellitus was associated with a reduced risk of prostate
      cancer (adjusted odds ratio (aOR)=0.64; 95% confidence interval (CI)=0.45, 0.91).
      The protective effect was stronger for those with complications associated with
      diabetes (aOR=0.61; 95% CI=0.42, 0.90) and for African-American men (aOR=0.36;
      95% CI=0.21, 0.62). Additional research is needed to understand the biologic
      mechanisms by which diabetes may influence prostate cancer risk; genetic factors
      may play an important role in understanding this association.

PMID- 15150584
TI  - Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound
      doxorubicin (SP1049C) in patients with advanced cancer.
AB  - SP1049C is a novel anticancer agent containing doxorubicin and two nonionic
      pluronic block copolymers. In preclinical studies, SP1049C demonstrated increased
      efficacy compared to doxorubicin. The objectives of this first phase I study were
      to determine the toxicity profile, dose-limiting toxicity, maximum tolerated dose
      and pharmacokinetic profile of SP1049C, and to document any antitumour activity.
      The starting dose was 5 mg m(-2) (doxorubicin content) as an intravenous infusion
      once every 3 weeks for up to six cycles. A total of 26 patients received 78
      courses at seven dose levels. The dose-limiting toxicity was myelosuppression and
      DLT was reached at 90 mg m(-2). The maximum tolerated dose was 70 mg m(-2) and is
      recommended for future trials. The pharmacokinetic profile of SP1049C showed a
      slower clearance than has been reported for conventional doxorubicin. Evidence of
      antitumour activity was seen in some patients with advanced resistant solid
      tumours. Phase II trials with this agent are now warranted to further define its
      antitumour activity and safety profile.

PMID- 15150585
TI  - Low value of detection of KRAS2 mutations in circulating DNA to differentiate
      chronic pancreatitis to pancreatic cancer.

PMID- 15150586
TI  - Breast cancer and induced abortions in China.

PMID- 15150587
TI  - Long-term results of a phase II study of synchronous chemoradiotherapy in
      advanced muscle invasive bladder cancer.
AB  - We conducted a phase I/II study investigating synchronous chemoradiotherapy with
      mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder
      cancer. Early dose escalation results were previously published. We report the
      long-term toxicity and efficacy results with the optimised regimen. Patients with
      muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1)
      were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg
      m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy
      of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68
      years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%)
      had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four
      patients experienced Grade III thrombocytopenia and three patients had Grade III
      neutropenia. There were no episodes of febrile neutropenia. Four patients
      experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients
      did not undergo cystoscopic evaluation due to early metastatic spread although
      there was no clinical suggestion of bladder failure. In all, out of 35 evaluable
      patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and
      biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with
      a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning
      bladder with no reported long-term treatment-related bladder or bowel toxicity.
      Five out of 41 patients have undergone salvage cystectomy: two for persistent
      CIS, two T1 and one muscle invasive recurrence. Four patients have received
      intravesical chemotherapy, of whom two remain alive with a functioning bladder.
      Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and
      distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m.
      Organ preservation using multimodality therapy is feasible and safe, even in
      patients with poor renal reserve, and does not compromise salvage therapies. A
      national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of
      synchronous chemoradiotherapy with this regimen is currently recruiting.

PMID- 15150588
TI  - Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features
      and patient survival in patients with prostate cancer.
AB  - Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) are important
      multifunctional cytokines involved in tumour growth and metastasis. In this
      study, we have measured serial levels of serum IL-6 and TNF-alpha in prostate
      cancer patients. A total of 80 patients with carcinoma of the prostate and 38
      controls were studied. Three patient groups, with small bulk localised, large
      volume localised and metastatic prostate cancer, were assessed. Serum IL-6 and
      TNF-alpha levels were measured and correlated with clinicopathological variables
      and patient survival. Serial changes in these cytokines were also assessed and
      related to disease progression in 40 patients with recurrent prostate cancer.
      Serum IL-6 levels in patients with metastatic disease (9.3+/-7.8 pg x ml(-1))
      were higher than those in patients with localised disease (1.3+/-0.8 pg x ml(-1),
      P<0.001). Significantly elevated levels of TNF-alpha were found in metastatic
      disease (6.3+/-3.6 pg x ml(-1)) compared with localised disease (1.1+/-0.5 pg x
      ml(-1), P<0.001). The levels of both cytokines were directly correlated with the
      extent of the disease. Serial analysis in 40 patients with recurrent tumours
      showed that both cytokines became elevated at the point of prostate-specific
      antigen progression. In conclusion, these results suggest that IL-6 and TNF-alpha
      correlate with the extent of disease in patients with prostate cancer and may be
      monitored in conjunction with other disease markers.

PMID- 15150589
TI  - Role of protein kinase C and NF-kappaB in proteolysis-inducing factor-induced
      proteasome expression in C(2)C(12) myotubes.
AB  - Proteolysis-inducing factor (PIF) is a sulphated glycoprotein produced by
      cachexia-inducing tumours, which initiates muscle protein degradation through an
      increased expression of the ubiquitin-proteasome proteolytic pathway. The role of
      kinase C (PKC) in PIF-induced proteasome expression has been studied in murine
      myotubes as a surrogate model of skeletal muscle. Proteasome expression induced
      by PIF was attenuated by 4alpha-phorbol 12-myristate 13-acetate (100 nM) and by
      the PKC inhibitors Ro31-8220 (10 microM), staurosporine (300 nM), calphostin C
      (300 nM) and Go 6976 (200 microM). Proteolysis-inducing factor-induced activation
      of PKC(alpha), with translocation from the cytosol to the membrane at the same
      concentration as that inducing proteasome expression, and this effect was
      attenuated by calphostin C. Myotubes transfected with a constitutively active
      PKC(alpha) (pCO(2)) showed increased expression of proteasome activity, and a
      longer time course, compared with their wild-type counterparts. In contrast,
      myotubes transfected with a dominant-negative PKC(alpha) (pKS1), which showed no
      activation of PKC(alpha) in response to PIF, exhibited no increase in proteasome
      activity at any time point. Proteolysis-inducing factor-induced proteasome
      expression has been suggested to involve the transcription factor nuclear factor
      kappaB (NF-kappaB), which may be activated through PKC. Proteolysis-inducing
      factor induced a decrease in cytosolic I-kappaBalpha and an increase in nuclear
      binding of NF-kappaB in pCO(2), but not in pKS1, and the effect in wild-type
      cells was attenuated by calphostin C, confirming that it was mediated through
      PKC. This suggests that PKC may be involved in the phosphorylation and
      degradation of I-kappaBalpha, induced by PIF, necessary for the release of NF
      kappaB from its inactive cytosolic complex.

PMID- 15150590
TI  - Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic
      potential of two murine cell lines.
AB  - In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of
      the microenvironmental characteristics of solid tumours. A number of studies have
      examined ways to increase tumour acidity in order to improve tumour-specific
      targeting of certain drugs and the effectiveness of hyperthermia. However,
      previous data have shown that exposure of murine tumour cells to acid conditions
      in culture can enhance their metastatic potential when injected subsequently into
      mice, raising the concern that deliberate tumour acidification might increase the
      probability of metastasis. In this study, we examined the effects of in vivo
      tumour acidification and hypoxia on the spontaneous metastatic potential of the
      murine KHT-C fibrosarcoma and B16F1 melanoma cell lines. A tumour-specific
      increase in extracellular acidity, demonstrated by measurements with pH
      electrodes, was achieved by daily intraperitoneal injections of meta-iodo
      benzylguanidine (MIBG) and/or glucose. This method of tumour acidification during
      tumour growth did not significantly enhance the spontaneous metastatic potential
      of the two murine cell lines.

PMID- 15150591
TI  - Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a
      meta-analysis.
AB  - While most cancers of the uterine cervix are squamous cell carcinomas, the
      relative and absolute incidence of adenocarcinoma of the uterine cervix has risen
      in recent years. It is not clear to what extent risk factors identified for
      squamous cell carcinoma of the cervix are shared by cervical adenocarcinomas. We
      used data from six case-control studies to compare directly risk factors for
      cervical adenocarcinoma (910 cases) and squamous cell carcinoma (5649 cases) in a
      published data meta-analysis. The summary odds ratios and tests for differences
      between these summaries for the two histological types were estimated using
      empirically weighted least squares. A higher lifetime number of sexual partners,
      earlier age at first intercourse, higher parity and long duration of oral
      contraceptive use were risk factors for both histological types. Current smoking
      was associated with a significantly increased risk of squamous cell carcinoma,
      with a summary odds ratio of 1.47 (95% confidence interval: 1.15-1.88), but not
      of adenocarcinoma (summary odds ratio=0.82 (0.60-1.11); test for heterogeneity
      between squamous cell and adenocarcinoma for current smoking: P=0.001). The
      results of this meta-analysis of published data suggest that squamous cell and
      adenocarcinomas of the uterine cervix, while sharing many risk factors, may
      differ in relation to smoking. Further evidence is needed to confirm this in view
      of the limited data available.

PMID- 15150592
TI  - Survival results of a multicentre phase II study to evaluate D2 gastrectomy for
      gastric cancer.
AB  - Curative resection is the treatment of choice for potentially curable gastric
      cancer. Two major Western studies in the 1990s failed to show a benefit from D2
      dissection. They showed extremely high postoperative mortality after D2
      dissection, and were criticised for the potential inadequacy of the pretrial
      training in the new technique of D2 dissection, prior to the phase III studies
      being initiated. The inclusion of pancreatectomy and splenectomy in D2 dissection
      was associated with increased morbidity and mortality. Following these results,
      we started a phase II trial to evaluate the safety and efficacy of pancreas
      preserving D2 dissection. The results of this trial regarding the safety of
      pancreas preserving D2 dissection were published in 1998. In this paper, we
      present the survival results of this phase II trial to confirm the rationale of
      carrying out a phase III study comparing D1 vs D2 dissection for curable gastric
      cancer. Italian patients with histologically proven gastric adenocarcinoma were
      registered in the Italian Gastric Cancer Study Group Multicenter trial. The study
      was carried out based on the General Rules of the Japanese Research Society for
      Gastric Cancer. A strict quality control system was achieved by a supervising
      surgeon of the reference centre who had stayed at the National Cancer Center
      Hospital, Tokyo, to learn the standard D2 gastrectomy and the postoperative
      management. The standard procedure entailed removal of the first and second tier
      lymph nodes. During total gastrectomy, the pancreas was preserved according to
      the Maruyama technique. Complete follow-up was available to death or 5 years in
      100% of patients and the median follow-up time was 4.38 years. Out of 297
      consecutive patients registered, 191 patients were enrolled in the study between
      May 1994 and December 1996. The overall morbidity rate was 20.9%. The
      postoperative in-hospital mortality was 3.1%. The overall 5-year survival rate
      among all eligible patients was 55%. Survival was strictly related to stage,
      depth of wall invasion, lymph node involvement and type of gastrectomy (distal vs
      total). Our results suggest a survival benefit for pancreas-preserving D2
      dissection in Italian patients with gastric cancer if performed in experienced
      centres. A phase III trial among exclusively experienced centres is urgently
      needed.

PMID- 15150593
TI  - Differentiation-dependent photodynamic therapy regulated by porphobilinogen
      deaminase in B16 melanoma.
AB  - Protoporphyrin IX (PpIX) synthesis by malignant cells is clinically exploited for
      photodiagnosis and photodynamic therapy following administration of 5
      aminolevulinic acid (ALA). The expression and activity of the housekeeping
      porphobilinogen deaminase (PBGD) was correlated to PpIX synthesis in
      differentiating B16 melanoma cells. Differentiation was stimulated by two
      inducers, butyrate and hexamethylene bisacetamide (HMBA), both of which promote
      the formation of typical melanosomes and melanin, as well as morphological
      changeover. A marked decrease in total PBGD activity and PpIX synthesis was
      observed following stimulation by butyrate, while HMBA induced an opposite
      effect. In contrast, ferrochelatase levels remained unchanged. Photodynamic
      inactivation of the cells undergoing differentiation was largely dependent on the
      PpIX accumulation, which was modulated by the two inducers butyrate and HMBA.
      Fluorescence immunostaining with anti-PBGD antibodies revealed a major PBGD
      fraction in the nucleus and a minor fraction in the cytosol. This nuclear
      localisation pattern was confirmed by expression of PBGD fused to green
      fluorescence protein. We suggest that efficient photodynamic therapy of cancer
      facilitated by ALA administration can be enhanced using combined therapeutic
      modalities.

PMID- 15150594
TI  - Impact of antibody framework residue VH-71 on the stability of a humanised anti
      MUC1 scFv and derived immunoenzyme.
AB  - Anti-MUC1 single-chain Fv (scFv) fragments generated from the humanised antibody
      huHMFG1 had adequate antigen-binding properties but very poor stability
      irrespective of the applied linker or domain orientation. Mutagenesis of heavy
      chain framework residue V(H)-71, previously described as a key residue for
      maintaining the CDR-H2 main-chain conformation and thus important for antigen
      binding, markedly stabilised the scFv while having only a minor effect on the
      binding affinity of the molecule. Because of its improved stability, the
      engineered fragment exhibited immunoreactivity with tumour cells even after 7
      days of incubation in human serum at 37 degrees C. It also showed, in contrast to
      the wild-type scFv, a concentration-dependent binding to the target antigen when
      displayed on phage. When fusing the scFv to the recombinant ribonuclease rapLRI,
      only the fusion protein generated with the stable mutant scFv was able to kill
      MUC1(+) tumour cells with an IC(50) of 80 nM. We expect this novel immunoenzyme
      to become a promising tool for the treatment of MUC1(+) malignancies.

PMID- 15150595
TI  - Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64
      cases.
AB  - Small-cell carcinoma (SmCC) of the gastrointestinal tract is a very rare and
      aggressive malignancy. To better define its clinicopathological features, the
      records of all patients with this disease seen at Memorial Sloan Kettering Cancer
      Center between 1980 and 2002 (n=64) were reviewed. The most common primary tumour
      locations were in the large bowel and oesophagus. Predisposing medical conditions
      for non-small-cell cancers, positive family cancer history, and metachronous
      tumours were common. In all, 37% had mixed tumour histology and 48% presented
      with extensive disease, according to the Veterans' Administration Lung Study
      group (VALSG) staging system used for small-cell lung cancer. Treatment outcome
      in limited disease (LD) suggested a role for surgery and chemotherapy. Platinum
      based regimens resulted in a 50% response rate. The 2-year survival was 23% and
      two prognostic factors were identified, the extent of disease according to the
      VALSG system (P<0.01) and TNM stage (P=0.03). Anatomic location had no clinical
      impact. In conclusion, SmCC from various gastrointestinal sites can be viewed as
      one clinical entity. Mixed tumour histology is common and may affect therapy.
      Surgery, combined with chemotherapy, should be considered for LD. The value of
      the VALSG system was implied and possible differences from small-cell lung cancer
      were noted.

PMID- 15150596
TI  - Evaluation of a cumulative prognostic score based on the systemic inflammatory
      response in patients undergoing potentially curative surgery for colorectal
      cancer.
AB  - The value of combining Dukes' stage and C-reactive protein to form a cumulative
      prognostic score was assessed in 147 patients undergoing potentially curative
      resection for colorectal cancer. The cancer-specific survival rates at 3 years
      for patients with a cumulative prognostic score of 0, 1 and 2 were 100, 77 and
      40%, respectively (HR 4.76, 2.78-8.15, P<0.001).

PMID- 15150597
TI  - Lower protection of cytological screening for adenocarcinomas and shorter
      protection for younger women: the results of a case-control study in Florence.
AB  - The efficacy of cytological screening in preventing adenocarcinoma of cervix
      uteri as compared to squamous cell cancer has been evaluated by means of a case
      control study in the province of Florence. The odds ratios of women who had a Pap
      test within the 3 years before the index date was 0.65 (95% confidence interval
      (CI) 0.26-1.64) and 0.15 (95% CI 0.07-0.31), for adenocarcinoma and squamous
      cancer, respectively. The duration of the protective effect was shorter in women
      below the age of 40 years than in older women.

PMID- 15150598
TI  - Total body irradiation and pneumonitis risk: a review of outcomes.
AB  - A review was undertaken of all patients treated at Royal Adelaide Hospital, South
      Australia with total body irradiation (TBI) for the purpose of assessing the
      incidence of interstitial pneumonitis (IP) and possible prognostic factors for
      its development. The aim was also to assess the impact of IP and other prognostic
      factors on long-term survival outcome following bone marrow transplantation. A
      total of 84 patients received TBI, with 12 Gy in six fractions delivered using
      two different instantaneous dose rates of 7.5 and 15 cGy min(-1). This series
      included 26 cases of acute lymphoblastic leukaemia, 26 of multiple myeloma and 15
      of acute myelogenous leukaemia. On multivariate analysis, a higher dose rate was
      independently significant for an increased risk of IP.

PMID- 15150599
TI  - The increase of MICA gene A9 allele associated with gastric cancer and less
      schirrous change.
AB  - Since surgical resection is the principal treatment of gastric cancer, early
      detection is the only effective strategy against this disease at present.
      Recently, a new polymorphic gene family, the major histocompatibility complex
      class I chain-related (MIC) genes located about 40 kb centromeric to HLA-B gene
      has been proposed. This family consists of five genes (A, B, C, D and E). Among
      them, MICA has five various alleles (A4, A5, A5.1, A6 and A9), which can be used
      as a polymorphic marker for genetic mapping and for disease susceptibility. The
      MICA polymorphism was studied in our gastric cancer patients to see if there is
      any possible correlation with genetic predisposition and clinicopathological
      factors. Genomic DNA was extracted from fresh or frozen peripheral blood
      leukocytes in 107 patients with gastric adenocarcinoma who underwent gastrectomy
      in our hospital and 351 noncancer controls. MICA polymorphism was analysed by
      using PCR-based technique. The results showed both phenotypic and allele
      frequencies of allele A9 in patients with gastric cancer were significantly
      higher than controls (33 vs 17.6%, P=0.005; 17 vs 9.9%, P=0.02). Gastric
      adenocarcinoma with allele A9 was associated with less schirrous change than
      those without (P=0.014). MICA gene A9 allele might confer the risk of gastric
      cancer and associate with less schirrous change. The mechanisms among them
      deserve further investigation.

PMID- 15150601
TI  - Breast cancer mortality trends in two areas of the province of Florence, Italy,
      where screening programmes started in the 1970s and 1990s.
AB  - We compared breast cancer mortality rates in the period 1985-2000 in two areas of
      the province of Florence, Italy, where breast cancer screening programmes started
      in the 1970s (early screening (ES) area) and in 1990s (late screening (LS) area).
      The overall age-standardised mortality decreased in the whole period by 40.9% in
      the ES area (P<0.001), and by 11.3% in the LS area (P=0.030). Significant
      decreases in the ES area were detected in groups aged 45-54 years (61.1%; P=
      0.018) and 65-74 years (44.7%; P= 0.049), whereas in the LS area no significant
      decrease was detected in any age group. The relatively low compliance in the
      first years of the programme in both areas, and the long enrollment period in the
      LS area could have reduced the effect on mortality. Our findings suggest that the
      drop in mortality in the ES area (41%) could be explained by both service
      screening and better care. The slight decrease in mortality in the LS area (11%)
      could be mainly due to better care. A reduction of about 30% is attributable to
      screening in the ES area over the period 1985-2000.

PMID- 15150600
TI  - Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma
      with poor prognosis.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant human tumours because
      of its high incidence of metastasis. The mechanisms underlying the metastasis of
      HCC, however, remain poorly understood. In this study, we performed cDNA
      microarray analysis to profile gene expression patterns in two subtypes of HCC,
      solitary large HCC (SLHCC) and nodular HCC (NHCC), which differ significantly in
      the incidence of metastasis. Among 668 genes that were differentially expressed,
      we focused on RhoC, whose expression was significantly decreased in SLHCC
      compared to NHCC. The expression of RhoC in HCC and pericarcinomatous liver
      tissues (PCLT) was analysed at both the mRNA and protein levels by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting. In
      addition, immunohistochemistry was also performed on 94 cases of HCC with follow
      up information. Collectively, our data indicate that the expression of RhoC
      significantly increased in HCC compared to PCLT; extrahepatic metastatic lesions
      expressed significantly higher levels of RhoC than the corresponding intrahepatic
      HCC tissues. There is a highly significant correlation of the RhoC expression
      levels with tumour vein invasion, number of tumour nodes and the status of
      differentiation. Significantly, the HCC patients with RhoC-positive expression
      had shorter survival than those with RhoC-negative expression. Together, our
      findings suggest a strong correlation between the expression of RhoC and HCC
      metastasis, implicating RhoC as a potential prognosis marker and therapeutic
      target for HCC.

PMID- 15150602
TI  - Epidermodysplasia verruciformis human papillomavirus types and carcinoma of the
      conjunctiva: a pilot study.
AB  - A total of 21 squamous-cell carcinoma of the conjunctiva (SCC) and 22 control
      subjects had conjunctival samples tested for human papillomavirus (HPV) types
      using PCR-based assays. Epidermodysplasia verruciformis HPV types were found in
      86% of SCC cases and 36% of control subjects (Odds ratio=12.0), suggesting a role
      of HPVs in the aetiology of SCC.

PMID- 15150603
TI  - Childhood leukaemia incidence and the population mixing hypothesis in US SEER
      data.
AB  - We evaluated the infectious aetiology hypothesis of childhood leukaemia that
      rapid population influx into rural areas is associated with increased risk. Using
      data from the US SEER program, we found that in changes in rural county
      population sizes from 1980 to 1989 were associated with incidence rates for
      childhood acute lymphocytic leukaemia (ALL). The observed associations were
      strongest among children 0-4 years of age, born in the same state as diagnosis,
      in extremely rural counties, and when counties adjacent to nonrural counties were
      excluded. Similar analyses for brain and central nervous system (CNS) cancer in
      children, a disease less linked to this infectious hypothesis, provide evidence
      against methodologic bias. Similar evaluations for other decades were not
      meaningful due to limited sample sizes and, perhaps, increased population
      mobility.

PMID- 15150604
TI  - Aromatase inhibition in the treatment of advanced breast cancer: is there a
      relationship between potency and clinical efficacy?
AB  - Two-thirds of breast tumours are oestrogen-receptor positive and 60-70% of these
      tumours respond to interventions that reduce the effects of oestrogen. Until
      recently, tamoxifen was the drug of choice for the treatment of hormone
      responsive early and advanced breast cancer. However, tamoxifen is associated
      with increased incidences of endometrial cancer and thromboembolic disease, and
      many tumours eventually become resistant to treatment with tamoxifen. Thus, there
      is a need for alternative therapies with different mechanisms of action. In
      postmenopausal women, aromatase inhibitors (AIs) suppress oestrogen levels by
      inhibiting oestrogen synthesis via the aromatase enzyme pathway. The third
      generation AIs (anastrozole, letrozole and exemestane) are more potent than the
      earlier AIs (aminoglutethimide, formestane and fadrozole) with respect to both
      aromatase inhibition and oestrogen suppression. While the earlier AIs were unable
      to show any benefit over megestrol acetate or tamoxifen as second- and first-line
      therapy, respectively, in postmenopausal women with advanced breast cancer, third
      generation AIs have shown significant benefits in both settings. Comparison of
      aromatase inhibition and oestrogen suppression between the third-generation AIs
      anastrozole and letrozole showed a small but significantly greater difference in
      the degree of suppression of oestrone and oestrone sulphate (but not oestradiol),
      with letrozole. In an open-label trial, there were no significant differences
      between letrozole and anastrozole for the clinical end points of time to
      progression (primary end point), time to treatment failure, overall survival,
      clinical benefit, duration of clinical benefit, time to response, duration of
      response or objective response rate in patients with confirmed hormone receptor
      positive tumours. Together these data suggest that once a certain threshold of
      aromatase inhibition is reached, small differences in oestrogen suppression
      between the third-generation AIs do not lead to clinically significant
      differences in overall efficacy.

PMID- 15150605
TI  - Negative human papillomavirus testing in normal smears selects a population at
      low risk for developing high-grade cervical lesions.
AB  - High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical
      carcinomas and there is an increasing interest in using HR-HPV DNA detection in
      adjunction to cytological examination for primary cervical screening. To
      determine whether women with a normal smear negative for HR-HPV DNA detection
      with the Hybrid Capture II assay might represent a low-risk population for
      developing a high-grade squamous intraepithelial lesion (HSIL), 4401 women have
      been followed in a period of 12-72 months (median=34 months). During this follow
      up, four HSIL and one microinvasive carcinoma have been detected in this cohort
      (three in the cohort of 3526 women >29 years). The global negative predictive
      value (NPV) of double-negative tests is thus of 99.9% (ninety-five percent
      confidence interval (95% CI): 99.8-100%), whereas cytology alone gives an NPV of
      99.2% (95% CI: 98.9-99.5%). If we obtain a second negative HR-HPV test 1-2 years
      after the initial test, the NPV is 100%. The NPV is also of 100% in the cohort of
      women >49 years. We conclude that all these women could be safely screened at
      longer intervals between 3 and 5 years. This policy will offset the increased
      costs induced by an additional HR-HPV testing in primary screening.

PMID- 15150606
TI  - Osteopontin expression correlates with adhesive and metastatic potential in
      metastasis-inducing DNA-transfected rat mammary cell lines.
AB  - A metastatic phenotype can be induced in benign rat mammary cells (Rama 37 cells)
      by transfecting them with metastasis-inducing DNAs (Met-DNAs). Stable
      transfection of Met-DNAs increases the level of the metastasis-associated
      protein, osteopontin. Randomly picked clonal cell lines have been established
      from the pool of Rama 37 cells transfected with one metastasis-inducing DNA, C9
      Met-DNA. In these cell lines, moderate correlation is observed between the copy
      number of C9-Met-DNA and their metastatic potential (linear regression
      coefficient, R(2)=0.48). A very close correlation is observed between the cell
      lines' metastatic potential in vivo and the osteopontin mRNA levels in vitro
      (R(2)=0.74), but not with another metastasis-associated protein in this system,
      S100A4 (R(2)=0.21). A close correlation is also observed between osteopontin mRNA
      levels and the adhesive potential (R(2)=0.91) of the cells, but not with their
      growth rate in vitro (R(2)=0.03). These observations support the previous
      suggestion that osteopontin is the direct effector of C9-Met-DNA and that the
      presence of C9-Met-DNA is necessary, if not sufficient, for the induction of
      metastasis in vivo in this system. Additionally, these results suggest that Rama
      37 cells with increased osteopontin mRNA levels become metastatic not through an
      increased growth rate, but through an increase in cellular adhesiveness.

PMID- 15150607
TI  - Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and
      induction of apoptosis in H 209 small cell lung cancer cells.
AB  - Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor
      kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC
      growth is also driven by insulin-like growth factor-1 receptor (IGF-1R)
      signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-1R and c-kit
      activity, respectively) were used to co-target these receptors in H 209 SCLC
      cells. Combination treatment caused synergy in proliferation inhibition and in
      apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2,
      suggesting that co-targeting IGF-1R and c-kit in SCLC may be more effective than
      single-agent therapies.

PMID- 15150609
TI  - Estimation and projection of the national profile of cancer mortality in China:
      1991-2005.
AB  - There are no national-level data on cancer mortality in China since two surveys
      in 1973-1975 and 1990-1992 (a 10% sample), but ongoing surveillance systems,
      based on nonrandom selected populations, give an indication as to the trends for
      major cancers. Based on a log-linear regression model with Poisson errors, the
      annual rates of change for 10 cancers and all other cancers combined, by age, sex
      and urban/rural residence were estimated from the data of the surveillance system
      of the Center for Health Information and Statistics, covering about 10% of the
      national population. These rates of change were applied to the survey data of
      1990-1992 to estimate national mortality in the year 2000, and to make
      projections for 2005. Mortality rates for all cancers combined, adjusted for age,
      are predicted to change little between 1991 and 2005 (-0.8% in men and +2.5% in
      women), but population growth and ageing will result in an increasing number of
      deaths, from 1.2 to 1.8 million. The largest predicted increases are for the
      numbers of female breast (+155.4%) and lung cancers (+112.1% in men, +153.5% in
      women). For these two sites, mortality rates will almost double. Cancer will make
      an increasing contribution to the burden of diseases in China in the 21st
      century. The marked increases in risk of cancers of the lung, female breast and
      large bowel indicate priorities for prevention and control. The increasing trends
      in young age groups for cancers of the cervix, lung and female breast suggest
      that their predicted increases may be underestimated, and that more attention
      should be paid to strategies for their prevention and control.

PMID- 15150608
TI  - Neuropsychological dysfunction associated with cancer and cancer therapies: a
      conceptual review of an emerging target.
AB  - Neuropsychological dysfunction associated with cancer and cancer treatment is a
      growing concern. Methodological limitations permeate the corpus of research in
      this area and have limited our understanding of the multifactorial nature of this
      process. The following review provides a summary of the current state of
      knowledge and highlights future directions.

PMID- 15150610
TI  - Geographical variation in breast cancer survival rates for women diagnosed in
      England between 1992 and 1994.
AB  - The 5-year relative survival rates of women diagnosed with breast cancer between
      1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of
      England. Substantial variation, with evidence of geographical clustering was
      observed. Part of this variation was explained by differences in deprivation
      between Health Authorities, in particular by the percentage of class IV and V
      households. British Journal of Cancer (2004) 90, 2153-2156.
      doi:10.1038/sj.bjc.6601812 www.bjcancer.com Published online 27 April 2004

PMID- 15150611
TI  - A phase I study with MAG-camptothecin intravenously administered weekly for 3
      weeks in a 4-week cycle in adult patients with solid tumours.
AB  - In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked
      to a water-soluble polymer. Preclinical experiments showed enhanced antitumour
      efficacy and limited toxicity compared to camptothecin alone. Prior phase I
      trials guided the regimen used in this study. The objectives were to determine
      the maximum tolerated dose, dose-limiting toxicities, safety profile, and
      pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT
      intravenously administered weekly for 3 weeks in 4-week cycles. At the starting
      dose level (80 mg x m(-2) week(-1)), no dose-limiting toxicities occurred during
      the first cycle (n=3). Subsequently, three patients were enrolled at the second
      dose level (120 mg x m(-2) week(-1)). Two of three patients at the 80 mg x m(-2)
      week(-1) cohort developed haemorrhagic cystitis (grade 1/3 dysuria and grade 2/3
      haematuria) during the second and third cycles. Next, the 80 mg x m(-2) week(-1)
      cohort was enlarged to a total of six patients. One other patient at this dose
      level experienced grade 1 haematuria. At 120 mg x m(-2) week(-1), grade 1 bladder
      toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg
      x m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg
      x m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin
      excretion, associated with bladder toxicity. Due to cumulative bladder toxicity,
      weekly MAG-CPT is not a suitable regimen for treatment of patients with solid
      tumours.

PMID- 15150612
TI  - Loss of NOS1 expression in high-grade renal cell carcinoma associated with a
      shift of NO signalling.
AB  - In normal human kidney, NOS1 and soluble guanylate cyclase (sGC) are expressed in
      tubular epithelial cells, suggesting a physiological autocrine NO signalling
      pathway. Therefore, we investigated both NOS1 and sGC expressions in benign and
      malignant renal tumours. In addition, we examined the pattern of protein tyrosine
      nitration in normal and tumour tissue. NOS1 expression and activity were found to
      be downregulated, correlating with the tumour grade, as shown by
      immunohistochemistry, quantitative RT-PCR analysis, and histochemical detection
      of the NADPH-diaphorase activity of nitric oxide synthases (NOS). These results
      show that the autocrine NO signalling pathway is maintained in benign tumours and
      lost in malignant tumours. In contrast, sGC expression was maintained in renal
      tumours whatever the tumour type, a finding showing that tumour cells remain
      sensitive to the bioregulatory role of exogeneous NO(*). Finally, the staining
      pattern of protein tyrosine nitration, assessed by immunohistochemistry,
      parallelled that of NOS1 expression in normal renal parenchyma and benign
      tumours, supporting the concept that protein nitration was accounted for by NOS1
      activity. In contrast, in malignant tumours, protein tyrosine nitration was
      accounted for by the production of reactive nitrogen oxide species by the
      inflammatory infiltrate. Altogether, these findings argue for a pattern of NO
      signalling similar in normal kidney and benign renal tumours, whereas it is
      completely different in malignant renal tumours.

PMID- 15150616
TI  - Confounding effect of socioeconomic position in the study of height in relation
      to prostate cancer risk.

PMID- 15150613
TI  - Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma.
AB  - Recent studies indicated nm23-H1 played a role in cancer progression. Therefore,
      we investigated clinical significance of nm23-H1 expression in oral squamous cell
      carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained
      with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23
      H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and
      clinicopathologic variables were evaluated by chi(2) analysis. As increased size
      of primary tumour could escalate metastatic potential and the data of patients at
      the late T stage might confound statistical analyses, we thus paid special
      attention to 54 patients at the early T stage of OSCC. Statistical difference of
      survival was compared by a log-rank test. Immunohistochemically, nm23-H1
      expression was detected in 48.8% (42 out of 86) of tumorous specimens. It
      positively correlated with larger primary tumour size (P=0.03) and inversely with
      cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased
      nm23 expression was associated with increased incidence of lymph node metastasis
      (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a
      prognostic factor for predicting better survival in OSCC patients at the early T
      stage, which may reflect antimetastatic potential of nm23. Therefore, modulation
      of nm23-H1 expression in cancer cells can provide a novel possibility of
      improving therapeutic strategy at this stage. In addition, our results further
      indicated cigarette smoking could aggravate the extent of nm23-H1 expression and
      possibly disease progression of OSCC patients.

PMID- 15150617
TI  - Screening for colorectal cancer with immunological FOBT.

PMID- 15150618
TI  - Interaction between cyclooxygenase-2 gene polymorphism and dietary n-6
      polyunsaturated fatty acids on colon cancer risk: the Singapore Chinese Health
      Study.
AB  - This case-control study of 310 colorectal cancer cases and 1177 controls in a
      nested prospective, population-based cohort of Singapore Chinese subjects found a
      statistically significant association between the cyclooxygenase (COX)-2 -765G>C
      gene polymorphism and colon cancer risk among high consumers of dietary n-6
      polyunsaturated fatty acids (odds ratio=2.38, 95% confidence interval=1.23-4.59).

PMID- 15150619
TI  - Weekly gemcitabine plus 24-h infusion of high-dose 5-fluorouracil/leucovorin for
      locally advanced or metastatic carcinoma of the biliary tract.
AB  - Both gemcitabine and weekly 24-h infusion of high-dose 5-fluorouracil/leucovorin
      (HDFL) have shown promising antitumour activity for patients with locally
      advanced or metastatic carcinoma of the biliary tract (CBT). From April 1999
      through December 2002, 30 patients with inoperable CBT were treated with
      gemcitabine 800 mg m(-2), intravenous infusion for 30 min, followed by 5-FU, 2000
      mg m(-2) and leucovorin, 300 mg m(-2), intravenous infusion for 24 h, on day 1, 8
      and 15, every 4 weeks. A total of 166 cycles were given (median of four cycles
      per patient, range 1-24 cycles). Response was evaluable in 28 patients and
      toxicity in 29 patients. Partial response was obtained in six patients, stable
      disease in 13, while progressive disease occurred in nine. The objective response
      rate was 21.4% (95% CI: 5.2-37.6%). The most common grade 3 or 4 toxicity was
      infection (nine patients). Other types of grade 3 or 4 toxicity included
      leucopenia (four patients), thrombocytopenia (three patients), anaemia (three
      patients), nausea/vomiting (two patients) and elevation of liver transaminases
      (three patients). As of 30 September 2003, the median progression-free survival
      was 3.7 months (95% CI: 2.8-4.6 months) and the median overall survival was 4.7
      months (95% CI: 0.8-8.6 months). Our data suggest that weekly gemcitabine plus
      HDFL is modestly active with acceptable treatment-related toxicity for patients
      with advanced CBT.

PMID- 15150620
TI  - In utero alcohol exposure increases mammary tumorigenesis in rats.
AB  - Findings in humans and animal models suggest that in utero hormonal and dietary
      exposures increase later breast cancer risk. Since alcohol intake by adult women
      consistently increases their breast cancer risk, we wondered whether maternal
      alcohol consumption during pregnancy increases female offspring's mammary
      tumorigenesis. In our study, pregnant female rats were pair-fed isocaloric diets
      containing either 0 (control), 16 or 25 g alcohol kg(-1) feed between days 7 and
      19 of gestation. These alcohol exposures generate blood alcohol levels that
      correspond to low and moderate alcohol consumption and are lower than those that
      induce foetal alcohol syndrome. Serum oestradiol levels were elevated in pregnant
      rats exposed to alcohol (P<0.003). When adult, female offspring of alcohol
      exposed dams developed significantly more 7,12-dimethylbenz[a]anthracene -induced
      mammary tumours, compared to the controls (tumour multiplicity; mean+/-s.e.m.,
      controls: 2.0+/-0.3, 16 g alcohol: 2.7+/-0.4 and 25 g alcohol: 3.7+/-0.4;
      P<0.006). In addition, the mammary epithelial tree of the alcohol-exposed
      offspring was denser (P<0.004) and contained more structures that are susceptible
      for the initiation of breast cancer (P<0.001). Immunohistochemical assessment
      indicated that the mammary glands of 22-week-old in utero alcohol-exposed rats
      contained elevated levels of oestrogen receptor-alpha (P<0.04) that is consistent
      with the changes in mammary gland morphology. In summary, maternal alcohol intake
      during pregnancy increases female offspring's mammary tumorigenesis, perhaps by
      programming the foetal mammary gland to exhibit persistent alterations in
      morphology and gene expression. It remains to be determined whether an increase
      in pregnancy oestradiol levels mediated alcohol's effects on offspring's mammary
      tumorigenesis.

PMID- 15150621
TI  - Cancer genetics services: a systematic review of the economic evidence and
      issues.
AB  - This paper systematically reviews the published economic research upon cancer
      genetics services for families at risk of having familial breast, ovarian or
      colorectal cancer. A structured search was made of 15 electronic databases. The
      search identified 1030 papers, of which 31 fulfilled the inclusion criteria, two
      were cost-benefit studies, five were cost consequences, four were cost
      effectiveness studies, one was a cost analysis, two were cost-minimisation
      studies, one was a cost-utility study, 10 modelled life years and six were
      reviews. Modelling studies indicate that surveillance, prophylactic and
      chemoprevention techniques extend survival for carriers of identified mutations.
      Genetic testing has been estimated to cost 70-2400 USD [48-1591 UK pounds] and
      genetic counselling 129-800 USD [89-551 UK pounds]. The technology of genetic
      testing has been found to be cost effective. Cost effectiveness was particularly
      influenced by targeting genetic services for patients with a strong family
      history of cancer rather than screening the entire population. Future economic
      evaluation must go beyond merely assessing health outcomes and mutation
      identification, and account for the impact of genetic services upon the
      individual, the family and society, establish the value of services to these
      groups and determine the most effective ways of delivering genetic services.

PMID- 15150622
TI  - Comparison of an inflammation-based prognostic score (GPS) with performance
      status (ECOG) in patients receiving platinum-based chemotherapy for inoperable
      non-small-cell lung cancer.
AB  - The value of an inflammation-based prognostic score (GPS) was compared with
      performance status (ECOG) in patients (n=109) receiving platinum-based
      chemotherapy for inoperable non-small-cell lung cancer. On multivariate analysis
      with ECOG, white cell count and the GPS entered as covariates, only the GPS was a
      significant independent predictor of survival (HR 1.88, 95% CI 1.25-2.84,
      P=0.002).

PMID- 15150624
TI  - Phase II study of capecitabine in combination with paclitaxel in patients with
      anthracycline-pretreated advanced/metastatic breast cancer.
AB  - The addition of oral capecitabine to docetaxel improves response rate, time to
      progression (TTP) and overall survival in anthracycline-pretreated metastatic
      breast cancer (MBC). This phase II study evaluates the efficacy and safety of a
      21-day cycle of oral capecitabine (1000 mg m(-2) twice daily, days 1-14) plus
      i.v. paclitaxel (175 mg m(-2), day 1) in anthracycline-pretreated advanced/MBC.
      In all, 73 patients were enrolled at 13 Swedish and Spanish centres. The
      objective response rate was 52% (95% confidence interval (CI): 40-63%) in the
      intent-to-treat population, including complete responses in 11%. Disease was
      stabilised in a further 29%. The median time to disease progression (TTP) was 8.1
      months and the median overall survival was 16.5 months. The combination was
      generally well tolerated with a predictable safety profile. The most common
      treatment-related nonhaematological adverse events were hand-foot syndrome (42%),
      alopecia (30%) and diarrhoea (26%). The only treatment-related Grade 3/4 adverse
      events occurring in >5% of patients were alopecia (22%) and hand-foot syndrome
      (11%). Grade 3/4 neutropenia and lymphocytopenia were reported in 12 and 14% of
      patients, respectively. Capecitabine plus paclitaxel is highly active with a
      favourable safety profile in anthracycline-pretreated MBC.

PMID- 15150623
TI  - Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin
      plus paclitaxel in patients with advanced ovarian cancer in early progression
      after platinum-based chemotherapy: an Italian Collaborative Study from the Mario
      Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R.
      (Istituto Oncologico Romagnolo) group.
AB  - The aim of the study was to evaluate the role of epidoxorubicin plus paclitaxel
      combination (ET) vs single agent paclitaxel (T), as second-line chemotherapy
      treatment in advanced ovarian cancer patients in early progression within 12
      months after platinum-based chemotherapy. From October 1994 up to June 1999, 234
      patients from 34 Italian hospitals were randomised to receive: (A) epidoxorubicin
      (E) 80 mg m(-2) + paclitaxel (T) 175 mg m(-2) (3 h infusion), every 21 days for 4
      6 cycles. (B) Paclitaxel 175 mg m(-2) (3 h infusion) every 21 days for 4-6
      cycles. Evaluable for survival analysis were 106 and 106 patients in ET and T
      arm, respectively. Platinum-based monochemotherapy was the first-line treatment
      in 43% patients, while polichemotherapy containing anthracyclines was the
      preferred first-line therapy in 22% patients. The median time from the end of
      first-line therapy to randomisation was 3 months. Treatment was completed in 87
      and 85% of T and ET arm, respectively. Haematological toxicity was significantly
      more common in ET group (ECOG grade 3-4 neutropenia: 37.4% in ET vs 18.2% in T
      arm). Neuropathies were similar in both arms (sensory: ECOG grade 2-3: 12.1% in
      ET vs 14.7% in T arm, motor: 6.1% in ET vs 5.3% in T arm). Objective response was
      achieved in 37.4% of patients in ET group and in 46.9% of patients in T arm. At a
      median follow-up of time of 48 months, a total of 180 patients progressed and 163
      patients died. Survival analysis showed no difference between ET and T (median
      time to progression: 6 months for both regimens, median survival: 12 and 14
      months for ET and T, respectively; hazard ratio for mortality of ET vs T: 1.17
      (95% CI 0.86-1.59; P=0.33). The ET regimen does not seem to be more effective
      than T in refractory advanced ovarian cancer patients in early progression after
      platinum-based chemotherapy. Despite an acceptable response rate, the control of
      disease progression remains poor.

PMID- 15150625
TI  - A novel biweekly multidrug regimen of gemcitabine, oxaliplatin, 5-fluorouracil (5
      FU), and folinic acid (FA) in pretreated patients with advanced colorectal
      carcinoma.
AB  - Previous results suggest that GEM affects 5-fluorouracil (5-FU) metabolism and
      pharmacokinetics in cancer patients, while combined with oxaliplatin, levo
      folinic acid, and 5-FU (GOLF regimen), at doses achievable in cancer patients,
      determines high cytotoxic and proapoptotic antitumour activity in colon cancer
      cells in vitro. On these bases we designed a phase I-II clinical trial testing
      the GOLF regimen in patients with metastatic colorectal carcinoma, who had
      received at least a prior line of chemotherapy. In total, 29 patients (20 males
      and nine females) enrolled in the study received every 2 weeks, gemcitabine
      (patients #1-3 received 600 mg m(-2); patients # 4-6 received 850 mg m(-2); while
      patients # 7-29 received 1000 mg m(-2)) on the day 1, levo-folinic acid (100 mg
      m(-2)) on the days 1 and 2; 5-fluorouracil (400 mg m(-2)) in bolus injection,
      followed by a 22-h continuous infusion (800 mg m(-2)) on the days 1 and 2, and
      oxaliplatin (85 mg m(-2)), 6 h after the 5-FU bolus on day 2. The most frequent
      side effect was grade I-II haematological toxicity. In total, 28 patients were
      evaluable for response: three achieved a complete response, nine a partial
      response, 10 had a stable disease, and six progressed. The average time to
      progression and overall survival of the patients was, respectively, 7.26 and 22
      months. Our GOLF combination is well tolerated and seems promising for the
      treatment of advanced colorectal cancer.

PMID- 15150626
TI  - Quick-FLIC: validation of a short questionnaire for assessing quality of life of
      cancer patients.
AB  - A practically useful measure of quality of life should be simple and quick to
      complete. A shortened Chinese version of the Functional Living Index - Cancer
      (FLIC) was recently proposed and was called Quick-FLIC. This study aims to assess
      the measurement properties of the Quick-FLIC. A total of 190 patients who
      received care from the National Cancer Centre of Singapore completed a
      questionnaire package at baseline. Patients filled in a retest questionnaire on
      average 2 weeks after baseline to assess test-retest reliability and
      responsiveness to change. The Quick-FLIC scores correlated well with the
      Functional Assessment of Chronic Therapy - General scores (r=0.78). Patients with
      different treatment status, performance status and self-rated health had
      significantly different Quick-FLIC scores in the expected directions (ANOVA; each
      P<0.001). Internal consistency (Cronbach's alpha=0.87) and 2-week test-retest
      reliability (intraclass correlation=0.81) were also satisfactory. The measure was
      responsive to changes in health status (P<0.001). The Quick-FLIC is a valid and
      reliable measure of health-related quality of life of cancer patients. The
      shortening of established health-related quality of life instruments should be
      considered in order to reduce the burden of having patients to answer lengthy
      questionnaires.

PMID- 15150627
TI  - Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with
      paracetamol.
AB  - Gene therapy is a potential method of treating cancer with a greater degree of
      targeting than conventional therapies. In addition, therapy can be directed
      towards cells within the tumour population that are traditionally resistant to
      current treatment schedules. Horseradish peroxidase (HRP) can oxidise paracetamol
      to N-acetyl-p-benzoquinoneimine via a one-electron pathway. Incubation of human
      cells expressing HRP with 0.5-10 mM paracetamol reduced clonogenic survival, but
      had little effect on control cells. A small increase in apoptosis was seen and a
      decrease in the number of cells undergoing mitosis, consistent with reports in
      hepatocytes using higher paracetamol concentrations. The cytotoxicity was also
      seen under conditions of severe hypoxia (catalyst induced anoxia), indicating
      that the HRP/paracetamol combination may be suitable for hypoxia-targeted gene
      therapy.

PMID- 15150628
TI  - Frequent allelic deletion at the FHIT locus associated with p53 overexpression in
      squamous cell carcinoma subtype of Taiwanese non-small-cell lung cancers.
AB  - The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at
      chromosome 3p14.2, is a tumour suppressor gene involved in different tumour types
      including non-small-cell lung cancers (NSCLCs). In the current study, we examined
      for allelic deletion at the FHIT locus in 58 primary and microdissected NSCLCs,
      for which a clinicopathologic profile was available. We found a loss of 87.7% in
      heterozygosity (LOH) frequency at one or more microsatellite markers (D3S1289,
      D3S2408, D3S1766, D3S1312, D3S1600). Allelic deletion of D3S1766 was related to
      tumour histology in 10 of 11 squamous cell carcinomas (90.9%) displaying LOH
      compared with nine of 17 adenocarcinomas (52.9%; P=0.049). Besides, in the subset
      of adenocarcinomas, a higher rate of LOH at D3S1289 was observed in male (six out
      of eight, 75%) than in female patients (four out of 17, 23.5%; P=0.028). However,
      FHIT LOH was not correlated overall with a variety of clinical parameters
      including sex, smoking status, staging, lymph node metastasis and survival. These
      results indicated that the high frequency of FHIT gene disruption was important
      in the development of both squamous cell carcinomas and adenocarcinomas.
      Furthermore, there was no association between LOH at FHIT and protein expression,
      suggesting the presence of complex mechanisms of Fhit inactivation. On the other
      hand, the association between FHIT LOH and p53 protein overexpression assessment
      reached statistical significance (P=0.026), implying that common alterations
      affect the two genes in tumour progression.

PMID- 15150630
TI  - Vitamin C in health and disease.
AB  - Vitamins are essential to maintain normal metabolic processes and homeostasis
      within the body. The amount of a specific vitamin required by an individual
      varies considerably and it is influenced by such factors as body size, growth
      rate, physical activity, and pregnancy. Most vitamins are stored minimally in
      human cells, but some are stored in liver cells to a greater extent. Vitamins A
      and D, for example, may be stored in sufficient amounts to maintain an individual
      without any intake for 5 to 10 months and 2 to 4 months, respectively. However, a
      deficiency of vitamin B compounds (except vitamin B12) may be noted within days,
      and the lack of vitamin C will manifest within weeks and may result in death in 5
      to 6 months. The current recommended dietary allowance (RDA) of vitamin C is 75
      mg for woman and 90 mg for men, based on the vitamin's role as an antioxidant as
      well as protection from deficiency. High intakes of the vitamin are generally
      well tolerated, however, a Tolerable Upper Level (TUL) was recently set at 2 g
      based on gastrointestinal upset that sometimes accompanies excessive dosages.
      Several populations warrant special attention with respect to vitamin C
      requirements. These include patients with periodontal disease, smokers, pregnant
      and lactating women, and the elderly.

PMID- 15150631
TI  - The effect of fiber position and polymerization condition on the flexural
      properties of fiber-reinforced composite.
AB  - The aim of this study was to investigate the influence of the position of the
      fiber rich layer on the flexural properties of fiber-reinforced composite (FRC)
      construction. In addition, the total residual monomer content of FRC was
      quantitatively determined to find out the difference of the effectiveness of two
      types of light-curing units using liquid chromatography (HPLC). Unidirectional
      continuous E-glass FRC and hybrid particulate filler composite resins were used
      in the fabrication of test specimens. Four different positions of the FRC layer
      were used: compression, neutral, tension, and vertical side position. A three
      point bending test (ISO 10477) was performed to measure the flexural properties
      of the specimens. Position of the FRC layer had a significant effect on the
      flexural strength (p<0.001, ANOVA). Also, the type of light-curing device had an
      effect on flexural strength (p<0.001). Specimens with FRC positioned on the
      compression side showed flexural strength of approximately 250 MPa, whereas FRC
      positioned on the tension side showed strength ranging from 500 to 600 MPa. Mean
      flexural modulus with FRC placed horizontally ranged between 9-12 GPa; no
      significant difference was found between these groups. However when fiber
      reinforcement was positioned vertically, the flexural modulus raised up to 16
      GPa. Specimens with 24 vol% glass fibers contained 52% less residual monomer than
      specimens without glass fibers. The monomer content was lower in specimens
      polymerized with the curing device with higher polymerization temperature. In
      order to optimize flexural strength of low fiber volume fraction, the fibers
      should be placed at the tension side of the specimen.

PMID- 15150632
TI  - Sulphur by-product: the relationship between volatile sulphur compounds and
      dental plaque-induced gingivitis.
AB  - The purpose of this study was to evaluate the relationship between volatile
      sulphur compounds (VSC) and gingival health status, and to monitor the changes in
      VSC in early dental plaque-induced gingivitis. Using an experimental gingivitis
      model, twelve subjects between 19 and 28 years old, with a healthy gingival
      status, refrained from brushing and flossing one randomly selected half of the
      mandibular arch for two weeks. At baseline and during six subsequent
      appointments, gingival inflammation (GI), bleeding on probing (BOP), and sulfide
      levels (SUL) were measured using the Gingival Index and the Diamond Probe/Perio
      2000 System. The Spearman correlation was used to compare the relationships
      between SUL, GI, and BOP on the brushing (B) and non-brushing (NB) sides. Data on
      the NB side revealed a stronger correlation than on the B side. Wilcoxon rank sum
      was used to evaluate the differences between mean SUL, GI, and BOP scores on the
      B and NB sides over time. Results indicate that SUL were the first periodontal
      parameter to show a significant difference between sides. SUL were significantly
      higher on the NB side at 4 of the 6 data collection intervals; therefore, SUL may
      be associated with the initiation and progression of early plaque-induced
      gingivitis.

PMID- 15150633
TI  - The prevalence and relationship between periodontal disease and pre-term low
      birth weight infants at King Khalid University Hospital in Riyadh, Saudi Arabia.
AB  - The aim of this study was to examine the prevalence and relationship between
      periodontal disease and pre-term low birth weight (PLBW) among Saudi mothers at
      King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The periodontal
      status and the relative risk were also analyzed. The study consisted of 30 cases
      [infants <37 weeks and/or weighing <2.500 kilograms (kg)] and a daily random
      sample of 60 controls [> 37 weeks and/or weighing >2.500 kg]. Clinical
      periodontal indices were measured on the labor wards. Associated risk factors for
      periodontal disease and PLBW were ascertained by means of a structured
      questionnaire and maternal notes. The prevalence of the PLBW was found to be
      11.3%, and the prevalence of periodontal disease was high among the study
      population. The risk of PLBW remained high with increasing periodontal disease
      (odds ratio [OR] 4.21, 95% confident interval [CI] 1.99-8.93) despite controlling
      the other risk factors such as age, smoking, and social class. In conclusion,
      there is a correlation between periodontal disease and PLBW in KKUH.

PMID- 15150634
TI  - Storage phosphor plates: how durable are they as a digital dental radiographic
      system?
AB  - The aim of this in vitro investigation was to evaluate the durability of storage
      phosphor plates (SPPs) as a digital dental imaging system and to detect the
      factors that may contribute to possible reduced durability. A total of 140 new
      SPPs were divided into groups and exposed to the effects of the various handling
      steps during the image acquisition. An additional group of plates joined the
      existing plates in the Radiology Clinic and tested the additive effect of all
      these factors plus the effect of positioning the plates in a patient's mouth. The
      images resulting from these SPPs were regularly evaluated for the appearance of
      scratches as a sign of wear and rated by an oral radiologist using a 6 point
      scale. Although the manufacturer claims the SPPs can be used indefinitely, we
      found 95% of our plates were rendered non-diagnostic after only 50 uses. The
      manufacturer's claim for indefinite use of the SPPs seems to be questionable.

PMID- 15150635
TI  - Dental management of the Down and Eisenmenger syndrome patient.
AB  - About 40% to 50% of Down syndrome (DS) patients can have significant congenital
      heart defects such as patent ductus arteriosus, Tetralogy of Fallot, and septal
      defects. Patients with large septal defects may develop Eisenmenger syndrome
      (ES), which is defined by the cardiac septal defect and pulmonary hypertension
      coupled with a reverse right to left shunting of blood flow. DS patients that
      suffer from this condition require special considerations in the delivery of
      their dental care to prevent further medical complications or emergencies such as
      infection, cyanotic episodes, and thromboemboli. Collaboration with the
      cardiologist is also essential to ensure a complete and comprehensive pre
      operative work up. The purpose of this article is to describe the dental
      management of DS patients with ES under general anesthesia.

PMID- 15150636
TI  - Examiner agreement in the replacement decision of Class I amalgam restorations.
AB  - The aim of this study was to investigate interexaminer and intraexaminer
      agreement in the replacement decision for Class I amalgam restorations. Three
      examiners evaluated the restorations clinically and with bitewing radiographs.
      One hundred and twelve restorations were evaluated for secondary caries, body
      fracture, deficient anatomic form (contour), ditched margins, and marginal
      overhangs. After one month, the assessments were repeated by the same examiners
      under the same conditions. Cohen's Kappa analysis was used to analyze the data.
      The number of replacement decisions varied from 12 to 27 and from 6 to 14 at the
      first and second evaluations, respectively. The Kappa statistics indicated
      "moderate" to "substantial" consistency for interexaminer and intraexaminer
      agreement in the replacement decisions based on clinical and radiographical
      examinations. Restorations with deficient anatomic form and marginal overhangs
      presented the most frequent diagnostic difficulties and lead to disagreement
      among examiners. The most frequently mentioned reasons for replacement were the
      restorations had ditched margins at both clinical evaluation periods and
      secondary caries was detected during radiographical evaluations. In the absence
      of agreement among examiners, clinical and radiographic guidelines are necessary
      for replacing Class I amalgam restorations.

PMID- 15150637
TI  - The effects of water and acetone-based dentin adhesives on apical microleakage.
AB  - In this study, the aim was to assess the in vitro apical microleakage of a resin
      based sealer used with two different adhesives. Thirty nine freshly extracted
      maxillary incisors were used. The teeth were decoronated at the cemento-enamel
      junction with a water-cooled fissure bur. Chemo-mechanical debridement of the
      root canals was accomplished with the step-back technique. The smear layer was
      removed by 19% ethylenediamine tetra acetic acid (EDTA). The roots were then
      divided into three experimental groups of thirteen teeth in each. Specimens in
      group 1 were filled with gutta-percha, AH Plus sealer, and water-based adhesive
      system (Syntac Single Component). Group 2 specimens were filled with gutta
      percha, AH Plus sealer, and acetone-based dentin adhesive (Prime & Bond NT ).
      Specimens of group 3 were filled with only gutta-percha and AH Plus sealer (no
      adhesive was applied). The teeth were immersed into 2% methylene blue solution.
      Apical sealing qualities were assessed by measuring the linear dye penetration
      with a stereomicroscope. Dentin tubule penetration was observed under scanning
      electron microscopy (SEM). Results showed no statistically significant difference
      between the materials used, however, the leakage in group 2 was less than group 1
      and 3.

PMID- 15150638
TI  - Assessment of morphological changes and permeability of apical dentin surfaces
      induced by Nd:Yag laser irradiation through retrograde cavity surfaces.
AB  - The purpose of this in vitro study was to observe the morphological changes and
      apical dye penetration at apical dentin surfaces induced by Nd:YAG laser
      irradiation at different power settings with and without a laser initiator.
      Seventy five single rooted human maxillary anterior teeth were used. Following
      the establishment of the working lengths, the root canals were enlarged with step
      back technique. The apex of each root was resected 3 mm perpendicular to its long
      axis. Standard Class I cavities of 2 mm depth and 2 mm width were prepared. The
      teeth were randomly divided into five groups with fifteen teeth in each. In Group
      1, the retrograde cavity preparations were lased with Nd:YAG laser at 2 W and
      those in Group 2 preparations were lased with Nd:YAG laser at 3.2 W. In Group 3,
      the retrograde cavity surfaces were lased with Nd:YAG laser at 2 W following the
      application of India ink. Group 4 was lased with the same settings of Group 2
      after an absorbent cotton point soaked with India ink was inserted into the cut
      dentinal surfaces and the inner walls of the apical preparations. Group 5 served
      as control. Five teeth from each group were examined using scanning electron
      microscopy (SEM). The amounts of smear layer, debris, and recrystalized dentin
      present were assessed and scored. Retrograde cavities of ten teeth from each
      group were filled with amalgam to examine apical dye penetration. The teeth were
      immersed in 2% basic fuscin and kept for 48 hours. Dye penetration was evaluated
      by stereomicroscope at a magnification of X10. The results showed the usage of
      India ink with Nd:YAG laser enhanced the amount of melting and recrystalization
      of dentin and the radiation and initiator increased the leakage.

PMID- 15150639
TI  - Guided bone regeneration (GBR) on healing bone defects: a histological study in
      rabbits.
AB  - In this study, the effects of guided bone regeneration (GBR) on the healing of
      bone defects were evaluated. Resorbable membranes were placed in experimentally
      formed cavities in the right posterior tibia of 30 rabbits. Decalcified
      histological sections were evaluated using optical microscopy at 10, 20, and 30
      days after GBR. Osteocondrial bone union, active bone formation and spongiosal
      bone formation values of the GBR group are higher than the control group. It was
      found that GBR technique had a positive and accelerating influence in all phases
      of bone healing.

PMID- 15150640
TI  - The comparison of the thickness of the cementum layer in Type 2 diabetic and non
      diabetic patients.
AB  - It has been suggested diabetes plays an important role in tooth loss. Studies
      examining the periodontal structures and the alveolar bone architecture in
      diabetics have revealed some alterations. However, mechanisms responsible for
      these alterations have not been elucidated completely. Established relationships
      between the cementum layer, which is resistant to resorption, and diabetes are
      few in number. The aim of this study was to compare the thickness of the cementum
      layer in Type 2 diabetic and non-diabetic subjects in order to improve the
      understanding of dental mobility in Type 2 diabetes and its effect on tooth loss.
      A total of 46 male patients with a mean age of 61.72 +/- 5.45 yr. were included
      in this study (Type 2 diabetics, n=23; non-diabetics, n=23); undecayed. Single
      rooted premolar teeth extracted from 46 male patients were used to assess the
      alterations in the cementum layer in Type 2 diabetics. Histological preparations
      from extracted teeth were examined under light microscopy. In each tooth, the
      thickness of the cementum layer was measured by an oculometer in 4 different
      sites on the specimen with the largest pulp space including the pulp chamber and
      root canals. Statistical analyses were performed with student's t test. The
      average thickness of the cementum layer in the decalcified teeth extracted from
      non-diabetic patients was compared to the average thickness of the cementum layer
      in Type 2 diabetic patients. A significant difference was observed in every site
      of measurement between Type 2 diabetic and non-diabetic patients with regard to
      the thickness of the cementum layer (p < 0.05). The cementum layer was thicker at
      the apical part of the root and at the midpoint of the apical half, and thinner
      at the central part of the root and at the midpoint of the coronal half in Type 2
      diabetic patients.

PMID- 15150641
TI  - Occupational hazards among clinical dental staff.
AB  - Although identification of risks to dental healthcare workers has been explored
      in several industrialized nations, very little data is available from developing
      countries. This paper examines the occupational hazards present in the dental
      environment and reports survey results concerning attitudes and activities of a
      group of Nigerian dental care providers. A survey on occupational hazards was
      conducted among the clinical dental staff at the Dental Hospital of the Obafemi
      Awolowo University Teaching Hospital Complex, Ile-Ife in Osun State, Nigeria.
      Thirty eight of the forty staff responded, yielding a response rate of 95%.
      Subject ages ranged from 26 to 56 years with approximately 25% in the 31-46 year
      old bracket. All of the staff were aware of the occupational exposure to hazards,
      and the majority had attended seminars/workshops on the subject. Only five staff
      members (13.2%) owned a health insurance policy and 26 (68.4%) had been
      vaccinated against Hepatitis B infection. All dentists (24) had been vaccinated
      compared with only two non-dentists; this relationship was significant (p= 30.07,
      chi2=0.000). Fourteen members of the clinical staff (36.8%) could recall a sharp
      injury in the past six months, and the majority (71.1%) had regular contact with
      dental amalgam. Wearing protective eye goggles was the least employed cross
      infection control measure, while backache was the most frequently experienced
      hazard in 47% of the subjects. The need for Hepatitis B vaccinations for all
      members of the staff was emphasized, and the enforcement of strict cross
      infection control measures was recommended. The physical activities and body
      positions that predispose workers to backaches were identified and staff
      education on the prevention of backaches was provided.

PMID- 15150642
TI  - AAOMP case challenge: A maxillary swelling in an infant.
AB  - An asymptomatic swelling was noted in the area of the left anterior maxilla of
      this two-month old infant by the child's parents. The swelling apparently was of
      rapid onset since the pediatrician at the one-month well baby check-up did not
      note it. The swelling caused an elevation of the left alae of the nose and slight
      facial asymmetry of the upper lip.

PMID- 15150643
TI  - [Acute osseous traumatic lesions of the shoulder girdle].
AB  - Traumatic injuries to the shoulder girdle are common lesions and occur from birth
      on through the whole life. Depending on the patient's age, localization and type
      of injury change. Diagnosis of acute osseous traumatic lesions to the shoulder is
      based on evaluation of trauma mechanism, patient's examination and, as for the
      most cases, conventional radiographs. Only in certain cases additional
      radiological examinations are necessary. As a minimum, two to three images in
      different planes, anteriorposterior, lateral and axillary, are recommended in
      order to display all components of the shoulder girdle without superposition.
      Knowledge of common clinical classifications systems is necessary for exact
      diagnosis in order to permit decision on conservative or operative treatment of
      injury.

PMID- 15150644
TI  - [Conservative treatment and rehabilitation of shoulder problems].
AB  - The shoulder joint has an important influence on arm- and hand function.
      Therefore, activities of daily living, working and leisure time can be negatively
      influenced by diseases of the shoulder joint. Problems of the shoulder joint can
      be induced by muscular dysbalance and poor body posture. There is a strong
      relationship between shoulder function and body posture. Conservative treatment
      and rehabilitation of the shoulder joint aims at improving the local dysfunction
      of the shoulder joint as well as at improving function and social participation.
      Antiinflammatory and pain medication, exercise, occupational, electro-,
      ultrasound and shock wave therapy, massage, thermotherapy and pulsed
      electromagnetic fields are used as conservative treatments. Exercise therapy aims
      at improving muscular performance, joint mobility and body posture. Occupational
      therapy aims at improving functional movements for daily living and work.
      Electrotherapy is primarily used to relieve pain. Shock wave and ultrasound
      therapy proved to be an effective treatment for patients with calcific
      tendinitis. The subacromial impingement syndrome can be effectively treated by
      conservative therapy.

PMID- 15150645
TI  - [Shoulder instability].
AB  - Shoulder instability is a common clinical feature leading to recurrent pain and
      limited range of motion within the glenohumeral joint. Instability can be due a
      single traumatic event, general joint laxity or repeated episodes of microtrauma.
      Differentiation between traumatic and atraumatic forms of shoulder instability
      requires careful history and a systemic clinical examination. Shoulder laxity has
      to be differentiated from true instability followed by the clinical assessment of
      direction and degree of glenohumeral translation. Conventional radiography and CT
      are used for the diagnosis of bony lesions. MR imaging and MR arthrography help
      in the detection of soft tissue affection, especially of the glenoid labrum and
      the capsuloligamentous complex. The most common lesion involving the labrum is
      the anterior labral tear, associated with capsuloperiostal stripping (Bankart
      lesion). A number of variants of the Bankart lesion have been described, such as
      ALPSA, SLAP or HAGL lesions. The purpose of this review is to highlight different
      forms of shoulder instability and its associated radiological findings with a
      focus on MR imaging.

PMID- 15150646
TI  - [Health care costs of multiple sclerosis in Austria. Cross-sectional study
      including consideration of quality of life].
AB  - A retrospective, cross-sectional study was performed to evaluate direct and
      indirect costs related to multiple sclerosis (MS) in Austria in a representative
      cohort of patients ( n=895) with typical symptoms. Demographic, socioeconomic,
      and disease-related data including degree of disability and health-related
      quality of life as well as consumption of medical and nonmedical resources were
      recorded and mean total costs per patient and year were calculated (based on 1999
      figures). Total direct costs borne by public sources were 15,684 euro per MS
      patient per year. Overall societal costs increased disproportionately with the
      progression of the disease, from 12,990 euro per year in patients with mild
      disability to 69,554 euro per year in patients with severe disability. Increasing
      disability was reflected by substantial deterioration of health status-related
      quality of life. Direct costs of MS in Austria are similar to those in other
      countries.

PMID- 15150647
TI  - [Spontaneous intracerebral hemorrhages].
AB  - Spontaneous intracerebral hemorrhage (ICH) accounts for 8-15% of all cases of
      stroke and among patients receiving oral anticoagulants this number increases up
      to 40%. Mortality and morbidity are considerably higher in patients with ICH
      compared to patients with ischemic stroke. Large randomized controlled trials
      provide only little evidence for therapeutic strategies in patients with
      spontaneous ICH. In this review we summarize the available data and give
      recommendations on the management of spontaneous ICH.

PMID- 15150648
TI  - [Is implant removal after percutaneous iliosacral screw fixation of unstable
      posterior pelvic ring disruptions indicated?].
AB  - The aim of this study was to examine the indication for implant removal (IR)
      after percutaneous iliosacral screw fixation of unstable posterior pelvic ring
      disruptions by systematic literature analysis and clinical follow-up examination.
      Retrospective identification revealed 27 operatively stabilized patients [12
      females, mean age: 35 years, ISS 22 points (range: 14-37)] between January 1996
      and July 2001. Patient characteristics, AO classification, Hannover fracture
      scale pelvis, ISS, and DGU pelvis score points were analyzed. All cases showed a
      C-type lesion (C1:67%, C2:33%). A total of 21 patients were seen at follow-up, 12
      with and 9 without IR. In ten cases with IR, clinical outcome improved after
      surgery according to the DGU pelvis score ( p=0.001, Wilcoxon's test). These
      mostly young patients also showed a better outcome compared with those cases
      without IR. Due to the good clinical results, implant removal seems to be
      beneficial for selected individual patients, especially when pain is present.

PMID- 15150649
TI  - Mammalian cell transduction and internalization properties of lambda phages
      displaying the full-length adenoviral penton base or its central domain.
AB  - In recent years a strong effort has been devoted to the search for new, safe and
      efficient gene therapy vectors. Phage lambda is a promising backbone for the
      development of new vectors: its genome can host large inserts, DNA is protected
      from degradation by the capsid and the ligand-exposed D and V proteins can be
      extensively modified. Current phage-based vectors are inefficient and/or receptor
      independent transducers. To produce new, receptor-selective and transduction
      efficient vectors for mammalian cells we engineered lambda by inserting into its
      genome a GFP expression cassette, and by displaying the penton base (Pb) of
      adenovirus or its central region (amino acids 286-393). The Pb mediates
      attachment, entry and endosomal escape of adenovirus in mammalian cells, and its
      central region (amino acids 286-393) includes the principal receptor-binding
      motif ((340)RGD(342)). Both the phage chimerae lambda Pb and lambda Pb (286-393)
      were able to transduce cell lines and primary cultures of human fibroblasts.
      Competition experiments showed that the transduction pathway was receptor
      dependent. We also describe the different trafficking properties of lambda Pb and
      lambda Pb (286-393). Bafilomycin, which blocks endosome maturation, influenced
      the intracellular distribution of lambda Pb (286-393), but not that of lambda Pb.
      The proteasome inhibitor MG-132 improved the efficiency of lambda Pb (286-393)
      mediated transduction, but not that of lambda Pb. In summary, this work shows the
      feasibility of using lambda phage as an efficient vector for gene transfer into
      mammalian cells. We show that lambda Pb and lambda Pb (286-393) can both mediate
      receptor-dependent transduction; while only lambda Pb is able to promote
      endosomal escape and proteasome resistance of phage particles.

PMID- 15150651
TI  - [Hyperbaric oxygenation therapy following one-sided idiopathic deafness].

PMID- 15150650
TI  - The allelic variant of LAR gene promoter -127 bp T-->A is associated with reduced
      risk of obesity and other features related to insulin resistance.
AB  - Insulin resistance, which is pathogenic for type 2 diabetes (T2D), is under the
      control of largely unknown genetic determinants. LAR, a protein-tyrosine
      phosphatase which inhibits insulin signalling, is overexpressed in animal and
      human models of insulin resistance. We studied the entire sequence of the LAR
      gene by SSCP analysis and automatic DNA sequencing, with the aim of verifying
      whether its sequence variants might be associated with insulin resistance. In the
      276 bp sequence upstream of the transcriptional start site (i.e. a region we have
      identified as having basal promoter activity) a -127 bp T-->A SNP (5% frequency)
      was associated with lower body mass index (BMI) ( P=0.03), waist circumference (
      P=0.01), blood pressure ( P=0.01) and urinary albumin/creatinine ratio ( P=0.04)
      in 589 non-diabetic unrelated individuals from the Gargano region (central east
      coast of Italy). To quantify the risk for a high body weight conferred by the 
      127 T-->A SNP, the whole cohort was divided into tertiles according to the
      individual BMI. The risk of belonging to the heavier tertile, as compared to the
      leaner one, was reduced by approximately 60%. In a population from East Sicily (
      n=307), T/A genotype carriers ( n=13) showed lower triglyceride levels ( P=0.04)
      and higher insulin sensitivity as indicated by lower plasma glucose ( P=0.03) and
      serum insulin ( P=0.006) during oral glucose tolerance testing (OGTT). Promoter
      activity, studied by cDNA transfection experiments, was similar for the A and T
      alleles. In conclusion, a genetic variant of the LAR gene promoter is
      consistently associated with features of insulin resistance in two different
      Caucasian populations. Although the biological relevance of this variant has yet
      to be determined, this finding underlines the potential importance of the LAR
      gene in dysregulation of insulin sensitivity and related disorders.

PMID- 15150653
TI  - [In memoriam: Niels Ryberg Finsen].
AB  - Niels Ryberg Finsen who won the Nobel Prize in Medicine in 1903 for introducing
      phototherapy for lupus vulgaris. He was only the third laureate in medicine,
      after Emil von Behring (1901) and Ronald Ross (1902), and the first for
      outstanding achievements in the field of dermatology. Several thousand lupus
      vulgaris patients from different European countries were treated in the Medical
      Light Institute in Copenhagen, founded by Finsen, from 1896 until his death in
      1904. Until the tuberculostatic drugs were introduced in the middle of the 20th
      century, the "Finsen Exposure" was the only effective therapy of lupus vulgaris.
      The carbon arc lamp initially used by Finsen was later modified and then
      eventually replaced by the mercury quartz lamp developed by Arons. Today Finsen
      is rightly recognized as the founder of the modern dermatological phototherapy.

PMID- 15150654
TI  - [Requirements for the use of automated external defibrillators in German
      hospitals].
AB  - With an incidence of 130,000 per year, sudden cardiac death is one of the most
      frequent causes of death in Germany. Each day 350 patients die from cardiac
      arrest. Survival depends essentially on the time delay before professional help
      arrives and sufficient resuscitation measures have been started. At present,
      survival of sudden cardiac death is reported to be in the range of 5-8%. In
      preclinical conditions, many studies have already shown a successful use of
      automated external defibrillators (AED) by first responders even if they are lay
      persons. Even in large hospitals with maximum care facilities, delays before
      beginning resuscitation measures can occur which results in a dramatic reduction
      of the survival rate. Therefore, it seems reasonable to use AED in large
      hospitals. For implementation, training programmes and a nationally standardized
      documentation of resuscitation events should be promoted.

PMID- 15150652
TI  - [Eczema herpeticatum].
AB  - Patients affected by atopic dermatitis tend to develop viral infections. Probably
      the most feared complication of atopic dermatitis is eczema herpeticum, a
      disseminated infection with herpes simplex virus. A monomorphic eruption of dome
      shaped blisters, pustules and erosions in the eczematous skin lesions along with
      severe systemic illness leads to the diagnosis. The clinical diagnosis may be
      confirmed by polymerase chain reaction, viral culture, electron microscopy with
      negative staining, Tzanck test, immunofluorescence tests or serology. While
      intravenous acyclovir is still regarded as standard treatment of eczema
      herpeticum, several recently-developed antiviral drugs provide therapeutic
      options.

PMID- 15150655
TI  - Comparisons of delta13C of photosynthetic products and ecosystem respiratory CO2
      and their responses to seasonal climate variability.
AB  - This study investigated the relationship between delta13C of ecosystem
      components, soluble plant carbohydrates and the isotopic signature of ecosystem
      respired CO2 (delta13CR) during seasonal changes in soil and atmospheric moisture
      in a beech (Fagus sylvatica L.) forest in the central Apennine mountains, Italy.
      Decrease in soil moisture and increase in air vapour pressure deficit during
      summer correlated with substantial increase in delta13C of leaf and phloem sap
      soluble sugars. Increases in delta13C of ecosystem respired CO2 were linearly
      related to increases in phloem sugar delta13C (r2=0.99, P<or=0.001) and leaf
      sugar delta13C (r2=0.981, P<or=0.01), indicating that a major proportion of
      ecosystem respired CO2 was derived from recent assimilates. The slopes of the
      best-fit lines differed significantly (P<or=0.05), however, and were about 0.86
      (SE=0.04) for phloem sugars and about 1.63 (SE=0.16) for leaf sugars. Hence,
      changes in isotopic signature in phloem sugars were transferred to ecosystem
      respiration in the beech forest, while leaf sugars, with relatively small
      seasonal changes in delta13C, must have a slower turnover rate or a significant
      storage component. No significant variation in delta13C was observed in bulk dry
      matter of various plant and ecosystem components (including leaves, bark, wood,
      litter and soil organics). The apparent coupling between the delta13C of soluble
      sugars and ecosystem respiration was associated with large apparent isotopic
      disequilibria. Values of delta13CR were consistently more depleted by about 4 per
      thousand relative to phloem sugars, and by about 2 per thousand compared to leaf
      sugars. Since no combination of the measured pools could produce the observed
      delta13CR signal over the entire season, a significant isotopic discrimination
      against 13C might be associated with short-term ecosystem respiration. However,
      these differences might also be explained by substantial contributions of other
      not measured carbon pools (e.g., lipids) to ecosystem respiration or
      contributions linked to differences in footprint area between Keeling plots and
      carbohydrate sampling. Linking the seasonal and inter-annual variations in carbon
      isotope composition of carbohydrates and respiratory CO2 should be applicable in
      carbon cycle models and help the understanding of inter-annual variation in
      biospheric sink strength.

PMID- 15150656
TI  - Photoinhibition in seedlings of Fraxinus and Fagus under natural light
      conditions: implications for forest regeneration?
AB  - Ash (Fraxinus excelsior L.) and beech (Fagus sylvatica L.) seedlings were grown
      in the field under three levels of natural light: (1) open, (2) gap and (3)
      shade. Light acclimation of photosynthesis was characterized by means of
      modulated chlorophyll a fluorescence of intact leaves and growth parameters were
      measured at the end of the growing season. Measurements of maximum photochemical
      efficiency (Fv/Fm) of dark-adapted leaves at intervals through the day showed
      that ash had a higher Fv/Fm than beech in open and gap plots but not in shade
      plots. This indicated a larger build-up of photoinhibition in beech under gap and
      open conditions. Steady-state light response curves of the operating efficiency
      of PSII (F'q/F'm), the electron transport rate (ETR) and the photochemical
      efficiency factor (F'q/F'v) showed greater variability across light treatments in
      ash than in beech. Both species exhibited similar responses of non-photochemical
      quenching (NPQ) to light. When the data were normalized to the mean maximum
      irradiance in the growth environment, all photochemical parameters showed a
      reduction in variation across treatments, indicating that light acclimation in
      the two species occurred primarily through adjustments in rates of
      photochemistry. Adjustments in thermal heat dissipation were small in both
      species. This pattern was stronger in ash, suggesting a greater degree of
      phenotypic plasticity in photosynthetic capacity in this earlier successional
      species. Contrary to our expectations, the build-up of photoinhibition in beech
      did not appear to have a negative effect on total biomass accumulation relative
      to ash.

PMID- 15150658
TI  - Successful endoscopic drainage of a pancreatic pseudocyst in a 17-month-old boy.
AB  - Pancreatic pseudocysts (PPCs) develop in 10% to 30% of children with acute
      pancreatitis. PPCs that impinge on neighbouring structures, cause pain, or fail
      to undergo spontaneous resolution must be drained. Surgery and percutaneous
      aspiration are the most widely used techniques for draining PPCs. We successfully
      performed an endoscopic drainage in a 17-month-old boy. A nasobiliary catheter
      was inserted via the gastric wall under endoscopic guidance to drain an 8 cm PPC
      of unknown origin responsible for pain, ascites, and displacement of the stomach
      with vomiting. The cyst collapsed. Eighteen months later, the child had no
      symptoms or abnormalities by laboratory testing or ultrasonography. Whereas
      endoscopic drainage is widely used to treat PPC in adults, only five paediatric
      cases have been published. CONCLUSION: as compared to surgery, endoscopic
      drainage has provided similar efficacy and recurrence rates, with less morbidity.

PMID- 15150657
TI  - Experience with platinum-based and high-dose chemotherapy in patients with
      gestational trophoblastic disease: possible implications for future management.
AB  - PURPOSE: Despite the similarities between the chemotherapeutic management of
      advanced gestational trophoblastic disease (GTD) and ovarian germ cell tumors,
      important differences exist between the malignancies, particularly in the use of
      cisplatin. METHODS: Three patients with persistent or recurrent GTD cared for at
      the Cleveland Clinic received a high-dose chemotherapy program (with stem cell
      support), one as management for etoposide-associated acute leukemia resulting
      from her "standard dose" treatment program. RESULTS: While the indications for
      use of a dose-intensive strategy, and the ultimate clinical course, differed in
      the three patients, collectively these cases raise relevant questions regarding
      optimal management of high risk and recurrent GTD. CONCLUSION: The experience
      represented in this report support the earlier use of cisplatin-based
      chemotherapy in the management of high-risk and recurrent GTD, and the possible
      administration of a high-dose chemotherapy program in the rare patient who recurs
      following "standard dose" platinum-based treatment.

PMID- 15150659
TI  - Pneumococcal peritonitis mimicking acute appendicitis.

PMID- 15150661
TI  - Heat and mass transfer from a baby manikin: impact of a chemical warfare
      protective bag.
AB  - A chemical warfare (CW) protective bag for babies, younger than 1 year, has been
      evaluated in respect of thermal load. Heat and water vapour dissipating from the
      baby make the climate in the protective bag more demanding than outside. The
      thermal strain on a baby was estimated from heat and mass transfer data using an
      electrically heated baby manikin and a water-filled tray. Furthermore, a
      theoretical baby model was developed based on relations valid for heat and mass
      transfer rates from a cylinder and flat surface. Convective and radiative (dry)
      and evaporative heat transfer coefficients calculated from this model agreed well
      with the measured values. The maximum heat dissipation from a baby was calculated
      for combinations of air temperatures (22-30 degrees C) and relative humidities
      (70-90% rh). The results indicate that a naked baby can dissipate about 100% more
      heat than is produced during basal conditions when the bag is ventilated (70 1
      min(-1)) and the ambient climate is 30 degrees C and 90% rh. If the ventilation
      rate is 40 1 min(-1), the margin is reduced to 50%. Clothing reduces the margin
      further. Ventilating the bag with 70 1 min(-1), a dressed baby can dissipate only
      10-20% more heat than is produced during basal conditions in a climate (27
      degrees C and 80% rh) that is obtained in a crowded shelter after about 24 h of
      occupation.

PMID- 15150660
TI  - Hyperthermia and maximal oxygen uptake in men and women.
AB  - To compare the effect of hyperthermia on maximal oxygen uptake (VO2max) in men
      and women, VO2max was measured in 11 male and 11 female runners under seven
      conditions involving various ambient temperatures (Ta at 50% RH) and preheating
      designed to manipulate the esophageal (Tes) and mean skin (Tsk) temperatures at
      VO2max. The conditions were: 25 degrees C, no preheating (control); 25, 35, 40,
      and 45 degrees C, with exercise-induced preheating by a 20-min walk at
      approximately 33% of control VO2max; 45 degrees C, no preheating; and 45 degrees
      C, with passive preheating during which Tes and Tsk were increased to the same
      degree as at the end of the 20-min walk at 45 degrees C. Compared to VO2max (l x
      min(-1)) in the control condition (4.52+/-0.46 in men, 3.01+/-0.45 in women),
      VO2max in men and women was reduced with exercise-induced or passive preheating
      and increased Ta, approximately 4% at 35 degrees C, approximately 9% at 40
      degrees C and approximately 18% at 45 degrees C. Percentage reductions (7-36%) in
      physical performance (treadmill test time to exhaustion) were strongly related to
      reductions in VO2max (r=0.82-0.84). The effects of hyperthermia on VO2max and
      physical performance in men and women were almost identical. We conclude that men
      and women do not differ in their thermal responses to maximal exercise, or in the
      relationship of hyperthermia to reductions in VO2max and physical performance at
      high temperature. Data are reported as mean (SD) unless otherwise stated.

PMID- 15150662
TI  - Glove thermal insulation: local heat transfer measures and relevance.
AB  - When exposed to cold, the hands need to be protected against heat loss not only
      in order to reduce thermal discomfort, but also to keep their efficiency.
      Although gloves are usually the most common protection, their thermal insulation
      is generally unknown. The aim of this study was to measure the heat losses from a
      gloved hand with a special interest in local variations. Using a calorimetric
      hand placed in a cold box, several types of gloves were tested. The results
      indicated that depending on the glove and on the area covered the heat loss
      reduction may vary from almost 60% to 90%. When the least efficient pair of
      gloves was excluded, heat exchange coefficients varied from 1.8 to 4.8 W/m2 per
      degrees C for the palm and from 4.2 to 6.2 W/m2 per degrees C for the back of the
      hand. The three medium fingers seemed to be equally treated, with a heat exchange
      coefficient variation of 6.3-9.0 W/m2 per degrees C. The thumb and the little
      finger, which require better insulation, exhibited higher local heat transfer
      coefficients of 8.3-12.7 W/m2 per degrees C. Some practical aspects are evoked.

PMID- 15150663
TI  - Hepato-cerebral syndrome: genetic and pathological studies in an infant with a
      dGK mutation.
AB  - Focal spongy degeneration of the white matter and Purkinje cell loss were the
      neuropathological hallmarks in an infant with hepato-cerebral syndrome and a 4-bp
      GATT duplication (nucleotides 763-766) in exon 6 of the dGK gene. Liver disease
      became manifest in the first months of life and was followed by progressive
      cirrhosis and death at 31 months. Neurological symptoms appeared later and were
      mild, in agreement with the limited brain pathology. Molecular analysis of the
      dGK gene should be performed in infants with cirrhosis even in the absence of CNS
      involvement.

PMID- 15150665
TI  - [Status of rendering an expert opinion following the changes in the German
      traffic legislation].
AB  - The new traffic legislation in Germany ("FeVAndV") solves at least the most
      urgent problems for the ophthalmological driver's license assessment which were
      present in the old, preceding regulations ("FeV"). Many suggestions of the
      traffic committee of the German Ophthalmological Society ("DOG") were taken into
      consideration. As expected, the recommendations of the traffic committee
      concerning an obligatory test of mesopic vision were not adopted into the new
      legislation. We still have the unacceptable situation that on the one hand the
      European legislation demands an obligatory test of mesopic vision in suspected
      candidates and the German legislation even has the necessary key note for a ban
      on night driving ("05.01"). On the other hand, testing of mesopic vision is not
      considered on a regular basis in the new German regulations. This is not
      acceptable from an ophthalmological point of view.

PMID- 15150666
TI  - Fixed-flexion radiography of the knee provides reproducible joint space width
      measurements in osteoarthritis.
AB  - The validity of a non-fluoroscopic fixed-flexion radiographic acquisition and
      analysis protocol for measurement of joint space width (JSW) in knee
      osteoarthritis is determined. A cross-sectional study of 165 patients with
      documented knee osteoarthritis participating in a multicenter, prospective study
      of chondroprotective agents was performed. All patients had posteroanterior,
      weight-bearing, fixed-flexion radiography with 10 degrees caudal beam angulation.
      A specially designed frame (SynaFlexer) was used to standardize the positioning.
      Minimum medial and lateral JSW were measured manually and twice by an automated
      analysis system to determine inter-technique and intra-reader concordance and
      reliability. A random subsample of 30 patients had repeat knee radiographs 2
      weeks apart to estimate short-term reproducibility using automated analysis.
      Concordance between manual and automated medial JSW measurements was high
      (ICC=0.90); lateral compartment measurements showed somewhat less concordance
      (ICC=0.72). There was excellent concordance between repeated automated JSW
      measurements performed 6 months apart for the medial (ICC=0.94) and lateral
      (ICC=0.86) compartments. Short-term reproducibility for the subsample of 30 cases
      with repeat acquisitions demonstrated an average SD of 0.14 mm for medial JSW
      (CV=4.3%) and 0.23 mm for lateral JSW (CV=4.0%). Fixed-flexion radiography of the
      knee using a positioning device provides consistent, reliable and reproducible
      measurement of minimum JSW in knee osteoarthritis without the need for concurrent
      fluoroscopic guidance.

PMID- 15150667
TI  - An unusual cause of hydrocephalus: aqueductal developmental venous anomaly.
AB  - Vascular malformations are infrequent causes of aqueductal stenoses,
      developmental venous anomaly (DVA) being the rarest among them. DVAs, also known
      as venous angiomas, are congenital in origin and characterized by dilatation of
      vessels in the superficial and deep venous system. Although they are usually
      clinically silent, they can be complicated by hemorrhage, seizures and neurologic
      deficits. Herein, we report MR imaging findings of a 7-year-old girl whose
      hydrocephalus was due to an abnormal vein coursing through the aqueduct.

PMID- 15150668
TI  - Radiofrequency ablation of renal tumors.
AB  - Percutaneous thermal ablation is increasingly applied in the therapy of renal
      tumors. Various techniques are available, allowing a safe and accurate therapy of
      renal tumors either using hyperthermia such as radiofrequency ablation (RFA),
      laser-induced thermotherapy (LITT) and microwave ablation (MW) or by hypothermia
      (cryoablation). As thermal ablation is a minimally invasive and nephron-sparing
      procedure, it is ideally suited for patients with a single kidney, multiple
      tumors or contraindications for resective surgery. Although cryotherapy is the
      most extensively studied technique, RFA has become the most accepted thermal
      ablation technique over the last years. Modern RFA probes allow ablation volumes
      between 2 and 5 cm in diameter. A major advantage of RFA is the ability to avoid
      tract bleeding and tumor seeding by coagulating the puncture channel during RF
      probe withdrawal. The increasing number of clinical reports on RFA of the kidney
      show the promising potential of renal RFA for minimally invasive tumor treatment.
      Due to its technical benefits, RFA seems to be advantageous when compared to
      cryoablation or laser ablation. However, there are no long-term follow-up or
      comparative data proving an equal effectiveness to surgery.

PMID- 15150669
TI  - Investigation of the basis of virulence in serotype A strains of Cryptococcus
      neoformans from apparently immunocompetent individuals.
AB  - Cryptococcus neoformans serotype A strains commonly infect immunocompromised
      patients to cause fungal meningitis. To understand the basis of serotype A
      cryptococcal infections in apparently immunocompetent patients, we tested two
      hypotheses: the strains were naturally occurring hypervirulent pkr1 (PKA
      regulatory subunit) mutants, or the strains were hybrids with C. neoformans var.
      gattii strains that normally infect immunocompetent individuals. Analysis of
      clinical isolates obtained from apparently immunocompetent individuals from three
      continents revealed that none were pkr1 mutants, but several exhibited phenotypes
      consistent with perturbations in cAMP signaling. Additionally, none of the
      strains were unusual hybrids with gattii strains. Except for one strain that was
      an AD hybrid, all others were serotype A (var. grubii) isolates. Taken together,
      our findings indicate that the ability of these clinical isolates to infect
      apparently normal individuals may be attributable to mutations other than pkr1
      and/or underlying immune system impairment in patients.

PMID- 15150670
TI  - The yeast phosphotyrosyl phosphatase activator protein, yPtpa1/Rrd1, interacts
      with Sit4 phosphatase to mediate resistance to 4-nitroquinoline-1-oxide and UVA.
AB  - We previously reported the isolation of mutants hypersensitive to the genotoxic
      agent 4-nitroquinoline-1-oxide, a potent inducer of oxidative stress. One of the
      mutants was defective in a gene designated yPTPA1, encoding a protein related to
      the human phosphotyrosyl phosphatase activator hPTPA, which is believed to play a
      role in activating the serine/threonine phosphatase PP2A. Yeast yptpa1Delta
      mutants are also sensitive to the UVA component of sunlight known to produce
      reactive oxygen species, suggesting a role for yPtpa1 in oxidative stress
      response. We now report the characterization of another 4-nitroquinoline-1-oxide
      sensitive mutant, EBY20. We show that this mutant is defective in the SIT4 gene
      encoding a catalytic subunit of the PP2A phosphatases and that sit4Delta mutants
      exhibit hypersensitivity to 4-nitroquinoline-1-oxide and UVA, but not to UVC at
      254 nm. Like the yptpa1Delta mutants, sit4Delta mutants are also defective in the
      repair of 4-nitroquinoline-1-oxide-induced DNA lesions. Genetic analysis revealed
      that both yPtpa1 and Sit4 function in the same pathway to protect cells against
      the lethal effects of 4-nitroquinoline-1-oxide and UVA. Moreover, we demonstrate
      that yPtpa1-affinity columns specifically retain Sit4, confirming a previous
      report that these two proteins indeed belong to a complex. Cellular localization
      studies using GFP-tagged proteins reveals that yPtpa1 is localized to the
      cytoplasm and the nucleus, while the Sit4 protein shows an intense staining spot
      in the cytoplasm and diffused staining in this organelle. We suggest that the
      yPtpa1-Sit4 complex may participate in a novel mechanism that mediates repair of
      oxidative DNA damage caused by 4-nitroquinoline-1-oxide and UVA.

PMID- 15150671
TI  - Plasma and cerebrospinal fluid pharmacokinetics of rebeccamycin (NSC 655649) in
      nonhuman primates.
AB  - PURPOSE: The rebeccamycins, indolocarbazole topoisomerase I poisons originally
      discovered in actinomycetes, have shown activity in vitro against a range of
      adult and pediatric tumors. The derivative NSC 655649 (diethylaminoethyl analog
      of rebeccamycin, or DEAE rebeccamycin) is currently undergoing early-phase human
      studies and has shown some signs of antitumor activity. We studied the plasma and
      cerebrospinal fluid (CSF) pharmacokinetics of NSC 655649 after systemic
      administration in a nonhuman primate model that is predictive of anticancer drug
      behavior in humans. DESIGN: A dose of 400 mg/m2 was infused over 1 h to three
      rhesus monkeys. Serial blood and CSF samples were collected. Rebeccamycin
      concentrations were measured by high-pressure liquid chromatography.
      Pharmacokinetic analysis was performed using compartmental and noncompartmental
      methods. RESULTS: A two-compartment or three-compartment model described
      rebeccamycin pharmacokinetics in plasma adequately. In two animals, the three
      compartment model provided a better fit, and in one animal, the two-compartment
      model was better. The terminal half-life was 730+/-410 min, the AUC was 3130+/
      425 microM min, and the clearance was 190+/-25 ml/min/m2. Rebeccamycin was below
      the limit of quantitation in all CSF samples. The animals had some nausea and
      agitation during and shortly after the infusion that responded to treatment with
      prochlorperazine or diazepam. Otherwise, rebeccamycin was well tolerated with
      minimal toxicity. CONCLUSION: Rebeccamycin penetrates poorly into the CSF
      following an intravenous infusion. Therefore, systemically administered
      rebeccamycin is unlikely to be an important agent for the treatment of
      leptomeningeal tumors. Because the drug is associated with local irritation at
      injection sites, it is not an ideal candidate for development as an intrathecal
      agent. However, the role of rebeccamycin in the treatment of parenchymal brain
      tumors should be determined in clinical trials.

PMID- 15150672
TI  - Usefulness of 18FDG/13N-ammonia PET imaging for evaluation of the cardiac damage
      in Churg-Strauss syndrome.

PMID- 15150673
TI  - Myocardial gated SPECT phantom.

PMID- 15150675
TI  - Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in
      neuroendocrine tumours.
AB  - Somatostatin receptors are over-expressed in many tumours, mainly of
      neuroendocrine origin, thus enabling treatment with somatostatin analogues.
      Almost a decade of clinical experience of receptor radionuclide therapy with the
      analogue (90)Y-[DOTA](0)-Tyr(3)-octreotide [(90)Y-DOTATOC] has now been obtained
      at a few centres of excellence. This review reports on the present state of the
      art of receptor radionuclide therapy and discusses new perspectives.

PMID- 15150676
TI  - Soft tissue aneurysmal bone cyst.
AB  - A soft tissue aneurysmal bone cyst located in the right gluteus medius of a 21
      year-old man is reported. On conventional radiography, the lesion demonstrated a
      spherically trabeculated mass with a calcific rim. On CT scan, it showed a well
      organized peripheral calcification resembling a myositis ossificans. On MRI, it
      presented as a multilocular, cystic lesion with fluid-fluid levels. The lesion
      had no solid components except for intralesional septa. Although findings on
      imaging and histology were identical to those described in classical aneurysmal
      bone cyst, diagnosis was delayed because of lack of knowledge of this entity and
      its resemblance to the more familiar post-traumatic heterotopic ossification
      (myositis ossificans).

PMID- 15150677
TI  - Angiogenic factors in serum of patients with testicular germ cell tumours.

PMID- 15150678
TI  - Spontaneous regression of two supraophthalmic internal cerebral artery aneurysms
      following flow pattern alteration.
AB  - We report on a patient with fibromuscular dysplasia who presented with a right
      sided giant calcified cavernous internal carotid artery (ICA) aneurysm and two
      additional supraophthalmic ICA aneurysms. Endovascular closure of the right ICA
      using detachable balloons was performed with collateralisation of the right
      hemisphere via the right-sided posterior communicating and the anterior
      communicating arteries. Repeat angiography after 6 months demonstrated
      spontaneous complete regression of the two supraophthalmic aneurysms, although
      the parent vessel was still perfused. In comparison to the former angiography,
      the flow within the parent vessel was reversed due to the proximal ICA balloon
      occlusion. MRI demonstrated that the aneurysms were not obliterated by thrombosis
      alone, but showed a real regression in size. This case report demonstrates that
      changes in cerebral hemodynamics potentially lead to plastic changes in the
      vessel architecture in adults and that aneurysms can be flow-related, even if not
      associated with high flow fistulas or arteriovenous malformations, especially in
      cases with an arterial wall disease.

PMID- 15150679
TI  - Pharmacokinetic/pharmacodynamic modelling of effects of dexamethasone and
      prednisolone in combination with endogenous cortisol on lymphocyte counts and
      systemic markers of bone turn over and inflammation in healthy and asthmatic men.
AB  - OBJECTIVE: To compare potency and efficacy of dexamethasone (DEXA) and
      prednisolone (PRED) in assumed equipotent doses in combination with endogenous
      cortisol, using lymphocyte counts, plasma osteocalcin (OC), and eosinophilic
      cationic protein (ECP) as effect variables and to evaluate potential differences
      between healthy subjects and asthmatic patients. METHODS: Eight healthy subjects
      and six asthmatic patients who had stopped taking their regular inhaled
      glucocorticosteroid treatment (ICS) for 1 week, were given an IV bolus of DEXA
      and PRED in assumed equipotent doses of 2.0 mg and 12.5 mg, respectively, on
      separate occasions, in combination with subcutaneously injected granulocyte
      colony-stimulating factor (G-CSF) as a stimulant for ECP production. Plasma
      levels of DEXA, PRED, cortisol and effect variables were determined over 25 h and
      pharmacokinetic-pharmacodynamic (PK-PD) modelling was performed. RESULTS:
      Baseline cortisol concentration was lower in patients than in healthy subjects.
      Both of the exogenous glucocorticoids (GCs) diminished cortisol production. In
      the healthy subjects, the cortisol production remained suppressed for the full
      duration of the study day after DEXA but not after PRED. In the asthmatic
      patients though, the reappearance of the endogenous production of cortisol was
      seen after both DEXA and PRED. The E(max) values for lymphocyte counts and OC
      showed that cortisol acted as partial, and DEXA and PRED as full agonists. The
      observed responses of DEXA and PRED suppressing cortisol, OC and lymphocyte
      counts were all of the same relative order of magnitude, in accordance with the
      estimated PD parameters. However, cortisol was estimated to have very little
      effect on ECP and modelling further predicted that DEXA and PRED were only
      partial agonists for this effect, without a difference between healthy and
      asthmatic subjects. Yet, in healthy subjects, the area under the concentration
      time curves (AUCs) indicated unexpectedly that ECP was only suppressed after PRED
      and not after DEXA, while in patients it was suppressed after both GCs. The rank
      order of potency on lymphocyte counts, OC and ECP was DEXA>PRED>cortisol,
      although the different relative potencies of the three GCs involved were not the
      same for all of the three effect variables and differences were also found
      between healthy and asthmatic subjects. CONCLUSION: PK-PD modelling studies of
      GCs demonstrated not only differences in potency of DEXA and PRED on the measured
      systemic markers, but also different potencies per target tissue and differences
      between healthy and asthmatic men. The effects caused by the achieved blood
      concentrations of DEXA and PRED, expressed as AUCs of the effect variables, were
      in accordance with their respective E(max) values in case of the lymphocytes and
      OC but not for ECP.

PMID- 15150680
TI  - Thrombocytopenia and fatality associated with olanzapine.

PMID- 15150681
TI  - Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and
      methylmercury in cell lines of neural origin.
AB  - Mercury and aluminum are considered to be neurotoxic metals, and they are often
      connected with the onset of neurodegenerative diseases. In this study, mercuric
      mercury, methylmercury and aluminum were studied in three different cell lines of
      neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis
      induced by the metals were measured after various incubation times. SH-SY5Y
      neuroblastoma, U 373MG glioblastoma, and RPE D407 retinal pigment epithelial
      cells were subcultured to appropriate cell culture plates and 0.01-1,000 microM
      concentrations of methylmercury, mercuric and aluminum chloride were added into
      the growth medium. In the assay measuring the mitochondrial dehydrogenase
      activity, WST-1, the cultures were exposed for 15 min, 24 or 48 h before
      measurement. Cells were allowed to recover from the exposure in part of the
      study. Apoptosis induced by the metals was measured after 6-, 24- and 48-h
      exposure times with the determination of activated caspase 3 enzyme.
      Mitochondrial assays showed a clear dose-response and exposure time-response to
      the metals. The most toxic was methylmercury (EC50 ~0.8 microM, 48 h), and the
      most sensitive cell line was the neuroblastoma cell line SH-SY5Y. Furthermore,
      there was marked mitochondrial activation, especially in connection with aluminum
      and methylmercury at low concentrations. This activation may be important during
      the initiation of cellular processes. All the metals tested induced apoptosis,
      but with a different time-course and cell-line specificity. In microscopic
      photographs, glioblastoma cells formed fibrillary tangles, and neuroblastoma
      cells settled along the fibrilles in cocultures of glial and neuronal cell lines
      during aluminum exposure. The study emphasized the toxicity of methylmercury to
      neural cells and showed that aluminum alters various cellular activities.

PMID- 15150682
TI  - Transplacental passage of Pt after treatment with the new triamine complex cis
      diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chloride platinum
      (II) monohydrochloride monohydrate.
AB  - Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chloride platinum
      (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex
      synthesized starting from cisplatin and procaine hydrochloride, characterized by
      a good antitumor activity coupled with low toxic effects and able to impair
      prenatal development of mice but at doses outside or just in the upper range of
      therapeutic doses. In the present paper the transplacental passage of DPR-derived
      Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after
      ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated
      with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to
      cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of
      gestation the concentration of DPR- and cisplatin-derived Pt increased up to the
      highest fetal concentrations detected on day 16. On day 18 the concentration of
      Pt decreased. Most importantly, on days 13-18 of pregnancy cisplatin-derived Pt
      was always significantly higher than that assayed after DPR administration. In
      addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher
      when dams were treated with cisplatin (AUC(0.5-24)= 3.40 vs. 4.95 microg.h/g).
      Finally, it is worth noting that serum decay of Pt after DPR or cisplatin
      administration in adult female mice was similar with AUC0.13-2h s of 7.5 and 6.6
      microg.h/ml, respectively. When we determined the concentration of Pt into the
      main organs of fetuses from dams treated with either DPR or cisplatin on day 18
      of gestation, we observed a different organ distribution. In fact, while the
      concentration of DPR-derived Pt was greater in the heart (1.08+/-0.30 vs. 0.78 +/
      0.35 microg/g, p <0.10), an opposite situation was found in the kidney (0.51+/
      0.20 vs. 0.69 +/- 0.22 microg/g, p <0.05). In conclusion, our data show that DPR
      may pass through the placenta with an efficiency significantly lower than that of
      cisplatin. This finding may represent one of the possible causes of the lower
      embryotoxic/teratogenic effect of DPR as compared to cisplatin.

PMID- 15150684
TI  - [Surface characterization of Al2O3-blasted titanium implants in total hip
      arthroplasty].
AB  - INTRODUCTION: Shot peening and grit blasting techniques are used in several
      surface modifications for producing hip endoprostheses. Corund blasting
      techniques using highly pure Al2O3 particles to create a rough surface of
      titanium implants in cementless total hip arthroplasty achieve better
      osteointegration. An increasing number of publications in maxillofacial surgery
      and orthopedic surgery show that there is a significant contamination on corund
      blasted surfaces. The latest research studies reported an effect of contaminant
      particles on early failure of endoprostheses associated with third body wear. The
      aim of our work was to evaluate the amount and particle size of Al2O3 on the
      implant surface. MATERIAL AND METHOD: The surface of four different geometries
      (five parts each, ARR titanium acetabular reinforcement ring, anisotropic Vektor
      cup, Vektor titanium stem and modular MRP Titan stem) were analyzed with respect
      to Al2O3 particles. Grit blasting was performed with Al2O3 particles, Alodur
      SWSK, Fa. Treibacher. Field emission scanning electron microscopy (LEO 1525) was
      used for the detection of the Al2O3 particles at the implant surface with a
      backscattered electron detector. The particle size distribution as well as the
      average area of the covered surface was calculated with image analyzing software
      (analySIS, Soft Imaging System GmbH). RESULTS: The surface of the anisotropic
      Vektor cup was contaminated at an average of 41.7+/-4.9%, the Vektor titanium
      stem at an average of 33.3+/-4.7%, the (MRP) Titan stem at an average of 30.6+/
      4.2%, and the ARR titanium acetabular reinforcement ring at an average of 23.2+/
      1.6 with Al2O3 particles over the whole surface orientated to the bone.
      DISCUSSION: The results of this study clearly show that there is contamination of
      rough titanium surfaces with Al2O3 particles at an unexpectedly high percentage.
      With respect to third body wear in total hip arthroplasty, further studies are
      necessary to minimize contamination of roughened surfaces and maintain sufficient
      roughness for osteointegration.

PMID- 15150683
TI  - Heparin-induced thrombocytopenia in paediatrics: clinical characteristics,
      therapy and outcomes.
AB  - OBJECTIVE: Reports on heparin-induced thrombocytopenia (HIT) in paediatrics are
      confined to isolated case reports. The objective was to systematically combine
      the published data. DESIGN AND SETTING: Cases were identified by MEDLINE search
      and review of bibliographies. PATIENTS: We included subjects reported with HIT,
      collecting patient demographics, clinical and laboratory characteristics,
      therapeutic regimens and outcomes. MEASUREMENTS AND RESULTS: Reports on 70
      patients were retrieved. In a majority of children, HIT occurred during
      hospitalisation in a paediatric ICU. In most patients, the typical onset pattern
      was reported, although rapid-onset-pattern HIT occurred in some. The median
      platelet-count nadir was 54x10(9)/l; 11% of reported patients had nadirs in the
      normal range. Clinical symptoms included isolated thrombocytopenia and solitary
      or combined venous, arterial and intracardiac thromboembolism, sometimes catheter
      related. Pulmonary embolism and major bleeding were rarely described.
      Confirmatory functional or antigenic testing of HIT antibodies showed a similar
      cumulative sensitivity of about 88%. An unfavourable outcome (death/limb
      amputation) was reported in 42.1% of patients without therapy and in 18% of
      patients treated with danaparoid, lepirudin, or argatroban. CONCLUSIONS: HIT in
      children mainly occurs in paediatric intensive care with diagnostic features and
      outcomes similar to those seen in adults. HIT cannot be ruled out based on normal
      platelet counts or occurrence after fewer than 5 days of heparin exposure.
      Children should be presumed to suffer from HIT based on clinical grounds and
      treated accordingly (immediate heparin withdrawal and alternative
      anticoagulation). Alternative anticoagulation with danaparoid, lepirudin and
      argatroban appears to improve outcomes.

PMID- 15150685
TI  - [The use of regional anesthesia in orthopedics].
AB  - Regional anesthesia has its place in the perioperative pain management of
      orthopedic patients. A reduction in postoperative mortality and morbidity with
      regional anesthesia is acknowledged for subsets of patient populations. Single
      shot and continuous applications are techniques for providing regional analgesia.
      Continuous infusion of local anesthetics with catheter techniques provides for
      uninterrupted postoperative analgesia. The combination of regional and general
      anesthesia reduces the consumption of systemic anesthetics. The side effects of
      opioid therapy are thereby reduced. The inhibition of intraoperative stress
      reaction, especially with epidural anesthesia, helps to prevent or lower unwanted
      metabolic changes. Patient contentment with analgesic quality differs with the
      technique with which the regional anesthesia is applied (PDA, PCEA, IVRA,
      peripheral block, i.a. injection), and the medication (LA, opioid) used.

PMID- 15150687
TI  - [Devil's claw extract as an example of the effectiveness of herbal analgesics].
AB  - Preparations from devil's claw differ in their content of active ingredients as
      assessed by the quantity of harpagoside present. The harpagoside content in the
      daily dose of Doloteffin (extraction solvent water) is double that of
      preparations extracted with 60% ethanol. Only preparations with proven
      effectiveness for painful lower back or arthrotic pain are an attractive
      alternative to synthetic analgesics, and are of substantial benefit in the
      treatment of chronic pain. From an evidence based view, extract with at least 50
      mg harpagoside in the daily dose should be recommended for the treatment of pain.
      Treatment with devil's claw extract is associated with a lower risk of adverse
      events than treatment with synthetic analgesics, and may contribute in the
      majority of patients to the relief of pain.

PMID- 15150686
TI  - [Drug therapy in complex regional pain syndrome type I].
AB  - Pharmacologic treatment options for complex regional pain syndrome (CRPS) type I
      are discussed and drug effectiveness is graded according to the level of evidence
      available. Various drug strategies in the treatment of CRPS type I, i.e. NSAIDs,
      corticosteroids, free radical scavengers, antidepressants, anticonvulsants, local
      anesthetics, opioid analgesics, clonidine, capsaicin, NMDA receptor antagonists,
      calcitonin, bisphosphonates, GABA(B)-agonists, alpha-blockers, IVRA
      (bretylium/ketanserin), IVRA (clonidine), IVRSB, local anesthetics sympathetic
      blockade, GLOA and iloprost are discussed.

PMID- 15150688
TI  - [Characterization of custom-made biomaterials containing antibiotics].
AB  - The aim of this study was to evaluate the quality of custom-made antibiotic
      carriers which are produced for hospitals in a central service laboratory. These
      sterile products, made according to antibiogram, showed quality parameters which
      are comparable with commercially available products in terms of antibiotic
      release and other relevant properties.

PMID- 15150689
TI  - Response to Chiasson et al.: Acarbose for the prevention of Type 2 diabetes,
      hypertension and cardiovascular disease in subjects with impaired glucose
      tolerance: facts and interpretations concerning the critical analysis of the STOP
      NIDDM Trial data.

PMID- 15150690
TI  - In silico mapping of quantitative trait loci in maize.
AB  - Quantitative trait loci (QTL) are most often detected through designed mapping
      experiments. An alternative approach is in silico mapping, whereby genes are
      detected using existing phenotypic and genomic databases. We explored the
      usefulness of in silico mapping via a mixed-model approach in maize (Zea mays
      L.). Specifically, our objective was to determine if the procedure gave results
      that were repeatable across populations. Multilocation data were obtained from
      the 1995-2002 hybrid testing program of Limagrain Genetics in Europe. Nine
      heterotic patterns comprised 22,774 single crosses. These single crosses were
      made from 1,266 inbreds that had data for 96 simple sequence repeat (SSR)
      markers. By a mixed-model approach, we estimated the general combining ability
      effects associated with marker alleles in each heterotic pattern. The numbers of
      marker loci with significant effects--37 for plant height, 24 for smut [Ustilago
      maydis (DC.) Cda.] resistance, and 44 for grain moisture--were consistent with
      previous results from designed mapping experiments. Each trait had many loci with
      small effects and few loci with large effects. For smut resistance, a marker in
      bin 8.05 on chromosome 8 had a significant effect in seven (out of a maximum of
      18) instances. For this major QTL, the maximum effect of an allele substitution
      ranged from 5.4% to 41.9%, with an average of 22.0%. We conclude that in silico
      mapping via a mixed-model approach can detect associations that are repeatable
      across different populations. We speculate that in silico mapping will be more
      useful for gene discovery than for selection in plant breeding programs.

PMID- 15150692
TI  - Metastasectomy for renal cell carcinoma.

PMID- 15150691
TI  - A comparative study of the genetic bases of natural variation in tomato leaf,
      sepal, and petal morphology.
AB  - In an effort to better understand the dramatic differences in vegetative and
      floral morphology that differentiate species within the genus Lycopersicon,
      quantitative trait loci (QTL) for leaflet and perianth size and shape characters
      were mapped in an interspecific F2 population of tomato (Lycopersicon esculentum
      x L. pennellii). Thirty-six highly significant (P < or = 0.001) QTL were
      associated with 18 separate traits. QTL for correlated traits were generally not
      colocalized in the genome unless there was a clear codependence between the
      traits (e.g., organ length and area). Little or no overlap in QTL positioning
      between different organs was observed, suggesting that the genes determining the
      size and shape of leaflets, sepals, and petals are organ specific. Thus, while
      leaves are considered the developmental and evolutionary precursors to floral
      organs, genes acting late in development to determine certain aspects of
      morphology (namely shape and size) must have specialized to exert control over
      individual organs. Five of the leaflet-trait QTL map to analogous regions in the
      genome of eggplant, and therefore it appears there has been some conservation in
      the genes controlling leaf morphology within the Solanaceae.

PMID- 15150693
TI  - Human renal cell carcinoma inhibits dendritic cell maturation and functions.

PMID- 15150695
TI  - Heterozygosities and allelic frequencies of 811 dinucleotide-repeat marker loci
      in the Taiwanese population.
AB  - To evaluate basic informativeness of commercially available microsatellite
      markers in theTaiwanese population, 190 unrelated Taiwanese children were
      genotyped using ABI PRISM Linkage Mapping Set-HD5. The average heterozygosity in
      Taiwanese was slightly lower than that in Caucasians among these 811
      microsatellite markers. There were 50 marker loci with heterozygosities lower
      than 50%. Moreover, allelic distributions at many of the loci were significantly
      different in two ethnic groups. The results reported here represent a valuable
      database for disease genes mapping in the Taiwanese population. This database can
      be easily accessed at the Web site of Vita Genomics, Inc.
      (http://www.vitagenomics.com/str.html).

PMID- 15150694
TI  - [Prevention of bladder cancer].
AB  - Bladder cancer has a high incidence; therefore, the prevention of bladder cancer
      is useful. Each year 15,000 patients suffer from bladder cancer in Germany. These
      tumors are chemically induced and the development of bladder cancer is determined
      by the carcinogen and the time of exposure i.e., exposition time. Development of
      bladder cancer also depends on the patient's age. In patients younger than 45
      years bladder cancer is a rare disease. The incidence of bladder cancer is 3 of
      100,000 in males at the age of 45-50 years and it increases in the cohort of
      males older than 80 years to 200 of 100,000. Bladder cancer is a serious disease.
      The annual loss of life related to bladder cancer is 64,700 life years in Germany
      alone! Identification of carcinogens makes a preventative approach possible and
      leads to the detection of occupationally endangered people. Bladder cancer
      carcinogens include aromatic amines, medicaments (chlornaphazin, phenacetin, and
      cyclophosphamide), cigarette consumption, chronic infection of the lower urinary
      tract, radiation therapy of the pelvis, bilharciosis, Balkan nephropathy, and
      chronic interstitial nephritis.

PMID- 15150696
TI  - Identification of 45 novel SNPs in the 83-kb region containing peptidylarginine
      deiminase types 1 and 3 loci on chromosomal band 1p36.13.
AB  - Peptidylarginine deiminases (PADIs) are post-translational modification enzymes
      that catalyze the conversion of protein-bound arginine residues into citrulline
      residues in the presence of calcium ions. Among PADIs, PADI4 was identified as a
      rheumatoid arthritis-susceptibility gene (Suzuki et al. in Nat Genet 34:395,
      2003). We identified a total of 87 single nucleotide polymorphisms (SNPs) in
      PADI1 and PADI3 gene loci. Following a comparison of our data with SNPs in the
      dbSNP database in the National Center for Biotechnology Information, 45 SNPs are
      considered to be novel: 33 were identified in the PADI1 gene locus and 12 in the
      PADI3 gene locus. We also identified two insertion-deletion polymorphisms in
      introns of the PADI1. The high-resolution map that we constructed in this study
      will serve as a useful resource for analyzing gene scans of complex diseases
      mapped to this local segment on chromosomal band 1p36.13.

PMID- 15150699
TI  - Revealing gene transcription and translation initiation patterns in archaea,
      using an interactive clustering model.
AB  - An interactive clustering model based on positional weight matrices is described
      and results obtained using the model to analyze gene regulation patterns in
      archaea are presented. The 5' flanking sequences of ORFs identified in four
      archaea, Sulfolobus solfataricus, Pyrobaculum aerophilum, Halobacterium sp. NRC
      1, and Pyrococcus abyssi, were clustered using the model. Three regular patterns
      of clusters were identified for most ORFs. One showed genes with only a ribosome
      binding site; another showed genes with a transcriptional regulatory region
      located at a constant location with respect to the start codon. A third pattern
      combined the previous two. Both P. aerophilum and Halobacterium sp. NRC-1
      exhibited clusters of genes that lacked any regular pattern. Halobacterium sp.
      NRC-1 also presented regular features not seen in the other organisms. This group
      of archaea seems to use a combination of eubacterial and eukaryotic regulatory
      features as well as some unique to individual species. Our results suggest that
      interactive clustering may be used to examine the divergence of the gene
      regulatory machinery in archaea and to identify the presence of archaea-specific
      gene regulation patterns.

PMID- 15150700
TI  - Characterization of the trehalosyl dextrin-forming enzyme from the thermophilic
      archaeon Sulfolobus solfataricus ATCC 35092.
AB  - The trehalosyl dextrin-forming enzyme (TDFE) mainly catalyzes an intramolecular
      transglycosyl reaction to form trehalosyl dextrins from dextrins by converting
      the alpha-1,4-glucosidic linkage at the reducing end to an alpha-1,1-glucosidic
      linkage. In this study, the treY gene encoding TDFE was PCR cloned from the
      genomic DNA of Sulfolobus solfataricus ATCC 35092 to an expression vector with a
      T7 lac promoter and then expressed in Escherichia coli. The recombinant TDFE was
      purified sequentially by using heat treatment, ultrafiltration, and gel
      filtration. The obtained recombinant TDFE showed an apparent optimal pH of 5 and
      an optimal temperature of 75 degrees C. The enzyme was stable in a pH range of
      4.5-11, and the activity remained unchanged after a 2-h incubation at 80 degrees
      C. The transglycosylation activity of TDFE was higher when using maltoheptaose as
      substrate than maltooligosaccharides with a low degree of polymerization (DP).
      However, the hydrolysis activity of TDFE became stronger when low DP
      maltooligosaccharides, such as maltotriose, were used as substrate. The ratios of
      hydrolysis activity to transglycosylation activity were in the range of 0.2-14%
      and increased when the DP of substrate decreased. The recombinant TDFE was found
      to exhibit different substrate specificity, such as its preferred substrates for
      the transglycosylation reaction and the ratio of hydrolysis to transglycosylation
      of the enzyme reacting with maltotriose, when compared with other natural or
      recombinant TDFEs from Sulfolobus.

PMID- 15150701
TI  - Intervertebral mobility in the progressive degenerative process. A
      radiostereometric analysis.
AB  - Three separate stages have previously been defined in the progressive
      degenerative process. The first stage, characterized as temporary dysfunction
      with early degenerative findings, transforms into a second period of segmental
      instability evidenced by a resulting deformity. With the deformity the process
      has reached a late stage of definitive stabilization induced by osteoligamentary
      repair mechanisms. To test the validity of this three-stage hypothesis, we
      assessed the intervertebral mobility for the two most-distal lumbar disc levels
      in 18 adult patients with low back pain, disc degenerative findings and no prior
      spinal surgery. Each spinal segment was categorized according to grade of disc
      degeneration: (IA) normal disc height without dehydration; (IB) normal disc
      height with dehydration; (II) disc height decreased by less than 50%; (III) disc
      height decreased by at least 50%; and (IV) disc height obliterated. The
      intervertebral mobility was measured by radiostereometric analysis (RSA) and
      compared between the categories. With the patient changing position from supine
      to sitting, the mean vertical translation across the 11 discs categorized as IA
      was 2.0 mm. A small increase in mean vertical mobility with progressive loss of
      disc height through the degenerative stages IB (2.2 mm, seven discs) and II (2.6
      mm, ten discs) was not significant. Further degeneration to grade III meant a
      significant mean reduction in vertical mobility to 0.8 mm for the eight discs in
      that category. No discs were classified as obliterated, category IV. The
      corresponding values for sagittal translations were 3.0 mm, 3.1 mm, 3.6 mm and
      1.7 mm for the four disc categories found. These alterations were not
      statistically significant. We conclude that intervertebral mobility changes
      throughout the degenerative process, and a stage of stabilization begins when
      disc height is reduced by 50%. The segmental mobility status cannot be deduced
      from the radiographic, degenerative disc stage, since the inter-individual
      differences in mobility are pronounced for the same disc status. A fully stable
      situation cannot be taken for granted, even when the disc is reduced by more than
      50%, considering the fact that some persisting mobility was seen for most
      patients in category III. A preceding stage of instability, in the clinical
      situation proven by a resulting deformity, was not verified in this study.

PMID- 15150702
TI  - Validation of the Tunisian version of the Roland-Morris questionnaire.
AB  - Our aim was to validate a culturally adapted, Tunisian-language version of the
      Roland-Morris Disability Questionnaire (RMDQ), which is a reliable evaluation
      instrument for low-back-pain disability. A total of 62 patients with low back
      pain were assessed by the questionnaire. Reliability for the 1-week test/re-test
      was assessed by a construction of a Bland Altman plot. Internal construct
      validity was assessed by Cronbach's alphatest. External construct validity was
      assessed by association with pain, the Schober test and the General Function
      Score. Sensitivity to change was determined using a t-test for paired data to
      compare RMDQ scores at inclusion and at completion of the therapeutic sequence of
      local corticosteroid injections. We also compared the questionnaire score with
      the General Function Score, both taken after completion of the therapeutic
      sequence. The constructed Bland Altman plot showed good reliability. Internal
      consistency of the RMDQ was found to be very good and the Cronbach's alpha test
      was 0.94, indicating a good internal construct validity. The questionnaire is
      correlated with the pain visual analogue scale (r=33; p=0.0001), with the Schober
      test (r=0.27; p=0.0001) and the General Function Score (r=56; p=0.0001)
      indicating an adequate external construct validity. The RMDQ administered after
      the therapeutic sequence is sensitive to change (r=0.83; p=0.000). Comparison of
      the questionnaire score to the General Function Score, after completion of the
      therapeutic sequence, was satisfactory (r=0.75; p=0.000). We conclude that the
      Tunisian version of the Roland-Morris questionnaire has good reliability and
      internal consistency. Furthermore, it has a good internal- and external construct
      validity and high sensitivity to change. It is an adequate and useful tool for
      assessing low-back-pain disability.

PMID- 15150703
TI  - The costs for persons sick-listed more than one month because of low back or neck
      problems. A two-year prospective study of Swedish patients.
AB  - The total costs for patients who are sick-listed due to back and neck problems
      have not previously been determined prospectively on an individual basis. This
      study aimed to determine the total cost to a society, based on individually
      assessed costs of health services and loss of production in people who are sick
      listed 28 days or more for back or neck problems. Detailed data on individuals'
      health-care consumption due to back or neck problems was collected through
      prospectively entered diaries and questionnaires, after 4 weeks, 3 months, 1 and
      2 years, in a consecutively selected cohort of 1,822 employed persons aged
      between 18 and 59 years. Costs for health care and production losses due to work
      absenteeism were determined individually and combined to render total costs to
      society. The costs for all medical services during the 2-year study were 6.9% of
      total costs for back and neck problems. The single most expensive medical service
      was surgery. Transferred to a national level, annual total costs for back and
      neck problems corresponded to 1% of GNP. In conclusion, direct health-service
      costs were a small fraction of the total costs, consequently indirect costs offer
      the greatest potential for savings.

PMID- 15150705
TI  - [Oculopharyngeal muscular dystrophy: from the paradigm of the dynamic mutations
      to toxic proteinopathies].

PMID- 15150704
TI  - Patient perceptions about chemotherapy-induced oral mucositis: implications for
      primary/secondary prophylaxis strategies.
AB  - GOALS: Oral mucositis (OM), the painful inflammation of oropharyngeal tissues, is
      an economically costly chemotherapy toxicity. Several agents to prevent
      chemotherapy-induced OM are in development, with most studies conducted among
      transplantation subjects with a brief well-defined risk period. The potential
      value of these preventative agents among hematology-oncology populations
      receiving cyclic standard-dose therapy is unknown. PATIENTS AND METHODS: Patients
      receiving standard-dose chemotherapy at an outpatient oncology center over a 2
      week time-frame were invited to participate in an anonymous unprompted survey.
      The survey instrument consisted of six demographic questions and six questions
      regarding toxicities of chemotherapy. RESULTS: Of 514 patients providing
      completed surveys from among approximately 1625 patients (32% response rate), 167
      (32%) reported experiencing OM. Factors associated with developing OM included
      number of chemotherapy cycles ( P=0.001), hematologic malignancy ( P=0.02),
      female gender ( P=0.03), age ( P=0.05), and treatment with anthracyclines (
      P=0.001), vinca alkaloids ( P=0.001), cyclophosphamide ( P=0.001), fludarabine (
      P=0.01), cis/carboplatin ( P=0.05) and radiotherapy ( P=0.005). Among patients
      experiencing OM, 69% considered OM to be an important toxicity with 7% rating
      their OM very severe, 18% severe, 36% moderate and 29% mild. Recurrent OM was
      reported by 87 patients (53%) and was judged similar in severity by 67%, milder
      by 27% and more severe by 6%. OM was considered the sixth most distressing
      complication behind (in descending order) fatigue, hair loss, nausea, numbness
      and diarrhea, and more important than anxiety and heartburn. CONCLUSIONS: OM
      represents a common toxicity of standard-dose chemotherapy occurring in
      approximately one-third of patients. High-risk populations can be identified,
      permitting targeting of primary prophylaxis strategies whereby all patients
      possessing high-risk factors are treated to prevent OM. However, since OM was
      self-reported by only one-third of patients receiving standard-dose chemotherapy,
      but over half of those experiencing OM developed recurrent episodes, secondary
      prophylaxis strategies targeting recurrent OM episodes may be more appropriate.

PMID- 15150707
TI  - [Preliminary normative data for the second edition of the Boston Naming Test for
      young Spanish adults].
AB  - INTRODUCTION: The Boston Naming Test (BNT) is one of the most widely used tests
      in neuropsychological evaluation of language disorders, specifically when testing
      for anomia. The aim of this study is to establish preliminary normative data for
      the second edition of the BNT for young spanish adults (age range between 20 and
      49 years). METHODS: A total of 160 subjects (60 % female and 40 % male) were
      administered the BNT. Mean age was 33.89 years (SD: 9.45) and average number of
      years of education was 13.98 (SD: 3.97). The version used in the present study is
      the second edition of the BNT (Kaplan et al., 2001) which includes two new
      components: multiple choice and error typology. STATISTICAL ANALYSIS: Descriptive
      statistics of the test's variables. Lineal regression to establish the possible
      degree of influence of the variables age and education on test performance.
      RESULTS: The sample's mean score was 51.84. Education significantly influences
      the final score (B: 0.476; p= 0.001). Multiple choice was effective in 89 % of
      cases. DISCUSSION: The present results will allow proper clinical interpretation
      of results in the BNT 2001 version in young Spanish adults.

PMID- 15150706
TI  - [Oculopharyngeal muscular dystrophy: study of patients from seven Spanish
      families with different GCG expansions in PABP2 gene].
AB  - INTRODUCTION: Autosomal dominant oculopharyngeal muscular dystrophy (OPMD), with
      late onset due to ptosis and/or dysphagia, is caused by short (GCG)8-13 triplet
      repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is
      localized in chromosome 14q11. The severity of the dominant OPMD as well as the
      number of expansions that cause the disease are variable. (GCG)9 is mentioned as
      the most frequent and the genotype/phenotype has still not been well-determined.
      OBJECTIVE: To describe the type of expansions (GCG)n found in Spanish families
      with OPMD, establishing if there is variability of them and the possible geno
      phenotypical correlations. METHODS: Clinicopathological and molecular studies
      have been performed in 15 consecutive patients, belonging to seven Spanish
      families with OPMD. The muscular biopsy study under electronmicroscopy shows
      intranuclear inclusions (INIs) in all the examined patients (one patient per
      family). The genetic findings confirm the cause of the disease in all the
      affected members and in one clinically asymptomatic member of one recently
      examined family: three families (six, one and one studied members, respectively)
      present the (GCG)9 expansion, two families (one studied member each one) present
      the (GCG)10 expansion and two families (one and four studied members
      respectively) present the (GCG)11 expansion. In these 15 patients with a short
      GCG expansion causing OPMD, clinical tests for OPMD and a follow-up study of
      their clinical course have been carefully assessed: in patients with the (GCG)9
      expansion major abnormalities appeared in extrinsic ocular mobility and more
      precocious presentation of limb girld (lumbopelvic preferentially) weakness
      leading to a great disability before the seventh decade of life under the
      seventies in some patients and sometimes leading to death. In patients with
      (GCG)10 and (GCG)11 expansions, eye movements are always preserved and the limb
      girld muscles weakness did not appear before the seventh decade. No correlation
      seems to exist between age of onset of the ptosis or dysphagia and the different
      (GCG)n expansions and the surgical treatment of ptosis, performed in eight
      patients, showed good results independently of the (GCG)n mutation. CONCLUSIONS:
      Although further clinical and genetic studies are necessary to establish a strict
      genotype/phenotype correlation in OPMD, we concluded that the (GCG)9 expansion
      involve more severe phenotypes than those related to the (GCG)10 or (GCG)11
      expansions. Therefore, genetic testing could benefit prognosis in asymptomatic
      individuals.

PMID- 15150708
TI  - [Intracranial stenosis. Study and follow-up of 38 patients].
AB  - INTRODUCTION: To describe vascular risk factors of patients harboring
      intracranial arterial stenosis (IAS) as well their final outcome. METHODS: We
      reviewed clinical reports of all patients admitted to our Institution from April
      1, 1999 to November 30, 2001 with the diagnosis of IAS. Diagnosis was made by
      means of magnetic resonance angiography (MRA) or four-vessels digital subtraction
      angiography. Thirty-eight patients harboring 56 IAS were identified. Mean follow
      up was 18 months. Two control groups were selected: one was a group of 44
      patients with stroke and embolic cardiopathy (EC) and the other was a group of 67
      patients with stroke and extracranial stenosis without IAS. RESULTS: Mean age was
      69.7 years, with male preponderance (76.3 %). Seventeen cases (44.7 %) had
      associated extracranial carotid stenosis greater than 50 %. Multiple IAS were
      found in 12 patients. Diabetes mellitus was significantly more frequent in the
      IAS group than in both control groups. On the other hand, cigarette smoking was
      more common in the IAS group with respect to the EC group. IAS was symptomatic in
      25 cases, whereas in 13 patients IAS was found in the work-up for cerebral
      ischemia in another territory. From the group of symptomatic patients, 22 (88 %)
      had a Rankin scale 2 or lower on discharge and, in the long term follow-up, their
      incidence rate of recurrent ischemic stroke was 15 per 100 patients/year.
      CONCLUSIONS: Diabetes mellitus was the most specific risk factor for IAS. IAS was
      multiple in 32% of patients and in extracranial stenosis from moderate to severe
      degree was found in 44.7% of the cases. Stroke secondary to IAS caused a low
      dependency level at discharge. Incidence rate of recurrent ischemic stroke was 15
      % patients/ year.

PMID- 15150709
TI  - [Influence of botulinum toxin treatment on previous primary headaches in patients
      with cranio-cervical dystonia].
AB  - INTRODUCTION: Preliminary data suggest some beneficial effects of botulinum toxin
      type A (BT-A) on primary headaches. OBJECTIVE: To analyze the subjective
      influence of BT-A on previous primary headaches of those patients receiving this
      treatment due to a variety of cranio-cervical dystonia (CD). PATIENTS AND
      METHODS: All patients receiving BT-A due to CD were interviewed with an ad hoc
      questionnaire on the presence or not of headaches prior to BT treatment.
      Diagnosis and subjective effects of BT-A on these previous headaches were
      recorded. RESULTS: Thirty-eight patients (28 women) were interviewed; 21 (19
      women) reported a history of previous primary headache (12 migraine, 10 tension
      type headache). Nine (41 %) reported sustained response ( > 50 % reduction in
      headache frequency) since the beginning of BT-A treatment. Patients with cervical
      dystonia or those receiving high doses ( > 50 U) showed the best responses. Age,
      gender, pain location, duration of BT-A treatment and headache diagnosis did not
      seem to correlate with response. CONCLUSIONS: BT-A seems to have sustained
      beneficial effect on primary headaches of some patients with CD, especially at
      doses higher than 50 U and in patients with the diagnosis of spasmodic
      torticollis.

PMID- 15150710
TI  - [Different phenotypes of Charcot-Marie-Tooth disease caused by mutations in the
      same gene. Are classical criteria for classification still valid?].
AB  - Molecular genetic research is leading to the continuous discovery of new genes
      and protein involved in peripheral nerves function. Simultaneously, extended
      clinical, neurophysiological and pathological research has yielded new genotype
      phenotype correlation on Charcot-Marie-Tooth disease (CMT). This has made it
      possible to know that several genes can cause both demyelinating (CMT1) and
      axonal (CMT2) phenotypes. Those observations have questioned the validity of some
      current criteria for CMT classification and raise the need for new strategies for
      diagnosis. The discovery of Schwann cell-axon interaction is a challenge for
      coming years. In this review, we extensively analyzed mutations of genes that
      give rise to CMT1 or CMT2 phenotypes. There are at least three forms of genetic
      variability. MPZ gene mutations yield a real allelism, that is, CMT1 or CMT
      phenotypes associated to specific mutation by site or quality. GADP1 and probably
      NF-L gene manifest different phenotypes but only in terms of nerve conduction
      velocity (CV). Evidence is provided that indicates that CV reduction in GADP-1
      neuropathy may be the result of axonal loss. Finally a third form of variability
      is present in CMTX due to the degree of clinical expression in females related
      with the inactivation of chromosome X.

PMID- 15150711
TI  - [Obnubilation and vertical gaze paralysis secondary to bilateral thalamic
      infarction].

PMID- 15150713
TI  - Hemorrhagic unilateral moyamoya: report of one case.
AB  - A 29 year old woman presented with an intracerebral hemorrhage. Angiographic
      findings were consistent with unilateral moyamoya. The patient was managed non
      surgically and discharged with the indication of periodical followup angiography.
      Moyamoya is a rare entity that must be considered in the differential diagnosis
      of ischemic or hemorrhagic cerebrovascular events. At present, the natural
      history of unilateral moyamoya is not well established in relation to the
      progression to a bilateral form and to rebleeding risk. Periodical follow-up
      angiography (conventional or MRI) seems a reasonable management strategy.

PMID- 15150712
TI  - [Intracerebral haemorrhage by cerebral hyperperfusion after carotid angioplasty
      in a tandem lesion. A case report].
AB  - Intracerebral hemorrhage (ICH) by hyperperfusion after carotid angioplasty has a
      frequency of 1.2 % - 4.4% in the literature. Until now no case of ICH after
      carotid angioplasty in a tandem lesion has been reported. We present the case of
      a patient who suffered an ICH due to the hyperperfusion syndrome, after carotid
      angioplasty of two stenotic lesions of the left internal carotid artery (ICA)
      (intracranial and extracranial). He was a 58 year old man who suffered repetitive
      left carotid TIA despite being treated with antiplatelet therapy. An angiogram
      showed 76 % extracranial stenosis and 96 % intracranial stenosis of the left ICA
      as well as 59 % extracranial stenosis of right ICA. Angioplasty with stenting of
      the two stenosis of the left ICA was performed. After 48 hours of the
      angioplasty, the patient presented a massive ICH and died a few hours later. ICH
      by hyperperfusion is an infrequent complication of the carotid angioplasty. The
      risk factors of the ICH should be evaluated in order to decrease their incidence
      as well as to maintain an intensive control of the arterial pressure during and
      after the procedure. This case is the first one published after angioplasty of a
      tandem lesion. It is possible that the pathophysiologic mechanism involved was an
      excessively rapid restitution of the normal arterial size.

PMID- 15150714
TI  - [Cervical myelopathy secondary to traumatism in patient with posterior vertebral
      ligament calcification].

PMID- 15150715
TI  - Sensitivity to changes in disability after stroke: a comparison of four scales
      useful in clinical trials.
AB  - Although most current stroke intervention trials use disability scales to
      determine outcome, little is known about the sensitivity to change of these
      scales. The use of a more sensitive measure would increase the statistical power
      of rehabilitation treatment trials. We applied four well-known disability scales
      to a group of stroke rehabilitation inpatients to compare sensitivity to change.
      Ninety-five consecutive admissions to a stroke rehabilitation service were
      assessed for disability on admission and discharge. Two global scales, the
      Modified Rankin Scale (MRS) and the International Stroke Trial Measure (ISTM),
      were compared with two activities of daily living (ADL) scales, the Barthel Index
      (BI) and the Functional Independence Measure (FIM). We determined the number of
      patients that each scale detected a clinically significant change in disability.
      Standardized response means (SRM) and receiver operating characteristic (ROC)
      analyses were performed. The MRS detected change in 55 subjects, including all
      who changed on the ISTM; the ISTM detected change in only 23 subjects. The BI
      detected change in 71 subjects but demonstrated ceiling effects with 26% of
      subjects scoring >95. The FIM was most sensitive, detecting change in 91
      subjects; no patient achieved a maximum score. The SRM of the FIM was superior to
      that of the BI (2.18 versus 1.72), and ROC analysis revealed C-statistics of 0.82
      for the BI, 0.59 for the MRS, and 0.51 for the ISTM. Global scales were much less
      sensitive to changes in disability than were ADL scales. Though ADL scales may
      take longer to administer, their increased sensitivity may make them more useful
      in treatment trials by allowing fewer subjects to be enrolled.

PMID- 15150716
TI  - Transverse rotation and longitudinal translation during prosthetic gait--a
      literature review.
AB  - Improved technology allows for more accurate gait analysis to increase awareness
      of nonoptimized prosthetic gait patterns and for the manufacture of sophisticated
      prosthetic components to improve nonoptimized gait patterns. However,
      prescriptions are often based on intuition rather than rigorous research findings
      for evidence-based practice. The number of studies found in the literature that
      are based on prosthetic research regarding transverse rotation and longitudinal
      translation is small when compared to topics regarding other types of movements.
      Some design criteria for prosthetic components described in those studies that
      permit transverse rotation and longitudinal translation can be found in current
      designs. However, little research has been conducted to establish their
      effectiveness on the gait parameters and residual limb. This literature review is
      an investigation into these motions between the socket and the prosthetic foot,
      with particular reference to gait characteristics and prosthetic design criteria.

PMID- 15150717
TI  - Reliability of measures of gait performance and oxygen consumption with stroke
      survivors.
AB  - This study assessed the reliability of gait performance with concurrent measures
      of oxygen consumption (VO2) in stroke survivors (SS). Nine male SS (60.00 +/-
      15.08 yr) had a recent history of stroke (44.56 +/- 51.35 days since the stroke)
      and were receiving rehabilitation. Four had a right cerebrovascular accident
      (CVA), and five had a left CVA. Subjects walked without assistance, although
      three used a single cane to complete the test. Within 30 minutes, subjects
      completed two trials of a 5 min walk while walking back and forth on a 5 m
      walkway wearing a portable gas analyzer to collect samples of gases. The
      intraclass correlation coefficient (ICC) was used to assess reliability. The ICC
      for gait energy expenditure, walk distance, gait speed, and gait energy cost were
      0.64, 0.97, 0.95, and 0.97, respectively. Assessment of gait performance with
      concurrent measures of VO2 is a reliable procedure with SS.

PMID- 15150718
TI  - Upper-limb fatigue-related joint power shifts in experienced wheelchair users and
      nonwheelchair users.
AB  - This paper evaluates power transfer or shifting across upper-limb segments,
      resulting from fatigue-inducing wheelchair propulsion. Nineteen manual wheelchair
      users (WCUs) and ten nonwheelchair users (NUs) participated in this study.
      Subjects propelled an instrumented wheelchair ergometer at a workload
      corresponding to 75% of the peak oxygen uptake attained during a maximal-graded
      exercise tolerance test. Subjects were required to propel the wheelchair for as
      long as they could at a constant velocity of 3 km/h (32 rpm). The test was
      terminated when subjects could no longer maintain the target velocity. Peak
      Performance video-capture system was used to determine upper-limb kinematics.
      Handrim forces and joint kinematics were used to calculate joint moments and
      power with the use of an inverse dynamics approach. Results showed that with
      fatigue, joint power shifts from the shoulder joint to the elbow and wrist
      joints. Implications for joint injury and propulsion efficiency are discussed.

PMID- 15150719
TI  - Kinematic and dynamic performance of prosthetic knee joint using six-bar
      mechanism.
AB  - Six-bar linkages have been used in some prosthetic knees in the past years, but
      only a few publications have been written on the special functions of the
      mechanism as used in transfemoral prosthesis. This paper investigates the
      advantages of the mechanism as used in the prosthetic knee from the kinematic and
      dynamic points of view. Computer simulation and an experimental method were used
      in the investigation. The results show that the six-bar mechanism, as compared to
      the four-bar mechanism, can be designed to better achieve the expected trajectory
      of the ankle joint in swing phase. Moreover, a six-bar linkage can be designed to
      have more instant inactive joints than a four-bar linkage, hence making the
      prosthetic knee more stable in the standing phase. In the dynamic analysis, the
      location of the moment controller was determined for minimum value of the control
      moment. A testing prosthetic knee mechanism with optimum designed parameters was
      manufactured for experiments in the laboratory. The experimental results have
      verified the advantage revealed in the analyses.

PMID- 15150720
TI  - Psychosocial effects of an exercise program in older persons who fall.
AB  - Falling is associated with psychosocial sequelae that may influence functional
      performance and fall risk. Exercise can improve psychosocial factors. To address
      the research questions (1) Do psychosocial variables differ among persons with
      and without falls? and (2) Among persons who fall, can exercise improve
      psychosocial variables? we evaluated psychosocial and functional performance
      variables in older persons with and without recent falls. A pretest and posttest
      design with a nonequivalent control group was used. Community-residing elderly
      individuals participated, 66 had falls in the past year (fallers) and 77 had no
      falls (nonfallers). Participants completed measures of self-esteem, depression,
      psychological impact, and functional performance at baseline and 6 weeks.
      Baseline descriptive characteristics for fallers and nonfallers were similar.
      Fallers then completed a 6-week exercise program. Exercise benefited fallers'
      self-esteem, depression, mobility, social role, social activity, and anxiety.
      Nearly 40% of fallers were clinically depressed before exercise and 24% were
      depressed after (p = 0.04). Psychosocial variables correlated significantly with
      quality of functional performance (p < 0.019). Among fallers, moderate exercise
      produced a significant improvement in psychosocial variables and functional
      performance (p < 0.045).

PMID- 15150721
TI  - Psychological correlates of illusory body experiences.
AB  - Postamputation phantom sensations and phantom pain, i.e., sensation or pain in
      the amputated limb, can be extremely distressing for people who have had
      amputations. Recent research on treating phantom phenomena has used the
      experimental induction of illusory body experiences. Although the suggestion has
      been that such experiences may influence the cortical remapping that occurs after
      amputation, the role of psychological factors in these experimental inductions
      has not been addressed. We used an able-bodied sample to investigate whether a
      common underlying propensity exists for illusory body experiences and whether the
      occurrence of these experiences is associated with previously neglected
      psychological variables. Psychometric measures of body plasticity, somatic
      preoccupation, and creative imagination were significantly and differentially
      associated with the occurrence of illusory body experiences. Hence, these
      measures have potential use in identifying patients most likely to benefit from
      treatment interventions using the induction of illusory body experiences.

PMID- 15150724
TI  - Evidence-based rehabilitation: the case for and against constraint-induced
      movement therapy.

PMID- 15150722
TI  - Experimental study of decubitus ulcer formation in the rabbit ear lobe.
AB  - An animal model of decubitus ulcer was created with the use of ear lobes of
      Japanese white rabbits. When the strength of the cyclic compressions and the
      duration of the cycles of compression and release are adjusted, the model
      successfully reproduced the four grades used to characterize decubitus ulcer.
      Compressions were recorded with video microscopy to continuously monitor the
      changes in tissue blood flow, in both the compressed and surrounding regions.
      This model is unique insofar as the blood-flow characteristics are clearly
      visible before, during, and after compression. Because long-term observation is
      possible in a living-body model, our study can easily be extended.

PMID- 15150725
TI  - Prior experience, antioxidants, and mitochondrial cofactors improve cognitive
      function in aged beagles.
AB  - Results of this study support the free-radical theory of aging and demonstrated
      that providing higher levels of vitamin E in food resulted in higher serum
      vitamin E concentrations and improved performance on landmark-discrimination
      tasks in aged dogs. Factors other than vitamin E also contributed to the response
      but remain undefined.

PMID- 15150726
TI  - Rapid onset of protection against infectious bovine rhinotracheitis with a
      modified-live virus multivalent vaccine.
AB  - This study provides evidence that subcutaneous vaccination of cattle with a
      commercially available modified-live virus combination vaccine can help reduce
      clinical signs associated with infectious bovine rhinotracheitis infections in
      feedlot animals vaccinated at the time of arrival. Calves vaccinated 72 or 96
      hours before challenge had reduced clinical signs, lower body temperatures, lower
      virus titers, and 39% to 76% greater weight gains compared with nonvaccinated
      controls.

PMID- 15150727
TI  - Evaluation of porfimer sodium in dogs and cats with spontaneous tumors.
AB  - The effect of photodynamic therapy is a function of several variables, including
      selective retention of the drug in tumor tissue with reduced drug concentration
      in surrounding normal tissue. A study was designed to determine the
      pharmacokinetic profile and variability of porfimer sodium in dogs and cats with
      spontaneous tumors and to thereby determine the optimal timing of its
      photoactivation in these species. The results of this study indicate that there
      is marked variability among species in the distribution of porfimer sodium
      between highly proliferating tissues, which requires careful attention in the
      design of human and veterinary application of photodynamic therapy with porfimer
      sodium, as determined in rodent models.

PMID- 15150728
TI  - Evaluation of immune responses in horses immunized using a killed Sarcocystis
      neurona vaccine.
AB  - Clinically normal horses developed cellular immunity to Sarcocystis neurona
      following IM vaccination with a commercial killed S. neurona vaccine, as
      indicated by the development of measurable anti-S. neurona IgG antibodies and
      additional intradermal skin testing. Large-scale independent assessments of the
      vaccine's performance and safety are in progress under field conditions. The next
      step in the evaluation of this vaccine would be to attempt experimental challenge
      after a reproducible reliable equine model of S. neurona encephalitis has been
      established that allows for reisolation of the pathogen after challenge.

PMID- 15150729
TI  - Evaluation of two diets in the nutritional management of cats with naturally
      occurring chronic diarrhea.
AB  - Feeding either a highly digestible, moderate-carbohydrate diet or a highly
      digestible, high-protein, low-carbohydrate diet resulted in significant (P < .05)
      improvements in fecal scores in 71% of cats with chronic, nonspecific diarrhea.
      Approximately 58% of the cats improved on either diet, with no significant
      differences between the two diets regarding the percentage of cats responding or
      the degree of response. These results suggest that dietary management may be
      helpful in cats with chronic diarrhea. If cats do not respond within 1 month, an
      alternative diet should be considered.

PMID- 15150730
TI  - Biochemical and metabolic changes due to exercise in sprint-racing sled dogs:
      implications for postexercise carbohydrate supplements and hydration management.
AB  - Evaluations of biochemical changes associated with spring-style sled dog racing
      indicate that differences in cortisol, lactate, and serum glucose levels suggest
      exercise of moderate duration (but high intensity) has metabolic demands that dif
      fer from those for typical endurance sled dog racing. Additionally, hematocrit,
      albumin, sodium, chloride, and blood urea nitrogen levels decreased in one team
      of dogs, whereas there were mild increases in sodium, chloride, and blood urea
      nitrogen in the other team. These opposing biochemical findings suggest
      physiologic changes associated with differences in hydration status, likely
      attributed to different dietary and hydration strategies used by the respective
      kennels.

PMID- 15150731
TI  - Pharmacokinetics and lung tissue concentrations of tulathromycin, a new
      triamilide antibiotic, in cattle.
AB  - The pharmacokinetics of the new triamilide antibiotic tulathromycin was
      investigated in two cattle studies. Following a single subcutaneous injection,
      the drug was rapidly absorbed and bioavailability was excellent. High and
      persistent levels of the drug in lung tissue were observed as well. These
      attributes are advantageous for an antimicrobial drug indicated for the treatment
      of bacterial and mycoplasmal respiratory diseases in cattle.

PMID- 15150733
TI  - Feeding practices of pet dogs and determination of an allometric feeding
      equation.
AB  - This study indicates that measuring caloric intake data of dogs in homes is
      achievable and can provide a practical and appropriate methodology for
      determining energy needs. This knowledge can be helpful in developing appropriate
      guidelines for pet food labels.

PMID- 15150732
TI  - Human recombinant interferonalpha-2b for management of idiopathic recurrent
      superficial pyoderma in dogs: a pilot study.
AB  - The oral use of human recombinant interferonalpha-2b at 1,000 IU/ml/day appeared
      to provide only a transient benefit as compared with placebo for management of
      idiopathic recurrent superficial pyoderma in dogs. Further investigation using a
      larger population of dogs is needed to determine whether interferon is effective
      for long-term treatment of this condition.

PMID- 15150734
TI  - Diet and chronic haloperidol effects on rat midbrain dopamine neurons.
AB  - The effects of dietary glucose (chow containing 0%, 10%, 20%, or 40% glucose,
      w/w) on chronic haloperidol-induced changes in dopamine (DA) neuronal activity
      were tested. Rats were treated daily by oral gavage for 21 days with either water
      or 0.5 mg/kg haloperidol, then anesthetized for in vivo electrophysiological
      recording. The numbers of spontaneously active DA neurons in the substantia nigra
      (A9) and ventral tegmental area (A10) regions of the midbrain were estimated with
      the cells-per-track sampling method. In rats fed standard chow, haloperidol
      significantly reduced the number of active neurons in both regions compared to
      water controls. In water controls there were no differences in DA cells per track
      between rats fed standard chow or chow containing 10% or 20% glucose, whereas
      these glucose diets significantly attenuated the effects of chronic haloperidol
      on DA cells per track. The 40% glucose diet itself nonsignificantly reduced cells
      per track and, in turn, nonsignificantly attenuated the effects of haloperidol.
      The results demonstrate that dietary glucose content can alter haloperidol
      induced changes in the activity of midbrain DA neurons.

PMID- 15150735
TI  - Distinct expression and distribution of vesicular proteins in the hippocampus of
      TNFa-deficient mice during development.
AB  - Tumor necrosis factor alpha (TNFa) is a cytokine produced mainly by cells of the
      immune system. It is also expressed by brain neurons and glia. In the brain, TNFa
      governs synaptic plasticity, such as long-term potentiation and learning. Using
      TNFa-deficient mice (TNFa-KO) and immunohistochemical techniques, we resolved the
      spatio-temporal effect of TNFa on the expression of vesicular soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (v-SNARE) in the
      presynaptic terminals of the hippocampus during the first month of development.
      During postnatal days 1-14, the levels of Synaptotagmin I and VAMP II were
      similar in the hippocampus of TNFa-KO and wild type (wt) mice. However, the
      levels of Syntaptotagmin II were reduced in the pyramidal cell layer of the CA1
      region in TNFa-KO. At postnatal day 21, both proteins accomplished comparable
      levels in the hippocampus of TNFa-KO and wt mice. In addition, TNFa deficiency
      impairs the correlation of expression of Synaptotagmin I and II in CA1 region.
      The expression of those proteins in the CA1 stratum radiatum was uniform during
      development and similar in both mice groups. Higher expression of all examined
      proteins was demonstrated in dendritic fields of the CA3 region in TNFa-KO as
      compared to wt mice. We suggest that the impairment of synaptic plasticity by
      TNFa may be related to its modulation of synaptic vesicle proteins.

PMID- 15150736
TI  - Effect of early life stress on serotonin responses in the hippocampus of young
      adult rats.
AB  - In this study, we investigated the effects of early life stress on several
      aspects of serotonin (5-HT) transmission in hippocampus, later on in life. Three
      day-old rats were subjected to 24-hour maternal deprivation or control treatment.
      Maternal deprivation is known to activate the hypothalamo-pituitary-adrenal axis,
      resulting in increased corticosterone levels at a time-point in life when the
      axis is particularly insensitive to most stressful stimuli. When these animals
      had matured to 3 months of age, functional responses to 5-HT as well as 5-HT1A
      receptor mRNA expression were examined. Also, indices for hypothalamo-pituitary
      adrenal function were studied in the adult state, including hippocampal mRNA
      expression for the mineralocorticoid and the glucocorticoid receptor. Resting
      membrane potential of CA1 pyramidal neurons was significantly depolarized in
      animals earlier subjected to maternal deprivation compared to the controls.
      Despite this depolarized resting potential, hyperpolarizing responses induced by
      5-HT in CA1 pyramidal neurons from deprived compared to non-deprived rats were
      attenuated. This attenuation in 5-HT response was not accompanied by changes in
      mRNA expression of the 5-HT1A-receptor. Maternal deprivation was not found to
      change any of the neuroendocrine parameters investigated once animals had
      matured. We conclude that maternal deprivation can alter specific aspects of
      hippocampal 5-HT transmission later on in life, possibly by post-translational
      modification of the 5-HT1A-receptor or changes in the 5-HT1A-receptor signal
      transduction pathway.

PMID- 15150737
TI  - Sexual experience alters D1 receptor-mediated cyclic AMP production in the
      nucleus accumbens of female Syrian hamsters.
AB  - Drugs of abuse produce long-term changes in dopamine neurotransmission and
      receptor-effected intracellular signaling. Similar changes in neuronal activity
      are mediated by motivated behaviors. To explore cellular mechanisms underlying
      these neuroadaptations following sexual experience, cyclic AMP accumulation
      following stimulation of D1 dopamine receptors, G-proteins, and adenylate cyclase
      was compared in the nucleus accumbens and caudate nucleus of sexually naive and
      experienced female hamsters following sexual behavior. Direct stimulation of
      adenylate cyclase with forskolin or indirectly by activation of G-proteins with
      Gpp(NH)p produced dose-dependent increases in the formation of cyclic AMP in the
      nucleus accumbens and caudate nucleus, with no effects of sexual experience on
      these measures. Specific D1 receptor stimulation increased Gpp(NH)p-induced
      adenylate cyclase activity in the nucleus accumbens and caudate nucleus of all
      animals. Interestingly, this stimulation was further enhanced only in membranes
      from the nucleus accumbens, but not from the caudate nucleus, of sexually
      experienced hamsters compared to the response of naive females. These results
      demonstrate that sexual behavior experience can sensitize mesolimbic dopamine
      pathways and that this sensitization occurs through an increase in D1 receptor
      mediated signaling.

PMID- 15150738
TI  - NMDA receptor blockade attenuates locomotion elicited by intrastriatal dopamine
      D1-receptor stimulation.
AB  - Previous behavioral studies suggest that the striatum mediates a hyperactive
      response to systemic NMDA receptor antagonism in combination with systemic D1
      receptor stimulation. However, many experiments conducted at the cellular level
      suggest that inhibition of NMDA receptors should block D1 receptor-mediated
      locomotor activity. Therefore, we investigated the consequences of NMDA receptor
      blockade on the ability of striatal D1 receptors to elicit locomotor activity
      using systemic and intrastriatal injections of the NMDA antagonist MK-801
      combined with intrastriatal injections of the D1 full agonist SKF 82958.
      Following drug treatment locomotor activity was measured via computerized
      activity monitors designed to quantify multiple parameters of rodent open-field
      behavior. Both systemic (0.1 mg/kg) and intrastriatal (1.0 microg) MK-801
      pretreatments completely blocked locomotor and stereotypic activity elicited by
      10 microg of SKF 82958 directly infused into the striatum. Further, increased
      activity triggered by intrastriatal SKF 82958 was attenuated by a posttreatment
      with intrastriatal infusion of 1 microg MK-801. These data suggest that D1
      stimulated locomotor behaviors controlled by the striatum require functional NMDA
      channels.

PMID- 15150739
TI  - Development of vigabatrin-induced lesions in the rat brain studied by magnetic
      resonance imaging, histology, and immunocytochemistry.
AB  - Vigabatrin, the gamma-aminobutyric acid transaminase (GABA-T)-inhibiting
      anticonvulsant drug, was given orally at a dose of 275 mg/kg/day to rats (n = 6)
      in their feed for a period of 12 weeks, during which T2-weighted magnetic
      resonance images (MRIs) and diffusion-weighted MRIs (DWIs) were collected at
      weeks 1, 3, 6, 9, and 12. Half the rats (n = 3; and half their age-matched
      littermate controls; n = 3) were then killed for histopathological confirmation
      of the observed VGB-induced cerebellar and cortical white-matter lesions. VGB was
      removed from the diet and additional MRIs of the remaining rats taken at weeks
      14, 17, 20, and 24, at which time they (n = 3), along with remaining controls (n
      = 3), were also killed for histopathology. The T2-weighted MRIs acquired were
      used to compute T2 relaxation time maps. Statistically significant VGB-induced T2
      increases were observed in the frontal and occipital cortices and in the
      cerebellar white matter (CWM). The cerebellar lesions were more clearly discerned
      by eye in the DWIs than by T2-contrast alone. During the recovery period the VGB
      treatment group CWM-T2 and CWM-DWI hyperintensity greatly decreased as the
      reversible lesion disappeared. As expected, histological and immunocytochemical
      examinations demonstrated the presence of intra-myelinic edema, microvacuolation,
      and reactive astrocytosis in the CWM and cortex after 12 weeks VGB-treatment. In
      the remaining animals microvacuolation of the white matter had not completely
      resolved during the 12-week recovery phase. The data show that quantitative MRI
      T2-relaxometry can be used to detect VGB-induced CNS pathology, and also suggest
      that DWI is particularly sensitive to the cerebellar lesion. The reversible
      neurotoxicity of global GABA-elevation in experimental animals is discussed.

PMID- 15150740
TI  - Neurochemical interaction between dopaminergic and noradrenergic neurons in the
      medial prefrontal cortex.
AB  - Growing evidence indicates that there is an interaction between the transmission
      of dopamine (DA) and norepinephrine (NE) in the noradrenergic and dopaminergic
      projections that converge in the medial prefrontal cortex (mPFC). The effects of
      the noradrenergic alpha1 and alpha2 receptors and the NE transporters on the DA
      outflow and those of the dopaminergic D1 and D2 receptors on NE release in the
      mPFC were investigated. Local infusions of NE (90, 150, and 300 nM) into the mPFC
      increased the extracellular release of DA in anesthetized rats. The alpha1
      receptor antagonist (10 microM prazosin), but not the alpha2 receptor antagonist
      (100 microM piperoxan), blocked the NE-induced increase of DA in the mPFC. In
      addition, local infusion of alpha1 receptor agonist (10 microM phenylephrine)
      enhanced DA release in the mPFC. Local application of DA in different
      concentrations into the mPFC increased extracellular NE levels. Intra-mPFC
      infusion of a D1 receptor antagonist (10 nM SCH23390), inhibited the DA-induced
      increase of NE; this did not happen with a D2 receptor antagonist (1 nM
      eticlopride). Local administration of a selective NE uptake inhibitor (1 microM
      desmethylimipramine) into the mPFC increased the outflows of both DA and NE in
      the mPFC. However, co-infusion of DMI and prazosin blunted, but did not totally
      abolish, the DMI-increase in the extracellular levels of DA and NE. These results
      suggest that in the mPFC, 1) extracellular NE could enhance DA release by
      activating the alpha1 receptors; and 2) extracellular DA increased the
      extracellular levels of NE by activating the D1 receptors.

PMID- 15150745
TI  - Micrometer-to-nanometer replication of hierarchical structures by using a surface
      sol-gel process.

PMID- 15150741
TI  - Ultrastructural localization of high-affinity choline transporter in the rat
      neuromuscular junction: enrichment on synaptic vesicles.
AB  - In cholinergic neurons, Na(+)- and Cl(-)-dependent, hemicholinium-3-sensitive,
      high-affinity choline uptake system is thought to be the rate-limiting step in
      acetylcholine (ACh) synthesis. The system is highly regulated by neuronal
      activity; the choline uptake is increased by a condition in which ACh release is
      favored. Here we analyzed the ultrastructural localization of the high-affinity
      choline transporter (CHT) in the rat neuromuscular junctions with two separate
      antibodies. The majority (>90%) of immunogold labeling of CHT was observed on
      synaptic vesicles rather than the presynaptic plasma membrane. Less than 5% of
      the gold-silver particles were associated with the plasma membrane, and more than
      70% of such particles were localized within or in close vicinity to presynaptic
      active zones. Our morphological data support the recent hypothesis that
      trafficking of CHT from synaptic vesicles to the plasma membrane couples neuronal
      activity and choline uptake.

PMID- 15150746
TI  - A new hydrosilylation mechanism--new preparative opportunities.

PMID- 15150747
TI  - Chemically catalyzed asymmetric cyanohydrin syntheses.
AB  - Over the past two decades, significant advances have been made towards developing
      chemically catalyzed asymmetric cyanohydrin syntheses. Preparations that were
      classically highly substrate specific, often using stoichiometric quantities of
      reagents, have been revolutionized by a new generation of catalysts. Methods
      currently available rival, and in many cases surpass, enzymatic procedures in
      terms of synthetic utility, generic applicability, and enantioselectivity. Such
      protocols are increasingly finding application in the syntheses of both
      biologically active natural products and therapeutically important synthetic
      compounds.

PMID- 15150748
TI  - Shear patterning of microdominos: a new class of procedures for making micro- and
      nanostructures.

PMID- 15150749
TI  - Well-defined carbon nanoparticles prepared from water-soluble shell cross-linked
      micelles that contain polyacrylonitrile cores.

PMID- 15150750
TI  - [SiNb12O40]16- and [GeNb12O40]16-: highly charged Keggin ions with sticky
      surfaces.

PMID- 15150751
TI  - A family of supramolecular frameworks of polyconjugated molecules hosted in
      aromatic nanochannels.

PMID- 15150752
TI  - A robust porous material constructed of linear coordination polymer chains:
      reversible single-crystal to single-crystal transformations upon dehydration and
      rehydration.

PMID- 15150753
TI  - A dimeric manganese(III) tetradentate schiff base complex as a single-molecule
      magnet.

PMID- 15150755
TI  - Enzymatic synthesis of redox-labeled RNA and dual-potential detection at DNA
      modified electrodes.

PMID- 15150754
TI  - Light-activated transfer of nitric oxide from a porous material.

PMID- 15150756
TI  - Reductive electrochemical cyclization of a photochromic 1,2-dithienylcyclopentene
      dication.

PMID- 15150757
TI  - Asymmetric hydrogenation of ketones catalyzed by RuII-bicp complexes.

PMID- 15150758
TI  - Nanoporous metal-containing nickel phosphates: a class of shape-selective
      catalyst.

PMID- 15150759
TI  - Synthesis of rimocidinolide methyl ester, the aglycone of (+)-rimocidin.

PMID- 15150760
TI  - A 4-exo-dig cyclocarbopalladation/8pi electrocyclization cascade: expeditious
      access to the tricyclic core structures of the ophiobolins and aleurodiscal.

PMID- 15150761
TI  - The transition state of thermal organic reactions: direct observation in real
      time.

PMID- 15150762
TI  - Identifying specific conformations by using a carbohydrate scaffold: discovery of
      subtype-selective LPA-receptor agonists and an antagonist.

PMID- 15150763
TI  - MOCVD-loading of mesoporous siliceous matrices with Cu/ZnO: supported catalysts
      for methanol synthesis.

PMID- 15150764
TI  - Bis(fluoroformyl)trioxide, FC(O)OOOC(O)F.

PMID- 15150765
TI  - Intramolecular C-H activation in complexes with Mo-Bi metal bonds.

PMID- 15150766
TI  - Efficient asymmetric hydrogenation of pyridines.

PMID- 15150767
TI  - Determination of the absolute chirality of adsorbed molecules.

PMID- 15150769
TI  - Knowledge without truth: screening for complications of neurofibromatosis type 1
      in childhood.

PMID- 15150770
TI  - Outcomes of systematic screening for optic pathway tumors in children with
      Neurofibromatosis Type 1.
AB  - Optic pathway tumors (OPT) occur in about 15% of individuals with
      Neurofibromatosis Type 1 (NF1) and may effect substantial visual loss. Because
      their growth is not predictable at the time of discovery, neuroimaging for OPT in
      asymptomatic NF1 patients remains controversial. We evaluated the outcomes of
      systematic screening by both MRI and ophthalmic examinations for OPT in young
      children with NF1 seen at multi-disciplinary clinics for Neurofibromatosis and
      Genetics at one institution between 1996 and 2001. We report on 84 children who
      presented with NF1 under age 6 years, of whom 13 children presented with either
      known OPT or abnormal MRI findings and 11 children had OPTs identified by
      neuroimaging, including two children with abnormal eye examinations at
      presentation (one with strabismus and one with optic atrophy). Nine OPTs were
      detected in asymptomatic subjects with normal ophthalmic examinations. Three
      children with chiasmal lesions enlarging on subsequent MRI were treated with
      carboplatin and vincristine. After treatment, the vision in each involved eye was
      intact. In contrast, the 13 children with OPT diagnosed outside of screening
      guidelines included five children with substantial visual loss. Our observations
      suggest that early recognition of NF1 promotes appropriate surveillance and
      allows early intervention to reduce complications of OPT. This analysis supports
      prospective studies to compare the outcomes of systematic screening with
      neuroimaging to screening with ophthalmic examinations alone in children with
      NF1.

PMID- 15150771
TI  - DNA studies of mono- and pseudodicentric isochromosomes 18q.
AB  - The description of isochromosomes 18 has so far mainly been by cytogenetic
      studies and based on identical banding pattern of the two arms. However, only
      molecular techniques are capable to distinguish an isochromosome from a
      translocation, whole arm or reciprocal, between two chromosomes 18. We have used
      23 PCR-based DNA polymorphisms to determine the parental origin and mechanisms of
      formation in four patients with isochromosomes 18q and to demonstrate that they
      were consistent with true isochromosomes. Three of the probands were liveborn
      children with clinical features characteristic of Edwards syndrome, one proband
      was a fetus diagnosed at prenatal diagnosis. In one case the isochromosome was
      monocentric with two identical q arms of maternal origin, formed by misdivision
      of the centromere and loss of p arm material. Another monocentric case had 47
      chromosomes with isochromosomes i(18p) and i(18q) formed by maternal postzygotic
      centromeric misdivision and segregation of both isochromosomes, or by meiosis II
      centromeric misdivision and nondisjunction (without recombination in meiosis I).
      In two cases, the isochromosomes were dicentric with genetically identical arms
      composed of a part of the short and the whole long arm of chromosome 18 of
      paternal origin. The formation of the fused chromosomes can be explained by
      postzygotic exchange of sister chromatids on the short arm of chromosome 18,
      followed by breakage and U-shape reunion of sister chromatids.

PMID- 15150772
TI  - Risk of sudden death in the Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome (WBS) is a genetic disorder characterized by a
      distinctive facial gestalt, mental retardation, mild growth deficiency, and
      cardiovascular disease. The occurrence of sudden death in the WBS is known from
      several case reports, but information about the risk of sudden death as derived
      from the data of a large cohort of patients is lacking. We analyzed the data of
      293 WBS patients who had been treated for 43 years at the same two institutions.
      We thus collected 5,190 patient years without loss to follow-up. During this
      period ten patients died. Five of them died from: reticulosarcoma (1), after
      accident (1), heart failure (1), following heart surgery (2). Of the remaining
      five patients, four died suddenly and one died of unknown cause suggestive of
      sudden cardiac death. Thus, the incidence of sudden death in our WBS cohort
      amounts to 1/1,000 patient years. This risk of sudden death is comparable to that
      following surgery for congenital heart disease, and is 25-100-fold higher
      compared to the age-matched normal population.

PMID- 15150773
TI  - Psychotic disorders in Prader-Willi syndrome.
AB  - The Prader-Willi syndrome (PWS) is a genetically determined developmental
      disorder caused by abnormalities of the proximal region of chromosome 15q11-13.
      In a previous study, we reported that psychotic episodes, occurring in 16% of
      persons with PWS, had an onset in adolescence, never occurred in persons with
      paternal deletion, and were exclusively associated with maternal uniparental
      disomy (UPD) or imprinting abnormalities (IM). In order to gain a better
      understanding of the psychopathology and to further refine the psychiatric
      diagnosis, we describe in more detail the psychopathological manifestations of
      six adults with a history of psychotic episodes. All these individuals had a
      detailed psychiatric examination, including the use of the operational criteria
      (OPCRIT) checklist. An identifiable subtype of psychotic disorder was associated
      with PWS. Characteristics include early age of onset, acute onset, polymorphous,
      and shifting symptomatology and a need for psychiatric hospitalization. The
      presence of precipitating stress factors and a prodromal phase with physiological
      symptoms was reported in all patients. Current diagnostic categories do not allow
      an unequivocal psychiatric diagnosis.

PMID- 15150774
TI  - Identification of mutations in TCOF1: use of molecular analysis in the pre- and
      postnatal diagnosis of Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial
      development, which results from mutations in TCOF1. TCS comprises conductive
      hearing loss, hypoplasia of the mandible and maxilla, downward sloping palpebral
      fissures and cleft palate. Although, there is usually a reasonable degree of
      bilateral symmetry, a high degree of both inter- and intrafamilial variability is
      characteristic of TCS. The wide variation in the clinical presentation of
      different patients, together with the fact that more than 60% of cases arise de
      novo, can complicate the diagnosis of mild cases and genetic counselling. In the
      current study, we describe how molecular techniques have been used to facilitate
      pre- and postnatal disease diagnoses in 13 TCS families.

PMID- 15150775
TI  - Twenty-four new cases of WT1 germline mutations and review of the literature:
      genotype/phenotype correlations for Wilms tumor development.
AB  - We report here 24 new Wilms tumor (WT) patients with germline WT1 alterations and
      a synopsis of our own previously described and literature cases in whom age of
      tumor-onset, gender, and laterality were known. This combined database contains
      282 patients, 117 patients with and 165 without WT1 germline alterations. Using
      this information we have determined the median age of tumor-onset for patients
      with (12.5 months) and without WT1 gene alterations (36 months). The earliest
      onset was in patients with truncation (12 mo, 66 patients), followed by missense
      mutations (18 mo, 30 patients) and deletions (22 mo, 21 patients). Patients with
      the two most frequent nonsense mutations R362X and R390X and the Denys-Drash
      syndrome (DDS) hot spot mutation R394W/Q/L had a very early onset (9, 12, and 18
      mo, respectively). The highest number of bilateral tumors was observed in the
      group of truncation mutations, with a higher percentage of bilateral tumors when
      truncations occurred in the 5' half of the WT1 gene. In addition to genital tract
      anomalies (GU), early onset nephrotic syndrome with diffuse mesangial sclerosis
      and stromal-predominant histology, tumor bilaterality, and early age of onset can
      now be added to the list of risk factors for carrying a germline WT1 mutation.

PMID- 15150776
TI  - Discordant phenotypes in first cousins with UBE3A frameshift mutation.
AB  - Mutations have been found in the UBE3A gene (E6-AP ubiquitin protein ligase gene)
      in many Angelman syndrome (AS) patients with no deletion, no uniparental disomy,
      and no imprinting defect. UBE3A mutations are more frequent in familial than in
      sporadic patients and the mutations described so far seem to cause similar
      phenotypes in the familial affected cases. Here we describe two first cousins who
      have inherited the same UBE3A frameshift mutation (duplication of GAGG in exon
      10) from their asymptomatic mothers but present discordant phenotypes. The
      proband shows typical AS features. Her affected cousin shows a more severe
      phenotype, with asymmetric spasticity that led originally to a diagnosis of
      cerebral palsy. Proband's brain MRI shows mild cerebral atrophy while her
      cousin's brain MRI shows severe brain malformation. This family demonstrates
      that, although brain malformation is unusual in AS, presence of a brain
      malformation does not exclude the diagnosis of AS. Also, this UBE3A mutation was
      transmitted from the cousin's grandfather to only two sisters among eight full
      siblings, raising the hypothesis of mosaicism for this mutation.

PMID- 15150777
TI  - Large deletion of the GJB6 gene in deaf patients heterozygous for the GJB2 gene
      mutation: genotypic and phenotypic analysis.
AB  - Recent investigations identified a large deletion of the GJB6 gene in trans to a
      mutation of GJB2 in deaf patients. We looked for GJB2 mutations and GJB6
      deletions in 255 French patients presenting with a phenotype compatible with
      DFNB1. 32% of the patients had biallelic GJB2 mutations and 6% were a
      heterozygous for a GJB2 mutation and a GJB6 deletion. Biallelic GJB2 mutations
      and combined GJB2/GJB6 anomalies were more frequent in profoundly deaf children.
      Based on these results, we are now assessing GJB6 deletion status in cases of
      prelingual hearing loss.

PMID- 15150778
TI  - CDKN1C mutation in Wiedemann-Beckwith syndrome patients reduces RNA splicing
      efficiency and identifies a splicing enhancer.
AB  - Wiedemann-Beckwith syndrome (WBS) is a human overgrowth disorder that is
      accompanied by an increased risk of embryonal tumors and is associated with
      dsyregulation of the imprinting of genes in chromosome 11p15.5. Maternally
      inherited mutations in the imprinted CDKN1C gene are known to be associated with
      WBS. We have identified a novel mutation in several members of a large family
      affected by WBS. The mutation is a G --> T change in a run of seven G's near the
      5' splice site of intron 3. All obligate carriers and affected individuals carry
      the mutation, and in each affected case, the allele was inherited maternally,
      strongly suggesting a role in causing WBS. The mutation is located in a poly-G
      tract in the intron; intronic G-rich sequences in other genes have been shown to
      have a role in promoting splicing. In transfected 293HEK cells, we found that the
      G --> T mutation reduced splicing efficiency. Mutation of all seven G's in the
      poly-G tract further reduced splicing efficiency, supporting a role for the G
      tract as a splicing enhancer. The fibroblasts of one affected patient showed a
      similar reduction in splicing efficiency. Maternal monoallelic expression of
      CDKN1C was verified in this patient cell line. However, the total amount of
      spliced message was not reduced by the mutation in spite of the reduced
      efficiency of splicing. We discuss the possible role of the splicing defect in
      the pathogenesis of WBS in this pedigree.

PMID- 15150779
TI  - Mobius sequence, Robin complex, and hypotonia: severe expression of brainstem
      disruption spectrum versus Carey-Fineman-Ziter syndrome.
AB  - We report on nine unrelated children fitting a diagnosis of Carey-Fineman-Ziter
      syndrome (CFZS). All children presented with Mobius sequence, Pierre Robin
      complex (6/9) or micrognathia, and hypotonia. Some had primary hypoventilation,
      delayed development, and acral anomalies. The neuropathological investigations
      performed in two patients showed a combination of dysplastic lesions (neuronal
      heterotopias) and encephaloclastic changes consisting of small foci of necrosis
      with microcalcifications. The mother of a third child had severe trauma during
      her 2nd month of pregnancy. Based on a review of the literature on MS and CFZS,
      we suggest designating as "Robin-Mobius phenotype" a distinct clinical variant of
      MS with extensive brainstem involvement, Robin complex, hypotonia without
      specific muscle disorder, clubfeet and variable acral anomalies. This condition
      appears to bear a higher risk of mental handicap and perhaps a higher recurrence
      risk than "common" MS. Neuropathology and neuroimaging are suggestive, at least
      in some cases, of a vascular disruption, which could be exogenous, or secondary
      to a genetic predisposition. Etiologic heterogeneity seems likely and, in that
      respect, the original CFZS family could represent a private syndrome fitting on
      the "Robin-Mobius" spectrum. Despite the existence of two familial reports,
      recurrence risk is probably much lower than 25%, although exact figures cannot be
      extracted from the available literature.

PMID- 15150780
TI  - Pontine hypoplasia in Carey-Fineman-Ziter (CFZ) syndrome.
AB  - We describe an infant with multiple congenital anomalies including cleft palate
      and micrognathia, Mobius sequence, developmental delay, myopathy, hydronephrosis,
      and bilateral clubfeet. These features are consistent with Carey-Fineman-Ziter
      (CFZ) syndrome (MIM 254940), which has been previously reported in six children
      (including two sibling pairs). Cranial magnetic resonance imaging (MRI) revealed
      an unusually small pons, a finding not previously described in CFZ syndrome.

PMID- 15150781
TI  - Severe congenital myopathy with Mobius, Robin, and Poland sequences: new aspects
      of the Carey-Fineman-Ziter syndrome.
AB  - We report a boy with severe congenital myopathy, Mobius-Poland sequence, Robin
      sequence, and severe developmental delay. We consider this patient to have Carey
      Fineman-Ziter syndrome. Since this is only the seventh case reported, this case
      helps to define further the consistent manifestations of this recognizable
      phenotype. Additionally our patient shows laryngostenosis, intermittent episodes
      of high blood pressure and Poland sequence as important clinical symptoms.

PMID- 15150782
TI  - The Carey-Fineman-Ziter syndrome: follow-up of the original siblings and comments
      on pathogenesis.

PMID- 15150783
TI  - Unusual features in a patient with neurofibromatosis type 1: multiple
      subcutaneous lipomas, a juvenile polyp in ascending colon, congenital
      intrahepatic portosystemic venous shunt, and horseshoe kidney.
AB  - We report a case that draws attention to a hitherto undescribed association of
      neurofibromatosis type 1 (NF1) with juvenile polyp, congenital intrahepatic
      portosystemic venous shunt, multiple subcutaneous lipomas, and horseshoe kidney.
      Our patient has fulfilled the National Institutes of Health consensus conference
      criteria for NF1 by having neurofibromas, axillary freckling, Lisch nodules, and
      cafe-au-lait spots. There is no family history of NF1 and his 7-year-old son has
      no stigmata of NF1. On the other hand, the patient's family had a presumably
      dominant inheritance of horseshoe kidney: the father, proband, sister, and son of
      the other sister had a horseshoe kidney. The patient was investigated for
      mutations in the NF1 gene and PTEN, but no germline mutations were detected. The
      differential diagnosis for such a collection of hamartomatous, cutaneous, and
      vascular disorders includes the Proteus, Bannayan-Riley-Ruvalcaba, and Cowden
      syndromes. None of these diagnoses was convincingly confirmed in this patient.

PMID- 15150784
TI  - FISH characterization of a dicentric Yq (p11.32) isochromosome in an azoospermic
      male.
AB  - The most common structural rearrangements of the Y chromosome result in the
      production of dicentrics. In this work, we analyze an abnormal Y chromosome,
      detected as a mosaic in an azoospermic male ascertained for infertility. FISH
      with seven different DNA probes specific for Y chromosome sequences (Y alpha
      satellite, Y alpha-satellite III, non-alpha-satellite centromeric Y, SRY gene,
      subtelomeric Yp, subtelomeric Yq, and PNA-tel) and CGH analysis were performed.
      FISH results showed that the abnormal Y chromosome was a dicentric Yq
      isochromosome and that the breakpoint was distally in band Yp11.32. Lymphocyte
      chromosomes showed a mosaicism with 46,X,idicY(qter-->p11.32::p11.32-->qter)
      (51.7%), 46,XY (45.6%), and other cell lines (2.7%). In oral interphase cells,
      the mosaicism was 46,XidicY (62.8%), 46,XY (25.7%), 45,X (6.6%), and others
      (4.9%). The possible origin of this dicentric Yq isochromosome is discussed.
      Finally, we compare differences in mosaicism and phenotype among three reported
      cases with the breakpoint at Yp11.32

PMID- 15150786
TI  - Marfanoid habitus with abnormal situs.
AB  - Marfanoid habitus suggests abnormal microfibril formation, whereas a situs
      ambiguus or situs inversus phenotype points to defective left-right axis
      determination. The concurrence of these two abnormalities has been reported only
      once in the literature. We report a similar phenotype in two unrelated patients.
      Documentation of this specific combination of Marfanoid habitus and abnormal
      situs gives further credence to the notion that the combination may represent a
      distinct syndrome.

PMID- 15150785
TI  - Isolated congenital anosmia with morphologically normal olfactory bulb in two
      Iranian families: a new clinical entity?
AB  - Congenital total loss of the sense of smell occurs as a part of a syndrome or
      isolated anosmia. Kallmann syndrome is the most well known congenital anosmia
      associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA)
      is a very rare condition and appears to be due to changes in the olfactory
      epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report
      two unrelated Iranian families with ICA. One family consisted of nine affected
      members, and the other family contained three affected members. Clinical history,
      physical examination, and smell testing by intravenous injection of combined
      vitamins (Alinamin trade mark, Takeda Pharmaceutical Co. Ltd., Japan) confirmed
      the disease in each affected member. No signs of hypogonadism or other
      neurological disorders were observed in any affected members. Family analysis
      with the complete ascertainment method under assumption of the same condition in
      the two families suggested that the disease is not inconsistent with an autosomal
      dominant mode with incomplete penetrance. The inheritance in one family appears
      unusual, i.e., there were no affected individuals in the third generation. When
      only two upper generations in the family are concerned, the segregation ratio was
      0.39 +/- 0.11. Male-to-male transmissions were observed and both sexes were
      affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb
      and sulcus revealed no evidence of morphological changes in all affected members,
      suggesting that these patients have either a defect in the olfactory epithelium
      or a functional defect in the olfactory cortex.

PMID- 15150787
TI  - Clinical, MRI, and pathological features of polymicrogyria in chromosome 22q11
      deletion syndrome.
AB  - Polymicrogyria is a brain malformation due to abnormal cortical organization. Two
      histological types, unlayered or four-layered can be distinguished.
      Polymicrogyria is a rare manifestation of chromosome 22q11 deletion syndrome. We
      report two boys with chromosome 22q11 deletion syndrome and polymicrogyria, and
      describe the neuropathological features of the malformation in one of them.
      Clinical examinations, EEG, brain MRI, chromosomal analysis with FISH, and
      neuropathological studies of surgically resected cortical tissue were performed.
      Both patients showed severe developmental delay with cardiovascular malformations
      and one of them had drug resistant epilepsy. Polymicrogyria was found in the
      frontal, parietal, and temporal areas, unilaterally in one patient and
      bilaterally in the other. Histology revealed four-layered polymicrogyria. The
      pathogenesis of polymicrogyria in 22q11 deletion syndrome is discussed.

PMID- 15150788
TI  - Two sibs with fibrochondrogenesis.
AB  - Fibrochondrogenesis is one of the rare lethal osteochondrodysplasias, which show
      abnormal maturation, and disturbed growth of cartilage and bones. These disorders
      are a heterogenous group of genetic disorders with a total incidence of 1-3 in
      10,000 births. Only 13 cases of fibrochondrogenesis have been published since
      Lazzaroni-Fossati et al. [1978] first described the disorder. We report on two
      sibs that occurred in a consanguineous couple and discuss the ultrasonographic,
      clinical, radiological, and pathological characteristics of this disorder. This
      occurrence confirms autosomal recessive inheritance of fibrochondrogenesis.

PMID- 15150789
TI  - Fine mapping and clinical reevaluation of a Brazilian pedigree with a severe form
      of X-linked mental retardation associated with other neurological dysfunction.

PMID- 15150790
TI  - Genetic heterogeneity in the multiple lentigines/LEOPARD/Noonan syndromes.

PMID- 15150791
TI  - Klippel-Feil anomaly and neural tube defects.

PMID- 15150792
TI  - Macrocephaly, mental retardation, dysmorphism, and spastic paraplegia.

PMID- 15150793
TI  - On the stability of different experimental dimeric structures of the SL1 sequence
      from the genomic RNA of HIV-1 in solution: a molecular dynamics simulation and
      electrophoresis study.
AB  - SL1 is a stem-loop RNA sequence from the genome of HIV-1 thought to be the
      initiation site for the dimerization of the retroviral genomic RNA. The aim of
      this study is to check the stability in solution of different experimental
      dimeric structures available in the literature. Two kinds of dimer have been
      evidenced: an extended duplex looking like a double helix with two internal
      bulges and a kissing complex in which the monomers with a stem/loop conformation
      are linked by intermolecular loop-loop interactions. Two divergent experimental
      structures of the kissing complex from the Lai isolate are reported in the
      literature, one obtained from NMR (Mujeeb et al., Nature Structural Biology,
      1998, Vol. 5, pp. 432-436) and the other one from x-ray crystallography (Ennifar
      et al., Nature Structural Biology, 2001, Vol. 8, pp. 1064-1068). A
      crystallographic structure of the Mal isolate was also reported (Ennifar et al.,
      Nature Structure Biology, 2001, Vol. 8, pp. 1064-1068). Concerning the extended
      duplex, a NMR structure is available for Lai (Girard et al., Journal of
      Biomolecular Structure and Dynamics, 1999, Vol. 16, pp. 1145-1157) and a
      crystallographic structure for Mal (Ennifar et al., Structure, 1999, Vol. 7, pp.
      1439-1449). Using a molecular dynamics technique, all these experimental
      structures have been simulated in solution with explicit water and counterions.
      We show that both extended duplex structures are stable. On the contrary, the
      crystallographic structures of the Lai and Mal kissing complexes are rapidly
      destabilized in aqueous environment. Finally, the NMR structure of the Lai loop
      loop kissing complex remains globally stable over a 20 ns MD simulation, although
      large rearrangements occur at the level of the stem/loop junctions that are
      flexible, as shown from free energy calculations. These results are compared to
      electrophoresis experiments on dimer formation.

PMID- 15150794
TI  - Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+
      channel modulator.
AB  - The solution structure of contryphan-Vn, a cyclic peptide with a double cysteine
      S-S bridge and containing a D-tryptophan extracted from the venom of the cone
      snail Conus ventricosus, has been determined by NMR spectroscopy using a variety
      of homonuclear and heteronuclear NMR methods and restrained molecular dynamics
      simulations. The main conformational features of backbone contryphan-Vn are a
      type IV beta-turn from Gly 1 to Lys 6 and a type I beta-turn from Lys 6 to Cys 9.
      As already found in other contryphans, one of the two prolines--the Pro4--is
      mainly in the cis conformation while Pro7 is trans. A small hydrophobic region
      probably partly shielded from solvent constituted from the close proximity of
      side chains of Pro7 and Trp8 was observed together with a persistent salt bridge
      between Asp2 and Lys6, which has been revealed by the diagnostic observation of
      specific nuclear Overhauser effects. The salt bridge was used as a restraint in
      the molecular dynamics in vacuum but without inserting explicit electrostatic
      contribution in the calculations. The backbone of the unique conformational
      family found of contryphan-Vn superimposes well with those of contryphan-Sm and
      contryphan-R. This result indicates that the contryphan structural motif
      represents a robust and conserved molecular scaffold whose main structural
      determinants are the size of the intercysteine loop and the presence and location
      in the sequence of the D-Trp and the two Pro residues.

PMID- 15150795
TI  - Metastable and stable states of xanthan polyelectrolyte complexes studied by
      atomic force microscopy.
AB  - The compaction of the semiflexible polysaccharide xanthan with selected multi-
      and polyvalent cations was studied. Polyelectrolyte complexes prepared at
      concentrations of 1-2 microg/ml were observed by tapping mode atomic force
      microscopy. High-molecular-weight xanthan compacted with chitosan yields a blend
      of mainly toroidal and metastable structures and a small fraction of rod-like
      species. Polyelectrolyte complexes of xanthan with polyethylenimine and trivalent
      chromium yielded similar structures or alternatively less well packed species.
      Racquet-type morphologies were identified as kinetically trapped states occurring
      on the folding path toward the energetically stable state of the toroids. Thermal
      annealing yielded a shift of the distribution of xanthan-chitosan morphologies
      toward this stable state. Ensembles of toroidal and rod-like morphologies of the
      xanthan-chitosan structures, collected using an asphericity index, were analyzed.
      The mean height of the toroids increased upon heating, with a selective increase
      in the height range above 2 nm. It is suggested that the observed metastable
      structures are formed from the high-molecular-weight fraction of xanthan and that
      these are driven toward the toroidal state, being a low-energy state, following
      annealing. Considered a model system for condensation of semiflexible polymers,
      the compaction of xanthan by chitosan captures the system at various stages in
      the folding toward a low-energy state and thus allows experimental analyses of
      these intermediates and their evolution.

PMID- 15150796
TI  - Statistical mechanics of protein folding with separable energy functions.
AB  - We have initiated an entirely new approach to statistical mechanical models of
      strongly interacting systems where the configurational parameters and the
      potential energy function are both constructed so that the canonical partition
      function can be evaluated analytically. For a simplified model of proteins
      consisting of a single, fairly short polypeptide chain without cross-links, we
      can adjust the energy parameters to favor the experimentally determined native
      state of seven proteins having diverse types of folds. Then 497 test proteins are
      predicted to have stable native folds, even though they are also structurally
      diverse, and 480 of them have no significant sequence similarity to any of the
      training proteins.

PMID- 15150797
TI  - Conformational screening of oligonucleotides by variable-temperature high
      performance liquid chromatography: dissecting the duplex-hairpin-coil equilibria
      of d(CGCGAATTCGCG).
AB  - This study probes the potential of variable-temperature high performance liquid
      chromatography (VT-HPLC) as a tool for dissecting and modulating nucleic acid
      structural transitions, using as a model the duplex-hairpin-coil transitions of
      d(CGCGAATTCGCG). It is demonstrated that VT-HPLC, combined with diode-array
      detection of the uv signal, enables, for the first time, a physical separation of
      spectroscopically distinct species that can be assigned to the duplex, hairpin,
      and coil forms of d(CGCGAATTCGCG). Although the species are spectroscopically
      distinguishable, they are not readily isolated. Hence, if fractions from the
      peaks for hairpin or duplex forms are collected and subsequently reinjected onto
      the cartridge, reequilibration occurs, and both hairpin and duplex peaks are
      observed. Area integration of the peaks corresponding to duplex and hairpin
      species provides a means to monitor the duplex to hairpin transition at effective
      concentrations in the nanomolar range, well below that accessible by conventional
      spectrophotometers. Concentration-dependent equilibrium constants, melting
      temperatures, and standard state enthalpies extracted from our measurements
      compare very well with previous literature results, and with our own results that
      take into account the effect of our solvent conditions [100 mM TEAA
      (triethylammonium acetate) and variable acetonitrile] on the melting behavior. By
      combining precise temperature control with separation based on size, physical
      behavior, and interaction free energies, VT-HPLC provides a powerful tool for
      both the modulation and the separation of nucleic acid conformations.

PMID- 15150799
TI  - Structure and solvation of melittin in hexafluoroacetone/water.
AB  - Intermolecular (1)H[(19)F] and (1)H[(1)H] nuclear Overhauser effects have been
      used to explore interaction of solvent components with melittin dissolved in 50%
      hexafluoroacetone trihydrate (HFA)/water. Standard nuclear Overhauser effect
      experiments and an analysis of C(alpha)H proton chemical shifts confirm that the
      conformation of the peptide in this solvent is alpha-helical from residues Ala4
      to Thr11 and from Leu13 to Arg24. The two helical regions are not collinear; the
      interhelix angle (144 +/- 20 degrees ) found in this work is near that observed
      in the solid state and previous NMR studies. Intermolecular NOEs arising from
      interactions between spins of the solvent and the solute indicate that both
      fluoroalcohol and water molecules are strongly enough bound to the peptide that
      solvent-solute complexes persist for > or =2 ns. Preferential interactions of HFA
      with many hydrophobic side chains of the peptide are apparent while water
      molecules appear to be localized near hydrophilic side chains. These results
      indicate that interactions of both HFA and water are qualitatively different from
      those present when the peptide is dissolved in 35% hexafluoro-2-propanol/water, a
      chemically similar helix-supporting solvent system.

PMID- 15150798
TI  - Inner-sphere complexes of divalent cations with single-stranded poly(rA) and
      poly(rU).
AB  - A combination of ultrasound velocimetry, density, and UV spectroscopy has been
      employed to study the hydration effects of binding of Mn(2+) and alkaline-earth
      cations to poly(rA) and poly(rU) single strands. The hydration effects, obtained
      from volume and compressibility measurements, are positive due to overlapping the
      hydration shells of interacting molecules and consequently releasing the water
      molecules to bulk state. The volume effects of the binding to poly(rA),
      calculated per mole of cations, range from 30.6 to 40.6 cm(3) mol(-1) and the
      compressibility effects range from 59.2 x 10(-4) to 73.6 x 10(-4) cm(3) mol(-1)
      bar(-1). The volume and compressibility effects for poly(rU) are approximately 17
      cm(3) mol(-1) and approximately 50 x 10(-4) cm(3) mol(-1) bar(-1), respectively.
      The comparative analysis of the dehydration effects suggests that the divalent
      cations bind to the polynucleotides in inner-sphere manner. In the case of
      poly(rU) the dehydration effects correspond to two direct coordination, probably
      between adjacent phosphate groups. The optical study did not reveal any effects
      of cation on the secondary structure or aggregation of poly(rU). In the case of
      single-helical poly(rA) binding is more specific: dehydration effects correspond
      to three to five direct contacts and must involve atomic groups of adenines, and
      the divalent cations stabilize and aggregate the polynucleotide.

PMID- 15150800
TI  - Synthesis and characterization of poly(dimer acid-brassylic acid) copolymer and
      poly(dimer acid-pentadecandioic acid) copolymer.
AB  - Poly(dimer acid-brassylic acid) [P(DA-BA)] copolymers and poly(dimer acid
      pentadecandioic acid) [P(DA-PA)] copolymers were prepared by melt
      polycondensation of the corresponding mixed anhydride prepolymers. The copolymers
      were characterized by Fourier transform infrared (FTIR), gel permeation
      chromatography (GPC), differential scanning calorimetry (DSC), wide angle x-ray
      powder-diffraction, and thermal gravimetric analysis (TGA). In vitro studies show
      that all the copolymers are degradable in phosphate buffer at 37 degrees C, and
      leaving an oily dimer acid residue after hydrolysis for the copolymer with high
      content of dimer acid. The release profiles of hydrophilic model drug,
      ciprofloxcin hydrochloride, from the copolymers, follow first-order release
      kinetics. All the preliminary results suggested that the copolymer might be
      potentially used as drug delivery devices.

PMID- 15150801
TI  - Competition of drugs to serum albumin in combination therapy.
AB  - The mechanism of cooperative binding of both cytarabine and fluorouracil, used in
      combination therapy, to the transporting protein [bovine serum albumin (BSA)] has
      been investigated. Present study shows a strategy of estimating the kind of
      competition between these drugs with the use of uv and NMR spectroscopy. Two
      mechanisms of the competition to the transporting protein are proposed. For the
      quantitative investigations the effect of the protein on both the line width and
      chemical shifts of the NMR signals of the 5-fluorouracil and cytarabine was
      analyzed. The pi-pi interaction between the pyrimidine ring of the drugs and the
      aromatic residues of the protein has been postulated. The binding site for both 5
      fluorouracil and cytarabine on BSA was found to be situated in the hydrophobic
      IIA subdomain. The competition of these two drugs and the removal of 5
      fluorouracil by cytarabine from the common binding site in serum albumin tertiary
      structure are observed.

PMID- 15150802
TI  - Fluorescence spectral properties of labeled thiolated oligonucleotides bound to
      silver particles.
AB  - We examined the fluorescent spectral properties of fluorescein-labeled DNA
      oligomers when directly bound to metallic silver particles via a terminal
      sulfhydryl group. We found a 12-fold increase in fluorescence intensity and 25
      fold decrease in lifetime for a fluorescein residue positioned 23 nucleotides
      from the silver surface compared to labeled oligomers in free solution. Similar
      results were found for a 23-mer labeled with five fluorescein residues. The
      absence of long lifetime components in the intensity decays suggests that all
      labeled oligomers are bound to silver and affected similarly by the metallic
      surfaces. These results provide the basic knowledge needed to begin use of metal
      enhanced fluorescence for the detection of target sequences in simple formats
      potentially without a washing separation step. The use of metal-enhanced
      fluorescence provides a generic approach to obtaining a hybridization-dependent
      increase in fluorescence with most, if not all, commonly used fluorophores.

PMID- 15150805
TI  - The Charcot foot: historical perspective 1827-2003.
AB  - Charcot's joint disease of the foot and ankle is a poorly understood and
      frequently overlooked complication of diabetes. Recognition of this condition,
      especially in its earliest stage, remains problematic, with many cases going
      misdiagnosed even today. Medical management of the Charcot foot remains the
      standard of care for the majority of patients, with surgical intervention
      reserved for the most difficult cases. This historical perspective began in the
      early nineteenth century with the first attempts to experimentally examine the
      spinal origin of rheumatism of the foot and ankle. J.-M. Charcot was the first to
      describe the arthropathies associated with tabes dorsalis. His early
      investigations into the tabetic arthropathies (1868) and his brilliant
      presentation, Demonstration of Arthropathic Affections of Locomotor Ataxy, at the
      7th International Medical Congress (1881), established this disease as a distinct
      pathological entity. Charcot and Fere published the first observations of the
      tabetic foot (Pied tabetique) in the Archives de Neurologie in 1883. It was not
      until 1936, however, that W. R. Jordan established the association between
      neurogenic arthropathy of the foot/ankle and diabetes mellitus.

PMID- 15150806
TI  - The diabetic foot, 2003.
AB  - Over the last 20 years, there has been considerable progress in the care of the
      diabetic foot. The increased limb survival rate in patients attending multi
      disciplinary clinics has resulted from advances in the care of the neuropathic
      foot, the neuro-ischaemic foot and from advances in the management of infection.
      However, significant concerns still remain, requiring a call to action.

PMID- 15150807
TI  - Psychological aspects of diabetic neuropathic foot complications: an overview.
AB  - Despite recent advances in understanding and major efforts to control the
      biomedical risk factors for neuropathic foot complications, the rates of foot
      ulceration and amputation remain unacceptably high. As the current focus on
      physical factors alone has not led to a substantial decline in foot complications
      in persons with diabetes, we propose a more balanced approach with the
      consideration of potentially important psychological factors. Until recently,
      psychosocial research in diabetes has almost exclusively focused on self-care
      behaviours and the burdens associated with the management of glycaemia, almost to
      the total neglect of the effects of chronic complications including neuropathy.
      As the burdens associated with the complications of diabetes begin to overshadow
      those specific to the control of glycaemia, it is important to develop social and
      psychological concepts and measures that capture how patients perceive and
      respond to specific threats such as that of neuropathy. There is now some
      progress in this area as evidenced by emerging patient-centred, theory-based
      methods to identify psychological factors influencing adherence behaviours,
      emotional status and quality of life in diabetic patients at high risk of
      developing foot ulcers. The development of a conceptual model of patient's common
      sense representations or beliefs about foot complications and the type and source
      of their emotional distress should allow clinicians and behavioural investigators
      to share ideas for the assessment of patient beliefs and behaviour, and the
      development of educational methods that should improve clinicians' ability to
      empower patients to manage their neuropathy more efficiently.

PMID- 15150808
TI  - Specific problems of the diabetic foot in developing countries.
AB  - As in many developed countries, diabetic foot disease is also resulting in major
      debilitating complications with severe morbidity and possible amputations in many
      developing countries. The developing countries, however, have certain specific
      cultural and social habits that may put a person with diabetes at a higher risk.
      The high prevalence of neuropathy promotes recurrence of foot infections and
      these are seldom treated adequately. Lack of facilities in nearby hospitals and
      unsatisfactory metabolic control are major contributory factors for foot
      problems. Regular inspection of the feet for signs of neuropathy and other risk
      factors would play a major role in the prevention of these complications. Patient
      education for foot care and early institution of preventive measures by the
      medical practitioners, particularly in view of the high prevalence of neuropathy,
      will help in reducing the morbidity and economic burden from diabetic foot.

PMID- 15150809
TI  - Repetitive ulceration in neuropathic patients.
AB  - METHODS: In a retrospective study, 83 patients with diabetic neuropathic foot
      ulceration were classified into two groups: those with a higher rate of
      ulceration defined as >/=3.5 ulcers per foot per 10 years (group H) and those
      with a lower rate of <3.5 ulcers per foot per 10 years (group L). RESULTS: Higher
      risk was associated with neuroarthropathy, higher mean HbA(1c), men who lived
      alone, alcohol misuse by men, poor compliance with footwear, footcare and with
      non-foot aspects of diabetic self-care, higher non-attendance rates and, in
      patients with type 1 diabetes, delay in reporting new foot problems. CONCLUSIONS:
      Reduction in ulcer recurrence rates will require improved orthotic provision in
      patients with neuroarthropathy and new methods to achieve behavioural change in
      other higher risk patients.

PMID- 15150810
TI  - Diagnostic and therapeutic arterial interventions in the ulcerated diabetic foot.
AB  - Whether diabetic foot ulcerations arise from an amalgam of neuro-ischemic factors
      or because of arterial occlusive disease alone, the arterial circulation must be
      thoroughly evaluated. Clinical evaluation is foremost, but numerous non-invasive
      diagnostic options such as duplex ultrasonography and MRA are often enlisted.
      Contrast arteriography remains unrivaled for delineating the causative occlusive
      lesions and the possibilities for arterial reconstruction. The principal
      revascularizations, in our experience, are (1) pedal bypass with autogenous
      conduits and (2) iliacafemoral endarterectomy. Nearly all diabetic patients
      (>90%) and a majority of diabetic patients on hemodialysis are candidates for
      arterial reconstruction, with a resulting three-year limb-salvage rate of 85 to
      90%. No matter how good the foot care and the off-loading is, the arterial
      lesion(s) (5) must be repaired in the overwhelming majority of patients to
      achieve sustained healing. Unfortunately the five-year survival of these diabetic
      patients is usually <50%.

PMID- 15150811
TI  - Corrective surgery in diabetic foot deformity.
AB  - Corrective surgery in the diabetic foot has been used increasingly in the past
      decade. Several benchmarking studies indicate that up to half of patients with
      Charcot deformity of the foot due to diabetes eventually undergo surgery,
      although most textbooks recommend lengthy conservative treatment. Surgical
      procedures reported in diabetic foot deformity are great toe amputation,
      metatarsal head resection/osteotomy, arthrodesis at different levels with a large
      variety of internal and external fixation techniques, and calcanectomy. The
      complication rate in this surgery is high. Most studies are small; all are
      retrospective. Well-controlled quality of life studies comparing alternative
      methods of treatment in Charcot foot deformity are almost entirely lacking.

PMID- 15150812
TI  - Achilles tendon lengthening, the panacea for plantar forefoot ulceration?
AB  - BACKGROUND: Recent reports on Achilles tendon lengthening (ATL) have documented
      rapid healing of chronic plantar neuropathic forefoot ulcers. METHODS: Sixty
      eight patients with 75 ulcerated neuropathic feet (63 patients with diabetes with
      69 ulcerated feet) underwent ATL and were retrospectively studied for chronic
      plantar ulceration in the forefoot and reduced dorsiflexion range of motion at
      the ankle. Median duration of ulcers was 48 months (range 11-84 months) in 16
      forefoot amputation stumps and 11 months (range 3-84 months) for the rest of the
      patients. RESULTS: Healing of the ulcers was obtained in 68/75 feet (91%). At a
      median follow-up of 12 months (3-26 months), 4 had never healed, 5/10 recurrent
      ulcers and 6/11 transfer ulcers (localized to the heel) had not healed, that is,
      a healing rate of 60/75 (80%). Acute transfer ulcers to the heel occurred in 47%
      of patients with complete anaesthesia of the heel pad. Late heel ulceration
      occurred in 14% of those with extreme ankle dorsiflexion (>15 degrees). Failure
      to heal or ulcer recurrence occurred more frequently at dorsiflexion <10 degrees
      (33%). Rupture of the Achilles tendon occurred in 7 feet (10%). Charcot event was
      experienced in 3 (4%). CONCLUSION: Lengthening of the Achilles tendon is
      effective in healing plantar neuropathic ulceration. Patients with complete
      anaesthesia of the heel pad should not undergo this procedure and extreme
      dorsiflexion should be avoided because of the risk of heel ulceration. Moreover,
      the procedure should be performed only in a multidisciplinary setting for
      immediate dealing with complications and for surveillance and treatment of future
      ulceration.

PMID- 15150813
TI  - Surgical treatment of the infected diabetic foot.
AB  - OBJECTIVES: In the treatment of a septic diabetic foot, you have to differentiate
      between a septic foot with and without ischemia. Clinical and non-invasive
      investigations are essential for this differentiation. The initial treatment is
      the same: surgical debridement and antibiotics. For foot debridement, anatomic
      knowledge is mandatory because massive edema can lead to a compartment syndrome
      of the plantar side of the foot. In case of ischemia, aggressive
      revascularization procedures, endovascular, surgical, or a combination should be
      performed to create adequate blood supply to the foot. METHODS: In a
      retrospective analysis, 150 patients were reviewed. RESULTS: In this approach, a
      two-year limb-salvage rate is more than 81.1% with a two-year patency of 62%. A
      primary amputation should be considered in case of a pre-operative mobility grade
      4 or 5 (wheelchair dependency and bedridden, not able to move around).
      CONCLUSIONS: With aggressive treatment with or without revascularisation
      procedures, limb salvage of >80% can be achieved in the infected diabetic foot.

PMID- 15150814
TI  - Lower-extremity amputations in patients with diabetes: pre- and post-surgical
      decisions related to successful rehabilitation.
AB  - BACKGROUND: Peripheral vascular disease and diabetes account for the majority of
      lower-extremity amputations in the adult population. Whenever a patient presents
      to a surgeon regarding a diseased limb, the initial basic decision is to
      determine whether to attempt limb salvage or proceed with an amputation.
      Unfortunately, limb salvage is not an option for many of these patients. Once
      amputation is chosen as a treatment option, the optimal level of amputation has
      to be determined by the surgeon, who is then faced with selecting the optimal
      level of amputation compatible with wound healing and subsequent prosthetic
      fitting. METHODS: Methods for objectively determining optimal amputation level
      include vascular evaluations, assessing the level of cellulites or osteomyelitis,
      or intra-operatively, by looking at the amount of bleeding in skin flaps.
      RESULTS: The net outcome is that there is currently no universally accepted
      method for determining the level of amputation for successful wound healing or
      for preventing subsequent higher amputations. CONCLUSIONS: What is generally
      recognized is that there are disparities in the rates of amputation for type 1
      versus type 2 diabetic patients, for different ethnic groups and for patients
      with multiple co-morbidities. However, with advances in surgical techniques and
      with modern prosthetics, all categories of patients are benefiting from surgeries
      in which a longer residual limb can be kept (within surgical constraints related
      to proper wound healing), and where appropriate biomechanical considerations are
      taken into account.

PMID- 15150815
TI  - Therapeutic footwear for people with diabetes.
AB  - In this review, the evidence for the role of footwear in causing, healing, and
      preventing foot ulceration in diabetic patients is discussed. The mechanisms of
      action of therapeutic footwear are elucidated, and an 'ideal' approach to
      footwear prescription is outlined. Finally, some future directions for
      'intelligent' footwear are also presented.

PMID- 15150816
TI  - Diagnosing and treating diabetic foot infections.
AB  - Foot infections are a common, complex and costly complication of diabetes. We
      have made considerable progress in establishing consensus definitions for
      defining infection. Similarly, we have learned much about the appropriate ways to
      diagnose both soft tissue and bone infections. Accompanying these advances have
      been improvements in our knowledge of the proper approaches to antibiotic (and
      surgical) therapy for diabetic foot infections. Furthermore, investigators have
      explored the value of various adjunctive therapies, especially granulocyte colony
      stimulating factors and hyperbaric oxygen, for improving outcomes. This paper
      presents a summary of a minisymposium on infection of the diabetic foot that was
      held at the fourth International Symposium on the Diabetic Foot, in
      Noordwijkerhout, The Netherlands.

PMID- 15150817
TI  - Introduction to consensus projects.

PMID- 15150818
TI  - A report from the international consensus on diagnosing and treating the infected
      diabetic foot.
AB  - In persons with diabetes, foot infection, that is, invasion and multiplication of
      microorganisms in tissues accompanied by tissue destruction or a host
      inflammatory response, usually begins with skin trauma or ulceration 1. While
      most foot infections remain superficial, they can spread to subcutaneous tissues,
      including muscle, joints, and bone. Many diabetic foot ulcers eventuate in an
      amputation; infection plays a role in approximately 60% of cases 2-4. Neuropathy
      is the main factor leading to skin breaks, while arterial perfusion largely
      affects infection outcome. Among the factors predisposing diabetic patients to
      foot infections are ill-defined immunological perturbations 56; foot anatomy may
      foster proximal spread of infection and ischemic necrosis 78.

PMID- 15150819
TI  - Wound healing and treatments for people with diabetic foot ulcers.
AB  - The factors that delay wound healing are multiple and relate both to diabetes and
      to the effect of its complications. Diabetic foot ulcers readily become chronic,
      and chronic ulcers have biological properties that differ substantially from
      acute ones. Much of the available information on the biology of wound healing
      relates to acute and experimental wounds and may not be directly relevant. It
      follows that there is limited evidence currently available to underpin protocols
      for the management of diabetic foot ulcers, or to guide choice of applications
      and dressings 1. Nevertheless, it is possible to define certain
      principles.GLYCAEMIC CONTROL: The first relates to glycaemic control. While
      chronic complications of diabetes such as peripheral vascular disease and
      neuropathy may be largely irreversible, aspects of structure and function of
      connective tissue and cells may be impaired by hyperglycaemia, and their function
      should be improved if normoglycaemia is achieved. PROMOTION OF HEALING: The
      second principle concerns attempts at active promotion of wound healing by (1)
      surgical revascularization, and (2) specific attempts to correct defined
      biological abnormalities thought to be hindering the healing process. These
      include the use of a variety of applications, dressings and technologies, which
      may stimulate healing by applying, or stimulating the release of, growth factors
      and cytokines. While this approach holds the greatest promise for the future, it
      will be dependent on defining defects which need correction in specific
      individuals, and having technologies available to address them. This field is in
      its infancy. WOUND CARE: The third broad principle concerns the management of the
      wound and its surrounding tissue in order to promote healing. This includes
      regular inspection, cleansing and removal of surface debris, elimination of
      pathogenic bacteria and creation of an appropriate environment to facilitate
      endogenous tissue regeneration. There are many applications and dressings that
      may be chosen to promote healing, but, whichever is selected, wound management
      has to be integrated into an effective programme of multidisciplinary care.

PMID- 15150820
TI  - Diabetic foot ulcer classification system for research purposes: a progress
      report on criteria for including patients in research studies.
AB  - Various different systems have been proposed to classify diabetic foot ulcers,
      but none has gained widespread acceptance. The International Working Group of the
      Diabetic Foot (IWGDF) developed a classification system for research purposes,
      which is described in this report. In this PEDIS system, all foot ulcers should
      be classified according to five categories: perfusion, extent/size, depth/tissue
      loss, infection and sensation. The methods to determine the presence and severity
      of these factors are described; each (sub)category is defined according to strict
      criteria, which are applicable worldwide. All experts involved and all members of
      the IWGDF reached consensus on this system, which will be validated first, before
      it can be formally introduced.

PMID- 15150822
TI  - The formation of RCCCO and CCC(O)R (R = Me, Ph) neutral radicals from ionic
      precursors in the gas phase: the rearrangement of CCC(O)Ph.
AB  - Neutrals MeCCCO, CCC(O)Me, PhCCCO and CCC(O)Ph have been made by neutralisation
      of [MeCCCO](+), [CCC(O)Me](-), [PhCCCO](+) and [CC(CO)Ph](-). Neutrals MeCCCO,
      CCC(O)Me and PhCCCO are stable for the microsecond duration of the neutralisation
      experiment. A joint experimental and theoretical study (energies calculated at
      the B3LYP/aug-cc-pVDZ//B3LYP/6-31G(d) level of theory) suggests that the neutral
      radical CCC(O)Ph rearranges via a four-centred ipso radical cyclisation/ring
      opening to form the isomer PhCCCO in an exothermic reaction. (13)C labelling
      confirms that the rearrangement does not involve O migration. Some of the PhCCCO
      radicals formed in this reaction are sufficiently energised to effect
      decomposition to give PhCC and CO.

PMID- 15150821
TI  - Use of isotopically labelled octanoic acid to assess the effect of meal size on
      gastric emptying.
AB  - It has been proposed that the (13)C-octanoic acid breath test (OBT) provides a
      safe, non-radioactive means of measuring gastric emptying. However, deuterated
      octanoic acid provides a better marker when compared with scintigraphy, as the
      kinetics are less complex than those of the (13)C label. The appearance of (2)H
      in saliva is modelled as a two-compartment body water system, using an asymmetric
      triangular gastric emptying function. This study compared the (2)H-octanoic acid
      saliva test (OST) with the OBT in measuring altered states of gastric emptying in
      the nutritional context of diet manipulation. Gastric emptying was measured using
      the OST and OBT in a three-way crossover study involving 12 healthy male and
      female subjects (mean BMI = 23.4 kg/m(2), aged 24-57 years). Following an
      overnight fast, subjects were given an egg meal, labelled with 10 microL/kg body
      weight (2)H-octanoic acid and 100 microL (13)C-octanoic acid. The meal was
      nutritionally manipulated to provide a 1 MJ, 2 MJ or 3 MJ meal. Breath and saliva
      samples were collected at regular intervals for 6 h, with further saliva samples
      being collected over four subsequent days. (2)H isotopic enrichment in saliva and
      (13)C isotopic enrichment in breath were analysed using isotope ratio mass
      spectrometry and the data fitted to the respective gastric emptying models. The
      half excretion time (T(1/2) (D)), time to maximum emptying rate (T(1) (D)) and
      time when emptying is complete (T(2) (D)) were calculated from the (2)H saliva
      test data, and the lag time (T(lag) (C)), half excretion time (T(1/2) (C)),
      latency phase (T(lat) (C)) and ascension time (T(asc) (C)) were calculated from
      the (13)C breath test data. Overall, the OBT correlated well with the OST, with a
      significant relationship between T(1/2) (C) and T(1/2) (D), a significant
      relationship between T(lat) (C) and T(1) (D) and finally a significant
      relationship between T(asc) (C) and T(2) (D). Gastric emptying measured using the
      OST was significantly faster with the 1 MJ meal (DeltaT(1/2) (D) = -0.77 h vs. 2
      MJ, p = 0.004). Increases were also seen when the meal size was increased from 2
      MJ to 3 MJ (DeltaT(1/2) (D) = +0.44 h vs. 2 MJ), but these were not significant.
      These trends were mirrored in the OBT data, with significant differences between
      1 MJ and 2 MJ (DeltaT(1/2) (C) = -0.63 h vs. 2 MJ, p = 0.013) and non-significant
      increases with the larger 3 MJ meal (DeltaT(1/2) (C) = +0.10 h vs. 2 MJ). Total
      meal calorie content was shown to have an effect on gastric emptying using both
      the OBT and the OST. The deuterium method allows the direct calculation of the
      gastric emptying function and could be used as an alternative to gamma
      scintigraphy, allowing further validation of the (13)C-octanoic acid breath test.

PMID- 15150823
TI  - Validated procedure for simultaneous trace level determination of the anti-cancer
      agent gemcitabine and its metabolite in human urine by high-performance liquid
      chromatography with tandem mass spectrometry.
AB  - A sensitive, accurate and reproducible procedure has been developed for the
      quantitative determination of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and
      its metabolite 2',2'-difluorodeoxyuridine (2dFdU) in human urine. The samples (2
      mL) were extracted by solid-phase extraction (SPE) and analyzed by reversed-phase
      high-performance liquid chromatography coupled with tandem mass spectrometry
      (HPLC/MS/MS), operating in multiple reaction monitoring (MRM mode). This
      procedure was validated using 2'-deoxycytidine as internal standard (IS). The
      urine assay was linear over the range 0-50 microg/L, with a limit of
      quantification (LLOQ) of 0.2 microg/L for gemcitabine and 1.0 microg/L for the
      metabolite. The respective limits of detection (LODs) for dFdC and 2dFdU were
      0.05 and 0.3 microg/L. The precision and accuracy of the assay were determined on
      three different days. The within-series precision was found to be always less
      than 8.5 and 12.7% for gemcitabine and 2dFdU, respectively. The overall precision
      expressed as relative standard deviation (CVr) was always less than 7.1% for both
      analytes. The recovery of gemcitabine was always greater than 90% with a CVr
      <6.3%. The measurement uncertainty determined from the validation data assessed
      the possibility of determining this drug and its metabolite at trace levels in
      urine, considering that the combined uncertainty of the whole procedure was
      always less than 30%.

PMID- 15150825
TI  - The analysis of thyroxine in human serum by an 'exact matching' isotope dilution
      method with liquid chromatography/tandem mass spectrometry.
AB  - A method for the analysis of thyroxine in human serum, utilising 'exact matching'
      isotope dilution mass spectrometry (IDMS) in combination with liquid
      chromatography/tandem mass spectrometry (LC/MS/MS), has been developed with a
      limit of quantification of 0.5 ng g(-1) of thyroxine in human serum. The
      extraction and clean-up of thyroxine from serum involves an efficient protein
      precipitation stage followed by a solid-phase extraction procedure to produce an
      extract essentially free from interfering compounds. The method is reproducible,
      with expanded uncertainties of less than 2%, and is relatively fast to perform.

PMID- 15150824
TI  - Nanospray analysis of the venom of the tarantula Theraphosa leblondi: a powerful
      method for direct venom mass fingerprinting and toxin sequencing.
AB  - Mass spectrometric methods, including matrix-assisted laser desorption/ionisation
      time-of-flight mass spectrometry (MALDI-TOFMS), on-line liquid
      chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS), and
      nanospray ionisation/hybrid quadrupole time-of-flight mass spectrometry (nanoESI
      QqTOFMS), were applied to characterize by mass fingerprinting the venom of the
      French Guyanese tarantula Theraphosa leblondi. Of these techniques direct nanoESI
      QqTOFMS, which allowed the detection of 65 protonated molecules with high mass
      accuracy, appeared to give the best results. Three major peptides, TlTx1, TlTx2
      and TlTx3, were sequenced using a combination of nanoESI-MS/MS and enzyme
      digestion/MS and MS/MS experiments. Each sequence was confirmed by automated
      Edman sequencing. In patch-clamp experiments these peptides were found to have a
      specific inhibitory effect on the voltage-dependent potassium channel, Kv4.2.

PMID- 15150826
TI  - Comparison of product ion spectra obtained by liquid chromatography/triple
      quadrupole mass spectrometry for library search.
AB  - Reproducibility of product ion spectra acquired using a liquid
      chromatography/triple-quadrupole mass spectrometry (LC/MS/MS) instrument over a 4
      year period, and with three other LC/MS/MS instruments, one from the same
      manufacturer and two from a different manufacturer, was examined. The MS/MS
      spectra of 30 drug substances were generated in positive electrospray ionization
      mode at low, medium, and high collision energies (20, 35, and 50 eV). Purity and
      Fit score percentages against a 400-compound LC/MS/MS spectral library were
      calculated using an algorithm in which fragment intensity ratios and weighting
      factors were included. The long-term reproducibility study was conducted using a
      brand A instrument; after 4 years the reproducibility of the product ion spectra
      was still 94%, expressed as average Purity score. The inter-laboratory study
      involved two parts. Firstly, two LC/MS/MS spectral libraries, created
      independently in separate laboratories using brand A instruments, were compared
      with each other. The average Fit and Purity scores of spectra from one library
      against the other were better than 93 and 91%, respectively, when the same
      collision energies were used. Secondly, for the comparison of product ion spectra
      between brand A and brand B instruments, fragmentation conditions were first
      standardized for amitriptyline as the standard analyte. The average Fit scores of
      brand B spectra against the brand A spectral library varied between 79 and 85% at
      all three collision energies. These results indicate that, after standardizing
      the instrumental conditions, LC/MS/MS spectral libraries of drug substances are
      suitable for inter-laboratory use.

PMID- 15150827
TI  - Identification by electrospray tandem mass spectrometry of spin-trapped free
      radicals from oxidized 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine.
AB  - GPC radical species formed during oxidation of a glycerophosphocholine
      (16:0/18:1) under the Fenton reaction conditions were detected using a spin trap,
      5,5-dimethyl-1-pyrrolidine N-oxide (DMPO). The stable spin-trapped radical
      adducts were identified by mass spectrometry (MS) using electrospray (ES) as
      ionization method and characterized by tandem mass spectrometry (MS/MS). Radical
      adducts of oxidized free sn-2 fatty acid and of oxidized intact GPC, containing
      one, two and three additional oxygen atoms, were assigned. DMPO adducts of
      oxidized intact GPC were observed as singly and doubly charged ions in ES-MS,
      while adducts of oxidized free fatty acids were observed as singly charged ions.
      Oxidized free sn-2 fatty acids and intact GPC-DMPO adducts correspond to carbon-
      and oxygen-centered radicals that were identified by MS/MS as alkyl, hydroxy
      alkyl, alkoxyl, hydroxy-alkoxyl, peroxyl and hydroperoxide-alkoxyl spin adducts.
      The DMPO molecule was attached predominantly at C(9) of the oleic chain. The
      fragmentation pathway of spin adducts with two DMPO molecules strongly suggests
      the presence of species that were simultaneously carbon- and oxygen-centered
      radicals. Several fragments identified are consistent with the presence of
      isomeric structures contributing to the same ions.

PMID- 15150828
TI  - Derivatization of amino acids with N,N-dimethyl-2,4-dinitro-5-fluorobenzylamine
      for liquid chromatography/electrospray ionization mass spectrometry.
AB  - Derivatization, separation and identification of amino acids with a novel
      compound, N,N-dimethyl-2,4-dinitro-5-fluorobenzylamine (DMDNFB), using high
      performance liquid chromatography/electrospray ionization mass spectrometry
      (HPLC/ESI-MS) was demonstrated. Compared to derivatization with 2,4
      dinitrofluorobenzene (DNFB), DMDNFB-derivatized amino acids and dipeptides
      exhibit much larger ion current signals in the commonly used ESI positive mode,
      which was attributed to the introduction of the N,N-dimethylaminomethyl
      protonatable site.

PMID- 15150829
TI  - Increasing the efficiency of pharmacokinetic sample procurement, preparation and
      analysis by liquid chromatography/tandem mass spectrometry.
AB  - The movement towards a 96-well format has greatly increased productivity and
      throughput in bioanalytical laboratories. Improvements in automated sample
      preparation and analytical methods have further contributed to increased
      productivity. We have focused on sample collection and transfer to the bioanalyst
      and have found improvements to the current available methods. The problem of
      manual transfers and plasma clotting issues can be overcome with the use of
      microtainers. Specifically, for illustrative purposes, three proprietary
      Theravance compounds were tested for stability, non-specific binding, and
      electrospray ion suppression in microtainers. There were no issues with
      stability, non-specific binding or ion suppression for the above compounds even
      after leaving plasma samples in the microtainers over long periods of time. The
      microtainers are robot-compatible and the resulting plasma can be transferred
      without clotting issues. To date, all in-house compounds successfully analyzed
      and tested using the microtainers have mass ranges between 200 and 1800 Da, pK(a)
      ranges between 3.8 and 10.3, and logD ranges between -1.7 and 4.2. Once samples
      are transferred into 96-well plates, flexibility in preparation and analysis is
      available. Together with automated sample preparation and the use of liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) as an analytical tool, the use
      of microtainers as sample collection tubes and for sample storage saved
      considerable time, cost and effort in both of our pharmacokinetic (PK) and
      bioanalytical groups. This in turn has led to an increased efficiency and overall
      throughput in support of our drug discovery effort.

PMID- 15150830
TI  - Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes
      using liquid chromatography/tandem mass spectrometry.
AB  - Following incubation of rutaecarpine, a new cyclooxygenase-2 inhibitor, with rat
      liver microsomes, the structures of the metabolites were characterized by liquid
      chromatography with tandem mass spectrometry. Nine metabolites corresponding to
      mono- or dihydroxylated rutaecarpine were formed. Characteristic product ions for
      the identification of rutaecarpine metabolites were observed at m/z 136, 158 and
      286. The loss of water led to the fragment ion at m/z 286, indicating the
      hydroxylation of the aliphatic ring. The fragment ion at m/z 136 indicated the
      hydroxylated form of the phenyl group of the quinazolinone moiety, while that at
      m/z 158 indicated the hydroxylated form of the aromatic ring of the indole
      moiety.

PMID- 15150831
TI  - Rapid molecular assessment of the bioturbation extent in sandy soil horizons
      under pine using ester-bound lipids by on-line thermally assisted hydrolysis and
      methylation-gas chromatography/mass spectrometry.
AB  - Each plant species has a unique chemical composition, and also within a given
      plant the various tissues differ from one another in their chemistry. These
      different compositions can be traced back after decay of the plant parts when
      they are transformed into soil organic matter (SOM). As a result, the composition
      of SOM reflects not only the plant origin, but also the various tissues, and the
      composition consequently provides an estimate of the contribution of above-ground
      vs. below-ground litter. From the latter distribution the extent of bioturbation
      (mixing of above-ground litter with the mineral soil) can be assessed.
      Application of thermally assisted hydrolysis and methylation (THM) using
      tetramethylammonium hydroxide (TMAH) and subsequent analysis by gas
      chromatography/mass spectrometry (GC/MS) releases all typical cutin- and suberin
      derived aliphatic monomers (mono-, di- and trihydroxyalkanoic acids, alpha,omega
      alkanedioic acids) as their methyl esters and/or ethers in a rapid manner. Using
      the distribution of omega-hydroxyalkanoic acids that are present in pine needle
      cutin (C(12) and C(14)) and not in root suberin, and those that are present in
      roots but not in needles (C(20) and C(22)), the extent of bioturbation (mixing of
      above-ground plant litter with the mineral soil) can be assessed. Similarly, the
      (9,16-dihydroxyhexadecanoic acid+9,10,18-trihydroxyoctadecanoic acid)/(C(20) +
      C(22) alpha,omega-alkanedioic acids) ratio reflects the degree of bioturbation.
      Three mineral soil profiles under Corsican pine with an A horizon that exhibited
      extensive bioturbation phenomena, and underlying C horizons with hardly any or no
      bioturbation, were investigated in order to examine the applicability of such an
      approach. It appeared that the A horizons contained all four mentioned omega
      hydroxyalkanoic acids, while the C horizons contained virtually only the C(20)
      and C(22) members. The results not only suggest that bioturbation occurs in the A
      horizons, but also that possible illuviation or other transport mechanisms of
      omega-hydroxyalkanoic acids seem hardly ever or never to occur, which is a
      prerequisite for applying this biomarker approach in assessing degrees of
      bioturbation.

PMID- 15150832
TI  - Quantitative analysis of eight testosterone metabolites using column switching
      and liquid chromatography/tandem mass spectrometry.
AB  - The rate at which testosterone is metabolized to different singly hydroxylated
      metabolites has been widely used as an in vitro marker for activity of different
      CYP450 enzymes. The interest in extra-hepatic metabolism, e.g. due to metabolism
      in the gut wall, has increased during the last decade. Measurement of extra
      hepatic enzyme activity using testosterone as a substrate requires a highly
      sensitive analytical method. A new liquid chromatography/electrospray tandem mass
      spectrometry (LC/MS/MS) method, using column switching for online cleaning and
      desalting of samples, was developed and validated for analysis of 2alpha-, 2beta
      , 6alpha-, 6beta-, 7alpha-, 16alpha-, and 16beta-hydroxytestosterone and
      androstenedione. The samples were injected on a SB-CN column and detection was
      performed using MS/MS. The limits of quantification ranged from 0.3 to 3.33 nM
      for the different metabolites. The validated method was used to quantify the
      enzyme activity in rat intestine mucosa. The formation rates of 16alpha-, 16beta
      hydroxytestosterone and androstenedione were quantified, and 2beta-and 6beta
      hydroxytestosterone were formed above the limits of detection.

PMID- 15150833
TI  - Mass spectrometric characterization of two novel inflammatory peptides from the
      venom of the social wasp Polybia paulista.
AB  - The social wasp P. paulista is relatively common in southeast Brazil causing many
      medically important stinging incidents. The seriousness of these incidents is
      dependent on the amount of venom inoculated by the wasps into the victims, and
      the characteristic envenomation symptoms are strongly dependent on the types of
      peptides present in the venom. In order to identify some of these naturally
      occurring peptides available in very low amounts, an analytical protocol was
      developed that uses a combination of reversed-phase and normal-phase high
      performance liquid chromatography (HPLC) of wasp venom for peptide purification,
      with matrix-assisted laser desorption/ionization time-of-flight post-source decay
      mass spectrometry (MALDI-Tof-PSD-MS) and low-energy collision-induced
      dissociation (CID) in a quadrupole time-of-flight tandem mass spectrometry (QTof
      MS/MS) instrument for peptide sequencing at the sub-picomole level. The
      distinction between Leu and Ile was achieved both by observing d-type fragment
      ions obtained under CID conditions and by comparison of retention times of the
      natural peptides and their synthetic counterparts (with different combinations of
      I and/or L at N- and C-terminal positions). To distinguish the isobaric residues
      K and Q, acetylation of peptides was followed by Q-Tof-MS analysis. The primary
      sequences obtained were INWLKLGKMVIDAL-NH(2) (MW 1611.98 Da) and IDWLKLGKMVMDVL
      NH(2) (MW 1658.98 Da). Micro-scale bioassay protocols characterized both peptides
      as presenting potent hemolytic action, mast cell degranulation, and chemotaxis of
      polymorphonucleated leukocyte (PMNL) cells. The primary sequences and the
      bioassay results suggest that these toxins constitute members of a new sub-class
      of mastoparan toxins, directly involved in the occurrence of inflammatory
      processes after wasp stinging.

PMID- 15150834
TI  - Coordination chemistry of chromium-Salen complexes studied by electrospray
      ionization mass spectrometry.
AB  - The gas-phase coordination behavior of the [Cr(III)(Salen)]PF(6) complex at the
      free axial positions has been studied in the presence of amines as ligands
      (propylamine and a series of diamines) under electrospray ionization conditions.
      The [Cr(III)(Salen)](+) complex formed stable five- and six-coordinated complex
      ions, [Cr(III)(Salen)(L)](+) and [Cr(III)(Salen)(L)(2)](+), respectively, where L
      = solvent molecule or amine. When diamines were used as ligands, abundant
      [Cr(III)(Salen)(L)](+) ions were observed in which two axial positions of the
      [Cr(III)(Salen)](+) species are occupied by the two amino groups of the diamine
      ligand. The relative abundances of ligated complex ions, fragment ions, and
      solvent adducts of fragment ions in the ESI mass spectra, were found to depend on
      the cone voltage used to record the spectrum. The ESI mass spectra of
      [Cr(III)(Salen)](+) in the presence of diamines as ligands, and experiments on
      ligand-pickup in the collision cell, clearly demonstrated that the
      [Cr(III)(Salen)(L)](+) complex ion is stable for 1,2-diaminoethane and 1,3
      diaminopropane. The stability of [Cr(III)(Salen)(L)](+) ions gradually decreased
      from 1,4-diaminobutane to 1,6-diaminohexane, and then showed a slight increase
      for 1,7-diaminoheptane and 1,8-diaminooctane. The collision-induced dissociation
      spectra of [Cr(III)(Salen)(L)](+) ions support the above observations.

PMID- 15150835
TI  - Negative ion electrospray ionization mass spectral study of dicarboxylic acids in
      the presence of halide ions.
AB  - The negative ion electrospray ionization (ESI) mass spectra of a series of
      dicarboxylic acids, a pair of isomeric (cis/trans) dicarboxylic acids and two
      pairs of isomeric (positional) substituted benzoic acids, including a pair of
      hydroxybenzoic acids, were recorded in the presence of halide ions (F(-), Cl(-),
      Br(-) and I(-)). The ESI mass spectra contained [M--H](-) and [M+X](-) ions, and
      formation of these ions is found to be characteristic of both the analyte and the
      halide ion used. The analytes showed a greater tendency to form adduct ions with
      Cl(-) under ESI conditions compared with the other halide ions used. The isomeric
      compounds yielded distinct spectra by which the isomers could be easily
      distinguished. The collision-induced dissociation mass spectra of [M+X](-) ions
      reflected the gas-phase basicities of both the halide ion and [M--H](-) ion of
      the analyte. However, the relative ordering of gas-phase basicities of all
      analyte [M--H](-) and halide ions could not account for the dominance of chloride
      ion adducts in ESI mass spectra of the analytes mixed with equimolar quantities
      of the four halides.

PMID- 15150836
TI  - Ring contraction reactions of 2,3-dihydro-4H-1,3-oxazin-4-ones under electrospray
      ionization conditions.
AB  - The mass spectral behavior of 2,3-dihydro-4H-1,3-oxazin-4-ones has been
      investigated using electrospray ionization multi-stage mass spectrometry (ESI
      MS(n)). All compounds showed a predominant retro-Diels-Alder (RDA) fragmentation
      pathway, and a novel ring contraction reaction by loss of isocynates was also
      found. The fragmentation mechanisms proposed for 4H-1,3-oxazin-4-ones are
      supported by ESI-MS/MS/MS spectra.

PMID- 15150838
TI  - Discovery of okadaic acid esters in the toxic dinoflagellate Dinophysis acuta
      from New Zealand using liquid chromatography/tandem mass spectrometry.
AB  - The dinoflagellate Dinophysis acuta has been associated with various incidents of
      diarrhetic shellfish poisoning. A sample of Dinophysis acuta collected from New
      Zealand waters in 2002 was previously found to contain high levels of
      pectenotoxins, but only a very low level of the diarrhea-inducing okadaic acid
      (OA). After hydrolysis under basic conditions, however, the concentration of OA
      increased substantially, indicating the presence of conjugated forms of OA. Using
      various liquid chromatography/electrospray ionization tandem mass spectrometry
      (LC/ESI-MS/MS) techniques, a number of OA esters were detected in the original
      extract. The principal compound was identified as a C8 diol-ester of OA (OA-D8),
      which had been identified previously in another dinoflagellate, Prorocentrum
      lima. The retention time, as well as positive and negative ion MS, MS/MS and UV
      spectra of the D. acuta compound, matched exactly those of OA-D8 isolated from P.
      lima. In addition to OA-D8, several other novel OA esters were detected in the D.
      acuta but these have not yet been identified. This is the first report
      identifying the presence of OA esters in Dinophysis species.

PMID- 15150837
TI  - Septin 2 phosphorylation: theoretical and mass spectrometric evidence for the
      existence of a single phosphorylation site in vivo.
AB  - Septins constitute a family of conserved proteins that are required for
      cytokinesis in a wide range of organisms. Most cells express a set of septin
      proteins and these are found to assemble into hetero-oligomeric septin complexes
      that appear filamentous. However, the mechanisms controlling the function and
      polymerization of septins are not known. We therefore examined the possibility
      that septins could be post-translationally modified by phosphorylation. We
      present herein a combined theoretical and experimental approach for the analysis
      of Septin 2 (Sept2) monophosphorylation in vivo. We purified and characterized
      the human recombinant Sept2, a 45-kDa protein, expressed from Sf21 insect cells.
      Analysis by matrix-assisted laser desorption/ionization quadrupole time-of-flight
      mass spectrometry on the full-length protein sequence of wild-type Sept2 revealed
      a unique phosphorylation site at residue Ser248 in vivo, which is consistent with
      one of the twelve phosphorylation sites in the protein sequence theoretically
      predicted by the Netphos program. Additional predictions with the motif scan
      programs Scansite and Prosite suggest that the phosphorylation of wild-type Sept2
      might be a potential substrate for casein kinase 2. Site-directed mutagenesis of
      residue 248 from serine to alanine abrogated this phosphorylation. The location
      of phosphorylation in Sept2 differs from the sites predicted for cGMP-dependent
      protein kinase (PKG) phosphorylation in Septin 3, raising the possibility that
      different septins may undergo distinct phosphorylation events that could control
      their functions in important cellular processes such as neurotransmission or
      cytokinesis.

PMID- 15150839
TI  - The influence of electrospray deposition in matrix-assisted laser
      desorption/ionization mass spectrometry sample preparation for synthetic
      polymers.
AB  - Although electrospray sample deposition in matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) sample preparation increases
      the repeatability of both the MALDI signal intensity and the measured molecular
      mass distribution (MMD), the electrospray sample deposition method may influence
      the apparent MMD of a synthetic polymer. The MMDs of three polymers of differing
      thermal stability, polystyrene (PS), poly(ethylene glycol) (PEG), and
      poly(propylene glycol) (PPG), were studied by MALDI time-of-flight (TOF) MS as
      the electrospray deposition voltage was varied. The MMDs obtained using the
      electrospray deposition method were compared with those obtained for hand-spotted
      samples. No change was observed in the measured polymer MMD when the electrospray
      deposition voltage was varied in the analysis of PS, but those of PEG and PPG
      changed at higher electrospray voltages due to increased ion fragmentation. It
      was also shown that the fragmentation in the hand-spotted samples is dependent on
      the matrix used in sample preparation.

PMID- 15150840
TI  - A rapid and sensitive method for simultaneous determination of lamivudine and
      zidovudine in human serum by on-line solid-phase extraction coupled to liquid
      chromatography/tandem mass spectrometry detection.
AB  - A method based on solid-phase extraction (SPE) coupled to high-performance liquid
      chromatography (HPLC) with positive ion electrospray ionization tandem mass
      spectrometry (ESI-MS/MS) detection was developed for the simultaneous
      determination of lamivudine (3TC) and zidovudine (AZT) in human serum, using
      didanosine (ddI) as internal standard. The acquisition was performed in multiple
      reaction monitoring (MRM) mode, monitoring the transitions m/z 230.0 --> 111.8
      for 3TC, m/z 268.1 --> 126.8 for AZT, and m/z 237.2 --> 136.8 for ddI. The limits
      of detection and quantitation were 3 and 10 ng/mL for 3TC, and 5 and 15 ng/mL for
      AZT. The method was linear in the studied ranges (10-1500 ng/mL for 3TC and 15
      3000 ng/mL for AZT), with r(2) > 0.99 for each drug, and the run time was 4 min.
      The intra-assay precisions (%) were in the ranges 1.9-8.7 (3TC) and 2.2-8.9
      (AZT), the inter-assay precisions were in the ranges 2.6-9.0 (3TC) and 4.2-8.1
      (AZT), and the intra- and inter-assay accuracies were >97% for both drugs. The
      absolute recoveries were 95-99% for 3TC (45, 600 and 1200 ng/mL) and 104-112% for
      AZT (45, 1000 and 2400 ng/mL). The analytical method was applied to a
      bioequivalence study in which 24 healthy adult volunteers received single oral
      doses of the reference formulation and two test combined AZT/3TC tablets, in an
      open, three-period, balanced, randomized, crossover protocol. Based on the 90%
      confidence interval of the individual ratios (test formulation/reference
      formulation) for C(max) (peak serum concentration) and AUC(0-inf) (extrapolated
      area under the serum concentration vs. time curve from time zero to infinity), it
      was concluded that the two test formulations are bioequivalent to the reference
      formulation with respect to the rate and extent of absorption of both 3TC and
      AZT.

PMID- 15150841
TI  - Improved sensitivity for insulin in matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry by premixing alpha-cyano-4-hydroxycinnamic acid
      matrix with transferrin.
AB  - This report describes an enhancement of the signal intensities of proteins and
      peptides in matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS). When alpha-cyano-4-hydroxycinnamic acid (CHCA)
      premixed with human transferrin (Tf) was used as a matrix, the signal intensity
      of insulin was amplified to more than ten times that of the respective control in
      CHCA without Tf. The detection limit of insulin was 0.39 fmol on-probe in the
      presence of Tf, while it was 6.3 fmol in the absence of Tf. The signal intensity
      of insulin was also enhanced when the CHCA matrix was premixed with proteins
      other than Tf (80 kDa), such as horse ferritin (20 kDa), bovine serum albumin
      (BSA, 66 kDa), or human immunoglobulin G (150 kDa). The optimum spectrum of
      insulin was obtained when the added amount of protein was in the range 0.26-0.62
      pmol, regardless of the molecular weight of the added protein. Tf and BSA
      outperformed the other tested proteins, as determined by improvements in the
      resulting spectra. When the mass spectra of several peptides and proteins were
      recorded in the presence of Tf or BSA, the signal intensities of large peptides
      such as glucagon were enhanced, though those of smaller peptides were not
      enhanced. In addition, the signal enhancement achieved with Tf and BSA was more
      pronounced for the proteins, including cytochrome C, than for the large peptides.
      This enhancement effect could be applied to improve the sensitivity of MALDI
      TOFMS to large peptides and proteins.

PMID- 15150842
TI  - Simple fabrication of a structured matrix-assisted laser desorption/ionization
      target coating for increased sensitivity in mass spectrometric analysis of
      membrane proteins.
AB  - A new prestructured target plate for matrix-assisted laser desorption/ionization
      (MALDI) was developed specifically for hydrophobic integral membrane proteins.
      This sample support contains predefined concentrating sample spots with a
      focusing effect on droplets with a high content of hexafluoroisopropanol (HFIP).
      This fluorinated organic solvent is advantageous for solubilizing hydrophobic
      proteins that are not soluble in water or the organic solvents normally used in
      sample preparation protocols for MALDI-MS. The prestructured plate was
      constructed by coating a regular steel plate with a thin layer of a silicone
      polymer, leaving sample spots of bare steel. Fabrication of the concentrating
      silicone structure was fast and very straightforward, without expensive or
      complicated equipment. Removing the layer, and thus regenerating the steel plate,
      was done by a simple washing procedure. The application and cleaning procedure
      are not constrained by a particular design of sample support or to any specific
      brand of mass spectrometer. When using the prestructured MALDI plate with HFIP as
      the sample solvent for 17 pmol of a cyanogen bromide digest of the highly
      hydrophobic membrane protein bacteriorhodopsin, an improved focusing effect and
      an increase of more than five-fold in average sensitivity were observed, compared
      with a regular steel target. Experimental results show a two-fold increase in
      average sensitivity when the new prestructured target plate was used, compared
      with a commercially available concentrating support.

PMID- 15150843
TI  - Quantification of cow milk adulteration in goat milk using high-performance
      liquid chromatography with electrospray ionization mass spectrometry.
AB  - A method was developed for the quantification of cow milk adulteration in goat
      milk, based on solvent separation of whey proteins followed by high-performance
      liquid chromatography with electrospray ionization mass spectrometry (HPLC/ESI
      MS). The presence of cow milk was determined using beta-lactoglobulin whey
      protein as the molecular marker. The adulterants were identified using both
      retention time and molecular mass derived from multiply charged molecular ions.
      Standard solutions containing cow and goat milk in different volume ratios were
      prepared and analyzed. Good linearity covering cow milk content from 5% and above
      was obtained. The proposed method identifies the adulterants using accurate
      molecular masses for protein identification and detects the addition of cow milk
      to goat milk at levels as low as 5%.

PMID- 15150844
TI  - Structural characterization of aminoethylphenyl oligoglycosides in Schnabelia
      tetradonta.

PMID- 15150845
TI  - A modified nanospray tip coupled to a mass spectrometer for analyzing enzymatic
      peptides.

PMID- 15150846
TI  - Thinking, recognition, and otherness.

PMID- 15150847
TI  - Mirroring from the perspective of the theories of Matte-Blanco.

PMID- 15150848
TI  - The Interpretation of Dreams as part of Freud's psychobiography.

PMID- 15150849
TI  - Bruno Bettelheim as an anti-authoritarian teacher in Germany: reminiscences of
      the 1950s.

PMID- 15150850
TI  - Erich Fromm and postmodernism.

PMID- 15150851
TI  - Erich Fromm and contemporary psychoanalysis: from modernism to postmodernism.

PMID- 15150852
TI  - Janus-faced resilience in the analysis of a severely traumatized patient.

PMID- 15150853
TI  - Disability surveillance.

PMID- 15150854
TI  - Work organization interventions.

PMID- 15150855
TI  - Work organization interventions: state of knowledge and future directions.
AB  - Changes taking place in the modern workplace, such as more flexible and lean
      production technologies, flatter management structures, and nontraditional
      employment practices fundamentally alter work organization factors and raise
      concerns about potentially negative influences on worker health and safety. These
      changes raise concerns about adverse effects on worker safety and health and call
      attention to the need for interventions to counter these effects. This forum
      article provides an overview of work organization intervention research,
      highlights gaps in the research literature, and sets forth an agenda for future
      intervention research. Research to date has focused primarily on individual-level
      interventions, with far less attention to interventions at the legislative/policy
      level, employer/organization level, and job/task level. Future research is
      recommended to establish the effectiveness of work organization interventions
      using improved methodological designs and giving increased attention to the
      circumstances within organizations that promote the adoption of such
      interventions.

PMID- 15150856
TI  - The "black hole" of work organization interventions.

PMID- 15150858
TI  - Making workplaces healthier: generating better evidence on work organization
      intervention research.

PMID- 15150857
TI  - Health related interventions in organizations: stages, levels, criteria, and
      methodology.

PMID- 15150859
TI  - Work organization interventions in small and medium-sized enterprises in
      Scandinavia.

PMID- 15150860
TI  - Evolution of epidemiologic methods and concepts in selected textbooks of the 20th
      century.
AB  - Textbooks are an expression of the state of development of a discipline at a
      given moment in time. By reviewing eight epidemiology textbooks published over
      the course of a century, we have attempted to trace the evolution of five
      epidemiologic concepts and methods: study design (cohort studies and case-control
      studies), confounding, bias, interaction and causal inference. Overall, these
      eight textbooks can be grouped into three generations. Greenwood (1935) and Hill
      (first edition 1937; version reviewed 1961)'s textbooks belong to the first
      generation, "early epidemiology", which comprise early definitions of bias and
      confounding. The second generation, "classic epidemiology", represented by the
      textbooks of Morris (first edition 1957; version reviewed 1964), MacMahon & Pugh
      (first edition 1960; version reviewed 1970), Susser (1973), and Lilienfeld &
      Lilienfeld (first edition 1976; version reviewed 1980), clarifies the properties
      of cohort and case-control study designs and the theory of disease causation.
      Miettinen (1985) and Rothman (1986)'s textbooks belong to a third generation,
      "modern epidemiology", presenting an integrated perspective on study designs and
      their measures of outcome, as well as distinguishing and formalizing the concepts
      of confounding and interaction. Our review demonstrates that epidemiology, as a
      scientific discipline, is in constant evolution and transformation. It is likely
      that new methodological tools, able to assess the complexity of the causes of
      human health, will be proposed in future generations of textbooks.

PMID- 15150861
TI  - Interaction and evolution in epidemiology.

PMID- 15150862
TI  - Lack of evolution of epidemiologic "methods and concepts".

PMID- 15150863
TI  - Severity, timing, and structure of disability.
AB  - OBJECTIVES: Severity and timing are key aspects of disability experience for
      individuals. They also generate a population's disability structure (prevalence,
      counts, patterns). We study links among severity, duration, and structure for
      community-dwelling adults in the US. METHODS: The data source is the National
      Health Interview Survey Disability Supplement. Disabilities in personal care
      (ADL), household management (IADL), and physical functions (PLIM) are analyzed.
      RESULTS: Many combinations of disabilities are possible, but just a few are
      frequent; the top-10 patterns cover 70% of ADL, 89% of IADL, and 47% of PLIM
      disabled adults. Hierarchical patterns are common for ADLs and IADLs. People with
      many disabilities also have more-severe ones, and their disabilities often
      started at the same time. CONCLUSIONS: Disability structure reflects severity and
      timing of specific disabilities, sometimes strongly, and other times weakly due
      to exit processes from the community. Assumptions that disability occurs in
      "hard" tasks first and "easy" ones last, and that hard-and-early connotes mild
      disability whereas easy-and-late connotes severe, need direct empirical testing.

PMID- 15150864
TI  - Workplace characteristics and work disability onset for men and women.
AB  - OBJECTIVES: This paper investigates the association between job characteristics
      and work disability among men and women in older working ages in the United
      States. We examine whether the association persists when controlling for major
      chronic disease experience. We also address whether job characteristics are
      ultimately associated with the receipt of disability benefits. METHODS: Data are
      from the Health and Retirement Survey and are nationally representative of
      noninstitutionalized persons 51-61 in 1992. Disability onset is estimated using a
      hazard modeling approach for those working at wave 1 (N = 5,999). A logistic
      regression analysis of disability benefits is based on a risk set of 525 persons
      who become work-disabled before the second interview. RESULTS: Women's disability
      onset and health problems appear less related to job characteristics than men's.
      For men, work disability is associated with stressful jobs, lack of job control,
      and environmentally hazardous conditions but is not associated with physical
      demands. Participation in disability benefit programs among those with work
      disability is unrelated to most job characteristics or health conditions.
      CONCLUSIONS: Understanding of the differing process to work disability for men
      and women and the relationship between work and health by gender is important for
      current policy development.

PMID- 15150865
TI  - Age-related health risk behaviors of adolescents with physical disabilities.
AB  - OBJECTIVE: To investigate age-related differences in health risk behaviors in 11
      12-, 13-14-, and 15-16-year-old adolescents with physical disabilities. METHOD:
      Health survey data from 319 adolescents with physical disabilities were compared
      with the same data from 7,020 adolescents in a national sample. RESULTS:
      Significant age-related differences were found for having tried smoking, smoking,
      having tasted an alcoholic drink, having been drunk, and using prescription drugs
      for recreational purposes. However, changes were modest and engagement of 15-16
      year-old adolescents with physical disabilities was similar to 11-12-year-olds in
      the general population. Analysis of associations between disability status and
      health risk behaviors while controlling for age and sex showed that disability is
      associated with a lower likelihood of having tried smoking, smoking, having
      tasted an alcoholic drink, drinking, having been drunk, having used drugs, having
      used prescription drugs for recreational purposes, and eating sweets; a higher
      likelihood of not engaging in physical exercise, not eating fresh produce, and
      eating high-fat foods; and non-significant for seat-belt use. CONCLUSION: Health
      promotion programs about health risk behaviours designed for adolescents in the
      general population may not be appropriate for adolescents with physical
      disabilities.

PMID- 15150867
TI  - [An activating state and active citizen groups in the German health care system].
AB  - This paper discusses the question, to what extent concepts of an enabling state
      are realised in the German health policy and wether they meet active citizens
      with corresponding competencies. The analysis is based on a review of the
      literature referring to the promotion and development of the self-help movement
      and citizen participation in the German health care system. The results show,
      that since 1999 the following enabling health policy measures were adopted: the
      promotion of independent patient advisory services and shared decision-making,
      the enactment of participation rules in the rehabilitation system and the
      compulsory subsidy for self-help groups, self-help organisations and clearing
      houses for self-help. The active engagement of the citizens both as co-producers
      of health on the individual level and as participants in processes of
      communication and decision-making on the system level is still restricted to a
      small part of the population. An enabling health policy and a broad citizen
      participation are still in the beginning, but they have the potential to
      strengthen each other and to realise synergetic effects. Even though some
      corresponding institutions were already established and attitudes of the health
      care professionals start to alter, the question wether the health policy will
      change from a welfare producing state to an enabling state cannot be answered
      completely yet.

PMID- 15150868
TI  - The classification of health problems in health interview surveys: using the
      International Classification of Primary Care (ICPC).

PMID- 15150866
TI  - Disability trends in gender and race groups of early retirement ages in the USA.
AB  - OBJECTIVES: To analyse disability trends over the 1980s-1990s in gender and race
      groups of early retirement ages in USA. METHODS: Disability trends for white and
      black males and females aged 65-69 and 70+ are analysed using the 1982-1999
      NLTCS. Disability is analysed at three levels (instrumental activities of daily
      living (IADL), activities of daily living (ADL), and institutionalisation).
      RESULTS: 1) A larger increase in proportions of non-disabled blacks aged 65-69
      compared with whites and males compared with females. 2) Differences in
      disability trends among gender and race groups. 3) A faster absolute decline in
      non-institutionalised disabled aged 65-69. 4) A larger absolute decline and a
      smaller relative decline in proportions of disabled aged 70+ compared with 65-69.
      5) A significant decrease in the proportion of ADL disabled blacks and an
      increase of ADL disabled white females in the age group 70+. CONCLUSIONS:
      Americans aged 65-69 years manifest a significant improvement in health over the
      1980s-1990s but the dynamics differs in gender and race groups. Possible reasons
      for these differences are discussed.

PMID- 15150869
TI  - [An immunohistochemical study on the expression of caspase-3 in the skin wound
      healing].
AB  - OBJECTIVE: To investigate the expression of caspase-3 during skin wound healing
      and explore the applicability of caspase-3 to determination of wound age.
      METHODS: The expression of caspase-3 were performed on 33 mice skin incised
      wounds at different posttraumatic intervals and 3 mice as control by
      immunohistochemical technique. RESULTS: Expression of caspase-3 was detectable in
      polymorphonuclear cells (PMNs) in the wound specimens aged 6 h. In the wound
      specimens aged from 12 h to 24 h after injury, caspase-3 was identified in a
      large number of infiltrating PMNs and part of mononuclear cells (MNCs).
      Afterwards, the MNCs and fibroblastic cells (FBCs) accounted in the most part of
      the caspase-3 positive cells. Morphometrically, the ratio of the number of the
      caspase-3 stained PMNs, MNCs and FBCs to total number of the cells in the wounds
      was evaluated and calculated. The ratio of the caspase-3 positive cells was low
      in the wound specimens aged from 0 h to 3 h (4.53 +/- 6.53)%, and maximized in
      the wound specimens aged 3 day (62.66 +/- 4.84)%. Thereafter, the ratio decreased
      and minimized in the specimens aged 14 day (21.56 +/- 4.54)%. CONCLUSION: The
      results suggest that caspase-3 may play an important role in inducing neutrophil,
      macrophage and fibroblast apoptosis during skin wound healing. Furthermore,
      caspase-3 may be used as a marker for the wound age determination.

PMID- 15150871
TI  - [Correlation study between the connexin43 and the myocardial ischemia in rabbit].
AB  - OBJECTIVE: To study the correlation between quantity of the connexin43 express
      and ischemia time in rabbit. METHODS: Left coronary arteries were ligated to
      create early myocardial ischemia during distinct time, HBFP staining was used in
      the ischemia spot and SP method was used to show the expression of connexin43 and
      the ischemia are were measured by the computer image analysis. RESULTS: Negative
      correlation was observed between the connexin43 quantity and the ischemia time.
      The significant was difference. CONCLUSION: With ischemia time raised, expression
      of connexin43 was descented.

PMID- 15150870
TI  - [The dynamically changes of COX-2 and the gene expression of COX-2 mRNA after
      traumatic brain injury in rats].
AB  - OBJECTIVE: To illuminate the pathology of traumatic brain injury(TBI) and to
      better understand the relationship between the expression of COX-2 and the time
      course of TBI. METHODS: Immunocytochemical staining, double-labeled with the anti
      COX-2 antibody and either the neuron-specific antibody NeuN or the astroglial
      specific marker GFAP, in situ hybridization and computer image analysis were
      used. RESULTS: Results from immunohistochemistry indicated time-dependent
      staining changes of neuronal plasma. The immunostained cells were faint at
      control cortex, mostly were neurons. The immunostained cells appeared to be
      darkly stained 30 min after TBI for extended periods of time and reached the
      maximum at 2 d after injury, reached another peak (P < 0.05) at 4 d post-injury.
      The darker cells persisted in a high level, significant differences (P < 0.05)
      even presented between control and 15 d post-injury. The COX-2 mRNA expression
      was faint at control cortex. The expressions of COX-2 mRNA appeared to be darkly
      stained 15 min after TBI for extended periods of time and reached the maximum (P
      < 0.05) at 1 d post-injury, reached another peak (P < 0.05) at 3 d post-injury,
      and significant differences (P < 0.05) even presented between control and 7 d
      post-injury, but not 15 d post-injury. CONCLUSION: The results of this study
      indicated that the expression of COX-2 mRNA and protein had a possible
      relationship with the extended periods of time after TBI. It might have some
      relationship between the expression of COX-2 and secondary brain injury after
      TBI.

PMID- 15150872
TI  - [The study on the expression of caspase-3 in experimental brain contusion in
      rats].
AB  - OBJECTIVE: To investigate the expression of caspase-3 in different posttraumatic
      intervals and severity of brain injury. METHODS: The study examined brain tissue
      samples of slight (n = 24), severe (n = 24) brain injury and control (n = 6) of
      rat, using immunohistochemical staining, western-blot and RT-PCR method. RESULTS:
      Up-regulating of caspase-3 expression was found in tissue from traumatic brain
      injury compared with controls in early 1 hour after TBI, and lasted for 14 days.
      The gray degree and threshold area of caspase-3 positive cells is different in
      different severity of brain injury. CONCLUSION: The increasing of caspase-3
      expression indicates that TBI exists. The gray degree, threshold area of caspase
      3 positive cells and the cleavage degree of pro-caspase-3 have association with
      the severity of brain injury.

PMID- 15150873
TI  - [Expression of water channel protein 1 in the lung of the drown rat].
AB  - OBJECTIVE: To determine the expression of water channel 1 protein in the lung of
      drown rat and that of after death thrown into the water. METHODS:
      Immunohistochemical method was used and the computer image analysis was conducted
      to detect the distribution of AQP1. RESULTS: The positive expression of AQP1 was
      seen in the capillary endotheliocyte of the interstitial and around bronchi and
      in the alveolar endothelial cells. The value of intergrated optical density was
      statistical significant. CONCLUSION: It suggests that AQP1 is one of sensitive
      signs to distinguish ante-mortem and postmortem immersion.

PMID- 15150875
TI  - [Inferior orbital fissure and groove: axial CT findings and their anatomic
      variation].
AB  - OBJECTIVE: To show imaging findings of inferior orbital fissure (IOF) and groove
      (IOG) on axial CT scans and to discover their anatomic variations, so as to avoid
      misdiagnosing them as orbital fracture. METHODS: 25 normal skull were used to
      investigate the configurations of IOF and IOG. Five skulls were performed axial
      CT scans. 20 normal orbital axial scans were studied as well. MPR and RT-3D
      reconstructions were used in this study. RESULTS: Skulls scans and normal orbital
      images on axial CT showed three sorts of findings: (1) single bony dehiscence
      between lateral and inferior walls; (2) first type of double bony dehiscence
      between lateral and inferior walls, among the dehiscence interposing a small
      bone. The long axis of the small bone was parallel to orbital wall; (3) second
      type of double bony dehiscence between lateral and inferior walls, but the long
      axis of the small bone was in anteroposterior direction. Anatomy and variation of
      three sorts of CT findings were corresponded respectively to: (1) a baseball club
      shaped IOF; (2) a "V"-shaped IOF, that is composed of both of lateral and
      internal ramus, lateral ramus situates between the zygoma and the lateral portion
      of greater wing of sphenoid, and internal ramus between the maxilla and the
      internal portion of greater wing of sphenoid, both rami intercross caudally and
      open upwards in a "V"-shaped configuration; (3) a deep IOG with a protuberant
      lateral wall. CONCLUSION: Familiarity of imaging features on the axial CT scans
      and understanding of their anatomy of IOF and IOG would be helpful for avoiding
      misdiagnosis of orbital fracture.

PMID- 15150874
TI  - [Immunohistochemical observation of heart-type fatty acid binding-protein in
      early myocardial ischemia].
AB  - OBJECTIVE: The sensitivity of heart-type fatty acid binding-protein (H-FABP) in
      the postmortem diagnosis of myocardial ischemia was explored. METHODS: The
      changes of H-FABP staining in normal, infarcted and suspected ischemia of
      myocardial cells were studied by immunohistochemistry. RESULTS: There was no
      depletion in normal control group, and obvious depletion was observed in
      myocardial infarcted group. Among 9 suspected myocardial ischemia group, 3 cases
      showed obvious depletion and 3 cases showed vague depletion for H-FABP, there
      were obvious depletion of Mb in 4 suspected myocardial ischemia cases and vague
      depletion in 2 cases for Mb. It is indicated that H-FABP can be used to diagnose
      early myocardial ischemia. CONCLUSION: H-FABP is quite sensitive and useful for
      the diagnosis of early myocardial ischemia.

PMID- 15150876
TI  - [A population study of three Y-STR loci by multiplexing in Han population in
      Chengdu, China].
AB  - OBJECTIVE: To establish a better method determining three Y-STR loci. METHODS: A
      multiplex of Y-STRs and amplify simultaneously three Y-STRs loci. RESULTS:
      Establish successfully a multiplexing system of three Y-STR loci (DYS390, DYS391
      and DYS393) followed by a population genetic study of Han population in Chengdu,
      China. CONCLUSION: The diversity of haplotype is 0.8965, the value of
      discrimination and the chance of exclusion chance is 0.8965 with the standard
      error 0.0081. This established system is one of the good tools in personnel
      identification and genetic study.

PMID- 15150877
TI  - [A study on the effect of methanal during determination of carbon monoxide in
      blood].
AB  - OBJECTIVE: To confirm whether formaldehyde disturb detecting carbon monoxide in
      blood. To give an evidence that can be used for detecting carboxyhemoglobin more
      accurately in carbon monoxide posioning appraises. METHODS: Blood samples came
      from carbon monoxide poisoning and the health were collected. Regular methods for
      detecting carboxyhemoglobin were used. Observing and comparing the detection
      results between which were spiked with methanal and no spiked one were performed.
      RESULTS: Methanal will affect the result of following experiments such as
      heating, adding NaOH, absorbed by PdCl2 and spectrophotometry. CONCLUSION: The
      samples which contaminated by formaldehyde couldn't be used for detecting
      carboxyhemoglobin.

PMID- 15150879
TI  - [The study of status and advances on tetramine poisoning].
AB  - Tetramethylenedisulphotetramine(TETS) is virulent rodenticides which was strictly
      forbidden to use in China. Poison dose of TETS is very little, LD50 in rats in
      0.1 mg/kg. Manifestations and signs of TETS poisoning are showed in 5 min. The
      long dated effect of poisoning is extremely strict. Mamy studys on TETS are
      restricted on the treatment of TETS poisoning, while that of poisoning mechanism
      is very few. This paper reviewed TETS poisoning mechanism, pathological changes
      and research advances.

PMID- 15150878
TI  - [Arrhythmogenic right ventricular cardiomyopathy].
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease
      of unknown etiology characterized by fatty or fibrofatty infiltration of the
      right ventricular myocardium. It is well known that ARVC is one of the important
      causes of sudden death in young individuals. The significant pathological change
      of ARVC is atrophy and fibrofatty myocardial replacement of the right ventricular
      free wall. According to the histopathological substrate ARVC could be divided
      into 2 types: fatty and fibrofatty myocardial replacement. Possible etiology
      including: (1) apoptosis or programmed cell death; (2) inflammatory; (3)
      myocardium dysplasia and (4) myocyte transdifferentiation theory.

PMID- 15150880
TI  - [MVR-PCR and forensic medicine].
AB  - MVR mapping is one kind of DNA analytic techniques, which has developed greatly
      within 13 years. The molecular basis, history and applications in forensic
      medicine were systemically reviewed in this paper. Because of its umsubstitutive
      mole in forensic paternity test and individual identification, the technique is
      becoming one of the important methods of bioassay.

PMID- 15150881
TI  - Setting the compass for Texas dentistry for the 21st century.

PMID- 15150883
TI  - Gold Medal for Distinguished Service. Dr. John Duncan Wilbanks, El Paso (1997).

PMID- 15150882
TI  - Ethics redux.

PMID- 15150884
TI  - Gold Medal for Distinguished Service. Dr. Michael Don Vaclav, Amarillo (1998).

PMID- 15150885
TI  - Gold Medal for Distinguished Service. Dr. O.V. Cartwright, Cedar Hill (1999).

PMID- 15150886
TI  - Gold Medal for Distinguished Service. Dr. Henry Milton "Mit" Sorrels, Houston
      (2000).

PMID- 15150887
TI  - Gold Medal for Distinguished Service. Dr. Jack Harvey Harris, Pearland (1999).

PMID- 15150888
TI  - Gold Medal for Distinguished Service. Dr. James E. Bauerle, San Antonio (2002).

PMID- 15150889
TI  - Gold Medal for Distinguished Service. Dr. Robert V. Walker, Dallas (2003).

PMID- 15150890
TI  - The "dual degree". Does it change the scope of practice for oral and
      maxillofacial surgery?
AB  - The scope of practice for OMS is not, nor should it ever be, an issue of single
      or dual degree but must be related to the surgeon being trained to competence in
      the procedures performed. Future evolution will be based on continual
      advancements in the specialty and related areas as well as the development of new
      techniques. While the medical education may improve a core fund of general
      knowledge, the surgical residency and/or fellowship is the determinant of
      surgical competence and scope of practice.

PMID- 15150891
TI  - Ethical dilemma #47. "Friend or patient ... or both?".

PMID- 15150892
TI  - Dependability.

PMID- 15150893
TI  - Oral and maxillofacial pathology case of the month. Granular leukoplakia.

PMID- 15150894
TI  - Impaired endothelial responses in patients with deep hypothermic cardiopulmonary
      bypass.
AB  - We examined whether vascular endothelial function is impaired with deep
      hypothermia during cardiopulmonary bypass. Such impairment may cause the
      prolonged hypoperfusion of tissues or organs. Thirty adult patients were
      classified into three groups according to the degree of hypothermia during
      cardiopulmonary bypass; deep (DH: 18-20 degrees C, n = 10), moderate (MDH: 25-30
      degrees C, n = 10) and mild (MLH: 32-34 degrees C, n = 10) hypothermia. A bolus
      dose of 100 mg acetylcholine was injected, followed by 1 mg nitroglycerine 20 min
      later under hypothermic cardiopulmonary bypass. Plasma concentrations of nitric
      oxide metabolites (NOx) and endothelin-1 were determined until the 7th post
      operative day (POD). The reduction of arterial pressure after acetylcholine was
      the smallest in the DH group (-9 +/- 6 mmHg, p < 0.01). The time to reach the
      maximum reduction of arterial pressure was the longest in the DH group
      (acetylcholine: 47.7 +/- 23.6 sec, nitroglycerine: 53.4 +/- 21.4 sec, p < 0.01).
      NOx production was reduced until the 1st POD and then recovered. The recovery was
      more rapid in the MLH group than the other two groups (p < 0.01). The plasma
      endothelin-1 did not differ among the three groups. These results suggest that
      endothelial function is impaired during cardiopulmonary bypass with deep
      hypothermia.

PMID- 15150895
TI  - Extended indication criteria for endoscopic mucosal resection of early gastric
      cancer with special reference to lymph node metastasis--examination by
      multivariate analysis.
AB  - The purpose of this study was to clarify extended indication criteria of
      endoscopic mucosal resection (EMR) for early gastric cancer (EGC) by analyzing
      the independent risk factors involved in lymph node metastasis (LNM). Subjects
      were 422 patients who underwent gastrectomy with lymph node dissection for EGC at
      the Kurume University Hospital from 1994 to 2001. The EGCs were mucosal cancers
      (M) in 252 cases and submucosal cancers (SM) in 170 cases. Twelve clinico
      pathological factors were assessed for their possible association with LNM. On
      univariate analysis, EGC with LNM showed the following characteristics: size; 3.1
      cm or more, ulceration; present, heterogeneity; present, differentiation; poor,
      lymphatic vascular invasion; present, and invasion depth; SM2 (cancer penetration
      of submucosal layer, 0.5 mm or more from the muscularis mucosa). On multivariate
      analysis, the following four factors were identified as independent risk factors;
      invasion depth: Odds Ratio (OR) 10.9, lymphatic vascular invasion: OR 10.6, size:
      OR 3.2, and ulceration: OR 3.2. The incidence of LNM was 0% (0/141) (95%
      confidence interval, 0-2.6%) when these risk factors met the following four
      conditions: invasion depth; M or SM1 (cancer penetration of submucosal layer,
      less than 0.5 mm), lymphatic vascular invasion; absent, size; 3.0 cm or less, and
      ulceration; absent. It is concluded that EMR is a suitable radical treatment for
      EGC, and that the indication criteria for EMR can be extended depending on the
      results of the histological evaluation of the en bloc/total resected specimen
      concerning the above four factors for LNM.

PMID- 15150896
TI  - The consequences of cerebral venous circulatory disturbances associated with
      brain ischemia.
AB  - The aim of this study was to test the effects of interference with venous return
      from the brain on the brain damage produced by occlusion of the middle cerebral
      artery (MCA-O). Tests were performed in anesthetized, artificially ventilated
      rats. The extent of the infarction produced in the hemisphere ipsilateral to the
      occluded middle cerebral artery (MCA) was less in rats in which cerebral venous
      return had been disrupted by bilateral ligation of the external and internal
      jugular veins. The blood flow of a sample cortical area ipsilateral to the MCA-O
      (measure by a laser Doppler flowmeter) decreased less, during a 45 min MCA-O, in
      the group with venous return interference. The blood concentration of the marker
      of CNS damage (the S-100 protein), measured 24 hrs after the end of the 45 min
      MCA-O, was lower in the rats with venous return interference. In order to be
      effective, the interference with venous return had to start before, and be
      concurrent with, MCA-O. When the interference with venous return started during
      the period of MCA-O, the brain damage was enhanced and resulted in death of the
      animals within 24 hrs post-occlusion. It is concluded that increasing brain
      venous pressure may, under some conditions, protect brain tissue against ischemic
      damage.

PMID- 15150897
TI  - In vitro chemosensitivity of hepatocellular carcinoma for hepatic arterial
      infusion chemotherapy using the MTT assay with the combinations of antitumor
      drugs.
AB  - Despite the hepatic arterial infusion chemotherapy (HAI) has been advocated as an
      effective therapy for hepatocellular carcinoma (HCC) with multiple intrahepatic
      metastases, chemosensitivity of HCC for HAI with multidrug regimen has not been
      sufficiently investigated. The purpose of this study was to evaluate the in vitro
      chemosensitivity of HCC using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H
      tetrazolium bromide (MTT) assay with the combinations of various antitumor drugs,
      and compared with the clinical results of HAI for patients with multiple
      intrahepatic recurrences of HCC. To evaluate the in vitro chemosensitivity of HCC
      to the combinations of antitumor drugs, 54 resected specimens of HCC were assayed
      using MTT assay with seven antitumor agents, 5-fluorouracil (5-FU), mitomycin C
      (MMC), adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), methotrexate (MTX)
      and CPT-11 (SN-38), exposed singly, or in combination. The data were compared
      with the clinical results of HAI for patients who manifested the multiple
      intrahepatic recurrence. In addition, the in vitro combined effect of CDDP and 5
      FU for human hepatocellular carcinoma cell, KYN-1 and KYN-2, was analysed
      quantitatively. Of 54 resected specimens, 40 specimens assayed successfully, and
      an increased in vitro chemosensitivity of HCC when treated with combinations of
      antitumor drugs was observed: single drug 12.2%, two drugs combined 50.9% and
      three drugs combined 67.0%. The results of in vitro assay were well correlated,
      85.7% in predicting accuracy, with the clinical results of 14 patients who
      underwent HAI for multiple recurrence of HCC, and also correlated with the
      experimental results of the combined use of CDDP and 5-FU in KYN-1 and KYN-2 in
      terms of pharmacokinetic reactions, i.e. synergism or antagonism. The MTT assay
      with the combinations of antitumor drugs represents an informative
      chemosensitivity test to HAI with multidrug regimen for recurrence of HCC.

PMID- 15150898
TI  - Segmental difference in epithelial and mucosal barrier functions between the
      jejunum and the ileum in cold storage small bowel grafts in the rat.
AB  - The purpose of this study was to determine the differences in epithelial and
      mucosal barrier function between the jejunum and the ileum at transplantation.
      Rat small bowel was preserved in cold University of Wisconsin solution for 0, 12
      or 24 hrs. Time-related segmental differences in the potential differences, at
      rest (rPD) and upon glucose stimulation (PDgs), and in the permeation rates of
      phenolsulfonphtalein (PSP) and polyethylene glycol 4000 (PEG) as non-absorbable
      markers were studied after a 20-min reoxygenation period following cold
      preservation. Time-related histologic damage during cold preservation was also
      evaluated. After 24 hrs of preservation, when the villi were denuded both in
      jejunum and ileum, the rPD (1.4 +/- 0.3 mV/cm2) and PDgs (1.4 +/- 0.3 mV/cm2) of
      the jejunum were significantly lower than those of the ileum (1.9 +/- 0.3 mV/cm2
      and 2.1 +/- 0.3 mV/cm2, respectively). A difference in PEG permeation rates
      occurred after 24 hrs of preservation. The permeation rate of PSP in the jejunum
      was 10.5 +/- 1.0%, which was significantly higher than that in the ileum (8.6 +/-
      1.0%) after 12 of preservation, when subepithelial edema occurred both in the
      jejunum and ileum. Our functional study demonstrated that, in the rat small
      bowel, the ileumis more resistant than the jejunum to cold preservation.

PMID- 15150899
TI  - Pathological proof of cellular death in radiofrequency ablation therapy and
      correlation with flash echo imaging--an experiment study.
AB  - The aims of this study were to clarify the geographic distribution of complete
      cell death in the radiofrequency ablated area in a porcine liver experiment, and
      to evaluate the efficacy of ultrasonography using contrast media in detecting the
      area of Radiofrequency-induced cell death. Radiofrequency ablation was performed
      at 3 sites in each liver in seven swine with a RF2000TM radiofrequency generator
      using an expandable type needle electrode. The ablation area was investigated
      histologically by Hematoxylin-Eosin staining and NADH staining. The area of
      radiofrequency-induced cell death was correlated to the ultrasonographic findings
      using contrast media, by means of contrast harmonic imaging, flash echo imaging
      subtraction and flash echo imaging-power Doppler. The ablation area showed three
      distinct regions. Although the HE staining did not indicate necrosis, the NADH
      staining showed a complete loss of cellular activity in the inner and middle
      layers of the ablation area. However, in the outer layer cells displaying
      cellular integrity were intermingled with the necrotic cells, indicating that
      some of the cells in this layer had a chance to survive. Further, in some cases
      the outer layer of the ablated area had irregular margins. The flash-echo power
      doppler images were accurately correlated in size and shape to the pathologically
      proved region of complete cell death in the radiofrequency-induced lesions. In
      the marginal part of the radiofrequency ablation area, cell death was incomplete.
      Flash echo imaging-power doppler was a useful and sensitive real time imaging
      technique for accurate evaluation of the region of complete cell death.

PMID- 15150900
TI  - Clinical features of acute respiratory infections associated with the
      Streptococcus milleri group in the elderly.
AB  - The Streptococcus milleri group are becoming increasingly recognized as important
      pulmonary pathogens which may lead to the development of empyema or lung
      abscesses. Although several small series have been reported, the clinical and
      laboratory features of Streptococcus milleri infection have yet to be fully
      characterized in the elderly. We retrospectively examined the clinical features
      of 19 patients with Streptococcus milleri pulmonary disease who were admitted to
      our hospital between 2000 and 2002, based on their clinical records and
      laboratory data. The microbiological diagnosis was based on the results of
      quantitative sputum culture and other invasive procedures, including
      transthoracic needle aspiration or bronchoscopic examinations. There were
      thirteen cases of pneumonia, two of contaminant pneumonia and pleuritis, one of
      bronchitis, two of pulmonary abscess, and one of empyema. The patients ranged in
      age from 65 to 91. The most common symptoms at presentation were shortness of
      breath, coughing, sputum, and weight loss. An underlying disease existed in 14 of
      the 19 cases. We conclude that the Streptococcus milleri group is a more
      important cause of pulmonary infections than has been previously recognized.

PMID- 15150901
TI  - Risk of death due to hepatocellular carcinoma among drinkers and ex-drinkers.
      Univariate analysis of JACC study data.
AB  - Hazard ratios (HR) of death due to hepatocellular carcinoma (HCC) were analyzed
      by gender and age strata (40-59 and 60-79) among drinkers and ex-drinkers in
      66,974 eligible subjects from a a large cohort of male and female subjects aged
      40-79 years, based on information about several drinking related characteristics.
      The HR of dying from HCC for ex-drinkers was 4 to 8 times higher than for those
      who had never consumed alcohol at the baseline survey. When the subjects were
      restricted to those without history of liver disease (LD), the HR was still high
      for ex-drinkers among younger males, though the difference was not statistically
      significant. It appeared that the earlier drinking habits were established, the
      higher the HR, especially for younger males without LD. Among total current
      drinkers, the amount ingested per occasion and the cumulative amount ingested at
      the baseline did not show significantly increased HRs. Among subjects without LD,
      larger amounts ingested per occasion and larger cumulative amount seemed to have
      higher HRs in older male current drinkers. Frequent drinking and later age (50 to
      79) at cessation of drinking were associated with higher HRs among both genders
      and both age strata. After restricting the analysis to subjects without LD, many
      of these increased HRs remained among males. The results suggested that the
      association between alcohol drinking history and HR of HCC differs depending on
      the presence of LD. Major confounders other than age and gender associated with
      both drinking and HCC, e.g. smoking, hepatitis virus infection, or history of
      diabetes, were not considered in this analysis, and the observed associations
      might be confounded by any of these factors. To clarify the net association
      between alcohol drinking and HCC, further analysis is needed to control potential
      confounders, including past history of liver disease, and to consider probable
      effect modifiers.

PMID- 15150902
TI  - Risk of death due to hepatocellular carcinoma among smokers and ex-smokers.
      Univariate analysis of JACC study data.
AB  - Hazard ratios (HR) of death due to hepatocellular carcinoma (HCC) were analyzed
      by gender and age strata (40-59 and 60-79) among smokers and ex-smokers in 65,528
      eligible subjects from a large cohort of males and females aged 40-79 years,
      based on information about several smoking-related characteristics. Both current
      smokers and ex-smokers among total older males had hazard ratios (HR) for dying
      from HCC that were 2 to 4 times higher than those who had never smoked at the
      baseline survey. When subjects were restricted to those without history of liver
      disease (LD), older male (60-79) ex-smokers presented a statistically significant
      HR of 5.0. Earlier age at start of smoking (15 to 19) showed a significantly
      increased HR of 4 to 8 for both current and ex-smokers. Moderate number of
      cigarettes smoked per day showed an increased HR, and later age at cessation of
      smoking had a higher HR compared to earlier cessation. Larger cumulative amount
      of smoking resulted in an elevated HR of 11 times than in those who had never
      smoked. Cigarette smoking was suggested to be an important risk factor for death
      from HCC regardless of whether the smoking habit was in the past or was
      continuing at present. To eliminate confounding effects and interaction with
      other risk factors of HCC and to clarify the net association between smoking
      habits and HCC, farther careful analysis using multivariate models is needed.

PMID- 15150903
TI  - Efficacy of n-3 polyunsaturated fatty acid enriched enteral nutrient solution in
      relieving oxidative stress in patients with severe psychophysiologic disorders.
AB  - It is not unusual for patients with severe motor and intellectual disabilities to
      present with eating and swallowing disorders, and such patients often require
      long term enteral nutrition. These patients tend to receive all their nutrients
      in the form of a single nutrient solution that is administered over a long
      period, and there are concerns about the impact of the composition of these
      nutrient formulas on patient health. Therefore, it is very important that
      adequate care be taken when selecting a nutrient formula for patients of this
      type. In the present study we administered two types of enteral nutrient
      solutions and examined the effect of the differences in nutrient composition on
      the degree of oxidative stress experienced by human patients. Subjects were 5
      patients (mean age: 27.2 years; male/female ratio: 4:1) with severe motor and
      intellectual disabilities who were incapable of oral feeding, and who were
      receiving long term enteral nutrition. The subjects were administered a standard
      elemental diet for 2 months, and this was followed by administration of an n-3
      polyunsaturated fatty acid enriched enteral nutrient solution for three months.
      Results showed that the n-3 polyunsaturated fatty acid enriched diet improved
      serum concentrations of trace elements, protein synthesis, and the balance
      between n-6 polyunsaturated fatty acids and n-3 polyunsaturated fatty acids,
      which are essential fatty acids. At the same time oxidative stress was reduced,
      and serum IgE levels declined significantly. Patients with severe
      psychophysiological disorders often suffer from repeated bouts of pneumonia due
      to immune system suppression, and there are reports that such patients are
      subject to increased allergic diathesis. The present results indicated that the
      in vivo membrane damage induced by oxidative stress may be closely related to the
      onset of these disorders. The results also suggested that in addition to
      attaining an adequate understanding of the effect of each of the various
      nutrients in enteral nutrient formulas, it will also be important to consider not
      only trace elements but also fatty acid composition in the nutritional management
      of patients with such disorders.

PMID- 15150905
TI  - A case of pulmonary embolism after abdominal angiography.
AB  - The patient was a 72-year-old woman who had been diagnosed with
      cholecystolithiasis and had undergone laparoscopic cholecystectomy. Since the
      postoperative pathologic diagnosis was a gallbladder cancer with a depth of wall
      penetration of subserosa, she was admitted to Kurume University Hospital for a
      second-look operation. After admission, abdominal angiography was performed with
      a right femoral arterial puncture. After the release of inguinal compression with
      a belt, chest pain and difficulty in breathing appeared. Despite her normal blood
      pressure, arterial blood gas analysis showed a PO2 of 74.7 mmHg and a PCO2 of
      41.5 mmHg, representing a slight decrease in PO2. Chest X-rays showed an
      increased cardiothoracic ratio and decreased lucency in the left upper lung
      field. The electrocardiogram revealed atrial premature contraction. Cardiac
      ultrasound did not show expansion of the right heart and blood vessels or
      abnormal structures in the main pulmonary artery. Since lung perfusion
      scintigraphy revealed perfusion defects in the left upper to middle and right
      upper lung fields, acute pulmonary embolism was diagnosed, and oxygen inhalation,
      thrombolytic, and anticoagulant therapy were instituted immediately. The symptoms
      improved the following day, but 240,000 u/day of urokinase was administered for 5
      days, and 1,500 u/day of heparin for 10 days. On lung perfusion scintigrams 6
      days later, the defects had disappeared. Moreover, no definite abnormal shadows
      were noted on chest X-rays. Radical surgery for gallbladder cancer was performed
      3 weeks later. Considering the possible development of pulmonary embolism, we
      felt the need for careful management if the patient is released from bed rest
      after abdominal angiography.

PMID- 15150904
TI  - Right atrial myxoma in a patient presenting with syncope.
AB  - We describe a case of right atrial myxoma in a 62-year-old woman presenting with
      syncope. The patient had a 4-month history of syncope and felt faint on lying
      flat in bed before the admission. Transthoracic and transesophageal
      echocardiography showed a large right atrial mass that was prolapsing through the
      tricuspid valve into the right ventricle during diastole. Coronary angiography
      revealed a tumor stain through the right coronary artery and no significant
      stenosis of the coronary arteries. During operation, cardiopulmonary bypass was
      initiated with cannulation into the aorta and retrograde femoral vein and
      superior vena caval cannulation. The large tumor was attached by a short stalk to
      the interatrial septum at the border of the fossa ovalis. The tumor and the
      interatrial septum including the stalk with a 1.5-2.0 cm cuff extending the full
      thickness of the septum were completely excised. A histologic examination of the
      tumor confirmed the diagnosis of cardiac myxoma. We emphasize a characteristic
      feature of syncopal attacks, and discuss the importance of prevention of
      intraoperative systemic and pulmonary tumor embolization resulting from venous
      cannulation for cardiopulmonary bypass in patients with right atrial myxomas.

PMID- 15150906
TI  - Nesidioblastosis treated successfully by 85% pancreatectomy.
AB  - Nesidioblastosis is a rare disorder in pediatric surgery. It is caused by
      hypertrophy and hyperplasia of the islands of Langerhans, and can lead to
      persistent hyperinsulinemic hypoglycemia. If appropriate treatment is delayed
      there is a high risk of the development of cerebral palsy, impaired mental
      development, epilepsy or other forms of irreversible brain damage, so early
      detection and early treatment to stabilize serum glucose levels is essential.
      Initial treatment consists of nutritional management with administration of an
      adequate amount of calories along with drug therapy using diazoxide. In cases
      that are resistant to drug therapy a subtotal pancreatectomy is performed.
      Conventional recommended practice has been to perform a 95% pancreatectomy,
      however this can lead to the onset of diabetes due to abnormal pancreatic
      endocrine function. We report here a case of nesidioblastosis in which we
      performed an 85% pancreatectomy. Postoperative clinical course has been
      excellent, with no recurrence or impaired glucose tolerance during the four years
      since the operation.

PMID- 15150908
TI  - NP insurance premiums are rising--how high is too high?

PMID- 15150909
TI  - Defining your mission and vision.

PMID- 15150910
TI  - A rare cause of rectal bleeding.

PMID- 15150911
TI  - Billing for student services.

PMID- 15150912
TI  - Crohn's disease. Achieving optimum health status.

PMID- 15150913
TI  - Patient information. Eggs: big nutrition in a small package.

PMID- 15150914
TI  - Recreation therapy for dementia-related behaviors. Guidelines for nurse
      practitioners.

PMID- 15150915
TI  - Is that all there is? Why more patients are seeking alternative therapies.

PMID- 15150916
TI  - Magnet therapy for pain control. An analysis of theory and research.

PMID- 15150917
TI  - Look younger, live longer. Can dietary supplements deliver on their promises?

PMID- 15150918
TI  - Empowering parents for SIDS prevention. Nurse practitioners play key role.

PMID- 15150919
TI  - Compliance with mammography screening. Identifying common barriers.

PMID- 15150920
TI  - Pass the word. Marketing campaign calls on NPs to act locally.

PMID- 15150921
TI  - West Nile virus in the United States. An update on incidence and research.

PMID- 15150922
TI  - Coming back for more.

PMID- 15150923
TI  - More on probiotics.

PMID- 15150924
TI  - More on probiotics.

PMID- 15150926
TI  - Fee for service.

PMID- 15150928
TI  - Top doctors want tougher perversity penalties.

PMID- 15150927
TI  - Jan Mikulicz-Radecki--father of surgical endoscopy.

PMID- 15150929
TI  - ANC comes out swinging on CON.

PMID- 15150930
TI  - Mpumalanga Health Department unravelling begins....

PMID- 15150931
TI  - Can early regional analgesia blocks benefit patients?

PMID- 15150933
TI  - Health professionals agree to become non-smoking role models.

PMID- 15150932
TI  - Polio--is this the last chance for eradication?

PMID- 15150934
TI  - Psychoneuroimmunology--mind-brain-immune interactions.

PMID- 15150935
TI  - The development of medical tariffs in South Africa.

PMID- 15150936
TI  - The treatment of alcohol dependence--new horizons.

PMID- 15150937
TI  - There are worse things to celebrate.

PMID- 15150938
TI  - Probiotics--how functional are they?

PMID- 15150939
TI  - Expanding access to antiretroviral therapy through the public sector--the
      challenge of retaining patients in long-term primary care.

PMID- 15150940
TI  - Unabated rise in number of adult deaths in South Africa.

PMID- 15150941
TI  - Immunogenicity and safety of yeast-derived recombinant hepatitis B vaccine
      (Heberbiovac HB) in South African children.

PMID- 15150942
TI  - Susceptibility of a series of routine sputum samples for antituberculosis
      chemotherapy in Gweru, Zimbabwe.

PMID- 15150943
TI  - South African national household survey of HIV/AIDS prevalence, behavioural risks
      and mass media impact--detailed methodology and response rate results.
AB  - OBJECTIVES: To describe the methodology used in a recent survey of HIV/AIDS in
      South Africa and to present the response rates. METHODS: A cross-sectional,
      national household-based survey was conducted using second-generation
      surveillance procedures. A complex multistage sampling technique was used to
      create a master sample of 1,000 census enumerator areas out of a total of 86,000
      nationally. Aerial photographs were taken and used to randomly select more than
      10,197 households and ultimately 13,518 individuals from a sampling frame of
      31,321 people. Phase 1 of the study involved notifying the household residents
      about the study and collecting key demographic information on respondents aged 2
      years and older. This information was used to randomly select up to 3 respondents
      from each household: 1 adult (25 years and older), 1 youth (15-24 years), and 1
      child (2-14 years). In phase 2 nurses interviewed respondents and collected oral
      fluid specimens for HIV testing. In the case of children aged 2-11 years, parents
      or guardians were interviewed, but HIV testing was performed on the selected
      children. Questionnaire data were anonymously linked with HIV test results.
      RESULTS: A total of 9,963 persons agreed to be interviewed and 8,840 were tested
      for HIV, yielding a response rate of 73.7% and 65.4% respectively. However, only
      8,428 (62.3%) HIV test results were correctly matched with behavioural data. The
      results showed that those tested for HIV did not differ from those not tested in
      terms of key determinants. CONCLUSION: It is possible to use community-based
      surveys to study the prevalence of HIV in the general population.

PMID- 15150944
TI  - PMTCT from research to reality--results from a routine service.
AB  - OBJECTIVES: Assessment of the efficacy of a prevention of mother-to-child
      transmission (PMTCT) programme in a routine service setting in comparison to a
      research environment. DESIGN: Descriptive study over a 13-month period utilising
      retrospective data obtained from hospital records complemented by prospective
      data on a sample of patients enrolled in a study to determine an affordable HIV
      diagnostic protocol for infants. SETTING: Routine PMTCT service at Coronation
      Women and Children's Hospital (CWCH) situated in Johannesburg and affiliated to
      the University of the Witwatersrand. SUBJECTS: Pregnant women known to be HIV
      infected who delivered at CWCH from 1 October 2001 to 31 October 2002. OUTCOME
      MEASURES: The HIV transmission rate to infants, which reflects nevirapine (NVP)
      delivery and infant feeding practices, and follow-up rates of perinatally exposed
      children. RESULTS: Of the 8,221 deliveries, 1,234 (15%) occurred in women known
      to be HIV infected. HIV transmission rates of 8.7% at 6 weeks and 8.9% at 3
      months of age in the study population verifies the high rate of NVP
      administration and the ability of women to formula-feed their babies and abstain
      from breast-feeding. More than one-third of infants never return for follow-up
      and more than 70% are lost to follow-up by 4 months of age. CONCLUSIONS: The low
      HIV transmission rate confirms the efficacy of this routine service PMTCT
      programme. HIV-infected children are not being identified for medical management
      as part of PMTCT follow-up. It is imperative that record keeping is improved to
      facilitate ongoing monitoring.

PMID- 15150945
TI  - Inhuman shields--children caught in the crossfire of domestic violence.
AB  - BACKGROUND: Child abuse is a worldwide scourge. One of its most devastating
      manifestations is non-accidental head injury (NAHI). METHODS: This is a
      retrospective chart review of children presenting to the Red Cross Children's
      Hospital trauma unit with a diagnosis of NAHI over a 3-year period. RESULTS:
      Sixty-eight children were included in the study and 2 different groups were
      identified. Fifty-three per cent of the children were deliberately injured
      (median age 2 years), while 47% were allegedly not the intended target of the
      assailant (median age 9 months). The assailant was male in 65% of the intentional
      assaults and male in 100% of the unintentional assaults, with the intended adult
      victim female in 85% of the latter cases. Overall, 85% of the assaults were
      committed in the child's own home. CONCLUSIONS: The high proportion of cases in
      which a young child was injured unintentionally suggests that these infants
      effectively become shields in assaults committed by adults. In this context any
      attempts to deal with child abuse must also address the concurrent intimate
      partner violence.

PMID- 15150946
TI  - Outcome of hospital-based TB in the Goldfields area.

PMID- 15150948
TI  - [Is the health of the elderly really worse nowadays?].

PMID- 15150947
TI  - Massive pulmonary haemorrhage as a cause of death in the neonate--a retrospective
      review.
AB  - OBJECTIVES: To examine massive pulmonary haemorrhage as an independent factor and
      as a co-factor in neonatal mortality by analysing the associated factors, with
      the purpose of identifying predisposing characteristics. DESIGN: A retrospective
      study reviewing 32 neonates who died of pulmonary haemorrhage. Data were
      extracted from the 2001 King Edward VIII Hospital (KEH) neonatal death records.
      Relevant obstetric and neonatal variables were used in the data analysis.
      SETTING: KEH, a tertiary care institute, provides secondary and tertiary services
      and functions as a referral centre for surrounding clinics and hospitals.
      RESULTS: Pulmonary haemorrhage occurred in 32 of 260 neonatal fatalities (12.3%).
      All cases of pulmonary haemorrhage fell into the low-birth-weight category (<
      2,500 g), and 26 of the infants (81.25%) died during the early neonatal period. A
      gestational age of 28-32 weeks was recorded in 27 cases (87%) and 19 (60%) showed
      adequate growth for gestational age. Three infants had pulmonary haemorrhage as a
      primary cause of death. In the remaining 29, pulmonary haemorrhage was secondary
      to a variety of causes. Obstetric information revealed that 29 mothers (93.5%)
      experienced obstetric complications, viz. pre-eclampsia/eclampsia syndrome 21
      (64.5%), abruptio placentae 5 (16.1%) and previous pregnancy losses 9 (29%).
      Seven babies were ventilated and 2 were diagnosed with patent ductus arteriosus.
      CONCLUSION: The study revealed more well-grown babies than expected.
      Complications of pregnancy hypertension, abruptio placentae and previous
      pregnancy losses were more frequently associated with pulmonary haemorrhage in
      these neonates. The majority of babies suffering pulmonary haemorrhage were not
      associated with intensive care management.

PMID- 15150949
TI  - [The Lakartidningen 100 years ago. "Day center" for poor people with TBC].

PMID- 15150951
TI  - [Health status of the oldest old has changed for the worse. Big differences
      between the sexes--health of the women is worse than health of the men as
      illuminated by new data].

PMID- 15150950
TI  - [Microbial diagnosis with PCR will become clinically beneficial with a faster
      analysis].
AB  - PCR was introduced in 1985 by Mullis and was immediately recognized as a valuable
      tool in biomedical research and was awarded the Nobel Prize in 1993. Two culture
      negative meningitis cases are described where Haemophilus influenzae and
      Neisseria meningitidis were found by 16SRNA-PCR. The modern real time PCR
      technology using fluorescent probes (hybridization probes, lightup probes,
      molecular beacons etc) for detection of the PCR-product or on DNA microarray
      chips, is under development for routine use. Multiplex technology can be used to
      simultaneously detect multiple microorganisms as well as resistance genes. Using
      super-convection with ultracentrifugation high-speed PCR, results can be obtained
      in 10 minutes and the amplificate can also be analyzed by DNA-sequencing to
      achieve species identification as well as detection of resistance gene mutations.
      The technique has mainly been applied to viruses, but is now slowly adapted to
      bacteria, fungi, protozoa and helminths. PCR is especially well suited for slow
      growing bacteria like Mycobacteria, fastidious organisms like Bartonella and
      contagious agents like tularemia, but also for malaria and fungi, where the
      advantages in sensitivity and speed can be exploited. The limit for application
      to routine analysis will depend on the development of simple and fast procedures
      for nucleic acid extraction, as well as interpretation of the PCR analysis per
      se, since highly efficient thermocyclers now are on the markets.

PMID- 15150952
TI  - [Sleep as recovery after stress].

PMID- 15150953
TI  - [Treatment of venous leg ulcers can be better and cheaper. Annual costs
      calculation based on an inquiry study].
AB  - Weekly resource use data for local wound treatment was collected from a clinical
      survey (138 patients). Annual costs were calculated from the weekly resource
      usage multiplied by unit costs and published epidemiological prevalence data for
      Sweden. The average weekly cost was 101 euro, though it differed depending by
      ulcer size. The total direct annual cost of venous leg ulcers in Sweden could be
      estimated at 73 million euro (2002 prices, 1 euro = SEK 9.16) based on a point
      prevalence of 0.3 percent and 45 percent venous ulcers. Treatment of leg ulcers
      seems to have improved compared with previous reports, resulting in slightly
      decreased costs. Nevertheless, the costs are still substantial and the management
      of these patients requires large resources. A more structured management, more
      careful selection of dressing products and decreased frequency of dressing
      changes imply further improvements in wound healing and quality of life for
      patients and decreased costs for the health care system and for society.

PMID- 15150954
TI  - [Prognosis in unstable coronary artery disease. Multimarker strategy is the best
      basis for the therapeutic choice].
AB  - Patients with unstable coronary artery disease have a serious but variable
      prognosis. An early and specific prediction of risk is essential for
      stratification of treatment. Serum was obtained at a median of 9.5 hours from
      symptom onset in 7800 patients with unstable coronary artery disease included in
      the GUSTO-IV trial for analyses of creatinine, troponin-T, C-reactive protein
      (CRP) and N-terminal pro brain natriuretic peptide (NT-proBNP). Quartiles of
      troponin-T were related to an increased mortality and to an increased incidence
      of myocardial infarction. Increasing quartiles of C-reactive protein were also
      related to an increased mortality but there was no relation to the incidence of
      myocardial infarction. On multivariate analysis, troponin-T was the strongest
      marker for prediction of myocardial infarction, but reduced creatinine clearance
      and ST-depression at admission were also significant predictors. Prediction of
      subsequent mortality was possible with several risk indicators. Elevation of NT
      proBNP was the strongest predictor of short and long-term mortality with a
      continuous increase in one-year mortality in relation to the levels. Also reduced
      creatinine clearance, elevation of CRP, troponin-T, ST-depression and clinical
      factors indicating a history of cardiovascular disease provided independent
      prognostic information on long-term mortality. A multimarker strategy with
      creatinine clearance, troponin, CRP and NT-proBNP together with ischemic ECG
      changes and clinical background characteristics provides the best prognostic
      information for choice of treatment in patients with unstable coronary artery
      disease.

PMID- 15150955
TI  - [The ancient roots of psychiatry. Ancient literature, philosophy and medicine put
      the basis of the current specialty].

PMID- 15150956
TI  - [The epoch-making invention--for the sake of vision. Eyeglasses used by people in
      Skane already 500 years ago].

PMID- 15150957
TI  - [A quack's confessions].

PMID- 15150958
TI  - [Perforated appendix was the beginning of the artistry of Henri Matisse].

PMID- 15150959
TI  - [Patients with heart failure should primarily be treated with ACE inhibitors].

PMID- 15150960
TI  - [New data on hypothermia in heart arrest--available treatment should be offered].

PMID- 15150961
TI  - [Remarkable assessment by the HSAN].

PMID- 15150962
TI  - [No information about interactions with nicotine in the Fass].

PMID- 15150963
TI  - [Warning for Ellen!].

PMID- 15150964
TI  - [The doctor in Enkoping "was so nice"].

PMID- 15150965
TI  - [Time to introduce a common emergency hotline?].

PMID- 15150967
TI  - [Neuroendocrine tests could prove somatization].

PMID- 15150969
TI  - [Functional organization of the brain during the operation of the working
      memory].

PMID- 15150970
TI  - [Influence of lateral masking on contrast detection thresholds of bars different
      in width].

PMID- 15150972
TI  - [Subjective acoustic field of patients with cortical temporal lobe epilepsy as
      revealed using signals simulating various directions of sound movement].

PMID- 15150971
TI  - [Influence of the emotional perception of a signal on the electroencephalographic
      correlates of the creative activity].

PMID- 15150973
TI  - [The influence of the white noise masking some temporal parameters of the
      auditory localization of radially moving targets].

PMID- 15150974
TI  - [A psychophysiological study of emotional disorders in patients during post
      stroke rehabilitation period].

PMID- 15150976
TI  - [Intra-systemic and inter-systemic rearrangements of the physiological parameters
      in experimental acute hypoxia].

PMID- 15150975
TI  - [The features of psychomotor responses and brain interhemispheric relationships
      at the stages of the adaptation to a new time zone].

PMID- 15150977
TI  - [Morphological and functional changes in overweight persons under combined
      normobaric hypoxia and physical training].

PMID- 15150978
TI  - [Pharmacological ethnic metabolic safety. Communication II].

PMID- 15150979
TI  - Multiple resonances among time structures, chronomes, around and in US. Is an
      about 1.3-year periodicity in solar wind built into the human cardiovascular
      chronome?
AB  - AIMS: Velocity changes in the solar wind, recorded by satellite (IMP8 and Wind)
      are characterized by a solar cycle dependent approximately 1.3-year component.
      The presence of any approximately 1.3-year component in human blood pressure (BP)
      and heart rate (HR) and in mortality from myocardial infarction (MI) is tested
      and its relative prominence compared to the 1.0-year variation. MATERIALS AND
      METHODS: Around the clock manual or automatic BP and HR measurements from four
      subjects recorded over 5 to 35 years and a 29-year record of mortality from MI in
      Minnesota were analyzed by linear-nonlinear rhythmometry. Point and 95%
      confidence interval (CI) estimates were obtained for the approximately 1.3-year
      period and amplitude. The latter is compared with the 1.0-year amplitude for BP
      and HR records concurrent to the solar data provided by one of us (JDR). RESULTS:
      An approximately 1.3-year component is resolved nonlinearly for MI, with a period
      of 1.23 (95% CI: 1.21; 1.26) year. This component was invariably validated with
      statistical significance for BP and HR by linear rhythmometry. Nonlinearly, the
      95% CI for the 1.3-year amplitude did not overlap zero in 11 of the 12 BP and HR
      series. Given the usually strong synchronizing role of light and temperature, it
      is surprising that 5 of the 12 cardiovascular series had a numerically larger
      amplitude of the 1.3-year versus the precise 1.0-year component. The beating of
      the approximately 1.3-year and 1.0-year components was shown by gliding spectra
      on actual and simulated data. DISCUSSION AND CONCLUSION: The shortest 5-year
      record (1998-2003) revealed an approximately 1.3-year component closer to the
      solar wind speed period characterizing the entire available record (1994-2003)
      than that for the concurrent 5-year span. Physiological variables may resonate
      with non-photic environmental cycles that may have entered the genetic code
      during evolution.

PMID- 15150981
TI  - [Changes in bioenergetic functions and performance capacity of athletes after
      administration of polyphenolic antihypoxic agents].

PMID- 15150980
TI  - [Age-related changes in contractile capacity of lower extremity muscle caused by
      inadequate blood supply].

PMID- 15150982
TI  - [Oxygenation of native and UV-modified human hemoglobin in the presence of nitric
      oxide].

PMID- 15150983
TI  - [Effect of the adsorbed proteins on the rheological properties of erythrocytes].

PMID- 15150984
TI  - [Parameters of the body's provision with riboflavin and the glutathione reductase
      activity in residents of the European North of Russia ].

PMID- 15150985
TI  - [Characteristics of the behavior of Helicobacter pylori colonies in the human
      body].

PMID- 15150986
TI  - [Alleviation of the competition stress in athletes after verbal psychological
      regulation].

PMID- 15150987
TI  - [Dynamics of the salivary macro-ions in humans undergoing social deprivation].

PMID- 15150989
TI  - Care homes' medicines management under fire from inspectors.

PMID- 15150988
TI  - [Clinical aspects of the use of magnetic encephalography].

PMID- 15150990
TI  - Emergency care for older people 'needs improving'.

PMID- 15150991
TI  - Commons committee to focus on palliative care.

PMID- 15150992
TI  - The single issue.

PMID- 15150993
TI  - Changing names, changing culture?

PMID- 15150994
TI  - A little bit of magic.

PMID- 15150995
TI  - Hip protectors: interpreting the evidence and addressing practicalities.
AB  - Some evidence suggests hip protectors are helpful in reducing fractures among
      older people. But, says Nicky Hayes, issues of compliance, tissue viability, cost
      and product design all need to be considered by nurses considering the
      implementation of hip protection strategies.

PMID- 15150997
TI  - Nitrates and their use with older people.

PMID- 15150996
TI  - Person-centred assessment with older people.
AB  - This article describes the principles behind the assessment of older people's
      needs and the challenges inherent in developing a person-centred framework for
      assessment. It suggests that person-centred assessment calls for skilled,
      empowered and well-supported nurses who are able to work in creative, innovative
      ways and who recognise that the needs of the older person are at the centre of
      all therapeutic working.

PMID- 15150998
TI  - Caring in partnership.

PMID- 15151000
TI  - Is Essence of Care making a difference?

PMID- 15150999
TI  - Nurses debate how to handle violence.

PMID- 15151001
TI  - Enhancing nurse communication.

PMID- 15151002
TI  - Taking a lead role in gynaecology care. Interview by Victoria Hoban.

PMID- 15151004
TI  - What you need to know about ... hepatitis A.

PMID- 15151003
TI  - The role of exercise in falls prevention for older patients.
AB  - Falls prevention is a key area of health promotion that is familiar to all nurses
      who work with older people. However, the suggestion that t'ai chi should be used
      as a prevention intervention may be new to many nurses. The evidence supporting
      t'ai chi and many other forms of exercise have been evaluated within the National
      Institute for Clinical Evidence (NICE) falls guidance. This should enable nurses
      to look at the prevention interventions that they currently recommend and
      question the evidence for or against their effectiveness. Nurses should also be
      able to identify factors that may present as barriers to participation.

PMID- 15151005
TI  - The use of phosphate enemas in the treatment of constipation.
AB  - Phosphate enemas are commonly used by community nurses in the treatment of
      constipation. This article reports on a literature review of evidence relating to
      their use. No evidence was found to support the use of these enemas conclusively,
      although a number of articles reported risks, contraindications, and
      complications. Phosphate enemas should therefore be used with caution and nurses
      should be aware of the contraindications associated with their use.

PMID- 15151006
TI  - How users and carers view their involvement in nurse education.
AB  - User and carer participation in health care is central to care planning and
      delivery. From an educational perspective, their input is beneficial in terms of
      enhancing the quality of the education process. The study reported in this paper
      explored the experiences of user and carer participation in nurse education from
      the perspective of the key stakeholders involved in the process. By pinpointing
      key issues of concern for participants, the study aims to help inform the ongoing
      development of practice in this area.

PMID- 15151007
TI  - The assessment and treatment of patients with chronic pain.
AB  - Chronic pain is an illness in its own right, with its own signs, symptoms, and
      complications. It has biological, psychosocial, physical, and emotional
      dimensions and due to its complexity it is often poorly understood. In many cases
      treatment cannot rely purely on the medical model of analgesic drugs but must
      encompass the management of all the other factors resulting from the pain. This
      article discusses the assessment of chronic pain, and the range of treatment
      methods available.

PMID- 15151008
TI  - The correct positioning and role of an external fixation device on a PEG.
AB  - A percutaneous endoscopic gastrostomy tube (PEG) is the means by which long-term
      artificial enteral nutrition can be provided to patients. PEGs differ in design
      and length of use but have one device common to all--the external fixation device
      or boister. This is a small piece of polyurethane or silicone that is usually
      circular or triangular in shape. It encircles the PEG and is designed to anchor
      the PEG externally and 'prevent it from being pulled into the stomach'
      (Colagiovanni, 2001) (Fig 1).

PMID- 15151009
TI  - The diagnosis and management of adult neurogenic dysphagia.
AB  - Swallowing is a complex sensorimotor process that involves the transport of
      material from the mouth to the stomach for digestion. It is also involved in
      protecting the airway and in rejecting noxious ingested substances. Humans
      swallow on average once every minute and this is supplemented by the production
      of saliva. When we eat, swallowing increases dramatically (six to eight times a
      minute).

PMID- 15151010
TI  - Legal issues concerning the withholding of feeding from patients.
AB  - The law surrounding the withholding or withdrawal of feeding from patients is
      complex and dependent upon case law (also known as common law or judge-made law).
      There are no statutory provisions and the leading case in this area is the Tony
      Bland case (Alredale NHS Trust v Bland, 1993).

PMID- 15151011
TI  - Implementation of the Malnutrition Universal Screening Tool.
AB  - A screening tool designed to identify patients at risk of malnutrition across the
      whole range of health care settings is gradually becoming established in
      practice. The Malnutrition Universal Screening Tool (MUST) was developed by the
      Malnutrition Advisory Group and is endorsed by the British Dietetic Association,
      the RCN, and the Registered Nursing Home Association.

PMID- 15151013
TI  - Broaden your skills with volunteering.

PMID- 15151012
TI  - The pharmacological effects of novel nutrients on the immune system.
AB  - The role of novel nutrients that appear to have pharmacological effects on the
      immune system has been studied over the past 20 years. This area of research has
      been termed immunonutrition. This paper provides an overview of particular novel
      nutrients--argtnine, glutamine, omega-3 fatty acids, and nucleotides--and
      examines some of the evidence for the effects that they may have on immune
      function. The benefits to particular patient groups are also considered (Box 1).

PMID- 15151014
TI  - Leading light.

PMID- 15151015
TI  - Growing season.

PMID- 15151017
TI  - Means of consent.

PMID- 15151016
TI  - A day to remember.

PMID- 15151018
TI  - Being in the know.

PMID- 15151019
TI  - Say goodbye to core values.

PMID- 15151021
TI  - Driven behaviour.

PMID- 15151020
TI  - Hospitals play havoc with a patient's common sense.

PMID- 15151022
TI  - Educating home carers on faecal continence in people with dementia.
AB  - AIM: To measure the effect of education on the knowledge of home carers in
      maintaining faecal continence for people with dementia. METHOD: The quasi
      experimental study involved pre-testing of carer knowledge, educational
      intervention and post-testing of their knowledge. The Carer Knowledge
      Questionnaire, specifically developed for use in the study, measured pre- and
      post-intervention knowledge levels. Knowledge scores and associations between
      categorical variables of interest were analysed. RESULTS: Before education,
      carers demonstrated high knowledge levels of factors that can cause faecal
      incontinence and low knowledge levels of strategies to promote and maintain
      faecal continence. Post-testing revealed a statistically significant increase in
      total knowledge scores (p < 0.001). Specifically, knowledge regarding faecal
      continence increased in four main areas: contributing factors, implications of
      constipation, effectiveness of specific strategies and awareness of factors
      unrelated to dementia that can have an impact on faecal continence. CONCLUSION:
      Education of home carers has been shown to increase knowledge of faecal
      continence.

PMID- 15151023
TI  - Implementing triage in a children's assessment unit.
AB  - The use of a triage system for patients attending A&E departments is an
      established practice. However, the use of such a system in assessment units is
      less formal and often left to individual clinical judgement. This article
      describes how the Manchester Triage System (MTS) was introduced, audited and
      adopted in a children's assessment unit (CAU) at the Royal Gwent Hospitals.

PMID- 15151024
TI  - Travel vaccination: an update.
AB  - Foreign tourism and travel are increasing in popularity, with more than six
      million visits being made to developing countries annually (ONS 2002). In this
      article, Jeannett Martin outlines the vaccine-preventable diseases associated
      with foreign travel and discusses routine vaccination required-for-entry vaccines
      and recommended vaccines.

PMID- 15151025
TI  - Beating the bullies.

PMID- 15151026
TI  - Climbing high.

PMID- 15151027
TI  - Suicide in Canada's immigrant population.
AB  - OBJECTIVES: This article compares suicide in the immigrant and Canadian-born
      populations. DATA SOURCES: The suicide data are from the Canadian Vital
      Statistics Data Base and the World Health Statistics Annual of the World Health
      Organization. The socio-demographic information used to determine denominators
      for suicide rates in Canada comes from the Census of Population. ANALYTICAL
      TECHNIQUES: Age-standardized suicide rates by sex and place of residence were
      calculated for the immigrant and Canadian-born populations, as were age- and sex
      specific suicide rates. Three-year average rates, centred on census years 1991
      and 1996, were used. A weighted data set based on 8 of the top 10 countries of
      birth for immigrants to Canada was created for international comparisons.
      Differences between rates were tested for statistical significance. MAIN RESULTS:
      Suicide rates for the immigrant population were about half those for the Canadian
      born. Among immigrants, suicide rates increase with age; among the Canadian-born,
      suicide is a "younger" phenomenon. Although male suicide rates exceeded female
      rates in both populations, the difference was less pronounced among immigrants.
      The pattern of suicide among immigrants was more like that in their countries of
      origin than that of the Canadian-born population. Immigrants living in Toronto,
      Montreal and Vancouver had lower suicide rates than immigrants in other parts of
      Canada.

PMID- 15151028
TI  - Leading cancers--changes in five-year relative survival.
AB  - OBJECTIVES: Changes in five-year relative survival ratios for prostate, breast,
      colorectal and lung cancer cases are examined. Ratios for cases diagnosed in the
      1985-1987 period are compared with those for 1992-1994. Incidence and mortality
      rates between 1985 and 1999 are compared with changes in relative survival. DATA
      SOURCES: Data are from the Canadian Cancer Registry, the National Cancer
      Incidence Reporting System, the Canadian Mortality Data Base, and life tables.
      ANALYTICAL TECHNIQUES: Analysis was conducted using the maximum likelihood method
      of Esteve. Age-standardized ratios for a given cancer were calculated by
      weighting age-specific ratios to the age distribution of patients diagnosed with
      that cancer. Statistical tests were used to compare corresponding age-specific
      and age-standardized ratios across the two periods. National estimates exclude
      Quebec and New Brunswick. MAIN RESULTS: Between the 1985-1987 period and the 1992
      1994 period, increases in five-year age-standardized relative survival ratios
      were dramatic for prostate cancer, large for breast cancer, and somewhat smaller
      for colorectal cancer. There was little absolute change in the ratios for lung
      cancer.

PMID- 15151029
TI  - Influenza vaccination.
AB  - OBJECTIVES: This article compares influenza vaccination rates in 1996/97 and
      2000/01 and describes the characteristics of adults who were vaccinated. DATA
      SOURCES: The data on influenza vaccination are from the 1996/97 National
      Population Health Survey and the 2000/01 Canadian Community Health Survey, both
      conducted by Statistics Canada. Data on hospitalizations and deaths are from the
      Hospital Mortality Data Base and the Canadian Mortality Data Base, respectively.
      ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate rates of
      vaccination among seniors, people with chronic conditions, and the total
      population aged 20 or older. Multiple logistic regression was used to assess
      relationships between being vaccinated and selected characteristics. MAIN
      RESULTS: Between 1996/97 and 2000/01, the percentage of Canadians aged 20 or
      older who reported having had a flu shot the previous year rose from 16% to 28%.
      Rates were higher for seniors and people with chronic conditions. The odds of
      vaccination were high for residents of middle-to-high income households, people
      with at least some postsecondary education, former smokers, and people with a
      regular doctor. Smokers and people who reported their health as good to excellent
      had lower odds of being vaccinated.

PMID- 15151030
TI  - [Stenting in obstruction of superior vena cava; clinical experience with the self
      expanding endovascular prosthesis].
AB  - From August 1997 to December 2002, 14 consecutive patients with superior vena
      cava syndrome with the self-expanding endovascular prosthesis. Diagnoses were
      adenocarcinoma in 6, small cell carcinoma in 4, squamous cell carcinoma in 1,
      metastatic lung cancer in 2, and invasive thymoma in 1. Atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP) were measured on their
      admission and perioperative period. Expecting only 1 patient complete
      symptomatically relieved within 3 days of stent implantation. Superior vena cava
      pressure or radial pressure of the stent was sufficient to relieve obstruction.
      Preoperative ANP level were normal, BNP level were increased. Postoperatively
      both ANP level and BNP level were slightly increased under intravenous dopamine
      hydrochloride. Implantation of the self-expanding stent endovascular prosthesis
      for superior vena cava syndrome provides rapid symptomatic relief and improves
      the patient's quality of life.

PMID- 15151031
TI  - [Early and late results of combined valvular and coronary artery surgery].
AB  - A total of 42 patients with combined valvular and coronary artery surgery were
      examined to analyze risk factors for cardiac related events and late deaths.
      There were aortic valve disease in 26 patients and mitral valve disease in 16.
      Preoperatively, 14 patients (33%) had cardiac dysfunction (ejection fraction < or
      = 40%) and 10 patients (24%) were in New York Heart Association (NYHA) functional
      class IV. There was no operative death with 96% of early graft patency. There was
      8 late deaths during 5.6 years of mean follow up. Actuarial survival rate was 86%
      and 64% after 5 and 10 years, respectively. Cardiac dysfunction was a significant
      independent predictor for late death. Cardiac related events occurred in 9
      patients. Freedom from cardiac related events was 78% and 59% after 5 and 10
      years, respectively. Cardiac dysfunction and mitral valve surgery were
      significant independent predictors for cardiac related events. Late result of
      combined mitral and coronary artery surgery was unfavorable in patients with
      cardiac dysfunction.

PMID- 15151032
TI  - [True pulmonary carcinosarcoma suspected as a metastatic lung tumor].
AB  - This patient, a 53-year-old man, has underwent operation on the diagnosis of
      esophageal cancer 2 years ago. An abnormal shadow was detected in the left lung
      field and he was admitted to our hospital for further examination. On the
      suspicion of metastatic lung tumor by transbronchial brushing cytology, partial
      resection of the left lower lobe was performed. Histologically the tumor was of
      carcinomatous (squamous cell carcinoma and adenocarcinoma) and sarcomatous
      (fibrosarcoma and chondrosarcoma) elements, so the patient was diagnosed as
      "true" pulmonary carcinosarcoma. True pulmonary carcinosarcoma is one of the very
      rarest neoplasms of the lung.

PMID- 15151033
TI  - [Subpectoral implantable cardioverter defibrillator implantation in a 20 kg
      weighted child].
AB  - An 11-year-old boy (weight 20 kg, height 124 cm), who was survived from
      ventricular fibrillation due to hypertrophic cardiomyopathy, admitted to our
      institution for implantable cardioveter defibrillator (ICD) implantation. We
      implanted a transvenous single coil lead and a device (Medtronic model 6943, GEM
      II VR 7229 Cx) in the subpectoral pocket. We selected this system because of less
      restriction on normal cardiac function, low operative morbidity, and expectation
      of long-term defibrillation threshold stability. Subpectoral implantation is
      cosmetically acceptable comparing with abdominal area. Lead insertion by cut-down
      technique is feasible and recommended to avoid lead-related complications. ICDs
      are infrequently used in pediatric patients and prospective study with long-term
      follow-up will be required to ascertain the prognosis for young survivors from
      sudden cardiac death.

PMID- 15151034
TI  - [Safety and efficacy of autologous blood donation before elective off-pump
      coronary artery bypass grafting].
AB  - BACKGROUND: Preoperative autologous blood donation reduces exposure to homologous
      blood transfusions in cardiac surgery. The purpose of this study was to
      ascertain, how much volume of predonated autologous blood needed to avoid of
      homologous blood transfusion in scheduled off-pump coronary artery bypass
      grafting (OPCAB). METHOD: Fifty patients underwent scheduled OPCAB. These
      patients donated 400 ml (group A, n = 30) or 800 ml (group B, n = 20) of
      autologous blood before operation. These patients donated at a rate of 400 ml per
      week. All patients were given an equal volume of saline solution at the time of
      autologous donation. RESULT: There were no significant differences mean age, mean
      body weight, mean preoperative hematocrit values, mean graft number or mean
      volume of intraoperative blood loss between groups A and B. There was significant
      difference the mean postoperative day-7 hematocrit value (33.4 +/- 1.5% vs 38.7
      +/- 1.5%, p < 0.05). The rates of avoiding homologous blood transfusion were
      63.3% in group A and 100% in group B (p < 0.05). CONCLUSIONS: Autologous blood
      transfusion was effective for reducing the homologous blood requirement. We
      believe that 800 ml predonation is sufficient to avoid homologous blood
      transfusion in scheduled OPCAB, further patients with cardiovascular disease
      including severe coronary artery should be donated with the administration of
      saline.

PMID- 15151035
TI  - [Intraaortic balloon pumping in patients undergoing coronary artery bypass
      grafting].
AB  - Beneficial effect of preoperative intraaortic balloon pumping (IABP) treatment in
      high-risk patients who had open heart surgery have been demonstrated. The purpose
      of this study is to determine the impact of preoperative IABP use on survival in
      high-risk patients undergoing coronary artery bypass grafting (CABG). METHODS:
      Two hundred seventy-seven consecutive patients having CABG at our institution
      were reviewed. Patients having an IABP were identified retrospectively and
      grouped into one of 3 groups as follows. Group A (n = 14): preoperative IABP for
      high-risk urgent or elective cases. Group B (n = 26): preoperative IABP for
      emergency cases. Group C (n = 6): unplanned intraoperative or postoperative IABP.
      RESULTS: Forty-six patients had an IABP (16.6% of total). Parsonnet score in
      group B was significantly higher (p < 0.05). Length of operation for group C was
      significantly longer (p < 0.05). Overall hospital mortality in the total group of
      277 cases was 4.2%. Hospital mortality was 7.1% in group A, 7.7% in group B, and
      50% in group C. Hospital mortality in group C was significantly higher (p <
      0.01). CONCLUSIONS: The beneficial effect of preoperative treatment with IABP in
      high-risk patients undergoing CABG was confirmed. This approach resulted in a
      significantly lower hospital mortality.

PMID- 15151037
TI  - [One-staged operation for mitral regurgitation and annuloaortic ectasia without
      aortic regurgitation with Marfan syndrome; report of a case].
AB  - A 32-year-old man with Marfan syndrome was admitted to our hospital for detail
      examination of congestive heart failure. Doppler echocardiography showed severe
      mitral regurgitation due to prolapse of posterior mitral leaflet. Annuloaortic
      ectasia without aortic regurgitation was also detected by aortography.
      Considering the future operative need for aortic root and ascending aorta, we
      performed mitral valve replacement with a mechanical valve and preventive
      concomitant aortic root replacement with a composite valve graft. His
      postoperative course was uneventful. Optimal surgical treatment of mitral
      regurgitation and annuloaortic ectasia in Marfan syndrome is controversial
      because the underlying connective tissue defect theoretically might compromise
      repair durability. Several surgical options for mitral regurgitation and
      annuloaortic ectasia in Marfan syndrome are discussed.

PMID- 15151036
TI  - [Computed tomography findings of pulmonary benign lesion in the peripheral
      region].
AB  - We evaluated computed tomography (CT) images in 22 cases of pulmonary granulomas
      less than 2 cm in diameter which preoperative diagnosis was difficult. In these
      lesions, air-containing type, irregular undulation of margin, pleural
      indentation, accompanying shadow and involvement of pulmonary artery was observed
      on CT images. The accompanying shadow and the absence of pulmonary vein relate to
      the lesion may have relevance in pulmonary benign lesion.

PMID- 15151038
TI  - [Unstable angina pectoris associated with systemic lupus erythematosus and
      arterio-sclerotic obstruction in whom hemophagocytic syndrome appeared after
      emergent operation; report of a case].
AB  - A 45-year-patient who suffered from old myocardial infarction (OMI) associated
      with systemic lupus erythematosus (SLE) and arterio-sclerotic obstruction (ASO)
      had unstable angina. Emergent coronary artery bypass grafting (CABG) was
      performed using saphenous vein graft because the left inter mammary artery was
      possible to be the collateral source for ASO. A high grade fever occurred without
      return of SLE 9 days after the operation. Pancytopenia simultaneously occurred.
      Hemophagocytic syndrome was diagnosed by the bone marrow examination. Pulse
      therapy with steroids was given and it was remarkably effected. Hemophagocytic
      syndrome has high mortality. However, it is difficult to distinguish from the
      other disease with high fever and bone marrow suppression in early period.
      Therefore, bone marrow examination was required to diagnose and to start the
      appropriate therapy as soon as possible.

PMID- 15151039
TI  - [Surgery for acute aortic dissection concomitant with preceding axillofemoral
      bypass to prevent malperfusion of visceral organs and limb ischemia].
AB  - A 52-year-old man was admitted with sudden onset of epigastralgia. Abdominal X
      ray showed dilated intestine and computed tomography (CT) revealed extended type
      A aortic dissection. Marked abdominal distention and weak pulse of right femoral
      artery were recognized so malperfusion of visceral organs due to narrowing true
      lumen compressed by thrombosed false lumen was suggested. In the operation, right
      axillo-right femoral bypass was established preceding to median sternotomy. This
      graft was used as an arterial perfusion site of cardiopulmonary bypass, and
      replacement of the ascending aorta was performed under hypothermic circulatory
      arrest and retrograde cerebral perfusion. Sign of malperfusion of visceral organs
      was showed for several days after the operation but it disappeared without
      further intervention. Axillofemoral inflow of cardiopulmonary bypass may be
      effective procedure in these cases.

PMID- 15151041
TI  - [Aortic valve regurgitation associated with rheumatoid arthritis; report of a
      case].
AB  - We report a rare case of aortic regurgitation (AR) associated with rheumatic
      arthritis (RA). A 59-year-old female was brought to our hospital with
      cardiopulmonary arrest because of severe heart failure due to AR. After being
      treated for heart failure, aortic valve replacement was carried out with a
      Carpentier-Edwards 21 mm model. During operation, it was observed that all of the
      coronary cusps had become thickened and shortened. A part of the right coronary
      cusp near the commissure of the left coronary cusp was especially badly affected.
      Valve histology showed a typical degeneration pattern. The patient had an
      uneventful postoperative course. It appears likely that the aortic valve had
      become shortened during the recovery process from inflammation caused by RA. The
      use of bioprostheses is beneficial in RA patients with aortitis, gastric ulcers,
      etc., since they reduce dynamic stress and eliminate the need for use of anti
      coagulants.

PMID- 15151040
TI  - [Acceleration of aortic regurgitation due to localized aortic dissection; report
      of a case].
AB  - We successfully treated a patient with accelerated aortic regurgitation due to
      localized aortic dissection with mitral regurgitation causing congestive heart
      failure. A 58-year-old female, who had suffered from aortic regurgitation for
      more than 10 years, had acute heart failure due to acceleration of aortic
      regurgitation. The surgical findings showed prolapse of the aortic valve due to
      localized dissection in the sinus of Valsalva. We performed a Bentall operation
      and a mitral valve replacement, with a favorable outcome. The postoperative
      course was uneventful.

PMID- 15151042
TI  - [Arch aneurysm after coronary artery bypass grafting, report of a case].
AB  - A 63-year-old woman had undergone graft replacement for abdominal aortic aneurysm
      in 1992, and coronary artery bypass grafting (CABG) using saphenous vein grafts
      in 1995. At that time arch aneurysm (4.7 cm) was pointed out. Chest computed
      tomography (CT) showed dilated arch aneurysm (7 cm) in 2000. We performed an
      operation for arch aneurysm. As the bypass graft to obtuse marginal branch was
      close to aneurysm, aortic closs clamp was impossible. So we injected potassium
      chloride to aortic root and cardiac arrest was obtained. Total arch replacement
      for arch aneurysm was performed and postoperative course was uneventful.

PMID- 15151043
TI  - [Ruptured thoracic aortic aneurysm presenting as massive epistaxis; report of a
      case].
AB  - An 80-year-old woman was transported to the emergency room at our hospital by the
      ambulance, suffering from massive epistaxis. As the patient was hemodynamically
      stable, otolaryngologist attempted to perform tamponade using nasal packing.
      However, the patient's condition deteriorated, with the development of dyspnea
      and a reduction in oxygen saturation to 90%. A chest X-ray performed at this
      point revealed left lung consolidation and pleural effusion while chest computed
      tomography (CT) demonstrated that rupture of a descending aortic aneurysm with
      periaortic hematoma and extension of hemorrhage into the left lower lobe of the
      lung. Emergency surgery was performed under partial extracorporeal circulation,
      established by cannulation of the right femoral artery and vein. In addition to
      the replacement of the descending aorta with a prosthetic conduit, left lower
      lobectomy was necessary because of severe adhesion to the descending aorta. The
      postoperative course was largely uncomplicated apart from development of
      chylothorax, which resolved with a short period of total parenteral nutrition and
      she was discharged 50 days after surgery.

PMID- 15151045
TI  - [Off-pump coronary artery bypass via left thoracotomy in patient with infective
      pancreatic fistula after surgery for bile duct carcinoma; report of a case].
AB  - A 62-year-old man with infective pancreatic fistula after surgery for bile duct
      carcinoma underwent off-pump coronary artery bypass (OPCAB) through left
      thoracotomy to avoid the use of cardiopulmonary bypass and the postoperative
      mediastinitis, since this patient has infective pancreatic fistula close to the
      xiphoid process. The coronary arterial revascularizations were performed: left
      internal thoracic artery to left anterior descending branch and saphenous vein
      graft to descending thoracic aorta. The aortic mechanical anastomosis device,
      aortic connector, was utilized the proximal anastomosis of saphenous vein graft
      so as to avoid aortic clamp, while the distal anastomoses were completed with
      stabilizer and apical retraction device. Postoperative angiogram showed both
      grafts were patent. No signs of infection or recurrence of malignant neoplasm was
      observed. OPCAB via left thoracotomy is one of useful options for patients in
      whom median sternotomy is not suitable approach for myocardial
      revascularizations.

PMID- 15151044
TI  - [Infected thoracoabdominal aortic aneurysm; report of a case].
AB  - A 54-year-old man complained of pain in the left upper abdomen with fever. His
      past medical history was significant for non-insulin-dependent diabetes mellitus
      and hypertension. Leucocytosis and an elevation of CRP levels were detected.
      Thoracoabdominal aneurysm of 69 mm in diameter was identified by enhanced
      computed tomography (CT). An infected thoracoabdominal aortic aneurysm was
      diagnosed and an emergency operation was performed. The aneurysm was treated by
      debridement of the infected aortic tissue and in situ prosthetic graft
      replacement followed by antibiotic therapy. The postoperative course was
      uneventful and there were no adverse neurological symptoms. After surgery,
      antibiotics were administered for 1 month intravenously and the patient was
      discharged on oral antibiotics for 2 months after the operation. The patient is
      doing well 7 months after the operation.

PMID- 15151047
TI  - [Mucinous adenocarcinoma of the anterior mediastinum].
AB  - The authors report are a rare case of primary mucinous adenocarcinoma of the
      anterior mediastinum in a 34-year-old Japanese woman. Routine chest radiography
      revealed an abnormal mass lesion in the left upper mediastinum. Her serum CA 19-9
      level was elevated at 299 (normal < 37) U/ml. The large tumor in the anterior
      mediastinum, 8 cm in diameter, were made of multicystic part with thick wall and
      thick spetrum and solid part in chest computed tomography (CT). Teratoma was
      suggested by percutaneous needle biopsy under CT scanning. When the chest was
      opened through a median sternotomy, adding a left collar incision, we found a
      hard tumor occupying the superior anterior mediastinum and then resected the
      tumor together with the left brachiocephalic vein, the left pleura, the
      pericardium and the left phrenic nerve because of invaded them. Grossly, the
      tumor was 13 x 10 x 8 cm and weighted 400 g. Pathologic diagnosis was mucinous
      adenocarcinoma of the anterior mediastinum. No primary cancer lesions were found
      in pancreas, ovarium, gastrointestinal tract and mammary gland. Microscopic
      examination showed minimal atypia site in mucinous adenocarcinoma and normal
      thymic tissues surrounding this tumor. These findings have led this case to
      conclude the primary tumor of thymus.

PMID- 15151046
TI  - [Thymic carcinoma incidentally detected on routine chest computed tomography;
      report of a case].
AB  - We reported a case of thymic carcinoma. A 61-year-old man was admitted to
      evaluate an abnormal shadow of lung field by chest X-ray. Routine chest computed
      tomography (CT) showed no abnormal findings on the lung field, but thymic tumor
      was incidentally detected. We suspected thymoma, performed a mediansternotomy and
      thymectomy with partial resection of pericardium. Pathological findings diagnosed
      undifferentiated carcinoma (large cell type) of thymus, the patient underwent
      radiation therapy of the mediastinum at a total dosage of 50 Gy and chemotherapy
      [cisplatin (CDDP) + vinorelbine ditartrate + mitomycin C (MMC)]. He has been
      doing well without recurrence for 2 years after the operation.

PMID- 15151048
TI  - [Acute pulmonary embolism after cesarean section; report of a case].
AB  - We present a case of acute pulmonary embolism (APE) after cesarean section. A
      cesarean section was performed on a 27-year old woman with normal course.
      However, one day after operation, she suddenly developed syncope and dyspnea.
      Soon after the symptom, she developed hypotension 60 mmHg. As a result of various
      examinations, her illness was diagnosed as APE with right ventricular dysfunction
      after cesarean section. She was consulted to our hospital for treatment. Soon
      after her arrival, we treated her for both APE and cardiogenic shock. The
      combined with antithrombotic therapy using heparin sodium, was successfully
      treated the patient from cardiogenic shock due to APE with right ventricular
      dysfunction after cesarean section.

PMID- 15151049
TI  - [Air embolism following computed tomography-guided lung needle marking; report of
      a case].
AB  - We report air embolism following computed tomography (CT)-guided lung needle
      marking. A 55-year-old man was admitted to our hospital with left pulmonary
      tumor, characterized as ground glass opacity (GGO). To localize the tumor, lung
      needle marking under CT guidance was performed. Almost immediately, the patient
      experienced symptoms of cerebral arterial air embolism. CT revealed air in the
      left ventricle. About 2.5 hours later the symptoms and the air disappeared. Three
      days later a video-assisted thoracoscopic wedge resection was performed. The
      patient's postoperative course was uneventful, and he was discharged in good
      condition.

PMID- 15151051
TI  - [Esophageal leiomyoma enucleated under the thoracoscopy; report of a case].
AB  - We report a case of a 40-year-old male with a posterior mediastinal mass that was
      8 cm in size and located behind the trachea. The thoracoscopic surgery was
      performed. The tumor was located from the level of left brachiocephalic vein to
      the carina. The mediastinal pleura over the tumor was longitudinally opened by
      cautery-scissors. The azygos vein lying over the tumor was divided by means of an
      endoscopic stapler. The muscular layer of the esophagus was also longitudinally
      opened. The tumor was enucleated. Then, the dissected proper muscle layer of the
      esophagus was suture-closed. The postoperative course was uneventful. On the
      first postoperative day Gastrografin was swallowed, showing the absence of leaks.
      The patient was discharged on the fourth postoperative day. The advantages of the
      thoracoscopic surgery are as follows: rapid, full recovery of the patient;
      decreased postoperative pain; short postoperative hospital stay. Esophageal
      leiomyoma in selected patient was suitable for thoracoscopic enucleation.

PMID- 15151050
TI  - [Pulmonary dirofilariasis resected by video-assisted thoracoscopy; report of a
      case].
AB  - A 35-year-old female was admitted for biopsy of abnormal shadow on chest X-ray.
      She was operated on for partial wedge resection of the right lower lobe by video
      assisted thoracoscopy without complication. Pathological findings in operation
      showed inflammatory benign tissues and suggested pulmonary dirofilariasis.
      Serologic examination was negative after operation, however histological
      diagnosis supported pulmonary dirofilariasis because a pulmonary artery embolism
      of calcified tissues consisted of non-human cells. There may be many cases due to
      old infections like this one, so it is important to consider it for diagnosis and
      perform more positive surgical procedures. We review a case of pulmonary
      dirofilariasis safely resected by video-assisted thoracoscopy for diagnosis by
      exclusion.

PMID- 15151052
TI  - Graduate degree program in nursing commemorates 30 years!

PMID- 15151053
TI  - [Subjective dimension of the professional in the humanization of health care: a
      thought].
AB  - This article reflects upon the humanization of health care, the demand for which
      is growing. It involves several complex and interdependent dimensions. The
      professional's subjective perspective and the interpersonal relationship are
      discussed and shown to be important factors in the humanization of health care.
      The necessity of professional's self-awareness and the awareness of their
      defenses are emphasized since they are considered to be important for the
      creation of an real encounter between professionals and patients. These topics
      are essential for the humanization and promotion of health care.

PMID- 15151054
TI  - [Rediscovering the ethics of care: focus and emphasis in the relationships].
AB  - The author presents a discussion of the meanings, the historical aspects and the
      different explanatory frameworks for the ethics of care. The main purpose is to
      contribute to the debate concerning the core role of care in nursing and nursing
      ethics. It also addresses the opposition between feminine and feminist ethics as
      an explanation for the secondary role of the ethics of care.

PMID- 15151055
TI  - [Ethics in the process of teaching-learning in obstetrical nursing].
AB  - This objective of this study was to observe ethics and solidarity in the teaching
      care process in women during prenatal care and childbirth. A centralized case
      study was carried out using critical-reflexive pedagogy. Thirty-nine nursing
      students and six teachers who taught theoretical-practice classes were
      interviewed at the Federal University of Ceara. The results showed that students
      and teachers are aware of the need for ethics competency and its applicability in
      care and that there is a need for new learning strategies to enable the student
      to develop interactive and human actions and solidarity. Updated care
      methodologies are needed that involve women as process participants and enable
      respect to their dignity.

PMID- 15151056
TI  - [Practice of nursing in the field of fertility regulation at a public health
      service].
AB  - This article is based on a doctoral dissertation that investigated the behavior
      of nurses concerning women's health in a public health care institution. It
      presents an experience in this practice regarding the actions of fertility
      regulation. The empirical data were obtained through reflection workshops and
      they were analyzed according to the discourse analysis technique and the gender
      theoretical approach. The analysis showed that in their practice, nurses value
      women's sexual and reproductive experiences, however, the institutional power,
      including here medical power, restrain their participation in the development of
      the autonomy and reproductive freedom of women.

PMID- 15151057
TI  - [The process of demedicalization of women's health care in nursing education].
AB  - This objective of this study is to present the pedagogic strategies adopted by
      the Rio de Janeiro State University Nursing School (UERJ--Brazil) for the
      demedicalization of care in nursing education in women's health. It presents the
      context of teaching in this area of knowledge. It also presents, from the
      perspective of concepts by Pierre Bourdieu, three spheres of students' and
      teachers' performance in this process.

PMID- 15151058
TI  - [Children's social representation of cancer].
AB  - This research was motivated by the need to know more about the care of children
      with cancer. The objective of the study was to discover what the social
      representation of the child with cancer are. Ten open interviews were conducted
      with children and teenagers from 9 to 15 years of age. The analysis issues that
      emerged from the children's discourse were about the disease, the treatment, the
      health care workers and family relationships. The present study presents the
      social representation of the disease, with the objective of better understanding
      the topic and directing nursing care towards a minimization of the trauma which
      this process brings upon the children.

PMID- 15151059
TI  - [Evolution of isolation in communicable diseases: knowledge in contemporary
      practice].
AB  - The identification of new infectious agents and the ever increasing expansion of
      known infections and diseases have been stimulating the revision of biosafety
      measures in the activities of professional health care workers. In the present
      article, the evolution of knowledge and practices of isolation and precautions
      were reviewed, which allowed us to recover the concepts and the interventions
      that were formulated and implemented. Since the beginning of the modern nursing,
      in the XIX century, the elements of the isolation practice for contagious
      diseases have remained basically the same. In other words, the emphasis on the
      use of mechanical, chemical and environmental barriers are given, based on
      inherent specificities of each part of the infectious chain process.

PMID- 15151060
TI  - [Physiopathologic aspects and nursing care in the rehabilitation of subjects with
      spinal cord injury].
AB  - Spinal cord injury can cause neurological damage such as alterations in the
      motor, sensitive and autonomic function. In this paper, details of clinical
      complications such as PVT, infection, respiratory insufficiency, pressure ulcers,
      autossomic disreflection, orthostatic hypotension, sphincteral-vesical and
      intestinal disfunctions, are related. And will also present prophylactic and
      therapeutic nursing care interventions designed for the well-being and
      improvement in life quality for patients.

PMID- 15151061
TI  - [Adaptation of an instrument to measure daily hours of home nursing care].
AB  - The Therapeutic Intervention Scoring System Intermediate: TISS-Intermediate, was
      translated into Portuguese and adapted to establish the number of hours daily of
      home care. The adaptation process of the instrument, developed with the Delphi
      Technique, used 16 nurses, who work in home care service providers and helped in
      calculating the number of nursing care hours for patients at their home after a
      period of hospitalization. At the end of the study, a 104 item-instrument was
      obtained for future clinical validation. This instrument will help nurses to
      extend nursing care to patients in their homes after they are discharged from
      hospitals, especially in regard to their decision-making concerning patient
      assessment.

PMID- 15151062
TI  - [Comparison of the profiles of hypertensive patients seen at the emergency
      department and in ambulatory care].
AB  - This study compares 100 hypertensive patients in emergency units with those who
      were seen in outpatient clinics. Hypertensive patients seen at the emergency unit
      showed to be different (p < 0.05) from those seen at the outpatient clinic
      regarding: higher blood pressure; lower income; not belonging to the hospital
      community; greater alcohol intake; became aware of their hypertension because
      felt bad; measured blood pressure less often; did not take the medicine more
      often. In conclusion, unfavorable characteristics can contribute to hypertensive
      patients who do not follow antihypertension treatment adequately, leading to care
      in emergency units.

PMID- 15151063
TI  - [Nursing students' knowledge about psychotropic drugs].
AB  - The objective of this study is to characterize the learning situation of nursing
      students with regard to psychotropic drugs. Students from a public and a private
      school were interviewed. Data analysis was thematic. The results do not suggest
      substantial differences between the schools regarding: learning centered on
      psychopharmacology; influence of media and use of common sense in the
      epidemiology; motivations and problems related to drug use; myth repetition and
      prejudice of users; disrespect of the social conflicts that involve drug
      problems. It is necessary to improve education on this topic so that students
      will have adequate knowledge to act as professionals.

PMID- 15151064
TI  - [Journal of the Nursing School of the University of Sao Paulo -- 36 years looking
      after the quality of nursing care].
AB  - REEUSP has been a trimestrial journal since 1998, which publishes 11 to 13
      articles per issue on different nursing subareas; most of them on teaching,
      health technology, adult health (in its different specialties), mental and
      psychiatric health. The article and research emphasis keeps on the hospital. For
      being linked to a teaching unit, it presents quality on its publishing; many
      times produced from thesis and dissertations. It faces the challenge of
      stimulating the publishing of authors from other institutions; for not becoming
      endogenous. On the last 10 years, it received and published articles from 18
      Brazilian states and several country cities from Sao Paulo State. Its graphic
      design was also remodeled for 2003, allowing higher clearness and easiness for
      reading. It accepts exchange with other journals and it is indexed on many basis.
      It was gotten a C international classification by CAPES.

PMID- 15151066
TI  - [Nosocomial infections under high surveillance].

PMID- 15151069
TI  - [Stoma therapy, stomas, dressings, care and complications].

PMID- 15151070
TI  - [Paradoxes of the nursing profession].

PMID- 15151071
TI  - [Evaluation of professional competences, an opportunity for the profession?].

PMID- 15151072
TI  - [Nursing professional channels].

PMID- 15151073
TI  - [The clinical nurse does not exist...in France].

PMID- 15151074
TI  - [Advanced practice and clinical nurse channels].

PMID- 15151075
TI  - [Giving meaning to care].

PMID- 15151076
TI  - [Developing clinical judgement through research].

PMID- 15151077
TI  - [An expertise practising in the patient's service].

PMID- 15151078
TI  - [Nurse clinicians, towards deepening of care].

PMID- 15151079
TI  - [Nursing consultation in stoma therapy, a clinical expertise path].

PMID- 15151080
TI  - [Which education for which nursing competences in the future?].

PMID- 15151081
TI  - [Cardiovascular system drugs. 2/12. Calcium inhibitors].

PMID- 15151082
TI  - [2/9 Rights of handicapped persons].

PMID- 15151083
TI  - [From obesity to type 2 diabetes, epidemiological landmarks].

PMID- 15151084
TI  - [Metabolic syndrome, definitions and physiopathology].

PMID- 15151086
TI  - [What goals in diet therapy for obesity and/or type 2 diabetes?].

PMID- 15151085
TI  - [Role of physical activity in the management of the obese patient].

PMID- 15151087
TI  - [Eating or pleasure, which to choose?].

PMID- 15151088
TI  - [Altering lifestyle and treating obesity, preventing type 2 diabetes?].

PMID- 15151090
TI  - [Screening of type 2 diabetes, the French guidelines].

PMID- 15151089
TI  - [Emergence of type 2 diabetes in children and adolescents].

PMID- 15151091
TI  - [National program of prevention and management actions of type 2 diabetes].

PMID- 15151092
TI  - [National diabetes health plan, point of view of a French Speaking Association of
      Diabetes and Metabolic Disease Research paramedic].

PMID- 15151093
TI  - [A cannulated articulating spacer--a functional implant for treatment of infected
      hip joint prostheses].
AB  - PURPOSE OF THE STUDY: Two-stage revision arthroplasty with the use of a spacer is
      generally accepted as a reliable method for treating infected hip replacements.
      Spacers made from antibiotic-loaded bone cement give good results in treatment of
      deep infections, but this technique is demanding in terms of spacer shaping. In
      addition, the conventional spacer may dislocate or fracture during patient
      mobilization. We attempted to avoid the disadvantages of conventional spacers by
      the construction of a cannulated articulating spacer. This is a special implant
      consisting of a polyethylene acetabulum, a stem, a modular neck and a head. Both
      the acetabulum and stem are covered with antibiotic-impregnated bone cement. They
      are subsequently pressed into the bone bed to make impression in the cement. The
      union of the bone bed with cement, which occurs in conventional implantation,
      must be avoided. This is achieved by making movements with the implant attached
      to an insertion handle, and by irrigating the operative field with large volumes
      of saline. A drain inserted in the canal running along the stem long axis
      facilitates continuous lavage of the medullary cavity. MATERIAL AND METHODS: A
      total of 11 patients with deep infection of a hip replacement were treated with
      the use of a cannulated articulating spacer in the years 2002 and 2003. Seven
      patients had late hematogenous infections and four had chronic delayed
      infections. The drains providing lavage stayed in place for about 10 to 12 days
      or less when three consecutive cultivations of drainage discharge were negative.
      Antibiotics were administered for at least 6 weeks according to the results of
      CRP and FW assessment. The reimplantation was planned on the basis of laboratory
      and clinical findings. The outcome was evaluated using the Harris hip score.
      RESULTS: Infection was successfully eradicated in all cases. The average time
      during which the cannulated articulating spacer was in place was 9.4 weeks. The
      results, as rated by the Harris hip score, were very good; after reimplantation,
      the average score was 95.1 points (range, 92 to 99). Even better evidence of the
      advantages of this method was provided by the increase in the average Harris hip
      score, which was 35.3 points (range, 26 to 69). No spacer dislocation or any
      other mechanical complication associated with the implant were recorded.
      DISCUSSION: Our results achieved with the cannulated articulating spacers
      developed in our department, as compared with conventional ones, show that the
      articulating spacer provides the patient with greater comfort and, therefore,
      improved quality of life for the period between the removal of a loose prosthesis
      and reimplantation of a definitive one. This method markedly reduces the risk of
      failure or dislocation of the temporary implant. In comparison with the PROSTALAC
      system, which is difficult to obtain and which requires complicated
      instrumentation, our method is simpler and less expensive. Our results show that
      the presence of an articulating spacer as a foreign body has no effect on the
      efficacy of treatment for deep infection. CONCLUSIONS: The procedure for
      preparing a cannulated articulating spacer described here is a modification of
      the method used to treat deep infection at the site of a total hip arthroplasty;
      it is inexpensive and provides markedly greater comfort for the patient. The
      technique combines the advantages of a two-stage revision involving spacer
      insertion with the use of lavage. Because patient have no major complaint and
      there is low risk of implant failure, the method allows us to adjust the
      reimplantation timing to the course of infection eradication and patients'
      overall health status.

PMID- 15151094
TI  - [Diclofenac 75mg. and 30 mg. orfenadine (Neodolpasse) versus placebo and
      piroxicam in postoperative analgesia after arthroscopy].
AB  - PURPOSE OF THE STUDY: Arthroscopy is often performed in an out-patient department
      or as one-day surgery. Opioids often used as postoperative analgesics may have
      unwanted side effects that may postpone the patient's discharge from hospital.
      This study was designed to evaluate a substitute for the most frequently used
      opioid pethidine. For pain relief, non-steroid anti-inflammatory drugs are
      recommended, but they offer a limited choice for parenteral administration. We
      used a new agent (Neodolpasse) based on diclophenac and orphenadine, and compared
      its efficacy with piroxicam and placebo. METHODS: A total of 119 patients
      scheduled for knee joint arthroscopy were included in this prospective study. In
      a randomized, double-blind manner, they received piroxicam (P), Neodolpasse
      (combining 75 mg diclophenac and 30 mg orphenadine; N) or placebo (C). The number
      of patients in groups P, N and C were 44, 35 and 40, respectively. The effect of
      therapy was evaluated on the basis of the following criteria: duration of post
      operative analgesia until a request for another analgesic, pain intensity (0-10
      VAS), side effects and the patient's satisfaction with analgesia. The efficacy
      was evaluated for 24 hours after arthroscopy; premedication and analgesia
      induction and administration followed the same anesthetic protocol in all groups.
      The ethic committee approved the study and patients gave their informed consent.
      The results were statistically evaluated using the ANOVA analysis of variance
      completed by a multiple comparison of levels of significance according to
      Bonferroni. The presence of side and unwanted effects was analyzed by the chi
      square of Fisher's exact test. A p value les than 0.05 was regarded as
      statistically significant. RESULTS: There were significant differences in the
      number of patients not requiring further analgesic medication after arthroscopy
      (P 52.3% vs. C (11.7%) p < 0.05, N (68.6%) vs. C p < 0.001), lower average
      postoperative pain (0 to 10-point scale, P 2.4 vs. C 2.9 p < 0.05, N 1.5 vs. C p
      < 0.05) and fewer side effects (N vs. both P and C, p < 0.05). DISCUSSION: The
      combination of diclophenac with orphenadine for intravenous application has only
      recently been available in the Czech Republic. The addition of a central muscle
      relaxant to a peripheral analgesic has a better effect than diclophenac alone.
      This may also account for a longer duration of analgesia in comparison with
      piroxicam reported to have significantly longer analgesic effects. The new
      medication also had fewer side effects. It was interesting to record that even
      the patients who had more pain and shorter postoperative analgesia were satisfied
      with the therapy provided. CONCLUSIONS: The main result of this study is the
      finding that Neodolpasse significantly reduces the intensity of postoperative
      pain and increases the duration of postoperative analgesia after knee joint
      arthroscopy.

PMID- 15151095
TI  - [Long-term results of unicompartmental knee joint replacement].
AB  - PURPOSE OF THE STUDY: To evaluate the long-term results of unicompartmental knee
      joint alloplasty (UKA) in a group of 21 patients. On the basis of their own
      results and literature data, the authors discuss effective strategies for
      treatment of unicompartmental osteoarthritis of the knee joint. MATERIAL: A group
      of 21 patients, who were implanted a total of 22 unicompartmental knee
      replacements, type St. Georg, Waldemar Link, between 1986 and 1992, were followed
      up till 2002. Since two patients living permanently abroad were excluded, the
      group at the final evaluation consisted of 19 patients with a total of 20 knee
      replacements. METHODS: In 2002, all patients were clinically and radiologically
      examined. They were interviewed about their subjective evaluation of the knee
      joint after alloplasty, and clinical and functional findings were assessed. The
      evaluation of long-term results was based on The Knee Society Clinical Rating
      System. RESULTS: The average Knee Score value was 84 points and average Function
      Score value was 78 points. Out of the 20 knee replacements evaluated, only one
      failure of UKA was recorded at 9 years after the primary implantation.
      DISCUSSION: The authors discuss the current state of treatment in
      unicompartmental knee arthritis and present several different views based on
      literature sources. Opinions on indications for specific surgical methods are
      still controversial. The authors draw attention to comparisons of long-term
      results between patients with UKA and patients who underwent high tibial valgus
      osteotomy or total knee replacement. They discuss the advantages and
      disadvantages of UKA in comparison with the other therapies. They also pay some
      attention to repeat surgery in failed UKA. CONCLUSIONS: UKA implantation is a
      surgical method of managing unicompartmental arthritis of the knee joint. The
      results presented by the authors and corroborated by many literature data provide
      evidence that UKA is of great importance in the treatment of unicompartmental
      knee arthritis. If a consistent selection of patients is maintained, a precise
      operation technique is used and a reliable implant is chosen, excellent immediate
      as well as long-term outcomes will be achieved.

PMID- 15151096
TI  - [Long-term results of the Schenker cementless femoral component].
AB  - PURPOSE OF THE STUDY: The aim of the work is to evaluate the results achieved in
      the group of patients with implanted Schenker cementless femoral component
      (Schenker, Switzerland) and discuss the method of solution of loosening of these
      components in the group of patients who underwent revision surgery. MATERIAL: The
      first part of the followed-up group comprised 16 patients (11 women, 5 men) with
      the total of 18 operated on hips who underwent primary hip arthroplasty between
      1989 and 1992 (Poidi cemented cup, Schenker cementless femoral component). The
      average follow-up period was 140 months (range 120 to 156 months). The second
      part of the group included patients who underwent revision for loosening of the
      Schenker cementless femoral component. This part consisted of 18 patients (11
      women, 7 men) with 20 operated on hips. The average interval after primary hip
      arthroplasty was 65 months (range 36 to 118 months). METHODS: In the period
      between May and December 2002, 34 patients were examined in the out-patient
      department. The evaluation involved only patients who did not undergo revision
      surgery. The clinical condition was evaluated on the basis of the Harris Hip
      Score and a radiograph was made to monitor any signs of linear wear of the cup,
      the extent of the radiolucent zone in both components and a potential migration
      of components. RESULTS: Results were evaluated in 16 patients (11 women, 5 men)
      with 18 operated on hips. The average follow-up period was 140 months. Harris Hip
      Score averaged 76 points (range, 56 to 97 points). The linear wear up to 1 mm was
      recorded in 4 cups and that of up to 2 mm in 2 cups. The radiolucent line
      surrounding the cup in zone III after DeLee and Charnley was present in 5 cups,
      in zones II and III in another 1 patient. No cup showed any signs of migration.
      The radiolucent line surrounding the femoral component was present in 9 hips. The
      progress of subsiding as compared to the preceding radiograph check (interval of
      1 to 2 years) was evident in 3 femoral components. At the time of the check 20
      femoral components had been already revised, of this 7 hips were after repeated
      revision. DISCUSSION: Between 1986 and 1992, 74 primary hip arthroplasties in 61
      patients were performed at the authors' department using Schenker cementless
      femoral component always in combination with Poldi cemented cup. Of 61 patients,
      the follow-up was not completed in 27 (10 patients died, 6 of them underwent a
      revision surgery at other hospitals, 11 patients were lost for the follow-up). In
      the evaluated 18 hips only 7 were without pain, another 3 patients from suffered
      occasional pain which responded to common analgesics. The results of clinical
      evaluation after Harris are unconvincing. During the follow-up 29 joints (39% of
      the original cohort) had been revised or indicated for revision surgery. Repeated
      revision surgery was performed in 7 hip joints where the Schenker cementless
      femoral component was originally replaced by cemented stem and this cemented
      component loosened within 3 to 7 years after the first revision. With regard to
      the success rate of other double tapered femoral components, the authors consider
      the material of the component (vitalium) as the main cause of failure. The
      surface of this stem did not provide for a long-term osteointegration and is at
      present successfully used only for production of femoral heads rather than for
      cementless femoral components. CONCLUSION: A favourable clinical finding and a
      good integration of the cementless femoral component Schenker were recorded
      within the average follow-up of 12 years only in 5 patients. All of them were
      young at the time of surgery and had a very good quality of bone. As a conclusion
      authors state that in general, Schenker cementless femoral component has not
      proved to be successful in clinical practice. For revision surgery of the
      loosened Schenker cementless femoral component it is necessary to use a titanium
      cementless component with a surface allowing long-term osteointegration.

PMID- 15151097
TI  - [Total endoprosthesis replacement after hip joint arthrodesis].
AB  - PURPOSE OF THE STUDY: To evaluate mid-term results of conversion of arthrodesis
      to total hip replacement in terms of X-ray findings and benefits for the patient.
      MATERIAL: Ten patients who had undergone hip joint arthrodesis were clinically
      examined and X-rayed and the findings evaluated. The most common indications for
      arthrodesis were posttraumatic lesions or the sequelae of a dysplastic hip joint,
      Perthes disease and inflammatory hip arthritis. The average age was 24.6 years
      (range, 15-37) at the first operation (arthrodesis) and 42.5 years (range, 30-61)
      at the second operation (hip arthroplasty). The average follow-up was 9.3 years
      (range, 1-16). Patients with true ankylosis of the hip joint were not included.
      METHODS: The patients were clinically examined for the range of motion, which was
      evaluated by Harris hip scores and X-ray findings. RESULTS: All eight patients
      who underwent total hip replacement due to persistent pain in the lumbosacral
      region experienced pain relief or its absence. This also applied to the patients
      whose X-ray films showed signs of spondylarthritis. The Harris hip scores showed
      that six patients were able to walk to longer distances without any support. No
      radiographic evidence of acetabular component loosening was found. One patient
      had to undergo reimplantation of the femoral component because of aseptic
      loosening. In the early postoperative period, one dislocation of the prosthesis
      and one sciatic nerve injury resulting in transient paresis of the peroneal nerve
      were recorded. None of the complications required repeat surgery. All patients
      reported that they would undergo the procedure again despite an increased risk
      associated with this procedure. DISCUSSION: Our results are in agreement with
      similar findings in this field. We did not find an increase in failed hip
      arthroplasty in older patients. The X-ray findings were very satisfactory,
      particularly those concerning the acetabular component. Patients who had true
      ankylosis of the hip joint were not included in the study. The average range of
      motion achieved in our patients corresponds to that reported in the literature.
      CONCLUSIONS: Conversion of hip arthrodesis to total hip replacement is not a
      frequent surgical procedure. It is associated with a higher degree of risk
      because of changed anatomy due to previous surgical interventions in that region.
      Motion restoration in the hip joint results in reducing low back pain and,
      consequently, improving the quality of life. All evaluated patients would be
      willing to undergo the operation again.

PMID- 15151098
TI  - [Arthroscopy in the diagnosis and therapy of wrist disorders].
AB  - PURPOSE OF THE STUDY: Arthroscopy of the wrist is a method facilitating the
      establishment of diagnosis in patients with wrist complaints which may also serve
      for surgical management of some of the causes of wrist pathology. The author
      presents his first experience with carpal arthroscopy as a diagnostic method as
      well as a therapeutic technique performed in one or two stages. MATERIAL: A total
      of 34 patients, 12 women and 22 men, in the age range of 14 to 64 years,
      underwent carpal arthroscopy. This was performed to treat acute or chronic
      conditions in 16 and 18 patients, respectively. METHODS: Arthroscopy was carried
      out with the hand in vertical traction, using distraction forces of 50 to 70 N,
      from the approach between the third and fourth or/and the fourth and fifth
      extensor compartments, in order to inspect the mediocarpal joint by an
      arthroscope with a diameter of 2.4 mm. Neither a tourniquet nor a pump was
      employed. When a lesion was detected, it was treated by arthroscopy or an open
      procedure in one surgical procedure. When indicated, further surgical
      intervention followed. RESULTS: The arthroscopic inspection revealed triangular
      fibrocartilagenous complex (TFCC) lesions in 18 patients. Injury to the scaphoid
      lunate (SL) ligament was found in 16 patients. One patient had a combined lesion
      of the triquetral-lunate and SL ligaments, two showed a SL lesion together with a
      distal radius fracture, three were diagnosed with pseudoarthrosis of the scaphoid
      bone and one with synovitis after rheumatoid arthritis. In two patients,
      adhesions in the radiocarpal joint following a fracture of the distal radius were
      found and shaved. A total of 22 patients were treated by arthroscopic surgery; 19
      underwent open procedures in one stage and five were indicated for secondary
      surgery. DISCUSSION: Wrist arthroscopy has been reported in the literature as the
      only method that can reveal damage to SL ligaments not shown by X-ray or magnetic
      resonance imaging examination. During arthroscopy, several interventions can
      directly be carried out by this procedure, such as treatment of the TFCC, and
      thus relieve the patient's complaints. Arthroscopy is irreplaceable in the
      diagnosis of dynamic carpal instability or injury to TFCC in ulnar-carpal
      impingement. Our experience suggests that arthroscopically-guided osteosynthesis
      of the distal radius has great prospects. CONCLUSIONS: In our hospital acute
      arthroscopy is indicated when carpal connective tissue lesions, potentially
      leading to wrist instability, are suspected, when damage to carpal ligaments is
      found by X-ray examination or when an acute TFCC lesion is suspected.
      Arthroscopically-guided osteosynthesis of the distal radius appears to be a
      prospective method. In patients with chronic complaints, wrist arthroscopy is
      indicated in suspected TFCC lesions with ulnar-carpal impingement, in chronic
      carpal synovitis, and before sperious operations on the carpal bones in order to
      ascertain the state of cartilage and plan the appropriate surgery.

PMID- 15151099
TI  - [The shape of the acromion and its effect on the subacromial space].
AB  - PURPOSE OF THE STUDY: A great variability of the shape of acromion exists in the
      population. The shape of the acromion plays a great role in development of the
      pathology of the subacromial space. Quantification of the anatomical changes
      using radiological examination (X-ray. CT) is a major contribution to the
      diagnosis of the subacromial space disorders and to differential diagnosis of
      painful affections of the shoulder. The aim of the study was to assess the
      prevalence of the degenerative changes in the subacromial space and their
      relation to the shape of the inferior space of acromion in our population.
      MATERIAL AND METHODS: In 50 randomly chosen cadavers during autopsy both
      shoulders where surgically explored in order to evaluate the changes on the
      rotator cuff and the changes on the major tubercule, on the tendon of the long
      head of biceps brachii in correlation to the shape of the inferior surface of
      acromion. RESULTS: Rotator cuff lesions of variable size were found in 16
      cadavers, in 10 cases the lesion was unilateral, in 6 cases bilateral. The
      lesions were more often seen in the older age group. With increasing concavity of
      the inferior surface of acromion not only the number of the rotator cuff lesions
      and degenerative changes in the subacromial space were increasing, but so was the
      amount of the changes. CONCLUSION: The shape of acromion and increasing concavity
      plays a major role in the development of the subacromial pathology, accelerate
      the degenerative changes in this space. Reshaping the undersurface of acromion
      and diminishing the concavity in first stages of clinical symptoms, which present
      mostly as impingement syndrome, is reasonable to prevent larger pathological
      deterioration in subacromial space. The authors conclude that according to the
      relation between the shape of the inferior surface of acromion and the amount of
      lesion an early operative procedure is valuable.

PMID- 15151100
TI  - [A rare shortening of the first metatarsus of the foot and its treatment with
      distraction arthrodesis].
AB  - Multiple toes may develop on the medial or lateral side of the forefoot or in its
      middle. This may involve duplication of only the distal phalanx or the whole
      hallux including the metatarsal. In a duplicated big toe, the phalanx to be
      maintained, because short muscles of the leg are attached to it, is usually
      localized medially. A rare case of dysplasia of the first metatarsus, following a
      resection indicated in childhood for a hallux triples, is described in a 20-year
      old girl. In order to remove hallux insufficiency and an overloading of the
      middle metatarsals, the authors decided to carry out a one-stage prolongation of
      the first metatarsal, using an autologous tricorticcal graft collected from the
      pelvis and a dynamic compression plate. No surgical treatment of the middle
      metatarsals was indicated because a disproportionate, short foot would result.
      Both the subjective and objective status of the patient at 6 months after the
      operation showed that the non-standard prolongation procedure was correctly
      indicated and allowed for physiological loading of the foot and restoration of
      normal walking.

PMID- 15151101
TI  - [Traumatic atlanto-occipital dislocation].
AB  - The authors present two cases of survival after atlanto-occipital dislocation
      (AOD). Atlanto-occipital dislocation is in majority of cases lethal and only
      rarely compatible with life. AOD is often missed mainly in polytrauma in
      unconscious patients when the life endangering injury detracts attention from the
      examination of the upper cervical spine. The authors point out to the fact that
      with the improvement of the work of the rescue service and a fast transport of
      the patient to the hospital the number of these injuries may be expected to grow.

PMID- 15151102
TI  - "Receptive substances": John Newport Langley (1852-1925) and his path to a
      receptor theory of drug action.

PMID- 15151103
TI  - Professionalism and the boundaries of control: pharmacists, physicians and
      dangerous substances in Canada, 1840-1908.

PMID- 15151104
TI  - Variolation, vaccination and popular resistance in early colonial south India.

PMID- 15151105
TI  - The Officiers de Sante of the French Revolution: a case study in the changing
      language of medicine.

PMID- 15151106
TI  - For the record: the Francis Crick Archive at the Wellcome Library.

PMID- 15151107
TI  - Will orthodontists become more involved in treating patients who have sleep
      apnea?

PMID- 15151108
TI  - Presentation of the Morris F Collen Award to William Edward Hammond II, PhD.

PMID- 15151110
TI  - AMIA President's Awards, 2003.

PMID- 15151111
TI  - On: Countertransference and transference in 'Two sessions with Catherine'.

PMID- 15151112
TI  - On: Transition to young adulthood: a prospective study.

PMID- 15151113
TI  - On: Hans Loewald: a radical conservative.

PMID- 15151114
TI  - An overview of advanced practice nurses.

PMID- 15151115
TI  - Medicare and state health care programs; fraud and abuse: OIG civil money
      penalties under the Medicare prescription drug discount card program. Interim
      final rule with comment period.
AB  - In accordance with section 1860D-31 of the Social Security Act, this rule sets
      forth the OIG's new authority for imposing civil money penalties (CMPs) against
      endorsed sponsors under the Medicare prescription drug discount card program that
      knowingly engage in false or misleading marketing practices; overcharge program
      enrollees; or misuse transitional assistance funds.

PMID- 15151116
TI  - Locomotion and its recovery after spinal injury in animal models.

PMID- 15151117
TI  - Cognitive rehabilitation in the 21st century.

PMID- 15151118
TI  - Recent advances in stroke rehabilitation.

PMID- 15151119
TI  - Abstracts of the 3rd World Congress in Neurological Rehabilitation, main theme:
      cognitive rehabilitation. Venice, Italy, April 6, 2002.

PMID- 15151120
TI  - [Use of maintenance fluid therapy in surgery].
AB  - OBJECTIVE: To analyze the use of various maintenance fluid therapy regimens, as
      well as their adequacy to hospital recommendations, in adult in-patients admitted
      to a general surgery ward during 1 year. MATERIAL AND METHODS: Data on solution
      type and volume, fluid therapy regimen, and duration in days were retrospectively
      collected for each administered solution from computerized medical orders within
      the Unit-Dose Drug Distribution Area. A database was developed including the
      composition of available solutions within our hospital, so that electrolytes,
      glucose and volumes administered may be calculated. RESULTS: Out of 354 patients
      undergoing fluid therapy 125 were selected to receive maintenance regimens. Fluid
      therapy was administered for more than 5 days in 31% of patients. The most
      commonly supplied fluids were 5% glucose (43%) and 0.9% saline + 1500 mL of 5%
      glucose + 60 mEq potassium chloride (CIK). Amongst patients receiving the
      recommended volume/day (84%) 50% received sodium and potassium more than twice as
      much the recommended amount, and 70% received glucose amounts not covering
      minimal daily requirements. Potassium was administered according to
      recommendations in 85% of patients. CONCLUSIONS: There is an excessive use of
      0.9% saline and 5% glucose to the detriment of 1/3 glucosaline and 10% glucose,
      which translates as an excessive daily sodium and defective daily glucose
      provision. In our hospital we have recommended maintenance fluid therapy
      regimens, as well as fluids more appropriate for postoperative electrolyte
      replacement; however, their use is still deficient.

PMID- 15151121
TI  - Speech, language, and reading skills after early cochlear implantation.

PMID- 15151122
TI  - Effect of expanded newborn screening for biochemical genetic disorders on child
      outcomes and parental stress.

PMID- 15151123
TI  - You're the flight surgeon. Ulcerative colitis.

PMID- 15151124
TI  - Inhaled nitric oxide in premature infants with respiratory distress syndrome.

PMID- 15151125
TI  - Randomised controlled trial of treatment of unilateral visual impairment detected
      at preschool vision screening.

PMID- 15151126
TI  - Autoimmune cytopenia in common variable immunodeficiency.

PMID- 15151127
TI  - Using pamidronate for osteoporosis.

PMID- 15151128
TI  - Cefuroxime-induced immune hemolysis.

PMID- 15151130
TI  - Validation of meconium fatty acid ethyl esters as biomarkers for prenatal alcohol
      exposure.

PMID- 15151129
TI  - Kawasaki disease mimicking an acute appendicitis.

PMID- 15151132
TI  - Practice-based teaching and learning: an example of academic-community
      collaboration.

PMID- 15151133
TI  - Raf kinase inhibitor protein: a prostate cancer metastasis suppressor gene.
AB  - Defining the mechanisms that confer metastatic ability on cancer cells is an
      important goal towards prevention of metastasis. A gene array screen between a
      non-metastatic prostate cancer cell and its metastatic derivative line revealed
      decreased expression of Raf kinase inhibitor protein (RKIP) in the metastatic
      cell line. This finding is consistent with the possibility that loss of RKIP is
      associated with metastasis. RKIP is expressed in many tissues including brain,
      lung, and liver. RKIP blocks Raf-induced phosphorylation of MEK. In addition to
      its modulation of Raf signaling, RKIP modulates both G-protein signaling and NF
      kappaB activity. The impact that RKIP has on multiple signaling pathways grants
      it the ability to play a role in several cellular functions including membrane
      biosynthesis, spermatogenesis, and neural signaling. Novel cellular functions for
      RKIP continue to be identified, several of which contribute to cancer biology.
      For example, RKIP promotes apoptosis of cancer cells, which suggests that loss of
      RKIP in cancer will protect cancer cells against cell death. Additionally,
      restoration of RKIP expression ina metastatic prostate cancer cell line does not
      effect primary tumor growth, but it does inhibit prostate cancer metastasis.
      These parameters identify RKIP as a metastasis suppressor gene, which suggest
      that it or proteins it interacts with are putative molecular targets to control
      metastasis. These findings are supported by the observation that RKIP expression
      is decreased in metastases of prostate cancer patients, compared to normal
      prostate or the primary prostate tumor. In this review, RKIP biology and its role
      in cancer will be described.

PMID- 15151134
TI  - Paying for quality: health plans try carrots instead of sticks.
AB  - Growing national attention to improving quality and patient safety is spurring
      development of quality-based financial incentives for physicians and hospitals.
      Health plans in particular are driving these pay-for-performance initiatives,
      according to findings from the Center for Studying Health System Change's (HSC)
      2002-03 site visits to 12 nationally representative communities. For now, there
      is little standardization across plans in how quality improvement is measured,
      and incentive payments typically are modest in comparison with providers' total
      revenue. Nevertheless, today's nascent efforts can provide a foundation on which
      to build. Support from major plans and public and private purchasers,
      sufficiently large financial incentives properly aligned with base provider
      payment systems, and improvements in quality measurement can all help foster
      widespread provider acceptance and, ultimately, improvements in health care
      quality.

PMID- 15151135
TI  - Medicare's chronic care improvement pilot program: what is its potential?
AB  - This paper describes the voluntary chronic care improvement program under
      traditional fee-for-service Medicare as authorized by the Medicare Prescription
      Drug, Improvement, and Modernization Act (MMA) of 2003 (Public Law 108-173;
      section 721). This brief analyzes the emerging issues raised by this new program,
      including which chronic conditions and regional areas will be targeted, the types
      of entities that may participate, the physician's role in care management, and
      the adoption and use of health information technology and evidence-based clinical
      guidelines.

PMID- 15151136
TI  - Obituary. Harold Kletschka.

PMID- 15151137
TI  - Consumer cost sharing in private health insurance: on the threshold of change.
AB  - Employers are asking employees to pay more for health care through higher premium
      contributions, share of contribution, and out-of-pocket maximums, along with
      variations in deductibles, co-pays, and coinsurance based on choice of providers,
      networks, drugs, and other services. This issue brief examines consumer cost
      sharing trends in private insurance, discusses the outlook for cost sharing in
      employment-based benefits, and considers public policies to support health care
      markets for consumers.

PMID- 15151138
TI  - [The "incorrect" laboratory result. II: Common misinterpretations of laboratory
      results].
AB  - In the second part of our review the most frequent misinterpretations of
      laboratory results in the daily clinical practise are discussed. Special
      attention has been given to frequent misinterpretations in the analysis of
      electrolytes, enzymes and hormones in plasma/serum (pseudohyperkalemia,
      macroenzymes, macroprolactinemia). Misinterpretations of the testing of blood
      gases, serum glucose, lipid concentrations, and calcium are described in greater
      detail. In addition, potential errors in the urinanalysis and the importance of
      adequate sampling of blood specimens for coagulation testing are described. The
      hematological results can be misinterpreted in the presence of EDTA-induced
      pseudothrombocytenia and of irregular immunoglobulines. Immunological methods
      themselves can lead to misinterpretations of the laboratory result, e. g. caused
      by the high dose hook effect and interferences in the presence of rheumatoid
      factor or HAMA. Finally clinical relevant errors in the therapeutic drug
      monitoring are discussed which are associated with the limited specificity of the
      antibodies in the commonly used immunological tests.

PMID- 15151139
TI  - [A 32-year old male patient with pathological humeral fracture, splenomegaly and
      thrombocytopenia].
AB  - We describe the case of a 32-year old male patient who presented with a
      pathological fracture of his right humerus, splenomegaly and thrombocytopenia,
      the typical symptoms of Gaucher's disease, a lysosomal storage disease. Diagnosis
      was confirmed by bone marrow biopsy (detection of lipid engorged macrophages -
      Gaucher cells), by a markedly diminished activity of acid, beta-Glucosidase and
      by showing two different mutations (764T/A, 1187G/A) in the gene encoding acid
      beta-Glucosidase. The first mutation causes an amino-acid substitution
      (phenylalanine to tyrosine). The second mutation causes a premature termination
      at amino-acid position 396. Enzyme replacement therapy was started with 60
      Units/kg body weight, because of severe bone symptoms. Following the decrease in
      spleen size and increase in platelet count the dose was gradually tapered to 20
      U/kg. After two years of enzyme replacement therapy platelet count and spleen
      volume have normalized and the bone lesions have almost disappeared.

PMID- 15151140
TI  - Plasmodium vivax Duffy binding protein: a modular evolutionary proposal.
AB  - The population of malaria-causing parasites is characterized by great genetic
      diversity. Knowledge of the polymorphism generation mechanism is a central issue
      for developing effective vaccines against malaria and understanding the parasite
      population structure. Plasmodium vivax genetic diversity has been explained in
      terms of two major factors: natural selection and intragenic recombination. A
      modular organization was found within P. vivax Duffy binding protein in the
      present work. Four Colombian isolates have identical sequences to Salvador-1
      strain amongst dpb regions III-VI analysed, suggesting a high identity between
      Central and South American isolates. Geographically clustered sectors,
      corresponding to cysteine-rich regions (II and VI), show a high sequence
      diversity that could reflect a possible immune response evasion mechanism; both
      positive and negative selection were detected in these regions. In contrast,
      other dbp gene regions display a non-geographical clustering pattern, lower
      sequence diversity and predominant negative selective pressure. Recombination was
      homogeneously detected all along the molecule. These findings suggest that
      diversification vs. homogenizing forces, drive dbp gene evolution and determine
      its mosaic region organization.

PMID- 15151141
TI  - Investigating antigenic variation and other parasite-host interactions in
      Plasmodium falciparum infections in naive hosts.
AB  - Mathematical models of the in-host dynamics of malaria infections provide a
      valuable tool to explore aspects of the host-parasite interaction that are not
      possible to investigate experimentally. This paper presents predictions of
      several important parameter values for 2 parasite strains/groups: parasite PfEMP1
      switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related
      to specific and non-specific host immune responses. A stochastic simulation model
      of the in-host dynamics of Plasmodium falciparum infections in naive hosts was
      used to make these predictions. This model incorporates a novel process to
      simulate antigenic variation by the parasite, and specific and non-specific
      immune responses by the host. Comparison of model output to a range of published
      statistics indicated that the model is capable of reproducing the features of
      clinical P. falciparum infections, including the characteristic recrudescent
      behaviour. Using the model, we explored the hypothesized switching mechanism of a
      fast overall rate of antigenic variation early in an infection and found that it
      is compatible with chronic infections when the var genes are split into 2 groups;
      fast and slow switching.

PMID- 15151142
TI  - Experimental infection of severe combined immunodeficient (SCID) mice with the
      human microsporidian Trachipleistophora hominis.
AB  - Different courses of microsporidiosis, related to the route of infection, were
      observed in severe combined immunodeficient (SCID) mice inoculated with spores of
      the human microsporidian Trachipleistophora hominis (Phylum Microspora). After
      eye contamination by spores the mice became moribund within 7 to 8 weeks, showing
      severe infection in the conjunctiva and cornea, and lighter infections in the
      urinary bladder, liver and spleen. The mean survival time of intramuscularly
      inoculated SCID mice was 12 weeks, when heavy infection was found in muscles
      around the site of inoculation, and also in several viscera. Subcutaneously
      inoculated SCID mice developed skin lesions around the inoculation sites, and
      heavy urinary bladder infection, and died 6 or 7 weeks after inoculation.
      Intracerebrally inoculated SCID mice became moribund 5 or 6 weeks after
      inoculation with massive infection in the urinary bladder and liver, but none in
      the brain. Intraperitoneally inoculated SCID mice survived for 13 weeks and the
      urinary bladder and liver were the most heavily infected organs. The SCID mice,
      inoculated perorally and examined after 23 weeks, were uninfected. Infection was
      not detected in the brain of any of the inoculated SCID mice. Our results show
      that T. hominis has very little tissue specificity. Peroral infection seems to be
      ineffective in T. hominis, but eye conta mination or insect bite (as mimicked by
      injection) are suggested as possible routes of infection under natural
      conditions.

PMID- 15151143
TI  - Extracellular matrix alterations in experimental murine Leishmania (L.)
      amazonensis infection.
AB  - Here we describe extracellular matrix alterations in footpad lesions and draining
      lymph nodes caused by Leishmania (L.) amazonensis in mouse strains with distinct
      susceptibilities to this parasite: BALB/c (susceptible), C57BL/6 (intermediate),
      and DBA/2 (resistant). Changes in ECM were observed mainly in BALB/c mice that,
      in general, presented tissue damage associated with high parasite burden. Under
      polarized light, Sirius Red revealed type I collagen that was predominant in the
      primary lesion in all strains studied at the early phase of infection, but
      gradually decreased and was replaced by abundant type III collagen fibres in
      chronic phase lesions. The presence of type III collagen seemed to provide
      support to inflammatory cells, mainly vacuolated and parasitized macrophages.
      Laminin expression was not altered during infection by L. (L.) amazonensis in any
      of the mouse strains studied. Furthermore, the decreased fibronectin expression,
      in all strains, in areas where amastigotes have been found, indicated that this
      decline was also not related to the genetic background.

PMID- 15151144
TI  - Toxoplasma gondii major surface antigen (SAG1): in vitro analysis of host cell
      binding.
AB  - Previous studies have indicated that SAG1, the major surface molecule of the
      protozoan parasite Toxoplasma gondii, is an important attachment ligand for the
      host cell. However, the research data that supports this claim comes largely from
      studies investigating tachyzoite binding, and not SAG1 binding per se. In this
      study we successfully developed an in vitro attachment assay to directly evaluate
      the mechanism of SAG1-host cell binding. Competition experiments were then
      performed using SAG1 that had been pre-treated with the neoglycoprotein BSA
      glucosamide or with antibody. Soluble BSA-glucosamide blocked SAG1 attachment to
      MDBK cells in a dose-dependent manner, implying that SAGI binding is mediated, in
      part, via attachment to host cell surface glucosamine. Interestingly, pre
      incubation of SAG1 in polyclonal sera from chronically infected mice failed to
      block binding. This challenges the assumption that anti-SAG1 antibodies block
      parasite attachment through the masking of SAG1 host cell binding domains. Taken
      together, this evidence presents new strategies for understanding SAG1-mediated
      attachment.

PMID- 15151145
TI  - MVA ROP2 vaccinia virus recombinant as a vaccine candidate for toxoplasmosis.
AB  - Toxoplasma gondii is the aetiological agent of toxoplasmosis and is the most
      frequent and best known of the parasitic diseases. In the United States, a
      serological survey from the Third National Health and Nutrition Examination
      Survey found that an estimated 23% of adolescents and adults have laboratory
      evidence of infection with T. gondii. Although toxoplasmosis is asymptomatic or
      shows self-limited symptoms in adults, in pregnant women infections can cause
      severe health problems to the fetus if the parasites are transmitted. Also, in
      immunodeficient patients, chronic infection with T. gondii can reactivate and
      produce encephalitis, which is frequently lethal. In addition, in veterinary
      medicine, T. gondii infection is of economic importance due to abortion and
      neonatal loss in sheep and goats. Recently, the development of vaccines against
      toxoplasmosis has progressed considerably. The live attenuated S48 strain of
      Toxoplasma has been broadly used for veterinary purposes. DNA vaccines containing
      the full-length of SAG1/P30, ROP2 or ROP1 genes have proved to be a promising
      candidate to induce protection against toxoplasmosis. Viral vectors have proved
      to be the best candidates for vaccination in different diseases. A recombinant
      Herpes virus carrying the ROP2 gene is able to induce protective immunity in
      cats. In the present work we describe the potential of the MVA ROP2 recombinant
      vaccinia virus as a vaccine against toxoplasmosis. MVA ROP2 induces antibodies
      against the ROP2 protein in similar amount and types as the thermo-sensible
      strain ts-4 of T. gondii, which is able to fully protect mice against challenge
      with the virulent RH strain of T. gondii. Also, the life-span of mice is
      increased in MVA ROP2 vaccinated animals. We conclude that MVA ROP2 vaccine can
      possibly generate an immune response, which could be useful in protection against
      toxoplasmosis.

PMID- 15151146
TI  - The current status of onchocerciasis in the forest/savanna transition zone of
      Cote d'Ivoire.
AB  - Onchocerca volvulus exists in at least two strains in West Africa, while its
      black-fly vectors consist of sibling species, dwelling in the savanna and
      forest/transition zones. In transition and degraded forest zones both parasite
      strains and different sibling species of the vector can be sympatric. The strain
      of parasite in infected humans and in vector black-flies was determined in two
      bioclimes along the Bandama river of Cote d'Ivoire. The upper Bandama is located
      in the savanna bioclime while the Middle Bandama is located in a degraded forest
      zone. At both sites, savanna-dwelling sibling species of the Simulium damnosum
      sensu lato species complex predominated. The severe-strain of O. volvulus was the
      predominant strain at both sites. However, severe-strain parasites represented a
      significantly larger proportion of those found in the vector population than in
      the human population in the degraded forest of the Middle Bandama. These data
      suggest that in degraded forest areas recently invaded by savanna-dwelling
      species of S. damnosunz s.l. transmission of the severe-strain of the parasite
      might be more efficient than transmission of the mild-strain.

PMID- 15151147
TI  - Electrocardiographic characterization in Trypanosoma cruzi reinfected mice.
AB  - Chagas' disease, caused by Trypanosoma cruzi, affects approximately 20 million
      people. There are 3 stages in the disease: acute, intermediate and chronic, the
      diversity and severity of the symptoms range from a mild electrocardiographic
      alteration to sudden death. We have previously demonstrated that when
      reinfections were carried out in the acute phase they produce greater cardiac
      damage. The aim of the present work was to investigate whether T. cruzi
      reinfected mice present electrocardiographic abnormalities that could be
      characteristic and only achieved after reinfections. Of the mice reinfected
      during the acute phase 100% showed abnormalities from days 90 post-infection,
      with a predominance of auricle ventricle blocks (67-71%). All the mice reinfected
      during the chronic infection showed electrocardiographic alteration after 30 days
      post-first reinfection. Of the mice infected, without reinfection, 60% exhibited
      electrocardiographic dysfunction at 90 days post-infection. Our results
      demonstrated that when the host was reinfected in the acute phase, more serious
      electrocardiographic alterations were developed than when the reinfections were
      carried out in the chronic stage. Sudden death described in some chagasic
      patients, might be related to some of the findings described here.

PMID- 15151149
TI  - Natural variation in the response of Caenorhabditis elegans towards Bacillus
      thuringiensis.
AB  - Almost nothing is known about the natural ecology of the nematode Caenorhabditis
      elegans, including its interactions with parasites. To help rectify this
      discrepancy, we assessed natural variation in the response of C. elegans towards
      a potential parasite, the soil bacterium Bacillus thuringiensis. Our results show
      that 10 isolates from across the world differ significantly in survival rate and
      infection level when confronted with a parasitic strain of B. thuringiensis.
      Furthermore, behavioural responses are identified as an important component of C.
      elegans defence, including evasion and possibly reduced ingestion of parasites.
      Again, the natural isolates show significant differences in these traits. In
      conclusion, worm defence is indicated to be complex and variable across space,
      implying that parasites play an important role in the ecology of this species.
      Based on these results, we expect C. elegans to be a promising model host for
      future analysis of the evolutionary dynamics of parasite-host interactions.

PMID- 15151148
TI  - A single nucleotide polymorphism map of the mitochondrial genome of the parasitic
      nematode Cooperia oncophora.
AB  - The 13,636 bp mitochondrial (mt) genome sequence of the trichostrongylid nematode
      Cooperia oncophora was determined. Like the mt genomes of other nematodes it is
      AT rich (76.75%) and cytidine is the least common nucleoside in the coding
      strand. There are 2 ribosomal RNA (rrn) genes, 22 transfer RNA (trn) genes and 12
      protein coding genes. The relatively short AT-rich region (304 bp) and the lack
      of a non-coding region between two of the NADH dehydrogenase genes, nad3 and
      nad5, makes the mt genome of C. oncophora one of the smallest known to date,
      having only 525 bp of non-coding regions in total. The majority of the C.
      oncophora protein encoded genes are predicted to end in an abbreviated stop codon
      like T or TA. In total, 426 single nucleotide polymorphisms (SNP) were mapped on
      the mt genome of C. oncophora, which is an average of 1 polymorphism per 32 bp.
      The most common SNPs in the mt genome of C. oncophora were G/A (59.2%) and C/T
      (28.4%) transitions. Synonymous substitutions (86.4%) were favoured over non
      synonymous substitutions. However, the degree of sequence conservation between
      individual protein genes of different parasitic nematode species did not always
      correspond to the relative number of non-synonymous SNPs. The mt genome sequence
      of C. oncophora presents the first mt genome of a member of the
      Trichostrongyloidea and will be of importance in refining phylogenetic
      relationships between nematodes. The, still limited, SNP map presented here
      provides a basis for obtaining insight into the genetic diversity present in the
      different protein coding genes, trn, rrn and non-coding regions. A more detailed
      study of the more variable regions will be of use in determining the population
      genetic structure of C. oncophora. Ultimately this knowledge will add to the
      understanding of the host-parasite relationship.

PMID- 15151150
TI  - Individual and combined effects of cadmium and 3,3',4,4',5-pentachlorobiphenyl
      (PCB 126) on the humoral immune response in European eel (Anguilla anguilla)
      experimentally infected with larvae of Anguillicola crassus (Nematoda).
AB  - The individual and combined effects of cadmium (Cd) and 3,3',4,4',5
      pentachlorobiphenyl (PCB 126) on the antibody response of fish against metazoan
      parasites were tested. Eels experimentally infected with the swim bladder
      nematode Anguillicola crassus were exposed to sublethal concentrations of Cd and
      PCB 126. Cd was added to the water resulting in an effective concentration of
      21.7 +/- 12.8 microg/l (mean +/- S.D.). PCB 126 was applied orally at a dose of
      approximately 100 ng PCB 126 per g body weight. At the end of the experiment, 76
      days post-infection (p.i.), eels were found to be infected with 2-3 worms.
      Immunoblot analyses revealed that the body wall of adult worms was the most
      suitable crude antigen, and was subsequently used for an ELISA to evaluate the
      immune response of A. anguilla under various conditions. A significant increase
      of Anguillicola-specific antibodies in the peripheral blood was first detected 61
      days p.i., indicating that it was not the invasive larvae but the adult worms
      which elicit the antibody response. The presence of Cd in the concentrations
      applied did not appear to modulate the production of antibodies. In contrast, the
      exposure to PCB 126 resulted in a complete suppression of the antibody response.
      A similar effect was also found for the combined exposure of the infected eels to
      Cd and PCB 126. A suppressed immune response, as demonstrated here, may be the
      reason why hosts exposed to environmental pollution became often much more easily
      infected than unexposed conspecifics.

PMID- 15151151
TI  - Echinococcus granulosus coproantigens: chromatographic fractionation and
      characterization.
AB  - Dogs infected with adult tapeworms of Echinococcus granulosus release antigens
      (coproantigens) in faeces which can be detected by a capture ELISA. Supernatants
      prepared from E. granulosus-infected dog faecal samples were fractionated by size
      exclusion fast protein liquid chromatography (FPLC) on a Superose-6 column.
      Coproantigen ELISA and Western blotting were used to demonstrate the
      immunoreactivity of eluted fractions. Two main FPLC peaks of antigenic activity
      were detected and designated as fraction F1 and fraction F2 with approximate
      relative molecular weights > 670 kDa, and in the range of 146 to 440 kDa
      respectively. These two antigenic fractions (F1 and F2) fractionated from
      infected dog faeces were heat stable and largely protease-insensitive, but were
      highly sensitive to sodium periodate treatment, which strongly suggested the
      involvement of carbohydrates. Capture IgG antibodies against E. granulosus
      proglottis somatic extracts, detected a molecule with an approximate molecular
      weight of 155 kDa in fraction F2 after immunoblotting. The 155 kDa antigen could
      be completely ablated by sodium periodate treatment, but not after protease or
      lipase treatment. A surface tegument preparation of adult E. granulosus tapeworms
      contained large amounts of antigen that corresponded in size range and
      antigenicity to that observed in the FPLC fraction F2. There was also a peak of
      antigenic activity at > 670 kDa corresponding to fraction F1 from a culture
      derived excretory-secretory (E-S) adult tapeworm preparation. The involvement of
      carbohydrate moieties in coproantigen activity present in the FPLC fractions F1
      and F2 from faecal supernatants of E. granulosus-infected dogs was confirmed by
      lectin-binding assays and exoglycosidase treatment, which showed that alpha-D
      mannose and/or alpha-D-glucose, beta-galactose and N-acetyl-beta-glucosamine
      residues were the most important carbohydrate components in putative
      coproantigens present in both fractions. N-acetyl-beta-glucosamine and sialic
      acid residues were also contained in coproantigen molecules present in fraction
      F2. These results suggested that coproantigens detected in faeces of E.
      granulosus-infected dogs are large molecular weight molecules that may be derived
      from the carbohydrate-rich surface glycocalyx of adult worms, and are shed,
      released or secreted during the life-span of the tapeworm.

PMID- 15151152
TI  - Effect of electronic ANR and conventional hearing protectors on vehicle backup
      alarm detection in noise.
AB  - An experiment was conducted wherein masked thresholds (using ascending method of
      limits) for a backup alarm were obtained in pink and red noise at 85 and 100 dBA
      for 12 participants immersed in a probability monitoring task and wearing a
      conventional passive hearing protection device (HPD, an earmuff or a foam
      earplug), an active noise reduction (ANR) headset, or no HPD at all (only in 85
      dBA noise). Results revealed statistically significant between-HPD differences in
      red noise (from 2.3 to 3.1 dB) and in the 100-dBA noise level (from 2.6 to 4.3
      dB). An additional finding, which corroborates other studies using different
      protocols, was that masked thresholds in 85-dBA noise were significantly lower
      (from 3.2 to 4.4 dB) for the occluded conditions (wearing an HPD) than for the
      open-ear (unoccluded) condition. This result refutes the belief among many normal
      hearing workers that the use of HPDs in relatively low levels of noise
      compromises their ability to hear necessary workplace sounds. Actual or potential
      applications of this research include (a) the selection of appropriate HPDs for
      low-frequency-biased noise exposures wherein signal detection is important and
      (b) gaining insight into the appropriateness of ANR-based HPDs for certain
      industrial noise environments.

PMID- 15151154
TI  - The use of flight progress strips while working live traffic: frequencies,
      importance, and perceived benefits.
AB  - The Federal Aviation Administration's effort to automate air traffic control
      (ATC) requires that the functionality provided today be captured in future
      systems. We report the first quantitative naturalistic observation of paper
      flight progress strip interactions during operational use. Strip use was similar
      in a variety of situations, but some uses varied as a function of altitude,
      staffing, or the cooperative style used by controller teams. Design of automation
      should proceed by prioritizing changes based on frequency of use and importance
      and should ensure that an effective method of interacting with flight information
      is incorporated. In addition to applied relevance to the ATC domain, the results
      touch on several theoretical concerns relevant to dynamic environments. Actual
      and potential applications of this research include the establishment of a
      database of strip activity and an arsenal of information valuable to system
      designers.

PMID- 15151153
TI  - Linguistic and location effects in compliance with pesticide warning labels for
      amateur and professional users.
AB  - Three studies explored amateur and professional users' compliance with pesticide
      warning labels. Professionals were classified as people working in a profession
      in which the use of pesticides is a necessary part of their job. Amateurs used
      pesticides only in their leisure time. The first study showed that the wording
      used affected perception of the appropriateness of hazard statements, one of the
      most effective variations being the use of the personal pronoun (statements
      beginning "You should..."). The location of warning information was also found to
      affect actual compliance: Compliance increased when warning information was
      presented in the directions for use section. A supplemental directive increased
      compliance only for professional users. In a final study, "best-case" and "worst
      case" linguistic variations were combined with best-case and worst-case locations
      for safety information. Instruction statements using the personal pronoun and
      presented in the directions for use section resulted in the highest levels of
      compliance. The differences in compliance between amateur and professional users
      are interpreted within the framework of Rasmussen's (1986) distinction among
      skill-, rule-, and knowledge-based behavior. Actual or potential applications of
      this research include the design of warning labels and safety information.

PMID- 15151155
TI  - Trust in automation: designing for appropriate reliance.
AB  - Automation is often problematic because people fail to rely upon it
      appropriately. Because people respond to technology socially, trust influences
      reliance on automation. In particular, trust guides reliance when complexity and
      unanticipated situations make a complete understanding of the automation
      impractical. This review considers trust from the organizational, sociological,
      interpersonal, psychological, and neurological perspectives. It considers how the
      context, automation characteristics, and cognitive processes affect the
      appropriateness of trust. The context in which the automation is used influences
      automation performance and provides a goal-oriented perspective to assess
      automation characteristics along a dimension of attributional abstraction. These
      characteristics can influence trust through analytic, analogical, and affective
      processes. The challenges of extrapolating the concept of trust in people to
      trust in automation are discussed. A conceptual model integrates research
      regarding trust in automation and describes the dynamics of trust, the role of
      context, and the influence of display characteristics. Actual or potential
      applications of this research include improved designs of systems that require
      people to manage imperfect automation.

PMID- 15151157
TI  - Pilot ability to anticipate the consequences of flight actions as a function of
      expertise.
AB  - The study offers insights into pilot ability to anticipate consequences of
      actions and how this ability changes with experience. Novice and expert pilots
      completed trials in which 3 screens depicted a control movement (or control
      movements), a cockpit flight situation, or a change in flight situation. Changes
      depicted in the 3rd screen of each trial were consistent, inconsistent with the
      mental model of the effect of the control movement or movements, or inconsistent
      with the application of the control movement(s) to the current flight situation.
      Pilots indicated whether the depicted change was inconsistent or consistent with
      their expectations, and accuracy of consistency judgments was greater for mental
      model than for situation-model inconsistent statements. Experts are more accurate
      than novices, particularly for trials that involve multiple, meaningfully related
      control movements. Expert ability to organize information into meaningful units
      appears to facilitate future flight state projections, and projection failures
      appear to result from situation- rather than mental-model failures. Actual or
      potential applications of this research include analysis of flight situation
      awareness and flight performance errors.

PMID- 15151158
TI  - Effects of organizational scheme and labeling on task performance in product
      centered and user-centered retail Web sites.
AB  - As companies increase the quantity of information they provide through their Web
      sites, it is critical that content is structured with an appropriate
      architecture. However, resource constraints often limit the ability of companies
      to apply all Web design principles completely. This study quantifies the effects
      of two major information architecture principles in a controlled study that
      isolates the incremental effects of organizational scheme and labeling on user
      performance and satisfaction. Sixty participants with a wide range of Internet
      and on-line shopping experience were recruited to complete a series of shopping
      tasks on a prototype retail shopping Web site. User-centered labels provided a
      significant benefit in performance and satisfaction over labels obtained through
      company-centered methods. User-centered organization did not result in improved
      performance except when the label quality was poor. Significant interactions
      suggest specific guidelines for allocating resources in Web site design.
      Applications of this research include the design of Web sites for any commercial
      application, particularly E-commerce.

PMID- 15151156
TI  - Influence of fatigue in neuromuscular control of spinal stability.
AB  - Lifting-induced fatigue may influence neuromuscular control of spinal stability.
      Stability is primarily controlled by muscle recruitment, active muscle stiffness,
      and reflex response. Fatigue has been observed to affect each of these
      neuromuscular parameters and may therefore affect spinal stability. A
      biomechanical model of spinal stability was implemented to evaluate the effects
      of fatigue on spinal stability. The model included a 6-degree-of-freedom
      representation of the spine controlled by 12 deformable muscles from which muscle
      recruitment was determined to simultaneously achieve equilibrium and stability.
      Fatigue-induced reduction in active muscle stiffness necessitated increased
      antagonistic cocontraction to maintain stability resulting in increased spinal
      compression with fatigue. Fatigue-induced reduction in force-generating capacity
      limited the feasible set of muscle recruitment patterns, thereby restricting the
      estimated stability of the spine. Electromyographic and trunk kinematics from 21
      healthy participants were recorded during sudden-load trials in fatigued and
      unfatigued states. Empirical data supported the model predictions, demonstrating
      increased antagonistic cocontraction during fatigued exertions. Results suggest
      that biomechanical factors including spinal load and stability should be
      considered when performing ergonomic assessments of fatiguing lifting tasks.
      Potential applications of this research include a biomechanical tool for the
      design of administrative ergonomic controls in manual materials handling
      industries.

PMID- 15151159
TI  - Detection of temporal delays in visual-haptic interfaces.
AB  - This paper addresses the question of how large the temporal delay between a
      visual and a haptic stimulus may be such that the stimuli are still perceived as
      being synchronous. Participants had to judge whether the moment at which a
      graphical object collided with a virtual wall occurred simultaneously with the
      moment at which a force was felt through a force feedback joystick. Participants
      either moved the joystick to drive the object (active touch) or held the joystick
      in a steady position while the object moved by itself (passive touch).
      Participants were found to be very sensitive to visual-haptic time delays.
      Sensitivity was higher for passive touch than for active touch. The minimum delay
      at which participants judged the stimuli as asynchronous was on average 45 ms.
      The delay at which the proportion of synchronous judgments reached a maximum was
      on average close to zero. The results indicate that the temporal accuracy of
      visual-haptic interfaces has to meet stringent requirements in order to optimize
      the overall realism that users experience. Actual or potential applications of
      this research include teleoperation, medical training, computer-aided-design, and
      scientific visualization.

PMID- 15151160
TI  - Foveal task complexity and visual funneling.
AB  - The current study was designed to examine whether increasing foveal task
      complexity would cause the functional field to shrink as a result of a visual
      funneling effect. Using 8 male participants, the study examined whether the
      effects of foveal task complexity on peripheral performance was most pronounced
      at the far periphery. The response time to an addition task using foveal vision
      tended to increase with the increase of the visual angle. The percentage correct,
      however, did not differ among 3 levels of task complexity or among 4 levels of
      visual angle. The miss rate in the peripheral vision task tended to increase with
      the increase in not only the complexity of the foveal task but also the visual
      angle. This is indicative of visual funneling. However, greater funneling was not
      necessarily observed for response time. In this study, response time was not a
      sensitive measure of visual funneling. Actual or potential applications of this
      research include safe driving and other vigilance tasks.

PMID- 15151161
TI  - "Conflicting" motion cues to the visual and vestibular self-motion systems around
      0.06 Hz evoke simulator sickness.
AB  - The basic question this research addressed was, how does simulator sickness vary
      with simulated motion frequency? Participants were 11 women and 19 men, 20 to 63
      years of age. A visual self-motion frequency response curve was determined using
      a Chattecx posture platform with a VR4 head-mounted display (HMD) or a back
      projected dome. That curve and one for vestibular self-motion specify a frequency
      range in which vestibular and visual motion stimuli could produce conflicting
      self-motion cues. Using a rotating chair and the HMD, a third experiment
      supported (p < .01) the hypothesis that conflicting cues at the frequency of
      maximum "crossover" between the curves (about 0.06 Hz) would be more likely to
      evoke simulator sickness than would conflicting cues at a higher frequency.
      Actual or potential applications of this work include a preliminary design
      guidance curve that indicates the frequency range of simulated motion that is
      likely to evoke simulator or virtual reality sickness; for simulators intended to
      operate in this frequency range, appropriate simulator sickness interventions
      should be considered during the design process.

PMID- 15151162
TI  - Temporal separation and self-rating of alertness as indicators of driver fatigue
      in commercial motor vehicle operators.
AB  - This on-road field investigation employed, for the first time, a completely
      automated trigger-based data collection system capable of evaluating driver
      performance in an extended-duration real-world commercial motor vehicle
      environment. The study examined the use of self-assessment of fatigue (Karolinska
      Sleepiness Scale) and temporal separation (minimum time to collision, minimum
      headway, and mean headway) as indicators of driver fatigue. Without exception,
      the correlation analyses for both the self-rating of alertness and temporal
      separation yielded models low in associative ability; neither metric was found to
      be a valid indicator of driver fatigue. In addition, based upon the data
      collected for this research, preliminary evidence suggests that driver fatigue
      onset within a real-world driving environment does not appear to follow the
      standard progression of events associated with the onset of fatigue within a
      simulated driving environment. Application of this research includes the
      development of an on-board driver performance/fatigue monitoring system that
      could potentially assist drivers in identifying the onset of fatigue.

PMID- 15151163
TI  - Educational interventions successfully reduce pedestrians' overestimates of their
      own nighttime visibility.
AB  - Pedestrians dramatically overestimate their own visibility at night. This is
      likely to result in pedestrians unknowingly engaging in dangerous behavior. To
      determine the extent to which pedestrians' estimates of their own visibility are
      influenced by educational interventions, clothing reflectance, and headlamp beam
      setting, participants in 2 experiments estimated their own nighttime visibility
      by walking toward a stationary car to the point where they believed they were
      just recognizable as a pedestrian. In the first experiment 48 university students
      were tested and in the second experiment 9 high-school driver education students
      were tested. Overall, participants failed to appreciate the benefits of
      reflective clothing and of high-beam illumination. However, the participants in
      Experiment 1 who had heard a relevant lecture several weeks earlier gave
      estimates that were 10% shorter than did a control group. Participants in
      Experiment 2 heard a more focused and graphic-intensive lecture and gave
      estimates that were 56% shorter than did a control group. Potential applications
      of this research include increasing pedestrian safety by designing and
      implementing research-based public education campaigns aimed at reducing
      pedestrians' overestimates of their own nighttime visibility.

PMID- 15151164
TI  - The role of positron emission tomography in the discovery and development of new
      drugs; as studied in laboratory animals.
AB  - Drug discovery and development is time consuming and a costly procedure. The
      challenges for the pharmaceutical industry range from the evaluation of potential
      new drug candidates, the determination of drug pharmacokinetics/pharmacodynamics,
      the measurement of receptor occupancy as a determinant of drug efficacy, and the
      pharmacological characterisation of mechanisms of action. Positron emission
      tomography (PET) is a powerful quantitative imaging technique for looking at
      biochemical pathways, molecular interactions, drug pharmacokinetics and
      pharmacodynamics. Recent advances in emission tomography, particularly the
      development of small animal PET scanners, image reconstruction and animal models
      of disease have led to the development of extremely sensitive and specific tools
      for imaging biochemical processes in vivo, therefore representing a new means of
      providing information for drug development and evaluation. Many human genes have
      a related mouse gene, allowing mice to be used as a platform for mimicking human
      disease, using knock-out and knock-in gene technology. Consequently PET imaging
      of rodents is emerging as a cost effective means of screening new pharmaceuticals
      and decreasing the time required for new drug development.

PMID- 15151166
TI  - Absorption, distribution, metabolism and excretion of the cholecystokinin-1
      antagonist dexloxiglumide in the dog.
AB  - Single oral doses of 14C-dexloxiglumide were rapidly and extensively absorbed in
      dogs and also eliminated rapidly with a short half-life. Following single
      intravenous doses, dexloxiglumide was characterised as a drug having a high
      clearance (30.7 and 27.0 ml/min/kg in males and females respectively), a low
      volume of distribution (Vss, 0.34 and 0.27 L/kg in males and females
      respectively) and a moderate systemic availability (about 33%). It was
      extensively bound to plasma proteins (89%). Dexloxiglumide is mainly cleared by
      the liver. Its renal clearance was minor. In only the kidney, liver and
      gastrointestinal tract, were concentrations of 14C generally greater than those
      in plasma. 14C concentrations generally peaked at 0.25h and declined rapidly
      during 24h being present only in a few tissues (such as the kidney, liver and
      gastrointestinal tract) at 24h. Single intravenous or oral doses were mainly
      excreted in the faeces (77-89%), mostly during 24h. Urine contained up to 7.5%
      dose. Mean recoveries during 7 days ranged between 93-97%. Biliary excretion of
      14C was prominent (64% dose during 24h) in the disposition of 14C which was
      probably also subjected to some limited enterohepatic circulation. Unchanged
      dexloxiglumide was the major component in plasma. Urine and faeces contained
      several 14C-components amongst which unchanged dexloxiglumide was the most
      important (eg. about 55% dose in faeces). LC-MS/MS of urine and bile extracts
      showed that dexloxiglumide was metabolised mainly by O-demethylation and by
      conjugation with glucuronic acid.

PMID- 15151165
TI  - Pharmacokinetics of YM466, a new factor Xa inhibitor, in rats and dogs.
AB  - The pharmacokinetics of YM466, a selective inhibitor for factor Xa, was
      investigated after single intravenous and oral dosing to rats and dogs. After
      i.v. dosing, plasma YM466 concentration declined in a bi-phasic manner with a
      terminal elimination half-life of 1.4 h in rats and 0.8 h in dogs. Total plasma
      clearance values were 884 and 1212 ml/h/kg in rats and dogs, respectively. After
      oral dosing, plasma YM466 concentrations reached maximum within 2 h and increased
      in a dose-proportional manner in rats while increase was nonlinear in dogs. The
      absolute bioavailability of YM466 was 2.7-4.5% in rats, almost constant
      regardless of the dose levels investigated, while it was 6.9-24.6% in dogs,
      indicating nonlinear pharmacokinetics. The plasma protein binding of YM466 was
      54.7-56.5% in rats and 45.2-49.0% in dogs and almost constant regardless of the
      concentration. No metabolism of YM466 was observed in an in vitro liver microsome
      study. These findings suggest that the low bioavailability of YM466 is
      attributable to the poor absorption not to the extensive metabolism.

PMID- 15151167
TI  - Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics
      of acetaminophen in human volunteers.
AB  - Acetaminophen, a common antipyretic-analgesic OTC drug is often administered
      orally anytime of the day with water or beverages irrespective of possible
      interactions. Zobo drink, is a sweetened water extract of the dried calyx of
      Hibiscus Sabdariffa. This work is designed to investigate the effect of zobo
      drink on an oral dose of acetaminophen. Six healthy male volunteers, ages 28.50
      +/- 1.76 years, weighing 62.67 +/- 1.67kg participated in the study. The study
      was carried out in two phases. In the first phases an oral dose of acetaminophen
      (1g) was administered to the volunteers and in the second phases, zobo drink was
      ingested by the volunteers 1.30 h prior the administration of acetaminophen (1g).
      Acetaminophen concentration in plasma was determined using a validated
      spectrophotometric method. Pharmacokinetic values obtained were found to be in
      similar ranges as those previously reported. The absorption parameters t1/2a, Ka,
      Tmax, Cmax and AUC0-alpha showed no statistically significant changes (p>0.05)
      after the administration of zobo. There were however statistically significant
      changes (p<0.05) in Kbeta and t1/2beta of acetaminophen when administered after
      the zobo drink. This also resulted in 11.69% increase in ClT.

PMID- 15151169
TI  - Effect of erythrocytes on the hepatic distribution kinetics of antipyrine.
AB  - The role of erythrocyte on the hepatic distribution kinetics of antipyrine was
      investigated in the in situ isolated perfused rat liver. Perfusion experiments
      were conducted using Krebs-bicarbonate buffer delivered via the portal vein in a
      single pass mode at a total flow rate of 15 ml/min. A bolus dose of antipyrine
      was administered in the presence and absence of erythrocytes. Almost identical
      moment analysis results (without erythrocytes mean transit time, MTT: 23 s;
      volume of distribution, VH: 0.57 ml/g liver and with erythrocytes, MTT: 24 s; VH:
      0.60 ml/g liver) and superimposable unimodal effluent curves were obtained in the
      presence and absence of erythrocytes indicates that distribution kinetics of
      antipyrine within the liver is not affected by erythrocytes.

PMID- 15151168
TI  - Stimulation of lipid peroxidation and impairment of glutathione-dependent defense
      system in Wistar rats treated with cryptopine, a rare non-narcotic opium
      alkaloid.
AB  - The present study was designed to evaluate the effect of repeated oral
      administration of cryptopine at differential dosing regimens (50, 100, 150, 200
      mg/kg bwt) in vivo on lipid peroxide measures, glutathione levels (GSH) and
      activity of glutathione S-transferase (GST) and glutathione reductase (GR) in the
      liver, spleen, kidney and lung of Male Wistar rats after a 5 day treatment
      period. In all the tissues examined, we observed an increase in lipid
      peroxidation and a decline in glutathione content and activity of glutathione S
      transferase and glutathione reductase in a dose-dependent manner. The decrease in
      GSH content did not definitively correlate with a concomitant increase of lipid
      peroxidation in all the tissues. Our results ensemble that the enhancement of
      lipid peroxidation in the tissues investigated is a consequence of depletion of
      glutathione to certain critical levels and impairment of the glutathione
      dependent enzyme systems viz. GST and GR. Our study potentiates that decreased
      levels of GSH may lead to lipid peroxidation, one of the key events in cellular
      damage. The inhibition of GST also suggests that the detoxification of the
      alkaloid could be suppressed following acute exposures. Conclusively, it appears
      that cryptopine in vivo disturbs the cellular defense system, so that it tips in
      the direction of autoxidative lipid peroxidation, producing cytotoxicity.

PMID- 15151170
TI  - Multiplicative dependence of the first order rate constant and its impact on
      clinical pharmacokinetics and bioequivalence.
AB  - The purpose of the study was to investigate the factors upon which the first
      order rate constant depends in order to assess the impact on the body-drug
      concentration when it changes throughout a treatment. A reasoning for linking the
      first order rate constants with several factors in a multiplicative way was
      proposed out taking into account kinetic and thermodynamic aspects. A multi
      compartment model for drug disposition was analyzed and compartment mean drug
      concentrations at steady state were obtained as a function of the model kinetic
      constants. At the moment, only four factors were identified as responsible for
      the actual rate constant value. Apart from an intrinsic kinetic constant, they
      are the inverse of compartment volume, the transfer surface area, the fraction of
      mass able to be transferred, and the fraction of mass that effectively can be
      transferred. In clinical practice some of these factors might change throughout
      time (because of chronophysiological rhythms or drug availability at the action
      sites) and consequently, an inconstant extra-plasma/plasma drug concentration
      ratio could be obtained. In conclusion, therapeutic response prediction for a
      treatment does not upon plasma drug concentration monitoring. Equivalence in
      plasma drug exposure should not mean therapeutic equivalence, because differences
      in the rate and in the extent between test and reference products may induce a
      change in the action site/plasma drug concentration ratio.

PMID- 15151171
TI  - Phenobarbital N-glucosylation by human liver microsomes.
AB  - Glucosylation of xenobiotics in mammals has been observed for a limited number of
      drugs. Generally, these glucoside conjugates are detected as urinary excretion
      products with limited information on their formation. An in vitro assay is
      described for measuring the formation of the phenobarbital N-glucoside
      diasteriomers ((5R)-PBG, (5S)-PBG) using human liver microsomes. Human livers (n
      = 18) were screened for their ability to N-glucosylate PB. Cell viability, period
      of liver storage, prior drug exposure, serum bilirubin levels, age, sex and
      ethnicity did not appear to influence the specific activities associated with the
      formation of the PB N-glucosides. The average rate of formation for both PB N
      glucoside was 1.42 +/- 1.04 (range 0.11-4.64) picomole/min/mg-protein with an
      (5S)-PBG/(5R)-PBG ratio of 6.75 +/- 1.34. The apparent kinetic constants, Km and
      Vmax, for PB N-glucosylation for eight of the livers ranged from 0.61-20.8 mM and
      2.41-6.29 picomole/min/mg-protein, respectively. The apparent Vmax/Km ratio for
      PB exhibited a greater than 20 fold variation in the ability of the microsomes to
      form the PB N-glucosides. It would appear that the formation of these barbiturate
      N-glucoside conjugates in vitro are consistent with the amount of barbiturate N
      glucosides formed and excreted in the urine in prior drug disposition studies.

PMID- 15151172
TI  - Assessment of the sustained release properties of a new oral formulation of
      trimetazidine in pigs and dogs and confirmation in healthy human volunteers.
AB  - The pharmacokinetics of immediate (IR) and modified release (MR) trimetazidine
      (TMZ) in dogs and pigs, have been compared under single dose conditions, then
      predicted at steady-state under conditions mimicking an actual human
      pharmacokinetic study. In both animal species, the MR tablet has demonstrated
      sustained release properties, as assessed by delayed time to peak and increased
      mean absorption times. Multiple dose simulations in dogs revealed a delayed time
      to peak (3.0 vs. 1.0 h), a decrease in peak plasma concentration (544 vs. 659
      microg/L), an increase in trough concentrations (115 vs. 63 microg/L), a decrease
      in peak-trough fluctuation (141 vs. 193%), and an increase in plateau time (5.5
      vs. 4.9 h). Qualitatively similar changes were simulated in pigs. These
      properties have then been verified in humans where a TMZ MR 35 mg b.i.d regimen
      did provide similar total exposure, increased plateau time (11 vs. 4 h),
      decreased peak-trough fluctuation (86 vs. 121%), a 31% increase in trough
      concentrations, and no increase in inter-individual variability as compared to a
      TMZ IR 20 mg t.i.d. regimen. Furthermore, the TMZ MR 35 mg b.i.d. regimen is
      likely to result in improved patient compliance and better patient anti-ischemic
      protection in the early morning.

PMID- 15151173
TI  - An extremely strange observation?

PMID- 15151174
TI  - Structural changes in the dendritic spines of pyramidal neurons in layer III of
      the sensorimotor cortex of the rat cerebral cortex in the late post-ischemic
      period.

PMID- 15151175
TI  - The role of the basal ganglia in organizing behavior.

PMID- 15151176
TI  - Behavior-reactive neuron populations in the monkey neostriatum.
AB  - Comparative analysis of neuron activity in the monkey putamen during multistep
      behavior showed that putamen neurons are active during all the animal's
      behavioral actions. The difference between the number of active neurons at a
      given step of the behavior as compared with the preceding step was found to be
      significantly smaller than the number of neurons reorganizing their activity at
      this step. Reorganization of neuron activity in the putamen is regarded as a
      reflection of the efferent code controlling the behavior, while the extent of
      reorganization is regarded as a measure of the change in this code in association
      with the organization of a sequential behavioral action. Changes in the numbers
      of active neurons at different stage of behavior and reorganization of their
      activity occurred independently of each other. This may be associated with the
      two afferent systems of the striatum: that ascending from the brainstem and the
      corticofugal, which carries differential information to the neural network of the
      striatum from various parts of the cortex.

PMID- 15151177
TI  - The differentiating activity of monkey putamen neurons during performance of
      alternative spatial selection.
AB  - Spike activity was recorded from three zones of the putamen in monkeys trained to
      bimanual operant activity during performance of an alternative spatial selection
      task. Neuron responses were analyzed using the following criteria: a)
      differentiation of the side providing reinforcement (differentiating/non
      differentiating responses); b) response duration (tonic/phasic); c) response
      laterality (contralateral/ipsilateral hemispheres); d) baseline activity
      frequency. The differentiating activity of cells was found to show the closest
      correlation with behavioral aspects of the program, particularly the tonic part
      and, even more so, contralateral tonic responses. It is suggested that
      differentiating activity, as opposed to non-differentiating activity, is less a
      reflection of the morphological and neurochemical characteristics of the neural
      elements of the putamen than of their functional homogeneity in relation to
      external determinants of behavior.

PMID- 15151178
TI  - Sequential rearrangements of the ensemble activity of putamen neurons in the
      monkey brain as a correlate of continuous behavior.
AB  - Simultaneous recordings were made of the spike activity of groups of 6-7 neurons
      in the putamen in two monkeys (Macaca nemestrina and Macaca mulatta) during
      performance of alternative spatial selection. Discriminant analysis was used to
      evaluate the magnitude of rearrangements in spike activity in groups of neurons
      during transitions from each step of the behavioral program to the next, along
      with the degree of differences in reactivity mosaics formed at each step in
      different versions of task execution. Rearrangements in spike activity were noted
      at all steps of the program. The dynamics of rearrangements on selection of the
      right and left feeders were different, leading to the appearance of significant
      differences in the reactivity mosaics at the decision-taking and reinforcement
      receiving steps. The rearrangements preceding voluntary movement of one hand were
      more marked in the contralateral hemisphere. During performance of movements, the
      volume of rearrangements could increase, though differences in rearrangements
      accompanying movements of the right and left hands decreased. On receipt of
      reinforcement, rearrangements were greater when the animals selected a specified
      feeder (the left feeder) independently of which hemisphere was recorded.

PMID- 15151179
TI  - Reflection of the spatial characteristics of an acoustic signal in the activity
      of caudate nucleus neurons.
AB  - Studies were performed on five dogs. Chronic experimental conditions were used to
      study the responses of individual neurons in the caudate nucleus to the spatial
      characteristics of an acoustic signal. The results showed that 92% of sound
      stimulus-responsive neurons in the head of the caudate nucleus in dogs generated
      asymmetrical responses to contra- and ipsilateral monaural stimulation, with
      contralateral stimulation being more effective. In 50% of caudate nucleus
      neurons, simultaneous stimulation of both sound inputs was more effective than
      contralateral stimulation. A total of 77% of sound-responsive caudate neurons
      demonstrated sensitivity to changes in the magnitude and sign of the interaural
      delay.

PMID- 15151180
TI  - Analysis of the morphological substrate for information processing in the
      striatum based on the organizational characteristics of its afferent projections.
AB  - Retrograde axonal transport of markers was used to study the afferent projections
      arising from functionally diverse cortical and subcortical structures and running
      to various segments of the caudate nucleus, nucleus accumbens, and putamen of the
      dog brain. The characteristics of the spatial organization of these projections
      were used to analyze the morphological aspects of the segregated and convergent
      conduction and processing of information in the striatum which underlie striatal
      function.

PMID- 15151181
TI  - Analysis of the morphological substrate for information processing in the
      pallidal nuclear complex of the dog brain in terms of the organizational
      characteristics of its afferent projections.
AB  - Axonal transport of retrograde markers was used to study the distribution of the
      afferent projections of the nuclei of the pallidal complex (the globus pallidus,
      the entopeduncular nucleus, and the ventral pallidum) from functionally diverse
      cortical and subcortical structures (cortical fields, substantia nigra, ventral
      tegmental field, and thalamus) in the dog brain. The results were used to analyze
      the morphological aspects both of the functional heterogeneity of the pallidum
      and integrative information processing, which underlie the mechanisms of adaptive
      behavior.

PMID- 15151182
TI  - Neurons of the basal ganglia of the human brain (striatum and basolateral
      amygdala) expressing the enzyme NADPH-d.
AB  - Types of NADPH-d+ neurons (Vincent et al., 1983) were identified in the striatum
      and basolateral nuclei of the amygdala; striocortical neurons were detected in
      the striatum using the DiI marker (Belichenko and Dahlstrom, 1995). NADPH-d+
      cells were numerous. Staining of these cells and all their processes, along with
      our previous studies of the neurons in these formations in the human brain using
      the Golgi method, allowed us to identify their shapes and identify them as
      sparsely or extensively branched cells. The main efferent neurons of the striatum
      and basolateral amygdala (extensively branched medium spiny cells and bushy spiny
      cells respectively) and their extensively branched interneurons did not contain
      NADPH-d. Efferent NADPH-d+ neurons included reticular, sparsely branched cells
      with long dendrites, which were the most numerous cells in both formations, as
      well as occasional large multipolar branched neurons; the striatum also contained
      numerous sparsely branched short-dendrite cells (a neuron type most represented
      in the brainstem and especially the reticular formation). Projections of
      reticular cells from the striatum to the cortex were demonstrated. NADPH-d+
      interneurons were sparsely branched: in the striatum, these were slender, long
      dendrite, bipolar cells (numerous), ordinary bipolar cells, twisted and large
      dendrite-poor cells; the amygdala contained the same bipolar cells along with
      radial neurons. Thus, NADPH-d+ neurons in these formations were more ancient,
      i.e., structurally less complex, cell types.

PMID- 15151183
TI  - The role of the substantia nigra in cognitive activity in cats.
AB  - The role of the substantia nigra in cognitive processes of different levels of
      complexity was studied using an original method. Neurosurgical or neurochemical
      exclusion of the substantia nigra in cats led to significant impairment of
      conditioned reflex activity, generalization and abstraction processes; these
      recovered with pharmacological treatment directed to the dopaminergic system,
      with partial recovery after treatment directed to the GABAergic and cholinergic
      systems. Treatment directed to the serotoninergic system was ineffective.

PMID- 15151184
TI  - Motor behavior in rats after separate and combined administration of GABAergic
      agents into the neostriatum.
AB  - Chronic experiments were performed on rats to study the main inhibitory
      transmitter system of the neostriatum--the GABAergic system--in the regulation of
      normal and pathological motor behavior. Studies addressed the effects of separate
      and combined administration of GABA (45 microg) and A-type receptor antagonists,
      i.e., picrotoxin (1 microg) and bicuculline (5 microg), into the neostriatum on
      the performance by rats of spontaneous (including pathological) and conditioned
      reflex motor behavior (active avoidance reflex in a shuttle box). Agents were
      injected in a volume of 1 microl daily for three weeks; control animals received
      physiological saline. Activation of the GABAergic system of the neostriatum had
      no significant effect on behavior. Conditioned reflex avoidance behavior was
      impaired throughout the period of bicuculline administration (there was no
      significant change in spontaneous behavior); this recovered after the course of
      microinjections finished. Picrotoxin produced smaller negative effects on
      performance of the reflex, though rats showed clear imperative movements in the
      form of choreomyoclonic hyperkinesia. Simultaneous administration of picrotoxin
      and GABA into the neostriatum produced less hyperkinesia; administration of
      picrotoxin and bicuculline altered the nature of hyperkinesia. The importance of
      the GABAergic system for the antihyperkinetic activity of the basal ganglia is
      discussed, and it is suggested that the GABA-A subsystem is of critical
      importance in these functions.

PMID- 15151185
TI  - Characteristics of the actions of neurotensin on motor reactions in rats in
      response to positive and negative conditioned signals.
AB  - This study addressed the effects of microinjections of neurotensin into the
      caudate nucleus and substantia nigra on the performance of motor reactions in
      response to positive and negative conditioned signals, as well as the post
      effects of microinjections in subsequent experiments. Neurotensin had positive
      effects on the extinction of non-reinforced motor reactions. Neurotensin had no
      effect on the number of motor responses to the non-reinforced signal, though the
      number decreased in subsequent experiments. There was an increase in the latent
      period of responses as compared with controls. The effect of neurotensin at the
      level of the caudate nucleus was more marked than that at the level of the
      substantia nigra. Neurotensin microinjections had no marked effect on performance
      of conditioned responses to positive signals. The behavioral effects of
      neurotensin are associated with normalization of the interactions of the brain's
      monoaminergic systems. It is suggested that the positive actions of neurotensin
      on extinction of motor responses to negative signals result from the formation of
      a contextual conditioned emotional state in the animals, this facilitating
      optimization of conditioned reflex activity.

PMID- 15151186
TI  - Family involvement following institutionalization: modeling nursing home visits
      over time.
AB  - Gerontological research has emphasized family members' continued involvement in
      the lives of loved ones following institutionalization. However, many of these
      studies are cross-sectional in design and do not ascertain how family members'
      visits change over time. The present study utilized a growth curve analysis to
      examine preplacement and postplacement predictors of nursing home visits over a
      two-year period among a sample of 65 caregivers of dementia patients.
      Intraindividual patterns of change suggested considerable heterogeneity in family
      visits. Several variables were also significantly predictive (p < .05) of change
      in nursing home visits. Spousal caregivers were more likely to report increased
      visits. Care recipients with greater cognitive impairment following
      institutionalization experienced increased visits. Caregivers who perceived
      respect and support from their social network following institutionalization also
      reported increased visits over the two-year study period. Caregivers who engaged
      in socially restorative activities after institutionalization reported decreases
      in visits. The findings provide a more refined understanding of the long-term
      involvement process following institutionalization.

PMID- 15151187
TI  - Investigating moderator hypotheses in aging research: statistical,
      methodological, and conceptual difficulties with comparing separate regressions.
AB  - Many topics in aging research address questions about group differences in
      prediction. Such questions can be viewed in terms of interaction or moderator
      effects, and use of appropriate methods to test these hypotheses are necessary to
      arrive at accurate conclusions about age differences. This article discusses the
      conceptual, methodological, and statistical problems in one approach to
      investigating moderator hypotheses. The subgroup regression approach, in which
      separate regression analyses are conducted in two or more groups, is widely used
      in aging research to examine group differences in prediction, but the approach
      can lead to erroneous conclusions. The moderated regression approach, involving
      the test of a product term, is described and recommended as an a alternative
      approach. The question of whether social support has greater beneficial effects
      for younger or older adults is investigated in a study of 287 recently-bereaved
      adults ranging in age from 20 to 91. Using the subgroup approach, findings
      indicated that social support significantly predicted depressive symptoms among
      younger adults and did not significantly predict depressive symptoms among older
      adults. The moderated regression analysis, however, indicated no significant age
      differences in the effect of social support. These results clearly illustrate
      that the analysis strategy researchers choose may have important bearing on
      theory in aging research such as conclusions regarding the role of social support
      across the life span.

PMID- 15151188
TI  - Older adults' attitudes, concerns, and support for environmental issues in the
      "New West".
AB  - The natural environment has been a missing topic from education and public policy
      forums concerning an aging society. This study examines demographic trends and
      several socio-demographic influences on attitudes, concerns, and active support
      for environmental issues among older adults in a retirement "hot spot" in the New
      West. A sample of 394 older adults in southwestern Utah was obtained from
      questionnaires mailed to those randomly selected from a larger dataset, and
      through hand-distributed questionnaires at selected RV parks. We found a high
      degree of variability among respondents in regard to environmental attitudes and
      concerns. Despite a personal attitudinal desire to protect the environment, most
      older adults did not want to become involved in protective actions for the
      environment. We found that residency status and religious affiliation emerged as
      the strongest relationships with measures of attitudes and concerns, and
      willingness to support the environment. The most influential factors associated
      with willingness to take action in support of the environment were having higher
      levels of active/social concerns, and higher levels of awareness of environmental
      consequences. The New West is one of the fastest-growing areas for demographic
      aging, and the opinions and actions of older adults will play a significant role
      in the stewardship and sustainability of natural resources, particularly in
      retirement hot spots.

PMID- 15151189
TI  - Strengths and satisfaction across the adult lifespan.
AB  - Positive psychology has recently developed a classification of human strengths
      (Peterson & Seligman, in press). We aimed to evaluate these strengths by
      investigating the strengths and life satisfaction in three adult samples
      recruited from the community (young adult, middle-aged, and older adult), as well
      as in the surviving men of the Grant study of Harvard graduates. In general,
      older adults had higher levels of interpersonal and self-regulatory strengths,
      whereas younger adults reported higher levels of strengths related to exploring
      the world. Grant study men tended to report lower strength levels than older
      adults from the community. Among the young adults, only hope significantly
      predicted life satisfaction, whereas among the middle-aged individuals, the
      capacity for loving relationships was the only predictor. Among community
      dwelling older adults, hope, citizenship, and loving relationships all positively
      and uniquely predicted life satisfaction, compared with loving relationships and
      appreciation of beauty in the Grant sample.

PMID- 15151190
TI  - Grammatical performance of children with language disorder on structured
      elicitation and narrative tasks.
AB  - The primary objective was to compare the grammatical output of children with
      language disorders on different tasks. Sixty-five children with language
      disorders, aged six to eleven, completed the syntactic formulation (elicitation)
      and narrative subtests from the Assessment of Comprehension and Expression 6-11
      (Adams et al. 2001). Grammatical variables were computed for the narrative data
      and their relationship with the syntactic formulation subtest score examined. The
      use of ten specific constructions was compared in the two contexts. The syntactic
      formulation score correlated highly with narrative grammatical variables.
      However, for seven of the ten constructions, the elicitation task was more likely
      than the narrative to yield specific target structures. Structured elicitation is
      an efficient normative measure of grammatical production capacity. For specific
      structures, elicitation and narrative may give a different picture of output.
      Elicitation is more facilitative and may more closely reflect grammatical
      knowledge. Target structures were less likely to be used in the narrative, which
      reflects grammatical performance in a cognitively and linguistically demanding
      task.

PMID- 15151191
TI  - Phonological acquisition in preschoolers learning a second language via
      immersion: a longitudinal study.
AB  - Phonological development in first and second languages (L1 and L2 respectively)
      has not been extensively studied in young children who are acquiring a second
      language via immersion. This lack of information is unfortunate, as the number of
      children who are acquiring a second language in this context is growing and such
      children make up a part of the clinical caseload of many speech-language
      pathologists. To address the need for information regarding phonological
      development of children acquiring a second language in immersion, the present
      investigation sought to provide longitudinal data on the development of both L1
      and L2 phonologies. Five preschoolers who were acquiring English as a L2 and who
      spoke different L1s participated in the study. A picture identification task was
      used to assess productive phonological skills in L1 and English. Analyses
      included a description of the children's phonetic inventories, accuracy rates,
      and non-target response patterns. Both within child (across languages) and
      between child comparisons were made to discern possible patterns of use and to
      identify factors that may impact phonological skill in the L1 and L2. Results of
      the investigation suggest that children who are learning a L2 utilize their
      knowledge of the L1 to aid them in acquiring the phonological system of the L2.
      At the same time, they appear to maintain, at least as measured via perceptual
      analysis of their speech, distinct phonological systems.

PMID- 15151192
TI  - Equal appearing interval and visual analogue scaling of perceptual roughness and
      breathiness.
AB  - One of the factors that affects the reliability of perceptual voice evaluation is
      the rating scale. Equal-appearing interval (EAI) and visual analogue (VA) scales
      are the two most common scales used and have attracted much attention in recent
      studies of perceptual voice evaluation. Available findings are contradictory,
      with one study finding the EAI scale to be more desirable while an earlier study
      showed equivocal results. The objective of the present study was to compare the
      reliability of using an 11-point EAI scale and a VA scale, each of 10cm long, for
      perceptual voice quality evaluation. Thirty listeners with no prior experience in
      perceptual voice evaluation were asked to rate the breathy and rough qualities of
      28 voice samples. The results showed that the listeners demonstrated a
      significantly higher intra-rater agreement and lower inter-rater variability in
      rating the two perceptual voice qualities using the EAI scale, when compared to
      the VA scale. However, listeners tend to show more bias in using certain points
      on the EAI scale than on the VA scale. In addition, a linear relationship was
      found between the EAI and VA ratings, suggesting the psychoperceptual
      characteristics of breathy and rough qualities could be captured equally well by
      the EAI and VA scales. Since the ease of use of the rating scale is an important
      consideration in clinical situations, the 11-point, 10cm long EAI scale is
      therefore more preferable, although not necessarily more superior, than the VA
      scale for evaluating breathy and rough qualities.

PMID- 15151193
TI  - Analyzing health care operations using ABC.
AB  - The evolution of health care created a climate in which cost was subordinate to
      medical treatment. Current reimbursement constraints have increased the need for
      providers to be cost conscious, but they have discovered that current accounting
      practices do not provide the appropriate information to determine the cost of
      service or make decisions. This article argues that activity-based costing (ABC)
      can bridge the gap between the medical and financial communities and provide a
      foundation for performance improvement.

PMID- 15151194
TI  - Pharmaceutical "charge compression" under the Medicare outpatient prospective
      payment system.
AB  - Analysis of the actual acquisition costs of a sample of pharmaceuticals
      demonstrates that payment rates for pharmaceutical therapies under the Medicare
      hospital outpatient prospective payment system (OPPS) are systematically biased
      against fully reimbursing high cost pharmaceutical therapies. Under the Centers
      for Medicare and Medicaid Services' (CMS') methodology, which assumes a constant
      markup, a bias in the cost estimate occurs when hospitals apply below average
      markups in establishing their charges for pharmaceutical products with above
      average costs. We developed a model of the relationship between product costs and
      charge markups. The logarithmic model shows that an increase in the acquisition
      cost per episode can be expected to lead to a reduction in the charge markup
      multiple. When markups for pharmaceuticals decline as acquisition cost increases,
      a rate-setting methodology that assumes a constant markup results in
      reimbursement for higher cost products that can be far below acquisition cost.
      The incentives in the payment system could affect site of care choices and
      beneficiary access.

PMID- 15151196
TI  - Can community hospitals survive without large scale health reform?
AB  - This nation's not-for-profit community hospitals, numbering over 4000 and
      providing the largest percentage of all hospital services to the US population,
      are threatened as never before by erratic reimbursement, reduced capital access
      and, more recently, by physicians who now compete both by virtue of
      outpatient/ambulatory services and by starting "specialty hospitals." This
      article examines some of these trends and their implications, raising the issue
      of whether it is time for major restructuring of our reimbursement systems and
      other significant health reforms.

PMID- 15151195
TI  - Performance of major teaching hospitals during the 1990s: adapting to turbulent
      times.
AB  - A panel design was used to analyze changes in performance variables related to
      profitability, volume, and efficiency in a national sample of major teaching
      hospitals from 1990 to 1999. After steady increases beginning in 1990, the
      average total margin ratio peaked in 1996 and by 1999 it declined by almost 50
      percent. Average operating margins were negative every year. Major teaching
      hospitals responded to financial pressures by expanding outpatient activity,
      reducing length of stay, downsizing inpatient capacity, and increasing labor
      productivity. Membership in multi-hospital systems increased by over 70 percent
      through the 1990s. Increases in average real cost per adjusted admission peaked
      in 1994 and fell by 6 percent from 1994 to 1999.

PMID- 15151197
TI  - Uncharitable and out of control?
AB  - This article explores the current state of the law governing partnerships and
      other collaborations between tax-exempt health care organizations and private
      health care providers. The author sets out the regulatory maze through which
      exempt entities and private parties must navigate in attempting to maintain
      Internal Revenue Code (IRC) Section 501(c)(3) status for the exempt entity in
      these relationships. The article discusses and comments on general principles
      through an examination of case law, statutes, regulations, revenue rulings,
      revenue procedures, and information letters, as well as state law issues, with an
      emphasis on maintaining charitable purposes, effecting control, and dealing with
      ownership and compensation issues.

PMID- 15151198
TI  - Physician office space in an ambulatory surgical center.
AB  - Medicare requires that ambulatory surgical centers (ASCs) be operated exclusively
      for the purpose of providing surgical services to patients who do not require
      hospitalization. As a result, ASCs have been reluctant to establish physician
      office space within their facilities for non-surgical procedures due to fear of
      losing their Medicare certification for failure to satisfy the exclusivity
      requirement. Recently, however, the Centers for Medicare and Medicaid Services
      (CMS) clarified its position on the exclusivity issue, stating that if an ASC
      follows certain criteria, it can establish physician office space within its
      facility without violating the exclusivity requirement or jeopardizing its
      Medicare certification.

PMID- 15151199
TI  - Getting to know the customer: employer strategy for provider organizations.
AB  - Employers are again facing double-digit increases in health insurance premiums,
      while a weaker labor market makes cost-shifting and other cost containment
      activities more feasible for employers. In this market, providers must better
      understand employers' demands and develop a strategy to reach out to employers.

PMID- 15151200
TI  - Health care consumer reports: an evaluation of employer perspectives.
AB  - The proliferation of health care consumer reports (also known as "consumer
      guides," "report cards," and "performance reports") designed to assist consumers
      in making more informed health care decisions makes it vital to understand the
      perspective of employers who provide the vast majority of health insurance to the
      working population regarding the use of these reports. There is little empirical
      evidence on how consumer reports are used by employers to make health care
      purchasing decisions. This study fills that gap by surveying 154 businesses in
      Boone County, Missouri, regarding their evaluation of a consumer guide. The
      majority of employers surveyed indicate that the report will not have a direct
      effect on their health care purchasing decisions. However, they indicate that the
      reports are "positive and worthwhile" and their responses reflect a favorable
      view of the health care organization that developed and disseminated the report.
      Additionally, findings indicate that employers generally prefer consumer reports
      as a means to compare local health care institutions, rather than reviewing
      national averages to locate the same information. Report developers should take
      precautions to determine the intent of such reports, as they may not achieve the
      objective of changing employers' health care purchasing behavior.

PMID- 15151201
TI  - Enhanced accuracy and reliability of HER-2/neu immunohistochemical scoring using
      digital microscopy.
AB  - We evaluated the HER-2/neu status of 129 invasive breast cancer specimens for
      gene amplification by fluorescence in situ hybridization (FISH) and protein
      overexpression by immunohistochemical analysis. Each immunohistochemically
      stained slide was interpreted on a standard microscope independently by 10
      pathologists. Separately, each pathologist reviewed the same slide set with the
      assistance of digital microscopy. A total of 1,258 manual immunohistochemical
      scores and 1,269 digital microscopy immunohistochemical scores were completed.
      When the same 10 pathologists scored the same immunohistochemical slides with the
      assistance of digital microscopy, each reviewer improved concordance with FISH,
      and overall concordance with immunohistochemical analysis improved significantly,
      to 93% (P < .001). The interrater kappa was used to compare interobserver
      agreement in HER-2 immunohistochemical scoring for manual and digital microscopy
      interpretation. Significant improvement in interobserver agreement (kappa = 0.51
      vs 0.86; P < .001) was achieved when HER-2 immunohistochemical analysis was
      scored with the assistance of the digital microscope. The assistance of digital
      microscopy improves the accuracy and reliability of HER-2 immunohistochemical
      analysis. These data suggest that documented discrepancies between HER-2
      immunohistochemical analysis and FISH reflect predominantly errors in manual
      immunohistochemical interpretation as opposed to immunohistochemical reagent
      limitations.

PMID- 15151202
TI  - HER-2 testing in breast cancer using immunohistochemical analysis and
      fluorescence in situ hybridization: a single-institution experience of 2,279
      cases and comparison of dual-color and single-color scoring.
AB  - We analyzed concordance between immunohistochemical analysis and fluorescence in
      situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D
      FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to
      amplified or nonamplified categories. The assays were performed on formalin
      fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas.
      Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+,
      3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH)
      or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were
      interpreted as positive gene amplification. We found 547 (24.0%) cases positive
      immunohistochemically, 326 (14.3%) by D-FISH, and 351 (15.4%) by S-FISH. Overall
      concordance in HER-2 status with immunohistochemical analysis was 87% for D-FISH
      and 86% for S-FISH. Excellent concordance was found among groups scored
      immunohistochemically as 0, 1+, and 3+ (with D-FISH, 97%; with S-FISH, 96%). The
      most discordant category was the group scored 2+ immunohistochemically, in which
      only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results
      were discordant in 89 tumors (4%), of which 8 (9%) had 3+ immunohistochemical
      staining and none showed high-level HER-2 amplification. Among all FISH(+)
      tumors, 10% were negative by immunohistochemical analysis, and notably almost
      half (47%) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9);
      the clinical significance of these findings warrants further investigation.

PMID- 15151204
TI  - Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia,
      bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous
      bronchioloalveolar carcinoma of the lung.
AB  - We examined the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemical
      staining in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma
      (BAC), and adenocarcinoma with mixed subtypes (MX) to study the association
      between the biologic features of adenocarcinoma of the lung and mucin expression.
      MUC1 expression was decreased significantly in the progression from AAH through
      BAC to MX, while the levels of expression of MUC2, MUC5AC, MUC6, and depolarized
      MUC1 were increased significantly. Alterations in the expression of depolarized
      MUC1, MUC5AC, and MUC6 were correlated significantly with p53 gene abnormalities.
      Depolarized MUC1 expression also was correlated significantly with Ki-67
      expression, and down-regulation of MUC1 expression and up-regulation of MUC6
      expression were correlated significantly with tumor size. Our results suggest
      that the expression of these mucins might be associated with the progression of
      adenocarcinoma of the lung.

PMID- 15151203
TI  - RT-PCR for mammaglobin genes, MGB1 and MGB2, identifies breast cancer
      micrometastases in sentinel lymph nodes.
AB  - In the present study, we examined the expression of the mammaglobin genes, MGB1
      and MGB2, in the sentinel lymph nodes (SLNs) of patients with breast cancer and
      compared our results with the histologic status of the same SLNs. Compared with
      immunohistochemical staining for cytokeratin 8, which detected metastases in 17
      of 42 patients, reverse transcription-polymerase chain reaction (RT-PCR) for MGB1
      or MGB2 genes was positive in 22 patients. The concordance between the expression
      of any mammaglobin and histologic status was 79% (33/42), with a sensitivity of
      88% and specificity of 72%. The detection of patients with metastases was more
      sensitive when testing for both MGB1 and MGB2 (P < .0001) rather than MGB2 (P <
      .0005) or MGB1 (P < .05) alone. The increased detection rate relative to
      histologic examination suggests that using RT-PCR for the mammaglobin genes might
      identify patients at higher risk compared with patients with negative RT-PCR
      results.

PMID- 15151205
TI  - Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid
      pseudopapillary tumor of the pancreas: a rare neoplasm of elusive origin but
      characteristic cytomorphologic features.
AB  - Clinical histories, endoscopic ultrasound (EUS)-guided fine-needle aspiration
      (FNA) material, and immunohistochemical stains performed on cell block samples of
      6 solid-pseudopapillary tumors of the pancreas (SPTPs) were reviewed in the cases
      of 5 females (13-58 years) and 1 man (57 years); all had abdominal pain.
      Preliminary cytologic diagnoses at endoscopy included 1 SPTP 2 low-grade
      neoplasms, and 3 pancreatic endocrine tumors. Variable numbers of branching
      fragments with central capillaries and myxoid stroma were seen in the smears of 5
      of 6 cases but were more apparent in the cell block material of all cases. The
      cells had bland nuclear features and rare grooves. Extensive necrosis was noted
      in 1 case and rare mitotic figures in 1. SPTPs showed strong cellular
      immunoreactivity for vimentin and focal weak keratin reactivity. Neuron-specific
      enolase, alpha1-antitrypsin, and alpha1-antichymotrypsin stains performed in 2
      cases were strongly positive. Subsequent surgical resection confirmed all
      diagnoses. EUS-guided FNA diagnosis of SPTP is accurate. The characteristic
      branching papillae with myxoid stroma are best seen in cell block slides.
      Clinical setting, cytomorphologic features, and immunostains of the cell block
      help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma,
      and papillary mucinous carcinoma.

PMID- 15151206
TI  - Barriers to optimal assessment of lymph nodes in colorectal cancer specimens.
AB  - Lymph node (LN) retrieval and assessment is critically important for accurate
      staging and treatment planning in colorectal cancer (CRC). Practicing
      pathologists in Ontario were identified and surveyed by phone to identify
      barriers to optimal retrieval and assessment. Of the pathologists surveyed, 57.9%
      were aware of guidelines for LN retrieval in CRC, but only 25.0% identified that
      a minimum of 12 LNs are necessary for accurate designation of node negativity. An
      important role exists for an education strategy aimed at bridging the knowledge
      gap among practicing pathologists and surgeons regarding optimal LN assessment in
      CRC specimens.

PMID- 15151207
TI  - Microdissection-based genotyping assists discrimination of reactive gliosis from
      glioma.
AB  - We used molecular anatomic pathology to determine the mutational status (loss of
      heterozygosity [LOH]) to make the distinction between reactive gliosis and glial
      neoplasia. LOH has been shown to be absent in reactive states and present in
      neoplastic cellular proliferations. Three groups of patient specimens were
      analyzed: group 1, reactive gliosis (n = 15); group 2, gliomas of varying
      histologic type and grade (n = 54); group 3, diagnostically challenging reactive
      gliosis vs glioma (n = 16). No group 1 cases (0/15 [0%]) showed allelic loss,
      whereas all high-grade glial neoplasms, a subset of group 2 (35/35 [100%])
      manifested at least 1 allelic loss alteration, with most cases (33/35 [94%])
      displaying 2 or more such changes. During a look forward at the group 3 patients,
      clinical history clarified the problematic diagnosis in a subset of 11 patients:
      8 (73%) of 11 clinical outcomes were predicted correctly by our analysis. The
      molecular anatomic pathology approach outlined herein is designed for minute,
      formalin-fixed, paraffin-embedded specimens, which are encountered in everyday
      surgical pathology practice. Molecular anatomic pathology opens the possibilities
      of molecular analysis to everyday pathology practice.

PMID- 15151208
TI  - Histologic grading of noninvasive papillary urothelial tumors: validation of the
      1998 WHO/ISUP system by immunophenotyping and follow-up.
AB  - Cytokeratin (CK) 20, Ki-67, and p53 were applied to 84 noninvasive papillary
      urothelial tumors graded by the 1973 World Health Organization (WHO) and 1998
      WHO/International Society of Urological Pathology (ISUP) systems. In the WHO/ISUP
      classification, all benign lesions showed normal CK20 staining and all carcinomas
      showed abnormal staining. The Ki-67 index was significantly different between
      benign and malignant lesions (P < .05) and between low- and high-grade carcinomas
      (P < .001). p53 was negative in all benign lesions, with a significant difference
      between low- and high-grade carcinomas (P < .001). Tumor recurrence was
      significantly different between low- and high-grade carcinomas (no recurrences
      among the papillary urothelial neoplasms of low malignant potential). By the 1973
      WHO classification, normal CK20 staining was present both in benign lesions and
      in carcinomas. Ki-67 staining did not distinguish between grade 2 and grade 3
      carcinomas (P > .05), and there was no difference in p53 staining in grades 1 and
      2 carcinomas (P > .05). Recurrences were not different between grades 1, 2, and 3
      carcinomas. All biologic markers studied and tumor recurrences were significantly
      different among papillary lesions classified by the WHO/ISUP system but not by
      the 1973 WHO system, validating the predictive value of the WHO/ISUP system and
      providing objective markers for the grading of papillary urothelial tumors.

PMID- 15151210
TI  - Hodgkin disease associated with T-cell non-Hodgkin lymphomas: case reports and
      review of the literature.
AB  - Non-Hodgkin lymphoma (NHL) is more likely to develop in patients with Hodgkin
      disease (HD) than in the general population. Although reports of synchronous or
      metachronous HD and NHL are not uncommon in the literature, the biologic
      relationship of these 2 malignant neoplasms often is unclear. A larger-than
      expected fraction of NHLs occurring in patients with HD are of the T-cell
      phenotype. We report 1 synchronous and 3 metachronous cases of HD and T-cell NHL.
      In 2 cases, the 2 tumors are unlikely to be related clonally. In the other 2
      cases, however, T-cell receptor rearrangement studies demonstrated the presence
      of the same rearranged clone in both tumor specimens, suggesting that they share
      a common precursor or that one arose by transformation of the other. These
      observations imply that, similar to the observations in B-cell NHLs occurring
      with HD, a subset of synchronous and metachronous T-cell NHLs and HD may be
      related clonally.

PMID- 15151209
TI  - Automated flow cytometric analysis of blood cells in cerebrospinal fluid:
      analytic performance.
AB  - We compared the performance of an automated method for obtaining RBC and WBC
      counts and WBC differential counts in cerebrospinal fluid (CSF) samples with the
      reference manual method. Results from 325 samples from 10 worldwide clinical
      sites were used to demonstrate the accuracy, precision, and linearity of the
      method. Accuracy statistics for absolute cell counts showed a high correlation
      between methods, with correlation coefficients for all reportable absolute counts
      greater than 0.9. Linearity results demonstrated that the method provides
      accurate results throughout the reportable ranges, including clinical decision
      points for WBCs of 0 to 10/microL. Interassay precision and intra-assay precision
      for the ADVIA 120 (Bayer HealthCare, Tarrytown, NY) method were acceptable at all
      levels. The ADVIA 120 CSF Assay enumerates and differentiates cells via flow
      cytometry in a minimally diluted sample, improving the analysis of typically
      hypocellular CSF samples. Study results demonstrate that the automated ADVIA 120
      CSF Assay is an acceptable alternative to the labor-intensive manual method.

PMID- 15151211
TI  - Clusterin, a marker for anaplastic large cell lymphoma immunohistochemical
      profile in hematopoietic and nonhematopoietic malignant neoplasms.
AB  - We evaluated the immunohistochemical staining profile of clusterin in paraffin
      sections of 143 neoplasms (non-Hodgkin lymphoma, 83, including 41 anaplastic
      large cell lymphomas [ALCLs]; Hodgkin lymphoma, 17; primary and metastatic
      carcinoma, 30; and other neoplasms, 13). In 40 of 41 ALCLs (34 systemic, 7
      cutaneous), neoplastic cells revealed clusterin reactivity characterized by a
      Golgi staining pattern. The proportion of reactive cells varied with more than
      25% positive cells in the majority of cases. In 7 non-Hodgkin lymphomas of other
      types, fine cytoplasmic (3 cases) or strong membranous reactivity (4 cases) was
      observed for clusterin. In Hodgkin lymphoma, rare Reed-Sternberg cells exhibited
      focal cytoplasmic or membranous clusterin positivity. In the nonhematopoietic
      neoplasms, a Golgi staining pattern was apparent in only 2 cases, 1 lobular
      carcinoma of the breast and 1 poorly differentiated colonic carcinoma; however,
      cytoplasmic reactivity was noted in 12 of 30 carcinomas and 1 of 5 neuroendocrine
      neoplasms. A Golgi pattern of reactivity for clusterin seems highly
      characteristic of ALCL among hematopoietic neoplasms, but also might be observed
      in rare nonhematopoietic tumors, necessitating the use of a broad
      immunohistochemical panel for evaluation of poorly differentiated neoplasms of
      indeterminate derivation.

PMID- 15151212
TI  - Histologic patterns of lung infiltration of B-cell, T-cell, and Hodgkin
      lymphomas.
AB  - Secondary lung infiltration by lymphomas occurs frequently. To our knowledge,
      however, no recent studies have attempted to discriminate histologic patterns of
      lung infiltration in the lymphoma subtypes. We retrospectively evaluated the
      frequency of lung infiltration and the respective infiltration patterns by
      lymphomas at autopsy, during an 11-year period. Lymphomas were classified
      according to the 2001 World Health Organization Classification of hematologic
      malignancies in B-cell, T-cell, and Hodgkin lymphomas (HLs). In 21,157 autopsies,
      414 reports with lymphoma diagnosis were reviewed histologically, and 85 showed
      lung infiltration (20.5%). We studied 14 HLs, 43 B-cell lymphomas, and 20 T-cell
      lymphomas. Five infiltration patterns were identified: peribronchial
      perivascular, nodular alveolar, interstitial, and pleural. Approximately half of
      the lymphomas had more than 1 infiltration pattern (mean, 1.7); peribronchial
      perivascular and pleural were the most frequent. The frequency of nodular
      infiltration was larger in HL than in B-cell lymphomas. T-cell lymphomas had a
      larger frequency of the interstitial infiltration pattern compared with B-cell
      lymphomas. Recognizing the frequency and patterns of lung infiltration in the
      light of a more recent classification is certainly useful for physicians dealing
      with lymphoma diagnostic procedures, such as radiologists and pathologists.

PMID- 15151213
TI  - HIV-associated Hodgkin lymphoma: a clinicopathologic and immunophenotypic study
      of 45 cases.
AB  - We retrospectively analyzed 45 cases of HIV-associated Hodgkin lymphoma (HIV-HL).
      HIV-HL generally is a disease of young white men (mean age, 40.1 years) who
      acquired HIV infection by homosexual or bisexual behavior (68%), intravenous drug
      use (24%), and/or blood transfusion (8%). The mean interval between the diagnosis
      of HIV and HIV-HL was 5.2 years. Morphologic classification of nodal biopsy
      specimens (2001 World Health Organization criteria) included 15 mixed cellularity
      Hodgkin lymphomas (MCHLs), 14 nodular sclerosis Hodgkin lymphomas (NSHLs), 9
      lymphocyte depleted Hodgkin lymphomas (LDHLs), and 7 classic Hodgkin lymphomas,
      type not further categorized. The Hodgkin-Reed-Sternberg (HRS) cells expressed
      positive immunoreactivity with fascin (30/30 [100%]), CD30 (35/37 [95%]), CD15
      (32/36 [89%]), bcl-X(L) (25/31 [81%]), bcl-2 (15/29 [52%]), CD20 (4/34 [12%]),
      bcl-6 (3/28 [11%]), and Epstein-Barr virus latent membrane protein-1 (32/33
      [97%]) and were nonreactive for CD138/syndecan-1. CD4 and CD8 immunostaining
      showed an inverted CD4/CD8 ratio (<1/20) in all cases. At diagnosis, most
      patients (n = 27) had high-stage disease (IV(E)) associated with an aggressive
      course (16% 5-year survival). LDHL behaved more aggressively than MCHL and NSHL
      (15% vs 40%, 5-year survival, respectively), as did disease with a sarcomatoid
      pattern (11% 5-year survival). Chemotherapy and radiotherapy proved efficacious
      in a minority of these patients.

PMID- 15151215
TI  - Endometrial adenocarcinoma associated with elevated serum concentrations of the
      free beta subunit of human chorionic gonadotropin.
AB  - We report a case of a histologic grade II endometrial adenocarcinoma without
      trophoblastic differentiation in a 24-year-old woman with an elevated serum
      concentration of human chorionic gonadotropin (hCG) and with no evidence of
      pregnancy. Serum and urine specimens were used to study the hCG immunoreactivity.
      Qualitative tests performed on serum and urine using 5 different assays produced
      conflicting results. The hCG concentration in serum and urine was quantified
      using assays designed to detect different molecular forms of the molecule;
      analysis revealed that serum hCG immunoreactivity was due entirely to the
      presence of the free beta subunit. Immunohistochemical analysis performed on
      tissue samples showed strong cytoplasmic staining for hCG. While hCG is a well
      recognized tumor marker in gynecologic malignant neoplasms, immunoreactivity most
      often is due to the presence of both intact molecule and the free beta subunit.
      To our knowledge, this is the first report of an endometrial adenocarcinoma
      producing only the free beta subunit of hCG.

PMID- 15151214
TI  - Comparative evaluation of schistocyte counting by an automated method and by
      microscopic determination.
AB  - Schistocytes are circulating RBC fragments. The morphologic identification of
      schistocytes is difficult because the shapes to which they correspond are still
      under discussion. Automated hematology systems permit the possibility of direct
      measurement of RBC fragments. We compared schistocyte counts performed by
      different biologists and technicians with the automated counts by the ADVIA 120
      (Bayer Health Care, Tarrytown, NY). The agreement between the ADVIA 120 and the
      average of the observers gives a correlation coefficient of 0.7274 (95%
      confidence interval, 0.6285-0.8019). The ADVIA 120 has a tendency to overestimate
      the count (average, +0.445%). No false-negative case was recorded. The maximum
      sensitivity (detection of 100% of samples with schistocytes) of the analyzer was
      determined at a threshold value of 0.25%, but the specificity was low (20%).
      Therefore, a blood smear examination remains necessary to confirm schistocyte
      presence. However, the clinical features correlated particularly with negative
      automated RBC fragments, and the high negative predictive value of RBC fragments
      ruled out thrombotic events (macroangiopathies or microangiopathies).

PMID- 15151216
TI  - The binding of acetaminophen, lidocaine, and valproic acid to human milk.
AB  - The binding of acetaminophen, lidocaine, and valproic acid to pooled normal
      mature human milk was studied in vitro by using equilibrium dialysis. Scatchard
      analysis revealed high-affinity, low-capacity binding for acetaminophen (Ka
      [affinity constant of association], 1.47 x 10(4) L/mol; Bo [concentration of
      binding sites], 9.01 x 10(-4) mol/L) and some minimal, nonspecific binding.
      Binding ranged up to 85%. For lidocaine, low-affinity, high-capacity binding was
      noted (Ka, 1.42 x 10(2) L/mol; Bo, 1.69 x 10(-2) mol/L). Binding ranged up to
      72%. For valproic acid, only minimal, nonspecific binding was noted at low drug
      concentrations with binding ranging up to 64%. The binding of these drugs to milk
      might enhance their excretion and subsequent ingestion by infants who are breast
      fed. In addition, the low pH of the milk (6.24) may cause "ion trapping" of
      acetaminophen (pKa, 9.5) and lidocaine (pKa, 7.9).

PMID- 15151217
TI  - Cytotoxic molecule expression and epithelial cell apoptosis in oral and cutaneous
      lichen planus.
AB  - We evaluated the expression of T cell-restricted intracellular antigen (Tia-1),
      granzyme B, and perforin by lymphocytes and the degree of epithelial apoptosis in
      oral and cutaneous lichen planus (LP) in 51 untreated cases, including 27 oral LP
      (OLP) and 24 cutaneous LP (CLP) cases. The number of total dermal-positive
      lymphocytes in OLP and CLP was similar, indicating similar activity of the
      inflammatory process. Intraepithelial Tia-1-positive, perforin-positive, and
      granzyme B-positive lymphoid cells were more numerous in OLP than in CLP (P <
      .05). The epithelial cell apoptotic index (AI) was increased significantly in OLP
      (P < .05), particularly in erosive-atrophic variants. A linear correlation
      between AI and the mean +/- SEM number of intraepithelial and dermal perforin+
      cells (6.85 +/- 2.44 and 27.48 +/- 10.19, respectively), per 10 high-power fields
      for OLP and for CLP (1.17 +/- 0.88 and 10.42 +/- 5.74, respectively), was found
      (intraepithelial, r = 0.50; dermal, r = 0.51; P < .01). These data suggest a
      pivotal role for perforin in triggering epithelial cell apoptosis. The
      differences of infiltrating cytotoxic cells and related AI observed in OLP and
      CLP are in keeping with the clinical behaviors that distinguish these LP
      variants.

PMID- 15151218
TI  - Postoperative frozen section?

PMID- 15151219
TI  - Rapid, specific detection of Salmonella Enteritidis in pooled eggs by real-time
      PCR.
AB  - An assay was developed for the specific detection of Salmonella Enteritidis in
      eggs with the use of an application of the fluorogenic 5' nuclease assay
      (TaqMan). In this assay, a segment of the gene sefA specific to Salmonella group
      D strains such as Salmonella Enteritidis was used. The amplification of the
      target gene products was monitored in real-time by incorporating a fluorescent
      dye-labeled gene-specific probe in the PCR reaction. This method correctly
      detected and distinguished Salmonella Enteritidis from nearly 50 of non-group D
      Salmonella and other non-Salmonella strains. Detection of the sefA gene was
      linear for DNA extracted from approximately 10(2) to 10(9) CFU/ml in phosphate
      buffered saline and 10(3) to 10(8) CFU/ml in raw egg. In two trials, when applied
      to detection of Salmonella Enteritidis in homogenized egg pools and compared with
      conventional culture methods, the newly developed PCR method yielded a 100%
      correlation with results obtained by a conventional culture method. However, the
      PCR method required only 2 days, compared to the 5 days required by the culture
      method. The sensitivity of this assay was approximately less than 1 CFU/600 g of
      egg pool. The real-time PCR assay proved to be a rapid, highly sensitive test for
      detection and quantification of low concentrations of Salmonella Enteritidis in
      egg samples.

PMID- 15151220
TI  - Relative effectiveness of the Bacteriological Analytical Manual method for the
      recovery of Salmonella from whole cantaloupes and cantaloupe rinses with selected
      preenrichment media and rapid methods.
AB  - Soak and rinse methods were compared for the recovery of Salmonella from whole
      cantaloupes. Cantaloupes were surface inoculated with Salmonella cell suspensions
      and stored for 4 days at 2 to 6 degrees C. Cantaloupes were placed in sterile
      plastic bags with a nonselective preenrichment broth at a 1:1.5 cantaloupe weight
      to-broth volume ratio. The cantaloupe broths were shaken for 5 min at 100 rpm
      after which 25-ml aliquots (rinse) were removed from the bags. The 25-ml rinses
      were preenriched in 225-ml portions of the same uninoculated broth type at 35
      degrees C for 24 h (rinse method). The remaining cantaloupe broths were incubated
      at 35 degrees C for 24 h (soak method). The preenrichment broths used were
      buffered peptone water (BPW), modified BPW, lactose (LAC) broth, and Universal
      Preenrichment (UP) broth. The Bacteriological Analytical Manual Salmonella
      culture method was compared with the following rapid methods: the TECRA Unique
      Salmonella method, the VIDAS ICS/SLM method, and the VIDAS SLM method. The soak
      method detected significantly more Salmonella-positive cantaloupes (P < 0.05)
      than did the rinse method: 367 Salmonella-positive cantaloupes of 540 test
      cantaloupes by the soak method and 24 Salmonella-positive cantaloupes of 540 test
      cantaloupes by the rinse method. Overall, BPW, LAC, and UP broths were equivalent
      for the recovery of Salmonella from cantaloupes. Both the VIDAS ICS/SLM and TECRA
      Unique Salmonella methods detected significantly fewer Salmonella-positive
      cantaloupes than did the culture method: the VIDAS ICS/SLM method detected 23 of
      50 Salmonella-positive cantaloupes (60 tested) and the TECRA Unique Salmonella
      method detected 16 of 29 Salmonella-positive cantaloupes (60 tested). The VIDAS
      SLM and culture methods were equivalent: both methods detected 37 of 37
      Salmonella-positive cantaloupes (60 tested).

PMID- 15151221
TI  - The biogenic amine tyramine modulates the adherence of Escherichia coli O157:H7
      to intestinal mucosa.
AB  - The environmental factors that influence the ability of Escherichia coli O157:H7
      to attach to the intestinal mucosa are incompletely understood. In the present
      study, the ability of one of the most common biogenic amines present in food,
      tyramine, to influence the ability of E. coli O157:H7 to adhere to murine cecal
      mucosa was examined. Ex vivo full-thickness sheets of murine cecum were mounted
      in Ussing chambers, which preserved the enteric nervous system innervation of the
      luminal epithelia and thereby allowed us to achieve a closer approximation of
      bacterial adherence than would be encountered in vivo. After exposure of the
      luminal aspect of the cecum to tyramine, E. coli O157:H7 was added for 90 min.
      The cecal tissue was then removed and washed, and adhered E. coli O157:H7 was
      enumerated using a selective medium. Tyramine significantly increased E. coli
      O157:H7 adherence to cecal mucosa when compared to that of controls. The 50%
      effective concentration of tyramine was 92.6 microM. Specific adrenergic
      antagonists were then employed to examine whether the effect of tyramine was
      mediated through alpha- or beta-adrenergic receptors on the intestinal tissue.
      Pretreatment of tissues with either the alpha-adrenergic receptor antagonist
      phentolamine or the beta-adrenergic receptor antagonist propranolol prevented the
      action of tyramine. Measurement of active transepithelial ion transport and ionic
      permeability in the cecal sheets before and after the addition of tyramine and E.
      coli O157:H7 did not show any impairment of tissue viability or transepithelial
      conductance. Further, tyramine did not influence either the growth of E. coli
      O157:H7 or the expression of the intimin attachment factor. The present findings
      suggest that biogenic amines, such as tyramine, present within the food matrix
      influence host susceptibility to E. coli O157:H7 infection.

PMID- 15151222
TI  - In vitro inactivation of Escherichia coli O157:H7 in bovine rumen fluid by
      caprylic acid.
AB  - The antibacterial effect of caprylic acid (35 and 50 mM) on Escherichia coli
      O157:H7 and total anaerobic bacteria at 39 degrees C in rumen fluid (pH 5.6 and
      6.8) from 12 beef cattle was investigated. The treatments containing caprylic
      acid at both pHs significantly reduced (P < 0.05) the population of E. coli
      O157:H7 compared with that in the control samples. At pH 5.6, both levels of
      caprylic acid killed E. coli O157:H7 rapidly, reducing the pathogen population to
      undetectable levels at 1 min of incubation (a more than 6.0-log CFU/ml
      reduction). In buffered rumen fluid at pH 6.8, 50 mM caprylic acid reduced the E.
      coli O157:H7 population to undetectable levels at 1 min of incubation, whereas 35
      mM caprylic acid reduced the pathogen by approximately 3.0 and 5.0 log CFU/ml at
      8 and 24 h of incubation, respectively. At both pHs, caprylic acid had a
      significantly lesser (P < 0.05) and minimal inhibitory effect on the population
      of total anaerobic bacteria in rumen compared with that on E. coli O157:H7. At 24
      h of incubation, caprylic acid (35 and 50 mM) reduced the population of total
      anaerobic bacteria by approximately 2.0 log CFU/ml at pH 5.6, whereas at pH 6.8,
      caprylic acid (35 mM) did not have any significant (P > 0.05) inhibitory effect
      on total bacterial load. Results of this study revealed that caprylic acid was
      effective in inactivating E. coli O157:H7 in bovine rumen fluid, thereby
      justifying its potential as a preslaughter dietary supplement for reducing
      pathogen carriage in cattle.

PMID- 15151223
TI  - Dietary supplementation with Lactobacillus- and Propionibacterium-based direct
      fed microbials and prevalence of Escherichia coli O157 in beef feedlot cattle and
      on hides at harvest.
AB  - The objective of this study was to describe the prevalence of Escherichia coli
      O157 in the feces and on the hides of finishing beef cattle fed a standard diet
      and those fed diets supplemented with direct-fed microbials. Two hundred forty
      steers received one of four treatments throughout the feeding period: (i)
      control: no added microbials; (ii) HNP51: high dose of Lactohacillius acidophilus
      strain NP 51 (10(9) CFU per steer daily) and Propionibacterium freudenreichii
      (10(9) CFU per steer daily); (iii) HNP51+45: high dose of NP 51 (10(9) CFU per
      steer daily), P. freudenreichii (10(9) CFU per steer daily), and L. acidophilus
      NP 45 (10(6) CFU per steer daily); or (iv) LNP51+45: low dose of NP 51 (10(6) CFU
      per steer daily), P. freudenreichii (10(9) CFU per steer daily), and NP 45 (10(6)
      CFU per steer daily). Samples were collected from each animal and analyzed for
      the presence of E. coli O157 using immunomagnetic separation methods on day 0
      (feces), 7 days before harvest (feces), and at harvest (feces and hide). At the
      end of the feeding period, cattle receiving HNP51 were 57% less likely to shed
      detectable E. coli O157 in their feces than were the controls (P < 0.01). For
      animals receiving HNP51+45 and LNP51+45, fecal prevalence did not differ from
      that of the controls. The prevalence of positive hide samples was least among
      cattle receiving HNP51+45 (3.3%); these animals were 79% less likely (P < 0.06)
      to have a positive hide sample than were the controls (prevalence = 13.8%). There
      was poor agreement of the culture results between fecal and hide samples
      collected from the same animal (kappa = 0.08; confidence interval = -0.05 to
      0.2). Cattle supplemented with a high dose of NP 51 had reduced E. coli O157
      prevalence in both fecal and hide samples, indicating that this treatment may be
      an efficacious preharvest intervention strategy.

PMID- 15151224
TI  - Preharvest evaluation of coliforms, Escherichia coli, Salmonella, and Escherichia
      coli O157:H7 in organic and conventional produce grown by Minnesota farmers.
AB  - Microbiological analyses of fresh fruits and vegetables produced by organic and
      conventional farmers in Minnesota were conducted to determine the coliform count
      and the prevalence of Escherichia coli, Salmonella, and E. coli O157:H7. A total
      of 476 and 129 produce samples were collected from 32 organic and 8 conventional
      farms, respectively. The samples included tomatoes, leafy greens, lettuce, green
      peppers, cabbage, cucumbers, broccoli, strawberries, apples, and seven other
      types of produce. The numbers of fruits and vegetables was influenced by their
      availability at participating farms and varied from 11 strawberry samples to 108
      tomato samples. Among the organic farms, eight were certified by accredited
      agencies and the rest reported the use of organic practices. All organic farms
      used aged or composted animal manure as fertilizer. The average coliform counts
      in both organic and conventional produce were 2.9 log most probable number per g.
      The percentages of E. coli-positive samples in conventional and organic produce
      were 1.6 and 9.7%, respectively. However, the E. coli prevalence in certified
      organic produce was 4.3%, a level not statistically different from that in
      conventional samples. Organic lettuce had the largest prevalence of E. coli
      (22.4%) compared with other produce types. Organic samples from farms that used
      manure or compost aged less than 12 months had a prevalence of E. coli 19 times
      greater than that of farms that used older materials. Serotype O157:H7 was not
      detected in any produce samples, but Salmonella was isolated from one organic
      lettuce and one organic green pepper. These results provide the first
      microbiological assessment of organic fruits and vegetables at the farm level.

PMID- 15151225
TI  - Serological methods and selective agars to enumerate Campylobacter from broiler
      carcasses: data from inter- and intralaboratory analyses.
AB  - Routine analytical means to estimate Campylobacter numbers per milliliter of
      carcass rinses are needed in high-sample-throughput poultry laboratories. We
      compared three serological confirmatory tests that were amenable to such a
      setting when used in conjunction with Campy-Line and Campy-Cefex Campylobacter
      selective agars. Pre- and post-chlorinated chiller carcass rinse samples were
      obtained and held on ice, then analyzed 24 h later in two separate laboratories.
      Presumptive counts on both pre- and postchiller samples from between laboratories
      on individual agars and between both agars were highly correlated. Agreement
      among the three serological tests was nearly complete. The use of a premeasured
      and dried latex anti-Campylobacter antibody agglutination test format was
      superior to that of either a liquid latex agglutination format or a direct
      phosphate-buffer microscopic technique in terms of practicality as was the
      inclusion of an unarmed latex control to detect auto agglutination. A routine
      procedure for Campylobacter level estimation was suggested. This procedure, when
      used in conjunction with a serological confirmatory step, should provide
      processors with a means to assess reductions in numbers per milliliter of carcass
      rinses versus strictly presence-absence testing.

PMID- 15151226
TI  - Polyphenol oxidase activity as a potential intrinsic index of adequate thermal
      pasteurization of apple cider.
AB  - In response to increasing concerns about microbial safety of apple cider, the
      U.S. Food and Drug Administration has mandated treatment of cider sufficient for
      a 5-log reduction of the target pathogen. Pasteurization has been suggested as
      the treatment most likely to achieve a 5-log reduction, with Escherichia coli
      O157:H7 as the target pathogen. Regulators and processors need a reliable method
      for verifying pasteurization, and apple cider polyphenol oxidase (PPO) activity
      was studied as a potential intrinsic index for thermal pasteurization. The effect
      of pasteurization conditions and apple cider properties on PPO activity and
      survival of three pathogens (E. coli O157:H7, Salmonella, and Listeria
      monocytogenes) was studied using a Box-Behnken response surface design. Factors
      considered in the design were pasteurization conditions, i.e., hold temperature
      (60, 68, and 76 degrees C), preheat time (10, 20, 30 s), and hold time (0, 15, 30
      s), pH, and sugar content ((o)Brix) of apple cider. Response surface contour
      plots were constructed to illustrate the effect of these factors on PPO activity
      and pathogen survival. Reduction in PPO activity of at least 50% was equivalent
      to a 5-log reduction in E. coli O157:H7 or L. monocytogenes for cider at pH 3.7
      and 12.5 (o)Brix. Further studies, however, are needed to verify the relationship
      between PPO activity and pathogen reduction in cider with various pH and (o)Brix
      values.

PMID- 15151227
TI  - Effectiveness of acidic calcium sulfate with propionic and lactic acid and
      lactates as postprocessing dipping solutions to control Listeria monocytogenes on
      frankfurters with or without potassium lactate and stored vacuum packaged at 4.5
      degrees C.
AB  - The safety of ready-to-eat meat products such as frankfurters can be enhanced by
      treating with approved antimicrobial substances to control the growth of Listeria
      monocytogenes. We evaluated the effectiveness of acidic calcium sulfate with
      propionic and lactic acid, potassium lactate, or lactic acid postprocessing
      dipping solutions to control L. monocytogenes inoculated (ca. 10(8) CFU/ml) onto
      the surface of frankfurters with or without potassium lactate and stored in
      vacuum packages at 4.5 degrees C for up to 12 weeks. Two frankfurter formulations
      were manufactured without (control) or with potassium lactate (KL, 3.3% of a 60%
      [wt/wt] commercially available syrup). After cooking, chilling, and peeling, each
      batch was divided into inoculated (four strains of L. monocytogenes mixture) and
      noninoculated groups. Each group was treated with four different dips: (i)
      control (saline solution), (ii) acidic calcium sulfate with propionic and lactic
      acid (ACS, 1:2 water), (iii) KL, or (iv) lactic acid (LA, 3.4% of a 88% [wt/wt]
      commercially available syrup) for 30 s. Noninoculated frankfurters were
      periodically analyzed for pH, water activity, residual nitrite, and aerobic plate
      counts (APCs), and L. monocytogenes counts (modified Oxford medium) were
      determined on inoculated samples. Surface APC counts remained at or near the
      lower limit of detection (<2 log CFU per frank) on franks with or without KL and
      treated with ACS or LA throughout 12 weeks at 4.5 degrees C. L. monoctogenes
      counts remained at the minimum level of detection on all franks treated with the
      ACS dip, which indicated a residual bactericidal effect when L. monocytogenes
      populations were monitored over 12 weeks. L. monocytogenes numbers were also
      reduced, but not to the same degree in franks made without or with KL and treated
      with LA. These results revealed the effectiveness of ACS (bactericidal effect) or
      LA (bacteriostatic effect) as postprocessing dipping solutions to inhibit or
      control the growth of L. monocytogenes on vacuum-packaged frankfurters stored at
      4.5 degrees C for up to 12 weeks.

PMID- 15151228
TI  - Encapsulation of nisin and lysozyme in liposomes enhances efficacy against
      Listeria monocytogenes.
AB  - The efficacy and stability against Listeria monocytogenes of nisin and lysozyme
      encapsulated in phospholipid liposomes was evaluated. Antimicrobial-containing
      liposomes were prepared by hydrating dried lipids with buffer containing nisin,
      nisin plus the fluorescence probe calcein, or calcein and lysozyme. Mixtures were
      then centrifuged and sonicated, and encapsulated liposomes were collected using
      size-exclusion chromatography. Antimicrobial concentration in liposomes was
      determined by bicinchoninic acid assay prior to determination of antimicrobial
      activity against strains of L. monocytogenes. When nisin was encapsulated in
      liposomes, protein concentrations of 0.39, 0.27, and 0.23 mg/ml for
      phosphatidylcholine (PC), PC-cholesterol (7:3), and PC-phosphatidylglycerol (PG)
      cholesterol (5:2:3), respectively, were obtained. Encapsulation of nisin with
      calcein yielded protein concentrations of 0.35, 0.39, and 0.28 mg/ml for PC, PC
      cholesterol, and PC-PG-cholesterol, respectively. Encapsulation of calcein with
      lysozyme resulted in protein concentrations of 0.43, 0.26, and 0.19 mg/ml for PC,
      PC-cholesterol, and PC-PG-cholesterol, respectively. Encapsulated nisin in 100%
      PC and PC-cholesterol liposomes inhibited bacterial growth by >2 log CFU/ml
      compared with free nisin. Growth inhibition with liposomal lysozyme was strain
      dependent, with greater inhibition observed for strains 310 and Scott A with PC
      cholesterol and PC-PG-cholesterol liposomes. Inhibition of L. monocytogenes
      indicated the potential of liposomes to serve as delivery vehicles for
      antimicrobials in foods while improving stability of antimicrobials.

PMID- 15151229
TI  - Inhibition of a methicillin-resistant Staphylococcus aureus strain in Afuega'l
      Pitu cheese by the nisin Z-producing strain Lactococcus lactis subsp. lactis IPLA
      729.
AB  - Methicillin-resistant Staphylococcus aureus strains are a potential threat for
      food safety because foodborne illness caused by methicillin-resistant
      Staphylococcus aureus has been reported even though these strains were only
      associated with nosocomial infections until recently. This article focuses on the
      inhibitory effect of the nisin Z-producing strain Lactococcus lactis subsp.
      lactis IPLA 729 on the growth of Staphylococcus aureus CECT 4013, a methicillin
      resistant strain. S. aureus was inhibited by the presence of the nisin producer
      IPLA 729 in buffered Trypticase soy broth, milk, and Afuega'l Pitu cheese, an
      acid-coagulated cheese manufactured in Asturias, Northern Spain. A reduction of
      3.66 log units was observed in Trypticase soy broth at the end of the incubation
      period. In milk, viable counts of S. aureus were undetectable or were reduced by
      2.16 log units in 24 h depending on the initial inoculum (1.8 x 10(4) and 7.2 x
      10(6) CFU/ml). The staphylococcal strain was also undetected in test cheeses in
      which the nisin Z producer was present whereas 2 log units were detected in
      control cheeses at the end of ripening.

PMID- 15151230
TI  - Variation of the spore population of a natural source strain of Bacillus cereus
      in the presence of inosine.
AB  - The heat resistance of a wild strain of Bacillus cereus spores isolated from
      liquid egg was characterized, and the effect of the nutritional germinant inosine
      on the spore population was then studied, considering different factors such as
      germination temperature, inosine concentration, and age of spore culture. The
      heat resistance clearly indicates that these spores can survive mild heat
      treatments such as those used for cooked refrigerated food of extended durability
      or liquid egg, posing safety problems for these foods with temperature abuse. The
      germination study indicates that temperature, spore age, and the interaction
      between the two were the factors affecting the level of spores remaining after
      the germination process. No significant differences were found for the three
      inosine concentrations used in the study (1, 5, and 10 mM). The highest reduction
      in the spore concentration was reached at 30 degrees C after 120 min, although
      the reduction in the spore counts at germination temperatures of 4 and 8 degrees
      C was also considerable.

PMID- 15151231
TI  - Modeling the prevalence of Bacillus cereus spores during the production of a
      cooked chilled vegetable product.
AB  - In minimally processed vegetable foods, pathogenic spore-forming bacteria pose a
      significant hazard. As part of a quantitative risk assessment, we used Bayesian
      belief methods to model the uncertainty and variability of the number of Bacillus
      cereus spores that can be found in packets of a vegetable puree. The model
      combines specific information from the manufacturer, experimental data on
      inactivation of spores, and expert opinion concerning spore concentrations in the
      raw vegetables and ingredients. Sensitivity analysis revealed that spore
      contamination of added ingredients contributes most uncertainty to the
      assessment. The assessment produced a quantitative estimate of the prevalence of
      B. cereus spores in packets of vegetable puree at the end point of the
      manufacturing process.

PMID- 15151232
TI  - Isolation, identification, and selection of lactic acid bacteria from alfalfa
      sprouts for competitive inhibition of foodborne pathogens.
AB  - Several studies have investigated the control of pathogens on alfalfa sprouts,
      and some treatments have been shown to be effective in reducing pathogen
      populations. However, control methods investigated thus far only provide pathogen
      control at a given point in the sprouting process and can affect germination.
      Competitive inhibition of pathogens with lactic acid bacteria might provide
      pathogen control throughout the sprouting process and up to consumption. The
      purpose of this study was to isolate and identify lactic acid bacteria from
      alfalfa sprouts to inhibit the growth of foodborne pathogens. Fifty-eight lactic
      acid bacteria isolates were obtained from alfalfa seeds and sprouts. These
      isolates were evaluated for inhibitory action against Salmonella enterica,
      Escherichia coli O157:H7, and Listeria monocytogenes by agar spot tests. All
      pathogens were inhibited by 32 (55%) of the isolates, S. enterica by 56 (97%), E.
      coli O157:H7 by 49 (84%), and L. monocytogenes by 41 (71%). The isolates were
      identified by the Analytical Profile Index evaluation of carbohydrate
      utilization. Isolates obtained from a sample of alfalfa seeds and identified as
      Lactococcus lactis subsp. lactis showed zones of inhibition of 4.0 mm or greater
      for all pathogens. One of these isolates, Lactococcus lactis subsp. lactis (L7),
      and an isolate previously obtained, Pediococcus acidilactici (D3), were evaluated
      for competitive inhibition of S. enterica, E. coli O157:H7, and L. monocytogenes
      in deMan Rogosa Sharpe agar and broth. Pathogen populations were significantly
      reduced by day 5. The selected isolates will be further evaluated in future
      studies for inhibitory action toward S. enterica, E. coli O157:H7, and L.
      monocytogenes during sprouting.

PMID- 15151234
TI  - Relation of biogenic amines with microbial and sensory changes of whole and
      filleted freshwater rainbow trout (Onchorynchus mykiss) stored on ice.
AB  - The biogenic amine (BA) content of whole and filleted rainbow trout was monitored
      during ice storage for a period of 18 days and related to respective microbial
      and sensorial changes occurring during the same period. Eight amines, namely,
      putrescine, cadaverine, tyramine, spermidine, tryptamine, beta-phenylethylamine,
      spermine, and histamine, were determined. Agmatine was not detected in any of the
      fish samples. In all cases, concentration of BAs was higher (P < 0.05) in
      filleted compared with whole trout samples. Pseudomonads, H2S-producing bacteria,
      and, to a lesser extent, Enterobacteriaceae were the dominant microorganisms in
      both whole and filleted trout. Higher populations (P < 0.05) of these
      microorganisms were present in filleted trout compared with whole fish samples.
      Of the BAs determined, concentration of putrescine, cadaverine, spermidine,
      tryptamine, and beta-phenylethylamine increased steeply in both whole and
      filleted trout between days 15 and 18 of storage when pseudomonads and H2S
      producing bacteria reached approximately 10(6) to 10(7) CFU/g. For the rest of
      the BAs, including tyramine, histamine, and spermine, a stepwise increase was
      recorded throughout the entire storage period. Interestingly, Enterobacteriaceae
      counts remained below 10(6) throughout the entire storage period, accounting for
      the lower production of histamine. A putrescine value of 13 to 14 mg/kg and a
      spermidine value of approximately 7 mg/kg for both the whole and filleted trout
      obtained after 12 and 9 days, respectively, may be proposed as the upper limit
      for spoilage initiation (freshness indicator) of fresh rainbow trout based on
      sensorial and microbiological (total viable count of 10(6) to 10(7)) data. With
      respect to other amines determined, both tyramine and spermine may also be
      proposed as freshness indicators preferably for whole trout, whereas tryptamine,
      beta-phenylethylamine, histamine, and cadaverine produced only during later
      stages of storage are not suitable as freshness indicators of either whole or
      filleted trout.

PMID- 15151233
TI  - Molecular weight of chitosan influences antimicrobial activity in oil-in-water
      emulsions.
AB  - The objective of this study was to evaluate the antimicrobial efficiency of
      chitosans in oil-in-water emulsions. Model emulsions were prepared with 20% corn
      oil, 1.5% Tween 20, 1.5% Trypticase soy broth, 0.58% acetic acid, and chitosan
      polysaccharide or chitosan oligosaccharide in concentrations of 0, 0.1, 0.2, 0.5,
      and 0.7%. A control containing HCl was included to determine the role of acetic
      acid in the overall antibacterial activity. The pH of samples and controls was
      adjusted to 4.5. Emulsions were inoculated with Listeria monocytogenes (strains
      Scott A and 310) or Salmonella Typhimurium DT104 (strains 2486 and 2576) at a
      level of 10(7) CFU/ml. Inoculated emulsions were incubated at 10 and 25 degrees C
      for 4 days and analyzed for bacterial count every 24 h. Both tested Salmonella
      strains were more susceptible to acetic acid than Listeria. However, L.
      monocytogenes was more affected by chitosan than either Salmonella strain. During
      the storage at 25 degrees C, initial inoculum in the emulsions with 0.58% acetic
      acid and 0.1% chitosan polysaccharide was reduced to below the detection limits
      after 24, 48, 72, or 96 h for L. monocytogenes 310, Salmonella Typhimurium DT104
      2576, Salmonella Typhimurium DT104 2486, or L. monocytogenes Scott A,
      respectively. Chitosan oligosaccharide was less effective against all tested
      bacteria and showed a concentration-dependent effect. The antimicrobial efficacy
      of chitosan was reduced at 10 degrees C, and reduction of microbial loads was
      delayed for approximately 24 h compared with 25 degrees C. Results suggest that
      addition of 0.1% chitosan polysaccharide would be sufficient to ensure the
      microbial safety of oil-in-water emulsions regardless of storage temperature.

PMID- 15151235
TI  - Microbiological quality of rabbit meat.
AB  - World rabbit meat production is estimated to be over 1 million tons, and Spain is
      the third largest producer. Although rabbit meat is marketed and consumed
      worldwide, information on microbiological quality is very scarce. Here, we report
      indicator organisms, spoilage flora, sensory quality, and some physicochemical
      traits of 24 h postmortem chilled rabbit carcasses and prepackaged rabbit meat
      stored chilled in air for 0 to 3 days at the retail level. The mean total
      bacterial count (4.01 +/- 0.48 log CFU/g) for carcasses dressed at a small
      abattoir by a manual process was significantly lower (P < 0.05) than that (4.96
      +/- 0.90 log CFU/g) for carcasses dressed at a large abattoir in automated
      slaughter lines. Both groups of carcasses had mean pH values of 5.98. The
      dominant contaminants on carcasses from the small abattoir were Pseudomonas,
      lactic acid bacteria, and yeasts. These microorganisms and Brochothrix
      thermosphacta were dominant on carcasses from the large abattoir. On prepacked
      hind legs (pH 6.26 +/- 0.18) stored at -1 to +1 degree C (supermarket 1), mean
      aerobic mesophilic count was 5.87 +/- 1.03 log CFU/g, and the major microbial
      groups were Pseudomonas, yeasts, lactic acid bacteria, and B. thermosphacta. On
      prepacked whole carcasses (pH 6.37 +/- 0.18) displayed at -1 to +5 degrees C
      (supermarket 2), mean aerobic mesophilic count was 6.60 +/- 1.18 and the same
      microbial groups were dominant. Relative Escherichia coli incidence was
      supermarket 2 > large abattoir > supermarket 1 > small abattoir. Overall, low
      numbers of coliforms, Enterobacteriaceae, psychrotrophic clostridia, coagulase
      positive staphylococci, and molds were found. Sensory scores, pH values, and L
      lactic acid content differentiated fresh carcasses from retail samples. Data
      obtained suggest that the microflora of chilled rabbit meat are different from
      those found on the meat of other animals.

PMID- 15151236
TI  - Practical application of DNA fingerprinting to trace beef.
AB  - DNA fingerprinting allows the verification of conventional methods used to
      implement beef traceability. At any point along the supply chain, the identity of
      an animal or piece of meat can be checked by comparison of its DNA profile with
      an initial sample. Practical application of DNA fingerprinting to trace beef
      requires a choice of DNA markers as well as the optimization of sampling methods.
      This has been achieved as the result of collaboration between meat technicians
      and geneticists over a period of 4 years. The discrimination power of nine highly
      polymorphic microsatellite markers was evaluated. We propose that three markers
      (with a 0.001 probability that two individual profiles match by chance) are
      adequate for routine tests. Two key points along the production-commercialization
      chain where sampling must be systematic were defined: (i) the tagging of the calf
      (identity control) and (ii) after slaughter (slaughter control), before the
      animal loses its external appearance. The identity control was blood collected on
      a filter paper adapted to the ear tag; the slaughter control was the tagged ear
      itself. These constituted the control samples, which were archived with a code
      matching the individual tag number. Test samples were obtained on a random basis
      from live animals, carcasses, and pieces of meat at cutting halls and at the
      retail outlet and in cases when the verification of identity was needed. The DNA
      profiles of the test samples and the controls were then obtained and compared, to
      verify either an individual identity or the origin of a piece of meat from the
      stated animal.

PMID- 15151238
TI  - Characterization of O157:H7 and other Escherichia coli isolates recovered from
      cattle hides, feces, and carcasses.
AB  - In a previous study, the seasonal prevalence was reported for stx+ Escherichia
      coli O157:H7 in feces and on hides and carcasses of cattle at processing.
      Overall, 1,697 O157:H7 isolates have now been characterized for the incidence of
      (i) eae(O157), hlyA, stx1, and stx2 in the recovered isolates and (ii)
      presumptive rough and presumptive nonmotile isolates. Seven O157:H7 isolates
      (0.4%) lacked stx genes, although they carried eae and hlyA. All but one of the
      isolates carried both eae and hlyA. Approximately two-thirds of the isolates (64%
      when one isolate per sample was considered) carried both stx1 and stx2. E. coli
      O157:H7 cells that harbored both stx1 and stx2 were more often recovered from
      hides in the fall (79% of the fall hide isolates) and winter (84% of the winter
      hide isolates) than in the spring (53%) and summer (59%). Isolates recovered from
      preevisceration carcasses showed a similar but not statistically significant
      trend. Twenty-three of the 25 O157:H7 isolates carrying stx1 but not stx2 were
      recovered during summer. Fifteen presumptive rough and 117 presumptive nonmotile
      stx+ O157:H7 isolates were recovered. Ten (67%) of the presumptive rough isolates
      were recovered during summer. Ninety-five of the presumptive nonmotile isolates
      (81%) were recovered during fall. Forty-eight percent of the false-positive
      isolates (175 of 363) tentatively identified as O157:H7 were O157+ H7- and lacked
      eae(O157), hlyA, and stx. These data suggest that in beef processing samples (i)
      there are minor seasonal variations in the prevalence of stx genes among E. coli
      O157:H7 isolates, (ii) presumptive rough and presumptive nonmotile stx+ O157:H7
      isolates are present, (iii) E. coli O157:H7 isolates lacking stx genes may be
      rare, and (iv) O157+ H7- isolates lacking stx genes can result in many false
      positive results.

PMID- 15151237
TI  - Public health consequences of macrolide use in food animals: a deterministic risk
      assessment.
AB  - The potential impact on human health from antibiotic-resistant bacteria selected
      by use of antibiotics in food animals has resulted in many reports and
      recommended actions. The U.S. Food and Drug Administration Center for Veterinary
      Medicine has issued Guidance Document 152, which advises veterinary drug sponsors
      of one potential process for conducting a qualitative risk assessment of drug use
      in food animals. Using this guideline, we developed a deterministic model to
      assess the risk from two macrolide antibiotics, tylosin and tilmicosin. The scope
      of modeling included all label claim uses of both macrolides in poultry, swine,
      and beef cattle. The Guidance Document was followed to define the hazard, which
      is illness (i) caused by foodborne bacteria with a resistance determinant, (ii)
      attributed to a specified animal-derived meat commodity, and (iii) treated with a
      human use drug of the same class. Risk was defined as the probability of this
      hazard combined with the consequence of treatment failure due to resistant
      Campylobacter spp. or Enterococcus faecium. A binomial event model was applied to
      estimate the annual risk for the U.S. general population. Parameters were derived
      from industry drug use surveys, scientific literature, medical guidelines, and
      government documents. This unique farm-to-patient risk assessment demonstrated
      that use of tylosin and tilmicosin in food animals presents a very low risk of
      human treatment failure, with an approximate annual probability of less than 1 in
      10 million Campylobacter-derived and approximately 1 in 3 billion E. faecium
      derived risk.

PMID- 15151239
TI  - Method of applying sanitizers and sample preparation affects recovery of native
      microflora and Salmonella on whole cantaloupe surfaces.
AB  - Standardized methods for applying sanitizer treatments to cantaloupes and for
      recovering surviving native microflora or Salmonella on inoculated cantaloupe
      after sanitizing are lacking. Accordingly, the objectives of this study were to
      compare four methods for applying sanitizers (dipping, dipping with rotation,
      dipping with agitation, and dipping with rubbing) using 200 ppm of chlorine or 5%
      H2O2, two recovery methods (homogenization of rind plugs in a stomacher or
      blender), and five selective recovery media for Salmonella. Whole cantaloupes
      were submerged in a cocktail of five strains of Salmonella (each at approximately
      2 x 10(8) CFU/ml) for 10 min and allowed to dry for 1 h inside a biosafety
      cabinet and stored at 20 degrees C for approximately 23 h before sanitizing. The
      recovery of Salmonella from whole cantaloupe without sanitizing averaged 5.09 log
      CFU/cm2 by blending and 4.30 log CFU/cm2 by homogenization in a stomacher for the
      five selective agar media. Microbial populations (Salmonella or the indigenous
      aerobic mesophilic bacteria, gram-negative bacteria, lactic acid bacteria,
      Pseudomonas spp., and yeast and mold) were not significantly (P > 0.05) reduced
      by treating with water regardless of the treatment method used. Sanitizing with
      chlorine or H2O2 by dipping, with or without rotation for 2 min, also did not
      reduce microbial populations. However, populations of all classes of native
      microflora and Salmonella were significantly (P < 0.05) reduced by sanitizer
      treatments (2 min) applied with agitation or by rubbing. In general, sanitizer
      treatments applied by rubbing resulted in greater log reductions (by up to 1.7
      log unit) than for treatments applied with agitation. Populations of native
      microflora and Salmonella recovered from cantaloupe were higher (by up to 1.8 log
      unit) by blending compared to homogenization in a stomacher. In most instances,
      selective media used did not differ significantly (P > 0.05) for recovery of
      Salmonella after washing treatments.

PMID- 15151241
TI  - Sensitization of gram-negative and gram-positive bacteria to jenseniin G by
      sublethal injury.
AB  - Jenseniin G, a bacteriocin produced by Propionibacterium thoenii P126, is active
      against related propionibacteria and some lactic acid bacteria and is sporostatic
      to botulinal spores. The objective of this study was to evaluate the effects of
      sublethal stress on jenseniin G activity. Bacillus cereus, Enterococcus faecalis,
      Escherichia coli, Listeria monocytogenes, Salmonella Typhimurium, Shigella
      flexneri, Staphylococcus aureus, and Yersinia enterocolitica were subjected to
      temperature, acid, and osmotic stresses in the presence of jenseniin G. The
      bacteriocin reduced the viability of sublethally injured cultures, although the
      extent of reduction varied with strain and treatment. E. faecalis was the most
      sensitive to temperature stress; no reduction of viable counts occurred in the
      absence of jenseniin G, and a 1.5-log reduction occurred in the presence of
      jenseniin G. B. cereus, L. monocytogenes, and S. aureus were more sensitive to
      jenseniin G when exposed to heat stress than when exposed to cold stress, whereas
      E. coli, Salmonella Typhimurium, and S. flexneri were more sensitive to jenseniin
      G when exposed to cold stress than when exposed to heat stress. When comparing an
      acid stress test alone to a combination of acid stress and jenseniin G, E.
      faecalis and L. monocytogenes showed the greatest sensitivities with 4.87- and
      2.82-log reductions, respectively, after 7 days. All cultures except for S.
      aureus were adversely affected by the combination of salt stress and jenseniin G.
      Salmonella Typhimurium showed the greatest sensitivity to salt stress with
      jenseniin G (a 1.54-log reduction at day 7) when compared to salt stress alone (a
      0.55-log reduction at day 7). Jenseniin G, like bacteriocins produced by other
      gram-positive species, has broader activity against stressed organisms.

PMID- 15151240
TI  - Real-time PCR detection of the thermostable direct hemolysin and thermolabile
      hemolysin genes in a Vibrio parahaemolyticus cultured from mussels and mussel
      homogenate associated with a foodborne outbreak.
AB  - Molecular methods have become vital epidemiological tools in the detection and
      characterization of bacteria associated with a foodborne outbreak. We used both
      culture and real-time PCR to detect a Vibrio parahaemolyticus isolate associated
      with a foodborne outbreak. The outbreak occurred in July 2002 in Polk County,
      Florida, and originated at a Chinese buffet, with one person being hospitalized.
      The hospital isolated V. parahaemolyticus from the patient but destroyed the
      sample after diagnosis. From an onsite visit of the restaurant, food samples that
      possibly contributed to the outbreak were collected and sent to the Florida
      Department of Health, Tampa Branch Laboratory. Crab legs, crabsticks, and mussel
      samples were homogenized and incubated according to the Food and Drug
      Administration Bacteriological Analytical Manual culture protocol. Three sets of
      primers and a TaqMan probe were designed to target the tdh, trh, and tlh genes
      and used for real-time PCR. This study was successful in isolating V.
      parahaemolyticus from a mussel sample and detecting two of its genes (tdh and
      tlh) in food and pure culture by real-time PCR.

PMID- 15151242
TI  - Inactivation of pathogenic bacteria by cucumber volatiles (E,Z)-2,6-nonadienal
      and (E)-2-nonenal.
AB  - The effects of (E,Z)-2,6-nonadienal (NDE) and (E)-2-nonenal (NE) on Bacillus
      cereus, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella
      Typhimurium were investigated. A suspension of each organism of 6 to 9 log CFU/ml
      was incubated for 1 h at 37 degrees C in brain heart infusion solution that
      contained 0 to 500 or 1,000 ppm of NDE or NE. Depending on concentration,
      exposure to either NDE or NE caused a reduction in CFU of each organism.
      Treatment with 250 and 500 ppm NDE completely eliminated viable B. cereus and
      Salmonella Typhimurium cells, respectively. L. monocytogenes was the most
      resistant to NDE, showing only about a 2-log reduction from exposure to 500 ppm
      for 1 h. Conversely, this concentration of NDE caused a 5.8-log reduction in E.
      coli O157:H7 cells. NE was also effective in inactivating organisms listed above.
      A higher concentration of NE, 1,000 ppm, was required to kill E. coli O157:H7, L.
      monocytogenes, or Salmonella Typhimurium compared with NDE. In conclusion, both
      NDE and NE demonstrated an apparent bactericidal activity against these
      pathogens.

PMID- 15151243
TI  - Evaluation of nisin-coated cellulose casings for the control of Listeria
      monocytogenes inoculated onto the surface of commercially prepared frankfurters.
AB  - Commercially prepared frankfurters were formulated with and without approximately
      1.4% potassium lactate and 0.1% sodium diacetate and were subsequently processed
      in cellulose casings coated with and without nisin (approximately 50,000 IU per
      square inch of internal surface area) to control the outgrowth of Listeria
      monocytogenes during refrigerated storage. The frankfurters were inoculated with
      approximately 5 log CFU per package of a five-strain mixture of L. monocytogenes
      and then vacuum sealed before being stored at 4 degrees C for 60 to 90 days.
      Surviving organisms were recovered and enumerated by rinsing each package with 18
      ml of sterile 0.1% peptone water and plating onto MOX selective agar. The data
      for each of two trials were averaged. In packages that contained frankfurters
      formulated with potassium lactate and sodium diacetate and prepared in nisin
      coated casings, L. monocytogenes levels decreased by 1.15 log CFU per package
      after 90 days of storage. L. monocytogenes levels decreased by 0.95 log CFU per
      package in frankfurters that were prepared in casings that were not coated with
      nisin. In packages of frankfurters that were formulated without potassium lactate
      and sodium diacetate and prepared in nisin-coated casings, L. monocytogenes
      levels decreased by 0.88 log CFU per package after 15 days of storage but then
      increased appreciably thereafter over a 60-day period of refrigerated storage.
      There was also an appreciable increase in pathogen numbers during 60 days of
      storage in otherwise similar frankfurters formulated without potassium lactate
      and sodium diacetate prepared in casings that were not coated with nisin. These
      data confirm that potassium lactate and sodium diacetate display listeriostatic
      activity as an ingredient of commercial frankfurters. These data also establish
      that cellulose casings coated with nisin display only moderate antilisterial
      activity in vacuum-sealed packages of commercially prepared frankfurters during
      storage at 4 degrees C.

PMID- 15151244
TI  - Prevalence and growth of Listeria on naturally contaminated smoked salmon over 28
      days of storage at 4 degrees C.
AB  - Only limited data are available on the growth characteristics of Listeria in
      naturally contaminated ready-to-eat foods. To evaluate Listeria contamination
      patterns and growth in smoked salmon, 72 smoked salmon product samples from two
      processing plants were tested for Listeria spp. and L. monocytogenes. Samples
      were divided into four approximately equal portions: one portion was tested on
      receipt, and the other three were vacuum sealed and stored at 4 degrees C for 7,
      14, and 28 days. Listeria testing was performed using both an enrichment
      procedure and direct plating to enumerate Listeria in samples that contained >2
      to 10 CFU/g. Five samples were positive for Listeria spp., including one sample
      that was positive for L. monocytogenes. Most samples yielded only sporadic
      positive results among the portions tested on days 0, 7, 14, and 28. Only one
      sample contained Listeria spp. in numbers above the detection limit for
      enumeration. For this sample, the portions tested on days 7 and 28 contained 46
      and 52 CFU/g, respectively, whereas the portion tested on day 14 was negative.
      Overall, our data indicate that there is considerable heterogeneity in Listeria
      spp. distribution within a single positive smoked fish sample. Even with
      refrigerated storage for 28 days, none of the naturally contaminated samples
      reached Listeria spp. numbers >100 CFU/g, which indicates that Listeria growth
      was limited within a 4-week storage period. However, because of the apparent
      heterogeneity of Listeria distribution within samples, the interpretation of
      growth data collected on naturally contaminated samples is difficult.

PMID- 15151245
TI  - Inactivation of Staphylococcus aureus by pulsed UV-light sterilization.
AB  - Pulsed UV light is a novel technology to inactivate pathogenic and spoilage
      microorganisms in a short time. The efficacy of pulsed UV light (5.6 J/cm2 per
      pulse) for the inactivation of Staphylococcus aureus as suspended or agar seeded
      cells was investigated. A 12-, 24-, or 48-ml cell suspension in buffer was
      treated under pulsed UV light for up to 30 s, and 0.1 ml of sample was surface
      plated on Baird-Parker agar and incubated at 37 degrees C for 24 h to determine
      log reductions. Also, 0.1 ml of cell suspension in peptone water was surface
      plated on Baird-Parker agar plates, and the plates were treated under pulsed UV
      light for up to 30 s. The treated and untreated plates were incubated in the
      conditions described above. A 7- to 8-log CFU/ml reduction was observed for
      suspended and agar-seeded cells treated for 5 s or longer. In the case of
      suspended cells, the sample depth, time, treatment, and interaction were
      significant (P < 0.05). In the case of agar-seeded cells, the treatment time was
      significant (P < 0.05). Our results clearly indicate that pulsed UV technology
      has potential for the inactivation of pathogenic microorganisms.

PMID- 15151246
TI  - Characterization of Bacillus cereus isolates from raw soybean sprouts.
AB  - Raw soybean sprouts, which are used as ingredients in cook-chilled products, were
      analyzed to evaluate the incidence of mesophilic aerobic microorganisms,
      psychrotrophic microorganisms, anaerobic microorganisms, coliforms, and spore
      forming microorganisms Bacillus cereus, Clostridium botulinum, and Clostridium
      perfringens. Mesophilic microorganisms on raw soybean sprouts were present in
      large populations, 5.5 x 10(6) to 1.4 x 10(8) CFU/g, and psychrotrophic
      microorganisms were found to be more numerous than the other groups. Coliforms
      accounted for 15% of mesophilic microorganism counts on average, and the average
      for spore-forming microorganisms was 5.2 x 10(2) CFU/g. B. cereus was isolated
      from 12 of 17 soybean sprout samples, whereas C. botulinum and C. perfringens
      were not isolated. B. cereus was isolated in greater numbers at 30 degrees C
      compared with other temperatures and was not isolated at 4 degrees C. Of the 55
      strains isolated from soybean sprouts, 52 were positive for starch hydrolysis,
      and only 3 strains did not hydrolyze starch. Among the 55 strains of B. cereus
      isolates, 53 showed the ability to produce diarrheal enterotoxin by CRET-RPLA.

PMID- 15151247
TI  - Detection of Bacillus spores using PCR and FTA filters.
AB  - Emphasis has been placed on developing and implementing rapid detection systems
      for microbial pathogens. We have explored the utility of expanding FTA filter
      technology for the preparation of template DNA for PCR from bacterial spores.
      Isolated spores from several Bacillus spp., B. subtilis, B. cereus, and B.
      megaterium, were applied to FTA filters, and specific DNA products were amplified
      by PCR. Spore preparations were examined microscopically to ensure that the
      presence of vegetative cells, if any, did not yield misleading results. PCR
      primers SRM86 and SRM87 targeted a conserved region of bacterial rRNA genes,
      whereas primers Bsub5F and Bsub3R amplified a product from a conserved sequence
      of the B. subtilis rRNA gene. With the use of the latter set of primers for
      nested PCR, the sensitivity of the PCR-based assay was increased. Overall, 53
      spores could be detected after the first round of PCR, and the sensitivity was
      increased to five spores by nested PCR. FTA filters are an excellent platform to
      remove PCR inhibitors and have universal applications for environmental,
      clinical, and food samples.

PMID- 15151248
TI  - Detection of zearalenone and related metabolites by fluorescence polarization
      immunoassay.
AB  - Zearalenone is an estrogenic mycotoxin commonly found in grains throughout the
      world. A number of instrument- and antibody-based methods including enzyme-linked
      immunosorbent assays (ELISAs) have been developed to detect zearalenone (ZEN) and
      related toxins in commodities and foods. Although convenient, the commercial
      ELISAs for small molecules such as ZEN require a washing step to separate bound
      and unbound enzyme label before detection. In fluorescence polarization
      immunoassays, separation of bound and unbound label is not required, a property
      that reduces the time needed to perform the assays. We developed a fluorescence
      polarization immunoassay for ZEN in maize. When combined with a rapid extraction
      technique, the assay could be used to detect as little as 0.11 microg of ZEN g(
      1) maize within 10 min. The assay showed cross-reactivity to the ZEN analogs
      zearalanone, alpha-zearalanol, alpha-zearalenol, beta-zearalenol, and beta
      zearalanol of 195, 139, 102, 71, and 20%, respectively, relative to ZEN (100%).
      Recovery of ZEN from spiked maize over the range of 0.5 to 5 microg g(-1)
      averaged 100.2% (n = 12). The fluorescence polarization immunoassay results were
      comparable to those obtained with a liquid chromatographic method for the
      analysis of 60 naturally contaminated maize samples and maize samples amended
      with culture material. The fluorescence polarization immunoassay provides a rapid
      method for screening of maize for ZEN.

PMID- 15151249
TI  - Effects of pesticides on sporulation of Cyclospora cayetanensis and viability of
      Cryptosporidium parvum.
AB  - Disease outbreaks caused by the coccidian parasite Cyclospora cayetanensis in
      food have been linked to consumption of raspberries that may have been
      contaminated through exposure to water mixed with insecticides and fungicides
      that may have been sprayed onto the berries. Three different fungicides (captan
      50% W.P., benomyl 50% W.P., and zineb 75% W.P.) and two different insecticides
      (malathion 25% W.P. and diazinon 4E 47.5%) were evaluated at five different
      concentrations and for exposure times of 30 min to 1 week. Sporulation of C.
      cayetanensis did not decrease with use of any of the pesticides from time periods
      of 30 min to 24 h at all concentrations. Sporulation percentage was reduced with
      the fungicide benomyl at 1 week of exposure. The growth of the parasite
      Cryptosporidium parvum was also evaluated using captan 50% W.P., benomyl 50%
      W.P., and diazinon 4E 47.5%. Oocyst infectivity was reduced only after 7 days of
      exposure. These results indicate that these pesticides used at recommended
      concentration levels do not affect the sporulation of Cyclospora.

PMID- 15151250
TI  - Dissemination of brain emboli following captive bolt stunning of sheep: capacity
      for entry into the systemic arterial circulation.
AB  - The epidemic of bovine spongiform encephalopathy in the United Kingdom and the
      recognition of a variant of Creutzfeldt-Jakob disease prompted revision of the
      guidelines for slaughter of cattle and sheep to prevent contamination of the
      edible parts of the carcass with central nervous system tissue. We previously
      showed that captive bolt gun stunning, which is routinely used for the slaughter
      of cattle and sheep, causes entry of fragments of central nervous system tissue
      into the jugular vein. To determine whether such tissue can traverse pulmonary
      capillaries to enter the systemic circulation, we introduced small volumes of
      brain tissue that had been disrupted by stunning with a captive bolt gun into the
      jugular vein of sheep sent for slaughter. We examined aortic blood samples by
      immunocytochemistry for neurofilament and S100 proteins and by enzyme-linked
      immunosorbent assay for glial fibrillary acidic protein and found fragments of
      neurofilament- and S100-immunopositive central nervous system tissue in samples
      from 2 of 11 sheep and elevated glial fibrillary acidic protein in 6 sheep. Our
      findings suggest that central nervous system tissue that is dislodged during
      routine captive bolt gun stunning and slaughter of sheep can enter the systemic
      arterial circulation and that, in some cases, this method of slaughter of an
      animal infected with bovine spongiform encephalopathy would be likely to
      contaminate edible parts of the carcass with infective material.

PMID- 15151251
TI  - Quorum sensing: a primer for food microbiologists.
AB  - Quorum sensing is a signaling mechanism through which bacteria modulate a number
      of cellular functions (genes), including sporulation, biofilm formation,
      bacteriocin production, virulence responses, as well as others. Quorum sensing is
      a mechanism of cell-to-cell communication and is mediated by extracellular
      chemical signals generated by the bacteria when specific cell densities are
      reached. When the concentration of the signal (and cell population) is
      sufficiently high, the target gene or genes are either activated or repressed.
      Quorum sensing increases the ability of the bacteria to have access to nutrients
      or to more favorable environmental niches and enhances bacterial defenses against
      eukaryotic hosts, competing bacteria, and environmental stresses. The
      physiological and clinical aspects of quorum sensing have received considerable
      attention and have been studied at the molecular level. Little is known, however,
      on the role of quorum sensing in food spoilage or in the growth and/or toxin
      production of pathogens present in food. A number of compounds have been isolated
      or synthesized that antagonize quorum sensors, and application of these
      antagonists may potentially be useful in inhibiting the growth or virulence
      mechanisms of bacteria in different environments, including food. It is important
      that food microbiologists have an awareness and an understanding of the
      mechanisms involved in bacterial quorum sensing, since strategies targeting
      quorum sensing may offer a means to control the growth of undesirable bacteria in
      foods.

PMID- 15151252
TI  - Trends in characteristics of births by State: United States, 1990, 1995, and 2000
      2002.
AB  - OBJECTIVE: This report presents U.S. and State-level data on births, birth rates,
      fertility rates, sex ratio, marital status, and educational attainment by race
      and Hispanic origin for 1990, 1995, and 2000-2002. METHODS: Data are presented in
      detailed tables, summary tables, maps, and graphs. RESULTS: In 2002 there were
      4,021,726 live births in the United States, 136,486 fewer than in 1990. Despite a
      slight decline in the number of births nationwide, a few States witnessed
      significant increases in the number of live births with most of these States
      located in the western United States. Some of the westward shift in number of
      births is attributable to a growing population and some to the age and race
      composition of the individual States. However, real differences in fertility by
      State persist even when the effects of age structure and race and ethnic
      composition of the States' population are taken into account. This report also
      presents data on sex ratios, percentage unmarried, and educational attainment of
      mothers. Several observations from these data are noteworthy. The proportion of
      births to unmarried mothers increased nationally and in every State between 1990
      and 2002. Nationally the percentage of mothers with fewer than 12 years of
      education fell, and the percentage with 16 or more years increased for all racial
      and ethnic groups. However, at the State level, the percentage of women with
      fewer than 12 years of education increased for nearly a quarter of the States,
      despite near universal increases in the percentage of women with 16 or more years
      of education.

PMID- 15151253
TI  - Management of calcium refilling post-parathyroidectomy in end-stage renal
      disease.
AB  - BACKGROUND: Management of post-parathyroidectomy hypocalcemia in dialysis
      patients is not well defined. We reviewed published approaches to treatment in an
      effort to define a clinical algorithm for controlling serum calcium levels post
      operatively. METHODS: We conducted a PubMed search for the years 1980-2003 with
      the keywords "hypocalcemia" and "parathyroidectomy". Only English language and
      human subject abstracts were analyzed, and only those articles dealing with
      secondary or tertiary hyperparathyroidism (HPTH) were reviewed further. Other
      articles were extracted from cross-referencing. RESULTS: We initially examined
      146 articles. This review summarizes the findings of the relevant articles along
      with our own practice regarding post-parathyroidectomy hypocalcemia management in
      dialysis patients. The vast majority of patients require intravenous (i.v.)
      calcium supplements after surgery. There are no available controlled studies on
      calcium supplementation for post-parathyroidectomy hypocalcemia in this patient
      population. Calcitriol supplementation proved valuable in two studies.
      CONCLUSIONS: Post-parathyroidectomy hypocalcemia is a common complication, which
      can be prevented and treated with oral and i.v. calcium supplementation and/or
      active vitamin D metabolites. Daily follow-up of both serum calcium and
      phosphorus are mandatory to prevent this major post-operative complication. Based
      on the available evidence, we propose a protocol for the prevention and treatment
      of post-parathyroidectomy hypocalcemia, for use in clinical practice. This
      approach requires validation by a controlled clinical trial.

PMID- 15151254
TI  - New immunosuppressive strategies in renal transplant recipients.
AB  - Along with expanded knowledge of pathophysiological processes involved in
      transplant rejection, a variety of immunosuppressive agents with very specific
      modes of action have been developed. The focus of this review is an update on the
      pathophysiologic rationale and experience with such agents in human renal
      transplantation that are currently clinically available or are under
      investigation in human trials. Clinical data are reviewed with respect to
      calcineurin inhibitor sparing regimens based on mycophenolate or sirolimus, the
      use of leflunomide and its derivative FK778, modulation of chemotaxis with FTY720
      or chemokine receptor blockers and the results of costimulatory blockade. While
      selection of one of these strategies may allow a more individualised therapy, the
      immunosuppressive potential of each compound has to be weighed against adverse
      reactions for an individual patient.

PMID- 15151255
TI  - Vascular access for hemodialysis: the impact on morbidity and mortality.
AB  - BACKGROUND: In chronic hemodialysis (HD), central venous catheter (CVC) use seems
      associated with an increased risk of death. This study, using registry data,
      evaluated the morbidity and mortality risk associated with the use of different
      permanent vascular access (VA) in a HD patient cohort. METHOD: We evaluated
      hospitalization and death rate in prevalent and incident HD patients recorded in
      the uremic registry of Campania (southern Italy) for 2001. Patients were divided
      into three groups: CVC, artero-venous graft (AVG) and artero-venous fistula
      (AVF). RESULTS: One hundred and eleven dialysis units in the Campania region
      (69%) provided data. A total of 2201 out of 3387 prevalent HD patients were
      included: 92 patients (4.2%) were on CVC, 24 patients (1.1%) were on AVG and 2085
      patients (94.7%) were on AVF. In comparison with AVF, the CVC group had a greater
      prevalence of female gender, old age, diabetes, comorbidities, hypoalbuminemia,
      anemia, erythropoietin (EPO) resistance, and less frequent synthetic membrane
      use, but had a similar dialysis duration (hr/week). Similar data were collected
      in the 635 incident patients registered in 2001. During the study, in both
      prevalent and incident CVC patients, either hospitalization or death rates were
      enhanced; however, the difference in the relative risk (RR) of death disappeared
      after correction for age, gender, malnutrition, diabetes, hemoglobin, albumin and
      comorbidity. Among incident patients, survival analysis was performed in patients
      remaining on the same VA type throughout the follow-up period; while a similar
      survival between groups was demonstrated in the 1st year of follow-up, survival
      was worse in the CVC group during the 2nd year of follow-up; however, this
      difference also disappeared in the adjusted analysis. CONCLUSION: This cohort
      study demonstrates that in chronic dialysis patients CVC choice, with respect to
      AVF, is mainly associated with female gender, advanced age and worse clinical
      conditions at baseline, and a worst outcome in both prevalent and incident CVC
      patients compared to AVF patients. Hospitalization, mortality rate and RR of
      death increased significantly; however, differences disappeared after correction
      for comorbidity. Therefore, these data suggest that CVC use per se is not
      associated with increased mortality risks with respect to AVF.

PMID- 15151256
TI  - Death-associated protein kinase localization to human renal tubule cells, and
      increased expression of chronic obstructive uropathy in rats.
AB  - BACKGROUND: Death-associated protein kinase (DAP kinase) is a Ca2+/calmodulin
      dependent serine/threonine kinase implicated as a positive apoptosis mediator.
      However, little is known about DAP kinase involvement with apoptosis in renal
      diseases. METHODS: In order to determine whether DAP kinase has a role in renal
      cell apoptosis in kidney diseases, we performed an immunohistochemical study
      using a monoclonal antibody to DAP kinase. Firstly, by examining the cellular
      distribution of DAP kinase in normal human renal tissues and cultured proximal
      tubule cells. We then used western blotting and immunohistochemical analysis to
      examine directly whether DAP kinase protein levels could be modulated in rat
      kidneys with chronic obstructive uropathy created by unilateral ureteric
      ligation. RESULTS: Immunohistochemistry of normal human kidney tissues showed
      that DAP kinase was exclusively localized in the cytoplasm of renal tubule cells.
      Expression analysis of DAP kinase using cultured cells confirmed DAP kinase mRNA
      and protein presence in human renal tubule cells. Immunocytochemical analysis
      directly visualized DAP kinase in the cytoplasm of the renal tubule cells in
      culture. Finally, DAP kinase was found up-regulated in renal tubule cells of rat
      kidneys with chronic obstructive uropathy. CONCLUSIONS: Our study demonstrates
      that DAP kinase is localized to renal tubule cells, implying a crucial role for
      DAP kinase in renal tubular cell apoptosis in progressive renal diseases.

PMID- 15151257
TI  - Sodium dicarboxylate cotransporter-1 expression in renal tissues and its role in
      rat experimental nephrolithiasis.
AB  - BACKGROUND: Nephrolithiasis is a common disease with a high recurrence rate;
      however, calcium stone pathogenesis remains unknown because of complex multiple
      factors. Hypocitraturia induced by citrate transport disturbance is known to be
      involved in nephrolithiasis development. Sodium dicarboxylate cotransporter
      (NaDC) mediates citrate uptake from the renal proximal tubule. However, the role
      of NaDC in nephrolithiasis is unclear. This study aimed to investigate NaDC-1
      expression in rat renal proximal tubule epithelial cells and its relationship
      with experimental nephrolithiasis. METHODS: Male Wastar rats were divided into
      control, ethylene glycol (EG)-treated and potassium citrate-treated groups.
      Calcium oxalate (CaOx) crystal deposition and histological changes in the kidneys
      were examined with anatomical and light microscopes. The plasma and urinary
      biochemical parameters, such as citrate, oxalate etc, were analyzed by routine
      biochemical methods. NaDC-1 mRNA expression in kidneys was determined by northern
      blot analysis, the change in NaDC-1 protein abundance was detected by
      immunohistochemistry. RESULTS: It was found that NaDC-1 expression and its mRNA
      significantly increased in the EG group when compared with controls. Increased
      NaDC-1 expression was associated with a decline in urinary citrate excretion.
      Potassium citrate administration could significantly down-regulate NaDC-1
      expression and its mRNA, and elevate urinary citrate content alleviate renal
      pathological changes and reduce nephrolithiasis occurrence. CONCLUSION: Increased
      NaDC-1 expression on the renal proximal tubule epithelial cells could play an
      important role in nephrolithiasis development, suggesting it could be a
      therapeutic target for the treatment of nephrolithiasis.

PMID- 15151258
TI  - Extracorporeal management of valproic acid overdose: a large regional experience.
AB  - BACKGROUND: Valproic acid intoxication is common in North America. Although extra
      corporeal therapy has been proposed as beneficial in managing significant
      exposures, evidence to support its use is limited to isolated case reports. A
      systematic review has not been performed. METHODS: All cases of valproic acid
      overdose in Ontario, Canada, reported to the Hospital for Sick Children Poison
      Information Centre (PIC) between January 1st and July 31st 2002 were reviewed.
      Patients with valproic acid levels > 100 microg/mL were divided into two groups:
      those treated with and without extra-corporeal therapy. All hospital-measured
      valproic acid levels and additional clinical information including elimination
      half-life and clearance were obtained for patients treated with extra-corporeal
      therapy. RESULTS: There were 28,362 calls to the PIC, of which 139 related to
      valproic acid poisoning. Thirty-two patients had peak levels > 100 microg/mL. 26
      patients were managed conservatively and 6 with extra-corporeal therapy. Survival
      was 100% in both groups. Patients who received extra-corporeal therapy had higher
      peak levels (p=0.005), were more frequently treated with charcoal (P=0.006),
      required intensive care admission (P=0.019), intubation (P<0.001), and
      vasopressors (P=0.004). Valproic acid elimination was enhanced about tenfold
      through extra-corporeal methods. Complications included tonic-clonic seizures in
      1 patient who received hemodialysis, and thrombocytopenia in 1 patient who
      underwent hemoperfusion. CONCLUSION: Hemodialysis and hemoperfusion are safe,
      effective adjuncts in the management of serious valproic acid intoxication and
      should be considered for patients with hemodynamic or neurological instability.
      Further study is needed to determine whether hemodialysis alone versus combined
      hemodialysis-hemoperfusion is more effective for this condition.

PMID- 15151259
TI  - Acute spontaneous tumor lysis presenting with hyperuricemic acute renal failure:
      clinical features and therapeutic approach.
AB  - BACKGROUND: Acute spontaneous tumor lysis syndrome (STLS) presenting with
      hyperuricemic acute renal failure (ARF) is a rare disease which can be overlooked
      in patients with neoplasic disorders, requiring prompt recognition and aggressive
      management. This study examined the incidence, clinical characteristics and
      prognosis of this condition. METHODS: A retrospective study was performed,
      reviewing the records of all patients who developed ARF at Chang Gung Memorial
      Hospital between 1st July 1999 and 30th October 2002. Acute STLS was diagnosed
      based on pretreatment hyperuricemic ARF, ratio of urinary uric acid to creatinine
      (Cr) >1.0, and significantly elevated lactate dehydrogenase (LDH) (>500 units/L),
      together with a pathologically proven malignancy. Clinical course, metabolic
      parameters, response to therapeutics and outcome were assessed in all patients.
      RESULTS: STLS-induced acute uric acid nephropathy was identified in 10 out of 926
      ARF patients (1.08%) studied. Most presentations were non-specific or related to
      malignancy symptoms. All patients had advanced tumors with large tumor burden,
      and abdominal organ involvement in 80% of patients. The 10 hyperuricemic patients
      became oliguric despite conservative therapy, and remained hyperuricemic (mean +/
      SD: 20.7 +/- 5.0 mg/dL) until dialysis initiation. Seven patients (70%)
      developed diuresis, with an associated resolution of hyperuricemia, azotemia and
      metabolic derangements following dialysis initiation. The patients who developed
      diuresis had mean serum uric acid levels 9.3 +/- 3.1 mg/dL and median levels 9.8
      mg/dL. Three patients (30%) survived, with two patients suffering residual renal
      function impairment. CONCLUSIONS: Acute STLS presenting with hyperuricemic ARF is
      a rare cause of acute uric acid nephropathy in patients with bulky or occult
      neoplastic disorders. The tumors that developed STLS had advanced stage or large
      tumor burden. Frequent abdominal organ involvement and non-specific initial
      presentations can obscure the nature of the disease and delay diagnosis. Unlike
      hyperuricemia and oliguria, which are constant findings, azotemia or impaired
      renal function is not always manifest on initial presentation. Poor outcomes in
      patients with STLS developing acute uric acid nephropathy make early recognition,
      aggressive management and prompt dialysis mandatory.

PMID- 15151260
TI  - Three-dimensional contrast-enhanced magnetic resonance angiography (3-D CE-MRA)
      in the evaluation of hemodialysis access complications, and the condition of
      central veins in patients who are candidates for hemodialysis access.
AB  - BACKGROUND: Arteriovenous (AV) fistulas are crucial in patients requiring long
      term hemodialysis (HD). Dysfunctions of these fistulas are the most common causes
      of recurrent hospitalizations. This study aimed to evaluate the feasibility,
      safety and usefulness of contrast-enhanced magnetic resonance angiography (CE
      MRA) in the evaluation of HD fistulas complications, and the condition of the
      central veins before HD access. METHODS: This study comprised 30 consecutive
      patients (15 females, 15 males; age range 25-66 yrs, mean +/- SD 51.2 +/- 9.9
      yrs). Of 30 patients, 26 had native AV fistulas and the remaining four patients,
      who had a history of previous subclavian vein catheterization, were candidates
      for HD fistulas. Nine patients had a radiocephalic fistula, 15 had a
      brachiobasilic fistula, one had a saphenous vein graft, and one had
      brachiobasilic vein transposition. To observe the fistula complications in these
      cases, three-dimensional (3-D) CE-MRA using gadolinium was performed. RESULTS:
      The results were considered normal in three patients (10%), who were candidates
      for AV fistula construction; one patient had central vein occlusion due to
      previous catheterization. Thirteen patients (43.3%) had venous stenosis or
      occlusion; three of them (10%) had low CE arteries distal to fistula region,
      leading to ischemic complications, and six (20%) had stenosis at the fistula
      region. Seven patients (23.3%) had venous pseudoaneurysms, whereas two of them
      had both pseudoaneurysms and fistula region stenosis, and one had both venous
      stenosis and pseudoaneurysm. There were no adverse or allergic-like reactions or
      heat and taste sensations observed in our series. CONCLUSIONS: 3-D CE-MRA is a
      useful, safe and a practical imaging modality in complicated fistula diagnosis
      with fewer complications and side-effects in comparison to fistulography.

PMID- 15151261
TI  - The Diamant Alpin Dialysis cohort study: clinico-biological characteristics and
      cardiovascular genetic risk profile of incident patients.
AB  - BACKGROUND: Clinical and therapeutic characteristics of chronic dialysis patients
      vary widely at national and/or regional levels. Their increased cardiovascular
      (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk
      factors only. Therefore, this study aimed to investigate and compare the
      characteristics of patients starting dialysis in a homogeneous Alpin region and
      possibly to identify new biological parameters (phenotypes or genotypes), which
      eould be responsible for the increased CVD seen in end-stage renal disease (ESRD)
      patients. METHODS: A cohort of 279 non-selected consecutive patients entering a
      dialysis program was prospectively investigated in eight centers of three
      adjacent regions in France, Italy and Switzerland. In addition to the usual
      demographic, clinical and biological data, we analyzed at study entry the blood
      levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density
      lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin
      phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting
      enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen
      activator inhibitor-1 (PAI-1) genetic polymorphism. RESULTS: At entry, 90.3% of
      patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were
      current smokers; 42% of patients had already experienced at least one CV event:
      peripheral artery disease (26% of the cohort), coronary artery disease (22%) or
      ischemic cerebro-vascular disease (16%). Forty-two patients had had > or =2 CV
      events or documented atherosclerotic localizations. Anemia was not optimally
      treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients
      received erythropoietin (EPO) prior to dialysis, large national differences were
      observed. Compared to the reference population, ESRD patients exhibited increased
      homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the
      distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent
      to that of the reference population. In addition, none of the analyzed
      phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype,
      could be associated with the existence of a previous adverse CV event.
      CONCLUSIONS: (1) The clinical characteristics of the ESRD patients entering
      dialysis in our region were comparable to the currently observed dialysis
      populations in most European countries with the deleterious role of advancing
      age, diabetes, previous CVD, smoking and hypertension evident (2). Except for
      anemia therapy, there were no regional or national differences observed at
      dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors
      demonstrated differences with the reference population only for
      hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable
      differences among the participating centers.

PMID- 15151262
TI  - Home hemodialysis a la carte: a tailormade program (1998-2003).
AB  - BACKGROUND: There are good epidemiological (increased numbers of dialysis
      patients), economical (renal replacement therapy (RRT) costs) and clinical
      reasons (new highly efficient schedules) to reconsider the choice of home
      hemodialysis (HD). STUDY AIM: Analysis of the results and costs of a flexible,
      tailormade home dialysis program (1998-2003). SETTING: Home HD facility of the
      University of Turin-Italy. METHODS: Results were analyzed in terms of feasibility
      (enrolment rate, logistical problems--the two usual caregivers performed a
      retrospective analysis of the clinical records; production costs, assessed with a
      logic bottom-up technique). Since the main program feature was the tailoring of
      dialysis to the patient, kinetic data were analyzed to control the efficiency of
      the chosen schedules. RESULTS: In 1998-2003 (54 months), 31 patients joined the
      home HD program (six patients were already being treated), while another 12
      patients were treated in the training area and trained for an ongoing self-care
      program; mean age was 47.1 +/- 12.8 yrs; 35/49 patients had clinical
      comorbidities. During the study, four patients died, 10 were grafted, and six
      patients dropped out or were transferred. In March 2003, 23 patients were at
      home/in training and six were being treated in the training area: 11 patients
      were on a conventional schedule, four on daily dialysis, 12 on other schedules
      (two patients non-resident in the Piedmont region were not considered). Dialysis
      efficiency reached the target (EKRc > 11 mL/min) in all but four patients
      (schedules with more frequent sessions were planned for these patients). Costs
      were comparable to limited care HD (daily: 96.5 euros/session at home, 98.76
      euros/session in the center; conventional: 133.48 euros/session at home, 131.25
      euros/session in the center). CONCLUSION: A tailored, flexible policy can help to
      revive a home HD program.

PMID- 15151263
TI  - Effects of 12 months of recombinant growth hormone therapy on parameters of bone
      metabolism and bone mineral density in patients on chronic hemodialysis.
AB  - BACKGROUND: Renal osteodystrophy is common in patients with chronic renal failure
      (CRF) on hemodialysis (HD), leading to reduced bone mineral density (BMD) and
      higher bone fracture incidences. Since growth hormone (GH) and insulin-like
      growth factor 1 (IGF-1) are known to enhance bone metabolism and BMD, and CRF
      patients exhibit GH and IGF-1 resistance, recombinant human GH (rhGH) therapy
      could be beneficial for these patients. METHODS: This study evaluated the effects
      of a 12-month rhGH therapy on bone metabolism parameters; alkaline phosphatase
      (AP), osteocalcin (OC), procollagen I carboxyterminal propeptide (PICP),
      telopeptide ICTP, serum crosslaps, n-terminal propeptide of type III procollagen
      (PIIINP) and intact parathyroid hormone (iPTH), as well as on BMD of the lumbar
      spine and the femoral neck in 19 malnourished HD patients (10 females, 9 males)
      with a mean age of 59.3 +/- 13.4 yrs. Fourteen patients completed the 12-month
      study. RhGH (0.25 IU/kg) was given subcutaneously 3x/week after each dialysis
      session. RESULTS: IGF-1 concentrations rose significantly from 169.2 +/- 95.6 to
      262.9 +/- 144.4 ng/mL (p<0.01) after 3 months, followed by a slight decline over
      the next 9 months. PICP as a bone formation marker significantly increased after
      3 months from 250.1 +/- 112.6 to 478.5 +/- 235.2 ug/L (p<0.01), as well as
      PIIINP, whereas OC and bone resorption parameters like ICTP showed only a slight
      increase (ICTP: 50.3 +/- 18.5 to 70.0 +/- 39.5 ug/L after 3 months (ns)). All
      bone metabolism parameters slightly declined in the following 9 months, but
      remained above baseline values after 12 months. PTH rose from 198.0 +/- 139.2 to
      456.0 +/- 268.7 ng/ml, p<0.01 after 6 months. BMD of the lumbar spine showed a
      significant reduction after 3-month rhGH therapy (0.80 +/- 0.17 vs. 0.77 +/- 0.16
      g/cm2, p<0.01), but returned to baseline values after 12 months. BMD of the
      femoral neck remained stable during the entire study. CONCLUSIONS: In summary, 12
      month rhGH treatment in patients on chronic HD caused a significant increase in
      IGF-1, together with an increase in bone turnover. In addition, there was a
      temporary reduction in BMD of the lumbar spine seen, which returned to baseline
      values after 12 months.

PMID- 15151265
TI  - Loss of captopril-bound Fe by end-stage renal failure patients during
      hemodialysis.
AB  - BACKGROUND: Patients on chronic hemodialysis often suffer from severe anemia, the
      outcome of iron deficiency and inadequate response to erythropoietin.
      Antihypertensive treatment with captopril worsens anemia, erythropoietin
      production and iron balance in hemodialysis patients. We investigated the
      possibility that iron chelation by captopril in the blood may result in
      elimination of iron-captopril complexes during hemodialysis, thus minimizing the
      effect of both medications. METHODS: Twelve hypertensive hemodialysis patients
      (group 1) were treated with 12.5 mg/day captopril, while their 12 counterparts
      received 1.25 mg/day ramipril. Following two weeks of treatment and two weeks of
      "washout", captopril in group 1 was substituted with ramipril and ramipril in
      group 2 was replaced by captopril for an additional two week period. Blood and
      dialysate samples were procured at the beginning and the end of the dialysis, for
      iron, aluminum, transferin, ferritin, hemoglobin (Hb) and hematocrit (Htc)
      determination. RESULTS: Iron, ferritin, transferin, Hb and Htc were decreased in
      the captopril-treated group 1. They similarly decreased in group 2 following
      replacement of ramipril by captopril for an additional period of two weeks.
      Significant amounts of iron were detected in dialysates of captopril, but not
      ramipril-treated patients. At the end of the dialysis, iron content was further
      increased in dialysates of the captopril-treated groups. CONCLUSIONS: 1)
      Captopril-chelated iron is eliminated in dialysis fluid during the dialysis
      session, apparently contributing to captopril-related anemia in patients on
      chronic hemodialysis. 2) Antihypertensive treatment with angiotensin converting
      enzyme (ACE) inhibitors other than captopril might prove advantageous for this
      patient category.

PMID- 15151264
TI  - High doses of intravenous calcitriol in the treatment of severe secondary
      hyperparathyroidism.
AB  - BACKGROUND: In hemodialysis (HD) patients, secondary hyperparathyroidism (HPTH)
      is a severe common disease. Calcitriol administration has been demonstrated as an
      effective therapy. In this prospective study, our aim was to determine the
      necessary calcitriol dose required to control severe HPTH preventing
      hypercalcemia or hyperphosphatemia and avoiding parathyroidectomy. METHODS:
      Eighteen dialysis patients suffering from severe HPTH during a 12-month period
      received intravenous (i.v.) calcitriol pulse doses (2-8 mcg/3x/week). Multislice
      helical computed tomography (CT) cardiac imaging was performed to measure
      coronary artery calcifications. RESULTS: Fourteen patients showed an improvement
      (parathyroid hormone (PTH) level < 400 pcg/mL), one patient an incomplete
      reduction, and three patients starting from PTH levels between 1100 and 2386
      pcg/mL did not appear to benefit from the therapy. After a 6-month therapy in
      15/18 patients PTH levels were significantly lower (p<0.05). In a large portion
      of the group, as well as in the control group, coronary calcification values were
      high when compared to the normal range. CONCLUSIONS: According to our data, we
      concluded that severe HPTH could be treated successfully by i.v. calcitriol pulse
      doses reaching high doses (up to 8 mcg/3x/week) and for a prolonged period of
      time (6 months). In such cases, close monitoring is necessary to prevent
      hyperphosphatemia and hypercalcemia episodes.

PMID- 15151266
TI  - The relationship between reticulocyte hemoglobin content with C-reactive protein
      and conventional iron parameters in dialysis patients.
AB  - Adequate iron stores are a prerequisite for successful erythropoietin (EPO)
      therapy in hemodialysis (HD) patients. Nevertheless, iron status estimation in HD
      patients remains problematic, as most parameters are influenced by inflammation.
      The reticulocyte hemoglobin content (CHr) has recently been proposed as a useful
      tool in iron status assessment. However, the effect of inflammation on CHr
      remains unstudied. This study aimed to assess the relationship between CHr with
      other parameters of iron status as well as with C-reactive protein (CRP). This
      relationship was studied in all the patients (n=61) at our dialysis unit. CHr was
      significantly and positively related to transferrin saturation (TS) (rho=0.26;
      p<0.05) and inversely to the percentage of hypochromic red blood cells (%Hypo)
      (rho=-0.63; p<0.0001), but not to serum ferritin. CHr was strongly and inversely
      related to log CRP (rho=-0.50; p<0.0001). Despite the use of maintenance
      intravenous (i.v.) iron doses and relatively high serum ferritin levels, a large
      percentage of patients were in a state of functional iron deficiency (%Hypo > or
      = 6 in 41% of patients and CHr < or = 29 pg in 13% of patients). This percentage
      was far lower in patients with CRP levels below the detection limit (2 mg/L) (26%
      and 0%, respectively). In conclusion, CHr is related to both TS and %Hypo, but
      not to serum ferritin, and is strongly influenced by the presence of inflammation
      (as determined by CRP). In patients with elevated CRP levels, it is very
      difficult to reach target iron status levels without exceeding the upper limits
      for serum ferritin.

PMID- 15151267
TI  - Type 2 diabetes in patients with end-stage renal disease is not associated with
      further increased serum inflammatory parameters.
AB  - BACKGROUND: Cardiovascular morbidity and mortality is markedly increased in
      patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and is
      further pronounced when diabetes mellitus is also present. As atherogenesis is
      mediated by inflammation of vessel walls and as evidence evolves that
      atherosclerosis and diabetes mellitus share a common inflammatory basis, we
      considered whether ESRD patients with additional diabetes mellitus exhibit
      increased inflammation levels exceeding those of ESRD patients without diabetes
      mellitus. METHODS: The study included 20 ESRD patients with type 2 diabetes
      mellitus and 16 non-diabetic ESRD patients on long-term HD. The patients'
      clinical characteristics and serum levels of C-reactive protein (CRP),
      interleukin 6 (IL-6), soluble tumor necrosis factor receptor I (sTNF-RI),
      neopterin and fibrinogen were assessed. RESULTS: There were no significant
      differences in serum levels of CRP, IL-6, neopterin, sTNF-RI and fibrinogen found
      in ESRD patients with and without diabetes mellitus. HD duration correlated
      significantly with neopterin (r=0.515, p<0.001) and sTNF-RI (r=0.429, p<0.05)
      serum levels. HD led to a significant reduction in neopterin levels whereas CRP,
      IL-6 and sTNF-RI levels did not change significantly. CONCLUSIONS: With the
      inherent limitations of a small number of patients studied, we observed that the
      presence of type 2 diabetes mellitus in addition to ESRD was not associated with
      further increased serum levels of the examined inflammatory parameters. Our
      observations suggest that the worsened prognosis of diabetic ESRD patients is
      probably not explainable by superimposing inflammatory processes.

PMID- 15151269
TI  - Secondary IgA nephropathy presenting as nephrotic syndrome with glomerular
      crescentic changes and acute renal failure in a patient with autoimmune
      hepatitis.
AB  - Patients with end-stage liver disease are prone to hemodynamic and immunologic
      renal injury, the latter at times manifesting as glomerulonephritis. Elevated
      serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in
      these patients, but are often clinically silent. We report a patient with
      autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with
      nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli
      having undergone crescentic change, and with IgA2 deposits in the glomerular
      mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic
      management.

PMID- 15151268
TI  - Inflammation and coronary calcification in renal patients--factors that may
      explain increased cardiovascular risk, and poorer results of coronary
      interventions?
AB  - Cardiovascular disease (CVD) is one of the major causes of mortality in patients
      with renal diseases, with increased odds ratio of mortality with risk factors as
      diverse as cholesterol, vascular stiffness, chronic inflammation and
      hyperhomocysteinemia. Several factors have been incriminated to explain the
      increase in coronary vascular calcification (CVC) in this particular population.
      Increased duration of dialysis, dyslipidemia, altered calcium-phosphorus
      metabolism, and chronic inflammation have all been associated with increased CVC.
      We present here four case reports illustrating the differences in the
      pathophysiology, therapy and prognosis of calcific coronary heart disease seen in
      uremic patients.

PMID- 15151270
TI  - Post-reperfusion rapidly progressive glomerulonephritis in post-transplant IgA
      nephropathy.
AB  - Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA
      nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy.
      RPGN post ischemia-reperfusion has not been previously reported. We report a 62
      year old male patient on azathioprine therapy, 9 years after left cadaveric renal
      transplantation due to end stage renal disease of unknown etiology, who presented
      with progressive deterioration in renal function and hematuria. Renal biopsy was
      consistent with IgAN. Duplex and CT scan demonstrated a decreased renal graft
      perfusion, due to severe atherosclerosis and stenosis of iliac arteries. The
      patient underwent left axilo-femoral bypass graft surgery with improvement in
      kidney graft perfusion and function. However, few weeks later, patient presented
      with pulmonary edema and advanced renal failure and he was initiated on
      hemodialysis. Repeated renal biopsy demonstrated crescentic GN. To the best of
      our knowledge, this is the first report of RPGN following reversal of ischemia
      and reperfusion. There was no evidence for atherembolic disease which is not
      uncommon after vascular surgery and it has been reported to be rarely associated
      to crescentic GN. Theoretical explanations for exacerbation of IgAN to crescentic
      GN, following successful reperfusion, could be enhancement of capillary damage,
      inflammation and oxidative stress. Putative mechanisms for these phenomena may be
      interaction of reperfusion-induced hyperfiltration, high intraglomerular
      capillary pressure, oxidative stress, increased polymorphonucler cells
      infiltration and inflammation; the presence of IgA immune deposits and
      azathioprine metabolites, both can also be associated to enhancement of oxidative
      stress.

PMID- 15151272
TI  - Focal and segmental glomerulosclerosis (FSGS). Clinical, morphological and
      genetic features.

PMID- 15151271
TI  - Recurrent membranous nephropathy and leiomyosarcoma in the renal allograft of a
      lupus patient.
AB  - The frequency of membranous lupus nephritis recurrence (World Health Organization
      (WHO) class V) in the allograft after renal transplantation is unknown, but it
      appears uncommon (only two reported cases in the literature). Despite the
      increased incidence of sarcomas in organ transplant recipients (compared to the
      general population), non-Kaposi's sarcoma is an uncommon malignancy, and primary
      tumor involvement of a renal allograft is a rare occurrence. Our patient is a 28
      year old female with end-stage renal disease (ESRD) secondary to membranous lupus
      nephritis who received a living related transplant from her mother. At 26 months
      post-transplant, she presented with proteinuria and a rise in creatinine (Cr).
      Allograft biopsy was consistent with recurrent membranous nephropathy. Five weeks
      later, she was found to have a high-grade leiomyosarcoma originating within the
      allograft. We reviewed the literature on recurrent post-transplant membranous
      nephropathy and the possible role of the Epstein-Barr virus (EBV) infection in
      smooth muscle tumors occurring in organ transplant recipients. We also considered
      the association of membranous nephropathy and malignancy.

PMID- 15151273
TI  - Homer W. Smith's contribution to renal physiology.
AB  - Homer Smith was, for three decades, from the 1930s until his death in 1962, one
      of the leaders in the field of renal physiology. His contributions were many: he
      played a major role in introducing and popularizing renal clearance methods,
      introduced non-invasive methods for the measurement of glomerular filtration
      rate, of renal blood flow and tubular transport capacity, and provided novel
      insights into the mechanisms of excretion of water and electrolytes. Homer
      Smith's contributions went far beyond his personal investigations. He was a
      superb writer of several inspiring textbooks of renal physiology that exerted
      great and lasting influence on the development of renal physiology. Smith's
      intellectual insights and ability for critical analysis of data allowed him to
      create broad concepts that defined the functional properties of glomeruli,
      tubules and the renal circulation. A distinguishing feature of Homer Smith's
      career was his close contact and collaboration, over many years, with several
      clinicians of his alma mater, New York University. For initiating these
      pathophysiological investigations, he is justly credited to have advanced, in a
      major way, our understanding of altered renal function in disease. Smith's
      lasting scientific impact is also reflected by a whole school of investigators
      that trained with him and who applied his methods, analyses and concepts to the
      study of renal function all over the world. So great was his influence and
      preeminence that Robert Pitts, in his excellent tribute to Homer Smith in the
      Memoirs of the National Academy of Science states that his death brought an end
      to what might be aptly called the Smithian Era of renal physiology.

PMID- 15151274
TI  - The development of the clearance concept.
AB  - The clearance concept is central to three critical areas of nephrology; it was a
      key feature to early conceptual analysis of the nature of urine formation, it was
      utilized as a measure of kidney function in advancing renal diseases, and it was
      a pivotal concept to elucidate the physiology of the kidneys. This paper
      describes the clearance concept as currently understood and then it examines how
      clearance was utilized to understand these various aspects of kidney function.

PMID- 15151275
TI  - Rokitansky and his first description of polyarteritis nodosa.
AB  - Karl Rokitansky, Professor of Pathology at the University of Vienna described
      polyarteritis nodosa in 1852 in a 23 year old man with a 5-day history of fever
      and diarrhoea.

PMID- 15151276
TI  - Jakub Penson and his studies on acute renal failure during typhus epidemics in
      Warsaw Ghetto.
AB  - In the Warsaw Ghetto established by the German Nazis as a special district for
      Polish Jews in 1940 there were two typhus epidemics. Many patients affected by
      this disease (1500 during the first and 6500 during second epidemic) were treated
      at The Department of Infectious Disease of Czyste Hospital headed by Dr Jakub
      Penson--a Polish physician of Jewish origin. A heroic group of 20 physicians not
      only treated patients in these tragic circumstances, but also performed in
      defiance of Nazi prohibition, scientific studies on the clinical course of typhus
      with special attention on hyperazotemia and renal complication. The results of
      their observations were presented in 1941-42 during clinical meetings in Czyste
      Hospital and later published by Penson in 1946 in the Polish Physicians Weekly.
      Among other clinical statements a description of acute renal failure of
      extrarenal origin, caused by dehydration and toxic influence of primary disease
      seems the most important one. It has to be taken into account that acute renal
      failure appearing during Crush Syndrome was described by Bywaters in 1941. Jakub
      Penson survived the German Nazi occupation and later become a head of the
      Internal Medicine Department in Gdansk Medical University and one of the
      precursors of clinical nephrology in Poland.

PMID- 15151277
TI  - History of fluid balance and kidney function in space.
AB  - During the last four decades, about 400 people have been in Space, since Yuri
      Gagarin was sent in 1961 as the first human into Earth orbit. From the very
      beginning, the circulatory system of astronauts (meaning heart, vascular system,
      body fluid distribution and balance, and the kidney) was central to the medical
      concerns of Space physiologists and physicians because of its gravity-dependence.
      The present manuscript puts emphasize on some key scientists who worked in the
      field of body fluid regulation and kidney function in the USA, in Russia and in
      Europe during recent decades. The manuscript in particular summarizes the outcome
      of this research and describes the present understanding of how the body fluid
      regulatory system adapts to the extreme environment of Space.

PMID- 15151278
TI  - Experiences and perspectives for the use of a Paenibacillus strain as a plant
      protectant.
AB  - A study on the microbial ecology in an active slow sand filter, used for
      disinfecting the circulating plant nutrient solutions, showed that spore-forming
      plant-associated bacteria belonging to the Bacillus-Paenibacillus complex are
      well adapted for transmission in the solutions and passage through the filter.
      Therefore, strains from this bacterial group were suitable candidates for
      biological control in irrigated and closed plant growth systems. The spore
      forming Paenibacillus polymyxa strain PpDGB was selected in in vitro tests as a
      potent pathogen-antagonist and was tested as a prophylactic protection agent in
      the plant rhizosphere, especially for cultures stages that are highly susceptible
      to stress and disease. Plant cuttings, in vitro plants and seeds of different
      plant types were bacterized and planted in their typical disease-conducive
      environment where nutrient solutions or water irrigation was applied and further
      plant development was monitored. Observed plant parameters were plant survival,
      weight, chlorophyll concentration in the leaf mesophyl, root health and root hair
      formation. The PpDGB treatment initially induced stress in the plants, which was
      observed as a transient stop in plant transpiration. This effect caused some
      necrosis in the most stress-sensitive in vitro plant species. In the other plants
      this stress period was followed by a significant enhancement in plant growth. In
      case of seed treatment, more seeds germinated and seedling growth was faster. In
      the tested formulation, PpDGB enhanced growth but not disease resistance,
      probably due to simultaneous activation of the residual plant pathogens.
      Therefore variant formulations have to be tested. The influence of PpDGB on the
      composition of the bacterial communities in the rhizosphere was assessed by DGGE
      profiling. In soilless plant cultures, PpDGB-driven profile changes could be
      observed from the 5th day after the initial treatment. P. polymyxa bacteria were
      shown to be widely present in association with plants and specific PpDGB
      detection in plant and rhizosphere was only possible with newly developed strain
      specific PCR primers based on Nif H gene sequences. Quantitative PCR based on
      SYBR Green fluorescence enabled detection of low PpDGB concentrations in the
      plant rhizosphere.

PMID- 15151279
TI  - Evaluation of Trichoderma spp. for biocontrol of tomato sudden caused by Pythium
      aphanidermatum following flooding in tropical hot season.
AB  - Tomato sudden death is a major problem in tomato production in tropical lowland
      areas. The plant wilts and dies following artificial or natural flooding for 48
      72 hrs in the summer season. Occurrence of this disease is related to
      aggressiveness of Pythium aphanidermatum on tomato at high soil temperature (>30
      degrees C). Several methods such as using biological control agents, fungicides
      and other cultural practices were applied in attempts to control tomato sudden
      death. Three Trichoderma harzianum and two Trichoderma virens isolates were
      evaluated for biocontrol of the disease in the greenhouse and in the field T.
      harzianum and T. virens isolates were separately used to treat the seed, potting
      medium and also incorporated into the soil before transplanting. Field soil was
      naturally infested with P. aphanidermatum, while greenhouse soil was inoculated
      with the pathogen 10 days after transplanting. All treatments were flooded for 48
      hrs at 32 degrees C soil temperature. Results from this study show that most
      tested T. harzianum and T. virens isolates have little promise for control of
      tomato sudden death following flooding. The percentage of tomato plants that
      wilted after growing in soil treated with either T. harzianum or T. virens and P.
      aphanidermatum was not significantly different when compared to the soil treated
      with P. aphanidermatum alone. No wilted plants were observed in the control (non
      treated soil).

PMID- 15151281
TI  - Establishment of a Trichoderma atroviride strain in some organic products.

PMID- 15151282
TI  - Innovative combination of IPM (integrated pest management) tools--the IPM sugar
      beet model.

PMID- 15151280
TI  - Efficacy of salts against fungal diseases in glasshouse crops.
AB  - The constant input of chemical fungicides against foliar diseases in glasshouse
      crops has instigated research on alternative control substances. Various salts
      have been mentioned in the literature and we have tested several bicarbonates,
      sulphates and phosphates against powdery mildew fungi in cucumber, tomato, sweet
      pepper and rose and against Bremia lactucae in lettuce. The experiments were run
      according to EPPO guidelines for efficacy in glasshouses of Applied Plant
      Research (PPO). Plants were sprayed weekly and disease and yield were assessed.
      In cucumber, NaHCO3, KHCO3, MgSO4 and MnSO4 all reduced powdery mildew
      significantly, with MnSO4 as the most effective agent. In tomato, MgSO4, MnSO4
      and KH2PO4 all reduced powdery mildew by approx. 40% whereas NaHCO3 and KHCO3
      gave approx. 95% control. In pepper, NaHCO3 controlled Leveillula taurica by 50
      90% compared to the untreated control. In rose, the efficacy of KH2PO4, MnSO4,
      MgSO4, NaHCO3 and KHCO3 against powdery mildew differed between cultivars. In
      general, the bicarbonates were the most effective compounds. In lettuce, NaHCO3
      reduced Bremia severity by 70 to 80%. The conclusion of this range of experiments
      is that especially bicarbonates can be a good alternative for control of foliar
      fungal diseases in glasshouse crops. The effective concentration is not causing
      any symptoms of phytotoxicity, provided that spraying is not done at high
      irradiation conditions. Bicarbonates have been submitted for the Dutch list of
      exceptions on the Pesticide Law.

PMID- 15151283
TI  - The IPM Wheat Model--results of a three-year study in North Rhine-Westphalia,
      Lower Saxony and Schleswig-Holstein.
AB  - Under the primary utilisation of phytosanitary production factors such as
      selection of variety, crop rotation and N fertilisation according to plant
      requirements, the IPM Wheat Model comprises the elements diagnosis (qualitative =
      type of pathogen, quantitative = disease severity), scientifically grounded
      treatment thresholds which, as critical values in pathogen development, can be
      applied to define the optimum time of fungicide application, and pathogen
      specific effective fungicides and application amounts. This leads to the location
      and year-specific optimised control of the pathogen and of the associated yield
      performance. After several years of development in Bavaria (from 1985 on) and
      Schleswig-Holstein (1993-1999), the model was tested as part of a project
      involving the Universities of Bonn and Kiel and the plant protection services of
      the German states of Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein
      in a three-year study (1999-2001) in interregional locations (usually nine per
      state) with the winter wheat variety Ritmo (interregional indicator variety) and
      a further variety of regional importance in different variations (untreated
      control, three to four times growth stage-oriented variants for the determination
      of the absolute damage potential, IPM-variant). In exact records (approx. 12
      dates per vegetation period), the disease epidemics were recorded weekly. With
      the genetically uniform indicator variety Ritmo, the results documented
      substantially differing year- and location-specific disease and yield patterns.
      Interregionally, a broad wheat pathogen spectrum (Puccinia striiformis, P.
      recondita, Septoria tritici, Stagonospora (syn. Septoria) nodorum, Blumeria (syn.
      Erysiphe) graminis, Pseudocercosporella herpotrichoides, Drechslera tritici
      repentis) in differing composition, disease severity and damage effect was
      demonstrated. The heterogeneity of the infection and damage patterns was
      increased in the case of the second variety, in association with the genetic
      variability. The epidemiologically-orientated indications (average two, reduced
      application amounts) according to the IPM Wheat Model in association with time
      diverging progressions led, on an interregional basis, with minimum input and in
      association with the diverging dynamics, to a biologically and economically
      optimised fungicide application. In the context of economic and ecological
      performance, the comprehensive results of the project demonstrated the valuable
      functionality of the IPM Wheat Model.

PMID- 15151284
TI  - Efficacy of different fungicides against Rhizoctonia brown patch and Pythium
      blight on turfgrass in Italy.
AB  - Brown patch, incited by Rhizoctonia solani Kuhn, and Pythium blight, caused by
      Pythium spp. are two of the diseases most frequently observed on turfgrass in
      high maintenance stands, as on golf courses. In such conditions the control
      strategies, based on chemicals, are particularly difficult due to the scarcity of
      fungicides registered for turf in Italy. The results obtained in experimental
      trials carried out to evaluate the efficacy of chemical and biological products
      against brown patch and Pythium blight are reported. On mature turfgrass,
      maintained under fairway conditions, azoxystrobin, and trifoxystrobin, not yet
      registered on turf, were very effective against brown patch. Tebuconazole,
      applied in three different formulations, was very effective against R. solani,
      while Trichoderma spp. and azadiractine did not control the pathogen. In
      greenhouse conditions on Agrostis stolonifera, in the presence of severe disease
      incidence, due to artificial inoculation, benalaxyl-M satisfactorily controlled
      Pythium blight; Trichoderma spp. as well as a commercial formulation of T.
      harzianum, applied one week before the inoculation, were not effective. Among the
      fungicides not yet registered for use on turfgrass in Italy, metalaxyl-M +
      mancozeb was effective against Pythium blight.

PMID- 15151286
TI  - Identification of fungal diseases associated with imported wheat in Iranian
      silos.
AB  - In this study, imported wheat varieties used for cookies and bread making were
      evaluated for the presence of fungal diseases in the silos. Grain samples were
      taken and cultured on nutrient agar medium and sterile papers impregnated with
      nutrient. The results showed the presence of pathogenic fungi such as Ulocladium
      sp., Cladosporium sp., Alternaria sp., Rhizopus nigricans, Penicillium sp. and
      Trichothecium sp. in varieties from Australian, Mucor sp., R. nigricans, Fusarium
      sp., A. triticum, Helminthosporium sp. and Penicillium sp. from Argentina,
      Alternaria sp., Ulocladium sp., Penicillium sp., Aspergillus sp., Mucor mucedo,
      R. nigricans, Fusorium sp., Curvularia triticola, U. clamydosporium and C.
      tritici from Kazakistan varieties stored in Karaj silos or unloading trains. It
      is noteworthy to mention that Fusarium sp., Helminthosporium sp., Alternaria sp.,
      A. tritici, A. triticola and U. clamydosporium are phytopathogenic fungi that
      often cause serious diseases on crops, produce lots of spores that are widely
      disseminated across the field and grow and reproduce in plant residues and
      diseased or wounded plant tissues and mature grains particularly under moist
      conditions. If in case, farmers try to use contaminated wheat grains that are
      distributed among them for flour, for cultivation purposes, it is highly probable
      that new fungal strains and species will be introduced in the areas where wheat
      production has never been threatened before. Fungal disease such as Indian smut
      or rusts is not native to Iran but are considered quarantine diseases. In
      addition, high incidence of contamination due to the presence of mycotoxins
      produced by Penicillium sp. and Aspergillus sp. in foreign wheat cultivars, could
      result in serious toxicity and illness in humans and birds.

PMID- 15151285
TI  - First detection of resistance to QoI fungicides in Mycosphaerella graminicola on
      winter wheat in Belgium.
AB  - A total of 740 Mycosphaerella graminicola strains were isolated between 2000 and
      2002 from winter wheat F1 or F2 leaves showing Septoria leaf blotch lesions (SLB)
      collected mainly at the soft dough stage in fungicide trials, analysing at 12
      locations in Belgium the possibilities and risks associated with the use of
      epoxiconazole and azoxystrobin at various doses, mixtures and application dates.
      Fungicide sensitivity tests were performed in microtitre plates on potato
      dextrose broth amended with various concentrations of azoxystrobin. A wide range
      of sensitivity to azoxystrobin was observed, with EC50 values ranging for 735
      strains between 0.002 to 0.7 microg/ml, the highest frequency gradually shifting
      from EC50 classes 0.01 and 0.02 microg/ml azoxystrobin in 2000 to EC50 classes
      0.02 and 0.04 microg/ml in 2002. No clear selection effect of particular
      fungicide use strategies was observed. Among the 382 strains isolated in 2002,
      five originating from 2 locations, showed azoxystrobin EC50 values >1 microg/ml.
      On medium amended with 100 microg/ml salicylhydroxamic acid (SHAM), 58% of the
      2002 strains were strongly inhibited, which affected adequate azoxystrobin ED50
      determination. This suggests widespread occurrence of M. graminicola strains
      relying in vitro on the alternative respiration pathway. In the presence of SHAM,
      strains 339 and 880 showed azoxystrobin EC50 values of 3 and >30 microg/ml,
      respectively. This high level of resistance to a QoI fungicide was confirmed by
      analysing mycelium growth inhibition on PDA. Cross-resistance to trifloxystrobin
      and kresoxim-methyl was demonstrated. Greenhouse assays on wheat plants revealed
      that control of QoI resistant strains by azoxystrobin is decreased, compared to
      control of sensitive ones. This highlights the risk of resistance to QoI
      fungicides also in M. graminicola populations, although up to now no decrease in
      field performance was noticed. It is recommended to delay build up of QoI
      resistance by an integrated approach, combining optimised fungicide use with the
      choice of SLB resistant cultivars and the application of farming practices
      promoting stubbles break down and so the reduction of the teleomorph stage.

PMID- 15151288
TI  - Biological control of Fusarium oxysporum, the causal agent of onion wilt by
      antagonistic bacteria.
AB  - Fusarium wilt caused by Fusarium oxysporum Sch. is one of the most important
      diseases of onion in Iran. Application of chemicals especially as soil drench,
      increased cost of onion production and may be dangerous for environment. One of
      the effective techniques to suppress soil-born diseases in biological control
      with antagonistic rhizobacteria. Experiment were carried out with 120 bacterial
      isolates that were collected from onion rhizosphere. Six highly effective
      isolates were selected from these antagonists for subsequent studies. These
      strains were used to investigate their biocontrol traits in vitro and their
      ability to suppress the onion wilt in vivo (soil and seed treatments). According
      to the biochemical, physiological and morphological test, the isolates 22, 38, 46
      and 52 were identified as Bacillus spp. The isolates 16 and 48 were identified as
      Pseudomonas fluorescens. The isolates of Bacillus spp. produced volatile
      metabolites that inhibited mycelia growth of Fusarium oxysporum. In soil
      treatment, the isolates 22 and 52 with 56% and 51% had the highest effect in
      reducing the Fusarium wilt of onion. The mixture of two isolates reduced 60% the
      disease. In seed treatment the isolate 22 with 41% had the greatest effect on
      reducing the onion Fusarium wilt.

PMID- 15151287
TI  - Cloning and expression of pinB gene from Triticum monococum seeds.
AB  - Puroindolines (PIN) are low molecular weight, cysteine-rich, endosperm-specific,
      basic proteins with a unique tryptophan-rich domain found in wheat (Triticum
      aestivum L.) and barley (Hordeum vulgare L.) as well as other members of
      Triticaceae. PINs appear to be involved in both flour softness as well as
      resistance against fungal diseases. These proteins are known to be the major
      components of 'friabilin' associated with the surface of water washed starch
      grains and possess lipid binding properties. Structural characterization of
      puroindolines from Triticum monococum was initiated by amplifying and
      subsequently cloning the corresponding pin gene into an expression vector, known
      as pET-32a(+). The protein contains five tryptophanin domains and ten cysteine
      residues. The pinB gene was fused with the 109aa Trx.Tag thioredoxin for a high
      level expression. The cloning sites used for producing fusion proteins also
      contained cleavable His.Tag and S.tag sequences for detection and purification.
      After transformation of competent Origami cells, fusion protein expression was
      detected by growing a transformant in LB medium in the presence of 0.1 mM IPTG at
      room temperature for 6 hrs on a shaker. Both soluble and insoluble fusion
      proteins were extracted from Origami cells after sonication. Ni-NTA column
      (Qiagen) was used to extract and purify these fractions. Following an overnight
      digestion of the recombinant protein with enterokinase at room temperature, the
      corresponding fractions were electrophoresed in polyacrylamide gel,
      electroblotted onto a nitrocellulose membrane and cross-reacted with the anti
      friabilin monoclonal antibody. We found that the recombinant PINB protein had a
      molecular weight of 16 kDa whereas TrxB was 21 kDa. Fusion protein ran at 34 kDa.
      PINB protein from wheat was shown to be immunologically related to a homologue,
      tryptophanin, in oat seed. Further study is currently underway to characterize
      these proteins structurally using NMR.

PMID- 15151289
TI  - Identification of physiological races of Blumeria graminis f. sp. tritici and
      evaluation of powdery mildew resistance in wheat cultivars in Sistan province,
      Iran.
AB  - Powdery mildew of wheat caused by Blumeria graminis f. sp. tritici (Bgt) is one
      of the most important fungal diseases in Iran. During the years 1998-2001, wheat
      fields in Sistan province were surveyed and powdery mildew infected samples were
      collected from various areas and transferred to the laboratory. In the
      greenhouse, fungal spores were purified and inoculated onto susceptible wheat
      cultivars using single pustule and single spore procedures. Selected pure
      isolates were inoculated onto the first leaves of eight differential wheat
      varieties for identifying physiological races. The results showed the existence
      of Bgt races 5, 11, 14, 19, 21, 24, 27, 28, 31, 32, 44, 50, 53, 58, 66, 73 and 84
      in Sistan. These races were new to Sistan province and Iran as a whole. Among 17
      races studied, races 11, 53 and 73 were important dominant races thus
      constituting 40% of total population. Race 53 constituted 16% of all isolates and
      was the dominant race in the area with 62.5% pathogenicity. Therefore, this race
      was introduced as the most virulent race during the period of this study. This
      study showed that Bgt isolates were compatible with host plant genes pm8, pm3 and
      pm3b but incompatible with gene pm4b. Powdery mildew resistance was evaluated
      using race 11 on 70 wheat cultivars during seedling stage as well as adult plant
      under both greenhouse and field conditions between 1999 and 2001. Among wheat
      lines tested for resistance against powdery mildew, cultivar Hirmand resembled
      the differential line Weihenst M1 in that both may possess gene pm4b and showed
      no symptoms under the greenhouse and field conditions. Cultivar Chamran was found
      to be highly resistant whereas Sorkhtokhm was susceptible. Other cutivars showed
      partial and gradual resistance against the powdery mildew disease.

PMID- 15151290
TI  - Susceptibility of Capsicum breeding lines to NTN strain of Potato virus Y
      (PVY(NTN)) and Obuda pepper virus (ObPV).
AB  - The objective of this study was to examine the reaction of 12 Capsicum breeding
      lines to NTN strain of Potato virus Y (PVY(NTN)) and 16 lines to Obuda pepper
      virus (ObPV). Inoculated plants were symptomatologically and serologically
      checked for virus infection. Back inoculation was also carried out to Nicotiana
      tabacum 'Xanthi-nc' and N. tabacum 'Samsun' as indicator plants. Out of the 12
      lines tested four (32.Bogyiszloi, 4/99 F2, 17/99 F2 and VI-61 in.) proved to be
      resistant (immune) to PVY(NTN). Seven Capsicum lines (9/99 F2, 17/99 F2, V-21 =
      28/98 F3, V-28 = 36/98 F3, V-3 = 7/98 F2, V-6 = 13/98 F2, and V-10 = 17/98 F2)
      showed hypersensitive reaction to ObPV. Other breeding lines were susceptible to
      ObPV infection. One line (17/99 F2) showed immunity to PVY(NTN) and
      hypersensitivity to ObPV at the same time, therefore this one is considerably
      valuable for breeding pepper varieties for multivirus resistance.

PMID- 15151291
TI  - Reaction of Lycopersicon species and varieties to Potato virus Y (PVY(NTN)) and
      Tomato mosaic virus (ToMV).
AB  - Virus susceptibility of 33 Lycopersicon species and varieties to NTN strain of
      Potato virus Y (PVY(NTN)) and Tomato mosaic virus (ToMV) were studied. Inoculated
      plants were tested for infection symptomatologically, serologically and by back
      inoculation as well. New incompatible and compatible host-virus relations have
      been determined. All tested plants were susceptible to ToMV. However,
      Lycopersicon esculentum Mill. convar. parviboccatum Lehm. var. cerasiforme (Dun.)
      Alef. s.l., L. peruvianum (L.) Mill. and L. hirsutum Humb. et Bonpl. were extreme
      resistant (immune) to PVY(NTN). Other species were susceptible. Resistant
      lycopersicon genotypes could be used as sources for virus resistance.

PMID- 15151292
TI  - Rapid detection and identification of tomato vascular wilt pathogens using a DNA
      array.
AB  - Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici, and Verticillium
      wilt, caused by either Verticillium albo-atrum or V. dahliae, are devastating
      diseases of tomato (Lycopersicon esculentum Mill.) found worldwide. Monitoring is
      the cornerstone of integrated pest management of any disease. The lack of rapid,
      accurate, and reliable means by which plant pathogens can be detected and
      identified is one of the main limitations in integrated disease management. In
      this paper, we describe the development of a molecular detection system, based on
      DNA array technology, for rapid and efficient detection of these vascular wilt
      pathogens. We demonstrate that by using this array these pathogens can be
      detected within 24 h from complex substrates like soil, plant material, and
      samples as they are collected by tomato growers in their greenhouses.

PMID- 15151293
TI  - An ultrastructural investigation of the 'microsclerotia' formed in single cells
      of root cortical cells associated with corky root rot of tomato.
AB  - White and Scott (1973) described two forms of microsclerotia associated with
      corky root rot of tomato, one being formed in single cells of the outer root
      cortical cells and the other produced in culture from isolation of diseased roots
      and in degenerated root debris. By assuming that both forms were of fungal
      origin, they conducted an ultrastructural study using the microsclerotia produced
      in culture but not those formed in single cells. They demonstrated that the
      microsclerotia from culture consisted of hardened, interwoven hyphae of the
      fungus, Pyrenochaeta lycopersici. Since there have been doubts about the nature
      of the microsclerotia formed in single cells, an ultrastructural study was
      conducted. The results demonstrated clearly that the 'microsclerotia' formed in
      single cells of the root cortical cells were not composed of fungal mycelia,
      indeed these blackened cells or 'microsclerotia' were filled with numerous
      crystallines. There was no evidence of the presence of fungal hyphae in or around
      these cells. Both diseased and healthy, and young and old root cortex cells of
      many cultivars of tomato contained cells filled with crystallines. Therefore, it
      is clear that the 'microsclerotia' formed in single cells of the outer cortex
      described by White and Scott are not microsclerotia of the fungus, P.
      lycopersici.

PMID- 15151295
TI  - Pathogenicity of Phytophthora infestans on solanaceous and asteraceous plant
      species in Cameroon.
AB  - Experiments were conducted to detect potential hosts of Phytophthora infestans,
      causal agent of potato late blight. Isolates of P. infestans recovered from
      garden huckleberry (Solanum scabrum), potato (S. tuberosum) and tomato
      (Lycopersicon esculentum) were inoculated on detached leaves of 12 solanaceous
      and 14 asteraceous plant species collected in and around potato fields in the
      western highlands of Cameroon. The inoculated leaves were maintained in Petri
      dishes in the laboratory for 7 days at 20-22 degrees C. Isolates of P. infestans
      from huckleberry, potato and tomato infected the same host plants as well as the
      gboma eggplant (Solanum macrocarpon) and two asteraceous weeds, Ageratum
      conyzoides and Solanecio biafrae. Inocula recovered from infected S. macrocarpon
      caused late blight symptoms on huckleberry, potato and tomato both under
      laboratory and screen house conditions, while those from both asteraceous weeds
      reinfected potato in the laboratory and inoculum from S. biafrae reinfected
      huckleberry in the screen house. This is a first observation of late blight
      infection on S. macrocarpon, A. conyzoides and S. biafrae in Cameroon. Results
      indicate the importance of both asteraceous weeds and S. macrocarpon as potential
      alternative hosts for P. infestans in garden huckleberry, potato or tomato
      fields.

PMID- 15151294
TI  - Phytopthora ramorum in Belgium: 2002 survey results and research efforts.
AB  - Phytophthora ramorum is a new and aggressive Phytophthora species that causes
      leaf blight and dieback symptoms on Viburnum and Rhododendron plants in Europe. A
      variant of this fungus is responsible for Sudden Oak Death (SOD) in California
      and Oregon. In Europe, problems so far are mostly restricted to nursery plants of
      Rhododendron and Viburnum while in the US, the fungus has been isolated from over
      20 host species and is responsible for massive killing of oak trees (mostly
      Quercus agrifolia and Lithocarpus densiflorus) in forest and park settings. The
      potential for infection of native tree species in Europe and the recent detection
      of the fungus in nurseries of several European countries has lead to the
      implementation of EU emergency phytosanitary measures. As a result, most European
      countries have conducted surveys and are doing research as part of risk
      assessment efforts. The first part of this paper focuses on the plant diagnoses
      of the 2002 survey of P. ramorum in Belgian nurseries. The data from the survey
      indicates P. ramorum is present in Belgium at similar rates as in the
      neighbouring countries, in an apparent random distribution. The second part of
      this paper describes research results relating to the in vitro effect of oomycete
      fungicides on P. ramorum, Rhododendron cultivar susceptibility, the determination
      of the leaf infection site, and pathogen survival. Some fungicides had excellent
      in vitro activity against P. ramorum and should be tested further on plants. Use
      of host resistance as a control strategy may be limited as little difference in
      cultivar sensitivity was observed. Infection studies showed that wounds and the
      lower sides of the leaves are most susceptible to infection. Once the pathogen
      gets inside, it can survive well on detached leaves, especially when they are
      kept cool and moist. These data can contribute to management decisions of P.
      ramorum at the level of nurseries as well as the government.

PMID- 15151296
TI  - Effect of soil moisture on seed germination, plant growth and root rot severity
      of navy bean in Fusarium solani infested soil.
AB  - The development of root rot and its severity were affected by numerous factors
      which through their interaction could distort results. In this study, a single
      factor, soil moisture was considered. Using Fusarium solani infested root rot
      soil we investigated the effect of three available soil moisture (ASM) levels
      (i.e. 100%, 70% and 25%) on seed rot, germination, plant growth and root rot
      severity of navy bean in the greenhouse. Percent germination differed strikingly
      averaging of 58.5, 89.5 and 87.0% respectively to ASM levels. Apparently, high
      soil moisture promoted seed rot and impeded seed germination. Root rot incidence
      and severity were examined two months later. Percent plant with root rot averaged
      89.5, 89.0 and 69.8% while root rot severity was 3.01, 2.3 and 1.1 (on a 0-9
      scale), respectively to ASM levels. Plant growth was moderate, good and poor with
      respect to ASM levels. It was apparent that the final plant growth was a sum of
      seed rot, root rot incidence, disease severity and soil moisture adequacy.
      However, seed rot appeared to be the largest contributing factor to final plant
      yield.

PMID- 15151297
TI  - Hydroponic chrysanthemum production: cultural and pathological issues.
AB  - Hydroponic culture has not replaced soil culture in greenhouse production of
      chrysanthemum (commonly known as 'mum'). This study examines cultural or
      pathological conditions that might have affected the conversion from soil to
      hydroponic production. Cultural factors investigated included hydroponic
      container size and shape and oxygenation of the nutrient solution. Disorders
      encountered during the studies included salt wicking during rooting of the
      cuttings and severe Pythium infection in the third and successive crops in a
      hydroponic system. Mums did not appear to respond to various shapes and sizes of
      containers and troughs in which they were grown. Also, increased oxygenation had
      little effect on pythium root rot and plant growth. Rooting of cuttings in a
      polyethylene covered hydroponic system reduced wilting, whereas salt wicking was
      severe without a plastic covering. Pythium disease was severe in the third and
      successive crops in the same hydroponic system. The disease could be overcome by
      raising the cuttings in a peat-based growing medium in perforated plastic cells
      and then transplanting the seedlings along with the peat moss cubes into a
      hydroponic system.

PMID- 15151298
TI  - New and remarkable records of microfungi from Turkey.
AB  - During a botanical excursion of the University of Essen in the year 2002 to North
      , Central- and South-Anatolia we have collected representatives of about 100
      genera of microfungi as parasites or saprophytes on crops and wild plants. Some
      of them are new for Turkey: Passalora dubia on Atriplex hortensis,
      Pseudocercospora ligustri on Ligustrum ovalifolium, Passalora smilacis on Smilax
      aspera, Uromyces limonii on Limonium spec., Puccinia jasmini on Jasminim spec.,
      Sawadea bicornis on Acer negundo, Puccinia sii-falcariae on Falcaria vulgaris,
      Phomia hedericola on Hedera helix, Camorosporium pistaciae on Pistacia
      terebinthus, Erysiphe bahrii on Silene spec., Ramularia heraclei on Apium
      graveolens. All specimens are located in the Herbarium ESS, Mycotheca parva,
      collection G.B. Feige & N. Ale-Agha.

PMID- 15151299
TI  - Second report of microfungi in eastern Westphalia (Sauerland, Northrhine
      Westphalia, Germany).
AB  - 39 microfungi from 25 different genera, including Ascomycetes of the orders
      Erysiphales, Meliolales, Helotiales and Pseudosphaeriineae and Basidiomycetes of
      the orders Uredinales as well as Hyphomycetes and Coelomycetes were found. The
      examined samples have been collected in Germany, Northrhine-Westfalia, in the
      area named Sauerland in the period of March 2000 to June 2002. Cytonema spinellum
      (Kalchbr.) Hohn, and Melanospora caprina (Fr. ex Hornem.) Sacc. as a hypoparasit
      are recorded for Germany for the first time. The samples are deposited in the
      Herbarium Essen (Mycotheca parva Slg. Feige/Ale-Agha).

PMID- 15151300
TI  - New, rare and remarkable microfungi from Macedonia (Greece).
AB  - On the occasion of the great excursion of the Botanical Institute of the
      University of Essen in the year 2000 we were able to collect about 250 species of
      parasitic and saprophytic microfungi in eastern Greece. Dominant were
      Ascomycetes, Basidiomycetes and Deuteromycetes, for example Puccinia convolvuli
      on Calystegia silvatica, Puccinia caricina on Carex flava, Ramularia cynoglossi
      on Cynoglossum creticum, Phyllosticta juglandis and Marssonina juglandis on
      Juglans regia, Erysiphe cynoglossi on Echium italicum and Hendersonia culmiseda
      on Phragmites australis. Many of our collections contain rare and to a great
      extend unknown species for the area of investigation. All samples are located in
      the Herbarium ESS, Mycotheca parva, collection G.B. Feige & N. Ale-Agha.

PMID- 15151301
TI  - Field response of some asparagus varieties to rust, Fusarium crown root rot, and
      violet root rot.
AB  - Research was carried out to evaluate the behaviour of some asparagus genotypes
      against three most important fungal diseases: 1) asparagus rust caused by
      Puccinia asparagi D.C.; 2) Fusarium crown and root rot caused by Fusarium
      oxysporum (Schlecht.) f.sp. asparagi (Cohen & Heald) and Fusarium proliferatum
      (Matstush.) Nirenberg; 3) violet root rot caused by Rhizoctonia violacea Tul. The
      object of this research was also to found an eventual correlation between the
      plant susceptibility to asparagus rust and the sensibility to Fusarium crown root
      rot and violet root rot attacks. Resistant genotypes to rust should be less
      susceptible to attacks from F. oxysporum f.sp. asparagi, F. proliferatum and R.
      violacea, a fungal complex causing the plant decline. Asparagus genotypes were
      compared in a randomized complete block experiment design, replicated four times,
      in order to search that ones showing the best behaviour to escape the diseases.
      Phytopathological observations were carried out on November when the control
      plots showed 100% infected plants. The pathogens were isolated and identified.
      The diseased plants were registered. According to symptom evaluation scales, all
      the plants were grouped into infection classes, calculating frequency and
      McKinney index. Wishing to learn something about the infection trend of F.
      oxysporum f.sp. asparagi or R. violacea in relation to P. asparagi attack, the
      relative curvilinear regressions were calculated. The Italian cultivars "Marte"
      and "Grande" showed significantly the best behaviour in terms of resistance to
      asparagus rust, exhibiting 37% and 42% of diseased plants. The McKinney index was
      9.1% and 15.6%, respectively. The susceptible plots showed 100% of infected
      plants and different McKinney index: 46% for "Eros", about 60% for "H 519",
      "Atlas" and "Golia", over 70% for the remainder. "Marte" and "Grande" showed good
      tolerance to F. oxysporum f.sp. asparagi and to R. violacea exhibiting up to 100%
      of healthy plants. The regression between plants affected by asparagus rust and
      those diseased by Fusarium crown root rot showed a linear equation with a
      regression coefficient b = 1.186 and a correlation coefficient R2 = 0.98. The
      regression between infection caused by rust and that caused by violet root rot
      exhibited a regression coefficient b = 1.03 and a coefficient of correlation R2 =
      0.9. "Marte" and "Grande" exhibited the best behaviour against the rust attacks.
      Plants without rust were tolerant to pathogens causing plant decline.

PMID- 15151302
TI  - Fungal diseases on winter wheat in transdanubian region.
AB  - Dominancy proportions of some wheat-pathogenic fungi were investigated by the
      authors in Hungary, near to the lake Balaton, in the years 2001-2002. In small
      plot trials, each 10 species of fungi from two breeding institutes were surveyed.
      In the year 2001, the dominant pathogen was Puccinia recondita f. sp. tritici.
      During the breeding season the infectedness increased gradually and reached up to
      28.50% by middle of May. The infectedness of some species came near to 50-90% by
      this time. In the year 2002, the brown-rust infectedness was of smaller measure
      than a year before. The infectedness caused by Puccinia stiiformis was
      considerable only in 2001 although it did not reach the level of the leaf-rust.
      The measure of the infectedness caused by Blumeria graminis f. sp. graminis
      proved to be considerable in not one of the years investigated. The flag-leaves
      and ears of several species were damaged seriously in 2001 while the powdery
      mildew infectedness of wheat remained small in 2002. The damages of small measure
      are mainly caused by the extremely dry weather.

PMID- 15151303
TI  - Sheath rot of rice in Iran.
AB  - Sheath rot of rice occurs in most rice-growing regions of the world. It usually
      causes yield losses from 20 to 85%. Sheath rot was reported from Iran in 1993.
      Year after year, the number of diseased plants increased in the Northern Iran. In
      summer of 2001, these symptoms were observed in most fields: lesions occur on the
      upper leaf sheaths, especially the flag leaf sheath. As the disease progresses,
      lesions enlarge and coalesce and may cover most of the leaf sheath. Panicle may
      fail to completely or at all. Brown or partially brown not filled or partially
      filled grain is also associated with infection of the panicle. A whitish powdery
      growth may be found inside affected sheaths. Infected plants were collected and
      trasferred to laboratory. Small pieces of diseased tissues were washed under tap
      water for one hour. Then tissues were placed on WA and incubated at 25 degrees C.
      These isolates were purified and identified as: Sarocladium oryzae, Fusarium
      udum, F. semitectum, F. avenaceum, F. flocciferum, F. graminearum, Bipolaris
      oryzae, Alternaria padwickii, Rhizoctonia solani, Paecilomyces sp., Nigrospora
      sp. and Trichoderma sp. This is the first report of F. udum in Iran. Also this is
      the first report that rice is the host for F. semitectum, F. avenaceum and F.
      flocciferum in Iran. Pathogenicity tests were conducted in glass house. Following
      species were found to be associated with sheath rot of rice: S. oryzae, F.
      graminearum, F. udum, F. avenaceum, B. oryzae, A. padwickii. This is the first
      report in the world that F. udum and A. padwickii are the causal agents of the
      sheath rot on rice plants.

PMID- 15151305
TI  - Identification and characterization of pathogenic fungi causing spot disease on
      rhubarb (Rheum raponticum L.) in the UK.
AB  - This study reports on the acquisition of significant susceptibility of clonal
      rhubarb, produced by micropropagation, to leaf and petiole spot disease when
      compared to conventionally propagated material. This alteration in response to
      pathogens accompanies previously reported reductions in growth rate and poor
      winter survival. The two fungi isolated from lesions of both leaves and petioles
      have been identified as Ascochyta rhei and Romularia rhei, the former not
      previously having been reported in this role. Both fungi are able to cause spot
      infection of leaves and petioles of the micropropagated material. The effect of
      temperature on leaf infection from both fungi showed an optimum near 25 degrees C
      for A. rhei and close to 20 degrees C for R. rhei.

PMID- 15151304
TI  - Development of a selective medium for the determination of the spore
      concentrations of Botrytis cinerea in the air.
AB  - Gray mold, caused by Botrytis cinerea, is an important disease that causes world
      wide extensive damage to a wide range of economically important crops. When it is
      necessary to determine the spore concentration of Botrytis cinerea in a certain
      area, it is important to develop a method that can capture the spores of Botrytis
      cinerea and that can identify them. For the identification and enumeration of the
      plant pathogen Botrytis cinerea in the environment the easiest method available
      for the moment is the use of a selective medium. Several selective media for the
      isolation of Botrytis spp. have been developed by other research groups. All
      these media contain fungicides that are usually non-toxic towards Botrytis
      species and tannic acid, which is oxidized to produce a brown pigment that
      visualises the growth of Botrytis cinerea on the selective media. It seemed that
      different isolates of Botrytis cinerea that are found in nature have different
      sensitivities towards the different fungicide concentrations that are used in the
      selective media. Making the "optimal" selective media for Botrytis cinerea, we
      have to take in consideration that so many as possible Botrytis cinerea isolates
      must be able to germinate and grow on this selective medium and that the
      contamination of other micro-organisms on the selective medium must be minimized.
      Before the final composition of our selective medium for Botrytis cinerea,
      different combinations of fungicide concentrations were tried out of the
      following three fungicides: Rubigan, maneb and PCNB (pentachloronitrobenzene).
      All these selective media with different fungicides concentrations were tested
      out for spore germination and mycelium growth of Botrytis cinerea. Because it was
      obvious that the percentage Botrytis cinerea that germinated on PDA (Potato
      Dextrose Agar) was higher than on the selective medium a few experiments were
      executed in which the percentage of spore germination on PDA was compared with
      the percentage of spore germination on selective media. From the results of these
      experiments a correction factor was calculated that will be used when spore
      concentrations have to be determined for air detections that are carried out in
      glasshouses.

PMID- 15151306
TI  - Alder phytophthora in Poland: occurrence and plants colonization.
AB  - Common alder (Alnus glutinosa) decline has been observed in Poland during the
      last 6 years. Alder Phytophthora was recorded, however, only from one sampling
      area in the middle of the country. Species of Armillaria, Fusarium, Mucor,
      Penicillium and Trichoderma were also isolated from diseased trees. Inoculation
      of alder stem parts, leaves and seedlings with Phytophthora isolates resulted in
      the development and spread of necrosis. Studies will be continued in the nearest
      years.

PMID- 15151307
TI  - Activity of some chemicals in the control of Botrytis cinerea on roses.
AB  - In the control of grey mould (Botrytis cinerea) on rose petals all 15 tested
      fungicides used as a spray, suppressed very effectively development of necrosis.
      But the best results in suppression of necrosis development, more than 90%
      effectiveness gave: Amistar 250 SC (azoxystrobin), Bravo 500 SC (chlorothalonil),
      Discus 500 WG (kresoxim methyl), Euparen 50 WP (dichlofluanid) Euparen Multi 50
      WG (tolyfluanid), Folpan 80 WG (folpet), Kaptan zaw. 50 WP (captan), Penncozeb 80
      WP (mancozeb), Ronilan 50 WP (vinclozolin), Rovral Flo 255 SC (iprudione),
      Sumilex 500 SC (procymidone) and Teldor 500 SC (fenhexamid). When Dithane M-45 80
      WP (mancozeb), Sarbrawit 530 SC (chlorothalonil + carbendazim) or Topsin M 70 WP
      (thiophanate methyl) were used, the diameter of spots was about 6-times smaller
      than on control flowers (about 84% effectiveness). All tested fungicides used for
      spraying of flower petals with abundant visible sporulation of B. cinerea were
      ineffective in the inhibition of spore germination. But when Petri dishes with
      potato-dextrose-agar were sprayed with tested fungicides and inoculated with
      spore suspension, Euparen 50 WP, Euparen Multi 50 WG, Folpan 80 WG, Kaptan zaw.
      50 WP and Penncozeb 80 WP completely suppressed conidia germination.

PMID- 15151308
TI  - Minor uses: national and international activities.
AB  - Through the national and international approaches we hope to achieve proper
      solutions for minor use problems. At the national level, the following
      foundations/parties give support to organizations/individuals who need support in
      finding solutions: [table: see text] At the international level the Minor Use
      Helpdesk, but especially the Technical Group within the Expert Group on Minor
      Uses initiated by the EU Commission, will play an important role in solving minor
      use problems.

PMID- 15151309
TI  - Benchmarking farmer performance as an incentive for sustainable farming:
      environmental impacts of pesticides.
AB  - Pesticide use in The Netherlands is very high, and pesticides are found across
      all environmental compartments. Among individual farmers, though, there is wide
      variation in both pesticide use and the potential environmental impact of that
      use, providing policy leverage for environmental protection. This paper reports
      on a benchmarking tool with which farmers can compare their environmental and
      economic performance with that of other farmers, thereby serving as an incentive
      for them to adopt more sustainable methods of food production methods. The tool
      is also designed to provide farmers with a more detailed picture of the
      environmental impacts of their methods of pest management. It is interactive and
      available on the internet: www.agriwijzer.nl. The present version has been
      developed specifically for arable farmers, but it is to be extended to encompass
      other agricultural sectors, in particular horticulture (bulb flowers, stem
      fruits), as well as various other aspects of sustainability (nutrient inputs, 'on
      farm' biodiversity, etc.). The benchmarking methodology was tested on a pilot
      group of 20 arable farmers, whose general response was positive. They proved to
      be more interested in comparative performance in terms of economic rather than
      environmental indicators. In their judgment the benchmarking tool can serve a
      useful purpose in steering them towards more sustainable forms of agricultural
      production. The benchmarking results can also be used by other actors in the
      agroproduction chain, such as food retailers and the food industry.

PMID- 15151310
TI  - The heterogeneity of sprout inhibitor application with chlorpropham.
AB  - The CIPC or chlorpropham is used on potatoes as "sprouting inhibitor". These
      lasts years, some set of belgian potatoes treated by CIPC exceeded the Maximum
      Residue Limit (MRL), fixed at 5 mg/kg. The heterogeneity of sprout inhibitor
      application would be one of the causes of over-dosage. In order to estimate the
      distribution of CIPC between potatoes, according to the formulation used (DP, EC
      and HN), a research project financed by "le fond budgetaire des matieres
      premieres" has been set up. In order to evaluate the distribution of CIPC into
      the pile of potatoes, the efficiency of the different formulations as well as the
      residues caused by their application on tubers, some tests have been placed in
      the storage hall. These tests consist in taking off some samples at different
      places into the pile of potatoes during storage and destocking. The content of
      CIPC is analysed by capillary gas chromatography with detection by mass
      spectrometry detection (GC-MS) or nitrogen specific detection (GC-NPD). To
      estimate the efficiency, the sprouting are observed every month and samples of
      potatoes are taken off on the top of the pile to control the evolution of CIPC
      content. Considering the results of the tests, the inhibitor treatment with the
      formulation DP+HN seems to be the more efficient. As for the residues, the
      formulation DP leads to a higher content of CIPC than HN, that has a very low
      concentration. After treatment, the quantity really applied on tubers depends on
      the formulation used. In fact, 50% of CIPC applied by DP formulation are found on
      tubers but hardly 10%, after gas application.

PMID- 15151311
TI  - Simulation of drift of pesticides: development and validation of a model.
AB  - Over the last decade drift of pesticides has been recognized as a major problem
      for the environment. High fractions of pesticides can be transported through the
      air and deposited in neighbouring ecosystems during and after application. A new
      computer-two steps-drift model is developed: FYDRIMO or F(ph)Ysical DRift MOdel.
      In the first step the droplet size spectrum of a nozzle is analysed. In this way
      the volume percentage of droplets with a certain size is known. In the second
      step the model results in a prediction of deposition of each droplet with a
      certain size. This second part of the model runs in MATLAB and is grounded on a
      combination of two physical factors: gravity force and friction forces. In this
      stage of development corrections are included for evaporation and wind force
      following a certain measured wind profile. For validation wind tunnel experiments
      were performed. Salt solutions were sprayed at two wind velocities and variable
      distance above the floor. Small gutters in the floor filled with filter paper
      were used to collect the sprayed droplets. After analysing and comparing the wind
      tunnel results with the model predictions, FYDRIMO seems to have good predicting
      capacities.

PMID- 15151312
TI  - Metallothionein induction in the aquatic oligochaete Tubifex tubifex exposed to
      the herbicide isoproturon.
AB  - Metallothioneins (MTs), are low molecular weight proteins, mainly involved in
      metal ion detoxification. Recently it has been demonstrated that MTs participate
      in several cellular functions such as regulation of growth, and anti-oxidative
      defenses. Moreover, pesticides can induce their synthesis. The aim of the current
      work was to determine the effects of isoproturon either pure or formulated as
      Matin (suspension containing 500 g x l(-1) isoproturon) on the metallothionein
      and total protein content of the aquatic worm Tubifex tubifex. MT levels in
      exposed worms increased significantly after 7 and 15 days of exposure to 50 mg x
      l(-1) of herbicide. Isoproturon reduced metal (Cu, Zn, and Cd) content of
      metallothioneins, and it also increased total protein content of the worms. The
      results suggest that MT induction may not be considered as a specific biomarker
      of metal exposure but it can be used as a non specific biomarker of isoproturon
      effect in the worm.

PMID- 15151314
TI  - Effects of different factors on the residues of heptenophos in cucumber.
AB  - The present study was conducted to determine the effects of various factors on
      residues of heptenophos in cucumber under field conditions. Heptenophos (EC50)
      was sprayed at recommended close (1/1000) and double dose (2/1000). The effects
      of peeling and repeated application on residues level were also examined. Samples
      were collected at different time intervals and residues of heptenophos were
      determined using GC. Six hours after application 9.96 and 2.5 mg/kg heptenophos
      were recovered on the cucumber from the above treatments respectively. The
      residues of heptenophos in cucumber decreased rapidly in both treatments and
      reached a low level after five days (0.2 and 0.1 mg/kg respectively). Two times
      application of heptenophos caused no insecticide accumulation in cucumber. This
      investigation revealed that peeling the fruits did not reduce total residues in
      cucumber.

PMID- 15151315
TI  - Teratogenicity test of dimethoate containing insecticide formulation and Cd
      sulphate in chicken embryos after administration as a single compound or in
      combination.
AB  - Cd-sulphate and a 38% dimethoate containing insecticide formulation (BI 58 EC)
      were used as test material in a teratogenicity test in chicken after
      administration as a single compounds or in combination. The incubated chicken
      eggs were directly exposed to the applied test materials with injection into the
      air-chamber in a volume of 0.1 ml/egg before the starting of incubation. Applied
      concentration of Cd-sulphate was 0.01% and the concentration of pesticide was
      0.1%. Evaluation was done on day 19. In test of individual toxicity after
      injection on day 0 of incubation Cd-sulphate did not cause a significant
      reduction in body mass of embryos. The rate of embryonic mortality was 26%. After
      the administration of dimethoate containing insecticide formulation on day 0 of
      incubation no decrease occurred in embryonic body mass. The rate of embryonic
      mortality was 31%. The developmental anomalies observed in the different
      treatment groups occurred sporadically. The simultaneous administration of Cd
      sulphate and the dimethoate containing insecticide formulation on day 0 of
      incubation resulted in expressed embryonic mortality. The rate of embryonic
      mortality was 93%. In summary, it can be established that the simultaneous
      administration of Cd-sulphate and the dimethoate containing insecticide
      formulation on day 0 in studies of chemical interaction exerted an adverse effect
      on embryonic mortality.

PMID- 15151313
TI  - Toxicology and histopathology of some rodenticides and palatable food items
      combinations on the common mice Mus musculus var. albus in Egypt.
AB  - In this study the palatability tests of certain food items as attractants in the
      poisoned-baits for the albino mouse Mus musculus var. albus showed that the food
      items of treacle, maize oil, dry or wet sugar and milk powder act as more
      attractive pleasant materials that encourage the mice to consume more of those
      baits containing such items. The most palatable combination of tested food items
      to the mouse Mus musculus was that consisting of crushed maize + treacle + maize
      oil + milk powder. The least amount of food consumed by the mice was that of rice
      and or rice + treacle + oil + milk powder. The use of wheat grain alone was much
      better than crushed maize alone or and combined with wet or dry sugar. The tested
      anticoagulant rodenticides were greatly effective against the albino mouse Mus
      musculus var. albus, since they could cause a final mortality of hundred percent
      in a mean time ranging merely between 7 & 9 days. Chlorophacinone was more potent
      and effective than coumachlor; at its lowered concentrations of 25 and 44.5 ppm
      was more acceptable than coumachlor. The consumed amounts of zinc phosphide baits
      were comparatively utmost lower than those of anticoagulants poisoned baits.
      Feeding the pregnant females on prepared baits consisting of crushed maize,
      treacle, milk powder, maize oil and lower concentration of each of coumachlor,
      chlorophacinone and zink phosphide, to a more or less extent, reduced females
      weight according to the tested lower concentration, versus the weight of pregnant
      females in control treatment which was increased by 14.4%. In comparison to both
      the tested anticoagulant rodenticides, the measured reduction of females weight
      caused by zinc phosphide (6 ppm) was, to a more extent, higher as the mean weight
      gradually decreased from 27.4 up to 16.3 g. Chlorophacinone at its minimized
      concentrations was least effective in reducing the number and mean weight of
      developing fetuses. However, coumachlor at its tested concentration of 2 ppm
      caused abortion after the first and the second weeks of pregnancy reached to
      100%. Zinc phosphide at both tested concentrations of 0.6 and 6 ppm was
      ineffective on the abortion and resorption of fetuses; the fed females on baits
      containing 0.6 and/or 6.0 ppm zinc phosphide ate their youngsters at the 2nd and
      4th day after birth, respectively. The histopathological changes of liver,
      kidney, lung and intestine due to feeding of the Mouse Mus musculus var. albus on
      the poisoned baits of tested different rodenticides were recorded and
      photographed.

PMID- 15151316
TI  - Comparing two methods of examination in the interaction study of a pesticide and
      a heavy metal.
AB  - The use of pesticides in field application involves the risk of poisoning wild
      animals. The reproduction period of pheasant takes place at the same time as the
      spraying time of pesticides, which justifies, that we evaluate in a point of the
      ecotoxicologic view the influence of the pesticide on progressive avian embryo.
      The most frequent technical way is injecting the exam stuffs to the some part of
      the embryonated eggs under the bird teratological trials. The advantage of this
      method is that it can be injected in a correct measured dose into the optional
      part of eggs. The disadvantage of this method is that it can't model properly the
      influence on the environment. If adverse effect of the embraced chemical
      substance on the embryo is experienced under the study, it will be necessary to
      use an immersion treatment. This procedure shows only the possible indirect
      influence of the pesticide on the embryo but it can suitably model its influence
      in plant protection practice. Treatment was done on day 12 of incubation. Applied
      concentration of heavy element (Cd sulphate) was 0.01% and the concentration of
      pesticide (Dithane M-45) was 0.2%. Evaluation was done on day 19 of incubation.
      Injection treatment: the simultaneous administration of Cd sulphate and the 80%
      mancozeb containing fungicide formulation on day 12 of incubation did not result
      in a significant decrease in the average body weight of embryos compared to
      neither the control nor the pesticide individually treated group. At the same
      time the body weight of embryos significantly decreased because of combined
      administration as compared to the Cd sulphate treated group. The embryo mortality
      and the incidence of developmental anomalies markedly increased after the
      simultaneous administration. Immersion treatment: the combined administration of
      Cd sulphate and the mancozeb containing fungicide formulation on day 12 of
      incubation did not result in a significant decrease in the average body mass of
      embryos compared to neither the control nor the individually treated groups. The
      number of embryo mortality was very high after the simultaneous administration.
      The incidence of developmental anomalies was sporadic.

PMID- 15151318
TI  - Toxicity and degradation of metolachlor (Dual Gold 960 EC) in chicken embryos.
AB  - The herbicide formulation Dual Gold 960 EC (960 g/l metolachlor) was applied,
      ROSS 308 embryonated hen eggs were treated on day 12 of incubation period. The
      pesticide was diluted in water to a concentration level 0.3% and the emulsion was
      injected into the air space in a volume of 0.1 ml/egg, or hen's eggs were treated
      by the immersion technique (30 min). Residues of metolachlor were measured by GC
      in 14 collected embryo samples on days 13, 15 and 19 of the incubation of chicken
      embryos, and macro- and microscopic morphological examinations of 49 embryos were
      performed simultaneously on day 19. Body mass of embryos was weighed on 13th,
      15th and 19th day of incubation. After the both treatments the mortality rate of
      embryos was similar. The average data of body mass showed a significant decrease
      compared to the control in the immersion study on day 15 and 19 of the hatching
      period. This phenomenon may only be in connection with the presence of
      metolachlor over the limit of quantification (LOQ) on day 13 of incubation
      period. The macroscopic deformations were sporadic in the embryos. No
      histologically detected alterations were seen.

PMID- 15151317
TI  - Embryonic toxicity of a mancozeb containing fungicide formulation and Cu-sulphate
      in pheasant after individual or combined administration.
AB  - Cu-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45)
      were studied in pheasants after administration as single compounds or in
      combination. The test materials were injected directly into the air-chamber of
      eggs on day 12 of the hatching period and evaulation was carried out on day 23 of
      incubation. The pheasant embryos were examined for the following: rate of embryo
      mortality, body mass, type of developmental anomalies, light microscopic
      examination. After the administration of copper-sulphate on day 12 of incubation,
      the average body weight of pheasant embryos significantly did not decrease as
      compared to the control. The embryonic mortality was 68%. After the
      administration of a mancozeb containing fungicide formulation (Dithane M-45) on
      day 12 of incubation, the average body weight of embryos did not decrease as
      compared to the control. The embryonic mortality was 50%. After the individual
      administration of pesticide, the incidence of developmental anomalies was very
      high. After the combined administration of copper-sulphate and the 80% mancozeb
      containing fungicide formulation (Dithane M-45) on day 12 of incubation the
      embryonic mortality markedly increased. The rate of embryo mortality was 93%. We
      did not find any degenerative change in the liver tissue in either the control
      group or the treated groups by light microscopic examination. In summary, it can
      be established that the simultaneous administration of Cu-sulphate and mancozeb
      containing fungicide formulation caused high toxicity compared with the
      individual toxicity of test materials.

PMID- 15151320
TI  - Natural specific radioactivity in different soils. Transfer in the soil plant
      food chain.
AB  - In order to warrant customer's health we must pay attention to the quality of the
      environment and production processes; that means look all over alimentary chain.
      Media speak often about this topics, because of the interest of the public
      opinion regarding agribusiness; Nether the less much is know about soil
      radioactivity, but often scant attention is directed to the knowledge of the
      amount what remains in food and arrives to the man who is the last and main user
      of the product. As a consequence of that, we have done some originals studies
      concerning specific radioactivity in alimentary chain: soil-plant-food. These
      studies have been made in relation with geopedologic position of fields in
      volcanic, clayey, sandy soils of Latium. We have measured radioactive activity
      over some alimentary chains both annual (like turnip and garden cress) and
      pluriannual (such as vine). We made comparisons on the same soils studying the
      following natural markers: K40, Pb214, and Bi214; and Cs137, one of the main
      natural markers.

PMID- 15151319
TI  - Toxicity of a mancozeb containing formulation and Cd-sulphate to chicken embryos
      after administration as single compounds or in combination.
AB  - Environmental pollution of metal modelled by cadmium-sulphate and a 80% mancozeb
      containing fungicide formulation (Dithane M-45) were studied on chicken embryos
      after administration as a single compounds or in combination. The test materials
      were injected into the air-chamber in a volume of 0.1 ml/egg on day 0 of
      incubation. The concentration of cadmium-sulphate was 0.01%. The applied
      concentration of Dithane M-45 fungicide was 0.2%. Evaluation was done on day 19
      of the hatching period. The individual administration of cadmium-sulphate and the
      80% mancozeb containing fungicide formulation did not cause a significant
      reduction in body weight as compared to the control data. Embryonic mortality
      increased at all individual treated groups and reached almost a 35% rate. After
      the individual administration of pesticide, the number of chicken embryos with
      developmental anomalies did not differ markedly from the control. After the
      combined administration of cadmium-sulphate and the 80% mancozeb containing
      fungicide formulation (Dithane M-45) on day 0 of the hatching period embryonic
      mortality markedly increased. 88% of the treated embryos were dead. Results from
      the combined administration of cadmium-sulphate and an 80% mancozeb containing
      fungicide formulation (Dithane M-45) caused higher embryomortality with respect
      to individual toxicity test of cadmium-sulphate and fungicide in our study.

PMID- 15151321
TI  - Copper as indicator of agroenvironmental effects of various crop protection
      techniques used in Lazio, Italy. Verification in the areas of Maccarese,
      Terracina and Cisterna of Latina.

PMID- 15151322
TI  - Organic viticulture: efficacy evaluation of different fungicides against
      Plasmopara viticola.
AB  - The restriction on the use of copper salt fixed by the European Community (Reg.
      EC n. 473/2002) owing to the environment problems due to the copper accumulation
      in the soil, has stimulated the research to evaluate the possibility to reduce
      the copper use. This field experiment was carried out to estimate, in an organic
      vineyard, the effectiveness, against Plasmopara viticola (Berk. et Curt) Berl. et
      De Toni, of copper compounds at a low rate or alternative copper products.
      Guideline EPPO/OEPP PP 1/3 (2) has been used. Plots of 18 plants each, repeated 4
      times in a randomized design, have been arranged. The obtained results, even if
      related to circumscribed and extremely favorable field for the development of the
      grapevine downy mildew, evidenced the impossibility to practice a defense to
      fixed cadence, succeeding, at the same time, to respect the limits of European
      Community for copper metal. The reference product, that has guaranteed the best
      results, determined a total contribution of copper metal of 25.7 Kg/ha that
      leaves very little possibilities of copper use in the following years, like
      previewed from the Reg. EC n. 473/2002; therefore a strategy of defense of this
      type turns out as not usable. The two cupric products characterized by the low
      metallic content were not completely satisfactory in our operating conditions
      with high pressure of grapevine downy mildew, but they determined a contribution
      of copper metal under the limits established by the European Community. Therefore
      new experiments, using differentiated strategies, should be carried out to
      improve the effectiveness of these fungicides. About biofungicide, it gave total
      absence of biological activity against P. viticola. The limits of the used
      formulations regarding the operating protocol applied, are evidenced, for some of
      them, by epidemiological results, for the others by the high amount of
      distributed copper, that causes an accumulation of residual in soil and leaves.
      Through the examination of the results and considering the particular climatic
      condition that characterized 2002, we can conclude that the trial must be
      considerate valid for the stressful situations that affected the vineyard.

PMID- 15151323
TI  - Methods to reduce the emission of pesticides on farm level.

PMID- 15151324
TI  - Atlas of pesticide concentrations in Dutch surface waters: a pilot study.
AB  - A pilot study was conducted to explore the potential for geographically mapping
      concentrations of individual pesticides in Dutch surface waters and compiling
      these maps into a National Pesticide Atlas. This atlas could be used for various
      purposes: 1) To see where specific pesticides are monitored, observed and find
      out whether these are problematical. 2) To explore the relationship between
      environmental pesticide levels and land use, using the results as feedback to
      improve national pesticide admission procedures (post-registration review) 3) To
      review the quality of the present Dutch pesticide monitoring system. For the
      study we used measured data for the years 1997 and 1998, preparing maps for six
      illustrative pesticides. The data are presented on a grid scale of 5x5 km2.
      Pesticide concentrations are compared with three standards: the EU drinking water
      standard, the maximum tolerable risk (MTR) level and the admission standard set
      by the Dutch Pesticide Admission Board (CTB). The results show that all these
      pesticides can be satisfactorily mapped at the national level and that for most
      of the compounds investigated a useful relationship can be established between
      environmental concentration and land use. The maps also serve to show up gaps in
      the present pesticide monitoring system. The study yielded several new insights,
      among them that standards were found to be exceeded in areas and at times of the
      year not anticipated on the basis of land use and pesticide use statistics. As a
      follow-up to this pilot study a new project has been started to develop an
      internet version of the pesticide atlas for all measured pesticides in The
      Netherlands.

PMID- 15151325
TI  - Presence of plant protection products in three agricultural areas of Regione
      Lazio.
AB  - Aim of the research was to verify the impact of plant protection products on
      three significant agricultural areas of Regione Lazio: Maccarese, Cisterna di
      Latina, Sabaudia-Terracina. This research studied the presence of some active
      ingredients, indicated by technicians as distributed, on soil, water, crop and
      air samples, the last one in greenhouse; the analysis, carried out by multi
      residue methods, allowed to investigate also on a large amount of active
      ingredients not indicated by technicians. The determinations have been obtained,
      using internal standards, by GC-NPD, GC-ECD, HPLC-UV, HPLC-DAD, with different
      columns, conditions and wavelength of adsorption. Taking into account the results
      we could to assert that only a small part of the molecules searched were found in
      the samples and that they are typical for the crops and the environment treated.
      In greenhouse, more persistence was founded in wood greenhouse, treated from the
      outside, probably for the release of a.i. in time from wood and for a better
      distribution. The active ingredients more frequently founded must be controlled
      to avoid possible accumulation or leaching, especially for herbicides in the
      areas of Maccarese and Cisterna di Latina. Furthermore, the molecule on which
      more attention must be done when applied, are: linuron on carrots, penconazole on
      zucchini and cymoxanil, often used inappropriately, particularly on minor crops,
      like red-radish. Although the number of sampling was limited, it has been
      possible to outline the situation in the three zones considered, for directing
      choices, that could be more sensible at sanitary spin-off and at the environment.

PMID- 15151326
TI  - Residues of trichlorfon and its metabolite dichlorvos in olive, oil, waste water.

PMID- 15151327
TI  - Biohazards and ecotoxicological considerations of landspreading of spent compost
      wastes.
AB  - Spent mushroom compost (SMC) is a major waste of the mushroom industry with low
      economic value. SMC arises after mushroom production in phase II compost (pIIC),
      predominantly comprising straw and chicken litter as principal raw ingredients.
      The majority of SMC waste is disposed off by application to agricultural land. It
      is an attractive proposition for utilising SMC as soil inorganic fertiliser
      supplementation. However, there is limited data available as to the consequences
      of this method of disposal either in terms of microbiological loading of food
      borne pathogens and those of concern to mushroom industry itself. The resulting
      imbalance of the natural flora of the agricultural land has not been properly
      audited. This study aims to initially examine SMC for prevalence of faecal
      bacterial pathogens including Campylobacter spp., Salmonella spp. and Listeria
      monocytogenes that may arise from chicken litter. At another level, it aims to
      ascertain the pathogenic bacteria (Pseudomonas syringae, pv phaseolicola or
      tolasii) and fungal populations (Trichoderma, Verticillium species) originating
      mainly from the straw component of the SMC, which are of concern to the mushroom
      industry. Lastly, the study would also qualitatively identify the diversity of
      bacterial populations within SMC. This was largely accomplished through
      employment of rDNA, PCR and direct sequencing strategies on the culturable
      microflora. However, for specific mushroom pathogens, nucleic acids (DNA or RNA)
      were directly extracted from composts before subjecting to sequence analysis. In
      accordance with the current legislation (ABP 02/02, Animal By Products wastes
      disposal EC No. 1774/2002), it is imperative to regulate the farm wastes carrying
      residues from animal sources including SMC before they are regarded safe for land
      spreading operations. The ecological microbe-microbe and plant-microbe
      interactions that potentially occur between the native bacterial soil flora and
      those added annually (approximately 10(18) cells) needs to be reviewed with
      caution. The above study highlights the ecological consequences involved in the
      disposal of SMC wastes on agricultural land and its implications for plant,
      animal and human health.

PMID- 15151328
TI  - Post emergent spraying demands, opportunities and benefits in field crop spraying
      practice.

PMID- 15151329
TI  - Optimisation of a vertical spray boom for greenhouse spraying applications.
AB  - The European Crop Protection Association (ECPA) and CLO-DVL joined forces in a
      project to stimulate a safe use of pesticides in Southern European countries. CLO
      DVL optimised a method with mineral chelates to evaluate deposition tests. This
      quantitative method to evaluate spray deposits and to check spray distributions
      is used to assess two novel spraying techniques. Deposition tests with water
      sensitive paper and mainly with the manganese and molybdenum chelates as tracer
      elements were performed with a manually pulled trolley and a motorised vehicle
      both equipped with vertical spray booms. Filter papers were attached to the
      tomato and pepper plants at several heights to obtain an indication of the spray
      distribution in the crop. Particular attention was paid to the effect on the
      spray distribution of the vertical nozzle distance (35 cm vs. 50 cm) and the
      spray distance to the crop. The tests proved that a nozzle spacing of 35 cm
      delivers a much better spray distribution than one of 50 cm. The optimal spray
      distance for flat fan nozzles with a spray angle of 80 degrees and a nozzle
      spacing of 35 cm is about 30 cm.

PMID- 15151330
TI  - Efficacy and safety assessment of a new liquid tooth whitening gel containing
      5.9% hydrogen peroxide.
AB  - PURPOSE: To evaluate the efficacy and safety of a new 5.9% hydrogen peroxide
      liquid, invisible gel, (Colgate Simply-White Whitening Gel). METHODS: A total of
      30 subjects were enrolled into the study and divided into two treatment groups
      (Colgate vs. placebo gel). Efficacy was assessed using VITA shade scores and
      safety evaluations were performed including the examination of plaque index (PI),
      bleeding index (BOP), gingival recession and dentin hypersensitivity. Statistical
      analysis was performed to determine the mean change from baseline. RESULTS: The
      new whitening gel containing 5.9% hydrogen peroxide was significantly effective
      in lightening tooth shade. After only 2 weeks, patients enrolled in the study
      exhibited an overall mean 4.48-shade improvement from baseline, which was
      significantly greater than placebo group and far exceeded the ADA minimum
      requirements to claim "clinical efficacy". In the new Colgate Simply White Clear
      Whitening Gel group, periodontal health (PI and BOP) improved with time overall.
      Moreover, dentin hypersensitivity did not significantly increase, and all
      treatments were generally well tolerated. CLINICAL SIGNIFICANCE: The new Colgate
      Simply White whitening gel containing 5.9% hydrogen peroxide allowed consistent
      bleaching using minimal contact time, without adversely impacting overall
      tolerability.

PMID- 15151331
TI  - Cleaning power and abrasivity of a new toothpaste based on ion-exchange resins.
AB  - PURPOSE: To compare the stain removal efficacy and enamel abrasivity of a new
      experimental dentifrice based on an ion-exchange resin mixture that releases
      calcium, fluoride, phosphate and zinc ions (named NMTD1), to four commercially
      available dentifrices: Crest Extra-whitening toothpaste, Crest Tartar Protection
      toothpaste, Crest Cavity Protection toothpaste and Colgate Fluoride Cavity
      Protection toothpaste. Calcium pyrophosphate was used as a control for the
      efficacy of the staining removal experiment. METHODS: Cleaning power evaluation
      was made following the method developed by Stookey et al. The abrasion of the
      toothpastes was determined by means of a brushing machine, using 2000, 4000 and
      8000 strokes and a 250g toothbrush load. Bovine specimens were prepared and
      abrasion was measured by a surface profilometer system. RESULTS: The new
      experimental dentifrice did not remove stains whereas Crest Extra-whitening and
      Crest Cavity Protection dentifrices produced statistically significant stain
      removal when compared with the calcium pyrophosphate control. Abrasion studies
      demonstrated that abrasion was linearly correlated to the number of strokes and
      the abrasion rates proved to be non significant for Colgate and the new
      experimental dentifrices, but significant for Crest Extra-whitening, Crest Tartar
      Protection and Crest Cavity Protection. CLINICAL SIGNIFICANCE: This study
      demonstrated that the use of a dentifrice based on an ion-exchange mixture was
      not effective at removing stains and abrasion was most insignificant when
      compared to other commercially available toothpastes.

PMID- 15151332
TI  - Effect of 1000 ppm relative to 250 ppm fluoride toothpaste. A meta-analysis.
AB  - PURPOSE: To estimate the overall effect of 1000 ppm F relative to 250 ppm F
      toothpaste. METHODS: Experimental caries increment studies from the dental
      literature, which compared 1000 ppm with 250 ppm fluoride toothpastes, were
      summarized using meta-analytic methods. RESULTS: The overall caries reduction of
      1000 ppm F relative to 250 ppm F paste was estimated to be 0.142 (95%-CL: 0.074
      0.210) when applying a fixed effects model and 0.129 (95%-CL: 0.012-0.230) when
      applying a random effects model. CLINICAL SIGNIFICANCE: The present analysis
      found slightly lower caries increments (14%, 13%) in children using 1000 ppm F
      toothpastes compared to children using 250 ppm F pastes. On the other hand, the
      use of 1000 ppm F pastes is associated with dental fluorosis. Considering these
      effects it seems justifiable to the authors to keep the use of 250 ppm F pastes
      for preschool children in Switzerland.

PMID- 15151333
TI  - Bonding to root caries by a self-etching adhesive system containing MDPB.
AB  - PURPOSE: To evaluate the bonding of an experimental antibacterial fluoride
      releasing adhesive system (ABF) to normal and carious dentin in human teeth with
      Class V root caries. METHODS: Mesiodistal sectioning removed the buccal enamel,
      superficial dentin and much of the carious dentin in 21 extracted human bicuspids
      with root surface caries. The surfaces of normal coronal and root dentin, and
      caries-affected and caries-infected dentin were ground with wet 600-grit SiC
      paper to create a standardized smear layer. Tooth surfaces were treated with the
      ABF according to manufacturer's instructions, and then covered with excess resin
      composite. After immersion in 37 degrees C water for 24 hours, the restored teeth
      were horizontally sectioned into serial slabs that were trimmed into hourglass
      shapes to isolate the bonded area to the test substrates, and then their bond
      strengths were measured by the microtensile bond test, and the interfaces
      examined by SEM and TEM. The bond strengths were statistically compared with
      ANOVA and Fisher's PLSD (P < 0.05). RESULTS: The bond strengths of ABF to caries
      affected and caries-infected dentin were significantly lower than those to normal
      coronal and root dentin. SEM micrographs revealed that the hybrid layers in
      caries-affected and caries-infected dentin were more porous compared to the
      hybrid layer in normal coronal and root dentin. TEM micrographs showed that
      bacteria that had invaded the dentin were embedded in this adhesive monomer in
      caries-infected dentin. CLINICAL SIGNIFICANCE: Although the bond strength of ABF
      adhesive system to root carious dentin is lower than that of normal dentin, the
      antibacterial and fluoride-releasing properties of ABF may contribute to prevent
      caries progression and inhibit secondary caries.

PMID- 15151334
TI  - Clinical criteria used to detect primary root caries with electrical and
      mechanical measurements in vitro.
AB  - PURPOSE: To relate the Electrical Caries Monitor (ECM) and Resilience Caries
      Monitor (RCM) readings with clinical criteria used to define primary root carious
      lesions (PRCLs) in vitro. METHODS: PRCLs were classified according to color,
      texture, hardness, cavitation, size and severity before ECM and RCM readings were
      recorded. RESULTS: There was a poor but significant correlation between the ECM
      and RCM phase readings (P < 0.05). ECM readings for color, all five classes of
      severity and all three classes of hardness of lesions were significantly
      different from each other and from sound root tissue (P < 0.05). There was a
      significant correlation for ECM readings and cavitation (P < 0.05). There was a
      clear logarithmic relationship between ECM end values and size (P < 0.05). RCM
      amplitude measurements for hardness and all five classes of severity were
      significantly different from each other and from sound root tissue (P < 0.05).
      However, the RCM readings failed to correlate with color, cavitation or size (P >
      0.05). In conclusion, the relationship between ECM and RCM data and some clinical
      detection criteria for PRCLs is promising and warrants further investigation in
      vitro and in vivo. CLINICAL SIGNIFICANCE: The ECM is capable of distinguishing
      the severity of PRCLs since it is a less invasive but accurate method of
      detecting carious lesions when compared to tactile methods. The RCM was able to
      differentiate sound root dentine from soft lesions in vitro but this device is
      currently in a very early stage of development, and many mechanical and
      electronic problems must be solved prior to application of the device in clinical
      practice.

PMID- 15151335
TI  - Effect of two different restorative techniques using resin-based composites on
      microleakage.
AB  - PURPOSE: To evaluate in vitro the extent of microleakage of Class II cavities
      restored with two different brands of resin-based composite, one hybrid (Tetric
      Ceram) and the other "packable" (Surefil) taking into account two variables: the
      localization of the margins and the insertion technique. METHODS: 100 bovine
      teeth, recently extracted, had standardized Class II slot cavities prepared on
      the mesial and distal surfaces with the gingival floor located on enamel or
      dentin, for a total 200 cavities. The teeth were randomly divided into eight
      groups of 25 teeth each (25 restorations in each group): (1) margin on dentin,
      restored with Surefil, bulk insertion; (2) margin on dentin, restored with Tetric
      Ceram, bulk insertion; (3) Margin on enamel, restored with Surefil, incremental
      technique; (4) margin on enamel, restored with Tetric Ceram, incremental
      technique; (5) margin on enamel, restored with Surefil, bulk insertion; (6)
      margin on enamel, restored with Tetric Ceram, bulk insertion; (7) margin on
      dentin, restored with Surefil, incremental technique; (8) margin on dentin,
      restored with Tetric Ceram, incremental technique. After this procedure, the
      teeth were subjected to 1000 thermocycles, stained with 2% methylene blue
      solution, and then sectioned in the mesiodistal direction. Dye penetration at
      tooth/restoration interface was scored based upon the extent of the dye using a
      light stereoscope x 35. RESULTS: All groups showed considerable levels of
      microleakage at both dentin and enamel margins (P < 0.05). Restorations with
      margins in enamel using the hybrid resin-based composite with the incremental
      technique did not show statistically significant differences when compared to
      bulk placement. However, restorations with hybrid resin-based composite have
      significantly less microleakage than either bulk or incremental technique for the
      "packable" resin-based composite Surefil. As for the margins in dentin, Tetric
      Ceram in bulk placement did not differ from the incremental technique and Tetric
      in bulk placement had significantly less microleakage than Surefil either bulk or
      incremental technique. The hybrid resin-based composite with margins in dentin
      and incremental technique showed less microleakage than the "packable" resin in
      bulk placement. CLINICAL SIGNIFICANCE: The two types of resin-based composites,
      hybrid and "packable" were unable to completely prevent microleakage. The study
      demonstrated the difficulty in sealing a proximal margin.

PMID- 15151336
TI  - Effects of storage media on mechanical properties of adhesive systems.
AB  - PURPOSE: To evaluate the effects of water vs. oil storage on the mechanical
      properties of dental adhesives over 3 and 6 months. METHODS: Adhesive resin
      sheets were prepared by pouring either Single Bond (SB), One-Step (OS) or
      Clearfil Liner Bond 2V (CL) into a mold measuring 15 x 15 x 0.8 mm. After solvent
      evaporation, the adhesives were light-cured, removed from the mold and trimmed to
      either hourglass or I-beam shapes that were used to determine the true stress
      (TS) and modulus of elasticity (E), respectively. Control adhesive specimens were
      subjected to tensile testing at 0.6 mm/minute after 24 hours of immersion in
      distilled water. Experimental specimens were stored at 37 degrees C in either
      distilled water or mineral oil and tested after 3 and 6 months. The data were
      analyzed by two-way ANOVA and Tukey's test. RESULTS: Storage in water
      significantly decreased the TS and E of SB and OS specimens after 3 and 6 months
      (P < 0.05), but did not cause significant changes in either TS or E of CL
      specimens in the same periods (P > 0.05). Storage in oil significantly increased
      the TS of the three adhesives after 3 and 6 months (P > 0.05), and the same trend
      was observed for E value of CL sample (P > 0.05). CLINICAL SIGNIFICANCE: Exposure
      of cured adhesive systems to long-term immersion in water caused marked reduction
      in their mechanical properties. Reduced mechanical properties of the adhesive
      system may compromise resin/dentin bonds and have a clinical implication on the
      longevity of adhesive restorations.

PMID- 15151337
TI  - Surface roughness of resin composite prepared by single-use and multi-use
      diamonds.
AB  - PURPOSE: To compare the surface roughness of a resin composite caused by two 30-
      and 40-microm, multi-use finishing diamonds with two 30- and 40-microm, single
      use finishing diamonds of comparable grit size before and after steam
      sterilization. METHODS: Resin composite specimens 6 mm in diameter and 3 mm in
      depth were light cured. Surface roughness (Ra, microm) of surfaces formed by
      Mylar, after finishing with a bur, and after polishing with fine and superfine
      aluminum oxide disks was measured for the as-received and after sterilization
      conditions with a surface profilometer. RESULTS: Ra of Mylar surfaces (baseline)
      ranged from 0.02-0.05 microm. Ra of surfaces prepared with 30-microm diamond burs
      ranged from 1.42-1.90 microm. Ra of surfaces prepared with 40-microm diamond burs
      ranged from 2.22-2.42 microm. Ra of surfaces polished sequentially with fine and
      superfine aluminum oxide disks ranged from 0.07-0.11 microm in the as-received
      condition and from 0.12-0.14 microm in the sterilized condition. Sterilization
      and reuse of all types of diamond finishing burs resulted in equal or rougher
      resin composite surfaces after final polish when compared to final polish
      surfaces that were initially finished with as-received diamonds. CLINICAL
      SIGNIFICANCE: Surface roughness of a resin composite prepared with single- and
      multi-use diamond finishing burs was equivalent when compared at the final
      polish.

PMID- 15151338
TI  - Comparison of PAC and QTH light sources on polymerization of resin composites.
AB  - PURPOSE: To evaluate the polymerization shrinkage, Knoop hardness number (KHN)
      and compressive strength and to suggest a suitable time for irradiating resin
      composite restorations, when using a high-intensity light source. METHODS: Two
      restorative resin composites, UniFil F, and Clearfil AP-X were employed. A high
      intensity light unit (more than 1000mW/cm2) with a xenon discharge lamp (Apollo
      95E), which is generally called a plasma arc light-curing unit (PAC), was
      compared with a conventional light-curing unit fitted with a quartz-tungsten
      halogen lamp (QTH) (GC Newlight VL2). The resin composites were exposed to the
      light in four ways. For QTH, the irradiation time was for 40 seconds (QTH 40
      seconds). For PAC, 3 seconds (PAC 3 seconds), 3+3 seconds (PAC 3+3 seconds) and
      3+3+3 seconds (PAC 3+3+3 seconds) was used. Polymerization shrinkage using the
      bonded disk technique developed by Watts, Knoop hardness number (KHN), and
      compressive strength were then determined. RESULTS: Two-way ANOVA revealed that
      the two materials for PAC 3+3 seconds and PAC 3+3+3 seconds made no difference in
      polymerization shrinkage compared to QTH 40 seconds (P < 0.001). The
      polymerization shrinkage of the materials cured by PAC for 3 seconds was
      significantly lower than those cured by QTH for 40 seconds in a range from 61% to
      72%, by the PAC for 3 + 3 seconds in a range from 65% to 88%, and those by PAC
      3+3+3 seconds in a range of 61% to 72% (P < 0.001). With regard to microhardness,
      the composites in PAC 3+3+3 seconds exposure made no difference in hardness
      compared with QTH 40 seconds (P < 0.001). PAC 3+3 seconds exposure gave hardness
      at less than 3.0 mm depth equivalent to that of the QTH 40 seconds. PAC 3 seconds
      at 2.0 mm depth produced inferior hardness compared with the QTH 40 seconds. The
      compressive strength for the PAC 3 seconds exposure was significantly lower than
      that of PAC 3+3 seconds, PAC 3+3+3 seconds and QTH 40 seconds for each material.
      CLINICAL SIGNIFICANCE: Irradiation by the high-intensity light source for 3
      seconds provided significantly lower microhardness and compressive strength for
      light-cured resin composites. The 3+3+3 seconds repeated irradiation with the PAC
      unit and QTH 40 second values were not significantly different.

PMID- 15151339
TI  - Microleakage around a low-shrinkage composite cured with a high-performance
      light.
AB  - PURPOSE: To compare microleakage of Class V restorations filled with a novel low
      shrinkage resin-based composite cured by a high intensity light and a combination
      of controls including a conventional composite cured by conventional and soft
      start regimes. METHODS: Forty-two intact premolar and molar teeth were randomly
      assigned to seven groups and filled with a low-shrinkage composite or a
      conventional composite, bonded with one of two bonding materials (Excite or
      Prime&Bond NT) and cured with either a high intensity light, a soft-start regime
      or a conventional light regime. Cavities were cut in both the buccal and lingual
      aspects of each tooth with half of the preparation in enamel and half in
      dentin/cementum. The teeth were thermocycled and the restorations examined
      microscopically for leakage using Procion Brilliant Red as a marker. RESULTS:
      None of the groups showed microleakage at the enamel margins. All groups showed
      leakage at the gingival margins. At the gingival margins there was no significant
      difference between the low-shrinkage composite, bonded with the manufacturer's
      adhesive, and cured by high intensity regime, and the conventional composite
      bonded by the manufacture's adhesive and cured by one of two soft start regimes.
      Nor was there a significant difference between the low-shrinkage composite,
      bonded by the manufacturer's adhesive and cured by either the high intensity
      regime or one of two soft start regimes. The low-shrinkage material, bonded by
      the manufacturer's adhesive and cured by the high intensity regime showed
      significantly less microleakage than the conventional composite, bonded by the
      manufacturer's adhesive and cured with a conventional light source. CLINICAL
      SIGNIFICANCE: Gingival marginal microleakage is not prevented by the use of a low
      shrinkage composite cured by a high intensity light. If time were an essential
      consideration, the low shrinkage composite cured by a high intensity regime may
      offer clinical advantages.

PMID- 15151340
TI  - Bond strengths of repaired laboratory composites using three surface treatments
      and three primers.
AB  - PURPOSE: To determine the in vitro bond strength of three laboratory composites
      repaired with their corresponding direct repair composites using various
      combinations of surface treatments and primers. METHODS: The effects of three
      surface treatments (600-grit as a control, air abrasion with 50-microm Al2O3
      particles and 8% hydrofluoric acid etching) and three primers with different
      formulations [Artglass Liquid (resin/silane), Sculpture Thinning Liquid (resin),
      and Targis Wetting Agent (silane)] were studied on three laboratory composites
      (Artglass, Targis and Sculpture). Specimens were stored for 24 hours at 37
      degrees C and 100% relative humidity. Tensile bond strengths were determined on
      an Instron universal testing machine at a crosshead speed of 0.5 mm/minute at
      room temperature, keeping the specimens moist throughout the testing procedure.
      RESULTS: Three-way analysis of variance (SuperANOVA) indicated that in general,
      8% hydrofluoric acid produced the highest bond strengths when used to prepare the
      three laboratory composites. Either 8% hydrofluoric acid or air abrasion with
      Al2O3 particles produced the strongest repair bond strengths for Tetric Ceram
      when used with the resin/silane primer (Artglass Liquid) with values ranging from
      36.9 to 39.6 MPa., respectively, as did the combination of hydrofluoric acid and
      the silane primer (Targis Wetting Agent) 38.2 MPa. The 8% hydrofluoric acid
      produced the highest bond strengths when used to prepare Artglass and Sculpture
      and used with the resin/silane primer, 32.9 and 38.7 MPa, respectively. Most bond
      failures (65%) were adhesive between the laboratory and repair composites,
      followed by cohesive failures in the laboratory composite with Artglass/Charisma
      and Targis/Tetric Ceram; and cohesive in the repair composite with
      Sculpture/Sculpt-It. Overall, the resin/silane primer produced the highest repair
      bond strengths for Al2O3- and hydrofluoric acid-treated composites. CLINICAL
      SIGNIFICANCE: Air abrasion and hydrofluoric acid etching offer acceptable bond
      strengths for laboratory composites repaired with direct repair composites.
      Repair bond strengths are enhanced by the application of a resin/silane primer.

PMID- 15151341
TI  - Translucency of opaque-shade resin composites.
AB  - PURPOSE: To measure the translucency parameter of opaque-shade resin composites.
      The secondary purpose was to evaluate the ability of the materials to mask dark
      background color. METHODS: CIELAB coordinates (L*, a*, b*) of three resin
      composites: UniFil S (UF), Palfique Estelite (PE), and Filtek A110 (FA) were
      determined in two shades (Opaque A3 and A3) at 1 mm and 2 mm thickness on a white
      backing, a backing of material itself and a black backing using a colorimeter.
      From the L* a* b* of 2 mm thick specimens on the white and black backing,
      translucency parameter (TP) were calculated for each material and shade to
      evaluate opacity of the materials. In addition, CIELAB color differences
      (deltaE*) were also calculated from the L*, a*, b* of 1 mm and 2 mm thick
      specimens on the material itself and on black backing, in order to estimate
      effectiveness of the resin composite materials to mask dark background color. If
      the calculated deltaE* were above 2, color differences were estimated as
      "perceptible." RESULTS: The TP values of Opaque A3 shade resins were lower than
      those of A3 resins for all the materials evaluated. When comparing the materials
      used, the Opaque A3 shade of FA indicates a higher TP value than those indicated
      for the Opaque A3 shade of the other two materials, while the A3 shade of FA
      revealed a higher TP value than the A3 shade of UF. As for the deltaE* values,
      the deltaE* recorded for 1 mm-thick specimens were in the range of "perceptible"
      and larger than those of 2 mm specimens, regardless of the shades and materials.
      For the 2 mm specimens, all of the deltaE* values for the Opaque A3 shade were
      classified as "imperceptible," whereas all deltaE* values for A3 shade were
      evaluated as "perceptible." CLINICAL SIGNIFICANCE: The opaque-shade resin
      composites were less translucent than the usual composites. Hence, if a
      restoration was relatively thick, the opaque-shade resin composites might
      effectively mask the dark background color from the oral cavity. However, if a
      restoration was relatively thin, the opaque-shade resin composites could not mask
      the dark background color as well as the usual composites. Therefore, clinicians
      should take into consideration the effect of dark background color in the shade
      matching procedure for a relatively thin restoration, even if opaque-shade resin
      composite is used.

PMID- 15151342
TI  - Quantitative evaluation of self-etching primer action on dentin permeability: a
      correlation between impedance measurements and acidity.
AB  - PURPOSE: To evaluate quantitatively the effect of six contemporary self-etching
      systems on dentin permeability by means of the electrochemical impedance
      technique and to correlate these results with their acidity. METHODS: 36 1.1 mm
      thick dentin disks were embedded in a hollow polyurethane resin cylinder. The
      system used was a "like" permeation cell: two electrodes immersed in a 10(-1) KCl
      solution were attached to a potentiostat. It was connected to a microcomputer
      controlled frequency response analyzer, and a 10 mV sinusoidal voltage signal
      over a frequency range of 1 Hz to 65 kHz was applied between the electrodes. The
      current passing through the dentin was measured to enable a calculation of
      impedance expressed in a complex number. To establish an evaluation of
      permeability variation, the resistance was noted for all specimens before and
      after the application of self-etching adhesive. A pH meter used with a combined
      glass-electrode measured the pH of all the systems. RESULTS: The higher decrease
      of the resistance of dentin samples was obtained with Experimental (EXP), which
      presented no significant difference with Touch and Bond (TB), Etch and Prime 3.0
      (EP), and Etch Free Tenure (EF). These acidic monomers improved the dentin
      permeability respectively to 6.7, 5.1, 5.0 and 5.0%. The lowest values were
      obtained with Clearfil SE Bond (SEB) (2.0%), which showed significant difference
      with all the other systems. Prompt L-Pop (PLP) with 4.3% showed significant
      difference with EXP and SEB and no significant difference with the three other
      systems. The pH and permeability variation were not systematically correlated.
      CLINICAL SIGNIFICANCE: Significant differences, in terms of quantitative
      evaluation of demineralization for self-etching systems on dentin, are of
      interest to clinical practitioners. Dentin bonding efficiency for this sort of
      adhesive system is not specifically related to this parameter, but low
      aggressiveness could be an area of concern on enamel.

PMID- 15151343
TI  - Effects of application techniques and fissure types on the in vitro performance
      of two fissure sealants.
AB  - PURPOSE: To evaluate the effect of two materials, modified applications, moisture
      contamination and fissure types on the microleakage and penetration ability of
      fissure sealants. METHODS: 140 extracted human molar teeth were randomly assigned
      to 14 groups. The three following factors were tested: 1) two sealing materials
      (Concise and Tetric Flow), 2) four modified applications (cleaning with an air
      polishing device, etching with a vibration system, the use of drying agent and
      sealant application with a vibration system), 3) the procedures performed under
      two conditions (at ambient room condition and in a humidity chamber). Each tooth
      was subjected to thermal cycling (5000 cycles at 5-55 degrees C) and dye
      immersion (5% Methylene blue for 24 hours). After sectioning, microleakage,
      penetration ability and fissure type were examined. Multiple regression analyses
      were used for statistical analysis. RESULTS: The type of sealing materials and
      the modified applications were significantly associated with microleakage
      (P<0.001). The significant impacts on penetration ability were the fissure type,
      material and mode of application (P<0.004). CLINICAL SIGNIFICANCE: Concise showed
      significantly better performance than Tetric Flow. The non-invasive cleaning
      method with an air polishing system and the use of drying agent improved the
      quality of sealants. The greatest influence on penetration ability was the
      fissure type.

PMID- 15151344
TI  - Eight ways to relieve practice stress.
AB  - Stress is a constant problem in dental practices because many dentists and dental
      team members do not understand what factors cause stress, let alone how to take
      away those stress-causing factors. Relieving stress in the eight areas of the
      practice discussed above is a proven and effective way for a dental practice to
      run more efficiently and ultimately, more profitably.

PMID- 15151345
TI  - Alcohol consumption and problems among road rage victims and perpetrators.
AB  - OBJECTIVE: Road rage has generated public concern; however, data on the causes of
      this behavior have not been available. We examine the alcohol consumption
      correlates of road rage victimization and perpetration based on a population
      survey of adults. METHOD: Data are based on the 2001-2002 Centre for Addiction
      and Mental Health Monitor, a repeated cross-sectional telephone survey of Ontario
      adults aged 18 and older (N = 2,610). Logistic regression analyses were performed
      with drinking measures (Alcohol Use Disorders Identification Test [AUDIT]
      consumption, dependence and problems) and demographic factors as independent
      variables. RESULTS: In the past year, 44.4% of respondents reported that someone
      shouted, cursed or made rude gestures at them, 6.0% were threatened with damage
      to their vehicle or personal injury, and 5.2% had someone attempt to or actually
      damage their vehicle or hurt them. Over the same period, 32% admitted shouting,
      etc., at someone, 1.7% threatened someone, and 1.0% attempted to or actually did
      damage someone's vehicle or hurt someone. Univariate analyses revealed several
      significant relationships between road rage and alcohol measures. Multivariate
      analyses revealed that the AUDIT alcohol problems measure was most consistently
      associated with measures of road rage victimization and perpetration, including
      reporting attempting or actually hurting someone or attempting or actually
      damaging his or her vehicle. CONCLUSIONS: These data indicate there is a
      significant relationship between alcohol problems, as measured by the AUDIT, and
      road victimization and perpetration. Further work must be undertaken to identify
      the mechanisms involved.

PMID- 15151346
TI  - A longitudinal study of the relationship between depressive symptoms and alcohol
      use in a sample of inner-city black youth.
AB  - OBJECTIVE: The purpose of this study was to examine longitudinally the
      relationship between depressive symptoms and alcohol use in a sample of black
      youth. METHOD: Participants were 458 black males and females interviewed annually
      during the high school years and then for 3 years during the transition to
      adulthood. The relationship was examined using growth curves with Hierarchical
      Linear Modeling. RESULTS: The results suggest that depressive symptoms decrease
      over time, whereas the use of alcohol increases. The findings also suggest that
      youths use alcohol as a way to cope with depressive symptoms and that males are
      more likely to use alcohol as self-medication. The results also indicate that
      changes in alcohol use do not predict depressive symptoms, but that life changes
      associated with the transition to adulthood, such as attending college, predict
      changes in depressive symptoms and alcohol use. CONCLUSIONS: Findings highlight
      the role of depressive symptoms for predicting alcohol use among black youth and
      the role of significant life transitions in altering the pattern of alcohol use
      presented previously by these youths.

PMID- 15151347
TI  - Serious health consequences associated with alcohol use among college students:
      demographic and clinical characteristics of patients seen in an emergency
      department.
AB  - OBJECTIVE: Heavy episodic alcohol use has been associated with numerous
      consequences among college students. However, neither the incidence nor the
      demographic and clinical characteristics of serious health consequences have been
      clearly defined in this population. This study is conducted to better understand
      clinical outcomes associated with alcohol use in college students. METHOD: In a
      prospective observational study, medical records of students presenting to a
      large university medical center emergency department were examined. Demographic
      and clinical features of alcohol-related visits were gathered on patients who
      were enrolled as undergraduates at a 4-year public institution during 2 academic
      years from July 2000 through June 2002. Enrollment was approximately 12,500
      undergraduates per year. RESULTS: Of all emergency visits, 13% were alcohol
      related; and of all undergraduate students, 0.7% presented with alcohol-related
      medical conditions each year. Injuries accounted for 53% of all visits, and acute
      intoxication accounted for 34%. Nine of 185 patients were hospitalized. Men aged
      21 years and older had the highest odds of visiting the emergency department.
      Trauma occurred more frequently among men, students > 18 years of age and white
      students. Accidents (84%) and fights (16%) were the sources of injuries. Acute
      intoxication occurred more frequently among women, students < or = 18 years of
      age and nonwhite students. CONCLUSIONS: Alcohol use contributes to a small yet
      significant proportion of emergency room visits for college students. Distinctive
      subgroups of college students, including legal-age drinkers, experience patterns
      of serious health consequences as a result of problem use of alcohol.

PMID- 15151348
TI  - Alcohol consumption predicts hypertension but not diabetes.
AB  - OBJECTIVE: This study examines the associations between alcohol consumption, Type
      2 diabetes and hypertension in a native American population. METHOD: Data were
      collected in a population-based cross-sectional and prospective study conducted
      on 3,789 individuals aged > or = 20 years. Reported alcohol consumption was
      classified as never, occasional or < 1 a day, 1-2 drinks a day, > or = 3 drinks a
      day, and occasional heavy drinking. The prevalence and incidence of diabetes and
      hypertension by categories of alcohol intake were determined. RESULTS: About 68%
      of men and 39% of women reported some degree of alcohol consumption. There was no
      association between alcohol consumption and prevalence or incidence of diabetes,
      but a positive, statistically significant association between blood pressure and
      alcohol consumption was found in both genders. After adjustment for age, body
      mass index (BMI) and diabetes in a proportional hazards model in men, moderate
      drinkers (occasional or < 1 drink a day and 1-2 drinks a day combined) had 1.24
      (95% confidence interval: 0.98-1.57) and occasional heavy drinkers had 1.49 (1.02
      2.17) times the incidence of hypertension as nondrinkers. The corresponding
      estimates of hypertension incidence for women were 1.53 (1.29-1.83) for moderate
      drinking and 1.38 (0.81-2.36) for occasional heavy drinking. As only 1% of
      participants reported > or = 3 drinks a day, this group was excluded from these
      analyses. CONCLUSIONS: Alcohol consumption did not affect the development of Type
      2 diabetes, but it was associated with increased risk of hypertension, and this
      effect was independent of diabetes or BMI in both genders.

PMID- 15151349
TI  - Engaging general practitioners in the management of hazardous and harmful alcohol
      consumption: results of a meta-analysis.
AB  - OBJECTIVE: A systematic review was undertaken of studies that test the
      effectiveness of different strategies used to increase general practitioners'
      rates of screening for and giving advice about hazardous and harmful alcohol
      consumption. METHOD: Resources were MEDLINE, EMBASE, Cinahl and the Cochrane
      Library (1966-2001). Inclusion criteria were those of the Effective Practice and
      Organisation of Care Group of the Cochrane Collaboration. A meta-analysis was
      undertaken, using a random effects model, of 15 programs identified in 12 trials.
      Effect sizes, calculated using the logged odds ratio, were adjusted by inverse
      variance weights to control for the sample sizes of the studies. RESULTS:
      Analysis of the intervention groups resulted in screening and advice-giving rates
      of 45% (95% CI: 33%-56%) and analysis of the comparison groups resulted in rates
      of 32% (95% CI: 20%-43%). The weighted mean effect size (logged odds ratio =
      0.73; 95% CI: 0.56-0.90) was heterogeneous. Regression analysis to explain the
      heterogeneity found a significant effect for alcohol-specific programs compared
      with general prevention programs in which alcohol was included, and for
      multicomponent programs compared with single component programs. No significant
      differences were found between educational-based or office-based interventions.
      CONCLUSIONS: Although the small numbers of programs studied suggest caution be
      used in interpreting the results, it seems it is possible to increase the
      engagement of general practitioners in screening and giving advice for hazardous
      and harmful alcohol consumption. Although considerably more research of high
      quality is needed, promising programs are those that have a specific focus on
      alcohol and those that are multicomponent.

PMID- 15151350
TI  - A comparison of personalized feedback for college student drinkers delivered with
      and without a motivational interview.
AB  - OBJECTIVE: This study evaluated the relative efficacy of personalized drinking
      feedback (PDF) delivered with and without a motivational interview (MI) for
      college student drinkers. METHOD: Heavy-drinking college students (N = 54; 691%
      female) were identified from a large screening sample and randomly assigned
      either to receive PDF during a single MI session or to receive PDF without an MI.
      Of these participants, 51 (94%) completed a 6-month follow-up assessment that
      included measures of alcohol consumption and alcohol-related problems. RESULTS:
      At 6-months postintervention, participants in both groups showed significant,
      small to moderate reductions in alcohol consumption, but the groups did not
      differ. Women showed larger reductions than men. Rates of alcohol-related
      problems remained relatively unchanged. CONCLUSIONS: The hypothesis that an MI
      would enhance the efficacy of PDF was not supported.

PMID- 15151352
TI  - Associations between adolescent drinking and driving involvement and self
      reported risk and protective factors in students in public schools in Washington
      State.
AB  - OBJECTIVE: This study examines associations between self-reported drinking and
      driving or being a passenger of a drinking driver and risk and protective factors
      in a general population of adolescents. METHOD: We used a two-staged sampling
      procedure to survey 2,955 students in Washington State public schools in Grades 9
      12. Students were asked if they were a passenger of, or had been, a drinking
      driver in the previous month. They were also asked about individual, parent,
      school and community risk and protective factors. Comparisons were made using
      hierarchical polychotomous logistic regression, entering age and gender and
      parent, school and community protective factors at the first step and individual
      risk factors at the second step. RESULTS: Driving after drinking in the previous
      month was reported by 12.1% of respondents and riding with a drinking driver was
      reported by an additional 17.6% of respondents. At the first step, driving after
      drinking was more likely and riding with a drinking driver was less likely among
      youth who were age 16 or older, and male students were more likely than female
      students to report driving after drinking. Parent, school and community support
      were each significantly associated with less driving after drinking, and school
      support was significantly associated with less riding with drinking drivers. At
      the second step, higher quantity and frequency of drinking, more smoking
      cigarettes and drug use and less seat belt use were each associated with both
      drinking and driving and riding with drinking drivers. Gun carrying was also
      associated with driving after drinking. CONCLUSIONS: Drinking and driving
      behaviors were associated with risk and protective factors in the community,
      school, family and individual. Pilot prevention programs should test the
      effectiveness of reducing drinking and driving involvement by addressing such
      factors.

PMID- 15151351
TI  - Adolescent heavy episodic drinking trajectories and health in young adulthood.
AB  - OBJECTIVE: This study examined the association of trajectories of heavy episodic
      drinking (at least five alcoholic drinks on one occasion) during adolescence with
      health status and practices at age 24. METHOD: Semiparametric group-based
      modeling and logistic regressions were used to analyze data from a longitudinal
      panel of 808 youths interviewed between 10 and 24 years of age. RESULTS: Four
      distinct trajectories of adolescent heavy episodic drinking were identified:
      nonheavy drinkers, late onsetters, escalators and chronic heavy drinkers.
      Overall, young adults who did not engage in heavy episodic drinking during
      adolescence had the lowest occurrence of health problems and were most likely to
      engage in safe health behaviors at age 24. Chronic and late-onset heavy episodic
      drinking during adolescence had negative effects on health status and practices
      at age 24. Adolescent chronic heavy drinkers were more likely to be overweight or
      obese and to have high blood pressure at age 24 than those who did not drink
      heavily in adolescence. Late-onset heavy drinkers were less likely to engage in
      safe driving practices at age 24 and were more likely to have been ill in the
      past year than adolescents who did not drink heavily. These health disparities
      remained even after current frequency of heavy episodic drinking at age 24, other
      adolescent drug use, ethnicity, gender and family poverty were controlled.
      CONCLUSIONS: Heavy episodic alcohol use during adolescence has long-term,
      negative health consequences. Distinct patterns of adolescent heavy drinking
      affect health status and practices in young adulthood differently.

PMID- 15151353
TI  - Adolescent alcohol reduction and cessation expectancies.
AB  - OBJECTIVE: Although many youths reduce or stop drinking without formal treatment,
      little is known of cognitive mechanisms influencing such alcohol change efforts
      during adolescence. The present research examines alcohol cessation expectancies
      of adolescents in the context of a cognitive-behavioral de-escalation model of
      alcohol use. Grounded in Developmental Social Information Processing theory (Coie
      and Dodge, 1998) and empirical findings on adolescent self-change process,
      alcohol cessation expectancies are defined as anticipated consequences of ceasing
      or decreasing drinking. The present study is the first to develop a measure of
      adolescent alcohol cessation expectancies. METHOD: A 23-item measure was
      administered to 5,446 high school students (51% female) as part of a survey on
      alcohol and drug use. RESULTS: Using data for adolescents who reported any
      history of alcohol use (N = 3,098), exploratory and confirmatory factor analyses
      identified expectations of global changes and social effects. Expectancy factor
      structure was examined within drinking groups (light, moderate, heavy drinkers)
      and as a function of age and change goal (reduction and cessation). Predictive
      validity of the expectancy measure was examined for youth who reported efforts to
      decrease or stop drinking during the prior year. Our results suggest greater
      differentiation in cessation expectancies with increased alcohol experience. The
      findings also provide evidence that youth cessation expectancies uniquely predict
      alcohol change efforts over and above alcohol use and problems. CONCLUSIONS:
      Youths maintain several types of alcohol reduction/cessation expectancies
      predictive of behavioral change efforts. Articulation of this construct for youth
      contributes to an understanding of mechanisms involved in adolescent efforts to
      reduce or stop drinking.

PMID- 15151355
TI  - Drinking patterns of older Americans: National Health Interview Surveys, 1997
      2001.
AB  - OBJECTIVE: The objective of this study was to estimate the quantity and frequency
      of alcohol consumption among current drinking Americans age 60 years and older,
      by gender and age. METHOD: Five years (1997-2001) of cross-sectional National
      Health Interview Survey data were pooled. Quantity (number of drinks consumed, on
      average, on drinking days), frequency (number of drinking days per year) and a
      composite quantity-frequency measure (average number of drinks per day) were
      defined. Age trends (between age 60 and 84 years) were tested using logistic
      regression. Analyses were weighted to produce national estimates. RESULTS: Among
      40,556 adults age 60 years and older, 52.8% (n = 8,136) of men and 37.2% (n =
      8,710) of women were current drinkers. Over increasingly older age groups of
      current drinking men and women (1) proportions consuming higher quantities of
      alcohol (two drinks or more) decreased (p trend < .001), whereas proportions
      consuming lower quantities (one drink) increased (p trend < .001); and (2)
      proportions drinking least frequently (< 12 days per year) and most frequently
      (260-365 days per year) increased (p trend < .05), whereas proportions drinking
      at intermediate frequencies remained stable or decreased. Differences in patterns
      for quantity alone and frequency alone were obscured by the composite quantity
      frequency measure. CONCLUSIONS: In a nationally representative survey, quantity
      and frequency of alcohol consumption showed strikingly different patterns of
      cross-sectional age-related change. In epidemiologic studies, quantity and
      frequency have been differentially associated with medical conditions prevalent
      in older populations. Investigators studying alcohol consumption in older people
      should consider reporting results separately by quantity and frequency.

PMID- 15151354
TI  - Effects of the menstrual cycle of white women on ethanol toxicokinetics.
AB  - OBJECTIVE: The aim of this study was to investigate the existing variations of
      the kinetics of ethanol in white women during the menstrual and luteal phases to
      further current understanding of the role of the menstrual cycle in gender
      differences in ethanol's adverse effects. METHOD: In a within-subjects design, 10
      female white volunteers were administered a moderate dose of ethanol (0.3 g/kg)
      in the morning after an overnight fast. On each test day, blood samples were
      collected before ethanol administration so that hormonal (estrogen, progesterone,
      luteinizing hormone and follicle stimulating hormone) and biochemical (hepatic
      and renal functions) analyses could be performed. Blood samples were also drawn
      from each volunteer to determine BAC and to examine toxicokinetic differences
      between the two phases using classical and Widmark's measures. RESULTS: The
      analysis of time-to-peak BAC in the two menstrual phases shows that there was no
      significant statistical difference when each phase was evaluated and in the
      interaction of the phase with time. The estimated toxicokinetic parameters did
      not show significant differences when the two phases were compared. CONCLUSIONS:
      Despite careful experimental design, which considered present debate and
      discussion in the literature, no significant differences between the two phases
      studied (menstrual and luteal) were observed.

PMID- 15151356
TI  - The relationship between health-related quality of life and two measures of
      alcohol consumption.
AB  - OBJECTIVE: The purpose of this study was to compare two measures of alcohol
      consumption and their relationship with health-related quality of life and to
      determine whether the health status of former drinkers differs from that of
      abstainers. METHOD: The study was carried out within the framework of a general
      population survey (4,472 persons aged 16-69 years) in two large Dutch cities. The
      Short Form-36 Health Survey (SF-36) was used as a measure of health-related
      quality of life. Measures of alcohol consumption compared were the Quantity
      Frequency-Variability (QFV) method, which measures the usual frequency and number
      of units of alcohol during weekdays and the weekend, and the Weekly drinking
      Recall (WR), which measures alcohol consumption during the week prior to
      completion of the WR questionnaire. RESULTS: A curvilinear relationship (inverse
      J shaped) was found between both measures of alcohol consumption and the
      subscales of the SF-36, except in the case of role problems-physical. For
      example, the 95% confidence interval of the odds ratios for former, light, heavy
      and excessive drinkers (using the QFV, with abstainers as reference group) versus
      the SF-36 subscale general health are, respectively, 0.55-1.39, 0.43-0.74, 0.31
      0.68 and 0.38-0.99. Former drinkers have an intermediate position between
      drinkers and abstainers on the SF-36 subscales, except in role problems-physical
      (poorer health than abstainers) and mental health (better health than
      abstainers). CONCLUSIONS: Both measures of alcohol consumption have a similar
      relationship with the subscales of the SF-36. The fact that former drinkers show
      a difference on two subscales (more role problems-physical but better mental
      health) indicates that this category may have a complex, or at least a different,
      relationship with aspects of health compared with abstainers and drinkers.

PMID- 15151357
TI  - The role of drinking restraint in alcohol dependence: validation of the
      temptation and restraint inventory in an alcohol dependent sample.
AB  - OBJECTIVE: The Temptation and Restraint Inventory (TRI) is commonly used to
      measure drinking restraint in relation to problem drinking behavior. However, as
      yet the TRI has not been validated in a clinical group with alcohol dependence.
      METHOD: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed
      alcohol dependence completed the TRI and measures of problem drinking severity,
      including the Alcohol Dependence Scale and the quantity, frequency and week total
      of alcohol consumed. RESULTS: The factor structure of the TRI was replicated in
      the alcohol dependent sample. Cognitive Emotional Pre-occupation (CEP), one of
      the two higher order factors of the TRI, demonstrated sound predictive power
      toward all dependence severity indices. The other higher order factor, Cognitive
      Behavioral Control (CBC), was related to frequency of drinking. There was limited
      support for the CEP/CBC interactional model of drinking restraint. CONCLUSIONS:
      Although the construct validity of the TRI was sound, the measure appears more
      useful in understanding the development, maintenance and severity of alcohol
      related problems in nondependent drinkers. The TRI may show promise in detecting
      either continuous drinking or heavy episodic type dependent drinkers.

PMID- 15151358
TI  - Does marital status predict long-term drinking? Five-year observations of
      dependent and problem drinkers.
AB  - OBJECTIVE: Married individuals have lower rates of problem drinking, but little
      is known about this relationship in the context of other factors. This
      longitudinal analysis examines marital status with other individual predisposing,
      problem severity and social predisposing characteristics to understand its
      strength in predicting alcohol consumption over 5 years. METHOD: A probability
      sample of dependent (n = 600) and problem (n = 992) drinkers was recruited
      through consecutive adult intakes from a Northern California county's alcohol and
      drug treatment programs and through a general population survey. Annual volume of
      drinks consumed over a 5-year period-measured at baseline, and at 1, 3 and 5
      years later-was estimated in four nested models using maximum likelihood
      estimation via PROC MIXED. RESULTS: In simpler models that examined only marital
      status, married individuals drank significantly less than those never married (p
      < .01 for problem drinkers and p < .05 for dependent drinkers); however, when our
      models added individual predisposing, problem severity and social predisposing
      characteristics, marital status was no longer significant in predicting a
      trajectory of decreased drinking. For problem drinkers, the following
      characteristics were more important than marital status in predicting alcohol
      consumption over the 5 years: individual predisposing characteristics (age, p <
      .001; income, p < .001; education, p < .001; and age of initiation of regular
      alcohol use, p < .001), problem severity (number of alcohol dependence symptoms,
      p < .001; number of alcohol-related social consequences, p < .001; and higher
      drug severity, p < .05) and social predisposing characteristics (family member
      with an alcohol problem, p < .05; the size of heavy alcohol- and drug-using
      social network, p < .05; and chemical dependency treatment in the prior year, p <
      .001). For those who were alcohol dependent, income (p < .05), number of alcohol
      dependence symptoms (p < .001), higher drug severity (p < .05) and a heavy
      alcohol- and drug-using social network (p < .05 ) were more important than
      marital status in predicting consumption. CONCLUSIONS: In longitudinal models,
      individual predisposing, problem severity and social predisposing characteristics
      are more important than marital status in predicting alcohol consumption.

PMID- 15151359
TI  - Decreased taxation, spirits consumption and alcohol-related problems in
      Switzerland.
AB  - OBJECTIVE: The spirits market in Switzerland was reformed in 1999 in accordance
      with the World Trade Organization agreement. The resulting tax reform and
      increased competition have resulted in markedly reduced prices for foreign
      spirits, and a previous study showed that spirits consumption increased
      significantly after the tax reform. The present study examined whether alcohol
      related problems also increased at follow-up and if they did, whether the
      increase was the result of increased spirits consumption. Further correlates of
      alcohol-related problems were also explored. METHOD: Data were obtained from a
      longitudinal study on changes in alcohol consumption in Switzerland. The baseline
      survey was conducted 3 months before the tax reform, and the follow-up was
      conducted 28 months after the tax reform. A randomly selected sample of 4,007
      residents aged 15 years or older participated in the baseline survey, and 73% of
      this sample participated in the follow-up survey. Alcohol consumption was
      measured on the basis of a graduated frequency, and alcohol-related problems were
      measured by items taken from the Alcohol Use Disorder Identification Test
      (AUDIT). RESULTS: Findings indicate that alcohol-related problems increased
      significantly at follow-up. The significance disappeared, however, after
      controlling for spirits consumption, indicating that the increase of alcohol
      related problems at follow-up was mainly mediated through increased consumption
      of spirits. The multiple regression models showed that spirits, beer and wine
      consumption, gender, Age*Spirits Consumption interaction, region, smoking status,
      heavy-drinking frequency and average number of drinks were significant correlates
      of alcohol-related problems. CONCLUSIONS: Alcohol-related problems increased at
      the follow-up, particularly among younger age groups who consumed more spirits.
      Prevention programs on alcohol-related problems should target young people.

PMID- 15151360
TI  - Intensity of acute services, self-help attendance and one-year outcomes among
      dual diagnosis patients.
AB  - OBJECTIVE: This study of dual diagnosis patients examined the associations of the
      intensity of acute care services and 12-step self-help group attendance with
      substance use and mental health outcomes. METHOD: Participants (n = 230; 96% men)
      received treatment in one of 14 residential programs and were evaluated with the
      Addiction Severity Index at discharge (98%) and at 1-year follow-up (80%).
      RESULTS: High service intensity in acute treatment was associated with better
      substance use and family/social outcomes both at discharge and at 1 year when
      patients' intake status was controlled. More attendance at 12-step self-help
      groups was also associated with better patient substance use and psychiatric
      outcomes, both during and following treatment. The benefits of more 12-step group
      attendance, however, depended on whether acute treatment was of low or high
      service intensity. More 12-step group attendance during treatment was associated
      with better alcohol and drug outcomes at discharge only among patients treated in
      low-service-intensity programs; and more attendance postdischarge was associated
      with better psychiatric and family/social functioning at 1 year only among
      patients receiving low-service-intensity care. CONCLUSIONS: We suggest potential
      means by which high-service-intensity acute care programs might better facilitate
      patients' postdischarge use of 12-step self-help groups to benefit outcomes.

PMID- 15151361
TI  - Thoughts on the pathogenesis of type 1 diabetes and on the arrest of autoimmune
      beta-cell destruction by peptide p277 vaccination.

PMID- 15151362
TI  - Pancreatic transcription factors: implications for diabetes therapy.
AB  - Since both major forms of diabetes involve inadequate function of pancreatic beta
      cells, intensive research is ongoing to better understand how beta cells perform
      their complex role of secreting the hormone insulin in response to physiologic
      needs. Identification and characterization of pancreatic transcription factors
      has revealed that they play a crucial role not only in maintenance of mature beta
      cell function but also at multiple stages in pancreatic development. Furthermore,
      recent reports have revealed their potential to convert non-beta cells into
      insulin-producing cells, which in some cases can function to ameliorate diabetes
      in experimental animals. The ability to translate these successes to the clinic
      will require a detailed mechanistic understanding of the molecular basis of
      action of these proteins. Specific gene regulation in beta cells involves the
      action of multiple transcription factors recruited to the promoter and
      functioning synergistically to activate transcription, in part through
      recruitment of co-activator proteins and components of the basal transcriptional
      machinery. In addition, the process involves modification of chromatin structure,
      the details of which are beginning to be elucidated. Our ability to modulate gene
      expression patterns may lead to developing ways to provide an unlimited supply of
      functional beta cells for transplantation, permitting a dramatic improvement in
      therapeutic options for diabetes.

PMID- 15151363
TI  - Generation of insulin-producing cells from stem cells for cell replacement
      therapy of type 1 diabetes.
AB  - Type 1 diabetes mellitus is caused by an autoimmune destruction of pancreatic
      islet beta cells, leading to insulin deficiency. Beta-cell replacement is
      considered the optimal treatment for type 1 diabetes, however it is severely
      limited by the shortage of human organ donors. An effective cell-replacement
      strategy depends on the development of an abundant supply of beta cells and their
      protection from recurring immune destruction. Stem/progenitor cells, which can be
      expanded in tissue culture and induced to differentiate into multiple cell types,
      represent an attractive source for generation of cells with beta-cell properties:
      insulin biosynthesis, storage, and regulated secretion in response to physiologic
      signals. Embryonic stem cells have been shown to spontaneously differentiate into
      insulin-producing cells at a low frequency, and this capacity could be further
      enhanced by tissue culture conditions, soluble agents, and expression of dominant
      transcription factor genes. Progenitor cells from fetal and adult tissues, such
      as liver and bone marrow, have also been shown capable of differentiation towards
      the beta-cell phenotype in vivo, or following expression of dominant
      transcription factors in vitro. These approaches offer novel ways for generation
      of cells for transplantation into patients with type 1 diabetes.

PMID- 15151364
TI  - Gestational diabetes mellitus: what else is new?

PMID- 15151365
TI  - Why pumps? Continuous subcutaneous insulin infusion for children and adolescents
      with type 1 diabetes.
AB  - CSII is a feasible, safe and well-accepted mode of therapy for many children with
      type 1 diabetes. For a significant number of patients and parents, it serves as a
      much easier means of coping with the huge daily burden of diabetes. Therefore, we
      believe that both CSII and MDI should be made available to the diabetic team and
      the patients to better tailor therapy, improve satisfaction and decrease the fear
      of hypoglycemia.

PMID- 15151366
TI  - Atypical antipsychotics and diabetes mellitus: an association.
AB  - The use of atypical antipsychotic agents is associated with the induction of both
      an indolent progression to insulin-resistant diabetes and an idiosyncratic beta
      cell toxicity presenting as diabetic ketoacidosis, both of which are usually
      reversible or improved subsequent to cessation of treatment. The underlying
      mechanisms are unclear at present. Nonetheless, in light of the now numerous
      reports on the adverse metabolic effects of these drugs, the Consensus
      Development Conference which met in November 2003 recommends that metabolic risks
      be considered when starting atypical antipsychotic drugs. Their operative
      checklist includes baseline screening of candidates for antipsychotic treatment,
      which includes personal/family history of diabetes, weight, waist circumference,
      blood pressure, fasting plasma glucose and fasting lipid profile, and then follow
      up of these parameters. Furthermore, the health professionals, patients, family
      and caregivers should be aware of the signs and symptoms of diabetes, especially
      when acute decompensation occurs which is commensurate with diabetic
      ketoacidosis. We wish, through this short report, to raise the awareness of
      physicians treating psychiatric patients to the possibility of new-onset diabetes
      during therapy with atypical antipsychotic drugs and to emphasize the necessity
      for increased vigilance and close metabolic follow-up of these patients.
      Moreover, the choice of the best antipsychotic treatment for each patient should
      take into consideration the diabetogenic effect of the different treatment
      options as well the other side effects.

PMID- 15151367
TI  - The diabetic Charcot foot.

PMID- 15151369
TI  - Diabetic skin complications: a need for reorganizing the categories of diabetes
      associated complications.

PMID- 15151368
TI  - Insulin pump therapy for 1-6 year old children with type 1 diabetes.
AB  - BACKGROUND: The management of diabetes in preschool children poses unique
      difficulties for both the families and the medical team. OBJECTIVE: To test the
      feasibility and safety of insulin pump therapy in the 1-6 year age group in order
      to improve quality of life and metabolic control. METHODS: The study group
      comprised 15 type 1 diabetic children aged 1-6 years old (mean +/- SD, 3.8 +/-
      1.2 years) from three diabetes centers. Insulin pump therapy was applied for 12
      months. Data, including insulin dose, hemoglobin A1c, hypoglycemic events, as
      well as scores on the Diabetes Quality of Life Measure Questionnaire and the
      Diabetes Treatment Satisfaction Questionnaire, were collected and compared with
      the multiple daily injection treatment prior to entry into the study, RESULTS:
      HbA1c was measured at the beginning of the study and at 2, 4, 8 and 12 months
      later; the respective levels (mean +/- SD) were 8.82 +/- 0.98, 8.45 +/- 1.05,
      8.37 +/- 0.85, 8.32 +/- 0.71, 8.18 +/- 0.90%. HbA1c measurements after 12 months
      were significantly lower than at the beginning of the study (P < 0.05). There
      were no significant differences in insulin dose and the total number of
      hypoglycemic events. In both the DQOL and DTSQ scales there were significant
      differences in scores in favor of the insulin pump period (43.7 +/- 8.0 versus
      33.7 +/- 7.9, P < 0.001; and 10.9 +/- 2.3 versus 14.5 +/- 2.3, P < 0.001),
      respectively. CONCLUSIONS: For very young diabetic children, insulin pump therapy
      improves quality of life and is feasible and safe. It should be considered as an
      optional mode of therapy for this age group.

PMID- 15151370
TI  - Permanent neonatal diabetes.

PMID- 15151371
TI  - Initiating insulin in type 2 diabetes mellitus: the earlier the better.

PMID- 15151372
TI  - Initiating insulin in type 2 diabetes mellitus: there's no rush.

PMID- 15151373
TI  - Angiotensin receptor blockers do not have an advantage over angiotensin
      converting inhibitors [corrected].

PMID- 15151374
TI  - Angiotensin receptors blockers are preferred to angiotensin-converting inhibitors
      [corrected].

PMID- 15151376
TI  - Primary prevention of type 2 diabetes: how do we do it?

PMID- 15151375
TI  - Prevention of type 1A diabetes: update.

PMID- 15151377
TI  - Haptoglobin: a major susceptibility gene for diabetic cardiovascular disease.

PMID- 15151378
TI  - 5-Lipoxygenase activating protein (ALOX5AP): association with cardiovascular
      infarction and stroke.

PMID- 15151379
TI  - Greater and greater pressures on natural resources as world food consumption
      grows and demands increase.

PMID- 15151380
TI  - Satellite change detection analysis of deforestation rates and patterns along the
      Colombia-Ecuador border.
AB  - This study uses Landsat satellite data to document the rates and patterns of land
      cover change along a portion of the Colombia-Ecuador border during a 23-yr period
      (1973-1996). Human colonization has resulted in extensive deforestation in both
      countries. Satellite change detection analysis showed that the annual rates of
      deforestation were considerably higher for the Colombian side of the border. In
      addition, loss of forest cover on the Colombian side for the study period was
      almost 43%, while only 22% on the Ecuadorian side. The study found that there is
      no single factor driving deforestation on either side of the border, but
      concluded that the higher rates on the Colombian side may be due to higher
      colonization pressures and intensification of illegal coca cultivation. On the
      Ecuador side of the border the satellite images documented patterns of
      deforestation that reflected road networks associated with oil exploration and
      development.

PMID- 15151381
TI  - Controlling lead concentrations in human blood by regulating the use of lead in
      gasoline.
AB  - After having been emitted at maximum rates in the 1960s and 1970s, lead has
      become less ubiquitous in industrialized countries as a result of increasingly
      stringent policies to limit the use of this heavy metal as an anti-knock additive
      in gasoline. Using a detailed reconstruction of lead emissions in Europe (PbE),
      of the air concentration of lead in Europe (PbC) and repeated measurements of
      lead concentrations in human blood (PbB) in Germany since about 1980, we have
      constructed an empirical model that estimates PbB given PbE. This model is used
      for 2 purposes: i)To estimate PbB levels for the 1960s and 1970s in Germany, when
      emissions were maximum and monitoring blood levels had not yet begun. It turns
      out that PbB peak emissions were reaching a mean level, which health officials
      considered potentially harmful for fetuses and small children. ii) To estimate
      how PbB levels may have developed if regulations of the use of lead in gasoline
      had been implemented differently. In case of no or delayed regulations, the model
      estimates that PbB levels well beyond the critical level would have emerged.
      Thus, the regulation instituted in Germany since the 1970s has reduced
      significant health hazards.

PMID- 15151382
TI  - The tail feathers of osprey nestlings (Pandion haliaetus L.) as indicators of
      change in mercury load in the environment of southern Sweden (1969-1998): a case
      study with a note on the simultaneous intake of selenium.
AB  - The tail feathers of 104 osprey nestlings (Pandion haliaetus) from Lake Asnen,
      southern Sweden, were analyzed for total mercury and selenium content.
      Concentrations of mercury in feathers from the western part of the lake fell
      during the period 1969-1998, when pollution from industrial mercury had decreased
      and a paper mill upstream of the lake was closed down in 1979. Nestlings from the
      eastern part of the lake had initially lower levels of mercury, predominantly
      from atmospheric fallout. The levels did not decrease during the period. The
      reason for the differences seems to be the limited water flow between the western
      and the eastern part of the lake. The selenium concentrations were constant over
      time and approximately the same in both parts of the lake. The total-Hg/Se ratio
      in the western part of the lake was 2.94, which is somewhat higher than the 1:1
      molar ratio constant (2.54). This indicates that the bioaccumulated quantity of
      selenium which is thought to be protective for the organisms against the toxic
      effects of mercury, is somewhat insufficient to bind all body mercury.

PMID- 15151383
TI  - Heavy-metal pollution and arseniasis in Hetao region, China.
AB  - In the Hetao region in northern China drinking water has become toxic due to the
      presence of arsenic (As) and other heavy metals in soil and water. The 7 counties
      in this region cover approx. 6100 km2, and in all 180,000 people are suffering
      from the toxic effects of contaminated drinking water. However, very few studies
      have been carried out in the region on the possible source of this arsenic. This
      paper is based on studies of the distribution of heavy metals in soil and
      groundwater. Results show that the average content of As is 0.483 microg g(-1) in
      groundwater and 13.74 microg g(-1) in soil. These levels are higher than the
      drinking water standard of 0.05 microg g(-1) recommended by the World Health
      Organization in 1984, and for the local background level in soil (5.20 microg g(
      1)). This heavy-metal content in water and soil decreases gradually with
      increasing distance from the contaminated area, which fronts the Yin Mountains.
      The ratios of the Pb and Sr isotope contents in water are closely related to the
      ratios found in the water of the regions' mining area, and the ratios in soil
      correspond to the content of As in groundwater and soil in the area where
      pathological changes have been detected. Results suggest that the contaminants
      originate in the ore deposit zone fronting Yin mountains in the upper reaches of
      the Hetao Region.

PMID- 15151384
TI  - Flood-risk management strategies for an uncertain future: living with Rhine River
      floods in The Netherlands?
AB  - Social pressure on alluvial plains and deltas is large, both from an economic
      point of view and from a nature conservation point of view. Gradually, flood
      risks increase with economic development, because the expected damage increases,
      and with higher dikes, because the flooding depth increases. Global change,
      changing social desires, but also changing views, require a revision of flood
      risk management strategies for the long term. These should be based on resilience
      as opposed to the resistence strategy of heightening dikes. Resilience strategies
      for flood-risk management imply that the river is allowed to temporarily flood
      large areas, whereas the flood damage is minimized by adapting land use. Such
      strategies are thus based on risk management and 'living with floods' instead of
      on hazard control. For The Netherlands, one of the most densely populated deltas
      in the world, alternative resilience strategies have been elaborated and assessed
      for their hydraulic functioning and 'sustainability criteria'.

PMID- 15151385
TI  - Growth in otter (Lutra lutra) populations in the UK as shown by long-term
      monitoring.
AB  - European otters declined dramatically from the 1950s, disappearing from many
      rivers. We report here on longterm monitoring (from 1977) in 3 catchments in
      western Britain that were recolonized naturally and in 2 catchments in eastern
      England that were reinforced by captive-bred otters. A minimum of 16-years data
      was collected on each river until 2002. At a series of sites in each study river,
      the percentages which were positive for otters and the number of spraints per
      sprainting site were recorded and combined to produce an annual index of
      population. One western river, naturally recolonized, showed rapid early
      population growth for 5 years, followed by slower growth, while growth was
      steadier in 2 catchments which already held some otters at the beginning of the
      study. Colonization on the eastern rivers was slower, with greater fluctuations
      over time. Annual population growth rates were estimated at 1-7%, higher in the
      earlier years. A strategy for annual monitoring of otters is recommended.

PMID- 15151386
TI  - Baltic Sea hazardous substances management: results and challenges.
AB  - The introduction into the Baltic Sea of hazardous substances that are persistent,
      bioaccumulate, and are toxic is an important environmental and human health
      problem. Multilateral efforts to address this problem have primarily been taken
      under the Helsinki Commission (HELCOM). This article examines past HELCOM efforts
      on hazardous substances, and discusses future challenges regarding their
      management. The article finds that past actions on hazardous substances have had
      a positive effect on improving Baltic environmental quality and reducing human
      health risks, although there are remaining issues and difficulties that need to
      be addressed. In particular, four related future challenges for HELCOM management
      of hazardous substances are identified and discussed: i) the need to engender
      further implementation and building public and private sector capacities; ii) the
      need to improve data availability, quality and comparability across the region
      and international fora; iii) the need to strengthen existing regulations and
      incorporate new issues; and iv) the need to effectively coordinate HELCOM
      activities with efforts on hazardous substances in other international fora.

PMID- 15151387
TI  - Quantifying the global fractionation of polychlorinated biphenyls.
AB  - Due to the wide range of their physical-chemical properties, polychlorinated
      biphenyls (PCBs) have played an important role in the derivation of the global
      fractionation hypothesis, which predicts changes in the composition of persistent
      organic pollutant mixtures with latitude. Recent historical emission estimates,
      the derivation of an internally consistent property data set, in combination with
      a zonally averaged global fate and transport model, allow a quantitative
      investigation of the compositional shifts PCBs experience as a function of
      environmental compartment, latitude and time. Model simulations reproduce the
      higher relative abundance of lighter PCB congeners with increasing latitude,
      observed in air and soil, and quantify the relative importance of partitioning,
      persistence and emissions in establishing PCB patterns. Compositional variations
      consistent with global fractionation, as well as inverted concentration profiles
      with higher levels in the Arctic than at lower latitudes, are consistent with
      only minor fractions of the global PCB inventory being transferred northward.

PMID- 15151388
TI  - Sustainable management of alpine meadows on the Tibetan Plateau: problems
      overlooked and suggestions for change.

PMID- 15151389
TI  - Discovery of Sphaeroma terebrans, a wood-boring isopod, in the red mangrove,
      Rhizophora mangle, habitat of northern Florida Bay.

PMID- 15151390
TI  - Hopping of a single hole in hexakis[4-(1,1,2-triphenyl-ethenyl)phenyl]benzene
      cation radical through the hexaphenylbenzene propeller.
AB  - A versatile synthesis of a dendritic structure (5) is described in which six
      tetraphenylethylene moieties are connected to a central benzene ring in such a
      way that one of the phenyl rings of each tetraphenylethylene is also part of the
      propeller of the hexaphenylbenzene core. Observation of multiple oxidation waves
      in its cyclovoltammogram as well as an intense charge-resonance transition in the
      near-IR region in its cation radical spectrum suggests that a single hole
      delocalizes via electron transfer over six identical redox-active centers.
      [structure--see text]

PMID- 15151391
TI  - Redox behavior of ferrocene-containing rotaxane: transposition of the rotaxane
      wheel by redox reaction of a ferrocene moiety tethered at the end of the axle.
AB  - A rotaxane with a ferrocene moiety at the axle terminus was prepared. The redox
      potential of the ferrocene moiety decreased by ca. 80 mV when the rotaxane had a
      crown ether wheel capable of moving on the axle. Thus, the stabilization of the
      oxidized state of the ferrocene moiety is assumed to accompany the transposition
      of the wheel component on the axle toward the ferrocene moiety. [reaction--see
      text]

PMID- 15151392
TI  - Isolation and epimerization kinetics of the first diastereoisomer of an
      inherently chiral uranyl-salophen complex.
AB  - The first diastereoisomeric mixture of an inherently chiral uranyl-salophen
      complex was prepared using (S)-naproxen as a chiral derivatizing agent. Slow
      crystallization from diisopropyl ether-chloroform afforded one pure
      diastereoisomer in 45% yield. Kinetic studies allowed the determination of the
      epimerization rate. [reaction--see text]

PMID- 15151393
TI  - A blue-to-red energy-transfer thymidine analogue that functions in DNA.
AB  - The thymidine analogue 1 is a blue-to-red energy transfer cassette designed to
      absorb UV light in the 300 nm region and emit it as fluorescence at around 520
      nm. When incorporated into DNA, the fluorescence intensity of this modified
      nucleobase is not significantly reduced by the surrounding structure in the
      oligonucleotides. [structure--see text]

PMID- 15151395
TI  - Efficient synthesis of poly(phenylazomethine) dendrons allowing access to higher
      generation dendrimers.
AB  - We have developed a novel synthetic method of phenylazomethine dendrons that uses
      4,4'-methylenedianiline instead of 4,4'-diaminobenzophenone to synthesize the
      precursor of the phenylazomethine dendron and then oxidized the precursor to the
      next-generation dendron. For this method, the productivity of the dendrons has
      been significantly increased. Furthermore, as the synthesis of high-generation
      dendrons becomes easier, synthesis of DPA G5 was achieved. [structure--see text]

PMID- 15151394
TI  - Photochemical preparation of 1,3,5,7-tetracyanoadamantane and its conversion to
      1,3,5,7-tetrakis(aminomethyl)adamantane.
AB  - New adamantane derivatives 1 and 2 that bear functionalized one-carbon extensions
      at all four bridgehead positions have been prepared. Radical nucleophilic
      substitution (S(RN)1) reaction of 1,3,5,7-tetrabromoadamantane with cyanide
      produces 1,3,5,7-tetracyanoadamantane (1), which was reduced with borane reagents
      to 1,3,5,7-tetrakis(aminomethyl)adamantane (2). Improvements in the preparation
      of 1,3,5,7-tetrahaloadamantanes (halogen = Br, Cl, I) are also reported.
      [structure--see text]

PMID- 15151396
TI  - Synthesis of phakellistatin 13 and oxidation to phakellistatin 3 and
      isophakellistatin 3.
AB  - The natural product phakellistatin 13 cyclo-(TrpProPheGlyProThrLeu) was
      synthesized. Photosensitized oxidation of phakellistatin 13 gave the natural
      products phakellistatin 3 and isophakellistatin 3, demonstrating for the first
      time that a tryptophan residue can be directly converted to the corresponding 3a
      hydroxypyrrolo[2,3-b]indoline in a full length peptide. Competitive oxidation of
      the indoline product was identified as the cause of low mass balance and is
      probably the source of low mass balance in the oxidative cyclization of all
      tryptamine derivatives. [reaction--see text]

PMID- 15151397
TI  - Concerted nature of AB ring formation in the enzymatic cyclization of squalene to
      hopenes.
AB  - The cyclization of the A-B rings of squalene to hopene is studied computationally
      (DFT). A transition structure is found for a concerted, asynchronous pathway for
      the formation of chair-chair decalin carbocation. The computationally derived
      conformer leading to this asynchronous transition structure is remarkably similar
      to the analogous region of 2-azasqualene encapsulated by squalene-hopene cyclase
      recently reported by Schulz. A concerted A-B ring closure is likely to occur in
      the cyclization of squalene to hopene. [structure--see text]

PMID- 15151398
TI  - Lithium amide assisted asymmetric Mannich-type reactions of menthyl acetate with
      PMP-aldimines.
AB  - A lithium enolate of menthyl acetate added to PMP-imines, in the presence of an
      equimolar amount of lithium diisopropylamide, affords the Mannich-type addition
      products in high stereoselectivity. [reaction--see text]

PMID- 15151399
TI  - Selectivity enhancement in the Rh(II)-catalyzed cyclopropanation of styrene with
      (silanyloxyvinyl)diazoacetates.
AB  - The cyclopropanation of styrene with (silanyloxyvinyl)diazoacetates proceeds with
      exceptional diastereo- and enantioselectivity in the presence of chiral Rh(II)
      catalysts. 1,8-Naphthoyl-protected amino acids are the most effective Rh(II)
      ligands for these transformations. [reaction--see text]

PMID- 15151400
TI  - Linked photoswitches where both photochromes open and close.
AB  - In the dithienylethene photochrome series, linking two photochromes together
      directly, or with an ethynyl spacer, shuts down the photoswitching of one of the
      photochromes. We report here, that for dihydropyrenes, two photochromes can be
      linked together without affecting the ability of either to photoswitch. [reaction
      -see text]

PMID- 15151401
TI  - Instant ligand libraries. Parallel synthesis of monodentate phosphoramidites and
      in situ screening in asymmetric hydrogenation.
AB  - Chiral phosphoramidites have been identified as excellent ligands for various
      metal-catalyzed enantioselective transformations. Taking advantage of their easy
      preparation and modular nature, we designed a fully automated protocol for the
      parallel preparation of a library of 32 phosphoramidites and its screening in
      asymmetric hydrogenation of amino acid precursors. This initial study led to the
      discovery of a new ligand for the preparation of an enantiopure beta(3)
      homoalanine precursor. [structure--see text]

PMID- 15151402
TI  - Solution and X-ray structure of triethylsilylmethyl-substituted tropylium cation.
AB  - The beta-silyl tropylium cation 9 has been successfully generated in the presence
      of the noncoordinating counterion tetrakis(pentafluorophenyl)borate in benzene
      and toluene. The (13)C and (29)Si NMR spectra of 9 demonstrate that the beta
      silicon substituent interacts strongly with the aromatic pi-system of the cation
      by hyperconjugation. The crystal structure of 9 shows structural effects
      consistent with this interaction. [structure--see text]

PMID- 15151403
TI  - Highly diastereoselective indium-mediated allylation of chiral hydrazones.
AB  - The indium-mediated allylation of chiral hydrazones was investigated. Essentially
      complete diastereoselectivity and quantitative yields were obtained for
      substrates derived from both aromatic and aliphatic aldehydes. [reaction--see
      text]

PMID- 15151404
TI  - Pd-catalyzed carbonylative lactamization: a novel synthetic approach to FR900482.
AB  - An asymmetric synthesis of the benzazocine core of FR900482 has been achieved in
      15 steps from 3,5-dinitro-p-toluic acid. Key features of the synthesis include an
      enantioselective N-methylephedrine-mediated zinc acetylide addition to a highly
      enolizable arylacetaldehyde and a novel Pd-catalyzed carbonylative lactamization
      to form an eight-membered ring. [reaction--see text]

PMID- 15151405
TI  - Application of enantioselective radical reactions: synthesis of (+)-ricciocarpins
      A and B.
AB  - Enantioselective synthesis of (+)-ricciocarpins A and B has been achieved in 41
      and 45% overall yields, respectively, starting from a beta-substituted
      oxazolidinone. The key steps in the strategy are an enantioselective conjugate
      radical addition and the addition of a furyl organometallic to a key aldehyde
      intermediate. [reaction--see text]

PMID- 15151406
TI  - Synthesis of 4-fluorinated UDP-MurNAc pentapeptide as an inhibitor of bacterial
      growth.
AB  - 4-Fluorinated UDP-MurNAc pentapeptide, 2, has been synthesized. In our previous
      study, UDP-MurNAc pentapeptide analogue 1 was found to be incorporated into the
      bacterial cell wall through biosynthesis. Compound 2 showed growth-inhibition
      activity against Gram-positive bacteria when it was added to growth media at 0.01
      mg/mL. [structure--see text]

PMID- 15151407
TI  - A novel asymmetric vinylogous tin-Pummerer rearrangement.
AB  - A new type of vinylogous tin-Pummerer rearrangement reaction was observed when
      benzyl tin derivatives containing a sulfinyl group at the ortho position were
      allowed to react with acyl chlorides or TFAA. The reaction is thought to proceed
      by nucleophilic attack of the leaving carboxylate at the gamma-position of the
      conjugated thionium ion. The enantioselectivity (ee) of the reaction can reach
      values as high as 98%. The observed stereoselectivity is related to the nature of
      the solvent, the temperature employed, and the stability of the migrating
      carboxylate anion. [reaction--see text]

PMID- 15151409
TI  - Novel N1-C4 beta-lactam bond breakage. Synthesis of enantiopure alpha-alkoxy
      gamma-keto acid derivatives.
AB  - Addition reaction of 2-(trimethylsilyl)thiazole (TMST) to cis- or trans-4-formyl
      beta-lactams gave enantiopure alpha-alkoxy-gamma-keto acid derivatives via a
      novel N1-C4 bond breakage of the beta-lactam nucleus. This is the first time that
      the cleavage of the N1-C4 bond on the beta-lactam nucleus has been shown to occur
      in 2-azetidinones lacking an aryl moiety at C4. [reaction--see text]

PMID- 15151408
TI  - Highly effective synthetic methods for substituted 2-arylbenzofurans using [3,3]
      sigmatropic rearrangement: short syntheses of stemofuran a and eupomatenoid 6.
AB  - A new and efficient synthesis of 2-arylbenzofurans has been achieved via a route
      involving acylation and subsequent [3,3]-sigmatropic rearrangement of oxime
      ethers. Its synthetic utility is demonstrated by a short synthesis of stemofuran
      A and eupomatenoid 6 in which no procedure for protection of the phenolic
      hydroxyl groups is needed. [reaction--see text]

PMID- 15151410
TI  - Double C-H activation strategy for the asymmetric synthesis of C2-symmetric
      anilines.
AB  - Rh(2)(S-DOSP)(4)-catalyzed C-H activation to N,N-dimethylanilines is described. A
      double C-H activation was possible by using an excess of methyl aryldiazoacetate,
      and this provided a very direct approach to C(2)-symmetric anilines. [reaction-
      see text]

PMID- 15151411
TI  - A concise and stereoselective synthesis of the A-ring fragment of the gambieric
      acids.
AB  - The A-ring fragment of the gambieric acids has been prepared by a short and
      efficient route. The key 3(2H)-furanone intermediate has been obtained by [2,3]
      rearrangement of an allylic oxonium ylide generated from intramolecular reaction
      of a crotyl ether with a copper carbenoid. A single stereogenic center has been
      set by using a chiral pool starting material and the other three have been
      established by using highly diastereoselective substrate-controlled
      transformations. [reaction--see text]

PMID- 15151412
TI  - Efficient methodology for the synthesis of 2-C-branched glyco-amino acids by ring
      opening of 1,2-cyclopropanecarboxylated sugars.
AB  - An efficient methodology for the synthesis of 2-C-branched glyco-amino acid
      derivatives by diastereoselective ring opening of 1,2-cyclopropanecarboxylated
      sugars in good yields is reported. [reaction--see text]

PMID- 15151413
TI  - Fukui function as a descriptor of the imidazolium protonated cation resonance
      hybrid structure.
AB  - The Lewis structures that contribute to the imidazolium protonated cation
      resonance hybrid can be explained in a unified way in terms of the Fukui function
      (density functional descriptor) and the local hard and soft acids and bases
      principle. The results obtained open the possibility of analyzing the resonance
      contributors and the resonance hybrid in terms of the electronic density.
      [structure--see text]

PMID- 15151414
TI  - Trans-selective conversions of gamma-hydroxy-alpha,beta-alkynoic esters to gamma
      hydroxy-alpha,beta-alkenoic esters.
AB  - Gamma-hydroxy-alpha,beta-acetylenic esters are used as precursors to prepare
      gamma-hydroxy-alpha,beta-alkenoic esters by means of trans-selective additions of
      two hydrogen atoms or one hydrogen atom and one iodine atom across the triple
      bonds. These methods allow for the preparation of beta-substituted and alpha,beta
      disubstituted alkenoic esters in highly stereoselective manners. [reaction--see
      text]

PMID- 15151415
TI  - Dicationic intermediates involving protonated amides: dual modes of reactivity
      including the acylation of arenes.
AB  - In the Bronsted superacid CF(3)SO(3)H (triflic acid), amides are able to form
      reactive, dicationic electrophiles. It is shown that these dicationic
      intermediates participate in two distinctly different types of electrophilic
      reactions. The protonated amide increases the reactivity of an adjacent
      electrophilic group, and the protonated amide group itself shows enhanced
      reactivity arising from an adjacent cationic charge. In the latter case, several
      types of amides are even capable of reacting with benzene by Friedel-Crafts
      acylation. [reaction--see text]

PMID- 15151416
TI  - Lithiation at the 6-position of uridine with lithium hexamethyldisilazide:
      crucial role of temporary silylation.
AB  - Lithium hexamethyldisilazide (LiHMDS) can mediate silylation at the 6-position of
      uridine, although LiHMDS alone is not able to generate the C-6-lithiated uridine.
      Experimental results showed that temporary silylation of O-4 (or N-3) of the
      uracil ring triggers the C-6 lithiation with LiHMDS. This finding allowed us to
      develop an efficient intramolecular alkylation of 5'-deoxy-5'-iodouridine to
      furnish 6,5'-C-cyclouridine. [reaction--see text]

PMID- 15151417
TI  - Photochemical deuterium exchange of the m-methyl group of 3-methylbenzophenone
      and 3-methylacetophenone in acidic D2O.
AB  - Photolysis of the title compounds in acidic aqueous solution results in
      "activation" of the distal m-methyl group, resulting in deuterium exchange (Phi
      approximately 0.1) when D(2)O is used. The reaction is not observed in neutral
      aqueous solution or in deuterated organic solvents such as CD(3)CN. The reaction
      is best rationalized by a mechanism involving initial protonation at the carbonyl
      oxygen of the triplet excited state. [reaction: see text]

PMID- 15151418
TI  - A re-examination of the circular dichroism of the calicheamicin enediyne/dienone
      chromophoric interaction.
AB  - A series of calicheamicin derivatives have been made in an effort to delineate
      the origin of the strong circular dichroism (CD) of calicheamicin reported
      previously. The CD spectrum of calicheamicin (I) was compared with that of
      fragments II and III, which contain either the enediyne/dienone or a thiobenzoate
      chromophore alone. NaBH(4) reduction of calicheamicin produced two analogues (IV
      and V) that have no dienone. This allowed the assessment of possible exciton
      coupling between the enediyne on the warhead and the thiobenzoate on the tail. It
      was found that the strong negative 312/272 nm exciton split in the CD of
      calicheamicin is due largely to the enediyne/dienone interaction. Contributions
      from the thiobenzoate or its interaction with the enediyne have been ruled out.
      [structure: see text]

PMID- 15151419
TI  - Syntheses of conformationally constricted molecules as potential NAALADase/PSMA
      inhibitors.
AB  - Two six-membered ring targeted analogues of PSMA inhibitors (4a and 4b) were
      designed on the basis of a computational analysis and synthesized. (E,Z)-Diene 10
      was subjected to the nitroso Diels-Alder reaction to give the 1,4-trans six
      membered ring adduct, 4a. The cis isomer 4b was derived from similar nitroso
      cycloaddition reactions with the corresponding (E,E)-diene and separately from
      cyclohexadiene. The IC(50) values of 4a and 4b in a NAALADase assay were found to
      be 0.9 and 0.1 microM, respectively. [reaction: see text]

PMID- 15151420
TI  - CuI/N,N-dimethylglycine-catalyzed coupling of vinyl halides with amides or
      carbamates.
AB  - The CuI-catalyzed coupling reaction of vinyl halides with amides or carbamates
      proceeds well at room temperature to 80 degrees C in dioxane to give enamides
      using N,N-dimethylglycine as the promoter and Cs(2)CO(3) as the base. The
      geometry of the C-C double bond is retained during the reaction course.
      [reaction: see text]

PMID- 15151421
TI  - A new general access to either type of Securinega alkaloids: synthesis of
      securinine and (-)-allonorsecurinine.
AB  - The syntheses of securinine and (-)-allonorsecurinine have been achieved starting
      from easily available alpha-amino acid derivatives and using as key steps a RCM
      and a Heck reaction for the formation of rings D and C, respectively. [reaction:
      see text]

PMID- 15151422
TI  - Formal synthesis of (+/-)-guanacastepene A: a tandem ring-closing metathesis
      approach.
AB  - A concise route to a key intermediate in the total synthesis of guanacastepene A
      is described. The main features include the simultaneous construction of the
      seven- and six-membered rings, using a tandem ring-closing metathesis and a
      stereoselective introduction of the oxygenated function at the C5 position.
      [reaction: see text]

PMID- 15151424
TI  - What are the limits to the size of effective dynamic combinatorial libraries?
AB  - Using simple computer simulations of model dynamic combinatorial libraries, we
      show that the best binders can be amplified to useful concentrations in libraries
      containing 10-10(6) compounds. [structure: see text]

PMID- 15151425
TI  - Palladium pincer complex-catalyzed allylic stannylation with hexaalkylditin
      reagents.
AB  - Palladium pincer complex (1)-catalyzed stannylation of allyl chloride,
      phosphonate, and epoxide substrates (4a-h) could be performed with hexaalkylditin
      reagents (3) under mild neutral reaction conditions. This catalytic reaction
      proceeds via palladium(II) intermediates without involvement of allyl-palladium
      complexes, and therefore the allylstannane product does not interfere with the
      palladium catalyst. Use of a combined catalytic system (1 + 2) allowed the
      development of an effective one-pot procedure for allylation of aldehyde and
      imine electrophiles. [reaction: see text]

PMID- 15151423
TI  - Synthesis of quaternary amino acids bearing a (2'Z)-fluorovinyl alpha-branch:
      potential PLP enzyme inactivators.
AB  - Protected alpha-formyl amino acids, themselves available from the corresponding
      alpha-vinyl amino acids, are stereoselectively transformed into the (Z)
      configured alpha-(2'-fluoro)vinyl amino acids via a three-step sequence. The
      route employs McCarthy's reagent, diethyl alpha-fluoro-alpha
      (phenylsulfonyl)methyl phosphonate, and proceeds via the intermediate (E)-alpha
      fluorovinyl sulfones and (E)-alpha-fluorovinylstannanes. The latter may either be
      exploited as novel cross-coupling partners for fluorovinyl branch extension or be
      globally deprotected, to provide the title compounds. [structure: see text]

PMID- 15151426
TI  - Development of chiral pincer palladium complexes bearing a pyrroloimidazolone
      unit. Catalytic use for asymmetric Michael addition.
AB  - Novel pincer palladium complexes having chiral hexahydro-1H-pyrrolo[1,2
      c]imidazolone groups were designed and prepared. Catalytic asymmetric Michael
      addition of isopropyl 2-cyanopropionate to ethyl vinyl ketone was catalyzed by
      the chiral pincer palladium complex to give isopropyl 2-cyano-2-methyl-5
      oxoheptanoate with high enantioselectivity (up to 83% ee). [structure: see text]

PMID- 15151427
TI  - General synthesis of meso-amidoporphyrins via palladium-catalyzed amidation.
AB  - A series of meso-amidoporphyrins were facilely synthesized by direct reactions of
      meso-brominated porphyrins with amides via palladium-catalyzed amidation
      reaction. Using a combination of palladium precursor Pd(OAc)(2) or Pd(2)(dba)(3)
      and phosphine ligand Xantphos, both 5-bromo-10,20-diphenylporphyrin and 5,15
      dibromo-10,20-diphenylporphyrin, as well as their zinc complexes, can be
      effectively coupled with a wide variety of amides to give the corresponding mono-
      and bis-substituted meso-amidoporphyrins in high yields under mild conditions.
      [reaction: see text]

PMID- 15151428
TI  - Xyloccensins O and P, unique 8,9,30-phragmalin ortho esters from Xylocarpus
      granatum.
AB  - Two unique 8,9,30-phragmalin ortho esters, xyloccensins O (1) and P (2), were
      isolated from the mangrove plant Xylocarpus granatum. They are a new type of
      ortho ester of phragmalin. The structures were determined by spectroscopic and
      single-crystal X-ray diffraction techniques. The biogenetic pathway to these new
      phragmalins was also proposed. [structure: see text]

PMID- 15151429
TI  - Formation of enamides via palladium(II)-catalyzed vinyl transfer from vinyl
      ethers to nitrogen nucleophiles.
AB  - Palladium(II) complexes catalyze the formation of enamides via the formal cross
      coupling reaction between nitrogen nucleophiles and vinyl ethers. These vinyl
      transfer reactions proceed in good yields with amide, carbamate, and sulfonamide
      nucleophiles, and the optimal catalyst is (DPP)Pd(OCOCF(3))(2) (DPP = 4,7
      diphenyl-1,10-phenanthroline). [reaction: see text]

PMID- 15151430
TI  - A novel synthesis of functionalized allylsilanes.
AB  - A novel facile synthesis of substituted and functionalized allylsilane has been
      developed. This essentially one-pot procedure involves (1)
      (dimethylphenylsilyl)methyl cerium chloride addition to cyclopropyl ketone and
      (2) MgI(2) etherate-mediated Julia homoallylic transposition of the corresponding
      cyclopropyl carbinol. The bifunctional homoiodo allylsilanes, readily accessible
      by this method, would be useful and versatile synthons in organic synthesis.
      [reaction: see text]

PMID- 15151431
TI  - Stereoselective synthesis of cis-1,3-disubstituted cyclobutyl kinase inhibitors.
AB  - Two synthetic routes to a series of structurally novel kinase inhibitors
      containing a cis-1,3-disubstituted cyclobutane are described. The first route
      utilized addition of 3-aminocyclobutanol to 1,4-dinitroimidazole 5 as the crucial
      step in preparing 1, whereas the second route employed a novel 1,4-addition of 4
      nitroimidazole 18 to in situ generated cyclobutenone 17 as the key reaction. This
      allowed for a stereoselective and shorter synthesis that eliminated the use of
      potentially explosive 1,4-dinitroimidazole 5. [structure: see text]

PMID- 15151432
TI  - Phosphine-mediated [4 + 2] annulation of bis(enones): a Lewis base catalyzed
      "mock Diels-Alder" reaction.
AB  - Lewis-base-catalyzed cycloisomerization of bis(enones) to decalins has been
      demonstrated as an alternative to the traditional Lewis acid catalyzed Diels
      Alder cycloaddition. In this process, a trialkylphosphine mediates both bond
      formation steps in two distinct catalytic cycles. The single-pot operation
      generates two carbon-carbon bonds and up to five contiguous stereocenters in one
      step, starting from achiral, aliphatic substrates; eight examples are provided.
      [reaction: see text]

PMID- 15151433
TI  - Amine-salt-controlled, catalytic asymmetric conjugate addition of various amines
      and asymmetric protonation.
AB  - The combined use of chiral Pd complex 2 and amine salt enabled completely
      regulated release of free nucleophilic amine. Under these conditions, an
      efficient catalytic asymmetric conjugate addition of various amines was achieved
      to afford beta-amino acid derivatives in high chemical yields with up to 98% ee.
      Furthermore, a highly enantioselective protonation in 1,4-addition of amine was
      also developed. [reaction: see text]

PMID- 15151434
TI  - Total synthesis of (-)-borrelidin.
AB  - The total synthesis of borrelidin has been achieved. The best feature of our
      synthetic route is SmI(2)-mediated intramolecular Reformatsky-type reaction for
      macrocyclization after esterification between two segments. The two key segments
      were synthesized through chelation-controlled carbotitanation, chelation
      controlled hydrogenation, stereoselective Reformatsky reaction, and
      MgBr(2).Et(2)O-mediated chelation-controlled allylation. [reaction: see text]

PMID- 15151435
TI  - Extending Pummerer reaction chemistry. Application to the oxidative cyclization
      of indole derivatives.
AB  - Treatment of 2-(phenylsulfinyl)indoles bearing a pendant nucleophile at C(3) with
      Tf(2)O/lutidine triggers a Pummerer-like cyclization to furnish 3,3-spirocyclic-2
      (phenylthio)indolenine products, which can, in turn, be hydrolyzed to 3,3
      spirocyclic oxindoles. [reaction: see text]

PMID- 15151436
TI  - CpRuIIPF6/quinaldic acid-catalyzed chemoselective allyl ether cleavage. A simple
      and practical method for hydroxyl deprotection.
AB  - A cationic CpRu(II) complex in combination with quinaldic acid shows high
      reactivity and chemoselectivity for the catalytic deprotection of hydroxyl groups
      protected as allyl ethers. The catalyst operates in alcoholic solvents without
      the need for any additional nucleophiles, satisfying the practical requirements
      of operational simplicity, safety, and environmental friendliness. The wide
      applicability of this deprotection strategy to a variety of multifunctional
      molecules, including peptides and nucleosides, may provide new opportunities in
      protective group chemistry. [structure: see text]

PMID- 15151439
TI  - Therapy techniques for cleft palate speech and related disorders.

PMID- 15151437
TI  - Use of acid fluorides increases the scope of the reductive acylation of esters.
AB  - The use of acyl fluorides in the Rychnovsky reductive acylation of esters allows
      a variety of esters to be converted to their corresponding alpha-acyloxy ethers
      in good to excellent yields, without the need to sacrifice an extra equiv of
      carboxylic acid functionality. [structure: see text]

PMID- 15151440
TI  - Global strategies to reduce the health care burden of craniofacial anomalies:
      report of WHO meetings on international collaborative research on craniofacial
      anomalies.
AB  - Although several significant research projects have arisen from international
      cooperation, especially in the field of genetics, these have been the exception
      rather than the rule. However, those of us who had the privilege and delight of
      participating in the World Health Organization meetings were struck by a common
      realization of the vast potential of systematic international cooperation. It is
      clear that the global model will be the most effective approach for tackling the
      big questions in craniofacial anomalies, be they concerned with cause, treatment,
      or prevention. This report will serve as a road map for making collaboration the
      rule and not the exception and hopefully be a stimulus for the creation of
      partnerships between international research teams and funding agencies.

PMID- 15151441
TI  - Variations in facial soft tissues of italian individuals with ectodermal
      dysplasia.
AB  - OBJECTIVE: To supply quantitative information about the facial soft tissues of
      patients with ectodermal dysplasia (ED). DESIGN, SETTING, AND PATIENTS: The three
      dimensional coordinates of soft tissue facial landmarks were obtained using an
      electromagnetic digitizer in 20 Caucasian patients with ED (11 male and 9 female
      patients aged 7 to 41 years) and 391 healthy controls (163 female and 228 male
      subjects of comparable ages). From the landmarks, 15 facial dimensions and two
      angles 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 patients and
      reference subjects: the mean z-score (an index of overall facial size) and its
      standard deviation, called the craniofacial variability index (an index of facial
      harmony). RESULTS: In patients with ED, a large variability was found for both
      the mean z-score and the craniofacial variability index. On average, the patients
      had a somewhat smaller facial size than the normal individuals, with a global
      disharmonious appearance. Overall, 70% of patients fell outside the quantitative
      definitions for normal facial size, harmony or both. When examining the
      distribution of the single z-scores of the 17 selected measurements, variable
      patterns were found, without consistent effects of age or sex. CONCLUSIONS: The
      facial soft tissue structures of patients with ED differed both in size and shape
      from those of normal controls of the same age, sex, and ethnic group.

PMID- 15151442
TI  - Three-dimensional analysis of maxillary and mandibular growth increments.
AB  - OBJECTIVE: To analyze changes in the facial, maxillary, and mandibular skeleton
      in the vertical, sagittal, and transverse dimensions during an orthodontically
      relevant period of dentofacial development (i.e., between 7 and 15 years of age).
      SUBJECTS AND METHOD: This longitudinal study comprised posteroanterior (PA) and
      lateral cephalograms at 7, 9, 11, 13, and 15 years of 18 untreated Class I
      subjects with good occlusion. Transverse growth (width) was analyzed on the basis
      of PA cephalograms and sagittal (depth) and vertical (height) growth by means of
      lateral cephalograms. For each linear measurement, mean percentage increases were
      calculated relative to the size at 7 years of age. RESULTS AND CONCLUSIONS:
      Between 7 and 15 years of age, in the whole facial skeleton and the maxilla,
      percentage increases were most pronounced in the vertical dimension when compared
      with the sagittal and transverse dimensions. In the mandible, the largest
      percentage increases were found in both sexes for vertical growth of the ramus,
      followed by sagittal growth (body length) and then mandibular width. In the
      sagittal dimension, development was more pronounced in the mandible (at pogonion
      more than at B point) than in the maxilla (A point). With respect to vertical
      growth, percentage increases in posterior face height exceeded the increases in
      anterior face height. When facial shape changes were analyzed between 7 and 15
      years of age in both sexes, the ratio facial height/facial width increased and
      the ratio facial depth/ facial height decreased, which points toward an age
      related increasing influence of vertical development.

PMID- 15151443
TI  - Oral rehabilitation of an orthodontic patient with cleft lip and palate and
      hypodontia using secondary bone grafting, osseo-integrated implants, and
      prosthetic treatment.
AB  - OBJECTIVE: Complete skeletal and dental reconstruction of the anterior maxilla is
      of great importance to patients with cleft lip and palate. Accordingly, osseo
      integrated implants have been utilized for dental reconstruction after secondary
      bone grafting. In this report, the orthodontic management of a patient with
      unilateral cleft lip and plate with associated hypodontia is described. The
      patient was treated with comprehensive orthodontic treatment in addition to
      secondary bone grafting, and dental reconstruction was achieved with a
      combination of osseo-integrated implants and fixed prosthodontic treatment.

PMID- 15151444
TI  - A review of feeding interventions for infants with cleft palate.
AB  - OBJECTIVE: A literature review was conducted to identify feeding interventions
      recommended for infants with cleft conditions. Selected articles were critically
      appraised using an evidence-based practice framework to determine the strength of
      the evidence underpinning each intervention. DESIGN: Electronic databases were
      searched for reports of cleft palate feeding interventions. The selected articles
      were coded as being data driven or not; those containing data were then
      critically appraised using a recognized evidence hierarchy. Finally, each report
      was ascribed a level of evidence (from I to IV), depending on the quality of data
      presented. RESULTS: Fifty-five articles published between 1955 and 2002 were
      reviewed. There are currently no completed systematic reviews relevant to this
      body of literature (level I evidence). Two well-designed randomized controlled
      trials (level II evidence) were found. These were considered to provide the
      strongest evidence for feeding intervention techniques. These articles described
      a combination of interventions, including early feeding and nutrition education,
      as well as assisted feeding methods for infants with isolated cleft conditions.
      Three examples of level III.3 evidence were also found. Fifty (91%) of 55
      articles reviewed were non-data-driven reports of expert opinion (level IV).
      CONCLUSIONS: A paucity of evidence rated as either moderate or strong prevailed,
      underscoring the need for ongoing scientific evaluation of feeding interventions
      used with infants who have cleft palate. A number of factors, including the
      heterogeneity of samples studied, lack of replication of trials, and small sample
      sizes, affected the type and strength of evidence underpinning specific feeding
      interventions.

PMID- 15151445
TI  - Buccinator sandwich pushback: a new technique for treatment of secondary
      velopharyngeal incompetence.
AB  - OBJECTIVE: A small percentage of patients have inadequate velopharyngeal closure,
      or secondary velopharyngeal incompetence, following primary palatoplasty. Use of
      the buccinator musculomucosal flap has been described for primary palate repair
      with lengthening, but its use in secondary palate lengthening for the correction
      of insufficient velopharyngeal closure has not been described. This study
      presents the results of a series of patients who had correction of secondary
      velopharyngeal incompetence using bilateral buccinator musculomucosal flaps used
      as a sandwich. PATIENTS: In this prospective study between 1995 and 1998, a group
      of 16 patients with insufficient velopharyngeal closure as determined by speech
      assessment and videoradiography were selected. Nasopharyngoscopy was carried out
      in addition in a number of cases. Case selection was a result of these
      investigations and clinical examination in which the major factor in
      velopharyngeal insufficiency was determined to be short palatal length. DESIGN:
      The patients underwent palate lengthening using bilateral buccinator
      musculomucosal flaps as a sandwich. All patients were assessed 6 months
      postoperatively. The operative technique, postoperative course, and recorded
      postoperative complications including partial/total flap necrosis and residual
      velopharyngeal insufficiency were evaluated. Preoperative and postoperative
      speech samples were rated by an independent speech therapist. RESULTS: Ninety
      three percent (15 of 16) had a significant improvement in velopharyngeal
      insufficiency, and 14 patients had no hypernasality postoperatively. Both cases
      of persistent mild hypernasality had had a recognized postoperative complication.
      CONCLUSION: The sandwich pushback technique for the correction of persistent
      velopharyngeal incompetence was successful in achieving good speech results.

PMID- 15151446
TI  - A modified muscle-activated maxillary orthopedic appliance for presurgical
      nasoalveolar molding in infants with unilateral cleft lip and palate.
AB  - OBJECTIVE: The purpose of this article is to describe a modified appliance and
      treatment approach for presurgical nasoalveolar molding in infants with
      unilateral cleft lip and palate. METHODS: This approach uses a plate held in with
      outriggers, which prevents the cleft-widening effect of the tongue, helps with
      tongue tip placement, and utilizes the functional movements of the facial
      musculature to guide and relocate the major segment medially to its normal
      position. Nasal molding is undertaken after most of the lateromedial correction
      of the alveolar position. CONCLUSIONS: This technique helps to improve alveolar
      position, nasal septum alignment, nasal symmetry, and nasal tip projection prior
      to lip repair.

PMID- 15151448
TI  - Clinical findings in four Brazilian families affected by Saethre-Chotzen syndrome
      without TWIST mutations.
AB  - OBJECTIVE: To analyze the dysmorphological variability and to investigate the
      presence of mutations in the exon 1 of TWIST gene using direct sequencing in
      Brazilian families presenting with Saethre-Chotzen Syndrome (SCS). METHODS: Four
      families with 24 patients diagnosed as having features of SCS were studied.
      Phenotypic characteristics of all patients were inventoried. The investigation
      protocol included anamnesis, dysmorphological examination, abdominal ultrasound,
      spine and cranium x-ray, chromosomal analysis on GTG banding, and screening for
      mutations in the exon 1 of TWIST gene. RESULTS: Frequent facial features included
      brachycephaly (24 of 24), facial asymmetry (20 of 24), prominent ears crus (15 of
      24), low-set ears (14 of 24), maxillary hypoplasia (13 of 24), prominent nasal
      bridge (13 of 24), ptosis of the eyelids (12 of 24), and low-set frontal hairline
      (12 of 24). Limb abnormalities such as partial hand cutaneous syndactyly (18 of
      24), clinodactyly (13 of 24), and broad great toes (13 of 24), and partial
      cutaneous syndactyly of the feet (9 of 24) were also detected. Among radiological
      findings were relevant bicoronal (eight of nine) and unicoronal (one of nine)
      craniosynostosis, digital impressions (eight of nine), bilateral parietal
      foramina (two of nine), partial fusion 1 and 2 degrees costal arches (two of
      nine) and bifid spine on lumbar vertebra (two of nine). GTG-banding chromosomal
      analyses were normal. No TWIST gene mutations were found. CONCLUSIONS: Affected
      individuals in these four SCS families may carry mutations in other genes of the
      same developmental pathway. Considering the complexity of the genes involved in
      skull-limbs development, an accurate dysmorphological evaluation in patients with
      SCS and their families is especially important for genetic counseling.

PMID- 15151447
TI  - Transverse craniofacial features and their genetic predisposition in families
      with nonsyndromic unilateral cleft lip and palate.
AB  - OBJECTIVE: The purpose of this study was to evaluate the transverse craniofacial
      form in families with nonsyndromic cleft lip and palate (NSCLP). It was
      hypothesized that affected as well as noncleft NSCLP family members are
      characterized by a common array of craniofacial features that differ from the
      general population. DESIGN: This was a prospective cross-sectional investigation
      that included affected children with NSCLP and their noncleft parents and
      siblings. PATIENTS, PARTICIPANTS: A total of 114 subjects (14 affected girls, 17
      affected girls, 15 unaffected male siblings, 10 unaffected female siblings, 29
      unaffected biological mothers, and 29 unaffected biological fathers) were
      included. Subject records comprised of posteroanterior cephalometric radiographs
      obtained from all 114 subjects. MAIN OUTCOME MEASURES: The width of midfacial
      structures, including the orbit and nose, was increased in NSCLP families,
      compared with published norms. Interestingly, the face was disproportionally
      wider in relation to total facial height. The transverse craniofacial form of
      children with or without clefts significantly correlated with that of their
      parents. Mothers displayed strong correlation with their affected and unaffected
      sons, whereas fathers correlated to their daughters, suggesting a possible sex
      linked developmental influence. CONCLUSION: Better understanding of the genetic
      inheritance of craniofacial features associated with cleft lip and palate may
      ultimately contribute to the development of cleft risk assessment methods.

PMID- 15151449
TI  - A rare craniofacial cleft: numbers 7, 2, and 3 clefts accompanied by a single
      median lip pit.
AB  - OBJECTIVE: A unique case of a unilateral partial Tessier no. 7 cleft accompanied
      by no. 2 and 3 clefts along with a single median lip pit is presented. The
      history, genetics, epidemiology, classifications, embryology, pathogenesis, and
      correction techniques are briefly reviewed. After an extensive review of the
      literature, we conclude that this particular constellation of anomalies has not
      previously been described.

PMID- 15151450
TI  - Maxillary and mandibular displacement in hemifacial microsomia: a longitudinal
      Roentgen stereometric study of 21 patients with the aid of metallic implants.
AB  - OBJECTIVE: To record maxillary and mandibular displacement with articular growth
      and in response to bimaxillary surgical repositioning in patients with hemifacial
      microsomia (HFM) and to observe ipsilateral corpus/ramus growth in severely
      affected children. DESIGN: Prospective roentgen stereometric analysis (mean age 7
      years 10 months to 18 years 0 months) and retrospective profile and panoramic
      roentgenograms. Mean total observation period was 9 years 1 month. SETTING:
      Department of Plastic and Reconstructive Surgery, Malmo University Hospital
      (Malmo, Sweden). PATIENTS: Twenty-one patients consecutively diagnosed from 1976
      through 1988 with HMF, five of whom had bimaxillary surgery. INTERVENTIONS:
      Surgery was performed at the Department of Plastic and Reconstructive Surgery.
      Implants were inserted at the initial reconstructive surgical procedure under
      general anesthesia. Roentgen examinations were performed in connection with
      continued clinical evaluations and treatment. MAIN OUTCOME MEASURES: Stereo
      roentgenograms were digitized at the Department of Orthopedic Surgery, Malmo
      University Hospital (Malmo, Sweden). RESULTS: Displacement of the jaws with
      articular growth and in response to bimaxillary surgical repositioning varied
      interindividually with no apparent common pattern. Relapse displacement occurred
      several years after bimaxillary surgery. Mandibular growth changes were found in
      the corpus/ramus area and alveolar process on the affected side. CONCLUSIONS: A
      marked interindividual variability of maxillary and mandibular displacement
      indicates that the relevance of statistical analysis of HFM growth data may be
      questioned. We would suggest that precise and accurate longitudinal recordings of
      growth and response to surgery in individual HFM patients be more appropriate.

PMID- 15151451
TI  - Nasalance scores in wearers of a palatal lift prosthesis in comparison with
      normative data for Japanese.
AB  - OBJECTIVE: This study was designed to examine whether nasalance score is changed
      in association with placement of a palatal lift prosthesis (PLP) and whether
      normative data previously reported are applicable to evaluate the effect of a PLP
      on velopharyngeal function as it relates to nasality. DESIGN: Nasalance scores
      were obtained as subjects read the Kitsutsuki Passage three times with the PLP in
      place and then removed. PARTICIPANTS: Forty-three children (mean age 9.0 years,
      SD = 3.6 years) with repaired cleft palate who were treated with a PLP were
      selected as subjects. Their speech was characterized by nasal emission of air,
      slight hypernasality without a PLP but within normal limits with a PLP in place,
      or both. MAIN OUTCOME MEASURES: Comparisons were made between normative scores
      and the average mean nasalance score of subjects with and without the PLP.
      RESULTS: Average values of the mean nasalance score for subjects were 17.3% (SD
      7.6%) with the PLP in place and 33.5% (SD 13.3%) without the PLP in place. These
      scores were greater than the mean score of 9.1% (SD 3.9%) obtained from normal
      controls previously reported. CONCLUSION: A PLP can decrease nasalance scores for
      speakers with repaired cleft palate who exhibit velopharyngeal incompetence. It
      was suggested that the normative score obtained from normal adult speakers is not
      applicable to evaluate the effect of a PLP to improve velopharyngeal function for
      children wearing the PLP.

PMID- 15151452
TI  - Rapid maxillary expansion after secondary alveolar bone graft in a patient with
      bilateral cleft lip and palate.
AB  - OBJECTIVE: To verify the effects of rapid maxillary expansion performed after
      secondary alveolar bone graft in one patient. SETTING: Department of Orthodontics
      of the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao
      Paulo. PATIENT(S): The patient had bilateral cleft lip and palate, had already
      had a bone graft, and showed a relapsing maxillary constriction in need of
      correction. INTERVENTION: A fixed dental-mucous-bone-supported expander corrected
      the maxillary constriction. MAIN OUTCOME MEASURE(S): Measurements were obtained
      from dental casts, including transverse dimensions (intercanine distance [IC],
      interfirst premolar distance [IP], and interfirst molar distance [IM]) and
      measurements of the grafted area (interfirst premolar/central incisors [IPI] and
      interfirst premolar/canine [IPC]) to observe the changes. Clinical and
      radiographic analyses were done through direct view. RESULTS: The occlusal
      radiograph of the maxilla after expansion showed opening of the intermaxillary
      suture in the premaxillary area, which was clinically confirmed by the diastema
      between the maxillary central incisors. No radiographic alteration was observed
      in the grafted area. The transverse measurements of the dental casts (IC, IP, and
      IM) showed a significant increase. The measurements of the teeth adjacent to the
      grafted area, IPI and IPC, increased. CONCLUSIONS: The orthopedic effect of rapid
      maxillary expansion after bone graft was verified. Nevertheless, additional
      studies are necessary to define any side effects in patients submitted to bone
      graft.

PMID- 15151453
TI  - Chronology of deciduous teeth eruption in children with cleft lip and palate.
AB  - OBJECTIVE: To determine the chronology and sequence of eruption of the deciduous
      teeth in children with complete unilateral cleft lip and palate. DESIGN: Cross
      sectional study. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies,
      University of Sao Paulo, Bauru, Sao Paulo, Brazil. SAMPLE: A total of 435
      children aged 0 to 48 months who presented with complete unilateral cleft lip and
      palate. RESULTS: All teeth on the cleft side in both jaws for both sexes
      presented a higher mean age of eruption than their homologues at the noncleft
      side. This difference was statistically significant for the maxillary lateral
      incisor, maxillary cuspid, and mandibular lateral incisor. There was a
      statistically significant sex difference regarding the mean age of eruption only
      for the maxillary second molar for the girls and mandibular cuspid for the boys.
      The maxillary lateral incisor on the cleft side was the last tooth to erupt, thus
      modifying the sequence of eruption of the deciduous teeth. CONCLUSIONS: The
      results suggest the interference of the cleft on the chronology of eruption of
      the deciduous teeth that are directly related to it.

PMID- 15151454
TI  - Epidemiology of cleft palate in Europe: implications for genetic research.
AB  - OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN
      AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified
      (1980 through 1996) from more than 6 million births from the EUROCAT network of
      30 registers in 16 European countries. RESULTS: Significant differences in
      prevalence in Europe between registries and within countries were observed. A
      total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated
      with other defects such as multiple congenital anomalies, and 1046 (27.2%) were
      in recognized conditions. The study confirmed the tendency toward female
      prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78)
      even if SR inversion is reported in some registries. A specific association with
      neural tube defects (NTDs) in some registers is reported. CONCLUSION: The
      differences identified in Europe (prevalence, sex, associated anomalies) can be
      only partially explained by methodological reasons because a common methodology
      was shared among all registries for case ascertainment and collection, and CP is
      an easy detectable condition with few induced abortions. The complex model of
      inheritance and the frequently conflicting results in different populations on
      the role of genes that constitute risk factors suggest the presence of real
      biological differences. The association of CP/NTD in an area with a high
      prevalence of NTDs can identify a group of conditions that can be considered
      etiologically homogeneous. The epidemiological evaluation can guide genetic
      research to specify the role of etiological factors in each different population

PMID- 15151455
TI  - Evaluation of fatigability of the levator veli palatini muscle during continuous
      blowing using power spectra analysis.
AB  - OBJECTIVE: The purpose of this study was to compare the fatigability of the
      levator veli palatini (LVP) muscle during blowing in speakers who exhibit
      velopharyngeal incompetence with that from normal speakers by means of power
      spectra analysis. DESIGN: All subjects were instructed to blow into a tube for
      more than 10 seconds at maximum possible effort. The LVP muscle activity
      (electromyography) was sampled at 2 kHz for 10 seconds from the time when the
      oral air pressure during blowing was stabilized. These samples were subjected to
      Fast Fourier Transfer analysis with analytic windows of 0.5-second width. The
      electromyography mean power frequency slope with respect to time for each subject
      was estimated. PARTICIPANTS: Three speakers with repaired cleft palate and three
      normal speakers were selected as subjects. RESULTS: The slopes of the regression
      lines for all three subjects with repaired cleft palate were negatively signed
      with statistical significance (t test, p <.01). The slopes for all of the normal
      speakers were negatively signed, but these were not statistically significant.
      CONCLUSION: These results suggest that the LVP muscle of speakers with repaired
      cleft palate who exhibit varying degrees of velopharyngeal dysfunction may
      deteriorate more easily in comparison with the LVP muscle of normal speakers.

PMID- 15151456
TI  - Antipsychotic-induced weight gain and metabolic abnormalities: implications for
      increased mortality in patients with schizophrenia.

PMID- 15151463
TI  - On-pump coronary artery bypass grafting may have better long-term effects.

PMID- 15151464
TI  - Bivalirudin: an anticoagulant option for percutaneous coronary intervention.
AB  - Coronary artery thrombosis is usually triggered by platelet-rich thrombus
      superimposed on a spontaneously or mechanically disrupted atherosclerotic plaque.
      Thrombin and platelets both play a role in this process. Unfractionated heparin
      and aspirin have served as cornerstones in the prevention and treatment of
      intracoronary thrombus, but unfractionated heparin has several limitations that
      necessitate the use of adjunctive therapies, such as glycoprotein IIb/IIIa
      receptor inhibitors and clopidogrel, in order to reduce the risk of ischemic
      events. These combination therapies, however, typically increase the risk for
      bleeding complications, as well as the cost and complexity of treatment.
      Bivalirudin (Angiomax, The Medicines Company), a thrombin-specific anticoagulant,
      does not share heparin's limitations. Bivalirudin appears to provide clinical
      advantages over unfractionated heparin therapy in acute coronary syndrome
      patients and those undergoing percutaneous coronary intervention, without
      increasing cost or complexity of treatment for most patients.

PMID- 15151465
TI  - Antithrombotic therapy in atrial fibrillation: ximelagatran, an oral direct
      thrombin inhibitor.
AB  - The oral direct thrombin inhibitor ximelagatran (Exanta, AstraZeneca) is rapidly
      absorbed, is efficiently bioconverted to the active form, melagatran
      (AstraZeneca) and has shown efficacy and relative safety as an anticoagulant for
      prophylaxis and therapy of thromboembolism. Two Phase III trials, Stroke
      Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF V),
      have tested the hypothesis that oral ximelagatran, administered 36 mg twice daily
      without coagulation monitoring or dose adjustment, prevents stroke and systemic
      embolism at least as effectively as adjusted-dose warfarin (international
      normalized ratio, 2.0-3.0) in patients with nonvalvular atrial fibrillation. Both
      were randomized, multicenter trials (n > 3000 per trial) with blinded end-point
      assessment. The open-label SPORTIF III trial confirmed the noninferiority of
      ximelagatran versus warfarin. Publication of the full results from SPORTIF V is
      pending.

PMID- 15151466
TI  - Bosentan.
AB  - Bosentan (Tracleer, Actelion Pharmaceuticals Ltd) is an oral dual endothelin
      receptor antagonist approved for use in functional class III to IV pulmonary
      arterial hypertension. In two placebo-controlled trials, patients receiving
      bosentan showed improved functional class, 6-minute walk distance and
      hemodynamics over a 12- to 16-week period. Follow-up data over 3 years has shown
      few deteriorations,with the majority of patients maintaining their response to
      bosentan alone. Investigations exploring the use of bosentan as an add-on agent
      to intravenous epoprostenol (Flolan, GlaxoSmithKline Plc) in those with the most
      severe disease are ongoing. Bosentan may also have antifibrotic properties and
      its use in pulmonary fibrosis is being explored. Ease of administration of
      bosentan with twice-daily oral dosing will provide many patients with pulmonary
      hypertension an option for treatment without the risks and discomforts of
      continuous intravenous medication.

PMID- 15151467
TI  - Treprostinil for pulmonary hypertension.
AB  - Treprostinil (Remodulin, United Therapeutics) is a stable, long-acting
      prostacyclin analog, which has been shown to improve clinical state, functional
      class, exercise capacity and quality of life in patients with pulmonary arterial
      hypertension, an uncommon disease with poor prognosis. The drug is administered
      as a continuous subcutaneous infusion using a portable miniature delivery system.
      Side effects include facial flush, headache, jaw pain, abdominal cramping and
      diarrhea. These are all typical of prostacyclin impregnation and manageable by
      symptom-directed dose adjustments. Infusion site pain, a more serious side
      effect, may limit the treatment in 10% of patients. Otherwise, treprostinil has
      an excellent safety profile and compares favorably with reference continuous
      intravenous epoprostenol (Flolan, GlaxoSmithKline) therapy. Treprostinil has a
      place in currently proposed treatment algorithms of pulmonary arterial
      hypertension.

PMID- 15151468
TI  - Impact of bariatric surgery on cardiac structure, function and clinical
      manifestations in morbid obesity.
AB  - Obesity results from the excessive accumulation of fat. Risk of premature death
      is doubled compared to nonobese individuals, and risk of death from
      cardiovascular disease is increased fivefold. In patients with morbid obesity, a
      variety of adaptations and alterations in cardiac structure and function occur in
      the individual, as an excess amount of adipose tissue accumulates. The high long
      term failure rate of diet intervention is well acknowledged by the clinician.
      Surgery for severe obesity has evolved during the last 40 years. Many surgical
      techniques have been described and abandoned. Nevertheless, numerous different
      techniques are still in use today. Weight loss has beneficial impacts on
      functional and structural cardiac status and will be reviewed in this report.

PMID- 15151469
TI  - Obesity and cardiovascular risk: the new public health problem of worldwide
      proportions.
AB  - Obesity could be considered a new global health epidemic above all others,
      especially when it is characterized by central fat distribution. This is
      illustrated by dramatic provisional data, indicating a continuous increase in the
      trend of overweight and obese individuals in several countries, including the USA
      and countries in Europe. Several epidemiological, pathophysiological and clinical
      studies clearly indicate that two of the major independent risk factors for
      cardiovascular disease or events are being overweight, and obesity. Accordingly,
      weight loss and prevention of weight gain has to be considered one of the most
      important strategies to reduce the incidence of cardiovascular disease.

PMID- 15151471
TI  - Can endovascular therapy of infrainguinal disease for claudication be justified?
AB  - Traditionally, patients with exercise-induced lower extremity ischemia
      (claudicants) have been treated conservatively. It is important to remember that
      this is not because the pain of claudication is less important than pain due to
      other problems, but because the only 'cure', operative bypass, has been judged
      too invasive by both patient and physician. Recent data suggest that endovascular
      treatment of atherosclerotic disease below the inguinal ligament yields good
      short-term results, with low periprocedural morbidity and does not compromise
      future surgical alternatives in the long-term. If this approach is to be used as
      nonoperative treatment for the pain of claudication, however, the authors suggest
      that long-term success may be less important than the absolute minimization of
      short-term and periprocedural risk. The authors believe that given the results of
      modern endovascular therapy it is increasingly less acceptable to tell
      claudicants to live with their pain if conservative therapy fails. The option of
      endovascular treatment for infrainguinal atherosclerotic disease should be
      discussed with every patient whose claudication is significant, and considered as
      a treatment option in place of continued pain. This approach should be judged
      against conservative therapy for claudication, not against surgical bypass for
      limb threat.

PMID- 15151470
TI  - Treatment of metabolic syndrome.
AB  - The metabolic syndrome is intended to identify patients who have increased risk
      of diabetes and/or a cardiac event due to the deleterious effects of weight gain,
      sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol
      Education Program's Adult Treatment Panel III definition uses easily measured
      clinical findings of increased abdominal circumference, elevated triglycerides,
      low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or
      elevated blood pressure. Three of these five are required for diagnosis. The
      authors also note that other definitions of metabolic syndrome focus more on
      insulin resistance and its key role in this syndrome. This review focuses on how
      treatment might affect each of the five components. Abdominal obesity can be
      treated with a variety of lower calorie diets along with regular exercise.
      Indeed, all of the five components of the metabolic syndrome are improved by even
      modest amounts of weight loss achieved with diet and exercise. For those with
      impaired fasting glucose tolerance, there is good evidence that a high fiber, low
      saturated fat diet with increased daily exercise can reduce the incidence of
      diabetes by almost 60%. Of note, subjects who exercise the most, gain the most
      benefit. Metformin has also been shown to be helpful in these subjects.
      Thiazolidinedione drugs may prove useful, but further studies are needed.
      Although intensified therapeutic lifestyle change will help the abnormal lipid
      profile, some patients may require drug therapy. This review also discusses the
      use of statins, fibrates, and niacin. Likewise, while hypertension in the
      metabolic syndrome benefits from therapeutic lifestyle change, physicians should
      also consider angiotensin converting enzyme inhibitor drugs or angiotensin
      receptor blockers, due to their effects on preventing complications of diabetes,
      such as progression of diabetic nephropathy and due to their effects on
      regression of left ventricular hypertrophy. Aspirin should be considered in those
      with at least a 10% risk of a coronary event over 10 years. Finally, three
      related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome
      and protease inhibitor associated lipodystrophy improve with therapeutic
      lifestyle change. Although metformin is shown to be useful with polycystic ovary
      syndrome, the data supporting drug therapy for the other syndromes is less
      convincing. More robust studies are needed before any firm recommendations can be
      made.

PMID- 15151472
TI  - Minimally invasive valve surgery: different techniques and approaches.
AB  - Less invasive approaches to cardiac surgical procedures are being developed in an
      effort to decrease patient morbidity and enhance postoperative recovery in
      comparison with conventional methods. Although full median sternotomy has been
      the standard surgical approach to the heart for more than 30 years, minimally
      invasive techniques using limited incisions are rapidly gaining acceptance.
      Potential advantages of a small skin incision include less trauma and tissue
      injury, leading to a less painful and quicker overall recovery, as well as
      shorter hospital stays for patients. Decreasing the size of the skin incision for
      minimally invasive valve surgery to significantly less than the cardiac size
      requires specific access to the valve to be repaired or replaced. Thus, various
      minimally invasive techniques and approaches have been described for aortic and
      mitral valve surgery. This article will review the different minimally invasive
      techniques and approaches, as well as early results and outcomes for aortic and
      mitral valve surgery.

PMID- 15151473
TI  - Transcatheter closure of perimembranous ventricular septal defects.
AB  - The isolated perimembranous ventricular septal defect is one of the most common
      congenital cardiac malformations. Although surgery has been performed and has a
      low associated risk, it still involves morbidity due to factors such as residual
      leaks, atrioventricular block, postpericardiotomy syndrome and arrhythmias. It
      has been speculated that percutaneous closure of these defects could minimize
      such complications. Recently, a device designed specifically for perimembranous
      ventricular septal defect closure, the Amplatzer membranous ventricular septal
      defect occluder, has been developed. Initial clinical experience with this device
      has been very encouraging with results showing a high rate of complete closure
      and a low incidence of complications at mid-term follow-up. In this article, the
      authors review their own and others' experience with this device.

PMID- 15151474
TI  - Cardiovascular effects of selective cyclooxygenase-2 inhibitors.
AB  - Selective cyclooxygenase-2 inhibitors represent a significant advance in the
      management of inflammatory disorders. They have similar efficacy to nonselective
      'conventional' nonsteroidal anti-inflammatory drugs, but a superior
      gastrointestinal safety profile. However, a significant caveat is the perceived
      potential of cyclooxygenase-2 inhibitors to cause adverse cardiovascular effects,
      an issue first raised by the Vioxx Gastrointestinal Outcomes Research (VIGOR)
      study of rofecoxib (Vioxx, Merck & Co. Inc.). Mechanisms by which cyclooxygenase
      2 inhibitors may increase cardiovascular risk are selective inhibition of
      prostaglandin I2 over thromboxane A2 within the eicosanoid pathway, which
      promotes thrombosis, and inhibition of prostaglandins E2 and I2 within the
      kidney, which leads to sodium and water retention and blood pressure elevation.
      In spite of this, the cardiovascular findings from VIGOR are not firmly supported
      by observations from large cohort studies and other clinical trials of selective
      cyclooxygenase-2 inhibitors, including the Celecoxib Long-term Arthritis Safety
      Study. The two main theories that explain the VIGOR findings are that the
      comparator used (naproxen; Naprosyn, Roche) is cardioprotective and that very
      high doses of rofecoxib were used, but at present neither is backed by firm
      evidence. Indeed, there is now early evidence that selective cyclooxygenase-2
      inhibition with celecoxib may even protect against the progression of
      cardiovascular disease, on the basis that cyclooxygenase-2 mediates key processes
      in atherothrombosis. Currently, it is not clear what the net cardiovascular
      effects of cyclooxygenase-2 inhibitors are. The data are inconsistent and at
      best, speculative. It may be also that celecoxib and rofecoxib differ in their
      cardiovascular effects. Clarification of these issues is of vital importance
      given the vast number of patients presently taking both types of cyclooxygenase-2
      inhibitors. Therefore, what is clear in this situation is the urgent need for
      randomized clinical trials designed specifically to examine the impact of
      selective cyclooxygenase-2 inhibitors on cardiovascular risk.

PMID- 15151476
TI  - Intra-arterial thrombolysis in acute ischemic stroke: a review of pharmacologic
      approaches.
AB  - Ischemic stroke is a major public health problem worldwide. The potential to cure
      stroke patients with intravenous thrombolytic therapy has evolved to the use of
      intra-arterial thrombolytic agents. Fewer than 200 patients have been enrolled in
      randomized trials of intra-arterial therapy. In this article the authors have
      reviewed the literature listed in MEDLINE and EMBase, and searched relevant
      articles to examine the role of fibrinolytic agents in acute interventional
      stroke therapy. Only English language articles reporting five or more patients
      were included. Outcomes were defined at 90 days. Good outcome was defined on the
      modified Rankin Scale. Symtpomatic hemorrhage was defined as hemorrhage in the
      setting of clinical deterioration in the first 24 to 48 h. The search identified
      57 studies of which 44 reported usable data. Only three randomized trials were
      reported. Of a total of 1140 patients, most (73%) were treated open-label with
      urokinase (Abbokinase, Abbott Laboratories). The best outcomes were reported in
      case series and slightly worse outcomes were reported in clinical trials.
      Overall, it was not possible to distinguish whether one agent was superior to the
      others. There is a paucity of published evidence on intra-arterial therapy for
      acute ischemic stroke. Alteplase (Activase, Genentech Inc.) is currently the drug
      of choice simply because it is available and it is the current intravenous
      standard. Further trials and developments are anticipated.

PMID- 15151475
TI  - Therapeutic angiogenesis for myocardial ischemia.
AB  - Therapeutic angiogenesis offers promise as a novel treatment for ischemic heart
      disease, particularly for patients who are not candidates for current methods of
      revascularization. The goal of treatment is both relief of symptoms of coronary
      artery disease and improvement of cardiac function by increasing perfusion to the
      ischemic region. Protein-based therapy with cytokines including vascular
      endothelial growth factor and fibroblast growth factor demonstrated functionally
      significant angiogenesis in several animal models. However, clinical trials have
      yielded largely disappointing results. The attenuated angiogenic response seen in
      clinical trials of patients with coronary artery disease may be due to multiple
      factors including endothelial dysfunction, particularly in the context of
      advanced atherosclerotic disease and associated comorbid conditions, regimens of
      single agents, as well as inefficiencies of current delivery methods. Gene
      therapy has several advantages over protein therapy and recent advances in gene
      transfer techniques have improved the feasibility of this approach. The safety
      and tolerability of therapeutic angiogenesis by gene transfer has been
      demonstrated in phase I clinical trials. The utility of therapeutic angiogenesis
      by gene transfer as a treatment option for ischemic cardiovascular disease will
      be determined by adequately powered, randomized, placebo-controlled Phase II and
      III clinical trials. Cell-based therapies offer yet another approach to
      therapeutic angiogenesis. Although it is a promising therapeutic strategy,
      additional preclinical studies are warranted to determine the optimal cell type
      to be administered, as well as the optimal delivery method. It is likely the
      optimal treatment will involve multiple agents as angiogenesis is a complex
      process involving a large cascade of cytokines, as well as cells and
      extracellular matrix, and administration of a single factor may be insufficient.
      The promise of therapeutic angiogenesis as a novel treatment for no-option
      patients should be approached with cautious optimism as the field progresses.

PMID- 15151477
TI  - Rationale for aggressive lipid lowering: evidence from clinical trials.

PMID- 15151479
TI  - Eplerenone in the treatment of chronic heart failure.
AB  - There has been a recent revival of interest in aldosterone receptor antagonists
      for the treatment of chronic heart failure. This was largely triggered by fresh
      insights into the role of aldosterone in a number of key pathophysiological
      processes, including fibrosis and remodeling, inflammation, and the potentiation
      of catecholamine effects. The therapeutic efficacy of spironolactone (Aldactone),
      Pfizer) in severe chronic heart failure was established by the Randomized
      Aldactone Evaluation Study, but hormonal side effects (gynecomastia) associated
      with the drug posed a problem. More recently, the Eplerenone Post-Acute
      Myocardial Infarction Heart Failure Efficacy and Survival Study has provided firm
      support for the use of eplerenone (Inspra, Pfizer) in heart failure following
      acute myocardial infarction in addition to neurohormonal blockade with
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and
      beta-blockers. This strategy can be expected to benefit both mortality and
      morbidity. Due to the fact that eplerenone is a selective aldosterone receptor
      antagonist, it does not cause troublesome hormonal side effects. This is an
      important feature of the drug that is likely to help maintain compliance.

PMID- 15151480
TI  - Clinical application of enoxaparin.
AB  - Low-molecular-weight heparins have several important advantages over
      unfractionated heparin (UFH). Due to a longer plasma half life together with high
      bioavailability and a linear dose-response relationship, the drugs can be safely
      and effectively administered in the hospital or ambulatory settings without the
      need to monitor the anticoagulant effect. Enoxaparin (Lovenox), Aventis Pharma)
      is a low-molecular-weight heparin which has been studied in a variety of clinical
      situations. In general surgery the efficacy of enoxaparin to prevent venous
      thromboembolism is similar to UFH but the tolerability is better. In patients
      undergoing cancer, orthopedic or vascular surgery the efficacy of enoxaparin is
      significantly higher with similar rates of bleeding complications. The database
      for enoxaparin in nonsurgical patients is smaller compared with surgical groups.
      There is evidence that the efficacy of enoxaparin may be superior to UFH in
      patients with severe cardiac disease. Efficacy and safety of UFH and enoxaparin
      are similar for the treatment of deep vein thrombosis. However, enoxaparin can be
      safely administered by the patients at home which is not possible with UFH. In
      patients with acute coronary syndromes, enoxaparin has been shown to reduce the
      rate of deaths and serious cardiac events in comparison with UFH. Furthermore,
      exonaparin treatment has been shown to be cost-effective, and therefore is the
      therapy of choice in this setting. In addition, enoxaparin has been shown to be a
      safe and effective alternative to the combination of UFH and phenprocoumone
      therapy in patients undergoing electrical cardioversion for atrial fibrillation.

PMID- 15151481
TI  - Lepirudin: a bivalent direct thrombin inhibitor for anticoagulation therapy.
AB  - Lepirudin (Refludan), Berlex Laboratories, USA and Canada; Pharmion, all other
      countries), a recombinant derivative of the naturally occurring leech
      anticoagulant hirudin, was the first direct thrombin inhibitor to be approved by
      the European Agency for the Evaluation of Medicinal Products and the US Food and
      Drug Administration for the treatment of heparin-induced thrombocytopenia. Since
      its introduction into Europe and the USA, it has been studied in over 7000
      patients requiring anticoagulation in conditions including acute coronary
      syndromes, percutaneous coronary intervention, cardiopulmonary bypass and heparin
      induced thrombocytopenia. Three European clinical trials, designated Heparin
      Associated Thrombocytopenia (HAT)-1, -2 and -3, demonstrated the efficacy and
      safety of lepirudin in the prevention and treatment of thrombosis in patients
      with antibody-confirmed heparin-induced thrombocytopenia. A postmarketing,
      observational study, termed the Drug-Monitoring Program, evaluated lepirudin in
      over 1000 patients with heparin-induced thrombocytopenia in the setting of
      routine clinical practice. In the Drug-Monitoring Program, adverse events were
      substantially reduced compared with clinical trials, while clinical efficacy was
      maintained; suggesting that insight gained through clinical experience was
      translated into improved safety. Here, pharmacotherapy using lepirudin is
      reviewed, with particular reference to clinical studies in heparin-induced
      thrombocytopenia, and some recommendations based on this extensive clinical
      experience with lepirudin are provided. Although only approved for the treatment
      of heparin-induced thrombocytopenia, the use of lepirudin in acute coronary
      syndromes, percutaneous coronary intervention, vascular surgery and coronary
      artery bypass grafting is also discussed. The review concludes with a discussion
      of pharmacokinetic and clinical data supporting the potential for subcutaneous
      administration of lepirudin.

PMID- 15151483
TI  - Hypertension and left ventricular hypertrophy in autosomal dominant polycystic
      kidney disease.
AB  - Hypertension is a common problem in patients with autosomal dominant polycystic
      kidney disease affecting both renal and patient survival. Activation of the renin
      angiotensin-aldosterone system due to cyst expansion and local renal ischemia has
      been proposed to play an important role in the development of hypertension in
      autosomal dominant polycystic kidney disease. Left ventricular hypertrophy, a
      major cardiovascular risk factor, is also common in patients with autosomal
      dominant polycystic kidney disease. Both hypertension and the activation of the
      renin-angiotensin-aldosterone system play a role in the development of left
      ventricular hypertrophy in these patients. Prospective randomized results
      indicate that aggressive control of blood pressure is important for the optimal
      reversal of left ventricular hypertrophy, thereby diminishing a major risk factor
      for cardiovascular morbidity and mortality of patients with autosomal dominant
      polycystic kidney disease. There is also substantial epidemiological support for
      aggressive control of blood pressure in slowing renal disease progression in
      autosomal dominant polycystic kidney disease patients. Blockade of the renin
      angiotensin-aldosterone system should be the initial approach in the treatment of
      hypertension in these patients.

PMID- 15151482
TI  - New European, American and International guidelines for hypertension management:
      agreement and disagreement.
AB  - Hypertension is a leading cause of morbidity and mortality worldwide and its
      control rates remain poor. In 2003, several official organizations presented new
      guidelines for hypertension management. These guidelines were developed using an
      evidence-based interpretation of the available information. Recommendations on
      hypertension prevention, diagnosis, patients' evaluation, decision to treat,
      antihypertensive drug selection and goals of treatment are included. There is
      considerable agreement among the new guidelines and only a few points of
      disagreement, that are of minor significance. Emphasis has been placed on the
      simplicity of recommendations in order for them to be easily applied by primary
      care physicians. This review focuses on the key messages of the 2003 guidelines
      and the areas of agreement and disagreement among them.

PMID- 15151484
TI  - Prognostic value of ambulatory blood pressure measurements for the diagnosis of
      hypertension in pregnancy.
AB  - Several studies have indicated that the use of the 24 h mean blood pressure,
      mainly using reference thresholds derived from general nonpregnancy practice,
      does not provide an effective test for an individualized early diagnosis of
      hypertension in pregnancy, thus concluding that ambulatory blood pressure
      monitoring is not a valid approach in pregnancy. With the use of ambulatory blood
      pressure monitoring, epidemiologic studies have reported gender differences in
      the circadian variability of blood pressure and heart rate. Typically, men
      exhibit a lower heart rate and higher blood pressure than women, the differences
      being larger for systolic than for diastolic blood pressure. Moreover,
      normotensive and hypertensive pregnant women are characterized by differing but
      predictable patterns of blood pressure variability throughout gestation. However,
      the diminished blood pressure in nongravid women as compared with men, the added
      decrease in blood pressure during the second trimester of gestation in
      normotensive but not in hypertensive pregnant women and the large amplitude of
      the circadian pattern that characterizes the blood pressure of healthy pregnant
      women at all gestational ages, have not been taken into account when establishing
      reference thresholds for the diagnosis of hypertension in pregnancy. This review
      will describe these issues, summarize previous results from independent groups on
      the prognostic value of ambulatory blood pressure monitoring in pregnancy,
      propose answers as to an accurate reference threshold for blood pressure at
      different stages of gestation and suggest how this information should be used in
      order to identify those women at a higher risk of hypertension, who will also be
      more suitable for prophylactic and/or therapeutic intervention in the early
      stages of pregnancy.

PMID- 15151485
TI  - Pharmacology of orthostatic hypotension in Parkinson's disease: from
      pathophysiology to management.
AB  - Orthostatic hypotension is highly prevalent in the elderly, and affects up to 20%
      of patients with Parkinson's disease. Pharmacological approaches help to
      demonstrate that Parkinson's disease is a primary autonomic failure with
      involvement of the peripheral autonomic nervous system as shown by decreased
      [(123)I] meta-iodobenzylguanidine cardiac uptake and preserved growth hormone
      response to clonidine. No specific clinical trial has evaluated efficacy of
      antihypotensive drugs in Parkinson's disease. End point of treatment should be a
      reduction in postural symptoms. Midodrine (Proamatin), Roberts Pharmaceutical), a
      vasoconstrictor and fludrocortisone (Florinef), Bristol-Myers Squibb), a volume
      expander are first choice drugs. No data are available on their effects on
      orthostatic hypotension-related morbidity. The usefulness of other drugs remains
      to be demonstrated. This review will highlight the importance of
      nonpharmacological measures in the management of orthostatic hypotension in
      Parkinson's disease.

PMID- 15151486
TI  - Hypolipidemic treatment of heterozygous familial hypercholesterolemia: a lifelong
      challenge.
AB  - In familial hypercholesterolemia, a defect in low-density lipoprotein receptors
      causes lifelong two- to threefold elevations in serum low-density lipoprotein
      cholesterol levels. This leads to early atherosclerotic changes in infancy.
      Lifelong hypolipidemic treatment that can be started at a young age is thus
      greatly needed. Early diagnosis of familial hypercholesterolemia is important,
      and improved DNA tests for low-density lipoprotein receptor mutations have made
      it possible to carry out diagnosis at birth. A low saturated-fat, low cholesterol
      diet can be safely started at 7 months of age. This can be accompanied by dietary
      stanol esters from 2 years of age. At the age of 10, statin treatment can be
      safely started. In adults, more aggressive hypolipidemic treatment is required in
      order to reach the treatment goal for serum low-density lipoprotein-cholesterol
      levels less than 2.5 mmol/l. This can be achieved by using high doses of statin,
      or preferably by combining a statin with resin or ezetimibe (Zeita), Merck and
      Shering-Plough Pharmaceuticals). Once started, treatment of familial
      hypercholesterolemia is lifelong.

PMID- 15151487
TI  - High-density lipoproteins: multifunctional vanguards of the cardiovascular
      system.
AB  - The plasma level of high-density lipoprotein (HDL)-cholesterol is inversely
      correlated with coronary artery disease, the leading cause of death worldwide.
      HDL particles are thought to mediate the uptake of peripheral cholesterol and,
      through exchange of core lipids with other lipoproteins or selective uptake by
      specific receptors, return this cholesterol to the liver for bile acid secretion
      or hormone synthesis in steroidogenic tissues. HDL particles also act on vascular
      processes by modulating vasomotor function, thrombosis, cell-adhesion molecule
      expression, platelet function, nitric oxide release, endothelial cell apoptosis
      and proliferation. Many of these effects involve signal transduction pathways and
      gene transcription. Several genetic disorders of HDLs have been characterized at
      the molecular level. The study of naturally occurring mutations has considerably
      enhanced understanding of the role of HDL particles. Some mutations causing HDL
      deficiency are associated with premature coronary artery disease, while others,
      paradoxically, may be associated with longevity. Modulation of HDL metabolism for
      therapeutic purposes must take into account, not only the cholesterol content of
      a particle but its lipid (especially phospholipid) composition, apolipoprotein
      content, size and charge. Current therapeutic strategies include the use of
      peroxisome proliferating activator receptor-alpha agonists (fibrates) that
      increase apolipoprotein AI production and increase lipoprotein lipase activity,
      statins that have a small effect on HDL-cholesterol but markedly reduce low
      density lipoprotein-cholesterol, the cholesterol/HDL-cholesterol ratio and niacin
      that increases HDL-cholesterol. Potential therapeutic targets include inhibition
      of cholesteryl ester transfer protein, modulating the ATP-binding cassette A1
      transporter, and decreasing HDL uptake by scavenger receptor-B1. Novel therapies
      include injection of purified apolipoprotien AI and short peptides taken orally,
      mimicking some of the biological effects of apolipoprotein AI.

PMID- 15151488
TI  - Achieving lipid goals in Europe: how large is the treatment gap?
AB  - Despite the established benefits of decreasing low-density lipoprotein
      cholesterol levels in reducing morbidity and mortality from coronary heart
      disease, not all patients who would benefit from lipid-lowering therapy are being
      managed appropriately. An in-depth review of the literature (2000-2003)
      demonstrates that the 'treatment gap' varies across different clinical settings.
      Although the use of lipid-lowering agents has increased in recent years, there
      continues to be a widespread failure in the achievement of recommended lipid
      levels. A combination of the use of the most efficacious statins, together with
      intervention strategies to ensure that all eligible individuals receive
      appropriate treatment to achieve lipid goals, are important considerations in
      minimizing the burden of dyslipidemia in Europe.

PMID- 15151489
TI  - Complementary research paradigms.

PMID- 15151490
TI  - Active cycle of breathing techniques in non-invasive ventilation for acute
      hypercapnic respiratory failure.
AB  - We hypothesised that applying the active cycle of breathing techniques (ACBT) in
      patients with acute hypercapnic respiratory failure undergoing non-invasive
      ventilation would improve patient outcome. Thirty-four patients were randomised
      so that 17 patients with acute hypercapnic respiratory failure received the ACBT
      and non-invasive ventilation (ACBT group), and 17 patients received non-invasive
      ventilation alone (control group). The primary outcome measure was length of time
      requiring non-invasive ventilation, and secondary outcome measures were change in
      acute physiology score, change in arterial blood gas values, total duration of
      non-invasive ventilation, and length of stay in the intensive care unit. Although
      not significant, there was a greater decrease in arterial carbon dioxide pressure
      in the ACBT group compared to the control group (-21.41 mmHg vs -17.45 mmHg, p =
      0.27). Total duration of ventilation tended to be shorter in the ACBT group than
      in the control group (64.9 hours vs 84.1 hours, p = 0.15). Length of time in need
      of non-invasive ventilation was significantly lower in the ACBT group than in the
      control group (5.0 days vs 6.7 days, p = 0.03). There was no significant
      difference in length of stay in the intensive care unit between the two groups
      (8.0 vs 9.4 days, p = 0.31). The use of ACBT may have positive effects in the
      treatment of patients with acute hypercapnic respiratory failure, resulting in a
      shorter length of time requiring non-invasive ventilation.

PMID- 15151491
TI  - A randomised clinical trial evaluating the efficacy of physiotherapy after
      rotator cuff repair.
AB  - The optimal form of rehabilitation after rotator cuff repair has yet to be
      determined. A randomised clinical trial was undertaken to compare outcomes for
      two forms of rehabilitation for this condition: individualised supervised
      physiotherapy treatment, and a standardised unsupervised home exercise regime.
      Fifty-eight volunteers with all sizes of operatively repaired rotator cuff tears
      were allocated randomly to one of the two treatment groups. All subjects received
      a standardised home exercise regime. Subjects who were randomised to the
      physiotherapy group received additional individualised treatment. Independent,
      blinded assessments of range of motion, muscle force and functional outcome
      measures were performed pre-operatively, and at six, 12 and 24 weeks
      postoperation. At six, 12 and 24 weeks post-operation, comparable outcomes were
      demonstrated for both rehabilitation groups. By 24 weeks post-operation, most
      subjects demonstrated outcomes that were consistent with a favourable recovery,
      regardless of rehabilitation mode. On the basis of these results, outcomes for
      subjects allocated to individualised physiotherapy treatment after rotator cuff
      repair are no better than for subjects allocated to a standardised home exercise
      regime.

PMID- 15151492
TI  - Inter-tester reliability of a new diagnostic classification system for patients
      with non-specific low back pain.
AB  - Most patients referred to physiotherapy with low back pain are without a precise
      medical diagnosis. Identification of subgroups of non-specific low back pain
      patients may improve clinical outcomes and research efficiency. A pathoanatomic
      classification system has been developed, classifying patients with non-specific
      low back pain into 12 different syndromes and three subcategories based on
      history and physical examination. The purpose of this study was to estimate the
      inter-tester reliability of clinical tests used as criteria for classifying
      patients. Ninety patients with chronic low back pain were each examined by two
      physiotherapists. A total of four physiotherapists conducted the assessments.
      Examination findings were recorded independently by the two examiners. Percentage
      of agreement and kappa coefficients were calculated for each category. The
      overall rate of agreement was 72% and the kappa coefficient was 0.62 for the
      mutually exclusive syndromes in the classification system. Agreement rates for
      each of the syndromes ranged from 74% to 100% and kappa coefficients ranged from
      0.44 to 1.00. The findings suggest the inter-tester reliability of the system is
      acceptable. The relatively modest level of total agreement (39%) for the system
      as a whole might indicate that the utility of the system for general screening
      purposes is limited, compared with the utility in identification of particular
      syndromes. Due to low prevalence of positive findings in some of the syndromes,
      future work should focus on testing reliability on a larger sample of patients,
      and testing of validity and feasibility of the system.

PMID- 15151493
TI  - Physiological responses to the early mobilisation of the intubated, ventilated
      abdominal surgery patient.
AB  - The aim of this study was to investigate the effects of mobilisation on
      respiratory and haemodynamic variables in the intubated, ventilated abdominal
      surgical patient. Mobilisation was defined as the progression of activity from
      supine, to sitting over the edge of the bed, standing, walking on the spot for
      one minute, sitting out of bed initially, and sitting out of bed for 20 minutes.
      Seventeen patients with age (mean +/- SD) 71.4 +/- 7.1 years satisfied inclusion
      criteria. Respiratory and haemodynamic parameters were measured in each of the
      above positions and compared with supine. In the 15 subjects who completed the
      protocol, standing resulted in significant increases in minute ventilation (VE)
      from 15.1 +/- 3.1 l/min in supine to 21.3 +/- 3.6 l/min in standing (p < 0.001).
      The increase in VE in standing was achieved by significant increases in tidal
      volume (VT) from 712.7 +/- 172.8 ml to 883.4 +/- 196.3 ml (p = 0.008) and in
      respiratory rate (fR) from 21.4 +/- 5.0 breaths/min to 24.9 +/- 4.5 breaths/min
      (p = 0.03). No further increases were observed in these parameters beyond
      standing when activity was progressed to walking on the spot for one minute. When
      supine values were compared with walking on the spot for one minute, inspiratory
      flow rates (VT/TI) increased significantly from 683 +/- 131.8 ml/sec to 985.1 +/-
      162.3 ml/sec (p = 0.001) with significant increases in rib cage displacement (p =
      0.001) and no significant increase in abdominal displacement (p = 0.23). Arterial
      blood gases displayed no improvements following mobilisation. Changes in VT, fR,
      and VE were largely due to positional changes when moving from supine to
      standing.

PMID- 15151494
TI  - Australian physiotherapists and mandatory notification of child abuse:
      legislation and practice.
AB  - Child abuse is an international phenomenon occurring in all socioeconomic groups.
      Reports of child abuse continue to increase and many professionals are likely to
      see abused children and may be the first contact for an abused child. In
      addition, many health professionals and others are mandated in some Australian
      states to report suspected child abuse. However, the literature addressing the
      roles of Australian health professionals in child protection is limited. This
      paper informs Australian physiotherapists about child protection legislation,
      types of abuse, suspicion on reasonable grounds, and responding to a situation of
      suspected child abuse.

PMID- 15151495
TI  - Use of anti-pronation taping to assess suitability of orthotic prescription: case
      report.
AB  - This case report describes a strategy for assessing the suitability of orthotic
      prescription for individual patients with lower limb overuse injuries. The case
      concerns a 32 year old male soccer player with a two-year history of Achilles
      tendinopathy. A functional assessment performed before, during, and after a trial
      period of anti-pronation taping showed that taping reduced symptoms markedly and
      resulted in a 10-fold increase in pain-free jogging distance. This was
      interpreted as an indication for favourable orthotic intervention. Subsequently,
      orthotic intervention was associated with a similar reduction in symptoms and
      improvement in function. This case study illustrates how a trial period of anti
      pronation taping could assist therapists to make decisions about prescription of
      orthoses for lower limb overuse injuries.

PMID- 15151496
TI  - Pathophysiology of acute lung injury in combined burn and smoke inhalation
      injury.
AB  - In the U.S.A., more than 1 million burn injuries occur every year. Although the
      survival from burn injury has increased in recent years with the development of
      effective fluid resuscitation management and early surgical excision of burned
      tissue, the mortality of burn injury is still high. In these fire victims,
      progressive pulmonary failure and cardiovascular dysfunction are important
      determinants of morbidity and mortality. The morbidity and mortality increases
      when burn injury is associated with smoke inhalation. In the present review, we
      will describe the pathophysiological aspects of acute lung injury induced by
      combined burn and smoke inhalation and examine various therapeutic approaches.

PMID- 15151497
TI  - Development of an individual-specific autoantibody (ISA) protein microarray.
AB  - We have developed an ISA (individual-specific autoantibody) identification method
      to identify biological samples based on an individual's unique class of
      autoantibodies. This method involved the presentation of human proteins derived
      from crude lysates after SDS/PAGE separation and transferance to a solid support.
      In the present study, ISA strips are produced and developed on a new protein
      microarray. In making the ISA strips, it was found that variation in protein
      migration during electrophoresis and strip-manufacturing quality control limit
      the reliability of the assay. Therefore it was decided to semi-purify and
      separate proteins by column chromatography in large batches and to develop an ISA
      specific protein microarray. It was found that this ISA protein microarray
      approximates a similar serum titre as the ISA strip and is predicted to
      circumvent the batch-to-batch production issues related to SDS/PAGE.

PMID- 15151498
TI  - Incidental neurodevelopmental episodes in the etiology of schizophrenia: an
      expanded model involving epigenetics and development.
AB  - Epidemiological data favors genetic predisposition for schizophrenia, a common
      and complex mental disorder in most populations. Search for the genes involved
      using candidate genes, positional cloning, and chromosomal aberrations including
      triplet repeat expansions have established a number of susceptibility loci and
      genomic sites but no causal gene(s) with a proven mechanism of action. Recent
      genome-wide gene expression studies on brains from schizophrenia patients and
      their matched controls have identified a number of genes that show an alteration
      in expression in the diseased brains. Although it is not possible to offer a
      cause and effect association between altered gene expression and disease, such
      observations support a neurodevelopmental model in schizophrenia. Here, we offer
      a mechanism of this disease, which takes into account the role of developmental
      noise and diversions of the neural system. It suggests that the final outcome of
      a neural developmental process is not fixed and exact. Rather it develops with a
      variation around the mean. More important, the phenotypic consequence may cross
      the norm as a result of fortuitous and/or epigenetic events. As a result, a
      normal genotype may develop as abnormal with a disease phenotype. More important,
      susceptible genotypes may have reduced penetrance and develop as a normal
      phenocopy. The incidental episodes in neurodevelopment will explain the frequency
      of schizophrenia in most populations and high discordance of monozygotic twins.

PMID- 15151499
TI  - Breaking symmetry: a clinical overview of left-right patterning.
AB  - It is increasingly recognized that mutations in genes and pathways critical for
      left-right (L-R) patterning are involved in common isolated congenital
      malformations such as congenital heart disease, biliary tract anomalies, renal
      polycystic disease, and malrotation of the intestine, indicating that disorders
      of L-R development are far more common than a 1 in 10,000 incidence of
      heterotaxia might suggest. Understanding L-R patterning disorders requires
      knowledge of molecular biology, embryology, pediatrics, and internal medicine and
      is relevant to day-to-day clinical genetics practice. We have reviewed data from
      mammalian (human and mouse) L-R patterning disorders to provide a clinically
      oriented perspective that might afford the clinician or researcher additional
      insights into this diagnostically challenging area.

PMID- 15151504
TI  - Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome
      families.
AB  - Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder
      characterized by early onset diabetes mellitus and progressive optic atrophy.
      Patients with WS frequently develop deafness, diabetes insipidus, renal tract
      abnormalities, and diverse psychiatric illnesses, among others. A gene
      responsible for WS was identified on 4p16.1 (WFS1). It encodes a putative 890
      amino acid transmembrane protein present in a wide spectrum of tissues. A new
      locus for WS has been located on 4q22-24, providing evidence for the genetic
      heterogeneity of this syndrome. Six Spanish families with a total of seven WS
      patients were screened for mutations in the WFS1-coding region by direct
      sequencing. We found three previously undescribed mutations c.873C > A,
      c.1949_50delAT, and c.2206G > C, as well as the duplication c.409_424dup16,
      formerly published as 425ins16. Several groups had detected deletions in the
      mitochondrial DNA (mtDNA) of WS patients. For this reason, we also studied the
      presence of mtDNA rearrangements as well as Leber's hereditary optic neuropathy,
      mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and
      A1555G point mutations in the WS families. No mtDNA abnormalities were detected.

PMID- 15151505
TI  - Genetic effect of two polymorphisms in the apolipoprotein A5 gene and
      apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese
      population.
AB  - Two polymorphisms, apolipoprotein A5 (APOA5) -1131T>C and apolipoprotein C3
      (APOC3) -482C>T, were examined in a healthy Chinese group. Analysis of covariance
      (ancova) showed that both -1131T>C and -482C>T minor alleles were associated with
      triglyceride (TG)-raising effects (p < 0.001 and p = 0.012, respectively) after
      adjustment of sex, age, and body mass index (BMI). Moreover, -1131T>C minor
      alleles were also found to be associated with total cholesterol (TC)-raising
      effects (p = 0.045). However, the relationship between -482C>T minor alleles and
      TC-raising effects was not observed after adjustment of sex, age, and BMI. By
      contrast, significant inverse associations were noted between minor alleles (
      1131T>C and -482C>T) and high-density lipoprotein cholesterol (HDL-C)
      concentrations (p = 0.021 and p = 0.021, respectively). Linear regression
      analysis showed that the effects of -1131T>C and -482C>T polymorphisms on TG and
      HDL-C (0.001 and 0.008; 0.041 and 0.005, respectively) are independent and
      additive and that -1131T>C can seriously affect the levels of TG (0.001 vs
      0.008). The additive effect of the two polymorphisms was confirmed further by
      haplotype analysis. Our results strongly support that the two single nucleotide
      polymorphisms, -1131T>C in APOA5 and -482C>T in APOC3, are related to the levels
      of serum TG and HDL-C and those of other several lipids and lipoproteins in the
      Chinese population.

PMID- 15151506
TI  - Prader-Willi syndrome resulting from an unbalanced translocation:
      characterization by array comparative genomic hybridization.
AB  - Prader-Willi syndrome (PWS) is caused by lack of expression of paternally
      inherited genes on chromosome 15q11-->15q13. Most cases result from
      microdeletions in proximal chromosome 15q. The remainder results from maternal
      uniparental disomy of chromosome 15, imprinting center defects, and rarely from
      balanced or unbalanced chromosome rearrangements involving chromosome 15. We
      report a patient with multiple congenital anomalies, including craniofacial
      dysmorphology, microcephaly, bilateral cryptorchidism, and developmental delay.
      Cytogenetic analysis showed a de novo 45,XY,der(5)t(5;15)(p15.2;q13), -15
      karyotype. In effect, the proband had monosomies of 5p15.2-->pter and 15pter-
      >15q13. Methylation polymerase chain reaction analysis of the promoter region of
      the SNRPN gene showed only the maternal allele, consistent with the PWS
      phenotype. The proband's expanded phenotype was similar to other patients who
      have PWS as a result of unbalanced translocations and likely reflects the
      contribution of the associated monosomy. Array comparative genomic hybridization
      (array CGH) confirmed deletions of both distal 5p and proximal 15q and provided
      more accurate information as to the size of the deletions and the molecular
      breakpoints. This case illustrates the utility of array CGH in characterizing
      complex constitutional structural chromosome abnormalities at the molecular
      level.

PMID- 15151507
TI  - Single nucleotide polymorphism in CTH associated with variation in plasma
      homocysteine concentration.
AB  - Plasma total homocysteine (tHcy) concentration, an independent risk factor of
      atherosclerosis, has numerous genetic and environmental determinants. While the
      thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase
      is the best-studied genetic factor associated with variation in plasma tHCy,
      other candidate genes are being evaluated. Recently, we discovered that
      cystathioninuria was caused by mutations in the CTH gene encoding cystathionine
      gamma-lyase, an enzyme that converts cystathionine to cysteine in the trans
      sulfuration pathway. We also identified a common single nucleotide polymorphism
      (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we
      studied the association of genotypes of this SNP with plasma tHcy concentrations
      in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean
      plasma tHcy concentration than subjects with other genotypes, and the effect
      sizes of CTH and MTHFR genotypes were similar. The findings suggest that common
      variation in CTH may be a determinant of plasma tHcy concentrations.

PMID- 15151508
TI  - Mutation spectrum of the glucose-6-phosphatase gene and its implication in
      molecular diagnosis of Korean patients with glycogen storage disease type Ia.
AB  - Glycogen storage disease type Ia (GSD Ia; MIM 232200) is an autosomal recessive
      inherited metabolic disorder resulting from a deficiency of the microsomal
      glucose-6-phosphatase (G6Pase), the enzyme that catalyzes the terminal step in
      gluconeogenesis and glycogenolysis. Various mutations in the G6Pase gene (G6PC)
      have been found in patients with GSD Ia. To elucidate the spectrum of the G6PC
      gene mutations, 13 unrelated Korean patients with GSD Ia were analyzed. We were
      able to identify mutant alleles in all patients, including three known mutations
      (727G > T, G122D, and T255I) and two novel mutations (P178A and Y128X). The
      frequency of the 727G > T mutation in Korean patients with GSD Ia was 81%
      (21/26), which was slightly lower than that (86-92%) in Japanese but much higher
      than that (44.4%) in Taiwan Chinese. Except one, all patients were either
      homozygous (9/13) or compound heterozygous (3/13) for the 727G > T mutation; the
      only patient without the 727G > T mutation was a compound heterozygote for the
      G122D and Y128X mutations. Our findings suggest that a DNA-based test can be used
      as the initial diagnostic approach in Korean patients clinically suspected to
      have GSD Ia, thereby avoiding invasive liver biopsy.

PMID- 15151509
TI  - Bronchiectasis in adult patients: an expression of heterozygosity for CFTR gene
      mutations?
AB  - While all patients with cystic fibrosis (CF) have mutations in both CFTR alleles,
      often only one CFTR change is detected in patients with other lung disorders. The
      aim of this study was to investigate whether heterozygosity for CFTR mutations
      could be a determinant risk factor in the development of bronchiectasis in adult
      patients. We have performed the CFTR gene analysis in a cohort of 55
      bronchiectasis adult patients with unknown etiology. The 5T variant (TG)m and the
      M470V polymorphisms were also analyzed. A general population in which the same
      molecular analysis was previously performed was used as the control group. The
      mutational spectrum of patients was also compared with that found in our CF
      population. CFTR mutations/variants were found in 20 patients (36%), 14 with only
      one mutant gene (25%). All six patients colonized by Staphylococcus aureus
      presented with at least one CFTR change (p = 0.001). No statistical significance
      was observed between patients with and without mutations for other clinical
      features. The 5T variant was found in four patients. Additionally, 90% of
      patients with mutations had the more functional M470 allele (p < 0.001). These
      results suggest the involvement of the CFTR gene in bronchiectasis of unknown
      etiology in adult patients.

PMID- 15151511
TI  - The fronto-ocular syndrome: second mother-daughter case.

PMID- 15151510
TI  - Candidate genes for recessive non-syndromic mental retardation on chromosome 3p
      (MRT2A).
AB  - A mild type of autosomal recessive, non-syndromic mental retardation (NSMR) is
      linked to loci on chromosome 3p. This report delimits the MRT2A minimal critical
      region to 4.2 Mb between loci D3S3630 and D3S1304. This interval contains nine
      genes (IL5RA, TRNT1, LRRN1, SETMAR, SUMF1, ITPR1, BHLHB2, EDEM, and MRPS36P1).
      The results suggest that a mutation does not exist in these genes and that an
      unknown transcript in the region contributes to the cognitive deficits in NSMR.

PMID- 15151512
TI  - ARX mutation in a boy with transsphenoidal encephalocele and hypopituitarism.

PMID- 15151513
TI  - The frequency of GJB2 mutations and the Delta (GJB6-D13S1830) deletion as a cause
      of autosomal recessive non-syndromic deafness in the Kurdish population.

PMID- 15151515
TI  - The revision of the Declaration of Helsinki: past, present and future.
AB  - The World Medical Association's Declaration of Helsinki was first adopted in
      1964. In its 40-year lifetime the Declaration has been revised five times and has
      risen to a position of prominence as a guiding statement of ethical principles
      for doctors involved in medical research. The most recent revision, however, has
      resulted in considerable controversy, particularly in the area of the ethical
      requirements surrounding placebo-controlled trials and the question of
      responsibilities to research participants at the end of a study. This review
      considers the past versions of the Declaration of Helsinki and asks the question:
      How exactly has the text of the Declaration changed throughout its lifetime?
      Regarding the present form of the Declaration of Helsinki we ask: What are the
      major changes in the most recent revision and what are the controversies
      surrounding them? Finally, building on the detailed review of the past and
      present versions of the Declaration of Helsinki, we give consideration to some of
      the possible future trajectories for the Declaration in the light of its history
      and standing in the world of the ethics of medical research.

PMID- 15151516
TI  - Effects of single or combined histamine H1-receptor and leukotriene CysLT1
      receptor antagonism on nasal adenosine monophosphate challenge in persistent
      allergic rhinitis.
AB  - BACKGROUND: The effects of single or combined histamine H(1)-receptor and
      leukotriene CysLT(1)-receptor antagonism on nasal adenosine monophosphate (AMP)
      challenge in allergic rhinitis are unknown. OBJECTIVE: We elected to study the
      effects of usual clinically recommended doses of fexofenadine (FEX), montelukast
      (ML) and FEX + ML combination, compared with placebo (PL), on nasal AMP challenge
      in patients with persistent allergic rhinitis. METHODS: Twelve patients with
      persistent allergic rhinitis (all skin prick positive to house dust mite) were
      randomized in a double-blind cross-over fashion to receive for 1 week either FEX
      180 mg, ML 10 mg, FEX 180 mg + ML 10 mg combination, or PL, with nasal AMP
      challenge performed 12 h after dosing. There was a 1-week washout period between
      each randomized treatment. The primary outcome measure was the maximum percentage
      peak nasal inspiratory flow (PNIF) fall from baseline over a 60-min period after
      nasal challenge with a single 400 mg ml(-1) dose of AMP. The area under the 60
      min time-response curve (AUC) and nasal symptoms were measured as secondary
      outcomes. RESULTS: There was significant attenuation (P < 0.05) of the mean
      maximum percentage PNIF fall from baseline after nasal AMP challenge vs. PL, 48;
      with FEX, 37; 95% confidence interval for difference 2, 20; ML, 35 (4, 22); and
      FEX + ML, 32 (7, 24). The AUC (%.min) was also significantly attenuated (P <
      0.05) vs. PL, 1893; with FEX, 1306 (30, 1143); ML, 1246 (214, 1078); and FEX +
      ML, 1153 (251, 1227). There were no significant differences for FEX vs. ML vs.
      FEX + ML comparing either the maximum or AUC response. The total nasal symptom
      score (out of 12) was also significantly improved (P < 0.05) vs. PL, 3.3; with
      FEX, 2.1 (0.3, 2.0); ML, 2.0 (0.5, 1.9); and FEX + ML, 2.5 (0.1, 1.4).
      CONCLUSION: FEX and ML as monotherapy significantly attenuated the response to
      nasal AMP challenge and improved nasal symptoms compared with PL, while
      combination therapy conferred no additional benefit.

PMID- 15151517
TI  - Endothelins and their inhibition in the human skin microcirculation: ET[1-31], a
      new vasoconstrictor peptide.
AB  - AIMS: Endothelin-1 (ET-1([1-21])) is an extremely potent vasoconstrictor in the
      human skin microcirculation and is generated from larger precursor peptides. The
      aims of the present study were to assess the vasoactive effects of these
      precursors as well as endothelin blockade in the human skin microcirculation, in
      vivo. METHODS: Six healthy volunteers received intradermal injections of a range
      of doses of big ET-1([1-38]), ET-1([1-31]), ET-1([1-21]), BQ-123 (ET(A) receptor
      antagonist), BQ-788 (ET(B) receptor antagonist), phosphoramidon [endothelin
      converting enzyme (ECE) inhibitor] or saline control (0.9%). Skin blood flow
      (SBF) was measured using standard laser Doppler flowmetry. RESULTS: Big ET-1([1
      38]), ET-1([1-31]) and ET-1([1-21]) reduced SBF when compared with saline control
      (P < 0.01 for all). Big ET-1([1-38]) and ET-1([1-31]) were less potent than ET
      1([1-21]) as defined by skin vasoconstriction. Phosphoramidon, BQ-123 and BQ-788,
      given alone, all caused vasodilatation in the human skin microcirculation (P <
      0.01 for all). CONCLUSIONS: In the human skin microcirculation, big ET-1([1-38])
      and ET-1([1-31]) are less potent vasoconstrictors than ET-1([1-21]). The effects
      of big ET-1([1-38]) and phosphoramidon suggest the presence of endogenous ECE
      activity in the skin. In contrast to skeletal muscle resistance vessels, ET-1([1
      21]) contributes to the maintenance of skin microvascular tone through both ET(A)
      and ET(B) receptor-mediated vasoconstriction.

PMID- 15151518
TI  - The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized
      calcium concentrations in patients with chronic renal failure on haemodialysis
      both on the day of haemodialysis and on the day without haemodialysis.
AB  - AIMS: Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH)
      in patients with secondary hyperparathyroidism; however, hypercalcaemia,
      hyperphosphataemia, or both, often develop. Calcimimetic agents, employed in
      alternative therapeutic approaches, directly inhibit PTH secretion by activating
      the calcium-sensing receptor in the parathyroid glands. METHODS: In this study,
      patients were given orally 25, 50, and 100 mg doses of the calcimimetic agent KRN
      1493 each on two occasions, on the day of haemodialysis and on the day without
      haemodialysis. RESULTS: In the pharmacokinetic results, because the clearance of
      KRN 1493 by haemodialysis was much smaller than the systemic clearance, the
      influence of haemodialysis was not remarkable. In the pharmacodynamic study, on
      both the days with or without haemodialysis, plasma PTH concentrations decreased
      in a dose-dependent manner. Serum calcium concentrations decreased in association
      with the decrease in plasma PTH concentrations. Mild dose-dependent adverse
      effects (mainly nausea) were seen after the administration of KRN 1493 on both
      the day of haemodialysis and the day without haemodialysis. CONCLUSIONS: We
      conclude that the pharmacokinetics of KRN 1493 after a single administration were
      similar on the day of haemodialysis and the day without haemodialysis. KRN 1493
      is safe and effective in suppressing PTH secretion and serum calcium
      concentrations on the day of haemodialysis and on the day without haemodialysis
      in patients with secondary hyperparathyroidism.

PMID- 15151519
TI  - Population pharmacokinetics of pyrimethamine and sulfadoxine in children with
      congenital toxoplasmosis.
AB  - AIMS: To develop a population pharmacokinetic model for pyrimethamine (PYR) and
      sulfadoxine (SDX) in children with congenital toxoplasmosis. METHODS: Children
      were treated with PYR (1.25 mg kg(-1)) and SDX (25 mg kg(-1)) (Fansidar) plus
      folinic acid (Lederfoline) 5 mg). Plasma concentrations, available from a
      therapeutic drug monitoring database, were determined by high-performance liquid
      chromatography. Population pharmacokinetic analysis was performed using a
      nonlinear mixed effects model. RESULTS: Eighty-nine children, aged 1 week to 14
      years and weighing 2.9-59 kg, were available for evaluation. Both PYR and SDX
      concentration-time profiles were best described by a one-compartment open model.
      Volume of plasma distribution (V) and clearance (CL) were significantly related
      to body weight (BW) using an allometric function. Typical CL and V estimates (95%
      confidence interval), for a child weighing 11 kg were 5.50 (5.28, 5.73) l day(-1)
      and 36 (33, 39) l for PYR and 0.26 (0.25, 0.27) l day(-1) and 2.1 (1.9, 2.3) l
      for SDX. For BW between 3.5 and 60 kg, plasma half-lives were predicted to vary
      from 4.0 to 5.2 days for PYR, and from 5.0 to 7.5 days for SDX. CONCLUSION: This
      study indicated that body weight influences PYR and SDX pharmacokinetics in
      children. To optimize PYR/SDX combination treatment in congenital toxoplasmosis,
      short dosing intervals in very young low-wight children are probably appropriate.

PMID- 15151521
TI  - Population pharmacokinetics of total and unbound plasma cisplatin in adult
      patients.
AB  - AIMS: To investigate the pharmacokinetics of unbound (ultrafilterable) and total
      plasma platinum using a population approach and to identify patient
      characteristics that may influence the disposition of the drug. METHODS:
      Pharmacokinetic and demographic data were collected from adult patients treated
      with 30-min daily infusions of cisplatin for various malignancies. Unbound and
      total platinum concentration-time data were analysed using a nonlinear mixed
      effects model. RESULTS: Data from 43 patients were available for analysis. A
      linear two-compartment model best described total and unbound platinum plasma
      concentration-time data. The mean population estimates for total and unbound drug
      were, respectively, 0.68 and 35.5 l h(-1) for clearance and 21.1 and 23.4 l for
      central distribution volume (V(1)). Unbound clearance (CL) was dependent on body
      surface area (BSA) and creatinine clearance, and V(1) was dependent on BSA. The
      elimination rate constant for plasma-bound platinum (modelled as metabolite
      formation) was 0.014 h(-1). The pharmacokinetic parameter, f(m)/V(m), a measure
      of the clearance of unbound platinum due to irreversible plasma binding, was
      related to serum protein concentration and to the inverse of dose per m(2). The
      covariate modelling of CL, V(1) and f(m)/V(m) improved the intersubject
      variabilities associated with these parameters. The final pharmacokinetic models
      were validated using 200 bootstrap samples from the original datasets.
      CONCLUSIONS: The results support the conventional dose adjustment of cisplatin
      based on BSA. They also support the need for a dose reduction in case of renal
      insufficiency.

PMID- 15151520
TI  - Population pharmacokinetics of (R)-, (S)- and rac-methadone in methadone
      maintenance patients.
AB  - AIM: To construct a population pharmacokinetic model for methadone enantiomers in
      the setting of methadone maintenance treatment for opioid dependence. METHODS: A
      population pharmacokinetic model was developed using P-Pharm software for rac-,
      (R)- and (S)-methadone using data (8-13 plasma samples per subject) obtained from
      59 methadone maintenance patients during one interdosing interval at steady
      state. The patients were randomly assigned to either a development (n = 38) or a
      validation dataset (n = 21). The model was refined by inclusion of all subjects
      to construct a final basic model, which was used to construct a covariate model.
      RESULTS: A population-based two-compartment open model with first-order
      absorption and lag time was developed and validated for all analytes. The
      population geometric mean (coefficient of variation) of maximum a posteriori
      probability Bayesian estimated values for clearance, terminal half-life and
      volume of distribution at steady-state of the active (R)-enantiomer were 8.7
      (42%) l h(-1), 51 (45%) h and 597 (45%) l, respectively. For all analytes, the
      volume of the central compartment was decreased with increasing plasma alpha(1)
      acid glycoprotein concentration and was lower in females, while the delay in
      absorption was longer at higher doses. No covariates were identified for apparent
      oral clearance. The apparent oral clearance of (R)-methadone (geometric mean
      ratio; 95% confidence interval) was 105% (99, 110), that of (S)-methadone (P =
      0.19), while (R)-methadone V(c)/F (154%; 151, 157), V(dss) /F (173%; 164, 183),
      t(1/2beta) (162%; 153, 172) and mean residence time (166%; 156, 176) were
      significantly greater (P < 0.0001) than for (S)-methadone. The population
      pharmacokinetic models were able to predict accurately oral clearance values from
      limited (one or two samples) blood sampling protocols. CONCLUSIONS: The
      substantial stereoselectivity in methadone disposition reinforces the potential
      for misinterpretation of racemic methadone disposition data. The marked
      interindividual variability in (R)-methadone clearance, with no covariates
      identified, highlights the need for alternative methods to determine an
      individual's metabolic clearance. The ability to predict (R)-methadone clearance
      from one to two blood samples at steady state may prove clinically useful if a
      drug-drug interaction or poor adherence are suspected and guide the prescriber in
      deciding if a client's request for a dose increase is warranted or whether an
      alternative opioid would be more appropriate.

PMID- 15151522
TI  - Maximum a posteriori Bayesian estimation of epirubicin clearance by limited
      sampling.
AB  - AIMS: To develop a limited sampling strategy for estimation of epirubicin
      clearance. METHODS: The data set comprised 1051 concentrations measured in 105
      patients with advanced or metastatic breast cancer treated with epirubicin alone.
      Ten limited sampling designs comprising two or three blood samples were proposed,
      taken at times identified by D-optimality from population pharmacokinetic
      parameter estimates. The data set was then truncated to include the sampling
      times for each of the designs. MAP Bayesian estimates of clearance were generated
      for each design and compared with clearance estimates obtained using all the
      data. The limited sampling designs were also validated using a separate data set
      obtained from 18 patients with either breast cancer or hepatocellular carcinoma.
      The sensitivity of the best limited sampling designs to sample time recording
      errors of 0-10% or 10-20% was then assessed using a simulated data set including
      200 patients. RESULTS: The optimum sampling times were: end of the injection and
      18 min, 40 min, 3 h, 10 h and 48 h after the start of the injection. The best
      three-sample design included samples at 40 min, 3 h and 48 h and gave unbiased
      estimates of clearance with an imprecision of 9.1% (95% CI 7.3, 10.5). The best
      two sample design included samples at 3 and 48 h and gave unbiased estimates of
      clearance with an imprecision of 12.4% (95% CI 9.6, 14.6). Using the validation
      data set, these two and three sample designs gave unbiased estimates of clearance
      with an imprecision of 5.6% (95% CI 3.7, 7.0) and 4.2% (95% CI 2.6, 5.3),
      respectively. Simulations that included 0-10% or 10-20% errors in the recording
      of the blood sampling times had negligible effects on the bias and imprecision of
      clearance estimates. CONCLUSIONS: Limited sampling designs have been identified
      and validated that estimate epirubicin clearance with adequate precision and
      without bias from two or three blood samples. These designs also allow
      flexibility in blood sample collection and are robust with regard to sample time
      recording errors.

PMID- 15151523
TI  - The effects of renal impairment on the pharmacokinetics and safety of
      fosfluconazole and fluconazole following a single intravenous bolus injection of
      fosfluconazole.
AB  - AIMS: Fosfluconazole is a phosphate prodrug of fluconazole (FLCZ). This study was
      conducted to investigate the effect of renal impairment on the pharmacokinetics
      of fosfluconazole and FLCZ, and to assess the safety and toleration of
      fosfluconazole following a single intravenous bolus injection of fosfluconazole
      in subjects with normal and impaired renal function. METHODS: In an open,
      parallel-group, two-centre study, subjects with normal and impaired renal
      function received a single 1000-mg bolus intravenous injection of fosfluconazole.
      Subjects were categorized as Normal (> 80 ml min(-1)), Mild (51-80 ml min(-1)),
      Moderate (30-50 ml min(-1)) or Severe (< 30 ml min(-1)) impairment group
      according to their Cockcroft and Gault creatinine clearance (CLcr) values.
      Concentrations of fosfluconazole and FLCZ were determined in plasma and urine
      samples taken up to 240 h and 48 h postdose, respectively. RESULTS:
      Fosfluconazole plasma concentrations were very similar across the four groups,
      and there was no apparent relationship between any of the fosfluconazole
      pharmacokinetic parameters with increasing renal impairment. The conversion of
      fosfluconazole to FLCZ was unaffected by the degree of renal impairment. Only
      small amounts of fosfluconazole were excreted in the urine suggesting almost
      complete conversion to FLCZ. FLCZ concentrations were still detected in plasma
      after 240 h postdose and remained higher at the later sampling times in subjects
      in the Moderate and Severe groups. The area under the plasma concentration vs.
      time curve between time zero and infinity (AUC), the terminal elimination phase
      half-life (t(1/2)) and the mean residence time (MRT) of FLCZ all increased with
      the degree of renal impairment. The ratios (95% confidence interval) for AUC
      (Renal impairment group/Normal group) were 112.8% (89.5, 142.1), 240.6% (128.2,
      451.4) and 355.1% (259.3, 486.3) for the Mild, Moderate and Severe impairment
      groups, respectively. There was a linear relationship between CLcr with AUC,
      t(1/2), MRT and the total plasma clearance of FLCZ (CL/F). Both the amount
      excreted over 48 h in the urine and the renal clearance of FLCZ decreased with an
      increase in renal impairment. The adverse events reported were mild to moderate
      in intensity, and there was no observed relationship with impairment group. There
      were no severe or serious adverse events, and in general fosfluconazole was well
      tolerated. CONCLUSIONS: The pharmacokinetics of fosfluconazole, including its
      efficient conversion into FLCZ, were unaffected by renal impairment. For FLCZ,
      there was a significant linear relationship between CLcr and AUC, t(1/2), MRT and
      CL/F, with AUC, t(1/2) and MRT increasing and CL/F decreasing as renal impairment
      increased. The dose adjustment used for FLCZ (half normal dose for patients with
      CLcr at <or= 50 ml min(-1)) can be applied to fosfluconazole as well. There were
      no safety concerns for any subject in this study, and fosfluconazole and FLCZ
      were well tolerated by all the treatment groups.

PMID- 15151524
TI  - Relationship between Type A and B personality and debrisoquine hydroxylation
      capacity.
AB  - AIM: A person with Type A personality is an 'aggressor' compared with the rarely
      harried Type B. Although debrisoquine hydroxylase (CYP2D6) capacity has been
      associated with personality, no study has specifically investigated its
      association with personality Type A and B. Therefore the aim of this research was
      to study the impact of CYP2D6 on Type A and B personality. METHODS: Type A and B
      personality questionnaires were administered to 48 healthy patients undergoing
      elective orthopaedic surgery. After obtaining informed consent, patients were
      genotyped for the various CYP2D6 alleles by allele-specific polymerase chain
      reaction. Based on the genotypes, patients were grouped as extensive metabolizer
      (EM)1 (normal) (CYP2D6*1/*1), EM2 (intermediate) (CYP2D6*1/*4, CYP2D6*1/*5,
      CYP2D6*1/*9 and CYP2D6*1/*10) and EM3 (slow) (CYP2D6*4/*10, CYP2D6*5/*10,
      CYP2D6*10/*10 and CYP2D6*10/*17). Chi(2) was used to determine the relationship
      between the groups and personality types. RESULTS: The percentages of patients
      who were of the EM1, EM2 and EM3 groups were 20.8%, 52.1% and 27.1%,
      respectively. There was a significant difference (P = 0.032) between the three
      groups in terms of personality type, in which EM1 showed a tendency to be of
      personality Type A while EM2 and EM3 tended to be of personality Type B.
      CONCLUSION: The study suggests that there is a relationship between CYP2D6
      activity and Type A and B personality.

PMID- 15151525
TI  - Leflunomide in active rheumatoid arthritis: a prospective study in daily
      practice.
AB  - AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions
      and withdrawal from leflunomide in an outpatient population with rheumatoid
      arthritis in a setting of care-as-usual. METHODS: In this prospective case series
      study, from outpatient medical records a standard dataset was collected including
      patient and disease characteristics, data on leflunomide use and adverse drug
      reactions. RESULTS: During the study period 136 rheumatoid arthritis patients
      started leflunomide. Median (range) follow-up duration was 317 (11-911) days.
      Sixty-five percent of patients experienced at least one adverse drug reaction
      related to leflunomide. During follow-up 76 patients (56%) withdrew from
      leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of
      efficacy (13%). The overall incidence density for withdrawal from leflunomide was
      56.2 per 100 patient-years. Complete data for calculating efficacy using a
      validated disease activity score on 28 joints (DAS(28)) was available for 48, 36,
      and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12
      month period after start of leflunomide treatment 76% of the evaluable patients
      were classified as moderate or good responders according to the DAS(28) response
      criteria. CONCLUSIONS: In the setting of care-as-usual, rheumatoid arthritis
      patients starting leflunomide frequently experienced adverse drug reactions. More
      than half of the patients withdrew from leflunomide treatment within a year after
      start of leflunomide treatment, mainly because of adverse drug reactions.

PMID- 15151526
TI  - Stroke prevention and atrial fibrillation: reasons leading to an inappropriate
      management. Main results of the SAFE II study.
AB  - AIMS: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was
      to identify the reasons underlying the under-utilization of oral anticoagulation
      (OAC) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We
      investigated from all available sources the reasons why patients hospitalized for
      a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We
      interviewed general practitioners (GPs) and cardiologists with a structured
      questionnaire, to identify the reasons for their therapeutic choice. RESULTS: Of
      370 patients, 257 were theoretically eligible for OAC according to guidelines and
      the presence of contra-indications, but only 82 (22.2%) of them had actually
      received OAC before. We found that factors independently associated with the
      prescription of OAC were being followed-up by a cardiologist and having a younger
      GP. The leading reason evoked by GPs or cardiologists to explain why patients
      were not treated with OAC was the presence of a 'potential contra-indication',
      which was often inappropriate, followed by 'there was no indication', 'low
      compliance' and 'fear of bleeding'. CONCLUSIONS: An important reason for not
      prescribing OAC was the lack of knowledge about trials and guidelines. Medical
      education about OAC in NVAF should therefore be improved.

PMID- 15151528
TI  - Bisphosphonate use and subsequent prescription of acid suppressants.
AB  - AIM: To determine the extent of prescribing of acid suppression agents associated
      with initiation of bisphosphonate therapy. METHODS: This was a case control
      study, performed within the General Practice Network, Australia. The main outcome
      measure was re-attendance within six weeks from index bisphosphonate prescription
      for acid supression agents. RESULTS: Of the bisphosphonate cases, 2.9%[95%
      confidence interval (CI) 1.8, 3.9] returned within 6 weeks for a prescription for
      proton pump inhibitor, histamine 2 receptor antagonist or antacid, compared with
      0.9% of control patients (95% CI 0.5, 1.2). However, the bisphosphonate cases had
      significantly higher rates of previous use of nonsteroidal anti-inflammatory
      agents. After controlling for previous nonsteroidal anti-inflammatory drug use,
      the increased use of acid suppression agents was statistically significant, the
      odds ratio = 3.21 (95% CI 2.02, 5.11). CONCLUSION: Bisphosphonate use appears to
      be associated with increased use of acid suppressant agents within 6 weeks of
      first supply.

PMID- 15151527
TI  - Subclinical alteration of taste sensitivity induced by candesartan in healthy
      subjects.
AB  - AIMS: There have been case reports of taste disturbance for the angiotensin II
      receptor blockers losartan and valsartan, but not for candesartan. This study was
      undertaken to examine whether candesartan causes taste disturbance. METHODS:
      Candesartan cilexetil (4 mg day(-1)) or vehicle was given to healthy volunteers
      (n = 8) for 7 days in a randomized, double-blind, placebo-controlled, cross-over
      design with a 2-week washout period. Clinical gustometry using the filter-paper
      disc test and electrogustometry were sequentially performed before and at the end
      of each trial. Serum and salivary zinc concentrations were also measured.
      RESULTS: Detection thresholds of four basic tastes (sweet, salty, sour and
      bitter) determined by the paper disc test were significantly (P < 0.05 in all
      tests) worsened (i.e. score of test increased) after repeated dosing of the drug,
      although the subjects did not notice such changes. The mean +/- SEM (and 95% CI)
      scores of the four tastes at just before the seventh dosing of candesartan or
      vehicle was 3.38 +/- 0.32 (3.02, 3.74) and 2.63 +/- 0.18 (2.18, 3.08) for
      sweetness, 3.63 +/- 0.38 (4.49, 2.77) and 2.63 +/- 0.26 (3.27, 1.98) for salt,
      4.01 +/- 0.42 (3.04, 4.98) and 2.61 +/- 0.32 (3.35, 1.87) for sourness, 4.01 +/-
      0.38 (3.22, 4.80) and 2.99 +/- 0.33 (2.24, 3.74) for bitterness, for candesartan
      and placebo, respectively. Electrogustometry confirmed the candesartan-related
      taste disturbance. Serum and salivary zinc concentrations were not influenced by
      candesartan. CONCLUSIONS: These data suggest that candesartan subclinically
      reduces taste sensitivity after repeated dosing in healthy subjects. Because
      similar events are reported for losartan and valsartan in case reports, this
      adverse effect might be a class effect of angiotensin-II receptor blockers
      (ARBs).

PMID- 15151533
TI  - 12th Symposium of the Association of European Psychiatrists Section on
      Epidemiology and Social Psychiatry. 23-26 June, 2004, Mannheim, Germany.
      Abstracts.

PMID- 15151529
TI  - Quinine intoxications: a continuing problem.

PMID- 15151539
TI  - Relation between predischarge auditory brainstem responses and clinical factors
      in high-risk infants.
AB  - BACKGROUND: Advances in perinatal medicine have increased the survival rate of
      infants admitted to neonatal intensive care units (NICU). Some of the infants
      will have health problems including hearing disorder and/or brainstem
      dysfunction, and may have associated communicative and cognitive difficulties
      and/or repeated apnea attacks that require therapy or care. METHODS: In this
      study, the authors measured mean thresholds and mean I-V interpeak latencies in
      56 high-risk infants and 30 controls who were about to be discharged from NICU.
      The authors retrospectively investigated whether predischarge auditory brainstem
      response (ABR) data, which seem to be related to a number of clinical factors
      affecting neonates, are useful for detecting hearing disorder and/or brainstem
      dysfunction, and we investigated six clinical factors. RESULTS: The results
      showed that the positive risk factors for hearing impairment in infants who are
      about to be discharged from the NICU are: receiving mechanical ventilation
      (including for a period of <1 day) and the administration of five or more
      different antibiotics, especially in extremely low-birthweight (ELBW) infants.
      Another result showed that the high-risk mature infants had a significant high
      risk factor for brainstem dysfunction. CONCLUSIONS: The findings of the study
      emphasize the importance of performing ABR examinations in high-risk infants,
      even in infants who are about to be discharged from an NICU. ABR examinations are
      especially important in ELBW infants or mature infants who have received
      mechanical ventilation or who have received five or more different antibiotics.

PMID- 15151540
TI  - Population attributable fraction of smoking to low birth weight in Japan.
AB  - BACKGROUND: The purpose of this study is to quantify the population attributable
      fraction of active and passive smoking for low birth weight in Japan. METHODS: A
      population-based case-control study was conducted by mailing self-report
      questionnaires. The cases were all singleton low birth weight babies who were
      born between 1 January 1998 and 30 June 1999 in Tochigi prefecture, Japan. The
      controls were randomly selected from all singleton babies who were born during
      the same period as cases in the prefecture. RESULTS: The number of cases and
      controls were 286 and 404, respectively. Population attributable fractions of
      active smoking during and before pregnancy were 7.0% and 8.8%, respectively.
      Population attributable fraction of passive smoking at home was 15.6% and at the
      workplace was 1.1%. Combined population attributable fraction of both active and
      passive smoking was 17.3%. CONCLUSION: Public education to eliminate passive
      smoking for pregnant women and smoking prevention in adolescence is very
      important in order to reduce the risk of low birth weight.

PMID- 15151541
TI  - Significance of hypocarbia in the development of periventricular leukomalacia in
      preterm infants.
AB  - BACKGROUND: Despite rapid advances in the management of preterm infants,
      periventricular leukomalacia (PVL) remains a considerable problem in neonatal
      intensive care. The aim of this study was to determine whether hypocarbia is
      associated with the development of PVL in mechanically ventilated, preterm
      infants and to emphasize the importance of avoiding this disturbance. METHODS:
      The authors evaluated 52 mechanically ventilated infants with a gestational age
      of <34 weeks, who exhibited hypocarbia in the first three postnatal days (lowest
      carbon dioxide tension being <25 mmHg). These infants were then compared with 52
      infants in a control group not exhibiting hypocarbia, matched for birthweight and
      gestational age. A diagnosis of PVL was made on the basis of the results of
      cranial ultrasonography. Confounding factors potentially associated with the
      development of PVL were controlled in logistic regression analyses. RESULTS: Of
      the 52 mechanically ventilated preterm infants with hypocarbia, 10 (19.2%)
      developed cystic PVL, and six (11.5%) developed periventricular echodensity. Of
      the 52 infants in the control group only two (3.8%) developed cystic PVL, and one
      (1.9%) infant developed periventricular echodensity. The authors observed no
      significant differences in other prenatal and perinatal risk factors between the
      two groups. CONCLUSION: Hypocarbia in mechanically ventilated preterm infants
      during the first days of life is suggested as being an independent predictor of
      PVL, predisposing these infants to subsequent neurodevelopmental delay.

PMID- 15151542
TI  - Ineffective erythropoiesis underlies the clinical heterogeneity of congenital
      dyserythropoietic anemia type II (CDA II).
AB  - BACKGROUND: Congenital dyserythropoietic anemia type II (CDA II) is an autosomal
      recessive disease, and is the most common CDA. The qualitative and quantitative
      defects of erythropoiesis in CDA II, as estimated by the hematological and
      biochemical parameters at the time of diagnosis, may not reflect the
      heterogeneity of the disease course of each patient. METHODS: Three pediatric
      patients with CDA II are herein presented, having an heterogeneous clinical
      course. In addition to bone marrow morphology, Ham test and SDS-PAGE of
      erythrocyte membrane protein, the present study also examined erythroid marrow
      activity, by measuring serum Erythropoietin (Epo), soluble Transferrin Receptors
      (sTfR) concentrations and Reticulocyte Production Index (RPI). RESULTS: All
      patients demonstrated the same pattern of ineffective erythropoiesis, having
      increased Epo (350-389 IU/L), sTfR concentrations (6.2-7.8 mg/L) and low RPI
      values (0.8-1.3). Erythron expansion was expressed by RPI values nearly twofold
      higher than normal values in parallel to raised sTfR and high Epo production.
      Despite the same degree of ineffective erythropoiesis seen in all patients, the
      severity of the clinical course was diverse in terms of frequency and clinical
      relevance of transfusion needs. CONCLUSION: An analysis of the parameters
      expressing ineffective erythropoiesis in CDA II can provide a better
      understanding of the degree of dyserythropoiesis, however it is not useful for
      predicting the clinical course of disease in patients, because the underlying
      genetic heterogeneity of this disorder remains obscure.

PMID- 15151543
TI  - Natural immunity to Haemophilus influenzae type B in children of Ankara, Turkey.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) infection has a high morbidity
      and mortality rate especially in children under 5 years of age. The incidence of
      Hib disease in Turkey is not known, and Hib vaccine is not included in the
      National Immunization Program. The aim of this study was to determine the natural
      immunity to Hib of children 6-60 months of age living in the Park Health Center
      region of Ankara, Turkey. METHODS: A total of 270 children were selected by
      layered random sampling method, and 242 of them (89.6%) participated in the
      study. A questionnaire was given to the parents of the children who were included
      in the study and blood samples were taken from those children. Anti-Hib IgG
      antibody (anti-PRP) level was determined in the serum by using anti-Haemophilus
      influenzae IgG EIA kit and anti-PRP antibody levels of 0.15 microg/mL and over
      were accepted as the natural immunity. RESULTS: Natural immunity was determined
      in 65.3% of the children. A relationship was determined statistically between the
      history of disease with possible Hib agent and with natural immunity.
      CONCLUSIONS: The exposure rate of children with Hib was higher than expected,
      even in children who were just a few months old. Our data revealed that
      multicentric, national studies should be done to define the burden of Hib disease
      before making a decision for Hib vaccine to be included in the National
      Immunization Program.

PMID- 15151544
TI  - A questionnaire survey on the use of quick-acting insulin analog in Japanese
      children and adolescents with type 1 diabetes.
AB  - BACKGROUND: The aim of this study was to investigate the actual condition of
      quick-acting insulin analog (Q) in Japanese children and adolescents with type 1
      diabetes. METHODS: Forty-seven physicians who managed 944 patients under 18 years
      of age with type 1 diabetes, were requested to complete questionnaires in May
      2002 regarding the use of Q. RESULTS: Q was administered to 417 out of 944 (44%)
      patients. The details of the daily insulin regimens were as follows: three doses
      of Q with basal insulin in 116 of 403 (29%), three doses of Q with more than
      twice the basal insulin in 69 of 403 (17%), and other modifications using either
      Q or regular insulin (R) depending on the patients' lifestyles in 213 of 403
      (53%). Q dose was equal to R after the change of insulin regimens in 232 of 290
      (80%). After switching to Q from R, the basal insulin dosage increased in 113 of
      341 (33%) and the number of basal insulin injections increased in 42 of 341
      (12%). After the transfer to Q from R, glycemic control was judged to improve in
      179 of 372 (48%), to have no significant change in 162 of 372 (44%), and to
      aggravate in 31 of 372 (8%). The majority of patients, (305/389; 78%), noted an
      improvement of quality of life (QOL) following the administration of Q.
      CONCLUSIONS: Q was considered to be useful in flexibility of daily insulin
      therapy and improvement of QOL in children and adolescents with type 1 diabetes.
      Insulin therapy for type 1 diabetes during childhood and adolescence should be
      tailored to meet individual needs.

PMID- 15151545
TI  - Changes in thyroid function after bone marrow transplant in young patients.
AB  - BACKGROUND: Changes in thyroid function among young patients who received bone
      marrow transplantation (BMT) were evaluated. METHODS: The study included 91
      patients (50 males) who underwent BMT from 1985 to 1995 at the age of 0.6-21
      years. Sixty patients had neoplastic disease such as leukemia or lymphoma, and
      the remainder had non-neoplastic diseases. Preconditioning regimen for BMT
      included 12 Gy of fractionated-total body irradiation (TBI) for patients with
      neoplastic disease and 3-8 Gy of irradiation for the remaining patients, in
      addition to chemotherapy. Evaluation of thyroid function was performed by serial
      assessment of basal serum FT4, FT3, TSH concentrations as well as by TRH test.
      RESULTS: No patient had overt hypothyroidism or elevated basal TSH concentrations
      (>10 mU/L). However, 6 (7%) of patients experienced exaggerated peak TSH response
      to TRH stimulation several years after BMT. In 33 patients whose thyroid status
      was evaluated before, within 3 months, and 1 year after BMT, serum FT3
      concentrations as well as peak TSH response to TRH stimulation significantly
      decreased immediately after BMT (<3 months) and normalized within 1 year.
      However, serum FT4 concentrations did not change significantly. One patient
      developed primary hypothyroidism and another developed follicular adenoma of the
      thyroid 5 and 12 years after BMT, respectively. CONCLUSION: Short-term changes in
      thyroid function after BMT can indicate euthyroid sick syndrome rather than
      tertiary hypothyroidism. It must be noted that overt hypothyroidism may occur
      several years after BMT, hence long-term follow-up of thyroid function is
      warranted.

PMID- 15151546
TI  - Is obesity a risk factor for psychopathology among adolescents?
AB  - BACKGROUND: Although several studies have documented the existence of
      psychopathology in obese adolescents, disagreement remains regarding the extent
      and nature of this psychopathology. The aim of the present study was to explore
      the type and frequency of psychopathology in a clinical as well as a non-clinical
      sample of obese adolescents, and in a normal weight control group. METHODS: The
      study sample consisted of a clinical study group of 30 obese adolescents, a non
      clinical obese group of 30 obese adolescents, and a control group of 30 normal
      weight adolescents. Psychological assessment was performed using a non-structured
      psychiatric interview, the Child Behavior Checklist (CBCL), Children Depression
      Inventory (CDI), Rosenberg Self-esteem scale (SES) and the Eating Attitude Test
      (EAT). RESULTS: More than half of the clinical obese adolescents (16/30) had a
      DSM-IV diagnosis, often involving major depressive disorder (n = 10). The mean
      scores of anxiety-depression, social problems, social withdrawal and total
      problem in the CBCL scale of the clinical obese group were significantly higher
      than the non-clinical obese group and the normal weight control group. The mean
      total scores of the SES and the CDI of the clinical obese group were higher than
      the normal weight control group. The mean total score of EAT of the clinical
      obese group was significantly higher than the normal weight control group, and
      the mean score of EAT of the non-clinical obese group was significantly higher
      than the normal weight control group. CONCLUSIONS: The results support previously
      published reports which show a higher ratio of psychopathology (depression,
      behavioral problems, low-esteem) among clinical obese adolescents than among non
      clinical obese adolescents. Findings provided evidence for a psychosocial at-risk
      population in a subgroup of obese adolescents.

PMID- 15151547
TI  - Analysis of factors that influence body mass index from ages 3 to 6 years: A
      study based on the Toyama cohort study.
AB  - BACKGROUND: The aim of the present study was to elucidate both environmental and
      behavioral factors that influence body mass index (BMI, kg/m2) among Japanese
      children from ages 3-6. METHODS: In 1992 (at age 3) and 1995 (at age 6), 8170 6
      year-old children (4176 boys and 3994 girls) were surveyed using a questionnaire
      on both body build (height and weight) and lifestyle. The correlation between BMI
      for 3-year-olds and for 6-year-olds were analyzed. From the temporal changes of
      body build between age 3 and 6 years, we categorized children into four groups:
      group 1, normal at both age 3 years and 6 years (normal/normal); group 2,
      overweight at age 3 years and normal at age 6 years (overweight/normal); group 3,
      normal at age 3 years and overweight at age 6 years (normal/overweight); and
      group 4, overweight at both age 3 years and 6 years (overweight/overweight). The
      authors compared the four groups with each other according to sex, concerning
      frequencies of children who matched the categories of environmental and
      behavioral factors. Each factor was tested using the chi2 test. Overweight
      children were defined as those whose BMI value was age-sex specific in the 90th
      percentile or more. RESULTS: A significant correlation was found between body
      builds for children aged 3 and 6 years in both genders (boys, r = 0.559, P <
      0.01; girls, r = 0.584, P < 0.01). Significant factors associated with overweight
      children were diet (eating rice, green tea, eggs, meat, but less breads and
      juice), rapid eating, short sleep duration, early bedtime, long periods of
      television viewing, avoidance of physical activity, and frequent bowel movement.
      DISCUSSION: Temporal changes in BMI from age 3 years to 6 years are significantly
      associated with both environmental and behavioral factors at age 6 years. The
      results of this study may be useful for health promotion programs designed to
      prevent obesity during the early stages of childhood.

PMID- 15151548
TI  - Stable seroprevalence of Helicobacter pylori infection in children during 1989
      1999 in Taipei, Taiwan.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is thought to be acquired in
      childhood. The present study aimed to examine the changing seroepidemiology of H.
      pylori in children in the same area of Taipei city during 1989-1999, and to try
      to elucidate the possible transmission route of H. pylori in children by
      comparing hepatitis A virus (HAV) seroprevalence in Taipei during the same
      decade. METHODS: Sera were collected from the apparently healthy children (965
      males and 835 females, aged 0-20 years) from the Chung Cheng District of Taipei
      city. H. pylori infection status was checked by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: In 1999, the overall prevalence rate of H. pylori infection was
      14.8% with no gender difference (P = 0.115). Children aged 1-3 years had the
      lowest prevalence rate (2.8%). The prevalence rate then increased steadily after
      3 years of age. The annual infection rate was 1.25% after 3 years of age and the
      seroprevalence rate was 21.5% at 15-18 years. In comparison with the previous H.
      pylori seroepidemiology study performed at the same district of Taipei city one
      decade ago, there is no significant cohort effect in H. pylori prevalence in
      Taipei children during the past decade (Odds ratio = 1.13; 95% confidence
      interval: 0.74-1.72). The epidemiological pattern between H. pylori and HAV was
      found to be different. CONCLUSION: The seroprevalence of H. pylori in children
      did not change significantly in the past decade. This epidemiological feature is
      different from HAV. The authors propose that there are other transmission routes
      of H. pylori than fecal-oral.

PMID- 15151549
TI  - Water and electrolyte absorption from hypotonic oral rehydration solution in rat
      small intestine and colon.
AB  - BACKGROUND: The authors evaluated and compared the efficacy of hypotonic oral
      rehydration solutions (ORS), isotonic ion solutions, and distilled water to
      elucidate the relation between net water absorption and osmolality, or between
      electrolyte absorption and their ion concentrations in rat small intestine and
      colon. METHODS: Water and electrolyte absorption from two hypotonic ORS (Solita-T
      granules No. 2 [STG2]; sodium 60 mEq/L, osmolality 249 mOsm/L, Solita-T granules
      No. 3 [STG3]; sodium 35 mEq/L, osmolality 199 mOsm/L), two isotonic ion solutions
      (Aqualight [AL]; sodium 30 mEq/L, osmolality 290 mOsm/L, Pocarisweat [PS]; sodium
      21 mEq/L, osmolality 300 mOsm/L), and distilled water, were evaluated by an in
      vivo perfusion technique with the small intestine and colon of anesthetized rats.
      RESULTS: In the small intestine and colon, two hypotonic ORS significantly
      promoted net water absorption much greater than did two isotonic ion solutions (P
      < 0.05). Net sodium absorption from two hypotonic ORS was significantly greater
      than that from two isotonic ion solutions (P < 0.05). Sodium absorption from all
      solutions was greater in the colon than in the small intestine. Distilled water
      did not contribute to give net water absorption in the small intestine, but in
      the colon, it caused almost equivalent net water absorption to that by two
      hypotonic ORS. The largest amount of sodium secretion from the small intestine
      and colon was induced by distilled water. CONCLUSIONS: These data indicate that
      low osmolality is a crucial factor to facilitate water absorption, and the
      electrolytes, sodium and chloride, can effectively be salvaged in the colon.

PMID- 15151550
TI  - Ceftriaxone-associated biliary sludge and pseudocholelithiasis during childhood:
      a prospective study.
AB  - BACKGROUND: Cholelithiasis is a rare condition seen during childhood. The aim of
      this study was to determine frequency of biliary sludge and cholelithiasis with
      ceftriaxone therapy. METHODS: Thirty-eight children aged between 1 month and 17
      years were evaluated with ultrasonographic examination at the initiation of the
      ceftriaxone therapy and 10th day of therapy, consecutively. If biliary sludge or
      cholelithiasis were demonstrated, scans were repeated monthly until pathology
      disappeared. RESULTS: Abnormal gallbladder sonograms were demonstrated in 36.8%
      (n = 14) of patients at the 10th day of therapy. Cholelithiasis was detected in
      28.9% (n = 11) of patients and biliary sludge was detected in 7.9% (n = 3). Two
      children still had cholelithiasis at the 30th day after therapy and one had
      cholelithiasis after the 60th day. The 9-year-old girl who still had
      cholelithiasis after 60 days of therapy also had nausea, vomiting and abdominal
      pain at 7 days after cessation of therapy. Her 90th day sonographic examination
      was normal. CONCLUSION: Reversible biliary sludge or pseudocholelithiasis due to
      ceftriaxone treatment is not a rare condition. Therefore it is benign,
      spontaneously resolved and clinical signs are usually absent.

PMID- 15151551
TI  - Clinical spectrum of acute abdominal pain in Turkish pediatric patients: a
      prospective study.
AB  - BACKGROUND: The aim of the present study was to determine the prevalence,
      associated symptoms, and clinical outcomes of children with acute abdominal pain
      who had been admitted to an emergency department. METHODS: Children aged between
      2 and 16 years who presented to the emergency department of Cerrahpasa Medical
      School, Istanbul University between July 2001 and August 2002 with acute
      abdominal pain were enrolled in this study. A questionnaire was completed each
      patient admitted to our pediatric emergency unit for acute abdominal pain. Data
      collected included presenting signs and symptoms, the hospital follow up for all
      children who returned within 10 days, test results, and telephone follow up.
      RESULTS: The number of children referred to the emergency department was 7442,
      with 399 (5.4%) of these having acute abdominal pain. The mean age of the study
      population was 6.9 +/- 3.5 years, and 201 of the patients were male. The five
      most prevalent diagnoses were: (i) upper respiratory tract infection and/or
      complicated with otitis media or sinusitis (23.7%); (ii) abdominal pain with
      uncertain etiology (15.4%); (iii) gastroenteritis (15.4%); (iv) constipation
      (9.4%); and (v) urinary tract infection (8%). The most common associated symptoms
      were decreased appetite, fever and emesis. Because of follow-up deficiency the
      progress of 28 patients was not obtained. Eighty-two children were referred to
      the department of pediatric surgery, but only 17 of 82 (20.7%) required surgical
      intervention (15 of these 17 for appendicitis). Eleven patients returned within
      10 days for re-evaluation, but the initial diagnosis was not changed. The
      complaints of 57 patients with uncertain etiology were resolved within 2 days.
      CONCLUSIONS: An acute complaint of abdominal pain was usually attributed to a
      self-limited disease. However, the percentage of surgical etiology is not
      negligible.

PMID- 15151552
TI  - Semiquantitative scoring in children under treatment for atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is the most frequently seen childhood allergic
      disease in outpatient clinics. Improvement, exacerbation, and response to
      treatment are typically assessed subjectively and occasionally inaccurately.
      METHODS: The authors developed two forms for scoring of dermal manifestations and
      used them to assess 56 children. The correlation between two pediatricians'
      scores and correspondence to established categories (mild, moderate, and severe)
      were determined. RESULT: The two physicians' scores for the children correlated
      well for both forms of scoring. Correspondence of scores as 'mild' and 'moderate'
      categories were significant (few children participating were 'severe').
      CONCLUSION: Use of well-constructed scoring forms should improve clinical
      assessment of patient course and treatment response.

PMID- 15151553
TI  - Staphylococcal enterotoxin-specific IgE antibodies in atopic dermatitis.
AB  - BACKGROUND: The authors clarified the clinical significance of the measurement of
      serum concentrations of specific IgE antibodies to staphylococcal enterotoxin
      (SE) A- and SEB in atopic dermatitis (AD). METHODS: The serum concentrations of
      SEA- and SEB-specific IgE antibodies in 140 pediatric patients with AD were
      measured with an immuno CAP -radioallergosorbent test system (RAST). To check the
      cross-reaction of specific IgE antibodies to SEA/SEB and other allergens, the CAP
      RAST fluorescent enzyme immunoassay inhibition test was performed. RESULTS: Forty
      seven patients (33.6%) tested positive for either SEA- or SEB-specific IgE
      antibodies. School children showed higher positive rates of SEA/SEB-specific IgE
      antibodies than infants or young children. The patients with severe AD and those
      with exacerbation of symptoms in summer, had higher positive rates of SEA/SEB
      specific IgE antibodies than patients with mild AD or those with exacerbation in
      winter. In addition, the positive rates of specific IgE antibodies to both dog
      dander and cat-dander were higher in patients with positive SEA/SEB-specific IgE
      antibodies than in patients with negative ones. No cross-reactions occurred among
      specific IgE antibodies to SEA/SEB and dog/cat dander with one patient's serum,
      which had positive IgE-specific antibodies against cat/dog dander and SEA/SEB.
      The positive rate of SEA/SEB-specific IgE antibodies in the patients with dogs
      and/or cats as pets was 48.4%, which was higher than in those with no pets.
      CONCLUSIONS: Atopic dermatitis patients who exhibit high positive rates of
      SEA/SEB-specific IgE antibodies were found to be school children, severe cases,
      cases with high serum concentrations of total IgE, cases with exacerbation in
      summer, and cases with dogs and/or cats as pets. The measurement of serum
      concentrations of specific IgE antibodies to SEA and SEB, thus has some value for
      evaluating AD patients.

PMID- 15151554
TI  - Utility of scalp-recorded ictal electroencephalograms in childhood epilepsy with
      complex partial seizures.
AB  - BACKGROUND: The authors evaluated the usefulness of scalp-recorded ictal
      electroencephalograms (EEG) in diagnosing the epileptogenic area in epilepsy with
      complex partial seizures. METHODS: The authors analyzed the ictal EEG of 395
      seizures in 43 patients with complex partial seizures. Based on EEG findings the
      patients were classified according to the degree of localization of their onset
      areas. The results were then compared with neuroimaging findings. RESULTS: Only
      10 patients fell into the category 'discrete', meaning that all the onset areas
      (as measured by ictal EEG) were localized in the same lobe of the same
      hemisphere. Seven patients were categorized as 'lateralized', meaning that all
      the onset areas were clearly lateralized in the same hemisphere but without
      consistent localization. Eleven patients were classified as 'localized', meaning
      that the onset area were localized simultaneously in bilateral same lobes, or
      changed consistently from one lobe in one hemisphere to the same lobe in the
      opposite hemisphere. The onset area could not be defined in 15 patients and these
      were categorized as 'not defined'. No patient who underwent seven or more ictal
      recordings was categorized as discrete. However, when confined only to those
      patients in whom over 75% of the ictal recordings showed the same onset area,
      there was a high correlation between the epileptogenic lesions detected by ictal
      EEG and those detected by neuroimaging techniques. CONCLUSIONS: The findings of
      the present study indicate that ictal EEG recordings are useful for determining
      the epileptogenic area in epilepsy with complex partial seizures, provided that
      more than 75% of the ictal recordings show the same ictal onset area.

PMID- 15151555
TI  - Behavioral outcome including attention deficit hyperactivity
      disorder/hyperactivity disorder and minor neurological signs in perinatal high
      risk newborns at 4-6 years of age with relation to risk factors.
AB  - BACKGROUND: Diagnostic problems with the criteria of attention deficit
      hyperactivity disorder (ADHD) in the Diagnostic Statistical Manual, 4th edn, have
      been identified. The aim of this study was to clarify whether the minor
      neurological signs test (MNT) the authors had previously reported was a predictor
      for the criteria of ADHD or hyperactivity disorder (HD) in perinatal risk
      children at 4-6 years of age and what kind of risk factors related to MNT.
      METHODS: A total of 136 children discharged from neonatal intensive care units
      were examined at the age of 4-6 years by a developmental neuropediatrician using
      both MNT and diagnostic criteria of DSM-IV ADHD/ICD-10 (International
      Classification of Diseases, 10th edn) HD. SPSS base and professional were used
      for statistical analysis. RESULTS: On comparison of diagnostic criteria between
      ADHD (11.0%) and HD (27.5%), the incidence in the same subjects showed
      significant difference. MNT scores showed significant correlation with criteria
      of ADHD (P < 0.01) and HD (P < 0.05). Diagnostic validity of MNT for predicting
      ADHD was demonstrated with 78% sensitivity and 79% specificity. High positive
      rates on MNT did not show a significant difference between the very low
      birthweight (VLBW) and non-low birthweight (NLBW) groups. Behavioral outcome with
      relation to risk factors were analyzed using multiple regression analysis. Apgar
      5 in the NLBW group and toxemia of pregnancy and small for gestational age (SGA)
      in VLBW group were highly correlated with behavioral outcome. CONCLUSIONS: Minor
      neurological signs test score was a significant predictor for criteria of ADHD
      and HD. High incidences of positive MNT were suspected in not only VLBW children
      but also NLBW children and Apgar 5 in NLBW children and toxemia of pregnancy and
      SGA in VLBW children influenced behavioral outcome.

PMID- 15151556
TI  - Finlay-Marks syndrome: another sporadic case and additional manifestations.

PMID- 15151557
TI  - Neonate with fetomaternal transfusion differentiated from parvo virus B19
      infection.

PMID- 15151558
TI  - Scrotal hematoma due to neonatal adrenal hemorrhage.

PMID- 15151559
TI  - Neonatal alloimmune thrombocytopenic purpura associated with HPA-5a.

PMID- 15151560
TI  - Macrocephaly-Cutis marmorata telangiectatica congenita with atrial septal
      aneurysm and magnetic resonance imaging (MRI) findings.

PMID- 15151561
TI  - Ceftriaxone-induced biliary pseudolithiasis and urinary bladder sludge.

PMID- 15151562
TI  - Mild immunoglobulin A nephropathy in a patient with a marked increase in serum
      immunoglobulin A.

PMID- 15151564
TI  - Therapy-related membranous nephropathy in juvenile idiopathic arthritis with
      Turner syndrome.

PMID- 15151563
TI  - Child primary tubercular appendicitis.

PMID- 15151565
TI  - Intestinal transport of hypotonic oral rehydration solutions in the rat: regional
      difference of water and electrolyte absorption.

PMID- 15151566
TI  - Red blood cell count and rapid discrimination between thalassemia trait and iron
      deficiency anemia.

PMID- 15151567
TI  - The relationship between nonverbal immediacy, student motivation, and perceived
      cognitive learning among Japanese college students.
AB  - Research in the United States has found a strong and consistent relationship
      between teacher behavior and learning. Data collected from American college
      students indicate that perceptions of teacher nonverbal immediacy (NVI) are
      associated with students' feelings toward learning and perceptions of cognitive
      learning. The purposes of this study were to accomplish the following: (1)
      develop standardized Japanese versions of the instruments used to measure teacher
      nonverbal immediacy, student motivation, and perceived cognitive learning (how
      much students think they have learned); and (2) assess the relationship between
      NVI, student motivation, and perceptions of cognitive learning among Japanese
      college students. Results note that Japanese students report (1) a positive
      relationship between reported levels of teacher NVI and student motivation; (2) a
      negative relationship between reported levels of teacher NVI and perceived
      learning loss; and (3) a negative relationship between student motivation (SM)
      and perceived learning loss (how much students think they did not learn with
      their teacher compared to an ideal teacher). Further, cross-cultural comparisons
      between Japanese and American students were conducted. Results from the cross
      cultural comparison suggest that the relationships between reported teacher
      nonverbal immediacy, student motivation, and learning loss among Japanese college
      students are similar to those found among American college students, but the
      dimensional structure of the questionnaires was different.

PMID- 15151568
TI  - Susceptibility of spatial and verbal working memory to demands of the central
      executive.
AB  - We used a dual-task paradigm to examine the degree to which domain-specific
      spatial and verbal subsystems depend on the domain-general central executive.
      Forty participants were asked to retain spatial or verbal information while
      performing a concurrent secondary task related to simple arithmetic. The
      secondary tasks consisted of three cognitive processes: single-digit addition, a
      digit-carrying operation, and digit reading. The single-digit addition and carry
      operation include central executive functioning, while digit reading relies
      solely on the phonological loop. The single-digit addition caused a performance
      decrement on the spatial working memory task, while the digit reading impaired
      performance on the verbal working memory task. The carry operation interfered
      with recall accuracy on both working memory tasks. The spatial working memory
      task was significantly correlated with the verbal working memory task only when
      the secondary task was more demanding on the central executive. Our results
      suggest that spatial working memory rather than verbal working memory is
      susceptible to failure of central executive functioning and that the central
      executive plays an important role in regulating the cognitive demands of
      different domains.

PMID- 15151569
TI  - Repetition effect in visual recognition of letters.
AB  - This study examined the influence of the repetitive presentation of a letter on
      the recognition of two letters. In two experiments(4), two letters, which were
      either identical or not, were presented successively for a short duration at
      different spatial locations, and the subjects were required to identify them. In
      Experiment 1, the presentation time of the first letter was varied, whereas that
      of the second letter was constant. The results revealed that a reduced
      performance in identifying a second letter was observed in the case that the
      first letter, which was identical to the second letter, could be identified
      correctly. Experiment 2 examined whether or not this reduction was due to the
      identity of the visual shape of two letters. The first letter was presented
      either in the usual vertical orientation or rotated orientation by 180 degrees
      and the second letter was constantly presented in the usual orientation. The
      results revealed that a reduced performance in identifying a repeated letter was
      observed, regardless of the orientation of the first letter. The findings from
      the two experiments suggested that the identity of the information in memory was
      a main cause of the interference effect by repetition.

PMID- 15151570
TI  - Young children's change in strategies of size comparison: Effects of task
      repetition and strategy evaluation.
AB  - This study examined how young children change their strategies for size
      comparison. Twenty-two 5 and 6-year-old children were asked to compare the sizes
      of geometric figures and their strategies were observed once a week over three
      weeks. Half of the children were also asked to evaluate presented strategies for
      comparing geometric figures. It was found that over three weeks not only children
      who evaluated the strategies but also children who did not increased correct
      responses, the strategy of placing one figure on another, and the strategy of
      adjusting two figures by two dimensions. Although more children became aware of
      the effectiveness of those strategies, there was no relationship between the
      evaluation and use of strategies.

PMID- 15151571
TI  - Changes in values cognition after rating values-associated feelings.
AB  - This study investigated values change as an outcome of assessing feelings
      elicited by contemplating the actualization of the same values. The subjects were
      divided into an experimental and a control group. They completed three tests in a
      single session. In the pretest, all subjects were asked to rate the importance of
      20 values items on a 4-point scale. Subjects in the experimental group were then
      asked to rate the degree of pleasure they would feel in actualizing each of the
      values, while those in the control group rated the degree of inequality they
      considered women suffer in the actualization of each of the values. The post-test
      consisted of the same items as the pretest. The subjects in the experimental
      group completed a second post-test 3 months later. It was found that the
      experimental procedure produced significant change in the ratings of 15 values at
      the post-test, whereas the control procedure produced change in only five. The
      results suggest that rating one's emotional response to a value-related situation
      can change one's cognition of that value. At the post-test 3 months later, only 3
      value ratings remained changed.

PMID- 15151572
TI  - Attention-Affect Check List: A self-report measure of acute mental stress.
AB  - Given a hint from Lang, Bradley, and Cutbert's (1997) defense cascade, two
      cognitive processes, instead of passive versus active behavioral coping, which
      seem to have differential effects on the provocation of vascular- versus cardiac
      dominant reaction pattern during mental stress were advocated: attention (Attent)
      versus unpleasant affect (UnplAff). Based on this notion the Attention-Affect
      Check List (AACL) was developed as a self-report measure. In addition, items on
      uncontrollability (Uncontr) were prepared for the purpose of checking whether
      heightened Attent and UnplAff are accompanied by alterations in Uncontr. Two
      hundred and eighty-four students underwent two kinds of mental stress, which
      seemed to specifically heighten Attent and UnplAff. Four factors with four items
      each were extracted from the AACL item pool: concentrated and allocated Attent,
      UnplAff, and pleasant affect. Also, one factor with four items was extracted from
      the Uncontr item pool. For both the mental stresses, each scale, although very
      brief, had quite reasonable alpha reliability. Accountability of each scale for
      the total variance was reasonably high. Some problems are discussed in relation
      to the validity of AACL.

PMID- 15151573
TI  - Effects of self-complexity on mood-incongruent recall.
AB  - Some people cope with negative moods by retrieving positive memories, which is
      mood-incongruent recall. Though mood-incongruent recall is helpful for mood
      regulation, the factors that influence people's ability to utilize mood
      incongruent recall are not well understood. This study investigated whether
      complex knowledge structure is a factor for the ability of mood-incongruent
      recall, based on self-complexity. In the experiment, 50 participants were
      requested to recall positive memories in both neutral and negative moods. The
      results of this study indicated that self-complexity was an important factor
      associated with participants' ability to recall positive memories while they were
      in negative moods. Participants who rated high in self-complexity were those
      whose knowledge is structured in a complex way, recalled more highly positive
      memories in negative moods than in neutral moods. On the other hand, participants
      who were rated low in self-complexity with simple knowledge structures recalled
      memories with a lower extent of positivity in negative moods than those in
      neutral moods.

PMID- 15151574
TI  - Erratum.

PMID- 15151575
TI  - Should Australia introduce a vaccine injury compensation scheme?
AB  - At least a dozen countries or states in the world have introduced vaccine injury
      compensation schemes. This paper argues that the Australian Government should
      introduce such a scheme, which may reduce litigation, and may improve consumer
      and provider confidence. The most important justification, however, is an ethical
      argument from justice and equity: introduction of a vaccine injury compensation
      scheme acknowledges the unique situation that routine childhood immunization is a
      public health measure, given and accepted in good faith, that may occasionally
      damage the recipient.

PMID- 15151576
TI  - The new morbidity in education: the paediatrician's role.

PMID- 15151577
TI  - Bridging the gap between health and education: words are not enough.
AB  - OBJECTIVES: When using specific terminology for childhood developmental
      disorders, paediatricians make assumptions about what teachers know and believe.
      If these assumptions are incorrect, collaborative management may be compromised.
      We surveyed primary school teachers in North Brisbane regarding their beliefs
      about developmental disorders and their views on collaboration between medical
      and educational professionals. METHODS: A survey questionnaire was written
      specifically, and then piloted with professional colleagues and 40 teachers.
      Questions examined teachers' opinions about, and personal experience with various
      developmental disorders. Free comments addressed barriers to collaboration with
      doctors, and how this might be improved. Responses were analysed using
      descriptive statistics. RESULTS: Responses were received from all of the 41
      schools surveyed. Overall, completed questionnaires were obtained from 297 of 397
      (75%) primary classroom teachers surveyed. Several apparent misconceptions were
      held, either by the majority (e.g. 70% felt dietary modification is commonly
      successful treatment for ADHD), or by a significant minority of teachers (e.g.
      23% believed autistic spectrum disorder is not a permanent neurological
      condition). Responses to many questions concurred with the authors' assumptions.
      Teachers reported high levels of concern about lack of training and resource
      support for managing special-needs children. Over three-quarters of teachers did
      not access doctors for information, relying instead on special education
      professionals (96%) or parents (94%). Few group differences were noted by age,
      sex, years teaching experience, or system (Catholic, State). Free comments
      identified significant barriers to the collaboration process, and suggested
      strategies to address these. CONCLUSIONS: Doctors cannot assume teachers' beliefs
      about developmental disorders are similar to their own. Furthermore, doctors
      should recognize constraints that teachers work under, and can take the
      initiative to improve collaboration with topic-based as well as child-specific
      information.

PMID- 15151578
TI  - Aboriginal perspective on middle ear disease in the arid zone of Western
      Australia.
AB  - OBJECTIVES: To explore perceptions, knowledge and experience of otitis media (OM)
      and barriers to compliance with treatment among Aboriginal people of the
      Kalgoorlie-Boulder area, Western Australia. METHODS: This qualitative applied
      research study is based on a holistic design. We conducted structured interviews
      with three community focus groups, 56 key informants, and 22 mothers of babies
      known to have suffered from OM. Written records of interviews were checked with
      participants. The three sources of data enabled comparison and verification of
      results. RESULTS: People were concerned about serious consequences of OM,
      especially deafness and learning difficulties. Since early disease may have no
      localizing symptoms, not surprisingly, people had limited understanding of the
      aetiology of OM and were often only aware of disease once ear discharge was
      visible. Nevertheless, they usually sought treatment for non-specific symptoms.
      Competing demands in people's daily lives and the unpleasant, intensive nature of
      treatment result in families becoming resigned to a child's chronic ear
      discharge. Someone other than the biological mother within the extended family
      may be responsible for administering treatments. Half the carers thought passive
      smoking may predispose children to OM and 70% suggested clearing the nasal
      passages to prevent OM. Results of surgery were viewed positively but specialist
      services were not always readily accessible. CONCLUSIONS: Since responsibility
      for treatment may not lie with the biological mother, awareness campaigns must
      target the entire community. As early OM may be asymptomatic, health personnel
      should be encouraged to do otoscopy on all children with non-specific symptoms.

PMID- 15151579
TI  - Tolerance of interferon-alpha therapy in children with chronic hepatitis B.
AB  - OBJECTIVE: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in
      children with chronic hepatitis B. METHODS: This prospective study was performed
      on one hundred children by interviewing the patients and their parents; clinical
      examinations and laboratory investigations were performed during and after
      therapy. RESULTS: The most frequent side-effects of IFN-alpha therapy were fever,
      flu-like symptoms, and headaches. Lowering of the mean haemoglobin level,
      leukocyte and platelet count was significant, but transient during INF-alpha
      treatment. No increase in autoantibody titres or significant alterations in
      thyroid function was observed. Twelve months after treatment, hepatitis Be
      antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was
      achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg)
      elimination, together with ALT normalization, was achieved in 14% of the cases.
      CONCLUSION: The side-effects of the IFN-alpha therapy in children such as fever,
      flu-like symptoms and bone marrow suppression are common, but transient and mild.

PMID- 15151580
TI  - Skin exposure during conventional phototherapy in preterm infants: A randomized
      controlled trial.
AB  - OBJECTIVE: To assess the effect of reduced skin exposure in preterm infants
      receiving overhead phototherapy treatment on total serum bilirubin (TSB).
      METHODS: Randomized controlled trial. Preterm infants (>1500 g birthweight and <
      or = 36 weeks gestation) were randomized to being nursed either partially clothed
      with only disposable nappies and in posturally supported positions (n = 30) or
      naked without postural support (n = 29). Primary outcome was mean TSB percentage
      change at 24 h of completed conventional overhead phototherapy treatment
      (irradiance of 6 microW cm(-2)/nm at a wavelength of 425-475 nm). The incidence
      of rebound jaundice, number of infants continuing to receive phototherapy
      treatment at 24 h periods, parental stress, mother-infant interaction and mean
      TSB percentage change at 24 h of completed conventional overhead phototherapy
      treatment were examined. RESULTS: Mean TSB percentage change at 24 h of completed
      treatment for the partially clothed group was 15.4% (+/-18) and for the naked
      group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes
      were significantly affected by reduced skin exposure to overhead phototherapy
      treatment. CONCLUSION: Our results show no statistically significant difference
      in TSB level change using either nursing practice.

PMID- 15151581
TI  - Behavioural and physiological reactivity to noise in the newborn.
AB  - OBJECTIVE: To assess the electromyographic (EMG) and behavioural reactivity of a
      group of newborn infants exposed to noisy stimulation of various intensity
      recorded in the Paediatric intensive care Unit (PICU). METHODS: The study was
      performed at the nursery of the Paediatrics Department (University of Padova) on
      a group of 21 healthy newborns (mean 39 weeks of gestation), assessed between 24
      and 72 h after birth. The study involved taking EMG recordings of the corrugator
      supercilii muscle and assessing the infant's behaviour at the baseline (15
      seconds before stimulation), during noisy stimulation (for 1-2 seconds) and
      during recovery (15 seconds in three subphases). The noises, previously recorded
      in PICU, had four different intensities and were administered in random order to
      all infants. Descriptive analysis and repeated-measures analysis of variance
      (anova) were performed on the EMG and behavioural data. RESULTS: The infants
      demonstrated a significant reaction to the noises both in the EMG recordings and
      in behavioural changes, especially during intense noisy stimulation. The reaction
      lasted longer than the stimulation period, preventing the infants from returning
      to the baseline condition. CONCLUSIONS: Exposure to high-intensity noise produced
      in PICU causes evident behavioural and physiological effects (EMG). This is a
      field of study that could have important repercussions, given the medium- and
      long-term effects of repeated noise stimulation.

PMID- 15151583
TI  - Predictors of chronic lung disease in the 'CPAP era'.
AB  - OBJECTIVE: To assess predictors of chronic lung disease (CLD), in infants
      requiring nasal continuous positive airway pressure (CPAP) support in the first 4
      weeks of life. METHODS: A retrospective case note audit of infants of birthweight
      1250 g or less was undertaken. RESULTS: Of 290 infants identified, 50% were
      initially treated with ventilation, 41% with CPAP, 4% required no support, and 5%
      had care withdrawn. Of infants initially treated with CPAP, 23% subsequently
      required ventilation. Overall mortality was 19%, with a further 21% of infants
      developing CLD. For infants requiring CPAP support, requirement for supplementary
      oxygen at between 10 and 21 days predicted increased risk of CLD, and receiver
      operating characteristic curves suggest requirement for supplementary oxygen at
      14 days to be the most reliable cut-off (area under curve = 0.72). Positive
      predictive values for future CLD or death for FiO2 .25, .30 and .40 while on CPAP
      at 14 days were 0.56, 0.61 and 0.76, respectively. CONCLUSIONS: CLD remains
      prevalent in very low birthweight infants in the CPAP era. Oxygen requirement at
      14 days is the strongest predictor of CLD. Infants requiring 30% oxygen or more
      while on CPAP at 14 days have a 60% risk of subsequent CLD or death.

PMID- 15151582
TI  - A randomized trial of two dexamethasone regimens to reduce side-effects in
      infants treated for chronic lung disease of prematurity.
AB  - OBJECTIVE: Dexamethasone has been widely used to reduce the incidence of chronic
      lung disease in preterm infants. However side-effects are common, and the ideal
      dose of dexamethasone has not been identified. We aimed to determine whether an
      individualized course of dexamethasone given to preterm babies at risk of chronic
      lung disease reduced the total dose of dexamethasone administered and reduced
      side-effects compared with a standard 42-day course. METHODS: Thirty-three
      infants in a regional neonatal unit with a birthweight of < or =1250 g who
      required mechanical ventilation at 7 days of age were randomly assigned to a 42
      day course of dexamethasone or an individualized course tailored to their
      respiratory status. The primary outcome was linear growth at 36 weeks corrected
      gestational age. RESULTS: Infants in the individualized course received a 40%
      lower total dose of dexamethasone. However, there was no difference between the
      two groups in linear growth or in the incidence of any other side-effects of
      treatment. There was also no difference in respiratory status or
      neurodevelopmental outcome. CONCLUSION: The individualized course of
      dexamethasone used in this study reduced the total dose of dexamethasone
      administered but did not significantly reduce side-effects of treatment or alter
      outcome in infants at risk of chronic lung disease.

PMID- 15151585
TI  - Obesity and under-nutrition in a tertiary paediatric hospital.
AB  - OBJECTIVE: (i) To determine the prevalence of over- and under-nutrition in both
      inpatients and outpatients in a tertiary paediatric hospital; (ii) to compare the
      prevalence of over-nutrition with that in the Australian community and (iii) to
      determine whether nutritional status has an impact on length of stay in hospital.
      METHODS: Patients aged over 12 months were proportionately sampled from medical
      and surgical wards and outpatient clinics. Data were collected for 245 inpatients
      (54% male) and 272 outpatients (55% male). Children's height, weight and body
      mass index (kg/m2) were measured. Overweight, obesity and under-nutrition were
      defined according to international criteria. Prevalence of overweight and obesity
      was compared with that in the 1995 Australian National Nutrition Survey (NNS).
      RESULTS: Similar proportions of inpatients and outpatients were underweight (6%)
      and wasted (4%). The prevalence of overweight and obesity in inpatients (22%) was
      similar to the NNS but was significantly higher in outpatients (32%, P < 0.0001).
      In a regression model to predict inpatient length of stay, nutritional status (P
      = 0.004) and the interaction between age and nutritional status (P = 0.009) were
      significant predictors. For over-nourished inpatients, length of stay increased
      significantly with age. For normally nourished and under-nourished inpatients,
      length of stay was relatively constant, regardless of age. CONCLUSIONS: There is
      a high prevalence of over-nutrition in paediatric patients, and increased length
      of stay for older over-nourished inpatients. These issues need to be addressed in
      terms of opportunities for intervention and impact on hospital resources.

PMID- 15151584
TI  - Outcomes of a nutrition audit in a tertiary paediatric hospital: implications for
      service improvement.
AB  - OBJECTIVE: To examine the process of anthropometric assessment of nutritional
      status in a tertiary paediatric hospital, to identify the barriers and to make
      recommendations for service improvement. METHODS: The accuracy of height and
      weight scales in wards was checked. Dietitians measured height and weight of a
      representative sample of 245 inpatients and checked whether these measurements
      had been recorded on bed charts. Patients were classified as overweight, obese or
      under-nourished. Diagnoses and procedures were obtained for each patient. Funding
      implications were modelled for inappropriate coding of nutritional status.
      RESULTS: The barriers to nutritional assessment and management of nutritional
      comorbidities were: (i) inaccurate height scales in seven out of 12 wards; (ii)
      under-recording of height and weight on patient bed charts (73% height missing,
      12% both height and weight missing); (iii) under-reporting of obesity and under
      nutrition in medical notes (one of eight obese patients, and none of 28
      undernourished patients, reported); and (iv) low referral rate of obese or under
      nourished children to dietetic services (two of 42 overweight/obese patients
      referred, five of 28 undernourished patients referred). Funding simulation showed
      that if under-nourished patients were correctly diagnosed then the potential
      facility reimbursement would have increased by $A52 326. CONCLUSIONS: Barriers to
      nutritional assessment can lead to failure to diagnose and treat both over- and
      under-nutrition, thereby affecting quality of patient care, and may have
      financial implications for hospitals. Suggestions for service improvement include
      provision of accurate equipment, adequate training of staff undertaking
      nutritional assessments and clear definitions of staff responsibilities in all
      aspects of the process.

PMID- 15151586
TI  - Infant bath seats, drowning and near-drowning.
AB  - OBJECTIVE: To investigate the possible role of infant bathtub seats in drowning
      and near-drowning episodes in infants. METHODS: A review was conducted of the
      files of the Forensic Science Centre and Child Protection Unit, Women's and
      Children's Hospital, Adelaide, South Australia, for significant immersion
      incidents in infants involving bathtub seats from January 1998 to December 2003.
      RESULTS: A total of six cases of drowning occurred over the 6-year period of the
      study in children under 2 years of age, including two infants. One of these
      cases, a 7-month-old boy, had been left unattended for some time in an adult bath
      in a bathtub seat. He was found drowned, having submerged after slipping down and
      becoming trapped in the seat. Three near-drowning episodes occurred in children
      under the age of 2 years, including two boys aged 7 and 8 months, both of whom
      had been left for some time in adult baths in bath seats. Both were successfully
      resuscitated and treated in hospital. CONCLUSIONS: These cases demonstrate the
      vulnerability of infants to immersion incidents when left unattended in bathtubs.
      Bathtubs are particularly dangerous for infants as the slippery and smooth
      surfaces predispose to loss of balance and make escape from water difficult.
      Infant bathtub seats may give parents and child carers a false sense of security
      leading to infants being left unattended. Unfortunately, however, infants may
      fall out of, or slip and become trapped in, such seats. Infants and young
      children cannot be left unsupervised in water, and devices used as bathing aids
      such as bathtub seats may contribute to immersion incidents.

PMID- 15151588
TI  - Severe consequences of sinusitis.

PMID- 15151587
TI  - Nutrition in cerebral palsy.

PMID- 15151589
TI  - Fever in a returned traveller.
AB  - An 8-year-old boy, presenting with fever after returning from a visit to Papua
      New Guinea, was found to have typhoid, despite immunization against this disease
      prior to travel. This most likely represented vaccine failure, although it is
      also possible that he acquired the infection from overseas visitors who had
      stayed with his family prior to his travel, or that he contracted the disease
      from his father. This case highlights the importance of considering typhoid as a
      cause of fever in a returned traveller, even if they have been previously
      immunized against this disease. It also highlights that, in addition to taking
      the patient's travel history, information should be specifically sought about
      contact with visitors from overseas and the travel history of other household
      members.

PMID- 15151590
TI  - Osteomyelitis and pyogenic sacroiliitis: A difficult diagnosis.
AB  - Pyogenic sacroiliitis is an uncommon infection often diagnosed late because of
      poor localization of symptoms and inadequate physical examination. We describe a
      12-year-old girl whose osteomyelitis and pyogenic sacroiliitis was initially
      misdiagnosed and discuss examination, investigation and management of the
      condition. This case highlights the importance of thorough physical examination
      and the consideration of septic arthritis in an unusual joint.

PMID- 15151591
TI  - Delayed disseminated Staphylococcus aureus infection following chickenpox.
AB  - Chickenpox is generally a benign childhood disease. Bacterial superinfection is
      the commonest complication, and can be severe and life-threatening. We describe a
      15-year-old boy with disseminated Staphylococcus aureus infection following
      chickenpox.

PMID- 15151592
TI  - Status dystonicus and Hallervorden-Spatz disease: treatment with intrathecal
      baclofen and pallidotomy.
AB  - Severe dystonia or status dystonicus is a life threatening disorder that develops
      in patients with both primary and secondary dystonia. We present the case of a 9
      year-old boy with Hallervorden-Spatz disease (HVS) who developed status
      dystonicus, failing to respond to high dose oral therapy with multiple
      antidystonic agents. High dose intravenous sedating agents combined with
      endotracheal intubation and mechanical ventilation were required to control the
      spasms. Alleviation of the spasms was achieved by a combination of temporary
      intrathecal baclofen infusions and bilateral pallidotomy. Although it could be
      argued this is a situation where only palliative measures should be used, we
      believe a relatively aggressive approach was justified. It relieved the intense
      pain associated with the spasms and allowed the child to be discharged home
      without the prolonged stay in intensive care, morbidity and mortality, which
      characterize status dystonicus.

PMID- 15151593
TI  - Digoxin dosage error and paediatric cardiology handbook, third edition.

PMID- 15151594
TI  - Respecting the autonomy of participants.

PMID- 15151595
TI  - Privacy, safety and community health.

PMID- 15151596
TI  - Defending de-identification of research samples on the grounds of public health
      benefit.

PMID- 15151597
TI  - Letter of response to editorial by R. Williamson (September 2003).

PMID- 15151599
TI  - Neonatal seizures due to maternal primary hyperparathyroidism.

PMID- 15151600
TI  - Safety of rapid intravenous rehydration.

PMID- 15151602
TI  - Psychosocial adjustment of two boys with gynecomastia.

PMID- 15151603
TI  - The impact of influenza A on children with disabilities.

PMID- 15151604
TI  - Re: Parenteral nutrition solution retrieved by lumbar puncture following left
      saphenous vein catheterization.

PMID- 15151612
TI  - Helicobacter pylori: why are eradication results so variable?

PMID- 15151613
TI  - Traveler's diarrhea.

PMID- 15151614
TI  - Use of imidazole-based eradication regimens for Helicobacter pylori should be
      abandoned in North India regardless of in vitro antibiotic sensitivity.
AB  - BACKGROUND AND AIM: The purpose of this study was to compare the efficacy of
      tinidazole- versus clarithromycin-based triple regimens for eradication of
      Helicobacter pylori in North Indian patients of peptic ulcer disease, and to
      correlate the outcome with in vitro antibiotic susceptibility. METHODS: One
      hundred and forty-six H. pylori-infected patients with active ulcer were included
      in the prospective, randomized study. A total of 70 patients received
      lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d. and tinidazole 500 mg b.d.
      (LAT), and 76 patients received lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d.
      and clarithromycin 500 mg b.d. (LAC) for 14 days. The H. pylori status was
      assessed by urea breath test, rapid urease test, and histology and antibiotic
      sensitivity pattern by Epsilometer test. RESULTS: In per-protocol analysis of 112
      patients the H. pylori eradication rate was 42.3% (95% confidence interval (CI):
      0.29-0.56) in LAT, and 64.8% (95%CI: 0.52-0.78) in LAC (95%CI of difference of
      proportions: 0.13-0.33, P = 0.01). Ulcer healed in 69.2% in the LAT group (95%CI:
      0.57-0.82) and 81.7% in the LAC group (95%CI: 0.72-0.92; P = 0.02). Antibiotic
      susceptibility testing was done in 31 patients. Metronidazole resistance was
      present in 41.9% isolates but was unrelated to the outcome of the LAT regimen.
      CONCLUSION: Imidazole-based eradication regimens should be abandoned in North
      India regardless of in vitro susceptibility results.

PMID- 15151615
TI  - Genetic and phenotype changes following in vitro interactions between
      Helicobacter pylori strains.
AB  - BACKGROUND: The purpose of the present paper was to determine whether in vitro
      interaction between different Helicobacter pylori strains leads to changes in
      antibiotic susceptibility, cagA, vacAM2 and DNA fingerprint patterns. METHODS:
      Three H. pylori strains with known antibiotic susceptibility, cagA, vacAM2 status
      and polymerase chain reaction-random amplified polymorphic DNA (PCR-RAPD)
      fingerprint analysis were suspended in phosphate buffered saline (PBS pH 7.0),
      and the suspensions were mixed in equal proportion prior to culture on chocolate
      agar plates. Subcultures were performed five times every 3 days. As a control,
      each of the three strains was also subcultured separately. Antibiotic
      susceptibility testing, PCR for cagA, vacAM2 and PCR-RAPD analysis were done.
      RESULTS: Surviving strain of the two H. pylori strains in each combination
      demonstrated change in resistance to both antibiotics but no change in
      sensitivity. CagA status of the surviving strain varied as compared to the vacAM2
      status, which did not change. The PCR-RAPD fingerprint showed unique band
      pattern. CONCLUSION: DNA transformation follows in vitro interaction.
      Helicobacter pylori strain with antibiotic resistance is likely to dominate in
      such in vitro interactions between various strains.

PMID- 15151616
TI  - Association between diet and esophageal cancer in Taiwan.
AB  - BACKGROUND: Several studies have reported the importance of dietary factors in
      the development of esophageal cancer. The purpose of the present study was to
      evaluate the effects of several common dietary factors on the risk of squamous
      cell carcinoma of the esophagus in a Taiwanese population. METHODS: The
      association between diet and esophageal cancer was examined in 284 male patients
      and 480 male controls, who were recruited during 6 year period. RESULTS:
      Consumption of preserved and overheated foods was found to be associated with
      increased risk of esophageal cancer, whereas intake of fresh fruits, vegetables,
      and tea was inversely associated with this risk. Men who consumed fermented bean
      products, salted food and preserved/pickled vegetables more than once a week
      after age 40 years had a 3.4-fold risk (95% confidence interval (CI): 1.9-6.2),
      2.3-fold risk (95%CI: 1.2-4.2), and 2.5-fold risk (95%CI: 1.3-4.5), respectively,
      compared to men eating these items less than once a week. It was further found
      that these preserved foods were more strongly associated with esophageal cancer
      among men who consumed fruit less than once per day than those who consumed
      fruits one or more times per day. CONCLUSIONS: These results suggest that a high
      intake of preserved foods and overheated drinks might increase the risk of
      esophageal cancer, and intake of fruit, vegetables, and tea might be negatively
      associated with risk of esophageal cancer. The results also suggest that diet is
      an important factor in the development of esophageal cancer in Taiwan.

PMID- 15151617
TI  - Expression of cyclooxygenase-2 (COX-2) in human esophageal cancer and in vitro
      inhibition by a specific COX-2 inhibitor, NS-398.
AB  - BACKGROUND: The purpose of the present paper was to study the expression of
      cyclooxygenase-2 (COX-2) in normal squamous epithelium, squamous dysplasia and
      squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX-2 in
      esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a
      COX-2 inhibitor, NS-398, in inducing growth inhibition and apoptosis of human
      esophageal cancer cells. METHODS: Biopsy specimens of esophageal dysplasia (n =
      21), and surgical resections of SCC (n = 37) were compared with normal esophagus
      (n = 37) and analyzed by RT-PCR. Human esophageal cells were used for the study.
      Anti-proliferative effect was measured by MTT, apoptosis was determined by DNA
      fragmentation assay. RESULTS: Marked COX-2 expression was shown in SCC and
      esophageal squamous dysplasia, and no marked COX-2 expression was observed in the
      normal squamous epithelium, respectively. NS-398 could inhibit esophageal cells
      growth in a dose-dependent manner, induce apoptosis, and elevate caspase-3
      activity in vitro. CONCLUSIONS: This study provides evidence that COX-2 is
      upregulated in the majority of cases of squamous dysplasia and SCC of esophagus,
      and that NS-398 can inhibit growth and induce apoptosis via activating caspase-3
      activity in vitro. These results suggest that selective inhibitors of COX-2 may
      be an effective preventive and therapeutic option for esophageal carcinoma.

PMID- 15151618
TI  - Complement regulatory proteins in normal human esophagus and esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Altered expression of three complement regulatory proteins, decay
      accelerating factor (CD55), membrane cofactor protein (CD46) and homologous
      restriction factor 20 (CD59) has been identified in human gastrointestinal
      malignancies, but their expression in esophageal cancer has not been described.
      Therefore the purpose of the present paper was to study the distribution of these
      proteins in human normal and malignant esophageal mucosa. METHODS AND RESULTS: In
      the normal esophageal mucosa, CD55 predominantly stained on the cell membrane of
      squamous epithelium in the superficial and prickle cell layers, whereas CD46 most
      intensely stained on the cell membrane in the basal and parabasal cell layers. In
      contrast to this reciprocal expression of CD55 and CD46, CD59 was broadly
      distributed on the cell membrane in all layers. In the esophageal squamous cell
      carcinoma, CD55 staining was intense in the stroma but was negligible in the
      cancer cells. In contrast, CD46 and CD59 stained almost uniformly on the tumor
      cell membrane. There was a significant difference in the intensity of the
      staining of CD55 and CD46 among cells in various layers of normal esophageal
      mucosa and esophageal carcinoma cells, but not in the staining of CD59. Similar
      expression patterns of the three complement regulatory proteins in carcinoma
      cells and in normal epithelium in the basal and parabasal cell layers were
      observed. CONCLUSIONS: These observations on the expression of the three
      complement regulatory proteins would help understanding of the host immune
      responses involving the complement system against esophageal squamous cell
      carcinoma.

PMID- 15151620
TI  - Gastric emptying function changes in patients with thyroid cancer after
      withdrawal of thyroid hormone therapy.
AB  - BACKGROUND: Hypothyroidism is commonly thought to cause decreased gastric
      emptying but is mostly associated with autoimmune disease. In the present study
      the gastric emptying function of thyroid cancer patients with severe
      hypothyroidism of short duration was evaluated with a radionuclide solid meal
      gastric emptying study. METHODS: Twenty-two patients who had undergone surgical
      operation and (131)I ablation for thyroid cancer participated in solid meal
      gastric emptying studies before the withdrawal of thyroxine and then again 4
      weeks after the withdrawal of thyroxine. Eleven patients had an additional
      gastric emptying study at 6 weeks after withdrawal of thyroxine. Gastric emptying
      curves and emptying parameters were calculated. Student's paired t-test was used
      for statistical analysis of data for all cases between the baseline and at 4
      weeks after withdrawal. An additional repeated measure anova with multiple
      comparisons was performed on data between baseline, 4 weeks and 6 weeks after
      withdrawal for the other 11 patients. All P values presented are two-tailed and
      the significance level is 0.05. RESULTS: Hypothyroidism status was confirmed by
      the marked change of the serum thyroxine and thyroid-stimulating hormone 4 weeks
      and 6 weeks after withdrawal of the thyroxine replacement (P < 0.001). The
      gastric half-emptying time and emptying rate changed significantly after short
      term severe thyroid hormone deficiency (P < 0.005). However, the length of the
      lag phase did not have a statistically significant change at 4 weeks or 6 weeks
      after withdrawal of the thyroxin replacement (P = 0.219 and 0.142). CONCLUSIONS:
      Hypothyroidism following the withdrawal of the thyroxine replacement in thyroid
      cancer patients preparing for (131)I cancer work-up can significantly prolong
      gastric half-emptying time and emptying rate.

PMID- 15151619
TI  - Clinicopathological significance of vascular endothelial growth factor-C and
      cyclooxygenase-2 in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is a specific growth
      factor of lymphatics, which is known to play some role in tumor growth and
      metastasis to lymph nodes and distant organs in various malignancies. The purpose
      of the present study was to investigate the expression of VEGF-C in human
      esophageal squamous cell carcinomas (ESCC) to elucidate its role in tumor
      progression and lymph node metastasis. Another aim of the study was to
      investigate the relation between VEGF-C and cyclooxygenase-2 (COX-2) in ESCC.
      METHODS: The expression of VEGF-C and COX-2 in ESCC was evaluated in 13
      endoscopic mucosal resection specimens and in 21 surgical specimens by
      immunohistochemical staining. Clinical data were obtained from medical records.
      RESULTS: The degree of VEGF-C expression increased as the depth of primary tumor
      progressed (r = 0.521, P = 0.002), the stage progressed (r = 0.572, P < 0.001),
      and the degree of COX-2 expression increased (r = 0.387, P = 0.024). The VEGF-C
      positive rate was different between early cancers in which regional lymph node
      metastasis was thought to be absent and advanced cancers in which regional lymph
      node metastases were confirmed after surgery (20.0% vs 100.0%; P < 0.001).
      CONCLUSIONS: The VEGF-C expression in ESCC is related to COX-2 expression, and
      VEGF-C is also associated with the depth of primary tumor, the stage, and
      probably lymph node metastasis. Thus the investigation of VEGF-C expression in
      ESCC may assist in management planning.

PMID- 15151621
TI  - Gastric electrical activity in patients with cholelithiasis undergoing
      laparoscopic cholecystectomy: a prospective controlled study.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of gallstone
      disease (GD) and laparoscopic cholecystectomy on gastric electrical activity of
      slow waves, which was recorded via transcutaneous electrogastrography (EGG).
      METHODS: Twenty-one consecutive patients (M/F: 12/9, 52.7 +/- 15 years old) with
      GD and no previous history of abdominal operations or known disease affecting
      gastrointestinal motility were studied. The EGG was performed for 30 min prior to
      and 90 min after a standard meal, during a 4-6 month period prior to and after
      laparoscopic cholecystectomy. The percentile proportion of the three spectra of
      gastric slow waves frequency was studied, defined as follows: bradygastria, 1-2.1
      cycles per min (c.p.m.); normogastria, 2.2-3.9 c.p.m.; and tachygastria, 4-9
      c.p.m. The findings were compared to those of nine healthy subjects (M/F: 5/4,
      49.5 +/- 14.8 years old). RESULTS: No statistically significant difference was
      found in percentile distribution of bradygastria, normogastria and tachygastria,
      pre- or post-prandially, neither before or after laparoscopic cholecystectomy,
      nor between patients and controls. CONCLUSIONS: Patients with GD do not exhibit
      differences in gastric electrical activity of slow waves in comparison to normal
      subjects and laparoscopic cholecystectomy does not alter gastric electrical
      activity. These findings suggest that cholelithiasis does not seem to cause
      dyspeptic symptoms due to gastric dysrythmias.

PMID- 15151622
TI  - Hepatocellular carcinoma in Saudi Arabia: role of hepatitis B and C infection.
AB  - BACKGROUND AND AIM: To estimate the risk of hepatocellular carcinoma (HCC) in non
      alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi
      Arabia were compared with 118 age- and sex-matched healthy individuals. RESULTS:
      The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7
      75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0-12.9) in the
      controls (OR: 28.4; 95%CI: 12.6-63.9; P < 0.001). There was a high risk of HCC in
      the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8-79.1, P < 0.001) and anti-HCV
      alone (OR: 12.2; 95%CI: 3.2-47.2; P < 0.001). Although HBV and HCV were
      independent risk factors in the development of HCC, there was no interactive
      relationship between the two viruses. Dual infections occurred in only 3.4% and
      were associated with only a moderate increase in the risk of HCC (OR: 14.6;
      95%CI: 1.57-135.9). In 24.6% of the cases no virus was identified as the
      etiologic factor. CONCLUSION: Hepatitis B virus constitutes a major risk factor
      and HCV contributes a less significant role in the development of HCC. The
      ongoing program of HBV vaccination may significantly decrease the prevalence of
      HBV-associated HCC in this population.

PMID- 15151623
TI  - High viral load is a risk factor for hepatocellular carcinoma in patients with
      chronic hepatitis B virus infection.
AB  - BACKGROUND AND AIMS: Hepatitis B virus (HBV) is considered a major risk factor
      for the progression to liver cirrhosis and hepatocellular carcinoma (HCC). The
      serum level of HBV-DNA is correlated with progression of the disease. The aim of
      the present study was to determine the relationship between the level of HBV-DNA
      and hepatocarcinogenesis in patients with chronic HBV infection. METHODS: The
      authors studied 73 patients who were diagnosed with chronic HBV infection at
      Nagasaki University Hospital (Nagasaki, Japan) between January 1980 and December
      1999. The significance of age, sex, habitual drinking, serum alanine
      aminotransferase level, HBV viral load, interferon treatment, hepatic fibrosis
      and hepatic inflammation on the development of HCC were examined using univariate
      and multivariate analyses. RESULTS: The cumulative incidence rates of HCC were
      14%, 29% and 48% at 5, 10 and 15 years after liver biopsy, respectively.
      Multivariate analysis identified high viral load, together with age and severe
      fibrosis, as independent and significant risk factors (P = 0.045, 0.047 and
      0.013, respectively) for HCC. CONCLUSIONS: The present findings indicate that
      high viral load is a risk factor for HCC in patients with chronic HBV infection.
      Patients with a high HBV viral load should be carefully monitored for HCC.

PMID- 15151624
TI  - Cadherin/catenin complex appears to be intact in hepatocellular carcinomas from
      Australia and South Africa.
AB  - BACKGROUND AND AIM: E-cadherin binds to beta-catenin to form the cadherin/catenin
      complex required for strong cell adhesion. Inactivation of this complex in tumors
      facilitates invasion into surrounding tissues. Alterations of both proteins have
      been reported in hepatocellular carcinomas (HCC). However, the interactions
      between E-cadherin and beta-catenin in HCC from different geographical groups
      have not been explored. The aim of the present study was to assess the role of E
      cadherin and beta-catenin in Australian and South African patients with HCC.
      METHODS: DNA was extracted from malignant and non-malignant liver tissue from 37
      Australian and 24 South African patients, and from histologically normal liver
      from 20 transplant donors. Chromosomal instability at 16q22, promoter methylation
      at E-cadherin, beta-catenin mutations and E-cadherin and beta-catenin protein
      expression was assessed using loss of heterozygosity, methylation-specific
      polymerase chain reaction, denaturing high-performance liquid chromatography and
      immunohistochemistry, respectively. RESULTS: Loss of heterozygosity at 16q22 was
      prevalent in South African HCC patients (50%vs 11%; P < 0.05, chi(2)). In
      contrast, E-cadherin promoter hypermethylation was common in Australian cases in
      both malignant (30%vs 13%; P = not significant, chi(2)) and non-malignant liver
      (57%vs 8%, respectively, P < 0.001, chi(2)). Methylation of non-malignant liver
      was more likely to be detected in patients over the age of 50 years (P < 0.001,
      chi(2)), the overall mean age for our cohort of patients. Only one beta-catenin
      mutation was identified. E-cadherin protein expression was reduced in one HCC,
      while abnormalities in protein expression were absent in beta-catenin.
      CONCLUSION: Contrary to previous observations in HCC from other countries,
      neither E-cadherin nor beta-catenin appears to play a role in
      hepatocarcinogenesis in Australian and South African patients with HCC.

PMID- 15151625
TI  - Combined supplementation of vanadium and beta-carotene suppresses placental
      glutathione S-transferase-positive foci and enhances antioxidant functions during
      the inhibition of diethylnitrosamine-induced rat liver carcinogenesis.
AB  - BACKGROUND AND AIM: The present study was designed to investigate the
      chemopreventive effects of combined vanadium (V; 0.5 p.p.m.) and beta-carotene
      (BC; 120 mg/kg of basal diet) on diethylnitrosoamine (DEN)-induced and
      phenobarbital (PB)-promoted rat hepatocarcinogenesis. METHODS: All rats were
      subjected to two-thirds partial hepatectomy (PH) at the fourth week. After PH
      they were administered either trioctanoin alone (groups A', B', C' and D') or a
      single injection of DEN in trioctanoin at a dose of 10 mg/kg of body weight
      (groups A, B, C and D). Two weeks after the DEN treatment PB was administered
      (0.05% in basal diet) to all the DEN-treated rats and continued until the end of
      the experiment. Supplementation of V (groups B and B'), BC (groups C and C') or
      both V and BC (groups D and D') at the doses stated previously were started 4
      weeks before DEN administration (at week 0) and continued until the 16th week.
      RESULTS: It was observed that in the DEN-treated and PB-promoted group (group A)
      the expression of the numbers and areas of the placental form of glutathione S
      transferase (GST-P)-positive altered hepatic foci (AHF) was maximum. Treatment
      with V (group B) and BC (group C) significantly reduced the expression of GST-P
      positive AHF by 29.5% and 42.8%, respectively. An additive protection action
      (65.7%) was noticed in group D, which received both V and BC for the entire
      period of the experiment. It was also observed that supplementation of V and BC
      for the entire period of the experiment significantly reduced the number and size
      of the hyperplastic nodules, while the combination treatment worked as an
      additive effect, reducing the number and size of the hyperplastic nodules to 22%
      from 89%. Moreover, a significantly reduced level of cytosolic glutathione (P <
      0.001) and glutathione-S-transferase (P < 0.001) activity and stabilization of
      aerobic metabolism and hepatic architecture of the cells as compared with
      carcinogen control were observed in the V + BC-treated group. CONCLUSION: The
      present study suggests that V, an essential trace element, may be useful in
      combination with BC, an antioxidant, in the inhibition of experimentally induced
      rat hepatocarcinogenesis.

PMID- 15151627
TI  - Clinical and pathological characteristics of the autoimmune hepatitis and primary
      biliary cirrhosis overlap syndrome.
AB  - BACKGROUND AND AIMS: The defining of the autoimmune hepatitis (AIH) and primary
      biliary cirrhosis (PBC) overlap syndrome as a separate clinicopathological entity
      has been controversial and temporally and geographically subjective. METHODS:
      From 1979 until 2000, 227 patients diagnosed with AIH, PBC or the overlap thereof
      were treated. Cases with genuine AIH/PBC overlap syndrome were sorted out using
      close clinical follow up and serial liver biopsies. RESULTS: Of the 227 patients,
      19 (8.4%) were diagnosed with the AIH/PBC overlap syndrome. They all cleared a
      score >10 for the diagnosis of AIH, and tested positive for antimitochondrial
      antibodies during their courses. Long-term follow up with frequent histological
      examinations, however, established the diagnosis of AIH/PBC overlap syndrome in
      only two (0.8%) patients. The most powerful factor distinguishing AIH from PBC
      was acidophilic bodies in lobules that were detected significantly more
      frequently in patients with AIH than PBC or spurious overlap syndrome (39/46
      [85%]vs 3/85 [4%], P < 0.001). It was more reliable than bile-duct lesions for
      the distinction of PBC from AIH. CONCLUSIONS: Although AIH/PBC overlap syndrome
      does exist, it is infrequent and needs to be diagnosed carefully using close
      clinical and histological follow up to enable timely and effective treatment.

PMID- 15151626
TI  - Insulin resistance and C-reactive protein as independent risk factors for non
      alcoholic fatty liver disease in non-obese Asian men.
AB  - BACKGROUND AND AIM: Although insulin resistance is often considered the link
      between obesity and non-alcoholic fatty liver disease (NAFLD), the role of
      insulin resistance, independent of obesity, as a NAFLD risk factor in non-obese
      men has been less well established. Systemic inflammation may be accompanied by
      insulin resistance in healthy subjects. The goal of the present study was to
      examine if insulin resistance and systemic inflammatory markers are independent
      predictors of NAFLD in non-obese men. METHODS: The authors conducted a cross
      sectional survey of 120 patients with NAFLD and 240 controls matched by age and
      body mass index. Controls had no evidence of alcohol abuse, hepatitis B or C,
      obesity, or previous history of diabetes, fasting hyperglycemia or hypertension.
      Diagnosis of NAFLD was based on an elevated alanine aminotransferase level and
      sonographic evidence of a fatty liver. Insulin resistance was determined using a
      homeostasis model assessment (HOMA-IR). RESULTS: The age-adjusted risk of
      developing NAFLD was strongly associated with the elevated levels in measurements
      of uric acid, fasting blood sugar, triglycerides, apolipoprotein B, C-reactive
      protein (CRP) and HOMA-IR, and decreased levels of high density lipoprotein
      cholesterol and apolipoprotein A-I. Multivariate analysis based on univariate
      analysis indicated that an increase in CRP (odds ratio [OR] = 1.37; 95%
      confidence interval [CI]: 1.06-1.77) per 1 SD (1.48 mg/L) and HOMA-IR (OR = 2.28;
      95% CI: 1.67-3.11) per 1 SD (0.63) were independent risk factors for NAFLD.
      CONCLUSION: Insulin resistance and systemic inflammatory response are of key
      importance for inducing NAFLD, particularly in apparently healthy non-obese men.

PMID- 15151628
TI  - Images of Interest. Gastrointestinal: aphthous lesions to overt Crohn's disease.

PMID- 15151629
TI  - Images of Interest. Gastrointestinal: squamous papilloma of the esophagus.

PMID- 15151630
TI  - Images of interest. Hepatobiliary and pancreatic: intrahepatic hemorrhage from
      hepatic adenoma.

PMID- 15151631
TI  - Images of Interest. Hepatobiliary and pancreatic: gastrointestinal bleeding and
      pancreatic pseudocysts.

PMID- 15151632
TI  - HFE gene and hemochromatosis.

PMID- 15151633
TI  - Painful jaundice revealing Kawasaki disease in a young man.
AB  - Liver involvement is usually a minor manifestation of Kawasaki disease and
      includes hepatobiliary dysfunction or gallbladder hydrops. We describe here an
      unusual case of jaundice revealing an adult onset Kawasaki disease. An 18-year
      old man presented with abdominal pain and jaundice associated with cholestasis as
      the initial manifestation of Kawasaki disease. Abdominal evaluation
      (ultrasonography and CT-scan) did not find abnormality. Other signs typical of
      the Kawasaki disease occurred a few days later and permitted diagnosis. With
      aspirin and intravenous immunoglobulins, outcome was favorable without any
      cardiovascular complication. Our case suggests that Kawasaki disease should be
      added to the etiological list of painful febrile icterus in young patients.

PMID- 15151635
TI  - Hepatitis C infection with history of tuberculosis in Japan: no association with
      progression of liver fibrosis.

PMID- 15151634
TI  - Complete remission of metastatic pancreatic cancer with cardiac involvement after
      gemcitabine, oxaliplatin and 46-h infusion of 5-fluorouracil/leucovorin.

PMID- 15151636
TI  - Regression of a hepatocellular carcinoma following treatment with octreotide and
      tamoxifen in a patient with advanced alcoholic cirrhosis.

PMID- 15151637
TI  - Superior mesenteric artery (Wilkie) syndrome: different faces.

PMID- 15151638
TI  - Angiomyolipoma of the liver causing Budd-Chiari syndrome.

PMID- 15151640
TI  - Hemobilia caused by pseudoaneurysm of the cystic artery.

PMID- 15151639
TI  - Reversible decompensated liver disease as a possible complication of pegylated
      interferon alfa 2b and ribavirin for recurrent hepatitis C.

PMID- 15151641
TI  - Bilateral choroidal metastasis as the initial manifestation of a rectal cancer.

PMID- 15151643
TI  - Percutaneous catheter ablation procedures for the treatment of atrial
      fibrillation.
AB  - In light of the significant morbidity and mortality from atrial fibrillation
      (AF), there has been significant interest in the development of percutaneous
      catheter ablation procedures for the suppression of AF. Given the success of the
      surgical Maze procedure, initial catheter-based approaches involved creation of
      linear atrial lesions. Success rates were low and utility was limited by a high
      complication rate and long procedural times. The recent discovery that AF is
      often initiated by atrial ectopic beats has resulted in therapies designed to
      target the ectopic sources, particularly those within the pulmonary veins.
      Experience and technological advances have improved the efficacy and safety of
      such procedures. This article will review catheter ablation procedures for the
      maintenance of sinus rhythm in patients with AF.

PMID- 15151644
TI  - Alternative energy sources for surgical atrial ablation.
AB  - As less complex modifications of the Maze procedure have been developed, a number
      of energy sources have been introduced to facilitate the creation of electrically
      isolating lesions within the atria. These include cryoablation, radiofrequency,
      microwave, laser, and focused ultrasound. Although each of these sources works
      slightly differently, the goal of all thermal sources is to heat tissue to a
      temperature (50 degrees C) above which irreversible electrical isolation occurs.
      These sources have been utilized both endocardially in arrested heart procedures
      as well as epicardially in the beating heart setting. There are several obstacles
      to the use of these sources epicardially, mostly related to the heat sink effect
      of endocardial blood. Several recent modifications have been introduced that will
      hopefully increase the efficacy of these sources in beating heart applications.

PMID- 15151645
TI  - Atrial ablation for the surgical treatment of atrial fibrillation: principles and
      limitations.
AB  - This article reviews the development of procedures designed to eradicate atrial
      fibrillation by creating nonincisional lesions in the atria. Percutaneous
      interventional and surgical data are reviewed and analyzed. A major limitation of
      the surgical approaches, which utilize a variety of energy sources, appears to be
      the difficulty in achieving transmurality in all patients. A second limitation is
      related to a poor understanding of the underlying mechanisms of atrial
      fibrillation, and the consequent uncertainty as to the ideal lesion
      configurations necessary to counter these mechanisms. The article also discusses
      the various types of clinical atrial fibrillation, and discusses the differences
      between endocardial and epicardial application of thermal energy sources.
      Finally, atrial contractility is addressed, and the authors conclude that the
      ideal procedure will achieve a balance between conversion to normal sinus rhythm
      and the preservation of atrial contractility.

PMID- 15151646
TI  - Pulmonary vein isolation by microwave energy ablation in patients with permanent
      atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is associated with significant morbidity and
      mortality. Microwave energy ablation (MW) is a new option for surgical treatment
      of permanent atrial fibrillation (pAF). We present our experience with surgical
      treatment of mitral valve disease (MVD), coronary artery disease (CAD), and
      aortic valve disease (AVD) and microwave ablation in patients with pAF. METHODS:
      In 202 consecutive patients (100 female, 102 male, age 68.3 +/- 8.1 years from
      30.4 to 83.5 years, ejection fraction 25-80%, left atrial diameter 56 +/- 9.1 mm
      from 30 to 102 mm) with an indication for a cardiosurgical intervention, pAF was
      documented for 6.8 +/- 9.1 years. MW was performed using two different lesion
      concepts. In the first 140 patients we used an ablation line starting at the
      posterior mitral valve annulus and incorporated the interior of all pulmonary
      veins. After the first 137 patients we switched to a different ablation line
      concept. Starting at the posterior mitral valve the annulus ablation line
      additionally included the left atrial appendix. Another ablation circle around
      the pulmonary veins of both sides was created and both circles were connected. If
      opening of the right atrium was necessary additional isthmus ablation was
      performed. RESULTS: Survival rate was 98.5%. There were no ablation-related
      complications. In the 6-month follow-up 87 patients were in sinus rhythm (65%),
      in the 1-year follow-up 74 patients were in SR (62.2%). CONCLUSIONS: Microwave
      ablation is a safe and efficient method for surgical treatment of pAF in patients
      with a concomitant cardiosurgical procedure. The short duration for this
      additional procedure and easy application has made this procedure the method of
      choice in our institution for treatment of pAF in patients with cardiosurgical
      operations.

PMID- 15151647
TI  - Minimally invasive surgery for atrial fibrillation: toward a totally endoscopic,
      beating heart approach.
AB  - In the last several years, a number of procedures have been conceived that have
      attempted to treat atrial fibrillation (AF) by creating a limited set of lesions
      modeled after those of the Maze operation. These lesions have been created by a
      variety of means, including the traditional cut-and-sew method, but also by
      nonincisional techniques. These have included cryoablation as well as several
      thermal techniques, using radiofrequency, microwave, laser, and focused
      ultrasound energy. One reason for the development of these nonincisional
      techniques has been the desire to develop less invasive operations for the
      treatment of AF. The specific goal of our center has been to utilize these energy
      sources as well as other minimally invasive tools, such as surgical robots, to
      develop a closed chest, off-pump procedure for AF. The development of such a
      procedure is outlined in this article.

PMID- 15151648
TI  - N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total
      circulatory arrest.
AB  - OBJECTIVE: We hypothesized that the use of N-acetylcysteine would ameliorate the
      lung reperfusion injury observed after deep hypothermia and total circulatory
      arrest (DHTSA). METHODS: Experiments were carried out on 12 adult mongrel dogs of
      either sex weighing 25 to 30 kg. The animals were randomly divided into two
      groups of six animals each. All animals were cooled to an esophageal temperature
      of 15 degrees C during 30 minutes and underwent 60 minutes of DHTSA, followed by
      the reinstitution of cardiopulmonary bypass (CPB) and rewarming. Before
      rewarming, while 100 mL physiologic saline solution was added into the pump in
      group I, 50 mg/kg N-acetylcysteine(NAC) was given in group II. Heart rate, mean
      arterial pressure, pulmonary arterial pressure, left atrial pressure, central
      venous pressure, and cardiac output were recorded. To measure lung tissue
      malondialdehyde (MDA), water content and polymorphonuclear leukocytes (PMNs)
      count, lung tissue samples were taken before CPB and after weaning CPB. In
      addition, alveolar-arterial oxygen difference (AaDO(2))()for tissue oxygenation
      was calculated by obtaining arterial blood gas samples. Dynamic lung compliance
      (DLC) was measured before CPB and after CPB. RESULTS: MDA levels before CPB of
      44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g tissue after weaning CPB
      in group I (p = 0.004). In group II also, the MDA levels increased from 43.5 +/-
      4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after weaning CPB (p = 0.006). The MDA
      increase in group II after CPB was found to be significantly lower than in group
      I (p = 0.006). The wet-to-dry lung weight ratio in the NAC group was 5.1 +/- 0.2,
      significantly less than in the control group (5.9 +/- 0.3), (p = 0.004). AaDO(2)
      significantly increased in the group I and II (p = 0.002 and p = 0.002,
      respectively); this elevation in group I was significant than in group II (p =
      0.044). In histopathological examination, it was observed that neutrophil counts
      in the lung parenchyma rose significantly after CPB in both groups (p < 0.001).
      The increase in group I was significantly larger than group II (p < 0.001).
      CONCLUSIONS: Results represented in our study indicate that addition of NAC into
      the pump after DHTSA can reduce lung reperfusion injury.

PMID- 15151650
TI  - The role of corticosteroid therapy following surgery for atrial fibrillation.
AB  - BACKGROUND: The objective of our study was to evaluate the usefulness of steroids
      therapy for patients who underwent surgery for chronic atrial fibrillation, with
      histologic findings of myocarditis. METHODS: Between April 1991 and July 2002,
      144 patients underwent surgery for chronic atrial fibrillation at the time of
      other cardiac operations, at the Department of Cardiovascular surgery of the
      University of Bologna. Fragments of left and right appendages were provided for
      each patient for histologic study: In three patients myocarditis was identified
      and they were treated with steroid therapy until the postoperative day 60. We
      report here the case of our first successfully treated patient with a longer
      follow-up time. RESULTS: The patient was discharged on postoperative day 30, in
      sinus rhythm. At follow-up, 9 months after surgery, she was doing well and
      working full time; the ECG showed sinus rhythm, and echocardiography demonstrated
      biatrial contraction. CONCLUSIONS: According to our experience, the histologic
      diagnosis of myocarditis allowed us to modify the therapeutic approach in
      patients who underwent surgery for atrial fibrillation, in which the addition of
      steroids to antiarrhythmic therapy, in the early postoperative period, is able to
      induce the recovery of sinus rhythm.

PMID- 15151649
TI  - The Edwards MIRA heart valve prosthesis: a 2-year study.
AB  - BACKGROUND: The Edwards MIRA mechanical heart valve is designed to optimize
      hemodynamics, reduce thrombogenicity, and avoid mechanical failure with a special
      hinge mechanism. The purpose of the study was to investigate the clinical
      performance and postoperative hemodynamic results of the first European patients
      receiving Edwards MIRA mechanical heart valves. METHODS: From March 1998 to March
      1999 a total of 54 Edwards MIRA valves model numbers 3600 (aortic, n = 44) and
      9600 (mitral, n = 10) were implanted in 52 (36 male, 16 female; mean age 61 +/-
      10.1 years) consecutive patients undergoing mechanical valve replacement in a
      prospective study. Follow-up of the patients including physical examination, ECG,
      blood tests, and Doppler were performed prior to discharge, at 6 months, at 1
      year, and at least 2 years postoperatively. RESULTS: Through October 2001 a total
      of 172 follow-up examinations were completed (51 patients at discharge, 46
      patients at 6 months, 43 patients at 12 months, 32 patients at 2 years or
      beyond). All patients were in NYHA class I and II at the 6-month and 2+-year
      follow-up. All the patients stated an improved quality of life. Hospital
      mortality was 1.9%. There were no complications related to anticoagulation. Mean
      international normalized ratio at 6 months was 3.2 (range 1.9 to 4.3); lactate
      dehydrogenase was slightly increased with 264 +/- 103 U/L on average (normal
      value 80 to 240 U/L). No signs of valvular dysfunction or paravalvular leakage
      were observed. Mean pressure gradients were related to valve diameter: after
      mitral valve replacement (size 27, 29, 31 mm: 4.8, 3.2, 2.1 mmHg); after aortic
      valve replacement (size 19, 21, 23, 25 mm: 12.1, 13.1, 9.3, 8.2 mmHg).
      CONCLUSIONS: These preliminary data suggest good hemodynamic function and a low
      rate of valve-related complications of the Edwards-MIRA mechanical prosthesis.

PMID- 15151651
TI  - Contemporary results of total aortic arch replacement.
AB  - BACKGROUND AND AIM: Aneurysmal dilatation of the aortic arch is uncommon, and the
      complex anatomy involved imposes unique technical challenges. The results of
      surgical intervention reported from large centers are improving; however, the
      degree to which these results are reproducible by other surgeons is less clear.
      We therefore reviewed our recent experience with total aortic arch replacement.
      METHODS: Between July 1, 1997 and July 1, 2001 19 patients underwent complete
      aortic arch replacement, with or without concomitant procedures. We
      retrospectively reviewed perioperative results retrieved from the computerized
      database and clinical records. RESULTS: The mean age of the study population was
      68 +/- 8.3 years (range 52 to 82), with women predominating (11 women, 8 men).
      All patients had hypertension. Patient history indicated active or past tobacco
      abuse in 16 patients (80%); cerebrovascular disease in 3, and peripheral vascular
      disease in 7 patients. Associated procedures included an elephant trunk in 12
      (63%), replacement of the upper descending thoracic aorta in 5 (26%), concomitant
      coronary artery bypass in 5 (26%), and aortic root replacement in 3 (16%). One
      patient underwent replacement of the entire aorta from sinotubular ridge to iliac
      bifurcation in a single procedure. Brachiocephalic reconstruction with a "Y
      graft" permitting early antegrade cerebral perfusion was performed in 12
      patients. Retrograde cerebral perfusion was performed in ten patients (53%).
      Perioperatively, death occurred in two patients (11%) and stroke in two (11%).
      CONCLUSIONS: With cautious application, techniques developed in high-volume
      centers can also achieve satisfactory results when used at centers with a more
      modest case volume.

PMID- 15151652
TI  - Long-term effectiveness of operative procedures for stanford type a aortic
      dissections.
AB  - BACKGROUND: The object was to evaluate the long-term effectiveness of strategies
      for managing the aortic root and distal aorta in type A dissections. METHODS:
      From 1990 to 1999, 50 patients (32 men (64.07%); 18 women, (36.0%); mean age 57.4
      +/- 11.1 years) underwent operation for ascending aortic dissection. Surgical
      strategies included aortic root replacement with a composite graft (21/50;
      42.0%), valve replacement with supracoronary ascending aortic graft (3/50, 6%),
      and valve preservation or repair (26/50; 52.0%). RESULTS: Overall hospital
      mortality rate was 18.0%. Follow-up was completed for 47 patients (94.0%) and
      ranged from 1 month to 10.5 years (mean 28.8 months). Actuarial survival for
      patients discharged from the hospital was 84% at 1 year, 75% at 5 years, and 66%
      at 10 years. There was no significant difference between the various procedures
      regarding mortality, neurological complications, long-term survival, and proximal
      reoperations. The ascending aorta alone was replaced in 8 of 50 patients (16%),
      ascending and hemiarch in 30 of 50 patients (60%), and arch and proximal
      descending aorta in 12 of 50 patients (24%). Hospital mortality (11.5%, 20.0%,
      and 16.7%, respectively; p > 0.05) and 5- and 10-year survival (p > 0.05) were
      not statistically dependent on the extension of the resection distally. Residual
      distal dissection was not associated with a decrease in late survival. With
      regard to emergency surgery (36/50) there was no significant difference in
      hospital mortality (p > 0.05) and 5-year survival (p > 0.05) between those who
      had undergone coronary angiography (19/36; 52.8%) on the day of surgery with
      those who had not (17/36; 47.2%). CONCLUSIONS: Preservation or repair of the
      aortic valve can be recommended in the majority of patients with type A
      dissection. Distal extension of the resection does not increase surgical risk.
      Residual distal dissection does not decrease late survival. Preoperative coronary
      angiography may not affect survival in patients undergoing emergency surgery.

PMID- 15151654
TI  - Right-sided double aortic arch in an adult.
AB  - A 27-year-old woman complained of a severe stridor caused by a right-sided double
      aortic arch with a right-sided descending thoracic aorta. A smaller left-sided
      aortic arch had an atretic segment located between the left common carotid artery
      and an aortic diverticulum from which the left subclavian artery originated.
      Through a left fourth thoracotomy, the atretic segment, which caused a
      compression of the trachea and esophagus, was ligated and divided. The ligamentum
      arteriosum could not be identified on that side. After the operation she was
      completely relieved of her symptoms.

PMID- 15151653
TI  - Charcot-Marie-Tooth syndrome and surgical management for left main coronary
      artery disease.
AB  - A 36-year-old male had coronary heart disease with a 12-year history of muscular
      weakness in his bilateral lower extremities and gait disturbance characterized by
      classical features of gastrocnemius and peroneal muscular atrophy. This is a
      clinical report of the first case of Charcot-Marie-Tooth disease (type 2)
      associated with the left main coronary artery disease requiring bypass surgery
      with cardiopulmonary bypass. The surgical procedure and postoperative course were
      uneventful. The patient was followed for 18 months postoperatively.

PMID- 15151655
TI  - Truncus arteriosus repair with double aortic homograft.
AB  - Truncus arteriosus (TA) represents 1% to 3% of congenital heart malformations and
      carries a high mortality if untreated of approximately 85% at 1 year, with almost
      half the deaths occurring during the first month of life. Significant truncal
      valve regurgitation (TVR) can be present in up to 50% of cases and reduces
      survival if persistent after surgical correction. Repair of truncal valves is a
      promising approach since growth potential and hemodynamics are maintained.
      Nevertheless this remains a technical challenge and as much as 50% of these
      valves still need to be replaced at the time of primary repair. Cryopreserved
      aortic homografts used as aortic root substitutes have provided preservation of
      excellent hemodynamic conditions as well as prevention of infectious and
      thromboembolic complications of prosthetic valves. Even if they present
      structural deterioration with time, they represent an attractive alternative to
      prosthetic valves in infants and children who would anyhow need reoperation
      because of the outgrowth of valvular or conduit substitutes.

PMID- 15151656
TI  - Compression of an extracardiac fontan following classic fontan revision.
AB  - BACKGROUND: The extracardiac Fontan arose as an alternative in order to prevent
      the classical procedure's sequelea. Complications of the extracardiac Fontan have
      been described, but this case report aims to highlight the devastating and
      infrequent complication of external conduit compression. METHODS AND RESULTS: A
      25-year-old male underwent Fontan conversion to extracardiac Fontan for atrial
      arrhythmias and giant right atrium. He developed postoperative respiratory
      distress, renal failure, and hemorrhagic pancreatitis, which prompted CT scans of
      his chest and abdomen that demonstrated external compression of the conduit by
      mediastinal hematoma. Endovascular stenting restored flow through the conduit,
      but the patient ultimately expired. CONCLUSIONS: External Fontan compression,
      which can be caused by numerous sources, may lead to significant organ
      dysfunction and can be difficult to recognize despite invasive monitoring. We
      report this complication and suggest ringed conduits to be considered to avoid
      the possibility of external compression.

PMID- 15151657
TI  - Ascending aortic endarterectomy under circulatory arrest to facilitate safe
      aortic cross-clamping in aortic valve replacement.

PMID- 15151658
TI  - Brachial artery cannulation facilitates lower ministernotomy cardiac surgery.
AB  - BACKGROUND: Lower ministernotomy has become a more popular approach for many
      heart operations. However, cannulation of the ascending aorta may cause serious
      complications. Femoral and brachial arteries have been used for alternative
      arterial cannulation sites. MATERIALS AND METHODS: The lower ministernotomy
      approach was used in 65 patients. Ascending aortic cannulation was performed in
      group 1 (n = 38), femoral cannulation in group 2 (n = 12), and brachial
      cannulation in group 3 (n = 15) patients. Brachial artery diameter was measured
      preoperatively by Doppler ultrasound in the preoperative period. RESULTS: Average
      cross-clamp time for femoral and brachial artery cannulated patients was
      significantly shorter than in patients in group 1 (31 +/- 9 and 35 +/- 6 minutes,
      respectively) (p = 0.034). Total cardiopulmonary bypass (CPB) time was 56 +/- 11
      minutes for group 1, 39 +/- 7 minutes for group 2, and 41 +/- 5.4 minutes for
      group 3 (p = 0.041). Operation time was 112 +/- 24, 88 +/- 12, and 91 +/- 11
      minutes for the groups 1, 2, and 3, respectively. There was also statistically
      significant difference between group 1 and group 3 comparisons with regard to CPB
      time (p = 0.041). Difficult exposure from many cannulas impedes access and
      lengthens the operation in group I. Superficial wound infection developed in
      seven patients in group 1, one patient in group 2, and one patient in group 3.
      CONCLUSION: Cannulation of the brachial artery is superior to the femoral due to
      possible infection and lymph leakage with the latter and both are superior to
      central cannulation when lower ministernotomy is performed. By avoiding the
      difficulties of central aortic cannula placement the operative time is decreased
      and possible wound edge is protected as lesser exposure is required.

PMID- 15151659
TI  - A simple method to prevent internal thoracic artery tension: a single pericardio
      thoracic suture technique.
AB  - Tension on the internal mammary artery is a major risk for anastomosis in
      patients with severe emphysematous lungs. For this reason, it can be necessary to
      harvest the internal thoracic artery to its origin, to skeletonize it, or as a
      last resort to use it as a free graft. Sometimes, these maneuvers cannot be
      enough to solve the problem. A simple suture technique to hang up the pericardium
      to the chest wall is described that eliminates herniation of emphysematous lungs
      across mediastinum and reduces tension on the left internal mammary artery.

PMID- 15151661
TI  - Cardiac resynchronization therapy: device-based medicine for heart failure.
AB  - Cardiac resynchronization therapy (CRT) or biventricular pacing is a novel
      adjunctive therapy for patients with advanced heart failure (HF). Many patients
      with severe HF have a left bundle branch block or an intraventricular conduction
      delay, with up to 25% of patients with a QRS > 120 ms, resulting in significant
      left ventricular (LV) dyssynchrony and a high mortality rate. The efficacy of CRT
      is based on the reduction in the conduction delay between the two ventricles and
      optimization of the ejection fraction, decrement in mitral regurgitation, LV
      remodeling, thus resulting in symptom improvement. Cardiac resynchronization
      therapy can be achieved both transvenously using a coronary sinus branch, or
      epicardially. Clinical trials have demonstrated a significant improvement in the
      NYHA class and the exercise capacity as well as a marked reduction in the
      hospitalization rate. More recently, the COMPANION trial showed a 43% reduction
      in a composite endpoint of all-cause mortality and hospitalization in the group
      receiving a CRT device in combination with an implantable cardiac defibrillator
      (ICD). Thus, management of patients with reduced LV function, wide QRS, and
      symptomatic refractory HF, despite optimal drug therapy, should include CRT as an
      option. The adjunct of an ICD combined with CRT should be considered if the LV
      ejection fraction (ischemic cardiomyopathy) is <30%. There are still significant
      unanswered questions regarding the nonresponder population and the role of tissue
      Doppler imaging techniques, the impact of CRT on total mortality and CRT in
      dilated cardiomyopathy or chronic atrial fibrillation. The use CRT
      postoperatively or at time of cardiac surgery, as well as new epicardial
      approaches using a thoracoscopic approach or robotically assisted surgery in
      patients not suitable for coronary vein leads are challenging topics to address
      in the years to come.

PMID- 15151660
TI  - Combined off-pump coronary artery bypass surgery and abdominal aorta aneurysm
      repair.

PMID- 15151663
TI  - Balloon occlusion of calcified aortic aneurysm with aortic insufficiency.

PMID- 15151662
TI  - Thinned blood, monkey lungs, and the cold heart.

PMID- 15151665
TI  - Bon sante: Is wine good for your health?

PMID- 15151666
TI  - Effects of white and red wine on endothelial function in subjects with coronary
      artery disease.
AB  - BACKGROUND: Levels of anti-oxidant polyphenols are higher in red than in white
      wine and are thought to contribute to the reduced cardiovascular risk associated
      with moderate consumption of wine observed in epidemiological studies. AIM: To
      compare the acute effects of acute ingestion of white and red wine on endothelial
      function in subjects with coronary artery disease (CAD). METHODS: Fourteen
      subjects with proven CAD were randomised to consume white and red wine with a
      light meal in a single blind cross-over study. Flow-mediated dilatation (FMD) of
      the brachial artery was measured using high-resolution ultrasonography.
      Endothelial function, lipid profile, plasma alcohol and polyphenols were measured
      at baseline, 60 and 360 min after wine consumption. RESULTS: At baseline, FMD was
      similar (white wine 1.6 +/- 1.9%, red wine 1.8 +/- 1.7%). At 360 min after
      ingestion of wine there was no difference in FMD, which improved nearly threefold
      after both wines (white wine 4.7 +/- 2.2%, red wine 3.4 +/- 2.9%; P = 0.002).
      There was no detectable change in plasma polyphenol levels after either wine.
      CONCLUSIONS: These data suggest that wine acutely improves endothelial function
      in patients with CAD. This improved endothelial function might contribute to a
      reduced risk of cardiovascular events.

PMID- 15151667
TI  - Assessment and management of inpatients with acute diabetes-related foot
      complications: room for improvement.
AB  - BACKGROUND: Australian data are currently lacking regarding management guidance,
      resource usage and outcomes of patients with diabetes requiring hospitalization
      for management of acute foot complications. AIMS: The aims of the present study
      were to review hospital admissions for diabetes-related foot complications and
      current assessment and management of these complications, and to formulate
      recommendations for future models of care. METHODS: A retrospective review of
      patient records from 1 July 1999 to 30 June 2000 was carried out. Recorded
      assessment, investigations, management, amputation rates, referral rates and
      length of hospital stay were reviewed. RESULTS: There were 69 admission episodes
      in 12 months (total patients n = 50). The mean age was 64 years, with 44 male
      patients (64%) and 25 female patients (36%). The mean diabetes duration was 11
      years (range <1-47 years). The majority of patients had type 2 diabetes.
      Assessment for known risk factors for ulceration and amputation was variable with
      history of previous ulcer/amputation recorded for 24 (35%) admissions, results of
      neurological assessment recorded for 11 (16%) and assessment of pedal pulses
      documented for 51 (74%). Glycated haemoglobin was performed during 35 (51%)
      admissions. Patients were admitted under one of 11 different inpatient units and
      the average interdepartmental referral rate was one referral per patient per
      admission. The average length of stay was 17 days, with total bed days occupied
      1163 days. Minor amputation was performed in 25 (36%) cases and major amputation
      in 8 (11%). CONCLUSIONS: Clinical assessment, investigation and management of
      this population are highly variable. This has a significant impact on the final
      clinical outcome, and changes to current processes are required to overcome the
      substantial burden of diabetic foot disease.

PMID- 15151668
TI  - High rate of complications associated with peripherally inserted central venous
      catheters in patients with solid tumours.
AB  - BACKGROUND: Peripherally inserted central catheters (PICC) have been used
      extensively as a cost-effective and safe form of medium-term intravascular
      access. There are only limited data about complications of PICC lines in oncology
      patients despite theoretical concerns about the higher risks of complications in
      these patients as a result of cancer itself and cancer therapy. AIMS: To document
      the frequency and type of PICC complications in patients with solid tumours.
      METHODS: All patients with solid tumours who were treated at Flinders Medical
      Centre, Adelaide, South Australia, Australia between January 2000 and March 2001
      were included in a retrospective review of PICC complications. RESULTS: Twenty
      seven PICC lines were inserted in 17 patients; 40.7% (11/27) of PICC lines
      developed complications requiring early removal of the PICC. Complications
      encountered were sepsis (systemic and cellulitis), thrombosis, blockage and
      leakage. Septic complications were found at a rate of 8/1000 PICC days or 25.7%
      (7/27) of PICC inserted. The median dwell time was 20 days. The mean time for a
      complication to occur was 27.5 days. CONCLUSIONS: The present study demonstrates
      a high rate of complications, which is higher than the complication rates
      reported in studies of non-oncology patients. PICC lines should be used with
      caution in patients with solid tumours. Prospective studies of the factors
      influencing the incidence of complications might be warranted.

PMID- 15151669
TI  - Can patients with dementia be assessed at a distance? The use of Telehealth and
      standardised assessments.
AB  - BACKGROUND: Telehealth could be a medium for the provision of cognitive
      assessments to distant sites. AIMS: The aims of the present study were to
      determine the interrater reliability of the Standardized Mini Mental State Exam
      (SMMSE) and the Geriatric Depression Scale (GDS) through Telehealth as compared
      to face-to-face administration. METHODS: Duplicate interviews of subjects with
      crossover of interview modality were carried out. Twenty patients were
      interviewed between two sites 11 km apart. Subjects were persons older than 65
      years (mean age 82 years) who consented to Telehealth assessments. The outcome
      measures were the differences in assessment scores between the two media.
      RESULTS: The average SMMSE score by remote assessment was 24.0 (range 11.0-30.0)
      and by direct assessment was 24.3 (range 9.0-30.0). The correlation between
      direct and remote SMMSE scores was 0.90. The mean difference between direct and
      remote SMMSE scores was -0.3 (95% confidence interval (CI): -4.6 to 4.0). In 8 of
      20 participants (40%) the difference between Telehealth and direct assessments
      was two points or more on the SMMSE. The average GDS by remote assessment was 6.1
      (range 1.0-14.0) and by direct assessment was 5.8 (range 2.0-13.0). The
      correlation between direct and remote GDS scores was 0.78. The mean difference
      between direct and remote GDS assessment was 0.3 (95% CI: -3.8 to 4.4).
      CONCLUSION: Remote assessments with SMMSE and GDS using Telehealth methods
      yielded similar results to direct assessments. However, there was a moderate
      difference between face-to-face and Telehealth assessments in some subjects,
      which could influence clinical decision-making.

PMID- 15151670
TI  - Neurological manifestations of cardiac myxoma: a review of the literature and
      report of cases.
AB  - BACKGROUND AND AIMS: Cardiac myxoma is a rare but important cause of stroke,
      which affects young people. More recently the diagnosis has been enhanced by the
      use of echocardiograms. We aimed to review the neurological presentations,
      including stroke, of cardiac myxoma in this modern era of diagnosis and
      management. METHODS: Records of patients with neurological presentations at the
      Austin and Repatriation Medical Centre and The Northern Hospital were retrieved
      from 1985 to late 2001, using International Classification of Diseases codes for
      atrial myxoma. Published literature reports were obtained by using Medline search
      database. An iterative process of bibliography review was utilised to identify
      reports not found by primary search. Case demographics, neurological
      presentations, investigations, treatment and outcome were recorded. RESULTS: From
      the Austin and Repatriation Medical Centre and The Northern Hospital, 6 cases
      were reported in detail and 107 cases from the published literature were
      analysed. The mean age of all cases was 43 (range 6-82). There was a female to
      male predominance (3:2). While there were overlapping neurological presentations,
      the most common presentation was ischaemic stroke (83% of all patients) most
      often in multiple sites (41%). The other presentations included syncope (28%),
      psychiatric presentations (23%), headache (15%) and seizures (12%). Commonest
      means of reaching the diagnosis was by echocardiography. The myxoma was
      surgically resected in 69% of cases. Of all cases, 24% were autopsy reports,
      almost all prior to availability of echocardiograms (in mid-1970s). CONCLUSIONS:
      Patients who presented with neurological complications of cardiac myxoma were
      young and stroke was by far the most common single presentation. Importantly,
      when all clinical manifestations were considered, almost half were potentially
      reversible. In recent years, echocardiography has made significant contribution
      to establishing the diagnosis less invasively. There is uncertainty about the
      role of anticoagulants. The treatment of choice remains surgical excision,
      although the timing post stroke is debatable. There is a need for large scale
      collaborative studies to help refine management strategies.

PMID- 15151672
TI  - Renal-related deaths in Australia 1997-1999.
AB  - BACKGROUND: Despite marked increases in cases of treated end-stage renal disease
      in Australia, little is known about renal disease mortality. AIMS: To quantify
      the contribution of renal diseases to mortality in Australia and to explore the
      relationship between renal disease and other common diseases as causes of death.
      METHODS: Data from the Australian Bureau of Statistics on underlying and
      associated causes of death (based on death certificates) were examined for deaths
      occurring in 1997-1999 and registered by the end of 1999. Causes of death were
      coded according to the International Classification of Diseases, 10th Revision
      (ICD-10). Several causes outside the ICD-10 chapter on diseases of the genito
      urinary system (e.g. diabetic renal disease, hypertensive renal disease and
      congenital malformations of the kidney) were included as renal. RESULTS: Of
      378,832 recorded deaths, renal disease was coded as the underlying cause for 7888
      (2.1%) and as an associated cause for an additional 28,012 (7.4%). Almost all
      renal deaths (98.4%) had at least one other cause of death recorded on the death
      certificate. CONCLUSIONS: The contribution of renal disease to Australian
      mortality has been underestimated because of historical reliance on a single
      (underlying) cause of death. Deaths involving renal disease usually occur in the
      context of multiple coexisting chronic and/or acute conditions.

PMID- 15151671
TI  - Sensitivity and specificity of serology in determining recent acute Campylobacter
      infection.
AB  - BACKGROUND: The measurement of serum antibodies to Campylobacter spp. has been
      used to investigate links between prior Campylobacter infections and the
      development of Guillain-Barre syndrome and its variants. Little is known of the
      serum antibody response to acute infections in the short- or long-term. AIMS: The
      aims of the present study were to investigate the normal serum response to an
      acute Campylobacter infection and the sensitivity and specificity of anti
      Campylobacter antibodies in determining recent Campylobacter infection. METHODS:
      An enzyme-linked immunosorbent assay (ELISA) method was used to measure serum
      anti-Campylobacter immunoglobulin G (IgG), IgA and IgM antibodies. Controls
      consisted of 420 blood donors without recent gastroenteritis, 25 patients with
      other gastrointestinal infections, 24 patients with neurological conditions not
      affecting the peripheral nerves and 19 patients with autoimmune disorders. Three
      patient groups were assessed: 99 patients with acute Campylobacter infections,
      all of whom were tested 3 weeks post-infection; 69 of these patients tested 3-6
      months later; and 74 additional patients tested >20 months post-infection.
      Western blot analysis was performed on controls and patients with high titre anti
      Campylobacter antibodies to assess for cross-reactivity and specificity. RESULTS:
      Following acute infections, all antibody classes rose in the majority of but not
      in all patients, followed by decreasing titres that did not return to baseline
      levels. Sixteen per cent of enteritis cases did not demonstrate a rise in titres
      and 9% of cases had significant levels of antibodies >20 months post-infection.
      The ELISA used was shown to be highly specific for the detection of Campylobacter
      antibodies. CONCLUSION: The use of Campylobacter-specific antibody levels as the
      sole marker of prior infection is an unreliable method of determining the
      association between Campylobacter infection and neurological disease.

PMID- 15151673
TI  - New concepts in breast cancer therapy.
AB  - Breast cancer is a common disease in the community. Its incidence is increasing
      but its mortality is falling. New therapeutic approaches based on a biological
      understanding of the disease are being investigated to improve the outcome. These
      include the areas of chemoprevention and therapy in the adjuvant and advanced
      settings, and some derive from a better understanding of the biology of breast
      cancer. New prognostic indicators are being studied to enable adjuvant
      chemotherapy to be directed towards those most likely to benefit. Trastuzumab was
      the first of the new targeted therapies to be introduced into routine practice.
      Several other agents targeting a variety of receptors and cell pathways, such as
      the epidermal growth factor receptor, the vascular epithelial growth factors and
      various intracellular tyrosine kinase mediated pathways, are under investigation.
      Increasing attention is being placed on evidence-based supportive care, both for
      control of symptoms such as hot flushes and for psychosocial problems such as
      anxiety and depression.

PMID- 15151674
TI  - Management of brain metastases.
AB  - Solid tumour brain metastases are a frequent clinical dilemma for oncologists and
      general physicians. The sound management of brain metastases requires a
      multidisciplinary approach. In this review we discuss the diagnosis and
      management of brain metastases including the role of surgery, radiotherapy, and
      chemotherapy. The standard approaches of surgical excision and primary
      radiotherapy have evolved from randomised studies. However, controversies remain
      regarding post-surgery irradiation in the setting of a solitary metastasis and
      the role of palliative chemotherapy.

PMID- 15151675
TI  - Kennedy's disease: pathogenesis and clinical approaches.
AB  - Kennedy's disease, also known as spinal and bulbar muscular atrophy, is a
      progressive degenerative condition affecting lower motor neurons. It is one of
      nine neurodegenerative disorders caused by a polyglutamine repeat expansion.
      Affecting only men, Kennedy's disease is the only one of these conditions that
      follows an X-linked mode of inheritance. The causative protein in Kennedy's
      disease, with a polyglutamine expansion residing in the first N-terminal domain,
      is the androgen receptor. Research in this field has made significant advances in
      recent years, and with the increased understanding of pathogenic mechanisms,
      feasible approaches to treatments are being investigated. In Kennedy's disease
      research, the most significant issue to emerge recently is the role of androgens
      in exacerbating the disease process. On the basis of animal experiments, a viable
      hypothesis is that higher circulating levels of androgens in men could trigger
      the degeneration of motor neurons causing this disease, and that lower levels in
      heterozygous and homozygous women are protective. This is a major issue, as
      treatment of individuals affected by Kennedy's disease with testosterone has been
      considered a reasonable therapy by some neurologists. The rationale behind this
      approach relates to the fact that Kennedy's disease is accompanied by mild
      androgen insensitivity. It was therefore believed that treatment with high doses
      of testosterone might compensate for this loss of androgen action, with the added
      benefit of preventing muscle wasting. The current review provides an overview of
      recent advances in the field of Kennedy's disease research, including approaches
      to treatment.

PMID- 15151676
TI  - Black house spiders are unlikely culprits in necrotic arachnidism: a prospective
      study.
AB  - Twenty-five patients with definite bites by Badumna spp. spiders were recruited
      prospectively. Bites occurred across Australia, 92% from October to March, and
      most during daylight. Pain occurred in all cases, was severe in seven cases, with
      a median duration of 5 min. Other effects included: puncture marks (24%),
      swelling (12%) and erythema (68%). Minor systemic effects occurred in 4 bites. No
      patient had a necrotic ulcer (0%; 97.5% confidence interval 0-14%). Black house
      spiders (Badumna spp.) are unlikely to cause necrosis, contrary to reports of
      suspected bites. Patients can be reassured and do not require any further
      investigation or treatment.

PMID- 15151677
TI  - Arm position and blood pressure: an audit.
AB  - Although arm position significantly alters blood pressure, this aspect of
      clinical behaviour has not been evaluated. Consequently, an audit of arm position
      preference involving 182 clinicians including physicians, general practitioners
      and nurses was performed. A marked variation in standing and sitting arm position
      preference, both between and within the three groups, was recorded, although
      approximately two-thirds of clinicians preferred the same arm position in the
      standing and sitting position. In particular, only 8 and 4% of clinicians chose
      the horizontal arm position in sitting and standing subjects, respectively.
      Choosing the dependent arm is a behaviour likely to lead to the overdiagnosis of
      hypertension and inappropriate treatment of hypertension because the dependent
      arm falsely elevates both systolic and diastolic blood pressure. These results
      should encourage national and international organizations to reaffirm the
      importance of the horizontal arm in the measurement of blood pressure.

PMID- 15151678
TI  - Combined anatomical and functional imaging of carcinoid metastases.

PMID- 15151679
TI  - Tackling Australia's future health problems: developing strategies to combat
      sarcopenia--age-related muscle wasting and weakness.
AB  - Some of the most serious consequences of ageing are its effects on skeletal
      muscle structure and function. Ageing is associated with a progressive loss of
      muscle mass (sarcopenia), a slowing of movement, and a decline in strength;
      factors that increase the risk of injury from sudden falls and a reliance on the
      frail elderly for assistance in accomplishing even the most basic tasks required
      for independent living. From a public health perspective, sarcopenia has
      widespread clinical implications. As the proportion of older persons in the
      population continues to grow, sarcopenia will have a dramatic impact on the lives
      of Australians and place increasing demands on health care. Although it is
      generally agreed that the deleterious effects of ageing on skeletal muscle are
      inevitable, debate exists as to whether these intrinsic changes are immutable or
      reversible. There is clearly a profound need for therapeutic strategies that can
      slow the effects of ageing on muscle function, and restore muscle size and
      strength in the frail elderly so that their quality of life can be maintained or
      improved. Physical activity plays an important role in slowing the effects of
      ageing, but exercise alone will not prevent the gradual decline in skeletal
      muscle function. Other factors, such as age-related changes in circulating levels
      of muscle anabolic hormones and growth factors, must also be considered when
      developing strategies to combat sarcopenia. Much research is needed to test the
      safety and efficacy of these exciting experimental strategies before they can be
      recommended for clinical application.

PMID- 15151680
TI  - Methysergide-induced retroperitoneal fibrosis and pericardial effusion.

PMID- 15151682
TI  - Neurosyphilis: not to be forgotten.

PMID- 15151681
TI  - Prevention of hepatotoxicity but loss of antimelanoma effect with combined
      fotemustine and anti-oxidant treatment.

PMID- 15151686
TI  - Determining the optimal concentration of fluoride in drinking water in Pakistan.
AB  - OBJECTIVES: This study was designed to determine the optimal concentrations of
      fluoride for drinking water in Pakistan. Clinical dental examination of 1020
      school children aged 12 years was carried out in 19 cities of Pakistan.
      Correlation between concentrations of water fluoride, caries and fluorosis was
      investigated by analyzing the data on fluoride concentrations in drinking water
      in the sampled population for which the caries and the fluorosis levels were also
      measured. METHODS: The optimal level of fluoride in drinking water is universally
      calculated by applying the equation of Galagan and Vermillion, which permits the
      calculation of water intake as a function of temperature. The annual mean maximum
      temperatures (AMMT) recorded during the last 5 years were collected from the
      meteorological centres of the 28 divisional headquarter stations. The average
      AMMT of Pakistan is 29 degrees C at which the optimal fluoride in drinking water
      of Pakistan was calculated to be 0.7 ppm. As drinking habits differ in various
      parts of the world, determination of optimal concentration of fluoride for
      drinking water in Pakistan was performed using a modified Galagan and Vermillion
      equation, which applies a correction factor of 0.56 to the equation. The optimal
      fluoride in drinking water in Pakistan using this modified equation was
      determined to be 0.39 ppm. RESULTS: Observation of the correlation showed that a
      fluoride concentration of 0.35 ppm in drinking water was associated with maximum
      reduction in dental caries and a 10% prevalence of fluorosis. CONCLUSIONS:
      Determining the most appropriate concentrations of fluoride in drinking water is
      crucial for communities. It is imperative that each country calculates its own
      optimal level of fluoride in drinking water based on the dose-response
      relationship of fluoride in drinking water with the levels of caries and
      fluorosis. Climatic conditions, dietary habits of the population and other
      possible fluoride exposures need to be considered in formulating these
      recommendations.

PMID- 15151685
TI  - Relationship between area deprivation and the anticaries benefit of an oral
      health programme providing free fluoride toothpaste to young children.
AB  - OBJECTIVE: To determine the effectiveness of providing free toothpaste containing
      either 1450 or 440 ppm F on caries experience in 5-year-old children living in
      areas with different levels of material deprivation. DESIGN: Five-year, examiner
      blind, randomized, controlled, parallel-group, clinical trial. Children were
      randomly assigned to three groups. SETTING: Health Districts in the north-west of
      England with high levels of dental caries. Clinical examinations were performed
      in schools during the period October 1999 to April 2000 when the children were 5
      6 years old. PARTICIPANTS: Children from 3-month birth cohorts resident in nine,
      nonfluoridated health districts. INTERVENTIONS: Toothpaste containing either 440
      or 1450 ppm F and dental health literature posted at 3-month intervals and
      toothbrush provided annually from the age of 1-5 years. Comparison group received
      no intervention. MAIN OUTCOME MEASURES: Mean dmft and proportion of participants
      with dmft > 0, dmft > or = 4, upper primary incisor caries and extraction of one
      or more primary teeth. Outcomes tabulated for quartiles of participants based on
      the distribution of the Townsend index of material deprivation. RESULTS: A total
      of 3467 children were included in the final data analysis. The Townsend index was
      found to be useful in identifying groups of children with increased caries risk.
      Overall, participants in the programme using the high-fluoride toothpaste had
      significantly (P < 0.002) less caries than the comparison group with similar
      absolute reductions in mean dmft for the most- and least-deprived groups.
      Relative to the comparison group the association between deprivation and dental
      caries was changed so that in the most-deprived quartile those using the low
      fluoride toothpaste tended to have less dental caries than the comparison group
      whereas in the least deprived they tended to have more. This difference in the
      association (slope) was statistically significant (P < 0.05). Provision of both
      low- and high-fluoride toothpaste appeared to reduce the risk of extractions for
      participants in the most-deprived quartile (P < 0.05). CONCLUSION: The relative
      benefits of the programmes supplying the two toothpastes considered in this study
      are different depending on the deprivation status of the participants. For the
      most-deprived groups postal provision of either a low- or high-fluoride
      toothpaste provides similar levels of benefit. In the less deprived groups only
      provision of the high-fluoride toothpaste provided a benefit. The absolute caries
      reduction seen for provision of the high-fluoride toothpaste was not related to
      the deprivation status and hence the programme did not reduce deprivation-related
      health inequalities. Targeting the programme using the methods employed in this
      study is unlikely to improve the effectiveness of the programme.

PMID- 15151687
TI  - The effectiveness of a 6-year oral health education programme for primary
      schoolchildren.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a 6-year oral
      health education programme in primary schoolchildren. METHODS: This programme was
      part of the Signal-Tandmobiel project, a longitudinal collaborative project
      combining the registration of oral health data and oral health promotion. The
      intervention group comprised 3291 children with a mean age of 7.1 years (SD 0.43)
      at the start of the programme. Every year these children were examined clinically
      and a questionnaire, to be filled in by the parents, was administered to assess
      oral health behaviour. These children received an oral health education programme
      which consisted of a yearly 1-h instruction. Data collected using the same
      questionnaire and clinical examination in 676 12-year-old children were included
      as control group. The samples were obtained using stratified cluster sampling.
      The effect of the interventional programme was assessed by measuring differences
      in caries prevalence and incidence, levels of dental care and reported oral
      health behaviour. RESULTS: Mean DMFT/S values, although higher in the control
      group, were not significantly different. The reported frequency of brushing was
      the same in both groups. Significant differences in favour of the intervention
      group were found in the number of between-meal snacks (P < 0.001) and the proper
      use of topical fluorides (P < 0.05). Children in the control group showed a
      significantly lower proportion of filled teeth than those in the intervention
      group (P < 0.01), with a care index of 73% versus 80%. CONCLUSION: In conclusion,
      the implemented minimal school-based oral health education programme did not
      result in a significant reduction of the caries prevalence measured. The
      programme has been effective in improving reported dietary habits and the proper
      use of topical fluorides and resulted in a higher care index.

PMID- 15151688
TI  - The utility of the zero-inflated Poisson and zero-inflated negative binomial
      models: a case study of cross-sectional and longitudinal DMF data examining the
      effect of socio-economic status.
AB  - OBJECTIVES: To examine the utility of the zero-inflated Poisson (ZIP) and zero
      inflated negative binomial (ZINB) modelling approaches for modelling four sets of
      dental caries data from the same cohort study [with particular attention to the
      influence of childhood socioeconomic status (SES)]: cross-sectional data on the
      deciduous dentition at age 5 years; cross-sectional data on the permanent
      dentition at age 18 and 26 years; and longitudinal data on caries increment
      between ages 18 and 26 years. METHODS: Data on dental caries occurrence at ages
      5, 18 and 26 years were obtained from the Dunedin Multidisciplinary Health and
      Development Study (DMHDS). ZIP and ZINB models were fitted to the cross-sectional
      (n = 745) and longitudinal (n = 809) data sets using Stata (Intercooled Stata
      7.0). The dependent variables for the three cross-sectional analyses were the
      DMFS indices at age 5, 18, and 26 years, and net DFS increment (NETDFS) was the
      dependent variable for the longitudinal analysis. RESULTS: The empty ZIP model
      was a poor fit for all four data sets, whereas the empty ZINB model showed good
      fit; consequently both the cross-sectional and longitudinal analyses were
      conducted using ZINB modelling. Being in the high-SES group during childhood was
      associated with a greater probability of being caries-free by age 18 years, over
      and above that which would be expected from the negative binomial process. Low
      childhood SES also had the largest coefficient in the modelling of the negative
      binomial process, but at age 5 years, where the adjusted mean dmfs score in the
      low-SES group was 6.8 (compared with 4.7 and 2.9 in the medium- and high-SES
      groups, respectively). The substantial SES differences which existed at age 5
      years (in the deciduous dentition) had reduced somewhat by age 18 years, and had
      widened again by age 26 years. In the longitudinal analysis, "baseline" caries
      experience (age 18-year DMFS) was a predictor both of being an extra zero and of
      caries severity. CONCLUSION: This investigation of the utility of the zero
      inflated approach for modelling both cross-sectional and longitudinal caries data
      has shown that ZIP/ZINB models can provide new insight into disease patterns. It
      is anticipated that they will become increasingly useful in epidemiological
      studies that use the DMF index as the outcome measure.

PMID- 15151689
TI  - Self-care intervention to reduce oral candidiasis recurrences in HIV-seropositive
      persons: a pilot study.
AB  - OBJECTIVES: This single-blind randomized controlled pilot study evaluated the
      efficacy of a behavioral intervention program, PRO-SELF: Candidiasis, to reduce
      time to recurrence of oral candidiasis over 6 months in susceptible HIV
      seropositive persons. The intervention involved instruction by dentists on
      improving oral hygiene, minimizing sugar intake, and self-diagnosing candidiasis.
      METHODS: Participants were adults with oral candidiasis responsive to antifungals
      who presented to the UCSF Stomatology Clinic between 1997 and 2000. At 2-3 weeks
      of follow-up visits, a dentist "examiner", masked to group assignment, quizzed
      participants as to the presence of candidiasis, and assessed candidiasis status.
      A second, unmasked dentist "instructor" then delivered the program to
      intervention participants. Participants recorded dietary and oral hygiene
      practices in 24-h recall diaries: intervention participants at each visit and
      controls at initial and final visits. RESULTS: At randomization, CD4+ cell counts
      (cells/mm(3)) were 298 +/- 188 among 18 intervention participants and 396 +/- 228
      among 17 controls. The candidiasis recurrence rates at 6 months were 78% among
      intervention compared with 88% among control participants (hazard ratio 0.72; 95%
      CI 0.35-1.50). Performing oral hygiene after meals/snacks showed the largest
      relative improvement: intervention-control difference in proportion of
      meals/snacks affected was 24% (95% CI -1 to 48%). Self-diagnoses of candidiasis
      were inaccurate, possibly because of mild episodes. CONCLUSIONS: The results
      weakly indicate that regular instruction from healthcare professionals helps
      patients delay candidiasis recurrence by improving oral hygiene. Among HIV
      seropositive persons, those with poor oral hygiene, and high-sugar diets are most
      likely to benefit.

PMID- 15151690
TI  - A longitudinal study of caries onset in initially caries-free children and
      baseline salivary mutans streptococci levels: a Kaplan-Meier survival analysis.
AB  - OBJECTIVES: To apply survival analysis to a longitudinal study of the
      relationship between salivary mutans streptococci (MS) levels at baseline in
      initially caries-free children and caries onset in deciduous, mixed, and
      permanent dentition. METHODS: The Kaplan-Meier survival analysis method was used
      to compare survival times to caries onset for initially caries-free children with
      low levels of MS at baseline with survival times to caries onset for initially
      caries-free children with high levels of MS at baseline. RESULTS: Data from a 6
      year longitudinal study of caries risk in initially caries-free children in
      Rochester and the Finger Lakes Region of western New York were utilized for this
      study. Of 464 children analyzed, 327 had a low level of MS and 137 had a high
      level of MS at baseline. Survival analyses showed that children with a low level
      of MS at baseline remained caries-free for a longer period than children with a
      high level of MS at baseline. Statistically significant relationships [hazard
      ratios (HR)] with onset of caries in deciduous, mixed and permanent teeth were
      found with high and low levels of salivary MS. CONCLUSIONS: Based on our
      analysis, we concluded that children who were caries-free at baseline and who had
      high salivary MS levels at baseline would be at greater risk, i.e. more
      susceptible to caries onset, at any given time than caries-free children who had
      low salivary MS levels at baseline. Survival functions for deciduous, mixed and
      permanent dentitions with their 95% confidence limits have been calculated.
      Survival analysis for the exploration of longitudinal caries studies has an
      advantage over traditional statistical methods, as it takes into account censored
      observations and incorporates the concept of risk over time. Hence, survival
      analysis is well suited for studying transitions from one health state to
      another, in this case, from a caries-free state to a caries-active state.

PMID- 15151691
TI  - Willingness to pay for dentin regeneration in a sample of dentate adults.
AB  - OBJECTIVES: Measurement of individuals' valuation of dental treatments is
      important in the evaluation of new technologies. In this paper the value of
      dentin regeneration, a new treatment for teeth with reversible pulpitis, is
      measured based on what individuals say they would be willing to pay to receive
      the treatment. METHODS: A total of 611 randomly selected dentate adults answered
      willingness to pay (WTP) and dental insurance questions. Detailed descriptions of
      the process and expected outcomes for dentin regeneration were presented to
      subjects as part of a larger study measuring preferences for different
      treatments. WTP was determined for two different levels of success for dentin
      regeneration. RESULTS: At a success rate of 95%, the mean WTP for dentin
      regeneration was $262.70 (noninsured) and $11.00 per month (insured subjects).
      For success rate of 75%, the corresponding values were $210.90 and $9.20 per
      month. Multivariate analyses were used to identify any significant relationships
      between WTP and a range of variables covering socio-demographic, socio-economic,
      dental experience and oral health status variables. The findings indicate that
      individuals' valuations of treatments involve substantial unexplained variation.
      About half of the noninsured subjects would pay for dentin regeneration if it
      cost $200 per tooth. CONCLUSIONS: The data on the WTP for dentin regeneration
      indicate that a substantial percentage of adults will pay for this new
      technology. This study provides for the first time an estimate of WTP for dentin
      regeneration among the population.

PMID- 15151692
TI  - A meta-analysis of the prevalence of dental agenesis of permanent teeth.
AB  - OBJECTIVE: To gain more insight into the prevalence of dental agenesis. METHODS:
      Data from Caucasian populations in North America, Australia and Europe were
      included in a meta-analysis. For the prevalence of African American, Chinese and
      Arab groups only indications could be reported because of a limited number of
      studies. RESULTS: Agenesis differs by continent and gender: the prevalence for
      both sexes was higher in Europe (males 4.6%; females 6.3%) and Australia (males
      5.5%; females 7.6%) than for North American Caucasians (males 3.2%; females
      4.6%). In addition, the prevalence of dental agenesis in females was 1.37 times
      higher than in males. The mandibular second premolar was the most affected tooth,
      followed by the maxillary lateral incisor and the maxillary second premolar. The
      occurrence of dental agenesis was divided into three main groups: common (P2(i) >
      I2(s) > P2(s)), less common (I1(i) > I2(i) & P1(s) > C(s) & M2(i)) and rare
      (M2(s) & M1(s) > C(i) > M1(i) & I1(s)). Unilateral occurrence of dental agenesis
      is more common than bilateral occurrence. However, bilateral agenesis of
      maxillary lateral incisors is more common than unilateral agenesis. The overall
      prevalence of agenesis in the maxilla is comparable with that in the mandible,
      but a marked difference was found between both jaws regarding tooth type. Absence
      of one or two permanent teeth is found in 83% of the subjects with dental
      agenesis. A practical application of the results of the meta-analysis is the
      estimation of dental treatment need.

PMID- 15151693
TI  - The effect of pre-operative information in relieving anxiety in oral surgery
      patients.
AB  - Appropriate stress management of patients is essential for smooth running of
      invasive or surgical dental procedures conducted under local anaesthesia.
      OBJECTIVE: The current study analysed the effectiveness of pre-operative
      information provision for anxiety reduction during dentoalveolar surgery in
      patients with high- or low-trait anxiety. METHODS: Patients scheduled for oral
      surgical procedures performed by six private dental practitioners were invited to
      participate in the study. They were randomly assigned to four groups and received
      the following pre-operative information: (i) basic information only, (ii) basic
      information with details of the operative procedures, (iii) basic information
      with details of the expected recovery, and (iv) basic information with details of
      both the operative procedures and recovery. The participants' trait anxiety level
      was measured with the Depression Anxiety Stress Scales (DASS), then they were
      divided into high- or low-trait anxiety groups with the method of median-split on
      the basis of the DASS score. Self-rated anxiety was recorded immediately before,
      during and 10 min after the surgical procedures. RESULTS: High-trait anxiety
      subjects gave higher self-reported anxiety levels (repeated-measures ANOVA, P <
      0.05). Pre-operative provision of details about the expected recovery only or
      details concerning both the operative procedures and recovery led to significant
      reduction in self-reported anxiety among the participants throughout the
      procedure (P < 0.01). However, information on operative procedures led to anxiety
      reduction in low (P < 0.05) but not high-trait anxiety participants. CONCLUSION:
      Provision of pre-operative information of the recovery process leads to
      significant anxiety reduction in all patients who undergo surgical/invasive
      procedures with local anaesthesia.

PMID- 15151695
TI  - Spotting effect in microarray experiments.
AB  - BACKGROUND: Microarray data must be normalized because they suffer from multiple
      biases. We have identified a source of spatial experimental variability that
      significantly affects data obtained with Cy3/Cy5 spotted glass arrays. It yields
      a periodic pattern altering both signal (Cy3/Cy5 ratio) and intensity across the
      array. RESULTS: Using the variogram, a geostatistical tool, we characterized the
      observed variability, called here the spotting effect because it most probably
      arises during steps in the array printing procedure. CONCLUSIONS: The spotting
      effect is not appropriately corrected by current normalization methods, even by
      those addressing spatial variability. Importantly, the spotting effect may alter
      differential and clustering analysis.

PMID- 15151696
TI  - ACE2 gene expression is up-regulated in the human failing heart.
AB  - BACKGROUND: ACE2 is a novel homologue of angiotensin converting enzyme (ACE).
      ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an
      essential regulator of cardiac function in vivo. Since overactivity of the renin
      angiotensin system contributes to the progression of heart failure, this
      investigation assessed changes in gene expression of ACE2, ACE, AT1 receptor and
      renin in the human failing heart. METHODS: The sensitive technique of
      quantitative reverse transcriptase polymerase chain reaction was used to
      determine the level of mRNA expression of ACE and ACE2 in human ventricular
      myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated
      cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following
      logarithmic transformation of the data, a one-way analysis of variance was
      performed for each target gene followed by a Dunnett's test to compare the two
      disease groups IDC and ICM versus control. RESULTS: As anticipated, ACE mRNA was
      found to be significantly increased in the failing heart with a 3.1 and 2.4-fold
      up-regulation found in IDC and ICM relative to non-diseased myocardium.
      Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold
      increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change
      in angiotensin AT1 receptor mRNA expression was found in failing myocardium and
      renin mRNA was not detected. CONCLUSIONS: These data suggest that ACE2 is up
      regulated in human IDC and ICM and are consistent with the hypothesis that
      differential regulation of this enzyme may have important functional consequences
      in heart failure. This strengthens the hypothesis that ACE2 may be a relevant
      target for the treatment of heart failure and will hopefully spur further studies
      to clarify the functional effects in human myocardium of ACE2 derived peptides.

PMID- 15151697
TI  - Long term physiologic modification using rAAV in utero gene-therapy.
AB  - BACKGROUND: Transfer of genes in utero via the amniotic fluid was shown
      previously with recombinant adeno-associated viruses (rAAV) to be highly
      efficient. Expression for over one year was demonstrated using reporter genes. In
      addition, it was shown previously that transgenes delivered by this method
      release protein into the general circulation. Given these results experiments
      were designed to test the hypothesis that in utero rAAV gene therapy could result
      in long term physiologic modification. METHODS: A rAAV recombinant expressing
      ciliary neurotrophic factor (cntf) and green fluorescent (gfp) in a polycistronic
      messenger was used to treat rat fetuses in utero. CNTF causes weight loss and
      decreased water consumption as a measurable physiologic effect. GFP was used as a
      marker of gene expression. RESULTS: In utero gene transfer with rAAV carrying
      human cntf and gfp resulted in long-term gene expression in rat. CNTF-specific
      physiologic effects of a decrease in weight and water intake were obtained.
      Expression of the GFP was documented in the treated animals at one year of age.
      CONCLUSION: Given this data, in utero gene therapy with rAAV into multipotential
      stem cells resulted in long term systemic physiologic modification of the treated
      animals by the transgene product. In utero rAAV gene therapy potentially could be
      used for gene replacement therapy in metabolic disorders.

PMID- 15151698
TI  - "Harnessing genomics to improve health in India" - an executive course to support
      genomics policy.
AB  - BACKGROUND: The benefits of scientific medicine have eluded millions in
      developing countries and the genomics revolution threatens to increase health
      inequities between North and South. India, as a developing yet also
      industrialized country, is uniquely positioned to pioneer science policy
      innovations to narrow the genomics divide. Recognizing this, the Indian Council
      of Medical Research and the University of Toronto Joint Centre for Bioethics
      conducted a Genomics Policy Executive Course in January 2003 in Kerala, India.
      The course provided a forum for stakeholders to discuss the relevance of genomics
      for health in India. This article presents the course findings and
      recommendations formulated by the participants for genomics policy in India.
      METHODS: The course goals were to familiarize participants with the implications
      of genomics for health in India; analyze and debate policy and ethical issues;
      and develop a multi-sectoral opinion leaders' network to share perspectives. To
      achieve these goals, the course brought together representatives of academic
      research centres, biotechnology companies, regulatory bodies, media, voluntary,
      and legal organizations to engage in discussion. Topics included scientific
      advances in genomics, followed by innovations in business models, public sector
      perspectives, ethics, legal issues and national innovation systems. RESULTS:
      Seven main recommendations emerged: increase funding for healthcare research with
      appropriate emphasis on genomics; leverage India's assets such as traditional
      knowledge and genomic diversity in consultation with knowledge-holders;
      prioritize strategic entry points for India; improve industry-academic interface
      with appropriate incentives to improve public health and the nation's wealth;
      develop independent, accountable, transparent regulatory systems to ensure that
      ethical, legal and social issues are addressed for a single entry, smart and
      effective system; engage the public and ensure broad-based input into policy
      setting; ensure equitable access of poor to genomics products and services;
      deliver knowledge, products and services for public health. A key outcome of the
      course was the internet-based opinion leaders' network - the Indian Genome Policy
      Forum - a multi-stakeholder forum to foster further discussion on policy.
      CONCLUSION: We expect that the process that has led to this network will serve as
      a model to establish similar Science and Technology policy networks on regional
      levels and eventually on a global level.

PMID- 15151700
TI  - Mosquito appetite for blood is stimulated by Plasmodium chabaudi infections in
      themselves and their vertebrate hosts.
AB  - BACKGROUND: Arthropod vectors of disease may encounter more than one infected
      host during the course of their lifetime. The consequences of super-infection to
      parasite development are rarely investigated, but may have substantial
      epidemiological and evolutionary consequences. METHODS: Using a rodent malaria
      model system, behavioural avoidance of super-infection was tested by examining
      whether already-infected Anopheles stephensi mosquitoes were less responsive to
      new vertebrate hosts if they were infected. Additionally, a second dose of
      parasites was given to malaria-infected mosquitoes on a biologically realistic
      time scale to test whether it impeded the development of a first infection.
      RESULTS: No effect of a second infected blood meal on either the prevalence or
      parasite burden arising from a first was found. Furthermore, it was found that
      not only were infected mosquitoes more likely to take a second blood meal than
      their uninfected counterparts, they were disproportionately drawn to infected
      hosts. CONCLUSIONS: The alterations in mosquito feeding propensity reported here
      would occur if parasites have been selected to make infected vertebrate hosts
      more attractive to mosquitoes, and infected mosquitoes are more likely to seek
      out new blood meals. Although such a strategy might increase the risk of super
      infection, this study suggests the cost to parasite development is not high and
      as such would be unlikely to outweigh the potential benefits of increasing the
      contact rate between the parasite's two obligate hosts.

PMID- 15151699
TI  - Percutaneous closure of interatrial communications in adults - prospective
      embolism prevention study with two- and three-dimensional echocardiography.
AB  - BACKGROUND: Patients with interatrial communications after paradoxical embolic
      events are at risk for recurrent thromboembolism. We hypothesized that
      transcatheter closure of the defects would result in long-term prevention of
      systemic embolism and performed clinical and echocardiographic follow-up.
      METHODS: We included 161 patients (mean age 46.8 +/- 11 years, 83 females) with
      patent foramen ovale or atrial septal defect and at least one documented
      paradoxical systemic thrombembolic event and/or a large atrial shunting. RESULTS:
      The implantation procedure was successfully performed without major complications
      in all patients and minor complications in 2.5%. Two and / or three dimensional
      echocardiography was performed before and after 4 weeks and 12 months using a
      multiplane transoesophageal probe. After 4 weeks and 6 months two patients had
      minimal shunting. These residual defects were closed with a second device
      implantation without shunting after further 4 weeks. During a follow-up of 324.3
      patient years (range, 13 to 19 months), recurrent embolic events occurred in only
      1 patient (0.6%). CONCLUSION: After primary paradoxical systemic embolism,
      results of transcatheter occlusion of the interatrial communications are
      dependent on the closure device system and can prevent further secondary embolic
      events for up to 1 year after the percutaneous closure. Three dimensional
      echocardiography provides dynamic features of the defects and the post closure
      status and may lead to an improved understanding and diagnosis of the interatrial
      defect.

PMID- 15151702
TI  - Does knowledge of cancer diagnosis affect quality of life? A methodological
      challenge.
AB  - BACKGROUND: As part of an assessment of quality of life in lung cancer patients
      an investigation was carried out to examine whether the knowledge of their
      diagnosis affected their quality of life. METHODS: Every patient in a defined
      geographical area with a potential diagnosis of lung cancer was interviewed at
      first consultation and after a definitive treatment has been given. Quality of
      life was assessed using three standard measures: the Nottingham Health Profile
      (NHP), the EORTC quality of life questionnaire (QLQ-C30) and its lung cancer
      supplementary questionnaire (QLQ-LC13). Comparison was made in quality of life
      scores between patients who knew their cancer diagnosis and those who did not.
      RESULTS: In all, 129 lung cancer patients were interviewed. Of these, 30 patients
      (23%) knew and 99 (78%) did not know their cancer diagnosis at the time of
      baseline assessment. The patient groups were similar in their characteristics
      except for age (P = 0.04) and cell type (P < 0.0001). Overall, there were no
      significant differences between these two groups with regard to their scores on
      the three instruments used. A major finding was that both group scored almost the
      same on emotional reactions (P = 0.8) and social isolation (P = 1.0) as measured
      by the NHP, and emotional (P = 0.7) and social functioning (P = 1.0) as measured
      by the EORTC QLQ-C30. In addition there were no significant differences in
      patients' symptom scores between those who knew their diagnosis and those who did
      not, nor did any consistent pattern emerge. The only significant difference was
      for sleep difficulties (P = 0.02). CONCLUSION: The findings suggest that the
      knowledge of cancer diagnosis does not affect the way in which patients respond
      to quality of life questionnaires.

PMID- 15151701
TI  - Profiling quality of care: Is there a role for peer review?
AB  - BACKGROUND: We sought to develop a more reliable structured implicit chart review
      instrument for use in assessing the quality of care for chronic disease and to
      examine if ratings are more reliable for conditions in which the evidence base
      for practice is more developed. METHODS: We conducted a reliability study in a
      cohort with patient records including both outpatient and inpatient care as the
      objects of measurement. We developed a structured implicit review instrument to
      assess the quality of care over one year of treatment. 12 reviewers conducted a
      total of 496 reviews of 70 patient records selected from 26 VA clinical sites in
      two regions of the country. Each patient had between one and four conditions
      specified as having a highly developed evidence base (diabetes and hypertension)
      or a less developed evidence base (chronic obstructive pulmonary disease or a
      collection of acute conditions). Multilevel analysis that accounts for the nested
      and cross-classified structure of the data was used to estimate the signal and
      noise components of the measurement of quality and the reliability of implicit
      review. RESULTS: For COPD and a collection of acute conditions the reliability of
      a single physician review was quite low (intra-class correlation = 0.16-0.26) but
      comparable to most previously published estimates for the use of this method in
      inpatient settings. However, for diabetes and hypertension the reliability is
      significantly higher at 0.46. The higher reliability is a result of the reviewers
      collectively being able to distinguish more differences in the quality of care
      between patients (p < 0.007) and not due to less random noise or individual
      reviewer bias in the measurement. For these conditions the level of true quality
      (i.e. the rating of quality of care that would result from the full population of
      physician reviewers reviewing a record) varied from poor to good across patients.
      CONCLUSIONS: For conditions with a well-developed quality of care evidence base,
      such as hypertension and diabetes, a single structured implicit review to assess
      the quality of care over a period of time is moderately reliable. This method
      could be a reasonable complement or alternative to explicit indicator approaches
      for assessing and comparing quality of care. Structured implicit review, like
      explicit quality measures, must be used more cautiously for illnesses for which
      the evidence base is less well developed, such as COPD and acute, short-course
      illnesses.

PMID- 15151703
TI  - Microarray analysis in clinical oncology: pre-clinical optimization using needle
      core biopsies from xenograft tumors.
AB  - BACKGROUND: DNA microarray profiling performed on clinical tissue specimens can
      potentially provide significant information regarding human cancer biology.
      Biopsy cores, the typical source of human tumor tissue, however, generally
      provide very small amounts of RNA (0.3-15 microg). RNA amplification is a common
      method used to increase the amount of material available for hybridization
      experiments. Using human xenograft tissue, we sought to address the following
      three questions: 1) is amplified RNA representative of the original RNA profile?
      2) what is the minimum amount of total RNA required to perform a representative
      amplification? 3) are the direct and indirect methods of labeling the
      hybridization probe equivalent? METHODS: Total RNA was extracted from human
      xenograft tissue and amplified using a linear amplification process. RNA was
      labeled and hybridized, and the resulting images yielded data that was extracted
      into two categories using the mAdb system: "all genes" and "outliers". Scatter
      plots were generated for each slide and Pearson Coefficients of correlation were
      obtained. RESULTS: Results show that the amplification of 5 microg of total RNA
      yields a Pearson Correlation Coefficient of 0.752 (N = 6,987 genes) between the
      amplified and total RNA samples. We subsequently determined that amplification of
      0.5 microg of total RNA generated a similar Pearson Correlation Coefficient as
      compared to the corresponding original RNA sample. Similarly, sixty-nine percent
      of total RNA outliers were detected with 5 microg of amplified starting RNA, and
      55% of outliers were detected with 0.5 microg of starting RNA. However,
      amplification of 0.05 microg of starting RNA resulted in a loss of fidelity
      (Pearson Coefficient 0.669 between amplified and original samples, 44% outlier
      concordance). In these studies the direct or indirect methods of probe labeling
      yielded similar results. Finally, we examined whether RNA obtained from needle
      core biopsies of human tumor xenografts, amplified and indirectly labeled, would
      generate representative array profiles compared to larger excisional biopsy
      material. In this analysis correlation coefficients were obtained ranging from
      0.750-0.834 between U251 biopsy cores and excised tumors, and 0.812-0.846 between
      DU145 biopsy cores and excised tumors. CONCLUSION: These data suggest that needle
      core biopsies can be used as reliable tissue samples for tumor microarray
      analysis after linear amplification and either indirect or direct labeling of the
      starting RNA.

PMID- 15151704
TI  - Comprehensive Geriatric Assessment (CGA) in general practice: results from a
      pilot study in Vorarlberg, Austria.
AB  - BACKGROUND: Most comprehensive geriatric assessment (CGA) programs refer to
      hospital-based settings. However the body of geriatric healthcare is provided by
      general practitioners in their office. Structured geriatric problem detection by
      means of assessment instruments is crucial for efficient geriatric care giving in
      the community. METHODS: We developed and pilot tested a German language geriatric
      assessment instrument adapted for general practice. Nine general practices in a
      rural region of Austria participated in this cross-sectional study and
      consecutively enrolled 115 persons aged over 75 years. The prevalence of specific
      geriatric problems was assessed, as well as the frequency of initiated procedures
      following positive and negative tests. Whether findings were new to the physician
      was studied exemplarily for the items visual and hearing impairment and
      depression. The acceptability was recorded by means of self-administered
      questionnaires. RESULTS: On average, each patient reported 6.4 of 14 possible
      geriatric problems and further consequences resulted in 43.7% (27.5% to 59.8%) of
      each problem. The items with either the highest prevalence and/or the highest
      number of initiated actions by the GPs were osteoporosis risk, urinary
      incontinence, decreased hearing acuity, missing pneumococcal vaccination and fall
      risk. Visual impairment was newly detected in only 18% whereas hearing impairment
      and depression was new to the physician in 74.1% and 76.5%, respectively.A
      substantial number of interventions were initiated not only following positive
      tests (43.7% per item; 95% CI 27.5% to 59.8%), but also as a consequence of
      negative test results (11.3% per item; 95% CI 1.7% to 20.9%). The mean time
      expenditure to accomplish the assessment was 31 minutes (SD 10 min). Patients
      (89%) and all physicians confirmed the CGA to provide new information in general
      on the patient's health status. All physicians judged the CGA to be feasible in
      everyday practice. CONCLUSION: This adapted CGA was feasible and well accepted in
      the general practice sample. High frequencies of geriatric problems were detected
      prompting high numbers of problem-solving initiatives. But a substantial number
      of actions of the physicians following negative tests point to the risks of too
      aggressive treatment of elderly patients with possibly subsequent negative
      effects.

PMID- 15151705
TI  - The association between air travel and deep vein thrombosis: systematic review &
      meta-analysis.
AB  - BACKGROUND: Air travel has been linked with the development of deep vein
      thrombosis (DVT) since the 1950s with a number of plausible explanations put
      forward for causation. No systematic review of the literature exploring this
      association has previously been published. METHODS: A comprehensive search was
      undertaken (Data bases searched were: MEDLINE, EMBASE, Cochrane Library) for
      studies that estimated both the incidence and the risk of DVT in air travellers
      relative to non-air travellers. RESULTS: In total 254 studies were identified but
      only six incidence studies and four risk studies met inclusion criteria
      justifying their use in a systematic review. Incidence of symptomatic DVT ranged
      from (0%) in one study to (0.28%) which was reported in pilots over ten years.
      The incidence of asymptomatic DVT ranged from (0%) to (10.34%). Pooled odds
      ratios for the two case control studies examining the risk of DVT following air
      travel were 1.11 (95% CI: 0.64-1.94). Pooled odds ratios for all models of travel
      including two studies of prolonged air travel (more than three hours) were 1.70
      (95% CI: 0.89-3.22). CONCLUSION: We found no definitive evidence that prolonged
      (more than 3-hours) travel including air travel, increases the risk of DVT. There
      is evidence to suggest that flights of eight hours or more increase the risk of
      DVT if additional risk factors exist.

PMID- 15151706
TI  - Quinone oxidoreductase (NQO1) gene polymorphism (609C/T) may be associated with
      tardive dyskinesia, but not with the development of schizophrenia.
AB  - The association between the quinone oxidoreductase gene (NQO1) polymorphism
      (609C/T) and schizophrenia was examined to replicate and extend the findings of a
      previous study (Hori et al., 2003). The study sample was 107 schizophrenia in
      patients and 106 healthy controls. The distributions of the NQO1 genotypes and
      alleles were not different between the schizophrenia patients and the controls.
      However, the frequency of the variant genotype was significantly higher in the
      subgroup with tardive dyskinesia (TD) than in the subgroup without (p=0.019). The
      subjects with allele T were significantly more frequent in the TD patients than
      in those without (odds ratio 2.256, 95% confidence interval 1.235-4.133). In
      addition, the Abnormal Involuntary Movement Scale (AIMS) score was significantly
      higher in the variant genotype group (T/T) than in other genotypic groups (C/C
      and C/T) (p=0.004). This study suggests that the NQO1 gene polymorphism (609C/T)
      may confer susceptibility to the development of TD in schizophrenia, at least in
      the Korean population.

PMID- 15151708
TI  - Haploidization to produce human embryos: a new frontier for micromanipulation.

PMID- 15151709
TI  - A specific programme of gene transcription in male germ cells.
AB  - The differentiation of male germ cell requires spermatogenic stage and cell
      specific gene expression that is achieved by unique chromatin remodelling,
      transcriptional control, and the expression of testis-specific genes or isoforms.
      Specialized transcription complexes that coordinate the differentiation programme
      of spermatogenesis have been found in germ cells, which display specific
      differences in the components of the general transcription machinery. The TATA
      binding (TBP) protein family and its associated co-factors, for example, show
      upregulated expression in testis. In this physiological context, transcriptional
      control mediated by the activator CREM represents an established paradigm. In
      somatic cells, activation by CREM requires its phosphorylation at a unique
      regulatory site (Ser117) and subsequent interaction with the ubiquitous
      coactivator CBP. In testis, CREM transcriptional activity is controlled through
      interaction with a tissue-specific partner, ACT, which confers a powerful,
      phosphorylation-independent activation capacity. The function of ACT is regulated
      by a testis-specific kinesin, KIF17b. This study discusses some aspects of the
      testis-specific transcription machinery, the function of which is essential for
      the process of spermatogenesis.

PMID- 15151710
TI  - Reprogramming of epigenetic inheritance by somatic cell nuclear transfer.
AB  - Somatic cloning by nuclear transfer returns a differentiated cell to a totipotent
      stage, a process termed nuclear reprogramming. During this de-differentiation
      process, genes inactivated during tissue differentiation are re-activated in a
      temporal and spatial special manner. It is believed that tissue differentiation
      occurs through epigenetic mechanisms, genetic inheritance that does not involve
      changes in DNA sequences. Developmental abnormalities and a high mortality rate
      in cloned offspring have frequently been observed and probably result from
      incomplete nuclear reprogramming. In this review, the reprogramming of two
      epigenetic mechanisms, imprinting and X chromosome inactivation, as well as
      recent attempts to modify pre-existing epigenetic marks in donor cells to improve
      nuclear transfer efficacy, are discussed.

PMID- 15151711
TI  - Implications of cloning technique for reproductive medicine.
AB  - The birth of Dolly following the transfer of mammary gland nuclei into enucleated
      eggs established cloning as a feasible technique in mammals, but the moral
      implications and high incidence of developmental abnormalities associated with
      cloning have induced the majority of countries to legislate against its use with
      human gametes. Because of such negative connotations, restrictive political
      reactions could jeopardize the therapeutic and scientific promise that certain
      types of cloning may present. For example, in addition to its proposed use as a
      way of generating stem cells, the basic technique of nuclear transplantation has
      proven useful in other ways, including its application to immature eggs as a new
      approach to the prevention of the aneuploidy common in older women, and for some
      recent advances in preimplantation genetic diagnosis. Thus, while attempts at
      reproductive cloning in man would seem premature and even dangerous at present,
      this field will require rational rather than emotional reactions as a basis for
      legislation if the therapeutic promise of stem cell research and the experimental
      potential of nuclear transplantation techniques are to be fully realized.

PMID- 15151712
TI  - Concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid
      and serum in relation to stimulation protocol and outcome of assisted
      reproduction treatment.
AB  - In this prospective, randomized study, concentrations of gonadotrophins and
      steroids in pre-ovulatory follicular fluid (FF) and serum were related to type of
      stimulation protocol as well as to the outcome of assisted reproduction in 280
      women subjected to the long protocol gonadotrophin-releasing hormone (GnRH)
      agonist pituitary down-regulation and ovarian stimulation with either human
      menopausal gonadotrophin (HMG) or recombinant FSH. In the women treated with HMG,
      concentrations of LH, FSH, oestradiol and androstenedione in FF were
      significantly higher, and those of human chorionic gonadotrophin (HCG) and
      progesterone significantly lower, than in the women treated with recombinant FSH
      (rFSH). More women became pregnant and delivered in the HMG than in the rFSH
      group. These differences, however, were not statistically significant.
      Concentrations of FSH in serum and of FSH and LH in FF were significantly higher
      in conception than in non-conception cycles, whereas all other hormone
      concentrations in FF and serum were similar. The present study demonstrates that
      the pre-ovulatory follicular fluid hormone profile is significantly influenced by
      the gonadotrophin preparation used for ovarian stimulation, and suggests that
      ovarian stimulation with HMG results in an intra-follicular hormone profile more
      similar to that characterizing conception cycles than stimulation with rFSH.
      However, as the present data represent means of FF hormone profiles, they do not
      allow the conclusion of a direct correlation between the intra-follicular
      concentration of a certain hormone and the ability of the corresponding embryo to
      implant and establish an ongoing pregnancy.

PMID- 15151713
TI  - Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist
      administration: randomized controlled trial.
AB  - A significantly lower pregnancy rate following the gonadotrophin-releasing
      hormone (GnRH) antagonist protocol as compared with the long GnRH agonist
      protocol has been reported. The objective of this study was to investigate
      whether increasing the dose of gonadotrophins on the day of antagonist
      administration would increase the pregnancy rate. This study is an open labelled,
      randomized controlled trial and allocation was done using sealed envelopes. One
      hundred and fifty-one subfertile couples undergoing IVF/intracytoplasmic sperm
      injection (ICSI) cycles were included in the study. Ovarian stimulation was
      started on day 3 of the cycle, using 150-300 IU human menopausal gonadotrophin
      (HMG)/day. From day 8 onward, daily vaginal ultrasound and daily urinary LH
      estimation were performed. If a premature LH rise was detected, the cycle was
      cancelled. The antagonist (0.25 mg daily) was started when the leading follicle
      reached 15 mm in mean diameter and LH testing in urine was negative up to and
      including the day of human chorionic gonadotrophin (HCG) injection. Patients were
      randomized on the day of starting the antagonist into two groups: group A, 72
      patients with no increase in HMG dose, and group B, 79 patients in whom the dose
      of HMG was increased by 75 IU on the day of antagonist administration, and
      continued till the day of HCG administration. The results showed no statistically
      significant difference between the groups regarding number of oocytes retrieved,
      embryos obtained, implantation rate, clinical pregnancy rate and multiple
      pregnancy rate. It was concluded that there is no clinical evidence for
      increasing the dose of HMG on the day of antagonist administration.

PMID- 15151714
TI  - Gonadotrophin treatment in patients with polycystic ovary syndrome.
AB  - Gonadotrophin treatment in clomiphene citrate resistant polycystic ovarian
      syndrome (PCOS) patients, using either low-dose step-up or low-dose step-down
      protocols, is highly effective to achieve singleton live births. Concomitant use
      of gonadotrophin releasing hormone analogues (GnRHa), which will block the
      endogenous feedback for monofollicular development during the low-dose step-up
      protocol, should not be employed. It is more difficult to induce ovulation in
      patients with more 'severe' PCOS, characterized by obesity and insulin
      resistance. There is need for optimization of starting doses for both the low
      dose step-up and step-down protocols. Such optimization will prevent
      hyperstimulation due to a starting dose far above the FSH threshold, as well as
      minimize the time-consuming low-dose increments by starting with a higher dose in
      women with augmented FSH threshold. External validation of reported models for
      prediction of FSH response is warranted for tailoring and optimizing treatment
      for everyday clinical practice. Although preliminary, the partial cessation of
      follicular development, along with regression leading to atresia, lends support
      to the LH ceiling theory, emphasizing the delicate balance and need for both FSH
      and LH in normal follicular development. Future well-designed randomized
      controlled trials will reveal whether IVF with or without in-vitro maturation of
      the oocytes will improve safety and efficacy compared with classical ovulation
      induction strategies.

PMID- 15151716
TI  - Medical treatment regimens of hirsutism.
AB  - Hirsutism, which is a common clinical problem in women of reproductive age, is
      characterized by excessive growth of terminal hair in the androgen-sensitive skin
      regions. It is the result of either androgen excess or increased sensitivity of
      the hair follicles to normal levels of androgens. The management, which includes
      cosmetic measures and medical treatment, is far from satisfactory. Anti-androgen
      drugs play a key role in the treatment of hirsutism, but they have some side
      effects which may result in cessation of the drug. On the other hand, anti
      androgen treatment often needs to be continued for a long time. So, safe,
      inexpensive, and effective anti-androgen drugs are needed. Recently low-dose anti
      androgen drugs have been shown to be effective in the maintenance of treatment.
      On the other hand, cyproterone acetate plus ethyniloestradiol and spironolactone,
      cyproterone acetate plus ethyniloestradiol and finasteride, and spironolactone
      and finasteride combinations have been used successfully in decreasing the
      hirsutism score. There are also some promising data regarding the effects of
      insulin sensitizers in the treatment of hirsutism, particularly in patients with
      polycystic ovarian syndrome. In the present review, the main features of anti
      androgen drugs, new combined treatments, and insulin sensitizers in the treatment
      of hirsutism are discussed.

PMID- 15151718
TI  - In-vitro maturation of immature oocytes for infertile women with PCOS.
AB  - Immature oocyte retrieval followed by in-vitro maturation (IVM) is a promising
      potential treatment option, especially for women who are infertile through
      polycystic ovarian syndrome (PCOS). Although the pregnancy and implantation rates
      of IVM treatment are not as high as conventional IVF treatment, IVM treatment has
      many advantages for infertile women with PCOS, because this group of patients is
      extremely sensitive to stimulation with exogenous gonadotrophins and is at
      increased risk of developing ovarian hyperstimulation syndrome (OHSS). Different
      protocols have been used before immature oocyte retrieval, indicating that there
      are beneficial effects with FSH or LH priming on oocyte maturation. To date, the
      clinical pregnancy and implantation rates obtained from IVM treatment in
      infertile women with PCOS are approximately 30-35% and 10-15% respectively.
      Therefore, as an option, IVM treatment can be offered to women with PCOS instead
      of conventional IVF treatment with ovarian stimulation.

PMID- 15151719
TI  - In-vitro maturation of germinal-vesicle oocytes and cryopreservation in metaphase
      I/II: a possible additional option to preserve fertility during ovarian tissue
      cryopreservation.
AB  - This study describes the possibility of combining two options in order to
      preserve female fertility: cryopreservation of human ovarian tissue and in-vitro
      matured germinal vesicle (GV) oocytes retrieved during tissue dissection. In
      contrast to ovarian tissue cryopreservation, the cryostorage of in-vitro matured
      unfertilized metaphaseI/II oocytes could be a more realistic option. This concept
      of preserving fertility before chemotherapy and/or radiotherapy without a long
      time delay could be an additional reason for favouring ovarian tissue
      cryopreservation. This concept is discussed in regard to two cases.

PMID- 15151720
TI  - Vitrification versus programmable rate freezing of late stage murine embryos: a
      randomized comparison prior to application in clinical IVF.
AB  - A prospective randomized trial was performed to compare post-thaw development of
      murine blastocysts following programmable rate freezing and two methods of
      vitrification. Frozen 2-cell murine embryos (n = 429) thawed and cultured for 48
      h, were randomly allocated by stage of development into four groups: control (not
      refrozen), programmable rate freezing (PR) in 0.25 ml straws, vitrification in
      flexible micropipettes by immersion in super-cooled (VSC) liquid nitrogen (LN2),
      and vitrification in flexible micropipettes by immersion in LN2 (VLN). Survival,
      developmental stage progression, presence or absence of an inner cell mass (ICM),
      and cell counts were recorded 24 h post-thaw. All measured outcomes were
      different between embryos from the control group and all freezing methods.
      Controlled-rate freezing resulted in the lowest total cell counts and fewest
      embryos with a distinct ICM. A higher percentage of embryos survived 24 h post
      thaw, progressed to more advanced developmental stages and had higher total cell
      counts after VLN compared with PR. Moreover, fewer embryos, frozen by either PR
      or VSC, contained a detectable ICM compared with VLN. These data demonstrate that
      vitrification may be a better method for freezing murine blastocysts than PR, and
      may prove to be a superior method for freezing human blastocysts.

PMID- 15151722
TI  - Inhibition of oocyte fertilization by assisted reproductive techniques and
      increased sperm DNA fragmentation in the presence of Candida albicans: a case
      report.
AB  - The effects of Candida albicans on sperm parameters and the outcome of
      infertility treatment are unclear. This report describes a lack of fertilization
      after assisted reproductive techniques and increased sperm DNA fragmentation in
      an infertile patient with male accessory gland infection due to Candida albicans.
      He had normal sperm parameters and, therefore, underwent conventional IVF for a
      female factor of infertility. No spermatozoa or only one spermatozoon per oocyte
      were found attached to the zona pellucida of the six mature oocytes retrieved. A
      new semen sample was then requested from the patient to perform intracytoplasmic
      sperm injection (ICSI) on the same oocytes, but again no fertilization resulted.
      Candida albicans was detected in the medium where spermatozoa were co-incubated
      with oocytes and subsequently in the urethral swabs. It did not have any
      detrimental effect on sperm parameters soon after ejaculation or following
      separation of motile spermatozoa by swim-up technique. Fertilization failure
      after assisted reproduction treatment was associated with an increased percentage
      of motile spermatozoa having chromatin packaging abnormalities, externalization
      of phosphatidylserine and DNA fragmentation. In conclusion, Candida albicans did
      not affect sperm parameters, but increased sperm chromatin packaging damage and
      apoptosis that might have caused fertilization failure after assisted
      reproduction treatment in this couple.

PMID- 15151724
TI  - Support for Barker hypothesis upheld in rat model of maternal undernutrition
      during the preimplantation period: application of integrated 'random effects'
      statistical model.
AB  - In response to a recent paper published in Reproductive BioMedicine Online by
      Walters and Edwards (2003), this study reports the application of a random
      effects regression analysis for evaluation of integrated data involving maternal
      and embryo/offspring components. Using this method, it is possible to confirm the
      conclusions of an earlier study that rat maternal undernutrition during the
      preimplantation period results in blastocyst cell number reduction and post-natal
      outcomes, including altered growth rates and elevated blood pressure.

PMID- 15151726
TI  - Candidate lineage marker genes in human preimplantation embryos.
AB  - Cell allocation and subsequent lineage commitment in the human embryo may be
      established as early as in the unfertilized oocyte. This phenomenon might be the
      result of subtle differences of gene expression and protein distribution. To
      assess whether gene expression profiling by reverse transcription-polymerase
      chain reaction could be a suitable tool for the detection of cell allocation and
      lineage commitment, the expression pattern of the putative inner cell mass marker
      gene Oct-4 and the trophectodermal marker genes beta-HCG and beta-LH were
      correlated in individual blastomeres of preimplantation human embryos. In 2- to 5
      cell stage embryos, expression of beta-HCG and Oct-4 mRNA was negatively
      correlated in all blastomeres with statistical significance, suggesting that cell
      allocation can be assessed by those markers at early stages. In 7- to 10-cell
      stage embryos, expression of beta-LH and Oct-4 mRNA was negatively correlated in
      some blastomeres without statistical significance, suggesting that more
      experiments are necessary to decide if lineage commitment can be assessed in some
      cells by those markers at later stages.

PMID- 15151728
TI  - A strategy for treatment of couples with unexplained infertility who failed to
      conceive after intrauterine insemination.
AB  - Couples with unexplained infertility treated unsuccessfully with intrauterine
      insemination often receive further treatment with IVF or intracytoplasmic sperm
      injection (ICSI). The aim of this study was to evaluate the frequency of
      fertilization and fertilization failure with respect to the method of
      fertilization used, when half of the sibling oocytes were fertilized by
      conventional IVF and insemination and the remainder by ICSI. Included was the
      first IVF/ICSI treatment of 248 unexplained infertile couples who had failed to
      conceive after three IUI cycles. An overall pregnancy rate per embryo transfer of
      57% was observed. A significantly better fertilization rate was obtained after
      ICSI as compared with IVF (68 versus 46%) (P < 0.005), and total fertilization
      failure following ICSI and IVF treatment was seen in 4.4 and 25% of the cycles
      respectively. The group who experienced total fertilization failure after IVF had
      normal semen parameters, although significantly lower sperm concentration and
      motility as compared with the entire study group. Transfer of their ICSI
      fertilized oocytes subsequently resulted in a pregnancy rate of 49.2% per
      transfer. The policy of splitting the sibling oocytes can effectively minimize
      complete fertilization failure while maintaining high chances of achieving a
      pregnancy. At the same time, the optimal fertilization method for subsequent
      treatment cycles can be determined.

PMID- 15151729
TI  - Effect of treatment of intrauterine pathologies with office hysteroscopy in
      patients with recurrent IVF failure.
AB  - The study was conducted to evaluate if the diagnosis and treatment of
      intrauterine lesions with office hysteroscopy is of value in improving the
      pregnancy outcome in patients with recurrent in-vitro fertilization and embryo
      transfer failure. Four hundred and twenty-one patients who had undergone two or
      more failed IVF-embryo transfer cycles were prospectively randomized into two
      groups. Group I (n = 211) did not have office hysteroscopic evaluation, Group II
      (n = 210) had office hysteroscopy. The patients who had normal hysteroscopic
      findings were included in Group IIa (n = 154) and patients who had abnormal
      hysteroscopic findings were included in Group IIb (n = 56). Intrauterine lesions
      diagnosed were operated during the office procedure. Fifty-six (26%) patients in
      Group II had intrauterine pathologies and the treatment was performed at the same
      time. No difference existed in the mean number of oocyte retrieved, fertilization
      rate, number of embryos transferred or first trimester abortion rates among the
      patients in groups. Clinical pregnancy rates in Group I, Group IIa and Group IIb
      were 21.6%, 32.5% and 30.4% respectively. There was a significant difference in
      the clinical pregnancy rates between patients in Group I and Group IIa (21.6% and
      32.5%, P = 0.044, respectively) and Group I and Group IIb (21.6% and 30.4%, P =
      0.044, respectively). There was no significant difference in the clinical
      pregnancy rate of patients in Groups IIa and IIb. Patients with normal
      hysterosalpingography but recurrent IVF-embryo transfer failure should be
      evaluated prior to commencing IVF-embryo transfer cycle to improve the clinical
      pregnancy rate.

PMID- 15151730
TI  - Prediction of pituitary down-regulation by evaluation of endometrial thickness in
      an IVF programme.
AB  - The aim of this retrospective study was to determine whether pituitary down
      regulation after gonadotrophin-releasing hormone analogue (GnRHa) administration
      can be accurately predicted by transvaginal ultrasonographic measurement of
      endometrial thickness in the presence of menstruation. All cycles of an
      IVF/intracytoplasmic sperm injection programme in which a long protocol of GnRHa
      was used for ovarian stimulation were analysed. Overall, 209 patients underwent
      223 treatment cycles. Using a serum oestradiol concentration of 50 pg/ml as a cut
      off point, the sensitivity, specificity, predictive value and false positive and
      false negative values were calculated for prediction of pituitary down-regulation
      from endometrial thickness measurements. Pituitary down-regulation was achieved
      in 223 treatment cycles in 180 patients (80%). The best combination of the
      highest specificity (71.7%) and sensitivity (62.5%) is achieved with a linear
      appearance of the endometrium. Therefore, ultrasonographic measurement of
      endometrial thickness should be used in combination with serum oestradiol
      concentration in estimating pituitary down-regulation after GnRHa. In conclusion,
      the linear appearance of endometrium can be as reliable as serum oestradiol
      concentration in prediction of pituitary down-regulation after GnRHa.

PMID- 15151731
TI  - Cumulative pregnancy rates and drop-out rates in a German IVF programme: 4102
      cycles in 2130 patients.
AB  - Cumulative pregnancy rates are useful in counselling couples on their chance of
      conceiving during infertility treatment. Patients also have to be counselled
      about the physical and psychological stress of infertility treatment. Beside the
      pregnancy rates, drop-out rates are a direct, and may be the most important,
      marker of physician quality in an IVF programme. Data from 4102 IVF cycles in
      2130 patients in Germany were analysed retrospectively. Data were analysed using
      descriptive statistics as well as the Kaplan-Meier procedure. A real cumulative
      pregnancy rate of 31.2% was achieved after four cycles with an expected
      cumulative pregnancy rate (ECPR) of 53.3%. Age was a significant factor regarding
      pregnancy rates (ECPR after four cycles: 57.1% <35 years, 44.8% > or =35 years,
      35.4% > or =40 years). The drop-out rate of non-pregnant patients increased from
      39.9% after the first cycle to 62.2% after the fourth cycle, indicating the
      enormous stress and frustration that increased during the course of treatment.
      The drop-out rate should be used as an important marker of quality control. The
      presented data give, for the first time, a good basis for this counselling
      procedure in Germany.

PMID- 15151732
TI  - The weight of chronic pelvic pain.

PMID- 15151733
TI  - Analysis of molecular aberrations in ovarian cancer allows novel target
      identification.
AB  - The completion of the Human Genome Project and recent advances in functional
      genomic, proteomic, and high-throughput screening methodologies have provided
      powerful tools for determining the mechanisms of human diseases, including
      complex polygenic diseases such as ovarian cancer. These developments may
      eventually lead to individualized molecular medicine, which is the treatment of
      patients based on the underlying genetic defects in their tumours and their own
      genetic makeup. A plethora of novel therapeutic agents that act on specific
      molecular targets defined by cancer genetics are under development. There is thus
      a great deal of interest in determining how specific genes and proteins function
      in cancers, in order to further the understanding of cancer initiation and
      progression; to aid in identifying biomarkers, therapeutic targets, and
      determinants of drug responsiveness; and to progress the development of novel
      antitumour agents.

PMID- 15151734
TI  - Risk of fetal exposure to folic acid antagonists.
AB  - BACKGROUND: Several folic acid antagonists are considered by the Food and Drug
      Administration (FDA) to be toxic or potentially toxic to fetuses, including some
      folic acid antagonists that were once considered safe, such as trimethoprim.
      Information on fetal exposure to folic acid antagonists is sparse. METHODS: In
      this study, we conducted a thorough search of English literature on human uses of
      various folic acid antagonists, and made an indirect estimation of potential
      exposure to folic acid antagonists during pregnancy by analyzing the data from
      the outpatient prescription drug database of the Canadian province of
      Saskatchewan. RESULTS: The numbers of women of reproductive age (16 to 44 years)
      with at least 1 prescription of dihydrofolate reductase inhibitors was 14195 in
      1977, 20455 in 1991, and 16054 in 1999. Corresponding figures for other folic
      acid antagonists were 2136, 1954, and 2720, respectively. According to these
      figures, the rates of prescription given to women of reproductive age in any
      particular calendar year were 8.45% (95% confidence interval [CI], 8.33% - 8.57%)
      for dihydrofolate reductase inhibitors and 1.14% (95% CI, 0.67% - 1.61%) for
      other folic acid antagonists. CONCLUSIONS: Prescription of folic acid antagonists
      to women of reproductive age is quite frequent, and there has been no apparent
      decline in prescriptions in recent years. Increase in unplanned pregnancies in
      industrial countries, lack of adequate scientific evidence on the adverse effects
      of folic acid antagonists, potential ignorance in clinical practice, and
      conflicting needs to treat maternal diseases and to protect fetuses, can all lead
      to frequent prescription of potentially toxic folic acid antagonists to pregnant
      women, thus posing serious threat to the fetuses. In this paper, strategies that
      may be used to reduce the risk of fetal exposure to folic acid antagonists are
      proposed.

PMID- 15151736
TI  - Canadian access to hormonal contraceptive drug choices.
AB  - On October 29, 2002, Health Canada issued Guidance for Industry: Clinical
      Development of Steroidal Contraceptives Used by Women. The original draft of this
      guideline, published July 4, 2001, included recommendations for clinical trials
      in excess of those required in Europe and the United States. The proposed
      requirements, which reflected Health Canada's views, had the potential to
      discourage contraceptive research in Canada and to block registration of new
      products. To evaluate the impact of Canada's hormonal contraceptive regulation, a
      comparative analysis of the availability of products in various countries was
      performed, along with an evaluation of the time required from submission to
      approval of a new drug. Women in Canada have access to 35% of the contraceptive
      products available worldwide and to 37% of the hormonal contraceptives available
      worldwide, compared with 58% and 59% respectively, in the United States; 52% and
      54% respectively, in the United Kingdom; 44% and 54%, respectively, in France;
      and 44% and 50% respectively, in Sweden. Regarding the more recent contraceptive
      products available worldwide, women in Denmark have the most choices (67% of
      available products), whereas women in Canada have the least (only 22% of
      available products). Eleven of 12 oral contraceptive products recently approved
      in other countries have either not been submitted for approval in Canada or
      remain in the Canadian regulatory process. Although the time-to-approval period
      in Canada, for drugs in general, is 6 months longer than in the United States,
      the mean lag time for 6 contraceptive products is 29.6 months as of January 1,
      2004, and no oral contraceptives have been approved in Canada since 1997.

PMID- 15151737
TI  - Complete adult vulvar fusion: a case report.
AB  - BACKGROUND: Labial fusion is most commonly seen in prepubertal girls and in
      postmenopausal women affected by advanced lichen sclerosus et atrophicus.
      Postpartum labial fusion is a rare phenomenon for a woman with no evidence of
      hypoestrogenism. CASE: A woman with a normal delivery and a normal postpartum
      examination presented 7 years later with a complete vulvar closure from the
      urethral opening to the posterior fourchette. CONCLUSION: Complete vulvar fusion
      can rarely occur without any evidence of hypoestrogenism. It is managed by
      surgical incision and perineorrhaphic correction without sequelae.

PMID- 15151735
TI  - Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage
      following vaginal delivery:a double-blind randomized trial.
AB  - OBJECTIVES: To compare the efficacy of a single 100 micro g intramuscular (IM)
      carbetocin injection, a long-acting oxytocin agonist, to a 2-hour 10 IU oxytocin
      intravenous (IV) infusion, in reducing the incidence and severity of postpartum
      hemorrhage (PPH) in women at risk for this condition. METHODS: A randomized,
      double-blind, placebo-controlled study was conducted at 2 hospital centres,
      including 160 women with at least 1 risk factor for PPH. Eighty-three women
      received 100 microg carbetocin IM and an IV placebo immediately after placental
      delivery, while 77 women received placebo IM and oxytocin IV infusion. Complete
      blood count was collected at entry and 24 hours postpartum. All outcome measures,
      including the need for additional uterotonic agents or uterine massage, blood
      loss, and drop in hemoglobin and hematocrit, were analyzed using chi-square,
      Fisher exact, and Student t tests. RESULTS: Population profile and risk factors
      for PPH were similar for each group. No significant difference was observed in
      the number of women requiring additional uterotonic medication (12 in each
      group). However, in the carbetocin group, 36 of the 83 women (43.4%) required at
      least 1 uterine massage compared to 48 of the 77 women (62.3%) in the oxytocin
      group (P <.02). Overall, uterotonic intervention was clinically indicated in 37
      of the women (44.6%) receiving carbetocin compared to 49 of the women (63.6%)
      given an IV oxytocin infusion (P <.02). There were no differences in laboratory
      PPH indicators between the 2 groups.

PMID- 15151738
TI  - The detection and management of vaginal atrophy.
AB  - OBJECTIVE: To support the practitioner in the diagnosis of vaginal atrophy and in
      the management of the related symptoms. OPTIONS: The modalities of evaluation
      range from basic pelvic examination, examination of the vulva, and laboratory
      tests. OUTCOMES: A comprehensive approach to the detection of vaginal atrophy and
      a discussion of available therapeutic and nontherapeutic options. 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: Diagnosis of vaginal atrophy is often a challenge
      because women are unwilling to report symptoms, which have the potential to
      significantly decrease their quality of life. Increased clinical suspicion is the
      first step in the diagnosis of vaginal atrophy, which will prompt the initiation
      of safe therapies with proven efficacy. RECOMMENDATIONS: 1. Health-care providers
      should routinely assess postmenopausal women for the symptoms and signs of
      vaginal atrophy, a common condition that exerts significant negative effects on
      quality of life. (III-C) 2. Regular sexual activity should be encouraged to
      maintain vaginal health. (II-2B)3. Women experiencing recurrent urinary tract
      infections should be instructed that consumption of pure cranberry-lingonberry
      juice, rather than cranberry drink, will decrease their risk of urinary tract
      infections. (I-A) 4. Vaginal moisturizers applied on a regular basis have an
      efficacy equivalent to local hormone replacement for the treatment of local
      urogenital symptoms such as vaginal itching, irritation, and dyspareunia, and
      should be offered to women wishing to avoid use of hormone replacement therapy.
      (I-A) 5. Women experiencing vaginal atrophy can be offered any of the following
      effective vaginal estrogen replacement therapies: conjugated equine estrogen
      cream (I-A), a sustained-release intravaginal estradiol ring (I-A), or a low-dose
      estradiol tablet (I-A). 6. Although systemic absorption of estrogen can occur
      with local preparations, there is insufficient data to recommend annual
      endometrial surveillance in asymptomatic women using local estrogens. (III-C) 7.
      For menopausal women experiencing recurrent urinary tract infections and who have
      no contraindication to local hormone replacement, vaginal estrogen therapy should
      be offered. (I-A).

PMID- 15151740
TI  - [Application of vital dye CFDA-SE to study lymphocytic proliferation].
AB  - AIM: To explore the application value of vital dye CFDA-SE to study of
      lymphocytic proliferation. METHODS: CFDA-SE staining, fluorescence antibody
      labeling, flow cytometry and related software were used to detect the
      fluorescence intensity and analysis the proliferation kinetics of lymphocytes and
      their subsets after stimulation with polyclonal stimulators. RESULTS: Lymphocytes
      divided after stimulation of PDB+ionomycin or ConA for 48 h, manifesting the
      serial halving of fluorescence intensity. CsA inhibited the proliferative effect
      of ConA on lymphocytes and no CFSE fluorescence halving were seen. Proliferation
      of CD4(+) T cells and CD8(+) T cells were asynchronous after ConA stimulation for
      48 h, which became more obvious at the time of 72 h. Proliferation-related indexs
      got ten from ModFit(TM) software showed that the proliferative effect of ConA on
      CD8(+) T cells was stronger than that on CD4(+) T cells. CONCLUSION: CFDA-SE
      staining combined with fluorescent antibody labeling and cytometry were powerful
      tools for analysis of lymphocytic proliferation.

PMID- 15151739
TI  - Comparison of IL-6-induced STAT1 activation in different responsive cells.
AB  - AIM: To investigate the activation status of signal transducer and activator of
      transcription 1 (STAT1) induced by interlerkin-6 (IL-6) in different responsive
      cells. METHODS: Immunoblot analysis was performed with antibodies against STAT1
      and tyrosine-phosphorylated STAT1. RESULTS: It's found that IL-6 had growth
      promoting effects on 7TD1 and TF1 cells but had little effect on the tyrosine
      phosphorylation of STAT1. On the other hand, IL-6 activated STAT1 in a dose and
      time-dependent manner in M1, R2 and U937 cells which underwent growth arrest and
      macrophage differentiation upon IL-6 induction. CONCLUSION: These results suggest
      that IL-6-induced STAT1 activation might be associated with growth-inhibitory
      effects, and our data might help to explain why IL-6 exerts distinct biological
      effects in different target cells.

PMID- 15151741
TI  - [Study on immunoregulatory functions of E.coli heat-labil enterotoxin B subunit].
AB  - AIM: To explore the immunoregulatory functions of Escherichia coli heat-labil
      enterotoxin B subunit(LTB) and its possible mechanism. METHODS: The rLTB in
      engineering bacteria VSP60 was purified by Sephacryl S-100 gel filtration
      chromatography. BALB/c mice were immunized nasally with hen egg lysozyme(HEL)
      alone or in combination with various doses of LTB. After three times of
      immunization, specific anti-HEL IgG and IgA levels in serum and small intestinal
      secretory fluid were determined by ELISA. The effects of LTB on alloantigen- and
      ConA- mediated lymphocyte proliferation reactions were measured by (3)H-TdR
      incorporation assay. RESULTS: Very weak serum anti-HEL IgG response and no IgA
      response were detected in mice immunized with HEL alone. However, levels of both
      serum anti-HEL IgG, IgA and intestinal secretory fluid IgA in mice immunized with
      various doses of HEL+LTB were higher than those in mice immunized with HEL
      alone(P<0.001). In-vitro, LTB could obviously inhibit the lymphocyte
      proliferation induced by mitogen and alloantigen. CONCLUSIONS: The effects of LTB
      protein on immnune system may be bi-directional. LTB is not only a powerful
      mucocal immunoadjuvant in-vivo, but also a potent immunosuppressive agent In
      vitro.

PMID- 15151742
TI  - [Expression and regulation of a novel soluble adhesive molecule sCD226 on human
      endothelial cells].
AB  - AIM: To explore the expression and regulation of a novel soluble adhesive
      molecule sCD226 on HUVECs. METHODS: The contents of sCD226 and NO in culture
      supernatant of LPS activated human umbilical vein endothelial cells (HUVECs) were
      detected by ELISA and Greiss method respectively, and linear correlativity of
      contents between sCD226 and NO was analysed. The influence of anti-TNF-alpha mAb
      and iNOS inhibitor on LPS-induced sCD226 production was observed by ELISA.
      RESULTS: (1)LPS might markedly stimulate sCD226 production from HUVECs in a dose-
      and time-dependent manner. The amount of sCD226 came to 188.5 microg/L when
      endothelial cells were stimulated by 100 mg/L LPS for 3 days. (2)The production
      of NO and sCD226 showed linear correlation when HUVECs were stimulated by 100
      mg/L LPS.(3)LPS-induced sCD226 production in HUVECs was inhibited significantly
      by anti-TNF-alpha mAb and iNOS inhibitor. CONCLUSION: LPS-activated-HUVECs can
      secret sCD226 and the generation of sCD226 is closely correlated with the
      production of NO and TNF-alpha.

PMID- 15151743
TI  - [Cloning, prokaryotic expression of LAIR and identification of their
      immunological reactivities].
AB  - AIM: To clone and express the leukocyte-associated immunoglobulin-like receptor
      (LAIR) and to identify the immune reactivity of LAIR-2 to anti-LAIR-1 specific
      monoclonal antibodies(mAb). METHODS: Genes encoding LAIR-1 and LAIR-2 were cloned
      by RT-PCR from human peripheral blood mononuclear cells(PBMC) and two leukemia
      cell lines Jurkat and HL-60. The extracellular region gene of LAIR1 and LAIR-2
      were inserted into vector pGEX-4T-3 expressing GST fusion protein, expressed on
      IPTG induction and purified through glutathione-sepharose 4B column. The
      immunological reactivity of expressed LAIR-2 to anti-LAIR-1 mAb was identified by
      indirect ELISA. RESULTS: LAIR-1 and LAIR-2 cDNAs had been cloned and expressed.
      Five new LAIR-1 cDNA isoforms were cloned. Among them, two isoforms from HL-60
      included LAIR-1 open reading frames (ORF) and three isoforms from Jurkat were
      LAIR-1 cDNA segments. The LAIR-1 and LAIR-2 showed different immunological
      reactivities. CONCLUSION: The transcription, processing after transcription and
      expression of LAIRs may be related to disparities in individuals and disease
      status. The difference in immunological reactivity may be involved in their
      structure.

PMID- 15151744
TI  - [Characterization of Mycobacterium tuberculosis polypeptide antigen capable of
      stimulating the proliferation of human gammadeltaT cells].
AB  - AIM: To analyse biological properties of Mycobacterium tuberculosis polypeptide
      antigen(Mtb-Ag) that could stimulate the proliferation of human gammadeltaT
      cells. METHODS: Mtb secretory proteins and Mtb-Ag treated via dialysis or with
      pronase were used to stimulate human PBMCs. After being cultured for 10 days, the
      phenotype of responsive cells was analysed by flow cytometry. RESULTS: The
      proliferation stimulating activity to human gammadeltaT cells of dialysed Mtb-Ag
      did not decrease remarkably, whereas that of the pronase-treated Mtb-Ag reduced
      significantly. Moreover, the proliferative stimulating activity to gammadeltaT
      cells of Mtb-Ag was notably higher than Mtb secretory protein. CONCLUSION: The
      component in Mtb-Ag that can stimulate the proliferation of human gammadeltaT
      cells is a non-secretory and protase-sensitive polypeptides with M(r) over 10
      000.

PMID- 15151745
TI  - [Construction of the eukaryotic expression vector of mouse beta-NGF and its
      expression in NIH 3T3 fibroblast cell lines].
AB  - AIM: To construct the eukaryotic expression vector of mouse nerve growth factor
      gene and express it in NIH 3T3 fibroblast cell lines. METHODS: By gene
      recombination technique, mouse beta-NGF cDNA was inserted into mammlian
      expression vector pcDNA3.1+. The recombinant plasmid was verified with
      restriction enzyme digestion analysis. NIH 3T3 cell grown to log phase was
      transfected with this vector using FuGENE(TM) 6 transfection reagent. The
      transfected cells were grown in DMEM medium containing G418 at 72 hours after
      transfection, and the positive clones were selected in G418 medium until the 20
      th day. The expression of NGF and its biological activity were analyzed by
      Western blot and the neurite outgrowth of PC12 cells stimulated by culture
      supernatant of positive clones respectively. RESULTS: The beta-NGF gene was
      expressed successfully in NIH 3T3 cells. The culture supernatant could stimulate
      the neurite outgrowth of PC12 cells. CONCLUSION: The eukaryocyte expression
      vector was constructed successfully. The NGF gene was expressed successfully in
      the transfected NIH 3T3 cells with good biological activity, which laid the
      foundation for gene therapy of nervous system diseases.

PMID- 15151746
TI  - [Study on the affinities of antagonistic peptides with HAb18G/CD147 on the
      hepatocellular carcinoma cells].
AB  - AIM: To study the affinities of antagonistic peptides with HAb18G/CD147 on the
      hepatocellular carcinoma cells. METHODS: Fluorescence-activated cell sorting
      analysis(FACS) was used to detect the expression of HAb18G antigen on HHCC and
      SMMC7721 cells. Antagonistic peptides(APs) AP-1, AP-2 and AP-6 were labelled with
      biotin at their N-terminals. The binding abilities of APs to HHCC or SMMC7721
      cells were determined by FACS and confocal microscope. RESULTS: HAb18G antigen
      was highly expressed on the HHCC and SMMC7721 cells. AP-6 has the highest
      affinity for HHCC and SMMC7721 cells compared with AP-1 and AP-2. CONCLUSION:
      Antagonistic peptides of HAb18G/CD147 have high affinities with HAb18G/CD147 on
      the hepatocellular carcinoma cells.

PMID- 15151747
TI  - [Expression of Japanese encephalitis virus E protein in methylotrophic yeast
      Pichia pastoris].
AB  - AIM: To express Japanese encephalitis virus (JEV) E protein in methylotrophic
      yeast Pichia pastoris. METHODS: The gene coding for JEV E protein was sub-cloned
      into vector pPIC9k. The constructed plasmid was transformed into yeast SMD1168 by
      electroporation. The recombinant transformants with a high copy number of the
      plasmid were selected by using MD plate and G418. The expression of E protein in
      yeast was induced by the addition of methanol and analyzed by SDS-PAGE and
      Western blot. RESULTS: The protein was produced at a yield of 50 mg per litre of
      culture. Owing to heterogeneous glycosylation, relative molecular mass (M(r)) of
      the expressed E protein was sized about 113 000 and 78 000. CONCLUSION: JEV E
      protein was expressed successfully in yeast Pichia pastoris, which should be
      useful for the production of diagnostic reagents and genetically engineered
      vaccine of JEV.

PMID- 15151748
TI  - [Construction and identification of the E.coli-BCG shuttle vector expressing
      lipoprotein Der p2 on cell wall of mycobacterium vaccae].
AB  - AIM: To construct the E.coli-BCG shuttle vector carrying and expressing dust mite
      antigen gene Der p2 on cell wall of mycobacterium vaccae. METHODS: The gene
      fragment encoding 19 kDa antigen and the upstream control element (19-ss) was
      amplified by PCR from the mycobacteria tuberculosis H37Rv.Subsequently, the 19-ss
      gene was cloned into the E.coli-BCG shuttle vector pOLYG, which can schlepped and
      expressed exogenous antigen gene on cell wall of mycobacteria and containing the
      Der p2 gene. The expression of Der p2 gene in mycobacterium vaccae determined by
      indirect immunofluorescence staining. RESULTS: Sequencing proved that the cloned
      sequence of 19-ss gene was correct. The constructed E.coli-BCG shuttle vector
      (pCW) containing 19-ss gene had function of shuttle between E.coli and
      mycobacteria, and mediated the expression of antibiotic resistance gene. Indirect
      immunofluorescence staining indicated that the Der p2 gene was expressed in the
      form of lipoprotein on surface of the mycobacterium vaccae. CONCLUSION: E.coli
      BCG shuttle vector has been constructed successfully, which can express exogenous
      antigen gene as a chimeric protein on cell wall.

PMID- 15151750
TI  - [Gene cloning and prokaryotic expression of the PID domain of human DOC-2
      molecule].
AB  - AIM: To clone the PID domain of human DOC-2 (nDOC-2) and express it in E.coli
      DH5alpha. METHODS: The cDNA fragment encoding the PID domain of nDOC-2 was
      amplified by RT-PCR from normal human ovarian tissue and cloned to pUC19. The DNA
      fragment from the pUC19-nDOC-2 digested with BamH I and EcoR I was ligated to the
      BamH I/EcoR I digested prokaryotic expression vector pGEX-4T-1.The expression of
      fusion protein was induced with IPTG and the expressed product was identified by
      SDS-PAGE. RESULTS: (1)The sequencing and endonucleases digestion analysis showed
      that the fragment of nDOC-2 gene was insert into vectors pUC19 and pGEX-4T
      1;(2)SDS-PAGE showed the nDOC-2 gene had been expressed in E.coli DH5alpha.
      CONCLUSION: The PID domain of nDOC-2 was expressed successfully in prokaryote,
      which makes preparation for further researching the function of DOC-2 and
      preparing antibodies to DOC-2 protein.

PMID- 15151749
TI  - [The effects of Zheng's plant-protein on the proliferation of lymphocytes from
      patients with breast cancer and precancer].
AB  - AIM: To study the effect of Zheng's plant-protein(ZPP) and
      phytohemagglutinin(PHA) on proliferation of peripheral blood lymphocytes (PBL)
      and it's application value on the early diagnosis and therapy of breast cancer.
      METHODS: The proliferation assay was used (3)H-TdR incorporation test. The
      phenotypes of PBL were analysised by flow cytometry(FCM). RESULTS: The ZPP
      significantly and selectively enhanced proliferation activity of PBL of primary
      breast and precancer cases. Their stimulation indexes(SI) were 3.00+/-1.45 and
      2.53+/-0.80, while the SI of simple hyperplasia cases and normal subjecties were
      1.18+/-0.47 and 1.06+/-0.91. The former were significantly higher than the latter
      (P<0.01). The ZPP was also enhanced the expression level of CD3(+),CD4(+) and
      CD8(+) of PBL. CONCLUSION: This results suggest that ZPP might be a beast cancer
      common antigen. These activity might be used in clinical implication to diagnosis
      and treatment of breast cancer.

PMID- 15151751
TI  - [Study on corelation between InsP(3) generation and TCR/ CD3 complex-mediated
      [Ca(2+)]i responses in T cells from SLE patients].
AB  - AIM: To demonstrate whether function disorder of T cells from SLE patients was
      relative to abnormal biochemical pathways mediated by TCR/ CD3 complex and
      whether this abnormality was relative to the InsP(3) production. METHODS: Human T
      cells were isolated through Nylon-columns from heparinized peripheral blood from
      SLE patients and control individuals. Percentage of CD3(+) T cells was detected
      by flow cytometry. After cross-linking of anti-CD3 mAbs to sheep anti-mouse IgG
      and stimulating T cells, the changes of free calcium ion within T cells was
      observed successively for 10 minutes by an adhesion cytometry. Flow cytometry was
      used to detect the difference in positive rate between normal individual's and
      SLE patient's T cells. Level of InsP(3) was detected by a radioreceptor assay
      kit. RESULTS: (1)Flow cytometry analysis showed that CD3(+) T cells obtained
      through nylon column accounted for more than 90%.(2)The base line recordings of
      [Ca(2+)]i response from SLE patients were similar to that from normal control
      (P=0.105). Peak and plateau [Ca(2+)]i response in T cells of SLE patients were
      significantly higher than that in the control group (P<0.001). (3)The percentage
      of the CD3(+) T cells was similar in both individuals (P=0.665).(4)No differences
      in the anti-CD3 mAb-mediated InsP(3) generation were found between the two groups
      (P=0.537). CONCLUSION: TCR/ CD3-mediated [Ca(2+)]i responses in T cells from SLE
      patients is abnormal, and the abnormality has no relation to InsP(3) generation.

PMID- 15151752
TI  - [The biological characteristics of beta glucuronidase cDNA transfected renal
      cancer cell line GRC 1/betaG].
AB  - AIM: To establish a renal carcinoma cell line which can highly express beta
      glucuronidase(betaG), and to observe the biological characteristics of the
      transfected cells. METHODS: Recombinant eukaryotic expression vector pcDNA3.1
      betaG was constructed. It was transfected into renal cancer cells GRC-1 via
      liposome. The transcription and expression of betaG gene were detected by dot
      blot and Western blot. The biological characteristics of the betaG gene
      transfected cells was observed under light microscope, transmission electron
      microscope and flow cytometry. RESULTS: Dot blot and Western blot detection
      confirmed that the betaG gene had been stably integrated into the genomic DNA of
      the GRC-1 cells and was highly expressed. Transmission electron microscope
      observation showed that the lysosomes and endoplasmic reticulum were abundant,
      the number of microvili and process was significantly increased in the
      transfected cells, but growth condition and cell cycle of GRC-1 cells had no
      notable difference before and after transfection. CONCLUSION: A renal carcinoma
      cell line that can highly express betaG gene was established, which lays the
      foundation for further study on gene therapy.

PMID- 15151753
TI  - [Cloning of human testicular carcinoma antigen MAGE-E1 gene and its expression in
      E.coli].
AB  - AIM: To clone and express the testicular carcinoma antigen MAGE-E1 gene in
      E.coli. METHODS: The cDNA encoding human MAGE-E1 gene was amplified by RT-PCR
      from human glioma cell line BT-325, then the MAGE-E1 gene was inserted into
      plasmid pGEM-T easy. After sequencing, the MAGE-E1 was cloned into the
      prokaryotic expression vector pGEX-4T-2 to construct the recombinant expression
      vector pGEX-4T-2-MAGE-E1 which was used to transform E.coli. RESULTS: The
      expressed product reached the highest level at 5 h after IPTG induction. SDS-PAGE
      and scanning analysis of gel density indicated that the expressed protein was
      about M(r) 41 000 and account for 35% of the total bacterial protein. CONCLUSION:
      The high efficient expression of the MAGE-E1 gene fragment lays the foundation
      for further preparing antibody against MAGE-E1 protein and the tumor vaccine for
      glioma immunotherapy.

PMID- 15151754
TI  - [Reparative and therapeutic effect of rhBMP-2m on mice injured by chemotherapy].
AB  - AIM: To probe the therapeutic effect of recombinant human bone marrow
      morphogenetic protein-2 maturation peptide(rhBMP-2m) on mouse bone marrow injury
      caused by cyclophosphamide (CTX). METHODS: 18 mice were divided randomly into 3
      groups, namely CTX injection group(CTX group), BMP therapy group(BMP group) and
      PBS control group(Control group), 6 mice each group. CTX of 200 mg/kg per mouse
      was intraperitonealy(IP) injected at a time to BMP group and CTX group so as to
      establish the experimental model of mouse bone marrow injury. In BMP group, the
      therapy started from the second day after injection of CTX by using IP injection
      of 0.5 mg BMP per mouse each day. In control group, PBS was injected only.
      Changes of peripheral blood leukocyte numbers in 3 groups were observed. On the
      5th and 8th day after CTX injection, DNA content in mouse bone marrow karyocytes
      and variation of cell cycle were analysed by flow cytometry(FCM). Colony forming
      unit granulocyte-macrophage(CFU-GM) was cultivated simultaneously. RESULTS: On
      the 4th day after injection of CTX, the leukocyte number in mouse peripheral
      blood of CTX group dropped to the lowest level, and then picking up gradually. In
      respect to the variation of the leukocyte number, there was no significant
      difference between BMP group and CTX group (P>0.05). On the 5th day, the ratio of
      G(0)/G(1) phase cells in BMP group was notably higher than that of CTX group, and
      the necrotic and apoptotic rates decreased markedly (P<0.01). On the 8th day, the
      number of karyocytes in mouse bone marrow of BMP group was obviously more than
      that of CTX group (P<0.01). CONCLUSION: BMP has some therapeutic effect on mouse
      bone marrow injury caused by CTX.

PMID- 15151755
TI  - [Study of NMDAR expression in hippocampal CA(1) region in neonatal rats with
      hypoxic-ischemia].
AB  - AIM: To study the expressions of NMDAR in hippocampal CA(1) region after hypoxic
      ischemic brain damage(HIBD) in neonatal rats. METHODS: An neonatal rat model with
      hypoxic-ischemic brain damage was set up. The expression of NMDAR was detected in
      normal control and hypoxic-ischemic (HI) brain damage group by
      immunohistochemical staining and in situs hybridization. RESULTS: The number of
      NR1(+) and NR1 mRNA(+) cells decreased slightly in hippocampal CA(1) region at 2
      h after HI. The numbers increased from 24 h to 48 h after HI, and reached maximum
      at 72 h after HI. CONCLUSION: NR1 expressed in hippocampal CA(1) region of normal
      neonatal rats, and the expression is up-regulated after HI brain injury.

PMID- 15151756
TI  - [Expression of a secreted fusion protein consisting of anti-HER2 antibody and
      reversed caspase-3 and its suppression on growth of SKOV3 cells].
AB  - AIM: To investigate the killing effect on SKOV3 cells by fusion protein HER2
      specific antibody-reversed caspase-3 in the secreted form. METHODS: The reversed
      human caspase-3 gene was subcloned into pCMV-e23scFv-PEII-PEIII to construct
      recombinant eukaryotic expression vector pCMV-e23scFv-PEII-revcasp-3 and
      transfect Jurkat cells. The secreted expression of the in culture supernatant of
      transfected Jurkat cells was detected by ELISA. The suppression of the fusion
      protein on growth of SKOV3 cells was examined by co-culture with supernatant of
      transfected Jurkat cells. RESULTS: There was the secreted expression of the
      fusion protein in Jurkat cells. Expressed product had the activity of inducing
      SKOV3 cells to death. CONCLUSION: The fusion protein expressed in the secreted
      form can targeted towards SKOV3 cells and kill them.

PMID- 15151757
TI  - [Construction of single-chain Fv Gene of Anti-HBsAg and its expression in COS-7
      cells].
AB  - AIM: To subclone the V(L) gene and V(H) genes of anti-HBsAg and construct the
      single-chain Fv gene and to analyse the expression of the constructed gene in COS
      7 cells. METHODS: A set of oligonucleotide primers were designed and used to
      amplify the V(H) and V(L) genes from Fab antibodies screened from phage antibody
      library. The products were cloned into pUC19 vector and their sequences were
      analysed. The V(H) and V(L) gene fragments were linked up by a peptide linker and
      a leader sequence added at 5' terminus of each gene (L-V(H)-Linker-V(L)) and
      designated as L-ScFv. The L-ScFv genes were inserted into the eukaryotic fusion
      protein expression vector pEGFP-N3 and transfected into COS-7 cells to express
      respectively. RESULTS: The coding sequences of V(H),V(L), linker and leader in
      all constructs were all correct. The expression of ScFv fusion protein was
      detectable by fluorescence microscope after transient expression in COS-7. The
      secretive expression of L-ScFv was confirmed by SDS-PAGE and Western blot
      analysis. And the binding specificity of the ScFvs with HBsAg were proved by
      indirect ELISA. CONCLUSIONS: Anti-HBsAg ScFv genes have been successfully
      constructed and expressed in COS-7 cells.

PMID- 15151758
TI  - [Preparation and characterization of monoclonal antibodies against human
      transmembrane activator and calcium modulator and cyclophilin ligand interactor].
AB  - AIM: To prepare monoclonal antibodies against human TACI and study the
      distribution of TACI on peripheral blood nuclear cells(PBMCs). METHODS: Murine
      mAbs were prepared by hybridoma technique. The distribution of TACI on PBMCs were
      identified by immunofluorescence staining, FCM analysis as well as
      immunohistochemical staining. RESULTS: Two hybridoma cell lines secreting mAbs
      against TACI were obtained. The titers of ascitic mAbs was 10(-7) and their Ig
      subclasses were IgG1. Both could recognize natural TACI on T cells. In the PHA
      activated models, TACI was expressed mainly on activated CD4(+) T cells.
      CONCLUSION: Two mAbs can recognize natural TACI, which will be of greater value
      in research on the structure and functions of TACI.

PMID- 15151759
TI  - [Preparation, characterization and application of monoclonal antibodies to Fc
      fragment of Ig fusion protein].
AB  - AIM: To prepare and characterize mAb to Fc fragment of Ig fusion protein, and to
      establish sandwich ELISA for detecting Ig fusion proteins and affinity
      chromatography method for Ig fusion protein purification. METHODS: hBCMA-Ig was
      used as antigen to immune BALB/c mice. The lymphocyte hybridoma technique was
      used to establish hybridoma cell lines stably secreting anti-Fc mAb. ELISA was
      employed to detect the isotype, epitopes, and species specificity of mAbs.
      Western blot was used to assess the reactivity between anti-Fc mAbs and denatured
      Ig fusion protein. LAIR1-Ig fusion protein was purified through affinity column
      anti-Fc mAb cross-linked to Sepharose 4B. RESULTS: Seven hybridoma cell
      lines(FMUFc1-FMUFc7) were acquired. A sandwich ELISA was successfully established
      using FMUFc4 as coating mAb and FMUFc5 as enzyme-labeled mAb. FMUFc6 could be
      used for Western blot. LAIR1-Ig fusion protein was effectively purified through
      FMUFc5-Sepharose affinity chromatography column. CONCLUSION: mAb against Fc
      fragment of Ig fusion protein has been prepared successfully, and methods to
      detect and purify Ig fusion protein are established. These mAbs provide useful
      tool for further application of Ig fusion protein.

PMID- 15151760
TI  - [Preparation of monoclonal antibodies against neurotoxic agent raised from an
      organophosphorus hapten and its characterization].
AB  - AIM: To develop monoclonal antibodies(mAbs) against a novel hapten, pinacolyl 1-p
      aminophenyl-1-hydroxymethylphosphonate(P4). METHODS: P4 was coupled chemically
      with Limulus polyphemus hemocyanin (LPH) to form a coupling agent P4-LPH, and
      then BALB/c mice were immunized with the P4-LPH. MAbs were prepared by hybridoma
      technique. Cross reactivities of mAbs to 7 ligands were detected by competitive
      inhibition enzyme immunoassay. The cross reactiveities were expressed by the
      concentration of ligand which inhibited 50% reaction of mAbs(IC(50)). RESULTS:
      Nine mAbs were developed. Eight of them were specific for P4, four (1B3, 2B2, 3D5
      and 4F1) could react to soman, their IC(50) were 10(-3), 10(-3), 10(-5) and 10(
      6) mol/L respectively, and one (4F1) could recognize paraoxon, IC(50) being 10(
      5) mol/L. All of which were effective with a titer as high as 10(6) to 10(8) in
      dilution. CONCLUSION: mAbs specific for soman and paraoxon are developed
      successfully, which may be used for research on soman abzyme, immuno
      detoxification of soman poisoning and immunoassay for soman or/and paraoxon.

PMID- 15151762
TI  - [Inhibition of momordica anti-HIV protein of MAP30 on HBeAg expression by laser
      scanning confocal microscopy].
AB  - AIM: To investigate the effect of momordica anti-HIV protein of M(r ) being 30
      000 (MAP30) on HBV expression by laser scanning confocal microscopy. METHODS: HBV
      DNA-transfected hepatocarcinoma cells 2.2.15 were cultured in the presence of
      MAP30. Then quantitative analysis of HBeAg expression in the 2.2.15 cells by
      laser scanning confocal microscopy after indirect immunofluorescence staining was
      performed. RESULTS: The fluorescence intensity in 2.2.15 cells co-cultured with
      MAP30 was notably weaker than that in control cells. CONCLUSION: MAP30 can
      effectively inhibit HBeAg expression in the 2.2.15 cells.

PMID- 15151761
TI  - [Development and application of an indirect immunofluorescence assay for the
      detection of serum immunoglobulin G to human herpesvirus 6].
AB  - AIM: To establish an indirect immunofluorescence assay(IFA) for detection of
      serum IgG antibody against human herpesvirus 6(HHV-6). METHODS: Cord blood
      mononuclear cells infected by HHV-6 strain CN(5) were used to prepare cell
      antigen smear, so as to establish an IFA and make an epidemical investigation on
      serum specimens of child-bearing age, women. RESULTS: The specificity of the IFA
      for HHV-6 was confirmed by absorption assay(test). The IFA detection showed that
      in serum specimens from 116 cases of child-bearing age, women, the positive rate
      of anti-HHV-6 IgG was 72.4% and geometric mean titer(GMT) was 1:61. The positive
      rate and GMT of serum anti-HHV-6 IgG had no differences between pregnant women
      and unpregnant women, neither among pregnant women at different pregnant stages.
      CONCLUSION: A specific IFA has been developed successfully for epidemical
      investigation of HHV-6 infection rate in child-bearing women.

PMID- 15151763
TI  - [The significance of fluorescent patterns of antineutrophil cytoplasmic
      antibodies (ANCA) in renal diseases].
AB  - AIM: To further explore significance of fluorescent patterns of antineutrophil
      cytoplasmic antibodies in renal diseases. METHODS: ANCA fluorescent patterns and
      its target antigens in sera of 251 patients with renal diseases were detected by
      indirect immunofluorescence (IIF) and ELISA. RESULTS: The positive percentage of
      ANCA is 20.3% (51/251), in which 3.98%(10/251) is cANCA, 11.95% (30/251) pANCA
      and 4.38%(11/251) aANCA. CONCLUSION: The simultaneous screening for ANCA and its
      target antigens by IIF and ELISA can increase the positive percentage of ANCA in
      renal diseases. This novel screening strategy is able to distinguish atypical
      ANCA(aANCA) from pANCA with ANA and therefore useful for differential diagnosis
      between vasculitis and autoimmune diseases.

PMID- 15151764
TI  - [Effect of granulocyte colony-stimulating factor on the ratio of peripheral blood
      dendritic cell subsets].
AB  - AIM: To clarify the effect of granulocyte colony-stimulating factor (G-CSF) on
      the radio of two peripheral blood dendritic cell(DC) subsets in-vivo. METHODS:
      Various doses (0, 5, 10 and 15 microg) of G-CSF were subcutaneosly injected
      respectively into BALB/c mice, once each day, for 6 days running. Six days later,
      DCs were separated from peripheral blood. Then the flow cytometry was used to
      detect the radio of DC1 and DC2 (CD11c(+) CD8a(-) and CD11c(+) CD8a(+)), and to
      calculate their absolute numbers. RESULTS: After stimulation with varying doses
      of G-CSF for 6 days, the absolute number of DC2s increased from 9.6x10(6)/L to
      55.1x10(6)/L (P<0.01), while that of DC1s had no notably variation, so the ratio
      of DC1 and DC2 decreases from 4.2+/-1.1 to 0.7+/-0.3 (P<0.01). CONCLUSION: G-CSF
      can increase the absolute number of peripheral blood DC2s, but has no influence
      on peripheral blood DC1 number, thus inversing the ratio of DC1/DC2 in-vivo.

PMID- 15151765
TI  - [Establishment of a sandwich ELISA for detecting serum sTRAIL and its
      application].
AB  - AIM: To establish quantitative ELISA for detecting souble TRAIL and to evaluate
      its clinical application. METHODS: The mAb FMU1.1 against TRAIL was used as
      coating antibody, and the rabbit polyclonal antibody to TRAIL as a sandwich
      antibody. The serum sTRAIL levels of nine patients with hemorrhagic fever with
      renal syndrome and forty psoriasis patients were measured by this method.
      RESUITS: Sandwich ELISA was established by combination of mAb and pAb. The
      sensitivity of the ELISA was 0.08 microg/L. The increased levels of serum sTRAIL
      were found in three cases out of nine HFRS patients and eight cases out of forty
      psoriasis patients. CONCLUSION: A sandwich ELISA is developed, which provide an
      useful tool judging the patients condition, curable effect and prognosis of some
      related diseases.

PMID- 15151766
TI  - [Development and preliminary application of a double mAb sandwich ELISA for
      detecting soluble CD226].
AB  - AIM: To develop a double mAb sandwich ELISA for detecting sCD226 and apply it to
      clinical specimens. METHODS: The optimal concentrations of coating mAb and HRP
      mAb, and the optimal diluents were determined. A double mAb sandwich ELISA then
      was established. The specificity, sentivity and stability of the method were
      identified. And clinical specimens were detected by this method. RESULTS: The
      optimal concentrations of coating mAb LeoA1 and HRP-mAb FMU3 were 2.5 mg/L and
      1:400, respectively, and the optimal diluents for standard antigen and HRP-mAb
      were 1 g/L BSA 1 mL/L Tween20-PBS and 30 g/L PEG-PBS.The ELISA achieved
      satisfactory results in respect to specificity (no cross-reaction to human IgG,
      in block test blocking effect was does-dependent), sensitivity (the detected
      threshold was 110 ng/L) and stability (CV<10.2%). Statistical analysis showed
      that the serum sCD226 level in patients with rheumatoid arthritis (RA) was
      significantly higher than that in healthy adults. CONCLUSION: A double mAb
      sandwich ELISA with high specifity, and relative sensitivity for detection of
      sCD226 has been developed. It is shown to be an applicable method of detecting
      sCD226 in clinical specimens.

PMID- 15151767
TI  - [Interaction between p53 and HSP70 in human hepatocellular carcinoma tissues].
AB  - AIM: To investigate the interaction between p53 and heat shock protein70 (HSP70)
      in human hepatocellular carcinoma tissues. METHODS: HSP70 and p53-double positive
      samples were screened by imunohistochemical staining from twelve human
      hepatocellular carcinoma tissues, and the tissue homogenate was prepared.
      Coimmunoprecipitation was performed by using either anti-HSP70 mAb or anti-p53
      mAb. The immunoprecipitate was analysed by SDS-PAGE and Western blot. RESULTS:
      Immunohistochemical staining detection showed that three samples out of twelve
      cases were double positive for both HSP70 and p53. p53 protein existed in the
      immunoprecipitate of anti-HSP70 mAb, while there was HSP70 protein in the
      immunoprecipitate of anti-p53 mAb. CONCLUSION: HSP70 and p53 exist as a complex
      in human hepatocellular carcinoma tissues, which will provide a new route for
      studying the pathogenesis and immunotherapy of human hepatocellular carcinoma.

PMID- 15151768
TI  - [The study of primary culture methods for hippocampal neurons of newborn rats].
AB  - AIM: To compare three different methods for neuron culture, so as to provide a
      culture technique with higher neuron purity and survival rate. METHODS: Neurons
      in hippocampal region of newborn SD rats were cultured by common culture method,
      cytosine arabinoside (Ara-c)-supplementing method, Ara-c and nerve growth factor
      (NGF)-supplementing method. Then morphology of neurons was observed under
      microscope. The survival rates of the neurons at different culture times were
      compared by inverted microscope observation and MTT colorimetry. The purity of
      neurons cultured by 3 methods was detected by immunocytochemical staining.
      RESULTS: Neurons cultured by Ara-c and NGF-supplementing method grew well. The
      purity and survival rate of neurons cultured by Ara-c and NGF-supplementing
      method was highest. CONCLUSION: Ara-c and NGF-supplementing method is a good
      method for neuron culture.

PMID- 15151769
TI  - [Atherosclerotic coronary artery disease: usefulness of C-reactive protein for
      the identification of the vulnerable plaque and the vulnerable patient].

PMID- 15151770
TI  - [Why does magnetic resonance imaging remain underused in patients with heart
      disease?].

PMID- 15151771
TI  - [Relationship of C-reactive protein levels with angiographic findings and markers
      of necrosis in non-ST-segment elevation acute coronary syndrome].
AB  - INTRODUCTION AND OBJECTIVES: The mechanism responsible for elevated C-reactive
      protein levels (inflammation of the ruptured atherosclerotic plaque or myocardial
      necrosis) in acute coronary syndromes is controversial. The aim of this study was
      to investigate the relationship between C-reactive protein levels and
      angiographic complexity of the culprit lesion and troponin elevation in patients
      with non-ST elevation acute coronary syndromes. PATIENTS AND METHOD: The study
      group consisted of 125 patients with single-vessel disease. Troponin-I and C
      reactive protein were measured, and the complexity of the culprit lesion was
      analyzed (TIMI flow and thrombus). Information on age, sex, smoking habit,
      hypertension, hypercholesterolemia and diabetes was obtained from the medical
      record. RESULTS: The quartile distribution of C-reactive protein showed more
      patients with TIMI flow < 3 (31%, 28%, 18%, and 55%; P=.02), thrombus (3%, 6%,
      7%, and 28%; P=.007) and troponin-I elevation (19%, 44%, 50%, and 66%; P=.003) in
      the fourth quartile. Multivariate analysis showed both thrombus (OR = 4.1; 95%
      CI, 1.2-14.3; P=.03) and troponin elevation (OR = 2.6; 95% CI, 1.1-6.3; P=.03) to
      be associated with C-reactive protein > 18 mg/L (fourth quartile cut-off). When
      treated as a continuous variable, higher levels of C-reactive protein were also
      associated with thrombus (P=.02) and troponin elevation (P=.003). No other
      clinical variables were related with C-reactive protein levels. CONCLUSIONS: Both
      angiographic complexity of the culprit lesion and elevated troponin level are
      related with increased C-reactive protein levels in non-ST elevation acute
      coronary syndromes.

PMID- 15151772
TI  - [Assessment of myocardial perfusion by cardiovascular magnetic resonance:
      comparison with coronary angiography].
AB  - INTRODUCTION AND OBJECTIVES: The assessment of regional myocardial perfusion by
      cardiovascular magnetic resonance imaging makes it possible to detect significant
      coronary artery lesions. The purpose of this study was to determine the
      usefulness of this technique in non-selected patients with ischemic heart
      disease. PATIENTS AND METHOD: The study group included 32 patients (26 men; mean
      age: 65 years old). Gadolinium (0.05 mmol/kg) for first-pass imaging was
      administered through a peripheral vein, both at rest and after adenosine infusion
      (140 mg/kg for 6 min). The presence of a regional perfusion defect was assessed
      visually, and these images were compared against coronary angiographic images.
      RESULTS: Angiography showed 49 significant (> 70%) obstructive lesions in a
      coronary artery. Magnetic resonance showed a perfusion defect at rest (fixed) in
      35 myocardial segments, and only after adenosine infusion (reversible) in 16
      additional regions, for a total of 51 segments with perfusion defect. Sensitivity
      for the detection of an angiographically significant coronary lesion was 78%,
      with a specificity of 75%. These figures decreased to 54% and 65%, respectively,
      when only fixed defects were considered. There were no visible defects in 26% of
      the myocardial territories with proven previous necrosis, although effective
      reperfusion and patent culprit arteries were frequently seen in these cases.
      CONCLUSIONS: The detection of a regional myocardial perfusion defect by visual
      analysis with first-pass gadolinium and cardiovascular magnetic resonance imaging
      shows good diagnostic accuracy for the presence of significant coronary artery
      obstruction, provided that both rest and pharmacological stress studies are
      performed.

PMID- 15151774
TI  - [Comparison of intracoronary ultrasound expansion parameters in coronary stents
      implanted with or without balloon predilatation. A randomized intravascular
      ultrasound study].
AB  - INTRODUCTION AND OBJECTIVES: Coronary stenting without balloon predilatation is a
      safe technique associated with similar clinical results and lower costs, use of
      contrast and exposure to radiation in comparison to stenting with predilatation.
      After direct stenting, expansion may be reduced if the stenotic lesion was not
      predilatated. This study compared a). stent expansion with and without balloon
      predilatation (direct stenting), observed by intracoronary ultrasound, and b).
      angiographic results after 6 months and 1 year with the two implantation
      techniques. PATIENTS AND METHOD: 100 consecutive lesions eligible for direct
      stenting were randomized to stent implantation with or without balloon
      predilatation. Only <or=25 mm Multilink Duet/Tri-Star/Tetra or NIR Sox/Elite
      stents were used. When the angiographic result was considered optimal, an
      independent operator who had not been involved in the procedure performed an
      intracoronary ultrasound study. The ultrasound examination was not used in
      decision making unless there was a potential risk for the patient. Ultrasound
      parameters of expansion were compared in the two implantation techniques with
      systematic 6- to 9-month angiographic examinations and 1-year clinical follow-up.
      RESULTS: There were no clinical or baseline angiographic differences between the
      two groups. No significant differences were observed in the ultrasound expansion
      parameters or the rate of clinical events after 12 months of follow-up. Binary
      angiographic restenosis (23% vs 20%) and late loss index (0.92 [0.81] vs 0.88
      [0.60]) did not differ significantly between the predilatation and direct
      stenting groups. CONCLUSIONS: Direct stenting was not associated with different
      ultrasound expansion parameters in comparison to the conventional technique.
      Angiographic restenosis and the rate of long-term clinical events were similar
      with both techniques.

PMID- 15151773
TI  - [NT-proBNP levels and hypertension. Their importance in the diagnosis of heart
      failure].
AB  - INTRODUCTION: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in
      the diagnosis of heart failure. We compared NT-proBNP levels in patients with and
      without a diagnosis of arterial hypertension. PATIENTS AND METHOD: Participants
      were recruited from a random sample of 999 inhabitants from the Community of
      Valencia (eastern Spain). Of these patients, 432 said they suffered from dyspnea
      and were referred to their hospital (10 hospitals involved), where blood samples
      were taken, an echo-Doppler study was performed, and the patients completed a
      questionnaire. Of the 432 participants with dyspnea, 215 gave informed consent
      for their inclusion in the study, and 202 completed the study. Hypertension was
      diagnosed in 72 participants and 130 were normotensive. RESULTS: For the whole
      population, NT-proBNP, expressed as the median and range, was 88 (0-2586) pg/mL.
      When we compared hypertensive with normotensive participants, we found higher NT
      proBNP levels in the former group: median 123, range 0-2184 pg/mL, versus median
      77, range 0-2586 pg/mL (P<.01). When we excluded subjects with systolic left
      ventricular dysfunction, we found higher levels in participants with
      hypertension: 119 (0-2184 pg/mL) vs 72 (0-997 pg/mL) (P<.01). When we also
      excluded subjects with diastolic dysfunction, we found (median 85, range 0-430
      pg/mL) and (median 66, range 0-997 pg/mL), respectively (p = NS). CONCLUSION: In
      a population study of subjects with dyspnea, hypertensive patients have higher NT
      proBNP levels than subjects with normal blood pressure. This difference
      disappeared when patients with diastolic dysfunction were excluded from the
      analysis. Hypertension can thus be a confounding factor that potentially
      decreases the specificity of NT-proBNP levels for the diagnosis of heart failure.
      These findings should be taken into account when conducting clinical and
      epidemiological studies in which patients with both heart failure and
      hypertension are included.

PMID- 15151775
TI  - [Aortic root homograft in the surgical treatment of aortic valve disease with
      dilated ascending aorta].
AB  - INTRODUCTION AND OBJECTIVES: Patients with aortic valve disease and a dilated
      ascending aorta are usually treated with a composite graft comprising a valve and
      conduit. We review here the results of treatment with an aortic root homograft as
      a valid alternative. PATIENTS AND METHOD: Twenty-two consecutive patients with a
      mean age of 64.8 (8.8) years were studied. Mean ascending aorta dilation was
      54.55 mm, aortic valve insufficiency was present in 16 patients, and a combined
      lesion was present in 6. In all cases a cryopreserved aortic root homograft was
      used to replace the aortic valve and ascending aorta. In 9 cases a Dacron conduit
      was used beyond the sinotubular junction to restore continuity between the
      homograft and the native aorta. RESULTS: All patients survived surgery. One
      patient had postoperative systemic inflammatory response syndrome and one patient
      was re-explored for excessive bleeding. Mean duration of follow-up was 12.1
      months (range 2-36 months). No patient was given anticoagulants, and one had an
      early transient cerebrovascular accident followed by complete recovery. At one
      month postsurgery the left ventricular systolic (P<.001) and diastolic (P<.009)
      diameters had decreased significantly on echocardiography, and these decreases
      persisted throughout follow-up. The caliber of the ascending aorta was normal in
      all patients (< or =30 mm) except one. CONCLUSIONS: Aortic root homografts are a
      valid alternative in the treatment of aortic valve disease with ascending aorta
      dilation. The main advantages of this therapy are that permanent anticoagulation
      is not needed, and that left ventricular dimensions recover rapidly.

PMID- 15151777
TI  - [Inflammation in acute coronary syndromes: mechanisms and clinical implications].
AB  - Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and its
      complications. In particular, atherosclerosis is an active process and the
      inflammatory component appears to be particularly correlated with the development
      of acute coronary syndromes (ACS). Accumulating data demonstrate that in ACS,
      elevated levels of circulating inflammatory markers, such as C-reactive protein,
      predict an unfavorable cardiovascular outcome. A better knowledge of the
      molecular and cellular mechanisms of inflammation might not only further improve
      prognostic stratification but also allow us to identify novel therapeutic
      targets. The present review summarizes the mechanisms of the inflammatory
      response in ACS, its clinical implications, and the potential treatment
      strategies to contrast this phenomenon.

PMID- 15151778
TI  - [Rationale and clinical evidence for the effects of new pharmacological
      treatments for heart failure].
AB  - Congestive heart failure is a leading cause of cardiovascular morbidity and
      mortality, and is the main cause of hospitalization among patients older than 65
      years. Moreover, its prevalence is expected to reach nearly epidemic proportions,
      so that the need for new treatments is clear. In this article we review current
      and future strategies for the treatment of systolic heart failure that are based
      on a better understanding of the pathophysiology of this disorder and on the
      results of controlled clinical trials of different treatments. Drugs under
      development (phase II and III clinical trials) have been classified into four
      main groups: neurohumoral antagonists, inotropic agents, modulators of myocardial
      remodeling, and future approaches to treatment such as gene therapy and anti
      apoptotic drugs. We also discuss new strategies for the treatment of diastolic
      heart failure.

PMID- 15151779
TI  - [Pulmonary artery aneurysm].

PMID- 15151780
TI  - [Percutaneous closure of ventricular septal defect with an Amplatzer device].
AB  - We present a series of 4 patients in whom a ventricular septal defect (VSD) was
      closed with an Amplatzer muscular VSD device during cardiac catheterization. In
      one patient with type I truncus arteriosus and subarterial VSD, closure of a wide
      apical defect was done to allow further surgical correction while avoiding left
      ventricular ventriculotomy. The second patient had congenitally corrected
      transposition of the great arteries with complete A-V block and a pacemaker
      implanted from birth. Our intention was unload the systemic anatomical right
      ventricle. The third patient had had 3 heart surgeries to correct a double outlet
      right ventricle. She had a residual ventricular septal defect which was large
      enough to cause heart failure. The last patient had an isolated muscular
      ventricular septal defect. Percutaneous closure was successful in all patients,
      and there were no complications. Percutaneous closure of the defect may be used
      as a primary procedure, before surgery, or as a complementary procedure after
      surgery.

PMID- 15151782
TI  - [Myocardial infarction and 5,10-methylenetetrahydro-folate reductase mutation].
AB  - A 40-year-old woman with previous venous thrombosis in the lower limbs had
      recurrent myocardial infarction in the early puerperium. The only documented risk
      factor was an elevated level of plasma homocysteine, associated to a
      heterozygotic anomaly in the enzyme responsible for its metabolism, 5,10
      methylenetetrahydrofolate reductase. The case and approaches to treatment are
      discussed.

PMID- 15151781
TI  - [Neurohormonal prediction of post-infarction ventricular dysfunction and coronary
      disease].
AB  - Little information is available about the potential role of brain (type B)
      natriuretic peptide in patients with acute myocardial infarction. We therefore
      analyzed peptide levels, measured at discharge from our coronary care unit, in 56
      patients admitted with a diagnosis of acute myocardial infarction. We examined
      peptide concentrations in the light of different features in our patients, and
      found a significant association between natriuretic peptide levels and the two
      most important prognostic factors: left ventricular ejection fraction, and the
      severity and extent of coronary disease. Type B natriuretic peptide was a good
      predictor of these features, and we conclude that concentration of type B
      natriuretic peptide, measured at discharge from the coronary care unit, provides
      important clinical and prognostic information in patients with acute myocardial
      infarction.

PMID- 15151783
TI  - [Arrhythmia induction during atrial pacing with atrial floating electrodes].
AB  - Atrial pacing with floating electrodes primarily designed for single lead VDD
      systems has disadvantages attributable to the floatability of the electrodes.
      Body and breathing movements cause changes in the position of the atrial dipole
      that can lead to failure of atrial capture and sensing, and even alternation of
      the stimulated chamber. We report the induction of typical intranodal tachycardia
      episodes related to intermittent failure of atrial capture in a patient with an
      implanted single lead DDD pacing system. Such systems pose a substantial risk of
      potentially arrhythmogenic asynchronous pacing.

PMID- 15151784
TI  - [Cardiac defects in Mexican children with down syndrome].

PMID- 15151786
TI  - [Care of the elderly in primary care. Need for training].

PMID- 15151789
TI  - [Functional ability and social-care problems of the elderly in the Caceres health
      area].
AB  - OBJECTIVE: To describe the social environment and to identify the health problems
      and the functional and mental ability of the elderly in the community. DESIGN:
      Cross-sectional, observational study by means of a questionnaire. PATIENTS: 228
      people over 71 and not living in an institution. SETTING: Caceres Health Area.
      MAIN MEASUREMENTS: Questionnaire on social and demographic details, main
      pathologies, social assessment (Gijon scale), functional assessment (Barthel and
      Lawton-Brody scales), mental assessment (Pfeiffer test), geriatric problems and
      visits from health professionals. RESULTS: 67% of the 228 people in the sample
      were women, with an average age of 79. Comorbidity, present in over 70% of the
      elderly, was significantly related to multi-medication, falls, hospital
      admission, depression and insomnia. The most common social and family situation
      was of a person living with his/her partner (38.3%; CI, 6.31) or children, in a
      dwelling with architectural barriers (43.0%; CI, 6.43), with a good relationship
      to his/her social surroundings (61.0%; CI, 6.33). The Barthel test showed a
      significant relationship with all the geriatric problems declared. The Pfeiffer
      test showed a relationship with falls (t=3.10; P=.00214), with hearing problems
      (t=1.98; P=.048), with incontinence (t=3.59; P=.0040) and constipation (t=2.64;
      P=.0086). The Lawton-Brody test was related, in women, with falls (t=4.27;
      P=.00034), admissions (t=2.02; P=.044), constipation and sight and hearing
      problems; and in men, with depression and incontinence. CONCLUSIONS: Elderly
      people in the Caceres Health Area showed good functional ability in their basic
      daily tasks, less ability in instrumental activities and high comorbidity.

PMID- 15151787
TI  - [Use of the Goldberg General Health Questionnaire (GHQ-28) to detect psychosocial
      problems in the family physician's office].
AB  - OBJECTIVE: To analyze the usefulness of the 28-item Goldberg General Health
      Questionnaire (GHQ-28) in identifying psychosocial problems, and to determine how
      the questionnaire scores are related to stressful life events (SLE), use of
      health services, and individual variables (age, sex, employment status,
      socioeconomic group, and educational level). DESIGN: Cross-sectional study.
      SETTING: Almanjayar Health Center in the city of Granada, Southern Spain.
      PARTICIPANTS: 314 patients more than 18 years of age, selected by systematic
      sampling at an on-demand health center. MAIN MEASURES: Each patient completed the
      GHQ-28 during the course of a personal interview, and scores of 8 or higher were
      considered to indicate psychosocial problems. Score on the Social Readjustment
      Rating Scale of Holmes and Rahe (stressful life events during the previous year)
      was also recorded, as were socioeconomic group, educational level, employment
      status and use of services (number of visits to the doctor during the previous
      year). All variables were subjected to descriptive analysis and their
      associations with the GHQ-28 score were tested with the chi-squared test.
      Multivariate analysis was used to identify categories that showed an independent
      association with high scores on the GHQ-28. RESULTS: The variables associated
      with a greater likelihood of psychosocial problems were female sex (OR, 2.15; CI,
      1.14-4.04) and high levels of stress (OR, 2.65; CI, 1.50-4.68). Both showed a
      statistically significant association with the GHQ-28 score after multivariate
      analysis. CONCLUSIONS: The GHQ-28 is a potentially useful instrument to detect
      psychosocial problems in the family physician's office, and can aid in the
      subsequent identification and qualitative evaluation of patients.

PMID- 15151790
TI  - [Measuring health-related quality of life in children and adolescents:
      preliminary validation and reliability of the Spanish version of the KINDL
      questionnaire].
AB  - OBJECTIVES: To obtain a first Spanish version of the KINDL questionnaire
      idiomatic and culturally equivalent to the German original version, and then to
      evaluate its psychometric properties in a sample of healthy children/adolescents
      8-16 years old, and their parents. DESIGN: Cross-sectional study. SETTING: 2
      public schools of Asturias of similar sociodemographic conditions. PARTICIPANTS:
      243 children 8-16 year-old, and 153 parents were investigated. MAIN MEASUREMENTS:
      HRQoL evaluated through the generic questionnaire KINDL. An external assessment
      through the parents was made as well. The psychometric properties of the Spanish
      version of the questionnaire were investigated and results on HRQoL are presented
      for different ages and gender in the Spanish sample. RESULTS: 6 items (6/24)
      needed successive translations and conceptual discussion during the phase of
      idiomatic adaptation. The factorial analysis confirmed the validity of
      construction of the instrument for most scales. The internal consistency,
      measured by alpha Cronbach coefficent, was good for the total of the
      questionnaire (>0.70) and acceptable in most of the scales (>0.50). Only the
      school scale for adolescents shows very poor reliability. Females and children
      with higher age scored lower in most of the investigated dimensions (P<.01).
      CONCLUSIONS: The first Spanish version of the Kindl showed acceptable reliability
      and validity. In spite of the punctual inadequacies found in this first step of
      the investigation, the results constitute an important starting point to work
      further on the KINDL as an HRQoL instrument--in Spanish language--to measure
      subjective well-being in children.

PMID- 15151791
TI  - [Efficacy of an intervention to improve treatment compliance in hyperlipidemias].
AB  - OBJECTIVE: To analyse the efficacy of the intervention through a telephone call
      about patients' compliance with lipaemia therapy. DESIGN: Controlled, randomised
      clinical trial. SETTING: Ten clinics at 6 primary care centres. PARTICIPANTS: 126
      people diagnosed with hypercholesterolaemia according to Spanish Consensus
      criteria were chosen. INTERVENTION: Two groups were formed. The control group
      (CG) of 63 patients, who received the doctor's normal treatment; and the
      Intervention group (IG) of 63 patients, who received in addition a telephone call
      at 2 weeks, 2 months and 4 months. MAIN MEASUREMENTS: Pills were counted and
      cholesterol, triglycerides, HDL-C and LDL-C determined at the start, and at the
      third and sixth months. Percentages of patients complying (80%-110%), the mean
      compliance percentage and the degree of control were compared. The reduction of
      absolute and relative risk (RAR and RRR) and the mean number of people that
      required an intervention in order to avoid non-compliance (NI) were calculated.
      RESULTS: 115 people (91.26%) completed the survey, 56 in the IG and 59 in the CG.
      77.1% complied with the therapy (CI, 68.4-85.8), (CG=64.4%, CI, 55.3-73.5;
      IG=93.5%, CI, 88.8-98 [P<.001]). Mean compliance ran at 88.7 +/- 10.2 overall, at
      84.4 +/- 12.8 in the CG and at 93 +/- 8.2 in the IG (P<.001). The RAR was 29.1%,
      the RRR 81%, and the NI was 3.43 patients. The patients controlled ran at 43.9%
      in the IG (CI, 34.9-52.9) and 23.1% in the CG (CI, 15.4-30.8) (P<.005).
      CONCLUSIONS: The telephone intervention is an efficacious way of improving the
      percentage of patients complying with lipaemia treatment.

PMID- 15151792
TI  - [Patients on multiple medication: do they know the right doses? Do they take
      their medications correctly?].
AB  - OBJECTIVES: To find whether patients on multiple medication attending our
      consultations know the doses of the medication prescribed them. To verify whether
      these patients say they have taken the prescribed medication correctly. DESIGN:
      Descriptive study through questionnaire given the patient or the carer
      responsible for the medication. SETTING: Health centre in the periphery of our
      city. PARTICIPANTS: 212 patients (104 men and 108 women) under 65 years old and
      228 (118 men and 110 women) over this age, under treatment with medication taken
      orally, rectally or transdermically. MAIN MEASUREMENTS: Questionnaire in which
      two questions were asked orally of the patient or carer on each of the medicines
      prescribed (between 1 and 9): a) how has your doctor said you should take the
      medicine, and b) how do you really take the medicine? The replies were noted down
      by the interviewer and then evaluated when the data were checked against the
      clinical records. RESULTS: Only 20% of those under 65 who took 8 or 9 medicines
      remembered correctly the dosages of all of them. 10% of those who took 9
      medicines said they took them correctly. 30% of those over 65 who took 8
      medicines knew the dosages of all of them. 10% of those who took 9 medicines and
      20% of those who took 8 said they took them all correctly. CONCLUSIONS: In the
      case of patients on multiple medication, the doctor must try to establish simple
      dosage patterns (once or twice a day) of the most efficient efficacious
      medication.

PMID- 15151793
TI  - [Family medicine and waiting lists].

PMID- 15151795
TI  - [Quality of life for patients with chronic obstructive pulmonary disease and
      oxygen therapy at home].

PMID- 15151794
TI  - [The manager-clinician relationships: a perspective from primary care
      physicians].

PMID- 15151796
TI  - [Effectiveness of "was there anything else?" as a way of preventing additional
      demands].

PMID- 15151797
TI  - [Hyponatremia due to carbamazepine and paroxetine].

PMID- 15151798
TI  - [Lipoid necrobiosis in an asymptomatic patient: marker of cardiovascular risk?].

PMID- 15151800
TI  - [The HIV test and osteonecrosis].

PMID- 15151799
TI  - [Diffuse abdominal pain: pneumoperitoneum].

PMID- 15151801
TI  - A report on myself: the science and/or art of assessment.
AB  - Disregarding my empirically documented warnings to generations of students, I am
      ultimately succumbing to my own eisegesis. In this article, I proffer a personal
      exemplar of low- and high-inference interpretation of significant persons,
      events, and products during my professional lifetime. These selected bits of data
      are contained in childhood and educational experiences, three chronological
      periods, three 1949 Thematic Apperception Test (Murray, 1943) stories, and bits
      of several poems. These data coalesce in an interpretive statement, analogous to
      an assessment report but ultimately something more and something less than an
      optimal report. As an interpretive schema, a hierarchal model of clinical
      inference illustrates and exemplifies employment of distinct levels to increase
      the reliability of high-inference interpretation. While inadequately equipped as
      a psychologist assessor for such self-scrutiny, this narrative may provide a case
      history exemplar of a process that has relevance for myself, for the Society of
      Personality Assessment, and for understanding personality within a human science
      aegis.

PMID- 15151802
TI  - Saul Rosenzweig's purview: from experimenter/experimentee complementarity to
      idiodynamics.
AB  - Following a brief personal biography, an exposition of Saul Rosenzweig's
      scientific contributions is presented. Starting in 1933 with
      experimenter/experimentee complementarity, this point of view was extended to
      implicit common factors in psychotherapy Rosenzweig (1936) then to the
      complementary pattern of the so-called schools of psychology Rosenzweig (1937).
      Similarly, converging approaches in personality theory emerged as another type of
      complementarity Rosenzweig (1944a). The three types of norms-nomothetic,
      demographic, and idiodynamic-within the range of dynamic human behavior were
      formulated and led to idiodynamics as a successor to personality theory. This
      formulation included the concept of the idioverse, defined as a self-creative and
      experiential population of events, which opened up a methodology
      (psychoarcheology) for reconstructing the creativity of outstanding scientific
      and artistic craftsmen like William James and Sigmund Freud, among psychologists,
      and Henry James, Herman Melville, and Nathaniel Hawthorne among writers of
      fiction.

PMID- 15151803
TI  - A comparison of the MCMI-III personality disorder and modifier indices with the
      MMPI-2 clinical and validity scales.
AB  - In this study, we examined the relationship of the MCMI-III (Millon, Davis, &
      Millon, 1997; Millon, Millon, & Davis, 1994) modifier indices and personality
      disorder scales to the validity and basic clinical scales of the MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). The MCMI-III modifier indices
      highly correlated with all of the MMPI-2 validity scales except for the F(p)
      scale. Similarly, the MCMI-III personality disorder scales strongly covaried with
      the MMPI-2 validity and clinical scales except for the F(p) and 5 (Mf) scales. A
      factor analysis with Promax rotation revealed substantial relationships between
      the MMPI-2 and MCMI-III. However, the MMPI-2 F(p) scale did not tend to correlate
      with MMPI-2 or MCMI-III scales, indicating that F(p) scale variance was largely
      independent of other scales. The results suggest that clinicians should consider
      the interrelationship between personality characteristics and dissimulation.

PMID- 15151805
TI  - Curiosity and exploration: facilitating positive subjective experiences and
      personal growth opportunities.
AB  - In an effort to expand research on curiosity, we elaborate on a theoretical model
      that informs research on the design of a new measure and the nomological network
      of curiosity. Curiosity was conceptualized as a positive emotional-motivational
      system associated with the recognition, pursuit, and self-regulation of novelty
      and challenge. Using 5 independent samples, we developed the Curiosity and
      Exploration Inventory (CEI) comprising 2 dimensions: exploration (appetitive
      strivings for novelty and challenge) and absorption (full engagement in specific
      activities). The CEI has good psychometric properties, is relatively unaffected
      by socially desirable responding, is relatively independent from positive affect,
      and has a nomological network consistent with our theoretical framework.
      Predicated on our personal growth facilitation model, we discuss the potential
      role of curiosity in advancing understanding of various psychological phenomena.

PMID- 15151804
TI  - On the dimensionality of the stress-related growth scale: one, three, or seven
      factors?
AB  - We examined the factorial validity and dimensionality of the Stress-Related
      Growth Scale (SRGS; Park, Cohen, & Murch, 1996) using a large multiethnic sample
      (n = 1,070). Exploratory and confirmatory factor analyses suggested that a
      multidimensional representation of the SRGS fit better than a unidimensional
      representation. Specifically, we cross-validated both a 3-factor model and a 7
      factor model using confirmatory factor analysis and were shown to be invariant
      across gender and ethnic groups. The 3-factor model was represented by global
      dimensions of growth that included rational/mature thinking, affective/emotional
      growth, and religious/spiritual growth. We replicated the 7-factor model of
      Armeli, Gunthert, and Cohen (2001) and it represented more specific components of
      growth such as Self-Understanding and Treatment of Others. However, some factors
      of the 7-factor model had questionable internal consistency and were strongly
      intercorrelated, suggesting redundancy. The findings support the notion that the
      factor structure of both the original 1-factor and revised 7-factor models are
      unstable and that the 3-factor model developed in this research has more reliable
      psychometric properties and structure.

PMID- 15151806
TI  - Alexithymia and psychopathy: comparison and application of California Q-set
      Prototypes.
AB  - Although alexithymia and psychopathy have long been linked, the relationship
      between the two constructs remains unclear. In this study, we used the California
      Q-set Alexithymia Prototype (CAQ-AP; Haviland & Reise, 1996) and Psychopathy
      Prototype (CAQ-PP; Reise & Oliver, 1994) to clarify the relationship between the
      two constructs and evaluate both in a sample of contemporary and historical
      political leaders (N = 42). Our data show that both individuals with prototypic
      alexithymia and psychopathy lack empathy and insight and are not introspective.
      The prototypic person with alexithymia, however, is anxious, overcontrolled,
      submissive, boring, ethically consistent, and socially conforming, whereas the
      prototypic individual with psychopathy is anxiety-free, undercontrolled,
      dominant, charming, deceitful, and nonconforming. Characteristics of both were
      relatively common among the 13 controversial and notorious leaders and relatively
      uncommon among the 29 generally respected leaders in the sample. The CAQ-AP and
      the CAQ-PP appear to be useful for evaluating alexithymic and psychopathic
      features in public figures.

PMID- 15151807
TI  - Defense mechanisms and self-reported violence toward partners and strangers.
AB  - We examined the relationship between defense mechanisms and self-reported
      violence toward partners and toward strangers in a sample of college student men.
      Fifty men completed the Thematic Apperception Test (TAT; Murray, 1943) and the
      Conflict Tactics Scale (CTS; Straus, 1979), a self-report measure of strategies
      (including violence) for resolving conflicts with partners and strangers. The TAT
      responses were coded for defense mechanisms with the Defense Mechanisms Manual
      (Cramer, 1991b). The relative use of identification was negatively correlated (r
      = -.49, p <.001), and the relative use of projection was positively correlated (r
      =.49, p <.001) with the most extreme CTS report of violence toward partners. The
      relative use of identification was negatively correlated with the most extreme
      CTS report of violence toward strangers (r = -.34, p <.05). The relative use of
      denial was positively correlated with the most extreme CTS report of violence
      toward strangers (r =.32, p <.05).

PMID- 15151808
TI  - Convergent and discriminant validity of three measures of depressive personality
      disorder.
AB  - Sixty-eight outpatients from a veterans' administration psychiatry clinic and
      community mental health center were assessed with 3 measures of depressive
      personality disorder (DPD)-the Diagnostic Interview for Depressive Personality
      Disorder (Gunderson, Phillips, Triebwasser, & Hirschfeld, 1994), the Depressive
      Personality Disorder Inventory (Huprich, Margrett, Barthelemy, & Fine, 1996), and
      the Structured Clinical Interview for DSM-IV Axis II Disorders (First, Gibbon,
      Spitzer, Williams, & Benjamin, 1997a)-to evaluate their convergent and
      discriminant validity. Evidence supporting the measures' validity was mixed. The
      rate of convergence of depressive personality diagnoses across 3 measures was
      less than optimal, but the degree of intercorrelation among the measures was
      strong. Although depressive personality scores had moderate levels of
      intercorrelations with other personality disorders, the degree of
      intercorrelation decreased substantially after controlling for depressive
      symptoms. I conclude that further work is needed to strengthen the validity of
      measures of DPD.

PMID- 15151812
TI  - Myosin light-chain kinase contributes to short-term endothelial cell cytoskeletal
      alteration induced by serum from burned rats.
AB  - OBJECTIVES: To investigate the time-dependent effects of serum from burned rats
      on cytoskeletal filamentous actin (F-actin) reorganization by visualizing their
      distribution in human umbilical vein endothelial cell line ECV-304 and evaluate
      the role of myosin light-chain kinase (MLCK) in this process. METHODS: The serum
      starved ECV-304 cells were incubated with the serum from burned rats for 30 min,
      1, 2, 4, and 6 h, respectively, and 30 min before or after the incubation, the
      cells were treated with 5 micromol/L ML-7 for 30 min. F-actin was stained with
      rhodamine-phalloidin and observed under fluorescence microscope. RESULTS: Under
      normal condition, F-actin was distributed mainly in the cortical area of the
      endothelial cells. After stimulation with the burn serum, stress fiber formation
      could be clearly seen in the endothelial cells, exhibiting a time-dependent
      enhancement in a time course ranging from 30 min to 6 h. Such an effect could be
      significantly inhibited by a 30-min pretreatment of the cells with MLCK-specific
      inhibitor ML-7. Inhibition of MLCK also reversed actin reorganization in the
      endothelial cells pretreated with the burn serum. CONCLUSION: Serum from burned
      rats induces characteristic morphological changes in the endothelial cell actin
      cytoskeleton mainly due to the MLCK activation, an effect that can be reversed by
      the inhibition of MLCK.

PMID- 15151813
TI  - Ligase chain reaction for Chlamydia trachomatis detection in urine specimens from
      symptomatic and asymptomatic men.
AB  - OBJECTIVE: To determine the sensitivity and specificity of ligase chain reaction
      (LCR) for detection of Chlamydia trachomatis (C. trachomatis) in the urine of
      symptomatic and asymptomatic men. METHODS: C. trachomatis was detected by LCR in
      both first-void urine (FVU) and urethral swab cultures from 852 randomly selected
      male outpatients seeking medical attention for sexually transmitted diseases. In
      cases with discrepancy between the results yielded by the two methods, a second
      LCR directed against a gene fragment encoding the major outer membrane protein
      was performed. The results were evaluated on the basis of an expanded gold
      standard. RESULTS: The sensitivity and specificity was 98.6% and 99.4% with LCR,
      respectively, and was 77.4% and 99.5% with urethral swab culture. The sensitivity
      of LCR was much higher than that of urethral swab culture P<0.001 . The presence
      or absence of urethral symptoms did not show any influence on the results.
      CONCLUSION: LCR is sensitive and specific for detecting C. trachomatis
      infections, and FVU can be used for non-invading diagnosis and screening of the
      infection in men.

PMID- 15151814
TI  - Thoraco-umbilical flap: experience with 33 cases.
AB  - From August, 1996 to June, 2000, 33 patients received transfer of free thoraco
      umbilical flaps for repair of various soft-tissue defects. The size of the flaps
      ranged from 10 to 40 cm in length and 8 to 25 cm in width, with blood supply of
      the flaps derived from the largest periumbilical perforating branch of the deep
      inferior epigastric vessels. The indications of this flap included complex
      extremity trauma or large skin loss resulted from soft tissue tumor resection,
      either acute or postprimary. The overall success rate was 100% in the 33 cases.
      The donor area was closed directly with 10- to 12-cm-wide flaps, leaving an
      inconspicuous scar, whereas larger flaps required skin grafting. A 2-year follow
      up found uneventful healing of all the flaps with minimal donor abdominal
      morbidity.

PMID- 15151815
TI  - [Early-stage hemodynamic changes in dogs with gunshot wound in seawater].
AB  - OBJECTIVE: To investigate the hemodynamic changes in the early stages of gunshot
      wound of dogs in seawater for exploring early treatment protocol. METHOD:
      Fourteen conventional Beagles models undergoing gunshot wound in seawater were
      used along with another 2 dogs receiving the wound on land to serve as control.
      After the dogs were rescued from the seawater, the respiration (R), heart rate
      (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean
      arterial pressure (MAP), central venous pressure (CVP), pulmonary arterial wedge
      pressure (PAWP), and cardiac output (CO) were measured continuously in the early
      stages of the wound (53.62+/-12.19 min following injury), followed by statistical
      analysis of the results. RESULTS: Compared with the control group, the
      hemodynamic disturbance of the dogs receiving the wound in seawater was
      relatively severe during the first 15 min of the wound. The mortality tended to
      descend relevant to the position of the wounds, in the order of the head, chest,
      abdomen and limbs. CONCLUSIONS: Gunshot wound in seawater may cause severe
      hemodynamic changes, resulting in progressive dysfunction of circulation and high
      mortality rate. Early treatment should be targeted at hemodynamic stabilization
      in accordance to the characteristic changes during the early stages of the wound.

PMID- 15151816
TI  - [Transfection of human umbilical vein endothelial cell line ECV-304 with liposome
      oligonucleotide complexes under hypothermic and anoxic conditions].
AB  - OBJECTIVE: To investigate the transfection efficiency of nuclear factor (NF)
      kappaB decoy oligodeoxynucleotides (ODN) mediated by in vivo liposome in human
      umbilical vascular endothelial cell line ECV-304 under hypothermic and anoxic
      conditions. METHODS: ECV-304 cells were cultured in RPMI 1640 culture medium
      containing 10% fetal bovine serum at 37 degrees Celsius; in the presence of 5%
      CO2. Liposome-ODN complexes were prepared just before use and added to the cells
      with a liposome-ODN charge ratio of 2:1. ECV-304 cell monolayers were transfected
      with liposome-ODN complexes containing 0.50, 0.75, 1.00 and 1.25 micromol/L ODN
      respectively in Euro-Collins solution (ECs) at 4 degrees celsius; and then stored
      for 2, 4, 6 and 8 hours respectively under anoxic condition. The ODN without
      liposome was transfected into ECV-304 cells under identical conditions as the
      control. The distribution of fluorescein isothiocyanate (FITC)-labeled ODN in ECV
      304 cells was observed by fluorescence microscope, and the transfection
      efficiency and mean fluorescence intensity (MFI) were evaluated by flow
      cytometry. RESULTS: MFI was enhanced as the storage time extended and ODN
      concentration increased, reaching the peak level at 6 h (P<0.05). After a 6-hour
      storage, most of the ODN was found to locate in the cell nuclei, and the
      transfection efficiency did not vary significantly between the groups. Compared
      with the control group, however, the differences in transfection efficiency and
      MFI were significant. CONCLUSION: ODN can be highly efficiently transfected into
      ECV-304 cells by in vivo liposome in ECs under hypothermic and anoxic conditions,
      which provides an experimental basis for further study of the donor organ
      preservation at the level of genetic regulation.

PMID- 15151818
TI  - [Effects of urotensin II on cultured cardiac fibroblast proliferation and
      collagen type I mRNA expression].
AB  - OBJECTIVE: To observe the effect of urotensin II on cultured cardiac fibroblast
      collagen type I mRNA expression and proliferation, thereby to explore the role of
      urotensin II in myocardial remodeling in the event of cardiac failure. METHODS:
      Cardiac fibroblasts of neonatal Sprague-Dawley rats isolated by trypsin digestion
      method were stimulated by urotensin II at varied concentrations when the cells
      reached growth arrest. MTT assay was employed to measure the proliferation and
      determine the number of the cells, and reverse transcriptional (RT)-PCR used to
      detect the collagen mRNA expression. RESULTS: With the increase of urotensin II
      concentration, the optical density at 570 nm of the fibroblasts as shown by MTT
      assay first increased but then decreased, and remained at a significantly higher
      level in the cells treated with 1x10(-8) or 1x10(-9) mol/L urotensin II as
      compared with the control (P<0.05). The collagen type I mRNA levels of the cells
      treated with 1x10(-7), 1x10(-8) or 1x10(-9) mol/L urotensin II were significantly
      higher than that of the control cells (P<0.01). CONCLUSION: Urotensin II can
      directly induce cardiac fibroblast proliferation and significantly increase
      collagen type I mRNA expression, suggesting the crucial role of urotensin II in
      myocardial remodeling.

PMID- 15151817
TI  - [Ultrastructural changes in muscular tissues of dystrophin/utrophin double
      knockout mice after bone marrow-derived mesenchymal stem cell transplantation].
AB  - OBJECTIVE: To observe the ultrastructural changes in the muscular tissues of
      Duchenne muscular dystrophy mouse models with dystrophin/utrophin double-knockout
      (DKO) after transplantation of bone marrow-derived mesenchymal stem cells (MSCs).
      METHODS: The fifth passage of in vitro cultured MSCs from SD rats were
      transplanted into the DKO mice via the tail vein, and the ultrastructural changes
      in the gastrocnemius of the recipient rats were observed using transmission
      electron microscope 15 weeks after the transplantation. RESULTS: The fifth
      passage of the in vitro cultured MSCs growing in colonies possessed good
      homogeneity with low immunogenic activity for transplantation via the tail vein.
      After transplantation, the DKO mice exhibited improved motor function and
      prolonged survival period. Ultrastructural observation of the gastrocnemius of
      the recipient DKO mice revealed much alleviated sarcolemmal disruption,
      dissociation and edema of the subsarcolemmal tissues, central nuclear shift,
      loosening of the local myofibrils, inflammatory cell infiltration and connective
      tissue hyperplasia in comparison with the tissues from the DKO mice without MSC
      transplantation. Fusion of several immature nuclei was observed in the
      subsarcolemmal region. CONCLUSIONS: MSCs possess strong plasticity in vitro and
      in vivo, and after transplantation, the MSCs may migrate to lesioned muscular
      tissues via the blood circulation to participate in the repair and regeneration
      the atrophied muscular tissues.

PMID- 15151819
TI  - [Cloning of differentially expressed genes of eosinophils from asthmatic patients
      by suppression subtractive hybridization].
AB  - OBJECTIVE: To explore the molecular mechanism of eosinophils for its role in
      bronchial asthma. METHODS: The total RNA extracted from the eosinophils of
      patients during the onset of asthma was used as the tester and the total RNA
      obtained after treatment served as the driver. cDNA suppression subtractive
      hybridization (SSH) was performed using the protocols described in the Clontech
      SMART PCR cDNA Syn thesis Kit and PCR-Select cDNA Subtraction Kit. The subtracted
      cDNA was then inserted into T vector to generate subtracted cDNA library. Clones
      of the subtracted cDNA library were screened by hybridization and the insert
      sequence of the positive clones was compared with the sequence in the GenBank.
      RESULTS: A total of 400 clones selected from the subtracted cDNA library were
      amplified by PCR and about 85% of these clones contained inserts. Six
      differential cDNA fragments were acquired after two differential screening. These
      genes were involved in the regulation of proinflammatory response, signal
      transduction, energy metabolism and cell apoptosis. CONCLUSION: Differentially
      expressed genes of the eosinophils during the onset and the remission stage of
      bronchial asthma can be effectively cloned by SSH, which provides a solid
      foundation for clarifying the molecular mechanism of eosinophils in asthma and a
      theoretical base for clinical treatment and prevention of asthma.

PMID- 15151820
TI  - [Exon polymorphism of human RHD gene].
AB  - OBJECTIVE: To study exon polymorphism of human RHD gene and investigate the
      genetic mechanism of RhD-negative individuals. METHODS: PCR using sequence
      specific primers (PCR-SSP) was performed on 40 RhD-positive, 120 RhD-negative and
      2 weak D blood samples. RESULTS: All 10 exons could be detected in the 40 RhD
      positive and 2 weak D samples. Out of the 120 RhD-negative samples, 28 (23.33%)
      carried 10 exons, 19 (15.83%) lost most of the 10 exons (with mainly intermediate
      deletion), and 73 (60.83%) had deletion of all the 10 exons; 19 samples of Del
      phenotype identified from the 120 RhD-negative samples had all the 10 exons.
      CONCLUSION: Polymorphism of the exon structure of RHD gene is present in RhD
      negative individuals, characterized chiefly by gross deletion, partial deletion
      and non-deletion.

PMID- 15151821
TI  - [Conditions for large-scale production of genetically engineered E.coli bearing
      humanized anti- HBsAg Fab].
AB  - OBJECTIVE: To define the conditions for large-scale production of genetically
      engineered E.coli bearing humanized anti-HBsAg Fab. METHOD: Characteristic growth
      and expression of the engineered E.coli were observed during fermentation in the
      shaking flask to define the optimal culture conditions to achieve the highest
      production levels. On the basis of the observation results, the E.coli was
      cultured in a fermentor using the fed-batch method to determine the optimal
      production techniques. RESULTS: Observation of the bacterium in the shaking flask
      showed initiation of the induction procedure in the mid-log growth phase at 25
      degrees Celsius; with 0.2% arabinose resulted in the highest production of anti
      HBsAg Fab. The D(600) value of the culture reached 55.2, equivalent to 110 g/L
      wet weight of the bacterium, using the DO-stat fed-batch method. The resultant
      Fab showed well-preserved biological activity. CONCLUSION: Reliable techniques
      for rapid and massive production of the Fab have been developed.

PMID- 15151822
TI  - [Antisense human telomerase reverse transcriptase inhibits leukemia cell
      proliferation in vitro].
AB  - OBJECTIVE: To study the inhibitory effect of antisense human telomerase reverse
      transcriptase (hTERT) on leukemia cell proliferation in vitro. METHODS: Sense and
      antisense hTERT eukaryotic expression vectors previously constructed were
      transfected into leukemia cell line HL(60) using SuperFect transfection reagent
      (Qiagen) to obtain HL(60)-s and HL(60)-as, and the G418-resistant colonies were
      identified for the presence of hTERT insert by PCR with T7 and pcDNA3.1/BGH
      reverse primers. Endogenous hTERT mRNA expression and telomerase activity were
      then detected by quantitative real-time RT-PCR and telomerase associated protein 
      silver staining in each cell line. MTT cellular proliferation assay, soft agar
      colony formation assay and flow cytometry were also employed to analyze the
      changes in proliferation capacity of leukemia cell in vitro and apoptosis of the
      tumor cells induced by antisense hTERT. RESULTS: Antisense hTERT remarkably
      reduced endogenous hTERT mRNA expression (P<0.01) and down-regulated telomerase
      activity in HL(60), as compared with the blank control and sense hTERT. After 25
      passages of the 3 cell lines, a 7-day cell growth curve and the numbers (size) of
      soft agar colony formation showed that the proliferation rates and the anchorage
      independent growth ability of HL(60)-as cells were significantly decreased in
      comparison with HL(60) and HL(60)-s cells, but a significant increase in
      apoptosis of HL(60)-as cells occurred as determined by flow cytometry.
      CONCLUSIONS: Antisense hTERT can obviously inhibit leukemia cell growth and
      proliferation in vitro, and this telomerase-targeted molecular biotherapy may be
      achieved by apoptosis pathway through down-regulation of hTERT mRNA and
      telomerase activity.

PMID- 15151823
TI  - [Application of microarrays in screening the tumor-specific genes in the genome
      of K562 cells].
AB  - OBJECTIVE: To screen tumor-specific genes of K562 cells using DNA microarray
      technique. METHODS: The genomic DNA of normal white blood cells and cultured K562
      cells were respectively purified and digested with Sau3A I, and the digested DNA
      fragments of K562 cells were cloned into TA cloning vector to construct the
      corresponding genomic DNA library. The insert genomic DNA fragments were
      amplified from the library to prepare the microarray using Cartesian 5500
      Microarrayer. The digested genomic DNA fragments of normal white blood cells were
      labeled with fluorescent Cy3 by restriction display PCR (RD-PCR), followed by
      hybridization with the microarray, after which the slide was washed and scanned
      with ScanArray. RESULTS: Among the 426 target genes, 42 differential genes were
      identified in the genomic DNA of K562 cells in comparison with the normal white
      blood cells. One of the genes was identified as the breakpoint cluster gene (BCR)
      after sequence analysis. CONCLUSIONS: The DNA microarrays we constructed may
      effectively identify the tumor-specific genes in K562 cells, and DNA microarray
      technique can be helpful in elucidating the molecular mechanisms of tumorigenesis
      at the genomic level.

PMID- 15151824
TI  - [Effects of anti-HPV16 E6-ribozyme on invasiveness of cervical carcinoma cell
      line CaSKi and vascular endothelial growth factor expression].
AB  - OBJECTIVE: To investigate the changes in the invasiveness of cervical cancer cell
      line CaSKi and the expression of vascular endothelial growth factor (VEGF) in
      response to treatment with anti-HPV16 E6-ribozyme, which plays a important role
      in the malignant phenotype and conversion of cervical cancer cells. METHODS: By
      means of lipofectin transfection, anti- HPV16 E6-ribozyme and empty eukaryotic
      expression plasmids were respectively transfected into CaSKi cell line
      (designated as CaSKi-R and CaSKi-P respectively). CaSKi, CaSKi-R and CaSKi-P
      cells were observed for their cell growth curves, clone forming ability on soft
      agar and tumorigenicity in nude mice. One-step reverse transcriptional PCR (RT
      PCR) was employed to examine the expression of VEGF. RESULTS: No significant
      differences were found in the growth rate, clone forming ability and
      tumorigenicity between CaSKi and CaSKi-P cells. In contrast, CaSKi-R exhibited
      obviously decreased growth rate, clone forming ability and tumorigenicity
      (P<0.05). RT-PCR analysis showed that the expression levels of VEGF mRNA in CaSKi
      R cells were lower than those in CaSKi-P and CaSKi cells. CONCLUSION: Anti-HPV16
      E6-ribozyme may reduce the proliferative ability and invasiveness of cervical
      cancer cell line CaSKi, possibly through decreasing VEGF expression in CaSKi
      cells.

PMID- 15151825
TI  - [Immunohistochemical study of in situ CD86 expression in rejected rat corneal
      graft after penetrating keratoplasty].
AB  - OBJECTIVE: To investigate the expression of CD86 co-stimulatory molecules in
      rejected rat corneal graft in situ after penetrating keratoplasty. METHODS: Rat
      models of orthotopical corneal transplantation were established, and after the
      occurrence of graft rejection, immunohistochemical staining was performed on the
      corneal whole-mounts and the spleen tissue of the recipient rats. RESULTS:
      CD86(+) cells were detected in the epithelium of the corneal graft during
      allograft rejection but not in normal cornea. CONCLUSION: In situ expression of
      costimulatory molecules in the corneal allograft may be related to the acute
      immune rejection after penetrating keratoplasty.

PMID- 15151826
TI  - [Ultrasound microbubbles promote thrombolysis of rabbit femoral artery thrombus].
AB  - OBJECTIVE: To evaluate the efficacy of intravenous ultrasound microbubbles for
      thrombolysis of arterial thrombus without using thrombolytic drugs. METHODS:
      Twelve rabbit models of acute bilateral femoral artery thrombosis were
      established and 6 of them received transcutaneous ultrasound and intravenous
      albumin microbubble treatment for thrombosis on one side while only microbubble
      treatment for the other side. The other 6 rabbits received ultrasound treatment
      on one side but no treatment on the other to serve as the control group. RESULTS:
      None of the 6 arteries treated with microbubbles alone and only 2 arteries
      treated with ultrasound alone in the 6 control rabbits were recanalized. All the
      6 femoral arteries treated with microbubbles together with ultrasound were
      recanalized (P=0.014), with significantly shorter patent time and smaller
      residual thrombus cross-sectional area than those of the arteries with only
      ultrasound treatment (P=0.004 and P=0.003, respectively). CONCLUSION: Treatment
      with intravenous microbubbles assisted by transcutaneous ultrasound effectively
      promotes arterial thrombolysis in vivo, and this technique can be of significance
      in clinical treatment of acute thrombotic occlusions.

PMID- 15151827
TI  - [Subconjunctival interleukin-1 receptor antagonist inhibits graft rejection
      following high-risk penetrating keratoplasty in rats].
AB  - OBJECTIVE: To observe the roles of subconjunctival administration of interleukin
      1 receptor antagonist (IL-1ra) promoting corneal graft survival in rat models of
      high-risk penetrating keratoplasty. METHODS: Corneal vascularization was induced
      in 40 Sprague-Dawley rats (40 eyes) by passing 10-0 silk suture through the
      corneal stroma, and 30 of these rats received corneal grafts from Wistar rats to
      establish high-risk keratoplasty models and were divided into 3 groups to receive
      their respective treatment with IL-1ra eye drops (50 microg/ml), 1% CsA eye
      drops, administered 3 times a day, or no treatment. All the rats were treated by
      Tobra Dex eye drops and Tropicamid eye drops, 3 times a day for 14 consecutive
      days after the operation. During the 30-day observation, the survival of the
      grafts was recorded, and all the grafts were evaluated for signs of rejection.
      RESULTS: The mean survival times (MST) of the grafts of the treatment groups with
      IL-1ra and CsA were 12.00+/-1.50 d and 10.44+/-1.13 d respectively, significantly
      longer than that in the untreated model group (8.00+/-1.25 d, t=0.00, P<0.01),
      and the difference in the MST between the 2 treatment groups was also significant
      (t=0.00, P<0.01). CONCLUSION: Treatment with IL-1ra may significantly prolong
      high-risk corneal allograft survival.

PMID- 15151828
TI  - [Dynamic changes in the expressions of myogenic regulatory factors MyoD and
      myogenin during repair of muscle injury].
AB  - OBJECTIVE: To observe the dynamic changes in the expressions of myogenic
      regulatory factors MyoD and myogenin during the repair of injured muscle.
      METHODS: Muscular injury model was established by local injection of bupivacain,
      and at different time points following the injection, the gastrocnemius muscles
      were collected for preparation of cryosections. HE staining was performed for
      examination of the pathological changes in the injured muscles, and the
      expressions of MyoD and myogenin were detected by SABC. RESULTS: MyoD-positive
      nuclei began to appear 18 h after muscle injury, reaching the peak till 48 h
      after the injury. Myogenin-positive nuclei appeared 24 h after muscle injury and
      peaked at 72 h. CONCLUSIONS: MyoD and myogenin play a role in muscle regeneration
      after muscle injury, and they may serve as the indexes to identify muscle
      precursor cells and mark muscle regeneration process.

PMID- 15151829
TI  - [Expression of human tissue-type plasminogen activator in cow mammary gland].
AB  - OBJECTIVE: To construct an expression vector for highly efficient expression of
      tissue-type plasminogen activator (t-PA) confined in the mammary gland of cow to
      develop a cow mammary gland bioreactor. METHODS: RT-Touch down-PCR was employed
      to amplify human tissue-type plasminogen activator (t-PA) cDNA, which was
      digested with the restriction enzymes and subsequently cloned into the vector
      pSP72 for constructing specific fusion gene only expressed in the mammary gland.
      The fusion gene was then transferred into the mouse zygote and the mammary gland
      tissue of mice and cows. RESULTS: t-PA was detected in the milks of mice and cows
      after the transgenic manipulation with microinjection and mammary gland injection
      of the fusion gene. CONCLUSIONS: The vector we constructed can effectively induce
      t-PA expression in the mammary gland, which is not influenced by different
      transgenic methods. The expression level of t-PA, however, is significantly
      higher in the milk of cows than in the milk of mice, suggesting the species
      specific difference in milk protein regulating system possibly is due to
      different factors and regulatory systems.

PMID- 15151830
TI  - [Effects of Shenshuai Yangzhen capsule on lipid metabolism disorder in rats with
      chronic renal failure].
AB  - OBJECTIVE: To investigate the therapeutic effect of Shenshuai Yangzhen capsule, a
      preparation of traditional Chinese medicine, on lipid metabolism disorder in rats
      with chronic renal failure (CRF) and explore its mechanism. METHODS: Fifty male
      SD rats received 5/6 nephrectomy for preparation of CRF models and were
      randomized into CRF group, gemfibrozil group, high-, moderate- and low-dose
      Shenshuai Yangzhen groups, and normal control group. After 4-week treatment as
      indicated, myocardial lipoprotein lipase messenger RNA (LPL mRNA) level were
      measured by RT-PCR in rats with surgically induced renal failure (two-stage
      subtotal nephrectomy). The blood lipid parameters in CRF rats were also
      determined. RESULTS: Compared with those in the CRF group, the plasma total
      cholesterol, triglyceride, low-density lipoprotein cholesterol and very-low
      density lipoprotein cholesterol concentrations in the treatment groups were
      significantly lower with substantially elevated plasma high-density lipoprotein
      cholesterol and LPL gene expression. No significant differences were noted
      between different dose groups of Shenshuai Yangzhen. CONCLUSION: Shenshuai
      Yangzhen capsule can regulate blood lipid levels in rats with renal insufficiency
      possibly by enhancing LPL gene expression.

PMID- 15151831
TI  - [Two-dimensional electrophoregram for proteomic analysis of rat brain with
      intrahippocampal amyloid beta injection and normal rat brain].
AB  - OBJECTIVE: To investigate the molecular mechanisms of Alzheimer's disease by
      comparing global protein patterns in two-dimensional electrophoregram (2-DE) of
      the brain of rats with intrahippocampal amyloid beta injection and normal rats.
      METHODS: From adult SD rats with intrahippocampal injection of amyloid beta, 200
      microg brain proteins were extracted with 9 mol/L urea, 4% CHAPS, 1% DTT, 0.5% CA
      and a cocktail of protease inhibitors. Immobilized pH gradient (IPG) isoelectric
      focusing electrophoresis of the extracted proteins was performed to obtain the
      electrophoretogram of the first dimension, with the second dimension obtained by
      vertical SDS-PAGE. The electrophoretograms were visualized using silver staining
      and analyzed with ImageMaster 2D-Elite software. RESULTS: On average, 496 and 491
      protein spots could be obtained in the electrophoregraphs for rats with amyloid
      beta and the control rats, respectively, and 30 of these spots exhibited
      quantitative changes. Another 11 and 6 spots were exclusively shown on the
      protein maps for amyloid beta-treated rats and control rats, respectively.
      CONCLUSION: The differentially displayed proteins in the brain identified between
      the rats with intrahippocampal amyloid beta injection and control rats may
      provide further insight into the pathogenesis of Alzheimer's disease and useful
      clues for developing new drugs for its treatment.

PMID- 15151832
TI  - [Microbial receptor competitive binding assay of basic macrolide antibiotics].
AB  - OBJECTIVE: To establish a biological method for determining the macrolide content
      in various matrices. METHODS Human serum, urine and tissue homogenate samples
      were diluted or extracted with MSU buffer, and the specimens of grain and
      premixed feed extracted with methanol-H(3)PO(4) buffer, before microbial receptor
      competitive binding assay was carried out on these various specimens, with the
      elimination of interference from methanol with the M8 buffer. RESULTS: The method
      was sensitive, class-specific and precise, and the recommended screening
      concentrations for specimens of the serum, urine, tissue and grains were 200,
      200, 100 and 1 200 ng/g (ng/ml), respectively, with a relative standard deviation
      less than 8%. CONCLUSION: Microbial receptor competitive binding assay is
      accurate and rapid for efficient qualitative and quantitative assay of the total
      macrolide content in various matrices.

PMID- 15151833
TI  - [Expression of telomerase reverse transcriptase and its significance in human
      fetal lung development].
AB  - OBJECTIVE: To investigate the expression and distribution of telomerase reverse
      transcriptase (hTERT) and its significance during the development of epithelial
      stem cells in human fatal lungs. METHODS: Human lung tissues were obtained at
      abortion from 37 fetuses 10-34 weeks of gestational age with parental consent,
      and the expression of hTERT in these tissues was examined by
      immunohistochemistry. RESULTS: In fetuses of 10 weeks old, hTERT was detected
      mainly in the epithelial cells of the proximal bronchi in the fetal lung, and
      migrated gradually to the distal bronchi as the lung developed. The hTERT
      expression level peaked at 17-20 weeks of gestation and then decreased over the
      period of alveolarization that occurred at about 25-26 weeks. In the later
      gestation period, strongly positive epithelial cells became concentrated in
      discrete patches near the basal membrane of the airway and scattered in only a
      few of the pulmonary alveoli. Morphologically, these cells resembled the basal
      cells and type II alveolar epithelial cells (AEC) or their progenitor cells.
      CONCLUSIONS: Telomerase expression and activity are hallmarks of the pulmonary
      stem or progenitor cells that maintain undifferentiated state and self-renewal
      capacity, and it plays a crucial role in the normal differentiation and
      regeneration of the bronchial and alveolar epithelial cells to maintain the
      epithelial integrity.

PMID- 15151834
TI  - [Association of basal ganglia damage with Chinese agraphia].
AB  - OBJECTIVE: To study the clinical features of Chinese agraphia caused by basal
      ganglia damage. METHODS: The Chinese speaking and writing abilities of 38
      patients with basal ganglia damage were evaluated with aphasia battery and
      agraphia battery of Chinese, respectively, and the agraphia quotient (AgQ) and
      the scores for writing abilities calculated. RESULTS: Of the 38 patients, 21 had
      left basal ganglia injury, which was responsible for aphasia in 18 and agraphia
      also in 18 patients. Another 14 patients had right basal ganglia injury and
      caused aphasia in 1 case and agraphia in 4. The rest 3 patients had injuries of
      the basal ganglia on both sides that resulted in aphasia in all and agraphia in 2
      of them. Significant difference was noted in the incidence of agraphia between
      patients with left and those with right basal ganglia injuries, characterized by
      difficulty in building the Chinese characters, mistakes in writing the characters
      and disability of writing at the level of sentences and paragraphs of Chinese.
      CONCLUSION: Basal ganglia damage may result in Chinese agraphia, due to,
      hypothetically, hypoperfusion, dysfunction of integration center, circuit damage
      and impaired function in extracting the graphical features of the Chinese
      characters from memory.

PMID- 15151835
TI  - [Clinical study of plasma urotensin II in patients with coronary heart disease].
AB  - OBJECTIVE: To investigate the changes in plasma urotensin II(U II) expression
      levels in patients with coronary heart disease (CHD). METHODS: Plasma U II levels
      in 50 CHD patients with coronary stenosis indicated by coronary angiography and
      20 healthy subjects were determined by radio immunoassay. RESULTS: Venous plasma
      U II levels were significantly lowered in CHD patients in comparison with the
      healthy subjects (1.61+/-1.02 pg/ml vs 3.70+/-1.30 pg/ml, P=0.000). In the CHD
      patient group, significantly differences were noted in the U II levels between
      patients with stable angina (2.62+/-1.20 pg/ml), unstable angina (1.39+/-0.80
      pg/ml) and acute myocardial infarction (AMI, 1.04+/-0.45 pg/ml, P=0.004). CHD
      patients with coronary artery occlusion and those with only coronary stenosis had
      comparable venous plasma U II levels (1.29+/-1.02 pg/ml vs 1.76+/-1.00 pg/ml,
      P=0.131), whereas the patients with restenosis after percutaneous transluminal
      coronary angioplasty (PTCA) had higher U II levels than the other subjects in the
      CHD patient group (2.28+/-0.94 pg/ml vs 1.40+/-0.96 pg/ml, P=0.008), and the
      femoral plasma U II levels were significantly elevated after PTCT, increasing
      from 1.18+/-1.14 pg/ml to a postoperative level of 2.22+/-1.77 pg/ml (P=0.001).
      CONCLUSION: U II might play a role in the pathophysiological process of CHD and
      can be involved in the restenosis after angioplasty.

PMID- 15151836
TI  - [Intestinal permeability of patients with advanced digestive tract malignant
      tumors].
AB  - OBJECTIVE: To assess the intestinal barrier function of patients with advanced
      digestive tract malignant tumors by measuring the changes in intestinal
      permeability. METHODS: Sixteen patients with digestive tract tumors and 16
      healthy volunteers were enrolled. After oral administration of mannitol and
      lactulose in deionized water, the 6-hour urine samples were collected for
      analyzing mannitol and lactulose concentrations using gas-liquid chromatography.
      RESULTS: Urine lactulose concentration and lactulose/mannitol (L/M) ratio of the
      tumor patients were increased in comparison with those of the healthy subjects
      (P<0.05). CONCLUSION: he intestinal permeability increased in these tumor
      patients, indicating intestinal barrier dysfunction.

PMID- 15151837
TI  - [Detection of serum coxsackievirus B-specific antibody and nucleic acid in aged
      patients with cardiopathy].
AB  - OBJECTIVE: To understand the status of coxsackievirus B (CVB) infection in senior
      subjects and explore the association of the infection with cardiovascular
      diseases. METHOD: By means of ELISA and RT-PCR, CVB IgG antibody and nucleic acid
      were detected in 172 patients with cardiopathy and 58 control subjects. RESULTS:
      The positivity rate of CVB IgG antibody was 43.61% (75/172) in the patient group
      and 15.52% (9/58) in the control group, showing obvious difference between the
      two groups. CVB RNA tests revealed a CVB RNA-positivity rate of 20.93% (36/172)
      in the former group and 3.45% (2/58) in the latter, with also a significant
      difference (P<0.01). CONCLUSION: CVB infection is prevalent in aged patients with
      heart disease, which should be given due attention to.

PMID- 15151838
TI  - [Short-term effect of treatment protocol utilizing levofloxacin, pasiniazide and
      M. Vaccae on multi- drug resistant pulmonary tuberculosis].
AB  - OBJECTIVE: To observe the effects of the protocol combining levofloxacin,
      pasiniazide, M. Vaccae (V+D+M protocol) in the treatment of multi-drug resistant
      pulmonary tuberculosis (MDR-TB). METHOD: Ninety-seven cases of MDR-TB randomized
      into V+D+M treatment protocol group (n=50) and control group (n=47) were observed
      for the negative sputum conversion rate, focal absorption, pulmonary cavity
      closure and improvement of immune function, after a 6-month treatment course.
      RESULTS: After the completion of the treatment course, the negative sputum
      conversion rate in V+D+M treatment protocol group was 84%, significantly higher
      than that in the control group (42%); the former group showed a focal absorption
      rate and pulmonary cavity closure rate of 83% and 66%, which were 33% and 26%
      respectively in the latter. In V+D+M treatment protocol group, T lymphocyte
      subgroups CD(3) and CD(4) were significantly elevated while CD(8) decreased after
      treatment, resulting in increased CD(4) to CD(8) ratio. The incidence of adverse
      effects resulting from the different treatment protocols in the two groups were
      comparable (30% vs 38%). CONCLUSION: V+D+M treatment protocol is effective for
      MDR-TB, which possesses the potential for application in clinical practice.

PMID- 15151839
TI  - [Detection of high-sensitivity C-reactive protein and total cholesterol/high
      density lipoprotein cholesterol ratio for diagnosis of coronary artery disease].
AB  - OBJECTIVE: To study the value of detecting high-sensitivity C-reactive protein
      (hs-CRP) combined with determination of total cholesterol/high-density
      lipoprotein cholesterol (TC/HDL-C) in the diagnosis of coronary artery disease
      (CHD). METHODS: A total of 240 patients with documented CHD and 40 healthy
      subjects were enrolled in this study for measurement of serum concentrations of
      hs-CRP, TC and HDL-C. RESULTS: The concentration of hs-CRP and TC/HDL-C ratio was
      significantly higher in CHD patients than in the control subjects (P<0.01). The
      positivity rate by detecting both the two markers (0.950) was higher than that of
      single marker detection of either hs-CRP (0.850) or TC/HDL-C (vs 0.767).
      CONCLUSION: Detection of hs-CRP combined with determination of TC/HDL-C may
      facilitate early diagnosis of CHD.

PMID- 15151840
TI  - [Automatic feature extraction and new method for retrieval from CT image
      database].
AB  - OBJECTIVE: To propose a new method for content-based retrieval from medical CT
      image database on the basis of automatically extracted features of the images.
      METHODS: An automatic feature extraction method is proposed based on expectation
      maximization algorithm. A CT image is represented by a set of regions, each of
      which is characterized by a fuzzy regional feature vector reflecting the grey
      level, texture, shape, and the cumulative distribution histogram feature of the
      region of interest (ROI) to efficiently describe the difference between the ROIs.
      RESULTS: Compared with the submitted query image, the target images were
      retrieved in the order of similarity calculated by the proposed similarity
      measures. CONCLUSION: The proposed technique for CT image retrieval is suitable
      for clinical application, with greater precision and efficiency for retrieval
      than the conventional methods.

PMID- 15151841
TI  - [Clinical observation of electrocardiographic changes in response to taxotere
      combined with adriamycin treatment for breast cancer].
AB  - OBJECTIVE: To study the effects of taxotere and adriamycin based chemotherapy on
      the electrocardiogram (ECG) of patients with locally advanced or metastatic
      breast cancer. METHODS: Chemotherapy combining taxotere (75 mg/m(2)) and
      adriamycin (5 mg/m(2)) once every 3 weeks was performed in 250 patients with
      locally advanced or metastatic breast cancer. Electrocardiograph was recorded
      before and after each treatment course for a total of 10 courses. RESULTS: After
      the completion of the 10 treatment courses, 8 (3.2%) patients had accelerated
      heart rate, 12 presented low voltage of QRS complex in the limb leads, and Q-T
      interval extension, ST segment depression, T-wave flattening, T-wave inversion
      occurred in 28, 18, 29, and 12 patients, respectively. The rest patients had no
      ECG changes. CONCLUSIONS: Taxotere and adriamycin as antitumor chemotherapeutic
      drugs may cause toxicity in the heart, and result in pericardial effusion,
      myocardial injury, chronic myocardial ischemia or hypoxia that may lead to
      abnormal changes in QRS complex and ST-T segment in ECG.

PMID- 15151842
TI  - [Induced differentiation of human peripheral blood CD68+ mononuclear cells into
      osteoclasts in vitro].
AB  - OBJECTIVE: To establish a method for obtaining highly purified primary human
      osteoclast precursors for the biochemical and molecular biological research.
      METHODS: CD68(+) mono/macrophages were separated from peripheral blood
      mononuclear cells (PBMCs) of healthy donors by means of immunomagnetic cell
      sorting for subsequent analysis with flow cytometry. The isolated cells were
      incubated on coverslips or bone slices in the presence of dexamethasone(10(-8)
      mol/L), macrophage colony-stimulating factor (25 microg/L ) and soluble receptor
      activator of nuclear factor (NF)-kappaB ligand (s-RANKL, 16 microg/L). Calcitonin
      receptor (CR) immunocytochemistry and tartrate-resistant acid phosphatase (TRAP)
      histochemistry were employed. The bone slices were also studied by scanning
      electron microscopy (SEM). RESULTS: Fluorescence-activated cytometric analysis
      showed that 93.06%+/-0.61%  n=4  of the selected cells were CD68(+) cells. After
      7 days of culture of the CD68(+) cells, VR+, TRAP+ multinucleated giant cells
      appeared, and resorption lacunae could be observed by SEM. CONCLUSION: Highly
      purified CD68(+) cells can be obtained from human PBMCs as the osteoclast
      precursors, and mature osteoclasts can be induced from CD68(+) mono/macrophages
      by RANKL.

PMID- 15151844
TI  - [Iodine-131 therapy for large goiter with hyperthyroidism: clinical observation
      of 38 cases].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy and safety of iodine-131 therapy
      for large goiter complicated by hyperthyroidism. METHODS: After the diagnosis of
      large goiter complicated by hyperthyroidism was established, the weight of the
      patient's thyroid gland was determined, and the doses of iodine-131 calculated
      according to the formula currently available. After a single dose of oral iodine
      131 capsule, the patients were observed for the therapeutic efficacy and side
      effects. Some patients were given the second or even the third dose of iodine
      131. RESULTS: All of the 38 patients were cured by 1 to 3 single doses of iodine
      131 therapy, of whom 23 (60.5%) needed only a single dose for the cure, 13
      (34.2%) required the second dose, and 2 (5.3%) necessitate a third dose.
      Hypothyroidism occurred in 4 cases (10.5%), and none of the patients developed
      hyperthyroidism crisis and dyspnea. CONCLUSIONS: Iodine-131 therapy for serious
      goiter with hyperthyroidism is safe and effective, which can be used as a routine
      therapy for this condition.

PMID- 15151843
TI  - [Diagnostic value of laparoscopy for pelvic masses in perimenopausal and
      postmenopausal women].
AB  - OBJECTIVE: To evaluate the value of laparoscopy in the diagnosis of pelvic masses
      in perimenopausal and postmenopausal women. METHODS: The results of laparoscopic
      examination performed in 117 perimenopausal and postmenopausal women with pelvic
      masses were retrospectively analyzed. RESULTS: Malignant tumors in 19 cases
      (16.2%) and benign tumors were identified in 98 cases, and all of them managed
      laparoscopically. CONCLUSION: Laparoscopy is safe and accurate in diagnosing
      pelvic masses in perimenopausal and postmenopausal women, and may help define the
      quality of the masse and provides means for early detection and treatment of
      malignant tumors.

PMID- 15151845
TI  - [Short-term effect of percutaneous transluminal coronary angioplasty with stent
      implantation in treating myocardial infarction with severe pump failure].
AB  - OBJECTIVE: To evaluate the short-term therapeutic effect of percutaneous
      transluminal coronary angioplasty (PTCA) with stent implantation in the treatment
      of myocardial infarction with severe pump failure. METHODS: The clinical data of
      73 patients receiving PTCA and stent implantation for myocardial infarction with
      severity pump failure were analyzed and grouped according the occurrence of
      complications, degree of the vascular lesions and the complexity of the surgical
      procedures. Preoperative and postoperative ventricular ejection fractions (LVEF)
      were compared in each case. RESULTS: The degree of vascular lesions and surgical
      complexity were not shown to relate to the occurrence of the complications.
      Except in cases complicated by chronic renal dysfunction, significant improvement
      was achieved in the patients 7 d after the operation (P<0.05), regardless of
      different degrees of vascular lesions and surgical complexity. CONCLUSION: PTCA
      with stent implantation is effective to improve the short-term cardiac function
      of patients with myocardial infarction and severe pump failure.

PMID- 15151846
TI  - [Management of extensive burn accompanying severe inhalation injury].
AB  - OBJECTIVE: To review our clinical experiences in the treatment of extensive burn
      accompanied by severe inhalation injury. METHODS: A retrospective analysis was
      conducted of 18 such cases admitted from 2000 to 2003 in light of the curative
      rate, mortality rate and measures for effective management. RESULTS AND
      CONCLUSIONS: Fifteen patients (83.3%) were cured and 3 (16.7%) died. The curative
      rate of extensive burn accompanied by severe inhalation injury can be enhanced by
      combining various treatments, including early preventive tracheostomy,
      appropriate tracheobronchial lavage, humidification and application of ambroxol;
      protective lung ventilation, and administration of growth hormones should be done
      as early as possible.

PMID- 15151847
TI  - [Dowel and composite resin as the post-core of long ceramic bridge for repair of
      dentition defect].
AB  - OBJECTIVE: To explore a new method for repairing the dentition defect involving
      multiple teeth. METHODS: Forty patients who had severe dentition defect were
      enrolled in this study. The defects were repaired by reserving the residual roots
      and the application of dowels and light-cure composite resin as the post-core of
      the long ceramic bridge. RESULTS: The patients were followed up for 2-4 years,
      and a success rate of 92.5% was achieved. CONCLUSION: Reserving the residual
      root, application of dowel and light-cure composite resin as the post-core of
      long ceramic bridge is effective for repairing severe dentition defect.

PMID- 15151848
TI  - [Application of echocardiographic monitoring in percutaneous cardiopulmonary
      support for the treatment of acute fulminant myocarditis: report of one case].
AB  - OBJECTIVE: To observe dynamic echocardiographic changes in patients with acute
      fulminant myocarditis and assess the clinical value of echocardiography in
      treatment with percutaneous cardiopulmonary support (PCPS). METHOD PCPS through
      the femoral artery/vein was used in the treatment of a patient with acute
      fulminant myocarditis, with dynamic echocardiographic observation of the atrial
      and ventricular volumes, left ventricular wall thickness, pulsatile amplitude and
      cardiac functions before and after PCPS. The position of the catheter of PCPS was
      also under dynamic bedside monitoring. RESULTS AND CONCLUSION The patient showed
      significant echocardiographic changes, such as weakening of the wall movement,
      lowered ejection fraction, widening of the left ventricular internal diameter
      with mild pericardial exudation. After PCPS, the cardiac functions such as the
      heart movement, ejection fraction and the shortening rate of the short axis were
      greatly improved as observed with ambulatory echocardiography. This case suggests
      that ambulatory echocardiography can be instrumental in the management of cardiac
      emergencies.

PMID- 15151849
TI  - [Clinical analysis of missed diagnosis of duodenal injury in 9 cases].
AB  - OBJECTIVE: To study the reasons and possibly solutions for missed diagnosis of
      duodenal injury. METHOD The clinical records were retrospectively analyzed in 9
      cases of missed diagnosis of duodenal injury treated in our hospital in the year
      1992 to 2002. RESULTS Of the 15 cases of duodenal injury, missed diagnoses
      occurred in 9 cases. The reasons for the missed diagnoses included complications
      by injuries of the other abdominal organs that concealed duodenal injuries,
      neglect of the light injuries, and the lack of clinical experience on the part of
      the young doctors. CONCLUSION Duodenal injury frequently occurs along with other
      abdominal organ injuries and is easy to escape detection, which can be avoided by
      careful preoperative examination of the characteristics of injuries and the
      patients' clinical manifestations after the injury.

PMID- 15151850
TI  - [Research and realization of web-based enterprise management].
AB  - Web-based enterprise management (WBEM) represents the major direction of current
      researches. In this paper, we elaborate on the norms and standards pertaining to
      WBEM and the major technical principles of its implement.

PMID- 15151851
TI  - The timing of natural prehension movements.
AB  - Prehension movements were studied by film in 7 adult subjects. Transportation of
      the hand to the target-object location had features very similar to any aiming
      arm movement, that is, it involved a fast-velocity initial phase and a low
      velocity final phase. The peak velocity of the movement was highly correlated
      with its amplitude, although total movement duration tended to remain invariant
      when target distance was changed. The low-velocity phase consistently began after
      about 75% of movement time had elapsed. This ration was maintained for different
      movement amplitudes. Formation of the finger grip occurred during hand
      transportation. Fingers were first stretched and then began to close in
      anticipation to contact with the object. The onset of the closure phase was
      highly correlated to the beginning of the low velocity phase of transportation.
      This pattern for both transportation and finger grip formation was maintained in
      conditions whether visual feedback from the moving limb was present or not.
      Implications of these findings for the central programming of multisegmental
      movements are discussed.

PMID- 15151852
TI  - Electromyographic evidence of neurological controller signals with viscous load.
AB  - Ensemble averaging after pre-editing of surface EMG potentials has enabled
      construction of underlying controller signals from stereotyped head movements.
      Carefully controlled, intended time-optimal movements by trained, actively
      participating human subjects have been found to yield repeatable, multi-pulse
      controller signals. Also, adaptive changes in these horizontal head movements in
      response to added viscous loads showed further causal relationships between
      movement dynamics and EMG signals from left and right splenius muscles. These
      experimental results are a base from which modeling studies can be performed to
      explicate the neurological control strategies used in the performance of this
      class of movements.

PMID- 15151853
TI  - The acquisiton of time properties associated with a sequential motor skill.
AB  - Three experiments are reported that examined the relative importance of phasing
      and duration training in the motor learning of a sequential task. In all three
      experiments, the task involved knocking down three barriers in a specified order.
      The Phasing task required the subject to contact each of the barriers in a
      particular goal time interval, that is, each segment had a particular movement
      time goal. The Duration task required the subject to contact the final barrier in
      a total elapsed-time goal defined by the experimenter. Following training, half
      of the subjects in each training condition transferred to either a novel Duration
      or a novel Phasing task. Phasing-trained subjects, compared to Duration-trained
      subjects, produced equivalent transfer performance on the Duration transfer task
      but superior performance on the Phasing transfer task. These results suggest that
      phasing serves as a higher-order source of information for the performer in a
      sequential motor task. in addition, these experiments complement and extend
      previous work by Shapiro (1977) and Summers (1975) which demonstrated that
      learned phasing patterns were not modified despite changes in the overall rate of
      performing a motor sequence. Our experiments indicate that phasing training
      increases the performer's sensitivity to phasing patterns such that novel
      temporal patterns can be produced when they are well-defined.

PMID- 15151854
TI  - Motor programming: does the choice of the limb which is to carry out the response
      imply a delay?
AB  - In many activities, the human being must quickly decide on the response to be
      produced following a change in the environment. In some of these situations, the
      limb that the individual chooses to carry out a response seems to be a
      significant element in performance. Thus, if the individual carries out the
      response with the limb closest to the target, the performance can improve because
      it will take less time to achieve the goal. However, it seems that in these
      situations, the human being does not take this decrease in movement time into
      consideration and that the response is carried out with the dominant hand. Why is
      this so? It may be because the reaction is faster when there doesn't have to be a
      choice as to which limb will carry out the response. The goal of this study was
      to check this possibility. In order to do so, the subjects performed a two choice
      reaction-time task. For this task, some subjects knew beforehand which hand they
      had to use to carry out the response while other subjects were unaware of this
      fact. The results of two experiments indicated that the choice of the limb which
      is to carry out the response requires no particular delay when the movement to be
      produced is externally guided.

PMID- 15151855
TI  - A note on stability in force applied to control a repetitive task with the legs.
AB  - The forces applied to pedals during cycling were collected every 40 ms from
      approximately 29,000 movement repetitions. Intra-cycle mean values of force and
      its variability were significantly correlated, supporting Schmidt's impulse
      variability theory of within-movement activities of the legs. In addition, as
      mean forces approached peak values, coefficients of variation decreased. From
      averages taken minute by minute, intra-cycle forces were seen to rise or fall in
      concert, implying that the pattern as a whole constituted a significant neuro
      muscular unit of control.

PMID- 15151856
TI  - Forgotten moments: a note on skewness and kurtosis as influential factors in
      inferences extrapolated from response distributions.
AB  - It is proposed that reliance on only the mean and standard deviation of a
      distribution to describe response frequency may lead to erroneous inferences
      concerning such distributions when skewness and kurtosis are present. After
      defining the first four moments of a distribution, it is demonstrated
      analytically that skewness and kurtosis may vary to systematically influence the
      mean and standard deviation of a set of related distributions. The significance
      of these relationships for the interpretation of differing response distributions
      is advanced through examples gleaned from the movement control literature. in
      addition, it is suggested that the use of bandwidths to select scores from a
      distribution for subsequent data analysis can further compound the problems of
      both descriptive and explanatory inference, particularly when skewness and
      kurtosis are features of such distribution(s). Whether or not inferential
      statistics are invoked, a veridical perspective of distributions is essential to
      meaningful data analysis.

PMID- 15151857
TI  - Notes on measurement of the magnitude of the asymmetrical tonic neck reflex
      response in normal preschool children.
AB  - This study investigated the magnitude of the asymmetrical tonic neck reflex
      (ATNR) response in forty preschool children, grouped by age (3 years and 5 years)
      and sex. The ATNR response was measured by electrogoniometers at the head and
      elbows and recorded graphically on an X-Y plotter. Change scores indicating the
      difference in degrees of elbow flexion before and after head rotation were
      analyzed. Repetition of the stimulus (head turning) to the left and to the right
      occurred under two test postures (supine, quadrupedal) with the effect of a
      blindfold nested within quadruped trials and the effect of added tension nested
      within supine, totaling 16 trials per child. The magnitude of the ATNR decreased
      significantly with age, but sex differences were not significant. The quadrupedal
      test posture produced significant increases in the supine posture. The blindfold
      did not produce significant main effects. Electrogoniometric measurement
      consistently demonstrated the magnitude of the ATNR in normal preschool children,
      which decreases with age, is dependent upon test posture and can provide
      numerical guides in clinical tests of central nervous system integration.

PMID- 15151858
TI  - Modification of muscle activation patterns during fast goal-directed arm
      movements.
AB  - The motor programming of fast goal-directed arm movements was studied in a
      tracking task. A target jumped once or twice randomly to the left or right
      direction with an interstimulus interval (ISI) in a range between 50 and 125
      msec. Double step stimuli were either two steps in the same direction (C-trial)
      or in opposite direction (R-trial). Tracking results show that at the beginning
      average EMG-activity is the same for responses to single step trials, R-trials
      and C-trials. Differences set in after some time equal to or somewhat shorter
      than ISI. It was concluded that muscle activation patterns of fast goal-directed
      movements are not preprogrammed but that they can be modified during the
      movement. The time interval between second target step and the moment when EMG
      activity of the double step response deviates from the EMG activity of a single
      step (RT2) could be smaller than the time interval between first target
      displacement and EMG onset. (RT1). If modification of the muscle activation
      pattern required a longer or larger activation of the active muscle, RT2 tended
      to be smaller than RT1, whereas RT2 was about equal to RT1 if the new muscle
      activation required a termination of the ongoing muscle activation pattern and
      the activation of another muscle.

PMID- 15151859
TI  - The micro-structure of tapping movements in children.
AB  - In order to investigate the development of movement speed in relation to movement
      organization, children of 5, 6, 7, 8 and 9 years of age and adults carried out a
      reciprocal tapping task, in which time pressure and distance were manipulated.
      The duration, velocity, acceleration and accuracy of the movements were compared
      between age groups. Age differences appeared mainly in the homing time, not in
      the duration of the distance covering movement phase. Accuracy and velocity of
      the distance covering movement phase differed with age. Time pressure affected
      the homing time, but not the duration of the distance covering phase. Distance
      manipulation affected mainly the velocity and duration of the distance covering
      movement phase and the homing time. In the discussion it is contended that age
      differences in homing time may be related to both the accuracy of the distance
      covering movement phase and the rate of information processing of the subject.

PMID- 15151860
TI  - The schematic representation of effector function underlying perceptual-motor
      skill.
AB  - Conceptual and methodological problems related to Schmidt' (1975) motor schema
      theory are discussed. In particular, the motor schema is interpreted as
      representing the dynamics of the system being controlled, which may or may not be
      associated with a referent movement pattern. Furthermore, it is suggested that
      prior familiarity with a control system's dynamics is a critical but uncontrolled
      factor in tests of the theory, and largely accounts for their equivocal findings.
      These ideas are examined by two experiments in which subjects had to bimanually
      control the movement of a computer-displayed cursor along a track on a CRT
      screen. Different track orientations required different patterns of movement not
      entailing a single generalized motor program. Experiment 1 shows that variable
      track performance with a given control system, results in better transfer to
      novel tracks than does fixed practice. Experiment 2 demonstrates that altering
      the control system disrupts performance whether or not the required movements
      remain the same. These results indicate the need for a fundamental modification
      of schema theory, such that a schematic representation of effector-environment
      relations (effector function) is available independently of particular movement
      patterns used in its acquisition.

PMID- 15151861
TI  - Incidental psychomotor learning: the effects of number of movements, practice,
      and rehearsal.
AB  - Three experiments were conducted to investigate the effects of the number of
      movements, practice, and rehearsal on incidental and intentional psychomotor
      learning. incidental learners received no formal instructions to learn the
      central task to which they were exposed in a choice reaction-time task. The
      movements to the targets in this task comprised a movement sequence. Intentional
      learners also performed the choice reaction-time task but were additionally
      instructed to remember the order of the movements. Intentional learning was
      superior to incidental learning, unless rehearsal was disrupted; all three
      independent variables demonstrated similar functional effects under both learning
      conditions. It was concluded that incidental and intentional learning are not
      distinct types of learning; and that "intent to learn" per se is a significant
      factor in psychomotor learning only when it elicits beneficial cognitive
      processes such as rehearsal.

PMID- 15151862
TI  - An empirical note on attaining a spatial target after distorting the initial
      conditions of movement via muscle vibration.
AB  - Can one's limb be accurately positioned to a spatial location without a veridical
      estimate of the initial conditions of movement? The experiment reported here
      examined this question by distorting perception of a limb's starting position via
      muscle vibration. Subjects executed rapid flexion movements under no-vibration,
      contralateral arm vibration, and ipsilateral arm vibration conditions. Vibration
      was applied to the biceps for 10 sec prior to the start of a reproduction
      movement. The results showed that vibration on the ipsilateral arm caused a
      significant increase in reproduction error, relative to the no-vibration and
      contralateral-vibration conditions. This finding provides additional evidence
      that accurate knowledge about the initial conditions of movement is a necessary
      component in positioning a limb.

PMID- 15151863
TI  - A note on constant error shifts in post-perturbation responses.
AB  - Response biasing was examined in the production of well-learned discrete timing
      responses. Interpolated movements consisted of trials which were briefly
      perturbed by an accelerating or decelerating force with subjects requested to
      amend the response in order to complete the trial successfully. Movement time
      analysis indicated that the response immediately following the perturbation trial
      demonstrated large biasing effects with the direction of the constant error shift
      a function of the direction of the perturbation. Responses following deceleration
      perturbations were produced too rapidly and those following acceleration
      perturbations were produced too slowly. Analysis of kinematic variables
      associated with these responses showed that post perturbation trials were
      characterized by systematic changes in peak acceleration and peak deceleration as
      well as the timing of these parameters. The biasing effects were temporary and
      showed other similarities to findings from short-term motor memory
      investigations. A number of differences were also noted along with methodological
      considerations for perturbation paradigms.

PMID- 15151864
TI  - Biomechanical motor patterns in normal walking.
AB  - Motor patterns in normal human gait are evident in several biomechanical and EMG
      analyses over the stride period. Some of these patterns are invariant over the
      stride period with changes of cadence, whole others are closely correlated with
      speed changes. The findings for slow, natural, and fast walking are summarized:
      1. Joint angle patterns over the stride period are quite invariant, and do not
      change with cadence; 2. Moment of force patterns at the ankle are least variable
      and quite consistent at all speeds; 3. A recently defined support moment is quite
      consistent at all speeds. 4. Moments at the knee and hip are highly variable at
      all cadences but decrease their variability as cadence increases; 5. Mechanical
      power patterns at all joints show consistent timing over the stride period; 6.
      EMG profiles of 5 muscles show consistent timing over the stride, but the
      amplitude increases as walking speed increases. Arguments are presented to
      support the concept that walking speed is largely controlled by gain and that the
      timing of the motor patterns, which is extremely tightly synchronized with the
      anatomical position, is under major afferent control.

PMID- 15151865
TI  - The lateral coding of rotations: a study of the simon effect with wheel-rotation
      responses.
AB  - A number of experimental studies have consistently shown the locus of spatial S-R
      compatibility effects to be the selection of the response within an abstract
      memory code. The purpose of the present study was to test, in the particular case
      of wheel rotations, the general proposition that any response that a subject
      internally codes in terms of left and right may be interfered with by the lateral
      location of the stimuli in a Simon paradigm. Experiment 1 showed that the
      auditory Simon effect occurred in a task where the subjects had to rotate a
      steering wheel bimanually either clockwise or counterclockwise according to sound
      pitch, despite the fact that responses of this kind are undefined with respect to
      laterality. Experiment 2 confirmed this result in a unimanual rotation condition
      and suggested that the ear-rotation compatibility effect may be added to the
      effect of a biomechanical factor, pronation versus supination, supporting the
      idea of an abstraction motor code. In Experiment 3, subjects rotated the steering
      wheel with their hands on the lowest part of the wheel. When the response
      movement made the spot of a C.R.T. move laterally in accordance with the
      performed rotation, the subjects coded their response directly in terms of its
      effect on the visual display. For subjects not receiving visual feedback, no
      compatibility effect occurred. however, the individual data were compatible with
      the notion that some subjects in this group coded their responses in terms of
      wheel rotations, and others in terms of hand movements.

PMID- 15151866
TI  - Memory for movement in blind children: the role of previous visual experience.
AB  - The role of previous visual experience in the reproduction of a criterion
      movement was examined in sighted, late-blinded, and congenitally blind children.
      Results showed that the congenitally blind reproduce movements at a low level of
      accuracy compared with the other two groups. Detailed analysis showed that
      although the congenitally blind could reproduce the extent of the movement
      accurately, the movement was poorly reproduced in terms of its orientation to the
      criterion movement and its orientation from a reference point. The role of prior
      vision in establishing a frame of reference is discussed.

PMID- 15151867
TI  - The organization of spontaneous leg movements in newborn infants.
AB  - Spontaneous, supine kicking in newborn (2- and 4-week-old) infants is described
      in terms of its temporal structure, interjoint coordination, and muscle
      activation characteristics as measured by surface electromyography. Phasic kick
      movements shoed a constrained temporal organization in the movement, but not the
      pause phases. Hip, knee, and ankle joints moved in temporal and spatial
      synchrony, and all three joints showed a rhythmical or periodic organization over
      time. EMGs revealed antagonist coactivation at the initiation of the flexor
      movement, but little or not extensor activity. The dorsal muscles, the
      gastrocnemius and hamstrings, showed less activity than the ventral pair,
      tibialis anterior and quadriceps. Burst and onset-to-peak durations were also
      constrained. As a result of neural mechanisms and biomechanical forces, newborn
      leg movements are structured muscle synergies. This organization has implications
      both for newborn functioning and for later development.

PMID- 15151868
TI  - Comment on the paper "Preprogramming, programming, and reprogramming of aimed
      hand movements as a function of age" by D.D. Larish and G.E. Stelmach (1982).

PMID- 15151869
TI  - An empirical note on the role of verbal labels in motor short-term memory tasks.
AB  - Previous studies of motor short-term memory have shown that when a criterion
      movement on a semicircular positioning task is accompanied by an appropriate
      verbal label (a clock-face position), recall of the movement is more accurate
      than when only the movement is presented. This increased accuracy could be due to
      either the additional spatial information provided by the label or enhanced
      retention of the movement information. These two alternatives cannot be
      distinguished on the basis of previous studies because the studies have not
      evaluated movement accuracy following presentation of the label alone. The
      present study employed such a condition in addition to the movement-only and
      movement-plus-label conditions to distinguish between the two hypotheses. In all
      conditions, subjects were asked to move to the criterion position after a
      retention interval of either 5 sec or 60 sec. Evidence indicated that subjects
      who received both the label and the movement tended to use the spatial
      information provided by the label at the 60-sec interval. The evidence did not
      indicate that the verbal label actually enhanced retention of the movement
      information.

PMID- 15151871
TI  - Rapid visual feedback processing in single-aiming movements.
AB  - A major line of behavioral support for motor-program theory derives from evidence
      indicating that feedback does not influence the execution and control of limited
      duration movements. Since feedback cannot be utilized, the motor-program is
      assumed to act as the controlling agent. in a classic study, Keele and Posner
      observed that visual feedback had no effect on the accuracy of 190-msec single
      aiming movements. Therefore visual feedback processing time is greater than 190
      msec, and, more importantly, limited duration movements are governed by motor
      programs. In the present paper, we observed that visual feedback can affect the
      spatial accuracy of movement with durations much less than 190 msec. We
      hypothesize that visual feedback can aid motor control via processes not
      associated with intermittent error corrections.

PMID- 15151870
TI  - Motor strategies in lifting movements: a comparison of adult and child
      performance.
AB  - The experiment compares the performances of children six to nine years old and
      adults in a simple, monoarticular lifting task. Overt behaviors, as described by
      the kinematic features of the movement, do not differ qualitatively in the two
      groups. The patterns of motor commands, as expressed by the electromyographic
      recordings, are however strikingly different. Adults plan the movement with a
      careful balance between agonist muscle activity and passive, viscoelastic forces,
      whereas children use both agonist and antagonist active forces. It is argued that
      the motor strategy adopted by adults depends upon an internal representation of
      the properties of the motor system and of the size/weight covariation in natural
      objects, and that this representation is not yet fully developed at nine years of
      age.

PMID- 15151872
TI  - The efficiency of skilled performance.
AB  - The observed ease or effort of performance has traditionally been considered an
      integral part of any definition of skill (e.g., Guthrie, 1935). Empirical
      investigations of skill learning and performance have, however, largely ignored
      the effort or efficiency with which the movement is performed. This situation has
      arisen despite the fact that in many skills, particularly athletic endurance
      events or industrial work tasks, efficiency of performance may be essential to
      the goal of the task. This paper focuses on the energy demand of various skills
      and its relationship to issues of learning, performance, and individual
      differences in preferred rhythm. It is shown that across a variety of tasks the
      individual's freely chosen work-rate is the most efficient. The significance of
      preferred rhythm to theoretical perspectives on rhythmic activity is discussed.

PMID- 15151873
TI  - Movement control in a reciprocal tapping task: a developmental study.
AB  - A cross-sectional approach was used to replicate and examine developmental
      flexibility in eye-hand relationships during alternate tapping performance. A
      group of 68 male subjects, 34 younger (mean 75.6 months) and 34 older (mean 128.9
      months) practiced 12 5-sec trials of alternate tapping in one of three accuracy
      conditions. Trials 2 and 11 were filmed to determine the eye movement index
      (EMI), a fraction relating eye movements (numerator) to alternate taps
      (denominator). Fractional EMI values close to 1 were labelled discontinuity and
      values closer to 0 (1/N) continuity. Accuracy variation tested the flexibility of
      EMI for developmental change, revealing that EMIs for older subjects were more
      continuous than for younger subjects at trial 11, but not at trial 2. Level of
      EMI was related to age and condition, while change in EMI due to practice was
      related to age. The data showed EMI strategy flexibility increased with age, and
      that faster tapping was afforded by less direct visual monitoring of the hand.

PMID- 15151874
TI  - Stimulus generalization and the peak shift with movement stimuli.
AB  - Stimulus generalization is suggested as an alternative method for examination of
      the "novelty" problem in motor learning. These experiments demonstrated that
      stimulus generalization occurs using simple movements as stimuli. The phenomenon
      of the "peak shift" in post-discrimination generalization gradients was also
      examined. The first experiment demonstrated that a peak shift occurred using
      linear movements as stimuli and that the magnitude of the peak shift increased as
      the difference between the training stimuli decreased. The second experiment
      showed similar results when the stimuli consisted of a range of movements rather
      than single movement length. The final experiment provided evidence that
      perception of movement length is influenced by the magnitude of an immediately
      preceding movement. The relevance of these studies to current motor-learning
      theory is discussed.

PMID- 15151875
TI  - The development of walking: new findings and old assumptions.
AB  - I have argued that a behavioral-cognitive perspective may shed light on some
      aspects of motor development generally, and unaided walking, specifically.
      Individual components of walking-stepping, standing, and placing, for example-are
      present at birth and can be maintained with practice. Moreover, consistent use
      can produce an earlier onset of unaided walking. Nonetheless, independent erect
      locomotion rarely occurs before about 9 months in most societies, implying that
      there is a maturational constraint. Independent research on changes in the
      quality of object use imply that the maturational limitation may be cognitive, in
      part. Changes in motor development-both the onset of unaided walking and the
      emergence of functional use-may be dictated by an underlying change in
      information processing ability. It is hypothesized that the infant's capacity to
      generate ideas or access different associations from memory rapidly may define
      the nature of this change. Improved access to memory may permit the necessary
      integrative capacity for balance and coordination to occur, thereby permitting
      unaided walking to develop. Weiss and Zelazo found that the capacity to perform
      two distinct actions in rapid succession in an independent environment-water-also
      appears to emerge from about 9 through 12 months. Not only may a cognitive change
      influence motor development, but mental and motor ability may develop
      asynchronously in some instances-a particularly important implication for
      developmental assessment. Procedures to distinguish information processing
      ability independent of gross and fine motor measures and productive language can
      lead to treatment that will reduce delays on conventional tests and contribute to
      the validity of this argument.

PMID- 15151876
TI  - Learning to walk is still an "old" problem: a reply to Zelazo (1983).
AB  - Zelazo (1983) proposes that two cognitive prerequisites are necessary for the
      development of locomotion: The conversion of neo-natal reflexive stepping into
      instrumental behavior and a shift from stereotypical to relational play. I argue
      that these cognitive assumptions are unnecessary. The disappearance of neo-natal
      stepping can be explained as a result of increasing leg mass, and the retention
      of this reflex with practice may be simply an exercise effect. Comparative and
      evolutionary evidence suggests that locomotion is not associated with abstract
      reasoning ability. Learning to walk is a complex, gradual process of maturation
      of motivation, the integration of subcortical pattern-generating centers with the
      neural substrate for control of posture and balance, and important changes in
      body proportions and bone and muscle strength. The control of walking is likely
      the province of mechanism phylogenetically more primitive than the human cerebral
      cortex. There is no need to invoke cortical explanations when more simple ones
      are sufficient.

PMID- 15151877
TI  - Time requirements of changes in program and parameter variables in rapid ongoing
      movements.
AB  - Two experiments investigated the differences in processing time requirements of
      two types of modifications of a rapid ongoing movement. In response to a signal
      presented at either 0, 100, or 200 msec after initiation of a 400-msec horizontal
      arm movement, subjects attempted to either increase the speed of the movement or
      to reverse it. EMG modification latencies were shorter in the former condition
      than in the latter indicating a difference in processing-time requirement between
      modification types. The results support the generalized motor program hypothesis
      of Pew (1974) and Schmidt (1976) in that increasing the speed of an ongoing
      movement may require modification of a parameter variable while reversing
      movement direction requires the implementation of a new motor program.

PMID- 15151878
TI  - Mechanism involvement during skill imagery.
AB  - Explanations of the effects of initial mental imagery practice on the subsequent
      performance of a motor task may be divided into two categories. In-flow
      explanations propose that proprioceptive feedback generated during imagery
      practice serves as the underlying mechanism while outflow explanations claim that
      cognitive operations (e.g., motor programs) generated during skill imagery serve
      as the basis for physical performance. A test of these two models was conducted
      by comparing unilateral and bilateral transfer in a rotary pursuit task following
      either imagery or physical practice (cf. Wallace, 1977). The results showed that
      all transfer groups produced positive transfer relative to a no-practice control
      group. Further, unilateral transfer was greater than bilateral transfer for
      physical practice. There was no difference between unilateral and bilateral
      transfer for imagery practice. These data were interpreted as evidence for an
      outflow explanation of skill imagery.

PMID- 15151879
TI  - Programming precision in repetitive tapping.
AB  - The present paper reports an experiment using the Fitts' tapping paradigm. It is
      concerned with a comparison of movement times and accuracy during blind and
      visual repetitive tapping. A blind condition was used to investigate rapid aiming
      movements under motor program control, whilst visual aiming was used to assess
      the role of visual feedback for control purposes. Subjects in the blind
      conditions were able to replicate the amplitude specifications of the task,
      whereas effective target width was constant for a set amplitude and did not
      reflect specified target width. Subjects, furthermore, responded more rapidly
      when tapping blind. These results are discussed in terms of the magnitude of
      forces being attempted as a result of performing a set amplitude, and the role of
      visual feedback.

PMID- 15151881
TI  - Capacity to vary writing hand/posture in relation to the Levy and Reid model for
      control of writing.
AB  - Inherent in Levy and Reid's (1978) neurological model for the control of writing
      hand/posture were implications pertaining to the capacity of people to vary their
      hand/posture when writing. These implications were formulated into the writing
      variation hypothesis. The skill with which right-normal, left-inverted, and left
      normal writers were able to write using hand/postures other than their preferred
      one was examined. The resulting performance was incompatible with Levy and Reid's
      neurological model. Whether or not subjects wrote with their preferred hand
      seemed more important than which posture they used.

PMID- 15151880
TI  - Processes controlling human movement: neuromotor constraints on American Sign
      Language.
AB  - The study of sign languages provides a promising vehicle for investigating
      language production because the movements of the articulators in sign are
      directly observable. Movement of the hands and arms is an essential element not
      only in the lexical structure of American Sign Language (ASL), but most
      strikingly, in the grammatical structure of ASL: It is in patterned changes of
      the movement of signs that many grammatical attributes are represented. The
      "phonological" (formational) structure of movement in ASL surely reflects in part
      constraints on the channel through which it is conveyed. We evaluate the relation
      between one neuromotor constraint on movement-regulation of final position rather
      than of movement amplitude-and the phonological structure of movement in ASL. We
      combine three-dimensional measurements of ASL movements with linguistic analyses
      of the distinctiveness and predictability of the final position (location) versus
      the amplitude (length). We show that final position, not movement amplitude, is
      distinctive in the language and that a phonological rule in ASL predicts
      variation in movement amplitude-a development which may reflect a neuromuscular
      constraint on the articulatory mechanism through which the language is conveyed.

PMID- 15151882
TI  - Parallel ocular and manual tracking responses to a continuously moving visual
      target.
AB  - Continuous ocular and manual tracking of the same visual target moving
      horizontally in sinusoids at 0.75 Hz was measured by lag, RMS Error, and Gain.
      The best measures of accuracy of tracking, error and lag, were remarkably similar
      in the two systems and were affected similarly by presence of a background and
      changes in predictability of target movement. Details of within-system
      performance varied despite the over-all parallels. Gain was different in
      adjustment of proportion of saccadic to pursuit movement was affected by the
      presence of the hand, even though this did not affect tracking accuracy. The over
      all parallel of response adjustment suggests that a suprasystem decision-maker
      sets general response goals and each motor system adjusts output details to match
      these goals.

PMID- 15151883
TI  - Amending movements: the relationship between degree of mechanical disturbance and
      outcome accuracy.
AB  - This paper examines the relationship between the degree of a mechanical
      disturbance, outcome accuracy, and amendment times to produce response
      corrections. Movement time error and amendment times were generated by
      systematically increasing the duration of acceleration and deceleration
      perturbations. Subjects produced discrete timing responses (700 msec-70 degrees)
      during which perturbations were interjected into the ongoing movement on random
      trials. Amendment times were generated from acceleration curves along with a
      number of related kinematic parameters (e.g., Movement Time, Peak Acceleration).
      The results showed that as the degree of the mechanical disturbance increased,
      timing error and amendment times to the perturbations also increased. At low
      force levels, the percentage of accurate responses to a decelerating perturbation
      was approximately equal to the percentage of accurate responses for control
      trials. As force level increased, however, timing error increased and the
      percentage of accurate responses decreased. in addition, as the magnitude of the
      disturbance increased, changes occurred in the kinematic properties of the
      perturbed movements which contributed toward the degree of outcome accuracy of
      the response. Collectively, the results are discussed in relation to an error
      correction system that operates in an interactive fashion based on the
      characteristics of the error and the constraints of the task.

PMID- 15151884
TI  - The acquisition of maximal isometric plantar flexor strength: a force-time curve
      analysis.
AB  - A paradigm involving the static force-time curve was used to study the mechanisms
      through which gains in maximal isometric strength are achieved during repeated
      testing. Twelve males performed three maximal contractions of the plantar flexors
      on each of six test days. Each contraction was executed as rapidly as possible,
      with the force recorded on a rapidly moving pen recorder. Although highly
      significant increases in maximal plantar flexor strength occurred over the six
      days, no changes were seen in the maximal rate of tension development. However,
      assessment of the amount of force reached at absolute time intervals revealed
      that more force was attained at the early time intervals on the first few days of
      testing than on the later days, indicating a distinct change in the shape of the
      static force-time curve. Several neural mechanisms are suggested to explain the
      alteration in shape of the static force-time curve which accompanies the
      acquisition of maximal strength.

PMID- 15151885
TI  - Variable error: variance-covariance heterogeneity, block size and type L error
      rates.
AB  - The degree to which blocked (VE) data satisfies the assumptions of compound
      symmetry required for a repeated measures ANOVA was studied. Monte Carlo
      procedures were used to study the effect of violation of this assumption, under
      varying block sizes, on the Type l error rate. Populations of 10,000 subjects for
      each of two groups, the underlying variance-covariance matrices reflecting a
      specific condition of violation of the homogeneity of covariance assumptions, was
      generated based on each of three actual experimental data sets. The data were
      blocked in various ways, VE calculated, and subsequently analyzed by a repeated
      measures ANOVA. The complete process was replicated for four covariance
      homogeneity conditions for each of the three data sets, resulting in a total of
      22,000 simulated experiments. Results indicated that the Type l error rate
      increases as the degree of heterogeneity within the variance-covariance matrices
      increases when raw (unblocked) data are analyzed. With VE, the effects of within
      matrix heterogeneity on the Type l error rate are inconclusive. However, block
      size does seem to affect the probability of obtaining a significant interaction,
      but the nature of this relationship is not clear as there does not appear to be
      any consistent relationship between the size of the block and the probability of
      obtaining significance. For both raw and VE data there was no inflation in the
      number of Type l errors when the covariances within a given matrix were
      homogeneous, regardless of the differences between the group variance-covariance
      matrices.

PMID- 15151886
TI  - Explorations of individual differences relevant to high level skill.
AB  - Past research has uncovered few broad abilities that underlie high skill. In this
      paper, attempts to isolate three different abilities of potential relevance to
      skill are described. No evidence was found for a general time-sharing ability in
      common to different kinds of tasks. Modest evidence was found for a trait of
      attentional flexibility. That trait could potentially be of use in predicting
      success for skills that require rapid shifts of attention because of rapidly
      changing task demands. Finally, the rate of repetitive activity is correlated
      across different muscle groups. For example, finger tapping speed is correlated
      with foot tapping speed, suggesting a common rate limiting factor. In turn, those
      rates predict handwriting speed and, according to Book (1924), championship
      typing.

PMID- 15151887
TI  - Programming time as a function of response duration: a replication of "dit-dah"
      without possible guessing artifacts.
AB  - Reaction time was longer prior to longer-lasting pressing responses for low
      probability, unanticipated movements. By contrast, reaction time was independent
      of response duration for high probability, anticipated movements. This replicates
      and extends previous findings for choice and simple reaction time in the "dit
      dah" paradigm. The present results (unanticipated responses) cannot be given a
      selective anticipation interpretation because the comparison is between responses
      which are never anticipated. The previous paradigm was open to an alternative
      interpretation in which selective anticipation of dit rather than dah could have
      produced the differences in choice reaction time. Confirmation of the finding
      that variations in required response duration lead to differences in reaction
      time supports the view that the underlying parameter of "complexity" in the
      "memory drum theory" may be response duration.

PMID- 15151888
TI  - The specification of digit and duration during motor programming: a new method of
      precueing.
AB  - This experiment manipulated digit uncertainty, duration uncertainty, and response
      duration (dit or dah) in a choice reaction time key press task. A new method of
      precueing was developed that effectively "precued" the digit and/or the duration
      of the key press task without confounding the number of stimulus response
      alternatives with the levels of uncertainty of digit and duration. When the
      duration of the response was certain, there were no RT differences between dit
      and dah responses, however, when duration was uncertain, RT to dah responses were
      longer than dit. In addition, level of duration uncertainty and digit uncertainty
      produced an overadditive interaction upon RT. These results are discussed in
      terms of generalized motor programs and a feature construction hypothesis. In
      addition, these results support the view that precueing of movement dimensions
      can be accomplished without confounding the number of stimulus response
      alternatives and the uncertainties of movement dimensions.

PMID- 15151889
TI  - Cognitive factors in simple reactions: a developmental study.
AB  - In an exploration of factors underlying the developmental increase in the speed
      of simple reaction to an auditory stimulus, two experiments were undertaken, with
      subjects aged 4, 10, and 20. The first experiment demonstrated that provision of
      visual feedback caused improvement for younger subjects but not for adults,
      whereas neither practice nor variable feedback caused any differential change.
      The second experiment was a simulated game where visual feedback was contingent
      on a "hit" on the previous trial. Following a hit the target moved faster,
      following a miss, slower. Practice caused a considerable improvement for the 4
      year old subjects, but not for the older subjects. The nature it or miss feedback
      on the previous trial had powerful effects on the simple reaction times. For all
      subjects, a miss resulted in a subsequent substantial increase in speed on the
      next trial. Following a hit, the adults were unaffected, but the youngest
      subjects were substantially slower. The results are interpreted in terms of
      inappropriate relaxation following a hit for the 4-year old subjects, with active
      strategic behavior by the adults, following a miss. It is concluded that one
      variable (incentive provided by a miss) affects simple reaction for all ages,
      that two (disincentive provided by a hit, and visual feedback) differentially
      affect subjects of different ages, and that a fourth (use of a "trade-off"
      strategy) is not available to the youngest subjects.

PMID- 15151891
TI  - Encoding specificity: a reply to Croker (1981).
AB  - Crocker's (1981) comment on the Lee and Hirota (1980) paper essentially raises
      two issues. First, objection is made to the applicability of the encoding
      specificity principle to the resuits found in our study. Second, on a more
      general level, Crocker questions the heuristic value of utilizing theoretical
      issues in non-motor domains to guide scientific experimentation in the study of
      motor behavior. In this reply I posit that Crocker's reservations about encoding
      specificity are based upon improper theoretical and methodological
      considerations. Regarding the more philosophical issue however, I argue that
      Crocker's view may be counterproductive to progress in the area of memory
      research.

PMID- 15151892
TI  - Repetition and lag effects in movement recognition.
AB  - Whether repetition and lag improve the recognition of movement patterns was
      investigated. Recognition memory was tested for one repetition, two-repetitions
      massed, and two-repetitions distributed with movement patterns at lags of 3, 5,
      7, and 13. Recognition performance was examined both immediately afterwards and
      following a 48 hour delay. Both repetition and lag effects failed to be
      demonstrated, providing some support for the claim that memory is unaffected by
      repetition at a constant level of processing (Craik & Lockhart, 1972). There was,
      as expected, a significant decrease in recognition memory following the retention
      interval, but this appeared unrelated to repetition or lag.

PMID- 15151893
TI  - The relationship of impulse to response timing error.
AB  - This paper examines the relationship between response impulse and timing error in
      200 msec discrete timing responses over a range of movement velocities and system
      masses. The results from two experiments showed that variable timing error
      decreased as both movement velocity and the mass of the system to be moved
      increased. The variability of force proportional to force (measured either as
      impulse or peak force) decreased curvilinearly as force out-put increased. The
      correlations between each of these parameters and variable timing errors,
      calculated on a group mean basis, ranged between.91 and.95. The ability to
      predict the movement time outcome of each individual trial from impulse-related
      parameters was considerably reduced, although the relationship between the
      various kinematic and kinetic parameters did strengthen as the movement velocity
      approached maximum. Collectively, the findings show the size of impulse is
      related to movement timing error, although it is premature argue that impulse
      variability is a causal agent of timing error.

PMID- 15151894
TI  - Rapid error correction during human arm movements: evidence for central
      monitoring.
AB  - Studies were made of rapid error correction movements in eight subjects
      performing a visually guided tracking task involving flexion-extension movements
      about the elbow. Subjects were required to minimize reaction times in this two
      choice task. Errors in initial movement direction occurred in about 3% of the
      trials. Error correction times (time from initiation to reversal of movement in
      incorrect direction) ranged from 30-150 ms. The first sing of correction of the
      error movement was a suppression of the electromyographic (EMG) activity in the
      muscle producing the error movement. This suppression started as early as 20-40
      ms after the initiation of the error-related EMG activity and as much as 50 ms
      before any overt sign of limb movement. The correction of the error movement was
      also accompanied by an increase in the drive to the muscle which moved the arm in
      the correct direction. This increased activity always occurred after the
      initiation of the error movement. it is concluded that the first step in the
      error correction, suppression of drive to the muscle producing the error
      movement, cannot be based on information from the moving limb. It is thus
      suggested that this earliest response to the error movement is based on central
      monitoring of the commands for movement.

PMID- 15151890
TI  - Encoding specificity in short-term memory for movement information: a comment on
      Lee and Hirota (1980).
AB  - Lee and Hirota (1980) claimed to provide evidence for the encoding specificity
      principle for movement information. I argue that their interpretations are
      confounded by methodological and theoretical factors. I further suggest that
      their findings are compatible with generation-recognition models of memory
      retrieval and thus, their study does not provide an adequate test for
      investigating encoding-retrieval relations. Finally, I discuss the problems and
      dangers of borrowing theoretical concepts from verbal domain and applying them
      indiscriminately to the motor domain.

PMID- 15151895
TI  - On separability of and interference between tracking dimensions in dual-axis
      tracking.
AB  - Time-shared tasks may conceivably be separable or integral. A case in which the
      question of separability seems quite relevant is dual-axis tracking. To test the
      interaction between tracking dimensions, we first studied whether they interfere
      with each other. Practiced subjects performed tracking on one or two axes, with
      or without feedback indicators and with or without a requirement to allocate
      resources unevenly between axes. They also performed with or without a concurrent
      binary classification of visually presented digits which were presented within a
      moving square that served as the target for tracking. Small deficits were found
      in the performance of both tracking and digit classification when performed
      together. However, the conditions of tracking did not have a discernible effect
      on either tracking or digit classification. Hence, the introduction of a second
      tracking axis probably does not have harmful consequences either on tracking
      itself or on any other task time-shared with tracking. Further studies were
      conducted to examine whether the absence of an effect of number of tracking axes
      is dues to their integrality. Ordinary position tracking was paired either with
      another similar task on the other axis or with a novel sort of tracking in which
      subjects had to continually match sizes of moving rectangles. Tasks were paired
      under both divided-attention and focused-attention instructions. No interference
      on position tracking was observed even when the types of task on the two axes
      differed, and no other evidence for integrality of the homogeneous task pairs was
      found.

PMID- 15151896
TI  - Binary choice reaction time as a function of the relationship between durations
      and forms of responses.
AB  - In a choice between responding with the left or right hand, some kinds of
      differences between the movements increase RT (Reaction Time) while others do
      not. Of the first kind are differences in form, while differences in the finger
      used are of the latter kind. In previous experiments differences in form were
      confounded with differences in duration. Since there is some indication that a
      difference in duration is sufficient to lengthen RT, both characteristics were
      varied separately. It turned out that a difference in form (duration being
      constant) has essentially the same effects as a difference in duration (form
      being constant): Mean RT is longer, variability of RT and MT (movement time) is
      larger, and frequency of choice errors is smaller than in choice between
      identical movements. These effects, which seem to be associated with choice
      between movements of different temporal patterns, are interpreted in terms of
      advance specification of movement parameters. Additional results on the
      relationship between response duration and RT suggest that RT does not depend on
      duration (or velocity) per se, but on how much the duration deviates from
      quickest performance.

PMID- 15151897
TI  - Programming time as a function of number of movement parts and changes in
      movement direction.
AB  - The question of whether changes seen in simple reaction time (SRT) as a function
      of response complexity (i.e., number of movement parts) should be considered as
      differences in the time needed to centrally program a motor response was
      addressed. Using a large-scale tapping response, 14 subjects contacted from one
      to five targets positioned in a straight line, while a second group of 14
      subjects executed 90 degrees changes in direction in striking the targets.
      Results revealed that mean SRT and mean premotor time increased linearly as the
      number of movement parts increased, regardless of whether changes in movement
      direction had to be programmed, with the greatest increase occurring between one
      , and two-part responses. Increases in motor time were not sufficient to account
      for the sizeable SRT effect. These findings support the position of increased
      central programming time for more complex responses, and also help establish some
      of the boundaries of the complexity effect.

PMID- 15151898
TI  - Power spectral density analysis of lateral human standing sway.
AB  - A number of investigators have used power spectral density (PSD) analysis to try
      to identify and quantify various sensory systems which are involved in upright
      standing. Using PSD analysis, over a frequency range from 0.02-2.5 Hz, the
      present study examined two trials of lateral sway in each of 80 men. The results
      showed that little change occurred in PSD values between the first and second
      trials. Exponential curves were fit to the averaged trials data of each subject.
      The values of the parameter estimates obtained from the curve-fitting were
      regressed on the values of various direct, and derived anthropometric variables
      to try to explain the variance of the parameter estimates in terms of the
      anthropometrics. The subject's center of gravity location accounted for no more
      than 15.8% of the parameter variance, whereas the remaining anthropometrics
      explained even less. The overall averaged data suggest that three functions
      (related to visual, vestibular, and proprioceptive processes) may underlie the
      sway pattern over this frequency range. PSD curves of individuals with a history
      of high-level athletic activity clearly differed from those of sedentary
      subjects.

PMID- 15151899
TI  - On the nature of the probe reaction-time task to uncover the attentional demands
      of movement.
AB  - McLeod (1980) reported some findings which showed that no phase of a movement was
      more attention-demanding than the other phases, contrary to all the results
      previously reported (e.g., Ells, 1973; Glencross, 1980). However, McLeod used a
      paradigm in which the two tasks were serial. Each task consisted of a series of
      50 reaction time (RT) trials and/or 50 aiming movement trials. In addition to
      this, the interval of time between a response and the following signal within
      each series was constant. In order to try to replicated McLeod's findings, two
      experiments were conducted in which the response-signal interval was manipulated.
      The hypothesis was that time certainty associated with a constant interval would
      facilitate the allocation of time and would thus artificially reduce the
      interference between tasks. In Experiment 1, manual responses were used for the
      RT task; in Experiment II, they were vocal. Manipulation of the response-signal
      interval does not change one of the conclusions reached by McLeod: when the RT
      task involves vocal responses and the results on the RT task are analyzed in
      terms of response rather than stimulus arrival during the movement, then there is
      no phase of the movement which is more attention-demanding than the other phases.
      However, the results of Experiment II in which both the vocal RT task and the
      movement task significantly deteriorated in the dual-task condition were taken as
      an indication that the movement studied involved central attentional demands.

PMID- 15151900
TI  - A note on the speed-amplitude function in movement control.
AB  - An experiment is reported that documents the maximum average speed-amplitude
      relationship across the full range of motion for elbow flexion. Minimum movement
      time increased as a negative exponential within the movement range up to 94-97%
      of the maximum range of motion. At this point a discontinuity occurred with
      movement time increasing at an increasing rate probably due to anatomical and
      morphological constraints. These results suggest that the maximum average
      velocity-amplitude boundary to the movement speed-accuracy relationship is
      curvilinear. Kinematic analysis of the movements as a function of range of motion
      suggests that a simple pulse-step model of movement control cannot account for
      the present findings.

PMID- 15151901
TI  - Cooperative attachment of cross bridges predicts regulation of smooth muscle
      force by myosin phosphorylation.
AB  - Serine 19 phosphorylation of the myosin regulatory light chain (MRLC) appears to
      be the primary determinant of smooth muscle force development. The relationship
      between MRLC phosphorylation and force is nonlinear, showing that phosphorylation
      is not a simple switch regulating the number of cycling cross bridges. We
      reexamined the MRLC phosphorylation-force relationship in slow, tonic swine
      carotid media; fast, phasic rabbit urinary bladder detrusor; and very fast, tonic
      rat anococcygeus. We found a sigmoidal dependence of force on MRLC
      phosphorylation in all three tissues with a threshold for force development of
      approximately 0.15 mol P(i)/mol MRLC. This behavior suggests that force is
      regulated in a highly cooperative manner. We then determined whether a model that
      employs both the latch-bridge hypothesis and cooperative activation could
      reproduce the relationship between Ser(19)-MRLC phosphorylation and force without
      the need for a second regulatory system. We based this model on skeletal muscle
      in which attached cross bridges cooperatively activate thin filaments to
      facilitate cross-bridge attachment. We found that such a model describes both the
      steady-state and time-course relationship between Ser(19)-MRLC phosphorylation
      and force. The model required both cooperative activation and latch-bridge
      formation to predict force. The best fit of the model occurred when binding of a
      cross bridge cooperatively activated seven myosin binding sites on the thin
      filament. This result suggests cooperative mechanisms analogous to skeletal
      muscle that will require testing.

PMID- 15151902
TI  - Involvement of G protein betagamma-subunits in diverse signaling induced by
      G(i/o)-coupled receptors: study using the Xenopus oocyte expression system.
AB  - We studied the functions of betagamma-subunits of G(i/o) protein using the
      Xenopus oocyte expression system. Isoproterenol (ISO) elicited cAMP production
      and slowly activating Cl(-) currents in oocytes expressing beta(2)-adrenoceptor
      and the protein kinase A-dependent Cl(-) channel encoded by the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. 5-Hydroxytryptamine (5-HT), [d
      Ala(2), d-Leu(5)]-enkephalin (DADLE), and baclofen enhanced ISO-induced cAMP
      levels and CFTR currents in oocytes expressing beta(2)-adrenoceptor-CFTR and 5
      HT(1A) receptor (5-HT(1A)R), delta-opioid receptor, or GABA(B) receptor,
      respectively. 5-HT also enhanced pituitary adenylate cyclase activating peptide
      (PACAP) 38-induced cAMP levels and CFTR currents in oocytes expressing PACAP
      receptor, CFTR and 5-HT(1A)R. The 5-HT-induced enhancement of G(s)-coupled
      receptor-mediated currents was abrogated by pretreatment with pertussis toxin
      (PTX) and coexpression of G transducin alpha (G(t)alpha). The 5-HT-induced
      enhancement was further augmented by coexpression of the Gbetagamma-activated
      form of adenylate cyclase (AC) type II but not AC type III. Thus betagamma
      subunits of G(i/o) protein contribute to the enhancement of G(s)-coupled receptor
      mediated responses. 5-HT and DADLE did not elicit any currents in oocytes
      expressing 5-HT(1A)R or delta-opioid receptor alone. They elicited Ca(2+)
      activated Cl(-) currents in oocytes coexpressing these receptors with the
      Gbetagamma-activated form of phospholipase C (PLC)-beta2 but not with PLC-beta1.
      These currents were inhibited by pretreatment with PTX and coexpression of
      G(t)alpha, suggesting that betagamma-subunits of G(i/o) protein activate PLC
      beta2 and then cause intracellular Ca(2+) mobilization. Our results indicate that
      betagamma-subunits of G(i/o) protein participate in diverse intracellular
      signals, enhancement of G(s)-coupled receptor-mediated responses, and
      intracellular Ca(2+) mobilization.

PMID- 15151903
TI  - Calcium-dependent regulation of calcium efflux by the cardiac sodium/calcium
      exchanger.
AB  - Allosteric regulation by cytosolic Ca2+ of Na(+)/Ca2+ exchange activity in the
      Ca2+ efflux mode has received little attention because it has been technically
      difficult to distinguish between the roles of Ca2+ as allosteric activator and
      transport substrate. In this study, we used transfected Chinese hamster ovary
      cells to compare the Ca2+ efflux activities in nontransfected cells and in cells
      expressing either the wild-type exchanger or a mutant, Delta(241-680), that
      operates constitutively; i.e., its activity does not require allosteric Ca2+
      activation. Expression of the wild-type exchanger did not significantly lower the
      cytosolic Ca2+ concentration ([Ca2+](i)) compared with nontransfected cells.
      During Ca2+ entry through store-operated Ca2+ channels, Ca2+ efflux by the wild
      type exchanger became evident only after [Ca2+](i) approached 100-200 nM. A
      subsequent decline in [Ca2+](i) was observed, suggesting that the activation
      process was time dependent. In contrast, Ca2+ efflux activity was evident under
      all experimental conditions in cells expressing the constitutive exchanger
      mutant. After transient exposure to elevated [Ca2+](i), the wild-type exchanger
      behaved similarly to the constitutive mutant for tens of seconds after [Ca2+](i)
      had returned to resting levels. We conclude that Ca2+ efflux activity by the wild
      type exchanger is allosterically activated by Ca2+, perhaps in a time-dependent
      manner, and that the activated state is briefly retained after the return of
      [Ca2+](i) to resting levels.

PMID- 15151904
TI  - Real-time imaging of peroxisome proliferator-activated receptor-gamma coactivator
      1alpha promoter activity in skeletal muscles of living mice.
AB  - In response to sustained increase in contractile activity, mammalian skeletal
      muscle undergoes adaptation with enhanced mitochondrial biogenesis and fiber type
      switching. The peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha) was recently identified as a key regulator for these adaptive
      processes. To investigate the sequence elements in the PGC-1alpha gene that are
      responsible for activity-dependent transcriptional activation, we have
      established a unique system to analyze promoter activity in skeletal muscle of
      living mice. Expression of PGC-1alpha-firefly luciferase reporter gene in mouse
      tibialis anterior muscle transfected by electric pulse-mediated gene transfer was
      assessed repeatedly in the same muscle by using optical bioluminescence imaging
      analysis before and after low-frequency (10 Hz) motor nerve stimulation. Nerve
      stimulation (2 h) resulted in a transient 3-fold increase (P < 0.05) in PGC
      1alpha promoter activity along with a 1.6-fold increase (P < 0.05) in endogenous
      PGC-1alpha mRNA. Mutation of two consensus myocyte enhancer factor 2 (MEF2)
      binding sites (-2901 and -1539) or a cAMP response element (CRE) (-222)
      completely abolished nerve stimulation-induced increase in PGC-1alpha promoter
      activity. These findings provide direct evidence that contractile activity
      induced PGC-1alpha promoter activity in skeletal muscle is dependent on the MEF2
      and the CRE sequence elements. The experimental methods used in the present study
      have general applicability to studies of gene regulation in muscle.

PMID- 15151905
TI  - Interleukin-6-induced JAK2/STAT3 signaling pathway in endothelial cells is
      suppressed by hemodynamic flow.
AB  - Endothelial cells (ECs) are constantly exposed to shear stress, the action of
      which triggers signaling pathways and cellular responses. During inflammation,
      cytokines such as IL-6 increase in plasma. In this study, we examined the effects
      of steady flow on IL-6-induced endothelial responses. ECs exposed to IL-6
      exhibited STAT3 activation via phosphorylation of Tyr705. However, when ECs were
      subjected to shear stress, shear force-dependent suppression of IL-6-induced
      STAT3 phosphorylation was observed. IL-6 treatment increased the phosphorylation
      of JAK2, an upstream activator of STAT3. Consistently, shear stress significantly
      reduced IL-6-induced JAK2 activation. Pretreatment of ECs with an inhibitor of
      MEK1 did not alter this suppression by shear stress, indicating that
      extracellular signal-regulated kinase (ERK1/2) was not involved. However,
      pretreatment of ECs with an endothelial nitric oxide synthase inhibitor (nitro-l
      arginine methyl ester) attenuated this inhibitory effect of shear stress on STAT3
      phosphorylation. Shear stress-treated ECs displayed decreased nuclear
      transmigration of STAT3 and reduced STAT3 binding to DNA. Intriguingly, ECs
      exposed to IL-6 entered the cell cycle, as evidenced by increasing G(2)/M phase,
      and shear stress to these ECs significantly reduced IL-6-induced cell cycle
      progression. STAT3-mediated IL-6-induced cell cycle was confirmed by the
      inhibition of the cell cycle in ECs infected with adenovirus carrying the
      inactive mutant of STAT3. Our study clearly shows that shear stress exerts its
      inhibitory regulation by suppressing the IL-6-induced JAK2/STAT3 signaling
      pathway and thus inhibits IL-6-induced EC proliferation. This shear force
      dependent inhibition of IL-6-induced JAK2/STAT3 activation provides new insights
      into the vasoprotective effects of steady flow on ECs against cytokine-induced
      responses.

PMID- 15151907
TI  - Protective role of extracellular chloride in fatigue of isolated mammalian
      skeletal muscle.
AB  - A possible role of extracellular Cl(-) concentration ([Cl(-)](o)) in fatigue was
      investigated in isolated skeletal muscles of the mouse. When [Cl(-)](o) was
      lowered from 128 to 10 mM, peak tetanic force was unchanged, fade was exacerbated
      (wire stimulation electrodes), and a hump appeared during tetanic relaxation in
      both nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus
      (EDL) muscles. Low [Cl(-)](o) increased the rate of fatigue 1) with prolonged,
      continuous tetanic stimulation in soleus, 2) with repeated intermittent tetanic
      stimulation in soleus or EDL, and 3) to a greater extent with repeated tetanic
      stimulation when wire stimulation electrodes were used rather than plate
      stimulation electrodes in soleus. In nonfatigued soleus muscles, application of 9
      mM K(+) with low [Cl(-)](o) caused more rapid and greater tetanic force
      depression, along with greater depolarization, than was evident at normal [Cl(
      )](o). These effects of raised [K(+)](o) and low [Cl(-)](o) were synergistic.
      From these data, we suggest that normal [Cl(-)](o) provides protection against
      fatigue involving high-intensity contractions in both fast- and slow-twitch
      mammalian muscle. This phenomenon possibly involves attenuation of the
      depolarization caused by stimulation- or exercise-induced run-down of the
      transsarcolemmal K(+) gradient.

PMID- 15151906
TI  - Adrenergic modulation of splenic macrophage cytokine release in polymicrobial
      sepsis.
AB  - Enhanced adrenergic stimulation and catecholamine release are important
      components of the pathophysiology of sepsis. Under physiological conditions,
      adrenergic stimulation has been shown to be a negative regulator of
      proinflammatory cytokine production through increasing IL-10 production. Here we
      have investigated if adrenergic stimulation similarly inhibits TNF-alpha and IL-6
      production by splenic macrophages isolated from a polymicrobial sepsis model.
      Male B(6)D(2)F(1) mice were subjected to sham (S), laparotomy (Lap), and cecal
      ligation and puncture (CLP) under anesthesia. Splenic macrophages were isolated
      72 h after the initial injury and were stimulated with endotoxin (LPS) in the
      presence and absence of epinephrine. Compared with S and Lap, splenic macrophages
      from the CLP group produced significantly less TNF-alpha and IL-6 and more IL-10
      when stimulated with LPS. Macrophage cultures from CLP animals incubated with
      either epinephrine or IL-10 for 2 h had significantly reduced TNF-alpha and IL-6
      release in response to LPS. However, similar cultures pretreated with IL-10
      antibody before the addition of exogenous epinephrine failed to reverse the
      attenuation of LPS-stimulated cytokines. Pretreatment of macrophage cultures with
      beta(2)- (ICI-118551) but not beta(1)-adrenergic (atenolol) receptor antagonists
      reversed the epinephrine-mediated cytokine attenuation following LPS treatment.
      Data are also presented that demonstrate the involvement of protein kinase A
      activation with adrenergic agonist but not with IL-10 stimulation. Taken
      together, these findings suggest that adrenergic mechanisms may influence
      peripheral tissue macrophage inflammatory cytokine response following trauma and
      sepsis, independent of the effects of IL-10.

PMID- 15151908
TI  - Expression and localization of rat NBC4c in liver and renal uroepithelium.
AB  - Previous studies provided functional evidence for electrogenic Na(+)-HCO(3)(-)
      cotransport in hepatocytes and in intrahepatic bile duct cholangiocytes. The
      molecular identity of the transporters mediating electrogenic sodium-bicarbonate
      cotransport in the liver is currently unknown. Of the known electrogenic Na(+)
      HCO(3)(-) cotransporters (NBC1 and NBC4), we previously showed that NBC4 mRNA is
      highly expressed in the liver. In the present study, we performed RT-PCR,
      immunoblotting, and immunohistochemistry to characterize the expression pattern
      of NBC4 in rat liver and kidney. For immunodetection, a polyclonal antibody
      against rat NBC4 was generated and affinity purified. Of the known human NBC4
      variants, only the rat NBC4c ortholog was detected by RT-PCR in rat liver, and
      the molecular mass of the NBC4c protein was approximately 145 kDa. NBC4c protein
      was expressed in hepatocytes and in the cholangiocytes lining the intrahepatic
      bile ducts. In hepatocytes, NBC4c was localized to the basolateral plasma
      membrane, whereas intrahepatic cholangiocytes stained apically. The NBC1
      electrogenic sodium cotransporter variants kNBC1 and pNBC1 were not detected by
      immunoblotting and immunohistochemistry in rat liver. The pattern of localization
      of NBC4c in the liver suggests that the cotransporter plays a role in mediating
      Na(+)-HCO(3)(-) cotransport in hepatocytes and intrahepatic cholangiocytes.
      Unlike the liver, the rat kidney expressed electrogenic sodium-bicarbonate
      cotransporter proteins kNBC1 and NBC4c. In kidney, NBC4c also had a molecular
      mass of approximately 145 kDa and was immunolocalized to uroepithelial cells
      lining the renal pelvis, where the cotransporter may play an important role in
      protecting the renal parenchyma from alterations in urine pH.

PMID- 15151909
TI  - Understanding why older people participate in clinical trials: the experience of
      the Scottish PROSPER participants.
AB  - BACKGROUND: over the next 20 years it is anticipated that there will be a
      significant increase in those aged 75 and over, and a consequent increase in
      cardiovascular disease, cancer and chronic illness. As this shift takes effect,
      there will be an increased need for treatment strategies that are of known
      benefit to this age group and a consequent rise in demand for clinical trials
      that are conducted specifically with the older population. Because factors that
      motivate older individuals to participate in clinical trials may differ from
      those that influence younger adults, it is important to evaluate the strategies
      used to encourage recruitment and retention and to determine how appropriate
      these are. AIM: evaluation of the reasons why subjects agree to participate in a
      controlled clinical trial of vascular disease prevention and the strategies used
      to improve compliance and protocol adherence. SETTING: Scotland. SUBJECTS: 2,520
      Prospective Study of Pravastatin in the Elderly at Risk participants, aged 70-82
      with either pre-existing vascular disease or at least one major vascular risk
      factor (hypertension, cigarette smoking, or diabetes mellitus). DESIGN OF STUDY:
      two-stage iterative survey. Stage I was exploratory. RESULTS: curiosity, or an
      interest in finding out more about the study, 'a desire to support research', and
      anticipated personal benefits, such as health screening, were the most important
      motivators for generating initial interest in the trial. Ongoing health
      monitoring was the most important recruitment and retention motivator (P =
      0.001). CONCLUSIONS: curiosity, self interest and altruism may act as motivators
      at different points in the study time-line. However, fostering positive
      relationships between staff and recruits, and keeping recruits informed about the
      progress of the study are likely to maximise the retention of older subjects to
      long-term trials.

PMID- 15151910
TI  - Cognitive decline with chronic meningitis secondary to a COX-2 inhibitor.
AB  - Non-steroidal anti-inflammatory drugs are currently being investigated as agents
      to reduce the incidence and progression of Alzheimer's disease. Paradoxically
      they have also been reported to induce deleterious effects on the central nervous
      system, including aseptic meningitis and cognitive decline in the elderly. We
      report a case of a 72-year-old woman who presented with a 6-week history of
      profound confusion whilst being treated with rofecoxib, a COX-2 inhibitor. Lumbar
      puncture demonstrated a lymphocytic pleocytosis with increased protein and normal
      glucose. Complete clinical remission occurred 5 days after the rofecoxib was
      ceased with no other cause found despite extensive investigation. This case
      illustrates that non-steroidal anti-inflammatory drugs, including the new COX-2
      inhibitors, can produce chronic lymphocytic meningitis, which may manifest as
      cognitive decline. This mechanism may account for other case reports and
      epidemiological evidence of the association between non-steroidal anti
      inflammatory drugs and confusion.

PMID- 15151911
TI  - Unmet treatment needs of older prisoners: a primary care survey.
AB  - BACKGROUND: little is known about the treatment needs of older prisoners and to
      what extent they are being met. SUBJECTS: representative sample of 203 sentenced
      prisoners aged 60 and over in 15 prisons in England and Wales. DESIGN: case notes
      were surveyed using a standardised proforma and information on current medication
      was collected. RESULTS: three-quarters of older prisoners were prescribed
      medication. Those with cardiovascular, respiratory and endocrine health problems
      were prescribed medication that was mostly appropriately targeted. In contrast,
      only 18% of inmates with recorded psychiatric morbidity were prescribed
      psychotropic medication. CONCLUSIONS: reviewing the medical records of older
      prisoners and considering the appropriateness of their current medication regime
      would be a primary care intervention that could significantly improve the health
      of this marginalized group.

PMID- 15151912
TI  - A randomised controlled trial of a care home rehabilitation service to reduce
      long-term institutionalisation for elderly people.
AB  - OBJECTIVES: to evaluate the effect of a care home rehabilitation service on
      institutionalisation, health outcomes and service use. DESIGN: randomised
      controlled trial, stratified by Barthel ADL index, social service sector and
      whether living alone. The intervention was a rehabilitation service based in
      Social Services old people's homes in Nottingham, UK. The control group received
      usual health and social care. PARTICIPANTS: 165 elderly and disabled hospitalised
      patients who wished to go home but were at high risk of institutionalisation (81
      intervention, 84 control). MAIN OUTCOME MEASURES: institutionalisation rates,
      Barthel ADL index, Nottingham Extended ADL score, General Health Questionnaire
      (12 item version) at 3 and 12 months, Health and Social Service resource use.
      RESULTS: the number of participants institutionalised was similar at 3 months
      (relative risk 1.04, 95% confidence intervals 0.65-1.65) and 12 months (relative
      risk 1.23, 95% confidence intervals 0.75-2.02). Barthel ADL Index, Nottingham
      Extended ADL score and General Health Questionnaire scores were similar at 3 and
      12 months. The intervention group spent significantly fewer days in hospital over
      3 and 12 months (mean reduction 12.1 and 27.6 days respectively, P < 0.01), but
      spent a mean of 36 days in a care home rehabilitation service facility.
      CONCLUSIONS: this service did not reduce institutionalisation, but diverted
      patients from the hospital to social services sector without major effects on
      activity levels or well-being.

PMID- 15151913
TI  - Loss of partner and suicide risks among oldest old: a population-based register
      study.
AB  - BACKGROUND: while mortality among the oldest old has improved over recent
      decades, these improvements are not reflected in the suicide mortality of this
      age group. We do not know the reasons why the suicide mortality is still very
      high among the oldest old. OBJECTIVE: the aim is to analyse the impact that loss
      of a partner has on the suicide risks of the oldest old (80+) compared to younger
      age groups. SUBJECTS: the entire Danish population aged 50 during 1994-1998 (n =
      1,978,527). METHODS: we applied survival analysis to calculate the changes in
      relative risk of suicide after a loss by using individual-level data. RESULTS:
      the majority of older persons who commit suicide are widowed, although only a
      relatively small proportion of the oldest old who commit suicide have experienced
      a recent loss of partner (men: 18%, women: 6%). In absolute terms, the oldest old
      men experience the highest increase in suicide risk immediately after the loss
      (15-fold; 95% CI 10.2-23.6) compared to middle-aged men who are still married.
      Oldest old men seem to suffer more from the loss and need longer time to recover
      than women. CONCLUSIONS: although a small proportion of oldest old who commit
      suicide have experienced a recent bereavement, there is a significant increase in
      the suicide risk during the first year after a bereavement, especially for men.
      However, the increased risk of suicide in the oldest old men may only in part be
      explained by the loss of a partner.

PMID- 15151915
TI  - The tight junction: a multifunctional complex.
AB  - Multicellular organisms are separated from the external environment by a layer of
      epithelial cells whose integrity is maintained by intercellular junctional
      complexes composed of tight junctions, adherens junctions, and desmosomes,
      whereas gap junctions provide for intercellular communication. The aim of this
      review is to present an updated overview of recent developments in the area of
      tight junction biology. In a relatively short time, our knowledge of the tight
      junction has evolved from a relatively simple view of it being a permeability
      barrier in the paracellular space and a fence in the plane of the plasma membrane
      to one of it acting as a multicomponent, multifunctional complex that is involved
      in regulating numerous and diverse cell functions. A group of integral membrane
      proteins-occludin, claudins, and junction adhesion molecules-interact with an
      increasingly complex array of tight junction plaque proteins not only to regulate
      paracellular solute and water flux but also to integrate such diverse processes
      as gene transcription, tumor suppression, cell proliferation, and cell polarity.

PMID- 15151914
TI  - Using targeted risk factor reduction to prevent falls in older in-patients: a
      randomised controlled trial.
AB  - BACKGROUND: falls and related injuries are known to be a significant problem for
      older people. There is evidence that identifying and addressing individual risk
      factors can reduce the incidence of falls in the community but no evidence of the
      effectiveness of targeted risk factor reduction methods applied to hospital in
      patients. OBJECTIVE: to test the efficacy of a targeted risk factor reduction
      core care plan in reducing risk of falling while in hospital. DESIGN: a group
      (ward) randomised trial. SETTING: elderly care wards and associated community
      units of a district general hospital in the North of England. SUBJECTS: all
      elderly patients who received care in eight wards and community units during a 12
      month study period. METHODS: matched pairs of wards were randomly allocated to
      intervention or control groups. In the intervention wards, staff used a pre
      printed care plan for patients identified as at risk of falling and introduced
      appropriate remedial measures. Numbers of falls in each group were then compared.
      RESULTS: after introduction of the care plan there was a significant reduction in
      the relative risk of recorded falls on intervention wards (relative risk 0.79,
      95% CI 0.65-0.95) but not on control wards (RR 1.12, 95% CI 0.96-1.31). The
      difference in change between the intervention wards and control wards was highly
      significant (RR 0.71, 95% CI 0.55-0.90, P = 0.006). There was no significant
      reduction in the incidence of falls-related injuries. CONCLUSION: the use of a
      core care plan targeting risk factor reduction in older hospital in-patients was
      associated with a reduction in the relative risk of recorded falls.

PMID- 15151916
TI  - Dual effect of insulin-like growth factor on the apical 70-pS K channel in the
      thick ascending limb of rat kidney.
AB  - We used the patch-clamp technique to study the effect of insulin-like growth
      factor I (IGF-I) on the apical 70-pS K channel in the isolated thick ascending
      limb (TAL) of the rat kidney. The isolated TAL was cut open to gain access to the
      apical membrane. Addition of 25 nM IGF-I stimulates the apical 70-pS K channel
      and increases channel activity, defined by the product of channel open
      probability and channel number, from 0.31 to 1.21. The stimulatory effect of IGF
      I is not mediated by nitric oxide- or protein tyrosine phosphatase-dependent
      mechanisms, because inhibition of nitric oxide synthase or blocking protein
      tyrosine phosphatase did not abolish the stimulatory effect of IGF-I on the 70-pS
      K channel. In contrast, inhibition of mitogen-activated protein (MAP) kinase with
      PD-98059 or U0126 abolished the stimulatory effect of IGF-I. This suggests that
      MAP kinase is responsible for mediating the effect of IGF-I on the apical K
      channels. Moreover, the effect of IGF-I on the apical 70-pS K channel is biphasic
      because high concentrations (>200 nM) inhibit apical 70-pS K channels.
      Application of 400 nM IGF-I decreased channel activity from 1.45 to 0.2. The
      inhibitory effect of IGF-I is not blocked by calphostin C (an inhibitor of PKC),
      but inhibition of protein tyrosine kinase with herbimycin A abolished the IGF
      induced inhibition. We conclude that IGF-I has a dual effect on the apical 70-pS
      K channel in the TAL: low concentrations of IGF-I stimulate, whereas high
      concentrations inhibit the channel activity. The stimulatory effect of IGF-I is
      mediated by a MAP kinase-dependent pathway, whereas the inhibitory effect is the
      result of stimulation of protein tyrosine kinase.

PMID- 15151917
TI  - Channel-forming peptide modulates transepithelial electrical conductance and
      solute permeability.
AB  - NC-1059, a synthetic channel-forming peptide, transiently increases
      transepithelial electrical conductance (g(TE)) and ion transport (as indicated by
      short-circuit current) across Madin-Darby canine kidney (MDCK) cell monolayers in
      a time- and concentration-dependent manner when apically exposed. g(TE) increases
      from <2 to >40 mS/cm(2) over the low to middle micromolar range. Dextran polymer
      (9.5 but not 77 kDa) permeates the monolayer following apical NC-1059 exposure,
      suggesting that modulation of the paracellular pathway accounts for changes in
      g(TE). However, concomitant alterations in junctional protein localization
      (zonula occludens-1, occludin) and cellular morphology are not observed. Effects
      of NC-1059 on MDCK g(TE) occur in nominally Cl(-)- and Na(+)-free apical media,
      indicating that permeation by these ions is not required for effects on g(TE),
      although two-electrode voltage-clamp assays with Xenopus oocytes suggest that
      both Cl(-) and Na(+) permeate NC-1059 channels with a modest Cl(-)
      permselectivity (P(Cl):P(Na) = 1.3). MDCK monolayers can be exposed to multiple
      NC-1059 treatments over days to weeks without diminution of response, alteration
      in the time course, or loss of responsiveness to physiological and
      pharmacological secretagogues. Together, these results suggest that NC-1059
      represents a valuable tool to investigate tight junction regulation and may be a
      lead compound for therapeutic interventions.

PMID- 15151919
TI  - Increased levels of hypoxia-sensitive proteins in allergic airway inflammation.
AB  - In this study we investigated the alterations in protein levels that are induced
      by allergic eosinophilic lung inflammation. Lung tissue eosinophilia and
      sequestration of inflammatory cells in airspaces were provoked by systemic
      sensitization with ovalbumin followed by repeated inhalation challenge with
      aerosolized ovalbumin. Proteome alterations in lung tissue and bronchoalveolar
      lavage fluid, respectively, were examined by two-dimensional gel electrophoresis
      followed by identification of proteins by mass spectrometry. Several proteins
      were markedly increased in inflamed tissue. In particular, several proteins that
      are known to be associated with hypoxia were elevated, for example, glycolytic
      enzymes, glucose-regulated protein 78 kD, prolyl-4-hydroxylase, peroxiredoxin 1,
      and arginase. Out of the identified proteins, Ym2 displayed the clearest
      increase, present at high levels in animals with lung eosinophilia, while being
      undetectable in control subjects. Furthermore, the levels of cathepsin S were
      markedly increased in inflamed tissue. Taken together, this study identifies a
      number of marker proteins associated with the pathogenesis of allergic lung
      inflammation and indicates a link between allergic airway inflammation and
      induction of hypoxia-related gene products.

PMID- 15151920
TI  - Abnormal alveolar attachments with decreased elastic fiber content in distal lung
      in fatal asthma.
AB  - Small airway disease is thought to contribute significantly to functional
      impairment caused by asthma. Functional evidence of airway-parenchyma uncoupling
      in asthma, such as loss of deep breath bronchodilator effect in
      bronchoconstrictive episodes and enhanced airway closure, has been previously
      demonstrated. Elastic fibers are essential to maintain adequate elastic recoil of
      the lungs. In this study, we hypothesized that alveolar attachments could be
      abnormal and that elastic fibers could be damaged in the distal lungs of patients
      with fatal asthma. For this purpose, we measured the number of abnormal alveolar
      attachments and quantified the content of elastic fibers in the adventitial layer
      of small airways and in the peribronchial and distal alveolar septa of 15
      patients who died of asthma (FA) and 9 control subjects (CTRL). Our data
      (geometric mean [range]) showed an increased proportion of abnormal alveolar
      attachments per centimeter of basement membrane perimeter in fatal asthma (FA,
      0.18 [0.03-4.00]; CTRL, 0.00 [0.00-0.12]; p < 0.001) and decreased elastic fiber
      content in the small airway adventitial layer (FA, 4.08 [2.22-11.46] microm;
      CTRL, 6.79 [5.62-10.0] microm; p = 0.01) and in the peribronchial alveoli (FA,
      1.08 [0.46-1.91] microm; CTRL, 1.81 [1.22-1.74] microm; p = 0.003), but not in
      the distal alveoli. We propose that structural alterations at the peribronchiolar
      level might contribute to the pathogenesis of some functional abnormalities
      observed in patients with severe asthma.

PMID- 15151918
TI  - Subacute hypoxia decreases voltage-activated potassium channel expression and
      function in pulmonary artery myocytes.
AB  - Chronic hypoxia results in both structural changes in the pulmonary artery and a
      sustained increase in pulmonary vascular tone. This study investigated the
      effects of subacute moderate hypoxia on expression and function of potassium (K+)
      channels in rat pulmonary artery myocytes (PASMCs). The rats were kept at 0.67
      atmospheres for 6, 12, or 24 h. We found that the expression of mRNA for voltage
      activated K+ channels (Kv)1.2, Kv1.5, and Kv2.1 is reduced after less than 24 h
      of this moderate hypoxia. K+ current (Ik) is significantly inhibited in PASMCs
      from rats hypoxic for 24 h, resting membrane potential is depolarized and
      cytosolic [Ca2+] is increased in these cells. In addition, antibodies to Kv1.2,
      Kv1.5, and Kv2.1 inhibit Ik, cause membrane depolarization and attenuate both
      hypoxia- and 4-AP-induced elevation in [Ca2+]i in PASMCs from normoxic rats but
      not from 24 h hypoxic rats. Subacute hypoxia does not completely remove the mRNA
      for Kv1.2, Kv1.5, and Kv2.1, but antibodies against these channels no longer
      alter Ik or cytosolic calcium, suggesting that subacute hypoxia may inactivate
      the channels as well as reduce expression. As the expression of mRNA for Kv1.2,
      Kv1.5, and Kv2.1 is sensitive to subacute hypoxia and decreased
      expression/function of these channels has physiologic effects on membrane
      potential and cytosolic calcium, it seems likely that these Kv channels may also
      be involved in the mechanism of high-altitude pulmonary edema and possibly in the
      signaling of chronic hypoxic pulmonary hypertension.

PMID- 15151921
TI  - Positive clinical trials: understand the control group before implementing the
      result.

PMID- 15151923
TI  - Higher prostaglandin e2 production by dendritic cells from subjects with asthma
      compared with normal subjects.
AB  - Dendritic cells (DCs) are thought to play an important role in the pathogenesis
      of allergic disorders through their ability to interact with T cells to initiate
      and amplify helper T cell Type 2 immune responses. The mechanisms by which this
      occurs are not completely understood, nor is it clear whether DC function differs
      between normal individuals and individuals with asthma. We compared the function
      of DCs from 10 subjects with allergic asthma and 10 normal individuals, focusing
      on the production of prostaglandin E (PGE) 2, interleukin (IL)-10, and IL-12 p70,
      mediators that play an important role in helper T cell Type 1/Type 2
      polarization. Monocyte-derived DCs were established by culturing monocytes with
      granulocyte-macrophage colony-stimulating factor and IL-4 for 7 days, and then
      stimulated with LPS plus IFN-gamma. PGE2, IL-10, and IL-12 production was
      evaluated by ELISA, whereas cyclooxygenase-1, and -2 messenger RNA expression was
      analyzed using reverse transcription-polymerase chain reaction. LPS-stimulated
      monocyte-derived DCs from individuals with asthma exhibited increased PGE2 and IL
      10 production, but equivalent IL-12 p70 synthesis, when compared with DCs from
      normal subjects. Increased PGE2 synthesis by DCs from subjects with asthma was
      associated with an increase in cyclooxygenase-2 messenger RNA expression. These
      findings support the notion that DC function is significantly altered in allergic
      asthma.

PMID- 15151924
TI  - Ovarian aging in two species of long-lived rockfish, Sebastes aleutianus and S.
      alutus.
AB  - Little is known about the ovary during aging in long-lived fish with respect to
      follicular stages and de novo oogenesis. We examined two species of rockfish,
      Sebastes aleutianus (rougheye rockfish) and Sebastes alutus (Pacific ocean
      perch). Fish were sampled offshore of British Columbia, age was estimated by
      otolith annuli, and the ovaries were examined histologically. In S. aleutianus,
      age up to 80 yr did not markedly alter the frequency distribution of oocytes,
      follicles, or their total numbers. Similarly, in a larger sample of S. alutus,
      the abundance of oocytes and follicles showed little age trend up through 77 yr.
      However, fish older than 50 yr lacked the largest and smallest oocyte size
      classes (40-60, >80 microm) and the smallest follicle size class (200-350
      microm), which results from the later seasonal developmental state of these older
      fish. These data provide evidence that oogenesis continues at advanced ages in
      these two species, in contrast with long-held assumptions about mammals. These
      species represent an iteroparous extreme in the spectrum of life history
      strategies and merit investigation to determine the mechanisms for such an
      extended reproductive life span.

PMID- 15151925
TI  - Decrease of fertilizing ability of mouse spermatozoa after freezing and thawing
      is related to cellular injury.
AB  - In general, the fertilizing ability of cryopreserved mouse spermatozoa is less
      than that of fresh spermatozoa. This ability is especially low in C57BL/6, the
      main strain used for the production of transgenic mice. To solve this problem,
      the relationship between cell damage and fertilizing ability in cryopreserved
      mouse spermatozoa was examined in this study. Sperm motility analysis revealed no
      significant difference among the motilities of cryopreserved C57BL/6J, BALB/cA,
      and DBA/2N sperm (67.6%, 43.4%, and 60.0%, respectively) after thawing. However,
      the results of in vitro fertilization (IVF), scanning electron microscopy (SEM),
      and transmission electron microscopy (TEM) showed a strong correlation between
      the frequency of aberrant spermatozoa (FAS) and fertilization rates (FR;
      C57BL/6J: FAS, 83.7%; FR, 17.0%; BALB/cA: FAS, 67.2%; FR, 24.2%; and DBA/2N: FAS,
      10.2%; FR, 93.6%), and damage to spermatozoa was localized particularly in the
      acrosome of the head and mitochondria.

PMID- 15151922
TI  - Upper airway muscle inflammation and denervation changes in obstructive sleep
      apnea.
AB  - Inflammatory cell infiltration and afferent neuropathy have been shown in the
      upper airway (UA) mucosa of subjects with obstructive sleep apnea (OSA). We
      hypothesized that inflammatory and denervation changes also involve the muscular
      layer of the pharynx in OSA. Morphometric analysis was performed on UA tissue
      from nonsnoring control subjects (n = 7) and patients with OSA (n = 11) following
      palatal surgery. As compared with control subjects, inflammatory cells were
      increased in the muscular layer of patients with OSA, with CD4+ and activated
      CD25+ T cells (both increased approximately threefold) predominating.
      Inflammation was also present in UA mucosa, but with a different pattern
      consisting of CD8+ (2.8-fold increase) and activated CD25+ (3.2-fold increase) T
      cell predominance. As ascertained by immunoreactivity for the panneuronal marker
      PGP9.5, there was a dramatic (5.7-fold) increase in intramuscular nerve fibers in
      OSA patients compared with control subjects, as well as direct evidence of
      denervation based on positive immunostaining of the muscle fiber sarcolemmal
      membrane for the neural cell adhesion molecule in patients with OSA. These data
      suggest that inflammatory cell infiltration and denervation changes affect not
      only the mucosa, but also the UA muscle of patients with OSA. This may have
      important implications for the ability to generate adequate muscular dilating
      forces during sleep.

PMID- 15151926
TI  - Seasonal expression of INSL3 and Lgr8/Insl3 receptor transcripts indicates
      variable differentiation of Leydig cells in the roe deer testis.
AB  - Roe deer are seasonal breeders and show cyclic variation in testicular volume and
      cellular differentiation within the tubular and interstitial testis compartment.
      We have employed the roe deer as a model to elucidate the expression of the
      postpubertal Leydig cell marker INSL3 during seasonal changes in Leydig cell
      differentiation. Roe deer testis and serum samples were collected bimonthly
      throughout the complete reproductive cycle. Peak levels of testicular Insl3 mRNA
      and INSL3 immunoprotein were detected well before the onset of rut in April and
      coincided with the highest percentage of INSL3-positive cell number/square
      millimeter of testicular interstitial area. During the winter (December,
      February), roe deer INSL3 was exclusively detected in a subpopulation of alpha
      actin-negative, spindle-shaped peritubular cells. Concordant with the increase in
      INSL3 production in April and 1 mo after the reported LH peak, a sharp increase
      in serum testosterone concentrations was observed. High serum testosterone
      concentrations coincided with the presence of detectable 17alpha-hydroxylase,
      mRNA and protein, in Leydig cells. Upregulation of INSL3 production in spring
      appeared to reflect LH-dependent differentiation of Leydig cells. The
      considerable changes in percentage of INSL3 immunopositive cells within the
      numerically constant interstitial cell population indicated cyclic seasonal de-
      and redifferentiation of Leydig cells. A complex functional role of the
      INSL3/LGR8 ligand-receptor system in the roe deer testis was suggested by the
      detection of specific hybridization signals for roe deer Lgr8 transcripts in
      Sertoli cells of the roe deer testis.

PMID- 15151927
TI  - Role of messenger RNA expression of platelet activating factor and its receptor
      in porcine in vitro-fertilized and cloned embryo development.
AB  - Platelet activating factor (PAF) is known as an autocrine growth/survival factor
      in mammalian preimplantation embryos. This study investigated the expression of
      porcine PAF receptor (PAFr) mRNA and its role in porcine in vitro fertilized
      (IVF) or somatic cell nuclear transfer (SCNT) embryo development. The expression
      of PAFr mRNA in IVF or SCNT blastocysts was shown by reverse transcription
      polymerase chain reaction (RT-PCR) and Southern blot analysis. Semiquantitative
      RT-PCR and Southern blot analysis demonstrated that PAFr mRNA was expressed
      during preimplantation embryo development, it was highly expressed through the 2
      cell to 8-cell embryo stage, and it decreased at the morula stage. PAFr mRNA
      expression was detected steadily in IVF embryos, whereas it was varied at the 2
      cell, 4-cell, and blastocyst stages in SCNT embryos. To determine the role of PAF
      in IVF and SCNT embryo development, embryos were cultured in North Carolina State
      University (NCSU)-23 medium supplemented with different concentrations of PAF (0,
      0.037, 0.37, 3.72, or 37.2 nM). The PAF supplement significantly increased the
      rate of blastocyst formation in SCNT embryos, but not in IVF embryos. The PAF
      supplement for the entire 168 h of culture showed significantly higher blastocyst
      formation in SCNT embryos. Upregulation of PAFr mRNA by PAF in SCNT embryos
      indicated that the embryotrophic effect of PAF was mediated through its
      functional receptors in SCNT embryos. In conclusion, the present study
      demonstrated that PAFr mRNA was expressed in porcine IVF and SCNT embryos, and
      that PAF supplement improved the developmental competence of SCNT embryos through
      its specific receptors.

PMID- 15151929
TI  - Tyrosine phosphorylation, thiol status, and protein tyrosine phosphatase in rat
      epididymal spermatozoa.
AB  - Sperm thiol oxidation and the ability to undergo protein tyrosine phosphorylation
      are associated with the acquisition of sperm motility and fertilizing ability
      during passage of spermatozoa through the epididymis. Phosphotyrosine levels in
      various cells are controlled by tyrosine kinase versus phosphatase, with the
      latter known to be inhibited by oxidation. In the present paper we examine
      whether changes in thiol status during sperm maturation affect rat sperm protein
      phosphotyrosine levels and protein phosphotyrosine phosphatase (PTP) activity.
      Tyrosine phosphorylation, as demonstrated by immunoblotting (IB), was
      significantly increased in several sperm tail proteins during maturation in the
      epididymis. Sperm thiol oxidation with diamide enhanced tail protein
      phosphorylation; reduction of disulfides with dithiothreitol diminished
      phosphorylation. In the sperm head, a moderate increase in tyrosine
      phosphorylation was accompanied by altered localization of phosphotyrosine
      proteins during maturation. Blocking of thiols and PTP activity with N
      ethylmaleimide led to increased tyrosine phosphorylation of protamine in caput
      sperm heads. Several PTP bands were identified by IB. In the caput spermatozoa, a
      prominent level of the 50 kDa band was present, whereas in the cauda spermatozoa
      a very low level of the 50 kDa band was found. PTP activity, measured by using p
      nitrophenyl phosphate as a substrate, was significantly higher in the caput
      spermatozoa (high thiol content) than in the cauda spermatozoa (low thiol
      content). Our results show that PTP activity is correlated with sperm thiol
      status and suggest that tyrosine phosphorylation of sperm proteins during sperm
      maturation is promoted by thiol oxidation and diminished PTP.

PMID- 15151928
TI  - Postthaw evaluation of in vitro function of epididymal spermatozoa from four
      species of free-ranging African bovids.
AB  - An improved understanding of reproductive physiology in nondomestic bovids is
      necessary for the development of assisted reproductive technologies (ARTs) for
      use in the conservation of endangered bovids. In this study, epididymal
      spermatozoa were recovered from blesbok (Damaliscus dorcas phillipsi), African
      buffalo (Syncerus caffer), springbok (Antidorcas marsupialis), and black
      wildebeest (Connochaetes gnou) following organized culls in South Africa. Our
      objectives were 1) to characterize the quality of epididymal spermatozoa, 2)
      evaluate the effectiveness of a cryopreservation protocol, and 3) compare
      postthaw sperm longevity (motility, viability, and acrosomal integrity) and
      functionality in two culture media with two capacitation reagents (caffeine and
      heparin). Following recovery, spermatozoa were diluted in EQ extender, slow
      cooled, and frozen in the presence of 5% glycerol. Thawed spermatozoa were
      separated on a Percoll gradient and diluted in fertilization media (SOF for
      fertilization [SOFfert]; 0.6% BSA, 0.0 mM glucose, 25.0 mM NaHCO(3)) or modified
      SOFfert (1.2% BSA, 1.5 mM glucose, 37.0 mM NaHCO(3)) and either heparin or
      caffeine, and incubated for 6 h. Spermatozoa from these species maintained an
      average of 64% initial motility after thawing. Incubation medium and capacitation
      reagent had species-specific effects on the motility, viability, and acrosomal
      integrity of spermatozoa, suggesting ART procedures need to be optimized for each
      species. Springbok spermatozoa were also shown to be competent for in vitro
      fertilization. Information from this study concerning sperm physiology in
      blesbok, African buffalo, springbok, and black wildebeest will be useful in the
      development of ART for the conservation of these and other species of bovids.

PMID- 15151930
TI  - Effect of glutathione depletion on antioxidant enzymes in the epididymis, seminal
      vesicles, and liver and on spermatozoa motility in the aging brown Norway rat.
AB  - Reactive oxygen species (ROS) play a role in male infertility, where excessive
      amounts impair spermatozoal motility. Epididymal antioxidant enzymes protect
      spermatozoa from oxidative damage in the epididymal lumen. Antioxidant secretions
      from the seminal vesicle protect spermatozoa after ejaculation. As it is known
      that with age there is increased generation of ROS, the goals of this study were
      to determine how aging affects the response of antioxidant enzymes in the
      epididymis, seminal vesicles, and liver to l-buthionine-S,R-sulfoximine (BSO)
      mediated glutathione (GSH) depletion, and to examine the impact of GSH depletion
      on motility parameters of spermatozoa from the cauda epididymidis in young (4-mo
      old) and old (21-mo-old) rats. Levels of GSH and glutathione disulfide (GSSG), as
      well as activities of glutathione peroxidase, glutathione reductase, catalase,
      and superoxide dismutase, were measured in the caput, corpus and cauda
      epididymidis, seminal vesicles, and liver. Spermatozoal motility was assessed by
      computer-assisted sperm analysis. Significant age-related changes in antioxidant
      enzyme activities were found in the liver and cauda epididymidis. Glutathione
      depletion clearly affected tissues in both young and old. The compounding effect
      of age was most evident in the cauda epididymidis, seminal vesicles, and liver,
      where antioxidant enzyme activities changed significantly. Additionally,
      spermatozoa motility was adversely affected after BSO treatment in both age
      groups, but significantly more so in older animals. In summary, the male
      reproductive tissues and liver undergo age-related changes in antioxidant enzyme
      activities and in their response to GSH depletion.

PMID- 15151931
TI  - Selective passage through the uterotubal junction of sperm from a mixed
      population produced by chimeras of calmegin-knockout and wild-type male mice.
AB  - Loss of calmegin, a testis-specific putative chaperone protein of the endoplasmic
      reticulum, leads to male sterility because the sperm show defects in migration
      into the oviduct and do not bind to the zona pellucida. To clarify the mechanism
      of defective migration, XY <--> XY chimeras were produced by aggregating wild
      type embryos with embryos of transgenic mice lacking functional calmegin genes
      and expressing enhanced green fluorescent protein (EGFP) in their acrosomes.
      Chimeric ejaculates contained wild-type, nonfluorescent sperm as well as sperm
      with EGFP-tagged acrosomes and the defective calmegin gene. Transgenic, wild
      type, and chimeric males were mated to wild-type females; however, only wild-type
      sperm were ever found within the oviducts. Calmegin-knockout sperm, even when
      they were combined in chimeric ejaculates with wild-type sperm, remained outside
      of the uterotubal junction. These findings indicate that the presence of wild
      type sperm cannot compensate for the inability of calmegin-knockout sperm to
      enter the oviduct and that successful ascent into the oviduct depends on the
      capabilities of individual sperm.

PMID- 15151932
TI  - Biological activity of cryopreserved bovine spermatogonial stem cells during in
      vitro culture.
AB  - Functional roles of spermatogonial stem cells in spermatogenesis are self
      renewing proliferation and production of differentiated daughter progeny. The
      ability to recapitulate these actions in vitro is important for investigating
      their biology and inducing genetic modification that could potentially lead to an
      alternative means of generating transgenic animals. The objective of this study
      was to evaluate the survival and proliferation of frozen-thawed bovine
      spermatogonial stem cells in vitro and investigate the effects of exogenous glial
      cell line-derived neurotrophic factor (GDNF). In order to accomplish this
      objective we developed a bovine embryonic fibroblast feeder cell line, termed
      BEF, to serve as feeder cells in a coculture system with bovine germ cells.
      Bovine spermatogonial stem cell survival and proliferation in vitro were
      evaluated by xenogeneic transplantation into the seminiferous tubules of
      immunodeficient mice. Bovine germ cells cocultured for 1 wk resulted in
      significantly more round cell donor colonies in recipient mouse testes compared
      to donor cells transplanted just after thawing. Bovine germ cells cocultured for
      2 wk had fewer colony-forming cells than the freshly thawed cell suspensions or
      cells cultured for 1 wk. Characterization of the feeder cell line revealed
      endogenous expression of Gdnf mRNA and protein. Addition of exogenous GDNF to the
      culture medium decreased the number of stem cells present at 1 wk of coculture,
      but enhanced stem cell maintenance at 2 wk compared to cultures without added
      GDNF. These data indicate that frozen-thawed bovine spermatogonial stem cells
      survive cryopreservation and can be maintained during coculture with a feeder
      cell line in which the maintenance is influenced by GDNF.

PMID- 15151934
TI  - Cdc2-cyclin B-induced G2 to M transition in perch oocyte is dependent on Cdc25.
AB  - The G2 to M phase transition in perch oocytes is regulated by maturation
      promoting factor (MPF), a complex of Cdc2 and cyclin B. In Anabas testudineus, a
      fresh water perch, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, the maturation
      inducing hormone (MIH), induced complete germinal vesicle breakdown (GVBD) of
      oocytes at 21 h. An unusual cyclin, p30 cyclin B, has been identified in oocyte
      extract using both monoclonal and polyclonal antibodies. Surprisingly, Cdc2 could
      not be identified, although a Northern blot with Cdc2 cDNA demonstrated
      expression of the gene. Purification of MPF through an immunoaffinity column
      followed by SDS-PAGE showed three proteins, Cdc2, cyclin B, and a 20 kDa
      fragment, indicating earlier failure in immunodetection may be due to the
      interference by this fragment. In uninduced oocytes, p30 cyclin B was present,
      and its expression was increased by MIH. MIH increased p30 cyclin B accumulation
      at 3 h, a high level which was maintained between 9 and 21 h, but an effective
      increase in GVBD and H1 kinase activation could only be observed between 15 and
      21 h. This delay in active MPF formation was found to be related to the
      activation of Cdc25, phosphorylation of which was detected at 12 h, and a
      substantial increase occurred during 15-18 h. Sodium orthovanadate, a tyrosine
      phosphatase inhibitor, inhibited H1 kinase activity and GVBD, suggesting the
      requirement of Cdc25 activity in MPF activation. Our results show occurrence of
      pre-MPF in uninduced oocytes and its conversion to active MPF requires
      dephosphorylation by Cdc25, the existence of which has not yet been shown in
      fish.

PMID- 15151933
TI  - Estrogenicity of the isoflavone metabolite equol on reproductive and non
      reproductive organs in mice.
AB  - Equol, a metabolite of the phytoestrogen daidzein, is present at significant
      levels in some humans who consume soy and in rodents fed soy-based diets. Equol
      is estrogenic in vitro, but there have been limited studies of its activity in
      vivo. We evaluated equol effects on reproductive and non-reproductive endpoints
      in mice. Ovariectomized age-matched (30-day-old) female C57BL/6 mice were fed
      phytoestrogen-free diets and given a racemic mixture of equol by daily injections
      (0, 4, 8, 12, or 20 mg [kg body weight](-1) day(-1)) or in the diet (0, 500, or
      1,000 ppm) for 12 days. Mice were killed, and serum concentrations of total and
      aglycone equol were measured. Total serum equol concentrations ranged from 1.4 to
      7.5 microM with increasing doses of injected equol, but uterine weight increased
      significantly only at 12 and 20 mg (kg body weight)(-1) day(-1). Dietary equol at
      500 or 1,000 ppm produced total serum equol concentrations of 5.9 and 8.1 microM,
      respectively, comparable with those in rodents consuming certain high-soy chows;
      the proportion of equol present as the free aglycone was much lower with dietary
      administration than injections, which may be a factor in the greater biological
      effects induced by injections. Dietary equol did not significantly increase
      uterine weight. Increasing dietary and injected equol doses caused a dose
      dependent increase in vaginal epithelial thickness. Uterine epithelial
      proliferation was increased by equol injections at 8-20 mg (kg body weight)(-1)
      day(-1) and 1,000 ppm dietary equol. Neither dietary nor injected equol decreased
      thymic or adipose weights. In conclusion, equol is a weak estrogen with modest
      effects on endpoints regulated by estrogen receptor alpha when present at serum
      levels seen in rodents fed soy-based diets, but quantities present in humans may
      not be sufficient to induce estrogenic effects, although additive effects of
      equol with other phytoestrogens may occur.

PMID- 15151935
TI  - Prior experience with photostimulation enhances photo-induced reproductive
      development in female European starlings: a possible basis for the age-related
      increase in avian reproductive performance.
AB  - Reproductive performance in female birds improves with age, and this is generally
      attributed to experiences obtained during breeding. In temperate-zone species,
      experience with photostimulation during the first breeding year may prime the
      hypothalamo-pituitary-gonadal axis to respond to photic cues more rapidly or
      robustly in subsequent years. To test this idea, we captured 32 photorefractory
      juvenile (hence naive to photostimulation) female European starlings (Sturnus
      vulgaris) and held half of them (naive group) on a photoperiod of 8L:16D for 32
      wk and the other half (experienced group) on 8L:16D for 12 wk, 16L:8D for 12 wk,
      and then 8L:16D for 8 wk. When we subsequently transferred all birds to 16L:8D,
      the increase in body mass, which may presage egg laying in the wild, was more
      robust in experienced than in naive females. Experienced females also showed a
      more robust elevation in plasma concentrations of the yolk-precursor protein
      vitellogenin, although naive females showed an initial rapid but transient rise
      in vitellogenin that we attribute to their extended exposure to short-day
      photoperiods prior to photostimulation. Finally, the photo-induced increase in
      diameter of the largest ovarian follicle, in plasma concentrations of luteinizing
      hormone, and in the number of septo-preoptic fibers relative to the number of
      cell bodies immunoreactive to GnRH was greater in experienced than in naive
      females. Thus, prior experience with photostimulation enhances some initial
      phases of photo-induced reproductive development and may explain, in part, why
      reproductive performance improves with age in temperate-zone birds.

PMID- 15151936
TI  - A short core promoter drives expression of the ALF transcription factor in
      reproductive tissues of male and female mice.
AB  - The control of gene expression in reproductive tissues involves a number of
      unique germ cell-specific transcription factors. One such factor, ALF (TFIIA
      tau), encodes a protein similar to the large subunit of general transcription
      factor TFIIA. To understand how this factor is regulated, we characterized
      transgenic mice that contain the ALF promoter linked to either beta-galactosidase
      or green fluorescent protein (GFP) reporters. The results show that as little as
      133 base pairs are sufficient to drive developmentally accurate and cell-specific
      expression. Transgene DNA was methylated and inactive in liver, but could be
      reactivated in vivo by system administration of 5-aza, 2'-deoxycytidine.
      Fluorescence-activated cell sorting allowed the identification of male germ cells
      that express the GFP transgene and provides a potential method to collect cells
      that might be under the control of a nonsomatic transcription system. Finally, we
      found that transcripts from the endogenous ALF gene and derived transgenes can
      also be detected in whole ovary and in germinal vesicle-stage oocytes of female
      mice. The ALF sequence falls into a class of germ cell promoters whose features
      include small size, high GC content, numerous CpG dinucleotides, and an apparent
      TATA-like element. Overall, the results define a unique core promoter that is
      active in both male and female reproductive tissues, and suggest mouse ALF may
      have a regulatory role in male and female gametogenic gene expression programs.

PMID- 15151938
TI  - Obesity and breast cancer prognosis: an expanding body of evidence.

PMID- 15151937
TI  - Self-testing for human papillomavirus using a vaginal swab: placing prevention of
      cervical cancer in the patient's hands.

PMID- 15151939
TI  - CD40 activation: potential for specific immunotherapy in B-CLL.
AB  - Despite encouraging scientific and therapeutic advances, chronic lymphocytic
      leukemia (CLL) principally remains an incurable disease. Allogeneic
      transplantation represents the only curative approach, but is marked by high
      mortality. Novel and less toxic treatment modalities are needed.
      Immunotherapeutic approaches have clearly demonstrated potential effectiveness in
      CLL and other B-cell malignancies. To successfully direct immunity against CLL,
      highly immunogenic tumor cells or tumor-antigen-loaded antigen-presenting cells
      are necessary. The CD40-CD40L interaction has been shown to significantly
      increase antigen presentation in normal and malignant B-cells. Here we discuss
      biology and potential therapeutic applications of the CD40-system in CLL.

PMID- 15151940
TI  - Extravasation of systemic hemato-oncological therapies.
AB  - Systemic intravenous chemotherapeutic agents can cause multiple emergency
      situations including acute and chronic local and systemic reactions. Amongst
      them, drug extravasation is one of the most devastating complications, as many
      drugs can cause varying degrees of local tissue injury when extravasated.
      Although it is difficult to give an accurate measurement, the incidence of
      extravasation of systemic infusional chemotherapeutic agents has been reported to
      occur in 0.1-6.5% of cases. Since most extravasations can be prevented with the
      systematic implementation of careful administration techniques, guidelines have
      been published for the administration of vesicant drugs. The proper maintenance
      of intravenous lines, application of local cooling or warming for certain
      extravasations, and the use of antidotes to prevent the local toxic action of the
      extravasated drugs are the basis of medical management. The specific antidotes
      for certain chemotherapeutic agents are also discussed in this article.

PMID- 15151941
TI  - Primary cervical cancer screening by self-sampling of human papillomavirus DNA in
      internal medicine outpatient clinics.
AB  - BACKGROUND: We determined whether testing of self-collected vaginal swabs for
      human papillomavirus (HPV) DNA can be used to screen for cervical disease within
      internal medicine outpatient clinics. PATIENTS AND METHODS: In this prospective
      study, 560 patients visiting two referral outpatient clinics for internal
      medicine were asked to take an HPV self-sample. Acceptability of self sampling,
      HPV prevalence and cervical intraepithelial neoplasia (CIN) detection rate were
      evaluated. RESULTS: 435 women (78%) performed HPV self-sampling; 1.5% considered
      self-sampling to be difficult. 134 women (31%) tested positive for high-risk type
      of HPV. There were significant differences between HPV-positive and -negative
      women with respect to the following: mean age (42 versus 46 years), number of
      women aged <16 years at first coitus (35% versus 23%) and history of drug abuse
      (8.3% versus 2.6%). Colposcopy could be performed for 70 HPV positive women: CIN
      1-3 was identified in 24%. Two of 52 women with HPV-negative results undergoing
      colposcopy had biopsy-confirmed CIN 1. Test performance for detection of CIN 2-3
      after correction for verification bias: sensitivity, 100%; specificity, 71%;
      negative predictive value, 100%; positive predictive value, 10%. HPV persistence
      was associated with a 5.7-fold risk of CIN 2-3 detection at follow-up.
      CONCLUSIONS: Self-assessment for HPV DNA is an easy, feasible and well-accepted
      method for HPV testing and for cervical cancer screening in internal medicine
      outpatient clinics.

PMID- 15151942
TI  - Histopathological validation of the sentinel node concept in cervical cancer.
AB  - BACKGROUND: The sentinel node (SN) is defined as the first node in the lymphatic
      system that drains a tumor site. If the SN is not metastatic, then all other
      nodes should also be disease-free. We used serial sections and
      immunohistochemical (IHC) staining to examine both sentinel and non-sentinel
      nodes (non-SNs). MATERIALS AND METHODS: From July 2001 to March 2003, 18 patients
      (median age, 48 years) with cervical cancer (stage IA2, one patient; stage IB1,
      nine patients; stage IB2, three patients; stage IIA, three patients; and stage
      IIB, two patients) underwent a laparoscopic SN procedure based on a combined
      detection method, followed by complete laparoscopic pelvic lymphadenectomy. If
      the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC
      staining, all non-SNs were also examined by the combined staining method.
      RESULTS: A mean of 2.4 SNs (range 1-5) and 8 non-SNs (range 4-14) were excised
      per patient. Eight SNs (18.2%) from five patients (27.8%) were found to be
      metastatic at the final histological assessment, including two macrometastatic
      SNs, three micrometastatic SNs and isolated tumor cells in three SNs. In 13
      patients, no metastatic SN involvement was detected by H&E and IHC staining. In
      these 13 patients, 106 non-SNs were examined by serial sectioning and IHC, and
      none was found to be metastatic. CONCLUSIONS: The SN procedure appears to
      reliably predict the metastatic status of the regional lymphatic basin in
      patients with cervical cancer.

PMID- 15151943
TI  - Body mass index as a prognostic feature in operable breast cancer: the
      International Breast Cancer Study Group experience.
AB  - BACKGROUND: Current information on the prognostic importance of body mass index
      (BMI) for patients with early breast cancer is based on a variety of equivocal
      reports. Few have data on BMI in relationship to systemic treatment. PATIENTS AND
      METHODS: Patients (6792) were randomized to International Breast Cancer Study
      Group trials from 1978 to 1993, studying chemotherapy and endocrine therapy. BMI
      was evaluated with eight other factors: menopausal status, nodal status, estrogen
      receptor status, progesterone receptor status, tumor size, vessel invasion, tumor
      grade and treatment. BMI was categorized as normal (< or =24.9), intermediate
      (25.0-29.9) or obese (> or =30.0). RESULTS: Patients with normal BMI had
      significantly longer overall survival (OS) and disease-free survival (DFS) than
      patients with intermediate or obese BMI in pairwise comparisons adjusted for
      other factors. Subset analyses showed the same effect in pre- and perimenopausal
      patients and in those receiving chemotherapy alone. When assessed globally and
      adjusted for other factors, BMI significantly influenced OS (P = 0.03) but not
      DFS (P = 0.12). CONCLUSIONS: BMI is an independent prognostic factor for OS in
      patients with breast cancer, especially among pre-/perimenopausal patients
      treated with chemotherapy without endocrine therapy.

PMID- 15151944
TI  - NF-kappa B inhibition markedly enhances sensitivity of resistant breast cancer
      tumor cells to tamoxifen.
AB  - Studies show that high Akt activity in breast carcinoma is associated with
      endocrine therapy resistance. Breast cancer cell lines expressing a
      constitutively active Akt are able to proliferate under reduced estrogen
      conditions, and are resistant to the growth inhibitory effects of tamoxifen.
      Understanding the targets of Akt signaling mediating tamoxifen resistance is of
      clinical significance. One possible target is nuclear factor kappa B (NF-kappa
      B), a transcription factor that plays a critical role in resistance to apoptosis
      and the induction of angiogenesis and invasion. In the present study, we found
      that Akt activity correlated with phosphorylation of I kappa B (the negative
      regulator of NF-kappa B), NF-kappa B DNA binding and tamoxifen resistance in
      vivo. Importantly, we found that co-treatment with the NF-kappa B inhibitor,
      parthenolide, or overexpression of I kappa B superrepressor restored tamoxifen
      sensitivity to our refractory Akt MCF-7 cells. These data suggest that activation
      of NF-kappa B via the PI3K/Akt signaling pathway may be a significant mechanism
      for development of endocrine therapy resistance in breast cancer, and that
      inhibition of NF-kappa B may be an effective treatment strategy to limit the
      progression of this disease.

PMID- 15151945
TI  - Phase II study of pegylated liposomal doxorubicin (Caelyx) and docetaxel as first
      line treatment in metastatic breast cancer.
AB  - BACKGROUND: The aim of this study was to determine the activity and safety of
      pegylated liposomal doxorubicin (PLD; Caelyx) and docetaxel combination as first
      line treatment in patients with metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Forty-four patients with a median age of 63 years were treated with PLD
      30 mg/m(2) (day 1) and docetaxel 75 mg/m(2) (day 2) every 3 weeks for six cycles.
      Recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) could be used
      in patients with grade > or =3 neutropenia after the first cycle. RESULTS: Forty
      two of 44 patients were assessable for response. The response rate (RR) was 64.3%
      (95% confidence interval 49.8% to 78.8%). Six patients (14.3%) achieved complete
      response (complete disappearance of all measurable and assessable disease lasting
      at least 4 weeks, no new lesions, no disease-related symptoms), partial response
      was observed in 21 patients (50%) > or =50% decrease of measureable disease
      lasting at least 4 weeks, no progression of assessable disease, no new lesions,
      no disease-related symptoms), eight patients had stable disease and seven
      patients progressive disease. Median disease-free and overall survival were not
      reached, but were in excess of 17 months (range 6-17 months). Twenty of the
      patients had received previous adjuvant chemotherapy (10 with epirubicin
      containing regimen with a median cumulative dose of 400 mg/m(2)). Grade > or =3
      neutropenia occurred in 18.4% and neutropenic fever in 9% of patients. Palmar
      plantar erythrodysesthesia was observed in four patients. Dose reduction was
      necessary in seven patients. Two patients discontinued treatment: one due to
      prolonged grade 3-4 neutropenia and one due to neurotoxicity. No treatment
      related deaths occurred. CONCLUSIONS: The combination of PLD and docetaxel
      achieved high RRs with acceptable toxicity as first-line treatment in MBC.

PMID- 15151946
TI  - Prevalence and course of fatigue in breast cancer patients receiving adjuvant
      chemotherapy.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of fatigue
      and the course of fatigue as a function of chemotherapy in breast cancer patients
      undergoing adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective cohort
      study, a sample of 157 patients with breast cancer were interviewed, using the
      Rotterdam Symptom Checklist and the Multidimensional Fatigue Inventory, at the
      first, third and fifth cycle of adjuvant chemotherapy, as well as 4 and 12 weeks
      after the last cycle of adjuvant chemotherapy. Patients were treated with either
      a doxorubicin-containing schedule, or cyclophosphamide, methotrexate and 5
      fluorouracil (CMF). RESULTS: The courses of general and physical fatigue are to a
      large extent similar. After the last cycle of chemotherapy, the CMF group
      reported a significant increase in fatigue, which was followed by a significant
      reduction. In the doxorubicin group a significant increase in fatigue was only
      seen during the first cycles of chemotherapy. The fatigue experienced at the
      first and the last measurements do not differ significantly. CONCLUSIONS: The
      prevalence of fatigue increased significantly after the start of chemotherapy.
      After chemotherapy treatment the prevalence rate seemed to decline. A different
      impact of chemotherapy on the course of fatigue was found. In the doxorubicin
      group a direct increase in fatigue was found. In the CMF group a moderate direct
      increase occurred, followed by a delayed strong increase. An increase in fatigue
      was associated with a decrease in daily functioning. At all measurement occasions
      fatigue was affected by type of operation, such that women with a mastectomy were
      more fatigued than women that underwent a lumpectomy. Receiving radiotherapy also
      led to an increase in fatigue. With this knowledge breast cancer patients can be
      better informed about what they can expect. Further research should include
      interventions addressing how to reduce or cope with fatigue during as well as
      after receiving adjuvant chemotherapy.

PMID- 15151947
TI  - SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy
      improves quality of life without affecting survival, in patients with advanced
      non-small-cell lung cancer: phase III results.
AB  - BACKGROUND: This open-label, randomised phase III study was designed to further
      investigate the clinical activity and safety of SRL172 (killed Mycobacterium
      vaccae suspension) with chemotherapy in the treatment of non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Patients were randomised to receive
      platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin,
      vinblastine and cisplatin or carboplatin) with (210 patients) or without (209
      patients) monthly SRL172. RESULTS: There was no statistical difference between
      the two groups in overall survival (primary efficacy end point) over the course
      of the study (median overall survival of 223 days versus 225 days; P = 0.65).
      However, a higher proportion of patients were alive at the end of the 15-week
      treatment phase in the chemotherapy plus SRL172 group (90%), than in the
      chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase,
      the response rate was 37% in the combined group and 33% in the chemotherapy alone
      group. Patients in the chemotherapy alone group had greater deterioration in
      their Global Health Status score (-14.3) than patients in the chemotherapy plus
      SRL172 group (-6.6) (P = 0.02). CONCLUSION: In this non-placebo controlled trial,
      SRL172 when added to standard cancer chemotherapy significantly improved patient
      quality of life without affecting overall survival times.

PMID- 15151948
TI  - A phase II study of oxaliplatin and paclitaxel in patients with advanced non
      small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin and paclitaxel as
      first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: The treatment regimen was given as defined in a phase I
      investigation in patients with previously treated ovarian cancer. It consisted of
      paclitaxel 175 mg/m(2) (1-h infusion) and oxaliplatin 130 mg/m(2) (2-h infusion)
      given every 21 days. Eligible patients had stage IIIB (pleural effusion)/IV
      NSCLC, measurable disease, no prior chemotherapy, Eastern Cooperative Oncology
      Group performance status 0-2, and adequate hematological, renal and hepatic
      function. RESULTS: A total of 38 patients were enrolled with the following
      characteristics: 29% male (n = 11); 71% female (n = 27); median age 64.5 years
      (range 37-78); performance status of 0-1 84% (n = 32); stage IIIB 8% (n = 3);
      stage IV 92% (n = 35). One hundred and eighty-one cycles were administered, with
      a median of four per patient (range one to 12). The overall objective response
      rate for all 38 patients was 34.2% [95% confidence interval (CI) 19.6% to 51.4%].
      This response rate includes 13 patients who met criteria for a partial response.
      No complete responses were observed. Median overall survival time was 9.2 months
      (95% CI 6-12.4) and median progression-free survival time was 4.3 months (95% CI
      2.1-6.5). The 1- and 2-year overall survival rates were 37% and 21%,
      respectively. Hematological toxicity included six patients with grade 4
      neutropenia. Non-hematological toxicity consisted mainly of grades 1 and 2
      neurosensory toxicity. Laryngodysesthesia was observed in two patients following
      oxaliplatin infusion. No grade 4 non-hematological toxicities were encountered.
      CONCLUSION: This regimen is well tolerated, and demonstrates activity in patients
      with advanced NSCLC.

PMID- 15151949
TI  - Vinorelbine alternating oral and intravenous plus carboplatin in advanced non
      small-cell lung cancer: results of a multicentre phase II study.
AB  - BACKGROUND: Vinorelbine and carboplatin are both active agents in the treatment
      of non-small-cell lung cancer (NSCLC). Vinorelbine has recently been developed in
      an oral formulation, which is as active as the intravenous (i.v.) form. PATIENTS
      AND METHODS: Fifty-two chemonaive patients with unresectable localised or
      metastatic NSCLC received i.v. vinorelbine 25 mg/m(2) plus carboplatin (AUC 5) on
      day 1 and oral vinorelbine 60 mg/m(2) on day 8 (or day 15 if neutrophils
      <1500/mm(3)) every 3 weeks in an open-label, multicentre phase II study. RESULTS:
      A total of 224 cycles were given, with the median number per patient of four
      (range one to eight). Eight responses out of 52 enrolled patients were documented
      and validated by an independent panel review, yielding a response rate of 18.2%
      [95% confidence interval (CI) 6.8-29.6%] in the evaluable population. This
      response rate was balanced by a high rate of disease control (78.9% in the
      intention-to treat population and 90.9% in the evaluable population). The median
      progression-free and median survival were 5.1 months (95% CI 4.3-8.1) and 9.3
      months (95% CI 6.8-11.4), respectively. Overall, the safety profile of the
      combination regimen alternating i.v. and oral vinorelbine appeared similar to
      that expected for each individual agent. Some lung cancer-specific items (pain,
      dyspnoea) improved or were stabilised by assessment using the EORTC QLQ-C30 and
      QLQ-LC13 questionnaires. CONCLUSIONS: The combination of carboplatin with an
      alternating regimen of i.v./oral vinorelbine is a well tolerated regimen with a
      low level of toxicity and a low rate of serious adverse events. A high rate of
      disease control (partial response + no change) was achieved. Progression-free
      survival and overall survival fell within the expected range. This regimen is
      convenient and safe for the treatment of patients with locally advanced or
      metastatic NSCLC patients.

PMID- 15151950
TI  - A phase II trial of the epothilone B analog, BMS-247550, in patients with
      previously treated advanced colorectal cancer.
AB  - BACKGROUND: The epothilone B analog, BMS-247550, is a non-taxane microtubulin
      stabilizing agent with preclinical activity in taxane-resistant cell lines and
      phase I activity in colorectal cancer. We conducted a phase II study of single
      agent BMS-247550 in advanced colorectal cancer patients who had disease
      progression following treatment with irinotecan-5-fluorouracil-leucovorin (IFL).
      PATIENTS AND METHODS: Patients were required to have histologically or
      cytologically confirmed advanced or metastatic colorectal cancer; progressed on
      or after chemotherapy with IFL; Eastern Cooperative Oncology Group performance
      status < or =1; peripheral neuropathy grade < or =1; and adequate laboratory
      parameters. BMS-247550 40 mg/m(2) was administered intravenously over 3 h every 3
      weeks. Patients were evaluated for response every 6 weeks. RESULTS: Twenty-five
      patients were enrolled; all were evaluable for toxicity and 23 were evaluable for
      response. There were no complete or partial responses. Thirteen patients (56%)
      had stable disease after two cycles of therapy; five patients (20%) received six
      or more cycles. The median time to progression was 11 weeks; median overall
      survival was 36 weeks. There was considerable grade 3/4 hematological toxicity,
      including neutropenia (48%) and leukopenia (36%). Grade 3/4 non-hematological
      toxicities included grade 3 hypersensitivity reaction (12%) and peripheral
      neuropathy (20%). CONCLUSIONS: Single-agent BMS-247550 (40 mg/m(2)) administered
      every 21 days demonstrated no activity in advanced colorectal cancer. Peripheral
      neuropathy was treatment-limiting.

PMID- 15151951
TI  - Neoadjuvant treatment of unresectable liver disease with irinotecan and 5
      fluorouracil plus folinic acid in colorectal cancer patients.
AB  - BACKGROUND: The aim of this study was to observe the effects of neoadjuvant
      therapy with irinotecan and 5-fluorouracil (5-FU)/folinic acid (FA) on the
      resection rate and survival of colorectal cancer patients with initially
      unresectable hepatic metastases. PATIENTS AND METHODS: Forty patients received
      neoadjuvant chemotherapy comprising irinotecan 180 mg/m(2) administered
      intravenously (i.v.) on day 1, FA 200 mg/m(2) i.v. on days 1 and 2, 5-FU 400
      mg/m(2) i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m(2) as a continuous 48-h
      i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was
      assessed every 12 weeks (six cycles). RESULTS: The objective response rate to
      chemotherapy was 47.5% (n = 19), with two complete responses and disease
      stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients
      undergoing surgery within 2 weeks. Treatment was well tolerated and adverse
      events were typical of the chemotherapy agents used. Twenty-seven (67.5%)
      patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%)
      reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%)
      underwent potentially curative liver resection following chemotherapy.
      Chemotherapy was particularly effective in patients with large metastases on
      entry to the study. The median time to progression is 14.3 months and, at a
      median follow-up of 19 months, all patients are alive. CONCLUSIONS: Neoadjuvant
      therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of
      patients with initially unresectable liver metastases to undergo surgical
      resection. The effects of treatment on survival have yet to be determined.

PMID- 15151953
TI  - A single institutional phase III trial of preoperative chemotherapy with
      hyperfractionation radiotherapy plus surgery versus surgery alone for resectable
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: We conducted a prospective randomized controlled trial comparing
      surgery alone (S) with concurrent chemoradiotherapy followed by surgery (CRT-S)
      for resectable esophageal squamous cell carcinoma (SCC) based on our previous
      report. PATIENTS AND METHODS: One hundred and one patients with stage II/III
      esophageal SCC were randomized to receive either S (50 patients) or CRT-S (51
      patients). The chemoradiotherapy (CRT) consisted of cisplatin 60 mg/m(2)
      intravenously (i.v.) on day 1, 5-fluorouracil (5-FU) 1000 mg/m(2) i.v. on days 2
      5, cisplatin 60 mg/m(2) i.v. on day 22 combined with radiation therapy (45.6 Gy,
      1.2 Gy b.i.d. on days 1-28). Surgery was performed 3-4 weeks after radiotherapy
      was completed. For patients with disease that was stable or responsive to CRT,
      three additional cycles of chemotherapy (cisplatin 60 mg/m(2) i.v. on day 1, 5-FU
      1000 mg/m(2) on days 2-5 every 4 weeks) were given after surgical resection.
      RESULTS: The median age was 62 years. The toxicity of CRT was acceptable and did
      not affect the post-operative morbidity and the duration of hospital stay.
      Clinical response was 86% including 21% of complete response (CR) rate.
      Pathological CR was achieved in 43% [95% confidence interval (CI) 27-59] of the
      patients who underwent surgery after CRT. At a median follow-up of 25 months,
      median overall survival (OS) was 27.3 months in S and 28.2 months in CRT-S (P =
      0.69). Event-free survival (EFS) at 2 years was 51% in S and 49% in CRT-S (P =
      0.93). This trial, which was statistically powered to detect a relatively large
      difference in 2-year survival rate from 30% to 50% with 80% power, was
      discontinued at interim analysis because of the unexpectedly high drop-out rate
      for esophagectomy (31%) and resultant excessive locoregional failure rate in CRT
      S arm (22% versus 12%, P = 0.31), though it was not statistically significant.
      CONCLUSION: Although preoperative CRT induced high clinical and pathological
      response, there was no statistically significant benefit in OS and EFS.

PMID- 15151952
TI  - Trend of incidence, subsite distribution and staging of colorectal neoplasms in
      the 15-year experience of a specialised cancer registry.
AB  - BACKGROUND: Two-thirds of colorectal malignancies are localised in the left colon
      and rectum. Recent studies suggest a trend towards an increase of right-sided
      tumours which might have important implications for screening and surveillance. A
      colorectal cancer registry was set up in Modena, northern Italy, with the purpose
      of examining incidence, subsite distribution and staging of colorectal
      malignancies over a 15-year period. PATIENTS AND METHODS: From 1984 to 1998, 2517
      tumours in 2462 patients were detected and staged with the tumour node metastasis
      (TNM) system. The 'right colon' was considered from caecum to splenic flexure;
      the 'left colon' included descending and sigmoid colon; and the 'rectum' included
      rectosigmoid junction, ampulla and anus. RESULTS: Cancer incidence showed an
      overall increase. Considering the various subsites, an increase of 33.7% in all
      colonic segments was shown whereas rectal tumours tended to decline. TNM staging
      showed a gradual increase of localised lesions (41.2% in 1984 versus 53.3% in
      1998), with a proportional reduction of advanced tumours. CONCLUSIONS: Our study
      indicates an increase of tumour incidence in all colonic segments more than a
      shift to the right colon. TNM staging tended to improve with an appreciable
      increase of localised lesions. These findings could be consequent to a more
      extensive use of colonoscopy.

PMID- 15151954
TI  - A phase II study of single-agent docetaxel in patients with metastatic esophageal
      cancer.
AB  - BACKGROUND: To evaluate the activity and toxicity of docetaxel in patients with
      metastatic esophageal cancer. PATIENTS AND METHODS: Eligible patients had
      histologically confirmed carcinoma of the esophagus with measurable metastatic
      sites according to Response Evaluation Criteria in Solid Tumors (RECIST).
      Patients were either chemotherapy-naive or previously treated with one regimen of
      chemotherapy. Docetaxel 70 mg/m(2) was administered intravenously over 1-2 h,
      every 21 days. RESULTS: Of 52 patients enrolled in this study, three were
      excluded because they did not receive docetaxel due to worsening condition after
      enrollment. Thirty-six patients had received prior platinum-based chemotherapy.
      The majority of patients (94%) had squamous cell carcinoma. Ten of 49 evaluable
      patients [20%; 95% confidence interval (CI) 10-34%] showed a partial response. Of
      the 10 partial responses, six patients had received prior platinum-based
      chemotherapy. Grade 3 or 4 neutropenia was noted in 43 of 49 patients (88%), and
      nine of 49 patients (18%) developed febrile neutropenia. Twenty-eight of 49
      patients (57%) required lenograstim. Grade 3 anorexia and fatigue occurred in
      nine (18%) and six (12%) patients, respectively. Median survival time was 8.1
      months (95% CI 6.6-11.3) and the 1-year survival rate was 35% (95% CI 21-48%).
      CONCLUSIONS: Docetaxel as a single agent is effective in esophageal cancer, but
      careful management of neutropenia is needed.

PMID- 15151955
TI  - A phase II study of carboplatin and paclitaxel in esophageal cancer.
AB  - BACKGROUND: This study was conducted to evaluate the efficacy and toxicity of
      combination carboplatin and paclitaxel in patients with esophageal cancer.
      MATERIALS AND METHODS: Thirty-five patients were enrolled. Patients were treated
      with paclitaxel 200 mg/m(2) intravenously (i.v.) over 3 h and carboplatin i.v. at
      an AUC of 5 mg/h/ml. Thirty-three patients were assessable for toxicity and
      objective response. RESULTS: A total of 166 treatment courses were administered
      with a median of five courses per patient. The objective response rate was 43%
      [90% confidence interval (CI) 0.3-0.58] by the intention-to-treat analysis. The
      median response duration was 2.8 months (90% CI 2.1-5.4). The median survival
      time was 9 months (90% CI 7-13.8) and the 1-year survival rate was 43% (90% CI
      0.29-0.57). The major grade 3-4 toxicity observed was neutropenia, occurring in
      17 patients (52%). There were no treatment-related deaths. CONCLUSIONS: The
      combination of carboplatin and paclitaxel is an moderately active and tolerable
      regimen in advanced esophageal cancer.

PMID- 15151956
TI  - Consensus report on the use of somatostatin analogs for the management of
      neuroendocrine tumors of the gastroenteropancreatic system.
AB  - This consensus report gives a detailed description of the use of somatostatin
      analogs in the management of neuroendocrine tumors of the gastroenteropancreatic
      system. As background information we have outlined critical aspects of the
      pathology, the use of tumor markers, a definition of functional and non
      functional digestive neuroendocrine tumors, different imaging modalities,
      surgical considerations, liver embolization and the use of cytotoxic drugs as
      well as interferon. Included in the report is an overview of somatostatin,
      somatostatin analogs and its receptor expression in different neuroendocrine
      tumors. It will also define the binding affinities of different somatostatin
      analogs to the five different subtypes of somatostatin receptor. We compare the
      efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side
      effects are described and we provide practical information on somatostatin analog
      treatment.

PMID- 15151958
TI  - The longitudinal relationship of hemoglobin, fatigue and quality of life in
      anemic cancer patients: results from five randomized clinical trials.
AB  - BACKGROUND: Anemia is common in cancer and has been associated with fatigue and
      reduced health-related quality of life (HRQOL). We report the association between
      hemoglobin and fatigue and the impact of reducing fatigue on several domains of
      HRQOL. PATIENTS AND METHODS: These analyses were based on five randomized trials.
      Patients completed the Functional Assessment of Cancer Therapy (FACT) Anemia
      scales and numeric rating scales of Energy, Activity and Overall Health at
      baseline and after the 12-week treatment period. t-tests and linear regression
      models were used to evaluate associations. Analyses were stratified into three
      groups: solid tumor chemotherapy patients, lymphoproliferative malignancy
      chemotherapy patients and non-chemotherapy patients. RESULTS: Adjusted mean
      differences (95% CI) in FACT Fatigue change scores between hemoglobin responders
      (> or =2 g/dl increase) and non-responders were 3.0 (1.2, 4.7), 2.8 (0.6, 5.0)
      and 5.8 (2.2, 9.5) among the solid tumor, lymphoproliferative malignancy and non
      chemotherapy groups, respectively. Significantly greater improvements (P <0.01)
      were observed in the FACT well-being scales for patients with meaningful
      improvement in fatigue (FACT Fatigue change score > or =3 points). After
      controlling for other factors, patients whose fatigue improved reported
      substantially greater improvements in energy, ability to perform usual activities
      and overall health (P <0.0001). CONCLUSIONS: Across five trials of cancer
      patients on and off chemotherapy, hemoglobin response was associated with
      meaningful improvements in fatigue, which, in turn, was associated with improved
      physical, functional, emotional and overall well-being.

PMID- 15151957
TI  - Finasteride and bicalutamide as primary hormonal therapy in patients with
      advanced adenocarcinoma of the prostate.
AB  - BACKGROUND: Medical or surgical castration is effective in advanced prostate
      cancer but with profound side-effects, particularly on sexual function.
      Effective, less toxic therapies are needed. This study examined whether the
      addition of finasteride to high-dose bicalutamide enhanced disease control, as
      measured by additional decreases in serum prostate-specific antigen (PSA).
      PATIENTS AND METHODS: Forty-one patients with advanced prostate cancer received
      bicalutamide (150 mg/day). Finasteride (5 mg/day) was added at first PSA nadir.
      Serum PSA was measured every 2 weeks until disease progression. Questionnaires
      were administered to assess sexual function. RESULTS: Median follow-up is 3.9
      years. At the first PSA nadir, median decrease in PSA from baseline was 96.5%.
      Thirty of 41 patients (73%) achieved a second PSA nadir and median decrease of
      98.5% from baseline. Median time to each nadir was 3.7 and 5.8 weeks,
      respectively. Median time to treatment failure was 21.3 months. Toxicities were
      minor, including gynecomastia. Seventeen of 29 (59%) and 12 of 24 (50%) men had
      normal sex drive at baseline and at second PSA nadir, respectively. One-third of
      men had spontaneous erection at both time points. CONCLUSION: Finasteride
      provides additional intracellular androgen blockade when added to bicalutamide.
      Duration of control is comparable to castration, with preserved sexual function
      in some patients.

PMID- 15151959
TI  - Central nervous system side-effects of 5-HT3-receptor antagonists in elderly
      cancer patients treated with chemotherapy.

PMID- 15151960
TI  - Intratumoral injection of herpes simplex virus HF10 in recurrent breast cancer.

PMID- 15151961
TI  - Serum and plasma vascular endothelial growth factor levels in testicular cancer
      patients.

PMID- 15151962
TI  - Late local recurrences in a randomized trial comparing conservative treatment
      with total mastectomy in early breast cancer patients: the impact of receptor
      status on local relapse.

PMID- 15151964
TI  - What do patients receiving palliative care for cancer and their families want to
      be told? A Canadian and Australian qualitative study.
AB  - OBJECTIVE: To obtain feedback from patients receiving palliative care and their
      relatives from various ethnic backgrounds about their experiences of the
      disclosure process and their satisfaction with information sharing during the
      illness. DESIGN: A qualitative study with semistructured single interviews.
      SETTING: Perth, Western Australia, and Winnipeg, Manitoba, Canada. PARTICIPANTS:
      72 participants registered with palliative care: 21 patient-family dyads in Perth
      and 14 dyads and 2 patients in Winnipeg. RESULTS: Participants described their
      experiences in great detail. The analysis indicates that in information sharing
      the process is as important as the content. The timing, management, and delivery
      of information and perceived attitude of practitioners were critical to the
      process. This applied to information interactions at all stages of the illness.
      Main content areas mentioned related to prognosis and hope. Hope can be conveyed
      in different ways. Secondary information from various sources is accessed and
      synthesised with the primary information. All patients, regardless of origin,
      wanted information about their illness and wanted it fully shared with relatives.
      Almost all patients requested prognostic information, and all family members
      respected their wishes. Information was perceived as important for patient-family
      communication. Information needs of patient and family changed and diverged as
      illness progressed, and communication between them became less verbally explicit.
      CONCLUSIONS: Information delivery for patients needs to be individualised with
      particular attention to process at all stages of illness. Patients and families
      use secondary sources of information to complement and verify information given
      by health carers.

PMID- 15151966
TI  - Assessment of monitor conditions for the display of radiological diagnostic
      images and ambient lighting.
AB  - Diagnostic efficacy is related to viewing conditions. An increasing number of
      radiology departments are using workstations for reporting and it was the aim of
      this study to assess monitor performance and ambient lighting in areas allocated
      to soft-copy reporting and review. The study was performed in 4 Dublin hospitals
      and 20 monitors were examined. Using a Society of Motion Pictures and Television
      Engineers' (SMPTE) test pattern, maximum luminance, spatial uniformity of
      luminance, temporal luminance stability, brightness and contrast resolution
      (gamma), geometry and ambient lighting was assessed. The results demonstrated
      that although temporal luminance stability and spatial uniformity appeared to be
      at acceptable levels, maximum luminance and gamma value variations were noted,
      with maximum luminance and geometry values often not complying with published
      guidelines. Cleaning the monitor face had no impact. 90% of viewing areas had
      acceptable ambient lighting levels. The data presented demonstrate that monitors
      examined were not operating at optimal levels for all performance parameters and
      inclusion of regular assessments of monitors should be part of an imaging
      department's ongoing quality assurance programme.

PMID- 15151965
TI  - Authors' perceptions of electronic publishing: two cross sectional surveys.
AB  - OBJECTIVES: To evaluate how acceptable authors find the BMJ's current practice of
      publishing short versions of research articles in the paper journal and a longer
      version on the web and to determine authors' attitudes towards publishing only
      abstracts in the paper journal and publishing unedited versions on bmj.com once
      papers have been accepted for publication. DESIGN: Two cross sectional surveys.
      SETTING: General medical journal. PARTICIPANTS: Survey 1: corresponding authors
      of a consecutive sample of published BMJ research articles that had undergone the
      ELPS (electronic long, paper short) process. Survey 2: corresponding authors of
      consecutive research articles submitted to BMJ. RESULTS: Response rates were 90%
      (104/115) in survey 1 and 75% (213/283) in survey 2. ELPS is largely acceptable
      to BMJ authors, but there is some concern that electronic information is not
      permanent and uncertainty about how versions are referenced. While authors who
      had experienced ELPS reported some problems with editors shortening papers, most
      were able to rectify these. Overall, 70% thought that the BMJ should continue to
      use ELPS; 49% thought that publishing just the abstract in the printed journal
      with the full version only on bmj.com was unacceptable; and 23% thought it
      unacceptable to post unedited versions on bmj.com once a paper had been accepted
      for publication. CONCLUSIONS: It is acceptable to authors to publish short
      versions of research articles in the printed version of a general medical journal
      with longer versions on the website. Authors dislike the idea of publishing only
      abstracts in the printed journal but are in favour of posting accepted articles
      on the website ahead of the printed version.

PMID- 15151967
TI  - Effect of multislice scanners on patient dose from routine CT examinations in
      East Anglia.
AB  - As part of the dose optimization process, the Ionising Radiation (Medical
      Exposure) Regulations 2000 include requirements relating to the assessment of
      patient dose, and the setting and subsequent review of diagnostic reference
      levels. In East Anglia, audits of effective dose in CT have been carried out in
      1996, 1999 and 2002. In the 2002 audit, nine of the 14 scanners assessed had been
      replaced since the previous audit. Eight of the new scanners were multislice
      scanners, acquiring up to 16 slices in a single rotation. The objective of the
      2002 audit was to investigate the effect of the introduction of these multislice
      scanners on patient doses from routine CT examinations. Exposure parameters were
      collected for 10 different types of routine CT examination. In excess of 550 sets
      of patient data were obtained. For each of these, effective doses were calculated
      using the results of Monte Carlo simulations published by the National
      Radiological Protection Board. Averaged across all 10 examinations, regional mean
      effective doses are 34% higher than in 1999. The multislice scanners in the
      region give, on average, 35% more effective dose than the single-slice scanners.
      The effect of collimation in multislice scanners makes these effective dose
      differences most notable for examinations that use narrow slice widths. Further
      optimization of exposures on multislice scanners has the potential to reduce the
      differences observed between single-slice and multislice doses. However, when
      taken in combination with the increased use of CT in many hospitals, the
      effective dose increases observed are likely to result in a significant increase
      in the already substantial collective radiation dose from CT.

PMID- 15151968
TI  - Optimization of radiographic parameters for paediatric cardiac angiography.
AB  - In the paediatric cardiac catheterization laboratory the reduction of the
      radiation dose of diagnostic and interventional procedures is of high priority.
      Therefore, we performed an experimental study for optimizing the automatic
      exposure control (AEC) for cardiac angiography. With a Philips Integris BH 5000
      system, six AEC programs were configured to acquire X-ray images of 8 cm to 18.5
      cm thick PMMA phantoms at tube voltages between 50 kV and 90 kV, with 0.2 mm or
      0.4 mm Cu filters and with or without an anti-scatter grid. At constant detector
      dose, entrance dose (ED) and image quality were evaluated as functions of the
      voltage. Changes in image quality were determined by the differential signal-to
      noise ratio measured within regions of low (SNRb) and high (SNRd) attenuation. At
      equal voltages, ED saving was approximately 29% with the 0.4 mm Cu beam filtering
      as compared with 0.2 mm Cu, largely independent of object thickness. SNRb and
      SNRd were only dependent on the voltage. While SNRb was high at low voltages,
      SNRd showed a maximum at approximately 79 kV. Using a grid, ED increased with
      increasing object thickness by a factor of 1.9 to 3.5. At equal voltages, the
      grid led to significant image improvements, with SNRb and SNRd increasing by 27%
      and 11%, respectively. SNRb and SNRd are useful descriptors of the image quality
      in cardiac angiography. Highest image quality was found with tube voltages
      between 55 kV and 77 kV, independently of object thickness. To minimize dose, the
      thickness of the copper filter should be chosen to be as large as possible
      provided the tube's power limit allows keeping the voltage below the upper limit.
      In view of the substantial image improvement, the use of a grid is recommended
      for all patients, even for newborns.

PMID- 15151969
TI  - Experimental evidence to support the hypothesis that damage to vascular
      endothelium plays the primary role in the development of late radiation-induced
      CNS injury.
AB  - Experimental evidence has been obtained to support the view that late necrosis in
      the brain, after irradiation, is a consequence of damage to the vascular system.
      Rats were locally irradiated to the brain with a single dose of 25 Gy of X-rays
      and their response was compared with rats given the same treatment after
      administration of the radioprotector, Gammaphos. Time-dependent changes in
      endothelial cell number were determined for up to 65 weeks after irradiation. The
      complex pattern of changes in endothelial cell number, seen after irradiation
      alone, was not found in animals receiving Gammaphos prior to irradiation. The
      initial marked loss of endothelial cells, seen after 24 h in unprotected animals,
      was effectively prevented by the pre-administration of Gammaphos. The subsequent
      slow decline in endothelial cell density in Gammaphos treated animals was
      insufficient to induce an abortive attempt at endothelial cell re-population.
      This occurred between 26 and 52 weeks after irradiation in unprotected animals.
      By 65 weeks after irradiation <10% of animals receiving Gammaphos showed necrosis
      on histological evaluation. This compared with approximately 50% of the animals
      showing necrosis that had not received the radioprotector. Since the
      radioprotector is restricted to the vasculature of the brain these data indicate
      that endothelium is the primary target cell population, damage to which leads to
      the development of late radiation-induced necrosis in the brain.

PMID- 15151970
TI  - Clinical implementation of dynamic intensity-modulated radiotherapy:
      radiographers' perspectives.
AB  - The ability of intensity-modulated radiotherapy (IMRT) to sculpt the dose
      distribution closely around the tumour volume has the potential to have a major
      impact on radiotherapy clinical practice. However, dynamic IMRT treatment
      delivery differs from that of conventional treatment because of the constantly
      moving multileaf collimators (MLCs) and higher monitor units (MUs) required. The
      implementation of new technology can be affected by the users response.
      Radiographers' attitudes regarding technology and their perceptions of the
      clinical implementation of IMRT were explored using a qualitative study based on
      semi-structured interviews. 16 radiographers were interviewed and data was
      analysed using a framework analysis to identify themes and categories. The
      majority of radiographers (12/16) demonstrated positive attitudes regarding
      technology. The introduction of IMRT was seen to be stimulating and motivating.
      Negative aspects were associated with increased stress from learning new skills
      and the additional pressure of the increased workload. Although there were
      contradictory views regarding the effect of the increased use of technology on
      the patient-radiographer relationship, technological skills and patient care were
      not found to be mutually exclusive. Radiographers' perceptions regarding the
      clinical implementation of IMRT appeared to be influenced by their mainly
      positive attitudes regarding technology. With the current problems of recruitment
      and retention of radiographers, full exploitation of modern technology could be
      used to improve job satisfaction. However, careful integration is required to
      balance training needs with service demands.

PMID- 15151972
TI  - Short communication: fused deposition models from CT scans.
AB  - Fused deposition modelling (FDM) is a new method for rapid prototyping, a
      technique that produces models of objects from computer files. The most commonly
      used rapid prototyping technique for medical applications is stereolithography,
      but FDM has several potential advantages. This paper is concerned with the
      accuracy of an FDM model of a sheep lumbar vertebra using data from a CT scan.
      The model and the original vertebra were compared by making measurements with
      vernier callipers and by laser scanning. Visually, the model reproduced the
      features of the original object; this conclusion was supported by a comparison of
      the laser scans. Discrepancies in measurements were comparable with those of
      models produced using other rapid prototyping techniques, demonstrating that FDM
      is a viable method for making models for clinical use.

PMID- 15151971
TI  - General interest: the British Journal of Radiology and the Second World War: a
      radiologist's retrospective.

PMID- 15151973
TI  - Case report: MRI evaluation of congenital coronary artery fistulae.
AB  - Congenital coronary artery fistula is a rare disease and MRI is a promising
      technique that may be useful to demonstrate the coronary artery tree. We report
      three patients who underwent cardiac MRI to investigate right coronary artery
      fistulae. On clinical examination, a continuous murmur was heard along the left
      sternal border, and chest X-ray showed moderate cardiomegaly with enlargement of
      right chambers in all patients. Transthoracic Doppler echocardiography showed
      fistulae in two cases; the third case was not demonstrated by transthoracic or
      transoesophageal echocardiography. MRI demonstrated the course of the fistulous
      vessels in all patients. All patients underwent surgical closure of their
      coronary artery fistulae. MRI may show detailed anatomy of congenital coronary
      artery fistulae and may be useful as an additional non-invasive method in their
      investigation.

PMID- 15151974
TI  - Case report: appearance of uterine cervical lymphoma on MRI: a case report and
      review of the literature.
AB  - We present the appearances on CT and MRI of a case of non-Hodgkin's lymphoma
      (NHL) of uterine cervix. A 41-year-old woman presented with a short history of
      urinary symptoms and menorrhagia. Previous cervical smears were normal.
      Clinically, the cervix was replaced by a huge ulcerating mass. Biopsy showed
      malignant high grade B-cell NHL. T(2) weighted MRI of the pelvis showed a 12 cm
      intermediate signal mass replacing the cervix, with infiltration of the vagina
      and left parametrium, and bilateral internal iliac lymphadenopathy. Whole body CT
      imaging showed lymphoma in the kidneys and pancreas, the latter associated with
      biliary obstruction. The patient is in complete remission 7 months post
      chemotherapy, radiotherapy and stenting of biliary stricture. The success of the
      cervical cancer screening programme has lead to a reduction in the number of
      cases of advanced cervical carcinoma and the presence of an unusually large
      homogeneous cervical tumour, with relatively scant necrosis should prompt
      suspicion of a less common histology such as NHL.

PMID- 15151975
TI  - Case report: adenosquamous carcinoma of the liver successfully treated with
      repeated transcatheter arterial infusion chemotherapy (TACE) with degradable
      starch microspheres.
AB  - This report describes a 58-year-old female with adenosquamous carcinoma (ASC) of
      the liver presenting with right lower abdominal pain. In most ASC of the liver,
      surgery is the first choice of treatment. However, surgery often seems to be
      ineffective because of the aggressive behaviour of this disease. At surgical
      laparotomy in the present case, there was a large tumour occupying the entire
      right lobe of the liver and invading the diaphragm. Thus, partial hepatectomy was
      performed. For the residual tumour, we performed repeated transcatheter arterial
      infusion chemotherapy with degradable starch microspheres (DSM). After four
      sessions of transcatheter arterial infusion chemotherapy, tumour size decreased
      remarkably and tumour markers had also decreased. Despite the poor prognosis, the
      patient remains alive and well 12 months after laparotomy. It is suggested that
      minimally invasive transcatheter infusion chemotherapy with DSM can be an
      effective treatment preserving a high quality of life.

PMID- 15151977
TI  - Case report: MRI in the diagnosis of testicular Leydig cell tumour.
AB  - We report the appearance of three cases of Leydig cell tumours on MRI. This
      imaging method showed well-defined and peripheral intratesticular tumours
      displaying marked and homogeneous enhancement when contrast medium was used. This
      latter finding was only observed in Leydig cell tumours when they were compared
      in a series of 104 patients with different scrotal pathologies.

PMID- 15151976
TI  - Case report: radical radiotherapy for early laryngeal cancer in a patient with
      human immunodeficiency virus: no evidence of increased toxicity.
AB  - There are very few reported cases of laryngeal squamous cell carcinoma (SCC) in
      patients with a background of human immunodeficiency virus (HIV) infection. We
      report a case of a 42-year-old man who developed a T2 N0 left vocal cord well
      differentiated SCC with an 11 year history of HIV infection. He successfully
      completed a course of radical radiotherapy 66 Gy in 33 fractions over 47 days.
      During his treatment he experienced only a grade 1 Radiation Therapy Oncology
      Group (RTOG) acute toxicity reaction to the larynx and no weight loss. At 32
      months follow up he remains disease free and has no significant late morbidity.
      Prior to his radiotherapy his CD4 count was 350 cells mm(-3); we discuss the view
      that the treatment chosen needs to be individually tailored with respect to the
      patient's immune status.

PMID- 15151978
TI  - Case report: drug interference with MIBG uptake in a patient with metastatic
      paraganglioma.
AB  - Metaiodobenzylguanidine (MIBG) labelled with iodine-131 ((131)I) has become a
      well established therapeutic tool for inoperable metastastic tumours of
      paraganglioma. There are different pharmacological substances known to interfere
      with MIBG-uptake which may result in a false negative MIBG scan. We present the
      case of a 26-year-old male polytoxicomanic patient with metastatic paraganglioma,
      who underwent MIBG therapy. During earlier therapies, MIBG uptake in the
      metastatic lesions was very high. A post-therapeutic whole-body scan subsequent
      to recent (131)I-MIBG therapy failed to detect the vast majority of metastatic
      lesions-except for two. (18)F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET) showed metastases with a similar distribution to the initial
      MIBG scan. The possible reasons for the discrepancy in the findings of the MIBG
      scans and the (18)F-FDG-PET scan are discussed with special emphasis on drug
      intake prior to MIBG administration, increased MIBG turn-over and unknown drug
      mixture interference with MIBG uptake.

PMID- 15151979
TI  - Case report: delayed post-contrast fluid-attenuated inversion recovery image for
      depicting meningeal carcinomatosis.
AB  - We present a case of intracranial meningeal carcinomatosis that was visualized
      more clearly on a delayed contrast-enhanced fluid-attenuated inversion recovery
      (FLAIR) MRI than on other regular post-contrast MRI.

PMID- 15151980
TI  - Pictorial review: MRI features of foot and ankle injuries in ballet dancers.
AB  - Foot and ankle pain is common in ballet dancers. Although clinical examination
      often points to the underlying cause, imaging is often necessary to confirm the
      diagnosis and thus ensure appropriate future management. Factors predisposing to
      the increased incidence of injuries in this population include the classical
      position in which ballet dancers stand, which is on the tips of the toes in the
      en pointe position or on the balls of the feet in the demi-pointe position.
      Furthermore, the repetitious nature of ballet and the long hours spent rehearsing
      cause over-use injuries. The causes of foot and ankle pain can be thought of in
      four different groups: the impingement syndromes; tendon abnormalities; osseous
      pathology; and ligament abnormalities. These will be discussed and illustrated.

PMID- 15151981
TI  - Case of the month: an unusual cause of neck pain.

PMID- 15151982
TI  - PAR-3 is required for epithelial cell polarity in the distal spermatheca of C.
      elegans.
AB  - PAR-3 is localized asymmetrically in epithelial cells in a variety of animals
      from Caenorhabditis elegans to mammals. Although C. elegans PAR-3 is known to act
      in early blastomeres to polarize the embryo, a role for PAR-3 in epithelial cells
      of C. elegans has not been established. Using RNA interference to deplete PAR-3
      in developing larvae, we discovered a requirement for PAR-3 in spermathecal
      development. Spermathecal precursor cells are born during larval development and
      differentiate into an epithelium that forms a tube for the storage of sperm. Eggs
      must enter the spermatheca to complete ovulation. PAR-3-depleted worms exhibit
      defects in ovulation. Consistent with this phenotype, PAR-3 is transiently
      expressed and localized asymmetrically in the developing somatic gonad, including
      the spermathecal precursor cells of L4 larvae. We found that the defect in
      ovulation can be partially suppressed by a mutation in IPP-5, an inositol
      polyphosphate 5-phosphatase, indicating that one effect of PAR-3 depletion is
      disruption of signaling between oocyte and spermatheca. Microscopy revealed that
      the distribution of AJM-1, an apical junction marker, and apical microfilaments
      are severely affected in the distal spermatheca of PAR-3-depleted worms. We
      propose that PAR-3 activity is required for the proper polarization of
      spermathecal cells and that defective ovulation results from defective distal
      spermathecal development.

PMID- 15151983
TI  - Differential stability of beta-catenin along the animal-vegetal axis of the sea
      urchin embryo mediated by dishevelled.
AB  - beta-Catenin has a central role in the early axial patterning of metazoan
      embryos. In the sea urchin, beta-catenin accumulates in the nuclei of vegetal
      blastomeres and controls endomesoderm specification. Here, we use in-vivo
      measurements of the half-life of fluorescently tagged beta-catenin in specific
      blastomeres to demonstrate a gradient in beta-catenin stability along the animal
      vegetal axis during early cleavage. This gradient is dependent on GSK3beta
      mediated phosphorylation of beta-catenin. Calculations show that the difference
      in beta-catenin half-life at the animal and vegetal poles of the early embryo is
      sufficient to produce a difference of more than 100-fold in levels of the protein
      in less than 2 hours. We show that dishevelled (Dsh), a key signaling protein, is
      required for the stabilization of beta-catenin in vegetal cells and provide
      evidence that Dsh undergoes a local activation in the vegetal region of the
      embryo. Finally, we report that GFP-tagged Dsh is targeted specifically to the
      vegetal cortex of the fertilized egg. During cleavage, Dsh-GFP is partitioned
      predominantly into vegetal blastomeres. An extensive mutational analysis of Dsh
      identifies several regions of the protein that are required for vegetal cortical
      targeting, including a phospholipid-binding motif near the N-terminus.

PMID- 15151984
TI  - Roles of the C. elegans cyclophilin-like protein MOG-6 in MEP-1 binding and
      germline fates.
AB  - The switch from spermatogenesis to oogenesis in the Caenorhabditis elegans
      hermaphrodite requires mog-6, which post-transcriptionally represses the fem-3
      RNA. In this study, we show that mog-6 codes for a divergent nuclear cyclophilin,
      in that a conserved domain is not required for its function in the sperm-oocyte
      switch. MOG-6 binds to the nuclear zinc finger protein MEP-1 through two separate
      domains that are essential for the role of MOG-6 in the sperm-oocyte switch. We
      propose that MOG-6 has a function distinct from that of prevailing cyclophilins
      and that its binding to MEP-1 is essential for germline sex determination.
      Finally, we found that gld-3 mog-6 mutants develop germline tumors, suggesting
      that mog-6 might function in the decision between mitosis and meiosis.

PMID- 15151985
TI  - Fgf signalling controls the dorsoventral patterning of the zebrafish embryo.
AB  - The establishment of dorsoventral (DV) patterning in vertebrate embryos depends
      on the morphogenic activity of a group of Tgfbeta superfamily members, the bone
      morphogenetic proteins (Bmps) (which specify ventral cell fates), and on their
      interaction with their dorsally secreted cognate inhibitors chordin and noggin.
      In the zebrafish, genetic analysis has revealed that Bmp2b and Bmp7, as well as
      their antagonist chordin, are required for proper DV patterning. The expression
      of Bmp genes is initially activated in the whole blastula. Well before the
      beginning of gastrulation, Bmp gene expression progressively disappears from the
      dorsal side to become restricted to the ventral part of the embryo. We show that
      this early restriction of Bmp gene expression, which occurs independently of
      noggin and chordin, is an essential step in the establishment of DV patterning.
      The progressive ventral restriction of Bmp gene transcripts is coincident with
      the spreading of Fgf activity from the dorsal side of the embryo, suggesting that
      Fgf signalling is implicated in dorsal downregulation of Bmp gene expression. In
      accordance with this, activation of the Fgf/Ras/Mapk-signalling pathway inhibits
      ventral Bmp gene expression, thereby causing a dorsalisation of the embryo.
      Conversely, inhibition of Fgf signalling causes Bmp gene expression to expand
      dorsally, leading to an expansion of ventral cell fates. In accordance with an
      important role of Fgf signalling in the DV patterning of the zebrafish, we show
      that loss of Fgf8 function enhances the ventralisation of chordin-deficient
      embryos. Our results thereby demonstrate that pre-gastrula stage Fgf-signalling
      is essential to delimit the expression domain of the genes encoding the
      functional morphogen of the dorsoventral axis of the early zebrafish embryo.

PMID- 15151986
TI  - alphavbeta3 integrin-dependent endothelial cell dynamics in vivo.
AB  - A major challenge confronting developmental cell biologists is to understand how
      individual cell behaviors lead to global tissue organization. Taking advantage of
      an endothelial cell-specific marker and scanning time-lapse microscopy, we have
      examined the formation of the primary vascular pattern during avian
      vasculogenesis. Five types of distinguishable endothelial cell motion are
      observed during formation of a vascular plexus: (1) global tissue deformations
      that passively convect endothelial cells; (2) vascular drift, a sheet-like medial
      translocation of the entire vascular plexus; (3) structural rearrangements, such
      as vascular fusion; (4) individual cell migration along existing endothelial
      structures; and (5) cell process extension into avascular areas, resulting in new
      links within the plexus. The last four types of motion are quantified and found
      to be reduced in the presence of an alphavbeta3 integrin inhibitor. These dynamic
      cell motility data result in new hypotheses regarding primordial endothelial cell
      behavior during embryonic vasculogenesis.

PMID- 15151987
TI  - Distinct roles of Rac1/Cdc42 and Rho/Rock for axon outgrowth and nucleokinesis of
      precerebellar neurons toward netrin 1.
AB  - During embryonic development, tangentially migrating precerebellar neurons emit a
      leading process and then translocate their nuclei inside it (nucleokinesis).
      Netrin 1 (also known as netrin-1) acts as a chemoattractant factor for
      neurophilic migration of precerebellar neurons (PCN) both in vivo and in vitro.
      In the present work, we analyzed Rho GTPases that could direct axon outgrowth
      and/or nuclear migration. We show that the expression pattern of Rho GTPases in
      developing PCN is consistent with their involvement in the migration of PCN from
      the rhombic lips. We report that pharmacological inhibition of Rho enhances axon
      outgrowth of PCN and prevents nuclei migration toward a netrin 1 source, whereas
      inhibition of Rac and Cdc42 sub-families impair neurite outgrowth of PCN without
      affecting migration. We show, through pharmacological inhibition, that Rho
      signaling directs neurophilic migration through Rock activation. Altogether, our
      results indicate that Rho/Rock acts on signaling pathways favoring nuclear
      translocation during tangential migration of PCN. Thus, axon extension and
      nuclear migration of PCN in response to netrin 1 are not strictly dependent
      processes because: (1) distinct small GTPases are involved; (2) axon extension
      can occur when migration is blocked; and (3) migration can occur when axon
      outgrowth is impaired.

PMID- 15151988
TI  - Restriction of sonic hedgehog signalling during early tooth development.
AB  - The signalling peptide encoded by the sonic hedgehog gene is restricted to
      localised thickenings of oral epithelium, which mark the first morphological
      evidence of tooth development, and is known to play a crucial role during the
      initiation of odontogenesis. We show that at these stages in the murine
      mandibular arch in the absence of epithelium, the Shh targets Ptc1 and Gli1 are
      upregulated in diastema mesenchyme, an edentulous region between the sites of
      molar and incisor tooth formation. This ectopic expression is not associated with
      Shh transcription but with Shh protein, undetectable in the presence of
      epithelium. These findings suggest that, in diastema mesenchyme, restriction of
      Shh activity is dependent upon the overlying epithelium. This inhibitory activity
      was demonstrated by the ability of transplanted diastema epithelium to
      downregulate Ptc1 in tooth explants, and for isolated diastema mesenchyme to
      express Ptc1. A candidate inhibitor in diastema mesenchyme is the
      glycosylphosphatidylinositol-linked membrane glycoprotein Gas1. Gas1 is normally
      expressed throughout mandibular arch mesenchyme; however, in the absence of
      epithelium this expression was downregulated specifically in the diastema where
      ectopic Shh protein was identified. Although Shh signalling has no effect upon
      Gas1 expression in mandibular arch mesenchyme, overexpression of Gas1 results in
      downregulation of ectopic Ptc1. Therefore, control of the position of tooth
      initiation in the mandibular arch involves a combination of Shh signalling at
      sites where teeth are required and antagonism in regions destined to remain
      edentulous.

PMID- 15151989
TI  - Identification of new members of Fertilisation Independent Seed Polycomb Group
      pathway involved in the control of seed development in Arabidopsis thaliana.
AB  - In higher plants, double fertilisation initiates seed development. One sperm cell
      fuses with the egg cell and gives rise to the embryo, the second sperm cell fuses
      with the central cell and gives rise to the endosperm. The endosperm develops as
      a syncytium with the gradual organisation of domains along an anteroposterior
      axis defined by the position of the embryo at the anterior pole and by the
      attachment to the placenta at the posterior pole. We report that ontogenesis of
      the posterior pole in Arabidopsis thaliana involves oriented migration of nuclei
      in the syncytium. We show that this migration is impaired in mutants of the three
      founding members of the FERTILIZATION INDEPENDENT SEED (FIS) class, MEDEA (MEA),
      FIS2 and FERTILIZATION INDEPENDENT ENDOSPERM (FIE). A screen based on a green
      fluorescent protein (GFP) reporter line allowed us to identify two new loci in
      the FIS pathway, medicis and borgia. We have cloned the MEDICIS gene and show
      that it encodes the Arabidopsis homologue of the yeast WD40 domain protein
      MULTICOPY SUPRESSOR OF IRA (MSI1). The mutations at the new fis loci cause the
      same cellular defects in endosperm development as other fis mutations, including
      parthenogenetic development, absence of cellularisation, ectopic development of
      posterior structures and overexpression of the GFP marker.

PMID- 15151990
TI  - nemo-like kinase is an essential co-activator of Wnt signaling during early
      zebrafish development.
AB  - Wnt/beta-catenin signaling regulates many aspects of early vertebrate
      development, including patterning of the mesoderm and neurectoderm during
      gastrulation. In zebrafish, Wnt signaling overcomes basal repression in the
      prospective caudal neurectoderm by Tcf homologs that act as inhibitors of Wnt
      target genes. The vertebrate homolog of Drosophila nemo, nemo-like kinase (Nlk),
      can phosphorylate Tcf/Lef proteins and inhibit the DNA-binding ability of beta
      catenin/Tcf complexes, thereby blocking activation of Wnt targets. By contrast,
      mutations in a C. elegans homolog show that Nlk is required to activate Wnt
      targets that are constitutively repressed by Tcf. We show that overexpressed
      zebrafish nlk, in concert with wnt8, can downregulate two tcf3 homologs, tcf3a
      and tcf3b, that repress Wnt targets during neurectodermal patterning. Inhibition
      of nlk using morpholino oligos reveals essential roles in regulating
      ventrolateral mesoderm formation in conjunction with wnt8, and in patterning of
      the midbrain, possibly functioning with wnt8b. In both instances, nlk appears to
      function as a positive regulator of Wnt signaling. Additionally, nlk strongly
      enhances convergent/extension phenotypes associated with wnt11/silberblick,
      suggesting a role in modulating cell movements as well as cell fate.

PMID- 15151991
TI  - Binding of SeqA protein to hemi-methylated GATC sequences enhances their
      interaction and aggregation properties.
AB  - The SeqA protein regulates chromosome initiation and is involved in segregation
      in Escherichia coli. One SeqA protein binds to two hemi-methylated GATC sequences
      to form a stable SeqA-DNA complex. We found that binding induced DNA bending,
      which was pronounced when the two sequences were on the same face of the DNA. Two
      SeqA molecules bound cooperatively to each pair of hemi-methylated sites when the
      spacing between the sites was < or = 30 bp. This cooperative binding was able to
      stabilize the binding of a wild type to a single hemi-methylated site, or mutant
      form of SeqA protein to hemi-methylated sites, although such binding did not
      occur without cooperative interaction. Two cooperatively bound SeqA molecules
      interacted with another SeqA bound up to 185 bp away from the two bound SeqA
      proteins, and this was followed by aggregation of free SeqA proteins onto the
      bound proteins. These results suggest that the stepwise interaction of SeqA
      proteins with hemi-methylated GATC sites enhances their interaction and leads to
      the formation of SeqA aggregates. Cooperative interaction followed by aggregation
      may be the driving force for formation of the SeqA foci that appear to be located
      behind replication forks.

PMID- 15151992
TI  - Interaction of nick-directed DNA mismatch repair and loop repair in human cells.
AB  - In human cells, large DNA loop heterologies are repaired through a nick-directed
      pathway independent of mismatch repair. However, a 3'-nick generated by
      bacteriophage fd gene II protein heterology is not capable of stimulating loop
      repair. To evaluate the possibility that a mismatch near a loop could induce both
      repair types in human cell extracts, we constructed and tested a set of DNA
      heteroduplexes, each of which contains a combination of mismatches and loops. We
      have demonstrated that a strand break generated by restriction endonucleases 3'
      to a large loop is capable of provoking and directing loop repair. The repair of
      3'-heteroduplexes in human cell extracts is very similar to that of 5'
      heteroduplex repair, being strand-specific and highly biased to the nicked
      strand. This observation suggests that the loop repair pathway possesses
      bidirectional repair capability similar to that of the bacterial loop repair
      system. We also found that a nick 5' to a coincident mismatch and loop can
      apparently stimulate the repair of both. In contrast, 3'-nick-directed repair of
      a G-G mismatch was reduced when in the vicinity of a loop (33 or 46 bp between
      two sites). Increasing the distance separating the G-G mismatch and loop by 325
      bp restored the efficiency of repair to the level of a single base-base mismatch.
      This observation suggests interference between 3'-nick-directed large loop repair
      and conventional mismatch repair systems when a mispair is near a loop. We
      propose a model in which DNA repair systems avoid simultaneous repair at adjacent
      sites to avoid the creation of double-stranded DNA breaks.

PMID- 15151993
TI  - Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of
      mitochondrial metabolism in rat islets.
AB  - Mutations in the transcription factor IPF1/PDX1 have been associated with type 2
      diabetes. To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction
      of rat islets with an adenoviral construct encoding a dominant negative form of
      PDX1. After 2 days, there was a marked inhibition of insulin secretion in
      response to glucose, leucine, and arginine. Increasing cAMP levels with forskolin
      and isobutylmethylxanthine restored glucose-stimulated insulin secretion,
      indicating normal capacity for exocytosis. To identify molecular targets
      implicated in the altered metabolism secretion coupling, DNA microarray analysis
      was performed on PDX1-deficient and control islets. Of the 2640 detected
      transcripts, 70 were up-regulated and 56 were down-regulated. Transcripts were
      subdivided into 12 clusters; the most prevalent were associated with metabolism.
      Quantitative reverse transcriptase-PCR confirmed increases in succinate
      dehydrogenase and ATP synthase mRNAs as well as pyruvate carboxylase and the
      transcript for the malate shuttle. In parallel there was a 50% reduction in mRNA
      levels for the mitochondrially encoded nd1 gene, a subunit of the NADH
      dehydrogenase comprising complex I of the mitochondrial respiratory chain. As a
      consequence, total cellular ATP concentration was drastically decreased by 75%,
      and glucose failed to augment cytosolic ATP, explaining the blunted glucose
      stimulated insulin secretion. Rotenone, an inhibitor of complex I, mimicked this
      effect. Surprisingly, TFAM, a nuclear-encoded transcription factor important for
      sustaining expression of mitochondrial genes, was down-regulated in islets
      expressing DN79PDX1. In conclusion, loss of PDX1 function alters expression of
      mitochondrially encoded genes through regulation of TFAM leading to impaired
      insulin secretion.

PMID- 15151994
TI  - Inter-alpha-trypsin inhibitor, a covalent protein-glycosaminoglycan-protein
      complex.

PMID- 15151995
TI  - Hydrophobic residues of the autotransporter EspP linker domain are important for
      outer membrane translocation of its passenger.
AB  - The autotransporter family of proteins is an important class of Gram-negative
      secreted virulence factors. Their secretion mechanism comprises entry to the
      periplasm via the Sec apparatus, followed by formation of an outer membrane beta
      barrel, which allows the N-terminal passenger domain to pass to the extracellular
      space. Several groups have identified a region immediately upstream of the beta
      domain that is important for outer membrane translocation, the so-called linker
      region. Here we characterize this region in EspP, a prototype of the serine
      protease autotransporters of enterobacteriaceae. We hypothesized that the folding
      of this region would be important in the outer membrane translocation process. We
      tested this hypothesis using a mutagenesis approach in conjunction with a series
      of nested deletions and found that in the absence of a complete passenger,
      mutations to the C-terminal helix, but not the upstream linker, significantly
      decrease secretion efficiency. However, in the presence of the passenger
      mutations to the amino-terminal region of the linker decrease secretion
      efficiency. Moreover, amino acids of hydrophobic character play a crucial role in
      linker function, suggesting the existence of a hydrophobic core or hydrophobic
      interaction necessary for outer membrane translocation of autotransporter
      proteins.

PMID- 15151997
TI  - Agonist-dependent and agonist-independent transactivations of the human
      constitutive androstane receptor are modulated by specific amino acid pairs.
AB  - The constitutive androstane receptor (CAR) is an interesting member of the
      nuclear receptor superfamily because of its exceptionally high constitutive
      activity due to ligand-independent interaction of the ligand-binding domain with
      co-activator proteins. This study compares the agonist-dependent and agonist
      independent activities of human CAR with those of mouse CAR and the vitamin D
      receptor and demonstrates that the constitutive activity of CAR is mediated by at
      least three contacts between the amino acids of helix 12, partner amino acids in
      helices 4 and 11, and a charge clamp between helices 12 and 3. The stabilization
      of helix 12 by a contact between its C terminus and the lysine of helix 4 has the
      same impact in human and mouse CARs. In addition, the charge clamp between the
      glutamate in helix 12 and the lysine in helix 3 is also important for the
      constitutive activity of both receptor orthologs but less critical for the
      agonist-dependent stabilization of their respective helices 12. Interestingly,
      Cys-357 in mouse CAR has significantly more impact on the stabilization of helix
      12 than does the orthologous position Cys-347 in human CAR. This deficit appears
      to be compensated by a more dominant role of Ile-330 in human CAR over Leu-340 in
      mouse CAR because it is more efficient than Cys-347 in controlling the
      flexibility of helix 12 in the presence of an agonist. The constitutive activity
      of other members of the nuclear receptor superfamily could be explained by a
      homologous hydrophobic interaction between large, non-polar amino acids of
      helices 11 and 12.

PMID- 15151996
TI  - Co-aggregation of FcgammaRII with FcepsilonRI on human mast cells inhibits
      antigen-induced secretion and involves SHIP-Grb2-Dok complexes.
AB  - Signaling through the high affinity IgE receptor FcepsilonRI on human basophils
      and rodent mast cells is decreased by co-aggregating these receptors to the low
      affinity IgG receptor FcgammaRII. We used a recently described fusion protein,
      GE2, which is composed of key portions of the human gamma1 and the human epsilon
      heavy chains, to dissect the mechanisms that lead to human mast cell and basophil
      inhibition through co-aggregation of FcgammaRII and FcepsilonRI. Unstimulated
      human mast cells derived from umbilical cord blood express the immunoreceptor
      tyrosine-based inhibitory motif-containing receptor FcgammaRII but not FcgammaRI
      or FcgammaRIII. Interaction of the mast cells with GE2 alone did not cause
      degranulation. Co-aggregating FcepsilonRI and FcgammaRII with GE2 1)
      significantly inhibited IgE-mediated histamine release, cytokine production, and
      Ca(2+) mobilization, 2) reduced the antigen-induced morphological changes
      associated with mast cell degranulation, 3) reduced the tyrosine phosphorylation
      of several cellular substrates, and 4) increased the tyrosine phosphorylation of
      the adapter protein downstream of kinase 1 (p62(dok); Dok), growth factor
      receptor-bound protein 2 (Grb2), and SH2 domain containing inositol 5-phosphatase
      (SHIP). Tyrosine phosphorylation of Dok was associated with increased binding to
      Grb2. Surprisingly, in non-stimulated cells, there were complexes of
      phosphorylated SHIP-Grb2-Dok that were lost upon IgE receptor activation but
      retained under conditions of Fcepsilon-Fcgamma co-aggregation. Finally, studies
      using mast cells from Dok-1 knock-out mice showed that IgE alone triggers
      degranulation supporting an inhibitory role for Dok degranulation. Our results
      demonstrate how human FcepsilonRI-mediated responses can be inhibited by co
      aggregation with FcgammaRIIB and implicate Dok, SHIP, and Grb2 as key
      intermediates in regulating antigen-induced mediator release.

PMID- 15151998
TI  - Hepatocyte growth factor-induced ectodomain shedding of cell adhesion molecule
      L1: role of the L1 cytoplasmic domain.
AB  - The L1 cell adhesion molecule and its soluble form are tumor-associated proteins
      and potential markers for tumor staging as well as targets for therapeutic
      intervention. Soluble L1 is produced by metalloprotease-mediated ectodomain
      shedding of L1. We investigated effects of hepatocyte growth factor (HGF), a
      growth factor shown to increase invasiveness of renal carcinoma cells, on
      ectodomain shedding of L1 from these cells. All of the tested L1-positive renal
      carcinoma cell lines released a 180-kDa form of L1 into the medium. In the
      presence of serum, addition of HGF led to a dose-dependent increase in L1
      shedding with a maximum reached at 5 ng/ml. In contrast, L1 shedding was
      inhibited by glial cell line-derived neurotrophic factor (GDNF). The tyrosine
      kinase inhibitor Genistein reduced basal and HGF-stimulated L1 shedding,
      indicating that protein phosphorylation is involved. To investigate the role of
      the L1 intracellular domain, two mutants of the L1 cytoplasmic part were
      constructed. L1trun lacking the complete intracellular domain showed enhanced
      basal shedding. In a L1YH mutant, containing the mutation tyrosine 1229 to
      histidine that deletes the ankyrin binding motif of L1, basal shedding was
      reduced. Disruption of actin assembly by cytochalasin D also reduced shedding of
      L1. These results indicate that the cytoplasmic domain regulates basal shedding
      of L1, and association with the cytoskeleton through the L1 ankyrin binding site
      is involved. HGF stimulated L1 shedding in both mutants, indicating that receptor
      mediated phosphorylation in the L1 cytoplasmic domain is not required for HGF
      stimulated shedding.

PMID- 15151999
TI  - Membrane topology of system xc- light subunit reveals a re-entrant loop with
      substrate-restricted accessibility.
AB  - Heteromeric amino acid transporters are composed of a heavy and a light subunit
      linked by a disulfide bridge. 4F2hc/xCT elicits sodium-independent exchange of
      anionic L-cysteine and L-glutamate (system x(c)(-)). Based on the accessibility
      of single cysteines to 3-(N-maleimidylpropionyl)biocytin, we propose a
      topological model for xCT of 12 transmembrane domains with the N and C termini
      located inside the cell. This location of N and C termini was confirmed by
      immunofluorescence. Studies of biotinylation and accessibility to sulfhydryl
      reagents revealed a re-entrant loop within intracellular loops 2 and 3. Residues
      His(110) and Thr(112), facing outside, are located at the apex of the re-entrant
      loop. Biotinylation of H110C was blocked by xCT substrates, by the
      nontransportable inhibitor (S)-4-carboxyphenylglycine, and by the impermeable
      reagent (2-sulfonatoethyl) methanethiosulfonate, which produced an inactivation
      of H110C that was protected by L-glutamate and L-cysteine with an IC(50) similar
      to the K(m). Protection was temperatureindependent. The data indicate that
      His(110) may lie close to the substrate binding/permeation pathway of xCT. The
      membrane topology of xCT could serve as a model for other light subunits of
      heteromeric amino acid transporters.

PMID- 15152000
TI  - Molecular dissection of Na+ binding to thrombin.
AB  - Na(+) binding near the primary specificity pocket of thrombin promotes the
      procoagulant, prothrombotic, and signaling functions of the enzyme. The effect is
      mediated allosterically by a communication between the Na(+) site and regions
      involved in substrate recognition. Using a panel of 78 Ala mutants of thrombin,
      we have mapped the allosteric core of residues that are energetically linked to
      Na(+) binding. These residues are Asp-189, Glu-217, Asp-222, and Tyr-225, all in
      close proximity to the bound Na(+). Among these residues, Asp-189 shares with Asp
      221 the important function of transducing Na(+) binding into enhanced catalytic
      activity. None of the residues of exosite I, exosite II, or the 60-loop plays a
      significant role in Na(+) binding and allosteric transduction. X-ray crystal
      structures of the Na(+)-free (slow) and Na(+)-bound (fast) forms of thrombin,
      free or bound to the active site inhibitor H-d-Phe-Pro-Arg-chloromethyl-ketone,
      document the conformational changes induced by Na(+) binding. The slow --> fast
      transition results in formation of the Arg-187:Asp-222 ion pair, optimal
      orientation of Asp-189 and Ser-195 for substrate binding, and a significant shift
      of the side chain of Glu-192 linked to a rearrangement of the network of water
      molecules that connect the bound Na(+) to Ser-195 in the active site. The changes
      in the water network and the allosteric core explain the thermodynamic signatures
      linked to Na(+) binding and the mechanism of thrombin activation by Na(+). The
      role of the water network uncovered in this study establishes a new paradigm for
      the allosteric regulation of thrombin and other Na(+)-activated enzymes involved
      in blood coagulation and the immune response.

PMID- 15152002
TI  - Activation and proteasomal degradation of rho GTPases by cytotoxic necrotizing
      factor-1 elicit a controlled inflammatory response.
AB  - The CNF1 toxin is produced by uropathogenic and meningitis-causing Escherichia
      coli. CNF1 penetrates autonomously into cells and confers phagocytic properties
      to epithelial and endothelial cells. CNF1 acts at the molecular level by
      constitutively activating Rho GTPases attenuated by their cellular ubiquitin
      mediated proteasomal degradation. Here we report the relationship between the
      ubiquitin-mediated proteasomal degradation of activated Rho and the endothelial
      cell response to the toxin. The type of cellular response to CNF1 intoxication,
      first screened by DNA microarray analysis, revealed the launching of a program
      oriented toward an inflammatory response. Parallel to Rho protein activation by
      CNF1, we also established the kinetics of production of monocyte chemotactic
      protein-1 (MCP-1), interleukin-8 (IL-8), IL-6, monocyte inflammatory protein
      3alpha (MIP-3alpha) and E-selectin. Both the mutation of the catalytic domain of
      the toxin (CNF1-C866S) and the inhibition of Rho proteins abrogate the CNF1
      induced production of the immunomodulators MIP-3alpha, MCP-1, and IL-8. These
      immunomodulators are also produced upon activation of Cdc42 and Rac
      preferentially. Our results indicate that, in addition to pathogen molecular
      pattern recognition by host-receptors, a direct activation of Rho proteins by the
      CNF1 virulence factor efficiently triggers a cellular reaction of host alert.
      Consistently, we assume that the CNF1-induced ubiquitin-mediated proteasomal
      degradation of activated Rho proteins may limit the amplitude of the host cell
      immune responses.

PMID- 15152001
TI  - Novel oligosaccharide side chains of the collagen-like region of BclA, the major
      glycoprotein of the Bacillus anthracis exosporium.
AB  - Spores of Bacillus anthracis, the causative agent of anthrax, are enclosed by a
      prominent loose fitting layer called the exosporium. The exosporium consists of a
      basal layer and an external hairlike nap. The filaments of the nap are composed
      of a highly immunogenic glycoprotein called BclA, which has a long, central
      collagen-like region with multiple XXG repeats. Most of the triplet repeats are
      PTG, and nearly all of the triplet repeats contain a threonine residue, providing
      multiple potential sites for O-glycosylation. In this study, we demonstrated that
      two O-linked oligosaccharides, a 715-Da tetrasaccharide and a 324-Da
      disaccharide, are released from spore- and exosporium-associated BclA by
      hydrazinolysis. Each oligosaccharide is probably attached to BclA through a
      GalNAc linker, which was lost during oligosaccharide release. We found that
      multiple copies of the tetrasaccharide are linked to the collagen-like region of
      BclA, whereas the disaccharide may be attached outside of this region. Using NMR,
      mass spectrometry, and other analytical techniques, we determined that the
      structure of the tetrasaccharide is 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6
      dideoxy-beta-d-glucopyranosyl-(1-->3)-alpha-l-rhamnopyranosyl-(1-->3)-alpha-l
      rhamnopyranosyl-(1-->2)-l-rhamnopyranose. The previously undescribed nonreducing
      terminal sugar (i.e. 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-d
      glucose) was given the trivial name anthrose. Anthrose was not found in spores of
      either Bacillus cereus or Bacillus thuringiensis, two species that are the most
      phylogenetically similar to B. anthracis. Thus, anthrose may be useful for
      species-specific detection of B. anthracis spores or as a new target for
      therapeutic intervention.

PMID- 15152003
TI  - A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O
      methyltransferase domain by ribavirin 5'-triphosphate.
AB  - Ribavirin is one of the few nucleoside analogues currently used in the clinic to
      treat RNA virus infections, but its mechanism of action remains poorly understood
      at the molecular level. Here, we show that ribavirin 5'-triphosphate inhibits the
      activity of the dengue virus 2'-O-methyltransferase NS5 domain (NS5MTase(DV)).
      Along with several other guanosine 5'-triphosphate analogues such as acyclovir, 5
      ethynyl-1-beta-d-ribofuranosylimidazole-4-carboxamide (EICAR), and a series of
      ribose-modified ribavirin analogues, ribavirin 5'-triphosphate competes with GTP
      to bind to NS5MTase(DV). A structural view of the binding of ribavirin 5'
      triphosphate to this enzyme was obtained by determining the crystal structure of
      a ternary complex consisting of NS5MTase(DV), ribavirin 5'-triphosphate, and S
      adenosyl-l-homocysteine at a resolution of 2.6 A. These detailed atomic
      interactions provide the first structural insights into the inhibition of a viral
      enzyme by ribavirin 5'-triphosphate, as well as the basis for rational drug
      design of antiviral agents with improved specificity against the emerging
      flaviviruses.

PMID- 15152004
TI  - Oxidative DNA damage associated with combination of guanine and superoxide
      radicals and repair mechanisms via radical trapping.
AB  - In living tissues under inflammatory conditions, superoxide radicals (O(2)*)) are
      generated and are known to cause oxidative DNA damage. However, the mechanisms of
      action are poorly understood. It is shown here that the combination of O(2)* with
      guanine neutral radicals, G(-H)* in single- or double-stranded
      oligodeoxyribonucleotides (rate constant of 4.7 +/- 1.0 x 10(8) m(-1) s(-1) in
      both cases), culminates in the formation of oxidatively modified guanine bases
      (major product, imidazolone; minor product, 8-oxo-7,8-dihydroguanine). The G(-H)*
      and O(2)* radicals were generated by intense 308 nm excimer laser pulses
      resulting in the one-electron oxidation and deprotonation of guanine in the 5'
      d(CC[2AP]-TCGCTACC) strands and the trapping of the ejected electrons by
      molecular oxygen (Shafirovich, V., Dourandin, A., Huang, W., Luneva, N. P., and
      Geacintov, N. E. (2000) Phys. Chem. Chem. Phys. 2, 4399-4408). The addition of
      Cu,Zn-superoxide dismutase, known to react rapidly with superoxide, dramatically
      enhances the life-times of guanine radicals from 4 to 7 ms to 0.2-0.6 s in the
      presence of 5 microm superoxide dismutase. Oxygen-18 isotope labeling experiments
      reveal two pathways of 8-oxo-7,8-dihydroguanine formation including either
      addition of O(2)* to the C-8 position of G(-H)* (in the presence of oxygen), or
      the hydration of G(-H)* (in the absence of oxygen). The formation of the guanine
      lesions via combination of guanine and superoxide radicals is greatly reduced in
      the presence of typical antioxidants such as trolox and catechol that rapidly
      regenerate guanine by the reductive "repair" of G(-H)* radicals. The mechanistic
      aspects of the radical reactions that either regenerate undamaged guanine in DNA
      or lead to oxidatively modified guanine bases are discussed.

PMID- 15152005
TI  - Appropriate function of 11beta-hydroxysteroid dehydrogenase type 1 in the
      endoplasmic reticulum lumen is dependent on its N-terminal region sharing similar
      topological determinants with 50-kDa esterase.
AB  - By interconverting glucocorticoids, 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1) exerts an important pre-receptor function and is currently
      considered a promising therapeutic target. In addition, 11beta-HSD1 plays a
      potential role in 7-ketocholesterol metabolism. Here we investigated the role of
      the N-terminal region on enzymatic activity and addressed the relevance of 11beta
      HSD1 orientation into the endoplasmic reticulum (ER) lumen. Previous studies
      revealed that the luminal orientation of 11beta-HSD1 and 50-kDa
      esterase/arylacetamide deacetylase (E3) is determined by their highly similar N
      terminal transmembrane domains. Substitution of Lys(5) by Ser in 11beta-HSD1, but
      not of the analogous Lys(4) by Ile in E3, led to an inverted topology in the ER
      membrane, indicating the existence of a second topological determinant. Here we
      identified Glu(25)/Glu(26) in 11beta-HSD1 and Asp(25) in E3 as the second
      determinant for luminal orientation. Our results suggest that the exact location
      of specific residues rather than net charge distribution on either side of the
      helix is critical for membrane topology. Analysis of charged residues in the N
      terminal domain revealed an essential role of Lys(35)/Lys(36) and Glu(25)/Glu(26)
      on enzymatic activity, suggesting that these residues are responsible for the
      observed stabilizing effect of the N-terminal membrane anchor on the catalytic
      domain of 11beta-HSD1. Moreover, activity measurements in intact cells expressing
      wild-type 11beta-HSD1, facing the ER lumen, or mutant K5S/K6S, facing the
      cytoplasm, revealed that the luminal orientation is essential for efficient
      oxidation of cortisol. Furthermore, we demonstrate that 11beta-HSD1, but not
      mutant K5S/K6S with cytoplasmic orientation, catalyzes the oxoreduction of 7
      ketocholesterol. 11beta-HSD1 and E3 constructs with cytosolic orientation of
      their catalytic moiety should prove useful in future studies addressing the
      physiological function of these proteins.

PMID- 15152006
TI  - Human immunodeficiency virus type 1 Gag assembly through assembly intermediates.
AB  - Human immunodeficiency virus Gag protein self-assembles into spherical particles,
      and recent reports suggest the formation of assembly intermediates during the
      process. To understand the nature of such assembly intermediates along with the
      mechanism of Gag assembly, we employed expression in Escherichia coli and an in
      vitro assembly reaction. When E. coli expression was performed at 37 degrees C,
      Gag predominantly assembled to a high order of multimer, apparently equivalent to
      the virus-like particles obtained following Gag expression in eukaryotic cells,
      through the formation of low orders of multimer characterized with a discreet
      sedimentation value of 60 S. Electron microscopy confirmed the presence of
      spherical particles in the E. coli cells. In contrast, expression at 30 degrees C
      resulted in the production of only the 60 S form of Gag multimer, and crescent
      shaped structures or small patches with double electron-dense layers were
      accumulated, but no complete particles. In vitro assembly reactions using
      purified Gag protein, when performed at 37 degrees C, also produced the high
      order of Gag multimers with some 60 S multimers, whereas the 30 degrees C
      reaction produced only the 60 S multimers. However, when the 60 S multimers were
      cross-linked so as not to allow conformational changes, in vitro assembly
      reactions at 37 degrees C did not produce any higher order of multimers. ATP
      depletion did not halt Gag assembly in the E. coli cells, and the addition of
      GroEL-GroES to in vitro reactions did not facilitate Gag assembly, indicating
      that conformational changes rather than protein refolding by chaperonins, induced
      at 37 degrees C, were solely responsible for the Gag assembly observed here. We
      suggest that Gag assembles to a capsid through the formation of the 60 S
      multimer, possibly a key intermediate of the assembly process, accompanied with
      conformational changes in Gag.

PMID- 15152007
TI  - Mutants in a small heat shock protein that affect the oligomeric state. Analysis
      and allele-specific suppression.
AB  - Oligomerization is an essential property of small heat shock proteins (sHSPs)
      that appears to regulate their chaperone activity. We have examined the role of
      conserved hydrophobic residues that are postulated to stabilize sHSP oligomers.
      We identified a mutation of Synechocystis Hsp16.6 that impairs function in vivo
      and in vitro. The V143A mutation is in the C-terminal extension, a region
      predicted to form an oligomeric interaction with a hydrophobic region that
      includes the site of a previously characterized mutation, L66A. Both mutants were
      dimeric, but V143A had a stronger oligomerization defect than L66A. However,
      V143A protected a model substrate better than L66A. This suggests that although
      the two regions both play a role in oligomerization, they are not equivalent.
      Nevertheless, the addition of either dimeric sHSP enhanced the in vitro chaperone
      activity of wild type Hsp16.6, consistent with models that the sHSP dimers
      initiate interactions with substrates. Suppressor analysis of V143A identified
      mutations in the N terminus that restored activity by restabilizing the oligomer.
      These mutants were allele-specific and unable to suppress L66A, although they
      suppressed a dimeric C-terminal truncation of Hsp16.6. Conversely, suppressors of
      L66A were unable to suppress either V143A or the truncation, although they, like
      suppressors of V143A, stabilize the Hsp16.6 oligomer. We interpret these data as
      evidence that the mutations V143A and L66A stabilize two different dimeric
      structures and as further support that sHSP dimers are active species.

PMID- 15152008
TI  - A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic
      reticulum-associated acyl-CoA:lysocardiolipin acyltransferase (ALCAT1) in mouse.
AB  - Cardiolipin is a major membrane polyglycerophospholipid that is required for the
      reconstituted activity of a number of key mitochondrial enzymes involved in
      energy metabolism. Cardiolipin is subjected to remodeling subsequent to its de
      novo biosynthesis to attain appropriate acyl composition for its biological
      functions. Yet, the enzyme(s) involved in the remodeling process have not been
      identified. We report here the identification and characterization of a murine
      gene that encodes an acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1).
      Expression of the ALCAT1 cDNA in either insect or mammalian cells led to a
      significant increase in acyl-CoA:monolysocardiolipin acyltransferase and acyl
      CoA: dilysocardiolipin acyltransferase activities that exhibited a dependence
      upon ALCAT1 enzyme levels. The recombinant ALCAT1 enzyme recognizes both
      monolysocardiolipin and dilysocardiolipin as substrates with a preference for
      linoleoyl-CoA and oleoyl-CoA as acyl donors. In contrast, no significant
      increases in acyltransferase activities by the recombinant ALCAT1 were detected
      against either glycerol-3-phosphate or a variety of other lysophospholipids as
      substrates, including lysophosphatidylcholine, lysophosphatidylethanolamine, and
      lysophosphatidylserine. Immunocytohistochemical analysis showed that the ALCAT1
      enzyme is localized in the endoplasmic reticulum, which is supported by a
      significant ALCAT activity in isolated liver and heart microsomes. Northern blot
      analysis indicates that the mouse ALCAT1 is widely distributed, with the highest
      expression in heart and liver. In support of a role for ALCAT1 in maintaining
      heart function, the ALCAT1 gene is conserved among different species of
      vertebrates, but not in non-atrium organisms. ALCAT1 represents the first
      identified cardiolipin-remodeling enzyme from any living organism; its
      identification implies a novel role for the endoplasmic reticulum in cardiolipin
      metabolism.

PMID- 15152009
TI  - Expression of a dominant negative heat shock factor-1 construct inhibits
      aneuploidy in prostate carcinoma cells.
AB  - Recent studies have implicated heat shock proteins (HSP) and heat shock
      transcription factor 1 (HSF1) in tumor progression. We have examined the role of
      HSF1 in the malignant phenotype of PC-3 prostate carcinoma cells. We have
      developed a dominant negative construct of HSF1 that antagonizes transcription
      from HSP promoters and results in the depletion of intracellular HSP 70. Our
      studies indicate that expression of DN-HSF1 dramatically alters the DNA content
      of PC-3 cells (derived from p53 null prostatic carcinoma) and inhibits aneuploidy
      in these cells. This effect is due to prolonged expression of DN-HSF1, and
      transient expression of the dominant negative factor from an inducible promoter
      failed to cause the effect. Inhibition of aneuploidy in p53 null PC-3 cells by DN
      HSF1 expression was recapitulated by expression within the cells of wild type
      p53. Furthermore, cells expressing DN-HSF1 showed a profound inhibition in the
      development of aneuploidy when exposed to chemical agents that disrupt the
      mitotic spindle and prevent progression through metaphase. Inhibition of
      aneuploidy in PC-3 cells expressing DN-HSF1 was associated with delayed breakdown
      of cyclin B1 compared with controls, consistent with a role for wild type HSF1 in
      the regulation of cyclin B1 degradation, a key step in the control of mitosis.
      Our experiments therefore demonstrate that HSF1 plays a functional role in cancer
      cells under nonstress conditions and influences cell cycle behavior and
      progression through mitosis and promotes the development of the aneuploid state.

PMID- 15152011
TI  - Proteome analysis associated with cadmium adaptation in U937 cells:
      identification of calbindin-D28k as a secondary cadmium-responsive protein that
      confers resistance to cadmium-induced apoptosis.
AB  - Cadmium is a well known environmental toxicant and carcinogen. To identify
      proteins involved in cellular adaptive responses to cadmium, we established
      cadmium-adapted U937 cells that exhibit resistance to cadmium-induced apoptosis,
      and we performed comparative proteome analysis of these cells with parental cells
      that were either untreated or treated with cadmium. Newly identified proteins
      that were changed in expression level in both adapted cells and cadmium-treated
      parental cells included proteins implicated in cell proliferation and malignant
      transformation. Most interesting, a calcium-binding protein calbindin-D(28k) was
      increased only in the adapted cells but not in cadmium-exposed parental cells.
      The level of calbindin-D(28k) increased by the degree of cadmium adaptation and
      was stably maintained without selective pressure of cadmium. Cadmium-adapted U937
      cells were resistant to the toxic effects of cytosolic calcium rise by cadmium
      treatment and by depletion of intracellular calcium stores, suggesting that
      enhanced calcium buffering by up-regulated calbindin-D(28k) may be responsible
      for acquiring resistance to cadmium-induced apoptosis. We demonstrated that
      overexpression of calbindin-D(28k) in MN9D neuronal cells resulted in reduced
      cadmium-induced apoptosis. Our study documents for the first time that cells
      respond to long term cadmium exposure by increasing calbindin-D(28k) expression,
      thereby attenuating cadmium-induced apoptosis.

PMID- 15152013
TI  - Spike patterning by Ca2+-dependent regulation of a muscarinic cation current in
      entorhinal cortex layer II neurons.
AB  - In entorhinal cortex layer II neurons, muscarinic receptor activation promotes
      depolarization via activation of a nonspecific cation current (I(NCM)). Under
      muscarinic influence, these neurons also develop changes in excitability that
      result in activity-dependent induction of delayed firing and bursting activity.
      To identify the membrane processes underlying these phenomena, we examined
      whether I(NCM) may undergo activity-dependent regulation. Our voltage-clamp
      experiments revealed that appropriate depolarizing protocols increased the basal
      level of inward current activated during muscarinic stimulation and suggested
      that this effect was due to I(NCM) upregulation. In the presence of low buffering
      for intracellular Ca(2+), this upregulation was transient, and its decay could be
      followed by a phase of I(NCM) downregulation. Both up- and downregulation were
      elicited by depolarizing stimuli able to activate voltage-gated Ca(2+) channels
      (VGCC); both were sensitive to increasing concentrations of intracellular Ca(2+)
      chelating agents with downregulation being abolished at lower Ca(2+)-buffering
      capacities; both were reduced or suppressed by VGCC block or in the absence of
      extracellular Ca(2+). These data indicate that relatively small increases in
      [Ca(2+)](i) driven by firing activity can induce upregulation of a basal
      muscarinic depolarizing-current level, whereas more pronounced [Ca(2+)](i)
      elevations can result in I(NCM) downregulation. We propose that the interaction
      of activity-dependent positive and negative feedback mechanisms on I(NCM) allows
      entorhinal cortex layer II neurons to exhibit emergent properties, such as
      delayed firing and enhanced or suppressed responses to repeated stimuli, that may
      be of importance in the memory functions of the temporal lobe and in the
      pathophysiology of epilepsy.

PMID- 15152014
TI  - Impact of rearing conditions and short-term light exposure on signaling
      performance in Drosophila photoreceptors.
AB  - The amount of visual information an animal can extract from its environment is
      ultimately limited by the signaling performance of its photoreceptors. To
      maximize their performance, photoreceptors must be able to accommodate large
      changes in input caused by the dynamic properties of the visual environment and
      the animal's own behavior. This is likely to require a range of adaptation
      mechanisms operating over multiple time scales. Using intracellular recordings,
      we investigated the effects of developmental light rearing conditions and the
      effects of 2 h light or dark exposure prior the experiment on the signaling
      performance of adult Drosophila melanogaster photoreceptors. We show that light
      rearing amplifies photoreceptors' voltage responses to light contrast changes by
      >or =20% and accelerates them by 3 ms. We argue that these differences mostly
      reflect changes in the timing of the early phototransduction reactions, some of
      which are persistent. However, being born and nurtured in certain lighting
      conditions does not set an ultimate limit for the signaling performance of
      Drosophila photoreceptors. Two-hour light exposure prior to the experiment can
      improve the information capacity of dark-reared photoreceptors close to the
      values of light-reared photoreceptors by reducing voltage noise. This effect may
      originate from plastic changes in the utilization of phototransduction proteins
      and ion channels.

PMID- 15152012
TI  - The importance of a critical protonation state and the fate of the catalytic
      steps in class A beta-lactamases and penicillin-binding proteins.
AB  - Beta-lactamases and penicillin-binding proteins are bacterial enzymes involved in
      antibiotic resistance to beta-lactam antibiotics and biosynthetic assembly of
      cell wall, respectively. Members of these large families of enzymes all
      experience acylation by their respective substrates at an active site serine as
      the first step in their catalytic activities. A Ser-X-X-Lys sequence motif is
      seen in all these proteins, and crystal structures demonstrate that the side
      chain functions of the serine and lysine are in contact with one another. Three
      independent methods were used in this report to address the question of the
      protonation state of this important lysine (Lys-73) in the TEM-1 beta-lactamase
      from Escherichia coli. These techniques included perturbation of the pK(a) of Lys
      73 by the study of the gamma-thialysine-73 variant and the attendant kinetic
      analyses, investigation of the protonation state by titration of specifically
      labeled proteins by nuclear magnetic resonance, and by computational treatment
      using the thermodynamic integration method. All three methods indicated that the
      pK(a) of Lys-73 of this enzyme is attenuated to 8.0-8.5. It is argued herein that
      the unique ground-state ion pair of Glu-166 and Lys-73 of class A beta-lactamases
      has actually raised the pK(a) of the active site lysine to 8.0-8.5 from that of
      the parental penicillin-binding protein. Whereas we cannot rule out that Glu-166
      might activate the active site water, which in turn promotes Ser-70 for the
      acylation event, such as proposed earlier, we would like to propose as a
      plausible alternative for the acylation step the possibility that the ion pair
      would reconfigure to the protonated Glu-166 and unprotonated Lys-73. As such,
      unprotonated Lys-73 could promote serine for acylation, a process that should be
      shared among all active-site serine beta-lactamases and penicillin-binding
      proteins.

PMID- 15152015
TI  - Topographic representation of odorant molecular features in the rat olfactory
      bulb.
AB  - Individual glomeruli in the mammalian olfactory bulb (OB) most probably represent
      a single odorant receptor (OR). The assembly of glomeruli thus forms the maps of
      ORs. How is the approximately 1,000 ORs represented spatially in the glomerular
      map? Using the method of optical imaging of intrinsic signals and systematic
      panels of stimulus odorants, we recorded odorant-induced glomerular activity from
      the dorsal and dorsolateral areas of the rat OB, and examined the molecular
      receptive range (MRR) of individual glomeruli. We then deduced the characteristic
      molecular features that were shared by odorants effective in activating
      individual glomeruli. Analysis of the spatial representation of the MRR showed
      that glomeruli with similar MRRs gathered in close proximity and formed molecular
      feature clusters and subclusters. Although the shape of the clusters varied among
      different OBs, the clusters were arranged at stereotypical positions in relation
      to the zonal organization of the OB. Examination of the spatial representation of
      the characteristic molecular features of odorants using structurally semirigid
      aromatic compounds suggest a systematic and gradual change in the characteristic
      molecular features according to the position of subclusters in the map. The
      topographic map of the characteristic molecular features may reflect a systematic
      spatial representation of the ORs and may participate in the neural bases for the
      odorant structure-odor quality relationship.

PMID- 15152017
TI  - Differences between accumbens core and shell neurons exhibiting phasic firing
      patterns related to drug-seeking behavior during a discriminative-stimulus task.
AB  - The habit-forming effects of abused drugs depend on the mesocorticolimbic
      dopamine system innervating the nucleus accumbens (NAcc). To examine whether
      different NAcc subterritories (core and medial shell) exhibit a differential
      distribution of neurons showing phasic firing patterns correlated with drug
      seeking behavior, rats were trained to self-administer cocaine, and activity of
      single NAcc neurons was recorded. In the presence of a discriminative-stimulus
      (S(D)) tone, a single lever press produced an intravenous infusion of cocaine
      (0.35 mg/kg), terminated the tone, and started an intertone interval ranging from
      3 to 6 min. Lever presses during this intertone interval had no programmed
      consequences. In addition to evaluating neuronal firing patterns associated with
      cocaine-reinforced presses, we also evaluated firing patterns associated with
      unreinforced lever presses to allow interpretation of firing free of factors
      other than the instrumental response (such as tone-off and onset of the pump
      signaling drug infusion). Core neurons exhibited a greater change in firing than
      medial shell neurons both in the seconds preceding the reinforced and
      unreinforced lever press response and in the seconds following the unreinforced
      response. Core and medial shell neurons exhibited similar changes in firing
      during the seconds following the cocaine-reinforced press. The differential
      distribution of neurons exhibiting phasic changes in firing preceding the lever
      press suggests that the physiological activity of core neurons may play a greater
      role than that of medial shell neurons in processes related to the execution of
      conditioned drug-seeking responses.

PMID- 15152016
TI  - Single pulse stimulation of the human subthalamic nucleus facilitates the motor
      cortex at short intervals.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective
      treatment for Parkinson's disease (PD). The mechanism is poorly understood. High
      frequency STN DBS has been reported to affect motor cortex excitability in a
      complex way, but the timing between STN stimuli and changes in motor cortical
      (M1) excitability has not been investigated. We examined the time course of
      changes in motor cortical excitability following single pulse STN DBS. We studied
      14 PD patients with implanted DBS electrodes in the STN, 2 patients with
      electrodes in internal globus pallidus (GPi), and 1 patient with an electrode in
      the sensory thalamus. Transcranial magnetic stimulation (TMS) was delivered to
      the M1 ipsilateral to the DBS with induced currents either in the anterior
      posterior direction in the brain to evoke indirect (I) waves or in the lateral
      medial direction to activate corticospinal axons directly. Single pulse
      stimulation through the DBS contacts preceded the TMS by 0-10 ms. Surface EMG was
      recorded from the contralateral first dorsal interosseous muscle. Three
      milliseconds after STN stimulation, the motor evoked potential (MEP) amplitudes
      produced by anterior-posterior current were significantly larger than control
      responses, while the responses to lateral-medial currents were unchanged. Similar
      facilitation also occurred after GPi stimulation, but not with thalamic
      stimulation. Single pulse STN stimulation facilitates the M1 at short latencies.
      The possible mechanisms include antidromic excitation of the cortico-STN fibers
      or transmission through the basal ganglia-thalamocortical pathway.

PMID- 15152018
TI  - Large-scale organization of ferret auditory cortex revealed using continuous
      acquisition of intrinsic optical signals.
AB  - We have adapted a new approach for intrinsic optical imaging, in which images
      were acquired continuously while stimuli were delivered in a series of
      continually repeated sequences, to provide the first demonstration of the large
      scale tonotopic organization of both primary and nonprimary areas of the ferret
      auditory cortex. Optical responses were collected during continuous stimulation
      by repeated sequences of sounds with varying frequency. The optical signal was
      averaged as a function of time during the sequence, to produce reflectance
      modulation functions (RMFs). We examined the stability and properties of the RMFs
      and show that their zero-crossing points provide the best temporal reference
      points for quantifying the relationship between the stimulus parameter values and
      optical responses. Sequences of different duration and direction of frequency
      change gave rise to comparable results, although in some cases discrepancies were
      observed, mostly between upward- and downward-frequency sequences. We
      demonstrated frequency maps, consistent with previous data, in primary auditory
      cortex and in the anterior auditory field, which were verified with
      electrophysiological recordings. In addition to these tonotopic gradients, we
      demonstrated at least 2 new acoustically responsive areas on the anterior and
      posterior ectosylvian gyri, which have not previously been described. Although
      responsive to pure tones, these areas exhibit less tonotopic order than the
      primary fields.

PMID- 15152019
TI  - Viral delivery of NR2D subunits reduces Mg2+ block of NMDA receptor and restores
      NT-3-induced potentiation of AMPA-kainate responses in maturing rat motoneurons.
AB  - N-methyl-D-aspartate (NMDA) responsiveness of motoneurons declines during the
      initial 2 postnatal weeks due to increasing Mg2+ block of NMDA receptors. Using
      gene chip analyses, RT-PCR, and immunochemistry, we have shown that the NR2D
      subunit of the NMDA receptor (NMDAR), known to confer resistance to Mg2+ block,
      also declines in motoneurons during this period. We injected a viral construct
      (HSVnr2d) into the lumbar spinal cord on postnatal day 2 in an attempt to restore
      NMDAR function in motoneurons during the second postnatal week. Following HSVnr2d
      injection, we detected elevated levels of NR2D mRNA in spinal cord samples and
      NR2D protein specifically in motoneurons. These molecular changes were associated
      with marked functional alterations whereby NMDAR-mediated responses in
      motoneurons associated with both dorsal root (DR) and ventrolateral funiculus
      (VLF) inputs returned to values observed at E18 due to decreased Mg2+ blockade.
      Viruses carrying the beta-galactosidase gene did not induce these effects. NT-3
      is known to potentiate AMPA-kainate responses in motoneurons if the response has
      an NMDAR-mediated component and thus is normally ineffective during the second
      postnatal week. Restoration of NMDAR-mediated responsiveness in the second
      postnatal week was accompanied by a return of the ability of neurotrophin-3 (NT
      3) to potentiate the AMPA-kainate responses produced by both DR and VLF synaptic
      inputs. We conclude that delivery of the gene for a specific NMDA subunit can
      restore properties characteristic of younger animals to spinal cord motoneurons.
      This approach might be useful for enhancing the function of fibers surviving in
      the damaged spinal cord.

PMID- 15152020
TI  - Proton modulation of alpha 1 beta 3 delta GABAA receptor channel gating and
      desensitization.
AB  - Alphabetagamma GABA(A) receptor currents are phasic and desensitizing, whereas
      alphabetadelta GABA(A) receptor currents are tonic and have no fast
      desensitization. alphabetagamma receptors are subsynaptic and mediate phasic
      inhibition, whereas alphabetadelta receptors are extra- or perisynaptic and
      mediate tonic inhibition. Given the different roles of these GABA(A) receptor
      isoforms and the fact that GABA(A) receptors are allosterically regulated by
      extracellular pH in a subunit-dependent manner, we compared the effects of
      changing pH on rat delta or gamma2L subunit-containing GABA(A) receptor currents.
      Human embryonic kidney cells (HEK293T) were transfected with cDNAs encoding rat
      alpha1, beta3, gamma2L, or delta GABA(A) receptor subunits in several binary and
      ternary combinations, and whole cell and single channel patch-clamp recordings
      were obtained. Lowering pH substantially enhanced alpha1beta3 receptor currents.
      This effect was significantly more pronounced for ternary alpha1beta3delta
      receptors, whereas ternary alpha1beta3gamma2L receptors were relatively
      insensitive to lowered pH. Lowering pH did not affect the extent of
      desensitization of alpha1beta3 and alpha1beta3gamma2L receptor currents, but
      significantly increased the extent of desensitization of alpha1beta3delta
      receptor currents. Lowering pH prolonged deactivation of alpha1beta3 and
      alpha1beta3delta receptor currents and enhanced the "steady-state" currents of
      alpha1beta3delta receptors evoked by long-duration (28 s) GABA applications.
      Lowering pH significantly increased mean open duration of alpha1beta3delta steady
      state single channel currents due to introduction of a longer-duration open
      state, suggesting that low pH enhances alpha1beta3delta receptor steady-state
      currents by modifying GABA(A) receptor gating properties.

PMID- 15152022
TI  - Medial perforant path inhibition mediated by mGluR7 is reduced after status
      epilepticus.
AB  - Metabotropic glutamate receptor (mGluR)-mediated inhibition within the dentate
      gyrus is altered after epilepsy. Whether these changes occur during the
      developmental period of the disease (i.e., the latent period) has not yet been
      investigated. Field excitatory postsynaptic potentials (fEPSPs) were recorded in
      the lateral (LPP) and medial perforant path (MPP) simultaneously in adult mouse
      hippocampal slices 3-9 days after pilocarpine (PILO)-induced status epilepticus.
      Genetically manipulated mice (mGluR8 knockout and mGluR4/8 double knockout) and
      pharmacologically selective agonists were used to identify specific mGluR
      subtypes affected after PILO. Pharmacological activation of mGluR7 by L-AP4 in
      both wild-type and mGluR4/8 double knockout mice selectively reduced fEPSPs in
      the MPP, but not LPP, and this level of inhibition was significantly reduced 3-9
      days after PILO-induced SE. Activation of mGluR2/3 reversibly depressed the fEPSP
      slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8
      activation selectively inhibited evoked responses in the LPP, but not in the MPP,
      and this level of inhibition did not change after PILO treatment. These data
      suggest that reduced presynaptic inhibition mediated by mGluR7, but not mGluR2/3
      or mGluR8, may play a role during the latent period in generating
      hyperexcitability in the dentate and thereby contribute to epileptogenesis.

PMID- 15152021
TI  - Excitation of cerebellar interneurons by group I metabotropic glutamate
      receptors.
AB  - Cerebellar basket and stellate neurons (BSNs) provide feed-forward inhibition to
      Purkinje neurons (PNs) and thereby play a principal role in determining the
      output of the cerebellar cortex. During low-frequency transmission, glutamate
      released at parallel fiber synapses excites BSNs by binding to AMPA receptors;
      high-frequency transmission also recruits N-methyl-d-aspartate (NMDA) receptors.
      We find that, in addition to these ligand-gated receptors, a G-protein-coupled
      glutamate receptor subtype participates in exciting BSNs. Stimulation of
      metabotropic glutamate receptor 1alpha (mGluR1alpha) with the mGluR agonist (RS)
      3,5-dihydroxyphenylglycine (DHPG) leads to an increase in spontaneous firing of
      BSNs and indirectly to an increase in the frequency of spontaneous inhibitory
      postsynaptic currents (sIPSCs) recorded in PNs. Under conditions in which ligand
      gated glutamate receptors are blocked, parallel fiber stimulation generates a
      slow excitatory postsynaptic current (EPSC) in BSNs that is inhibited by
      mGluR1alpha-selective antagonists. This slow EPSC is capable of increasing BSN
      spiking and indirectly increasing sIPSCs frequency in PNs. Our findings reinforce
      the idea that distinct subtypes of glutamate receptors are activated in response
      to different patterns of activity at excitatory synapses. The results also raise
      the possibility that mGluR1alpha-dependent forms of synaptic plasticity may occur
      at excitatory inputs to BSNs.

PMID- 15152023
TI  - Neural basis for the hyperalgesic action of cholecystokinin in the rostral
      ventromedial medulla.
AB  - The analgesic actions of opioids can be modified by endogenous "anti-opioid"
      peptides, among them cholecystokinin (CCK). CCK is now thought to have a broader,
      pronociceptive role, and contributes to hyperalgesia in inflammatory and
      neuropathic pain states. The aim of this study was to determine whether anti
      opioid and pronociceptive actions of CCK have a common underlying mechanism. We
      showed previously that a low dose of CCK microinjected into the rostral
      ventromedial medulla (RVM) blocked the analgesic effect of systemically
      administered morphine by preventing activation of off-cells, which are the
      antinociceptive output of this well characterized pain-modulating region. At this
      anti-opioid dose, CCK had no effect on the spontaneous activity of these neurons
      or on the activity of on-cells (hypothesized to facilitate nociception) or
      "neutral cells" (which have no known role in pain modulation). In this study, we
      used microinjection of a higher dose of CCK into the RVM to test whether
      activation of on-cells could explain the pronociceptive action of this peptide.
      Paw withdrawal latencies to noxious heat and the activity of a characterized RVM
      neuron were recorded in rats lightly anesthetized with methohexital. CCK (30
      ng/200 nl) activated on-cells selectively and produced behavioral hyperalgesia.
      Firing of off-cells and neutral cells was unaffected. These data show that
      direct, selective activation of RVM on-cells by CCK is sufficient to produce
      thermal hyperalgesia and indicate that the anti-opioid and pronociceptive effects
      of this peptide are mediated by actions on different RVM cell classes.

PMID- 15152024
TI  - Cholinergic modulation of the locomotor network in the lamprey spinal cord.
AB  - Acetylcholine (ACh) was found here to be a strong modulator of swimming activity
      in the isolated spinal cord preparation of the adult lamprey (Ichthyomyzon
      unicuspis). During fictive swimming induced with either D-glutamate or N-methyl-D
      aspartate, addition of ACh (200 microM) significantly reduced the cycle period of
      ventral root bursts to 54%, intersegmental phase lag to 32%, and ventral root
      burst proportion to 80% of control levels. Effects of ACh were apparent at
      concentrations as low as 1 microM. Both nicotinic and muscarinic receptors are
      involved, in that application of either nicotinic or muscarinic agonists alone
      significantly reduced cycle period. There is sufficient endogenous ACh in the
      spinal cord to modulate ongoing fictive swimming, as shown by application of the
      cholinesterase inhibitor eserine (physostigmine). Eserine (20 microM)
      significantly reduced the cycle period to 78% and phase lag to 58% of control
      levels, and these effects were reversed with the addition of cholinergic
      blockers. Addition of only a nicotinic or muscarinic antagonist, mecamylamine (10
      microM) or scopolamine (20 microM), respectively, to the spinal cord during
      fictive swimming produced significant increases in cycle period and phase lag,
      suggesting that both types of cholinergic receptors participate in endogenous
      cholinergic modulation. It is concluded that ACh is an endogenous modulator of
      the locomotor network in the lamprey spinal cord and that ACh may take part in
      the regulation of cycle period, intersegmental coupling, and ventral root burst
      duration.

PMID- 15152025
TI  - Neurons in monkey prefrontal cortex whose activity tracks the progress of a three
      step self-ordered task.
AB  - The self-ordered task is a powerful tool for the analysis of dorsal prefrontal
      deficits. Each trial consists of a number of steps, and subjects must remember
      their choices in previous steps. The task becomes more difficult as the number of
      objects to be remembered increases. We recorded the activity of 156 neurons in
      the mid-dorsal prefrontal cortex of two rhesus monkeys performing an oculomotor
      version of the task. Although the task requires working memory, there was no
      convincing evidence for activity selective for the working memory of the objects
      that the monkey had to remember. Instead, nearly one-half of neurons (47%,
      74/156) showed activity that was modulated according to the step of the task in
      any one or more task periods. Although the monkey's reward also increased with
      step, the neurons exhibited little or no step modulation in a reward control task
      in which reward increased without a concurrent increase in task difficulty. The
      activity of some neurons was also selective for the location of saccade target
      that the monkey voluntarily chose. Neurons showed less step modulation in error
      trials, and there was no increase between the second and third step responses on
      trials in which the error was on the third step. These results suggest that the
      mid-dorsal prefrontal cortex contributes to the self-ordered task, not by
      providing an object working memory signal, but by regulating some general aspect
      of the performance in the difficult task.

PMID- 15152026
TI  - Inhibition of bladder activity by 5-hydroxytryptamine1 serotonin receptor
      agonists in cats with chronic spinal cord injury.
AB  - The serotonin (5-hydroxytryptamine1A) 5-HT1A receptor agonist 8-OH-DPAT [(R)- (+)
      8-hydroxy-2-(di-n-propylamino)tetralin] inhibits bladder activity under
      nociceptive but not innocuous conditions in cats with an intact spinal cord,
      suggestive of an effect on primary afferent C fibers or their targets. Because C
      fibers play a key role in reflex micturition in chronic spinal cord injury (SCI),
      we investigated the effect of 8-OH-DPAT on micturition in SCI cats. We also
      investigated GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4
      methoxybenzyl)acrylamide), which has agonist activity predominantly at 5-HT1B and
      5-HT1D receptors but also at the 5-HT1A receptor. Chloralose-anesthetized cats
      were catheterized through the bladder dome for saline-filling cystometry. Dose
      response curves for i.v. 8-OH-DPAT (0.3-30 microg/kg) and GR-46611 (0.03-300
      microg/kg) were followed in three cases each by 5-HT1A antagonist WAY-100635 [N
      tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide] at 300
      microg/kg. Threshold volume, capacity, residual volume, micturition volume, and
      arterial pressure were measured. Intact cats showed few significant changes in
      cystometric variables. SCI cats responded to both 8-OH-DPAT and GR-46611 with
      dose-dependent increases in threshold volume, capacity, and residual volume,
      significant at > or =10 microg/kg for 8-OH-DPAT and at > or =3 microg/kg for GR
      46611. Effects of 8-OH-DPAT but not GR-46611 were largely reversed by WAY-100635.
      Both 5-HT1A and 5-HT1B/1D agonists may offer a promising means of reducing
      bladder hyperactivity and increasing bladder capacity in patients with chronic
      SCI.

PMID- 15152027
TI  - Regulation of rat hepatocyte function by P2Y receptors: focus on control of
      glycogen phosphorylase and cyclic AMP by 2-methylthioadenosine 5'-diphosphate.
AB  - Hepatocyte function is regulated by several P2Y receptor subtypes. Here we report
      that 2-methylthioadenosine 5'-diphosphate (2-MeSADP), an agonist at P2Y(1),
      P2Y(12), and P2Y(13) receptors, potently (threshold 30 nM) stimulates glycogen
      phosphorylase in freshly isolated rat hepatocytes. Antagonism by N(6)-methyl 2'
      deoxyadenosine 3',5'-bisphosphate (MRS 2179) confirms that this response is
      mediated by P2Y(1) receptors. In addition, in these cells, both 2-MeSADP and UTP
      inhibited glucagon-stimulated cyclic AMP accumulation. This inhibitory effect of
      2-MeSADP was not reversed by the P2Y(1) antagonists, adenosine-3'-phosphate-5'
      phosphate (A3P5P) or MRS 2179, both in the range 1 to 300 microM, indicating that
      it was not mediated by P2Y(1) receptors. This contrasts with the increase in
      cytosolic free Ca(2+) concentration ([Ca(2+)](c)) induced by 2-MeSADP, which has
      shown to be inhibited by A3P5P. Pertussis toxin abolished the inhibitory effect
      of both UTP and 2-MeSADP. After culture of cells for 48 h, the ability of 2
      MeSADP to inhibit cyclic AMP accumulation was greatly diminished. Reverse
      transcriptase-polymerase chain reaction analysis revealed that during this
      culture period, there was a decline in the ability to detect transcripts for
      P2Y(12) and P2Y(13) receptors, both of which are activated by 2-MeSADP and
      negatively coupled to adenylyl cyclase. However, in freshly isolated cells, the
      P2Y(12) and P2Y(13) receptor antagonist, 2-propylthio-beta,gamma
      dichloromethylene-d-ATP (AR-C67085) (10 nM to 300 microM) did not alter the
      ability of 2-MeSADP to inhibit glucagon-stimulated cyclic AMP accumulation. We
      conclude that 2-MeSADP regulates rat hepatocyte glycogen phosphorylase by acting
      on P2Y(1) receptors coupled to raised [Ca(2+)](c), and by inhibiting cyclic AMP
      levels by an unknown G(i)-coupled receptor subtype, distinct from P2Y(1),
      P2Y(12), or P2Y(13) receptors.

PMID- 15152028
TI  - Antiallodynic effects of loperamide and fentanyl against topical capsaicin
      induced allodynia in unanesthetized primates.
AB  - Capsaicin produces thermal allodynia in animals and humans by acting as an
      agonist at vanilloid receptor subtype 1 [VR1; also known as transient receptor
      potential vanilloid type 1 (TRPV1)]. VR1 receptors are widely distributed in the
      periphery (e.g., on primary afferent neurons). These studies examined the ability
      of loperamide (0.1-1 mg/kg s.c.; a micro-opioid agonist that is peripherally
      selective after systemic administration), in preventing and reversing thermal
      allodynia caused by topical capsaicin (0.004 M) in rhesus monkeys, within a tail
      withdrawal assay (n = 4; 38 degrees C and 42 degrees C; normally non-noxious
      thermal stimuli). The effects of loperamide were compared with those of the
      centrally penetrating micro-agonist, fentanyl (0.0032-0.032 mg/kg s.c.). We also
      characterized the allodynic effects of the endogenous VR1 agonist
      ("endovanilloid"), N-oleoyldopamine (OLDA; 0.0013-0.004 M). In this model,
      loperamide and fentanyl produced dose-dependent prevention of capsaicin-induced
      allodynia, whereas only fentanyl produced robust reversal of ongoing allodynia.
      Antagonism experiments with naltrexone (0.1 mg/kg s.c.) or its analog,
      methylnaltrexone (0.32 mg/kg s.c.), which does not readily cross the blood-brain
      barrier, suggest that the antiallodynic effects of loperamide and fentanyl were
      predominantly mediated by peripherally and centrally located micro-receptors,
      respectively. Loperamide and fentanyl (1 mg/kg and 0.032 mg/kg, respectively)
      also prevented OLDA (0.004 M)-induced allodynia. Up to the largest dose studied,
      loperamide was devoid of thermal antinociceptive effects at 48 degrees C (a
      noxious thermal stimulus, in the absence of capsaicin). By contrast, fentanyl
      (0.01-0.032 mg/kg) caused dose-dependent antinociception in this sensitive
      thermal antinociceptive assay (a presumed centrally mediated effect). These
      studies show that loperamide, acting as a peripherally selective micro-agonist
      after systemic administration, can prevent capsaicin-induced thermal allodynia in
      primates in vivo, in the absence of thermal antinociceptive effects.

PMID- 15152029
TI  - gamma-hydroxybutyrate increases a potassium current and decreases the H-current
      in hippocampal neurons via GABAB receptors.
AB  - gamma-Hydroxybutyrate (GHB) is used for the treatment of alcoholism and to induce
      absence seizures in animals, but it has also recently emerged as a drug of abuse.
      In hippocampal neurons, GHB may activate its own putative receptor as well as
      GABA(B) receptors to affect synaptic transmission. We used voltage-clamp
      recordings of rat CA1 pyramidal neurons to characterize the postsynaptic
      conductances affected by GHB and to further clarify the site of GHB action. Low
      concentrations of GHB (0.1-1 mM) did not affect postsynaptic properties, but 10
      mM GHB elicited an outward current at resting potential by augmenting an inwardly
      rectifying potassium current and concomitantly decreased the hyperpolarization
      activated H-current (I(h)). Like GHB, the selective GABA(B)-receptor agonist
      baclofen (20 microM) increased a potassium current and decreased I(h). In the
      presence of 10 mM GHB, the baclofen effects were largely occluded. The selective
      GABA(B) receptor antagonist CGP 55845 [3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino
      2-(S)-hydroxypropyl-p-benzyl-phosphinic acid] blocked the effects of both GHB and
      baclofen, whereas the putative GHB receptor antagonist NCS-382 [(2E)-(5-hydroxy
      5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid] was
      ineffective. The GHB and baclofen effects were prevented in the presence of 200
      microM barium, indicating that GHB augments a K(+) conductance, probably a G
      protein-coupled inwardly rectifying K(+) (GIRK) current. The decrease of I(h) by
      GHB and baclofen was also prevented by barium, suggesting that the diminution of
      I(h) is secondary to GIRK augmentation. Our results indicate that high GHB
      levels, which can be reached during abuse or intoxication, activate only GABA(B)
      receptors and not GHB receptors at the postsynaptic level to augment an inwardly
      rectifying K(+) current and decrease I(h).

PMID- 15152030
TI  - Purinergic and vanilloid receptor activation releases glutamate from separate
      cranial afferent terminals in nucleus tractus solitarius.
AB  - Vanilloid (VR1) and purinergic (P2X) receptors are found in cranial afferent
      neurons in nodose ganglia and their central terminations within the solitary
      tract nucleus (NTS), but little is known about their function. We mechanically
      dissociated dorsomedial NTS neurons to preserve attached native synapses and
      tested for VR1 and P2X function primarily in spindle-shaped neurons resembling
      intact second-order neurons. All neurons (n = 95) exhibited spontaneous glutamate
      (EPSCs) and GABA (IPSCs)-mediated synaptic currents. VR1 agonist capsaicin (CAP;
      100 nm) reversibly increased EPSC frequency, effects blocked by capsazepine. ATP
      (100 microm) increased EPSC frequency, actions blocked by P2X antagonist
      pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS; 20 microm). In all
      CAP-resistant neurons, P2X agonist alphabeta-methylene-ATP (alphabeta-m-ATP)
      increased EPSC frequency. Neither CAP nor alphabeta-m-ATP altered EPSC
      amplitudes, kinetics, or holding currents. Thus, activation of VR1 and P2X
      receptors selectively facilitated presynaptic glutamate release on different NTS
      neurons. PPADS and 2',3'-O-(2,4,6-trinitrophenyl)-ATP blocked alphabeta-m-ATP
      responses, but P2X1-selective antagonist NF023 (8,8'-[carbonylbis (imino-3,1
      phenylene carbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid) did not. The
      pharmacological profile and transient kinetics of ATP responses are consistent
      with P2X3 homomeric receptors. TTX and Cd(2+) did not eliminate agonist-evoked
      EPSC frequency increases, suggesting that voltage-gated sodium and calcium
      channels are not required. In nodose ganglia, CAP but not alphabeta-m-ATP evoked
      inward currents in slow conducting neurons and the converse pattern in
      myelinated, rapidly conducting neurons (n = 14). Together, results are consistent
      with segregation of glutamatergic terminals into either P2X sensitive or VR1
      sensitive that correspondingly identify myelinated and unmyelinated afferent
      pathways at the NTS.

PMID- 15152031
TI  - Contrasting roles of basolateral amygdala and orbitofrontal cortex in impulsive
      choice.
AB  - The orbitofrontal cortex (OFC) and basolateral nucleus of the amygdala (BLA)
      share many reciprocal connections, and a functional interaction between these
      regions is important in controlling goal-directed behavior. However, their
      relative roles have proved hard to dissociate. Although injury to these brain
      regions can cause similar effects, it has been suggested that the resulting
      impairments arise through damage to different, yet converging, cognitive
      processes. Patients with OFC or amygdala lesions exhibit maladaptive decision
      making and aberrant social behavior often described as impulsive. Impulsive
      choice may be measured in both humans and rodents by evaluating intolerance to
      delay of reinforcement. Rats with excitotoxic lesions of the BLA and OFC were
      tested on such a delay-discounting procedure. Although lesions of the BLA
      increased choice of the small immediate reward, indicating greater impulsivity,
      OFC lesions had the opposite effect, increasing preference for the larger but
      delayed reward. The fact that the delay did not devalue the large reward to such
      an extent in OFC-lesioned animals supports the suggestion that the OFC is
      involved in updating the incentive value of outcomes in response to devaluation.
      In contrast, the BLA-lesioned animals markedly decreased their preference for the
      large reward when it was delayed, potentially because of an inability to maintain
      a representation of the reward in its absence. This is the first time that
      lesions to these two structures have produced opposite behavioral effects,
      indicating their distinct contributions to cognition.

PMID- 15152032
TI  - Preferential effects of the metabotropic glutamate 2/3 receptor agonist LY379268
      on conditioned reinstatement versus primary reinforcement: comparison between
      cocaine and a potent conventional reinforcer.
AB  - Metabotropic glutamate receptors (mGluRs) have been implicated in regulating
      anxiety, stress responses, and the neurobehavioral effects of psychostimulants.
      The present study sought to determine whether group II mGluR activation by the
      potent mGlu2/3 receptor agonist, (-)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic
      acid (LY379268), antagonizes reinstatement of cocaine-seeking induced by cocaine
      related stimuli and whether this effect extends to behavior induced by stimuli
      conditioned to a potent conventional reinforcer, sweetened condensed milk (SCM).
      Also, we tested whether the suppressant effects of LY379268 on conditioned
      reinstatement extend to the primary reinforcing effects of cocaine or SCM. Rats
      were trained to associate discriminative stimuli (S(D)) with the availability of
      cocaine or SCM versus non-reward and then subjected to repeated extinction
      sessions during which the respective reinforcers and S(D) were withheld.
      Subsequent reexposure to the cocaine or SCM S(D), but not the non-reward S(D),
      produced recovery of responding at the previously active lever. LY379268 (0.3-3.0
      mg/kg, s.c.) dose-dependently attenuated recovery of cocaine seeking but reduced
      conditioned reinstatement by the SCM S(D) only at the highest dose. LY379268 did
      not alter responding reinforced directly by SCM, and only the highest LY379268
      dose reduced cocaine self-administration. The results suggest that the effects of
      LY379268 are selective for behavior maintained by cocaine as opposed to palatable
      conventional reinforcers. More importantly, the results show that LY379268
      suppresses behavior motivated by stimuli conditioned to cocaine or SCM more
      effectively than consummatory behavior maintained by the unconditioned effects of
      these substances. As such, the results identify group II mGluRs as a
      pharmacotherapeutic target for craving and relapse prevention associated with
      cocaine cue exposure.

PMID- 15152033
TI  - Block of AMPA receptor desensitization by a point mutation outside the ligand
      binding domain.
AB  - Desensitization of ionotropic glutamate receptors (GluRs), specifically the AMPA
      receptor subtype, shapes the postsynaptic response at certain synapses in the
      brain. All known mechanisms that alter desensitization, either pharmacological or
      mutational, are associated with the ligand-binding domain. Here we report that
      substitution of a conserved positively charged arginine (R) with a negatively
      charged glutamate in the linker between the pore-forming M3 segment and the S2
      lobe, a region outside the ligand-binding domain, blocks desensitization in
      homomeric AMPA receptors composed of GluR-B(i) subunits. A charge-reversing
      substitution of a glutamate adjacent to this conserved R enhanced
      desensitization, consistent with these effects attributable to electrostatics.
      Homologous substitutions of the conserved R in GluR-B(o), GluR-A(i) and the
      kainate receptor GluR-6 subunits produced comparable but less visible effects on
      desensitization. Subunit specificity was also apparent for accessibility of
      substituted cysteines in the M3-S2 linker, suggesting that this part of the
      channel is not structurally identical in different GluRs. Additionally,
      reactivity with a sulfhydryl-specific reagent was state dependent, suggesting
      that the conformations of the nonconducting closed and desensitized states are
      different at the level of the M3-S2 linker. Our results therefore represent the
      first identification of elements outside the ligand-binding domain affecting
      desensitization in non-NMDA receptor channels and suggest that electrostatic
      interactions involving charged residues in the M3-S2 linker influence channel
      gating in a subunit- and subtype-specific manner.

PMID- 15152034
TI  - Cholecystokinin modulates migration of gonadotropin-releasing hormone-1 neurons.
AB  - Expression of the brain-gut peptide cholecystokinin (CCK) in the developing
      olfactory-gonadotropin-releasing hormone-1 (GnRH-1) neuroendocrine systems was
      characterized, and the function of CCK in these systems was analyzed both in vivo
      and in vitro. We present novel data demonstrating that CCK transcript and protein
      are expressed in sensory cells in the developing olfactory epithelium and
      vomeronasal organ, with both ligand and receptors (CCK-1R and CCK-2R) found on
      olfactory axons throughout prenatal development. In addition, migrating GnRH-1
      neurons in nasal regions express CCK-1R but not CCK-2R receptors. The role of CCK
      in olfactory-GnRH-1 system development was evaluated using nasal explants, after
      assessing that the in vivo expression of both CCK and CCK receptors was mimicked
      in this in vitro model. Exogenous application of CCK (10(-7) m) reduced both
      olfactory axon outgrowth and migration of GnRH-1 cells. This inhibition was
      mediated by CCK-1R receptors. Moreover, CCK-1R but not CCK-2R antagonism caused a
      shift in the location of GnRH-1 neurons, increasing the distance that the cells
      migrated. GnRH-1 neuronal migration in mice carrying a genetic deletion of either
      CCK-1R or CCK-2R receptor genes was also analyzed. At embryonic day 14.5, the
      total number of GnRH-1 cells was identical in wild-type and mutant mice; however,
      the number of GnRH-1 neurons within forebrain was significantly greater in CCK-1R
      /- embryos, consistent with an accelerated migratory process. These results
      indicate that CCK provides an inhibitory influence on GnRH-1 neuronal migration,
      contributing to the appropriate entrance of these neuroendocrine cells into the
      brain, and thus represent the first report of a developmental role for CCK.

PMID- 15152035
TI  - Development of GABAergic and glycinergic transmission in the neonatal rat dorsal
      horn.
AB  - Cutaneous spinal sensory transmission appears to lack inhibitory control in the
      newborn spinal cord, but the properties of GABAergic and glycinergic synapses in
      the neonatal dorsal horn have not been characterized. Whole-cell patch-clamp
      recordings from rat superficial dorsal horn neurons in spinal cord slices at
      postnatal day 0 (P0) to P2, P6-P7, and P13-P14 revealed an age-dependent increase
      in the frequency of spontaneous IPSCs, which were abolished by the GABA(A)
      receptor (GABA(A)R) antagonist bicuculline between P0 and P7 but not at P14.
      GABA(A)R-mediated miniature IPSCs (mIPSCs), but not glycinergic mIPSCs, were
      present at birth, and GABA mIPSCs remained more frequent than glycine mIPSCs at
      all ages. Sciatic nerve stimulation resulted in IPSCs with both GABAergic and
      glycinergic components, although a larger contribution arose from GABA(A)
      receptors at all ages. In gramicidin perforated patch-clamp recordings, exogenous
      GABA applications produced depolarization in 40% of neurons at P0-P2, but the
      reversal potential of GABA-evoked currents (E(GABA)) was consistently more
      negative than action potential threshold at this age. By P6-P7, GABA evoked only
      membrane hyperpolarization. The GABA(B)R agonist baclofen elicited an outward
      current in all neurons with peak amplitudes observed by P6-P7 and abolished
      sciatic nerve-evoked monosynaptic glutamatergic EPSCs in all groups. The results
      show considerable postnatal development of inhibitory processing in the dorsal
      horn with GABAergic mechanisms initially dominant over glycinergic events.
      GABA(A)R-mediated depolarizations during the first postnatal week are likely to
      be important for the maturation of spinal networks but do not provide a major
      excitatory drive to the newborn dorsal horn.

PMID- 15152036
TI  - Independent functions of hsp90 in neurotransmitter release and in the continuous
      synaptic cycling of AMPA receptors.
AB  - The delivery of neurotransmitter receptors into synapses is essential for
      synaptic function and plasticity. In particular, AMPA-type glutamate receptors
      (AMPA receptors) reach excitatory synapses according to two distinct routes: a
      regulated pathway, which operates transiently during synaptic plasticity, and a
      constitutive pathway, which maintains synaptic function under conditions of basal
      transmission. However, the specific mechanisms that distinguish these two
      trafficking pathways are essentially unknown. Here, we evaluate the role of the
      molecular chaperone hsp90 (heat shock protein 90) in excitatory synaptic
      transmission in the hippocampus. On one hand, we found that hsp90 is necessary
      for the efficient neurotransmitter release at the presynaptic terminal. In
      addition, we identified hsp90 as a critical component of the cellular machinery
      that delivers AMPA receptors into the postsynaptic membrane. Using the hsp90
      specific inhibitors radicicol and geldanamycin, we show that hsp90 is required
      for the constitutive trafficking of AMPA receptors into synapses during their
      continuous cycling between synaptic and nonsynaptic sites. In contrast, hsp90
      function is not required for either the surface delivery of AMPA receptors into
      the nonsynaptic plasma membrane or for the acute, regulated delivery of AMPA
      receptors into synapses during plasticity induction (long-term potentiation). The
      synaptic cycling of AMPA receptors was also blocked by an hsp90-binding
      tetratricopeptide repeat (TPR) domain, suggesting that the role of hsp90 in AMPA
      receptor trafficking is mediated by a TPR domain-containing protein. These
      results demonstrate new roles for hsp90 in synaptic function by controlling
      neurotransmitter release and, independently, by mediating the continuous cycling
      of synaptic AMPA receptors.

PMID- 15152037
TI  - NR2B-containing receptors mediate cross talk among hippocampal synapses.
AB  - Under some conditions, synaptically released glutamate can exert long-range
      actions in the cortical microcircuitry. To what extent glutamate spillover leads
      to direct cross talk among individual synapses remains unclear. We recorded NMDAR
      mediated EPSCs in acute hippocampal slices at 35 degrees C by stimulating two
      independent pathways that converge on the same CA1 pyramidal cell. Activation of
      a conditioning pathway in the presence of the use-dependent blocker dizocilpine
      maleate (MK801) resulted in partial NMDA receptor (NMDAR) blockade in the other,
      silent pathway. This was accompanied by an increase in the rise time of the EPSCs
      in the conditioning (although not the silent) pathway, implying an increase in
      diffusional distance from release site to NMDARs. We estimated that up to
      approximately 30% of NMDARs contributing to EPSCs were activated by glutamate
      released from multiple synaptic sources; however, NMDAR-mediated synaptic cross
      talk was undetectable when NR2B subunit-containing receptors were blocked (but
      could be rescued by blocking glutamate uptake). We propose that NR2B-containing
      NMDARs can detect glutamate arising from multiple synapses, whereas NR2A
      containing NMDARs only normally mediate direct synaptic transmission. These NMDAR
      isoforms thus play complementary roles in sensing global and local glutamate
      signals, respectively.

PMID- 15152038
TI  - Castration restores function and neurofilament alterations of aged symptomatic
      males in a transgenic mouse model of spinal and bulbar muscular atrophy.
AB  - Transgenic models of neurodegenerative disease have proved uniquely powerful for
      delineating pathways of neuronal dysfunction and cell death. We have developed a
      transgenic model of the polyglutamine disease spinal and bulbar muscular atrophy
      (SBMA), an adult-onset, slowly progressive motor neuron disease caused by
      polyglutamine expansion in the androgen receptor (AR). Mice bearing a human AR
      with 112 glutamines reproduce many aspects of SBMA, including slowly progressive,
      gender-specific motor deficits, and neuronal intranuclear inclusions. Despite
      substantial motor deficits in male AR112Q mice, no motor neuron loss was
      observed, indicating that neuronal dysfunction, rather than neuronal death, is
      central to disease. Moreover, reduced levels of unphosphorylated neurofilament
      heavy chain (NF-H) were observed in motor neurons, suggesting a role for NF-H in
      SBMA neuronal dysfunction. The elimination of androgens by surgical castration of
      severely affected, aged 112Q male mice partially restored motor function as well
      as NF-H levels. These data suggest that hormone-based therapies designed to treat
      SBMA patients, even with advanced disease, are likely to be effective.

PMID- 15152039
TI  - Memory reconsolidation and extinction have distinct temporal and biochemical
      signatures.
AB  - Memory retrieval is not a passive phenomenon. Instead, it triggers a number of
      processes that either reinforce or alter stored information. Retrieval is thought
      to activate a second memory consolidation cascade (reconsolidation) that requires
      protein synthesis. Here, we show that the temporal dynamics of memory
      reconsolidation are dependent on the strength and age of the memory, such that
      younger and weaker memories are more easily reconsolidated than older and
      stronger memories. We also report that reconsolidation and extinction, two
      opposing processes triggered by memory retrieval, have distinct biochemical
      signatures: pharmacological antagonism of either cannabinoid receptor 1 or L-type
      voltage-gated calcium channels blocks extinction but not reconsolidation. These
      studies demonstrate the dynamic nature of memory processing after retrieval and
      represent a first step toward a molecular dissection of underlying mechanisms.

PMID- 15152040
TI  - Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in
      amygdala-dependent fear conditioning.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase
      receptor B (TrkB), play a critical role in activity-dependent synaptic plasticity
      and have been implicated as mediators of hippocampal-dependent learning and
      memory. The present study is the first to demonstrate a role for BDNF and TrkB in
      amygdala-dependent learning. Here, the use of Pavlovian fear conditioning as a
      learning model allows us to examine the concise role of BDNF in the amygdala
      after a single learning session and within a well understood neural circuit.
      Using in situ hybridization, mRNA levels of six different trophic factors [BDNF,
      neurotrophin (NT) 4/5, NGF, NT3, aFGF, and bFGF) were measured at varying time
      points during the consolidation period after fear conditioning. We found
      temporally specific changes only in BDNF gene expression in the basolateral
      amygdala after paired stimuli that supported learning but not after exposure to
      neutral or aversive stimuli alone. Using Western blotting, we found that the Trk
      receptor undergoes increased phosphorylation during this consolidation period,
      suggesting an activation of the receptor subsequent to BDNF release. Furthermore,
      disruption of neurotrophin signaling with intra-amygdala infusion of the Trk
      receptor antagonist K252a disrupted acquisition of fear conditioning. To address
      the specific role of the TrkB receptor, we created a novel lentiviral vector
      expressing a dominant-negative TrkB isoform (TrkB.T1), which specifically blocked
      TrkB activation in vitro. In vivo, TrkB.T1 lentivirus blocked fear acquisition
      without disrupting baseline startle or expression of fear. These data suggest
      that BDNF signaling through TrkB receptors in the amygdala is required for the
      acquisition of conditioned fear.

PMID- 15152041
TI  - Serotonergic regulation of membrane potential in developing rat prefrontal
      cortex: coordinated expression of 5-hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7
      receptors.
AB  - The developing prefrontal cortex receives a dense serotonergic innervation, yet
      little is known about the actions of serotonin [5-Hydroxytryptamine (5-HT)] in
      this region during development. Here, we examined the developmental regulation of
      5-HT receptors controlling the excitability of pyramidal neurons of this region.
      Using whole-cell recordings in in vitro brain slices, we identified a dramatic
      shift in the effects of 5-HT on membrane potential during the postnatal
      developmental period. In slices derived from young animals [postnatal day (P) 6
      to P19], administration of 5-HT elicits a robust depolarization of layer V
      pyramidal neurons, which gradually shifts to a hyperpolarization commencing
      during the third postnatal week. This progression is the result of coordinated
      changes in the function of 5-HT7 and 5-HT2A receptors, which mediate different
      aspects of the depolarization, and of 5-HT1A receptors, which signal the late
      developing hyperpolarization. The loss of the 5-HT7 receptor-mediated
      depolarization and the appearance of the 5-HT1A receptor-mediated
      hyperpolarization appears to reflect changes in receptor expression. In contrast,
      the decline in the 5-HT2A receptor depolarization with increasing age was
      associated with changes in the effectiveness with which these receptors could
      elicit a membrane depolarization, rather than loss of the receptors per se.
      Together, these results outline coordinated changes in the serotonergic
      regulation of cortical excitability at a time of extensive synaptic development
      and thus suggest a key role for these receptor subtypes in the postnatal
      development of the prefrontal cortex.

PMID- 15152042
TI  - Burst initiation and termination in phasic vasopressin cells of the rat
      supraoptic nucleus: a combined mathematical, electrical, and calcium fluorescence
      study.
AB  - Vasopressin secreting neurons of the rat hypothalamus discharge lengthy,
      repeating bursts of action potentials in response to physiological stress.
      Although many electrical currents and calcium-dependent processes have been
      isolated and analyzed in these cells, their interactions are less well fathomed.
      In particular, the mechanism of how each burst is triggered, sustained, and
      terminated is poorly understood. We present a mathematical model for the bursting
      mechanism, and we support our model with new simultaneous electrical recording
      and calcium imaging data. We show that bursts can be initiated by spike-dependent
      calcium influx, and we propose that the resulting elevation of bulk calcium
      inhibits a persistent potassium current. This inhibition depolarizes the cell
      above threshold and so triggers regenerative spiking and further calcium influx.
      We present imaging data to show that bulk calcium reaches a plateau within the
      first few seconds of the burst, and our model indicates that this plateau occurs
      when calcium influx is balanced by efflux and uptake into stores. We conjecture
      that the burst is terminated by a slow, progressive desensitization to calcium of
      the potassium leak current. Finally, we propose that the opioid dynorphin, which
      is known to be secreted from the somatodendritic region and has been shown
      previously to regulate burst length and phasic activity in these cells, is the
      autocrine messenger for this desensitization.

PMID- 15152043
TI  - Altered sodium channel expression in second-order spinal sensory neurons
      contributes to pain after peripheral nerve injury.
AB  - Peripheral nerve injury is known to upregulate the rapidly repriming Na(v)1.3
      sodium channel within first-order spinal sensory neurons. In this study, we
      hypothesized that (1) after peripheral nerve injury, second-order dorsal horn
      neurons abnormally express Na(v)1.3, which (2) contributes to the responsiveness
      of these dorsal horn neurons and to pain-related behaviors. To test these
      hypotheses, adult rats underwent chronic constriction injury (CCI) of the sciatic
      nerve. Ten days after CCI, allodynia and hyperalgesia were evident. In situ
      hybridization, quantitative reverse transcription-PCR, and immunocytochemical
      analysis revealed upregulation of Na(v)1.3 in dorsal horn nociceptive neurons but
      not in astrocytes or microglia, and unit recordings demonstrated
      hyperresponsiveness of dorsal horn sensory neurons. Intrathecal antisense
      oligodeoxynucleotides targeting Na(v)1.3 decreased the expression of Na(v)1.3
      mRNA and protein, reduced the hyperresponsiveness of dorsal horn neurons, and
      attenuated pain-related behaviors after CCI, all of which returned after
      cessation of antisense delivery. These results demonstrate for the first time
      that sodium channel expression is altered within higher-order spinal sensory
      neurons after peripheral nerve injury and suggest a link between misexpression of
      the Na(v)1.3 sodium channel and central mechanisms that contribute to neuropathic
      pain after peripheral nerve injury.

PMID- 15152044
TI  - Acceleration of visual system development by environmental enrichment.
AB  - Thus far, the developmental plasticity of the visual system has been studied by
      altering or reducing visual experience. Here, we investigated whether a complex
      sensory-motor stimulation, provided by rearing animals in an enriched
      environment, affects visual system development. We found that raising mice in
      this condition causes an earlier eye opening, a precocious development of visual
      acuity, and an accelerated decline of white matter-induced long-term
      potentiation. These effects are accompanied by a precocious cAMP response element
      mediated gene expression and a significant increase of BDNF protein and GAD65/67
      expression in enriched pups. In addition, we showed that enriched pups
      experienced higher levels of licking behavior provided by adult females. Thus,
      rearing mice from birth in an enriched environment leads to a conspicuous
      acceleration of visual system development as ascertained at behavioral,
      electrophysiological, and molecular level.

PMID- 15152045
TI  - Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine
      receptor 3.
AB  - T-cells play an important role in controlling viral infections inside the CNS. To
      study the role of the chemokine receptor CXCR3 in the migration and positioning
      of virus-specific effector T-cells within the brain, CXCR3-deficient mice were
      infected intracerebrally with lymphocytic choriomeningitis virus (LCMV). Analysis
      of the induction phase of the antiviral CD8+ T-cell response did not reveal any
      immune defects in CXCR3-deficient mice. Yet, when mice were challenged with LCMV
      intracerebrally, most CXCR3-deficient mice survived the infection, whereas wild
      type mice invariably died from CD8+ T-cell-mediated immunopathology. Quantitative
      analysis of the cellular infiltrate in CSF of infected mice revealed modest, if
      any, decrease in the number of mononuclear cells recruited to the meninges in the
      absence of CXCR3. However, immunohistological analysis disclosed a striking
      impairment of CD8+ T-cells from CXCR3-deficient mice to migrate from the meninges
      into the outer layers of the brain parenchyma despite similar localization of
      virus-infected target cells. Reconstitution of CXCR3-deficient mice with wild
      type CD8+ T-cells completely restored susceptibility to LCMV-induced meningitis.
      Thus, taken together, our results strongly point to a critical role for CXCR3 in
      the positioning of effector T-cells at sites of viral inflammation in the brain.

PMID- 15152046
TI  - Extracellular signal-regulated protein kinase activation is required for
      metabotropic glutamate receptor-dependent long-term depression in hippocampal
      area CA1.
AB  - Activation of group 1 metabotropic glutamate receptors (mGluRs) induces long-term
      depression (LTD) of synaptic transmission that relies on dendritic protein
      synthesis. We investigated the signal transduction pathways required for mGluR
      LTD to identify candidate mechanisms for mGluR regulation of synaptic protein
      synthesis. Our results demonstrate a role for extracellular signal-regulated
      protein kinase (ERK), a subclass of the mitogen-activated protein kinases
      (MAPKs), in mGluR-LTD in area CA1 of the rat hippocampus. Inhibitors of the
      upstream kinase of ERK, MAP/ERK kinase significantly reduce mGluR-LTD induced by
      the group 1 agonist dihydroxyphenylglycine (DHPG) and synaptic stimulation but do
      not affect NMDA receptor-dependent LTD. In contrast, inhibitors of p38 MAPK were
      ineffective against DHPG-induced LTD. Consistent with the role of ERK in mGluR
      LTD, we observed that DHPG treatment of hippocampal slices (isolated CA1), at
      concentrations that induce LTD, results in a robust phosphorylation of ERK but
      not of p38 MAPK. These results point to ERK as an important regulator of mGluR
      LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis.

PMID- 15152047
TI  - Group I metabotropic glutamate receptors inhibit GABA release at interneuron
      Purkinje cell synapses through endocannabinoid production.
AB  - Actions of endocannabinoids in the cerebellum can be demonstrated following
      distinct stimulation protocols in Purkinje cells. First, depolarization-induced
      elevations of intracellular Ca2+ lead to the suppression of neurotransmitter
      release from both inhibitory and excitatory afferents. In another case,
      postsynaptic group I metabotropic glutamate receptors (mGluRs) trigger a strong
      inhibition of the glutamatergic inputs from parallel and climbing fibers. Both
      pathways involve endocannabinoids retrogradely acting on type 1 cannabinoid
      receptors (CB1Rs) at presynaptic terminals. Here, we show that group I mGluR
      activation also depresses GABAergic transmission at the synapses between
      molecular layer interneurons and Purkinje cells. Using paired recordings, we
      found that application of the group I mGluR agonist (RS)-3,5
      dihydroxyphenylglycine reduced the evoked IPSCs in Purkinje cells. This effect
      was independent of postsynaptic Ca2+ increases and was completely blocked by a
      CB1R antagonist. Experiments performed with the GTP-analogues GDP-betaS and GTP
      gammaS provided evidence that endocannabinoids released after G-protein
      activation can also inhibit GABAergic inputs onto nearby, unstimulated Purkinje
      cells. Block of the enzymes DAG lipase or phospholipase C reduced the group I
      mGluR-dependent inhibition, suggesting that 2-arachidonyl glycerol could act as
      retrograde messenger. Finally, group I mGluR activation by brief bursts of
      activity of the parallel fibers induced a short-lived depression of spontaneous
      IPSCs via presynaptic CB1Rs. Our results reveal a mechanism with potential
      physiological importance, by which glutamatergic synapses induce an
      endocannabinoid-mediated inhibition of the GABAergic inputs onto Purkinje cells.

PMID- 15152048
TI  - Infection with an endemic human herpesvirus disrupts critical glial precursor
      cell properties.
AB  - Human herpesvirus 6 (HHV-6), a common resident virus of the human CNS, has been
      implicated in both acute and chronic inflammatory--demyelinating diseases.
      Although HHV-6 persists within the human CNS and has been described to infect
      mature oligodendrocytes, nothing is known about the susceptibility of glial
      precursors, the ancestors of myelin-producing oligodendrocytes, to viral
      infection. We show that HHV-6 infects human glial precursor cells in vitro.
      Active infection was demonstrated by both electron microscopy and expression of
      viral gene transcripts and proteins, with subsequent formation of cell syncytia.
      Infection leads to alterations in cell morphology and impairment of cell
      replication but not increased cell death. Infected cells showed decreased
      proliferation as measured by bromodeoxyuridine uptake, which was confirmed by
      blunting of the cell growth rate of infected cells compared with uninfected
      controls over time. The detailed analysis using novel, fluorescent-labeled HHV-6A
      or HHV-6B reagents demonstrated strong G1/S phase inhibition in infected
      precursor cells. Cell cycle arrest in HHV-6-infected cells was associated with a
      profound decrease in the expression of the glial progenitor cell marker A2B5 and
      a corresponding increase in the oligodendrocyte differentiation marker GalC.
      These data demonstrate for the first time that infection of primary human glial
      precursor cells with a neurologically relevant human herpesvirus causes profound
      alterations of critical precursor cell properties. In light of recent
      observations that repair of CNS demyelination is dependent on the generation of
      mature oligodendrocytes from the glial precursor cell pool, these findings may
      have broad implications for both the ineffective repair seen in demyelinating
      diseases and the disruption of normal glial maturation.

PMID- 15152049
TI  - Syntaxin-1A is excluded from recycling synaptic vesicles at nerve terminals.
AB  - At presynaptic terminals, intermixing during cycles of exocytosis and endocytosis
      challenges the molecular identity of the plasma and synaptic vesicle membranes.
      Although synaptic vesicle components are retrieved during recycling, the extent
      to which plasma membrane proteins enter the synaptic vesicle recycling pathway
      has not been examined. The target-SNARE (N-ethylmaleimide-sensitive factor
      attachment protein receptor) syntaxin-1 was shown previously to be present on
      putative synaptic vesicular membranes (Koh et al., 1993; Walch-Solimena et al.,
      1995; Kretzschmar et al., 1996), suggesting that syntaxin may cycle between the
      synaptic vesicle pool and the cell surface (Walch-Solimena et al., 1995). This
      implies that the molecular identity of the two membranes is not maintained during
      synaptic activity. Because the main role of syntaxin-1 is as a target-SNARE for
      vesicle fusion, appearance on synaptic vesicles could lead to futile interactions
      with vesicle-SNARE proteins. We investigated whether the subcellular localization
      of syntaxin-1A, tagged with the pH-sensitive fluorescent tag pHluorin, is
      regulated during neurotransmission using laser-scanning microscopy. We report
      here that syntaxin-1A is predominantly localized to the plasma membrane, with a
      small proportion present in an intracellular compartment with a lumenal pH
      consistent with synaptic vesicles. However, the internal fraction of syntaxin-1A
      is excluded from synaptic vesicles that undergo action potential-dependent
      recycling. These data indicate that the molecular identity of opposing exocytotic
      membranes is preserved by the sorting of syntaxin-1A from recycling synaptic
      vesicles.

PMID- 15152050
TI  - The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in
      protein processing.
AB  - The neuroligins are a family of postsynaptic transmembrane proteins that
      associate with presynaptic partners, the beta-neurexins. Neurexins and
      neuroligins play a critical role in initiating formation and differentiation of
      synaptic junctions. A recent study reported that a mutation of neuroligin-3
      (NL3), an X-linked gene, was found in siblings with autistic spectrum disorder in
      which two affected brothers had a point mutation that substituted a Cys for
      Arg451. To characterize the mutation at the biochemical level, we analyzed
      expression and activity of the mutated protein. Mass spectrometry comparison of
      the disulfide bonding pattern between the native and the mutated proteins
      indicates the absence of aberrant disulfide bonding, suggesting that the
      secondary structure of the mutated protein is conserved. However, the mutation
      separately affects protein expression and activity. The Cys mutation causes
      defective neuroligin trafficking, leading to retention of the protein in the
      endoplasmic reticulum. This, in turn, decreases the delivery of NL3 to the cell
      surface. Also, the small fraction of protein that reaches the cell membrane lacks
      or has markedly diminished beta-neurexin-1 (NX1beta) binding activity. Other
      substitutions for Arg451 allow for normal cellular expression but diminished
      affinity for NX1beta. Our findings reveal a cellular phenotype and loss of
      function for a congenital mutation associated with autistic spectrum disorders.

PMID- 15152052
TI  - Postnatal changes in cerebral oxygen extraction in the preterm infant are
      associated with intraventricular hemorrhage and hemorrhagic parenchymal
      infarction but not periventricular leukomalacia.
AB  - Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of
      acquired brain damage in babies born prematurely. This study examined the changes
      in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in
      25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral
      injury and 13 had acquired brain injury; cystic periventricular leukomalacia
      (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also
      had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5(th)-95(th)
      centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral
      injury were 0.38 (0.23-0.53) on d 1, 0.31 (0.18-0.45) on d 2, and 0.28 (0.17
      0.38) on d 3. Infants who developed cystic PVL had no significant change in
      cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE
      fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1
      to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral
      FOE values were seen in the two infants with HPI. The different patterns of
      change in cerebral FOE with HPI and cystic PVL provide additional evidence that
      the pathogenesis of these two conditions is different. Because high cerebral FOE
      is likely to be a consequence of low cerebral oxygen delivery, probably because
      of low cerebral blood flow, our results indicate that fluctuations in cerebral
      blood flow may occur when there is IVH or HPI.

PMID- 15152053
TI  - SARS: the first pandemic of the 21st century.

PMID- 15152051
TI  - A seed for Alzheimer amyloid in the brain.
AB  - A fundamental question about the early pathogenesis of Alzheimer's disease (AD)
      concerns how toxic aggregates of amyloid beta protein (Abeta) are formed from its
      nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound
      Abeta (GAbeta) is involved in the process. We now examined this possibility using
      a novel monoclonal antibody raised against GAbeta purified from an AD brain.
      Here, we report that GAbeta has a conformation distinct from that of soluble
      Abeta and initiates Abeta aggregation by acting as a seed. Furthermore, GAbeta
      generation in the brain was validated by both immunohistochemical and
      immunoprecipitation studies. These results imply a mechanism underlying the onset
      of AD and suggest that an endogenous seed can be a target of therapeutic
      strategy.

PMID- 15152054
TI  - What effect does measuring children under anesthesia have on the blood
      oxygenation level-dependent signal? A functional magnetic resonance imaging study
      of visual cortex.
AB  - We performed functional magnetic resonance measurements involving visual stimuli
      on 10 children. Half of the children were measured awake, the other half were
      measured under light Sevoflurane anesthesia corresponding to 0.5 mean alveolar
      concentration. Each child was presented with a flashed and a reversing
      checkerboard, which previous investigations have shown to induce identical
      increases in cerebral blood flow. The latter stimulus activated double the number
      of neurons as the former so that cerebral metabolic rate of oxygen consumption
      (CMRO(2)) was doubled, leading to an effective rise of the oxygen extraction
      fraction. We measured the extent of activation by counting the number of
      activated pixels and assessed the change in CMRO(2) by measuring the change in
      the local deoxyhemoglobin (HbR) concentration, using change in spin relaxivity.
      In both groups of children, the extent of activation was larger for the flashed
      than the reversing checkerboard, although the absolute number of activated voxels
      was smaller for the children who were measured under anesthesia. The HbR
      concentration was significantly higher during the presentation of the reversing
      compared with the flashed checkerboard. The relative change in the HbR
      concentration to the flashed and reversing checkerboard was the same in the
      children who were measured under anesthesia as in the children who were measured
      awake. We conclude that light levels of anesthesia may reduce the extent of
      activation but does not unduly influence either CMRO(2) or cerebral blood flow,
      thus preserving the blood oxygenation level-dependent signal amplitude.

PMID- 15152055
TI  - Biomedical research--an integral component of national security.

PMID- 15152056
TI  - Buying biosafety--is the price right?

PMID- 15152057
TI  - Pediatric antecedents of adult cardiovascular disease--awareness and
      intervention.

PMID- 15152058
TI  - Evidence-based use of cardiac procedures and devices.

PMID- 15152059
TI  - Cardiac-resynchronization therapy with or without an implantable defibrillator in
      advanced chronic heart failure.
AB  - BACKGROUND: We tested the hypothesis that prophylactic cardiac-resynchronization
      therapy in the form of biventricular stimulation with a pacemaker with or without
      a defibrillator would reduce the risk of death and hospitalization among patients
      with advanced chronic heart failure and intraventricular conduction delays.
      METHODS: A total of 1520 patients who had advanced heart failure (New York Heart
      Association class III or IV) due to ischemic or nonischemic cardiomyopathies and
      a QRS interval of at least 120 msec were randomly assigned in a 1:2:2 ratio to
      receive optimal pharmacologic therapy (diuretics, angiotensin-converting-enzyme
      inhibitors, beta-blockers, and spironolactone) alone or in combination with
      cardiac-resynchronization therapy with either a pacemaker or a pacemaker
      defibrillator. The primary composite end point was the time to death from or
      hospitalization for any cause. RESULTS: As compared with optimal pharmacologic
      therapy alone, cardiac-resynchronization therapy with a pacemaker decreased the
      risk of the primary end point (hazard ratio, 0.81; P=0.014), as did cardiac
      resynchronization therapy with a pacemaker-defibrillator (hazard ratio, 0.80;
      P=0.01). The risk of the combined end point of death from or hospitalization for
      heart failure was reduced by 34 percent in the pacemaker group (P<0.002) and by
      40 percent in the pacemaker-defibrillator group (P<0.001 for the comparison with
      the pharmacologic-therapy group). A pacemaker reduced the risk of the secondary
      end point of death from any cause by 24 percent (P=0.059), and a pacemaker
      defibrillator reduced the risk by 36 percent (P=0.003). CONCLUSIONS: In patients
      with advanced heart failure and a prolonged QRS interval, cardiac
      resynchronization therapy decreases the combined risk of death from any cause or
      first hospitalization and, when combined with an implantable defibrillator,
      significantly reduces mortality.

PMID- 15152060
TI  - Prophylactic defibrillator implantation in patients with nonischemic dilated
      cardiomyopathy.
AB  - BACKGROUND: Patients with nonischemic dilated cardiomyopathy are at substantial
      risk for sudden death from cardiac causes. However, the value of prophylactic
      implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden
      death in such patients is unknown. METHODS: We enrolled 458 patients with
      nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less
      than 36 percent, and premature ventricular complexes or nonsustained ventricular
      tachycardia. A total of 229 patients were randomly assigned to receive standard
      medical therapy, and 229 to receive standard medical therapy plus a single
      chamber ICD. RESULTS: Patients were followed for a mean (+/-SD) of 29.0+/-14.4
      months. The mean left ventricular ejection fraction was 21 percent. The vast
      majority of patients were treated with angiotensin-converting-enzyme (ACE)
      inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28
      in the ICD group, as compared with 40 in the standard-therapy group (hazard
      ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality
      rate at two years was 14.1 percent in the standard-therapy group (annual
      mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden
      deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard
      therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71;
      P=0.006). CONCLUSIONS: In patients with severe, nonischemic dilated
      cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the
      implantation of a cardioverter-defibrillator significantly reduced the risk of
      sudden death from arrhythmia and was associated with a nonsignificant reduction
      in the risk of death from any cause.

PMID- 15152061
TI  - Clinical practice. Plantar fasciitis.

PMID- 15152062
TI  - New drugs for rheumatoid arthritis.

PMID- 15152063
TI  - Images in clinical medicine. Acquired arteriovenous fistula.

PMID- 15152064
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 16-2004. A 76-year-old woman with numbness and pain in the feet
      and legs.

PMID- 15152065
TI  - Electromechanical associations.

PMID- 15152066
TI  - Why Medicare has not established criteria for coverage decisions.

PMID- 15152067
TI  - Medicare coverage for technological innovations--time for new criteria?

PMID- 15152068
TI  - Sex determination, differentiation, and identity.

PMID- 15152069
TI  - Vasopressin versus epinephrine for cardiopulmonary resuscitation.

PMID- 15152070
TI  - Folic acid and the prevention of neural-tube defects.

PMID- 15152071
TI  - Hepatitis A vaccine.

PMID- 15152072
TI  - Case 5-2004: a man with slurred speech and left hemiparesis.

PMID- 15152073
TI  - Management of overactive bladder.

PMID- 15152074
TI  - Priming with granulocyte colony-stimulating factor--relation to high-dose
      cytarabine in acute myeloid leukemia.

PMID- 15152075
TI  - Images in clinical medicine. Pericardial cyst.

PMID- 15152076
TI  - Integrated modeling of clinical and gene expression information for personalized
      prediction of disease outcomes.
AB  - We describe a comprehensive modeling approach to combining genomic and clinical
      data for personalized prediction in disease outcome studies. This integrated
      clinicogenomic modeling framework is based on statistical classification tree
      models that evaluate the contributions of multiple forms of data, both clinical
      and genomic, to define interactions of multiple risk factors that associate with
      the clinical outcome and derive predictions customized to the individual patient
      level. Gene expression data from DNA microarrays is represented by multiple,
      summary measures that we term metagenes; each metagene characterizes the dominant
      common expression pattern within a cluster of genes. A case study of primary
      breast cancer recurrence demonstrates that models using multiple metagenes
      combined with traditional clinical risk factors improve prediction accuracy at
      the individual patient level, delivering predictions more accurate than those
      made by using a single genomic predictor or clinical data alone. The analysis
      also highlights issues of communicating uncertainty in prediction and identifies
      combinations of clinical and genomic risk factors playing predictive roles.
      Implicated metagenes identify gene subsets with the potential to aid biological
      interpretation. This framework will extend to incorporate any form of data,
      including emerging forms of genomic data, and provides a platform for development
      of models for personalized prognosis.

PMID- 15152077
TI  - The statistical structure of natural light patterns determines perceived light
      intensity.
AB  - The same target luminance in different contexts can elicit markedly different
      perceptions of brightness, a fact that has long puzzled vision scientists. Here
      we test the proposal that the visual system encodes not luminance as such but
      rather the statistical relationship of a particular luminance to all possible
      luminance values experienced in natural contexts during evolution. This
      statistical conception of vision was validated by using a database of natural
      scenes in which we could determine the probability distribution functions of co
      occurring target and contextual luminance values. The distribution functions
      obtained in this way predict target brightness in response to a variety of
      challenging stimuli, thus explaining these otherwise puzzling percepts. That
      brightness is determined by the statistics of natural light patterns implies that
      the relevant neural circuitry is specifically organized to generate these
      probabilistic responses.

PMID- 15152079
TI  - Parkin and relatives: the RBR family of ubiquitin ligases.
AB  - Mutations in the parkin gene cause autosomal-recessive juvenile parkinsonism.
      Parkin encodes a ubiquitin-protein ligase characterized by having the RBR domain,
      composed of two RING fingers plus an IBR/DRIL domain. The RBR family is defined
      as the group of genes whose products contain an RBR domain. RBR family members
      exist in all eukaryotic species for which significant sequence data is available,
      including animals, plants, fungi, and several protists. The integration of
      comparative genomics with structural and functional data allows us to conclude
      that RBR proteins have multiple roles, not only in protein quality control
      mechanisms, but also as indirect regulators of transcription. A recently
      formulated hypothesis, based on a case of gene fusion, suggested that RBR
      proteins may be often part of cullin-containing ubiquitin ligase complexes.
      Recent data on Parkin protein agrees with that hypothesis. We discuss the
      involvement of RBR proteins in several neurodegenerative diseases and cancer.

PMID- 15152078
TI  - Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human
      retinal pigment epithelial cells from oxidative stress.
AB  - Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to
      retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes
      share the highest content of DHA of all cell membranes. This fatty acid is
      required for RPE functional integrity; however, it is not known whether specific
      mediators generated from DHA contribute to its biological significance. We used
      human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene
      [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore
      A-23187, by IL-1beta, or by supplying DHA. Under these conditions, there is a
      time-dependent release of endogenous free DHA followed by NPD1 formation,
      suggesting that phospholipase A(2) releases the mediator's precursor. Added NPD1
      potently counteracted H(2)O(2)/tumor necrosis factor alpha oxidative-stress
      triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic
      proteins Bcl-2 and Bcl-x(L) and decreased proapoptotic Bax and Bad expression.
      Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation.
      NPD1 also inhibited IL-1beta-stimulated expression of cyclooxygenase 2 promoter
      transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative
      stress-induced apoptosis, and we predict that it will similarly protect neurons.
      This lipid mediator therefore may indirectly contribute to photoreceptor cell
      survival as well. Because both RPE and photoreceptor cells die in retinal
      degenerations, our findings contribute to the understanding of retinal cell
      survival signaling and potentially to the development of new therapeutic
      strategies.

PMID- 15152080
TI  - Steroid sulfatase gene variation and DHEA responsiveness to resistance exercise
      in MERET.
AB  - Genetic influences and endurance exercise have been shown to alter circulating
      concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate,
      DHEAS. We hypothesized that acute resistance exercise (RE) and training (RET)
      would increase DHEA steroids, and the magnitude of the increase would be
      influenced by a steroid sulfatase (STS) gene variation. Fasting blood samples
      were collected before and after the first (S1) and last (S30) session of a 10-wk
      RET program in 62 men and 58 women [age: 21.0 yr (2.4)]. Acute RE increased both
      DHEA [+2.8 (0.4), S1; +1.6 ng/ml (0.4), S30; P < 0.001] and DHEAS [+154 (24), S1;
      +166 ng/ml (15), S30; P < 0.001] and decreased DHEAS:DHEA [-27 (8), S1; -15 (7),
      S30; P < 0.01]. RET reduced resting DHEAS (-122 ng/ml, P < 0.01) and decreased
      DHEA response to RE (-50%, P < 0.05). Subjects with an STS "G" allele (n = 36)
      had greater acute changes in DHEA [+4.4 (0.7) vs. +2.0 ng/ml (0.5), S1; +3.2
      (0.6) vs. +1.0 ng/ml (0.4), S30; P < 0.01] and DHEAS:DHEA [-37 (11) vs. 5 (7),
      S30, P < 0.05] than those subjects with only an "A" allele (n = 84). The observed
      increase in DHEA and DHEAS and decrease in DHEAS:DHEA suggest RE-induced STS
      activation which is influenced by the STS polymorphism.

PMID- 15152082
TI  - Solution structure of the hypothetical protein Mth677 from Methanobacterium
      thermoautotrophicum: a novel alpha+beta fold.
AB  - The structure of Mth677, a hypothetical protein from Methanobacterium
      thermoautotrophicum (Mth), has been determined by using heteronuclear nuclear
      magnetic resonance (NMR) methods on a double-labeled (15)N-(13)C sample. Mth677
      adopts a novel alpha+beta fold, consisting of two alpha-helices (one N terminal
      and one C terminal) packed on the same side of a central beta-hairpin. This
      structure is likely shared by its three orthologs, detected in three other
      Archaebacteria. There are no clear features in the sequences of these proteins or
      in the genome organization of Mth to make a reliable functional assignment to
      this protein. However, the structural similarity to Escherichia coli MinE, the
      protein which controls that division occurs at the midcell site, lends support to
      the proposal that Mth677 might be, in Mth, the counterpart of the topological
      specificity domain of MinE in E. coli.

PMID- 15152081
TI  - The ankyrin repeat as molecular architecture for protein recognition.
AB  - The ankyrin repeat is one of the most frequently observed amino acid motifs in
      protein databases. This protein-protein interaction module is involved in a
      diverse set of cellular functions, and consequently, defects in ankyrin repeat
      proteins have been found in a number of human diseases. Recent biophysical,
      crystallographic, and NMR studies have been used to measure the stability and
      define the various topological features of this motif in an effort to understand
      the structural basis of ankyrin repeat-mediated protein-protein interactions.
      Characterization of the folding and assembly pathways suggests that ankyrin
      repeat domains generally undergo a two-state folding transition despite their
      modular structure. Also, the large number of available sequences has allowed the
      ankyrin repeat to be used as a template for consensus-based protein design. Such
      projects have been successful in revealing positions responsible for structure
      and function in the ankyrin repeat as well as creating a potential universal
      scaffold for molecular recognition.

PMID- 15152083
TI  - A novel and conserved pocket of human kappa-Fab fragments: design, synthesis, and
      verification of directed affinity ligands.
AB  - Antibodies of type IgG may be divided into two classes, called lambda or kappa,
      depending on the type of light chain. We have identified a conserved pocket
      between the two domains CH1 and CL of human IgG kappa-Fab, which is not present
      in the lambda type. This pocket was used as a target docking site with the
      purpose of exploring the possibilities of designing affinity ligands that could
      function as such even after immobilization to gel. The idea of the design arose
      mainly from the results of the saturated transfer difference (STD-NMR) screening
      of 46 compounds identified by means of virtual docking of 60 K diverse compounds
      from the Available Chemicals Directory (ACD). Surface plasmon resonance (SPR) was
      used as an alternative method to monitor binding in solution. A total of 24
      compounds belonging to a directed library were designed, synthesized, and
      screened in solution. They consist essentially of an amino acid condensed to a
      N,N'-methylated phenyl urea. STD-NMR results suggest that a small hydrophobic
      side chain in the condensed amino acid promotes binding, whereas a hydroxyl-group
      containing side chain implies absence of STD-NMR signals. Three compounds of the
      directed library were immobilized and evaluated as chromatographic probes. In one
      case, using D-Pro as the condensed amino acid, columns packed with ligand-coupled
      Sepharose (Amersham Biosciences) retained two different monoclonal samples of
      kappa-Fab fragments with different variable regions, whereas a sample of
      monoclonal lambda-Fab fragments was not retained under similar chromatographic
      conditions.

PMID- 15152084
TI  - Incorporation of the fluorescent amino acid 7-azatryptophan into the core domain
      1-47 of hirudin as a probe of hirudin folding and thrombin recognition.
AB  - 7-Azatryptophan (AW), a noncoded isostere of tryptophan (W), possesses
      interesting spectral properties. In particular, the presence of a nitrogen atom
      at position 7 in the indolyl nucleus of AW results in a red shift of the
      absorption maximum and fluorescence emission by 10 and 46 nm, respectively,
      compared to W. In the present work, we report the chemical synthesis and the
      conformational and functional characterization of an analog (denoted as Y3AW) of
      the N-terminal domain 1-47 of hirudin, a highly potent thrombin inhibitor, in
      which Tyr 3 has been replaced by AW. The results obtained were compared with
      those of the corresponding Y3W analog. We found that the replacement W --> AW
      reduces affinity for thrombin by 10-fold, likely because of the lower
      hydrophobicity of AW compared with that of W. Measurements of the resonance
      energy transfer effect, which was observed between Tyr13 and the amino acid at
      position 3 upon disulfide-coupled folding, demonstrate that AW behaves as a
      better energy acceptor than W for studying protein renaturation. The interaction
      of Y3AW with thrombin was studied by exciting the sample at 320 nm and recording
      the change in fluorescence of Y3AW on binding to the enzyme. Our results indicate
      that the fluorescence of AW of hirudin 1-47 in the Y3AW-thrombin complex is
      strongly quenched, possibly because of the presence of two structural water
      molecules at the hirudin-thrombin interface that can promote the nonradiative
      decay of AW in the excited state. The data herein reported demonstrate that the
      incorporation of AW can be of broad applicability in the study of protein folding
      and protein-protein interaction.

PMID- 15152085
TI  - High resolution crystallographic studies of alpha-hemolysin-phospholipid
      complexes define heptamer-lipid head group interactions: implication for
      understanding protein-lipid interactions.
AB  - The alpha-hemolysin is an archetypal pore-forming protein that is secreted from
      Staphylococcus aureus as a water-soluble monomer. When the monomer binds to the
      membrane of a susceptible cell, the membrane-bound molecules assemble into the
      lytic heptamer. Although a bilayer or a bilayer-like environment are essential to
      toxin assembly, there is no high resolution information on toxin-phospholipid
      complexes. We have determined the structures of detergent-solubilized alpha
      hemolysin heptamer bound to glycerophosphocholine or dipropanoyl
      glycerophosphocholine at 1.75-1.80 A resolution and 110 K. The phosphocholine
      head group binds to each subunit in a crevice between the rim and the stem
      domains. The quaternary ammonium group interacts primarily with aromatic
      residues, whereas the phosphodiester moiety interacts with a conserved arginine
      residue. These structures provide a molecular basis for understanding why alpha
      hemolysin preferentially assembles on membranes comprised of phosphocholine
      lipids.

PMID- 15152086
TI  - The dimerization domain of the HIV-1 capsid protein binds a capsid protein
      derived peptide: a biophysical characterization.
AB  - The type 1 HIV presents a conical capsid formed by approximately 1500 units of
      the capsid protein, CA. Homodimerization of CA via its C-terminal domain, CA-C,
      constitutes a key step in virion assembly. CA-C dimerization is largely mediated
      by reciprocal interactions between residues of its second alpha-helix. Here, we
      show that an N-terminal-acetylated and C-terminal-amidated peptide, CAC1,
      comprising the sequence of the CA-C dimerization helix plus three flanking
      residues at each side, is able to form a complex with the entire CA-C domain.
      Thermal denaturation measurements followed by circular dichroism (CD), NMR, and
      size-exclusion chromatography provided evidence of the interaction between CAC1
      and CA-C. The apparent dissociation constant of the heterocomplex formed by CA-C
      and CAC1 was determined by several biophysical techniques, namely, fluorescence
      (using an anthraniloyl-labeled peptide), affinity chromatography, and isothermal
      titration calorimetry. The three techniques yielded similar values for the
      apparent dissociation constant, in the order of 50 microM. This apparent
      dissociation constant was only five times higher than was the dissociation
      constant of both CA-C and the intact capsid protein homodimers (10 microM).

PMID- 15152087
TI  - Theoretical study of interaction of winter flounder antifreeze protein with ice.
AB  - Antifreeze proteins (AFPs) are synthesized by various organisms to enable their
      cells to survive subzero environment. These proteins bind to small ice crystals
      and inhibit their growth, which if left uncontrolled would be fatal to cells. The
      crystal structures of a number of AFPs have been determined; however,
      crystallographic analysis of AFP-ice complex is nearly impossible. Molecular
      modeling studies of AFPs' interaction with ice surface is therefore invaluable.
      Early models of AFP-ice interaction suggested H-bond as the primary driving force
      behind such interaction. Recent experimental evidence, however, suggested that
      hydrophobic interactions could be the main contributor to AFP-ice association.
      All computational studies published to date were carried out to verify the H-bond
      model, and no works attempting to verify the hydrophobic interaction model have
      been published. In this work, we Monte Carlo-minimized complexes of several AFPs
      with ice taking into account nonbonded interactions, H-bonds, and the hydration
      potential for proteins. Parameters of the hydration potential for ice were
      developed with the assumption that the free energy of the water-ice association
      should be close to zero at equilibrium melting temperature. Our calculations
      demonstrate that desolvation of hydrophobic groups in the AFPs upon their binding
      to the grooves at the ice surface is indeed the major stabilizing contributor to
      the free energy of AFP-ice binding. This study is consistent with available
      structural and mutation data on AFPs. In particular, it explains the paradoxical
      finding that substitution of Thr residues with Val does not affect the potency of
      winter flounder AFP whereas substitution with Ser abolished its antifreeze
      activity.

PMID- 15152088
TI  - The ternary complex of Pseudomonas aeruginosa alcohol dehydrogenase with NADH and
      ethylene glycol.
AB  - Pseudomonas aeruginosa alcohol dehydrogenase (PaADH; ADH, EC 1.1.1.1) catalyzes
      the reversible oxidation of primary and secondary alcohols to the corresponding
      aldehydes and ketones, using NAD as coenzyme. We crystallized the ternary complex
      of PaADH with its coenzyme and a substrate molecule and determined its structure
      at a resolution of 2.3 A, using the molecular replacement method. The PaADH
      tetramer comprises four identical chains of 342 amino acid residues each and
      obeys ~222-point symmetry. The PaADH monomer is structurally similar to alcohol
      dehydrogenase monomers from vertebrates, archaea, and bacteria. The stabilization
      of the ternary complex of PaADH, the coenzyme, and the poor substrate ethylene
      glycol (k(cat) = 4.5 sec(-1); Km > 200 mM) was due to the blocked exit of the
      coenzyme in the crystalline state, combined with a high (2.5 M) concentration of
      the substrate. The structure of the ternary complex presents the precise geometry
      of the Zn coordination complex, the proton-shuttling system, and the hydride
      transfer path. The ternary complex structure also suggests that the low
      efficiency of ethylene glycol as a substrate results from the presence of a
      second hydroxyl group in this molecule.

PMID- 15152089
TI  - The structure of Ski8p, a protein regulating mRNA degradation: Implications for
      WD protein structure.
AB  - Ski8p is a 44-kD protein that primarily functions in the regulation of exosome
      mediated, 3'--> 5' degradation of damaged mRNA. It does so by forming a complex
      with two partner proteins, Ski2p and Ski3p, which complete a complex that is
      capable of recruiting and activating the exosome/Ski7p complex that functions in
      RNA degradation. Ski8p also functions in meiotic recombination in complex with
      Spo11 in yeast. It is one of the many hundreds of primarily eukaryotic proteins
      containing tandem copies of WD repeats (also known as WD40 or beta-transducin
      repeats), which are short ~40 amino acid motifs, often terminating in a Trp-Asp
      dipeptide. Genomic analyses have demonstrated that WD repeats are found in 1%-2%
      of proteins in a typical eukaryote, but are extremely rare in prokaryotes. Almost
      all structurally characterized WD-repeat proteins are composed of seven such
      repeats and fold into seven-bladed beta propellers. Ski8p was thought to contain
      five WD repeats on the basis of primary sequence analysis implying a five-bladed
      propeller. The 1.9 A crystal structure unexpectedly exhibits a seven-bladed
      propeller fold with seven structurally authentic WD repeats. Structure-based
      sequence alignments show additional sequence diversity in the two undetected
      repeats. This demonstrates that many WD repeats have not yet been identified in
      sequences and also raises the possibility that the seven-bladed propeller may be
      the predominant fold for this family of proteins.

PMID- 15152090
TI  - Modulation of the structural integrity of helix F in apomyoglobin by single amino
      acid replacements.
AB  - The conformational features of native and mutant forms of sperm-whale
      apomyoglobin (apoMb) at neutral pH were probed by limited proteolysis experiments
      utilizing up to eight proteases of different substrate specificities. It was
      shown that all proteases selectively cleave apoMb at the level of chain segment
      82-94 (HEAELKPLAQSHA), encompassing helix F in the X-ray structure of the holo
      form of the native protein; for example, thermolysin cleaves the Pro 88-Leu 89
      peptide bond. These results indicate that helix F is highly flexible or largely
      disrupted in apoMb. Because helix F contains the helix-breaking Pro 88 residue,
      we propose that helix F is kept in place in the native holo protein by a variety
      of helix-heme stabilizing interactions. To modulate the stability of helix F, the
      Pro88Ala and Pro88Gly mutants were prepared by site-directed mutagenesis, and
      their conformational properties investigated by both far-UV circular dichroism
      spectroscopy and limited proteolysis. The helix content of the Pro88Ala mutant
      was somewhat enhanced with respect to that of both native and Pro88Gly mutant, as
      expected from the fact that Ala is the strongest helix inducer among the 20 amino
      acid residues. The rate of limited proteolysis of the three apoMb variants by
      thermolysin and proteinase K was in the order native > Pro88Gly >> Pro88Ala, in
      agreement with the scale of helix propensity of Ala, Gly, and Pro. The possible
      role of the flexible/unfolded chain segment 82-94 for the function and fate of
      apoMb at the cellular level is discussed.

PMID- 15152091
TI  - Heterodimers of wild-type and subunit interface mutant enzymes of glutathione S
      transferase A1-1: interactive or independent active sites?
AB  - Heterodimers of rat glutathione S-transferase A1-1 were formed using one wild
      type subunit and one subunit with a mutation at the interface to evaluate whether
      the subunits are interactive or independent. Within the subunit interface, we are
      considering two regions of interactions: one region consists of a "hydrophobic
      ball and socket" with Phe 52 from one subunit as the ball and Phe 136 from the
      second subunit as one of the socket residues. The second region of interaction
      consists of Arg 69 and Glu 97 from both subunits. The heterodimers were formed
      after incubation in 1,6-hexanediol. Because one subunit in each pair had a His
      tag, the heterodimers were purified using a nickel-nitrilotriacetic acid column.
      The specific activities of the heterodimer were compared with those of the two
      homodimers to determine whether the less active, mutant subunit communicates with
      the other subunit. Two of the heterodimers, wild type/R69E-His and wild type/E97Q
      His, displayed specific activities much lower than that expected for independent
      active sites; in these cases, there are new close repulsive interactions and the
      low activity of one subunit is communicated to the neighboring subunit. In
      contrast, the other two heterodimers, wild type/R69Q-His and F136A/wild type-His,
      exhibited specific activities similar to those expected for independent active
      sites; in these heterodimers, the closest interaction is not repulsive or occurs
      over a much longer distance and the subunits act independently. We conclude that
      whether the subunits interact or are independent depends on the nature of the
      interactions at the subunit interface.

PMID- 15152092
TI  - Scoring profile-to-profile sequence alignments.
AB  - Sequence alignment profiles have been shown to be very powerful in creating
      accurate sequence alignments. Profiles are often used to search a sequence
      database with a local alignment algorithm. More accurate and longer alignments
      have been obtained with profile-to-profile comparison. There are several steps
      that must be performed in creating profile-profile alignments, and each involves
      choices in parameters and algorithms. These steps include (1) what sequences to
      include in a multiple alignment used to build each profile, (2) how to weight
      similar sequences in the multiple alignment and how to determine amino acid
      frequencies from the weighted alignment, (3) how to score a column from one
      profile aligned to a column of the other profile, (4) how to score gaps in the
      profile-profile alignment, and (5) how to include structural information. Large
      scale benchmarks consisting of pairs of homologous proteins with structurally
      determined sequence alignments are necessary for evaluating the efficacy of each
      scoring scheme. With such a benchmark, we have investigated the properties of
      profile-profile alignments and found that (1) with optimized gap penalties, most
      column-column scoring functions behave similarly to one another in alignment
      accuracy; (2) some functions, however, have much higher search sensitivity and
      specificity; (3) position-specific weighting schemes in determining amino acid
      counts in columns of multiple sequence alignments are better than sequence
      specific schemes; (4) removing positions in the profile with gaps in the query
      sequence results in better alignments; and (5) adding predicted and known
      secondary structure information improves alignments.

PMID- 15152093
TI  - Identification of the N-glycosylation sites on glutamate carboxypeptidase II
      necessary for proteolytic activity.
AB  - Glutamate carboxypeptidase II (GCPII) is a membrane peptidase expressed in the
      prostate, central and peripheral nervous system, kidney, small intestine, and
      tumor-associated neovasculature. The GCPII form expressed in the central nervous
      system, termed NAALADase, is responsible for the cleavage of N-acetyl-L-aspartyl
      L-glutamate (NAAG) yielding free glutamate in the synaptic cleft, and is
      implicated in various pathologic conditions associated with glutamate
      excitotoxicity. The prostate form of GCPII, termed prostate-specific membrane
      antigen (PSMA), is up-regulated in cancer and used as an effective prostate
      cancer marker. Little is known about the structure of this important
      pharmaceutical target. As a type II membrane protein, GCPII is heavily
      glycosylated. In this paper we show that N-glycosylation is vital for proper
      folding and subsequent secretion of human GCPII. Analysis of the predicted N
      glycosylation sites also provides evidence that these sites are critical for
      GCPII carboxypeptidase activity. We confirm that all predicted N-glycosylation
      sites are occupied by an oligosaccharide moiety and show that glycosylation at
      sites distant from the putative catalytic domain is critical for the NAAG
      hydrolyzing activity of GCPII calling the validity of previously described
      structural models of GCPII into question.

PMID- 15152094
TI  - Some fundamental aspects of building protein structures from fragment libraries.
AB  - We have investigated some of the basic principles that influence generation of
      protein structures using a fragment-based, random insertion method. We tested
      buildup methods and fragment library quality for accuracy in constructing a set
      of known structures. The parameters most influential in the construction
      procedure are bond and torsion angles with minor inaccuracies in bond angles
      alone causing >6 A CalphaRMSD for a 150-residue protein. Idealization to a
      standard set of values corrects this problem, but changes the torsion angles and
      does not work for every structure. Alternatively, we found using Cartesian
      coordinates instead of torsion angles did not reduce performance and can
      potentially increase speed and accuracy. Under conditions simulating ab initio
      structure prediction, fragment library quality can be suboptimal and still
      produce near-native structures. Using various clustering criteria, we created a
      number of libraries and used them to predict a set of native structures based on
      nonnative fragments. Local CalphaRMSD fit of fragments, library size, and
      takeoff/landing angle criteria weakly influence the accuracy of the models. Based
      on a fragment's minimal perturbation upon insertion into a known structure, a
      seminative fragment library was created that produced more accurate structures
      with fragments that were less similar to native fragments than the other sets.
      These results suggest that fragments need only contain native-like subsections,
      which when correctly overlapped, can recreate a native-like model. For fragment
      based, random insertion methods used in protein structure prediction and design,
      our findings help to define the parameters this method needs to generate near
      native structures.

PMID- 15152101
TI  - Anxious aging.

PMID- 15152095
TI  - New enzymes from environmental cassette arrays: functional attributes of a
      phosphotransferase and an RNA-methyltransferase.
AB  - By targeting gene cassettes by polymerase chain reaction (PCR) directly from
      environmentally derived DNA, we are able to amplify entire open reading frames
      (ORFs) independently of prior sequence knowledge. Approximately 10% of the mobile
      genes recovered by these means can be attributed to known protein families. Here
      we describe the characterization of two ORFs which show moderate homology to
      known proteins: (1) an aminoglycoside phosphotransferase displaying 25% sequence
      identity with APH(7") from Streptomyces hygroscopicus, and (2) an RNA
      methyltransferase sharing 25%-28% identity with a group of recently defined
      bacterial RNA methyltransferases distinct from the SpoU enzyme family. Our novel
      genes were expressed as recombinant products and assayed for appropriate enzyme
      activity. The aminoglycoside phosphotransferase displayed ATPase activity,
      consistent with the presence of characteristic Mg(2+)-binding residues. Unlike
      related APH(4) or APH(7") enzymes, however, this activity was not enhanced by
      hygromycin B or kanamycin, suggesting the normal substrate to be a different
      aminoglycoside. The RNA methyltransferase contains sequence motifs of the RNA
      methyltransferase superfamily, and our recombinant version showed
      methyltransferase activity with RNA. Our data confirm that gene cassettes present
      in the environment encode folded enzymes with novel sequence variation and
      demonstrable catalytic activity. Our PCR approach (cassette PCR) may be used to
      identify a diverse range of ORFs from any environmental sample, as well as to
      directly access the gene pool found in mobile gene cassettes commonly associated
      with integrons. This gene pool can be accessed from both cultured and uncultured
      microbial samples as a source of new enzymes and proteins.

PMID- 15152096
TI  - Replacement of proline with valine does not remove an apparent proline
      isomerization-dependent folding event in CRABP I.
AB  - Site-directed mutagenesis has frequently been used to replace proline with other
      amino acids in order to determine if proline isomerization is responsible for a
      slow phase during refolding. Replacement of Pro 85 with alanine in cellular
      retinoic acid binding protein I (CRABP-I) abolished the slowest refolding phase,
      suggesting that this phase is due to proline isomerization in the unfolded state.
      To further test this assumption, we mutated Pro 85 to valine, which is the
      conservative replacement in the two most closely related proteins in the family
      (cellular retinoic acid binding protein II and cellular retinol binding protein
      I). The mutant protein was about 1 kcal/mole more stable than wild type. Retinoic
      acid bound equally well to wild type and P85V-CRABP I, confirming the functional
      integrity of this mutation. The refolding and unfolding kinetics of the wild-type
      and mutant proteins were characterized by stopped flow fluorescence and circular
      dichroism. The mutant P85V protein refolded with three kinetic transitions, the
      same number as wild-type protein. This result conflicts with the P85A mutant,
      which lost the slowest refolding rate. The P85V mutation also lacked a kinetic
      unfolding intermediate found for wild-type protein. These data suggest that
      proline isomerization may not be responsible for the slowest folding phase of
      CRABP I. As such, the loss of a slow refolding phase upon mutation of a proline
      residue may not be diagnostic for proline isomerization effects on protein
      folding.

PMID- 15152097
TI  - Inhibition of the class II HMG-CoA reductase of Pseudomonas mevalonii.
AB  - There are two structural classes of HMG-CoA reductase, the third enzyme of the
      mevalonate pathway of isopentenyl diphosphate biosynthesis-the Class I enzymes of
      eukaryotes and the Class II enzymes of certain eubacteria. Structural
      requirements for ligand binding to the Class II HMG-CoA reductase of Pseudomonas
      mevalonii were investigated. For conversion of mevalonate to HMG-CoA the -CH(3), 
      OH, and -CH(2)COO(-) groups on carbon 3 of mevalonate were essential for ligand
      recognition. The statin drug Lovastatin inhibited both the conversion of HMG-CoA
      to mevalonate and the reverse of this reaction. Inhibition was competitive with
      respect to HMG-CoA or mevalonate and noncompetitive with respect to NADH or
      NAD(+). K(i) values were millimolar. The over 10(4)-fold difference in statin
      K(i) values that distinguishes the two classes of HMG-CoA reductase may result
      from differences in the specific contacts between the statin and residues present
      in the Class I enzymes but lacking in a Class II HMG-CoA reductase.

PMID- 15152102
TI  - Shining a light on long life.

PMID- 15152103
TI  - Early life predictors of old-age life expectancy.
AB  - The laboratory of Richard Miller and numerous heroic collaborators are in the
      process of testing a variety of life span predictors on more than 1000 mice. In
      their most recent publication, Harper et al. show that early-adulthood measures
      of T cell subsets, body weight, and thyroxine can be effectively combined to
      provide a highly significant predictor of life expectancy. Each measure appears
      to be an index of largely separate parameters that affect the course of aging.
      This article summarizes the results, discusses implications, mentions caveats,
      and suggests future studies.

PMID- 15152104
TI  - Hereditary haemochromatosis.
AB  - Hereditary haemochromatosis is a very common genetic defect in the Caucasian
      population, with an autosomal recessive inheritance. It is characterized by
      inappropriately increased iron absorption from the duodenum and upper intestine,
      with consequent deposition in various parenchymal organs, notably the liver,
      pancreas, joints, heart, pituitary gland and skin, with resultant end-organ
      damage. Clinical features may be non-specific and include lethargy and malaise,
      or reflect target organ damage and present with abnormal liver tests, cirrhosis,
      diabetes mellitus, arthropathy, cardiomyopathy, skin pigmentation and gonadal
      failure. Early recognition and treatment (phlebotomy) is essential to prevent
      irreversible complications such as cirrhosis and hepatocellular carcinoma. The
      history of this condition dates as far back as 1865, but in the last decade great
      advances have been made. We discuss the genetics, pathophysiology, clinical
      features, diagnosis and management of a condition that could easily present to a
      generalist, and is an important diagnosis not to miss.

PMID- 15152105
TI  - Herpes simplex encephalitis: an audit of the use of laboratory diagnostic tests.
AB  - BACKGROUND: The combination of both PCR and intrathecal antibody studies is
      recommended to confirm or refute the diagnosis of herpes simplex encephalitis
      (HSE). AIM: To investigate the pattern of use of laboratory tests in the
      diagnosis of suspected cases of HSE, and to determine the final diagnosis in
      cases proven not to be HSE. DESIGN: Structured audit. METHODS: We reviewed the
      case-notes of all patients who, over a five-year time period, presented with
      suspected encephalitis; and/or were prescribed aciclovir. Clinical and laboratory
      criteria were used to categorize the likelihood of HSE. RESULTS: We identified
      222 patients: 10 (5%) had definite HSE, 24 (10%) possible HSE, and 144 (65%) a
      definite alternative diagnosis. In 44 (20%), no final diagnosis was made, but the
      diagnosis of HSE was excluded. PCR was performed in 68 (31%), intrathecal
      antibody studies in 24 (11%), and brain biopsy in 17 (8%). A wide range of
      diseases mimicked HSE, but most common were inflammatory diseases and other
      infections of the central nervous system. DISCUSSION: Laboratory tests,
      particularly intrathecal antibody assays, are under-used in the diagnosis of HSE.
      Although early empirical treatment of suspected HSE is essential, confirmation or
      exclusion of the diagnosis is equally important to avoid overlooking alternative
      diagnoses. Identification of the aetiology of encephalitis is of particular
      importance, given the current concerns of emerging infections and bioterrorism.

PMID- 15152106
TI  - Knowledge of chronic hepatitis C among East London primary care physicians
      following the Department of Health's educational campaign.
AB  - BACKGROUND: In August 2002, the Department of Health (DH) wrote to all general
      practitioners (GPs) in England about hepatitis C, enclosing an educational
      booklet. AIM: To assess hepatitis C knowledge among East London GPs in June 2003.
      DESIGN: Postal questionnaire and face-to-face interviews. METHODS: A
      questionnaire was mailed to 250 (South-East) and 600 (North-East) London GPs,
      with reminders where needed. We randomly selected 10 GPs for face-to-face
      standardized interviews. RESULTS: Overall questionnaire response was 56% (South
      East) and 57% (North-East), with little difference between the groups. Some 86%
      knew that hepatitis C was common in people who inject drugs, and that its
      prevalence was higher than HIV. However, 14% believed that antibodies to the
      virus indicated that the patient no longer had active disease. Some 49% thought
      that materno-fetal transmission was common, and 50% believed that blood
      transfusion in the 1990s carried a high risk of infection. Only 23% knew that 20%
      of patients develop cirrhosis after 20 years, and only 58% were aware that
      therapy was effective in > 50% of cases. Responses among the interviewed GPs were
      similar. DISCUSSION: Knowledge of hepatitis C among GPs remains poor. Every GP
      surveyed wished to be better informed. We hope the DH will produce and audit
      further educational campaigns.

PMID- 15152107
TI  - Inappropriate requests for serum anti-epileptic drug levels in hospital practice.
AB  - BACKGROUND: Serum anti-epileptic drug (AED) levels are indicated to assess AED
      adherence or toxicity, and are applicable to only a few AEDs. Expert consensus
      views on the clinical role of serum AED levels are summarized in the evidence
      based guidelines published by the Scottish Intercollegiate Guidelines Network.
      AIM: To examine local compliance with these guidelines. DESIGN: Retrospective
      case-note audit. METHODS: We included all serum AED level measurements requested
      from our hospital over two months. Our audit standards were first, that serum AED
      levels should be requested only for suspicion of poor AED adherence or toxicity
      ('indication-compliant'), and secondly, for 'full compliance', that 'indication
      compliant' requests should be made only for AEDs with established dose-response
      and dose-toxicity relationships (phenytoin, carbamazepine, phenobarbitone).
      RESULTS: There were 114 measurements in 102 patients. Serum AED level requests
      were for phenytoin (n = 50), valproate (n = 27), carbamazepine (n = 22),
      lamotrigine (n = 8), phenobarbitone (n = 7), and were made by physicians (n =
      46), paediatricians (n = 30), neurologists (n = 15), neurosurgeons (n = 14),
      psychiatrists (n = 7), and intensivists (n = 2). AED toxicity was queried in 29
      requests (25%), and adherence in 10 (9%); thus 34% of requests were 'indication
      compliant'. However, 16 of these were for valproate or lamotrigine; thus only 23
      requests (20%) were 'fully compliant'. Clinical management changed in only 17 of
      the 47 patients whose levels fell outside target ranges, and only two of these
      followed indication-compliant AED measurement. DISCUSSION: The audit identified a
      failure locally to comply with standard evidence-based guidelines. If, as is
      likely, this reflects practice elsewhere in the UK, there are potentially major
      clinical management and resource implications.

PMID- 15152108
TI  - Effect of exercise versus relaxation on haemoglobin A1C in Black females with
      type 2 diabetes mellitus.
AB  - BACKGROUND: Evidence suggests that populations in Africa develop Type 2 diabetes
      mellitus (DM) at an increasing rate as they reject their traditional lifestyles.
      Diabetes is the tenth most common cause for total life years lost in females in
      South Africa. Physical activity is under-used in the management of type 2 DM in
      South Africa. AIM: To investigate the efficacy of an exercise intervention
      programme compared to relaxation exercises to decrease HbA1c over a period of 12
      weeks, in type 2 DM female subjects. DESIGN: Single blind, double-intervention
      randomized trial. METHODS: Clinical measurements were done before and after the
      12-week exercise and relaxation interventions. The interventions consisted of
      education and aerobic exercise for the exercise group, and education and
      relaxation for the second group. RESULTS: Adjusted baseline HbA1c change from
      baseline in the exercise group after 12 weeks was -0.39% (95%CI -0.80 to 0.02)
      and in the relaxation group -0.97% (95%CI -1.38 to 0.55) (p = 0.052). The results
      for the BMI were -0.07% kg/m2 (95%CI -0.2 to 0.14) in the exercise group versus 
      0.23 kg/m2 (95%CI -0.44 to 0.02) in the relaxation group (p = 0.28). The
      difference from baseline in distances covered following the 6 min walk test was
      statistically significantly greater (p < 0.01) in the exercise group: 46.76 m
      (95%CI 36.20-57.32) vs the relaxation group 22.7 m (95%CI 12.07-33.33).
      DISCUSSION: The exercise intervention failed to reduce the HbA1c to a greater
      extent than in the relaxation control group. Both groups improved significantly
      from baseline, probably due to the study effect.

PMID- 15152109
TI  - Restrictive use of immunosuppressive treatment in patients with idiopathic
      membranous nephropathy: high renal survival in a large patient cohort.
AB  - BACKGROUND: Immunosuppressive treatment initiated at an early stage in patients
      with idiopathic membranous nephropathy (iMN) improves renal survival. Treatment
      should ideally be restricted to high-risk patients. AIM: To evaluate the efficacy
      of a restrictive immunosuppressive treatment strategy for patients with iMN.
      DESIGN: Prospective cohort study evaluating a predefined treatment protocol.
      METHODS: From 1988, we adopted a restrictive treatment strategy:
      immunosuppressive treatment, mainly consisting of cyclophosphamide and steroids,
      was advised only in patients with renal insufficiency or severe intolerable
      nephrotic syndrome. We evaluated this strategy in a large patient cohort. To
      exclude any bias, we included all adult patients with iMN biopsied in the study
      period with a serum creatinine (Scr) < 135 micromol/l, a proteinuria > or = 3.0
      g/day and/or a serum albumin (Salb) < or = 30 g/l at the time of biopsy. Analysis
      was according to the intention-to-treat principle. RESULTS: We studied 69
      patients. At the time of biopsy, mean age was 51 years, Scr 90 micromol/l, Salb
      23 g/l and proteinuria 6.7 g/day. Average follow-up was 5.5 years. Thus far 33
      (48%) patients have received immunosuppressive therapy, mainly because of renal
      insufficiency (n = 24). Status at the end of follow-up was: complete remission n
      = 22 (32%), partial remission n = 24 (35%), nephrotic syndrome n = 15 (22%),
      persistent proteinuria n = 1 (1.4%), ESRD n = 6 (8.7%), death n = 1 (1.4%; due to
      bladder carcinoma after cyclophosphamide therapy). Patient survival was 100% at 5
      and 7 years. Renal survival was 94% at 5 years and 88% at 7 years. DISCUSSION: In
      patients with iMN, a restrictive treatment policy assures a favourable prognosis,
      while preventing exposure to immunosuppressive therapy in >50% of the patients.

PMID- 15152110
TI  - Thrombolysis in pulmonary embolism: are we under-using it?

PMID- 15152111
TI  - An unusual cause for ketoacidosis.
AB  - A 22-year-old male developed a severe degree of metabolic acidosis (plasma pH
      7.20, bicarbonate 8 mmol/l), with a large increase in the plasma anion gap (26
      mEq/l). Ketoacidosis was suspected because of the odour of acetone on his breath
      and a positive qualitative test for acetone in plasma (to a 1:4 dilution). Later,
      his plasma beta-hydroxybutyrate concentration was found to be 4.5 mmol/l. After
      receiving an infusion of 1 l of half-isotonic saline and 1 l of 5% dextrose in
      water over 24 h, as well as curtailing his large oral intake of sweetened
      beverages, all blood tests became normal. Diabetic ketoacidosis, alcoholic
      ketoacidosis, starvation ketosis and hypoglycaemic ketoacidosis were all ruled
      out, and his toxin screen was negative for salicylates. Finding another possible
      cause for ketoacidosis became the focus of this case.

PMID- 15152112
TI  - Pancreatic insufficiency and weight loss in older patients.

PMID- 15152113
TI  - Cost-effectiveness of cognitive behaviour therapy for patients with chronic
      fatigue syndrome.

PMID- 15152114
TI  - Cost-effectiveness of cognitive behaviour therapy for patients with chronic
      fatigue syndrome.

PMID- 15152115
TI  - How does X mark the spot?

PMID- 15152116
TI  - The itch.

PMID- 15152118
TI  - Left main coronary artery dissection detected by intravascular ultrasound
      following angiographically successful percutaneous coronary intervention.

PMID- 15152120
TI  - A case of renal artery brachytherapy for in-stent restenosis: four-year follow
      up.
AB  - Renal artery stent implantation is associated with high rates of restenosis,
      particularly in vessels less than 4.5 mm in diameter. We describe 4-year follow
      up results in the first patient to receive renal artery brachytherapy for this
      indication. A 68-year-old man who presented with flash pulmonary edema,
      hypertension and renal impairment was found to have severe bilateral renal artery
      stenosis and was treated with bilateral stent implantation. Following clinical
      deterioration due to severe in-stent restenosis, he underwent repeat angioplasty
      followed by intra-stent brachytherapy. To our knowledge, this is the first use of
      such therapy and hence the 4-year follow-up demonstrating excellent bilateral
      patency is the longest to date.

PMID- 15152119
TI  - Stenting of atherosclerotic stenoses in anomalously arising coronary arteries.
AB  - This description of five cases brings to 37 the total number of reported patients
      in whom atherosclerotic lesions of anomalously arising coronary arteries have
      been stented. One-half of these have been right coronary arteries arising from
      the left sinus of Valsalva, followed in frequency by branches of single coronary
      arteries arising from solitary aortic ostia and left circumflex arteries arising
      from the right sinus of Valsalva or from the proximal portion of the right
      coronary artery. Proper guide-catheter selection, essential for successful
      stenting, usually matches the guide's configuration to the sinus of Valsalva from
      which the anomalous artery originates rather than to the final distribution of
      the coronary artery.

PMID- 15152121
TI  - Unusual spontaneous repositioning of an amplatzer device embolized into the left
      atrium resulting in completed closure of atrial septal defect.
AB  - The authors described a rare case of spontaneous repositioning of an embolised
      Amplatzer occluder into the left atrium resulting in complete occlusion of a
      hemodynamically significant atrial septal defect, in the fossa ovalis, in a 70
      year-old man. Only a slight central residual shunting was present, as was shown
      by transesophageal Doppler echocardiography performed immediately after the
      procedure, with no apparent shunt at 30, 60 and 120 days after the intervention.

PMID- 15152122
TI  - Treatment of coronary aneurysm in acute myocardial infarction with AngioJet
      thrombectomy and JoStent coronary stent graft.
AB  - A 54-year-old male with a history of coronary artery disease with a percutaneous
      transluminal coronary angioplasty and stenting presented to the emergency with an
      acute myocardial infarction. The patient underwent angiography which showed in
      stent thrombosis of the right coronary artery along with 2 aneurysms proximal to
      the lesion. The right coronary artery was treated with AngioJet rheolytic
      thrombectomy and the JoStent coronary stent graft. To our knowledge, this is the
      first report of the use of the AngioJet rheolytic thrombectomy and the JoStent
      coronary stent graft in acute myocardial infarction.

PMID- 15152123
TI  - Effectiveness of the sirolimus-eluting stent in the treatment of saphenous vein
      graft disease.
AB  - The use of bare stents for the percutaneous intervention of saphenous vein bypass
      grafts (SVGs) is associated with a high subsequent rate of restenosis. To assess
      the impact of the sirolimus-eluting stent (SES), we studied 19 consecutive
      patients who underwent de novo SVG intervention treated solely with SES. Mean
      graft age was 10 years. Clinical presentation was an acute coronary syndrome in
      68%. In total, twenty-two de novo lesions were treated with 35 SESs (mean=1.6
      stents per lesion). Use of glycoprotein IIb/IIIa inhibitor therapy and distal
      embolization protection device were at operator discretion and were 42% and 32%,
      respectively. The rate of in-hospital major adverse cardiac events (MACE) was
      11%, related to 2 patients with a creatine kinase rise consistent with peri
      procedural acute myocardial infarction (AMI); a distal protection device was not
      utilized in either. Over a mean 12.5+/-2.6 month follow-up, one patient died from
      a non-cardiac cause, and there were no further AMIs. Target lesion
      revascularization was undertaken in 1 patient (5%); survival free of MACE was
      84%. In conclusion, utilizing SESs for percutaneous intervention of degenerate
      SVGs is associated with a low rate of target vessel revascularization. Increased
      utilization of distal protection devices might reduce the peri-procedural rate of
      AMI.

PMID- 15152124
TI  - Drug-eluting stents and saphenous vein graft intervention.

PMID- 15152126
TI  - New anticoagulation.

PMID- 15152125
TI  - The use of bivalirudin to prevent subacute thrombosis during drug-eluting stent
      implantation.
AB  - Subacute thrombosis is an infrequent but potentially life-threatening
      complication of percutaneous coronary intervention (PCI) that has received much
      attention in association with drug-eluting stent (DES) deployment. We performed a
      retrospective case record review of 186 patients receiving PCI with DES placement
      at our facility. Patients received either bivalirudin (n=115) or heparin (n=71)
      as the foundation anticoagulant, with additional antiplatelet therapy as
      warranted. Two subacute thrombosis complications occurred and are described in
      detail. There were no deaths, major bleeding episodes or other significant
      complications. We report our findings and conclude that the addition of a
      glycoprotein IIb/IIIa inhibitor does not eliminate the risk of subacute
      thrombosis and that bivalirudin appears to provide effective anticoagulation for
      patients undergoing PCI with placement of a DES.

PMID- 15152127
TI  - Use of FemoStop system for arterial puncture site closure after coronary
      angioplasty.
AB  - Different protocols exist concerning the method and timing of post-coronary
      angioplasty arterial puncture site closure. Easy handling and good effectiveness
      are well-documented for the Femostop femoral artery compression system; however,
      no hard data exist concerning the relationship between heparin anticoagulation
      level and femoral artery compression time (FSCT). Thus, we prospectively
      randomized 267 patients after elective percutaneous transluminal coronary
      angioplasty (PTCA) into two groups [group A (n=137) had early sheath removal 6 to
      8 hours after PTCA; group B (n=130) had late sheath removal 14 to 16 hours after
      PTCA] and analyzed the dependence of the FSCT on the heparin anticoagulation
      level (aPTT) and the incidence of vagal reactions and puncture site
      complications. FSCT was significantly longer in group A (69+/-27 minutes versus
      45+/-15 minutes; p<0.001) with high heparin anticoagulation level (aPTT, 88+/-46
      seconds) in comparison to group B with low heparinization (aPTT, 59+/-34
      seconds). Vagal reactions occurred more frequently in group A (15.3% versus
      10.0%; p<0.01) and the incidence of minor hemorrhage at the arterial puncture
      site was also increased (9.5% versus 3.1%; p<0.05). In the clinical setting of
      intensive heparin anticoagulation and early sheath removal after PTCA (<8 hours),
      the FemoStop system cannot be recommended due to prolonged femoral artery
      compression times.

PMID- 15152128
TI  - A meta-analysis of percutaneous vascular closure devices after diagnostic
      catheterization and percutaneous coronary intervention.
AB  - BACKGROUND: While each of the available femoral arterial sealing devices claims
      equivalent safety to manual compression following invasive cardiac procedures,
      these claims are based on small, underpowered studies. Our aim was to increase
      the ability to detect a clinically meaningful difference by performing a meta
      analysis. METHODS: We identified studies via Medline and manual searches and
      selected studies that were prospective, randomized clinical trials for inclusion.
      Pooling of data was performed by calculation of the Mantel-Haenszel odds ratio
      (OR) and the variance of the OR was estimated using the method of Robins,
      Greenland and Breslow. RESULTS: Sixteen studies enrolling 5,048 patients were
      included in the analysis. The pooled OR was 0.89 (95% confidence interval, 0.86
      0.91), indicating a significant decrease in risk by devices. Excluding hematomas
      from the endpoint resulted in a concordant result. Angio-Seal was associated with
      a significant reduction in risk (OR, 0.51) and Perclose had a neutral result (OR,
      1.0), whereas Vasoseal had an increased risk of complications (OR, 1.18).
      CONCLUSION: Overall, sealing devices may be associated with a reduction in risk
      of complications following invasive coronary procedures, but significant
      differences may exist among individual devices. These potential differences need
      to be explored in randomized, controlled clinical trials.

PMID- 15152130
TI  - Vascular closure device complications: the case is not closed yet.

PMID- 15152129
TI  - Impact of gender on femoral access complications secondary to application of a
      collagen-based vascular closure device.
AB  - BACKGROUND: Vascular complications at the femoral access site continue to be a
      significant problem after cardiac catheterization procedures. It was the aim of
      the present study to assess the impact of gender on the incidence of severe
      femoral access complications following the application of a collagen-based
      vascular closure device after transfemoral catheterization procedures. METHODS: A
      total of 1,294 consecutive patients (977 male, 317 female) underwent closure of
      femoral access sites with 8F collagen-based vascular closure devices (Angioseal)
      immediately after diagnostic or interventional coronary catheterization
      procedures, independently of the coagulation status. All patients were closely
      monitored for the occurrence of complications during the following 24 hours.
      RESULTS: Between male and female patients, there was no difference in the
      technical performance of the device with successful deployment being achieved in
      96.7% and 95.9%, respectively (p=0.60). Severe access complications were found to
      be significantly higher in female versus male patients (1.6% vs. 0.2%; Odds ratio
      7.7, 95% confidence interval 1.5-40.1; p=0.015), although similar accomplishment
      of an immediate hemostasis was seen in 92.8% and 92.4% of male and female
      patients (p=0.98). CONCLUSION: Women show a significantly increased risk of
      developing severe femoral access complications secondary to the application of a
      collagen-based vascular closure device, although the overall incidence of these
      complications is relatively low. We speculate that the increased risk in women
      may be related to smaller arterial dimensions, which could be evaluated by
      femoral angiography prior to deployment of a closure device.

PMID- 15152131
TI  - Clinical and angiographic outcomes after Tsunami coronary stent placement.
AB  - STUDY AIM: The aim of this study was to determine six months restenosis rate
      measured by off-line quantitative coronary angiography, and to assess the
      efficacy and safety of newly developed six cells Tsunami stent system for the
      treatment of symptomatic, de novo, native coronary artery lesions. STUDY DESIGN
      AND METHODS: Between January and August 2001, 100 patients with 120 lesions were
      included at four clinical sites in this prospective, non-randomized, single arm
      study. In 35% of the patients two or more stents were implanted, 15% of the
      lesions were stented with more than one stent and 46% of the lesions were in
      small vessels (<or= 2.75 mm). The Tsunami stent was available in 10, 15, 20 and
      30 mm, length, and 3, 3.5 and 4 mm diameter. Angiographic success rate for
      stented lesions was 100% (residual diameter stenosis <or= 30%) and procedural
      success rate was 98%. Mean reference vessel diameter by QCA was 2.83 +/- 0.52,
      and post-procedural minimal lumen diameter was 2.59+/-0.4. Six months
      angiographic follow-up was available for 81% of the patients and revealed an in
      stent restenosis rate of 13.8% for all lesions and 7.4% for single stented
      lesions. At 30 days 98% and at 6 months 88% of the patients remained free of
      major adverse cardiac events. CONCLUSION: Based on the clinical and angiographic
      results of the present study we can conclude that the Tsunami stent provides safe
      and effective percutaneous treatment of obstructive coronary artery disease.

PMID- 15152132
TI  - Methods for the economic and quality of life supplement to the cilostazol for
      RESTenosis (CREST) trial.
AB  - OBJECTIVE: To determine economic and quality of life outcomes for the Cilostazol
      for RESTenosis (CREST) trial, which is investigating the efficacy of cilostazol
      vs. placebo in preventing post-stent restenosis. DESIGN: CREST is a prospective,
      multicenter, randomized, placebo-controlled, double-blind trial. SETTING: 20
      clinical sites; the Emory Center for Outcomes Research (ECOR) will serve as the
      economic and data coordinating center. PATIENTS: 705 patients (>18 years) who
      have undergone successful, uncomplicated placement of an intracoronary stent in a
      native coronary artery. INTERVENTION: Cilostazol (100 mg twice daily) or placebo
      for 6 months. OUTCOME MEASURES:  COSTS: Primary endpoint, total direct medical
      costs at 6 months; secondary endpoints, initial hospital costs and follow-up
      costs. QOL: Health-related quality of life (QOL) will be assessed using the EQ-5D
      and the Seattle Angina Questionnaire at baseline and at 1, 3, and 6 months. Cost
      effectiveness analysis: Preliminary data show that cilostazol is clinically
      superior to placebo and if the mean cost for the cilostazol arm is higher than
      that for placebo, cost-effectiveness analysis will be determined for the cost per
      episode of restenosis prevented, the cost per episode of major clinical and
      angiographic endpoints averted, and the cost per quality-adjusted life-years
      gained.

PMID- 15152133
TI  - Potential for myocardial salvage utilizing direct intracoronary infusion of
      aqueous oxygen.

PMID- 15152134
TI  - Fracture of a coronary guidewire during graft thrombectomy with the X-sizer
      device.
AB  - We present the first case reported of fracture of a coronary guidewire during
      thrombectomy of a massive thrombus in a recently occluded coronary bypass graft
      with the recently developed atherectomy catheter X-Sizer. The thrombus was
      successfully aspirated without distal embolisation and the guidewire fragment was
      trapped in the graft after covering with a coronary stent. Possible reasons for
      this unusual complication of X-Sizer are discussed.

PMID- 15152135
TI  - Single coronary artery, with anomalous origin of the left anterior descending
      artery from the right coronary artery, and anomalous right superior septal
      artery.

PMID- 15152136
TI  - Intercoronary communication with unidirectional blood flow.
AB  - Intercoronary communication is a rare condition in which there is an open-ended
      circulation with bidirectional blood flow between two coronary arteries. This
      report highlights a case of an intercoronary connection between the right
      coronary and circumflex arteries with unidirectional flow. Selective injection of
      the right coronary artery showed retrograde filling only of the circumflex
      artery, but left coronary injection did not fill the right coronary artery.

PMID- 15152137
TI  - Combination antithrombotic therapy with antiplatelet agents and anticoagulants
      for patients with atherosclerotic heart disease.
AB  - We reviewed the efficacy and safety of combination antithrombotic therapy with
      aspirin plus warfarin versus aspirin alone in patients with atherosclerotic heart
      disease. We performed a comprehensive MEDLINE search of English-language reports
      published between 1966 and 2002 and search of references and relevant papers.
      Only clinical research studies on primary or secondary prevention of
      cardiovascular events in patients at high risk for coronary artery disease or
      patients experiencing unstable angina or myocardial infarction were included.
      Despite daily aspirin treatment, many patients break through aspirin treatment
      and experience cardiovascular events. Individuals at high risk for coronary
      disease or with established disease benefit from combination therapy with aspirin
      plus warfarin, if compliance with warfarin is greater than 70% and the target
      international normalized ratio (INR) of 2.0-2.5 is achieved. Combination therapy
      within these parameters leads to a 29-45% reduction in the risk of death,
      reinfarction and/or ischemic stroke. There is a significant increase in the rate
      of minor and a slight increase in the rate of major bleeding with combination
      therapy. Other potential indications for combination therapy include myocardial
      infarction associated with acute left ventricular aneurysm or significant left
      ventricular systolic dysfunction. In spite of reluctance to use oral
      anticoagulants, several large, randomized clinical trials support combination
      therapy with aspirin plus warfarin (INR, 2.0-2.5) in high-risk patients with
      atherosclerotic heart disease. Combination therapy increases the risk of minor
      and major bleeding, but not intracranial bleeding.

PMID- 15152138
TI  - Platelet aggregation according to body mass index in patients undergoing coronary
      stenting: should clopidogrel loading-dose be weight adjusted?
AB  - BACKGROUND: A 300 mg clopidogrel loading-dose (LD) is widely used as an adjunct
      antithrombotic treatment to reduce the risk of thrombotic events early after
      coronary stenting (CS). Antithrombotic drugs commonly used during percutaneous
      coronary interventions, such as heparin and platelet glycoprotein IIb/IIIa
      inhibitors, but not clopidogrel LD, are weight-adjusted, and few data are
      available on which is the most effective clopidogrel LD regimen. The aim of this
      study was to assess whether body mass index (BMI) influenced platelet response to
      clopidogrel LD in patients undergoing CS. METHODS: Adenosine diphosphate (ADP)
      induced platelet aggregation (PA) was assessed by light transmittance
      aggregometry in 48 patients on aspirin treatment undergoing CS receiving a 300 mg
      clopidogrel LD at intervention time. PA was assessed at baseline and up to 24
      hours after intervention. Patients were divided into 2 groups according to BMI:
      overweight (BMI greater than or equal to 25 kg/m2; 29 patients) and normal weight
      (BMI<25 kg/m2; 19 patients). PA was significantly higher in overweight than in
      normal weight patients at baseline (60.1+/-18.6%; versus 47.6+/-13.5%; p=0.01),
      at 24 hours (42.3+/-18.4% versus 38.5+/-18.3%; p=0.02) and during the overall
      study time (p=0.025). Percentage of inhibition of PA 24 hours following
      clopidogrel LD was suboptimal (<40%) in 59% and 26% of overweight and normal
      weight patients, respectively (p=0.04). An elevated BMI was the only independent
      predictor of suboptimal platelet response. CONCLUSION: These data suggest that
      overweight patients may need a higher loading-dose of clopidogrel and/or an
      adjunct antithrombotic treatment to adequately inhibit platelet aggregation early
      after CS.

PMID- 15152139
TI  - Clopidogrel dosing in overweight patients: does one size fit all?

PMID- 15152140
TI  - Excimer laser revascularization of saphenous vein grafts in acute myocardial
      infarction.
AB  - Patients who develop acute myocardial infarction due to occlusion in a saphenous
      vein graft (SVG) constitute a revascularization challenge. Excimer laser
      angioplasty may have a potential advantage in the treatment of SVGs, since its
      308 nanometer wavelength is avidly absorbed by both atherosclerotic plaque and
      thrombus. The data presented herein support the notion that excimer laser
      angioplasty is a technology that has a potential role in achieving adequate
      revascularization outcomes in this selected, high-risk patient population.

PMID- 15152141
TI  - Impact of intraaortic balloon counterpulsation on arterial blood flow in juvenile
      pigs with heart failure.
AB  - OBJECTIVES: To assess the impact of intraaortic balloon counterpulsation on
      coronary, renal and aortic blood flow in an animal heart failure model.
      BACKGROUND: Heart failure exacerbations are still often treated with inotropic
      medications despite a lack of evidence demonstrating any benefit with these
      drugs. Intraaortic balloon counterpulsation may be considered in certain cases a
      bridge to recovery. METHODS: Four juvenile pigs underwent pacemaker implantation
      to induce a rapid-pacing mediated dilated cardiomyopathy. After approximately 4
      weeks of rapid pacing, the mean ejection fraction was reduced to 28.8+/-9.5% with
      a mean systolic blood pressure of 64/44 mmHg. The pigs then underwent surgical
      placement of flow probes around the circumflex coronary artery, renal artery and
      infrarenal aorta. A Millar catheter was used to calculate Dp/Dt and a Swan-Ganz
      to calculate cardiac output. Data were recorded at baseline and after 10 minutes
      of balloon pumping. The pigs were euthanized post-procedure. RESULTS: Coronary
      blood flow was increased 9.7% by balloon counterpulsation from 38.3 +/- 12.0 to
      42.0+/-11.4 ml/s (p=NS). Renal blood flow was reduced 11.9% by counterpulsation
      from 130.0+/-88.6 ml/s to 114.5+/-76.6 ml/s (p=NS). Infrarenal aortic blood flow
      was not changed (mean of 900 ml/s with and without counterpulsation); blood
      pressure, cardiac output and Dp/Dt were not changed after 10 minutes of pumping.
      There was little impact observed by changing the position of the balloon closer
      to or farther away from the apex of the aortic arch. CONCLUSION: Intraaortic
      balloon counterpulsation did not significantly improve hemodynamics in the pig
      heart failure model. This may be attributed to the high compliance of the
      juvenile pig's aorta, thus attenuating the pressure wave generated by
      counterpulsation. A larger volume balloon would merit investigation for this
      application.

PMID- 15152142
TI  - Intraaortic balloon counterpulsation in juvenile pigs.

PMID- 15152143
TI  - Effect of completeness of revascularization on clinical outcome in patients with
      multivessel disease presenting with unstable angina who undergo percutaneous
      coronary intervention.
AB  - We evaluated the current short- and medium-term outcomes of complete
      revascularization, compared to culprit lesion percutaneous coronary intervention
      (PCI), in patients with multivessel coronary disease presenting with unstable
      angina. One hundred fifty-one patients with multivessel coronary disease
      presented to a tertiary cardiothoracic center with unstable angina/non-ST
      elevation myocardial infarction (UA/NSTEMI) between January 2000 and September
      2001. In group A (n=71), the intended strategy was complete revascularization by
      multivessel PCI. In group B (n=80), culprit lesion PCI was intended despite the
      presence of other lesions amenable to PCI (B1) or due to confounding anatomical
      factors (B2). Clinical variables and endpoints were collected from patient notes,
      a dedicated database and telephone follow-up, and included recurrent stable and
      unstable angina, need for repeat PCI or elective coronary artery bypass graft,
      incidence of non-fatal myocardial infarction (MI) and death. Baseline
      characteristics were similar in each group. Procedural success was achieved in
      over 95% of cases in both groups with high stent implantation rates (>96%). There
      was no observed difference in mortality or incidence of MI between the groups.
      Compared to group A, more patients in group B1 had residual angina [22.8% (13/57)
      versus 9.9% (7/71); p=0.041] and required further PCI [17.5% (10/57) versus 7.0%
      (5/71); p=0.045]. There was a non-significant trend toward fewer readmissions for
      UA and less long-term antianginal medication in group A [38.0% (27/71) versus
      52.6% (30/57); p=0.043]. Complete and culprit lesion revascularization by PCI are
      safe methods of treating patients with multivessel coronary disease presenting
      with UA/NSTEMI. Reductions in residual angina, repeat PCI and need for
      antianginal therapies suggest that complete revascularization should be the
      strategy of choice when possible.

PMID- 15152145
TI  - Embolization--a pathological mechanism in renal artery stenosis.

PMID- 15152144
TI  - Renal function and survival after renal artery stent revascularization may be
      influenced by embolic debris.
AB  - Four years of follow-up renal function and survival data were obtained on 544
      patients who underwent 714 successful renal artery stenosis (RAS) stent
      revascularizations. The mean serum creatinine (SCr) was unchanged at 4 years
      (1.6+/-1.0 mg/dl versus 1.6+/-0.9 mg/dl). The 2-year paired comparison analysis
      revealed no change in the reciprocal of the SCr (1/SCr), when compared with
      baseline or 1-year follow-up values. Simple linear regression analysis revealed
      flat post-procedure trend line slopes within all patient subsets, which implied
      renal functional stabilization. The 4-year mortality rate was 20%; variables
      directly affecting survival were presence of 1 or 2 kidneys, whether 1 or 2 renal
      arteries were stenotic [survival: unilateral 87%, bilateral 80%, and solitary
      kidney 60% (p<0.05)], as well as the degree of renal dysfunction [normal renal
      function patients had a significantly better (p<0.05) survival (88%) than those
      with moderate (60%) or severe dysfunction (47%)]. Surprisingly, medication
      controlled blood pressure (BP) patients fared worse than those with poorly
      controlled BP (56% versus 70%, respectively; p<0.05), with the worst outcomes in
      controlled BP patients with bilateral disease compared to poorly controlled BP
      patients (35% versus 69%, respectively; p<0.05). CONCLUSION: Renal function
      remained stable following stent revascularization for RAS, and survival was
      adversely affected by the variables of unilateral or bilateral RAS, presence of
      one/two kidneys, renal function impairment and medically controlled BP. These
      data underscored the premise that the malignant nephropathy associated with RAS
      was more likely to be segmental than uniform, and resulted from recurrent debris
      embolization from the obstructing lesion rather than persistent ischemia. Thus, a
      randomized stent revascularization trial utilizing an embolic protection device,
      coupled with an effort to collect retrospective preoperative SCr values, may be
      able to demonstrate post-stent functional stabilization, halting of progressive
      functional deterioration and, potentially, improvement in survival.

PMID- 15152146
TI  - Extensive thrombus of distal anastomosis of saphenous vein graft.

PMID- 15152147
TI  - Pseudo-candy wrapper: bifocal radial artery graft spasm following stent
      implantation.
AB  - We encountered a case of intractable radial artery graft spasm after stent
      implantation which was partially responsive to nominal nitroglycerin therapy. We
      report this case with intravascular ultrasound imaging at the radial artery spasm
      site.

PMID- 15152149
TI  - Choosing the right cardiovascular delivery model for your hospital: "for all of
      the right reasons".

PMID- 15152148
TI  - Percutaneous transseptal myocardial ablation with wire (PTSAW): a new technique.
AB  - Alcohol septal ablation has recently been described as a safe alternative to
      surgical myectomy for treatment of symptomatic patients with hypertrophic
      obstructive cardiomyopathy. We describe a case where percutaneous myectomy was
      performed by mechanically occluding the septal artery using thrombogenic floppy
      tips of used PTCA wires instead of alcohol, as the anatomy of the septal artery
      was not suitable for alcohol ablation.

PMID- 15152150
TI  - Right-sided pulsus alternans in prosthetic mitral valve thrombosis.

PMID- 15152151
TI  - Transcatheter embolization of recanalized coronary artery fistula with Nit-Occlud
      device.
AB  - Congenital coronary artery fistula is a rare anomaly with varying symptomatology
      that may be addressed with surgical or interventional closure. Recanalization
      after complete occlusion of a coronary artery fistula has only been reported
      after surgical but not after interventional closure. We present a case of
      coronary artery fistula recanalization after angiographically documented complete
      transcatheter occlusion with Gianturco coils. The fistula was successfully
      managed by transcatheter implantation of a Nit-Occlud system, originally designed
      for interventional closure of patent ductus arteriosus.

PMID- 15152152
TI  - PR-segment elevation in inferior leads: an atypical electrocardiographic sign of
      atrial infarction.

PMID- 15152153
TI  - Use of corticosteroids in the treatment of cholesterol crystal embolization after
      percutaneous transluminal coronary angioplasty and stent placement.
AB  - Cholesterol crystal embolization is a rare but recognized complication of cardiac
      catheterization. While management has traditionally been supportive only, we
      demonstrate the successful use of corticosteroids in treatment of a patient with
      cholesterol crystal embolization to the distal extremity.

PMID- 15152154
TI  - Vascular brachytherapy: a new approach to renal artery in-stent restenosis.
AB  - Renovascular hypertension is frequently the result of atherosclerosis and has
      been successfully treated with percutaneous angioplasty. Stenting of vessels has
      helped to significantly lower the rate of restenosis after angioplasty; however,
      neointimal hyperplasia frequently results in growth of tissue through the stent,
      causing in-stent restenosis. Similar problems are seen in coronary stenting, and
      vascular brachytherapy has been shown to effectively prevent repeat in-stent
      restenosis. While coronary and renal restenoses occur by a common physiologic
      mechanism, their anatomic differences have prevented widespread adaptation of
      vascular brachytherapy to renal in-stent restenoses. A number of recent reports
      have demonstrated efficacy of renal vascular brachytherapy, but thus far, no
      large-scale, randomized data is available. Herein is reviewed the subject of
      renal vascular brachytherapy and the studies that are presently used in its
      justification.

PMID- 15152155
TI  - Percutaneous coronary interventions in diabetic patients: is complete
      revascularization important?
AB  - BACKGROUND: The long-term prognosis of diabetic patients with multivessel
      coronary artery disease (CAD) treated by surgical or percutaneous coronary
      revascularization is significantly worse as compared to non-diabetics. Lower
      rates of complete revascularization may be one factor that influences the poor
      long-term outcome in the diabetic population. Our study assessed the impact of
      complete revascularization on the long-term prognosis in diabetic patients with
      CAD treated by percutaneous coronary intervention (PCI). The study included 658
      consecutive diabetic patients (mean age, 60.9+/-10.1 years) who underwent PCI.
      Multivessel disease was present in 352 patients (53.5%). Revascularization was
      complete in 94 (26.7%) and incomplete in 258 (73.3%) patients with multivessel
      disease. Reasons for incomplete revascularization included angioplasty of only
      the culprit lesion (43.4%); small vessel size (22.8%); moderate lesion, defined
      as diameter stenosis 50-69% (18.6%); chronic total occlusion of the non
      intervened vessel (6.6%); and others (8.5%). Overall survival rate at 5 years was
      87.4%. Patients who underwent complete revascularization had a 94.5% survival
      rate, compared to 83.0% for those with incomplete revascularization (p<0.001).
      Similarly, the rates of myocardial infarction-free survival were significantly
      higher in patients with complete versus incomplete revascularization (92.9%
      versus 79.9%, respectively). Incomplete revascularization was the most powerful
      independent predictor of mortality at follow-up (relative risk 95% confidence
      interval, 1.54-7.69; p=0.003). Our data suggest that complete myocardial
      revascularization may improve the long-term prognosis after PCI of diabetic
      patients with multivessel CAD.

PMID- 15152156
TI  - Percutaneous coronary revascularization in diabetic patients with multivessel
      coronary artery disease: importance and feasibility.

PMID- 15152157
TI  - Interaction between a perfluorocarbon emulsion and radiographic contrast media.
AB  - This study evaluated specially designed perfluorocarbon (PFC) emulsions as blood
      substitutes in case of induced ischemia of the left heart ventricle in healthy
      farm pigs. Two hundred ml of perfluorocarbon emulsion were infused while 200 ml
      of blood were simultaneously drawn. Radiographic contrast media were given to aid
      placement of balloon catheters in the left coronary artery. Histopathological
      analysis showed that right heart failure caused the deaths of both pigs.
      Particles (up to>3 micro) of foreign body materials obstructed capillaries of all
      organs analyzed (heart, lung, liver, kidneys and spleen). Laboratory
      investigation showed severe interference between the PFC emulsion and
      radiographic contrast media, resulting in the deterioration of the PFC emulsion.
      The strongest interference occurred when PFC emulsion and Accupaque interacted;
      particle size started at an initial 311 nm and went up to >3 micro within
      seconds. Great care must be taken when PFC emulsions are used in combination with
      x-ray contrast media. None of the described radiographic contrast media should be
      used within 48 hours prior to the use of this PFC emulsion. Also, the use of
      these contrast media should be avoided for a certain period of time after using
      PFC emulsion. The mechanisms of elimination of PFC emulsions from the circulation
      are not completely understood and has yet to be evaluated.

PMID- 15152158
TI  - Validation of 4 French catheters for quantitative coronary analysis: in vivo
      variability assessment using 6 French guiding catheters as reference scaling
      devices.
AB  - Although numerous studies have established the utility of 4 F catheters for
      routine coronary angiography, its adequacy for automatic quantitative coronary
      analysis has not been previously assessed. METHODS: In 32 consecutive patients,
      coronary angiography was performed sequentially with 4 F diagnostic catheters and
      6 F guiding catheters after intracoronary nitroglycerin. A total of 43 lesions
      were evaluated for quantitative analysis using both types of catheter as scaling
      devices. Possible differences in the reference diameter, minimal luminal diameter
      and percent diameter stenosis were evaluated. All measurements were performed
      offline by the same operator and intraobserver variability estimation was
      performed by repeating the evaluation in 12 lesions randomly selected after 1
      month. RESULTS: The mean reference diameter was 2.98+/-0.48 mm, mean minimal
      luminal diameter was 1.00+/-0.52 mm and percent diameter stenosis was 67.1+/
      15.3%. Accuracy (mean difference of values) was 0.009 mm for reference diameter,
      0.005 mm for minimal luminal diameter and 0.25% for percent diameter stenosis.
      Precision (mean standard deviation of the differences) was 0.17 mm for reference
      diameter, 0.19 mm for minimal luminal diameter and 5.93% for percent stenosis.
      Linear correlation for these three variables was 0.94, 0.93 and 0.93,
      respectively. Intraobserver variability analysis showed similar values for
      accuracy, precision and linear correlation. CONCLUSIONS: Angiography with 4 F
      catheters allows adequate quantification of luminal diameters as compared to most
      accepted clinical standards. These results may have implications for the
      selection of diagnostic catheters for routine follow-up assessment of
      percutaneous coronary interventions.

PMID- 15152159
TI  - Transcatheter closure of secundum atrial septal defects with complex anatomy.
AB  - The aim of this study was to evaluate the feasibility, safety and efficacy of
      transcatheter closure of secundum atrial septal defects (ASD) in patients with
      complex anatomy. From September 1997 to July 2003, a total of 40 patients (median
      age, 34 years; 65% female) with complex ASDs, defined as the presence of a large
      defect (stretched diameter >26 mm) associated with a deficient rim (n=23);
      multiple defects (n=8); a multi-fenestrated septum (n=5); and defects associated
      with an aneurysmal septum irrespective of their size (n=4) underwent closure. The
      Helex device was used in 4 patients and the Amplatzer in the remaining. Two
      devices were implanted in 2 patients each. Implantation was unsuccessful in 5
      patients, with 4 having large defects associated with a deficient anterior rim
      and a floppy posterior septum. Occlusion was observed in 22 of 35 patients (63%)
      immediately after implantation and in 31 (89%) at a mean follow-up of 18+/-9
      months. No major complications occurred. Right ventricular end-diastolic
      dimensions (indexed for body surface area) decreased from 135+/-25% before
      closure to 124+/-15% 24 hours after closure, and to 92+/-12% after 12 months. Two
      patients with 2 distant defects and 2 patients with large defects remained with
      shunts (<4 mm) at the latest visit. Transcatheter closure of complex secundum
      ASDs was feasible, safe and effective; however, large defects associated with a
      deficient anterior rim and a floppy posterior septum may not be suitable for this
      approach.

PMID- 15152160
TI  - Percutaneous occlusion of complex atrial septal defects.

PMID- 15152161
TI  - Simple clinical risk stratification and the safety of ambulation two hours after
      6 French diagnostic heart catheterization.
AB  - Heart catheterization is frequently applied in patients with coronary artery
      disease for diagnostic and therapeutic implications. Using the femoral approach,
      post-procedure bed rest of 4 to 6 hours is recommended to prevent groin
      complications. This extended strict bed rest is associated with patient
      discomfort and increased medical costs, and interferes with more efficient
      catheterization laboratory management of referred outpatients. Accordingly, we
      tested a simple clinical approach to identify low-risk patients who may benefit
      from ambulation within two hours after sheath removal. Ninety-eight outpatients
      were stratified to early (time=1.5 to 2.0 hours; n=74) or conventional ambulation
      (time=4 to 5 hours; n=24) based on difficulties in obtaining arterial access,
      presence of oozing or hematoma after completing manual compression. Ecchymosis
      was the most frequent complication, noted in one early ambulated and three
      conventionally ambulated patients at hospital discharge and in eleven early
      ambulated and six conventionally ambulated patients at one-week follow-up. No
      large hematomas, retroperitoneal bleeding or need for blood transfusion occurred
      in any patients. Using simple clinical parameters, most outpatients who undergo
      elective diagnostic catheterization may benefit from safe early ambulation.

PMID- 15152162
TI  - Comparison of the radial and femoral approaches in left main PCI: a retrospective
      study.
AB  - Transradial percutaneous coronary intervention (PCI) is a safe and effective
      method of percutaneous revascularization. However, there are no data on the
      efficacy of the transradial approach in left main (LM) PCI. We studied 80
      patients (pts) who underwent LM PCI between February 1994 and January 2002, and
      compared the radial (27 pts) and femoral (53 pts) approaches. Patients were
      considered free of restenosis if they were free of angina and had a negative
      treadmill or nuclear imaging study 6 months post-PCI. Mean follow-up time was
      27.4+/-23.0 months. Reason for PCI (stable angina, unstable angina, acute
      myocardial infarction) and lesion location (ostial, mid, distal) were similar in
      both groups (p>0.05), whereas mean ejection fraction was higher in the radial
      group (56.5+/-11.1% versus 49.2+/-14.7%, respectively; p<0.05). Sheath size (7 or
      8 French; 44.4% radial versus 77.3% femoral) and amount of heparin used (9,192+/
      3,645 IU versus 11,468+/-5,083 IU) were significantly larger in the femoral group
      (p<0.05), and the use of intra-aortic balloon pump was significantly more
      frequent (3.7% versus 22.6%). Mean fluoroscopy time (21.3+/-12.8 minutes versus
      16.7+/-8.5 minutes), amount of contrast used (227+/-92 ml versus 225+/-85 ml),
      mean procedural time (67.0+/-27.6 minutes versus 73.4+/-32.7 minutes), procedure
      success (96.3% versus 98.1%), in-hospital major adverse cardiac events (MACE;
      7.4% versus 5.6%) and 6-month MACE (14.8% versus 25.5%) were similar in the 2
      groups (p>0.05). However, major vascular complications occurred only in the
      femoral group (5.7%). Radial LM PCI is as fast and successful as the femoral
      approach and results in fewer vascular complications.

PMID- 15152163
TI  - Cutting balloon angioplasty to treat carotid in-stent restenosis.
AB  - We describe a case of carotid artery restenosis following carotid artery stenting
      for treatment of post-endarterectomy stenosis. The goal is to highlight the risk
      of recurrent restenosis following endarterectomy. In this case report, we
      describe the use of cutting balloon therapy as a reasonable alternative to repeat
      surgical revascularization.

PMID- 15152165
TI  - Severe intravascular hemolysis following mitral valve repair.
AB  - We report two cases of severe intravascular hemolysis (IVH) following mitral
      valve repair using a Cosgrove-Edwards ring. In both cases, the degree of mitral
      regurgitation (MR) seen postoperatively worsened significantly compared to
      intraoperative transesophageal echocardiogram. Both patients required reoperation
      with mitral valve replacement with immediate resolution of the hemolysis. We
      hypothesize that the mitral regurgitation in the setting of an inadequate mitral
      valve repair is responsible for the hemolysis and propose various mechanisms to
      explain this pathophysiology. Although IVH remains a rare complication following
      mitral valve repair, possible screening recommendations should be considered for
      early detection and treatment given the growing number of mitral valve repairs
      being performed.

PMID- 15152164
TI  - Low-molecular-weight heparins and glycoprotein IIb/IIIa antagonists in acute
      coronary syndromes.
AB  - Traditional antithrombotic regimens for the management of acute coronary
      syndromes are far from optimal. There is considerable opportunity for improvement
      of standard treatment with unfractionated heparin and aspirin. The introduction
      of new antithrombotic drugs, such as low-molecular-weight heparins(LMWH), and
      more potent antiplatelet drugs, such as glycoprotein(GP) lIb/llla antagonists,
      has the potential to significantly improve clinical outcomes. The complementary
      anticoagulant/antiplatelet modes of action of LMWHs and GP lIb/Ila antagonists
      mean that combining these drugs in the medical management of patients with acute
      coronary syndromes, including those who undergo percutaneous coronary
      intervention, may offer enhanced clinical benefits. Until recently, there was a
      lack of clinical data to support this approach, but several recent trials have
      confirmed the safety and efficacy of combination therapy with the LMWH enoxaparin
      and a GP lIb/Illa antagonist in the management of patients with unstable
      angina/non-ST segment elevation myocardial infarction. The 2002 American College
      of Cardiology/American Heart Association guidelines on unstable angina/non-ST
      segment elevation myocardial infarction reflect this new evidence. The combined
      use of a LMWH and a GP IIb/IIIa antagonist should now be viewed as safe and
      effective in the management of acute coronary syndromes. Definitive efficacy
      powered superiority data will be available shortly.

PMID- 15152167
TI  - Use of PercuSurge GuardWire in native coronary arteries during acute myocardial
      infarction.

PMID- 15152166
TI  - Stent implantation for coronary aneurysm with edge stenosis: angiographic and
      intravascular analysis.
AB  - The incidence of coronary artery aneurysms is about 1 to 2%, with clinical course
      dependent on the size of the aneurysm. A case of moderate-size aneurysm in the
      proximal left anterior descending coronary artery with stenosis at both edges is
      presented. This was interrogated with intravascular ultrasound (IVUS), and based
      on the patient's presentation, a single stent, size-matched 1:1 to the proximal
      reference, was placed across the aneurysm and both lesions. Post-implantation
      IVUS demonstrated residual stenosis and minimal change in the neck size of the
      aneurysm. At 4 months, there was no thrombosis or in-stent restenosis, and the
      aneurysm was almost completely resolved.

PMID- 15152169
TI  - Primary stenting of an anomalous left main trunk originating from the right
      coronary artery during acute myocardial infarction.
AB  - In 1.5 to 2.0% of patients with AMI referred for primary percutaneous coronary
      intervention, the left main trunk is identified as the culprit vessel. Among the
      congenital coronary anomalies, an anomalous origin of the left main trunk from
      the right sinus of Valsalva is very rare. A 73-year-old patient with lateral
      acute myocardial infarction was referred to primary angioplasty. The initial
      angiogram showed an anomalous origin of the left main from the right coronary
      artery, apparently with a septal course, with an angiographic image of
      intraluminal thrombus; in addition, a severe lesion was present at the distal
      right coronary artery. The left main and right coronary arteries were
      successfully treated with direct stenting. The subsequent clinical course during
      hospitalization was uneventful, and the patient was discharged alive.

PMID- 15152168
TI  - Intracoronary brachytherapy for in-stent restenosis of the left anterior
      descending artery via the left internal mammary artery using the galileo
      centering catheter.

PMID- 15152170
TI  - One stent lost in two arteries.

PMID- 15152171
TI  - Management of a patient with ST segment elevation myocardial infarction
      immediately after successful coiling of a basilar tip aneurysm for a subarachnoid
      hemorrhage.

PMID- 15152173
TI  - Coffee linked to reduced risk of diabetes.

PMID- 15152172
TI  - Cholesterol. The lowdown on this fatty substance.

PMID- 15152174
TI  - Azelaic acid, a new treatment for rosacea.

PMID- 15152175
TI  - Breathing exercise may ease asthma symptoms.

PMID- 15152176
TI  - Chronic obstructive pulmonary disease. Increased awareness leads to earlier
      treatment.

PMID- 15152177
TI  - Factoring in fiber. The good carbs.

PMID- 15152179
TI  - Pedometers. Stepping up your health.

PMID- 15152180
TI  - One on one. Now that I know about the negative effects of hormone therapy for
      women after menopause, do I need to be concerned that I took birth control pills
      earlier in my life? And do I need to be concerned that my daughter is now taking
      the pill?

PMID- 15152181
TI  - Mayo Clinic office visit. Acquiring your medicines safely.

PMID- 15152183
TI  - Fatal cases of Rocky Mountain spotted fever in family clusters--three states,
      2003.
AB  - Rocky Mountain spotted fever (RMSF), a tickborne infection caused by Rickettsia
      rickettsii and characterized by a rash, has a case-fatality rate as high as 30%
      in certain untreated patients. Even with treatment, hospitalization rates of 72%
      and case-fatality rates of 4% have been reported. This report summarizes the
      clinical course of three fatal cases of RMSF in children and related illness in
      family members during the summer of 2003. These cases underscore the importance
      of 1) prompt diagnosis and appropriate antimicrobial therapy in patients with
      RMSF to prevent deaths and 2) consideration of RMSF as a diagnosis in family
      members and contacts who have febrile illness and share environmental exposures
      with the patient.

PMID- 15152182
TI  - Youth risk behavior surveillance--United States, 2003.
AB  - PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the
      leading causes of morbidity and mortality among youth and adults, often are
      established during youth, extend into adulthood, are interrelated, and are
      preventable. REPORTING PERIOD: This report covers data collected during February
      December 2003. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System
      (YRBSS) monitors six categories of priority health-risk behaviors among youth and
      young adults--behaviors that contribute to unintentional injuries and violence;
      tobacco use; alcohol and other drug use; sexual behaviors that contribute to
      unintended pregnancy and sexually transmitted diseases (STDs), including human
      immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical
      inactivity--plus overweight. YRBSS includes a national school-based survey
      conducted by CDC as well as state and local school-based surveys conducted by
      education and health agencies. This report summarizes results from the national
      survey, 32 state surveys, and 18 local surveys conducted among students in grades
      9-12 during February-December 2003. RESULTS AND INTERPRETATION: In the United
      States, 70.8% of all deaths among persons aged 10-24 years result from only four
      causes: motor-vehicle crashes, other unintentional injuries, homicide, and
      suicide. Results from the 2003 national Youth Risk Behavior Survey demonstrated
      that, during the 30 days preceding the survey, numerous high school students
      engage in behaviors that increase their likelihood of death from these four
      causes: 30.2% had ridden with a driver who had been drinking alcohol; 17.1% had
      carried a weapon; 44.9% had drunk alcohol; and 22.4% had used marijuana. In
      addition, during the 12 months preceding the survey, 33.0% of high school
      students had been in a physical fight, and 8.5% had attempted suicide.
      Substantial morbidity and social problems among young persons also result from
      unintended pregnancies and STDs, including HIV infection. In 2003, 46.7% of high
      school students had ever had sexual intercourse; 37% of sexually active students
      had not used a condom at last sexual intercourse; and 3.2% had ever injected an
      illegal drug. Among adults aged > or =25 years, 62.9% of all deaths results from
      two causes: cardiovascular diseases and cancer. Results from the 2003 national
      Youth Risk Behavior Survey demonstrate that the majority of risk behaviors
      associated with these two causes of death are initiated during adolescence. In
      2003, a total of 21.9% of high school students had smoked cigarettes during the
      30 days preceding the survey; 78% had not eaten > or =5 servings/day of fruits
      and vegetables during the 7 days preceding the survey; 33.4% had participated in
      an insufficient amount of physical activity; and 13.5% were overweight. ACTIONS
      TAKEN: YRBSS data are being used to measure progress toward achieving 15 national
      health objectives for 2010 and three of the 10 leading health indicators. In
      addition, education and health officials at national, state, and local levels are
      using these YRBSS data to improve policies and programs to reduce priority health
      risk behaviors among youth.

PMID- 15152184
TI  - Multifocal autochthonous transmission of malaria--Florida, 2003.
AB  - The majority of malaria cases diagnosed in the United States are imported,
      usually by persons traveling from areas where malaria is endemic. However, small
      outbreaks of locally acquired mosquito-borne malaria continue to occur. During
      July-September 2003, an outbreak of malaria (eight cases of Plasmodium vivax
      malaria) occurred in Palm Beach County, Florida. During the same period, two
      patients were evaluated for malaria in neighboring Okeechobee County,
      approximately 75 miles from the Palm Beach County transmission area. One patient
      was thought to have acquired infection with the same parasite species (P. vivax),
      and concerns were raised about a possible link. To determine whether infection
      was acquired in Okeechobee County and whether a possible link existed to the Palm
      Beach County outbreak, the Florida Department of Health (FDOH) initiated an
      investigation. This report describes that investigation, which determined that
      although initial laboratory results suggested local transmission, subsequent
      evaluation and testing confirmed the case as imported malaria. These findings
      underscore the importance of a rapid and thorough investigation of any malaria
      case suspected to be acquired through local mosquito-borne transmission.

PMID- 15152185
TI  - Inward rectifying currents stabilize the membrane potential in dendrites of mouse
      amacrine cells: patch-clamp recordings and single-cell RT-PCR.
AB  - PURPOSE: To explore the possible existence of inward rectifying currents in the
      distal dendrites of amacrine cells. METHODS: Patch-clamp recordings were made
      from amacrine cells in a new horizontal slice preparation of mouse retina. Single
      cell RT-PCR studies were performed after the patch-clamp recordings. RESULTS: In
      contrast to results from vertical slices or dissociated cells, all amacrine cells
      tested demonstrated inward rectifying currents, IIR. Within the limits of our
      sample, this current did not depend on the morphological and physiological type
      of the amacrine cell. Amacrine cells from which the dendrites had been removed
      did not possess detectable amounts of IIR. Pharmacological experiments with
      ZD7288 (100 microM) and single-cell RT-PCR from recorded cells revealed that IIR
      includes an h-current (I(H)) carried by hyperpolarization-activated cyclic
      nucleotide gated channels (HCN), HCN1 and/or HCN2 subtypes. In the presence of
      extracellular Cs+ (5 mM), which greatly suppressed IIR, the resting membrane
      conductance was reduced. IIR suppressed the generation of oscillatory potentials.
      Intracellular cAMP (8-cpt-cAMP, 1 mM) activated IIR. CONCLUSIONS: IIR appears to
      occur within dendrites of many amacrine cells, where it tends to stabilize the
      resting membrane potential. HCN1 and/or HCN2 channels contribute to IIR in
      amacrine cells. Dendritic IIR would be expected to contribute to functional
      independence of the distal dendrites of amacrine cells that express it.

PMID- 15152186
TI  - Connexin 36 in photoreceptor cells: studies on transgenic rod-less and cone-less
      mouse retinas.
AB  - PURPOSE: Rod-cone gap junctions permit transmittal of rod visual information to
      the cone pathway. A recent report has shown that this transfer does not occur in
      mice in which the gap junction protein connexin 36 is knocked out indicating that
      rod-cone gap junctions are assembled from this protein. It remains unresolved,
      however, whether rods, cones or both express connexin 36. We have tried to
      address this question with the use of transgenic rod-less and cone-less mice.
      METHODS: Deletion of Nrl, a transcription factor, results in a complete loss of
      rods with a concomitant increase in S-cones. We used this as the rod-less (cone
      only) model. Cone-less (rod-only) retinas were from mice expressing an attenuated
      diphtheria toxin gene under the control of a promoter selective for cones. Nearly
      all long wavelength cones and 95% of short wavelength cones are missing in this
      model. Fixed retinal sections from these two models and age matched controls were
      used to detect connexin 36 gap junctions by immunofluorescence. RESULTS: Punctate
      immunofluorescence, indicating the presence of gap junctions, was observed in the
      inner and outer plexiform layers of both wild type and cone-less and rod-less
      retinas. Our assumption was that immunofluorescence due to photoreceptor gap
      junctions would be observed in the outer plexiform layer. In all the animals,
      most of the immunofluorescence was in the inner plexiform layer, with only a
      marginal reaction in the outer plexiform layer. In cone-only (rod-less) retina,
      immunofluorescence in the outer plexiform layer increased by more than 20 fold
      compared to wild type. In rod-only (cone-less) retina, the outer plexiform layer
      showed about a 30% decrease in immunofluorescence. In both rod-less and cone-less
      retinas, immunofluorescence in the inner plexiform layer was higher than in the
      wild type by 25-50%. CONCLUSIONS: Cones constitute only about 3% of
      photoreceptors in the wild type retina while they make up 100% of the
      photoreceptors in cone-only retina. This increase in their numbers coincided with
      a 20 fold increase in immunofluorescence in the outer plexiform layer, strongly
      suggesting that cones express connexin 36. Conversely, when the cone numbers went
      down from 3% to near zero in cone-less retina, immunofluorescence decreased by
      about 30% in the outer plexiform layer, suggesting again that cones express the
      connexin and that they contribute to its presence disproportionately more than
      their numbers indicate. The results from both rod-less and cone-less animals are
      strongly indicative of cones expressing connexin 36, but are not sufficient to
      conclude whether rods express the protein. An unexpected observation from our
      experiments is that immunofluorescence increases slightly in the inner plexiform
      layer in both rod-less and cone-less retina for reasons that need further
      investigation.

PMID- 15152187
TI  - Tight regulation from a single tet-off rAAV vector as demonstrated by flow
      cytometry and quantitative, real-time PCR.
AB  - Vectors suitable for delivery of therapeutic genes to the CNS for chronic
      neurodegenerative diseases will require regulatable transgene expression. In this
      study, three self-regulating rAAV vectors encoding humanized green fluorescent
      protein (hGFP) were made using the tetracycline (tet)-off system. Elements were
      cloned in different orientations relative to each other and to the AAV internal
      terminal repeat (ITRs). The advantage of this vector system is that all infected
      cells will carry both the 'therapeutic' gene and the tet-regulator. To compare
      the efficiency of the vectors, 293T cells infected by each vector were grown in
      the presence or absence of the tet-analog doxycycline (dox). Cells were analyzed
      by flow cytometry for hGFP protein expression, and quantitative RT-PCR (QRT-PCR)
      for levels of hGFP mRNA and the tet-activator (tTA) mRNA. In the presence of dox,
      cells infected with one of the vectors, rAAVS3, showed less than 2% total
      fluorescent intensity and mRNA copy number than cells grown without dox. The
      other two vectors were significantly more leaky. Levels of tTA mRNA were not
      affected by dox. The S3 vector also displayed tight regulation in HeLa and HT1080
      cells. To assess regulation in the brain, the S3 vector was injected into rat
      striatum and rats maintained on regular or dox-supplemented water. At 1 month
      after vector injection, numerous positive cells were observed in rats maintained
      on regular water whereas only rare positive cells with very low levels of
      fluorescence were observed in rats maintained on water containing dox. The QRT
      PCR analysis showed that dox inhibited expression of hGFP mRNA in brain by
      greater than 99%. These results demonstrate that exceedingly tight regulation of
      transgene expression is possible using the tet-off system in the context of a
      self-regulating rAAV vector and that the specific orientation of two promoters
      relative to each other and to the ITRs is important. Regulatable vectors based on
      this design are ideal for therapeutic gene delivery to the CNS.

PMID- 15152188
TI  - Uncoupling retro-translocation and degradation in the ER-associated degradation
      of a soluble protein.
AB  - Aberrant polypeptides in the endoplasmic reticulum (ER) are retro-translocated to
      the cytoplasm and degraded by the 26S proteasome via ER-associated degradation
      (ERAD). To begin to resolve the requirements for the retro-translocation and
      degradation steps during ERAD, a cell-free assay was used to investigate the
      contributions of specific factors in the yeast cytosol and in ER-derived
      microsomes during the ERAD of a model, soluble polypeptide. As ERAD was
      unaffected when cytoplasmic chaperone activity was compromised, we asked whether
      proteasomes on their own supported both export and degradation in this system.
      Proficient ERAD was observed if wild-type cytosol was substituted with either
      purified yeast or mammalian proteasomes. Moreover, addition of only the 19S cap
      of the proteasome catalyzed ATP-dependent export of the polypeptide substrate,
      which was degraded upon subsequent addition of the 20S particle.

PMID- 15152189
TI  - A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven
      motility in neurons.
AB  - Neuronal transmission of information requires polarized distribution of membrane
      proteins within axonal compartments. Membrane proteins are synthesized and
      packaged in membrane-bounded organelles (MBOs) in neuronal cell bodies and later
      transported to axons by microtubule-dependent motor proteins. Molecular
      mechanisms underlying targeted delivery of MBOs to discrete axonal subdomains
      (i.e. nodes of Ranvier or presynaptic terminals) are poorly understood, but
      regulatory pathways for microtubule motors may be an essential step. In this
      work, pharmacological, biochemical and in vivo experiments define a novel
      regulatory pathway for kinesin-driven motility in axons. This pathway involves
      enzymatic activities of cyclin-dependent kinase 5 (CDK5), protein phosphatase 1
      (PP1) and glycogen synthase kinase-3 (GSK3). Inhibition of CDK5 activity in axons
      leads to activation of GSK3 by PP1, phosphorylation of kinesin light chains by
      GSK3 and detachment of kinesin from transported cargoes. We propose that
      regulating the activity and localization of components in this pathway allows
      nerve cells to target organelle delivery to specific subcellular compartments.
      Implications of these findings for pathogenesis of neurodegenerative diseases
      such as Alzheimer's disease are discussed.

PMID- 15152190
TI  - Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1
      deacetylase.
AB  - NF-kappaB is responsible for upregulating gene products that control cell
      survival. In this study, we demonstrate that SIRT1, a nicotinamide adenosine
      dinucleotide-dependent histone deacetylase, regulates the transcriptional
      activity of NF-kappaB. SIRT1, the mammalian ortholog of the yeast SIR2 (Silencing
      Information Regulator) and a member of the Sirtuin family, has been implicated in
      modulating transcriptional silencing and cell survival. SIRT1 physically
      interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by
      deacetylating RelA/p65 at lysine 310. Treatment of cells with resveratrol, a
      small-molecule agonist of Sirtuin activity, potentiates chromatin-associated
      SIRT1 protein on the cIAP-2 promoter region, an effect that correlates with a
      loss of NF-kappaB-regulated gene expression and sensitization of cells to
      TNFalpha-induced apoptosis. While SIRT1 is capable of protecting cells from p53
      induced apoptosis, our work provides evidence that SIRT1 activity augments
      apoptosis in response to TNFalpha by the ability of the deacetylase to inhibit
      the transactivation potential of the RelA/p65 protein.

PMID- 15152191
TI  - Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled
      in the endoplasmic reticulum.
AB  - The T-cell receptor (TCR)-CD3 complex is critical for T-cell development and
      function, and represents one of the most complex transmembrane receptors. Models
      of different stoichiometry and valency have been proposed based on cellular
      experiments and these have important implications for the mechanisms of receptor
      triggering. Since determination of receptor stoichiometry in T-cells is not
      possible due to the presence of previously synthesized, unlabeled receptor
      components with different half-lives, we examined the stoichiometry of the
      receptor assembled in endoplasmic reticulum (ER) microsomes of B-cell origin. The
      stoichiometric relationship among all subunits was directly determined using
      intact radiolabeled TCR-CD3 complexes that were isolated with a sequential, non
      denaturing immunoprecipitation method, and identical results were obtained with
      two detergents belonging to different structural classes. The results firmly
      establish that the alphabeta TCR-CD3 complex assembled in the ER is monovalent
      and composed of one copy of the TCRalphabeta, CD3deltaepsilon, CD3gammaepsilon
      and zeta-zeta dimers.

PMID- 15152192
TI  - A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and
      HIV-2 Vif proteins.
AB  - The HIV-1 Vif protein suppresses the inhibition of viral replication caused by
      the human antiretroviral factor APOBEC3G. As a result, HIV-1 mutants that do not
      express the Vif protein are replication incompetent in 'nonpermissive' cells,
      such as primary T cells and the T-cell line CEM, that express APOBEC3G. In
      contrast, Vif-defective HIV-1 replicates effectively in 'permissive' cell lines,
      such as a derivative of CEM termed CEM-SS, that do not express APOBEC3G. Here, we
      show that a second human protein, APOBEC3F, is also specifically packaged into
      HIV-1 virions and inhibits their infectivity. APOBEC3F binds the HIV-1 Vif
      protein specifically and Vif suppresses both the inhibition of virus infectivity
      caused by APOBEC3F and virion incorporation of APOBEC3F. Surprisingly, APOBEC3F
      and APOBEC3G are extensively coexpressed in nonpermissive human cells, including
      primary lymphocytes and the cell line CEM, where they form heterodimers. In
      contrast, both genes are quiescent in the permissive CEM derivative CEM-SS.
      Together, these data argue that HIV-1 Vif has evolved to suppress at least two
      distinct but related human antiretroviral DNA-editing enzymes.

PMID- 15152194
TI  - HIF1 and oxygen sensing in the brain.

PMID- 15152193
TI  - Essential role of ribosomal protein L11 in mediating growth inhibition-induced
      p53 activation.
AB  - The ribosomal protein L11 binds to and suppresses the E3 ligase function of HDM2,
      thus activating p53. Despite being abundant as a component of the 60S large
      ribosomal subunit, L11 does not induce p53 under normal growth conditions. In
      search of mechanisms controlling L11-HDM2 interaction, we found that the
      induction of p53 under growth inhibitory conditions, such as low dose of
      actinomycin D or serum depletion, can be significantly attenuated by knocking
      down L11, indicating the importance of L11 in mediating these growth inhibitory
      signals to p53. We show that L11 is not regulated by transcription or protein
      stability and its level remains relatively constant during serum starvation.
      However, serum starvation induces translocation of L11 from the nucleolus to the
      nucleoplasm, where it participates in a complex with HDM2. We propose that the
      nucleolus acts as a barrier to prevent L11 interacting with HDM2 during normal
      growth. Growth inhibition, presumably through suppression of rRNA production in
      the nucleolus, facilitates translocation of L11 to the nucleoplasm, thus
      activating p53 through inhibiting HDM2.

PMID- 15152195
TI  - Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis.

PMID- 15152196
TI  - Merlin and the ERM proteins in Schwann cells, neurons and growth cones.

PMID- 15152197
TI  - Neurobiology of intelligence: science and ethics.

PMID- 15152198
TI  - Dopamine, learning and motivation.

PMID- 15152199
TI  - What attributes guide the deployment of visual attention and how do they do it?

PMID- 15152200
TI  - Different strategies for midline formation in bilaterians.

PMID- 15152201
TI  - Using nanotechniques to explore microbial surfaces.

PMID- 15152202
TI  - Dimerization of retroviral RNA genomes: an inseparable pair.

PMID- 15152203
TI  - Polio eradication, cessation of vaccination and re-emergence of disease.

PMID- 15152204
TI  - Small change: keeping pace with microevolution.

PMID- 15152205
TI  - Can innate immunity be enhanced to treat microbial infections?

PMID- 15152206
TI  - Salmonella, stress responses and food safety.

PMID- 15152208
TI  - Future shock.

PMID- 15152207
TI  - From pieces to patterns: evolutionary engineering in bacterial pathogens.

PMID- 15152209
TI  - Equal treatment under the law.

PMID- 15152210
TI  - Iranian physicist locked out of laboratory by energy department.

PMID- 15152211
TI  - Health assembly rebuffs Taiwan's bid for 'observer' status.

PMID- 15152213
TI  - Software company bans competitive users.

PMID- 15152212
TI  - Panel slated for leniency over study of NIH consulting roles.

PMID- 15152214
TI  - Charging plan casts a shadow on Japan's light beam.

PMID- 15152215
TI  - Talks pave way for docking between Russia and ESA.

PMID- 15152216
TI  - Germany backs genome networks to tackle diseases.

PMID- 15152217
TI  - Big buzz as cicadas arrive after 17-year gap.

PMID- 15152218
TI  - Britain plans laws to restrain animal-rights activists.

PMID- 15152219
TI  - US changes rules to speed up approval of AIDS drug cocktails.

PMID- 15152220
TI  - Giardia: not so special, after all?

PMID- 15152221
TI  - Energy: nuclear power's new dawn.

PMID- 15152222
TI  - Autistic geniuses? We're too ready to pathologize.

PMID- 15152223
TI  - Bioinformatics: smartest software is still just a tool.

PMID- 15152224
TI  - Bioinformatics needs a software archive.

PMID- 15152230
TI  - Last hideout of the unknown?

PMID- 15152231
TI  - Reproductive biology: pillow talk in plants.

PMID- 15152233
TI  - Condensed-matter physics: atomic beads on strings of light.

PMID- 15152232
TI  - Planetary science: a perfect match?

PMID- 15152234
TI  - Malaria: the calcium connection.

PMID- 15152237
TI  - Chemistry: atom tracking.

PMID- 15152235
TI  - Gene regulation: selfish elements make a mark.

PMID- 15152238
TI  - Solar System: Captain Cook and the black drop.

PMID- 15152239
TI  - Obituary: John Maynard Smith (1920-2004).

PMID- 15152241
TI  - Red deer stocks in the Highlands of Scotland.
AB  - Grazing by hill sheep and red deer prevents the regeneration of woodland in many
      parts of the Scottish Highlands and has also led to extensive loss of heather
      cover. Conservation bodies claim that there has been a rapid rise in Highland
      deer numbers caused by inadequate management and that these need to be
      drastically reduced. Here we show that the recent increase in red deer stocks has
      probably been overestimated and suggest that the gradual rise in numbers since
      1970 may be a consequence of a reduction in sheep stocks and of changes in winter
      weather, rather than of a reduction in culling rate. Although there would be
      environmental benefits in reducing deer numbers, there is an equal need to reduce
      the numbers of hill sheep in many parts of the Highlands.

PMID- 15152242
TI  - Vision: steady-state misbinding of colour and motion.
AB  - When you see a red ball rolling across the floor, the ball's redness, roundness
      and motion appear to be unified and inseparably bound together as features of the
      ball. But neurophysiological evidence indicates that visual features such as
      colour, shape and motion are processed in separate regions of the brain. Here we
      describe an illusion that exploits this separation, causing colour and motion to
      be recombined incorrectly while a stable stimulus is being viewed continuously.

PMID- 15152244
TI  - Regional climate shifts caused by gradual global cooling in the Pliocene epoch.
AB  - The Earth's climate has undergone a global transition over the past four million
      years, from warm conditions with global surface temperatures about 3 degrees C
      warmer than today, smaller ice sheets and higher sea levels to the current cooler
      conditions. Tectonic changes and their influence on ocean heat transport have
      been suggested as forcing factors for that transition, including the onset of
      significant Northern Hemisphere glaciation approximately 2.75 million years ago,
      but the ultimate causes for the climatic changes are still under debate. Here we
      compare climate records from high latitudes, subtropical regions and the tropics,
      indicating that the onset of large glacial/interglacial cycles did not coincide
      with a specific climate reorganization event at lower latitudes. The regional
      differences in the timing of cooling imply that global cooling was a gradual
      process, rather than the response to a single threshold or episodic event as
      previously suggested. We also find that high-latitude climate sensitivity to
      variations in solar heating increased gradually, culminating after cool tropical
      and subtropical upwelling conditions were established two million years ago. Our
      results suggest that mean low-latitude climate conditions can significantly
      influence global climate feedbacks.

PMID- 15152245
TI  - Transcriptional disruption by the L1 retrotransposon and implications for
      mammalian transcriptomes.
AB  - LINE-1 (L1) elements are the most abundant autonomous retrotransposons in the
      human genome, accounting for about 17% of human DNA. The L1 retrotransposon
      encodes two proteins, open reading frame (ORF)1 and the ORF2 endonuclease/reverse
      transcriptase. L1 RNA and ORF2 protein are difficult to detect in mammalian
      cells, even in the context of overexpression systems. Here we show that inserting
      L1 sequences on a transcript significantly decreases RNA expression and therefore
      protein expression. This decreased RNA concentration does not result from major
      effects on the transcription initiation rate or RNA stability. Rather, the poor
      L1 expression is primarily due to inadequate transcriptional elongation. Because
      L1 is an abundant and broadly distributed mobile element, the inhibition of
      transcriptional elongation by L1 might profoundly affect expression of endogenous
      human genes. We propose a model in which L1 affects gene expression genome-wide
      by acting as a 'molecular rheostat' of target genes. Bioinformatic data are
      consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of
      the human transcriptome.

PMID- 15152246
TI  - An age-colour relationship for main-belt S-complex asteroids.
AB  - Asteroid collisions in the main belt eject fragments that may eventually land on
      Earth as meteorites. It has therefore been a long-standing puzzle in planetary
      science that laboratory spectra of the most populous class of meteorite (ordinary
      chondrites, OC) do not match the remotely observed surface spectra of their
      presumed (S-complex) asteroidal parent bodies. One of the proposed solutions to
      this perplexing observation is that 'space weathering' modifies the exposed
      planetary surfaces over time through a variety of processes (such as solar and
      cosmic ray bombardment, micro-meteorite bombardment, and so on). Space weathering
      has been observed on lunar samples, in Earth-based laboratory experiments, and
      there is good evidence from spacecraft data that the process is active on
      asteroid surfaces. Here, we present a measurement of the rate of space weathering
      on S-complex main-belt asteroids using a relationship between the ages of
      asteroid families and their colours. Extrapolating this age-colour relationship
      to very young ages yields a good match to the colour of freshly cut OC meteorite
      samples, lending strong support to a genetic relationship between them and the S
      complex asteroids.

PMID- 15152247
TI  - Tonks-Girardeau gas of ultracold atoms in an optical lattice.
AB  - Strongly correlated quantum systems are among the most intriguing and fundamental
      systems in physics. One such example is the Tonks-Girardeau gas, proposed about
      40 years ago, but until now lacking experimental realization; in such a gas, the
      repulsive interactions between bosonic particles confined to one dimension
      dominate the physics of the system. In order to minimize their mutual repulsion,
      the bosons are prevented from occupying the same position in space. This mimics
      the Pauli exclusion principle for fermions, causing the bosonic particles to
      exhibit fermionic properties. However, such bosons do not exhibit completely
      ideal fermionic (or bosonic) quantum behaviour; for example, this is reflected in
      their characteristic momentum distribution. Here we report the preparation of a
      Tonks-Girardeau gas of ultracold rubidium atoms held in a two-dimensional optical
      lattice formed by two orthogonal standing waves. The addition of a third,
      shallower lattice potential along the long axis of the quantum gases allows us to
      enter the Tonks-Girardeau regime by increasing the atoms' effective mass and
      thereby enhancing the role of interactions. We make a theoretical prediction of
      the momentum distribution based on an approach in which trapped bosons acquire
      fermionic properties, finding that it agrees closely with the measured
      distribution.

PMID- 15152248
TI  - Synthesis and characterization of chiral mesoporous silica.
AB  - Chirality is widely expressed in organic materials, perhaps most notably in
      biological molecules such as DNA, and in proteins, owing to the homochirality of
      their components (d-sugars and l-amino acids). But the occurrence of large-scale
      chiral pores in inorganic materials is rare. Although some progress has been made
      in strategies to synthesize helical and chiral zeolite-like materials, the
      synthesis of enantiomerically pure mesoporous materials is a challenge that
      remains unsolved. Here we report the surfactant-templated synthesis of ordered
      chiral mesoporous silica, together with a general approach for the structural
      analysis of chiral mesoporous crystals by electron microscopy. The material that
      we have synthesized has a twisted hexagonal rod-like morphology, with diameter
      130-180 nm and length 1-6 micro m. Transmission electron microscopy combined with
      computer simulations confirm the presence of hexagonally ordered chiral channels
      of 2.2 nm diameter winding around the central axis of the rods. Our findings
      could lead to new uses for mesoporous silica and other chiral pore materials in,
      for example, catalysis and separation media, where both shape selectivity and
      enantioselectivity can be applied to the manufacturing of enantiomerically pure
      chemicals and pharmaceuticals.

PMID- 15152249
TI  - Analysing the 1811-1812 New Madrid earthquakes with recent instrumentally
      recorded aftershocks.
AB  - Although dynamic stress changes associated with the passage of seismic waves are
      thought to trigger earthquakes at great distances, more than 60 per cent of all
      aftershocks appear to be triggered by static stress changes within two rupture
      lengths of a mainshock. The observed distribution of aftershocks may thus be used
      to infer details of mainshock rupture geometry. Aftershocks following large mid
      continental earthquakes, where background stressing rates are low, are known to
      persist for centuries, and models based on rate-and-state friction laws provide
      theoretical support for this inference. Most past studies of the New Madrid
      earthquake sequence have indeed assumed ongoing microseismicity to be a
      continuing aftershock sequence. Here we use instrumentally recorded aftershock
      locations and models of elastic stress change to develop a kinematically
      consistent rupture scenario for three of the four largest earthquakes of the 1811
      1812 New Madrid sequence. Our results suggest that these three events occurred on
      two contiguous faults, producing lobes of increased stress near fault
      intersections and end points, in areas where present-day microearthquakes have
      been hitherto interpreted as evidence of primary mainshock rupture. We infer that
      the remaining New Madrid mainshock may have occurred more than 200 km north of
      this region in the Wabash Valley of southern Indiana and Illinois--an area that
      contains abundant modern microseismicity, and where substantial liquefaction was
      documented by historic accounts. Our results suggest that future large mid-plate
      earthquake sequences may extend over a much broader region than previously
      suspected.

PMID- 15152250
TI  - Articulated Palaeozoic fossil with 17 plates greatly expands disparity of early
      chitons.
AB  - Modern chitons (Mollusca: Polyplacophora) possess a highly conserved skeleton of
      eight shell plates (valves) surrounded by spicules or scales, and fossil evidence
      suggests that the chiton skeleton has changed little since the first appearance
      of the class in the Late Cambrian period (about 500 million years before present,
      Myr bp). However, the Palaeozoic problematic taxon Multiplacophora, in spite of
      having a more complex skeleton, shares several derived characters with chitons.
      The enigmatic status of the Multiplacophora is due in part to the fact that its
      members had an exoskeleton of numerous calcium carbonate valves that usually
      separated after death. A new articulated specimen from the Carboniferous period
      (about 335 Myr bp) of Indiana reveals that multiplacophorans had a dorsal
      protective surface composed of head and tail valves, left and right columns of
      overlapping valves (five on each side), and a central zone of five smaller
      valves, all surrounded by an annulus of large spines. Here we describe and name
      the articulated specimen and present evidence that multiplacophorans were
      chitons. Thus the highly conserved body plan of living chitons belies the broad
      disparity of this clade during the Palaeozoic era.

PMID- 15152251
TI  - Iron and phosphorus co-limit nitrogen fixation in the eastern tropical North
      Atlantic.
AB  - The role of iron in enhancing phytoplankton productivity in high nutrient, low
      chlorophyll oceanic regions was demonstrated first through iron-addition bioassay
      experiments and subsequently confirmed by large-scale iron fertilization
      experiments. Iron supply has been hypothesized to limit nitrogen fixation and
      hence oceanic primary productivity on geological timescales, providing an
      alternative to phosphorus as the ultimate limiting nutrient. Oceanographic
      observations have been interpreted both to confirm and refute this hypothesis,
      but direct experimental evidence is lacking. We conducted experiments to test
      this hypothesis during the Meteor 55 cruise to the tropical North Atlantic. This
      region is rich in diazotrophs and strongly impacted by Saharan dust input. Here
      we show that community primary productivity was nitrogen-limited, and that
      nitrogen fixation was co-limited by iron and phosphorus. Saharan dust addition
      stimulated nitrogen fixation, presumably by supplying both iron and phosphorus.
      Our results support the hypothesis that aeolian mineral dust deposition promotes
      nitrogen fixation in the eastern tropical North Atlantic.

PMID- 15152252
TI  - Evidence for ecology's role in speciation.
AB  - A principal challenge in testing the role of natural selection in speciation is
      to connect the build-up of reproductive isolation between populations to
      divergence of ecologically important traits. Demonstrations of 'parallel
      speciation', or assortative mating by selective environment, link ecology and
      isolation, but the phenotypic traits mediating isolation have not been confirmed.
      Here we show that the parallel build-up of mating incompatibilities between
      stickleback populations can be largely accounted for by assortative mating based
      on one trait, body size, which evolves predictably according to environment. In
      addition to documenting the influence of body size on reproductive isolation for
      stickleback populations spread across the Northern Hemisphere, we have confirmed
      its importance through a new experimental manipulation. Together, these results
      suggest that speciation may arise largely as a by-product of ecological
      differences and divergent selection on a small number of phenotypic traits.

PMID- 15152253
TI  - Identification of the pollen determinant of S-RNase-mediated self
      incompatibility.
AB  - Many flowering plants have adopted self-incompatibility mechanisms to prevent
      inbreeding and promote out-crosses. In the Solanaceae, Rosaceae and
      Scrophulariaceae, two separate genes at the highly polymorphic S-locus control
      self-incompatibility interactions: the S-RNase gene encodes the pistil
      determinant and the previously unidentified S-gene encodes the pollen
      determinant. S-RNases interact with pollen S-allele products to inhibit the
      growth of self-pollen tubes in the style. Pollen-expressed F-box genes showing
      allelic sequence polymorphism have recently been identified near to the S-RNase
      gene in members of the Rosaceae and Scrophulariaceae; but until now have not been
      directly shown to encode the pollen determinant. Here we report the
      identification and characterization of PiSLF, an S-locus F-box gene of Petunia
      inflata (Solanaceae). We show that transformation of S1S1, S1S2 and S2S3 plants
      with the S2-allele of PiSLF causes breakdown of their pollen function in self
      incompatibility. This breakdown of pollen function is consistent with
      'competitive interaction', in which pollen carrying two different pollen S
      alleles fails to function in self-incompatibility. We conclude that PiSLF encodes
      the pollen self-incompatibility determinant.

PMID- 15152254
TI  - Self-incompatibility triggers programmed cell death in Papaver pollen.
AB  - Sexual reproduction in many angiosperm plants involves self-incompatibility (SI),
      which is one of the most important mechanisms to prevent inbreeding. SI is
      genetically controlled by the S-locus, and involves highly specific interactions
      during pollination between pollen and the pistil on which it lands. This results
      in the rejection of incompatible ('self') pollen, whereas compatible ('non-self')
      pollen is allowed to fertilize the plant. In Papaver rhoeas, S-proteins encoded
      by the stigma component of the S-locus interact with incompatible pollen,
      triggering a Ca2+-dependent signalling network, resulting in the inhibition of
      pollen-tube growth. Programmed cell death (PCD) is a mechanism used by many
      organisms to destroy unwanted cells in a precisely regulated manner. Here we show
      that PCD is triggered by SI in an S-specific manner in incompatible pollen. This
      provides a demonstration of a SI system using PCD, revealing a novel mechanism to
      prevent self-fertilization. Furthermore, our data reveal that the response is
      biphasic; rapid inhibition of pollen-tube growth is followed by PCD, which is
      involved in a later 'decision-making' phase, making inhibition irreversible.

PMID- 15152255
TI  - Rab5 is a signalling GTPase involved in actin remodelling by receptor tyrosine
      kinases.
AB  - Rab5 is a small GTPase involved in the control of intracellular trafficking, both
      at the level of receptor endocytosis and endosomal dynamics. The finding that
      Rab5 can be activated by receptor tyrosine kinases (RTK) raised the question of
      whether it also participates in effector pathways emanating from these receptors.
      Here we show that Rab5 is indispensable for a form of RTK-induced actin
      remodelling, called circular ruffling. Three independent signals, originating
      from Rab5, phosphatidylinositol-3-OH kinase and Rac, respectively, are
      simultaneously required for the induction of circular ruffles. Rab5 signals to
      the actin cytoskeleton through RN-tre, a previously identified Rab5-specific
      GTPase-activating protein (GAP). Here we demonstrate that RN-tre has the dual
      function of Rab5-GAP and Rab5 effector. We also show that RN-tre is critical for
      macropinocytosis, a process previously connected to the formation of circular
      ruffles. Finally, RN-tre interacts with both F-actin and actinin-4, an F-actin
      bundling protein. We propose that RN-tre establishes a three-pronged connection
      with Rab5, F-actin and actinin-4. This may aid crosslinking of actin fibres into
      actin networks at the plasma membrane. Thus, we have shown that Rab5 is a
      signalling GTPase and have elucidated the major molecular elements of its
      downstream pathway.

PMID- 15152256
TI  - A highly active synthetic mammalian retrotransposon.
AB  - LINE-1 (L1) elements are retrotransposons that comprise large fractions of
      mammalian genomes. Transcription through L1 open reading frames is inefficient
      owing to an elongation defect, inhibiting the robust expression of L1 RNA and
      proteins, the substrate and enzyme(s) for retrotransposition. This elongation
      defect probably controls L1 transposition frequency in mammalian cells. Here we
      report bypassing this transcriptional defect by synthesizing the open reading
      frames of L1 from synthetic oligonucleotides, altering 24% of the nucleic acid
      sequence without changing the amino acid sequence. Such resynthesis led to
      greatly enhanced steady-state L1 RNA and protein levels. Remarkably, when the
      synthetic open reading frames were substituted for the wild-type open reading
      frames in an established retrotransposition assay, transposition levels increased
      more than 200-fold. This indicates that there are probably no large, rigidly
      conserved cis-acting nucleic acid sequences required for retrotransposition
      within L1 coding regions. These synthetic retrotransposons are also the most
      highly active L1 elements known so far and have potential as practical tools for
      manipulating mammalian genomes.

PMID- 15152258
TI  - Retraction: Unaltered cosmic spherules in a 1.4-Gyr-old sandstone from Finland.

PMID- 15152259
TI  - A delicate balance.

PMID- 15152257
TI  - Structural basis for overhang-specific small interfering RNA recognition by the
      PAZ domain.
AB  - Short RNAs mediate gene silencing, a process associated with virus resistance,
      developmental control and heterochromatin formation in eukaryotes. RNA silencing
      is initiated through Dicer-mediated processing of double-stranded RNA into small
      interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute
      protein in silencing effector complexes, recognizes complementary sequences and
      targets them for silencing. The PAZ domain is an RNA-binding module found in
      Argonaute and some Dicer proteins and its structure has been determined in the
      free state. Here, we report the 2.6 A crystal structure of the PAZ domain from
      human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a
      sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the
      siRNA-like duplex within a highly conserved binding pocket, and secures the
      duplex by binding the 7-nucleotide phosphodiester backbone of the overhang
      containing strand and capping the 5'-terminal residue of the complementary
      strand. On the basis of the structure and on binding assays, we propose that PAZ
      might serve as an siRNA-end-binding module for siRNA transfer in the RNA
      silencing pathway, and as an anchoring site for the 3' end of guide RNA within
      silencing effector complexes.

PMID- 15152260
TI  - From industry to academia.

PMID- 15152262
TI  - Bricks and mortar. Switzerland switches on supercomputers.

PMID- 15152264
TI  - The transcriptional programme of antibody class switching involves the repressor
      Bach2.
AB  - Activated B cells differentiate to plasma cells to secrete IgM or, after
      undergoing class switch recombination (CSR), to secrete other classes of
      immunoglobulins. Diversification of antibody function by CSR is important for
      humoral immunity. However, it remains unclear how the decision for the
      bifurcation is made. Bach2 is a B-cell-specific transcription repressor
      interacting with the small Maf proteins whose expression is high only before the
      plasma cell stage. Here we show that Bach2 is critical for CSR and somatic
      hypermutation (SHM) of immunoglobulin genes. Genetic ablation of Bach2 in mice
      revealed that Bach2 was required for both T-cell-independent and T-cell-dependent
      IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced
      IgM, as did wild-type cells, and abundantly expressed Blimp-1 (refs 9, 10) and
      XBP-1 (ref. 11), critical regulators of the plasmacytic differentiation,
      indicating that Bach2 was not required for the plasmacytic differentiation
      itself. However, they failed to undergo efficient CSR. These findings define
      Bach2 as a key regulator of antibody response and provide an insight into the
      orchestration of CSR and SHM during plasma cell differentiation.

PMID- 15152265
TI  - Biochemical pathway of antigen processing by HLA class II molecules in B cell
      lymphomas.

PMID- 15152267
TI  - Prediction of immunophenotype, treatment response, and relapse in childhood acute
      lymphoblastic leukemia using DNA microarrays.
AB  - Gene expression profiling is a promising tool for classification of pediatric
      acute lymphoblastic leukemia (ALL). We analyzed the gene expression at the time
      of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free
      survival or relapse after treatment by NOPHO-ALL92 or 2000 protocols resulted in
      a classification accuracy of 78% and a Matthew's correlation coefficient of 0.59
      independently of immunophenotypes. The sensitivity and specificity for prediction
      of relapse were 87% and 69% respectively. Prediction of high vs low levels of the
      minimal residual disease (MRD) on day 29 (>/=0.1% or </=0.01%) resulted in an
      accuracy of 100% for precursor-B samples. The classification accuracy of
      precursor-B- vs T-lineage immunophenotypes was 100% even in samples with as
      little as 10% leukemic blast cells, and the immunophenotype classifier
      constructed in this study was able to classify 131 of 132 samples from a previous
      study correctly. Our study indicates that the Affymetrix Focus Array GeneChip may
      be used without loss of classification performance compared to previous studies
      using the far more extensive U133A+B GeneChip set. Further studies should focus
      on prediction of MRD, as this prediction would relate strongly to long-term
      outcome and could thus determine the intensity of induction therapy.

PMID- 15152266
TI  - Cytosine arabinoside induces costimulatory molecule expression in acute myeloid
      leukemia cells.
AB  - Chemotherapeutic drugs kill cancer cells mainly by direct cytotoxicity, but they
      might also induce a stronger host immune response by causing the tumor to produce
      costimulatory cell surface molecules like CD80. We previously reported that in
      myeloid leukemic cells, gamma-irradiation induced CD80 expression. In this study,
      we show that cytosine arabinoside (Ara-C), even at low doses, induced CD80
      expression in vitro in mouse DA1-3b leukemic cells, by a mechanism that involved
      reactive oxygen species. In vivo experiments in the mouse DA1-3b/C3H whole-animal
      acute myeloid leukemia (AML) model showed that injection of Ara-C induced
      expression of CD80 and CD86, and decreased expression of B7-H1, indicating that
      chemotherapy can modify costimulatory molecule expression in vivo, in a way not
      necessarily observed in vitro. Mouse leukemic cells exposed in vivo to Ara-C were
      more susceptible to specific cytotoxic lymphocyte (CTL)-mediated killing. Ara-C
      also induced CD80 or CD86 expression in 14 of 21 primary cultured human AML
      samples. In humans being treated for AML, induction chemotherapy increased CD86
      expression in the leukemic cells. These findings indicate possible synergistic
      strategies between CTL-based immunotherapy and chemotherapy for treatment. They
      also suggest an additional mechanism by which chemotherapy can eradicate AML
      blasts.

PMID- 15152268
TI  - Role of CD44 variant exon 6 in acute lymphoblastic leukaemia: association with
      altered bone marrow localisation and increased tumour burden.

PMID- 15152269
TI  - Expression of AML1-ETO in human myelomonocytic cells selectively inhibits
      granulocytic differentiation and promotes their self-renewal.
AB  - The t(8;21) translocation is one of the most frequent translocations in acute
      myeloid leukaemia (AML), giving rise to the AML1-ETO fusion protein (or RUNX1
      CBF2T1). This abnormality is associated with myelocytic leukaemia with dysplastic
      granulopoiesis. Here, we demonstrate that when expressed in a normal human
      (CD34(+)) progenitor population, AML1-ETO selectively inhibits granulocyte colony
      formation but not monocyte colony formation. In bulk liquid culture, we found
      that though AML1-ETO transiently inhibited the proliferation of CD34(+) cells, it
      promoted long-term growth of myeloid cells for more than 80 days, suggesting that
      differentiation was inhibited. In support of this, cultures expressing AML1-ETO
      demonstrated enhanced retention of colony-forming capacity. Phenotypic
      examination of AML1-ETO cultures revealed a defect in granulocytic
      differentiation in terms of retention of CD34(+) cells within the culture and
      delayed CD11b upregulation. Morphologically, granulocyte terminal differentiation
      in AML1-ETO-expressing cells was inhibited by 83+/-5%, giving rise to a build-up
      of early to intermediate granulocytes that exhibited a number of morphological
      features associated with t(8;21) leukaemias. In contrast, AML1-ETO had little or
      no effect on monocytic differentiation. Taken together, these results suggest
      that expression of AML1-ETO selectively inhibits the differentiation of
      granulocytic cells and promoted extensive self-renewal, supporting a causal role
      for t(8;21) translocations in leukaemogenesis.

PMID- 15152270
TI  - Mifepristone: effect on plasma corticotropin-releasing hormone,
      adrenocorticotropic hormone, and cortisol in term pregnancy.
AB  - OBJECTIVE: To compare the effects of in vivo mifepristone with placebo on plasma
      corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and
      cortisol levels concentrations in term human pregnancies. STUDY DESIGN: In all,
      24 women participating in a randomized controlled trial of mifepristone for
      preinduction cervical ripening were enrolled in this ancillary study.
      Participants with uncomplicated singleton pregnancies beyond 41 weeks gestation
      and undilated, uneffaced cervices were randomized to either placebo or
      mifepristone 200 mg orally and observed for 24 hours prior to receiving either
      intravaginal misoprostol and/or intravenous oxytocin. Blood samples were obtained
      before medication administration, 3 and 6 hours later, and then every 6 hours
      until delivery. Plasma hormone levels were measured by radioimmunoassay. RESULTS:
      Basal levels of CRH, ACTH, and cortisol were similar in the placebo (n=13) and
      mifepristone groups (n=11). Compared to placebo treatment, exposure to
      mifepristone resulted in significant elevation of plasma cortisol within 18
      hours. Plasma CRH and ACTH were unaffected. Progression of labor was associated
      with significant increases in cortisol in both groups, while CRH and ACTH levels
      were not altered. Compared to basal levels within each group, plasma cortisol at
      delivery was significantly elevated within both the mifepristone (156.8+/-17.7 vs
      332.6+/-48.5 ng/ml, p=0.008) and the placebo (166.6+/-34.3 vs 342.4+/-46.4 ng/ml,
      p=0.003) groups. However, plasma CRH, ACTH, and cortisol levels at delivery did
      not differ between the groups. CONCLUSION: Mifepristone exposure and induced
      labor were associated with significant increases in plasma cortisol without
      alterations of systemic CRH or ACTH levels.

PMID- 15152272
TI  - The startle test revisited.
AB  - OBJECTIVE: Our purpose was to the compare fetal heart reaction to external
      physical stimulation with the nonstress test (NST). STUDY DESIGN: This
      prospective study evaluates documentation of fetal heart rate accelerations by
      two methods. The standard NST was performed prior to the ultrasound evaluation.
      The NST results were unavailable to the ultrasonographer. M-mode ultrasound was
      used initially to detect a stable heart rate. Then the ultrasound transducer was
      used to stimulate fetal movement by indenting the uterus over the fetal small
      parts. A second fetal heart rate was determined within 15 seconds after
      stimulation. RESULTS: A total of 194 patients underwent 235 studies. The patient
      population included four sets of twins. When the NST was reactive, 151/216 had an
      ultrasound startle response of > or =15 beats per minute; however, all
      nonreactive NSTs were associated with an ultrasound response of 14 beats per
      minute or less (p<0.001). A receiver-operating characteristic curve comparing the
      ultrasound fetal response to the startle with the NST identified the area under
      the curve to be 0.948, consistent with high specificity and sensitivity.
      CONCLUSION: The fetal heart rate response to external stimulation identifies 67%
      of patients with a reactive NST.

PMID- 15152271
TI  - Neonatal research and the validity of informed consent obtained in the perinatal
      period.
AB  - BACKGROUND: Consent for participation in clinical research is considered valid if
      it is informed, understood, and voluntary. In the case of minors, parents give
      permission for their child to participate in research studies after being
      presented with all information needed to make an informed decision. Although
      informed consent is a vital component of clinical research, there is little
      information evaluating its validity in neonatal intensive-care populations. The
      objective of this project was to determine the validity of informed consent
      obtained from parents of infants enrolled in the multicenter randomized research
      study, neurologic outcomes and pre-emptive analgesia in the neonate (NEOPAIN).
      DESIGN/METHODS: Parents of infants who survived to discharge and had signed
      consent for their newborn to participate in the NEOPAIN study at the University
      of Kentucky were asked 20 open-ended questions to determine their level of
      understanding about the NEOPAIN study. The NEOPAIN consent form, which had been
      approved by the University of Kentucky Medical Institutional Review Board (IRB),
      was used to formulate these questions. Questions addressed the timing of consent,
      parental understanding of the purpose, benefits, and risks of the study, the
      voluntary nature of the project, and their willingness to enroll in future
      studies if the opportunity presented. Answers were scored on a Likert scale, with
      1 for no understanding and 5 for complete understanding. RESULTS: Five of 64
      parents (7.8%) had no recollection of the NEOPAIN study or of signing consent. Of
      those who remembered the study, only 67.8% understood the purpose of the study,
      with a higher proportion of the mothers than fathers knowing the purpose of the
      study (73.3% vs 57.1%), (p=0.029). Of those who understood the purpose of the
      study 95% were able to verbalize the benefits, but only 5% understood any
      potential risks. No parents reported feeling pressured or coerced to sign consent
      for the project and all parents reported they would enroll their child in
      additional studies if asked. CONCLUSIONS: Valid consent in the
      antenatal/perinatal population is difficult, if not impossible, to obtain. To
      maximize validity of consent in the antenatal/perinatal population every effort
      should be made to include mothers in the consent process. Additional attention
      during the consent process should be given to possible risks of the study.

PMID- 15152273
TI  - Prospective observational study to establish predictors of glyburide success in
      women with gestational diabetes mellitus.
AB  - OBJECTIVE: To establish parameters associated with therapeutic success in
      gestational diabetics treated with glyburide. STUDY DESIGN: A total of 69
      gestational diabetics who failed dietary therapy were treated with glyburide.
      Inadequate glycemic control on maximum dose glyburide (10 mg b.i.d.) was
      considered treatment failure. The glyburide failure rate was calculated and
      factors that might predict success with glyburide were analyzed between the
      success and failure groups using chi(2) or Student'st-tests. RESULTS: The
      glyburide failure rate was 18.8%. Gestational age at glyburide initiation
      (p<0.01), pretreatment fasting blood sugars (p<0.001), and 1-hour postprandial
      values (p<0.001) were the only statistically significant factors between the two
      groups. Glyburide success was predicted if dietary failure occurred after 30
      weeks, or fasting blood sugars were <110 mg/dl and 1-hour postprandials were <140
      mg/dl (sensitivity 98%, specificity 65%). CONCLUSION: Gestational diabetics who
      fail dietary therapy after 30 weeks gestation or have fasting blood sugars <110
      mg/dl and 1-hour postprandials <140 mg/dl do well on glyburide therapy.

PMID- 15152274
TI  - Fertility options in young breast cancer survivors: a review of the literature.
AB  - PURPOSE/OBJECTIVES: To describe the impact of treatment on fertility, discuss
      fertility-sparing options available for women with breast cancer, and explore
      pregnancy subsequent to breast cancer. DATA SOURCES: Published research, clinical
      articles, book chapters, and abstracts. DATA SYNTHESIS: The risk of amenorrhea
      associated with alkylating agents in breast cancer survivors is well known.
      Fertility-sparing options before, during, and after treatment are possible with
      the use of assistive reproductive technology. Young breast cancer survivors are
      concerned about stimulating recurrence with subsequent pregnancy, health during
      pregnancy, and family matters. CONCLUSIONS: Current data about the effects of
      treatment on amenorrhea, subsequent pregnancy after treatment, preservation of
      ovarian function during adjuvant therapy, and management of ovarian failure in
      young women with breast cancer are important to include in discussions and
      counseling. IMPLICATIONS FOR NURSING: Young women deserve a thoughtful discussion
      about their concerns among their multidisciplinary team, including oncology
      nurses, oncologists, and social workers. Effects of treatment on fertility are
      well known. Women with fertility concerns should be referred to a reproductive
      endocrinology team at the time of diagnosis rather than after treatment has
      ended.

PMID- 15152275
TI  - "Not lighting up": a case study of a woman who quit smoking.
AB  - PURPOSE/OBJECTIVES: To review the prevalence, incidence, and risks of smoking by
      American women; to outline services, treatments, and educational options for
      smoking prevention and cessation; and to present the conceptual link between the
      epidemiologic and research literature and experiences of one individual in the
      target population--an adult female former smoker with a 30-year habit who began
      smoking during her teenage years. DATA SOURCES: Published literature, expert
      opinion, and an interview with a former smoker--a female healthcare professional
      who had a 30-year habit. DATA SYNTHESIS: Literature was reviewed and the content
      was evaluated for relevance, accuracy, and timeliness. The relevant content was
      augmented with the author's practical experience and applied to the case study to
      make recommendations. CONCLUSIONS: Oncology nurses may use a number of strategies
      to assist people to never start or to stop using tobacco products. The most
      effective strategy begins with collaboration between healthcare professionals and
      patients and a combination of instruction, counseling, and emotional support.
      Oncology nurses can participate in grassroots efforts to educate the public about
      addiction related to tobacco use, provide counseling for patients who smoke, and
      become actively involved in legislative solutions to the problem of tobacco use.
      IMPLICATIONS FOR NURSING: Oncology nurses may intervene to affect positive
      behavioral change and participate in grassroots efforts to educate the public.
      Substantial resources are available to professionals and patients who wish to
      quit smoking or prevent tobacco use by friends and relatives. Nurses should take
      every opportunity to support smoking cessation and tobacco use prevention.

PMID- 15152276
TI  - Development of a measure to delineate the clinical trials nursing role.
AB  - PURPOSE/OBJECTIVES: To identify the significant dimensions of the clinical trials
      nursing role and to construct a reliable and valid survey instrument to reflect
      these dimensions. DESIGN: Methodologic survey. SETTING/SAMPLE: The judge panel
      consisted of six national nurse experts. The focus group sample was comprised of
      24 clinical research nurses from the West, Northeast, and Great Lakes regions of
      the United States and five research nurses from Canada. The sample for instrument
      testing consisted of 40 oncology clinical research nurses from the Southeast.
      METHODS: Several strategies were used to develop the Clinical Trials Nursing
      Questionnaire (CTNQ): literature review, conceptualization of the subscales,
      development of items for each subscale, development of the tool, expert judge
      panel evaluation, focus group testing, administration of the tool, and
      psychometric analysis of the results. MAIN RESEARCH VARIABLES: Frequency and
      importance of clinical trials nursing activities. FINDINGS: Content validity was
      established at 0.95. The alpha reliability coefficient was 0.92 for the frequency
      scale and 0.95 for the importance scale. A two-week test-retest reliability of
      0.88 was obtained for the frequency scale and 0.92 for the importance scale. The
      final CTNQ contained 12 sections with 154 items. CONCLUSIONS: The CTNQ has
      acceptable content validity, internal consistency, and stability reliability.
      This instrument is promising for the assessment of the research nurse role, and
      its use in further research is appropriate. IMPLICATIONS FOR NURSING: A valid and
      reliable measure can be used to delineate the subspecialty of clinical trials
      nursing, thus providing a better understanding of how nursing professionals
      contribute to the cancer research enterprise.

PMID- 15152277
TI  - Teaching ethics in Canadian gastroenterology.

PMID- 15152278
TI  - Helicobacter pylori and the prevention of gastric cancer.
AB  - BACKGROUND: Helicobacter pylori is an important cause of stomach cancer that
      infects a substantial proportion of the Canadian adult population. H pylori can
      be detected by noninvasive tests and effectively eradicated by medical treatment.
      Screening for and treatment of H pylori may represent a significant opportunity
      for preventive oncology. METHODS: Cancer Care Ontario organized a workshop held
      in Toronto, Ontario, on October 24 and 25, 2002, to: review the current state of
      knowledge regarding H pylori treatment and cancer prevention; determine if there
      is currently sufficient evidence to consider the promotion of H pylori treatment
      for the purpose of cancer prevention; identify critical areas for research; and
      advise Cancer Care Ontario on H pylori and cancer prevention. RESULTS: Workshop
      participants developed a number of recommendations for research into the
      relationship between H pylori and stomach cancer, including determining the
      prevalence of infection in different regions of Canada, the pathogenetic sequence
      of carcinogenesis from H pylori infection, and the implementation of a
      prospective observational study. INTERPRETATION: Although the rate of H pylori
      infection is declining in Canada and the treatment of H pylori is generally
      accepted to be safe, the evidence to date may not warrant the implementation of
      population screening for H pylori infection to prevent gastric carcinoma in
      average-risk populations. Rather, a demonstration project is needed to estimate
      prevalence, evaluate the merits of screening, measure patient compliance and
      physician participation, develop education materials, establish a registry for
      monitoring and evaluation, and develop a quality assurance framework.

PMID- 15152279
TI  - Somatostatin versus octreotide in the treatment of patients with gastrointestinal
      and pancreatic fistulas.
AB  - BACKGROUND AND PURPOSE: Gastrointestinal and pancreatic fistulas are
      characterized as serious complications following abdominal surgery, with a
      reported incidence of up to 27% and 46%, respectively. Fistula formation results
      in prolonged hospitalization, increased morbidity/mortality and increased
      treatment costs. Conservative and surgical approaches are both employed in the
      management of these fistulas. The purpose of the present study was to assess,
      evaluate and compare the potential clinical benefit and cost effectiveness of
      pharmacotherapy (somatostatin versus its analogue octreotide) versus conventional
      therapy. PATIENTS AND METHODS: Fifty-one patients with gastrointestinal or
      pancreatic fistulas were randomized to three treatment groups: 19 patients
      received 6000 IU/day of somatostatin intravenously, 17 received 100 microg of
      octreotide three times daily subcutaneously and 15 patients received only
      standard medical treatment. RESULTS: The fistula closure rate was 84% in the
      somatostatin group, 65% in the octreotide group and 27% in the control group.
      These differences were of statistical significance (P=0.007). Overall mortality
      rate was less than 5% and statistically significant differences in mortality
      among the three groups could not be established. Overall, treatment with
      somatostatin and octreotide was more cost effective than conventional therapy
      (control group), and somatostatin was more cost effective than octreotide. The
      average hospital stay was 21.6 days, 27.0 and 31.5 days for the somatostatin,
      octreotide and control groups, respectively. CONCLUSIONS: Data suggest that
      pharmacotherapy reduces the costs involved in fistula management (by reducing
      hospitalization) and also offers increased spontaneous closure rate. Further
      prospective studies focusing on the above parameters are needed to demonstrate
      the clinicoeconomic benefits.

PMID- 15152280
TI  - Serum beta2-microglobulin levels in hepatitis B e antigen-negative chronic
      hepatitis B patients under long term lamivudine monotherapy: relationship with
      virological breakthrough.
AB  - OBJECTIVES: To evaluate the predictive value of serum beta2-microglobulin
      (beta2m) levels for virological breakthrough in hepatitis B e antigen-negative
      chronic hepatitis B patients under long term lamivudine monotherapy. METHODS:
      Serum beta2m levels were calculated at baseline and every three months during
      lamivudine monotherapy in 25 patients with chronic hepatitis B, using
      microparticle enzyme immunoassay technology to investigate their association with
      biochemical, virological and histological outcome data. Cox proportional hazard
      models were used to investigate the association between serum beta2m levels and
      virological breakthrough. RESULTS: Seven of 25 (28%), nine of 25 (36%) and 14 of
      25 (56%) chronic hepatitis B patients exhibited virological breakthrough at
      months 12, 24 and 36 of treatment, respectively. All chronic hepatitis B patients
      who did not show virological breakthrough in the follow-up period exhibited
      beta2m elevation in month 3 of treatment. The duration (in months) of serum
      beta2m elevation was significantly higher in the responders group than the
      nonresponders group (7.3 +/- 2.6 versus 3.8 +/- 3.4, P=0.02). In contrast to
      patients whose serum beta2m levels were increased at three months, patients whose
      beta2m levels were decreased had a 4.6 times higher risk of experiencing
      virological breakthrough (hazards ratio 4.6, 95% CI 1.22 to 17.36). When age,
      pretreatment serum alanine aminotransferase and hepatitis B virus DNA levels, and
      grade of liver disease were simultaneously included in the same Cox model,
      decreased beta2m status was still associated with increased risk of virological
      breakthrough (hazards ratio 12.2, 95% CI 1.28 to 116.8). CONCLUSIONS: In
      hepatitis B e antigen-negative chronic hepatitis B patients under long term
      lamivudine monotherapy, serum b2m levels at three months of treatment, compared
      with baseline levels, are good predictors of risk for virological breakthrough.

PMID- 15152281
TI  - Ethical issues in Canadian gastroenterology: results of a survey of Canadian
      gastroenterology trainees.
AB  - BACKGROUND: Specialty-specific bioethical education is a mandated component of
      gastroenterology training programs in Canada, but no gastroenterology-specific
      bioethical curriculum is available. PURPOSE: To assess the relative importance of
      a variety of bioethical issues to the practice of gastroenterology. METHOD: A
      convenience sample of Canadian gastroenterology residents and staff was surveyed
      at a national meeting for Canadian gastroenterology trainees. They were asked to
      indicate their opinions of the relative importance of 24 different bioethical
      issues in their practice of gastroenterology. RESULTS: Respondents made
      distinctions in the relevance of different bioethical issues to the practice of
      gastroenterology and there was substantial concordance in the rankings indicated
      by residents and staff. Truth telling, consent and the capacity to give consent,
      and consent with regard to specific endoscopic procedures were ranked by both
      residents and staff as most important to their practice of gastroenterology. In
      contrast, the issue of euthanasia and assisted suicide was ranked near the bottom
      of the list by both residents and staff. The results differ in some respects from
      the key ethical questions identified by opinion leaders in gastroenterology.
      INTERPRETATION: Gastroenterology residents and staff identify some topics as much
      more relevant than others to the practice of gastroenterology. It is proposed
      that this can provide a framework for developing a gastroenterology-specific
      bioethical curriculum, and that there is an important opportunity for developing
      a joint program through collaboration among gastroenterology training programs
      across Canada.

PMID- 15152282
TI  - Advanced colon cancer before the age of 20 years: a case for extension of the
      current colonoscopy surveillance guidelines in hereditary nonpolyposis colorectal
      cancer syndrome.
AB  - BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) currently accounts
      for between 2% to 6% of all colorectal adenocarcinomas. Controversies exist
      regarding the current guidelines for colonoscopic screening for colon cancer.
      CASE REPORT: A case of colon cancer in a young Japanese man with a family history
      of colon cancer that did not meet the criteria for HNPCC is reported. A malignant
      pelvic mass discovered shortly before his 20th birthday prompted a colonoscopy.
      The findings at colonoscopy determined that the patient and his family fulfilled
      the criteria of HNPCC. CONCLUSION: Before finding a pelvic mass metastatic from
      adenocarcinoma of the ascending colon, this patient was clearly outside of the
      current guidelines for HNPCC screening. It is suggested that in similar patients,
      even if they do not fulfill all the criteria for HNPCC, it would be appropriate
      to consider screening well before the recommended lower age.

PMID- 15152283
TI  - Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients
      refractory to standard therapy.
AB  - There are limited therapeutic options available for patients with autoimmune
      hepatitis in whom conventional treatment fails. A case series of five patients
      unresponsive to or unable to take azathioprine, 6-mercaptopurine or
      corticosteroids who were treated with mycophenolate mofetil (MMF) is reported.
      While on MMF, alanine aminotransferase normalized or remained normal in all
      patients. MMF had a steroid-sparing effect and histological remission was
      demonstrated in one patient after seven months of MMF. One patient experienced an
      uncomplicated episode of pyelonephritis. In conclusion, MMF can effectively
      induce and maintain remission in refractory autoimmune hepatitis patients.

PMID- 15152284
TI  - Synchronous collagenous sprue and enteropathy-type T cell lymphoma: variants of
      the same disease.
AB  - A 64-year-old man with treated hypothyroidism had 10 months of diarrhea,
      abdominal pain, anorexia and recent involuntary 13.6 kg weight loss. He presented
      to hospital with an acute abdomen that had a radiological correlate of free air
      under the diaphragm. He was diagnosed with a perforated mid-jejunum due to an
      ulcerated enteropathy-type T cell lymphoma (ETL), complicating collagenous sprue
      and cryptic celiac disease. Polymerase chain reaction verified monoclonal gamma-
      and beta-T cell receptor gene rearrangements in the neoplasm. He had a complete
      resolution of symptoms when treated with a gluten-free diet in the postoperative
      period. This is apparently the first report describing collagenous sprue and ETL
      as synchronous lesions. Because atypical CD8+ lymphocytes are in both the
      collagenous sprue epithelium and ETL, the implication is that collagenous sprue
      is a noninvasive component of the ETL.

PMID- 15152285
TI  - Complete histological resolution of collagenous sprue.
AB  - A 65-year-old woman developed a watery diarrhea syndrome with collagenous
      colitis. Later, weight loss and hypoalbuminemia were documented. This prompted
      small bowel biopsies that showed pathological changes of collagenous sprue. An
      apparent treatment response to a gluten-free diet and prednisone resulted in
      reduced diarrhea, weight gain and normalization of serum albumin. Later repeated
      biopsies from multiple small and large bowel sites over a period of over three
      years, however, showed reversion to normal small intestinal mucosa but persistent
      collagenous colitis. These results indicate that collagenous inflammatory disease
      may be a far more extensive process in the gastrointestinal tract than is
      currently appreciated. Moreover, collagenous colitis may be a clinical signal
      that occult small intestinal disease is present. Finally, collagenous sprue may,
      in some instances, be a completely reversible small intestinal disorder.

PMID- 15152286
TI  - cagA-seropositive strains of Helicobacter pylori increase the risk for gastric
      cancer more than the presence of H pylori alone.

PMID- 15152287
TI  - CAG Research Committee Report: another stellar year for Canadian gastrointestinal
      research.

PMID- 15152288
TI  - Postmortem of the postmortem.

PMID- 15152289
TI  - Regional outcomes of heart failure in Canada.
AB  - BACKGROUND: Heart failure is a condition associated with significant mortality
      and morbidity. However, demographic features and outcomes following
      hospitalization for heart failure, and associated regional comparisons have not
      been performed in Canada. METHODS: Anonymously rendered records of patients
      hospitalized for incident heart failure in Canada were selected from the Canadian
      Institute for Health Information discharge abstract and hospital morbidity
      databases from fiscal years 1997/1998 to 1999/2000. The demographics, in-hospital
      mortality rate and heart failure readmission rates were compared among provinces
      and health regions. RESULTS: A total of 83,406 patients were hospitalized for
      heart failure across Canada during the study period. The number of cases
      increased dramatically with each decade after age 50 years, with 85% of
      hospitalized patients being age 65 years and over. On average, in-hospital
      mortality per index admission in Canada was 9.5 deaths per 100 hospitalized
      cases. While the greatest burden of readmissions was among those 65 years of age
      and over, heart failure readmission rates were similar across age groups. Among
      all patients surviving the index admission, heart failure readmission rates were
      8.7%, 14.1% and 23.6% at 30 days, 90 days and one year, respectively. The highest
      age- and sex-adjusted in-hospital mortality rates were 11.9% (95% CI 10.6 to
      13.2) in Newfoundland/Labrador and 11.6% (95% CI 10.6 to 12.7) in Nova Scotia.
      The highest readmission rates at one year were 26.9% (95% CI 24.9 to 28.9) in
      Newfoundland/Labrador, 26.3% (95% CI 25.0 to 27.7) in Saskatchewan and 25.2% (95%
      CI 24.3 to 26.1) in British Columbia. There were significant regional variations
      in heart failure readmission rates and mortality. CONCLUSIONS: There is a great
      burden of heart failure in Canada, increasing significantly with age. The
      mortality and readmission rates for this condition are high and exhibit variation
      among health regions and provinces. Factors contributing to regional variations
      in these outcomes merit further study.

PMID- 15152290
TI  - Six-month outcomes after single- and multi-lesion percutaneous coronary
      intervention: results from the ROSETTA registry.
AB  - BACKGROUND: The American College of Cardiology/American Heart Association
      exercise testing guidelines suggest that routine functional testing may benefit
      patients at high risk of restenosis, such as those undergoing multi-lesion
      percutaneous coronary intervention (PCI). OBJECTIVES: To compare the six-month
      post-PCI clinical and procedural outcomes in patients following single- and multi
      lesion PCI, and to examine the use of routine functional testing (ie, in all
      patients) versus selective functional testing (ie, only in those with recurrent
      symptoms) following multi-lesion PCI. METHODS: Six-month outcomes among 562
      patients after single-lesion PCI and 229 patients after multi-lesion PCI were
      examined. All patients were enrolled in the Routine versus Selective Exercise
      Treadmill Testing after Angioplasty (ROSETTA) registry, a prospective,
      multicentre registry examining the use of functional testing after successful
      PCI. RESULTS: For single- versus multi-lesion PCI patients, respectively, rates
      of death (1.8% versus 2.2%, P=0.7) and myocardial infarction (0.7% versus 2.6%,
      P=0.03) were low in both groups. Rates of unstable angina (12.0% versus 11.7%,
      P=0.9) and the composite clinical end point of death, myocardial infarction or
      unstable angina (13.5% versus 13.9%, P=0.9) were similar. Multi-lesion PCI
      patients had a higher number of repeat PCI procedures (6.6% versus 13.4%, P=0.02)
      but there was no difference in the rates of coronary artery bypass graft surgery
      (3.0% versus 2.6%, P=0.7). A routine functional testing strategy was used in
      28.0% of single-lesion and 31.6% of multi-lesion patients. In a multivariate
      analysis of the multi-lesion patients, routine functional testing was not
      associated with a significant reduction in the composite clinical event rate
      (odds ratio 0.5, 95% CI 0.2 to 1.7, P=0.27). CONCLUSIONS: During the six-month
      period following successful PCI, clinical event rates were similar among patients
      undergoing single- or multi-lesion PCI. Routine functional testing was not
      associated with a statistically significant benefit in patients after multi
      lesion PCI. However, additional study is required to better define the role of
      routine functional testing in this subgroup of patients.

PMID- 15152292
TI  - Continuous renal replacement therapy after heart transplantation.
AB  - BACKGROUND: Renal failure following heart transplantation carries a poor
      prognosis. The objectives of this study were to determine risk factors for renal
      failure requiring continuous renal replacement therapy (CRRT), to describe the
      management strategies regarding immunosuppressive therapy and to examine the
      short-term prognosis. METHODS: Fifty-six patients who underwent heart
      transplantation from 1998 to 2002 at the Montreal Heart Institute were
      retrospectively analyzed. RESULTS: Six of 56 patients (11%) underwent CRRT after
      heart transplantation. Patients who underwent CRRT had lower preoperative
      creatinine clearance than those who did not (median 44 versus 59 mL/min, P=0.04)
      and lower first two-week postoperative creatinine clearance (median 23 versus 42
      mL/min, P<0.01) compared with patients without CRRT. The total duration of CRRT
      ranged between two and 60 days (median 15 days). Cyclosporine was withheld for 12
      days versus two days (P<0.01) and the time to achieve therapeutic levels of
      cyclosporine averaged 18 days versus nine days (P=0.01) among CRRT versus non
      CRRT patients. Patients were administered thymoglobulin or basiliximab during
      cyclosporine withholding. The time to discharge from hospital after
      transplantation was longer in patients with CRRT (median 47 days versus 17 days,
      P<0.01). There was no mortality at three months in the CRRT group. CONCLUSION:
      Creatinine clearance is an important predictor of renal failure requiring renal
      replacement therapy. Although renal failure remains a serious complication after
      transplantation, the use of CRRT and antilymphocyte agents during cyclosporine A
      withholding is associated with a favourable short-term prognosis following heart
      transplantation.

PMID- 15152291
TI  - Losartan reduces the costs associated with nephropathy and end-stage renal
      disease from type 2 diabetes: Economic evaluation of the RENAAL study from a
      Canadian perspective.
AB  - BACKGROUND: The Reduction of Endpoints in NIDDM [non-insulin-dependent diabetes
      mellitus] with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated
      the renoprotective effects of losartan in patients with nephropathy from type 2
      diabetes. OBJECTIVE: To perform an economic evaluation of the costs associated
      with end-stage renal disease (ESRD) from a Canadian public health perspective,
      based on the clinical outcomes reported in the RENAAL study. METHODS: ESRD
      related costs were determined by estimating the mean number of days with ESRD
      multiplied by the daily cost of ESRD (140 dollars); mean days with ESRD were
      calculated by subtracting the area under the Kaplan-Meier survival curve for time
      to the first event of ESRD or all-cause mortality from the area under the curve
      for all-cause mortality. Daily ESRD cost was determined using Canadian specific
      data sources. ESRD-related cost savings with losartan were obtained by
      subtracting the ESRD-related costs of the losartan group from those of the
      placebo group. Net cost savings were ESRD-related cost savings with losartan
      minus the drug cost of losartan. RESULTS: Losartan reduced the number of ESRD
      days by 33.6 per patient over 3.5 years (95% CI 10.9 to 56.3) compared with
      placebo. Losartan reduced ESRD-related costs by 4,695 dollars per randomized
      patient over 3.5 years (95% CI 1,523 dollars to 7,868 dollars). After accounting
      for the drug cost of losartan, net cost savings with losartan were 3,675 dollars
      per randomized patient over 3.5 years. CONCLUSION: Losartan therapy for patients
      with nephropathy from type 2 diabetes reduces the clinical incidence of ESRD and
      can result in considerable cost savings for the Canadian public health system.

PMID- 15152293
TI  - Intravenous nicorandil can reduce the occurrence of ventricular fibrillation and
      QT dispersion in patients with successful coronary angioplasty in acute
      myocardial infarction.
AB  - BACKGROUND: Because nicorandil, a potassium channel opener, has a
      cardioprotective effect and attenuates reperfusion injury in patients with acute
      myocardial infarction (AMI), intravenous nicorandil should reduce arrhythmic
      mortality and QT dispersion in patients with AMI. OBJECTIVES: The purpose of this
      study was to evaluate whether intravenous nicorandil reduces the occurrence of
      ventricular fibrillation and QT dispersion in patients with successful coronary
      angioplasty in AMI. METHODS: A historical cohort study on the effect of
      nicorandil on ventricular fibrillation and QT dispersion was conducted. Eighty
      three patients with AMI who underwent successful percutaneous transluminal
      coronary angioplasty (PTCA) were enrolled. The patients were divided into two
      groups: nicorandil (n=46) and control group (n=37). Nicorandil was injected at 4
      mg/h continuously from admission to 48 h after PTCA in the nicorandil group. QT
      dispersion was measured before, immediately after, 24 h after and 48 h after
      PTCA. RESULTS: Ventricular fibrillation was observed in three patients in the
      control group, but none was observed in the nicorandil group. QT dispersion in
      the nicorandil group was shorter than that in the control group 48 h after PTCA
      (QT dispersion was 23.2+/-16.1 ms and 33.4+/-24.0 ms, respectively, P<0.05).
      There was a significant difference between the two groups in time course after
      the onset of AMI (P<0.05). CONCLUSIONS: Because intravenous nicorandil reduces
      the occurrence of ventricular fibrillation and QT dispersion in patients with
      successful coronary angioplasty in AMI, it would prevent the occurrence of
      cardiac events after successful PTCA for AMI.

PMID- 15152296
TI  - Issues influencing development of the Canadian Cardiovascular Information
      Network.
AB  - The 1995 Consensus Conference of the Canadian Cardiovascular Society on
      "Indications for and Access to Revascularization" recommended that Canadian
      centres with invasive cardiovascular facilities should participate in a national
      observational database that monitors the selection of patients, as well as
      evaluate outcomes. The Canadian Cardiovascular Society, the Heart and Stroke
      Foundation of Canada, and Health Canada with IBM as a partner, initiated a
      process to identify factors influencing the development of the Canadian
      Cardiovascular Information Network. IBM's "Business Discovery Methodology" was
      adapted for health care. Structured interviews with representatives of health
      organizations, cardiovascular databases and research institutes were conducted
      across Canada, followed by a workshop to identify goals, issues and challenges.
      Participants identified goals for a cardiovascular database (eg, evidence-based
      decision-making), project related issues (eg, respecting the integrity of
      existing databases) and health care related issues (eg, cardiac waiting lists).
      Challenges included initial mistrust between representatives of provincial
      cardiovascular databases and national agencies, and a lack of sustained funding.
      A Project Team was formed to address 'cardiac waiting lists'. Analysis of Alberta
      and Ontario data identified differences in definitions, such as when the waiting
      time for bypass surgery began, that impeded detailed comparisons. Development of
      a centralized national database was not feasible at this time for political,
      technical and financial reasons. However, provincial cardiovascular database
      representatives agreed to work together and to share aggregate data and analyses.
      A first step toward developing a national surveillance system for cardiovascular
      services will be achieving consensus about standardizing data definitions. This
      process will require sustained funding.

PMID- 15152295
TI  - Atherosclerotic plaque inflammation: the final frontier?

PMID- 15152297
TI  - Surgical treatment of infective endocarditis complicated by intracranial
      hemorrhage in a patient with hypertrophic obstructive cardiomyopathy.
AB  - A patient with hypertrophic obstructive cardiomyopathy developed mitral
      regurgitation due to infective endocarditis. The patient, a 29-year-old man with
      a 16-year history of a severe obstructive form of hypertrophic obstructive
      cardiomyopathy (left ventricular outflow gradient more than 100 mmHg), was
      admitted with bacteremia. During medical therapy with antibiotics for six months,
      the patient suffered an intracranial hemorrhage without a mycotic aneurysm and
      developed severe mitral regurgitation due to the infective endocarditis. One
      month after clinical stability of the cerebral damage, the patient underwent a
      combined mitral valve replacement and transaortic septal myectomy. Postoperative
      echocardiography revealed that the left ventricular outflow gradient had
      decreased to 15 mmHg. Ten months after the combined operation, the patient was
      well and asymptomatic.

PMID- 15152298
TI  - Single coronary artery--a rarity in the catheterization laboratory: case report
      and current review.
AB  - A single coronary artery is a rare anomaly but has been associated with sudden
      cardiac death. A 73-year-old man with atypical chest pain and exercise-induced
      ischemia arising from a single coronary artery with the left main coronary stem
      originating from the proximal right coronary artery and passing posterior and
      inferior to the aortic root is described. The exact three-dimensional course was
      not reliably established by coronary angiography but was clearly demonstrated by
      contrast-enhanced electron beam tomography. The most reasonable hypotheses for
      myocardial ischemia and sudden death emphasize the accentuation of the angle at
      the origin of specific distribution patterns of an anomalous coronary artery that
      may compromise coronary blood flow. Other mechanisms such as coronary spasm and
      hypoplasia are also discussed. The literature review provides a historic overview
      and insights into the developmental history of the anomaly, classification of the
      various morphological patterns, clinical significance and therapeutic approaches.

PMID- 15152301
TI  - Safe as houses? Indoor air pollution and health.
AB  - Indoor air pollution has long been the Cinderella of the environmental world:
      left at home, out of sight and out of mind. But as our knowledge of indoor
      pollution grows, policy-makers are coming to realise that improving indoor
      environments can deliver big gains for public health. The new front line on air
      quality will be on our own doorsteps.

PMID- 15152303
TI  - Research profile. Max Costa.

PMID- 15152304
TI  - Second International Conference on Environmental, Health and Safety Aspects
      Related to the Production of Aluminium (EHSARPA), 26 September-1 October 2003,
      St. Petersburg, Russia.

PMID- 15152305
TI  - Guidelines for biological monitoring of workers in aluminium production
      facilities for urinary 1-hydroxypyrene (1-pyrenol).

PMID- 15152306
TI  - The biological behaviour and bioavailability of aluminium in man, with special
      reference to studies employing aluminium-26 as a tracer: review and study update.
AB  - Until 1990 biokinetic studies of aluminium metabolism and biokinetics in man and
      other animals had been substantially inhibited by analytical and practical
      difficulties. Of these, the most important are the difficulties in
      differentiating between administered aluminium and endogenous aluminium
      especially in body fluids and excreta and the problems associated with the
      contamination of samples with environmental aluminium. As a consequence of these
      it was not possible to detect small, residual body burdens of the metal following
      experimental administrations. Consequently, many believed aluminium to be
      quantitatively excreted within a short time of uptake in all, but renal-failure
      patients. Nevertheless, residual aluminium deposits in a number of different
      organs and tissues had been detected in normal subjects using a variety of
      techniques, including histochemical staining methods. In order to understand the
      origins and kinetics of such residual aluminium deposits new approaches were
      required. One approach taken was to employ the radioisotope (67)Ga as a
      surrogate, but this approach has been shown to be flawed-a consequence of the
      different biological behaviours of aluminium and gallium. A second arose from the
      availability, in about 1990, of both (26)Al-a rare and expensive isotope of
      aluminium-and accelerator mass spectrometry for the ultra-trace detection of this
      isotope. Using these techniques the basic features of aluminium biokinetics and
      bioavailability have been unravelled. It is now clear that some aluminium is
      retained in the body-most probably within the skeleton, and that some deposits in
      the brain. However, most aluminium that enters the blood is excreted in urine
      within a few days or weeks and the gastrointestinal tract provides an effective
      barrier to aluminium uptake. Aspects of the biokinetics and bioavailability of
      aluminium are described below.

PMID- 15152307
TI  - Assessing workplace chemical exposures: the role of exposure monitoring.
AB  - Occupational exposure is the condition of being subjected through employment to a
      chemical, physical, or biological agent, or to a specific process, practice,
      behavior, or organization of work. Exposure to a chemical agent is typically the
      contact of that agent with the outer boundary of a subject, such as the
      respiratory system, skin, or digestive system. In occupational hygiene we are
      most concerned with exposure through the respiratory system, although,
      increasingly we are concerned with the results of dermal exposures, including
      those exposures to the skin that can be transferred to the mouth and digestive
      system. This presentation will detail methods available for assessing personal
      exposures to chemicals through monitoring. The results from monitoring can then
      be compared to established guidelines and regulations, although this is not the
      only rationale for making measurements. These monitoring methods are currently
      used around the world to establish the benchmark hazard from which risk to the
      worker can be predicted. The presentation will describe the general techniques
      for assessing exposures to the respiratory system from chemical gases and vapors,
      chemical dusts, and exposures to the skin from bulk chemicals or chemical
      contamination of surfaces. For respiratory exposures, direct-reading instruments
      are available for spot measurements, and for monitoring short-term fluctuations
      in concentration. However, most standards and regulations are based on time
      integrated (time-weighted average) exposures, requiring longer-term integrative
      methods. Therefore, the specific focus of this review will be the methods
      available for full work-shift sampling. For gases and vapors this will include
      taking whole-air samples in canisters or polymer bags, or concentration of
      chemicals by absorption in liquids or adsorption on solid sorbents, with
      subsequent chemical analysis. Chemical concentration can take place by pumping
      air through the sorbing media, or by allowing molecules to diffuse to the sorbent
      surface. Transfer of the collected chemicals to the analytical instrumentation
      can be accomplished using solvent displacement and injection, or through the
      application of heat to bring the collected molecules back into the vapor phase.
      For particles, the particle size is important as this determines the site of
      deposition in the lungs, and so time-integrated sampling on filters using various
      types of size-selective samplers is preferred. Finally, some techniques that have
      been used to assess the potential for chemical contamination of the skin are
      presented. Biomonitoring is another tool that can be used to assess exposure, and
      the results are more relevant to dosimetric considerations than exposure.
      Biomonitoring is a complex subject worthy of a separate review, and will be
      considered only briefly here.

PMID- 15152308
TI  - Naphthalene and its biomarkers as measures of occupational exposure to polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAH) include compounds with two or more fused
      benzene rings, many of which are carcinogens. Industrial sources produce hundreds
      of PAH, notably in the coke- and aluminium-producing industries. Because PAH are
      distributed at varying levels between gaseous and particulate phases, exposure
      assessment has been problematic. Here, we recommend that occupational exposures
      to naphthalene be considered as a potential surrogate for occupational PAH
      exposure for three reasons. Naphthalene is usually the most abundant PAH in a
      given workplace; naphthalene is present almost entirely in the gaseous phase and
      is, therefore, easily measured; and naphthalene offers several useful biomarkers,
      including the urinary metabolites 1- and 2-hydroxynaphthalene. These biomarkers
      can be used to evaluate total-body exposure to PAH, in much the same way that 1
      hydroxypyrene has been applied. Using data from published sources, we show that
      log-transformed airborne levels of naphthalene are highly correlated with those
      of total PAH (minus naphthalene) in several industries (creosote impregnation:
      Pearson r= 0.815, coke production: r= 0.917, iron foundry: r= 0.854, aluminium
      production: r= 0.933). Furthermore, the slopes of the log-log regressions are
      close to one indicating that naphthalene levels are proportional to those of
      total PAH in those industries. We also demonstrate that log-transformed urinary
      levels of the hydroxynaphthalenes are highly correlated with those of 1
      hydroxypyrene among coke oven workers and controls (r= 0.857 and 0.876), again
      with slopes of log-log regressions close to one. These results support the
      conjecture that naphthalene is a useful metric for occupational PAH exposure.
      Since naphthalene has also been shown to be a respiratory carcinogen in several
      animal studies, it is also argued that naphthalene exposures should be monitored
      per se in industries with high levels of PAH.

PMID- 15152309
TI  - Archives of environmental contamination.

PMID- 15152310
TI  - Natural and anthropogenic enrichments of molybdenum, thorium, and uranium in a
      complete peat bog profile, Jura Mountains, Switzerland.
AB  - A core from an ombrotrophic Swiss bog representing 12 370 (14)C years of peat
      accumulation was evaluated as a possible archive of atmospheric deposition of Mo,
      Th and U. Calcium, Sr, and Ba were also determined to quantify weathering inputs,
      Mn to follow possible redox transformations, and Rb to identify plant uptake.
      Each of these elements was determined using ICP-MS, following digestion in a
      microwave heated autoclave using 3 ml HNO(3) and 0.1 ml HBF(4). Calcium and Sr
      clearly identify the thickness of the ombrotrophic zone because they are enriched
      in the minerogenic zone relative to the concentration of mineral matter. The
      concentration of Ba, however, is proportional to the concentration of mineral
      matter in all samples, and is not added to peat column by weathering reactions at
      the peat-sediment interface. The lowest element concentrations are found during
      the Holocene climate optimum (5320 to 8030 (14)C year BP) with the following
      natural background values (n= 18): Mo 0.08 +/- 0.02 microg g(-1), U 0.029 +/-
      0.008 microg g(-1), Ba 5.2 +/- 2.6 microg g(-1), Th 0.070 +/- 0.022 microg g(-1)
      and Rb 0.63 +/- 0.09 microg g(-1). By far the highest concentrations of Ba, Mn,
      Rb and Th were found during the Younger Dryas cold climate event (10 590 (14)C
      year BP) when the flux of atmospheric soil dust was at its post-glacial maximum.
      Molybdenum and U are elevated in concentration throughout the minerogenic zone
      because of sediment weathering and this masks the atmospheric signal in samples
      older than ca. 8000 (14)C year BP (ca. 9000 calendar years). Enrichment factors
      (EF) calculated using Sc as a conservative, lithogenic element shows that
      minerogenic peats are enriched in Mo up to 18x and U 26x, relative to the natural
      "background" values. During the two millennia prior to industrialisation, the
      accumulation rate of atmospheric Mo averaged 0.23 +/- 0.13 microg m(-2) year(-1).
      With the onset of the Industrial Revolution, Mo accumulation rates rapidly and
      continuously increased to approximately 10 microg m(-2) year(-1) in the late
      1980s. These data suggest that Mo in atmospheric aerosols today is derived
      predominately from anthropogenic emissions. Uranium does not show the same
      enrichment pattern which suggests that steel-making rather than coal combustion
      is the primary source of atmospheric Mo contamination at this site.

PMID- 15152311
TI  - Atmospheric deposition of silver and thallium since 12 370 14C years BP recorded
      by a Swiss peat bog profile, and comparison with lead and cadmium.
AB  - A peat core from an ombrotrophic bog in Switzerland provides the first complete,
      long-term record (14 500 years) of atmospheric Ag and Tl deposition. The lack of
      enrichment of Ag and Tl in the basal peat layer shows that mineral dissolution in
      the underlying sediments has not contributed measurably to the Ag and Tl
      inventories in the peat column, and that Ag and Tl were supplied exclusively by
      atmospheric deposition. The temporal and spatial distribution of modern peaks in
      Ag and Tl concentrations are similar to those of Pb which is known to be immobile
      in peat profiles. Silver and Tl, therefore, are effectively immobile in the peat
      bog also, allowing an atmospheric deposition chronology to be reconstructed.
      Silver concentrations vary by up to 114x and Tl up to 241x. While Holocene
      climate change and land use history can explain the variation in metal
      concentrations and enrichment factors (EF) in ancient peats (i.e. pre-dating the
      Roman Period), anthropogenic sources have to be invoked to explain the very high
      EF values (up to 123 in the case of Ag and 12 in the case of Tl) in peat samples
      since the middle of the 19th Century. The "natural background" EF of Tl in
      ancient peats is remarkably close to unity, indicating a lack of significant
      enrichment of this element in atmospheric aerosols due to chemical weathering of
      crustal rocks. Silver, on the other hand, shows a pronounced enrichment from 8030
      to 5230 (14)C years BP (12x compared to crustal rocks); this may be due to
      weathering phenomena or biological processes, both of which are driven by
      climate. Even compared to the natural enrichment of Ag during the mid-Holocene,
      however, the enrichments of Ag and Tl in modern peats from the Industrial Period
      are at least an order of magnitude greater. The Pb/Ag and Tl/Ag ratios show that
      Pb and Tl are preferentially released, compared to Ag, during smelting of
      argentiferous Pb ores mined during the Roman and Medieval Periods.

PMID- 15152312
TI  - Secondary mobilisation of heavy metals in overbank sediments.
AB  - Heavy metal mobility was studied in overbank sediments of the Grote Beek river in
      Central Belgium. The geochemical signature of heavy metals in fine-scale sampled
      overbank sediments was compared with data on heavy metal emission into the river.
      The influence of acidification, organic and inorganic complexation on heavy metal
      mobility in overbank sediments was studied by single and sequential extractions
      and leaching tests. As confirmed by these tests, the elevated CaCl(2) content of
      the river water significantly enhanced the mobilisation of especially Cd, while
      Zn was mobilised to a lesser extent. The mobilisation of As on the other hand
      decreased in the presence of elevated CaCl(2) concentrations. Based on the
      results of single extractions, two highly contaminated zones with a different Cd
      mobility were observed in one of the overbank profiles. A detailed investigation
      of Cd leaching behaviour in the zone of Fe-accumulation during pH(stat) leaching
      tests, suggested that it was related to the association of Cd with Fe-oxides,
      while adsorption was the dominant binding form of Cd in the clay-rich part of the
      overbank sediment profile.

PMID- 15152313
TI  - 14C and delta13C characteristics of organic matter and carbonate in saltmarsh
      sediments from south west Scotland.
AB  - The distribution of contaminant radionuclides from the Sellafield nuclear fuel
      reprocessing plant was used to establish chronologies for three saltmarsh
      sediment cores from south west Scotland. delta(13)C and (14)C analyses indicated
      that the cores provided a useful archive record of variations in input of organic
      matter and carbonate. The results imply that prior to major releases of
      contaminant (14)C from Sellafield, the (14)C specific activity of organic matter
      in Irish Sea offshore sediments was about 24 Bq kg(-1) C, while that of the
      carbonate component was below the limit of detection. These results provide
      baseline data for modelling the uptake of contaminant (14)C by the Irish Sea
      sediment system. The study confirmed that small(13)C analyses provide a sensitive
      means of apportioning the origin of saltmarsh organic matter between C(3)
      terrigenous plants, C(4) terrigenous plants and suspended particulate marine
      organic matter. For the <2 mm fraction of sediment, a clear pattern of decreasing
      marine organic input was observed in response to increasing elevation of the
      marsh surface as a result of sediment accumulation. Bulk sediment, including
      detrital vegetation, had a dominant input from terrigenous plants. The combined
      use of delta(13)C and (14)C data revealed that organic matter in the marine
      organic component of the <2 mm fraction of contemporary surface sediments of the
      saltmarshes is dominated by recycled old organic material.

PMID- 15152314
TI  - A 300 year history of lead contamination in northern French Alps reconstructed
      from distant lake sediment records.
AB  - Lead concentrations and isotopic ratios were measured along two well-dated
      sediment cores from two distant lakes: Anterne (2100 m a.s.l.) and Le Bourget
      (270 m a.s.l.), submitted to low and high direct human impact and covering the
      last 250 and 600 years, respectively. The measurement of lead in old sediment
      samples (>3000 BP) permits, in using mixing-models, the determination of lead
      concentration, flux and isotopic composition of purely anthropogenic origin. We
      thus show that since ca. 1800 AD the regional increase in lead contamination was
      mostly driven by coal consumption ((206)Pb/(207)Pb approximately 1.17-1.19;
      (206)Pb/(204)Pb approximately 18.3-18.6), which peaks around 1915 AD. The
      increasing usage of leaded gasoline, introduced in the 1920s, was recorded in
      both lakes by increasing Pb concentrations and decreasing Pb isotope ratios. A
      peak around 1970 ((206)Pb/(207)Pb approximately 1.13-1.16; (206)Pb/(204)Pb
      approximately 17.6-18.0) corresponds to the worldwide recorded leaded gasoline
      maximum of consumption. The 1973 oil crisis is characterised by a drastic drop of
      lead fluxes in both lakes (from approximately 35 to <20 mg cm(-2) yr(-1)). In the
      late 1980s, environmental policies made the Lake Anterne flux drop to pre-1900
      values (<10 mg cm(-2) yr(-1)) while Lake Le Bourget is always submitted to an
      important flux (approximately 25 mg cm(-2) yr(-1)). The good match of our distant
      records, together and with a previously established series in an ice core from
      Mont Blanc, provides confidence in the use of sediments as archives of lead
      contamination. The integration of the Mont Blanc ice core results from Rosman et
      al. with our data highlights, from 1990 onward, a decoupling in lead sources
      between the high elevation sites (Lake Anterne and Mont Blanc ice core),
      submitted to a mixture of long-distance and regional contamination and the low
      elevation site (Lake Le Bourget), where regional contamination is predominant.

PMID- 15152315
TI  - Paleolimnological assessment of Grove and Plow Shop Ponds, Ayer, Massachusetts,
      USA--a superfund site.
AB  - Three sediment cores from each of severely polluted Grove and Plow Shop Ponds,
      Ayer, Massachusetts, USA, were dated using (210)Pb, characterized for plant
      macrofossil assemblages, and analyzed for H(2)O, loss-on-ignition, stable Pb
      isotopes, and concentrations of As, Ca, Cd, Cr, Cu, Fe, Hg, methyl-Hg, Ni, Pb,
      and Zn. A core from nearby kettle Spectacle Pond, Littleton, Massachusetts, was
      similarly characterized (except for plant macrofossil assemblages) to assess the
      regional air pollution signal in sediment for comparison with the six cores.
      Accumulation rates for metals (mass per area per year), the anthropogenic
      component (mass per area per year), and total accumulation of the anthropogenic
      component (mass per area) indicate that As, Cd, Cr, Cu, Hg, methyl-Hg, Ni, Pb,
      and Zn have accumulated in sediment as a consequence of point source pollution
      from within the drainage basins of Grove and Plow Shop Ponds. Three distinct
      sources of pollution are inferred. As is entering Plow Shop Pond via groundwater
      in the southwest. Cd, Ni, Pb, and Zn are entering the system predominantly at the
      eastern end of, or upstream from, Grove Pond. Pb also comes from the northwest
      corner of Grove Pond, the principal source of Cr, Cu, and Hg. These results are
      consistent with chemistry of modern surface sediments. The history of pollution
      extends back more than 100 years. Intra- and inter-core variability of
      concentrations and accumulation rates indicate that much of the pollution was
      likely in particulate form with little physical redistribution. Recently,
      concentrations and accumulation rates have generally decreased substantially for
      those elements present in excessive concentrations in the past. This is a
      consequence of accumulation of recent, less polluted sediment. In Spectacle Pond,
      the nearby reference lake, accumulation rates for As, Cd, Hg, and Pb, adjusted
      for background values and changes in sedimentation rate, increased above
      background starting in the late 19th century, peaked about 1980, and declined
      substantially to 2000. These decreases suggest that the anthropogenic (pollution)
      component of atmospheric deposition of these elements declined after 1980 by at
      least 50%(As), 80%(Cd), 80%(Hg), and 80%(Pb).

PMID- 15152316
TI  - Natural mercury enrichment in a minerogenic fen--evaluation of sources and
      processes.
AB  - Mercury (Hg) records in natural archives such as peat bogs are often used to
      evaluate anthropogenic or climatic influences on atmospheric Hg deposition. In
      this context, there is an ongoing discussion about natural sources or processes
      of Hg enrichment in natural archives. In the present study we estimated Hg fluxes
      from rock weathering, direct atmospheric deposition and from indirect atmospheric
      deposition in the catchment of a pristine minerogenic fen (GC2) located in the
      Magellanic Moorlands, southernmost Chile. The Hg record in the bog covers 11 174
      cal. (14)C years and shows Hg concentrations of up to 570 [micro sign]g kg(-1)
      with an average of 268 [micro sign]g kg(-1). Hg was found to be enriched in the
      peat by a factor of 81 if compared to the mean Hg concentrations in the rocks of
      the catchment (3.2 [micro sign]g kg(-1)). Hg and also Pb, Fe, and As were found
      to be enriched predominately in goethite layers indicating high retention of
      these elements in the bog by iron oxyhydrates. It could also be demonstrated that
      the high peat decomposition rates in minerogenic bogs can increase the Hg
      concentrations in the minerogenic peat by a factor of approximately 2 at the same
      atmospheric Hg deposition rate if compared to ombrotrophic sites. This study has
      shown that Hg in minerogenic peat can be naturally enriched especially through
      the retention by autochthonous formed goethite and can be a solely internal
      process which does not require increased external Hg fluxes.

PMID- 15152317
TI  - Historical trace metal fluxes in the Mexico City Metropolitan Zone as evidenced
      by a sedimentary record from the Espejo de los Lirios lake.
AB  - The accumulation of selected trace metals (Ag, Cd, Co, Cr, Cu, Hg, Ni, Pb, V and
      Zn) was studied in a sediment core collected at Espejo de los Lirios lake, a
      precipitation-dominated seepage lake in Northern Mexico City Metropolitan Zone
      (MCMZ). A (210)Pb-derived chronology, obtained from the same core, was used to
      reconstruct the historical metal fluxes at the site, allowing evaluation of the
      impact of environmental changes promoted by the development of the City during
      the last approximately 125 years. The highest levels of metal enrichment above
      natural concentration levels (NCL) in the sediments from Espejo de los Lirios
      lake were found for Ag and Pb (approximately 250%) as well as a slight enrichment
      for Cd (55%), Cr (84%), Co (20%), Cu (60%), Hg (47%), Ni (45%), V (59%) and Zn
      (66%). Fluxes of trace metals appeared to have noticeably increased from the last
      45 years showing the maximum increments for Cd, Co, Cr, Ni, V and Zn during the
      1980's (9 to 13 fold natural fluxes), for Ag and Cu (17 and 12 fold,
      respectively) during the 1990's and for Hg and Pb (2 and 13 fold) during the
      middle 1970's. Low levels of metal enrichment observed have evidenced that the
      most conspicuous consequences of the expansive growth of this area of the MCMZ,
      are mostly related to deforestation and erosion of the surrounding areas, rather
      than to trace metal pollution. Based on PCA, it can be assumed that atmospheric
      deposition, weathering of bedrock and soil within the watershed and authigenic
      production, are the most important processes that explain the trace metal
      distribution in the site.

PMID- 15152318
TI  - Suggested protocol for collecting, handling and preparing peat cores and peat
      samples for physical, chemical, mineralogical and isotopic analyses.
AB  - For detailed reconstructions of atmospheric metal deposition using peat cores
      from bogs, a comprehensive protocol for working with peat cores is proposed. The
      first step is to locate and determine suitable sampling sites in accordance with
      the principal goal of the study, the period of time of interest and the precision
      required. Using the state of the art procedures and field equipment, peat cores
      are collected in such a way as to provide high quality records for
      paleoenvironmental study. Pertinent field observations gathered during the
      fieldwork are recorded in a field report. Cores are kept frozen at -18 degree C
      until they can be prepared in the laboratory. Frozen peat cores are precisely cut
      into 1 cm slices using a stainless steel band saw with stainless steel blades.
      The outside edges of each slice are removed using a titanium knife to avoid any
      possible contamination which might have occurred during the sampling and handling
      stage. Each slice is split, with one-half kept frozen for future studies
      (archived), and the other half further subdivided for physical, chemical, and
      mineralogical analyses. Physical parameters such as ash and water contents, the
      bulk density and the degree of decomposition of the peat are determined using
      established methods. A subsample is dried overnight at 105 degree C in a drying
      oven and milled in a centrifugal mill with titanium sieve. Prior to any expensive
      and time consuming chemical procedures and analyses, the resulting powdered
      samples, after manual homogenisation, are measured for more than twenty-two major
      and trace elements using non-destructive X-Ray fluorescence (XRF) methods. This
      approach provides lots of valuable geochemical data which documents the natural
      geochemical processes which occur in the peat profiles and their possible effect
      on the trace metal profiles. The development, evaluation and use of peat cores
      from bogs as archives of high-resolution records of atmospheric deposition of
      mineral dust and trace elements have led to the development of many analytical
      procedures which now permit the measurement of a wide range of elements in peat
      samples such as lead and lead isotope ratios, mercury, arsenic, antimony, silver,
      molybdenum, thorium, uranium, rare earth elements. Radiometric methods (the
      carbon bomb pulse of (14)C, (210)Pb and conventional (14)C dating) are combined
      to allow reliable age-depth models to be reconstructed for each peat profile.

PMID- 15152319
TI  - Development of an ombrotrophic peat bog (low ash) reference material for the
      determination of elemental concentrations.
AB  - Given the increasing interest in using peat bogs as archives of atmospheric metal
      deposition, the lack of validated sample preparation methods and suitable
      certified reference materials has hindered not only the quality assurance of the
      generated analytical data but also the interpretation and comparison of peat core
      metal profiles from different laboratories in the international community.
      Reference materials play an important role in the evaluation of the accuracy of
      analytical results and are essential parts of good laboratory practice. An
      ombrotrophic peat bog reference material has been developed by 14 laboratories
      from nine countries in an inter-laboratory comparison between February and
      October 2002. The material has been characterised for both acid-extractable and
      total concentrations of a range of elements, including Al, As, Ca, Cd, Cr, Cu,
      Fe, Hg, Mg, Mn, Na, Ni, P, Pb, Ti, V and Zn. The steps involved in the production
      of the reference material (i.e. collection and preparation, homogeneity and
      stability studies, and certification) are described in detail.

PMID- 15152320
TI  - Identifying the sources and timing of ancient and medieval atmospheric lead
      pollution in England using a peat profile from Lindow bog, Manchester.
AB  - A peat core from Lindow bog near Manchester, England, was precisely cut into 2 cm
      slices to provide a high-resolution reconstruction of atmospheric Pb deposition.
      Radiocarbon and (210)Pb age dates show that the peat core represents the period
      ca. 2000 BC to AD 1800. Eleven radiocarbon age dates of bulk peat samples reveal
      a linear age-depth relationship with an average temporal resolution of 18.5 years
      per cm, or 37 years per sample. Using the Pb/Ti ratio to calculate the rates of
      anthropogenic, atmospheric Pb deposition, the profile reveals Pb contamination
      first appearing in peat samples dating from ca. 900 BC which clearly pre-date
      Roman mining activities. Using TIMS, MC-ICP-MS, and SF-ICP-MS to measure the
      isotopic composition of Pb, the (208)Pb/(206)Pb and (206)Pb/(207)Pb data indicate
      that English ores were the predominant sources during the pre-Roman, Roman, and
      Medieval Periods. The study shows that detailed studies of peat profiles from
      ombrotrophic bogs, using appropriate preparatory and analytical methods, can
      provide new insight into the timing, intensity, and predominant sources of
      atmospheric Pb contamination, even in samples dating from ancient times.

PMID- 15152323
TI  - Gary A. Eiceman, New Mexico State University.

PMID- 15152322
TI  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS):--versatility in
      chemical and imaging surface analysis.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has emerged as one of
      the most important and versatile surface analytical techniques available for
      advanced materials research. This arises from its excellent mass resolution,
      sensitivity and high spatial resolution providing both chemical and
      distributional (laterally and depth) information for a wide variety of materials
      and applications. Understanding the various modes of operation and the
      information that each provides is crucial to the analyst in order to optimise the
      type of data that is obtained. New developments in primary ion sources and the
      application of multivariate analysis techniques, which can only extend the
      versatility and applicability of the technique, are also discussed.

PMID- 15152324
TI  - Recent advancements in chemometrics for smart sensors.

PMID- 15152325
TI  - Very high pressure HPLC with 1 mm id columns.
AB  - Theoretical calculations and experimental data indicate that very high pressure
      HPLC can be performed using 1 and 1.5 mm id columns, and contrary to previous
      beliefs, the frictional heating generated does not appear to be detrimental to
      the separation.

PMID- 15152326
TI  - Raman spectroscopy of street samples of cocaine obtained using Kerr gated
      fluorescence rejection.
AB  - The first use of Kerr gated fluorescence rejection Raman spectroscopy for the
      analysis of street samples of cocaine in a fluorescing matrix is reported.

PMID- 15152327
TI  - Fast and simple sample introduction for capillary electrophoresis microsystems.
AB  - A newly designed capillary electrophoresis (CE) microchip with a simple and
      efficient sample introduction interface is described. The sample introduction is
      carried out directly on the separation channel through a sharp inlet tip placed
      in the sample vial, without an injection cross, complex microchannel layouts or
      hardware modification. Alternate placement of the inlet tip in vials containing
      the sample and buffer solutions permits a volume defined electrokinetic sample
      introduction. Such fast and simple sample introduction leads to highly
      reproducible signals with no observable carry over between different analyte
      concentrations. The performance of the system was demonstrated in flow-injection
      and CE measurements of nitroaromatic explosives and for on-chip enzymatic assays
      of glucose in the presence of ascorbic acid. Employing an 8 cm long separation
      channel and a separation voltage of 4000 V it offers high-throughput flow
      injection assays of 100 samples h(-1) with a relative standard deviation of 3.7%
      for TNT (n= 100). Factors influencing the analytical performance of the new
      microchip have been characterized and optimized. Such ability to continuously
      introduce discrete samples into micrometer channels indicates great promise for
      high-speed microchip analysis.

PMID- 15152328
TI  - Carbon-nanotube/copper composite electrodes for capillary electrophoresis
      microchip detection of carbohydrates.
AB  - The preparation of carbon nanotube (CNT)/copper composite electrodes, based on co
      mixing CNT and Cu powders within mineral oil, is described. The new composite
      electrode is used for improved amperometric detection of carbohydrates following
      their capillary electrophoresis (CE) microchip separations. The CNT/Cu composite
      electrode detector displays enhanced sensitivity compared to detectors based on
      copper or CNT alone. The marked catalytic action of the CNT/Cu composite material
      permits effective low potential (+0.5 V vs. Ag/AgCl) amperometric detection, and
      is coupled to the renewability, bulk modification and versatility advantages of
      composite electrodes. The CNT/Cu composite surface also leads to a greater
      resistance to surface fouling compared to that observed at the copper electrode.
      Factors affecting the electrocatalytic activity and the CE microchip detection
      are examined and optimized. The CNT/Cu composite electrode is also shown to be
      useful for the detection of amino acids as indicated from preliminary results.
      While the present work has focused on the enhanced CE microchip detection of
      carbohydrates and amino acids, the CNT/metal-composite electrode route should
      benefit the detection of other important groups of analytes.

PMID- 15152329
TI  - Ophthalmic glucose sensing: a novel monosaccharide sensing disposable and
      colorless contact lens.
AB  - We have developed a technology for continuous tear glucose monitoring, and
      therefore potentially blood glucose monitoring, using a daily use, disposable
      contact lens embedded with sugar-sensing boronic acid containing fluorophores.
      The novelty of our approach is two fold. Firstly, the notion of sensing extremely
      low glucose concentrations in tears by our approach, and secondly, the unique
      compatibility of our new probes with the internal environment of the disposable,
      off-the-shelf, contact lenses, chosen because the physiological compatibility of
      disposable plastic contact lenses has already been assessed and optimized with
      regard to vision correction, size and oxygen/analyte permeability. Our findings
      show that our approach is indeed suitable for the continuous monitoring of tear
      glucose levels in the concentration range (50-500 microM), which track blood
      glucose levels which are approximately 5-10 fold higher. We believe our approach
      offers unique opportunities for non-invasive continuous glucose monitoring for
      diabetics, especially since many have eye disorders and require vision correction
      by either contact lenses or glasses, which is thought to be due to glycation of
      protein in blood vessels.

PMID- 15152330
TI  - Determination of amines as pentafluoropropionic acid anhydride derivatives in
      biological samples using liquid chromatography and tandem mass spectrometry.
AB  - Determination of amines in biological samples as markers of exposure to the
      amines or the corresponding isocyanates is an important tool for industrial
      exposure assessment. In this study, a liquid chromatography and tandem mass
      spectrometry (LC-MS/MS) method for determination of amines in biological samples
      as perfluorofatty amides derivatives is presented. The method enables
      determination of diamines such as methylene diamine (MDA), toluene diamine (TDA),
      naphthalene diamine (NDA), hexamethylene diamine (HDA), isophorone diamine
      (IPDA), methylenedi(cyclohexylamine)(HMDA) and 4,4'-methylene-(2
      chloroaniline)(MOCA) in human urine and plasma. The work-up procedure included
      hydrolysis of the biological samples with 3 M H(2)SO(4) at 100 degrees C for 16 h
      and extraction of the amines into toluene, where derivatisation of the amines
      with perfluorofatty acid anhydride was performed. Following removal of excess
      reagent and the acid formed and an exchange of solvent, the derivatives were
      analysed using gradient elution with an acetonitrile/water mobile phase
      composition and electrospray ionisation (ESI) with multiple reaction monitoring
      (MRM) of [M - H](-)-->[M - H - 120](-) or [119](-). Several perfluorofatty acid
      anhydrides were evaluated as derivatisation reagents, but the LC chromatographic
      properties of the pentafluoropropionic acid anhydride (PFPA) derivatives were
      favourable. Quantification of amine-PFPA derivatives was performed using
      deuterium labelled amine-PFPA derivatives as internals standards with good
      precision and linearity in the investigated range of 0-20 ng ml(-1) urine. The
      instrumental detection limits for the amine-PFPA derivatives were 0.2-3 fmol for
      MRM of [M - H](-)-->[119](-) and 0.3-8 fmol for [M - H](-)-->[M - H - 120](-). In
      10 urine and 6 plasma samples from workers exposed to isocyanates, determination
      of TDA and MDA as PFPA derivatives was performed using LC-MS/MS and a reference
      GC-MS method. No significant difference between the two methods was observed.

PMID- 15152331
TI  - Respiration activity of Escherichia coli entrapped in a cone-shaped microwell and
      cylindrical micropore monitored by scanning electrochemical microscopy (SECM).
AB  - The metabolic activity of E. coli cells embedded in collagen gel microstructures
      in a cone-shaped well and in a cylindrical micropore was investigated using
      scanning electrochemical microscopy (SECM), based on the oxygen consumption rate
      and the conversion rate from ferrocyanide to ferricyanide. The analysis of the
      concentration profiles for oxygen and ferrocyanide afforded the oxygen
      consumption rate and the ferrocyanide production rate. A comparison indicated
      that the ferrocyanide production rates were larger than the oxygen consumption
      rate, and also that the rates observed in the cylindrical micropore were larger
      than those observed in the cone-shaped well. The ferrocyanide production rate of
      a single E. coli cell was calculated to be (5.4 +/- 2.6) x 10(-19) mol s(-1),
      using a cylindrical micropore system.

PMID- 15152332
TI  - A metabonomic investigation of the biochemical effects of mercuric chloride in
      the rat using 1H NMR and HPLC-TOF/MS: time dependent changes in the urinary
      profile of endogenous metabolites as a result of nephrotoxicity.
AB  - The effects of the administration of a single dose of the model nephrotoxin
      mercuric chloride (2.0 mg kg(-1), subcutaneous) to male Wistar-derived rats on
      the urinary metabolite profiles of a range of endogenous metabolites has been
      investigated using (1)H NMR and HPLC-MS. Urine samples were collected daily for 9
      days from both dosed and control animals. Analysis of these samples revealed
      marked changes in the pattern of endogenous metabolites as a result of HgCl(2)
      toxicity. Peak disturbances in the urinary metabolite profiles were observed
      (using both NMR and HPLC-MS) at 3 days post dose. Thereafter the urinary
      metabolite profile gradually returned to a more normal composition. Markers of
      toxicity identified by (1)H NMR spectroscopy were raised concentrations of
      lactate, alanine, acetate, succinate, trimethylamine (TMA), and glucose.
      Reductions in the urinary excretion of citrate and alpha-ketoglutarate were also
      seen. Markers identified by HPLC-MS, in positive ion mode, were kynurenic acid,
      xanthurenic acid, pantothenic acid and 7-methylguanine which decreased after
      dosing. In addition an ion at m/z 188, probably 3-amino-2-naphthoic acid, was
      observed to increase after dosing. As well as these identified compounds other
      ions at m/z 297 and 267 decreased after dosing. In negative ion mode a range of
      sulfated compounds were observed, including phenol sulfate and benzene diol
      sulfate, which decreased after dosing. As well as the sulfated components an
      unidentified glucuronide at m/z 326 was also observed to decrease after dosing.
      The results of this study demonstrate the complementary nature of the NMR and MS
      based techniques for metabonomic analysis.

PMID- 15152333
TI  - Fast automatic registration of images using the phase of a complex wavelet
      transform: application to proteome gels.
AB  - Image registration describes the process of manipulating a distorted version of
      an image such that its pixels overlay the equivalent pixels in a clean, master or
      reference image. The need for it has assumed particular prominence in the
      analysis of images of electrophoretic gels used in the analysis of protein
      expression levels in living cells, but also has fundamental applications in most
      other areas of image analysis. Much of the positional information of a data
      feature is carried in the phase of a complex transform, so a complex transform
      allows explicit specification of the phase, and hence of the position of features
      in the image. Registration of a test gel to a reference gel is achieved by using
      a multiresolution movement map derived from the phase of a complex wavelet
      transform (the Q-shift wavelet transform) to dictate the warping directly via
      movement of the nodes of a Delaunay-triangulated mesh of points. This warping map
      is then applied to the original untransformed image such that the absolute
      magnitude of the spots remains unchanged. The technique is general to any type of
      image. Results are presented for a simple computer simulated gel, a simple real
      gel registration between similar "clean" gels with local warping vectors
      distributed about one main direction, a hard problem between a reference gel and
      a "dirty" test gel with multi-directional warping vectors and many artifacts, and
      some typical gels of present interest in post-genomic biology. The method
      compares favourably with others, since it is computationally rapid, effective and
      entirely automatic.

PMID- 15152334
TI  - Rapid dioxin assessment in fish products by fatty acid pattern recognition.
AB  - A novel, cost- and time-effective dioxin screening method relying on fatty acid
      profile was developed for fish products. The method is based on multivariate
      covariance between fatty acid composition and dioxin. A dioxin range varying from
      1.1 to 47.1 ng TEQ-WHO kg fat(-1) was investigated using 64 fish meal samples. An
      optimal multivariate dioxin prediction model was developed based on reduction
      from the original 32 to 13 fatty acids, thus increasing the parsimony and the
      robustness of the model. The model obtained with three partial least squares
      regression (PLS) components included the following 13 fatty acids: C14:1 n-5,
      C16:4 n-1, C18:1 n-9, C18:2 n-6, C18:3 n-6, C18:3 n-3, C20:0, C20:1 n-9, C20:4 n
      6, C20:3 n-3, C22:1 n-7, C22:6 n-3, C24:1 n-9. Considering the whole investigated
      dioxin range, the performance of the PLS model based upon full cross-validation
      yielded a correlation of 0.90 (r(2)) and a prediction error of 3.31 ng PCDD/F TEQ
      WHO kg fat(-1). A submodel of samples in the lower dioxin range 1 to 15 ng PCDD/F
      TEQ-WHO kg fat(-1) returned a r(2) of 0.88 and an error of 1.85 ng PCDD/F TEQ-WHO
      kg fat(-1).

PMID- 15152335
TI  - Non-destructive analysis of the two subspecies of African elephants, mammoth,
      hippopotamus, and sperm whale ivories by visible and short-wave near infrared
      spectroscopy and chemometrics.
AB  - Visible (VIS) and short-wave near infrared (SW-NIR) spectroscopy was used for non
      destructive analysis of ivories. VIS-SW-NIR (500-1000 nm) spectra were measured
      in situ for five kinds of ivories, that is two subspecies of African elephants,
      mammoth, hippopotamus, and sperm whale. Chemometrics analyses were carried out
      for the spectral data from 500 to 1000 nm region. The five kinds of ivories were
      clearly discriminated from each other on the scores plot of two principal
      components (PCs) obtained by principal component analysis (PCA). It was
      noteworthy that the ivories of the two subspecies of African elephants were
      discriminated by the scores of PC 1. The loadings plot for PC 1 showed that the
      discrimination relies on the intensity changes in bands due to collagenous
      proteins and water interacting with proteins. It was found that the scores plot
      of PC 2 is useful to distinguish between the ivories of the two subspecies of
      African elephants and the other ivories. We also developed a calibration model
      that predicted the specific gravity of five kinds of ivories from their VIS-SW
      NIR spectral data using partial least squares (PLS)-1 regression. The correlation
      coefficient and root mean square error of cross validation (RMSECV) of this model
      were 0.960 and 0.037, respectively.

PMID- 15152336
TI  - [An appeal for psychiatric foundations].

PMID- 15152337
TI  - [Illness related costs for spouses of patients suffering from a mental illness:
      results of a study with repeated measurements].
AB  - OBJECTIVE: Aim of this study is the documentation of illness-associated costs for
      spouses, whose relative is suffering from a mental illness. METHOD: Over a period
      of 12 month, 117 spouses of patients who are suffering from schizophrenia,
      depression or anxiety disorders repeatedly filled in a standardized questionnaire
      about illness related expenses and financial losses. RESULTS: 90 % of the spouses
      reported direct cash expenditures on behalf of the patients' illness. On average,
      these costs amounted to yearly expenditures of euro 1146 (range: euro 0 - 11
      910). Costs did not differ significantly across types of illness and income was
      not found to be a significant covariate. CONCLUSIONS: Spouses reported
      substantial direct cash expenditures on behalf of the patients' illness. Since
      these expenditures varied to a large extent over the three points of measurement,
      repeated measurement designs seem to be a prerequisite for a reliable assessment
      of illness-associated costs. Since living together with a mentally ill partner is
      associated with an increased risk of developing a burden-related psychiatric
      illness for spouses themselves which may lead to double costs and double
      decreases in income, these aspects should be taken into consideration when
      planning changes in health policy.

PMID- 15152338
TI  - ["Suddenly, no more money was left". The role of financing in the Austrian mental
      health care reform].
AB  - OBJECTIVE: The article studies the role of financing mental health care for the
      mental health care service structure in the process of moving towards a patient
      oriented and decentralised mental health care system. METHOD: The analysis is
      based on a description of the Austrian mental health care financing system and a
      discourse-analytical examination of reform documents and interviews with key
      actors in this country. RESULTS: Existing structures of mental health care
      services are a reflection of mental health care financing structures. Reform
      goals are in various forms linked to financing issues. However, an explicit
      discussion of the finance issues in reform documents is widely missing.
      CONCLUSIONS: Adapting the finance of mental health care to new paradigms of
      mental health care provision requires not just technical modifications, but also
      improved transparency of processes and implications involved.

PMID- 15152339
TI  - [Deinstitutionalization of long-stay psychiatric patients in upper austria -
      living situation, social and clinical characteristics more than one year after
      discharge].
AB  - OBJECTIVE: In Upper Austria, a total of 409 long-stay patients were discharged to
      various residential facilities between 1995 and 2000. This paper describes
      psychopathology and sociodemographic characteristics. METHODS: A random sample of
      116 former long-stay patients were followed for an average 42.9 months after
      discharge. RESULTS: Patients had spent an average 19.3 years in psychiatric
      wards. 47 patients (40.5 %) were placed in nursing homes, 16 patients (13.8 %) in
      old-age homes, 32 patients (27.6 %) in other institutions and only 15 patients
      (12.9 %) in group homes, and 6 patients (5.2 %) with families. ICD-10 diagnosis
      was schizophrenia in 56 patients (48.3 %) and mental retardation in 33 patients
      (28.4 %). Level of social and functional disabilities was high. CONCLUSIONS: Most
      long-stay patients were able to live outside psychiatric hospitals, but
      institutional care still plays an essential role.

PMID- 15152340
TI  - [The visit at home by a social worker of a psychiatric outpatient clinic].
AB  - OBJECTIVE: The high rank of social work in context with psychiatric treatment of
      in-patients is generally accepted. The value of social work and here especially
      the visit at home by the social worker has hardly been examined up to now.
      METHOD: In the article first of all the method of visits at home is presented.
      Furthermore all visits at home by a female social worker of an outpatient clinic
      over a period of three years are retrospectively evaluated. RESULTS: In
      connection with 28 patients (54 +/- 14 years old) 218 visits - in total - were
      carried out. It is remarkable that - apart from one case - the patients were at
      home and the social worker was admitted to their private rooms. By far most
      frequently the emphasis of the visit at home was assigned to the solution of
      actual problems within the framework of a long-term socio-therapeutic process.
      CONCLUSIONS: In further discussion it will be crucial to work out indications and
      contraindications as well as directives for technical execution and - if
      necessary - to develop differential indications for different types of visits at
      home for different groups of patients.

PMID- 15152341
TI  - [Disability payments due to unipolar depressive and bipolar affective disorders].
AB  - OBJECTIVE: Little is known concerning the frequency of disability payments due to
      depressive and bipolar affective disorders in Germany. METHOD: 177 consecutive
      psychiatric in-patients were assessed with standardized interviews concerning
      diagnosis (SCID-I, DSM-IV) and illness history. To compare unipolar depressive
      and bipolar affective patients, a survival analysis was calculated. RESULTS: 116
      patients suffered from unipolar depression, 61 from bipolar affective disorder.
      Highly significantly, patients with bipolar affective disorders were granted
      disability payments more frequently and at an earlier age. Half of the bipolar
      affective patients received disability payments by the age of 46 years, half of
      the unipolar depressive patients by the age of 58 years. CONCLUSIONS: In this
      sample, bipolar affective patients received disability payments frequently and at
      an early age, which stresses that the prognosis of bipolar affective disorders is
      not as good as has been assumed for a long time. Early disability payments may
      lead to poverty and may obstruct access to social rehabilitation.

PMID- 15152342
TI  - [The sequential traumatisation of a Sinti-child Holocaust-survivor].
AB  - The subject of this case-report is the life-history, nosogenesis and history of
      compensation claims of a 64-years old Sinti-woman, who survived Nazi-persecution
      and WWII as a child. She and her mother spent 3 years in a concentration camp. At
      the end of the war she witnessed her mothers death. Her life is characterised by
      psychosomatic symptoms, disorders of psychosexual development, including
      infertility, and a chronic Post Traumatic Stress Disorder. The non-treated course
      of the Holocaust survivor syndrom, described by Niederland, which was mostly
      denied in Germany, could be now shown by detailed exploration and the reanalysis
      of former expert reports of her symptoms. Furthermore, this case report presents
      the internationally described characteristics of long-term effects in children
      that have survived the Holocaust. These symptoms are typical of cases that were
      not been treated throughout life. The former lack of acceptance in Germany of
      these long-term effects has - like in this and other cases - lead to development
      into a chronic disorder.

PMID- 15152343
TI  - Theoretical and empirical power of regression and maximum-likelihood methods to
      map quantitative trait loci in general pedigrees.
AB  - Both theoretical calculations and simulation studies have been used to compare
      and contrast the statistical power of methods for mapping quantitative trait loci
      (QTLs) in simple and complex pedigrees. A widely used approach in such studies is
      to derive or simulate the expected mean test statistic under the alternative
      hypothesis of a segregating QTL and to equate a larger mean test statistic with
      larger power. In the present study, we show that, even when the test statistic
      under the null hypothesis of no linkage follows a known asymptotic distribution
      (the standard being chi(2)), it cannot be assumed that the distribution under the
      alternative hypothesis is noncentral chi(2). Hence, mean test statistics cannot
      be used to indicate power differences, and a comparison between methods that are
      based on simulated average test statistics may lead to the wrong conclusion. We
      illustrate this important finding, through simulations and analytical
      derivations, for a recently proposed new regression method for the analysis of
      general pedigrees to map quantitative trait loci. We show that this regression
      method is not necessarily more powerful nor computationally more efficient than a
      maximum-likelihood variance-component approach. We advocate the use of empirical
      power to compare trait-mapping methods.

PMID- 15152344
TI  - Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype
      analysis of 37 families with ataxia.
AB  - We reported elsewhere that an untranslated CTG expansion causes the dominantly
      inherited neurodegenerative disorder spinocerebellar ataxia type 8 (SCA8). SCA8
      shows a complex inheritance pattern with extremes of incomplete penetrance, in
      which often only one or two affected individuals are found in a given family.
      SCA8 expansions have also been found in control chromosomes, indicating that
      separate genetic or environmental factors increase disease penetrance among SCA8
      expansion-carrying patients with ataxia. We describe the molecular genetic
      features and disease penetrance of 37 different families with SCA8 ataxia from
      the United States, Canada, Japan, and Mexico. Haplotype analysis using 17 STR
      markers spanning an approximately 1-Mb region was performed on the families with
      ataxia, on a group of expansion carriers in the general population, and on
      psychiatric patients, to clarify the genetic basis of the reduced penetrance and
      to investigate whether CTG expansions among different populations share a common
      ancestral background. Two major ancestrally related haplotypes (A and A') were
      found among white families with ataxia, normal controls, and patients with major
      psychosis, indicating a common ancestral origin of both pathogenic and
      nonpathogenic SCA8 expansions among whites. Two additional and distinct
      haplotypes were found among a group of Japanese families with ataxia (haplotype
      B) and a Mexican family with ataxia (haplotype C). Our finding that SCA8
      expansions on three independently arising haplotypes are found among patients
      with ataxia and cosegregate with ataxia when multiple family members are affected
      further supports the direct role of the CTG expansion in disease pathogenesis.

PMID- 15152345
TI  - [Dementia and cognitive impairment pattern: its association with epsilon4 allele
      of apolipoprotein E gene].
AB  - INTRODUCTION: The APOE epsilon4 allele is a well-established risk factor for
      Alzheimer's disease. This disease is characterized by a typical progressive
      cognitive impairment pattern, different from that of other primary dementias such
      as dementia with Lewy bodies or frontotemporal and vascular dementias, for which
      there are no conclusive results on the influence of the APOE genotype. OBJECTIVE:
      Our aim is to study how the APOE genotype associates with different dementia
      types, and the association of this genotype with mild cognitive impairment and
      age related cognitive decline, which might be stages in a continuum between
      normality and dementia. PATIENTS AND METHODS: From a group of 1,022 people we
      selected 733 patients with different dementia diagnosis and 205 controls. APOE
      genotype for each participant in the study was determined. RESULTS: As it was
      already known, the epsilon4 allele is associated to senile Alzheimer's disease
      (OR= 5.6; 95% CI= 3.6-8.9; p< 0.001) and presenile Alzheimer's disease (OR= 5.4;
      95% CI= 2.1-13.8; p< 0.001). It is also associated to mild cognitive impairment
      (OR= 3.7; 95% CI= 2.3-6.0; p< 0.001) and to age related cognitive decline (OR=
      3.0; 95% CI= 1.2-7.3; p< 0.01). Female Alzheimer patients with at least one
      epsilon4 allele present significantly an earlier age at onset (epsilon4+= 73.4 +/
      5.4; epsilon4- = 76.9 +/- 5.5; p< 0.001). CONCLUSION: The APOE genotype is
      associated to Alzheimer's disease and to its cognitive impairment pattern. This
      association has a growing value according to the degree of clinical impairment.
      The APOE genotype could be used in differential diagnostic of cognitive
      impairment.

PMID- 15152346
TI  - [Neonatal seizures, our experience].
AB  - AIM: To study retrospectively all newborns admitted between 1992 and 1998 in our
      Neonatology Unit with convulsions before 30 days of life. PATIENTS AND METHODS:
      77 patients, 63.6% male, with an average gestational age of 36.42 weeks, and an
      average birth weight of 2,653 g. Apgar score at five minutes was below 4 in 4
      newborns. RESULTS: In 35 patients the first convulsion occurred in the first 48
      hours of life, 7 patients showed status epilepticus. There was a single type of
      seizure in 49 newborns (65.3%), specially tonic and clonic (multifocal and
      focal). Head ultrasound was abnormal in 33 newborn, CT scan and/or MRI abnormal
      in 24, EEG was pathologic in 55. Phenobarbital was the initial treatment in
      81.8%, half of them required a therapeutical change. 34 patients (55.7%) still
      received treatment at hospital discharge. The etiology was hypoxic ischaemic
      encephalopathy (39%), though less important than in previous studies,
      intracranial hemorrhage (13%), central nervous system malformations (9%), among
      other. 16 patients died, 35 showed an abnormal outcome (45.4%): cognitive delay
      in 24, epilepsy in 19, motor abnormalities in 12. CONCLUSION: The worst outcome
      was found in malformations, meningitis, intracranial hemorrhages, metabolic
      diseases and hypoxic ischaemic encephalopathy, while the best in hypoglycemia and
      in benign idiopathic neonatal seizures.

PMID- 15152347
TI  - [Ultrasonography in diagnosis and monitoring the progress of dissection of
      cervicocerebral arteries].
AB  - INTRODUCTION: Ultrasonography has become part of the arsenal of diagnostic
      methods available for examining the dissection of cerebral blood vessels (DCV).
      AIMS: To analyse the value of ultrasonography in the diagnosis and monitoring of
      DCV. PATIENTS AND METHODS: We conducted a consecutive study of 67 patients with a
      history and clinical picture compatible with DCV; all of them had been given
      confirmation of their diagnosis by another reference method (digital angiography
      or MR angiography) during the 48 hours prior to or following the ultrasound
      study. The ultrasonography was carried out on the neck and skull as per the usual
      system using continuous Doppler, neck duplex and transcranial Doppler
      ultrasonography. Diagnosis of the dissection was based on direct and indirect
      signs, in the absence of an atheroma plaque. The following were considered to be
      direct signs: haematoma in the wall of the vessel, flap, local increase in the
      flow velocity and echograms with split systole. Indirect signs were: haemodynamic
      alterations proximal to the dissection, a pattern of slow flow and high
      resistance. The transcranial Doppler showed the findings lying distal to the
      dissection to be a lowered mean velocity and pulsatility. RESULTS: The
      ultrasonography of the series revealed direct signs in 46 patients (69%) and
      indirect signs in 21 (31%). Ultrasonography was used as the primary diagnostic
      method in 29 (43%) patients; in the other 38 (57%) it was employed to verify the
      diagnosis or for the follow up. All the ultrasound diagnoses were confirmed using
      digital angiography (21 cases) or magnetic resonance angiography (46 cases).
      CONCLUSIONS: Due to its harmlessness, ultrasonography should be the first
      examination used to establish a probable diagnosis of DCV.

PMID- 15152348
TI  - [Clinical features of multiple sclerosis in Western Cuba. A comparison with two
      other regions in the country].
AB  - INTRODUCTION: Multiple sclerosis (MS) is an inflammatory disease in its early
      stages whose primary or secondary immunological mechanisms produce reversible or
      irreversible lesions in the myelin and axons in the central nervous system. The
      first case of MS in Cuba was reported in 1965. Current prevalence of MS is
      considered to be 10 cases/100,000 inhabitants. AIMS: The aim of this study was to
      characterise MS in Western Cuba from a clinical point of view and in comparison
      with other similar studies carried out in two other regions in the country.
      PATIENTS AND METHODS: 50 patients living in the western region were clinically
      assessed. Statistical tests were carried out to compare this survey with two
      similar studies conducted in the central and eastern regions. RESULTS: 80% of our
      patients were females, predominantly white skinned, the main events in their
      family histories were neurological diseases and psychiatric diseases, essentially
      schizophrenia, the chief triggering event being psychic tension, the most
      frequent form of progression was the remittent recurring form, followed by
      secondary progressive form, and then the primary progressive; the main symptoms
      at onset were visual, followed by pyramidal and sensory; the most strongly
      affected functional system was the pyramidal and then the sensory system; the
      functional systems are more affected in the primary progressive form, except the
      visual and the brainstem; the largest group of patients corresponded to those
      that had a history of over 10 years with the disorder. By far the majority of
      results compared with the series from the central region and from Santiago de
      Cuba were similar, but some significant differences did appear on comparing these
      two series. CONCLUSIONS: The study shows the characteristics of the disease in
      the Western region valuated using distinct parameters and several differences
      between the three series can be observed fundamentally with regard to skin
      colour, triggering events, symptoms at onset and functional involvement in the
      forms of progression.

PMID- 15152349
TI  - ['5 digit test': a multilinguistic non-reading alternative to the Stroop test].
AB  - INTRODUCTION: The use of digits in groups that may or may not correspond to their
      arithmetic values (for instance: five twos, that can be easily read as 'two', but
      must be counted as a 'five') allows us to measure at the same time the
      'processing speed' of the subjects and their ability to 'direct' and 'switch'
      their attentional control. AIMS: The use of this new 'five digit test' (5DT) as a
      multilingual non-reading alternative to the Stroop test presents a series of
      advantages: it minimizes the effects of education and social class, allows the
      testing of much younger students, and allows the testing of some severe clinical
      cases, who may not be able to read words or name colors. SUBJECTS AND METHODS:
      Using groups of 20 adults at different age levels (55-64, 65-74, 75+) and groups
      of 20 and 20 subjects with cerebral-vascular episodes (anterior and posterior) we
      can estimate the usefulness of this instrument in concrete nosological
      populations. RESULTS: We find a slowing of production and reorientation times
      with aging; and a dramatic influence of neurological dysfunctions. CONCLUSIONS:
      The tests allows a valid exploration of the Stroop effect in prereading and non
      reading subjects, even in other languages.

PMID- 15152350
TI  - [The use of olanzapine in sleep disorders. An open trial with nine patients].
AB  - INTRODUCTION: The impossibility of treating patients with sleep disorders
      adequately means that, as specialists, we have to look for new pharmacological
      treatments and for this reason we examined the information in the paper by Salin
      Pascual (1999) about the increase in deep sleep when olanzapine is used as an
      antipsychotic drug. CASE REPORTS: We decided to use this medication in six
      females and three males who were suffering from different sleep disorders that
      conditioned their chronic insomnia. The dosages of olanzapine used ranged from
      2.5 and 10 mg in a single dose. The clinical history and progress were used to
      elaborate the results and conclusions. The result was positive in eight of the
      nine patients, five who were administered the medication as monotherapy and three
      as polytherapy. CONCLUSION: The population studied is insufficient to prove the
      effectiveness of the drug, but the fact that in eight of our patients the
      treatment clearly improved their symptoms leads us to think that this line of
      research must be continued.

PMID- 15152351
TI  - [Multiple sclerosis and neurocysticercosis: a diagnostic dilemma].
AB  - INTRODUCTION: Both Multiple Sclerosis (MS) and Neurocysticercosis (NC) are two
      entities in which clinical manifestations, neuroimaging findings and
      immunoserologic assays are neither pathognomonic nor specific requiring for their
      diagnosis an accurate examination of the clinical history of patients and an
      adequate follow up. CASE REPORTS: Two patients who consulted non neurologists
      about focal neurological symptoms. Neuroimaging findings revealed multiple
      lesions, some of them contrast enhanced. A diagnosis of neurocysticercosis was
      established, supported in one of the patients by positive serologic assays for
      cysticerci and antihelmintic therapy began to be administered. Observing the
      clinical evolution of the patients, monitoring their clinical history and
      considering the diagnostic criteria proposed by McDonald for MS and by Del Brutto
      for NC the patients were finally diagnosed of MS. CONCLUSION: The first step to
      reach a diagnosis of MS is to consider such a possibility. The diagnosis is
      mainly based on clinical grounds and it is necessary to prove that symptoms
      disseminate or that alterations occur in neuroimaging findings both in time and
      space. It is of the utmost importance to establish a differential diagnosis with
      other conditions presenting with similar clinical manifestations, neuroimaging
      findings and cerebrospinal fluid tests results. Even with the latest criteria
      proposed for the diagnosis of MS and NC we may have doubts making it fundamental
      to cautiously interpret the clinical manifestations and tests results.

PMID- 15152352
TI  - [Fatal rhabdomyolysis in an 8-year-old female].
AB  - INTRODUCTION: Rhabdomyolysis is a syndrome characterised by the destruction of
      muscle fibres which results in the release of toxic intracellular metabolites
      into the circulatory system. It usually has a benign progression but can have
      serious, potentially fatal, complications that largely depend on the cause.
      Disorders affecting the metabolism of energy in muscles can manifest as recurring
      rhabdomyolysis, which usually has kidney failure as its most common complication.
      CASE REPORT: An 8 year old girl who had suffered an episode of rhabdomyolysis one
      year earlier and later died in the Paediatric Intensive Care Unit while suffering
      from acute symptoms of rhabdomyolysis and refractory shock. A muscular biopsy
      specimen was collected, but it was not possible to establish a diagnosis from
      that sample. CONCLUSIONS: Even with all today's progress in the biochemical,
      molecular and genetic fields, the cause of recurring rhabdomyolysis is not easy
      to identify. What stands out in this case is the fatal progression of a usually
      benign problem, whose most serious complication is considered to be the delayed
      production of kidney failure when there is severe decompensation that does not
      receive adequate treatment. We recommend having guidelines set out for the
      correct collection, preparation and storage of the biological samples needed for
      the biochemical, enzymatic, immunohistochemical and DNA studies that can provide
      a diagnosis when death due unknown causes occurs. We emphasise the fact that it
      is the doctor's duty and right to exhaust all the diagnostic possibilities
      available.

PMID- 15152353
TI  - [Cerebellar glioblastoma multiforme: a case report].
AB  - INTRODUCTION: Cerebellar glioblastoma multiforme (CGM) accounts for less than 1%
      of all intracranial glioblastomas; it spreads quickly locally, above all towards
      the brain stem and adjacent leptomeninges, and has a poor prognosis. CASE REPORT:
      We report the case of a 55 year old patient who presented a continuous feeling of
      dizziness, instability and sickness, with occasionally vomiting and double vision
      that had started two months before being admitted to hospital. A physical
      exploration revealed hypaesthesia of the right side of the face, tactile and
      algesic hypaesthesia in the left side of the body and nystagmus in the bilateral
      horizontal gaze. Results of the general physical exploration were normal. A
      magnetic resonance (MR) brain scan revealed a 3 cm expansive lesion in the middle
      cerebellar peduncle and right cerebellar hemisphere, which was hypointense in T1
      and hyperintense in T2. Administering contrast showed it to be heterogeneous,
      with irregular annular enhancement, and perilesional edema. Subtotal excision of
      the lesion was performed and pathological analysis allowed a diagnosis of
      glioblastoma multiforme to be made; radio and chemotherapy were continued.
      CONCLUSION: CGM is infrequent and 46.7 years is the mean age of onset. 59% of
      tumours are located in the hemispheres, they tend to spread locally, and remote
      metastases have also been reported. Initial clinical manifestations are
      intracranial hypertension, and gait and balance disorders. Differential diagnosis
      is provided by MR and includes metastasis, infarction and abscesses. Treatment
      involves radical surgical excision followed by local radiotherapy. The use of
      chemotherapy has been reported but its role in the treatment of this entity is
      still not altogether clear.

PMID- 15152354
TI  - [The extracellular matrix of the central nervous system: chondroitin sulphate
      type proteoglycans and neural repair].
AB  - AIM: In this paper we present a review of the main features of the extracellular
      matrix (ECM) of the central nervous system (CNS). DEVELOPMENT: Proteoglycans (PG)
      are glycoproteins, a very common type of protein in the ECM. Among the PG, the
      most abundant type is the hyalectan or lectican family. The PG is formed by two
      main components; a protein and a sugar chain, which that is termed
      glycosaminoglycan (GAG). These GAGs are polymers of two simple sugars. The
      hyalectan family has GAGs of the Chondroitin sulphate type (CS), and for this
      reason they are termed PG-CS. PG-CS are linked to the hyaluronic acid (HA) and
      other molecules of the ECM in order to form a three-dimensional network. This
      network has several important roles in the maintenance of the homeostasis of the
      CNS. CONCLUSIONS: Several hypotheses have been proposed to elucidate the failure
      of the CNS regeneration after an injury or in several pathologies. It has been
      suggested that PG-CS, which expression is up-regulated after CNS injury, may play
      some role in this process of inhibition of the CNS regeneration. Furthermore, we
      present an approach to the therapeutic potential of the CNS regeneration after
      the inactivation of the PG-CS up-regulation.

PMID- 15152355
TI  - [Pragmatic impairments following traumatic brain injury].
AB  - OBJECTIVE: To describe how cognitive impairments contribute to the loss of
      communicative competence after traumatic brain injury (TBI), what instruments can
      be used to evaluate the pragmatic skills and which therapeutic approaches may be
      used to improve or compensate for this deficit. DISCUSSION: We present a detailed
      bibliographic review on the topic that shows how certain functions (namely,
      memory, attention and executive functions) interact with communication skills,
      both expressive and comprehensive. The pragmatic approaches for cognitive
      communicative TBI impairments are allow to count typical difficulties that are
      described (difficulty with topic selection, turn-taking initiation, ability to
      respond or give indirect requests, ability to meet the informational needs of the
      listener, appropriateness of utterances within conversation, etc). Next a general
      outline of the assessment and treatment of is provided, including several
      strategies based on recovery and functional adaptation and compensation.
      CONCLUSIONS: Given the huge influence of communicative skills on social and
      vocational integration, it is crucial to obtain a better understanding of the
      interaction between cognitive functions and communicative skills. Therefore, we
      need to devise assessment protocols specifically designed for Spanish speakers as
      well as new therapeutic approaches to increase the life quality of this
      population. The specific approaches to improve narrative, procedural and
      conversational discourse must divide from the components of the pragmatic
      competence and promote the cooperative participation of the teamwork who attend
      to the patient.

PMID- 15152356
TI  - [Type 1 glucose transporter (Glut1) deficiency: manifestations of a hereditary
      neurological syndrome].
AB  - AIM: To define this genetic syndrome. DEVELOPMENT: The constellation of infantile
      epilepsy, acquired microcephaly and hypoglychorrachia is characteristic of
      glucose transporter type 1 (Glut1) deficiency syndrome, a prototype
      neurometabolic disorder caused by inheritable mutations in the gene SLC2A1. All
      known mutations reduce the function of Glut1 in the blood brain barrier and thus
      limit brain glucose availability. As the cerebral metabolic rate for glucose
      increases during infancy, patients become gradually symptomatic, a phenomenon
      that underscores the importance of early diagnosis via lumbar puncture and
      treatment, which has meet with some success in ameliorating several --but not all
      - features of the disease. CONCLUSION: The increasing number of mild phenotypic
      variants being described, owing to the improved awareness of the disease, has led
      to the consideration of Glut1 deficiency in the diagnosis of infantile seizures,
      mental retardation, familial epilepsy and movement disorders.

PMID- 15152357
TI  - [Antidepressants in migraine prophylaxis: an approximation].
AB  - INTRODUCTION: Migraine is one of the most frequently observed neurological
      problems in primary health care centres, while major depressive disorder (MDD) is
      the most prevalent mental disorder in the general population. It has been
      observed that emotional factors can trigger or worsen bouts of migraine and there
      is a high rate of comorbidity between migraine and MDD in the general population.
      50% of patients formally diagnosed as suffering from migraine also meet MDD
      criteria. The association found between these clinical entities is complex and
      not casual: it is not simply a matter of an emotional response to the recurring
      headaches. AIM: Our aim was to report on the value of antidepressants in the
      prophylaxis of migraine. DEVELOPMENT: The following have all been used in
      migraine prophylaxis: alpha2-agonists, calcium channel antagonists,
      anticonvulsive drugs, antidepressants, beta blockers, magnesium and
      serotoninergic agents, among others. It has been reported that antidepressant
      drugs with an important agonistic action on 5-HT2 receptors are useful in the
      prophylaxis of migraine. Furthermore, some antidepressants exert a direct
      analgesic effect and modulate the response to pain by means of neuronal
      mechanisms. CONCLUSIONS: Antidepressants are undoubtedly the best alternative
      available for prophylaxis in patients who present migraine associated to MDD.
      Amitriptyline has proved itself to be effective in dosages ranging from 30 to 150
      mg/day, while recent studies have also shown fluoxetin to be effective in doses
      of between 20 and 40 mg/day. Moreover, in general, antidepressants are drugs with
      a low risk of toxicity and few serious or very troublesome side effects.

PMID- 15152358
TI  - [The effects of the social environment on the brain].
AB  - AIMS: This work analyses the main studies dealing with the mechanisms by which
      the brain is altered by chronic stress and the impact of social stimuli on the
      activation of these mechanisms, which can lead to behavioural disorders and
      cognitive impairment in communities of mammals. DEVELOPMENT: The physiological
      and hormonal responses triggered as a response to stress are linked to
      alterations in certain areas of the brain and more particularly in the
      hippocampus. These mechanisms include hyperactivity of the hypothalamus-pituitary
      adrenal axis, raised levels of corticosteroids and excitatory amino acids,
      neurotoxicity due to intracellular accumulation of calcium, apoptosis and a
      number of factors having to do with the immunological system. Most of these
      studies have involved the exogenous application of supraphysiological levels of
      corticosteroids or challenging the individual with stimuli that do not properly
      belong to their natural surroundings. Nevertheless, it is also possible that
      these mechanisms are triggered by aversive social stimuli from the natural
      environment, such as confrontation, establishing hierarchies, neglect and social
      evaluation. It has been proved that social stress has important effects on
      conduct and health, especially with regard to the structural and functional
      integrity of the brain. CONCLUSIONS: Social stress can trigger important
      alterations in the nervous system of individuals exposed to it and these changes
      can manifest themselves as varying types of disorders affecting conduct and the
      cognitive skills. Nevertheless, not all natural surroundings give rise to these
      adverse effects, as balanced communities offer their members support, protection
      and a series of other advantages.

PMID- 15152359
TI  - [A practical guide to carrying out neurophysiological monitoring in spine
      surgery].
AB  - INTRODUCTION AND AIMS: The main purposes of intraoperative monitoring during
      spine surgery are to avoid damage to nerve structures, to guide the surgeon in
      the extension of the correction, to identify structures and to ensure the patient
      receives the best possible attention. Several multicentre studies have shown that
      performing neurophysiological monitoring of spinal cord functioning during spine
      surgery reduces the incidence of post surgical neurophysiological injury by up to
      50%. A number of different neurophysiological tests have been developed to
      monitor spinal cord functioning during surgery but no agreement has been reached
      about which is the best method. In this work, the Spanish Society of Clinical
      Neurophysiology, through a panel of experts, has surveyed the main monitoring
      techniques used during spine surgery and has drawn up a series of best practice
      guidelines. DEVELOPMENT: None of the techniques described to date is totally free
      of drawbacks. Nevertheless, what authors do agree about, both in the Spanish and
      international literature, is the advisability of having several types of
      potential available so that they can be used if and when the neurophysiologist
      sees fit, while also allowing the disadvantages of each different type to be
      compensated, which in turn means an increased degree of safety for the patient.
      CONCLUSIONS: Monitoring requires a multidisciplinary team and the
      neurophysiologist must be fully competent in this area. With this guide, the
      Spanish Society of Clinical Neurophysiology conducts a review of the different
      techniques available and lays down the criteria for interpreting the results and
      the risk criteria of the most important techniques.

PMID- 15152360
TI  - [Neurological paleopathology in the pre-Columbine cultures of the coast and the
      Andean plateau (II). The history of cranial trepanations].
AB  - INTRODUCTION AND AIMS: Trepanation is one of the earliest examples of a surgical
      procedure being carried out by human beings and was performed from the Neolithic
      period onwards in a large number of primitive cultures throughout the five
      continents. Trepanation and cranial deformation were both common in the pre
      Columbine cultures. The aim of this work was to study the trepanations carried
      out by the ancient Paraca, Nazca, Huari, Tiahuanaco and Inca cultures. To do so,
      we conducted a field study involving visits to archaeological remains and
      anthropological museums on the Andean plateau and the Peruvian coast.
      DEVELOPMENT: In the pre-Columbine cultures, trepanation was performed on both men
      and women for therapeutic purposes (depressed fractures, epilepsy, vascular
      headaches and those associated to artificial cranial deformations) and as a
      ritual. Signs of trepanation have been found in 5% of skulls and 80% of these
      show evidence of the 'patient' having survived such an intervention. Some of them
      have several holes in different stages of healing. The trephining procedure
      involved the use of obsidian knives with wooden handles and tumis, which were
      ceremonial knives that were used to cut the scalp. Gold and silver cranioplasty
      plates have also been found in some skulls. CONCLUSIONS: Cranial trepanation was
      very successful despite the rudimentary methods and instruments employed to
      perform it.

PMID- 15152361
TI  - [The current state of acute intermittent porphyria in the region of Murcia].

PMID- 15152362
TI  - [Bilateral paramedial bulbar infarction secondary to radiotherapy].

PMID- 15152363
TI  - [Neurocryptococcosis in Cuba].

PMID- 15152364
TI  - [The MIDAS questionnaire: disability evaluation in migraine patients].

PMID- 15152365
TI  - [Blink reflex (R3) and facial palsy].

PMID- 15152366
TI  - Prognostic factors in children requiring admission to an intensive care unit
      after hematopoietic stem cell transplant.
AB  - The objectives of this study are to identify prognostic factors of survival to
      discharge in pediatric hematopoietic stem cell transplant (HSCT) recipients
      requiring intensive care unit (ICU) admission, and to determine the utility of
      the Oncological Pediatric Risk of Mortality (O-PRISM) in predicting death of
      these patients. A retrospective cohort of 125 pediatric HSCT recipients from
      October 1992 to September 2002 was analysed to evaluate risk factors of mortality
      in those admitted to ICU after HSCT. Nineteen patients (median age 7.8 years, 14
      boys) required 24 ICU admissions post-HSCT. The most frequent underlying diseases
      were acute myeloid leukemia (n=5). The survival rate on discharge from ICU was
      54%. In univariate analysis, risk factors of mortality included earlier
      requirement of ICU admission post-HSCT (median 34 versus 166 days, p=0.002), a
      longer delay before ICU admission (median 12 versus 5 h, p=0.02), lack of
      neutrophil (p=0.011) or platelet engraftment (p=0.008), macroscopic hemorrhage
      (p<0.001), tachypnoea (p=0.033), hypoxemia (p=0.031), renal impairment (p=0.011),
      coagulopathy (p=0.012), mechanical ventilation (p<0.001), and an increasing
      number of organ failures (p=0.003). Macroscopic hemorrhage and mechanical
      ventilation remained significant in multivariate analysis. Both PRISM and O-PRISM
      scores were significant composite prognosticators. It was concluded that
      mortality of post-HSCT children requiring ICU admission is high, especially in
      those with poor prognosticators.

PMID- 15152367
TI  - Epidemiology of Hodgkin's disease: a review.
AB  - The descriptive and aetiological epidemiology of Hodgkin's Disease (HD) are
      reviewed. Key issues which are highlighted include the evidence suggesting that
      HD is a complex of related conditions that are part mediated by infectious
      diseases, immune deficits and genetic susceptibilities. There is little
      convincing evidence to suggest any other environmental factors are involved in
      the aetiology. The apparent changing pattern of disease by time and from country
      to country, needs careful future study.

PMID- 15152368
TI  - Concentration of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute
      lymphoblastic leukemia after cessation of chemotherapy.
AB  - The immunosuppressive effect of cytotoxic drugs, basic therapeutic agents in the
      treatment of childhood acute leukemias, requires monitoring of the immune system
      following cessation of therapy. The cytokines are soluble proteins that play a
      key role in the immunoregulation of the lymphocyte function. The cytokines
      regulate growth, differentiation and function of various cells in normal
      conditions. The aim of our study was to estimate serum levels of IL-2, IL-6, IL
      8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia (ALL) after
      cessation of chemotherapy. The study involved 150 children with ALL. This group
      consisted of: 30 children 1 month after treatment cessation; 30 children, 3
      months later; 30 children 6 months later; 30 children, 9 months later and 30
      children, 12 months later. The control group consisted of 30 healthy children.
      The levels of the cytokines under study were assayed using the immunoassay kits
      (R&D Systems, USA). During the study significant differences in TNF-alpha, IL-2
      and IL-8 serum concentrations were observed among treated children and controls.
      However there were no differences in IL-6 and IL-10 concentrations.

PMID- 15152369
TI  - Diet, foraging, and use of space in wild golden-headed lion tamarins.
AB  - Lion tamarins (Callitrichidae: Leontopithecus) are small frugi-faunivores that
      defend large home ranges. We describe results from the first long-term
      investigation of wild golden-headed lion tamarins (L. chrysomelas; GHLTs). We
      present data about activity budgets, daily activity cycles, diet, daily path
      length, home range size, home range overlap, and territorial encounters for three
      groups of GHLTs that were studied for 1.5-2.5 years in Una Biological Reserve,
      Bahia State, Brazil, an area characterized by aseasonal rainfall. We compare our
      results to those from other studies of lion tamarins to identify factors that may
      influence foraging and ranging patterns in this genus. Ripe fruit, nectar,
      insects, and small vertebrates were the primary components of the GHLT diet, and
      gums were rarely eaten. Fruit comprised the majority of plant feeding bouts, and
      the GHLTs ate at least 79 different species of plants from 32 families. The most
      common foraging sites for animal prey were epiphytic bromeliads. The GHLTs
      defended large home ranges averaging 123 ha, but showed strong affinities for
      core areas, spending 50% of their time in approximately 11% of their home range.
      Encounters with neighboring groups averaged two encounters every 9 days, and they
      were always aggressive. Data about time budgets and daily activity cycles reveal
      that the GHLTs spent most of their time foraging for resources or traveling
      between foraging sites distributed throughout their home ranges. The GHLTs spent
      much less time consuming exudates compared to lion tamarins in more seasonal
      environments. Additionally, the GHLTs had much larger home ranges than golden
      lion tamarins (L. rosalia), and did not engage in territorial encounters as
      frequently as L. rosalia. GHLT ranging patterns appear to be strongly influenced
      by resource acquisition and, to a lesser extent, by resource defense.

PMID- 15152370
TI  - Validation of urinary cortisol as an indicator of hypothalamic-pituitary-adrenal
      function in the bearded emperor tamarin (Saguinus imperator subgrisescens).
AB  - The use of cortisol levels as a measure of stress is often complicated by the use
      of invasive techniques that may increase hypothalamic-pituitary-adrenal (HPA)
      axis activity during sample collection. The goal of this study was to collect
      samples noninvasively and validate an enzyme-immunoassay (EIA) for the
      measurement of cortisol in urine to quantify HPA axis activity in the bearded
      emperor tamarin (Saguinus imperator subgrisescens). Urine samples were collected
      from trained subjects between 0700 and 0730 hr during a 1-month period, and were
      pooled for immunological validation. We validated the assay immunologically by
      demonstrating specificity, accuracy, precision, and sensitivity. For biological
      validation of the assay, we showed that levels of urinary cortisol (in samples
      collected between 0700 and 1700 hr) varied significantly across the day. Cortisol
      concentration was lowest at 0700 hr, increased to a mid-morning peak (0900 hr),
      and declined across the remainder of the day in a typical mammalian circadian
      pattern. We thus demonstrate that urinary cortisol can be used to quantify HPA
      activity in S.i. subgrisescens.

PMID- 15152371
TI  - Ovarian cycle phase and same-sex mating behavior in Japanese macaque females.
AB  - The relationship of the ovarian cycle phase to same-sex mounting activity in
      adult female Japanese macaques (Macaca fuscata) was studied during the 1997/1998
      mating season. Fecal samples were collected from eight female subjects two to
      three times per week and analyzed by enzyme immunoassay for fecal hormone levels.
      Hormone profiles of estrone (E1) and pregnanediol (PdG) were used to separate
      ovarian cycles into three phases: follicular, periovulatory, and luteal. Patterns
      of same-sex and heterosexual mounting behavior in the females were analyzed for
      phase variation during conceptive cycles. Same-sex mounting among female Japanese
      macaques occurred most frequently during the follicular and periovulatory phases
      of the cycle, and not at all during the luteal phase, paralleling the pattern
      found in heterosexual mounting behavior. These findings suggest a link between
      hormonal fluctuations and patterns of sexual mounting, regardless of whether the
      partner is of the same or opposite sex.

PMID- 15152372
TI  - Sustainability of medical imaging: proposed licensing system and consent
      procedure are impractical.

PMID- 15152373
TI  - Whispered voice test for screening hearing impairment in adults and children:
      systematic review.

PMID- 15152374
TI  - Timing of initial cereal exposure in infancy and risk of islet autoimmunity.

PMID- 15152375
TI  - [Research as permanent education tool].

PMID- 15152376
TI  - [Community participation as a strategy of hypertension control in a health
      district of Ecuador].
AB  - The results of a program for the treatment and control of arterial hypertension
      in a rural community of the northern area of Ecuador are reported through the
      voices and the posters used for patients education, by nurses and health
      promoters (non professional representatives of the community, with a nursing
      role) of the district. The steps of the program, from the awareness of the
      problem because of its high impact on mortality; to the organization of the
      screening for hypertension of 4284 adults (half of the local adult population);
      to the systematic collection of data on mortality are described. One of the
      strategies adopted is the discussion of patients' stories with the local
      communities: the death of a young patient who refused the treatment and died had
      a strong influence in convincing at risk patients to enter the program.
      Treatments were available for 1 dollar a month. Nurses and community health
      promoters have a pivotal role in guaranteeing pressure control and in identifying
      at risk patients with the help of community adapted risk tables. From the
      analysis of data of the first 18 months of follow-up some improvements can be
      observed: grade II hypertensive patients shifted from 34% to 25%; grade III from
      35% to 29%. Lack of compliance with the drug therapy is still one of the main
      problems.

PMID- 15152377
TI  - [Prevention and control of respiratory tract infections in the network of Italian
      Centers for Cystic Fibrosis].
AB  - Infections caused by respiratory pathogens such as Burkholderia cepacia and
      Pseudomonas aeruginosa are associated with an increased morbidity and mortality
      in people affected by cystic fibrosis, the most common lethal genetic disease in
      Caucasian populations. Preventing the acquisition of these pathogens is paramount
      for these patients. The goal of this survey was to assess the distribution and
      the prevalence of the measures adopted for the prevention and control of
      infections caused by respiratory pathogens in the 28 italian centres for cystic
      fibrosis. 21 questionnaires were returned and some important differences can be
      observed in the adoption of segregation measures. Although results may be
      influenced by other factors, specific segregation policies appear to be more
      directly associated than other measures (e.g., intensive disinfection;
      behavioural rules to minimise patient' contacts) with lower prevalence of
      Pseudomonas aeruginosa (OR 0.36 CI95% 0.31-0.42), of multidrug-resistant
      Pseudomonas aeruginosa (OR 0.30 CI95% 0.22-0.40), and of methicillin-resistant
      Staphylococcus aureus (OR 0.67 CI95% 0.48-0.94).

PMID- 15152378
TI  - [Educational activities for the prevention of diabetic foot: foot complications
      at the Center for Diabetes of Rovigo].
AB  - Diabetic patients with neuropathic or vascular foot ulcers are described and
      stratified according to their background risk profiles, as these relate to
      socioeconomic, behavioural and clinical variables. Of the 464 patients admitted
      to the foot clinic between January 2000 and December 2001 only 39% had been
      involved in educational activities for diabetic foot prevention. Seventy-five
      percent of the patients experienced neurologic problems; 76% socioeconomic risk
      factors, also related to the economical situation (unsuitable shoes, no sessions
      with the pedicure). Among the 112 patients with ulcers relapses, in spite of the
      participation to educational interventions, unsuitable shoes were the most
      frequently reported precipitating factor. Larger samples and prospective
      multicentre studies are required to assess the possible yield of educational
      interventions aiming at controlling the care burden and at avoiding the risk of
      major amputations.

PMID- 15152379
TI  - [Epidemiology of caring problems and drug surveillance in the elderly: a
      cooperative development of research protocol].
AB  - Nurses care for elderly patients at home and in nursing homes but there is lack
      of data on the caring problems encountered, their causes and the solutions
      adopted. The aim of the study is to produce the epidemiology of such problems
      and, at the same time, focus nurses' attention on their causes and avoidability.
      The process of definition of caring problems (the focus of the study) and the
      discussion that brought to the draft protocol are described. The final protocol
      (presented with the data collection forms) is articulated in two phases: a
      prevalence survey through a random sampling of points estimates in index days
      over 6 months; a prospective registry over the same period of time of all causes
      perceived as clinically relevant by the nursing personnel, who will document the
      suspected risk factors and causes (including specifically drug therapy), and the
      interventions and measures which are activated.

PMID- 15152380
TI  - [Perception as an area of research].

PMID- 15152381
TI  - [Accidental extubation in intensive care units: what implications for nursing
      care?].
AB  - Unplanned extubations are defined as unwelcome extubations. The phenomenon is
      classified in "accidental extubation", if occurring during procedures performed
      by healthcare workers, or in "self extubation", if the patient removes the
      endotracheal tube. Unplanned extubations are increasingly being considered an
      indicator of healthcare quality in ICU. Their rate varies from 3% to 14% of the
      intensive care units patients, the highest percentages being in burn units (27%).
      Re-intubations rate varies from 31% to 74%, determining increased length of
      hospitalisations without affecting mortality rates. Analysis of the local setting
      is required to improve the safety and quality of care, in order to plan
      appropriate measures, such as staff education. Preventive strategies include:
      increasing safety during nursing interventions, research for risk indicators of
      self-extubation, patient's comfort and sedation protocols, and finally
      alternative methods to physical and pharmacological restraints. The relationship
      between unplanned extubations and nursing workload can be used as indicator for
      the optimization of staff resources in intensive care unit.

PMID- 15152383
TI  - [Epidemiology: from discipline of experts to shared culture].

PMID- 15152382
TI  - [Epidemics of cardiovascular diseases in developing countries].

PMID- 15152384
TI  - Clinical anatomy of the pelvic floor.
AB  - The study presented here comparing cross-sectional anatomy of the fetal and the
      adult pelvic connective tissue with the results of modern imaging techniques and
      actual surgical techniques shows that the classical concepts concerning the
      subdivision of the pelvic connective tissue and muscles need to be revised.
      According to clinical requirements, the subdivision of the pelvic cavity into
      anterior, posterior, and middle compartments is feasible. Predominating
      connecting tissue structures within the different compartments are: Paravisceral
      fat pad within the anterior compartment (Fig. 17, I), rectal adventitia or
      perirectal tissue within the posterior compartment (Fig. 17, II), and uterosacral
      ligaments within the middle compartment. The nerve-vessel guiding plate can be
      found in all of these compartments; it starts within the posterior compartment
      and it ends within the anterior one. It constitutes the morphological border
      between the anterior and posterior compartments in the male. This border is
      supplied by the uterosacral ligaments in the female. Whereas in gross anatomy no
      further border is discernable between anterior and posterior or middle
      compartment, the rectal fascia (hardly visible in embalmed cadavers) demarcates
      the rectal adventitia and is one of the most important pelvic structures for the
      surgeon. In principle, the outlined subdivision of the pelvic connective tissue
      is identical in the male and in the female; facts that become clear from early
      human life and that are already established during this period (Fig. 18). The
      uterus is interposed between the bladder and rectum and subdivides the pelvic
      peritoneum into two pouches thus establishing the only real difference between
      male and female pelvic cavity. The preferential direction of the pelvic
      connective tissue fibers is not changed by the interposition of the uterovaginal
      complex. The pelvic floor muscles are composed of the portions of the levator ani
      muscle, the muscles of the cavernous organs and the deep transverse perineal
      muscle in the male. The latter does not exist in the female. We have clearly
      shown that the different muscles can already be found in early human life and
      that they are never intermingled with the muscular walls of the pelvic organs.
      The levator ani muscle of the female, however, is intermingled with connective
      tissue long before the female sexual hormones exert influence. We have also shown
      that the distinct sexual differences within the pelvic floor muscles as well as
      within the sphincter muscles can already be found in early human life. Both the
      external urethral and the external anal sphincter muscles are not completely
      circular. The external anal sphincter is intimately connected with the internal
      sphincter as well as with the longitudinal muscle. Whereas the innervation and
      function of the urethral sphincter muscles are mostly clear, cloacal development,
      innervation, and function of all parts of anal sphincter complex are not
      completely clarified. As to the support of the pelvic viscera, we believe that
      intact pelvic floor muscles, an undisturbed topography of the pelvic organs, and
      an undisturbed perineum are of more importance than the so-called pelvic
      ligaments. Our hypothesis points to the fact that the support of pelvic viscera
      is multistructural. Thus in pelvic surgery, a lot of techniques have to be
      revised with the aim to preserve or to reconstruct all the structures mentioned.
      This is a multidisciplinary task that can only be solved by cooperation of
      morphologists, urologists, gynecologists, and coloproctologic surgeons or by
      creating a multidisciplinary pelvic floor specialist.

PMID- 15152385
TI  - [Treatment of asthma in children: more than merely 'puffing'].
AB  - Five children, four boys aged 6, 9, 12 and 13 years and one girl aged 6 years,
      had persistent asthmatic symptoms despite maintenance treatment with inhaled
      corticosteroids and short-acting bronchodilators on demand. One of them required
      the addition of a long-acting beta 2-agonist to become symptom-free. The other
      four patients did not need to step up their asthma medication after correction of
      poor inhaler technique, treatment of dysfunctional breathing, treatment of
      allergic rhinitis, and elimination of passive cigarette-smoke exposure,
      respectively. All current guidelines on the treatment of asthma in children
      advise, in case of persistent asthmatic symptoms despite inhaled corticosteroids
      and short-acting bronchodilators, the addition of long-acting beta 2-agonists.
      However, various factors may play a role in the persistence of asthma despite
      adequate therapy and these factors should be evaluated before stepping up the
      medication.

PMID- 15152386
TI  - [Recently published European and American guidelines for the diagnosis and
      treatment of hypertension].
AB  - The European Society of Hypertension in conjunction with the European Society of
      Cardiology has published new guidelines on the management of hypertension. At
      about the same time, the Joint National Committee in the United States updated
      the American hypertension guidelines. Both guidelines agree on a number of
      issues, such as the importance of systolic blood pressure, the necessity to take
      into account additional risk factors and the growing emphasis on combination
      treatment. As far as pharmacotherapy is concerned, however, there are major
      differences between the guidelines. Whereas the European report permits a choice
      from among several classes of drugs for initial treatment, the American
      guidelines still consider diuretics to be the first choice.

PMID- 15152387
TI  - [Dutch Health Council advice 'Vaccination against pneumococcal infections in
      elderly persons and immunocompromised adults'].
AB  - The Dutch Health Council recently reported on the scientific desirability of
      making pneumococcal vaccination available to elderly persons and
      immunocompromised adults. On the basis of an assessment of the scientific
      evidence undertaken by the Dutch Cochrane Centre, the Council has concluded that
      extension of the current indication for pneumococcal vaccination is not
      scientifically justified. Vaccination is definitely recommended only for patients
      suffering from asplenia, sickle-cell anaemia or cerebrospinal fluid leakage.
      Whereas vaccination should be considered in individuals with certain other
      illnesses, vaccination is not recommended for people of advanced age or those
      diagnosed with solid tumours, diabetes mellitus, chronic respiratory disease or
      chronic heart failure.

PMID- 15152388
TI  - [Adjuvant chemotherapy in patients operated on for early ovarian carcinoma].
AB  - The desirability of adjuvant chemotherapy in patients with early ovarian
      carcinoma, i.e. a carcinoma limited to the internal genitalia (FIGO stage I-IIA),
      has long been controversial. Until recently, the few randomised studies that had
      been performed showed no improvement in survival after adjuvant chemotherapy, but
      the numbers of patients were too low to yield convincing proof. Complete surgical
      staging in patients with early ovarian carcinoma is of utmost importance to
      define the stage of the disease. In case of inadequate staging, there is a 24%
      risk (range 16-46%) that undetected tumour deposits will remain in the abdominal
      cavity following surgery, so that the estimated stage will be too low. The
      combined results of the two largest randomised clinical trials on early ovarian
      carcinoma to date have recently been published: the 'Adjuvant chemotherapy in
      ovarian neoplasm' (ACTION) trial, coordinated by the European Organisation for
      Research and Treatment of Cancer (EORTC), and the 'International collaboration in
      ovarian neoplasm' (ICON-1) trial; they showed a significant benefit from adjuvant
      chemotherapy on overall and progression-free survival in early ovarian cancer.
      The ACTION trial (448 patients), however, also showed that adjuvant chemotherapy
      only improved the overall and disease-free survival significantly in inadequately
      staged patients. In the patients who had undergone optimal surgical staging,
      adjuvant chemotherapy had no effect on the prognosis. In the ICON-1 study (477
      patients) there was a favourable effect of adjuvant chemotherapy in the whole
      population. Analysis of this trial, however, shows that most probably only a very
      small percentage of these patients had undergone optimal surgical staging. Based
      on the published results, the best policy for the treatment of patients with
      early ovarian cancer is felt to be to make every effort to achieve optimal
      surgical staging and to reserve the burdensome adjuvant chemotherapy for those
      patients in whom optimal (re)staging is not feasible.

PMID- 15152389
TI  - [Vancomycin resistant enterococci in the Netherlands].
AB  - Enterococci (Enterococcus faecalis and Enterococcus faecium) are relatively
      avirulent enteric bacteria that usually only cause infections in
      immunocompromised patients. Antimicrobial treatment, however, is hampered as
      enterococci are intrinsically resistant to many antibiotics. For years,
      vancomycin was considered the last available antibiotic. Plasmid-mediated
      resistance against vancomycin among enterococci was first described in the
      nineteen-eighties and since then incidences of infection caused by vancomycin
      resistant enterococci (VRE) have increased dramatically, especially in the United
      States. In 2000, three outbreaks of VRE occurred in hospitals in the Netherlands
      and a set of infection-control measures was proposed to limit further
      transmission. These measures were based on the simultaneous isolation of VRE from
      multiple patients. All three outbreaks were controlled by these measures and no
      new outbreaks in Dutch hospitals have been reported since then. Epidemiological
      studies have shown that hospital outbreaks on three continents were caused by a
      subpopulation of E. faecium, which is characterized by the presence of a
      potential virulence gene (variant esp) and resistance to amoxicillin. This
      'hospital strain' of E. faecium has probably been prevalent within hospital
      settings for some time, but only became clinically relevant when it had acquired
      vancomycin-resistance. Current advice is to implement the set of infection
      control measures formulated in 2000, only in those patients colonized by
      amoxicillin-resistant VRE. The potential dangers of VRE were recently underlined
      by the proven transmission of the vancomycin-resistance gene from VRE to
      methicillin-resistant Staphylococcus aureus (MRSA) in two patients in the United
      States. It is in the interest of the patients that prevalence of VRE and MRSA in
      Dutch hospitals should be kept as low as possible.

PMID- 15152390
TI  - [Diagnostic image (187) A teenager in shock three weeks after a gunshot injury.
      Bleeding from a delayed renal artery pseudoaneurysm].
AB  - A 15-year-old boy was hospitalised because of injuries caused by a gunshot. After
      three weeks shock developed due to bleeding from a renal artery pseudoaneurysm.

PMID- 15152391
TI  - [Important prognostic significance of a sentinel-node biopsy in patients with
      malignant melanoma].
AB  - OBJECTIVE: To determine the prognostic significance of sentinel-node biopsy in
      patients with malignant melanoma (unlike the United States, a sentinel-node
      biopsy is still not routinely performed on melanoma patients in the Netherlands,
      as the outcomes of prospectively randomised clinical trials are being awaited).
      DESIGN: Retrospective. METHODS: Between 1996 and 2001 a sentinel-node biopsy and
      a re-excision of the scar of the diagnostic biopsy were performed on all melanoma
      patients who had a Breslow thickness > or = 1 mm or a Clark level > or = IV. At
      operation the sentinel node was identified with a gamma probe and patent blue. It
      was removed and sent for pathological investigation for the presence of melanoma
      cells. If the sentinel node was tumour positive, a dissection of the regional
      lymph-node basin was performed. Subsequently, these patients were put forward for
      the European Organisation for Research and Treatment of Cancer (EORTC)
      peginterferon alfa(2b) adjuvant treatment study. RESULTS: A sentinel-node biopsy
      was performed in 61 lymphnode basins in 57 patients (18 male and 39 female;
      median age: 45 years (range: 9-80)). The median Breslow thickness of the
      melanomas was 2.2 mm (range: 0.7-13 mm). In 10 of the 61 cases histological
      examination of the sentinel node demonstrated tumour cells. In 2 additional cases
      tumour cells were demonstrated only by immunohistochemical studies or complete
      dissection of the node. Eight regional lymph-node basins were dissected, two of
      which contained additional metastases. The median follow-up was 36 months (range:
      1-68). During follow-up 12 of the 57 patients were found to have metastases, in 8
      of these patients the sentinel-node biopsy contained tumour cells. The negative
      predictive value of a tumourless sentinel node with respect to the later
      occurrence of distant metastases was 92%. CONCLUSION: The patients with a tumour
      positive sentinel node had a poorer prognosis with respect to distant metastases
      than patients with a tumour-negative node. This is the main reason for performing
      sentinel-node biopsy: to predict the prognosis of the disease. Therefore sentinel
      node biopsy should be incorporated into the treatment of patients with malignant
      melanoma.

PMID- 15152392
TI  - [Allergy testing possibly useful in children less than 4 years of age with
      recurrent cough and wheeze].
AB  - OBJECTIVE: To assess the diagnostic value of measuring allergen-specific IgE
      antibodies in children less than 4 years of age with recurrent cough and wheeze.
      DESIGN: Retrospective cohort study. METHOD: The prevalence of specific
      sensitisation for inhaled and food allergens that can be demonstrated by means of
      Phadiatop and enzymatic assays was determined on the basis of clinical data on 97
      children under four years of age that had been referred to a paediatrician for
      recurrent cough and wheeze. RESULTS: Measurement of allergen-specific IgE
      antibodies was performed in 44 (45%) of the 97 patients (58 boys and 39 girls;
      median age: 13 months). Sensitisation was demonstrated in 15 of 44 patients
      (34%). Children who were three years old or older or who had eczema or rhinitis
      apart from colds had a statistically significantly higher chance of having
      specific antibodies than children who were younger or who did not have these
      symptoms. CONCLUSION: Measurement of allergen-specific IgE antibodies can also
      reveal sensitisation in young children with recurrent cough and wheeze. The
      likelihood of finding specific antibodies was higher in children in whom either
      the history or the physical examination revealed indications of eczema or
      rhinitis apart from colds.

PMID- 15152393
TI  - [Persistent fever of unknown origin in two young infants caused by the atypical
      form of Kawasaki disease].
AB  - Two previously healthy infants, a boy and a girl aged 3 and 4 months,
      respectively, were admitted for fever of unknown origin with laboratory results
      indicating an inflammation. The boy presented with vomiting, pyuria, anaemia, and
      thrombocytosis. The girl presented with irritability, erythema and diarrhoea. All
      viral and bacterial cultures remained negative and supplementary radiology was
      unable to detect a focus of infection. The fever had persisted for at least 12
      days in both cases before the diagnosis 'atypical Kawasaki disease' was
      considered. Cardiac echograms showed dilatation of the coronary arteries in both
      patients and confirmed the diagnosis. Immediate therapy with intravenous
      immunoglobulins and acetylsalicylic acid was given, whereupon the fever subsided
      within 24 hours; the further clinical course was uneventful. These cases
      illustrate the fact that atypical Kawasaki disease is often a late consideration,
      especially when the symptoms of the classical form are absent. This condition
      should be considered in every infant presenting with long-lasting unexplained
      fever.

PMID- 15152394
TI  - [A patient with a palpable nodule in the throat due to a cystic parathyroid
      adenoma].
AB  - In a 38-year-old woman who was examined because of an otherwise asymptomatic
      palpable nodule in the thyroid region, a cystic parathyroid adenoma was
      diagnosed. The aspirate was clear with a slight yellowish colour and a very high
      parathormone concentration. The serum-calcium concentration was also very high.
      The lesion was surgically removed. The surgical specimen contained a parathyroid
      adenoma with pseudocystic degenerative changes. The patient recovered fully.

PMID- 15152395
TI  - [Obstructive azoospermia in men who wish to father children; diagnosis and
      surgical sperm retrieval].

PMID- 15152396
TI  - [Obstructive azoospermia in men who wish to father children; diagnosis and
      surgical sperm retrieval].

PMID- 15152397
TI  - [Obstructive azoospermia in men who wish to father children; diagnosis and
      surgical sperm retrieval].

PMID- 15152398
TI  - [The biopsying of at least 5 mediastinal lymph node stations for presurgical
      staging in patients with a non-small-cell lung carcinoma].

PMID- 15152399
TI  - [Prophylactic perioperative beta-blockade reduces cardiac morbidity and mortality
      following non-cardiac surgery in patients at risk].

PMID- 15152400
TI  - Reducing the heavy burden of obesity.

PMID- 15152401
TI  - Patient choice in renal care.

PMID- 15152402
TI  - Partnerships will get the best result.

PMID- 15152403
TI  - Listening to voices of experience.

PMID- 15152404
TI  - The counterweight programme: tackling obesity in primary care.
AB  - Practice nurses are ideally placed to tackle obesity and reduce its impact on
      health and NHS finances--but to give patients the right support, they need
      appropriate training, materials and support themselves. A programme being tested
      in various practices across the UK is providing this, with positive results. This
      paper looks at progress made in one practice.

PMID- 15152406
TI  - Choice and use of peripherally inserted central catheters by nurses.
AB  - Patients requiring i.v. treatment of between six weeks and six months will
      benefit from having a peripheral or central i.v. line. PICCs have a number of
      advantages over other peripheral or central devices. There is less risk of
      complications and infection than with central devices and repeated venepunctures
      are avoided as one PICC should provide adequate access throughout.

PMID- 15152405
TI  - Current options for managing the problem of excess wound exudate.
AB  - Excess exudate is one of the most difficult aspects of wound management. It can
      be extremely distressing to patients and can result in heavy, leaking dressings,
      soiled clothing and bedding, and damage to surrounding skin. This paper provides
      practical guidance on the products and techniques currently available and how to
      tailor them to the needs of individual patients.

PMID- 15152407
TI  - User involvement in care: avoiding tokenism and achieving partnership.
AB  - Public involvement in health care has increased in recent years, and patients now
      expect to have greater input into the care and services they receive. This paper
      describes an initiative in one trust in which patients with cancer were able to
      take a lead in improving services. The evolution of the group into a cancer
      patients' forum offers an example of good practice.

PMID- 15152408
TI  - The causes of cancer-related fatigue and approaches to its treatment.
AB  - Despite the evidence that patients with cancer experience fatigue as a symptom of
      their condition or as a consequence of treatment, there is no uniform definition
      of the term, making it difficult to identify the causes. Patients also lack
      professional support to help them cope. This paper describes the potential causes
      of fatigue and provides some management solutions.

PMID- 15152409
TI  - Using process mapping to improve nursing practice and patient care.
AB  - Process mapping is a technique that models the relationship between activities,
      people and resources. It is used to develop a better understanding of the
      patient's experience and to drive forward service modernization. This paper
      offers a brief guide to process mapping and examines the potential impact it may
      have on nursing services and patient care.

PMID- 15152411
TI  - Intermittent catheterisation in school: a collaborative agreement.
AB  - Enabling children with medical needs to attend mainstream education can be a
      challenge for parents, teachers and health-care professionals. A lack of national
      standards on the management of continence in schools results in enormous
      variations in practice. This paper describes a collaborative approach to address
      the issues in schools in Manchester.

PMID- 15152410
TI  - Catheter-associated UTIs in patients after major gynaecological surgery.
AB  - A group of nurses undertook an audit across two hospitals comparing the incidence
      of catheter-related urinary tract infections in patients who had catheters
      inserted during major gynaecological surgery. The data suggests that using an
      anaesthetic lubricating gel for catheterisation reduces urinary tract infection
      rates for these patients.

PMID- 15152412
TI  - Through the patient's eyes.

PMID- 15152413
TI  - Neurorehabilitation nursing research behind bars: the lived experience.

PMID- 15152414
TI  - How do we ethically manage patients who refuse therapy?

PMID- 15152415
TI  - Crossing professional boundaries: ethical, legal and case perspectives.

PMID- 15152416
TI  - Incorporating foot care education into diabetic foot screening.
AB  - Rehabilitation nurses care for patients with diabetes who have strokes,
      orthopedic surgery, and spinal cord injuries; therefore, they should be
      knowledgeable about foot screening technique and foot care education so that they
      can identify patients who are at risk for foot skin breakdown. The objectives of
      diabetic foot screening are to identify foot problems, determine a foot risk
      category and management category for patients, and to instruct patients with
      diabetes and their families in proper foot care. The screening technique is
      simple and can be used in clinic settings or at the bedside. Incorporating foot
      care education into the foot screening process increases or reinforces patients'
      knowledge of self-care. Such knowledge empowers patients to join with their
      healthcare teams to decrease the incidence of ulceration and amputation.

PMID- 15152417
TI  - The use of aesthetic knowledge in the management of brain injury patients.
AB  - A patient's recovery from a brain injury (BI) is unpredictable and requires
      flexible nursing strategies for each stage of recovery. Empirical knowledge
      provides a framework for delivering nursing care based on scientific principles.
      Aesthetic knowledge, including intuition, provides a further opportunity to know
      and understand BI patients and their responses as they progress along the
      trajectory of recovery. Incorporating both empirical and aesthetic knowledge into
      the nursing plan of care for this population affords on opportunity for nurses to
      help patients and their families negotiate the course of recovery with greater
      success.

PMID- 15152418
TI  - Optimizing the functionality of clients with age-related macular degeneration.
AB  - Age-related macular degeneration (ARMD) is a major cause of severe vision loss
      and blindness among older people. This condition is progressive, incurable, and
      significantly compromises central vision. Rehabilitation nurses have a pivotal
      role in the assessment and management of clients with ARMD. An understanding of
      incidence and pathophysiology of ARMD, as well as health promotion and a new
      treatment for ARMD can help rehabilitation nurses design interventions to help
      clients maintain an acceptable quality of life despite declining vision.

PMID- 15152419
TI  - Internet-based support for rural caregivers of persons with stroke shows promise.
AB  - The purpose of this pilot study was to test the feasibility of providing Internet
      based education and support intervention to caregivers living in rural settings,
      including caregivers' satisfaction with the intervention. A secondary aim was to
      explore their experience of caring. Nine adult caregivers of persons with stroke
      were enrolled in this descriptive study from rehabilitation centers in
      northwestern Ohio and southeastern Michigan. They were given access to the
      intervention, Caring-Web, for three months. Data were collected from
      participants' bimonthly interviews, as well as e-mail communications. Procedures
      were tested and found valid, and caregivers were willing and able to use Caring
      Web. Using Friedemann's framework of systemic organization, a coding system was
      developed for analyzing the qualitative data on the experience of caring. Five
      main themes emerged from these data. These findings help expand knowledge about
      caregivers dealing with stroke.

PMID- 15152420
TI  - Management of adult patients with a left ventricular assist device.
AB  - The number of left ventricular assist device (LVAD) implantations is growing as a
      result of increased waiting periods for cardiac transplantation and the decreased
      availability of organ donors. Furthermore, the Food and Drug Administration (FDA)
      has approved permanent LVAD support. After an acute hospitalization, patients
      with LVADs may need prolonged convalescence in a healthcare facility because they
      have complex medical needs and are physically disabled. Admission criteria need
      to be developed as essential patient and nursing competencies need to be defined
      as a part of a successful LVAD program in an acute rehabilitation center. Acute
      rehabilitation centers can help patients with LVADs transition to a home setting.

PMID- 15152421
TI  - Introduction. Evolution, prevention, and responses to aggressive behavior and
      violence.

PMID- 15152422
TI  - Evolutionary ethics, aggression, and violence: lessons from primate research.

PMID- 15152423
TI  - Is there value in identifying individual genetic predispositions to violence?

PMID- 15152424
TI  - Firearms, violence, and the potential impact of firearms control.

PMID- 15152425
TI  - The production of criminal violence in America: is strict gun control the
      solution?

PMID- 15152426
TI  - Controlling communications that teach or demonstrate violence: "the movie made
      them do it".

PMID- 15152428
TI  - Interpersonal violence and public policy: what about the victims?

PMID- 15152427
TI  - Preventive confinement of dangerous offenders.

PMID- 15152429
TI  - Strengthening the collaboration between public health and criminal justice to
      prevent violence.

PMID- 15152430
TI  - Why not retribution? The particularized imagination and justice for pregnant
      addicts.

PMID- 15152431
TI  - Ending concerns about undue inducement.

PMID- 15152432
TI  - Natural settings trials--improving the introduction of clinical genetic tests.
AB  - Approaches to genetic testing differ in the research setting and the clinical
      setting. More data are needed to develop approaches that will best facilitate the
      use of new genetic tests in the clinical setting, especially settings where
      genetic testing has not been widely used, such as in primary care. Furthermore,
      data are needed to establish the clinical utility of new genetic tests in the
      general practice setting. Natural setting trials are proposed as a strategy to
      develop this information. While natural setting trials are clinical research
      studies and will expose participants to some degree of risk, the risks are
      different, and arguably less than the risks those same individuals would
      otherwise face if the test went directly into clinical practice. Ultimately,
      clinical practice and safety of new genetic tests can be improved by adding the
      evaluation provided by natural setting trials.

PMID- 15152433
TI  - Research ethics and misguided moral intuition.

PMID- 15152434
TI  - Legal enforcement of xenotransplantation public health safeguards.

PMID- 15152435
TI  - Evaluation of the condom distribution program in New South Wales Prisons,
      Australia.

PMID- 15152436
TI  - Benign neglect or neglected abuse: drug and alcohol withdrawal in U.S. jails.

PMID- 15152437
TI  - Legal barriers to implementing recommendations for universal, routine prenatal
      HIV testing.

PMID- 15152438
TI  - Confounding extremities: surgery at the medico-ethical limits of self
      modification.

PMID- 15152439
TI  - Political authority in a bioterror emergency.

PMID- 15152441
TI  - Courts protect Ninth Circuit doctors who recommend medical marijuana use.

PMID- 15152440
TI  - A human germline modification scale.

PMID- 15152442
TI  - Cigna settles with health care providers.

PMID- 15152443
TI  - The Eleventh Circuit holds that agreements in which pharmaceutical companies pay
      generic companies not to compete may be valid.

PMID- 15152444
TI  - FDA to ban sales of dietary supplements containing ephedra.

PMID- 15152445
TI  - Advances in the management of localized breast cancer: an overview.
AB  - Over the last few decades, there have been unprecedented advances in the
      multidisciplinary management of breast cancer. Surgical principles have shifted
      away from the Halstedian concept of radical surgery towards more cosmetic breast
      conserving procedures, and advances have been made in terms of oncologic and
      plastic surgical techniques for those opting for mastectomy and reconstruction.
      Sentinel lymph node biopsy has revolutionized the evaluation of patients' nodal
      status and has become widely accepted as "state of the art." Medical oncology has
      made tremendous advances and is no longer relegated to the patients with
      metastatic disease. It is well accepted that chemotherapy may play a role even in
      patients with small tumors. Certainly the impact of neoadjuvant chemotherapy for
      downsizing tumors and making them amenable for breast conservation is also widely
      accepted. The advent of anthracyclines and, more recently, taxane-based regimens
      has had a substantial impact on the management of breast cancer. In addition,
      newer hormonal therapies such as the aromatase inhibitors have rivaled the
      classic cornerstone of tamoxifen. Radiation therapy has evolved from the era of
      cobalt-based therapy to newer, less morbid, techniques. In addition to advances
      in external beam radiation, the concept of accelerated partial breast irradiation
      and intraoperative radiation therapy is evolving and continues to be the focus of
      research endeavors. The unparalleled advances in the management of breast cancer
      in the fields of surgical, medical, and radiation oncology over the last half
      century continue today with ongoing research and clinical trials. As we enter the
      new millennium, breast cancer management will continue to evolve.

PMID- 15152446
TI  - Rocky Mountain spotted fever at Koair Children's Hospital, 1990-2002.
AB  - The reported average annual incidence of Rocky Mountain spotted fever (RMSF) in
      Kentucky is less than 5 per million population, although seroprevalence studies
      suggest that exposure to Rickettsia riskettsii, the causative agent, is
      relatively common among children. The experience with RMSF at Kosair Children's
      Hospital over a 12-year period was reviewed. Fifteen cases were identified (5
      boys and 10 girls). Illness onset ranged from April to October, and 4 patients
      resided in Jefferson County. The classic triad of fever, rash, and headache was
      present in only 60% of cases, and tick attachment was reported in only 40%. On
      average, 6 days elapsed from onset of symptoms to initiation of appropriate
      antibiotic therapy. One patient suffered splenic infarction and necrosis of the
      digits due to shock and disseminated intravascular coagulopathy, and 2 patients
      died. RMSF is a significant cause of pediatric morbidity and mortality in this
      region of Kentucky. Affected children may reside in relatively urban parts of the
      state. Initial clinical features may be nonspecific. This, as well as decreased
      awareness of disease and (unjustified) reluctance to use doxycycline may
      contribute to delays in initiating therapy.

PMID- 15152447
TI  - Cerebral intraventricular mass due to cysticercosis: two cases reports.

PMID- 15152448
TI  - Treatment options for opiate addiction.

PMID- 15152449
TI  - Through a glass darkly.

PMID- 15152450
TI  - [Neurology in the 21st century--the era of preventive neurology utilizing new
      diagnostic and therapeutic techniques].
AB  - The aims of neurology in Japan in the 21st Century should include establishment
      of therapeutic measures for neurological diseases, training clinical neurologists
      to cover both static and dynamic aspects of neurology, and application of gene
      therapy and neurogenesis to clinical neurology. It is also important to note that
      once any neurological disease develops, remaining sequelae are usually not
      curable, so the problem of how to prevent the onset of neurological diseases,
      that is preventive neurology, will become increasingly important. The key target
      for prevention in neurology is cerebro-vascular disease, since it is very common.
      Many risk factors are known for ischemic CVD. However, even for the management of
      hypertension, the so-called number needed to treat (NNT) is 29-118/5 years for
      primary prevention and 14-23/5 years for secondary prevention. It is also
      important to consider genetic factors that influence CVD, including abnormal
      plasminogen, Lp (a), ACT Isehara 1 gene, apolipoprotein E and so on, since these
      congenital factors reinforce known acquired risk factors, such as hypertension.
      In addition, the presence of asymptomatic cerebral infarction, as well as PVH and
      DSWMH, in MRI T2-weighted images is an important predictor of future symptomatic
      CVD. Finally, storage of one's own bone marrow cells might be useful, since in
      the event of onset of CVD, dementia or other neurological diseases,
      autotransplantation with cytokine might become available for neurogenesis. The
      results of our recent experiments indicate that this idea may be feasible.

PMID- 15152451
TI  - [Perfusion-CT guided acute stroke management].
AB  - The easily accessible and available PCT reliably identifies reversible and
      irreversible ischaemia in acute stroke patients. These knowledge will allow
      treatment strategies to become more appropriate and individualized. Patients with
      significant penumbra may be candidates for treatment with dangerous or costly
      medication, and patients without may not, independently of duration of stroke
      symptoms. Furthermore, PCT also has the scientific potential to identify
      appropriate patients for therapeutic trials. Finally, salvage of PCT-defined
      penumbra could be used as a surrogate marker for effectiveness of interventions.

PMID- 15152452
TI  - [Changes in neurological diseases during the last half century. Neuropathological
      view point].
AB  - Environmental changes are intensifying at an increasing tempo along with the
      advance of civilization. The appearance change and disappearance of certain
      diseases are remarkable. The author has been studying the neuropathology of fatal
      neurodegenerative diseases endemic to the native Chamorro population on Guam
      during the last half century. During this time, significant advances in
      scientific technology, such as electron microscopy, immunohistochemistry and
      molecular biology has contributed to an impressive development of neuropathology.
      Many new findings have been discovered allowing delineation of additional disease
      entities. In addition, many new neurological disorders have appeared. This
      communication reviews clinicopathology of amyotrophic lateral sclerosis and
      parkinsonism-dementia complex on Guam as well as improvement of the nervous
      system as a complication of AIDS studied at Montefiore Medical Center in New
      York.

PMID- 15152453
TI  - [Visual child neurology].
AB  - In neurodevelopmental disorders, the characteristic symptoms appear age
      dependently along with the functional and morphological development of the
      affected neurons and the neuronal pathways. Most of them have the primary lesion
      in the subcortical structures as these mature earlier, which include the
      aminergic neurons of the brainstem and the midbrain having important roles for
      development of the higher cortical function (HCF). Thus, to clarify the
      pathophysiologies of the symptoms appearing age-dependently makes it possible to
      demonstrate the process of development of the HCF. Here, I reviewed the
      characteristic symptoms and their pathophysiologies of Rett syndrome, DYT-1,
      autosomal dominant GTP cyclohydrolase I (ADGCH I) deficiency, Tourette syndrome
      (TS) and Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH),
      and suggested that the brainstem aminergic neurons modulating the locomotion have
      roles for development of the frontal cortex, the dopaminergic neurons and basal
      ganglia pathways involving in the action dystonia for motor execution and the
      serotonergic and the dopaminergic neurons projectioning to the nonmotor basal
      ganglia thalamocortical circuits for development of the frontal area, the targets
      of the circuits. While, postural dystonia, tics in GTS and symptoms in EAOH
      reflect the development of the causative neurons and the neuronal systems.

PMID- 15152454
TI  - [Neurological aspects in antiphospholipid syndrome].
AB  - Antiphospholipid syndrome is considered to be a cause of an acquired
      hypercoagulable state leading to stroke and transient ischemic attack.
      Antiphospholipid antibodies (aPL) comprise a heterogeneous group of
      autoantibodies. Among them, lupus anticoagulant (LA) and beta 2-glycoprotein I
      dependent anticardiolipin antibody (beta 2-GPI aCL) are important and commonly
      measured. Recently, LA has been considered to be closely related to
      phosphatidylserine anti-prothrombin antibody. APL is an independent risk factor
      for first-ever ischemic stroke and a prognostic marker of recurrent stroke. The
      precipitating factors for the occurrence of stroke are the presence of beta 2-GPI
      dependent aCL, a GPL aCL level of more than 40, and the simultaneous presence of
      lupus anticoagulant. Several mechanisms are believed to be involved in the
      thrombotic process in patients with antiphospholipid antibodies. Human activated
      protein C functions as a potent anticoagulant in human plasma by inhibiting the
      activity of coagulation cofactors Va and VIIIa. Activation of protein C is
      impaired in patients with aPL. Recently, the presence of aPL has been considered
      to be contributory factor for the development of atherosclerotic lesions.
      Transgenic mouse lacking the LDL receptor develop accelerated arteriosclerosis
      upon immunization with beta 2-GPL Several therapeutic options are available for
      the prevention of ischemic stroke in patients with aPL, such as antiplatelet,
      anticoagulant, and immunosuppressive therapy. The rate of recurrence in patients
      undergoing antiplatelet and anticoagulation combination therapy was found to be
      lower than that in patients receiving other forms of therapy. The WARSS-APASS
      collaborative study showed that there was no difference in the recurrence rate
      between aPL patients receiving antiplatelet or anticoagulation therapy alone. APL
      has been investigated in other neurological disorders such as multiple sclerosis,
      chorea, migraine and convulsion. The association of aPL with multiple sclerosis
      remains debatable. APL could be a contributory factor for the development of
      convulsion, but not for migraine.

PMID- 15152455
TI  - [Pitfall in migraine treatment].
AB  - Migraine is a very common disorder. In Japan, an estimated 8.4% of population
      experience migraine, but most of them go undiagnosed and undertreated. Recent
      advances in basic and applied clinical neuroscience have led to the development
      of sumatriptan, a new class of selective serotonin (5-hydroxytryptamine (5-HT))
      receptor agonists that activate 5-HT 1B/1D receptors. Following sumatriptan
      several other triptans were produced. They have three main mechanism of action:
      cranial vasoconstriction, peripheral trigeminal inhibition, and inhibition of
      transmission through second order neurons of the trigeminocervical complex. Even
      in our country, we can now use three kinds of triptans, which are very effective
      medicine against acute migraine with a well-developed scientific rationale.
      Despite the higher price, triptans were preferred over ergots in most patients.
      Recently Limmroth et al reported a prospective study for medication overuse
      headache (MOH) in 98 patients. The mean critical duration until onset of MOH was
      shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for
      analgesics (4.8 years). The mean critical monthly intake frequencies was lowest
      for triptans (18 single doses per month), higher for ergots (37), and highest for
      analgesics (114). We should keep in mind that overuse of triptans leads to MOH
      faster and with lower dosages compared with ergots and analgesics.

PMID- 15152456
TI  - [How to clinically approach involuntary movements].
AB  - Upon clinical examination of involuntary movement, its correct diagnosis and
      classification is most important for choosing its most appropriate treatment.
      Correct diagnosis of involuntary movements should be based on their clinical
      characteristics rather than laboratory data. First attention should be paid to
      the way of its occurrence; whether it repeats itself at a relatively regular
      period or it occurs irregularly. Among irregular movements, chorea and ballism
      (us) belong to the same category clinically as well as neuropharmacologically;
      both respond to benzodiazepine and D2 receptor blockers. Dyskinesia and akathisia
      are often drug-induced. Athetosis often overlaps chorea and dystonia. Dystonia is
      characterized by excessive muscle contraction in terms of strength, spread and
      duration. Recently involvement of the sensori-motor cortex is emphasized in
      generation of focal dystonia. Myoclonus is usually caused by abrupt muscle
      contraction but also by sudden cessation of muscle contraction (negative
      myoclonus). Myoclonus and tics are usually irregular, but they can be rhythmic or
      quasiperiodic. Tremor is often associated with dysfunction of basal ganglia,
      cerebellum or thalamus, but recently an increasing attention has been paid to
      involvement of the sensori-motor cortex. Some involuntary movement could show
      features of two or more kinds of involuntary movements or it may shift among
      different kinds of involuntary movements or among different subgroups of that
      particular involuntary movement. Therefore, it is not advisable to feel obliged
      to classify every single involuntary movement into any pre-existing category.
      Instead a more flexible approach is warranted.

PMID- 15152457
TI  - [Neural damage associated with allergic diseases: pathomechanism and therapy].
AB  - We disclosed the occurrences of myelitis with atopic diathesis preferentially
      affecting the cervical spinal cord in Japan. Recent nationwide survey revealed
      that this condition occurs throughout Japan. The characteristic features are: (1)
      young to middle-aged adults with atopic diathesis are affected, (2) stepwise
      progression and fluctuation of the symptoms are frequent, (3) paresthesia and
      dysesthesia are the initial and predominant symptoms while severe motor weakness
      is rare, (4) CSF abnormalities are infrequent and mild, (5) hyperIgEaemia and
      mite antigen-specific IgE are present in most cases and eosinophilia is present
      in about half cases, (6) cervical spinal cord is affected most frequently by
      clinical symptomatology and on MRI. In this condition, plasma exchange is
      beneficial in about 80% while corticosteroids are effective only in 50%. The
      spinal cord biopsy specimens demonstrated its neuropathology to be eosinophilic
      myelitis involving myelin as well as axon. We also found that Hirayama disease is
      associated with airway allergy such as allergic rhinitis and atopic asthma. In
      children, poliomyelitis-like illness after acute asthma attacks is well known as
      Hopkins syndrome. These findings strongly suggest a link between atopic diathesis
      and spinal cord damage.

PMID- 15152458
TI  - [Cardiopulmonary failure in Duchenne muscular dystrophy--pathophysiology and
      management].
AB  - As there is no cure in patients with Duchenne muscular dystrophy (DMD) yet, we
      must pay attention to manage cardiopulmonary complications in DMD. They died at
      18.2 years old in 1984 in my hospital. From autopsy findings, respiratory failure
      occupied 75%, and left-sided heart failure occupied 12.5%. First of all, we had
      to know the relationship between cardiac system and respiratory system. Right
      sided heart catheterization revealed that respiratory failure patients were
      divided into Forrester's subset 1 (left ventricular function was within normal
      limits). So, it is unnecessary to give digitalis and/or diuretics for patients
      with respiratory failure. They only need respirator treatment. We tried cuirass
      ventilation since 1984. This respirator elongated their lives about 3 years.
      Since 1991 NIPPV was introduced in Japan, this treatment elongated their lives
      about 5.5 years. Nowadays TIPPV with tracheostomy is not first choice of
      treatment but we select this treatment not so unwillingly as before. As for left
      sided heart failure, BNP (brain natriuretic peptide) is now considered useful
      parameter for left ventricular function. Japanese clinical researcher proposed
      treatment based on Values of BNP in left-sided heart failure. In 1980s, from the
      onset of heart failure until death was only 16 months, we feel that better
      results already accomplished. Kawai reported that average age at death in Japan
      was 26.8 years old in 2002. Our efforts must be done more and more until cure of
      this disease can be found.

PMID- 15152459
TI  - [Clinical aspects of abnormal eye movements].
AB  - This paper reviews a variety of abnormal eye movements which include abnormal
      ocular positions, restricted eye motions, impairment of conjugated eye movements,
      abnormal smooth pursuit, abnormal saccade, gaze-evoked nystagmus, down-beat
      nystagmus, internuclear ophthalmoplegia, supranuclear ophthalmoplegia, square
      wave jerks, roving eye movement, ocular bobbing, ocular dipping, reverse ocular
      bobbing, and ping-pong gaze. Abnormal eye movements occur from stroke,
      spinocerebellar degeneration, Parkinson disease, multiple system atrophy,
      progressive supranuclear palsy, multiple sclerosis, Miller Fisher syndrome,
      myasthenia gravis, opsoclonus-polymyoclonia syndrome, and Creutzfeldt-Jakob
      disease. In neurological practice, it is important to observe abnormal eye
      movements accurately and enthusiastically, to make appropriate anatomical and
      etiological diagnosis.

PMID- 15152460
TI  - [Clinical phenotype of Charcot-Marie-Tooth disease (CMT) and familial amyloid
      polyneuropathy (FAP)].
AB  - A nationwide study of CMT and FAP has been performed. In FAP TTR Met30 families
      with late onset, neuropathy showed male preponderance, low penetrance, little
      relationship to endemic foci, sensorimotor symptoms beginning distally in the
      lower extremities with disturbance of both superficial and deep sensation, and
      relatively mild autonomic symptoms, consistent with pathological findings. In
      contrast, families with early onset showed higher penetrance, concentration in
      endemic foci, predominant loss of superficial sensation, severe autonomic
      dysfunction. Demyelinating versus axonal phenotypes are major issues in CMT.
      CMT1A duplication caused mainly demyelinating phenotype, while axonal features
      were variably present. In CMT1B, two distinctive phenotypic subgroups were
      present: one showed exclusively axonal features; and another was exclusively
      demyelinating. CMTX showed intermediate slowing of MCV, predominantly axonal
      features, and relatively mild demyelinating pathology. Differing from CMT1B,
      these axonal and demyelinating features were concomitantly present in individual
      patients in variable extent. Median nerve MCVs were well maintained independently
      of age, disease duration, and severity of clinical and pathologic abnormalities.
      Amplitude of CMAPs was correlated significantly with distal muscle strength,
      indicating that clinical weakness results from reduced numbers of functional
      large axons, not from demyelination. CMT patients with demyelinating and/or
      axonal features, together with FAP patients with axonal feature and scattered
      distribution, are supposed to increase according to the development of genetic
      diagnosis for hereditary neuropathy that verifies late-onset, de novo and
      asymptomatic patients.

PMID- 15152461
TI  - [Familial non-Alzheimer dementia].
AB  - This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular
      dementia 1) Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is characterized by autosomal dominant
      inheritance, smooth muscle cell degeneration and granular osmiophilic material
      (GOM) in arterioles, and Notch 3 mutations. 2) CARASIL This is an autosomal
      recessive vascular dementia with unknown etiology. 3) Familial amyloid angiopathy
      Familial cerebral hemorrhage and dementia is caused by mutations in amyloid
      precursor protein, cystatin c, and Bri genes. 2. Familial non-Alzheimer
      degenerative dementia 1) Dementia with Lewy bodies This is characterized by
      Alzheimer like dementia, visual hallucination and diffuse Lewy bodies which are
      formed by ubiquitinated alpha-synuclein. Occasionally, familial forms are
      reported, but gene mutations are unknown. 2) Frontotemporal dementia (FTD) FTDP
      17 is characterized by tau mutations, character and personal changes, and
      disinhibition. The gene mutations were also found in familial forms of Pick's
      disease, corticobasal degeneration, and other tauopathies. 3) Familial British
      dementia (FBD), familial Danish dementia (FDD) FBD and FDD are characterized by
      Abri amyloid deposits, amyloid angiopathy and dementia. Mutations in Bri gene are
      reported. 4) Familial encephalopathy with neuroserpin inclusion bodies (FENIB)
      FENIB is characterized by dementia, Collins body and neuroserpin gene mutation.

PMID- 15152462
TI  - [Medical care and long-term care insurance and clinical practice guideline for
      neurological disorders].
AB  - Society in 21st century is a global community, and undergoes a paradigm shift to
      a new value. This is about the significance of clinical practice guideline for
      neurological disorders as a new paradigm in information technology society and
      global community. Medical care is required to be "safer, more effective, more
      efficient and more transparent" in 21st century. In order to improve the quality
      of medical care, not only the improvement of the quality in manpower but also the
      betterment of the response to patients based on proper balance between quality
      and efficiency of medicine is required and clinical practice guideline for
      patients and medical doctors should be actively utilized. Guidelines are socially
      positioned following regulations, directives and recommendations and it is not
      restriction upon practitioner and patient decisions about appropriate health
      care. In the definitions of Institute of Medicine and Medline-MeSH, a word
      "assist" is used and it is said that guidelines are "means to realize EBM
      assisting decision making" for medical doctors to expertise their specialties. It
      has a significant meaning in connection with doctors' discretion. When clinical
      practice guidelines clarify the intended purpose and are applied as suggestion
      instead of obligation, they would not invade doctors' discretion.

PMID- 15152463
TI  - [Neurological disease in measures against intractable diseases in Japan].
AB  - Japan has been taking measures to cope with intractable diseases centering on
      five principles: "promoting investigation and research", "providing medical care
      facilities", "reducing co-payment for medical costs", "improving and coordinating
      community-based health care", "medical care and welfare services", and "promoting
      welfare measures aimed at improving the quality of life (QOL)". As the object of
      measures, 118 diseases including serious neurological diseases (e.g. ALS, CJD, PD
      etc.) have been specified. Thirty years have passed since the specific diseases
      treatment research program was launched, during which the environment surrounding
      intractable diseases has changed significantly. In light of this, "Committee on
      Measures Against Intractable Diseases" was organized in Sept 2001 under the
      Health Science Council. Based on the interim report of the committee, the
      government is going to take new measures against the intractable diseases.

PMID- 15152464
TI  - [Intractable neurological diseases and neurology].
AB  - In intractable neurological diseases, there are often no appropriate treatment
      methods even after admission and the course is frequently chronic. Therefore
      treatment at home is a major choice. In particular, in Parkinson's disease and
      amyotrophic lateral sclerosis, care at home while symptoms are stable is
      appropriate in terms of extension of ADL and the QOL of the patient and family.
      We have performed continuous treatment at home according to our plan for the
      previous 9 years. This treatment was favorably accepted by the patient and family
      without major problems. It is important to organize network to support patient
      with intractable neurological diseases. By virtue of the care insurance system
      established in 2000, services of medical care, health and welfare are being
      collectively provided at present. But, there still remain many issues awaiting
      solution on the support to advanced intractable neurological diseases. A pending
      problem about suction of sputa for the ALS patients serving at home are being
      allowed to non-medical profession like home helper.

PMID- 15152465
TI  - [Change of dementia care management after implementation of long-term care
      insurance].
AB  - Dementia health care management has changed completely since implementation of
      long term care insurance in Japan. Physicians made diagnosis of Alzheimer's
      disease and collaborated with care manager. Then people with dementia can have
      care services like short-stay, day services and also institutional care, if they
      want. Long term care insurance can help or substitute health insurance in old
      age. But still many old people or families want to stay longer in institutions.
      Now government support preventive care including dementia. We studied
      reminiscence therapy on cognitive function for dementia for 2 months. Cognitive
      function was improved after months compared to control group. The results showed
      stimulation by old goods, therapists or collaborators is useful for dementia.
      Reminiscence is one of good activities for dementia at every care services.

PMID- 15152466
TI  - [Critical care neurology--present and future directions].
AB  - In Japan, we have first alerted the necessity of critical care neurology (CCN)
      and neuro-ICU in 2000, however, CCN is still unrecognized. In the United States
      and Germany, CCN has become recognized as one of the important subspecialty in
      neurology, and also, there is progressive increase of neuro-intensive care unit
      (neuro-ICU) after 1990s. In this symposium, the present status, problems, and
      future direction of clinical study and practice in CCN were reviewed from the
      standpoints as follows; 1 Quantitative and sequential analysis of literatures in
      CCN: MEDLINE search disclosed marked increase in CCN-related literatures since
      1990s. 2 Categorical analysis of important literatures selected by German Society
      of CCN. 3 Analysis of clinical practice in CCN through neuro-ICU simulation
      study: in 442 inpatients who admitted to our department during 1998. 4 Analysis
      of requisites in critical care in neurology practice both in diagnostic and
      therapeutic aspects. 5 Historical development of CCN. 6 Evaluation of the effect
      of neuro-ICU. 7 Short-term and long-term problems for the activation of CCN. In
      conclusion, 1) CCN is still immature in Japan, and needs early establishment,
      including neuro-ICU and educational system for developing neurointensivist, 2)
      Extraction of problems, decision-making, and rapid differential diagnosis are
      critical to prevent and manage life-threatening neurological conditions.

PMID- 15152467
TI  - [Acute ischemic stroke].
AB  - Therapeutic nihilism has been overcome by the results of phase III trials of
      intravenous t-PA with 3-hours time window. The integrated team approach can
      increase the number of patients treated rapidly, permit closer monitoring of
      patients, potentially increase the safety of thrombolysis, and streamline
      diagnosis and therapy. The results of randomized clinical trials and meta
      analyses demonstrated that stroke unit treatment made mortality lower,
      hospitalization shorter, good outcome and discharge to the home greater as
      compared to treatment in general medical units. In a nation-wide survey in Japan,
      only 3% of hospitals had a stroke care unit, a specialized unit for acute stroke
      patients. In-hospital mortality was significantly lower in SCU than in ICU or
      general medical wards. In patients with moderate to severe neurological deficits
      at admission (NIHSS score 7 or more), good outcome (mRS score 0 to 2) was also
      more frequently observed in SCU than in other wards. We have to reestablish the
      systems of acute stroke management. It will be achieved by obtaining the approval
      of the use of t-PA, organizing stroke care units in major hospitals, and
      assessing their effects not only on patients' outcome but also on the quality and
      costs of care by their families, medical personnels and our public societies.

PMID- 15152469
TI  - [Critical illness polyneuropathy and myopathy].
AB  - Critical Illness Polyneuropathy (CIP) and Myopathy (CIM), either singly or in
      combination, are a common complication of critical illness. Both disorders may
      lead to severe weakness and require mechanical ventilation. CIP, as initially
      described by Bolton et al., in 1984, is a sensorimotor polyneuropathy that is
      often a complication of sepsis and multiorgan failure. In Japan, Horinouchi et
      al., first reported a case in 1994. CIM has been referred to by a number of
      different terms (acute quadriplegic myopathy, thick filament myopathy, acute
      necrotizing myopathy of intensive care, rapidly evolving myopathy with myosin
      deficiency fibers) in the literature. A variety of serious problems (e.g.,
      pneumonia, severe asthma, and lung or liver transplantation) and the concomitant
      use of high-dose intravenous corticosteroids and nondepolarizing neuromuscular
      blocking agents predispose to CIM. In Japan, Kawada et al., reported a first case
      as acute quadriplegic myopathy in 2000. There is no specific treatment for CIP
      and CIM. Minimizing the use of corticosteroids and nondepolarizing neuromuscular
      blocking agents in a critical illness setting may prove helpful in preventing the
      occurrence of these disorders. The prognosis is directly related to the age of
      the patient and the seriousness of the underlying illness.

PMID- 15152468
TI  - [Current diagnosis and treatment of status epilepticus].
AB  - We reviewed the current diagnosis and treatment of status epilepticus (SE). The
      SE is defined as the condition in which a seizure persists for a sufficient
      length of time or is repeated frequently enough that recovery between attacks
      does not occur. Until recently, the most popular duration of seizures qualifying
      as SE has been 30 min. Nonetheless some clinicians suggest that the duration of
      the seizures that qualifies the SE should be shorter. In clinical settings the
      diagnosis of SE could be difficult without EEGs in patients who have complex
      partial SE or subtle SE, as their manifestation is coma without apparent motor
      sings. Pseudo-SE (psychogenic seizures) should be included in the differential
      diagnosis. Antiepileptic treatment should be administered immediately according
      to the protocol once the diagnosis of SE is made. In patients with refractory SE,
      general anesthesia with propofol or midazolam is recommended. Repetitive
      transcranial magnetic stimulation to the brain is effective for the treatment of
      SE in experimental animals, however further studies are necessary for clinical
      use.

PMID- 15152470
TI  - [Surveillance of prion diseases in Japan: analysis of 409 patients].
AB  - Since April 1999, prion diseases in Japan have been surveyed with the field
      investigation system by the Creutzfeldt-Jakob Disease (CJD) Surveillance
      Committee under the Prion Disease and Slow Viral Infection Research Committee
      sponsored by the Ministry of Health, Labor, and Welfare of Japan. By March 2003,
      a total of 409 patients with prion diseases were reported, including 324 with
      sporadic CJD (79.2%), 49 with inherited prion diseases (12.0%), and 36 with
      infectious prion diseases (8.8%). About 15% of the sporadic CJD cases presented
      with atypical clinical features [long clinical course to akinetic mutism (> 9
      months) or absence of periodic synchronous discharges (PSD) on EEG], including
      thalamic form of CJD (MM2 type) in the autopsy verified cases. The 49 patients
      with inherited prion diseases were classified to 31 with familial CJD, 17 with
      Gerstmann-Straussler-Scheinker (GSS) phenotype, and one with fatal familial
      insomnia; mutations in the prion protein gene included P 102L in 14 (28.6%),
      E200K in 13 (26.5%), V180I in 8 (16.3%), M232R in 3 (6.1%), P105L in 2 (4.1%),
      and so on. All the 36 patients with infectious prion diseases were iatrogenic
      cases due to cadaveric dura mater grafts. Taken together with the data by the
      previous surveillance system, a total of 97 dura mater cases has been reported in
      Japan; the latency period between receipt of a dura mater graft and onset of CJD
      was 122 +/- 53 months (mean +/- SD) including 275 months as the longest one.
      Fortunately, there was no case of variant CJD.

PMID- 15152471
TI  - [Laboratory and imaging studies for the diagnosis of prion disease].
AB  - We evaluated the diagnostic sensitivity of periodic synchronous discharge (PSD)
      in EEG, brain specific proteins in CSF such as neuron specific enolase (NSE), 14
      3-3 protein, and tau protein, and imaging studies performed by T2-weighted MRI
      (T2I) and diffusion-weighted MRI (DWI). 36 patients with a mean age of 68.6 years
      were enrolled. Their diagnostic levels were as follows: seven were definite, 28
      were possible, and one was probable who had a disease-specific point mutation of
      V180I. The diagnostic sensitivities of PSD, NSE, 14-3-3 protein, tau protein,
      DWI, and T2I were 50% (N = 36), 70% (N = 30), 80.8% (N = 26), 87.5% (N = 16),
      92.3% (N = 26), and 42.3% (N = 26), respectively. DWI could revealed the CJD
      related lesions earlier than the appearance of PSD. DWI revealed the lesions even
      in the patients who did not show PSD. For the diagnosis of CJD, DWI and either 14
      3-3 protein or tau protein are useful. Using western blot, we detected the
      protease-resistant PrP in the urine of 11 of 15 CJD patients. We also detected it
      in three of 25 disease control patients. Differing from previous reports, the
      detection of a protease-resistant PrP was not specific to CJD patients. However,
      the sensitivity was 73.3% and the specificity was 88.9%.

PMID- 15152472
TI  - [Prion protein structure and its relationships with pathogenesis].
AB  - In order to explore the structural domains of prion protein (PrP) that are
      required for the isoform conversion, prion formation and neurodegenerative
      effects, we designed a series of PrP deletion mutants and studied, using prion
      infected cultured cells and transgemic (Tg) mice, 1) if these mutants can be
      converted to the abnormal isoform, 2) constitute prions, and 3) cause
      neurodegeneration when converted and accumulated in mouse brains. We discovered
      that a mutant PrP with deletions at the N-terminus and the middle portion
      retained all the three abilities. The molecule named PrP106 was composed of 106
      amino acids, nearly a half of 208 composing wild type PrP. The abnormal isoform
      of PrP106 (PrPSc106) that had been purified from prion-infected Tg mice proved to
      share, with the abnormal isoform of wild type PrP (PrPSc), unique properties such
      as high beta-sheet content and propensity to form fibrous aggregates. These
      findings rationalized the structural analysis of PrPSc106 in comparison with
      PrPSc. The structure of 2D crystals of the two abnormal PrP isoforms was studied
      using electron-microscopy, and the data helped to make the 3D structural model of
      abnormal PrP isoform. Studies with Tg mice expressing other mutant PrPs are
      currently under way.

PMID- 15152474
TI  - [Therapeutics for prion diseases].
AB  - Recent outbreaks of acquired forms of human prion diseases in younger people are
      promoting the development of prophylaxis and therapeutics. One possible target
      for therapeutic interventions is to inhibit the biosynthesis and accumulation of
      an abnormal isoform of prion protein, which is supposed to be a pathogen itself.
      Here, our current in-vitro and in-vivo data on anti-prion chemicals with amyloid
      binding capacity, represented by pentosan polysulfate and thioflavin-related
      chemicals, are presented, and structural aspects on the interaction between prion
      protein molecules and anti-prion chemicals including quinacrine are discussed.
      The current status of clinical trials using quinacrine or pentosan polysulfate is
      also reviewed. Finally, key structure(s) in the prion protein molecules,
      important to inhibit the conversion into abnormal prion protein molecules, are
      discussed in terms of pharmacology, and possibility of the in-silico rational
      drug design is also referred. Exploitation of anti-prion drugs should facilitate
      to solve the enigma of "prion" which can be the only creature against the central
      dogma, in addition to its contributing to the people with the illness or the
      people in high risks.

PMID- 15152473
TI  - [Unfolding chaperone as a prion protein relating molecule].
AB  - Prion protein exists in two different isoforms, a normal cellular isoform (PrPc)
      and an abnormal infectious isoform (PrPSc), the latter is a causative agent of
      prion disease such as mad cow disease and Creutzfeldt-Jakob disease. Amino acid
      sequences of PrPc and PrPSc are identical, but their conformations are rather
      different; PrPc rich in non beta-sheet vs. PrPSc rich in beta-sheet isoform.
      Since the two isoforms have quite different conformation, this host factor might
      be a molecular chaperone, which enables to override an energy barrier between
      PrPc and PrPSc. To examine the protein unfolding activities against collectively
      folded structure exist or not, we constructed an assay system and purified a
      novel molecular chaperone. Unfolding, from S. cerevisiae. Unfolding consists of
      oligomeric ring-like structure with the central cavity and has an ATP-dependent
      protein Unfoldingg activity with broad specificity in vitro, of which targets
      included PrP in beta-sheet form, alpha-synuclein, and A beta protein. We have
      also found that mouse neuroblastoma N2a cells contained the activity. Treatment
      of this factor with an ATP-hydrolyzing enzyme, apyrase, caused the decrease in
      its protein Unfoldingg activity. It was suggested that the purified protein
      probably formed homo-oligomer consisting of 4-5 subunits and its activity was ATP
      dependent.

PMID- 15152475
TI  - [Regeneration of central nervous system: its concept and strategy].
AB  - It had been long believed that our adult mammalian central nervous system (CNS)
      does not regenerate after damage due to injuries or degenerative diseases, as
      Santiago Ramony Cajal had indicated long time ago. Today, however, CNS came to be
      recognized as an important target of so called "regenerative medicine". We have
      been proposing that regeneration of CNS does include the following three
      concepts: i) re-growth of the damaged neuronal axons, ii) replenishment of lost
      neural (or neuronal) cells and iii) recovery of lost neural functions. Here, we
      would like to emphasize that to recapitulate normal neural development is an
      essential strategy for CNS-regeneration. In this review, we would like to take
      Parkinson's disease and spinal cord injury as examples to discuss actual strategy
      aiming for CNS-regeneration.

PMID- 15152476
TI  - [The generation of neural stem cells: induction of neural stem cells from
      embryonic stem (ES) cells].
AB  - Neural stem cells are considered the ultimate lineage precursors to all neurons
      and glia. Despite the significance of neural stem cells in the mammalian brain
      development, their ontogenesis remains unclear. We have established a colony
      forming embryonic stem (ES) sphere assay, where ES cells were cultured in serum
      free media in the presence of leukemia inhibitory factor (LIF) to form floating
      spheres. LIF-dependent ES cell-derived sphere cells showed self-renewal and
      neural multipotentiality, cardinal features of the neural stem cell, but retained
      some non-neural properties and broader potential. We dabbed the cells in the ES
      cell-derived sphere of primitive neural stem cells. LIF-dependent sphere-forming
      cells were also present in the epiblast of embryonic day 5.5-7.5 mouse embryos.
      The generation of the in vivo primitive neural stem cell was independent of Notch
      signaling but the activation of Notch pathway was necessary for the transition
      from the primitive neural stem cell to the neural stem cell. We propose that the
      neural stem cell originates from the pluripotent inner cell mass/epiblast cell
      via the primitive neural stem cell stage under the control of Notch signaling.

PMID- 15152477
TI  - [Differentiation of adult bone marrow cells into neurons and endothelial cells in
      rat brain after stroke in the presence of cytokines].
AB  - Multipotent adult progenitor cells, which can differentiate into mesenchymal
      cells as well as cells with visceral mesoderm, neuroectoderm and endoderm
      characteristics, have been identified in the bone marrow. We examined whether
      bone marrow-derived cells can differentiate into the major cell types in the
      brain, including neuron, astrocyte, microglia and endothelium, in response to
      cerebral focal ischemia under treatment with cytokines. Bone marrow cells, which
      were sampled from green fluorescent protein (GFP)-expressing transgenic mice,
      were transplanted into irradiated female C57 Black/6 mice. Two months later, the
      recipient mice received permanent occlusion of the middle cerebral artery, then
      were treated with cytokines. One month after the occlusion, GFP-expressing cells,
      considered to be bone marrow-derived, were identified as neurons, endothelial
      cells, microglias and macrophages by means of NeuN, CD31, major
      histocompatibility complex class I antigen, and CD45 labeling, respectively,
      observed with confocal microscopy. These results indicate that the bone marrow
      derived cells are, at least in part, a source of neurons as well as endothelial
      cells generated in response to cerebral infarction, in the presence of cytokines.
      This finding may suggest a new therapeutic strategy to enhance neuronal and
      vascular regeneration after stroke in the clinical field.

PMID- 15152478
TI  - [Brain ischemia--regenerative therapy using human neural stem cells].
AB  - The mortality of stroke is still the those of single organs. Even if patients
      survive the brain attack they often suffer from not only motor functional
      disability but also psychiatric problems such as post-stroke depression and
      decrease in spontaneity. The stoke is the number one cause of the bed-ridden
      state "Netakiri". Presently only anti-thrombotic and anti-oxidative stress
      therapies are available and the ischemic core destroyed immediately after the
      stroke could never be rescued. We have started to study the basic aspect of
      transplantation therapy of cerebral infarction using neural stem cells. Using a
      focal ischemic model of the gerbil by repeated occlusion of the unilateral
      carotid artery, we grafted human neural stem cells which were cultured and
      proliferated for a long period. Grafted animals showed significant and marked
      improvement in all three functions including motor, sensory and cognitive
      functions associated with a significant reduction of infarction volume. Synaptic
      contacts between neurons from grafted human neural stem cells and host neurons
      were confirmed by immuno-electron microscopy. This is a very encouraging report
      although it is necessary to elucidate the precise mechanism of the functional
      recovery or the effect of neural stem cell transplantation.

PMID- 15152479
TI  - [AAV vector-mediated gene transfer and its application to the nervous system].
AB  - AAV vectors are considered to be promising gene-delivery vehicles for gene
      therapy, because they are derived from non-pathogenic virus, efficiently
      transduce non-dividing cells, and cause long-term gene expression. Appropriate
      AAV serotypes are utilized depending on the type of target cells; e.g., neurons
      are efficiently transduced with AAV2 and AAV5 vectors, and an AAV1 vector is most
      suitable for muscles. Among various neurological disorders, Parkinson's disease
      (PD) is one of the most appropriate candidates of gene therapy. PD is a
      progressive neurodegenerative disorder that predominantly affects dopaminergic
      neurons in the substantia nigra. There are two major approaches to gene therapy
      of PD; i.e., 1) intrastriatal expression of dopamine (DA)-synthesizing enzyme
      genes, and 2) neuroprotection using the glial cell line-derived neurotrophic
      factor (GDNF) gene to prevent the disease progression. As for the initial step of
      clinical application, AADC (aromatic L-amino acid decarboxylase; the enzyme
      converting L-DOPA to DA) gene transfer in combination with oral administration of
      L-DOPA would be appropriate, since DA production can be regulated by the dose of
      L-DOPA. Preclinical studies are being conducted in MPTP-parkinsonian monkeys. AAV
      vector-mediated gene therapy would be feasible as a novel treatment of PD in the
      near future.

PMID- 15152480
TI  - [Clinical practice guidelines in Japan: toward their appropriate use and
      diffusion].
AB  - In Japan, the governmental report on health technology assessment in 1999
      referred to the need to develop evidence-based clinical practice guidelines. The
      Ministry of Health and Welfare established priorities for the development of
      clinical practice guidelines, and started several projects. About 20 clinical
      practice guidelines are to be developed by 2004. However, what "guideline" means
      and how "guidelines" work are unclear because the word "guideline" is ambiguous
      in Japan. Although it is generally accepted that "directives are stronger than
      recommendations, which are stronger than guidelines" in the western countries,
      Japanese people do not usually recognize these distinctions and tend to regard
      guidelines as mandatory directives even in individual cases. Patients, consumers
      and legal professionals may overestimate the authority of clinical practice
      guidelines when they see them. What clinical practice guidelines are, or are not
      should be clarified appropriately. Autumn 2003, the Japan Council for Quality
      Health Care will open the information service that provides practice guidelines
      and related literature. This will be accessible to both healthcare professionals
      and the general public. Much remains to be done to bring other stakeholders to
      the table. All of Japanese society can, and needs to, participate in the process
      of developing a consensus on clinical practice guidelines.

PMID- 15152481
TI  - [Problems in development and use of guidelines for clinical practice].
AB  - According to the Agency for Healthcare Research and Quality in the USA, the
      characteristics to be fulfilled by clinical guidelines are validity,
      reproducibility, reliability, clinical flexibility, clarity and scheduled review.
      However, most clinical guidelines do not necessarily fully satisfy these factors.
      I have been engaged in the development of evidence-based guidelines for the
      management of stroke in Japan. Problems in development of guidelines are as
      follows. The first is the lack of high level evidence such as randomized
      controlled trials, which influences recommendation grade. In the case of clinical
      guidelines for treatment of cerebral hemorrhage in the acute stage, the
      recommendation grade (C1, C2), which means a lack of sufficient scientific
      evidence, covered 86% of all recommendation items. The second is ease of clinical
      application. Evidence based clinical guidelines are not likely to be easy to use
      if sufficient high-level scientific evidence is not available. It must be
      realized that guidelines can only be applied to 60 to 95% of patients. Depending
      on the patient, setting, and other factors, guidelines can and should be tailored
      to fit individual needs. Deviations from guidelines will be fairly common and can
      be justified by differences in individual circumstances.

PMID- 15152482
TI  - [Issues of practice guideline].
AB  - "Practice Guideline (PG) or management guideline" is not an impeccable guideline
      but a tool to support a clinical decision, i.e., one of factors to make a
      clinical decision. When making a clinical decision, medical practice is
      finalized, taking into consideration of PG, patient's preference, social and
      national healthcare system. Even if PG provides a treatment method on the basis
      of high level evidences, we should not always uniformly apply to every patient.
      We can practice better with combination of PG, physician's expertise, patients'
      preference. When consulting PG, it is recommended to confirm in advance what
      society/organization prepared PG, purpose of preparation, preparation process,
      and developmental method, including social fairness whether healthcare cost is
      assumed in PG or whether industry is a substantial editor. As to the questions
      whose answer is not mentioned in PG, their controversial points have to be
      defined and assessed, retrieving literatures. This is so called implementation of
      "Evidence-Based Medicine (EBM)." The practice of EMB provides better evidences.
      PG is fated to be always outdated when published because new evidence will be
      additionally published, and therefore, it is always required to search for new
      evidences available at daily practice.

PMID- 15152483
TI  - [The significant of practical guideline in social context].
AB  - After drawing clinical practice guideline, we are going to face the significant
      of practice guideline in social context, both negative aspect and positive
      aspect. Negative aspect is the worry about misuse concerning medical malpractice
      lawsuits in courtroom. By analyzing the resent 3 Supreme Court decisions, I
      explain that practice guideline is the only one of recourses to determine medical
      negligence. Positive aspect is that practical guidelines would be the one of
      tools, which improves informed consent between medical practitioners and patients
      under the some conditions. Proper using practice guideline could reduce the
      conflict on informed consent.

PMID- 15152484
TI  - [Recent changes in the neurology residency program in the United States].
AB  - Residency in the United States has been known as one of the most organized
      systems for postgraduate medical education in the world. However, recent changes
      in the social, ethical and economic environment in the healthcare have brought
      new demands to the residency education. This review focuses on the new changes
      introduced by the Accreditation Council for Graduate Medical Education and
      Residency Review Committees, especially the changes directly relevant to
      neurology. These include changes in evaluation of residents and programs, work
      hours of residents and training curriculum. Additionally, residency program
      directors are facing new challenges of protecting healthcare private information,
      managed care, underrepresented minorities and visa acquisition by international
      medical graduates. Consequently, the workload of residency program directors has
      become more demanding.

PMID- 15152485
TI  - [How should we establish professional education system for neurologists?].
AB  - A professional education system for neurologists has been provided at Department
      of Neurology, Niigata University, which includes neurophysiology, neuroradiology,
      and neuropathology (optional). A 6 month-course of "chief resident" has also been
      implemented in the program. Although these systems have functioned well,
      hospitals providing such education programs are limited. To encourage the
      education programs, various issues need to be discussed. 1. The number of staffs
      is limited in most of the hospitals, limiting the capacity for providing such
      programs. 2. We need to recruit at least a given number of neurologists to make
      such systems work properly. 3. We need to discuss on the relationship between
      professional education system for neurologists and programs in the graduate
      school. To establish standardized professional education system for neurologists
      in Japan, Japanese Society of Neurology is strongly encouraged to play major
      roles.

PMID- 15152486
TI  - [Debate: is the neurology residency program of Japan to be standardized?: "Yes"].
AB  - Japanese Neurological Association (JNA) should establish the standardized
      nationwide neurology residency program, and JNA should disclose the minimal
      requirements of both knowledge and practice for the board of neurology to the
      public and guarantee the quality of the neurology specialists. Standardization of
      the residency program will facilitate not only standardization of the knowledge,
      skill and art of the neurology specialists but also inter-institutional
      cooperation among the individual teaching hospitals in completing the training
      programs for the residents. Neurology professionals whose quality is guaranteed
      by JNA will satisfy the demands of the patients who want excellent neurological
      services of high quality and safety, and will be favorably accepted by high level
      hospitals which supply medical services of high quality. Nationwide standardized
      neurology residency program will thus be welcomed by both residents who aim for
      the board of neurology and teaching hospitals which accept the residents. It will
      facilitate to efficiently educate neurology residents for specialists, and will
      benefit the patients and hospitals. JNA should establish the standardized
      neurology residency program as soon as possible and go to action to socially and
      economically improve the condition and treatment of the specialists (for example;
      approval of doctor's fee by the government).

PMID- 15152487
TI  - [Debate: the postgraduate neurology education should be standardized? No].
AB  - According to the previous survey of postgraduate neurology education in Japan,
      there is a wide range of variability among training hospitals in terms of the
      number of neurologists available for the postgraduate education, the number of
      beds available for neurological teaching, facilities, the number of residents,
      diseases of main interests, and subspecialty fields within neurology. Practically
      speaking, therefore, it is not suitable and it is even impossible to completely
      standardize the way of postgraduate education throughout the country. 'Essential
      core curriculum' which consists of history taking and neurological examination,
      and education of basic neuroscience knowledge related to clinical neurology,
      combined with clinical neurophysiology including electroencephalography (EEG) and
      electromyography (EMG), clinical neuropathology including muscle and nerve
      biopsy, and neuroradiology, could be standardized to a certain degree at least in
      part. Other related fields such as neuropsychology, rehabilitation, neuro
      ophthalmology, pediatric neurology, neurosurgery, psychiatry and neurogenetics
      can be educated in certain designated centers of each specific field depending on
      the resident's choice. Although 'essential core curriculum' could be standardized
      to a certain degree, 'flexibility program' is more practical in Japan at least in
      the years to come.

PMID- 15152488
TI  - [SMON--a model of the iatrogenic disease].
AB  - The subacute myelo-optico-neuropathy (SMON) was hazard caused by clioquinol, an
      antiseptic, prescribed for the treatment of diarrhea and other bowel symptoms.
      Its overdosing and long-term taking led to the occurrence of SMON, for which
      physicians should be responsible. Clioquinol, originally a disinfectant powder
      for external use, was diverted later to a drug for internal use to sterilize the
      bowel where no intestinal absorption or action after absorption was expected. An
      annotation on the 6th Revision of the Japan Pharmacopoeia (1954) allowed
      irregular increase in its dosage depending on the severity of illness. An
      annotation on the 7th Revision (1961) ignoring the 6 papers published in the
      1930's, 1940's or 1950's claimed that its metabolism was poorly known, yet
      neglected significant side effect and substantial absorption from the intestine.
      Its characterization as a superficial disinfectant helped the annotators be less
      interested in its absorption and its internal actions and side effects. Attention
      paid by clinicians to a polyneuropathy-like syndrome that complicated an
      uncontrollable hemorrhagic diarrhea (1958) and an encephalomyelitis or a
      paralysis of the lower half of the body associated with diarrhea or other bowel
      symptoms (1960, 1961) started the recognition of a new disease. During the
      dispute induced by the mass occurrence of the disease in several instances
      postmortem examination with neuropathologic expertise, especially of T. Tsubaki,
      Y. Toyokura and H. Tsukagoshi (1964), characterized SMON as a non-inflammatory
      new disease of the spinal cord, optic nerve and peripheral nerve with a pseudo
      systemic degeneration of posterior and lateral columns and, therefore played a
      decisive role in establishing the truth of SMON. The discovery of the green hairy
      tongue (the tongue coated with green hairs) of SMON by T. Takasu, A. Igata and Y.
      Toyokura (January 1970) aroused researchers' interest in the green color of SMON
      and thereby began solving the cause of SMON. The discovery of the green urine in
      SMON patients by A. Igata, M. Hasebe and T. Tsuji (May 1970) especially
      facilitated the identification of the green substance in SMON that was achieved
      by M. Yoshioka and Z. Tamura (June 1970). The green color was derived from a
      chelate compound of clioquinol with ferric iron. The early epidemiological
      analysis related clioquinol taking to the occurrence of SMON well enough for the
      Japanese Government to take an administrative measure for the temporary
      suspension of selling clioquinol containing drugs and the postponing of their use
      (September 1970). Extensive and intensive multidisciplinary investigations
      conducted for the subsequent 20 months led to the conclusion by the SMON
      Investigation and Research Committee (Head: R. Kono) that the neurological
      disorders of patients who were diagnosed as SMON for the most part were caused by
      taking clioquinol (March 1972). Close clinical observation of patients opened a
      way to recognize a new disease and elucidate its cause. Expert specialized
      technical knowledge and skills established the firm knowledge of the new disease.
      The study of SMON began as a personal research and after its achievement was
      exposed to the public a great many investigators in different fields concerted
      efforts to solve problems. Both steps were indispensable for completing the
      study.

PMID- 15152489
TI  - [Infectious prion disease: CJD with dura mater transplantation].
AB  - Prion diseases include scrapie, BSE and CWD in animals, and spontaneous, familiar
      and infectious Creutzfeldt-Jakob disease(CJD) in human. Infectious prion diseases
      include kuru, variant CJD and iatrogenic CJD. CJD has been transmitted from human
      to human by contaminated cadaveric dura mater grafts and by cadaveric pituitary
      hormones. To date, CJD associated with dura mater grafts, reaching 156 cases, has
      been reported in 17 countries. More 2/3 of cases have been reported in Japan.
      Nationwide survey and recent information documented 105 dura-related cases during
      the period between 1979 and 2003. At least 91 cases received same brand of dura
      mater by a single German company. Age at disease onset in cases with dura-related
      CJD was younger (54.2 +/- 14.2 years) than sporadic CJD (64 +/- 10 years). Two
      groups of dura-related CJD are manifest in clinical course and pathological
      characteristics, such as rapidly progressive group and slowly progressive.
      Rapidly group was similar to cases with classical CJD in clinical features and
      shot duration to death from onset. Slowly progressive group developed akinetic
      mutism longer than 1 year, and characterized by florid plaques in the brain
      (Kitamoto).

PMID- 15152490
TI  - [Reye syndrome and drug induced encephalopathy].
AB  - Reye syndrome, characterized by acute encephalopathy, selective liver damages, a
      fatty degeneration in visceral organs and miserable prognosis, is probably caused
      by various drugs, especially antipyretic such as acetylsalicylate. The incidence
      of the disease has been decreased by prohibition of administration of aspirin for
      children with high fever, especially caused by influenza infection in western
      countries, also in Japan. The pathophysiology of the disease has extensively
      studied, however, still being unknown to be dissolved. Our previous study of
      lipid analysis of brain from experimental measles encephalitis revealed an
      increase of cholesterol ester and decrease of sphingomyelin. As cholesterol ester
      is synthesized from cholesterol and fatty acids catalyzed by acylCoA
      acyltransferase(ACAT), ACAT activity can be increased in the experimental animal
      brain. In the present report, ACAT m-RNA could not be expressed in control brain
      but in the experimental animal brain, so ACAT may play a role in pathogenesis of
      Reye syndrome.

PMID- 15152491
TI  - [Neurological complication due to the drug and the maneuver for the treatment and
      prevention of cerebrovascular diseases: iatrogenic neurology].
AB  - Neurological sequela which occur with the medication and procedure to treat or
      prevent cerebrovascular diseases are reviewed. The report by the NINDS upon the
      recombinant tissue plasminogen activator (rt-PA) for cerebral infarction showed
      overall improved prognosis and increased number of cerebral hemorrhage from 1 to
      9. Individual approach rather than statistical analysis should be applied to the
      adverse effect of the treatment. The rhabdomyolysis by statin, the HMG-CoA
      reductase inhibitor, is well known. The frequency of elevation in serum creatine
      kinase activity increases from water-soluble statin to lipid-soluble statin and
      to statin of longer half-life and with entero-hepatic recirculation. All of the
      interventional procedure such as embolization, stent, intravascular thrombolysis,
      endarterectomy and EC-IC bypass are possibly complicated by bleeding, arterial
      occlusion, distal embolism and so on. Guidelines are also a possible source of
      iatrogenic diseases. For example, 2003 European Society of Hypertension-European
      Society of Cardiology guidelines for the management of arterial hypertension
      recommend at least 3 months of non-pharmacological treatment before starting the
      anti-hypertensive medications. The possibility to develop stroke within 3 months
      after the initial examination, however, is not zero. This is what can be called
      as guideline-induced neurological disease, of which practical physician should be
      reminded.

PMID- 15152492
TI  - [Neurological effects of chemical and biological weapons].
AB  - Neurological manifestations of chemical and biological weapons are reviewed.
      Nerve agents in current use, storage, or production include tabun, sarin, soman
      and VX. The initial effects of exposure to a nerve agent depend on the dose and
      on the route of exposure. Sarin, the agent studied most thoroughly in man in
      Matumoto and Tokyo attacked by Aum shinrikyo will cause miosis, rhinorrehea and
      shortness of breath are initial complaints immediately after inhalation exposure
      of the vapor. The severe cases showed loss of consciousness and convulsions.
      Respiratory arrest may occur. The most toxic of the nerve agents is VX. It is
      thought to be 100 times as toxic as sarin for humans by the percutaneous rout.
      The similar findings to sarin exposure are also observed in cases exposured to
      VX. Atropin and PAM will be effective in the early stage. BZ (benzilate) is a
      delayed onset incapacitation agent. It causes severe hallucination. The cyanide
      compounds are among the most rapidly acting of war gases, resulting in death.
      Anthrax has been the most attractive biological weapon for a long time. Anthrax
      is an acute bacterial infection of the skin and lungs in man and animals.
      Meningoencephalitis has been reported in the terminal stage in anthrax infection.
      In autopsy, it is really confirmed in the characteristic findings of the
      meningeal abnormality. The potential weaponization of variola virus continues to
      pose a military threat because the aerosol infectivity of the virus and the
      development of susceptible populations. A high rate of lethality, a staunch
      resistance to treatments and a rapid onset of severe generalised muscle weakness
      make botulinum toxin a suitable agent for biological warfare particularly by oral
      administration.

PMID- 15152493
TI  - [EBM of cerebral infarction: message from mega-studies].
AB  - A meta-analysis by the Antithrombotic Trialists' Collaboration showed significant
      reduction of vascular events including stroke. MI, and vascular death by
      antiplatelet therapy in high risk patients with obstructive vascular disease. Low
      dose aspirin of 75 to 150 mg was most effective and its very low dose below 75 mg
      was not proven effective. Cilostazol significantly reduced the risk of recurrence
      in Japanese patients with ischemic stroke, mostly lacunar stroke. Large
      randomized controlled trials (RCTs) such as MATCH, ACTIVE, and CHARISMA are
      ongoing to see an effect of aspirin plus clopidogrel. Among patients with non
      valvular atrial fibrillation (NVAF), warfarin is recommended in patients at age
      over 75 years, and those with history of stroke or TIA, hypertension, congestive
      heart failure, diabetes or coronary heart disease, while aspirin can be
      alternative in patients without any of these risk factors of stroke. Target INR
      of 2.0 to 3.0 is recommended in these NVAF patients, although lower INR of 1.6 to
      2.5 is recommended to avoid hemorrhagic stroke in elderly patients with NVAF.
      SPORTIF was conducted to compare ximelagatran, an oral thrombin inhibitor, with
      warfarin in NVAF patients with risk factors, and the result showed a comparable
      efficacy and safety of ximelagatran. WARSS did not show any efficacy of warfarin
      over aspirin in any subtypes of ischemic stroke patients without NVAF, acute MI,
      left ventricular thrombi, or prosthetic heart valve. PICSS, a substudy of WARSS,
      also did not show any efficacy of warfarin over aspirin in stroke patients with
      patent foramen ovale (PFO), although warfarin might be recommended in PFO
      patients with deep vein thrombosis.

PMID- 15152494
TI  - [Advances in the diagnosis and treatment of cerebral ischemia during the acute
      phase].
AB  - Recent advances in MRI technology and the development of effective
      neuroprotective agents has improved the outcome of stroke. In order to salvage
      tissue after an ischemic insult it is important to differentiate the core and
      penumbra area of the ischemic lesion. The penumbra surrounds the ischemic core,
      damage in this area is reversible if effective neuroprotective agents are given
      and reperfusion occurs. In this symposium detection of penumbra in an ischemic
      lesion using diffusion weighted imaging (DWI) and perfusion imaging (PI),
      diffusion-perfusion mismatch, and indications for thrombolytic therapy are
      discussed. If a hypoperfusion area is revealed with PI without a corresponding
      lesion indicated with DWI or when the DWI lesion is less than one third of the PI
      lesion, combined thrombolytic and neuroprotective therapies are recommended. In
      contrast, when both PI and DWI show an identical lesion, only neuroprotective
      therapy is advised. Additionally, newly developed neuroprotective agents,
      especially the combined effect of rt-PA and the immunosuppressant, FK506, on an
      embolic infarct model are discussed.

PMID- 15152495
TI  - [Molecular mechanism of brain infarction].
AB  - Through many experimental brain ischemia studies, it has been suggested that all
      of the cellular elements in the central nervous system show dynamic stress
      responses depending on the degree of environmental changes induced by ischemia
      and reperfusion. In this symposium, first we reviewed the pathogenic role of
      microvascular stasis (i.e., secondary ischemia) caused by the primary ischemic
      event and demonstrated the important role of cell adhesion molecules through the
      experiments using ICAM-1 knock-out mouse as a model of brain
      ischemia/reperfusion. Next, we discussed the ischemia-induced neuronal cell
      responses in relation to the apoptosis-like selective neuronal death and the
      induction of adopted stress responses including stress protein synthesis and
      'ischemic tolerance' phenomenon. A variety of stress proteins induced by ischemic
      stress have been reviewed in relation to their pathophysiological roles in the
      ischemic brain. Finally, we reviewed the important pathogenic roles of
      endoplasmic reticulum (ER) stress as well as adaptive responses of ubiquitin
      proteasome system in ischemia-induced neuronal cell death. For the development of
      a novel therapeutic agent against ischemic stroke, it is quite important to
      clarify both the negative and positive cellular responses induced by brain
      ischemia/reperfusion.

PMID- 15152496
TI  - [Gene therapy and neuroprotection for cerebral infarction].
AB  - Topical application of GDNF protein greatly reduced the infarct size and brain
      edema at 24 hr of continuous MCAO in rats. The reduction of the infarct size was
      not related to a change of cerebral blood flow (CBF), but was accompanied by
      marked reduction of positive cells for TUNEL and caspases in the affected area.
      GDNF protein showed a direct protective effect against ischemic brain damage, but
      not secondary by improving CBF. Pretreatment of animals with Ad-GDNF 24 hr before
      the subsequent 90 min of transient MCAO effectively reduced infract volume and
      area without affecting regional CBF compared to the vehicle or Ad-LacZ animal
      groups. Free radical scavenger edaravone effectively reduced brain edema, infarct
      size, and peroxidative markers of protein, lipid and DNA. Thus, gene therapy and
      neuroprotective strategy have a great potential for reducing ischemic brain
      damage of human stroke patients in the near future.

PMID- 15152497
TI  - [A stem cell therapy for stroke].
AB  - It has been reported that the adult mammalian harbors stem cells or progenitors
      that retain the potential for both neural production and differentiation.
      Recently, several progenitors derived from non-neural samples as well as the
      neural tissues in humans are thought to be a good candidate for the regenerative
      medicine. Multipotent embryonic stem cells prepared from the fertilized egg or
      neural stem cells from fetus may be used as allotransplants. Progenitors derived
      from adult brain, bone marrow, code blood, or lipid can be used as
      autotransplants. Bone marrow in adult mammals contains several types of precursor
      and stem cells such as hematopoietic stem cells, non-hematopoietic stem cells,
      and other unknown precursor cells. The distinct population of progenitor cells in
      the bone marrow are thought to retain the potential for both neural production
      and differentiation, and may contribute to a therapeutic strategy for stroke. In
      the present report, the possible therapeutic strategy of the stem cell
      transplantation for the stroke is discussed.

PMID- 15152498
TI  - [Mechanisms of neurodegeneration in polyglutamine diseases].
AB  - Neurodegenerative diseases are characterized by (1) age of onset usually in late
      adulthood, (2) insidious onset and gradual progression, (3) neuronal loss in
      particular regions of the nervous system with the distribution being unique to
      each neurodegenerative disease, and (4) familial occurrence is occasionally
      encountered in theses diseases, but the majority is "sporadic". Recent progresses
      in molecular genetic studies have enabled to identify the causative genes. Among
      the hereditary neurodegenerative diseases, polyglutamine diseases are of
      particular interest, because common pathophysiologic mechanisms are considered to
      underlie the neurodegenerative processes. In transgenic mice carrying a full
      length mutant DRPLA gene, obvious neuronal loss was not observed despite the
      severe neurological phenotypes. We have found intranuclear accumulation of mutant
      proteins with expanded polyglutamine stretches leads to "reversible"
      transcriptional dysregulation through interaction of expanded polyglutamine
      stretches with TAF130, a transcriptional coactivator. The fact that there is no
      obvious neuronal loss in the transgenic mice indicate that the processes of
      neurodegeneration are "reversible" neuronal dysfunctions, and, furthermore,
      strongly encourages development of therapeutic approaches for neurodegenerative
      diseases.

PMID- 15152499
TI  - [Polyglutamine diseases: a pathologic view].
AB  - It has been widely accepted that there is a discrepancy between clinical features
      and lesion distribution evaluated by neuronal loss in the polyglutamine diseases
      including Huntington's disease and dentatorubral-pallidoluysian atrophy (DRPLA).
      Neuronal intranuclear inclusion (NII) is a characteristic feature of the
      polyglutamine diseases; however, its significance in the pathogenesis is still a
      matter of controversy. In a study of DRPLA brains, we found that intranuclear
      diffuse accumulation of mutant proteins with expanded polyglutamine stretches is
      another pathology involving many neurons in various nervous system regions
      including the dentatorubral and pallidoluysian systems, in which the number of
      affected neurons was constantly high. Of note was that affected neurons in some
      regions such as the cerebral cortex extremely vary in number depending on the
      size of CAG repeat, suggesting that these situations may be responsible for a
      variety of phenotypes including dementia in DRPLA. The nuclear pathology was also
      detectable in a wide range of CNS regions in Machado-Joseph disease and
      Huntington's disease. The nuclear pathology may be a characteristic feature and
      exert certain influence on certain nuclear functions of many neurons in the
      polyglutamine diseases.

PMID- 15152500
TI  - [Mechanisms to control degradation of polyglutamine-containing protein].
AB  - Machado-Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is
      neurodegenerative disease which is caused by polyglutamine expansion in a
      responsible gene product, MJD1/Ataxin3. MJD1 has now been shown to undergo
      ubiquitylation and degradation by proteasome-dependent pathway. MJD1 with
      expanded polyglutamine tract was more resistant to degradation than normal MJD1.
      We established an in vitro system of ubiquitylation of MJD1, thereby
      biochemically purified activity to mediate polyubiquitylation of MJD1 from rabbit
      reticulocyte lysate. An AAA-family ATPase VCP was isolated from the active
      fraction, and found to binds to MJD1. Furthermore, UFD2a, a mammalian ubiquitin
      chain assembly factor (E4), associated with VCP and induced polyubiquitylation of
      MJD1. UFD2a markedly promoted ubiquitylation and degradation of MJD1 with
      expanded polyglutamine tract, resulting in the clearance of MJD1 protein. In
      contrast, dominant-negative mutant UFD2a reduced the degradation rate of MJD1,
      leading to the formation of intracellular aggregation. In Drosophila model,
      overexpression of UFD2a significantly suppressed the neurodegeneration induced by
      expression of MJD1 with expanded polyglutamine tract. These findings suggest that
      E4 is a rate-limiting factor of degradation of pathologic polyglutamine
      containing proteins, and may give a potential tool for gene therapy to control
      the clinical conditions of MJD.

PMID- 15152501
TI  - [Development of therapeutics for spinal and bulbar muscular atrophy (SBMA)].
AB  - Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a
      hereditary motor neuron disease that affects males, caused by the expansion of a
      polyglutamine (polyQ) tract in androgen receptor (AR). Female carriers are
      usually asymptomatic. The transgenic mouse (Tg) model carrying a full-length
      human AR with expanded polyQ has significant gender-related motor impairment.
      This phenotype is inhibited by castration, which prevents nuclear translocation
      of mutant AR. Leuprorelin, an LHRH agonist that reduces testosterone release from
      the testis, also rescues motor dysfunction and nuclear accumulation of mutant AR
      in the male Tg. Over-expression of a molecular chaperone HSP70, which renatures
      misfolded mutant AR, ameliorates neuromuscular phenotypes of the Tg by reducing
      nuclear-localized mutant AR. HSP70 appears to enhance the degradation of mutant
      AR via ubiquitin-proteasome pathway. These experimental approaches indicate the
      possibility of clinical application of drugs, such as leuprorelin, for SBMA
      patients.

PMID- 15152502
TI  - Risk management practice--living with it in QHealth.

PMID- 15152503
TI  - Yes, we believe there is a nursing shortage....

PMID- 15152505
TI  - Medicare. The battlelines are drawn.

PMID- 15152504
TI  - Queensland's new Minister for Health, Mr Gordon Nuttall spoke to John Moran for
      The Queensland Nurse. Interview by John Moran.

PMID- 15152506
TI  - Power to change.

PMID- 15152507
TI  - [Posterior laparostomy for retroperitoneal infections caused by periampullar
      endoscopic procedures: an old technique for an emerging disease].
AB  - Duodenal perforations occur in 0.4-1% of endoscopic manoeuvres. In cases of
      periampullary injury, the best therapeutic approach is still controversial.
      Generally, the first treatment will be conservative, but in some patients large
      retroperitoneal infections requiring surgical treatment develop. Six patients,
      referred to our unit for extensive retroperitoneal collections and unstable
      septic conditions as a consequence of periampullary duodenal perforation during
      ERCP, were treated by right posterior laparostomy with twelfth rib resection. The
      septic process was treated efficaciously by the open posterior approach that
      favoured the spontaneous closure of the duodenal leak after a mean period of 14.5
      +/- 5.2 days. No hospital deaths or major complications were recorded. Late
      incisional hernia developed in one case. The technique of posterior laparostomy
      with twelfth rib resection permits adequate debridement and drainage of both the
      upper and lower parts of the retroperitoneal space involved in infection after
      periampullary duodenal perforations. The good control of both the retroperitoneal
      septic process and the duodenal secretions facilitates the spontaneous closure of
      the duodenal leak, thus avoiding the risk of more complex and dangerous
      procedures.

PMID- 15152508
TI  - [Post-thyroidectomy hypocalcemia: clinical and laboratory findings].
AB  - Hypocalcaemia is a possible sequela of thyroidectomy, the causes of which are not
      fully understood. Today, correct surgical technique is the most important factor
      in decreasing the incidence of hypocalcaemia. We analysed 1223 patients (930
      total thyroidectomies, 293 hemi-thyroidectomies) treated in our institute from
      January 1995 to July 2003. Serum calcium, ionized calcium, parathyroid hormone
      and phosphoraemia were screened pre- and postoperatively. Hypocalcaemia, as
      defined by a serum calcium concentration below 8.5 mg/dL, occurred in 241
      patients (25.1%). In 90.9% of these patients, serum calcium was normal 7 days
      after thyroidectomy. In three patients we registered permanent hypoparathyroidism
      180 days after thyroidectomy. We found a statistically significant difference in
      the incidence of hypocalcaemia between patients treated for benign disease and
      those treated for malignant disease with a greater incidence in the latter group
      (P < 0.05). Several factors are important in determining the incidence of post
      thyroidectomy hypocalcaemia but the inadvertent excision of the parathyroid
      gland, ischaemia and injury are the main causes of the lowering of serum calcium
      concentrations.

PMID- 15152510
TI  - [Thyroidectomy for thyroid carcinoma. Our experience].
AB  - The surgical management of thyroid carcinoma involves different degrees of
      lymphadenctomy, according to features such as the nature, the site and the
      severity of the disease. The authors present their experience in order to
      contribute to the debate on the standard management of nodal metastasis in well
      differentiated thyroid cancers. The authors describe their six years of
      experience in 302 thyroid cancer patients with a total of 291 thyroidectomies
      performed. According to the different pathological findings, the treatment
      involved a monolateral dissection in 42 patients and a bilateral modified neck
      dissection in 21. A number of anatomical considerations regarding the pathway of
      lymphatic drains are summarized and follow-up results are also presented. The
      slow progression of the disease and its low incidence make long-term prospective
      studies difficult, thus hindering any definitive assessment of lymph node
      management in well-differentiated thyroid cancers.

PMID- 15152509
TI  - [Basedow's disease associated with benign and malignant nodular disease of the
      thyroid: diagnosis and treatment].
AB  - Nowadays the prevalence of thyroid nodules in Graves' disease (GD) is estimated
      as ranging from 15 to 33% and several studies support a high risk of thyroid
      cancer in this condition. The present study presents a retrospective analysis of
      41 cases of GD submitted to total thyroidectomy from 1995 to 2003, aimed at
      discovering the most useful elements for an optimal diagnostic and therapeutic
      strategy. We identified 23 patients with coexisting nodular goitre (nodular
      variants of GD) and among these we carried out a comparative study of 12 cases
      with only benign nodules and 7 with thyroid carcinoma detected prior to the
      operation. Four cases were not considered because of incidental microcarcinomas.
      We found no significant differences in the number, average size and radionuclide
      imaging of nodules in the two groups. In contrast, analysis of ultrasonographic
      findings showed that hypoechogenicity correlated closely with malignancy,
      particularly if associated with ill-defined margins, microcalcifications and
      intranodular vascular patterns, whereas hyperechogenicity was a typical
      appearance of benign lesions. Our study suggests that routine thyroid US scans
      should be considered for complete evaluation of GD, since this pathology
      frequently implies the development of thyroid nodules which are not always
      detectable at clinical or radionuclide examination. Surgery is mandatory when
      nodules with suspicious ultrasonographic features are found and if malignancy
      cannot be excluded at fine needle aspiration cytology.

PMID- 15152511
TI  - [Prognostic significance of lymphatic micrometastasis of esophageal
      adenocarcinoma].
AB  - The aim of the study was to test the hypothesis that a subgroup of patients
      considered N0 at standard single-section pathological examination may have occult
      lymph-node metastases (micrometastases) associated with a poor prognosis. Fifty
      nine patients with oesophageal adenocarcinoma undergoing resection were studied
      by standard histological examinations, serial sections and immunohistochemistry,
      and their long-term prognoses were compared. Eight (26%) out of 31 patients
      previously staged as pN0 at standard histological examination were staged as pN1
      or Pn2 by serial sections and/or immunohistochemistry and had a prognosis which
      was significantly worse than that of true pN0 patients (5-year survival: 38% vs
      76%, respectively; P < 0.05) and similar to that of pN1 patients. More than a
      quarter of those patients classified as pN0 at standard histological examination
      may have occult lymph node metastases at serial sections and/or
      immunohistochemistry and have a prognosis similar to that of pN1 patients.

PMID- 15152512
TI  - [Surgical treatment of primary acquired inguinal hernia with the use of
      polypropylene prosthesis].
AB  - In the "Villa dei Fiori" Nursing Home of Mugnano di Napol, from 1 November 1997
      to 31 October 2000, 384 patients were operated on for primary acquired inguinal
      hernia. They underwent hernioplasty using a polypropylene prosthesis, accounting
      for 14.1% of all general surgery operations performed. The patients operated on
      were 345 males and 39 females, with an average age of 53.4 years (range: 16-91
      years). All patients were routinely subjected to ultra-short-term prophylaxis
      with antibiotics for surgical infections. In 211 cases, the operations were
      performed under local anaesthesia (in 5 of these, owing to poor tolerance of
      surgical manipulation associated with a state of agitation, the patients also
      received intraoperative pharmacological sedation in 3 cases, while a
      neuroleptoanalgesia technique was performed in the other 2); 93 cases were
      performed under general anaesthesia and 80 cases under subarachnoid anaesthesia.
      In 21 cases, the inguinal hernioplasty was associated with other operations, most
      commonly with crural hernioplasty for the treatment of a crural hernia on the
      same side as the inguinal hernioplasty. We had no intraoperative complications.
      Postoperative complications occurred in 15 cases (3.9%), 11 of which caused by
      surgical problems and 4 linked to the anaesthesia technique. Long-term follow-up
      after surgery, though fairly short on average, was carried out in 265 patients
      (69% of those operated on), and to date only one relapse has been observed.

PMID- 15152513
TI  - [Validity of the study of sentinel lymph nodes in the treatment of breast
      carcinoma].
AB  - Since it was introduced in the 1990s, axillary sentinel lymph-node biopsy has
      been rapidly and widely adopted to avoid complete axillary dissection (though
      this is still the standard procedure). The aims of the study were two-fold: (i)
      to determine the value of different techniques of sentinel lymph-node
      identification and (ii) to verify the predictive value of such procedures through
      histological examination of the sentinel lymph node and axillary dissection in
      the same patients. Both sentinel lymph-node biopsy and axillary dissection were
      performed in 230 patients with T1 and T2 (< 3 cm) carcinoma of the breast.
      Preoperative lymphoscintigraphy was able to identify the sentinel lymph node in
      97.4% of cases, but, with an intraoperative hand-held probe, it was possible to
      find the sentinel lymph node in 98.2% of cases (226/230 patients). The sentinel
      lymph node was metastatic in 49.1% of cases (111/226 patients) and negative in
      50.9% (115/226). The incidence of false-negative cases was 2.6% (2/115 patients).
      The predictive value of the sentinel lymph node was 98.7%. Finally, lymph-mode
      mapping is possible is a very high percentage of patients and therefore it is
      always advisable to use all three methods of identification together. The
      diagnostic reliability of sentinel lymph-node status is equally high. At present
      there no studies are available with a long-term follow-up to confirm these
      findings, and therefore axillary dissection is still the standard surgical
      treatment for breast cancer.

PMID- 15152514
TI  - [Surgical and endoluminal treatment of carotid stenosis: our experience].
AB  - Carotid endarterectomy and percutaneous transluminal angioplasty are known to
      prevent cerebrovascular accidents. From January 1997 to December 2002, 47
      patients (35 male, 12 female; median age: 65 years) with carotid stenosis were
      observed. Neurological accidents were reported in 89.4%, while the other 10.6%
      were asymptomatic. The operative indications for the asymptomatic patients were
      high-degree stenosis (> 70%) of the internal carotid artery and ulcerated plaques
      with a moderate degree of stenosis (50%). Preoperative investigations consisted
      in colour Doppler ultrasonography, arteriography and cerebral CT scans or NMR.
      Endarterectomy was performed in 35 patients, while the other 12 underwent
      percutaneous transluminal angioplasty. The operative mortality in the 35 patients
      undergoing surgery was 5.7% (2 cases) and perioperative strokes occurred in 3
      cases (8.6%). After 36 months, 32/35 patients (91.4%) were stroke-free, and one
      patient died as a result of a stroke. In the group of patients undergoing
      angioplasty, re-stenosis occurred in 2 cases (16.7%). Our results suggest that
      colour Doppler ultrasonography is a reliable examination for investigating the
      carotid axis and that both carotid endarterectomy and percutaneous transluminal
      angioplasty are safe procedures capable of preventing future cerebrovascular
      accidents.

PMID- 15152515
TI  - Intravascular ultrasound in the endovascular management of atherosclerotic
      peripheral occlusive disease.
AB  - This study is a retrospective analysis of the impact of intravascular ultrasound
      in addiction to conventional angiography in 36 patients with 55 stenotic
      peripheral arterial lesions treated with angioplasty and/or stenting. Before
      treatment, intravascular ultrasound imaging showed that the vessel diameter was
      underestimated with angiography in 6 cases. The correlation index between
      angiography and intravascular ultrasound measurements, however, was significant
      in 27 arterial lesions. After endovascular treatment, angiography showed 3 vessel
      dissections and no incomplete stent deployment, whereas intravascular ultrasound
      showed 15 dissections and 5 instances of stent underdeployment. If we consider
      the intravascular ultrasound data as the gold standard, the specificity of
      angiography is 100%, while its sensitivity is 56% for vessel dissection and 75%
      for stent deployment. In the follow up of the 16 patients treated for iliac
      lesions with intravascular ultrasound control, re-stenosis occurred in 5%
      (primary patency 94.7%); in a control group of 15 patients treated in the same
      period without intravascular ultrasound control, re-stenosis occurred in 15.8%
      (primary patency 83.4%, difference not statistically significant). In conclusion,
      in the peripheral arteries intravascular ultrasound is more accurate than
      arteriography in evaluating dissection and stent deployment, but the routine use
      of intravascular ultrasound in every case of iliac PTA or stenting would not
      appear justified.

PMID- 15152516
TI  - Quality of life in patients with ileal pouch for ulcerative colitis.
AB  - The improvement of surgery in the treatment of ulcerative colitis prompts us to
      consider its impact on the quality of life of the patients. Obviously, it is
      mandatory that the results after surgery should be better than the symptoms which
      elective surgery is designed to treat. A review of the literature was carried out
      on the current status of quality of life in patients with ulcerative colitis
      before and after surgery using a PubMed source. The rate of success after
      restorative proctocolectomy for ulcerative colitis is 95%. The quality of life
      after restorative proctocolectomy compared with other procedures is better,
      especially in the long term. About 90% of patients would undergo pouch surgery
      again after restorative proctocolectomy, while 53% of patients submitted to other
      procedures would have a restorative proctocolectomy. Restorative proctocolectomy
      is the gold standard for patients with ulcerative colitis who are suitable for
      surgical treatment, though future prospective trials are needed in order to
      establish when elective surgery for ulcerative colitis is indicated.

PMID- 15152517
TI  - [Operative laparoscopy in the management of perforated peptic ulcer].
AB  - The aim of this retrospective study was to assess the feasibility, safety and
      efficacy of the laparoscopic approach in the management of perforated peptic
      ulcers. From January 1997 to December 2002, all patients referred to our
      community hospital for abdominal surgical emergencies were routinely managed by
      laparoscopic surgery. A review was carried out on 39 consecutive patients
      suffering from perforated peptic ulcers with or without generalised peritonitis.
      The study population comprised 24 male and 15 female patients, aged 30 to 94
      years (mean age: 62 +/- 18). Laparoscopic repair was attempted in all patients.
      Laparoscopy afforded the correct diagnosis in all cases. Laparoscopic peritoneal
      washout (irrigation and suction of the entire abdominal cavity) with simple
      suture of the perforation proved successful in 34 patients. An additional omental
      patching was performed in 15 of these cases. Conversion to conventional open
      surgery was necessary in 5 patients. The morbidity and mortality rates were 13%
      and 10%, respectively. The mean operative time was 77 minutes (range: 40-120) and
      the mean hospital stay 9 days (range: 3-22). Laparoscopic repair of perforated
      ulcers is technically feasible but requires sound experience in laparoscopic
      abdominal emergencies. This study shows that the mini-invasive procedure is safe
      and effective, offering a valid alternative to traditional laparotomy.

PMID- 15152518
TI  - [Isolated pancreatic metastasis from kidney carcinoma: report of 2 clinical
      cases].
AB  - Isolated metastases to the pancreas are rare. Renal cell carcinoma is one of the
      few tumours that metastasis to the pancreas. Since 2001 we have observed two
      cases of isolated metastases to the pancreas from renal cell carcinomas, both of
      which were surgically resected with a diagnostic and therapeutic intent. The aim
      of this report was to examine the clinical manifestations and radiological
      appearances of these metastases through the presentation of our two cases and a
      review of the literature, in addition to assessing the respective roles of FNAB
      in the diagnostic phase and of surgery in the therapeutic phase.

PMID- 15152519
TI  - [Laparoscopic appendectomy: retrospective studies of 172 consecutive procedures].
AB  - The aim of our study was to assess the efficacy and safety of laparoscopic
      appendectomy, as performed by experienced and trainee surgeons in a Unit of
      General Surgery. From June 1997 to May 2002, 172 patients underwent laparoscopic
      appendectomy. Age below 13 years was an exclusion criterion. There was no single
      protocol for the diagnosis and surgical technique adopted by the different
      surgeons. The average operating time was 65.3 min (range: 41-106 min). There were
      9 conversions to open surgery (5.2%) and 9 postoperative complications (5.5%) out
      of a total of 162 patients undergoing the laparoscopic procedure. Oral intake was
      resumed on post-operative day 2 and the average hospital stay was 3.4 days
      (range: 3-5 days). In conclusion, laparoscopic appendectomy proved to be safe and
      effective, even when performed by surgeons with only limited experience of
      minimally invasive surgery.

PMID- 15152520
TI  - Non-iatrogenic common bile duct injury repair by Gore-Tex vascular graft: a case
      report.
AB  - The repair of common bile duct injuries is a challenge even when performed by
      experienced surgeons. Bile duct defects are normally repaired by biliodigestive
      or biliobiliary anastomoses but several experimental studies have been conducted
      with the aim of understanding whether or not synthetic prosthetic materials can
      be used. Although there are few experimental studies on the use of autogenous
      grafts, most of the international literature would appear to be more interested
      in the use of synthetic materials. The authors report their experience with non
      iatrogenic common hepatic duct injuries that, due to technical difficulties, were
      repaired by means of a pioneering technique, namely the Gore-Tex vascular graft.

PMID- 15152521
TI  - The treatment of Spigelian hernia with the Prolene Hernia System: notes on
      techniques.
AB  - Spigelian hernia repair techniques use prostheses both in the traditional and the
      videolaparoscopic approach; only in selected cases direct suturing of the
      parietal defect is performed. The aim of this study is to describe a technique
      that uses a device proposed specifically for inguinal hernias, but which has not
      yet been described in the literature, namely the Prolene Hernia System (P.H.S.).
      Our personal experience consists of 7 cases (5 females and 2 males; mean age: 58
      years) operated on from January 2002 to May 2003. Four patients were operated on
      in the ordinary hospitalisation regime with selective spinal anaesthesia and
      three patients were treated in the day surgery setting with local anaesthesia.
      With this technique, the underlay patch is positioned in an adequately prepared
      preperitoneal space and the onlay patch above the internal oblique muscle, while
      the connector acts as a plug positioned in the parietal defect. The method has
      proved simple, safe, and fast. It causes minimal discomfort to the patient in
      terms of postoperative pain and allows rapid rehabilitation. Moreover, it can
      also be performed in the day surgery setting. The authors conclude that the
      P.H.S. Spigelian hernia repair technique is a valid alternative to any of the
      other methods used to date.

PMID- 15152522
TI  - Synchronous bilateral renal tumour: a case report.
AB  - We report a case of synchronous bilateral renal carcinoma treated by partial
      nephrectomy on the right and total nephrectomy on the left. Follow-up at 42
      months after surgery showed no recurrence of the disease. The increasing use of
      diagnostic imaging techniques such as ultrasound tomography, computerised
      tomography and nuclear magnetic resonance now allows even small-sized renal
      formations to be identified. Synchronous bilateral renal tumour has a favourable
      prognosis, especially when compared with single or asynchronous renal tumours.
      The recommended intervention is total monolateral nephrectomy combined with
      partial nephrectomy. The treatment of neoplasms at a more advanced stage, of such
      a nature as to necessitate bilateral nephrectomy or chemotherapy, results in a
      significant increase in mortality. Recently, biological therapy has been proposed
      as a more promising short-term option using interferon-alpha (IFN-alpha) and
      gamma.

PMID- 15152523
TI  - Endoscopic haemostasis of lower gastrointestinal bleeding from an ileocolonic
      anastomosis constructed using a biofragmentable anastomotic ring.
AB  - We describe a case of endoscopically treated severe occult acute and chronic
      bleeding from an ileocolonic anastomosis constructed using a biofragmentable
      anastomotic ring (BAR). A 28-year-old white woman presented with two episodes of
      melaena, a 6-month history of chronic iron-deficiency anaemia and weight loss. An
      initial oesophagogastroduodenoscopy and colonoscopy failed to reveal the cause of
      bleeding, whereas a second colonoscopy demonstrated bleeding from the site of the
      BAR ileocolonic anastomosis. Endoscopic haemostasis was successfully achieved by
      means of an argon-plasma coagulator.

PMID- 15152524
TI  - [Vascular malformations: the need for a multidisciplinary treatment.
      Considerations on a clinical case].
AB  - The case reported here is a paradigm of a complex vascular malformation with a
      therapeutic approach which involved both vascular radiology and surgery. The case
      came to our attention in 1999 and consisted in a tumefaction of the left gluteal
      region in a 14-year-old female. The lesion had previously been evaluated by
      ultrasonography and magnetic resonance imaging. The lesion was described as a
      dysplastic malformation with a high vascular factor. After angiography, we
      decided to embolize the mass. A second embolization also yielded no result, and
      therefore we decided to remove the dysplasia surgically. The dysplasia, however,
      was resolved only in 2001 after a third embolization. Because of the multiple
      types of symptoms, a multidisciplinary approach is required to obtain both a
      correct classification and treatment of the vascular malformations.

PMID- 15152525
TI  - [Intestinal obstruction caused by migration of intragastric device used for the
      treatment of obesity].
AB  - The authors report a case of intestinal obstruction caused by the rupture of an
      intragastric balloon for the treatment of obesity and requiring surgical
      treatment. This unusual case shows that careful patient selection and follow-up
      are of paramount importance for successful endoscopic treatment of obesity.

PMID- 15152526
TI  - Biliary squamous cell carcinoma.
AB  - Squamous cell carcinoma of the liver, bile ducts and gallbladder is extremely
      rare. We report a case of squamous cell carcinoma of the common bile duct
      manifesting atypically without jaundice, despite its large size and proximal bile
      duct dilation. A review of the literature concerning all other squamous carcinoma
      of the biliary tract is presented including 3 other bile duct cancers, 17
      intrahepatic and 30 gallbladder cancers. Compared to the more common
      adenocarcinoma these rare biliary cancers seem to present particular clinical
      features and prognostic differences which may be important for planning
      treatment.

PMID- 15152527
TI  - Buschke-Lowenstein tumor. Successful treatment by surgical electrocautery
      excision alone: a case report.
AB  - Perianal giant condyloma acuminatum is a rare variant of condyloma acuminata and
      its therapy often proves distinctly challenging. We report on a case successfully
      treated with surgical electrocautery excision alone.

PMID- 15152528
TI  - [Gastric anisakidosis: personal experience].
AB  - Anisakidosis is a parasitic disease of the human gastrointestinal tract caused by
      ingestion of marine nematode larvae such as anisakis simplex or, rarely,
      Pseudoterranova, present in raw or undercooked fish. Frequent sites of
      involvement by anisakis are the stomach, small intestine, rarely the colon, or
      the peritoneum, liver, pancreas, lung and tonsils, anisakidosis is a self
      limiting disease; the symptoms arise 12-24 hours after ingesting raw fish and
      include nausea, diarrhoea, and severe abdominal pain, but also anaphylactic
      reactions. At the site of penetration, anisakis causes marked oedema,
      eosinophilic infiltration and granuloma formation. There are haematological
      abnormalities such as marked leukocytosis of the peripheral blood, eosinophilia,
      and positive PCR and serum antibodies to the larva's surface antigens. The
      diagnosis of anisakidosis can be made by endoscopy, radiology and US, but the
      disease is often diagnosed at surgical intervention. In the gastric form of
      anisakidosis, EGIDS has both a diagnostic role and a therapeutic one because it
      is possible to remove the worm using biopsy forceps. We report on one case of
      gastric anisakidosis, in a women, hospitalised for intense epigastric pain and
      vomiting after ingesting raw fish. She underwent gastroscopy. A worm was
      extracted from the gastric mucosa using biopsy forceps. This was followed by
      clinical improvement. The worm was identified by its macroscopic and microscopic
      characteristics as an anisakis larva. At laboratory examination, marked
      leukocytosis and eosinophilia of the patient's peripheral blood were observed 3-4
      days after ingestion of anisakis.

PMID- 15152529
TI  - [New immune system approach to pain pathology--interaction with the sensory
      system].
AB  - Recently, it is suggested that peripheric and central immune activation play
      primary role in hyperalgesia and allodynia. Non-neuronal cells that are immune
      cells in the periphery and glia (microglia, astrocyte) within the brain and
      spinal cord can drive hyperalgesic and allodynic states. Microglia and
      astrocytes, activated in response to noxious stimuli in the body tissues, in the
      peripheral nerves and also in the spinal cord, produce and release proteins
      called proinflammatory cytokines (PIC). Release of PIC from activated glia cause
      excessive release of excitatory neurotransmitters from synaptic terminals of
      primary afferent neuron and then spinal cord dorsal horn pain transmission
      neurons to become so hyperexcitable. However, in addition to this effect, PIC
      appears to interfere with the functions of the hippocampus that are involved in
      cognition, memory and mood. So PIC are important mediators of enhanced pain both
      in the periphery and in the central nervous system. As a new approach, it is
      important that this sight indicates alteration of targets in pain management.

PMID- 15152530
TI  - [Gender and pain].
AB  - Epidemiological, psychophysical and prevalence studies reveal that women have
      greater and more variable pain than men. Gender differences in pain are brought
      by genetic, physiological, anatomical, neural, hormonal, lifestyle and cultural
      factors. While women are more vulnerable to pain than men, they have more ways to
      deal with it. The clinical applicability of findings from the studies on gender
      differences in pain may lead to improve not only diagnosis but also treatment
      with various drugs and techniques.

PMID- 15152531
TI  - [Minimal invasive treatment modalities for geriatric pain management].
AB  - Geriatric pain is a significant problem in health care, because of multiple
      disease processes in this aged population their population will increase.
      Treatment options for the geriatric pain patient include pharmacotherapy,
      interventional pain management, physical rehabilitation, and/or psychological
      modalities. The most commonly employed modality for geriatric pain control is
      pharmacotherapy. However in older patients nonsteroidal anti-inflammatory drugs
      (NSAIDs) have significant side effects and are the most common cause of adverse
      drug reactions. In that reason NSAIDs should be used with caution. Opioid
      analgesic drugs are effective for relieving moderate to severe pain. If weak
      opioids were found to be ineffective in attenuating pain intensity, then
      therapeutic nerve blocks or low risk neuroablative pain procedures should be
      employed prior to recommending strong opioids. A combination of invasive
      procedures and systemic medications has the distinct advantage of reducing
      medication intake and its side effects. Currently there is very scant evidence
      that this is the best treatment option while others have thought that the
      multidisciplinary approach to geriatric pain may be the most effective.

PMID- 15152532
TI  - [Vertebroplasty].
AB  - Vertebroplasty is the polymethylmetacrilate (PMMA) injection into a vertebral
      body. It may be used for patients with compression fractures due to osteoporosis,
      metastatic tumors, or benign tumors. Vertebroplasty is performed to provide pain
      relief or to produce bone strengthening. The contraindications of the
      intervention are lack of patient consent, coagulopathy, infection, radiculopathy
      and extensive vertebral destruction. Vertebroplasty may be performed with
      transpedicular or extrapedicular approaches. The main complications are lamina
      pedicle or rib fractures, pneumothorax, and cement leakage into vessels, epidural
      space or disc.

PMID- 15152533
TI  - [The role of pain in operative strategy].
AB  - As minimally invasive surgical procedures have become widespread, postoperative
      patient comfort has also gained importance for surgeons. Unfortunately, the issue
      of pain has not received the attention it deserves. Laparoscopic operations are
      not the only means of decreasing postoperative pain, as different techniques for
      open procedures have proven to result in different degrees of pain. The degree of
      postoperative pain should take place in the selection criteria for surgical
      techniques for many diseases, as well mortality, morbidity and recurrence rates.

PMID- 15152534
TI  - [Referred shoulder pain].
AB  - Referred pain; feeling pain at a site different than the source of pain; is also
      included in cancer pain. Mechanisms and treatment of referred pain has been
      evaluated because of a case with shoulder pain rising from diaphragmatic
      irritation.

PMID- 15152535
TI  - [The effects of application of rectal naproxen on postoperative analgesia,
      sedation and morphine use in heart surgery operations].
AB  - In this study, effects and side effects of application of rectal naproxen,
      combined with patient controlled intravenous morphine analgesia, were
      investigated in the elective coronary bypass operations for postoperative pain
      control, sedation and opioid use. Following the ethical committee approval and
      individual patient self consent, 40 patients, who underwent coronary artery
      bypass surgery were included in the study. A double blind study was performed by
      administering rectal naproxen to group N (n = 20) and placebo to group P (n =
      20), at the end of the operation. Doses were repeated at the 12th hour
      postoperatively. Patient controlled intravenous morphine analgesia was performed
      to all patients for postoperative 24 hours. Postoperative pain and sedation
      levels were assessed, the side effects were noted. There was no difference
      between two groups with respect to their demographic features duration of
      surgery, extubation time and side effects (p > 0.05). With respect to group P,
      decrease in opioid use, better sedation and decrease in pain scores during both
      resting and coughing was seen in group N (p < 0.05). In conclusion, analgesia
      applied by addition of rectal naproxen to opioids achieved better pain management
      in selected patients after cardiac surgery.

PMID- 15152536
TI  - [The effects of sufentanil and remifentanil in the isolated perfused rat kidney].
AB  - In this study, the effects of indomethacin (prostaglandin synthase inhibitor),
      propranolol (beta adrenergic receptors blocker), tetraethylammonium (TEA)
      (calcium-dependent potassium channel blocker) and glibenclamide (ATP-sensitive
      potassium channel blocker), NG nitro-L-arginine (NO synthetase inhibitor) and
      naloxane (nonselective opioid receptor antagonists) on the responses induced by
      sufentanil and remifentanil were investigated in the isolated perfused rat
      kidney. Renal arter was cannulated. Then the kidney was perfused continuously
      with warmed (37 degrees C) and aerated (95% O2 and 5% CO2). Krebs Henselieit
      solution by using a peristaltic pump delivering a constant flow (8-10 ml/min).
      Vascular responses were detected as changes in perfussion pressure, which was
      monitored continuously with a pressure transuder and recorded on polygraph. After
      phenilephrine (PE)-induced vasoconstriction had reached a platoe, sufentanil or
      remifentanil were given. Vasodilatation was recorded. Antagonists or inhibitors
      were added and responses were recorded. At the end of each experiment; papaverine
      was used to obtain the maximum dilatation. None of the used antagonists or
      inhibitors were not effected the submaximum PE construction. The used opioids
      were not alter in basal perfusion pressure. Antagonists or inhibitors had no
      effect on papaverine-induced dilatation. Bolus addition of sufentanil and
      remifentanil produced concentration dependent vasodilation. Indomethacine L-NAME,
      propranolol, naloxone and glibenclamide did not significantly alter responses of
      both of the opioids (p > 0.05). But, sufentanil and remifentanil induced
      dilatation were significantly affected by TEA (p < 0.05). The present results
      demonstrated that sufentanil and remifentanil decrease perfusion pressure in the
      isolated rat kidney and such mechanism may involve the calcium active K+ channels
      activation.

PMID- 15152537
TI  - Physicians and medicine in an evolving society: the role of the medical school.

PMID- 15152538
TI  - Conventional MRI, DWI and MR-spectroscopy in the study of focal brain lesions.
AB  - A case of a patient with neurologic symptoms is reported. Baseline MRI findings
      were inconclusive to establish a definitive diagnosis. The worsened neurologic
      and neuroradiologic pattern directed towards a diagnosis of tumor. A second MRI
      examination and MR-spectroscopy confirmed the hypothesis based on both the
      diagnosis of nature of the lesion and the histological characterization of the
      surgical specimen. The technique of MR-spectroscopy is briefly described.

PMID- 15152539
TI  - Diagnostic imaging and therapy in a case of myasthenia gravis associated with
      thymic hyperplasia.
AB  - The diagnostic approach to a patient with myasthenia gravis to verify the
      presence of thymic hyperplasia/thymoma is presented. The study of the mediastinal
      region was necessary. Mediastinal MRI showed the presence of a mass. The
      differential diagnosis between a mediastinal and an extramediastinal lesion is
      possible with MRI for its high contrast resolution, good spatial resolution and
      multiplanarity that allow the detection, localization, evaluation of the extent
      and/or infiltration of adjacent tissues/organs based on the analysis of adipose
      cleavages and typing in the different pulse sequences of pathologic tissue with
      contrast enhancement. Definitive diagnosis of thymic hyperplasia was established.
      Therefore surgery should be essentially associated with the severity of the
      clinical presentation rather than with thymic hyperplasia.

PMID- 15152540
TI  - Suspected cup syndrome. Diagnostic imaging of a misunderstood breast tumor for
      its uncommon location.
AB  - The case of a 41-year-old female patient with axillary lymphadenopathies and
      negative clinical and mammographic examinations is discussed. In the suspicion of
      a cup syndrome of breast origin, breast sonography was performed. While the
      absence of alterations was confirmed, a right parasternal swelling was highly
      suggestive of malignancy. On histology, a malignant parasternal nodule was
      diagnosed. Breast MRI was performed and an ipsilateral malignant focal lesion was
      visualized. Chemotherapy was administered but after a disease-free interval
      leptomeningeal and cerebral metastases appeared.

PMID- 15152541
TI  - A reasoned approach to a case of suspected arteriovenous fistula.
AB  - The case of an 82-year-old female patient with severe tricuspid regurgitation
      come to the authors' observation for suspected arteriovenous fistula, is
      reported. Color-Doppler US was performed for re-evaluation. It documented the
      presence of systemic venous and portal pulsatility associated with severe ectasia
      and varicosity of infracardiac systemic venous system due to systemic venous
      hypertension. Color-Doppler study allowed a correct diagnostic approach,
      excluding the presence of an arteriovenous fistula.

PMID- 15152543
TI  - Combined diagnostic imaging of adenomyomatosis of the gallbladder.
AB  - The consistency of a request for liver MRI and MR-cholangiopancreatography in a
      patient with an occasional US-finding of mural thickening of gallbladder fundus >
      or = 3 mm in size was assessed. The differential US diagnosis in case of focal
      mural thickening was analyzed in combination with the other findings to justify
      the radiologicoclinical reliability of the request. Overall, these findings
      suggested the diagnostic hypothesis of adenomyomatosis, then confirmed by a
      second level in-depth examination, namely liver MRI and MR
      cholangiopancreatography.

PMID- 15152542
TI  - Diagnostic imaging of the digestive tract. Reasoned approach to a duodenal
      filling defect.
AB  - A case of a patient with sideropenic anemia of suspected gastrointestinal origin
      is presented. A radiologic study of the upper digestive tract was performed. It
      documented a duodenal filling defect giving rise to an analytic discussion
      throughout various perceptive-interpretative logical steps: the image reality,
      the formation of the filling defect image and its nature. The radiologist's
      conclusions supported the presence of a benign submucosal neoformation to be
      treated with surgical resection for its size and for the patient's clinical
      conditions.

PMID- 15152544
TI  - Intestinal lymphangiectasia.
AB  - The case of a 26-year-old female patient with abdominal pain, nausea,
      hypoproteinemia, enteric loss of plasma proteins, lymphedema, severe steatorrhea
      and malabsorption, is presented. Enteroclysis and sonography were performed.
      Based on the case history and the characteristics of focal lesion and intestinal
      folds provided by the two radiologic examinations, a specific diagnosis of
      intestinal lymphangiectasia, confirmed at biopsy, could be established.
      Intestinal lymphagiectasia is a very uncommon condition characterized by dilated
      submucosal lymphatic channels.

PMID- 15152545
TI  - Combined diagnostic imaging of transitional cell carcinoma of the upper urinary
      tract.
AB  - The case of a female patient with recurrent macroscopic hematuria and negative
      vesical and renal ultrasonography, is discussed. On urography a gross
      pyelocaliceal filling defect was visualized. Urographic findings were suggestive
      of the diagnosis of transitional cell carcinoma of the upper urinary. CT was
      performed to confirm the diagnosis and stage the tumor: it showed the presence of
      an advanced lesion. At histology the diagnosis of transitional cell carcinoma of
      the upper urinary tract was confirmed.

PMID- 15152546
TI  - Diagnostic imaging of the small bowel in a case of occult gastrointestinal
      bleeding.
AB  - A case of a male patient with occult gastrointestinal bleeding and negative
      gastroscopy and colonoscopy is presented and discussed. Oral small bowel barium
      follow-through was performed upon the patient request. It documented a jejunal
      neoformation. The analysis of radiologic findings directed towards a probably
      extramucosal origin. Subsequent CT evaluation confirmed a neoformation
      inseparable from a jejunal loop with inhomogeneous contrast enhancement,
      therefore of suspected malignant nature. The histological examination on the
      surgical specimen documented the presence of a stromal tumor of indeterminate
      malignancy.

PMID- 15152548
TI  - [Ethical problems of biomedical research in occupational medicine].

PMID- 15152547
TI  - Diagnostic imaging of the diabetic foot. What the clinician expects to know from
      the radiologist....
AB  - A case of diabetic foot in a patient with advanced diabetes is presented. The
      correct diagnostic approach was analyzed based on the reasoned combination of
      available diagnostic imaging procedures (color-Doppler US, CT-angiography, MR
      angiography and digital subtraction angiography) and on the clinician's
      instances. Angiographic findings contraindicated intravascular treatment.
      Femorotibial surgical bypass was performed.

PMID- 15152549
TI  - [Reproductive health of women in rural areas of Ukraine].
AB  - The authors revealed age and occupation related features of reproductive health,
      determined the risk factors and specified the prophylactic measures.

PMID- 15152550
TI  - [Assessment of workplace pollution with furadan during centalized treatment of
      sugar-beet seeds and recommended protective means].
AB  - Having evaluated work conditions in sugar-beet seeds treatment with furadan, the
      authors justified use of an individual protective means for the workers. The
      recommendations are coveralls of nonwoven materials like Tyvek F, C that are
      resistant against concentrated and working solutions of furadan. To protect
      respiratory organs against furadan vapors and aerosols, one should use respirator
      of sorption filter half mask.

PMID- 15152551
TI  - [Effect of work conditions on life expectancy in workers of some occupations
      (methodological approaches)].
AB  - The authors presented methodic approaches to evaluation of work conditions
      influence on average life expectancy in workers of some occupations.

PMID- 15152552
TI  - [Gene polymorphism of xenobiotics in workers of petroleum and chemical industry].
AB  - Increasing use of aromatic hydrocarbons and their derivatives, known mutagens and
      carcinogens, in petrochemistry leads to higher number of workers having
      occupational contact with those chemicals. Most alien chemicals (xenobiotics)
      incorporated into human body do not demonstrate direct biological effects but
      undergo various biologic transformations. Humans proved to have genetic control
      over metabolism of xenobiotics entering the body, so various individuals
      depending on genetic features could be resistant or otherwise be extremely
      sensitive to chemical agents.

PMID- 15152553
TI  - [Studying of oxidative metabolism in occupational medicine (review of
      literature)].

PMID- 15152554
TI  - [Hygienic characteristics of biologic factors in the production of mixed fodder
      (review of literature)].

PMID- 15152555
TI  - [Effect of biological preparation alfetin in infiltrative pulmonary
      tuberculosis].
AB  - The authors evaluated influence of Alfetin new Russian biologic preparation on
      pulmonary surfactant system and phospholipid metabolism in workers at risk of
      occupational pneumoconiosis, who suffer from infiltrative pulmonary tuberculosis.
      Considering positive changes in serum phospholipids subunits under alfetin
      treatment, the authors proved membrane protective effect of the drug. Alfetin was
      proved to weaken toxic effects of tuberculostatic drugs on lung surfactant.

PMID- 15152556
TI  - [Ischemic heart disease in fluorosis].

PMID- 15152557
TI  - [Provision of electromagnetic safety for radio broadcasting information systems].

PMID- 15152558
TI  - [Electric and magnetic fields shielding for high-voltage airborne power lines].

PMID- 15152559
TI  - [Changes in biochemical and immunological parameters in humans exposed to
      organosilicon compounds].

PMID- 15152560
TI  - [Changes in biological rhythms of workers in the fluorine manufacturing
      industry].

PMID- 15152561
TI  - [Medical and social characteristics of patients with chronic obstructive
      pulmonary diseases].

PMID- 15152562
TI  - [Individual dynamics of the EEG running wave under various conditions of
      activity].
AB  - In 25 healthy subjects at resting with their eyes closed and open, a current
      phase structure of the EEG was measured, i.e. a trajectory and velocity of
      oscillation spreading over the head surface in temporal-occipital area. Visual
      computer multiplication revealed stable individual specifics of the EEG "running
      wave" dynamics which were then confirmed independently proceeding from the
      statistical significance criteria. Some subjects had characteristic transversal
      modulations of the EEG waves (from the left fo the right and vice versa), other
      subjects manifested longitudinal modulations along the diagonal from the cortex
      left anterior areas to the right posterior those (in some of them) or along the
      same diagonal in the opposite direction (in others). When opening the eyes, the
      character of the EEG "running wave" undergoes dramatic changes. Among other
      parameters, a growth of the trajectory share occurs in occipital area along with
      acceleration of the "running wave" spreading on all other trajectories. Both
      effects are bound to each other and the sharper dynamics is specific for subjects
      characterised as sympathotonic those as compared with para-sympathotonic.

PMID- 15152564
TI  - [Potential mechanisms of effects of endogenous neuromodulators on the
      interdependent activity of neurons in various nuclei of the basal ganglia].
AB  - A possible mechanism of influence of neuromodulators on interdependent activity
      of neurons in the diverse basal ganglia nuclei is suggested. According to
      modulation rules, an activation of postsynaptic Gs- or Gq/11-(Gi/0-) protein
      coupled receptors promotes induction of long-term potentiation (depression) of
      excitatory inputs to different neurons and augmentation (lowering) of their
      activity; an activation of presynaptic Gs- or Gq/11-(Gi/0-) protein coupled
      receptors promotes a rise (decrease) of release of GABA and co-peptides from
      striatal terminals and glutamate release from subthalamic terminals in the globus
      pallidus and output nuclei. It follows from the modulation rules that, since
      identical receptors are present on striatal neuron and their axon terminals,
      effects of neuromodulator action in diverse basal ganglia nuclei can be
      summarized. Neuromodulators released from striato-nigral and striato-pallidal
      fibers could promote interdependent activity of neurons in "direct" and
      "indirect" pathways through the basal ganglia due to convergence of these fibers
      on cholinergic interneurons and pallido-striatal cells.

PMID- 15152563
TI  - [Electroconvulsive shock causes neuronal death in the mouse hippocampus:
      correlation of neurodegeneration and convulsive activity].
AB  - Relations between seizures induced by repeated electroshock (ES) and structural
      changes in the hippocampus were investigated in Balb/C mice. Brain sections of
      the animals 2 or 7 days after the last ES were stained for Nissl or TUNEL
      (apoptotic nuclei). Direct measurement of caspase-3 activity (a key enzyme of
      apoptosis) in brain regions was performed immediately after the last ES.
      Statistically significant, albeit moderate cell loss was demonstrated in the CA1
      field and dentate gyrus, but not in the CA3 field of the hippocampus. The number
      of neurons in these fields inversely correlated with seizure severity. No
      apoptotic nuclei could be revealed either in hippocampus or in other brain
      regions. Caspase-3 in the hippocampus decreased after ES. The data obtained
      support the results from other groups showing prominent functional changes in
      neurons induced by repeated ES and extend this concept directly testifying for a
      moderate (within 10%), albeit statistically significant neuronal death in
      selected hippocampal fields. The inverse correlation of cell number with severity
      of seizures suggest that these are seizures inducing neuronal death.

PMID- 15152565
TI  - [Characteristics of the EEG power and coherent structure of term and premature
      children during the first postnatal year].
AB  - Objective of the study involved characteristics of the spectre of the EEG power
      and coherent structure in children of different degree of maturity in the first
      month of their postnatal development. 32 children were divided into three groups:
      1) 38-41 weeks (11 children); 2) 34-36 weeks (12 children); 3) 30-33 weeks (9
      children). At the moment of the study the children's chronological age was as
      follows: in the 1st and 2nd groups--19 +/- 1, in the 3rd group--30 +/- 4 days. In
      the 1st group (mature children), a considerable power of delta- and theta-range
      frequencies was registered as compared with the 2nd and 3rd groups. In the 1st
      group children, a central gradient of power of the delta and theta frequencies
      was noted as well as a central-occipital one for alpha-frequencies. In the 2nd
      group (34-36 weeks), a lesser power of the delta-, theta- and alpha-frequencies
      was noted as well as a smoothed central gradient of these frequencies as compared
      with the 1st group. In the 3rd group, the power of delta-frequencies in frontal
      leads and power of alpha-frequencies in most EEG leads did not differ from those
      in the 1st group, and an obvious frontal gradient of delta-frequency power was
      noted as well as the frontal-central one for the theta- and alpha-frequencies. In
      all the groups, three foci of coherent interaction among the brain areas were
      registered: anterior, central and posterior. The coherence of biopotentials was
      registered on the frequencies of delta-, theta- and alpha-ranges. The maximum
      level of coherence was registered in the delta-range. In immature children, as
      compared with mature ones, a higher level of coherence was registered in the
      theta- and alpha-frequencies.

PMID- 15152566
TI  - [Changes in response latencies of the mouse inferior colliculus neurons depending
      on the position and movement direction of the spectral contrast].
AB  - Variability of response latency of neurons in the mouse inferior colliculus of
      (Mus musculus) to signals of notch noise and of noise band with regular varying
      of the notch/band center frequencies, have been studied. Plots of latency and
      spike count versus notch/band center frequency were constructed (latency
      functions and spike count functions). Spectral notch/noise band motion crossing
      boundaries of excitatory areas in the neurons frequency receptive field could
      produce latency function shifts (and appropriate to this spike count function
      shifts). Direction-dependent latency function and spike count function shifts
      were mostly seen for primary-like and V-shape neurons. The most interesting
      feature of directional sensitivity of inhibitory-dominated neurons was the
      selective shortening of latency and selective synchronization of the initial
      spikes (with appropriate to this spike count rise). The dynamic properties of
      inhibitory-dominated neurons can be explained on the basis of their selective
      sensitivity to position of spectral contrast in frequency receptive field,
      connected with disinhibition, and of the character of distribution of excitatory
      and inhibitory inputs. Manifestation of motion effects was influenced by spectral
      shape of noise signal and notch width.

PMID- 15152567
TI  - [Functioning of the electromechanical connection in the course of the contracture
      contraction].
AB  - The effects of calcium release blocker dantrolene was tested on electrically
      evoked twitches and on contractures induced by potassium depolarization, by
      acetylcholine or caffeine. It was shown that the first: developmental, stage of
      potassium or acetylcholine contracture is inhibited by dantrolene and is not
      influenced by calcium free medium, therefore we may interpret it as based on a
      "voltage-dependent Ca release" (VDCR) mechanism of activation, whereas
      depolarization directly opens the rhyanodin receptor calcium channels. On the
      contrary, the next stage: the long-lasting plateau of contracture, is directly
      dependent on external Ca2+ and inhibited by dantrolene, and therefore can be
      described as "calcium induced Ca-release" (CICR) activation mechanism. In this
      case stored calcium is also released by rhyanodine receptors, although by means
      of entering the extracellular Ca2+. Finally, the last stage of low amplitude is
      not influenced by dantrolene nor by calcium-free medium. Therefore the activation
      of contraction on this stage is not based on the Ca2+ release through the
      rhyanodin receptor calcium channels.

PMID- 15152568
TI  - [Effect of personality traits on levels of lipid peroxidation products in serum
      and the blood antioxidant activity].
AB  - Psychometris evaluation of personality traits and subsequent laboratory study of
      lipoperoxidation products in blood serum and its antioxidative activity were
      performed in 27 healthy volunteers. Data obtained suggest that personality traits
      determinate to a certain extent the lipoperoxidation and blood serum
      antioxidative activity.

PMID- 15152569
TI  - [Neuronal interaction at the cell body level in the snail CNS. Neuroactive
      environment heterogeneity].
AB  - In experiments on Lymnaea stagnalis, a single neuron isolated from the PeA
      cluster was used as moveable sensor for monitoring extracellular environment of
      the CNS surface. At the serotoninergic PeA area, two novel neuroactive factors
      were detected: inhibitory and excitatory ones. The former is transiently released
      whenever extracellular 5-HT increases. A distinctive feature of the latter is
      that it narrows the action potential of the sensor cell. The findings demonstrate
      that natural neuro-active factors occur in the soma vicinity in effective
      concentrations, thus suggesting that, in the snail brain, activity of central
      neurons is controlled by neurotransmitters operating at the cell body level.

PMID- 15152570
TI  - [Long-term isolated housing causes anxiety in C57BL/6J female mice].
AB  - Behaviour of female C57BL/6J strain mice was studied in the elevated plus-maze
      and Porsolt's tests after either long-lasting individual housing or keeping with
      daily shifting group-housed females (social instability). After 2-3 months, an
      increased level of anxiety in the individually housed females was revealed in the
      elevated plus-maze. However, in 3 months the least passive behaviour in the
      Porsolt's was in the individually housed females. No changes were found in
      behaviour of females individually housed at 3 weeks of age for 4 months. Also,
      females with preliminary social contacts with males and following individual
      housing for one month had not any abnormalities in the used behavioural tests.
      Social instability conditions did not significantly influence the females' plus
      maze behaviour, but decreased the passive behaviour in the Porsolt's test.

PMID- 15152571
TI  - [Different responses of DD/He and CC57BR/Mv mice to fasting].
AB  - Reaction to fasting of 2 mice strains differing in their sensitivity to
      spontaneous and induced hepatocarcinogenesis, has been investigated. It was shown
      that mice of both strains displayed similar stress reaction after 3-day fasting
      manifested in increase in blood corticosterone level; and decrease in
      testosterone level. At the same time, both strains demonstrated opposite changes
      at tissue- and enzyme levels in the liver. It was shown that DD/He mice, highly
      sensitive to induction of liver tumors, were characterized by significant
      increase in tyrosine aminotransferase (TAT) activity and reduction of lipid
      droplets in hepatocytes. CC57BR/Mv mice, demonstrating high frequency of
      spontaneous hepatomas and insensitive to induction of such tumors, were
      characterized by a decrease in the TAT activity and fatty infiltration of the
      liver.

PMID- 15152572
TI  - [Carbachol effect on kinetics of the alpha1-adrenergic contractile response of
      the rat vas deferens].
AB  - Analysis of the control kinetics of the rat vas deferens contractile response to
      phenylephrine showed that alpha 1-adrenoceptors mediating the contraction could
      be in different functional states. In some organs these receptors represented a
      single pool with Hill coefficient n = 1 (the linear mode of the Scatchard plot),
      in others--not a single pool, n > 1 (not linear mode of the Scatchard plot).
      Activation of muscarinic cholinergic receptors by carbachol exerted a stimulating
      effect on the alpha 1-adrenergic contractile response especially to low
      adrenomimetic concentrations and the maximum response was increased. The action
      of cholinomimetic was accompanied by a decrease of Hill coefficient. When the
      control represented a single pool of alpha 1-adrenoceptors in the presence of
      carbachol Scatchard plot became biphasic with Hill coefficient n < 1, in addition
      to the low affinity pool the high affinity appeared. In case of not homogeneous
      control pool, in the presence of carbachol a single pool was revealed and n was
      close to 1. These findings suggest that the stimulatory effect of carbachol is
      caused by its modulator action on the alpha 1-adrenoceptors states and activating
      influence on the intracellular effector's system.

PMID- 15152574
TI  - Tobacco cessation. Good reasons to quit.

PMID- 15152573
TI  - [Age-related specifics of aldosterone reception in distal segments of the rat
      nephrons and of Na(+), K(+)-ATPase expression induction].
AB  - The reason of unresponsiveness of young 10-day rats kidney to aldosterone was
      explored. The aldosterone binding in distal segments of renal nephrons and the
      influence of hormonal induction on the mRNA of the alpha and beta subunits of the
      Na+, K(+)-ATPase in 10-day and 2-month old rats were investigated. There was no
      age related difference in the aldosterone specific binding in presence of RU
      38486 (10(-7) M; Russel Uclaf) in the cortical collecting tubules: 0.26 +/- 0.04
      (n = 9) and 0.22 +/- 0.03 (n = 8) mMol/mm of tubule lengths in 10 day and adult
      rats, respectively. By Nozern blot analysis and RT-PCR more then three and two
      fold increase of the mRNA abundance of both subunits was found in young and adult
      renal cortex compare to the adrenalectomized control after aldosterone induction
      (5 micrograms/100 g. v. b. w. 4 times i/p injections in 3 hour interval between
      injections) (p < 0.01). By RT-PCR no expression of the alpha 2, alpha 3 and beta
      2 isoforms has been observed in all experimental conditions. The age difference
      was discovered when aldosterone was injected together with spironolactone (5
      micrograms and 12 mg per 100 g. b. w. respectively). It was shown, that
      spironolactone inhibits the effect of aldosterone in adults whereas the latter
      was unaffected in young rats. The scheme of the age-related differences in the
      aldosterone regulation of the sodium pump induction in the target cell of the
      distal part of the rat nephrons is presented.

PMID- 15152575
TI  - Brief advice to help dental patients quit smoking.

PMID- 15152576
TI  - Pay attention to patients' tobacco use to avoid malpractice claims.

PMID- 15152577
TI  - Role of dentists in tobacco cessation programs.

PMID- 15152578
TI  - Benchmarking and safety: natural fit if you know what to do with data.
AB  - Know what you want to benchmark, what your goals are, and why. Interpreting your
      data properly is one of the biggest challenges. Experts complain of the dearth of
      national benchmark standards.

PMID- 15152579
TI  - Six Sigma success: 100% compliance in 3 months.
AB  - Success demonstrates applicability to improving clinical performance. The define
      measure-analyze-improve-control methodology is critical to impact of the program.
      Savings in single service line now are spreading to entire system.

PMID- 15152580
TI  - Hospitalists save $2.5 million and decrease LOS.
AB  - Hospitalist program helps readmission rates also decline; satisfaction rates
      rise. Unassigned patients had caused problems in decision making and follow-up.
      Other hospitalist programs were benchmarked before partner was chosen.

PMID- 15152581
TI  - AHRQ tool designed to improve CAP clinical care.
AB  - Tool helps docs decide whether to hospitalize community-acquired pneumonia
      patients. Pneumonia Severity Index clinical algorithm developed by AHRQ team.
      Agency hopes to develop several more similar tools.

PMID- 15152582
TI  - Leapfrog standards are hard for hospitals to meet.

PMID- 15152583
TI  - Visceral pain.
AB  - Visceral pain, which originates from organ tissues of the thorax, abdomen or
      pelvis, is generally perceived as a deep, dull and vague sensation; in most cases
      it cannot even be clearly described, being a sense of discomfort, malaise or
      oppression rather than real pain. Crushing, cutting and burning generally have no
      algogenic effect in the viscera whereas mechanical stimulation, ischemia and
      chemical stimulation, separately or in combinations, may cause pain. With these
      characteristics, visceral pain differs from somatic pain. The characteristics of
      visceral pain, perception and transmission of painful visceral stimuli are
      explained, some common visceral pain syndromes are presented and sympathetic
      neurodestructive approaches as a treatment option are described in this review.

PMID- 15152584
TI  - [Methods for assessment of pain in children].
AB  - In children, assessment and measurement of pain is challenging. The difficulties
      of pain assessment in children can be explained by their constantly changing
      state of perception, interpretation and expression of pain related to age,
      developmental stage, previous pain experiences, and other modifying environmental
      factors. Unlike most adults, children (especially younger ones) lack the
      cognitive and behavioral competency both to understand questions concerning their
      pain and to describe their pain. Especially very young children don't have pain
      experience and cooperation with adults is limited. Age, general health status and
      ability of self report are the factors that must be considered when selecting
      appropriate method of pain measurement and pain assessment must be repeated
      regularly. Although many different tools are used to measure and assess pain, no
      single one supplies enough information about pain and its different components to
      be used as the standard measure of pain in children.

PMID- 15152585
TI  - [Regional anesthesia and analgesia applications in children and infants--II].
AB  - For years pediatric pain management has been practiced without clear rational use
      of analgesic therapy. The recent improved understanding of anatomical and
      physiological pathways of pain perceptions, and opioid and local anesthetic
      pharmacology in infants and children has led to the development of formal
      analgesic regimens for the management of pain. Also modifying the anatomical
      approach for children, studying new agents and combinations of agents,
      technological developments have made regional anesthetics techniques more
      accessible to children. For these reasons, in the last two decades, there has
      been an explosion of interest and research related to the use of regional
      anesthetic techniques in children. Regional anesthetic techniques have a
      significant but limited place in the practice of pain management in infants and
      children. However regional anesthetic techniques presumably afford many of the
      same advantages for the pediatric patients as it does in the adult patients. In
      this review, we discuss regional and topical anesthetic techniques available to
      clinicians who care for this population.

PMID- 15152586
TI  - Radiofrequency lesioning of the sympathetic chain at different levels.
AB  - The interruption of sympathetic pathways is a commonly used modality for the
      treatment of many painful conditions and some other problems like vascular
      disorders. Radiofrequency (RF) techniques have gained popularity in this field in
      the recent years. The major advantages of RF techniques over other
      neurodestructive methods are; the formation of controlled lesion, low
      complication rates and low perioperative discomfort. In this paper, RF
      applications of the different sympathetic regions are described, together with
      the indications, risks and comments of the author.

PMID- 15152587
TI  - [Thalamic pain syndrome].
AB  - Central pain is a chronic pain due to various causes, with accompanying
      neurological symptoms and often unresponsive to medical therapy. Pain management
      and results in a 31 years old female patient with a diagnosis of thalamic pain
      syndrome, which is one of the causes of central pain is analysed in this article.

PMID- 15152588
TI  - [Pott disease in the differential diagnosis of low back pain].
AB  - Tuberculosis of skeletal system is frequently located in spine and is called as
      "Pott disease". Pott disease is frequently located in lumbar vertebrates and it
      can be interfered with the other diseases which cause low back pain. Our patient
      which was operated because of breast cancer nearly 10 years ago, has had waist
      and leg pain for 6 weeks. The story of breast cancer reminded us the possibility
      of a metastasis. But there were no findings in favour of metastasis except the
      high scores of sedimentation rate. There was a disc herniation according to the
      MR imaging of lumbar region. Therefore we performed epidural steroid injection
      but 10 days later the patient was unable to walk. We present this case to
      understand the importance of the differential diagnosis of Pott disease.

PMID- 15152589
TI  - [Is epidural preemptive analgesia effective in lower abdominal surgery?].
AB  - In this study, we aimed to investigate the preemptive analgesic efficacy of
      epidural application of fentanly-bupivacaine combination. A total of 60 patients
      admitted for total abdominal hysterectomy were included in this study after the
      approval of the ethic committee, and the patients were randomly classified into
      three groups. An epidural catheter was inserted to all patients through L2-3 or
      L3-4 space before general anesthesia induction. 2 micrograms/kg fentanyl in 0.25%
      bupivacaine in 10 ml serum saline was applied to the preemptive analgesia group
      (Group P) 20 minutes before the incision, and to the post-incisional analgesia
      group (Group E) 20 minutes after the incision, whereas control group received 10
      ml serum saline 20 minutes before the incision through the epidural catheter.
      Pain scores were assessed with 100 mm Visual Analogue Scale (VAS) and four point
      Verbal Rating Scale (VRS) at 1., 2., 4., 6., 12., 24., 48. hours postoperatively.
      First analgesic requirement time and total analgesic consumption for 48 hours
      were also recorded. The VAS and VRS values in the postoperative 48 hours were
      significantly lower in Group P compared with the other groups (p < 0.05). First
      analgesic requirement time was also significantly prolonged in Group P (p <
      0.001). Total analgesic consumption in Group P was significantly lower than the
      other two groups (p < 0.05). As a result we observed that preemptive
      administration of epidural fentanyl-bupivacaine combination reduces the
      postoperative pain and analgesic consumption in lower abdominal surgery.

PMID- 15152590
TI  - [Evaluation of the knowledge and attitude of obstetric patients on epidural
      analgesia].
AB  - Epidural analgesia (EA) is one of the most commonly used techniques in obstetric
      analgesia. Our objective was to evaluate patients who experienced EA during
      labour as well as to find out their knowledge, attitude and behaviour in this
      matter, prospectively. Between 1997 and 2002, a questionnaire, "patient
      evaluation form for EA", was delivered to 190 obstetric patients. The patients
      were divided into two groups. In Group I there were 100 patients who were
      evaluated between 1997 and 1999, and Group II was comprised of 90 patients who
      were evaluated between 2000 and 2002. Demographic data of the patients were
      similar in both groups. The question "How have you been informed about EA?" was
      replied as "TV or newspaper" by 50% of the patients in Group I while the answer
      was "from someone who experienced it before" by 60% of the patients in Group II
      (p < 0.01). With these information about EA, 30% and 40% of the patients in Group
      I were found out to be worried about neural paralysis and some possible disorders
      related to their babies, respectively. However, 40% of the patients in Grup II
      worried about back pain and headache (p < 0.01). As a result, considering the
      mother candidates' high information rate from someone who experienced EA before
      (60%), interest to the labour analgesia will increase as the mothers are
      satisfied with the results of EA.

PMID- 15152591
TI  - Life science applications of nanotechnology.

PMID- 15152592
TI  - Modification of the enzyme mismatch cleavage method using T7 endonuclease I and
      silver staining.

PMID- 15152593
TI  - Cloning independent site-directed mutagenesis using total RNA as template.

PMID- 15152594
TI  - Improved siRNA-mediated silencing in refractory adherent cell lines by detachment
      and transfection in suspension.

PMID- 15152595
TI  - RAPD analysis of mtDNA from tomato flowers free of nuclear DNA artifacts.

PMID- 15152596
TI  - Tandem immunoaffinity purification of protein complexes from Caenorhabditis
      elegans.

PMID- 15152597
TI  - Three new Drosophila markers of intracellular membranes.
AB  - The need for cellular markers that permit a quick and accurate evaluation of a
      protein's subcellular localization has increased with the surge of new data
      generated by the Drosophila genome project. In this report, we present three
      ubiquitously expressed Drosophila transgenes that expressed a green fluorescent
      protein variant (enhanced yellow fluorescent protein) that has been targeted to
      different intracellular membrane targets: the Golgi apparatus, mitochondria, and
      endoplasmic reticulum. These markers serve as an internal standard for
      characterizing a protein's subcellular localization or as a means of tracking the
      dynamics of intracellular organelles during normal or abnormal cellular or
      developmental processes. We have also examined fixation artifacts using these
      constructs to illustrate the effects that fixation and permeabilization have on
      intracellular membrane organization.

PMID- 15152598
TI  - Microarray results improve significantly as hybridization approaches equilibrium.
AB  - Dual-channel long oligonucleotide microarrays are in widespread use. Although
      much attention has been given to proper experimental design and analysis
      regarding long oligonucleotide microarrays, relatively little information is
      available concerning the optimization of protocols. We carried out a series of
      microarray experiments designed to investigate the effects of different levels of
      target concentration and hybridization times using a long oligonucleotide
      library. Based on principles developed from nucleic acid renaturation kinetics
      studies, we show that increasing the time of hybridization from 18 h to 42 h and
      66 h, especially when lower than optimal concentrations of target were used,
      significantly improved the quality of the microarray results. Longer
      hybridization times significantly increased the number of spots detected, signal
      to-noise ratios, and the number of differentially expressed genes and
      correlations among replicate arrays. We conclude that at 18 h of incubation,
      target-to-probe hybridization has not reached equilibrium and that a relatively
      high proportion of nonspecific hybridization occurs. This result is striking,
      given that most, if not all, published microarray protocols stipulate 8-24 h for
      hybridization. Using shorter than optimal hybridization times (i.e., not allowing
      hybridization to reach equilibrium) has the consequence of underestimating the
      fold change of differentially expressed genes and of missing less represented
      sequences.

PMID- 15152599
TI  - Method for systematic targeted isolation of homologous cDNA fragments in a
      multiplex format.
AB  - In this study, a two-step method for systematic multiplex cloning of homologous
      cDNAs from related species was developed. The first step, called MUCH (multiplex
      cloning of homologous genes), is cloning of partial but authentic cDNA fragments
      of homologous cDNAs by hybridization to arrayed cRNA probes of specified genes on
      a nylon membrane, followed by PCR amplification of the hybridized fragments. The
      second step is PCR-based screening of a library that contains longer cDNA inserts
      based on the sequences obtained in the first step. To evaluate this method, we
      tried to isolate mouse counterparts of 53 human large cDNAs by MUCH and could
      successfully isolate 32 mouse counterpart cDNAs from a single library. Complete
      sequencing of two mouse cDNAs isolated by PCR-based screening further
      demonstrated that this method enabled us to isolate multiple homologous cDNAs in
      parallel. We thus expect that this method could be applied to high-throughput
      cloning of homologous cDNAs in related species.

PMID- 15152600
TI  - Improved extraction of PCR-quality community DNA from digesta and fecal samples.
AB  - Several DNA extraction methods have been reported for use with digesta or fecal
      samples, but problems are often encountered in terms of relatively low DNA yields
      and/or recovering DNA free of inhibitory substances. Here we report a modified
      method to extract PCR-quality microbial community DNA from these types of
      samples, which employs bead beating in the presence of high concentrations of
      sodium dodecyl sulfate (SDS), salt, and EDTA, and with subsequent DNA
      purification by QIAamp columns [referred to as repeated bead beating plus column
      (RBB + C) method]. The RBB + C method resulted in a 1.5- to 6-fold increase in
      DNA yield when compared to three other widely used methods. The community DNA
      prepared with the RBB + C method was also free of inhibitory substances and
      resulted in improved denaturing gradient gel electrophoresis (DGGE) profiles,
      which is indicative of a more complete lysis and representation of microbial
      diversity present in such samples.

PMID- 15152601
TI  - Nondestructive DNA extraction method for mitochondrial DNA analyses of museum
      specimens.
AB  - Museum specimens have provided the material for a large proportion of ancient DNA
      studies conducted during the last 20 years. However, a major drawback of the
      genetic analyses is that the specimens investigated are usually damaged, as parts
      of skin, bone, or a tooth have to be removed for DNA extraction. To get around
      these limitations, we have developed a nondestructive extraction method for bone,
      tooth, and skin samples. We found that it is possible to amplify mitochondrial
      DNA (mtDNA) sequences up to at least 414 bp long from samples up to 164 years
      old. Using this method, almost 90% (35 of 40) of the investigated samples yielded
      amplifiable mtDNA. Moreover, we found that repeated extractions of the same
      samples allowed amplifications of the expected length for all samples at least
      three times and for some samples up to at least five times. Thus this method
      opens up the possibility to repeatedly use museum collections for mtDNA analyses
      without damaging the specimens and thus without reducing the value of
      irreplaceable collections for morphological analyses.

PMID- 15152602
TI  - Isolation of high-quality RNA from gymnosperm and angiosperm trees.
AB  - An improved protocol was developed for efficient and reliable extraction of high
      quality total RNA and mRNA from various tissues of spruce (Picea spp.) and poplar
      (Populus spp.) trees, as well as other plant species. This method was
      specifically optimized for tissues with high content of polysaccharides,
      oleoresin terpenoids, and phenolic secondary metabolites, which often co
      precipitate with RNA and inhibit subsequent reverse transcription. The improved
      protocol yielded up to 600 micrograms of total RNA per gram of tissue suitable
      for standard expressed sequence tags (ESTs), full-length cDNA library
      construction, and for microarray applications.

PMID- 15152603
TI  - One-week 96-well soft agar growth assay for cancer target validation.
AB  - Soft agar growth, used to measure cell anchorage-independent proliferation
      potential, is one of the most important and most commonly used assays to detect
      cell transformation. However, the traditional soft agar assay is time-consuming,
      labor-intensive, and plagued with inconsistencies due to individual subjectivity.
      It does not, therefore, meet the increasing demands of today's oncology drug
      target screening or validation processes. This report describes an alternative 96
      well soft agar growth assay that can function as a replacement for the
      traditional method and overcomes the aforementioned limitations. It offers the
      following advantages: a shortened assay duration (1 week instead of 4 weeks) that
      makes transient transfection or treatment possible; plate reader quantification
      of soft agar growth (measuring cloning efficiency and colony size); and a
      significant reduction in required labor. Higher throughput also makes it possible
      to process large numbers of samples and treatments simultaneously and in a much
      more efficient manner, while saving precious workspace and overall cost.

PMID- 15152604
TI  - SNP allele frequency estimation in DNA pools and variance components analysis.
AB  - The estimation of single nucleotide polymorphism (SNP) allele frequency in pooled
      DNA samples has been proposed as a cost-effective approach to whole genome
      association studies. However, the key issue is the allele frequency window in
      which a genotyping method operates and provides a statistically reliable answer.
      We assessed the homogeneous mass extend assay and estimated the variance
      associated with each experimental stage. We report that a relationship between
      estimated allele frequency and variance might exist, suggesting that high
      statistical power can be retained at low, as well as high, allele frequencies.
      Assuming this relationship, the formation of subpools consisting of 100 samples
      retains an effective sample size greater than 70% of the true sample size, with a
      savings of 11-fold the cost of an individual genotyping study, regardless of
      allele frequency.

PMID- 15152605
TI  - Methylation assay by nucleotide incorporation: a quantitative assay for regional
      CpG methylation density.
AB  - Although the aberrant methylation in CpG islands is of great interest as a
      causative role in human malignancies, it has been very difficult to accurately
      determine methylation density. Here we report a novel microplate-based
      quantitative methylation assay, designated MANIC, for a region containing a
      number of CpG sites based on incorporation of hapten-labeled dCTP at cytosine
      sites where the methylated cytosines have not been converted to uracil by the
      bisulfite treatment. Validation using control DNAs revealed that the method was
      sensitive enough to detect < 1.25% methylated DNA and that calibration curve was
      linear. With this approach, we determined relative methylation density of O6
      methylguanine-DNA methyltransferase gene promoter containing 12 CpG sites among
      the 12 colorectal cancers and corresponding normal mucosal tissues. Consequently,
      MANIC showed a high concordance with results by a quantitative method, bisulfite
      PCR single-stranded conformational polymorphism (BiPS). MANIC is a technique that
      avoids cumbersome procedures such as electrophoresis or the use of radiolabeling
      and is applicable to any sequence regardless of the total number of CpG sites or
      heterogeneity in methylation status.

PMID- 15152606
TI  - Oligo(dA-dT)-dependent signal amplification for the detection of proteins in
      cells.
AB  - An ultrasensitive protein detection system in situ named the ImmunoAT-tailing
      method was developed. It consists of three elementary processes: (i) detection of
      a protein by a primary antibody and a biotinylated secondary antibody; (ii)
      linking of biotinylated 15-base oligo(dA-dT) to the biotinylated immunocomplex
      via streptavidin; and (iii) self-priming elongation of oligo(dA-dT) by the Klenow
      fragment, 3' to 5' exo-. After the elongation reaction in the presence of dATP,
      dTTP, and dye-labeled dUTP, the protein was labeled with a large number of the
      dye molecules. The poly(dA-dT) elongated without the labeled nucleotides was
      detected by 4',6-diamidino-2-phenylindole (DAPI) staining. By combining the
      different labelings, double staining was possible. This ImmunoAT-tailing method
      has a specificity and sensitivity higher than that of tyramide signal
      amplification.

PMID- 15152607
TI  - Linker peptide and affinity tag for detection and purification of single-chain Fv
      fragments.
AB  - The peptide tag GATPQDLNTML, corresponding to amino acids 46-56 of the human
      immunodeficiency virus type 1 (HIV-1) capsid protein p24, is the linear epitope
      of the murine monoclonal antibody CB4-1. This antibody shows high affinity (KD =
      1.8 x 10(-8) M) to the free epitope peptide in solution. The original p24 peptide
      tag and mutant derivatives were fused to the C terminus of a single-chain
      antibody (scFv) and characterized with respect to sensitivity in Western blot
      analyses and behavior in purification procedures using affinity chromatography.
      The p24 tag also proved to be a suitable alternative to the (Gly4Ser)3 linker
      commonly used to connect single-chain antibody variable regions derived from a
      heavy (VH) and light chain (VL). Binding of CB4-1 antibody to the p24 tag was not
      hampered when the tag was located internally in the protein sequence, and the
      specific antigen affinity of the scFv was only slightly reduced. All scFv
      variants were solubly expressed in Escherichia coli and could be purified from
      the periplasm. Our results highlight the p24 tag as a useful tool for purifying
      and detecting recombinantly expressed scFvs.

PMID- 15152608
TI  - Quantitative beta-galactosidase assay suitable for high-throughput applications
      in the yeast two-hybrid system.
AB  - Measurement of beta-galactosidase (beta-gal) activity is an important step in
      every yeast two-hybrid assay, yet many commonly used methods have distinct
      disadvantages, such as being only qualitative, time-consuming, and cumbersome
      when processing large numbers of samples. To overcome these drawbacks, we have
      implemented a novel technique, termed pellet X-gal assay, that allows
      simultaneous quantitative measurements from large numbers of samples with a
      minimum of hands-on time. The method was tested using five different, previously
      described protein-protein interactions and compared to two standard methods, the
      colony filter lift and the liquid ONPG assay. Our assay allows accurate
      quantitative measurements of protein-protein interactions and covers a greater
      dynamic range than the classic ONPG assay. The novel assay is robust and requires
      very little handling, making it suitable for applications in which several
      hundreds of individual protein interaction pairs need to be measured
      simultaneously.

PMID- 15152609
TI  - Evaluation of the CFP-substrate-YFP system for protease studies: advantages and
      limitations.
AB  - A protease can be defined as an enzyme capable of hydrolyzing peptide bonds.
      Thus, characterization of a protease involves identification of target peptide
      sequences, measurement of activities toward these sequences, and determination of
      kinetic parameters. Biological protease substrates based on fluorescent protein
      pairs, which allow for use of fluorescence resonance energy transfer (FRET), have
      been recently developed for in vivo protease activity detection and represent a
      very interesting alternative to chemical substrates for in vitro protease
      characterization. Here, we analyze a FRET system consisting of cyan and yellow
      fluorescent proteins (CFP and YFP, respectively), which are fused by a peptide
      linker serving as protease substrate. Conditions for CFP-YFP fusion protein
      production in Escherichia coli and purification of proteins were optimized. FRET
      between CFP and YFP was found to be optimum at a pH between 5.5 and 10.0, at low
      concentrations of salt and a temperature superior to 25 degrees C. For efficient
      FRET to occur, the peptide linker between CFP and YFP can measure up to 25 amino
      acids. The CFP-substrate-YFP system demonstrated a high degree of resistance to
      nonspecific proteolysis, making it suitable for enzyme kinetic analysis. As with
      chemical substrates, substrate specificity of CFP-substrate-YFP proteins was
      tested towards different proteases and kcat/Km values were calculated.

PMID- 15152610
TI  - The effects of estrogens on learning in rats with chronic brain cholinergic
      deficiency in a Morris water test. Identification of the "passive swimming"
      component.
AB  - Chronic decreases in brain cholinergic functions due to intraventricular
      administration of the neurotoxin AF64A were accompanied by increases in the
      latent period of locating an invisible platform during training of rats in a
      Morris water test, as compared with control sham-operated animals. Recordings of
      the animals' movement trajectories using a video camera along with an original
      computer program (Behavioral Vision) showed that administration of 17beta
      estradiol and its synthetic analog J-861 (0.2 mg/kg p.o. daily for seven days
      before and 10 days after single intraventricular injections of AF64A) improved
      learning. The directivity of platform search trajectories was assessed
      quantitatively using a new parameter--trajectory straightness. Introduction of
      the "passive swimming" parameter allowed periods of immobility in water to be
      identified within the total latent period in animals after administration of
      AF64A; 17beta-estradiol but not J-861 "eliminated" these periods. The new
      parameters (especially trajectory straightness) allowed the ability to learn to
      be discriminated from decreases in mobility, including mobility losses due to
      study agents, in the Morris water test.

PMID- 15152611
TI  - Ernst L. Freud (1892-1970), architect in Berlin and London.

PMID- 15152612
TI  - Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum
      protein glycomics.
AB  - We applied our 'clinical glycomics' technology, based on DNA sequencer/fragment
      analyzers, to generate profiles of serum protein N-glycans of liver disease
      patients. This technology yielded a biomarker that distinguished compensated
      cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity
      and 86% specificity (100% sensitivity and specificity for decompensated
      cirrhosis). In combination with the clinical chemistry-based Fibrotest biomarker,
      compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The
      current 'gold standard' for liver cirrhosis detection is an invasive, costly,
      often painful liver biopsy. Consequently, the highly specific set of biomarkers
      presented could obviate biopsy in many cirrhosis patients. This biomarker
      combination could eventually be used in follow-up examinations of chronic liver
      disease patients, to yield a warning that cirrhosis has developed and that the
      risk of complications (such as hepatocellular carcinoma) has increased
      considerably. Our clinical glycomics technique can easily be implemented in
      existing molecular diagnostics laboratories.

PMID- 15152613
TI  - [Malignant lymphoma competence network].
AB  - The competence network Malignant Lymphomas is one out of 3 oncological networks
      which have been funded by the German Federal Ministry of Education and Research
      since 1999. The network's activities are based on the work of the German lymphoma
      research groups, which have led to significant progress in the diagnosis and
      therapy of malignant lymphoma over the last few years. Based on this
      infrastructure, the network aims to establish a professional quality management
      for the diagnostics and treatment of malignant lymphomas. Key aspects of activity
      include: 1st the establishment of an IT-based information and communication
      platform, 2nd IT-based networking of study groups and collaborating centres of
      pathology and radiotherapy, 3rd epidemiological and health care-economical
      research, 4th research on improved and new therapeutical approaches, 5th evidence
      based medicine. Further information is presented in http://www.lymphome.de.

PMID- 15152614
TI  - [A 66-year old female patient with tachycardia and syncope].
AB  - A 66-year old female patient suffered from paroxysmal tachycardias, palpitations,
      dizziness and once a short period of unconsciousness. The surface ECG showed
      preexcitation, and the clinical diagnosis of WPW syndrome was established. The
      electrophysiological study revealed the rare occurrence of an epicardial
      posteroseptal accessory pathway. Retrograde venous angiography of the coronary
      sinus showed a coronary sinus diverticulum. Ablation of the accessory pathway in
      the neck of the coronary sinus diverticulum was successful. Epicardial accessory
      pathways in a coronary sinus diverticulum are rare. However, successful ablation
      of accessory pathways at this site is safely possible.

PMID- 15152615
TI  - [Early treatment of a Bence-Jones-kappa-light-chain-paraproteinemia].

PMID- 15152616
TI  - [Heart insufficiency: therapy with selective aldosterone antagonists. EPHESUS
      study].

PMID- 15152618
TI  - Response to Cowan: The upper temperature for life -  where do we draw the line?

PMID- 15152617
TI  - Calciphylaxis and vascular calcification: a continuum of extra-skeletal
      osteogenesis.

PMID- 15152620
TI  - Lobar pneumonia.

PMID- 15152619
TI  - Basic biology and clinical impact of immunosenescence.

PMID- 15152621
TI  - Reply: LH/HCG as a monthly injectable contraceptive.

PMID- 15152623
TI  - 2003 Index issue. Cumulative indexes for Volumes 300-312.

PMID- 15152624
TI  - [85th German Radiology Congress. 19-22 May 2004, Wiesbaden, Germany. Abstracts].

PMID- 15152622
TI  - Reply to Spitzer's (2003) reply.

PMID- 15152625
TI  - Abstracts of the American Association of Clinical Endocrinologists 13th Annual
      Meeting and Clinical Congress. April 28-May 2, 2004, Boston, Massachusetts, USA.

PMID- 15152626
TI  - New horizons in chemical space.

PMID- 15152627
TI  - Expanded EU presents promise and challenges.

PMID- 15152628
TI  - FDA publishes analysis of the pipeline problem.

PMID- 15152629
TI  - Patentability in the United States.

PMID- 15152630
TI  - Allen D. Rose.

PMID- 15152631
TI  - Monoclonal antibodies market.

PMID- 15152632
TI  - Atomoxetine hydrochloride.

PMID- 15152633
TI  - FDA head wanted, wimps need not apply.

PMID- 15152634
TI  - Intestinal malrotation with midgut volvulus in a 10-year-old girl.

PMID- 15152635
TI  - Abstracts of the 2nd Eastern Mediterranean Meeting on Cerebral Palsy and
      Developmental Medicine. 13-16 May 2004, Santorini, Greece.

PMID- 15152637
TI  - Abstracts of the Biennial Scientific Meeting of the International Association for
      the Study of the Liver. March 16-20, 2004, Salvador, Bahia, Brazil.

PMID- 15152636
TI  - Abstracts of the 31st European Symposium on Calcified Tissues. Nice, France, 5-9
      June 2004.

PMID- 15152638
TI  - Abstracts of the American Society of Hypertension 19th Annual Meeting. May 18-22,
      2004. New York, New York, USA.

PMID- 15152639
TI  - Standardised coding of diet records: experiences from INTERMAP UK.
AB  - Coding diet records is a basic element of most dietary surveys, yet it often
      receives little attention even though errors in coding can lead to flawed study
      results. In the INTERnational study of MAcro- and micronutrients and blood
      Pressure (INTERMAP study), efforts were made to minimise errors in coding the 18,
      720 diet records. Staff were centrally trained and certified before being able to
      process study data and ongoing quality control checks were performed. This
      involved the senior (site) nutritionist re-coding randomly selected diet records.
      To facilitate standardisation of coding in the UK, a code book was designed; it
      included information about coding brand items, density and portion size
      information, and default codes to be assigned when limited information was
      available for food items. It was found that trainees, despite previous experience
      in coding elsewhere, made coding errors that resulted in errors in estimates of
      daily energy and nutrient intakes. As training proceeded, the number of errors
      decreased. Compilation of the code book was labour-intensive, as information from
      food manufacturers and retailers had to be collected. Strategies are required to
      avoid repetition of this effort by other research groups. While the methods used
      in INTERMAP to reduce coding errors were time consuming, the experiences suggest
      that such errors are important and that they can be reduced.

PMID- 15152640
TI  - Abstracts of the 11th World Congress of Gynecological Endocrinology. Florence,
      Italy, February 26-29, 2004.

PMID- 15152641
TI  - [Abstracts of the 110th Congress of the French Society of Ophthalmology. 8-12 May
      2004, Paris, France].

PMID- 15152642
TI  - HIV counseling, testing, and referral.

PMID- 15152643
TI  - Health professionals to promote a new code of conduct on tobacco control.

PMID- 15152644
TI  - Meaning constructs as predictors of bereavement adjustment: a report from the
      Scott & White Grief Study.
AB  - Nine unique meaning constructs were derived from a content analysis of free
      essays written by 85 mourners in response to the question, "What does the death
      of your loved one mean to you?" These constructs were then treated as predictor
      variables in a quantitative analysis of several indices of bereavement adjustment
      including (a) risk factors of grief pathogenesis and psychometric measures of
      negative grief affect and (b) indicators and correlates of personal growth.
      Mourners who expressed one or more constructs connoting positive themes of hope
      and recovery in their narrative essays fared better on several indicators of
      bereavement adjustment than those expressing solely themes of pain and suffering.
      As a single meaning category, Focusing on Negativity carried the strongest
      statistical relation to outcome measures and correlated with poorer adjustment.
      Implications for combining qualitative and quantitative data are discussed
      together with potential applications to clinical practice.

PMID- 15152645
TI  - Many countries not on target to reach health-related millennium development
      goals.

PMID- 15152646
TI  - Urgent work needed to rebuild health care systems.

PMID- 15152647
TI  - Elective inactivation of total artificial heart technology in non-futile
      situations: inpatients, outpatients and research participants.
AB  - Total artificial heart technology as a potential clinical therapy raises the
      issue of elective device inactivation in both futile and non-futile situations.
      This article explores elective device inactivation in non-futile situations. In
      reply to such requests for inactivation, the medical team should reflect on the
      individual's decision-making capacity, the clinical appropriateness of the
      therapy, and the setting of the request (clinical research vs. clinical
      practice). A decision-making flowchart is presented as a guide for managing
      inactivation requests. In the research setting, current U.S. federal regulations
      are murky as to the matter of study withdrawal made by participants who lack
      decision-making capacity. This compared with clear legal and ethical approaches
      in the non-research setting (clinical practice).

PMID- 15152648
TI  - Endothelial dilatory function predicts individual susceptibility to renal damage
      in the 5/6 nephrectomized rat.

PMID- 15152649
TI  - The Arabic Scale of Death Anxiety (ASDA): its development, validation, and
      results in three Arab countries.
AB  - The Arabic Scale of Death Anxiety (ASDA) was constructed and validated in a
      sample of undergraduates (17-33 yrs) in 3 Arab countries, Egypt (n = 418), Kuwait
      (n = 509), and Syria (n = 709). In its final form, the ASDA consists of 20
      statements. Each item is answered on a 5-point intensity scale anchored by 1: No,
      and 5: Very much. Alpha reliabilities ranged from .88 to .93, and item-remainder
      correlations ranged between .27 and .74; the 1-week test-retest reliability was
      .90 (Egyptians only), denoting high internal consistency and stability. The
      correlations between the ASDA and Templer's DAS ranged from .60 to .74 denoting
      high convergent validity of the ASDA against the DAS in the 3 Arab countries.
      Four factors were extracted in the Egyptian sample and labeled "Fear of dead
      people and tombs", "Fear of postmortem events", "Fear of lethal disease", and
      "death preoccupation". The first two factors were almost completely identical in
      the three countries. The item, "I fear the torture of the grave", had a very high
      mean score. There were significant correlations between the ASDA and death
      depression, death obsession, reasons for death fear, and general anxiety,
      depression, obsession-compulsion, neuroticism, and being a female. All female
      groups attained significantly higher mean ASDA scores than their male
      counterparts. Kuwaitis had higher mean ASDA total scores, in comparison with
      their Egyptian and Syrian counterparts, whereas female Syrians attained the
      lowest mean ASDA total score in proportion to their female peers.

PMID- 15152650
TI  - Prognostic value of ambulatory blood pressure recordings in patients with treated
      hypertension.

PMID- 15152652
TI  - [Linkage analysis in Japanese patients with schizophrenia].

PMID- 15152651
TI  - Can a television series change attitudes about death? A study of college students
      and Six Feet Under.
AB  - This study examined the effects of viewing 10 episodes of the television series
      Six Feet Under to assess whether such programming could influence college
      students' attitudes about death and dying. Students were administered the Death
      Attitude Profile--Revised, the Multidimensional Fear of Death Scale, and the
      short version of the Threat Index, prior to and after viewing. Significant
      changes were found on a number of measures. These results are similar to the
      effects of didactic death education courses.

PMID- 15152653
TI  - [Possible involvement of DNA methylation in pathogenesis of mental disorders-
      special reference to the twin study].

PMID- 15152654
TI  - [Study on genes involved in pathogenesis of schizophrenia with DNA microarray].

PMID- 15152655
TI  - [Gene expression in mental diseases--from DNA to RNA].

PMID- 15152656
TI  - [Role of psychiatrists in long-term care for the aged].

PMID- 15152657
TI  - [Role of psychiatrists in early diagnosis of senile dementia].

PMID- 15152658
TI  - [Drug therapy for aged patients with Alzheimer disease].

PMID- 15152659
TI  - Levoglucosan in PM2.5 at the Fresno supersite.
AB  - Ambient air monitoring for PM2.5 has been conducted on a daily basis at the
      Fresno, CA, supersite since 1999. It has been found that PM2.5 concentrations
      routinely exceed the National Ambient Air Quality Standards during the winter
      months. In an effort to determine the effect of biomass burning on PM2.5
      concentrations, samples during 2000 were analyzed for levoglucosan, palmitic
      acid, and stearic acid. The results of this study are presented.

PMID- 15152660
TI  - Modeling the benefits of power plant emission controls in Massachusetts.
AB  - Older fossil-fueled power plants provide a significant portion of emissions of
      criteria air pollutants in the United States, in part because these facilities
      are not required to meet the same emission standards as new sources under the
      Clean Air Act. Pending regulations for older power plants need information about
      any potential public health benefits of emission reductions, which can be
      estimated by combining emissions information, dispersion modeling, and
      epidemiologic evidence. In this article, we develop an analytical modeling
      framework that can evaluate health benefits of emission controls, and we apply
      our model to two power plants in Massachusetts. Using the CALPUFF atmospheric
      dispersion model, we estimate that use of Best Available Control Technology
      (BACT) for NOx and SO2 would lead to maximum annual average secondary particulate
      matter (PM) concentration reductions of 0.2 microg/m3. When we combine
      concentration reductions with current health evidence, our central estimate is
      that the secondary PM reductions from these two power plants would avert 70
      deaths per year in a population of 33 million individuals. Although benefit
      estimates could differ substantially with different interpretations of the health
      literature, parametric perturbations within CALPUFF and other simple model
      changes have relatively small impacts from an aggregate risk perspective. While
      further analysis would be required to reduce uncertainties and expand on our
      analytical model, our framework can help decision-makers evaluate the magnitude
      and distribution of benefits under different control scenarios.

PMID- 15152662
TI  - Aerosol laser ablation mass spectrometry of suspended powders from PM sources and
      its implications to receptor modeling.
AB  - Primary sources of particulate matter (PM) were analyzed by suspending powdered
      samples into an aerosol laser ablation mass spectrometer (LAMS). PM sources
      studied included vehicle exhaust particulates, dust from a non-ferrous smelter,
      cement powder, incinerator fly ash, two coal fly ash samples, and two soils.
      Marker peaks signified certain PM source sectors: construction particles could be
      distinguished by abundant Ca and Ca compounds, fuel combustion was marked by
      elemental carbon clusters, and nonferrous industrial particles showed inorganic
      As, Cu, Pb, Zn, and SOx. In addition to the distinction between particles from
      these different source sectors, mass spectral results also showed that for a
      single source, different particle types existed, and among different sources
      within a sector, similar spectra were present. The aerosol LAMS results show the
      difficulty in differentiating among separate fly ash sources as well as among
      different soil samples. A particle class balance receptor model that measures the
      amount of specific particle types rather than the amount of a chemical component
      is suggested as a means of source apportionment when particle spectra with
      overlapping source possibilities occur. The assumptions and limitations of
      receptor modeling aerosol LAMS data are also described. In particular, methods
      need to be developed to account for the contribution of secondary sources.

PMID- 15152661
TI  - Large-volume injection PTV-GC-MS analysis of polycyclic aromatic hydrocarbons in
      air and sediment samples.
AB  - For the analysis of trace organic pollutants in environmental samples using a gas
      chromatographic (GC) instrument, large-volume injection using the programmable
      temperature vaporization (PTV) technique has many advantages over the traditional
      split/splitless injection. By increasing the injection volume from 1 or 2 microL
      with a split/splitless inlet to 60 microL or higher with the PTV inlet,
      analytical sensitivity is greatly enhanced for analytes with low concentrations.
      Results obtained from optimization of instrument operational parameters for
      analyzing polycyclic aromatic hydrocarbons (PAHs) are reported in this paper. The
      laboratory method detection limits for 16 PAHs and six deuterated PAH surrogates
      were determined using seven replicate spike samples. The initial temperature of
      the inlet was found to be critical in determining the analytical sensitivity of
      PAHs with two or three rings due to loss of these relatively highly volatile
      compounds during solvent vaporization. For most PAHs, the response of the mass
      spectrometry detector increased proportionally as the total injected volume was
      increased up to 150 microL. Significant interference from rubber material of the
      sample vial septa was observed.

PMID- 15152663
TI  - Real-time indoor and outdoor measurements of black carbon in an occupied house:
      an examination of sources.
AB  - Black carbon (BC) was measured every 5 min for two years (May 1998-May 2000)
      inside and immediately outside a northern Virginia house (suburban Washington,
      DC) occupied by two nonsmokers. Two aethalometers, which measure BC by optical
      transmission through a quartz fiber tape, were employed indoors and outdoors.
      Meteorological parameters were obtained on an hourly basis from nearby Dulles
      airport. Indoor activities were recorded to identify indoor sources such as
      combustion activities, which occurred 9% of the time during the first year and 4%
      of the time during the second year. At times without indoor sources,
      indoor/outdoor BC ratios averaged 0.53 in the first year and 0.35 in the second
      year. The main outdoor source of BC was the general regional background,
      contributing 83-84% of the total during each of the two years. Morning rush hour
      traffic contributed 8-9% of the total BC. An evening peak in the fall and winter,
      thought to include contributions from wood burning, was responsible for
      approximately 8% of the annual average BC concentration. The main indoor sources
      of BC were cooking and candle burning, contributing 16 and 31%, respectively, of
      the annual average indoor concentrations in the two years. Relative humidity (RH)
      affected the outdoor aethalometer in both years. An artifact associated with the
      tape advance was noted for the aethalometer, but a correction factor was
      developed that reduced the associated error by a factor of 2.

PMID- 15152664
TI  - Measurements of personal exposure to nitrogen dioxide in four Mexican cities in
      1996.
AB  - Nitrogen dioxide is a ubiquitous pollutant in urban areas. Indoor NO2
      concentrations are influenced by penetration of outdoor concentrations and by
      indoor sources. The objectives of this study were to evaluate personal exposure
      to NO2, taking into account human time-activity patterns in four Mexican cities.
      Passive filter badges were used for indoor, outdoor, and personal NO2
      measurements over 48 hr and indoor workplace measurements over 16 hr. Volunteers
      completed a questionnaire on exposure factors and a time-activity diary during
      the sample period. An unpaired t test, an analysis of variance (ANOVA), and a
      linear regression were performed to compare differences among cities and mean
      personal NO2 concentrations involving housing characteristics, as well as to
      determine which variables predicted the personal NO2 concentration. Sampling
      periods were in April, May, and June 1996 in Mexico City, Guadalajara,
      Cuernavaca, and Monterrey. All 122 volunteers in the study were working adults,
      with a mean age of 34 (SD +/- 7.38); 64% were female, and the majority worked in
      public offices and universities. The highest NO2 concentrations were found in
      Mexico City (36 ppb for outdoor, 57 ppb for indoor, and 39 ppb for personal
      concentration) and the lowest in Monterrey (19 ppb for outdoor, 24 ppb for
      indoor, and 24 ppb for personal concentration). Significant differences in NO2
      concentrations were found among the cities in different microenvironments. During
      the sampling period, volunteers spent 85% of their time indoors. The highest
      personal NO2 concentration was found when volunteers kept their windows closed (p
      = 0.03). In the regression model adjusted by city and gender, the best predictors
      of personal NO2 concentration were outdoor levels and time spent outdoors (R2 =
      0.68). These findings suggest that outdoor NO2 concentrations were an important
      influence on the personal exposure to NO2, due to the specific characteristics
      and personal behavior of the people in these Mexican cities.

PMID- 15152665
TI  - Slurry-phase ozonation for remediation of sediments contaminated by polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of toxic, persistent,
      bioaccumulating organic compounds containing two or more fused aromatic rings.
      They are listed by the U.S. Environmental Protection Agency as priority
      pollutants because of their carcinogenicity and toxicity. Employing ozonation as
      a remediation technique, this work investigated the treatability of a sediment
      sample from a freshwater boat slip subjected to coal tar contamination over a
      long period. The contaminated sediment sample contained high levels of PAHs in
      the forms of naphthalene, phenanthrene, pyrene, and benzo[a]pyrene, among other
      byproducts present in the humic and solid phases of the sediment. The objectives
      of this work were to examine (1) the degradation of PAHs in the contaminated
      sediment as treated by ozonation in the slurry form, (2) the effects of ozonation
      upon the soil matrix and the biodegradability of the resultant PAH intermediates,
      and (3) the feasibility of a combined technique using O3 as a pretreatment
      followed by biological degradation. The sediment was made into 3% w/w soil
      slurries and ozonated in a 1.7-L semi-batch, well-stirred reactor equipped with
      pH control and a cold trap for the gaseous effluent. Samples were collected after
      different ozonation durations and tested for biochemical oxygen demand (BOD),
      chemical oxygen demand (COD), UV absorbance, and toxicity, along with
      quantitative and qualitative determinations of the parent and daughter
      intermediates using gas chromatography/flame ionization detection (GC/FID),
      GC/mass spectrometry (MS), and ion chromatography (IC) techniques. The GC/MS
      technique identified 16 compounds associated with the humic and solid phases of
      the sediment. Intermediates identified at different ozonation times suggested
      that the degradation of PAHs was initiated by an O3 attack resulting in ring
      cleavage, followed by the intermediates' oxidation reactions with O3 and the
      concomitant OH radical toward their mineralization. Results suggested that
      ozonation for 2 hr removed 50-100% of various PAHs in the solid and liquid phases
      (as well as the aqueous and gaseous media resulting from the treatment process)
      of the sediment sample and that organic and inorganic constituents of the
      sediment were also altered by ozonation. Measurements and comparisons of BOD,
      COD, UV absorbance, and toxicity of the samples further suggested that ozonation
      improved the bioavailability and biodegradability of the contaminants, despite
      the increased toxicity of the treatment effluent. An integrated chemical
      biological system appeared to be feasible for treating recalcitrant compounds.

PMID- 15152667
TI  - Use of treated bark for the removal of lipids from water.
AB  - Raw, biologically treated bark and bark impregnated with transition metal ions
      were used to retain the lipids from synthetic emulsions. Several experimental
      parameters affecting the lipid removal efficiency (RE) were studied (initial
      concentration of lipids, temperature, time, pH, carboxylic acid chain length,
      etc.). Saturated bark was characterized using Fourier transform infrared (FTIR)
      spectroscopy and light microscopy, and the treated bark wetting index was
      determined. Results show that lipid removal can exceed 95% of the initial
      concentration at a pH lower than 7. The uptake of lipids by these sorbents varied
      from 0.2 to 2.5 g/g of dry bark. Trials for regenerating the sorbent saturated by
      lipids allowed the recovery of approximately 95% of lipids. The calorific value
      of the saturated bark was approximately 79% that of domestic fuel and can be
      considered as an energy source, thus avoiding its waste disposal. These results
      may upgrade the treatment of wastewater generated by several industrial sectors,
      such as the food industry, surface treatment, and so on.

PMID- 15152668
TI  - Factors affecting heavy-duty diesel vehicle emissions.
AB  - Societal and governmental pressures to reduce diesel exhaust emissions are
      reflected in the existing and projected future heavy-duty certification standards
      of these emissions. Various factors affect the amount of emissions produced by a
      heterogeneous charge diesel engine in any given situation, but these are poorly
      quantified in the existing literature. The parameters that most heavily affect
      the emissions from compression ignition engine-powered vehicles include vehicle
      class and weight, driving cycle, vehicle vocation, fuel type, engine exhaust
      aftertreatment, vehicle age, and the terrain traveled. In addition, engine
      control effects (such as injection timing strategies) on measured emissions can
      be significant. Knowing the effect of each aspect of engine and vehicle operation
      on the emissions from diesel engines is useful in determining methods for
      reducing these emissions and in assessing the need for improvement in inventory
      models. The effects of each of these aspects have been quantified in this paper
      to provide an estimate of the impact each one has on the emissions of diesel
      engines.

PMID- 15152666
TI  - Levels and characteristic homologue patterns of polychlorinated dibenzo-p-dioxins
      and dibenzofurans in various incinerator emissions and in air collected near an
      incinerator.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were monitored in
      stack gas and fly ash of various Korean incinerators and in air samples collected
      near the facilities. Concentrations of PCDD/Fs in emissions were investigated,
      and characteristic PCDD/F homologue patterns were classified using statistical
      analyses. The PCDD/F emission levels in stack gas and fly ash samples from small
      incinerators (SIs) were higher than those from municipal solid waste incinerators
      (MSWIs). The PCDD/F concentrations ranged between 0.38 and 1.16 pg I-TEQ/m3 (21.2
      75.2 pg/m3) in ambient air samples. The lower-chlorinated furans were the
      dominant components in most of the stack gas and fly ash samples from SIs,
      although this was not the case for fly ash from MSWIs. This homologue pattern is
      consistent with other studies reporting a high fraction of lower-chlorinated
      furans in most environmental samples affected by incinerator emissions, and it
      can be used as an indicator to assess the impact of such facilities on the
      surrounding environment.

PMID- 15152669
TI  - Evolution and kinetics of volatile organic compounds generated during low
      temperature polymer degradation.
AB  - A method using direct flame ionization detector (FID) measurement was developed
      to study total volatile organic compound (VOC) emissions during thermal
      degradation of polymers. This method was used to estimate organic emissions from
      different polymers, such as low-density polyethylene (PE), polypropylene (PP),
      polyethylene terephthalate (PET), and commingled postconsumer streams, such as
      recycled carpet residue and auto shredder residue (ASR). The effects of process
      parameters, such as temperature, heating rate, and residence time, were also
      studied. Significant VOC emissions were observed at normal processing
      temperatures, particularly from recycled polymers. Each polymer showed a distinct
      evolution pattern during its thermal degradation. The kinetics of VOC emissions
      were also studied using a nonisothermal technique. The kinetic parameters were in
      agreement with data from the literature.

PMID- 15152670
TI  - Using continuous PM2.5 monitoring data to report an air quality index.
AB  - As stated in 40 CFR 58, Appendix G (2000), statistical linear regression models
      can be applied to relate PM2.5 continuous monitoring (CM) measurements with
      federal reference method (FRM) measurements, collocated or otherwise, for the
      purpose of reporting the air quality index (AQI). The CM measurements can then be
      transformed via the model to remove any bias relative to FRM measurements. The
      resulting FRM-like modeled measurements may be used to provide more timely
      reporting of a metropolitan statistical area's (MSA's) AQI. Of considerable
      importance is the quality of the model used to relate the CM and FRM
      measurements. The use of a poor model could result in misleading AQI reporting in
      the form of incorrectly claiming either good or bad air quality. This paper
      describes a measure of adequacy for deciding whether a statistical linear
      regression model that relates FRM and continuous PM2.5 measurements is sufficient
      for use in AQI reporting. The approach is the U.S. Environmental Protection
      Agency's (EPA's) data quality objectives (DQO) process, a seven-step strategic
      planning approach to determine the most appropriate data type, quality, quantity,
      and synthesis for a given activity. The chosen measure of model adequacy is r2,
      the square of the correlation coefficient between FRM measurements and their
      modeled counterparts. The paper concludes by developing regression models that
      meet this desired level of adequacy for the MSAs of Greensboro/Winston-Salem/High
      Point, NC; and Davenport/Moline/Rock Island, IA/IL. In both cases, a log
      transformation of the data appeared most appropriate. For the data from the
      Greensboro/Winston-Salem/High Point MSA, a simple linear regression model of the
      FRM and CM measurements had an r2 of 0.96, based on 227 paired observations. For
      the data from the Davenport/Moline/Rock Island MSA, due to seasonal differences
      between CM and FRM measurements, the simple linear regression model had to be
      expanded to include a temperature dependency, resulting in an r2 of 0.86, based
      on 214 paired observations.

PMID- 15152671
TI  - [Update endocrinology: Thyroid sonography].
AB  - Thyroid ultrasound has developed to be an important diagnostic method. Thyroid
      and extrathyroid diseases can be differentiated. Ultrasonography shows an exact
      image of thyroid structures in which typical images for some pathological
      entities can be observed. Clinical experience with thyroid diseases is essential
      when using thyroid ultrasonography. Thyroid ultrasonography does not correlate
      with histopathologic findings very well. Therefore fine needle aspiration biopsy
      should be used without hesitation. Solitary thyroid nodules larger than 1-1.5 cm
      in diameter or other potentially malignant structures must be investigated by a
      fine needle aspiration biopsy. Cytopathologic results of a fine needle aspiration
      biopsy have a high accuracy, but follicular neoplasms need a histopathologic
      examination to discriminate between an adenoma and a follicular carcinoma. Colour
      flow Doppler ultrasonography gives helpful information about the blood
      circulation but is not necessary for a reliable diagnostic work up of thyroid
      diseases. Clinical findings, laboratory results, ultrasonography and fine needle
      aspiration biopsy can be used alone or in combination, depending on the
      indication observed, to help find the accurate diagnosis.

PMID- 15152672
TI  - [Sonography of head and neck].
AB  - A brief, schematic summary of a workshop held in Davos 2003 is presented.
      Sonography of the head and neck has been carried out successfully since the
      beginning of the sonographical era, as this region is readily accessible to the
      transducer head and the superficial position of the organ can be very well
      visualized. The prerequisites are a high-resolution transducer-head (around 7.5
      MHz), operator experience and good knowledge of the relevant anatomy. The type of
      transducer selected--linear or mechanical wobbler--plays a subordinate role, and
      color Doppler technology is not mandatory. This brief presentation will not
      address the thyroid gland, the cervical vessels, the paranasal sinuses, the
      facial soft tissue or the pharynx.

PMID- 15152673
TI  - [Practical aspects of breast ultrasound].
AB  - Breast ultrasound has become an important part of senological investigation and
      is considered as the most important complementary method to mammography. The
      strengths of ultrasound are the evaluation of the juvenile radiodense breast,
      peripherical breast lesions and the evaluation of mammary cysts. After the
      general examination of the mammary gland and its surroundings, breast lesions are
      evaluated based on the following criteria: shape and border of the tumor,
      structural breaks, tumor protuberances and posterior shadowing or enhancement,
      compressibility and shifting. The sensitivity of breast ultrasound in finding
      breast cancer is around 90%, its specifity 80% are lower in small tumors. That's
      why ultrasound must be combined with clinical findings and other imaging like
      mammogaphy and MRI to find a reliable diagnosis. A histological work up is
      indicated if not all the methods show benign findings.

PMID- 15152674
TI  - [Ultrasound in pregnancy--practical aspects].
AB  - According to the payments agreement of the health insurance law two screening
      scans at 10-13 weeks and 20-23 weeks respectively are part of the low-risk
      pregnancy care. The first-trimestre-scan includes the determination of the
      gestational age, the anatomical integrity of the fetus and the chorionicity in
      case of monochorionic twins. The 20-23 week scan has to evaluate the fetal
      growth, fetal abnormalities and the placental site. Doppler sonography is
      reserved for high risk pregnancies, especially for hypertensive disorders and
      fetal growth retardation, for the evaluation of fetal anemia in case of blood
      group alloimmunisation and for the detection of the twin-twin-transfusion
      syndrome in monochorionic twins.

PMID- 15152676
TI  - [A 57-year-old patient with syncope while swallowing].

PMID- 15152675
TI  - [Thoraxsonography--part 2--Subpleural lung lesions].
AB  - In many cases of pulmonary diseases extending up to the pleura, ultrasound helps
      to identify the etiology of the lesion. There are several sonomorphological
      criteria to differentiate peripheral pulmonary consolidations. The sonomorphology
      of pneumonic lung infiltration reveals typical changes: bronchoaerogram,
      fluidobronchogram, parapneumonic effusion, abscess formation. The extent of
      infiltration is sometimes underestimated due to artefacts. In sonography lung
      cancers are echopoor, rounded and polypoid, show sharp and serrated margins. The
      accuracy of ultrasound-guided transcutane biopsy in carcinomas is higher than
      90%. The rate of pneumothorax is 2.6%, those requiring drainage are about 1%.
      Haemoptyses occur 1-2% of the punctures, most commonly in cases of chronic
      pneumonia. When a pulmonary embolism develops, thoracic sonography in 70-90%
      reveals subpleural sound-permeable lesions: embolism-related alveolar edemas and
      hemorrhages--early reperfusionable infarcts and triangular late infarcts. In
      compression atelectasis there usually is a homogeneous, hyperechoic
      transformation, shaped like a pointed cap or a wedge.

PMID- 15152677
TI  - [Strategies against jet lag].

PMID- 15152678
TI  - ["Through the horny or ivory gate" -- dream interpretation in the Antiquity. 2.
      From Artemidor to Sigmund Freud].

PMID- 15152679
TI  - [Medical literature quiz. A still life. Gustave Flaubert, Education
      sentimentale].

PMID- 15152680
TI  - Photon penetration and scatter in micro-pinhole imaging: a Monte Carlo
      investigation.
AB  - Pinhole SPECT is rapidly gaining popularity for imaging laboratory animals using
      gamma-emitting molecules. Penetration and scattering of gamma radiation in the
      pinhole edge material can account for a significant fraction of the total number
      of photons detected, particularly if the pinholes have small diameters. This
      study characterizes the effects of penetration and scatter with micro-pinholes
      made of lead, tungsten, gold and platinum. Monte Carlo simulations are performed
      for 1-125 (27-35 keV) and Tc-99m (140 keV) point sources with pinhole diameters
      ranging from 50 to 500 microm. The simulations account for the effects of photo
      electric interaction, Rayleigh scattering, Compton scattering, ionization,
      bremsstrahlung and electron multiple scattering. As a typical example, in the
      case of a Tc-99m point source and pinholes with a diameter of 300 microm in gold
      or platinum, approximately 55% of the photons detected resulted from penetration
      and approximately 3% from scatter. For pinhole diameters ranging from 100 to 500
      microm, the penetration fraction for tungsten and lead was approx a factor of 1.0
      to 1.6 higher and the scatter fraction was 1.0 to 1.8 times higher than in case
      of gold or platinum. Using I-125 instead of Tc-99m decreases the penetration
      fraction by a factor ranging from 3 to 11 and the scatter fraction by a factor
      ranging from 12 to 40. For all materials studied, the total amounts of penetrated
      and scattered photons changed approximately linearly with respect to the pinhole
      diameter.

PMID- 15152681
TI  - Optimizing Compton camera geometries.
AB  - Compton cameras promise to improve the characteristics of nuclear medicine
      imaging, wherein mechanical collimation is replaced with electronic collimation.
      This leads to huge gains in sensitivity and, consequently, a reduction in the
      radiation dosage that needs to be administered to the patient. Design
      modifications that improve the sensitivity invariably compromise resolution. The
      scope of the current project was to determine an optimal design and configuration
      of a Compton camera that strikes a balance between these two properties.
      Transport of the photon flux from the source to the detectors was simulated with
      the camera geometry serving as the parameter to be optimized. Two variations of
      the Boltzmann photon transport equation, with and without photon polarization,
      were employed to model the flux. Doppler broadening of the energy spectra was
      also included. The simulation was done in a Monte Carlo framework using GEANT4.
      Two clinically relevant energies, 140 keV and 511 keV, corresponding to 99mTc and
      18F were simulated. The gain in the sensitivity for the Compton camera over the
      conventional camera was 100 fold. Neither Doppler broadening nor polarization had
      any significant effect on the sensitivity of the camera. However, the spatial
      resolution of the camera was affected by these processes. Doppler broadening had
      a deleterious effect on the spatial resolution, but polarization improved the
      resolution when accounted for in the reconstruction algorithm.

PMID- 15152682
TI  - Developing a quality control protocol for diffusion imaging on a clinical MRI
      system.
AB  - This work describes the development of a quality control protocol, which can be
      implemented to assess the accuracy, precision and reproducibility of the apparent
      diffusion coefficient (ADC) measurement on a clinical magnetic resonance imaging
      (MRI) system. The precision and accuracy of the ADC measurement are analysed with
      regard to MRI system noise, signal reproducibility and differences between
      nominal and effective b values. Two aqueous test-solutions of CuSO4 and sucrose
      are prepared for the quality control protocol. ADC measurement with the CuSO4
      solution is more sensitive to differences between nominal and effective b values,
      on account of the solution's high ADC. ADC measurement with the sucrose solution
      is more sensitive to signal reproducibility due to the solution's low baseline
      signal intensity. The ADC of the test-solutions is measured on an MRI system at
      our centre with a sequence used for clinical studies using diffusion imaging. Two
      parameters, Q and R, are defined for the analysis of the quality control ADC
      values. The Q parameter is the ratio of the standard deviation of the quality
      control mean ADC values over time to the optimal standard deviation, as derived
      from the effect of thermal noise on the ADC measurement uncertainty. Analysis
      with the Q parameter indicates that signal reproducibility errors contribute to
      ADC variations on our MRI system when imaging with high b values (b > 500 mm s(
      2)), whereas differences between nominal and effective b values have a greater
      impact on the ADC measurement when imaging with low b values (b < 500 mm s(-2)).
      The R parameter is defined as the ratio of the directional variation of the ADC
      quality control values to the uncertainty of the ADC measurement. Analysis with
      the R parameter shows that the effect of directional variation of the ADC
      measurement on our MRI system is more pronounced when imaging with low b values.
      The quality control protocol identified a systematic error, which introduced a
      small system-induced anisotropy in the ADC measurement. This error is currently
      taken into account in the analysis of clinical studies employing the diffusion
      imaging sequence used in this quality control protocol.

PMID- 15152683
TI  - A novel method for producing x-ray test objects and phantoms.
AB  - A novel method for producing customized x-ray test objects and clinically
      realistic phantoms has been developed. Test objects can be created with a drawing
      software package and the digital images can be printed on a standard inkjet
      printer but using potassium iodide solution in place of the cartridge's ink. The
      reproducibility and the consistency, the limiting spatial resolution, the
      uniformity as well as the potassium iodide thickness per print have been
      evaluated. The relationship between the number of prints, grey levels and the
      radiation contrast was investigated and quantified. A copy of the Leeds TO10
      contrast detail test object was printed and the x-ray images of the Leeds TO10
      and of the printed Leeds TO10 were compared. In addition, the potential use of
      this method was demonstrated by reproducing a percutaneous transluminal coronary
      angioplasty clinical digital image. The reproducibility and consistency of this
      method was found to be better than 0.1%. The limiting spatial resolution of the
      printer using ink was found to be 3.55 1p mm(-1) but it deteriorated when the ink
      was replaced with potassium iodide and as the print density increases. The
      uniformity across the printed area was found to be satisfactory although an
      artefact due to the printer was present in the x-ray images. The comparison
      between the Leeds TO10 and the printed Leeds TO10 gave differences less than 10%.
      A good agreement between the clinical image and the printed clinical image was
      found. In conclusion, the method is a reliable, cost-effective, flexible and
      alternative way for producing x-ray test objects and clinically related phantoms.

PMID- 15152684
TI  - Monte Carlo simulations in CT for the study of the surface air kerma and energy
      imparted to phantoms of varying size and position.
AB  - A Monte Carlo computational model of CT has been developed and used to
      investigate the effect of various physical factors on the surface air kerma
      length product, the peak surface air kerma, the air kerma length product within a
      phantom and the energy imparted. The factors investigated were the bow-tie filter
      and the size, shape and position of a phantom which simulates the patient. The
      calculations show that the surface air kerma length product and the maximum
      surface air kerma are mainly dependent on phantom position and decrease along the
      vertical axis of the CT plane as the phantom surface moves away from the
      isocentre along this axis. As a result, measurements using standard body
      dosimetry phantoms may underestimate the skin dose for real patients. This result
      is specially important for CT fluoroscopic procedures: for an adult patient the
      peak skin dose can be 37% higher than that estimated with a standard measurement
      on the body AAPM (American Association of Physicists in Medicine) phantom. The
      results also show that the energy imparted to a phantom is mainly influenced by
      phantom size and is nearly independent of phantom position (within 3%) and shape
      (up to 5% variation). However, variations of up to 30% were found for the air
      kerma to regions within the AAPM body phantom when it is moved vertically. This
      highlights the importance of calculating doses to organs taking into account
      their size and position within the gantry.

PMID- 15152685
TI  - Experiments with the nonlinear and chaotic behaviour of the multiplicative
      algebraic reconstruction technique (MART) algorithm for computed tomography.
AB  - Among the iterative reconstruction algorithms for tomography, the multiplicative
      algebraic reconstruction technique (MART) has two advantages that make it stand
      out from other algorithms: it confines the image (and therefore the projection
      data) to the convex hull of the patient, and it maximizes entropy. In this paper,
      we have undertaken a series of experiments to determine the importance of MART
      nonlinearity to image quality. Variants of MART were implemented aiming to
      exploit and exaggerate the nonlinear properties of the algorithm. We introduce
      the Power MART, Boxcar Averaging MART and Bouncing MART algorithms. Power MART is
      linked to the relaxation concept. Its behaviour is similar to that of the chaos
      of a logistic equation. There appears to be an antagonism between increasing
      nonlinearity and noise in the projection data. The experiments confirm our
      general observation that regularization as a means of solving simultaneous linear
      equations that are underdetermined is suboptimal: it does not necessarily select
      the correct image from the hyperplane of solutions, and so does not maximize the
      image quality:x-ray dose ratio. Our investigations prove that there is scope to
      optimize CT algorithms and thereby achieve greater dose reduction.

PMID- 15152686
TI  - Radiation-induced cardiomyopathy as a function of radiation beam gating to the
      cardiac cycle.
AB  - Portions of the heart are often unavoidably included in the primary treatment
      volume during thoracic radiotherapy, and radiation-induced heart disease has been
      observed as a treatment-related complication. Such complications have been
      observed in humans following radiation therapy for Hodgkin's disease and
      treatment of the left breast for carcinoma. Recent attempts have been made to
      prevent re-stenosis following angioplasty procedures using external beam
      irradiation. These attempts were not successful, however, due to the large volume
      of heart included in the treatment field and subsequent cardiac morbidity. We
      suggest a mechanism for sparing the heart from radiation damage by synchronizing
      the radiation beam with the cardiac cycle and delivering radiation only when the
      heart is in a relatively hypoxic state. We present data from a rat model testing
      this hypothesis and show that radiation damage to the heart can be altered by
      synchronizing the radiation beam with the cardiac cycle. This technique may be
      useful in reducing radiation damage to the heart secondary to treatment for
      diseases such as Hodgkin's disease and breast cancer.

PMID- 15152687
TI  - A spatio-temporal simulation model of the response of solid tumours to
      radiotherapy in vivo: parametric validation concerning oxygen enhancement ratio
      and cell cycle duration.
AB  - Advanced bio-simulation methods are expected to substantially improve
      radiotherapy treatment planning. To this end a novel spatio-temporal patient
      specific simulation model of the in vivo response of malignant tumours to
      radiotherapy schemes has been recently developed by our group. This paper
      discusses recent improvements to the model: an optimized algorithm leading to
      conformal shrinkage of the tumour as a response to radiotherapy, the introduction
      of the oxygen enhancement ratio (OER), a realistic initial cell phase
      distribution and finally an advanced imaging-based algorithm simulating the
      neovascularization field. A parametric study of the influence of the cell cycle
      duration Tc, OER, OERbeta for the beta LQ parameter on tumour growth. shrinkage
      and response to irradiation under two different fractionation schemes has been
      made. The model has been applied to two glioblastoma multiforme (GBM) cases, one
      with wild type (wt) and another one with mutated (mt) p53 gene. Furthermore, the
      model has been applied to a hypothetical GBM tumour with alpha and beta values
      corresponding to those of generic radiosensitive tumours. According to the model
      predictions, a whole tumour with shorter Tc tends to repopulate faster, as is to
      be expected. Furthermore, a higher OER value for the dormant cells leads to a
      more radioresistant whole tumour. A small variation of the OERbeta value does not
      seem to play a major role in the tumour response. Accelerated fractionation
      proved to be superior to the standard scheme for the whole range of the OER
      values considered. Finally, the tumour with mt p53 was shown to be more
      radioresistant compared to the tumour with wt p53. Although all simulation
      predictions agree at least qualitatively with the clinical experience and
      literature, a long-term clinical adaptation and quantitative validation procedure
      is in progress.

PMID- 15152688
TI  - Geometric leaf placement strategies.
AB  - Geometric leaf placement strategies for multileaf collimators (MLCs) typically
      involve the expansion of the beam's-eye-view contour of a target by a uniform MLC
      margin, followed by movement of the leaves until some point on each leaf end
      touches the expanded contour. Film-based dose-distribution measurements have been
      made to determine appropriate MLC margins--characterized through an index d90-
      for multileaves set using one particular strategy to straight lines lying at
      various angles to the direction of leaf travel. Simple trigonometric
      relationships exist between different geometric leaf placement strategies and are
      used to generalize the results of the film work into d90 values for several
      different strategies. Measured d90 values vary both with angle and leaf placement
      strategy. A model has been derived that explains and describes quite well the
      observed variations of d90 with angle. The d90 angular variations of the
      strategies studied differ substantially, and geometric and dosimetric reasoning
      suggests that the best strategy is the one with the least angular variation.
      Using this criterion, the best straightforwardly implementable strategy studied
      is a 'touch circle' approach for which semicircles are imagined to be inscribed
      within leaf ends, the leaves being moved until the semicircles just touch the
      expanded target outline.

PMID- 15152690
TI  - Delivery time comparison for intensity-modulated radiation therapy with/without
      flattening filter: a planning study.
AB  - The treatment delivery time of intensity-modulated radiation therapy (IMRT) with
      a multileaf collimator (MLC) is generally longer than that of conventional
      radiotherapy. In theory, removing the flattening filter from the treatment head
      may reduce the beam-on time by enhancing the output dose rate, and then reduce
      the treatment delivery time. And in practice, there is a possibility of
      delivering the required fluence distribution by modulating the unflattened non
      uniform fluence distribution. However, the reduction of beam-on time may be
      discounted by the increase of leaf-travel time and (or) verification-and
      recording (V&R) time. Here we investigate the overall effect of flattening filter
      on the treatment delivery time of IMRT with MLCs implemented in the step and
      shoot method, as well as with compensators on six hybrid machines. We compared
      the treatment delivery time with/without flattening filter for ten nasopharynx
      cases and ten prostate cases by observing the variations of the ratio of the beam
      on time, segment number, leaf-travel time and the treatment delivery time with
      dose rate, leaf speed and V&R time. The results show that, without the flattening
      filter, the beam-on time reduces for both static MLC and compensator-based
      techniques: the number of segments and the leaf-travel time increase slightly for
      the static MLC technique; the relative IMRT treatment delivery time decreases
      more with lower dose rate, higher leaf speed and shorter V&R overhead time. The
      absolute treatment delivery time reduction depends on the fraction dose. It is
      not clinically significant at a fraction dose of 2 Gy for the technique of
      removing the flattening filter, but becomes significant when the fraction dose is
      as high as that for radiosurgery.

PMID- 15152689
TI  - Quantitative measurement of MLC leaf displacements using an electronic portal
      image device.
AB  - The success of an IMRT treatment relies on the positioning accuracy of the MLC
      (multileaf collimator) leaves for both step-and-shoot and dynamic deliveries. In
      practice, however, there exists no effective and quantitative means for routine
      MLC QA and this has become one of the bottleneck problems in IMRT implementation.
      In this work we present an electronic portal image device (EPID) based method for
      fast and accurate measurement of MLC leaf positions at arbitrary locations within
      the 40 cm x 40 cm radiation field. The new technique utilizes the fact that the
      integral signal in a small region of interest (ROI) is a sensitive and reliable
      indicator of the leaf displacement. In this approach, the integral signal at a
      ROI was expressed as a weighted sum of the contributions from the displacements
      of the leaf above the point and the adjacent leaves. The weighting factors or
      linear coefficients of the system equations were determined by fitting the
      integral signal data for a group of pre-designed MLC leaf sequences to the known
      leaf displacements that were intentionally introduced during the creation of the
      leaf sequences. Once the calibration is done, the system can be used for routine
      MLC leaf positioning QA to detect possible leaf errors. A series of tests was
      carried out to examine the functionality and accuracy of the technique. Our
      results show that the proposed technique is potentially superior to the
      conventional edge-detecting approach in two aspects: (i) it deals with the
      problem in a systematic approach and allows us to take into account the influence
      of the adjacent MLC leaves effectively; and (ii) it may improve the signal-to
      noise ratio and is thus capable of quantitatively measuring extremely small leaf
      positional displacements. Our results indicate that the technique can detect a
      leaf positional error as small as 0.1 mm at an arbitrary point within the field
      in the absence of EPID set-up error and 0.3 mm when the uncertainty is
      considered. Given its simplicity, efficiency and accuracy, we believe that the
      technique is ideally suitable for routine MLC leaf positioning QA.

PMID- 15152691
TI  - The effect of Monte Carlo statistical uncertainties on the evaluation of dose
      distributions in radiation treatment planning.
AB  - This paper discusses the effect of statistical uncertainties present in Monte
      Carlo (MC) calculated dose distributions on the evaluation of a 'cost function'
      that expresses the suitability of a treatment plan for the intended treatment.
      The mathematical derivations given are valid for any 'well-behaved' cost
      function. The validity of the general expressions is demonstrated using numerical
      examples. It is shown that random dose uncertainties lead to statistical and
      systematic uncertainties on the cost function. The balance between the two types
      of uncertainty and the desired accuracy on the cost function presents a clear
      criterion for the maximum acceptable MC dose uncertainties. It is demonstrated
      that it is possible to remove the systematic cost function uncertainty. Finally,
      it is shown that when the dose distribution is close to a true optimum, MC
      calculations of the cost function converge to the true result as one over the
      number of particles simulated, i.e. much faster than the individual dose
      uncertainties.

PMID- 15152692
TI  - Modelling an extreme water-lung interface using a single pencil beam algorithm
      and the Monte Carlo method.
AB  - The goal of this study was to quantify, in a heterogeneous phantom, the
      difference between experimentally measured beam profiles and those calculated
      using both a commercial convolution algorithm and the Monte Carlo (MC) method.
      This was done by arranging a phantom geometry that incorporated a vertical solid
      water-lung material interface parallel to the beam axis. At nominal x-ray
      energies of 6 and 18 MV, dose distributions were modelled for field sizes of 10 x
      10 cm(2) and 4 x 4 cm(2) using the CadPlan 6.0 commercial treatment planning
      system (TPS) and the BEAMnrc-DOSXYZnrc Monte Carlo package. Beam profiles were
      found experimentally at various depths using film dosimetry. The results showed
      that within the lung region the TPS had a substantial problem modelling the dose
      distribution. The (film-TPS) profile difference was found to increase, in the
      lung region, as the field size decreased and the beam energy increased; in the
      worst case the difference was more than 15%. In contrast, (film-MC) profile
      differences were not found to be affected by the material density difference.
      BEAMnrc-DOSXYZnrc successfully modelled the material interface and dose profiles
      to within 2%.

PMID- 15152693
TI  - The radial dose function of low-energy brachytherapy seeds in different solid
      phantoms: comparison between calculations with the EGSnrc and MCNP4C Monte Carlo
      codes and measurements.
AB  - The use of low-energy photon emitters for brachytherapy applications, as in the
      treatment of the prostate or of eye tumours, has drastically increased in the
      last few years. New seed models for 103Pd and 125I have recently been introduced.
      The American Association of Physicists in Medicine recommends that measurements
      are made to obtain the dose rate constant, the radial dose function and the
      anisotropy function. These results must then be compared with Monte Carlo
      calculations to finally obtain the dosimetric parameters in liquid water. We have
      used the results obtained during the characterization of the new InterSource
      (furnished by IBt, Seneffe, Belgium) palladium and iodine sources to compare two
      Monte Carlo codes against experiment for these low energies. The measurements
      have been performed in three different media: two solid water plastics, WT1 and
      RW1, and polymethylmetacrylate. The Monte Carlo calculations were made using two
      different codes: MCNP4C and EGSnrc. These codes use photon cross-section data of
      a different origin. Differences were observed between both sets of input data
      below 100 keV, especially for the photoelectric effect. We obtained differences
      in the radial dose functions calculated with each code, which can be explained by
      the difference between the input data. New cross-section data were then tested
      for both codes. The agreement between the calculations using these new libraries
      is excellent. The differences are within the statistical uncertainties of the
      calculations. These results were compared with the experimental data. A good
      agreement is reached for both isotopes and in the three phantoms when the
      measured values are corrected for the presence of the TLDs in the phantom.

PMID- 15152694
TI  - Evaluation of temperature distributions in cadaveric lumbar spine during
      nucleoplasty.
AB  - In this study, temperature maps were obtained throughout human cadaveric disc
      specimens (n = 6) during a simulated Nucleoplasty treatment. The procedure was
      performed using the Perc-DL SpineWand (ArthroCare, Sunnyvale, CA) inserted
      through a 17 gage needle into the human cadaveric disc. The device uses a dual
      mode heating technique which employs a high voltage radio frequency (RF) plasma
      field to vaporize tissue (Coblation), followed by bipolar RF current heating for
      thermal coagulation. The device, with a distal 's-curve', is manipulated manually
      to create a series of six channels at a 60 degrees angular spacing within a
      period of 3 min. A computer-controlled, motorized translational system was used
      to reproducibly mimic the insertion (Coblation) and retraction (rf-coagulation)
      performed during clinical implementation, with rotation performed manually
      between each Coblation/coagulation cycle. Transient temperature data were
      obtained using five multi-junction thermocouple probes (5-8 junctions spaced at
      either 2 or 5 mm intervals, with 0.33 or 0.56 mm probe diameter) spaced
      throughout the desired heating volume. Transient temperature curves were obtained
      from 26+ points throughout the disc, and the data used to calculate accumulated
      thermal doses. Transient peaks of 80-90 degrees C were recorded within the discs,
      with temperatures greater than 60-65 degrees C measured within a radial distance
      of 3-4 mm from the introducer (applicator centreline). Accumulated thermal doses
      of t43 > 250 min were produced at radial distances of up to 6 mm from the
      introducer. Gross inspection of the discs revealed a narrow region of coagulation
      along the insertion length. Given these radial thermal penetrations and the
      possibility for unpredictable positioning during current clinical implementation,
      high temperatures and lethal thermal doses in small regions outside of the
      nucleus, or within the bone endplates, may be possible in clinical
      implementation.

PMID- 15152695
TI  - Correction for dose-response variations in a scanning liquid ion chamber EPID as
      a function of linac gantry angle.
AB  - The response of electronic portal imaging devices (EPIDs) of the scanning liquid
      ionization chamber (SLIC) type is known to vary with linear accelerator gantry
      angle. This work considered several contributing factors, quantified the
      artefacts, monitored their reproducibility and investigated the effects of
      repeated gantry rotations. Unflatness of up to 5% was found. A correction
      technique was devised using nonlinear regression of a three-variable sinusoidal
      modulation. Comparison with two existing techniques found our method to be the
      most effective, providing a flatness well within 2%. This improved accuracy is
      expected to benefit more accurate dosimetric studies in particular. The post
      acquisition correction process required no change in imaging protocols.
      Applicability of the new technique was demonstrated on images acquired on
      different days and with different beam sizes. Since the artefacts compromise both
      accurate dosimetry and image quality, their successful removal should benefit a
      broad range of SLIC EPID applications.

PMID- 15152696
TI  - Calibration of low-energy electron beams from a mobile linear accelerator with
      plane-parallel chambers using both TG-51 and TG-21 protocols.
AB  - A new approach to intraoperative radiation therapy led to the development of
      mobile linear electron accelerators that provide lower electron energy beams than
      the usual conventional accelerators commonly encountered in radiotherapy. Such
      mobile electron accelerators produce electron beams that have nominal energies of
      4, 6, 9 and 12 MeV. This work compares the absorbed dose output calibrations
      using both the AAPM TG-51 and TG-21 dose calibration protocols for two types of
      ion chambers: a plane-parallel (PP) ionization chamber and a cylindrical
      ionization chamber. Our results indicate that the use of a 'Markus' PP chamber
      causes 2-3% overestimation in dose-output determination if accredited dosimetry
      calibration laboratory based chamber factors (N(60Co)(D,w,) Nx) are used.
      However, if the ionization chamber factors are derived using a cross-comparison
      at a high-energy electron beam, then a good agreement is obtained (within 1%)
      with a calibrated cylindrical chamber over the entire energy range down to 4 MeV.
      Furthermore, even though the TG-51 does not recommend using cylindrical chambers
      at the low energies, our results show that the cylindrical chamber has a good
      agreement with the PP chamber not only at 6 MeV but also down to 4 MeV electron
      beams.

PMID- 15152697
TI  - Wavelet analysis of blood flow dynamics: effect on the individual oscillatory
      components of iontophoresis with pharmacologically neutral electrolytes.
AB  - Iontophoresis currents are used in the transcutaneous delivery of vasoactive
      substances for noninvasive assessment of skin vascular properties. The blood flow
      rate can be recorded by laser Doppler flowmetry (LDF), its average value and the
      amplitudes of its oscillatory components being used to evaluate the effect of the
      drugs. Because non-drug-specific, current-induced, vasodilation could confound
      the interpretation of the response, we have investigated the effect of currents
      of both polarities on the spectral components of the LDF signal in the absence of
      vasoactive substances. It was recorded for healthy volunteers with both high
      conductance (5 mol/l NaCl) and low conductance (deionized water) electrolytes.
      The oscillatory components were analysed by wavelet transform within 0.0095-1.6
      Hz, divided into five sub-intervals. Only cathodal iontophoresis with deionized
      water increased the oscillatory energy and amplitude. It did so at all
      frequencies, but none of the sub-intervals associated with vasodilation (0.0095
      0.145 Hz) was selectively affected compared to the others.

PMID- 15152698
TI  - Economic analysis in healthcare decisions.

PMID- 15152699
TI  - An illness in the family: accounting for the complex effects of illness on other
      family members.

PMID- 15152700
TI  - Why don't Americans use cost-effectiveness analysis?
AB  - Cost-effectiveness analysis (CEA) offers decision makers a structured, rational
      approach with which to improve the return on resources expended. But decades
      after its widespread promotion to the medical community, policy makers in the
      United States remain reluctant to use the approach formally. Indeed, the
      resistance to economic evidence in the United States in an era of evidence-based
      medicine in healthcare is perhaps the most notable development of all. This paper
      examines the resistance to CEA in the United States and explores ways in which to
      advance the field.

PMID- 15152701
TI  - The family impact and costs of migraine.
AB  - OBJECTIVE: To obtain information on migraine and its impact on the family,
      particularly on the healthcare utilization and productivity of family members
      without migraine. STUDY DESIGN: Retrospective study using linked medical and
      pharmacy claims data that allowed identification of families and individuals with
      migraine. PATIENTS AND METHODS: Families with at least 1 migraineur were matched
      with up to 3 nonmigraineur families on employer, age of migraineur, number of
      family members, sex, and index date quarter. For a subset of employees, data on
      short- and long-term disability as well as absenteeism also were evaluated to
      determine the impact of migraine on these indirect costs. RESULTS: The total
      healthcare costs of a family with a migraineur were 70% higher than those of the
      nonmigraine family, with most of the difference concentrated in outpatient costs.
      The impact of having a migraineur in the family persisted even after controlling
      for other disorders and demographics in a multivariate model. Total healthcare
      costs per family depended on which family member was the migraineur, and were
      about dollars 600 higher when the sole migraineur was a child versus a parent and
      almost dollars 2500 higher when both a parent and child were affected (compared
      with families in which the sole migraineur was a child). Work absence days, short
      term disability, and workman's compensation days all were higher among migraine
      families than among families without a migraineur. CONCLUSION: Migraine families
      incur far higher direct and indirect healthcare costs than nonmigraine families,
      with variation depending on which family member is the clinically detected
      migraineur.

PMID- 15152702
TI  - Predicting patient-reported asthma outcomes for adults in managed care.
AB  - OBJECTIVE: To develop and evaluate a set of questionnaire-based screening tools
      to identify risk for 1-year adverse outcomes in adults with moderate to severe
      asthma. STUDY DESIGN: Prospective cohort study in 16 managed care organizations
      in the United States. PATIENTS AND METHODS: Patients (n = 4888) with moderate-to
      severe asthma completed baseline and 1-year questionnaires (response rate, 79%).
      Adverse outcomes included hospitalization in the past year; emergency department
      (ED) visit in the past year; days of lost activity in the past month; a composite
      measure combining hospitalization, ED use, and lost days; and severe symptoms.
      Risk models were constructed for each of these 5 outcomes. Candidate predictors
      included baseline demographic characteristics, prior asthma healthcare use,
      access to care, symptoms, and treatment. Outcome variables were dichotomized, and
      logistic regression analysis was used to estimate the probability of 1-year
      outcomes. RESULTS: The patients' mean age was 45 years; 69% were female, and 83%
      were white. At 1-year follow-up, 9% had been hospitalized in the past year, 35%
      had used the ED, and 36% had reduced activity in the past month; 54% reported at
      least 1 of these, and 53% reported severe symptoms. Twenty-one items were
      retained for the 5 final risk models. Overall, the strongest predictors were
      comorbid illnesses and prior ED use. Model discrimination using receiver
      operating characteristic area ranged from 0.67 to 0.78 for predicting
      hospitalization, ED use, lost days, any one of these outcomes, and symptoms.
      CONCLUSIONS: The questionnaire-based risk models identified with good
      discrimination asthmatics at increased risk for a range of adverse outcomes. Risk
      models based on patient-reported data could be used to target individuals for
      intervention.

PMID- 15152703
TI  - Use of formal benefit/cost evaluations in health system decision making.
AB  - OBJECTIVES: To examine actual use of formal benefit/cost and benefit/risk results
      in health system decision making by public and private healthcare organizations.
      STUDY DESIGN: A direct survey with questions about healthcare decisions made by
      the respondent or the respondent's organization. The scope of this survey
      precluded meaningful quantitative analysis, thus descriptive and qualitative
      analyses were performed. PARTICIPANTS AND METHODS: An initial questionnaire was
      tested in 2001 with 15 respondents in 4 countries. In 2002, a revised
      questionnaire was sent to a convenience sample of 116 individuals representing
      information users (providers, payers, and regulators) and information producers
      (technology firms and academics) in France, Sweden, the United Kingdom, and the
      United States. Responses were received from 104 people (89.7%). RESULTS: Every
      information user employed benefit/risk analyses to accept or reject new
      interventions and delete existing technologies. In addition, 42.1% of information
      users also used formal benefit/cost results (cost effectiveness, cost benefit,
      and/or cost utility). Seven providers/payers in the United States, 1 in France,
      and 1 in the United Kingdom required such analyses, as did 1 UK regulator. Most
      did not produce their own analyses but relied on those of public organizations
      (eg, Food and Drug Administration, National Institute of Clinical Effectiveness),
      academics, and pharmaceutical firms. CONCLUSIONS: A surprisingly high percent of
      information users (42.1%) employed any formal economic cost-effectiveness, cost
      benefit, or cost utility analysis, CEA, CBA, or CUA evaluations in deciding
      whether to accept, pay for, or reject new interventions or to delete old
      interventions. Still, this figure was substantially higher than expected given
      the results of previous studies, nearly all of which found low use of formal
      benefit/risk and benefit/cost analyses.

PMID- 15152704
TI  - Assessing symptoms, disease severity, and quality of life in the clinical
      context: a theoretical framework.
AB  - Health-related quality-of-life instruments can yield important health information
      that is often distinct from objective measures of symptoms and disease severity
      that clinicians are most attuned to. Comprehensive health assessment can be
      difficult because there are many available measurement instruments that vary in
      their scope and content. The conceptual boundaries between symptom, disease
      severity, and health-related quality-of-life instruments are frequently blurred
      in practice, and what is measured may not coincide with clinical and research
      goals. The Assessing the Impact of Disease framework aims to clarify the process
      of selecting appropriate assessment instruments. Three common diseases are
      discussed in depth to illustrate the applicability of Assessing the Impact of
      Disease in distinguishing between symptom, severity, and health-related quality
      of-life measurements.

PMID- 15152705
TI  - Pretreatment illegal activities of a nationwide sample of adolescent substance
      abuse clients.
AB  - While much is known about criminal behavior patterns of general population and
      delinquent youth, little is known about the pretreatment criminality of
      adolescent substance abuse treatment clients. This information is important
      because of substantial increases in adolescent substance abuse treatment
      admissions and because adolescents who use substances regularly are more likely
      than nonusers to be criminally involved. Descriptive information is presented on
      the lifetime patterns of substance abuse, criminal activity, and justice system
      involvement of 1,122 youth admitted to nine adolescent treatment programs located
      throughout the United States, including short- and long-term residential and
      outpatient programs. Study findings indicate that involvement in illegal
      activities, other than use and possession of substances, is common among
      adolescents entering treatment. Most clients in each modality were involved with
      the justice system prior to treatment, and pressure from the justice system to
      enter treatment was widely reported. While the severity and frequency of offenses
      committed by short- and long-term residential clients were considerably greater
      than outpatient clients, a sizable minority of outpatient clients had also
      committed serious offenses. In addition to differences among modalities,
      considerable variation in criminal involvement was found among programs within
      the same modality. Implications for treatment and research are discussed.

PMID- 15152706
TI  - Gender differences in substance use, mental health, and criminal justice
      involvement of adolescents at treatment entry and at three, six, twelve and
      thirty month follow-up.
AB  - Many adolescents entering substance abuse treatment have coexisting mental health
      problems and are criminally involved. Examination of the complexities of
      substance use, mental health, and criminal justice involvement along with changes
      in these issues following treatment is needed. This study includes 941 males and
      266 females enrolled in seven drug treatment programs located in geographically
      diverse areas of the United States. Comparisons between males and females at
      treatment entry and three, six, 12 and 30 months later were examined with regard
      to substance use, mental health, and criminal justice involvement. Results
      indicate that females showed significantly greater severity in substance use,
      problems associated with use, and mental health related variables at intake while
      males had significantly more days on probation/parole. With respect to change
      over time, the rate of change in mental health and days on probation/parole
      differed between the sexes. Results indicate that while rate of change is
      different for males and females on most variables, there was positive change
      following treatment for both groups with regard to substance use, mental health,
      and probation/parole status. The high severity levels of females at intake calls
      for gender-specific outreach and identification along with gender-specific
      treatments.

PMID- 15152707
TI  - Assessing the effectiveness of community-based substance abuse treatment for
      adolescents.
AB  - The Adolescent Treatment Models initiative, a 10-site, multimodality, prospective
      study, was designed to evaluate adolescent substance abuse treatment outcomes and
      to assess the relative efficacy of different treatment models. Based upon
      longitudinal data gathered at multiple assessment points using a standardized
      instrument, treatment outcome trajectories were determined for a cohort of 1,057
      adolescents from entry into substance abuse treatment until 12 months post
      intake. Client outcomes on substance use and program effectiveness were explored
      across individual treatment programs and levels of care. Strong treatment
      effects, defined as a significant reduction in alcohol and other drug use at
      three months post-intake, were found. The reductions of greatest magnitude in
      relation to pretreatment use occurred among adolescents in residential treatment.
      Within level of care, few significant differences in treatment effects were found
      between programs. Relapse effects, defined as an increase in substance use at 12
      months relative to three months, were observed across nearly all programs, but
      varied in relation to treatment modality. This is most evident among those
      entering residential treatment, with the highest rate of relapse occurring among
      adolescents in long-term residential treatment care. Despite strong evidence of
      treatment effectiveness, continuing care is vital to maintenance of treatment
      benefit.

PMID- 15152708
TI  - Comparing outcomes of best-practice and research-based outpatient treatment
      protocols for adolescents.
AB  - Comparisons of well-developed practice-based interventions with research-based
      interventions are rare. This quasi-experimental study compares the outcomes of
      274 adolescents (75% male; 63% weekly+ users; 54% dependent; 27% prior treatment;
      73% with co-occurring problems) who received Chestnut Health System's best
      practice Outpatient Treatment (CHS) or Cannabis Youth Treatment (CYT) research
      based interventions. Ninety-five percent of participants completed follow-up
      interviews at three, six, nine, and 12 months after their intake GAIN interview.
      Initially, the CYT cohort scores indicated greater severity on several substance
      related measures, while the CHS cohort scored higher on prior mental health
      treatment, victimization, and illegal activities measures. Adolescents in the CHS
      cohort were more likely to have longer lengths of stay and receive over three
      times as many hours of treatment. Mixed effects models revealed that CHS
      participants were significantly more likely to report a decrease in recovery
      environment risk, an increase in self-help attendance after treatment, and
      greater decreases in emotional problems, while CYT participants were
      significantly more likely to report decreases in their substance use. The results
      suggest that neither the best-practice nor the research-based interventions were
      clearly superior and call for a more rigorous randomized field experiment to
      better understand the differences in effectiveness between interventions.

PMID- 15152709
TI  - Early intervention for adolescent substance abuse: pretreatment to posttreatment
      outcomes of a randomized clinical trial comparing multidimensional family therapy
      and peer group treatment.
AB  - This randomized clinical trial evaluated a family-based therapy and a peer group
      therapy with 80 urban, low-income, and ethnically diverse young adolescents (11
      to 15 years) referred for substance abuse and behavioral problems. Both
      treatments were outpatient, relatively brief, manual-guided, equal in
      intervention dose, and delivered by community drug treatment therapists.
      Adolescents and their parents were assessed at intake to treatment, randomly
      assigned to either MDFT or group therapy, and reassessed at six weeks after
      intake and at discharge. Results indicated that the family-based treatment (MDFT,
      an intervention that targets teen and parent functioning within and across
      multiple systems on a variety of risk and protective factors) was significantly
      more effective than peer group therapy in reducing risk and promoting protective
      processes in the individual, family, peer, and school domains, as well as in
      reducing substance use over the course of treatment. These results, which add to
      the body of previous findings about the clinical and cost effectiveness of MDFT,
      support the clinical effectiveness and dissemination potential of this family
      based, multisystem and developmentally-oriented intervention.

PMID- 15152710
TI  - Adolescent and parent perceptions of outpatient substance abuse treatment: a
      qualitative study.
AB  - This exploratory study used in-depth interviews with 12 adolescent participants
      and four parents to describe their perceptions of outpatient substance abuse
      treatment. Adolescents found treatment to be different than they had expected,
      expressed preferences for different session formats (group, individual, family),
      and defined treatment success in different ways than their parents. There were no
      common themes regarding what adolescents and parents liked best or least about
      treatment. Findings suggest several implications for treatment providers and
      areas for future study: (a) the need to provide detailed descriptions of
      treatment to referral sources and orientation for adolescents and their parents
      prior to entry; (b) the need to make skill-building sessions interesting and
      limit their repetition; (c) the need to group adolescents by severity or problem
      type; (d) the need for flexibility and assertive outreach to improve family
      involvement in treatment; and (e) the need to provide adolescent treatment
      consumers and their parents with data regarding treatment success from a number
      of perspectives (e.g. substance use, associated problems, school performance).
      This study illustrates that adolescents and their parents are important sources
      of information about the treatment experience and may provide useful ideas for
      enhancing treatment engagement and retention.

PMID- 15152712
TI  - Clinical characteristics and treatment outcomes of adolescent heroin users.
AB  - Heroin use among adolescents is a major social and health problem, and has been
      increasing over the past decade, but has not been extensively studied. This study
      compared characteristics of adolescent heroin users (n = 56) to adolescent non
      heroin users (n = 93) at entry to short-term residential treatment through 12
      months posttreatment. The heroin group was comprised of more females, older
      adolescents, and more Caucasians. At baseline, heroin users reported more days of
      drug use, days high, days not meeting responsibilities, and had more substance
      abuse and dependence symptoms. Heroin users also showed greater severity on
      multiple indicators of functional impairment and psychological distress. Although
      adolescent heroin users appear to represent a distinct subpopulation with
      multiple indicators of heightened severity, they respond to treatment with
      significant reductions in drug use, psychological symptoms, illegal activities,
      and overall psychosocial impairment. Furthermore, adolescent heroin users respond
      to treatment in the same remitting/relapsing pattern as non heroin users, yet
      their higher severity persists over a 12 month follow-up period. Further research
      is needed to generalize these findings to other settings, and to guide the
      development and evaluation of treatment options for adolescent heroin users.

PMID- 15152711
TI  - Adolescent and young adult heroin and non heroin users: a quantitative and
      qualitative study of experiences in a therapeutic community.
AB  - Admissions to treatment for heroin abuse have increased in recent years among the
      adolescent and young adult population, yet few studies have described whether,
      and to what extent, young heroin users differ from their non heroin-using peers.
      This exploratory study presents quantitative and qualitative data obtained from
      lifetime heroin and non heroin-using adolescents and young adults in a long-term,
      step-down therapeutic community. Self-report data from the Global Appraisal of
      Individual Needs (GAIN) were obtained from 22 lifetime heroin and 33 non heroin
      users on admission to residential treatment and 12 months later. Ethnographic
      interviews (n = 27) were conducted with heroin users at all stages of treatment.
      Results indicate that lifetime heroin users had greater polysubstance use and
      lower self-efficacy scores (i.e., confidence to resist relapse) on admission to
      treatment than non heroin users, and though improved, heroin users' self-efficacy
      scores remained lower than those of non heroin users at the 12 month follow-up.
      Ethnographic data suggested that adolescents who had used heroin "hit bottom"
      before entering treatment and credited treatment with providing the opportunity
      to change their lives. The overall comparability of treatment outcomes between
      the heroin and non heroin using groups shows that adolescents and young adult
      heroin users can achieve similar outcomes in an age-appropriate therapeutic
      community treatment setting.

PMID- 15152713
TI  - Bradycardia induced by hyperkalemia.
AB  - The incidence of chronic cardiac disease is increasing (Jessup, 2003). As a
      result, it is important for occupational health nurses to recognize adverse
      effects (e.g., electrolyte abnormalities, dysrhythmias) associated with current
      treatment guidelines (Hunt, 2001). As shown in the example in this case study,
      the current recommended treatment for clients who have myocardial ischemia and
      left ventricular dysfunction (i.e., ACE inhibitor and a potassium-sparing
      diuretic) puts clients at risk for hyperkalemia, especially in the presence of
      renal insufficiency.

PMID- 15152714
TI  - Developing more effective workplace interventions--use of the Precede-Proceed
      model.

PMID- 15152715
TI  - Special focus: international perspectives--exploring the world through
      international occupational health programs.

PMID- 15152717
TI  - SARS update: Winter, 2003 to 2004.
AB  - Transmission of severe acute respiratory syndrome (SARS) related coronavirus
      (CoV) appears to be heterogeneous. Most transmission occurs through large
      droplets, but there is some evidence of spread through aerosol transmission.
      Proper use of personal protective equipment (PPE) and scrupulous attention to
      hand hygiene are critical to reducing transmission of SARS, especially in health
      care facilities. Surgical masks have been shown to be highly effective in
      reducing transmission when N-95 respirators are unavailable. Health care workers
      bore a large burden of illness during the 2002 to 2003 SARS epidemic.
      Occupational health nurses working in health care agencies will play a key role
      in preparing for a re-emergence of the disease. Occupational health nurses should
      "bookmark" the Centers for Disease Control and Prevention website for Public
      Health Guidance for Community-Level Preparedness and Response to SARS:
      www.cdc.gov/ncidod/sars/clinicalguidance.htm for easy retrieval and reference.

PMID- 15152716
TI  - Occupational health nursing in Lebanon: exploring the world through international
      occupational health programs.
AB  - Lebanon is undergoing rapid developments. The majority of occupations
      (approximately two thirds) fall under services, industry makes up one fifth, and
      the remaining occupations are in agriculture. Primary health care is recently
      gaining renewed interest, with a focus on primary preventive services.
      Occupational health practice lags behind, despite the presence of legislation.
      Data related to occupational illnesses and injuries are fragmented. There is need
      for comprehensive multidisciplinary national studies to identify occupational
      health needs. Occupational health nursing is underdeveloped in Lebanon.
      Nevertheless, the establishment of a National Nurses' Order is hoped to promote
      the educational preparation and scope of nursing practice in the field.

PMID- 15152718
TI  - Workplace violence against K-12 teachers: implementation of preventive programs.
AB  - Decreasing both workplace and school violence needs to be a priority of
      individuals, families, communities, and workplaces for the effort to be
      successful. Key factors associated with school and workplace violence such as
      parental influences, school staff and police involvement, peer pressure, student
      influences such as drug and alcohol abuse and a preoccupation with weapons, and
      the mass media have all been identified as possible factors associated with
      violence against teachers. In addition, individual student characteristics such
      as gender, socioeconomic status, and a history of prior violence may play a role.
      However, none of these factors can be identified or singled out as the reason for
      violence. Violence against teachers occurs as a result of a combination of these
      factors. Understanding how these factors interact should be a goal of every
      community and school. Occupational health nurses have the unique opportunity to
      partner with communities, school nurses, and the school system to develop
      effective violence prevention programs. Working in schools is an area of
      expansion for occupational health nurses. They have the expertise to perform
      worksite assessments and to identify key areas of weakness throughout the
      facility. Their expertise in reviewing and analyzing workplace injury data and
      developing cost effectiveness analysis for proposed interventions is unique.
      Occupational health nurses also have the skills to network with school officials
      and other key stakeholders to develop interventions to impact the substantial
      implications of violence in the schools.

PMID- 15152719
TI  - Hepatitis C: an update for occupational health nurses.
AB  - Hepatitis C is no longer an emerging dilemma. It is a significant public health
      problem with life altering complications. Occupational health nurses have the
      responsibility to their employees to be up to date on the latest treatment
      modalities so they can accurately advise their clients should an exposure occur.
      Occupational health nursing practice needs to focus on employee education related
      to Occupational Safety and Health Administration's Blood Borne Pathogens Standard
      and the latest in safety devices through regular yearly in-services.

PMID- 15152720
TI  - Workplace bullying.

PMID- 15152721
TI  - Translations.

PMID- 15152722
TI  - Occupational therapy in the field of mental health: promoting occupational
      perspectives on health and well-being.

PMID- 15152723
TI  - Occupational justice and client-centred practice: a dialogue in progress.
AB  - BACKGROUND: This paper describes an ongoing, international dialogue about the
      relationship between occupation, justice, and client-centred practice, prompted
      by the question: How do occupational therapists work for justice? METHODS: The
      authors critically reflect on their own dialogue and culturally situated
      interests, dialogues with workshop participants, and a literature review.
      RESULTS: Four cases of occupational injustice are proposed: occupational
      alienation, occupational deprivation, occupational marginalization, and
      occupational imbalance. The naming of these occupational injustices suggests four
      occupational rights: to experience meaning and enrichment in one's occupations;
      to participate in a range of occupations for health and social inclusion; to make
      choices and share decision-making power in daily life; and to receive equal
      privileges for diverse participation in occupations. PRACTICE IMPLICATIONS: Since
      silence implies compliance with the status quo, the authors encourage
      occupational therapists to develop their own dialogue about occupational
      injustices in order to address them openly with others. Dialogue about
      occupational justice is timely as occupational therapists around the world
      articulate what distinguishes this numerically small, rather invisible profession
      and its contributions to individuals, populations, and societies.

PMID- 15152724
TI  - Life care plans: an emerging area for occupational therapists.
AB  - BACKGROUND: Life care plans, or cost of future care reports as they are often
      called in Canada, are medico-legal documents that predict probable future medical
      and rehabilitation needs and costs. They are used when someone has sustained a
      serious personal injury in an accident, as the result of medical malpractice, or
      due to some other unnatural cause. Life care plans are generally commissioned by
      third-party payers in order to set aside adequate reserves for future costs or to
      negotiate a settlement. SCOPE: Life care plans need to be grounded in knowledge
      of how personal injury law has been applied and interpreted. Therefore, Canadian
      law pertaining to the costs of future care in personal injury will be briefly
      reviewed. The balance of the article discusses the process used to develop a life
      care plan, the necessary content, and accepted formats for reports. The article
      concludes with a case example that demonstrates the application of life care
      planning skills. PRACTICE IMPLICATIONS: Occupational therapists are well suited
      to developing these plans by virtue of their training, knowledge base, and
      theoretical approaches. This is an emerging consultative role for experienced
      therapists.

PMID- 15152725
TI  - Can I play too? Physical activity engagement of children with developmental
      coordination disorders.
AB  - BACKGROUND: Children with developmental coordination disorders (DCD) are less
      physically active and have significantly different patterns of social and
      physical play than their well-coordinated peers. FACTORS: The impact of motor
      incoordination on physical activity engagements throughout life is influenced by
      a multitude of factors. External factors such as the social, cultural and
      physical environment may act as either supports or barriers to active physical
      involvement. Individual characteristics including the unique physical and
      psychological attributes of the child with motor coordination difficulties also
      impact on engagement in physically active occupations. RESULT: A model is
      proposed that conceptualizes the multiple dimensions which impinge on the
      decisions to select, engage and persist in physical activities for children with
      developmental coordination disorders. PRACTICE IMPLICATIONS: The occupational
      therapist's role in promoting a balanced and physically active lifestyle is
      explored. Interventions to increase physical activity participation for children
      with DCD are dependent on a full understanding of the complex, multi-dimensional
      correlates of occupational engagement.

PMID- 15152726
TI  - [The use of theatre in the psychosocial readaptation of patients with mental
      disorders: participants' perspectives].
AB  - BACKGROUND: Therapy using theatrical activity was proposed to six clients with
      severe and persistent mental health problems. The purpose of this study was to
      determine what meaning the participants attributed to this experience and which
      aspects of the therapy they considered influential for their progress. METHOD: A
      formal approach, based on the opinions of the actors, was used in order to
      optimize the quality of the interventions. The application was as closely linked
      as possible to a real theatrical experience. An analysis of the qualitative data
      collected from a questionnaire and a semi-structured interview of three subjects
      selected from a purposive sampling was done by way of successive cycles of data
      reduction. RESULTS AND PRACTICE IMPLICATIONS: The participants valued the
      flexibility and versatility of the theatrical experience. They perceived the
      presence of the public as essential to enhancing their experience of pleasure and
      personal competency. Therapy using theatrical activity appears to be relevant in
      the field of psychosocial rehabilitation.

PMID- 15152727
TI  - Healthy occupation and disability management services.

PMID- 15152728
TI  - Quality occupational therapy services.

PMID- 15152729
TI  - Don't trust an LDL over 70?

PMID- 15152730
TI  - Screening and brief interventions for alcoholism.

PMID- 15152731
TI  - Solitary, marginated ulceration on right lateral leg.

PMID- 15152732
TI  - Psychomotor disadaptation syndrome. A new clinical entity in geriatric patients.
AB  - Psychomotor Disadaptation Syndrome (PDS) is characterized by backward
      disequilibrium in a sitting and standing position, reactional hypertonia, an
      alteration of postural reactions, gait modifications, and fear of falling. PDS
      may be the result of a loss of postural reserves, reaching a frailty threshold
      that does not allow subjects to maintain an adequate functional level. This
      clinical picture may be associated with frontal-subcortical dysfunction in which
      microangiopathy could play a key role. PDS may be triggered by numerous factors,
      such as cardiovascular and metabolic diseases, falls, and bed rest. In addition
      to medical and neurological evaluations, a specific rehabilitation program is one
      of the most important aspects of the management of patients showing PDS.

PMID- 15152733
TI  - The psychosocial aspects of diabetes care. Using collaborative care to manage
      older adults with diabetes.
AB  - Diabetes is a chronic disease that requires managing medications, adhering to
      dietary requirements, and engaging in age- and abilities appropriate physical
      activity. This article addresses the need for a collaborative care management
      approach that emphasizes a partnership between older adults and health care
      professionals. Such an approach recognizes that patients are the experts about
      their lives and primary care providers are experts about diabetes. A
      collaborative care management approach can help primary care providers assist
      older adults to address psychosocial concerns, cognitive functioning, and
      depression. We conclude this article with a brief discussion regarding a
      transdisciplinary approach that takes the collaborative care management approach
      one step further.

PMID- 15152734
TI  - Estrogen ring use for genitourinary atrophy and menopausal symptomatology.

PMID- 15152735
TI  - Sharing the diagnosis of Alzheimer's disease: methods and expectations. Breaking
      news to patients requires patience and sensitivity to their needs.

PMID- 15152736
TI  - Seated toe point and flex.

PMID- 15152737
TI  - Wisdom in the fourth age: viewing aging with optimism.

PMID- 15152738
TI  - Evidence-based protocol. Treatment of pressure ulcers.
AB  - Those who provide direct care to older adults with pressure ulcers play a
      significant role in ensuring the environment is optimal for wound healing. Use of
      the evidence-based guideline "Treatment of Pressure Ulcers" (Folkedahl, Frantz &
      Goode, 2002b) can provide a template for implementation of interventions to
      maximize the repair process.

PMID- 15152739
TI  - Depression and social support: effective treatments for homebound elderly adults.
AB  - Assessment of depression in homebound elderly adults is crucial because
      depression affects quality of life, mortality, and health care costs. The
      prevalence of depression in homebound elderly adults is estimated to range from
      26% to 44% (Banerjee, Shamash, Macdonald, & Mann, 1996). Review of the literature
      indicates that depression is a common problem among elderly individuals; and
      elderly individuals can benefit from prompt treatment. This pilot study assessed
      the prevalence of depression in 25 homebound elderly adults in the Chicago area
      and the relationship of depression to perceived level of social support, measured
      using Yesavage and Brink's (1983) Geriatric Depression Scale (GDS), Sarason,
      Sarason, Shearin, and Pierce's (1987) Social Support Scale, and a checklist of
      formal services received in the home. The study was conducted in the homes of 25
      home health patients. This pilot study found 52% (13) of the participants scored
      in the moderately depressed range on the GDS. Although satisfaction with
      individuals who provide social support was rated highly by all participants, the
      level of support was not significantly related to depression. Formal measures of
      social support and living alone were not found to be related to depression in
      this study. Depression was higher in White men. These findings have implications
      for the increased monitoring of depression by home health nurses and other
      primary care providers to homebound elderly adults.

PMID- 15152740
TI  - Contemplating, caring, coping, conversing: a model for promoting mental wellness
      in later life.
AB  - This article is based on the premise that mental wellness for older adults can be
      promoted through communication and presents a model drawing on the constructs of
      contemplating, caring, coping, and conversing. The importance of interpersonal
      communication processes in the care of older adults and some barriers to
      communication and mental wellness are briefly reviewed. This article challenges
      nurses to develop awareness of their own caregiving styles and communication
      processes, and to assist others (e.g., family caregivers, care receivers) to
      communicate and interact more effectively to advance mental wellness for older
      adults.

PMID- 15152741
TI  - Pain treatment and quality of life: reducing depression and improving cognitive
      impairment.
AB  - The purpose of this study was to identify implications for the care of nursing
      home residents based on exploration of the relationship of depression to pain,
      cognitive impairment, and communication impairment in this population. A
      descriptive, cross-sectional, post-hoc design was used. Methods of statistical
      analysis included bivariate correlation coefficient calculation, stepwise
      multiple regression, and analysis of variance. A complex triad of cognitive
      impairment, pain, and depression was identified. The strength of the relationship
      between depression and cognitive impairment increases as cognitive impairment
      increases and in the presence of pain. This relationship is strongest among
      residents with severe cognitive impairment, severe communication impairment, and
      advanced age. Nurses may be able to relieve symptoms of depression in nursing
      home residents by using strategies based on knowledge of the resident's
      cognitive, communication, and pain status. Treating pain may lead to improved
      cognitive performance in residents who are depressed or reduced depression in
      residents who are cognitively impaired. The most elderly adults and adults with
      severe communication impairment may benefit most from these interventions.

PMID- 15152742
TI  - Decreasing assault occurrence on a psychogeriatric ward: an agitation management
      model.
AB  - An agitation management model providing staff education, quantitative assessment
      of agitation, and emphasized psychosocial interventions was introduced on a
      geriatric psychiatry ward for male patients. A within-subjects comparison was
      made of Cohen-Mansfield Agitation Inventory (CMAI) scores and frequency of
      committing assault under pre- and post-intervention conditions. Among
      participants (N = 8) who finished the 72-week study, CMAI scores did not differ
      significantly under either of the study conditions (p > .05, two-tailed t test).
      Twenty-nine assaults occurred during the pre-intervention time period and six
      assaults occurred during the post-intervention time period. According to analysis
      with the Wilcoxon signed ranks test, the distribution of assaults differed
      significantly between the two time periods (p < .05, two-tailed). Among
      individuals who were excluded from the intervention because of lack of consent,
      assaults increased over the same two time periods. Psychosocial interventions
      intended to reduce agitation among elderly men with dementia may not necessarily
      serve to decrease agitation, but may serve to decrease assault occurrence.

PMID- 15152743
TI  - Caring for self while caring for others: the two-track life of coping with
      Alzheimer's disease.
AB  - Relationships between depressive symptoms and altered immune function have been
      documented in the literature; however, the links between depressive symptoms,
      altered immune function, and changes in physical health are less clear. Although
      a number of caregiver descriptive studies have examined immunological outcomes,
      only one intervention study with caregivers of individuals with Alzheimer's
      disease, known to the authors, has included immunological outcomes. The purpose
      of this pilot study was to assess the effectiveness of a caregiver skill-building
      intervention to decrease caregiver depressive symptomatology and care-receiver
      behavioral symptoms; and to assess the feasibility and stability of the delayed
      type hypersensitivity (DTH) skin test with this population. Caregiver depressive
      symptoms decreased, while care-receiver behaviors did not. Findings suggested
      that the DTH skin test could be successfully administered to caregivers of
      individuals with Alzheimer's disease and that this skin test had short-term
      stability. There were no significant relationships between caregiver depressive
      symptoms and immune function. Study findings suggest that nurses can play a
      pivotal role in intervening with family caregivers and potentially decreasing
      their depressive symptoms.

PMID- 15152744
TI  - Effects of urinary incontinence: psychological well-being and distress in older
      community-dwelling women.
AB  - Urinary incontinence (UI) has been related to lower quality of life. However, the
      research has generally been cross-sectional, and causal relationships have not
      been determined. This research was a secondary analysis of a 6-year longitudinal
      study of chronic illness and psychological well-being in older (mean age = 73 at
      Time 1), community-dwelling women (n = 103). Over time, women with UI reported
      significantly lower subjective health, purpose in life, affect balance, personal
      growth, positive relations with others, and self-esteem and higher scores for
      depression, compared to women without UI. Incontinence had broad effects on
      multiple domains of psychological well-being that persisted over time and need to
      be addressed by clinicians.

PMID- 15152745
TI  - Atrial fibrillation and strokes: new drugs and a new attitude.

PMID- 15152746
TI  - Epidemiology and management of new-onset atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common acute or chronic cardiac disorder that can
      result in significant morbidity and mortality. Its incidence in the United States
      is increasing. Projections suggest that more than 5.6 million Americans (50% of
      whom will be > or =80 years of age) will have AF by 2050. The American College of
      Cardiology, American Heart Association, and the European Society of Cardiology
      define AF as a supraventricular tachyarrhythmia characterized by uncoordinated
      atrial activation with consequent deterioration of atrial mechanical function. On
      an electrocardiogram, AF is characterized by the replacement of P waves by rapid
      oscillations or fibrillatory waves that vary in size, shape, and timing. Evidence
      suggests that histological changes exist in the atria of patients with AF,
      however, it is not known if these changes are a cause or a consequence of AF.
      Although the fundamental mechanism underlying the disorder is not known, clinical
      identifying factors are associated with the condition. These may be divided into
      noncardiac (thyrotoxicosis, alcohol use, electrolyte imbalance, certain
      pharmacologic and recreational drugs) and cardiac causes (any cause of enlarged
      left atrium, poor ventricular function, heart surgery). The principles of
      treatment for this condition are to stabilize the patient hemodynamically,
      simultaneously determine whether a reversible cause of the AF exists, control the
      patient's heart rate, determine whether the patient should be cardioverted or
      maintained in AF, and then develop strategies to prevent the most important
      complications of stroke. This article will describe in detail the acute
      management of AF as well as its epidemiology.

PMID- 15152747
TI  - Efficacy of anticoagulation for stroke prevention and risk stratification in
      atrial fibrillation: translating trials into clinical practice.
AB  - As one of the most powerful independent risk factors for ischemic stroke and the
      most clinically relevant arrhythmia, atrial fibrillation (AF) poses a serious
      clinical and public health threat as the global population ages. AF increases the
      risk of ischemic stroke 4- to 5-fold although this statistic varies with age of
      the patient. Indeed, the prevalence rises to 1 in 25 people aged > or =60 years
      and 1 in 10 people aged > or =80 years. More than 2.3 million Americans have
      diagnosed AF, and that number is expected to increase dramatically over the
      coming decades. Ischemic stroke causes the most major disability and remains the
      third leading cause of death in the United States. Therapeutic strategies and
      optimal risk stratification offer the best hope for decreasing the burden of AF
      related thromboembolism. This article focuses on the randomized trial evidence
      for the efficacy and safety of oral vitamin K antagonists (eg, warfarin) for
      stroke prevention in AF. In particular, this article explores how well these
      findings translate into clinical practice, especially among patients with AF
      treated outside of clinical trials. Discussion centers on using evidence-based
      data to guide treatment for patients who are at increased risk for stroke. Such
      strategies would enhance the net benefit of oral anticoagulation. Concluding
      points provide information on improving risk stratification for stroke in
      patients with AF.

PMID- 15152748
TI  - Pharmacoeconomics of atrial fibrillation and stroke prevention.
AB  - Atrial fibrillation (AF) is a common arrhythmia that significantly increases the
      risk of stroke by the formation and embolism of left-atrial appendage thrombi.
      This risk can be substantially reduced with antithrombotic therapies such as
      aspirin or warfarin. Those with the highest risk receive the most benefit from
      adjusted-dose warfarin compared with aspirin or low-dose warfarin. Because of its
      efficacy in reducing strokes, adjusted-dose warfarin has been shown to be cost
      effective in several different settings, but mostly for AF patients with at least
      1 additional risk factor. Warfarin must be adjusted to international normalized
      ratios (INRs) within the target range of 2.0 to 3.0 to minimize the risk--as well
      as the cost--of stroke and bleeding. Subtherapeutic INR values occur commonly,
      but the consequences are increased risk of stroke and therefore increased costs.
      Of the several strategies available for managing anticoagulation, the key element
      to controlling costs is avoiding out-of-range values.

PMID- 15152749
TI  - Novel antithrombotic therapies for the prevention of stroke in patients with
      atrial fibrillation.
AB  - Atrial fibrillation (AF), the most common type of arrhythmia in adults, is a
      major risk factor for stroke. The prevalence of AF increases with age, occurring
      in 1% of persons <60 years of age and in almost 10% of those >80 years of age.
      Recent studies show that treatment strategies that combine control of ventricular
      rate with antithrombotic therapy are as effective as strategies aimed at
      restoring sinus rhythm. Current antithrombotic therapy regimens in patients with
      AF involve chronic anticoagulation with dose-adjusted vitamin K antagonists
      unless patients have a contraindication to these agents or are at low risk for
      stroke. Patients with AF at low risk for stroke may benefit from aspirin.
      Although vitamin K antagonists are effective, their use is problematic,
      highlighting the need for new antithrombotic strategies. This article will (a)
      provide an overview of the clinical trials that form the basis for current
      antithrombotic guidelines in patients with AF, (b) highlight the limitations of
      current antithrombotic drugs used for stroke prevention, (c) briefly review the
      pharmacology of new antithrombotic drugs under evaluation in AF, (d) describe
      ongoing trials with new antiplatelet therapies and idraparinux, and completed
      studies with ximelagatran in patients with AF, and (e) provide clinical
      perspective into the potential role of new antithrombotic drugs in AF.

PMID- 15152750
TI  - In the firing line: the nurse academic in practice.

PMID- 15152751
TI  - Introducing an early warning scoring system in a district general hospital.
AB  - One of the critical care outreach service's aims in this local hospital was to
      develop an assessment tool to help identify patients in danger of deterioration.
      This paper describes the introduction of an early warning scoring system between
      April 2001 and March 2002 to the surgical unit of a district general hospital.
      The informal and gradual approach used to optimize the effectiveness of
      introducing the early warning scoring system is highlighted. Explanations are
      given of the training processes undertaken, the pilot evaluation and lessons
      learned from the process. Using the experiences of the outreach service in
      introducing the early warning scoring system, this paper aims to provide thought
      for others considering a similar initiative in their area

PMID- 15152752
TI  - Can nurses in cardiology areas prepare patients for implantable cardioverter
      defibrillator implant and life at home?
AB  - This study explored nurses' confidence and competence in preparing patients for
      having an implantable cardioverter defibrillator implanted and for life at home
      after discharge. Whilst research has identified various physical and psychosocial
      effects to patients and their partners associated with device implant and
      subsequent lifestyle adjustments, no research has explored nurses' knowledge of
      the device or these effects. A survey was designed using a purposive sample of
      152 nurses from cardiology areas in four large teaching hospitals and a 28-point
      postal questionnaire to explore knowledge of the device and its impact. Most
      subjects were not confident in their abilities to prepare patients for implant or
      life at home after implant. Knowledge of the device and its effects appeared
      poorly understood by all nurses, irrespective of additional qualifications,
      length of time since qualifying or area of work. Many participants were aware of
      the poor knowledge level of nurses and identified it as a weakness in current
      care practices. Lack of understanding may impair preparation of patients for
      implantation of or for living with an implantable cardioverter defibrillator, and
      feasible strategies to change this situation will require careful consideration
      and further investment.

PMID- 15152753
TI  - 'Do not attempt resuscitation' decision-making: a study exploring the attitudes
      and experiences of nurses.
AB  - At the time of the research being undertaken, a policy regarding resuscitation
      decisions did not exist at a local hospital. However, it was proposed that a new
      'do not attempt resuscitation' policy should be implemented. Nurses' attitudes
      to, and experiences of, the communication involved in 'do not attempt
      resuscitation' decision-making were explored and compared with five variables
      (nurses' age, nurses' grade, years of nursing, area of nursing practice and
      length of nursing experience on current ward). Seventy-eight qualified nurses,
      who made up a convenience sample, participated in the study. An adapted
      questionnaire was used to explore nurses' attitudes to, and experiences of, 'do
      not attempt resuscitation' decision-making. The findings suggested that nurses'
      attitudes did generally concur with the guidelines outlined in the new policy.
      However, in practice, there were many disparities between nurses' experiences of
      current 'do not attempt resuscitation' decision-making and the policy's
      guidelines. There were no significant differences between nurses' attitudes to
      current 'do not attempt resuscitation' decision-making and the five variables.
      However, there was one significant difference identified between nurses'
      experiences and the area of nursing practice (p=0.008). To adhere to the
      principles of the forthcoming 'do not attempt resuscitation' policy at the local
      hospital, the research findings have suggested that changes need to occur to both
      nurses' attitudes to and nurses' experiences of current 'do not attempt
      resuscitation' decision-making.

PMID- 15152754
TI  - Gastric tonometry and monitoring gastrointestinal perfusion: using research to
      support nursing practice.
AB  - The principles and physiological underpinnings of gastric tonometry are reviewed.
      Tonometric variables, including the PtCO2, pHi and CO2 gap, are described and
      critiqued as measurements of gastrointestinal perfusion. Increases in
      gastrointestinal CO2 unrelated to gastrointestinal hypoperfusion are discussed
      within different clinical contexts. The technical limitations of gastric
      tonometry, including procedural errors and PtCO2 measurement are discussed in
      relation to the accuracy of tonometric measurements. Tonometric measurement using
      semi-continuous air tonometry is introduced as a strategy to minimize technical
      limitations.

PMID- 15152756
TI  - [Contact eczema requires detective talent].

PMID- 15152755
TI  - Intensive care nurses' experiences of assessing and dealing with patients'
      psychological needs.
AB  - Several authors have highlighted the short- and long-term psychological effects
      of an intensive care unit (ICU) stay. Few authors have discussed the nurses'
      perceptions of psychological care. In this research, 12 nurses, who currently
      work in ICU, were interviewed using a semi-structured technique. Six categories
      were developed about issues in psychological care. Implications for practice
      included the important role of the family, need for improved communication and
      improved staff awareness of issues.

PMID- 15152757
TI  - [COPD diagnosis in the practice. Can the peak-flow-meter replace spirometry?].

PMID- 15152758
TI  - [Vaccination deduction. The consultation fee concerns every case].

PMID- 15152759
TI  - [Fatal bleeding under warfarin plus cranberry juice. Is it due to salicylic
      acid?].

PMID- 15152760
TI  - [Capsule endoscopy: painfree in the depths of the small intestine].

PMID- 15152761
TI  - [Women's hearts beat differently. Every second infarct without chest pain].

PMID- 15152762
TI  - [Medical school and homeopathic measures. What helps in climacteric?].

PMID- 15152763
TI  - [Bleeding diverticulum. Photo proof in emergency colonoscopy].

PMID- 15152764
TI  - [Nutrition during pregnancy--current aspects].
AB  - A balanced diet that provides an adequate supply of vitamins and minerals is
      essential for normal fetal development. Maternal morbidity is also lower, since
      such complications of pregnancy as preeclampsia and premature birth occur less
      frequently. Consideration should be given to folate deficiency--in particular
      during the periconceptive period--and iron deficiency during pregnancy. For the
      structural development of the fetus, long-chain polyunsaturated fatty acids also
      appear to have a major role to play. Daily iodine supplementation should be used
      to avoid goiter in mother and child. Calcium appears to have a protective effect
      against preeclampsia and hypertension, as also do vitamins E and C. The tocolytic
      action of magnesium can help reduce the incidence of premature birth. Such noxae
      as alcohol and nicotine should be avoided completely during the entire pregnancy.

PMID- 15152765
TI  - [Drug therapy in pregnancy--a practical guide].
AB  - Pharmacotherapy in pregnancy is often problematic, since both the mother-to-be
      and her doctor are often concerned about possible risks for the unborn child. On
      the other hand, we now have sufficient knowledge of a whole range of medications,
      to enable the recommendation of safe drug treatment in almost any clinical
      situation. The family doctor, too, is often consulted by pregnant women requiring
      treatment for internistic problems. These include such pregnancy-unrelated
      problems as essential hypertension or bronchial asthma, as well as pregnancy
      related disorders such as urinary tract infection or gastrointestinal problems.

PMID- 15152766
TI  - [Infections in pregnancy].
AB  - Infections of the mother-to-be continue to be a problem for a successful birth.
      However, on the basis of the case history, special examination methods (infection
      serology, pathogen determination) and the noninvasive and invasive prenatal
      diagnostic work-up, the risks for the fetus can be much better assessed than 10
      15 years ago. This avoids unnecessary terminations of the pregnancy, better
      counseling of the parents-to-be, appropriate monitoring of the fetus, and
      improved treatment of mother and child during the pregnancy, or of the neonate.
      To ensure optimal care of mother and fetus, the family doctor, too, should be
      familiar with the major relevant infections, their symptoms, prophylactic options
      and treatment. As a general rule, cooperation with midwives, obstetricians and/or
      obstetric centers, specialist laboratories and neonatologists is essential.

PMID- 15152767
TI  - [Treating high blood pressure in acute stroke].

PMID- 15152768
TI  - [EBM plans attend to unrest. Up to 50,000 Euro less fees yearly].

PMID- 15152769
TI  - [Since Ash Wednesday: State commissar rules the colleagues].

PMID- 15152770
TI  - [Stubborn reflux pain, inconspicuous esophagus. Which therapy brings the fastest
      relief?].

PMID- 15152771
TI  - [Graded therapy in reflux disease. "In severe cases 40 mg., in milder 20 mg."].

PMID- 15152773
TI  - [Hepatic encephalopathy. Mostly treatable -- rarely detected].

PMID- 15152772
TI  - [Pharmacies offer free nutrition seminars. To live lighter in Germany].

PMID- 15152774
TI  - [Since blood sugar is better controlled. Well informed diabetics live longer].

PMID- 15152775
TI  - [Equally whether the child's lung or chronically inflamed bronchi. Acute
      bacterial infections have to be terminated fast].

PMID- 15152776
TI  - [Severe fatigue in cancer. Causes from A as anemia to Z as cytostatics].

PMID- 15152777
TI  - [Beta blocker activates release of NO. Radical against atherosclerosis].

PMID- 15152778
TI  - [Desensitization for those afflicted with hay fever. With 4 pricks hyposensitized
      to pollen].

PMID- 15152779
TI  - [Heart failure. Diagnosis and prognosis readable from a simple blood test].

PMID- 15152780
TI  - [Osteoporosis].

PMID- 15152781
TI  - [In the jungle of psychology specialties. Who is duly qualified?].

PMID- 15152782
TI  - [Paul Ehrlich was born 150 years ago. The benefactor of Humanity].

PMID- 15152783
TI  - Suicide note themes and suicide prevention.
AB  - OBJECTIVE: The aim was to determine if suicide note themes might inform suicide
      prevention strategies. METHOD: The themes of 42 suicide notes from the Northern
      Ireland Suicide Study (major psychological autopsy study) were examined. RESULTS:
      The commonest themes were "apology/shame" (74%), "love for those left behind"
      (60%), "life too much to bear" (48%), "instructions regarding practical affairs
      post-mortem" (36%), "hopelessness/nothing to live for" (21%) and "advice for
      those left behind" (21%). Notes of suicides with major unipolar depression were
      more likely than notes of suicides without major unipolar depression to contain
      the themes "instructions regarding practical affairs post-mortem" (67% versus
      19%, p = 0.005) and "hopelessness/nothing to live for" (40% versus 11%, p =
      0.049). Notes of suicides with a previous history of deliberate self-harm were
      less likely than notes of suicides without a history of deliberate self-harm to
      contain the theme "apology/shame" (58% versus 87%, p = 0.04). Notes of elderly
      suicides were more likely than non-elderly notes to contain the theme "burden to
      others" (40% versus 3%, p = 0.03). CONCLUSIONS: The fact that three quarters of
      suicide notes contained the theme "apology/shame" suggests that the deceased may
      have welcomed alternative solutions for their predicaments. Scrutiny of suicide
      note themes in the light of previous research findings suggests that cognitive
      therapy techniques, especially problem solving, may have an important role to
      play in suicide prevention and that potential major unipolar depressive (possibly
      less impulsive) suicides, in particular, may provide fertile ground for
      therapeutic intervention (physical and psychological). Ideally all primary care
      doctors and mental health professionals working with (potentially) suicidal
      people should be familiar with basic cognitive therapy techniques, especially
      problem solving skills training.

PMID- 15152784
TI  - Screening for depression in a geriatric rehabilitation sample.
AB  - OBJECTIVE: To examine the utility of a short depression inventory (SDI) for use
      with elderly medical inpatients. METHOD: Subjects were 132 consecutive admissions
      to the inpatient geriatric rehabilitation unit at MetroHealth Medical Center, a
      general medical teaching hospital in Cleveland, Ohio. Sixty of the original
      sample qualified for inclusion in the final sample. Within the first five days of
      admission, all subjects were administered the Mini-Mental Status Examination
      (MMSE). Ss who scored 20 or above were asked to complete the SDI and the GDI. A
      clinical interview used DSM-III-R criteria to establish the diagnosis of major
      depression. The order of presentation of questionnaire or interview was varied to
      control for the effects of presentation order. RESULTS: When an optimal cut-off
      score of 4 or above on the SDI was used, the sensitivity and specificity were
      100% and 85% respectively. Using the GDS, sensitivity and specificity were 100%
      and 90%. CONCLUSIONS: Using the SDI, impressive sensitivity and specificity were
      achieved. The SDI was also essentially equivalent to the GDI psychometrically.
      The SDI appears to have good promise as a depression screen in medical
      populations.

PMID- 15152785
TI  - Defense mechanisms in a community-based sample of female adolescents with partial
      eating disorders.
AB  - OBJECTIVES: The purpose of this study is to assess whether female adolescents
      diagnosed with partial eating disorders (EDs) will show less adaptive defense
      mechanisms compared to female controls with no-ED. METHODS: The following
      questionnaires were administered to 423 female high-school students: The Eating
      Attitudes Test (EAT-26), the Defense Style Questionnaire (DSQ), and Life Style
      Index (LSI) (both tapping defense mechanisms), and a structured questionnaire
      assessing eating-related issues. Weight and height were also recorded. Partial
      anorexia nervosa (AN) and bulimia nervosa (BN) were defined with the combination
      of a maladaptive EAT score and fulfillment of adapted DSM-IV criteria. RESULTS:
      Compared to non-ED controls, participants with partial AN and partial BN used
      more immature defenses, including the DSQ-immature defense style (only those with
      partial BN) and LSI-regression, as well as more neurotic defenses, namely the DSQ
      neurotic defense style, and LSI-compensation and displacement. CONCLUSIONS: The
      combined use of immature and neurotic defenses may be associated with a greater
      risk to develop a partial ED in adolescent females.

PMID- 15152786
TI  - Religion, race, and breast cancer survival.
AB  - OBJECTIVE: The study investigated whether any of four measures of religiousness
      predicted longer survival for 145 African-American and 177 White women diagnosed
      with breast cancer in Connecticut between January 1987 and March 1989. METHOD:
      Multivariate Cox proportional hazards models included a religious predictor and
      sociodemographic, biomedical, treatment, behavioral, and medical care
      covariables. RESULTS: The no denomination group had a hazard ratio (HR) of 4.39
      (95% Confidence Interval (CI) = 1.42, 13.64). Other measures of religiousness did
      not yield statistically significant results but showed a consistent pattern of
      nonreligiousness being more strongly and negatively related to breast cancer
      survival in African Americans than in Whites. CONCLUSIONS: Exploratory models
      confirmed that lack of religiousness was associated in this sample with poor
      breast cancer survival among African American women.

PMID- 15152787
TI  - Religious attendance and continuity of care.
AB  - OBJECTIVE: The purpose of this study was to determine whether a relationship
      exists between religious attendance and continuity of care. METHODS: We
      investigated this relationship in a large national database--the National Health
      and Nutrition Examination Survey III--which contains information on religious
      attendance, continuity of care, and potential confounders that might mediate the
      relationship such as health status and socioeconomic status. RESULTS: A total of
      18,162 participants 17 years of age or older were included in the analysis.
      People who attended religious services were more likely to have continuity with a
      provider than people who did not attend such services (65% vs. 35%, p < .001).
      This association persisted after controlling for demographic, socioeconomic, and
      health status variables using regression analysis. CONCLUSION: This study
      documents a significant association between attendance at religious services and
      continuity with a usual provider. Continuity with a regular medical provider may
      influence the association of religious attendance and health outcomes.

PMID- 15152788
TI  - Treatment of perinatal delusional disorder: a case report.
AB  - This article is a report on a complicated case of delusional disorder in
      pregnancy and lactation, and effective multidisciplinary treatment. Few reports
      in the literature concern delusional disorder in pregnancy, or regard
      olanzapine's safety in pregnancy and lactation. A gravid woman in her third
      trimester merited twin diagnoses of delusional disorder and borderline
      personality disorder, and was successfully treated with olanzapine and
      psychotherapy during pregnancy and lactation. Her infant was large for
      gestational age (LGA) and had Erb's palsy, which resolved, and remained healthy
      at six months, with continued breastfeeding. Her delusional beliefs did not
      recur, nor did she have postpartum depression or psychosis.

PMID- 15152789
TI  - Galantamine in the treatment of adult autism: a report of three clinical cases.
AB  - OBJECTIVE: To study the usefulness of galantamine, a competitive, reversible
      acetylcholinesterase inhibitor (AChEI), in adults diagnosed with autism (in
      accordance with DSM-IV-TR Axis I clinical criteria) before age three years.
      METHODS: To promote verbalization and meaningful speech sound production through
      biochemical enhancement of the serotonergic subsystem of the central nervous
      system (CNS), galantamine 4 mg qhs was administered, with indicated dose
      increases. RESULTS: Verbal fluency increased in all patients, according to their
      caregivers. One patient developed a macular rash that abated when the medication
      was discontinued. After one month on donepezil 5 mg qhs, verbal and behavioral
      regression again led to discontinuation. Doses for the other patients have been
      escalated by 4 mg daily each month to a maximum of 12 mg, with improvement
      following each increase. CONCLUSIONS: Cholinergic stimulation of the CNS
      serotonergic subsystem with galantamine may enhance expressive language and
      communication in autistic adults. Clinical trials are needed to study adjuvant
      therapy with galantamine in such patients.

PMID- 15152790
TI  - Severe cardiovascular side effects of olanzapine in an elderly patient: case
      report.
AB  - Olanzapine, an atypical antipsychotic, is often regarded as a safe choice for
      psychosis management. We hereby report an aged case that presented with conscious
      depression, bradycardia, hypotension, miosis and hypothermia. Olanzapine was
      thought to be the offending agent. His condition improved with supportive
      therapy.

PMID- 15152791
TI  - High-dose olanzapine-induced improvement of preexisting type 2 diabetes mellitus
      in schizophrenic patients.
AB  - OBJECTIVE: During the last few years there have been numerous publications
      concerning glucose dysregulation and antipsychotic treatment with new-onset
      diabetes and exacerbation of existing disease being reported. At the same time
      three anecdotal reports describing decrease of blood glucose level during
      clozapine and olanzapine treatment were published. Here we report two cases of
      clinically significant dose-related reductions in glucose levels in schizophrenic
      and schizoaffective patients suffering from pre-existing type 2 diabetes during
      high dose (40 mg/day) olanzapine treatment. To the best of our knowledge, this is
      a first report of decreasing glucose blood levels in association with olanzapine
      therapy in pre-existing type 2 diabetes. Antipsychotic treatment with high doses
      of olanzapine showed that the relationship between olanzapine and glucose
      regulation is more unambiguous than usually assumed. CONCLUSIONS: There is a need
      for further studies in order to define the influence of high dose olanzapine for
      schizophrenic and schizoaffective patients suffering from type 2 diabetes.

PMID- 15152792
TI  - Munchausen Syndrome by Proxy: two case reports and an update of the literature.
AB  - OBJECTIVES AND METHODS: Munchausen Syndrome by Proxy (MSP) may significantly
      hamper the normal development of children. Our aim was to describe the first two
      Israeli children who fit this diagnosis. RESULTS: Case #1 was diagnosed at the
      age of seven months with failure to thrive, severe recurrent vomiting, and
      recurrent unexplained fever. Medical tests performed were normal. No improvement
      was noted following prolonged treatment, which included several surgical
      interventions. Case #2 was hospitalized at the age of four years because of
      recurrent convulsive episodes. Medical examinations performed were normal, and
      there was no improvement in the reported seizure disorder despite continuous
      treatment. In both cases, MSP was suspected because of a persistent illness that
      could not be explained by adequate medical basis, and because the symptoms and
      signs occurred only in the mother's presence. A confrontation was made, leading
      to rapid deterioration of the hitherto devoted relationship of the mother of case
      #1 with her child, and of the previous cooperative relationship of both mothers
      with the medical staff. Removal of both children from their families ensued, with
      considerable improvement within a brief period, which continued in a one- to two
      year follow-up period. CONCLUSIONS: The study reviews the required diagnostic
      criteria for MSP and possible treatment options.

PMID- 15152793
TI  - From desegregation to diversity: how far have we really come?

PMID- 15152794
TI  - Disability as difference and the nursing profession.
AB  - Disability viewed as human difference under the broad umbrella of cultural
      diversity provides new possibilities for nursing to unite and show what it
      believes and stands for as a profession. Core essentials of professional nurses
      are considered. As nurse educators challenge traditions that perpetuate barriers
      to valuing human differences, the profession, those accepted into it, and those
      served by it will benefit.

PMID- 15152795
TI  - Valuing differences among nursing students.
AB  - Across the United States, discussions and decisions are occurring in schools of
      nursing as nurse educators attempt to comply with the Americans with Disabilities
      Act. This article examines the ethos behind these decisions and the Act. The old
      paradigm of tolerating differences among people and students with disabilities is
      contrasted with the emerging paradigm of valuing these differences. The author
      supports the viewpoint that people with disabilities should be welcomed, even
      recruited, into nursing.

PMID- 15152796
TI  - Educating nursing students with disabilities: one nurse educator's journey from
      questions to clarity.
AB  - Nurse educators are increasingly facing accommodation of students with
      disabilities in their nursing curricula, and questions regarding issues of
      fairness to all students and patient safety often rise. Several schools and state
      boards of nursing have turned to writing lists of essential functions of nursing
      to provide a framework. Before the list is written, educators need to examine
      their own thoughts on the definition of nursing and the abilities essential to
      functioning as a nurse.

PMID- 15152797
TI  - Inclusion of people with physical disabilities in nursing education.
AB  - This article proposes that qualified individuals with physical disabilities can
      and should be included in nursing education. When nursing is viewed as a
      humanistic profession, involving caring relationships grounded in nursing
      knowledge, it is clear that people with disabilities are capable of fulfilling
      the goals of the nursing profession. Reasonable accommodation and creative access
      are discussed as means to facilitate inclusion. Potential concerns of nurse
      educators are addressed, with emphasis on the erroneous assumption that people
      with disabilities will be unable to provide safe care. The many benefits of
      including people with physical disabilities into the nursing profession are
      highlighted, and the importance of nurse educators in facilitating this process
      is explored.

PMID- 15152798
TI  - Nursing faculty members' perceptions, knowledge, and concerns about students with
      disabilities.
AB  - This study surveyed nursing program faculty about their perceptions, knowledge,
      and concerns regarding nursing students with disabilities. Surveys were completed
      by 88 faculty members in eight programs. Faculty members rated the extent to
      which they perceived that individuals with different types of disabilities had
      the ability to be nursing students and professionals; their level of knowledge
      about how to teach and accommodate students with disabilities; and their level of
      concern regarding nursing students with disabilities. On a scale from 1 (strong
      agreement) to 6 (strong disagreement), faculty members' mean ratings of the
      ability of individuals with disabilities to be successful nursing students and
      professionals, were 3.2 and 3.4, respectively. On a scale from 1 (low) to 6
      (high), faculty members' mean ratings of their knowledge and concerns related to
      students with disabilities were 2.7 and 4.0, respectively. These results suggest
      nursing faculty need training regarding nursing students with disabilities.

PMID- 15152800
TI  - Gender-based barriers for male students in nursing education programs: prevalence
      and perceived importance.
AB  - To meet the recent call to increase the number of nurses by recruiting men,
      nursing education programs will need to reduce gender-based barriers. No study
      found has adequately quantified the prevalence and perceived importance of
      barriers to men in nursing education programs. These barriers create an academic
      environment that is unfriendly to men. As such, I defined a new construct, "male
      friendliness," as a function of the presence and importance of these barriers.
      The aims of this study were to describe the prevalence and perceived importance
      of barriers and to develop a tool to measure male friendliness in nursing
      programs. A pilot tool addressing 33 barriers, which were obtained from the
      literature, my experience, and a panel of nurse educators, was mailed to 200 male
      nurses. The findings revealed that seven barriers were importantly different in
      prevalence between different subsamples of male nurses, and no barrier was rated
      unimportant by more than 20% of respondents. The similarities in findings between
      groups of male nurses, diverse in geography, school attendance, and graduation
      dates, suggest that the barriers men face in nursing school are pervasive,
      consistent, and have changed little over time. From the findings, the Inventory
      of Male Friendliness in Nursing Programs (IMFNP) was developed.

PMID- 15152799
TI  - Application of the caring curriculum to education of Hispanic/Latino and American
      Indian nursing students.
AB  - To increase work force diversity and decrease health disparities, students of
      color must be successful in nursing programs. Unfortunately, the literature
      describes numerous barriers to these students' success, originating in both the
      socioeconomic and cultural environment in which they live and work, and in
      schools of nursing. In this study, seven filmed interviews of Hispanic/Latino and
      American Indian nurses were examined for barriers to educational success.
      Eighteen barriers to success were identified, examples of these barriers were
      extracted from the data, and the caring curriculum was proposed as one possible
      solution for removing or mitigating these barriers. Principles of the caring
      curriculum were then used to provide a framework for suggested retention
      strategies for Hispanic/Latino and American Indian nursing students.

PMID- 15152801
TI  - Native American learning: an integrative model.
AB  - Cultural variations influence health care needs of individuals in various
      cultural groups. Oral tradition, dreams, and spirituality are important in the
      lives of many Native Americans. There are few Native American nurses, so health
      care is often provided to members of this group by nurses who have different
      cultural backgrounds and who may not understand pertinent history and cultural
      practices. This article describes the planning for and teaching of a class for
      undergraduate and graduate health care students to increase understanding of the
      unique health care needs of Native Americans. The structure of the class included
      both classroom and clinical hours. Essential components involved study and
      analysis of the historical events, cultural issues, and current health care needs
      and services of Native Americans. Approaches that can be applied to plan courses
      to explore health care needs of various cultures are presented.

PMID- 15152802
TI  - Pladienolides, new substances from culture of Streptomyces platensis Mer-11107.
      I. Taxonomy, fermentation, isolation and screening.
AB  - Seven new macrolides having a 12-membered ring, which we termed pladienolides,
      were isolated from the fermentation broth of Streptomyces platensis Mer-11107.
      Six of the seven pladienolides inhibited hypoxia-induced reporter gene expression
      controlled by human VEGF promoter with IC50 values of 0.0018-2.89 microM. They
      also demonstrated growth-inhibitory activity against U251 human glioma cells in
      vitro. Pladienolides are highly potent inhibitors of both hypoxia signals and
      cancer cell proliferation, and thus may be useful as antitumor agents.

PMID- 15152803
TI  - Pladienolides, new substances from culture of Streptomyces platensis Mer-11107.
      II. Physico-chemical properties and structure elucidation.
AB  - In the course of our screening using fermented broth from soil microorganisms,
      novel metabolites (pladienolides), possessing inhibitory activity against
      vascular endothelial growth factor (VEGF) expression and cancer cell
      proliferation, were isolated from Streptomyces platensis Mer-11107. Pladienolides
      A (1), B (2), C (3), D (4), E (5), F (6), and G (7) were found to be novel 12
      membered macrolides by spectroscopic studies including 1H, 13C NMR, HMQC, HMBC,
      and NOE experiments. Pladienolides are unusual 12-membered macrolides having a
      long side chain at the carbon that bears a lactone oxygen.

PMID- 15152804
TI  - Pladienolides, new substances from culture of Streptomyces platensis Mer-11107.
      III. In vitro and in vivo antitumor activities.
AB  - We have discovered seven novel 12-membered macrolides, pladienolides A to G, from
      Streptomyces platensis Mer-11107, with pladienolide B the most potently
      inhibiting hypoxia induced-VEGF expression and proliferation of the U251 cancer
      cell line. A growth inhibitory study using a 39-cell line drug-screening panel
      demonstrated that pladienolide B has strong antitumor activities in vitro. A
      COMPARE analysis reveals that it has a unique antitumor spectrum that sets it
      apart from anticancer drugs currently in clinical use. This result suggests that
      pladienolide B has a novel mechanism of action. A series of xenograft studies
      were conducted to evaluate the in vivo potency of pladienolides. Pladienolide B
      extensively inhibited tumor growth in xenograft models. In the most sensitive
      model, using BSY-1 xenografts, tumors were completely regressed by administration
      of pladienolide B. For the reason of their novel mechanism of action and
      excellent in vivo efficacy, pladienolides appear to have major potential for use
      in cancer treatment.

PMID- 15152806
TI  - New aminocoumarin antibiotics from a cloQ-defective mutant of the clorobiocin
      producer Streptomyces roseochromogenes DS12.976.
AB  - Three new antibiotics, vanillobiocin, isovanillobiocin and declovanillobiocin,
      were isolated from the culture broth of a cloQ-defective mutant of the
      clorobiocin producer Streptomyces roseochromogenes, which is blocked in the
      biosynthesis of the prenylated 4-hydroxybenzoic acid moiety of clorobiocin.
      Spectroscopic analysis showed that the isolated compounds were similar to
      clorobiocin, but contained vanillic acid as the acyl component instead of the
      prenylated 4-hydroxybenzoic acid present in clorobiocin. Isovanillobiocin differs
      from vanillobiocin by the position of the pyrrole unit attached to the sugar
      moiety of the antibiotic. Declovanillobiocin lacks the chlorine atom at the
      aminocoumarin ring. All three compounds had lower antibiotic activity against
      Bacillus subtilis than clorobiocin.

PMID- 15152805
TI  - CE-108, a new macrolide tetraene antibiotic.
AB  - In the search for strains producing antifungal compounds, a new tetraene
      macrolide CE-108 (3) has been isolated from culture broth of Streptomyces
      diastaticus 108. In addition, the strain also produces the previously described
      tetraene rimocidin (1) and also the aromatic polyketide oxytetracycline. Both
      tetraene compounds, structurally related, are produced in a ratio between 25 to
      35% (CE-108 compared to rimocidin), although it can be inverted toward CE-108
      production by changing the composition of the fermentation medium. This paper
      deals with the characterization of the producer strain, fermentation,
      purification, structure determination and biological properties of the new
      macrolide tetraene CE-108.

PMID- 15152807
TI  - Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. I. Taxonomy,
      isolation and characterization.
AB  - GE 23077 factors A1, A2, B1 and B2 are novel antibiotics isolated from
      fermentation broths of an Actinomadura sp. strain. GE23077 antibiotics are cyclic
      peptides, which inhibit Escherichia coli RNA polymerase at nM concentrations.
      Both rifampicin-sensitive and rifampicin-resistant polymerases are inhibited,
      whereas E. coli DNA polymerase and wheat germ RNA polymerase are substantially
      not affected. In spite of the potent activity on the enzyme, the antibiotics
      generally show poor activity against whole cell bacteria. The spectrum of
      activity is restricted to Moraxella catarrhalis, including clinical isolates,
      with partial activity against Neisseria gonorrhoeae and Mycobacterium smegmatis.

PMID- 15152809
TI  - API-mass spectrometry of polyketides. I. A study on the fragmentation of
      triketide lactones.
AB  - The fragmentation of delta-lactones, particularly triketide lactones, has been
      studied to provide information on the behavior of polyketides under atmospheric
      pressure ionization mass spectrometry (API-MS). The principal fragmentation
      patterns of triketide lactones are characterized by two sequential dehydrations
      followed by loss of CO to give hydrocarbon fragments. A particular goal of this
      study was an understanding of the origins of the two water molecules from the
      dehydrations. 18O- and 2H-isotope labeling experiments with delta-valerolactone
      suggest a mechanism for lactone fragmentation in which ionization by proton
      transfer is followed by rapid equilibration of ring-opened and ring-closed forms,
      which results in exchange of the ionizing proton into the hydrocarbon framework
      of the compound and randomization of the oxygens of the lactone. Subsequent
      fragmentation primarily involves sequential loss of water and CO. Similar
      experiments with the more complex triketide lactones show that their mass spectra
      share common features with that of delta-valerolactone, together with an
      additional water loss from the 3-hydroxyl group.

PMID- 15152808
TI  - Structures of grixazone A and B, A-factor-dependent yellow pigments produced
      under phosphate depletion by Streptomyces griseus.
AB  - A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) acts as a
      microbial hormone that induces morphological development and secondary metabolism
      in Streptomyces griseus. A diffusible yellow pigment is produced by S. griseus in
      an A-factor-dependent manner under phosphate depletion. Detailed analysis of the
      pigment production by S. griseus cultivated in minimal liquid medium containing
      different concentrations of phosphate showed that the pigment was actively
      produced in the presence of low concentrations of phosphate and the production of
      the pigment was completely repressed in the presence of 2.5 mM KH2PO4. HPLC
      analysis of the culture supernatant showed that the pigment consisted of two
      major, structurally related compounds and they were produced at different ratios
      depending on the concentration of phosphate in the medium. The structures of the
      two major compounds, designated as grixazone A and B, were determined by
      spectroscopic analyses as 1-[[2-(acetylamino)-2-carboxyethyl]thio]-2-amino-3-oxo
      8-formyl-3H-phenoxiazine and 1-[[2-(acetylamino)-2-carboxyethyl]thio]-2-amino-3
      oxo-8-carboxyl-3H-phenoxiazine, respectively. Grixazone A was a novel compound,
      although grixazone B was reported in a patent as a parasiticide produced by
      Streptomyces sp. DSM3813.

PMID- 15152810
TI  - PP2A inhibitors, harzianic acid and related compounds produced by fungus strain F
      1531.

PMID- 15152811
TI  - The influence of enamel matrix derivative associated with insulin-like growth
      factor-I on periodontal ligament fibroblasts.
AB  - BACKGROUND: Enamel matrix derivative (EMD) has recently been shown to promote
      periodontal regeneration in vivo. Insulin-like growth factor-I (IGF-I) is a
      potent modulator of periodontal regeneration stimulating cell proliferation,
      differentiation, synthesis of type I collagen, and non-collagenous proteins.
      However, the biochemical effects of these factors on periodontal ligament (PDL)
      fibroblasts are not completely understood. The objective of the present study was
      to evaluate the effect of EMD, IGF-I, and the combination of these two factors on
      the proliferation, adhesion, migration, and expression of type I collagen in PDL
      fibroblasts. METHODS: The proliferation rate was measured by automated cell
      counting and immunohistochemical expression of proliferating cell nuclear antigen
      (PCNA). The cell adhesion was analyzed by a colorimetric assay and cell migration
      was measured in Boyden chambers. Type I collagen expression and production was
      determined by semi-quantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS:
      The results indicated that the proliferation of PDL fibroblasts was significantly
      stimulated by EMD and EMD plus IGF-I in a dose- and time-dependent manner. EMD,
      IGF-I, and the combination of both factors had no effects on cellular migration
      and adhesion or expression and production of type I collagen. CONCLUSION: Our
      results showed that EMD, IGF-I, and the combination of both factors stimulated
      PDL fibroblast proliferation, whereas these factors did not affect adhesion,
      migration, or expression of type I collagen of these cells.

PMID- 15152812
TI  - Periodontitis and coronary artery calcification: the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - BACKGROUND: Periodontitis has been linked to coronary heart disease (CHD) risk,
      possibly through providing a systemic inflammatory burden. Few studies have
      evaluated periodontitis and subclinical measures of atherosclerosis. Coronary
      artery calcification (CAC) is an emerging marker for atherosclerosis, and past
      studies suggest that it predicts incident CHD in asymptomatic populations.
      METHODS: In 1996-1998, dental examinations were performed on 6,931 participants
      in the Atherosclerosis Risk in Communities (ARIC) cohort. Extent of periodontitis
      was measured by the percent of sites with attachment level (AL) > or = 3 mm. In
      1999-2000, CAC was measured by cardiac gated mechanical or helical computed
      tomography in 269 dental examinees and edentulous subjects from the Minnesota and
      North Carolina field centers of ARIC who were free of clinically recognized CHD.
      A traditional Agatston score for CAC was calculated. RESULTS: Compared to
      subjects with no or mild periodontitis (<10% of sites with AL > or = 3 mm),
      subjects with moderate or severe periodontitis (> or = 10% of sites with AL > or
      = 3 mm) were more likely to have CAC > or = 100, but this difference was not
      statistically significant (odds ratio [OR]: 1.78; 95% confidence interval [CI]:
      0.65 to 4.86). This association was partially but not completely attenuated when
      adjusted for demographic factors and traditional CHD risk factors (OR: 1.51; 95%
      CI: 0.54 to 4.23). CONCLUSIONS: These results suggest that periodontitis is not
      strongly associated with CAC. This study offers some reference for the magnitude
      of the association between CAC and periodontitis and information regarding the
      minimal power necessary for future studies.

PMID- 15152813
TI  - The prevalence of surgical complications of the sinus graft procedure and their
      impact on implant survival.
AB  - BACKGROUND: Grafting of the maxillary sinus floor has been performed successfully
      over the last decade. The ultimate goal of this procedure is to allow surviving
      implants to support a functional prosthesis. Surgical complications of the
      procedure are rarely reported and their impact on implant survival has been
      investigated even to a lesser extent. The purpose of this study was to evaluate
      the prevalence of surgical complications of the sinus graft procedure and their
      impact on implant survival. METHODS: The study consisted of 70 patients who
      underwent 81 sinus graft procedures using the lateral wall approach from 1995 to
      2000. A total of 212 screw-shaped implants were placed in the grafted sinuses and
      were restored by fixed prosthesis. Mean follow-up period for the implants was
      43.6 months. Intra- and postoperative complications were thoroughly documented
      regarding clinical signs, times of occurrence, and treatment regimens. RESULTS:
      Perforation of the Schneiderian membrane was the major intraoperative
      complication, observed in 36 of the 81 sinuses (44%). Of the 70 patients, seven
      (10%) suffered from postoperative complications, specifically related to the
      sinus graft procedure, which included an uncommon cyst formation and an
      infection. Membrane perforations were strongly associated with the appearance of
      postoperative complications (specific and non-specific to the procedure) (P <
      0.001). However, no association was found between membrane perforations or
      postoperative complications and implant survival. CONCLUSIONS: Intraoperative
      complications may lead to postoperative complications. Surgical complications did
      not significantly influence implant survival.

PMID- 15152814
TI  - Association of Fcgamma receptor IIa genotype with chronic periodontitis in
      Caucasians.
AB  - BACKGROUND: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors IIIa
      and IIIb (FcgammaRIIIa and FcgammaRIIIb) have been shown as risk factors for
      periodontitis. The aim of this study is to examine whether FcgammaRIIa
      polymorphism is associated with a disease risk as well. METHODS: Baseline
      periodontal and general health examinations were carried out on 1,221 Caucasian
      adults. From these, 422 subjects with moderate to severe, or little or no
      periodontal disease were assigned to two groups according to their mean clinical
      attachment loss (CAL). Subjects with mean CAL > or = 2.94 mm were diagnosed with
      chronic periodontitis (n = 213, 62 never-smokers and 151 smokers). Subjects with
      mean CAL < or = 1.77 mm were considered as having little or no periodontal
      disease and designated as controls (n = 209, 125 never-smokers and 84 smokers).
      The FcgammaRIIa genotype for three bi-allelic polymorphisms (FcgammaRIIa-R/ R131,
      R/H131, and H/H131) was determined by means of allele-specific polymerase chain
      reactions. RESULTS: The distribution of FcgammaRIIa genotype between the patient
      and control groups was significantly different, with enrichment of the high
      ligand-binding genotype FcgammaRIIa-H/H131 in the patients (patients versus
      controls: 36.6% versus 25.4%; P = 0.04). Multivariate logistic regression model
      demonstrated that subject age and gender, smoking, and the FcgammaRIIa genotype
      were significantly associated with severity of chronic periodontitis. For
      smokers, a significant over-representation of FcgammaRIIa-H/H131 in the patient
      group compared to the control group (patients versus controls: 35.1% versus
      19.0%; P = 0.03). Additionally, smokers with FcgammaRIIa-H/H131 exhibited
      significantly greater mean CAL (mean +/- SE: 3.44 +/- 0.16 mm) than those with
      FcgammaRIIa-R/H131 (2.91 +/- 0.14 mm) and R/R131 (2.82 +/- 0.16 mm) (P = 0.04).
      There was no association between FcgammaRIIa genotype and the disease
      susceptibility or severity in subjects who had never smoked. CONCLUSIONS: Our
      results suggest that the FcgammaRIIa-H/H131 genotype may be associated with
      chronic periodontitis risk (and disease severity) in Caucasian smokers. Further
      studies with families and studies of mechanisms are necessary to help establish
      the extent to which this is a genetic determinant of periodontal diseases.

PMID- 15152815
TI  - Specific pro-apoptotic fibronectin fragments modulate proteinase expression in
      periodontal ligament cells.
AB  - BACKGROUND: During inflammation and periodontal disease, the extra-cellular
      matrix protein fibronectin (FN) is degraded into fragments whose activities
      differ from those of the intact molecule. In periodontal ligament cells in vitro,
      some fragments elevate the expression of matrix metalloproteinases and serine
      proteinases, while others induce apoptosis through a mechanism regulated by
      caspase proteases and specific signaling pathways. In this study, we investigated
      whether the pro-apoptotic V+H- fibronectin fragment modulates proteinase
      expression as part of the apoptotic mechanism in periodontal ligament cells. The
      importance of this study is that a structurally similar fibronectin fragment
      found in vivo (40-kDa) is associated with periodontal disease status. However,
      the recombinant V+H- FN protein which is structurally and functionally similar to
      the in vivo 40-kDa fragment was chosen as the focus of these studies over the in
      vivo fragment because of the ability to readily produce and purify large
      quantities of recombinant fragments for detailed studies. Thus, findings from
      this study relate to our understanding of how the extracellular matrix of the
      periodontal ligament in an inflamed environment may contribute to periodontal
      disease and its progression. METHODS: We used substrate zymography, reverse
      zymography, proteinase inhibitors, and partial sequencing to investigate whether
      the pro-apoptotic V+H- fibronectin fragment modulates proteinase expression as
      part of this apoptotic mechanism. RESULTS: Incubation with the V+H- fragment
      reduced the expression of all gelatinolytic proteinases and inhibitors commonly
      expressed by periodontal ligament cells. In the presence of caspase inhibitors,
      inhibitors known to suppress apoptosis, however, the reduced proteinase profile
      was rescued, showing that caspase inhibitors were able to reverse the reduced
      proteinase profile and indicating that caspase-mediated pathways are pertinent to
      fibronectin-fragment-mediated matrix metalloproteinase expression. In addition,
      the V+H- fragment also triggered the expression of a unique high molecular weight
      gelatinolytic proteinase of approximately 200 kDa. This proteinase was a serine
      proteinase, whose identity is not known. CONCLUSION: These findings suggest that
      matrix-degrading proteinases may be involved in apoptosis as part of a unique
      mechanism of periodontal tissue breakdown, in which novel proteinases may help
      execute the dissolution of the extracellular matrix.

PMID- 15152816
TI  - Clinical relevance of adjunctive minocycline microspheres in patients with
      chronic periodontitis: secondary analysis of a phase 3 trial.
AB  - BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with
      minocycline microspheres resulted in significant reductions in patient mean
      probing depths as compared to scaling and root planing (SRP) alone. The objective
      of the present study was to evaluate clinical relevance of these changes within
      the trial using proposed site-based criteria. METHODS: A total of 499 patients
      with moderate to advanced chronic periodontitis were enrolled in a multi-center
      trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline
      microspheres. Subjects received complete probing examinations including the
      measurement of probing depths at baseline, and 1 and 3 months. Probing depth
      reductions were tabulated by treatment, examination time, and baseline depths,
      and inter-group differences were evaluated with logistic regression models for
      correlated data. RESULTS: Significantly more sites treated with adjunctive
      minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3
      (P = 0.01) months as compared to sites treated with SRP alone, both in the
      overall population and in smokers. In addition, significantly more sites
      decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP
      alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05).
      CONCLUSION: This secondary analysis indicates that treatment with SRP plus
      minocycline microspheres is consistently more effective than SRP alone in
      providing clinically relevant site-based responses in patients with chronic
      periodontitis.

PMID- 15152817
TI  - Inhibitory effect of a novel bisphosphonate, TRK-530, on dental calculus
      formation in rats.
AB  - BACKGROUND: A newly developed bisphosphonate, TRK-530 (disodium dihydrogen[4
      (methylthio)phenylthio]methanebisphosphonate), has recently been reported to show
      anti-inflammatory and anti-bone-resorbing activity. Since bisphosphonates have
      been shown to inhibit the formation of calcium-phosphate crystals in vitro, TRK
      530 may inhibit the formation of dental calculus. Therefore, the present study
      was performed to examine whether this compound has such an effect. METHODS: Three
      groups of Wistar rats fed a calculogenic diet (RC16) were treated with TRK-530 in
      drinking water at concentrations of 0 (control group), 0.75, and 1.5 mM. Another
      group received a daily subcutaneous injection of TRK-530 at a dose of 2.25
      micromoles/rat, which was assumed to correspond to the maximum amount of this
      compound absorbed from the intestine when rats received 1.5 mM TRK-530 in
      drinking water. Rat dental calculus formation was evaluated. The crystalline
      nature of dental calculus was studied by x-ray diffraction analysis. Finally, the
      effects of TRK-530 on the precipitation of calcium-phosphate from solution were
      tested in vitro. RESULTS: TRK-530 in drinking water inhibited dental calculus
      formation dose-dependently. However, subcutaneous injection of TRK-530 did not
      have any significant effect, suggesting that the anticalculus effect of TRK-530
      in drinking water was topical, not systemic. The calculus that formed in both the
      control and experimental groups was primarily hydroxyapatite, a main constituent
      of human dental calculus. TRK-530 inhibited the precipitation of calcium
      phosphate from solution in vitro. CONCLUSIONS: TRK-530 inhibited the formation of
      dental calculus in a dose-dependent fashion via a local effect. Inhibition of the
      precipitation of calcium-phosphate from solution might be involved in the
      anticalculogenic mechanism of this drug.

PMID- 15152818
TI  - Soluble cell adhesion molecules in gingival crevicular fluid in periodontal
      health and disease.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) are cell surface proteins involved in
      the binding of cells to each other, to endothelial cells, or to the extracellular
      matrix. The soluble forms of CAMs (sCAMs) are thought to be produced by
      proteolytic cleavage from the cell surface and are shed into the gingival
      crevicular fluid (GCF). The aim of this study was to investigate whether sCAMs,
      sICAM-1, sVCAM-1, and sE-Selectin were present in GCF in both periodontal health
      and disease and to examine their relationship with periodontal inflammation.
      METHODS: GCF was collected from a clinically healthy, a gingivitis, and a
      periodontitis site in 29 subjects with chronic periodontitis and from a single
      clinically healthy site in 22 subjects without chronic periodontitis. The volume
      of GCF was measured and each sample was analyzed for sCAMs by enzyme-linked
      immunosorbent assay (ELISA). The effect of treatment (oral hygiene instruction,
      scaling and root planing) on the levels of sCAMs in each site of the diseased
      group was also investigated. RESULTS: Statistically significant differences (P <
      0.05) were found between the levels of sVCAM-1 in periodontal health and disease.
      These results indicate that changes in the levels of sCAMs may be a sensitive
      indicator to differentiate healthy sites from those with periodontitis.
      Statistically significant changes in the levels of sICAM-1 were recorded after
      treatment (P < 0.05). CONCLUSIONS: Further studies are required to establish if
      these potential biomarkers will enable the identification of those sites most at
      risk for disease progression and also evaluate the response to treatment, thereby
      playing a preventive role in the pathogenesis of periodontal disease.

PMID- 15152819
TI  - Comparison of the use of a toothpick holder to dental floss in improvement of
      gingival health in humans.
AB  - BACKGROUND: Although advances have been made in modulation of host inflammatory
      response in periodontal therapy, it is important to control the bacterial
      challenge to the host immune system through conventional therapy and improvement
      of personal oral hygiene. Although toothbrushing is generally performed,
      interdental cleaning is not as common. This study compared the use of dental
      floss to a toothpick holder in the improvement of gingival health. METHODS:
      Participants were examined and those with clinical gingivitis or slight chronic
      periodontitis were included in the study. O'Leary plaque, interproximal plaque
      index (IPI), and Eastman interdental bleeding index scores (EIBI) were recorded
      at baseline and following appointments. Forty-two females and 13 males ranging
      from 18 to 50 years in age were randomly divided into either a dental flossing
      group or toothpick holder using group. Each was given instructions in the use of
      the oral hygiene device and examined 2, 6, and 12 weeks following baseline. At 12
      weeks, 27 floss users and 20 toothpick-holder users completed the study. RESULTS:
      Plaque scores were reduced in both groups as the study progressed. Mean O'Leary
      plaque scores decreased significantly for both methods from baseline to week 12
      (P < 0.05). The EIBI and IPI scores decreased in mean scores over time for each
      method (P < 0.05). A correlation was found between the O'Leary plaque index and
      the IPI scores (P < 0.05). CONCLUSION: The results of this study found that the
      use of dental floss or toothpick holder resulted in no significantly different
      effect in the improvement of gingival health.

PMID- 15152820
TI  - Lymphocyte numbers and function in relation to periodontitis and smoking.
AB  - BACKGROUND: T and B lymphocytes play important roles in periodontitis. Smoking is
      considered a risk factor for periodontitis and may exert its negative effects
      through leukocytes. Taking smoking into consideration, the aim of this study was
      to analyze numbers of circulating T (CD3+) cells and their CD4+ and CD8+
      subpopulations, B (CD19+) cells, and T-cell proliferative capacity in
      periodontitis. METHODS: Lymphocyte immunophenotyping for T cells, their CD4+ and
      CD8+ subsets, and B cells was performed on peripheral blood from 76 periodontitis
      patients and 36 controls. Proliferative capacity of T cells was determined in
      whole-blood lymphocyte culture assays after mitogenic stimulation. RESULTS: Total
      T cells, CD4+ and CD8+ subpopulations, and responsiveness to specific T-cell
      stimuli did not differ between patients and controls; in addition, B cells were
      not significantly elevated in periodontitis patients. However, more periodontal
      breakdown in smoking patients was associated with higher numbers of CD3+ T cells,
      as well as with CD4+ and CD8+ T-cell subsets, and increased T-cell proliferation.
      Numbers of B cells were not affected by smoking. CONCLUSIONS: The increased
      numbers of T-cells and elevated T-cell responsiveness in patients who smoke may
      be one of several explanations why smoking is a risk factor for periodontitis.
      The mechanism of how T-cell function contributes to increase the severity of
      periodontal breakdown in smoking periodontitis patients needs to be investigated
      further.

PMID- 15152821
TI  - Guided bone regeneration may be negatively influenced by nicotine administration:
      a histologic study in dogs.
AB  - BACKGROUND: A series of animal and in vitro data confirms that nicotine impairs
      bone healing, diminishes osteoblast function, and causes autogenous bone graft
      morbidity. Therefore, this study aimed to investigate the impact of nicotine on
      the healing of bone defects treated by the guided bone regeneration (GBR)
      principle. METHODS: Sixteen mongrel dogs were used. One defect was surgically
      created bilaterally and randomly assigned as an expanded polytetrafluoroethylene
      (ePTFE) membrane site or a non-membrane control site. The animals were randomly
      assigned to one of the following groups: group 1, placebo (n = 8) and group 2,
      subcutaneous administration of nicotine (2 mg/kg) twice daily (n = 8). After 4
      months, the animals were sacrificed and the specimens routinely processed for
      semi-serial decalcified sections. The evaluated parameters were bone height, bone
      width, bone density, and bone area of newly formed bone. RESULTS: Intergroup
      analysis (Kruskal-Wallis) showed that membrane-protected defects in the placebo
      group demonstrated an increased bone area when compared to membrane-protected
      defects in the nicotine group and non-membrane sites, regardless of nicotine
      administration (P < 0.05). In addition, nicotine administration significantly
      affected bone density in membrane- and non-membrane-protected sites (P < 0.05).
      CONCLUSIONS: Within the limits of the present study, nicotine might affect, but
      not prevent, bone healing in defects treated by guided bone regeneration. The
      mechanisms of this effect should be investigated further.

PMID- 15152822
TI  - Initial implant position determines the magnitude of crestal bone remodeling.
AB  - BACKGROUND: The ability to predict the amount of bone remodeling around implants
      is important for a stable and predictable esthetic result. The purpose of this
      study was to investigate the amount of radiographic bone remodeling that occurs
      over time using a one-piece implant system. METHODS: Twenty-seven patients
      receiving implants in the maxilla and 15 receiving implants in the mandible were
      included in the study. All implants were placed with a non-submerged surgical
      technique with varying locations of the rough-smooth border with respect to the
      alveolar crest. Clinical exams and radiographs were taken on the day of implant
      placement, at 6 months, and annually up to 5 years. Linear measurements from
      digitized radiographs were made from the implant shoulder to the first bone-to
      implant contact at all time points. RESULTS: A significant amount of bone
      remodeling compared to baseline occurred for all implants at the 6-month follow
      up visit (1.10 mm), with the remaining time points showing virtually no change
      (0.1 mm). A relationship was found between the amount of bone remodeling and the
      location of the rough-smooth border with respect to the alveolar crest. Those
      implants with the rough-smooth border surgically placed below the crest had, on
      average, a greater amount of remodeling at 6 months (average 1.72 mm) than
      implants with the rough-smooth border placed at or near the crest (average 0.68
      mm). In both situations, this remodeling: 1) occurred early (within 6 months), 2)
      reached a similar level, and 3) remained virtually unchanged up through 60 months
      (0.05 mm). CONCLUSIONS: A physiologic dimension appears to exist between the bone
      and the implant-crown interface around one-piece implants that is established
      early and maintained over time. These results are significant because they
      demonstrate in patients that the magnitude of initial bone remodeling around
      these one-piece dental implants is dependent on the positioning of the rough
      smooth border of the implant in an apico-coronal dimension. Furthermore, the
      dimension, from the crown-implant interface to the first bone-to-implant contact,
      is consistent with the formation of a biologic width similar to that found around
      the natural dentition.

PMID- 15152823
TI  - The in vivo expression of membrane-bound CD14 in periodontal health and disease.
AB  - BACKGROUND: Membrane-bound CD14 (mCD14) is a myeloid differentiation antigen
      expressed on monocytes/macrophages and neutrophils. It is a key molecule
      responsible for the innate recognition of bacteria by host cells and functions as
      an important receptor for bacterial lipopolysaccharide. This study investigated
      the in vivo expression profile and levels of mCD14 in healthy and diseased
      gingival tissues. METHODS: Gingival biopsies were obtained from 24 patients with
      chronic periodontitis, including 22 periodontal pocket tissues, 13 clinically
      healthy tissues, and 18 inflamed connective tissues (i.e., granulation tissues).
      Gingival biopsies from seven periodontally healthy subjects were used as
      controls. mCD14 was detected by immunohistochemistry. RESULTS: mCD14 was detected
      in 21 of 22 periodontal pocket tissues and all other categories of tissues. The
      mCD14-positive cells were mainly confined to the gingival epithelium-connective
      tissue interface. The expression levels in periodontally healthy subjects were
      significantly higher than in the patients. Within the patients, clinically
      healthy tissues showed greater levels of mCD14 than periodontal pocket tissues
      and granulation tissues. CONCLUSIONS: mCD14 was commonly expressed in both
      healthy and diseased gingival tissues and was predominantly confined to the
      epithelium-connective tissue interface. The positive relationship observed
      between mCD14 expression levels and periodontal health may imply that mCD14 is
      associated with favorable host responses to bacterial challenge and contributes
      to maintaining periodontal homeostasis.

PMID- 15152824
TI  - Smoking may affect root coverage outcome: a prospective clinical study in humans.
AB  - BACKGROUND: Cigarette smoking has been shown to negatively influence healing
      following periodontal therapeutic procedures. Therefore, the aim of this study
      was to evaluate the impact of smoking on clinical outcome of root coverage
      following subepithelial connective tissue graft (CTG) surgery. METHODS: Eighteen
      defects were treated in 15 patients (seven smokers and eight non-smokers) who
      presented canine and pre-molar Miller Class I and II recessions. CTG was
      performed and clinical measurements were obtained at baseline, and 30, 60, 90,
      and 120 days after surgery. Clinical measurements included plaque and gingival
      indexes, gingival recession, probing depth, clinical attachment level, gingival
      thickness, and keratinized tissue width. RESULTS: Intragroup analysis showed that
      CTG was able to promote root coverage, increase gingival thickness, and improve
      clinical attachment level in both groups (P < 0.05). On the other hand,
      intergroup analysis demonstrated that smokers presented with a lower percentage
      of root coverage (58.84% +/- 13.68% versus 74.73% +/- 14.72%), less clinical
      attachment level gain (2.54 +/- 0.79 mm versus 2.00 +/- 1.04 mm), and deeper
      probing depths (1.56 +/- 0.53 mm versus 2.35 +/- 0.67 mm) than non-smokers (P <
      0.05). Moreover, 4 months after CTG, smokers presented more keratinized tissue
      compared to non-smokers (3.30 +/- 0.86 mm versus 4.50 +/- 1.16 mm) (P < 0.05).
      CONCLUSION: Within the limits of the present study, it can be concluded that
      cigarette consumption may present a negative impact on root coverage outcome by
      CTG and, therefore, may represent one more challenge for periodontal plastic
      therapy.

PMID- 15152825
TI  - Relationship of Actinobacillus actinomycetemcomitans serotype b to aggressive
      periodontitis: frequency in pure cultured isolates.
AB  - BACKGROUND: To our knowledge, the association of the five serotypes of
      Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) to the new
      diagnostic classification scheme defined by the American Academy of
      Periodontology in 1999 has not yet been described. The goal of this study was to
      characterize the frequencies of the five serotypes of A. actinomycetemcomitans in
      A. actinomycetemcomitans isolates from various forms of periodontitis using both
      old and new diagnostic classifications and to determine the relationships between
      serotype and age and clinical diagnosis. METHODS: A total of 345 A.
      actinomycetemcomitans isolates from 115 A. actinomycetemcomitans culture-positive
      subjects (mean age 38.0 +/- 18.3 years, 59% female) were collected. Based on the
      new classifications, 33 subjects had aggressive periodontitis and 82 chronic
      periodontitis. According to old classifications, there were six prepubertal
      periodontitis (PPP), 12 localized juvenile periodontitis (LJP), 15 post-localized
      juvenile periodontitis (PLJP), 28 refractory periodontitis (Ref-P), and 54 adult
      periodontitis (AP) cases. Serotypes of A. actinomycetemcomitans were determined
      by an indirect immunofluorescence assay using serotype-specific polyclonal
      antisera to A. actinomycetemcomitans strains ATCC 29523, ATCC 43728, ATCC 33384,
      IDH 781 and IDH 1705 (serotype a, b, c, d, and e, respectively). Proportions of
      serotype b were examined between different diagnostic and age groups with a Z
      test for proportions. RESULTS: Most subjects (n = 100, 86.96%) were infected with
      a single serotype (22 serotype a, 44 serotype b, 30 serotype c, 1 serotype d, and
      3 serotype e). There were 11 subjects (9.57%) with two serotypes and two subjects
      (1.74%) with 3 serotypes. Two individuals had isolates lacking any detectable
      serotype antigen. Serotype b was the predominant serotype in children under 18
      years of age and young adults between 19 to 35 years, although serotype b status
      was not significantly associated with age. Serotypes d and e were not found in
      patients under 35 years old. In 62 adult patients, one subject had serotype d and
      three had serotype e. Serotype b was the most common serotype in aggressive
      periodontitis (60.61%). The proportion of cases with serotype b was significantly
      higher in aggressive periodontitis compared to chronic periodontitis (P = 0.031).
      Other serotypes were not significantly associated with new diagnostic categories.
      Serotypes d and e were not detected in aggressive periodontitis. CONCLUSION: The
      results of this study show that proportions of serotype b of A.
      actinomycetemcomitans are significantly greater in culture-positive patients with
      aggressive periodontitis than those with chronic periodontitis.

PMID- 15152826
TI  - A multicenter comparative study of two root coverage procedures: coronally
      advanced flap with addition of enamel matrix proteins and subpedicle connective
      tissue graft.
AB  - BACKGROUND: Free grafts, pedicle flaps, and barrier membranes have been used to
      cover exposed root surfaces. The aim of the present study was to evaluate the
      clinical efficacy of a coronally advanced flap procedure with the additional use
      of enamel matrix protein derivative (EMD) to treat gingival recession and to
      compare it to the subpedicle connective tissue graft procedure (CTG). METHODS:
      The study was conducted in six different periodontal clinics. Miller Class I or
      II buccal recession type defects in the anterior or premolar teeth were treated
      in 70 consecutive patients, 30 with EMD and 40 with CTG. At baseline and 6 and 12
      months post-surgical treatment, vertical recession defect, defined as the
      distance from cemento-enamel junction to gingival margin; width of keratinized
      tissue; and probing depth were recorded and the percentage of coverage of the
      original defect was calculated. Statistical analyses consisted of t-test,
      analysis of variance, and analysis of covariance. RESULTS: At 6 months, percent
      of root coverage was 77.4% +/- 11.92% in EMD and 84.1% +/- 11.97% in CTG
      (statistically significant at P = 0.024). At 12 months, percent of root coverage
      in EMD was 71.7% +/- 16.14% and 87.0% +/- 12.22% in CTG; again, differences
      between groups were statistically significant (P < 0.001). Differences between
      the 6- and 12-month vertical recession defect and percent of root coverage
      recordings within each group were also statistically significant. CONCLUSIONS:
      The connective tissue graft procedure was superior to the coronally positioned
      flap with the addition of enamel matrix proteins derivative in percentage of
      coverage and increase in width of keratinized tissue. The EMD procedure is a
      predictable treatment for root coverage that is relatively easy to perform and
      presents low patient morbidity, and is appropriate especially where a substantial
      increase in the width of keratinized tissue is not of prime importance.

PMID- 15152827
TI  - Sarcoidosis with gingival involvement: a case report.
AB  - BACKGROUND: The case outlined is a rare presentation of sarcoidosis intraorally
      associated with gingival ulceration. METHODS: The diagnosis was made following a
      gingival biopsy. RESULTS: The patient was subsequently referred to a physician
      for clinical management and the condition resolved without active treatment.
      CONCLUSIONS: Sarcoidosis should be considered in the differential diagnosis of
      persistent swellings and ulceration of the oral mucosa. Intraoral sarcoid lesions
      are often the first indication of systemic involvement. It is important to make
      the diagnosis and monitor the condition as sarcoidosis is progressive if
      untreated in a small number of those affected.

PMID- 15152828
TI  - Successful treatment of oral lichen planus-like chronic graft-versus-host disease
      with topical tacrolimus: a case report.
AB  - BACKGROUND: Bone marrow transplantation (BMT) is a common treatment used for
      deficiencies of host marrow or in the control of blood malignancies. Post
      allogeneic BMT complications include graft-versus-host disease (GVHD). GVHD
      occurs when immunologically active T lymphocytes are transplanted into an
      immunosuppressed recipient who is genetically disparate from the donor. In this
      case report we describe the occurrence of oral lichen planus-like lesions as the
      first manifestation of chronic GVHD (c-GVHD) and the subsequent management of
      this disease with topical tacrolimus. METHODS: Diagnostic aids included routine
      histology and direct immunofluorescence studies to rule out immunobullous
      diseases and to confirm the c-GVHD. Treatment consisted of topical application of
      0.1% tacrolimus ointment three times a day. RESULTS: Routine histology confirmed
      the clinical diagnosis of oral lichen planus-like c-GVHD. Treatment with
      tacrolimus ointment completely resolved the oral lesions after 2 months of
      therapy. CONCLUSIONS: Topical tacrolimus at low concentrations (0.1%) shows
      promise in the management of oral lichen planus-like c-GVHD. Controlled studies
      are necessary to assess the efficacy, the duration of therapy required for
      effective results, and the safety of this treatment over the long-term.

PMID- 15152829
TI  - A method to enhance determining the clinical relevance of periodontal research
      data: number needed to treat (NNT).
AB  - It would be advantageous if clinical trials reported both statistical and
      clinically meaningful results. In this regard, determination of the number of
      sites that would need to be treated in a test group to provide a beneficial
      result or prevent an adverse event at one additional site beyond the control
      group would provide useful information. This editorial addresses the use of NNT
      (number needed to treat) calculations to enhance determining the clinical
      relevance of periodontal research findings. The application, requirements for
      use, benefits, and limitations of employing NNT calculations are discussed.

PMID- 15152830
TI  - Characteristics of porcine circovirus-2 replication in lymphoid organs of pigs
      inoculated in late gestation or postnatally and possible relation to clinical and
      pathological outcome of infection.
AB  - In this study, the characteristics of porcine circovirus-2 (PCV2) replication
      (infectious virus titrations, distribution, and immunophenotyping of infected
      cells) in lymphoid organs were examined and related to the development of
      clinical signs and histological lesions in 26 piglets that had been inoculated
      with PCV2 either in utero or at 1 day of age. Piglets inoculated in utero at 92
      or 104 gestational days (n = 12) were collected by Caesarean section at term and
      either sacrificed immediately or kept in isolators and allowed to live
      postnatally until 35 days postinoculation (PI). Caesarean-derived piglets
      inoculated at 1 day of age (n = 14) were sacrificed at 10, 21, 35, 42, and 49
      days PI. Spleen and lymph nodes were collected for virologic and
      histopathological examinations. Clinical signs were not observed in any of the
      piglets. High virus titers (10(4.5-5.7) TCID50/g [TCID refers to tissue culture
      infectious dose]) were detected in 6 of the 26 piglets. Three of these 6 piglets
      were euthanized at 10 days PI, and infected cells of the monocyte-macrophage
      lineage (SWC3+, CD14+, and sialoadhesin [Sa]+ cells) and infected cells bearing
      lymphocyte markers (CD4+, CD8+, and immunoglobulin M+ cells) were identified by
      double-immunofluorescence labeling on serial cryostat sections. The other 3
      piglets were euthanized at 21 and 35 days PI, and the majority of infected cells
      were SWC3+, CD14+, and Sa-. The absence of Sa in these infected cells, together
      with their localization in lymphocyte-dependent regions, suggests that they were
      infiltrating monocytic cells. Sialoadhesin is highly expressed in differentiated
      macrophages and not in peripheral blood mononuclear cells. In all 6 piglets with
      high virus titers, lymphocyte depletion and infiltration of monocytic cells were
      observed. In the remaining 20 piglets with virus titers less than 10(4.5)
      TCID50/g, the majority of infected cells were SWC3+, CD14+, and Sa+. In
      conclusion, it can be stated that high PCV2 titers in lymphoid organs may lead to
      the development of histological lesions similar to those observed in pigs with
      postweaning multisystemic wasting syndrome without causing disease. Furthermore,
      in lymphoid organs with high virus titers, infection occurs mainly in
      infiltrating monocytic cells and to a limited extent in cells bearing lymphocyte
      markers.

PMID- 15152831
TI  - West Nile virus infection in free-ranging squirrels in Illinois.
AB  - West Nile virus (WNV) infection was diagnosed in 13 gray squirrels (Sciurus
      carolinensis) and 3 fox squirrels (Sciurus niger) that were observed with
      neurologic signs before death or found dead. All 16 had gliosis throughout all
      sections of the brain. Most had lymphoplasmacytic encephalitis or
      meningoencephalitis, many with admixed neutrophils. Neuronal necrosis and
      neuronophagia were also prominent features. West Nile virus antigen was
      demonstrated in the brain, spleen, heart or kidney in 10 of 13 gray squirrels and
      3 of 3 fox squirrels by immunohistochemistry. Nucleic acid amplification tests
      (NAATs) confirmed the presence of WNV in the brain or spinal cord of 10/10 gray
      squirrels and 1/3 fox squirrels tested. Viral levels were quantified in various
      tissues of selected gray squirrels, and titers were highest in spleen and brain,
      with no virus detected in serum. This is the first description of lesions
      associated with WNV infection in gray and fox squirrels.

PMID- 15152832
TI  - Development of quantitative competitive-reverse transcriptase-polymerase chain
      reaction for detection and quantitation of avian leukosis virus subgroup J.
AB  - Infection with avian leukosis virus subgroup J (ALV-J) causes severe economic
      losses in the broiler industry by increasing mortality, producing tumors, and
      decreasing weight gain in chickens. The quantitation of ALV-J is difficult
      because of its failure to produce a cytopathic effect in cell culture systems and
      the nonspecificity of antigen-capture enzyme-linked immunosorbent assay (ELISA)
      tests. This study was performed to develop a quantitative competitive-reverse
      transcriptase-polymerase chain reaction (QC-RT-PCR) method based on
      coamplification of ALV-J genomic RNA and a known amount of a synthesized RNA
      competitor. The 369 bp RNA competitor was constructed by restriction enzyme
      treatment of an ALV-J specific 545 bp PCR product, ligation, transformation into
      Escherichia coli, and in vitro transcription. The competitor contained the same
      amplification primer annealing sites and sequence as the original viral RNA,
      except that it had a 176 bp internal deletion. Coamplified RT-PCR products were
      visualized by electrophoresis and ethidium bromide staining, and fluorescences
      were quantified using computer-assisted image analysis. The sensitivity of this
      new QC-RT-PCR method was 25 fg of viral RNA, and 10-fold dilutions were
      differentiable. This method allowed absolute and relative quantification of ALV-J
      RNA copy numbers and was simpler than previously published methods for ALV-J
      quantification.

PMID- 15152833
TI  - Comparison of a commercial H1N1 enzyme-linked immunosorbent assay and
      hemagglutination inhibition test in detecting serum antibody against swine
      influenza viruses.
AB  - Recently a commercial enzyme-linked immunosorbent assay (ELISA) kit for detecting
      antibody against H1N1 swine influenza virus (SIV) has been made available to
      diagnosticians and veterinary practitioners. Because the hemagglutination
      inhibition (HI) test has been considered the standard test for SIV serology,
      diagnostic performance of the new ELISA was evaluated using positive (n = 60) and
      negative (n = 188) serum samples from young pigs with known status of SIV
      infection and compared with that of the HI test. Both ELISA and HI test
      identified all negative animals correctly. None of the serum samples (n = 64)
      from pigs inoculated with H3N2 SIV was positive by ELISA for SIV antibody. The
      H1N1 SIV antibody detectable by ELISA appears to develop more slowly in
      comparison with antibody detectable by HI test. Although antibody was detected by
      HI test in all inoculated animals (n = 20) by day 7 postinoculation (PI),
      antibody was detected by ELISA in 0%, 75%, and 100% of the inoculated animals on
      days 7, 14, and 28 PI, respectively. Discrepancy in test results between the 2
      serologic tests appeared to be because of differences in antibody isotypes
      detected by each test. Enzyme-linked immunosorbent assay mainly detected IgG
      antibody, whereas the HI test detects IgM antibody very efficiently as well as
      IgG antibody. Collectively, the commercial ELISA is highly specific for antibody
      to H1N1 SIV but may not identify positive animals at the early stage of infection
      as effectively as the HI test, particularly when SIV is introduced to a naive
      swine population.

PMID- 15152834
TI  - Evaluation of five diagnostic methods for the detection and quantification of
      Myxobolus cerebralis.
AB  - Diagnostic methods were used to identify and quantify Myxobolus cerebralis, a
      myxozoan parasite of salmonid fish. In this study, 7-week-old, pathogen-free
      rainbow trout (Oncorhynchus mykiss) were experimentally infected with M.
      cerebralis and at 7 months postinfection were evaluated with 5 diagnostic assays:
      1) pepsin-trypsin digest (PTD) to detect and enumerate spores found in cranial
      cartilage, 2) 2 different histopathology grading scales that provide a numerical
      score for severity of microscopic lesions in the head, 3) a conventional single
      round polymerase chain reaction (PCR), 4) a nested PCR assay, and 5) a newly
      developed quantitative real-time TaqMan PCR. There were no significant
      differences (P > 0.05) among the 5 diagnostic assays in distinguishing between
      experimentally infected and uninfected control fish. The 2 histopathology grading
      scales were highly correlated (P < 0.001) for assessment of microscopic lesion
      severity. Quantification of parasite levels in cranial tissues using PTD and real
      time TaqMan PCR was significantly correlated r = 0.540 (P < 0.001). Lastly, 104
      copies of the 18S rDNA gene are present in the M. cerebralis genome, a feature
      that makes this gene an excellent target for PCR-based diagnostic assays. Also, 2
      copies of the insulin growth factor-I gene are found in the rainbow trout genome,
      whose detection can serve both as an internal quality control for amplifiable DNA
      and as a basis to quantify pathogen genome equivalents present in quantitative
      PCR assays.

PMID- 15152835
TI  - Age-stratified validation of an indirect Salmonella Dublin serum enzyme-linked
      immunosorbent assay for individual diagnosis in cattle.
AB  - Enzyme-linked immunosorbent assays (ELISAs) are routinely used for cattle herd
      diagnosis of Salmonella Dublin infection in many countries. It is also possible
      to use such tests for individual diagnosis. Passively transferred immunoglobulins
      may cause false-positive test results in young calves. Also, false-positive test
      results may be seen in recovered animals several months after infection. False
      negative results are seen in acutely infected animals, especially immature
      animals that are unable to produce a humoral antibody response to infection. To
      be able to interpret the individual animal test results, it is necessary to take
      age into account when validating the ELISA. In the present study an age
      stratified validation of an indirect Salmonella Dublin serum ELISA as predictor
      of bacterial excretion was performed using receiver-operating characteristic
      (ROC) analysis. Three age groups were formed according to the results of an
      exploratory analysis of the age effect on area under curve (AUC) of ROC curves.
      The AUC for the youngest age group (0-99 days) was 0.816 (SE = 0.033), which was
      significantly (z = 4.23, P < 0.0001) smaller than the 0.977 (SE = 0.019)
      estimated for the next age group (100-300 days). The oldest age group (> 300
      days) had an AUC of 0.905 (SE = 0.023), which was significantly different from
      the AUC of both the other age groups (z = 2.21, P = 0.027 when compared with the
      youngest age groups and z = 2.41, P = 0.016 when compared with the age group of
      100-300 days). The results showed that the indirect Salmonella Dublin serum ELISA
      is most valid for detection of infection in individual cattle from the age of 100
      days. Purpose-related test sensitivities and specificities were evaluated at
      different cutoff values.

PMID- 15152836
TI  - West Nile virus infection in reindeer (Rangifer tarandus).
AB  - West Nile virus (WNV) infection in 4 reindeer (Rangifer tarandus) resulted in
      lymphohistiocytic encephalomyelitis within the medulla oblongata and cervical
      spinal cord. Immunohistochemistry revealed WNV antigen within neurons and among
      mononuclear cell infiltrates. These represent the first known cases of clinical
      WNV infection in Cervidae. Clinical signs and lesions were similar to those
      described in horses. Nucleotide sequence of a 768-bp region of the WNV E
      glycoprotein gene revealed 1 nucleotide mutation, which resulted in a single
      amino acid substitution from a serine to a glycine (position 227 of E
      glycoprotein) when compared with the prototype WNV-NY99 strain (isolated from
      Bronx zoo flamingo 382-99).

PMID- 15152838
TI  - Malignant neoplasia in four alpacas.
AB  - Malignant neoplasia in 4 alpacas was characterized by acute onset of clinical
      signs and rapidly deteriorating condition. Postmortem examination revealed
      metastatic or multicentric neoplasia in the abdominal organs of alpacas 1, 3, and
      4 and an extensive thoracic mass in alpaca 2. Immunohistochemical stains
      supported a diagnosis of B-cell lymphosarcoma in alpacas 1-3 and a neuroendocrine
      neoplasm in alpaca 4.

PMID- 15152837
TI  - Increased concentration of GM1-ganglioside in cerebrospinal fluid in dogs with
      GM1- and GM2-gangliosidoses and its clinical application for diagnosis.
AB  - GM1- and GM2-gangliosidoses are lethal lysosomal diseases that are caused by a
      defect of acid hydrolases, resulting in the intralysosomal accumulation of the
      specific physiological substrates, GM1- and GM2-gangliosides, respectively. In
      the present study a method for the diagnosis of canine GM1-gangliosidosis was
      established using canine cerebrospinal fluid (CSF). The concentration of GM1
      ganglioside in CSF was determined by thin-layer chromatography-enzyme
      immunostaining using biotin-conjugated cholera toxin B, which specifically binds
      with GM1-ganglioside. The concentration of CSF GM1-ganglioside was increased in
      Shiba dogs with GM1-gangliosidosis, and the increased level was approximately
      proportional to the age of the dogs. The concentration was high in the affected
      dog even at 5 months of age, when Shiba dogs with GM1-gangliosidosis first
      manifest neurologic signs. In addition, the concentration of CSF GM1-ganglioside
      in a dog with the GM2-gangliosidosis 0 variant (Sandhoff disease) was also 7
      times the normal level. From these results it was concluded that this laboratory
      technique enables a definitive and early diagnosis of canine GM1-gangliosidosis
      even if tissues and organs cannot be obtained. However, because GM1-ganglioside
      can also be elevated in cases of GM2-gangliosidosis, it is necessary to assay for
      specific enzyme deficiencies to definitively separate GM1- from GM2
      gangliosidosis.

PMID- 15152839
TI  - Electron microscopic study of canine Babesia gibsoni infection.
AB  - Canine babesiosis is a tick-borne parasitic disease caused by the
      intraerythrocytic parasites, Babesia canis and Babesia gibsoni. A lethargic,
      weak, American Staffordshire Terrier (pit bull) dog, which had regenerative,
      normocytic, normochromic anemia, was shown by polymerase chain reaction analysis
      to be infected with B. gibsoni. Transmission electron microscopy of
      ethylenediamine tetraacetic acid-treated blood disclosed many well-preserved,
      intraerythrocytic babesia trophozoites. Four morphologic forms of babesia
      trophozoites are described (small spheres, small rods, irregular forms lacking
      pseudoinclusions, and large spheres having pseudoinclusions) and are compared
      with intraerythrocytic forms of B. canis and B. gibsoni described in other light
      and electron microscopic studies of in vivo and in vitro Babesia infections. This
      is the first detailed transmission electron microscopic study of canine B.
      gibsoni-infected red blood cells in North America.

PMID- 15152840
TI  - Effect of multiple sampling on diagnostic sensitivity.
AB  - Overall diagnostic sensitivity is the probability that a diagnostic procedure
      will detect an agent if the tested animal is indeed infected. The overall or
      effective sensitivity is a function of both the probability that the assay will
      detect the agent if it is present in the sample tested and the probability that
      the agent will be present in the sample tested if the animal is infected with the
      agent. Thus, even with a highly sensitive assay, the probability of detecting an
      infected animal may be low or nil if the sampling procedure failed to capture the
      agent in samples tested by the assay. In this article, it is demonstrated how
      increased frequency of testing, such as testing multiple subsamples, can have a
      profound effect on increasing the overall sensitivity of a diagnostic procedure.

PMID- 15152841
TI  - Effect of temperature on the detection of porcine epidemic diarrhea virus and
      transmissible gastroenteritis virus in fecal samples by reverse transcription
      polymerase chain reaction.
AB  - The effect of storage temperature was determined for the detection of porcine
      epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) in
      fecal samples from experimentally and naturally infected pigs by multiplex
      reverse transcription-polymerase chain reaction (RT-PCR). To examine the effect
      of storage temperature on the ability to detect PEDV and TGEV RNA by multiplex RT
      PCR, fecal samples were stored for different temperatures (4, 21, 36, and 45 C)
      before extracting viral RNA. The PEDV and TGEV nucleic acids in fecal samples
      were stable up to 3 days at 4 C. The PEDV and TGEV nucleic acids were
      consistently detected in fecal samples up to 60 hours at 21 C and 24 hours only
      at 36 and 45 C. Thereafter, the number of positive signals declined. Positive
      signals were detected in fecal samples stored at 4 C by 240 hours. The PEDV and
      TGEV nucleic acids were consistently detected in fecal samples up to 60 hours at
      21 C and 24 hours only at 36 and 45 C. The results of this study suggested that
      storage temperature has significant effect on the detection of PEDV and TGEV
      nucleic acids from fecal samples by multiplex RT-PCR.

PMID- 15152842
TI  - Use of immunohistochemical marker calretinin in the diagnosis of a diffuse
      malignant metastatic mesothelioma in an equine.
AB  - Mesotheliomas are rarely reported in animal species. In this report, the
      occurrence of a diffuse, metastatic mesothelioma in a 6-year-old gray Arabian
      mare is described. The mare was presented on clinical examination with ascites,
      bilateral pleural effusion, and pleural roughening. Necropsy revealed abundant
      fluid in the abdominal and thoracic cavities. The surface of all organs was thick
      and fibrosed with multiple raised nodules and hemorrhages. Histology was
      characteristic of a generalized, biphasic mesothelioma with vascular and lymph
      nodes metastases. It is believed that the primary tumor developed in the
      pericardium and spread through lymphatics. In this report, calretinin was used as
      an immunohistochemical marker in the diagnosis of mesothelioma in an equine
      species for the first time.

PMID- 15152843
TI  - Detection of three avian respiratory viruses by single-tube multiplex reverse
      transcription-polymerase chain reaction assay.
AB  - Acute respiratory tract infections are leading causes of morbidity in poultry
      farms throughout the world. Avian pneumovirus (APV), avian influenza virus (AIV),
      and Newcastle disease virus (NDV) have been recognized as the most important
      pathogens of both chicken and turkeys. Single-virus reverse transcription
      polymerase chain reaction (sRT-PCR) assays are used extensively to detect these
      viruses in clinical samples. This study reports the development and evaluation of
      a single-tube multiplex RT-PCR (mRT-PCR) assay for simultaneous and specific
      detection of APV, AIV, and NDV. Specific primers for each virus were selected
      that amplified products of predicted sizes from each virus in the mRT-PCR as well
      as in the sRT-PCR assays (438, 218, and 532 bp for APV, AIV, and NDV,
      respectively). The sensitivity and specificity of mRT-PCR assay were compared
      with those of the sRT-PCR. The mRT-PCR assay was as sensitive as the sRT-PCR
      assays because virus detection limits were similar in both assays. The detection
      limits of mRT-PCR assay were 10(0.5) tissue culture infective dose (50%)
      (TCID50)/ml, 10(1.2) TCID50/ml, and 10(0.7) TCID50/ml for APV, AIV, and NDV,
      respectively. Overall, there was an excellent correlation between mRT-PCR and sRT
      PCR assays. No product amplification was obtained with nucleic acid from
      infectious bronchitis virus and reovirus using these primer sets. In summary, mRT
      PCR assay holds potential to be an economical and rapid diagnostic method for the
      simultaneous detection of 3 avian respiratory viruses in chickens and turkeys.

PMID- 15152844
TI  - Granulomatous lymphadenitis and splenitis associated with Monocillium indicum
      infection in a dog.
AB  - This report describes severe generalized granulomatous lymphadenitis and
      splenitis in a 5-year-old, spayed female, Rottweiler dog with anorexia and
      diarrhea. There was replacement or effacement of much of the parenchyma of the
      lymph nodes and spleen by sheets of macrophages, multinucleated giant cells, and
      myriad nonpigmented fungal organisms, most of which appeared to be intracellular.
      These organisms were very pleomorphic, including large chlamydospore-like cells,
      small round yeast-like cells, and septate hyphae. A fungus identified as
      Monocillium indicum was isolated from lymph node tissue. To the authors'
      knowledge, this is the first report of infection with Monocillium in either
      humans or other animals.

PMID- 15152845
TI  - The importance of meta-ethics in engineering education.
AB  - Our shared moral framework is negotiated as part of the social contract. Some
      elements of that framework are established (tell the truth under oath), but other
      elements lack an overlapping consensus (just when can an individual lie to
      protect his or her privacy?). The tidy bits of our accepted moral framework have
      been codified, becoming the subject of legal rather than ethical consideration.
      Those elements remaining in the realm of ethics seem fragmented and inconsistent.
      Yet, our engineering students will need to navigate the broken ground of this
      complex moral landscape. A minimalist approach would leave our students with
      formulated dogma--principles of right and wrong such as the National Society for
      Professional Engineers (NSPE) Code of Ethics for Engineers--but without any
      insight into the genesis of these principles. A slightly deeper, micro-ethics
      approach would teach our students to solve ethical problems by applying
      heuristics--giving our students a rational process to manipulate ethical dilemmas
      using the same principles simply referenced a priori by dogma. A macro-ethics
      approach--helping students to inductively construct a posteriori principles from
      case studies--goes beyond the simple statement or manipulation of principles, but
      falls short of linking personal moral principles to the larger, social context.
      Ultimately, it is this social context that requires both the application of
      ethical principles, and the negotiation of moral values--from an understanding of
      meta-ethics. The approaches to engineering ethics instruction (dogma, heuristics,
      case studies, and meta-ethics) can be associated with stages of moral
      development. If we leave our students with only a dogmatic reaction to ethical
      dilemmas, they will be dependent on the ethical decisions of others (a denial of
      their fundamental potential for moral autonomy). Heuristics offers a tool to deal
      independently with moral questions, but a tool that too frequently reduces to
      casuistry when rigidly applied to "simplified" dilemmas. Case studies, while
      providing a context for engineering ethics, can encourage the premature analysis
      of specific moral conduct rather than the development of broad moral principles-
      stifling our students' facility with meta-ethics. Clearly, if a moral sense is
      developmental, ethics instruction should lead our students from lower to higher
      stages of moral development.

PMID- 15152846
TI  - Theoretical and methodological elements for integrating ethics as a foundation
      into the education of professional and design disciplines.
AB  - The paper addresses the integration of ethics into professional education related
      to the disciplines responsible for the conception and creation of the artificial
      (artefactual or technology). The ontological-epistemological paradigm of those
      disciplines is understood within the frame of the sciences of the artificial as
      established by Herbert Simon (1969). According to that paradigm, those sciences
      include disciplines not only related to the production of artefacts (technology),
      such as engineering, architecture, industrial design, etc, but also disciplines
      related to devised courses of action aimed at changing existing situations into
      preferred ones, like medicine, law, education, etc. They are centered on
      intentional action and at their core is the activity of design, which is their
      common foundation and attitude, or their common culture. The science of design
      becomes the broader foundational discipline for any professions engaged in the
      intentional transformation of the world. The main distinction between design
      disciplines and scientific ones rests on the object-project dichotomy. Indeed,
      contrary to Science that sees the world as an object to be observed, Design sees
      the world as a project and acts upon the world through projects, which are
      grounded in intentions, ends, and values. Design disciplines are meant to
      transform the world, or part of it, and are teleological. Being so, they are
      embodied in an act that is ethical and their ontology-epistemology must be
      addressed also through practical reason to resituate all professional disciplines
      according to their involved nature. The paper introduces theoretical,
      methodological, and ethical elements to establish a model that integrates ethics
      into the education of the professional disciplines, design-based disciplines,
      responsible for the creation of the artificial, artefactual or technological,
      world. The model is articulated around the notions of ethical engagement and
      responsibility through the act of design understood as action with intention
      situated in a project, common in all professional disciplines.

PMID- 15152847
TI  - A psychological model that integrates ethics in engineering education.
AB  - Ethics has become an increasingly important issue within engineering as the
      profession has become progressively more complex. The need to integrate ethics
      into an engineering curriculum is well documented, as education does not often
      sufficiently prepare engineers for the ethical conflicts they experience. Recent
      research indicates that there is great diversity in the way institutions approach
      the problem of teaching ethics to undergraduate engineering students; some
      schools require students to take general ethics courses from philosophical or
      religious perspectives, while others integrate ethics in existing engineering
      courses. The purpose of this paper is to propose a method to implement the
      integration of ethics in engineering education that is pedagogically based on
      Kohlberg's stage theory of moral development.

PMID- 15152848
TI  - American pragmatism as a guide for professional ethical conduct for engineers.
AB  - The ethical choices faced by engineers today are increasingly complex. Competing
      and conflicting ethical demands from clients, communities, employees, and
      personal objectives combine to suggest that engineers employ ethical approaches
      that are adaptive yet grounded in three concrete professional circumstances:
      first, that engineers apply unique professional skills in the service of a
      client, subject to protecting the public interest; second, that engineers advance
      the state of knowledge of their professional field through reflection, research,
      and sharing experience in journals and conferences, and third, that they develop
      new professionals by active mentoring. This paper examines five features of
      American pragmatism and suggests that its emphasis on specific, context-based
      ethical decision making can assist engineers in a postmodern setting. In
      particular, it considers the venues of interpersonal ethical choices,
      institutional ethical conflicts, and social choices that have ethical components.
      Pragmatism suggests that in such a complex ethical climate, there is a need for
      the co-evolution of judgment and action, for individual reflective judgment in
      particular situations, and for ceasing to search for a single, immutable
      principle for ethical choice.

PMID- 15152849
TI  - Eight-dimensional methodology for innovative thinking about the case and ethics
      of the Mount Graham, Large Binocular Telescope project.
AB  - This paper introduces the Eight Dimensional Methodology for Innovative Thinking
      (the Eight Dimensional Methodology), for innovative problem solving, as a unified
      approach to case analysis that builds on comprehensive problem solving knowledge
      from industry, business, marketing, math, science, engineering, technology, arts,
      and daily life. It is designed to stimulate innovation by quickly generating
      unique "out of the box" unexpected and high quality solutions. It gives new
      insights and thinking strategies to solve everyday problems faced in the
      workplace, by helping decision makers to see otherwise obscure alternatives and
      solutions. Daniel Raviv, the engineer who developed the Eight Dimensional
      Methodology, and paper co-author, technology ethicist Rosalyn Berne, suggest that
      this tool can be especially useful in identifying solutions and alternatives for
      particular problems of engineering, and for the ethical challenges which arise
      with them. First, the Eight Dimensional Methodology helps to elucidate how what
      may appear to be a basic engineering problem also has ethical dimensions. In
      addition, it offers to the engineer a methodology for penetrating and seeing new
      dimensions of those problems. To demonstrate the effectiveness of the Eight
      Dimensional Methodology as an analytical tool for thinking about ethical
      challenges to engineering, the paper presents the case of the construction of the
      Large Binocular Telescope (LBT) on Mount Graham in Arizona. Analysis of the case
      offers to decision makers the use of the Eight Dimensional Methodology in
      considering alternative solutions for how they can proceed in their goals of
      exploring space. It then follows that same process through the second stage of
      exploring the ethics of each of those different solutions. The LBT project pools
      resources from an international partnership of universities and research
      institutes for the construction and maintenance of a highly sophisticated,
      powerful new telescope. It will soon mark the erection of the world's largest and
      most powerful optical telescope, designed to see fine detail otherwise visible
      only from space. It also represents a controversial engineering project that is
      being undertaken on land considered to be sacred by the local, native Apache
      people. As presented, the case features the University of Virginia, and its
      challenges in consideration of whether and how to join the LBT project
      consortium.

PMID- 15152850
TI  - A Baldrige Process for ethics?
AB  - In this paper we describe and explore a management tool called the Caux Round
      Table Self-Assessment and Improvement Process (SAIP). Based upon the Caux Round
      Table Principles for Business--a stakeholder-based, transcultural statement of
      business values--the SAIP assists executives with the task of shaping their
      firm's conscience through an organizational self-appraisal process. This process
      is modeled after the self-assessment methodology pioneered by the Malcolm
      Baldrige National Quality Award Program. After briefly describing the SAIP, we
      address three topics. First, we examine similarities and differences between the
      Baldrige approach to corporate self-assessment and the self-assessment process
      utilized within the SAIP. Second, we report initial findings from two beta tests
      of the tool. These illustrate both the SAIP's ability to help organizations
      strengthen their commitment to ethically responsible conduct, and some of the
      tool's limitations. Third, we briefly analyze various dimensions of the business
      scandals of 2001-2002 (Enron, WorldCom, Tyco, etc.) in light of the ethical
      requirements articulated with the SAIP. This analysis suggests that the SAIP can
      help link the current concerns of stakeholders--for example, investors and the
      general public--to organizational practice, by providing companies with a
      practical way to incorporate critical lessons from these unfortunate events.

PMID- 15152851
TI  - Establishing ethics in an organization by using principles.
AB  - Laws, codes, and rules are essential for any community, public or private, to
      operate in an orderly and productive fashion. Without laws and codes, anarchy and
      chaos abound and the purpose and role of the organization is lost. However,
      danger is significant, and damage serious and far-reaching when individuals or
      organizations become so focused on rules, laws, and specifications that basic
      principles are ignored. This paper discusses the purpose of laws, rules, and
      codes, to help understand basic principles. With such an understanding an
      increase in the level of ethical and moral behavior can be obtained without
      imposing detailed rules.

PMID- 15152852
TI  - Institutional culture and individual behavior: creating an ethical environment.
AB  - Much of the work in professional ethics sees ethical problems as resulting from
      ethical ignorance, ethical failure or evil intent. While this approach gets at
      real and valid concerns, it does not capture the whole story because it does not
      take into account the underlying professional or institutional culture in which
      moral decision making is imbedded. My argument in this paper is that this culture
      plays a powerful and sometimes determinant role in establishing the nature of the
      ethical debate, i.e., it helps to define what are viable action options, what is
      the organization's genuine mission, and what behaviors will be rewarded or
      criticized. Given these conclusions, I also argue that consulting ethicists need
      more than an understanding of ethics theory, concepts and principles; they also
      need a sufficiently rich understanding of organizational culture and a
      willingness and an ability to critique that culture.

PMID- 15152853
TI  - Ethics in competitive bidding and contracting.

PMID- 15152854
TI  - Identification of shareholder ethics and responsibilities in online reverse
      auctions for construction projects.
AB  - The increasing number of companies providing internet services and auction tools
      helped popularize the online reverse auction trend for purchasing commodities and
      services in the last decade. As a result, a number of owners, both public and
      private, accepted the online reverse auctions as the bidding technique for their
      construction projects. Owners, while trying to minimize their costs for
      construction projects, are also required to address their ethical
      responsibilities to the shareholders. In the case of online reverse auctions for
      construction projects, the ethical issues involved in the bidding technique
      directly reflects on the owner's ethical and social responsibilities to their
      shareholders. The goal of this paper is to identify the shareholder ethics and
      responsibilities in online reverse auctions for construction projects by
      analyzing the ethical issues for the parties involved in the process. The
      identification of the ethical issues and responsibilities requires clear
      definition and understanding of professional ethics and the roles of the involved
      parties. In this paper, first, the concept of professional ethics and social
      responsibility is described in a general form. To illustrate the ethical issues
      and responsibilities, a sample case of bidding for a construction project using
      online reverse auction techniques is presented in which the shareholders were
      actively involved in questioning the ethical issues. The issues involved in the
      bidding process and their reflection on the shareholder responsibilities are
      described and analyzed for each stage of the process. A brief discussion of the
      overall process is also included to address the general ethical issues involved
      in online reverse auctions.

PMID- 15152855
TI  - Ethics in construction project briefing.
AB  - The research reported in this paper set out to investigate ethics in the initial
      stages of construction projects. Briefing is the first real contact stage between
      the commissioner (client/employer) of a project--at this stage a potential
      project--and those involved in project realization--the designers and,
      subsequently, the constructors. It is well known that early decisions are of
      greatest impact and so, the importance of the initial contacts, communications
      and consequent decisions are paramount. Different project participants are known
      to pursue individual objectives to varying degrees as well as possessing
      different perspectives and perceptions and operating/behaving in different ways.
      Hence, determination of the appropriate form, content etc. of a project is,
      inevitably, a matter of exercising value judgements and compromises and so,
      involves ethical considerations. A case study of a project through the briefing
      stage is reported and analysed, from initial contacts to scheme approval. It is
      apparent that a number of ethical concerns are manifest through the various
      actions of the major participants.

PMID- 15152856
TI  - Evil intent and design responsibility.
AB  - Mass casualty attacks in recent years have demonstrated the need to include "evil
      intent" as a design consideration. Three recent actual or potential weapons of
      mass destruction (WMD) attacks did not involve nuclear bombs or other devices
      designed as weapons, but rather benign objects used with evil intent. Just as
      unplanned events such as hurricanes, earthquakes, fires, and user misuse have
      been codified into design requirements based on the likelihood and potential
      impact of the event, "evil intent" has to become part of the design process for
      buildings, vehicles, equipment, and other items. The endstate should be
      reasonable additions to existing codes and standards such that it is clear what
      is and is not designed for. In the absence of specific design guidance,
      professionals with appropriate expertise can assess potential for "evil intent"
      and provide recommendations to design out or warn against this potential harm to
      public safety, particularly when codified requirements are not present.

PMID- 15152858
TI  - Ethics education in the consulting engineering environment: where do we start?
AB  - As a result of in-house discussions stimulated by previous Gonzaga engineering
      ethics conferences, Coffman Engineers began the implementation of what is to be a
      company-wide ethics training program. While preparing a curriculum aimed at
      consulting engineers, we found very little guidance as to how to proceed with
      most available literature being oriented towards the academic environment. We
      consulted a number of resources that address the teaching of engineering ethics
      in higher education, but questioned their applicability for the Consulting
      Engineering environment. This lack of guidance led us to informal research into
      the ethical knowledge and attitudes of both consulting engineers and engineering
      students. Some of our findings were unexpected, and suggest that a simpler
      approach to teaching ethics to working professionals might be preferred to that
      typically promoted in higher education.

PMID- 15152857
TI  - Does academic dishonesty relate to unethical behavior in professional practice?
      An exploratory study.
AB  - Previous research indicates that students in engineering self-report cheating in
      college at higher rates than those in most other disciplines. Prior work also
      suggests that participation in one deviant behavior is a reasonable predictor of
      future deviant behavior. This combination of factors leads to a situation where
      engineering students who frequently participate in academic dishonesty are more
      likely to make unethical decisions in professional practice. To investigate this
      scenario, we propose the hypotheses that (1) there are similarities in the
      decision-making processes used by engineering students when considering whether
      or not to participate in academic and professional dishonesty, and (2) prior
      academic dishonesty by engineering students is an indicator of future decisions
      to act dishonestly. Our sample consisted of undergraduate engineering students
      from two technically-oriented private universities. As a group, the sample
      reported working full-time an average of six months per year as professionals in
      addition to attending classes during the remaining six months. This combination
      of both academic and professional experience provides a sample of students who
      are experienced in both settings. Responses to open-ended questions on an
      exploratory survey indicate that students identify common themes in describing
      both temptations to cheat or to violate workplace policies and factors which
      caused them to hesitate in acting unethically, thus supporting our first
      hypothesis and laying the foundation for future surveys having forced-choice
      responses. As indicated by the responses to forced-choice questions for the
      engineering students surveyed, there is a relationship between self-reported
      rates of cheating in high school and decisions to cheat in college and to violate
      workplace policies; supporting our second hypothesis. Thus, this exploratory
      study demonstrates connections between decision-making about both academic and
      professional dishonesty. If better understood, these connections could lead to
      practical approaches for encouraging ethical behavior in the academic setting,
      which might then influence future ethical decision-making in workplace settings.

PMID- 15152859
TI  - Teaching business ethics to professional engineers.
AB  - Without question "business ethics" is one of the hot topics of the day. Over the
      past months we have seen business after business charged with improper practices
      that violate commonly-accepted ethical norms. This has led to a loss of
      confidence in corporate management, and has had severe economic consequences.
      From many quarters business educators have heard the call to put more emphasis on
      ethical practices in their business courses and curricula. Engineering educators
      are also heeding this call, since the practice of engineering usually involves
      working for (or leading) a business and/or engaging in business transactions. In
      the summer of 2002, Auburn University's Engineering Professional Development
      program made the decision to produce--based on the author's Executive MBA course
      in Business Ethics--a distance-delivered continuing education program for
      professional engineers and surveyors. Participants across the USA now may use the
      course to satisfy continuing education requirements with respect to professional
      licensing and certification. This paper outlines the purpose and content of the
      course and describes its production, distribution, application, and evaluation.

PMID- 15152860
TI  - The dilemma of ethics in engineering education.
AB  - This paper briefly summarizes current thinking in engineering ethics education,
      argues that much of that ethical instruction runs the risk of being only
      superficially effective, and explores some of the underlying systemic barriers
      within academia that contribute to this result. This is not to criticize or
      discourage efforts to improve ethics instruction. Rather it is to point to some
      more fundamental problems that still must be addressed in order to realize the
      full potential of enhanced ethics instruction. Issues discussed will include:
      intellectual engagement versus emotional engagement; the gravitational pull of
      curricular structures; the nature of engineering faculty; and the "engineer
      ization" of ethics.

PMID- 15152861
TI  - Ethics training: a genuine dilemma for engineering educators.
AB  - This is an examination of three main strategies used by engineering educators to
      integrate ethics into the engineering curriculum. They are: (1) the standalone
      course, (2) the ethics imperative mandating ethics content for all engineering
      courses, and (3) outsourcing ethics instruction to an external expert. The
      expectations from each approach are discussed and their main limitations
      described. These limitations include the insular status of the stand-alone
      course, the diffuse and uneven integration with the ethics imperative, and the
      orphaned status of ethics using the outside expert. A fourth option is proposed-
      a special modular option. This strategy avoids the limitations of earlier
      approaches and harmonizes well with curricular objectives and professional
      values. While some help is provided by a professional ethicist, the headliner for
      the series of seminars is a high-profile engineer who shares an ethics dilemma
      encountered in professional practice. Students discuss the case and propose
      solutions. The goal is to make ethics applicable to real-life problems facing
      working engineers and to help change behaviors.

PMID- 15152862
TI  - Teaching engineering ethics to first-year college students.
AB  - One of the methods used at Penn State to teach engineering students about ethics
      is a one-credit First-Year Seminar entitled "How Good Engineers Solve Tough
      Problems." Students meet in class once a week to understand ethical frameworks,
      develop ethical problem-solving skills, and to better understand the professional
      responsibilities of engineers. Emphasis is on the ubiquity of ethical problems in
      professional engineering. A learning objective is the development of moral
      imagination, similar to the development of technical imagination in engineering
      design courses. Making sound arguments is also addressed in the process of
      reasoning through cases, and critiquing other's arguments. Over the course of the
      semester, students solve five engineering ethics cases. Each week, a student team
      of four people is responsible for reading the assigned section of the text,
      developing a summary, and leading the class discussion.

PMID- 15152863
TI  - Esssential ethics--embedding ethics into an engineering curriculum.
AB  - Ethical decision-making is essential to professionalism in engineering. For that
      reason, ethics is a required topic in an ABET approved engineering curriculum and
      it must be a foundational strand that runs throughout the entire curriculum. In
      this paper the curriculum approach that is under development at the Padnos School
      of Engineering (PSE) at Grand Valley State University will be described. The
      design of this program draws heavily from the successful approach used at the
      service academies--in particular West Point and the United States Naval Academy.
      As is the case for the service academies, all students are introduced to the
      "Honor Concept" (which includes an Honor Code) as freshmen. As an element of
      professionalism the PSE program requires 1500 hours of co-op experience which is
      normally divided into three semesters of full-time work alternated with academic
      semesters during the last two years of the program. This offers the faculty an
      opportunity to teach ethics as a natural aspect of professionalism through the
      academic requirements for co-op. In addition to required elements throughout the
      program, the students are offered opportunities to participate in service
      projects which highlight responsible citizenship. These elements and other parts
      of the approach will be described.

PMID- 15152864
TI  - Student development and ownership of ethical and professional standards.
AB  - Ethics and professional conduct are vital to civil engineering undergraduate
      curricula. Many programs struggle to ensure that students are given an adequate
      exposure to and appreciation of ethical and professional conduct issues. This
      paper describes a two-part ethics/professionalism project used in a senior-level
      course taught at the University of Arkansas. Initially, students scrutinize
      ethical canons and standards of professional conduct published by the American
      Society of Civil Engineers (ASCE) and the National Society of Professional
      Engineers (NSPE), and prepare an essay concerning the applicability of these
      standards. The second part of the project builds on the first: based on the
      opinion(s) generated in Part 1, students are asked to develop a set of canons or
      standards targeted specifically to the undergraduate student, and suggest
      processes for implementing those standards within the department. Project
      objectives include: (1) exposure to nationally-recognized ethical canons and
      standards of professional conduct; (2) personal formulation of ethical and
      professional standards; (3) skill enhancement for non-technical written
      communications. Feedback by students prior to and after the project indicates
      success in meeting all objectives. The feedback also indicates that for some
      students, definitions and applications of ethics and professionalism are being
      broadened to include more than academic honesty issues.

PMID- 15152865
TI  - Effectiveness of an ethics course delivered in traditional and non-traditional
      formats.
AB  - This paper details a three-credit-hour undergraduate ethics course that was
      delivered using traditional, distance, and compressed formats. OLS 263: Ethical
      Decisions in Leadership is a 200-level course offered by the Department of
      Organizational Leadership and Supervision in the Purdue School of Engineering and
      Technology at Indiana University Purdue University Indianapolis (IUPUI). Students
      in engineering, technology, business, nursing, and other majors take the course.
      In an effort to determine student perceptions of course and instructor
      effectiveness, end-of-course student survey data were compared using data from
      traditional, distance, and compressed sections of the course. In addition,
      learning outcomes from the final course project were evaluated using a
      standardized assessment rubric and scores on the course project.

PMID- 15152866
TI  - A professional ethics learning module for use in co-operative education.
AB  - The Professional Practice Program, also known as the co-operative education (co
      op) program, at the University of Cincinnati (UC) is designed to provide eligible
      students with the most comprehensive and professional preparation available.
      Beginning with the Class of 2006, students in UC's Centennial Co-op Class will be
      following a new co-op curriculum centered around a set of learning outcomes
      Regardless of their particular discipline, students will pursue common learning
      outcomes by participating in the Professional Practice Program, which will cover
      issues of organizational culture, technology, professional ethics, and the
      integration of theory and practice. During their third co-op work term, students
      will complete a learning module on Professional Ethics. To complete the learning
      module students must familiarize themselves with the code of ethics for their
      profession, create a hypothetical scenario portraying an ethical dilemma that
      involves issues covered by the code, resolve the dilemma, and explain why their
      resolution is the best course of action based upon the code of ethics. A three
      party assessment process including students, employers and faculty complete the
      module.

PMID- 15152867
TI  - Senior capstone design and ethics: a bridge to the professional world.
AB  - A senior level capstone design experience has been developed and offered with a
      particular emphasis on many of the professional issues raised in Accreditation
      Board for Engineering and Technology (ABET) Engineering Criterion IV. The course
      has sought to develop student awareness of the ethical foundation of the
      engineering profession, the global and societal framework within which engineers
      practice, and the environmental impact on engineering. The capstone design course
      also focused upon improving the technical communications skills of the graduating
      senior class with both extensive instruction in writing and multiple workshops
      dealing with the art of making an effective oral presentation. The effectiveness
      of the design course was assessed using Kirkpatrick's model for evaluating
      training programs.

PMID- 15152868
TI  - Incorporating environmental ethics into the undergraduate engineering curriculum.
AB  - The design and economic realities associated with Personal Computers (PCs) was
      used as a model for implementing ethical issues into the core-engineering
      curriculum. Historically, products have not been designed to be recycled easily.
      By incorporating environmental ethics into our classrooms and industries,
      valuable materials can be recovered and harmful materials can be eliminated from
      our waste stream. Future engineers must consider the economic cost-benefit
      analysis of designing a product for easy material recovery and recycling versus
      the true cost of the disposal and continued use of virgin materials. A three hour
      unit on the economic and environmental impacts of product design is proposed for
      inclusion in the ABET accredited engineering program.

PMID- 15152869
TI  - Sustainable and responsible design from a Christian worldview.
AB  - Many aspects of design require engineers to make choices based on non
      quantifiable personal perspectives. These decisions touch issues in aesthetics,
      ethics, social impact, and responsibility and sustainability. Part of Baylor
      University's mission is to provide a learning community in which Christian life
      values and worldviews might be integrated into academic disciplines. In view of
      this institutional commitment, members of the Engineering faculty are
      investigating how Christian worldviews might interact with elements of
      engineering design in such a way as to produce uniquely Christian insights and
      inform the non-quantifiable aspects of the engineering process.

PMID- 15152870
TI  - Inflammation and the pathogenesis of inverted papilloma.
AB  - BACKGROUND: Despite existing clinical and histopathological evidence, the role of
      inflammation in the pathogenesis of inverted papilloma (IP) is not well
      understood The goal of this study was to describe the inflammatory cell component
      present in sinonasal papilloma (SP), with the intention of further defining the
      existence of inflammation in IP and perhaps gaining insight into IP
      pathophysiology. METHODS: Computerized database analysis was performed to
      identify all patients with SP who underwent surgery at the Cleveland Clinic
      Foundation between 1995 and 2001. Histopathological features of all SP were
      reviewed and semiquantitative analysis of the inflammatory cells present was
      performed. IP was histopathologically graded into four categories by the extent
      of inflammatory infiltrate and cellular atypia. Statistical analysis of the
      inflammatory cell component present in the epithelial layer of exophytic
      papilloma and IP was performed. RESULTS: SP was classified into three types:
      cylindrical papilloma (5% [2/41]), exophytic squamous papilloma (34% [14/ 41]),
      and IP (61% [25/41]). Twenty-eight instances of IP in 25 patients were
      identified. Altogether, 11% were grade I (3/28), 54% were grade II (15/28), 25%
      were grade III (7/28), and 11% were grade IV (3/28). The inflammatory cell
      population was significantly greater in IP compared with other SPs and greater in
      grades I and II IP when compared with grade III and IV IP. CONCLUSION:
      Inflammatory cells were identified as a significant cell population in IP,
      whereas it was less commonly encountered in other forms of SP. The proposed IP
      staging system may serve as the foundation for improved understanding of IP and,
      ultimately, may help to predict recurrence or apparent malignant transformation.

PMID- 15152871
TI  - Invasive fungal sinusitis: a 15-year review from a single institution.
AB  - BACKGROUND: The aim of this study was to review our experience with patients with
      invasive fungal sinusitis (IFS) to determine outcomes and identify factors that
      may affect patient survival. METHODS: A retrospective review was performed.
      RESULTS: Forty-three patients were identified accounting for 45 cases of IFS. The
      underlying reasons for immunosuppression were hematologic malignancy (28
      patients), diabetes mellitus (10 patients), solid organ transplant (3 patients),
      chronic steroid use (3 patients), and acquired immunodeficiency syndrome (1
      patient). Eight of 45 cases (18%) died of IFS. Of the 28 cases associated with
      hematologic malignanancy, 3 patients died of IFS (11%) and 4 patients (14%) died
      of other causes with persistent IFS. None of these 7 patients had recovery of
      their absolute neutrophil count, and all patients who recovered from IFS
      recovered to a normal absolute neutrophil count. Four of 10 (40%) diabetic
      patients died of IFS, and 66% of survivors had persistent neurological or visual
      morbidity. The imortality rate was 29% for patients infected with Mucor and 11%
      for patients injected with Aspergillus. CONCLUSION: We have found the overall
      mortality rate directly related to IFS to be 18%. The rate is higher for diabetic
      patients than for patients with hematologic causes for their immunosuppression.
      This is likely because of the higher index of suspicion and early diagnosis and
      treatment of patients with neutropenia and a less-fulminant, slower-progressing
      form of IFS from Aspergillus, apparently a less virulent fungus than Mucor.
      Intracranial involvement and failure to recover from neutropenia are the factors
      that led to poor prognosis in this series.

PMID- 15152872
TI  - Management of the lateral frontal sinus lesion and the supraorbital cell
      mucocele.
AB  - BACKGROUND: Masses that radiographically appear in the lateral aspect of the
      frontal sinus can be difficult to access and often are approached through
      external approaches. Supraorbital ethmoid cells pneumatize the orbital plate of
      the ethmoid bone to lie posterior and lateral to the frontal sinus. Opacification
      of a supraorbital cell may radiographically give the appearance of a laterally
      based frontal sinus lesion. Often, these represent mucoceles, in which their
      drainage can be achieved through endoscopic techniques and without the need for
      an external approach. METHODS: Retrospective review of patients treated for
      lateral frontal sinus lesions at a tertiary sinus center was performed.
      Radiology, endoscopic findings, operative reports, and patient symptoms were
      reviewed. RESULTS: Ten patients were identified with lateral frontal sinus
      lesions based on radiography of the paranasal sinuses and nasal endoscopy. All
      patients were determined to be supraorbital mucoceles. These patients underwent
      surgical drainage using computer-aided endoscopic techniques. Initially,
      endoscopic drainage of the mucocele was successful in all patients. One patient
      was lost to follow-up after 3 months and one patient underwent a revision
      endoscopic surgery with trephination 5 months after the initial drainage. The
      remaining eight patients remain free of disease by nasal endoscopy and
      postoperative computed tomography scans (median follow-up of 25 months; range, 8
      38 months). CONCLUSION: Knowledge of the anatomy of the ethmoid complex and
      presence of various cells within the frontal recess such as supraorbital cells
      are important in the management of the laterally based frontal sinus lesion.
      Often, these lesions may represent supraorbital cell mucoceles amenable to
      endoscopic drainage. Given the nature of mucoceles, long-term follow-up is needed
      before endoscopic drainage of these lesions can be validated. However,
      preliminary data suggest that an endoscopic approach provides for adequate
      drainage and helps avoid external approaches.

PMID- 15152873
TI  - Learning curves, acquisition, and retention of skills trained with the endoscopic
      sinus surgery simulator.
AB  - BACKGROUND: As an initial step in evaluating the effectiveness of training
      otolaryngology residents on an endoscopic sinus surgery simulator (ES3), we have
      assessed the ability of the ES3 to train persons inexperienced in sinus surgery
      (medical students) to perform certain simulated procedural tasks needed in
      endoscopic sinus surgery (ESS). METHODS: A total of 26 medical students were
      enrolled and trained on the ES3 following a preset protocol in the three levels
      of difficulty and complexity (novice, intermediate, and advanced modes). RESULTS:
      In the novice mode (three-dimensional abstract images are used to teach the use
      of endoscopic surgical equipment), medical students displayed a steep learning
      curve within three to five trials on the simulator and after an additional four
      to five trials, they reached a plateau in their learning curves to within 90% of
      that of experienced sinus surgeons. In the intermediate mode (ESS is performed on
      a simulated patient with teaching aids), medical students were able to reach a
      plateau in their learning curves to within 80% of that of experienced surgeons.
      This performance was sustained in the advanced mode (simulated sinus surgery
      without teaching aids). We observed that medical students, who had novice or
      intermediate mode training interrupted with an interval of 11-60 days, were able
      to resume their training without deviation from their prior learning curves.
      CONCLUSION: Intensive, proctored training on the ES3 can train inexperienced
      persons to perform simulated ESS within a reasonable approximation of the
      performance of experienced sinus surgeons on the ES3 and the training that an
      inexperienced person receives on the simulator is not short term but is retained
      over a period of at least 2 months.

PMID- 15152874
TI  - Myeloperoxidase in nasal secretion as a cell-activation marker in acute
      sinusitis.
AB  - BACKGROUND: Acute bacterial infections of the upper respiratory tract, including
      the nasal sinuses, lead to an activation of neutrophil granulocytes. The protein
      myeloperoxidase (MPO) is released by this cell type only and therefore can act as
      a marker for activity of inflammation. METHODS: In a prospective multicenter
      study, 45 patients with acute bacterial sinusitis (diagnosed by clinical
      examination, ultrasonography, and X ray or computed tomography scan) were treated
      with two different antibiotics (Cefditoren or Cefuroxim twice a day for 10 days).
      Nasal secretions were collected with absorbing foam-rubber samplers and a
      concentration of MPO was evaluated before the therapy and after 7 +/- 1 days and
      14 +/- 2 days of antibiotic treatment. The concentrations of MPO were measured by
      a radioimmunoassay method and the dilution factors were determined by the lithium
      method. RESULTS: Significant differences in the MPO concentration in nasal
      secretions between the first and third visit could be found in both groups (p <
      0.01 each). No significant difference was seen within the two different
      antibiotics used. CONCLUSION: Measurement of MPO concentration in nasal
      secretions showed a significant change after antibiotic treatment of acute
      bacterial rhinosinusitis. The reduction of MPO levels correlated with the
      observed clinical and radiological improvement of the disease. Additional
      investigations are needed to achieve more knowledge about basal concentrations of
      MPO in healthy persons and different activation patterns before it can be
      determined whether the MPO measurement could be a suitable method for monitoring
      the success of an antibiotic treatment in acute bacterial sinusitis.

PMID- 15152875
TI  - An endoscopic study of the greater palatine nerve.
AB  - BACKGROUND: Using an endoscopic approach, lateral sphenoid air cells and terminal
      branches of the internal maxillary artery often can be accessed through the
      pterygomaxillary fossa: however, injury to the greater palatine nerve (GPN) can
      occur if the anatomy of this region is not understood clearly. This study was
      undertaken to define the pathway of the GPN and to identify landmarks useful in
      preventing its injury. METHODS: Six cadaveric heads were used to endoscopically
      dissect and examine 11 pterygomaxillary fossae. An additional latex-injected
      cadaveric head was sectioned coronally and dissected bilaterally. The
      relationships between the vascular, neurological and bony structures and foramena
      were noted and described. RESULTS: All specimens studied maintained consistent
      relationships. The sphenopalatine and posterior nasal arteries cross nearly
      perpendicular and just superficial to the GPN. The GPN traveled anteriorly and
      inferiorly to reach the greater palatine foramen. The lateral wall of the canal
      ranged from a thin bony covering to complete dehiscence and was thinnest as it
      crossed the inferior turbinate and approached the foramen. The foramen rotundum
      was located lateral and superior to the sphenopalatine foramen near the roof of
      the maxillary sinus. CONCLUSION: When surgically approaching the pterygomaxillary
      fossa, injury to the GPN is avoidable by thorough knowledge of anatomy and
      awareness of the described landmarks.

PMID- 15152876
TI  - Propagation of human nasal chondrocytes in microcarrier spinner culture.
AB  - OBJECTIVE: The aim of this study was to test the effectiveness of nasal septal
      chondrocytes, propagated in microcarrier spinner culture, as an alternative
      tissue source of chondrocytic cells for cartilage grafts for head and neck
      surgery and for articular cartilage repair. METHODS: We harvested chondrocytes
      from 159 patients, ranging in age from 15 to 80 years and undergoing repair of a
      deviated nasal septum, and propagated the cells in a microcarrier spinner culture
      system. The nasal chondrocytes proliferated and produced extracellular matrix
      components similar to that produced by articular chondrocytes. RESULTS: In
      microcarrier spinner culture on collagen beads, chondrocyte numbers increased up
      to 14-fold in 2 weeks. After a month, the microcarriers seeded with nasal
      chondrocytes began to aggregate, producing a dense cartilage-like material. The
      newly synthesized extracellular matrix was rich in high molecular weight
      proteoglycans, and the chondrocytes expressed type II collagen and aggrecan but
      not type I collagen. CONCLUSION: These studies support the feasibility of
      engineering cartilage tissue using chondrocytes harvested from the nasal septum.
      Injectable and solid formulations based on this technology are being evaluated
      for applications in craniomaxillofacial reconstructive surgery and for plastic
      and orthopedic surgery practices.

PMID- 15152877
TI  - Acute effects of 1,1,1-trichloroethane on human olfactory functioning.
AB  - BACKGROUND: Animal experiments indicate that 1,1,1-trichloroethane can cause
      degeneration of the olfactory epithelium. The effects of 1,1,1-trichloroethane on
      human odor perception still have not been investigated. The goal of this study
      was to learn more about acute effects of 1,1,1-trichloroethane. METHODS: Twelve
      healthy, nonsmoking students were exposed to 200 and 20 ppm (control) 1,1,1
      trichloroethane in an exposure chamber for 4 hours according to a crossover
      design. Olfactory functioning was investigated with the Sniffin' Sticks. The test
      includes the determination of the detection threshold for n-butanol and an odor
      identification test. RESULTS: After 1 hour of exposure to 200 ppm 1,1,1
      trichloroethane, no effects on olfactory functioning were observed. After 4
      hours, the olfactory threshold for n-butanol was slightly (p = 0.04) elevated.
      CONCLUSION: The threshold shift may be caused by different mechanisms, including
      inflammation of the olfactory mucosa or degeneration of receptor cells.

PMID- 15152878
TI  - A preliminary report on the effects of paclitaxel-impregnated stents on sheep
      nasal mucosa.
AB  - INTRODUCTION: Traditional frontal sinus stents serve only as mechanical devices.
      It has been proposed that stents also may serve as drug-delivery systems for the
      topical application of drugs that minimize postoperative scarring. Paclitaxel
      (Taxol), which has recognized antiscarring effects, may be incorporated via a
      polymeric formulation into standard rubber stents. The impact of topically
      applied paclitaxel on the morphology of the nasal mucosa is unknown. METHODS: An
      adult sheep model was used for this study. A modified rubber T-tube stent
      (incorporating paclitaxel at varying dosages) was secured to each side of the
      septum in four animals (eight sides). An unmodified T-tube was placed on each
      side of one animal, a T-tube with the drug carrier (but no paclitaxel) was placed
      on each side of the second animal, and T-tubes with varying paclitaxel were
      placed on each side of the final two animals. After 4 weeks, animals were killed
      and the nasal mucosa was harvested. The nasal mucosa was sectioned and stained
      with hematoxylin and eosin. A pathologist then assessed the nasal mucosa for
      vascular congestion, glandular atrophy, chronic inflammation, mucosal metaplasia,
      and mucosal ulceration. RESULTS: No consistent histopathological differences were
      noted in the specimens. All specimens showed varying degrees of vascular
      congestion, glandular atrophy, chronic inflammation, and mucosal metaplasia; the
      paclitaxel-impregnated stents were not consistently associated with more severe
      mucosal injury. Finally, mucosal ulceration was noted to be very rare in all
      specimens. CONCLUSION: This preliminary report describes the impact of paclitaxel
      impregnated stents on sheep nasal mucosa, which tolerated these stents very well.
      Because paclitaxel minimizes scarring reactions at very low concentrations,
      paclitaxel-impregnated stents may prove useful in clinical situations in which
      frontal sinus stenting is deemed necessary. Additional investigations with animal
      models, as well as clinical trials, may be warranted.

PMID- 15152879
TI  - Endoscopic sinus surgery in geriatric population.
AB  - BACKGROUND: With the baby boomers getting older, endoscopic sinus surgery (ESS)
      is being performed more on elderly people than before. We compared patients
      undergoing ESS who were >65 years of age with those <65 years. MATERIALS AND
      METHODS: We reviewed our database of cases who had ESS between 1992 and 2002.
      Demographics and patient characteristics and complications encountered
      intraoperatively and immediately postoperatively were reviewed. RESULTS: Forty
      six (8.1%) patients were older than 65 years of age compared with 522 patients
      who were 18-64 years old. The older group had a 24% revision rate compared with
      34% in the younger group. Complication rates were 21.7% for the elderly compared
      with 12.8% for the younger group. There was a significantly higher complication
      rate in the older group of people who were having revision ESS. CONCLUSION: The
      elderly people who were having revision surgery had a higher risk for
      complications compared with those having primary surgery or those <65 years old.

PMID- 15152880
TI  - Responses to behaviorally vs culturally tailored cancer communication among
      African American women.
AB  - OBJECTIVE: To examine whether tailored cancer communication for African American
      women can be enhanced by tailoring on 4 sociocultural constructs: religiosity,
      collectivism, racial pride, and time orientation. METHODS: In a randomized trial,
      participants (n=1,227) received a women's health magazine tailored using
      behavioral construct tailoring (BCT), culturally relevant tailoring (CRT), or
      both (COMBINED). Two follow-up interviews assessed responses to the magazines.
      RESULTS: Responses to all magazines were positive. The health focus of the
      magazines was initially obscured in the CRT condition, but this disappeared over
      time, and CRT magazines were better liked. CONCLUSIONS: Implications for
      developing and understanding effects of tailored cancer communication are
      discussed.

PMID- 15152881
TI  - Family process and parent's leisure time physical activity.
AB  - OBJECTIVE: To examine relations between family environment and parent's leisure
      time physical activity conceived as a system of interdependent variables (LTPA
      specific variables) including family rules, support, and exercise activity.
      METHODS: Family environment was described using site of residence and a family
      typology. Two-way MANCOVA on the LTPA-specific scores were conducted for 533 male
      and 603 female parents from a community sample. RESULTS: Main effects for family
      type, site of residence, and a significant family type by site of residence
      interaction were found. There were gender-specific patterns of LTPA-specific
      scores. CONCLUSION: Different families may have different mechanisms of influence
      on physical activity habits.

PMID- 15152882
TI  - Telephone counseling for population-based smoking cessation.
AB  - OBJECTIVES: To examine the options for use, efficiency, and effectiveness for
      structuring a population-based telephone smoking-cessation service. METHODS:
      Callers (n=632) to a 1-800 number were randomized in a 2 (50-minute counseling
      with 2/6 calls) x 2 (pamphlet/booklet) design with print only control. RESULTS:
      Six-month use of the service was 0.6% of adult smokers. Service promotion cost
      31.02 dollars/person. Telephone counseling resulted in higher continued
      abstinence (5%) than did print only (1%), P<.05. Amount of print and calls did
      not increase cessation. Six calls resulted in lower completion rates than 2 (22%
      vs 56%, P<.05). CONCLUSIONS: For planning, consider 1% use, low-cost promotion,
      pamphlet, 50-minute initial counseling plus 2 follow-ups, and minimize call
      attempts.

PMID- 15152883
TI  - Obesity treatment: broadening our perspective.
AB  - OBJECTIVE: To selectively review the dietary literature to broaden perspectives
      on energy restriction as the primary determinant of successful obesity treatment.
      METHODS: Forty-five articles describing novel dietary behaviors and nutrient
      intakes that may impact obesity treatment are examined. RESULTS: Two areas of
      promising research were identified: (a) Dietary behaviors and patterns--eating
      frequency, meal timing, specific dietary pattern and (b) Nutritional factors-
      fat, fiber, glycemic load, carbohydrate. CONCLUSIONS: Caloric restriction leads
      to weight loss. However, promotion of dietary behaviors that focus primarily on
      cutting calories needs evaluation. There may be many dietary behaviors and
      patterns that promote weight loss and maintenance, making it essential to
      consider new nutritional approaches for obesity treatment.

PMID- 15152884
TI  - Risk factors for osteoporosis among middle-aged women.
AB  - OBJECTIVE: To investigate the risk factors for osteoporosis among a sample of
      middle-aged women. METHODS: Adipose tissue and bone mineral density levels at the
      left femur, lumbar spine, and total body were assessed using dual-energy x-ray
      absorptiometry (DXA). Subjects (n=342) were surveyed regarding a variety of
      osteoporosis-related risk factors. Forward stepwise multiple regression
      procedures were utilized. RESULTS: Menstrual status, hormone replacement therapy,
      adipose tissue, and dairy product intake were retained in the regression models.
      CONCLUSIONS: Osteoporosis prevention programs need to emphasize the importance of
      hormonal status and body composition in addition to obtaining adequate calcium
      intake.

PMID- 15152885
TI  - Breast cancer knowledge and beliefs in subpopulations of African American and
      Caribbean women.
AB  - OBJECTIVE: To examine breast cancer belief and knowledge deficits among
      previously unstudied African and Caribbean subpopulations and to consider the
      particular knowledge and belief components that are most lacking in each group.
      METHODS: 1,364 African American, US-born white, English-speaking Caribbean,
      Haitian, Dominican, and Eastern European women were recruiting via stratified
      cluster sampling. Participants provided demographics and measures of beliefs and
      knowledge. RESULTS: There were between-group differences in cancer knowledge and
      beliefs and within-group variation in terms of which particular knowledge and
      belief items varied. CONCLUSIONS: Studying how cognitive factors relate to
      screening in well-defined minority groups will capacitate interventions suited to
      the knowledge and belief deficits that characterize populations of diverse women.

PMID- 15152887
TI  - Minimal-contact physical activity interventions in women: a pilot study.
AB  - OBJECTIVE: To examine the impact of 3 minimal-contact lifestyle interventions on
      physical activity in women. METHODS: Fifty female volunteers were randomly
      assigned to one of 3 lifestyle physical activity interventions for 8 weeks.
      Subjects wore an accelerometer for a week at baseline and postintervention to
      objectively monitor their physical activity. RESULTS: Participants significantly
      increased their physical activity from baseline to postintervention; however,
      there was no significant difference in physical activity among the 3 intervention
      groups. CONCLUSIONS: Results of this pilot study support the use of minimal
      contact lifestyle interventions to promote physical activity in women.

PMID- 15152886
TI  - Parental monitoring and adolescent drinking: results of a 12-month follow-up.
AB  - OBJECTIVE: To examine the relationship between parental monitoring and adolescent
      drinking over time. METHODS: Adolescents completed a baseline survey regarding
      their involvement with alcohol and parental monitoring. They were interviewed 12
      months later, to obtain follow-up measures of drinking and involvement in alcohol
      risk situations. RESULTS: Highly monitored adolescents were less likely to report
      that they were drinking 12 months later. This relationship remained when
      controlling for age, gender, drinking at baseline, and being in various high-risk
      situations. CONCLUSIONS: The longer term protective relationship between parental
      monitoring and alcohol involvement was demonstrated. The need to establish
      frequent parental monitoring is indicated.

PMID- 15152888
TI  - Dextroamphetamine use during B-2 combat missions.
AB  - INTRODUCTION: Fatigue among warriors can jeopardize mission success. Prescribed
      stimulant medications, in-flight sleep, and self-medication with caffeine can
      mitigate fatigue. During Operation Iraqi Freedom, pilots flew the B-2 bomber to
      targets in Iraq from one of two airfields. Sortie durations were long (16.9 h)
      from one field and very long (35.3 h) from the other. Controversy exists
      concerning the use of stimulant medication, in part because of a paucity of
      combat data. METHODS: A retrospective analysis of 75 pilots who performed 94
      combat sorties was performed. We examined the prevalence of the pilot's decision
      to use dextroamphetamine, caffeine, and in-flight sleep during combat. We
      compared demographic factors, the impact of one anti-fatigue tool on the use of
      others, stimulant benefit, and adverse effects. RESULTS: Pilots on shorter
      missions used dextroamphetamine for 97% and in-flight naps for 13% of sorties.
      Those on longer missions used dextroamphetamine on 58% and naps on 94% of
      sorties. Stimulant use was not affected by pilot age, bomber experience, or long
      duration experience. The opportunity to obtain in-flight sleep was limited by
      certain mission profiles, which influenced the decision to use dextroamphetamine.
      Among pilots who used the medication, 97% noted a benefit. Side effects and
      failure to observe benefits were uncommon. CONCLUSIONS: B-2 pilots in long
      duration combat flight selectively employ dextroamphetamine, naps, and other
      fatigue countermeasures. Major determinants of these decisions are mission
      requirements and the pilot's experience with each measure and its effect.

PMID- 15152889
TI  - Morphometric changes in vagal nerves of fourth generation mice passage-bred in a
      2-G environment.
AB  - INTRODUCTION: Previous studies have shown that microgravity induces both
      functional and structural adaptations in the autonomic nerves. Functional
      adaptation to hypergravity has also been reported, but structural change has not
      yet been isolated. The purpose of this study was to evaluate structural
      adaptation to hypergravity in the parasympathetic nerve. METHOD: We selected
      fourth generation mice which were passage-bred in a 2-G environment by cycles of
      coupling, delivery, and growth. Complete left cervical vagal nerves of these mice
      were studied in transverse sections by electron microscopy. The number of small
      (diameter < 5 microm, thin and light-stained myelin sheath) and large (diameter >
      5 microm, thick and dark-stained myelin sheath) myelinated fibers was counted.
      RESULTS: The total number of all myelinated fibers (2 G: 795 +/- 103, 1 G: 644 +/
      60) and the number of small myelinated fibers (2 G: 657 +/- 95, 1 G: 522 +/- 66)
      were significantly greater in the 2-G mice than those in the 1-G mice (p < 0.05).
      The number of large myelinated fibers in the 2-G mice was greater than that in
      the 1-G mice, although it was not statistically significant (2 G: 138 +/- 15, 1
      G: 122 +/- 16; p = 0.091). DISCUSSION: The results show that the autonomic nerves
      can adapt structurally to hypergravity. We contend that the present results are
      due to the fact that the mice were passage-bred. As far as we know, this is the
      first report to show an increase in myelinated fibers in autonomic nerves under
      prolonged exposure to an increased G environment.

PMID- 15152891
TI  - Neoprene wet-suit hood affects low-frequency underwater hearing thresholds.
AB  - INTRODUCTION: Psychophysical measures of wet-suit hood sound attenuation are
      needed to provide the diving community with guidance on protection from
      underwater sound. METHODS: Underwater hearing thresholds were obtained from 15
      male and 5 female recreational divers with and without a 3-mm thick wet-suit
      hood. Dives were conducted at a depth of 1 m in a large quiet anechoic pool.
      Thresholds were determined using a two-interval forced-choice procedure with a
      0.71 probability of positive response at convergence. A 1-s pure tone was
      presented with a 20-ms rise and fall time at 100, 200, 250, 300, 400, and 500 Hz.
      RESULTS: Without a wet-suit hood, mean thresholds decreased from 99 dB re 1
      microPa at 100 Hz to 85 dB at 500 Hz. Thresholds were statistically similar at
      100 to 300 Hz with and without the wet-suit hood, but were significantly
      increased at 400 and 500 Hz with the hood (p < 0.001). CONCLUSIONS: In
      conclusion, at shallow depths, a 3-mm neoprene wet-suit hood attenuates
      underwater sound by approximately 10 dB for frequencies between 400 Hz and 500
      Hz. At frequencies below 400 Hz, a 3-mm neoprene wet-suit hood offers no sound
      protection.

PMID- 15152890
TI  - Heat strain attenuation while wearing NBC clothing: dry-ice vest compared to
      water spray.
AB  - BACKGROUND: While wearing impermeable nuclear, biological, and chemical (NBC)
      clothing, reduction of thermal stress is of primary importance. We compared the
      effect between two cooling methods on the attenuation of heat strain. METHODS:
      There were six male subjects who were divided into two groups of three and
      exposed on two consecutive days to 125 min of exercise in a high heat load (40
      degrees C, 40% RH) wearing NBC clothing. They were cooled by one of two different
      cooling methods: an active cooling vest (CV) based on the sublimation of dry ice,
      or tap water spraying (TP). RESULTS: After 2 h, rectal temperature (Tre) was
      significantly higher for the CV compared with the TP (38.1 +/- 0.04 degrees C vs.
      37.7 +/- 0.10 degrees C, respectively). Skin temperature (Tsk) was significantly
      higher for the CV compared with the TP (36.60 +/- 0.54 degrees C vs. 34.90 +/-
      0.35 degrees C, respectively). In the second hour, heart rate (HR) was
      significantly higher for CV compared with TP (118 +/- 13 bpm vs. 104 +/- 64 bpm,
      respectively). Heat storage was significantly higher after the first and second
      hours for the CV compared with the TP. The physiological strain index (PSI) was
      higher for CV compared with TP in the second hour. Sweat rate (msw) was
      significantly higher for CV compared with TP (560 +/- 45 g x h(-1) vs. 409 +/- 84
      g x h(-1), respectively). Subjective thermal comfort was not significantly
      different. CONCLUSIONS: TP was more effective than the CV in reducing heat strain
      under the conditions used in the study. Until a significant breakthrough in
      reducing heat strain while wearing NBC clothing in field conditions can be found,
      TP appears to be an effective and recommended cooling method.

PMID- 15152892
TI  - Foot-ground reaction force during resistive exercise in parabolic flight.
AB  - INTRODUCTION: An interim resistance exercise device (iRED) was designed to
      provide resistive exercise as a countermeasure to spaceflight-induced loss of
      muscle strength and endurance as well as decreased bone mineral density. The
      purpose of this project was to compare foot-ground reaction force during iRED
      exercise in normal gravity (1 G) vs. microgravity (0 G) achieved during parabolic
      flight. METHODS: There were four subjects who performed three exercises (squat,
      heel raise, and deadlift) using the iRED during 1 G and 0 G at a moderate
      intensity (60% of maximum strength during deadlift exercise). Foot-ground
      reaction force was measured in the three orthogonal axes (x, y, z) using a force
      plate, and the magnitude of the resultant force vector was calculated (r = square
      root(x2 + y2 + z2)). Linear displacement (LD) was measured using a linear
      transducer. Peak force (Fpeak) and an index of total work (TWi) were calculated
      using a customized computer program. Paired t-tests were used to test if
      significant differences (p < or = 0.05) were observed between 1 G and 0 G
      exercise. RESULTS: Fpeak and TWi measured in the resultant axis were
      significantly less in 0 G for each of the exercises tested. During 0 G, Fpeak was
      42-46% and TWi was 33-37% of that measured during 1 G. LD and average time to
      complete each repetition were not different from 1 G to 0 G. CONCLUSIONS:
      Crewmembers who perform resistive exercises during spaceflight that include the
      movement of a large portion of their body mass will require much greater external
      resistive force during 0 G than 1 G exercise to provide a sufficient stimulus to
      maintain muscle and bone mass.

PMID- 15152893
TI  - Cysteinyl leukotriene blockade does not prevent acute mountain sickness.
AB  - BACKGROUND: Acute Mountain Sickness (AMS) is a multi-system disorder that is
      characterized by headache, anorexia, nausea, vomiting, insomnia, lassitude, and
      malaise. The syndrome is common in unacclimatized low altitude residents who
      rapidly ascend to terrestrial elevations exceeding 2,500 m. AMS may be a
      manifestation of hypoxia-induced cerebral edema resulting, in part, from
      increased capillary permeability. HYPOTHESIS: We hypothesized that cysteinyl
      leukotrienes (CysLTs) may be involved in the pathogenesis of AMS, as these
      compounds are known to increase endothelial permeability. METHODS: To test this
      hypothesis, we orally administered a CysLTs type-1 receptor antagonist
      (montelukast) to 11 subjects prior to and during exposure to high altitude (4,300
      m) in a hypobaric chamber in a randomized, placebo-controlled, crossover design.
      We measured the resulting prevalence and/or severity of AMS, plasma CysLTs levels
      and urinary CysLTE4, and associated physiological responses. RESULTS: At 12 h
      exposure, AMS prevalence and symptom severity was lower (p = 0.002) during
      montelukast administration compared with placebo, but not different at 22 h
      exposure. Plasma CysLTs and urinary LTE4 levels were not significantly elevated
      at 22 h exposure, nor did these CysLTs levels correlate with AMS severity.
      Compared with placebo, montelukast administration was not associated with any
      significant differences in physiologic measures at sea level or high altitude.
      CONCLUSIONS: These results do not support a role for the CysLTs mediating the
      early development of AMS through the CysLT-1 receptor.

PMID- 15152894
TI  - Speed and accuracy of head- and eye-based aiming systems at high vertical
      acceleration.
AB  - BACKGROUND: The benefits of using a head tracker in a fast jet to aim weapons and
      control sensor direction have been amply demonstrated, but head direction is
      difficult to control at high G. An experiment was conducted to assess whether
      aiming using the eye, rather than the head, might be advantageous. METHODS: A
      centrifuge provided sustained accelerations of up to 8 Gz. Participating aircrew
      were asked to point at static targets using head- or eye-aiming, maintain the
      acquisition while the target was lit, and then transfer to the next target as
      quickly as possible. A helmet-mounted scene camera recorded the subject's view of
      the target board. A laser mounted by the scene camera was used for head-aiming
      and to determine head direction. The eye tracker camera and illuminator were also
      helmet-mounted. The eye and scene images were recorded and analyzed off-line.
      RESULTS: Eye-aiming acquisition times and accuracy were affected only slightly by
      Gz; however, both head-aiming speed and accuracy deteriorated as Gz increased.
      Eye-aiming was substantially faster than head-aiming at all Gz levels, but head
      aiming was more accurate under these experimental conditions. Subjective ratings
      supported the objective data. A majority of subjects preferred eye to head as an
      aiming mechanism. CONCLUSIONS: Eye-aiming was faster and easier to use than head
      aiming at all Gz levels, and particularly at high Gz.

PMID- 15152895
TI  - Human factors in maintenance: impact on aircraft mishap frequency and severity.
AB  - INTRODUCTION: Aviation mishaps caused by maintenance factors vary in severity,
      but can cost untold sums in lives and equipment lost. This study proposes to
      demonstrate that certain specific maintenance-related human factors are
      significantly correlated with both mishap frequency and severity. METHODS: Using
      information from the Maintenance Error Information Management System (MEIMS),
      1,016 aircraft mishaps caused by human factors in maintenance were examined.
      These mishaps were previously categorized using the Human Factors Analysis and
      Classification System-Maintenance Extension (HFACS-ME). Frequency analysis was
      used to determine the most common HFACS-ME factors seen in aircraft mishaps.
      Logistic regression techniques were used to describe the relationship between the
      dichotomized outcome of mishap severity and the human factors found in the HFACS
      ME. RESULTS: Inadequate supervision, attention/memory errors, and
      judgment/decision errors were the factors found most often in aircraft mishaps.
      The factors of inadequate design, inadequate adaptability/flexibility, inadequate
      lighting/light, confining workspace, and attention/memory error increased odds of
      being associated with a higher severity mishap. DISCUSSION: Emphasis in training
      and education placed in the first three factors mentioned may reduce overall
      number of mishaps. Concentrating resources on the final five factors may decrease
      the number of severe mishaps.

PMID- 15152896
TI  - Desloratadine shows no effect on performance during 6 h at 8,000 ft simulated
      cabin altitude.
AB  - INTRODUCTION: Sustained vigilance is required by pilots and crew during flight;
      therefore, the use of antihistamines with sedating properties is widely
      prohibited. The purpose of this study was to determine the effects of
      desloratadine, a long-acting, nonsedating antihistamine, on healthy volunteers
      placed under conditions of simulated cabin pressure. METHODS: In a double-blind
      crossover study, 21 subjects randomly received single doses of desloratadine 5
      mg, diphenhydramine 50 mg (active control), and placebo on different days
      separated by washout periods of 7 d. On test days, predose levels of alertness
      and fatigue were determined, as were post-dose levels at 1, 2, 3, 5, and 6 h.
      Measurements included vigilance and tracking, a multi-attribute task battery, the
      Stanford Sleepiness Scale, and pulse oximetry. RESULTS: Desloratadine had no
      detrimental effects on sleepiness or performance of tasks associated with flying
      ability. Conversely, diphenhydramine (active control) caused significantly more
      sleepiness than did the placebo [F (2,40) = 6.52, p < 0.01], as well as impaired
      performance (tracking performance p < 0.05 at 3 h post dose), and an increased
      percentage of omissions (p < 0.05 at 2 h post dose). CONCLUSION: A single dose of
      desloratadine 5 mg did not cause sleepiness and did not impair the performance of
      tasks associated with flying ability.

PMID- 15152897
TI  - Melatonin and zopiclone as facilitators of early circadian sleep in operational
      air transport crews.
AB  - INTRODUCTION: This study was an extension into an operational setting of previous
      laboratory work investigating the use of zopiclone and melatonin to facilitate
      early circadian sleep in transport aircrew. The previous laboratory-based study
      demonstrated that both melatonin and zopiclone were effective in inducing early
      circadian sleep without impacting on psychomotor performance after a 7-h sleep
      period. METHODS: In a repeated measures, placebo-controlled protocol, 30 aircrew
      flew 3 transatlantic missions over which they took each of the 3 medications
      (placebo, sustained-release melatonin 2 mg, or zopiclone 5 mg) at an early body
      clock time (17:00) during their first stopover. They wore wrist actigraphs prior
      to and throughout the missions, took a single dose of their scheduled medication
      immediately prior to their early circadian bedtime, and completed a sleep
      questionnaire on arising from their medicated sleep. RESULTS: The results of the
      actigraphic data show that relative to placebo, aircrew on melatonin and
      zopiclone fell asleep more quickly (melatonin: p < 0.01, zopiclone: p < 0.003),
      slept more (melatonin: p < 0.02, zopiclone: p < 0.005), had fewer awakenings
      after sleep onset (melatonin: p < 0.004, zopiclone: p < 0.01), and spent less
      time awake after sleep onset (melatonin: p < 0.01, zopiclone: p < 0.05). The
      results of the questionnaire data show that relative to placebo, aircrew on
      melatonin and zopiclone experienced less difficulty getting to sleep (melatonin:
      p < 0.0001, zopiclone: p < 0.001), had fewer awakenings (melatonin: p < 0.005,
      zopiclone: p < 0.001), less difficulty returning to sleep after awakening
      (melatonin: p < 0.0001, zopiclone: p < 0.0001), and reported a better sleep
      quality (melatonin: p < 0.0003, zopiclone: p < 0.0004). There were no
      statistically significant differences between melatonin and zopiclone in any of
      the actigraphic or questionnaire sleep parameters. CONCLUSIONS: Melatonin and
      zopiclone, in the dosages we used, are equipotent facilitators of early circadian
      sleep during transmeridian air transport operations.

PMID- 15152899
TI  - Centrifuge braking effects on cardiac arrhythmias occurring at high +Gz
      acceleration.
AB  - Abrupt onset and offset of acceleration induces hemodynamic changes that activate
      a number of reflex cardiovascular responses. At high +Gz on a centrifuge,
      apparently healthy subjects occasionally develop a serious cardiac arrhythmia
      such as supraventricular tachycardia or asystole. We report on four such cases
      and examine the effect of rapid centrifuge braking (1 G x s(-1)) on the
      arrhythmia. It appears that the hemodynamic consequences and reflex responses
      produced by rapid deceleration may have a positive effect on paroxysmal
      supraventricular tachycardia, slowing the heart rate or terminating the
      arrhythmia. On the other hand, deceleration tends to intensify sinus bradycardia.
      If further study confirms these findings, medical monitors and centrifuge
      operators may want to consider using gradual braking in cases of bradycardia.

PMID- 15152898
TI  - Human physiological responses to cold exposure.
AB  - Thermal energy is transferred within and between bodies via several avenues, but
      for most unprotected human cold exposures, particularly during immersion,
      convective heat loss dominates. Lower tissue temperatures stimulate
      thermoreceptors, and the resultant afferent flow elicits autonomic homoeostatic
      responses (thermogenesis and vasoconstriction) that regulate body temperature
      within a narrow range. The most powerful effector responses occur when both
      superficial and deep thermoreceptors are cooled simultaneously, but
      thermoeffector activation can also occur as a result of peripheral cooling alone.
      The responses to cold, and the hazards associated with cold exposure, are
      moderated by factors which influence heat production and heat loss, including the
      severity and duration of cold stimuli, accompanying exercise, the magnitude of
      the metabolic response, and individual characteristics such as body composition,
      age, and gender. Cold stress can quickly overwhelm human thermoregulation with
      consequences ranging from impaired performance to death. This review provides a
      comprehensive overview of the human physiological responses to acute cold
      exposure.

PMID- 15152900
TI  - Aeromedical regulation of aviators using selective serotonin reuptake inhibitors
      for depressive disorders.
AB  - This report, prepared at the request of the Aerospace Medical Association (AsMA),
      reviews the present status of aeromedical regulation of depressive disorders and
      antidepressant medications, emphasizing the role of serotonin specific reuptake
      inhibitors (SSRIs). Aeromedical certifying authorities (CAs) generally prohibit
      pilots from flying with a diagnosed depressive disorder, and also prohibit flying
      while taking antidepressant medications, including SSRIs. Some CAs are
      reassessing these prohibitions, which are based on long aeromedical practices, in
      view of changing medical management of depressive disorders. Many pilots choose
      to fly while depressed, with or without medications, because of the long
      grounding periods mandated by current policies. Some SSRIs have very few
      aeromedically significant side effects. Modern psychiatric practice calls for
      long-term use of medication following clinical recovery from depressive disorders
      in order to prevent recurrent episodes. Given these and other factors, AsMA
      proposes that CAs remove the current absolute prohibitions against pilots flying
      while taking SSRIs, and adopt aeromedical protocols that include carefully
      controlled follow-up and review. AsMA urges all certificatory and regulatory
      authorities to consider immediately instituting a policy of using study groups to
      manage depressed aviators who require SSRI antidepressants. Protocols designed to
      aggressively manage the full spectrum of adverse possibilities related to SSRI
      use may enable the safe use of SSRIs in formerly depressed aviators who suffer no
      aeromedically significant side effects. In these closely managed cases of
      depressive disorders, special issuances or waivers for SSRI use are justified.

PMID- 15152901
TI  - Bioaeronautical lab at CAMI receives ABFT accreditation.

PMID- 15152902
TI  - This month in aerospace medicine history--May 2004.

PMID- 15152903
TI  - Operation solutions in aerospace physiology.

PMID- 15152904
TI  - The health-care budget.

PMID- 15152905
TI  - Organizing your practice for success: vision setting, decision making,
      governance, and communications.
AB  - The ability to make decisions, commit to a plan, and move forward is often the
      Achilles heel of a medical group. With dramatic changes in the health-care
      environment, physicians and medical groups are no longer insulated from external
      forces or the need for good business practices. This article addresses a number
      of steps that medical practices can use to improve their long-term success:
      developing an agreed-upon "vision" for the practice, establishing a sound
      decision-making process, putting into place an effective practice governance
      structure, and taking steps to improve the efficiency and effectiveness of group
      meetings.

PMID- 15152907
TI  - Customer service and the revenue cycle (How do you know you're as good as you
      think you are?).

PMID- 15152906
TI  - Achieving success with billing and collections.
AB  - Practices of all sizes and specialties cite reimbursement management as a
      continuing issue of concern. This article identifies seven categories where
      practices can develop or tighten processes to achieve improved billing and
      collections success. Established and developing practices alike can use these
      categories and components to perform an internal check-up. In addition, this
      approach can act as a prompt for investigating new tools to support internal
      efficiency.

PMID- 15152908
TI  - Physician use of e-mail: the telephone of the 21st century?
AB  - E-mail, as an element of a physician's clinical practice, can provide the means
      to accomplish a variety of tasks more effectively and more efficiently,
      increasing patients' involvement in their care and optimizing face-to-face office
      time. Concerns about billing, improper use, privacy, and confidentiality have
      complicated its introduction and acceptance. This article discusses guidelines
      proposed for clinical use of e-mail and barriers that will need to be overcome to
      move this mode of patient-physician communication into the mainstream.

PMID- 15152909
TI  - Negotiate contracts carefully with part-time doctors.
AB  - Medical practices will increasingly need part-time physicians and indeed are
      becoming aware that many doctors prefer or require only part-time employment.
      This article sketches the emerging demographic patterns fueling this trend and
      discusses some of the contractual details to consider in terms of salary,
      benefits, liability coverage, and noncompete covenants.

PMID- 15152910
TI  - Preventing punitive damages from employment liability claims.
AB  - In general, employers do not have a good grasp of the liability they confront in
      dealing with personnel in terms of hiring, discipline, and firing. Medical
      practices frequently are quite oblivious to the problem. This article discusses
      recent judicial decisions and the ways practices may deal with prevention of
      litigation with special emphasis on management training.

PMID- 15152911
TI  - Coding consultations versus referrals.
AB  - Providers can expedite reimbursement and avoid nomenclature errors by properly
      differentiating between consultations and referrals. Since consultations allow
      higher levels of reimbursement, providers will also avoid possible fraud and
      abuse charges because of such mislabeling.

PMID- 15152912
TI  - Working with your spouse, children, or other close relatives.
AB  - Employing someone you're close to in your medical practice can have many
      advantages. Yet, as many doctors find, employing relatives can also have its
      pitfalls. This article describes the financial benefits of employing a loved one
      in your medical practice. It suggests the specific steps you will need to take to
      legitimize your spouse's, significant other's, or relative's employment. The
      author also explores the personal benefits and drawbacks of employing your spouse
      or significant other. She includes advice from other doctors and spouses who work
      together and establishes 15 ground rules for working with your spouse. Finally,
      the article includes a 10-question self-quiz for you and your spouse or
      significant other to help you decide if working together in your medical practice
      will strengthen or strain your relationship.

PMID- 15152913
TI  - Managing your practice's first impression: the process of front-desk
      reengineering.
AB  - Patients must be regarded as consumers. As such, they are increasingly informed,
      questioning, cost-conscious, technologically savvy, and demanding. Just as health
      plans have developed defined contribution products that offer consumers more
      control over how and where their health-care dollars are spent, practice success
      is linked to reengineering office operations to offer consumers and patients
      greater choice, control, autonomy, and service. Patients and consumers want
      practices that deliver clinical and business services that meet the criteria of
      reliability, effciency, service offerings, patient focus, enthusiasm,
      customization, and trust. Physician practices must also take care to avoid
      destructive and disruptive behaviors and conditions such as noise, interference,
      excessive repetition, long waits, appointment delays, and staff rudeness. A
      successful patient-focused practice emerges when physicians and office staff
      begin to look at the clinical and service experience through the patient's eyes.

PMID- 15152914
TI  - Impact of the Medicare Act on practices.

PMID- 15152915
TI  - The Medicare Act and taxes.

PMID- 15152916
TI  - The physician payment update within the Medicare Act.

PMID- 15152917
TI  - Malpractice litigation reform: empirical approaches to establishing the legal
      standard of care.
AB  - This article proposes that the legal standard of care in malpractice cases should
      be established through empirical methods rather than only with experts'subjective
      opinions. The authors outline and critique two approaches for doing so and
      explain the legal advantages and barriers to implementing these legal reforms.
      Basing the legal standard of care on evidence of actual physician behaviors and
      views would help to improve medical practice by reducing the need to engage in
      defensive medicine and by making it safer to institute quality improvement
      measures.

PMID- 15152918
TI  - In vivo study of human skin using pulsed terahertz radiation.
AB  - Studies in terahertz (THz) imaging have revealed a significant difference between
      skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong
      absorptions at THz frequencies and tumours tend to have different water content
      from normal tissue, a likely contrast mechanism is variation in water content.
      Thus, we have previously devised a finite difference time-domain (FDTD) model
      which is able to closely simulate the interaction of THz radiation with water. In
      this work we investigate the interaction of THz radiation with normal human skin
      on the forearm and palm of the hand in vivo. We conduct the first ever systematic
      in vivo study of the response of THz radiation to normal skin. We take in vivo
      reflection measurements of normal skin on the forearm and palm of the hand of 20
      volunteers. We compare individual examples of THz responses with the mean
      response for the areas of skin under investigation. Using the in vivo data, we
      demonstrate that the FDTD model can be applied to biological tissue. In
      particular, we successfully simulate the interaction of THz radiation with the
      volar forearm. Understanding the interaction of THz radiation with normal skin
      will form a step towards developing improved imaging algorithms for diagnostic
      detection of skin cancer and other tissue disorders using THz radiation.

PMID- 15152919
TI  - Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty
      tissue using exponential functions.
AB  - A therapeutic procedure to treat small, surface breast tumours up to 10 mm in
      radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial
      thermotherapy (LITT) is currently being investigated. The purpose of this study
      is to analyse and model the thermal and coagulative response of ex vivo fibro
      fatty tissue, a model for breast tissue, during experimental laser interstitial
      thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially
      through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to
      produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue
      temperature was measured with thermocouples placed at 15 positions around the
      fibre. The induced coagulation zone was measured on gross anatomical sections.
      Thermal analysis indicates that a finite sum of exponential functions is an
      approximate solution to the heat conduction equation that more accurately
      predicts the time-temperature dependence in tissue prior to carbonization (T <
      100 degrees C) during LITT than the traditional model using a single exponential
      function. Analysis of the ellipsoid coagulation volume induced in tissue
      indicates that the 980 nm wavelength does not penetrate deep enough in fibro
      fatty tissue to produce a desired 30 mm diameter (14.1 x 10(3) mm3) coagulation
      volume without unwanted tissue liquefaction and carbonization.

PMID- 15152920
TI  - The use of gel dosimetry for verification of electron and photon treatment plans
      in carcinoma of the scalp.
AB  - In recent years there has been a large amount of research into the potential use
      of radiation sensitive gels for three-dimensional verification of clinical
      radiotherapy doses. In this paper we report the use of a MAGIC gel dosimeter
      (Fong et al 2001 Phys. Med. Biol. 46 3105) for the verification of a specific
      patient's radiation therapy dose distribution. A 69-year-old male patient
      presented with a squamous cell carcinoma extending approximately 180 degrees
      across the top of the scalp (anterior to posterior) and from just over midline to
      90 degrees left of the skull. The patient's treatment was commenced using two
      electron fields. For gel dosimetry, phantoms were produced in which the outer
      surface spatially corresponded to the outer contours of the patient's anatomy in
      the region of irradiation. The phantoms were treated with either electrons or
      intensity modulated radiation therapy (IMRT) with photons. The results identified
      a hot spot between the matched electron fields and confirmed the more homogeneous
      dose distribution produced by the IMRT planning system. The IMRT plan was then
      clinically implemented. The application of a clinical dose to a phantom shaped to
      a specific patient as well as the ability to select a slice at will during
      phantom imaging means that gel dosimetry can no longer be considered to simply
      have potential alone, but is now in fact a useful dosimetric tool.

PMID- 15152921
TI  - Application of influence diagrams to prostate intensity-modulated radiation
      therapy plan selection.
AB  - The purpose is to incorporate clinically relevant factors such as patient
      specific and dosimetric information as well as data from clinical trials in the
      decision-making process for the selection of prostate intensity-modulated
      radiation therapy (IMRT) plans. The approach is to incorporate the decision
      theoretic concept of an influence diagram into the solution of the multiobjective
      optimization inverse planning problem. A set of candidate IMRT plans was obtained
      by varying the importance factors for the planning target volume (PTV) and the
      organ-at-risk (OAR) in combination with simulated annealing to explore a large
      part of the solution space. The Pareto set for the PTV and OAR was analysed to
      demonstrate how the selection of the weighting factors influenced which part of
      the solution space was explored. An influence diagram based on a Bayesian network
      with 18 nodes was designed to model the decision process for plan selection. The
      model possessed nodes for clinical laboratory results, tumour grading, staging
      information, patient-specific information, dosimetric information, complications
      and survival statistics from clinical studies. A utility node was utilized for
      the decision-making process. The influence diagram successfully ranked the plans
      based on the available information. Sensitivity analyses were used to judge the
      reasonableness of the diagram and the results. In conclusion, influence diagrams
      lend themselves well to modelling the decision processes for IMRT plan selection.
      They provide an excellent means to incorporate the probabilistic nature of data
      and beliefs into one model. They also provide a means for introducing evidence
      based medicine, in the form of results of clinical trials, into the decision
      making process.

PMID- 15152923
TI  - Monitor unit calculation for Monte Carlo treatment planning.
AB  - In this work, we investigate a formalism for monitor unit (MU) calculation in
      Monte Carlo based treatment planning. By relating MU to dose measured under
      reference calibration conditions (central axis, depth of dose maximum in water,
      10 cm x 10 cm field defined at 100 cm source-to-surface distance) our formalism
      determines the MU required for a treatment plan based on the prescription dose
      and Monte Carlo calculated dose distribution. Detailed descriptions and formulae
      are given for various clinical situations including conventional treatments and
      advanced techniques such as intensity-modulated radiotherapy (IMRT) and modulated
      electron radiotherapy (MERT). Analysis is made of the effects of source
      modelling, beam modifier simulation and patient dose calculation accuracy, all of
      which are important factors for absolute dose calculations using Monte Carlo
      simulations. We have tested the formalism through phantom measurements and the
      predicted MU values were consistent with measured values to within 2%. The
      formalism has been used for MU calculation and plan comparison for advanced
      treatment techniques such as MERT, extracranial stereotactic IMRT, MRI-based
      treatment planning and intensity-modulated laser-proton therapy studies. It is
      also used for absolute dose calculations using Monte Carlo simulations for
      treatment verification, which has become part of our comprehensive IMRT quality
      assurance programme.

PMID- 15152922
TI  - Real-time optical-fibre luminescence dosimetry for radiotherapy: physical
      characteristics and applications in photon beams.
AB  - A new optical-fibre radiation dosimeter system, based on radioluminescence and
      optically stimulated luminescence from carbon-doped aluminium oxide, was
      developed and tested in clinical photon beams. This prototype offers several
      features, such as a small detector (1 x 1 x 2 mm3), high sensitivity, real-time
      read-out and the ability to measure both dose rate and absorbed dose. The
      measurements describing reproducibility and output dependence on dose rate, field
      size and energy all had standard deviations smaller than 1%. The signal variation
      with the angle of incidence was smaller than 2% (1 SD). Measurements performed in
      clinical situations suggest the potential of using this real-time system for in
      vivo dosimetry in radiotherapy.

PMID- 15152924
TI  - Modelling 6 MV photon beams of a stereotactic radiosurgery system for Monte Carlo
      treatment planning.
AB  - The goal of this work is to build a multiple source model to represent the 6 MV
      photon beams from a Cyberknife stereotactic radiosurgery system for Monte Carlo
      treatment planning dose calculations. To achieve this goal, the 6 MV photon beams
      have been characterized and modelled using the EGS4/BEAM Monte Carlo system. A
      dual source model has been used to reconstruct the particle phase space at a
      plane immediately above the secondary collimator. The proposed model consists of
      two circular planar sources for the primary photons and the scattered photons,
      respectively. The dose contribution of the contaminant electrons was found to be
      in the order of 10(-3) of the total maximum dose and therefore has been omitted
      in the source model. Various comparisons have been made to verify the dual source
      model against the full phase space simulated using the EGS4/BEAM system. The
      agreement in percent depth dose (PDD) curves and dose profiles between the phase
      space and the source model was generally within 2%/1 mm for various collimators
      (5 to 60 mm in diameter) at 80 to 100 cm source-to-surface distances (SSD).
      Excellent agreement (within 1%/1 mm) was also found between the dose
      distributions in heterogeneous lung and bone geometry calculated using the
      original phase space and those calculated using the source model. These results
      demonstrated the accuracy of the dual source model for Monte Carlo treatment
      planning dose calculations for the Cyberknife system.

PMID- 15152925
TI  - The photon fluence non-uniformity correction for air kerma near Cs-137
      brachytherapy sources.
AB  - The use of brachytherapy sources in radiation oncology requires their proper
      calibration to guarantee the correctness of the dose delivered to the treatment
      volume of a patient. One of the elements to take into account in the dose
      calculation formalism is the non-uniformity of the photon fluence due to the beam
      divergence that causes a steep dose gradient near the source. The correction
      factors for this phenomenon have been usually evaluated by the two theories
      available, both of which were conceived only for point sources. This work
      presents the Monte Carlo assessment of the non-uniformity correction factors for
      a Cs-137 linear source and a Farmer-type ionization chamber. The results have
      clearly demonstrated that for linear sources there are some important differences
      among the values obtained from different calculation models, especially at short
      distances from the source. The use of experimental values for each specific
      source geometry is recommended in order to assess the non-uniformity factors for
      linear sources in clinical situations that require special dose calculations or
      when the correctness of treatment planning software is verified during the
      acceptance tests.

PMID- 15152926
TI  - Incorporation of functional imaging data in the evaluation of dose distributions
      using the generalized concept of equivalent uniform dose.
AB  - Advances in the fields of IMRT and functional imaging have greatly increased the
      prospect of escalating the dose to highly active or hypoxic tumour sub-volumes
      and steering the dose away from highly functional critical structure regions.
      However, current clinical treatment planning and evaluation tools assume
      homogeneous activity/function status in the tumour/critical structures. A method
      was developed to incorporate tumour/critical structure heterogeneous
      functionality in the generalized concept of equivalent uniform dose (EUD). The
      tumour and critical structures functional EUD (FEUD) values were calculated from
      the dose-function histogram (DFH), which relates dose to the fraction of total
      function value at that dose. The DFH incorporates flouro-deoxyglucose positron
      emission tomography (FDG-PET) functional data for tumour, which describes the
      distribution of metabolically active tumour clonogens, and single photon emission
      computed tomography (SPECT) perfusion data for critical structures. To
      demonstrate the utility of the method, the lung dose distributions of two non
      small cell lung cancer patients, who received 3D conformal external beam
      radiotherapy treatment with curative intent, were evaluated. Differences between
      the calculated lungs EUD and FEUD values of up to 50% were observed in the 3D
      conformal plans. In addition, a non-small cell lung cancer patient was inversely
      planned with a target dose prescription of 76 Gy. Two IMRT plans (plan-A and plan
      B) were generated for the patient based on the CT, FDG-PET and SPECT treatment
      planning images using dose-volume objective functions. The IMRT plans were
      generated with the goal of achieving more critical structures sparing in plan-B
      than plan-A. Results show the target volume EUD in plan-B is lower than plan-A by
      5% with a value of 73.31 Gy, and the FEUD in plan-B is lower than plan-A by 2.6%
      with a value of 75.77 Gy. The FEUD plan-B values for heart and lungs were lower
      than plan-A by 22% and 18%, respectively. While EUD values show plan-A is
      marginally better than plan-B in terms of target volumetric coverage, the FEUD
      plan-B values show adequate target function coverage with significant critical
      structure function sparing. In conclusion, incorporating functional data in the
      calculation of EUD is important in evaluating the biological merit of treatment
      plans.

PMID- 15152927
TI  - Investigation of the optimal backscatter for an aSi electronic portal imaging
      device.
AB  - The effects of backscattered radiation on the dosimetric response of the Varian
      aS500 amorphous silicon electronic portal imaging device (EPID) are studied.
      Measurements demonstrate that radiation backscattered from the EPID mechanical
      support structure causes 5% asymmetries in the detected signal. To minimize the
      effect of backscattered radiation from the support structure, this work proposes
      adding material downstream of the EPID phosphor which provides uniform
      backscattering material to the phosphor and attenuates backscatter from the
      support structure before it reaches the phosphor. Two material locations were
      studied: downstream of the existing image cassette and within the cassette,
      immediately downstream of the flat-panel imager glass panel. Monte Carlo
      simulations were used to determine the thicknesses of water, Pb and Cu
      backscattering materials required to saturate the backscattered signal response
      for 6 MV and 18 MV beams for material thicknesses up to 50 mm. Water was unable
      to saturate the backscattered signal for thicknesses up to 50 mm for both
      energies. For Pb, to obtain a signal within 1% of saturation, 3 mm was required
      at 6 MV, and 6.8 mm was required at 18 MV. For Cu, thicknesses of 20.6 mm and
      22.6 mm were required for the 6 MV and 18 MV beams, respectively. For saturation
      thicknesses, at 6 MV, the Cu backscatter enhanced the signal more than for Pb (Cu
      1.25, Pb 1.11), but at 18 MV the reverse was found (Cu 1.19, Pb 1.23). This is
      due to the fact that at 6 MV, the backscattered radiation signal is dominated by
      low-energy scattered photons, which are readily attenuated by the Pb, while at 18
      MV, electron backscatter contributes substantially to the signal. Image blurring
      caused by backscatter spread was less for Pb than Cu. Placing Pb immediately
      downstream of the glass panel further reduced the signal spread and increased the
      backscatter enhancement to 1.20 and 1.39 for the 6 MV and 18 MV beams,
      respectively. Overall, it is determined that adding approximately 5 mm of Pb
      between the detector and the mechanical support structure will substantially
      reduce the nonuniformity in the backscattered signals for 6 MV and 18 MV photon
      beams.

PMID- 15152929
TI  - Functional CT in lung with a conventional scanner: simulations and sampling
      considerations.
AB  - Due to rapid transit times, motion artefacts from breathing and the low signal
      intensity, functional computed tomography (f-CT) studies in lung tissue remain
      challenging with conventional CT scanners. The purpose of this study is to
      examine the accuracy of parameter estimates when performing deconvolution
      analysis with signals from lung tissue. The effects of partial volume averaging
      in lung tissue, differing transit times, variable vascular and capillary
      responses, expected noise levels, differing sampling rate and durations were
      simulated on a computer. Deconvolution using singular-value decomposition (SVD)
      analysis was performed for realistic lung signals using published and measured
      values of the arterial input and noise levels. The accuracy, bias and variance of
      the estimated residue functions and their associated parameter estimates were
      evaluated. We find that f-CT signals may be measured and analysed using SVD and
      other deconvolution approaches. Functional CT signals in the lung may be analysed
      provided that the rise and fall of the tissue and input curves are well sampled
      (regardless of sampling rate) and noise levels in the lung ROI tissue are
      approximately 20 HU or less, even for regions of interest that are mostly
      occupied by air. Estimates of the mean tissue transit time (MTT) are insensitive
      to air volume. Other decovolution methods such as fast Fourier transform methods
      provide more accurate estimates of PBF, whereas SVD approaches provide more
      accurate estimates of pulmonary blood volume and MTT. F-CT of the lung with a
      conventional scanner should be possible, when the extra dose is not a
      consideration.

PMID- 15152928
TI  - Breast tomography with synchrotron radiation: preliminary results.
AB  - A system for in vivo breast imaging with monochromatic x-rays has been designed
      and built at the synchrotron radiation facility Elettra in Trieste (Italy) and
      will be operational in 2004. The system design involves the possibility of
      performing both planar mammography and breast tomography. In the present work,
      the first results obtained with a test set-up for breast tomography are shown and
      discussed. Tomographic images of in vitro breasts were acquired using
      monochromatic x-ray beams in the energy range 20-28 keV and a linear array
      silicon pixel detector. Tomograms were reconstructed using standard filtered
      backprojection algorithms; the effect of different filters was evaluated. The
      attenuation coefficients of fibroglandular and adipose tissue were measured, and
      a quantitative comparison of images acquired at different energies was performed
      by calculating the differential signal-to-noise ratio of fibroglandular details
      in adipose tissue. All images required a dose comparable to the dose delivered in
      clinical, conventional mammography and showed a high resolution of the breast
      structures without the overlapping effects that limit the visibility of the
      structures in 2D mammography. A quantitative evaluation of the images proves that
      the image quality at a given dose increases in the considered energy range and
      for the considered breast sizes.

PMID- 15152930
TI  - Total body water measurements using resonant cavity perturbation techniques.
AB  - A recent paper proposed a novel technique for determining the total body water
      (TBW) of patients suffering with abnormal hydration levels, using a resonant
      cavity perturbation method. Current techniques to measure TBW are limited by
      resolution and technical constraints. However, this new method involves measuring
      the dielectric properties of the body, by placing a subject in a large cavity
      resonator and measuring the subsequent change in its resonant frequency, fres and
      its Q-factor. Utilizing the relationship that water content correlates to these
      dielectric properties, it has been shown that the measured response of these
      parameters enables determination of TBW. Results are presented for a preliminary
      study using data estimated from anthropometric measurements, where volunteers
      were asked to lie and stand in an electromagnetic screened room, before and after
      drinking between 1 and 2 l of water, and in some cases, after voiding the
      bladder. Notable changes in the parameters were observed; fres showed a negative
      shift and Q was reduced. Preliminary calibration curves using estimated values of
      water content have been developed from these results, showing that for each
      subject the measured resonant frequency is a linear function of TBW. Because the
      gradients of these calibration curves correlate to the mass-to-height-ratio of
      the volunteers, it has proved that a system in which TBW can be unequivocally
      obtained is possible. Measured values of TBW have been determined using this new
      pilot-technique, and the values obtained correlate well with theoretical values
      of body water (r = 0.87) and resolution is very good (750 ml). The results
      obtained are measurable, repeatable and statistically significant. This leads to
      confidence in the integrity of the proposed technique.

PMID- 15152931
TI  - Deterministic nonlinear characteristics of in vivo blood flow velocity and
      arteriolar diameter fluctuations.
AB  - We have performed a nonlinear analysis of fluctuations in red cell velocity and
      arteriolar calibre in the mesenteric bed of the anaesthetized rat. Measurements
      were obtained under control conditions and during local superfusion with NG-nitro
      L-arginine (L-NNA, 30 microM) and tetrabutylammonium (TBA, 0.1 mM), which
      suppress NO synthesis and block Ca2+ activated K+ channels (KCa), respectively.
      Time series were analysed by calculating correlation dimensions and largest
      Lyapunov exponents. Both statistics were higher for red cell velocity than
      diameter fluctuations, thereby potentially differentiating between global and
      local mechanisms that regulate microvascular flow. Evidence for underlying
      nonlinear structure was provided by analysis of surrogate time series generated
      from the experimental data following randomization of Fourier phase. Complexity
      indices characterizing time series under control conditions were in general
      higher than those derived from data obtained during superfusion with L-NNA and
      TBA.

PMID- 15152932
TI  - New thermoluminescent dosimeters (TLD): optimization and characterization of TLD
      threads sterilizable by autoclave.
AB  - To improve the performance of mono-extruded TLD threads as a dosimetric
      thermoluminescent tool (French Patent 9903729), a new process was developed by co
      extrusion methodology leading to threads of 600 microm diameter with a 50 microm
      homogeneous polypropylene sheath. In this optimization work, study of parameters
      such as LiF:Mg,Cu,P powder granulometry, load rate and proportion of components
      led to an increased sensitivity of around 40%. Moreover, the co-extrusion
      technique allowed the threads to be sterilized by humid steam (134 degrees C/18
      min) without significant variation of the linearity response between 0 and 30 Gy
      after gamma irradiation (60Co).

PMID- 15152933
TI  - The potential application of beta-delayed particle decay beam 9C in cancer
      therapy.
AB  - A radioactive ion beam like 9C serves as a double radiation source and may be
      useful in cancer treatment, where the essential irradiation comes from the
      external beam itself and the extra one is due to the low-energy particles emitted
      internally during the decay of 9C. Based on the microdosimetric specific energy
      spectrum in cell nuclei, a model to evaluate the biological effect induced by the
      internally emitted particles from a beta-delayed particle decay beam has been
      developed. In this paper, using this model the additional contributions to the
      cell-killing effect due to the emitted particles from stopping 9C ions were
      incorporated in the design of spread-out Bragg peaks (SOBP) for radioactive 9C
      beams. For this purpose, a simulated annealing algorithm was employed to optimize
      the superposing weighting fractions of all monoenergetic beams so that a uniform
      cell survival level could be realized across the SOBP within an acceptable
      deviation of 5%. SOBPs with different widths and at different cell survival
      levels were designed for both therapeutic 9C and 12C beams for comparison. The
      potential use of the 9C beam in radiotherapy compared to the 12C beam, which is
      commonly adopted in the practices of current heavy-ion therapy, is shown
      systematically in terms of the distributions of biological effective dose and
      cell survival along the beam penetration.

PMID- 15152934
TI  - Neutron dose from prostheses material during radiotherapy with protons and
      photons.
AB  - The purpose of this investigation is to measure the impact of Ti-alloy-prostheses
      on the neutron dose during proton and photon radiotherapy. Such unwanted neutron
      dose to the patient should be kept as low as possible (ALARA principle), as such
      additional dose can create secondary malignancies. For this purpose we performed
      neutron dose measurements using etch track detectors under the same conditions on
      a proton and a photon beam line used for radiotherapy. We found no influence of
      the prostheses material on the neutron dose both for proton and photon treatment.

PMID- 15152935
TI  - Radiation phantom with humanoid shape and adjustable thickness (RPHAT).
AB  - A new radiation phantom with humanoid shape and adjustable thickness (RPHAT) has
      been developed. Unlike the RANDO phantom which is a fixed thickness, this newly
      designed phantom has adjustable thickness to address the range of thicknesses of
      real-world patients. RPHAT allows adjustment of the body thickness by being
      sliced in the coronal (instead of axial) direction. Centre slices are designed so
      that more sections can be added or removed while maintaining the anthropomorphic
      shape. A prototype of the new phantom has been successfully used in a study
      investigating peripheral dose delivery, where the amount of scatter within the
      patient, and therefore the patient thickness, plays a critical role in dose
      deposition. This newly designed phantom is an important tool to improve the
      quality of radiation therapy.

PMID- 15152936
TI  - Antivascular and antitumor activities of liposome-associated drugs.
AB  - Particulate drug carriers offer unique opportunities to improve tumor therapy
      through several different mechanisms. Liposomes may (1) assist in formulation of
      poorly-soluble therapeutic agents, (2) provide a slow-release vehicle to achieve
      pharmacokinetic profiles that maximize the therapeutic index, or (3) behave as
      long-circulating nano-particulates that can extravasate in the hyperpermeable
      regions of tumor vasculature. For paclitaxel, liposomes provide an aid to
      formulation. In the intracranial rat 9L brain tumor model, paclitaxel liposomes
      reduced dose-limiting toxicity and mediated a 40% increase in median survival.
      Free drug did not extend survival. Doxorubicin entrapped within sterically
      stabilized liposomes (SSL-DXR) represents a long-circulating formulation that can
      extravasate within tumors and enhance drug deposition. Repetitive dosing with SSL
      DXR mediated a 30% extension in median lifespan of animals bearing advanced 9L
      tumors. Fluorescence microscopic imaging revealed non-uniform, sporadic
      deposition of liposomes within the tumor. Magnetic resonance imaging showed that
      repetitive dosing with SSL-DXR, but not free drug, resulted in vascular collapse
      and microhemorrhage within tumors. Exploiting this antivascular effect may
      provide a new means to enhance tumor therapy, and suggests the utility of
      combination therapy with agents such as paclitaxel that have antiangiogenic
      effects on tumors.

PMID- 15152937
TI  - Adriamycin alters the expression of drug efflux pumps and confers amphotericin B
      tolerance in Candida albicans.
AB  - The aim of the work presented here was to establish whether exposure of the yeast
      C. albicans to adriamycin altered the expression of the CDR1 drug efflux pump and
      consequently altered the susceptibility of the yeast to amphotericin B. Using a
      monoclonal antibody directed against human MDR1 and polyclonal antibodies against
      CDR1 (Candida drug resistance), we demonstrated that adriamycin induces an
      elevation in the expression of the CDR1 efflux pump which, together with
      previously recorded alterations in the composition of the fungal cell membrane,
      may confer tolerance to amphotericin B. This work highlights the fact that
      adriamycin therapy may inadvertently alter the susceptibility of C. albicans to
      amphotericin B, which may have deleterious consequences for anti-cancer
      chemotherapy regimes incorporating this anti-neoplastic agent.

PMID- 15152938
TI  - Structure-activity analysis of taxane-based broad-spectrum multidrug resistance
      modulators.
AB  - BACKGROUND: Clinical drug resistance is frequently associated with overexpression
      of the multidrug resistance (MDR) proteins P-glycoprotein (Pgp), multidrug
      resistance protein (MRP-1) and breast cancer resistance protein (BCRP). Taxanes
      are substrates for Pgp and MRP-1, but not BCRP. Taxane-based reversal agents
      (tRAs) are non-cytotoxic MDR modulators previously examined for broad-spectrum
      modulation of Pgp, MRP-1 and BCRP. MATERIALS AND METHODS: Modulation by tRAs was
      studied by flow cytometry and resistance to taxanes was studied in cytotoxicity
      assays in the parental HL60/wt, 8226/wt and MCF7/S, and the resistant HL60/ADR,
      8226/Dox6, 8226/MR20 and MCF7 AdVp3000 cell lines. Amino acid sequence (BLAST)
      alignments were performed using ClustalW. RESULTS: Structure-activity analysis
      demonstrated greatest alignment of BCRP with the transmembrane 7-12 region of Pgp
      and identified tRA side groups that contributed or were detrimental to
      modulation. CONCLUSION: Identification of tRA side groups contributing to
      modulation of Pgp, MRP-1 and BCRP will allow the design of a next generation of
      tRAs and will optimize their potential clinical applicability.

PMID- 15152939
TI  - 5-Fluorouracil: identification of novel downstream mediators of tumour response.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is routinely used in the treatment of
      gastrointestinal, breast and head and neck cancers. A major limitation to the use
      of this drug is acquired or inherent resistance. MATERIALS AND METHODS: To
      examine the downstream molecular signals activated in response to 5-FU, we used
      DNA microarray technology to examine global transcriptional changes in 5-FU
      treated MCF-7 breast cancer cells. RESULTS: We identified several novel 5-FU
      inducible target genes that have not previously been linked to 5-FU response,
      including spermine/spermidine acetyl transferase (SSAT) and annexin II. Treatment
      of MCF-7 cells with the antifolate tomudex (TDX) and the DNA damaging agent
      oxaliplatin also caused up-regulation of each target gene. Inactivation of wild
      type p53 abrogated the 5-FU-mediated induction of SSAT and annexin II. Inducible
      expression of thymidylate synthase completely abrogated TDX-, but not 5-FU
      mediated induction of each gene. Furthermore, basal expression of SSAT and
      annexin II was elevated in cells resistant to 5-FU. CONCLUSION: These data
      demonstrate the potential of microarray analysis to identify novel genes
      associated with response or resistance to chemotherapeutic agents.

PMID- 15152940
TI  - Construction and transfection of a ribozyme targeting human caspase-3.
AB  - Caspase-3 is a key executioner cysteine protease involved in programmed cell
      death or apoptosis. A ribozyme to human caspase-3 was designed, tested by in
      vitro cleavage, and transfected into a drug-resistant variant (DLKP-A5F) of a
      human lung carcinoma cell line (DLKP). By both stable and transient transfection,
      this ribozyme was shown to be effective at down-regulating human caspase-3 mRNA
      and protein levels.

PMID- 15152941
TI  - Two-deoxyglucose as an anti-metabolite in human carcinoma cell line RPMI-2650 and
      drug-resistant variants.
AB  - The accumulation of 2-deoxyglucose (2-DG), a glycolytic inhibitor, was
      investigated in a human nasal carcinoma cell line, RPMI-2650 and two of its drug
      resistant variants (selected with taxol and melphalan) to assess manipulation of
      glycolytic potential as a selective means of reducing resistance. 2-DG uptake was
      increased 3-fold and 9.9-fold in taxol- and melphalan-resistant variants of RPMI
      2650, respectively. Two of the principal factors associated with increased 2-DG
      uptake, namely glucose transporters and hexokinase activity, were increased in
      the resistant variants. Other changes in glucose metabolism that may affect 2-DG
      as an antimetabolite were observed, including increases in glucose-6-phosphate
      dehydrogenase of 10-fold and 100-fold for taxol- and melphalan-resistant
      variants, respectively, suggesting higher pentose phosphate activity; increased
      glutamine utilisation and greater sensitivity to iodoacetic acid-induced
      depletion of ATP levels in the parent relative to the resistant variants.

PMID- 15152942
TI  - Microarrays in cancer research.
AB  - Microarray technology has presented the scientific community with a compelling
      approach that allows for simultaneous evaluation of all cellular processes at
      once. Cancer, being one of the most challenging diseases due to its polygenic
      nature, presents itself as a perfect candidate for evaluation by this approach.
      Several recent articles have provided significant insight into the strengths and
      limitations of microarrays. Nevertheless, there are strong indications that this
      approach will provide new molecular markers that could be used in diagnosis and
      prognosis of cancers. To achieve these goals it is essential that there is a
      seamless integration of clinical and molecular biological data that allows us to
      elucidate genes and pathways involved in various cancers. To this effect we are
      currently evaluating gene expression profiles in human brain, ovarian, breast and
      hematopoetic, lung, colorectal, head and neck and biliary tract cancers. To
      address the issues we have a joint team of scientists, doctors and computer
      scientists from two Virginia Universities and a major healthcare provider. The
      study has been divided into several focus groups that include; Tissue Bank
      Clinical & Pathology Laboratory Data, Chip Fabrication, QA/QC, Tissue
      Devitalization, Database Design and Data Analysis, using multiple microarray
      platforms. Currently over 300 consenting patients have been enrolled in the study
      with the largest number being that of breast cancer patients. Clinical data on
      each patient is being compiled into a secure and interactive relational database
      and integration of these data elements will be accomplished by a common
      programming interface. This clinical database contains several key parameters on
      each patient including demographic (risk factors, nutrition, co-morbidity,
      familial history), histopathology (non genetic predictors), tumor, treatment and
      follow-up information. Gene expression data derived from the tissue samples will
      be linked to this database, which allows us to query the data at multiple levels.
      The challenge of tissue acquisition and processing is of paramount importance to
      the success of this venture. A tissue devitalization timeline protocol was
      devised to ensure sample and RNA integrity. Stringent protocols are being
      employed to ascertain accurate tumor homogeneity, by serial dissection of each
      tumor sample at 10 microM frozen sections followed by histopathological
      evaluation. The multiple platforms being utilized in this study include
      Affimetrix, Oligo-Chips and custom-designed cDNA arrays. Selected RNA samples
      will be evaluated on each platform between the groups. Analysis steps will
      involve normalization and standardization of gene expression data followed by
      hierarchical clustering to determine co-regulation profiles. The aim of this
      conjoint effort is to elucidate pathways and genes involved in various cancers,
      resistance mechanisms, molecular markers for diagnosis and prognosis.

PMID- 15152943
TI  - Functional studies on the MRP1 multidrug transporter: characterization of ABC
      signature mutant variants.
AB  - BACKGROUND: MRP1 is a key multidrug resistance ATP-binding Cassette (ABC)
      transporter in tumor cells. A functionally important signature motif is conserved
      within all ABC domains. Our current studies aimed to elucidate the role of these
      motifs in the cooperation of MRP1 ABC domains. MATERIALS AND METHODS: We designed
      human MRP1 mutants based on a bacterial ABC structure. Conserved leucines (Leu)
      were replaced by arginines (Arg), while glycines (Gly) were substituted for
      aspartic acids (Asp). The activity of these mutants was assayed by measuring
      ATPase activity and vesicular transport. ATP-binding and transition-state
      formation were studied by a photoreactive ATP analog. RESULTS: The Leu to Arg
      mutants retained both ATPase and transport activity, while the Gly to Asp mutants
      were inactive in all functional assays, while showing normal ATP-binding.
      CONCLUSION: Our results reinforce the notion that a single mutation in one of the
      ABC-signature regions affects the function of the whole protein. The relative
      role of the conservative leucines and glycines in MRP1 indicates a similar three
      dimensional structure within the catalytic center of various ABC proteins.

PMID- 15152944
TI  - Increased anti-tumour efficacy of doxorubicin when combined with sulindac in a
      xenograft model of an MRP-1-positive human lung cancer.
AB  - BACKGROUND: A number of cellular proteins, including P-glycoprotein (P-gp) and
      Multiple drug Resistance Protein (MRP-1), act as drug efflux pumps and are
      important in the resistance of many cancers to chemotherapy. We previously
      reported that a small number of NSAIDs could inhibit the activity of MRP-1.
      MATERIALS AND METHODS: We chose sulindac as a candidate agent for further
      investigation as it has the most favourable efficacy and toxicity profile of the
      agents available for a potential specific MRP-1 inhibitor. NCI H460 cells
      expressed MRP-1 protein (by Western blot) and also the toxicity of doxorubicin (a
      substrate of MRP-1) could be potentiated in this line using non-toxic
      concentrations of the MRP-1 substrate/inhibitor sulindac. These cells were
      implanted in nude mice and the animals divided into various groups which were
      administered doxorubicin and/or sulindac. RESULTS: Sulindac was shown to
      significantly potentiate the tumour growth inhibitor activity of doxorubicin in
      this MRP-1-overexpressing human tumour xenograft model. CONCLUSION: Sulindac may
      be clinically useful as an inhibitor of the MRP-1 cancer resistance mechanism.

PMID- 15152945
TI  - Cellular models of drug- and radiation-resistant small cell lung cancer.
AB  - BACKGROUND: The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the
      classic small cell lung cancer (SCLC) line have proven useful in studies of
      resistance and its circumvention with paclitaxel. MATERIALS AND METHODS: The
      suppressor/oncogene profile of these sublines determined by Western and Northern
      blot was compared to the variant H82 SCLC cell profile. Two-dimensional
      electrophoresis/mass spectrometry was used to determine the effect of paclitaxel
      on protein expression. RESULTS: The H69-EPR and H69-CP resistant sublines were
      similar to the variant H82 cells for bcl-2, p21waf1, p53, N-myc and c-myc
      expression while the H69-VP subline retained the classic H69 pattern. A 1-h
      treatment with 10 ng/ml paclitaxel substantially reversed the resistance except
      for the H69/R38 subline and tended to reverse the resistance-associated changes
      in protein expression in the H69-EPR subline. CONCLUSION: Although some resistant
      sublines express a variant pattern of suppressor/oncogenes with low bcl-2,
      resistance is substantially reversed by paclitaxel treatment.

PMID- 15152946
TI  - Expression and prognostic relevance of Mcl-1 in breast cancer.
AB  - BACKGROUND: Bcl-2, an anti-apoptotic protein, is frequently associated with
      favourable prognosis in breast cancer. The potential role of mcl-1, another bcl-2
      family member, in breast cancer has not yet been defined. PATIENTS AND METHODS:
      This study examined the expression of mcl-1 and bcl-2 in 170 cases of invasive
      primary breast carcinoma, using reverse-transcriptase polymerase chain reaction
      and immunohistochemical analyses. RESULTS: Expression of bcl-2 mRNA and protein
      were found to be favourably associated with outcome for patients, supporting a
      prognostic role for bcl-2 in breast cancer, whereas mcl-1 expression, at the mRNA
      or protein level, did not correlate with tumour size, grade, lymph node or ER
      status, age of patient at diagnosis, or disease outcome. CONCLUSION: As these
      analyses of mcl-1 expression may have co-detected mcl-1(S/deltaTM) (a more
      recently identified, shorter variant, that may be pro-apoptotic) with the anti
      apoptotic wild-type of mcl-1, it is possible that future studies may indicate
      some significant clinical correlations if the isoforms can be independently
      investigated.

PMID- 15152947
TI  - A novel gene delivery system for mammalian cells.
AB  - Although gene therapy holds great promise for the treatment of both acquired and
      genetic diseases, its development has been limited by practical considerations.
      Non-viral efficacy of delivery remains quite poor. We are investigating the
      feasibility of a novel lipid-based delivery system, cochleates, to deliver
      transgenes to mammalian cells. Rhodamine-labelled empty cochleates were incubated
      with two cell-lines (4T1 adenocarcinoma and H36.12 macrophage hybridoma) and
      primary macrophages in vitro and in vivo. Cochleates containing green fluorescent
      protein (GFP) expression plasmid were incubated with 4T1 adenocarcinoma cells.
      Cellular uptake of labelled cochleates or transgene GFP expression were
      visualised with fluorescence microscopy. 4T1 and H36.12 lines showed 39% and
      23.1% uptake of rhodamine-cochleates, respectively. Human monocyte-derived
      macrophages and mouse peritoneal macrophages had 48+/-5.38% and 51.46+/-15.6%
      uptake of rhodamine-cochleates in vitro. In vivo 25.69+/-0.127% of peritoneal
      macrophages were rhodamine-positive after intra-peritoneal injection of rhodamine
      cochleates. 19.49+/-10.12% of 4T1 cells expressed GFP. Cochleates may therefore
      be an effective, non-toxic and non-immunogenic method to introduce transgenes in
      vitro and in vivo.

PMID- 15152948
TI  - Increased invasion and expression of MMP-9 in human colorectal cell lines by a
      CD44-dependent mechanism.
AB  - BACKGROUND: In order to investigate the interactions between MMPs and CD44 we
      stably transfected a non-invasive colon cell line, SW480 with the cDNA for MMP-9
      and investigated the effect on CD44 expression and in vitro invasion and
      migration. MATERIALS AND METHODS: In vitro invasion and migration assays were
      carried out using Biocoat matrigel invasion chambers. MMP and CD44 expression was
      determined using zymography, Western blot analysis and RT-PCR. RESULTS:
      Transfection of the parental SW480 cells with the cDNA for MMP-9 (SW480M9) caused
      increased invasion and migration. MMP-9 expression increased when the SW480M9
      cells were grown on HA and collagen and cultured in the presence of a CD44
      activating antibody. Treatment of the cells with HA and a CD44-activating
      antibody also resulted in increased invasion, migration and attachment.
      CONCLUSION: These results demonstrated that CD44 and MMP interactions are
      important in controlling tumour cell invasion and migration.

PMID- 15152949
TI  - Activity of novel plant extracts against medullary thyroid carcinoma cells.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing
      tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be
      relatively insensitive to conventional chemotherapy. MATERIALS AND METHODS: Eight
      cell lines were established from MTCs; each showed an up-regulation of Bcl-2. We
      investigated ten agents from plants of the genera Stemona (Stemonaceae), Aglaia
      (Meliaceae) and Artemisia (Asteraceae) for their effects on proliferation and
      apoptotic rates. Extracts have been used in traditional Chinese medicine;
      however, no experience on their effects on medullary thyroid carcinomas has been
      reported so far. Growth kinetics and viability were examined using the Casy-1
      Cell Counter & Analyzer and the WST-1-based cytotoxicity assay. Apoptosis was
      studied by DAPI staining, by measurement of caspase-3 activity and Bcl-2
      expression. RESULTS: A strong antiproliferative effect was recognized in each
      Aglaia species and with Artesunate, whereas an enhancement of apoptosis was
      provoked particularly by Stemona tuberosa Lour. CONCLUSION: The activity of the
      novel plant extracts possiby offers a new approach towards successful
      chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.

PMID- 15152950
TI  - Cancer gene therapy: challenges and opportunities.
AB  - Understanding the molecular basis of human disease has been the corner-stone of
      rationally designed molecular therapies. Medicine has a long history of treating
      patients with cell therapies (i.e., blood transfusions) and protein therapies
      (i.e., growth factors and cytokines). Gene therapies are the newest therapeutic
      strategy for treating human diseases. Where will gene therapy be in five years
      after the euphoria and frustrations of the last 14 years? This is a complex
      question, but the primary challenge for gene therapy will be to successfully
      deliver an efficacious dose of a therapeutic gene to the defective tissue. Will
      the delivery systems return to the early clinical trials of ex vivo gene therapy
      or will there still be a high demand for systemic therapy? Will systemic therapy
      continue to depend on viral vectors, or will non-viral and nano-particles become
      the new mode for gene delivery? The future success of gene therapy will be built
      on achievements in other fields, such as medical devices, cell therapy, protein
      therapy and nano-particle technology. This review describes the advances being
      made in the gene therapy field, as well as addressing the challenges of the near
      future for cancer gene therapy.

PMID- 15152951
TI  - Endoscopy for Barrett's esophagus and esophageal adenocarcinoma.

PMID- 15152952
TI  - Screening for Barrett's esophagus.

PMID- 15152953
TI  - The use of emergent lateral canthotomy to restore vision.

PMID- 15152954
TI  - Psychotherapy and medication options for depression.

PMID- 15152955
TI  - Functional health literacy: improving health outcomes.

PMID- 15152956
TI  - Vaginal estrogen preparations for relief of atrophic vaginitis.

PMID- 15152957
TI  - Barrett's esophagus.
AB  - Gastroesophageal reflux disease (GERD) is a condition commonly managed in the
      primary care setting. Patients with GERD may develop reflux esophagitis as the
      esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated
      reflux esophagitis may lead to chronic complications such as esophageal stricture
      or the development of Barrett's esophagus. Barrett's esophagus is a premalignant
      metaplastic process that typically involves the distal esophagus. Its presence is
      suspected by endoscopic evaluation of the esophagus, but the diagnosis is
      confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors
      for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing
      age, smoking, and obesity. Although Barrett's esophagus rarely progresses to
      adenocarcinoma, optimal management is a matter of debate. Current treatment
      guidelines include relieving GERD symptoms with medical or surgical measures
      (similar to the treatment of GERD that is not associated with Barrett's
      esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have
      been published; however, no studies have verified that any specific treatment or
      management strategy has decreased the rate of mortality from adenocarcinoma.

PMID- 15152958
TI  - Information from your family doctor. Barrett's esophagus--what should I know
      about it?

PMID- 15152959
TI  - Diagnosis and treatment of acne.
AB  - Acne can cause significant embarrassment and anxiety in affected patients. It is
      important for family physicians to educate patients about available treatment
      options and their expected outcomes. Topical retinoids, benzoyl peroxide,
      sulfacetamide, and azelaic acid are effective in patients with mild or moderate
      comedones. Topical erythromycin or clindamycin can be added in patients with mild
      to moderate inflammatory acne or mixed acne. A six-month course of oral
      erythromycin, doxycycline, tetracycline, or minocycline can be used in patients
      with moderate to severe inflammatory acne. A low-androgen oral contraceptive pill
      is effective in women with moderate to severe acne. Isotretinoin is reserved for
      use in the treatment of the most severe or refractory cases of inflammatory acne.
      Because of its poor side effect profile and teratogenicity, isotretinoin
      (Accutane) must by prescribed by a physician who is a registered member of the
      manufacturer's System to Manage Accutane-Related Teratogenicity program.

PMID- 15152960
TI  - Information from your family doctor. Acne.

PMID- 15152962
TI  - Information from your family doctor. Polycythemia vera.

PMID- 15152961
TI  - Polycythemia vera.
AB  - Polycythemia vera is a chronic myeloproliferative disorder characterized by
      increased red blood cell mass. The resultant hyperviscosity of the blood
      predisposes such patients to thrombosis. Polycythemia vera should be suspected in
      patients with elevated hemoglobin or hematocrit levels, splenomegaly, or portal
      venous thrombosis. Secondary causes of increased red blood cell mass (e.g., heavy
      smoking, chronic pulmonary disease, renal disease) are more common than
      polycythemia vera and must be excluded. Diagnosis is made using criteria
      developed by the Polycythemia Vera Study Group; major criteria include elevated
      red blood cell mass, normal oxygen saturation, and palpable splenomegaly.
      Untreated patients may survive for six to 18 months, whereas adequate treatment
      may extend life expectancy to more than 10 years. Treatment includes phlebotomy
      with the possible addition of myelosuppressive agents based on a risk-stratified
      approach. Agents under investigation include interferon alfa-2b, anagrelide, and
      aspirin. Consultation with a hematologist is recommended.

PMID- 15152963
TI  - Health care screening for men who have sex with men.
AB  - Men who have sex with men often do not reveal their sexual practices or sexual
      orientation to their physician. Lack of disclosure from the patient, discomfort
      or inadequate training of the physician, perceived or real hostility from medical
      staff, and insufficient screening guidelines limit preventive care. Because of
      greater societal stresses, lack of emotional support, and practice of unsafe sex,
      men who have sex with men are at increased risk for sexually transmitted diseases
      (including human immunodeficiency virus infection), anal cancer, psychologic and
      behavioral disorders, drug abuse, and eating disorders. Recent trends indicate an
      increasing rate of sexual risk-taking among these men, particularly if they are
      young. Periodic screening should include a yearly health risk and physical
      assessment as well as a thorough sexual and psychologic history. The physician
      should ask questions about sexual orientation in a nonjudgmental manner;
      furthermore, confidentiality should be addressed and maintained. Office practices
      and staff should be similarly nonjudgmental, with confidentiality maintained.
      Targeted screening for sexually transmitted diseases, depression, substance
      abuse, and other disorders should be performed routinely. Screening guidelines,
      while inconsistent and subject to change, offer some useful suggestions for the
      care of men who have sex with men.

PMID- 15152964
TI  - Evaluation of the patient with chronic cough.
AB  - Patients with chronic cough should avoid exposure to irritants that can trigger
      cough, and those who smoke should stop smoking. Patients who develop chronic
      cough in association with angiotensin-converting enzyme inhibitor therapy should
      be switched to an agent from another drug class. If cough persists, a chest
      radiograph should be ordered to rule out malignancy and other serious conditions.
      Postnasal drip syndrome, asthma, and gastroesophageal reflux disease are the most
      likely causes of chronic cough in adults. If postnasal drip syndrome is
      suspected, a trial of a decongestant and a first-generation antihistamine is
      warranted. Pulmonary function testing with a methacholine challenge is the
      preferred test for confirming the diagnosis of asthma. Gastroesophageal reflux
      disease usually is diagnosed based on the symptoms and after a trial of therapy.
      If the cause of chronic cough remains unclear, high-resolution computed
      tomographic scanning of the chest, bronchoscopy, and referral to a pulmonary
      specialist may be indicated. The approach to diagnosing chronic cough in
      immunocompromised patients and children is similar to the approach in
      immunocompetent adults. However, a CD4+ cell count can help determine the
      potential for opportunistic infections in immunocompromised patients. Respiratory
      tract infections, asthma, and gastroesophageal reflux disease are the most common
      causes of chronic cough in children. Foreign body aspiration should be considered
      in young children. Congenital conditions, cystic fibrosis, and immune disorders
      are possible diagnoses in children with chronic cough and recurrent infection.

PMID- 15152965
TI  - Information from your family doctor. Chronic cough.

PMID- 15152967
TI  - Information from your family doctor. Vaginal yeast infections.

PMID- 15152966
TI  - Skin mass on neck.

PMID- 15152968
TI  - Information from your family doctor. Vaginal discharge.

PMID- 15152969
TI  - Information from your family doctor. Bacterial vaginosis.

PMID- 15152970
TI  - Sinus and Allergy Health Partnership releases report on adult chronic
      rhinosinusitis.
AB  - The report states that chronic rhinosinusitis is an evolving area of study and
      new information is being assessed on an ongoing basis. Debate continues about
      potential etiologies and associated conditions, pathophysiology, common
      inflammatory mediators, and whether or not most cases of chronic rhinosinusitis
      are associated with infection. Evidence in the most recent literature supports
      the significant role that microbes (i.e., bacteria, fungi) play in the
      inflammatory process. The report discusses classification schemes, the role of
      potential bacterial, allergic, and fungal etiologies, and the controversies about
      these areas of study.

PMID- 15152971
TI  - The right to know--but at what cost?

PMID- 15152972
TI  - The decomposition of cost efficiency: an empirical application of the shadow cost
      function model to Dutch general hospitals.
AB  - This paper investigates the performance of the Dutch general hospital industry by
      a parametric method. In general, the parametric approaches find more difficulties
      in distinguishing between technical and allocative efficiencies than DEA. Only
      recently a class of models is developed based on shadow prices which have
      possibilities to distinguish between technical and allocative efficiency.
      However, these models cause some serious computational problems. This paper
      recommends an approach to overcome these problems by using an iterative two-stage
      estimation procedure. The estimation is conducted on a panel data set of Dutch
      general hospitals. Estimation shows that this method is effective. The parameter
      estimates are plausible, reliable and satisfy all theoretical requirements. In
      particular we find some reliable estimates for the individual hospitals' shadow
      prices. According to these shadow prices hospitals should reallocate their
      resources in favor of material supplies at the cost of other personnel and
      nursing personnel. The mean technical efficiency is about 86%, whereas the
      allocative efficiency is about 92%. The outcomes also show that technical
      progress is very small. Economies of scale are present only for small hospitals.

PMID- 15152973
TI  - Analysis of the expenses linked to hospital stays: how to detect outliers.
AB  - When hospital financing depends on a budget which in turn depends on the
      pathologies being treated, it is necessary to detect hospital stays which show
      discrepancies between the resources they consume and the medical characteristics
      they present. Deterministic nonparametric frontier models are used to rank
      hospital stays according to their expenses taking into account the severity of
      the patients' conditions. As these models are very sensitive to the extreme
      stays, a robust frontier model, the order-m frontier is used. The too-efficient
      stays are highlighted and described. The mean expenses are estimated after
      excluding too-efficient and inefficient stays. This mean is higher than the mean
      estimated by using classical trimming rules.

PMID- 15152974
TI  - Estimating procedure times for surgeries by determining location parameters for
      the lognormal model.
AB  - We present an empirical study of methods for estimating the location parameter of
      the lognormal distribution. Our results identify the best order statistic to use,
      and indicate that using the best order statistic instead of the median may lead
      to less frequent incorrect rejection of the lognormal model, more accurate
      critical value estimates, and higher goodness-of-fit. Using simulation data, we
      constructed and compared two models for identifying the best order statistic, one
      based on conventional nonlinear regression and the other using a data
      mining/machine learning technique. Better surgical procedure time estimates may
      lead to improved surgical operations.

PMID- 15152975
TI  - A modeling framework for optimal long-term care insurance purchase decisions in
      retirement planning.
AB  - The level of need and costs of obtaining long-term care (LTC) during retired life
      require that planning for it is an integral part of retirement planning. In this
      paper, we divide retirement planning into two phases, pre-retirement and post
      retirement. On the basis of four interrelated models for health evolution, wealth
      evolution, LTC insurance premium and coverage, and LTC cost structure, a
      framework for optimal LTC insurance purchase decisions in the pre-retirement
      phase is developed. Optimal decisions are obtained by developing a trade-off
      between post-retirement LTC costs and LTC insurance premiums and coverage. Two
      way branching models are used to model stochastic health events and asset
      returns. The resulting optimization problem is formulated as a dynamic
      programming problem. We compare the optimal decision under two insurance purchase
      scenarios: one assumes that insurance is purchased for good and other assumes it
      may be purchased, relinquished and re-purchased. Sensitivity analysis is
      performed for the retirement age.

PMID- 15152976
TI  - Reallocation of beds to reduce waiting time for cardiac surgery.
AB  - Waiting times for cardiac surgery is a significant problem in the medical world.
      The fact that patients' length of stay varies considerably makes effective
      hospital operation a difficult job. This paper analyzes patients' length of stay
      in hospital wards following cardiac surgery. Three scenarios for hospital
      management are presented and evaluated using Markov chain theory and simulation
      experiments. The aim of our analyses is to examine unused bed capacity in
      hospital wards. This makes it possible to attain a more efficient allocation of
      hospital beds. The results presented in this paper provide useful insight into
      relationships between patients' length of stay, bed availability, and hospital
      waiting lists.

PMID- 15152977
TI  - Modeling the spread of annual influenza epidemics in the U.S.: the potential role
      of air travel.
AB  - The role of air travel in the global spread of influenza has been the subject of
      a significant body of research, but this question has yet to be explored within
      the U.S. The goal of this research is to explore whether knowledge of U.S. air
      travel patterns and volumes leads to better forecasting of epidemics. We report
      the results of a series of simulations for the 1998-1999 through 2000-2001
      influenza seasons using a standard compartmental model coupled with air
      transportation data. These preliminary results suggest that air travel may play
      an important role in the spread of annual influenza within the U.S., particularly
      in cities with large air travel volumes.

PMID- 15152979
TI  - A frontier analysis approach for benchmarking hospital performance in the
      treatment of acute myocardial infarction.
AB  - This paper uses a non-parametric frontier model and adaptations of the concepts
      of cross-efficiency and peer-appraisal to develop a formal methodology for
      benchmarking provider performance in the treatment of Acute Myocardial Infarction
      (AMI). Parameters used in the benchmarking process are the rates of proper
      recognition of indications of six standard treatment processes for AMI; the
      decision making units (DMUs) to be compared are the Medicare eligible hospitals
      of a particular state; the analysis produces an ordinal ranking of individual
      hospital performance scores. The cross-efficiency/peer-appraisal calculation
      process is constructed to accommodate DMUs that experience no patients in some of
      the treatment categories. While continuing to rate highly the performances of
      DMUs which are efficient in the Pareto-optimal sense, our model produces
      individual DMU performance scores that correlate significantly with good overall
      performance, as determined by a comparison of the sums of the individual DMU
      recognition rates for the six standard treatment processes. The methodology is
      applied to data collected from 107 state Medicare hospitals.

PMID- 15152978
TI  - Applying a mixed-integer program to model re-screening women who test positive
      for C. trachomatis infection.
AB  - We proposed a mixed-integer program to model the management of C. trachomatis
      infections in women visiting publicly funded family planning clinics. We intended
      to maximize the number of infected women cured of C. trachomatis infections. The
      model incorporated screening, re-screening, and treatment options for three age
      groups with respective age-specific C. trachomatis infection and re-infection
      rates, two possible test assays, and two possible treatments. Our results showed
      the total budget had a great impact on the optimal strategy incorporating
      screening coverage, test selection, and treatment. At any budget level, the
      strategy that used a relatively small per-patient budget increase to re-screen
      all women who tested positive 6 months earlier always resulted in curing more
      infected women and more cost-saving than the strategy that was optimal under the
      condition of not including a re-screening option.

PMID- 15152980
TI  - Operant discriminative learning and evidence of subtelencephalic plastic changes
      after long-term detelencephalation in pigeons.
AB  - We analyzed operant discrimination in detelencephalated pigeons and
      neuroanatomical substrates after long-term detelencephalation. In Experiment I,
      experimental pigeons with massive telencephalic ablation and control pigeons were
      conditioned to key peck for food. Successive discrimination was made under
      alternating red (variable-ratio reinforcement) and yellow (extinction) lights in
      one key of the chamber. These relations were interchanged during reversal
      discrimination. The sessions were run until steady-state rates were achieved.
      Experiment II analyzed the morphology of the nucleus rotundus and optic tectum in
      long-term detelencephalated and control birds, using a Kluver-Barrera staining
      and image analyzer system. Detelencephalated birds had more training sessions for
      response shaping and steady-state behavior (p < 0.001), higher red key peck rates
      during discrimination (p < 0.01), and reversal discrimination indexes around
      0.50. Morphometric analysis revealed a decreased number of neurons and increased
      vascularity, associated with increases in the perimeter (p < 0.001) in the
      nucleus rotundus. In the optic tectum, increases in the perimeter (p < 0.05)
      associated with disorganization in the layers arrangement were seen. The data
      indicate that telencephalic systems might have an essential function in reversal
      operant discrimination learning. The structural characteristics of
      subtelencephalic systems after long-term detelencephalation evidence plastic
      changes that might be related to functional mechanisms of learning and neural
      plasticity in pigeons.

PMID- 15152981
TI  - Changes in body temperature and sleep-wakefulness after intrapreoptic injection
      of methoxamine in rats.
AB  - Several pieces of evidence suggest that the noradrenergic afferents in the medial
      preoptic area produce sleep and hypothermia by acting on alphal adrenergic
      receptors. On the other hand, in a few studies monitoring body temperature with a
      rectal probe, preoptic injection of the alphal adrenergic agonist methoxamine
      produced contradictory changes in body temperature and sleep-wakefulness. Such
      contradictions call for the re-examination of methoxamine induced body
      temperature changes using a better technique like telemetric recording. In the
      present study, we monitored body temperature and sleep-wakefulness simultaneously
      after the micro-injection of 0.5, 1, and 2 micromol methoxamine, into the medial
      preoptic area of adult male Wistar rats. Methoxamine injection produced
      hypothermia but no major change in sleep-wakefulness during the 3 hours after
      drug injection, except for a short period (15 min) of sleep after 120 min of
      injection. A short period of wakefulness, coinciding with the maximum fall in
      body temperature (30 min after injection) occurred when methoxamine was
      administered at higher doses. The results of this study indicate that alphal
      adrenergic receptors participate in preoptically mediated thermoregulatory
      measures that reduce body temperature. Hypothermia induced by methoxamine might
      have masked the hypnogenic action of this drug.

PMID- 15152982
TI  - Reinstatement of morphine-induced conditioned place preference in mice by priming
      injections.
AB  - To construct a model of relapse of drug abuse in mice, the induction, we
      evaluated the extinction and reinstatement of morphine-induced place preference.
      In Experiment 1, we examined the effects of morphine (0, 2, 3, 5, 10, 20 and 40
      mg/kg) in the conditioned place preference (CPP) paradigm. Mice showed CPP with
      5, 10, 20 and 40 mg/kg. In Experiment 2, we evaluated the effects of two
      different extinction procedures. After conditioning with 40 mg/kg of morphine,
      the mice underwent daily extinction sessions of 60 or 15 min of duration. CPP was
      extinguished after seven and nine sessions, respectively. In Experiment 3, we
      tested the reinstating effects of several priming doses of morphine. Mice were
      conditioned with 40 mg/kg of morphine and underwent the daily 15 min extinction
      sessions until CPP was no longer evident. Then, the effects of morphine (0, 2, 3,
      5, 10, 20, 40 mg/kg, i.p.) were evaluated. CPP was reinstated by doses from 5
      mg/kg upward. The results show that morphine priming injections are effective in
      reactivating opiate-seeking behavior in mice, and thus, the CPP paradigm might be
      useful to investigate the mechanisms underlying relapse of drug abuse.

PMID- 15152983
TI  - Cerebellar and hippocampal activation during eyeblink conditioning depends on the
      experimental paradigm: a MEG study.
AB  - The cerebellum and the hippocampus are key structures for the acquisition of
      conditioned eyeblink responses. Whereas the cerebellum seems to be crucial for
      all types of eyeblink conditioning, the hippocampus appears to be involved only
      in complex types of learning. We conducted a differential conditioning study to
      explore the suitability of the design for magnetencephalography (MEG). In
      addition, we compared cerebellar and hippocampal activation during differential
      delay and trace conditioning. Comparable conditioning effects were seen in both
      conditions, but a greater resistance to extinction for trace conditioning. Brain
      activation differed between paradigms: delay conditioning provoked activation
      only in the cerebellum and trace conditioning only in the hippocampus. The
      results reflect differential brain activation patterns during the two types of
      eyeblink conditioning.

PMID- 15152984
TI  - Effects of early training and nicotine treatment on the performance of male NMRI
      mice in the water maze.
AB  - This research aimed to evaluate the effect of nicotine treatment and prior
      training on a spatial learning task in differently aged NMRI male mice. In a
      longitudinal study, mice were randomly assigned to one of 14 experimental groups
      receiving different combinations of chronically injected nicotine (0.35 mg/kg)
      administered for 10 days (5 days before and during 5 days acquisition of task) or
      control treatments and training in the water maze at different ages. The mice
      displayed shorter escape latencies when evaluated at 6 and 10 months than when
      tested in this task at 2 months for the first time, demonstrating that early
      training preserves performance in the water maze up to 8 months after the initial
      experience. Nicotine treatment did not significantly change performance in the
      water maze at any age tested. Early practice in a spatial reference memory task
      appears to have lasting consequences and can potentially contribute to preventing
      some age-related spatial learning deficits.

PMID- 15152985
TI  - Effect of donepezil on group II mGlu receptor agonist- or antagonist-induced
      amnesia on passive avoidance in mice.
AB  - We examined the effect of the acetylcholinesterase (AChE) inhibitor, donepezil
      hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist-
      or antagonist-induced amnesia in the step-through passive avoidance task in male
      mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a
      group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated
      the latency on the step-through task. The subcutaneous injection of DONP at dose
      of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia
      induced by DCG-IV and LY341495, whereas donepezil alone did not affect task
      latency. The results suggest that activation of group II mGlu receptors and
      disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor
      antagonist) have a negative action on step-through passive avoidance memory
      performance, and that group II mGlu receptors and ACh interact to modulate
      learning and memory function.

PMID- 15152986
TI  - Enhancement of latent inhibition by chronic mild stress in rats submitted to
      emotional response conditioning.
AB  - This work evaluated the influence of chronic mild stress on latent inhibition
      (LI) in rats, using a conditioned emotional response (CER) procedure. Rats were
      assigned to four groups: a non pre-exposed control group (NPC), a non pre-exposed
      stressed group (NPS), a pre-exposed control group (PC), and a pre-exposed
      stressed group (PS). Stressed animals were submitted to a chronic mild stress
      (CMS) regimen for three weeks. The off-baseline conditioned emotional response
      procedure had four phases: licking response training, tone-shock conditioning,
      retraining, and testing. Conditioning consisted of 2 tone (30 s) and shock (0.5
      s) associations. Tone-shock conditioning evidenced by NPS and NPC groups suggests
      that stress did not interfere with the expression of a conditioned emotional
      response. Pre-exposure was carried out using 6 tones (30 s) during 2 sessions
      before conditioning. Prior exposure to the tone resulted in a decrease in
      learning that was greater in stressed animals. The results indicate an increase
      in latent inhibition induced by chronic mild stress. Such LI potentiation after
      CMS may be related to dopamine (DA) neurotransmission reduction in the central
      nervous system.

PMID- 15152988
TI  - Intramolecular C-N bond formation reactions catalyzed by ruthenium porphyrins:
      amidation of sulfamate esters and aziridination of unsaturated sulfonamides.
AB  - Ruthenium porphyrins [Ru(F(20)-TPP)(CO)] (F(20)-TPP = 5,10,15,20
      tetrakis(pentafluorophenyl)porphyrinato dianion) and [Ru(Por*)(CO)] (Por =
      5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8
      dimethanoanthracen-9-yl]porphyrinato dianion) catalyzed intramolecular amidation
      of sulfamate esters p-X-C(6)H(4)(CH(2))(2)OSO(2)NH(2) (X = Cl, Me, MeO),
      XC(6)H(4)(CH(2))(3)OSO(2)NH(2) (X = p-F, p-MeO, m-MeO), and
      Ar(CH(2))(2)OSO(2)NH(2) (Ar = naphthalen-1-yl, naphthalen-2-yl) with PhI(OAc)(2)
      to afford the corresponding cyclic sulfamidates in up to 89% yield with up to
      100% substrate conversion; up to 88% ee was attained in the asymmetric
      intramolecular amidation catalyzed by [Ru(Por)(CO)]. Reaction of [Ru(F(20)
      TPP)(CO)] with PhI[double bond]NSO(2)OCH(2)CCl(3) (prepared by treating the
      sulfamate ester Cl(3)CCH(2)OSO(2)NH(2) with PhI(OAc)(2)) afforded a
      bis(imido)ruthenium(VI) porphyrin, [Ru(VI)(F(20)-TPP)(NSO(2)OCH(2)CCl(3))(2)], in
      60% yield. A mechanism involving reactive imido ruthenium porphyrin intermediate
      was proposed for the ruthenium porphyrin-catalyzed intramolecular amidation of
      sulfamate esters. Complex [Ru(F(20)-TPP)(CO)] is an active catalyst for
      intramolecular aziridination of unsaturated sulfonamides with PhI(OAc)(2),
      producing corresponding bicyclic aziridines in up to 87% yield with up to 100%
      substrate conversion and high turnover (up to 2014).

PMID- 15152987
TI  - Combinatorial chemistry: libraries from libraries, the art of the diversity
      oriented transformation of resin-bound peptides and chiral polyamides to low
      molecular weight acyclic and heterocyclic compounds.
AB  - Combinatorial chemistry has deeply impacted the drug discovery process by
      accelerating the synthesis and screening of large numbers of compounds having
      therapeutic and/or diagnostic potential. These techniques offer unique
      enhancement in the potential identification of new and/or therapeutic candidates.
      Our efforts over the past 10 years in the design and diversity-oriented synthesis
      of low molecular weight acyclic and heterocyclic combinatorial libraries derived
      from amino acids, peptides, and/or peptidomimetics are described. Employing a
      "toolbox" of various chemical transformations, including alkylation, oxidation,
      reduction, acylation, and the use of a variety of multifunctional reagents, the
      "libraries from libraries" concept has enabled the continued development of an
      ever-expanding, structurally varied series of organic chemical libraries.

PMID- 15152989
TI  - Stereoselective synthesis of a potent thrombin inhibitor by a novel P2-P3 lactone
      ring opening.
AB  - The concise synthesis of a potent thrombin inhibitor was accomplished by a mild
      lactone aminolysis between an orthogonally protected bis-benzylic amine and a
      diastereomerically pure lactone. The lactone was synthesized by the condensation
      of l-proline methyl ester with an enantiomerically pure hydroxy acid, which in
      turn was synthesized by a highly stereoselective (>500:1 er) and productive
      (100,000:1, S/C) enzymatic reduction of an alpha-ketoester. In addition, a second
      route to the enantiomerically pure lactone was accomplished by a
      diastereoselective ketoamide reduction.

PMID- 15152990
TI  - Nortricyclyl-norbornenyl cation system accessed by carbene fragmentation.
AB  - Fragmentation of nortricyclyloxychlorocarbene 5 in pentane occurs by an S(N)i
      like process which yields nortricyclyl chloride 3g. In more polar solvents,
      fragmentation leads to nortricyclyl cation chloride anion pairs (9) that give
      mainly 3g, accompanied by approximately 10% of exo-2-norbornenyl chloride 4g.
      From exo-2-norbornenyloxychlorocarbene 6 in hydrocarbon solvents, "S(N)i"
      reactions lead mainly to exo- (4g) and endo-2-chloro-5-norbornenes (4g'). Leakage
      to ion pairs adds approximately 16% of nortricyclyl chloride 3g. In more polar
      solvents, the main product remains chloride 4g, but increasing quantities of 3g
      appear due to enhanced participation of ion pairs. Fragmentations of 5 and 6 in
      MeOH afford chlorides 3g and 4g as well as the corresponding methyl ethers 3b and
      4b. Nortricyclyl cation and norbornenyl cation chloride anion pairs and methanol
      solvated nortricyclyl cations are invoked to rationalize the results.

PMID- 15152991
TI  - Theoretical study of the vinyl allene oxide to cyclopent-2-en-1-one
      rearrangement: mechanism, torquoselectivity and solvent effects.
AB  - Density-functional calculations in the gas phase and solvent (PCM) at the B3LYP/6
      311++G(3df,2p)//B3LYP/6-31++G(d,p) level were performed to study a series of six
      reactions that involve the rearrangement of vinyl allene oxides to cyclopent-2-en
      1-ones along two distinct mechanistic pathways, namely concerted and stepwise.
      Calculations predict that stepwise pathways are highly competitive processes that
      occur via biradical/zwitterionic intermediates. Torquoselectivity is predicted to
      result from the concerted pathway leading to a stereodefined 4,5-disubstituted
      cyclopent-2-en-1-ones that should have memory of the starting terminal double
      bond geometry and oxide configuration. The stepwise pathway cannot show
      torquoselectivity as cyclization of the planar oxidopentadienyl zwitterion can
      follow enantiomorphous conrotations. The concerted/stepwise mechanistic
      preference depends mainly on the olefin geometry and is further modulated by
      epoxide substitution. The influence of the solvent (PCM model for dichloromethane
      or water) is moderate, although the greater (de)stabilization of the polarized
      oxidopentadienyl zwitterions along the stepwise mechanism does alter the kinetic
      preferences exhibited by the systems in vacuo. Results with system 1e suggest
      that, if vinyl allene oxide II having a double bond with Z-geometry, an
      intermediate in the biogenesis of epi-jasmonic acid IV, is processed along an in
      stepwise mechanism following ring opening, the enzyme allene oxide cyclase must
      enforce enantiofacial torquoselectivity.

PMID- 15152992
TI  - Stereoelectronic effects in ring-chain tautomerism of 1,3-diarylnaphth[1,2
      e][1,3]oxazines and 3-alkyl-1-arylnaphth[1,2-e][1,3]oxazines.
AB  - The disubstitution effects of X and Y in 1-(Y-phenyl)-3-(X-phenyl)-2,3-dihydro-1H
      naphth[1,2-e][1,3]oxazines on the ring-chain tautomerism, the delocalization of
      the nitrogen lone pair (anomeric effect), and the (13)C NMR chemical shifts were
      analyzed by using multiple linear regression analysis. Study of the three
      component equilibrium B<==>A<==>C revealed that the chain<==>trans (A<==>B)
      equilibrium constants are significantly influenced by the inductive effect
      (sigma(F)) of substituent Y on the 1-phenyl ring. In contrast, no significant
      substituent dependence on Y was observed for the chain<==>cis (A<==>C)
      equilibrium. There was an analogous dependence for the epimerization (C<==>B)
      constants of 1-(Y-phenyl)-3-alkyl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines. With
      these model compounds, significant overlapping energies of the nitrogen lone pair
      was observed by NBO analysis in the trans forms B (to sigma*(C1-C1'), sigma*(C1
      C10b), and sigma*(C3-O4)) and in the cis forms C (to sigma*(C1-H), sigma*(C1
      C10b), and sigma*(C3-O4)). The effects of disubstitution revealed some
      characteristic differences between the cis and trans isomers. However, the
      results do not suggest that the anomeric effect predominates in the preponderance
      of the trans over the cis isomer. When the (13)C chemical shift changes induced
      by substituents X and Y (SCS) were subjected to multiple linear regression
      analysis, negative rho(F)(Y) and rho(F)(X) values were observed at C-1 and C-3
      for both the cis and trans isomers. In contrast, the positive rho(R)(Y) values at
      C-1 and the negative rho(R)(X) values at C-3 observed indicated the contribution
      of resonance structures f (rho(R) > 0) and g (rho(R) < 0), respectively. The
      classical double bond-no-bond resonance structures proved useful in explaining
      the substituent sensitivities of the donation energies and the behavior of the
      SCS values.

PMID- 15152993
TI  - Binding of acetylcholine and tetramethylammonium to flexible cyclophane
      receptors: improving on binding ability by optimizing host's geometry.
AB  - The structure of a cyclophanic tetraester (1), previously employed for
      investigations on the cation-pi interaction, has been optimized to better
      accommodate acetylcholine (ACh) and tetramethylammonium (TMA) guests. Following
      indications from molecular modeling calculations, a flexible cyclophane receptor
      of significantly improved binding properties has been obtained by removing the
      four carbonyl groups of the parent host. 2,11,20,29
      Tetraoxa[3.3.3.3]paracyclophane (2) was prepared by an improved procedure, which
      was conveniently devised to avoid the formation of contiguous cyclooligomers that
      caused serious separation issues. Association of 2 with TMA picrate was measured
      in CDCl(3) at T = 296 K by (1)H NMR titrations and compared to binding data
      obtained for a set of reference hosts, including the parent tetraester 1, the
      corresponding cyclophanic tetraamine, the open-chain counterpart of 2, and its
      cyclooligomers from pentamer to octamer. Binding enhancements ranging from 15
      fold (with respect to the tetraester and the tetraamine) to over 80-fold (with
      respect to the open-chain tetraether) were achieved by geometry optimization of
      the host. Binding of 2 to ACh and TMA was investigated for a variety of
      counterions. A constant binding free energy increment of nearly 8 kJ mol(-1) with
      respect to 1 was observed, independent from the anion and irrespective of the
      different structure of the cationic guests. Results showed that the electrostatic
      inhibiting contribution of the counterion to the cation's binding is a
      characteristic constant of each anion. The value of -Delta G degrees = 44.9 kJ
      mol(-1) extrapolated for TMA in the absence of a counterion indicates that 28-34
      kJ mol(-1) of binding free energy are lost in ion pairing.

PMID- 15152994
TI  - Synthesis of cyclic peptidosulfonamides by ring-closing metathesis.
AB  - N-Protected beta-aminoethanesulfonyl chlorides (2a-e) were used in the
      preparation of sulfonamides 4, 8, 11a-c, and 15. Ring-closing metathesis of
      sulfonamides 4 and 8 did not lead to the expected nine-membered cyclic
      peptidosulfonamides. In contrast, the allylated peptidosulfonamides 11a-c and 15
      turned out to be suitable precursor systems for ring-closing metathesis using
      second-generation Grubbs catalyst and nine-membered cyclic peptidosulfonamides
      were obtained in 47-60% yields. The possibility for incorporation of these cyclic
      peptidosulfonamides into a peptide sequence was illustrated by the incorporation
      of an amino acid on the "S"- or "N"-terminus leading to 16 and 18-20,
      respectively. A model of cyclic peptidosulfonamide 16 hints at an extended-like
      structure.

PMID- 15152995
TI  - Efficient functionalization of aromatic C-H bonds catalyzed by gold(III) under
      mild and solvent-free conditions.
AB  - A gold(III)-catalyzed carbon-carbon bond formation reaction between arenes and
      electron-deficient alkynes or alkenes is described. Electron-rich arenes can be
      efficiently functionalized with the alkyne or alkene substrates. This reaction
      can be run with neat reactants at ambient temperature. Under the "solventless"
      conditions, clean product was obtained from a reaction of equal molar amounts of
      arene and alkyne substrates. The mild conditions and potential tolerance to
      different functional groups make this method practical for arene
      functionalization and for constructing complicated molecules. Efficient
      preparation of various coumarins from aryl alkynoates was demonstrated.
      Preliminary mechanistic studies were performed to probe the pathway of this
      reaction.

PMID- 15152996
TI  - Synthesis of highly branched sulfur-nitrogen heterocycles by cascade
      cycloadditions of [1,2]dithiolo[1,4]thiazines and [1,2]dithiolopyrroles.
AB  - We report the synthesis of some new polysulfur-nitrogen heterocycles by cascade
      cycloadditions to readily available polycyclic 1,2-dithiole-3-thiones. Thus,
      treatment of bis[1,2]dithiolopyrrole dithione 1 with dimethyl
      acetylenedicarboxylate (DMAD) or dibenzoylacetylene (DBA) gave the 1:4 adducts
      2a,b and 3a. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine
      dithiones 4a-d with the same dipolarophiles gave the 1:2, 1:3, or 1:4 adducts 5a
      c, 6a, 7a, 8a, 9a, and 10a,c,d selectively in fair to high yields. Reaction
      conditions were crucial for achievement of selectivity in thermal reactions.
      Catalysis by scandium triflate was used in the reaction of 4a and 2 equiv of
      DMAD. Treatment of the [1,2]dithiolo[1,4]thiazine dithione 11 with DBA gave the
      1:2, 1:3 (two isomers), and 1:4 adducts 12-14 and 15a-d selectively. Cyclic
      voltammetry of selected examples showed irreversible processes that were not
      influenced by peripheral groups bonded to the heterocyclic system.

PMID- 15152997
TI  - Theoretical investigation of the origins of catalysis of a retro-Diels-Alder
      reaction by antibody 10F11.
AB  - The antibody 10F11 catalyzes a retro-Diels-Alder reaction that forms HNO.
      Deductions about the mechanism of catalysis were made by Reymond, Baumann et al.
      from X-ray crystal structures and from kinetic measurements for mutated
      antibodies. We report a study of these reactions with quantum mechanical methods
      and a study of the substrate and transition state binding to the active site of
      the antibody 10F11 using density functional theory and empirical docking methods.
      We have quantitated the likely contributions to catalysis of three residues
      identified as possible causes of catalysis: Trp H104, Phe H101, and Ser H100. Trp
      H104 can make a significant contribution to catalysis through dispersive
      interactions (pi-stacking aromatic-aromatic stabilization). On its own, Phe H101
      makes only a small contribution to catalysis. When both aromatic residues are
      present, they act cooperatively and can make greater contributions to catalysis
      than expected for each residue alone. Ser H100 and the backbone NH of Phe H101
      are expected to act through hydrogen bonding to speed up the reaction, but our
      calculations suggest that they make only a small contribution to catalysis.
      Reymond's studies suggest that the hydrogen-bonding network may be mediated
      through a water molecule in the binding site.

PMID- 15152998
TI  - Mechanism of beta-silyl diacyl peroxide decomposition: a mild and stereoselective
      synthesis of beta-silyl esters.
AB  - A novel method for the formation of beta-silyl esters is presented. Mechanistic
      studies were carried out on the formation and decomposition of beta-silyl diacyl
      peroxides, showing that the decomposition pathway involves an ionic mechanism
      that is influenced by the presence of the beta-silyl moiety. These studies
      exclude a free radical decomposition pathway as evidenced by the absence of
      chemically induced dynamic nuclear polarization (CIDNP) during the reaction and a
      strong correlation of the resulting regioisomeric product distribution to
      sigma(+). This reaction allows for the formation of beta-silyl esters in 45-50%
      isolated yield with predictable regioselectivity and good to excellent
      diastereoselectivity. Studies demonstrate that ester products which are formed at
      benzylic centers have the erythro configuration, whereas ester products formed at
      alkyl centers have the threo configuration.

PMID- 15153000
TI  - Syntheses and base-pairing properties of locked nucleic acid nucleotides
      containing hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases.
AB  - Second generation 2'-O,4'-C-methylene-linked nucleotides 1-3 containing
      hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases were synthesized
      and incorporated into locked nucleic acid (LNA) oligonucleotides by means of the
      automated phosphoramidite method. The required phosphoramidite monomeric units
      were efficiently prepared via convergent synthesis. The glycosyl donor 4 was
      stereoselectively coupled with hypoxanthine and 6-chloro-2-aminopurine to give
      the 4'-C-branched nucleosides 5 and 17. The methods for conversion of 5 and 17
      into phosphoramidites 11, 25, and 29 were developed and described in full details
      for the first time. Hybridization properties of LNA octamers containing the new
      LNA nucleotides were assessed against perfect and singly mismatched DNA. The
      binding studies revealed that all LNA octamers hybridize very efficiently to DNA
      following Watson-Crick base-pairing rules with increased binding affinity
      compared to the DNA analogues. The unique properties of the nucleotides 1-3 make
      them very useful for further strengthening of the LNA technology.

PMID- 15152999
TI  - Swallowtail porphyrins: synthesis, characterization and incorporation into
      porphyrin dyads.
AB  - The incorporation of symmetrically branched tridecyl ("swallowtail") substituents
      at the meso positions of porphyrins results in highly soluble building blocks.
      Synthetic routes have been investigated to obtain porphyrin building blocks
      bearing 1-4 swallowtail groups. Porphyrin dyads have been synthesized in which
      the zinc or free base (Fb) porphyrins are joined by a 4,4'-diphenylethyne linker
      and bear swallowtail (or n-pentyl) groups at the nonlinking meso positions. The
      swallowtail-substituted Zn(2)- and ZnFb-dyads are readily soluble in common
      organic solvents. Static absorption and fluorescence spectra and electrochemical
      data show that the presence of the swallowtail groups slightly raises the energy
      level of the filled a(2u)(pi) HOMO. EPR studies of the pi-cation radicals of the
      swallowtail porphyrins indicate that the torsional angle between the proton on
      the alkyl carbon and p-orbital on the meso carbon of the porphyrin is different
      from that of a porphyrin bearing linear pentyl groups. Regardless, the
      swallowtail substituents do not significantly affect the photophysical properties
      of the porphyrins or the electronic interactions between the porphyrins in the
      dyads. In particular, time-resolved spectroscopic studies indicate that facile
      excited-state energy transfer occurs in the ZnFb dyad, and EPR studies of the
      monocation radical of the Zn(2)-dyad show that interporphyrin ground-state hole
      transfer is rapid.

PMID- 15153001
TI  - Radical and palladium-catalyzed cyclizations to cyclobutenes: an entry to the BCD
      ring system of penitrem D.
AB  - A novel approach toward the synthesis of the BCD ring system of penitrem D is
      described. The strategy capitalizes on the fast cyclization rates of aryl
      radicals into cyclobutenes and allows access to a variety of fused tricyclic
      structures. Radical/polar crossover reactions of precursors 24-29 promoted by
      samarium diiodide in the presence of HMPA and acetone allow access to the fully
      functionalized BCD ring system of penitrem D. The stereochemical implications of
      these processes are evaluated, and a Pd-mediated cyclization approach toward the
      penitrems is also introduced.

PMID- 15153002
TI  - Electrooxidative coupling of furans and silyl enol ethers: application to the
      synthesis of annulated furans.
AB  - The preparation of annulated furan systems as key synthetic intermediates through
      the application of a two-step annulation involving an electrochemical ring
      closure between a furan and a silyl enol ether has been studied. The reaction was
      shown to be quite general for the formation of six-membered rings in good yields
      and was tolerant of a variety of different functional groups. The ring closure
      was highly stereoselective, leading to the formation of cis-fused systems. Cyclic
      voltammetry and probe molecules were used to gain mechanistic insight into the
      reaction. These studies suggested that the key ring closure involved an initial
      oxidation of the silyl enol ether to a radical cation followed by a furan
      terminated cyclization.

PMID- 15153004
TI  - Stereoselective synthesis of polyhydroxyl surfactants. Stereochemical influence
      on Langmuir monolayers.
AB  - Herein is described the synthesis of surfactants featuring polyhydroxylated head
      groups. Three head groups were prepared via consecutive stereoselective
      dihydroxylations of a diene. By coupling of these with lipophilic tail groups six
      novel surfactants have been prepared. The monolayers prepared from four of these
      have been investigated at the air-water interface. Significant differences were
      observed between monolayers consisting of enantiomerically pure surfactants
      contra racemates as well as between diastereomers.

PMID- 15153003
TI  - A new strategy toward indole alkaloids involving an intramolecular
      cycloaddition/rearrangement cascade.
AB  - The intramolecular Diels-Alder reaction between an amidofuran moiety tethered
      onto an indole component was examined as a strategy for the synthesis of
      Aspidosperma alkaloids. Furanyl carbamate 23 was acylated using the mixed
      anhydride 26 to provide amidofuran 22 in 68% yield. Further N-acylation of this
      indole furnished 27 in 88% yield. Cyclization precursors were prepared by
      removing the carbamate moiety followed by N-alkylation with the appropriate alkyl
      halides. Large substituent groups on the amido nitrogen atom causes the reactive
      s-trans conformation of the amidofuran to be more highly populated, thereby
      facilitating the Diels-Alder cycloaddition. The reaction requires the presence of
      an electron-withdrawing substituent on the indole nitrogen in order for the
      cycloaddition to proceed. Treatment of N-allyl-bromoenamide 48 with n
      Bu(3)SnH/AIBN preferentially led to the 6-endo trig cyclization product 50, with
      the best yield (91%) being obtained under high dilution conditions. The initially
      generated cyclohexenyl radical derived from 48 produces the pentacyclic
      heterocycle 50 by either a direct 6-endo trig cyclization or, alternatively, by a
      vinyl radical rearrangement pathway.

PMID- 15153006
TI  - Intramolecular Photocycloaddition of Unsaturated Isoquinuclidines. Synthesis of 2
      Azatetracyclo[4.0.0.(4,9)0(7,10)]decanes and 3
      Azatetracyclo[6.1.1.0.(2,7)0(5,9)]decanes.
AB  - 2-Azabicyclo[2.2.2]oct-5-enes bearing an endo alkenyl substituent were
      synthesized by Diels-Alder addition of methyl vinyl ketone to a 1,6
      dihydropyridine derived from methyl nicotinate. Although 1,5-dienes with this
      skeleton were unreactive under thermal conditions, they were photochemically
      reactive. Irradiation of these dienes through a Corex filter resulted in
      intramolecular [2 + 2] cycloaddition to give "parallel" and "crossed"
      photoadducts along with small amounts of a hexahydroisoquinoline. The latter is
      thought to represent leakage of a diradical intermediate responsible for the
      parallel photoadduct. The new 2-azatetracyclo[4.4.0.0.(4,9)0(7,10)]decane and 3
      azatetracyclo[6.1.1.0.(2,7)0(5,9)]decane structures formed in the photochemical
      reactions are thermally stable.

PMID- 15153005
TI  - Suzuki cross-coupling reactions of gamma-alkylidenebutenolides: application to
      the synthesis of vulpinic acid.
AB  - alpha-Hydroxy-gamma-alkylidenebutenolides were efficiently functionalized by
      Suzuki cross-coupling reactions via the corresponding enol triflates. The natural
      product vulpinic acid was prepared by this methodology.

PMID- 15153007
TI  - Solid-phase intramolecular N-acyliminium Pictet-Spengler reactions as crossroads
      to scaffold diversity.
AB  - A novel solid-phase intramolecular Pictet-Spengler reaction is presented. The
      approach utilizes masked aldehyde building blocks protected as their N-Boc-1,3
      oxazinanes for the clean generation of solid-supported aldehydes. When exposed to
      simple acidic treatment, the aldehyde functionality is rapidly released and
      becomes susceptible to nucleophilic attack from an amide nitrogen of the peptide
      backbone, which results in the formation of a highly reactive cyclic N
      acyliminium ion. Subsequently, a quantitative and highly stereoselective Pictet
      Spengler reaction takes place by attack of the indole from a neighboring
      tryptophan, thus appending two new N-fused rings to the indole moiety. Extension
      of this intramolecular reaction to substituted indoles, and other reactive
      heterocycles, such as furane and thiophenes, provides a convenient and rapid
      access to a range of pharmacologically interesting tri- and tetracyclic
      scaffolds. Finally, the reaction products may conveniently be released from the
      solid support (PEGA) by cleavage of the base-labile linker (HMBA).

PMID- 15153008
TI  - Asymmetric synthesis of cyclic alpha-amino phosphonates using masked oxo
      sulfinimines (N-sulfinyl imines).
AB  - Five-, six-, and seven-membered cyclic alpha-amino phosphonates, amino acid
      surrogates, are prepared in enantiomerically pure form via the highly
      diastereomeric addition of metal phosphonates to masked oxo sulfinimines.
      Hydrolysis of the resulting masked oxo alpha-amino phosphonates followed by
      reduction of the intermediate cyclic imino phosphonates affords the title
      compounds in good yield.

PMID- 15153009
TI  - A modular and concise total synthesis of (+/-)-daurichromenic acid and analogues.
AB  - A modular and concise total synthesis of (+/-)-daurichromenic acid has been
      accomplished in four steps from ethyl acetoacetate, ethyl crotonate, and
      trans,trans-farnesal. A series of analogues of this natural product, which has
      potent anti-HIV activity, were also prepared from ethyl or methyl acetoacetate
      and a series of readily available alpha,beta-unsaturated esters and aldehydes.

PMID- 15153010
TI  - Studies toward labeling cytisine with [11C]phosgene: rapid synthesis of a delta
      lactam involving a new chemoselective lithiation-annulation method.
AB  - With the aim of the radiolabeling of cytisine, a potent agonist of nicotinic
      receptors, with [(11)C]phosgene, the rapid synthesis of a lactam model of our
      target has been studied. The key step of the delta-lactam formation is a new
      chemoselective lithiation-annulation method, under high dilution, of a suitable
      piperidinylcarbamoyl chloride. This precursor was obtained from (2
      hydroxyethyl)piperidine in a linear synthetic sequence involving a Corey-Fuchs
      olefination of the corresponding aldehyde, followed by a selective reduction,
      using a diimide equivalent, of an iodoalkyne into a (Z)-iodopropene piperidine.
      This alkene served as main precursor to study the cyclization according to
      several procedures using phosgene as the required carbonylating reagent.

PMID- 15153011
TI  - Evidence of substituent-induced electronic interplay. Effect of the remote
      aromatic ring substituent of phenyl benzoates on the sensitivity of the carbonyl
      unit to electronic effects of phenyl or benzoyl ring substituents.
AB  - Carbonyl carbon (13)C NMR chemical shifts delta(C)(C[double bond]O) measured in
      this work for a wide set of substituted phenyl benzoates p-Y
      C(6)H(4)CO(2)C(6)H(4)-p-X (X = NO(2), CN, Cl, Br, H, Me, or MeO; Y = NO(2), Cl,
      H, Me, MeO, or NMe(2) ) have been used as a tool to study substituent effects on
      the carbonyl unit. The goal of the work was to study the cross-interaction
      between X and Y in that respect. Both the phenyl substituents X and the benzoyl
      substituents Y have a reverse effect on delta(C)(C[double bond]O). Electron
      withdrawing substituents cause shielding while electron-donating ones have an
      opposite influence, with both inductive and resonance effects being significant.
      The presence of cross-interaction between X and Y could be clearly verified.
      Electronic effects of the remote aromatic ring substituents systematically modify
      the sensitivity of the C[double bond]O group to the electronic effects of the
      phenyl or benzoyl ring substituents. Electron-withdrawing substituents in one
      ring decrease the sensitivity of delta(C)(C[double bond]O) to the substitution of
      another ring, while electron-donating substituents inversely affect the
      sensitivity. It is suggested that the results can be explained by substituent
      sensitive balance of the contributions of different resonance structures
      (electron delocalization, Scheme 1).

PMID- 15153012
TI  - Photostimulated reactions of vinyl phosphate esters with triorganostannides.
      evidence for an SRN1 vinylic mechanism.
AB  - Ketones are converted into vinyl diethyl phosphate esters (VinDEP), which under
      photostimulation reacted with sodium trimethylstannide (1) or sodium
      triphenylstannide (2) in liquid ammonia affording vinylstannanes via a vinylic
      S(RN)1 mechanism. Thus, (1-phenylvinyl)DEP (3), (3,4-dihydro-1-naphthyl)DEP (7),
      (3,4-dihydro-2-naphthyl)DEP (9), (E)-(1,2-diphenylvinyl)DEP (12), (E/Z)-(1-methyl
      2-phenylvinyl)DEP (14) and (E)-(1-phenyl-2-methylvinyl)DEP (16) react with 1 and
      2, under photostimulation, leading to the corresponding substitution products in
      good to excellent yields (45-89%). On the other hand, there is no reaction
      between (1-cyclohexenyl)DEP (5) or (1-benzylvinyl)DEP (18) with either 1 or 2,
      under similar conditions. These reactions appear to be strongly dependent on
      structural features of the vinyl phosphate since only conjugated vinyl phosphates
      afforded substitution products. These substitution reactions are completely
      regioselective and stereoconvergent. It seems to be the first example of a
      vinylic S(RN)1 process involving organotin anions as nucleophiles.

PMID- 15153013
TI  - Kinetics and mechanism of the addition of benzylamines to
      benzylidenediethylmalonates in acetonitrile.
AB  - Kinetic studies of the benzylamine additions to benzylidenediethylmalonates (BDM:
      YC(6)H(4)CH[double bond]C(COOEt)(2)) in acetonitrile at 20.0 degrees C are
      reported. The rates in acetonitrile are consistent with that expected from the
      through-conjugative electron-accepting power of the activating groups,
      (COOEt)(2). The sign and magnitude of the cross-interaction constant, rho(XY) = 
      0.45, are in general agreement with those for the single-step amine additions to
      activated olefins. The kinetic isotope effects (k(H)/k(D) > 1.0) measured with
      deuterated benzylamines (XC(6)H(4)CH(2)ND(2)) increase with a stronger electron
      acceptor substituent in benzylamines (partial differential sigma(X) > 0) and a
      stronger electron donor in the substrate (partial differential sigma(Y) < 0).
      These trends are the same as those found for benzylidene-1,3-indandiones but are
      exactly opposite to those for other activated olefin series, e.g., beta
      nitrostyrene. It has been shown that the former series are thermodynamically
      controlled, whereas the latter are intrinsically controlled with a relatively
      strong transition state imbalance. The activation parameters, Delta H(++) and
      Delta S(++), also support our proposed transition state involving concurrent
      C(alpha)-N and C(beta)-H bond formation with a four-membered cyclic structure.

PMID- 15153014
TI  - Asymmetric synthesis of axially chiral biaryls by nickel-catalyzed grignard cross
      coupling of dibenzothiophenes.
AB  - Catalytic asymmetric Grignard cross-coupling of 1,9-disubstituted
      dibenzothiophenes (6a-c) and dinaphthothiophene (6d) with aryl- and alkyl
      Grignard reagents (7) proceeded with high enantioselectivity (up to 95% ee) in
      the presence of a nickel catalyst (3-6 mol %) coordinated with 2
      diphenylphosphino-1,1'-binaphthyl (H-MOP) or oxazoline-phosphine ligand (i-Pr
      phox) in THF to give 2-mercapto-2'-substituted-1,1'-biphenyls (8a-c) and 2
      mercapto-2'-substituted-1,1'-binaphthyls (8d) in high yields. The mercapto group
      in the axially chiral cross-coupling products was converted into several
      functional groups by way of the methylsulfinyl group. The rate of flipping in
      dinaphthothiophene was measured by variable-temperature (31)P NMR analysis of
      methylphenylphosphinyldinaphthothiophene derivative (21).

PMID- 15153015
TI  - The regiochemistry of cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha
      sulfonyl-5-hexenyl radicals: procedures leading to regioselective syntheses of
      cyclic sulfones and sulfoxides.
AB  - A study of the cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha
      sulfonyl-5-hexenyl and 5-methyl-5-hexenyl radicals reveals a unique contrast in
      the mode of ring closure of the radicals. In the case of the 5-hexenyl radicals,
      the sulfinyl-substituted species displays unexpected regioselectivity relative to
      its analogues. Thus, while the alpha-S- and alpha-SO(2)-5-hexenyl radicals give
      measurable and increasing quantities of 6-endo product, the alpha-sulfinyl
      species cyclizes with high selectivity (95.5:4.5) via a 5-exo mode. By contrast,
      ring closure of the 5-methyl-5-hexenyl radicals is found to give substantially
      the 6-endo product in all cases. It is the alpha-sulfonyl-5-methyl-5-hexenyl
      radical that now exhibits high regioselectivity (97.5:2.5) for 6-endo closure: an
      illustration of the synthetic value of this observation is the independent
      synthesis of the model cyclohexyl sulfone 61 in high yield. It is found that ring
      closure under the conditions employed occurs irreversibly in all cases.

PMID- 15153016
TI  - New piperidine scaffolds via nucleophilic reactivity of (-)
      phenyloxazolopiperidine.
AB  - The present work illustrates the power of compound 2 as a chiral, nonracemic, and
      stable 2-piperideine (enamine) equivalent in the rapid and efficient construction
      of 3-substituted piperidines (carbon-carbon and carbon-sulfur bonds) such as 3
      spiropiperidines. This methodology offers a new route to such systems that could
      compete with previously reported strategies.

PMID- 15153017
TI  - Intramolecular dehydro Diels-Alder reactions of diarylacetylenes: switching
      between benzo[b]- and benzo[c]fluorenones as products by controlling the
      rearrangement of cyclic allene intermediates.
AB  - Thermal cyclization of 1-[2-(arylethynyl)phenyl]-3-trimethylsilylpropynones
      affords a mixture of benzo[b]fluorenones and benzo[c]fluorenones. The ratio of
      the two isomers can be efficiently varied between 100:0 and 0:100 by introducing
      substituents with appropriate electronic and steric properties on the aryl rings
      and using an appropriate solvent.

PMID- 15153018
TI  - Role of secondary structure in the asymmetric acylation reaction catalyzed by
      peptides based on chiral C alpha-tetrasubstituted alpha-amino acids.
AB  - In a recent series of papers, Miller and co-workers were able to show that His(pi
      Me)-based, terminally protected peptides are potent catalysts of the asymmetric
      acyl transfer reaction, useful for the kinetic resolution of alcohols. In a
      structure-supporting solvent, one of the most active compounds, an Aib-containing
      tetrapeptide, is folded in a doubly intramolecularly H-bonded beta-hairpin motif
      incorporating a type-II' beta-turn conformation. In this work, we have expanded
      the study of the Miller tetrapeptide by examining a set of analogues and shorter
      sequences (dipeptide amides), characterized by chiral C(alpha)-tetrasubstituted
      alpha-amino acids of diverging bulkiness and optical configuration. Peptide
      synthesis in solution, conformational analysis by FT-IR absorption and (1)H NMR
      techniques, and screening of catalytic activity as well have been performed. Our
      results confirm the close relationship between the beta-hairpin 3D-structure and
      the catalytic activity of the peptides. A tetrapeptide analogue slightly more
      selective than the Miller compound has been found. However, the terminally
      protected, industrially more appealing, dipeptide amides are poorly effective.

PMID- 15153019
TI  - Enantioselective total synthesis of (+)-brefeldin A and 7-epi-brefeldin A.
AB  - A convergent enantioselective route to brefeldin A (BFA) and 7-epi-BFA was
      developed. The key C-4/C-5 chiral centers were established by using chiral
      auxiliary induced intermolecular asymmetric aldolization in the presence of
      TiCl(4) and TMEDA. The results with the thiazolidinethione/TiCl(4) mediated
      intermolecular asymmetric aldolization added some new information about the scope
      and limitations to the existing knowledge of that type of reactions (which so far
      was essentially limited to the reactions with N-propionyl thiazolidinethiones).
      During the course a method for protecting the liable aldol hydroxyl groups by
      using inexpensive TBSCl in DMF with 2,6-lutidine as the base was developed to
      replace the otherwise unavoidable TBSOTf procedure. Due to the excessive steric
      hindrance, removal of the auxiliary was much more difficult than most literature
      cases. Cleavage of the oxazolidinone by reduction was almost impossible. The
      thiazolidinethione auxiliary was relatively easier to remove. However, several
      reactions reported for facile removal of thiazolidinethione auxiliaries in the
      literature still failed. Reductive removal of the thiazolidinethione auxiliary
      was most effectively realized with LiBH(4) in diethyl ether in the presence of 1
      equiv of MeOH (a modification of a literature procedure for removal of
      oxazolidinone auxiliaries in less hindered substrates). Apart from the auxiliary
      removal, oxidation of the alcohol into aldehyde and the deprotection of the
      dithiolane protecting group were also rather difficult in the present context. A
      range of methods were screened before final solutions were found. The five
      membered ring was constructed by employing an intramolecular Mukaiyama reaction
      after many attempts with the intramolecular aldolization under a variety of
      conditions failed. The rate of elimination of the alkoxyl to form the alpha,beta
      double bond of the key intermediate cyclopentenone 49 with DBU was highly solvent
      dependent (very sluggish in CH(2)Cl(2) but rather fast in MeOH). Introduction of
      the lower chain (which was synthesized by using a Jacobsen KHR to establish the C
      15 chirality) was achieved through a Michael addition similar to the precedents
      in the literature. It has not been noticed before that the yield of this Michael
      reaction could be dramatically raised by using 3 equiv of the copper-lithium
      reagent 55. Reduction of the C-7 carbonyl was apparently more difficult than
      similar cases in the literature. After examination of many reagents under various
      conditions, it was found that the best reagent for yielding the alpha-isomer was
      (S)-2-methyl-CBS-borolidine/BH(3) and that for the beta-isomer was L-Selectride.
      The alpha- and beta-isomers were then further elaborated into (+)-brefeldin A and
      7-epi-BFA, respectively. An unexpected yet very interesting solubility difference
      between BFA and 7-epi-BFA was also observed.

PMID- 15153020
TI  - Do the electronic effects of sulfur indeed control the pi-selectivity of gamma
      sulfenyl Enones? An investigation.
AB  - The electronic effects of sulfur in gamma-sulfenyl enones are not transmitted to
      the carbonyl carbon through the pi bond as reported previously. The
      diastereoselectivity is rather controlled by a combination of several other
      factors. The steric effects arising from the substituents on the sulfur atom and
      the gamma-carbon and the bulk of the nucleophile constitute the major control
      elements.

PMID- 15153021
TI  - Enantiodivergent synthesis of pyrrolo[2,1-a]isoquinolines based on
      diastereoselective Parham cyclization and alpha-amidoalkylation reactions.
AB  - Enantiodivergent synthesis of C-10b-substituted pyrrolo[2,1-a]isoquinolines
      starting from an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3
      dicarboxyimide 3a, with a 2-exo-hydroxy-10-bornylsulfinyl group as a chiral
      auxiliary, has been developed. The key transformations are derived from
      diastereoselective intramolecular cyclization of aryllithiums and alpha
      amidoalkylation reactions, with the ethylidene bridge of the norbornene moiety
      dictating the stereochemical outcome in both types of reactions. Thus, the
      organolithium addition-intramolecular alpha-amidoalkylation sequence on imide 3a
      afforded stereoselectively the R configuration at C-12b, whereas the tandem
      Parham cyclization-intermolecular alpha-amidoalkylation reactions on the
      corresponding iodinated imide 3b occurred with complete control of
      stereoselectivity, leading to the epimer at C-12b. Subsequent reductive removal
      of the chiral auxiliary and retro-Diels-Alder reaction afforded (10bS)- and
      (10bR)-pyrroloisoquinolines 1 in high yields and optical purities (>99% ee).

PMID- 15153022
TI  - Anomalous intramolecular C-H insertion reactions of rhodium carbenoids: factors
      influencing the reaction course and mechanistic implications.
AB  - The intramolecular insertion of rhodium carbenoids into the alpha-C-H bonds of
      allylic ethers to give 3(2H)-furanones has been explored. Cyclopropanation is
      favored irrespective of the complex used for carbenoid generation or the
      substitution pattern of the allylic ether, unless a substituent is placed on the
      tether connecting the ether to the alpha-diazo ketone. Unusual acetal products
      resulting from an anomalous C-H insertion process are obtained in addition to the
      expected 3(2H)-furanones formed by conventional carbenoid C-H insertion. These
      acetals are the favored C-H insertion products in certain circumstances and
      particularly in cases where carbenoid generation is effected using an electron
      deficient rhodium complex. Experiments with simple deuterium labeled substrates
      reveal that anomalous C-H insertion products arise by a mechanism that is
      distinct from that leading to the formation of conventional C-H insertion
      products. The formation of acetal products and the outcome of reactions performed
      using deuterium-labeled substrates suggest that a mechanism involving hydride
      migration to the rhodium center of the carbenoid is operative.

PMID- 15153023
TI  - The nature of the micellar stern region as studied by reaction kinetics. 2.
AB  - The nature of rate-retarding effects of cationic micelles on the water-catalyzed
      hydrolyses of a series of para-substituted 1-benzoyl-1,2,4-triazoles (1a-f) and 1
      benzoyl-3-phenyl-1,2,4-triazole (2) has been studied using kinetic methods. A
      comparison is drawn between medium effects in the micellar Stern region and in
      model solutions for the micellar Stern region. Simple model solutions involving
      concentrated aqueous solutions of a small ionic molecule resembling the
      surfactant headgroup, as reported before,(1) were improved. New model solutions
      for alkyltrimethylammonium bromide micelles contain both tetramethylammonium
      bromide (TMAB), mimicking micellar headgroups, and 1-propanol, mimicking
      hydrophobic tails. The rate-retarding effect of micelles on the hydrolysis of 1a
      f and 2 is caused by the high concentration of headgroups as well as by
      hydrophobic tails in the Stern region where 1a-f and 2 bind to the micelle.
      Individual contributions of these interactions are quantified. Rate-retarding
      effects found for different probes, with different sensitivities for interactions
      as they occur when the probe binds to the micellar Stern region, as well as the
      micellar Stern region's micropolarity as reported by the E(T)(30) probe, are
      satisfactorily reproduced by new model solutions containing both TMAB and 1
      propanol.

PMID- 15153024
TI  - Synthesis of erythromycin derivatives via the olefin cross-metathesis reaction.
AB  - Olefin cross metathesis (CM) was applied to the synthesis of 6-O-substituted
      erythromycin derivatives. The reactions were catalyzed by transition metal
      alkylidene complexes, particularly bis(tricyclohexylphosphine)benzylidine
      ruthenium (IV) dichloride (Grubbs' first-generation catalyst). This approach
      allowed for the elaboration of the 6-O-allyl group of highly functionalized
      macrolides at various stages of the synthetic sequence, affording 6-O-3-aryl
      propenyl products with excellent E-selectivity. Little or no self-dimerization of
      the reacting components was found in the crude mixtures. Preliminary kinetic data
      accounts for the observed cross-selectivity based on substrate reactivity and
      steric factors.

PMID- 15153025
TI  - Stereoselective olefination of unfunctionalized ketones via ynolates.
AB  - Ynolates react with ketones at room temperature to afford alpha,beta,beta
      trisubstituted acrylates (tetrasubstituted olefins) with 2:1-8:1 geometrical
      selectivities. This can be regarded as a new olefination reaction of ketones
      giving tetrasubstituted olefins in good yield, even in the case of sterically
      hindered substrates. The reaction mechanism involves cycloaddition of ynolates
      with a carbonyl group and subsequent thermal electrocyclic ring-opening of the
      resulting beta-lactone enolates. The stereoselectivity is determined in the ring
      opening, which is regulated by torquoselectivity. In this paper, we describe the
      scope and limitations of olefination of ketones via ynolates and discuss the
      stereocontrol mechanism.

PMID- 15153026
TI  - Solution-phase synthesis of nucleobase-substituted analogues of triostin A.
AB  - A synthesis of novel analogues of triostin A presenting two identical or
      different nucleobases instead of the original quinoxaline substituents has been
      developed. The DNA bisintercalator triostin A (1) with its rigid backbone
      provides an optimal scaffold for a parallel preorganization of the intercalating
      moieties. The bicyclic octadepsipeptide is built up stepwise in solution and
      modified with various nucleobase-substituted acetic acids at a late stage. The
      choice of orthogonal protecting groups allows for the synthesis of triostin
      analogues bearing two different substituents.

PMID- 15153027
TI  - Synthesis and conformational evaluation of p-tert-butylthiacalix[4]arene-crowns.
AB  - Bridging of p-tert-butylthiacalix[4]arene afforded 1,3-dihydroxythiacalix[4]arene
      monocrown-5 (3b), 1,2-alternate thiacalix[4]arene-biscrown-4 and -5 (4a,b), and
      1,3-alternate thiacalix[4]arene-biscrown-5 and -6 (5a,b), depending on the metal
      carbonates and oligoethylene glycol ditosylates used. Starting from 1,3
      dialkylated thiacalix[4]arenes, the corresponding bridging reaction gave 1,3
      alternate, partial-cone, and cone conformers 10-19, depending on the substituents
      present. Temperature-dependent studies revealed that the conformationally
      flexible 1,3-dimethoxythiacalix[4]arene-crowns 10a-c exclusively occupy the 1,3
      alternate conformation. Demethylation exclusively gave the cone 1,3
      dihydroxythiacalix[4]arene-crowns (3a,c), which could not be obtained by direct
      bridging of thiacalix[4]arene. The different structures were assigned on the
      basis of several X-ray crystal structures and extensive 2-D (1)H NMR studies.

PMID- 15153028
TI  - Effects of amine nature and nonleaving group substituents on rate and mechanism
      in aminolyses of 2,4-dinitrophenyl X-substituted benzoates.
AB  - Second-order rate constants have been measured for the reactions of 2,4
      dinitrophenyl X-substituted benzoates (1a-f) with a series of primary amines in
      80 mol % H(2)O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Bronsted-type plot
      for the reactions of 1d with primary amines is biphasic with slopes beta(1) =
      0.36 at the high pK(a) region and beta(2) = 0.78 at the low pK(a) region and the
      curvature center at pK(a) degrees = 9.2, indicating that the reaction proceeds
      through an addition intermediate with a change in the rate-determining step as
      the basicity of amines increases. The corresponding Bronsted-type plot for the
      reactions with secondary amines is also biphasic with beta(1) = 0.34, beta(2) =
      0.74, and pK(a) degrees = 9.1, indicating that the effect of amine nature on the
      reaction mechanism and pK(a) degrees is insignificant. However, primary amines
      have been found to be less reactive than isobasic secondary amines. The
      microscopic rate constants associated with the aminolysis have revealed that the
      smaller k(1) for the reactions with primary amines is fully responsible for their
      lower reactivity. The electron-donating substituent in the nonleaving group
      exhibits a negative deviation from the Hammett plots for the reactions of 1a-f
      with primary and secondary amines, while the corresponding Yukawa-Tsuno plots are
      linear. The negative deviation has been ascribed to stabilization of the ground
      state of the substrate through resonance interaction between the electron
      donating substituent and the carbonyl functionality.

PMID- 15153029
TI  - Selective iron-catalyzed cross-coupling reactions of grignard reagents with enol
      triflates, acid chlorides, and dichloroarenes.
AB  - Cheap, readily available, air stable, nontoxic, and environmentally benign iron
      salts such as Fe(acac)(3) are excellent precatalysts for the cross-coupling of
      Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is
      shown that dichloroarene and -heteroarene derivatives as the substrates can be
      selectively monoalkylated by this method. All cross-coupling reactions proceed
      very rapidly under notably mild conditions and turned out to be compatible with a
      variety of functional groups in both reaction partners. A detailed analysis of
      the preparative results suggests that iron-catalyzed C-C bond formations can
      occur via different pathways. Thus, it is likely that reactions of
      methylmagnesium halides involve iron-ate complexes as the active components,
      whereas reactions of Grignard reagents with two or more carbon atoms are effected
      by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n)
      generated in situ. Control experiments using the ate-complex [Me(4)Fe]Li(2)
      corroborate this interpretation.

PMID- 15153030
TI  - Iron-catalyzed cross-coupling reactions. A scalable synthesis of the
      immunosuppressive agent FTY720.
AB  - A chemo- and regioselective cross-coupling reaction of the functionalized aryl
      triflate 5 with octylmagnesium bromide catalyzed by cheap, nontoxic, and
      environmentally benign Fe(acac)(3) sets the basis for a practical and scaleable
      synthesis of the octylbenzene derivative 6, which serves as a key building block
      for the preparation of FTY720 (1). This 2-amino-1,3-propanediol derivative shows
      highly promising immunosuppressive properties and is currently in human clinical
      phase III trials.

PMID- 15153031
TI  - Selective n,n-dibenzylation of primary aliphatic amines with dibenzyl carbonate
      in the presence of phosphonium salts.
AB  - In the presence of catalytic amounts of tetraalkylphosphonium salts and under
      solventless conditions, primary aliphatic amines (RNH(2): R = PhCH(2),
      Ph(CH(2))(2), n-decyl, and 1-naphthylmethyl) are efficiently N-benzylated to the
      corresponding RN(CH(2)Ph)(2), using dibenzyl carbonate as the benzylating
      reagent. Compared to the reaction run without salt, where the competitive
      formation of the benzyl carbamate is favored, the phosphonium salt promotes high
      selectivity toward the benzylated amine and an increase of the reaction rate as
      well. However, in a single case explored for an amino acidic compound, namely 4
      (aminomethyl)benzoic acid [4-(NH(2)CH(2))C(6)H(4)CO(2)H], both N,N-dibenzylation
      and esterification of the acid group were observed. Analysis of the IR
      vibrational modes of benzylamine in the presence of tetrabutylphosphonium bromide
      supports the hypothesis that this enhanced selectivity may be due to an acid-base
      interaction between the salt and the amine, which increases the steric bulk of
      the amine and favors attack of the nucleophile on the less hindered alkyl
      terminus of dibenzyl carbonate.

PMID- 15153032
TI  - Efficient palladium-catalyzed nucleophilic addition of triorganoindium reagents
      to carbocyclic derivatives.
AB  - Palladium (0)-catalyzed allylic substitution reactions employing triorganoindium
      reagents have been investigated. In situ generated vinyl- and arylindiums react
      with substituted and unsubstituted cyclohex-2-enyl esters in the presence of 1-3
      mol % Pd(2)(dba)(3) to produce vinyl- or arylcyclohexenes in moderate to
      excellent yields. The stereoselectivity of this process was also examined, and
      evidence is presented that the reaction proceeds with inversion of stereochemical
      configuration.

PMID- 15153033
TI  - A simple radical addition-elimination route to geometrically pure (E)-alkene and
      chromanone derivatives via beta-nitrostyrene.
AB  - Various geometrically pure (E)-beta-alkyl-styrenes have been synthesized by the
      radical NO(2) substitution of alkyl moieties generated via hydrogen abstraction
      followed by decarbonylation from aliphatic aldehydes. These reactions, which
      involve a high chemical selectivity and regioselectivity constitute a new route
      to (E)-beta-alkylstyrenes. Both aliphatic and aromatic aldehydes can be used in
      this novel reaction. When 2-allyloxybenzaldehyde was used, the benzoyl radical
      added directly to the double bond without decarbonylation to give the 3
      cinnamylchroman-4-one. This unique difference between aliphatic and aromatic
      aldehydes represents a simple route for the synthesis of biologically important
      chromanones.

PMID- 15153034
TI  - A concise asymmetric synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-yl Acetate
      and propionate, the sex pheromones of pine sawflies.
AB  - (2S,3S,7S)-3,7-Dimethylpentadecan-2-yl acetate (2) and its propionate analogue
      (3) are the main sex pheromones of all Neodiprion species and Diprion similes,
      respectively. Starting from (S)-malic acid and employing a highly chemo-, regio-,
      and stereoselective tandem ester reduction-epoxide formation-reductive epoxide
      opening reaction protocol, an efficient total synthesis of (2S,3S,7S)-2 and -3 is
      reported herein.

PMID- 15153035
TI  - Rapid stereoselective access to key pumiliotoxin precursors from a common
      intermediate.
AB  - Epoxidation and dihydroxylation of 8-methyl-2,3,6,8a-tetrahydro-1H-indolizin-5
      one proceeded from the concave face with good selectivity and gave advanced
      precursors for pumiliotoxin and allopumiliotoxin synthesis, respectively. The
      origin of the selectivity is believed to be stereoelectronic in nature and allows
      rapid entry to three different pumiliotoxin classes from a common intermediate.

PMID- 15153036
TI  - Artificial genetic systems: exploiting the "aromaticity" formalism to improve the
      tautomeric ratio for isoguanosine derivatives.
AB  - The tautomerism of 2'-deoxy-7-deaza-isoguanosine (2) was studied and compared to
      that of 2'-deoxyisoguanosine (1). The fixed (1)N-methyl (8) and O-methyl (4)
      derivatives were synthesized to represent the pure extremes of each tautomer. The
      replacement of the imidazole ring in 1 with a pyrrole ring in 2 makes the keto
      form in the latter more favored by 2 orders of magnitude (K(TAUT) for 2
      approximately 10(3), as opposed to K(TAUT) for 1 approximately 10).

PMID- 15153037
TI  - Endo-selective quenching of hexahydropyrrolo[2,3-b]indole-based N-acyliminium
      ions.
AB  - Radical decarboxylation of L-tryptophan-derived (2S,3aR,8aS)-8-arylsulfonyl-1,2
      di(methoxycarbonyl)-1,2,3,3a,8,8a-hexahydro-2H-pyrrolo[2,3-b]indoles 8 and 9 in
      the presence of diphenyl diselenide results in the endo-selective formation of
      (2R,3aR,8aS)-8-arylsulfonyl-1-methoxycarbonyl-2-phenylselenyl-1,2,3,3a,8,8a
      hexahydro-2H-pyrrolo[2,3-b]indoles 10 and 11. These selenides, in conjunction
      with Lewis acids, serves as precursors to the corresponding N-acyl iminium ions,
      which undergo selective endo-face quenching by allyltributylstannane,
      allyltrimethylsilane, propargyltrimethylsilane, and trimethylsilylcyanide.
      Stereochemical assignments rest on NMR data and crystallographic studies. The
      endo-selective nature of these reactions is interpreted in terms of minimization
      of allylic strain at the transition state for nucleophilic attack on the N-acyl
      iminum ion.

PMID- 15153038
TI  - A Highly Abbreviated Synthesis of Dibenzo[def,p]chrysene and Its 12-Methoxy
      Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate
      Carcinogens of Dibenzo[def,p]chrysene.
AB  - Dibenzo[def,p]chrysene (DBC) (1), is by far the most mutagenic and toxic
      polycyclic aromatic hydrocarbon identified. Its metabolic activation leads to
      trans-11,12-dihydroxy-11,12-dihydro-DBC (2), which is further metabolized to the
      ultimate metabolite, anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14
      tetrahydro-DBC (3), that binds to DNA causing mutations and ultimately tumor
      induction. We report a facile route for the syntheses of DBC (1) and its 12
      methoxy derivative (12-methoxy-DBC) (13), a key intermediate for the synthesis of
      2 and 3, using a Suzuki cross-coupling approach.

PMID- 15153039
TI  - Novel borane reduction of ether-protected aromatic lactams.
AB  - Borane reduction of ether-protected aromatic lactams produces 1-alkyl-1,2,3,4
      tetrahydroquinolines (5 and 6) in excellent yields. This reaction provides a
      novel one-pot tandem process for reduction of amide group and N-protected groups.
      Experimental results demonstrate that the reaction proceeds through two
      consecutive elimination and reductions via two C-O bond cleavages to form the
      foresaid products.

PMID- 15153040
TI  - Synthesis and characterization of pentaerythritol-derived oligoglycol and their
      application to catalytic Wittig-type reactions.
AB  - Several pentaerythritol-derived oligoglycols 1 with free hydroxyl groups are
      readily prepared by a convergent approach. Quantitative (13)C NMR proves to be an
      efficient tool for the characterization of oligoglycols. The corresponding
      telluride of oligoglycol 17 is synthesized and used as a good catalyst for Wittig
      type reactions in preparing both disubstituted and trisubstituted olefins in good
      to high yields.

PMID- 15153041
TI  - A facile access to chiral 4-isopropyl-, 4-benzyl-, and 4-phenyloxazolidine-2
      thione.
AB  - A highly practical procedure for preparing the chiral oxazolidine-2-thione
      auxiliaries using carbon disulfide and the corresponding chiral amino alcohols as
      the starting materials in the presence of potassium carbonate and hydrogen
      peroxide is presented.

PMID- 15153043
TI  - The MPEG effect: improving asymmetric processes by simple additives.
AB  - Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial
      effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes.
      The enantiomeric excesses of the products are improved, and this "MPEG effect"
      allows a reduction of the catalyst loading by a factor of 10.

PMID- 15153042
TI  - Preparation of carbocyclic S-adenosylazamethionine accompanied by a practical
      synthesis of (-)-aristeromycin.
AB  - For the preparation of a carbocyclic nitrogen analogue of S-adenosylmethionine
      (carba-AdoazaMet, 4), a practical synthesis of (-)-aristeromycin (7) has been
      developed using variations of literature procedures. This approach called for a
      stereospecific synthesis of (3aR,6aR)-2,2-dimethyl-3a,6a
      dihydrocyclopenta[1,3]dioxol-4-one ((4R, 5R)-4,5-O-isopropylidene-2
      cyclopentenone) (8), which was achieved by modifying reported procedures from D-(
      )-ribose.

PMID- 15153044
TI  - Efficient, "tin-free" radical cyclization to aromatic systems. synthesis of
      5,6,8,9,10,11-hexahydroindolo[2,1-a]isoquinolines.
AB  - Efficient radical cyclization of alkyl iodides to various aromatic systems
      including pyrrole, indole, isoquinolone, pyridone, and benzene, mediated by
      dicumyl peroxide, is described. The methodology was used to provide access to
      5,6,8,9,10,11-hexahydroindolo[2,1-a]isoquinoline derivatives.

PMID- 15153045
TI  - Iodine as a very powerful catalyst for three-component synthesis of protected
      homoallylic amines.
AB  - Iodine catalyzes efficiently the three-component condensation of aldehydes,
      benzyl carbamate, and allyltrimethylsilane to afford the corresponding protected
      homoallylic amines in excellent yields.

PMID- 15153046
TI  - Filling the GAPS: description and evaluation of a primary care intervention for
      children with chronic health conditions.
AB  - OBJECTIVES: Consistent with the "medical home" model, the GAPS program was
      developed to provide expanded care for children with a range of chronic health
      conditions within the context of primary care pediatric offices. Parents,
      pediatricians, and representatives from local Title V agencies participated to
      assess the child's and family's needs and to identify ways of addressing them.
      METHODS: Eleven pediatricians in 5 pediatric practices participated in the 4 main
      activities of the GAPS project: a) needs assessment; b) planning meeting among
      parents and pediatricians; c) practice-based advisory group; and d) Department of
      Public Health consultation. A telephone interview of parents and 2 needs
      assessment questionnaires completed by families were the 2 evaluation methods
      used. RESULTS: Parents were able to meet desires for "information" and "specific
      help." Moderate amounts of success were reported for meeting "contact" and
      "counseling" needs. Parents' explanations of unmet needs included lack of follow
      through in obtaining services, unavailability of services, change of mind
      regarding needs, and pragmatic barriers. Socioeconomic status, the diagnosis and
      severity of the child's condition, and maternal psychological status were not
      significant predictors of success in families' ability to get their needs met.
      CONCLUSIONS: Active collaboration among parents, pediatricians, and Department of
      Public Health staff helps to ensure comprehensive coordinated care for families
      of children with chronic health conditions. Considerable challenges remain in
      implementing effective medical homes.

PMID- 15153047
TI  - Potential cost savings of decreased emergency department visits through increased
      continuity in a pediatric medical home.
AB  - PURPOSE: To determine the potential cost savings of decreased emergency
      department (ED) visits resulting from increased continuity of care provided in a
      pediatric medical home. METHODS: An economic modeling study comparing the cost of
      ED visits associated with average continuity of care versus the cost of ED visits
      associated with a 10% point increase in continuity was performed. This model's
      premise is that increased continuity will decrease care in the ED. Parameters of
      the model included average continuity of care and expected use of the ED by
      pediatric patients as well as the relationship between these two variables.
      Parameters were estimated from the literature. Average continuity, as measured by
      the Continuity of Care Index by Bice and Boxerman, was determined to be 40%.
      Average ED use was estimated to be 0.68 visits/child per year. Continuity of care
      was stratified into low, medium, and high levels. The Medical University of South
      Carolina's ED charges were used. An average pediatric practice was estimated to
      contain 2000 patients. RESULTS: Two hypothetical practices of 2000 patients each
      were created to represent pediatric medical homes: practice 1 received 40%
      continuity and practice 2 received 50%. The model's outcome was measured in terms
      of expected ED charges per practice averted over a 1-year period. Increasing
      continuity of care by 10% points yielded a decline in expected ED visits from
      1362 to 1290 per practice: 19,905 US dollars was saved. CONCLUSION: Continuity of
      care can yield many benefits, including cost savings from decreased charges
      associated with less frequent ED use.

PMID- 15153048
TI  - Preparticipation physical evaluations for high school athletes: time for a new
      game plan.
AB  - For several decades, physicians have conducted preparticipation physical
      evaluations (PPEs) hoping to reduce the morbidity and mortality associated with
      high school sports. We argue in this Brief Commentary that the PPE as currently
      practiced is ineffective and illogical. We propose a research agenda that would
      provide data to more effectively promote adolescent health both on and off the
      playing field.

PMID- 15153050
TI  - Career opportunities available to graduates of pediatric residency programs.

PMID- 15153051
TI  - Can quality improvement reach into pockets of need for childhood immunizations?

PMID- 15153052
TI  - The epidemic of discontinuity in health care.

PMID- 15153053
TI  - Quality improvement in immunization delivery following an unsuccessful
      immunization recall.
AB  - OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a
      multifaceted quality improvement (QI) project to improve immunization (IZ) up-to
      date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed
      following QI. METHODS: A year-long QI project followed by a trial of
      reminder/recall. QI interventions were targeted at previously identified barriers
      to IZ and were designed specifically to improve the efficacy of reminder/recall.
      QI interventions were designed to 1) increase the use of medical record releases
      to document IZs received elsewhere; 2) improve the accuracy of parental contact
      information; and 3) reduce missed opportunities by utilizing chart prompts,
      provider education, and provider reminders. Following QI, we conducted a
      randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds
      increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18
      month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds
      18% before to 33% after (P <.001). After QI, an average of 61 records per month
      were updated with IZs received elsewhere. However, the accuracy of parental
      contact information worsened (29% unreachable before QI vs 44% after, P <.001)
      and missed opportunities did not improve (8% before vs 6% after, P = not
      significant [NS]). A subsequent trial of reminder/recall did not increase UTD
      rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS).
      CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged
      patient population. However, IZ reminder/recall did not further increase UTD
      rates above the rates achieved by the QI process.

PMID- 15153054
TI  - Breast milk feeding rates of mothers of multiples compared to mothers of
      singletons.
AB  - OBJECTIVE: Over 3% of infants born annually in the United States are from a
      multiple gestation pregnancy, yet there is little data published about the
      feeding practices of their mothers. The objectives of this study were to
      determine and compare the rates of breast milk feeding of mothers of multiples
      and mothers of singletons. METHODS: Stratified random sampling (n = 686) on the
      basis of plurality of pregnancy and gestational age at delivery was performed on
      a 1999 birth certificate database in the greater Cincinnati area. We collected
      information about infant feeding during the first 6 months of life using a
      retrospective, self-administered questionnaire and phone interview from mothers
      of term singletons (TS), preterm singletons (PS), term multiples (TM), and
      preterm multiples (PM). Data were analyzed using chi-square and logistic or
      multiple regression. RESULTS: We obtained feeding information from 346 mothers (n
      = 81 TS, 80 PS, 90 TM, and 95 PM). By 3 days postpartum, PM provided breast milk
      less often than all other groups: TS = 69%, PS = 66%, TM = 73%, PM = 57% (P
      =.035). Among mothers who initiated breast milk feeding, the geometric mean
      duration of at least some breast milk feeding was significantly shorter for PM
      than for all other groups: TS = 23 weeks, PS = 19 weeks, TM = 24 weeks, and PM =
      12 weeks (P =.002). CONCLUSIONS: Further evaluation of the potential causes for
      the lower breast milk feeding rates among PM is needed to develop effective
      intervention strategies and increase the number of preterm multiple gestation
      infants receiving breast milk.

PMID- 15153055
TI  - Early continuity of care and immunization coverage.
AB  - OBJECTIVE: We examined the relationship between early and exclusive continuity of
      care at the initial source of care and immunization coverage. METHODS: We used a
      cohort study design with 641 randomly selected children initiating care before 3
      months and making 2 or more visits to an inner-city practice network. We used 2
      complementary data sources: medical records and the New York City Department of
      Health Citywide Immunization Registry. Immunization measures were cumulative age
      appropriate and up-to-date at 18 months (UTD18). RESULTS: There was a gradual
      attrition from the initial source of care. By 18 months, less than half the
      children (46%) remained in care. Regardless of continuity, nearly half (42%) had
      used other immunization providers. The initial source of care contributed most
      immunizations (89%-94%); however, across all levels of continuity, children who
      also used other providers had higher immunization rates. We found a threshold
      effect of continuity beginning at 12 months: children in care from 12 to 14
      months were 17.5 times more likely to be UTD18 than those in care less than 6
      months. Each additional period in care increased the time remaining current with
      immunizations. Among children UTD18, 88% were in care at 11 months compared with
      38% among those not UTD18, a 50% difference. CONCLUSIONS: Continuity of care at
      the initial source of care had a significant and lasting impact on immunization
      coverage, even if not used exclusively. Interventions promoting continued use of
      the medical home over the first 2 years of life may help improve immunization
      coverage.

PMID- 15153056
TI  - Parents' mood and the content of pediatric care for young children.
AB  - OBJECTIVE: To assess the relationship between parents' mood and the provision of
      anticipatory guidance by pediatric health care providers. DATA SOURCE: Data
      analyzed were from the National Survey of Early Childhood Health, a cross
      sectional nationally representative survey concerning young children 4-35 months
      of age (n = 2068). KEY VARIABLES: Parents were asked whether the children's
      health care providers had discussed 10-12 age-appropriate health promotion topics
      and 5 psychosocial issues during the past 12 months. Parents also identified
      missed opportunities for guidance (ie, topics not discussed for which discussion
      would have been helpful) and reported whether providers should discuss
      psychosocial issues. Parents' mood was assessed using factor scores derived from
      the Mental Health Inventory. ANALYSES: Log-linear regression analyses determined
      if parents' mood was a significant predictor of the number of topics and issues
      discussed, the number of missed opportunities, and the reported number of issues
      that providers should discuss. RESULTS: Parents who were more often in a positive
      mood discussed more health promotion topics (B =.06, P <.001) and psychosocial
      issues (B =.10, P <.01) with their child's health care providers. Parents who
      were more often in a negative mood identified more missed opportunities (B =.08,
      P =.02) and more issues that providers should discuss (B =.04, P <.001).
      CONCLUSIONS: Increased attention to parents' mood and emotional well-being may
      help pediatricians identify parents who desire additional anticipatory guidance
      and ensure that opportunities for the provision of guidance are not inadvertently
      missed.

PMID- 15153057
TI  - Improving the interviewing and self-assessment skills of medical students: is it
      time to readopt videotaping as an educational tool?
AB  - PURPOSE: To evaluate the effect of a videotaping program on third-year medical
      students' interviewing and self-assessment skills. METHODS: A self-assessment
      manual, listing and explaining 21 core elements of the medical interview, was
      developed. After reading the manual, students videotaped an interview and self
      assessed their performances. Each student reviewed the videotape with a faculty
      member who also rated the performance. This process was repeated 1 week later.
      Changes in group performance, core element performance, and ability to self
      assess after the intervention were evaluated by Cohen d values to measure effect
      size, McNemar chi-square test for repeated measures, and concordance between
      faculty and student ratings. RESULTS: Sixty students participated in the
      videotaping study. Students inaccurately self-assessed on the first video 14% of
      the time. The 6 poorest-performed core elements were the least accurately self
      assessed. Lack of concordance between the global rating given by faculty and
      student identified all students with inflated self-assessment. One review session
      had a large effect on overall performance and interpersonal skills and a moderate
      effect on history-taking skills. A large effect on performance was seen for 3
      core elements, a moderate effect for 12 elements, and a small effect for the
      remaining 6 elements. Performance of the core elements that needed improvement
      did improve in 74% of the students (P <.001). Students' overall ability to self
      assess improved significantly (P <.01). CONCLUSIONS: Our videotaping program
      improved students' interviewing and self-assessment skills and identified
      students with inflated views of their abilities. Medical educators should re
      evaluate and readopt this excellent teaching and learning tool.

PMID- 15153058
TI  - Parent expectations and comfort with discussion of normal childhood sexuality and
      sexual abuse prevention during office visits.
AB  - BACKGROUND: The American Academy of Pediatrics recommends that pediatricians
      provide anticipatory guidance about sexual development and sexual abuse
      prevention. OBJECTIVE: To examine parents' expectations, comfort level, and
      experience discussing sexual development and sexual abuse prevention with
      pediatricians. METHODS: A consecutive sample of parents presenting for care at 9
      pediatric offices completed a self-administered survey. The survey included
      demographic information and questions related to parents' expectations, past
      experience, and comfort discussing normal childhood sexuality and sexual abuse
      prevention with their children's provider. Analyses examined relationships with
      parental recall of provider discussion about these topics and demographic
      characteristics. RESULTS: Of the 605 parents offered participation, 536 responses
      (89%) were analyzed. Respondents were 83% mothers, 62% white, 23% Hispanic, 7%
      African American, 6% Asian, 2% "other," and 65% college graduates. Nearly all
      respondents (98%) indicated pediatricians should discuss normal sexuality, and
      96% indicated physicians should discuss sexual abuse prevention. Most parents
      (77%) indicated both the parent and the doctor are responsible for introducing
      these topics. Over 90% of parents reported that they were comfortable discussing
      these topics. Only 45% of respondents reported their child's pediatrician had
      discussed normal sexuality, and 29% had discussed sexual abuse prevention.
      Logistic regression modeling found the highest rates of discussion for normal
      sexuality were among parents with older children and the highest rates of
      discussion for child sexual abuse prevention topics were for mothers and those
      with older children. CONCLUSIONS: Pediatricians can discuss normal sexuality and
      sexual abuse prevention without fear of alienating parents.

PMID- 15153059
TI  - When insurance status is not static: insurance transitions of low-income children
      and implications for health and health care.
AB  - OBJECTIVES: Among low-income children, to characterize the frequency of
      transitions in health insurance coverage and examine associations of transitions
      with health status and health care access. METHODS: Data from the 1999 National
      Survey of America's Families were used in weighted analyses to identify
      sociodemographic characteristics associated with health insurance transitions for
      children living in households with income <200% of the federal poverty level over
      the preceding 12 months. In logistic regression models, we examined associations
      of insurance transitions with children's health status (fair/poor health),
      postponement of children's medical care or prescription medications, and lack of
      physician visits. RESULTS: Among 27.93 million low-income children in 1999, 5.7
      million (20.4%) had experienced an insurance transition in the preceding year.
      Non-Hispanic black children (24.5%) and children whose parents did not have a
      partner or spouse (23.5%) were significantly more likely than other children to
      have experienced transitions. Hispanic children (16%) were least likely to have
      experienced transitions. Compared with children with continuous private coverage,
      children who had transitioned from public to private coverage were more likely to
      report fair or poor health, children who experienced transitions that included a
      period of no coverage were more likely to report postponed medical care and
      prescription drugs, and children who experienced a no-coverage-to-private
      coverage transition were more likely to have foregone physician visits.
      CONCLUSION: Transitions in insurance coverage affect many low-income children and
      may represent barriers to their health care. Considering insurance transitions
      may provide a more complete picture of children's health and health care
      utilization.

PMID- 15153060
TI  - Identification of resident and attending physicians: do parents know who is
      caring for their hospitalized child?
AB  - OBJECTIVE: Correct identification of a physician or resident is an essential
      first step in developing a good relationship between physicians, patients, and
      their families. However, many parents are unfamiliar with the individuals
      responsible for their children's care. This study was conducted to determine how
      often parents/guardians of hospitalized children could identify the residents and
      attending physicians caring for their children and what factors they considered
      important in physician identification. METHODS: This was a cross-sectional study
      with a convenience sample of the parents/guardians of hospitalized pediatric
      patients admitted to a university teaching hospital over a 2-month period; we
      used a self-administered, confidential questionnaire. RESULTS: Subjects were 144
      parents/guardians of hospitalized children (100% of subjects asked to
      participate, 19.3% of all hospitalized children); parents had the following
      characteristics: mean age, 30 years; 51% Caucasian, 43% African American; 82%
      female. Physician identification was 76% for attending physicians and 73% for
      residents. The factors rated as most important to parents were physician
      introduction (50%-76%), prior relationship (27%-13%), wearing of a white coat (2%
      8%), wearing of a name tag (4%-10%), and wearing of a stethoscope (0%-2%).
      Physician introduction was ranked higher for first hospitalizations. Subsequent
      hospitalizations increased identification of attending physicians but not
      residents. CONCLUSIONS: This study indicates that up to a quarter of parents
      could not identify the physician responsible for their children's care during a
      hospitalization. Improving physician identification may enhance other aspects of
      physician-family communication.

PMID- 15153061
TI  - Introduction: Definitions, measurements, and management in insomnia.

PMID- 15153062
TI  - Measuring treatment efficacy in insomnia.
AB  - The measurement of insomnia treatment efficacy has evolved over time.
      Historically, patient report measures were used to assess sleep the previous
      night, and, although important, these measures were not objectively validated.
      While the advent of polysomnography complemented patient reports of nocturnal
      sleep, few studies have evaluated daytime functioning and impact of impaired
      sleep on comorbid medical and psychiatric illnesses as measures of the efficacy
      of hypnotics. In the future, therapeutic endpoints will focus on important
      factors associated with insomnia, such as enhanced alertness, improved outcomes
      associated with augmentation therapy for depression, reduction in pain severity,
      and decreased sleep disturbances associated with hot flashes.

PMID- 15153064
TI  - The changing perspective on chronic insomnia management.
AB  - A particular challenge in the treatment of insomnia is management of chronic
      insomnia, which occurs in a substantial portion of the population. A number of
      factors suggest the importance of identifying this condition as distinct from
      short-term insomnia in clinical practice and treating these 2 entities
      differently. Yet, there is no consensus about how to make this distinction or how
      to manage patients beyond the short term. Clinicians have been without guidance
      as to how to address the significant challenges associated with treating patients
      long term with any of the currently available treatments. In recent years,
      however, new studies have suggested the emergence of a changing perspective on
      the management of chronic insomnia. These studies have begun to provide an
      empirical basis for making decisions in the treatment of patients with chronic
      insomnia. They suggest that clinical practice is evolving toward an improved
      capacity to treat insomnia, with treatments that can safely lead to sustained
      efficacy.

PMID- 15153063
TI  - Clinical and socioeconomic correlates of insomnia.
AB  - Insomnia is characterized by difficulty falling asleep (sleep onset disturbance),
      difficulty staying asleep (sleep maintenance disturbance), or poor quality
      (nonrestorative) sleep, leading to impairment of next-day functioning, including
      psychological distress. Published prevalence estimates of insomnia vary
      considerably, very likely due to differences in definitions, study setting, and
      data collection methods. However, estimates based on large population-based
      surveys provide a rather constant prevalence rate for chronic insomnia in the
      United States of about 10% (approximately 25 million people). Chronic insomnia is
      associated with numerous physical and psychiatric conditions and is more common
      in women and the elderly. Although it is often perceived as a symptom of
      depression, insomnia is also a precursor of depression and is associated with a
      substantial increase in the relative risk of major depression. Chronic insomnia
      is correlated with impaired mood, subjective functioning, and quality of life
      and, in some cases, with increased daytime sleepiness and accident risk. Those
      reporting insomnia have higher rates of absenteeism and health care utilization.
      Direct costs of insomnia have been estimated to be $13.9 billion annually, with a
      large majority of costs attributable to nursing home care. Chronic insomnia is a
      common problem, often associated with negative waking mood or function. As such,
      heightened clinical attention and clinical research appear warranted.

PMID- 15153065
TI  - Special considerations in insomnia diagnosis and management: depressed, elderly,
      and chronic pain populations.
AB  - Patients with insomnia who also have chronic pain or depression or who are
      elderly represent segments of the population that are particularly difficult to
      treat. These populations tend to be at higher risk for experiencing difficulty
      sleeping and are more likely to experience chronic insomnia, sleep maintenance
      problems, and/or nonrestorative sleep. Worsening insomnia may exacerbate other
      somatic and psychological symptoms and vice versa. Conversely, there is evidence
      that appropriate recognition and management of the sleep complaint may alleviate
      other symptoms related to the associated condition and help interrupt this
      vicious cycle.

PMID- 15153066
TI  - Classifying insomnia in a clinically useful way.
AB  - Insomnia is a prevalent complaint that may arise from myriad causes. Therefore,
      patients who present for insomnia evaluation and treatment represent a rather
      heterogeneous group that merits a reliable and valid diagnostic system. This
      review article considers the general purposes of diagnostic classification per se
      and highlights the factors that influence the development of diagnostic
      nosologies. Various past and current insomnia nosologies are described, and data
      supporting the reliability, validity, and general utility of these systems are
      presented. In addition, the limitations of existing nosologies are discussed, and
      factors that will lead to improved insomnia nosologies in the future are
      considered. The panel discussion that follows this review highlights the
      limitations of current nosologies and notes barriers that must be overcome to
      improve upon the currently available classification systems.

PMID- 15153067
TI  - Panel discussion: changing how we think about insomnia.

PMID- 15153069
TI  - Isolation and functional expression of human COQ2, a gene encoding a polyprenyl
      transferase involved in the synthesis of CoQ.
AB  - The COQ2 gene in Saccharomyces cerevisiae encodes a Coq2 (p
      hydroxybenzoate:polyprenyl transferase), which is required in the biosynthetic
      pathway of CoQ (ubiquinone). This enzyme catalyses the prenylation of p
      hydroxybenzoate with an all-trans polyprenyl group. We have isolated cDNA which
      we believe encodes the human homologue of COQ2 from a human muscle and liver cDNA
      library. The clone contained an open reading frame of length 1263 bp, which
      encodes a polypeptide that has sequence homology with the Coq2 homologues in
      yeast, bacteria and mammals. The human COQ2 gene, when expressed in yeast Coq2
      null mutant cells, rescued the growth of this yeast strain in the absence of a
      non-fermentable carbon source and restored CoQ biosynthesis. However, the rate of
      CoQ biosynthesis in the rescued cells was lower when compared with that in cells
      rescued with the yeast COQ2 gene. CoQ formed when cells were incubated with
      labelled decaprenyl pyrophosphate and nonaprenyl pyrophosphate, showing that the
      human enzyme is active and that it participates in the biosynthesis of CoQ.

PMID- 15153071
TI  - Glycoconjugate histochemistry of the seminal vesicles of the Japanese miniature
      (Shiba) goat.
AB  - The present study localizes and characterizes complex glycoconjugates in the
      seminal vesicles of the Japanese Shiba goat, using several carbohydrate
      histochemical procedures, including lectin techniques at light and electron
      microscopic levels. Glandular epithelial cells and luminal secretions were shown
      to contain neutral and acidic glycoconjugates with various saccharide residues,
      such as alpha-D-Man, alpha-D-Glc, alpha-L-Fuc, beta-D-Gal, GalNAc, GlcNAc, and
      NeuAc (sialic acid). The terminal oligosaccharide chains of sialoglycoconjugates
      present in the seminal vesicles were NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc
      alpha 2-3Gal beta 1-4GlcNAc. In addition, in lysosomes of the glandular
      epithelial cells alpha-D-Man, alpha-D-Glc, GlcNAc and NeuAc (sialic acid)
      residues could be detected, the secretory vesicles contained alpha-L-Fuc, and the
      endoplasmic reticulum exhibited alpha-D-Man and alpha-D-Glc residues. The complex
      glycoconjugates with various sugar residues found in the seminal vesicles of the
      goat may be involved in various fertilization-related events.

PMID- 15153070
TI  - A co-translational model to explain the in vivo import of proteins into HeLa cell
      mitochondria.
AB  - The dual signal approach, i.e. a mitochondrial signal at the N-terminus and an ER
      (endoplasmic reticulum) or a peroxisomal signal at the C-terminus of EGFP
      (enhanced green fluorescent protein), was employed in transfected HeLa cells to
      test for a co-translational import model. The signal peptide from OTC (ornithine
      transcarbamylase) or arginase II was fused to the N-terminus of EGFP, and an ER
      or peroxisomal signal was fused to its C-terminus. The rationale was that if the
      free preprotein remained in the cytosol, it could be distributed between the two
      organelles by using a post-translational pathway. The resulting fusion proteins
      were imported exclusively into mitochondria, suggesting that co-translational
      import occurred. Native preALDH (precursor of rat liver mitochondrial aldehyde
      dehydrogenase), preOTC and rhodanese, each with the addition of a C-terminal ER
      or peroxisomal signal, were also translocated only to the mitochondria, again
      showing that a co-translational import pathway exists for these native proteins.
      Import of preALDH(sp)-DHFR, a fusion protein consisting of the leader sequence
      (signal peptide) of preALDH fused to DHFR (dihydrofolate reductase), was studied
      in the presence of methotrexate, a substrate analogue for DHFR. It was found that
      70% of the preALDH(sp)-DHFR was imported into mitochondria in the presence of
      methotrexate, implying that 70% of the protein utilized the co-translational
      import pathway and 30% used the post-translational import pathway. Thus it
      appears that co-translational import is a major pathway for mitochondrial protein
      import. A model is proposed to explain how competition between binding factors
      could influence whether or not a cytosolic carrier protein, such as DHFR, uses
      the co- or post-translational import pathway.

PMID- 15153072
TI  - Sodium transport across the isolated epithelium of sheep omasum is influenced by
      luminal ammonia.
AB  - Ammonia is a physiological fermentation product in the forestomachs and is
      absorbed from the rumen and omasum. Cellular uptake of ammonia affects the
      intracellular pH of polar and non-polar cells. The effect of the uptake on the pH
      of the cytosol depends on the predominant form of ammonia. NH(3) uptake and its
      intracellular protonation tend to alkalinize the cytoplasm, whereas the uptake of
      NH(4)(+) acidifies the cytoplasm by reversing this reaction. Consequently, the
      absorption of ammonia across the omasal epithelium could cause a change of the
      intracellular pH and pH-dependent transport mechanisms like Na/H exchange.
      Because no information is available about the form of ammonia absorbed in the
      omasum and, hence, possible modulation of Na transport by ammonia, the effect of
      increasing luminal ammonia concentrations (0, 5, 15 and 30 mmol/l) on Na
      transport were studied. In epithelia of hay-fed animals, ammonia linearly
      inhibited Na transport in a dose-dependent manner, at a luminal pH of 7.40, but
      not at a pH of 6.40. Ammonia did not influence Na transport in epithelia of
      concentrate-fed animals. Because luminal ammonia did not consistently change the
      short circuit current or tissue conductance absorption of ammonia as NH(4)(+)
      appears to be unlikely. The predominant form of ammonia absorbed in the omasum is
      probably NH(3), which is protonated in the cytosol. The reduced availability of
      protons may be the cause of inhibition of Na transport via Na/H exchange.

PMID- 15153073
TI  - Effect of energy density in the diet and milking frequency on plasma metabolites
      and hormones in early lactation dairy cows.
AB  - The effects of energy density in the diet [low = 0.86 SFU/kg dry matter (DM) or
      high = 1.06 SFU/kg DM] and daily milking frequency (two or three times) in early
      lactation on plasma concentrations of metabolites and hormones were evaluated in
      40 Holstein dairy cows arranged in a 2 x 2 factorial block design. The four
      treatment combinations were L2, L3, H2 and H3, and the experimental period
      comprised the first 8 weeks of lactation. Plasma glucose, insulin and insulin
      like growth factor (IGF)-I concentrations were on average 8 (3.43 versus 3.19
      mmol/l), 114 (41.6 versus 19.4 pmol/l) and 60% (91.9 versus 57.4 ng/ml) higher,
      whereas beta-hydroxybutyrate (BOHB), plasma urea nitrogen (PUN) and growth
      hormone (GH) concentrations were on average 18 (0.73 versus 0.89 mmol/l), 14
      (7.18 versus 8.35 mmol/l), and 63% (1.0 versus 2.6 ng/ml) lower for cows fed diet
      H than for cows fed diet L. Cows milked three times daily had a 6% (3.20 versus
      3.42 mmol/l) lower plasma glucose concentration and a 19% (0.88 versus 0.74
      mmol/l) higher plasma concentration of BOHB compared with cows milked two times
      daily. Plasma non-esterified fatty acid (NEFA) concentration was not affected by
      either treatment. Overall, it is concluded that increasing the daily milking
      frequency creates a higher metabolic imbalance in early lactation. Cows in early
      lactation will benefit from receiving a high energy density diet and thereby
      avoid a too high metabolic imbalance when mobilizing body tissue in support of
      milk production.

PMID- 15153074
TI  - Histopathological effects of boldenone in cattle.
AB  - Histopathology of male cattle previously found positive for beta-boldenone in
      urine in the Netherlands and in Italy was studied. The animals were derived from
      practice and several weeks had passed after the finding of beta-boldenone before
      the animals were examined. The animals consisted of 34 male veal calves and one
      finishing bull. In the prostate gland hypersecretion, cyst formation (45%) and
      hyperplasia of the urethral epithelium was observed, in the bulbo-urethral gland
      similar alterations were present. The testis showed reduced development and
      degeneration of the germinal epithelium (70%), leading to debris and syncytial
      cell formation in the lumina. Stromal proliferation was evident. In some animals
      the liver was sampled and showed periportal fibrosis, bile duct proliferation and
      sometimes necrosis. The bull also showed degeneration of the germinal epithelium
      of the testis and absence of sperm production, the prostate gland showed some
      secretion and had an atrophic appearance. It is concluded that beta-boldenone may
      lead to degeneration of the germinal epithelium of the testis and hypersecretion
      and cyst formation in the prostate and bulbo-urethral gland, which alterations
      may heal in time.

PMID- 15153075
TI  - D-Lactic acidosis in calves as a consequence of experimentally induced ruminal
      acidosis.
AB  - In order to test the hypothesis that ruminal drinking in calves can lead to D
      lactic metabolic acidosis, ruminal acidosis was induced in nine calves by
      intraruminal application of untreated whole milk via a stomach tube. The amount
      of the daily force-fed liquid was 3 x 1 l. The experimental design called for an
      end of intraruminal applications if two or more of the following signs were
      observed: severe depression, estimated degree of dehydration >10%, absence of
      sucking reflex, lack of appetite for two consecutive feedings, severe metabolic
      acidosis with calculated Actual Base Excess (ABE) <-15 mmol/l. The procedure was
      scheduled to be discontinued on the 17th day of experiment. The onset of ruminal
      acidification occurred rapidly, and mean pH value fell from 6.70 (+/-0.48) to
      4.90 (+/-0.38) after the first application. The following days the pH values
      varied between 4 and 5. Rumen acidity was characterized biochemically by a
      significant increase in both isomers of lactic acid. The effects of the
      intraruminal administration on the calves were detrimental; eight of nine calves
      showed an acute disease process. According to the pre-established clinical
      standard, seven of nine calves were removed from the intraruminal feeding
      schedule. All but one of the calves developed severe systemic acidosis. The
      increase in anion gap demonstrated the net acid load. In all the calves D-lactate
      levels were found to show a significant and rapid increase. On the contrary, L
      lactate never deviated from physiological levels. These observations confirm
      that, in young calves as in adult cattle, ruminal acidosis may lead to a
      clinically manifested D-lactic metabolic acidosis.

PMID- 15153076
TI  - Effects of sarcoptic mange and its control with oil of Cedrus deodara, Pongamia
      glabra, Jatropha curcas and benzyl benzoate, both with and without ascorbic acid
      on growing sheep: epidemiology; assessment of clinical, haematological, cell
      mediated humoral immune responses and pathology.
AB  - The aim of this study was to evaluate the therapeutic efficacy of commonly used
      acaricidal drugs in India and also to assess the effect of ascorbic acid (AA) as
      adjunct therapy in 72 growing sheep with sarcoptic mange, aged 5-6 months and
      weighing 20.4-31.7 kg. Eight replicates of nine animals were formed based on sex,
      and day 0 body weight. Another set of 12 healthy sheep (5-6 months old)
      constituted the healthy control group. Drugs were applied locally on the affected
      parts daily and recovery changes in skin lesions were observed at the time of
      every application. L-Ascorbic acid was administered intramuscularly. Skin
      scrapings were collected daily from each group and examined for the presence of
      mites. Blood samples from each group were collected and analysed for total
      erythrocytes, leucocytes, haematocrit, haemoglobin and lymphocytes on 0, 14th and
      28th day post-treatment (PT). Cell-mediated (CMI) and humoral immune (HI)
      responses were assessed on 0 and 28 days PT. Within groups treated with the drug
      alone, recovery in oil of Jatropha curcas group was faster and lesions were free
      from mites after the eighth application. For each drug, the recovery was faster
      with AA as an adjunct therapy when compared with the group treated with the drug
      alone. Within all groups, recovery in oil of J. curcas plus ascorbic acid (OJC
      AA) group was fastest and the lesions were mite-free after three applications.
      The overall mean values were higher for all haematological parameters in OJC-AA
      group. Recovery with respect to suppressed CMI and HI responses during infection
      was also faster in this group. Gross and microscopic pathological studies
      revealed a marked adverse effect of infection on skin, kidney, spleen and liver.
      The OJC-AA group indicated faster recovery. It is concluded from this study that
      oil of J. curcas was found more efficacious in controlling sarcoptic mange in
      sheep and AA might be beneficial as adjunct in case of sarcoptic mange to get
      quick recovery with lesser applications of main therapy. However, the
      pharmacology of AA with reference to health of skin needs to be investigated.

PMID- 15153077
TI  - Effects of sarcoptic mange and its control with oil of Cedrus deodara, Pongamia
      glabra, Jatropha curcas and benzyl benzoate, both with and without ascorbic acid
      on growing sheep: assessment of weight gain, liver function, nutrient
      digestibility, wool production and meat quality.
AB  - The aim of this study was to evaluate the therapeutic efficacy of commonly used
      acaricidal drugs in India and also to assess the effect of ascorbic acid as
      adjunct therapy in 72 growing sheep with sarcoptic mange, aged 5-6 months and
      weighing 20.4-31.7 kg. Eight replicates of nine animals were formed based on sex,
      and day 0 body weight. Drugs were applied locally on the affected parts daily and
      recovery changes in skin lesions were observed at the time of every application.
      L-ascorbic acid was administered intramuscularly. Skin scrapings were collected
      daily from each group and examined for the presence of mites. Body weights were
      measured every 10th day from day 0 to 60. Nutrient digestiblity was evaluated by
      studying digestibility coefficients for dry matter, crude protein, ether extract,
      crude fibre, nitrogen free extract, total carbohydrates and nutrient balance
      (nitrogen, calcium and phosphorus) for a 30-day period. The liver function was
      evaluated by bromosulphophthalein (BSP) dye retention time. The animals were
      shorn on day 60 post-treatment (PT). Meat quality assesment was carried out by
      killing sheep at 60 days PT and estimating pH, water-holding capacity (WHC),
      tenderness, muscle colour, rib eye area and fat thickness. The lambs treated with
      oil of Jatropha curcas ascorbic acid had significantly (P < 0.05) greater mean
      daily body weight gains (63.29 g) than the infected untreated control (41.10 g).
      This was also higher than the mean daily weight gain in other treated groups.
      Infected untreated sheep showed significantly (P < 0.01) reduced digestibility
      coefficients for dry matter, crude protein, crude fibre, ether extract and total
      carbohydrate, but no significant differences for nitrogen-free extract. Treated
      sheep had significantly higher positive nitrogen, calcium and phosphorus balances
      compared with infested untreated sheep. Oil of J. curcas plus ascorbic acid (OJC
      AA) treated group was better over all other treated groups with respect to
      nutrient digestibility. The BSP test revealed significant (P < 0.05) increase in
      BSP retention time in sheep with sarcoptic mange. Post -treatment, the BSP
      retention time decreased in all treated groups and the decrease was maximum in
      OJC-AA treated group. The carcasses of sheep treated with OJC-AA had
      significantly (P < 0.01) higher water holding capacity, rib eye area and back fat
      thickness than the untreated infected control group. The muscle pH and tenderness
      values were significantly lower in OJC-AA treated group post-slaughter than
      infested untreated control group. Muscle colour of OJC-AA treated group was
      maximum bright red. The lambs treated with OJC-AA had significantly (P < 0.05)
      greater clean fleece weight and fleece yield than the untreated infected group.
      It is concluded that OJC was the better therapy for sarcoptic mange of sheep and
      ascorbic acid as adjunct therapy is advisable. OJC-AA therapy may be better from
      the point of view of improving two most important production parameters in sheep,
      that is, wool yield and meat production.

PMID- 15153078
TI  - Silymarin, a possible hepatoprotector in dairy cows: biochemical and histological
      observations.
AB  - Silymarin, a standardized extract from Silybum marianum seed, is a natural
      hepatoprotector used for the treatment of liver diseases in man. The aim of this
      study was to investigate its safety and efficacy in periparturient dairy cows.
      Ten treated and 10 control pregnant dairy cows were paired by parity, body
      condition score (BCS), health condition and previous milk production. Treatment
      consisted of daily 10 g per animal of silymarin extract administered as oral
      drenches, from 10 days prior to the calving date to 15 days after calving. Blood
      samples and liver biopsies were taken from each animal at 7 and 30 days after
      calving. Hepatic functions were evaluated by assay of plasma beta-hydroxybutyrate
      (BHBA), total cholesterol, high-density lipoproteins, low-density lipoproteins,
      triglyceride and total bilirubin. The histological aspect of the liver was
      assessed in biopsies. Clinical chemistry values were similar for both groups and
      effects at different times (day 7 versus day 30; P < 0.05) were attributed to
      physiological variations in periparturient cows. Histology showed fat
      accumulation in the liver of both groups, as it is expected in periparturient
      dairy cows. In treated cows, fat-rich hepatocytes were observed near the central
      vein. These observations suggest that, at the used dosage, S. marianum extract
      has no adverse effect on the liver of lactating cows, and presents no objective
      evidence for a hepatoprotective effect in this species.

PMID- 15153079
TI  - Hypothyroid goitre in a ram: chemical analysis gives indirect evidence for a
      structurally altered type of ovine thyroglobulin.
AB  - The thyroglobulin of a ram of the East Friesian milk sheep breed suffering from
      goitre was investigated by physico- and immunochemical methods. The respective
      ram was the only animal amongst the other sheep of the flock, that exhibited
      severe goitre, additionally showing depressed behaviour. Results of the thyroid
      stimulating hormone response test were indicative of hypothyroidism. The
      dysfunction of the thyroid gland could be treated by additional iodine
      supplementation quite successfully, although all sheep had been given iodinated
      cattle salt throughout the course of the history. Without reducing conditions
      sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of isolated
      thyroglobulin molecules of the ram and control sheep did not reveal different
      band patterns, but under reducing conditions different band patterns were evident
      for the respective animals: the ram's thyroglobulin displayed two main bands,
      those of healthy reference sheep only one. Both bands reacted equally with anti
      thyroglobulin antibodies, even with those produced by immunizing rabbits with
      single bands. The reduced single thyroglobulin band of healthy sheep corresponded
      to a truncated form of that molecule, whereas the additional main band of the ram
      was a more resistant, intact thyroglobulin subunit, as was shown by mass
      spectrometry. In conclusion, results of physico- and immunochemical
      investigations gave evidence of a modification of thyroglobulin with suspected
      different iodine binding properties in the ram. The latter finding may have
      clinical relevance in similar cases in other species, as it is an example of the
      impact that a minor change in a protein molecule may have on a complete metabolic
      pathway. Additionally, it could be shown, that in the ovine species the generally
      found single main band of thyroglobulin after reduction is a truncated form and
      not an intact subunit. This truncation seems to be induced in vitro by the
      reductive sample pretreatment prior to SDS-PAGE.

PMID- 15153080
TI  - Impact of inadequately controlled asthma: a need for targeted therapy?

PMID- 15153081
TI  - Use of exogenous erythropoietin in critically ill patients.
AB  - OBJECTIVE: Review the literature regarding the use of recombinant human
      erythropoietin (rHuEPO) to prevent red blood cell (RBC) transfusion in critically
      ill patients. DATA SOURCES: A computerized search of MEDLINE and EMBASE from 1966
      through June 2003 was conducted using the terms erythropoietin, anemia,
      hemoglobin, critical care, intensive care, surgery, trauma, burn, and
      transfusion. References of selected articles were reviewed. A manual search of
      critical care, surgery, trauma, burn, hematology, and pharmacy journals was
      conducted to identify relevant abstracts. RESULTS: Six randomized studies have
      evaluated exogenous administration of erythropoietin to prevent RBC transfusions
      in critically ill patients. Studies vary with respect to rHuEPO dosage regimens,
      dose of concurrently administered iron, patient characteristics, and transfusion
      thresholds. Administration of rHuEPO rapidly produces erythropoiesis to reduce
      the need for RBC transfusions. The largest study conducted to date used weekly
      rHuEPO administration and found a modest decrease in transfusion requirements
      although the time to first transfusion was delayed. Reduced intensive care unit
      (ICU) length of stay (LOS) was shown in only one study of surgical/trauma
      patients. Reduced LOS after ICU discharge was found in another study of severely
      ill patients (APACHE II score >22). Other clinical outcomes were not altered by
      rHuEPO use. No adverse events were associated with rHuEPO use although studies
      were not designed to evaluate safety. CONCLUSIONS: rHuEPO reduces the need for
      transfusions. A cost-effectiveness analysis of rHuEPO for this indication is
      needed. Defining an optimal dosage regimen, identifying patients most likely to
      respond to rHuEPO, and determining risk factors for ICU associated anaemia would
      provide information for appropriate rHuEPO utilization.

PMID- 15153082
TI  - Do statins slow down Alzheimer's disease? A review.
AB  - More than 4 million people suffer from Alzheimer's disease (AD) in the United
      States. The prevalence increases with age as the rate is 3% in those between 65
      and 74 years compared with 47% among those over 85 years of age. Some
      epidemiological studies have reported a decrease in the incidence of AD with the
      use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
      (statins). Other studies have shown statins to decrease Abeta peptides, but data
      regarding cognitive benefits is lacking in this patient population. There are
      also concerns that statins, which cross the blood-brain barrier may cause more
      side-effects, but more information is needed. Adverse events were either
      infrequently noted or not reported in most of the published studies, and at this
      time there is insufficient evidence to suggest the use of statins for cognitive
      improvements in patients with AD.

PMID- 15153083
TI  - Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors
      in post-operative pain control.
AB  - OBJECTIVE: To evaluate the relative analgesic efficacy and tolerability of single
      dose COX-2 inhibitors in post-operative pain management. METHOD: Systematic
      review of randomized controlled trials (RCTs). OUTCOME MEASURES: The area under
      the pain relief vs. time curve was used to evaluate the proportion of patient
      achieving at least 50% pain relief using validated equations. The proportions of
      patients experiencing any adverse event or specific adverse events were also
      examined. RESULTS: In all, 18 RCTs were included which contained 2783 patients.
      The results of the effects of single-dose analgesics on the basis of 50% of
      patients achieving pain relief over 6 h from dental pain models suggested that
      oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and
      the rate ratio (RR) was 2.11 (95% CI 1.6-2.75). Valdecoxib 40 mg was also more
      effective than oxycodone/paracetamol 10/1000 mg (RR 1.34; 95% CI 1.11-1.62).
      There was no significant differences between other oral COX-2 inhibitors and non
      selective non-steroidal anti-inflammatory drugs (NSAIDs), except that celecoxib
      200 mg was less effective than ibuprofen 400 mg (RR 0.66; 95% CI 0.48-0.90) and
      rofecoxib 50 mg (RR 0.65; 95% CI 0.49-0.87). The results from orthopaedic pain
      model showed no significant difference between rofecoxib 50 mg and naproxen
      sodium 550 mg (RR 1.04; 95% CI 0.73-1.49). The adverse effects of single-dose COX
      2 inhibitor used in short-term post-operative pain management were generally mild
      and less than non-selective NSAIDs, although there was no significant difference.
      CONCLUSIONS: The analgesic efficacy and tolerability of single-dose COX-2
      inhibitors were more effective than opioid-containing analgesics and similar to
      non-selective NSAIDs in post-operative pain management. Further studies are
      needed to examine the efficacy and tolerability of COX-2 inhibitors compared
      against active comparators over a longer duration to assess whether these short
      term effects are mirrored by longer-term outcomes and to determine their ultimate
      risk-benefit profile.

PMID- 15153084
TI  - Appropriate antibiotic utilization in seniors prior to hospitalization for
      community-acquired pneumonia is associated with decreased in-hospital mortality.
AB  - BACKGROUND: We analysed the association of mortality and prescription of
      antibiotics prior to hospitalization for community-acquired pneumonia. METHODS:
      We used administrative data (hospital abstracts, physician claims, prescriptions)
      for seniors (age 61 years and over) for Alberta, Canada from 1 April 1994 to 31
      March 1999. RESULTS: Hospitalization of 21 191 seniors occurred during the study
      period. In about 43% of hospitalizations (n = 9034), a physician was consulted
      prior to hospital admission. Antibiotics were dispensed to 31% of those with a
      prior physician visit and in about 72%, the antibiotic choice was deemed
      appropriate. The odds for mortality were significantly decreased in those with
      prior physician visits (OR = 0.87, P < 0.01), with any antibiotic prescription
      (OR = 0.66, P < 0.0001), and with an appropriate antibiotic (OR = 0.68, P =
      0.03). The choice of an appropriate antibiotic as opposed to an inappropriate
      antibiotic resulted in a 2.6% absolute and 38% relative mortality reduction.
      CONCLUSION: Choosing an appropriate outpatient antibiotic in accordance with
      published expert opinion guidelines compared with inappropriate antibiotic
      prescriptions decreased hospital mortality in patients subsequently hospitalized
      for community-acquired pneumonia.

PMID- 15153085
TI  - Herbal medicines: predictors of recommendation by physicians.
AB  - BACKGROUND: We hypothesized that as the use of herbal medicines increases in the
      general population, so do patients' requests to physicians for recommendations.
      However, why some physicians recommend herbal medicines while others do not is
      not well understood. OBJECTIVE: To identify factors, which predict recommendation
      of herbal medicines by physicians. DESIGN, LOCATION, SUBJECTS: Face-to-face
      interview using a structured questionnaire of 206 physicians working at the
      University of Malaya Medical Centre, Malaysia. RESULTS: About a third (206 of
      626) of the physicians in the Centre participated. Only nine of the 215
      approached refused to participate. Forty physicians (19%) recommended herbal
      medicines to patients. Logistic regression modelling identified personal use,
      general interest, interest in receiving training, race and higher level of
      medical training as significant predictors of physicians recommending herbal
      medicines. CONCLUSIONS: Physicians' personal attributes and training influence
      their likelihood of recommending herbal medicines.

PMID- 15153086
TI  - Population pharmacokinetic modeling of steady state clearance of carbamazepine
      and its epoxide metabolite from sparse routine clinical data.
AB  - OBJECTIVE: To develop a population pharmacokinetic model to evaluate the effects
      of variety of covariates on clearance of carbamazepine (CBZ) and its main
      metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese population. METHODS:
      Serum samples at steady trough state (n = 459) were collected prospectively from
      408 compliant outpatients during their routine clinical care. CBZ and CBZE
      concentrations were simultaneously determined by high performance liquid
      chromatography. Population clearance (CL) of CBZ and CBZE were estimated by non
      linear mixed effect modeling and NONMEM program with a one-compartment model of
      first-order absorption and elimination. RESULTS: Total body weight (TBW), dose
      and concomitant medication were all important determinants of CL of CBZ and CBZE.
      The final regression model for CBZ was: where VPA = 1 for patients comedicated
      with valproic acid and its dose greater than 18 mg/kg, otherwise VPA = 0; PHT = 1
      for patients comedicated with phenytoin, otherwise PHT = 0; PB = 1 for patients
      comedicated with phenytoin, otherwise PB = 0. The final regression CL model for
      the CBZE was: where VPA = 1 for patients comedicated with valproic acid,
      otherwise VPA = 0. CONCLUSION: The current models, which describe CL of CBZ and
      CBZE in terms of patient specific details, can be used as a reference to optimize
      CBZ therapy in Chinese epilepsy patients.

PMID- 15153087
TI  - A HRG-based costing model for estimating pharmacy costs associated with surgical
      procedures.
AB  - OBJECTIVE: The present study addresses pharmacy expenditure within a surgical
      directorate in a UK hospital. The aim of the study was to develop a health care
      resource group (HRG)-based costing model that can be used to forecast pharmacy
      expenditure based on surgical casemix. Such a model will be of benefit as an
      expenditure projection tool at a time when hospitals are developing accelerated
      operation programmes in an attempt to decrease hospital waiting times. METHOD:
      During the period February-April 2000, nursing staff recorded all pharmacy
      sourced items for each individual operation in the theatres used for general
      surgery, ENT surgery and gynaecological procedures; each operation was also
      classified according to its HRG. The associated costs of the items per HRG were
      identified and the average pharmaceutical cost per HRG calculated and included in
      the costing model. The model derived costs over the study period were compared
      with the actual pharmacy expenditure which was obtained from the pharmacy
      computer system. Finally HRG data for operations carried out in February 2002
      were costed using the model for validation purposes. RESULTS: The estimated
      pharmaceutical cost for surgery items for February-April 2000 was 121,235 UK
      pounds. This figure was 3.92% over the actual pharmaceutical expenditure as
      determined from computer records. The February 2002 casemix varied considerably
      from that of 2000. However, the model estimated pharmaceutical cost of surgery
      performed in February 2002 (38,054 UK pounds) was again very similar to the
      computer logged expenditure (1.09% under the actual expenditure for that period)
      indicating the robustness of the HRG-based costing approach.

PMID- 15153088
TI  - Testing the practical aspects of therapeutics by objective structured clinical
      examination.
AB  - Medical students need to have a sound theoretical knowledge of pharmacology and a
      training in the practical aspects of therapeutics in order to prescribe
      effectively, safely and rationally when they qualify. Students have traditionally
      sat written exams and the practical aspects have been largely ignored. At the
      University of Birmingham we set up an objective structured clinical examination
      (OSCE) style examination to test the practical aspects of therapeutics. Over the
      last 2 years, 434 students have been examined in this way to determine competency
      in various clinical skills including, for example prescription writing, the
      drawing up and giving of injections, setting up nebulizers, and patient
      counselling about drug effects. Over that time we found the therapeutics OSCE to
      be feasible and useful. It has demonstrated serious practical deficiencies that
      were not apparent from written examinations in some students' ability to
      prescribe and administer drugs. Since its introduction, performance in the OSCE
      has improved. Whether this will result in safer and more effective prescribing in
      the preregistration house officer year has not been formally evaluated but it
      appears that they approach this aspect of patient care with greater confidence
      than graduates from other schools.

PMID- 15153089
TI  - Influence of high-dose leucovorin and 5-fluorouracil chemotherapy regimen on P
      wave duration and dispersion.
AB  - BACKGROUND: Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known,
      atrial arrhythmia, as a potentially serious complication has not been studied in
      detail. The aim of this study was to determine the P max and Pd in the
      electrocardiograms (ECG) of patients receiving 5-FU treatment. METHODS: Twenty
      five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous
      infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac
      physical examinations, ECG and echocardiography were enrolled. P maximum (P max),
      P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration)
      were measured from the 12-lead ECG at the 0th and 48th hour of the first
      chemotherapy cycle. Echocardiography was also obtained in all patients at the
      same times. RESULTS: Clinical cardiotoxicity was observed in two patients. P max
      and Pd were both significantly longer after 5-FU treatment at the 48th hour (P <
      0.001). P min did not change (P > 0.05). CONCLUSION: Treatment with 5-FU based
      regimens may increase Pd and prolong the P max in cancer patients. These
      alterations may be predictive of patients at risk of atrial arrhythmias during 5
      FU treatment.

PMID- 15153090
TI  - Glucose self-monitoring in primary care: a survey of current practice.
AB  - BACKGROUND: The role of long-term glycaemic control in minimizing long-term
      complications of diabetes mellitus is evidence-based and national guidelines
      recommend a target glycosylated haemoglobin level of approximately 7%. Although
      the role of self-monitoring blood and urine glucose is less well defined, this
      activity consumes vast National Health Service (NHS) resources. AIMS: The aims of
      this study were to (i) determine the current practice of glucose self-monitoring
      in primary care, (ii) determine any changes to therapy made as a result and (iii)
      compare monitoring and frequency of monitoring in those patients using insulin
      with those patients taking oral hypoglycaemic agents. METHODS: Postal
      questionnaire to 311 patients using insulin or oral hypoglycaemic agents
      identified from three general practices. RESULTS: The response rate was 59.8%
      (186/311), with the majority of responding patients (n = 158, 87.3%) performing
      self-monitoring. The patients using insulin were more likely to be self
      monitoring than those taking oral therapy (chi(2), P < 0.001, d.f. = 1). The
      majority of patients who self-monitored and were using insulin (n = 45, 61.1%)
      altered the dose of insulin if a reading was beyond their target range. However,
      the majority of patients who self-monitored and were taking oral therapy (n = 48,
      68.6%) took no action at all. CONCLUSIONS: Blood glucose self-monitoring was
      common in those treated with insulin or oral hypoglycaemics, although those using
      insulin were more likely to self-monitor. Notably many patients, particularly
      those on oral therapy, took no action based on the results of self-monitoring.

PMID- 15153091
TI  - G-protein coupled receptors: SAR analyses of neurotransmitters and antagonists.
AB  - BACKGROUND: From the deductive point of view, neurotransmitter receptors can be
      divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic
      (alpha- and beta-), dopaminergic, serotoninergic (5-HT1 approximately 5-HT5), and
      histaminergic (H1 and H2). Selective agonists and antagonists of each receptor
      subtype can have specific useful therapeutic applications. For understanding the
      molecular mechanisms of action, an inductive method of analysis is useful.
      OBJECTIVE: The aim of the present study is to examine the structure-activity
      relationships of agents acting on G-protein coupled receptors. METHOD:
      Representative sets of G-PCR agonists and antagonists were identified from the
      literature and Medline [P.M. Walsh (2003) Physicians' Desk Reference; M.J. O'Neil
      (2001) The Merck Index]. The molecular weight (MW), calculated logarithm of
      octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole
      moment (DM), E(lumo) (the energy of the lowest unoccupied molecular orbital, a
      measure of the electron affinity of a molecule and its reactivity as an
      electrophile), E(homo) (the energy of the highest occupied molecular orbital,
      related to the ionization potential of a molecule, and its reactivity as a
      nucleophile), and the total number of hydrogen bonds (H(b)) (donors and
      receptors), were chosen as molecular descriptors for SAR analyses. RESULTS: The
      data suggest that not only do neurotransmitters share common structural features
      but their receptors belong to the same ensemble of G-protein coupled receptor
      with seven to eight transmembrane domains with their resultant dipoles in an
      antiparallel configuration. Moreover, the analysis indicates that the receptor
      exists in a dynamic equilibrium between the closed state and the open state. The
      energy needed to open the closed state is provided by the hydrolysis of GTP. A
      composite 3-D parameter frame setting of all the neurotransmitter agonists and
      antagonists are presented using MW, Hb and mu as independent variables.
      CONCLUSION: It appears that all neurotransmitters examined in this study operate
      by a similar mechanism with the G-protein coupled receptors.

PMID- 15153093
TI  - Role of extracellular signal regulated kinases 1 and 2 in neuronal survival.
AB  - Extracellular signal regulated kinases 1 and 2 (ERK1/2) regulate cellular
      responses to a variety of extracellular stimuli. In the nervous system, ERK1/2 is
      critical for neuronal differentiation, plasticity and may also modulate neuronal
      survival. In this minireview, we present evidence that supports prosurvival
      activity of ERK1/2 in neurons. Several reports suggest that ERK1/2 mediates
      neuroprotective activity of extracellular factors, including neurotrophins. In
      addition, ERK1/2 is activated by neuronal injury. In damaged cells, ERK1/2
      activation may act as a defensive mechanism that helps to compensate for the
      deleterious effects of a damaging insult. The emerging mechanisms of ERK1/2
      mediated neuroprotection may involve transcriptional regulation and/or direct
      inhibition of cell death machinery.

PMID- 15153094
TI  - Role of extracellular signal regulated kinase 5 in neuronal survival.
AB  - The newest member of the mitogen activated protein (MAP) kinase family of
      proteins, extracellular signal regulated kinase 5 (ERK5; also known as big
      mitogen activated kinase 1 or BMK1) is widely expressed in many tissues including
      the brain. Although growth factor activation of ERK5 in non-neuronal cells has
      been shown to contribute to cell proliferation, differentiation and
      transformation, until recently no information was available on the role of ERK5
      in neuronal survival. Recent data suggests that ERK5 is activated by neurotrophic
      factors in primary neuronal cells and plays an important role in neurotrophin
      mediated neuronal survival. These data also suggest that the mechanism of ERK5
      mediated survival involves transcriptional regulation.

PMID- 15153096
TI  - Structure and function of plant aspartic proteinases.
AB  - Aspartic proteinases of the A1 family are widely distributed among plant species
      and have been purified from a variety of tissues. They are most active at acidic
      pH, are specifically inhibited by pepstatin A and contain two aspartic residues
      indispensible for catalytic activity. The three-dimensional structure of two
      plant aspartic proteinases has been determined, sharing significant structural
      similarity with other known structures of mammalian aspartic proteinases. With a
      few exceptions, the majority of plant aspartic proteinases identified so far are
      synthesized with a prepro-domain and subsequently converted to mature two-chain
      enzymes. A characteristic feature of the majority of plant aspartic proteinase
      precursors is the presence of an extra protein domain of about 100 amino acids
      known as the plant-specific insert, which is highly similar both in sequence and
      structure to saposin-like proteins. This insert is usually removed during
      processing and is absent from the mature form of the enzyme. Its functions are
      still unclear but a role in the vacuolar targeting of the precursors has been
      proposed. The biological role of plant aspartic proteinases is also not
      completely established. Nevertheless, their involvement in protein processing or
      degradation under different conditions and in different stages of plant
      development suggests some functional specialization. Based on the recent findings
      on the diversity of A1 family members in Arabidopsis thaliana, new questions
      concerning novel structure-function relationships among plant aspartic
      proteinases are now starting to be addressed.

PMID- 15153095
TI  - Oxidative neuronal injury. The dark side of ERK1/2.
AB  - The extracellular signal regulated protein kinases (ERK1/2) are essential for
      normal development and functional plasticity of the central nervous system.
      However, a growing number of recent studies in models of cerebral ischemia, brain
      trauma and neurodegenerative diseases implicate a detrimental role for ERK1/2
      signaling during oxidative neuronal injury. Neurons undergoing oxidative stress
      related injuries typically display a biphasic or sustained pattern of ERK1/2
      activation. A variety of potential targets of reactive oxygen species and
      reactive nitrogen species could contribute to ERK1/2 activation. These include
      cell surface receptors, G proteins, upstream kinases, protein phosphatases and
      proteasome components, each of which could be direct or indirect targets of
      reactive oxygen or nitrogen species, thereby modulating the duration and
      magnitude of ERK1/2 activation. Neuronal oxidative stress also appears to
      influence the subcellular trafficking and/or localization of activated ERK1/2.
      Differences in compartmentalization of phosphorylated ERK1/2 have been observed
      in diseased or injured human neurons and in their respective animal and cell
      culture model systems. We propose that differential accessibility of ERK1/2 to
      downstream targets, which is dictated by the persistent activation of ERK1/2
      within distinct subcellular compartments, underlies the neurotoxic responses that
      are driven by this kinase.

PMID- 15153097
TI  - Structure and potential C-terminal dimerization of a recombinant mutant of
      surfactant-associated protein C in chloroform/methanol.
AB  - The solution structure of a recombinant mutant [rSP-C (FFI)] of the human
      surfactant-associated protein C (hSP-C) in a mixture of chloroform and methanol
      was determined by high-resolution NMR spectroscopy. rSP-C (FFI) contains a helix
      from Phe5 to the C-terminal Leu34 and is thus longer by two residues than the
      helix of porcine SP-C (pSP-C), which is reported to start at Val7 in the same
      solvent. Two sets of resonances at the C-terminus of the peptide were observed,
      which are explained by low-order oligomerization, probably dimerization of rSP-C
      (FFI) in its alpha-helical form. The dimerization may be induced by hydrogen
      bonding of the C-terminal carboxylic groups or by the strictly conserved C
      terminal heptapeptide segment with a motif similar to the GxxxG dimerization
      motif of glycophorin A. Dimerization at the heptapeptide segment would be
      consistent with findings based on electrospray ionization MS data, chemical cross
      linking studies, and CNBr cleavage data.

PMID- 15153098
TI  - Structural model for an AxxxG-mediated dimer of surfactant-associated protein C.
AB  - The pulmonary surfactant prevents alveolar collapse and is required for normal
      pulmonary function. One of the important components of the surfactant besides
      phospholipids is surfactant-associated protein C (SP-C). SP-C shows complex
      oligomerization behavior and a transition to beta-amyloid-like fibril structures,
      which are not yet fully understood. Besides this nonspecific oligomerization, MS
      and chemical cross-linking data combined with CD spectra provide evidence of a
      specific, mainly alpha-helical, dimer at low to neutral pH. Furthermore,
      resistance to CNBr cleavage and dual NMR resonances of porcine and human
      recombinant SP-C with Met32 replaced by isoleucine point to a dimerization site
      located at the C-terminus of the hydrophobic alpha-helix of SP-C, where a
      strictly conserved heptapeptide sequence is found. Computational docking of two
      SP-C helices, described here, reveals a dimer with a helix-helix interface that
      strikingly resembles that of glycophorin A and is mediated by an AxxxG motif
      similar to the experimentally determined GxxxG pattern of glycophorin A. It is
      highly likely that mature SP-C adopts such a dimeric structure in the lamellar
      bilayer systems found in the surfactant. Dimerization has been shown in previous
      studies to have a role in sorting and trafficking of SP-C and may also be
      important to the surfactant function of this protein.

PMID- 15153099
TI  - Bacterial IscU is a well folded and functional single domain protein.
AB  - Iron-sulfur clusters are widely represented in most organisms, but the mechanism
      of their formation is not fully understood. Of the two main proteins involved in
      cluster formation, NifS/IscS and NifU/IscU, only the former has been well studied
      from a structural point of view. Here we report an extensive structural
      characterization of Escherichia coli IscU. We show by a variety of physico
      chemical techniques that E. coli IscU construct can be expressed to high purity
      as a monomeric protein, characterized by an alphabeta fold with high alpha-helix
      content. The high melting temperature and the reversibility of the thermal
      unfolding curve (as measured by CD spectroscopy) hint at a well ordered stable
      fold. The excellent dispersion of cross peaks in the (1)H-(15)N correlation
      spectrum is consistent with these observations. Monomeric E. coli IscU is able to
      provide a scaffold for Iron-sulfur cluster assembly, but has no direct
      interaction with either Fe(II) or Fe(III) ions, suggesting the need of further
      partners to achieve a stable interaction.

PMID- 15153100
TI  - Angiotensin-converting enzyme inhibition studies by natural leech inhibitors by
      capillary electrophoresis and competition assay.
AB  - A protocol to follow the processing of angiotensin I into angiotensin II by
      rabbit angiotensin-converting enzyme (ACE) and its inhibition by a novel natural
      antagonist, the leech osmoregulator factor (LORF) using capillary zonal
      electrophoresis is described. The experiment was carried out using the Beckman
      PACE system and steps were taken to determine (a) the migration profiles of
      angiotensin and its yielded peptides, (b) the minimal amount of angiotensin II
      detected, (c) the use of different electrolytes and (d) the concentration of
      inhibitor. We demonstrated that LORF (IPEPYVWD), a neuropeptide previously found
      in leech brain, is able to inhibit rabbit ACE with an IC(50) of 19.8 micro m.
      Interestingly, its cleavage product, IPEP exhibits an IC(50) of 11.5 micro m. A
      competition assay using p-benzoylglycylglycylglycine and insect ACE established
      that LORF and IPEP fragments are natural inhibitors for invertebrate ACE. Fifty
      four percent of insect ACE activity is inhibited with 50 micro m IPEP and 35%
      inhibition with LORF (25 mm). Extending the peptide at both N- and C-terminus
      (GWEIPEPYVWDES) and the cleavage of IPEP in IP abolished the inhibitory activity
      of both peptides. Immunocytochemical data obtained with antisera raised against
      LORF and leech ACE showed a colocalization between the enzyme and its inhibitor
      in the same neurons. These results showed that capillary zonal electrophoresis is
      a useful technique for following enzymatic processes with small amounts of
      products and constitutes the first evidence of a natural ACE inhibitor in
      invertebrates.

PMID- 15153101
TI  - Identifying determinants of NADPH specificity in Baeyer-Villiger monooxygenases.
AB  - The Baeyer-Villiger monooxygenase (BVMO), 4-hydroxyacetophenone monooxygenase
      (HAPMO), uses NADPH and O(2) to oxidize a variety of aromatic ketones and
      sulfides. The FAD-containing enzyme has a 700-fold preference for NADPH over
      NADH. Sequence alignment with other BVMOs, which are all known to be selective
      for NADPH, revealed three conserved basic residues, which could account for the
      observed coenzyme specificity. The corresponding residues in HAPMO (Arg339,
      Lys439 and Arg440) were mutated and the properties of the purified mutant enzymes
      were studied. For Arg440 no involvement in coenzyme recognition could be shown as
      mutant R440A was totally inactive. Although this mutant could still be fully
      reduced by NADPH, no oxygenation occurred, indicating that this residue is
      crucial for completing the catalytic cycle of HAPMO. Characterization of several
      Arg339 and Lys439 mutants revealed that these residues are indeed both involved
      in coenzyme recognition. Mutant R339A showed a largely decreased affinity for
      NADPH, as judged from kinetic analysis and binding experiments. Replacing Arg339
      also resulted in a decreased catalytic efficiency with NADH. Mutant K439A
      displayed a 100-fold decrease in catalytic efficiency with NADPH, mainly caused
      by an increased K(m). However, the efficiency with NADH increased fourfold.
      Saturation mutagenesis at position 439 showed that the presence of an asparagine
      or a phenylalanine improves the catalytic efficiency with NADH by a factor of 6
      to 7. All Lys439 mutants displayed a lower affinity for AADP(+), confirming a
      role of the lysine in recognizing the 2'-phosphate of NADPH. The results obtained
      could be extrapolated to the sequence-related cyclohexanone monooxygenase.
      Replacing Lys326 in this BVMO, which is analogous to Lys439 in HAPMO, again
      changed the coenzyme specificity towards NADH. These results indicate that the
      strict NADPH dependency of this class of monooxygenases is based upon recognition
      of the coenzyme by several basic residues.

PMID- 15153102
TI  - A Kazal prolyl endopeptidase inhibitor isolated from the skin of Phyllomedusa
      sauvagii.
AB  - Searching for bioactive peptides, we analyzed acidic extracts of Phyllomedusa
      sauvagii skin and found two new proteins, PSKP-1 and PSKP-2, of 6.7 and 6.6 kDa,
      respectively, which, by sequence homology, belong to the Kazal family of serine
      protease inhibitors. PSKP-1 and PSKP-2 exhibit the unprecedented feature of
      having proline at P(1) and P(2) positions. A gene encoding PSKP-1 was synthesized
      and expressed in Escherichia coli. Recombinant PSKP-1 was purified from inclusion
      bodies, oxidatively refolded to the native state, and characterized by chemical,
      hydrodynamic and optical studies. PSKP-1 shows inhibitory activity against a
      serum prolyl endopeptidase, but is unable to inhibit trypsin, chymotrypsin, V8
      protease, or proteinase K. In addition, PSKP-1 can be rendered active against
      trypsin by active-site site-specific mutagenesis, has bactericidal activity, and
      induces agglutination of red cells at micromolar concentrations. PSKP-1 might
      protect P. sauvagii teguments from microbial invasion, by acting as an inhibitor
      of an as-yet unidentified prolyl endopeptidase or directly as a microbicidal
      compound.

PMID- 15153103
TI  - Poneratoxin, a neurotoxin from ant venom. Structure and expression in insect
      cells and construction of a bio-insecticide.
AB  - Poneratoxin is a small neuropeptide found in the venom of the ant Paraponera
      clavata. It is stored in the venom reservoir as an inactive 25-residue peptide.
      Here we describe both chemically synthesized poneratoxin and poneratoxin obtained
      by expression in insect cells. When expressed in insect cells, poneratoxin was
      observed attached to cell membranes. Both synthetic and recombinant ponerotoxins
      were soluble below pH 4.5. The structure of synthetic poneratoxin was
      characterized by circular dichroism and solved by nuclear magnetic resonance. In
      an environment imitating a lipid bilayer, at pH within the range of insect
      hemolymph, synthetic poneratoxin has a V shape, with two alpha-helices connected
      by a beta-turn. Insect larvae were paralyzed by injection of either of the
      purified toxins, with the recombinant one acting faster. The recombinant toxin
      producing baculovirus reduced the average survival time of the insect host by 25
      h compared with unmodified virus. Mass spectrometry analysis showed that the
      recombinant toxin has an N-terminal 21-residue extension, possibly improving its
      stability and/or stabilizing the membrane-bound state. The potential use of
      poneratoxin for the construction of biological insecticide is discussed.

PMID- 15153105
TI  - Tet repressor residues indirectly recognizing anhydrotetracycline.
AB  - Two tetracycline repressor (TetR) sequence variants sharing 63% identical amino
      acids were investigated in terms of their recognition specificity for
      tetracycline and anhydrotetracycline. Thermodynamic complex stabilities
      determined by urea-dependent unfolding reveal that tetracycline stabilizes both
      variants to a similar extent but that anhydrotetracycline discriminates between
      them significantly. Isofunctional TetR hybrid proteins of these sequence variants
      were constructed and their denaturation profiles identified residues 57 and 61 as
      the complex stability determinant. Association kinetics reveal different
      recognition of these TetR variants by anhydrotetracycline, but the binding
      constants indicate similar stabilization. The identified residues connect to an
      internal water network, which suggests that the discrepancy in the observed
      thermodynamics may be caused by an entropy effect. Exchange of these interacting
      residues between the two TetR variants appears to influence the flexibility of
      this water organization, demonstrating the importance of buried, structural water
      molecules for ligand recognition and protein function. Therefore, this structural
      module seems to be a key requisite for the plasticity of the multiple ligand
      binding protein TetR.

PMID- 15153104
TI  - Fibroblast growth-stimulating activity of S100A9 (MRP-14).
AB  - Fibroblasts play a critical role in chronic inflammation and wound healing. In
      this study, a fibroblast growth-stimulating factor was purified from the exudate
      of carrageenan-induced inflammation in rats. The purified protein was a disulfide
      linked homodimer. Amino acid sequence analysis of the peptides generated by
      cleavage with cyanogen bromide and proteinase V8 resulted in identification of
      the protein as S100A9. Recombinant S100A9 as well as its disulfide-linked
      homodimer stimulated the proliferation of fibroblasts at a similar concentration
      of the purified protein. The concentration of S100A9 in the exudate was
      determined by immunoblot analysis. The total protein concentration in the exudate
      reached a maximum 4 days after carrageenan injection and then slightly decreased,
      whereas the concentration of S100A9 reached a maximum at day 3 and then decreased
      rapidly. These studies show that S100A9 is present at a high concentration in the
      exudate of carrageenan-induced inflammation in rats, and that S100A9 stimulates
      proliferation of fibroblasts, suggesting that it plays a role in chronic
      inflammation.

PMID- 15153106
TI  - Survey of the Botrytis cinerea chitin synthase multigenic family through the
      analysis of six euascomycetes genomes.
AB  - We describe a strategy for systematic amplification of chitin synthase genes
      (chs) in the filamentous ascomycetes plant-pathogen Botrytis cinerea using PCR
      with multiple degenerate primers designed on specific and conserved sequence
      motifs. Eight distinct chs genes were isolated, named Bcchs I, II, IIIa, IIIb,
      IV, V, VI and VII. They probably constitute the entire chs multigenic family of
      this fungus, as revealed by careful analysis of six euascomycetes genomes. Bcchs
      I, IIIa, IIIb, IV and VI genes were subjected to DNA walking and their deduced
      amino acid sequences were compared by hydrophobic cluster analysis (HCA) to
      localize putative residues critical for CHS activity. HCA also enabled us to
      highlight three different transmembrane topologies of the CHS membranous
      isoenzymes. We found that the N-terminal region of the BcCHSI isoenzyme, and its
      orthologues in other euascomycetes, probably contain folded peptide motifs with
      conserved tyrosine residues. Their putative role is discussed. The BcCHSVII
      isoenzyme appeared to belong to a new class of CHS orthologues that was
      demonstrated by phylogenetic study to branch apart from division 1 and 2 of CHS.

PMID- 15153107
TI  - The conformational stability of the Streptomyces coelicolor histidine
      phosphocarrier protein. Characterization of cold denaturation and urea-protein
      interactions.
AB  - Thermodynamic parameters describing the conformational stability of the histidine
      containing phosphocarrier protein from Streptomyces coelicolor, scHPr, have been
      determined by steady-state fluorescence measurements of isothermal urea
      denaturations, differential scanning calorimetry at different guanidinium
      hydrochloride concentrations and, independently, by far-UV circular dichroism
      measurements of isothermal urea-denaturations, and thermal denaturations at fixed
      urea concentrations. The equilibrium unfolding transitions are described
      adequately by the two-state model and they validate the linear free-energy
      extrapolation model, over the large temperature range explored, and the urea
      concentrations used. At moderate urea concentrations (from 2 to 3 m), scHPr
      undergoes both high- and low-temperature unfolding. The free-energy stability
      curves have been obtained for the whole temperature range and values of the
      thermodynamic parameters governing the heat- and cold-denaturation processes have
      been obtained. Cold-denaturation of the protein is the result of the combination
      of an unusually high heat capacity change (1.4 +/- 0.3 kcal.mol(-1).K(-1), at 0 m
      urea, being the average of the fluorescence, circular dichroism and differential
      scanning calorimetry measurements) and a fairly low enthalpy change upon
      unfolding at the midpoint temperature of heat-denaturation (59 +/- 4 kcal.mol(
      1), the average of the fluorescence, circular dichroism and differential scanning
      calorimetry measurements). The changes in enthalpy (m(DeltaH(i) )), entropy
      (m(DeltaS(i) )) and heat capacity (m(DeltaC(pi) )), which occur upon preferential
      urea binding to the unfolded state vs. the folded state of the protein, have also
      been determined. The m(DeltaH(i) ) and the m(DeltaS(i) ) are negative at low
      temperatures, but as the temperature is increased, m(DeltaH(i) ) makes a less
      favourable contribution than m(DeltaS(i) ) to the change in free energy upon urea
      binding. The m(DeltaC(pi) ) is larger than those observed for other proteins;
      however, its contribution to the global heat capacity change upon unfolding is
      small.

PMID- 15153108
TI  - ATPase activity of magnesium chelatase subunit I is required to maintain subunit
      D in vivo.
AB  - During biosynthesis of chlorophyll, Mg(2+) is inserted into protoporphyrin IX by
      magnesium chelatase. This enzyme consists of three different subunits of
      approximately 40, 70 and 140 kDa. Seven barley mutants deficient in the 40 kDa
      magnesium chelatase subunit were analysed and it was found that this subunit is
      essential for the maintenance of the 70 kDa subunit, but not the 140 kDa subunit.
      The 40 kDa subunit has been shown to belong to the family of proteins called
      "ATPases associated with various cellular activities", known to form ring-shaped
      oligomeric complexes working as molecular chaperones. Three of the seven barley
      mutants are semidominant mis-sense mutations leading to changes of conserved
      amino acid residues in the 40 kDa protein. Using the Rhodobacter capsulatus 40
      and 70 kDa magnesium chelatase subunits we have analysed the effect of these
      mutations. Although having no ATPase activity, the deficient 40 kDa subunit could
      still associate with the 70 kDa protein. The binding was dependent on Mg(2+) and
      ATP or ADP. Our study demonstrates that the 40 kDa subunit functions as a
      chaperon that is essential for the survival of the 70 kDa subunit in vivo. We
      conclude that the ATPase activity of the 40 kDa subunit is essential for this
      function and that binding between the two subunits is not sufficient to maintain
      the 70 kDa subunit in the cell. The ATPase deficient 40 kDa proteins fail to
      participate in chelation in a step after the association of the 40 and 70 kDa
      subunits. This step presumably involves a conformational change of the complex in
      response to ATP hydrolysis.

PMID- 15153109
TI  - Characterization of mammalian eIF4E-family members.
AB  - The translational factor eukaryotic initiation factor 4E (eIF4E) is a central
      component in the initiation and regulation of translation in eukaryotic cells.
      Through its interaction with the 5' cap structure of mRNA, eIF4E functions to
      recruit mRNAs to the ribosome. The accumulation of expressed sequence tag
      sequences has allowed the identification of three different eIF4E-family members
      in mammals termed eIF4E-1, eIF4E-2 (4EHP, 4E-LP) and eIF4E-3, which differ in
      their structural signatures, functional characteristics and expression patterns.
      Unlike eIF4E-1, which is found in all eukaryotes, orthologues for eIF4E-2 appear
      to be restricted to metazoans, while those for eIF4E-3 have been found only in
      chordates. Like prototypical eIF4E-1, eIF4E-2 was found to be ubiquitously
      expressed, with the highest levels in the testis. Expression of eIF4E-3 was
      detected only in heart, skeletal muscle, lung and spleen. Similarly to eIF4E-1,
      both eIF4E-2 and eIF4E-3 can bind to the mRNA cap-structure. However, in contrast
      to eIF4E-1 which interacts with both the scaffold protein, eIF4G and the
      translational repressor proteins, the eIF4E-binding proteins (4E-BPs), eIF4E-2
      and eIF4E-3 each possesses a range of partial activities. eIF4E-2 does not
      interact with eIF4G, but does interact with 4E-BPs. Conversely, eIF4E-3 interacts
      with eIF4G, but not with 4E-BPs. Neither eIF4E-2 nor eIF4E-3 is able to rescue
      the lethality of eIF4E gene deletion in yeast. It is hypothesized that each eIF4E
      family member fills a specialized niche in the recruitment of mRNAs by the
      ribosome through differences in their abilities to bind cap and/or to interact
      with eIF4G and the 4E-BPs.

PMID- 15153110
TI  - Glycosphingolipids in Plasmodium falciparum. Presence of an active
      glucosylceramide synthase.
AB  - Malaria remains a major health problem especially in tropical and subtropical
      regions of the world, and therefore developing new antimalarial drugs constitutes
      an urgent challenge. Lipid metabolism has been attracting a lot of attention as
      an application for malarial chemotherapeutic purposes in recent years. However,
      little is known about glycosphingolipid biosynthesis in Plasmodium falciparum. In
      this report we describe for the first time the presence of an active
      glucosylceramide synthase in the intraerythrocytic stages of the parasite. Two
      different experiments, using UDP-[(14)C]glucose as donor with ceramides as
      acceptors, or UDP-glucose as donor and fluorescent ceramides as acceptors, were
      performed. In both cases, we found that the parasitic enzyme was able to
      glycosylate only dihydroceramide. The enzyme activity could be inhibited in vitro
      with low concentrations of d,l-threo-phenyl-2-palmitoylamino-3-morpholino-1
      propanol (PPMP). In addition, de novo biosynthesis of glycosphingolipids was
      shown by metabolic incorporation of [(14)C]palmitic acid and [(14)C]glucose in
      the three intraerythrocytic stages of the parasite. The structure of the
      ceramide, monohexosylceramide, trihexosylceramide and tetrahexosylceramide
      fractions was analysed by UV-MALDI-TOF mass spectrometry. When PPMP was added to
      parasite cultures, a correlation between arrest of parasite growth and inhibition
      of glycosphingolipid biosynthesis was observed. The particular substrate
      specificity of the malarial glucosylceramide synthase must be added to the
      already known unique and amazing features of P. falciparum lipid metabolism;
      therefore this enzyme might represent a new attractive target for malarial
      chemotherapy.

PMID- 15153111
TI  - Covalent activation of heart AMP-activated protein kinase in response to
      physiological concentrations of long-chain fatty acids.
AB  - Rat hearts were perfused for 1 h with 5 mm glucose with or without palmitate or
      oleate at concentrations characteristic of the fasting state. The inclusion of
      fatty acids resulted in increased activities of the alpha-1 or the alpha-2
      isoforms of AMP-activated protein kinase (AMPK), increased phosphorylation of
      acetyl-CoA carboxylase and a decrease in the tissue content of malonyl-CoA.
      Activation of AMPK was not accompanied by any changes in the tissue contents of
      ATP, ADP, AMP, phosphocreatine or creatine. Palmitate increased phosphorylation
      of Thr172 within AMPK alpha-subunits and the activation by palmitate of both AMPK
      isoforms was abolished by protein phosphatase 2C leading to the conclusion that
      exposure to fatty acid caused activation of an AMPK kinase or inhibition of an
      AMPK phosphatase. In vivo, 24 h of starvation also increased heart AMPK activity
      and Thr172 phosphorylation of AMPK alpha-subunits. Perfusion with insulin
      decreased both alpha-1 and alpha-2 AMPK activities and increased malonyl-CoA
      content. Palmitate prevented both of these effects. Perfusion with epinephrine
      decreased malonyl-CoA content without an effect on AMPK activity but prevented
      the activation of AMPK by palmitate. The concept is discussed that activation of
      AMPK by an unknown fatty acid-driven signalling process provides a mechanism for
      a 'feed-forward' activation of fatty acid oxidation.

PMID- 15153112
TI  - Subunit composition of the glycyl radical enzyme p-hydroxyphenylacetate
      decarboxylase. A small subunit, HpdC, is essential for catalytic activity.
AB  - p-Hydroxyphenylacetate decarboxylase from Clostridium difficile catalyses the
      decarboxylation of p-hydroxyphenylacetate to yield the cytotoxic compound p
      cresol. The three genes encoding two subunits of the glycyl-radical enzyme and
      the activating enzyme have been cloned and expressed in Escherichia coli. The
      recombinant enzymes were used to reconstitute a catalytically functional system
      in vitro. In contrast with the decarboxylase purified from C. difficile, which
      was an almost inactive homo-dimeric protein (beta(2)), the recombinant enzyme was
      a hetero-octameric (beta(4)gamma(4)), catalytically competent complex, which was
      activated using endogenous activating enzyme from C. difficile or recombinant
      activating enzyme to a specific activity of 7 U.mg(-1). Preliminary results
      suggest that phosphorylation of the small subunit is responsible for the change
      of the oligomeric state. These data point to an essential function of the small
      subunit of the decarboxylase and may indicate unique regulatory properties of the
      system.

PMID- 15153113
TI  - Interaction of sweet proteins with their receptor. A conformational study of
      peptides corresponding to loops of brazzein, monellin and thaumatin.
AB  - The mechanism of interaction of sweet proteins with the T1R2-T1R3 sweet taste
      receptor has not yet been elucidated. Low molecular mass sweeteners and sweet
      proteins interact with the same receptor, the human T1R2-T1R3 receptor. The
      presence on the surface of the proteins of "sweet fingers", i.e. protruding
      features with chemical groups similar to those of low molecular mass sweeteners
      that can probe the active site of the receptor, would be consistent with a single
      mechanism for the two classes of compounds. We have synthesized three cyclic
      peptides corresponding to the best potential "sweet fingers" of brazzein,
      monellin and thaumatin, the sweet proteins whose structures are well
      characterized. NMR data show that all three peptides have a clear tendency, in
      aqueous solution, to assume hairpin conformations consistent with the
      conformation of the same sequences in the parent proteins. The peptide
      corresponding to the only possible loop of brazzein, c[CFYDEKRNLQC(37-47)],
      exists in solution in a well ordered hairpin conformation very similar to that of
      the same sequence in the parent protein. However, none of the peptides has a
      sweet taste. This finding strongly suggests that sweet proteins recognize a
      binding site different from the one that binds small molecular mass sweeteners.
      The data of the present work support an alternative mechanism of interaction, the
      "wedge model", recently proposed for sweet proteins [Temussi, P. A. (2002) FEBS
      Lett.526, 1-3.].

PMID- 15153114
TI  - Usefulness of microchip electrophoresis for reliable analyses of nonstandard DNA
      samples and subsequent on-chip enzymatic digestion.
AB  - The Hitachi SV1100 utilizes capillary electrophoresis on a microchip that is
      capable of rapidly sizing DNA fragments. Reproducibility of electrophoresis in
      different channels was shown by comparing the migration times of the internal
      controls, DNA fragments of 100 and 800 bp. The range of DNA sizing for this
      microchip is between 100 and 800 bp, and accuracy in sizing of a 322 bp DNA
      fragment of a pUC118 PvuII digest was observed, independent of DNA concentration.
      Although relatively good quantification of this fragment was observed with a DNA
      concentration of 1.83 ng.microL(-1), error increased in a dose-dependent manner.
      Furthermore, the feasibility of sequential analysis with this microchip was shown
      by the reproducibility of successive electrophoreses of the internal control in
      one channel. When the pUC118 PvuII digest was treated with endonuclease KpnI on
      the microchip for 10 min, sequential analysis showed that the 322 bp fragment
      completely disappeared and two peaks corresponding to the 130 and 192 bp
      fragments appeared. This analysis was performed within 4 min, and the peaks were
      estimated as 127 and 183 bp, respectively. These results indicate the potential
      of on-microchip endonuclease treatment of plasmid DNA with sequential analysis,
      offering high resolution in a short time.

PMID- 15153115
TI  - Effect of valine 106 on structure-function relation of cytosolic human thymidine
      kinase. Kinetic properties and oligomerization pattern of nine substitution
      mutants of V106.
AB  - Information on the regulation and structure-function relation of enzymes involved
      in DNA precursor synthesis is pivotal, as defects in several of these enzymes
      have been found to cause depletion or deletion of mitochondrial DNA resulting in
      severe diseases. Here, the effect of amino acid 106 on the enzymatic properties
      of the cell-cycle-regulated human cytosolic thymidine kinase 1 (TK1) is
      investigated. On the basis of the previously observed profound differences
      between recombinant TK1 with Val106 (V106WT) and Met106 (V106M) in catalytic
      activity and oligomerization pattern, we designed and characterized nine mutants
      of amino acid 106 differing in size, conformation and polarity. According to
      their oligomerization pattern and thymidine kinetics, the TK1 mutants can be
      divided into two groups. Group I (V106A, V106I and V106T) behaves like V106WT, in
      that pre-assay exposure to ATP induces reversible transition from a dimer with
      low catalytic activity to a tetramer with high catalytic activity. Group II
      (V106G, V106H, V106K, V106L and V106Q) behaves like V106M in that they are
      permanently high activity tetramers, irrespective of ATP exposure. We conclude
      that size and conformation of amino acid 106 are more important than polarity for
      the catalytic activity and oligomerization of TK1. The role of amino acid 106 and
      the sequence surrounding it for dimer-tetramer transition was confirmed by
      cloning the putative interface fragment of human TK1 and investigating its
      oligomerization pattern.

PMID- 15153116
TI  - K8 and K12 are biotinylated in human histone H4.
AB  - Folding of DNA into chromatin is mediated by binding to histones such as H4;
      association of DNA with histones is regulated by covalent histone modifications,
      e.g. acetylation, methylation, and biotinylation. We sought to identify amino
      acid residues that are biotinylated in histone H4, and to determine whether
      acetylation and methylation of histones affect biotinylation. Synthetic peptides
      spanning fragments of human histone H4 were biotinylated enzymatically using
      biotinidase. Peptide-bound biotin was probed with streptavidin-peroxidase.
      Peptides based on the N-terminal sequence of histone H4 were effectively
      recognized by biotinidase as substrates for biotinylation; in contrast, peptides
      based on the C-terminal sequences were not biotinylated. Substitution of K8 or
      K12 with alanine or arginine decreased biotinylation, suggesting that these
      lysines are targets for biotinylation; K8 and K12 are also known targets for
      acetylation. Chemical acetylation or methylation of a given lysine decreased
      subsequent enzymatic biotinylation of neighboring lysines, consistent with cross
      talk among histone modifications. Substitution of a given lysine (positive
      charge) with glutamate (negative charge) abolished biotinylation of neighboring
      lysines, providing evidence that the net charge of histones has a role in
      biotinylation. An antibody was generated that specifically recognized histone H4
      biotinylated at K12. This antibody was used to detect biotinylated histone H4 in
      nuclear extracts from human cells. These studies suggest that K8 and K12 in
      histone H4 are targets for biotinylation, that acetylation and biotinylation
      compete for the same binding sites, and that acetylation and methylation of
      histones affect biotinylation of neighboring lysines.

PMID- 15153117
TI  - Modeling the Qo site of crop pathogens in Saccharomyces cerevisiae cytochrome b.
AB  - Saccharomyces cerevisiae has been used as a model system to characterize the
      effect of cytochrome b mutations found in fungal and oomycete plant pathogens
      resistant to Q(o) inhibitors (QoIs), including the strobilurins, now widely
      employed in agriculture to control such diseases. Specific residues in the Q(o)
      site of yeast cytochrome b were modified to obtain four new forms mimicking the
      Q(o) binding site of Erysiphe graminis, Venturia inaequalis, Sphaerotheca
      fuliginea and Phytophthora megasperma. These modified versions of cytochrome b
      were then used to study the impact of the introduction of the G143A mutation on
      bc(1) complex activity. In addition, the effects of two other mutations F129L and
      L275F, which also confer levels of QoI insensitivity, were also studied. The
      G143A mutation caused a high level of resistance to QoI compounds such as
      myxothiazol, axoxystrobin and pyraclostrobin, but not to stigmatellin. The
      pattern of resistance conferred by F129L and L275F was different. Interestingly
      G143A had a slightly deleterious effect on the bc(1) function in V. inaequalis,
      S. fuliginea and P. megasperma Q(o) site mimics but not in that for E. graminis.
      Thus small variations in the Q(o) site seem to affect the impact of the G143A
      mutation on bc(1) activity. Based on this observation in the yeast model, it
      might be anticipated that the G143A mutation might affect the fitness of
      pathogens differentially. If so, this could contribute to observed differences in
      the rates of evolution of QoI resistance in fungal and oomycete pathogens.

PMID- 15153118
TI  - Kinetic studies and molecular modelling attribute a crucial role in the
      specificity and stereoselectivity of penicillin acylase to the pair ArgA145
      ArgB263.
AB  - Kinetic experiments with a substrate series of phenylacetyl-arylamides reveal
      that at least one polar group in the amine moiety is required for the proper
      orientation of the substrate in the large nucleophile-binding subsite of
      penicillin acylase of Escherichia coli. Quantum mechanical molecular modelling of
      enzyme-substrate interactions in the enzyme active site shows that in the case of
      substrates lacking local symmetry, the productive binding implies two
      nonsymmetrical arrangements with respect to the two positively charged
      guanidinium residues of ArgA145 and ArgB263. This indicates a crucial role of the
      specified arginine pair in the substrate- and stereoselectivity of penicillin
      acylase.

PMID- 15153119
TI  - Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor
      site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to
      pCDK2-cyclin A complex.
AB  - The binding of indirubin-5-sulphonate (E226), a potential anti-tumour agent and a
      potent inhibitor (IC(50) = 35 nm) of cyclin-dependent kinase 2 (CDK2) and
      glycogen phosphorylase (GP) has been studied by kinetic and crystallographic
      methods. Kinetic analysis revealed that E226 is a moderate inhibitor of GPb (K(i)
      = 13.8 +/- 0.2 micro m) and GPa (K(i) = 57.8 +/- 7.1 micro m) and acts
      synergistically with glucose. To explore the molecular basis of E226 binding we
      have determined the crystal structure of the GPb/E226 complex at 2.3 A
      resolution. Structure analysis shows clearly that E226 binds at the purine
      inhibitor site, where caffeine and flavopiridol also bind [Oikonomakos, N.G.,
      Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E. & Johnson, L.N.
      (2000) J. Biol. Chem.275, 34566-34573], by intercalating between the two aromatic
      rings of Phe285 and Tyr613. The mode of binding of E226 to GPb is similar, but
      not identical, to that of caffeine and flavopiridol. Comparative structural
      analyses of the GPb-E226, GPb-caffeine and GPb-flavopiridol complex structures
      reveal the structural basis of the differences in the potencies of the three
      inhibitors and indicate binding residues in the inhibitor site that can be
      exploited to obtain more potent inhibitors. Structural comparison of the GPb-E226
      complex structure with the active pCDK2-cyclin A-E226 complex structure clearly
      shows the different binding modes of the ligand to GPb and CDK2; the more
      extensive interactions of E226 with the active site of CDK2 may explain its
      higher affinity towards the latter enzyme.

PMID- 15153122
TI  - Chlorhexidine anaphylaxis: case report and review of the literature.
AB  - Chlorhexidine is a widely used antiseptic and disinfectant. Compared to its
      ubiquitous use in medical and non-medical environments, the sensitization rate
      seems to be low. Multivarious hypersensitivity reactions to the agent have been
      reported, including delayed hypersensitivity reactions such as contact
      dermatitis, fixed drug eruptions and photosensitivity reactions. An increasing
      number of immediate-type allergies such as contact urticaria, occupational asthma
      and anaphylactic shock have been reported. In the case report, we describe
      anaphylaxis due to topical skin application of chlorhexidine, confirmed by skin
      testing and sulfidoleukotriene stimulation test (CAST(R): cellular antigen
      stimulation test). The potential risk of anaphylactic reactions due to the
      application of chlorhexidine is well known, especially that application to mucous
      membranes can cause anaphylactic reactions and was therefore discouraged. The use
      of chlorhexidine at a 0.05% concentration on wounds and intact skin was so far
      thought to be safe. Besides our patient, only one other case of severe
      anaphylactic reaction due to application of chlorhexidine on skin has been
      reported. Hypersensitivity to chlorhexidine is rare, but its potential to cause
      anaphylactic shock is probably underestimated. This review should remind all
      clinicians of an important potential risk of this widely used antiseptic.

PMID- 15153124
TI  - Abstracts of the European Society of Contact Dermatitis 2004 meeting.

PMID- 15153123
TI  - Contact allergy to farnesol in 2021 consecutively patch tested patients. Results
      of the IVDK.
AB  - Farnesol is one of the fragrances considered to be a significant contact
      allergen. Therefore, it was decided by the European Union to label products
      containing farnesol. Farnesol was tested [5% petrolatum (pet.)] together with the
      standard series between 1 January 2003 and 30 June 2003 in 2021 consecutive
      patients, 1243 females and 778 males. Of these, 22 [1.1%, 95% confidence interval
      (CI): 0.7-1.6%] had a positive reaction to farnesol. 147 (8.1%) of those 1825
      tested to Myroxylon pereirae resin (balsam of Peru, 25% pet.) at the same time
      reacted positively, 143 (7.8%) of those 1823 tested to the fragrance mix (FM) (8%
      pet.) and 34 (1.9%) of 1831 tested to propolis (10% pet.). With regard to
      concomitant reactions in farnesol-positive patients, 5 of 22 reacted additionally
      to the FM [odds ratio (OR): 4.3; CI: 1.53-12.15] and 2 (of these 5) additionally
      to M. pereirae resin (OR: 1.27; CI: 0.29-5.54). The strongest association was
      seen to propolis (OR: 6.2; 95% CI: 1.4-27.7). Compared to those with negative
      reactions to farnesol, the group of patients allergic to farnesol was
      characterized by a higher proportion of young females and office workers, and the
      hand and the face were more often affected. In conclusion, farnesol is an
      important allergen. We recommend that farnesol should be included in a fragrance
      patch-test preparation and that its use should be regulated for consumer safety
      reasons. Furthermore, the extent of exposure to farnesol should be further
      studied.

PMID- 15153125
TI  - Conflicts of interest--in publishing and in practice.

PMID- 15153127
TI  - What factors in early pregnancy indicate that the mother will be hit by her
      partner during the year after childbirth? A nationwide Swedish survey.
AB  - BACKGROUND: To be hit by one's intimate partner during the first year after
      childbirth may affect a woman's health and ability to take care of her newborn.
      The purpose of this study was to document the prevalence and indicators in early
      pregnancy of a woman being hit by her partner during the year after childbirth.
      METHOD: Information was collected by a postal questionnaire in early pregnancy
      and 12 months after childbirth from the approximately 5,550 women in Sweden who
      visited an antenatal care clinic for the first time during one of three chosen
      weeks in 1999 and 2000. RESULTS: Of the 3,266 recruited women, 2,563 returned the
      follow-up questionnaire. Being hit during the first year after childbirth was
      reported by 52 of the 2,563 (2%) women: 32 (61%) had been hit by their partner
      once, 12 (23%) twice, and 8 (15%) three or more times. Risk increased in women
      who were age 24 years or younger (3.9% had been hit), unmarried (7.1%), born in
      countries outside Europe (6.8%), with a partner born outside Europe (5.4%), had a
      low level of education (8.9%), and were unemployed (5.0%). In early pregnancy,
      women with back pain (4.0%), a chronic illness (4.1%), coital pain (6.1%),
      frequent depression-related symptoms (8.1%), stomach pain (3.8%), or a urinary
      tract problem (6.3%) were hit more often than others after childbirth.
      CONCLUSIONS: At least 2 percent of Swedish women giving birth in 2000 were hit by
      their partner during the year after childbirth. Using identified predictors
      during antenatal care may increase the likelihood of finding women at risk,
      thereby enhancing the possibility of interventions to prevent this crime and
      health hazard.

PMID- 15153128
TI  - Length of stay after vaginal birth: sociodemographic and readiness-for-discharge
      factors.
AB  - BACKGROUND: The impact of reductions in postpartum length of stay have been
      widely reported, but factors influencing length of hospital stay after vaginal
      birth have received less attention. The study purpose was to compare the
      sociodemographic characteristics and readiness for discharge of new mothers and
      their newborns at 3 discharge time intervals, and to determine which variables
      were associated with postpartum length of stay. METHODS: The study sample
      comprised 1,192 mothers who were discharged within 2 postpartum days after
      uncomplicated vaginal birth at a tertiary perinatal center in the midwestern
      United States. The sample was divided into 3 postpartum length-of-stay groups:
      group 1 (18-30 hr), group 2 (31-42 hr), and group 3 (43-54 hr). Sociodemographic
      and readiness-for-discharge data were collected by self-report and from a
      computerized hospital information system. Measures of readiness for discharge
      included perceived readiness (single item and Readiness for Discharge After Birth
      Scale), documented maternal and neonatal clinical problems, and feeding method.
      RESULTS: Compared with other groups, the longest length-of-stay group was older;
      of higher socioeconomic status and education; and with more primiparous,
      breastfeeding, white, married mothers who were living with the baby's father, had
      adequate home help, and had a private payor source. This group also reported
      greater readiness for discharge, but their newborns had more documented clinical
      problems during the postbirth hospitalization. In logistic regression modeling,
      earlier discharge was associated with young age, multiparity, public payor
      source, low socioeconomic status, lack of readiness for discharge, bottle
      feeding, and absence of a neonatal clinical problem. CONCLUSIONS:
      Sociodemographic characteristics and readiness for discharge (clinical and
      perceived) were associated with length of postpartum hospital stay. Length of
      stay is an outcome of a complex interface between patient, provider, and payor
      influences on discharge timing that requires additional study. Including
      perceived readiness for discharge in clinical discharge criteria will add an
      important dimension to assessment of readiness for discharge after birth.

PMID- 15153129
TI  - Why do some women change their opinion about childbirth over time?
AB  - BACKGROUND: The current investigation is a follow-up of a study on women's memory
      of childbirth, which showed that 60 percent made the same assessment of their
      overall birth experience at 1 year after delivery as they did at 2 months
      postpartum, and 24 percent had became more negative and 16 percent more positive.
      The study purpose was to gain some understanding of what factors make some women
      change their assessment over time. METHODS: Data from a longitudinal cohort study
      of 2,428 women who completed questionnaires in early pregnancy, at 2 months, and
      at 1 year after birth were analyzed. Two subsamples were studied: 1,451 women who
      said childbirth was a positive experience at 2 months and 151 who said it was a
      negative experience. Comparisons were made, within each sample, between those who
      made the same assessment at 1 year and those who had changed their view, with
      respect to psychosocial background, labor outcomes, infant health outcomes during
      first year, and experiences of intrapartum care. RESULTS: Changing the assessment
      from positive to less positive, mostly to "mixed feelings," was associated with
      difficult childbirth, such as painful labor and cesarean section; dissatisfaction
      with intrapartum care; and psychosocial problems, such as single status,
      depressive symptoms, and worry about the birth in early pregnancy. Changing the
      assessment from negative to less negative was associated with less worry about
      the birth in early pregnancy and a more positive experience of support by the
      birth-attending midwife. CONCLUSIONS: This study supported the view that measures
      of satisfaction with childbirth soon after delivery may be colored by relief that
      labor is over and the happy birth of a baby. More negative aspects may take
      longer to integrate. Supportive care may have long-term effects and may protect
      some women from a long-lasting negative experience.

PMID- 15153130
TI  - Women's attitudes toward mode of delivery in South Korea--a society with high
      cesarean section rates.
AB  - BACKGROUND: In South Korea, cesarean section rates (i.e., the proportion of all
      live births delivered by cesarean section) approached 40 percent in 2000. The
      relative contribution of physicians and women to this high rate has been a source
      of debate. This study explored attitudes toward mode of delivery among South
      Korean women. METHODS: A nationwide cross-sectional telephone survey of 505
      Korean women aged 20 to 49 years was conducted using a proportionate quota and
      systematic random sampling method. The response rate was 57.3 percent. Data were
      collected using a structured questionnaire consisting of 7 questions about
      vaginal and cesarean delivery. RESULTS: Over 95 percent of women preferred
      vaginal delivery during pregnancy and were willing to recommend this method to
      others. Of the women who delivered by cesarean section, 10.6 percent stated that
      they had requested a cesarean birth. Attitudes toward vaginal or cesarean
      delivery differed significantly according to a woman's education level.
      CONCLUSIONS: Most study participants showed more favorable attitudes toward
      vaginal delivery than cesarean delivery. This result does not support the
      assumption that the upsurge of cesarean section rates in South Korea is
      associated with women's positive attitudes toward cesarean section. The main
      cause of the rapid rise of cesarean section rates in South Korea during the past
      two decades have its origins in health care practitioners and the health care
      system in which they work.

PMID- 15153131
TI  - Increasing cesarean section rates: exploring the role of culture in an Australian
      community.
AB  - BACKGROUND: The proportion of births by cesarean section in Australia has
      recently increased by 35 percent, rising from 17 percent in 1990 to 23 percent in
      2000. Unlike previous research, which has focused on women's role in increasing
      rates of cesarean section, this study aimed to explore the existence of wider
      cultural norms of acceptance of cesarean section in the Australian community, and
      the implications these might have for rising rates. METHODS: A postal self
      completion questionnaire was sent to a consecutive sample of 148 women who
      delivered 7 weeks earlier at the Women's and Children's Hospital, a tertiary
      referral public maternity hospital in metropolitan Adelaide, South Australia.
      These women were recruited at 18 weeks' gestation, and had been involved in a
      wider study. The questionnaire included three sections, one section on agreement
      with statements pertaining to cultural acceptance of cesarean section, a second
      on personal consideration of cesarean section in early pregnancy, and a third
      including sociodemographic questions. RESULTS: Of the total sample, 92 women
      responded to the questionnaire (response rate 62%). Of 6 items relating to
      community acceptance of cesarean section, responses ranged from 71.4 percent
      agreement ("common for people to think that cesarean section offers an easier way
      of giving birth") to 23.1 percent agreement ("the media seems to portray cesarean
      section as a better option than vaginal delivery"). The option of having a
      cesarean section was considered by almost 15 percent (10/68) of women early in
      their pregnancy. For the vast majority (8/10) this consideration was clinically
      based. CONCLUSIONS: This investigation demonstrated that these Australian women,
      independent of sociodemographic variables such as age and education level, agreed
      that cesarean section was perceived as an easy, convenient way of giving birth.

PMID- 15153132
TI  - Parental attitudes toward breastfeeding: their association with feeding outcome
      at hospital discharge.
AB  - BACKGROUND: A woman chooses to breastfeed for many reasons. Recent research,
      however, suggests that parental attitudes toward breastfeeding are stronger
      predictors of infant feeding choice than commonly cited sociodemographic factors.
      The objective of the current study was to compare the infant feeding attitudes of
      expectant couples, and to determine to what degree their individual attitudes
      during early pregnancy were predictive of the method of infant feeding at
      discharge from hospital. METHODS: A convenience sample of pregnant women
      (gestational age 8-12 weeks), who were attending maternity clinics in Glasgow,
      Scotland, in 2000, completed the 17-item Iowa Infant Feeding Attitude Scale
      (IIFAS), together with their partners. RESULTS: The IIFAS was completed by 108
      expectant couples. At discharge from hospital 49.1 percent of women were
      exclusively breastfeeding, and 50.9 percent were exclusively formula-feeding. A
      woman's total infant feeding attitude score was significantly correlated with her
      partner's score(r = 0.67, p < 0.001). There was no difference in the infant
      feeding attitudes of formula-feeding couples(p = 0.987), but breastfeeding women
      tended to be more supportive of breastfeeding than their partners(p = 0.022).
      Maternal, but not paternal, infant feeding attitude was a significant predictor
      of the choice of feeding method (OR = 1.16 95% CI = 1.09-1.24). CONCLUSIONS:
      Infant feeding attitudes tended to be shared by expectant couples. Maternal
      infant feeding attitude was a better predictor of feeding choice than were
      demographic factors. Paternal attitudes were not found to be independently
      associated with feeding choice. Identification of women with neutral infant
      feeding attitudes using the IIFAS may be an effective way of targeting
      interventions at those women who are most likely to be receptive to such
      programs.

PMID- 15153133
TI  - The role of caregivers after a stillbirth: views and experiences of parents.
AB  - BACKGROUND: The clinical role of the caregiver to parents in the event of a
      stillbirth has yet to be defined. The aim of this paper was to focus on the
      caregivers' support as revealed by the parents' experiences. METHOD: One or both
      parents of 31 stillborn infants (> or =28 weeks) were interviewed twice, for a
      total of 57 interviews. The data analysis was conducted using a qualitative
      approach. RESULTS: Parents identified the caregivers' behavior and handling of
      the stillbirth as important. Findings showed that caregivers should support
      parents in moments of chaos and at other difficult times. The parents needed
      assistance in both facing and separating from the baby. The six "qualities" that
      summarized the findings were "support in chaos,""support in the meeting with and
      separation from the baby,""support in bereavement,""explanation of the
      stillbirth,""organization of the care," and "understanding the nature of grief."
      Findings indicate that the hospital is under an obligation to organize the care
      and make it possible for parents to see the same caregivers again, and to offer
      extra ultrasound investigations and checkups without unnecessary bureaucracy.
      CONCLUSION: We suggest that the "qualities" identified by the study findings
      should be implemented in clinical care, and could facilitate active guidance and
      counseling for bereaved parents who have experienced a stillbirth.

PMID- 15153134
TI  - Anxiety after miscarriage: a review of the empirical literature and implications
      for clinical practice.
AB  - BACKGROUND: Most practitioners now view a miscarriage as a significant
      psychosocial stressor that results in a high level of dysphoria and grief.
      Anxiety, although also commonly present, is less frequently considered and less
      frequently addressed. A review of the empirical literature was conducted to
      determine if anxiety after a miscarriage is elevated, and if risk is increased
      for particular types of anxiety syndromes. An attempt was also made to identify
      the types of interventions that have been found to be helpful in alleviating
      anxiety. METHODS: An electronic search of the Medline and Psych Info databases
      were conducted using the keywords "miscarriage," "perinatal loss," "pregnancy
      loss," "anxiety," "trauma," and "stress." The searches were not intentionally
      circumscribed by date. Further searches were then carried out using references.
      Studies were subsequently included only if most women in a study sample
      experienced the pregnancy loss before 20 weeks' gestation. RESULTS: The
      literature was relatively limited. With respect to level of anxiety after a
      miscarriage, 4 studies were located that employed a matched comparison group
      design, and 3 that employed a follow-up design. Three studies that used a matched
      comparison design were located with respect to an increased risk for particular
      anxiety syndromes. A significant percentage of women experience elevated levels
      of anxiety after a miscarriage up until about 6 months post-miscarriage, and they
      are at increased risk for obsessive-compulsive and posttraumatic stress disorder.
      CONCLUSIONS: Practitioners, as part of routine care after a miscarriage, should
      screen for signs of anxiety as well as depression. When signs of anxiety are
      present, opportunities for catharsis, understanding, and legitimation are likely
      to be helpful, as is reassurance that the stress is likely to appreciably lessen
      over the next 6 months.

PMID- 15153135
TI  - Is your perinatal practice mother-friendly? A strategy for improving maternity
      care.
AB  - The purpose of the questionnaire, "Is Your Perinatal Practice Mother-Friendly?"
      is to provide health practitioners with an evidence-based tool that can be used
      to improve maternity care. The Mother-Friendly Childbirth Initiative is a
      consensus document promoting a wellness model of maternity care that was
      developed by the Coalition for Improving Maternity Services (CIMS) and ratified
      by major childbirth organizations and leading authorities in maternity care. By
      complying with the "Ten Steps of Mother-Friendly Care," a hospital or practice
      can be designated as "mother-friendly." The questionnaire enables health care
      providers to apply the Ten Steps to their maternity practice or services.

PMID- 15153136
TI  - Trends in labor induction in the United States: is it true that what goes up must
      come down?
AB  - Three recent studies examined the national trend in labor induction in the United
      States. All show a doubling in the rate of induction during the 1990s, although
      vital statistics data show a consistently higher trend than that obtained from
      national hospital discharge data. Neither data source adequately documents the
      full range of indications for induction, its timing, hospital staffing
      considerations, and other factors that may play a role. Although rates of
      induction of labor may be leveling off, despite a lack of scientific evidence for
      its widespread use, rates are likely to remain at current levels for the next few
      years.

PMID- 15153139
TI  - Operative delivery and breastfeeding success.

PMID- 15153142
TI  - Medicare reimbursement for destination therapy: the right decision at the right
      time?

PMID- 15153143
TI  - Medicare reimbursement for destination therapy.

PMID- 15153145
TI  - Microencapsulation of parathyroid tissue with photosensitive poly(L-lysine) and
      short chain alginate-co-MPEG.
AB  - Human parathyroid glands were encapsulated using the alginate-PLL system in this
      study. In order to improve the mechanical strength and the biocompatibility, the
      microcapsules were fabricated with a three-layer structure that consisted of
      alginate/photosensitive poly(L-lysine)/short chain alginate-co-MPEG. These
      modified microcapsules were used for encapsulating human parathyroid tissue. In
      vitro experiments revealed that microencapsulated parathyroid glands maintained
      differentiative properties in culture, and the capsular membrane was freely
      permeable to the human parathyroid hormone. For in vivo experiments, these
      capsules were transplanted into parathyroidectomized SD-rats. After
      parathyroidectomy, serum calcium decreased from 2.25 to 1.68 mmol/L and remained
      in a constantly low concentration until transplantation. Parathyroidectomized SD
      rats were normocalcemic after transplant of encapsulated parathyroid tissue. The
      microcapsules were then explanted at 12 weeks for examination. Histological
      evaluations of excised transplants revealed that the microcapsules remained
      intact structurally and were free of cell adhesions. The results demonstrated
      that human parathyroid tissue microencapsulated by this system retains stability
      and is functional both in vitro and in vivo. This encapsulating system will have
      valuable application for endocrine surgery in the future.

PMID- 15153146
TI  - Vascular tone estimation in patients implanted with the AbioCor implantable
      replacement heart.
AB  - The AbioCor implantable replacement heart provides continuous hydraulic pressure
      data that are used for control purposes. The magnitude of the end systolic
      pressure spikes are compared to a preset threshold and used for controlling motor
      speeds to maintain a full stroke on every beat. Portions of the diastolic
      pressures of the left and the right side are averaged and can be used for left
      right balance control. The mean right diastolic pressure may be used for beat
      rate (cardiac output) control. The systolic and diastolic hydraulic pressures of
      the left and right side are correlatable to the respective afterload and preload
      pressures. More importantly, with known hydraulic pump pressure-flow
      characteristics, cardiac output is derived. The slopes of the hydraulic pressure
      traces as a function of time are not used for control or monitoring purposes.
      However, the magnitudes and shapes of these slopes can provide information on the
      tones of a patient's vasculature. The ratio of the slope of the systolic pressure
      to that of the stroke volume yields the vascular tone given in mm Hg/cc. Due to
      pre-existing pulmonary complications, some AbioCor patients have pulmonary
      vascular tones that are substantially higher than their respective aortic tones
      by as much as a factor of four. Pulmonary tones as high as 2 mm Hg/cc, or
      approximately ten times the normal tone, are recorded. The ratio of averages of
      the aortic to the pulmonary tone range between 2.2 and 0.25 in patients implanted
      with the AbioCor compared with a normal value of 5 in subjects without pre
      existing pulmonary diseases. The AbioCor implantable replacement heart's
      hydraulic drive system is capable of providing valuable physiological
      information, including estimates of physiological pressures, cardiac outputs, and
      vascular tones.

PMID- 15153144
TI  - Maintenance of glucose-sensitive insulin secretion of cryopreserved human islets
      with University of Wisconsin solution and ascorbic acid-2 glucoside.
AB  - Normal human islet cells are an ideal source for pancreas-targeted cell
      therapies, but the availability of human donor pancreata for islet isolation is
      severely limited. To effectively utilize such scarce donor organs for cell
      therapies, it is crucial to develop an excellent isolation, effective
      cryopreservation, and efficient gene transfer techniques for the transportation
      of isolated cells. In the present study, we investigate the effect of University
      of Wisconsin (UW) solution and ascorbic acid-2 glucoside (AA2G) on the
      cryopreservation of human islets. We also evaluate the gene transfer efficiency
      of a lentiviral vector expressing the E. coli LacZ gene, Lt-NLS/LacZ, in human
      islets. Human islets were isolated with a standard digestion method at the
      University of Alberta. Isolated islets were transported to Japan for 40 h and
      then subjected to cryopreservation experiments. The following preservation
      solutions were tested: UW solution with 100 micro g/mL of AA2G, UW solution, 100%
      fetal bovine serum (FBS), and CMRL supplemented with 10% FBS. Following three
      months of cryopreservation, the islets were thawed and analyzed for viability,
      glucose-sensitive insulin secretion, proinsulin gene expression profile, and in
      vivo engraftment. The islets were also subjected to monolayer formation with 804G
      cell-line-derived extracellular matrix (ECM), followed by Lt-NLS/LacZ
      transduction. The viability, morphology, glucose-sensitive insulin secretion,
      proinsulin gene expression, and monolayer formation efficiency of the thawed
      cryopreserved islets are significantly better maintained by the use of UW
      solution. When AA2G (100 microg/mL) is combined with UW, such parameters are
      further improved. The adequate engraftment of UW + AA2G-cryopreserved human
      islets is achieved in the liver of nude mice. Efficient Lt-NLS/LacZ transduction
      is identified in monolayered islets cryopreserved with UW solution with AA2G. The
      present work demonstrates that the combination of UW solution with AA2G (100
      microg/mL) would be a useful cryopreservation means for human islets. Human
      islets monolayer-cultured with 804G-derived ECM are efficiently transduced with a
      lentiviral vector Lt-NLS/LacZ.

PMID- 15153147
TI  - Assessment and improvement of the system efficiency for the moving-actuator type
      biventricular assist device.
AB  - This is a test report on the efficiency of a moving-actuator type biventricular
      assist device (AnyHeart, Seoul National University). From the viewpoint of the
      various system mechanisms, the device can be subdivided into three separate
      parts: the motor and its associated controller, the actuator and motor assembly,
      and the blood sac and its associated components (including valves). The motor was
      operated under various conditions, including different torque, angular speed, and
      voltage pulses. The total system efficiency of 8% has been reported before, with
      subpart efficiencies of 50%, 85%, and 19%, respectively, for the motor and its
      associated controller, the actuator and motor assembly, and the blood sac and its
      associated components (including valves), under normal operating conditions (4
      L/min pump output, 100 mm Hg aortic pressure [AoP]). This article focuses on the
      method of analyzing and improving the system efficiency. The applied input
      voltage under the normal operating conditions of the pump was determined using
      the analyzed results. Also, a speed profile that takes into consideration the
      filling state of the blood sac was provided. On the basis of tests performed
      involving in vitro mock circulation, experimental results are provided to
      demonstrate the effectiveness of the approach presented in this article.

PMID- 15153149
TI  - Flow visualization in a centrifugal blood pump with an eccentric inlet port.
AB  - Flow visualization analysis was applied to the Baylor/Miwatec centrifugal
      artificial heart to evaluate its fluid dynamic characteristics regarding
      antithrombogenicity. An eccentric vortex was found both in the upper and the
      lower gaps of the impeller, which is supposed to be caused by the eccentric inlet
      port. Therefore, one-way flow toward the outlet is formed and washes the pivot.
      The combination of an eccentric vortex and a pivot bearing that is washed is
      unique to the Baylor/Miwatec pump. For the male pivots exposed to periodic wash,
      the minimum shear rate around the bottom pivot was estimated to be 650/s, which
      is higher than the threshold for thrombus formation shown by other studies. The
      wall shear rate at the impeller bottom surface was found to be larger in the top
      contact mode than in the bottom contact mode.

PMID- 15153148
TI  - Centrifugal blood pump with a hydraulically-levitated impeller for a permanently
      implantable biventricular assist device.
AB  - A permanently implantable biventricular assist device (BVAD) system has been
      developed with a centrifugal pump which is activated by a hydraulically-levitated
      impeller. The pump impeller floats hydraulically into the top contact position;
      this position prevents thrombus formation by creating a washout effect at the
      bottom bearing area, a common stagnant region. The pump was subjected to in vitro
      studies using a pulsatile mock circulation loop to confirm the impeller's top
      contact position and the swinging motion produced by the pulsation. Eleven in
      vivo BVAD studies confirmed that this swinging motion eliminated blood clot
      formation. Twenty-one pumps im-planted for up to three months did not reveal any
      thrombosis in the pumps or downstream organs. One exception was a right pump
      which was exposed to severe low flow due to the kinking of the outflow graft by
      the accidental pulling of the flow meter cable. Three ninety-day BVAD studies
      were achieved without thrombus formation.

PMID- 15153150
TI  - Effects of customized bicarbonate buffered solutions for continuous renal
      replacement therapies on polymorphonuclear leukocytes function and viability.
AB  - It has previously been shown that the mixture of bicarbonate and calcium in the
      solutions used for continuous renal replacement therapy led to crystallization
      and significant changes in calcium concentration and pH. The aim of this study
      was to investigate the impact of bicarbonate/calcium and lactate/calcium
      solutions for Continuous Renal Replacement Therapies (CRRT) on the viability and
      function of polymorphonuclear cells (PMN). We tested four customized bicarbonate
      buffered solutions: single bag (bicarbonate and calcium mixed 24 h before
      testing), double bag (mixed immediately before testing), filtered single bag and
      double bag solutions, and a commercial lactate buffered solution. Blood from 6
      volunteers was incubated with the solutions for 30 min followed by PMN isolation.
      After overnight incubation, viability, phagocytosis, and peroxide production by
      PMN were determined by flow cytometry. There was no difference between the test
      solutions with respect to PMN viability and function. Therefore, the presence of
      microcrystals and the consequent changes in electrolyte concentrations do not
      seem to impair PMN function.

PMID- 15153151
TI  - The orthotic effect of functional electrical stimulation on the improvement of
      walking in stroke patients with a dropped foot: a systematic review.
AB  - OBJECTIVE: Analysis of the available evidence on the improvement of walking in
      stroke patients with a dropped foot when using peroneus stimulation. METHODS: A
      systematic review was performed to identify trials that investigated the orthotic
      effect of functional electrical stimulation (FES) on walking in stroke patients
      with a dropped foot. Two independent raters scored the methodological quality of
      the included articles. Walking speed and physiological cost index (PCI) were
      selected as the primary outcome measures. Studies that measured walking speed
      were pooled and a pooled difference including confidence interval was calculated.
      RESULTS: Eight studies were included in the review, of which one was a randomized
      controlled trial. Methodological score ranged from 8 to 18 out of 19. Six studies
      measured walking speed. The pooled improvement in walking speed was 0.13 m/s
      (0.07-0.2) or 38% (22.18-53.8). CONCLUSIONS: The present review suggests a
      positive orthotic effect of functional electrical stimulation on walking speed.

PMID- 15153152
TI  - Bridge-to-recovery from acute myocarditis in a 12-year-old child.
AB  - Fulminant myocarditis causes substantial morbidity and mortality, especially in
      children and young adults. Mechanical circulatory support has become the standard
      therapy to bridge patients with intractable heart failure to either
      transplantation or myocardial recovery. Yet, successful weaning from
      biventricular support with full recovery is extremely rare in the pediatric
      population. This report describes the successful use of the MEDOS HIA ventricular
      assist device to bridge a 12-year-old girl to myocardial recovery in a
      biventricular bypass configuration. The left and right ventricle were completely
      off-loaded by the pumps and the device provided sufficient cardiac output to
      normalize end-organ function. Anticoagulation was maintained with i.v. heparin
      infusion. No neurological complications were detectable and the pump system was
      free of any macroscopic thrombi. After 19 days of support, cardiac function had
      recovered and the patient was successfully weaned from the device. Following
      physical rehabilitation, the patient was discharged home.

PMID- 15153153
TI  - The bactericidal effects of electrolyzed oxidizing water on bacterial strains
      involved in hospital infections.
AB  - The study is designed to investigate bactericidal actions of electrolyzed
      oxidizing water on hospital infections. Ten of the most common opportunistic
      pathogens are used for this study. Cultures are inoculated in 4.5 mL of
      electrolyzed oxidizing (EO) water or 4.5 mL of sterile deionized water (control),
      and incubated for 0, 0.5, and 5 min at room temperature. At the exposure time of
      30 s the EO water completely inactivates all of the bacterial strains, with the
      exception of vegetative cells and spores of bacilli which need 5 min to be
      killed. The results indicate that electrolyzed oxidizing water may be a useful
      disinfectant for hospital infections, but its clinical application has still to
      be evaluated.

PMID- 15153154
TI  - Selective adsorption of homocysteine using an HFR-ON LINE technique.
AB  - HFR-ON LINE (double chamber HDF with reinfusion of ultrafiltrate regenerated
      through a charcoal-resin cartridge) is a novel method which combines the
      processes of diffusion, convection, and adsorbance. We have investigated the
      effect of such a treatment on the homocysteine (Hcy) levels in ten patients with
      a mean Hcy level of 57.6 micromol/L (range 24.1-119.7 micromol/L). We have
      measured the Hcy, folate, and vitamin B12 predialysis and postdialysis, and in
      the ultrafiltrate precartridge and postcartridge at 10, 120, and 240 min. The
      mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3 micromol/L) (P =
      0.005) predialysis and postdialysis, respectively, while folate and vitamin B12
      were unchanged. Precartridge and postcartridge Hcy levels were 11.6 vs. 2.5
      micromol/L (P = 0.005), 9.3 vs. 3.9 micromol/L (P = 0.005), and 7.7 vs. 4.6 micro
      mol/L (P = 0.012) at the three time points considered, while folate and vitamin
      B12 were essentially undetectable. These preliminary data, which need
      confirmation in a long-term study, seem to indicate that HFR-ON LINE is able to
      reduce Hcy levels not only through a likely reduction of uremic toxins, but also
      through an actual removal of Hcy by adsorbance onto the charcoal-resin cartridge.

PMID- 15153155
TI  - Clinicopathological aspects of 18 Kaposi's sarcoma among 1055 Greek renal
      transplant recipients.
AB  - The incidence of Kaposi's sarcoma (KS) in transplant recipients is 400-500 times
      greater than that in the general population, and is rising within the transplant
      population. In this study, between March 1983 and December 2001, 1055 cases were
      recorded where KS developed in 18 patients (1.7%) who were treated with AZA + CsA
      + MP, MMF + CsA + MP, MMF + Tac + MP, CsA + MP, or AZA + MP therapy (AZA,
      azathioprine; CsA, cyclosporine A; MP, methylprednisolone; MMF, mycophenolate
      mofetil; Tac, Tacrolimus). In the present study, 18 renal transplant recipients
      who developed KS and were followed and analyzed. Analysis revealed that a
      continuous state of immunodeficiency is important for the development of KS.
      Prognosis in patients with KS limited to the skin is favorable, while visceral
      involvement is associated with high mortality. Transplant function is well
      preserved in most of the cases. The association, previously described, between
      human herpesvirus 8 (HHV8) and transplant-associated KS also exists in the
      studied population.

PMID- 15153157
TI  - Integrons and multidrug resistance among Escherichia coli causing community
      acquired urinary tract infection in southern India.
AB  - Antimicrobial resistance genes are often clustered in integrons, genetic elements
      capable of recombination. There is a paucity of data on the prevalence and role
      of integrons from community-acquired infections in developing countries where
      resistance to co-trimoxazole is high. We determined the prevalence of integrons
      among Escherichia coli causing community-acquired urinary tract infection (UTI).
      Consecutive isolates of E. coli obtained from UTI of pregnant women at the
      Christian Medical College Hospital, Vellore, India, during 2002 were included.
      All isolates were tested for susceptibility to 16 antimicrobials using the disc
      diffusion method and for integrons of classes 1 and 2 by PCR. Of the 58 isolates
      tested, 28 (48.3%) were resistant to co-trimoxazole and trimethoprim. All these
      isolates carried integrons. Three additional isolates were sulfonamide resistant
      but integron negative. Class 1 integrons were present in 21 (36.2%) isolates.
      Resistance to ampicillin (p=0.000), nalidixic acid (p=0.001), chloramphenicol
      (p=0.02), tetracycline (p=0.004) and gentamicin (p=0.02) was significantly more
      common in isolates with integrons. DNA sequencing of two isolates with integrons
      showed the presence of aadA, dfr1 and dfr7 genes. This study demonstrated that
      integrons are widely prevalent in India and that they might play a role in
      multidrug resistance in E. coli from community-acquired UTI.

PMID- 15153158
TI  - Geographically dependent distribution of gyrA gene mutations at codons 83 and 87
      in Salmonella Hadar, and a novel codon 81 Gly to His mutation in Salmonella
      Enteritidis.
AB  - In all, 90 nalidixic acid-resistant clinical strains of Salmonella Hadar and
      Salmonella Enteritidis isolated in Norway but of predominantly foreign origin
      were subjected to sequencing of the gyrA, gyrB, parC and parE genes. All the
      isolates contained at least one mutation in gyrA codon 83 or codon 87. A highly
      significant correlation between mutations in gyrA codon 83 and strains
      originating from Southeast Asia was found in S. Hadar but not in S. Enteritidis.
      A novel gyrA codon 81 Gly to His mutation was discovered in one S. Enteritidis
      isolate. One amino-acid (aa) changing mutation was found outside the quinolone
      resistance-determining region (QRDR) of S. Hadar parC at codon 57, which has
      previously only been observed once in Salmonellae.

PMID- 15153159
TI  - The regulation of rhinovirus infection in vitro by IL-8, HuIFN-alpha, and TNF
      alpha.
AB  - The influence of three important cytokines (IL-8, TNF-alpha, and HuIFN-alpha) on
      ongoing rhinovirus infections has been examined in vitro, individually or as
      combinations. TNF-alpha was able to transform traces of HRV infections into full
      blown infections. Furthermore, TNF-alpha was able to down-regulate the antiviral
      action of HuIFN-alpha completely, even at levels of just a few pg/ml. This
      suggests that the induction of TNF-alpha by HRV may be part of the virus's
      strategy to minimize the interferon response which is part of the host's immune
      defence system. However, troxerutin (a flavonoid) was able to neutralize the
      downregulatory action of TNF-alpha on the HuIFN-alpha system at low levels and re
      establish the antiviral activity ascribed to IFN-alpha. IL-8 exerted a minor
      influence on the interferon system, and had no influence on rhinovirus
      infections. The in vitro findings are supported, in part, by recent in vivo
      findings in a common cold pilot study.

PMID- 15153160
TI  - Multilocular cystic renal cell carcinoma: a clinicopathological, immuno- and
      lectin histochemical study of nine cases.
AB  - Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon variant of renal
      neoplasm and its histogenesis is unclear. The aim of this study was to use immuno
      and lectin histochemistry to delineate histochemical patterns which might
      indicate the histogenetic origin of MCRCC from a particular part or parts of the
      nephron. We present our experience with nine cases of MCRCC. Fifteen cases of
      renal cell carcinoma with cystic degeneration (RCC-CD) were selected for
      comparison with MCRCC. We carried out clinicopathological and immunohistochemical
      examinations of the MCRCC cases. Clinically, the prognosis of the patients was
      quite good, in that all nine patients are alive and without recurrence at the
      time of this report. The MCRCCs reacted strongly in a higher proportion of cases
      with the distal nephron markers, such as peanut agglutinin (PNA, 88.9%) and MUC1
      core antibody (MUC1, 100%), but none reacted preferentially with proximal nephron
      markers such as vimentin, Leu M1 and Lotus tetragonolobus (LTA). The RCC-CD
      tumours reacted with vimentin (40%), Leu M1 (66.7%) and LTA (86.7%). Except for
      two cases, the RCC-CD tumours did not react with PNA or MUC1 core antibody. These
      results illustrate the different patterns of expression of MCRCC and RCC-CD and
      suggest that MCRCC originates from the distal nephron. Therefore, MCRCC should be
      differentiated from other types of renal cell carcinoma on the basis of the
      histogenesis of the tumour and the clinicopathological findings.

PMID- 15153161
TI  - Early segmental changes in ischemic acute tubular necrosis of the rat kidney.
AB  - The background and mechanisms of ischemic acute tubular necrosis are still
      essentially unclarified. Therefore a quantitative morphological technique was
      applied for evaluation of the early structural changes in different fractions of
      the proximal convoluted tubule in the rat renal cortex. In male pentothal
      anesthetized Wistar rats (body weight 200-250 g) ischemia of the right kidney was
      obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for
      varying periods of time (10 min to 6 h) followed by removal and instant freezing
      of the kidney in isopentane at -165 degrees C and subsequent freeze-substitution
      in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS
      stained. In the segments of the proximal convoluted tubules of the nephrons,
      presence of nuclear pyknosis, places of denuded basement membranes and presence
      of exfoliated tubular cells were counted. The results were statistically treated
      for comparison between the extent of damage in the initial postglomerular
      fraction and the later tubular loops. All three parameters showed a systematic,
      statistically significant increased number of lesions in the initial fraction of
      the proximal convoluted tubule versus the subsequent loops. The distribution of
      the structural lesions is in accordance with the previously reported presence of
      a tubulo-capillary counter-current flow in the proximal convoluted tubule and,
      when related to the highly variable oxygen tension in the normal renal cortex of
      the rat, indicates that the peculiar location of the early lesions might well be
      determined by these functional conditions.

PMID- 15153162
TI  - Antiangiogenic effect of metronomic paclitaxel treatment in prostate cancer and
      non-tumor tissue in the same animals: a quantitative study.
AB  - Well-tolerated continuous or metronomic chemotherapy can exert a marked
      antiangiogenic and thus superior antitumor effect compared with conventional high
      dose, temporarily spaced-out chemotherapy, as shown in preclinical studies. There
      is, however, no means of directly assessing the antiangiogenic effect in a tumor,
      a serious impediment to assessing the effects of putative antiangiogenic
      chemotherapeutics or treatments. In an attempt to circumvent or minimize this
      impediment we studied the antiangiogenic effect of well-tolerated metronomic
      paclitaxel therapy in a surrogate tumor-free tissue that allows true quantitative
      analysis as well as in syngeneic At-1 prostate cancer in the same rat. This novel
      model allows an accurate comparison of the angiogenesis-modulating effect of
      chemotherapy in the two tissues to be made. The effect of chemotherapy on VEGF-A
      mediated angiogenesis, a characteristic of most tumors, was assessed truly
      quantitatively by microscopic morphometry and image analysis in the tumor-free
      mesentery. The chemotherapy significantly suppressed VEGF-A-mediated angiogenesis
      in the mesentery to an extent that closely mirrored the significant increase in
      tumor necrosis measured morphometrically and the significant decrease in tumor
      growth rate. This finding opens an avenue to study quantitatively and
      systematically the antiangiogenic effect of chemotherapeutic modalities and
      treatments that approximately mirror their antiangiogenic effect in the At-1
      tumor.

PMID- 15153163
TI  - A hospital-associated outbreak of Legionnaires' disease caused by Legionella
      pneumophila serogroups 4 and 10 with a common genetic fingerprinting pattern.
AB  - An outbreak of eight cases of pneumonia caused by Legionella pneumophila non
      serogroup 1 (non-sg 1) occurred at a Swedish university hospital in 1993.
      Including previous and subsequent sporadic cases, the total number of culture
      positive patients was 13. Twelve available non-sg1 isolates from patients were
      compared to 50 environmental water isolates using a monoclonal antibody test for
      serogrouping and amplified fragment length polymorphism analysis (AFLP). Of the
      12 hospital-associated Legionella non-sg 1 patient isolates, 4 were serogrouped
      as sg 4, 7 as sg 10, and one as sg 6. Using AFLP fingerprinting all serogroup
      (sg) 4 and 10 isolates were genetically related except for minor variations.
      Furthermore, sg 4 isolates were identical in AFLP to sg 10 isolates. Patient
      isolates were also identical to isolates found in the water system of several
      hospital buildings, but quite unrelated to isolates obtained in a subsequent
      outbreak at the same hospital caused by L. pneumophila sg 1. Serogroup variations
      in outbreaks may occur despite a common molecular fingerprinting pattern.
      Evidently, the L. pneumophila sg 4 and 10 strains were closely related
      genetically, which raises the question whether this variation in phenotype is due
      to a genetic event or to a variable phenotypic expression. Genetic fingerprinting
      should be used in conjunction with serogrouping in epidemiological
      investigations.

PMID- 15153164
TI  - Localized peribronchial adenomyomatous hyperplasia arising from an ectatic
      bronchus with aspergilloma.
AB  - A cavitary lesion containing a mobile nodule was found in the right lower lung of
      a 68-year-old woman. Suspecting bronchiectasis with a fungus ball, we performed
      wedge resection of the right lower lobe. Light microscopy revealed that a
      uniformly thickened muscular layer around the ectatic bronchus with aspergilloma
      had formed a focally protruding mass. It was composed of bundles of hyperplastic
      smooth muscle and entrapped glandular structures. Given the histological
      similarity between the lesion and adenomyomatous hyperplasia of the gallbladder,
      we diagnosed the previously undescribed lesion as "localized peribronchial
      adenomyomatous hyperplasia". This condition should be recognized as a tumor-like
      form of smooth muscle hyperplasia induced by bronchiectasis and inflammation.

PMID- 15153165
TI  - A rare course of Whipple's disease with atypical cardiac manifestation.
AB  - Whipple's disease (WD) is a rare disorder caused by the gram-positive
      actinomycete Tropheryma whippelii (1). An oral route of acquisition is presumed
      (2). WD is a chronic systemic infection morphologically characterized by foamy
      PAS-positive macrophages. This case report depicts the diagnosis and clinical
      management of a woman who presented with atypical cardial manifestations of WD
      and died from severe cardiac impairment by Tropheryma whippelii which was
      confirmed by polymerase chain reaction. Histological assessment of myocardial
      specimens obtained at autopsy showed PAS-positive macrophages accumulating within
      foci of interstitial myocardial fibrosis. Immunohistochemical staining
      demonstrated myocarditis with lymphocytes and neutrophilic granulocytes, which
      has not been reported so far in the course of WD.

PMID- 15153166
TI  - Review article: Deoxyribonucleic acid-based diagnostic techniques to detect
      Helicobacter pylori.
AB  - Helicobacter pylori is an important cause of many gastrointestinal disorders,
      ranging from chronic gastritis to gastric lymphoma and adenocarcinoma. The
      deoxyribonucleic acid-based assays have the potential to be a powerful diagnostic
      tool given its ability to specifically identify H. pylori deoxyribonucleic acid.
      Markers used to include general H. pylori structures and pathogenetic factors
      like ureaseA, cagA, vacA, iceA. Deoxyribonucleic acid or bacterial ribonucleic
      acid for polymerase chain reaction assays can be collected from gastric biopsy,
      gastric juice, stool, buccal specimens. Polymerase chain reaction can yield
      quantitative and genotyping results with sensitivity and specificity that
      approaches 100%. A clear trend in the direction of the determination of
      quantitative H. pylori infection by real-time polymerase chain reaction can be
      observed. Fluorescent in situ hybridization is suggested for routine antibiotic
      resistance determination. To identify the organism, deoxyribonucleic acid
      structure and its virulence factors may be feasible by using oligonucleotide
      microarray specifically recognizing and discriminating bacterial deoxyribonucleic
      acid and various virulence factors. Deoxyribonucleic acid-based H. pylori
      diagnosis yields higher sensitivity, however, specificity requires sophisticated
      labour environment and associated with higher costs.

PMID- 15153167
TI  - Randomized controlled azathioprine withdrawal after more than two years treatment
      in Crohn's disease: increased relapse rate the following year.
AB  - INTRODUCTION: Azathioprine is effective for maintenance of remission in Crohn's
      disease, however, duration of efficacy and the dose response relationship has not
      been fully evaluated. AIMS: To investigate whether patients kept in remission by
      azathioprine treatment for >2 years benefit from further treatment, and to
      explore dose-response relationship. PATIENTS AND METHODS: In an open 12-month
      trial, patients with inactive Crohn's disease after >2 years (median 37 months)
      of azathioprine treatment were randomized to azathioprine withdrawal or continued
      treatment. Primary end point was relapse defined as: (i) Crohn's disease activity
      index rise >/= 75, and Crohn's disease activity index >150 or (ii) disease
      activity requiring intervention. RESULTS: Of 29 patients, 28 completed the
      observation period or relapsed. Eleven of 13 patients (85%) continuing
      azathioprine remained in remission compared with seven of 15 (47%) observed
      without azathioprine (P = 0.043). In patients who had been treated with
      azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of
      nine (89%) vs. four of 12 (33%) respectively (P = 0.017). CONCLUSIONS: Patients
      with Crohn's disease in remission after >2 years of continuous azathioprine
      treatment will benefit from further continued treatment. Further controlled
      studies with azathioprine doses <2.0 mg/kg/day are needed.

PMID- 15153168
TI  - Outcome of emergency ERCP for acute cholangitis in patients 90 years of age and
      older.
AB  - BACKGROUND: An increasing proportion of the general population across the Western
      World now survives to an advanced age. However, there is limited data on the
      outcome of therapeutic endoscopic retrograde cholangiopancreatography in patients
      above 90 years of age with severe acute cholangitis. AIM: To determine the
      relative frequency of postendoscopic retrograde cholangiopancreatography
      complication in this group of patients. METHODS: The postendoscopic retrograde
      cholangiopancreatography complications related outcome of 64 patients aged 90
      years and above (Group 1) with severe acute cholangitis were retrospectively
      compared with 165 patients under the age of 90 years (Group 2). RESULTS: The
      postendoscopic retrograde cholangiopancreatography complication rate was 4.7%
      (three patients) in Group 1 and 7.3% (12 patients) in Group 2. There was no
      significant difference in the postendoscopic retrograde cholangiopancreatography
      complication rate between the two groups (P = 0.567). The relative frequency of
      30-day mortality was 7.8% (five patients) in Group 1 and 4.2% (seven patients) in
      Group 2 (P = 0.227). CONCLUSION: Urgent biliary decompression with endoscopic
      retrograde cholangiopancreatography in patients 90 years of age and older with
      severe acute cholangitis is a safe and effective procedure in the hands of highly
      skilled endoscopists and is not associated with increased morbidity or mortality
      even in this group of high risk patients.

PMID- 15153169
TI  - Cost-effectiveness of screening for hepatocellular carcinoma in patients with
      cirrhosis due to chronic hepatitis C.
AB  - BACKGROUND: Screening for hepatocellular carcinoma in cirrhotic patients using
      abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM:
      To evaluate its cost-effectiveness using a Markov decision model. METHODS:
      Several screening strategies with abdominal ultrasonography or computerized
      tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old
      patients with chronic hepatitis C and compensated cirrhosis were simulated from a
      societal perspective, resulting in discounted costs per quality-adjusted life
      year saved. Extensive sensitivity analysis was performed. RESULTS: For the least
      efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental
      cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life
      year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used
      strategy in the United States, was more efficacious, with a cost-effectiveness
      ratio of $33 083/quality-adjusted life-year vs. annual alpha
      foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha
      foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73
      789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual
      ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography
      screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life
      year vs. biannual alpha-foetoprotein/annual ultrasonography screening.
      CONCLUSIONS: Screening for hepatocellular carcinoma is as cost-effective as other
      accepted screening protocols. Of the strategies evaluated, biannual alpha
      foetoprotein/annual ultrasonography gives the most quality-adjusted life-year
      gain while still maintaining a cost-effectiveness ratio <$50 000/quality-adjusted
      life-year. Biannual alpha-foetoprotein/annual computerized tomography screening
      may be cost-effective.

PMID- 15153171
TI  - Long-term effect of Helicobacter pylori eradication on the reversibility of acid
      secretion in profound hypochlorhydria.
AB  - BACKGROUND: Although profound hypochlorhydria is considered to be an important
      risk factor for development of gastric cancer, long-term effect of Helicobacter
      pylori eradication on its reversibility remains uncertain. AIM: To clarify the
      change in acid secretion after eradication in a long-term follow-up over 5 years
      in patients with profound hypochlorhydria. METHODS: Twenty-three H. pylori
      positive patients with hypochlorhydria (<0.6 mmol/10 min) were enrolled
      prospectively. Assessment of gastrin-stimulated acid output and histologic
      evaluation of biopsy specimens were performed prior to, and 1, 7 months after
      eradication. Subsequently, gastric acid secretion was assessed for long-term
      period over 5 years after eradication in 12 patients. RESULTS: Gastric acid
      secretion was reversed to normal range in nine of 23 patients (39%) at 7 months
      after eradication. In the long-term follow-up, gradual and significant recovery
      in gastric acid secretion was observed up to 2 years post-therapy. However, there
      was no additional increase during the last 3 years of 5-year follow-up period,
      leaving the acid secretory levels subnormal in the majority of the patients.
      CONCLUSIONS: This long-term follow-up study suggests that the pathologic process
      has already progressed to an irreversible stage in the majority of H. pylori
      positive patients with marked body atrophy and profound hypochlorhydria.

PMID- 15153170
TI  - Cholesterol lowering effect of dietary weight loss and orlistat treatment-
      efficacy and limitations.
AB  - BACKGROUND: Orlistat reduces energy uptake by the impairment of fat digestion and
      some evidence indicates it also lowers plasma cholesterol. AIM: To examine total,
      low-density lipoprotein- and high-density lipoprotein cholesterol during a weight
      reducing regimen, and assess the effect of orlistat in lowering cholesterol
      levels independent of its weight reducing efficacy. METHODS: A total of 448
      patients with elevated cholesterol according to cardiovascular risk factors
      entered a 2 week single-blind run-in period on a hypocaloric diet. Of 384
      patients were subsequently assigned double-blind treatment with orlistat (3 x 120
      mg/day) or placebo for 6 months in conjunction with the hypocaloric diet.
      RESULTS: Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo.
      Total and low-density lipoprotein cholesterol decreased by 25-30 mg/dL vs. 10-15
      mg/dL with placebo. Reduction of cholesterol with orlistat was significantly
      greater than anticipated from weight loss alone. In patients with cardiovascular
      risk factors entering the study with lower cholesterol values orlistat was also
      superior to placebo. On the contrary, reduction of cholesterol concentrations
      never exceeded 20%. CONCLUSION: Orlistat has a cholesterol lowering efficacy
      independent of its weight reducing effect. Because of the limited therapeutic
      effectiveness, patients at high cardiovascular risk should receive rather early
      additional cholesterol lowering medication during weight loss programmes.

PMID- 15153172
TI  - Reduced incidence of gastroduodenal ulcers associated with lumiracoxib compared
      with ibuprofen in patients with rheumatoid arthritis.
AB  - BACKGROUND: Lumiracoxib (Prexige; Novartis Pharma AG, Basel, Switzerland) is a
      cyclooxygenase-2 selective inhibitor associated with improved gastrointestinal
      safety compared with nonsteroidal anti-inflammatory drugs, in patients with
      osteoarthritis. AIM: To compare the gastroduodenal safety of lumiracoxib with
      ibuprofen and celecoxib in patients with rheumatoid arthritis. METHODS: A total
      of 893 patients with rheumatoid arthritis were randomized to lumiracoxib 400 mg
      once daily, lumiracoxib 800 mg once daily, ibuprofen 800 mg three times daily or
      celecoxib 200 mg twice daily for 13 weeks, in a double-blind randomised
      controlled clinical trial. The primary endpoint was the cumulative incidence of
      gastroduodenal ulcers over 13 weeks. RESULTS: The incidence of gastroduodenal
      ulcers >/=3 mm with lumiracoxib 400 mg once daily (2.8%) or lumiracoxib 800 mg
      once daily (4.3%) was significantly lower than with ibuprofen (13.6%, all P <
      0.01) and not different from celecoxib (1.9%). The incidence of adverse events
      was similar for lumiracoxib 400, 800 mg and celecoxib (78, 75 and 77%,
      respectively) and higher with ibuprofen (86%). Discontinuation for adverse events
      was highest for ibuprofen (12.5% vs. 7.9-8.8% for the other groups). CONCLUSIONS:
      Lumiracoxib demonstrated gastroduodenal safety superior to ibuprofen and similar
      to celecoxib in patients with rheumatoid arthritis.

PMID- 15153173
TI  - Serological testing for coeliac disease in patients with symptoms of irritable
      bowel syndrome: a cost-effectiveness analysis.
AB  - BACKGROUND: Patients diagnosed with irritable bowel syndrome may have coeliac
      disease. AIM: To evaluate the cost-effectiveness of coeliac disease testing in
      suspected irritable bowel syndrome. METHODS: We used decision analysis to
      estimate the number of coeliac disease cases detected, quality-adjusted life
      years gained, and costs resulting from testing suspected irritable bowel syndrome
      patients for tissue transglutaminase antibody or an antibody panel (tissue
      transglutaminase, gliadin, total immunoglobulin A). Positive tests prompted
      endoscopic biopsy. A gluten-free diet improved quality of life in coeliac
      disease. RESULTS: Assuming a coeliac disease prevalence of 3%, tissue
      transglutaminase detected 28 and the panel detected 29 of 30 coeliac disease
      cases among 1000 suspected irritable bowel syndrome patients. The cost/case
      detected was $4600 with tissue transglutaminase and $8800 with the panel. The
      cost/quality-adjusted life-year gained with tissue transglutaminase was $7400,
      and the incremental cost/quality-adjusted life-year gained for the panel vs.
      tissue transglutaminase was $287 000. Tissue transglutaminase cost under $100
      000/quality-adjusted life-year gained at a coeliac disease prevalence >/=1.1%,
      assuming a modest utility gain of 0.005 with coeliac disease diagnosis.
      CONCLUSIONS: Testing for coeliac disease in patients with suspected irritable
      bowel syndrome is likely to be cost-effective even at a relatively low coeliac
      disease prevalence and with small improvements in quality of life with a gluten
      free diet.

PMID- 15153174
TI  - A novel option for dosing of proton pump inhibitors: dispersion of lansoprazole
      orally disintegrating tablet in water via oral syringe.
AB  - BACKGROUND: A new formulation of lansoprazole, the lansoprazole orally
      disintegrating tablet, rapidly disintegrates in water eliminating the need for
      swallowing whole pills. AIM: To assess the effect that dispersing the
      lansoprazole orally disintegrating tablet in water would have on lansoprazole
      pharmacokinetics. METHODS: Forty healthy adult men and women (18-43 years)
      received two single 15 mg lansoprazole orally disintegrating tablet doses
      separated by 3 days (one administered directly onto the tongue without water and
      one dispersed in water and administered orally via syringe) in a randomized,
      crossover fashion. Serial plasma samples were determined from 0 to 12 h for each
      dose. Ratios of central values for peak plasma exposure (C(max)) and mean overall
      extent of exposure (area under the plasma concentration) were used to compare the
      bioavailability. RESULTS: The two dosing regimens were bioequivalent, with the
      point estimate for area under the plasma concentration equalling 1.080
      (confidence interval 1.012-1.152) and the point estimate for C(max) equalling
      1.082 (confidence interval 0.961-1.218). CONCLUSIONS: Dispersing the 15 mg
      lansoprazole orally disintegrating tablet in water and administering the dose
      orally via syringe is bioequivalent to the 15 mg intact lansoprazole orally
      disintegrating tablet with respect to lansoprazole area under the plasma
      concentration and C(max). This dosing route provides an additional, convenient
      dosing option for lansoprazole.

PMID- 15153175
TI  - A population-based epidemiologic study of irritable bowel syndrome in South
      China: stratified randomized study by cluster sampling.
AB  - BACKGROUND: The detailed population-based data on irritable bowel syndrome in
      South China are lacking. AIMS: To assess the prevalence of irritable bowel
      syndrome in South China and its impact on health-related quality of life.
      SUBJECTS AND METHODS: A face-to-face interview was carried out in South China to
      assess the prevalence of irritable bowel syndrome. Random clustered sampling of
      permanent inhabitants aged 18-80 years was carried out under stratification of
      urban and suburban areas. The impact of irritable bowel syndrome on health
      related quality of life was evaluated using the Chinese version of SF-36.
      RESULTS: A total of 4178 subjects (1907 male and 2271 female) were interviewed.
      The adjusted prevalence of irritable bowel syndrome in South China is 11.50%
      according to the Manning criteria and 5.67% according to the Rome II criteria.
      Factors including history of analgesic use such as non-steroidal anti
      inflammatory drug (odds ratio 3.83), history of food allergies (odds ratio 2.68),
      psychological distress (odds ratio 2.18), life events (odds ratio 1.89), history
      of dysentery (odds ratio 1.63) and negative coping style (odds ratio 1.28) were
      significantly associated with the presence of irritable bowel syndrome (P <
      0.05). Irritable bowel syndrome was significantly associated with a decrement in
      health-related quality of life score. CONCLUSION: Irritable bowel syndrome is a
      common disorder in South China and has a negative impact on health-related
      quality of life.

PMID- 15153176
TI  - Uncoupled and surviving: individual mice with high metabolism have greater
      mitochondrial uncoupling and live longer.
AB  - Two theories of how energy metabolism should be associated with longevity, both
      mediated via free-radical production, make completely contrary predictions. The
      'rate of living-free-radical theory' (Pearl, 1928; Harman, 1956; Sohal, 2002)
      suggests a negative association, the 'uncoupling to survive' hypothesis (Brand,
      2000) suggests the correlation should be positive. Existing empirical data on
      this issue is contradictory and extremely confused (Rubner, 1908; Yan & Sohal,
      2000; Ragland & Sohal, 1975; Daan et al., 1996; Wolf & Schmid-Hempel, 1989]. We
      sought associations between longevity and individual variations in energy
      metabolism in a cohort of outbred mice. We found a positive association between
      metabolic intensity (kJ daily food assimilation expressed as g/body mass) and
      lifespan, but no relationships of lifespan to body mass, fat mass or lean body
      mass. Mice in the upper quartile of metabolic intensities had greater resting
      oxygen consumption by 17% and lived 36% longer than mice in the lowest intensity
      quartile. Mitochondria isolated from the skeletal muscle of mice in the upper
      quartile had higher proton conductance than mitochondria from mice from the
      lowest quartile. The higher conductance was caused by higher levels of endogenous
      activators of proton leak through the adenine nucleotide translocase and
      uncoupling protein-3. Individuals with high metabolism were therefore more
      uncoupled, had greater resting and total daily energy expenditures and survived
      longest - supporting the 'uncoupling to survive' hypothesis.

PMID- 15153177
TI  - The relative lengths of individual telomeres are defined in the zygote and
      strictly maintained during life.
AB  - Previous studies have indicated that average telomere length is partly inherited
      (Slagboom et al., 1994; Rufer et al., 1999) and that there is an inherited
      telomere pattern in each cell (Graakjaer et al., 2003); (Londono-Vallejo et al.,
      2001). In this study, we quantify the importance of the initially inherited
      telomere lengths within cells, in relation to other factors that influence
      telomere length during life. We have estimated the inheritance by measuring
      telomere length in monozygotic (MZ) twins using Q-FISH with a telomere specific
      peptide nucleic acid (PNA)-probe. Homologous chromosomes were identified using
      subtelomeric polymorphic markers. We found that identical homologous telomeres
      from two aged MZ twins show significantly less differences in relative telomere
      length than when comparing the two homologues within one individual. This result
      means that towards the end of life, individual telomeres retain the
      characteristic relative length they had at the outset of life and that any length
      alteration during the lifespan impacts equally on genetically identical
      homologues. As the result applies across independent individuals, we conclude
      that, at least in lymphocytes, epigenetic/environmental effects on relative
      telomere length are relatively minor during life.

PMID- 15153178
TI  - Telomere shortening in human fibroblasts is not dependent on the size of the
      telomeric-3'-overhang.
AB  - Telomeres shorten in human somatic cells with each round of DNA replication, and
      this shortening is thought to ultimately trigger replicative senescence. Telomere
      shortening is caused partly by the inability of semiconservative DNA replication
      to copy a linear strand of DNA to its very end. Post-replicative processing of
      telomeric ends, producing single-stranded G-rich 3' overhangs, has also been
      suggested to contribute to telomere shortening. This suggestion implies that a
      positive correlation should exist between the length of 3' overhangs and the rate
      of telomere shortening. We confirmed shortening of overhangs as human lung (MRC5)
      and foreskin (BJ) fibroblasts approach senescence by measuring overhang length
      using in-gel hybridization. However, a large study of fibroblast strains from 21
      donors maintained under conditions which lead to two orders of magnitude of
      variation in telomere shortening rate failed to show any correlation between
      telomere overhang length and shortening rate, suggesting that overhang length is
      neither a cause nor a correlate of telomere shortening.

PMID- 15153179
TI  - Microarray analysis of gene expression with age in individual nematodes.
AB  - We compare the aging of wild-type and long-lived C. elegans by gene expression
      profiling of individual nematodes. Using a custom cDNA array, we have
      characterized the gene expression of 4-5 individuals at 4 distinct ages
      throughout the adult lifespan of wild-type N2 nematodes, and at the same ages for
      individuals of the long-lived strain daf-2(e1370). Using statistical tools
      developed for microarray data analysis, we identify genes that differentiate
      aging N2 from aging daf-2, as well as classes of genes that change with age in a
      similar way in both genotypes. Our novel approach of studying individual
      nematodes provides practical advantages, since it obviates the use of mutants or
      drugs to block reproduction, as well as the use of stressful mass-culturing
      procedures, that have been required for previous microarray studies of C.
      elegans. In addition, this approach has the potential to uncover the molecular
      variability between individuals of a population, variation that is missed when
      studying pools of thousands of individuals.

PMID- 15153180
TI  - Demographic window to aging in the wild: constructing life tables and estimating
      survival functions from marked individuals of unknown age.
AB  - Summary We address the problem of establishing a survival schedule for wild
      populations. A demographic key identity is established, leading to a method
      whereby age-specific survival and mortality can be deduced from a marked cohort
      life table established for individuals that are randomly sampled at unknown age
      and marked, with subsequent recording of time-to-death. This identity permits the
      construction of life tables from data where the birth date of subjects is
      unknown. An analogous key identity is established for the continuous case in
      which the survival schedule of the wild population is related to the density of
      the survival distribution in the marked cohort. These identities are explored for
      both life tables and continuous lifetime data. For the continuous case, they are
      implemented with statistical methods using non-parametric density estimation
      methods to obtain flexible estimates for the unknown survival distribution of the
      wild population. The analytical model provided here serves as a starting point to
      develop more complex models for residual demography, i.e. models for estimating
      survival of wild populations in which age-at-entry is unknown and using remaining
      information in randomly encountered individuals. This is a first step towards a
      broad new concept of 'expressed demographic information content of marked or
      captured individuals'.

PMID- 15153181
TI  - Environment-dependent survival of Drosophila melanogaster: a quantitative genetic
      analysis.
AB  - Summary Survival under starvation conditions was investigated in relationship to
      survival when food was present because these traits could be linked by
      evolutionary history. Recombinant inbred lines derived from natural populations
      of Drosophila melanogaster were used to test genetic correlations and
      architecture of these survival traits. Sexes were genetically correlated within
      traits and there was significant correlation between survival traits. A number of
      quantitative trait loci (QTLs) were present for starvation survival and/or
      survival on food. In general, the QTL effects were consistent for sexes and
      environments. QTL effects were found on each major chromosome, but the major
      effects were largely localized on the second chromosome. Importantly, the 'four
      allele' progenitor of the recombinant inbred lines used in the present study
      allowed the sign and magnitude of effects to be assigned to linkage groups. One
      such linkage group on the second chromosome conferred starvation resistance and
      longevity, supporting the hypothesis of an association between starvation
      resistance and lifespan.

PMID- 15153182
TI  - Head-to-head debate between Richard Miller and Paul Hasty/Jan Vijg. Aging Cell
      Vol. 3, Issue 2 (2004).

PMID- 15153183
TI  - Biochemical and molecular responses to water stress in resurrection plants.
AB  - A small group of angiosperms, known as resurrection plants, can tolerate extreme
      dehydration. They survive in arid environments because they are able to
      dehydrate, remain quiescent during long periods of drought, and then resurrect
      upon rehydration. Dehydration induces the expression of a large number of
      transcripts in resurrection plants. Gene products with a putative protective
      function such as LEA proteins have been identified; they are expressed at high
      levels in the cytoplasm or in chloroplasts upon dehydration and/or ABA treatment
      of vegetative tissue. An increase in sugar concentration is usually observed at
      the onset of desiccation in vegetative tissue of resurrection plants. These
      sugars may be effective in osmotic adjustment or they may stabilize membrane
      structures and proteins. Regulatory genes such as a protein translation
      initiation factor, homeodomain-leucine zipper genes and a gene probably working
      as a regulatory RNA have been isolated and characterized. The knowledge of the
      biochemical and molecular responses that occur during the onset of drought may
      help to improve water stress tolerance in plants of agronomic importance.

PMID- 15153184
TI  - Applied environmental stresses to enhance the levels of polyphenolics in leaves
      of hawthorn plants.
AB  - In this investigation, two species of Crataegus (hawthorn) were chosen because
      their polyphenolic constituents have recently received greater attention for the
      treatment of patients with severe heart disease. One-year-old plants of hawthorn
      (Crataegus laevigata and C. monogyna) were subjected to water-deficit (continuous
      water deprivation), cold (4 degrees C), flooding (immersion of roots of plants in
      water) or herbivory (leaf removal) stress treatments (each of 10 days duration)
      in order to assess their effects on levels of polyphenolics, namely (-)
      epicatechin, catechin, chlorogenic acid, vitexin, vitexin-2"-O-rhamnoside,
      acetylvitexin-2"-O-rhamnoside, hyperoside, quercetin, and rutin in the leaves.
      The working hypothesis followed is that one or more of these stress treatment
      will elicit increases in the levels of these polyphenolics. Cold stress causes
      increases in levels of vitexin-2"-O-rhamnoside, acetylvitexin-2"-O-rhamnoside,
      hyperoside, and quercetin in both Crataegus species. Water-deficit stress
      increased the productivity of chlorogenic acid, catechin, and (-)-epicatechin in
      both hawthorn species. Flooding and herbivory caused no net increases, and in
      some cases, decreases in levels of polyphenolics. These studies indicate that
      either water-deficit stress or cold stress treatments, or a combination of the
      two, can be used to enhance the levels of desired polyphenolics in the leaves of
      these two hawthorn species in a photobioreactor system. These results may have
      significance for hawthorn in adapting to water-deficit or cold stress and are
      important considerations for the use of hawthorn in the treatment of heart
      disease in humans.

PMID- 15153185
TI  - Protein-level expression and localization of sucrose synthase in the sugarcane
      culm.
AB  - No comprehensive studies on the localization of sucrose synthase (SuSy, EC
      2.4.1.13) in sugarcane internodes have been reported. The expression and
      localization of SuSy in young (internode 3) to mature (internode 9) internodes of
      sugarcane (Saccharum spp. hybrids) var. N19 was investigated. Enzyme activity in
      the top and bottom, as well as the peripheral and core parts of the internodes
      suggested that SuSy is present ubiquitously but that levels can differ
      significantly in different parts of the internodes and with maturity. This was
      also confirmed by immunohistochemistry, which showed that both vascular and
      storage parenchyma tissues contain SuSy in young and mature internodes. The ratio
      of sucrose breakdown to synthesis activity increased approximately 12-fold from
      an average of 0.12 in internode three to 1.4 in internode nine. This indicates
      that different forms of SuSy are present in young and mature internodes, or that
      the ratios of different isoforms differ between young and mature internodes.
      Immunoblotting showed that at least one form of SuSy present in young tissue was
      absent, or present below detection limits, in mature culm tissue.

PMID- 15153186
TI  - Lipid-binding form is a key conformation to induce a programmed cell death
      initiated in tobacco BY-2 cells by a proteinaceous elicitor of cryptogein.
AB  - Cryptogein, a proteinaceous elicitor secreted by Phytophthora cryptogea, induces
      a remarkable hypersensitive cell death in tobacco cells. Two cryptogein mutants
      were analysed to characterize the induction mechanism of cell death; one was a
      newly synthesized mutant N93A whose 93rd Asn residue was changed to Ala, the
      other was K13V whose Lys at position 13 was replaced with Val. The effect of
      these mutations was evaluated in terms of extracellular alkalization, production
      of active oxygen species (AOS) and progression to death. The mutation N93A
      resulted in a reduction in activity to 71.0, 74.6 and 24.5% for original rates of
      extracellular alkalization, AOS production and cell death progression,
      respectively. In the case of the K13V mutation, these rates changed to 114, 3.38
      and 7.40%, respectively. The lipid-binding activities of the mutants were
      analysed using fluorogenic lipid of dehydroergosterol. The results for N93A and
      K13V were 38.3 and 3.40% compared with the wild type, respectively. These
      findings indicate that the lipid-binding form was the only conformation to induce
      the production of AOS and programmed cell death in plants.

PMID- 15153187
TI  - Carbon partitioning in leaves and tubers of transgenic potato plants with reduced
      activity of fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase.
AB  - The role of fructose-2,6-bisphosphate (Fru-2,6-P(2)) in regulation of carbon
      metabolism was investigated in transgenic potato plants (Solanum tuberosum L. cv
      Dianella) transformed with a vector containing a cDNA-sequence encoding fructose
      6-phosphate,2-kinase (F6P,2-K, EC 2.7.1.105)/fructose-2,6-bisphosphatase
      (F26BPase, EC 3.1.3.46) in sense or antisense direction behind a CaMV 35S
      promoter. The activity of F6P,2-K in leaves was reduced to 5% of wild-type (WT)
      activity, and the level of Fru-2,6-P(2) was reduced both in leaves (10% of the WT
      level) and in tubers (40% of the WT level). Analysis of photosynthetic (14)CO(2)
      metabolism, showed that in plant lines with reduced Fru-2,6-P(2) level the carbon
      partitioning in the leaves was changed in favour of sucrose biosynthesis, and the
      soluble sugars-to-starch labelling ratio was doubled. The levels of soluble
      sugars and hexose phosphates also increased in leaves of the transgenic plants.
      Most notably, the levels of hexoses were four- to six-fold increased in the
      transgenic plants. In tubers with reduced levels of Fru-2,6-P(2) only minor
      effects on carbohydrate levels were observed. Furthermore, carbon assimilation in
      tuber discs supplied with [U-(14)C]-sucrose showed only a moderate increase in
      labelling of hexoses and a decreased labelling of starch. Similar results were
      obtained using [U-(14)C]-glucose. No differences in growth of the transgenic
      lines and the WT were observed. Our data provide evidences that Fru-2,6-P(2) is
      an important factor in the regulation of photosynthetic carbon metabolism in
      potato leaves, whereas the direct influence of Fru-2,6-P(2) on tuber metabolism
      was limited.

PMID- 15153188
TI  - Cytokinin N-glucosylation inhibitors suppress deactivation of exogenous
      cytokinins in radish, but their effect on active endogenous cytokinins is
      counteracted by other regulatory mechanisms.
AB  - The prolongation of the effect of exogenous cytokinins by inhibition of their
      inactivation was studied in Raphanus sativus L. cv. Rampouch. As in radish the
      main way of cytokinin inactivation is their N-glucosylation, inhibitors of this
      pathway, papaverine, theophylline and olomoucine, as well as two olomoucine
      analogues, bohemine and roscovitine, were tested. The latter ones, which function
      as potent inhibitors of cyclin-dependent kinases, have also been found to
      effectively inhibit cytokinin N-glucosylation. Incubation (24 h) of de-rooted
      radish seedlings with inhibitors resulted in c. 50% decrease of the conversion of
      model cytokinins, [(3)H]dihydrozeatin and [(3)H]N(6)-benzyladenine, to the
      corresponding 7N-glucosides. Simultaneously the level of the non-metabolized
      cytokinin bases was elevated. The activity of cytokinin oxidase/dehydrogenase (EC
      1.5.99.12) was suppressed in a dose dependent manner. The concentration of
      physiologically active endogenous cytokinins was not increased significantly by
      inhibitor application. The inhibition of N-glucosylation was in the case of
      olomoucine, bohemine and roscovitine accompanied by the accumulation of
      physiologically nonactive cis-zeatin derivatives. The impact of inhibitors on the
      endogenous cytokinin pool seems to be balanced by the mechanisms involved in the
      maintenance of cytokinin homeostasis.

PMID- 15153189
TI  - Acid phosphatases from beet root (Beta vulgaris) plasma membranes.
AB  - Several acid phosphatases (EC 3.1.3.2) were found in beet root (Beta vulgaris L.)
      plasma membranes. Two of them were partially purified by an extraction of plasma
      membranes with octylglucoside and successive gel-filtration and anion-exchange
      chromatographies. With p-nitrophenyl-phosphate (pNPP) as substrate, most of the
      phosphatase activity was found in a fraction containing an 82-kDa protein. This
      phosphatase showed an optimum pH of 5.4 and was inhibited by Cu(2+), Zn(2+),
      molybdate or vanadate. The other phosphatase had a lower specific activity with
      pNPP, but was able to dephosphorylate phospho-myelin basic protein (phospho-MBP).
      This phosphatase presented two polypeptides with molecular masses of 36 and 65
      kDa and was 83% inhibited by 2 nM okadaic acid, which suggests it is a PP2A
      protein phosphatase. As the phosphatase activity was high in soluble (non
      membrane) fractions, the possibility that phosphatases in plasma membranes were
      soluble contaminants was assessed. Following the method of Berczi and Moller
      (Plant Physiol. 116:1029, 1998), it was found that about 45% of both acid and
      protein phosphatase activities could be due to soluble enzymes trapped inside
      membrane vesicles.

PMID- 15153190
TI  - Over-expression of ascorbate peroxidase in tobacco chloroplasts enhances the
      tolerance to salt stress and water deficit.
AB  - The role of APX (ascorbate peroxidase) in protection against oxidative stress was
      examined using transgenic tobacco plants. The full length cDNA, coding
      Arabidopsis thaliana L. APX fused downstream to the chloroplast transit sequence
      from A. thaliana glutathione reductase, was cloned into appropriate binary vector
      and mobilized into Agrobacterium tumefaciens C58C2. Leaf discs were infected with
      the Agrobacterium and cultured on medium supplied with kanamycin. The
      incorporation of the gene in tobacco genome was confirmed by Southern dot blot
      hybridization. Transgenic lines were generated, and the line Chl-APX5 shown to
      have 3.8-fold the level of APX activity in the wild-type plants. The isolated
      chloroplasts from this line showed higher APX activity. During early
      investigation, this line showed enhanced tolerance to the active oxygen
      generating paraquat and sodium sulphite. The first generation of this line, also,
      showed enhanced tolerance to salt, PEG and water stresses, as determined by net
      photosynthesis. The present data indicate that overproducing the cytosolic APX in
      tobacco chloroplasts reduces the toxicity of H(2)O(2).

PMID- 15153191
TI  - Reduction of dark chilling stress in N-fixing soybean by nitrate as indicated by
      chlorophyll a fluorescence kinetics.
AB  - Sub-optimal night temperatures below 15 degrees C (dark chilling) frequently
      reduce soybean [Glycine max (L.) Merrill] production. Nitrate application is
      known to alleviate some of the negative effects of low root zone temperatures,
      probably by counteracting the inhibition caused by decreased symbiotic nitrogen
      fixation (SNF). Under field conditions, however, dark chilling is frequently not
      accompanied by low root zone temperatures. The possibility that nitrate might
      increase dark-chilling tolerance under these conditions is still largely
      unexplored. In addition to quantifying vegetative development by means of the
      plastochron index, O-J-I-P (O-I(1)-I(2)-P) chlorophyll a fluorescence transients
      were recorded in soybean genotypes of contrasting chilling tolerance during and
      following exposure to dark chilling in the absence of low root zone temperatures.
      Plants, inoculated with the N(2)-fixing bacteria, Bradyrhizobium japonicum, were
      grown with and without nitrate supplementation. The recorded O-J-I-P chlorophyll
      a fluorescence transients were analysed by the so-called JIP-test which
      translates stress-induced alterations in these transients to changes in
      biophysical parameters that quantifies the energy flow through photosystem II
      (PSII). One of these parameters, the performance index (PI(ABS)), combines the
      three main functional steps (light energy absorption, excitation energy trapping,
      and conversion of excitation energy to electron transport) of photosynthetic
      activity by a PSII reaction centre complex into a single multiparametric
      expression. By using the PI(ABS) we could convincingly show that nitrate
      supplementation considerably enhances dark-chilling tolerance and recovery
      capacity of plants in the absence of low root zone temperatures. This was
      especially true for the chilling-sensitive genotype ('Java 29'), suggesting that
      the response of SNF to dark chilling might be an important factor contributing
      towards genotypic differences in chilling tolerance. Our results corroborated
      previous reports about the superior chilling tolerance of 'Maple Arrow', a
      chilling-tolerant genotype. The results obtained indicated that the PI(ABS) is a
      far more sensitive indicator of dark-chilling stress than the maximum quantum
      yield of primary photochemistry (F(V)/F(M)).

PMID- 15153192
TI  - Senescence and hyperspectral reflectance of cotton leaves exposed to ultraviolet
      B radiation and carbon dioxide.
AB  - The objectives of this study were to determine the effects of UV-B radiation and
      atmospheric carbon dioxide concentrations ([CO(2)]) on leaf senescence of cotton
      by measuring leaf photosynthesis and chlorophyll content and to identify changes
      in leaf hyperspectral reflectance occurring due to senescence and UV-B radiation.
      Plants were grown in controlled-environment growth chambers at two [CO(2)] (360
      and 720 micro mol mol(-1)) and three levels of UV-B radiation (0, 7.7 and 15.1 kJ
      m(-2) day(-1)). Photosynthesis, chlorophyll, carotenoids and phenolic compounds
      along with leaf hyperspectral reflectance were measured on three leaves aged 12,
      21 and 30 days in each of the treatments. No interaction was detected between
      [CO(2)] and UV-B for any of the measured parameters. Significant interactions
      were observed between UV-B and leaf age for photosynthesis and stomatal
      conductance. Elevated [CO(2)] enhanced leaf photosynthesis by 32%. On exposure to
      0, 7.7 and 15.1 kJ of UV-B, the photosynthetic rates of 30-day-old leaves
      compared with 12-day-old leaves were reduced by 52, 76 and 86%, respectively.
      Chlorophyll pigments were not affected by leaf age at UV-B radiation of 0 and 7.7
      kJ, but UV-B of 15.1 kJ reduced the chlorophylls by 20, 60 and 80% in 12, 21 and
      30-day-old leaves, respectively. The hyperspectral reflectance between 726 and
      1142 nm showed interaction for UV-B radiation and leaf age. In cotton, leaf
      photosynthesis can be used as an indicator of leaf senescence, as it is more
      sensitive than photosynthetic pigments on exposure to UV-B radiation. This study
      revealed that, cotton leaves senesced early on exposure to UV-B radiation as
      indicated by leaf photosynthesis, and leaf hyperspectral reflectance can be used
      to detect changes caused by UV-B and leaf ageing.

PMID- 15153193
TI  - Promotion of 5-aminolevulinic acid on photosynthesis of melon (Cucumis melo)
      seedlings under low light and chilling stress conditions.
AB  - When melon seedlings (Cucumis melo L. Ximiya No. 1) were cultured in a growth
      chamber with about 150 micro mol m(-2) s(-1) photon flux density, the leaf
      photosynthetic ability reduced dramatically as leaf position decreased from the
      top. The application of 5-aminolevulinic acid (ALA) solutions significantly
      increased the net photosynthetic rate (P(n)) as well as apparent quantum yield
      (AQY), carboxylation efficiency (CE) and stomata conductance (G(s)). After
      irrigation with 10 ml of ALA solution (10 mg l(-1) or 100 mg l(-1)) per container
      filled with approximately 250 g clean sand for 3 days, the leaf P(n) was about 40
      200% higher than that of controls, and AQY, CE and G(s) increased 21-271%, 55
      210% and 60-335%, respectively. Furthermore, ALA treatments increased leaf
      chlorophyll content and soluble sugar levels, as well as the rate of dark
      respiration, but decreased the rate of respiration under light. On the other
      hand, after melon seedlings that had been cultured in the chamber suffered
      chilling at 8 degrees C for 4 h and then recovered at 25-30 degrees C for 2 and
      20 h, the P(n) of the water-irrigated plants was only 12-18% and 37-47%,
      respectively, compared with the initial P(n) before chilling treatment. If the
      seedlings underwent the same treatment but with ALA (10 mg l(-1)), the respective
      P(n) was 22-38% and 76-101%, compared with that of the control before chilling
      stress. If chilling was prolonged for 6 h, the ALA-pre-treated plants only showed
      a few symptoms in the leaf margins whereas all water-irrigated plants died, which
      suggested that ALA presumably promoted chilling tolerance of the plants under low
      light.

PMID- 15153194
TI  - Effects of NaCl on water relations and cell wall elasticity and composition of
      red-osier dogwood (Cornus stolonifera) seedlings.
AB  - Red-osier dogwood (Cornus stolonifera Michx, Syn. Cornus sericea), a species
      relatively well adapted to moderately saline conditions compared with other
      boreal species, was used to test the effects of NaCl on plant water relations,
      cell wall elasticity, and cell wall composition of seedlings. Three month-old
      seedlings were treated hydroponically with 0, 25, and 50 mm NaCl for 21 days. The
      osmotic potential at full turgor, osmotic potential at turgor loss, pressure
      potential at full turgor, and relative water content at turgor loss of red-osier
      dogwood shoot tissue were not significantly affected by the NaCl treatments. Cell
      wall elasticity of the shoot tissues did not change following NaCl treatments,
      suggesting that elastic adjustment did not play a role in the adaptation
      mechanism. Hemicellulose content of the cell wall increased in salt treated
      seedlings. The primary sugar found in the cell wall hemicellulose fraction was
      xylose. In the pectin fraction arabinose and galacturonic acid were the main
      sugars. Sodium chloride stress did not alter the sugar composition of the
      hemicellulose fraction; however, NaCl did increase the amount of rhamnose in the
      pectin fraction. The results of this study suggest that at moderate salinity red
      osier dogwood does not make any osmotic or elastic adjustments in the shoot
      tissue, but some changes in the cell wall composition do occur. These changes
      could contribute to the decrease in growth recorded in red-osier dogwood during
      NaCl stress.

PMID- 15153195
TI  - Processes contributing to photoprotection of grapevine leaves illuminated at low
      temperature.
AB  - Photoinactivation of photosystem II (PSII) and energy dissipation at low leaf
      temperatures were investigated in leaves of glasshouse-grown grapevine (Vitis
      vinifera L. cv. Riesling). At low temperatures (< 15 degrees C), photosynthetic
      rates of CO(2) assimilation were reduced. However, despite a significant increase
      in the amount of light excessive to that required by photosynthesis, grapevine
      leaves maintained high intrinsic quantum efficiencies of PSII (F(v)/F(m)) and
      were highly resistant to photoinactivation compared to other species. Non
      photochemical energy dissipation involving xanthophylls and fast D1 repair were
      the main protective processes reducing the 'gross' rate of photoinactivation and
      the 'net' rate of photoinactivation, respectively. We developed an improved
      method of energy dissipation analysis that revealed up to 75% of absorbed light
      is dissipated thermally via pH- and xanthophyll-mediated non-photochemical
      quenching at low temperatures (5-15 degrees C) and moderate (800 micro mol quanta
      m(-2) s(-1)) light. Up to 20% of the energy flux contributing to electron
      transport was dissipated via photorespiration when taking into account
      temperature-dependent mesophyll conductance; however, this flux used in
      photorespiration was only a relatively small amount of the total absorbed light
      energy. Photoreduction of O(2) at photosystem I (PSI) and subsequent superoxide
      detoxification (water-water cycle) was more sensitive to inhibition by low
      temperature than photorespiration. Therefore the water-water cycle represents a
      negligibly small energy sink below 15 degrees C, irrespective of mesophyll
      conductance.

PMID- 15153196
TI  - Isolation of a novel barley cDNA encoding a nuclear protein involved in stress
      response and leaf senescence.
AB  - In order to isolate genes involved in the early acclimation of winter barley
      (Hordeum vulgare L. cv. Trixi) to a combined cold and light stress of 2 degrees C
      and 600 micromol m(-2) s(-1) restriction fragment differential display-polymerase
      chain reaction was performed. Impact of the cold-treatment on the leaves was
      characterized by measuring chlorophyll content and photosystem II efficiency. By
      this approach several cDNAs of genes that quickly and transiently up-regulated
      during early stages of the stress were identified. One of these genes (HvFP1)
      includes sequence motifs representing a heavy metal associated domain (HMA),
      nuclear localization signals (NLS) and a farnesylation motif. This gene is also
      induced at drought stress, during leaf senescence and after exposure to abscisic
      acid. Analysis of its spatial expression patterns in barley plants either grown
      at 21 or 2 degrees C showed that in contrast to the situation in leaves
      transcript level of this gene is high not only in cold-treated plants but also in
      controls kept at 21 degrees C in plant compartments enriched in meristematic
      tissues. The nuclear localization of the protein was confirmed by confocal laser
      scanning microscopy of epidermal onion cells after particle bombardment with
      chimeric HVFP1-GFP constructs. Using a construct with a modified farnesylation
      motif yielded a different pattern of nuclear distribution of the chimeric
      protein.

PMID- 15153197
TI  - Role of basipetal auxin transport and lateral auxin movement in rooting and
      growth of etiolated lupin hypocotyls.
AB  - The involvement of polar auxin transport (PAT) on the growth of light-grown
      seedlings and rooting is generally accepted, while the role of auxin and PAT on
      the growth of dark-grown seedlings is subject to controversy. To further
      investigate this question, we have firstly studied the influence of NPA, a known
      inhibitor of PAT, on the rooting and growth of etiolated Lupinus albus
      hypocotyls. Rooting was inhibited when the basal ends of de-rooted seedlings were
      immersed in 100 micro m NPA but was partially restored after immersion in NPA +
      auxin. However, NPA applied to de-rooted seedlings or the roots of intact
      seedlings did not inhibit hypocotyl growth. It was taken up and distributed along
      the organ, and actually inhibited the basipetal transport of ((3)H)-IAA applied
      to isolated hypocotyl sections. Since the apex is the presumed auxin source for
      hypocotyl growth and rooting, and the epidermis is considered the limiting factor
      in auxin-induced growth, the basipetal and lateral auxin movement (LAM) after
      application of ((3)H)-IAA to decapitated seedlings were studied, in an attempt to
      evaluate the role of PAT and LAM in the provision of auxin to competent cells for
      growth and rooting. Local application of ((3)H)-IAA to the stele led to the
      basipetal transport of auxin in this tissue, but the process was drastically
      reduced when roots were immersed in NPA since no radioactivity was detected below
      the apical elongation region of the hypocotyl. LAM from the stele to the cortex
      and the epidermis occurred during basipetal transport, since radioactivity in
      these tissues increased as transport time progressed. Radioactivity on a per FW
      basis in the epidermis was 2-4 times higher than in the cortex, which suggests
      that epidermal cells acted as a sink for LAM. NPA did not inhibit LAM along the
      elongation region. These results suggest that while PAT was essential for
      rooting, LAM from the PAT pathway to the auxin-sensitive epidermal cells could
      play a key role in supplying auxin for hypocotyl elongation in etiolated lupin
      seedlings.

PMID- 15153198
TI  - Bud endophytes of Scots pine produce adenine derivatives and other compounds that
      affect morphology and mitigate browning of callus cultures.
AB  - Endophytes are found in meristematic bud tissues of Scots pine (Pinus sylvestris
      L.) especially prior to growth, which would suggest their involvement in growth
      of the bud. To test this hypothesis, production of phytohormones by two bacterial
      (Methylobacterium extorquens, Pseudomonas synxantha) and one fungal endophyte
      (Rhodotorula minuta) was studied by mass spectrometry. The most common
      gibberellins, auxins, or cytokinins were not detected in the fractions studied.
      Instead, M. extorquens and R. minuta produced adenine derivatives that may be
      used as precursors in cytokinin biosynthesis. A plant tissue culture medium was
      conditioned with the endophytes, and pine tissue cultures were started on the
      media. Tetracycline inhibited callus production, which was restored on the
      endophyte-conditioned media. In addition, conditioning mitigated browning of the
      Scots pine explants. However, a decrease in tissue size was observed on the
      endophyte-conditioned media. Addition of adenosine monophosphate in the plant
      culture medium restored callus production and increased growth of the tissues,
      but had no effect on browning. Therefore, production of adenine ribosides by
      endophytes may play some role in the morphological effect observed in the pine
      tissues.

PMID- 15153199
TI  - Role of abscisic acid in perianth senescence of daffodil (Narcissus
      pseudonarcissus"Dutch Master").
AB  - Daffodil (Narcissus pseudonarcissus L. 'Dutch Master') flowers detached at the
      base of their ovaries and held with their cut ends in 10-100 microM abscisic acid
      (ABA) senesced prematurely. Symptoms of the ABA treatment included water-soaking
      of the tepals and early collapse of the corona. No water-soaking was seen in
      tepals of flowers held in water. Instead, the tepals of these flowers dried. The
      ABA content increased in tepals of the potted flowers as they senesced. The rise
      in tepal ABA content coincided with the appearance of visual signs of senescence.
      When the flowers were cut and placed in water, a treatment that accelerated their
      senescence, the increase in ABA occurred earlier. Exogenously applied ABA
      enhanced the premature accumulation of senescence-associated transcripts in the
      tepals. Their ABA-mediated induction was not prevented when the flowers were pre
      treated with 1-methylcyclopropene, an inhibitor of ethylene action, indicating
      that ABA induced the transcripts independently of ethylene. The transcripts
      accumulated in opened control flowers before the rise in endogenous ABA. Attempts
      to extend floral longevity by using putative inhibitors of ABA biosynthesis
      [tungstate, fluridone (applied as Sonar((R))) and 1,1-dimethyl-4
      (phenylsulphonyl)semicarbazide (DPSS)] were unsuccessful. However, inclusion of
      100 microM gibberellic acid (GA(3)) in the vase solution reduced the senescence
      inducing effects of 50 microM ABA suggesting a possible mechanism for in-vivo
      control of senescence.

PMID- 15153200
TI  - Photosystem II inhibition by moderate light under low temperature in intact
      leaves of chilling-sensitive and -tolerant plants.
AB  - Photosystem II (PSII) activity was examsined in leaves of chilling-sensitive
      cucumber (Cucumis sativus L.), tomato (Lycopersicum esculentum L.), and maize
      (Zea mays L.), and in chilling-tolerant barley (Hordeum vulgare L.) illuminated
      with moderate white light (300 micro mol m(-2) s(-1)) at 4 degrees C using
      chlorophyll a fluorescence measurements. PSII activity was inhibited in leaves of
      all the four plants as suggested by the decline in F(v)/F(m), 1/F(o) - 1/F(m),
      and F(v)/F(o) values. The changes in initial fluorescence level (F(o)),
      F(v)/F(m), 1/F(o) - /1/F(m), and F(v)/F(o) ratios indicate a stronger PSII
      inhibition in cucumber, maize and tomato plants. The kinetics of chlorophyll a
      fluorescence rise showed complex changes in the magnitudes and rise of O-J, J-I,
      and I-P phases caused by photoinhibition. The selective suppression of the J-I
      phase of fluorescence rise kinetics provides evidence for weakened electron
      donation from the oxidizing side, whereas the accumulation of reduced Q(A)
      suggests damage to the acceptor side of PSII. These findings imply that the
      process of chilling-induced photoinhibition involves damage to more than one site
      in the PSII complexes. Furthermore, comparative analyses of the decline in
      F(v)/F(o) and photooxidation of P700 explicitly show that the extent of
      photoinhibitory damage to PSII and photosystem I is similar in leaves of cucumber
      plants grown at a low irradiance level.

PMID- 15153201
TI  - The constant proportion of grana and stroma lamellae in plant chloroplasts.
AB  - The relative proportion of stroma lamellae and grana end membranes was determined
      from electron micrographs of 58 chloroplasts from 21 different plant species. The
      percentage of grana end membranes varied between 1 and 21% of the total thylakoid
      membrane indicating a large variation in the size of grana stacks. By contrast
      the stroma lamellae account for 20.3 +/- 2.5 (sd)% of the total thylakoid
      membrane. A plot of percentage stroma lamellae against percentage of grana end
      membranes fits a straight line with a slope of zero showing that the proportion
      of stroma lamellae is independent of the size of the grana stacks. That stroma
      lamellae account for about 20% of the thylakoid membrane is in agreement with
      fragmentation and separation analysis (Gadjieva et al. Biochim. Biophys. Acta
      144: 92-100, 1999). Chloroplasts from spinach, grown under high or low light,
      were fragmented by sonication and separated by countercurrent distribution into
      two vesicle populations originating from grana and stroma lamellae plus end
      membranes, respectively. The separation diagrams were very similar lending
      independent support for the notion that the proportion of stroma lamellae is
      constant. The results are discussed in relation to the composition and function
      of the chloroplast in plants grown under different environmental conditions, and
      in relation to a recent quantitative model for the thylakoid (Albertsson, Trends
      Plant Sci. 6: 349-354, 2001).

PMID- 15153202
TI  - Propofol infusion in children: when does an anesthetic tool become an intensive
      care liability?

PMID- 15153203
TI  - Sedation and neuromuscular blockade in paediatric intensive care; practice in the
      United Kingdom and North America.

PMID- 15153204
TI  - Diclofenac and metabolite pharmacokinetics in children.
AB  - BACKGROUND: Data concerning metabolism of diclofenac in children are limited to
      intravenous and enteric coated oral formulations. There are no data examining
      diclofenac or its hydroxyl metabolite pharmacokinetics after rectal
      administration in children. METHODS: Infants (n = 26) undergoing tonsillectomy
      were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository
      formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'
      hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure
      and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to
      hydroxyl metabolites were estimated using nonlinear mixed effects models. A
      single compartment, first order absorption and first order elimination model was
      used to describe diclofenac pharmacokinetics. Published data from 11 children
      given enteric-coated diclofenac tablets were used to assess relative
      bioavailability. RESULTS: Mean (sd) age and weight of the patients were 4.5 (1.5)
      years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV)
      and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively,
      standardized to a 70 kg person using allometric '1/4 power' models. Clearance by
      other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of
      hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of
      distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0)
      and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life
      of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of
      formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution,
      absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%,
      respectively. The relative bioavailability of the suppository compared with an
      enteric-coated tablet was 1.26. CONCLUSION: The formation clearance of the active
      metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1)
      70 kg(-1)). The rectum is a suitable route for administration of diclofenac in
      children 2-8 year of age and was associated with a higher relative bioavailabilty
      than enteric-coated tablets and an earlier maximum concentration (50 vs. 108
      min). This pharmacokinetic profile renders diclofenac suppository a suitable
      formulation for short duration surgery.

PMID- 15153205
TI  - Assessment of tracheal intubating conditions in children using remifentanil and
      propofol without muscle relaxant.
AB  - BACKGROUND: Tracheal intubation in children can be achieved by deep inhalational
      anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium
      being widely used despite several side-effects. Studies have shown that oral
      intubation can be facilitated safely and effectively in children after induction
      of anaesthesia with propofol and alfentanil without a muscle relaxant.
      Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is
      20-30 times more potent than alfentanil. This clinical study was designed to
      assess whether combination of propofol and remifentanil could be used without a
      muscle relaxant to facilitate tracheal intubation in children. METHODS: Forty
      children (5-10 years) admitted for adenotonsillectomy were randomly allocated to
      one of two groups to receive remifentanil 2 microg.kg(-1) (Gp I) or remifentanil
      3 microg.kg(-1) (Gp II) before the induction of anaesthesia with i.v. propofol 3
      mg.kg(-1). No neuromuscular blocking agent was administered. Intubating
      conditions were assessed using a four-point scoring system based on ease of
      laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and
      limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured
      noninvasively before induction of anaesthesia to 5 min after intubation (seven
      time points). RESULTS: Tracheal intubation was successful in all patients without
      requiring neuromuscular blocking agent. Intubating conditions were clinically
      acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients
      (90%) in Gp II (P < 0.05). MAP and HR decreased in both groups after induction of
      anaesthesia (P < 0.01). Both HR and MAP were significantly lower in Gp II
      compared with Gp I after tracheal intubation (P < 0.01). No patient in the
      present study developed bradycardia or hypotension. CONCLUSIONS: We conclude that
      remifentanil (3 microg.kg(-1)), administered before propofol (3 mg.kg(-1))
      provides acceptable tracheal intubating conditions in children, and completely
      inhibited the increase in HR and MAP associated with intubation.

PMID- 15153206
TI  - A comparison between single- and double-breath vital capacity inhalation
      induction with 8% sevoflurane in children.
AB  - BACKGROUND: This study was conducted to determine if a double-breath (DB) vital
      capacity (VC) rapid inhalation induction using immediate high-inspired
      concentration of sevoflurane is as well tolerated as a single-breath (SB)
      technique and if it results in a shorter induction time. METHODS: A total of 104
      children, ASA I-II, 6 year and above, undergoing elective surgery were randomly
      assigned to two groups: SB VC inhalation induction or DB VC inhalation induction
      with 8% sevoflurane in 66% nitrous oxide. The induction time, complications
      (cough, laryngospasm, breath-hold, movement, salivation) and level of
      satisfaction were documented. RESULTS: Induction was significantly faster in the
      DB group (41 +/- 9 s) compared with the SB group (50 +/- 14 s). DB inhalation
      induction was associated with fewer complications (15.4%) than the SB technique
      (50%). CONCLUSIONS: Double-breath VC inhalation induction with 8% sevoflurane is
      as well tolerated as a SB technique and results in a faster onset of anaesthesia.

PMID- 15153207
TI  - Dosage scheme for propofol in children under 3 years of age.
AB  - BACKGROUND: Propofol is a well-known drug for adults for total intravenous
      anaesthesia. Since 1999, the use of propofol has been approved for children less
      than 3 years of age. However, a suitable dosage scheme for these age groups was
      not available. The purpose of this study was to describe our clinical experience
      with the use of a new dosage scheme for propofol in patients under 3 years of
      age, based on experimental data and known pharmacological principles in children.
      METHODS: A pilot study of 50 patients undergoing TIVA was performed to adapt the
      existing adult dosage scheme to the requirements of the younger population. Total
      number and time of administration of boluses and time to awakening were
      registered and used as criteria to adjust the dosage scheme. The subsequent
      dosage scheme was then evaluated in 2271 children undergoing anaesthesia for
      various procedures. Usual anaesthetic parameters were measured to monitor the
      safety of the patient: ECG, O2 saturation, respiratory frequency and blood
      pressure. Most of the patients were mechanically ventilated; only 15% were
      breathing spontaneously. RESULTS: Overall, few side effects were recorded
      [bradycardia (12%), blood pressure fall (8%), desaturation (1%)], which were
      easily countered by routine measures. CONCLUSIONS: This dosage scheme provides
      safe and smooth anaesthesia in children less than 3 years of age and is therefore
      a useful tool for a TIVA technique in small children.

PMID- 15153209
TI  - Anaesthesia considerations for cardiac MRI in infants and small children.
AB  - BACKGROUND: General anaesthesia is frequently necessary in infants and small
      children undergoing cardiac magnetic resonance imaging (MRI), because of the
      imaging techniques, MRI environment and potential need for breath-holding to
      facilitate imaging. Anaesthetizing paediatric patients with congenital heart
      disease (CHD) for cardiac MRI poses many challenges for the anaesthetist and this
      report reviews our experience. METHODS: We retrospectively reviewed the
      anaesthesia and MRI records of all patients who had undergone cardiac MRI between
      January 2000 and October 2002. RESULTS: A total of 250 children with cardiac
      disease underwent general anaesthesia for cardiac MRI. ASA classification
      included class I, 2%; class II; 26%; class III, 60% and class IV, 12%. A total of
      168 patients (67%) had undergone previous cardiac surgery, 182 patients (94%)
      were discharged the same day and 48 patients (19.2%) had cyanotic cardiac defects
      (SpO2 between 55 and 85%). No scans were interrupted because of low oxygen
      saturation during breath-hold or haemodynamic instability. No patient was
      admitted to the hospital from complications related to general anaesthesia, but
      one inhouse patient from the cardiology ward was admitted to the cardiac
      intensive care unit (CICU) after the MRI because of cyanosis and low cardiac
      output. Seven patients from the CICU were on inotropic infusions when they
      underwent the MRI procedure and two others needed inotropic support after
      induction of anaesthesia. Five patients had a brief episode of hypotension during
      the MRI and responded quickly to interventions. CONCLUSION: Our experience
      demonstrates that general anaesthesia for cardiac MRI can be provided safely in
      infants and small children with CHD, despite the complexity and pathophysiology
      of many defects, the frequent breath-holding for image acquisitions and the MRI
      environment.

PMID- 15153208
TI  - Comparison of ropivacaine with bupivacaine and lidocaine for ilioinguinal block
      after ambulatory inguinal hernia repair in children.
AB  - BACKGROUND: We have compared ropivacaine with bupivacaine and lidocaine for
      ilioinguinal block in thirty children undergoing ambulatory inguinal hernia
      repair. METHODS: Patients were assigned randomly to receive 0.5 ml.kg(-1) of 0.2%
      ropivacaine (Group R, n = 10), 0.25% bupivacaine (Group B, n = 10) or 1%
      lidocaine (Group L, n = 10). The patients' parents, who were not informed of the
      type of local anaesthetic employed, evaluated the postoperative pain at 2 h and 6
      h after operation using the Wong-Baker FACES Pain Rating Scale. RESULTS: There
      was a significant difference in the face scale score between Group R and Group L,
      and Group B and Group L. There was no difference in the face scale score between
      Group R and Group B. There were no complications or clinical evidence of local
      anaesthetic toxicity. CONCLUSIONS: We have confirmed that bupivacaine and
      ropivacaine are more effective than lidocaine in the prevention of postoperative
      pain after children's inguinal hernia repair. We suggest that ropivacaine 0.2% is
      an alternative to bupivacaine 0.25% for ilioinguinal block in ambulatory
      paediatric surgery.

PMID- 15153210
TI  - Oral ketamine premedication can prevent emergence agitation in children after
      desflurane anaesthesia.
AB  - BACKGROUND: The purpose of the present study was to determine whether oral
      ketamine premedication affected the incidence of emergence agitation in children.
      METHODS: Thirty minutes before induction of anaesthesia, 80 children who were
      undergoing adenotonsillectomy with or without bilateral myringotomy and insertion
      of tubes received either ketamine 6 mg.kg(-1) per oral in group K or sour cherry
      juice alone in group C. Anaesthesia was maintained with desflurane. Emergence and
      recovery times were recorded. Tramadol was used for postoperative analgesia.
      Fentanyl (1 microg.kg(-1)) was administered for the treatment of emergence
      agitation or severe pain that still continued after tramadol administration.
      Postoperative behaviour was evaluated using a 5-point agitation scale. RESULTS:
      The incidence of emergence agitation was 56% in group C, and 18% in group K (P =
      0.001). There was no significant difference with respect to emergence times
      except from time to eye opening that was significantly longer in group K (P <
      0.0001). CONCLUSION: Oral ketamine premedication reduced the incidence of
      postanaesthesia emergence agitation in children without delaying recovery.

PMID- 15153211
TI  - Analgesic effect of clonidine added to bupivacaine 0.125% in paediatric caudal
      blockade.
AB  - BACKGROUND: Caudals are a common method of providing pain relief in children
      undergoing surgery. Clonidine, an alpha(2) agonist, exhibits significant
      analgesic properties. The current investigation sought to determine whether
      caudal clonidine added to caudal bupivacaine would decrease pain in paediatric
      patients undergoing surgery. METHODS: Thirty-six children undergoing elective
      surgery were studied. Following anaesthetic induction, a caudal was placed (1
      mg.kg(-1) bupivacaine 0.125%) with an equal volume of either clonidine (2
      microg.kg(-1)) or saline. Perioperative analgesic requirements in the
      postanaesthesia care unit (PACU) and at home following hospital discharge, and
      parental pain scores were evaluated. RESULTS: There were no significant
      demographic, haemodynamic, or pain score differences between the groups. There
      was no difference in analgesic duration between groups. There were significantly
      more children who vomited during the first 24 postoperative hours in the
      clonidine group than in the saline group (eight in clonidine, two in saline; P <
      0.05). CONCLUSION: We do not recommend adding clonidine (2 microg.kg(-1)) to a
      bupivacaine (0.125%) caudal block in children undergoing surgery.

PMID- 15153213
TI  - Manikin training for neonatal resuscitation with the laryngeal mask airway.
AB  - BACKGROUND: We describe our experience of brief (< or =15 min) manikin-only
      training with the laryngeal mask airway (LMA) for neonatal resuscitation in 80
      health care workers. METHODS: Prior to training, 31% had not heard of the LMA,
      57% did not know the LMA could be used for neonatal resuscitation and 88% thought
      it was a disposable device. RESULTS: The mean (SD) range time to insert the LMA
      after training was 5 (2, 5-16) s and there were no failed insertions. The
      preferred technique for neonatal resuscitation, before vs after training, changed
      from 72 to 14% for the face mask (P < 0.00001), from 6 to 80% for the LMA (P <
      0.00001), from 5 to 0% for laryngoscope-guided tracheal intubation (P = 0.04) and
      from 16 to 5% for unknown (P = 0.02). All considered that training was adequate
      and the LMA should be available on neonatal resuscitation carts. Confidence in
      using the LMA increased from 8 to 97% (P < 0.0001). CONCLUSIONS: We conclude that
      LMA insertion success rates are high and confidence increases after brief manikin
      only training.

PMID- 15153212
TI  - Use of intravenous ketorolac in the neonate and premature babies.
AB  - BACKGROUND: Ketorolac is a powerful nonsteroidal anti-inflammatory drug widely
      used for pain control in children and adults. The aim of this study was to
      evaluate its safety and analgesic efficacy in the neonate. METHODS: Ketorolac was
      used in a group of 18 spontaneously breathing neonates presenting with chronic
      lung disease, for the control of postsurgical pain and pain from invasive
      procedures. Pain scores (Neonatal Infant Pain Scale) were assessed before and
      after i.v. administration of 1 mg.kg(-1) of ketorolac. RESULTS: Total pain
      control was achieved in 94.4% of the neonates. None of the neonates had
      haematological, renal or hepatic changes prior to treatment, and these
      complications did not occur after treatment. No neonate had systemic haemorrhage
      or bleeding from injection and blood withdrawal sites. CONCLUSIONS: Ketorolac
      could represent an efficacious analgesic alternative to opioids, particularly in
      neonates. It would avoid the side-effects associated with opioid analgesics,
      especially respiratory depression.

PMID- 15153214
TI  - Delayed rises in serum S100B levels and adverse neurological outcome in infants
      and children undergoing cardiopulmonary bypass.
AB  - BACKGROUND: The protein S100B is a marker of brain injury. Early after
      cardiopulmonary bypass (CPB), serum S100B levels are artefactually high. We
      investigated whether delayed (48 h) rise in S100B levels may have a role in
      detecting brain injury after CPB. METHODS: Data from 43 children were analysed in
      this study. Samples were collected at preincision and 30 min, 24 and 48 h
      postbypass and then analysed by using a commercially available radioimmunoassay
      (Sangtec100). Charts were reviewed at 3-5 months for evidence of neurological
      injury. RESULTS: S100B levels were high preoperatively in neonates and
      universally high immediately postbypass. In 36 children, samples were available
      for all time points. Compared with preoperative levels, rises occurred at both 24
      and 48 h in three patients, only at 24 h in four patients and only at 48 h in
      three patients. Two patients had evidence of neurological injury. A rise at 48 h
      was associated with neurological injury (odds ratio 33.9, P < 0.03, 95% CI 1.39
      827). There was no association between neurological injury and S100B levels at 24
      h. Both the patients with neurological injury had rises at 48 h that were
      significantly higher than patients with rises at 48 h without injury.
      CONCLUSIONS: The results of this study suggest that monitoring S100B levels in
      the late postoperative period may still have a role in detecting neurological
      injury after cardiac surgery in children. Consistent with previous observations,
      S100B is high preoperatively in neonates and early postbypass in all patients.

PMID- 15153215
TI  - Current patterns of propofol use in PICU in the United Kingdom and North America.
AB  - BACKGROUND: Our aim was to investigate the current patterns of propofol use in
      pediatric intensive care units (PICUs) in the UK and North America. METHODS: An
      electronic questionnaire was sent to all PICUs in the UK and those units offering
      PICU training fellowships in the USA and Canada. RESULTS: We received responses
      from 15 UK units (75%) and 33 units in North America (52%). Of units who
      responded, 47% of UK units used propofol for ongoing sedation, compared with 61%
      of North American units. Units tended to use propofol in defined clinical
      circumstances, in limited doses, in older children and for relatively short
      periods. Propofol was used for sedation during procedures in 100% of units
      although 35% of UK units said that they would use it less frequently in this
      setting than in the past. Only 18% of North American Units reported that they
      would be less likely to use propofol for procedures than in the past.
      CONCLUSIONS: Despite clear guidance from the UK Committee on Safety of Medicines,
      propofol was still used for ongoing sedation in 47% of UK PICUs responding to our
      questionnaire. Reasons for this include the utility of the agent and its
      licensing for use in maintaining anesthesia in children over 3 years, but not for
      sedation in PICU in similar doses, for similar periods, in the same group of
      children.

PMID- 15153216
TI  - A case of propofol toxicity: further evidence for a causal mechanism.
AB  - A 5-month-old boy required sedation after a cleft lip repair. He was sedated with
      propofol and intermittent fentanyl, requiring escalating doses over the
      subsequent 48 h. On the second post-operative day he developed a metabolic
      acidosis followed by multiple cardiac dysrhythmias, hepatic and renal failure.
      Propofol was stopped. His multisystem organ failure gradually resolved after
      initiation of charcoal haemoperfusion. Further investigation demonstrated an
      abnormality in acylcarnitine metabolism, similar to that found in one previous
      case report.

PMID- 15153217
TI  - Rhabdomyolysis after intraoperative myelography.
AB  - This case report suggests that the nonionic contrast agents may cause myoclonic
      spasms and seizures like the ionic ones. A 14-year-old female with congenital
      scoliosis was scheduled for T2-L3 scoliosis surgery. She had no medical history
      of a seizure disorder. After a negative wake-up test, myelography was performed
      with iohexol. Myoclonic spasms, disseminated intravascular coagulopathy (DIC) and
      rhabdomyolysis were diagnosed postoperatively. Anaesthesiologists should be aware
      of the complications which may occur after the use of nonionic and water-soluble
      contrast agents.

PMID- 15153218
TI  - Anaesthetic management of infants with glycogen storage disease type II: a
      physiological approach.
AB  - Pompe or Glycogen Storage Disease type II (GSD-II) is a genetic disorder
      affecting both cardiac and skeletal muscle. Historically, patients with the
      infantile form usually die within the first year of life due to cardiac and
      respiratory failure. Recently a promising enzyme replacement therapy has resulted
      in improved clinical outcomes and a resurgence of elective anaesthesia for these
      patients. Understanding the unique cardiac physiology in patients with GSD-II is
      essential to providing safe general anaesthesia.

PMID- 15153219
TI  - Plastic bronchitis: a case report.
AB  - We report a case of perioperative management of a toddler with plastic bronchitis
      complicated by tracheal obstruction. We discuss our management of this case as
      well as the diverse group of patients who may present with this disease. We also
      reviewed the literature regarding medical management of cast bronchitis.

PMID- 15153220
TI  - Osteogenesis imperfecta: different anaesthetic approaches to two paediatric
      cases.

PMID- 15153221
TI  - A combined stage 1 and 2 repair for hypoplastic left heart syndrome: anaesthetic
      considerations.

PMID- 15153223
TI  - Prolonged preoperative fasting periods prescribed by residents in pediatric
      anesthesia.

PMID- 15153224
TI  - Laryngeal web as a cause of upper airway obstruction in children.

PMID- 15153225
TI  - Caudal clonidine in neonates and small infants and respiratory depression.

PMID- 15153227
TI  - Dexmedetomidine in pediatrics: controlled studies needed.

PMID- 15153226
TI  - Preoperative and perioperative management of a patient with Lowe syndrome
      diagnosed to have Fanconi's syndrome.

PMID- 15153229
TI  - Protective ventilation of patients with acute respiratory distress syndrome.
AB  - In a recent issue of the British Journal of Anaesthesia, Moloney and Griffiths
      reviewed clinically pertinent issues surrounding the management of the acute
      respiratory distress syndrome (ARDS) patient, particularly as it pertains to the
      treatment of ventilator induced/associated lung injury (VILI). In addition to
      highlighting the important observations that have contributed to further our
      understanding of the relationship between the mechanical ventilator and
      inflammatory lung injury, the authors also offer a concise reappraisal of the
      clinical strategies used to minimize VILI in ARDS. Special emphasis is placed on
      the theory of biotrauma, which attempts to explain how multi-organ failure may
      develop in patients who ultimately succumb to this syndrome.

PMID- 15153230
TI  - Recently published papers: bugs, fluids, obesity and food.

PMID- 15153231
TI  - How to compare adequacy of algorithms to control blood glucose in the intensive
      care unit?
AB  - Vogelzang et al. retrospectively assessed a derivative marker of blood glucose
      control over time in the intensive care unit (ICU), "the hyperglycemic index"
      (HGI), in relation to outcome. The HGI predicted mortality better than other
      indices of blood glucose control that do not take the duration of hyperglycemia
      into account. This provided further support to the concept of maintaining
      normoglycemia with insulin throughout intensive care in order to improve outcome.
      The HGI was also proposed as a tool to assess performance of glucose control
      algorithms. This, however, implies similar sampling frequency for the compared
      algorithms. Just as we prefer continuous, online display of blood pressure and/or
      cardiac output for optimal titration of inotropes and vasopressors, a continuous
      display of blood glucose levels is mandatory for optimal titration of insulin
      therapy in ICU. We anxiously await the development and validation of such
      devices.

PMID- 15153232
TI  - Pro/con clinical debate: isolation precautions for all intensive care unit
      patients with methicillin-resistant Staphylococcus aureus colonization are
      essential.
AB  - Antibiotic-resistant bacteria are an increasingly common problem in intensive
      care units (ICUs), and they are capable of impacting on patient outcome, the
      ICU's budget and bed availability. This issue, coupled with recent outbreaks of
      illnesses that pose a direct risk to ICU staff (such as SARS [severe acute
      respiratory syndrome]), has led to renewed emphasis on infection control measures
      and practitioners in the ICU. Infection control measures frequently cause
      clinicians to practice in a more time consuming way. As a result it is not
      surprising that ensuring compliance with these measures is not always easy,
      particularly when their benefit is not immediately obvious. In this issue of
      Critical Care, two experts face off over the need to isolate patients infected
      with methicillin-resistant Staphylococcus aureus.

PMID- 15153233
TI  - Clinical review: new technologies for prevention of intravascular catheter
      related infections.
AB  - Intravascular catheters have become essential devices for the management of
      critically and chronically ill patients. However, their use is often associated
      with serious infectious complications, mostly catheter-related bloodstream
      infection (CRBSI), resulting in significant morbidity, increased duration of
      hospitalization, and additional medical costs. The majority of CRBSIs are
      associated with central venous catheters (CVCs), and the relative risk for CRBSI
      is significantly greater with CVCs than with peripheral venous catheters.
      However, most CVC-related infections are preventable, and different measures have
      been implemented to reduce the risk for CRBSI, including maximal barrier
      precautions during catheter insertion, catheter site maintenance, and hub
      handling. The focus of the present review is on new technologies for preventing
      infections that are directed at CVCs. New preventive strategies that have been
      shown to be effective in reducing risk for CRBSI, including the use of catheters
      and dressings impregnated with antiseptics or antibiotics, the use of new hub
      models, and the use of antibiotic lock solutions, are briefly described.

PMID- 15153234
TI  - Clinical review: bedside assessment of alveolar recruitment.
AB  - Recruitment is a dynamic physiological process that refers to the reopening of
      previously gasless lung units. Cumulating evidence has led to a better
      understanding of the rules that govern both recruitment and derecruitment during
      mechanical ventilation of patients with acute respiratory distress syndrome.
      Therefore not only the positive end-expiratory pressure, but also the tidal
      volume, the inspired oxygen fraction, repeated tracheal suctioning as well as
      sedation and paralysis may affect recruitment of acute respiratory distress
      syndrome lungs that are particularly prone to alveolar instability. In the
      present article, we review the recently reported data concerning the
      physiological significance of the pressure-volume curve and its use to assess
      alveolar recruitment. We also describe alternate techniques that have been
      proposed to assess recruitment at the bedside. Whether recruitment should be
      optimized remains an ongoing controversy that warrants further clinical
      investigation.

PMID- 15153235
TI  - Clinical review: influence of vasoactive and other therapies on intestinal and
      hepatic circulations in patients with septic shock.
AB  - The organs of the hepatosplanchnic system are considered to play a key role in
      the development of multiorgan failure during septic shock. Impaired oxygenation
      of the intestinal mucosa can lead to disruption of the intestinal barrier, which
      may promote a vicious cycle of inflammatory response, increased oxygen demand and
      inadequate oxygen supply. Standard septic shock therapy includes supportive
      treatment such as fluid resuscitation, administration of vasopressors (adrenergic
      and nonadrenergic drugs), and respiratory and renal support. These therapies may
      have beneficial or detrimental effects not only on systemic haemodynamics but
      also on splanchnic haemodynamics, at both the macrocirculatory and
      microcirculatory levels. This clinical review focuses on the splanchnic
      haemodynamic and metabolic effects of standard therapies used in patients with
      septic shock, as well as on the recently described nonconventional therapies such
      as vasopressin, prostacyclin and N-acetyl cysteine.

PMID- 15153236
TI  - Bench-to-bedside review: understanding genetic predisposition to sepsis.
AB  - Sepsis is a complex syndrome that develops when the initial, appropriate host
      response to an infection becomes amplified, and is then dysregulated. Among other
      factors, the innate immune system is of central importance to the early
      containment of infection. Death from infection is strongly heritable in human
      populations. Hence, genetic variations that disrupt innate immune sensing of
      infectious organisms could explain the ability of the immune system to respond to
      infection, the diversity of the clinical presentation of sepsis, the response to
      current medical treatment, and the genetic predisposition to infection in each
      individual patient. Such genetic variations may identify patients at high risk
      for the development of sepsis and organ dysfunction during severe infections.
      Single base variations, known as single nucleotide polymorphisms (SNPs), are the
      most commonly used variants. There has been great interest in exploring SNP in
      those genes involved in the inflammatory cascade resulting from the systemic
      inflammatory response to micro organisms. The rationale for studying gene SNPs in
      critical illnesses seeks to identify potential markers of susceptibility,
      severity, and clinical outcome; seeks to identify potential markers for
      responders and non-responders in clinical trials, and seeks to identify targets
      for therapeutic intervention. In this review, we focus on the current state of
      association studies of those genes governing the powerful bacterial infection
      induced inflammation and provide guidelines for future studies describing disease
      associations with genetic variations based on current recommendations. We
      envision a time in the near future when genotyping will be include in the
      standard evaluation of critically ill patients and will help to prioritize a
      therapeutic option.

PMID- 15153238
TI  - Statistics review 10: further nonparametric methods.
AB  - This review introduces nonparametric methods for testing differences between more
      than two groups or treatments. Three of the more common tests are described in
      detail, together with multiple comparison procedures for identifying specific
      differences between pairs of groups.

PMID- 15153237
TI  - Equipment review: an appraisal of the LiDCO plus method of measuring cardiac
      output.
AB  - The LiDCO plus system is a minimally/non-invasive technique of continuous cardiac
      output measurement. In common with all cardiac output monitors this technology
      has both strengths and weaknesses. This review discusses the technological basis
      of the device and its clinical application.

PMID- 15153240
TI  - Preload-independent mechanisms contribute to increased stroke volume following
      large volume saline infusion in normal volunteers: a prospective interventional
      study.
AB  - INTRODUCTION: Resuscitation with saline is a standard initial response to
      hypotension or shock of almost any cause. Saline resuscitation is thought to
      generate an increase in cardiac output through a preload-dependent (increased end
      diastolic volume) augmentation of stroke volume. We sought to confirm this to be
      the mechanism by which high-volume saline administration (comparable to that used
      in resuscitation of shock) results in improved cardiac output in normal healthy
      volunteers. METHODS: Using a standardized protocol, 24 healthy male (group 1) and
      12 healthy mixed sex (group 2) volunteers were infused with 3 l normal (0.9%)
      saline over 3 hours in a prospective interventional study. Individuals were
      studied at baseline and following volume infusion using volumetric
      echocardiography (group 1) or a combination of pulmonary artery catheterization
      and radionuclide cineangiography (group 2). RESULTS: Saline infusion resulted in
      minor effects on heart rate and arterial pressures. Stroke volume index increased
      significantly (by approximately 15-25%; P < 0.0001). Biventricular end-diastolic
      volumes were only inconsistently increased, whereas end-systolic volumes
      decreased almost uniformly. Decreased end-systolic volume contributed as much as
      40-90% to the stroke volume index response. Indices of ventricular contractility
      including ejection fraction, ventricular stroke work and peak systolic
      pressure/end-systolic volume index ratio all increased significantly (minimum P <
      0.01). CONCLUSION: The increase in stroke volume associated with high-volume
      saline infusion into normal individuals is not only mediated by an increase in
      end-diastolic volume, as standard teaching suggests, but also involves a
      consistent and substantial decrease in end-systolic volumes and increases in
      basic indices of cardiac contractility. This phenomenon may be consistent with
      either an increase in biventricular contractility or a decrease in afterload.

PMID- 15153239
TI  - Hyperglycaemic index as a tool to assess glucose control: a retrospective study.
AB  - INTRODUCTION: Critically ill patients may benefit from strict glucose control. An
      objective measure of hyperglycaemia for assessing glucose control in acutely ill
      patients should reflect the magnitude and duration of hyperglycaemia, should be
      independent of the number of measurements, and should not be falsely lowered by
      hypoglycaemic values. The time average of glucose values above the normal range
      meets these requirements. METHODS: A retrospective, single-centre study was
      performed at a 12-bed surgical intensive care unit. From 1990 through 2001 all
      patients over 15 years, staying at least 4 days, were included. Admission type,
      sex, age, Acute Physiology and Chronic Health Evaluation II score and outcome
      were recorded. The hyperglycaemic index (HGI) was defined as the area under the
      curve above the upper limit of normal (glucose level 6.0 mmol/l) divided by the
      total length of stay. HGI, admission glucose, mean morning glucose, mean glucose
      and maximal glucose were calculated for each patient. The relations between these
      measures and 30-day mortality were determined. RESULTS: In 1779 patients with a
      median stay in the intensive care unit of 10 days, the 30-day mortality was 17%.
      A total of 65,528 glucose values were analyzed. Median HGI was 0.9 mmol/l
      (interquartile range 0.3-2.1 mmol/l) in survivors versus 1.8 mmol/l
      (interquartile range 0.7-3.4 mmol/l) in nonsurvivors (P < 0.001). The area under
      the receiver operator characteristic curve was 0.64 for HGI, as compared with
      0.61 and 0.62 for mean morning glucose and mean glucose. HGI was the only
      significant glucose measure in binary logistic regression. CONCLUSION: HGI
      exhibited a better relation with outcome than other glucose indices. HGI is a
      useful measure of glucose control in critically ill patients.

PMID- 15153241
TI  - Case report: purple urine bag syndrome.
AB  - Purple urine bag syndrome (PUBS) was first reported in 1978. PUBS is rare, occurs
      predominantly in constipated women, chronically catheterized and associated with
      some bacterial urinary infections that produce sulphatase/phosphatase. The
      etiology is due to indigo (blue) and indirubin (red) or to their mixture that
      becomes purple. A chain reaction begins in the gastrointestinal tract with
      tryptophan as described in the article.

PMID- 15153242
TI  - Herpes simplex virus type 1 and normal protein permeability in the lungs of
      critically ill patients: a case for low pathogenicity?
AB  - INTRODUCTION: The pathogenicity of late respiratory infections with herpes
      simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four
      critically ill patients with persistent pulmonary infiltrates of unknown origin
      and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at
      7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak
      index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(
      3)/min) was measured. RESULTS: The PLI ranged between 7.5 and 14.0 x 10(-3)/min
      in the study patients. Two patients received a course of acyclovir and all
      survived. CONCLUSIONS: The normal capillary permeability observed in the lungs
      argues against pathogenicity of HSV-1 in the critically ill, and favors that
      isolation of the virus reflects reactivation in the course of serious illness and
      immunodepresssion, rather than primary or superimposed infection in the lungs.

PMID- 15153244
TI  - Selection of functional mutations in the U5-IR stem and loop regions of the Rous
      sarcoma virus genome.
AB  - BACKGROUND: The 5' end of the Rous sarcoma virus (RSV) RNA around the primer
      binding site forms a series of RNA secondary stem/loop structures (U5-IR stem,
      TpsiC interaction region, U5-leader stem) that are required for efficient
      initiation of reverse transcription. The U5-IR stem and loop also encode the U5
      integrase (IN) recognition sequence at the level of DNA such that this region has
      overlapping biological functions in reverse transcription and integration.
      RESULTS: We have investigated the ability of RSV to tolerate mutations in and
      around the U5 IR stem and loop. Through the use of viral libraries with blocks of
      random sequence, we have screened for functional mutants in vivo, growing the
      virus libraries in turkey embryo fibroblasts. The library representing the U5-IR
      stem rapidly selects for clones that maintain the structure of the stem, and is
      subsequently overtaken by wild type sequence. In contrast, in the library
      representing the U5-IR loop, wild type sequence is found after five rounds of
      infection but it does not dominate the virus pool, indicating that the mutant
      sequences identified are able to replicate at or near wild type levels.
      CONCLUSION: These results indicate that the region of the RNA genome in U5
      adjacent to the PBS tolerates much sequence variation even though it is required
      for multiple biological functions in replication. The in vivo selection method
      utilized in this study was capable of detecting complex patterns of selection as
      well as identifying biologically relevant viral mutants.

PMID- 15153243
TI  - Clinically important deep vein thrombosis in the intensive care unit: a survey of
      intensivists.
AB  - INTRODUCTION: Outside the intensive care unit (ICU), clinically important deep
      vein thrombosis (DVT) is usually defined as a symptomatic event that leads to
      objective radiologic confirmation and subsequent treatment. The objective of the
      present survey is to identify the patient factors and radiologic features of
      lower limb DVT that intensivists consider more or less likely to make a DVT
      clinically important in ICU patients. METHODS: Our definition of clinically
      important DVT was a DVT likely to result in short-term or long-term morbidity or
      mortality if left untreated, as opposed to a DVT that is unlikely to have
      important consequences. We asked respondents to indicate the likelihood that
      patient factors and ultrasonographic features make a DVT clinically important
      using a five-point scale (from 1 = much less likely to 5 = much more likely).
      RESULTS: Of the 71 Canadian intensivists who responded, 70 (99%) rated three
      patient factors as most likely to make a DVT clinically important: clinical
      suspicion of pulmonary embolism (mean score 4.6), acute or chronic
      cardiopulmonary morbidity that might limit a patient's ability to tolerate
      pulmonary embolism (score 4.5), and leg symptoms (score 4.2). Of the ultrasound
      features, proximal (score 4.7), large (score 4.2), and totally occlusive (score
      3.9) thrombi were considered the three most important. CONCLUSION: When labeling
      a DVT as clinically important, intensivists rely on different patient specific
      factors and thrombus characteristics than are used to assess the clinical
      importance of DVT outside the ICU. The clinical importance of DVT is influenced
      by unique factors such as cardiopulmonary reserve among mechanically ventilated
      patients.

PMID- 15153245
TI  - Results of chemical pleurodesis with mitoxantrone in malignant pleural effusion
      from breast cancer.
AB  - BACKGROUND: Carcinoma of the breast is the second leading cause of malignant
      pleural effusions. This study reports on the efficacy of mitoxantrone as a
      sclerosing agent in patients with breast cancer who had a pleural effusion as a
      direct consequence of metastatic disease. PATIENTS AND METHODS: Over a 5-year
      period, 114 patients with a known breast malignancy and having recurrent
      symptomatic pleural effusion referred for chest tube drainage and sclerotherapy
      were considered eligible. They had received no prior intrapleural therapy and had
      a predicted survival of >1 month. All of them underwent pleural drainage and
      chemical pleurodesis with mitoxantrone. Survival, complications and response to
      pleurodesis according to clinical and radiographic criteria were recorded. The
      data are expressed as the mean +/- standard error of the mean (SEM) and the
      median. The chi2 test was used for statistical analysis. To assess the prognostic
      value of Karnofsky's performance status score a Cox proportional hazards model
      was used. RESULTS: The mean age of the patients was 53.5 +/- 2.1 years. Effusion
      occurred after 38.2 +/- 6.2 months (range: 1-229 months) after the diagnosis.
      Ipsilateral effusion was seen in 73%, contralateral in 20% and bilateral in 7%.
      Forty patients (35%) had pleural effusion as the first evidence of recurrence.
      The mean volume of effusion drained was 1020 +/- 125 ml and the chest tube was
      removed within 5 days in 82% of patients. Side effects of chemical pleurodesis
      included mainly fever, chest pain, nausea and vomiting. At 30 days 64 patients
      (56.3%) had a complete response (CR) and 30 patients (26.3%) partial response
      (PR) to pleurodesis (overall response: 82.6%). At 60 days the overall response
      was 78.5% (CR:53.5%, PR: 25%). The mean survival was 15.6 +/- 2 months.
      Karnofsky's performance status score was found to be a statistically significant
      predictor. Patients with Karnofsky's performance status score >70 had a median
      survival of 513 days, as opposed to a median survival of only 63 days for
      patients with a Karnofsky's performance status score <30. CONCLUSIONS:
      Mitoxantrone is effective in the treatment of malignant pleural effusion due to
      breast carcinoma with relatively low local or systemic toxicity. Karnofsky's
      performance status score at the time of pleurodesis is predictive of survival.

PMID- 15153246
TI  - Blunt trauma to large vessels: a mathematical study.
AB  - BACKGROUND: Blunt trauma causes short-term compression of some or all parts of
      the chest, abdomen or pelvis and changes hemodynamics of the blood. Short-term
      compression caused by trauma also results in a short-term decrease in the
      diameter of blood vessels. It has been shown that with a sudden change in the
      diameter of a tube or in the direction of the flow, the slower-moving fluid near
      the wall stops or reverses direction, which is known as boundary layer separation
      (BLS). We hypothesized that a sudden change in the diameter of elastic vessel
      that results from compression may lead not only to BLS but also to other
      hemodynamic changes that can damage endothelium. METHODS: We applied Navier
      Stokes, multiphase and boundary layer equations to examine such stress. The
      method of approximation to solve the BL equations was used. Experiments were
      conducted in an aerodynamic tube, where incident flow velocity and weight of
      carriage with particles before and after blowing were measured. RESULTS: We found
      that sudden compression resulting from trauma leads to (1) BLS on the curved
      surface of the vessel wall; (2) transfer of laminar boundary layer into turbulent
      boundary layer. Damage to the endothelium can occur if compression is at least
      25% and velocity is greater than 2.4 m/s or if compression is at least 10% and
      velocity is greater than 2.9 m/s. CONCLUSION: Our research may point up new ways
      of reducing the damage from blunt trauma to large vessels. It has the potential
      for improvement of safety features of motor vehicles. This work will better our
      understanding of the precise mechanics and critical variables involved in
      diagnosis and prevention of blunt trauma to large vessels.

PMID- 15153247
TI  - Lichen planus and Hepatitis C: a case-control study.
AB  - BACKGROUND: The association of lichen planus with hepatitis C (HCV) has been
      widely reported in the literature. However, there are wide geographical
      variations in the reported prevalence of HCV infection in patients with lichen
      planus. This study was conducted to determine the frequency of hepatitis C in
      Iranian patients with lichen planus at Razi hospital, Tehran. METHODS: During the
      years 1997 and 1998, 146 cases of lichen planus, 78 (53.1%) women and 69 (46.9%)
      men were diagnosed. They were diagnosed on the basis of the usual clinical
      features and, if necessary, typical histological findings. The patients were
      screened for the presence of anti-HCV antibodies by third generation ELISA and
      liver function tests. We used the results from screening of blood donors for anti
      HCV (carried out by Iranian Blood Transfusion Organization) for comparison as the
      control group. RESULTS: Anti-HCV antibodies were detected in seven cases (4.8%).
      This was significantly higher than that of the blood donors' antibodies (p <
      0.001). The odds ratio was 50.37(21.45-112.24). A statistically significant
      association was demonstrated between erosive lichen planus and HCV infection.
      Liver function tests were not significantly different between HCV infected and
      non-infected patients. CONCLUSION: HCV appears to have an etiologic role for
      lichen planus in Iranian patients. On the other hand, liver function tests are
      not good screening means for HCV infection.

PMID- 15153248
TI  - Early rectal stenosis following stapled rectal mucosectomy for hemorrhoids.
AB  - BACKGROUND: Within the last years, stapled rectal mucosectomy (SRM) has become a
      widely accepted procedure for second and third degree hemorrhoids. One of the
      delayed complications is a stenosis of the lower rectum. In order to evaluate the
      specific problem of rectal stenosis following SRM we reviewed our data with
      special respect to potential predictive factors or stenotic events. METHODS: A
      retrospective analysis of 419 consecutive patients, which underwent SRM from
      December 1998 to August 2003 was performed. Only patients with at least one
      follow-up check were evaluated, thus the analysis includes 289 patients with a
      mean follow-up of 281 days (+/-18 days). For statistic analysis the groups with
      and without stenosis were evaluated using the Chi-Square Test, using the Kaplan
      Meier statistic the actuarial incidence for rectal stenosis was plotted. RESULTS:
      Rectal stenosis was observed in 9 patients (3.1%), eight of these stenoses were
      detected within the first 100 days after surgery; the median time to stenosis was
      95 days. Only one patient had a rectal stenosis after more than one year. 8 of
      the 9 patients had no obstructive symptoms, however the remaining patients
      complained of obstructive defecation and underwent surgery for transanal
      strictureplasty with electrocautery. A statistical analysis revealed that
      patients with stenosis had significantly more often prior treatment for
      hemorrhoids (p < 0.01). According to the SRM only severe postoperative pain was
      significantly associated with stenoses (p < 0.01). Other factors, such as gender
      (p = 0.11), surgical technique (p = 0.25), revision (p = 0.79) or histological
      evidence of squamous skin (p = 0.69) showed no significance. CONCLUSION: Rectal
      stenosis is an uncommon event after SRM. Early stenosis will occur within the
      first three months after surgery. The majority of the stenoses are without
      clinical relevance. Only one of nine patients had to undergo surgery for a
      relevant stenosis. The predictive factor for stenosis in the patient
      characteristics is previous interventions for hemorrhoids, severe postoperative
      pain might also predict rectal stenosis.

PMID- 15153249
TI  - Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of
      the impact on patient time and activities.
AB  - BACKGROUND: Patients with cancer must make frequent visits to the clinic not only
      for chemotherapy but also for the management of treatment-related adverse
      effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive
      chemotherapy, has substantial clinical and economic consequences. Colony
      stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence
      of neutropenia, but the clinic visits for these treatments can disrupt patients'
      routines and activities. METHODS: We surveyed patients to assess how clinic
      visits for treatment with chemotherapy and the management of neutropenia affect
      their time and activities. RESULTS: The mean amounts of time affected by these
      visits ranged from approximately 109 hours (hospitalization for neutropenia) and
      8 hours (physician and chemotherapy) to less than 3 hours (laboratory and
      treatment with filgrastim or pegfilgrastim). The visits for filgrastim or
      pegfilgrastim were comparable in length, but treatment with filgrastim requires
      several visits per chemotherapy cycle and treatment with pegfilgrastim requires
      only 1 visit. CONCLUSIONS: This study provides useful information for future
      modelling of additional factors such as disease status and chemotherapy schedule
      and provides information that should be considered in managing chemotherapy
      induced neutropenia.

PMID- 15153252
TI  - Out of the box. Second National Congress of the Brazilian Food and Nutrition
      Society Council.

PMID- 15153251
TI  - Dietary patterns and dietary makeovers.

PMID- 15153250
TI  - Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene
      expression.
AB  - BACKGROUND: Precise control of developmental and cell-specific expression of the
      brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal
      development and the diverse functions of BDNF in the adult organism. We
      previously showed that the zebrafish BDNF gene has multiple promoters. The
      complexity of the promoter structure and the mechanisms that mediate
      developmental and cell-specific expression are still incompletely understood.
      RESULTS: Comparison of pufferfish and zebrafish BDNF gene sequences as well as 5'
      RACE revealed three additional 5' exons and associated promoters. RT-PCR with
      exon-specific primers showed differential developmental and organ-specific
      expression. Two exons were detected in the embryo before transcription starts. Of
      the adult organs examined, the heart expressed a single 5' exon whereas the
      brain, liver and eyes expressed four of the seven 5' exons. Three of the seven 5'
      exons were not detectable by RT-PCR. Injection of promoter/GFP constructs into
      embryos revealed distinct expression patterns. The 3' flank profoundly affected
      expression in a position-dependent manner and a highly conserved sequence (HCS1)
      present in 5' exon 1c in a dehancer-like manner. CONCLUSIONS: The zebrafish BDNF
      gene is as complex in its promoter structure and patterns of differential
      promoter expression as is its murine counterpart. The expression of two of the
      promoters appears to be regulated in a temporally and/or spatially highly
      circumscribed fashion. The 3' flank has a position-dependent effect on
      expression, either by affecting transcription termination or post-transcriptional
      steps. HCS1, a highly conserved sequence in 5' exon 1c, restricts expression to
      primary sensory neurons. The tools are now available for detailed genetic and
      molecular analyses of zebrafish BDNF gene expression.

PMID- 15153253
TI  - Cross-cultural comparison of growth, maturation and adiposity indices of two
      contrasting adolescent populations in rural Senegal (West Africa) and Martinique
      (Caribbean).
AB  - OBJECTIVES: To stress the importance of social and environment (nutritional)
      factors in determining the growth spurt during puberty and the risk of excessive
      adiposity, two contrasting adolescent populations, one from a rural area of
      Senegal (West Africa) and the other from Martinique (French West Indies), were
      compared. DESIGN: Cross-cultural comparison of contrasting populations.
      Adolescents from Senegal belonged to a cohort followed up since 1995. Adolescents
      from Martinique participated in a cross-sectional nutritional survey that covered
      the entire island. SUBJECTS: A total of 507 adolescents (mean age: 14.3+/-0.7
      years) from Senegal (319 girls and 188 boys) and 703 adolescents from Martinique
      (351 boys and 352 girls) were surveyed. RESULTS: Differences in growth and
      maturation were striking: boys in Martinique were 22.7 kg heavier and 20.1 cm
      taller than boys in Senegal. Differences were less important for girls but still
      evident: 12.6 kg in weight and 10.5 cm in stature. In Senegal, there were
      virtually no overweight adolescents, but 18% of girls and 50% of boys could be
      considered as malnourished. In Martinique, 19% of girls and 23% of boys were
      overweight or obese. Adolescent girls from Martinique were also sexually more
      mature than adolescent girls from Senegal. When comparisons were repeated after
      Senegalese girls reached menarche, differences in weight and body mass index
      disappeared, but Senegalese girls were still shorter than girls from Martinique.
      CONCLUSIONS: Adolescents are extremely susceptible to nutritional changes and
      their particular situation needs to be incorporated into nutritional prevention
      programmes.

PMID- 15153254
TI  - A longitudinal assessment of the diet and growth of malnourished children
      participating in nutrition rehabilitation centres in Accra, Ghana.
AB  - OBJECTIVE: To examine the adoption of feeding recommendations among caregivers of
      children recuperating from malnutrition and assess the determinants of growth of
      children attending a nutrition rehabilitation centre (NRC) in Accra, Ghana.
      DESIGN: Longitudinal study in which attendance and maternal programme
      participation were recorded daily and children's anthropometry and dietary intake
      were measured at four time points (admission, interim, exit, post-exit) at the
      NRC and participants' homes. SETTING: NRCs at four polyclinics and participants'
      homes in Accra, Ghana. SUBJECTS: One hundred and eight caregivers and their 116
      children referred to an NRC between November 1999 and July 2000. RESULTS: Most
      caregivers attended the NRC sporadically (effective length of stay was 1.4+/-0.1
      months). Use of NRC-promoted foods in the home after discharge was low due to
      inaccessibility of the food items, lack of preparation knowledge or money, child
      preferences and the common practice of purchasing ready-to-eat foods. Although
      there were significant increases in children's weight-for-age (P=0.048) and
      weight-for-height (P=0.002) Z-scores between enrollment and discharge, most
      children discontinued programme participation before adequate recuperation.
      CONCLUSIONS: The NRC education did not address the use of street foods for child
      feeding and was unsuccessful in changing in-home feeding behaviour. The
      prominence of street foods in children's diets warrants re-evaluation of the
      NRC's educational approaches to enhance their responsiveness to caregivers' needs
      and effectiveness for the continued recuperation of malnourished children at
      home. NRC feeding strategies need improvement to ensure adequate provision of
      energy and nutrients to support catch-up growth in children.

PMID- 15153255
TI  - Breast-feeding at 12 months of age and dietary habits among breast-fed and non
      breast-fed infants.
AB  - OBJECTIVE: To analyse factors associated with breast-feeding and use of sweetened
      drinks at 12 months, and to compare dietary habits among breast-fed and non
      breast-fed infants. DESIGN: Data were collected by a semi-quantitative food
      frequency questionnaire filled in by the parents. SETTING: National dietary
      survey in Norway. SUBJECTS: In total, 1932 12-month-old infants were included.
      RESULTS: At 12 months, 36% of the infants were breast-fed. The odds of breast
      feeding at this age were more than doubled both for mothers > or =35 years
      compared with mothers <25 years and for mothers in the highest educational group
      compared with mothers in the lowest. A negative association was found for
      maternal smoking, and the odds of breast-feeding were 40% lower for mothers who
      smoked than for non-smokers. Some dietary differences were observed between
      breast-fed and non-breast-fed infants apart from intake of milk. In particular,
      breast-fed infants had a significantly lower daily intake of sweetened drinks
      than non-breast-fed infants and a 16% lower mean daily intake of added sugars
      (P<0.001). Furthermore, breast-fed infants had 30% higher odds of not receiving
      sweetened drinks daily, compared with non-breast-fed infants. CONCLUSIONS:
      Maternal age, education and smoking status were important factors for breast
      feeding at 12 months. Breast-fed infants had lower intakes of sweetened drinks
      and added sugars than non-breast-fed infants. From a public health perspective,
      continued promotion of breast-feeding is needed to reduce inequalities in breast
      feeding. Moreover, prevention of high intakes of sweetened drinks and added
      sugars should start in infancy.

PMID- 15153256
TI  - Child-feeding strategies of African American women according to stage of change
      for fruit and vegetable consumption.
AB  - OBJECTIVE: To examine the relationship between child-feeding strategies and the
      stage of change for fruit and vegetable consumption of low-income African
      American women. DESIGN: Mothers were asked to think aloud as they shopped for
      groceries and prepared a meal for their family. Verbalisations were audio-taped
      and transcribed. Transcripts were coded. Coded segments were sorted according to
      stage of change of the women who made the verbalisation. Themes were identified
      and analysed for differences across the stages of change. Child-feeding
      strategies and factors influencing provision of fruits and vegetables to children
      were identified through content analysis procedures. SETTING/SUBJECTS: Seventy
      women, aged 18 to 45 years, were classified by stage of change (10 to 18 per
      stage) based on self-reported intakes of fruits and vegetables and intention to
      increase intake. Women on average had two to three children less than 12 years of
      age and tended to be single heads of households, with about half having some
      college or technical training. RESULTS: According to the women's comments, food
      preferences of children were important considerations for women in all stages
      regarding their food choice behaviours. Women in the later stages reported using
      more positive child-feeding strategies to promote the intake of fruit and
      vegetables, including positive role-modelling and methods related to food
      purchasing, preparation and meal planning. CONCLUSIONS: Promoting mothers'
      movement to more advanced stages of change for fruit and vegetable intake may
      result in the use of more positive child-feeding strategies and therefore
      contribute to increased fruit and vegetable intake by children.

PMID- 15153257
TI  - Dietary and socio-economic factors associated with overweight and obesity in a
      southern French population.
AB  - OBJECTIVE: To investigate the socio-economic and dietary factors associated with
      overweight and obesity, respectively, in southern France. DESIGN: Cross-sectional
      analysis of socio-economic, lifestyle and nutritional characteristics of a
      representative population sample. A questionnaire elicited information on
      anthropometric measurements, socio-economic factors, physical activity, tobacco
      use, and alcohol and food intakes. Non-parametric tests, multiple linear
      regression models and correspondence factorial analysis (CFA) were used to
      estimate the association of the various factors with overweight and obesity.
      SETTING: French Southwest and Mediterranean areas. SUBJECTS: In total, 1169
      subjects (578 women and 552 men), aged 30-77 years, were recruited at random.
      RESULTS: Overweight and obesity were associated with age and education in both
      genders, reproductive factors in women and tobacco use in men. A few dietary
      factors were identified (high energy intake and low intake of carbohydrates), but
      all these variables explained little of the variation (18.5% in women and 14.6%
      in men). The CFA further investigated the association of lifestyle and
      nutritional factors, giving more weight to nutritional behaviour for overweight
      men and women. Factors for obesity differed from those for overweight by being
      different in men and women, possibly related to psychological behaviour, and
      there were fewer of them, suggesting an insufficient coverage by the usual
      questionnaires. CONCLUSIONS: Overweight and obesity appear as two different
      entities. Energy imbalance induced by various lifestyle factors plays a major
      role in the development of overweight, whereas obesity represents a more complex
      entity where psychological and genetic factors that are difficult to assess may
      be more important. General nutritional guidelines appear more adapted to the
      prevention of overweight than to that of obesity, and individual counselling to
      the prevention of obesity.

PMID- 15153258
TI  - Anthropometry of women of childbearing age in Morocco: body composition and
      prevalence of overweight and obesity.
AB  - OBJECTIVE: To determine the prevalence of obesity and body fat distribution of
      Moroccan women of childbearing age, using a panel of anthropometric measurements.
      DESIGN AND SETTING: A cross-sectional survey conducted in 1995 in an agricultural
      community, El Jadida province of Morocco. Weight, height, waist and hip
      circumferences and triceps, biceps, subscapular and supra-iliac skinfold
      thicknesses were measured. Body mass index (BMI), waist/hip ratio (WHR), sum of
      all and sum of trunk skinfold thicknesses were determined. SUBJECTS: In total,
      1269 women aged 15-49 years from urban and rural areas were surveyed. RESULTS:
      The means of all anthropometric measurements including body fat were higher in
      urban than in rural women and increased with age. Trunk fat contributed 50% of
      total fat. Globally, 4.7% of women were underweight (BMI<18.5 kg m(-2)), 35.2%
      were overweight or obese (BMI> or =25 kg m(-2)), 10.1% were obese (BMI> or =30 kg
      m(-2)) and 16.8% had central obesity (WHR>0.85). The prevalence of overweight and
      obesity was higher in the urban than in the rural area. Underweight prevalence
      decreased with age, whereas that of overweight and obesity increased. All
      anthropometric parameters adjusted for age increased with the increase of BMI and
      WHR. CONCLUSIONS: Although undernutrition is still prevalent, there is an
      alarming prevalence of overweight and obesity in Moroccan women of childbearing
      age. The results indicate a shift in this country from the problem of dietary
      deficiency to the problem of dietary excess, and alert one to the necessity of
      establishing an intervention to prevent obesity-related diseases. It is necessary
      to address which of the anthropometric variables studied here is the best
      predictor of obesity-related diseases in this population.

PMID- 15153259
TI  - The Medi-RIVAGE study (Mediterranean Diet, Cardiovascular Risks and Gene
      Polymorphisms): rationale, recruitment, design, dietary intervention and baseline
      characteristics of participants.
AB  - OBJECTIVE: To report the rationale, recruitment, design, dietary intervention and
      baseline characteristics of participants in the Medi-RIVAGE study (Mediterranean
      Diet, Cardiovascular Risks and Gene Polymorphisms). DESIGN: A randomised,
      parallel trial comparing a new nutritional programme with a conventional
      programme. SETTING: Centre for Detection and Prevention of Arteriosclerosis,
      Timone University Hospital, Marseille, France, and collaborating teams. SUBJECTS:
      Two hundred and twelve male and female volunteers with at least one
      cardiovascular risk factor. INTERVENTION: A Mediterranean-type diet characterised
      mainly by the quality of fatty acids, amount of fish, vegetable foodstuffs and
      fibre was proposed and compared with a usually prescribed, low-fat/cholesterol
      diet. Body mass index, fasting lipids and lipoproteins, apolipoproteins, glucose,
      insulin and homocysteine were the main outcome measures. Gene polymorphisms of
      interest were determined. RESULTS: Characteristics of men in the two arms were
      comparable with regard to sociodemographic variables, and clinical and biological
      cardiovascular risk factors. There were few differences between the groups of
      women (cholesterol-related parameters, P<0.05). There was no difference between
      arms in allelic distribution of the gene polymorphisms studied. Saturated fat and
      protein intakes were high while carbohydrate and fibre intakes were low, but with
      no difference between arms. Overall, the nutritional markers were comparable in
      both arms with few exceptions. Correlations between nutritional intakes and
      plasma nutrient levels ranged from 0.19 (beta-carotene) to 0.47 (folate).
      CONCLUSIONS: The comparability of the two arms is notable and warrants a low risk
      of biases. Current diet departs from the traditional Mediterranean one. The
      assessment of nutritional intake is validated by correlations obtained between
      dietary intake and relevant biomarkers. This will be important to estimate
      participant compliance and to analyse intervention data.

PMID- 15153260
TI  - The impact of high non-starch polysaccharide intake on serum micronutrient
      concentrations in a cohort of women.
AB  - OBJECTIVE: Many public health campaigns encourage increased fibre consumption,
      but short-term studies suggest that various components of dietary fibre inhibit
      the absorption of certain micronutrients including carotenoids. These do not take
      into account long-term adaptation to nutrient intake levels. We aimed to
      investigate the effect of non-starch polysaccharide (NSP) fibre on plasma
      micronutrient concentrations in a large free-living population consuming their
      usual diet. DESIGN: Prospective cohort study. Semi-weighed 4-day food diaries
      were analysed for micronutrient and NSP fibre intakes. Blood samples were taken
      and analysed for carotenoids, vitamin A, vitamin E, thiamine, riboflavin, vitamin
      B6, vitamin B12, folic acid, vitamin C and trace metals. SETTING: Participants in
      a large national cohort study who lived within 30 miles of Leeds. SUBJECTS: Two
      hundred and eighty-three middle-aged women. RESULTS: The association between NSP
      intake and plasma nutrient concentrations was assessed taking into account
      nutrient intakes and other dietary and lifestyle factors. Higher levels of NSP
      were not associated with lower plasma concentrations of the micronutrients
      measured, even allowing for the higher nutrient levels generally found in high
      fibre foods. CONCLUSIONS: Amongst middle-aged women we have shown that current
      guidelines for increasing the population's NSP consumption can be safely applied.
      Such guidelines are unlikely to reduce serum micronutrient concentrations,
      although other, more vulnerable population groups may benefit from further
      investigation.

PMID- 15153261
TI  - The origin of Guideline Daily Amounts and the Food Standards Agency's guidance on
      what counts as 'a lot' and 'a little'.
AB  - OBJECTIVE: This paper provides the rationale for the Guideline Daily Amounts
      (GDAs) for fat, saturated fat and other nutrients that appear on food labels in
      the UK. These GDAs are provided voluntarily by manufacturers and retailers and
      were developed to help people make better use of nutrition labelling--the format
      of which is prescribed by the European Union's nutrition labelling directive. The
      paper also describes the basis to some Rules of Thumb for what counts as 'a lot'
      or 'a little' of fat, saturated fat and other nutrients, in an individual food.
      DESIGN: The paper gives the background to, and purpose of, the GDAs and Rules of
      Thumb and explains how they were calculated. It briefly describes their
      subsequent usage by food producers and others. RESULTS: Both GDAs and the Rules
      of Thumb first appeared in a leaflet developed by the authors and published in
      1996 by the Ministry of Agriculture, Fisheries and Food. GDAs for fat, saturated
      fat and energy were adopted subsequently by the Institute of Grocery Distribution
      and then by many retailers and some manufacturers. The Rules of Thumb for fat,
      saturated fat, sugar and sodium have recently been republished in some leaflets
      published by the Food Standards Agency in the UK. CONCLUSIONS: GDAs and Rules of
      Thumb may provide useful ways of helping consumers make sense of nutrition
      labelling. The current GDAs and the Rules of Thumb could usefully be updated in
      the light of recent developments.

PMID- 15153262
TI  - Can a simple measure of vigorous physical activity predict future mortality?
      Results from the OXCHECK study.
AB  - BACKGROUND: As epidemiological studies have become more complex, demands for
      short, easily administered measures of risk factors have increased. This study
      investigates whether such a measure of physical activity is associated with the
      risk of death from all causes and death from specific causes. METHODS: A
      prospective follow-up study of 11,090 men and women, aged 35-64 years, recruited
      from five UK general practices who responded to a postal questionnaire in 1989.
      Self-reported frequency of vigorous-intensity physical activity and data on
      confounding factors were collected at baseline survey. Death notifications up to
      31 December 2001 were provided by the Office for National Statistics. The
      relative risk (and 95% confidence interval) of dying associated with each level
      of exposure to physical activity was estimated by the hazard ratio in a series of
      Cox regression models. RESULTS: After >10 years' follow-up there were 825 deaths
      among the 10 522 subjects with no previous history of angina or myocardial
      infarction. Participation in vigorous exercise was associated with a
      significantly lower risk of all-cause mortality. Similar associations were found
      for ischaemic heart disease and cancer mortality, although the relationships were
      not significant at the 5% level. CONCLUSIONS: Simple measures of self-reported
      vigorous physical activity are associated with the risk of future mortality, at
      least all-cause mortality in a somewhat selected group. Interpretation of the
      finding should be treated with caution due to the reliance on self-report and the
      possibility that residual confounding may underlie the associations. Because
      moderate-intensity physical activity is also beneficial to health, short physical
      activity questionnaires should include measures of such physical activity in the
      future.

PMID- 15153263
TI  - Two important exceptions to the relationship between energy density and fat
      content: foods with reduced-fat claims and high-fat vegetable-based dishes.
AB  - OBJECTIVE: To test the hypothesis that many foods with reduced-fat (RF) claims
      are relatively energy-dense and that high-fat (HF) vegetable-based dishes are
      relatively energy-dilute. DESIGN: Nutrient data were collected from available
      foods in Melbourne supermarkets that had an RF claim and a full-fat (FF)
      equivalent. Nutrient analyses were also conducted on recipes for HF vegetable
      based dishes that had more than 30% energy from fat but less than 10% from
      saturated fat. The dietary intake data (beverages removed) from the 1995 National
      Nutrition Survey were used for the reference relationships between energy density
      (ED) and percentage energy as fat and carbohydrate and percentage of water by
      weight. STATISTICS: Linear regression modelled relationships of macronutrients
      and ED. Paired t-tests compared observed and predicted reductions in the ED of RF
      foods compared with FF equivalents. RESULTS: Both FF and RF foods were more
      energy-dense than the Australian diet and the HF vegetable-based dishes were less
      energy-dense. The Australian diet showed significant relationships with ED, which
      were positive for percentage energy as fat and negative for percentage energy as
      carbohydrate. There were no such relationships for the products with RF claims or
      for the HF vegetable-based dishes. CONCLUSION: While, overall, a reduced-fat diet
      is relatively energy-dilute and is likely to protect against weight gain, there
      appear to be two important exceptions. A high intake of products with RF claims
      could lead to a relatively energy-dense diet and thus promote weight gain.
      Alternatively, a high intake of vegetable-based foods, even with substantial
      added fat, could reduce ED and protect against weight gain.

PMID- 15153264
TI  - The iodine content of Norwegian foods and diets.
AB  - OBJECTIVES: To examine dietary iodine sources and to estimate the dietary iodine
      intake of the Norwegian population. DESIGN: Food iodine analyses carried out in
      Norway during the last 10 years were compiled, and iodine intake calculated on
      the basis of food intake data from nation-wide dietary surveys among children and
      adults. The food intake of adults was measured by a self-administrated food
      frequency questionnaire, which covered habitual diet during the past year. The
      food intake of children was measured by dietary record during four consecutive
      days. SETTING: Neither household nor industrial iodisation of salt is mandatory
      in Norway, but some brands of table salt have 5 microg of iodine added per gram
      of NaCl. In spite of this, the population has been considered iodine-replete for
      decades, i.e. having an iodine intake well above the Recommended Dietary
      Allowance of 150 microg day(-1). This assumption has not been substantiated by
      dietary surveys. SUBJECTS: The adults included 1374 females and 1298 males aged
      16-79 years. The children included 185 girls and 206 boys aged 4 years, 411 girls
      and 404 boys aged 9 years, and 517 girls and 492 boys aged 13 years. RESULTS: The
      calculated iodine intake was in the range of 100-250 microg day(-1) in the
      majority of the adult population. The mean iodine intake was 136 microg day(-1)
      (170 microg I/10 MJ) among women and 176 microg day(-1) (161 microg I/10 MJ)
      among men. For children the iodine intake was in the range of 100-120 microg day(
      1). Milk and dairy products contributed approximately 55% and 70% of the dietary
      iodine intake in adults and children, respectively. Fish contributed more than
      20% of the iodine intake in adults and about 10% in children. The iodine
      contribution of drinking water was negligible. CONCLUSIONS: While fish has the
      highest natural concentration of iodine and as such is an excellent iodine
      source, milk and diary products are the main determinants of iodine intake in the
      Norwegian population. Iodisation of cow fodder has been mandatory in Norway since
      1950 and provides an efficient alternative to universal salt iodisation. Our
      results show that the dietary iodine intake of adults is in the range considered
      to be sufficient. The dietary intake of iodine was at recommended levels among
      the youngest children; however, it decreased among adolescents, especially among
      girls.

PMID- 15153265
TI  - Effect of the choice of food composition table on nutrient estimates: a
      comparison between the British and American (Chilean) tables.
AB  - OBJECTIVE: To determine the level of agreement between the American (Chilean) and
      British food composition tables in estimating intakes of macronutrients and
      antioxidants. DESIGN, SETTING AND SUBJECTS: Information based on a food-frequency
      questionnaire with emphasis on antioxidants was collected from 95 Chileans aged
      24-28 years. Nutritional composition was analysed using the British table of food
      composition and the American table of food composition modified by Chilean food
      items. Mean differences and limits of agreement (LOAs) of estimated intake were
      assessed. RESULTS: Mean differences between the two tables of food composition
      ranged from 5.3% to 8.9% higher estimates when using the American (Chilean) table
      for macronutrients. For micronutrients, a bias towards a higher mean was observed
      for vitamin E, iron and magnesium when the American (Chilean) table was used, but
      the opposite was observed for vitamin A and selenium. The intra-class correlation
      coefficient (ICC) ranged from 0.86 (95% confidence interval (CI) 0.81-0.91) to
      0.998 (95% CI 0.995-1.00), indicating high to excellent agreement. LOAs for
      macronutrients and vitamins A and C were satisfactory, as they were sufficiently
      narrow. There was more uncertainty for other micronutrients. CONCLUSION: The
      American table gives relative overestimates of macronutrients in comparison to
      the British table, but the relative biases for micronutrients are inconsistent.
      Estimates of agreement between the two food composition tables provide
      reassurance that results are interchangeable for the majority of nutrients.

PMID- 15153266
TI  - WHO global strategy on diet, physical activity and health.Editorial.

PMID- 15153267
TI  - Out of the box. The WHO strategy on diet, physical activity and health.

PMID- 15153268
TI  - Why the Bush administration and the global sugar industry are determined to
      demolish the 2004 WHO global strategy on diet, physical activity and health.
AB  - OBJECTIVE: To indicate why the world's most powerful nation state and one
      powerful sector of the food and drink production and manufacturing industry are
      determined to demolish the 2004 WHO (World Health Organization) global strategy
      on diet, physical activity and health, and to disassociate it from the 2003
      WHO/FAO (Food and Agriculture Organization) expert report on diet, nutrition and
      the prevention of chronic diseases, which with its background papers is the
      immediate scientific basis for the strategy. To encourage representatives of
      nation states at the 2004 WHO World Health Assembly to support the strategy
      together with the report, so that the strategy is explicit and quantified, and
      responds to the need expressed by member states at the 2002 World Health
      Assembly. This is for an effective global strategy to prevent and control chronic
      diseases whose prevalence is increased by nutrient-poor food low in vegetables
      and fruits and high in energy-dense fatty, sugary and/or salty foods and drinks
      and also by physical inactivity. Of these diseases, obesity, diabetes,
      cardiovascular diseases and cancers of several sites are now the chief causes of
      morbidity and mortality in most countries in the world. METHOD: A summary of the
      global strategy and its roots in scientific knowledge accumulated over the last
      half-century. Reasons why the global strategy and the expert report are opposed
      by the current US government and the world sugar industry, with some reference to
      modern historical context. A summary of the trajectory of the global strategy
      since its first draft made in early 2003, and a further summary of its
      weaknesses, strengths and potential. CONCLUSION: The 2004 WHO global strategy and
      the 2003 WHO/FAO expert report are perceived by the current US administration as
      an impediment to US trade and international policy, within a general context of
      current US government hostility to the UN (United Nations) system as a brake on
      the exercise of its power as the world's dominant nation. Policy-makers
      throughout the world should be aware of the contexts of current pressures put on
      them by powerful nation states and sectors of industry whose ideologies and
      commercial interests are challenged by international initiatives designed to
      improve public health and to leave a better legacy for future generations.

PMID- 15153269
TI  - Why a global strategy on diet, physical activity and health? The growing burden
      of non-communicable diseases.

PMID- 15153270
TI  - The feast of the assumptions.

PMID- 15153271
TI  - Protein/energy ratios of current diets in developed and developing countries
      compared with a safe protein/energy ratio: implications for recommended protein
      and amino acid intakes.
AB  - Revised estimates of protein and amino acid requirements are under discussion by
      the Food and Agriculture Organization (FAO)/World Health Organizaion (WHO), and
      have been proposed in a recent report on Dietary Reference Intakes (DRIs) from
      the USA. The nature and magnitude of these requirements are not entirely
      resolved, and no consideration has been given to the potential influence of
      metabolic adaptation on dietary requirements. We have examined the implications
      of these new values, and of the conceptual metabolic framework in which they are
      used, for defining the nutritional adequacy of protein intakes in developed and
      developing countries. We have expressed proposed values for protein requirements
      in relation to energy requirements, predicted for physical activity levels of
      1.5, 1.75 and 2.0 times basal metabolic rate, in order to generate reference
      ratios for protein energy/total energy (reference P/E ratio) as a function of
      age, body weight, gender and physical activity level. Proposed values for amino
      acid requirements have been used to adjust the available digestible P/E ratio of
      foods and diets for protein quality. Focusing on the diets of UK omnivores and
      vegetarians and on diets in India, the risk of protein deficiency is evaluated
      from a comparison of P/E ratios of metabolic requirements with protein-quality
      adjusted P/E ratios of intakes. A qualitative and conservative estimate of risk
      of deficiency is made by comparing the adjusted P/E ratio of the intake with a
      reference P/E ratio calculated for age, body weight, gender and physical activity
      according to FAO/WHO/United Nations University. A semi-quantitative estimate of
      risk of deficiency has also been made by the cut point approach, calculated as
      the proportion of the intake distribution below the mean P/E ratio of the
      requirement. Values for the quality-adjusted P/E ratio of the diet range from
      0.126 for the UK omnivore diet to 0.054 for a rice-based diet of adults in West
      Bengal, which is lysine-limited, falling to 0.050 for 1-year-old children. The
      reference P/E ratio for men and women increases with age, is higher for females
      than males, is higher for small compared with large adults at any age and
      decreases with physical activity. Thus if a particular diet is potentially
      limiting in protein, protein deficiency is most likely in large, elderly
      sedentary women followed by the adolescent female and least likely in moderately
      active young children, the opposite of what has usually been assumed. Within the
      currently accepted framework, the diets do not meet the protein needs of the
      entire population of the UK, have a significant risk of deficiency throughout
      India for all except extremely active small adults, and are grossly inadequate
      for all population groups, apart from physically active young children in West
      Bengal, regardless of body weight or level of food intake. The lysine limitation
      of the cereal-based Indian diets is dependent on the choice of lysine requirement
      values from the published range. We consider that the value selected is too high,
      because of uncertainties and inconsistencies in the approaches used. A more
      appropriate choice from the lower end of the range would remove the lysine
      limitation of cereal-based diets, and reduce some of the perceived risk of
      deficiency. However, diets remain limited by the amount of digestible protein for
      many population groups, especially in West Bengal. In the context of risk
      management, one option would be to accept the current values and the conceptual
      metabolic framework within which they have been derived. This would have major
      implications for the supplies of high-quality protein to the developing
      countries. An alternative option would be to re-evaluate the currently proposed
      values for the requirements for protein and amino acids. We conclude that the
      choice of values for the adult lysine requirement should be re-evaluated and that
      serious consideration should be given to the extent to which adaptive mechanisms
      might enable the metabolic requirement for protein to be met from current
      intakes. This will entail a better understanding of the relationships between
      dietary protein and health.

PMID- 15153272
TI  - A review of the epidemiological evidence for the 'antioxidant hypothesis'.
AB  - OBJECTIVE: The British Nutrition Foundation was recently commissioned by the Food
      Standards Agency to conduct a review of the government's research programme on
      Antioxidants in Food. Part of this work involved an independent review of the
      scientific literature on the role of antioxidants in chronic disease prevention,
      which is presented in this paper. BACKGROUND: There is consistent evidence that
      diets rich in fruit and vegetables and other plant foods are associated with
      moderately lower overall mortality rates and lower death rates from
      cardiovascular disease and some types of cancer. The 'antioxidant hypothesis'
      proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients
      afford protection against chronic diseases by decreasing oxidative damage.
      RESULTS: Although scientific rationale and observational studies have been
      convincing, randomised primary and secondary intervention trials have failed to
      show any consistent benefit from the use of antioxidant supplements on
      cardiovascular disease or cancer risk, with some trials even suggesting possible
      harm in certain subgroups. These trials have usually involved the administration
      of single antioxidant nutrients given at relatively high doses. The results of
      trials investigating the effect of a balanced combination of antioxidants at
      levels achievable by diet are awaited. CONCLUSION: The suggestion that
      antioxidant supplements can prevent chronic diseases has not been proved or
      consistently supported by the findings of published intervention trials. Further
      evidence regarding the efficacy, safety and appropriate dosage of antioxidants in
      relation to chronic disease is needed. The most prudent public health advice
      remains to increase the consumption of plant foods, as such dietary patterns are
      associated with reduced risk of chronic disease.

PMID- 15153273
TI  - Factors to consider in Micronesian food-based interventions: a case study of
      preventing vitamin A deficiency.
AB  - BACKGROUND: Many factors need to be considered in a food-based intervention.
      Vitamin A deficiency and chronic diseases, such as diabetes, heart disease and
      cancer, have become serious problems in the Federated States of Micronesia (FSM)
      following the decreased production and consumption of locally grown foods.
      However, agricultural and social conditions are still favourable for local food
      production. AIM: To identify key factors to consider in a Micronesian food-based
      intervention focusing on increased production and consumption of four major
      Micronesian staple foods: banana, breadfruit, giant swamp taro and pandanus.
      METHODS: Ethnographic methods including key informant interviews and a literature
      review. RESULTS: Pacific and Micronesian values, concepts of food and disease,
      and food classifications differ sharply from Western concepts. There are few FSM
      professionals with nutrition expertise. Traditional foods and food cultivars vary
      in nutrient content, consumption level, cost, availability, status, convenience
      in growing, storing and cooking, and organoleptic factors. CONCLUSIONS: A
      systematic consideration of the factors that relate to a food-based intervention
      is critical to its success. The evaluation of which food and cultivar of that
      food that might be most effectively promoted is also critical. Regional
      differences, for example FSM inter-island differences between the staple foods
      and cultivars, must be considered carefully. The evaluation framework presented
      here may be relevant to Pacific Island and other countries with similar foods
      where food-based interventions are being planned. An ethnographic approach was
      found to be essential in understanding the cultural context and in data
      collection and analysis.

PMID- 15153274
TI  - How feasible are healthy eating and physical activity for young women?
AB  - OBJECTIVE: This study investigated young women's perceptions of the feasibility
      of physical activity and healthy eating behaviours, and how these vary by socio
      economic status, domestic characteristics and weight status. DESIGN: This
      population-based study used a mailed questionnaire to investigate perceptions of
      the feasibility of commonly recommended healthy eating and physical activity
      behaviours among a sample of young women. The feasibility of 29 physical activity
      behaviours (e.g. relating to frequency, intensity, duration, domain/setting) and
      15 healthy eating behaviours (e.g. relating to location/setting, fruit and
      vegetable intake, fat/sugar intake) was assessed. Height, weight and
      sociodemographic details were also obtained. SETTING: Nation-wide community-based
      survey. SUBJECTS: A total of 445 women aged 18-32 years selected randomly from
      the Australian electoral roll. RESULTS: Most women reported that they either were
      already engaged in many of the healthy eating behaviours or saw these as highly
      feasible. Many physical activity behaviours, on the other hand, were perceived as
      less feasible, particularly among women with children and women who were
      overweight. CONCLUSIONS: Health promotion messages and strategies aimed at
      increasing physical activity and healthy eating are unlikely to succeed unless
      they take into account perceptions that these behaviours are not feasible. For
      young women, this may involve promoting more time-effective, flexible ways of
      achieving recommended physical activity. Messages specifically targeted to women
      with children, and women who are overweight, are required.

PMID- 15153275
TI  - How well do Australian women comply with dietary guidelines?
AB  - OBJECTIVE: To investigate the proportion of middle-aged Australian women meeting
      national dietary recommendations and its variation according to selected
      sociodemographic and behavioural characteristics. DESIGN: This cross-sectional
      population-based study used a food-frequency questionnaire to investigate dietary
      patterns and compliance with 13 commonly promoted dietary guidelines among a
      cohort of middle-aged women participating in the Australian Longitudinal Study on
      Women's Health. SETTING: Nation-wide community-based survey. SUBJECTS: A total of
      10,561 women aged 50-55 years at the time of the survey in 2001. RESULTS: Only
      about one-third of women complied with more than half of the guidelines, and only
      two women in the entire sample met all 13 guidelines examined. While guidelines
      for meat/fish/poultry/eggs/nuts/legumes and 'extra' foods (e.g. ice cream,
      chocolate, cakes, potatoes, pizza, hamburgers and wine) were met well, large
      percentages of women (68-88%) did not meet guidelines relating to the consumption
      of breads, cereal-based foods and dairy products, and intakes of total and
      saturated fat and iron. Women working in lower socio-economic status occupations,
      and women living alone or with people other than a partner and/or children, were
      at significantly increased risk of not meeting guidelines. CONCLUSIONS: The
      present results indicate that a large proportion of middle-aged Australian women
      are not meeting dietary guidelines. Without substantial changes in their diets,
      and help in making these changes, current national guidelines appear unachievable
      for many women.

PMID- 15153277
TI  - Prevalence of overweight and obesity among young people in Great Britain.
AB  - OBJECTIVE: To determine the prevalence of overweight and obesity in British young
      people (4-18 years) in 1997. DESIGN: Cross-sectional analysis of the National
      Diet and Nutrition Survey of young people. SETTING: Great Britain. SUBJECTS:
      Nationally representative sample of 1836 young people (age 4-18 years). RESULTS:
      The prevalence of obesity based on body mass index (weight/height(2)) and the
      International Obesity Task Force cut-offs was 4.0%, with a further 15.4%
      identified as overweight. Asians were almost four times as likely to be obese as
      white subjects (13.6 vs. 3.5%, P<0.001). Among white subjects there was no
      significant difference in the prevalence of obesity between girls and boys, or
      with age. The risk of obesity was significantly higher in subjects from social
      classes IV and V than from social classes I-III (6.5 vs. 2.7%, P=0.003). Subjects
      living in Scotland and Wales were significantly more likely to be obese than
      those in England (7.6 and 6.5 vs. 2.9%, respectively, P<0.01). Multiple logistic
      regression showed that, among white subjects, those in social classes IV and V
      living in Wales and Scotland were three times more likely to be obese than the
      other children in the survey (odds ratio 3.3, 95% confidence interval 1.1-9.8).
      CONCLUSION: These data provide information on the national prevalence of
      overweight and obesity in Great Britain and baseline data from which to monitor
      future trends. This analysis provides important demographic information on those
      most at risk of obesity, which may be used to inform public health strategies to
      prevent obesity in young people.

PMID- 15153276
TI  - Large heterogeneity of the obesity epidemic in Danish adults.
AB  - OBJECTIVE: To examine to what extent the obesity epidemic is a general phenomenon
      in adults by assessing the secular change, by birth cohort and age, in the
      prevalence of obesity and median body mass index (BMI) in Danish men and women
      measured between 1964 and 1994. DESIGN: Multiple cross-sectional population
      surveys. SETTING: The greater Copenhagen area of Denmark. SUBJECTS: The study
      included 17,065 men (30 336 observations) and 13,417 women (24,065 observations),
      aged 20-84 years. MAIN OUTCOME MEASURES: Trends in median BMI and prevalence of
      obesity estimated from measured height and weight in 10-year age groups. RESULTS:
      In general the prevalence of obesity was increasing, although in an irregular
      way: among men in two phases, during the 1970s and 1990s and among women only
      during the 1990s. Great heterogeneity was observed between birth cohorts and age
      groups. There was only little indication of an increasing trend in obesity
      prevalence for women, except for the 55-64-year-olds. In men, the prevalence of
      obesity was increasing in all age groups except in the youngest ones, and it was
      statistically significant only for men aged 35-74 years. There was no significant
      linear change in median BMI in any group, except for an increasing trend among
      men aged 50 years and above. CONCLUSION: Although the overall Danish trend for
      obesity prevalence, similar to trends world-wide, showed a marked increase, the
      trend was very heterogeneous and generally neither uniform nor significantly
      positive; the changes were irregular, different among men and women, and
      different in the different age and birth cohorts. The obesity problem in middle
      aged and older men of certain birth cohorts poses a specific public health
      challenge. Future studies of determinants behind the heterogeneity in the
      development of the obesity epidemic may provide clues to its causes.

PMID- 15153278
TI  - Homocysteine and cobalamin status in German vegans.
AB  - OBJECTIVE: The study aimed to evaluate the homocysteine and cobalamin status of
      German vegans and determine whether the intake of very small amounts of foods of
      animal origin can improve this status. DESIGN AND SETTING: Cross-sectional study,
      Germany. SUBJECTS: The dietary and nutritional intakes of 131 vegans (73 women,
      58 men; age range: 20.2-82.1 years) were evaluated using a general questionnaire
      and two food-frequency questionnaires. RESULTS: The prevalence of inadequate
      cobalamin status in volunteers of the German Vegan Study was 28.2%, and that of
      hyperhomocysteinaemia, 38.1%. Moderate vegans were affected to a lesser extent
      than were strict vegans. Duration of veganism and cobalamin concentration were
      inversely correlated (Spearman's r=-0.175, P=0.047). Folate concentration and
      erythrocyte aspartic acid aminotransferase activity were not correlated with
      plasma homocysteine concentration, but duration of veganism correlated positively
      with homocysteine concentration (Spearman's r=0.319, P<0.001). Cobalamin and
      homocysteine concentrations were inversely correlated (when controlling for
      duration of veganism; r=-0.602, P<0.001). CONCLUSION: Cobalamin status needs to
      be improved in order to minimise the risk of hyperhomocysteinaemia.

PMID- 15153279
TI  - Partial purification and characterization of Gigantocotyle explanatum somatic
      antigens.
AB  - Soluble extracts of Gigantocotyle explanatum, isolated from the liver of buffalo
      Bubalus bubalis were fractionated on Sephadex G-200 columns. Nine major fractions
      referred to as F1, F2, F3, F4, F5, F6, F7, F8 and F9 were separated. Each
      fraction was tested by ELISA for antigenicity using sera from G. explanatum
      infected field buffaloes. Fractions F1 and F2 were highly antigenic, F3, F4, F6
      and F7 were moderately antigenic and F5, F8 and F9 were poorly antigenic.
      Analyses by SDS-PAGE revealed that each fraction comprised several polypeptide(s)
      in the molecular weight range of <29 to >205 kDa. Results of Western blotting
      indicated that not all polypeptides which appeared in the SDS-PAGE were
      antigenic. The antigenic molecules of each fraction were mostly in the low
      molecular weight range of <14 to >94 kDa with the polypeptides in the range of
      >14, 14, 18, 21-25 and 34-36 kDa.

PMID- 15153280
TI  - The influence of climate on the distribution of monogeneans of anurans in
      Nigeria.
AB  - Investigations undertaken on the monogeneans of amphibians in Nigeria have shown
      that host ecology has an influence on the distribution of these monogeneans.
      Amphibians from humid environments of the rainforest, a freshwater swamp and
      mangrove harboured no monogeneans, whereas those occurring in drier conditions in
      the savannah-mosaic and guinea savannah yielded five species of polystomatid
      parasites: Polystoma prudhoei from Bufo regularis, Polystoma galamensis from Rana
      galamensis, Eupolystoma alluaudi from Bufo regularis and Bufo maculatus, and two
      unidentified Polystoma species from Bufo regularis and Ptychadena oxyrynchus,
      respectively. Some of these monogeneans appear to have reproduction cycles which
      are synchronized with those of the hosts. The prevalence of E. alluaudi in Bufo
      spp. caught in New Bussa (68.4% in B. regularis and 82.3% in B. maculatus) were
      higher than those reported for this parasite in other locations in West Africa
      and for Eupolystoma anterorchis in Bufo pardalis from the Cape Flats of South
      Africa.

PMID- 15153281
TI  - Goezia bangladeshi n. sp. (Nematoda: Anisakidae) from an anadromous fish
      Tenualosa ilisha (Clupeidae).
AB  - A total of 1432 hilsa shad, Tenualosa ilisha (=Hilsa ilisha) from 11 fresh water,
      brackish water and marine localities in Bangladesh yielded 13 adult Goezia
      bangladeshi n. sp., all specimens being found in the intestine of a single fish
      host caught in the lower Ganges. A total of 2372 Goezia juveniles were recovered
      from 490 infected fish (prevalence 34.2%). This is the first Goezia species
      recorded from Bangladesh, and it differs from other valid species by the number
      of caudal papillae (pre 7-9, para 3, post 6); encircled by tiny spines, the
      position of double papillae, the arrangement of body spines, and the length ratio
      of the intestinal caecum and the ventricular appendix (1: 3.33-4.72). Juveniles
      were free in the gut, embedded in the gut wall and encapsulated in mesenteries.
      Tenualosa ilisha serves as the definitive host, but the predominance of juveniles
      may indicate that piscivorous hosts may also serve as such. A list of the nominal
      Goezia species with important characters is provided.

PMID- 15153282
TI  - Fasciola hepatica: cercarial productivity of redial generations in long-surviving
      Galba truncatula.
AB  - Bimiracidial infections of Galba truncatula with Fasciola hepatica were carried
      out to determine the effect of food quality on the frequency of 1- and 2
      sporocyst infections, to analyse its impact on the developmental patterns
      (normal, or abnormal) of redial generations, and to verify its consequences on
      cercarial production. These investigations were performed in snails reared at 20
      degrees C and provided with cos lettuce and commercial fish food (Tetraphyll) as
      a food source until their death. Double-sporocyst infections with normal
      development of redial generations were recorded in 43.9% of infected snails (out
      of 296). Single-sporocyst infections were noted in the other snails, with normal
      development of generations in 53.7% and abnormal development (the first mother
      redia early degenerated) in 2.4%. Four successive redial generations were found
      in long-surviving snails (more than 90 days). In both 1- and 2-sporocyst
      infections, showing normal development of generations, the daughter rediae, which
      exited from the first mother redia (R2a rediae), constituted the greater group of
      free rediae and produced the highest percentages of cercariae (46.2-48.2%).
      However, the development of these rediae inside the snail body was slower in 2
      sporocyst infections than in 1-sporocyst infections. The numbers of rediae noted
      in subsequent generations (R2b/R3a and R3b/R4a rediae) were similar, whatever the
      number of full-grown sporocysts. The number of shed cercariae recorded in the 1-
      and 2-sporocyst infections did not significantly differ. When long-surviving
      snails died, 19.8-20.7% of cercariae produced by free rediae (essentially by
      R2b/R3a and R3b/R4a rediae) were still present in their bodies. The increased
      frequency of 2-sporocyst infections demonstrated that food quality had a
      significant effect on the redial burden of F. hepatica developing inside G.
      truncatula.

PMID- 15153283
TI  - Density-dependent effects on the survival and growth of the rodent stomach worm
      Protospirura muricola in laboratory mice.
AB  - The spirurid nematode, Protospirura muricola, is of intrinsic interest as a
      rodent model of gastric nematode infections. Since worm burdens can be very heavy
      in nature, density dependent processes may constrain parasite growth. Laboratory
      mice (BKW) were exposed to varying doses of infective larvae of P. muricola in
      the range 5 to 40 third-stage larvae (L3), in four separate experiments in which
      progressively higher doses were utilized. All mice were culled 60 days after
      infection and a total of 518 worms (226 male and 292 female worms) was recovered,
      measured and weighed. Overall survival was 58.9%, but survival declined
      significantly with increasing dose by approximately 21% (from 66% at 5 L3 per
      mouse to 52% at 40 L3 per mouse). The length and weight of worms correlated
      positively in both sexes. Total worm biomass increased linearly with increasing
      numbers of worms. However, whilst the length and weight of male worms declined
      with increasing worm burden (8.4 and 24.6% respectively), female worms were less
      affected, only length showing a significant reduction with increasing parasite
      burden (16.0%). Therefore, increasing worm burdens impeded growth of P. muricola,
      but reduction in length and weight were relatively small in relation to the
      overall size of this nematode. Increasing worm burdens were associated with loss
      of host weight and reduction in stomach weight and worm burdens in excess of 20
      exerted a measurable cost to the host, which in the field, may be associated with
      loss of overall host fitness.

PMID- 15153284
TI  - The role of Bithynia tentaculata in the transmission of larval digeneans from a
      gravel pit in the Lower Thames Valley.
AB  - The freshwater snail, Bithynia tentaculata (Gastropoda: Prosobranchia), is
      frequently found in gravel pits and its role in the transmission of larval
      digeneans was assessed in one of these unstable water bodies from the Lower
      Thames Valley (UK) from June 1982 to December 1984. Eight species of cercarial
      and five species of metacercarial infections were reported from B. tentaculata,
      with up to 7.7% and 4.7% prevalence of infections, respectively, occurring in the
      snail, making it the most important host at this site. Seasonal peaks in
      cercarial infections occurred in late autumn/early winter but little seasonality
      was apparent in the occurrence of metacercarial infections. The life history
      characteristics of both hosts and parasites, which can affect intramolluscan
      digenean dynamics, are discussed.

PMID- 15153285
TI  - Comparative methodology for the detection and differentiation of circulating
      microfilariae of Dirofilaria immitis in the dog.
AB  - The sensitivities of the Knott's test (four 20-microl sediment aliquots),
      quantitative buffy coat capillary tube method (QBC tube, 111 microl of whole
      blood) and direct blood smear (DBS, 20 microl of whole blood) were evaluated for
      the detection of microfilaraemia in dogs. Undiluted whole blood samples taken
      from 70 Dirofilaria immitis antigen-positive dogs and 10 serially diluted
      microfilaraemic blood samples at concentrations of 400, 200, 100, 50, 25 and 12
      microfilariae (mff) ml(-1) were examined. For filarial speciation, the buffy coat
      of QBC tubes was mixed with one drop of methylene blue-formalin solution and
      examined as a direct smear. In 52/70 microfilaraemic blood samples, the number of
      mff ranged from 12 to 321987 ml(-1) (median: 3199 ml(-1)). The diagnostic
      sensitivity of the Knott's test, QBC tube method and DBS in undiluted blood
      samples attained the 100%, 98% and 92.3% levels, respectively. Eighteen dogs
      tested amicrofilaraemic by all three methods. At concentrations of 400 mff ml(
      1), a 100% sensitivity was found by all three methods, while at 200 mff ml(-1)
      the Knott's test, QBC tube and DBS were 100%, 100% and 90% sensitive,
      respectively. The relevant figures at 100 mff ml(-1) were 100%, 100% and 80%, at
      50 mff ml(-1) 100%, 100% and 50%, at 25 mff ml(-1) 100%, 100% and 10% and at 12
      mff ml(-1) 80%, 50% and 10%. At 50 and 25 mff ml(-1), the DBS was less sensitive
      compared to the other two methods, while at 12 mff ml(-1), only to the Knott's
      test. A significant correlation was found between the QBC tube method and Knott's
      test regarding mff speciation. Therefore, the QBC method may be considered a
      reliable alternative to the Knott's test for both the detection and speciation of
      mff in the dog.

PMID- 15153286
TI  - Patterns of infracommunity species richness in eels, Anguilla anguilla.
AB  - Between October 1999 and October 2001, a total of 510 European eels Anguilla
      anguilla were captured in 13 different samples from the rivers Thames (five
      locations) and Test (one location) in southern England. The relationship between
      parasite component community species richness (CCR) and maximum infracommunity
      species richness (ICRmax) compared with that previously observed in bird and
      mammal hosts. Specifically, the maximum number of parasite species occurring in
      infracommunities equalled or exceeded half the number of parasite species in the
      component community at that time, across a wide range of CCR values (2-9 parasite
      species). Furthermore, the frequency distribution of infracommunity richness
      (ICR) suggested that the species composition of infracommunities is probably
      random. These findings suggest that intestinal macroparasite infracommunities in
      eels are unsaturated and potentially species rich assemblages and, in these
      respects, share a fundamental similarity with the infracommunities of birds and
      mammals.

PMID- 15153287
TI  - An ultrastructural study of the cercarial excretory system in Bucephaloides
      gracilescens and Prosorhynchus squamatus.
AB  - The ultrastructure of the flame cells, capillaries, collecting tubes, excretory
      bladder, excretory atrium, caudal vesicle, lateral caudal ducts and excretory
      pores of cercariae of Bucephaloides gracilescens (Rudolphi, 1819) Hopkins, 1954
      and Prosorhynchus squamatus Odhner, 1905 (Digenea: Bucephalidae) is described.
      Both species are essentially similar except for some details. The terminal parts
      of the protonephridia have all the structural features that are typical of
      trematodes. The collecting tubes in the cercarial body are composed of cells that
      are wrapped around the lumen. The main collecting tubes are joined to the
      excretory bladder syncytium by septate junctions. Features of P. squamatus
      excretory bladder epithelium indicate that it is involved in secretory activity,
      but this is not the case in B. gracilescens. In both species the luminal surface
      of the excretory bladder epithelium is increased by lamellae, and the basal
      plasma membrane forms invaginations. In the bladder syncytium of P. squamatus
      both apical lamellae and basal invaginations are more developed and mitochondria
      are also more numerous. The excretory atrium is lined by a syncytium with
      nucleated cytons located in the surrounding parenchyma. The atrium lining is not
      continuous with the body tegument and possesses specific secretory inclusions and
      a thick glycocalyx. Septate junctions connect the atrium syncytium to the
      excretory bladder epithelium at its anterior end and to the syncytial excretory
      epithelium lining the caudal vesicle and the lateral caudal ducts at its
      posterior. In the excretory pores the caudal duct syncytium is joined to the
      tegument by septate desmosomes.

PMID- 15153288
TI  - Evaluation by the skin prick test of Anisakis simplex antigen purified by
      affinity chromatography in patients clinically diagnosed with Anisakis
      sensitization.
AB  - Anisakis simplex crude extracts (CE) (IPI, ASAC and ALK-ABELLO), A. simplex
      larval antigens purified using a column of IgG anti-A. simplex (PAK) or a column
      of IgG anti-Ascaris suum (PAS), antigen eluted from columns of IgG anti-A. suum
      (EAS) and an A. suum adult CE were assayed by the skin prick test. Thirty percent
      of assayed patients showed a negative reaction in the Anisakis skin prick test.
      Of 70% positives, two patients had a weal greater than that produced by histamine
      with the A. simplex extract from ABELLO and IPI. The A. suum skin prick test was
      positive in 35% of patients, with a lower reaction than that observed with the A.
      simplex extract from IPI in 57% of the sera and a higher reaction in 28% of the
      sera. All patients with positive reactions with the crude extract also showed
      positive weals with the two purified antigens, PAK and PAS. All patients, except
      three, with a reaction to A. suum antigen, were positive to the EAS antigen. In
      five patients the weal size produced by PAS was greater than that observed with
      PAK, whereas in another six patients the contrary was observed. Only one of these
      six patients did not react to EAS antigen, coincident with the patient showing
      only a slight increase (7%) in the weal size induced by PAK vs. PAS. When the EAS
      antigen was tested on patients positive to both PAK and PAS, six patients
      presented a weal size of >30% and only three patients who were positive to PAS
      did not react to the EAS antigen. These three patients were also negative against
      the A. suum CE. Purification by affinity chromatography eliminates from the PAS
      antigen the proteins responsible for producing cross-reactions with Ascaris
      (present in the EAS antigen).

PMID- 15153289
TI  - Histopathological changes during experimental infections of calves with Cooperia
      punctata.
AB  - Eleven male two-month-old Holstein calves were used to determine the pathological
      changes induced by a Cooperia punctata infection. After weaning, ten calves
      received a single oral dose of 45,000 C. punctata infective larvae. One calf
      remained as a non-infected control. Groups of two calves were killed on days 7,
      14, 21, 28 and 35 post-infection (p.i.) for determination of worm burdens and
      histopathological evaluation. The small intestine was sub-divided into three
      sections of approximately equal length, and representative samples of mucosa were
      fixed in 10% formalin, cut, and stained with haematoxylin-eosin. Samples of
      intestinal contents and mucosal digests were taken and fixed in 10% formalin for
      an estimation of total worm burdens. An increase in the number of adult parasites
      and a decrease in the number of larvae were observed with time (P<0.001). A
      higher concentration of worms was found in the first segment of the small
      intestine during the five weeks of observation. Histology showed larvae in the
      intestinal mucosa on day 7 p.i., with a discrete increase in the cellular
      response. Adult worms and a marked cellular infiltrate with eosinophils and
      neutrophils were present on day 21 p.i., and these persisted until day 35 p.i.
      Microcysts resulting from worm destruction were observed from day 21 p.i.

PMID- 15153290
TI  - Fasciola hepatica and Paramphistomum daubneyi: field observations on the
      transport and outcome of floating metacercariae in running water.
AB  - Experimental investigations in eight open drainage ditches and furrows from
      central France were carried out to analyse the dispersal of floating
      metacercariae of two digenean species by running water and to determine the
      outcome of larvae which settled on Nasturtium officinale (watercress). The
      frequencies of larvae found after their transport by water ranged from 33% to
      49.7%, thus indicating that more than half of the metacercariae used in this
      experiment had fallen to the bottom of the water during this transport. The
      nature of the site (furrow, or ditch supplied by a spring) had a significant
      effect on the distribution of floating larvae, while the digenean species had no
      effect. Low percentages of metacercariae on watercress were noted in furrows (3.5
      4.3% of larvae) and ditches (0.8-1.3%). When the watercress grew, most larvae
      that had settled on leaves and stems died but there were always several living
      metacercariae on this plant (0.7-1.5% of larvae for Fasciola hepatica and 0.2
      0.5% for Paramphistomum daubneyi). The weak buoyancy of these floating cysts on
      running water limited their dispersal and, consequently, led to a real diminution
      of risks incurred by definitive hosts towards these metacercariae.

PMID- 15153291
TI  - Epidemiology of Ancylostoma spp. in the endangered Iberian lynx (Lynx pardinus)
      in the Donana National Park, south-west Spain.
AB  - The epidemiology of Ancylostoma spp. was studied in the endangered Iberian lynx
      (Lynx pardinus) in the Donana National Park, south-west Spain. Faecal samples
      were collected throughout a complete annual cycle (August 1997 to September
      1998). The overall egg prevalence of Ancylostoma spp. was 57.8%. The pattern of
      abundance of Ancylostoma spp. eggs in faeces was overdispersed. Juvenile lynx
      demonstrated a statistically higher prevalence and abundance of Ancylostoma spp.
      than in adults. These levels of egg output (maximum 21195 epg), as previously
      reported in free ranging large felid cubs, could be close to disease involvement.
      The potential pathogenicity of hookworms and the influence of individual and
      ecological factors on hookworm transmission in the Iberian lynx from the Donana
      National Park population are discussed.

PMID- 15153292
TI  - Effects of glucose on survival, infectivity and linear movement of the cercariae
      of Echinostoma caproni.
AB  - The effects of glucose in artificial spring water (ASW) on the survival,
      infectivity, and linear movement of Echinostoma caproni cercariae were studied.
      Cercariae maintained at 23 degrees C in 1% glucose in ASW (ASWG) or ASW alone,
      reached 50% survival at 26 and 23 h, respectively. All cercariae in ASWG and ASW
      were dead by 50 and 32 h, respectively. Infectivity to juvenile Helisoma
      trivolvis (Colorado strain) snails was significantly less for cercariae aged 16 h
      in ASWG compared to cercariae aged 16 h in ASW. Linear movement, i.e. the ability
      of cercariae to traverse a 1-cm radius, ceased at 16 and 20 h for cercariae
      maintained in ASWG and ASW, respectively. Glucose added to ASW extended the
      survival time of E. caproni cercariae but decreased their ability to infect
      snails or move in a linear direction.

PMID- 15153293
TI  - Recent advances in transgenic arthropod technology.
AB  - The ability to insert foreign genes into arthropod genomes has led to a diverse
      set of potential applications for transgenic arthropods, many of which are
      designed to advance public health or improve agricultural production. New
      techniques for expressing foreign genes in arthropods have now been successfully
      used in at least 18 different genera. However, advances in field biology are
      lagging far behind those in the laboratory, and considerable work is needed
      before deployment in nature can be a reality. A mechanism to drive the gene of
      interest though a natural population must be developed and thoroughly evaluated
      before any field release, but progress in this area has been limited. Likewise,
      serious consideration of potential risks associated with deployment in nature has
      been lacking. This review gives an overview of the most promising techniques for
      expressing foreign genes in arthropods, considers the potential risks associated
      with their deployment, and highlights the areas of research that are most
      urgently needed for the field to advance out of the laboratory and into practice.

PMID- 15153294
TI  - Arthropod community structure in pastures of an island archipelago (Azores):
      looking for local-regional species richness patterns at fine-scales.
AB  - The arthropod species richness of pastures in three Azorean islands was used to
      examine the relationship between local and regional species richness over two
      years. Two groups of arthropods, spiders and sucking insects, representing two
      functionally different but common groups of pasture invertebrates were
      investigated. The local-regional species richness relationship was assessed over
      relatively fine scales: quadrats (= local scale) and within pastures (= regional
      scale). Mean plot species richness was used as a measure of local species
      richness (= alpha diversity) and regional species richness was estimated at the
      pasture level (= gamma diversity) with the 'first-order-Jackknife' estimator.
      Three related issues were addressed: (i). the role of estimated regional species
      richness and variables operating at the local scale (vegetation structure and
      diversity) in determining local species richness; (ii). quantification of the
      relative contributions of alpha and beta diversity to regional diversity using
      additive partitioning; and (iii). the occurrence of consistent patterns in
      different years by analysing independently between-year data. Species assemblages
      of spiders were saturated at the local scale (similar local species richness and
      increasing beta-diversity in richer regions) and were more dependent on
      vegetational structure than regional species richness. Sucking insect herbivores,
      by contrast, exhibited a linear relationship between local and regional species
      richness, consistent with the proportional sampling model. The patterns were
      consistent between years. These results imply that for spiders local processes
      are important, with assemblages in a particular patch being constrained by
      habitat structure. In contrast, for sucking insects, local processes may be
      insignificant in structuring communities.

PMID- 15153295
TI  - An aerial netting study of insects migrating at high altitude over England.
AB  - Day and night sampling of windborne arthropods at a height of 200 m above ground
      was undertaken at Cardington, Bedfordshire, UK, during July 1999, 2000 and 2002,
      using a net supported by a tethered balloon. The results from this study are
      compared with those from the classic aerial sampling programmes carried out by
      Hardy, Freeman and colleagues over the UK and North Sea in the 1930s. In the
      present study, aerial netting was undertaken at night as well as daytime, and so
      the diel periodicity of migration could be investigated, and comparisons made
      with the results from Lewis and Taylor's extensive survey of flight periodicity
      near ground level. In some taxa with day-time emigration, quite large populations
      could continue in high-altitude flight after dark, perhaps to a previously
      underrated extent, and this would greatly increase their potential migratory
      range. Any trend towards increases in night temperatures, associated with global
      warming, would facilitate movements of this type in the UK. Observations on the
      windborne migration of a variety of species, particularly those of economic
      significance or of radar-detectable size, are briefly discussed.

PMID- 15153296
TI  - Effects of age and food source on secondary chemistry of larvae of Lymantria
      species (Lepidoptera: Lymantriidae).
AB  - Haemolymph and osmeterial secretions of caterpillars of Lymantria monacha
      (Linnaeus) and L. concolor Walker were analysed by gas chromatography/mass
      spectrometry for low molecular weight secondary metabolites. The similarities of
      their chemical compositions were determined by means of cluster analysis
      techniques in order to characterize possible chemical variations related to
      developmental stage or food of the larvae. For this purpose, two dissimilarity
      coefficients (Euclidean distances, Canberra metrics) and four clustering methods
      (UPGMA, WPGMA, WPGMC, single linkage) were combined. The patterns of secondary
      compounds obtained from the haemolymph and osmeterial secretions studied did not
      differ statistically significantly between two groups of L. monacha larvae fed
      with either larch, Larix decidua Mil., or Norway spruce, Picea abies (L.),
      indicating no relevant influence of plant chemistry. However, haemolymph of
      penultimate instar larvae of L. concolor fed on Rhododendron contained a mixture
      of compounds differing statistically significantly from that of last instar
      caterpillars. The total compositions of the corresponding gland secretions were
      statistically identical though the presence/amounts of individual compounds
      varied. This suggested that the haemolymph composition reflected changing
      physiological requirements of the successive instars, whereas the composition of
      the defensive mixtures remained comparatively constant, possibly due to a
      constant spectrum of potential enemies. A more pronounced age-dependence of
      larval chemistry was shown by a similar analysis of data from various
      developmental stages of L. dispar (Linnaeus) and one of its food plants. This
      analysis suggested plant composition affected the secondary chemistry of early
      larval instars of L. dispar. The results are discussed in terms of the roles of
      secondary metabolites in defence against natural enemies.

PMID- 15153297
TI  - Nectar-related vs. human-related volatiles: behavioural response and choice by
      female and male Anopheles gambiae (Diptera: Culicidae) between emergence and
      first feeding.
AB  - The close association of Anopheles gambiae Giles with humans and its females'
      ability to live on human blood alone suggest that females may ignore sources of
      sugar in favour of human blood as a source of energy. They have limited energy
      reserves at emergence, and at 27 degrees C both sexes generally die if they do
      not feed during night 1, 24-36 h after emergence. Food preferences during this
      critical period were tested by measuring responses to volatiles from honey and
      soiled socks, which served as surrogates for nectar-related and human-related
      volatiles in a wind-tunnel olfactometer. Both sexes responded more strongly to
      honey than to human volatiles, and given a choice, preferred honey over human
      volatiles. After 5 days of sugar access and maturation, males continued to prefer
      honey volatiles, whereas females changed behaviour, responding almost exclusively
      to human volatiles. Night 1 experiments also demonstrated that: (i). females
      previously having had sugar during the night of emergence responded more strongly
      to human volatiles; (ii). large-bodied mosquitoes of both sexes responded more
      strongly to honey than small-bodied ones; and (iii). females were equally
      responsive to honey in both early and late scotophase but were slightly more
      responsive to human volatiles in late scotophase. These results indicate that for
      a female's first meal, sugar is a viable option and is preferred when nectar
      related stimuli are strong. This supports field evidence that sugar-feeding is a
      significant component of A. gambiae female behaviour.

PMID- 15153298
TI  - Biological control of sciarid and phorid pests of mushroom with predatory mites
      from the genus Hypoaspis(Acari: Hypoaspidae) and the entomopathogenic nematode
      Steinernema feltiae.
AB  - In small-scale experiments, the predatory mites, Hypoaspis aculeifer (Canestrini)
      and H. miles Berlese, applied at 700 mites m(-2), and the entomopathogenic
      nematode, Steinernema feltiae (Filipjev) applied at 3 x 10(-6) nematodes m(-2)
      controlled sciarids and phorids in mushroom compost and casing substrates. For
      both mite species, earliest application to the growing substrate following
      sciarid infestation reduced sciarid emergence. In contrast, later application of
      each biological control agent provided more effective control of phorid
      emergence. The behaviour of adult mites suggested that H. aculeifer were more
      positively geotactic than H. miles although both species could penetrate compost
      and casing substrates to a depth of 2-12 cm. A majority of S. feltiae nematodes
      resided at a depth of 2-4 cm in both substrate types. Independent application of
      H. aculeifer provided more comprehensive control of sciarids and phorids than the
      other biological agents studied, owing to its better dispersal within compost and
      casing, and ability to attack larvae of differing ages.

PMID- 15153299
TI  - Lack of intraspecific biological variation between two geographical populations
      of Oomyzus sokolowskii (Hymenoptera: Eulophidae), a gregarious larval-pupal
      parasitioid of Plutella xylostella (Lepidoptera: Plutellidae).
AB  - The chalcid, Oomyzus sokolowskii Kurdjumov has been recorded in many parts of the
      world as a major larval-pupal, gregarious endoparasitoid of the diamondback moth,
      Plutella xylostella (Linnaeus), a serious pest of brassica vegetable crops
      worldwide. This study investigated intraspecific variation between two
      populations of O. sokiolowskii, one from Cape Verde Islands, West Africa and the
      other from Hangzhou, China. In all crosses and backcrosses between the two
      geographical populations, the numbers of progeny and sex ratio of progeny were
      similar to those obtained within each of the populations, demonstrating complete
      reproductive compatibility between the two populations. The two populations
      showed similar responses to temperature with respect to development time and
      survival of immature stages. Observations on the interactions between the two O.
      sokolowskii populations and Cotesia plutellae (Kurdjumov), another major
      parasitoid of P. xylostella, showed that neither population could achieve
      successful parasitism of P. xylostella larvae already parasitized by C.
      plutellae. However, both O. sokolowskii populations could achieve hyperparasitism
      by ovipositing into a mid-late stage larva of C. plutellae developing inside the
      primary host. Contrary to earlier reports, no evidence of intraspecific
      variations in ability to hyperparasitize between these two populations of O.
      sokolowskii was found.

PMID- 15153301
TI  - Building successful biological databases.

PMID- 15153300
TI  - An interspersed refuge for Sitodiplosis mosellana (Diptera: Cecidomyiidae) and a
      biocontrol agent Macroglenes penetrans (Hymenoptera: Pteromalidae) to manage crop
      resistance in wheat.
AB  - An interspersed refuge of susceptible plants in a resistant, spring-sown wheat
      crop was tested as a strategy to protect crop resistance against evolution of
      virulence by the wheat midge Sitodiplosis mosellana (Gehin), and also to conserve
      a biocontrol agent Macroglenes penetrans(Kirby). Eight replicated field
      experiments were conducted using seed mixtures of 0, 5, 10, 15 and 100% or 0, 5
      and 100% susceptible wheat with an agronomically similar wheat expressing the
      antibiotic resistance gene Sm1. The frequencies of eggs, mature larvae and
      parasitized larvae in susceptible and resistant wheat spikes, and midge-affected
      seeds in the harvest, were recorded for each plot. In susceptible wheat, insect
      densities and seed damage were typical of those in commercial wheat. In resistant
      wheat, few larvae completed development, 2% or less compared with about 80% in
      susceptible wheat, when larvae were sampled at maturity. This resistant wheat
      also deterred midge oviposition, reducing egg densities by 65% compared with
      susceptible wheat. The wheat midge and its parasitoid oviposited throughout the
      plots, and parasitism was density independent. The densities of mature midge
      larvae and parasitoids were in proportion to the size of the refuge. A 5%
      susceptible refuge produced about 41 mature larvae for each mature larva from the
      resistant wheat, and provided effective control of damage. An interspersed refuge
      of susceptible plants in resistant wheat is a promising strategy for sustaining
      resistance conferred by Sm1 and biocontrol of the wheat midge.

PMID- 15153302
TI  - Saccharomyces genome database: underlying principles and organisation.
AB  - A scientific database can be a powerful tool for biologists in an era where large
      scale genomic analysis, combined with smaller-scale scientific results, provides
      new insights into the roles of genes and their products in the cell. However, the
      collection and assimilation of data is, in itself, not enough to make a database
      useful. The data must be incorporated into the database and presented to the user
      in an intuitive and biologically significant manner. Most importantly, this
      presentation must be driven by the user's point of view; that is, from a
      biological perspective. The success of a scientific database can therefore be
      measured by the response of its users - statistically, by usage numbers and, in a
      less quantifiable way, by its relationship with the community it serves and its
      ability to serve as a model for similar projects. Since its inception ten years
      ago, the Saccharomyces Genome Database (SGD) has seen a dramatic increase in its
      usage, has developed and maintained a positive working relationship with the
      yeast research community, and has served as a template for at least one other
      database. The success of SGD, as measured by these criteria, is due in large part
      to philosophies that have guided its mission and organisation since it was
      established in 1993. This paper aims to detail these philosophies and how they
      shape the organisation and presentation of the database.

PMID- 15153303
TI  - The Protein Data Bank and lessons in data management.
AB  - The Protein Data Bank (PDB) is a widely used biological database of
      macromolecular structures with a long history. This history is treated as lessons
      learned and is used to highlight what are believed to be the best practices
      important to developers of biological databases today. While the focus is on data
      quality, data representation and the information technology to support these
      data, the non-data and technology issues cannot be ignored. The role of the human
      factor in the form of users, collaborators, scientific society and ad hoc
      committees is also included.

PMID- 15153304
TI  - Biological database design and implementation.
AB  - We present our experience of building biological databases. Such databases have
      most aspects in common with other complex databases in other fields. We do not
      believe that biological data are that different from complex data in other
      fields. Our experience has led us to emphasise simplicity and conservative
      technology choices when building these databases. This is a short paper of advice
      that we hope is useful to people designing their own biological database.

PMID- 15153305
TI  - Swiss-Prot: juggling between evolution and stability.
AB  - We describe some of the aspects of Swiss-Prot that make it unique, explain what
      are the developments we believe to be necessary for the database to continue to
      play its role as a focal point of protein knowledge, and provide advice pertinent
      to the development of high-quality knowledge resources on one aspect or the other
      of the life sciences.

PMID- 15153306
TI  - Globally distributed object identification for biological knowledgebases.
AB  - The World-Wide Web provides a globally distributed communication framework that
      is essential for almost all scientific collaboration, including bioinformatics.
      However, several limits and inadequacies have become apparent, one of which is
      the inability to programmatically identify locally named objects that may be
      widely distributed over the network. This shortcoming limits our ability to
      integrate multiple knowledgebases, each of which gives partial information of a
      shared domain, as is commonly seen in bioinformatics. The Life Science Identifier
      (LSID) and LSID Resolution System (LSRS) provide simple and elegant solutions to
      this problem, based on the extension of existing internet technologies. LSID and
      LSRS are consistent with next-generation semantic web and semantic grid
      approaches. This article describes the syntax, operations, infrastructure
      compatibility considerations, use cases and potential future applications of LSID
      and LSRS. We see the adoption of these methods as important steps toward simpler,
      more elegant and more reliable integration of the world's biological
      knowledgebases, and as facilitating stronger global collaboration in biology.

PMID- 15153307
TI  - Tutorial section: domains and motifs - proteins in bite-sized chunks.
AB  - Possibly the ultimate goal of bioinformatics is to be able to predict protein
      tertiary structure and chemical functionality from the initial amino acid
      sequence. Despite the best efforts of many researchers over the past two decades,
      a reliable modelling method has yet to be found and the folding problem continues
      to be a hurdle for scientists.

PMID- 15153308
TI  - Analysis for free: comparing programs for sequence analysis.
AB  - Programs to import, manage and align sequences and to analyse the properties of
      DNA, RNA and proteins are essential for every biological laboratory. This review
      describes two different freeware (BioEdit and pDRAW for MS Windows) and a
      commercial program (Sequencher for MS Windows and Apple MacOS). Bioedit and
      Sequencher offer functions such as sequence alignment and editing plus reading of
      sequence trace files. pDRAW is a very comfortable visualisation tool with a
      variety of analysis functions. While Sequencher impresses with a very user
      friendly interface and easy-to-use tools, BioEdit offers the largest and most
      customisable variety of tools. The strength of pDRAW is drawing and analysis of
      single sequences for priming and restriction sites and virtual cloning. It has a
      database function for user-specific oligonucleotides and restriction enzymes.

PMID- 15153310
TI  - The role of human mast cell-derived cytokines in eosinophil biology.
AB  - Eosinophil-mediated diseases, such as allergic asthma, eosinophilic fasciitis,
      and certain hypersensitivity pulmonary disorders, are characterized by eosinophil
      infiltration and tissue injury. Mast cells and T cells often colocalize to these
      areas. Recent data suggest that mast cells can contribute to eosinophil-mediated
      inflammatory responses. Activation of mast cells can occur by antigen and
      immunoglobulin E (IgE) via the high-affinity receptor (FcepsilonRI) for IgE. The
      liberation of proteases, leukotrienes, lipid mediators, and histamine can
      contribute to tissue inflammation and allow recruitment of eosinophils to tissue.
      In addition, the synthesis and expression of a plethora of cytokines and
      chemokines (such as granulocyte-macrophage colony-stimulating factor [GM-CSF],
      interleukin-1 [IL-1], IL-3, IL-5, tumor necrosis factor-alpha [TNF-alpha], and
      the chemokines IL-8, regulated upon activation normal T cell expressed and
      secreted [RANTES], monocyte chemotactic protein-1 [MCP-1], and eotaxin) by mast
      cells can influence eosinophil biology. Stem cell factor (SCF)-c-kit, cytokine
      cytokine receptor, and chemokine-chemokine receptor (CCR3) interactions leading
      to nuclear factor kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK)
      expression, and other signaling pathways can modulate eosinophil function.
      Eosinophil hematopoiesis, activation, survival, and elaboration of mediators can
      all be regulated thus by mast cells in tissue. Moreover, because eosinophils can
      secrete SCF, eosinophils can regulate mast cell function in a paracrine manner.
      This two-way interaction between eosinophils and mast cells can pave the way for
      chronic inflammatory responses in a variety of human diseases. This review
      summarizes this pivotal interaction between human mast cells and eosinophils.

PMID- 15153311
TI  - Epitope specificity of neutralizing antibodies against IFN-beta.
AB  - Neutralizing antibodies (NAb), a subset of antibodies against interferon-beta
      (IFN-beta) that inhibit activation of the IFN-beta receptor, are presumed to bind
      to the receptor-binding site of IFN-beta. The aim of this study was to identify
      specific epitopes for human NAb and nonneutralizing antibodies (NNAb) on the IFN
      beta molecule. Thirty-one 12-mer peptides and one 11-mer peptide representing the
      amino acid sequence of the human IFN-beta molecule were used as antigens in an
      ELISA antibody assay. Significant antibody binding was observed at residues 1-12,
      121-132, and 151-162. NNAb and NAb recognized residues 121-132 with equal
      frequency, but NAb had higher titers. NAb bound significantly more frequently to
      residues 1-12 and 151-162. There was a significant positive correlation between
      NAb titers and titers against residues 1-12. Binding to residues 1-12 was more
      pronounced in patients treated with IFN-beta1a than in patients treated with IFN
      beta1b. Our results indicate a qualitative and quantitative difference between
      NAb and NNAb, with special emphasis on the recognition of different epitopes.

PMID- 15153312
TI  - Differential upregulation of interleukin-18 receptor alpha chain between CD4+ and
      CD8+ T cells during acute graft-versus-host disease in mice.
AB  - Interleukin-18 (IL-18), a unique cytokine that stimulates both T helper 1 (Th1)
      and Th2 responses, is associated with acute graft-versus-host disease (aGVHD),
      the major limiting toxicity following allogeneic stem cell transplantation. Here,
      we investigated the mechanism underlying the upregulation of IL-18 receptor (IL
      18R) expression on T cells in murine aGVHD models. The induction of aGVHD
      elevated host serum IL-12 levels and increased expression of IL-18Ralpha chain
      (IL-18Ralpha) on engrafted T cells, in particular on CD8+ T cells. However, IL
      18Ralpha expression did not increase on the CD4+ T cells of an IL-12-deficient
      host, indicating the IL-12-dependent upregulation of IL-18Ralpha expression on
      CD4+ T cells during aGVHD. Purified donor CD8+ T cells transferred in the host
      increased IL-18Ralpha expression. In vitro experiments showed that IL-18Ralpha
      expression upregulated on CD8+ T cells but not on CD4+ T cells on stimulation
      through the T cell receptor (TCR). These results suggest that IL-18Ralpha
      expression is differentially upregulated between CD4+ and CD8+ T cells during
      aGVHD, depending on endogenous IL-12 and TCR engagement, respectively.

PMID- 15153313
TI  - Improved hepatic perfusion after iloprost infusion in patients with HCV chronic
      infection: a pilot study with possible therapeutic implications.
AB  - We performed a pilot study to evaluate whether portal flow volume (PFV) changed
      in subjects with chronic hepatitis C virus (HCV) infection with respect to
      control patients after infusion of iloprost, a prostacyclin analog. Six subjects
      with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4
      control patients affected only by HCV infection (CHCV) were studied with color
      Doppler sonography. CHCVIA patients were examined before and after 3 days of
      iloprost infusion, and CHCV patients were examined before and after 3 days with
      no treatment. In each patient, PFV was obtained after calculating portal flow
      velocity (PV), portal diameter, and portal vein cross-sectional area. The mean
      difference between basal and final values of the PFV of CHCVIA patients was
      significant (p = 0.03), as was the difference in the PFV (final values expressed
      as percent of basal values) in CHCVIA patients compared with those obtained in
      the CHCV patients (p = 0.01). We have observed significant improvement in hepatic
      perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion.
      In light of these results, we suggest some possible therapeutic implications in
      patients with HCV infection. Further studies are necessary to confirm this
      hypothesis.

PMID- 15153314
TI  - The regulation and activation of CD44 by natural killer (NK) cells and its role
      in the production of IFN-gamma.
AB  - Natural killer (NK) cells can express high levels of CD44, and signaling through
      CD44 has been shown to enhance NK cell cytotoxic activity. However, little is
      known about the factors that regulate CD44-mediated activation of NK cells. The
      studies reported here reveal that resting NK cells constitutively express CD44
      that is in an inactive form that does not bind to hyaluronan (HA), the principal
      known ligand for CD44. After infection of mice with the intracellular parasite
      Toxoplasma gondii, however, a population of NK cells that expressed activated
      CD44 emerged. To determine how expression and activation of CD44 by resting NK
      cells were regulated, the role of cytokines in these events was assessed. These
      studies revealed that whereas stimulation of resting NK cells with interleukin-12
      (IL-12) or IL-18 caused increased expression of CD44, only IL-2 or IL-15 led to
      the upregulation and activation of CD44. The cytokine-induced upregulation and
      activation of CD44 was independent of NK cell proliferation. To determine the
      functional consequences of CD44 activation, the effects of low molecular weight
      HA (LMWHA) on the production of interferon-gamma (IFN-gamma) by IL-2-activated NK
      cells were assessed. These studies showed that HA alone had little effect on the
      production of IFN-gamma, but when used in combination with IL-2, IL-12, or IL-18,
      LMWHA was a potent enhancer of IFN-gamma production. Together, these studies
      indicate an important role for proinflammatory cytokines in the activation of
      CD44 on NK cells and identify a novel pathway to enhance the ability of activated
      NK cells to produce IFN-gamma.

PMID- 15153317
TI  - NHS breast screening: the progression from one to two views.

PMID- 15153315
TI  - Plasma homocysteine and immune activation in patients with malignant melanoma
      undergoing treatment with IFN-alpha.
AB  - Immune activation and cell proliferation may contribute to the development of
      increased homocysteine concentrations in patients with malignant diseases. In
      this study, we investigated the effect of interferon-alpha (IFN-alpha) on plasma
      homocysteine concentrations in patients being treated for malignant melanoma. In
      parallel, neopterin formation and tryptophan degradation were monitored to assess
      the capacity of IFN-alpha to activate macrophages. Plasma concentrations of
      homocysteine, folate, and vitamin B(12) were determined in 15 patients with
      malignant melanoma during 12 weeks of high-dose IFN-alpha therapy. Concurrently,
      concentrations of neopterin, tryptophan, and kynurenine were measured, and the
      kynurenine/tryptophan ratio (kyn/trp) was calculated. Homocysteine and folate
      concentrations during treatment with IFN-alpha did not differ from baseline. In
      contrast, significant increases in neopterin formation and tryptophan degradation
      were apparent during IFN-alpha therapy. Plasma concentrations of vitamin B(12)
      and cysteine also increased. These results indicate that IFN-alpha directly
      activates macrophages to release neopterin and to degrade tryptophan, but
      obviously treatment with INF-alpha did not affect homocysteine metabolism.

PMID- 15153318
TI  - Is cascade testing a sensible method of population screening?

PMID- 15153319
TI  - Reattendance in the Swiss mammography screening pilot programme.
AB  - OBJECTIVES: To explore the patterns and determinants of reattendance among
      initial attendees at an organised breast cancer screening programme. SETTING:
      Swiss mammography screening pilot programme, based on first-round enrollment in
      1993-1995. METHODS: Data on socio-demographic features, health preventive
      behaviour and history, prior screening round and referring physicians' attributes
      were collected at initial attendance. First-round attendees (n=4162) were
      followed prospectively through next screening round. Determinants of reattendance
      were identified by multivariate logistic regression. RESULTS: Reattendance rate
      was high (80%). Women most likely to reattend were urban, Swiss residents with a
      true-negative first-round screening result. The more intensive the initial
      recruitment efforts, the lesser were the odds of reattendance. Mammography
      screening prior to screening enrolment increased reattendance. Having a
      gynaecologist, a female and a younger doctor as a referring physician was
      positively associated with reattendance. CONCLUSION: Mammography screening
      attendance is not only influenced by women-related factors but also by structural
      factors, and thus requires a global approach. For strategies aimed at improving
      performances of organised cancer screening programmes, understanding and
      quantification of determinants of (re)attendance are key elements to consider.

PMID- 15153320
TI  - Breast cancer detection rates, and standardised detection ratios for prevalence
      screening in the New Zealand breast cancer screening programme.
AB  - OBJECTIVES: To calculate breast cancer detection to expected incidence ratios and
      standardised detection ratios (SDRs) for the New Zealand breast cancer screening
      programme. METHOD: Breast cancer registrations for 1976-1999 were obtained from
      the New Zealand Cancer Registry. Using these registrations, the incidence in the
      absence of screening was projected for 1999 and 2000. These projections, and the
      invasive breast cancers detected in the New Zealand programme during 1999 and
      2000, were used to calculate the detection to expected incidence ratios and SDRs.
      RESULTS: In 1999, the breast cancer detection rate was 5.6 per 1000 women
      screened. The expected incidence among these women in the absence of screening
      was 2.3 per 1000, a detection to expected incidence ratio of 2.4. The SDR was
      0.84 (0.76-0.94). In 2000, the breast cancer detection rate was 6.0 per 1000
      women screened. The expected incidence among these women in the absence of
      screening was 2.4 per 1000, a detection to expected incidence ratio of 2.5. The
      SDR was 0.90 (0.81 - 0.99). CONCLUSIONS: In the first two years of the national
      programme, detection to expected incidence ratios were less than 3.0, and the SDR
      results were below 1.0. It may be unrealistic to expect new screening programmes
      to achieve SDRs of 1.0 immediately. At a similar stage, the UK National Health
      Service Breast Cancer Screening Programme (NHSBSP) also reported SDRs of less
      than 1.0 and therefore lower than expected cancer detection rates compared with
      the Swedish Two-County trial. An encouraging finding was that SDRs in five of the
      six screening regions improved in the second year of the New Zealand screening
      programme.

PMID- 15153321
TI  - CIN 2/3 and cervical cancer in an organised screening programme after an
      unsatisfactory or a normal Pap smear: a seven-year prospective study of the
      Norwegian population-based screening programme.
AB  - OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3
      and invasive cervical cancer (ICC) in an organised screening programme after an
      unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort
      study of the Norwegian population-based co-ordinated screening programme based on
      the actual diagnostic and screening procedures performed. Observations of 526,661
      women with a normal index Pap smear and 21,405 women with an unsatisfactory index
      Pap smear were made during 3.26 million women-years. METHODS: The risk of being
      diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first
      two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the
      women who were not diagnosed during the two first years was estimated by non
      parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of
      the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap
      smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of
      harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No
      increased risk of ICC was found during long-term follow-up for the 70% of the
      women with an unsatisfactory Pap smear who were returned to ordinary screening.
      Prior series of low-grade Pap smears followed by a normal Pap were associated
      with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap
      smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are
      adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated
      series of equivocal/LSIL Pap smears followed by a normal Pap should be considered
      at high risk.

PMID- 15153322
TI  - Accuracy of conventional cytology: results from a multicentre screening study in
      India.
AB  - OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate
      the accuracy of conventional cytology to detect high-grade squamous
      intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur,
      Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common
      protocol and questionnaire were used to test 22,663 women aged 25-65 years with
      conventional cytology in five cross-sectional studies. Three thresholds were used
      to define test positivity: atypical squamous cells of uncertain significance
      (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened
      women were investigated with colposcopy, and biopsies were taken when necessary.
      The reference standard for final disease status was histology or negative
      colposcopy. Data from the studies were pooled to evaluate the test
      characteristics for the detection of histologically confirmed HSIL. RESULTS: The
      test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at
      HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had
      invasive cancer. The pooled sensitivity, specificity, positive and negative
      predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4%
      respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2%
      and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%.
      The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4
      72.3% at HSIL thresholds. A significantly low sensitivity was observed in women
      aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites
      persisted even after age standardisation. CONCLUSION: The sensitivity of cytology
      varied widely between the study sites. Findings from our study and other reviews
      indicate that sustained efforts in improving sampling, preparation and reading of
      cytological specimens and improvements in clinical judgement are essential to
      achieve concurrently high sensitivity and specificity.

PMID- 15153323
TI  - Attitudes to self-sampling for HPV among Indian, Pakistani, African-Caribbean and
      white British women in Manchester, UK.
AB  - OBJECTIVE: To examine attitudes to self-sampling for human papillomavirus (HPV)
      testing among women from contrasting ethnic groups. SETTING: Manchester, UK.
      METHODS: Two hundred women of Indian, Pakistani, African-Caribbean and white
      British origin were recruited from social and community groups to participate in
      a questionnaire survey. The questionnaire included items on attitudes to self
      sampling and intention to use the test. RESULTS: Willingness to try to use the
      test was high, and women did not foresee religious or cultural barriers to self
      sampling; however, a large proportion of women were concerned about doing the
      test properly. This concern was greatest in the Indian and African-Caribbean
      groups. CONCLUSIONS: Although women's willingness to try self-sampling for HPV is
      encouraging, worries about carrying out the procedure correctly must be addressed
      if women are to feel confident about the results of self-sampling methods and
      reassured by a negative result.

PMID- 15153324
TI  - Low all-cause mortality in the volunteer-based Rotterdam section of the European
      randomised study of screening for prostate cancer: self-selection bias?
AB  - OBJECTIVES: The likelihood of self-selection bias in a cohort of men that entered
      the volunteer-based randomised prostate cancer screening trial was assessed. In
      addition, the accuracy of the randomisation was evaluated by comparison amongst
      the trial arms. SETTING: The Rotterdam section of the European Randomised Study
      of Screening for Prostate Cancer (ERSPC). Participants were recruited from
      population registries and randomised after receipt of written informed consent
      (49% participation rate). METHODS: Data from 37,614 men who entered the Rotterdam
      trial between June 1994 and July 1999 were linked to the Causes of Death Registry
      of Statistics Netherlands. For the assessment of self-selection bias, mortality
      in the trial cohort and the area of Rotterdam was compared by calculating
      standardised mortality ratios (SMRs, 95% confidence interval [CI]). Comparisons
      between the screening and the control arm were made by means of relative risk
      (RR). RESULTS: There were a total of 1661 deaths (4.4%) in the trial cohort,
      during an average follow-up time of 2.8 years. The observed number of deaths in
      the two arms combined was lower than expected (SMR 86.7%, 95% CI 81.6-92.1),
      which was reflected in the major cause of death categories, especially in all
      malignant neoplasms. No difference was observed in the all-cause mortality rate
      among the screening and control arm, aged 55-69 years at entry (RR 1.00, 95% CI
      0.89-1.12), nor when all causes, excluding prostate cancer mortality, were
      considered. CONCLUSIONS: The preliminary results show that the screening and the
      control arm were comparable, but men recruited for the trial seemed healthier
      than men in the target population.

PMID- 15153325
TI  - Strategies to improve the effectiveness of abdominal aortic aneurysm screening
      programmes.
AB  - OBJECTIVE: Ruptured abdominal aortic aneurysms (rAAAs) occurring in patients with
      screen-detected aneurysms could be regarded as a failure of screening and reduce
      effectiveness of screening. To understand this issue, we studied the reasons why
      rAAAs occur in screened patients and estimated the cost-benefit ratio if these
      ruptures could be prevented. METHODS: All rAAAs occurring in the Huntingdon
      district in the UK during the study period (1991-2000) were traced via a
      combination of hospital admission, accident and emergency attendance, and
      intensive therapy unit admission records, operating theatre registers and post
      mortem reports. Cross-referencing with the aneurysm-screening database identified
      those patients who had attended screening. Previously used cost-effectiveness
      models were used to estimate the cost benefits to screening. RESULTS: Ninety
      three rAAAs occurred in men over the study period, of whom 23 (25%) had been
      invited for screening and 13 (14%) had accepted the invitation. All who had been
      screened (mean age 75 [65-82]) had abnormal aortic diameters (>30 mm) on their
      first scan. Of those invited, 10/23 (43%) did not attend their screening
      appointment, 4/23 (17%) were deemed not fit for open surgery, 4/23 (17%) ruptured
      whilst being assessed for aneurysm repair, 2/23 (9%) ruptured whilst under six
      monthly surveillance, and 3/23 (13%) failed to attend scheduled six-monthly
      surveillance appointments. Reducing screened ruptures by one half could increase
      the cost-effectiveness of screening by 27%. CONCLUSION: There were no failures of
      the screening test. The benefits of aneurysm screening can be improved by
      increasing the uptake of screening, the compliance with surveillance, and by
      streamlining the work-up process before surgery.

PMID- 15153326
TI  - Cost-effectiveness of a community-based screening programme for chronic atrial
      fibrillation in Japan.
AB  - OBJECTIVES: To examine the cost-effectiveness of a community-based screening
      programme for chronic atrial fibrillation (AF) in Japan. METHODS: Using a
      computer model of a Markov process, the cost-effectiveness of an annual ECG
      screening programme and an annual pulse palpation screening programme for
      arrhythmia were compared with no screening. A hypothetical Japanese population of
      65 year old individuals was followed until 85 years of age. We assumed that
      individuals with irregular beats on palpation were worked up by ECG and that ECG
      was perfect in detecting AF, whereas palpation was not. It was also assumed that
      patients diagnosed with AF received anticoagulant therapy, that some AF patients
      developed ischaemic stroke, and that some on anticoagulant therapy developed
      intracranial or gastrointestinal haemorrhage. Costs, efficacy of anticoagulation,
      utility of health status, and clinical variables were estimated from the
      literature. Outcomes were expressed as US dollars per quality-adjusted life-year
      (QALY). RESULTS: Both annual ECG screening programme and annual palpation
      screening programme were more costly and at the same time more effective compared
      with no screening, with their incremental cost-effectiveness ratios approximately
      US$8000 per QALY in males and US$10,000 per QALY in females. Sensitivity analyses
      showed high sensitivity of cost-effectiveness ratios to the incidence of
      ischaemic stroke and anticoagulants prescription rate. Two annual screening
      programmes were similar in effectiveness and costs. CONCLUSION: To prevent
      ischaemic stroke associated with AF, both annual ECG screening and annual
      palpation screening were favourable in the context of conventional criteria for
      cost-effectiveness.

PMID- 15153327
TI  - Measurement of haemoglobin as a screening test in general practice.
AB  - OBJECTIVE: To assess the validity of using the measurement of haemoglobin as a
      primary screen test at point-of-care in general practice. METHODS: 1100
      consecutive full blood counts carried out at Hammersmith Hospital haematology
      laboratory on blood samples sent by the general practitioners in the area were
      reviewed. Where haemoglobin was in the normal range all the parameters of a full
      blood count were checked and a blood film was screened in order to identify any
      abnormal features occurring in the absence of anaemia. RESULTS: Haemoglobin was
      normal in 81% of the samples, and in 81% of this set none of the blood count
      components showed any abnormal features (i.e. outside two standard deviations of
      normal reference range). The remaining 19% of cases included 32 with iron
      deficiency, 26 with high MCV, 84 with leucocyte abnormalities (neutrophilia,
      neutropenia, lymphocytosis, eosinophilia, monocytosis) and 19 with platelet
      counts either too high or too low. The predictive value of a normal full blood
      count from a normal haemoglobin was 0.81. However, when the limits of normal
      reference values were set at three standard deviations only 7% of the cases
      showed abnormal features and the predictive value of normality from a normal
      haemoglobin increased to 0.92. CONCLUSION: There are now simple and suitable
      devices available for measuring haemoglobin at point-of-care, away from a
      laboratory. This provides a useful screening test in general practice as a full
      blood count would, as a rule, be required only in the small proportion of cases
      where anaemia is detected or the patient's history and/or clinical signs
      specifically indicate the need for this further investigation. This approach
      should contribute to more efficient, convenient and economical practice without
      compromising clinical management.

PMID- 15153328
TI  - Effect of folic acid fortification on prevalence of neural tube defects in Rhode
      Island.

PMID- 15153330
TI  - The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast
      tumor cells.
AB  - p300/CBP-associated factor (PCAF) is a coactivator of the tumor suppressor, p53.
      PCAF participates in p53's transactivation of target genes through acetylation of
      both bound p53 and histones within p53 target promoters. Using microarrays, we
      discovered that PCAF itself is induced by p53 in a panel of breast tumor cell
      lines. Two p53 mutant breast tumor cell lines, BT-549 and UACC-1179, were chosen
      for further study of PCAF induction by wild-type p53. PCAF induction following
      adenoviral transduction of p53 expression was confirmed with real-time polymerase
      chain reaction in a time course experiment. Chromatin immunoprecipitation
      experiments then showed that PCAF induction was associated with increased p53
      binding to the PCAF promoter, which contains p53 consensus-binding sites. PCAF
      induction by p53 activity was further demonstrated in wild-type p53 MCF10A cells
      when PCAF expression was induced following activation of endogenous wild-type p53
      with doxorubicin in a dose- and time-dependent manner. Furthermore, the
      doxorubicin-induced increase in PCAF expression was blocked by pretreatment of
      the MCF10A cells with siRNA (small interfering RNA) targeted against p53 mRNA.
      Taken together, the results show that PCAF expression can be induced by wild-type
      p53.

PMID- 15153331
TI  - Glutathione depletion induced by c-Myc downregulation triggers apoptosis on
      treatment with alkylating agents.
AB  - Here we investigate the mechanism(s) involved in the c-Myc-dependent drug
      response of melanoma cells. By using three M14-derived c-Myc low-expressing
      clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger
      apoptosis in the c-Myc antisense transfectants, but not in the parental line. On
      the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce
      apoptosis to the same extent regardless of c-Myc expression. Because we
      previously demonstrated that c-Myc downregulation decreases glutathione (GSH)
      content, we evaluated the role of GSH in the apoptosis induced by the different
      drugs. In control cells treated with one of the alkylating agents or the others,
      GSH depletion achieved by L-buthionine-sulfoximine preincubation opens the
      apoptotic pathway. The apoptosis proceeded through early Bax relocalization,
      cytochrome c release, and concomitant caspase-9 activation, whereas reactive
      oxygen species production and alteration of mitochondria membrane potential were
      late events. That GSH was determining in the c-Myc-dependent drug-induced
      apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc
      low-expressing cells up to the level of controls. Indeed, GSH ethyl ester
      mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan
      by inhibition of Bax/cytochrome c redistribution. The relationship among c-Myc,
      GSH content, and the response to alkylating agent has been also evaluated in the
      M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense
      transfectants. All together, these results demonstrate that GSH plays a key role
      in governing c-Myc-dependent drug-induced apoptosis.

PMID- 15153332
TI  - Amplification of SKI is a prognostic marker in early colorectal cancer.
AB  - BACKGROUND: Improved risk stratification of early colorectal cancer might help to
      better select patients for adjuvant treatment. Alterations in the transforming
      growth factor-beta (TGF-beta) pathway have frequently been found in colorectal
      cancer, but their impact on prognosis remains controversial. We therefore
      analyzed two transcriptional corepressors of the TGF-beta signaling pathway with
      respect to prognosis and prediction of chemotherapy benefit in early colorectal
      cancer. METHODS: The gene copy status of SKI and SNON was analyzed by use of
      quantitative real-time polymerase chain reaction in 179 colorectal tumor
      biopsies, which had been collected from a randomized multicenter trial of the
      Swiss Group for Clinical Cancer Research (SAKK). RESULTS: Partial or complete
      allelic loss was found in 41.5% and 55.2% for SKI and SNON, whereas amplification
      was found in 10.1% and 15.1%, respectively. Multivariate Cox analysis showed that
      gene amplification of SKI independently predicted reduced relapse-free [hazard
      ratio (HR) for relapse 2.08, P =.049] and overall survival (HR for death 2.62, P
      =.012). In contrast, deletion of SKI and the gene copy status of SNON were not
      significantly correlated with prognosis. CONCLUSION: Amplification of SKI is a
      negative prognostic marker in early-stage colorectal cancer. This marker should
      help to improve risk stratification to better select patients for adjuvant
      therapy. Confirmatory investigations are warranted.

PMID- 15153333
TI  - Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel
      regression in human squamous cell carcinomas grown in nude mice caused by VEGF
      receptor 2 blockade with DC101.
AB  - The purpose of our study was the investigation of early changes in tumor
      vascularization during antiangiogenic therapy with the vascular endothelial
      growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced
      magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human
      skin squamous cell carcinomas in nude mice were treated with DC101. Animals were
      examined before and repeatedly during 2 weeks of antiangiogenic treatment using
      Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic
      data were parameterized in "amplitude" (increase of signal intensity relative to
      precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were
      validated by parallel examinations of histological sections immunostained for
      blood vessels (CD31). Already 2 days after the first DC101 application, a
      decrease of tumor vascularization was observed, which preceded a reduction of
      tumor volume. The difference between treated tumors and controls became prominent
      after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02).
      In line with change of microvessel density, the decrease in amplitudes was most
      pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/-
      843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different
      (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/-
      93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P
      =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in
      human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a
      valuable tool for early detection of treatment effects before changes in tumor
      volume become apparent.

PMID- 15153334
TI  - Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a
      biphasic apparent diffusion coefficient change as potential early MRI response
      marker.
AB  - The goal of this study was to examine the use of diffusion-weighted magnetic
      resonance imaging (DW-MRI) for the assessment of early progression of photodamage
      induced by Pd-bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT).
      TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors
      developed in our laboratory and presently under clinical trials for prostate
      cancer (PC) therapy. Using the subcutaneous human prostate adenocarcinoma WISH
      PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent
      diffusion coefficient (ADC) was observed within the first 24 hours post-PDT, with
      initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon
      enables the detection of successful tumor response to PDT within 7 hours
      posttreatment. This process was validated by direct, histological, and
      immunohistochemical examinations and also by evaluation of serum prostate
      specific antigen (PSA) levels that decreased significantly already 7 hours
      posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT
      induced decrease in ADC, suggesting that lipid peroxidation (LPO) significantly
      contributes to ADC decline observed after PDT. These results demonstrate that
      TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and
      suggests DW-MRI to be useful for the detection of early tumor response and
      treatment outcome in the clinical setting.

PMID- 15153335
TI  - Urine telomerase: an important marker in the diagnosis of bladder cancer.
AB  - Telomerase activity is present in most human malignant tumors, whereas it is
      generally not detectable, with some exceptions, in normal cells. Therefore, it
      represents a potential tool for tumor detection. In the present study, telomerase
      activity was determined in urine from 79 healthy individuals and 121 previously
      untreated bladder cancer patients using a highly sensitive telomeric repeat
      amplification protocol (TRAP) assay and the results were expressed as arbitrary
      enzymatic units (AEU). This approach enabled us to identify cutoff values
      characterized by high sensitivity (from 75% to 93%) and specificity (from 72% to
      92%). Moreover, analysis as a function of gender showed a higher accuracy of TRAP
      assay in males (93% sensitivity and 90% specificity at the cutoff of 50 AEU) than
      in females. This sensitivity was confirmed in patients with nonassessable or
      negative cytology. In women, morphological and immunocytochemical determinations
      using a monoclonal antibody (anti-hTERT) recently developed in our laboratory
      showed a large fraction of immunoreactive inflammatory or nonbladder cells, which
      may justify the false-positive TRAP results. In conclusion, this assay represents
      an important noninvasive diagnostic tool to detect bladder cancer also in
      patients with negative or nonassessable urine cytology and with low-grade and
      early-stage lesions.

PMID- 15153336
TI  - High-resolution analysis of gene copy number alterations in human prostate cancer
      using CGH on cDNA microarrays: impact of copy number on gene expression.
AB  - Identification of target genes for genetic rearrangements in prostate cancer and
      the impact of copy number changes on gene expression are currently not well
      understood. Here, we applied high-resolution comparative genomic hybridization
      (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH
      microarrays identified most of the alterations detected by classic chromosomal
      CGH, as well as a number of previously unreported alterations. Specific recurrent
      regions of gain (28) and loss (18) were found, and their boundaries defined with
      sub-megabasepair accuracy. The most common changes included copy number decreases
      at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as
      at 13q (33-44, 49-51, and 74-76 Mbp from the p-telomere), which matched with
      minimal regions of loss seen in extensive loss of heterozygosity mapping studies
      of large numbers of tumors. Previously unreported recurrent changes were found at
      2p, 2q, 3p, and 17q (losses), and at 3q, 5p, and 6p (gains). Integration of
      genomic and transcriptomic data revealed the role of individual candidate target
      genes for genomic alterations as well as a highly significant (P <.0001) overall
      association between copy number levels and the percentage of differentially
      expressed genes. Across the genome, the overall impact of copy number on gene
      expression levels was, to a large extent, attributable to low-level gains and
      losses of copy number, corresponding to common deletions and gains of often large
      chromosomal regions.

PMID- 15153337
TI  - Inhibition of tumor growth and angiogenesis by soluble EphB4.
AB  - EphB receptors and their ephrinB ligands play a key role in the formation of a
      regular vascular system. Recent studies have also shown the involvement of
      Eph/ephrin interactions in malignant tumor progression and angiogenesis. We have
      generated soluble monomeric EphB4 (sEphB4)-expressing A375 melanoma cells to
      study the effect of dominant negatively acting sEphB4 on tumor growth and
      angiogenesis. Soluble EphB4-expressing A375 tumors grown subcutaneously in nude
      mice show dramatically reduced tumor growth compared to control tumors. The
      proliferative capacity of sEphB4-expressing cells in monolayer culture is not
      altered. Yet, sEphB4-expressing A375 cells cannot establish proper cell-cell
      contacts in three-dimensional spheroids. However, sEphB4 transfectants have
      reduced proliferation and apoptosis rates when grown in three-dimensional culture
      in vitro or in subcutaneous tumors in vivo. Analysis of the vascular phenotype of
      the tumors revealed a reduction of intratumoral microvessel density in sEphB4
      expressing tumors. Corresponding to these mouse experiments, a matched pair
      analysis of EphB4 and ephrinB2 expression in human colon carcinomas revealed
      significantly upregulated levels of EphB4 expression compared to adjacent normal
      tissue. Taken together, the data identify dual effects of sEphB4 on the tumor and
      the vascular compartment that collectively inhibit tumor growth.

PMID- 15153338
TI  - Spontaneous immortalization of clinically normal colon-derived fibroblasts from a
      familial adenomatous polyposis patient.
AB  - Normal human diploid cells do not spontaneously immortalize in culture, but
      instead enter replicative senescence after a finite number of population
      doublings. Ablation of key checkpoint arrest or cancer-suppressor genes, through
      dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene
      expression (SV40 large T, HPV16/18, and E6/E7) can lead to escape from
      senescence, additional doublings, and entrance into crisis phase, where immortal
      clones emerge at low frequency. In the vast majority of cases, telomerase is
      reactivated and telomeres are stabilized. Here we describe the spontaneous
      immortalization of clinically normal fibroblasts derived from colonic stroma of a
      familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the
      spontaneously immortalized derivative (C26Ci) cells are heterozygous for a
      characterized germline mutation in exon 15 of the adenomatous polyposis coli
      gene. Immortalization was accompanied by spontaneous reactivation of endogenous
      telomerase and establishment of telomeres at presenescent lengths. Normal
      checkpoint behavior is retained and a diploid karyotype is maintained. These
      cells provide a valuable new addition to the limited number of spontaneously
      immortalized human cell types, particularly fibroblast cells, and will be useful
      in experimentally determining the functional pathways in neoplastic development
      and in the identification of potential molecular targets for cancer
      chemoprevention.

PMID- 15153340
TI  - CREB regulates AChE-R-induced proliferation of human glioblastoma cells.
AB  - The cyclic adenosine monophosphate (AMP) response element-binding protein, CREB,
      often modulates stress responses. Here, we report that CREB suppresses the
      glioblastoma proliferative effect of the stress-induced acetylcholinesterase
      variant, AChE-R. In human U87MG glioblastoma cells, AChE-R formed a triple
      complex with protein kinase C (PKC) epsilon and the scaffold protein RACK1,
      enhanced PKCepsilon phosphorylation, and facilitated BrdU incorporation. Either
      overexpressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein
      kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressed
      this proliferation, suggesting that CREB's repression of this process involves a
      PKC-mediated pathway, whereas impaired CREB regulation allows AChE-R-induced, PKA
      mediated proliferation of glioblastoma tumors.

PMID- 15153341
TI  - Glioma tropic neural stem cells consist of astrocytic precursors and their
      migratory capacity is mediated by CXCR4.
AB  - Malignant gliomas spawn disseminated microsatellites, which are largely
      refractory to currently employed therapies, resulting in eventual tumor
      recurrence and death. The use of tumor-tropic neural stem cells (NSCs) as
      delivery vehicles for therapeutic gene products represents an attractive strategy
      specifically focused at treating these residual neoplastic foci. We wished to
      elucidate the biological cues governing NSC tropism for glioma. In this context,
      we describe that tumor-tropic NSCs comprise largely of astrocytic progenitors
      expressing chemokine receptor 4 (CXCR4). Blocking of CXCR4 significantly inhibits
      NSC migration toward the tumor. These findings define specific characteristics
      associated with the cell populations within transplanted NSCs that demonstrate
      glioma-tracking behavior.

PMID- 15153339
TI  - Tax-independent constitutive IkappaB kinase activation in adult T-cell leukemia
      cells.
AB  - Adult T-cell leukemia (ATL) is a fatal T-cell malignancy that arises long after
      infection with human T-cell leukemia virus type I (HTLV-I). We reported
      previously that nuclear factor-kappaB (NF-kappaB) was constitutively activated in
      ATL cells, although expression of the viral proteins was barely detectable,
      including Tax, which was known to persistently activate NF-kappaB. Here we
      demonstrate that ATL cells that do not express detectable Tax protein exhibit
      constitutive IkappaB kinase (IKK) activity. Transfection studies revealed that a
      dominant-negative form of IKK1, and not of IKK2 or NF-kappaB essential modulator
      (NEMO), suppressed constitutive NF-kappaB activity in ATL cells. This IKK
      activity was accompanied by elevated expression of p52, suggesting that the
      recently described noncanonical pathway of NF-kappaB activation operates in ATL
      cells. We finally show that specific inhibition of NF-kappaB by a super-repressor
      form of IkappaBalpha (SR-IkappaBalpha) in HTLV-I-infected T cells results in cell
      death regardless of Tax expression, providing definitive evidence of an essential
      role for NF-kappaB in the survival of ATL cells. In conclusion, the IKK complex
      is constitutively activated in ATL cells through a cellular mechanism distinct
      from that of Tax-mediated IKK activation. Further elucidation of this cellular
      mechanism should contribute to establishing a rationale for treatment of ATL.

PMID- 15153342
TI  - [Bed rest or early mobilization as treatment of deep vein thrombosis: a
      systematic review and meta-analysis].
AB  - BACKGROUND AND OBJECTIVE: We aimed to know if treatment of deep vein thrombosis
      (DVT) with early mobilisation is as safe and effective as bed rest. MATERIAL AND
      METHOD: MEDLINE, EMBASE, Cochrane library (CCTR), Spanish Medical Index, and MD
      Consult Virtual Library databases were searched. We also cross-checked
      bibliographies of the retrieved articles. The TESEO database of doctoral theses
      in Spain was also revised. We only searched for clinical trial articles comparing
      bed rest with early mobilization with respect to the incidence of objectively
      diagnosed pulmonary embolism (PE) in patients treated for DVT of lower limbs. The
      concordance coefficient was evaluated by statistical methods. We used relative
      risk and 95% confidence intervals. Selection bias was evaluated using funnel
      plot. RESULTS: Only three articles were included in the metaanalysis, with 296
      patients randomized from 773 patients initially evaluated, with a follow-up of 9
      days to 3 months. Quality rating ranged from 61.4 to 90% and the kappa index of
      concordance ranged from 0.78 to 0.93. The relative risks of PE between the two
      groups of treatment (early mobilization versus bed rest) were 1.31 (0.63-2.72),
      1.50 (0.17-13.23), and 1.45 (0.56-3.75), respectively, and the global RR was 1.37
      (0.78-2.40). CONCLUSIONS: The analyzed studies reveal that the treatment of DVT
      with early mobilization rather than bed rest neither increases the rate of PE nor
      increases the complication rate. New well designed, controlled clinical trials
      are needed to confirm the conclusions of this review.

PMID- 15153343
TI  - [Home intravenous antibiotic treatments in cystic fibrosis units of Madrid].
AB  - BACKGROUND AND OBJECTIVE: A descriptive study of the home intravenous antibiotic
      treatment (HIVAT) course in cystic fibrosis (CF) units of Madrid in an 18 month
      period. Different patient features were recorded, antibiotherapy, intravenous
      access, complications and their resolutions. We accessed the improvement of the
      pulmonary function, forced vital capacity (FVC) and forced expiratory volume in
      one second (FEV1) at the end of the treatment. PATIENTS AND METHOD: For an 18
      months period (January 2002-June 2003) the patients with CF who received HIVAT
      and fulfilled the previously fixed criteria were included. The next clinic
      variables were collected: age, sex, bacterial colonization of respiratory tree,
      pancreatic function and pulmonary function in steady phase, before and after
      HIAT. RESULTS: 56 patients, 31 male and 25 female, were given 90 courses of HIAT
      (34 patients received only one course). Mean age was 20.06 (8.07) years. 57.1% of
      the patients were colonized by Pseudomonas aeruginosa. The most frequently used
      antibiotics were ceftazidime and tobramycin. Courses of treatment lasted a mean
      of 4.08 (5.09) days inpatient and 11.89 (4.96) at home. In 87.7% of the course
      were used the intravenous cannulae, Port-a-cath in 6.7% and Venocath in 7.8%. The
      intravenous access was replaced, in the 64.4% of the cases, by the nurse of the
      CF Unit, in the 21.4% in the emergency room of the nearest hospital and in 11.9%
      in primary care center. Three occasions skin reactions were reported. The
      parameters of pulmonary function improved significatively after HIVAT.
      CONCLUSIONS: The HIVAT is a therapeutic option that, following predetermined
      inclusion criteria, has a low complication rate and improves pulmonary function.

PMID- 15153345
TI  - [Inhibitors of fusion: a new alternative in the treatment of HIV infection].

PMID- 15153344
TI  - [Characteristics of avoidable hospitalization in Spain].
AB  - BACKGROUND AND OBJECTIVE: Hospitalizations that could have been prevented with a
      timely and effective ambulatory care are known as avoidable hospitalizations
      (AH). The measure of AH is an indicator of the quality of primary health care
      centers. The objective of this study was to determine the factors that influence
      the level of AH at the Spanish public hospitals. MATERIAL AND METHOD: We
      identified the characteristics of hospitalised patient as AH. We studied the
      total hospitalizations in public hospitals of Spain in 2000 related to AH.
      RESULTS: AH admissions were the 15.8% of total in Spanish hospitals and the 16.6%
      of hospital stays. Patients' mean age was high, 54 years, males (age-adjusted OR
      = 1.54) with a large length of stay and presurgery stay, higher comorbidity (0.63
      [0.8]), public financing, and admission was basically emergency-caused and in
      high complexity hospitals. There is a direct relationship between frequency of AH
      and hospital complexity. CONCLUSIONS: The control of AH is very important because
      its repercussion on the total hospitalary case-mix. We observe an inducing effect
      of the hospital offer because the hospital capacity increase the number of AH
      admissions.

PMID- 15153346
TI  - [New review of uniformity requirements for manuscripts submitted to biomedical
      journals: pay attention to ethics!].

PMID- 15153348
TI  - [Analysis of uncertainty in the economic assessment of health interventions].

PMID- 15153347
TI  - [Primary non-lymphoid thymic neoplasms. A study of 58 cases].
AB  - BACKGROUND AND OBJECTIVE: Primary non-lymphoid thymus tumors (PNLTT) are an
      uncommon though quite varied pathology. Our objective was to identify the
      clinical, therapeutic and histologic variables with a prognostic value in these
      neoplasms. PATIENTS AND METHOD: We studied 58 PNLTT cases, corresponding to 52
      epithelial neoplams (PTEN), 4 thymolipomas (7%) and 2 neuroendocrine tumors (3%).
      Commonest clinical manifestations were myasthenia gravis (41%) and dyspnea (21%).
      Three patients were symptom-free (24%). We used Kaplan-Meier survival curves and
      Cox regression model. RESULTS: All patients underwent surgery which consisted of
      thymectomy. Four patients underwent a biopsy procedure alone. Perioperative
      mortality was 3% (n = 2) and morbidity was 31% (n = 18), mainly because of
      respiratory and wound problems. 24 patients with PTEN, Masaoka degrees III and
      IV, and a patient with a lymphoepithelial carcinoma received adjuvant
      chemotherapy and/or radiotherapy. With a follow-up of 13 + 5 years, 12 PTEN
      patients and one patient with a neuroendrocrine tumor died as a consequence of
      the evolution of the disease. Cumulative survival was 80% at 5 years, 71% at 7
      years and 63% at 10 years. There are currently two local relapses in two PTEN
      cases after 9 and 8 years of follow-up, respectively. Main prognostic factors are
      the histologic type and subtype and the clinical stage (p < 0.001). CONCLUSIONS:
      In PNLTT early diagnosis is crucial in order to administer a correct treatment
      before the clinical stage is more advanced. Main prognostic factors are the
      histologic type and subtype and the clinical stage.

PMID- 15153349
TI  - [Safety of antiepileptic drugs during pregnancy].

PMID- 15153351
TI  - [Hepatotoxicity due to Camelia sinensis].

PMID- 15153353
TI  - [Thoughts on the clinical report of the case of suprarenal carcinoma and
      hypokalemia].

PMID- 15153350
TI  - [Sequential thrombosis and spontaneous muscular haemorrhage in the primary
      antiphospholipid syndrome].

PMID- 15153354
TI  - [Ibuprofen, aseptic meningitis, systemic lupus erythematosus].

PMID- 15153355
TI  - [Changes in empiric therapy for nosocomial pneumonia due to the emergence of
      bacterial strains with broad spectrum beta-lactamases].

PMID- 15153356
TI  - [Sentinel lymph node biopsy in breast cancer].

PMID- 15153357
TI  - [Comparative study of the different radiotracer administration route to locate
      the sentinel node in breast cancer].
AB  - AIM: To assess the results of Sentinel Lymph Node (SLN) detection in breast
      cancer patients depending on the radiotracer injection route, especially
      evaluating which route that makes it possible to identify the highest percentage
      of SLNs and its detection in the inner mammary chain. METHODS: We prospectively
      studied 120 breast cancer patients. Three groups of 40 patients each were
      established depending on the radiotracer injection route. 1) Subdermal or
      subareolar route: 18 T1 and 22 T2, mean tumor diameter size of 1.76 cm. 2)
      Peritumoral route: 16 T1 and 24 T2, mean tumor diameter size of 1.86 cm. 3)
      Intratumoral route: 20 T1 and 20 T2, mean tumor diameter size of 1.61 cm. The day
      before surgery, a lymphoscintigraphic study was performed in all cases and
      intraoperative SLN resection was carried out with the aid of a hand-held gamma
      probe. RESULTS: The SLN was identified in 38/40 cases (95%) of group 1, in 35/40
      cases (88%) of group 2 and in 38/40 cases (95%) of group 3. No SLNs in the
      mammary chain were observed in patients who underwent subdermal/subareolar
      injection of the radiotracer. On the other hand, SLNs were visualized in this
      location in 4/35 patients with peritumoral injection (11%) and in 8/38 patients
      with intratumoral injection (21%). CONCLUSION: The superficial (subdermal,
      subareolar) injection technique is more suitable when an unnecessary
      lymphadenectomy has to be prevented in cases without axillary metastases. The
      deeper injection technique (peritumoral, intratumoral) should be use when,
      moreover, we seek accurate staging or plan non-systematic mammary chain
      irradiation.

PMID- 15153358
TI  - [Extraosseous accumulation of 99mTc-HMDP in knees with synovial effusion].
AB  - In the presence of extraosseous activity seen in the late phase of the bone
      scintigraphy (BS) localized in the distal femur of patients prior to radiation
      synovectomy, we decided to review the frequency of this finding in 20 patients
      (24 joints) and its relationship with scintigraphic and clinical parameters. Mild
      soft tissue accumulation was seen in the late phase of the BS in 14 out of 24
      joints, without association between this finding and knee uptake in vascular
      blood pool and late phases of the BS. However, a significant association with
      synovial effusion was found, and patients with higher degree of effusion
      presented extraosseous activity more frequently. In conclusion, we think that
      soft tissue accumulation in the late phase of the BS is a sign of synovial
      effusion.

PMID- 15153359
TI  - [Contribution of the scintigraphy with iodocholesterol (I-COL) to the diagnosis
      and characterization of silent adrenal masses].
AB  - OBJECTIVE: To assess the role of the adrenal cortical scintigraphy with 131-I
      Norcholesterol (I-COL) in the diagnosis and characterization of silent adrenal
      masses. METHODS: We selected 57 patients who underwent an adrenal scintigraphy
      with I-COL, 36 women and 21 men (mean aged: 62.5 years), and who were classified
      into two groups: Group I or Incidentalomas, 39 patients without signs or symptoms
      of adrenal disease in whom an adrenal mass is incidentally discovered during a CT
      or ultrasound scan; and a second group or Group II, 18 patients with history of
      cancer in whom an adrenal mass is discovered. We defined the following
      Scintigraphic patterns in relationship with the CT: Normal, concordant unilateral
      (CU) or exclusive; discordant unilateral (DU); concordant asymmetrical (CA) or
      prevalent; discordant asymmetrical (DA) and nonvisualization (NV). The final
      diagnosis was obtained with clinical, analytical, and radiological evaluation and
      in some cases surgery. RESULTS: In Group I, the diagnoses were: 17 adrenal masses
      without criteria of malignancy or hormonal overproduction (the Scintigraphic
      patterns were 10 CA, 5 normal and 2 CU), 9 Subclinical Cushing's syndrome (4 CU,
      4 CA and 1 normal), 5 adenomas (all CU), 3 adrenal primary carcinomas, with no
      uptake in the scintigraphy, and 5 were other diagnoses. In group II, 14 patients
      had benign masses (all patterns were normal or concordant) and 4 patients
      metastases (3 discordant and 1 NV patterns). The follow-up time was at least one
      year. CONCLUSIONS: The adrenal cortical scintigraphy with I-COL provides us
      information on the functional status of silent adrenal masses and it is an useful
      tool to distinguish benign from malignant lesions; for this reason we considered
      that it must be integrated in the diagnostic algorithm as a complement to other
      techniques.

PMID- 15153360
TI  - [Absence of chromosomic and genotoxic damage from the radiation dose administered
      in scintigraphic examinations].
AB  - INTRODUCTION: The cytokinesis-blocked (CB) micronucleus test (MN) on irradiated
      human lymphocytes is normally used to evaluate chromosomal and genotoxic damage
      produced by various physical and chemical agents. OBJECTIVE: Determine any
      possible genotoxic effect induced by the different types of ionizing radiation
      employed in medical diagnostic radiology and nuclear medicine. MATERIAL AND
      METHODS: The frequency of the MN appearance was determined in CB lymphocyte
      cultures of a total of 4 different groups of patients: (1) in 35 supposedly
      healthy volunteers to establish the MN spontaneous frequency in the medium; (2)
      in 9 volunteers to measure the in vitro dose-response curves in order to
      calculate the MN frequency following X-ray irradiation and gamma radiation; (3)
      in 25 patients in whom a specific diagnostic and/or therapeutic procedure
      employing diagnostic radiology techniques involving X-ray exposure was applied,
      and (4) in 26 patients in whom the diagnostic procedure in question involved
      nuclear medicine techniques (scintiscan). RESULTS: A lineal relationship was
      observed between the MN frequency and the dose of ionizing radiation administered
      in vitro, both in X-rays and gamma radiation. A significant increase in the MN is
      observed after radiation is given to patients during medical diagnostic radiology
      examinations when compared with the control values obtained from the same
      patients prior to being subjected to the radiological procedure (p < 0.01). No
      significant MN increase is observed following exposure to radiation involved in
      diagnostic examinations in patients studied in Nuclear Medicine. CONCLUSION:
      Ionizing radiation employed in complex medical diagnostic radiology examinations
      produces a significant increase in the MN appearance frequency and as such
      indicates both radiation induced chromosomal and genotoxic damage. However, the
      ionizing radiation used in diagnostic nuclear medicine examinations does not
      induce any significant increase in MN appearance frequency.

PMID- 15153362
TI  - [Ochronotic arthropathy: the value of bone scintigraphy in alkaptonuria].
AB  - We report the case of a 62 year old man diagnosed of alkaptonuria who was
      referred to our department to undergo bone scintigraphy for polyarthralgia. The
      patient had a history of pain in lumbar and thoracic spine, right shoulder and
      left knee. Bone scintigraphy showed multiple joint disease with increased uptake
      in both shoulders, knees and spine. Higher uptake stood out in painful right
      shoulder and left knee joints. Ochronotic arthropathy that is developed in
      alkaptonuric patients is a degenerative joint disease. X-ray studies in this
      patient showed marked degenerative arthrosis in knees and shoulders, without more
      intense involvement in the symptomatic joints. Lumbar spine X-rays showed
      intervertebral disk calcification with disk collapse and fusion of the vertebral
      bodies with relative sparing of sacroiliac joint, which is a classic feature of
      ochronotic arthropathy. This case highlights the utility of bone scintigraphy in
      the evaluation of joint involvement as well as its correlation with clinical
      course and potential usefulness in the follow-up of this disease.

PMID- 15153361
TI  - (Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine
      therapy.
AB  - As salivary glands concentrate radioiodine the radiation injury associated with
      131I-therapy may result in sialoadenitis and xerostoma leading to a lasting
      impaired quality of life. Recently we reported about prostaglandin concentration
      changes as biochemical markers for radiation injury. Isoprostanes, a new family
      of prostaglandin-like compounds, have been demonstrated to be reliable markers
      for oxidation injury in vivo. PATIENTS AND METHODS: In this study we examined the
      levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24
      patients undergoing 1311 treatment in different doses for hyperthyroidism and
      differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were
      monitored in parallel. Saliva(iso)prostaglandins were determined before 131I
      treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after
      therapy. RESULTS: 8-epi-PGF2alpha showed a significant 1311 dose-dependent
      temporary increase. The alterations were comparable in all investigated patients
      and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose
      dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha
      lower as compared to non-smokers. CONCLUSION: These results clearly demonstrate a
      dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8
      epi-PGF2alpha) after 131I-therapy in the salivary glands.

PMID- 15153364
TI  - [Diagnosis and assessment of therapeutic response of bone metastases by bone
      scintigraphy and PET study].
AB  - Nuclear medicine plays an important role in staging and evaluation of the initial
      extension and response to treatment of bone metastases. In order to accurately
      read Bone Scintigraphy (BS) and Positron Emission Tomography scan (PET)
      procedures, it is essential to understand the different behavior of these
      studies. We present a case report of a woman treated for breast cancer, with
      suspicion of recurrent disease due to increase of tumor markers. Initial BS
      showed non-conclusive findings, whereas PET study was consistent with a spread of
      bone metastases. The patient underwent both procedures again after a course of
      chemotherapy. Post-treatment BS showed progression of bone lesions, while PET
      showed good therapeutic response. The PET demonstrates lesions earlier and more
      effectively than the bone scintigraphy in the evaluation of the therapeutic
      response of bone metastases.

PMID- 15153365
TI  - [Fibrous bone dysplasia in the context of a McCune-Albright Syndrome].
AB  - Young male patient clinically and radiologically diagnosed of a tumour in IX
      right rib. A subsequent study with bone scintigraphy showed other areas of focal
      uptake in the skull, ribs and left trochanterian region. The biopsy of the costal
      lesion showed a fibrous dysplasia in the clinical context of a McCune-Albright
      syndrome. The convenience of using complementary imaging techniques is discussed
      to establish adequate therapeutic behavior.

PMID- 15153363
TI  - [Tumor redifferentiation in papillary thyroid carcinoma alter retinoic acid
      administration].
AB  - Male patient, 73 year old, with papillary thyroid carcinoma treated by surgery,
      131I and L-Tyroxine, with bone metastasis, detected by bone scintigraphy and CT
      scan, which negative radioiodine uptake. In order to induce tumoral
      redifferentiation, retinoic acid (70 mg/day) was administered for three months
      before 131I treatment. A radioiodine scan performed after treatment showed uptake
      in some of the bone metastasis. Nine months later, and due to disease
      progression, a second induction with retinoic acid was performed before 131I
      treatment. The radioiodine scan performed after treatment showed greater uptake
      and higher number of bone lesions than the previous scan.

PMID- 15153366
TI  - [Scintigraphic findings in a case of anterior lumbar epidural abscess].

PMID- 15153367
TI  - [Finding of primary breast cancer with PET in a woman with unknown origin tumor].

PMID- 15153368
TI  - [Isotopic studies in pediatric nephrourology].

PMID- 15153369
TI  - [Nuclear medicine within the map of public health care organization processes].

PMID- 15153371
TI  - Blood pressure position. Poor technique can distort your blood pressure readings.
      Here are some tips for doing it right.

PMID- 15153372
TI  - Cholesterol: low is good. Lower is better. PROVE IT has doctors rethinking how to
      treat high cholesterol and what's a good target.

PMID- 15153374
TI  - Putting the cuffs on chest pain. Inflatable pants may help ease angina when drugs
      and surgery aren't enough.

PMID- 15153373
TI  - Is your daily aspirin falling down on the job? Not everyone gets the full effect
      of aspirin. A new test can show if it's working for you.

PMID- 15153375
TI  - Hot-headed approach to heart disease. Anger is a normal, healthy emotion. It can
      also be bad for your heart.

PMID- 15153376
TI  - Beauty sleep for the heart.

PMID- 15153377
TI  - Get with the guidelines to survive a heart attack.

PMID- 15153378
TI  - One reason cardiologists stay busy.

PMID- 15153379
TI  - Ask the doctor. With all the news reports about fish and contamination with
      mercury or PCBs, confusion reigns supreme. Can you help?

PMID- 15153380
TI  - Gender matters: heart disease risk in women.
AB  - Heart disease is the leading cause of death among women--and one of the most
      preventable. Research is giving us new insights into how we can control our risk.

PMID- 15153381
TI  - High-flying health tips. Safeguard your health in the air with advance knowledge
      and preparation.

PMID- 15153382
TI  - Managing shingles and postherpetic neuralgia. Reactivation of the chickenpox
      virus causes severe pain and rash in older adults.

PMID- 15153383
TI  - By the way, doctor. I've been taking Prilosec for esophageal reflux. My doctor
      says I may need to take it indefinitely. Is that safe?

PMID- 15153384
TI  - By the way, doctor. I read recently about a link between antibiotics and breast
      cancer. What do you make of it?

PMID- 15153386
TI  - Picturing the prostate: Imaging techniques of today and tomorrow.

PMID- 15153385
TI  - Leisure time exercise.

PMID- 15153387
TI  - Marital stress and the heart.

PMID- 15153388
TI  - On call. I am 72 years old and have an embarrassing personal problem. I'ave had
      diabetes for 20 years and for the past 7 or 8 I've had erectile dysfunction. I
      tried Viagra as soon as it came out, but my erections were still weak. Recently I
      switched to Caverject, and I get good erections. But I don't come to climax
      anymore, although I did with Viagra. Can you explain the difference and offer
      suggestions?

PMID- 15153389
TI  - On call. I was recently diagnosed with gout. I'm feeling well with medication,
      but my doctor want me to take drugs for my cholesterol and blood pressure because
      gout will raise my risk of heart attack. I don't want to take more pills. What do
      you think?

PMID- 15153390
TI  - Women and depression. How biology and society may make women more vulnerable to
      mood disorders.

PMID- 15153391
TI  - An update on attention deficit disorder.

PMID- 15153392
TI  - Lifting spirits with a brain scan.

PMID- 15153393
TI  - Questions & answers. I've heard about the drug education program known as DARE.
      What are "harm reduction" programs, and what impact do they have on adolescent
      alcohol and drug use?

PMID- 15153394
TI  - Cholesterol limbo: How low should the bar go. Ratcheting down LDL to extra-low
      levels with high-dose statins seems to work wonders.

PMID- 15153395
TI  - Off-pump vs. conventional bypass: which is better? So far there's no clear
      winner. It may depend on the type of patient and the surgeon's ability.

PMID- 15153396
TI  - Hormone replacement, the male version. Prescriptions for testosterone have
      soared, but is the hormone safe and effective?

PMID- 15153397
TI  - Water, sodium, and potassium guidelines. Let thirst be your guide; cut back on
      sodium; and increase your potassium.

PMID- 15153399
TI  - Flower power.

PMID- 15153398
TI  - Microwaves: does the zap sap vegetables of their nutrients?

PMID- 15153400
TI  - Swiss nasal flu vaccine linked to Bell's palsy.

PMID- 15153401
TI  - By the way, doctor. I'm a 63-year-old woman with impaired fasting glucose, and
      I'd like to take Glucophage or Avandia to prevent or delay the onset of diabetes.
      My weight was well controlled until my 50s, when it started to rise. I think
      impaired fasting glucose caused the weight gain.

PMID- 15153402
TI  - By the way, doctor. My neighbor is about 80. She keeps getting run down because
      her body can't retain iron. Can you offer any advice that will help her?

PMID- 15153403
TI  - By the way, doctor. I'm 74 and in good health with no apparent heart problems.
      Because I am allergic to aspirin, it has been suggested that I take Plavix. Your
      thoughts?

PMID- 15153404
TI  - Why is it easy to control your arms ?
AB  - The complexity of our muscular systems may be regarded, not as a complication for
      the brain, but as a source of variety providing enough easily controlled movement
      recipes to do most of the things we ordinarily need to do. This simplifies the
      control task, in that if there are enough ways of moving, a recipe involving just
      a few of them can usually be found that will approximate any desired movement
      with little supervision. In particular, the presence of"redundant" degrees of
      freedom allows us to use ballistic (free swinging) movements, so that physics,
      rather than computation, accounts for much of trajectory. Computations are
      required to set up the constraints defining initializing a low-dimensional
      subsystem in such a way that a satisfactory movement exists. One theme of current
      research is that these recipes may generated by specifying the parameters of
      oscillators and spring-like components. We should expect actions to be
      represented as patchworks of recipes, each working best for some subset of
      variants of the action.

PMID- 15153405
TI  - Location versus distance in determining movement accuracy.
AB  - In a pursuit-tracking task consisting of 100 positioning movements between
      targets at 5 fixed positions, target location (proximity to the boundary of the
      task) varied independently of movement amplitude. Eighty-seven subjects performed
      12 trials of the task, with target width (at 3 levels) as a between-subject
      variable. A microprocessor system detected the location of the end-point of each
      primary movement. Movement accuracy (measured as end-point dispersion not
      constant error) varied with target location but not movement amplitude, while
      movement time varied with both factors. The effect of target width on movement
      accuracy was less consistent. The observed effects are discussed in terms of a
      mass-spring model of muscular action. It is concluded that apart from having
      important consequences for the design of positioning experiments, these results
      call into question information-processing and impulse-variability theories which
      implicate movement amplitude in determining movement accuracy, and support
      theories which emphasize target location.

PMID- 15153406
TI  - Simple reaction time as a function of response complexity: memory drum theory
      revisited.
AB  - The prediction emanating from memory drum theory (Henry & Rogers, 1960') that
      simple reaction time (SRT) increases as a response becomes more complex (i.e.,
      increases in number of movement parts) was investigated. Experiments 1 (N = 20)
      and 3 (N = 16) indicated that SRT was longer for responses consisting of two and
      three parts than it was for a one-part response and this may be interpreted as
      support for the prediction. Failing to support the prediction, however, was the
      finding that SRT was essentially the same for responses consisting of two and
      three parts. This may not be too damaging to the theory because it could simply
      be reflecting an upper limit in terms of numbers of parts or response duration
      for causing an increase in SRT. Experiments 2 (N = 20) and 3 revealed an SRT
      effect between two responses that were supposed to be equal in complexity. At
      first, this finding appeared to be contrary to the prediction, but it may be
      interpreted as support for it because one of the responses defined as having one
      movement part could actually have had two

PMID- 15153407
TI  - Preprogramming, programming and reprogramming of aimed hand movements as a
      function of age.
AB  - The present experiments were conducted to investigate the relationship between
      age and the response programming operations underlying the execution of a
      ballistic motor act. In an initial experiment, two separate age groups of female
      subjects (mean ages of 21.9 and 69.1 years) performed aimed-movements of the
      right hand and arm in one of two movement directions (left or right), under
      preprogramming, programming, and reprogramming conditions. These operations were
      examined by providing advance information about the direction of an impending
      movement and manipulating the degree of correspondence between the advance
      information and a subsequent reaction signal. The results indicated that subjects
      in the older age group reacted and moved more slowly than subjects in the younger
      age group, however, there was no interaction between age and the three response
      programming conditions. Such findings indicated that the basic operational
      characteristics of these processes remain unaffected with advancing chronological
      age. Also, irrespective of age and response programming condition, responses to
      the right were initiated faster than responses to the left. This difference was
      especially accentuated for reprogramming. A second experiment, using a new
      stimulus-response mapping, replicated the left-right difference in initiation
      time; this difference was reversed when the left hand was used to execute the
      designated movement, indicating that this finding is indeed a response
      programming phenomenon. Further discussion focused on the possible operations
      underlying reprogramming.

PMID- 15153408
TI  - Distance and movement time effects on the timing of agonist and antagonist
      muscles: a test of the impulse-timing theory.
AB  - The experiment examined the effects of movement time (MT) and distance on the
      timing at electromyographic (EMG) activity from an agonist and antagonist muscle
      during rapid, discrete elbow movements in the horizontal plane. According to
      impulse-timing theory (Wallace, 1981) MT, not distance moved, should have a
      pronounced effect on the timing of EMG activity (duration of initial agonist and
      antagonist burst and time to onset of initial antagonist burst). The levels of MT
      were 100 and 160 msec and the levels of distance were 27 degrees and 45 degrees
      of elbow flexion. In general support of impulse-timing theory, the results of the
      three EMG timing measures showed that MT had a more pronounced effect on these
      measures than distance. In addition, the timing of EMG activity in relation to
      total MT remained fairly consistent across the four MT-distance conditions.

PMID- 15153409
TI  - Interaction of afferent and efferent signals underlying joint position sense:
      empirical and theoretical approaches.
AB  - A model of joint position sense is considered based on the concept that central
      motor commands are adequately expressed in terms of shifts of the so-called
      invariant length-tension characteristics for agonist and antagonist muscles. The
      main points of this concept are discussed to clarify them and to prevent
      misunderstanding. The basic idea of the model is that the efferent copy of the
      central motor commands plays the role of a reference frame for evaluation of
      afferent proprioceptive discharges. An experiment with reproduction of
      constrained movements was performed in order to investigate the influence of
      voluntary flexor or extensor muscle tension on position sense in the elbow joint.
      The results demonstrate adequate perception of joint position on the background
      of voluntary muscle tension and thus are quite consistent with the model. The
      role of afferent and efferent signals in position sense is discussed with special
      reference to views expressed recently by different authors. The interrelation
      between position sense and sense of effort is considered, based on a concept of
      senso-motor space.

PMID- 15153410
TI  - Analysis of "invariant characteristics" in the motor control of down's syndrome
      and normal subjects.
AB  - Following Asatryan and Fei'dman (1965), two experiments were conducted to
      describe the so-called invariant mechanical properties underlying movement
      control in Down's syndrome and normal subjects. The invariant characteristic is a
      curve on a graph of joint torque versus joint angle. The task required subjects
      to maintain a steady joint angle against an external load (torque). Torque was
      systematically changed via partial unloading in order to obtain torque by length
      (joint angle) functions at three separate initial joint angles. Instructions
      required subjects "not to intervene" when unloading occurred in Experiment 1 and
      to "tense" their muscles prior to unloading in Experiment 2. Both normal and
      Down's syndrome groups revealed systematic torque by length functions that might
      be expected according to a simple mass-spring system model. Although the gross
      organization of movement in Down's syndrome subjects was nearly the same as
      normals, important differences between the two groups were found. Down's syndrome
      subjects revealed underdamped motions relative to normals (as shown by
      differences in the degree of oscillation about the final equilibrium position)
      and were less able to regulate stiffness (as shown by differences in slope of the
      torque by angle functions in Experiment 2). We promote the notion that damping
      and stiffness may be sensitive indices of hypotonia-the most common description
      of neuromuscular deficiency in Down's syndrome

PMID- 15153411
TI  - Movement cue reproduction under preselection.
AB  - A series of three experiments was undertaken to determine the role of prior
      knowledge of different movement cues in the preselection effect. Experiments 1
      and 2 examined the singular and combinative role of location and extent cues
      under both preselected and constrained conditions. The third experiment provided
      a framework for evaluating the sources of informations which may contribute to
      the preselection phenomenon. In experiments 1 an 2, the results suggest the
      advantage of preseleted over constrained movement was constant across movement
      cues. The second experiment demonstrated that the dual cue condition was superior
      to location alone and extent alone in both accuracy and consistency. Finally, the
      third experiment indicated that prior knowledge (strategy) was the primary
      variable responsible for the preselection effect.

PMID- 15153412
TI  - Memory drum theory: alternative tests and explanations for the complexity effects
      on simple reaction time.
AB  - Two experiments investigated the memory drum theory's prediction (Henry & Rogers,
      1960) that simple reaction time (SRT) increased with the complexity of the
      response to be initiated. Experiment 1 (N = 9) matched the Experiment 1, Group 1,
      SRT condition described by Henry and Rogers. Results of Experiment 1 replicated
      those of Henry and Rogers and indicated that the memory drum theory's prediction
      of increased SRT as a function of increased complexity of response was tenable.
      Experiment 2 (N = 11) tested the effects of anatomical unit, extent and target
      size on SRT, premotor time, and motor time. The results supported the contention
      that alternative explanations for SRT were possible. With complexity constant,
      increases in anatomical unit lead to increases in SRT, but only in the motor time
      component which indicated electromechanical rather than neuromotor program
      delays. It is proposed that the increased motor time could be explained by
      peripheral events such as the duration maximum torque must be applied by the
      agonist muscle(s) to generate the angular acceleration required to initiate rapid
      movement. SRT, premotor time, and motor time increased when target size was
      reduced from 6.35 cm to 79 cm. The increased premotor time could be a function of
      the determining of new equilibrium points for the elbow joint during response
      initiation. No effects on SRT were observed for extent.

PMID- 15153413
TI  - Developmental differences in response processing.
AB  - Three age groups (kindergartners, fourth graders, and adults) were compared in
      their processing of response decisions in a two-choice reaction time task.
      Manipulation of spatial stimulus-response compatibility resulted in age-related
      differential effects on reaction time performance. For the younger children,
      selecting the appropriate response for an incompatibly paired stimulus light
      required proportionately longer processing time than for older subjects. Similar
      results were not found for performance under varying levels of response
      discriminability.

PMID- 15153415
TI  - The "normal" endocrine cell of the gut: changing concepts and new evidences.
AB  - The endocrine cells of the gut are a highly specialized mucosal cell
      subpopulation. Within the gastrointestinal tract at least 14 different cell types
      produce a wide range of hormones with a specific regional distribution. The gut
      endocrine cells belong to the diffuse endocrine system. These cells present two
      regulated pathways of secretion characterized by large dense core vesicles (LDCV)
      and synaptic-like microvesicles (SLMV). Gut endocrine cells are recognized by the
      expression of several "general" markers, including the LDCV marker chromogranin A
      and the SLMV marker synaptophysin, in addition to the cytosolic markers neuron
      specific enolase and protein gene product 9.5. The expression of different
      hormones identifies specific cell types. The gut endocrine cells are reputed to
      be terminally differentiated and incapable of proliferation. However, some data
      suggest that the number of gut endocrine cells may adapt in response to tissue
      specific physiological stimuli. Gut endocrine cell differentiation appears to
      follow a "constitutive" tissue-specific pathway, which may be disrupted and
      investigated by genetic manipulation in mice. It is suggested that endocrine cell
      homeostasis is maintained by the entry of new endocrine-committed cells along the
      differentiation pathway and that such intermediate cells may be sensitive to
      physiological stimuli as well as transforming agents.

PMID- 15153416
TI  - The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO
      classification.
AB  - Although well established in medical terminology, the term carcinoid is no longer
      adequate to cover the entire morphological and biological spectrum of neoplasms
      of the disseminated neuroendocrine cell system. Therefore, instead of carcinoid,
      the WHO classification published in 2000 uses the general terms neuroendocrine
      tumor and neuroendocrine carcinoma. In this review a classification of
      gastroenteropancreatic neuroendocrine tumors based on the WHO criteria is
      described. We also classify and comment on the most important tumor entities. On
      the basis of localization and of various morphological and biological criteria,
      we distinguish between benign neuroendocrine tumors, tumors with uncertain
      malignant potential, and tumors showing low-grade and high-grade malignancy.

PMID- 15153417
TI  - Transcription factors in islet development and physiology: role of PDX-1 in beta
      cell function.
AB  - Differentiation of early foregut endoderm into pancreatic endocrine and exocrine
      cells depends on a cascade of gene activation events controlled by various
      transcription factors. The first molecular marker identified that specifies the
      early pancreatic epithelium is the homeodomain-containing transcription factor
      PDX-1. Its absence in mice and humans during development leads to agenesis of the
      pancreas. Later, it becomes restricted primarily to beta cells where it regulates
      the expression of beta cell-specific genes, and, most importantly, mediates the
      glucose effect on insulin gene transcription. Although exposure of beta cells to
      high glucose concentrations for relatively short periods stimulates insulin gene
      expression, chronic exposure has adverse effects on many beta-cell functions,
      including insulin gene transcription. These events appear to correlate with pdx-1
      gene expression and its ability to bind the insulin gene. We consider that loss
      of PDX-1 function or altered pdx-1 gene expression due to mutations or functional
      impairment of transcription factors controlling its expression can lead to
      diabetes.

PMID- 15153418
TI  - Transgenic tagging defining pancreatic pedigrees.
AB  - In this review, analyses of the ontogenetic relations between the different
      pancreatic cell types are summarized. Lineage analyses allow identification of
      progenitor cells from which mature cell types differentiate. This knowledge is
      highly relevant for future cell replacement therapies in diabetic patients,
      helping to define the identity of putative pancreatic stem cells.

PMID- 15153419
TI  - EG-VEGF: a novel mediator of endocrine-specific angiogenesis, endothelial
      phenotype, and function.
AB  - Angiogenesis is the focus of therapeutic efforts to promote new vessel
      development in damaged tissues. Conversely, inhibiting endothelial cell growth
      and survival is a strategy to treat various proliferative diseases. Much evidence
      indicates that VEGF is a key mediator of angiogenesis. Recently, a novel
      angiogenic mitogen with tissue-specific expression and target selectivity was
      characterized. Human endocrine gland derived vascular endothelial growth factor
      (EG-VEGF) is selectively expressed in steroidogenic glands and promotes growth of
      endocrine gland endothelium. The identification of tissue-selective angiogenic
      factors raises the possibility that other secreted molecules in this class exist.
      The potential advantage of tissue-specific angiogenic therapeutics may be the
      reduction of systemic side effects. Additionally, these peptides or their
      receptors may be attractive targets for inhibition in several disorders.

PMID- 15153420
TI  - Multitasking in tumor progression: signaling functions of cell adhesion
      molecules.
AB  - Approximately 90% of all cancer deaths arise from metastasis formation. Hence,
      understanding the molecular mechanisms underlying tumor progression, local
      invasion, and the formation of tumor metastases represents one of the great
      challenges in exploratory cancer research. Recent experimental results indicate
      that changes in cell adhesion play a critical role in tumor progression. Cell
      adhesion molecules of varying classes and functions, including cadherins, cell
      adhesion molecules of the immunoglobulin family (Ig-CAMs), CD44, and integrins,
      can interact with and modulate the signaling function of receptor tyrosine
      kinases (RTKs). Conversely, signaling by RTKs can directly affect the adhesive
      function of adhesion molecules. Loss of E-cadherin and gain of mesenchymal
      cadherin function as well as changes in the expression of Ig-CAMs during the
      progression of many cancer types exemplify such functional implicatons: cell
      adhesion molecules not only define a tumor cell's adhesive repertoire, but also
      directly influence classic signal transduction pathways, thereby modulating the
      metastatic behavior of tumor cells.

PMID- 15153421
TI  - Molecular imaging of tumor angiogenesis.
AB  - Advances in imaging provide new insights into the pathophysiology of many
      diseases. Established imaging technologies such as MRI, CT, PET, and ultrasound
      are routinely applied to determine features of tumor blood vessels that
      distinguish them from normal blood vessels. These techniques yield information on
      blood flow, blood volume, and vessel permeability. Often, an intravenously
      injected imaging contrast agent without affinity to a specific target structure
      is applied to enable detection of malignant lesions. One of the emerging
      innovations in diagnostic imaging is the evolution of molecular imaging
      techniques. Molecular imaging is a noninvasive approach to determine the
      expression of indicative marker molecules of the tumor angiogenesis process.
      Meanwhile, this approach has been established for all imaging modalities and may
      further improve sensitivity of diagnostic tumor imaging. Another goal is to
      provide information with respect to drug treatment monitoring and therapeutic
      vascular targeting strategies.

PMID- 15153422
TI  - Molecular regulation of lymphangiogenesis.
AB  - The lymphatic vascular system is necessary for the return of extravasated
      interstitial fluid and macromolecules to the blood circulation, for immune
      defense, and for the uptake of dietary fats. Impaired functioning of lymphatic
      vessels results in lymphedema, whereas tumor-associated lymphangiogenesis may
      contribute to the spread of cancer cells from solid tumors. Recent studies have
      identified lymphatic molecular markers and growth factors necessary for
      lymphangiogenesis. In particular, lymphatic endothelial receptor tyrosine kinase
      VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting
      lymphatic vascular growth both during development and in pathological conditions.
      Isolation of pure cultures of lymphatic and blood vascular endothelial cells and
      systematic characterization of their transcriptomes provide useful cell culture
      models and novel potential vascular markers and offer further insights into the
      lymphatic vascular biology. Ectopic expression of the lymphatic endothelial
      specific homeobox transcription factor Prox1 in blood endothelial cells results
      in a shift in the gene expression profile towards the lymphatic endothelial
      phenotype, demonstrating the plasticity of endothelial cells and offering the
      possibility of transcriptional reprogramming of vascular endothelial cells for
      future therapeutic applications.

PMID- 15153423
TI  - Regulation of insulin secretion: insights from engineered beta-cell lines.
AB  - Abnormalities in insulin secretion are involved in a number of diseases,
      including type 1 and type 2 diabetes, persistent hyperinsulinemic hypoglycemia of
      infancy, and insulinoma. Understanding the mechanisms that regulate insulin
      secretion may allow the development of new therapies for these diseases as well
      as contribute to our ability to engineer insulin-producing cells for cell
      replacement therapy of type 1 diabetes. Glucose phosphorylation in beta-cells has
      been viewed as a key regulatory event in coupling insulin secretion to
      extracellular glucose concentrations. Work with transformed rodent beta-cell
      lines as well as recent findings from human progenitor cells induced to
      differentiate into insulin-producing cells has provided new insights into the
      role of glucose phosphorylating enzymes in the regulation of insulin secretion.

PMID- 15153424
TI  - Molecular mechanisms of gastrin-dependent gene regulation.
AB  - The peptide hormone gastrin is the key regulator of gastric acid secretion.
      Gastrin exerts its effects as acid secretagogue through functional activation of
      gastric enterochromaffin-like (ECL) cells, which control acid secretion through
      biosynthesis and release of histamine. In ECL cells, concerted activation of
      histidine decarboxylase (HDC), vesicular monoamine transporter 2 (VMAT2), and
      chromogranin A (CgA) genes by gastrin is a prerequisite for proper acid control.
      To elucidate the molecular pathways underlying gastrin-dependent control of ECL
      cell genes, we recently analyzed the signaling cascades, regulatory promoter
      elements, and transcription factors mediating the transcriptional effects of
      gastrin. Our studies identified the Raf>MEK1>ERK 1/-2 kinase module as the common
      signaling pathway mediating gastrin-dependent ECL cell gene transcription. In
      contrast to this uniform signaling cascade, pronounced heterogeneity was detected
      between cis- and trans-activating regulatory factors conferring gastrin
      responsiveness. The molecular diversity of transcription factors and regulatory
      enhancer elements transmitting gastrin-triggered gene transcription offers the
      molecular basis for synergistic, but differential, regulation of HDC, VMAT2, and
      CgA genes during a secretory challenge of ECL cells by gastrin and possibly other
      acid secretagogues.

PMID- 15153425
TI  - REST and peace for the neuronal-specific transcriptional program.
AB  - Despite a genetic homogeneity, cells in multicellular organisms are structurally
      and functionally heterogeneous. The diversity of cell phenotypes exists due to
      differential transcriptional programs precisely regulated by specific nuclear
      factors and induced upon differentiation. The differences in gene expression
      programs arise during development and become heritable during cell proliferation.
      Over the last few years, research has focused on three molecular mechanisms that
      mediate epigenetic phenomena: DNA methylation, histone modification, and
      formation of specialized nuclear domains or territories. All of these processes
      are dynamic and tightly linked to the organism's development. Here we review
      advances in understanding the significance of epigenetic mechanisms in the
      establishment and maintenance of the specialized transcriptional program. We
      project the accumulated knowledge onto the delineation of the molecular
      mechanisms by which central nervous system-specific genes are expressed in the
      nervous system and repressed in other tissues.

PMID- 15153426
TI  - Molecular signaling of somatostatin receptors.
AB  - Somatostatin is a neuropeptide family that is produced by neuroendocrine,
      inflammatory, and immune cells in response to different stimuli. Somatostatin
      acts as an endogenous inhibitory regulator of various cellular functions
      including secretions, motility, and proliferation. Its action is mediated by a
      family of G-protein-coupled receptors (called sst1-sst5) that are widely
      distributed in the brain and periphery. The five receptors bind the natural
      peptides with high affinity, but only sst2, sst5, and sst3 bind the short
      synthetic analogs used to treat acromegaly and neuroendocrine tumors. This review
      covers the current knowledge in somatostatin receptor biology and signaling.

PMID- 15153427
TI  - Immunohistochemical localization of somatostatin receptor sst2A in human gut and
      lung tissue: possible implications for physiology and carcinogenesis.
AB  - Many neuroendocrine gastrointestinal and lung tumors express sst2A somatostatin
      receptors. Because the cellular location of sst2A in the corresponding non
      neoplastic tissue is unknown, we searched for sst2A immuno-reactive cells and
      characterized their type in these tissues using a highly specific sst2A antibody
      (R2-88). Epithelial sst2A cells, identified as neuroendocrine, gastrin-producing
      cells, were found in large numbers in the antrum and the duodenum, but not in the
      gastric corpus. They were also present in the proximal jejunum, rarely noted in
      the distal jejunum and ileum, and absent in the large intestine and the appendix
      vermiformis. Moreover, sst2A cells were found abundantly in the neural plexus.
      sst2A receptors on antral gastrin cells could mediate somatostatin inhibition on
      gastrin secretion, whereas those in the neural plexus could mediate somatostatin
      effects on motility and ion transport in the lower gastrointestinal tract. Rare
      sst2A cells in bronchi and bronchioles located basally and parabasally in the
      gastrointestinal epithelium were detected that could represent stem/progenitor
      cells. It is currently not clear whether and which of the identified sst2A cells
      are at the origin of sst2A-positive neuroendocrine gut or lung tumors.

PMID- 15153428
TI  - Ca(2+) channel properties in neuroendocrine tumor cell cultures investigated by
      whole-cell patch-clamp technique.
AB  - Neuroendocrine tumor (NET) cells of the gastroenteropancreatic system express a
      variety of voltage-operated Ca(2+) channels (VOCCs). In addition, NET cells
      release hormones and biogenic amines in distinct patterns, leading to typical
      hypersecretion syndromes. Interestingly, these patterns depend on the primary
      location of the NET. The aim of this study was to investigate a possible link
      between clinically distinct entities of NETs and specific properties of VOCCs.
      Using whole-cell patch-clamp technique, electrophysiological data were obtained
      from permanent NET cell cultures as well as from primary cultivated NET cells
      from foregut and midgut tumors. Definite Ca(2+) channel characteristics were
      analyzed by a color-coding method. As a result, we could demonstrate specific
      Ca(2+) channel characteristics in NET cells from midgut tumors that were not
      found in NET cells from a foregut location. This may be important functionally
      with respect to different cell biological functions of NET cells. In summary,
      clear differences exist in the VOCC pattern in NET cells from foregut versus
      midgut. This may be functionally relevant in the hypersecretion syndrome
      predominantly found in foregut NETs. Therefore, these data on the characteristics
      of VOCCs could be useful in the development of a novel therapy for NET disease;
      for example, specific VOCC subtype modulators may help.

PMID- 15153429
TI  - Regulators of neurite outgrowth: role of cell adhesion molecules.
AB  - Neuronal differentiation is a fundamental event in the development of the nervous
      system as well as in the regeneration of damaged nervous tissue. The initiation
      and guidance of a neurite are accomplished by positive (permissive or
      attractive), negative (inhibitory or repulsive), or guiding (affecting the
      advance of the growth cone) signals from the extracellular space. The signals may
      arise from either the extracellular matrix (ECM) or the surface of other cells,
      or be diffusible secreted factors. Based on this classification, we briefly
      describe selected positive, negative, and guiding signaling cues focusing on the
      role of cell adhesion molecules (CAMs). CAMs not only regulate cell-cell and cell
      ECM adhesion "mechanically," they also trigger intracellular signaling cascades
      launching neurite outgrowth. Here, we describe the structure, function, and
      signaling of three key CAMs found in the nervous system: N-cadherin and two Ig
      CAMs, L1 and the neural cell adhesion molecule NCAM.

PMID- 15153430
TI  - Cadherin switch in tumor progression.
AB  - The loss of E-cadherin expression or function in epithelial carcinomas has long
      been thought as a primary reason for disruption of tight epithelial cell-cell
      contacts and release of invasive tumor cells from the primary tumor. Indeed, E
      cadherin serves as a widely acting suppressor of invasion and growth of
      epithelial cancers, and its functional elimination represents a key step in the
      acquisition of the invasive phenotype for many tumors. Recent evidence indicates,
      however, that in addition to the loss of the "invasion-suppressor" E-cadherin,
      another adhesion molecule, N-cadherin, becomes upregulated in invasive tumor cell
      lines. N-cadherin was shown to be present in the most invasive and
      dedifferentiated breast cancer cell lines, and its exogenous expression in tumor
      cells induces a scattered morphology and heightened motility, invasion, and
      metastasis. N-cadherin cooperates with the FGF receptor, resulting in signals
      that lead to the up-modulation of MMP-9 and, hence, cellular invasion. In
      addition to a signaling function in metastasis, N-cadherin probably also supports
      the systemic dissemination of tumor cells by enabling circulating tumor cells to
      associate with the stroma and the endothelium at distant sites. Here, we
      summarize the various aspects of the E- to N-cadherin switching in epithelial
      carcinomas and its potential impact on metastatic progression.

PMID- 15153431
TI  - Lipid rafts and apical membrane traffic.
AB  - Lipid rafts are dynamic assemblies floating freely in the surrounding membranes
      of living cells. This membrane heterogeneity provides a useful concept for
      understanding processes as diverse as cell polarity, signal transduction, and
      membrane sorting. Individual rafts are small entities containing thousands of
      lipids but only a few proteins. Regulation of raft association and size is an
      elementary feature of interactions at the molecular level. By clustering small
      rafts into a bigger platform, proteins are brought together for modification.
      Oligomerization might transform a monomeric weakly raft-associated protein into
      an assembly with higher raft affinity. Lectins are multivalent glycoprotein
      binding proteins and are likely to be key players in mediating the clustering of
      rafts in vivo. Glycosylation-dependent surface delivery in a polarized fashion is
      a feature conserved across evolution, and we expect lectins to be at the heart of
      the molecular machinery responsible for lipid raft delivery to the cell surface.
      Currently, we are evaluating candidate proteins by affinity chromatography,
      proteomics, and RNA interference.

PMID- 15153432
TI  - Principles of exocytosis and membrane fusion.
AB  - Exocytosis is a ubiquitous process occurring in every eukaryotic cell including
      processes as diverse as membrane expansion during growth and the highly regulated
      release of neurotransmitter from neurons. Work during the past decade has
      established that exocytotic membrane fusion is mediated by members of conserved
      protein families including Rab proteins and SNAREs. SNAREs are probably
      catalyzing membrane fusion, and major progress has been made in unraveling their
      molecular mechanism. In contrast, less is known about regulatory mechanisms.
      Here, a brief overview is given about the current state of knowledge, focusing on
      SNAREs involved in neuronal exocytosis.

PMID- 15153433
TI  - Serotonin secretion by human carcinoid BON cells.
AB  - BON cells are human carcinoid cells that secrete serotonin (5-HT) and various
      peptides. Secretion of [(3)H]5-HT by cell cultures was investigated.
      Acetylcholine (Ach) stimulated secretion through a somatostatin-sensitive
      muscarinic pathway, whereas isoproterenol was inefficient. [(3)H]5-HT secretion
      also was induced by Ca(2+) in the presence of the ionophore A-23187 or after
      digitonin permeabilization. These two processes were insensitive to
      stomatostatin. Ba(2+) induced an efficient somatostatin-sensitive [(3)H]5-HT
      secretory response. Secretion also was analyzed at the single-cell level, using
      carbon fiber amperometry and evanescent-field fluorescence microscopy, after
      labeling the secretory vesicles by transfection of the cells with a NPY-GFP
      construct. Both techniques revealed slow kinetics of secretory responses,
      suggesting that ready-to-fuse vesicles do not accumulate in these cells. Single
      secretory vesicles were imaged either in resting conditions or after addition of
      Ca(2+) ions to digitonin-permeabilized cells. The three-dimensional movements of
      the vesicles before exocytosis were analyzed. The mean velocity of vesicles that
      released their content was lower than that of silent ones. Even in the case of
      mobile vesicles, exocytosis often was preceded by a period of arrest lasting at
      least 15 seconds, consistent with a docking/priming step.

PMID- 15153434
TI  - Molecular pathology of the MEN1 gene.
AB  - Multiple endocrine neoplasia type 1 (MEN1), among all syndromes, causes tumors in
      the highest number of tissue types. Most of the tumors are hormone producing
      (e.g., parathyroid, enteropancreatic endocrine, anterior pituitary) but some are
      not (e.g., angiofibroma). MEN1 tumors are multiple for organ type, for regions of
      a discontinuous organ, and for subregions of a continuous organ. Cancer
      contributes to late mortality; there is no effective prevention or cure for MEN1
      cancers. Morbidities are more frequent from benign than malignant tumor, and both
      are indicators for screening. Onset age is usually earlier in a tumor type of
      MEN1 than of nonhereditary cases. Broad trends contrast with those in
      nonneoplastic excess of hormones (e.g., persistent hyperinsulinemic hypoglycemia
      of infancy). Most germline or somatic mutations in the MEN1 gene predict
      truncation or absence of encoded menin. Similarly, 11q13 loss of heterozygosity
      in tumors predicts inactivation of the other MEN1 copy. MEN1 somatic mutation is
      prevalent in nonhereditary, MEN1-like tumor types. Compiled germline and somatic
      mutations show almost no genotype/phenotype relation. Normal menin is 67 kDa,
      widespread, and mainly nuclear. It may partner with junD, NF-kB, PEM, SMAD3,
      RPA2, FANCD2, NM23beta, nonmuscle myosin heavy chain II-A, GFAP, and/or vimentin.
      These partners have not clarified menin's pathways in normal or tumor tissues.
      Animal models have opened approaches to menin pathways. Local overexpression of
      menin in Drosophila reveals its interaction with the jun-kinase pathway. The
      Men1+/- mouse has robust MEN1; its most important difference from human MEN1 is
      marked hyperplasia of pancreatic islets, a tumor precursor stage.

PMID- 15153435
TI  - Molecular genetics of gastroenteropancreatic endocrine tumors.
AB  - To elucidate the molecular background of sporadic gastroenteropancreatic
      endocrine tumors, several investigations into chromosomal alterations and allelic
      imbalances have identified several chromosomal regions of interest. These regions
      might harbor candidate genes important in tumor development and progression.
      However, only a small number of genes have been thoroughly analyzed, and only
      very few were shown to be altered in a substantial subset of tumors. Therefore,
      we are far from understanding the molecular mechanisms of tumor initiation and
      progression in gastroenteropancreatic endocrine tumors, although some "molecular
      patterns" are currently emerging. In this review, chromosomal alterations, that
      is, allelic losses and gene mutations, identified in gastroenteropancreatic
      endocrine tumors are briefly summarized. Molecular differences among various
      subtypes of gastroenteropancreatic endocrine tumors are highlighted in view of
      their role as indicators of separate genetic pathways.

PMID- 15153436
TI  - Cyclin D1 in human neuroendocrine: tumorigenesis.
AB  - Human neuroendocrine tumors exhibit unique biological properties, and defining
      the molecular genetic alterations that underlie these distinctive features
      remains an important challenge. In addition to the MEN1 tumor suppressor gene,
      the cyclin D1 oncogene has demonstrated a role in the pathogenesis of parathyroid
      and gastroenteropancreatic neuroendocrine tumors. Up-regulation of cyclin D1 is
      observed early in tumor formation, implying a possible role in tumor initiation.
      Overexpression of cyclin D1 in the parathyroid glands of mice resulted in the
      tandem regulation of cellular proliferation and hormonal secretion, a feature
      intrinsic to neuroendocrine tumors.

PMID- 15153437
TI  - Analysis of molecular pathways in neuroendocrine cancers of the
      gastroenteropancreatic system.
AB  - Neuroendocrine gastroenteropancreatic (GEP) tumors are rare and present with
      variable clinical syndromes. So far, there are no detailed studies concerning the
      molecular pathogenesis of sporadic GEP tumors. In our study, GEP tumors from 29
      patients were assessed for microsatellite instability, aberrant promoter
      methylation, and LOH of various tumor suppressor genes. All tumors were
      microsatellite stable. One tumor showed LOH close to the APC locus, one tumor had
      an allelic loss near the hMLH1 gene, and one tumor showed hypermethylation of the
      hMLH1 promoter. Interestingly, none of the tumors was aberrantly methylated at
      the p16 promoter. However, 13 of 20 successfully amplified tumors (65%) were
      hypermethylated at the APC promoter. Of the hypermethylated tumors, none showed
      LOH of either the hMLH1 or the APC gene. The current study is the first report
      demonstrating that aberrant methylation of the APC promoter is strongly involved
      in the molecular tumorigenesis of neuroendocrine GEP tumors. MSI does not seem to
      be involved in the pathogenesis of these cancers. Further studies are required to
      investigate the role of hypermethylation in neuroendocrine GEP tumors and to
      further elucidate the role of the APC pathway in these tumors.

PMID- 15153438
TI  - Programmed cell death protein 4 (PDCD4) acts as a tumor suppressor in
      neuroendocrine tumor cells.
AB  - PDCD4 is a new tumor suppressor gene. In the current study, we show that
      overexpression of PDCD4 in carcinoid cells results in inhibition of cell
      proliferation. This is most likely caused by a PDCD4-induced downregulation of
      carbonic anhydrase type II which catalyzes the production of bicarbonate, a
      fundamental substrate for many cellular pathways.

PMID- 15153439
TI  - Survival and clinical outcome of patients with neuroendocrine tumors of the
      gastroenteropancreatic tract in a german referral center.
AB  - Neuroendocrine tumors (NETs) are rare neoplasms. Approximately 75% of all cases
      manifest in the gastroenteropancreatic (GEP) system. Because of the low incidence
      of NETs, limited data about the clinical outcome and prognostic variables are
      available. In an attempt to identify prognostic parameters, we investigated the
      distribution of primary tumors, pattern of metastasis formation, clinical
      presentation, histological classification, and outcome of therapeutic
      interventions in a large patient cohort cared for in a German referral center. In
      254 patients with GEP-NETs, the primary tumor was of foregut, midgut, or hindgut
      origin in 44.1% (28.7% pancreas), 43.7% (34.7% jejunoileum), and 4.3%,
      respectively. No primary tumor was found in 7.9%. Metastases occurred
      preferentially in lymph nodes and the liver. The overall 5-year survival rate was
      57.1%. In the absence or presence of metastases at initial diagnosis the 5-year
      survival rate was 80.0% and 51.7%, respectively. The 5-year survival rate was
      related to the localization of the primary and was 75.0% and 42.9% for
      jejunoileal and pancreatic tumors, respectively. The size of the primary tumor
      (<2 cm) and histological grading as low-grade malignant were both associated with
      a significantly longer survival. Surgery with curative intent was attempted in
      141 patients. However, an R(0) resection was achieved in only 66.0% of these
      patients. Five-year survival rate in the latter group was significantly higher
      (77.3%) as compared with all surgical patients (55.4%). Long-term tumor-free
      survival was obtained in only 53.7% of successfully resected patients. Palliative
      medical treatment, either with chemotherapy (i.e., especially for foregut NETs)
      or biotherapy (especially for midgut NETs), was only moderately effective for
      both therapeutic regimens.

PMID- 15153440
TI  - Peptide receptor radionuclide therapy.
AB  - On their plasma membranes, cells express receptor proteins with high affinity for
      regulatory peptides, such as somatostatin. Changes in the density of these
      receptors during disease, for example, overexpression in many tumors, provide the
      basis for new imaging methods. The first peptide analogues successfully applied
      for visualization of receptor-positive tumors were radiolabeled somatostatin
      analogues. The next step was to label these analogues with therapeutic
      radionuclides for peptide receptor radionuclide therapy (PRRT). Results from
      preclinical and clinical multicenter studies already have shown an effective
      therapeutic response when using radiolabeled somatostatin analogues to treat
      receptor-positive tumors. Infusion of positively charged amino acids reduces
      kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor
      positive tumors, such as medullary thyroid carcinoma, radiolabeled minigastrin
      analogues currently are being successfully applied. The combination of different
      therapy modalities holds interest as a means of improving the clinical
      therapeutic effects of radiolabeled peptides. The combination of different
      radionuclides, such as (177)Lu- and (90)Y-labeled somatostatin analogues, to
      reach a wider tumor region of high curability, has been described. A variety of
      other peptide-based radioligands, such as bombesin and NPY(Y(1)) analogues,
      receptors for which are expressed on common cancers such as prostate and breast
      cancer, are currently under development and in different phases of (pre)clinical
      investigation. Multireceptor tumor targeting using the combination of bombesin
      and NPY(Y(1)) analogues is promising for scintigraphy and PRRT of breast
      carcinomas and their lymph node metastases.

PMID- 15153441
TI  - PET in the diagnosis of neuroendocrine tumors.
AB  - For general oncological imaging, positron emission tomography (PET) using
      [18F]fluoro-deoxy-glucose (FDG) has evolved as a powerful functional imaging
      modality. Unfortunately, FDG-PET has not been as advantageous for imaging
      gastropancreatic neuroendocrine tumors, and only tumors with high proliferative
      activity and low differentiation have shown an increased FDG uptake. Therefore,
      the 11C-labeled amine precursors L-dihydroxyphenylalanine and 5-hydroxy-L
      tryptophan (5-HTP) were developed for PET imaging of these tumors. Because of the
      higher tumor uptake of the latter tracer in a study of patients with endocrine
      pancreatic tumors, 11C-5-HTP was chosen for further evaluation. In comparative
      studies of patients with carcinoids and endocrine pancreatic tumors, 5-HTP-PET
      proved better than CT and somatostatin receptor scintigraphy for tumor
      visualization, and many small, previously overlooked lesions were diagnosed by
      11C-5-HTP-PET. The strong correlation found during medical treatment between the
      changes in the transport rate constant at repeated PET and those of U-HIAA
      indicates the possible use of 11C-5-HTP-PET also for therapy monitoring. By
      premedication of patients with Carbidopa orally before PET examination, in order
      to block the aromatic amino acid decarboxylase enzyme, the decarboxylation rate
      of 11C-5-HTP was decreased, leading to a higher tumor uptake and a considerably
      lower urinary radioactivity concentration.

PMID- 15153442
TI  - Somatostatin receptor targeting for tumor imaging and therapy.
AB  - Somatostatin receptors and their ligands constitute the prototype targeting
      system for contrast-enhanced detection and radiotherapy of cancer. Radiolabeled
      synthetic analogs of somatostatin have been successfully used in routine
      molecular imaging of primary gastroenteropancreatic neuroendocrine tumors and
      their metastases for more than 15 years. Likewise, analog conjugates for
      radiation therapy have been developed and have been under clinical trial for
      several years. The vast amount of knowledge accumulated by both basic and
      clinical science has made the somatostatin/somatostatin receptor system a popular
      model for new targeting strategies in imaging and therapy. Among those, the use
      of near-infrared fluorescent dye-peptide conjugates for the detection of tumors
      by endoscopy, mammography, or intraoperative imaging is one of the most
      promising. This article reviews recent developments in the field and discusses
      concepts for receptor-targeted molecular imaging and therapy.

PMID- 15153443
TI  - Liver transplantation for treatment of metastatic neuroendocrine tumors.
AB  - Liver transplantation can be considered a therapeutic option for patients with
      neuroendocrine tumors only metastatic to the liver. Important selection criteria
      are well-differentiated tumors and a low proliferation rate (Ki67 <10%). In this
      series, orthopic liver transplantation offered good relief of symptoms and long
      disease-free intervals with initial survival of grafts and patients as in benign
      disease. The experience with multivisceral transplantation is still limited.

PMID- 15153444
TI  - Heterogeneous expression of neuroendocrine marker proteins in human
      undifferentiated carcinoma of the colon and rectum.
AB  - The expression of neuroendocrine marker proteins in undifferentiated colorectal
      cancers has not yet been studied in great detail. Therefore, the survival of 20
      patients with small cell undifferentiated colorectal cancers treated at our
      institution between 1982 and 1997 (0.8% of all operated colorectal carcinomas)
      was correlated with the extent of neuroendocrine differentiation. Chromogranin A,
      synaptophysin, syntaxin1, VAMP2, SNAP25, and alpha/beta-SNAP were used as
      neuroendocrine markers. Based on the degree of immunoreactivity for these marker
      proteins, tumors were divided into group 0 (<2% cells stained positive for
      neuroendocrine markers) and group 1 (>2% cells stained positive). Patients were
      followed up for at least 5 years or until death. Nine of twenty (45%)
      undifferentiated colorectal tumors expressed neuroendocrine markers (group 1).
      Only one patient of this group survived 2 years (11%), whereas the 2-year
      survival rate was 45.4% in group 0. Nine of eleven patients of group 0 were
      diagnosed in UICC stage I-III, whereas eight of nine tumors with expression of
      neuroendocrine markers were diagnosed in UICC stage IV (P = 0.002). Our results
      show that neuroendocrine differentiation is often seen in small cell
      undifferentiated colorectal cancer. It correlates with a more aggressive course
      of the disease.

PMID- 15153445
TI  - GOT1 xenografted to nude mice: a unique model for in vivo studies on SSTR
      mediated radiation therapy of carcinoid tumors.
AB  - Malignant carcinoid tumors express high numbers of somatostatin receptors.
      Radiation therapy using labeled somatostatin analogs is a novel treatment
      modality for these tumors. We have analyzed the biokinetics and therapeutic
      effect of radiolabeled somatostatin analog on a human midgut carcinoid grafted to
      nude mice. A transplantable human midgut carcinoid (GOT1) was grafted to the back
      of nude mice. Tumor-bearing mice were injected with (111)In-DTPA-D-Phe(1)
      octreotide, followed by measurement of (111)In activity concentration ratios in
      tumor tissues. Tumor-bearing mice were also injected with (177)Lu-DOTA-Tyr(3)
      octreotate and followed for 7 days. The concentration of (111)In-DTPA-D-Phe(1)
      octreotide in tumor tissues was very high 4 hours postinjection with 0.4-13% of
      injected activity per gram. Injection of 30-120 MBq (177)Lu-DOTA-Tyr(3)
      octreotate reduced tumor volume to 7-14% of the original tumor volume 7 days
      postinjection. Microscopic analysis of treated tumors revealed widespread areas
      of tumor cell necrosis and fibrosis. It was found that grafted GOT1 cells to nude
      mice represent an authentic model for studying human midgut carcinoids.
      Radiolabeled somatostatin analogs have a high selectivity for tumor tissue and
      can induce tumor cell necrosis. Radiotherapy of carcinoid tumors with (177)Lu
      DOTA-Tyr(3)-octreotate appears to be a promising treatment modality for either
      palliative treatment or completion therapy after attempted surgical cure.

PMID- 15153446
TI  - Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine
      tumors.
AB  - We have analyzed the expression of synaptic vesicle proteins in human
      neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis
      and treatment of neuroendocrine tumors. Biopsies from endocrine and nonendocrine
      tumors of the gastrointestinal tract, pancreas, and adrenals were examined by
      immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2),
      vesicular monoamine transporter 1 and 2 (VMAT1 and 2), and neuroendocrine
      secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the
      gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors
      (GISTs). None of the adenocarcinomas expressed SV2. VMAT1 and 2 were expressed in
      amine-producing tumors of the gastrointestinal tract (ECL cell and EC cell
      carcinoids) and in a small number of peptide-producing pancreatic endocrine
      tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as
      well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1 and
      2 for the uptake of 123I-MIBG in tumor cells was demonstrated. It was concluded
      that neuroendocrine tumors express multiple synaptic vesicle proteins that are
      useful in the histopathological diagnosis and classification of tumors. Vesicle
      proteins may prove to be useful for targeting tumor therapy.

PMID- 15153447
TI  - Implication of the INK4a/ARF locus in gastroenteropancreatic neuroendocrine
      tumorigenesis.
AB  - The INK4a/ARF locus on chromosome 9p21 is one of the important defenses against
      tumor development and engages both the Rb and the p53 tumor suppressor pathways
      through its capacity to encode two distinct proteins, p16(INK4a) and p14(ARF).
      Despite controversial reports, the body of present data suggests that tumor
      suppressors p16(INK4a) and p14(ARF) are targets of in-activation in GEP-NETs.
      Moreover, tumor type-specific aberrant p16(INK4a) silencing appears to be
      associated with advanced tumor stage and may function as a predictor of patients'
      outcome after surgical resection. Since conventional histological and biochemical
      assessment are limited with respect to predicting GEP-NET behavior or outcome,
      methylation profiles including INK4a/ARF might offer a tool to refine future
      diagnosis and therapeutic management of GEP-NET patients.

PMID- 15153448
TI  - Past, present, and future.

PMID- 15153449
TI  - Nurturing a culture of innovation.

PMID- 15153450
TI  - Genetics of human taste perception.
AB  - Genetic approaches are rapidly yielding new information about our sense of taste.
      This information comes from both molecular studies of genes encoding taste
      receptors and other taste-signaling components, and from studies of inherited
      variation in taste abilities. Our understanding of bitter taste has advanced by
      combined information from discovery and study of the TAS2R family of taste
      receptor genes, hand in hand with genetic linkage and positional cloning studies,
      notably on the ability to taste phenylthiocarbamide (PTC). Sweet and umami
      tastes, mediated by TAS1R receptors, are becoming well-characterized at the
      molecular genetic level, and these taste classes are now targets for linkage,
      positional cloning, and genetic association strategies. Salty and sour tastes are
      still poorly characterized in genetic terms, and represent opportunities for the
      future.

PMID- 15153451
TI  - Comparative study on adhesive performance of functional monomers.
AB  - Mild self-etch adhesives demineralize dentin only partially, leaving
      hydroxyapatite around collagen within a submicron hybrid layer. We hypothesized
      that this residual hydroxyapatite may serve as a receptor for chemical
      interaction with the functional monomer and, subsequently, contribute to adhesive
      performance in addition to micro-mechanical hybridization. We therefore
      chemically characterized the adhesive interaction of 3 functional monomers with
      synthetic hydroxyapatite, using x-ray photoelectron spectroscopy and atomic
      absorption spectrophotometry. We further characterized their interaction with
      dentin ultra-morphologically, using transmission electron microscopy. The monomer
      10-methacryloxydecyl dihydrogen phosphate (10-MDP) readily adhered to
      hydroxyapatite. This bond appeared very stable, as confirmed by the low
      dissolution rate of its calcium salt in water. The bonding potential of 4
      methacryloxyethyl trimellitic acid (4-MET) was substantially lower. The monomer 2
      methacryloxyethyl phenyl hydrogen phosphate (phenyl-P) and its bond to
      hydroxyapatite did not appear to be hydrolytically stable. Besides self-etching
      dentin, specific functional monomers have additional chemical bonding efficacy
      that is expected to contribute to their adhesive potential to tooth tissue.

PMID- 15153452
TI  - In vivo and in vitro permeability of one-step self-etch adhesives.
AB  - Adhesive dentistry should effectively restore the peripheral seal of dentin after
      enamel removal. We hypothesize that non-rinsing, simplified, one-step self-etch
      adhesives are effective for minimizing dentin permeability after tooth
      preparation procedures. Crown preparations in vital human teeth were sealed with
      Adper Prompt, Xeno III, iBond, or One-Up Bond F. Epoxy resin replicas were
      produced from polyvinyl siloxane impressions for SEM examination. Dentin surfaces
      from extracted human teeth were bonded with these adhesives and connected to a
      fluid-transport model for permeability measurements and TEM examination. Dentinal
      fluid droplets were observed from adhesive surfaces in resin replicas of in vivo
      specimens. In vitro fluid conductance of dentin bonded with one-step self-etch
      adhesives was either similar to or greater than that of smear-layer-covered
      dentin. TEM revealed water trees within the adhesives that facilitate water
      movement across the polymerized, highly permeable adhesives. Both in vitro and in
      vivo results did not support the proposed hypothesis.

PMID- 15153453
TI  - Characterization of apatite formed on alkaline-heat-treated Ti.
AB  - Alkaline-heat-treated titanium self-forms an apatite surface layer in vivo. The
      aim of the present study was to materialistically characterize the surface of
      alkaline-heat-treated titanium immersed in simulated body fluid (AHS-TI) and to
      examine the differentiation behavior of osteoblasts on AHS-TI. SEM, thin-film
      XRD, FTIR, and XPS analyses revealed that AHS-TI contained a 1.0- micro m-thick,
      low-crystalline, and [002] direction-oriented carbonate apatite surface. Human
      osteoblast-like SaOS-2 cells were cultured on polystyrene, titanium, and AHS-TI,
      and RT-PCR analyses of osteogenic differentiation-related mRNAs were conducted.
      On AHS-TI, the expression of bone sialoprotein mRNA was up-regulated as compared
      with that on polystyrene and titanium (p < 0.05). On AHS-TI, the expression of
      osteopontin and osteocalcin mRNAs was up-regulated as compared with that on
      polystyrene (p<0.05). The results indicate that the apatite was bone-like and
      accelerated the osteogenic differentiation of SaOS-2, suggesting that alkaline
      heat treatment might facilitate better integration of titanium implants with
      bone.

PMID- 15153455
TI  - Shear properties of the temporomandibular joint disc in relation to compressive
      and shear strain.
AB  - Shear stress can result in fatigue, damage, and irreversible deformation of the
      temporomandibular joint disc. Insight into the dynamic shear properties of the
      disc may give insight into the mechanism inducing tissue failure due to shear. We
      tested the hypothesis that the dynamic shear properties of the disc depend on the
      amount of shear and compressive strain. Twenty-four porcine discs were used for
      dynamic shear tests. The specimens were clamped between the plates of a loading
      apparatus under compressive strains of 5%, 10%, and 15%. Dynamic shear was
      applied to the specimen by a sinusoidal strain of, respectively, 0.5%, 1.0%, and
      1.5%. Both the dynamic elasticity and viscosity were proportional to compressive
      strain and inversely proportional to shear strain. These shear characteristics
      suggest a significant role of compressive and shear strain on the internal
      friction of the disc.

PMID- 15153454
TI  - Nanomechanical properties of facial sutures and sutural mineralization front.
AB  - The mechanical properties of craniofacial sutures have rarely been investigated.
      Three facial sutures-the pre-maxillomaxillary (PMS), the nasofrontal (NFS), and
      the zygomaticotemporal (ZTS)-and their corresponding sutural mineralization
      fronts in 8 young New Zealand White rabbits were subjected to nano-indentation
      with atomic force microscopy as a test of the hypothesis that they have different
      mechanical properties. The average elastic modulus of the PMS was 1.46 +/- 0.24
      MPa (mean +/- SD), significantly higher than both the ZTS (1.20 +/- 0.20) and NFS
      (1.16 +/- 0.18). The average elastic moduli of sutural mineralization fronts 30
      micro m away were significantly higher than their corresponding sutures and had
      the same distribution pattern: the PMS (2.07 +/- 0.24 MPa) significantly higher
      than both the ZTS (1.56 +/- 0.29) and NFS (1.71 +/- 0.22). Analysis of these data
      suggests that facial sutures and their immediately adjacent sutural
      mineralization fronts have different capacities for mechanical deformation. The
      elastic properties of sutures and sutural mineralization fronts are potentially
      useful for improving our understanding of their roles in development.

PMID- 15153456
TI  - Dynamic intra-articular space variation in clicking TMJs.
AB  - During mandibular movement, the geometric relationships of the articular surfaces
      in the temporomandibular joint (TMJ) change, so that the disc undergoes different
      stress concentrations with respect to time and position. In this study, we
      compared the intra-articular space variations of 13 clicking and 15 asymptomatic
      TMJs for jaw opening/closing. Magnetic resonance imaging and jaw tracking were
      combined to display the motion of the whole condyle within the fossa. In clicking
      TMJs, the mediolateral spread s of the stress-field trajectories was 2.4 +/- 1.0
      mm (s(max) = 4.9 +/- 2.1 mm) with an aspect ratio a/h of 2.5 +/- 1.6, both
      significantly greater than in controls (p < 0.05). The stress-field trajectories
      of the controls coincided during opening/closing (s = 0.9 +/- 0.2 mm, s(max) =
      1.8 +/- 0.8 mm, a/h = 1.6 +/- 0.3). Clicking TMJs showed much less coincident
      stress-field paths and much "flatter" stress-fields than controls during jaw
      opening/closing.

PMID- 15153457
TI  - The severity of periodontal disease is associated with the development of glucose
      intolerance in non-diabetics: the Hisayama study.
AB  - Inflammation is hypothesized to play a significant role in the development of
      type 2 diabetes; however, reports on clinical inflammatory conditions are
      limited. Studies have suggested that periodontitis affects glucose control in
      diabetics. This community-based study examined the relationship between
      periodontitis and glucose tolerance status, including changes in status. The
      relationship between periodontal condition and the results of a 75-g oral glucose
      tolerance test was examined in 961 adults in 1998. Deep pockets (mean pocket
      depth > 2.0 mm) were significantly associated with impaired glucose tolerance and
      with diabetes as compared with shallow pockets (< 1.3 mm). In the subgroup with
      normal glucose tolerance 10 years previously, subjects who subsequently developed
      impaired glucose tolerance were significantly more likely to have deep pockets.
      Deep pockets were closely related to current glucose tolerance status and the
      development of glucose intolerance.

PMID- 15153458
TI  - Dental pulp fibroblasts contain target cells for lysophosphatidic Acid.
AB  - Lysophosphatidic acid (LPA) is a locally produced bioactive phospholipid which is
      involved in tissue repair. The objective of this study was to determine whether
      dental pulp tissue also responds to the phospholipid. Effects of LPA on
      proliferation, differentiation, and mitogen-activated protein kinase (MAPK)
      signaling of dental pulp fibroblasts (DPF) were examined in vitro. We report that
      DPF express LPA receptors LPA1, LPA2, and LPA3 and respond to the ligand with
      increased mitogenic activity. Involvement of extracellular signal-regulated
      kinase, p38 MAPK, and c-Jun NH(2)-terminal kinase in LPA signaling could be
      demonstrated by use of specific inhibitors and detection of the phosphorylation
      status of the kinases. An increased mitogenic activity paralleled a decreased
      number of alkaline-phosphatase-positive cells and expression levels of dentin
      sialophosphoprotein and osteocalcin. Together, these results suggest that dental
      pulp fibroblasts can respond to LPA, a process that may play a role in pulp
      tissue repair.

PMID- 15153459
TI  - Dentonin, a fragment of MEPE, enhanced dental pulp stem cell proliferation.
AB  - Matrix extracellular phosphoglycoprotein (MEPE) is a SIBLING protein, found in
      bone and dental tissues. The purpose of this study was to determine whether a 23
      amino-acid peptide derived from MEPE (Dentonin or AC-100) could stimulate dental
      pulp stem cell (DPSC) proliferation and/or differentiation. DPSCs were isolated
      from erupted human molars, and the mitogenic potential of Dentonin in DPSCs was
      measured by BrdU immunoassay and cell-cycle gene SuperArray. Differentiation of
      DPSCs with Dentonin was characterized by Western blot and by osteogenesis gene
      SuperArray. Dentonin enhanced DPSC proliferation by down-regulating P16,
      accompanied by up-regulation of ubiquitin protein ligase E3A and human ubiquitin
      related protein SUMO-1. Enhanced cell proliferation required intact RGD and SGDG
      motifs in the peptide. This study shows that Dentonin can promote DPSC
      proliferation, with a potential role in pulp repair. Further studies are required
      to determine the usefulness of this material in vivo.

PMID- 15153460
TI  - Clonal persistence of oral Fusobacterium nucleatum in infancy.
AB  - Once established, early-colonizing bacterial species tend to persist in the
      mouth. To obtain detailed information on the population dynamics of early
      colonizing oral anaerobes, we examined the clonal diversity and persistence of
      clones among oral Fusobacterium nucleatum populations during the first 2 yrs of
      life. Consecutive salivary samples from 12 infants, collected at 2, 6, 12, 18,
      and 24 mos of age, yielded a total of 546 F. nucleatum isolates for clonal typing
      with arbitrarily primed PCR (AP-PCR). Up to 7 AP-PCR types were simultaneously
      detected in each sample. In 11 out of the 12 infants examined, AP-PCR types
      persisted for up to 1 yr. Strain turnover rate was high during the first year of
      life, but then the occurrence of persistent clones increased. This study
      indicates a wide genetic diversity within the species and provides evidence for
      the increasing persistence of F. nucleatum clones in the oral cavity with age.

PMID- 15153461
TI  - Salivary receptors for the proline-rich protein-binding and lectin-like adhesins
      of oral actinomyces and streptococci.
AB  - Colonization of the tooth surface by actinomyces and viridans group streptococci
      involves the attachment of these bacteria to adsorbed salivary components of the
      acquired enamel pellicle. The hypothesis that this attachment depends on specific
      adhesins has now been assessed from the binding of bacteria with well-defined
      adhesive properties to blots of SDS-PAGE-separated parotid and submandibular
      sublingual (SM-SL) saliva. Streptococcus sanguis and type 2 fimbriated
      Actinomyces naeslundii, which bound terminal sialic acid and Galbeta1-3GalNAc,
      respectively, recognized only a few SM-SL salivary components, primarily MG2. In
      contrast, type 1 fimbriated A. naeslundii and S. gordonii, which bound purified
      proline-rich proteins (PRPs), recognized several other components from both SM-SL
      and parotid saliva. Significantly, bacteria that lacked PRP-binding and the
      lectin-like activities detected by binding to MG2 failed to bind any immobilized
      salivary component. These findings suggest the involvement of specific adhesins
      in bacterial recognition of many adsorbed salivary proteins and glycoproteins.

PMID- 15153462
TI  - Advantages and disadvantages of cytidine deamination.
AB  - Cytidine deamination of nucleic acids underlies diversification of Ig genes and
      inhibition of retroviral infection, and thus, it would appear to be vital to host
      defense. The host defense properties of cytidine deamination require two distinct
      but homologous cytidine deaminases-activation-induced cytidine deaminase and
      apolipoprotein B-editing cytidine deaminase, subunit 3G. Although cytidine
      deamination has clear benefits, it might well have biological costs. Uncontrolled
      cytidine deamination might generate misfolded polypeptides, dominant-negative
      proteins, or mutations in tumor suppressor genes, and thus contribute to tumor
      formation. How cytidine deaminases target a given nucleic acid substrate at
      specific sequences is not understood, and what protects cells from uncontrolled
      mutagenesis is not known. In this paper, I shall review the functions and
      regulation of activation-induced cytidine deaminase and apolipoprotein B-editing
      cytidine deaminase, subunit 3G, and speculate about the basis for site
      specificity vis-a-vis generalized mutagenesis.

PMID- 15153463
TI  - Cutting edge: IL-2 is critically required for the in vitro activation of
      CD4+CD25+ T cell suppressor function.
AB  - CD4(+)CD25(+) T cells are potent immunoregulatory cells that suppress TCR-induced
      proliferation of CD4 and CD8 T cells in vitro by a cell contact-dependent
      mechanism. Addition of IL-2 or anti-CD28 abrogates CD4(+)CD25(+)-mediated
      suppression of proliferation and has been assumed to "break suppression." We
      examined IL-2 mRNA by quantitative PCR in cocultures of mouse CD4(+)CD25(+) and
      CD4(+)CD25(-) T cells. Although IL-2 gene transcription was inhibited in the
      presence or absence of exogenous IL-2, the addition of anti-CD28 stimulated
      endogenous IL-2 production. Surprisingly, transcription of IL-2 mRNA was also
      restored in the cocultures in the presence of anti-IL-2. These results are most
      compatible with a model in which CD4(+)CD25(+) T cells do not suppress the
      initial activation of CD4(+)CD25(-) T cells, but mediate their suppressive
      effects following production of IL-2 by the responder cells resulting in both the
      expansion of the CD4(+)CD25(+) T cells and the induction of their suppressor
      function.

PMID- 15153464
TI  - Cutting edge: NTB-A activates NK cells via homophilic interaction.
AB  - NK cells are an important component of the innate immune system. Their activity
      is tightly regulated by activating and inhibitory surface receptors. However, the
      exact functions of many activating surface receptors, as well as their ligands,
      still remain to be elucidated. NTB-A is a receptor on the surfaces of human NK,
      T, and B cells, mediating a signal whose malfunction may be involved in X-linked
      lymphoproliferative disease. However, the ligand of NTB-A has remained elusive so
      far. Using trimeric recombinant proteins, we now show that NTB-A is its own
      ligand. Homophilic interaction of NTB-A enhances NK cell cytotoxicity and
      influences NK cell proliferation and IFN-gamma secretion. We suggest that NTB-A
      is an interlymphocyte signaling molecule, which serves to orchestrate the
      activities of immune cells.

PMID- 15153465
TI  - Cutting edge: hemokinin has substance P-like function and expression in
      inflammation.
AB  - Substance P (SP) belongs to the tachykinin family of molecules. SP, cleaved from
      preprotachykinin A, is a neuropeptide and a proinflammatory leukocyte product. SP
      engages neurokinin 1 receptor (NK-1R) to stimulate cells. Hemokinin (HK) is
      another tachykinin that binds NK-1R. HK comes from preprotachykinin C, which is
      distinct from preprotachykinin A. We determined whether HK functions like SP at
      inflammatory sites. Preprotachykinin C mRNA was in murine schistosome granulomas
      and intestinal lamina propria mononuclear cells. Granuloma T cells and
      macrophages expressed preprotachykinin C mRNA. HK bound granuloma T cell NK-1R
      with high affinity. SP and HK stimulated IFN-gamma production with equal potency.
      NK-1R antagonist blocked the effect of SP and HK on IFN-gamma secretion. Thus,
      both HK and SP are expressed at sites of chronic inflammation and share cell
      origin, receptor, and immunoregulatory function. Two distinct but functionally
      overlapping tachykinins govern inflammation through NK-1R at sites of chronic
      inflammation.

PMID- 15153466
TI  - Cutting edge: effector memory CD8+ T cells play a prominent role in recall
      responses to secondary viral infection in the lung.
AB  - The relative contributions of CD62L(high) (central) memory and CD62L(low)
      (effector) memory T cell populations to recall responses are poorly understood,
      especially in the respiratory tract. In this study, we took advantage of a dual
      adoptive transfer system in the mouse to simultaneously follow the recall
      response of effector and central memory subpopulations to intranasal
      parainfluenza virus infection. Using MHC class I and class II multimers, we
      tracked the responses of Ag-specific CD8(+) and CD4(+) memory T cells in the same
      animals. The data show that effector memory T cells mounted recall responses that
      were equal to, or greater than, those mounted by central memory T cells.
      Moreover, effector memory T cells were more efficient at subsequently
      establishing a second generation of memory T cells. These data contrast with
      other studies indicating that central memory CD8(+) T cells are the prominent
      contributors to systemic virus infections.

PMID- 15153467
TI  - Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in
      vivo inhibition of effector cell proliferation.
AB  - Regulatory T cells preserve tolerance to peripheral self-Ags and may control the
      response to allogeneic tissues to promote transplantation tolerance. Although
      prior studies have demonstrated prolonged allograft survival in the presence of
      regulatory T cells (T-reg), data documenting the capacity of these cells to
      promote tolerance in immunocompetent transplant models are lacking, and the
      mechanism of suppression in vivo remains unclear. We used a TCR transgenic model
      of allograft rejection to characterize the in vivo activity of CD4(+)CD25(+) T
      reg. We demonstrate that graft Ag-specific T-reg effectively intercede in the
      rejection response of naive T cells to established skin allografts. Furthermore,
      CFSE labeling demonstrates impaired proliferation of naive graft Ag-specific T
      cells in the draining lymph node in the presence of T-reg. These results confirm
      the efficacy of T-reg in promoting graft survival and suggest that their
      suppressive action is accomplished in part through inhibition of proliferation.

PMID- 15153468
TI  - Small interfering RNAs mediate sequence-independent gene suppression and induce
      immune activation by signaling through toll-like receptor 3.
AB  - Small interfering (si) and short hairpin (sh) RNAs induce robust degradation of
      homologous mRNAs, making them a potent tool to achieve gene silencing in
      mammalian cells. Silencing by siRNAs is used widely because it is considered
      highly specific for the targeted gene, although a recent report suggests that
      siRNA also induce signaling through the type I IFN system. When human embryonic
      kidney 293 (HEK293) or keratinocyte (HaCaT) cell lines or human primary dendritic
      cells or macrophages were transfected with siRNA or shRNAs, suppression of
      nontargeted mRNA expression was detected. Additionally, siRNA and shRNA,
      independent of their sequences, initiated immune activation, including IFN-alpha
      and TNF-alpha production and increased HLA-DR expression, in transfected
      macrophages and dendritic cells. The siRNAs induced low, but significant, levels
      of IFN-beta in HEK293 and HaCaT cells. Secretion of these cytokines increased
      tremendously when HEK293 cells overexpressed Toll-like receptor 3 (TLR3), and the
      increased secretion of IFN-beta was inhibited by coexpression of an inhibitor of
      TIR domain-containing adapter-inducing IFN-beta, the TLR3 adaptor protein linked
      to IFN regulatory factor 3 signaling. Although siRNA and shRNA knockdown of genes
      represents a new and powerful tool, it is not without nonspecific effects, which
      we demonstrate are mediated in part by signaling through TLR3.

PMID- 15153469
TI  - Essential role of bystander cytotoxic CD122+CD8+ T cells for the antitumor
      immunity induced in the liver of mice by alpha-galactosylceramide.
AB  - We recently reported that NK cells and CD8(+) T cells contribute to the
      antimetastatic effect in the liver induced by alpha-galactosylceramide (alpha
      GalCer). In the present study, we further investigated how CD8(+) T cells
      contribute to the antimetastatic effect induced by alpha-GalCer. The injection of
      anti-CD8 Ab into mice 3 days before alpha-GalCer injection (2 days before
      intrasplenic injection of B16 tumors) did not inhibit IFN-gamma production nor
      did it reduce the NK activity of liver mononuclear cells after alpha-GalCer
      stimulation. However, it did cause a reduction in the proliferation of liver
      mononuclear cells and mouse survival time. Furthermore, although the depletion of
      NK and NKT cells (by anti-NK1.1 Ab) 2 days after alpha-GalCer injection no longer
      decreased the survival rate of B16 tumor-injected mice, the depletion of CD8(+) T
      cells did. CD122(+)CD8(+) T cells in the liver increased after alpha-GalCer
      injection, and antitumor cytotoxicity of CD8(+) T cells in the liver gradually
      increased until day 6. These CD8(+) T cells exhibited an antitumor cytotoxicity
      toward not only B16 cells, but also EL-4 cells, and their cytotoxicity
      significantly decreased by the depletion of CD122(+)CD8(+) T cells. The critical,
      but bystander role of CD122(+)CD8(+) T cells was further confirmed by adoptive
      transfer experiments into CD8(+) T cell-depleted mice. Furthermore, it took 14
      days after the first intrasplenic B16/alpha-GalCer injection for the mice to
      generate CD8(+) T cells that can reject s.c. rechallenged B16 cells. These
      findings suggest that alpha-GalCer activates bystander antitumor CD122(+)CD8(+) T
      cells following NK cells and further induces an adaptive antitumor immunity due
      to tumor-specific memory CD8(+) CTLs.

PMID- 15153470
TI  - A spontaneously arising pancreatic tumor does not promote the differentiation of
      naive CD8+ T lymphocytes into effector CTL.
AB  - In this report, we address whether a growing tumor provides sufficient
      inflammatory signals to promote activation, clonal expansion, and acquisition of
      effector functions by naive tumor-specific CD8(+) T lymphocytes. CD8(+) T
      lymphocytes obtained from hemagglutinin (HA)-specific clone 4 TCR-transgenic mice
      were injected into recipient mice that spontaneously develop pancreatic tumors
      expressing HA as a tumor-associated Ag (RIP-Tag2-HA mice). When 3 x 10(6) clone 4
      CD8(+) T cells were transferred into tumor-bearing mice, the cells became
      activated in the pancreatic lymph nodes where they proliferated and acquired
      effector functions such as cytolytic activity and IFN-gamma production.
      Surprisingly, reducing the number of adoptively transferred CD8(+) T cells led to
      a parallel reduction in the proportion of the activated cells that exhibited
      effector functions, suggesting that CTL differentiation was induced by the large
      numbers of activated CD8(+) T cells and not the tumor environment. Provision of
      tumor-specific CD4(+) helper cells provided the signals required to promote both
      the development of CTL effector functions and increased clonal expansion,
      resulting in tumor eradication. Considering that only small numbers of tumor
      specific CD8(+) T cells would be present in a conventional T cell repertoire,
      these data suggest that tumor growth alone may not provide the inflammatory
      signals necessary to support the development of CD8(+) T cell effector functions.

PMID- 15153471
TI  - Tolerance to DNA in (NZB x NZW)F1 mice that inherit an anti-DNA V(H) as a
      conventional micro H chain transgene but not as a V(H) knock-in transgene.
AB  - Lupus-prone (NZB x NZW)F(1) (BWF(1)) mice were made transgenic (Tg) for an anti
      DNA Ab inherited either as a conventional V(H)3H9- micro H chain Tg (3H9- micro )
      with or without a conventional V(kappa)8-kappa Tg, or a V(H)3H9 V(H) knock-in Tg
      allele (3H9R) with or without a V(kappa)4 V(kappa) knock-in Tg allele
      (V(kappa)4R). V(H)3H9 yields an anti-DNA Ab with most L chains including an anti
      ssDNA with the V(kappa)8 Tg and an anti-dsDNA with the V(kappa)4 Tg. BWF(1) mice
      that inherited the conventional 3H9- micro had normal serum IgM, little to none
      of which was encoded by 3H9- micro, and only a small percentage of those mice had
      serum anti-DNA, none of which was transgene encoded. B cells expressing the
      conventional 3H9- micro Tg were anergic. BWF(1) mice that inherited the knock-in
      3H9R Tg allele also had normal serum IgM, one-half of which was encoded by 3H9R,
      and produced anti-DNA encoded by the Tg allele. Most B cells expressing the knock
      in 3H9R Tg also had an anergic phenotype. The results indicate that autoimmune
      prone BWF(1) mice initially develop effective B cell tolerance to DNA through
      anergy, and anergy was sustained in 3H9- micro Tg peripheral B cells but not in
      3H9R Tg B cells. B cells expressing the 3H9R knock-in Tg allele were able to
      achieve an activation threshold that B cells expressing the 3H9- micro
      conventional Tg could not. The maintenance of B cell tolerance to DNA in
      autoimmune-prone BWF(1) mice appears to differ from both normal mice and
      autoimmune-prone MRL(lpr/lpr) mice.

PMID- 15153472
TI  - Mechanisms of Vdelta1 gammadelta T cell activation by microbial components.
AB  - There are two major subsets of gammadelta T cell in humans. Vgamma2Vdelta2 T
      cells predominate in the circulation and significantly expand in vivo during a
      variety of infectious diseases. Ags identified for the Vdelta2 T cells are
      nonpeptide phosphate, amine, and aminobisphosphonate compounds. In contrast,
      Vdelta1-encoded TCRs account for the vast majority of gammadelta T cells in
      tissues such as intestine and spleen. Some of these T cells recognize CD1c and
      MHC class I-related chain (MICA/B) molecules [correction]. These T cells are
      cytotoxic and use both perforin- and Fas-mediated cytotoxicity. A fundamental
      question is how these gammadelta T cells are activated during microbial exposure
      to carry out effector functions. In this study, we provide evidence for a
      mechanism by which Vdelta1 gammadelta T cells are activated by inflammatory
      cytokines in the context of the Vdelta1 TCR. Dendritic cells are necessary as
      accessory cells for microbial Ag-mediated Vdelta1 gammadelta T cell activation.
      Cytokine (IL-12), adhesion (LFA3/CD2, LFA1/ICAM1) and costimulatory (MHC class I
      related chain (MICA/B) molecules/NK-activating receptor G2D) molecules play a
      significant role along with Vdelta1 TCR in this activation.

PMID- 15153473
TI  - The antigen-presenting activity of fresh, adult parenchymal microglia and
      perivascular cells from retina.
AB  - Although several observations show local T cell recognition of retinal Ag, there
      has been no direct demonstration that the APC were retinal derived, rather than
      recruited. In this study, CD45(+) cells isolated from immunologically quiescent
      murine retina were tested in vitro for functional evidence of Ag presentation to
      naive and Ag-experienced CD4 T cells specific for beta-galactosidase. Because
      CD45(+) cells from brain have been reported to be efficient APC, they were
      included for comparison. Measures of activation included changes in CD4, CD25,
      CD44, CD45RB, CD62L, CD69, caspase-3 activation, CFSE dilution, size, number of
      cells recovered, and cytokine production. Retinal CD45(+) cells gave no evidence
      of Ag-dependent TCR ligation in naive T cells, unlike splenic APC and CD45(+)
      cells from brain, which supported potent responses. Instead, addition of retinal
      CD45(+) cells to cocultures of naive 3E9 T cells plus splenic APC reduced the
      yield of activated T cells and cytokine production by limiting T cell activation
      at early time points. Ag-experienced T cells responded weakly to Ag presented by
      retinal CD45(+) cells. Activating the retinal cells with IFN-gamma, anti-CD40, or
      LPS incrementally increased their APC activity. Addition of neutralizing Abs to
      TGF-beta did not reveal suppressed retinal APC activity. Because retina lacks
      tissue equivalents of meninges and choroid plexus, rich sources of dendritic
      cells in brain, cells from retina may better represent the APC activity of fresh,
      adult CNS parenchymal and perivascular cells. The activity of the retinal CD45(+)
      cells appears to be directed to limiting T cell responses.

PMID- 15153474
TI  - Activation-induced cell death limits effector function of CD4 tumor-specific T
      cells.
AB  - A number of studies have documented a critical role for tumor-specific CD4(+)
      cells in the augmentation of immunotherapeutic effector mechanisms. However, in
      the context of an extensive tumor burden, chronic stimulation of such CD4(+) T
      cells often leads to the up-regulation of both Fas and Fas ligand, and
      coexpression of these molecules can potentially result in activation-induced cell
      death and the subsequent loss of effector activity. To evaluate the importance of
      T cell persistence in an experimental model of immunotherapy, we used DO11 Th1
      cells from wild-type, Fas-deficient, and Fas ligand-deficient mice as effector
      populations specific for a model tumor Ag consisting of an OVA-derived
      transmembrane fusion protein. We found that the prolonged survival of Fas
      deficient DO11 Th1 cells led to a more sustained tumor-specific response both in
      vitro and in vivo. Importantly, both Fas- and Fas ligand-deficient Th1 cells
      delayed tumor growth and cause regression of established tumors more effectively
      than wild-type Th1 cells, indicating that resistance to activation-induced cell
      death significantly enhances T cell effector activity.

PMID- 15153475
TI  - Differential requirements for endosomal reduction in the presentation of two H2
      E(d)-restricted epitopes from influenza hemagglutinin.
AB  - We examined the role of reduction in the presentation of two H2-E(d)-restricted
      epitopes (site 1 epitope (S1) and site 3 epitope (S3)) occupying distinct domains
      of the influenza hemagglutinin major subunit that contains four intrachain
      disulfide bonds and is connected to the virion by one interchain bond. S3 is
      situated within the stalk region that unfolds in response to mild acidification,
      and loads onto recycling H2-E(d) in the early endosome, while S1, located in the
      structurally constrained globular domain, loads onto nascent H2-E(d) in the late
      endosome. Predicting dependence upon reduction for either epitope seemed
      plausible but the results from several approaches were clear: presentation of S1
      but not S3 is reduction dependent. Surprisingly, IFN-gamma-inducible lysosomal
      thiol reductase (GILT), the only reductase thus far known to be involved in MHC
      class II-restricted processing, is not necessary for the generation of S1.
      However, GILT is necessary for presentation of either epitope when the virus is
      pretreated with a reducible cross-linker. The results suggest that unfolding of
      the Ag, perhaps a prerequisite for proteolytic processing in many cases, proceeds
      either spontaneously in the early endosome or via reduction in a later endosome.
      They further imply mechanisms for GILT-independent reduction in the late
      endosome, with GILT perhaps being reserved for more intractable Ags.

PMID- 15153476
TI  - Enhanced T cell proliferation in mice lacking the p85beta subunit of
      phosphoinositide 3-kinase.
AB  - Phosphoinositide 3-kinase activation is important for lymphocyte proliferation
      and survival. Disrupting the gene that encodes the major phosphoinositide 3
      kinase regulatory isoform p85alpha impairs B cell development and proliferation.
      However, T cell functions are intact in the absence of p85alpha. In this study,
      we test the hypothesis that the related isoform p85beta is an essential
      regulatory subunit for T cell signaling. Unexpectedly, T cells lacking p85beta
      showed a marked increase in proliferation and decreased death when stimulated
      with anti-CD3 plus IL-2. Both CD4(+) and CD8(+) T cells completed more cell
      divisions. Transcriptional profiling revealed reduced levels of caspase-6 mRNA in
      p85beta-deficient T cells, which was paralleled by reduced caspase-6 enzyme
      activity. Increased T cell accumulation was also observed in vivo following
      infection of p85beta-deficient mice with mouse hepatitis virus. Together, these
      results suggest a unique role for p85beta in limiting T cell expansion.

PMID- 15153477
TI  - Requirement for donor and recipient CD40 expression in cardiac allograft
      rejection: induction of Th1 responses and influence of donor-derived dendritic
      cells.
AB  - Costimulation through the CD40-CD40 ligand (CD40L) pathway is critical to
      allograft rejection, in that anti-CD40L mAb therapy prolongs allograft survival.
      However, the majority of studies exploring CD40-CD40L interactions have targeted
      CD40L. Less is known about the requirement for donor- and/or host-derived CD40
      during rejection. This study assessed the relative contributions of donor and
      recipient CD40 expression to the rejection process. As the effectiveness of
      costimulatory blockade may be mouse strain dependent, this study explored the
      requirement for donor and recipient CD40 expression in BALB/c and C57BL/6 mice.
      Wild-type (WT) and CD40(-/-) BALB/c recipients readily rejected WT and CD40(-/-)
      C57BL/6 allografts, and rejection was associated with a prominent Th1 response.
      In contrast, CD40(-/-) C57BL/6 recipients failed to reject WT or CD40(-/-) BALB/c
      allografts and did not mount Th1 or Th2 responses. However, injection of donor
      CD40(-/-) dendritic cells induced both Th1 and Th2 responses and allograft
      rejection in CD40(-/-) C57BL/6 recipients. Finally, WT C57BL/6 mice rejected
      CD40(-/-) allografts, but this rejection response was associated with muted Th1
      responses. These findings demonstrate that 1) CD40 expression by the recipient or
      the graft may impact on the immune response following transplantation; 2) the
      requirement for CD40 is influenced by the mouse strain; and 3) the requirement
      for CD40 in rejection may be bypassed by donor DC. Further, as CD40 is not
      required for rejection in BALB/c recipients, but anti-CD40L mAb prolongs graft
      survival in these mice, these results suggest that anti-CD40L therapy functions
      at a level beyond disruption of CD40-CD40L interactions.

PMID- 15153478
TI  - The novel murine CD4+CD8+ thymocyte cell line exhibits lineage commitment into
      both CD4+ and CD8+ T cells by altering the intensity and the duration of anti-CD3
      stimulation in vitro.
AB  - A CD4(+)CD8(+) double-positive thymocyte cell line, 257-20-109 was established
      from BALB/c mice thymocytes and used to analyze the requirements to induce CD4 or
      CD8 single-positive (SP) T cells. CD4SP cells were induced from 257-20-109 cells
      by anti-CD3 stimulation in the presence of the FcR-positive macrophage cell line,
      P388D1. During stimulation, maturation events, such as the down-regulation of
      CD24 and the up-regulation of CD69, H-2D(d), CD5, and Bcl-2, were recognized.
      Furthermore, these CD4SP cells appeared to be functional because the cells
      produced IL-2 and IL-4 when activated with phorbol ester and calcium ionophore.
      In contrast, CD8SP cells could be induced by stimulation with fixed anti-CD3
      after removal of stimulation. To investigate the extent of signals required for
      CD4SP and CD8SP, the cells stimulated under either condition for 2 days were
      sorted and transferred to different culture conditions. These results suggested
      that the fate of lineage commitment was determined within 2 days, and that CD4
      lineage commitment required longer activation. Furthermore, the experiments with
      subclones of 257-20-109 demonstrated that the lower density of CD3 did not shift
      the cells from CD4SP to CD8SP, but only reduced the amount of CD4SP cells. In
      contrast, when the 257-20-109 cells were stimulated by the combination of fixed
      anti-CD3 and anti-CD28, the majority of the cells shifted to CD4SP, with an
      enhancement of extracellular signal-regulated kinase 1 phosphorylation. Our
      results indicate that the signals via TCR/CD3 alone shifted the double-positive
      cells to CD8SP cells, but the reinforced signals via TCR/CD3 and costimulator
      could commit the cells to CD4SP.

PMID- 15153479
TI  - A novel approach to specific allergy treatment: the recombinant fusion protein of
      a bacterial cell surface (S-layer) protein and the major birch pollen allergen
      Bet v 1 (rSbsC-Bet v 1) combines reduced allergenicity with immunomodulating
      capacity.
AB  - Counterregulating the disease-eliciting Th2-like immune response of allergen
      specific Th lymphocytes by fostering an allergen-specific Th1-like response is a
      promising concept for future immunotherapy of type I allergy. The use of
      recombinant allergens combined with more functional adjuvants has been proposed.
      In this respect, we present a novel approach. The gene sequence encoding the
      major birch pollen allergen, Bet v 1, was fused with the gene encoding the
      bacterial cell surface (S-layer) protein of Geobacillus stearothermophilus,
      resulting in the recombinant protein, rSbsC-Bet v 1. rSbsC-Bet v 1 contained all
      relevant Bet v 1-specific B and T cell epitopes, but was significantly less
      efficient to release histamine than rBet v 1. In cells of birch pollen-allergic
      individuals, rSbsC-Bet v 1 induced IFN-gamma along with IL-10, but no Th2-like
      response, as observed after stimulation with Bet v 1. Intracellular cytokine
      staining revealed that rSbsC-Bet v 1 promoted IFN-gamma-producing Th cells.
      Moreover, rSbsC-Bet v 1 induced IFN-gamma synthesis in Bet v 1-specific Th2 cell
      clones, and importantly, increased IL-10 production in these cells. In
      conclusion, genetic fusion of an allergen to S-layer proteins combined reduced
      allergenicity with immunomodulatory capacity. The strategy described in this work
      may be generally applied to design vaccines for specific immunotherapy of type I
      allergy with improved efficacy and safety.

PMID- 15153481
TI  - Elimination of an immunodominant CD4+ T cell epitope in human IFN-beta does not
      result in an in vivo response directed at the subdominant epitope.
AB  - The BALB/cByJ mouse strain displays an immunodominant T cell response directed at
      the same CD4(+) T cell epitope peptide region in human IFN-beta, as detected in a
      human population-based assay. BALB/cByJ mice also recognize a second region of
      the protein with a lesser magnitude proliferative response. Critical residue
      testing of the immunodominant peptide showed that both BALB/cByJ mice and the
      human population response were dependent on an isoleucine residue at position
      129. A variant IFN-beta molecule was constructed containing the single amino acid
      modification, I129V, in the immunodominant epitope. The variant displayed 100% of
      control antiproliferation activity. Mice immunized with unmodified IFN-beta
      responded weakly in vitro to the I129V variant. However, BALB/cByJ mice immunized
      with the I129V variant were unable to respond to either the I129V variant or the
      unmodified IFN-beta molecule by either T cell proliferation or Ag-specific IgG1
      Ab production. This demonstrates that a single amino acid change in an
      immunodominant epitope can eliminate an immune response to an otherwise intact
      therapeutic protein. The elimination of the immunodominant epitope response also
      eliminated the response to the subdominant epitope in the protein. Modifying
      functionally immunodominant T cell epitopes within proteins may obviate the need
      for additional subdominant epitope modifications.

PMID- 15153480
TI  - Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in
      HLA class I and class II molecules.
AB  - An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th
      cells and CD8(+) CTLs. A promising tool in cancer immunotherapy is, therefore,
      the genetic modification of dendritic cells (DCs) by introducing the coding
      region of a tumor Ag, of which the antigenic peptides will be presented in both
      HLA class I and class II molecules. This can be achieved by linking the tumor Ag
      to the HLA class II-targeting sequence of an endosomal or lysosomal protein. In
      this study we compared the efficiency of the targeting signals of invariant
      chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP. Human DCs were
      electroporated before or after maturation with mRNA encoding unmodified enhanced
      green fluorescent protein (eGFP) or eGFP linked to various targeting signals. The
      lysosomal degradation inhibitor chloroquine was added, and eGFP expression was
      evaluated at different time points after electroporation. DCs were also
      electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting
      signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA
      class I and class II molecules was investigated. Our data suggest that proteins
      linked to the different targeting signals are targeted to the lysosomes and are
      indeed presented in the context of HLA class I and class II molecules, but with
      different efficiencies. Proteins linked to the LAMP1 or DC-LAMP signal are more
      efficiently presented than proteins linked to the invariant chain-targeting
      signal. Furthermore, DCs electroporated after maturation are more efficient in Ag
      presentation than DCs electroporated before maturation.

PMID- 15153482
TI  - Duration of alloantigen presentation and avidity of T cell antigen recognition
      correlate with immunodominance of CTL response to minor histocompatibility
      antigens.
AB  - CD8 T lymphocytes (CTL) responsive to immunodominant minor histocompatibility
      (minor H) Ags are thought to play a disproportionate role in allograft rejection
      in MHC-identical solid and bone marrow transplant settings. Although many studies
      have addressed the mechanisms underlying immunodominance in models of infectious
      diseases, cancer immunotherapy, and allograft immunity, key issues regarding the
      molecular basis of immunodominance remain poorly understood. In this study, we
      exploit the minor H Ag system to understand the relationship of the various
      biochemical parameters of Ag presentation and recognition to immunodominance. We
      show that the duration of individual minor H Ag presentation and the avidity of T
      cell Ag recognition influence the magnitude and, hence, the immunodominance of
      the CTL response to minor H Ags. These properties of CTL Ag presentation and
      recognition that contribute to immunodominance have implications not only for
      tissue transplantation, but also for autoimmunity and tumor vaccine design.

PMID- 15153483
TI  - Extensive replicative capacity of human central memory T cells.
AB  - To characterize the replicative capacity of human central memory (T(CM)) CD4 T
      cells, we have developed a defined culture system optimized for the ex vivo
      expansion of Ag-specific CD4(+) T cells. Artificial APCs (aAPCs) consisting of
      magnetic beads coated with Abs to HLA class II and a costimulatory Ab to CD28
      were prepared; peptide-charged HLA class II tetramers were then loaded on the
      beads to provide Ag specificity. Influenza-specific DR*0401 CD4 T(CM) were
      isolated from the peripheral blood of normal donors by flow cytometry. Peptide
      loaded aAPC were not sufficient to induce resting CD4 T(CM) to proliferate. In
      contrast, we found that the beads efficiently promoted the growth of previously
      activated CD4 T(CM) cells, yielding cultures with >80% Ag-specific CD4 cells
      after two stimulations. Further stimulation with peptide-loaded aAPC increased
      purity to >99% Ag-specific T cells. After in vitro culture for 3-12 wk, the flu
      specific CD4 T(CM) had surface markers that were generally consistent with an
      effector phenotype described for CD8 T cells, except for the maintenance of CD28
      expression. The T(CM) were capable of 20-40 mean population doublings in vitro,
      and the expanded cells produced IFN-gamma, IL-2, and TNF-alpha in response to Ag,
      and a subset of cells also secreted IL-4 with PMA/ionomycin treatment. In
      conclusion, aAPCs expand T(CM) that have extensive replicative capacity, and have
      potential applications in adoptive immunotherapy as well as for studying the
      biology of human MHC class II-restricted T cells.

PMID- 15153484
TI  - Fatal acute lymphoblastic leukemia in mice transgenic for B cell-restricted bcl
      xL and c-myc.
AB  - Expression of the c-myc gene is frequently dysregulated in malignant tumors and
      translocations of c-myc into the Ig H chain locus are associated with Burkitt's
      type lymphoma. There is indirect evidence that bcl-x, an anti-apoptotic member of
      the bcl-2 gene family, may also contribute to a variety of B lymphoid tumors. In
      this study, we show that mice transgenic for both B cell-restricted c-myc and bcl
      x(L) developed aggressive, acute leukemias expressing early B lineage and stem
      cell surface markers. Of interest, the tumor cells proliferated and
      differentiated down the B cell developmental pathway following in vitro treatment
      with IL-7. Analysis of sorted leukemic cells from spleen indicated constitutive
      expression of sterile micro and kappa transcripts in combination with evidence
      for D-J(H) DNA rearrangements. Several B cell-specific genes were either not
      expressed or were expressed at low levels in primary tumor cells and were induced
      following culture with IL-7. IL-7 also increased V-Jkappa and V-DJ(H)
      rearrangements. These data demonstrate oncogenic synergy between c-myc and bcl
      x(L) in a new mouse model for acute lymphoblastic leukemia. Tumors in these
      animals target an early stage in B cell development characterized by the
      expression of both B lineage and stem cell genes.

PMID- 15153485
TI  - Nucleosomes are exposed at the cell surface in apoptosis.
AB  - Apoptotic cells are considered the source of DNA, histones, and nucleoprotein
      complexes that drive the production of autoantibodies in systemic lupus
      erythematosus. However, the role of apoptotic cells in the activation of the
      immune system is not clear. To explore interactions that may initiate or sustain
      the production of anti-nuclear autoantibodies, we characterized the binding of a
      large panel of monoclonal autoantibodies to apoptotic cells. Autoantibodies to
      DNA, individual core histones, histone-DNA complexes, or the native nucleosome
      core particle revealed a consistent and specific binding pattern in confocal
      microscopy. Immunoreactive epitopes were detected in the cytoplasm and
      accumulated along the surface of the fragmenting nucleus in a caspase-dependent
      manner. Ag-Ab complexes on nuclear fragments that had emerged from the plasma
      membrane were accessible to anti-isotype-reactive microparticles. Moreover,
      autoantibodies specific for the nucleosome core or its molecular components
      selectively precipitated a complex of core histones and DNA from the cytosol at 4
      h after induction of apoptosis. These observations identify distinct steps in the
      release of nucleosomes from the nucleus and their exposure at the cell surface.
      Furthermore, the results indicate a direct role for nucleosomes in the execution
      of apoptosis, clearance of apoptotic cells, and regulation of anti-nuclear
      autoantibody production.

PMID- 15153486
TI  - APCs in the anterior uveal tract do not migrate to draining lymph nodes.
AB  - The migration of APCs from sites of infection and their maturation are critical
      elements in the generation of immune responses. However, the paths by which
      intraocular Ags migrate to draining lymph nodes are not known because the eye has
      limited lymphatic vessels. To date, only dendritic cells from the cornea and
      conjunctiva have been shown to emigrate. We demonstrate that phagocytic APCs in
      the anterior uveal tissues of the murine eye that ingest fluorescent latex beads
      do not migrate to regional lymph nodes. The beads are ingested in the uveal tract
      by cells expressing MHC class II, CD11c, or F4/80. Using intravital time-lapse
      videomicroscopy to monitor iris APC migration after anterior chamber injection of
      fluorescent Ag, fluorescently labeled APCs fail to move at multiple observation
      times, even in the presence of Ag and LPS. Whereas an as yet unidentified ocular
      nonphagocytic APC subset might migrate from the anterior uveal tissues, it is
      more probable that immune responses in the draining lymph nodes are engendered by
      soluble Ag escaping the eye through interstitial spaces. The inability of
      anterior uveal tissue APCs to migrate to lymph nodes may contribute to deviant
      immune responses that dominate after Ags are introduced into the anterior
      chamber.

PMID- 15153487
TI  - Recruitment of transferrin receptor to immunological synapse in response to TCR
      engagement.
AB  - T cell receptor engagement by an APC induces the formation of a highly organized
      complex of surface receptors and intracellular signaling molecules, known as the
      immunological synapse, at the site of cell-cell contact. The transferrin receptor
      (TfR, CD71) is normally present in the plasma membrane and recycling endosomes.
      In this study, we show that, although the TfR is typically absent from lipid
      rafts at steady state, stimulation with a mitogenic mixture of anti-CD3 Abs of
      human Jurkat T cells leads to a rapid compartmentalization of the TfR into lipid
      rafts accompanying that of CD3epsilon and activated Lck. This change occurs very
      rapidly and is accompanied by an increase in the surface expression of the TfR,
      probably by translocation from an internal endosomal pool. TfR recruitment to
      lipid rafts was also observed in primary T cells treated with mitogenic anti-CD3
      Abs and in Jurkat T cell-APC conjugates. The use of beads coated with Abs
      indicates that the surface and endosomal TfR pools redistribute to the contact
      site region in response to engagement of CD28 and CD3. In T cell-APC conjugates,
      the T cell TfR endosomal pool relocates beneath the contact site, whereas surface
      TfR localizes to the peripheral ring of the immunological synapse. In the
      presence of specific anti-TfR Abs, the total number of T cell-APC contacts and
      the percentage of conjugates with CD3 and Lck translocated to the contact site
      were reduced. Our results therefore suggest the involvement of the TfR in the
      formation of the immunological synapse.

PMID- 15153488
TI  - Unusual chemokine receptor antagonism involving a mitogen-activated protein
      kinase pathway.
AB  - Antagonism of chemokines on chemokine receptors constitutes a new regulatory
      principle in inflammation. Eotaxin (CCL11), an agonist for CCR3 and an attractant
      of eosinophils, basophils, and Th2 lymphocytes, was shown to act as an antagonist
      for CCR2, which is widely expressed on leukocytes and is essential for
      inflammatory responses. In this report we provide direct evidence for a novel
      mechanism how chemokine receptor function can be arrested by endogenous ligands.
      We show that binding of eotaxin to CCR2 stimulates the mitogen-activated protein
      kinases extracellular signal-regulated kinase 1/2 (ERK1/2). Activation of the
      mitogen-activated protein kinase kinase 1/2-ERK pathway is indispensable for
      eotaxin-mediated attenuation of CCR2 function, as inhibition of ERK
      phosphorylation abolishes the arresting effect. ERK is also activated by CCR2
      agonists, e.g., monocyte chemoattractant protein-1 (CCL2). However, the involved
      pathways are different, although in either case coupling of CCR2 to pertussis
      toxin-sensitive heterotrimeric G proteins is necessary. The results are in
      agreement with the view that CCR2 could assume different activation states
      depending on the ligand it encounters. With respect to actin polymerization and
      calcium mobilization, the different activation states lead to agonistic and
      antagonistic responses. It is conceivable that the intracellular signal
      transduction pathway that is activated by eotaxin could cause an attenuation of
      proinflammatory responses mediated by CCR2.

PMID- 15153489
TI  - Expression of L-selectin, but not CD44, is required for early neutrophil
      extravasation in antigen-induced arthritis.
AB  - L (leukocyte)-selectin (CD62L) and CD44 are major adhesion receptors that support
      the rolling of leukocytes on endothelium, the first step of leukocyte entry into
      inflamed tissue. The specific contribution of L-selectin or CD44 to the
      regulation of cell traffic to joints in arthritis has not been investigated. We
      used CD44-deficient, L-selectin-deficient, and CD44/L-selectin double knockout
      mice to determine the requirement for these receptors for inflammatory cell
      recruitment during Ag-induced arthritis. Intraperitoneal immunization resulted in
      similar activation status and Ag-specific responses in wild-type and gene
      targeted mice. However, extravasation of neutrophil granulocytes, but not the
      emigration of T cells, into the knee joints after intra-articular Ag injection
      was significantly delayed in L-selectin-deficient and double knockout mice.
      Intravital videomicroscopy on the synovial microcirculation revealed enhanced
      leukocyte rolling and diminished adherence in mice lacking either CD44 or L
      selectin, but CD44 deficiency had no significant effect on the recruitment of L
      selectin-null cells. Compared with wild-type leukocytes, expression of L-selectin
      was down-regulated in CD44-deficient cells in the spleen, peripheral blood, and
      inflamed joints, suggesting that reduced expression of L-selectin, rather than
      the lack of CD44, could be responsible for the delayed influx of granulocytes
      into the joints of CD44-deficient mice. In conclusion, there is a greater
      requirement for L-selectin than for CD44 for neutrophil extravasation during the
      early phase of Ag-induced arthritis.

PMID- 15153491
TI  - Methylation of STAT6 modulates STAT6 phosphorylation, nuclear translocation, and
      DNA-binding activity.
AB  - Signal transducer and activator of transcription 6 is a transcription factor
      important for the development of Th2 cells and regulation of gene expression by
      IL-4 and IL-13. It has been reported that STAT1 activity is regulated by
      methylation of a conserved arginine residue in the N-terminal domain. Methylation
      of STAT6 has not yet been explored. We observed methylation of STAT6 in cells
      transfected with wild-type STAT6, but not in cells transfected with Arg(27)Ala
      mutant, confirming that STAT6 is methylated on Arg(27). Transfectants expressing
      mutant Arg(27)Ala STAT6 displayed markedly diminished IL-4-dependent STAT6
      phosphorylation and nuclear translocation, and no STAT6 DNA-binding activity
      compared with wild-type STAT6 transfectants. To confirm this, the experiments
      were repeated using inhibitors of methylation. In the presence of methylation
      inhibitors, STAT6 methylation was diminished, as was phosphorylation of STAT6 and
      STAT6 DNA-binding activity. Thus, methylation is a critical regulator of STAT6
      activity, necessary for optimal STAT6 phosphorylation, nuclear translocation, and
      DNA-binding activity. Furthermore, methylation of STAT6 has distinct effects from
      those reported with STAT1.

PMID- 15153490
TI  - A signal through OX40 (CD134) allows anergic, autoreactive T cells to acquire
      effector cell functions.
AB  - To study mechanisms of peripheral self-tolerance, we injected small numbers of
      naive CD4(+) TCR-transgenic T cells into mice expressing the MHC/peptide ligand
      under the control of an MHC class II promoter. The donor T cells expand rapidly
      to very large numbers, acquire memory markers, and go out into tissues, but the
      animals remain healthy, and the accumulated T cells are profoundly anergic to
      restimulation with Ag in vitro. Provision of a costimulatory signal by
      coinjection of an agonist Ab to OX40 (CD134), a TNFR family member expressed on
      activated CD4 T cells, results in death of the mice within 12 days. TCR
      transgenic T cells recovered at 5 days from anti-OX40-treated mice have a unique
      phenotype: they remain unresponsive to Ag in vitro, but they are larger, more
      granular, and strongly IL-2R positive. Some spontaneously secrete IFN-gamma
      directly ex vivo, and the majority make IFN-gamma in response to PMA and
      ionomycin. Although they are anergic by conventional tests requiring Ag
      recognition, they respond vigorously to cytokines, proliferating in response to
      IL-2, and secreting IFN-gamma when TCR signaling is bypassed with IL-12 and IL
      18. We conclude that the costimulatory signal through OX40 allows otherwise
      harmless, proliferating, autoreactive T cells to acquire effector cell functions.
      The ability of these T cells to respond to cytokines by synthesizing additional
      inflammatory cytokines without a TCR signal may drive the fatal pathogenic
      process in vivo.

PMID- 15153492
TI  - Comparative genomic analysis of two avian (quail and chicken) MHC regions.
AB  - We mapped two different quail Mhc haplotypes and sequenced one of them (haplotype
      A) for comparative genomic analysis with a previously sequenced haplotype of the
      chicken Mhc. The quail haplotype A spans 180 kb of genomic sequence, encoding a
      total of 41 genes compared with only 19 genes within the 92-kb chicken Mhc.
      Except for two gene families (B30 and tRNA), both species have the same basic set
      of gene family members that were previously described in the chicken "minimal
      essential" Mhc. The two Mhc regions have a similar overall organization but
      differ markedly in that the quail has an expanded number of duplicated genes with
      7 class I, 10 class IIB, 4 NK, 6 lectin, and 8 B-G genes. Comparisons between the
      quail and chicken Mhc class I and class II gene sequences by phylogenetic
      analysis showed that they were more closely related within species than between
      species, suggesting that the quail Mhc genes were duplicated after the separation
      of these two species from their common ancestor. The proteins encoded by the NK
      and class I genes are known to interact as ligands and receptors, but unlike in
      the quail and the chicken, the genes encoding these proteins in mammals are found
      on different chromosomes. The finding of NK-like genes in the quail Mhc strongly
      suggests an evolutionary connection between the NK C-type lectin-like superfamily
      and the Mhc, providing support for future studies on the NK, lectin, class I, and
      class II interaction in birds.

PMID- 15153493
TI  - Evidence that the long murine terminal deoxynucleotidyltransferase isoform plays
      no role in the control of V(D)J junctional diversity.
AB  - Two TdT isoforms have been found in the mouse. The short isoform is known to add
      N regions to gene segment junctions during V(D)J recombination, but the role of
      the long (TdTL) isoform is controversial. We have shown that TdTL, although
      endowed with terminal transferase activity, is thermally unstable and unable to
      add N regions in vivo. In this study, we demonstrate that TdTL is devoid of 3'-5'
      exonuclease activity, and provide an analysis of nucleotide deletion and addition
      patterns in large series of V(D)J coding joins, arguing against a role of TdTL in
      the control of junctional diversity in Igs and TCRs.

PMID- 15153494
TI  - Differential requirement for adapter proteins Src homology 2 domain-containing
      leukocyte phosphoprotein of 76 kDa and adhesion- and degranulation-promoting
      adapter protein in FcepsilonRI signaling and mast cell function.
AB  - The adapter molecule Src homology 2 (SH2) domain-containing leukocyte
      phosphoprotein of 76 kDa (SLP-76) is essential for FcepsilonRI-mediated
      signaling, degranulation and IL-6 production in mast cells. To test the
      structural requirements of SLP-76 in mast cell signaling and function, we have
      studied the functional responses of murine bone marrow-derived mast cells (BMMCs)
      expressing mutant forms of SLP-76. We found that the N-terminal tyrosines as well
      as the central proline-rich region of SLP-76 are required for participation of
      SLP-76 in FcepsilonRI-mediated signaling and function. The C-terminal SH2 domain
      of SLP-76 also contributes to optimal function of SLP-76 in mast cells. Another
      adapter molecule, adhesion- and degranulation-promoting adapter protein (ADAP),
      is known to bind the SH2 domain of SLP-76, and cell line studies have implicated
      ADAP in mast cell adhesion and FcepsilonRI-induced degranulation. Surprisingly,
      we found that mast cells lacking ADAP expression demonstrate no defects in
      FcepsilonRI-induced adhesion, granule release, or IL-6 production, and that ADAP
      deficient mice produce a normal passive systemic anaphylactic response. Thus,
      failure to bind ADAP does not underlie the functional defects exhibited by SLP-76
      SH2 domain mutant-expressing mast cells.

PMID- 15153495
TI  - Early target genes of IL-12 and STAT4 signaling in th cells.
AB  - IL-12 signaling through STAT4 is essential for induction of optimal levels of IFN
      gamma production and commitment of Th1 cells. The molecular mechanism that
      controls how IL-12 and STAT4 signaling induces Th1 differentiation is poorly
      described. To identify the early target genes of IL-12 and STAT4 signaling,
      oligonucleotide arrays were used to compare the gene expression profiles of wild
      type and STAT4-knockout murine Th cells during the early Th1 differentiation.
      According to the results, 20 genes were regulated in an IL-12- and STAT4
      dependent manner. Importantly, Ifngamma was clearly the first gene induced by IL
      12 in a STAT4-dependent manner. Most of the other defects in gene expression in
      STAT4-knockout cells were seen after 48 h of Th1 polarization. In addition to IL
      12 signaling mediated by STAT4, STAT4-independent induction of a number of genes
      was observed immediately in response to Th1 induction. This induction was at
      least in part driven by IFN-gamma independently of STAT4. Importantly, addition
      of exogenous IFN-gamma into Th1 cell cultures of STAT4-knockout cells restored
      the defect in IFN-gamma production further demonstrating the critical role of IFN
      gamma in early Th1 differentiation.

PMID- 15153496
TI  - Random screening of proteins for HLA-A*0201-binding nine-amino acid peptides is
      not sufficient for identifying CD8 T cell epitopes recognized in the context of
      HLA-A*0201.
AB  - HLA-A2 is the most frequent HLA molecule in Caucasians with HLA-A*0201
      representing the most frequent allele; it was also the first human HLA allele for
      which peptide binding prediction was developed. The Bioinformatics and Molecular
      Analysis Section of the National Institutes of Health (BIMAS) and the University
      of Tubingen (Syfpeithi) provide the most popular prediction algorithms of
      peptide/MHC interaction on the World Wide Web. To test these predictions, HLA
      A*0201-binding nine-amino acid peptides were searched by both algorithms in 19
      structural CMV proteins. According to Syfpeithi, the top 2% of predicted peptides
      should contain the naturally presented epitopes in 80% of predictions
      (www.syfpeithi.de). Because of the high number of predicted peptides, the
      analysis was limited to 10 randomly chosen proteins. The top 2% of peptides
      predicted by both algorithms were synthesized corresponding to 261 peptides in
      total. PBMC from 10 HLA-A*0201-positive and CMV-seropositive healthy blood donors
      were tested by ex vivo stimulation with all 261 peptides using crossover peptide
      pools. IFN-gamma production in T cells measured by CFC was used as readout.
      However, only one peptide was found to be stimulating in one single donor. As a
      result of this work, we report a potential new T cell target protein, one
      previously unknown CD8-T cell-stimulating peptide, and an extensive list of CMV
      derived potentially strong HLA-A*0201-binding peptides that are not recognized by
      T cells of HLA-A*0201-positive CMV-seropositive donors. We conclude that
      MHC/peptide binding predictions are helpful for locating epitopes in known target
      proteins but not necessarily for screening epitopes in proteins not known to be T
      cell targets.

PMID- 15153497
TI  - Characterization of the human Ig heavy chain antigen binding complementarity
      determining region 3 using a newly developed software algorithm, JOINSOLVER.
AB  - We analyzed 77 nonproductive and 574 productive human V(H)DJ(H) rearrangements
      with a newly developed program, JOINSOLVER. In the productive repertoire, the H
      chain complementarity determining region 3 (CDR3(H)) was significantly shorter
      (46.7 +/- 0.5 nucleotides) than in the nonproductive repertoire (53.8 +/- 1.9
      nucleotides) because of the tendency to select rearrangements with less TdT
      activity and shorter D segments. Using criteria established by Monte Carlo
      simulations, D segments could be identified in 71.4% of nonproductive and 64.4%
      of productive rearrangements, with a mean of 17.6 +/- 0.7 and 14.6 +/- 0.2
      retained germline nucleotides, respectively. Eight of 27 D segments were used
      more frequently than expected in the nonproductive repertoire, whereas 3 D
      segments were positively selected and 3 were negatively selected, indicating that
      both molecular mechanisms and selection biased the D segment usage. There was no
      bias for D segment reading frame (RF) use in the nonproductive repertoire,
      whereas negative selection of the RFs encoding stop codons and positive selection
      of RF2 that frequently encodes hydrophilic amino acids were noted in the
      productive repertoire. Except for serine, there was no consistent selection or
      expression of hydrophilic amino acids. A bias toward the pairing of 5' D segments
      with 3' J(H) segments was observed in the nonproductive but not the productive
      repertoire, whereas V(H) usage was random. Rearrangements using inverted D
      segments, DIR family segments, chromosome 15 D segments and multiple D segments
      were found infrequently. Analysis of the human CDR3(H) with JOINSOLVER has
      provided comprehensive information on the influences that shape this important Ag
      binding region of V(H) chains.

PMID- 15153498
TI  - Identification of protein-protein interfaces implicated in CD80-CD28
      costimulatory signaling.
AB  - The B7 ligands CD80 and CD86 on APCs deliver either costimulatory or inhibitory
      signals to the T cell when interacting with their counter-receptors CD28 and
      CD152 (CTLA-4) on the T cell surface. Although crucial for lymphocyte regulation,
      the structural basis of these interactions is still not completely understood.
      Using multivalent presentation and conditions mimicking clustering, believed to
      be essential for signaling through these receptors, and by applying a combined
      differential mass spectrometry and structural mapping approach to these
      conditions, we were able to identify a putative contact area involving
      hydrophilic regions on both CD28 and CD80 as well as a putative CD28
      oligomerization interface induced by B7 ligation. Analysis of the CD80-CD28
      interaction site reveals a well-defined interface structurally distinct from that
      of CD80 and CD152 and thus provides valuable information for therapeutic
      intervention targeted at this pathway, suggesting a general approach for other
      receptors.

PMID- 15153499
TI  - Linker for activation of B cells: a functional equivalent of a mutant linker for
      activation of T cells deficient in phospholipase C-gamma1 binding.
AB  - Adaptor proteins have important functions in coupling stimulation through
      immunoreceptors with downstream events. The adaptor linker for activation of B
      cells (LAB)/non-T cell activation linker (NTAL) is expressed in various immune
      cell types and has a similar domain structure as linker for activation of T cells
      (LAT). In this study we generated a LAB transgenic mouse to compare the
      functional differences between LAB and LAT. A LAB transgene expressed in LAT
      deficient T cells was able to restore T cell development. However, these mice
      developed severe organomegaly with disorganized lymphoid tissues. Lymphocytes
      from these transgenic mice were hyperactivated, and T cells produced large
      amounts of type II cytokines. In addition, these activities appeared to be
      uncoupled from the TCR. An examination of the signaling capabilities of these T
      cells revealed that LAB resembled a LAT molecule unable to bind phospholipase C
      gamma1.

PMID- 15153500
TI  - Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor
      8/IFN consensus sequence binding protein in dendritic cells.
AB  - Unmethylated CpG DNA binds to the Toll-like receptor 9 (TLR9) and activates NF
      kappaB to induce cytokine genes in dendritic cells (DCs). IFN regulatory factor
      (IRF)-8/IFN consensus sequence binding protein is a transcription factor
      important for development and activation of DCs. We found that DCs from IRF-8(-/
      ) mice were unresponsive to CpG and failed to induce TNF-alpha and IL-6, targets
      of NF-kappaB. Revealing a signaling defect selective for CpG, these cytokines
      were robustly induced in IRF-8(-/-) DCs in response to LPS that signals through
      TLR4. IRF-8(-/-) DCs expressed TLR9, adaptor myeloid differentiation factor 88,
      and other signaling molecules, but CpG failed to activate NF-kappaB in -/- cells.
      This was due to the selective inability of -/- DCs to activate I-kappaB kinase
      alphabeta, the kinases required for NF-kappaB in response to CpG. IRF-8
      reintroduction fully restored CpG activation of NF-kappaB and cytokine induction
      in -/- DCs. Together, TLR signals that activate NF-kappaB are diverse among
      different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs.

PMID- 15153501
TI  - Infection-induced expansion of a MHC Class Ib-dependent intestinal
      intraepithelial gammadelta T cell subset.
AB  - Salmonella species invade the host via the intestinal epithelium. Hence,
      intestinal intraepithelial lymphocytes (iIELs) are potentially the first element
      of the immune system to encounter Salmonella during infection. In this study, we
      demonstrate, in a mouse model, the expansion of a CD8alphabeta(+)CD94(
      )TCRgammadelta(+) T cell subset within the iIEL population in response to oral
      infection with virulent or avirulent Salmonella. This population can be detected
      3 days following infection, represents up to 15% of the TCRgammadelta(+) iIELs,
      and is dependent on the MHC class Ib molecule T23 (Qa-1). Qa-1 is expressed by
      intestinal epithelial cells and thus accessible for iIEL recognition. Such cells
      may play a role in the early immune response to Salmonella.

PMID- 15153502
TI  - Oligosaccharide side chains on human secretory IgA serve as receptors for ricin.
AB  - Secretory IgA (sIgA) Abs are polymeric Igs comprised of two or more IgA monomers
      joined together at their C termini and covalently associated with a 70-kDa
      glycoprotein called secretory component. As the predominant Ig type in
      gastrointestinal sections, sIgA Abs are centrally important in adaptive immunity
      to enteropathogenic bacteria, viruses, and toxins. In this study, we demonstrate
      that sIgA Abs may also function in innate defense against ricin, a naturally
      occurring, galactose-specific plant lectin with extremely potent shiga toxin-like
      enzymatic activity. In lectin blot overlay assays, we found that ricin bound to
      secretory component and the H chain of human IgA, and this binding was inhibited
      by the addition of excess galactose. The toxin also recognized IgM (albeit with
      less affinity than to IgA), but not IgG. Ricin bound to both human IgA1 and IgA2,
      primarily via N-linked oligosaccharide side chains. At 100-fold molar excess
      concentration, sIgA (but not IgG) Abs inhibited ricin attachment to the apical
      surfaces of polarized intestinal epithelial cells grown in culture. sIgA Abs also
      visibly reduced toxin binding to the luminal surfaces of human duodenum in tissue
      section overlay assays. We conclude that sIgA Abs in mucosal secretions may serve
      as receptor analogues for ricin, thereby reducing the effective dose of toxin
      capable of gaining access to glycolipid and glycoprotein receptors on epithelial
      cell surfaces.

PMID- 15153503
TI  - TNF influences chemokine expression of macrophages in vitro and that of CD11b+
      cells in vivo during Mycobacterium tuberculosis infection.
AB  - Granulomas, focal accumulations of immune cells, form in the lung during
      Mycobacterium tuberculosis infection. Chemokines, chemotactic cytokines, are
      logical candidates for inducing migration of T lymphocytes and monocytes to and
      within the lung. TNF influences chemokine expression in some models. TNF
      deficient mice infected with M. tuberculosis are highly susceptible to disease,
      and granuloma formation is inhibited. Through in vitro assays, we demonstrate
      that neutralization of TNF in M. tuberculosis-infected macrophages led to a
      reduction in many inflammatory chemokines, such as C-C chemokine ligand 5, CXC
      ligand 9 (CXCL9), and CXCL10. In TNF-deficient mice, immune cells migrated to the
      lungs early after infection, but did not organize to form granulomas within the
      lung. Although chemokine expression, as measured in whole lung tissue, was not
      different, the expression of chemokines in the CD11b(+) subset of cells isolated
      ex vivo from the lungs of TNF-deficient mice had reduced expression of C-C
      chemokine ligand 5, CXCL9, and CXCL10 at early time points after TNF
      neutralization. Local expression of CXCR3-binding chemokines within the lungs, as
      determined by in situ hybridization, was also affected by TNF. Therefore, TNF
      affects the expression of chemokines by macrophages in vitro and CD11b(+) cells
      in vivo, which probably influences the local chemokine gradients and granuloma
      formation.

PMID- 15153504
TI  - Bacterial ghosts are an efficient delivery system for DNA vaccines.
AB  - Mass implementation of DNA vaccines is hindered by the requirement of high
      plasmid dosages and poor immunogenicity. We evaluated the capacity of Mannheimia
      haemolytica ghosts as delivery system for DNA vaccines. In vitro studies showed
      that bacterial ghosts loaded with a plasmid carrying the green fluorescent
      protein-encoding gene (pEGFP-N1) are efficiently taken up by APC, thereby leading
      to high transfection rates (52-60%). Vaccination studies demonstrated that ghost
      mediated delivery by intradermal or i.m. route of a eukaryotic expression plasmid
      containing the gene coding for beta-galactosidase under the control of the CMV
      immediate early gene promoter (pCMVbeta) stimulates more efficient Ag-specific
      humoral and cellular (CD4(+) and CD8(+)) immune responses than naked DNA in
      BALB/c mice. The use of ghosts also allows modulating the major Th response from
      a mixed Th1/Th2 to a more dominant Th2 pattern. Intravenous immunization with
      dendritic cells loaded ex vivo with pCMVbeta-containing ghosts also resulted in
      the elicitation of beta-galactosidase-specific responses. This suggests that
      dendritic cells play an important role in the stimulation of immune responses
      when bacterial ghosts are used as a DNA delivery system. Bacterial ghosts not
      only target the DNA vaccine construct to APC, but also provide a strong danger
      signal, acting as natural adjuvants, thereby promoting efficient maturation and
      activation of dendritic cells. Thus, bacterial ghosts constitute a promising
      technology platform for the development of more efficient DNA vaccines.

PMID- 15153505
TI  - Pulmonary surfactant protein a inhibits macrophage reactive oxygen intermediate
      production in response to stimuli by reducing NADPH oxidase activity.
AB  - Alveolar macrophages are important host defense cells in the human lung that
      continuously phagocytose environmental and infectious particles that invade the
      alveolar space. Alveolar macrophages are prototypical alternatively activated
      macrophages, with up-regulated innate immune receptor expression, down-regulated
      costimulatory molecule expression, and limited production of reactive oxygen
      intermediates (ROI) in response to stimuli. Surfactant protein A (SP-A) is an
      abundant protein in pulmonary surfactant that has been shown to alter several
      macrophage (Mphi) immune functions. Data regarding SP-A effects on ROI production
      are contradictory, and lacking with regard to human Mphi. In this study, we
      examined the effects of SP-A on the oxidative response of human Mphi to
      particulate and soluble stimuli using fluorescent and biochemical assays, as well
      as electron paramagnetic resonance spectroscopy. SP-A significantly reduced Mphi
      superoxide production in response to the phorbol ester PMA and to serum-opsonized
      zymosan (OpZy), independent of any effect by SP-A on zymosan phagocytosis. SP-A
      was not found to scavenge superoxide. We measured Mphi oxygen consumption in
      response to stimuli using a new oxygen-sensitive electron paramagnetic resonance
      probe to determine the effects of SP-A on NADPH oxidase activity. SP-A
      significantly decreased Mphi oxygen consumption in response to PMA and OpZy.
      Additionally, SP-A reduced the association of NADPH oxidase component p47(phox)
      with OpZy phagosomes as determined by confocal microscopy, suggesting that SP-A
      inhibits NADPH oxidase activity by altering oxidase assembly on phagosomal
      membranes. These data support an anti-inflammatory role for SP-A in pulmonary
      homeostasis by inhibiting Mphi production of ROI through a reduction in NADPH
      oxidase activity.

PMID- 15153506
TI  - The upper and lower respiratory tracts differ in their requirement of IFN-gamma
      and IL-4 in controlling respiratory mycoplasma infection and disease.
AB  - The purpose of this study is to evaluate the significance of IFN-gamma and IL-4
      production in controlling mycoplasma infection and the pathogenesis of disease in
      the upper and lower respiratory tract. By using IFN-gamma knockout and IL-4
      knockout BALB/c mice, we were able to study the contribution of these cytokines
      in the development of pathogenesis and/or protection in response to mycoplasma
      respiratory infection, in both the upper and lower respiratory tracts. The loss
      of either IFN-gamma or IL-4 does not affect disease pathogenesis or mycoplasma
      organism numbers in the upper respiratory tract. However, in the absence of IL-4,
      the nasal passages developed a compensatory immune response, characterized by
      higher numbers of macrophages and CD8(+) T cells, which may be masking
      detrimental effects due to IL-4 deficiency. This is in contrast to the lower
      respiratory tract, where the loss of IFN-gamma, but not IL-4, leads to higher
      mycoplasma numbers and increased disease severity. The loss of IFN-gamma impacted
      the innate immune system's ability to effectively clear mycoplasma, as the number
      of organisms was higher by day 3 postinfection. This higher organism burden most
      likely impacted disease pathogenesis; however, the development of Th2 cell
      mediated adaptive immune response most likely contributed to lesion severity at
      later time points during infection. Our studies demonstrate that the upper and
      lower respiratory tracts are separate and distinct in their cytokine requirements
      for generating immunity against mycoplasma infection.

PMID- 15153507
TI  - Massive number of antigen-specific CD4 T cells during vaccination with live
      attenuated Salmonella causes interclonal competition.
AB  - The clonal burst size of CD4 T cells is predicted to be less than that of CD8 T
      cells. In this study, we demonstrate that massive numbers of Ag-specific CD4 T
      cells respond during vaccination of mice with live attenuated Salmonella,
      reaching a peak frequency of approximately 50% of CD4 T cells. Salmonella
      specific T cells persisted at high frequency for several weeks and could be
      detected in the memory population for months after infection. Surprisingly, the
      expansion of endogenous Salmonella-specific CD4 T cells prevented the persistence
      of adoptively transferred Salmonella-specific T cells in vivo, demonstrating
      interclonal competition for access to the memory compartment.

PMID- 15153508
TI  - Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia
      infection.
AB  - To address the role of cellular immunity during ehrlichia infection, we have used
      a newly described model of monocytic ehrlichiosis that results from infection of
      mice by an ehrlichia that was isolated from an Ixodes ovatus tick (Ixodes ovatus
      ehrlichia, IOE). Immunocompetent C57BL/6 and BALB/c mice exhibited a dose
      dependent susceptibility to IOE infection. Mice infected with a high dose
      inoculum ( approximately 1000 organisms) exhibited pronounced thrombocytopenia,
      lymphopenia, anemia, and morbidity within 12 days postinfection. Infection was
      associated with bacterial colonization of a number of tissues. In contrast, mice
      infected with a low dose inoculum ( approximately 100 organisms) exhibited only
      transient disease and were able to resolve the infection. SCID mice were highly
      susceptible to low-dose infection, indicating that adaptive immunity was
      required. Resistance to sublethal challenge in both C57BL/6 and BALB/c mice was
      CD4-, but not CD8-, dependent and required IL-12p40-dependent cytokines, IFN
      gamma, and TNF-alpha, but not IL-4. CD4 T cells purified from infected mice
      proliferated in vitro in response to IOE Ags. T cell proliferation was associated
      with production of IFN-gamma, and the production of this cytokine by CD4 T cells
      rescued IFN-gamma-deficient mice from fatal infection. Exogenous IFN-gamma was
      capable of inducing microbiocidal activity in infected macrophages. The data
      suggest that classical immune mechanisms involving CD4 cells and type 1 cytokines
      are responsible for macrophage activation and for elimination of this
      intracellular bacterial pathogen.

PMID- 15153509
TI  - Molecular determinants regulating the pairing of NKG2 molecules with CD94 for
      cell surface heterodimer expression.
AB  - The lytic capacity of a NK cell is regulated, in part, by the balance in cell
      surface expression between inhibitory CD94/NKG2A and activating CD94/NKG2C
      heterodimers. We demonstrate that, in the absence of DAP12, rhesus monkey NKG2A
      is preferentially expressed at the cell surface with CD94 due to a single amino
      acid difference in the transmembrane of NKG2A and NKG2C. Furthermore, in the
      context of an NKG2A transmembrane, the stalk domain of NKG2C was found to enhance
      heterodimer formation with CD94 compared with the stalk domain of NKG2A. In the
      presence of DAP12, the ability of NKG2C to compete for cell surface CD94
      heterodimerization is enhanced and approaches that of NKG2A. Finally, allelic
      differences that affect the ability of rhesus NKG2A to reach the cell surface
      with CD94 could also be mapped to the transmembrane. These differences in the
      ability of inhibitory and activating NKG2 molecules to reach the cell surface
      provide a mechanism for the regulation of NK cell activity.

PMID- 15153510
TI  - Induction of in vivo functional Db-restricted cytolytic T cell activity against a
      putative phosphate transport receptor of Mycobacterium tuberculosis.
AB  - Using plasmid vaccination with DNA encoding the putative phosphate transport
      receptor PstS-3 from Mycobacterium tuberculosis and 36 overlapping 20-mer
      peptides spanning the entire PstS-3 sequence, we determined the immunodominant
      Th1-type CD4(+) T cell epitopes in C57BL/10 mice, as measured by spleen cell IL-2
      and IFN-gamma production. Furthermore, a potent IFN-gamma-inducing, D(b)
      restricted CD8(+) epitope was identified using MHC class I mutant B6.C-H-2(bm13)
      mice and intracellular IFN-gamma and whole blood CD8(+) T cell tetramer staining.
      Using adoptive transfer of CFSE-labeled, peptide-pulsed syngeneic spleen cells
      from naive animals into DNA vaccinated or M. tuberculosis-infected recipients, we
      demonstrated a functional in vivo CTL activity against this D(b)-restricted PstS
      3 epitope. IFN-gamma ELISPOT responses to this epitope were also detected in
      tuberculosis-infected mice. The CD4(+) and CD8(+) T cell epitopes defined for
      PstS-3 were completely specific and not recognized in mice vaccinated with either
      PstS-1 or PstS-2 DNA. The H-2 haplotype exerted a strong influence on immune
      reactivity to the PstS-3 Ag, and mice of the H-2(b, p, and f) haplotype produced
      significant Ab and Th1-type cytokine levels, whereas mice of H-2(d, k, r, s, and
      q) haplotype were completely unreactive. Low responsiveness against PstS-3 in MHC
      class II mutant B6.C-H-2(bm12) mice could be overcome by DNA vaccination. IFN
      gamma-producing CD8(+) T cells could also be detected against the D(b)-restricted
      epitope in H-2(p) haplotype mice. These results highlight the potential of DNA
      vaccination for the induction and characterization of CD4(+) and particularly
      CD8(+) T cell responses against mycobacterial Ags.

PMID- 15153511
TI  - Flagellin promotes myeloid differentiation factor 88-dependent development of Th2
      type response.
AB  - Activation of dendritic cells (DC) by microbial products via Toll-like receptors
      (TLR) is instrumental in the induction of immunity. In particular, TLR signaling
      plays a major role in the instruction of Th1 responses. The development of Th2
      responses has been proposed to be independent of the adapter molecule myeloid
      differentiation factor 88 (MyD88) involved in signal transduction by TLRs. In
      this study we show that flagellin, the bacterial stimulus for TLR5, drives MyD88
      dependent Th2-type immunity in mice. Flagellin promotes the secretion of IL-4 and
      IL-13 by Ag-specific CD4(+) T cells as well as IgG1 responses. The Th2-biased
      responses are associated with the maturation of DCs, which are shown to express
      TLR5. Flagellin-mediated DC activation requires MyD88 and induces NF-kappaB
      dependent transcription and the production of low levels of proinflammatory
      cytokines. In addition, the flagellin-specific response is characterized by the
      lack of secretion of the Th1-promoting cytokine IL-12 p70. In conclusion, this
      study suggests that flagellin and, more generally, TLR ligands can control Th2
      responses in a MyD88-dependent manner.

PMID- 15153512
TI  - Altered EBV viral load setpoint after HIV seroconversion is in accordance with
      lack of predictive value of EBV load for the occurrence of AIDS-related non
      Hodgkin lymphoma.
AB  - In contrast to the situation in the post-transplant setting, in HIV-infected
      individuals an elevated EBV load is not predictive of EBV-related malignancies.
      To study whether a high EBV load is already a normal situation early in HIV
      infection and is not related to a decrease in immune function over time, we
      investigated EBV load and EBV-specific CD8(+) T cells approximately 1 year before
      and 1 year after HIV seroconversion. EBV load significantly increased after HIV
      seroconversion from 205 to 1002 copies/10(6) PBMC (p < 0.001), whereas no further
      increase in EBV load was observed between 1 and 5 years after HIV seroconversion
      (median, 1827-2478 copies/10(6) PBMC; p = 0.530). Interestingly, the absolute
      number of EBV lytic epitope, RAKFKQLL-specific CD8(+) T cells increased over HIV
      seroconversion (4.78 to 9.54/ micro l; p = 0.011). Furthermore, the fraction of
      CD27-negative effector, RAK-specific CD8(+) T cells tended to increase (from 12.2
      to 17.31% CD27(-); p = 0.051), in accordance with Ag-driven differentiation. In
      conclusion, both virological and immunological data support the idea that a new
      EBV viral setpoint is reached early in HIV infection, probably by EBV
      reactivation, as suggested by the preferential increase in EBV lytic epitope
      specific CD8(+) T cells. These data may thus help to explain the lack of
      predictive value of EBV load for the occurrence of AIDS-related lymphoma.

PMID- 15153513
TI  - Healthy individuals that control a latent infection with Mycobacterium
      tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL
      4delta2.
AB  - The majority of healthy individuals exposed to Mycobacterium tuberculosis will
      not develop disease and identifying what constitutes "protective immunity" is one
      of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is
      essential for protection, but it is also apparent that IFN-gamma levels alone do
      not explain the immunity/susceptibility dichotomy. The controversy regarding
      correlates of immunity persists because identifying infected but healthy
      individuals (those who are immune) has been problematic. We have therefore used
      recognition of the M. tuberculosis virulence factor early secretory antigenic
      target 6 to identify healthy, but infected individuals from tuberculosis (TB)
      endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals
      for cytokines expressed directly ex vivo with the pattern found in TB patients.
      We find that TB patients are characterized by decreased levels of Th1 cytokines
      and increased levels of IL-10 compared with the healthy infected and noninfected
      community controls. Interestingly, the healthy infected subjects exhibited a
      selective increase of message for the IL-4 antagonist, IL-4delta2, compared with
      both TB patients or noninfected individuals. These data suggest that long-term
      control of M. tuberculosis infection is associated not just with elevated Th1
      responses but also with inhibition of the Th2 response.

PMID- 15153514
TI  - Murine cytomegalovirus interference with antigen presentation has little effect
      on the size or the effector memory phenotype of the CD8 T cell response.
AB  - As with most herpesviruses, CMVs encode viral genes that inhibit Ag presentation
      to CD8 T cells (VIPRs). VIPR function has been assumed to be essential for CMV to
      establish its characteristic lifetime infection of its host. We compared
      infection of C57BL/6 mice with wild-type murine CMV (MCMV) and a virus lacking
      each of MCMV's three known VIPRs: m4, m6, and m152. During acute infection, there
      was very little difference between the two viruses with respect to the kinetics
      of viral replication and clearance, or in the size and kinetics of the virus
      specific CD8 T cell response. During chronic infection, a large, effector memory,
      virus-specific CD8 T cell population (CD8(low)CD62L(-)CD11c(+)NKG2A(+)) was
      maintained in both infections; the size and phenotype of the CD8 T cell response
      to both viruses was remarkably similar. The characteristic effector memory
      phenotype of the CD8 T cells suggested that both wild-type and Deltam4+m6+m152
      virus continued to present Ag to CD8 T cells during the chronic phase of
      infection. During the chronic phase of infection, MCMV cannot be isolated from
      immunocompetent mice. However, upon immunosuppression, both Deltam4+m6+m152 and
      wild-type virus could be reactivated from mice infected for 6 wk. Thus, restoring
      the ability of CD8 T cells to detect MCMV had little apparent effect on the
      course of MCMV infection and on the CD8 T cell response to it. These results
      challenge the notion that VIPR function is necessary for CMV persistence in the
      host.

PMID- 15153515
TI  - Toxoplasma gondii triggers myeloid differentiation factor 88-dependent IL-12 and
      chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct
      parasite molecules and host receptors.
AB  - Toll-like receptors (TLR) that signal through the common adaptor molecule myeloid
      differentiation factor 88 (MyD88) are essential in proinflammatory cytokine
      responses to many microbial pathogens. In this study we report that Toxoplasma
      gondii triggers neutrophil IL-12 and chemokine ligand 2 (CCL2; monocyte
      chemoattractant protein 1) production in strict dependence upon functional MyD88.
      Nevertheless, the responses are distinct. Although we identify TLR2 as the
      receptor triggering CCL2 production, parasite-induced IL-12 release did not
      involve this TLR. The production of both IL-12 and CCL2 was increased after
      neutrophil activation with IFN-gamma. However, the synergistic effect of IFN
      gamma on IL-12, but not CCL2, was dependent upon Stat1 signal transduction.
      Although IL-10 was a potent down-regulator of Toxoplasma-triggered neutrophil IL
      12 release, the cytokine had no effect on parasite-induced CCL2 production.
      Soluble tachyzoite Ag fractionation demonstrated that CCL2- and IL-12 inducing
      activities are biochemically distinct. Importantly, Toxoplasma cyclophilin-18, a
      molecule previously shown to induce dendritic cell IL-12, was not involved in
      neutrophil IL-12 production. Our results show for the first time that T. gondii
      possesses multiple molecules triggering distinct MyD88-dependent signaling
      cascades, that these pathways are independently regulated, and that they lead to
      distinct profiles of cytokine production.

PMID- 15153516
TI  - C3a enhances nerve growth factor-induced NFAT activation and chemokine production
      in a human mast cell line, HMC-1.
AB  - Activation of cell surface G protein-coupled receptors leads to
      transphosphorylation and activation of a number of receptor tyrosine kinases.
      Human mast cells express G protein-coupled receptors for the complement component
      C3a (C3aR) and high affinity nerve growth factor (NGF) receptor tyrosine kinase,
      TrkA. To determine whether C3a cross-regulates TrkA signaling and biological
      responses, we used a human mast cell-line, HMC-1, that natively expresses both
      receptors. We found that NGF caused tyrosine phosphorylation of TrkA, resulting
      in a sustained Ca(2+) mobilization, NFAT activation, extracellular-signal
      regulated kinase (ERK) phosphorylation, and chemokine, macrophage inflammatory
      protein-1beta (MIP-1beta) production. In contrast, C3a induced a transient Ca(2+)
      mobilization and ERK phosphorylation but failed to stimulate TrkA
      phosphorylation, NFAT activation, or MIP-1beta production. Surprisingly, C3a
      significantly enhanced NGF-induced NFAT activation, ERK phosphorylation, and MIP
      1beta production. Pertussis toxin, a G(i/o) inhibitor, selectively blocked
      priming by C3a but had no effect on NGF-induced responses. Mitogen-activated
      protein/ERK kinase inhibitor U0126 caused approximately 30% inhibition of NGF
      induced MIP-1beta production but had no effect on priming by C3a. However,
      cyclosporin A, an inhibitor of calcineurin-mediated NFAT activation, caused
      substantial inhibition of NGF-induced MIP-1beta production both in the absence
      and presence of C3a. These data demonstrate that NGF caused tyrosine
      phosphorylation of TrkA to induce chemokine production in HMC-1 cells via a
      pathway that mainly depends on sustained Ca(2+) mobilization and NFAT activation.
      Furthermore, C3a enhances NGF-induced transcription factor activation and
      chemokine production via a G protein-mediated pathway that does not involve TrkA
      phosphorylation.

PMID- 15153517
TI  - Suppressors of cytokine signaling regulate Fc receptor signaling and cell
      activation during immune renal injury.
AB  - Suppressors of cytokine signaling (SOCS) are cytokine-inducible proteins that
      modulate receptor signaling via tyrosine kinase pathways. We investigate the role
      of SOCS in renal disease, analyzing whether SOCS regulate IgG receptor (FcgammaR)
      signal pathways. In experimental models of immune complex (IC)
      glomerulonephritis, the renal expression of SOCS family genes, mainly SOCS-3,
      significantly increased, in parallel with proteinuria and renal lesions, and the
      proteins were localized in glomeruli and tubulointerstitium. Induction of
      nephritis in mice with a deficiency in the FcgammaR gamma-chain (gamma(-/-) mice)
      resulted in a decrease in the renal expression of SOCS-3 and SOCS-1. Moreover,
      blockade of FcgammaR by Fc fragment administration in rats with ongoing nephritis
      selectively inhibited SOCS-3 and SOCS-1, without affecting cytokine-inducible Src
      homology 2-containing protein and SOCS-2. In cultured human mesangial cells (MC)
      and monocytes, IC caused a rapid and transient induction of SOCS-3 expression.
      Similar kinetics was observed for SOCS-1, whereas SOCS-2 expression was very low.
      MC from gamma(-/-) mice failed to respond to IC activation, confirming the
      participation of FcgammaR. Interestingly, IC induced tyrosine phosphorylation of
      SOCS-3 and Tec tyrosine kinase, and both proteins coprecipitated in lysates from
      IC-stimulated MC, suggesting intracellular association. IC also activated STAT
      pathway in MC, which was suppressed by SOCS overexpression, mainly SOCS-3. In
      SOCS-3 knockdown studies, specific antisense oligonucleotides inhibited mesangial
      SOCS-3 expression, leading to an increase in the IC-induced STAT activation. Our
      results indicate that SOCS may play a regulatory role in FcgammaR signaling, and
      implicate SOCS as important modulators of cell activation during renal
      inflammation.

PMID- 15153518
TI  - Toll-like receptor 4 signaling by intestinal microbes influences susceptibility
      to food allergy.
AB  - The mechanisms by which signaling by the innate immune system controls
      susceptibility to allergy are poorly understood. In this report, we show that
      intragastric administration of a food allergen with a mucosal adjuvant induces
      allergen-specific IgE, elevated plasma histamine levels, and anaphylactic
      symptoms in three different strains of mice lacking a functional receptor for
      bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic
      controls. Susceptibility to allergy correlates with a Th2-biased cytokine
      response in both the mucosal (mesenteric lymph node and Peyer's patch) and
      systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are
      not inherently impaired in their ability to regulate Th1 cytokine production
      because they respond to stimulation via TLR9. Coadministration of CpG
      oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus
      CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1
      polarized cytokine response. When the composition of the bacterial flora is
      reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4
      wild-type mice become as susceptible to the induction of allergy as their TLR4
      mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are
      reduced in antibiotic-treated mice in which the flora has been allowed to
      repopulate. Taken together, our results suggest that TLR4-dependent signals
      provided by the intestinal commensal flora inhibit the development of allergic
      responses to food Ags.

PMID- 15153519
TI  - Volume-sensitive chloride channels do not mediate activation-induced chloride
      efflux in human neutrophils.
AB  - Many agents that activate neutrophils, enabling them to adhere to venular walls
      at sites of inflammation, cause a rapid Cl(-) efflux. This Cl(-) efflux and the
      increase in the number and affinity of beta(2) integrin surface adhesion
      molecules (up-regulation) are all inhibited by ethacrynic acid and certain
      aminomethyl phenols. The effectiveness of the latter compounds correlates with
      their inhibition of swelling-activated Cl(-) channels (I(Clvol)), suggesting that
      I(Clvol) mediates the activator-induced Cl(-) efflux. To test this hypothesis, we
      used whole-cell patch clamp in hypotonic media to examine the effects of
      inhibitors of up-regulation on I(Clvol) in neutrophils and promyelocytic leukemic
      HL-60 cells. Both the channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid
      and [3-methyl-1-p-sulfophenyl-5-pyrazolone-(4)]-[1,3-dibutylbarbituric acid]
      pentamethine oxonol (WW781), a nonpenetrating oxonol, inhibited I(Clvol) at
      concentrations similar to those that inhibit beta(2) integrin up-regulation.
      However, ethacrynic acid, at the same concentration that inhibits activator
      induced Cl(-) efflux and up-regulation, had no effect on I(Clvol) and swelling
      activated Cl(-) efflux, providing evidence against the involvement of I(Clvol) in
      the activator-induced Cl(-) efflux.

PMID- 15153520
TI  - Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the
      C5a and formylated peptide receptor.
AB  - Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is an exoprotein
      produced by several strains of S. aureus, and a potent inhibitor of neutrophil
      and monocyte chemotaxis toward C5a and formylated peptides like fMLP. These
      chemoattractants act on their target cells by binding and activating the C5aR and
      formylated peptide receptor (FPR), respectively. In the present report, we
      examined the mechanism by which CHIPS affects both of these receptors. We showed
      that CHIPS blocked binding of anti-C5aR mAb and formylated peptide to human
      neutrophils as efficiently at temperatures of 0 and 37 degrees C, implying that
      it is independent of signal transducing systems. This was confirmed by showing
      that CHIPS acts completely independently of ATP. Additionally, CHIPS was not
      internalized upon binding to neutrophils. Furthermore, we showed that CHIPS binds
      specifically to the C5aR and FPR expressed on U937 cells. This binding was
      functional in blocking C5a- and fMLP-induced calcium mobilization in these cell
      lines. These results suggest that CHIPS binds directly to the C5aR and FPR,
      thereby preventing the natural ligands from activating these receptors. The
      apparent K(d) values of CHIPS for the C5aR and FPR were 1.1 +/- 0.2 nM and 35.4
      +/- 7.7 nM, respectively. Moreover, after screening a wide variety of other G
      protein-coupled receptors, CHIPS was found to affect exclusively the C5aR and
      FPR. This selectivity and high-affinity binding with potent antagonistic effects
      makes CHIPS a promising lead for the development of new anti-inflammatory
      compounds for diseases in which damage by neutrophils plays a key role.

PMID- 15153521
TI  - TL1A synergizes with IL-12 and IL-18 to enhance IFN-gamma production in human T
      cells and NK cells.
AB  - TL1A, a recently described TNF-like cytokine that interacts with DR3,
      costimulates T cells and augments anti-CD3 plus anti-CD28 IFN-gamma production.
      In the current study we show that TL1A or an agonistic anti-DR3 mAb synergize
      with IL-12/IL-18 to augment IFN-gamma production in human peripheral blood T
      cells and NK cells. TL1A also enhanced IFN-gamma production by IL-12/IL-18
      stimulated CD56(+) T cells. When expressed as fold change, the synergistic effect
      of TL1A on cytokine-induced IFN-gamma production was more pronounced on CD4(+)
      and CD8(+) T cells than on CD56(+) T cells or NK cells. Intracellular cytokine
      staining showed that TL1A significantly enhanced both the percentage and the mean
      fluorescence intensity of IFN-gamma-producing T cells in response to IL-12/IL-18.
      The combination of IL-12 and IL-18 markedly up-regulated DR3 expression in NK
      cells, whereas it had minimal effect in T cells. Our data suggest that TL1A/DR3
      pathway plays an important role in the augmentation of cytokine-induced IFN-gamma
      production in T cells and that DR3 expression is differentially regulated by IL
      12/IL-18 in T cells and NK cells.

PMID- 15153522
TI  - Role of calcium in pancreatic islet cell death by IFN-gamma/TNF-alpha.
AB  - We studied the intracellular events associated with pancreatic beta cell
      apoptosis by IFN-gamma/TNF-alpha synergism. IFN-gamma/TNF-alpha treatment of
      MIN6N8 insulinoma cells increased the amplitude of high voltage-activated Ca(2+)
      currents, while treatment with IFN-gamma or TNF-alpha alone did not. Cytosolic
      Ca(2+) concentration ([Ca(2+)](c)) was also increased by IFN-gamma/TNF-alpha
      treatment. Blockade of L-type Ca(2+) channel by nifedipine abrogated death of
      insulinoma cells by IFN-gamma/TNF-alpha. Diazoxide that attenuates voltage
      activated Ca(2+) currents inhibited MIN6N8 cell death by IFN-gamma/TNF-alpha,
      while glibenclamide that accentuates voltage-activated Ca(2+) currents augmented
      insulinoma cell death. A protein kinase C inhibitor attenuated MIN6N8 cell death
      and the increase in [Ca(2+)](c) by IFN-gamma/TNF-alpha. Following the increase in
      [Ca(2+)](c), calpain was activated, and calpain inhibitors decreased insulinoma
      cell death by IFN-gamma/TNF-alpha. As a downstream of calpain, calcineurin was
      activated and the inhibition of calcineurin activation by FK506 diminished
      insulinoma cell death by IFN-gamma/TNF-alpha. BAD phosphorylation was decreased
      by IFN-gamma/TNF-alpha because of the increased calcineurin activity, which was
      reversed by FK506. IFN-gamma/TNF-alpha induced cytochrome c translocation from
      mitochondria to cytoplasm and activation of caspase-9. Effector caspases such as
      caspase-3 or -7 were also activated by IFN-gamma/TNF-alpha treatment. These
      results indicate that IFN-gamma/TNF-alpha synergism induces pancreatic beta cell
      apoptosis by Ca(2+) channel activation followed by downstream intracellular
      events such as mitochondrial events and caspase activation and also suggest the
      therapeutic potential of Ca(2+) modulation in type 1 diabetes.

PMID- 15153523
TI  - TGF-beta1 represses activation and resultant death of microglia via inhibition of
      phosphatidylinositol 3-kinase activity.
AB  - Overactivation of microglial cells may cause severe brain tissue damage in
      various neurodegenerative diseases. Therefore, the overactivation of microglia
      should be repressed by any means. The present study investigated the potential
      mechanism and signaling pathway for the repressive effect of TGF-beta1, a major
      anti-inflammatory cytokine, on overactivation and resultant death of microglial
      cells. A bacterial endotoxin LPS stimulated expression of inducible NO synthase
      (iNOS) and caused death in cultured microglial cells. TGF-beta1 markedly blocked
      these LPS effects. However, the LPS-evoked death of microglial cells was not
      solely attributed to excess production of NO. Because phosphatidylinositol 3
      kinase (PI3K) was previously shown to play a crucial role in iNOS expression and
      cell survival signals, we further studied whether PI3K signaling was associated
      with the suppressive effect of TGF-beta1. Like TGF-beta1, the PI3K inhibitor
      LY294002 blocked iNOS expression and death in cultured microglial cells. Both TGF
      beta1 and LY294002 decreased the activation of caspases 3 and 11 and the mRNA
      expression of various kinds of inflammatory molecules caused by LPS. TGF-beta1
      was further found to decrease LPS-induced activation of PI3K and Akt. TGF-beta1
      and LY294002 suppressed LPS-induced p38 mitogen-activated kinase and c-Jun N
      terminal kinase activity. In contrast, TGF-beta1 and LY294002 enhanced LPS
      induced NF-kappaB activity. Our data indicate that TGF-beta1 protect normal or
      damaged brain tissue by repressing overactivation of microglial cells via
      inhibition of PI3K and its downstream signaling molecules.

PMID- 15153524
TI  - Bid truncation, bid/bax targeting to the mitochondria, and caspase activation
      associated with neutrophil apoptosis are inhibited by granulocyte colony
      stimulating factor.
AB  - Neutrophil apoptosis constitutes a way of managing neutrophil-mediated reactions.
      It allows coping with infections, but avoiding overt bystander tissue damage.
      Using digitonin-based subcellular fractionation and Western blotting, we found
      that spontaneous apoptosis of human neutrophils (after approximately 20 h of
      culture) was associated with translocation of two proapoptotic Bcl-2 homologues,
      Bid and Bax, to the mitochondria and truncation of Bid, with subsequent release
      of Omi/HtrA2 and Smac/DIABLO into the cytosol. These events were accompanied by
      processing and increased enzymatic activity of caspase-8, -9, and -3. A G-CSF
      mediated reduction in apoptosis coincided with inhibition of all these reactions.
      The G-CSF-induced effects were differentially dependent on newly synthesized
      mediators. Whereas inhibition of Bax targeting to the mitochondria and inhibition
      of caspase activation by G-CSF were dependent on protein synthesis, Bid
      truncation and redistribution were prevented by G-CSF regardless of the presence
      of the protein synthesis inhibitor cycloheximide. Apparently, the observed Bid
      changes were dispensable for neutrophil apoptosis. Although the regulators of the
      inhibitor of apoptosis proteins (IAPs), Omi/HtrA2 and Smac/DIABLO, were released
      into the cytosol during apoptosis, we did not observe cleavage of X-linked IAP,
      which suggests that another mechanism of IAP deactivation is involved. Together
      our results support an integrative role of the mitochondria in induction and/or
      amplification of caspase activity and show that G-CSF may act by blocking Bid/Bax
      redistribution and inhibiting caspase activation.

PMID- 15153525
TI  - Distinct transcriptional programs activated by interleukin-10 with or without
      lipopolysaccharide in dendritic cells: induction of the B cell-activating
      chemokine, CXC chemokine ligand 13.
AB  - To understand the modulation of dendritic cell (DC) function by IL-10, gene
      expression profiling was performed by using Affymetrix technology (Santa Clara,
      CA) in human monocyte-derived DC treated with IL-10, alone or in combination with
      LPS. The modulation of selected genes was validated by real-time PCR, Northern
      blot, and protein production. IL-10 regulated in DC the expression of a limited
      number of genes, including IL-7, the receptors for transferrin and vitamin D(3),
      structural matrix proteins, and signal transduction elements. The combined
      treatment with LPS plus IL-10 modulated a number of genes comparable to LPS
      alone, but the expression profiles were distinct. As expected, IL-10 suppressed
      the expression of several LPS-inducible proinflammatory molecules. Among genes
      uniquely modulated by the concomitant treatment with LPS plus IL-10,
      phosphatidylinositol 3-kinase gamma was down-regulated while the suppressor of
      cytokine signaling 3, signaling lymphocytic activation molecule, regulator of G
      protein signaling 16, and the chemokine, CXC chemokine ligand (CXCL) 13, were up
      regulated. Overall, four distinct transcriptional programs were identified,
      related to: 1) control of immunity and inflammation; 2) tuning of cytokine
      receptor and G protein-coupled receptor signaling; 3) remodeling of extracellular
      matrix; and 4) B cell function and lymphoid tissue neogenesis. Among the latter
      genes, we further demonstrate that IL-10 synergizes with TLR ligands for the
      production of functionally active B cell-attracting chemokine, CXCL13, in both
      myeloid and plasmacytoid DC. This novel finding reveals that IL-10 sustains
      humoral immunity by inducing the production in APCs of the chemokine, CXCL13,
      which amplifies B cell recruitment and promotes lymphoid tissue neogenesis.

PMID- 15153526
TI  - Effects of TNF-alpha and IFN-gamma on nitric oxide-induced neurotoxicity in the
      mouse brain.
AB  - The present study investigated the interaction between highly reactive gaseous
      free radical NO and cytokines that are produced by activated Th-1 cells on the
      cerebral immune response and neuronal integrity. CD-1 mice received an
      intrastriatal infusion of different solutions containing the NO synthase
      inhibitor N(G)-nitro-L-arginine methylester, NO-releasing substance sodium
      nitroprusside (SNP), IFN-gamma, and/or TNF-alpha. The solution containing both
      cytokines caused a profound and transient transcriptional activation of numerous
      genes encoding proinflammatory proteins in microglial/monocytic cells ipsilateral
      to infusion site. This increase in gene expression peaked 1 day after the
      cerebral bolus of cytokines and returned to basal levels from 3 to 7 days post
      administration. N(G)-nitro-L-arginine methylester further stimulated this immune
      reaction to IFN-gamma and TNF-alpha, but the brain of these mice failed to
      exhibit signs of neurodegeneration and demyelination. In contrast, a single bolus
      of SNP in the striatal region caused neuronal death and demyelination as early as
      1 to 3 days following the infusion with the NO donor. This phenomenon was greatly
      exacerbated by the coadministration of both cytokines, although TNF-alpha
      remained the most critical cytokine to enhance the damage of cerebral elements.
      These data provide evidence that NO has the ability to modulate the immune
      response, which is not by itself detrimental for the brain. However, SNP-induced
      NO production together with TNF-alpha in the cerebral environment are critical
      events leading to intense neurodegeneration and demyelination in vivo.

PMID- 15153527
TI  - Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor
      U0126 in an asthma mouse model.
AB  - Mitogen-activated protein kinase (MAPK) signaling cascade plays a pivotal role in
      the activation of inflammatory cells. Recent findings revealed that the activity
      of p42/44 MAPK (also known as extracellular signal-regulated kinase (ERK)) in the
      lungs was significantly higher in asthmatic mice than in normal controls. We
      hypothesized that inhibition of ERK activity may have anti-inflammatory effects
      in allergic asthma. BALB/c mice were sensitized with OVA and, upon OVA aerosol
      challenge, developed airway eosinophilia, mucus hypersecretion, elevation in
      cytokine and chemokine levels, up-regulation of VCAM-1 expression, and airway
      hyperresponsiveness. Intraperitoneal administration of U0126, a specific MAPK/ERK
      kinase inhibitor, significantly (p < 0.05) inhibited OVA-induced increases in
      total cell counts, eosinophil counts, and IL-4, IL-5, IL-13, and eotaxin levels
      recovered in bronchoalveolar lavage fluid in a dose-dependent manner. U0126 also
      substantially (p < 0.05) reduced the serum levels of total IgE and OVA-specific
      IgE and IgG1. Histological studies show that U0126 dramatically inhibited OVA
      induced lung tissue eosinophilia, airway mucus production, and expression of VCAM
      1 in lung tissues. In addition, U0126 significantly (p < 0.05) suppressed OVA
      induced airway hyperresponsiveness to inhaled methacholine in a dose-dependent
      manner. Western blot analysis of whole lung lysates shows that U0126 markedly
      attenuated OVA-induced tyrosine phosphorylation of ERK1/2. Taken together, our
      findings implicate that inhibition of ERK signaling pathway may have therapeutic
      potential for the treatment of allergic airway inflammation.

PMID- 15153528
TI  - Intracellular and cell surface localization of a complex between alphaMbeta2
      integrin and promatrix metalloproteinase-9 progelatinase in neutrophils.
AB  - We have recently demonstrated that promatrix metalloproteinases (proMMPs),
      particularly proMMP-9, are potent ligands of the leukocyte beta(2) integrins. We
      studied here the complex formation between proMMP-9 and alpha(M)beta(2), the
      major MMP and integrin of neutrophils. On resting neutrophils, the proMMP
      9/alpha(M)beta(2) complex was primarily detected in intracellular granules, but
      after cellular activation it became localized to the cell surface, as
      demonstrated by immunoprecipitation and double immunofluorescence. Further
      indication of the complex formation was that neutrophils and alpha(M)beta(2)
      transfected L cells, but not the wild-type L cells or leukocyte adhesion
      deficiency cells, bound to immobilized proMMP-9 or its recombinant catalytic
      domain in a beta(2) integrin-dependent manner. Peptides that bound to the
      alpha(M) integrin-I domain and inhibited its complex formation with proMMP-9
      prevented neutrophil migration in a transendothelial assay in vitro and in a
      thioglycolate-elicited peritonitis in vivo. These results suggest that the
      translocating proMMP-9/alpha(M)beta(2) complex may be part of the cell surface
      machinery guiding neutrophil migration.

PMID- 15153529
TI  - Iron chelator triggers inflammatory signals in human intestinal epithelial cells:
      involvement of p38 and extracellular signal-regulated kinase signaling pathways.
AB  - Competition for cellular iron (Fe) is a vital component of the interaction
      between host and pathogen. Most bacteria have an obligate requirement for Fe to
      sustain infection, growth, and survival in host. To obtain iron required for
      growth, many bacteria secrete iron chelators (siderophores). This study was
      undertaken to test whether a bacterial siderophore, deferoxamine (DFO), could
      trigger inflammatory signals in human intestinal epithelial cells as a single
      stimulus. Incubation of human intestinal epithelial HT-29 cells with DFO
      increased the expression of IL-8 mRNA, as well as the release of IL-8 protein.
      The signal transduction study revealed that both p38 and extracellular signal
      regulated kinase-1/2 were significantly activated in response to DFO.
      Accordingly, the selective inhibitors for both kinases, either alone or in
      combination, completely abolished DFO-induced IL-8 secretion, indicating an
      importance of mitogen-activated protein kinases pathway. These proinflammatory
      effects of DFO were, in large part, mediated by activation of Na(+)/H(+)
      exchangers, because selective blockade of Na(+)/H(+) exchangers prevented the DFO
      induced IL-8 production. Interestingly, however, DFO neither induced NF-kappaB
      activation by itself nor affected IL-1beta- or TNF-alpha-mediated NF-kappaB
      activation, suggesting a NF-kappaB-independent mechanism in DFO-induced IL-8
      production. Global gene expression profiling revealed that DFO significantly up
      regulates inflammation-related genes including proinflammatory genes, and that
      many of those genes are down-modulated by the selective mitogen-activated protein
      kinase inhibitors. Collectively, these results demonstrate that, in addition to
      bacterial products or cell wall components, direct chelation of host Fe by
      infected bacteria may also contribute to the evocation of host inflammatory
      responses.

PMID- 15153530
TI  - Humanin, a newly identified neuroprotective factor, uses the G protein-coupled
      formylpeptide receptor-like-1 as a functional receptor.
AB  - Alzheimer's disease (AD) is characterized by overproduction of beta amyloid
      peptides in the brain with progressive loss of neuronal cells. The 42-aa form of
      the beta amyloid peptide (Abeta(42)) is implied as a major causative factor,
      because it is toxic to neurons and elicits inflammatory responses in the brain by
      activating microglial cells. Despite the overproduction of Abeta(42), AD brain
      tissue also generates protective factor(s) that may antagonize the
      neurodestructive effect of Abeta(42). Humanin is a gene cloned from an apparently
      normal region of an AD brain and encodes a 24-aa peptide. Both secreted and
      synthetic Humanin peptides protect neuronal cells from damage by Abeta(42), and
      the effect of Humanin may involve putative cellular receptor(s). To elucidate the
      molecular identity of such receptor(s), we examined the activity of synthetic
      Humanin on various cells and found that Humanin induced chemotaxis of mononuclear
      phagocytes by using a human G protein-coupled formylpeptide receptor-like-1
      (FPRL1) and its murine counterpart FPR2. Coincidentally, FPRL1 and FPR2 are also
      functional receptors used by Abeta(42) to chemoattract and activate phagocytic
      cells. Humanin reduced the aggregation and fibrillary formation by suppressing
      the effect of Abeta(42) on mononuclear phagocytes. In neuroblast cells, Humanin
      and Abeta(42) both activated FPRL1; however, only Abeta(42) caused apoptotic
      death of the cells, and its cytopathic effect was blocked by Humanin. We conclude
      that Humanin shares human FPRL1 and mouse FPR2 with Abeta(42) and suggest that
      Humanin may exert its neuroprotective effects by competitively inhibiting the
      access of FPRL1 to Abeta(42).

PMID- 15153531
TI  - Type I collagen is the autoantigen in experimental autoimmune anterior uveitis.
AB  - This study was undertaken to identify and characterize the Ag responsible for the
      induction of experimental autoimmune anterior uveitis (EAAU). Melanin-associated
      Ag isolated from bovine iris and ciliary body was digested with the proteolytic
      enzyme V8 protease to solubilize the proteins and the pathogenic protein was
      purified to homogeneity. Lewis rats were sensitized to various fractions and
      investigated for the development of anterior uveitis and an immune response to
      the purified Ag. The uveitogenic Ag had a mass of 22 kDa (SDS-PAGE) and an
      isoelectric point of 6.75. The N-terminal amino acid sequence of this protein
      demonstrated 100% homology with the bovine type I collagen alpha-2 chain starting
      from amino acid 385 and will be referred to as CI-alpha2 (22 kDa). Animals
      immunized with bovine CI-alpha2 (22 kDa) developed both cellular and humoral
      immunity to the Ag. They developed anterior uveitis only if the CI-alpha2 chain
      underwent proteolysis and if the bound carbohydrates were intact. EAAU induced by
      CI-alpha2 (22 kDa) can be adoptively transferred to naive syngenic rats by primed
      CD4(+) T cells. EAAU could not be induced by the adoptive transfer of sera
      obtained from animals immunized with CI-alpha2 (22 kDa). The alpha-1 and alpha-2
      chains (intact or proteolytically cleaved) of type I collagen from calfskin were
      not pathogenic. Although human anterior uveitis has been historically
      characterized as a collagen disease, this is first time collagen has been
      directly identified as the target autoantigen in uveitis.

PMID- 15153532
TI  - Platelet-activating factor receptor develops airway hyperresponsiveness
      independently of airway inflammation in a murine asthma model.
AB  - Lipid mediators play an important role in modulating inflammatory responses.
      Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with
      eosinophil chemotactic activity in vitro and in vivo. We show in this study that
      mice deficient in PAF receptor exhibited significantly reduced airway
      hyperresponsiveness to muscarinic cholinergic stimulation in an asthma model.
      However, PAF receptor-deficient mice developed an eosinophilic inflammatory
      response at a comparable level to that of wild-type mice. These results indicate
      an important role for PAF receptor, downstream of the eosinophilic inflammatory
      cascade, in regulating airway responsiveness after sensitization and aeroallergen
      challenge.

PMID- 15153533
TI  - Genomic and proteomic determinants of outcome in patients undergoing
      thoracoabdominal aortic aneurysm repair.
AB  - Thoracoabdominal aortic aneurysm repair, with its requisite intraoperative
      mesenteric ischemia-reperfusion, often results in the development of systemic
      inflammatory response syndrome, multiorgan dysfunction syndrome (MODS), and
      death. In the present study, an adverse clinical outcome following
      thoracoabdominal aortic aneurysm repair was identified by blood leukocyte genomic
      and plasma proteomic responses. Time-dependent changes in the expression of 146
      genes from blood leukocytes were observed (p < 0.001). Expression of 138 genes (p
      < 0.001) and the concentration of seven plasma proteins discriminated between
      patients who developed MODS and those who did not, and many of these differences
      were evident even before surgery. These findings suggest that changes in blood
      leukocyte gene expression and plasma protein concentrations can illuminate
      pathophysiological processes that are subsequently associated with the clinical
      sequelae of systemic inflammatory response syndrome and MODS. These changes in
      gene expression and plasma protein concentrations are often observed before
      surgery, consistent with either a genetic predisposition or pre-existing
      inflammatory state.

PMID- 15153534
TI  - CD56+ cells induce steroid resistance in B cells exposed to IL-15.
AB  - Interleukin-2 can induce steroid resistance in T cells. IL-15 shares biological
      activities with IL-2, as both cytokines use IL-2Rgamma for signal transduction.
      We therefore sought to determine whether IL-15 contributes to induction of PBMC
      corticosteroid resistance. Surprisingly, we found that incubation of
      unfractionated PBMC with IL-15 for 48 h resulted in the inhibition of
      glucocorticoid receptor (GCR) nuclear translocation in response to dexamethasone
      (DEX) treatment in CD19-positive B cells significantly greater than CD19-negative
      non-B cells (p < 0.01). However, pure B cells incubated with IL-15 responded
      normally with nuclear translocation of GCR in response to steroids, but failed to
      translocate GCR when they were grown in the presence of CD19(-) cells. Coculture
      of B cells with CD3(+) (T cells), CD14(+) (monocytes), or CD56(+) (NK and NKT
      cells) in the presence of IL-15 revealed that only CD56(+) cells contributed to
      the steroid insensitivity of B cells. IL-15 stimulation significantly increased
      production of IL-4 by CD56(+) cells (p < 0.02). Treatment of purified B cells
      with combination IL-15/IL-4 resulted in abrogation of glucocorticoid receptor
      nuclear translocation and the inability of DEX to suppress cytokine production by
      B cells. In the presence of IL-4-neutralizing Ab, when B cells were cocultured
      with CD56(+) cells and IL-15, the B cells were found to be steroid sensitive,
      i.e., DEX induced GCR nuclear translocation. This study demonstrates that B cells
      develop steroid resistance in the presence of CD56(+) cells after IL-15
      stimulation. Furthermore, IL-15 and IL-4 have the capacity to induce B cell
      insensitivity to steroids.

PMID- 15153535
TI  - BCL-6 mutations in pulmonary lymphoproliferative disorders: demonstration of an
      aberrant immunological reaction in HIV-related lymphoid interstitial pneumonia.
AB  - We used a PCR and sequence procedure to analyze the Ig V(H) gene and the
      mutations in the 5' regulatory regions of BCL-6 genes in pulmonary
      lymphoproliferative disorders (mucosa-associated lymphoid tissue (MALT) lymphoma,
      HIV-related, EBV-related, and virus-negative lymphocytic interstitial pneumonia
      (LIP)). Eight of 20 (40%) pulmonary MALT lymphoma and 10 of 20 LIP (5 of 5 (100%)
      HIV-related, 2 of 5 (40%) EBV-related, and 3 of 10 (30%) virus-negative LIP)
      cases showed BCL-6 gene mutations. Intraclonal heterogeneity of the BCL-6
      mutations was observed only in pulmonary MALT lymphoma cases whose Ig V(H) genes
      also showed intraclonal heterogeneity. Ongoing BCL-6 mutations might reflect re
      entry into a germinal center pathway to further mutations. BCL-6 mutations in
      pulmonary MALT lymphoma and HIV-negative LIP showed some features (high
      transition to transversion ratio, standard polarity, and RGYW/WRCY bias) of Ig
      V(H) gene hypermutation, leading to the view that pulmonary MALT lymphomas and
      HIV-negative LIP are under the influence of germinal center hypermutation
      mechanisms. Because BCL-6 mutations in HIV-related LIP cases did not demonstrate
      features of Ig V(H) gene hypermutation, immunological reactions in HIV-related
      LIP are the result of a process different from that found in HIV-negative
      pulmonary lymphoproliferative disorders.

PMID- 15153536
TI  - Phosphatidylinositol 3-kinase is involved in alpha2(I) collagen gene expression
      in normal and scleroderma fibroblasts.
AB  - TGF-beta is implicated in the pathogenesis of fibrotic disorders. It has been
      shown that Smad3 promotes the human alpha2(I) collagen (COL1A2) gene expression
      by TGF-beta1 in human dermal fibroblasts. Here, we investigated the role of
      phosphatidylinositol 3-kinase (PI3K) in the COL1A2 gene expression in normal and
      scleroderma fibroblasts. In normal fibroblasts, the PI3K inhibitor, LY294002,
      significantly decreased the basal and the TGF-beta1-induced increased stability
      of COL1A2 mRNA. The TGF-beta1-induced COL1A2 promoter activity, but not the basal
      activity, was significantly attenuated by LY294002 or the dominant negative
      mutant of p85 subunit of PI3K, while the constitutive active mutant of p110
      subunit of PI3K did not affect the basal or the TGF-beta1-induced COL1A2 promoter
      activity. LY294002 significantly decreased the phosphorylation of Smad3 induced
      by TGF-beta1. Furthermore, the transient overexpression of 2xFYVE, which induces
      the mislocalization of FYVE domain proteins, decreased the TGF-beta1-induced
      Smad3 phosphorylation to a similar extent to LY294002. In scleroderma
      fibroblasts, the blockade of PI3K significantly decreased the mRNA stability and
      the promoter activity of the COL1A2 gene. Furthermore, LY294002 and the transient
      overexpression of 2xFYVE completely diminished the constitutive phosphorylation
      of Smad3. These results indicate that 1) the basal activity of PI3K is necessary
      for the COL1A2 mRNA stabilization in normal and scleroderma fibroblasts, 2) there
      is an unidentified FYVE domain protein specifically interacting with Smad3, and
      3) the basal activity of PI3K and the FYVE domain protein are indispensable for
      the efficient TGF-beta/Smad3 signaling in normal fibroblasts and for the
      establishment of the constitutive activation of TGF-beta/Smad3 signaling in
      scleroderma fibroblasts.

PMID- 15153537
TI  - Stroma cell-derived factor 1alpha mediates desensitization of human neutrophil
      respiratory burst in synovial fluid from rheumatoid arthritic patients.
AB  - Classical chemoattractants such as fMLP or the complement factor C5a use G
      protein (Gi)-coupled receptors to stimulate both chemotaxis and production of
      reactive oxygen species (respiratory burst, RB) by polymorphonuclear leukocytes
      (PMN). The chemokine stroma cell-derived factor 1alpha (SDF1alpha) and its Gi
      coupled receptor, CXCR4, regulate leukocyte trafficking and recruitment to the
      synovial fluid of rheumatoid arthritic patients (RA-SF). However, the role of
      SDF1alpha in the RB is unknown and was studied in this work in vitro with healthy
      PMN in the absence and presence of RA-SF. In healthy PMN, SDF1alpha failed to
      stimulate the RB, even though the p38 mitogen-activated protein kinase was
      activated to a similar level as in fMLP-stimulated PMN. In contrast, the
      SDF1alpha-mediated calcium transients and activation of phosphatidylinositol 3
      kinase/Akt were partially deficient, while p44/42 mitogen-activated protein
      kinases were not activated. SDF1alpha actually desensitized weakly the fMLP
      mediated RB of healthy PMN. This cross-inhibitory effect was amplified in PMN
      treated with RA-SF, providing a protection against the exacerbation of RB induced
      by C5a or fMLP. This SDF1alpha beneficial effect, which was prevented by the
      CXCR4 antagonist AMD3100, was associated with impairment of C5a- and fMLP
      mediated early signaling events. Thus, although SDF1alpha promotes leukocyte
      emigration into rheumatoid synovium, our data suggest it cross-desensitizes the
      production of oxidant by primed PMN, a property that may be beneficial in the
      context of arthritis.

PMID- 15153538
TI  - Type 2 monocyte and microglia differentiation mediated by glatiramer acetate
      therapy in patients with multiple sclerosis.
AB  - Glatiramer acetate (GA) therapy of patients with multiple sclerosis (MS)
      represents a unique setting in which in vivo Th2 deviation of T cells is
      consistently observed and associated with clinical benefit in a human autoimmune
      disease. We postulated that APCs are important targets of GA therapy and
      demonstrate that treatment of MS patients with GA reciprocally regulates the IL
      10/IL-12 cytokine network of monocytes in vivo. We further show that Th1- or Th2
      polarized GA-reactive T cells isolated from untreated or treated MS patients
      mediate type 1 and 2 APC differentiation of human monocytes, based on their
      ability to efficiently induce subsequent Th1 and Th2 deviation of naive T cells,
      respectively. These observations are extended to human microglia, providing the
      first demonstration of type 2 differentiation of CNS-derived APCs. Finally, we
      confirm that the fundamental capacity of polarized T cells to reciprocally
      modulate APC function is not restricted to GA-reactive T cells, thereby defining
      a novel and dynamic positive feedback loop between human T cell and APC
      responses. In the context of MS, we propose that GA therapy results in the
      generation of type 2 APCs, contributing to Th2 deviation both in the periphery
      and in the CNS of MS patients. In addition to extending insights into the
      therapeutic mode of action of GA, our findings revisit the concept of bystander
      suppression and underscore the potential of APCs as attractive targets for
      therapeutic immune modulation.

PMID- 15153539
TI  - Topical glucocorticoid therapy directly induces up-regulation of functional CXCR4
      on primed T lymphocytes in the aqueous humor of patients with uveitis.
AB  - Overexpression of the constitutive chemokine receptor CXCR4 has been shown to
      contribute to the accumulation of leukocytes at sites of chronic inflammation.
      Glucocorticoids are widely used to treat inflammatory disorders such as uveitis
      to considerable effect, yet paradoxically have been reported to increase CXCR4
      expression in vitro. We show here that ocular lymphocytes isolated from patients
      with uveitis who had been treated with topical glucocorticoids expressed highly
      elevated levels of CXCR4. The up-regulation of CXCR4 could be reproduced in vitro
      by culture of CD4(+) T cells with aqueous humor (AqH), indicating a role for the
      ocular microenvironment rather than preferential recruitment of CXCR4(+) cells.
      Untreated uveitis and noninflammatory AqH up-regulated CXCR4 to a limited extent;
      this was dependent on TGF-beta2. However, the highest levels of CXCR4 both in
      vivo and in vitro were found in the glucocorticoid-treated patients.
      Glucocorticoids appeared to be directly responsible for the induction of CXCR4 in
      treated patients, as the glucocorticoid receptor antagonist RU38486 inhibited the
      in vitro up-regulation by AqH from these patients. Dexamethasone selectively up
      regulated CXCR4 in vitro, but not any of a wide range of other chemokine
      receptors. CXCL12, the ligand for CXCR4, was present in AqH under noninflammatory
      conditions, but the levels were low in untreated uveitis and undetectable in
      treated uveitis AqH. The importance of these results for the treatment of HIV
      patients with glucocorticoids is discussed as well as a role for glucocorticoid
      induced CXCR4 up-regulation and CXCL12 down-regulation in controlling the
      migration of lymphocyte populations, resulting in resolution of inflammation.

PMID- 15153540
TI  - Induction of human dendritic cell maturation using transfection with RNA encoding
      a dominant positive toll-like receptor 4.
AB  - Maturation of dendritic cells (DC) is critical for the induction of Ag-specific
      immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to
      Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in
      animal models. However, clinical use of LPS is limited due to potential toxicity.
      Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by
      stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed
      a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human
      DC with RNA encoding caTLR4 led to IL-12 and TNF-alpha secretion. Transfection
      with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of
      DC with caTLR4 RNA enhanced allostimulation of CD4(+) T cells. DC transfected
      with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to
      stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced
      the generation of MART-specific CTL. This CTL activity was superior to that seen
      when DC maturation was induced using either LPS or a standard mixture of
      cytokines (TNF-alpha, IL-6, IL-1beta, and PGE(2)). We conclude that transfection
      of DC with RNA encoding a functional signaling protein, such as caTLR4, may
      provide a new tool for studying TLR signaling in DC and may be a promising
      approach for the induction of DC maturation for tumor immunotherapy.

PMID- 15153541
TI  - T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are
      differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid
      derived mononuclear cells in multiple sclerosis.
AB  - T cell Ig- and mucin-domain-containing molecules (TIMs) comprise a recently
      described family of molecules expressed on T cells. TIM-3 has been shown to be
      expressed on murine Th1 cell clones and has been implicated in the pathogenesis
      of Th1-driven experimental autoimmune encephalomyelitis. In contrast, association
      of TIM-1 polymorphisms to Th2-related airway hyperreactivity has been suggested
      in mice. The TIM molecules have not been investigated in human Th1- or Th2
      mediated diseases. Using real-time (TaqMan) RT-PCR, we show that human Th1 lines
      expressed higher TIM-3 mRNA levels, while Th2 lines demonstrated a higher
      expression of TIM-1. Analysis of cerebrospinal fluid mononuclear cells obtained
      from patients with multiple sclerosis revealed significantly higher mRNA
      expression of TIM-1 compared with controls. Moreover, higher TIM-1 expression was
      associated with clinical remissions and low expression of IFN-gamma mRNA in
      cerebrospinal fluid mononuclear cells. In contrast, expression of TIM-3
      correlated well with high expression of IFN-gamma and TNF-alpha. These data imply
      the differential expression of human TIM molecules by Th1 and Th2 cells and may
      suggest their differential involvement in different phases of a human autoimmune
      disease.

PMID- 15153542
TI  - Inhibition of B cell death causes the development of an IgA nephropathy in (New
      Zealand white x C57BL/6)F(1)-bcl-2 transgenic mice.
AB  - Little is known about the pathogenic mechanisms of IgA nephropathy, despite being
      the most prevalent form of glomerulonephritis in humans. We report in this study
      that in (New Zealand White (NZW) x C57BL/6)F(1) mice predisposed to autoimmune
      diseases, the expression of a human bcl-2 (hbcl-2) transgene in B cells promotes
      a CD4-dependent lupus-like syndrome characterized by IgG and IgA
      hypergammaglobulinemia, autoantibody production, and the development of a fatal
      glomerulonephritis. Histopathological analysis of glomerular lesions reveals that
      the glomerulonephritis observed in these animals resembles that of human IgA
      nephropathy. The overexpression of Bcl-2 in B cells selectively enhances systemic
      IgA immune responses to T-dependent Ags. Significantly, serum IgA purified from
      (NZW x C57BL/6)F(1)-hbcl-2 transgenic mice, but not from nontransgenic
      littermates, shows reduced levels of galactosylation and sialylation and an
      increased ability to deposit in the glomeruli, as observed in human patients with
      IgA nephropathy. Our results indicate that defects in the regulation of B
      lymphocyte survival associated with aberrant IgA glycosylation may be critically
      involved in the pathogenesis of IgA nephropathy, and that (NZW x C57BL/6)F(1)
      hbcl-2 Tg mice provide a new experimental model for this form of
      glomerulonephritis.

PMID- 15153543
TI  - A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif
      bearing FcgammaRIIb alters receptor expression and associates with autoimmunity.
      I. Regulatory FCGR2B polymorphisms and their association with systemic lupus
      erythematosus.
AB  - FcgammaRIIb, the immunoreceptor tyrosine-based inhibitory motif-containing
      receptor for IgG (Mendelian Inheritance in Man no. 604590), plays an important
      role in maintaining the homeostasis of immune responses. We have identified 10
      novel single-nucleotide polymorphisms in the promoter region of human FCGR2B gene
      and characterized two functionally distinct haplotypes in its proximal promoter.
      In luciferase reporter assays, the less frequent promoter haplotype leads to
      increased expression of the reporter gene in both B lymphoid and myeloid cell
      lines under constitutive and stimulated conditions. Four independent genome-wide
      scans support linkage of the human FcgammaR region to the systemic lupus
      erythematosus (SLE; Online Mendelian Inheritance in Man no. 152700) phenotype.
      Our case-control study in 600 Caucasians indicates a significant association of
      the less frequent FCGR2B promoter haplotype with the SLE phenotype (odds ratio =
      1.65; p = 0.0054). The FCGR2B haplotype has no linkage disequilibrium with
      previously identified FCGR2A and FCGR3A polymorphisms, and after adjustment for
      FCGR2A and FCGR3A, FCGR2B showed a persistent association with SLE (odds ratio =
      1.72; p = 0.0083). These results suggest that an expression variant of FCGR2B is
      a risk factor for human lupus and implicate FCGR2B in disease pathogenesis.

PMID- 15153544
TI  - A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif
      bearing FcgammaRIIb alters receptor expression and associates with autoimmunity.
      II. Differential binding of GATA4 and Yin-Yang1 transcription factors and
      correlated receptor expression and function.
AB  - The immunoreceptor tyrosine-based inhibitory motif-containing FcgammaRIIb
      modulates immune function on multiple cell types including B cells,
      monocytes/macrophages, and dendritic cells. The promoter for the human FCGR2B is
      polymorphic, and the less frequent 2B.4 promoter haplotype is associated with the
      autoimmune phenotype of systemic lupus erythematosus. In the present study, we
      demonstrate that the 2B.4 promoter haplotype of FCGR2B has increased binding
      capacity for GATA4 and Yin-Yang1 (YY1) transcription factors in both B
      lymphocytes and monocytes, and that overexpression of GATA4 or YY1 enhances the
      FCGR2B promoter activity. The 2B.4 haplotype leads to elevated expression of the
      endogenous receptor in heterozygous donors by approximately 1.5-fold as assessed
      on EBV-transformed cells, primary B lymphocytes, and CD14(+) monocytes. This
      increased expression accentuates the inhibitory effect of FcgammaRIIb on B cell
      Ag receptor signaling, measured by Ca(2+) influx and cell viability in B cells.
      Our results indicate that transcription factors GATA4 and YY1 are involved in the
      regulation of FcgammaRIIb expression, and that the expression variants of
      FcgammaRIIb lead to altered cell signaling, which may contribute to autoimmune
      pathogenesis in humans.

PMID- 15153545
TI  - Adenovirus CD40 ligand gene therapy counteracts immune escape mechanisms in the
      tumor Microenvironment.
AB  - Tumors exhibit immune escape properties that promote their survival. These
      properties include modulation of Ag presentation, secretion of immunosuppressive
      factors, resistance to apoptosis, and induction of immune deviation, e.g.,
      shifting from Th1- to Th2-type responses. These escape mechanisms have proven to
      hamper several immunotherapeutic strategies, and efforts need to be taken to
      revert this situation. We have studied the immunological effects of introducing
      CD40 ligand (CD40L), a potent dendritic cell activation molecule, into the tumor
      micromilieu by adenoviral gene transfer. For this purpose, a murine bladder
      cancer model (MB49) was used in C57BL/6 mice. The MB49 cells are known to induce
      IL-10 in the tumor environment. IL-10 potently inhibits the maturation of
      dendritic cells and thereby also the activation of CTLs. In this paper we show
      that CD40L immunogene therapy suppresses IL-10 and TGF-beta production (2-fold
      decrease) and induces a typical Th1-type response in the tumor area (200-fold
      increase in IL-12 production). The antitumor responses obtained were MB49 cell
      specific, and the cytotoxicity of the stimulated CD8(+) cells could be blocked by
      IL-10. Adenovirus CD40L therapy was capable of regressing small tumors (five of
      six animals were tumor free) and inhibiting the progression of larger tumors even
      in the presence of other escape mechanisms, such as apoptosis resistance.
      Furthermore, CD40L-transduced MB49 cells promoted the maturation of dendritic
      cells (2-fold increase in IL-12) independently of IL-10. Our results argue for
      using adenovirus CD40L gene transfer, alone or in combination with other
      modalities, for the treatment of Th2-dominated tumors.

PMID- 15153546
TI  - Identification of an SSX-2 epitope presented by dendritic cells to circulating
      autologous CD4+ T cells.
AB  - Accumulating evidence supports the requirement for both tumor-specific CD8(+) and
      CD4(+) T cell responses for efficient tumor rejection to occur. Because of its
      expression in different tumor types, the cancer/testis Ag encoded by the synovial
      sarcoma X breakpoint 2 (SSX-2) gene is among the most relevant candidates for the
      development of generic cancer vaccines. The immunogenicity of SSX-2 has been
      previously corroborated by detection of specific humoral and CD8(+) T cell
      responses in cancer patients. In this study we report identification of the first
      CD4(+) T cell epitope encoded by SSX-2. The identified epitope mapped to the 19
      34 region of the protein and was recognized by CD4(+) T cells from an Ag
      expressing melanoma patient in association with HLA-DPB1*0101. The absence of
      detectable response in healthy donors and other patients suggests that SSX-2
      specific CD4(+) T cells in the responder patient had been previously expanded in
      vivo in response to the autologous tumor. The epitope did not appear to be
      presented on the surface of tumor cells at levels sufficient to allow direct
      recognition. In contrast, it was efficiently presented by autologous dendritic
      cells, supporting the concept that processing by professional APC is the main
      pathway through which the CD4(+) T cell immunoresponse to tumor Ags occurs in
      vivo.

PMID- 15153547
TI  - Antiretroviral drug resistance mutations sustain or enhance CTL recognition of
      common HIV-1 Pol epitopes.
AB  - Antiretroviral drug resistance and escape from CTL are major obstacles to
      effective control of HIV replication. To investigate the possibility of combining
      drug and immune-based selective pressures against HIV, we studied the effects of
      antiretroviral drug resistance mutations on CTL recognition of five HIV-1 Pol
      epitopes presented by common HLA molecules. We found that these common drug
      resistance mutations sustain or even enhance the antigenicity and immunogenicity
      of HIV-1 Pol CTL epitopes. Variable patterns of cross-reactive and selective
      recognition of wild-type and corresponding variant epitopes demonstrate a
      relatively diverse population of CD8(+) T cells reactive against these epitopes.
      Variant peptides with multiple drug resistance mutations still sustained CTL
      recognition, and some HIV-infected individuals demonstrated strong CD8(+) T cell
      responses against multiple CTL epitopes incorporating drug resistance mutations.
      Selective reactivity against variant peptides with drug resistance mutations
      reflected ongoing or previous exposure to the indicated drug, but was not
      dependent upon the predominance of the mutated sequence in endogenous virus. The
      frequency and diversity of CTL reactivity against the variant peptides
      incorporating drug resistance mutations and the ability of these peptides to
      activate and expand CTL precursors in vitro indicate a significant functional
      interface between the immune system and antiretroviral therapy. Thus, drug
      resistant variants of HIV are susceptible to immune selective pressure that could
      be applied to combat transmission or emergence of antiretroviral drug-resistant
      HIV strains and to enhance the immune response against HIV.

PMID- 15153548
TI  - Renal epithelial traffic jams and one-way streets.

PMID- 15153549
TI  - Signaling at the slit diaphragm.

PMID- 15153550
TI  - Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin.
AB  - Hyperphosphatemia is thought to underlie medial vascular calcification in
      advanced renal failure, but calcification can occur in other conditions in the
      absence of hyperphosphatemia, indicating that additional factors are important.
      To identify these factors, a model of medial calcification in rat aorta in vitro
      was developed. Aortic rings from rats were incubated in serum-free medium for 9
      d, and calcification was measured as incorporation of (45)Ca and confirmed by
      histology and x-ray diffraction. No calcification occurred in normal vessels
      despite elevated free Ca(2+) and PO(4)(3-) concentrations of 1.8 mM and 3.8 mM,
      respectively, but mechanical injury resulted in extensive calcification in the
      media. Co-incubation studies revealed that normal aortas produced a soluble
      inhibitor of calcification in injured vessels that was destroyed by alkaline
      phosphatase. Culture of normal aortas with alkaline phosphatase resulted in
      calcification of the elastic lamina identified as hydroxyapatite by x-ray
      diffraction. This effect of alkaline phosphatase was not due to dephosphorylation
      of osteopontin (OPN), and calcification was not increased in aortas from OPN
      deficient mice. The inhibitor was identified as pyrophosphate on the basis of the
      calcification induced in aortas cultured with inorganic pyrophosphatase, the
      inhibition of calcification in injured aortas by pyrophosphate, and the
      production of inhibitory levels of pyrophosphate by normal aortas. No
      calcification occurred under any conditions at a normal PO(4)(3-) concentration.
      It is concluded that elevated concentrations of Ca(2+) and PO(4)(3-) are not
      sufficient for medial vascular calcification because of inhibition by
      pyrophosphate. Alkaline phosphatase can promote calcification by hydrolyzing
      pyrophosphate, but OPN is not an endogenous inhibitor of calcification in rat
      aorta.

PMID- 15153551
TI  - Hepatocyte growth factor antagonizes the profibrotic action of TGF-beta1 in
      mesangial cells by stabilizing Smad transcriptional corepressor TGIF.
AB  - Mesangial cell activation is a predominant pathologic feature of diabetic
      nephropathy that precedes the accumulation of extracellular matrix leading to
      glomerulosclerosis. For understanding the potential mechanism by which hepatocyte
      growth factor (HGF) ameliorates diabetic nephropathy, the effects of HGF on
      mesangial cell activation induced by TGF-beta1 were investigated. Western blot
      analysis and immunostaining revealed that HGF suppressed alpha-smooth muscle
      actin expression induced by TGF-beta1 in cultured rat and human mesangial cells.
      HGF also inhibited TGF-beta1-mediated fibronectin and type I collagen expression.
      Such action of HGF was dependent on the activation of extracellular signal
      regulated kinase-1 and -2 but not on Akt and p38 mitogen-activated protein
      kinase. HGF did not affect TGF-beta1-mediated Smad2 phosphorylation and its
      nuclear translocation. However, it rapidly upregulated Smad transcriptional
      corepressor TG-interacting factor (TGIF) abundance in mesangial cells, which was
      primarily mediated by stabilizing its protein from degradation. Ectopic
      expression of TGIF markedly suppressed Smad-mediated activation of TGF-beta1
      responsive promoter activity and completely blocked TGF-beta1-induced alpha
      smooth muscle actin expression. In vivo, TGIF expression was dramatically
      downregulated in the glomeruli of diabetic kidneys, and delivery of exogenous HGF
      induced TGIF expression. These results suggest that HGF specifically antagonizes
      the profibrotic action of TGF-beta1 in mesangial cells by stabilizing Smad
      transcriptional corepressor TGIF.

PMID- 15153552
TI  - Role of nitric oxide in the renal hemodynamic response to unilateral nephrectomy.
AB  - Reduction of renal mass by unilateral nephrectomy results in an immediate
      increase in renal blood flow (RBF) to the remnant kidney, followed by
      compensatory renal hypertrophy. Whether the increase in RBF after unilateral
      nephrectomy is mediated by nitric oxide (NO) was tested. It was found that
      immediately after nephrectomy, blood flow to the remaining kidney increased by 8%
      (P < 0.01), and inhibition of NO synthesis with Nomega-nitro-L-arginine methyl
      ester (L-NAME) blocked the increase in RBF. In addition, 2 d after nephrectomy,
      there was a 49% increase in RBF (corrected per gram of kidney weight), a 25%
      increase at 7 and 14 d, and a 16% increase after 28 d. Acute inhibition of NO
      synthesis with L-NAME in uninephrectomized rats caused a greater decrease in RBF
      on days 2 and 7 compared with controls, whereas by 14 and 28 d, the response to L
      NAME was similar to controls. Urinary excretion of cyclic guanosine
      monophosphate, a marker for renal NO production, increased 2.5-fold by 2 d after
      uninephrectomy (P < 0.005) and remained at this level through 28 d. Pretreating
      rats chronically with a subpressor dose of L-NAME beginning 2 d before
      nephrectomy blocked the increase in RBF seen at 2 and 7 d and retarded the renal
      hypertrophy that should have developed by 7 d. It is concluded that after
      unilateral nephrectomy, immediate and sustained increases in RBF are mediated at
      least in part by NO. The hypertrophic response to unilateral nephrectomy may be
      partially initiated by the signal of hemodynamic changes.

PMID- 15153553
TI  - Differential expression of calcineurin A isoforms in the diabetic kidney.
AB  - Calcineurin is an important signaling molecule in mesangial cells in vitro and is
      involved in some manifestations of diabetic nephropathy in vivo. However,
      calcineurin acts in a cell-specific and tissue-specific manner in the kidney, and
      mechanisms of specificity are unknown. Three closely related isoforms of the
      calcineurin A (CnA) subunit are expressed in a tissue-specific manner. This study
      was undertaken to determine if specificity of calcineurin action is linked to
      regulation of CnA isoforms in the diabetic kidney. After induction of diabetes
      with streptozotocin, expression of all three CnA isoforms rapidly increased,
      primarily in the thick ascending limb of Henle (TAL). After prolonged diabetes,
      increase specifically of the alpha isoform was observed in collecting ducts (CD)
      and in endothelial cells of glomeruli. Aquaporin 2 (AQP2), a putative substrate
      of calcineurin phosphatase in the kidney, is also involved in diabetic
      nephropathy. Co-localization of CnA isoforms with AQP2 revealed that CnA-alpha is
      the predominant isoform that associates with AQP2 in the diabetic kidney.
      Furthermore, inhibition of calcineurin with cyclosporin A (CsA) alters AQP2
      localization and phosphorylation in principal cells of CD. Alterations in
      subcellular localization of AQP2 were parallel with CnA-alpha. Similarly, CsA
      treatment results in a further increase in urine output compared with diabetes
      alone, suggesting a functional consequence of inhibiting calcineurin-mediated
      regulation of AQP2. In conclusion, all three isoforms of CnA are upregulated in
      the diabetic kidney. Increased expression of CnA-alpha, in particular, is
      observed in glomeruli and CD and participates in regulation of AQP2 expression,
      phosphorylation, and function.

PMID- 15153554
TI  - Reduction in connective tissue growth factor by antisense treatment ameliorates
      renal tubulointerstitial fibrosis.
AB  - Connective tissue growth factor (CTGF/CCN2) is one of the candidate factors
      mediating fibrogenic activity of TGF-beta. It was shown previously that the
      blockade of CTGF by antisense oligonucleotide (ODN) inhibits TGF-beta-induced
      production of fibronectin and type I collagen in cultured renal fibroblasts. The
      in vivo contribution of CTGF in renal interstitial fibrosis, however, remains to
      be clarified. With the use of a hydrodynamics-based gene transfer technique, the
      effects of CTGF antisense ODN are investigated in rat kidneys with unilateral
      ureteral obstruction (UUO). FITC-labeled ODN injection via the renal vein showed
      that the ODN was specifically introduced into the interstitium. At day 7 after
      UUO, the gene expression of CTGF, fibronectin, fibronectin ED-A, and alpha1(I)
      collagen in untreated or control ODN-treated obstructed kidneys was prominently
      upregulated. CTGF antisense ODN treatment, by contrast, markedly attenuated the
      induction of CTGF, fibronectin, fibronectin ED-A, and alpha1(I) collagen genes,
      whereas TGF-beta gene upregulation was not affected. The antisense treatment also
      reduced interstitial deposition of CTGF, fibronectin ED-A, and type I collagen
      and the interstitial fibrotic areas. The number of myofibroblasts determined by
      the expression of alpha-smooth muscle actin was significantly decreased as well.
      Proliferation of tubular and interstitial cells was not altered with the
      treatment. These findings indicate that CTGF expression in the interstitium plays
      a crucial role in the progression of interstitial fibrosis but not in the
      proliferation of tubular and interstitial cells during UUO. CTGF may become a
      potential therapeutic target against tubulointerstitial fibrosis.

PMID- 15153555
TI  - Inactivation of endoplasmic reticulum bound Ca2+-independent phospholipase A2 in
      renal cells during oxidative stress.
AB  - The purpose of this study was to determine the actions of oxidants on endoplasmic
      reticulum bound Ca(2+)-independent phospholipase A(2) (ER-iPLA(2)) and
      phospholipids in renal cells. Exposure of renal proximal tubule cells (RPTC) to
      the oxidants tert-butyl hydroperoxide (TBHP), cumene hydroperoxide, and cisplatin
      resulted in time- and concentration-dependent decreases in the activity of ER
      iPLA(2). TBHP-induced ER-iPLA(2) inactivation was reversed by the addition of
      dithiothreitol to microsomes isolated from treated RPTC. TBHP also directly
      inactivated ER-iPLA(2) in microsomes isolated from untreated RPTC. Similar to
      RPTC, dithiothreitol prevented TBHP-induced ER-iPLA(2) inactivation in microsomes
      as did the reactive oxygen scavengers butylated hydroxytoluene and N,N'-diphenyl
      p-phenylenediamine and the iron chelator deferoxamine. Electron paramagnetic
      resonance spin trapping demonstrated that TBHP initiated a carbon-centered
      radical after 1 min of exposure in microsomes, preceding ER-iPLA(2) inactivation,
      and further studies suggested that the formation of the carbon-centered radical
      species occurred after or in concert with the formation of oxygen-centered
      radicals. Phospholipid content was determined after TBHP exposure in the presence
      and absence of the ER-iPLA(2) inhibitor bromoenol lactone. Treatment of RPTC with
      TBHP resulted in 35% decreases in (16:0, 20:4)-phosphatidylethanolamine (PtdEtn),
      (18:0, 18:1)-plasmenylethanolamine (PlsEtn), a 30% decrease in (16:0, 18:3)
      phosphatidylcholine (PtdCho), and a 25% decrease in (16:0, 20:4)
      phosphatidylcholine (PtdCho). In contrast, treatment of RPTC with bromoenol
      lactone before TBHP exposure decreased the content of 11 phospholipids,
      decreasing a majority of PlsEtn phospholipids 60%, and 4 of the 8 PlsCho
      phospholipids 40%, while PtdCho and PtdEtn were marginally affected compared with
      TBHP. These data demonstrate that ER-iPLA(2) is inactivated by oxidants, that the
      mechanism of inactivation involves the oxidation of ER-iPLA(2) sulfhydryl groups,
      and that ER-iPLA(2) inhibition increases oxidant-induced RPTC phospholipid loss.

PMID- 15153556
TI  - Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2
      receptor.
AB  - Although both the renin angiotensin system (RAS) and the paired homeobox 2 gene
      (Pax-2) seem critically important in renal organogenesis, whether and how they
      might interact has not been addressed. The present study asked whether a link
      between the RAS and Pax-2 exists in fetal renal cells, speculating that such an
      interaction, if present, might influence renal development. Embryonic kidney
      explants and embryonic renal cells (mouse late embryonic mesenchymal epithelial
      cells [MK4] and mouse early embryonic mesenchymal fibroblasts [MK3]) were used.
      Pax-2 protein and Pax-2 mRNA were detected by immunofluorescence, Western blot,
      reverse transcription-PCR, and real-time PCR. Angiotensin II (AngII) upregulated
      Pax-2 protein and Pax-2 mRNA expression via the AngII type 2 (AT(2)) receptor in
      MK4 but not in MK3 cells. The stimulatory effect of AngII on Pax-2 gene
      expression could be blocked by PD123319 (AT(2) inhibitor), AG 490 (a specific
      Janus kinase 2 inhibitor), and genistein (a tyrosine kinase inhibitor) but not by
      losartan (AT(1) inhibitor), SB203580 (specific p38 mitogen-activated protein
      kinase inhibitor), PD98059 (specific MEK inhibitor), SP600125 (JNK inhibitor),
      and diphenyleneiodonium chloride (an NADPH oxidase inhibitor). Moreover,
      embryonic kidney explants in culture confirmed that AngII upregulates Pax-2 gene
      expression via the AT(2) receptor. These studies demonstrate that the stimulatory
      effect of AngII on Pax-2 gene expression is mediated, at least in part, via the
      Janus kinase 2/signal transducers and activators of transcription signaling
      transduction pathway, suggesting that RAS and Pax-2 interactions may be important
      in renal development.

PMID- 15153557
TI  - Mouse model of X-linked Alport syndrome.
AB  - X-linked Alport syndrome (XLAS) is a progressive disorder of basement membranes
      caused by mutations in the COL4A5 gene, encoding the alpha5 chain of type IV
      collagen. A mouse model of this disorder was generated by targeting a human
      nonsense mutation, G5X, to the mouse Col4a5 gene. As predicted for a nonsense
      mutation, hemizygous mutant male mice are null and heterozygous carrier female
      mice are mosaic for alpha5(IV) chain expression. Mutant male mice and carrier
      female mice are viable through reproductive age and fertile. Mutant male mice
      died spontaneously at 6 to 34 wk of age, and carrier female mice died at 8 to 45
      wk of age, manifesting proteinuria, azotemia, and progressive and manifold
      histologic abnormalities of the kidney glomerulus and tubulointerstitium.
      Ultrastructural abnormalities of the glomerular basement membrane, including
      lamellation and splitting, were characteristic of human XLAS. The mouse model
      described here recapitulates essential clinical and pathologic findings of human
      XLAS. With alpha5(IV) expression reflecting X-inactivation patterns, it will be
      especially useful in studying determinants of disease variability in the carrier
      state.

PMID- 15153558
TI  - Angiotensin II type 1 receptor overexpression in podocytes induces
      glomerulosclerosis in transgenic rats.
AB  - Angiotensin II (AngII) is a critical determinant of glomerular function involving
      both hemodynamic and pressure-independent effects that are insufficiently
      understood. A novel transgenic rat (TGR) model with overexpression of the human
      AngII type 1 receptor (hAT1) in podocytes was developed to study the consequences
      of an increased AT1 signaling on the structure and function of the glomerular
      filter. Use of the nephrin promoter to target the podocytes resulted in an
      expression of the hAT1 at a level roughly two times higher than the endogenous
      AT1 throughout life. All male TGR developed significant albuminuria starting at 8
      to 15 wk of age; systolic BP was not elevated. More or less concurrently,
      structural changes at the glomerulus were encountered, starting with ubiquitous
      formation of pseudocysts at podocytes, followed by foot process effacement and
      local detachments. This damage progressed to nephron loss via the well known
      pathway typical for classic focal segmental glomerulosclerosis. The structural
      changes significantly correlated with age (r(2) = 0.76) and urinary albumin
      excretion (r(2) = 0.70). The data provide direct evidence that increased AT1
      signaling in podocytes leads to protein leakage and structural podocyte damage
      progressing to focal segmental glomerulosclerosis.

PMID- 15153559
TI  - Anandamide decreases glomerular filtration rate through predominant vasodilation
      of efferent arterioles in rat kidneys.
AB  - For determining the effects of anandamide (ANA) on renal hemodynamics and
      microcirculation, a clearance study was performed in Sprague-Dawley rats that
      received injections of ANA in doses of 15, 150, and 1500 pmol/kg. At doses up to
      150 pmol/g, ANA significantly decreased GFR and increased renal blood flow (RBF)
      without affecting mean arterial pressure (MAP). In the presence of the
      cannabinoid type 1 (CB1) receptor antagonist AM251, only the 15-pmol/kg dose
      significantly increased GFR and RBF without altering MAP, with higher doses
      having no effect on GFR, RBF, or MAP. By contrast, AM281, which antagonizes
      cannabinoid receptors nonselectively, inhibited the GFR, RBF, and MAP responses
      to ANA. The arteriolar responses to ANA were also assessed in vitro by the blood
      perfused juxtamedullary nephron technique. Higher doses of ANA significantly
      increased the diameter of both afferent and efferent arterioles, whereas lower
      doses elicited predominant efferent arteriolar dilation. AM251 attenuated the
      afferent arteriolar response to ANA and inhibited the efferent arteriolar
      response to ANA, whereas AM281 inhibited the responses in both arterioles. The
      CB1 receptor mRNA was expressed in afferent arterioles, and immunohistochemical
      staining demonstrated the presence of CB1 receptors in both afferent and efferent
      arterioles. These results suggest that ANA causes afferent arteriolar dilation
      via both CB1 and non-CB1 receptors and greater efferent arteriolar dilation via
      CB1 receptors, resulting in a decreased GFR and an increased RBF without
      affecting MAP.

PMID- 15153560
TI  - Increased expression of adhesion molecules in uremic atherosclerosis in
      apolipoprotein-E-deficient mice.
AB  - Chronic renal failure markedly accelerates atherosclerosis in apolipoprotein-E
      deficient mice, but the mechanism is unknown. The recruitment of inflammatory
      cells in the arterial wall by vascular adhesion molecules plays a key role in the
      formation of classical atherosclerosis. This study examines whether the
      expression of vascular adhesion molecules is increased in uremic atherosclerosis.
      Uremia was induced by 5/6 nephrectomy; control mice were sham-operated. After 2
      wk of uremia, no lesion formation could be demonstrated in uremic or control
      mice. After 12 wk, aortas from uremic mice had a 9.8-fold increase of the aortic
      plaque area fraction compared with control mice (P < 0.0001). The aortic
      expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in uremic mice was
      215 +/- 31% (P < 0.05) and 243 +/- 55% (P < 0.05) of that in controls after 2 and
      12 wk, respectively (n = 9 x 4). In contrast, aortic expression of vascular cell
      adhesion molecule-1 (VCAM-1) mRNA in uremic mice was unchanged after 2 wk but
      increased to 237 +/- 40% (P < 0.01) of that in control mice after 12 wk. On
      immunohistochemistry of aortas from uremic mice, ICAM-1 was predominantly present
      in endothelial cells both in nonlesioned and lesioned aortas, whereas VCAM-1 was
      predominantly present in the medial smooth muscle cell layer in lesioned aortas.
      The plasma concentration of soluble ICAM-1 (sICAM-1) (but not of sVCAM-1) was
      slightly elevated after 2 wk of uremia. In contrast, both sICAM-1 and sVCAM-1
      plasma concentrations were markedly higher in uremic than control mice after 12
      wk. These results suggest that uremic atherosclerosis is preceded by an
      upregulation of ICAM-1 expression in arterial endothelium and that formation of
      early uremic lesions is accompanied by upregulation of VCAM-1 expression in the
      medial smooth muscle cell layer.

PMID- 15153562
TI  - Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the
      inflammatory response in unilateral ureteral obstruction.
AB  - Inflammatory cell infiltration plays a key role in the onset and progression of
      renal injury. The NF-kappaB participates in the inflammatory response, regulating
      many proinflammatory genes. Angiotensin II (Ang II), via AT(1) and AT(2)
      receptors, activates NF-kappaB. Although the contribution of Ang II to kidney
      damage progression is already established, the receptor subtype involved in the
      inflammatory cell recruitment is not clear. For investigating this issue, the
      unilateral ureteral obstruction (UUO) model was used in mice, blocking Ang II
      production/receptors and NF-kappaB pathway. Two days after UUO, obstructed
      kidneys of wild-type mice presented a marked interstitial inflammatory cell
      infiltration and increased NF-kappaB activity. Treatment with AT(1) or AT(2)
      antagonists partially decreased NF-kappaB activation, whereas only the AT(2)
      blockade diminished monocyte infiltration. Obstructed kidneys of AT(1)-knockout
      mice showed interstitial monocyte infiltration and NF-kappaB activation; both
      processes were abolished by an AT(2) antagonist, suggesting AT(2)/NF-kappaB
      involvement in monocyte recruitment. In wild-type mice, only angiotensin
      converting enzyme inhibition or combined therapy with AT(1) plus AT(2)
      antagonists blocked monocyte infiltration, NF-kappaB activation, and upregulation
      of NF-kappaB-related proinflammatory genes. Therefore, AT(1) and AT(2) blockade
      is necessary to arrest completely the inflammatory process. Treatment with two
      different NF-kappaB inhibitors, pirrolidin-dithiocarbamate and parthenolide,
      diminished monocyte infiltration and gene overexpression. These data show that
      Ang II, via AT(1) and AT(2) receptors and NF-kappaB pathway, participates in the
      regulation of renal monocyte recruitment and may provide a rationale to
      investigate further the role of AT(2) in human kidney diseases.

PMID- 15153561
TI  - Late onset of treatment with a chemokine receptor CCR1 antagonist prevents
      progression of lupus nephritis in MRL-Fas(lpr) mice.
AB  - Slowly progressive renal injury is the major cause for ESRD. The model of
      progressive immune complex glomerulonephritis in autoimmune MRL(lpr/lpr) mice was
      used to evaluate whether chemokine receptor CCR1 blockade late in the disease
      course can affect progression to renal failure. Mice were treated with
      subcutaneous injections of either vehicle or BX471, a nonpeptide CCR1 antagonist,
      three times a day from week 20 to 24 of age [corrected]. BX471 improved blood
      urea nitrogen levels (BX471, 35.1 +/- 5.3; vehicle, 73.1 +/- 39.6 mg/dl; P <
      0.05) and reduced the amount of ERHR-3 macrophages, CD3 lymphocytes, Ki-67
      positive proliferating cells, and ssDNA positive apoptotic cells in the
      interstitium but not in glomeruli. Cell transfer studies with fluorescence
      labeled T cells that were pretreated with either vehicle or BX471 showed that
      BX471 blocks macrophage and T cell recruitment to the renal interstitium of
      MRL(lpr/lpr) mice. This was associated with reduced renal expression of CC
      chemokines CCL2, CCL3, CCL4, and CCL5 and the chemokine receptors CCR1, CCR2, and
      CCR5. Furthermore, BX471 reduced the extent of interstitial fibrosis as evaluated
      by interstitial smooth muscle actin expression and collagen I deposits, as well
      as mRNA expression for collagen I and TGF-beta. BX471 did not affect serum DNA
      autoantibodies, proteinuria, or markers of glomerular injury in MRL(lpr/lpr)
      mice. This is the first evidence that, in advanced chronic renal injury, blockade
      of CCR1 can halt disease progression and improve renal function by selective
      inhibition of interstitial leukocyte recruitment and fibrosis.

PMID- 15153563
TI  - Increased infarct size in uremic rats: reduced ischemia tolerance?
AB  - In patients with renal failure, myocardial infarction (MI) is more frequent and
      the rate of death from acute MI is very high. It has been argued that ischemia
      tolerance of the heart is reduced in uremia, but direct evidence for this
      hypothesis has not been provided. It was the purpose of this study (1) to ligate
      the left coronary artery and to measure the nonperfused area (risk area: total
      infarction plus penumbra) as well as the area of total infarction in subtotally
      nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and
      (2) to examine the effects of potential confounders such as BP, sympathetic
      overactivity, and salt retention. The left coronary artery was ligated for 60
      min, followed by reperfusion for 90 min. For visualizing perfused myocardium,
      lissamine green ink was injected. The nonperfused area (lissamine exclusion) and
      the area of total infarction (triphenyltetrazolium chloride stain) were assessed
      in sections of the left ventricle using image analysis. Groups of SNX rats also
      received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high
      salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the
      nonperfused area at risk (as the proportion of total left ventricular area),
      presumably determined by the geometry of vascular supply, was similar in sham
      operated and SNX animals (0.38 +/- 0.13 versus 0.45 +/- 0.09; NS). In contrast,
      the infarcted area, given as a proportion of the nonperfused risk area, was
      significantly (P < 0.003) higher in SNX (0.68 +/- 0.09) compared with sham
      operated (0.51 +/- 0.11) rats and was not altered by any of the above
      interventions. The finding that a greater proportion of nonperfused myocardium
      undergoes total necrosis is consistent with the hypothesis of reduced ischemia
      tolerance of the heart in renal failure. The findings could explain the high rate
      of death from MI in patients with impaired renal function.

PMID- 15153565
TI  - Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17beta
      estradiol in the aging Dahl salt sensitive rat.
AB  - This study examined the effects of estrogen deficiency by ovariectomy (OVX) and
      17beta-estradiol (E(2)) replacement (OVX+E(2)) on glomerulosclerosis and
      tubulointerstitial fibrosis and the mechanisms contributing to these changes,
      including expression of collagen type IV and laminin, transforming growth factor
      beta (TGF-beta), and activity of matrix metalloproteinases (MMP) in the kidneys
      of young (4 mo [4M]) and aged (12 mo [12M]) Dahl salt-sensitive (DSS) rats
      maintained on a low-salt (0.1% NaCl) diet. While normal renal morphology was
      observed in the 4M rats in all treatment groups, moderate to severe
      glomerulosclerosis (glomerulosclerotic index [GSI]: 4M, 0.22 +/- 0.09 versus 12M,
      1.43 +/- 0.17; P < 0.001) and cortical tubulointerstitial fibrosis (CTIFI: 4M, 0
      versus 12M, 57.1 +/- 4.9; P < 0.01) was observed in the 12M rats. The severity of
      glomerulosclerosis and cortical tubulointerstitial fibrosis in the 12M group was
      augmented with OVX (GSI, 3.27 +/- 0.34; CTIFI, 74.4 +/- 9.2; P < 0.01 versus
      Intact at 12M) and attenuated with E(2) replacement ([GSI], 1.09 +/- 0.09; CTIFI,
      49.2 +/- 6.8). In the 12M animals, OVX was also associated with increased
      deposition and expression of laminin (Intact, 228.1 +/- 6.7; OVX, 277.4 +/- 9.6
      AU; P < 0.01), increased expression of TGF-beta (Intact, 85.0 +/- 23.0; OVX,
      178.0 +/- 20.5 AU; P < 0.001), and decreased activity of cortical MMP-9 (Intact,
      3.8 +/- 0.8; OVX, 2.4 +/- 0.6 AUC; P < 0.01). E(2) replacement opposed these
      effects (laminin, 229.9 +/- 6.2 AU; TGF-beta, 101.3 +/- 25.2 AU; MMP-9, 5.2 +/-
      0.2 AUC). The severity of the disease in the 12M rats correlated with a modest
      decrease in creatinine clearance (Intact, 0.26 +/- 0.01; OVX, 0.22 +/- 0.01;
      OVX+E(2), 0.28 +/- 0.01 mg/min per 100 g) and increase in BUN (Intact, 20.3 +/-
      2.1; OVX, 32.6 +/- 5.1; OVX+E(2), 24.3 +/- 2.4 mg/dl). The authors conclude that
      E(2) is renoprotective in the aging DSS rat by attenuating glomerulosclerosis and
      tubulointerstitial fibrosis.

PMID- 15153564
TI  - Regulation of muscle protein degradation: coordinated control of apoptotic and
      ubiquitin-proteasome systems by phosphatidylinositol 3 kinase.
AB  - Muscle proteolysis from catabolic conditions, including chronic kidney disease,
      requires coordinated activation of both the apoptotic and ATP-ubiquitin
      proteasome systems (Ub-P'some), including upregulation of components of the Ub
      P'some system. Activation of the apoptotic system is required because caspase-3
      initially cleaves myofibrils, yielding substrates for the Ub-P'some system plus a
      characteristic 14-kD actin fragment. The authors studied insulin deficiency, a
      model of accelerated muscle atrophy, to understand how regulation of the
      apoptotic and the Ub-P'some systems could be coordinated. As expected,
      phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in
      addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at
      serine-307. Caspase-3 activity was also increased, and the authors linked it to a
      low PI3K-induced activation of the apoptotic system that includes a
      conformational change in Bax and release of cytochrome C. Coordinated atrogin
      1/MAFbx expression is required as a critical factor for Ub-P'some system
      dependent muscle proteolysis in diabetes and other catabolic states. The
      mechanism that regulates atrogin-1/MAFbx expression is unknown. Atrogin-1/MAFbx
      expression increased when the authors suppressed PI3K activity in muscle cells.
      The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated
      atrogin-1/MAFbx promoter transcriptional activity markedly. The authors found in
      diabetic muscle that mRNA of the forkhead transcriptional factor, its nuclear
      translocation, and binding to the atrogin-1/MAFbx promoter were increased. When
      PI3K activity is low, both apoptotic and Ub-P'some pathways are activated
      coordinately to cause muscle proteolysis. This mechanism could increase muscle
      atrophy in conditions with impaired insulin responsiveness.

PMID- 15153567
TI  - Dependence of oxalate absorption on the daily calcium intake.
AB  - Two to 20% of ingested oxalate is absorbed in the gastrointestinal tract of
      healthy humans with a daily 800 mg calcium intake. Calcium is the most potent
      modifier of the oxalate absorption. Although this has been found repeatedly, the
      exact correlation between calcium intake and oxalate absorption has not been
      assessed to date. Investigated was oxalate absorption in healthy volunteers
      applying 0.37 mmol of the soluble salt sodium [(13)C(2)]oxalate in the calcium
      intake range from 5 mmol (200 mg) calcium to 45 mmol (1800 mg) calcium. Within
      the range of 200 to 1200 mg calcium per day, oxalate absorption depended linearly
      on the calcium intake. With 200 mg calcium per day, the mean absorption (+/- SD)
      was 17% +/- 8.3%; with 1200 mg calcium per day, the mean absorption was 2.6% +/-
      1.5%. Within this range, reduction of the calcium supply by 70 mg increased the
      oxalate absorption by 1% and vice versa. Calcium addition beyond 1200 mg/d
      reduced the oxalate absorption only one-tenth as effectively. With 1800 mg
      calcium per day, the mean absorption was 1.7% +/- 0.9%. The findings may explain
      why a low-calcium diet increases the risk of calcium oxalate stone formation.

PMID- 15153566
TI  - Differential inhibition of HSP72 and HSP25 produces profound impairment of
      cellular integrity.
AB  - To test a putative cause and effect relationship between heat-shock protein (HSP)
      expression and response to renal cell injury, HSP72 and HSP25 were differentially
      inhibited in LLC-PK1 cells by means of transcription factor decoy and short
      interference RNA (siRNA). Cellular injury was assessed by solubilization of NaK
      ATPase (S-NaK). An exonuclease-resistant, ethylene glycol-bridged, circular
      oligonucleotide decoy for heat-shock transcription factor (HSF)-1, based on the
      sequence of the porcine heat-shock element, was constructed and validated. It was
      found that under all experimental conditions, cells had comparable ATP levels;
      that decoy of unligated or scrambled sequence was ineffective; that HSP72 mRNA
      and HSP72/HSP25 proteins were significantly reduced in decoy-treated cells; and
      that the dampened response to HSF activation in decoy-treated, injured cells was
      accompanied by a substantially amplified loss of cellular integrity (S-NaK was
      85% compared with baseline levels). Specific inhibition of HSP72 that used siRNA
      directed against an inducible porcine HSP72 gene resulted in complete ablation of
      injury-induced HSP72. Isolated inhibition of HSP72 was also associated with
      marked NaK ATPase detachment from the cytoskeleton (S-NaK was 135% compared with
      baseline levels). These studies suggest that an HSF-1 decoy effectively dampens
      the HSP72/HSP25 response to injury in renal cells; that HSP72 siRNA ablates
      injury-induced induction of HSP72; and that dampening of the HSP72/HSP25 response
      and ablation of the HSP72 response are both associated with impaired restitution
      of cellular polarity.

PMID- 15153568
TI  - Hypoperfusion of peritubular capillaries induces chronic hypoxia before
      progression of tubulointerstitial injury in a progressive model of rat
      glomerulonephritis.
AB  - Chronic hypoxia likely plays a pivotal role in chronic renal disease, but the
      specifics of its involvement remain unclear. To elucidate how chronic hypoxia
      occurs and whether hypoxia participates in the progression of renal disease, the
      authors established an irreversible glomerulonephritis model induced by
      uninephrectomy and repeated anti-Thy-1 antibody injections. Glomerulosclerosis
      with microvascular obliteration was complete at 2 wk after antibody injection and
      was not restored until 11 wk. Tubulointerstitial injury was mild at 2 wk and was
      gradually exacerbated until 11 wk, a pattern that was in accordance with the loss
      of peritubular capillaries. Immunohistochemical analysis using pimonidazole
      revealed the augmentation of hypoxia in the cortex before the aggravation of
      tubulointerstitial injury and subsequent peritubular capillary loss. The
      preexistence of hypoxia implies that it had substantial participation in the
      progression of tubulointerstitial injury. To test whether blood flow was
      inhibited in diseased kidneys, capillaries with intact blood flow were identified
      by tail vein injection of biotinylated lectin specific to endothelial cells. The
      renal microvasculature was well recognized by lectin in the controls, whereas
      lectin binding to peritubular capillaries was strikingly decreased in diseased
      kidneys, suggesting a disturbance of blood flow. Intravital microscopy analysis
      confirmed that blood flow in peritubular capillaries was decreased by
      approximately 40% in the disease group compared with the controls. In conclusion,
      stagnation of blood flow in peritubular capillaries induced chronic hypoxia at an
      early stage in this model, which was followed by progressive tubulointerstitial
      injury and a loss of peritubular capillaries.

PMID- 15153569
TI  - Malignancy in renal transplantation.

PMID- 15153570
TI  - Acute metabolic acidosis: characterization and diagnosis of the disorder and the
      plasma potassium response.
AB  - ABSTRACT. Despite the high incidence of acute metabolic acidosis, there are no
      reliable human data to enable physicians to accurately diagnose this disorder. In
      addition, there is uncertainty about the direction and magnitude of plasma
      potassium changes in acute metabolic acidosis. The systemic and renal acid-base,
      electrolyte, and endocrine response to acute acid loads (imposed by three timed
      NH(4)Cl infusions into the duodenum, 0.9 mmol of NH(4)Cl per kg of body weight
      over 30 min each) was characterized in six healthy male subjects in whom a
      metabolic steady-state had been established. Arterialized blood CO(2) tension
      decreased by 0.85 mmHg per mmol/L decrease in plasma bicarbonate concentration
      and blood hydrogen ion concentration increased by 0.45 nmol/L per mmol/L decrease
      in plasma bicarbonate concentration. Plasma potassium did not change
      significantly (+0.02 +/- 0.02 mmol/L per mmol decrease in plasma bicarbonate
      concentration). Plasma insulin increased and plasma glucagon levels decreased in
      acute metabolic acidosis, while catecholamines and aldosterone were not affected
      significantly. These data provide the first diagnostic criteria for the diagnosis
      of acute metabolic acidosis in humans. The finding of a hyperinsulinemic response
      in acute metabolic acidosis suggests that an insulin response counterregulates
      any acidemia-induced cellular potassium efflux, resulting in stable plasma
      potassium concentrations.

PMID- 15153571
TI  - Minimal changes of serum creatinine predict prognosis in patients after
      cardiothoracic surgery: a prospective cohort study.
AB  - Acute renal failure increases risk of death after cardiac surgery. However, it is
      not known whether more subtle changes in renal function might have an impact on
      outcome. Thus, the association between small serum creatinine changes after
      surgery and mortality, independent of other established perioperative risk
      indicators, was analyzed. In a prospective cohort study in 4118 patients who
      underwent cardiac and thoracic aortic surgery, the effect of changes in serum
      creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox
      regression was used to correct for various established demographic preoperative
      risk indicators, intraoperative parameters, and postoperative complications. In
      the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in
      contrast to 8.9% in patients with increased postoperative serum creatinine
      values. Patients with large decreases (DeltaCrea <-0.3 mg/dl) showed a
      progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest
      (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum
      of -0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine
      remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%])
      was highest in patients in whom creatinine increased > or =0.5 mg/dl. For all
      groups, increases in mortality remained significant in multivariate analyses,
      including postoperative renal replacement therapy. After cardiac and thoracic
      aortic surgery, 30-d mortality was lowest in patients with a slight postoperative
      decrease in serum creatinine. Any even minimal increase or profound decrease of
      serum creatinine was associated with a substantial decrease in survival.

PMID- 15153572
TI  - Kidney protein dynamics and ammoniagenesis in humans with chronic metabolic
      acidosis.
AB  - To evaluate the effects of chronic metabolic acidosis on protein dynamics and
      amino acid oxidation in the human kidney, a combination of organ isotopic ((14)C
      leucine) and mass-balance techniques in 11 subjects with normal renal function
      undergoing venous catheterizations was used. Five of 11 studies were performed in
      the presence of metabolic acidosis. In subjects with normal acid-base balance,
      kidney protein degradation was 35% to 130% higher than protein synthesis, so net
      protein leucine balance was markedly negative. In acidemic subjects, kidney
      protein degradation was no different from protein synthesis and was significantly
      lower (P < 0.05) than in controls. Kidney leucine oxidation was similar in both
      groups. Urinary ammonia excretion and total ammonia production were 186% and 110%
      higher, respectively, and more of the ammonia that was produced was shifted into
      urine (82% versus 65% in acidemic subjects versus controls). In all studies,
      protein degradation and net protein balance across the kidney were inversely
      related to urinary ammonia excretion and to the partition of ammonia into urine,
      but not to total ammonia production, arterial pH, [HCO(-)(3)], urinary flow, the
      uptake of glutamine by the kidney, or the ammonia released into the renal veins.
      The data show that response of the human kidney to metabolic acidosis includes
      both changes in amino acid uptake and suppression of protein degradation. The
      latter effect, which is likely induced by the increase in ammonia excretion and
      partition into the urine, is potentially responsible for kidney hypertrophy.

PMID- 15153573
TI  - Development of chronic kidney disease and cardiovascular prognosis in essential
      hypertensive patients.
AB  - The existence of a significant percentage of treated hypertensive patients
      presenting a diminished renal function has been recently described. Mild renal
      function abnormalities are recognized as powerful predictors of cardiovascular
      morbidity and mortality. However, longitudinal data demonstrating this
      association are lacking. The objectives of this study have been analysis of the
      evolution of GFR, assessed as creatinine clearance (CrCl), during long-term
      follow-up of hypertensive patients and evaluation of the impact of the
      development of chronic kidney disease (CKD) on cardiovascular prognosis. A
      historical cohort of 281 patients attending our Hypertension Unit was selected
      according to the following criteria: essential hypertension, more than 5 yr of
      follow-up, and normal GFR at baseline (CrCl > 90 ml/min per 1.73 m(2)). Patients
      had an average follow-up of 13.2 +/- 4.8 yr. Forty-one patients (14.6%) developed
      CKD (CrCl < 60 ml/min per 1.73 m(2)) attributed to hypertensive nephrosclerosis.
      Initial serum creatinine, age, systolic BP at baseline, and average total
      cholesterol during follow-up were independent predictors of CKD development.
      Forty-nine (17.4%) of 281 patients presented a cardiovascular event during follow
      up: 17 patients (40.6%) who developed CKD and 32 patients (13.3%) with preserved
      renal function (log rank test P < 0.001). After adjustment in a Cox multivariate
      analysis, age, development of CKD during follow-up, and male gender were
      independent predictors of the appearance of cardiovascular events. In essential
      hypertensive patients with normal renal function at baseline, the development of
      CKD during the follow-up is strongly and independently related with poor
      cardiovascular prognosis.

PMID- 15153574
TI  - Administration of parenteral iron and mortality among hemodialysis patients.
AB  - The objective of this study was to evaluate whether the apparent relationship
      demonstrated in prior studies between iron dosing and mortality in hemodialysis
      (HD) patients was confounded by incomplete representation of iron dosing and
      morbidity over time. A cohort study was conducted among 32,566 patients who
      received at least 1 yr of HD at the Fresenius Medical Corporation dialysis
      centers during 1996 to 1997. The outcome measure was all-cause mortality through
      mid-1998. A total of 19 demographic, comorbidity, and laboratory characteristics
      were available. By proportional hazards analysis, no adverse effect on 2-year
      survival was found for baseline iron dose over 6 mo of < or = 1000 mg, but
      statistically significant elevated mortality was demonstrated for iron doses
      >1000 mg to 1800 mg (adjusted hazards ratio [HR] = 1.09; 95% confidence interval
      [CI], 1.01 to 1.17) and >1800 mg (adjusted HR = 1.18; 95% CI, 1.09 to 1.27).
      However, fitting multivariable models that appropriately account for time-varying
      measures of iron administration as well as other fixed and time-varying measures
      of morbidity, the authors found no statistically significant association between
      any level of iron administration and mortality. This study suggests that
      previously observed associations between iron administration and higher mortality
      may have been confounded, and it provides cautious support for the safety of the
      judicious administration of cumulative iron doses >1000 mg over 6 mo if needed to
      maintain target hemoglobin levels among patients treated with maintenance HD.

PMID- 15153575
TI  - Human immunodeficiency virus infection and kidney transplantation in the era of
      highly active antiretroviral therapy and modern immunosuppression.
AB  - Before the era of highly active antiretroviral therapy, kidney transplant
      recipients infected with HIV had increased risk of death compared with HIV
      uninfected recipients. More recent single-center reports have indicated improved
      results, but this has not been assessed in a national population. Therefore, a
      retrospective cohort study of US adult deceased donor kidney transplant
      recipients from January 1, 1996, to May 31, 2001 was conducted; patients were
      followed until October 31, 2001. A total of 27,851 patients had valid recipient
      HIV serology. Cox regression analysis was used to model adjusted hazard ratios
      for mortality and graft loss, respectively, adjusted for other factors, including
      comorbid conditions from Centers for Medicare and Medicaid Studies Form 2728.
      Factors independently associated with HIV infection were also assessed by
      logistic regression analysis. Only 12.8% of HIV-infected recipients were black,
      compared with 27.6% in the entire study cohort. HIV-infected kidney transplant
      recipients were significantly less likely to be black in logistic regression
      analysis (adjusted OR, 0.29; 95% CI, 0.08 to 0.99; P = 0.049), which was the only
      factor independently associated with HIV infection. It was found that HIV
      infected recipients had improved survival compared with HIV-uninfected
      recipients, although this was not statistically significant in adjusted analysis
      (adjusted HR, 0.36; 95% CI, 0.05 to 2.53; P = 0.31). Kidney transplantation in
      HIV-infected patients is plausible and ongoing, but HIV-infected candidates who
      underwent kidney transplantation in the United States during the course of the
      study were demographically unrepresentative of HIV-infected candidates generally.

PMID- 15153576
TI  - Development, prevention, and potential reversal of left ventricular hypertrophy
      in chronic kidney disease.
AB  - Although a high prevalence of left ventricular (LV) hypertrophy is recognized
      with increasing severity of chronic kidney disease (CKD), previously neither its
      progression nor its potential for prevention or reversal has been addressed
      adequately in this population group. A nested analysis of a 2-yr study involving
      155 patients with stage 3/4 CKD, examining effects of hemoglobin change (range,
      90 to 130 g/L) on LV mass in patients with (n = 46; 30%) and without (n = 105;
      70%) initial LV hypertrophy, is reported. At baseline, the group with LV
      hypertrophy was older (P < 0.01), had higher BP (P < 0.01), had greater LV wall
      and cavity dimensions (P < 0.001), and had more prevalent use of antihypertensive
      agents (P < 0.001) but a lower hemoglobin concentration (P < 0.05) and GFR (P <
      0.01). A total of 117 patients were available for assessment at 2 yr.
      Importantly, 57 (68%) with initial normal LV indices showed no appreciable change
      with time; however, 27 (32%) developed LV hypertrophy, with growth in both wall
      and cavity dimensions (P < 0.001). In contrast, 23 (50%) of those with initial LV
      hypertrophy maintained elevated LV indices, whereas 10 (22%) regressed, through
      wall but not cavity reduction, to within normal LV indices. Predisposing factors
      to maintaining or achieving normal LV mass dimensions included relative youth (P
      < 0.05), a lower pulse pressure (P < 0.05), and a higher GFR (P < 0.05) but not
      hemoglobin concentration or parathyroid hormone levels. These findings suggest
      that even at a relatively advanced stage of renal dysfunction, control of BP and
      volume, together with regulated metabolic and clinical indices, may contribute to
      the prevention or even reversal of LV hypertrophy in a substantial proportion of
      patients.

PMID- 15153578
TI  - Incorporating recipient choice in kidney transplantation.
AB  - Despite the acute shortage of cadaveric organs for kidney transplantation, more
      than 10% of cadaveric kidneys are discarded each year because of marginal
      quality. Transplant recipients' access to these kidneys and to information about
      their quality is limited. A Monte Carlo model was developed to simulate the
      operations of an organ procurement organization over a 10-yr period. Donor and
      recipient characteristics were generated from the United States Renal Data
      System. Kidneys were assigned one of five possible grades, which were determined
      by calculating the relative risk of graft failure associated with donor
      characteristics and HLA matching for every donor-candidate pair. Modeled were
      recipient decisions to accept or reject a kidney on the basis of the relative
      change in quality-adjusted life years (QALY). Compared were the United Network of
      Organ Sharing (UNOS) policy, the UNOS expanded donor criteria policy, two
      benchmark policies (one equity driven and the other efficiency driven), and a
      hybrid policy that incorporated recipient choice into the UNOS algorithm.
      Sensitivity analyses for major input variables were performed. Compared with
      UNOS, an algorithm that incorporated recipient choice predicted a 6% increase in
      QALY, a 12% decrease in median waiting time, a 39% increase in the likelihood of
      transplantation, and a 56% reduction in the number of discarded kidneys. Benefits
      were observed across categories of age, gender, and race. Incorporating recipient
      choice in kidney transplantation would improve equity, efficiency, and QALY of
      the end-stage renal disease population.

PMID- 15153577
TI  - Non-transferrin-bound iron in the serum of hemodialysis patients who receive
      ferric saccharate: no correlation to peroxide generation.
AB  - Intravenous iron (iv.Fe) is used to optimize response to recombinant human
      erythropoietin (r-HuEPO) in ESRD, but no consensus exists with respect to the
      best regimen to avoid transferrin "oversaturation," oxidative stress, and the
      occurrence of non-transferrin-bound iron (NTBI). Iv.Fe was stopped for 1 wk in 35
      hemodialysis (HD) patients who were routinely receiving iv.Fe and r-HuEPO. The
      iv.Fe group received 100 mg of ferric saccharate (Venofer) at the end of the
      first HD session, whereas the time-control group was treated under the same
      conditions but received no iv.Fe. Serum samples were taken before the first HD
      session, immediately and 60 min after iv.Fe administration, and before the next
      HD session. Sera were analyzed for NTBI and peroxides; transferrin saturation was
      analyzed by urea-PAGE and Western blot. In an in vitro model system with HepG2
      cells, the effects of ESRD serum on the labile iron pool (LIP) were assayed using
      the fluorescence calcein assay. NTBI significantly increased after iv.Fe
      administration and returned to baseline values before the next HD-session. There
      was a shift from apo- to monoferric transferrin, but no "oversaturation" of
      transferrin after iv.Fe-treatment. Peroxides increased in both groups after HD.
      Hemodialysis decreased bioavailable iron for the LIP in HepG2-cells, whereas
      serum of iv.Fe-treated HD patients highly increased the LIP in these cells. A
      total of 100 mg of iv.Fe led to NTBI generation but not to an oversaturation of
      transferrin. Peroxide concentrations significantly increased during HD but were
      not correlated to iv.Fe administration and seemed to result from other sources of
      oxidative stress related to HD. NTBI can enter liver cells and increase the
      potentially harmful LIP.

PMID- 15153579
TI  - Pathophysiology underlying accelerated atherogenesis in renal disease: closing in
      on the target.

PMID- 15153580
TI  - PCO2 and [K+]p in metabolic acidosis: certainty for the first and uncertainty for
      the other.

PMID- 15153582
TI  - The need for randomized controlled trials in podiatric medical research.
AB  - The randomized controlled trial is the most robust method available to evaluate
      health-care treatments. If podiatric medical practice is to be based on rigorous
      evidence, then high-quality randomized controlled trials are needed to inform
      that practice. In this article, we examine the extent to which randomized
      controlled trials are used in recent podiatric medical research and appraise the
      quality of those that are available. Using the Cochrane database of all
      randomized controlled trials in health care, we found only six relevant trials
      undertaken in podiatric medicine since 1997. These studies were of variable
      quality. We also discuss the key features of a rigorous trial design. To date,
      the clinical practice of podiatric medicine is not adequately informed by the
      best available evidence. We call for more high-quality randomized controlled
      trials to be undertaken in podiatric medical research.

PMID- 15153583
TI  - Evaluating the clinical effectiveness and cost-effectiveness of foot orthoses in
      the treatment of plantar heel pain: a feasibility study.
AB  - This study evaluated the clinical effectiveness and cost-effectiveness of two
      different types of foot orthoses used to treat plantar heel pain. Forty-eight
      patients were randomly assigned to receive either a functional or an
      accommodative orthosis. General (EuroQol) and specific (Foot Health Status
      Questionnaire) health-status measures were used. Data were also collected using
      economic questionnaires relating to National Health Service costs for podiatry,
      other health-service costs, and patient costs. Data were measured at baseline and
      at 4- and 8-week intervals. Thirty-five patients completed the study. The results
      demonstrated a significant decrease in foot pain and a significant increase in
      foot function with the functional foot orthoses over the 8-week trial. The
      accommodative foot orthoses demonstrated a significant reduction in foot pain
      only at 4 weeks. The cost-effectiveness analysis demonstrated that functional
      orthoses, although initially more expensive, result in a better quality of life.
      Use of functional orthoses resulted in an increased cost of pound 17.99 (32.74
      dollars) per patient, leading to an incremental cost per quality-adjusted life
      year of pound 1,650 (3,003 dollars) for functional orthoses.

PMID- 15153584
TI  - Plantar pressures in rheumatoid arthritis using prefabricated metatarsal padding.
AB  - We sought to determine whether one of two prefabricated insole designs could
      better manage high forefoot plantar pressures in patients with rheumatoid
      arthritis. Ten subjects with rheumatoid arthritis who experienced pain with shod
      weightbearing were studied by using a plantar pressure measurement system. Two
      insole designs and a shoe-only control condition were randomly tested in repeated
      trials. Dome- and bar-shaped metatarsal pads made of latex foam were incorporated
      into full-length insoles made of urethane. Significant reductions in mean peak
      plantar pressures over the central metatarsals were noted when using the insole
      and dome pad design (12% [33 kPa]) and the insole and bar pad design (21% [58
      kPa]) compared with the shoe-only condition. A prefabricated insole design
      incorporating a bar metatarsal pad is recommended to manage high forefoot plantar
      pressures in patients with rheumatoid arthritis.

PMID- 15153586
TI  - Effect of orthotic therapy on claw toe loading: results of significance testing
      at pressure sensor units.
AB  - This study demonstrates the effect of orthotic therapy for toe deformity on toe
      and metatarsal head pressures using a new analysis method facilitated by an in
      shoe pressure-measurement system's ability to export detailed data. Plantar
      pressure-time integrals in 11 individuals (22 feet) with claw deformity of the
      lesser toes were measured with and without toe props. Differences in pressure
      time integrals at every individual sensor unit were then calculated for the two
      conditions, and significance was tested using the paired t-test. Plantar surface
      charts with contours of equal significant pressure-time integral change showed
      significant reduction under 17 second toes (77%), 22 third toes (100%), 15 fourth
      toes (68%), 13 second metatarsal heads (59%), 16 third metatarsal heads (73%),
      and 16 fourth metatarsal heads (73%). All 22 feet showed increases under the prop
      in the area of the third toe sulcus. This innovative approach to plantar pressure
      analysis could improve access to data that show significant pressure-time
      integral changes and, therefore, could advance the clinical application of
      plantar pressure measurement.

PMID- 15153587
TI  - Forefoot plantar pressures in rheumatoid arthritis.
AB  - We sought to investigate the magnitude and duration of peak forefoot plantar
      pressures in rheumatoid arthritis. The spatial and temporal characteristics of
      forefoot plantar pressures were measured in 25 patients with a positive diagnosis
      of rheumatoid arthritis of 5 to 10 years' duration (mean, 8 years) and a
      comparison group using a platform-based pressure-measurement system. There were
      no significant differences between groups in the magnitude of peak plantar
      pressure in the forefoot region. Significant differences were, however, noted for
      temporal aspects of foot-pressure measurement. The duration of loading over
      sensors detecting peak plantar pressure was significantly longer in the
      rheumatoid arthritis group. In addition, the rheumatoid arthritis group
      demonstrated significantly greater force-time integrals. Significant increases in
      the temporal parameters of plantar pressure distribution, rather than those of
      amplitude, may be characteristic of the rheumatoid foot.

PMID- 15153588
TI  - A theory of shoe wear pattern influence incorporating a new paradigm for the
      podiatric medical profession.
AB  - Qualitative analysis of shoe wear patterns collected from a questionnaire
      evaluating podiatric physicians' experiences in this area suggests that wear
      patterns could indicate causative function within a known pathologic context.
      Several different functions are suggested by patterns associated with each of the
      pathologic entities involved, and analysis of the relationship between patterns
      and reasons given by respondents for pattern-form variations show the strongest
      associations to be with functionally termed conditions. A basic model is proposed
      to present factors important in wear pattern production, suggesting that a new
      concept of primary walking intention is more influential than foot pathologies in
      wear pattern formation and that external factors are also influential, with the
      combined factors being described as the "holistic foot function." This model may
      provide a variety of benefits to podiatric medicine; as shoe wear patterns are
      records of the usual long-term activity of the functioning foot, this paradigm
      could form a basis for podiatric medical practice.

PMID- 15153589
TI  - Sagittal plane compensations for artificially induced limitation of the first
      metatarsophalangeal joint: a preliminary study.
AB  - This study was undertaken to establish whether reduced dorsiflexion at the first
      metatarsophalangeal joint affects sagittal plane kinematics at the ankle, knee,
      and hip. Twenty individuals with symptom-free metatarsophalangeal joints were
      studied as they walked with and without an insole designed to restrict first
      metatarsophalangeal joint dorsiflexion. Sagittal plane kinematics at the ankle,
      knee, and hip were compared in the two conditions. When walking with the insole,
      the ankle was more dorsiflexed during late midstance and less plantarflexed
      during propulsion, the knee was more flexed during midstance, and the hip was
      less extended during late midstance. This evidence of a link between the first
      metatarsophalangeal joint and the kinematics of the proximal joints demonstrates
      the potential for the clinical entities of hallux rigidus and hallux limitus to
      influence gait and justifies more detailed study of this relationship.

PMID- 15153590
TI  - Examining the validity of selected measures of foot type: a preliminary study.
AB  - The rationale that subtalar joint position, reflected by calcaneal alignment,
      determines foot morphology was used to formulate an approach to examination of
      the validity of three measures of "foot type": the Staheli Arch Index, the
      Chippaux-Smirak Index, and navicular height. Each measure was calculated in five
      positions, progressively inverting from a reference position of maximal
      comfortable eversion. Pearson product moment correlations (Staheli Arch Index: r
      = 0.5; Chippaux-Smirak Index: r = 0.6; and navicular height: r = 0.8) indicated
      that each measure progressively increased with inversion. The change in calcaneal
      position required to produce significant changes in each measure was investigated
      using analysis of variance with Scheffe post hoc analysis. This analysis revealed
      that changes of 15 degrees and 20 degrees were required to produce significant
      differences in Chippaux-Smirak Index and Staheli Arch Index scores, respectively,
      threatening their validity. Navicular height was sensitive to smaller changes of
      10 degrees and thus displays greater sensitivity to changes in calcaneal position
      than the footprint parameters tested.

PMID- 15153591
TI  - Burnout and occupational stress: comparison between United Kingdom and Australian
      podiatrists.
AB  - Professional and occupational burnout is a recognized syndrome among healthcare
      professionals, although the point at which burnout begins is unclear. There is a
      dearth of research investigating burnout and occupational stress in relation to
      podiatric medicine, although two recent studies have reported high levels of
      burnout expressed by podiatric medical practitioners. This study was undertaken
      to compare the levels of burnout in newly qualified practitioners in Australia
      and the United Kingdom. The results suggest that levels of burnout are higher in
      these groups than indicated by the published normative medical data. Occupational
      stress was associated with lack of professional status and with geographic and
      professional isolation. Within these two themes, there were clear differences
      between the two groups.

PMID- 15153592
TI  - Foot problems in older patients: a focused podogeriatric assessment study in
      ambulatory care.
AB  - This study sought to demonstrate the prevalence of foot conditions in older
      individuals and their association with chronic risk diseases such as diabetes
      mellitus, peripheral arterial disease, and arthritis, and to develop care plans
      to reduce complications from local foot problems and chronic diseases. One
      thousand individuals older than 65 years who were ambulatory and not
      institutionalized underwent a standardized and validated podogeriatric
      examination assessment protocol or index. Overall, 74.6% of all patients had a
      history of pain, 57.2% were receiving current care for diabetes mellitus, 22.9%
      indicated current care for peripheral vascular disease, 94.2% had
      onychodystrophy, 64.2% had one or more foot deformities, 64.0% demonstrated some
      loss of protective sensation, and 81.7% had one or more symptoms and signs of
      peripheral arterial insufficiency. These findings demonstrate that foot problems
      in the older population result from disease, disability, and deformity related to
      multiple chronic diseases as well as changes associated with repetitive use and
      trauma. Older people are at a high risk of developing foot-related disease and
      should receive continuing foot assessment, education, surveillance, and care.

PMID- 15153594
TI  - Radiography of soft tissue of the foot and ankle with diffraction enhanced
      imaging.
AB  - Non-calcified tissues, including tendons, ligaments, adipose tissue and
      cartilage, are not visible, for any practical purposes, with conventional X-ray
      imaging. Therefore, any pathological changes in these tissues generally
      necessitate detection through magnetic resonance imaging or ultrasound
      technology. Until recently the development of an X-ray imaging technique that
      could detect both bone and soft tissues seemed unrealistic. However, the
      introduction of diffraction enhanced X-ray imaging (DEI) which is capable of
      rendering images with absorption, refraction and scatter rejection qualities has
      allowed detection of specific soft tissues based on small differences in tissue
      densities. Here we show for the first time that DEI allows high contrast imaging
      of soft tissues, including ligaments, tendons and adipose tissue, of the human
      foot and ankle.

PMID- 15153593
TI  - Analgesic efficacy of preoperative parecoxib sodium in an orthopedic pain model.
AB  - The efficacy and safety of preoperative intravenous administration of parecoxib
      sodium, a novel parenteral prodrug of a cyclooxygenase-2 selective inhibitor, in
      treating postoperative pain resulting from bunionectomy were evaluated in 50
      patients who were part of a larger cohort of orthopedic and podiatric patients.
      Following bunionectomy, the median time to rescue medication (survival analysis)
      was 4 hours 18 min (95% confidence interval, 3 hours 4 min to 4 hours 37 min) in
      the placebo group, 7 hours 5 min (95% confidence interval, 3 hours 20 min to >24
      hours) in the 20-mg parecoxib sodium group, and 10 hours 43 min (95% confidence
      interval, 4 hours 42 min to 14 hours 7 min) in the 40-mg parecoxib sodium group
      (significant for 40-mg parecoxib sodium versus placebo). Four or more hours after
      surgery, the mean pain-intensity (categorical) score was significantly lower in
      both parecoxib sodium groups than in the placebo group. Preoperative
      administration of parecoxib sodium was well tolerated and significantly reduced
      postoperative pain in patients who had undergone bunionectomy.

PMID- 15153595
TI  - Council on Podiatric Medical Education Eighty-fourth Annual Report, 2003.

PMID- 15153598
TI  - Two steps forward: keeping the momentum in stem cell research.

PMID- 15153600
TI  - Electroporation of murine embryonic stem cells: a step-by-step guide.
AB  - The manipulation of embryonic stem (ES) cells to generate targeted mutations via
      homologous recombination has proved an invaluable resource for researchers from
      fields as diverse as embryology, immunology, physiology, and biophysics. The
      derivation and culture of these cells has been described in many places, but
      there is no substitute for hands-on experience. In lieu of that, here we provide
      a step-by-step guide for the technique of electroporation, complete with
      micrographs of the cells at each step of the process. This is intended to allow
      the first time ES cell worker, as well as the more experienced researcher, to
      view the morphology of ES cells under ideal conditions as well as when the cells
      are suboptimal and should be discarded.

PMID- 15153601
TI  - Differentiating stem cells mask their origins.

PMID- 15153602
TI  - Cell-cell contact and anatomical compatibility in stromal cell-mediated HSC
      support during development.
AB  - Hematopoietic stem cells (HSCs) are able to generate the wide variety of blood
      cells found in the adult and are maintained in the bone marrow (BM) stromal
      microenvironment. In the aorta-gonads-mesonephros (AGM), which autonomously
      generates the first HSCs, the stromal microenvironment is largely
      uncharacterized. We have previously made an extensive panel of stromal clones
      from AGM subregions and have found that clones from the urogenital ridges (UG)
      provide the most potent support for adult BM HSCs. However, it is unknown to what
      extent the stroma from this developmentally and anatomically distinct
      microenvironment can support HSCs from other regions of the embryo, such as yolk
      sac. Moreover, it is unknown whether cell-cell contact is necessary in this
      microenvironment. Here, we show that the HSCs from the embryonic aorta are the
      most potently supported HSCs in UG stromal clone co-cultures and that contact is
      required for the maintenance and expansion of embryo-derived HSCs.

PMID- 15153603
TI  - Redox regulation of the embryonic stem cell transcription factor oct-4 by
      thioredoxin.
AB  - Oct-4 is a transcriptional regulator required to maintain the totipotentiality of
      embryonic stem (ES) cells. Downregulation of its activity is required for proper
      differentiation of the blastocyst during uterine implantation. Uterine
      implantation and subsequent vascularization increase oxygen exposure of the
      developing embryo, thereby altering the intracellular reduction-oxidation status.
      We tested whether Oct-4 could be regulated by these changes in reduction
      oxidation status. We found that Oct-4 DNA binding was exquisitely sensitive to
      abrogation by oxidation but that the DNA binding of another ES cell transcription
      factor, FoxD3, was much less sensitive to oxidation. The reducing enzyme
      Thioredoxin (but not Ape-1) could restore DNA-binding activity of Oct-4.
      Thioredoxin was less effective at restoring the DNA-binding ability of FoxD3. It
      was also found that Thioredoxin (but not Ape-1) could physically associate with
      cysteines in the POU domain of Oct-4. Finally, overexpressing normal Thioredoxin
      increased the transcriptional activity of Oct-4, while overexpressing a mutant
      Thioredoxin decreased the transcriptional activity of Oct-4. These data imply
      that ES cell transcription factors are differentially sensitive to oxidation and
      that Thioredoxin may differentially regulate ES cell transcription factors.

PMID- 15153605
TI  - Controlled, scalable embryonic stem cell differentiation culture.
AB  - Embryonic stem (ES) cells are of significant interest as a renewable source of
      therapeutically useful cells. ES cell aggregation is important for both human and
      mouse embryoid body (EB) formation and the subsequent generation of ES cell
      derivatives. Aggregation between EBs (agglomeration), however, inhibits cell
      growth and differentiation in stirred or high-cell-density static cultures. We
      demonstrate that the agglomeration of two EBs is initiated by E-cadherin-mediated
      cell attachment and followed by active cell migration. We report the development
      of a technology capable of controlling cell-cell interactions in scalable culture
      by the mass encapsulation of ES cells in size-specified agarose capsules. When
      placed in stirred-suspension bioreactors, encapsulated ES cells can be used to
      produce scalable quantities of hematopoietic progenitor cells in a controlled
      environment.

PMID- 15153604
TI  - Differentiation of human embryonic stem cells into insulin-producing clusters.
AB  - Type I diabetes mellitus is caused by an autoimmune destruction of the insulin
      producing beta cells. The major obstacle in using transplantation for curing the
      disease is the limited source of insulin-producing cells. The isolation of human
      embryonic stem (hES) cells introduced a new prospect for obtaining a sufficient
      number of beta cells for transplantation. We present here a method for forming
      immature islet-like clusters of insulin-producing cells derived from hES cells.
      The protocol consisted of several steps. Embryoid bodies were first cultured and
      plated in insulin-transferrin-selenium-fibronectin medium, followed by medium
      supplemented with N2, B27, and basic fibroblast growth factor (bFGF). Next, the
      glucose concentration in the medium was lowered, bFGF was withdrawn, and
      nicotinamide was added. Dissociating the cells and growing them in suspension
      resulted in the formation of clusters which exhibited higher insulin secretion
      and had longer durability than cells grown as monolayers. Reverse transcription
      polymerase chain reaction detected an enhanced expression of pancreatic genes in
      the differentiated cells. Immunofluorescence and in situ hybridization analyses
      revealed a high percentage of insulin-expressing cells in the clusters. In
      addition to insulin, most cells also coexpressed glucagon or somatostatin,
      indicating a similarity to immature pancreatic cells. Further improvement of this
      insulin-producing cell protocol may lead to the formation of an unlimited source
      of cells suitable for transplantation.

PMID- 15153606
TI  - Tumor necrosis factor alpha enhances the adenoviral transduction of CD34+
      hematopoietic progenitor cells.
AB  - The purpose of this study was to improve the transduction efficiency of
      adenoviral vectors (Ad) in human CD34+ hematopoietic progenitor cells. CD34+
      cells from cord blood or mobilized peripheral blood were incubated with tumor
      necrosis factor-alpha (TNF-alpha). After removal of free TNF-alpha, the cells
      were infected with an Ad encoding green fluorescent protein (GFP). One day later,
      viable cells were counted and analyzed for GFP and CD34 by flow cytometry. To
      visualize vectoral trafficking, CD34+ cells were incubated with fluorophore
      conjugated Ad. Plating efficiencies of hematopoietic progenitors before and after
      transduction were evaluated by methylcellulose assays. Pretreatment with TNF
      alpha increased the transduction efficiency more than twofold (39.2% versus
      15.5%) in a dose-dependent manner and strongly improved the survival of GFP
      positive CD34+ cells. Time course experiments showed that TNF-alpha incubation
      times as short as 10 minutes were still effective. Neutralizing antibodies to TNF
      receptor II and RGD peptides diminished the TNF-alpha-dependent increase in
      transduction efficiency. No TNF-alpha-dependent increase in adenoviral receptors
      (coxsackie-adenovirus receptor, alphavbeta3-integrin) occurred. Analysis of viral
      binding demonstrated a significantly higher incidence of local concentrations of
      Ad along the cell surface (caps) in virus-positive cells of the TNF-alpha-treated
      group. Plating efficiency, especially the formation of granulocyte-macrophage
      colony forming units, was enhanced by TNF-alpha pretreatment. We conclude that
      brief incubation with TNF-alpha before addition of the Ad significantly increased
      the Ad transduction efficiency in CD34+ cells, and improved post-transduction
      survival of progenitors of the granulocyte-macrophage lineage. This finding
      correlates with increased Ad capping at the cell surface and suggests an
      alteration of Ad trafficking.

PMID- 15153607
TI  - Properties of pluripotent human embryonic stem cells BG01 and BG02.
AB  - Human ES (hES) cell lines have only recently been generated, and differences
      between human and mouse ES cells have been identified. In this manuscript we
      describe the properties of two human ES cell lines, BG01 and BG02. By
      immunocytochemistry and reverse transcription polymerase chain reaction,
      undifferentiated cells expressed markers that are characteristic of ES cells,
      including SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, and OCT-3/4. Both cell lines were
      readily maintained in an undifferentiated state and could differentiate into
      cells of all three germ layers, as determined by expression of beta-tubulin III
      neuron-specific molecule (ectoderm), cardiac troponin I (cardiomyocytes,
      mesoderm), and alpha-fetoprotein (endoderm). A large-scale microarray (16,659
      genes) analysis identified 373 genes that were expressed at three-fold or higher
      levels in undifferentiated BG01 and BG02 cells as compared with pooled human RNA.
      Ninety-two of these genes were also highly expressed in four other hES lines
      (TE05, GE01, GE09, and pooled samples derived from GE01, GE09, and GE07).
      Included in the list are genes involved in cell signaling and development,
      metabolism, transcription regulation, and many hypothetical proteins. Two focused
      arrays designed to examine transcripts associated with stem cells and with the
      transforming growth factor-beta superfamily were employed to examine
      differentially expressed genes. Several growth factors, receptors, and components
      of signaling pathways that regulate embryonic development, in particular the
      nodal signaling pathway, were detected in both BG01 and BG02. These data provide
      a detailed characterization and an initial gene expression profile for the BG01
      and BG02 human ES cell lines.

PMID- 15153608
TI  - Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow
      derived mesenchymal stem cells.
AB  - The objective of this study was to examine the effects of cyclic compressive
      loading on chondrogenic differentiation of rabbit bone-marrow mesenchymal stem
      cells (BM-MSCs) in agarose cultures. Rabbit BM-MSCs were obtained from the tibias
      and femurs of New Zealand white rabbits. After the chondrogenic potential of BM
      MSCs was verified by pellet cultures, cell-agarose constructs were made by
      suspending BM-MSCs in 2% agarose (10(7) cells/ml) for a cyclic, unconfined
      compression test performed in a custom-made bioreactor. Specimens were divided
      into four groups: control; transforming growth factor (TGF-beta) (with TGF-beta1
      treatment); loading (with stimulation of cyclic, unconfined compressive loading);
      and TGF-beta loading (with TGF-beta1 treatment and loading stimulation) groups.
      In the loading experiment, specimens were subjected to sinusoidal loading with a
      10% strain magnitude at a frequency of 1 Hz for 4 hours a day. Experiments were
      conducted for 3, 7, and 14 consecutive days. While the experimental groups (TGF
      beta, loading, and TGF-beta loading) exhibited significantly higher levels of
      expressions of chondrogenic markers (collagen II and aggrecan) at three time
      periods, there were no differences among the experimental groups after an extra 5
      day culture. This suggests that compressive loading alone induces chondrogenic
      differentiation of rabbit BM-MSCs as effectively as TGF-beta or TGF-beta plus
      loading treatment. Moreover, both the compressive loading and the TGF-beta1
      treatment were found to promote the TGF-beta1 gene expression of rabbit BM-MSCs.
      These findings suggest that cyclic compressive loading can promote the
      chondrogenesis of rabbit BM-MSCs by inducing the synthesis of TGF-beta1, which
      can stimulate the BM-MSCs to differentiate into chondrocytes.

PMID- 15153609
TI  - Transfer and stable transgene expression of a mammalian artificial chromosome
      into bone marrow-derived human mesenchymal stem cells.
AB  - Mammalian artificial chromosomes (ACEs) transferred to autologous adult stem
      cells (SCs) provide a novel strategy for the ex vivo gene therapy of a variety of
      clinical indications. Unlike retroviral vectors, ACEs are stably maintained,
      autonomous, and nonintegrating. In this report we assessed the delivery
      efficiency of ACEs and evaluated the subsequent differentiation potential of ACE
      transfected bone marrow-derived human mesenchymal stem cells (hMSCs). For this,
      an ACE carrying multiple copies of the red fluorescent protein (RFP) reporter
      gene was transferred under optimized conditions into hMSCs using standard
      cationic transfection reagents. RFP expression was detectable in 11% of the cells
      4-5 days post-transfection. The RFP-expressing hMSCs were enriched by high-speed
      flow cytometry and maintained their potential to differentiate along adipogenic
      or osteogenic lineages. Fluorescent in situ hybridization and fluorescent
      microscopy demonstrated that the ACEs were stably maintained as single
      chromosomes and expressed the RFP transgenes in both differentiated cultures.
      These findings demonstrate the potential utility of ACEs for human adult SC ex
      vivo gene therapy.

PMID- 15153610
TI  - CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell
      subsets of hematopoietic and nonhematopoietic origin.
AB  - CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is
      expressed in metastatic colon and breast tumors as well as on the surface of
      hematopoietic stem cells. In this study, we used multiparameter flow cytometry
      and antibodies against CDCP1 to analyze the expression of CDCP1 on defined
      hematopoietic cell subsets of different sources. In addition, CDCP1 expression on
      leukemic blasts and on cells with nonhematopoietic stem/progenitor cell
      phenotypes was determined. Here we demonstrate that a subset of bone marrow (BM),
      cord blood (CB), and mobilized peripheral blood (PB) CD34+ cells expressed this
      marker and that CDCP1 was detected on CD34(+)CD38- BM stem/progenitor cells but
      not on mature PB cells. Analysis of leukemic blasts from patients with acute
      lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia in
      blast crisis revealed that CDCP1 is predominantly expressed on CD34(+)CD133+
      myeloid leukemic blasts. However, CDCP1 was not strictly correlated with CD34
      and/or CD133 expression, suggesting that CDCP1 is a novel marker for leukemia
      diagnosis. Stimulation of CD34+ BM cells with CDCP1-reactive monoclonal antibody
      CUB1 resulted in an increased (approximately twofold) formation of erythroid
      colony-forming units, indicating that CDCP1 plays an important role in early
      hematopoiesis. Finally, we show that CDCP1 is also expressed on cells
      phenotypically identical to mesenchymal stem/progenitor cells (MSCs) and neural
      progenitor cells (NPCs). In conclusion, CDCP1 is not only a novel marker for
      immature hematopoietic progenitor cell subsets but also unique in its property to
      recognize cells with phenotypes reminiscent of MSC and NPC.

PMID- 15153611
TI  - Enhancement of oligodendrocyte differentiation from murine embryonic stem cells
      by an activator of gp130 signaling.
AB  - Embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage
      embryos are a potential large scale source of oligodendrocytes and of their
      progenitors for transplantation into the central nervous system for the repair of
      demyelinating lesions. We found previously that interleukin-6 (IL-6) fused to its
      soluble receptor (IL-6R), a potent activator of the gp130 receptor, induces
      myelin gene expression in Schwann cells of embryonic dorsal root ganglia. Like
      leukemia inhibitory factor, IL-6R/IL-6 inhibits the differentiation of murine ES
      cells into embryoid bodies. In the present study, we show that this recombinant
      cytokine may be efficiently used to stimulate the differentiation of
      oligodendrocytes if added to ES cell-derived neural precursors. IL-6R/IL-6 leads
      to an increase in early chondroitin sulfate proteoglycan positive and late O4
      positive progenitors and to a stimulation of maturation into O1 and myelin basic
      protein expressing oligodendrocytes. Expression of the genes for transcription
      factor genes Olig-1 and Sox10, which appear early in the oligodendrocyte lineage,
      was stimulated by IL-6R/IL-6 addition. We conclude that this cytokine can
      significantly enhance the derivation of oligodendrocytes from ES cells.

PMID- 15153613
TI  - Derivation, characterization, and differentiation of human embryonic stem cells.
AB  - The derivation of human embryonic stem (hES) cells establishes a new avenue to
      approach many issues in human biology and medicine for the first time. To meet
      the increased demand for characterized hES cell lines, we present the derivation
      and characterization of six hES cell lines. In addition to the previously
      described immunosurgery procedure, we were able to propagate the inner cell mass
      and establish hES cell lines from pronase-treated and hatched blastocysts. The
      cell lines were extensively characterized by expression analysis of markers
      characteristic for undifferentiated and differentiated hES cells, karyotyping,
      telomerase activity measurement, and pluripotency assays in vitro and in vivo.
      Whereas three of the cell lines expressed all the characteristics of
      undifferentiated pluripotent hES cells, one cell line carried a chromosome 13
      trisomy while maintaining an undifferentiated pluripotent state, and two cell
      lines, one of which carried a triploid karyotype, exhibited limited pluripotency
      in vivo. Furthermore, we clonally derived one cell line, which could be
      propagated in an undifferentiated pluripotent state.

PMID- 15153612
TI  - Characterization of putative stem cell phenotype in human limbal epithelia.
AB  - This study evaluated proposed molecular markers related to stem cell (SC)
      properties with the intention of characterizing a putative SC phenotype in human
      limbal epithelia. Human corneal and limbal tissues were cut in the vertical and
      horizontal meridians for histology, transmission electron microscopy (TEM), and
      immunostaining. Semiquantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) and in situ hybridization were used to evaluate gene expression. TEM
      showed that the limbal basal cells were small primitive cells. Immunostaining
      disclosed that p63, ABCG2 and integrin alpha9 were primarily expressed by the
      basal epithelial cells of limbus. Antibodies against integrin beta1, epidermal
      growth factor receptor (EGFR), K19, enolase-alpha, and CD71 stained the basal
      cells of the limbus more brightly than the suprabasal epithelia. Integrin alpha6,
      nestin, E-cadherin and connexin 43 did not stain the limbal basal cells, but the
      suprabasal epithelia of the cornea and limbus showed strong immunoreactivity. K3
      and involucrin stained only corneal and limbal superficial cells. RT-PCR showed
      higher levels of p63, ABCG2 and integrin alpha9 mRNA, but lower levels of K3, K12
      and connexin 43 expressed in the limbal epithelia than the corneal epithelia. In
      situ hybridization showed that p63 transcripts were located in basal layer of the
      limbal epithelium. This work suggests that the basal epithelial cells of the
      limbus are p63, ABCG2 and integrin alpha9 positive, and nestin, E-cadherin,
      connexin 43, involucrin, K3, and K12 negative, with relatively higher expression
      of integrin beta1, EGFR, K19, and enolase-alpha. This putative SC phenotype may
      facilitate the identification and isolation of limbal epithelial SCs.

PMID- 15153615
TI  - Derivation of endothelial cells from CD34- umbilical cord blood.
AB  - CD34 is a transmembrane glycoprotein constitutively expressed on endothelial
      cells and hematopoietic stem cells. Use of CD34-recognizing antibodies has helped
      in the identification and isolation of CD34+ endothelial precursors from
      embryonic and adult tissues. However, CD34-null mice display no vascular
      abnormalities, demonstrating that CD34 antigen expression is not required for
      normal vascular development. Here we show that a CD34- cell population that
      includes endothelial cell precursors can be isolated from cord blood. In the
      presence of angiogenic factors, these cells mature to express the endothelial
      cell markers vascular endothelial-cadherin, vascular endothelial growth factor
      receptor-1 and -2, Tie-1 and -2 (tyrosine kinase with immunoglobulin and
      epidermal growth factor homology domains), von Willebrand factor, and CD31 while
      maintaining their CD34- status, and can be expanded in vitro for over 20
      passages. Moreover, in functional studies, these cells can undergo extracellular
      matrix-dependent morphogenic changes into capillary-like tubular structures. When
      transplanted into immunodeficient mice in conjunction with tumor cells or with
      the proangiogenic factor basic fibroblast growth factor, these cells can form
      functional microvessels arising along with host blood cells. These studies
      provide strong evidence for the existence of CD34- endothelial cell precursors in
      cord blood and suggest the use of ex vivo-expanded cord blood CD34- cells as a
      unique tool for the investigation of postnatal lineage diversification.

PMID- 15153614
TI  - Mesenchymal stem cells can be differentiated into endothelial cells in vitro.
AB  - Human bone marrow-derived mesenchymal stem cells (MSCs) have the potential to
      differentiate into mesenchymal tissues like osteocytes, chondrocytes, and
      adipocytes in vivo and in vitro. The aim of this study was to investigate the in
      vitro differentiation of MSCs into cells of the endothelial lineage. MSCs were
      generated out of mononuclear bone marrow cells from healthy donors separated by
      density gradient centrifugation. Cells were characterized by flow cytometry using
      a panel of monoclonal antibodies and were tested for their potential to
      differentiate along different mesenchymal lineages. Isolated MSCs were positive
      for the markers CD105, CD73, CD166, CD90, and CD44 and negative for typical
      hematopoietic and endothelial markers. They were able to differentiate into
      adipocytes and osteocytes after cultivation in respective media. Differentiation
      into endothelial-like cells was induced by cultivation of confluent cells in the
      presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor.
      Laser scanning cytometry analysis of the confluent cells in situ showed a strong
      increase of expression of endothelial-specific markers like KDR and FLT-1, and
      immunofluorescence analysis showed typical expression of the von Willebrand
      factor. The functional behavior of the differentiated cells was tested with an in
      vitro angiogenesis test kit where cells formed characteristic capillary-like
      structures. We could show the differentiation of expanded adult human MSCs into
      cells with phenotypic and functional features of endothelial cells. These
      predifferentiated cells provide new options for engineering of artificial tissues
      based on autologous MSCs and vascularized engineered tissues.

PMID- 15153616
TI  - Behavioral changes in unilaterally 6-hydroxy-dopamine lesioned rats after
      transplantation of differentiated mouse embryonic stem cells without
      morphological integration.
AB  - OBJECTIVE: Transplantation of fetal mesencephalic cells into the striatum has
      been performed in about 350 patients with Parkinson's disease and has been
      intensively studied in rat models of Parkinson's disease. Limited access to this
      material has shifted the focus toward embryonic stem (ES) cells. The grafting of
      undifferentiated ES cells to 6-hydroxy-dopamine (6-OHDA)-lesioned rats leads to
      behavioral improvements but may induce teratoma-like structures. This risk might
      be avoided by using more differentiated ES cells. In this study, we aimed to
      investigate differentiated mouse ES cells regarding their in vivo development and
      fate after transplantation in the striatum in the 6-OHDA rat model and the
      behavioral changes induced after transplantation. METHODS: Mouse ES cells were
      differentiated on PA6 feeder cells for 14 days before grafting. Twenty to twenty
      five percent of the neurons obtained were positive for tyrosine-hydroxylase (TH).
      PKH26-labeled cells were transplanted in the striata of unilaterally 6-OHDA
      lesioned rats. RESULTS: Direct PKH26 fluorescence visualization and TH staining
      proved the existence of cell deposits in the striata of all grafted animals,
      indicating cell survival for at least 5 weeks posttransplantation. There was no
      evidence of tumor formation. Immunocytochemical staining showed glial
      immunoreactivity surrounding the grafted cell deposits, probably inhibiting
      axonal outgrowth into the surrounding host tissue. There was a significant
      reduction in amphetamine-induced rotational behavior seen in grafted animals,
      which was not observed in sham-operated animals. CONCLUSIONS: The findings of
      this study suggest that the amphetamine-induced rotational behavioral test
      without histological confirmation is not proof of morphological integration with
      axonal outgrowth within the first 4 weeks posttransplantation.

PMID- 15153617
TI  - Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal
      stem cells suggests a role in cell mobilization, tissue repair, and wound
      healing.
AB  - Human mesenchymal stem cells (hMSC) are adult stem cells with multipotent
      capacities. The ability of mesenchymal stem cells to differentiate into many cell
      types, as well as their high ex vivo expansion potential, makes these cells an
      attractive therapeutic tool for cell transplantation and tissue engineering. hMSC
      are thought to contribute to tissue regeneration, but the signals governing their
      mobilization, diapedesis into the bloodstream, and migration into the target
      tissue are largely unknown. Here we report that hepatocyte growth factor (HGF)
      and the cognate receptor HGFR/c-met are expressed in hMSC, on both the RNA and
      the protein levels. The expression of HGF was downregulated by transforming
      growth factor beta. HGF stimulated chemotactic migration but not proliferation of
      hMSC. Therefore the HGF/c-met signaling system may have an important role in hMSC
      recruitment sites of tissue regeneration. The controlled regulation of HGF/c-met
      expression may be beneficial in tissue engineering and cell therapy employing
      hMSC.

PMID- 15153619
TI  - The molecular perspective: Cytochrome C and apoptosis.

PMID- 15153620
TI  - Sequencing strategies for parasite genomes.
AB  - Recent advances in the field of sequencing have enabled the determination of the
      complete nucleotide sequence of a large number of complex genomes. The complete
      genome sequence of the parasite Plasmodium falciparum has been published
      recently, and many other parasite genome initiatives are underway. Parasite
      genomes vary in size, nucleotide composition, polymorphism level, content, and
      distribution of repetitive elements. These genomic features affect the
      performance of sequencing strategies. As a consequence, each of the ongoing
      parasite genome projects has adopted distinct sequencing approaches. The degree
      of completeness and accuracy desired as well as available funds should be
      considered carefully when choosing the most appropriate sequencing strategy.

PMID- 15153618
TI  - Interactions of chemokines and chemokine receptors mediate the migration of
      mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve
      injury.
AB  - Mesenchymal stem cells (MSCs), cultured ex vivo, recently were shown to be able
      to migrate into sites of brain injuries when transplanted systemically or
      locally, suggesting that MSCs possess migratory capacity. However, the mechanisms
      underlying the migration of these cells remain unclear. In this study, we
      examined the role of some chemokines and their receptors in the trafficking of
      rat MSCs (rMSCs) in a rat model of left hypoglossal nerve injury. rMSCs
      transplanted into the lateral ventricles of the rat brain migrated to the avulsed
      hypoglossal nucleus, where the expression of chemokines, stromal-cell-derived
      factor 1 (SDF-1), and fractalkine was observed to be increased. This increase
      temporally paralleled the migration of rMSCs into the avulsed nucleus at 1 and 2
      weeks after operation. It has been found that rMSCs express CXCR4 and CX3CR1, the
      respective receptors for SDF-1 and fractalkine, and other chemokine receptors,
      CCR2 and CCR5. Furthermore, in vitro analysis revealed that recombinant human SDF
      1 alpha (rhSDF-1alpha) and recombinant rat fractalkine (rrfractalkine) induced
      the migration of rMSCs in a G-protein-dependent manner. Intracerebral injection
      of rhSDF-1alpha has also been shown to stimulate the homing of transplanted rMSCs
      to the site of injection in the brain. These data suggest that the interactions
      of fractalkine-CX3CR1 and SDF-1-CXCR4 could partially mediate the trafficking of
      transplanted rMSCs. This study provides an important insight into the
      understanding of the mechanisms governing the trafficking of transplanted rMSCs
      and also significantly expands the potential role of MSCs in cell therapy for
      brain injuries and diseases.

PMID- 15153621
TI  - Annotation of parasite genomes.
AB  - Genome annotation is the application of useful biological descriptions to
      sequence data. Different levels of time and effort can be invested to produce
      correspondingly different depths of annotation depending on what methods are
      employed. Researchers using genome data should, therefore, understand how
      annotations are generated to assess their validity correctly and to determine
      what level of inferences can be made accordingly. Thorough annotation requires a
      large range of procedures, most of which involve manual reviews of all available
      evidence. First, gene structures often are computed algorithmically and edited
      based on in-depth analyses of the underlying sequence data. Second, functional
      predictions draw on data from various sources. Finally, the use of structured and
      controlled descriptions, such as those provided by gene ontology, can be used so
      that final descriptions are not only consistent and unambiguous, but capable of
      being used in further downstream analyses such as cross-species comparisons.

PMID- 15153622
TI  - Parasite genome databases and web-based resources.
AB  - In the last decade, high-throughput genome sequencing and complementary
      techniques such as microarray and proteomics have generated, and will continue to
      generate, ever-increasing amounts of data. These technologies of gene discovery,
      expression, and functional analysis have been applied to a vast array of
      organisms, including parasites. In most instances, the data are freely available
      via the Internet, and researchers are becoming increasingly reliant on up-to
      date, centralized data repositories to complement wet bench science. This chapter
      presents an overview of resources relevant to researchers with an interest in
      para-site genomics and biology. After briefly touching on some of the publicly
      available nucleotide and protein sequence as well as domain databases, the focus
      turns to parasite genome projects and associated Web-based resources. A list of
      parasite sequencing projects current at the time of writing, including relevant
      Web site addresses, is provided. The available resources range from network sites
      and project pages at sequencing institutes to databases that integrate and curate
      sequence data and associated annotation with diverse biological datasets.
      Particular attention is given to three databases, GeneDB
      (http://www.genedb.org/), PlasmoDB (http://plasmodb. org/), and tigr db,
      detailing the scope of each database and the tools available for data querying
      and retrieval.

PMID- 15153623
TI  - Expressed sequence tags: medium-throughput protocols.
AB  - Generating expressed sequence tags is a simple, cheap, and efficient way to
      sample the genome of a target organism. An expressed sequence tag (EST) is a
      single-pass sequence derived from a single complementary DNA (cDNA) clone, and
      the sequence serves to identify the gene from which it derives. We present a set
      of tested laboratory protocols for setting up and performing an EST analysis of
      any chosen species. These medium-throughput protocols do not require dedicated
      genomics equipment, such as robots, and focus on the use of microtiter plates and
      multichannels. Using these protocols, a single competent research worker should
      be able to generate 2000 ESTs in 1 mo. In a nonnormalized library, these 2000
      ESTs should identify between 1000 and 1500 different genes, and thus possibly
      between 10 and 20% of the genes of any target parasite.

PMID- 15153624
TI  - Expressed sequence tags: analysis and annotation.
AB  - Expressed sequence tags (ESTs) present a special set of problems for
      bioinformatic analysis. They are partial and error-prone, and large datasets can
      have significant internal redundancy. To facilitate analysis of small EST
      datasets from in-house projects, we present an integrated "pipeline" of tools
      that take EST data from sequence trace to database submission. These tools also
      can be used to provide clustering of ESTs into putative genes and to annotate
      these genes with preliminary sequence similarity searches. The systems are
      written to use the public-domain LINUX environment and other openly available
      analytical tools.

PMID- 15153625
TI  - Positive selection scanning of parasite DNA sequences.
AB  - Parasites successfully exist within the host as a result of highly specific
      genetic adaptations. Therefore, detecting genes that contain relevant adaptive
      mutations can provide a guide to biological processes that are potentially
      essential to the parasite. Random genetic mutations that confer selective
      advantage can act to alter amino acids so as to confer gain of function that has
      positive impact on the survival of the parasite. Directional selection of
      advantageous mutations results from an elevated rate of nonsynonymous
      substitutions in rapidly evolving genes. Genes on which this positive selection
      operates are considered to have an evolutionary characteristic such that the
      normalized number of nonsynonymous (dn) substitutions is greater than that of
      synonymous (ds) substitutions. By searching in a statistically robust way for
      genes that contain this characteristic, it is possible to apply a stringent
      method to identify genes that may be under positive selection and thus to
      identify biological processes involving those genes that are essential to the
      survival of the parasite. Genes detected typically class into those under host
      immune surveillance and those intrinsic to pathways essential to survival of the
      parasite within the host. Depending on their function and location of protein
      expression, such genes have the potential to provide exceptional vaccine and drug
      candidates.

PMID- 15153626
TI  - RACE and RAGE cloning in parasitic microbial eukaryotes.
AB  - Many gene-cloning strategies and gene survey often provide partial sequence data.
      To exploit the information from these partial sequences numerous PCR-based
      approaches have been developed to clone full-length open reading frames. These
      approaches can be successful using small quantities of cDNA or genomic DNA as
      starting material and avoid the need to go through the complex and tedious
      process of constructing and screening gene libraries. Here we present two of
      these approaches, called RACE and RAGE, we used to successfully clone partial and
      full-length ORFs from amitochondriate parasitic microbial eukaryotes. The RACE
      approach uses cDNA as template for PCR cloning whereas RAGE uses genomic DNA.
      These two approaches were used to complement each other to provide full-length
      genes. The amitochondriate microbial eukaryotes we are investigating are of
      interest from both evolutionary and biomedical perspectives. We have investigated
      genes of mitochondrial origins in the obligate intracellular parasite called
      microsporidia. In these organisms spores are the only source of material that can
      be isolated from host cells and typically yield small amount of mRNA and genomic
      DNA for cloning. A full-length mitochondrial Hsp70 could be cloned and sequenced
      and specific antibody raised against a fusion protein. The highly specific
      antibody allowed us to demonstrate for the first time the presence of
      mitochondrial-like organelles in microsporidia.

PMID- 15153627
TI  - Amplified (restriction) fragment length polymorphism (AFLP) analysis.
AB  - The amplified (restriction) fragment length polymorphism (AFLP) technique is a
      method for DNA profiling that is now widely applied for assessing diversity among
      various organisms with varying genomic complexity, from small bacterial to large
      plant genomes. AFLP analysis combines the reliability of restriction enzyme
      digestion with the utility of the polymerase chain reaction. The technique can be
      applied to studies of DNA of any origin and complexity, without prior sequence
      knowledge. Therefore, it is very versatile and particularly valuable for
      organisms for which no substantive DNA sequence data are available. AFLP detects
      the presence of point mutations, insertions, deletions, and other genetic
      rearrangements. Typically, the fragments detected by AFLP are inherited in
      Mendelian fashion as co-dominant markers, making the technique amenable to
      tracking inheritance of genetic loci in progeny from crossed lines of organisms,
      and in studies of population genetics. This chapter describes the principles of
      AFLP and experimental procedures.

PMID- 15153628
TI  - Minisatellites and MVR-PCR for the individual identification of parasite
      isolates.
AB  - In recent years, a wide variety of biochemical and molecular typing systems have
      been employed in the study of parasite diversity aimed at investigating the level
      of genetic diversity and delineating the relationships among different species
      and subspecies. Parasite sequence-specific polymerase chain reaction (PCR)-based
      genotyping systems are among the most useful tools employed to date, because they
      can be applied to very small quantities of host-contaminated parasite material
      and, using repeated loci such as mini- and microsatellites, allow the
      identification and tracking of individual strains as well as the determination of
      allele and genotype frequencies in populations. Although minisatellites have been
      used very successfully to study parasite populations, in particular Trypanosoma
      brucei populations, there are some technical problems involved in the use of
      these markers. For example, minisatellite alleles tend to vary in a quasi
      continuous fashion, making unambiguous allele identification difficult. The
      development of minisatellite variant repeat (MVR) mapping by the polymerase chain
      reaction (MVR-PCR) as a digital approach to DNA typing has overcome many of the
      drawbacks of minisatellite length analysis. The system assays the dispersion
      patterns of MVRs within minisatellite alleles, producing an easily interpretable
      code for each allele. This technique not only allows unequivocal allele
      identification but also reveals cladistic information that can be used to
      determine the possible genetic relationships among the different strains and
      subspecies. The MVR mapping technique has been applied successfully to
      minisatellites in the parasite Plasmodium falciparum to uniquely identify
      strains, and more extensively in Trypansoma brucei, where it was used to
      determine population structure and to examine the relationships among T. brucei
      subspecies, providing evidence for multiple origins of human infectively. In this
      chapter, the methods for genotyping of T. brucei parasites using both
      minisatellite allele length and MVR mapping are described in full and can be
      easily adapted to apply to mini-satellites in other parasites.

PMID- 15153629
TI  - Analysis of differentially expressed parasite genes and proteins using
      transcriptomics and proteomics.
AB  - At any particular point in time, the full complement of transcribed RNAs and
      relevant proteins of a cell are known as the transcriptome and proteome,
      respectively. The composition of these two populations changes throughout the
      life cycle of a parasite or in response to environmental factors, such as drug
      treatments. Comparing the changes in the composition of the transcriptome and
      proteome between different life-cycle stages or in the same stage but under
      different conditions can be of particular interest, as it can allow the
      identification of potentially important differentially expressed genes and
      proteins. Combining the analysis of both the transcriptome and proteome in tandem
      allows changes in RNA transcripts to be followed right through to changes in the
      level of protein expression. The protocols in this chapter describe methods for
      analyzing the transcriptome, by using suppression subtraction hybridization to
      construct subtracted complementary DNA libraries, and the proteome, by using two
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These two
      methods are then integrated to allow the global changes in RNA and protein
      expression to be examined. The protocols have been adapted for working on
      parasites and contain extensive notes.

PMID- 15153630
TI  - Gene expression studies using self-fabricated parasite cDNA microarrays.
AB  - DNA microarray platforms represent a functional genomics technology that uses
      structured information obtained from genomic sequencing efforts as a means to
      study transcriptional processes in a systematic and high-throughput manner.
      Specifically in this chapter, we outline the ordered processes involved in large
      scale parasite gene expression studies including complementary (cDNA) microarray
      fabrication, total RNA isolation, cDNA labeling using fluorochromes, and DNA:DNA
      hybridization. Methods described herein were adapted for the study of schistosome
      sexual maturation and developmental biology but could be easily modified for the
      study of any additional parasitological system.

PMID- 15153631
TI  - DNA content analysis on microarrays.
AB  - The genome sequencing of protozoan parasites has facilitated the development of
      powerful postgenomics tools such as DNA microarrays and revolutionized the study
      of parasite biology. Large-scale genomic comparisons are useful in identifying
      the extent of genomic variability among related strains and isolates.
      Identification of deletions between geographically diverse clinical isolates is
      important in understanding parasite biology and the "fitness" of a given strain
      in dissemination. Additionally, the development of reliable diagnostic tests or
      identification of potential vaccine candidates is predicated on the large-scale
      conservation of the candidate genes. Parasites with variable virulence phenotypes
      (vaccine strain vs virulent strain) can also be studied for their genomic
      variability and provide further insights into the potential role of genotypic
      variability and its relationship to virulence. This chapter outlines the
      utilization of DNA microarrays to study genomic content.

PMID- 15153632
TI  - Typing single-nucleotide polymorphisms in Toxoplasma gondii by allele-specific
      primer extension and microarray detection.
AB  - Genotyping is an important tool for epidemiological and population genetic
      studies in protozoan parasites. The most commonly used method for genotyping is
      polymerase chain reaction (PCR)-based restriction fragment length polymorphism
      (RFLP) analysis of single nucleotide polymorphisms (SNPs). However, PCR-RFLP
      analysis is labor intensive, and only a proportion of the SNPs are recognized by
      currently available restriction enzymes. Here, we have developed a more efficient
      microarray-based method to genotype SNPs in the protozoan parasite Toxoplasma
      gondii. This method is sensitive, accurate, and capable of analyzing multiple
      SNPs simultaneously in a high-throughput format.

PMID- 15153633
TI  - Transfection of the human malaria parasite Plasmodium falciparum.
AB  - Methods to transiently and stably transfect blood stages of the human malaria
      parasite Plasmodium falciparum have been developed and adapted for gene-knockout,
      allelic replacement, and transgene expression in this organism. These methods are
      detailed in this chapter, as are approaches used to monitor transfectants during
      the selection process. The different plasmid vectors that are currently used for
      gene targeting and transgene expression (including green fluorescent protein
      expression) are also described.

PMID- 15153634
TI  - A PCR-based method for gene deletion and protein tagging in Trypanosoma brucei.
AB  - Sequence information on the Trypanosoma brucei genome is rapidly accumulating. As
      a consequence, there is a need for techniques to analyze gene function
      systematically. Here, we describe a polymerase chain reaction (PCR)-based method
      for direct gene deletion and the generation of epitope-tagged fusion proteins.
      The approach is based on methodologies developed for Saccharomyces cerevisiae and
      involves PCR amplification of a reporter cassette using primers containing
      flanking sequences specific to the target gene. The PCR product is then
      transfected directly into procyclic T. brucei cells, and homologous recombinants
      that carry the deleted or tagged target gene are identified.

PMID- 15153635
TI  - Analysis of gene function in Trypanosoma brucei using RNA interference.
AB  - Trypanosoma brucei, a flagellate protozoa of the family Trypanosomatidae, has
      become one of the model systems for unicellular pathogens to study fundamentally
      important biological phenomena. The method of choice today to examine gene
      function in these organisms is RNA interference (RNAi). Messenger RNA (mRNA)
      degradation is triggered by double-stranded RNA (dsRNA) produced in vivo from
      transgenes transcribed from opposing tetracycline (tet)-inducible T7 RNA
      polymerase promoters, or hairpin RNA transcribed from the tet-inducible procyclic
      acidic repetitive protein promoter. This chapter describes some of the methods we
      employ for ablation of gene expression by RNAi in T. brucei with particular
      emphasis on transfection and cloning of procyclic cells, induction of dsRNA
      expression, isolation of RNA, and analysis of dsRNA and target mRNA.

PMID- 15153636
TI  - In vitro shuttle mutagenesis using engineered mariner transposons.
AB  - Advances in our understanding of the protozoan parasite Leishmania have been
      facilitated by the development of molecular and genetic tools. One powerful
      approach for gene identification and analysis is transposon mutagenesis. This can
      be performed directly in vivo, but often it is more convenient to generate
      transpositions in vitro for subsequent analysis in vivo, in a process termed
      "shuttle mutagenesis." The Drosophila element mariner is well suited for
      application by either route. Minimal mariner elements containing cis-acting
      elements required for transposition have been generated, which can be further
      modified to suit the needs of the experimenter. Additional genetic markers and/or
      reporters can be introduced, which are useful for procedures such as insertional
      mutagenesis, shotgun sequencing, or the generation of protein and transcriptional
      fusions for subsequent analysis. Active transposase can readily be generated
      following expression in Escherichia coli, and efficiencies of 10-3/target can be
      obtained, allow-ing the generation of large transposon insertion libraries
      suitable for subsequent screening in vivo. This chapter explains the steps
      necessary to purify active Mos1 transposase and conduct an in vitro transposition
      reaction. We also discuss some of the considerations relevant to the design and
      application of functional mariner elements (donor plasmids) relevant to studies
      in Leishmania and other organisms.

PMID- 15153637
TI  - Random mutagenesis strategies for construction of large and diverse clone
      libraries of mutated DNA fragments.
AB  - The first important step toward a successful preparation of large and diverse DNA
      libraries with desired complexity is to select a suitable mutagenesis strategy.
      This chapter describes three different methods for random mutagenesis, the use of
      XL1-red cells, error-prone polymerase chain reaction (PCR), and degenerate
      oligonucleotides-Pfu (DOP). These mutagenesis strategies possess different
      benefits and pitfalls; thus, they are differentially useful for production of DNA
      libraries with different density and complexity. The use of XL1-red, an
      engineered Escherichia coli with DNA repair deficiency, is one of the simplest
      mutagenesis and requires no subcloning step. After plasmid encoding DNA of inter
      est is transformed into the cells, the mutations are simply generated during each
      round of DNA replication. The mutation frequency of this method is reported to be
      1 base change per 2000 nucleotides; however, it can be slightly increased by
      extending the culture period to allow the accumulation of more mutations. This
      strategy is suitable for generation of random mutations with low frequency in a
      large target DNA. Error-prone PCR is one of the most widely used random
      mutagenesis. During DNA amplification, misincorporation of nucleotides can be
      promoted by altering the nucleotide ratio and the concentration of divalent
      cations in the reaction. We discovered that, by adjusting template concentration,
      frequency of mutation could be controlled easily and a library with desired
      mutation rate could be obtained. Additionally, efficiency of subsequent cloning
      steps to insert the PCR product into plasmid DNA is also a key factor determining
      size and complexity of the libraries. DOP mutagenesis is a rapid and effective
      method for random mutagenesis of small DNA and peptides. This strategy uses two
      chemically synthesized degenerate oligonucleotides as primers. By controlling the
      positions and ratios of degenerate nucleotides used during oligonucleotide
      synthesis, it is possible to control both the position and rate of mutation in
      degenerated region of the primers. The primers are integrated into newly
      synthesized plasmid DNA by primer extension reaction using Pfu DNA polymerase.
      After plasmid DNA template encoding wild-type sequence is eliminated from the
      reaction by DpnI digestion, the pool of mutagenized plasmids can then be used
      directly in screening procedures.

PMID- 15153638
TI  - Separation, digestion, and cloning of intact parasite chromosomes embedded in
      agarose.
AB  - The chromosomes of most protozoan parasites cannot be visualized using
      conventional microscopy because they are too small and do not condense
      sufficiently at metaphase. Therefore, the development of pulsed field gel
      electrophoresis allowed the resolution of many parasite karyotypes for the first
      time. The ability to prepare intact chromosomes in agarose plugs and to isolate
      individual homologs by electrophoresis has led to many new applications in
      parasite genomic analysis. This chapter describes the preparation of chromosome
      plugs from single-celled protozoan parasites, providing numerous tips on how to
      achieve the highest-quality preparations that will last for years. We also
      provide detailed protocols for the manipulation of individual excised
      chromosomes, including restriction mapping and preparation of chromosome shotgun
      libraries as used in many of the genomic sequencing projects. The protocols
      provided here underpin several of the advanced methods of genomic analysis and
      manipulation described in this volume of parasite genomics protocols.

PMID- 15153639
TI  - Chromosome fragmentation in leishmania.
AB  - Chromosome fragmentation (CF) constitutes one means of manipulating eukaryotic
      genomes and provides a powerful tool for examining both the structure and
      function of chromosomes. During the past 15 yr, CF, which is based on the use of
      transfection, has been widely used in yeast and mammals to elucidate the
      functional elements required for normal chromosome maintenance. However, in view
      of the relatively late development of parasite genome projects, this strategy has
      only been used recently in parasites. Here, we describe basic methods for CF
      (except telomere-mediated fragmentation) experiments and analysis in Leishmania.
      Current limitations of this methodology are precisely the lack of knowledge of
      the nature of centromeres and autonomously replicating sequences in this and
      other protozoa, the poor understanding of precise recombination mechanisms, as
      well as the fact that the deletion of unknown genes essential to parasite
      survival may interfere with recombination events and chromosomal rearrangements.
      Still, this powerful method has enriched our basic knowledge of chromosomal
      structure and maintenance.

PMID- 15153640
TI  - FISH mapping for helminth genome.
AB  - Basic techniques for fluorescence in situ hybridization (FISH) mapping that have
      been used in genome projects on schistosomes and filariae are introduced. The
      chapter shows techniques specific for bacterial artificial chromosome (BAC) and
      yeast artificial chromosome (YAC) clones and includes experiences of chromosome
      preparation, DNA labeling, hybridization, microscopy, and localization of BAC
      clones.

PMID- 15153641
TI  - Fiber-FISH: fluorescence in situ hybridization on stretched DNA.
AB  - High-resolution fluorescence in situ hybridization (FISH) on deproteinized,
      stretched DNA prepared by in situ extraction of whole cells immobilized on
      microscope glass slides allows the visualization of individual genes or other
      small DNA elements on chromosomes with a resolution of approx 1000 bp.
      Applications of fiber-FISH range from the determination of numbers of repetitive
      genes to establishing the physical order of cloned DNA fragments along continuous
      sections of individual chromosomes. Particularly in organisms with relatively
      small and gene dense genomes, such as protozoan parasites, fiber-FISH can easily
      be used as a complementary technique to classical in vitro mapping approaches.

PMID- 15153642
TI  - Yeast two-hybrid assay for studying protein-protein interactions.
AB  - Protein-protein interactions occur in a wide variety of biological processes and
      essentially control the cell fate from division to death. Today, the
      identification of proteins that interact with a protein of interest is a focus of
      intensive research and is an essential element of the rapidly growing field of
      proteomics. Yeast two-hybrid assays represent a versatile tool to study protein
      interactions in vivo. GAL4-based assay, for example, uses yeast transcription
      factor GAL4 for detection of protein interactions by transcriptional activation.
      Some transcription factors (such as GAL4) possess a characteristic phenomenon
      that the transactivation function can be restored when the factor's DNA-binding
      domain (DBD) and its transcription-activation domain (AD) are brought together by
      two interacting, heterologous proteins. GAL4-yeast two-hybrid assay uses two
      expression vectors, one uses GAL4-DBD and the other uses GAL4-AD. DNA sequences
      encoding the two proteins of interest (or a protein and a complementary DNA
      library) can be cloned in the GAL4-DBD and GAL4-AD vectors to form the bait and
      the target of the interaction trap, respectively. A selection of host cells with
      different reporter genes and different growth selection markers provides a means
      to detect and confirm protein-protein interactions and highlight the flexibility
      of these assays to fit different applications. This chapter presents an outline
      for the GAL4-based yeast two-hybrid system with a detailed description of the
      vectors, host cells, and methods for detection and verifying protein
      interactions.

PMID- 15153644
TI  - Perspective in progress of cardiovascular gene therapy.
AB  - Recent progress in molecular and cellular biology has developed numerous
      effective cardiovascular drugs. However, there are still a number of diseases for
      which no known effective therapy exists, such as peripheral arterial disease,
      ischemic heart disease, restenosis after angioplasty, vascular bypass graft
      occlusion, and transplant coronary vasculopathy. Currently, gene therapy is
      emerging as a potential strategy for the treatment of cardiovascular disease to
      treat such diseases despite of its limitations. The first human trial in
      cardiovascular disease was started in 1994 to treat peripheral vascular disease
      using vascular endothelial growth factor (VEGF). Since then, many different
      potent angiogenic growth factors have been tested in clinical trials to treat
      peripheral arterial disease. The results from these clinical trials seem to
      exceed expectations. Improvement of clinical symptoms in peripheral arterial
      disease and ischemic heart disease has been reported. In addition, another
      strategy for combating disease processes, the targeting of transcriptional
      processes, has been tested in a human trial. Genetically modified vein grafts
      transfected with decoy against E2F, an essential transcription factor in cell
      cycle progression, revealed apparent long-term potency in human patients. This
      review focuses on the future potential of gene therapy for the treatment of
      cardiovascular disease.

PMID- 15153643
TI  - From genomes to vaccines for leishmaniasis.
AB  - A total of 2183 clones derived from four life cycle stage-specific, spliced
      leader cDNA libraries of Leishmania major LV39 Neal strain were randomly picked
      and sequenced to generate expressed sequence tags (ESTs). Then 1094 unique genes
      were identified, with 18.2% having BLAST hits with known genes/proteins and 81.8%
      failing to match genes currently deposited in public databases. Approximately 250
      unique genes were obtained from a lesion-derived amastigote complementary DNA
      (cDNA) library, the form of the parasite that is infective to the mammalian host.
      Polymerase chain reaction (PCR)-amplified ESTs were spotted onto glass slides,
      and DNA microarray used to identify a further approx 100 unique cDNAs highly
      expressed in amastigotes. One hundred unique, randomly selected amastigote
      expressed genes were PCR amplified to exclude the 5'-spliced leader, and the full
      length genes subcloned into the TOPO-TA cloning vector. The genes were sequence
      verified, excised using restriction enzyme digestion, and cloned upstream of the
      eukaryotic cytomegalovirus promoter into the expression vector pcDNA3. Expression
      plasmids were sequence-verified and large-scale, endotoxin-free plasmids
      prepared. Then 100 microg of each expression plasmid (DNA vaccine) was delivered
      subcutaneously to the rump of susceptible BALB/c mice, the mice boosted 4 wk
      later and then challenged 2 wk post-boost with 2 x 10(6) L. major LV39 parasites
      to the hind footpad. Infection was monitored on a weekly basis by measuring
      footpad depth with digital calipers. Protection was scored by comparing the
      footpad depth of mice receiving empty vector DNA to those immunized with DNA
      containing L. major amastigote-expressed genes.

PMID- 15153645
TI  - A new paradigm for diabetes and obesity: the hepatic insulin sensitizing
      substance (HISS) hypothesis.
AB  - The glucose disposal effect of insulin after a meal is accounted for in
      approximately equal measure by the direct action of insulin and the action of
      HISS (hepatic insulin sensitizing substance) released from the liver and acting
      on skeletal muscle to stimulate glucose storage as glycogen. The ability of
      insulin to cause HISS release is determined by hepatic parasympathetic nerves.
      Eliminating the parasympathetic signal by surgical denervation of the liver or by
      blockade of hepatic muscarinic receptors, hepatic nitric oxide synthase, or
      hepatic cyclooxygenase results in insulin resistance that can be accounted for by
      the absence of HISS action and is referred to as HISS-dependent insulin
      resistance (HDIR). Animal models in which the insulin resistance has been shown
      to be HDIR includes the spontaneously hypertensive rat, sucrose fed rats, animals
      with liver disease, adult offspring of fetal alcohol exposure, acute stress, and
      ageing. We suggest that HDIR accounts for the major metabolic disturbances in
      type 2 diabetes, including the postprandial hyperglycemia that results in the
      majority of pathologies related to diabetes. The observation of meal-induced
      insulin sensitization (MIS) and the role of HISS allows for consideration of a
      new paradigm relating meal processing, diabetes, obesity, and insulin resistance.
      New diagnostic approaches and therapeutic targets are described.

PMID- 15153646
TI  - Doxorubicine-congestive heart failure-increased big endothelin-1 plasma
      concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide
      BPC157 in rat and mouse.
AB  - Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI
      mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and
      then a 4-week-rest period) is consistently deteriorating throughout next 14 days,
      if not reversed or ameliorated by therapy (/kg per day): a stable gastric
      pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for
      inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng),
      losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once
      daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1)
      and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of
      therapy and clinical status (hypotension, increased heart rate and respiratory
      rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once
      daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited
      additionally increased BET-1 and aggravated clinical status, while enzyme values
      maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment
      reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH
      (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1
      (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10
      ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is
      accordingly improved by the BPC157 regimens and amlodipine.

PMID- 15153648
TI  - Alpha-mangostin induces Ca2+-ATPase-dependent apoptosis via mitochondrial pathway
      in PC12 cells.
AB  - We investigated the cell death effects of eight xanthones on PC12 rat
      pheochromocytoma cells. Among these compounds, alpha-mangostin, from the fruit
      hull of Garcinia mangostana L., had the most potent effect with the EC(50) value
      of 4 microM. Alpha-mangostin-treated PC12 cells demonstrated typical apoptotic
      DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow
      cytometric analysis indicated that this compound induced apoptosis in time-and
      concentration-dependent manners. Alpha-mangostin showed the features of the
      mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and
      cytochrome c release. Furthermore, alpha-mangostin inhibited the
      sarco(endo)plasmic reticulum Ca(2+)-ATPase markedly. There was a correlation
      between the Ca(2+)-ATPase inhibitory effects and the apoptotic effects of the
      xanthone derivatives. On the other hand, c-Jun NH(2)-terminal kinase (JNK/SAPK),
      one of the signaling molecules of endoplasmic reticulum (ER) stress, was
      activated with alpha-mangostin treatment. These results suggest that alpha
      mangostin inhibits Ca(2+)-ATPase to cause apoptosis through the mitochondrial
      pathway.

PMID- 15153647
TI  - The effects of K+ channels modulators terikalant and glibenclamide on membrane
      potential changes induced by hypotonic challenge of guinea pig ventricular
      myocytes.
AB  - Contribution of inward rectifier K(+) currents (I(K1)) and ATP-sensitive K(+)
      currents (I(KATP)) to membrane potential changes of ventricular myocytes
      appearing during hypotonic challenge is unclear. We used here the whole cell
      patch clamp technique, voltage and current clamp modes, to record membrane
      potentials and ionic currents in isolated guinea pig ventricular myocytes under
      isotonic or hypotonic perfusion. The difference in osmolarity between iso- and
      hypotonic solutions was about 100 mOsm. Exposure to hypotonic solution for 60 s
      induced initial prolongation of action potential duration at 90% of
      repolarization (APD(90)) (from 176 +/- 10 to 189 +/- 11 ms, P<0.05, n = 13).
      Further perfusion for the next 300 s shorthened APD(90) to 135 +/- 9 ms (P<0.01,
      in comparison with control values, n = 13) and depolarized resting potential from
      -79.2 +/- 1.5 to -75.0 +/- 0.9 mV, (P<0.05, n = 13). Neither pretreatment with a
      blocker of I(K1) channels, terikalant at 10 microM, nor with a blocker of I(KATP)
      channels, glibenclamide at 1 microM, prevented the above-mentioned changes in
      membrane potential induced by hypotonic challenge when a pipette solution
      containing 5 mM ATP was used. Also, glibenclamide and terikalant did not affect
      the hypotonic-sensitive current, obtained by ramp or voltage-step protocols,
      respectively. Additionally, the current-voltage relationship (I-V curve) of the
      whole cell hypotonic-sensitive current shifted from an isotonic I-V curve in a
      parallel way. Our results indicate that I(K1) and I(KATP) do not participate in
      membrane potential changes induced by hypotonic solution at least in the guinea
      pig ventricular myocytes with sufficient intracellular ATP.

PMID- 15153649
TI  - Ephedrae herba in Mao-Bushi-Saishin-To inhibits IgE-mediated histamine release
      and increases cAMP content in RBL-2H3 cells.
AB  - Acute effect of Mao-Bushi-Saishin-To (Ma-Huang-Fu-Zi-Xi-Xin-Tang in Chinese: MBS)
      on histamine release was investigated. The IgE-mediated anaphylaxic response in
      Wistar rats was significantly suppressed by MBS and Mao. However, Saishin and
      Bushi had no or little effect on the antigen-mediated anaphylaxic reaction. Mao
      as well as MBS but not Saishin nor Bushi inhibited IgE-mediated histamine release
      from rat basophilic leukemia (RBL-2H3) cells. Consistently, MBS and Mao but not
      Bushi nor Saishin increased cAMP levels in RBL-2H3 cells. However, ephedrine,
      methylephedrine, and pseudoephedrine, the main components in Mao, did not affect
      histamine release. From these results, increase of cAMP levels may account for
      the inhibitory effect of Mao on histamine release. Furthermore, these inhibitory
      actions of MBS were mainly due to Mao with an ingredient(s) different from
      ephedrines.

PMID- 15153650
TI  - Effects of nonpeptide and selective V1 and V2 antagonists on blood pressure short
      term variability in spontaneously hypertensive rats.
AB  - Effects of V(1) (OPC-21268) and V(2) (OPC-31260) vasopressin antagonists on blood
      pressure (BP) short-term variability were investigated in adult spontaneously
      hypertensive rats (SHR) under basal conditions and after the stimulation of
      vasopressin release by hemorrhage. BP was recorded intra-arterially and sampled
      at 20 Hz to be analyzed on a personal computer. BP time spectra were calculated
      on 30 stationary overlapping 2048 point-time series. Spectral power was estimated
      in total (0.00976 - 3 Hz), very low frequency (VLF: 0.00976 - 0.195 Hz), low
      frequency (LF: 0.195 - 0.605 Hz), and high frequency (HF: 0.8 - 3 Hz) regions.
      Under basal conditions a V(1) antagonist (5 mg/kg, i.v.) decreased BP without
      affecting BP variability, while combined (V(1) + V(2)) blockade or V(2) blockade
      (1 mg/kg, i.v.) alone did not affect cardiovascular parameters. Mild hemorrhage
      (5 ml/kg per min) increased HF-BP variability, while moderate (10 ml/kg per min)
      and massive (15 ml/kg per min) hemorrhage did not affect it. In V(1), but not
      V(2), antagonist pre-treated SHR HF-BP increased significantly after moderate and
      massive hemorrhage. V(1) or V(2) antagonist pre-treatment also enhanced VLF-BP
      variability during massive hemorrhage. Moreover V(1) blockade prevented
      hemorrhage-induced bradycardia, while V(2) blockade potentiated it. It follows
      that in adult SHR, vasopressin buffers BP oscillations in HF and VLF frequency
      domains only in hypovolaemic conditions and that the modulation of the autonomic
      adjustment of the HR to hemorrhage by vasopressin is preserved.

PMID- 15153651
TI  - Aminoguanidine protects against intracranial hypertension and cerebral ischemic
      injury in experimental heatstroke.
AB  - The aim of the present study was to ascertain whether aminoguanidine attenuated
      intracranial hypertension and cerebral ischemic injury in experimental
      heatstroke. Urethane-anesthetized rats were exposed to heat stress (ambient
      temperature of 43 degrees C) to induce heatstroke. Control rats were exposed to
      24 degrees C. Mean arterial pressure, cerebral perfusion pressure, and cerebral
      blood flow after the onset of heatstroke were all significantly lower than in
      control rats. However, colonic temperature, intracranial pressure, heart rate,
      cerebral inducible nitric oxide synthase (iNOS)-dependent NO, and neuronal damage
      score were greater after the onset of heatstroke. Aminoguanidine (30 micromol/kg,
      i.v.; 30 min before the start of heat exposure) pretreatment significantly
      attenuated the heatstroke-induced hyperthermia, arterial hypotension,
      intracranial hypertension, cerebral ischemia and neuronal damage, and increased
      iNOS-dependent NO formation in the brain. The extracellular concentrations of
      ischemic (e.g., glutamate and lactate/pyruvate ratio) and damage (e.g., glycerol)
      markers in the hypothalamus were also increased after the onset of heatstroke.
      Aminoguanidine pretreatment significantly attenuated the increase in hypothalamic
      ischemia and damage markers associated with heatstroke. Delaying onset of
      aminoguanidine administration (i.e., 0 or 30 min after the start of heat
      exposure) reduced the preventive efficiency on heatstroke-induced hyperthermia,
      arterial hypotension, intracranial hypertension, cerebral ischemia, and increased
      iNOS-dependent NO formation in brain. These results suggest that aminoguanidine
      protects against heatstroke-induced intracranial hypertension and cerebral
      ischemic injury by inhibition of cerebral iNOS-dependent NO production.

PMID- 15153652
TI  - CD14 glycoprotein expressed in vascular smooth muscle cells.
AB  - The inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle
      cells is an important factor for pathogenesis of septic shock or multiple organ
      dysfunction syndrome. The mechanisms of iNOS expression in such conditions are
      partly known. This study tried to clarify the signal transduction of
      lipopolysaccharide (LPS) single stimulation that induces iNOS mRNA and protein in
      vascular smooth muscle cells (VSMC). VSMC were primarily cultured from rat aorta.
      The concentrations of nitrite in culture media were measured by the Griess
      reaction. Western blottings and immunoreaction for iNOS, nuclear factor kappaB
      (NFkappaB) p65, and CD14 protein were performed. mRNAs of iNOS and tumor necrosis
      factor (TNF) alpha were analyzed by RT-PCR. Genistein inhibited LPS induced early
      phase nitrite production, while pyrrolidine dithiocarbamate (PDTC) inhibited
      nitrite production at a late phase. PDTC significantly reduced NFkappaB p65 and
      iNOS protein expression by LPS. TNFalpha mRNA expression by LPS was not detected
      in VSMC. Membranous CD14 glycoprotein was detected in VSMC and soluble CD14
      glycoprotein was not detected in fetal bovine serum added in culture media. These
      results suggest that CD14 glycoprotein is present on the cell membranes of VSMC,
      a non-myelomonocyte lineage, acting as an LPS receptor. Activations of tyrosine
      kinase and NFkappaB p65 are essential for iNOS expression by LPS single
      stimulation, while TNFalpha is not a concern to iNOS expression in VSMC.

PMID- 15153653
TI  - Essential role of the interstitial cells of Cajal in nitric oxide-mediated
      relaxation of longitudinal muscle of the mouse ileum.
AB  - The role of interstitial cells of Cajal (ICC) in electrical field stimulation
      (EFS)-induced neurogenic responses in ileum was studied by using the ICC
      deficient mutant (SLC-W/W(V)) mouse and its wild type. In the immunohistochemical
      study with anti-c-Kit antibody, ICC was observed in the myenteric plexus (MY) and
      deep muscular plexus (DMP) region in the wild type. In the mutant, ICC-MY were
      lost, only ICC-DMP were present. EFS induced a rapid contraction of the ileal
      segments from the wild type mouse in the direction of longitudinal muscle. In the
      mutant mouse, onset of contraction was delayed and its rate was slowed. EFS
      induced nonadrenergic, noncholinergic (NANC) relaxation in the presence of
      atropine and guanethidine in the wild type. A nitric oxide synthase inhibitor
      inhibited the relaxation and L-arginine reversed it. In the mutant, EFS did not
      induce NANC relaxation. There was no difference between the responsiveness of the
      segments from wild type and mutant mice to exogenously added acetylcholine or Nor
      1. Taking into account the selective loss of ICC-MY in the mutant mice, it seems
      likely that ICC-MY have an essential role in inducing nitric oxide-mediated
      relaxation of longitudinal muscle of the mouse ileum and that ICC-MY partly
      participate in EFS-induced contraction.

PMID- 15153654
TI  - Identification of endogenous surrogate ligands for human P2Y receptors through an
      in silico search.
AB  - G protein-coupled receptors (GPCRs) are distributed widely throughout the human
      body, and nearly 50% of current medicines act on a GPCR. GPCRs are considered to
      consist of seven transmembrane alpha-helices that form an alpha-helical bundle in
      which agonists and antagonists bind. A 3D structure of the target GPCR is
      indispensable for designing novel medicines acting on a GPCR. We have previously
      constructed the 3D structure of human P2Y(1) (hP2Y(1)) receptor, a GPCR, by
      homology modeling with the 3D structure of bovine rhodopsin as a template. In the
      present study, we have employed an in silico screening for compounds that could
      bind to the hP2Y(1)-receptor model using AutoDock 3.0. We selected 21 of the 30
      top-ranked compounds, and by measuring intracellular Ca(2+) concentration, we
      identified 12 compounds that activated or blocked the hP2Y(1) receptor stably
      expressed in recombinant CHO cells. 5-Phosphoribosyl-1-pyrophosphate (PRPP) was
      found to activate the hP2Y(1) receptor with a low ED(50) value of 15 nM. The
      Ca(2+) assays showed it had no significant effect on P2Y(2), P2Y(6), or P2X(2)
      receptors, but acted as a weak agonist on the P2Y(12) receptor. This is the first
      study to rationally identify surrogate ligands for the P2Y-receptor family.

PMID- 15153655
TI  - Noxious stimuli evoke a biphasic flexor reflex composed of A delta-fiber-mediated
      short-latency and C-fiber-mediated long-latency withdrawal movements in mice.
AB  - The nociceptive flexor reflex was studied in mice, focusing in particular on
      movement. Electrical stimuli delivered to the ventral aspect of the toe through a
      pair of needle electrodes inserted subcutaneously elicited a biphasic withdrawal
      reflex that was composed of short- and long-latency movements of the ipsilateral
      hind paw. The first response had a lower activation threshold compared with the
      second movement. Similar biphasic responses were observed in the afferent volley
      recorded from the sciatic nerve as well as in the electromyographic activity
      recorded from the femoris biceps muscle. Tetrodotoxin, applied over the sciatic
      nerve, abolished the first movement, but the second response was preserved,
      revealing that the first movement was elicited by the activation of myelinated
      Adelta-fibers, whereas the second movement was mediated by unmyelinated C-fibers.
      Thus, simultaneous activation of Adelta- and C-fibers leads to separate, but
      sequentially occurring withdrawal movements of the hind paw in mice. Systemic
      administration of morphine suppressed the withdrawal reflex, which was
      attributable to a preferential reduction of the Adelta-fiber-mediated short
      latency component. This method will be useful for understanding how Adelta-fiber-
      and C-fiber-mediated nociceptive reflexes are affected by drugs in the whole
      animal system.

PMID- 15153656
TI  - Mechanism of action by which aspirin alleviates detrusor hyperactivity in rats.
AB  - We examined the effect of aspirin on urodynamic parameters in normal and
      cyclophosphamide-induced cystitic rats and compared them in rats with or without
      sensory denervation. Cystometry was performed under urethane anesthesia; and
      volume threshold for micturition (VT), micturition frequency (MF), micturition
      pressure (MP), and micturition volume (MV) were determined. Cystitis was induced
      by pretreatment with cyclophosphamide and sensory denervation was performed by
      pretreating animals with a large dose of capsaicin. PGE(2) and 6-keto-PGF(1alpha)
      contents in the bladder were determined by ELISA. Sensory intact, cystitic rats
      showed decrement of VT and increment of MF. Aspirin increased VT and decreased MF
      in the cystitic condition. Both PGE(2) and 6-keto-PGF(1alpha) contents in the
      bladder were significantly increased in cystitic rats, but such increases were
      completely inhibited by aspirin. In sensory denervated rats, aspirin showed a
      marginal tendency of increment of VT. Cystitic rats showed overflow micturition
      in the sensory denervated condition, but VT was the same as that of normal rats.
      Furthermore, following capsaicin pretreatment, aspirin had no effect on the
      cystometrogram in cystitic rats. From these findings, it is concluded that
      suppression of sensory C-fiber via inhibition of PGs synthesis in the bladder is
      involved in the pharmacological action of aspirin in the detrusor hyperactivity.

PMID- 15153658
TI  - Characterization of intrinsic sympathomimetic activity of carteolol in rat
      cardiovascular preparations.
AB  - We evaluated in vitro, in myocardial and vascular preparations isolated from
      reserpine-treated rats, the intrinsic sympathomimetic activity (ISA) of
      carteolol, a beta(1)/beta(2)-adrenoceptor blocking agent used in cardiovascular
      and non-cardiovascular diseases. In spontaneously beating atria, carteolol, at
      low concentrations (0.01 and 0.1 microM), antagonized the positive inotropic
      effect of isoprenaline, whereas at higher concentrations (1 microM to 1 mM), it
      caused an increase in the force of contraction (EC(50): 4.6 +/- 0.1 microM,
      E(max): 17.1 +/- 1.1%, with respect to the maximum isoprenaline response) and a
      slight increase (7.8 +/- 1.9% over basal values) in the heart rate. The positive
      inotropic effect of carteolol was abolished by concentrations of propranolol or
      timolol (10 microM) much higher than those blocking isoprenaline effects in the
      same preparations. A similar positive inotropic effect was also observed in
      electrically driven left atrium and in Langendorff perfused hearts. Functional
      and biochemical evidences supported the involvement of cAMP in the cardiac action
      of carteolol. In peripheral arteries (femoral and tail) pre-contracted with
      phenylephrine, carteolol exerted ISA-related relaxing effects, independent of the
      presence of endothelium and sensitive to high concentrations (10 microM) of
      conventional beta-blockers. On the basis of these results, we propose to
      categorize carteolol as a non-conventional partial agonist of both cardiac and
      vascular beta-adrenoceptors.

PMID- 15153657
TI  - N-methyl-D-aspartate induces phosphorylation of cAMP response element (CRE)
      binding protein and increases DNA-binding activity of CRE in rat retina.
AB  - The aim of this study was to investigate whether an excitotoxic concentration of
      N-methyl-D-aspartate (NMDA) increases the expression of the phosphorylated cAMP
      response element-binding protein (p-CREB) and the DNA-binding activity of the
      cAMP response element (CRE) in rat retina. Intravitreal injection of NMDA was
      performed in adult male Wistar rats. p-CREB protein levels in the retina were
      examined by Western blot analysis. DNA-binding activity of CRE in the retina was
      evaluated by an electrophoretic mobility gel shift assay (EMSA). We confirmed
      that NMDA induced the reduction of ganglion cells and the inner plexiform layer
      of the retina. Western blot analysis showed increases in the expression of p-CREB
      in the retina 12 and 24 h after intravitreal NMDA injection and dimer formation
      of CREB in the nuclear fraction at 24 h. Increases of DNA-binding activity were
      observed in the retina 24 h after NMDA injection by EMSA. Our results suggest
      that phosphorylation of CREB may involved in NMDA-induced excitotoxicity in rat
      retina. Phosphorylated CREB seems to be the active form and the one that is
      transcribed.

PMID- 15153659
TI  - Calcineurin contributes to the enhancing effect of adenosine on nerve growth
      factor-induced neurite outgrowth via the decreased duration of p38 mitogen
      activated protein kinase phosphorylation.
AB  - Adenosine enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12
      cells. We found that adenosine increases NGF-induced phosphorylation of
      extracellular signal-regulated kinase (ERK), but decreases the duration of
      phosphorylation of p38 mitogen-activated protein (MAP) kinase. Therefore, we
      further examined the involvement of protein phosphatase in these effects of
      adenosine. FK506, a specific calcineurin inhibitor, inhibited the enhancing
      effect of adenosine on the NGF-induced neurite outgrowth and increased the
      duration of p38 MAP kinase phosphorylation without affecting ERK phosphorylation.
      These results suggest that adenosine decreases the duration of p38 MAP kinase via
      calcineurin activation, which contributes to the enhancement of NGF-induced
      neurite outgrowth.

PMID- 15153660
TI  - Changes in blood viscosity with mucopolysaccharide polysulfate.
AB  - We examined the dose-dependent effects of mucopolysaccharide polysulfate (MPS) on
      coagulation variables and whole-blood viscosity in human blood. Both 0.01% and
      0.1% MPS significantly reduced levels of both fibrin monomer and thrombin
      antithrombin III complex in a manner similar to that of 2.0 IU/ml heparin sodium.
      Furthermore, MPS dose-dependently decreased whole-blood viscosity, as measured
      with an oscillation viscometer. Because MPS can be applied in creams and gels,
      percutaneous application of MPS may effectively reduce whole-blood viscosity in
      local veins.

PMID- 15153661
TI  - T-588, a cognitive enhancer, protects against sodium nitroprusside-induced
      toxicity in cultured astrocytes.
AB  - The effects of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol
      hydrochloride (T-588), a cognitive enhancer, on sodium nitroprusside (SNP)
      induced cytotoxicity were examined in cultured rat astrocytes. Treatment with 100
      microM SNP for 72 h decreased cell viability and mitochondrial function assessed
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenil tetrazolium bromide (MTT) reduction
      activity, mitochondrial transmembrane potential, and intracellular ATP level. T
      588 at 100 microM prevented SNP-induced mitochondrial dysfunction and cell
      injury. Furthermore, T-588 increased MTT reduction activity without affecting
      cell proliferation in astrocytes. These results suggest that T-588 has a
      protective effect against SNP-mediated toxicity via improvement of mitochondrial
      dysfunction in astrocytes.

PMID- 15153662
TI  - Neuronal nitric oxide synthase as a novel anti-atherogenic factor.
AB  - Nitric oxide (NO) has multiple important actions that contribute to the
      maintenance of vascular homeostasis. NO is synthesized by three different
      isoforms of NO synthase (NOS), all of which have been reported to be expressed in
      human atherosclerotic vascular lesions. Although the regulatory roles of
      endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of
      atherosclerosis have been described, little is known about the role of neuronal
      NOS (nNOS). Recent studies have demonstrated that nNOS also exerts important
      vasculoprotective effects in vivo. In a carotid artery ligation model, nNOS
      knockout mice exhibited accelerated neointimal formation and constrictive
      vascular remodeling caused by blood flow disruption. In a rat balloon injury
      model, the selective inhibition of nNOS activity potently enhanced
      vasoconstrictor responses to a variety of calcium-mobilizing stimuli, and
      exacerbated neointimal formation. Moreover, in apolipoprotein E-knockout mice,
      deficiency of nNOS induced progression of aortic vascular lesion formation. In
      these models, nNOS was up-regulated in vascular lesions, and was predominantly
      expressed in the neointima and medial smooth muscle cells. These results provide
      the first direct evidence that nNOS plays important roles in suppressing
      arteriosclerotic vascular lesion formation. Thus, nNOS could be regarded as a
      novel anti-atherogenic factor.

PMID- 15153663
TI  - Plasma oxygen permeability may be a factor in atherosclerosis.
AB  - Plasma oxygen permeability measures how easily oxygen dissolves in and diffuses
      through blood plasma. There has long been evidence that artery wall hypoxia plays
      a role in atherogenesis. This paper reviews the influence that plasma oxygen
      permeability has on artery wall oxygenation and presents experimental evidence
      for a relationship between plasma oxygen permeability and clinically significant
      obstructive coronary artery disease. Thirty-eight inpatients referred for
      diagnostic cardiac catheterization were scored for active coronary artery
      disease, and their plasma oxygen permeabilities were measured. There was a
      statistically significant (p = 0.04) correlation between active coronary artery
      disease and plasma oxygen permeability. There were also statistically significant
      differences in mean plasma oxygen permeability both between patients who did and
      did not have actively progressing coronary artery disease (p = 0.01) and between
      patients who did and did not have clinically significant obstructive coronary
      artery disease, whether it was actively progressing or not (p = 0.02). These
      findings suggest that a decline in plasma oxygen permeability may be one of the
      many factors associated with progression of atherosclerosis and that substances
      which increase oxygen permeability might offer a useful adjunct to current
      therapeutic measures.

PMID- 15153664
TI  - Effects of fluvastatin in type 2 diabetic patients with hyperlipidemia: reduction
      in cholesterol oxidation products and VCAM-1.
AB  - The purpose of this study was to investigate the lipid-lowering and anti
      oxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase inhibitor, in type 2 diabetic patients. Six patients (3 men and 3
      women, mean age = 56.2) took 20 mg of fluvastatin once daily (at night) for 12
      weeks. Several markers of oxidative stress were then measured in these patients
      including plasma cholesterol oxidation products, i.e. oxysterols, and the levels
      of circulating adhesion molecules. Plasma total cholesterol levels were reduced
      by 12.3% in these individuals after 4 weeks of treatment, with levels remaining
      below 220 mg/dl for the entire treatment period. LDL levels were significantly
      reduced at 4 (18.1%) and 12 weeks (16.1%), and triglyceride levels were
      significantly reduced after 8 (22.5%) and 12 (37.7%) weeks of treatment. HDL-C
      levels increased from 50.7 +/- 15.4 prior to treatment to 63.8 +/- 24.3 mg/dl
      after 12 weeks of treatment, though this increase was not statistically
      significant. Lipid hydroperoxide, thiobarbituric acid-reactive substance (TBARS),
      and oxysterol levels were also reduced, suggesting that fluvastatin also had anti
      oxidative effects. Finally, VCAM-1 levels were similarly reduced by fluvastatin
      treatment. We conclude that fluvastatin safely improves the plasma lipid profile
      in type 2 diabetic patients with hyperlipidemia. We speculate that this drug
      might be doubly effective in reducing atherosclerosis and cardiac events in these
      patients as a result of its demonstrated anti-oxidative effects and its ability
      to reduce VCAM-1 levels.

PMID- 15153666
TI  - Effects of leptin receptor gene 3'-untranslated region polymorphism on metabolic
      profiles in young Japanese men.
AB  - We investigated the effects of leptin receptor gene 3'-untranslated region (3'
      UTR) polymorphism on clinical and metabolic parameters in 221 young Japanese men
      aged 21 to 28 years. The polymerase chain reaction-restriction fragment length
      polymorphism method was used to identify a pentanucleotide (CTTTA) insertion in
      3'-UTR of the leptin receptor gene. Body mass index, blood pressure, plasma
      glucose, insulin, leptin, total cholesterol, high-density lipoprotein (HDL)
      cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, free fatty
      acids, uric acid, apolipoprotein A-I (apoA-I), and cholesteryl-ester transfer
      protein levels were measured. There was only 1 homozygote and 38 heterozygotes
      for the 3'-UTR insertion allele among the 221 subjects. The insertion allele
      frequency was 0.090. Plasma HDL-cholesterol and apoA-I levels were significantly
      lower (p = 0.015 and p = 0.032 by Mann-Whitney U test, respectively) in
      homozygous or heterozygous carriers of the insertion allele than in subjects
      homozygous for the normal allele. There were no differences in other parameters
      measured. Furthermore, when the subjects were divided into three groups according
      to HDL-cholesterol level, the percentage of insertion allele-positive subjects
      was significantly lower in the highest HDL-cholesterol group (chi(2) = 8.42, p =
      0.015). These findings suggest that serum HDL-cholesterol and apoA-I levels are
      influenced by the leptin receptor gene 3'-UTR polymorphism in young Japanese men.

PMID- 15153665
TI  - Global analysis of RNA expression profile in human vascular cells treated with
      statins.
AB  - In addition to a lipid-lowering effect, 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) have an effect on the expression levels of many
      genes. In order to elucidate the range of this effect as comprehensively as
      possible, we investigated the changes in gene expression profiles brought about
      by atorvastatin or pitavastatin in cultured human umbilical vein endothelial
      cells (HUVEC), cultured human coronary artery smooth muscle cells (HCASMC) and
      cultured human hepatocarcinoma Hep G2 cells by means of DNA microarrays. Among
      the 6146 genes in the array, statins affected the expression levels of genes
      involved in coagulation, vascular constriction and cell growth in a cell-type
      specific manner. In HUVEC, they induced integrin beta4 and thrombomodulin
      profoundly, and profoundly suppressed pentraxin 3 both at 8 and 24 hours. In
      HCASMC, the statins induced thrombomodulin and urokinase inhibitor, and potently
      suppressed the cysteine-rich angiogenic inducer 61 and cyclin B. Many genes
      related to the cell cycle and/or growth were also regulated in HUVEC and HCASMC
      by the statins. These results indicate that many aspects of the pleiotropic
      effect can be mediated by transcriptional control by statins. Genes newly
      identified by this study may be useful in statin therapy.

PMID- 15153667
TI  - Interferon-gamma produced by bone marrow-derived cells attenuates atherosclerotic
      lesion formation in LDLR-deficient mice.
AB  - BACKGROUND: We evaluated the role of IFN-gamma produced by bone marrow-derived
      cells in atherogenesis in LDLR(-/-) mice using bone marrow transplantation (BMT).
      METHODS AND RESULTS: We generated IFN-gamma-deficient bone marrow transplanted
      LDLR(-/- )mice (IFN-gamma(-/-) BMT mice), and compared them with controls (IFN
      gamma(+/+) BMT mice). These mice were fed a high-fat diet (HFD). Plasma total
      cholesterol and triglyceride levels did not differ between these two groups.
      After 6 weeks of HFD feeding, the atherosclerotic lesions of IFN-gamma(-/-) BMT
      mice were larger than those of IFN-gamma(+/+) BMT mice at the aortic sinus,
      aortic arch and abdominal aorta. After 12 weeks of HFD feeding, the significant
      differences between the two groups disappeared except for the atherosclerotic
      lesion in the aortic sinus. MOMA2, CD4, CD8 or alpha-smooth muscle actin-positive
      cells were detected in the atherosclerotic lesions. The cellular composition of
      the lesions was identical between the two groups, but the cellular density showed
      decreased concomitant with the increased extracellular matrix deposition in IFN
      gamma(-/- )BMT mice. CONCLUSIONS: These findings demonstrate that IFN-gamma
      produced by bone marrow-derived cells delays the progression of atherosclerosis
      without any effect on plasma lipids, and this suppression may be due to decreased
      extracellular matrix deposition.

PMID- 15153668
TI  - A comparison of differences in the gene expression profiles of phorbol 12
      myristate 13-acetate differentiated THP-1 cells and human monocyte-derived
      macrophage.
AB  - In order to characterize the monocytic cell line THP-1 and its mature, macrophage
      like form treated with phorbol 12-myristate 13-acetate (PMA), we have conducted
      an oligonucleotide microarray assay and compared the results with those from an
      assay of human monocytes and macrophages. We found that early THP-1 cells have a
      pattern of gene expression distinct from monocytes, and when treated with PMA,
      certain genes which are induced in macrophages, such as apolipoprotein-E, matrix
      metalloproteinase 9 and alpha2 macroglobulin are also induced in the PMA-treated
      THP-1 cells (THP1PMA cells). However, these were some genes which are conversely
      regulated among macrophages and THP1PMA cells such as interleukin-1-beta and the
      overall correlation coefficient was not very high. It is shown that, although
      certain morphological and other characteristics of PMA-differentiated THP-1 cells
      are similar to macrophages, from a transcriptomic view, the two are different.
      This suggests a need for careful recognition of and allowance for this difference
      when interpreting the results of experiments done with THP-1 cells in which it is
      otherwise assumed they are representative of the macrophage.

PMID- 15153669
TI  - Histological and ultrastructural features in the early stage of Purkinje cell
      degeneration in the cerebellar calcification (CC) rat.
AB  - The cerebellar calcification (CC) rat is a new neurodegenerative mutant with
      severe Purkinje cell loss and symmetrical calcifications in the cerebellar cortex
      manifesting ataxia: lack of coordination in body movements. In the present study,
      histopathological features were examined in the Purkinje cell degeneration in
      postnatal homozygous suckling rats without clinical signs, which were genotyped
      by microsatellite markers. In addition, the calcified Purkinje cells were
      investigated ultrastructurally and elemental analysis was performed on the
      deposits. Body weight of the homozygous (cc/cc) rats was already slightly lower
      compared with the heterozygotes (cc/+) in the neonatal stage. The degeneration of
      the Purkinje cells in the cc/cc rats was recognized obviously in lobules VI, VII,
      VIII and IX from 14 days after birth, a few days before the appearance of the
      ataxic behavior. The Purkinje cells in the region along the fissure between the
      VIII and IX lobule areas were intensely positive for periodic acid-Schiff
      reaction specific to glycoconjugates, and in this region, calcium depositions
      were weakly positive for von Kossa's stain. Electron microscopy also revealed
      that the calcified Purkinje cells possessed numerous electron-dense bodies
      containing inclusions with cystic structures such as vesicles, mitochondria and
      lysosomes, and these bodies were mainly composed of calcium and phosphorous.
      These findings suggest abnormal storage of glycoconjugates might be a trigger of
      Purkinje cell degeneration and serves as a matrix for accumulation of calcium
      phosphate in the cerebellum of CC rats.

PMID- 15153670
TI  - Comparative study on picryl chloride (PCL)-induced contact dermatitis in female
      IQI/Jic and BALB/c mice.
AB  - Ear skin responses to picryl chloride (PCL)-induced contact dermatitis were
      compared in detail between IQI/Jic mice developed in Japan and BALB/c mice often
      used for the investigation of contact dermatitis. PCL was applied to the left ear
      of each mouse 4 (1st), 11 (2nd), 18 (3rd) and 25 days (4th) after sensitization
      of the abdominal skin with PCL. Time course examinations were carried out on the
      ear swelling responses, total IgE levels, skin histology and immunohistochemistry
      for infiltrated cells after the 1st and 4th application. In IQI mice, the peak
      time of the ear swelling responses tended to shift from 24 h to 9 h with marked
      elevation of total IgE levels and marked increase of mast cells showing
      degranulation after the 4th application when CD8(+) cells as well as CD4(+) cells
      also prominently increased. In BALB/c mice, except for the total IgE levels and
      the number of mast cells, the degrees of ear swelling responses, histological
      changes and increase of CD4(+) and CD8(+) cells were much less severe. Female IQI
      mice are considered to be a useful mouse strain for further investigations on the
      role of CD4(+) and CD8(+) T cells in the pathogenesis of contact dermatitis.

PMID- 15153672
TI  - Chromosomal mapping and zygosity check of transgenes based on flanking genome
      sequences determined by genomic walking.
AB  - Transgenes can affect transgenic mice via transgene expression or via the so
      called positional effect. DNA sequences can be localized in chromosomes using
      recently established mouse genomic databases. In this study, we describe a
      chromosomal mapping method that uses the genomic walking technique to analyze
      genomic sequences that flank transgenes, in combination with mouse genome
      database searches. Genomic DNA was collected from two transgenic mouse lines
      harboring pCAGGS-based transgenes, and adaptor-ligated, enzyme restricted genomic
      libraries for each mouse line were constructed. Flanking sequences were
      determined by sequencing amplicons obtained by PCR amplification of genomic
      libraries with transgene-specific and adaptor primers. The insertion positions of
      the transgenes were located by BLAST searches of the Ensembl genome database
      using the flanking sequences of the transgenes, and the transgenes of the two
      transgenic mouse lines were mapped onto chromosomes 11 and 3. In addition,
      flanking sequence information was used to construct flanking primers for a
      zygosity check. The zygosity (homozygous transgenic, hemizygous transgenic and
      non-transgenic) of animals could be identified by differential band formation in
      PCR analyses with the flanking primers. These methods should prove useful for
      genetic quality control of transgenic animals, even though the mode of transgene
      integration and the specificity of flanking sequences needs to be taken into
      account.

PMID- 15153671
TI  - Changes of renal lesion-related parameters in FGS/Nga and the parental mouse
      strains, CBA/N and RFM/Nga.
AB  - The FGS/Nga mouse strain, established from an outcross between CBA/N and RFM/Nga
      mice strains, has previously been reported as a spontaneous mouse model for focal
      glomerular sclerosis (FGS) and is considered to have two pairs of autosomal
      recessive genes associated with FGS. In this study, we examined the changes of
      seven renal lesion-related parameters, blood urea nitrogen (BUN), creatinine,
      albumin and total protein in plasma, urinary protein, systolic blood pressure,
      and a glomerulosclerosis index on histological observation, in 20-week-old
      FGS/Nga mice and their age-matched two parental strains, CBA/N and RFM/Nga. The
      levels of plasma BUN and creatinine, urinary protein and systolic blood pressure
      were significantly increased in FGS/Nga, compared with those of the parental
      strains. RFM/Nga mice showed slightly elevated levels of all biochemical makers.
      In histological analysis, a higher glomerulosclerosis index was observed in
      FGS/Nga than the two parental strains. RFM/Nga mice appeared to have slight
      sclerotic lesions of glomeruli, but no renal failure was observed in CBA/N mice.
      These results suggest that at least one mutant gene that causes the progression
      of renal lesion in FGS/Nga mice is derived from RFM/Nga.

PMID- 15153673
TI  - Intratracheal administration of bleomycin via a catheter in unanesthetized rats.
AB  - In order to ensure a widespread distribution in the lung and to avoid the effect
      of anesthesia, bleomycin at a total dose of 4.5 or 6.0 mg/kg was administered in
      four divided doses (0.5 ml/kg/time) at intervals of 2 h to male rats via a
      catheter (tracheotomy tube) without anesthesia. In comparison to vehicle (saline)
      controls, bleomycin-treated rats showed a significant suppression of body weight
      gain that was observed transiently at 4.5 mg/kg and continuously (throughout the
      3-week observation period) at 6.0 mg/kg. Histopathologically, interstitial
      pneumonitis, thickening of alveolar walls, thickening of pulmonary arterial
      walls, foamy cells in alveoli, and hemorrhage were observed in both 4.5 and 6
      mg/kg groups, and also emphysema in the 6 mg/kg group. Both groups exhibited a
      significant decrease in the partial pressure of arterial oxygen (PaO(2)) and a
      significant increase in alveolar-arterial oxygen tension difference (AaDO(2)),
      and a significant increase in erythrocyte count was observed in the 6 mg/kg
      group. Furthermore, both treated groups showed a significant increase in the
      ratio of the right ventricular weight versus left ventricle plus septum weights.
      The significant increase in erythrocyte count might have been caused by diffusion
      disturbance and ventilation-perfusion imbalance due to the pulmonary damage.
      These findings suggest that the present experimental method will be useful for
      clarification of the pulmonary damage induced by bleomycin in rats.

PMID- 15153674
TI  - The daily pattern of heart rate, body temperature, locomotor activity, and
      autonomic nervous activity in congenitally bronchial-hypersensitive (BHS) and
      bronchial-hyposensitive (BHR) guinea pigs.
AB  - We studied the characteristics of the rhythmicity of heart rate (HR), body
      temperature (BT), locomotor activity (LA) and autonomic nervous activity in
      bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. For
      this purpose, HR, BT, LA, and electrocardiogram (ECG) were recorded from
      conscious and unrestrained guinea pigs using a telemetry system. Autonomic
      nervous activity was analyzed by power spectral analysis of heart rate
      variability. Nocturnal patterns, in which the values in the dark phase (20:00
      06:00) were higher than those in the light phase (06:00-20:00), were observed in
      HR, BT and LA in both strains of guinea pigs. The autonomic nervous activity in
      BHS guinea pigs showed a daily pattern, although BHR guinea pigs did not show
      such a rhythmicity. The high frequency (HF) power in BHS guinea pigs was higher
      than that in BHR guinea pigs throughout the day. Moreover, the low frequency/high
      frequency (LF/HF) ratio in BHS guinea pigs was lower than that in BHR guinea pigs
      throughout the day. These results suggest that parasympathetic nervous activity
      may be predominant in BHS guinea pigs.

PMID- 15153675
TI  - New mutant mouse with skeletal deformities caused by mutation in delta like 3
      (Dll3) gene.
AB  - We have established a new mouse strain with vertebral deformities caused by an
      autosomal single recessive mutation (oma). The mutant mice showed short trunk and
      short and kinky tail. The skeletal preparations of newborn and prenatal mice
      showed disorganized vertebrae and numerous vertebral and rib fusions which are
      thought to be caused by patterning defects at the stage of somitegenesis. Linkage
      analysis localized the oma locus on the proximal region of mouse chromosome 7
      close to Dll3 gene. Dll3 is the gene involved in the Notch signaling pathway and
      null-mutation of the gene has been reported to cause vertebral deformities. The
      phenotypic similarity between oma and Dll3 null-mutant mice suggests that the
      causative gene for the oma mutant is the Dll3 gene. We, therefore, investigated
      the nucleotide sequence of the Dll3 gene of the oma mouse and found a single
      nucleotide substitution of G to T which causes missense mutation of glycine to
      cysteine at codon 409. Since the amino acid substitution is a nonconservative
      amino acid substitution at the conserved portion of the Dll3 protein, and the
      substitution is specific to the mutant mice, we concluded that the nucleotide
      substitution of the Dll3 gene is responsible for the skeletal deformities of the
      oma mouse.

PMID- 15153676
TI  - Characteristics of autonomic nervous function in Zucker-fatty rats: investigation
      by power spectral analysis of heart rate variability.
AB  - We investigated the characteristics of autonomic nervous function in Zucker-fatty
      and Zucker-lean rats. For this purpose, a long-term electrocardiogram (ECG) was
      recorded from conscious and unrestrained rats using a telemetry system, and the
      autonomic nervous function was investigated by power spectral analysis of heart
      rate variability (HRV). Although heart rate (HR) in Zucker-fatty rats was lower
      than that in Zucker-lean rats throughout 24 h, apparent diurnal variation in HR
      was observed in both strains and HR during the dark period was significantly
      higher than that in light period. Diurnal variation in locomotor activity (LA) in
      Zucker-fatty rats was also observed, but LA was lower than that in Zucker lean
      rats, especially during the dark period. There were no significant differences,
      however, in high-frequency (HF) power, low-frequency (LF) power, and the LF/HF
      ratio between Zucker-fatty and Zucker-lean rats. The circadian rhythm of these
      parameters was mostly preserved in both strains of rats. Moreover, the effect of
      autonomic blockades on HRV was nearly the same in Zucker-fatty and Zucker-lean
      rats. These results suggest that the autonomic nervous function of insulin
      resistant Zucker-fatty rats remain normal, from the aspect of power spectral
      analysis of HRV.

PMID- 15153677
TI  - Functional development of oligodendrocytes and open-field behavior in developing
      rats: an approach using monoclonal antibody to immature oligodendrocytes.
AB  - To examine the relation between functional development of oligodendrocytes and
      open-field behavior during the postnatal period, a mouse monoclonal antibody
      termed 14F7, which predominantly labels stage-specific immature oligodendrocytes,
      was employed. Antibody 14F7 was administered intraperitoneally into male pups on
      day 3 and 4 after birth. The open-field test was performed on days 12 and 18 of
      the postnatal period. Horizontal activity increased remarkably with the growth of
      pups. On day 18, horizontal activity in the group with 14F7 was significantly
      higher than the control, while there was no significant difference between
      treatments on day 12. In contrast to the horizontal activity, the frequency of
      hind leg rearing, vertical activity, in the group with 14F7 was significantly
      lower than that in the control. On day 12, choline acetyltransferase (ChAT) and
      acetylcholinesterase (AChE) activities in the cerebral cortex were similar
      between the groups. These activities increased with the growth of pups in both
      groups. In the 14F7 group on day 18, ChAT activity was the same as the control,
      whereas AChE activity was significantly lower compared with the control. These
      results suggest that neonatal exposure to 14F7 induces abnormal neurotransmission
      by reducing the degradation of acetylcholine and alters the spontaneous
      activities in developing rats.

PMID- 15153678
TI  - Update of mouse microsatellite database of Japan (MMDBJ).
AB  - We updated a database of microsatellite marker polymorphisms found in inbred
      strains of the mouse, most of which were derived from the wild stocks of four Mus
      musculus subspecies, M. m. domesticus, M. m. musculus, M. m.castaneus and M. m.
      molossinus. The major aim of constructing this database was to establish the
      genetic status of these inbred strains as resources for linkage analysis and
      positional cloning. The inbred strains incorporated in our database are A/J,
      C57BL/6J, CBA/J, DBA/2J, SM/J, SWR/J, 129Sv/J, MSM/Ms, JF1/Ms, CAST/Ei, NC/Nga,
      BLG2/Ms, NJL/Ms, PGN2/Ms, SK/CamEi and SWN/Ms, which have not or have only been
      poorly incorporated in the Whitehead Institute/MIT (WI/MIT) microsatellite
      database. The number of polymorphic microsatellite loci incorporated in our
      database is over 1,000 in all strains, and the URL site for our database is
      located at http:// www.shigen.nig.ac.jp /mouse/mmdbj/mouse.html.

PMID- 15153679
TI  - Determination of the rdw rat genotype by polymerase chain reaction with allele
      specific primer (PCR-ASP).
AB  - The rat carrying the rdw mutation (rdw rat) is a dwarf mutant with hypothyroidism
      that is caused by a single G to C transversion in the thyroglobulin gene.
      Therefore, the development of a simple method for molecular-based genotyping of
      this mutation has been problematic. We have developed a rapid and simple
      genotyping method that provides identification of both the rdw and wild-type
      allele. This polymerase chain reaction with an allele-specific primer (PCR-ASP)
      method amplifies only the specific allele, wild or mutant type, by using 3'
      terminal mismatched primers that pair only with the respective alleles. This
      assay should be of value for rdw colony control and rapid discrimination of
      rdw/rdw, rdw/+ and +/+ rats.

PMID- 15153680
TI  - Age-related changes in serum/plasma biochemical parameters of WHHLMI rabbits.
AB  - We developed myocardial infarction-prone rabbits (WHHLMI rabbits) by selectively
      breeding coronary atherosclerosis-prone WHHL rabbits. To examine the serum/plasma
      biochemical parameters of this animal model, we assayed the lipid and glucose
      levels, and enzyme activities of WHHLMI rabbits from 2 to 26 months of age using
      solid phase analysis. The results showed a good correlation with those measured
      with a conventional method. The serum enzyme activities and lipid levels varied
      with aging despite almost no change in the plasma glucose levels. Gender
      differences were observed in the total cholesterol, triglyceride, and lactate
      dehydrogenase activity levels. The data on these serum/plasma biochemical
      parameters will be useful in studies of myocardial infarction or pharmacological
      studies using this model.

PMID- 15153682
TI  - Differences in responsiveness of mouse strain against p-benzoquinone as assessed
      by non-radioisotopic murine local lymph node assay.
AB  - The non-radioisotopic modification of murine local lymph node assay (LLNA) by
      using 5-bromo-2'-deoxyuridine (BrdU) was conducted to investigate the strain
      related difference of the responsiveness of mice to p-benzoquinone (PBQ) with
      BALB/cAnN, CBA/JN and CD-1 mouse strains. Strain and dose related differences
      were analyzed by two-way analysis of variance (two-way ANOVA). CBA/JN was
      considered to be the highest responsive strain to PBQ, and interaction was
      detected between CD-1 and each of the other inbred strains. These results support
      the recommendation in the OECD test guideline 429 and the skin sensitization test
      guideline of US-EPA with regard to the selection of mouse strain for LLNA.

PMID- 15153681
TI  - The susceptibility of pregnant mice to encephalomyocarditis (EMC) virus infection
      on different days of gestation.
AB  - Pregnant mice of the BALB/c CrSlc strain were experimentally infected with the D
      variant of encephalomyocarditis virus (EMC-D, 5 x 10(2) PFU/head) on three
      different gestational days (GD). Mice were intraperitoneally inoculated with EMC
      D on 11, 13 and 15 GD and sacrificed 3 days post inoculation. There was no
      significant difference in the fetal mortality among all inoculation groups.
      Placenta showed higher virus titer than fetus and dam's serum in all inoculation
      groups, and the virus titer of the fetus was lowest in the 15GD group.
      Histopathological changes and signals of viral RNAs detected by in situ
      hybridization were observed almost restricted to the spongiotrophoblast layer of
      the placenta in all inoculation groups, and the signals were strongest in the
      11GD group. In the fetus of the11GD group, signals of viral RNAs were also seen
      in myocardium and hepatocytes. Ultrastructurally, intracytoplasmic aggregations
      of virus-like particles in crystalline array were observed in trophoblast cells
      and giant cells in the spongiotrophoblast layer in all inoculation groups.

PMID- 15153683
TI  - Repeated streptozotocin injections cause early onset of glomerulosclerosis in
      mice.
AB  - Diabetic nephropathy (DN), a major cause of end-stage chronic renal failure, is
      histologically characterized by glomerulosclerosis. To investigate the molecular
      mechanisms of DN, it is important to establish a stable model of
      glomerulosclerosis in mice, because genomic manipulation techniques (such as gene
      destruction or transgene insertion) are well established in rodent species. In
      this study, we found that repeated administrations of streptozotocin led to early
      onset of glomerular sclerotic lesions in C57BL/6 mice, accompanied with renal
      dysfunction. During the natural course of DN, glomerular endothelial cells
      decreased at 10 weeks after the start of streptozotocin-injections, whereas
      myofibroblastic mesangial cells became evident. Our results provide an animal
      tool to elucidate the molecular mechanisms of DN, for example to investigate
      vascular pathology in diabetic glomerular diseases.

PMID- 15153684
TI  - Examination of fetal cells and cell-free fetal DNA in maternal blood for fetal
      gender determination.
AB  - BACKGROUND: To assess applicability of noninvasive methods for prenatal sex
      determination, both intact fetal cells and cell-free DNA from maternal blood were
      studied. METHODS: Maternal peripheral blood samples were obtained from 41 women
      carrying chromosomally normal fetuses and from 3 women with aneuploid fetuses
      (47,XX,+18; 47,XY,+18 and 47,XY,+21) at 9-22 weeks of gestation. DNA was
      extracted from the plasma fraction and analyzed by the nested polymerase chain
      reaction (PCR) using Y chromosome specific primers. After fetal cells were
      enriched by MACS, fluorescence in situ hybridization (FISH) with chromosome X and
      Y specific probes was performed to detect XY cells. RESULTS: Although Y
      chromosome-specific DNA was detected by PCR analysis in all maternal plasma
      samples with male fetuses, 26% women bearing female fetuses also gave positive
      results. By FISH analysis, XY cells were detected in not only 58% of women
      bearing male fetuses, but also 13% of their counterpoints with female fetuses.
      CONCLUSIONS: Our findings suggested that consistent results for fetal gender
      using PCR or FISH cannot be obtained with intact fetal cells and cell-free DNA
      present in maternal blood and plasma at 9-22 weeks of gestation, despite their
      apparent abundant presence.

PMID- 15153685
TI  - Clinical manifestations and treatment of caries from 1953 to global changes in
      the 20th century.
AB  - Manifestations and treatment of caries are strongly dependent on caries risk and
      the severity of the attacking factors which determine the degree of caries
      activity. Caries activity in turn will be modified and can be minimized by
      effective preventive measures. Exemplary cases and events will be discussed to
      illustrate what has happened since the establishment of ORCA 50 years ago.

PMID- 15153686
TI  - Changes in dental caries 1953-2003.
AB  - In the first half of the 20th century, indices and methods of conducting surveys
      of the level of dental diseases were developed. Modern epidemiological studies
      began in the fifties and many reliable studies have been conducted after 1960. In
      the following decades, a substantial decline of caries prevalence was documented
      in the majority of the highly industrialized countries, with reductions of
      lifetime caries experience exceeding 75%. The decline comes to an end when low or
      very low levels of prevalence are reached. Children of low socioeconomic status
      and immigrants from outside Western Europe, however, generally have higher
      disease levels and may cause increases in caries prevalence. For this and other
      reasons, caries epidemiology will remain an indispensable part of dental public
      health.

PMID- 15153688
TI  - Diagnosis versus detection of caries.
AB  - Caries diagnosis is the art or act of identifying a disease from its signs and
      symptoms. This is distinct from the detection of the signs and symptoms
      themselves. The diagnosis forms the basis for making informed treatment
      decisions. Hence, if there is no diagnostic step expressed in terms of the
      probability of present and future occurrence of disease, practitioners may resort
      to treatments guided by previous experiences with similar clinical
      manifestations. This paper reviews various methodological aspects of caries
      diagnostic testing. It is concluded that rather than continuing to search for the
      truth of the diagnosis, it may be more informative to consider the consequences
      of the diagnosis. This view is supported by results from caries-preventive trials
      in which the activity of carious lesions has been monitored longitudinally over
      years.

PMID- 15153687
TI  - Changing paradigms in concepts on dental caries: consequences for oral health
      care.
AB  - Kuhn proposed in his Structure of Scientific Revolutions (1962) that the
      theoretical framework of a science (paradigm) determines how each generation of
      researchers construes a causal sequence. Paradigm change is infrequent and
      revolutionary; thereafter previous knowledge and ideas become partially
      redundant. This paper discusses two paradigms central to cariology. The first
      concerns the most successful caries-preventive agent: fluoride. When it was
      thought that fluoride had to be present during tooth mineralisation to 'improve'
      the biological apatite and the 'caries resistance' of the teeth, systemic
      fluoride administration was necessary for maximum benefit. Caries reduction
      therefore had to be balanced against increasing dental fluorosis. The 'caries
      resistance' concept was shown to be erroneous 25 years ago, but the new paradigm
      is not yet fully adopted in public health dentistry, so we still await real
      breakthroughs in more effective use of fluorides for caries prevention. The
      second paradigm is that caries is a transmittable, infectious disease: even one
      caused by specific microorganisms. This paradigm would require caries prevention
      by vaccination, but there is evidence that caries is not a classical infectious
      disease. Rather it results from an ecological shift in the tooth-surface biofilm,
      leading to a mineral imbalance between plaque fluid and tooth and hence net loss
      of tooth mineral. Therefore, caries belongs to common 'complex' or
      'multifactorial' diseases, such as cancer, cardiovascular diseases, diabetes, in
      which many genetic, environmental and behavioural risk factors interact. The
      paper emphasises how these paradigm changes raise new research questions which
      need to be addressed to make caries prevention and treatment more cost-effective.

PMID- 15153689
TI  - Diagnostic levels in dental public health planning.
AB  - This concept paper discusses the rationale for using different diagnostic
      criteria for dental caries in public health programs. The author contends that
      epidemiological data or needs assessment surveys should collect data to provide
      information on the epidemiology of different stages of the caries process in
      order to enable planners to design tailored programs to prevent dental caries. In
      a rapidly progressing caries environment, conventional approaches to delivering
      preventive measures may not work. The author also contends that dental public
      health programs should expand their vision to influence how dentists are
      detecting, diagnosing and managing dental caries. Dentists' restorative decisions
      have significant impact on the oral health status of a nation. Henceforth,
      detecting the early or noncavitated caries level and preventing these lesions
      from progressing to the cavitated stage (or being restored) could have a
      significant impact on the oral health status around the world. There is a need
      for more research on the best methods to detect, prevent and treat early carious
      lesions.

PMID- 15153690
TI  - Dental plaque as a microbial biofilm.
AB  - New technologies have provided novel insights into how dental plaque functions as
      a biofilm. Confocal microscopy has confirmed that plaque has an open architecture
      similar to other biofilms, with channels and voids. Gradients develop in areas of
      dense biomass over short distances in key parameters that influence microbial
      growth and distribution. Bacteria exhibit an altered pattern of gene expression
      either as a direct result of being on a surface or indirectly as a response to
      the local environmental heterogeneity within the biofilm. Bacteria communicate
      via small diffusible signalling molecules (e.g. competence-stimulating peptide,
      CSP; autoinducer 2); CSP induces both genetic competence and acid tolerance in
      recipient sessile cells. Thus, rates of gene transfer increase in biofilm
      communities, and this is one of several mechanisms (others include: diffusion
      reaction, neutralization/inactivation, slow growth rates, novel phenotype) that
      contribute to the increased antimicrobial resistance exhibited by bacteria in
      biofilms. Oral bacteria in plaque do not exist as independent entities but
      function as a co-ordinated, spatially organized and fully metabolically
      integrated microbial community, the properties of which are greater than the sum
      of the component species. A greater understanding of the significance of dental
      plaque as a mixed culture biofilm will lead to novel control strategies.

PMID- 15153691
TI  - Application of the Zurich biofilm model to problems of cariology.
AB  - The term biofilm is increasingly replacing 'plaque' in the literature, but
      concepts and existing paradigms are changing much more slowly. There is little
      doubt that biofilm research will lead to more realistic perception and
      interpretation of the physiology and pathogenicity of microorganisms colonizing
      plaques in the oral cavity. There is clear evidence that the genotypic and
      phenotypic expression profiles of biofilm and planktonic bacteria are different.
      Several techniques are available today to study multispecies biofilms of oral
      bacteria, each having its particular advantages and weaknesses. We describe a
      biofilm model developed in Zurich and demonstrate a number of applications with
      direct or indirect impact on prophylactic dentistry: spatial arrangement and
      associative behavior of various species in biofilms; multiplex fluorescent in
      situ hybridization analysis of oral bacteria in biofilms; use of the biofilm
      model to predict in vivo efficacy of antimicrobials reliably; mass transport in
      biofilms; de- and remineralization of enamel exposed to biofilms in vitro. The
      potential of biofilm experimentation in oral biology has certainly not yet been
      fully exploited and dozens of possible interesting applications could be
      investigated. The overall physiological parameters of multispecies biofilms can
      be measured quite accurately, but it is still impossible to assess in toto the
      multitude of interactions taking place in such complex systems. What can and
      should be done is to test hypotheses stemming from experiments with planktonic
      cells in monospecies cultures. In particular, it will be interesting to
      investigate the relevance to biofilm composition and metabolism of specific gene
      products by using appropriate bacterial mutants.

PMID- 15153692
TI  - Antimicrobials in future caries control? A review with special reference to
      chlorhexidine treatment.
AB  - The aim of this paper was to examine recent evidence for the effect of the
      antibacterial approach to prevent and control caries with special reference to
      the use of chlorhexidine (CHX). Existing information from the mid 1990s provided
      limited evidence for the effectiveness of CHX gels, rinses and toothpaste in
      preventing caries in permanent teeth of children and adolescents. An updated
      literature search on CHX intervention in controlled clinical trials from 1995 to
      May 2003 unveiled 22 studies covering over 4,500 patients with clinical caries as
      end point. The vast majority (n = 21) were dealing with CHX-containing varnishes.
      Since the studies exhibited disparities in design, diagnosis and intervention,
      the findings were subgrouped with respect to caries type and localization.
      According to the ranking system of the Swedish Council on Technology Assessment
      in Health Care, the evidence for an anticaries effect of CHX varnishes was rated
      as inconclusive for caries-active schoolchildren and adolescents with regular
      fluoride exposure. Regarding fissure caries, a preventive effect of CHX varnishes
      was demonstrated in 4 studies out of 5 when compared to no treatment in children
      with low fluoride exposure. The evidence for arresting root caries in dry-mouth
      patients and frail elderly subjects was inconclusive. In conclusion, the evidence
      from the recent literature was inconclusive for the use of CHX varnishes for
      caries prevention in risk groups.

PMID- 15153693
TI  - A Caries Vaccine? The state of the science of immunization against dental caries.
AB  - Studies performed in numerous laboratories over several decades have demonstrated
      the feasibility of immunizing experimental rodents or primates with protein
      antigens derived from Streptococcus mutans or Streptococcus sobrinus against oral
      colonization by mutans streptococci and the development of dental caries.
      Protection has been attributed to salivary IgA antibodies which can inhibit
      sucrose-independent or sucrose-dependent mechanisms of streptococcal accumulation
      on tooth surfaces according to the choice of vaccine antigen. Strategies of
      mucosal immunization have been developed to induce high levels of salivary
      antibodies that can persist for prolonged periods and to establish immune memory.
      Studies in humans show that salivary antibodies to mutans streptococci can be
      induced by similar approaches, and that passively applied antibodies can also
      suppress oral re-colonization by mutans streptococci. Progress towards practical
      vaccine development requires evaluation of candidate vaccines in clinical trials.
      Promising strategies of passive immunization also require further clinical
      evaluation.

PMID- 15153694
TI  - How much saliva is enough for avoidance of xerostomia?
AB  - Xerostomia, the subjective sensation of dry mouth, occurs when the salivary flow
      rate is less than the rate of fluid loss from the mouth by evaporation and by
      absorption of water through the oral mucosa. Evaporation can only occur during
      mouth-breathing but could reach a maximum rate of about 0.21 ml/min at rest,
      although normally it would be much less. Water absorption through the mucosa can
      occur because saliva has one sixth the osmotic pressure of extracellular fluid,
      thus creating a water gradient across the mucosa. The maximum absorption rate is
      calculated to be about 0.19 ml/min, declining to zero as the saliva reaches
      isotonicity. A recent study found the residual saliva volume, the volume of
      saliva left in the mouth after swallowing, to be 71% of normal in patients with
      severe hyposalivation and whose mouths felt very dry. Saliva in the residual
      volume is present as a thin film which varies in thickness with site. The hard
      palate has the thinnest film and when this is <10 microm thick, evaporation
      during mouth-breathing and/or fluid absorption may rapidly decrease it to zero,
      resulting in xerostomia. This is also generally associated with reduced secretion
      from the soft palate minor glands, which may contribute to the film on the hard
      palate. Thus, xerostomia appears to be due, not to a complete absence of oral
      fluid, but to localized areas of mucosal dryness, notably in the palate.
      Unstimulated salivary flow rates >0.1-0.3 ml/min may be necessary for this
      condition to be avoided.

PMID- 15153695
TI  - Salivary enhancement therapies.
AB  - When salivary output is reduced chronically to a significant extent, there is a
      marked increase in dental caries. As the role of saliva in protection of the oral
      hard tissue is well recognized, there have long been efforts to enhance salivary
      function in conditions with associated secretory hypofunction. The rationale is
      that by stimulating salivary output, caries and other oral complications will be
      reduced or eliminated. The most widely used method for increasing salivary
      function is a combination of masticatory and gustatory stimulation. A large
      number of systemic agents have also been proposed as secretagogues, but only a
      few have shown consistent salivary enhancing properties in well-designed,
      controlled trials. Pilocarpine has been shown to improve symptoms of oral dryness
      and to increase salivary output in patients with Sjogren's syndrome and
      postradiation xerostomia. Recently, cevimeline has shown significant salivary
      enhancement in Sjogren's syndrome. Pilocarpine and cevimeline have a similar
      mechanism of action, side effect profile and duration of activity. No
      secretagogues have been linked directly in clinical trials to either caries
      prevention or a reduction in the existing caries rate of salivary dysfunction
      patients. Improved secretagogues are needed, with fewer side effects, increased
      duration of activity and greater potency. Future research directions include gene
      therapeutic approaches to direct salivary growth and differentiation or modify
      remaining tissues to promote secretion, creation of a biocompatible artificial
      salivary gland and salivary transplantation. With improved secretagogues, the
      effects of conditions that result in reduced salivary function and increased
      caries will be ameliorated.

PMID- 15153697
TI  - Fluorides in caries prevention and control: empiricism or science.
AB  - The caries-preventive effects of fluoride are beyond any reasonable doubt!
      Inclusion of fluoride use in caries prevention protocols has resulted in
      significant reduction in caries prevalence in the majority of the population.
      Nevertheless, even in low-caries prevalence populations up to 20% of individuals
      may suffer to an unacceptable degree from caries. In the history of caries
      research various phases can be discerned. Starting with the initial - laboratory 
      studies to reveal the mode of action of fluoride, attention later shifted to
      intra-oral studies and in situ product testing. Currently much emphasis is given
      to evidence-based dentistry and guidelines for clinical practice, which trend has
      also focussed the research on fluoride and caries. While on some topics, such as
      the efficacy of fluoride toothpastes, evidence is convincing, additional research
      is indicated to resolve remaining questions. One such question is that of high
      prevalence individuals for which a comprehensive research programme focussing
      both on caries aetiological and behavioural aspects should be further developed.
      Efforts should continue to be directed at improving our understanding of
      fluoride, in particular on topics where success so far has failed.

PMID- 15153696
TI  - Salivary proteins: protective and diagnostic value in cariology?
AB  - Saliva is essential for a lifelong conservation of the dentition. Various
      functions of saliva are implicated in the maintenance of oral health and the
      protection of our teeth: (i) The tooth surface is continuously protected against
      wear by a film of salivary mucins and proline-rich glycoprotein. (ii) The early
      pellicle proteins, proline-rich proteins and statherin, promote remineralization
      of the enamel by attracting calcium ions. (iii) Demineralization is retarded by
      the pellicle proteins, in concert with calcium and phosphate ions in saliva and
      in the plaque fluid. (iv) Several salivary (glyco)proteins prevent the adherence
      of oral microorganisms to the enamel pellicle and inhibit their growth. (v) The
      salivary bicarbonate/carbonate buffer system is responsible for rapid
      neutralization of acids. An overview is presented on the major antimicrobial
      systems in human saliva. Not only the well-known major salivary glycoproteins,
      including mucins, proline-rich glycoprotein and immunoglobulins, but also a
      number of minor salivary (glyco)proteins, including agglutinin, lactoferrin,
      cystatins and lysozyme, are involved in the first line of defense in the oral
      cavity. Besides, small cationic antimicrobial peptides, e.g. defensins,
      cathelicidin and the histatins, have come into focus. These are potentially
      suited as templates for the design of a new generation of antibiotics, since they
      kill a broad spectrum of microorganisms, while hardly evoking resistance, in
      contrast to the classical antibiotics.

PMID- 15153698
TI  - Systemic versus topical fluoride.
AB  - The actual mechanism of fluoride action is still a subject of debate. A dogma has
      existed for many decades, that fluoride has to be ingested and acts mainly pre
      eruptively. However, recent studies concerning the systemic effect of fluoride
      supplementation concluded that the caries-preventive effect of fluoride is almost
      exclusively posteruptive. Moreover, epidemiologists have cast doubt on the
      validity of the 'old' studies dealing with fluoride use. The concept of the
      posteruptive fluoride effect is supported by in vitro and in situ investigations
      demonstrating that the mode of action of fluoride can be attributed mainly to its
      influence on de- and remineralization kinetics of dental hard tissues. Therefore,
      topical fluoride application (e.g. in the form of fluoridated dentifrices) should
      be encouraged. There are still important questions open that need to be answered
      despite existing knowledge about the caries-preventive effect of fluoride.

PMID- 15153699
TI  - How to improve the effectiveness of caries-preventive programs based on fluoride.
AB  - During recent years, an increasing number of reports have been published in which
      the observed caries-preventive effect of fluoride has been lower than could have
      been expected on the basis of the earlier literature. The current low levels of
      caries occurrence and the widespread use of fluoridated toothpastes as well as
      other fluoride products and methods have been suggested as reasons for the
      reduced relative effect of fluoride from any single source. Theoretically, one
      can improve the effectiveness of fluoride in caries-preventive programs by using
      measures that are more effective than the previous ones and still safe and
      feasible in everyday conditions. Another possibility is to direct fluoride-based
      prevention to high caries risk susceptible individuals who are most likely to
      benefit from it. Thirdly, one can enhance the intensity of existing fluoride
      prevention by increasing the frequency of applications, but this is of course
      worthwhile only if the recipients are lacking sufficient exposure to fluoride. In
      theory, people themselves could easily take care of their adequate fluoride
      supply by using fluoride toothpastes and/or other home use products frequently
      enough to maintain a sufficient salivary fluoride concentration at all times.
      Many people are unwilling to adopt healthy lifestyles, however, and therefore
      caries-preventive programs will remain necessary for the foreseeable future.
      Fluoride is the backbone of all such programs. Since conditions strongly
      determine the usefulness of caries prevention including different fluoride
      regimes, more research is still needed to monitor the effectiveness of caries
      preventive programs and their components in variable conditions of today and
      tomorrow.

PMID- 15153700
TI  - The effect of fluoride on the developing tooth.
AB  - This review aims to outline the effects of fluoride on the biological processes
      involved in the formation of tooth tissues, particularly dental enamel. Attention
      has been focused on mechanisms which, if compromised, could give rise to dental
      fluorosis. The literature is extensive and often confusing but a much clearer
      picture is emerging based on recent more detailed knowledge of odontogenesis.
      Opacity, characteristic of fluorotic enamel, results from incomplete apatite
      crystal growth. How this occurs is suggested by other changes brought about by
      fluoride. Matrix proteins, associated with the mineral phase, normally degraded
      and removed to permit final crystal growth, are to some extent retained in
      fluorotic tissue. Fluoride and magnesium concentrations increase while carbonate
      is reduced. Crystal surface morphology at the nano-scale is altered and
      functional ameloblast morphology at the maturation stage also changes. Fluoride
      incorporation into enamel apatite produces more stable crystals. Local
      supersaturation levels with regard to the fluoridated mineral will also be
      elevated facilitating crystal growth. Such changes in crystal chemistry and
      morphology, involving stronger ionic and hydrogen bonds, also lead to greater
      binding of modulating matrix proteins and proteolytic enzymes. This results in
      reduced degradation and enhanced retention of protein components in mature
      tissue. This is most likely responsible for porous fluorotic tissue, since matrix
      protein removal is necessary for unimpaired crystal growth. To resolve the
      outstanding problems of the role of cell changes and the precise reasons for
      protein retention more detailed studies will be required of alterations to cell
      function, effect on specific protein species and the nano-chemistry of the
      apatite crystal surfaces.

PMID- 15153701
TI  - Sugars - the arch criminal?
AB  - Numerous lines of evidence have conclusively established the role of sugars in
      caries etiology and the importance of sugars as the principal dietary substrate
      that drives the caries process has not been scientifically challenged. While
      sugars appear to differ little in acidogenic potential, sucrose has been given
      special importance, as the sole substrate for synthesis of extracellular glucans.
      Water-insoluble glucans might enhance accumulation of mutans streptococci on
      smooth tooth surfaces and appear to enhance virulence by increasing plaque
      porosity, resulting in greater acid production immediately adjacent to the tooth
      surface. Data indicating that the sugar consumption/caries relationship is now
      weaker have led to suggestions that recommendations to restrict sugar consumption
      are no longer necessary. Clearly, fluoride has raised the threshold of sugar
      intake at which caries will progress to cavitation, but fluoride has its limits,
      and caries remains a serious problem for disadvantaged individuals in many
      industrialized countries and is a rising problem in many developing countries. A
      weakening of the sugar/caries relationship may also be explained by many
      technical, biological, behavioral and genetic factors. Future research should aim
      to determine the biologic and behavioral factors that influence caries risk.
      Measures to educate the public on the dangers of frequent sugar consumption,
      combined with recommendations for proper oral hygiene and fluoride use, are still
      warranted. Individual dietary counseling is highly recommended for patients at
      high caries risk. As dental caries is a preventable disease, each country must
      decide: what level of disease is society willing and able to tolerate?

PMID- 15153702
TI  - Sugar alcohols: what is the evidence for caries-preventive and caries-therapeutic
      effects?
AB  - The most widely used sugar alcohols are: xylitol, sorbitol, mannitol, maltitol,
      lactitol and the products Lycasin and Palatinit. It is often claimed that xylitol
      is superior to the other sugar alcohols for caries control. This paper examines
      clinical studies on the caries-preventive and therapeutic effects of sugar
      alcohols with emphasis on sorbitol and xylitol. It is concluded that chewing
      sugar-free gum 3 or more times daily for prolonged periods of time may reduce
      caries incidence irrespective of the type of sugar alcohol used. It may be
      sufficient to do this only on school days. Sucking xylitol-containing candies or
      tablets may have a similar effect as chewing xylitol chewing gum. Clinical trials
      suggest greater caries reductions from chewing gums sweetened with xylitol than
      from gums sweetened with sorbitol. However, the superiority of xylitol was not
      confirmed in 2 out of 4 clinical trials comparing the caries-preventive effect of
      xylitol- with sorbitol-sweetened gums. The caries-preventive effects of polyol
      containing gums and candies seem to be based on stimulation of the salivary flow,
      although an antimicrobial effect cannot be excluded. There is no evidence for a
      caries-therapeutic effect of xylitol. These conclusions are in line with those of
      recent reviews and with the conclusions of the Scientific Committee on Medicinal
      Products and Medical Devices of the EU Commission.

PMID- 15153703
TI  - Are we ready to move from operative to non-operative/preventive treatment of
      dental caries in clinical practice?
AB  - This review focuses on the clinical interactions between patients and the dental
      team, not on caries prevention at a public health level. Many dentists no longer
      take a narrow surgical view seeking to apply interventive treatment as a one-off
      event at a certain trigger point of disease severity and the evidence that caries
      is an initially reversible, chronic disease with a known multi-factorial
      aetiology is being appreciated more widely. The caries process should be managed
      over time in an individualized way for each patient. Very few individuals can be
      considered to be truly 'caries free' when initial lesions as well as more
      advanced dentine lesions are considered. It is now very clear that, by itself,
      restorative treatment of the disease does not 'cure' caries. The caries process
      needs to be managed, in partnership with patients, over the changing challenges
      of a lifetime. The answer to the question posed in the title should be, in many
      cases, that we are ready to move to non-operative/preventive care (if we have not
      done so already). However, this should be for appropriate stages of lesion extent
      and in patients who respond to advice on recall frequency and preventive
      behaviours.

PMID- 15153704
TI  - How 'clean' must a cavity be before restoration?
AB  - The metabolic activity in dental plaque, the biofilm at the tooth surface, is the
      driving force behind any loss of mineral from the tooth or cavity surface. The
      symptoms of the process (the lesion) reflect this activity and can be modified by
      altering the biofilm, most conveniently by disturbing it by brushing with a
      fluoride-containing toothpaste. The role of operative dentistry in caries
      management is to restore the integrity of the tooth surface so that the patient
      can clean. Thus, the question, 'how clean must a cavity be before restoration?'
      may be irrelevant. There is little evidence that infected dentine must be removed
      prior to sealing the tooth. Leaving infected dentine does not seem to result in
      caries progression, pulpitis or pulp death. However, some of the bacteria
      survive. What is their fate and if they are not damaging, why is this?

PMID- 15153705
TI  - The future role of a molecular approach to pulp-dentinal regeneration.
AB  - The ultimate goal of a regenerative pulp treatment strategy is to reconstitute
      normal tissue continuum at the pulp-dentin border, regulating tissue-specific
      processes of tertiary dentinogenesis. Experimental investigations in mature teeth
      have shown that a network of extracellular matrix molecules and growth factors
      signal tertiary dentinogenesis. Application of dentin matrix components or growth
      factors in deep dentinal cavities stimulated up-regulation of biosynthetic
      activity of primary odontoblasts (reactionary dentin formation). Pulp-capping
      studies with a broad spectrum of biological agents, including growth factors and
      extracellular matrix molecules, showed formation of osteodentin and/or tertiary
      dentinogenesis (reparative dentin formation). Promising biologically active
      substances should be subjected to careful evaluation in well-designed preclinical
      investigations as well as in long-term clinical trials before their introduction
      in clinical practice.

PMID- 15153706
TI  - Getting research into clinical practice - barriers and solutions.
AB  - The success of current efforts towards evidence-based health services in many
      countries depends on efficient transfer of research findings to health
      practitioners. However, there is a lag in research being adopted. In part this is
      due to difficulties in interpreting or generalising research findings, in part to
      inertia, organisational structures and information. Clinical guidelines are
      usually cited as being the most effective product of evidence assessment and
      means of getting research into practice. The processes by which they are prepared
      and disseminated are discussed. Current clinical practice requires that health
      professionals adapt to changing systems and adopt new techniques. Therefore, in
      future, practice research to evaluate (a) clinical interventions and (b)
      dissemination and implementation strategies will become increasingly important.
      Recognised barriers to such research include lack of interest, lack of
      involvement, lack of time and lack of remuneration. High-quality research in
      dental primary care requires academics and dental service providers working in
      partnership on topics that are relevant both to clinicians and policy makers.
      Good project management, education and training are essential.

PMID- 15153707
TI  - Plasma ionized magnesium levels in neonatal respiratory distress syndrome.
AB  - Measurement of ionized magnesium (IMg) provides an accurate assessment of the
      free form of Mg, which is the physiologically active form and is most reflective
      of the biologically active and not easily measurable intracellular Mg fraction.
      Plasma levels of IMg were measured by ion-selective electrode method in premature
      newborns with respiratory distress syndrome (RDS), and relationships and
      correlations between IMg levels and various demographic, prognostic and
      laboratory characteristics were investigated by comparing the premature newborns
      with (study group; n = 19) and without RDS (control group; n = 20) in the present
      study. The values of the postnatal arterial pH and base excess and plasma IMg
      levels were significantly different between the study and control groups, and the
      number of newborns with any morbidity was significantly higher in the study
      group. Within the study group there were significant negative correlations
      between the plasma IMg levels and the values of the umbilical cord arterial pH (r
      = -0.621, p = 0.005) and base excess (r = -0.746, p = 0.001), and the value of
      the postnatal arterial base excess (r = -0.585, p = 0.008). The newborns who died
      later had higher plasma IMg levels than those who survived (0.89 +/- 0.45 vs.
      0.63 +/- 0.24 mmol/l, p = 0.026). These findings suggest that increase of plasma
      IMg may be due to extracellular movement of Mg, which is a principally
      intracellular ion, as a result of acidosis, hypoxia and probable cellular injury
      during the early course of RDS. The exact pathophysiological mechanism
      responsible for IMg increase, and whether determination of plasma IMg level,
      including umbilical cord blood IMg measurement, can be used as an early or
      predictive indicator of RDS in the diagnosis remain to be determined in further
      large-scale studies.

PMID- 15153708
TI  - Increasing incidence of critical liver disease among causes of death in Japanese
      hemophiliacs with HIV-1.
AB  - Critical liver diseases are now major causes of death in HIV-1-infected patients
      after the remarkable improvement in the clinical status resulting from highly
      active antiretroviral therapy. We report the results of an analysis on causes of
      deaths related to liver diseases based on our surveillance of hemophiliacs
      infected with HIV-1 up until May 31, 2002. A total of 1,405 patients (hemophilia
      A, 1,084, and hemophilia B, 321) were registered. The cumulative number of deaths
      was 534 (hemophilia A, 414, and hemophilia B, 120) by May 31, 2002. Hepatic
      disease due to HCV infection was found in 29.8% (95% confidence interval: 20.3
      40.7%) of the total cases with known causes of death after 1997, whereas this
      value was 14.0% (95% confidence interval: 10.8-17.7%) before 1997 (p < 0.01). We
      observed an increasing incidence of critical hepatic diseases among HIV-1
      infected hemophiliacs, thus suggesting that treatment of HCV infection is
      essential for HIV-1-infected hemophiliacs.

PMID- 15153709
TI  - Treatment of resistant/relapsing chronic lymphocytic leukemia with a combination
      regimen containing deoxycoformycin and rituximab.
AB  - BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) are sometimes
      resistant to treatment or relapse soon after the administration of the currently
      available frontline therapy including chlorambucil-prednisolone CHOP and
      fludarabine. We report the beneficial effect of an alternative chemotherapeutic
      regimen containing 2'-deoxycoformycin (pentostatin) and the monoclonal antibody
      anti-CD20 (rituximab) in 5 patients with resistant/relapsing CLL. PATIENTS: Five
      patients (4 men and 1 woman) with CLL at stage C, according to Binet's
      classification, were included in the therapeutic protocol. The median age of the
      patients was 76 years (range 57-84 years). Previous treatment consisted of
      chlorambucil-prednisolone, fludarabine, and CHOP. The current regimen comprised
      six 2-week cycles of pentostatin, 4 mg/m(2) i.v., combined with four cycles of
      rituximab, in a dose of 375 mg/m(2), every other week. RESULTS: Three patients
      responded to therapy, 2 achieved complete remission and 1 a partial response. Two
      patients did not respond to treatment. Toxicity was mild and well tolerated. The
      median survival duration of the responders was 19 months. These promising results
      suggest that salvage therapy with a combination regimen including pentostatin and
      rituximab may have a beneficial effect in patients with resistant/relapsing CLL.

PMID- 15153711
TI  - Canine long-term bone marrow culture neutrophil production and functionality.
AB  - This in vitro study has been conducted to determine the optimal experimental
      conditions under which to produce canine neutrophils in long-term bone marrow
      cultures (LTBMC), establish functional parameters of neutrophils obtained from
      LTBMC and peripheral blood and to ascertain whether these cells display
      physiological similarities. Our aim is to provide an experimental model, enabling
      a correlation between hemopoietic injury and neutrophil functionality. The
      authors demonstrate for the first time that canine neutrophils grown in cultures
      are able to produce oxyradicals capable of killing bacterial products. Moreover,
      culture-grown neutrophils contain gelatinase granules, a marker of terminal
      neutrophil differentiation, and express a specific surface antigen. The results
      described in this article illustrate the development of a dynamic system that
      mimics physiological hemopoiesis.

PMID- 15153710
TI  - Treatment of beta-thalassemia patients with recombinant human erythropoietin:
      effect on transfusion requirements and soluble adhesion molecules.
AB  - The most common single genetic disorder and a major public health issue in Greece
      and other Mediterranean countries is beta-thalassemia. Current therapeutic
      approaches for homozygous beta-thalassemia entail blood transfusions and iron
      chelation therapy with deferoxamine or deferiprone for preventing tissue
      hemosiderosis. Recently, much effort has focused on various inducers of fetal
      hemoglobin (HbF) such as recombinant human erythropoietin (rHuEPO), especially in
      beta-thalassemia intermedia. Ten adult patients, 5 with beta-thalassemia major
      and 5 with beta-thalassemia intermedia, received 150 IU/kg rHuEPO (epoetin-alpha)
      subcutaneously three times a week. Seven patients were transfused every 14-30
      days and 3 with beta-thalassemia intermedia were only occasionally transfused.
      The minimum duration of treatment was 12 weeks in order to define if there was
      any response. Transfusion intervals were modified according to the rHuEPO
      response to maintain stable Hb values. Lower transfusion requirements were
      observed in 5 patients after rHuEPO treatment (p = 0.028). In the 3 non
      transfused patients, Hb values increased, and the patients are still being
      treated and followed up for a period ranging from 14 weeks to 2 years. Two
      patients with thalassemia major discontinued treatment after 12 weeks, as they
      did not achieve any response regarding transfusion requirements or Hb values.
      Pretreatment serum transferrin receptor levels were higher than in controls (p <
      0.001) and significantly increased following rHuEPO treatment (p = 0.027).
      Patients had higher serum endothelin-3, sICAM-1 and sE-selectin values before
      rHuEPO treatment compared to controls (p < 0.001, p < 0.001 and p = 0.016,
      respectively), but these values were not altered during treatment. HbF values
      presented a slight, non-significant increase. rHuEPO treatment has a beneficial
      effect in transfusion-dependent beta-thalassemia patients. Although a slight
      increase in HbF levels was observed, other possible mechanisms are probably
      involved. None of our patients experienced thrombotic complications and a rise in
      blood pressure.

PMID- 15153713
TI  - Hematologic manifestation of childhood celiac disease.
AB  - We wanted to describe the hematologic manifestations of celiac disease (CD) in
      childhood. This study included 22 children with CD in whom the disease remained
      undiagnosed until they had presented with hematological abnormalities, such as
      anemia, thrombocytopenia, leukopenia or prolonged prothrombin time (PT) and
      activated partial thromboplastin time (APTT). Anemia was present alone in 19
      (86.3%) patients, and leukopenia coexisted with anemia in 2 (9%) patients.
      Thrombocytopenia was found alone in 1 (4.5%) patient. Twelve patients had an iron
      deficiency anemia. Iron deficiency coexisted with zinc and vitamin B(12)
      deficiency in 3 patients, copper and vitamin B(12) deficiency in two, vitamin
      B(12) deficiency in two, zinc deficiency in two and one patient had combined
      iron, zinc, and copper deficiency. Males had significantly lower values of
      hemoglobin (p < 0.05) and MCV (p < 0.05) compared to the females. In conclusion
      CD should be included in the differential diagnosis in children who present with
      anemia, leukopenia, thrombocytopenia or prolonged PT and APTT, especially in
      geographical areas where the prevalence of the CD is high.

PMID- 15153712
TI  - Molecular analysis of beta-thalassemia and sickle cell anemia in Antalya.
AB  - We have studied 918 chromosomes for mutations leading to beta-thalassemia and
      sickle cell anemia, which are the two most frequently found monogenic disorders
      in Antalya, Turkey. Three hundred and seventy-seven postnatal and 82 prenatal
      cases were studied between 2000 and May 2003 in our center using reverse dot blot
      hybridization (RDBH) with 22 probes specific for Mediterranean populations. In
      this study, IVSI-110 (G-->A) appeared to be the most common mutation with an
      occurrence rate of 44.4% among the 16 different mutations found to be associated
      with beta-thalassemia. Heterozygosity for IVSI-110 was the most prevalent
      combination, whereas 34 of our 377 postnatal cases showed homozygosity for this
      mutation, a genotype leading to beta-thalassemia major. The total percentage of
      postnatal patients clinically diagnosed as beta-thalassemia major was 18.6%,
      whereas 5% of the cases were diagnosed clinically as beta-thalassemia intermedia.
      One new Hb variant, Hb Antalya, and one new mutation, Cod 3 (+T) were found. HbS
      accounted for 10.3% of all mutations; homozygosity was found in 1.9% of all
      cases. Of the 82 cases analysed prenatally for beta-globin gene mutations and by
      cytogenetic techniques for possible chromosomal abnormalities, 21 fetuses were
      found to be affected with beta-globin gene mutations. One of these fetuses was
      also found to have a 45,X karyotype, and 1 had a 46,XY/47,XY,+22 karyotype. Quite
      a high rate of consanguineous marriages in Antalya (35.17%) renders mutation
      screening, genetic counseling, and educational programs held by our Thalassemia
      Unit essential. This study was the first to be performed specifically in our
      region where hemoglobinopathies are most frequent as a consequence of migrations
      of racially and culturally distinct groups to the area in the distant past.

PMID- 15153715
TI  - Treatment of a patient with chronic immune thrombocytopenic purpura with
      rituximab and monitoring by flow cytometric analysis.
AB  - Treatment modalities of patients with chronic immune thrombocytopenic purpura
      (ITP) include the administration of intravenous immunoglobulins (IVIG),
      corticosteroids, anti-D(Rh) immunoglobulin (anti-D), and splenectomy.
      Approximately 25-30% of patients with chronic ITP do not respond to established
      therapeutic regimens. We describe a 19-year-old patient with chronic ITP
      refractory to standard therapies treated with rituximab (anti-CD20 antibody).
      Initially, the therapy with rituximab appeared to be successful; however, the
      patient relapsed after a surveillance of 57 weeks documenting that the rituximab
      therapy has failed. Flow cytometric analyses during and after the administration
      of rituximab revealed new aspects of monitoring rituximab therapy.

PMID- 15153714
TI  - HLA antibodies and neonatal alloimmune thrombocytopenia.
AB  - A female baby with a severe thrombocytopenia at 18 x 10(9)/l was born to a 29
      year-old (gestation 2/partum 2) mother. Scattered petechiae were present on her
      legs, arms, chest and face, but there was no bleeding, infection, fever or
      hepatosplenomegaly. A platelet antibody screening immunocapture test was
      positive, which was performed on the mother's serum 3, 12 and 38 days after
      delivery, but no platelet-specific antibodies were found by the monoclonal
      antibody-specific immobilization of platelet antigen assay. The baby's platelets
      and lymphocytes and the father's platelets reacted strongly with the HLA
      antibodies present in the mother's serum. The neonate was treated with
      intravenous human immunoglobulin (Tegeline), 1 g/kg per day) 1, 2 and 3 days
      after delivery. The platelet count rose from 18 x 10(9)/l on day 0 to 37 x
      10(9)/l on day 3 and to 227 x 10(9)/l on day 12. No platelet transfusion was
      needed. Several factors which developed hereafter lead us to think that this
      neonatal alloimmune thrombocytopenia is due to the transplacental passage of
      maternal HLA antibodies to the baby.

PMID- 15153716
TI  - T cell receptor delta-chain gene rearrangement in a novel case of adult NK cell
      leukemia.
AB  - Malignancies arising from natural killer (NK) cells are being increasingly
      recognized as distinct clinicopathological entities. We here report the
      characteristics of a peculiar case of NK-cell acute leukemia with unusual
      agranular morphology and rearrangement of the T-cell receptor (TCR) delta-chain
      gene.

PMID- 15153717
TI  - Fludarabine combination regimen severely affected peripheral blood stem cell
      mobilization.

PMID- 15153718
TI  - Methotrexate-induced leukoencephalopathy reversed by aminophylline and high-dose
      folinic acid.

PMID- 15153719
TI  - Neutrophilic leukemoid reaction as the presenting feature of de novo and therapy
      related acute leukemias.

PMID- 15153720
TI  - The importance of platelet indexes in discriminating between beta-thalassemia
      trait and iron deficiency anemia.

PMID- 15153721
TI  - Automated analysis of bone marrow reticulocytes using the XE-2100 automated
      hematology analyzer.

PMID- 15153722
TI  - Is neoadjuvant hormonal therapy before radical prostatectomy indicated?
AB  - INTRODUCTION: Despite the success of surgical monotherapy in treating patients
      with organ-confined disease, nearly half of all patients undergoing radical
      prostatectomy will be pathologically upstaged on evaluation of the operative
      specimen. One possible means of improving the proportion of patients with organ
      confined disease and cancer-negative margins at surgery is implementing
      neoadjuvant androgen deprivation therapy. Studies evaluating the use of
      neoadjuvant hormonal therapy (NHT) before radical prostatectomy will be reviewed,
      and outcomes will be discussed. METHODS: Review of the past and recent literature
      regarding the use and role of NHT before radical prostatectomy was performed. In
      particular, special attention was paid to the seven prospective, randomized
      studies that have been reported in the literature. In addition, review of other
      pertinent and appropriate texts and journals regarding the impact of hormonal
      therapy on histopathological evaluation and outcomes was performed. RESULTS: Upon
      review of the prospective, randomized, clinical trials of NHT before radical
      prostatectomy, there remains no clear evidence that NHT improves disease-free
      survival for any stage of prostate cancer. Although positive surgical margins
      appear to be reduced for patients with clinical stage T2 disease only,
      significance and validity of such an end point remain uncertain. In addition, the
      use of NHT appears to come with a significant cost with regard to financial
      expense, patient morbidity, and possibly increased surgical difficulty.
      CONCLUSIONS: The routine use of NHT before radical prostatectomy is not
      justified, and only in controlled investigational trials should its use be
      considered.

PMID- 15153723
TI  - Urethral reconstruction after total penectomy for urethral cancer.
AB  - A 59-year-old white man developed a ventral ulcer with irregular limits in the
      middle portion of the penis. The result of the pathologic analysis was compatible
      with invasive squamous cell urethral carcinoma. A total penectomy was performed.
      In these cases, the usually recommended urinary diversion is perineal
      urethrostomy. However, due to the specifications of the case, perineal
      urethrostomy could not be performed. The literature did not offer any other
      alternative for patients with this same condition. Therefore, a urethral
      reconstruction using a groin skin flap had to be performed.

PMID- 15153725
TI  - Importance of serum p53 antibodies during follow-up after treatment of invasive
      bladder tumors.
AB  - INTRODUCTION: To investigate the prognostic importance of the changes in serum
      p53 antibody titrations during follow-up of patients who had anti-p53 antibody
      positive invasive bladder tumors with transitional epithelial cells. MATERIALS
      AND METHODS: The study group consisted of 23 clinically T3</=, N0, M0 patients
      with positive serum anti-p53 antibodies before treatment. 23 cases with negative
      serum anti-p53 antibodies who were comparable in age, comorbidity and stage with
      the study group were selected as a control group. The cases whose serum anti-p53
      titrations decreased to normal levels after treatment were compared for
      metastases, death rates and survival with cases who remained serum anti-p53
      positive and those who were serum p53 antibody-negative before treatment. Serum
      anti-p53 antibody titration was determined by ELISA. RESULTS: While serum anti
      p53 antibody titrations became negative in 8 (35%) of the 23 seropositive
      patients, it did not change in 15 patients (65%). There was a correlation between
      the maintenance of seropositivity, local progression/metastasis and death (p <
      0.05). Survival was found to be better in cases who were seronegative after
      treatment compared with cases who remained positive and also those who were
      seronegative before treatment (p < 0.05). CONCLUSION: The normalization of serum
      anti-p53 antibody positivity after treatment of invasive bladder tumors seems to
      be a good and reliable prognostic indicator.

PMID- 15153724
TI  - Adjuvant intravesical mitoxantrone versus recombinant interferon-alpha after
      transurethral resection of superficial bladder cancer: a randomized prospective
      study.
AB  - OBJECTIVE: To determine the efficacy and safety of two different doses of
      intravesical mitoxantrone and of recombinant interferon-alpha (IFNalpha-2b),
      instilled after transurethral resection (TUR) of superficial transitional cell
      carcinoma (TCC) of the bladder. MATERIAL AND METHODS: 208 patients (mean age
      62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder
      cancer were randomly allocated into four groups, after TUR of all visible tumors.
      Group A (45 patients) received no further therapy; group B (56 patients) received
      10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54
      patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and
      group D (53 patients) received 100 MU of IFNalpha-2b (8 weekly, 8 fortnightly and
      6 monthly instillations). RESULTS: During the follow-up (mean 21.09 months), 29
      (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group
      B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005).
      Furthermore, the differences in simple recurrence rates were statistically more
      significant (p < 0.05), when group A was compared with the three other groups in
      the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7,
      8, and 4 in groups A-D) experienced tumor progression, and the differences
      between the four groups were not statistically significant (p > 0.05). The mean
      recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C
      and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient
      months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1
      3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group
      D (p < 0.01). CONCLUSION: The two doses of mitoxantrone resulted in similar
      efficacy for the prevention of superficial bladder cancer recurrences, with the
      dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison
      with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of
      IFNalpha-2b showed a better combination of efficacy and safety.

PMID- 15153726
TI  - Association between mast cells and bladder carcinoma.
AB  - INTRODUCTION: The aim of this study was to determine whether there are
      quantitative variations in the numbers of mast cells (MCs) in bladder carcinoma
      tissue associated with the histopathological grading of tumours. MATERIALS AND
      METHODS: Specimens of 56 bladder carcinomas were stained with toluidine blue and
      histologically staged using the Mostofi system. The MC counts were assessed
      within tumour tissue and lamina propria of the bladder. The MCs in the adjacent
      'normal bladder tissue' of 14 specimens from patients who underwent cystectomy
      and of 10 specimens from patients having interstitial cystitis were also
      determined. The results were analyzed by using the Student t test, the Wilcoxon
      signed-rank test, and the Spearman correlation (r(s)). RESULTS: The mean MC
      concentration was 0.57 within the tumour tissue and 3.36 in the lamina propria.
      The difference between the two MC groups was statistically significant (p <
      0.0001); there were no correlations between mean MC counts in tumour tissue and
      histopathological tumour grade and between mean MC counts in lamina propria and
      histopathological tumour grade. Statistically significant differences were also
      observed between tumour group and interstitial cystitis group (p = 0.029) and
      between tumour group and normal 'adjacent' tissue group (p = 0.037). CONCLUSIONS:
      Our findings suggest that MCs aggregate in small numbers in the lamina propria of
      bladder carcinomas and that the MC count is related to tumour differentiation.
      The number of MCs may be a useful prognostic indicator in patients with bladder
      carcinoma.

PMID- 15153727
TI  - Relationship between complications due to prostate biopsy and the scores of pain
      and discomfort.
AB  - INTRODUCTION: Transrectal ultrasound (TRUS)-guided prostate biopsy is routinely
      performed in the prostate-specific antigen era. In this study, we evaluated
      morbidity and complications observed in patients undergoing TRUS-guided prostate
      biopsy following intrarectal lidocaine application and the relation of these
      complications to pain and discomfort. PATIENTS AND METHODS: Between January 2000
      and August 2002, a total of 128 patients underwent TRUS-guided prostate biopsy.
      The procedure was carried out following an intrarectal application of 10 cm(3) 2%
      lidocaine gel. Immediately after the biopsy, pain and discomfort scores were
      determined using a 10-point linear visual analog scale. The patients were seen 10
      days later and questioned for complications. RESULTS: At least one complication
      was observed in 107 patients (84%). Most frequent complications were macroscopic
      hematuria (90%), hematochezia (36%), and hematospermia (13%). The mean pain and
      discomfort scores of the patients were found to be correlated to each other (p <
      0.01). The complication-negative group had significantly lower pain and
      discomfort scores (p < 0.01). The scores of the patients with hematochezia were
      significantly higher than the scores of the patients with other complications (p
      < 0.01). CONCLUSIONS: Minor complications like hematuria, hematochezia, and
      hematospermia are frequently seen in patients undergoing TRUS-guided prostate
      biopsies. The pain and discomfort scores may be predictors of minor
      complications, particularly of rectal bleeding.

PMID- 15153728
TI  - Periprostatic lidocaine infiltration and/or synthetic opioid (meperidine or
      tramadol) administration have no analgesic benefit during prostate biopsy. A
      prospective randomized double-blind placebo-controlled study comparing different
      methods.
AB  - OBJECTIVES: To examine in a prospective, randomized, double-blind, placebo
      controlled study the analgesic effect of periprostatic nerve block and/or
      intravenous synthetic opioid administration during a 12-core prostate biopsy.
      PATIENTS AND METHODS: Patients were prospectively randomized to receive
      unilateral periprostatic lidocaine administration and/or intravenous synthetic
      opioid (meperidine or tramadol) administration. Placebo groups received sterile
      normal saline. Unilateral infiltration was performed and biopsy was begun on this
      side. The degree of pain was recorded using the visual analog scale/numeric
      analog scale (VAS/NAS) score before the procedure, during probe introduction into
      the rectum, during unilateral periprostatic nerve blockade, during the first 6
      core biopsy and during the second 6-core biopsy, and 30 min after biopsy
      completion. RESULTS: Most of the patients had mild or moderate pain (VAS/NAS <6)
      during the actual biopsy procedure. However, no significant differences existed
      between the groups with regard to the pain scores at any time (p > 0.05).
      Compared with pain scores, no significant differences existed between the first 6
      core (blocked side) and second 6-core biopsies (p > 0.05). CONCLUSION:
      Periprostatic lidocaine infiltration and/or intravenous synthetic opioid
      analgesics are not beneficial in significantly reducing pain during biopsy. We
      think that most of the patients do have pain during biopsy, however the intensity
      of pain is tolerable and does not require analgesics.

PMID- 15153729
TI  - The same-pedicle concept for continent urinary diversion using a Yang-Monti
      reconfigured tube.
AB  - OBJECTIVE: To facilitate the anastomosis of a continent valve to the umbilicus or
      a suitable skin area, we used a reconfigured tube made from the same segment of
      the intestinal reservoir as that used to construct the urinary pouch. MATERIALS
      AND METHODS: Seven patients underwent continent ileal-pouch formation using a
      reconfigured ileal tube following cystectomy for bladder cancer. Two irradiated
      patients and 1 patient with neurogenic bladder underwent continent colon-pouch
      construction with a reconfigured colon tube. RESULTS: The average length of the
      reconfigured ileal tube was 5 cm, while the colon tube was maximally 10 cm long.
      All procedures were technically straightforward. All the continent pouches
      functioned well, without catheterization difficulties. CONCLUSIONS: Since the
      Yang-Monti tube and the pouch are easily mobilized, being based on the same
      vascular pedicle, and can therefore bridge the gap, making the umbilical
      anastomosis was greatly facilitated. Sufficient support for the tube is provided
      by the pouch.

PMID- 15153730
TI  - Pubovaginal cutaneous fascial sling procedure for stress urinary incontinence: 10
      years' experience.
AB  - OBJECTIVES: There is a considerable lack of consensus regarding indications and
      long-term efficacy of the many techniques for treating urinary stress
      incontinence. We report the long-term results of a modified pubovaginal sling
      procedure. METHODS: From 1989 to 1998, 129 consecutive patients underwent a
      pubovaginal sling by two urologists. 86 of the subjects (67%) replied to a
      questionnaire designed to assess the outcome of the procedure and the subjective
      satisfaction with the operative result. During surgery we performed a modified
      sling procedure using a cutaneous strip strengthened by rectus fascia and placed
      with almost no tension. Special care was taken not to lacerate or damage but
      support the urethral musculature. We routinely did an anterior vaginoplasty, and
      posterior vaginoplasty if necessary. RESULTS: Mean patient age was 56.8 years,
      mean follow-up 39 months, mean parity 2.1, previous surgery 0.4. Improvement
      rates were determined as follows ('Are you satisfied with the operation?'):
      Significantly reduced incontinence (i.e. 50-100% improvement) was found in 65.2%,
      slight reduction (10-40% improvement) in 15.2%, no change in 17.4% and worsening
      in 2.2% of all 103 cases. The majority of all complications were wound
      infections. CONCLUSION: Despite the considerable failure rate, the substantial
      improvement in the quality of life of almost two thirds of the patients during a
      3-year follow-up recommends a pubovaginal sling as a treatment option for urinary
      incontinence.

PMID- 15153731
TI  - Tension-free vaginal tape and female stress incontinence: further evidence of
      effectiveness.
AB  - OBJECTIVES: Female stress incontinence is a frequent and distressing event with
      subsequent impact on quality of life. The tension-free vaginal tape (TVT)
      technique is considered to fulfill the criteria for an ideal surgical procedure
      and we therefore reviewed our cases to further analyze its effectiveness.
      MATERIALS AND METHODS: 57 patients suffering from stress incontinence with grade
      1-2 cystocele underwent the TVT operation. During follow-up (mean 22.2 months),
      the short- and long-term results were investigated. RESULTS: 91.3% of patients
      achieved complete resolution of previous stress incontinence in the early
      postoperative period. Early complications occurred in 8.7% of patients. Follow-up
      (mean 22.2 months) highlighted the stabilization of positive outcomes in 87.7% of
      cases. No postoperative modification of sexual habits and a significant
      improvement in quality of life were reported by all patients. CONCLUSION: The
      results of our study confirm that the TVT technique for stress incontinence is an
      easy to perform procedure which is safe, effective and long-lasting.

PMID- 15153732
TI  - Use of buccal mucosa patch graft for recurrent large urethrocutaneous fistula
      after hypospadias repair.
AB  - INTRODUCTION: To assess the effectiveness of buccal mucosa patch graft in the
      treatment of recurrent large urethrocutaneous fistula after hypospadias repair.
      MATERIALS AND METHODS: A free graft of buccal mucosa was used for closure in 7
      boys (mean age 4.8 years) with large (>4 mm) urethocutaneous fistula. Four
      fistulas were in the midshaft, 2 of them penoscrotal and 1 coronal type. All
      patients had undergone at least two previous unsuccessful fistula repairs, and 3
      of them had undergone three attempts for closure. Fistula repairs were similar in
      all cases. RESULTS: The repair was successful in 6 out of 7 cases, and in these
      cases the urinary stream was good after the removal of the catheter. The
      unsuccessful case was the coronal one. CONCLUSION: Based on our experience it
      seems that in cases with recurrent large fistula after hypospadias
      reconstruction, the use of buccal mucosa patch graft for closure is a good
      treatment choice.

PMID- 15153733
TI  - Seminal plasma prostate-specific antigen level in benign prostatic hyperplasia.
AB  - INTRODUCTION: We evaluated the role of the seminal plasma PSA level in the
      prediction of the response to alpha-blocker treatment in patients with benign
      prostatic hyperplasia. MATERIALS AND METHODS: 18 male patients with lower urinary
      tract symptoms were enrolled in the study. After their blood was sampled for PSA,
      ejaculates of all the subjects were obtained. Serum and seminal plasma PSA levels
      were calculated by Active PSA IRMA kit. Patients were given 4 mg/day doxazosin
      for a period of 6 weeks, following which their International Prostate Symptom
      Score (IPSS) evaluation was repeated. The correlation between serum PSA, seminal
      plasma PSA and PSA density levels and the percentage improvement in IPSS was
      investigated. RESULTS: The mean serum PSA level, the mean PSA density and the
      mean seminal PSA level of the patients were 2.7 +/- 1.2 ng/ml, 0.05 +/- 0.02
      ng/ml/cm(3) and 0.7 +/- 0.39 g/l, respectively. The percentage improvement in
      IPSS varied from 26.9 to 53.5%. Serum PSA and serum PSA density were not useful
      in the prediction of the response to alpha-blocker treatment, but the seminal PSA
      levels correlated with the percentage improvement in the IPSS (p = 0.017).
      CONCLUSIONS: Seminal plasma PSA has been found to be a better predictor of the
      response to alpha-blocker treatment when compared to serum PSA and PSA density.

PMID- 15153734
TI  - Silver nitrate sclerotherapy for 'clinically significant' chyluria: a prospective
      evaluation of duration of therapy.
AB  - OBJECTIVES: To evaluate and compare the results of regimen A (3 instillations at
      8-hourly intervals in 1 day) with the control regimen B (9 instillations at 8
      hourly intervals in 3 days) of using 1% silver nitrate solution for renal pelvic
      instillation sclerotherapy in 'clinically significant' filarial chyluria.
      MATERIALS AND METHODS: Forty-seven patients with clinically significant chyluria
      attending on 2 different days our urology clinic were prospectively randomized
      between two groups; the study group received regimen A (n = 21) while the control
      group received regimen B (n = 26). The variables evaluated included visualization
      of pyelolymphatic fistulae on retrograde pyelography, hospital stay, outcome and
      morbidity of the two regimens. RESULTS: Patients in both groups were comparable
      for age and sex. The morbidity (fever, symptomatic UTI, hematuria) following
      regimen A was less than that of regimen B although not statistically significant.
      The average hospital stay was 3 days for regimen A and 5.5 days for regimen B (p
      = 0.001). The initial success rate was 80.95% in group A and 92.30% in group B (p
      = 0.47). The mean duration of follow-up was 15 months (range 9-18). There was no
      significant difference in recurrence between the two groups during follow-up
      (group A: 21.05% and group B: 22.72%; p = 0.98). CONCLUSIONS: Regimen A was as
      effective as regimen B. Regimen A had the advantages of having less morbidity and
      shorter duration of hospital stay. We recommend only a 3-instillation regimen in
      patients with clinically significant chyluria, particularly those who demonstrate
      pyelolymphatic fistulae on retrograde pyelography.

PMID- 15153735
TI  - The experimental model of hydatidosis in rabbit testis. A preliminary study.
AB  - OBJECTIVES: Although no part of the human anatomy is invulnerable to hydatid
      disease, it has been reported to occur mostly in vital organs such as liver,
      lungs and brain. Hydatid disease of the urinary tract is uncommon accounting for
      only 2% of all such cases. Testes are extremely rare sites for echinococcosis. To
      our knowledge there are only 3 cases of testicular hydatid cyst described. In
      this animal model, we studied echinococcosis in rabbit testis. METHODS: We
      directly infected the unilateral testis of 4 male rabbits with infective
      protoscolices via intratesticular injection and housed them under pathogen-free
      conditions for 10 weeks. All rabbits survived during the follow-up period and
      then, at the 10th week, all testes were removed for histopathologic
      investigation. RESULTS: Despite of the direct infection of the rabbit testes with
      Echinococcus granulosus, there was no demonstrable hydatid cyst after a 10-week
      period except from some fibrosis in the injection tract of the testicular tissue
      in 1 case. CONCLUSION: The testes are extremely rare anatomic locations for
      echinococcosis infection. The mechanism of this resistance should be another
      reason apart from blood-testicular barrier. We think that low temperature in the
      scrotum or different properties of the testicular tissue may be the reasons of
      this defense mechanism. If this hypothesis clarifies with the further studies,
      new treatment options may be defined in the medical literature for the hydatid
      cyst.

PMID- 15153736
TI  - Simultaneous heterogenotypic renal cell carcinoma: immunohistochemical and
      karyoptic analysis by comparative genomic hybridization.
AB  - We report a rare collision tumor of a nodule-in-nodule pattern between a clear
      cell-type carcinoma and a collecting duct carcinoma in a 24-year-old man. Whereas
      the outer nodule is quite different from the 'conventional renal cell carcinoma
      (RCC)' with respect to vascularity, the inner nodule is quite distinctive as
      regards immunophenotype and karyotype results. Karyotyping the latter by means of
      comparative genomic hybridization (CGH) disclosed gains of chromosome regions in
      1q21.2-qter, 5q21-qter, 6q16.3-qter and 17q21.2-qter along with a loss in 1p21
      p31.14, 9q31-pter, 11, 13q12-qter, 15q12-qter and 18q21.1-qter. The clear cell
      carcinoma surrounding the daughter nodule revealed no 3p loss by means of CGH,
      unlike most cases of conventional RCC that are seemingly associated with poor
      vasculature. In summary, to our knowledge, this is the first reported case of an
      unclassified RCC featuring a unique growth pattern composed of a mixed clear cell
      type without a 3p loss and a variant of CDC with a unique karyotypic alteration.

PMID- 15153737
TI  - Hydronephrosis due to malrotation in a pelvic ectopic kidney with vascular
      anomalies.
AB  - A particular case of hydronephrosis in ectopic kidney due to a malrotation and
      vascular anomalies in a young girl is described. The patient was previously
      operated for ureteropelvic junction obstruction at the age of two. Clinic and
      radiographic and pathologic findings are discussed and the literature is
      reviewed.

PMID- 15153738
TI  - Delayed life-threatening haematuria from a renal pseudoaneurysm caused by blunt
      renal trauma treated with selective embolization.
AB  - Pseudo-aneurysms complicating blunt renal traumas, although very rare, represent
      significant causes of secondary haematuria, potentially life-threatening. Initial
      surgical repair of the injured kidney does not preclude the presence of an
      obscure pseudo-aneurysm that could become evident later on. We herein present a
      patient with a grade III blunt renal trauma initially treated surgically. Thirty
      days after the trauma, he developed secondary haematuria caused by a renal pseudo
      aneurysm located far from the oversewed area. This vascular lesion was
      successfully treated using selective arterial embolization.

PMID- 15153739
TI  - Mucinous metaplasia of the renal pelvic epithelium in a case of recurrent
      urolithiasis and pyelonephritis.
AB  - The occurrence of mucinous metaplasia of the renal pelvis in the absence of an
      associated malignancy is quite uncommon. We report a case of mucinous metaplasia
      of the renal pelvic epithelium without an associated squamous metaplasia in a 40
      year-old male with history of recurrent left renal calculi and urinary tract
      infections since the age of 10 years.

PMID- 15153740
TI  - Kidney transplants from living related donors having double inferior vena cava.
AB  - We performed four living related kidney transplantations from donors with double
      inferior vena cava (D-IVC), in which the left kidney was selected in two cases
      and the right in two cases. By dissecting the right internal iliac vein and
      isolating the right external iliac vein, the surgical procedure of the recipient
      side was so devised as to avoid any complications. In one patient, the surgical
      procedure of the donor side was modified to extend the donor left renal vein by
      anastomosis of part of the donor IVC to the renal vein. In the other case, no
      special treatment was necessary due to the patient's slender physique. In all
      four cases, transplants were successfully performed. The following conclusions
      can be made from these results: If the donor has D-IVC, it is essential to
      carefully conduct pre-operative examinations including angiography and venography
      to investigate other possible anomalies and blood flow of the renal vein. In
      addition, the graft must be carefully selected so that it is not disadvantageous
      to the donor. If there is no disadvantage to the donor as to which kidney is
      selected, the kidney with the longer renal vein should be transplanted.

PMID- 15153741
TI  - Asperger Syndrome, obsessive-compulsive disorder, and major depression in a
      patient with 45,X/46,XY mosaicism.
AB  - BACKGROUND: Although previous reports have described the association of autism,
      mental retardation, and schizophrenia with a missing Y chromosome, we are not
      aware of any case showing an association between this particular chromosomal
      abnormality and Asperger syndrome. METHOD: We report the case of a male patient
      with a combination of Asperger syndrome, obsessive-compulsive disorder and
      45,X/46,XY mosaicism. During the follow-up, this individual has also developed a
      severe episode of major depression, which was successfully treated with
      electroconvulsive therapy. RESULTS: To the best of our knowledge, this is the
      first case in which a 45,X/46,XY mosaicism was described in association with
      Asperger syndrome, either alone or associated with other psychiatric disorders.
      Diagnostic and therapeutic aspects of this unique case are presented and
      discussed. CONCLUSIONS: Our findings suggest that a missing Y chromosome may play
      an etiological role in some cases of Asperger syndrome.

PMID- 15153742
TI  - Classification of functional psychoses and its implication for prognosis:
      comparison between ICD-10 and DSM-IV.
AB  - BACKGROUND: The aim was to examine the agreement and differences between ICD-10
      and DSM-IV in the classification of functional psychoses. SAMPLING AND METHODS:
      In a sample of 218 first-hospitalised patients, ICD-10 diagnoses were compared
      with DSM-IV diagnoses. Functional psychoses of both diagnostic systems were
      classified into the four diagnostic groups schizophrenia, transient/episodic
      psychoses, delusional disorders and affective disorders. Based on information
      from a 15-year follow-up, it was examined which course is associated with each
      diagnostic group. RESULTS: Although in ICD-10 there was a higher frequency of
      schizophrenia and a lower one of affective disorders, a high agreement between
      ICD-10 and DSM-IV (kappa value of 0.82) was found. In both diagnostic systems,
      transient/episodic psychoses and affective disorders were mainly associated with
      a non-chronic course and schizophrenia was mainly associated with a chronic one.
      Nevertheless, several patients with transient/episodic psychoses showed a chronic
      course (ICD-10: 10%, DSM-IV: 15%) and more than one third of patients with
      schizophrenia a non-chronic one (ICD-10: 40%, DSM-IV: 33%). CONCLUSIONS: In the
      cross-sectional assessment, there is a high diagnostic agreement between ICD-10
      and DSM-IV. With respect to the long-term course, the delimitation of
      transient/episodic psychoses from schizophrenia was neither completely achieved
      by ICD-10 nor by DSM-IV.

PMID- 15153743
TI  - Deficit of executive functions in schizophrenia: relationship to neurological
      soft signs and psychopathology.
AB  - Cognitive deficits and neurological soft signs (NSS) have frequently been
      reported in schizophrenic patients and they both appear related to prominent
      negative symptoms. The aim of the present study was to examine the relationship
      between deficit of executive functioning, assessed by the Wisconsin Card Sorting
      Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to
      address the issue of whether a typology of schizophrenic patients may be
      identifiable by clinical, neurological and neuropsychological features. A sample
      of 26 male schizophrenic patients was divided, on the basis of the performance on
      the WCST, into two subgroups ('good performers' and 'poor performers') that were
      compared for the prevalence and severity of NSS, assessed by the Neurological
      Evaluation Scale (NES), and for the psychopathological features, assessed using
      the Positive and Negative Syndrome Scale (PANSS). To test for between-group
      differences, ANOVA was conducted. The 'poor performers' group showed greater
      severity of NSS: significant differences emerged for the NES total score and for
      the 'sequencing of complex motor acts' score. However, no significant differences
      between the groups emerged for any PANSS score. These findings seem to indicate
      that a common neurobiological abnormality could underlie cognitive deficits,
      especially concerning executive functioning, and subtle neurological
      abnormalities often present in schizophrenia, but they appear to deny that such
      dysfunctional correlates of schizophrenia are related to a prominent negative
      symptomatology.

PMID- 15153744
TI  - Endogenous, reactive and neurotic depression -- diagnostic stability and long
      term outcome.
AB  - BACKGROUND: No larger long-term study has been conducted of outcomes of patients
      diagnosed with endogenous, reactive or neurotic depression and using survival
      methods in the analyses. SAMPLING AND METHODS: All patients who had had their
      first-ever discharge in the period from 1970 to 1994 with a diagnosis of
      endogenous, reactive or neurotic depression according to ICD-8 were identified in
      a nationwide register of admissions to psychiatric wards. Patients were followed
      up to 1999 and the long-term diagnostic stability, the risk of relapse leading to
      readmission and the risk of suicide was analysed in the three groups. RESULTS:
      The diagnostic stability over time of the diagnosis of reactive depression and
      neurotic depression was low. Patients with neurotic depression had a
      substantially greater risk of relapse leading to readmission compared to patients
      with endogenous depression, and patients with reactive depression had less risk
      of relapse. No differences were found in the risk of completed suicide between
      the three groups of patients during long-term follow-up. CONCLUSIONS: The study
      does not provide evidence for re-establishing prior diagnostic systems of
      depressive disorders based on the presence or absence of neurotic characteristics
      or on the presence or absence of a psychic trauma as in ICD-8.

PMID- 15153745
TI  - Renin-angiotensin system gene polymorphisms: its impact on IgAN and its
      progression to end-stage renal failure among Chinese in Singapore.
AB  - BACKGROUND: Gene polymorphisms in angiotensin-converting enzyme (ACE),
      angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been
      associated with IgA nephropathy (IgAN) and its progression. Several studies on
      Caucasian and Japanese had reported contradicting results. We determined these
      polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess
      their clinical impact. METHODS: Genotyping was performed with DNA from peripheral
      leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes
      digestion, separation and identification of DNA fragments. Clinical data at renal
      biopsy and final status on renal function were determined from patients' records.
      RESULTS: Among controls, genotype distributions were in Hardy-Weinberg
      equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype
      distributions were similar whereas there was significant increase in the ACE DD
      genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF)
      and without (IgAN-nonESRF), there was no difference in any of the three gene
      polymorphisms. But in contrast, there were significant differences in higher male
      prevalence (p < 0.05), increased serum creatinine at presentation (p < 0.05),
      more sclerosis (p < 0.01) and higher tubulointerstitial lesion score (p < 0.001)
      in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene
      polymorphisms, only the DD genotype may predispose the individual to IgAN in our
      Chinese population. In contrast to clinical and histological risk factors, these
      genetic variations showed no impact on disease progression to ESRF. It is
      unlikely that genotyping more patients will prove these genes useful.
      Nevertheless, preclinically determined genetic markers are very useful as risk
      factors for disease occurrence and as prognostic indices for disease progression.
      Therefore, continuing efforts should be made to look at other genes to find those
      with significance.

PMID- 15153746
TI  - Water metabolism in rats subjected to chronic alcohol administration.
AB  - AIM: While the diuretic action of acute ingestion of alcohol has been studied
      extensively, the effect of chronic alcohol consumption has received less
      attention. The aim of the present study was to investigate the effect of chronic
      alcohol consumption on the balance of water intake and excretion and certain
      renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN:
      Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water
      (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats
      of each group during 7 days, at monthly intervals. In further experiments, the
      animals received a low-protein/high-fat diet with and without alcohol. RESULTS:
      When the rats were fed the standard diet, 24-hour urine excretion was
      significantly reduced in group A compared with group C. This difference was even
      more pronounced when the animals were fed the low-protein/high-fat diet. The
      reduced urine excretion was not due to lower liquid consumption and the pattern
      of daily excretion of faeces was comparable with that observed for urine
      excretion. Both sodium and potassium excretion and the diuretic response to an
      acute water load were significantly reduced in group A compared with group C. The
      changes in water balance induced by chronic alcohol consumption were reversible
      within a few days when the rats received water instead of 15% alcohol.
      CONCLUSIONS: Chronic alcohol consumption has an antidiuretic effect in rats. The
      percentage of total ingested fluid leaving the body as hidden water loss
      increases after alcohol consumption by up to 25-26% over control values.

PMID- 15153747
TI  - Chronic administration of bumetanide upregulates calbindin D28k mRNA and protein
      abundance in rat distal convoluted tubules.
AB  - BACKGROUND/AIMS: Calbindin D28k has been reported to be involved in transcellular
      calcium transport along the rat distal convoluted tubule (DCT). It has also been
      shown that administration of bumetanide is associated with hypercalciuria. The
      experiments reported here were designed to verify whether chronic infusion of
      this diuretic affects the gene expression and protein abundance of calbindin D28k
      along rat kidney DCT. METHODS: Bumetanide was subcutaneously infused by an
      osmotic minipump for 7 days at a rate of 1.5 mg x h(-1) x kg(-1). cDNA was
      synthesized from total RNA extracted from DCT microdissected from collagenase
      treated kidneys. RESULTS: Calbindin D28k mRNA abundance, quantified by
      competitive PCR, was found to be 13.7 +/- 1.9 amol x ng(-1) total RNA in DCT of
      control rats (n = 4) as compared to 24.2 +/- 2.4 amol x ng(-1) total RNA in DCT
      of bumetanide- treated rats (n = 5) (p < 0.01). This effect was associated with a
      52% increase (p < 0.005) in calbindin D28k protein abundance, as detected by
      Western blot performed on tissue slices from renal cortex (n = 4). CONCLUSION:
      These data not only demonstrate that bumetanide upregulates the mRNA and protein
      abundance of calbindin D28k in rat DCT, but also suggest that DCT calcium
      reabsorption is increased following the administration of this loop diuretic.

PMID- 15153748
TI  - Modulatory effect of the 23-kD calcium oxalate monohydrate binding protein on
      calcium oxalate stone formation during oxalate stress.
AB  - AIMS: To isolate, characterize, and quantify the 23-kD calcium oxalate
      monohydrate (COM) binding protein in the urine of controls and calcium oxalate
      stone formers and to study its role in kidney stone formation. METHODS: Calcium
      oxalate crystals were prepared and allowed to interact with human control kidney
      homogenate as well as urine of controls and calcium oxalate stone formers. EDTA
      extract was used for the separation of the 23-kD COM-binding protein (partially
      purified). This partially purified 23-kD COM-binding protein was further
      separated by DEAE-cellulose column chromatography. SDS-PAGE confirmed the
      molecular weight. An antibody was raised against the renal 23-kD COM-binding
      protein in rabbits. The 23-kD COM-binding protein was quantified in the urine
      from controls and stone formers by ELISA. Thiol group quantification, oxalate
      binding assay, and calcium oxalate crystal nucleation and aggregation were
      performed. Morphological changes of the calcium oxalate crystals induced by the
      urinary 23-kDa protein were determined using scanning electron microscopy. The
      expression of this protein using different concentrations of oxalate was also
      determined in an in vitro model. RESULTS: The urinary excretion of the 23-kD COM
      binding protein varies between 0.5 and 1.5 mg/24 h in controls, while in stone
      former its excretion was found to range from 5 to 7 mg/24 h. The protein isolated
      from urine was found to inhibit crystal nucleation and aggregation in controls,
      while the protein isolated from stone formers exhibited less inhibitory activity
      with reduced thiol groups. The 23-kD COM-binding protein derived from control
      urine formed COM crystals and intertwined calcium oxalate dihydrate crystals in a
      crystal growth system, while protein isolated from stone formers' urine induced
      aggregation of COM crystals. This protein expression was found to be increased
      with increasing concentration of oxalate in renal epithelial cells of the African
      green monkey kidney (VERO) cell line. CONCLUSIONS: Increased expression and
      excretion of the 23-kD protein was observed in oxalate stress conditions, and in
      stone formers this protein exhibited a promoting activity. The increased
      excretion of this protein with promoting activity favors the lithogenic process
      in stone formers.

PMID- 15153749
TI  - Urinary excretion rate of Tamm-Horsfall protein is related to salt intake in
      humans.
AB  - BACKGROUND/AIMS: Increased salt intake and enhanced salt sensitivity are
      implicated in the pathogenesis of hypertension. The aim of the present study was
      to investigate whether the urinary excretion rate of Tamm-Horsfall protein (THP)
      is dependent on salt intake in healthy, genetically hypertension-prone
      individuals. METHODS: Thirty unrelated subjects (13 men and 17 women, mean age
      48.1 +/- 6.7 years) with at least one first-degree relative with primary
      hypertension were studied. After a baseline investigation, the study subjects
      were put on a low-salt diet (10 mmol of sodium and 70 mmol of potassium per day)
      for 1 week. During the second week, sodium chloride capsules (230 mmol/day) were
      added to the diet to achieve a high-salt intake of 240 mmol/day. Urine samples
      (24-hour and overnight collections) were collected before the baseline
      investigation and at the end of the high- and low-salt diet weeks. The salt
      sensitivity was calculated as the difference between the blood pressure during
      high salt intake and the blood pressure during low salt intake. RESULTS: A low
      salt intake induced a decrease in the urinary excretion rate of THP during the
      night (11.7 microg/min) compared with baseline (19.5 microg/min; p < 0.05) and
      high salt intake (23.1 microg/min; p < 0.01). Furthermore, a greater response in
      blood pressure to a high salt intake, i.e. high salt sensitivity, was associated
      with increased excretion of THP in urine during the change to high salt intake (r
      = 0.38, p < 0.05). CONCLUSION: We were able to confirm that urinary excretion of
      THP is dependent on sodium intake. Patients with a high salt sensitivity, i.e. an
      exaggerated blood pressure response to high salt intake, responded to the high
      salt intake with an even greater increase in the urinary excretion rate of THP.
      The mechanism underlying this response is still unknown, but it might indicate
      that distal nephron function in healthy, genetically hypertension-prone
      individuals is altered.

PMID- 15153750
TI  - Perinatal food deprivation induces marked alterations of the hypothalamo
      pituitary-adrenal axis in 8-month-old male rats both under basal conditions and
      after a dehydration period.
AB  - Dehydration is a classic homeostatic stressor in rats that leads to a series of
      endocrine responses including stimulation of the hypothalamo-pituitary-adrenal
      (HPA) axis. During the last decade, it has been well established that perinatal
      food restriction is associated with the onset of diseases in adults. Our previous
      demonstration of long-term alterations in HPA axis activity in both basal
      conditions and after a 72-hour dehydration period in 4-month-old rats exposed to
      a 50% maternal food restriction (FR50) in late gestation and lactation prompted
      us to investigate whether such perinatal undernutrition further affects HPA axis
      activity in mature animals. As previously described in 4-month-old rats under
      basal conditions, 8-month-old FR50 rats showed reduced body weight and an
      enhanced ratio between mineralocorticoid receptor (MR) and glucocorticoid
      receptor (GR) mRNA levels in the hippocampus, as well as increased pro
      opiomelanocortin (POMC) mRNA levels in the adenohypophysis. In addition, numerous
      additional alterations appeared in mature rats. In the hypothalamus, levels of
      vasopressin (VP) mRNAs were increased both in the paraventricular nucleus (PVN)
      and in the supraoptic nucleus (SON). In the adenohypophysis, GR and prohormone
      convertase 2 (PC2) mRNA levels were significantly increased, whereas prohormone
      convertase 1 (PC1) mRNA was not affected by maternal undernutrition.
      Interestingly, undernourished animals exhibited high plasma levels of total and
      free corticosterone in spite of normal corticotropin (ACTH) levels, an indication
      that HPA basal activity is enhanced by maternal undernutrition in 8-month-old
      animals. Dehydration for 72 h induced a rise in ACTH plasma levels, but did not
      modify total and free corticosterone plasma levels in 8-month-old FR50 animals.
      In the adenopituitary, POMC mRNA levels were decreased after dehydration but PC1
      mRNA levels were unaffected. The present study indicates that maternal food
      restriction during the perinatal period dramatically affects the activity of the
      HPA axis until the age of 8 months. We speculate that higher basal HPA activity
      and an inadequate HPA response after dehydration in mature animals may contribute
      to diseases such as hypertension, known to develop with aging in perinatally
      growth-restricted rats.

PMID- 15153751
TI  - Mineralo- and glucocorticoid receptor mrnas are differently regulated by
      corticosterone in the rat hippocampus and anterior pituitary.
AB  - In most cell lines and animal tissues, glucocorticoid receptors undergo
      downregulation after exposure to corticosterone. However, corticosterone
      treatment has not shown a consistent effect on mineralocorticoid (MR) and
      glucocorticoid receptors (GR) in the hippocampus, and it has been rarely assessed
      in the anterior pituitary. In this study we investigated dose-dependent effects
      of corticosterone on MR and GR mRNAs in the hippocampus and anterior pituitary.
      Adrenalectomized rats substituted with corticosterone in drinking fluid were
      injected subcutaneously with vehicle or 1, 10, 50, 100, or 200 mg of
      corticosterone, and sacrificed 4 h later. In the hippocampus we found a
      progressive decrease in MR and GR mRNAs with increasing doses of corticosterone.
      This was significant with 50 and 100 mg corticosterone for MR mRNA and with 10
      200 mg corticosterone for GR mRNA at plasma corticosterone levels above 30
      microg/dl. The anterior pituitary did not show significant changes at any dose. A
      time-course with 2 mg of corticosterone (non-response dose range at 4 h) revealed
      a significant decrease in MR and GR mRNAs in the hippocampus 8 h after the
      subcutaneous injection. In the anterior pituitary both mRNAs showed an increase
      that was significant 24 h after injection for MR and from 8 to 24 h for GR. In
      the hippocampus, adrenalectomy (absence of corticosterone) induced a significant
      increase in MR and GR mRNAs on day 3, but not on days 1, 8 and 21 after
      adrenalectomy. In the anterior pituitary there were no significant changes at any
      time after adrenalectomy. In summary, we have found an in vivo corticosterone
      dose- and time-dependent downregulation of MR and GR mRNAs in the hippocampus,
      whereas anterior pituitary MRs and GRs seem relatively insensitive to the excess
      or the absence of corticosterone, suggesting the lack of an autoregulatory effect
      in this tissue. Significant mRNA changes appearing later in time could suggest a
      secondary response via a glucocorticoid-induced gene product. Corticosteroid
      receptor downregulation in the hippocampus could prevent overstimulation or
      tissue damage when plasma corticosterone is high, while increased corticosteroid
      receptors in the anterior pituitary could buffer the excessive brain drive on the
      pituitary during chronic stress or pathological conditions associated with
      increased plasma glucocorticoids, such as depression.

PMID- 15153752
TI  - Cloning of prodynorphin cDNAs from the brain of Australian and African lungfish:
      implications for the evolution of the prodynorphin gene.
AB  - In mammals the opioids Met-enkephalin and Leu-enkephalin are derived from a
      common precursor, proenkephalin, and as a result these neuropeptides are co
      localized in enkephalinergic neurons. The mammalian scheme for enkephalinergic
      networks is not universal for all classes of sarcopterygian vertebrates. In an
      earlier study, distinct Met- and Leu-enkephalin-positive neurons were detected in
      the central nervous system (CNS) of the African lungfish, Protopterus annectens.
      More recently, characterization of proenkephalin cDNAs separately cloned from the
      CNS of P. annectens and the Australian lungfish, Neoceratodus forsteri, revealed
      that the proenkephalin gene in these species encodes only Met-enkephalin-related
      opioids. In the current study a full-length prodynorphin cDNA (accession No. AY
      445637) was cloned and sequenced from the CNS of N. forsteri. In addition to
      encoding alpha-neoendorphin, dynorphin A and dynorphin B sequences unique to the
      lungfish, two Leu-enkephalin sequences, flanked by paired basic amino acid
      proteolytic cleavage sites, were detected in this precursor. The partial sequence
      of a P. annectens prodynorphin cDNA (accession No. AY445638) also encoded a Leu
      enkephalin sequence and a novel YGGFF sequence. The presence of the Leu
      enkephalin sequence in the lungfish prodynorphin precursors would explain the
      origin of the distinct Leu-enkephalin-positive neurons found in the African
      lungfish CNS. The realization that Met-enkephalin and Leu-enkephalin can be
      derived from distinct opioid-coding precursor genes calls into question the
      interpretation of comparative immunohistochemical studies that have mapped
      'enkephalinergic' networks in non-mammalian vertebrates.

PMID- 15153753
TI  - Mu opioid modulation of oxytocin secretion in late pregnant and parturient rats.
      Involvement of noradrenergic neurotransmission.
AB  - We have investigated effects of micro- and kappa-opioid agonists and antagonists
      on plasma oxytocin levels and noradrenaline content in the supraoptic nucleus
      (SON) and paraventricular nucleus (PVN) of 20-day pregnant rats. beta-Endorphin,
      oxytocin, estrogen and progesterone profiles in late pregnant and parturient rats
      were also sought. Stage of estrous cycle was monitored by vaginal smear, and pro
      estrous animals were left overnight with male. In the first set of experiments,
      pregnant rats were monitored and decapitated on days 20 and 21 and after the
      delivery of second pup. In the second set, 20-day pregnant rats were
      intracerebroventricularly infused with morphine (50 microg/10 microl), U50,488H
      (kappa-agonist; 50 microg/10 microl), clocinnamox (micro-antagonist; 50 microg/10
      microl) and norbinaltorphimine (kappa-antagonist; 50 microg/10 microl). Controls
      received saline alone. Serum estrogen and progesterone levels were measured by
      enzyme immunoassay, and plasma oxytocin and beta-endorphin by radioimmunoassay.
      Noradrenaline and its metabolite (3,4-dihydroxyphenylglycol) were determined in
      micropunched hypothalamic nuclei by HPLC-ECD. In parturient rats, oxytocin levels
      were increased (p < 0.05) and beta-endorphin decreased (p < 0.01) compared to 20
      day pregnant animals. Serum progesterone concentrations progressively declined
      towards parturition (p < 0.001). Clocinnamox raised oxytocin levels (p < 0.01)
      while U50,488H caused decreases (p < 0.05). Noradrenaline content was elevated by
      clocinnamox in the SON (p < 0.01) and PVN (p < 0.05) compared to control values.
      Other agonists and antagonists had no significant effect on the noradrenergic
      neurotransmission or oxytocin secretion. We suggest that noradrenaline may
      mediate the inhibitory effects of micro-opioids on oxytocin release. Our findings
      have also shown that kappa-opioid receptors are not involved in modulation of
      oxytocin neurons in late pregnant rats.

PMID- 15153754
TI  - Protein kinase Cdelta as gonadotropin-releasing hormone target isoenzyme in the
      alphaT3-1 gonadotrope cell line.
AB  - We investigated the kinetics of gonadotropin-releasing hormone (GnRH)-induced
      activation of the protein kinase C (PKC) delta isoform in alphaT3-1 gonadotrope
      cells. Results were evaluated in subcellular fractions and whole-cell lysates
      using specific antibodies recognizing either non- or (trans- and auto
      )phosphorylated forms of the kinase at Thr505 and Ser643 residues modulating
      stability and/or activation of the enzyme. Under basal conditions, and in
      contrast to PKC epsilon, PKC delta was mainly associated with the membrane
      compartment. GnRH (10(-7)M) elicited further and rapid membrane translocation and
      time-dependent phosphorylation at both sites of PKC delta. The neuropeptide's
      effects did not show a refractory period after short but successive GnRH
      stimulation and were abolished by the GnRH antagonist, antide. Sustained GnRH
      stimulation (2-6 h) provoked rapid down-regulation of PKC delta. Antide, by
      inhibiting the initial processes (translocation, phosphorylation), counteracted
      the degradation of the enzyme. Proteolytic processing of PKC delta was shown to
      mainly involve proteasome activity. Indeed, specific proteasome inhibitors
      prevented GnRH-elicited kinase depletion and induced membrane accumulation of the
      enzyme in a phosphorylated (Thr505, Ser643) form. Thus, GnRH may regulate time
      dependent cell responses by modulating the phosphorylation/activation state of
      its signal transduction effector proteins, and by maintaining their appropriate
      expression balance via proteolytic processes involving the proteasome system.

PMID- 15153755
TI  - Leptin stimulates growth hormone secretion via a direct pituitary effect combined
      with a decreased somatostatin tone in a median eminence-pituitary perifusion
      study.
AB  - The aim of this study was to examine the effect of recombinant human leptin on
      growth hormone (GH) secretion in perifused anterior pituitary slices from adult
      pigs. Anterior pituitary slices from sows were perifused and treated with
      recombinant human leptin (10 nM) and GH-releasing hormone (GHRH; 1 nM). In some
      experiments, pituitary slices were coincubated with stalk median eminence (SME).
      In a subset of the coincubation experiments, immunoneutralization of endogenous
      GHRH and somatostatin (SRIH) release was performed with antisera to GHRH and
      SRIH. Leptin increased GH secretion in pituitary slices alone (up to 100% vs.
      control at 40 min) as well as in pituitary slices coincubated with SME (up to
      122% vs. control at 40 min). A significant difference was observed in GH
      secretion from pituitary slices when the tissue was coincubated with leptin and
      GHRH at a low concentration (0.1 nM), but not when GHRH was used at 1 and 10 nM.
      Furthermore, anti-SRIH antiserum increased GH release from pituitary slices in
      coincubation experiments with SME. Finally, SRIH secretion was significantly
      reduced by leptin (down by 35% vs. control from 0 to 30 min of treatment) in
      cultured SME. These data show that leptin is effective in stimulating GH
      secretion by acting at two different levels: (1) it stimulates GH secretion
      directly from pituitary slices, and (2) it reduces SRIH tone from the median
      eminence and, indirectly, increases GH secretion from the pituitary. These
      results support the hypothesis that leptin may be an interesting hormonal
      mediator of growth and related metabolic effects by acting directly on the
      hypothalamic-pituitary axis.

PMID- 15153756
TI  - Changes of rat kidney AQP2 and Na,K-ATPase mRNA expression in lithium-induced
      nephrogenic diabetes insipidus.
AB  - BACKGROUND/AIM: In a rat model, lithium treatment is associated with polyuria and
      severe downregulation of aquaporin-2 (AQP2) protein in the inner medulla (IM) or
      in the whole kidney. However, it is not known (1) to what extent this
      downregulation occurs at the mRNA level; (2) whether the main sodium transporter
      of the nephron, Na,K-ATPase, is regulated in parallel at the mRNA level, and (3)
      whether lithium treatment induces zonal or segmental differences in AQP2 and Na,K
      ATPase mRNA levels. METHOD: We examined the changes in mRNA expression levels for
      AQP2 and Na,K-ATPase in kidney cortex, inner stripe of the outer medulla (ISOM),
      and IM of rats treated with lithium orally using semiquantitative Northern blot
      analyses and in situ hybridization at the light and electron microscopic levels.
      RESULTS: The AQP2 mRNA levels decreased significantly (p < 0.01) in lithium
      treated rats to 37 +/- 4% in the cortex, to 17 +/- 4% in the ISOM, and to 23 +/-
      5% in the IM, while the Na,K-ATPase mRNA levels were not altered in the cortex,
      but were significantly (p < 0.05) altered in the ISOM (144 +/- 15% after 10 days,
      but 68 +/- 4% after 4 weeks) and in the IM (63 +/- 8% after 10 days, but
      normalized after 4 weeks). In situ hybridization showed reduced levels of AQP2
      mRNA in all zones of the kidney, but the Na,K-ATPase mRNA expressions were
      slightly decreased only in IM collecting ducts. At the ultrastructural level,
      principal cells in the IM collecting ducts showed slight hypertrophy, but no cell
      damage after 4 weeks of lithium treatment. The results demonstrate substantial
      downregulation of AQP2 at the mRNA level throughout the collecting duct in
      experimental lithium-induced nephrogenic dabetes insipidus and moderately
      decreased Na,K-ATPase mRNA levels in the ISOM and in the IM. CONCLUSION: The
      results suggest that decreased mRNA expressions of AQP2 and Na,K-ATPase
      contribute to the development of lithium-induced nephrogenic diabetes insipidus.

PMID- 15153757
TI  - Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced
      diabetic kidneys.
AB  - BACKGROUND: Fractalkine is induced on activated endothelial cells and promotes
      strong adhesion of T cells and monocytes via its receptor CX3CR1. In kidney,
      fractalkine expression might be induced by high shear stress and play an
      important role in prolonged glomerular diseases. We examined whether fractalkine
      and CX3CR1 upregulation are found in streptozotocin-induced diabetic kidneys.
      METHODS: Diabetic rats were randomized to receive an angiotensin-converting
      enzyme inhibitor (temocapril), aminoguanidine or no treatment. Reverse
      transcription-competitive polymerase chain reaction, Western blot analysis and
      immunohistochemistry were used. RESULTS: At 4 weeks, fractalkine and CX3CR1 mRNA
      expression in diabetic kidneys increased compared with that in controls.
      Fractalkine staining in diabetic kidneys was clearly detected, along with
      glomerular capillary lumen and peritubular capillaries. A few CX3CR1 positive
      cell infiltration in diabetic glomeruli were found. Treatment with temocapril or
      aminoguanidine did not affect these changes. At 8 weeks, fractalkine and CX3CR1
      mRNA expression in untreated diabetic kidneys markedly increased compared with
      that in controls. Membrane-anchored fractalkine protein expression in untreated
      diabetic rats also increased. The increased expression was suppressed by the
      treatment with temocapril and aminoguanidine. Increased CX3CR1-positive cell
      infiltration in diabetic glomeruli was also inhibited by both treatments. Some
      CX3CR1-positive cells were ED3 positive. CONCLUSIONS: Fractalkine and CX3CR1
      upregulation were demonstrated in an early stage of diabetic kidney. These
      upregulation, as well as urinary albumin excretion, were suppressed by treatments
      with temocapril and aminoguanidine for 8 weeks. These findings suggest that
      fractalkine expression and CX3CR1-positive cell infiltration in diabetic kidneys
      might play an important role for progression of diabetic nephropathy.

PMID- 15153758
TI  - Bone morphogenetic protein-7 from serum of pregnant mice is available to the
      fetus through placental transfer during early stages of development.
AB  - BACKGROUND: BMP-7 is an important mediator of metanephric mesenchyme
      differentiation during kidney development. Gene knockout studies have shown that
      BMP-7 null mutation mice die shortly after birth due to renal failure, although
      the induction of metanephric structures has initially occurred (E11-E13).
      MATERIALS AND METHODS: Iodinated BMP-7 was injected into the tail vein of
      pregnant mice and its availability to tissues and fetuses was further analyzed by
      tissue uptake, LM autoradiography and SDS-PAGE electrophoresis. RESULTS: Studies
      on the distribution of 125I-BMP-7 injected through the tail vein of pregnant mice
      indicated that 125I-BMP-7 passed across the placenta and localized in developing
      fetal organs, in particular kidneys, up to day 14 of gestation. At later stages
      of pregnancy 125I-BMP-7 did not pass the trophoblasts of the placental barrier
      and did not enter the fetal blood vessels. CONCLUSION: The analysis of the
      distribution of 125I-BMP-7 from pregnant mice to fetal organs, in particular the
      kidney, suggests a cross-over of maternal circulating BMP-7 to the fetus through
      the placental barrier.

PMID- 15153759
TI  - Heparin-coated hemodialyzers--the holy grail for patients at risk of bleeding?

PMID- 15153760
TI  - Renal tumours in dialysis patients: who should we screen?

PMID- 15153761
TI  - Hemodialysis using heparin-bound Hemophan in patients at risk of bleeding.
AB  - BACKGROUND/AIMS: Since heparin can bind to Hemophan, hemodialysis using heparin
      bound Hemophan (HBH-HD) could be a useful modality in patients at risk of
      bleeding. We designed a simplified heparin binding technique and assessed the
      safety and efficiency of HBH-HD. METHODS: To bind heparin to Hemophan, heparin
      solution (1 liter, 20 IU/ml saline) was recirculated through Hemophan (GFS plus
      11, Gambro) for 1 h while the saline solution (700 ml/h) was removed. In 28
      maintenance dialysis patients at risk of bleeding, we evaluated the heparin
      concentration (HC) and activated partial thromboplastin time (aPTT) during HBH-HD
      to assess the increased risk of bleeding. We compared the safety and efficiency
      of HBH-HD with that of routine hemodialysis with low-dose heparinization (R-HD)
      in a prospective cross-over study, and then analyzed the outcomes of 1,057 HBH-HD
      in 159 patients. RESULTS: During HBH-HD, there was a slight increase in both HC
      (0.15 +/- 0.03 IU/ml, p < 0.01) and aPTT (43.7 +/- 5.7 s, p < 0.01) at 15 min
      after the initiation of dialysis compared to predialysis levels (0.11 +/- 0.03
      IU/ml and 37.5 +/- 6.3 s). However, there was no increase in HC and aPTT at 60
      min, 120 min and at the end of dialysis. In a cross-over study, aPTT during
      dialysis was markedly lower in HBH-HD than in R-HD (p < 0.01). The Kt/V (1.22 +/-
      0.31, p > 0.05) and urea clearance (136 +/- 17 ml/min, p > 0.05) of HBH-HD did
      not significantly differ from those of R-HD (1.29 +/- 0.57 and 136 +/- 13
      ml/min). However, the loss of total blood compartment volume of the dialyzer was
      greater in HBH-HD (17.5 +/- 9.2%, p < 0.01) than in R-HD (2.9 +/- 1.2%). Out of
      1,057 HBH-HD, 982 HBH-HD (93%) were successfully completed while 75 HBH-HD (7%)
      resulted in severe clotting. CONCLUSION: We conclude that the HBH-HD could
      minimize the bleeding risk and be an efficient HD technique in patients at high
      risk of bleeding. Careful observation for extracorporeal clotting is, however,
      required during HBH-HD.

PMID- 15153762
TI  - Present status of renal cell carcinoma in dialysis patients in Japan:
      questionnaire study in 2002.
AB  - AIMS: To determine the incidence and recent trends of renal cell carcinoma (RCC)
      in dialysis patients, a nationwide investigation was performed in Japan. METHODS:
      In February 2002, 3,155 questionnaires were sent to dialysis units in Japan. The
      variables studied for RCC diagnosed between March 2000 and February 2002 included
      patient age, duration of dialysis, diagnostic aids, cancer size, histology of
      cancer, and the presence of metastasis and acquired cysts. RESULTS: 489 RCCs (381
      males, 104 females, and 4 unknown) were studied. The mean age of the RCC patients
      was 57.5 +/- 11.4 (mean +/- SD) years, and the mean duration of dialysis was
      136.9 +/- 95.2 months. RCC was detected by symptoms alone in 5.3% of the cases,
      by sonographic screening in 46.1%, and computed tomographic screening in 44.2%.
      The metastasis rate was 15.2%. The standardized incidence ratio was 9.7 (95%
      confidence interval, CI: 8.3-11.2) for the male dialysis patients and 11.0 (95%
      CI: 8.2-14.4) for the female patients. Eighty-four of the RCC patients with more
      than 20 years of hemodialysis were younger, were more frequently male, and
      demonstrated a larger cancer size, a higher incidence of papillary RCC, a higher
      metastasis rate, and a higher incidence of fatal RCC than 215 patients with less
      than 10 years of dialysis. CONCLUSION: 54.6% of the patients with RCC received
      dialysis for more than 10 years. For RCC patients with more than 20 years of
      dialysis, the mean age was younger, and the metastasis rate was higher than for
      RCC patients with less than 10 years of dialysis.

PMID- 15153763
TI  - Safety and efficacy of sevelamer in the treatment of uncontrolled
      hyperphosphataemia of haemodialysis patients.
AB  - BACKGROUND/AIM: The treatment of hyperphosphataemia is of major importance in the
      management of patients on dialysis. Traditional phosphate binders can be
      associated with undesirable effects. Recently, a new non-absorbable phosphate
      binding polymer, sevelamer hydrochloride, has been available. Clinical
      information is scarce, and its cost could be a limiting factor for its wider use.
      No studies have evaluated its usefulness in uncontrolled hyperphosphataemic
      patients. METHODS: We identified 34 patients with a maintained serum phosphorus
      concentration >6.5 mg/dl and/or toxicity related to standard phosphorus-binding
      treatment (aluminium or calcium based). Sevelamer was added and titrated up
      fortnightly to achieve phosphorus control. Previous phosphate binders were
      decreased, whenever possible. The period of the study was 6 months. RESULTS:
      Thirteen patients (38%) dropped out because of side effects, mainly related to
      the gastro-intestinal tract. The efficacy analysis disclosed that the phosphorus
      concentration decreased from 2.39 +/- 0.48 to 1.84 +/- 0.48 mmol/l (p < 0.001).
      The mean dose of sevelamer was stabilised at 3.4 +/- 1.8 g/day. The amount of
      calcium- and aluminium-based phosphate binders could be decreased from 5.1 +/-
      3.5 to 3.1 +/- 2.7 g/day (38% decrease) and from 2.4 +/- 1.5 to 1.5 +/- 1.7 g/day
      (36% decrease), respectively. The Ca x P product was significantly decreased from
      5.83 +/- 1.19 to 4.36 +/- 1.12 mmol/l2 (p < 0.001). The total cholesterol
      concentration decreased from 4.34 +/- 0.9 to 3.98 +/- 0.9 mmol/l (p < 0.01) and
      the low-density lipoprotein cholesterol level from 2.61 +/- 0.98 to 2.20 +/- 0.77
      mmol/l (p < 0.03). CONCLUSIONS: Sevelamer is an effective phosphate binder that
      allows a better serum phosphorus control, while allowing a decrease in the dose
      of calcium- and aluminium-based phosphate binders in these difficult patients.
      The drawbacks are the high intolerance rate and the price of the product.

PMID- 15153764
TI  - Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in
      chronic hemodialysis patients: a 3-year prospective study.
AB  - BACKGROUND/AIM: Brain atrophy is known to develop more rapidly in hemodialysis
      (HD) patients than other individuals. The present study was designed to examine
      the role of HD-related hypotension in brain atrophy in patients on chronic HD.
      METHODS: By using magnetic resonance imaging, whole brain atrophy was assessed by
      the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal
      brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain
      area/intracranial frontal space). The number of lacunae was also counted. We
      studied 32 HD patients without symptomatic neurological abnormalities or diabetes
      mellitus: male/female ratio 19/13; mean age +/- SD 53 +/- 10 (range 28-77) years;
      mean HD duration +/- SD 11 +/- 6 (range 1-22) years. Magnetic resonance imagings
      were taken in 1995 and 1998. All dialysis-related hypotension episodes during the
      same period were identified from the medical records and counted. RESULTS: The
      VBR ranged from 8.8 to 18.7% in 1995 (12.8 +/- 2.2%) and was not different in
      1998 (13.1 +/- 2.7%). However, the VBR increased by more than 5% in 14 patients,
      and their HD duration of 13 +/- 6 years was significantly longer than that of 18
      patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 +/- 4.2% (range
      55.8-71.3%) and decreased significantly to 59.7 +/- 4.7% (range 50.2-70.9%) in
      1998 (p < 0.05). The change in FAI correlated significantly with both the total
      number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the
      increase in number of lacunae (r = 0.42, p < 0.05). CONCLUSION: Our results
      suggest that dialysis-related hypotension plays a role in progressive frontal
      lobe atrophy in HD patients.

PMID- 15153765
TI  - The bacterial cytoskeleton and its putative role in membrane vesicle formation
      observed in a Gram-positive bacterium producing starch-degrading enzymes.
AB  - Bacteria may possess various kinds of cytoskeleton. In general, bacterial
      cytoskeletons may play a role in the control and preservation of the cell shape.
      Such functions become especially evident when the bacteria do not possess a true
      wall and are nevertheless elongated (e.g. Mycoplasma spp.) or under extreme
      cultivation conditions whereby loss of the entire bacterial cell wall takes
      place. Bacterial cytoskeletons may control and preserve the cell shape only if a
      number of preconditions are fulfilled. They should be present not only
      transiently, but permanently, they should be located as a lining close to the
      inner face of the cytoplasmic membrane, enclosing the entire cytoplasm, and they
      should comprise structural elements (fibrils) crossing the inner volume of the
      cell in order to provide the necessary stability for the lining. Complete loss of
      the cell wall layers had earlier been observed to occur during extensive
      production of bacterial starch-degrading enzymes in an optimized fermentation
      process by a Gram-positive bacterium. Even under these conditions, the cells had
      maintained their elongated shape and full viability. Which of the various kinds
      of bacterial cytoskeleton might have been responsible for shape preservation?
      Only one of them, the primary or basic cytoskeleton turns out to fulfil the
      necessary preconditions listed above. Its structural features now provided a
      first insight into a possible mechanism of formation of membrane blebs and
      vesicles as observed in the Gram-positive eubacterium Thermoanaerobacterium
      thermosulfurogenes EM1, and the putative role of the cytoskeletal web in this
      process.

PMID- 15153766
TI  - Enhancement of translation initiation by A/T-rich sequences downstream of the
      initiation codon in Escherichia coli.
AB  - The region located downstream of the initiation codon constitutes part of the
      translation initiation signal, significantly affecting the level of protein
      expression in E. coli. In order to determine its influence on translation
      initiation, we inserted random 12-base sequences downstream of the initiation
      codon of the lacZ gene. A total of 119 random clones showing higher beta
      galactosidase activities than the control lacZ gene were isolated and
      subsequently sequenced. Analysis of these clones revealed that their insertion
      sequences are strikingly rich in A and T, but poor in G, with no consensus
      sequences among them. Toeprinting experiments and polysome profile analysis
      confirmed that the A/T-rich sequences enhance translation at the level of
      initiation. Collectively, the present data demonstrate that A/T richness of the
      region following the initiation codon plays a significant role in E. coli gene
      expression.

PMID- 15153767
TI  - Molecular genetic analyses of potential beta-galactosidase genes in Xanthomonas
      campestris.
AB  - Xanthomonas campestris pv. campestris, which displays no significant beta-1,4-D
      galactopyranosidase activity, has three annotated beta-galactosidase genes in the
      sequenced genome, designated galA, galB and galC herein. GalA and GalB are
      similar to glycosyl hydrolase (GH) family 2 enzymes, including Escherichia coli
      LacZ. galA and galB cannot express detectable activity even after being cloned in
      frame and driven by the vector's promoter. GalC is a GH35 enzyme homologous to
      the Xanthomonas axonopodis pv. manihotis Bga. The latter cleaves beta,1-3-linked
      galactose 1,000 times faster than beta,1-4-linked galactose and is not
      responsible for lactose utilization. In X. campestris pv. campestris cells, GalC
      is readily detectable by Western blotting, and the levels can be increased by
      cloning the gene under the control of the vector's promoter. Results of
      insertional mutation, transcriptional fusion assay and Western blotting indicated
      that galC, clustered with several GH genes, is cotranscribed with the upstream
      gene(s) and is expressed constitutively. Xc17L is a previously isolated mutant
      with elevated beta-galactosidase activity and a greatly improved ability to grow
      on lactose. Results of DNA sequencing of Xc17L galA, galB and galC, enzyme assays
      of galA, galB and galC mutants derived from Xc17L, and Western blotting of GalC
      in Xc17L indicated that the three beta-galactosidase genes do not encode the
      elevated beta-galactosidase activity in Xc17L. The presence of a fourth beta
      galactosidase gene is proposed.

PMID- 15153769
TI  - Analysis of fruE, a novel developmental gene of Myxococcus xanthus.
AB  - Myxococcus xanthus is a gram-negative soil bacterium that undergoes multicellular
      development upon nutrient starvation. In the present study, a TnV insertion
      developmental mutation, Omega773, of M. xanthus was analyzed. The TnV Omega773
      insertion was found to be located within a novel developmental gene, fruE. The
      FruE protein is composed of 140 amino acid residues and bears an N-terminal
      signal peptide. The amino acid sequence of FruE shared no significant similarity
      with any other known protein in the databases. The fruE mutant displayed a
      development-delayed phenotype. The formation of tightly aggregated mounds in the
      fruE mutant was slower than that in the wild-type strain. The initiation of spore
      production in the fruE mutant was delayed by 12 h in comparison to the wild-type
      strain, and the process of spore formation was more asynchronous than that of the
      wild-type strain. The transcription initiation sites of the fruE gene were
      located 81 bp (P1) and 57 bp (P2) upstream of the fruE initiation codon. Although
      both promoters were active during vegetative growth and development, the P1
      promoter was more active during development and the P2 promoter was more active
      during vegetative growth. The expression of the fruE gene increased to a peak at
      6 h poststarvation and then decreased. The decrease in fruE expression was not
      observed in the D and E signal mutants.

PMID- 15153768
TI  - Molecular characterization of the essential response regulator protein YycF in
      Bacillus subtilis.
AB  - The response regulator YycF is essential for cell growth in gram-positive
      bacteria including Bacillus subtilis, Staphylococcus aureus and Streptococcus
      pneumoniae. To study the function of YycF in the essential process, we
      characterized a YycF (H215P) mutation that caused temperature-sensitive growth in
      B. subtilis. The response regulators YycF and YycF (H215P) were analyzed using
      circular dichroism spectroscopy, whose T(m) values were 56.0 and 45.9 degrees C,
      respectively, suggesting that YycF (H215P) significantly affects the protein
      structure with an increase in temperature. Furthermore, using the gel mobility
      shift assay and DNase I footprinting, we investigated the effect of YycF (H215P)
      on binding to the YycF box of ftsAZ operon of B. subtilis. The replacement of the
      histidine 215 with proline resulted in a decrease of the DNA-binding ability of
      YycF in vitro. In vivo, using Escherichia coli two-hybrid and homodimerization
      assays, we clarified that His 215 of YycF plays a crucial role in the
      homodimerization of the protein. Thus the essential genes involved in growth of
      B. subtilis appear to be regulated by the homodimer of YycF. These results
      suggest that the YycF dimerization is an excellent target for the discovery of
      novel antibiotics.

PMID- 15153770
TI  - Heat shock (sigma32 and HrcA/CIRCE) regulons in beta-, gamma- and epsilon
      proteobacteria.
AB  - During heat shock, the main strategy of an organism is defense from denatured
      proteins. This is performed by chaperones that refold and proteases that cut
      abnormal proteins. In studying the sigma(32) and HrcA regulons in beta- and gamma
      proteobacteria, we have found some new potential participants in the heat shock
      response and proposed the protein disulfide isomerase function for one of them.
      We describe the connection between the two regulons through cross-regulation of
      the HrcA repressor and sigma(32) in some beta-proteobacteria. Finally, we predict
      the binding signal for HrcA in epsilon-proteobacteria.

PMID- 15153771
TI  - Lipopolysaccharide O-antigen antibody-based detection of the fish pathogen
      Flavobacterium psychrophilum.
AB  - Several yellow-pigmented species within the family Flavobacteriaceae are commonly
      associated with diseases in fish and are difficult to speciate due to their
      fastidious, slow-growing nature and cross-reactive antigens. Here we report the
      development of specific, antibody-diagnostic tests for Flavobacterium
      psychrophilum, the aetiological agent of rainbow trout fry syndrome and bacterial
      cold water disease. A unique antigen from F. psychrophilum, the
      lipopolysaccharide (LPS) O-polysaccharide (O-PS), formed the basis for the
      antibody test. LPS O-PS was purified and conjugated to keyhole limpet haemocyanin
      and bovine serum albumin for the generation of rabbit immune sera and the
      development of antibody-based diagnostic tests. Rabbit polyclonal anti-O-PS serum
      was highly specific for F. psychrophilum, without the need for prior cross
      absorption with related bacteria and was the basis of an effective ELISA
      diagnostic test. Antibodies were purified from rabbit anti-O-PS serum and
      adsorbed onto coloured latex beads for the development of a specific, bead
      agglutination assay for F. psychrophilum.

PMID- 15153772
TI  - Bioinformatic analyses of the bacterial L-ascorbate phosphotransferase system
      permease family.
AB  - The tripartite L-ascorbate permease of Escherichia coli is the first functionally
      characterized member of a large family of enzyme II complexes (SgaTBA, encoding
      enzymes IIC, IIB and IIA) of the bacterial phosphotransferase system (PTS). We
      here report bioinformatic analyses of these proteins. Forty-five homologous
      systems from a wide variety of bacteria were identified, but no homologues were
      found in archaea or eukaryotes. These systems fell into five structural types:
      (1) IIC, IIB and IIA are encoded by distinct genes; (2) IIC and IIB are encoded
      by distinct genes, but the IIA-encoding gene is absent; (3) IIC and IIB are
      encoded by a fused gene, but IIA is a distinct gene product; (4) IIA and IIB are
      fused, but IIC is encoded by a distinct gene, and (5) IIC and IIB are encoded by
      distinct genes, but IIA is fused to a transcriptional regulator. Phylogenetic
      analyses revealed that gene fusion/splicing events have occurred repeatedly
      during the evolutionary divergence of family members, although no evidence for
      shuffling of constituents between systems was obtained. The SgaTBA family proved
      to be distantly related to the GatCBA family of PTS permeases, and this family
      was also analyzed. In contrast to the SgaTBA family, no gene splicing/fusion has
      occurred during the evolutionary divergence of GatCBA family members as each
      domain is always encoded by a distinct gene. However, GatC homologues were
      identified in organisms that lack other PTS proteins, suggesting a transport
      mechanism not coupled to substrate phosphorylation. Topological analyses suggest
      that in contrast to all other PTS permeases, IIC proteins of the Sga and Gat
      families exhibit 12 transmembrane alpha-helical segments and are distantly
      related to secondary carriers. Like many secondary carriers, GatC (IIC)
      homologues could be shown to have arisen by an ancient intragenic duplication
      event. These results suggest that the Sga and Gat families of PTS permeases
      comprise a small superfamily in which the transmembrane IIC domains evolved
      independently of all other known PTS permeases.

PMID- 15153773
TI  - Divergent promoter organization may be a preferred structure for gene control in
      Escherichia coli.
AB  - The prokaryote possesses intriguing promoter arrangements called divergent
      promoters, which transcribe adjacent genes in opposite directions. The genome
      analysis in Escherichia coli revealed the occurrence of a large number of
      divergent promoters, whose total number was estimated to be about 1.6-fold larger
      than that of single promoters. Surprisingly, more than 65% divergent promoters
      transcribe functionally unrelated genes. Transcription from one promoter has been
      proposed and demonstrated to influence that from the other promoter via change in
      superhelicity in the divergent promoter region. Therefore, the organism may have
      acquired divergent promoters as a common structure for ingenious gene controls
      including transcription coupling.

PMID- 15153774
TI  - Eukaryotic promoters can direct protein synthesis in Gram-negative bacteria.
AB  - Intracellular bacteria can act as DNA delivery vectors into mammalian cells.
      Transfer of genetic information can be monitored by screening for cellular
      expression of a reporter gene under the control of an eukaryotic promoter.
      However, intracellular bacteria can also efficiently deliver heterologous
      proteins in the cell cytosol. We have studied the activity of the eukaryotic PCMV
      promoter in Escherichia coli and Salmonella typhimurium using the lacZ and gfp
      genes as reporters and determined its strength relative to those of PRSV and
      PSV40 in E. coli. We found substantial heterologous activity of fragments
      carrying the PCMV and PRSV promoters, the strength of PRSV being greater than
      that of PCMV, but did not detect any PSV40 activity in E. coli. The green
      fluorescent protein (GFP) synthesized in E. coli was transferred to COS-1 cells
      where it was detectable and stable. Insertion of a transcription terminator or
      deletion of the bacterial ribosome binding site downstream from PCMV led to the
      silencing of the promoter in bacteria but not in mammalian cells. These
      observations should incite to exert caution when interpreting data on the DNA
      transfer from bacteria to mammallian cells when the genes of interest are under
      the control of the PCMV or PRSV promoter.

PMID- 15153775
TI  - Alpha4beta1 integrin (VLA-4) blockade attenuates both early and late leukocyte
      recruitment and neointimal growth following carotid injury in apolipoprotein E (
      /-) mice.
AB  - BACKGROUND: The alpha(4)beta(1) integrin (VLA-4) supports rolling and firm
      adhesion of leukocytes to inflamed tissues via ligation of VCAM-1 or fibronectin
      expressed on the activated endothelium. We tested the hypothesis that VLA-4
      mediates leukocyte recruitment and neointimal growth after arterial injury in the
      atherosclerosis-prone apolipoprotein E (ApoE)-deficient mouse. METHODS: ApoE (-/
      ) mice fed a Western diet underwent air desiccation injury, and the expression
      patterns of VLA-4 and VCAM-1 were determined by immunohistochemistry (IHC). To
      determine the effect of targeted VLA-4 blockade on leukocyte recruitment and
      neointimal growth, ApoE (-/-) mice received an intraperitoneal injection of a VLA
      4 neutralizing monoclonal antibody (PS/2) at the time of injury alone or over a
      prolonged administration course. Additional mice received an isotype control
      antibody. RESULTS: IHC demonstrated a marked increase in VLA-4 expression 7 days
      following injury. Prolonged administration of PS/2 resulted in a 72% reduction (p
      < 0.02) in neointimal growth 28 days following injury. IHC revealed a marked 95%
      reduction in neutrophil recruitment at 7 days and a 48% reduction in macrophage
      recruitment 28 days following injury with prolonged PS/2 administration.
      CONCLUSIONS: Prolonged VLA-4 blockade reduces leukocyte recruitment and
      neointimal growth following air desiccation injury in ApoE (-/-) mice. These
      findings demonstrate an important role for VLA-4 in the response to arterial
      injury.

PMID- 15153776
TI  - Anodal current intensities above 40 microA interfere with current-induced axon
      reflex vasodilatation in human skin.
AB  - When using iontophoresis, the 'non-specific' vasodilatation (NSV) that is
      observed as a result of C-fibre excitation is generally attributed to the local
      accumulation of protons under the anode. NSV following prolonged 100-microA
      anodal current application only appears after the current is stopped. Break
      excitation alone does not explain the delayed onset of this vasodilatation. We
      hypothesised that this delay could result from an anodal block and thus, that a
      minimal intensity would be required to achieve hyperpolarisation of primary
      afferent fibres (mainly C-fibres). Using laser Doppler flowmetry, cutaneous blood
      flow was recorded in the forearms of 8 healthy volunteers 2 min before current
      application, during the application and 20 min after stopping the monopolar
      anodal current. In protocol 1, after 2.5 min of current application at an
      intensity of 100 microA, the intensity was abruptly decreased to 0-80 microA for
      a second 2.5-min period. The onset of vasodilatation was only delayed at
      intensities >30 microA during this second period. In protocol 2, re-application
      of the current after a 50-second interruption (expected to allow for the
      occurrence of an axon reflex) did not interfere with the onset of vasodilatation.
      Thus: (1) the minimal intensity interfering with the axon reflex is far lower
      than that reported for C-fibre blockade in isolated nerves; (2) the results
      suggest that current application does not directly interfere with the vasodilator
      mechanisms induced by the axon reflex at the level of smooth muscle cells.

PMID- 15153777
TI  - The role of CD40-CD154 interaction in cell immunoregulation.
AB  - CD40, a member of the nerve growth factor/tumor necrosis factor receptor
      superfamily, and its ligand, CD154, play essential roles in cell immune
      responses. The results of many studies have indicated that CD40-CD154 interaction
      can upregulate costimulatory molecules, activate antigen-presenting cells (APCs),
      influence T-cell priming and T-cell-mediated effector functions as well as
      participate in the pathogenic processing of chronic inflammatory diseases, such
      as autoimmune diabetes, graft rejection, atherosclerosis, and cancer. Ligation of
      CD40 on cancer cells was also found to produce a direct growth-inhibitory effect
      through cell cycle blockage and/or apoptosis with no overt side effects on normal
      cells and treatment with CD154 can heighten tumor rejection immune response as
      well. However, systemic treatment with CD154 has some potential risks. Therefore,
      searching for efficient and safe strategies of CD154-based cancer therapy has
      been a hot topic in human cancer research. This review focuses on the latest
      discovered functions of CD40-CD154 interaction in cell immune responses and on
      the new findings of CD154-based human cancer therapy.

PMID- 15153778
TI  - Lentiviral vectors.
AB  - Vectors based on lentiviruses have reached a state of development such that
      clinical studies using these agents as gene delivery vehicles have now begun.
      They have particular advantages for certain in vitro and in vivo applications
      especially the unique capability of integrating genetic material into the genome
      of non-dividing cells. Their rapid progress into clinical use reflects in part
      the huge body of knowledge which has accumulated about HIV in the last 20 years.
      Despite this, many aspects of viral assembly on which the success of these
      vectors depends are rather poorly understood. Sufficient is known however to be
      able to produce a safe and reproducible high titre vector preparation for
      effective transduction of growth-arrested tissues such as neural tissue, muscle
      and liver.

PMID- 15153779
TI  - Myofibril MgATPase activities and energy metabolism in cardiomyopathic mice with
      diastolic dysfunction.
AB  - To study the genomic physiology of cardiac myofibril proteins in the heart, we
      have successfully created a cardiac troponin I (cTnI; a myofibril protein) gene
      knockout mouse model using gene targeting techniques. The phenotype of the cTnI
      gene knockout mouse is a cardiomyopathy with diastolic dysfunction resulting in
      sudden death in neonates. In the present studies, energy metabolism was analyzed
      in myocardial cells from cTnI-null hearts. Myofibril MgATPase activities were
      determined in myocardial cells from either wild-type or cTnI mutant mouse hearts.
      Furthermore, the quantity and quality of the mitochondria in wild-type and cTnI
      mutant animals were counted and analyzed. Our results demonstrate that damaged
      relaxation and increased Ca(2+)-independent force production in cTnI-null hearts
      is in part related to the increased myofibril MgATPase activities accompanied by
      an increase in mitochondria quantity and mitochondrial ATPase activities. These
      data indicate that cardiomyopathies with diastolic dysfunction are different from
      cardiomyopathies caused by systolic dysfunction. The former involves the damage
      of cardiac relaxation due to increased MgATPase activities and increased Ca(2+)
      independent force production inside of myofilaments, while the latter involves
      the damage of systolic contraction due to decreased MgATPase activities and
      decreased force production.

PMID- 15153780
TI  - GABA-B receptor activation in the rat globus pallidus potently suppresses
      pentylenetetrazol-induced tonic seizures.
AB  - To determine the involvement of the globus pallidus in mediating epilepsy, the
      effects of microinjection of a GABA uptake blocker (tiagabine), a benzodiazepine
      agonist (zolpidem) and a GABA-B receptor agonist (baclofen) on pentylenetetrazol
      (PTZ)-induced tonic seizure were examined in adult rats. Administration of PTZ
      induced tonic seizures in all control animals, accompanied with a 100% mortality
      rate. Pretreatment with bilateral intrapallidal microinjection of tiagabine (1
      mM) suppressed the incidence of tonic seizures to 67.7% and reduced the mortality
      rate to 16.7%. Furthermore, the latency to tonic seizures was 1,275 +/- 277 s,
      which was significantly longer than that of the corresponding control animals
      (319 +/- 225 s). On the other hand, administration of zolpidem (1 mM) was without
      significant effects on the mortality rate, the incidence and latency of the tonic
      seizure. In sharp contrast, microinjection of baclofen (1 mM) completely
      suppressed PTZ-induced tonic seizures and reduced the mortality rate to 0%. This
      effect was largely abolished by co-injection of the GABA-B receptor antagonist
      CGP55845. To elucidate the direct cellular action of baclofen, the excitability
      and membrane potential of globus pallidus neurons were studied by cell-attached
      and whole-cell patch-clamp recordings in the brain slice. Bath application of
      baclofen (50 microM) significantly reduced the firing of these neurons, and was
      often accompanied by a clear membrane hyperpolarization, in a CGP55845-sensitive
      manner. These data suggest that activation of GABA-B receptors in globus pallidus
      could significantly modulate PTZ-induced tonic seizures.

PMID- 15153781
TI  - Ascorbyl palmitate augments hypoxic respiratory response in the cat.
AB  - The redox signaling is germane for the hypoxia-sensing mechanisms at the carotid
      body. This raises the strong possibility that agents possess reducing and
      antioxidant attributes, such as ascorbate, could influence the hypoxic
      respiratory response. However, water solubility of ascorbate makes its
      effectiveness at membrane-associated target sites dubious. In this study, we
      sought to determine the effect of ascorbyl-6-palmitate (AP), a lipid-soluble
      derivative of ascorbate which penetrates biomembranes, on hypoxic respiration in
      the anesthetized, paralyzed and ventilated cat. AP was given by gavage: 600 mg/kg
      daily for 6 days before the beginning of the acute experiment. Respiration was
      then assessed from the phrenic electroneurogram, from which peak phrenic
      amplitude, a surrogate of tidal component, respiratory frequency, and their
      product, the minute phrenic output, were quantified. The response to normocapnic
      hypoxia, 7% O(2) in N(2), in the AP-treated cats was compared with that in
      controls. We found that AP augmented hypoxic respiration, delayed the appearance
      of hypoxic depression and decreased it, although the stimulatory/depressant
      character was preserved. The results suggest that the ascorbate moiety of AP
      interacts with the hypoxia-sensing mechanisms. Ascorbate may affect hypoxic
      respiration at multiple stages of chemotransduction pathways, which are subject
      to continuing uncertainties. The study highlights the augmentative effect of AP,
      a redox modulator, on hypoxic respiration, which may have a therapeutic
      potential.

PMID- 15153782
TI  - Protective effect of nicotinamide on neuronal cells under oxygen and glucose
      deprivation and hypoxia/reoxygenation.
AB  - Nicotinamide (vitamin B(3)) reduces the infarct volume following focal cerebral
      ischemia in rats; however, its mechanism of action has not been reported. After
      cerebral ischemia and/or reperfusion, reactive oxygen species (ROS) and reactive
      nitrogen species may be generated by inflammatory cells through several cellular
      pathways, which can lead to intracellular calcium influx and cell damage.
      Therefore, we investigated the mechanisms of action of nicotinamide in
      neuroprotection under conditions of hypoxia/reoxygenation. Results showed that
      nicotinamide significantly protected rat primary cortical cells from hypoxia by
      reducing lactate dehydrogenase release with 1 h of oxygen-glucose deprivation
      (OGD) stress. ROS production and calcium influx in neuronal cells during OGD were
      dose-dependently diminished by up to 10 mM nicotinamide (p < 0.01). This effect
      was further examined with OGD/reoxygenation (H/R). Cells were stained with the
      fluorescent dye 4,6-diamidino-2-phenylindole (DAPI) or antibodies against anti
      microtubule-associated protein-2 and cleaved caspase-3. Apoptotic cells were
      studied using Western blotting of cytochrome c and cleaved caspase-3. Results
      showed that vitamin B(3) reduced cell injury, caspase-3 cleavage and nuclear
      condensation (DAPI staining) in neuronal cells under H/R. In addition,
      nicotinamide diminished c-fos and zif268 immediate-early gene expressions
      following OGD. Taken together, these results indicate that the neuroprotective
      effect of nicotinamide might occur through these mechanisms in this in vitro
      ischemia/reperfusion model.

PMID- 15153783
TI  - Acute tolerance to ethanol inhibition of NMDA-induced responses in rat rostral
      ventrolateral medulla neurons.
AB  - The present study was performed to examine the effects of acute ethanol exposure
      on N-methyl-D-aspartate (NMDA)-induced responses and the development of acute
      tolerance in rat rostral ventrolateral medulla (RVLM) in vivo and in vitro.
      Repeated microinjections of NMDA (0.14 nmol) into the RVLM every 30 min caused
      reproducible increases in mean arterial pressure in urethane-anesthetized rats
      weighing 325-350 g. Intravenous injections of ethanol (0.16 or 0.32 g, 1 ml)
      inhibited NMDA-induced pressor effects in a blood-concentration-dependent and
      reversible manner. The inhibitory effect of ethanol was reduced over time during
      continuous infusion of ethanol or on the second injection 3.5 h after prior
      injection of a higher dose of ethanol (0.32 g). A high dose of ethanol (0.32 g)
      had no significant effects on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid, gamma-aminobutyric acid and glycine-induced changes in blood pressure. In
      vitro studies showed that ethanol (10- 100 mM) dose-dependently inhibited inward
      currents elicited by pressure ejection of NMDA (10 mM) in RVLM neurons of
      neonatal brainstem slice preparations. When the superfusion time of ethanol (100
      mM) was increased to 50 min, its inhibitory effect decreased gradually after 30
      40 min in 60% of RVLM neurons examined. These data suggested that ethanol
      inhibition and subsequent tolerance development is associated with changed
      sensitivity to NMDA in the RVLM, which may play important roles in the ethanol
      regulation of cardiovascular function.

PMID- 15153784
TI  - A DNA vaccine co-expressing antigen and an anti-apoptotic molecule further
      enhances the antigen-specific CD8+ T-cell immune response.
AB  - We have shown that DNA encoding the anti-apoptotic protein Bcl-xL enhances E7
      specific CD8+ T-cell responses and DNA encoding pro-apoptotic protein caspase-3
      suppresses E7-specific CD8+ T-cell responses when co-administered intradermally
      via gene gun with DNA encoding human papillomavirus type 16 (HPV-16) E7 linked to
      the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1).
      E7 and LAMP-1 are linked to form the chimeric Sig/E7/LAMP-1 (SEL). Because co
      administration does not ensure delivery of both constructs to a single cell, we
      used pVITRO, a mammalian expression vector with double promoters, to ensure
      expression of both molecules in the same cell. We vaccinated C57BL/6 mice with
      pVITRO-SEL-Bcl-xL, pVITRO-SEL-mtBcl-xL, pVITRO-SEL, or pVITRO-SEL-caspase-3
      intradermally via gene gun and intramuscularly via injection. We demonstrated
      that vaccination with pVITRO achieved similar results to a co-administration
      strategy: that Bcl-xL enhanced the E7-specific CTL response and caspase-3
      suppressed the E7-specific CTL response. In addition, we found intradermal
      vaccination elicited significantly higher numbers of E7-specific CD8+ T cells
      compared to intramuscular vaccination. Thus, intradermal vaccination with a
      pVITRO vector combining an anti-apoptotic strategy (Bcl-xL) and an intracellular
      targeting strategy (SEL) further enhances the E7-specific CD8+ T-cell response
      and guarantees co-expression of both encoded molecules in transfected cells.

PMID- 15153786
TI  - Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in
      breast cancer patients.
AB  - Diagnosis and follow-up of bone metastases in breast cancer patients usually rely
      on symptoms and imaging studies. Tartrate-resistant acid phosphatase 5b (TRACP
      5b) is a specific marker of osteoclasts and is herein proposed as a marker of
      bone metastasis in breast cancer patients. An immunoassay using a monoclonal
      antibody, 14G6, was used to measure the activity of serum TRACP 5b at pH 6.1 in
      30 early breast cancer patients without bone metastasis and in 30 aged-matched
      breast cancer patients with bone metastasis. Another 60 normal volunteers were
      recruited as controls. Bone alkaline phosphatase (BAP), a traditional marker of
      bone turnover, was also measured in selected cases. The overall mean TRACP 5b
      activity in normal women was 2.83 +/- 1.1 U/l, and it increased with age. The
      mean TRACP 5b activity in early breast cancer patients did not differ from that
      of the normal group (2.93 +/- 0.64 vs. 2.83 +/- 1.1 U/l; p = 0.66), whereas it
      was significantly higher in breast cancer patients with bone metastasis (5.42 +/-
      2.5 vs. 2.83 +/- 1.1 U/l; p < 0.0001). BAP activity was significantly higher in
      breast cancer patients with bone metastasis than in early breast cancer patients
      (p = 0.004). Serum TRACP 5b activity correlated well with BAP activity in breast
      cancer patients with bone metastasis (p < 0.0001), but not in normal individuals
      or in patients without bone metastasis. TRACP 5b activity can be considered a
      surrogate indicator of bone metastasis in breast cancer patients.

PMID- 15153785
TI  - Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation
      of the extracellular signal-regulated kinase signaling pathway.
AB  - Infection of bovine arterial endothelial (BAE) cells with bovine herpesvirus-4
      (BHV-4) induced biphasic activation of one of the cellular mitogen-activated
      protein kinase (MAPK) downstream targets, extracellular signal-regulated kinase
      (ERK). ERK activity reached a maximum within 0.5 h postinfection (h.p.i.), and
      had declined and returned to basal levels by 2 h.p.i. However, at 18- 24 h.p.i.,
      a second phase of increased ERK activation occurred. Treatment of BHV-4-infected
      BAE cells with either U0126, a potent inhibitor of MAPK/ERK kinase, or arsenite
      dose-dependently blocked ERK activation and inhibited viral DNA synthesis and
      viral replication in the culture. Further detailed investigations revealed that
      transcription of viral immediate-early gene 2 (IE-2), which is required for viral
      DNA replication, was significantly suppressed by both U0126 and arsenite. These
      results imply that ERK activation may play a pivotal role in herpesvirus
      replication, and that inhibition of ERK activation can effectively inhibit viral
      IE protein synthesis and viral replication.

PMID- 15153787
TI  - Interleukin-6 increases vascular endothelial growth factor and angiogenesis in
      gastric carcinoma.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine associated with the disease
      status of gastric carcinoma (GC). Vascular endothelial growth factor (VEGF) is a
      potent tumor angiogenic factor in GC. In this study, we attempted to clarify
      whether IL-6 can regulate VEGF and angiogenesis in GC. GC samples from 54
      surgical specimens were subjected to immunohistochemical examination of IL-6,
      VEGF, and tumor microvessels, and results showed that IL-6 was positively
      correlated with VEGF expression and tumor vasculature. We determined VEGF
      expression in four GC cell lines by ELISA, revealing that GC cells can produce
      significant amount of VEGF with increasing dose and duration of IL-6 stimulation.
      Next, a luciferase reporter gene assay was employed to determine the signaling
      pathway driving the VEGF promoter by IL-6, which showed that the JAK/STAT pathway
      is involved in the stimulation of VEGF gene expression. The effects of IL-6 on
      angiogenesis in vitro and in vivo were evaluated by HUVEC studies and the
      Matrigel plug assay, respectively. Results showed that IL-6 effectively promoted
      HUVEC proliferation and tube formation in vitro and Matrigel plug vascularization
      in vivo, primarily by inducing VEGF in GC. This study provides evidence that the
      multifunctional cytokine, IL-6, may induce VEGF expression which increases
      angiogenesis in gastric carcinogenesis.

PMID- 15153788
TI  - Decreased expression of the pancreatic secretory trypsin inhibitor II gene during
      aging of the rat liver.
AB  - The genetic constitution and differential gene expression of an organism play
      important roles in controlling the species-specific rate of aging and the maximum
      life span potential. We utilized a differential-display polymerase chain reaction
      technique to identify the age-dependent expression of genes in the rat liver. We
      demonstrate in this report, for the first time, that expression of the pancreatic
      secretory trypsin inhibitor II (PSTI-II) gene declines drastically during aging.
      We confirmed this decrease by Northern blot analysis. Low PSTI-II levels in aged
      animals might result in a lack of protection from prematurely activated trypsin
      like proteases, which would thus enhance inflammation.

PMID- 15153789
TI  - Gelatinolytic and fibrinolytic activity in fresh-frozen plasma.
AB  - Fresh-frozen plasma (FFP) was evaluated for gelatinolytic and fibrinolytic
      activity. Gelatin zymography revealed that gelatinase A (MMP-2) was
      constitutively present in FFP whereas gelatinase B (MMP-9) was present at
      variable levels. The presence of MMP-9 likely represents differential release
      from neutrophils during FFP collection or processing. Although fibrin matrices
      generated from FFP or freshly prepared plasma contained characteristic
      crosslinked gamma-gamma dimers and beta-monomers, matrices generated from FFP
      were resistant to spontaneous plasmin-dependent fibrinolysis. This observation
      likely stems from the plasminogen activator instability and could potentially
      lead to a hypofibrinolytic state. The impact of these in vitro findings to
      protease balance in patients receiving multiple FFP doses remains to be
      determined.

PMID- 15153790
TI  - Decreased total nitric oxide production in patients with duchenne muscular
      dystrophy.
AB  - Plasma nitric oxide (NO) levels in Duchenne muscular dystrophy (DMD) patients
      were significantly lower than those observed in both healthy controls and in
      patients with other neuromuscular disorders. The correlation between NO level and
      ejection fraction was significant (r = -0.384, p = 0.0391) in the DMD group.
      Disruption of NO systems may contribute to the development of muscular dystrophy
      and have implications for therapeutic strategies.

PMID- 15153791
TI  - TH1/TH2 paradigm in pregnancy: paradigm lost? Cytokines in pregnancy/early
      abortion: reexamining the TH1/TH2 paradigm.
AB  - In this paper, we briefly survey the history of concepts in reproductive
      immunology from antibody-mediated tolerance to the "fetal allograft" to the
      current concept of an embryo "bathing in a sea of cytokines". We then review the
      paradigm that "allopregnancy is a Th2 phenomenon" and some of the evidence gained
      in animals and humans supporting it. We continue by discussing the light it sheds
      on immunologically caused recurrent abortion, and the present status of the
      concepts. We next show the limits of the Th1/Th2 paradigm by reviewing the role
      of "inflammatory" cytokines in implantation (as first seen with leukemia
      inhibitory factor). We go on to discuss recent data showing that interferon-gamma
      is not solely a "bad guy", e.g. abortifacient as the paradigm would predict, but
      is needed at low doses for the vascular development and transformation of uterine
      spiral arteries required for implantation and successful pregnancy. We conclude
      by discussing the emerging role of NK and IL-12, IL-15, IL-18 tripods and other
      cytokines in local angiogenesis and tissue remodelling, a series of new data
      bringing us well beyond the Th1/Th2 paradigm in pregnancy which, in this context,
      appears now obsolete and an oversimplification, although it has indeed been
      useful at first. Rather, step-specific events have to be considered and a key
      role is seen in local tissue remodelling, in which immune cytokines play an
      important role while not always being secreted by immune cells.

PMID- 15153792
TI  - Molecular determinants controlling homeostatic recirculation and tissue-specific
      trafficking of lymphocytes.
AB  - The homeostasis of the immune system is maintained by the recirculation of naive
      lymphocytes through the secondary lymphoid tissues, such as the lymph nodes,
      Peyer's patches, and spleen. Upon insult by pathogens or antigens, lymphocytes
      become activated, and the regulated trafficking of these cells results in the
      integration of systemic and regional immune responses. The exquisite specificity
      of such lymphocyte trafficking is determined by tissue-specific guidance signals
      expressed by the endothelial cells of postcapillary venules, combined with
      counterreceptors expressed by the circulating lymphocytes. The high endothelial
      venules can selectively guide naive lymphocytes into the lymph nodes and Peyer's
      patches by expressing a unique combination of vascular addressins, lymphocyte
      specific chemokines, and chemokine-binding molecules. The inflamed postcapillary
      venules in extralymphoid tissues, such as the skin and intestinal lamina propria,
      also use a distinct array of endothelial adhesion molecules and tissue- selective
      chemokines, and support the recruitment of effector and memory lymphocytes that
      express the appropriate receptors for tissue-specific trafficking. In this
      review, we summarize the present understanding of the homeostatic recirculation
      of naive lymphocytes through the secondary lymphoid tissues and the specific
      targeting of antigen-experienced lymphocytes into the effector sites. We also
      revisit some previous studies that reported apparently conflicting observations.

PMID- 15153793
TI  - Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4
      and interleukin-13 production by activated human basophils.
AB  - BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and
      IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This
      time, we investigated the inhibition of IL-4 and IL-13 production by basophils by
      other flavonoids and attempted to determine the fundamental structure of
      flavonoids related to inhibition. We additionally investigated whether flavonoids
      suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in
      response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were
      stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3
      in the presence of various concentrations of 18 different kinds of flavones and
      flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured.
      Leukotriene C4 synthesis was also measured after basophils were stimulated for 1
      h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids
      on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured
      with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin,
      fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and
      IL-13 production by basophils but did not affect leukotriene C4 synthesis. At
      higher concentrations, these flavonoids suppressed IL-4 production by T cells.
      Based on a hierarchy of inhibitory activity, the basic structure for IL-4
      inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory
      activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the
      intake of flavonoids, depending on the quantity and quality, may ameliorate
      allergic symptoms or prevent the onset of allergic diseases.

PMID- 15153794
TI  - German cockroach extract induces activation of human eosinophils to release
      cytotoxic inflammatory mediators.
AB  - BACKGROUND: Eosinophils play an important role in the pathogenesis of allergic
      diseases. Sensitization and exposure to cockroach allergen have been demonstrated
      to be one of the major risk factors for the development of bronchial asthma.
      However, little is known regarding the functional capacity of cockroach extract
      antigen to activate human eosinophils. OBJECTIVE: We investigated whether German
      cockroach extract can activate human eosinophils to release cytotoxic
      inflammatory mediators. METHODS: Purified eosinophils from the peripheral blood
      were incubated with various concentrations (0-200 microg/ml) of German cockroach
      extract antigen. Effector functions of eosinophils were checked by degranulation
      and superoxide anion production. In addition, we examined surface expression of
      CD11b and CD69, and intracellular activation of p38 mitogen-activated protein
      kinase (p38 MAP kinase) in cockroach-stimulated eosinophils. RESULTS: German
      cockroach extract induced degranulation and superoxide production from human
      eosinophils. In addition, incubation of eosinophils for 3 h with the cockroach
      extract resulted in an increased level of the surface expression of CD11b and
      CD69. Furthermore, cockroach-induced superoxide production from eosinophils was
      significantly inhibited by the pretreatment of cells with a p38 MAP kinase
      inhibitor SB202190. Indeed, a large amount of phosphorylated forms of p38 MAP
      kinase was detected in cockroach-stimulated eosinophils. CONCLUSIONS: Our results
      suggest that German cockroach extract induces activation of human eosinophils to
      release cytotoxic inflammatory mediators such as superoxide and granular
      proteins.

PMID- 15153795
TI  - ADRB2 polymorphisms and asthma susceptibility: transmission disequilibrium test
      and meta-analysis.
AB  - BACKGROUND: The beta(2)-adrenergic receptor (ADRB2) is the most common adrenergic
      receptor in the lung, and associations between ADRB2 polymorphisms and
      intermediate phenotypes of asthma have been reported. Four missense polymorphisms
      (Arg16Gly, Gln27Glu, Val34Met, and Thr164Ile) and one polymorphism in the 5'
      leader cistron of the ADRB2 messenger RNA has been identified. In vitro studies
      have shown that these missense polymorphisms can affect ADRB2 function. METHODS:
      To examine possible associations of ADRB2 polymorphisms with asthma
      susceptibility, we performed transmission disequilibrium tests (TDT) of 137
      Japanese families identified through children with atopic asthma. RESULTS: We did
      not find associations between any alleles of the ADRB2 polymorphisms and asthma
      by TDT (p > 0.1). We also performed a meta-analysis of data from all available
      studies. The random-effects model showed no significant odds ratio for the
      Arg16Gln (odds ratio = 1.05, p = 0.53) or Gln27Glu (odds ratio = 1.12, p = 0.22)
      polymorphism. CONCLUSION: Our data indicate that ADRB2 does not contribute
      substantially to susceptibility to asthma, but it is possible that these
      polymorphisms influence disease activity and drug responses in individuals with
      asthma.

PMID- 15153796
TI  - Epidemic asthma in Barcelona: an evaluation of new strategies for the control of
      soybean dust emission.
AB  - BACKGROUND: Asthma attacks and mortality due to inhalation of soybean antigens in
      Barcelona have been well documented. Strict protective measures in the unloading
      process were established in 1998 to avoid the release of soybean dust into the
      atmosphere. The present study was undertaken to assess the effectiveness of these
      latest environmental measures, and, if effective, to recommend their
      implementation in the many harbours where soybean is unloaded. METHODS: Levels of
      soybean aeroallergen were analysed daily during a period of 5 years and 2 months
      in a total of 1,854 samples, 125 from the pre-intervention period and 1,729 from
      the postintervention period. Additionally, the number of asthma admissions to the
      emergency rooms of the city's three largest hospitals was recorded. Asthma
      patients attended at home by the public home emergency service and judicial
      autopsies registering asthma deaths were also investigated. RESULTS: The mean
      concentration of soybean aeroallergen was 159 U/m(3) in the pre-intervention
      period and 39 U/m(3) in the postintervention period (p < 0.0001). Significant
      differences in postintervention aeroallergen concentrations were found between
      days of soybean unloading (42 U/m(3)) and days of no unloading (33 U/m(3)), with
      p < 0.0001. No significant relationship was found between concentrations of
      environmental soybean aeroallergens and the number of emergency room admissions
      for asthma. CONCLUSIONS: Implementation of stricter protective measures in silos
      for the soybean unloading process has reduced the concentration of soybean dust
      in the atmosphere and evidences the effectiveness of the measures adopted.

PMID- 15153797
TI  - Role and modulation of CD16 expression on eosinophils by cytokines and immune
      complexes.
AB  - BACKGROUND: Blood eosinophils express CD16 on their surface when stimulated in
      vitro with platelet-activating factor or IFNgamma. Transient expression of CD16
      is also observed in vivo following aeroallergen challenge of asthmatic subjects.
      The present work is aimed at evaluating the possible mechanisms modulating
      eosinophil expression of CD16 and the biological functions of this receptor.
      METHODS: First, purified blood eosinophils were incubated with IL-1beta, IL-2, IL
      4, IL-5, IL-9 or IL-16, GM-CSF, IFNgamma, eotaxin or 5-oxo-ETE and CD16
      expression was measured. Second, the capacity of CD16 to mediate degranulation
      induced by IgG immune complexes (IC) was evaluated in eosinophils with low and
      high CD16 expression. Finally, serum allergen-specific IgE and IgG, and total IgE
      levels were measured at baseline in allergic asthmatics and correlated with
      changes observed in blood eosinophil CD16 expression (DeltaCD16) following
      allergen challenge. RESULTS: Only IFNgamma and IL-2 significantly increased the
      number of CD16+ eosinophils, respectively, 37 +/- 10% (p = 0.0038) and 38 +/- 8%
      (p = 0.0006), compared to control, 7 +/- 2%. IgG IC induced degranulation in
      eosinophils with low and high CD16 expression and monoclonal anti-CD16 and anti
      CD32 antibodies inhibited this. IgG IC increased eosinophil CD16 expression (14
      +/- 6%, p = 0.0008) and this effect was blocked by pretreatment with anti-CD32
      antibodies. DeltaCD16 following allergen challenge correlated with the specific
      IgG/total IgE ratio (r(2) = 0.41, p = 0.036). CONCLUSION: These data suggest that
      formation of IgG IC is associated with surface eosinophil CD16 expression in
      asthma and that CD16 in cooperation with CD32 mediates IC-induced degranulation.

PMID- 15153798
TI  - Qualitative and quantitative evaluation of bird-specific IgG antibodies.
AB  - BACKGROUND: Exposure to organic dust produced by birds often gives rise to an
      immune response, e.g. IgG antibodies, but intense exposure can lead to high
      concentrations of IgG antibodies and the development of allergic alveolitis,
      often known as "bird fancier's lung". The aim of this study was to establish the
      distribution of bird-specific IgG antibodies in exposed and nonexposed
      individuals and compare a nonquantitative and quantitative method in evaluating
      raised levels of IgG antibodies. METHODS: Sera were collected in Sweden and South
      Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot
      antigens were quantified using the UniCAP system. Results were compared to the
      precipitation in gel assay. The IgG antibody values of symptomatic patients
      without precipitating antibodies (non-PP group; n = 51) and patients with
      precipitating antibodies (PP group; n = 34) were analyzed and compared to
      nonexposed asymptomatic blood donors (BD group; n = 73) and environmentally
      exposed pigeon breeders (n = 11). RESULTS: The IgG antibody response of the
      analyzed groups in Sweden and South Africa did not vary significantly from each
      other. IgG antibody responses were the strongest to pigeon antigens with clear
      increased IgG antibody levels in the PP group [geometric mean (GM) 603 mg/l]
      compared to the non-PP (GM 6.9 mg/l) and BD group (GM 5.0 mg/l). Threshold
      values, calculated as the GM value from the BD group plus 3 standard deviations
      (99% confidence interval), were 9.8, 10.8 and 10.0 mg/l for pigeons, budgerigars
      and parrots, respectively. Comparison of the two methods resulted in a good
      concordance with a level of agreement of 94.1% (kappa statistic = 0.83).
      CONCLUSIONS: The UniCAP system for the detection of bird-specific IgG antibodies
      is a highly reproducible, generally available, quantitative method for routine
      diagnostic testing and monitoring of exposed subjects with a very high level of
      agreement to the precipitating gel assay.

PMID- 15153799
TI  - Mixed medullary-follicular thyroid carcinoma. Report of a case and review of the
      literature.
AB  - OBJECTIVE: The aim was to describe the case of a female patient with a mixed
      medullary-follicular thyroid carcinoma. METHODS: The patient underwent
      thyroidectomy for the treatment of multinodular goiter. A tumor was found which
      exhibited the features of a mixed medullary-follicular thyroid carcinoma.
      Immunohistochemistry was performed. RESULTS: Immunohistochemistry was positive in
      the area of the carcinoma for calcitonin and thyroglobulin. She developed
      extensive metastatic deposits in the bones of the pelvis and in the calvarium
      causing hyperthyroidism. CONCLUSION: A patient with a mixed medullary-follicular
      thyroid carcinoma is described, who had elevated levels of both calcitonin and
      thyroglobulin and developed metastatic deposits, which could produce thyroid
      hormones.

PMID- 15153800
TI  - Geminin coordinates cell cycle and developmental control.
AB  - Growth and differentiation are two major themes in embryonic development.
      Numerous cell divisions have to be regulated on the path from a unicellular
      embryo, the zygote, to the multicellular structures of a mature being. Numerous
      functions, specializations and cellular identities have to be generated, in order
      to form a complex and mature animal. Numerous mechanisms have to control the
      correct assignment and acquisition of cellular fates, as well as the right timing
      and allocation of cells. Therefore, a strict coordination has to occur between
      embryonic patterning and the cell cycle. From this point of view, dual roles or
      mutual interactions of typical proliferation and developmental control genes are
      likely. Recently, new light was shed on these issues by identifying the nuclear
      protein Geminin as a molecular coordinator between the cell cycle and axial
      patterning. We summarize the role of Geminin in cell cycle, in the embryonic
      patterning controlled by Hox genes, providing insights into cell cycle regulators
      in embryonic development, and conversely, typical developmental control genes in
      cell cycle regulation.

PMID- 15153801
TI  - Histone-deacetylase inhibitors for the treatment of cancer.
AB  - Histone deacetylase inhibitors (HDACi) are a promising new class of
      chemotherapeutic drug currently in early phase clinical trials. A large number of
      structurally diverse HDACi have been purified or synthesised that mostly inhibit
      the activity of all eleven class I and II HDACs. While these agents demonstrate
      many features required for anti-cancer activity such as low toxicity against
      normal cells and an ability to inhibit tumor cell growth and survival at
      nanomolar concentrations, their mechanisms of action are largely unknown.
      Initially, a model was proposed whereby HDACi-mediated transactivation of a
      specific gene or set of genes was responsible for the inhibition of cell cycle
      progression or induction of apoptosis. Given that HDACs can regulate the activity
      of a number of nonhistone proteins and that histone acetylation is important for
      events such as DNA replication and mitosis that do not directly involve gene
      transcription, it appears that the initial mechanistic model for HDACi may have
      been too simple. Herein, we provide an update on the transcription-dependent and 
      independent events that may be important for the anti-tumor activities of HDACi
      and discuss the use of these compounds in combination with other chemotherapeutic
      drugs.

PMID- 15153802
TI  - Targeting prostate-specific membrane antigen in cancer therapy: can molecular
      medicine be brought to the surface?
AB  - Systemic chemotherapy can be associated with significant morbidity as a result of
      non-specific side effects and drug toxicity. A major advance in cancer therapy is
      the ability to target specific molecules and pathways due to increased knowledge
      of gene expression and biochemical function. In this issue of Cancer Biology &
      Therapy, a targeted approach to prostate cancer chemotherapy is explored using
      the inherent enzymatic activity of prostate-specific membrane antigen (PSMA) and
      peptide conjugated methotrexate. Substrate specificity and specific activity were
      determined using soluble PSMA while selective drug toxicity was determined using
      clonal inhibition of PSMA+ and PSMA- cancer cell lines. Peptide conjugates linked
      to methotrexate were identified with enhanced selective clonal inhibition in the
      presence of PSMA. Despite these promising results, multiple variables affecting
      clinical feasibility such as substrate stability and non-PSMA dependent drug
      uptake will require careful consideration before PSMA is ready for prime time as
      a selective chemotherapeutic target.

PMID- 15153804
TI  - Towards a long-lasting immune prevention of HER2 mammary carcinomas: directions
      from transgenic mice.
AB  - Several theoretical and practical issues differentiate immune prevention from
      tumor immune therapy. The latter seeks to induce a rapid reaction against a life
      threatening tumor, whereas prevention is dictated by the need to maintain
      constant surveillance of a situation in which an event is foreseen, but may not
      occur. The time frame of successful prevention is therefore long and often
      lifelong. Time itself is thus a key factor in the elaboration of vaccines to
      prevent tumor growth and its great length in preventive management poses new
      immunological problems that cannot be studied in short-term vaccination-challenge
      experiments. Many recent data indicate that HER2 receptor displays several
      features of an ideal tumor associated antigen and that an immune response can
      significantly alter HER2 tumor progression. We are thus using vaccination in the
      immune prevention and cure of carcinomas in HER2 transgenic mice in the search
      for a rationale for the application of preventive and curative vaccination for
      patients with HER2/ErbB-2 neoplastic lesions or at risk of recurrence after
      successful surgery. The design of effective immunopreventive approaches that can
      be translated to human situations is an important issue. A molecularly defined,
      effective and validated anti HER2 vaccine and the definition of immune mechanisms
      leading to the inhibition of HER2-driven neoplastic proliferation may provide a
      new way of treating these patients.

PMID- 15153803
TI  - Identification of a transcriptional profile associated with in vitro invasion in
      non-small cell lung cancer cell lines.
AB  - Although much has been learned about basic mechanisms of cell invasion, the genes
      whose expression is required for this process by malignant cell lines have
      remained obscure. We assessed invasion through Matrigel using EGF as a
      chemoattractant and gene expression profiles using oligonucleotide microarrays
      for 22 non-small cell lung cancer cell lines. The expression of 22 genes were
      significantly correlated (p < 0.001) with the measured invasion index. Cluster
      analysis demonstrated that gene expression profiles classify the cell lines into
      low and high invasive subgroups. Considering invasiveness as a dichotomous
      variable, Bayesian analysis was used to identify genes that have the highest
      probability of being differentially expressed between the high and low invasion
      groups. This analysis identified 16 genes whose expression was associated with
      invasiveness. "Leave one out" cross validation was 91% accurate. Nine genes were
      identified in both correlation and Bayesian analyses. Seven of the nine genes
      were negatively associated with invasion and four of those genes are plasma
      membrane proteins. The two genes with the highest inverse association with
      invasion, TACSTD1 and CLDN3, are involved with cell adhesion and cell-cell
      interactions, respectively. Interestingly, the gene with the highest positive
      association with invasion, SERPINE1 (PAI-1), is a protease inhibitor. These and
      the other genes identified by both analyses represent targets for further study
      to assess their importance in non-small cell lung cancer invasion and metastasis.

PMID- 15153805
TI  - The normal response to RAS: senescence or transformation?
AB  - Normal cells are thought to protect against transformation by undergoing a
      permanent cell cycle arrest, cellular senescence, in response to the expression
      of activated oncogenes such as RAS. We recently found that freshly established
      neonatal human fibroblasts are resistant to RAS-induced senescence. Moreover,
      extended passaging of normal fibroblasts leads to increased levels of the cyclin
      dependent kinase inhibitor p16 and sensitizes cells to senescence induced by RAS.
      These findings implicate exogenous stress as a necessary cofactor in RAS-induced
      senescence and demonstrate that RAS expression can promote some characteristics
      of transformation in the absence of other genetic changes.

PMID- 15153806
TI  - Tumor angiogenesis in mice and men.
AB  - Over the past decade much research has focused on understanding the molecular
      pathways that regulate the development of a tumor-associated vasculature. In
      1999, Lyden and colleagues showed that mice deficient in one to three Id1 or Id3
      alleles could not support the growth of tumor xenografts due to defects in tumor
      associated angiogenesis. Three recently published manuscripts have now re
      examined the role of Id genes in the development of a tumor-associated
      vasculature using more clinically relevant tumor model systems. Remarkably, all
      three studies have found strikingly different results compared to the original
      xenograft data published in 1999. Below we review the current understanding of
      the role of Id genes in the development of a tumor-associated vasculature given
      the most recent data and suggest ways in which animal tumor model systems might
      be put to better use to provide more clinically relevant information.

PMID- 15153807
TI  - Coordination of DNA synthesis and histone gene expression during normal cell
      cycle progression and after DNA damage.
AB  - Chromosomal DNA replication and histone synthesis are tightly coupled during S
      phase of the eukaryotic cell division cycle. Recently we reported that mRNA
      levels of mammalian replication-dependent histones, both linker histone H1 and
      four core histones (H2A, H2B, H3 and H4), are coordinately downregulated in
      parallel with the inhibition of DNA synthesis upon DNA damage. Moreover, we
      showed that ionizing radiation induces inhibition of histone gene transcription
      through the G(1) checkpoint pathway. These results demonstrate that histone
      synthesis is coordinated with DNA synthesis not only under normal growth
      conditions but also under conditions where DNA damage may occur. Regulation of
      the cyclin E-Cdk2 substrate NPAT, which is essential for both histone gene
      expression and S phase entry, provides a mechanism coordinating histone and DNA
      synthesis in mammalian cells.

PMID- 15153809
TI  - Cancer biology--lost in translation?

PMID- 15153810
TI  - Hard-wired genotype in metastatic breast cancer.
AB  - Recently, we showed by gene-expression profiling that the molecular program
      established in a human primary breast carcinoma is highly preserved in its
      distant metastases. According to the predominant model of metastasis, the
      capacity of a primary tumor to metastasize is acquired only rarely and late in
      tumorigenesis. Our findings challenge this common theory and imply that the
      metastatic nature of 'poor prognosis profile' breast carcinomas is an inherent
      feature, and not reserved to advantageous subpopulations.

PMID- 15153808
TI  - Regulation of mammalian cell growth and death by bacterial redox proteins:
      relevance to ecology and cancer therapy.
AB  - Recent evidence indicates that bacterial redox proteins such as cupredoxins and
      cytochromes, that are normally involved in electron transfer during respiration,
      can enter mammalian cells and induce either apoptosis or inhibition of cell cycle
      progression. Such proteins have also been shown to demonstrate a good deal of
      specificity for entry and induction of cytotoxic effects in cancer cells,
      allowing both in vitro cell death and in vivo inhibition of cancer progression.
      An alteration in the hydrophobicity of the bacterial redox proteins can lead to a
      switch from apoptosis to growth arrest and vice versa through modulation of the
      intracellular levels of tumor suppressors. The preferential entry and
      cytotoxicity of these redox proteins in cancer cells raises interesting questions
      about the presence of other bacterial proteins that may affect cell cycle at the
      G(2)/M phase, thereby potentially arresting cancer growth. The intracellular
      localization of the bacterial redox proteins in nonpathogenic soil bacteria
      similarly raises questions about their possible role in allowing various
      nonpathogenic soil bacteria to defend themselves from environmental predators by
      inducing cytotoxicity when engulfed in large numbers. A new role of the redox
      proteins in soil bacteria in maintaining an ecological balance among the
      predators and preys is proposed.

PMID- 15153811
TI  - Pictures, progress, and perplexities: the immediate cell biological effects of
      ionizing radiation.
AB  - An unexpected image made by an invisible beam precipitated the discovery of X
      rays in the waning days of the 19th century. The usefulness and dangers of this
      new discovery soon became clear, emphasizing the importance of DNA damage
      recognition and repair after exposure to ionizing radiation (IR). One hundred
      years later, new images of the immediate effects of ionizing radiation have once
      again ignited excitement among investigators. The combination of advanced imaging
      techniques with new reagents targeting molecular components of the cellular DNA
      damage response have enabled visualization of sites of DNA damage, resulting in
      fresh insights into the immediate cell biological effects of IR. This review will
      review these advances, highlighting recent progress as well as critical questions
      that remain unanswered.

PMID- 15153812
TI  - A Kin I-dependent Pacman-flux mechanism for anaphase A.
AB  - Anaphase A chromatid-to-pole motion is fundamental for proper chromosome
      segregation in most systems. During the past several decades, two models for the
      mechanism of anaphase A have come to prominence. The Pacman model posits that
      chromatids induce the depolymerization of microtubule plus-ends embedded in
      kinetochores, thereby 'chewing' their way poleward. Alternatively, the Poleward
      flux model posits that chromatids are 'reeled-in' to poles by the continual
      depolymerization of the minus-ends of kinetochore-associated microtubules, which
      are focused at spindle poles. In a recent study, we reported that anaphase A in
      Drosophila requires the depolymerization of both ends of kinetochore-associated
      microtubules, simultaneously. This is driven by two members of the Kin I
      subfamily of kinesins, termed KLP59C and KLP10A, which target specifically to
      chromatids and spindle poles, respectively. We have termed this hybrid of Pacman
      and Poleward flux the Kin I-dependent Pacman-flux mechanism for anaphase A. Here,
      we discuss the implications of these findings and explore potential additional
      components required to drive chromatid-to-pole motion by such a mechanism.

PMID- 15153813
TI  - hTert-immortalized endothelial cells: an important new research tool.

PMID- 15153814
TI  - Estrogen receptor status, cell cycling and paclitaxel: looking for a "hormone"
      ious explanation.

PMID- 15153815
TI  - A clinical approach to the management of a patient with suspected renovascular
      disease who presents with leg ischemia.
AB  - Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive
      renal failure, and recurrent pulmonary edema. It typically occurs in high risk
      patients with coexistent vascular disease elsewhere. Most patients with ARAS are
      likely to die from coronary heart disease or stroke before end-stage renal
      failure occurs. Recent controlled trials have shown that most patients undergoing
      angioplasty to treat renovascular hypertension still need antihypertensive agents
      6 or 12 months after the procedure. Nevertheless, the number of antihypertensive
      agents required to control blood pressure adequately is lower following
      angioplasty than for medication alone. Trials assessing the value of
      revascularization for preserving renal function or preventing clinical events are
      only in the early recruitment phase. Revascularization should be undertaken in
      patients with ARAS and resistant hypertension or heart failure, and probably in
      those with rapidly deteriorating renal function or with an increase in plasma
      creatinine levels during angiotensin-converting enzyme inhibition. With or
      without revascularization, medical therapy using antihypertensive, hypolipidemic
      and antiplatelet agents is necessary in almost all cases.

PMID- 15153816
TI  - The prevalence of asymptomatic arterial obstruction in the lower extremities
      among men and women 60 to 69 years of age.
AB  - AIM: To estimate the prevalence of asymptomatic arterial obstruction in the lower
      extremities in men and women 60 to 69 years of age. METHODS: A sample of 333
      participants between 60 to 69 years of age attended a physical examination as
      part of a population based health study in Nord-Trondelag County, Norway (the
      HUNT Study). The total prevalence of arterial obstruction was defined as the
      proportion of subjects with ankle brachial pressure index lower than 0.9
      (ABPI<0.9). Further, the proportion of participants with arterial obstruction who
      also reported symptoms of intermittent claudication was defined as having
      symptomatic arterial obstruction. Finally, the prevalence of asymptomatic
      arterial obstruction was calculated as the difference between the total
      prevalence of arterial obstruction and the prevalence of symptomatic arterial
      obstruction. RESULTS: The total prevalence of arterial obstruction as defined by
      ABPI<0.9 was 7.8%. The prevalence was slightly higher among men (9.2%) than among
      women (6.9%), but the difference was not statistically significant (p-value=0.5).
      The prevalence of asymptomatic arterial obstruction was 6.3%, indicating that
      asymptomatic disease was approximately 4 times as frequent as symptomatic
      arterial obstruction (1.5%). The prevalence of asymptomatic arterial obstruction
      was nearly identical for men (6.2%) and women (6.4%). CONCLUSION: The total
      prevalence of arterial obstruction as defined by an ABPI<0.9 was 7.8% in this age
      group, and the prevalence of asymptomatic disease was 6.3%. Thus, only 1 in 5
      persons who had objectively measured arterial obstruction indicated symptoms of
      intermittent claudication.

PMID- 15153817
TI  - Autologous transplantation of peripheral blood endothelial progenitor cells
      (CD34+) for therapeutic angiogenesis in patients with critical limb ischemia.
AB  - AIM: Intramuscular injection of endothelial progenitor cells (EPCs) may
      constitute an alternative treatment strategy for patients with critical limb
      ischemia (CLI). We performed transplantations of EPCs (CD34(+)) extracted from
      peripheral blood in patients with CLI. The objective of this report is to present
      the method and early results of intramuscular autologous peripheral blood CD34(+)
      cell transplantation in the ischemic limb. METHODS: CD34(+) cell transplantation
      was performed in 2 limbs of 2 patients with CLI, in cases in which it was not
      possible to perform surgical or percutaneous revascularization. The patients
      received a granulocyte colony-stimulating factor (G-CSF) prior to the treatment.
      CD34(+) cells were retrieved from peripheral blood and injected directly into the
      muscle of the ischemic limb. RESULTS: CD34(+) cells retrieved in patient 1 were 1
      x 10(5)/ml and in patient 2 were 1.6 x 10(5)/ml. Transcutaneous oxygen pressure
      in the foot increased and clinical symptoms improved. Newly visible collateral
      blood vessels were directly documented by angiography. CONCLUSION: Satisfactory
      clinical improvement was achieved by using peripheral blood EPCs (CD34(+)) in the
      patients with CLI. No complications arose following the intramuscular
      administration of peripheral blood CD34(+) cells.

PMID- 15153818
TI  - Therapeutic angiogenesis for patients with limb ischemia by utilization of fibrin
      meshwork. Pilot randomized controlled study.
AB  - AIM: The aim of this paper is to assess the feasibility and efficacy of fibrin in
      inducing neovascularization as an angiogenic substance and/or carrier for
      vascular endothelial growth factor (VEGF) in patients with limb ischemia.
      METHODS: Twenty-three patients with limb ischemia and referred for below the knee
      amputations were randomized for treatment: group 1, 7 patients received only a
      saline injection; group 2, 9 received intramuscular injection of fibrin and group
      3, 7 received the fibrin composition with deferoxamine and added VEGF(165). The
      fibrin meshwork was introduced into the popliteal area of the diseased limbs
      using a dual syringe system (1 contained thrombin solution [1 mg, 5000 U] and 1
      contained fibrinogen [1 mg, Baxter Hyland Immuno] solution). In group 3,
      Deferoxamine (100 microg) and 500 microg of VEGF(165) were added to the
      fibrinogen solution. RESULTS: In the control group 5 patients had undergone below
      the knee amputation at the 3-6 month follow-up. Only 1 patient from Group 2 had
      below the knee amputation 5 months following Fibrin only administration. Clinical
      improvement was noted in all 8 patients following fibrin administration and in
      all 7 patients injected with the fibrin meshwork, deferoxamine and VEGF
      combination. CONCLUSION: IM injection of fibrin is safe and appears to be an
      efficient method to treat limb ischemia. These findings indicate that use of
      fibrin may be a novel and simple method for inducing therapeutic angiogenesis.

PMID- 15153819
TI  - The best TcpO(2) parameters to predict the efficacy of spinal cord stimulation to
      improve limb salvage in patients with inoperable critical leg ischemia.
AB  - AIM: Spinal cord stimulation (SCS) is available as an alternative therapy for
      patients suffering from inoperable critical limb ischemia (CLI). Selection of
      patients is essential to achieve the best treatment effect. For this purpose
      transcutaneous oxygen (TcpO(2)) measurements have frequently been applied. So
      far, it is unclear which TcpO(2) parameters serve this purpose best. METHODS:
      Studies in which inoperable CLI patients were treated with conservative treatment
      with or without SCS, and in whom various TcpO(2) measurements were performed
      before and during treatment were pooled to investigate which TcpO(2) parameter(s)
      were best to detect patients who benefit most from SCS treatment as to limb
      salvage. RESULTS: TcpO(2) in the supine position increased significantly
      (p<0.001) in patients after a short period of SCS treatment (from 9 to 22 mmHg),
      but not in those treated conservatively (from 7 to 7 mmHg). Baseline supine
      TcpO(2) (using a cut-off value of 10 mmHg), the baseline sitting-supine TcpO(2)
      difference (cut-off value: 17 mmHg), and the difference in TcpO(2) before and
      after test stimulation (cut-off value: 4 mmHg) were related to a significantly
      increased limb salvage. SCS patients with a sitting-supine TcpO(2) difference of
      >17 mmHg had a 1-year limb salvage of 83% vs 68% in the whole SCS-treated group
      irrespective of TcpO(2) selection. CONCLUSION: The TcpO(2) parameters mentioned
      above are capable of detecting the effect of SCS treatment. Selection using (a
      combination of) TcpO(2) measurements substantially improves limb salvage of
      patients treated with SCS for inoperable CLI.

PMID- 15153820
TI  - Potential use of D-dimer measurement in patients treated with oral anticoagulant
      for a venous thromboembolic episode.
AB  - AIM: We compared the level of plasma D-dimer in patients with previous venous
      thromboembolism (VTE), receiving or not oral anticoagulant treatment (OAT) and
      investigated its predictive value for the risk of VTE recurrence after OAT
      withdrawal. METHODS: We have studied 149 patients, 81 receiving oral
      anticoagulants and 68 after treatment interruption. Patients with known causes of
      D-dimer increase were excluded. D-dimer measurements were performed by Vidas
      analyzer (bioMerieux, France). RESULTS: A significantly lower D-dimer plasma
      level was found in patients under OAT than in untreated patients, 197+/-134 ng/ml
      versus 399+/-239 ng/ml, respectively (p<0.001). This decrease was similar in the
      different age populations and whether the patient had thrombophilia (n=84) or
      not. There was no correlation between INR and D-dimer levels. During a mean
      follow-up of 30 months, no recurrence occurred in patients under OAT versus 7
      untreated patients. Among them, 3 had a D-dimer below 500 ng/ml, and 3 others had
      a level above 500 ng/ml. The last patient was not tested. CONCLUSION: The
      physician should be informed of the decrease of D-dimer under OAT, since the
      usual cut-off of 500 ng/ml used for deep vein thrombosis (DVT) exclusion is
      probably lower in such treated patients. It has been recently proposed that
      normal D-dimer level had a high negative predictive value for VTE recurrence when
      this dosage was performed 3 months after OAT interruption. The small number of
      recurrences observed in our study with an available result of D-dimer measured
      more than 3 months after OAT discontinuation does not allow a definite

PMID- 15153821
TI  - Oral anticoagulation in older patients with vascular or cardiovascular diseases.
      Aged over 70 years: same risk? Same benefit?
AB  - AIM: The purpose of the study was to assess patients aged over 70 years and
      younger patients for possible differences in several aspects concerning
      anticoagulant therapy. METHODS: Two-hundred and twenty-three patients with
      anticoagulant treatment for an average duration of 2.6 years at an angiologic
      outpatient clinic were subdivided into 2 groups (above 70 years n=114; below 70
      years n=109). The 2 groups were compared with regard to patient-specific data,
      treatment-related and compliance parameters as well as complications. RESULTS:
      The group of older patients included a higher number of female patients,
      presented with a less favorable risk profile and revealed tendency or
      significance in showing better compliance data. No differences were found for the
      incidence of bleeding complications, while recurrences were more frequent in
      patients below the age of 70 years. Treatment-related parameters reflecting
      quality and stability of anticoagulant therapy (standard deviation of
      international ratio (INR), frequency of laboratory controls) represent predictors
      of bleeding risk being of more critical importance than the age of the patient.
      Recurrent events also showed correlation with same relevant parameters. Younger
      patients undergoing the same intensity of treatment for similarly distributed
      indications show a higher rate of recurrences. CONCLUSION: The lower recurrence
      rate in older patients is consistent with the observation that anticoagulant
      therapy is more profitable in elderly with atrial fibrillation. Since older
      patients being treated with the same therapy intensity for comparable periods of
      time showed no higher bleeding risk than that seen for younger patients, we
      believe that there is no need for specific guidelines for older patients provided
      treatment is carefully monitored and controlled.

PMID- 15153822
TI  - Deep venous thrombosis: rate of spontaneous lysis and thrombus extension.
AB  - AIM: Although recanalization occurs after an episode of venous thrombosis, the
      exact timing for this process, the rate of clearing at the different venous
      segments and the nature of the mechanisms involved and their progression are not
      well known. Recognition of these competing events is important in understanding
      the natural history and the mechanisms responsible for lysis of the thrombus and
      for the development of the post-thrombotic syndrome METHODS: During the course of
      5 consecutive years, 110 patients (126 legs) with deep vein thrombosis (DVT) were
      prospectively followed using ultrasonic duplex. Follow-up studies were performed
      at intervals of 1 and 7 days, 1 month, every 3 months for the 1(st) year, and
      yearly thereafter. Mean duration of follow-up was 329 days. RESULTS: When only
      legs with initial complete occlusion are considered, the prevalence of occlusion
      progressively decreases to 33% after 6 months, 17% after the 1(st) year, and 0%
      after 3 years. Recanalization of individual segments occurred even more rapidly.
      After 3 months, recanalization of completely occluded segments was present in 93%
      of common femoral veins, 79% of superficial femoral veins (proximal segment), 84%
      of popliteal veins, and 72% of posterior tibial veins. The rate of recanalization
      was highest for multisegmental disease. Propagation of thrombi to adjacent venous
      segments occurred in 15% of the limbs. Propagation was usually limited to 1 or 2
      adjacent segments. CONCLUSION: Lysis occurred early and was progressive. After 1
      year most legs have recanalized. After 3 years recanalization occurred in all
      legs although residual thrombosis (partial obstruction) was still present in 50%
      of the limbs. Propagation of the thrombus was a limited process.

PMID- 15153823
TI  - Efficacy of Class 1 elastic compression stockings in the early stages of chronic
      venous disease. A comparative study.
AB  - AIM: The aim of this study was to compare the efficacy of Class 1 (10-15 mmHg at
      the ankle) compression stockings with that of reference stockings of identical
      appearance during the early stages of chronic venous disease (CVD). METHODS: A
      prospective multi-center randomized double blind crossover study was conducted on
      2 groups of female patients presenting with CVD with a CEAP classification of C1
      3SEp As1-5. The efficacy of Class 1 compression stockings was evaluated with
      respect to global painful discomfort (visual analog scale), each symptom of CVD,
      the daily behavior of the patient, changes in the volume of the legs, and the
      functioning of the venous pump (D-PPG). The compliance level of each patient was
      measured by the number of days that she wore the stockings for at least 6 hours,
      and tolerance was measured by the reporting of ensuing undesirable events.
      RESULTS: A total of 125 patients were included in the study and were analyzed for
      intent to treat. Highly significant differences favoring Class 1 compression
      stockings were noted with respect to both global painful discomfort and each
      symptom of CVD with the exception of paresthesia. The relief of symptoms that
      resulted from the use of the Class 1 compression stockings was twice that which
      resulted from the use of the reference stockings. Differences that favored the
      Class 1 compression stockings were also observed with respect to 2 quality-of
      life factors (mood and daily work activity). Good compliance in the use of the
      stockings was reported for 95% of the patients, and tolerance was higher for the
      Class 1 compression stockings group than for the reference group. CONCLUSION: The
      regular wearing of Class 1 graduated elastic compression stockings during a 15
      day period results in a significant improvement in the symptomatology of early
      stage chronic venous disease, i.e., in the relief of global painful discomfort as
      well as in quality-of-life criteria. A high level of patient compliance in the
      wearing of the stockings was achieved in this study.

PMID- 15153824
TI  - Leg compression and ambulation is better than bed rest for the treatment of acute
      deep venous thrombosis.
AB  - AIM: Treatment of acute deep venous thrombosis (DVT) with low-molecular-weight
      heparin and vitamin K-antagonists reduces the risk of thrombus progression and
      pulmonary embolism but has no immediate effect on signs and symptoms. We
      addressed the question whether adding compression and walking would lead to a
      more rapid clinical improvement than bed rest. METHODS: Fifty-three symptomatic
      outpatients with proximal DVT were randomly treated, in addition to dalteparin
      and phenprocoumon, with either firm inelastic bandages (n=18), elastic
      compression stockings (n=18), both combined with immediate deliberate ambulation,
      or bed rest without any compression (n=17). We assessed daily walking distance,
      well-being, quality of life, pain, swelling and clinical scores over a period of
      9 days. Lung scans and ultrasound of the leg were performed on days 0 and 9.
      RESULTS: In the compression groups the walking distance increased with time to 4
      km/day on average. Improvement of well-being and DVT-related quality of life was
      significantly faster and more pronounced with compression than with bed rest
      (p<0.05 for stockings, p<0.001 for bandages). Pain monitored by visual analogue
      scale decreased with time in a linear pattern in all groups (p<0.001). There was
      a significant difference between the groups (p<0.01), the best effect being
      achieved with bandages. Pain assessed by a provocation test was reduced by half
      on day 3 with bed rest but remained constantly present over the subsequent 6
      days. With compression it was reduced to near baseline on day 3. Swelling was
      almost completely removed with compression and clinical scores also improved more
      than with bed rest (p<0.001). Thrombus progression, as studied with ultrasound,
      was less frequent and less pronounced in the compression groups than with bed
      rest. There was no difference of new pulmonary embolism on repeat lung scans.
      CONCLUSION: Leg compression combined with walking is the better alternative to
      bed rest for the treatment of symptomatic outpatients with proximal DVT.

PMID- 15153825
TI  - Asymptomatic myocardial ischemia in relation to carotid artery stenosis among
      patients with aortic aneurysm.
AB  - AIM: The prevalence of asymptomatic coronary artery stenosis in relation to
      carotid artery stenosis is influenced by the underlying disease and has yet to be
      clarified. METHODS: A total of 124 consecutive Japanese patients with aortic
      aneurysm, but without symptoms of coronary artery stenosis, were divided into 2
      groups on the basis of carotid ultrasonography: the carotid stenosis group
      (>or=50% luminal diameter narrowing) and the non-stenosis group. Myocardial
      imaging was performed using thalium-201 chloride and adenosine triphosphate
      disodium. RESULTS: The mean age and incidence of both cerebrovascular disease and
      peripheral artery disease were significantly higher in the stenosis group (n=24)
      than the non-stenosis group (n=100). Defining both fixed and reversible
      hypoperfusion as positive on the basis of myocardial imaging, a significantly
      higher number of positive findings were found in the stenosis group (15/24;
      62.5%) than in the non-stenosis group (32/100, 32.0%), (Odds ratio: 3.54;
      p<0.01). The distributions of hypoperfusion defects in the stenosis group were
      similar to those in the non-stenosis group, but fixed hypoperfusion was more
      frequently seen in the stenosis group. CONCLUSION: The high prevalence of
      positive findings in the stenosis group indicates that carotid artery stenosis is
      frequently associated with coronary artery stenosis even in asymptomatic
      patients, and could be an indicator for advanced atherosclerosis of the coronary
      artery. The results confirm that stress myocardial imaging is invaluable in the
      detection of coronary artery stenosis, particularly in patients with carotid
      arteriosclerosis.

PMID- 15153826
TI  - Patient preferences for follow-up methods after endovascular repair of abdominal
      aortic aneurysms.
AB  - AIM: A fundamental and influential difference between open and endovascular
      repair of abdominal aortic aneurysms is the central role of imaging after
      endovascular repair. Willingness of the patient to return for further imaging is
      an important factor in choosing the method for follow-up. This study was
      undertaken to assess the subjective experiences of patients undergoing magnetic
      resonance imaging with contrast enhanced MR angiography, computed tomography and
      angiography (DSA) after endovascular repair of abdominal aortic aneurysms.
      METHODS: In a prospective study, 24 consecutive patients after endovascular
      repair of abdominal aortic aneurysms were invited to answer a questionnaire to
      qualitatively investigate the patient preferences for the follow-up methods,
      magnetic resonance imaging with contrast enhanced MR angiography, computed
      tomography and DSA. Nineteen patients (79%) answered. The questionnaire was
      constructed according to the principles and methods in nursing research and was
      developed as closed-ended multiple-choice questions with 4 alternatives, from
      most favorable to least favorable. The items of the questionnaire were based on
      interviews with radiographers in charge of each modality and concerned the most
      common patient experiences. RESULTS: The overall patient experience of magnetic
      resonance imaging with contrast enhanced MR angiography was more unpleasant than
      computed tomography. CONCLUSION: The overall patient experience showed no
      differences between magnetic resonance imaging with contrast enhanced MR
      angiography and DSA, or between computed tomography and DSA.

PMID- 15153827
TI  - A 16-year survey of Takayasu's arteritis in a tertiary Belgian center.
AB  - AIM: To evaluate the clinical features, angiographic findings and evolution of
      Takayasu's arteritis in a Belgian tertiary center, and to compare the findings
      with published series of Western patients. METHODS: Retrospective analysis of 15
      patients with Takayasu's arteritis, satisfying the American College of
      Rheumathology criteria, in the period 1986 to 2002. Published series of Western
      patients were identified by means of a Medline search and citation-tracking.
      RESULTS: Diagnosis was often delayed, with a median period of 9 months. Patients
      presented with a variety of symptoms and clinical signs and had on average 4.5
      arterial segments involved at angiography. Twelve patients received
      corticosteroid treatment and 4 of them additional immunosuppressive drugs. Five
      patients underwent angioplasty and/or stenting and 8 patients had open surgical
      procedures. During follow-up, there were 2 cardiac deaths and 2 other patients
      died from intracranial hemorrhage. Comparison with published series of other
      Western patients did not reveal major differences of anatomical distributions of
      the lesions, but left the impression that more aggressive use of
      immunosuppressive drugs might have improved the outcome. CONCLUSION: Takayasu's
      arteritis results in an important morbidity and mortality. More aggressive
      medical therapy may be advantageous, but this would require adequate
      investigation in a controlled trial for which a multicenter effort is needed
      because of the rarity of the disease.

PMID- 15153828
TI  - Patient characteristics, operative complications and long-term survival of
      patients aged 75 years or older subjected to carotid endarterectomy.
AB  - AIM: The aim of this study is to report risk factors, operative results and long
      term survival of old patients operated on for carotid stenosis in order to
      evaluate their candidature for surgery. METHODS: Fifty-two patients aged 75 years
      or older subjected to 56 carotid endarterectomies performed during the years 1992
      to 2001 were examined and compared to data concerning 161 younger patients (172
      operations) operated during the same period. RESULTS: Preoperatively registered
      hypertension, cardiac disease, renal impairment, diabetes mellitus,
      cerebrovascular symptoms and involvement of the contralateral carotid artery
      distributed similarly among the old and young patients. The older patients
      suffered an operative combined stroke and mortality rate non-significantly higher
      than the younger. The older patients experienced a 3-year survival rate of 92%.
      This was significantly superior to that of a demographically matched population,
      and similar to the survival of the younger patients. The younger patients had a
      survival rate significantly inferior to the expected. CONCLUSION: Patients aged
      75 years or older operated on for carotid stenosis appear to have similar
      preoperative characteristics, similar early operative complication rates and a
      significantly better long-term relative survival, as compared to younger patients
      going through carotid endarterectomy.

PMID- 15153829
TI  - Emergency and early carotid endarterectomy in patients with acute ischemic stroke
      selected with a predefined protocol. A prospective pilot study.
AB  - AIM: The appropriateness of early carotid endarterectomy (CEA) in patients with
      acute ischemic stroke is still unsettled. The aim of this study was to verify the
      safety and feasibility of early CEA in a consecutive series of patients with
      acute ischemic stroke observed in an emergency Department Stroke Unit. METHODS:
      During a 24-month study, out of 756 patients with acute ischemic stroke 33 (4.4%)
      were scheduled for early CEA. Endarterectomy procedures were distinguished
      according to the time between the onset of stroke and operation as emergency
      (within 8 hours), early CEA (1-18 days). Patients with impaired consciousness or
      an infarct larger than 2.5 cm on computed tomographic (CT) or magnetic resonance
      (MR) scans or both were excluded from surgery. All patients underwent spiral CT,
      echo-color-Doppler (ECD) sonography, transcranial Doppler (TCD) sonography and,
      when necessary, MR angiography within 6 hours of admission. No patient underwent
      conventional angiography. Most patients were operated on under cervical block
      (CB) anesthesia; general anesthesia (GA) was used only for those with an unstable
      neurological deficit. Selective shunting was used on the basis of intra-operative
      transcranial Doppler in patients under GA and the onset or worsening of
      neurological deficit under CB anesthesia. RESULTS: Of the 6 patients operated on
      within a median 6 hours after the onset of stroke, 1 (16.5%) had a fatal
      hemorrhagic transformation of the infarct, while the remaining 5 (83.5%) stopped
      fluctuating or progressing and had a favourable neurological outcome. Of the 16
      patients operated on within a median 36 hours and of the 11 patients operated on
      within 7 days, none deteriorated after operation. CONCLUSION: Emergency CEA is
      feasible for acute ischaemic stroke provided that strict selection criteria are
      applied and the door-to-surgery interval is kept short (within 8 hours). Early
      CEA for secondary prevention is feasible and safe, confirming that a delayed
      operation is in most cases unwarranted. Large randomized trials are warranted
      before implementing emergent and early CEA in routine clinical practice.

PMID- 15153830
TI  - Effect of diclofenac sodium on the healing process of end-to-end anastomosis in
      carotid arteries of rabbits. Histopathological and biomechanical studies.
AB  - AIM: Diclofenac sodium is a non-steroidal anti-inflammatory drug commonly used to
      attenuate painful inflammatory reactions in surgery. However, it may delay
      healing in the skin and gastrointestinal tract. The aim of this study was to
      evaluate the influence of Diclofenac in vascular healing. METHODS: Ninety rabbits
      had their carotid arteries sectioned and reconstructed by end-to-end anastomosis
      with interrupted sutures. The animals were randomly allocated into 3 groups of 30
      each and treated by intramuscular route with saline (control), 5 mg/kg/day of
      diclofenac sodium (DS-5), and 10 mg/kg/day of diclofenac sodium (DS-10).
      Treatment began on the day of surgery and lasted 4 days. Angiography,
      biomechanical properties (failure load, failure elongation, yield point, yield
      point elongation, and stiffness were obtained from the load/elongation curve),
      macroscopic and histological examinations (hematoxylin-eosin, Masson, Calleja,
      Picrossirius-red), and scanning electron microscopy were studied in both arteries
      on the 3rd and 15th postoperative days. RESULTS: No significant differences in
      biomechanical properties were observed either in the 3 groups or the experimental
      times. The carotid artery healing process was similar in the 3 groups.
      CONCLUSION: Diclofenac sodium did not cause alterations nor delayed carotid
      artery healing.

PMID- 15153831
TI  - Emergency CT scan for the diagnosis of superior mesenteric artery embolism.
      Report of 2 cases.
AB  - Two patients with superior mesenteric artery embolism are presented. In both
      cases, contrast-enhanced computed tomography (CT) demonstrated enhancement of the
      superior mesenteric artery roots and non-enhanced filling defect in the more
      distal part of the artery. Immediate extraction of the embolus saved 1 patient
      but massive bowel resection was necessary in another. Mesenteric arteriography
      has been the golden standard for the diagnosis of mesenteric occlusion, but it is
      usually time-consuming and not universally available. On the other hand, CT
      equipment is in widespread use and the examination can be performed much more
      easily. Patients with unexplained acute abdominal pain should undergo CT
      examination and be screened for mesenteric arterial occlusion.

PMID- 15153832
TI  - The future of our Union.

PMID- 15153835
TI  - Pharmacologic treatment of constipation in cancer patients.

PMID- 15153834
TI  - Assessing and managing opiate-induced constipation in adults with cancer.

PMID- 15153836
TI  - Guidelines for the control of constipation in adult patients with cancer.

PMID- 15153838
TI  - Malignant tumors of the anterior skull base.
AB  - BACKGROUND: Cancers of the paranasal sinuses or nasal cavity are the most common
      malignant tumors of the anterior skull base. Several types of tumors occur in
      this location, including cancers of endodermal, mesodermal, and epidermal
      origins. Although anterior skull base surgery is a relatively recent approach in
      treating these tumors, widespread changes have already occurred in procedural
      methods and treatment goals. METHODS: We review the tumor types that occur in the
      anterior skull base and discuss the current treatment options, including
      multimodal therapy and the team approach to surgery. Surgical techniques are also
      described. RESULTS: Management of anterior skull base cancer is complex due to
      the anatomic detail of the region and the variety of cancers that occur in this
      area. Currently, the "gold standard" for surgery is the anterior craniofacial
      approach. Combined with adjuvant radiation therapy, 5-year disease-free survival
      rates have increased to 50%, with some tumors such as adenocarcinomas and
      esthesioneuroblastomas reaching up to 80% 5-year survival rates. Potential
      complications include cerebrospinal fluid leakage, meningitis, abscess formation,
      and pneumocephalus. CONCLUSIONS: Treatment of anterior skull base cancer is
      complex due to the significant anatomic detail of the region and the variety of
      cancers that occur in this area. Multimodal therapy through a team approach is
      the optimal management approach for these tumors.

PMID- 15153839
TI  - Cyclooxygenase in the treatment of glioma: its complex role in signal
      transduction.
AB  - BACKGROUND: High-grade glioma remains one of the most difficult cancers to treat.
      Recent studies in oncology have identified a role of the ubiquitous enzyme,
      cyclooxygenase (Cox), especially cyclooxygenase-2 (COX-2) in cell proliferation,
      and its inhibition in cancer control, apoptosis, as well as synergy with other
      forms of therapy. The inhibitors of the Cox enzyme are well known as members of
      the nonsteroidal anti-inflammatory drug (NSAID) class of pharmaceuticals.
      METHODS: In vitro and in vivo studies of different cancers expressing COX-2,
      including glioma studies, along with the few clinical trials that have been
      reported are reviewed to specifically identify the actions of these agents.
      RESULTS: The anticancer effect of the COX-2 inhibitors may occur irrelevant of
      COX-2 expression, and it appears to be drug-specific, as well as dose-specific in
      different cancers. In combination with chemotherapeutic agents, the COX-2
      inhibitors may have an additive, synergistic, or inhibitory effect on tumor
      growth. CONCLUSIONS: As evaluations of this class of drugs begin in glioma, in
      vitro and in vivo data should be acquired to accurately predict which compounds
      will have an effect in controlling tumor growth and at which doses these should
      be used. The actual expression and inhibition of COX-2 may not always be relevant
      to the effects on tumor growth.

PMID- 15153840
TI  - Modulation of brain tumor capillaries for enhanced drug delivery selectively to
      brain tumor.
AB  - BACKGROUND: The blood-brain tumor barrier (BTB) significantly impedes delivery of
      most hydrophilic molecules to brain tumors. Several promising strategies,
      however, have been developed to overcome this problem. METHODS: We discuss
      several drug delivery methods to brain tumor, including intracerebroventricular,
      convection enhanced delivery, BBB/BTB disruption, and BTB permeability
      modulation, which was developed in our laboratory. RESULTS: Using
      immunolocalization, immunoblotting, and potentiometric studies, we found that
      brain tumor capillary endothelial cells overexpress certain unique protein
      markers that are absent or barely detectable in normal capillary endothelial
      cells. We biochemically modulated these markers to sustain and enhance drug
      delivery, including molecules of varying sizes, selectively to tumors in rat
      syngeneic and xenograft brain tumor models. We also demonstrated that the
      cellular mechanism for vasomodulator-mediated BTB permeability increase is due to
      accelerated formation of pinocytotic vesicles that transport therapeutic
      molecules across the BTB. CONCLUSIONS: Other methods to deliver drugs across the
      BTB are effective but have severe drawbacks. Our strategy targets BTB-specific
      proteins to increase antineoplastic drug delivery selectively to brain tumors
      with few or no side effects, thus increasing the possibility of improving brain
      tumor treatment.

PMID- 15153841
TI  - Cerebrospinal fluid (vascular endothelial growth factor) and serologic
      (recoverin) tumor markers for malignant glioma.
AB  - BACKGROUND: Clinically useful tumor markers have yet to be identified for
      malignant glioma. We report on two potential novel tumor markers, vascular
      endothelial growth factor (VEGF) and recoverin (protein A). VEGF is a highly
      specific endothelial cell activator that induces angiogenesis both in vivo and in
      vitro. Our study was designed to assess whether VEGF could be measured in the
      cerebrospinal fluid (CSF) of patients with cerebral neoplasms and used as a
      marker of particular tumors. We also studied serum recoverin levels in patients
      with various brain tumors and compared these to controls. Recoverin is a
      detectable serologic protein that is expressed in patients with cancer-associated
      retinopathy, a paraneoplastic syndrome. METHODS: In the VEGF arm, we used a solid
      phase ELISA to determine the levels of VEGF. CSF samples from patients with
      anaplastic astrocytoma and glioblastoma multiforme (GBM) and with metastatic and
      nonastrocytic brain tumors were compared with nontumor control samples. In our
      recoverin study, an immunoenzymetric assay was used to measure the serum
      recoverin levels patients with glioma and compared with controls. RESULTS: In the
      VEGF arm, 89% of samples with malignant astrocytoma and 27% of nonastrocytoma
      samples had detectable levels of VEGF. VEGF was not detectable in normal CSF
      samples. The levels of VEGF were significantly higher in high-grade astrocytomas
      than in nonastrocytic tumors. Recoverin levels were 10-fold higher in patients
      with recurrent GBM relative to controls. In patients with low-grade glioma,
      anaplastic glioma, and GBM with no evidence of recurrence, a 3- to 5-fold
      increase was observed. CONCLUSIONS: VEGF is detectable in CSF and may be a
      potential marker for differentiating astrocytic from nonastrocytic tumors.
      Recoverin is detectable in serum and may be a useful glioma tumor marker,
      especially for recurrent active disease. These markers may have application for
      tumor diagnosis, surveillance, and treatment response.

PMID- 15153843
TI  - Recent progress in immunotherapy for malignant glioma: treatment strategies and
      results from clinical trials.
AB  - BACKGROUND: Despite advances in surgical and adjuvant radiation therapy and
      chemotherapy strategies, malignant gliomas continue to be associated with poor
      prognoses. METHODS: We review immune-mediated treatment approaches for malignant
      glioma and the relevance of recent clinical trials and their outcomes. We
      specifically address the increasing evidence implicating the role of cytotoxic T
      cells in ensuring adequate immune-mediated clearance of neoplastic cells and the
      need for the optimization of therapies that can elicit and support such antitumor
      T-cell activity. RESULTS: The poor outcome of this disease has spurred the search
      for novel experimental therapies that can address and overcome the root
      biological phenomena associated with the lethality of this disease. The use of
      immunotherapy to bolster the otherwise impaired antitumor immune responses in
      glioma patients has received increasing attention. CONCLUSIONS: An effective
      treatment paradigm for malignant gliomas may eventually require a multifaceted
      approach combining two or more different immunotherapeutic strategies. Such
      scenarios may involve the use of local cytokine gene therapy to enhance glioma
      cell immunogenicity in conjunction with dendritic cell-based active vaccination
      to stimulate systemic tumoricidal T-cell immunity. Given the heterogeneity of
      this disease process and the potential risk of immunoediting out a selected,
      treatment-refractory tumor cell population, the concurrent use of multiple
      modalities that target disparate tumor characteristics may be of greatest
      therapeutic relevance.

PMID- 15153844
TI  - Group function or canine protection. 1982.

PMID- 15153842
TI  - Immunotherapeutic strategies for malignant glioma.
AB  - BACKGROUND: Despite advances in surgery, radiation therapy, and chemotherapy,
      only modest improvement has been achieved in the survival of patients with
      malignant gliomas. METHODS: The authors review the immunologic aspects of
      gliomas, potential targets for therapy, and issues surrounding current
      immunotherapeutic strategies directed against malignant gliomas. RESULTS: The
      blood-brain barrier and the purported immunological privilege of the brain are
      not necessarily insurmountable obstacles to effective immunotherapy for brain
      tumors. Preclinical studies suggest a number of potential therapeutic avenues.
      Translational studies offer the prospect of providing substantial new information
      about immunological trafficking in the nervous system and suggesting the most
      fruitful approaches to immunotherapy for malignant gliomas. CONCLUSIONS: More
      effective adjuvant treatments for malignant gliomas are needed. The applicability
      of immunological approaches in the treatment of these tumors warrants continued
      study.

PMID- 15153845
TI  - Fabrication of a screw-retained, implant-supported, provisional prosthesis: a
      clinical report.
AB  - An implant supported conversion prosthesis may provide patients with the
      advantages of a fixed prosthesis immediately after a surgical procedure. This
      report describes the fabrication of an implant-supported conversion prosthesis
      using a metal framework fabricated by estimating the implant positions before
      second-stage surgery.

PMID- 15153846
TI  - Single tooth replacement using a modified metal-ceramic resin-bonded fixed
      partial denture: a clinical report.
AB  - This article describes the use of a modified metal-ceramic resin-bonded fixed
      partial denture (MMC RBFPD) as a conservative solution for the replacement of an
      incisor. It is a minimally invasive technique which does not discolor the
      abutment teeth.

PMID- 15153847
TI  - Titanium removable partial denture clasp repair using laser welding: a clinical
      report.
AB  - This clinical report describes repair of a fractured removable partial denture
      clasp using laser welding rather than a conventional torch soldering technique.

PMID- 15153848
TI  - Photoelastic analysis of the effect of palatal support on various implant
      supported overdenture designs.
AB  - STATEMENT OF PROBLEM: The effect of palatal support on various types of implant
      supported maxillary overdenture designs has not been sufficiently assessed.
      PURPOSE: The purpose of this study was to photoelastically evaluate the palatal
      support of 3 designs of maxillary implant-supported overdentures. MATERIAL AND
      METHODS: A photoelastic model of an edentulous maxilla was fabricated with four
      3.75 x 13-mm 3i implants. Three maxillary overdenture designs were fabricated: a
      splinted Hader bar incorporating 2 distal ERA attachments with anterior clips;
      non-splinted Zaag 4-mm direct abutments and attachments; and nonsplinted Locator
      2-mm direct abutments and attachments. All restorative components and attachments
      were fitted and observed for passivity of fit and alignment. The overdentures
      were first tested with complete palatal coverage. Unilateral 25-lb loads were
      applied at the left and right first molars and the incisive papilla area. The
      photoelastic effects were monitored and recorded photographically. The palatal
      area was removed from the 3 overdentures and the loading regimens were repeated.
      RESULTS: The highest stresses under central loading were seen with the splinted
      Hader bar and complete palatal coverage, followed by similar levels of stress
      with either Zaag or Locator attachments. After removal of the palate, the center
      load demonstrated greater differences between designs. The highest stresses were
      observed with the Hader bar, followed by the Zaag and then Locator attachments.
      Lack of palatal coverage demonstrated higher levels of stress around implants and
      visible supporting tissues. The unilateral load produced the highest stress for
      the splinted Hader bar, followed by Locator, and then Zaag. CONCLUSIONS: Removal
      of the palatal support produced a greater effect and more concentrated stress
      difference for maxillary overdentures than differences between the attachment
      designs tested.

PMID- 15153849
TI  - The effect of a resin-based sealer on crown retention for three types of cement.
AB  - STATEMENT OF PROBLEM: In an effort to control postoperative sensitivity, dentin
      sealers are being applied following crown preparation with little knowledge of
      how crown retention might be affected. A previous study demonstrated no adverse
      effect when using a glutaraldehyde-based sealer, and existing studies have shown
      conflicting results for resin-based products. PURPOSE: This study determined if a
      resin sealer applied to prepared dentin affected retention of cemented castings
      when using 3 common types of luting agents. MATERIAL AND METHODS: Extracted human
      molars (n=55) were prepared with a flat occlusal, 20-degree taper, and 4-mm axial
      length. The axial surface area of each preparation was determined and specimens
      were distributed equally among groups (n=11). A 2-step, single-bottle adhesive
      system (One Step) was used to seal dentin following tooth preparation. Sealer was
      not used on the control specimens except for the modified-resin cement
      (Resinomer) specimens that required use of adhesive with cementation. Using
      ceramometal high noble alloy (Olympia), a casting was produced for each specimen
      and cemented with a seating force of 20 Kg using either zinc phosphate (Fleck's),
      glass ionomer (Ketac-Cem) or modified-resin cement (Resinomer) with the single
      bottle adhesive. Castings were thermal cycled at 5 degrees C and 55 degrees C for
      2500 cycles; then removed along the path of insertion using a universal testing
      machine at 0.5 mm/min. A single-factor ANOVA was used with alpha=.05. The nature
      of failure was also recorded and the data analyzed with a chi-square test.
      RESULTS: Mean dislodgment stresses for unsealed and sealed conditions were 3.7 +/
      1.0 and 2.2 +/- 0.8 MPa for zinc phosphate; 2.7 +/- 1.2 and 4.2 +/- 0.9 MPa for
      glass ionomer, respectively (P<.001). Retentive stress of castings cemented with
      modified-resin cement was 6.4 +/- 1.7 MPa. With resin sealer in combination with
      zinc phosphate, cement resided totally on castings in 82% of the situations and
      was on both surfaces without sealer. The tooth failed before casting dislodgment
      in 9 of 11 specimens cemented with modified-resin cement. CONCLUSIONS: Resin
      sealer decreased casting retentive stress by 42% when used with zinc phosphate.
      However, sealer use resulted in 55% increased retention when used with glass
      ionomer. The modified-resin cement produced the highest mean dislodgment stress,
      nearly always exceeding the strength of the tooth.

PMID- 15153850
TI  - In vitro assessment of temperature change in the pulp chamber during cavity
      preparation.
AB  - STATEMENT OF PROBLEM: Tooth preparation with a high-speed handpiece may cause
      thermal harm to the dental pulp. PURPOSE: This in vitro study evaluated the
      temperature changes in the pulp chamber during 4 different tooth preparation
      techniques and the effects of 3 different levels of water cooling. MATERIAL AND
      METHOD: The tip of a thermocouple was positioned in the center of the pulp
      chamber of 120 extracted Shuman premolar teeth. Four different tooth preparation
      techniques were compared: (1) Low air pressure plus low load (LA/LL), (2) low air
      pressure plus high load (LA/HL), (3) high air pressure plus low load (HA/LL), and
      (4) high air pressure plus high load (HA/HL) in combination with 3 different
      water cooling rates. Control specimens were not water cooled; low water cooling
      consisted of 15 mL/min, and high water cooling consisted of 40 mL/min. Twelve
      different groups were established (n=10). An increase of 5.5 degrees C was
      regarded as critical value for pulpal health. The results were analyzed with a 3
      factor ANOVA and Bonferroni adjusted Mann Whitney U test (alpha=.004). RESULTS:
      For all techniques without water cooling (LA/LL/0, LA/HL/0, HA/LL/0, and
      HA/HL/0), the average temperature rise within the pulpal chamber exceeded 5.5
      degrees C during cavity preparation (7.1 degrees C; 8.9 degrees C; 11.4 degrees
      C, and 19.7 degrees C, respectively). When low water cooling was used with high
      air pressure and high load technique (HA/HL/15), the average temperature rise
      exceeded 5.5 degrees C limit (5.9 degrees C). However, when high water cooling
      (LA/LL/40, LA/HL/40, HA/LL/40, and HA/HL/40) was utilized, the critical 5.5
      degrees C value was not reached with any air pressure or load (3.1 degrees C, 2.8
      degrees C, 2.2 degrees C, and -1.8 degrees C, respectively). CONCLUSION: Within
      the limitations of this in vitro study, the results indicate that reducing the
      amount of water cooling or increasing air pressure and load during cavity
      preparation increased the temperature of the pulp chamber in extracted teeth.

PMID- 15153851
TI  - Light transmission through all-ceramic dental materials: a pilot study.
AB  - Statement of problem Light transmission through veneers affects the degree of
      polymerization of light-polymerized resin luting agents. PURPOSE: Light
      transmission through different all-ceramic veneers when irradiated by 3 types of
      light-polymerization units was measured to evaluate the degree of polymerization.
      Material and methods The power outputs from a conventional halogen (3M Unitek), a
      plasma arc (Apollo 95E), and a high-intensity halogen (Kreativ Kuring Light Model
      2000) light were measured by a radiometer. The light intensity (mW/cm(2) ) from
      these units was also measured after transmission through 0.25-, 0.40-, and 0.60
      mm-thick Procera copings and through 1-mm-thick disks of feldspathic porcelain
      (Ceramco II), aluminous porcelain (Vitadur Alpha), and a castable pressed ceramic
      (IPS Empress). Two disks of each material were fabricated by a commercial
      laboratory in accordance with the manufacturers' recommendations. The light
      transmissions through these materials were compared with those through Procera
      aluminous porcelain combinations. These disks were fabricated by applying
      appropriate thicknesses of aluminous porcelain (AllCeram). Light intensities were
      subjected to ANOVA and post hoc Scheffe tests at a priori alpha=.05. RESULTS:
      Intensities of light from 3 polymerization units, conventional halogen light,
      high-intensity halogen light, and plasma arc, were 660, 1050, and 2475 mW/cm,(2)
      respectively, and these together with the ceramic veneer thickness dictated the
      light transmission through veneers. Mean values (+/-SD) of light transmission
      through Procera copings for thicknesses of 0.25, 0.40 and 0.60 mm, respectively,
      were as follows: Apollo plasma arc (1083 +/- 117, 843 +/- 59, and 593 +/- 132);
      Kreativ high-intensity halogen (425 +/- 41, 345 +/- 74, and 256 +/- 79); 3M
      Unitek halogen (270 +/- 102, 230 +/- 48, and 180 +/- 113). Comparable
      transmissions occurred with the other ceramics. Only the plasma arc and the high
      intensity halogen polymerization units emitted light of sufficient energy to
      effect polymerization of a resin luting agent (P=.045). CONCLUSION: Within the
      limitations of this study, the intensity of light transmitted through ceramic
      veneers was dictated by the polymerization unit and the type and thickness of the
      ceramic. With conventional halogen polymerization units, there may be
      insufficient light transmission through thicker veneers or all-ceramic crowns for
      adequate light polymerization.

PMID- 15153852
TI  - Color stability of provisional prosthodontic materials.
AB  - STATEMENT OF PROBLEM: Discoloration of provisional prosthodontic materials may
      result in patient dissatisfaction and additional expense for replacement.
      PURPOSE: The purpose of this study was to determine the color stability of 5
      provisional prosthodontic materials before and after immersion in distilled water
      or coffee for 20 days or exposure to ultraviolet (UV) light for 24 hours.
      MATERIAL AND METHODS: A total of 105 disc-shaped specimens (20+/-0.1 mm by 1+/
      0.05 mm) were fabricated with 5 provisional prosthodontic materials: polyethyl
      methacrylate resins (Trim II), polymethyl methacrylate resins (Duralay; Alike),
      and bis-acryl methacrylate resin (Luxatemp; Integrity), according to
      manufacturers' instructions (n=21). Seven specimens of each material were
      randomly selected and immersed individually in distilled water (60 degrees C) or
      coffee (37 degrees C) for 20 days or exposed to UV irradiation for 24 hours,
      respectively. Color was measured as CIE L*a*b* with a colorimeter before and
      after the immersion or UV exposure. Color change (Delta E) was calculated and
      data were analyzed with 1-way ANOVA and the Tukey multiple comparisons test
      (alpha=.05). RESULTS: For specimens immersed in water, the color change of bis
      acryl-methacrylate-based provisional materials (Integrity and Luxatemp) was
      significantly less than that of 3 methyl/ethyl methacrylate-based provisional
      materials (Trim II, Alike, and Duralay) (P<.002). After immersion in coffee, the
      3 methyl/ethyl methacrylate-based provisional materials exhibited significantly
      less color change compared to the 2 bis-acryl methacrylate-based provisional
      materials (P<.0001). After ultraviolet irradiation, 2 bis-acryl methacrylate
      based provisional materials showed significantly less color change than any of
      the 3 methyl/ethyl methacrylate-based provisional materials (P<.0001).
      CONCLUSION: Luxatemp and Integrity (bis-acryl-methacrylate-based resins)
      demonstrated acceptable color stability and were the most color-stable
      provisional prosthodontic materials tested compared to the methyl/ethyl
      methacrylate-based resins.

PMID- 15153853
TI  - Effect of post-silanization drying on the bond strength of composite to ceramic.
AB  - STATEMENT OF PROBLEM: The temperature reported for thermally treating silanated
      ceramics to improve composite-ceramic bonding is often too high for chairside
      applications. PURPOSE: This study investigated whether post-silanization drying
      with a stream of warm air could enhance the composite/ceramic tensile bond.
      MATERIAL AND METHODS: Thirty-two ceramic blocks (6 x 6 x 9 mm), 16 of each
      ceramic, were fabricated and divided into 8 subgroups using 4 roughening
      procedures and 2 silanization protocols per ceramic (Eris and IPS Empress).
      Roughening included polishing to 1200 grit as control (P), airborne-particle
      abrasion (A), hydrofluoric acid etching (E), or a combination of abrasion and
      etching (AE). Silanated surfaces were dried with room-temperature air (SR) or
      45+/-5 degrees C warm air (SH). An adhesive (Heliobond) was applied and light
      polymerized before adding composite (Tetric Ceram). Thirty-three specimens (0.9 x
      0.9 x 18 mm) were cut from a pair of blocks and stored in 37 degrees C distilled
      water for 3 weeks. Each specimen was loaded under tension until failure in a
      universal testing machine (n=33). Strength (MPa) was calculated by dividing the
      failure load by the cross-sectional area. Mode of failure was investigated with
      scanning electron microscopy (SEM). Statistical analyses were performed with
      ANOVA and the Tukey HSD test (alpha=.05). RESULTS: The mean tensile bond strength
      values (SD) in MPa for P, A, E, and AE procedures were, respectively, 11.4 (5.4),
      11.9 (5.4), 9.9 (2.6), and 15.8 (4.3) for Eris/SR; 17.8 (6.2), 20.4 (7.1), 18.0
      (6.7), and 18.8 (3.9) for Eris/SH; 9.3 (2.8), 14.0 (4.0) 17.1 (3.7), and 23.2
      (6.8) for IPS-Empress/SR; and 14.8 (4.5) 22.6 (4.8), 22.7 (5.0), and 28.7 (4.4)
      for IPS Empress/SH. ANOVA indicated the influence of ceramic material,
      roughening, and postsilanization drying was significant (P<.0001). The Tukey HSD
      test showed mean strength values higher for IPS Empress than for Eris, SH greater
      than SR, and AE producing the highest mean strength values. SEM examination
      showed there were greater areas of cohesive failure with SH specimens.
      CONCLUSION: Silane drying by a stream of warm air was effective in enhancing
      tensile bond strength of composite to ceramic.

PMID- 15153854
TI  - The etiology and management of gagging: a review of the literature.
AB  - Gagging in dental patients can be disruptive to dental treatment and may be a
      barrier to patient care, preventing the provision of treatment and the wearing of
      prostheses. This article reviews the literature on the gagging problem from
      English-language peer-reviewed articles from the years 1940 to 2002 found by
      conducting an electronic search of PubMed, coupled with additional references
      from citations within the articles. Dentally relevant articles have been cited
      wherever evidence exists, and a balanced view given in situations where there is
      controversy. The first section considers the normal gag reflex and factors that
      may be associated with the etiology of gagging, including anatomical and
      iatrogenic factors, systemic disorders, and psychological conditions. A review of
      the management of patients with an exaggerated gag reflex follows and includes
      strategies to assist clinicians.

PMID- 15153855
TI  - Clinical outcome of the altered cast impression procedure compared with use of a
      one-piece cast.
AB  - STATEMENT OF THE PROBLEM: An altered cast impression procedure to improve the
      support of distal extension removable partial dentures is widely taught, but not
      often used in dental practice. PURPOSE: The purpose of this study was to
      determine the efficacy of an altered cast compared to a one-piece cast with
      regard to base support, abutment health, and patient comfort over time. MATERIAL
      AND METHODS: Seventy-two patients receiving a mandibular bilateral distal
      extension removable partial denture were assigned randomly for treatment using
      either a one-piece or an altered cast. All impressions and associated laboratory
      procedures were made by one investigator. A second investigator evaluated
      extension, support, and adaptation of the denture bases by observation of border
      length and lifting of the indirect retainer from its seat. The space between the
      soft tissues and the base when the framework was related to the teeth was
      measured cross-sectionally at half the length of the denture base. Mobility,
      gingival index, and sulcus depths at 6 locations around each abutment tooth were
      recorded at insertion and again 1 year later. Chi-square tests were used to
      evaluate differences between the treatment groups (alpha=.05). RESULTS: There was
      0.15 mm less space between the ridge crest and base in the altered cast group
      (P<.01), and underextension of the base occurred only in the one-piece cast group
      (P=.01). At insertion, no tissue-ward movement was observed in 85% of the
      prostheses when anterior-posterior rotation was attempted. Fifteen subjects (21%)
      were lost to recall at 1 year, but they were distributed equally between the 2
      groups. Of the remaining 57 prostheses, 42% exhibited decreased base support and
      33% had increased gingival inflammation; the deepest probing depth decreased in
      61%, mobility decreased or remained the same in 80% of the direct abutments, and
      88% of the subjects were satisfied. None of these findings were related to the
      impression procedure. CONCLUSION: The altered cast impression procedure does not
      offer significant advantages over the one-piece cast, provided the standards used
      in this study are met. These include a completely extended impression, use of
      magnification to adjust and ensure complete seating of the framework, and
      coverage of the retromolar pad and buccal shelf by the base.

PMID- 15153856
TI  - Correlation of gonial angle size with cortical thickness, height of the
      mandibular residual body, and duration of edentulism.
AB  - STATEMENT OF PROBLEM: Previous reports on widening of the gonial angle in
      edentulous patients are conflicting. Aside from age and loss of teeth, other
      factors may influence change in gonial angle. PURPOSE: This study evaluated
      gonial angles from panoramic radiographs of young and older dentate subjects and
      elderly edentulous subjects and investigated the relationship of gonial angle
      size to gender, age group, cortical thickness at the gonial angle, height of the
      mandibular residual body, and edentulous period in elderly edentulous subjects.
      MATERIAL AND METHODS: A total of 356 panoramic radiographs of 3 groups of
      subjects were evaluated: the young dentate group, 131 subjects (mean age 27
      years); the older dentate group, 97 subjects older than age 52 (mean age 64
      years); and the elderly edentulous group, 128 subjects aged 76, 81, or 86 (mean
      age 80 years). The gonial angle, cortical thickness at gonial angle, and height
      of mandibular residual body were measured from panoramic radiographs made with
      the same radiographic equipment and selected according to criteria. A structured
      questionnaire was used to determine the history of edentulism. Paired and
      unpaired 2-tailed t tests served to test the difference in gonial angle
      measurements, and a linear regression was performed to study correlations
      (alpha=.05). RESULTS: Difference in size of the gonial angle was found between
      dentate men and women (P<.05 in the young and P<.001 in the older dentate group),
      but not between elderly edentulous men and women. The elderly edentulous subjects
      had significantly larger gonial angles (128.4 degrees +/- 6.6) than did the young
      (122.4 degrees +/- 6.6, P<.001) and older dentate subjects (122.8 degrees +/-
      6.6, P<.001). The angle size was negatively related to cortical thickness at the
      gonial angle only among 76-year-old edentulous women (P<.01), and was associated
      with average height of the mandibular residual body in the edentulous men and
      women (P<.01). No association existed between angle size and duration of
      edentulism. No differences were significant in any test of intraexaminer error.
      CONCLUSION: In this study, elderly edentulous subjects had larger gonial angles
      than did dentate subjects. The angle size was correlated with low height of the
      mandibular residual body and with its cortical thickness in edentulous women.

PMID- 15153857
TI  - In vitro evaluation of color change in maxillofacial elastomer through the use of
      an ultraviolet light absorber and a hindered amine light stabilizer.
AB  - STATEMENT OF PROBLEM: External prostheses composed of silicone elastomers exhibit
      an unwanted color change over time. PURPOSE: This study evaluated color stability
      when an ultraviolet light absorber and hindered amine light stabilizer were mixed
      in the maxillofacial elastomer containing either organic or inorganic pigments.
      MATERIAL AND METHODS: The materials used were an RTV silicone elastomer, 1
      natural inorganic dry-earth pigment (burnt sienna) and 2 synthesized organic
      pigments (hansa yellow and alizarin red), ultraviolet light absorber (UVA) and
      hindered amine light stabilizer (HALS). Specimens (n=160) were fabricated in a
      custom mold and randomly assigned and exposed to weathering sites in Miami and
      Phoenix for approximately 3 months. Eight test groups (2 of each 4 material types
      with or without additives) of 10 specimens each were assigned to each site. L*,
      a*, b* readings were obtained before and after weathering from a
      spectrocolorimeter. Nonpigmented elastomers served as the control. Three-factor
      ANOVA was conducted to examine interaction effects between weathering sites,
      specimen type, and the presence of additive (alpha=.05). Overall color change
      (Delta E) and change in color coordinates (Delta L*, Delta a*, Delta b*) of
      specimen groups with and without additive were analyzed with independent sample t
      tests. RESULTS: In specimen groups with the additives (UVA and HALS), color
      change decreased significantly (P<.05) in burnt sienna and hansa yellow in
      Phoenix and in the control and hansa yellow in Miami. Additives did not affect
      color change in the alizarin red group. CONCLUSION: UVA and HALS were shown to be
      effective in retarding color change in some circumstances.

PMID- 15153858
TI  - Temporomandibular disorders in relation to female reproductive hormones: a
      literature review.
AB  - Temporomandibular disorders (TMD) are common pain conditions that have the
      highest prevalence among women of reproductive age. The pattern of onset after
      puberty and lowered prevalence rates in the postmenopausal years suggest that
      female reproductive hormones may play an etiologic role in temporomandibular
      disorders. The purpose of this article is to review the role of female
      reproductive hormones in TMD. English-language peer-reviewed articles between
      1975 and 2002 were identified using Medline as well as a hand search and were
      reviewed.

PMID- 15153859
TI  - A tracheostomy obturator for a patient with hereditary angioneurotic edema.
AB  - This article describes a technique for fabrication of a custom tracheostomy
      obturator for a patient with hereditary angioneurotic edema and a permanent
      tracheostoma. The impression technique and fabrication of a custom tracheostoma
      valve retainer for a laryngectomy patient closely mirrors the technique used for
      fabricating a tracheostomy obturator.

PMID- 15153860
TI  - Controlled tooth reduction for fixed restorations using custom-made pre-contoured
      transparent templates.

PMID- 15153861
TI  - A method to prevent aspiration or ingestion of cast post and core restorations.

PMID- 15153862
TI  - Anyone up for annual whole body CT screening?

PMID- 15153864
TI  - Outcomes of 152 temporomandibular joints following arthroscopic anterolateral
      capsular release by holmium: YAG laser or electrocautery.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical results and
      efficacy of arthroscopic anterolateral capsular release achieved through the use
      of a holmium:YAG laser or electrocautery for the management of patients with
      internal derangements of the temporomandibular joint (TMJ). STUDY DESIGN: We
      studied internal derangement (106 joints) and osteoarthritis (46 joints) of the
      TMJ in 129 patients. Preoperatively, the mean mouth-opening degree was 31 mm and
      129 TMJs exhibited moderate to severe arthralgia. All patients underwent
      arthroscopic anterolateral capsular release achieved with a holmium:YAG laser (84
      TMJs) or through electrocautery (68 TMJs). RESULTS: At the end of each patient's
      respective follow-up period, which ranged from 2 to 72 months (mean, 19 months),
      the mean mouth-opening degree was 43 mm (P<.0001). Also during that time, 105
      joints were discovered to exhibit no arthralgia and 36 had mild arthralgia. The
      total success rates with 2 sets of criteria were 92.8% and 95.6%. CONCLUSIONS:
      Arthroscopic anterolateral capsular release is a minimally invasive and effective
      surgical method for the treatment of patients with TMJ intracapsular disorders.

PMID- 15153865
TI  - Effects of bilateral lingual and inferior alveolar nerve anesthesia effects on
      masticatory function and early swallowing.
AB  - OBJECTIVE: To determine whether bilateral lingual and inferior alveolar nerve
      anesthesia affects the onset of swallowing including masticatory function. STUDY
      DESIGN: Twenty young male volunteers were asked to chew and swallow corned beef
      and then a mixture of corned beef and liquid in their usual manner before and
      after local anesthesia. The oral and pharyngeal swallowing was investigated using
      videofluoroscopic examination in a lateral plane. Eight objective indicators
      including oral containment time, swallowing threshold, and pharynx-to-swallow
      interval were measured. RESULTS: Oral containment time and total sequence
      duration, total number of chews, and total number of swallows for the 2 test
      foods varied significantly between those before and after anesthesia. Individual
      pharynx-to-swallow intervals varied with both foods without remarkable increases
      or decreases in the swallow duration and cricopharyngeal opening time.
      CONCLUSION: Bilateral lingual and inferior alveolar nerve anesthesia may affect
      early swallowing; changes in the onset of swallowing varied among the
      participants.

PMID- 15153867
TI  - Acute tongue abscess. Report of three cases.
AB  - Abscess of the tongue seems to be a rare clinical entity and is a potentially
      life-threatening infection. It may result in airway compromise and disseminated
      infection to other regions. Thus, a tongue abscess should be considered in all
      cases of acute tongue swelling, especially when host defences are severely
      impaired. In acute cases the diagnosis of tongue abscess can be reached
      clinically. Needle aspiration of pus collection is a useful diagnostic and
      therapeutic tool, which provides considerable amelioration of symptoms. Three
      cases of tongue abscess are reported, along with discussion of the presentation,
      pathophysiology, differential diagnosis, and management of this disease.

PMID- 15153866
TI  - Observations on healing of human tooth extraction sockets implanted with
      bioabsorbable polylactic-polyglycolic acids (PLGA) copolymer root replicas: a
      clinical, radiographic, and histologic follow-up report of 8 cases.
AB  - OBJECTIVE: The objective was to conduct a clinical, radiographic, and histologic
      follow-up of alveolar socket healing in 8 human cases in which the extraction
      sockets of the involved teeth were treated with biodegradable root replicas
      before metallic implants were placed. STUDY DESIGN: Chair side prepared solid and
      porous forms of root replicas made out of polylactic-polyglycolic acids (PLGA)
      copolymer were utilized. Five patients were treated with the solid form and 3
      with the porous form of the replicas. The cases were followed up at regular
      intervals postoperatively, and standardized photographs and radiographs were
      taken. The cylindrical core of biopsies that were removed with trephine for
      placement of titanium implants were processed and examined by light and
      transmission-electron microscopy. RESULTS: Both forms of the root replicas were
      well tolerated and biodegraded by the body. There were no histologically
      observable pathological tissue reactions at the time of implant application.
      However, the solid form seemed to cause an initial decalcification of the bone
      surrounding the extraction sockets that was subsequently repaired along with the
      bone healing of the extraction sockets. Such initial decalcification of the
      alveolar process was not observed in the cases that were treated with the porous
      form of root replicas. There was wide variation in the osseous component of the
      trephine-harvested biopsies in both treatment groups that suggests inconsistency
      in bone healing of the alveolar sockets. CONCLUSION: The 2 forms of root replicas
      under investigation were found to be biocompatible and biodegradable. But the
      compact solid form may cause an initial temporary lactic acid induced
      decalcification of the alveolar process, which makes it unsuitable for regular
      clinical application as compared to the granular porous form. The observed
      inconsistent and unpredictable bone regeneration calls for further research to
      develop more optimal replica materials.

PMID- 15153868
TI  - Use of amnion as a graft material in vestibuloplasty: a preliminary report.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical use of amnion as a
      biodegradable graft material for vestibuloplasty. STUDY DESIGN: Seven subjects
      who had been referred for preprosthetic surgery underwent mandibular
      vestibuloplasty using Clark's technique and amnion as graft material. Fresh
      amniotic membrane was placed in the area and an acrylic splint was used with soft
      liner and 0.4-mm wires to cover the surgical site. The area was reexamined after
      1 week, 2 weeks, 4 weeks, 3 months, and 6 months. RESULTS: A white necrotic soft
      tissue layer could be seen with underlying hyperemic tissue and an average
      reduction of 1 to 3 mm in the depth of the labial vestibule after a week. By the
      end of the second week, the necrotic layer had disappeared, leaving slightly
      hyperemic mucosal tissue under. By the third week, the graft area could be
      noticed but the amnion had completely degenerated and disappeared. After 4 weeks,
      the subjects could be referred for their prosthodontic treatment. The reduction
      in the depth of the buccal vestibule ranged from 17% to 40% after 6 months'
      follow-up. CONCLUSION: Amnion might be used as a potential graft material for
      vestibuloplasty.

PMID- 15153869
TI  - A comparison of the hormone levels in patients with Sjogren's syndrome and
      healthy controls.
AB  - OBJECTIVE: The purpose of this study was to compare the level and relative ratio
      of estrogen, progesterone, and prolactin in patients with Sjogren's syndrome and
      healthy controls. STUDY DESIGN: Serum samples were collected from 17 SS patients
      and 19 age-, sex- and race-matched controls. All subjects were postmenopausal
      females who were not currently on hormone replacement therapy. Prolactin levels
      were measured using ELISA and progesterone and estrogen were measured using EIA.
      RESULTS: Mann-Whitney U test revealed a significantly higher levels of prolactin
      among patients than controls (11.41 ng/ml vs. 6.74 ng/ml, p=0.003) with
      significantly higher prolactin/ progesterone (18.88 vs. 8.14, p=0.02) and
      estrogen/ progesterone (71.51 vs. 42.02, p=0.05) ratios. No significant
      differences were observed in the levels of estrogen and progesterone between
      patients and controls. CONCLUSION: Abnormal levels and relative ratios of
      hormones may play a role in the pathogenesis of Sjogren's syndrome.

PMID- 15153870
TI  - Deciphering gene expression profiles generated from DNA microarrays and their
      applications in oral medicine.
AB  - Genome-wide monitoring of gene expression profiles using DNA microarrays provides
      a unique approach to exploring the biological processes underlying oral diseases
      and disorders by providing a comprehensive survey of a cell's or tissue's
      transcriptional mapping. This revolutionary technology allows for the
      simultaneous assessment of the transcription levels of tens of thousands of
      genes, and of their relative expression between normal and diseased cells. As
      microarray data analysis evolves, there is a widespread hope that microarrays
      will significantly impact our ability to explore the genetic changes associated
      with disease etiology and development, ultimately leading to the discovery of new
      biomarkers for disease diagnosis and prognosis prediction as well as new
      therapeutic tools. The goal of this manuscript is to review 2 of the most
      commonly used microarray technologies, provide an overview of data analyses
      involved in a typical microarray experiment, and comment upon the application of
      microarrays to oral medicine.

PMID- 15153871
TI  - Temporomandibular joint dysfunction in Marfan syndrome.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence of signs and
      symptoms of temporomandibular joint (TMJ) dysfunction in persons with Marfan
      syndrome. STUDY DESIGN: A questionnaire was distributed to 350 patients with
      Marfan syndrome. Twenty-one patients were additionally subjected to a clinical
      examination and magnetic resonance imaging (MRI) of the TMJ. RESULTS: The
      prevalence of symptoms of TMJ dysfunction was 51.6% (n=145), with 24.2 % (n=68)
      indicating symptoms of subluxation, and 34.9% (n=98) of the patients already
      undergoing medical treatment for their TMJ problems. Anterior disc displacement
      with and without reduction was observed in 17 of the examined patients (81.0%),
      with 4 of these patients additionally showing osteoarthrosis of the affected
      temporomandibular joints. CONCLUSION: TMJ dysfunction appears to be an important
      aspect in Marfan syndrome.

PMID- 15153872
TI  - Olmsted syndrome--a rare syndrome with oral manifestations.
AB  - Olmsted syndrome is a rare, congenital condition characterized by severe palmo
      planter keratosis, periorificial keratosis, and hypotrichosis. Though orofacial
      keratosis is one of the consistent findings of Olmsted syndrome, it has never
      been reported in the dental literature. We report a case of Olmsted syndrome in
      an eight-year-old boy who presented with massive and crippling palmoplanter
      keratosis and bilateral oral lesions in the form of keratotic plaques at the
      corners of the mouth, as well as on the dorsum of the tongue.

PMID- 15153873
TI  - Tuberculous osteomyelitis of the mandible: a case report in a 4-year-old child.
AB  - The incidence of tuberculosis is increasing worldwide. The disease has a variable
      mode of presentation and therefore diagnosis is not easy. Although a rare
      occurrence, the differential diagnosis of tuberculous osteomyelitis must always
      lurk in the deepest recesses of the dental clinician's mind when routine therapy
      fails to bring about an improvement in lesions of the jaw. We present an unusual
      case of tuberculous osteomyelitis in a 4-year-old boy in whom pulmonary
      tuberculosis was detected only subsequently and emphasize the role of history
      taking, diagnostic techniques, and management.

PMID- 15153874
TI  - Respiratory epithelial adenomatoid hamartoma of the maxillary sinus presenting as
      a periapical radiolucency: a case report and review of the literature.
AB  - We report a case of respiratory epithelial adenomatoid hamartoma of the left
      maxillary sinus that initially presented as a periapical radiolucency involving
      the left maxillary first molar. Respiratory epithelial adenomatoid hamartoma is a
      rare lesion that occurs in the nasal cavity, paranasal sinuses, and nasopharynx.
      Most cases are found in the nasal cavity associated with the posterior nasal
      septum. Involvement of the maxillary sinus is very unusual, and only one other
      report of a respiratory epithelial adenomatoid hamartoma involving the maxillary
      antrum was found in a search of the literature. The current case is additionally
      unique as it was initially detected in the course of a dental examination.
      Awareness of this lesion is important because inverted schneiderian papilloma and
      adenocarcinoma may be included in the histopathological differential diagnosis.
      Conservative surgical removal is curative and recurrence has not been reported.

PMID- 15153875
TI  - Assessment of p63 expression in the salivary gland neoplasms adenoid cystic
      carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular
      adenomas.
AB  - PURPOSE: The purpose of this study was to determine the extent of p63
      immunoreactivity in the malignant salivary gland neoplasms adenoid cystic
      carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare
      this to the expression of this marker in the benign salivary gland tumors
      canalicular adenoma and basal cell adenoma. Few studies on the expression of p63
      in head and neck salivary gland tumors have been published to date. P63, a
      selective immunohistochemical marker of basal/stem cells of stratified epithelium
      and of myoepithelial cells, is a p53 homologue that plays an essential role in
      both morphogenesis of epidermis and limb development. P63 immunoreactivity has
      been demonstrated in squamous cell and urothelial carcinomas. It is generally
      absent in most nonsquamous cell carcinomas. Study design Formalin-fixed paraffin
      embedded sections from 49 salivary gland neoplasms, representing 6 canalicular
      adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to
      2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde
      Park, NY, were stained with an anti-p63 monoclonal antibody. RESULTS: Nuclear p63
      reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was
      also identified in the majority of cases of ACC (13/15, 87%), primarily in the
      nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular
      adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of
      parotid origin stained strongly for p63, with staining localized to the
      peripheral tumor cells situated adjacent to the connective tissue stroma. None of
      the basal cell adenomas originating in the upper lip stained with p63. In native
      adjacent salivary gland tissue, p63 reactivity was identified focally in the
      nuclei of myoepithelial and basal duct cells. CONCLUSIONS: P63 is strongly
      expressed in basal cell adenoma of parotid origin, and in ACC and PLGA.
      Canalicular adenoma did not demonstrate p63 staining, consistent with this
      tumor's putative luminal ductal cell differentiation. Our results suggest that
      the neoplastic cells in PLGA may represent either a population of p63-positive
      epithelial stem/reserve cells similar to the basal cells of stratified
      epithelium, or modified myoepithelial cells. Given the staining pattern of the
      tumors examined, p63 does not appear to be an ideal marker for distinguishing
      between ACC, PLGA, and basal cell adenoma.

PMID- 15153876
TI  - Case report: Myxoma of the temporalis muscle.
AB  - Intramuscular myxomas of the head and neck are rare entities. Primarily found in
      the myocardium, these lesions also affect the bones and soft tissues. We present
      a case of an intramuscular myxoma of the temporalis muscle. After reviewing the
      literature, this case constitutes, to our knowledge, the second reported
      occurrence of a myxoma in this specific location. The patient was treated for
      this condition with an excisional biopsy after fine needle aspiration revealed a
      benign process. No recurrence was seen 18 months after the excision.

PMID- 15153877
TI  - Successful inferior alveolar nerve decompression for dysesthesia following
      endodontic treatment: report of 4 cases treated by mandibular sagittal osteotomy.
AB  - Endodontic overfilling involving the mandibular canal may cause an injury of the
      inferior alveolar nerve (IAN) resulting in disabling sensory disturbances such as
      pain, dysesthesia, paresthesia, hypoesthesia, or anesthesia. Two fundamental
      mechanisms are responsible for the injury: the chemical neurotoxicity and the
      mechanical compression caused by the extruded material. Although spontaneous
      resorption has been described for some materials, early surgical exploration with
      removal of the material and decompression of the IAN should be performed,
      irrespective of the material used, given that the importance of nerve damage
      increases with the duration of the injury. We report 4 cases of disabling
      dysesthesia and paresthesia following endodontic treatment of lower molars in
      which sagittal osteotomy was used to remove the endodontic paste and to perform
      nerve decompression. All the patients experienced immediate relief of dysesthesia
      and paresthesia.

PMID- 15153878
TI  - Fungi in endodontic infections.
AB  - Fungi are chemoorganotroph eukaryotic microorganisms that can take part in
      endodontic infections and thereby may participate in the etiology of
      periradicular diseases. They possess virulence attributes--including adaptability
      to a variety of environmental conditions, adhesion to a variety of surfaces, the
      production of hydrolytic enzymes, morphologic transition, biofilm formation, and
      evasion and immunomodulation of the host defense--that may play a role in the
      pathogenesis of periradicular diseases. Fungi have occasionally been found in
      primary root canal infections, but they seem to occur more often in the root
      canals of obturated teeth in which treatment has failed. Candida albicans is by
      far the fungal species most commonly isolated from infected root canals, and this
      species has been considered a dentinophilic microorganism because of its invasive
      affinity to dentin. C albicans has also been discovered to be resistant to some
      intracanal medicaments, such as calcium hydroxide. Its ability to invade dentinal
      tubules and resistance to commonly used intracanal medicaments may help to
      explain why C albicans has been associated with cases of persistent root canal
      infections. Some medicaments, such as chlorhexidine digluconate, calcium
      hydroxide combinations (with camphorated paramonochlorophenol or chlorhexidine),
      and EDTA, have the potential to be used as effective intracanal medications for
      patients in whom fungal infection is suspected.

PMID- 15153879
TI  - Patient characteristics associated with receipt of dental radiographic procedures
      during a 48-month population-based study of dentate adults.
AB  - OBJECTIVE: The objective was to test hypotheses that patient characteristics are
      associated with receipt of specific types of radiographic procedures. STUDY
      DESIGN: The Florida Dental Care Study was a prospective cohort study of dentate
      adults. RESULTS: From 19% to 59% of participants received a full-mouth series,
      panoramic, bitewing, or periapical radiograph(s), depending on procedure type.
      Receipt varied with reason(s) for dental visit(s), baseline clinical condition,
      race, approach to care (problem-oriented or regular dental attender), and
      socioeconomic status. CONCLUSION: These findings underscore the distinction
      between what dentists hypothetically would prescribe, compared to what is
      actually received, receipt that results from the interaction between dentist
      recommendations and what patients will accept and pay for. Blacks and lower
      income persons received dental radiograph types that were consistent with less
      comprehensive dental treatment, even with entry into the dental care system,
      reason(s) for incident dental visit(s), baseline clinical status, and regular
      versus problem-oriented attendance taken into account.

PMID- 15153880
TI  - Clinical and magnetic resonance imaging evaluation of facial pain.
AB  - The aim of the study was to evaluate facial pain clinically and to determine the
      frequency with which structural lesions were diagnosed by means of magnetic
      resonance imaging in a sample of patients with facial pain, including refractory
      trigeminal neuralgia and atypical facial pain. Fifty-two patients with facial
      pain were examined clinically, and treatment protocols were adopted for
      trigeminal neuralgia and atypical facial pain. The patients with atypical
      symptoms and those who did not to respond to the treatment underwent magnetic
      resonance imaging to screen for intracranial lesions. Magnetic resonance images
      of 38 patients were obtained. The female-to-male ratio of the patient population
      was 32:20. The mean age of the patients was 57.15 +/- 11.49 years. Intracranial
      lesions were diagnosed in 24 patients. Ten patients had no intracranial pathoses
      visible on magnetic resonance images. Four patients had other pathoses that were
      not related to the facial pain. The most frequently observed extracranial
      pathologic change was sinusitis. It may not be possible to reliably identify high
      risk patients for selective magnetic resonance imaging on the basis of a clinical
      evaluation alone. Routine magnetic resonance imaging for all patients with facial
      pain is recommended to exclude intracranial lesions.

PMID- 15153881
TI  - Arthropods in dermatology.
AB  - Arthropods are important in medicine for a multitude of reasons. Their bites and
      stings may induce allergic reactions, ranging from annoying to life-threatening.
      Many arthropod products are also capable of inciting allergic responses in
      sensitized persons. In recent years, bites and stings have gained greater
      attention owing to increased concern about disease transmission. A common
      hypersensitivity response to arthropod bites, stings, and products is papular
      urticaria. This eruption occurs primarily in children, who eventually "outgrow"
      this disease, probably through desensitization after multiple arthropod
      exposures. Papular urticaria is most often caused by fleas or bedbugs, but
      virtually any arthropod is capable of inducing such a reaction. Two arthropod
      classes of medical importance are the Arachnida (spiders, scorpions, ticks, and
      mites) and the Insecta (lice, fleas, bedbugs, flies, bees, and ants). Animals in
      these two classes are probably responsible for more morbidity and mortality
      worldwide than are any other group of venomous creatures. In general, the
      diagnosis of arthropod bites and stings is dependent on maintenance of a high
      index of suspicion and familiarity with the arthropod fauna not only in one's
      region of practice, but also in the travel regions of one's patients. Learning
      objective At the completion of this learning activity, participants should be
      familiar with the clinical manifestations caused by a variety of arthropods as
      well as the treatment and possible sequelae of arthropod attacks.

PMID- 15153882
TI  - Microbiologic evaluation of skin wounds: alarming trend toward antibiotic
      resistance in an inpatient dermatology service during a 10-year period.
AB  - BACKGROUND: Increasing resistance to commonly used antibiotics has been seen for
      patients with superficial skin wounds and leg ulcers. OBJECTIVES: We sought to
      evaluate bacterial isolates from leg ulcers and superficial wounds for resistance
      to commonly used antibiotics and to compare current data with previous data.
      METHODS: We performed a chart review for patients admitted to a tertiary care
      dermatology inpatient unit from January to December 2001. Comparison was made
      with 2 previous surveys of the same inpatient service from 1992 and 1996.
      RESULTS: Bacterial isolates were cultured from 148 patients, 84% (72 of 86) with
      leg ulcers and 38% (76 of 202) with superficial wounds. Staphylococcus aureus and
      Pseudomonas aeruginosa were the most common bacterial isolates in both groups.
      For patients with leg ulcers, S aureus grew in 67% of isolates (48/72) of which
      75% (36/48) were methicillin-resistant (MRSA). Of leg ulcers, 35% (25/72) grew P
      aeruginosa, which was resistant to quinolones in 56% of cultures (14/25). For
      patients with superficial wounds, S aureus was isolated in 75% (57/76) and 44%
      were MRSA (25/57). P aeruginosa grew in 17% of isolates (13/76) and was resistant
      to quinolones in 18%. We found a marked increase in antibiotic resistance for
      both leg ulcers and superficial wounds. Over time, MRSA increased in leg ulcers
      from 26% in 1992 to 75% in 2001. For superficial wounds, MRSA increased from 7%
      in 1992 to 44% in 2001. P aeruginosa resistance to quinolones in leg ulcers
      increased from 19% in 1992 to 56% in 2001, whereas for superficial wounds there
      was no resistance in 1992 and 18% resistance in 2001. CONCLUSION: Rapid emergence
      of antibiotic-resistant bacteria continues and is a problem of increasing
      significance in dermatology. Common pathogenic bacteria, S aureus and P
      aeruginosa, showed increased resistance to commonly used antibiotics. Selection
      of antibiotics should be on the basis of local surveillance programs.

PMID- 15153883
TI  - Keloids demonstrate high-level epidermal expression of vascular endothelial
      growth factor.
AB  - BACKGROUND: Keloids are a major cause of morbidity, and arise after operation,
      injury, or cutaneous infection. Clinically, keloids differ from hypertrophic
      scars in that they grow beyond the original borders of the injury. Keloids occur
      most commonly for patients of African and Asian descent, and treatment options
      are multiple, indicating that there is no entirely satisfactory treatment for
      keloids. Angiogenesis inhibition has been shown to be effective in treatment of
      malignancy in both animal models and human beings. OBJECTIVE: We sought to
      determine whether keloids produce the potent angiogenic factor vascular
      endothelial growth factor (VEGF). METHODS: We performed in situ hybridization for
      VEGF on keloid tissue and normal skin. RESULTS: Our study demonstrated abundant
      production of VEGF in keloids and, surprisingly, the major source of VEGF was the
      overlying epidermis. CONCLUSIONS: Our results suggest that the overlying
      epidermis is the major source of keloid angiogenesis. These findings demonstrate
      that keloids are angiogenic lesions. Topical antiangiogenic therapy, directed at
      either down-regulating epidermal VEGF or inhibiting keratinocyte-derived VEGF
      activity on its endothelial receptors, may be useful in the treatment of keloids.

PMID- 15153884
TI  - Community-acquired methicillin-resistant Staphylococcus aureus skin infection: a
      retrospective analysis of clinical presentation and treatment of a local
      outbreak.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), a well-known
      nosocomial pathogen, is now emerging as a prominent cause of community acquired
      infections. We have noted an increase in number of cutaneous infections in Los
      Angeles over the past 2 years. The objective of the current study is to evaluate
      the clinical presentation and treatment of community acquired MRSA skin
      infections. METHODS: A retrospective chart review of 39 patients with 46 involved
      sites was performed. The sites of infection, morphology, antimicrobial
      susceptibility, and definitive treatment were evaluated. RESULTS: Cutaneous
      abscesses were the most common presentation of cutaneous MRSA infection.
      Definitive treatment consisted of incision and drainage in combination with
      antimicrobial therapy. The most effective antibiotics were vancomycin,
      trimethoprim/sulfamethoxazole in combination with rifampin, and linezolid.
      CONCLUSION: Community acquired MRSA infection appears to be a growing problem
      requiring prompt diagnosis and treatment. First line treatment is incision and
      drainage in combination with linezolid, vancomycin, or combination
      trimethoprim/sulfamethoxazole and rifampin.

PMID- 15153885
TI  - A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a
      clinically significant endpoint in the assessment of psoriasis.
AB  - A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75)
      is the current benchmark of primary endpoints for most clinical trials of
      psoriasis. Many consider this endpoint to be too stringent as it places
      potentially useful therapies at risk of failing to demonstrate efficacy. We
      hypothesized that a 50% reduction in the PASI score (PASI 50) represents a
      meaningful change in a person's life and thus is a better primary endpoint. To
      test this hypothesis, we analyzed PASI scores, quality of life (QoL) data, and
      desired re-treatment scores from a number of clinical trials in addition to
      studying individual elements that make up the PASI. This analysis shows (1). the
      PASI score is not linearly reflective of psoriasis severity (eg, a reduction in
      area of 95% without a change in redness, scaliness, and induration translates to
      only a 66% reduction in PASI); conversely, a drop in erythema, scale, and
      induration from an average of 3 to 1 would not lead to a 75% reduction in PASI;
      (2). treatment with methotrexate, an effective psoriasis therapy, more frequently
      reaches PASI 50 than PASI 75 as evidenced by a recent open trial in which 63% of
      patients achieved PASI 50 versus 26% achieving PASI 75; (3). improvement in QoL
      exists at PASI 50, using the Dermatology Quality of Life Index, as documented in
      several recently completed large clinical trials; (4). patients achieving PASI 75
      frequently defer therapy until they are well below PASI 50; a clinical trial
      where retreatment was patient initiated showed patients did not re-treat until
      their PASI dropped to an average of 20% improvement from baseline; and (5).
      effective, meaningful therapies are consistently differentiated from placebo at
      PASI 50 as evidenced by histologic and photographic parameters of clinical trials
      of alefacept, efalizumab, and etanercept. We conclude that PASI 50 equates to a
      clinically meaningful improvement in psoriasis and represents a discerning
      primary endpoint.

PMID- 15153886
TI  - Cutaneous angiosarcoma: a case series with prognostic correlation.
AB  - BACKGROUND: Cutaneous angiosarcoma (CA) is a rare and aggressive endothelial
      derived sarcoma. Few large studies have examined the clinicopathologic and
      prognostic attributes of CA. OBJECTIVES: We sought to discern the potential
      prognostic significance of a variety of demographic features (i.e., age, sex,
      location), histologic attributes (i.e., depth of invasion, tumor necrosis, tumor
      cell morphology, margin status, mitoses), and follow-up data (i.e., tumor
      recurrence, metastases) in CA. METHODS: The statistical influence of age, sex,
      anatomic location, tumor depth of invasion, tumor cell morphology, presence or
      absence of necrosis, number of mitoses, and margin status on time to tumor
      recurrence and metastases were examined in a series of 47 patients with CA.
      Angiosarcoma arising within the breast, in a previously irradiated anatomic site,
      and a pre-existing vascular malformation or one associated with a lymphedematous
      extremity were excluded from study. RESULTS: Most of the patients were men (76%),
      with an average age of 75.1 years (range: 59-92 years). The most common location
      was the head and neck region (96%). The most common presentation was of a rapidly
      expanding erythematous patch, and the most common clinical impression was
      angiosarcoma. The average external diameter of the tumor was 5.3 cm (range: 1.1
      8.9 cm). The most common histologic pattern was characterized by anastomosing
      dissecting sinusoids lined by atypical endothelial cells (64%) with 15% of cases
      showing a diffuse epithelioid or spindle cell proliferation and 21% showing a
      mixture of the 2 histologic patterns. The average depth of tumor invasion was
      2.86 mm (range: 1.8->6.0 mm). Of the tumors, 78% had a mitotic rate that exceeded
      3/mm(2). Follow-up was available in 37 of the patients and ranged from 6 to 65
      months. The 5-year local recurrence rate was 84% and the overall 5-year survival
      was 34%. Most patients died as a result of their disease with widespread
      pulmonary, cardiac, and/or brain metastases. CONCLUSIONS: Of the gross and
      histologic features, external diameter (>5 cm), depth of invasion (>3 mm),
      mitotic rate (>3 HPF), positive surgical margins, tumor recurrence, and
      metastases correlated with adverse outcome by univariate analysis and, with the
      exception of mitotic rate, by multivariate analysis. Of the foregoing, tumor
      diameter, depth of invasion, positive margins, metastases, and tumor recurrence
      were the most robust predictors of outcome. None of the demographic factors was
      associated with outcome. This study confirms the poor prognosis of patients with
      CA. Among all demographic and histologic patterns examined for prognostic
      significance, tumor diameter, tumor depth of invasion, margin status, tumor
      recurrence, and metastases emerged as the most important determinants of outcome.

PMID- 15153887
TI  - Congenital hemangiomas and infantile hemangioma: missing links.
AB  - Rapid postnatal growth and slow involution in childhood characterize the common
      infantile hemangioma. There are other rare vascular tumors that present fully
      grown at birth and behave quite differently, as designated by the acronyms:
      rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital
      hemangioma (NICH). RICH and NICH have similarities in appearance, location, size,
      equal sex ratio, and both have overlapping radiologic and histologic features
      with infantile hemangioma. However, neither type of congenital tumor immunostains
      for glucose transporter-1 protein, a marker of infantile hemangioma. This raises
      the question of whether these congenital vascular lesions are variations in a
      spectrum of hemangioma or are entirely different tumors. We describe two groups
      of patients that suggest a linkage between postnatal and congenital vascular
      tumors: Link I (n=5), children who had either RICH or NICH coexisting with
      infantile hemangioma, and Link II (n=10), children initially diagnosed as having
      RICH, but regression was incomplete and the residuum was that of NICH. We
      conclude that these infants exhibit "missing links" between the rare RICH and
      NICH, and the common infantile hemangioma.

PMID- 15153888
TI  - The effect of two skin cleansing systems on moderate xerotic eczema.
AB  - BACKGROUND: Moderate xerotic eczema, characterized by stratum corneum
      desquamation, erythema, and pruritus is a common condition that can be induced or
      worsened by skin cleansing. Traditional dermatologic therapy includes the use of
      emollients, medium or high potency topical corticosteroids, and a change in
      bathing habits. OBJECTIVE: To investigate the effect of two cleansing systems: a
      synthetic detergent bar soap applied with a cotton washcloth and a petrolatum
      delivering body wash applied with a polyethylene puff as part of a topical
      treatment approach to moderate xerotic eczema. METHOD: Sixty patients with
      moderate xerotic eczema were enrolled in a 4-week investigator-blinded study.
      Half were randomly treated with a strong topical corticosteroid cream (0.05%
      fluocinonide) and a traditional cleansing system consisting of a synthetic
      detergent bar soap applied with a washcloth. The remaining patients were treated
      with a weaker, medium strength topical corticosteroid cream (0.1% triamcinolone
      acetonide) and a novel cleansing system consisting of a petrolatum-delivering
      body wash applied with a polyethylene puff. Dermatologist investigator
      evaluations and patient self-assessments were conducted at baseline, 2 weeks, and
      4 weeks. RESULTS: Patients using the novel petrolatum-delivering body wash and
      polyethylene puff cleansing system and the lower potency corticosteroid cream
      demonstrated significantly greater clinical improvement than those patients using
      the traditional cleansing system of a synthetic detergent beauty bar and
      washcloth system and the higher potency corticosteroid cream after both 2 and 4
      weeks of treatment. CONCLUSION: The cleansing system of a petrolatum-delivering
      body wash delivered by a polyethylene puff may be useful as a cleanser for
      patients with moderate xerotic eczema.

PMID- 15153889
TI  - Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a
      pilot study.
AB  - Nocturnal pruritus is a significant problem for patients with inflammatory skin
      diseases and many systemic diseases. The oral therapies currently available have
      a limited effect. We present an open, uncontrolled pilot study of 3 patients with
      inflammatory skin diseases and severe nocturnal pruritus who underwent treatment
      with mirtazapine (Remeron), a noradrenergic and specific serotonergic
      antidepressant. Mirtazapine is a safe medication without serious side effects and
      may be an effective alternative for the treatment of nocturnal pruritus.

PMID- 15153890
TI  - Treatment of acquired perforating dermatosis with narrowband ultraviolet B.
AB  - Acquired perforating dermatosis is difficult to treat. We describe effective
      therapy of acquired perforating dermatosis with narrowband UVB in 5 patients.
      Phototherapy was given 2 or 3 times weekly. The dose was started at 400 mJ/cm(2)
      and increased to a maximum of 1500 mJ/cm(2). All lesions disappeared completely
      after 10 to 15 exposures without adverse effects. Two patients with diabetes
      mellitus but without chronic renal failure experienced no recurrence until 5 and
      10 months after stopping the phototherapy. One patient undergoing hemodialysis
      for chronic renal failure experienced a recurrence of pruritus and small papules
      after 1 month. Two patients undergoing hemodialysis showed no recurrence during
      narrowband UVB maintenance therapy until 7 and 8 months.

PMID- 15153891
TI  - Is Degos' disease a clinical and histological end point rather than a specific
      disease?
AB  - Degos' disease is described as a rare disorder, with approximately 100 cases
      detailed in the literature. Nearly all are characterized by the near
      "pathognomonic" appearance of porcelain-white, atrophic papules with peripheral
      erythema and telangiectases. Many Degos' disease variants have been described
      including benign cutaneous Degos' disease, familial Degos' disease, atrophie
      blanche with Degos'-like features, and connective tissue diseases with similar
      findings. The course, prognosis, and treatment have substantially varied. We
      present four patients: the first carries a diagnosis compatible with classic
      Degos' disease, the second and third demonstrate cutaneous and histological
      findings of Degos' disease but laboratory evidence suggestive of lupus
      erythematosus, while the fourth has dermatomyositis with Degos'-like lesions.
      Because of broad overlap in clinical and histological findings, we contend that
      Degos' disease may not be a specific entity, but rather, may represent a common
      end point to a variety of vascular insults, many of which have not been fully
      elucidated.

PMID- 15153892
TI  - American Academy of Dermatology Consensus Conference on the safe and optimal use
      of isotretinoin: summary and recommendations.

PMID- 15153893
TI  - Standard grading system for rosacea: report of the National Rosacea Society
      Expert Committee on the classification and staging of rosacea.

PMID- 15153894
TI  - Challenges facing Chinese health care.

PMID- 15153895
TI  - Paleodermatoses: lessons learned from mummies.
AB  - Mummies, the preserved remains of living beings from former times, bear witness
      across millennia to the maladies plaguing humankind. Disease, older than
      humanity, is better understood when examined in the context of history.
      Paleopathology, literally meaning "ancient suffering", is the study of disease
      through evaluation of ancient remains. This area of increasing medical interest
      offers insights into the management of public health issues and disease
      epidemiology. This article provides an introduction and overview to
      paleodermatology, the branch of dermatology concerned with the evaluation of
      diseases associated with the integument by examination of ancient human remains.
      Mummy sources, how they were made and used throughout history, and the
      multidisciplinary approach used to study skin diseases found in mummies is
      briefly described. Despite pervasive pseudopathology, a remarkable array of
      diseases are well substantiated in the paleorecord, including infectious,
      heritable, nutritional, hormonal, acquired, iatrogenic, and neoplastic disorders.
      Legitimate ethical concerns have been raised in the use of human remains for any
      purpose, with the lack of informed consent eliciting accusations of exploitation.
      While these studies are undertaken with certain risks, such as the acquisition of
      potentially dangerous or extinct infections, paleodermatology offers a unique and
      historical perspective on the afflictions of the skin and the way of all flesh.

PMID- 15153896
TI  - Hyperandrogenism and the skin.

PMID- 15153897
TI  - Surgical pearl: nail edge separation with dental floss for ingrown toenails.

PMID- 15153898
TI  - Topical 5-fluorouracil is ineffective in the treatment of extensive alopecia
      areata.
AB  - We report the results of a pilot study of topical 5% 5-fluorouracil (FU) cream
      for the treatment of alopecia areata, an immunologically modulated disorder of
      hair growth. Patients with extensive (>50% scalp surface area involvement)
      alopecia areata that was refractory to previous treatments applied 5-FU to one
      side of their scalp twice daily for 3 to 6 months. In all, 9 patients enrolled,
      and 8 completed the study. No patient experienced measurable hair growth on the
      treated side. Only mild irritation was observed in a subset of patients with
      application of 5-FU to the nonphotodamaged scalp skin. Based on these results, we
      cannot recommend the use of topical 5-FU for treatment of alopecia areata without
      further evidence of therapeutic benefit.

PMID- 15153899
TI  - Monochromatic excimer light (308 nm) in patch-stage IA mycosis fungoides.
AB  - Recently, numerous studies have been reported concerning the treatment of early
      stage mycosis fungoides (MF) with narrowband (311-nm) UVB, claiming a beneficial
      response. We have used for the first time a 308-nm monochromatic excimer light, a
      new kind of xenon-chloride lamp, in the treatment of patch stage IA MF. We
      treated 7 patch lesions in 4 patients with unequivocal clinicopathologic
      diagnosis of MF. All lesions achieved clinical and histologic complete remission.
      The number of weekly sessions varied from 4 to 11 (mean 6.5; median 5.5). The
      total UVB 308-nm irradiation dose ranged from 5 to 9.3 J/cm(2) (mean 7.1 J/cm(2);
      median 7 J/cm(2)). All lesions remained in stable complete remission after a
      follow-up of 3 to 28 months. No remarkable side effects were reported. Our
      preliminary results suggest that monochromatic excimer light phototherapy is a
      possibly very useful treatment modality in patch stage IA MF.

PMID- 15153900
TI  - Treatment of extensive chronic cutaneous graft-versus-host disease in an infant
      with topical pimecrolimus.
AB  - We report a case of generalized cutaneous chronic graft-versus-host disease in a
      17-month-old infant. Topical treatment with the novel ascomycin substance
      pimecrolimus once daily for 4 weeks led to a near complete clearance of skin
      lesions. Importantly, this excellent clinical response was obtained without
      additional use of systemic immunosuppressive treatment.

PMID- 15153901
TI  - The trigeminal trophic syndrome: an unusual cause of nasal ulceration.
AB  - Trigeminal trophic syndrome (TTS) is an unusual complication after peripheral or
      central damage to the trigeminal nerve, characterized by anesthesia,
      paresthesias, and ala nasi ulceration. We describe a patient with classic TTS
      after trigeminal rhizotomy who underwent several extensive evaluations for nasal
      ulceration and received prolonged immunosuppressive therapy for a presumed
      autoimmune disorder before the correct diagnosis was made. An understanding of
      the predisposing factors and clinical presentation of TTS is important to ensure
      a timely diagnosis of this difficult-to-treat illness. Differentiation of TTS
      from malignancy, infection, or vasculitis is possible on the basis of clinical
      history, tissue biopsy, and serologic evaluation.

PMID- 15153902
TI  - Cutaneous drug eruption from cetirizine and hydroxyzine.
AB  - Topical application of the antihistamines commonly leads to sensitization for
      patients, but skin reactions provoked by their systemic use are very rare. The
      antihistamines cetirizine and hydroxyzine are piperazine derivatives, on the
      structural basis of an ethylenediamine, but the cross-reactions between the 2
      have rarely been reported. A 44-year-old man visited because of the generalized
      morbilliform eruptions with pruritus over his whole body, after intake of
      hydroxyzine (Ucerax) and azelastine (Azeptine), administered during a 2-day
      period for chronic urticaria. Previously, he had presented the same cutaneous
      reactions after oral administration of cetirizine (Lotec). Oral challenge tests
      performed with cetirizine and hydroxyzine led to the same cutaneous reactions. He
      was given the diagnosis of drug eruption from cetirizine and hydroxyzine, which
      suggests that there were cross-reactions among cetirizine, hydroxyzine, and
      ethylenediamine.

PMID- 15153903
TI  - The epidermal nevus syndromes: multisystem disorders.
AB  - The epidermal nevus syndromes are a group of congenital syndromes comprising
      epidermal nevi in conjunction with central nervous system (CNS), ocular,
      musculoskeletal, and other organ anomalies. We describe a patient with epidermal
      nevi and multiple organ abnormalities, highlighting the wide spectrum of
      involvement in epidermal nevus syndromes, and briefly summarize the literature on
      these rare syndromes.

PMID- 15153904
TI  - Allergic contact dermatitis from tacrolimus.
AB  - A 9-year-old boy developed allergic contact dermatitis from tacrolimus ointment.
      Tacrolimus was proven to be the allergen by right-versus-left double-blinded
      provocative use testing of tacrolimus ointment 0.1% versus inactive vehicle
      applied twice daily to normal preauricular and antecubital skin. Facial
      dermatitis appeared after 1 week and antecubital dermatitis after 7 weeks.
      Furthermore, patch testing of each individual ingredient was positive only with
      tacrolimus; a concentration of 2.5% in ethanol was required. Forty control
      patients had negative patch tests with tacrolimus 5% in ethanol. We hypothesize
      that the unusually long time required to elicit a positive use test on the arm
      and the high patch test concentration required on the back are caused by low
      percutaneous absorption through normal extrafacial skin. This is likely to be
      caused in part by the high molecular weight of tacrolimus. A similar phenomenon
      may occur when patch testing with neomycin sulfate.

PMID- 15153905
TI  - Complete remission of Merkel cell carcinoma of the scalp with local and regional
      metastases after topical treatment with dinitrochlorbenzol.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive tumor with a high percentage
      of recurrence, metastatic spread, and mortality. Treatment of metastasized MCC is
      not standardized and prognosis of metastasized MCC is often poor. Current
      protocols recommend surgery, adjuvant radiation therapy, and often lymph node
      dissection to prevent recurrences. A few sporadic reports of spontaneous
      regression of MCC suggest a so far not yet characterized role and potential of
      the immune system in controlling this tumor. We describe a 69-year-old man with
      extended inoperable MCC of the scalp including multiple local and regional
      metastases who responded with complete remission to 4 weekly treatments of
      topically applied immune-modulating dinitrochlorbenzol. Together with subsequent
      irradiation, remission has now lasted for more than 1 year.

PMID- 15153906
TI  - An unusual combination: lipedema with myiasis.
AB  - Lipedema refers to the abnormal deposition of subcutaneous fat causing a striking
      enlargement of the lower extremities that is out of proportion to the upper body.
      Most clinicians are unaware of this disease and thus it is seldom diagnosed
      correctly. Cutaneous myiasis is the infestation of skin by fly larvae. We
      describe an unusual case of a woman with lipedema who developed cutaneous
      myiasis.

PMID- 15153907
TI  - Erythema ab igne induced by a laptop computer.

PMID- 15153908
TI  - Long-term complete remission of severe pemphigus vulgaris with monoclonal anti
      CD20 antibody therapy and immunophenotype correlations.

PMID- 15153909
TI  - Concurrent development of eruptive xanthogranulomas and hematologic malignancy:
      two case reports.

PMID- 15153910
TI  - Cutaneous sarcoidosis treated with medium-dose UVA1.

PMID- 15153911
TI  - Is superficial morphea synonymous with atrophoderma Pasini-Pierini?

PMID- 15153912
TI  - Treatment of anal intraepithelial neoplasia in patients with acquired HIV with
      imiquimod 5% cream.

PMID- 15153913
TI  - Treatment of recalcitrant lower extremity ulcers with topical becaplermin.

PMID- 15153914
TI  - Lack of the effect of topical vitamin K on bruising after mechanical injury.

PMID- 15153916
TI  - Supernumerary nipple and cardiocutaneous associations.

PMID- 15153917
TI  - Liver biopsy in patients without psoriasis receiving methotrexate: what
      guidelines are medical dermatologists following?

PMID- 15153919
TI  - The lack of a clinical effect of cimetidine in the treatment of epidermodysplasia
      verruciformis.

PMID- 15153918
TI  - Treatment of cutaneous leishmaniasis by photodynamic therapy.

PMID- 15153920
TI  - Staging classification of blood involvement in cutaneous T-cell lymphoma.

PMID- 15153921
TI  - APIC position paper: Improving health care worker influenza immunization rates.
AB  - The Association for Professionals in Infection Control and Epidemiology (APIC) is
      a non-profit, international organization governed and directed by a board of
      directors, consisting of four officers and 10 directors. APIC has more than 110
      regional Chapters in the United States and more than 10,000 members worldwide. As
      an authority in infection control, APIC endorses the Advisory Committee on
      Immunization Practices' (ACIP) recommendations published by the Centers for
      Disease Control and Prevention (CDC) in Morbidity and Mortality Weekly Reports

PMID- 15153922
TI  - Frequency of vaccinia virus isolation on semipermeable versus nonocclusive
      dressings covering smallpox vaccination sites in hospital personnel.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends a
      semipermeable occlusive dressing for hospital workers who receive smallpox
      vaccination. OBJECTIVE: The study was designed to determine the frequency of
      vaccinia virus isolation from the outer surface of semipermeable dressings and to
      compare the prevalence of vaccinia virus on the outer surface of semipermeable
      dressings with its prevalence on the outer surface of nonocclusive dressings.
      METHODS: A prospective, observational study was conducted on hospital employees
      who received smallpox vaccination at a military academic medical center. Subjects
      were instructed to wear a semipermeable dressing if they had direct patient
      contact. Employees without direct patient care had the option of wearing a
      semipermeable dressing or a nonocclusive dressing. Prior to a programmed dressing
      change, the outer surface of the bandage site was swabbed and cultured for virus.
      Samples were considered positive when cytopathic effects were observed, with
      results confirmed as vaccinia by polymerase chain reaction. RESULTS: A total of
      212 cultures were obtained from 93 subjects. All cultures directly obtained from
      active lesions were positive (13/13). Positive cultures were obtained from 7%
      (10/135) of the semipermeable dressings and 23% (15/64) of the nonocclusive
      dressings (P <.05). Ten percent (8/79) of the semipermeable dressings with
      purulent exudate observed underneath the bandage were culture positive, compared
      with 4% (2/56) of semipermeable dressings with no purulent exudate observed
      underneath the bandage (P=.19). CONCLUSIONS: Compared with nonocclusive
      dressings, the semipermeable dressing reduced, but did not eliminate, the
      frequency with which vaccinia virus was cultured from the surface of the
      dressing. Virus was present, but only rarely, on the dressing surface in the
      absence of purulent exudate under the semipermeable dressings.

PMID- 15153923
TI  - Prospective surveillance study for risk factors of central venous catheter
      related bloodstream infections.
AB  - OBJECTIVE: Risk factors of catheter-related bloodstream infection (CR-BSI) caused
      by central venous catheter (CVC) use at a university hospital were evaluated.
      DESIGN: A prospective, observational, hospital-wide study was conducted. SETTING:
      The study was conducted at a university hospital with 1050 beds. METHODS:
      Nontunneled catheters were used, and double or triple lumen was observed.
      Catheters were cultured by semi-quantitative method, and blood cultures were
      performed if necessary. All epidemiologic and clinical data were recorded without
      intervention during the study. RESULTS: Over a 1-year period, the study assessed
      389 CVCs inserted in 367 patients (mean age 50.9 +/- 18.1 years; 215 [58.6%] men,
      152 [41.4%] women). Duration of catheterization was 12.0 +/- 9.9 days. CVCs were
      inserted into either the subclavian vein (N=263; 67.6%) or the jugular vein
      (N=128; 32.4%). In 250 episodes (64.3%), antibiotics were used concomitantly. CR
      BSI was found in 43 of all CVCs (11.1%). The rate of CR-BSI per 1000 catheter
      days was 9.21 for the whole cohort. In multivariable analysis, only renal failure
      (OR 4.83; CI 1.32-17.66; P=.017) was found to be a risk factor for CR-BSI.
      CONCLUSION: Renal failure was an independent risk factor for CR-BSI.

PMID- 15153924
TI  - Prospective study of the impact of open and closed infusion systems on rates of
      central venous catheter-associated bacteremia.
AB  - OBJECTIVE: We sought to ascertain the effect of switching from an open infusion
      system to a closed system on rates and sequelae of central venous catheter (CVC)
      associated bloodstream infection in the intensive care department (ICU) of 2
      hospitals in Argentina. METHODS: A prospective, controlled, time-series, cohort
      trial was undertaken in adult patients admitted to 4 level-III adult ICUs in
      Buenos Aires, Argentina, who had a CVC in place for at least 24 hours. Rates of
      CVC-associated bloodstream infection during a period of active surveillance with
      an open system (baseline; externally vented, semirigid, noncollapsible, 1-port
      plastic bottles) were compared with rates after switching to a closed system
      (intervention; nonvented, collapsible, 2-port plastic bags). RESULTS: Between
      August 1999 and March 2002, 992 patients in the ICU with CVCs were enrolled.
      Patients during each study period (open system, 608; closed system, 384) were
      similar with respect to sex, severity-of-illness score, and prevalence of
      diabetes and cancer. Compliance with handwashing and CVC site care was also
      similar during the 2 study periods. The incidence of CVC-associated bacteremia
      during use of the closed system was significantly lower than during use of the
      open system (2.36 vs 6.52/1000 catheter-days, relative risk=0.36, 95% confidence
      interval=0.14-0.94, P=.02); bacteremias caused by gram-negative bacilli declined
      by 64%. In all, 17 patients with catheter-associated bacteremia died during the
      period when the open system was in use (2.8%), versus only 1 (0.2%) during use of
      the closed system (relative risk 0.09, P=.003). The calculated cost savings in
      the 20 hospital-month intervention period was $53,768 and 130.9 ICU days.
      CONCLUSION: Adoption of a closed infusion system resulted in major reductions in
      the incidence of catheter-associated bacteremia, related mortality, and cost.
      Because most Latin American hospitals still use externally vented fluid
      containers, switching to nonvented bags could substantially reduce rates of
      nosocomial bacteremia.

PMID- 15153925
TI  - Using maximal sterile barriers to prevent central venous catheter-related
      infection: a systematic evidence-based review.
AB  - BACKGROUND: Catheter-related infections cause increased morbidity, mortality, and
      health care costs. Infection control experts advocate using maximal sterile
      barriers to reduce the incidence of these infections. Low compliance rates
      suggest that clinicians are not convinced or are not aware that available data
      support adopting this more cumbersome, time-consuming, and relatively more
      expensive technique. Accordingly, we conducted a systematic, evidence-based
      review of the medical literature to determine the value of maximal sterile
      barriers. DATA SOURCES: We used multiple computerized databases, reference lists
      of identified articles, and queries of prominent investigators. STUDY SELECTION:
      We selected studies comparing infectious outcomes using maximal sterile barriers
      versus using less stringent sterile barrier techniques during central venous
      catheter insertion. DATA SYNTHESIS: We found only 3 primary research studies.
      Although each study suggests maximal sterile barriers may reduce infectious
      complications, the evidence supporting this conclusion is incomplete. The only
      randomized controlled trial limited enrollment to ambulatory oncology patients.
      These 3 studies differed notably in their patient populations, research designs,
      and health care settings. CONCLUSION: The medical literature suggests maximal
      sterile barriers are advantageous in at least one setting and may be useful in
      others. While we believe the available evidence does support the use of maximal
      sterile barriers during routine insertion of central venous catheters,
      prospective studies and economic analyses would better clarify its value.

PMID- 15153926
TI  - Monitoring and educational feedback to improve the compliance of tattooists and
      body piercers with infection control standards: a randomized controlled trial.
AB  - OBJECTIVES: Blood-borne viruses, which present a grim health and economic burden
      for both developed and developing countries, can be transmitted through tattooing
      and piercing. Limited data exist concerning intervention strategies for
      increasing skin penetration operators' compliance with infection control
      standards. We evaluated the efficacy and acceptability of an educational feedback
      intervention for tattooists and piercers. METHODS: A randomized controlled trial
      was conducted in Sydney, NSW, Australia, among 37 tattooing and body-piercing
      premises in 2002. RESULTS: No effects were found in terms of improved knowledge.
      There was a significantly greater increase in the experimental group in the
      perceived risk of being detected and penalized for noncompliance. There was a
      significantly greater improvement in the demonstration of 2 of 3 infection
      control procedures and a nonsignificant trend toward greater improvement in
      inspection scores in the experimental group. The odds of compliance were
      significantly higher in the experimental group for 2 of the 3 demonstration
      practices and in 2 of 5 observed infection control practices. CONCLUSION: The
      findings contribute new information concerning alternative approaches to
      increasing tattooists and piercers' infection control compliance with
      regulations/guidelines.

PMID- 15153927
TI  - Incidence of bloodstream infection in multicenter inception cohorts of
      hemodialysis patients.
AB  - OBJECTIVE: To assess incidence of and identify risk factors for bloodstream
      infection in patients starting hemodialysis or starting a new means of vascular
      access for hemodialysis. METHOD: Two cohorts of patients, 1 initiating
      hemodialysis (new patients) and a 1:1 matching group of patients continuing
      hemodialysis but starting a new vascular access (continuing patients), were
      enrolled from 9 Canadian hemodialysis units and followed for 6 months.
      Bloodstream infection was defined using established criteria. A nested case
      control study was carried out, using as cases those cohort patients diagnosed
      with infection. Each case was matched with a control having the same means of
      access and new or continuing status. RESULTS: A total of 527 patients (258 new,
      269 continuing), were recruited and underwent 31,268 hemodialysis procedures
      during this 6-month follow-up. There were 96 bloodstream infections in 93
      patients (11.97/10,000 days, 28.81/10,000 hemodialysis procedures), yielding a
      relative risk of infection of 3.33 (95% CI, 2.12-5.24) for patients with a
      previous bloodstream infection and 1.56 (95% CI, 1.02-2.38) for patients
      continuing hemodialysis by a new means of access. Survival analysis revealed that
      compared to arteriovenous fistula vascular access, the relative risk of
      bloodstream infection in patients was 1.47 (95% CI, 0.36-5.96) for arteriovenous
      grafts, 8.49 (95% CI, 3.03-23.78) for cuffed central venous catheters, and 9.87
      (95% CI, 3.46-28.20) for uncuffed central venous catheters. The regression model
      of the case-control study identified earlier bloodstream infection (OR, 6.58),
      poor patient hygiene (OR, 3.48), and superficial access-site infection (OR, 4.36)
      as additional risk factors. CONCLUSION: During the first 6 months there is a high
      rate of bloodstream infection in patients starting hemodialysis either for the
      first time or by a new means of vascular access. Previous hemodialysis
      bloodstream infection and continuing hemodialysis by a new means of vascular
      access are markers for an increased risk of infection, as is poor patient
      hygiene. Central venous catheter vascular access, whether cuffed or uncuffed, has
      a much higher infection risk. In this study, there was no difference in infection
      rate between cuffed and uncuffed central catheters.

PMID- 15153928
TI  - Survey of oral care practices in US intensive care units.
AB  - BACKGROUND: Research has shown that oral care involving toothbrushes and topical
      antimicrobials improves the oral health of medically compromised patients and may
      reduce the incidence of nosocomial infections including pneumonia. This survey
      research was undertaken to determine the type and frequency of oral care in
      intensive care units (ICUs) in the United States and the attitudes, beliefs, and
      knowledge of health care workers. METHODS: A randomly selected survey of 102 ICUs
      within the continental United States participated with 556 respondents; 97% of
      respondents were registered nurses. MEASUREMENTS: Frequency and type of oral care
      provided, attitudes and beliefs, and knowledge and training in oral care were
      measured. RESULTS: Ninety-two percent of respondents perceived oral care to be a
      high priority. The primary methods of oral care involved the use of foam swabs,
      moisturizers, and mouthwash. Toothbrushes and toothpaste were used infrequently
      by almost 80% of respondents. The majority of nurses indicated a need for
      research-proven oral care standards and desired to learn more. CONCLUSIONS: In
      this random sample of ICUs, oral care methods were not consistent with current
      research and oral care protocols. The translation of oral care research into
      practice in the ICU may improve the quality of care and decrease the incidence of
      ventilator-associated pneumonia.

PMID- 15153929
TI  - Removal of biofilm from endoscopes: evaluation of detergent efficiency.
AB  - BACKGROUND: Biofilm consisting of bacteria enclosed in a matrix of
      exopolysaccharide (EPS) forms on many medical devices such as catheters and
      implants. Nosocomial infection is, thus, a newly recognized scenario of biofilm
      development. Biofilm removal by physical methods such as ultrasound and
      mechanical cleaning is reasonably effective but difficult to supervise in
      practice. Chemical methods are often ineffective because of biofilm resistance to
      biocides. In this study, we compared the efficiency of different detergents used
      in endoscope reprocessing. METHODS: Escherichia coli biofilm was generated on
      Teflon and medical grade PVC tubing under low flow conditions. Sections of
      biofilm covered tubing were washed using test detergents and biofilm removal was
      assessed by counting remaining adherent bacteria after washing and by scanning
      electron microscopy to qualitatively assess the amount and nature of the
      remaining biofilm. RESULTS: Control tubing developed a multilayered biofilm
      consisting of >10(5) bacterial cells/cm(2). Only Matrix (Whiteley Medical,
      Sydney, Australia) produced >4 log reduction in viable bacterial numbers. Matrix
      and Epizyme Rapid (3M Australia, Pymble, Australia) were able to remove up to 75%
      and 60% of the biofilm, respectively. CONCLUSIONS: Many commonly used enzymatic
      cleaners fail to reduce the viable bacterial load or remove the bacterial EPS.
      Cleaners with high enzyme activity, Epizyme Rapid, removed more biofilm but
      failed to reduce bacterial numbers more than 2 logs. The only cleaner containing
      no enzymes, Matrix, significantly reduced bacterial viability and residual
      bacterial EPS.

PMID- 15153931
TI  - The LIFE Trial in 2004.

PMID- 15153930
TI  - Role of biofilm in catheter-associated urinary tract infection.
AB  - The predominant form of life for the majority of microorganisms in any hydrated
      biologic system is a cooperative community termed a "biofilm." A biofilm on an
      indwelling urinary catheter consists of adherent microorganisms, their
      extracellular products, and host components deposited on the catheter. The
      biofilm mode of life conveys a survival advantage to the microorganisms
      associated with it and, thus, biofilm on urinary catheters results in persistent
      infections that are resistant to antimicrobial therapy. Because chronic
      catheterization leads almost inevitably to bacteriuria, routine treatment of
      asymptomatic bacteriuria in persons who are catheterized is not recommended. When
      symptoms of a urinary tract infection develop in a person who is catheterized,
      changing the catheter before collecting urine improves the accuracy of urine
      culture results. Changing the catheter may also improve the response to
      antibiotic therapy by removing the biofilm that probably contains the infecting
      organisms and that can serve as a nidus for reinfection. Currently, no proven
      effective strategies exist for prevention of catheter-associated urinary tract
      infection in persons who are chronically catheterized.

PMID- 15153932
TI  - Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic
      reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2
      treated cells.
AB  - Cholera toxin (CT) follows a glycolipid-dependent entry pathway from the plasma
      membrane through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER)
      where it is retro-translocated into the cytosol to induce toxicity. Whether
      access to the Golgi apparatus is necessary for transport to the ER is not known.
      Exo2 is a small chemical that rapidly blocks anterograde traffic from the ER to
      the Golgi and selectively disrupts the Golgi apparatus but not the TGN. Here we
      use Exo2 to determine the role of the Golgi apparatus in CT trafficking. We find
      that under the condition of complete Golgi ablation by Exo2, CT reaches the TGN
      and moves efficiently into the ER without loss in toxicity. We propose that even
      in the absence of Exo2 the glycolipid pathway that carries the toxin from plasma
      membrane into the ER bypasses the Golgi apparatus entirely.

PMID- 15153933
TI  - Processed caspase-2 can induce mitochondria-mediated apoptosis independently of
      its enzymatic activity.
AB  - The mechanism by which caspase-2 executes apoptosis remains obscure. Recent
      findings indicate that caspase-2 is activated early in response to DNA-damaging
      antineoplastic agents and may be important for the engagement of the
      mitochondrial apoptotic pathway. We demonstrate here that fully processed caspase
      2 stimulates mitochondrial release of cytochrome c and Smac/DIABLO, but not
      apoptosis-inducing factor (AIF). This event occurs independently of several Bcl-2
      family proteins, including Bax, Bak and Bcl-2, and inactivation experiments
      reveal that the proteolytic activity of caspase-2 is not required for the effect.
      Further, functional studies of mitochondria indicate that processed caspase-2
      stimulates state 4 respiration and decreases the respiratory control ratio as a
      result of, in large part, an uncoupling effect. Combined, our data suggest that
      caspase-2 retains a unique ability to engage directly the mitochondrial apoptotic
      pathway, an effect that requires processing of the zymogen but not the associated
      catalytic activity.

PMID- 15153935
TI  - Alpine pathways of membrane traffic.

PMID- 15153934
TI  - Agrobacterium proteins VirD2 and VirE2 mediate precise integration of synthetic T
      DNA complexes in mammalian cells.
AB  - Agrobacterium tumefaciens-mediated plant transformation, a unique example of
      interkingdom gene transfer, has been widely adopted for the generation of
      transgenic plants. In vitro synthesized transferred DNA (T-DNA) complexes
      comprising single-stranded DNA and Agrobacterium virulence proteins VirD2 and
      VirE2, essential for plant transformation, were used to stably transfect HeLa
      cells. Both proteins positively influenced efficiency and precision of transgene
      integration by increasing overall transformation rates and by promoting full
      length single-copy integration events. These findings demonstrate that the
      virulence proteins are sufficient for the integration of a T-DNA into a
      eukaryotic genome in the absence of other bacterial or plant factors. Synthetic T
      DNA complexes are therefore unique protein:DNA delivery vectors with potential
      applications in the field of mammalian transgenesis.

PMID- 15153936
TI  - Transgenic TCR expression: comparison of single chain with full-length receptor
      constructs for T-cell function.
AB  - Genetic modification of T lymphocytes with T-cell receptor (TCR) genes provides a
      novel tool for adoptive immunotherapy. However, the efficiency of full-length TCR
      (flTCR)-transduced T cells could be limited by factors such as incorrect pairing
      between exogenous and endogenous TCR chains and downregulation of the CD3
      complex. To overcome these hurdles, one promising strategy is to use three-domain
      single-chain TCRs (3D-scTCR), in which TCR Valpha and Vbeta chains are joined by
      a linker with signal transduction domains fused at the carboxyl termini as signal
      transducers and amplifiers. Our results showed that surface expression of scTCRs
      on T cells after retroviral transduction was affected by the origin of the
      transmembrane (TM) region and placement of signaling domains. scTCR-modified T
      cells were functional as shown by cytokine (IL-2 and IFN-gamma) release in
      response to antigen stimulation and cytolytic activity against specific target
      cells. CD8 and CD28, but not the complete CD3 complex, could enhance the scTCR
      induced T cell activation. Compared with flTCR-modified T cells and native CTLs,
      scTCR-modified T cells require higher thresholds of antigen stimulation
      (approximately 10(-8) M peptide) to be functional. Despite the low efficiency of
      scTCRs, our data provide insight into further improvements in generating
      efficient scTCRs for in vivo applications.

PMID- 15153937
TI  - Induction of T-cell antitumor immunity and protection against tumor growth by
      secretion of soluble human CD70 molecules.
AB  - One of the strategies to promote an antitumor response is the genetic
      modification of tumor cells to induce expression of costimulatory molecules. We
      have tested the capacity of a soluble form of CD70 molecule (sCD70). After
      construction of a vector carrying the sCD70, we obtained stable sCD70-secreting
      TS/A tumor cells and allogenic MC57 fibroblasts. In all, 45% of wild-type (wt)
      tumors were rejected in immunocompetent mice when transfected sCD70-secreting
      cells were injected three times in the periphery of the wt tumors. Furthermore,
      the sCD70-secreting TS/A cells induced a protective memory against wt TS/A tumor
      growth: 70% of the wt tumors used for the challenge were rejected by mice, which
      had rejected tumors 45 days before in the presence of sCD70-secreting TS/A cells.
      It was also shown that in vitro mock TS/A tumor cell proliferation was inhibited
      by splenocytes harvested from mice injected with TS/A cells expressing CD70.
      Growth kinetics of wt TS/A tumors in immunocompetent versus nude mice suggested
      that T lymphocytes were implicated in the antitumor response, which was confirmed
      by membrane expression of specific markers. The data suggest that injection of
      genetically transfected cells secreting sCD70 in the periphery of wt TS/A tumors
      induces T-cell-mediated inhibition of tumor growth and builds up a protective
      antitumor memory.

PMID- 15153938
TI  - Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in
      ovarian cancer cells independent of the endogenous p53 status.
AB  - Clinical adenoviral p53 gene therapy has been shown by us and others to inhibit
      tumor growth of ovarian cancer with endogenous mutant p53. This study was
      designed to test the cooperative antitumor effect of standard combination
      chemotherapy using paclitaxel and carboplatin together with adenoviral p53 gene
      transfer in the presence of wild-type and mutant p53. Seven ovarian cancer cell
      lines with mutant p53 and seven ovarian cancer cell lines with wild-type p53 were
      tested. An E1-deleted adenovirus type 5 expressing p53 (ACNp53) was used for p53
      gene transfer. p53 gene transfer at 50% transduction efficiency significantly
      reduced IC50 of carboplatin chemotherapy up to 49-fold, of paclitaxel
      chemotherapy up to six-fold, and of paclitaxel/carboplatin chemotherapy up to 19
      fold in the wild-type p53 cell line OV-MZ-5. Synergism between ACNp53 and
      chemotherapy calculated by median-effect analysis was found at low drug
      concentrations in all cell lines independent of the p53 mutational status. In
      conclusion, adenoviral p53 gene transfer significantly increased the sensitivity
      of ovarian tumor cells to paclitaxel, to carboplatin and/or to the combination of
      both.

PMID- 15153939
TI  - Hydrogen peroxide generated at the level of mitochondria in response to
      peroxynitrite promotes U937 cell death via inhibition of the cytoprotective
      signalling mediated by cytosolic phospholipase A2.
AB  - We have studied the relationships existing between delayed formation of H2O2 and
      activation of cytosolic phospholipase A2 (cPLA2), events respectively promoting
      toxicity or survival in U937 cells exposed to peroxynitrite. The outcome of an
      array of different approaches using phospholipase A2 inhibitors, or cPLA2
      antisense oligonucleotides, as well as specific respiratory chain inhibitors and
      respiration-deficient cells led to the demonstration that H2O2 does not mediate
      toxicity by producing direct molecular damage. Rather, the effects of H2O2 were
      found to be upstream to the arachidonic acid (AA)-mediated cytoprotective
      signalling and in fact causally linked to inhibition of cPLA2. Thus, it appears
      that U937 cells exposed to nontoxic concentrations of peroxynitrite are
      nevertheless committed to death, which however is normally prevented by the
      activation of parallel pathways resulting in cPLA2-dependent release of AA. A
      rapid necrotic response, however, takes place when high concentrations of
      peroxynitrite promote formation of H2O2 at levels impairing the cPLA2
      cytoprotective signalling.

PMID- 15153940
TI  - Mice overexpressing human caspase 3 appear phenotypically normal but exhibit
      increased apoptosis and larger lesion volumes in response to transient focal
      cerebral ischaemia.
AB  - Caspase 3 activation has been implicated in cell death following a number of
      neurodegenerative insults. To determine whether caspase genes can affect the
      susceptibility of cells to neurodegeneration, a transgenic mouse line was
      created, expressing human caspase 3 under control of its own promoter. The human
      gene was regulated by the murine homeostatic machinery and human procaspase 3 was
      expressed in the same tissues as mouse caspase 3. These novel transgenic mice
      appeared phenotypically and developmentally normal and survived in excess of 2
      years. Behavioural assessment using the 5-choice serial reaction time task found
      no differences from wild-type littermates. Caspase activity was found to be
      tightly regulated under physiological conditions, however, significantly larger
      lesions were obtained when transgenic mice were subjected to focal cerebral
      ischaemia/reperfusion injury compared to wild-type littermates. These data
      demonstrate that mice overexpressing human caspase 3 are essentially normal,
      however, they have increased susceptibility to degenerative insults.

PMID- 15153941
TI  - p73: regulator in cancer and neural development.

PMID- 15153942
TI  - Redox regulation in disease and ageing.

PMID- 15153943
TI  - Regulation of Chk2 gene expression in lymphoid malignancies: involvement of
      epigenetic mechanisms in Hodgkin's lymphoma cell lines.
AB  - The tumor suppressor Chk2 kinase plays crucial roles in regulating cell-cycle
      checkpoints and apoptosis following DNA damage. We investigated the expression
      levels of the genes encoding Chk2 and several cell-cycle regulators in nine cell
      lines from lymphoid malignancies, including three Hodgkin's lymphoma (HL) lines.
      We found that all HL cell lines exhibited a drastic reduction in Chk2 expression
      without any apparent mutation of the Chk2 gene. However, expression of Chk2 in HL
      cells was restored following treatment with the histone deacetylase inhibitors
      trichostatin A (TsA) and sodium butyrate (SB), or with the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine (5Aza-dC). Chromatin-immunoprecipitation (Chip)
      assays revealed that treatment of HL cells with TsA, SB or 5Aza-dC resulted in
      increased levels of acetylated histones H3 and H4, and decreased levels of
      dimethylated H3 lysine 9 at the Chk2 promoter. These results indicate that
      expression of the Chk2 gene is downregulated in HL cells via epigenetic
      mechanisms.

PMID- 15153947
TI  - It's just my opinion.

PMID- 15153944
TI  - Thrombotic microangiopathy after allogeneic bone marrow transplantation: a
      pathologic abnormality associated with diverse clinical syndromes.

PMID- 15153951
TI  - Collapse of NHS dentistry.

PMID- 15153950
TI  - Fact and fantasy.

PMID- 15153953
TI  - Options for change.

PMID- 15153955
TI  - X-rays.

PMID- 15153958
TI  - New registration process for EU PCDs.

PMID- 15153966
TI  - Research in primary dental care. Part 2: Developing a research question.
AB  - The first step in planning and conducting any research is identifying the
      research question, that is a testable statement of the question which the
      research aims to answer. In this article three distinct types of research
      question are identified: Descriptive questions (for example Who? What? Where?
      When?); Questions of relationships (How are two or more things related?);
      Questions of comparison (often these questions will ask about cause and effect).
      Examples are given of each type of research question. The process of devising a
      research question is described, in particular searching for relevant information,
      and evaluating the quality of the information obtained. A list of useful
      resources is provided.

PMID- 15153967
TI  - Smokeless tobacco cessation guidelines for health professionals in England.
AB  - Smokeless tobacco is used in the UK predominantly by members of the Indian,
      Pakistani and especially Bangladeshi communities. The most commonly used form is
      tobacco mixed with lime and additional psychoactive compounds, most notably areca
      nut. The resulting "quid" is chewed or held in the mouth. Studies from Asia
      indicate that use of this kind of product is linked with an increased risk of
      oral cancers and possibly low birth-weight infants. There is little high quality
      research evaluating interventions to promote cessation of smokeless tobacco use,
      especially of the forms used in the UK. However, what evidence there is suggests
      that advice to stop coupled with behavioural support and counselling may increase
      long-term abstinence rates by some 5-10%. It seems appropriate therefore to
      recommend that dentists, GPs and other relevant health professionals should
      routinely assess and record smokeless tobacco use in patients belonging to
      relatively high prevalence groups, that they ensure that smokeless tobacco users
      know the potential health risks (as well as the health risks of smoking) and that
      they advise them to stop and keep a record of the outcome. Dental professionals
      should also examine the oral cavity of smokeless tobacco users for lesions when
      the opportunity arises. Patients expressing an interest in stopping should be
      referred to specialist smoking cessation services for behavioural support and
      specialists in areas of high smokeless tobacco use will need to ensure that they
      are sufficiently knowledgeable and their services sufficiently accessible to
      these users. There is insufficient evidence to recommend the use of nicotine
      replacement therapy or bupropion to aid smokeless tobacco cessation. Research is
      needed in the UK to quantify the personal and population health risks from
      smokeless tobacco, the benefits of stopping, the effectiveness of interventions
      aimed at promoting cessation and patterns of use, knowledge and attitudes of
      users.

PMID- 15153975
TI  - Assessment of children prior to dental extractions under general anaesthesia in
      Scotland.
AB  - OBJECTIVE: To determine the type of dental assessment service offered to children
      prior to exodontia under chair dental general anaesthesia (CDGA) in the community
      and hospital dental services (CDS, HDS) in Scotland. DESIGN AND SETTING:
      Telephone interviews were conducted with CDS and HDS clinical directors in
      Scotland using a semi-structured questionnaire, with written follow-up
      confirmation. Copies of CDGA referral forms were also requested. RESULTS: All
      clinical directors, or their nominated deputies, participated (n = 21). Almost
      half of interviewees indicated that their area offered a "dedicated" pre-CDGA
      assessment service (n = 10). A range of grades was identified amongst assessors;
      a minority were described as "specialist paediatric staff". The availability of
      CDGA alternatives, including local analgesia and conscious sedation varied.
      Changes to the referral treatment plan were reported to occur "sometimes" or
      "often" by 11 interviewees regarding the anaesthetic used, and by 16 respondents
      regarding the number of teeth extracted. The content of CDGA referral forms was
      diverse. CONCLUSIONS: The method of referral and assessment of children for CDGA
      in Scotland is diverse, partly reflecting geographic limitations and local need.
      Guidance on pre-GA assessment, including use of standardised referral forms, may
      reduce variation and improve the quality of the pathway of care.

PMID- 15153976
TI  - 3D X-ray microscopic study of the extent of variations in enamel density in first
      permanent molars with idiopathic enamel hypomineralisation.
AB  - OBJECTIVE: To measure mineral concentration distributions within teeth with
      idiopathic enamel hypomineralisation, a condition in which developmental defects
      are seen in first permanent molars, and/or incisors. DESIGN: X-ray
      microtomographic and 3D x-ray microscopy. SETTING: UK University, 2001. MATERIALS
      AND METHODS: X-ray microtomographic measurements of the extent of
      hypomineralisation in two affected molars and two contralateral controls
      extracted from the same patient. RESULTS: The control molars were visibly normal.
      The affected molars showed hypomineralised yellow opaque enamel with regions of
      breakdown. X-ray microtomographic images showed; a 20% reduction in mineral
      concentration of affected enamel (most cases involved full enamel thickness);
      hypomineralised enamel had a mineral concentration gradient opposite to that of
      normal enamel; regions of hypomineralisation distributed randomly throughout
      affected teeth, (apart from cervical region which was less severely affected).
      CONCLUSIONS: The pattern of mineral concentration suggests a disturbance during
      the maturation process. Differences in susceptibility of the ameloblasts during
      different stages of dental development may explain the asymmetric distribution of
      the defects. Topical fluoride applications may help promote post eruption
      maturation of the surface layer in these teeth. The use of fissure sealants and
      adhesive materials appears to prevent further breakdown.

PMID- 15153977
TI  - Long-term cost-effectiveness of single indirect restorations in selected dental
      practices.
AB  - OBJECTIVE: To determine the relative cost-effectiveness of alternative methods
      for restoring large tooth substance loss in adults. METHODS: Long-term survival
      estimates and discounted costs for 245 large indirect restorations were used to
      calculate their incremental cost-effectiveness over 15 years when compared with
      direct placement Class II cusp-overlay amalgams and Class IV multisurface resin
      composites, placed in 100 patients from three private dental practices. RESULTS:
      The direct placement restorations were more cost-effective than the indirect
      restorations at all time intervals over the 15-year study period. The full gold
      crown and the ceramometal crown were the most cost-effective indirect posterior
      and anterior restorations respectively. The cast gold onlay and the porcelain
      jacket crown were the least cost-effective indirect posterior and anterior
      restorations respectively. CONCLUSIONS: When clinically practicable, large direct
      placement restorations should be placed initially in preference to indirect
      restorations.

PMID- 15153993
TI  - When's your year end?

PMID- 15153994
TI  - Where the crossovers are: recombination distributions in mammals.

PMID- 15153995
TI  - Regionally specific induction by the Spemann-Mangold organizer.

PMID- 15153996
TI  - Microsatellites: simple sequences with complex evolution.

PMID- 15153997
TI  - Epigenomics: beyond CpG islands.

PMID- 15153998
TI  - Comparative genomics at the vertebrate extremes.

PMID- 15154000
TI  - A nineteenth-century experiment in human selective breeding.

PMID- 15153999
TI  - Integrating ethics and science in the International HapMap Project.

PMID- 15154002
TI  - J Christian Gillin, 1938-2003.

PMID- 15154001
TI  - Valproic acid induces manifestations of simultaneous dopamine enhancement and
      reduction in schizophrenia.

PMID- 15154004
TI  - Expression of cell cycle inhibitor p27Kip1 and its inactivator Jab1 in
      melanocytic lesions.
AB  - Decreased expression of p27 (a cyclin-dependent kinase inhibitor) is an adverse
      prognostic marker in a diverse array of human cancers. The purpose of this study
      was to investigate the expression of p27 and Jab1 (a protein involved in p27
      degradation) in melanocytic lesions, and to identify their possible participation
      in melanoma progression. A tissue microarray was constructed using formalin
      fixed, paraffin-embedded archival tissue blocks of 94 melanocytic lesions
      including 19 benign nevi, 21 dysplastic nevi, 23 melanomas, and 31 metastatic
      melanomas. The expression of p27 and Jab1 was evaluated by immunohistochemistry.
      The association between p27, Jab1, and clinicopathological parameters was
      analyzed using chi2 and Fisher's exact tests. Nonparametric Pearson's rank
      correlation was applied to evaluate the relationship between p27 and Jab1
      expression. p27 was expressed in 15 (88%) nevi, 18 (95%) dysplastic nevi, 11
      (50%) melanomas, and only in four (13%) of the metastatic melanomas (P<0.001).
      Jab1 was expressed in 14 (82%) standard nevi, 18 (95%) dysplastic nevi, 17 (77%)
      melanomas, and 16 (53%) of the metastatic melanomas (P<0.01). In metastatic
      melanomas, there was a negative correlation between p27 and Jab1 expression (r=
      0.166). The low levels of p27 in primary and metastatic melanoma cases may
      explain the high proliferation rate of such lesions. Also, the relative high
      expression of Jab1 in metastatic melanoma, associated with low levels of p27,
      suggests that Jab1 may be involved in survival and proliferation of metastatic
      melanoma cells.

PMID- 15154005
TI  - Differential expression of KIT/PDGFRA mutant isoforms in epithelioid and mixed
      variants of gastrointestinal stromal tumors depends predominantly on the tumor
      site.
AB  - Gastrointestinal stromal tumors (GISTs) form a distinctive group of mesenchymal
      neoplasms, showing differentiation towards the interstitial cells of Cajal.
      Morphologically, GISTs vary from cellular spindle cell tumors to epithelioid or
      mixed, epithelioid and spindle cell variants. The genotypic features underlying
      the morphologic differences of GISTs with vs without epithelioid components are
      not well defined. Acquisition of activating mutations in KIT and PDGFRA has been
      reported as alternative oncogenic events in the pathogenesis of GISTs. In this
      study, a comprehensive KIT and PDGFRA mutational analysis was performed in a
      group of 28 epithelioid/mixed type tumors, in order to explore whether a specific
      KIT/PDGFRA mutational status segregates these neoplasms from spindle cell variant
      GISTs. All GISTs were primary neoplasms, 16 (57.1%) originated from the stomach
      and 12 (42.8%) from other locations. Histomorphologically, 14 GISTs showed an
      epithelioid and 14 a mixed cell type pattern. Mutational analysis included KIT
      exons 9, 11, 13, and 17, and PDGFRA exons 12 and 18 prescreening by denaturing
      high-performance liquid chromatography, followed by direct sequencing. Activating
      mutations of KIT were found in 14 (50%) GISTs, the majority being within exon 11
      (n=11; 39.2%), and the other comprised exon 9 AY 502-503 duplications (n=2; 7.2%)
      and exon 17 Lys --> Aln822 missense mutations (n=1; 3.6%). Most of the KIT mutant
      tumors (n=11; 78.6%) originated from nongastric sites. Seven (25.0%) GISTs with
      no detectable KIT mutations demonstrated PDGFRA mutant isoforms, carrying either
      D842 V mutations (n=5) or exon 18 deletions (n=2). All GISTs harboring PDGFRA
      mutant isoforms originated from the stomach. In seven tumors, no detectable
      mutations were found; all but one of nonmutant tumors initiated from the stomach
      and exhibited an epithelioid morphology. These findings indicate that the
      mutational status of epithelioid/mixed GISTs associates with the anatomical site
      of the tumor.

PMID- 15154006
TI  - Prognostic relevance of histological grade and its components in node-negative
      breast cancer patients.
AB  - Available results highlight the lack of good level of evidence studies on the
      pure prognostic value of histological grade. In the present study, the prognostic
      relevance of histological grade and of its three components, tubule formation,
      nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients
      with node-negative breast cancer treated with locoregional therapy alone until
      early relapse. Histological grade was determined blindly by two observers and
      discordance between evaluations was resolved after joint review using a multihead
      microscope. No relation was observed between histological grade and any of its
      three components and disease-free survival. Conversely, a significant relation
      was observed between histological grade and distant metastasis-free survival (at
      6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as
      overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of
      the three components showed that neither tubule formation nor nuclear
      pleomorphism was associated with prognosis, and only mitotic count strongly
      influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and
      overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a
      much higher subjectivity than any other microscopic evaluation of biomarkers as
      it is the sum of three different morphological features. Within the Italian
      Network for Quality Assessment of Tumor Biomarkers program we observed that
      histological grade is an independent prognostic variable, but also that this role
      is ascribable only to the number of mitotic figures. In conclusion, due to the
      ever smaller size of diagnosed breast cancers, resulting in less cancer tissue
      for biofunctional and molecular analysis, mitotic count evaluated under strict
      quality control conditions seems to be an accurate and feasible prognostic
      variable.

PMID- 15154007
TI  - Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein.
AB  - Invasive micropapillary carcinoma, a tumor with highly infiltrative
      characteristics is defined by a distinctive cleft formation around the neoplastic
      cell clusters which is presumably a result of the detachment of the cells from
      the stroma due to as yet undetermined factors. Ultrastructural examination
      performed on a handful of cases demonstrated an unexpected secretory activity in
      the stroma-facing surface of the cells. MUC1 is a glycoprotein typically
      expressed in the apical surface of normal epithelial cells, responsible for
      maintaining lumen formation. In conventional adenocarcinomas, MUC1 expression is
      largely intracytoplasmic, intercellular, or apical (in glandular areas). The MUC1
      expression pattern was investigated by immunohistochemical staining in invasive
      micropapillary carcinoma of breast (n=11), pancreas (n=5), gynecologic tract
      (n=11) and urinary bladder (n=10). The results were contrasted with the staining
      pattern in conventional carcinomas of the same organs (n=202). In all invasive
      micropapillary carcinoma, MUC1 expression was predominantly in the stroma-facing
      surface of the cell clusters (basal), accentuating the outlines of the
      micropapillary units by forming a distinct band on this surface. In conventional
      carcinoma the labeling was mostly apical in areas with lumen formation and
      intracytoplasmic and intercellular in the poorly differentiated areas. In
      conclusion, in the micropapillary pattern of invasive carcinoma, the expression
      of MUC1, is largely limited to the basal surface of the cells in contrast to
      conventional carcinomas in which MUC1 is largely apical, intracytoplasmic or
      intercellular. This provides support for the reversal of cell orientation as an
      important factor of the morphogenesis and possibly the pathogenesis of invasive
      micropapillary carcinoma. Since MUC1 is known to have a role in lumen formation,
      and has an inhibitory role in the cell to stroma interaction, it is conceivable
      that it is a key factor in the detachment of cells from stroma allowing for the
      dissection of the connective tissue and easing the spread of cells.

PMID- 15154008
TI  - Novel endothelial cell markers in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is characterized by hypervascularity and a propensity
      for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray
      global gene expression data and further validation on a smaller independent
      sample set by reverse transcription-polymerase chain reaction established the
      presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I,
      consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of
      nine unique genes. The expression of the cluster I genes appeared to be
      significantly upregulated in hepatocellular carcinoma compared with normal liver,
      cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular
      carcinoma. The pattern of gene expression of cluster I genes correlated
      positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'.
      Expression of cluster II genes, in contrast, was not significantly different
      between hepatocellular carcinoma and non-neoplastic liver tissues. Studies
      conducted to localize the protein products of these genes by immunohistochemical
      staining of tissue arrays with up to 350 cores of tissues, and by in situ
      hybridization led to the discovery of novel sinusoidal endothelial cell markers
      in hepatocellular carcinoma: podocalyxin-like and regulator of G protein
      signaling-5. Our results underscore fundamental differences not only between
      neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal
      endothelium of hepatocellular carcinoma and normal liver.

PMID- 15154009
TI  - Three independent genetic profiles based on mucin expression in early
      differentiated-type gastric cancers--a new concept of genetic carcinogenesis of
      early differentiated-type adenocarcinomas.
AB  - Recent molecular studies have shown that the genetic profiles of differentiated
      type adenocarcinomas of the stomach are associated with distinct cellular mucin
      phenotypes (gastric- intestinal- and mixed-phenotypes). Therefore, we examined
      whether these cellular mucin phenotypes reflect specific molecular genetic
      alterations, and whether the phenotypes can be used to help categorize the
      intramucosal neoplasias of gastric tumors. We subclassified tumors into four
      cellular phenotypes using immunohistochemical mucin analysis. In all, 62 early
      gastric carcinomas (gastric-phenotype, 13; intestinal-phenotype, 17; mixed
      phenotype, 31; unclassified-phenotype, 1) were examined using a combination of
      polymerase chain reaction microsatellite assays and immunohistochemical analysis
      in order to detect chromosomal allelic losses of multiple cancer-related
      chromosomal loci (1p, 3p. 4p, 5q, 8p, 9p, 13p, 17p, 18q and 22q), microsatellite
      instability (MSI), and overexpression of the p53 protein. In addition, we
      analyzed the relationship between MSI status and hMLH1 promoter hypermethylation,
      which is thought to be a cause of high MSI status. For gastric phenotype cancers,
      the frequency of 3p allelic loss was higher than that of other microsatellite
      markers, whereas 5q allelic loss was frequently found in intestinal phenotype
      cancers. The genetic profile of mixed phenotype cancers is comprised of two
      distinct genetic types: LOH and MSI types. In the former, 5q, 3p and 18q allelic
      losses are seen frequently in intramucosal carcinomas. On the other hand, 17p, 1p
      and 9p allelic losses are associated with the development of submucosal
      carcinomas. MSI was observed only in mixed phenotype cancers (six of 31 mixed
      phenotype cancers). Overexpression of the p53 protein is common in differentiated
      type gastric cancers. In addition, the MSI status of the tumor cells was
      correlated with the extent of hypermethylation of the hMLH1 promoter. We suggest
      that the cellular mucin phenotypes of the differentiated-type adenocarcinomas
      result from distinct genetic alterations.

PMID- 15154010
TI  - Mixed tumors of the vagina: an immunohistochemical study of 13 cases with
      emphasis on the cell of origin and potential aid in differential diagnosis.
AB  - Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an
      admixture of well-differentiated epithelial cells and stromal-type cells in
      various proportions. In contrast to mixed tumors in other anatomic sites, the
      histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical
      profile of 13 examples to explore their histogenesis and determine whether their
      immunohistochemical profile might be useful in the differential diagnosis. The
      panel of antibodies used and the number of cases studied were: AE1/3 (12),
      cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen
      (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13),
      CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for
      AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12
      mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were
      extensively positive for CD10; CD34 was positive in 7/11; and none out of eight
      tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in
      1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal
      markers. The expression of muscle actin (usually extensive), and focal desmin and
      h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial
      component; however, the S-100 negativity and diffuse CD10 expression argue
      against it. Positivity for muscle markers does not help distinguish MTsV from
      smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates
      its use in the differential diagnosis with endometrial stromal tumors, and the
      CD10 and CD34 expression suggests that mixed tumors may arise from a primitive
      pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that
      have been used in gynecologic pathology primarily to aid in establishing the
      smooth muscle or endometrial stromal phenotype of a neoplasm.

PMID- 15154011
TI  - Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among
      pulmonary neuroendocrine tumors.
AB  - A total of 111 pulmonary neuroendocrine tumors comprising 13 typical carcinoids,
      five atypical carcinoids, 44 large-cell neuroendocrine carcinomas and 49 small
      cell carcinomas were immunohistochemically studied for dysregulated cyclin B1
      expression and disruption of the Rb/p16/cyclin D1 pathway (Rb pathway), and the
      results were correlated with tumor proliferation activity and clinical outcome.
      Overexpression of cyclins B1 and D1, respectively, was detected in no and 15%
      typical carcinoids, 20 and 20% atypical carcinoids, 84 and 32% large-cell
      neuroendocrine carcinomas, 84 and 10% small-cell carcinomas. Loss of Rb and p16
      expression, respectively, was observed in no and 14% typical carcinoids, no and
      40% atypical carcinoids, 49 and 18% large-cell neuroendocrine carcinomas, 84 and
      8% small-cell carcinomas. In summary, 29% typical carcinoids, 20% atypical
      carcinoids, 78% large-cell neuroendocrine carcinomas and 93% small-cell
      carcinomas had Rb pathway aberrations. Rb pathway aberration was mostly
      attributed to Rb loss in small-cell carcinomas, while p16 loss and/or cyclin D1
      overexpression besides Rb loss also played an important role in large-cell
      neuroendocrine carcinomas, while cyclin D1 overexpression was the only cause of
      Rb pathway aberration in carcinoid tumors. Thus, both cyclin B1-associated G2/M
      arrest and Rb-mediated G1 arrest are consistently compromised in high-grade large
      cell neuroendocrine carcinoma and small-cell carcinoma, but are generally intact
      or occasionally altered in carcinoid tumor; the mechanisms involved in Rb pathway
      aberration among the tumor categories are different, reflecting a genetic
      divergence among the individual tumor categories. Cyclin B1 expression closely
      correlated with the Ki-67 labeling index either in the individual tumor
      categories or overall tumors (P < 0.0001, r = 0.742), suggesting that cyclin B1
      is one of the key factors regulating cell proliferation in pulmonary
      neuroendocrine tumors. Neither cyclins B1 and D1, Rb, p16, nor Ki-67 correlated
      with patient survival in individual tumor categories, suggesting that the
      prognostic significance of these factors is tumor-type specific.

PMID- 15154013
TI  - Genetic alterations in 102 primary gastric cancers by comparative genomic
      hybridization: gain of 20q and loss of 18q are associated with tumor progression.
AB  - Gastric cancer is one of the most common cancers. Molecular events in the
      carcinogenesis of gastric cancer remain, however, largely undefined. We
      investigated changes in DNA copy number in 102 gastric cancers by CGH. We found
      changes in DNA copy number in all cases, with frequent (> or =30% of patients)
      gains at 20q, 8q, 20p, 7q, 17q, 5p, and 13q. Frequent (> or =20%) losses were
      found at 19p, 18q, 5q, 21q, 4p, 4q, 15q, and 17p. The mean number of total
      alterations was significantly lower in grade 3 and scirrhous-type carcinomas
      (10.81 in grade 3 vs 13.98 in grade 1 and grade 2, 9.31 in scirrhous-type vs
      13.18 in medullary- and intermediate-type). The mean number of losses and total
      alterations were higher in tumors at pT2, pT3 and pT4 (4.68 and 12.77 in pT2,
      pT3, and pT4 vs 2.55 and 9.22 in pT1). The mean number of losses was higher in
      carcinomas with lymph node metastasis (4.83). The mean number of gains and total
      alterations were higher in carcinomas with venous invasion (8.44 and 13.28).
      Several chromosomal alterations were linked in a statistically significant manner
      to specific clinicopathological parameters. Gain of 17q, 20p, and 20q and loss of
      4p were associated with the pattern of the cancer-stroma relationship; loss of
      18q was associated with pT category; gain of 5p was associated with pN category;
      loss of 4q and loss of 21q were associated with lymphatic invasion; gain of 7p
      and loss of 4q and 18q were associated with venous invasion; and loss of 18q was
      associated with pathological stage. These data suggest that gain of 20q and loss
      of 18q might play an important role in the development and progression of gastric
      cancer. Moreover, some genes on 20q and 18q might be target genes of gastric
      cancer.

PMID- 15154012
TI  - CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder
      cancer.
AB  - Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in
      most of the world. On the other hand, squamous cell bladder carcinoma, a rare
      subtype in the Western world, is a common subtype in areas with endemic
      Schistosoma infection. Although schistosomal infection has been reported to
      influence DNA methylation, the pattern and extent of CpG island hypermethylation
      in squamous cell carcinomas remain unknown. In this study, we used methylation
      specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples
      from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with
      Schistosoma and 10 TCC, five of which were Schistosoma-associated). The genes
      analyzed included E-cadherin, DAP-Kinase, O6MGMT, p14, p15, p16, FHIT, APC,
      RASSF1A, GSTP1, RARbeta and p73. Methylation of at least one gene was detected in
      all squamous cell tumors except two, and 45% of samples had at least three
      methylated genes. The average methylation index was 0.24, corresponding to three
      of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated
      than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the
      extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell
      carcinomas (SCC), the overall profile of methylation was similar, with
      Schistosoma-associated cases having a higher methylation index. Our results
      suggest that schistosomal involvement associates with a greater degree of
      epigenetic changes in the bladder epithelium.

PMID- 15154014
TI  - Absence of Mycobacterium avium subsp. paratuberculosis in the microdissected
      granulomas of Crohn's disease.
AB  - The etiology of Crohn's disease remains unknown with inflammatory, infectious,
      and/or genetic causes suspected. Granulomatous inflammation is a characteristic
      feature of the disorder, resembling the tissue response to mycobacterium.
      Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent in
      Johne's disease, a chronic ulcerative intestinal condition in cattle, and has
      been implicated as a likely candidate. We carefully microdissected the granulomas
      from the paraffin-embedded resection specimens of 18 patients with well
      established Crohn's disease. The DNA obtained was PCR amplified for the IS900 and
      IS1311 repeat elements of MAP, PCR product size maintained at 101 and 124 base
      pairs, respectively. Archival tissue from bovine Johne's disease was used as a
      positive control. MAP-specific DNA, confirmed by sequencing and comparison with
      prototype strain sequence, was appropriately amplified from the positive control.
      None of the Crohn's disease cases yielded a positive amplification product,
      failing to support a role for the organism in the pathogenesis of this illness.

PMID- 15154017
TI  - Isolation of human small bowel intraepithelial lymphocytes by annexin V-coated
      magnetic beads.
AB  - Human intestinal intraepithelial lymphocytes (IEL) are important effector cells
      of the mucosal immune system and their study is hampered by the difficulty of
      their isolation. The molecular study of enriched samples of IEL is mandatory in
      the diagnosis of enteropathy-associated T-cell lymphoma and refractory celiac
      sprue. In order to isolate human small bowel IEL, we took advantage of the stress
      that intestinal epithelial cells (IEC) suffer during the conventional initial
      steps of IEL isolation, which induces their apoptosis but not that of IEL. After
      cell individualization by dithiothreitol and ethylenediamine tetraacetic acid,
      two-thirds of human IEC can be stained with Annexin-V due to their surface
      exposure of phosphatidyl serine, a sign of apoptosis. This percentage increases
      to 95% after performing a density gradient to enrich for IEL. This allows for the
      use of Annexin-V-coated magnetic beads, originally designed for the removal of
      dead cells from cell cultures, to obtain >95% pure, 99% viable and untouched IEL
      after two rounds of depletion. This simple procedure has proven useful for the
      isolation of human IEL for functional and molecular studies and can conceivably
      facilitate the diagnosis of intestinal lymphoid malignancies that rely upon the
      study of pure IEL preparations.

PMID- 15154018
TI  - NTP technical report on the toxicity studies of 1,1,2,2-tetrachloroethane (CAS
      No. 79-34-5) administered in microcapsules in feed to F344/N rats and B6C3F1
      mice.
AB  - BACKGROUND: 1,1 ,2,2-Tetrachloroethane was widely used in the production of
      solvents and pesticides. Its production ended in the 1990s, but it is a major
      component of waste sites. We studied the effects of 1,1 ,2,2-tetrachloroethane on
      male and female rats and mice to identify potential toxic hazards to humans.
      METHODS: Because 1,1,2,2-tetrachloroethane can evaporate easily, we enclosed it
      in starch microcapsules and placed them in the feed of rats and mice for 14
      weeks. Male and female rats received up to 4,600 parts per million (ppm) 1,1 ,2,2
      tetrachloroethane (equivalent to 0.46%) and mice received up to 9,100 ppm
      (0.91%). Control animals received empty starch microcapsules in their feed.
      Tissues from more than 40 sites were examined in all control and high-dose
      animals; tissues with lesions were examined in the lower exposure groups until no
      lesions were observed. RESULTS: Rats receiving 1,180 ppm or more 1,1,2,2
      tetrachloroethane and mice receiving 2,300 ppm or more weighed less than the
      control animals. Male and female rats given 1,1 ,2,2-tetrachloroethane had pale
      and diseased livers and also had atrophy of the bone marrow and of the genital
      systems. Male and female mice given 1,1,2,2-tetrachloroethane had lesions of the
      liver and the bile duct. CONCLUSION: We conclude that 1,1,2,2-tetrachloroethane
      at doses greater than 590 ppm in the feed was toxic to the liver of male and
      female rats. In mice, 1,1 ,2,2-tetrachloroethane was already known to cause
      cancer after long-term exposure. In these 14-week studies, 1,1 ,2,2
      tetrachloroethane was toxic to the livers of male and female mice.

PMID- 15154019
TI  - Access of dopamine to the median eminence and brain throughout local vascular
      pathways in sheep.
AB  - In female sheep, estradiol-dependent dopaminergic inhibition exerted by the A15
      nucleus during long days (LD) results in a blockade of reproductive activity.
      This effect could involve the GnRH cell bodies or their terminals in the median
      eminence (ME). However, a vast majority of terminals of the A15 nucleus are
      located in neurohypophysis and only a few in the ME. Previously we demonstrated
      that tritiated dopamine (DA) was transferred from the venous blood of the
      cavernous sinus to the arterial blood supplying the brain. In the present paper,
      we tested the hypothesis that the transferred dopamine could reach further the
      brain and ME. Using isolated sheep heads harvested on short days vs. long days,
      we examined radioactivity in brain tissues following infusion of tritiated
      dopamine into the cavernous sinus. The experiment was performed in ovariectomized
      ewes treated with estradiol (E2) or vehicle. The mean level of radioactivity in
      brain was affected by season (p<0.001) and E2 (p<0.05) and was the highest during
      LD in E2-treated animals. In the next experiment on isolated sheep head we
      measured dopamine and its metabolites levels in blood and pituitary after
      infusion of non-radiolabeled dopamine. We observed an increase (p<0.01) in
      dopamine concentration in arterial blood but not in the brain. The pituitary was
      the only structure examined in which a tendency (p=0.06) towards increased
      dopamine concentration following dopamine infusion was observed. Thus, even if
      part of DA released from terminals within the posterior and intermediate lobes of
      the pituitary reaches the vessels of the ME through local vascular pathways, it
      is unlikely that it could affect the LHRH terminals located in ME. In addition,
      our results suggest that brain capillaries in the isolated head are able to
      maintain a functional blood brain barrier.

PMID- 15154020
TI  - Identifying Depressed Patients With a High Risk of Comorbid Anxiety in Primary
      Care.
AB  - BACKGROUND: Depressive and anxiety disorders are highly prevalent in the primary
      care setting. There is evidence that patients with depression and comorbid
      anxiety are more severely impaired than patients with depression alone and
      require aggressive mental health treatment. The goal of this study was to assess
      the impact of comorbid anxiety in a primary care population of depressed
      patients. METHOD: 342 subjects diagnosed with a DSM-IV-defined major depressive
      episode, dysthymia, or both were asked 2 questions about the presence of comorbid
      anxiety symptoms (history of panic attacks and/or flashbacks). Patient groups
      included depression only (N = 119), depression and panic attacks (N = 51),
      depression and flashbacks (N = 97), and depression and both panic attacks and
      flashbacks (N = 75). Groups were compared on demographics, mental health
      histories, and health-related quality-of-life variables. Data were gathered from
      January 1998 to March 1999. RESULTS: Those patients with depression, panic
      attacks, and flashback symptoms as compared with those with depression alone were
      more likely to be younger, unmarried, and female. The group with depression,
      panic attacks, and flashbacks was also more likely to have more depressive
      symptoms, more impaired health status, worse disability, and a more complicated
      and persistent history of mental illness. Regression analysis revealed that the
      greatest impact on disability, presence of depressive symptoms, and mental health
      outcomes was associated with panic attacks. CONCLUSION: By asking 2 questions
      about comorbid anxiety symptoms, primary care providers evaluating depressed
      patients may be able to identify a group of significantly impaired patients at
      high risk of anxiety disorders who might benefit from collaboration with or
      referral to a mental health specialist.

PMID- 15154021
TI  - Family Support, Self-Rated Health, and Psychological Distress.
AB  - BACKGROUND: Comprehensive health care is becoming an important issue; however,
      little is known about the complex relationships between perceived family support,
      self-rated health, and psychological distress in mixed middle-aged/older primary
      care patient samples. METHOD: In this cross-sectional and predominantly male
      sample of 137 patients attending their appointments at a primary care clinic in a
      Department of Veterans Affairs Medical Center, participants completed several
      questionnaires including the Family Adaptation, Partnership, Growth, Affection,
      and Resolve; the General Health Questionnaire-12; the Symptom Checklist-10; and
      the Primary Care Evaluation of Mental Disorders (PRIME-MD) screening
      questionnaire and interview. Data were collected in 1998. Eighteen percent of the
      participants were diagnosed with a mood disorder, and 15% were diagnosed with an
      anxiety disorder (PRIME-MD diagnoses). RESULTS: Perceived family support and self
      rated health were negatively associated with psychological symptoms and certain
      psychological disorders, while perceived family support and self-rated health
      were positively rated. In addition, the interaction between perceived family
      support and self-rated health was significant (p <.01) in relating to
      psychological symptoms such that psychological symptoms were most elevated in
      participants reporting dissatisfying family support combined with poor self-rated
      health. However, the cross-sectional nature of the study prevents causal
      conclusions from being made. CONCLUSIONS: Physicians and other health care
      professionals are encouraged to assess both the perceived family support and self
      rated health in an effort to conceptualize their patients' problems in a more
      comprehensive manner.

PMID- 15154022
TI  - Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for
      Duloxetine?
AB  - BACKGROUND: Duloxetine is a novel antidepressant that is anticipated to be
      clinically available soon. It exerts simultaneous noradrenergic and serotonergic
      neurotransmitter effects. Because of these influences, it is postulated to have a
      role in management of pain. DATA SOURCES: An Index Medicus search from 1997 to
      2003 was conducted using the search terms duloxetine, Cymbalta, and pain. DATA
      ANALYSIS: Preclinical animal studies suggest that duloxetine may have a direct
      analgesic role. Premarketing studies have emphasized its utility in alleviating
      somatic, specifically pain, complaints among patients with major depression.
      CONCLUSION: Although promising, these results cannot be generalized to patients
      with pain disorders; the reasons for this are discussed herein. While duloxetine
      may be useful among somatizing depressed patients and possibly chronic pain
      patients with comorbid depression, its analgesic role has yet to be elucidated in
      future research.

PMID- 15154023
TI  - Use of an Electronic Medical Record to Facilitate Screening for Depression in
      Primary Care.
AB  - BACKGROUND: Screening programs for depression often fail to improve care because
      of lack of adequate communication and follow-up. The purpose of this study was to
      examine a primary care depression screening program that utilized an electronic
      medical record (EMR) to improve communication and follow-up. METHOD: All adult
      patients in a family practice office were screened for depression using the
      Center for Epidemiological Studies Depression Scale (CES-D) during the period
      March 2000 through March 2001. Screening results were communicated to the primary
      physician via the EMR, and the physician communicated his or her plan back to the
      nurse via the EMR. In this retrospective cohort study, we included all persons
      who screened positive on the CES-D and examined their rate of new psychiatric
      diagnoses, new psychotropic medications, and change in CES-D scores 3 months
      after the initial screening. RESULTS: Of 1092 patients who completed the CES-D,
      247 (22.6%) screened positive for depression. Among these, 35% had a new
      psychiatric diagnosis, 31% were prescribed new psychotropic medications, and 46%
      had a change in psychotropic medications. The vast majority of these were
      depression diagnoses and antidepressant medications. For the 94 persons who
      completed the CES-D at 3-month follow-up, there was a mean decrease in CES-D
      scores of 2.87 (p <.05). CONCLUSION: This study demonstrates a positive impact of
      a depression screening program that utilized an EMR to facilitate communication
      and follow-up. Such programs could help to improve detection and treatment of
      depression in other primary care settings.

PMID- 15154025
TI  - Conquering an Unmasked Social Phobia.

PMID- 15154024
TI  - Compassionate Care of the Terminally Ill.
AB  - LESSONS LEARNED AT THE INTERFACE OF MEDICINE AND PSYCHIATRY: The Psychiatric
      Consultation Service at Massachusetts General Hospital (MGH) sees medical and
      surgical inpatients with comorbid psychiatric symptoms and conditions. Such
      consultations require the integration of medical and psychiatric knowledge.
      During their thrice-weekly rounds, Dr. Huffman and Dr. Stern discuss the
      diagnosis and management of conditions confronted. These discussions have given
      rise to rounds reports that will prove useful for clinicians practicing at the
      interface of medicine and psychiatry.

PMID- 15154026
TI  - Sexual Dysfunction to the Rescue.

PMID- 15154027
TI  - Potential Association Between Risperidone and Cerebrovascular Events.

PMID- 15154028
TI  - The quest for the chemical roots of life.

PMID- 15154029
TI  - High-resolution transmission electron microscopy: the ultimate nanoanalytical
      technique.
AB  - To be able to determine the elemental composition and morphology of individual
      nanoparticles consisting of no more than a dozen or so atoms that weigh a few
      zeptograms (10(-21) g) is but one of the attainments of modern electron
      microscopy. With slightly larger specimens (embracing a few unit cells of the
      structure) their symmetry, crystallographic phase, unit-cell dimension, chemical
      composition and often the valence state (from parallel electron spectroscopic
      measurements) of the constituent atoms may also be determined using a scanning
      beam of electrons of ca. 0.5 nm diameter. Nowadays electron crystallography,
      which treats the digital data of electron diffraction (ED) and high-resolution
      transmission electron microscope (HRTEM) images of minute (ca. 10(-18)g)
      specimens in a quantitatively rigorous manner, solves hitherto unknown structures
      just as X-ray diffraction does with bulk single crystals. In addition, electron
      tomography (see cover photograph and its animation) enables a three-dimensional
      picture of the internal structure of minute objects, such as nanocatalysts in a
      single pore, as well as structural faults such as micro-fissures, to be
      constructed with a resolution of 1 nm from an angular series of two-dimensional
      (projected) images. Very recently (since this article was first written) a new
      meaning has been given to electron crystallography as a result of the spatio
      temporal resolution of surface phenomena achieved on a femtosecond timescale.

PMID- 15154030
TI  - Template synthesis of multi-macrocycles by metathesis reaction.

PMID- 15154031
TI  - Synergistic effects in controlling excited-state photodimerisation using multiple
      supramolecular interactions.

PMID- 15154032
TI  - NH4[BPO4F]: a novel open-framework ammonium fluorinated borophosphate with a
      zeolite-like structure related to gismondine topology.

PMID- 15154033
TI  - Titanocene and zirconocene complexes of a phosphorus analog of an Arduengo's
      carbene: application in the synthesis of 1,3-diphosphafulvenes.

PMID- 15154035
TI  - Step-wise dis-assembly of trimesic acid: mono- and bis(methanol) solvates.

PMID- 15154034
TI  - Synthesis and study of a new diamidodipyrromethane macrocycle. An anion receptor
      with a high sulfate-to-nitrate binding selectivity.
AB  - A new 2,6-diamidopyridinedipyrromethane hybrid macrocycle () has been synthesized
      that shows a high selectivity for dihydrogen phosphate and hydrogen sulfate
      relative to nitrate in acetonitrile solution as judged from UV-vis
      spectrophotometric titrations; this leads to the suggestion that this or related
      systems might find use in nuclear waste remediation applications requiring the
      selective removal of hydrogensulfate from nitrate-rich waste mixtures.

PMID- 15154036
TI  - Effective stabilisation of alpha-helical structures in short peptides with
      acetylenic cross-linking agents.

PMID- 15154037
TI  - Strategies toward improving the performance of fluorescence-based sensors for
      inorganic anions.

PMID- 15154038
TI  - A bidentate borane as colorimetric fluoride ion sensor.

PMID- 15154039
TI  - Imide linked "4 + 4" macrocycles formed by condensation of isophthaloyl
      dichloride and tetra- or penta-fluoroaniline.

PMID- 15154040
TI  - Nano-complex formation of cyclodextrin and azobenzene using supercritical carbon
      dioxide.

PMID- 15154041
TI  - Photocontrol of electron transfer from Zn-porphyrin to an axially bound
      stilbazole-pyromellitic diimide conjugate.

PMID- 15154042
TI  - Ir-Beta zeolite as a heterogeneous catalyst for the one-pot transformation of
      citronellal to menthol.

PMID- 15154043
TI  - Synthesis of two novel dinuclear palladium(I) complexes and studies of their
      catalytic activity in amination reactions.

PMID- 15154044
TI  - Dynamic kinetic resolution: an efficient route to anti alpha-amino-beta-hydroxy
      esters via Ru-SYNPHOS catalyzed hydrogenation.

PMID- 15154045
TI  - Inclusion of C60 fullerene in a M3L2 subphthalocyanine cage.

PMID- 15154047
TI  - Novel biocompatible hydrogel-based amperometric sensor for nitric oxide gas
      detection: towards a non-invasive device.

PMID- 15154046
TI  - First cation radical salt of a tetrathiafulvalene-based phosphine metal complex.

PMID- 15154048
TI  - On the stability of furanopyrimidin-2-one bases in oligonucleotides.
AB  - The fluoresceinated furanopyrimidin-2-one nucleobase incorporated into an
      oligonucleotide undergoes unexpectedly facile hydrolytic ring-opening in aqueous
      buffer at slightly elevated temperatures.

PMID- 15154049
TI  - Recyclable Sonogashira coupling reactions in an ionic liquid, effected in the
      absence of both a copper salt and a phosphine.

PMID- 15154051
TI  - Acoustic coupling at multiple interfaces and the liquid phase response of the
      thickness shear-mode acoustic wave sensor.

PMID- 15154050
TI  - Structural arrangement of two DNA double helices using cross-linked
      oligonucleotide connectors.
AB  - Disulfide cross-linked oligonucleotides, which connect two different sequences of
      DNA strands, have been synthesized and characterized. Two double helices
      connected by two different cross-linked oligonucleotides can be arranged in both
      parallel and antiparallel orientations by addition of the specific complementary
      strands.

PMID- 15154052
TI  - Ruthenium/chloride catalytic system for conjugate addition of terminal alkynes to
      acrylate esters.

PMID- 15154053
TI  - The first solid state structure of a triruthenium polypyridyl complex.

PMID- 15154054
TI  - Efficient protein-ligand interaction by guaranteeing mesospacing between
      immobilized biotins.

PMID- 15154055
TI  - Generation and pH dependent superquenching of poly(amido) carboxylate dendrons
      hosting a single "focal point" pyrene.

PMID- 15154056
TI  - The influence of the loop sequence in binding studies involving cationic
      porphyrins and DNA hairpins.

PMID- 15154057
TI  - First examples of intramolecular Pd(0) catalysed couplings on ortho-iodinated
      meso-phenyl porphyrins.

PMID- 15154058
TI  - Biosynthesis of phomactins: common intermediate phomactatriene and taxadiene.

PMID- 15154059
TI  - Methanolysis of acyl-Pd(II) complexes relevant to CO/ethene coupling reactions.

PMID- 15154060
TI  - Synthesis and structural characterisation of novel bimetallic dipyrromethene
      complexes: rotational locking of the 5-aryl group.

PMID- 15154061
TI  - The measurement of high enantiomeric excesses in chiral liquid crystals using 19F
      NMR and exchangeable protons in 2H NMR.
AB  - It is shown that the 19F spectrum and the 2H NMR spectrum of deuterated protons
      in a chiral liquid crystal medium can be used to measure high enantiomeric
      excesses.

PMID- 15154062
TI  - Preparation of cotton-like silica.

PMID- 15154063
TI  - Solubilization and debundling of purified single-walled carbon nanotubes using
      solubilizing agents in an aqueous solution by high-speed vibration milling
      technique.

PMID- 15154064
TI  - Sidewall modification of single-walled carbon nanotubes using photolysis of
      perfluoroazooctane.

PMID- 15154065
TI  - Highly efficient Pauson-Khand reaction with C60: regioselective synthesis of
      unprecedented cis-1 biscycloadducts.

PMID- 15154066
TI  - [Neurobiology of behavior: exploring the frontier between the mind and the
      brain].

PMID- 15154067
TI  - [Functional psychosis in childhood and adolescence].
AB  - OBJECTIVE: To review the literature about functional psychosis in children and
      adolescents, allowing pediatricians to recognize the pathology in their daily
      work routine. SOURCES OF DATA: Classical textbooks of child and adolescent
      psychiatry; search of MEDLINE and Lilacs databases (1993 to 2003). Computerized
      search methods were combined with manual search of the literature. SUMMARY OF THE
      FINDINGS: This article is structured in topics, trying to define and classify
      psychosis in childhood and adolescence, with schizophrenia being the main
      disorder. The article stresses the difficulties for the diagnosis in children,
      and addresses the main treatment guidelines. CONCLUSION: Schizophrenia beginning
      in childhood, or very-early-onset schizophrenia, is a very rare pathology, almost
      50-fold less frequent than early-onset schizophrenia (appearing at age 15 or
      later). Childhood-onset schizophrenia is a separate disorder, different from
      infantile autism, not only in terms of conceptual issues, but also in terms of
      phenomenology, genetics and associated clinical and neurological issues.

PMID- 15154068
TI  - [Bipolar disorder and depression in childhood and adolescence].
AB  - OBJECTIVES: To provide a historical review of childhood depression and bipolar
      disorder, covering concepts, diagnostic categories, epidemiology, genetic and
      neurobiological aspects as well as predisposing factors and treatment modalities.
      SOURCES OF DATA: Extensive review of the literature on child depression and
      bipolar disorder. SUMMARY OF THE FINDINGS: Child depression and bipolar disorder
      are associated with genetic factors, mood, adverse life events, divorce, academic
      problems, physical and sexual abuse, and neurobiological factors. Treatment
      usually includes medication and psychotherapy. CONCLUSIONS: These are important
      childhood disorders whose diagnosis is often difficult. The identification and
      treatment of depression and bipolar disorder reduces the suffering of affected
      children and adolescents. The pediatrician can intervene by orienting the family
      in mild cases, but must be alert to cases requiring more aggressive treatment.

PMID- 15154069
TI  - [Early manifestations of behavioral disorders in children and adolescents].
AB  - OBJECTIVE: To discuss the early diagnosis of behavioral disorders in childhood
      and adolescence and to provide the pediatrician with practical knowledge about
      the first symptoms of the main behavioral disorders at this age. SOURCES OF DATA:
      PubMed (emphasis on the past decade). SUMMARY OF THE FINDINGS: Pediatricians
      should be prepared to detect behavioral disorders as early as possible. Early
      detection could improve outcome and/or lead to etiologic diagnosis of mendelian
      inheritance disorders, allowing genetic counseling. Early symptoms of pervasive
      developmental disorders, attention deficit/hyperactivity disorder, separation
      anxiety disorder, generalized anxiety disorder, depression, schizophrenia, the
      main eating disorders (anorexia nervosa and bulimia nervosa) and substance use
      and abuse are discussed. CONCLUSIONS: The early symptoms of the main behavioral
      disorders in children and adolescents may appear before the age in which these
      conditions are currently diagnosed. Detection of early symptoms leads to early
      intervention, proper orientation about prognosis and, in some cases, to genetic
      counseling. The comorbidity among these disorders is frequent, and the symptoms
      of one disorder could be the first clue to allow the diagnosis of other
      conditions.

PMID- 15154070
TI  - [Anxiety disorders in childhood and adolescence: clinical and neurobiological
      aspects].
AB  - OBJECTIVE: This article reviews the clinical and epidemiological aspects of
      anxiety disorders in youngsters, as well as current medical and psychological
      treatment strategies. The role of the neurobiological models possibly involved in
      the etiology of these disorders is also discussed. SOURCES OF DATA: MEDLINE
      search of papers published in English from 1981 to 2003. The following key words
      were used: anxiety disorders, neurobiology, childhood, adolescence. SUMMARY OF
      THE FINDINGS: Childhood-onset anxiety disorders are among the most frequent
      psychiatric conditions in children and adolescents. Epidemiological data estimate
      a prevalence of 10% in this population. The neurobiological models involved in
      the etiology of anxiety disorders in youngsters are closely related to
      neuroimaging studies with individuals presenting these pathologies. The role of
      the amygdala in the pathophysiology of these disorders is underscored. To be
      effective, treatment must combine several interventions, such as cognitive
      behavioral, family, and, frequently, drug treatments. CONCLUSIONS: Early
      identification and prompt treatment of anxiety disorders may prevent negative
      consequences, such as school absenteeism and frequent and unnecessary visits to
      pediatric services due to somatic complaints related to anxiety disorders.
      Moreover, it is possible that psychiatric problems could be avoided or attenuated
      in adulthood.

PMID- 15154071
TI  - [The neurobiological bases of obsessive-compulsive disorder and Tourette
      syndrome].
AB  - OBJECTIVE: To describe and discuss evidence-based articles on the neurobiology of
      obsessive-compulsive disorder and Tourette syndrome. SOURCES OF DATA: A review of
      the most relevant papers on the phenomenology, neuroanatomy, neuroimaging,
      genetic and immunological aspects of these two disorders was performed. SUMMARY
      OF THE FINDINGS: Ritualistic behaviors and repetitive thoughts have been
      extensively studied in the last years. The definitions of obsessive-compulsive
      disorder and Tourette syndrome emphasize the existence of a continuum of
      symptoms, with high prevalence in the general population. Neurobiological
      findings have implicated genetic and immunological factors in the etiology of
      these two disorders. CONCLUSIONS: Advances in neuroscience triggered genetic and
      immunological research studies, allowing new perspectives on the treatment of
      obsessive-compulsive disorder and Tourette syndrome patients.

PMID- 15154072
TI  - [Use of psychoactive and antiepileptic drugs: guidelines for pediatricians].
AB  - OBJECTIVE: To review the guidelines for the use of psychoactive and antiepileptic
      drugs in childhood and adolescence. SOURCES OF DATA: Literature review. SUMMARY
      OF THE FINDINGS: The clinical indications, dosage and side effects of
      psychoactive and antiepileptic drugs are presented. The use of psychoactive drugs
      is increasing due to the release of new drugs and to the better understanding of
      emotional disorders in children and adolescents. CONCLUSIONS: The use of
      antiepileptic and psychoactive drugs in childhood requires extensive knowledge
      concerning pharmacokinetics and deleterious side effects. An adequate choice of
      drugs is essential to ensure a successful treatment.

PMID- 15154073
TI  - [Behavior disorders in childhood epilepsy].
AB  - OBJECTIVE: To introduce pediatricians to the psychiatric and behavioral disorders
      that most frequently affect children with epilepsy, qualifying them to diagnose,
      evaluate risk factors and guide the treatment of these children. SOURCES OF DATA:
      MEDLINE (1979 to 2003) and epilepsy clinic at the Neuropediatrics Center,
      Universidade Federal do Parana, Brazil. SUMMARY OF THE FINDINGS: Children with
      epilepsy are at increased risk for behavioral and emotional problems when
      compared to children in the general population and to children with other chronic
      illnesses not involving the central nervous system. Among these problems, the
      following should be emphasized: oppositional defiant disorder, conduct disorder,
      depression, anxiety and attention-deficit/hyperactivity disorder. The main risk
      factors include associated neurological impairment, severe or untreatable
      epilepsy and family, social or environmental problems. Neurobiological factors
      associated with epilepsy are also implicated. The usual treatments with specific
      drugs may be used in children with epilepsy. CONCLUSIONS: Due to the high
      incidence of neuropsychiatric disorders in epileptic children, the pediatrician
      should evaluate the risk factors associated with behavioral, emotional and
      psychiatric problems. The pediatrician is in a position to, and should, solve
      most of these difficulties, due to his/her close relationship with the family. In
      several cases, the associated psychiatric disorders are more harmful to the
      patient's quality of life than the epilepsy itself.

PMID- 15154074
TI  - [Recent advances on attention deficit/hyperactivity disorder].
AB  - OBJECTIVES: To describe the main aspects of attention deficit/hyperactivity
      disorder, including history, epidemiology, etiology, neurobiology, clinical
      features, comorbidities, diagnosis, outcome and treatment. SOURCES OF DATA:
      Comprehensive, non-systematic review of the literature on attention
      deficit/hyperactivity disorder. SUMMARY OF THE FINDINGS: Attention
      deficit/hyperactivity disorder has a neurobiological basis, and is highly
      prevalent in children and adolescents. Treatment is very efficacious, including
      the use of medication in most the cases. CONCLUSIONS: Pediatricians are in a
      privileged position to detect this disorder early and to start the initial
      management of less severe cases and of those not complicated by extensive
      comorbidities.

PMID- 15154075
TI  - [Mental retardation].
AB  - OBJECTIVE: This paper describes recent advances in the neurobiology of mental
      retardation, emphasizing new diagnostic resources provided by cytogenetics,
      molecular testing, and neuroimaging. SOURCES OF DATA: MEDLINE (January 2000
      through October 2003), using the following key words: mental retardation,
      developmental disability, child, and adolescent. Search of the Pediatrics and New
      England Journal of Medicine websites using the key word mental retardation. The
      Online Mendelian Inheritance in Man (OMIM) database was searched for information
      on clinical genetics. SUMMARY OF THE FINDINGS: In October 2003, the number of
      genetic syndromes associated with mental retardation reached 1,149. Considering
      the genetic or environmental and congenital or acquired causes of mental
      retardation, current diagnostic investigation is able to detect the etiology in
      50 to 70% of cases. CONCLUSION: Diagnostic evaluation should follow a stepwise
      approach in order to make rational use of the expensive tools of cytogenetics,
      molecular biology, and neuroimaging.

PMID- 15154076
TI  - [Autism and pervasive developmental disorders].
AB  - OBJECTIVE: To review the current knowledge on neurobiological aspects of autism
      and pervasive developmental disorders, as well as to provide pediatricians with
      up to date information on diagnosis and treatment of autism. SOURCES OF DATA:
      Review of MEDLINE and Internet. SUMMARY OF THE FINDINGS: Autism is the 3rd
      developmental disorder, with an incidence of 40 to 130/100,000 individuals.
      Diagnosis is based on clinical findings, following DSM IV criteria. Neuroimaging,
      investigation of fetal neurological status, and genetic investigation contribute
      towards a better understanding of the neurobiology of autism. CONCLUSION:
      Pediatricians are the first health professional to come in contact with patients
      with autism. Thus, they should be able to diagnose and to coordinate the
      multidisciplinary treatment of these patients.

PMID- 15154077
TI  - [Language and learning disorders].
AB  - OBJECTIVE: To aid health professionals, especially pediatricians, in the
      diagnosis and prevention of language and learning disorders. SOURCES OF DATA:
      Review of the relevant literature published in the past 5 years (MEDLINE and
      textbooks). SUMMARY OF THE FINDINGS: Multiple variables, among them neurological
      diseases, may be related to the etiology of language and learning disorders.
      CONCLUSION: An adequate diagnostic investigation may guide the choice of
      treatment.

PMID- 15154078
TI  - [Environmental influences on child mental health].
AB  - OBJECTIVE: To present an up-to-date review about environmental influences on
      child mental health, describing major risk factors and discussing recommendations
      for intervention by pediatricians. SOURCES OF DATA: MEDLINE, PsycLIT and Lilacs,
      technical books and publications about child development and child and adolescent
      mental health problems and health promotion. SUMMARY OF THE FINDINGS: Children
      are exposed to multiple risk factors, among them high prevalence of disease,
      premature birth, being born from a problematic pregnancy, and living in poverty.
      This negative chain of events increases the risk for emotional problems. The
      negative effects on development and behavior result from the complex interaction
      between genetic, biological, psychological and environmental risk factors. The
      main factors influencing the mental health of children are the social and
      psychological environment. The cumulative risk effect is more important in
      determining emotional problems in children than the presence of one single
      stressor, regardless of its magnitude. CONCLUSION: Environmental factors play an
      important role in the etiology of emotional problems in childhood. An adequate
      clinical investigation allows pediatricians to identify risk factors for the
      development of mental health problems and to ensure early intervention for
      children at risk.

PMID- 15154079
TI  - [Neuropsychological assessment in children].
AB  - OBJECTIVE: To describe the methods used for neuropsychological assessment in
      children, emphasizing aspects of interest to pediatricians, psychologists and
      neurologists. SOURCES OF DATA: Review of the published literature concerning
      neuropsychological assessment, including textbooks and reference manuals. The
      experience of the Neuropsychology Unit at Hospital Sao Lucas, Brazil, is
      described. SUMMARY OF THE FINDINGS: Neuropsychological assessment should not be
      limited to the application of psychometric and neuropsychological tests; it
      should also correlate test findings with the neurological/behavioral disorder and
      establish which part of the brain is likely to be involved. In addition, the
      careful interpretation of result must be associated with an evaluation of the
      individual's current status and of the context in which s/he lives. CONCLUSION:
      The final result of neuropsychological assessment should be a neuropsychological
      profile of the patient, which, in combination with the evaluation of
      neurological/clinical, psychological and social aspects will contribute to
      diagnosis and provide elements to guide the patient in terms of maximizing
      his/her potential.

PMID- 15154080
TI  - Expression of a novel pyridoxal kinase mRNA splice variant, PKH-T, in human
      testis.
AB  - AIM: To identify the genes specifically expressed in human adult and fetal testes
      and spermatozoa. METHODS: A human testis cDNA microarray was established. Then
      mRNAs of human adult and fetal testis and spermatozoa were purified and probes
      were prepared by a reverse transcription reaction with mRNA as the template. The
      microarray was hybridized with probes of adult and fetal testes and spermatozoa.
      The nucleic acid sequences of differentially expressed genes were determined and
      homologies were searched in the databases of GenBank. RESULTS: A novel human
      testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis
      and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was
      1 069 bp in length. The cDNA sequence of this clone was deposited in the Genbank
      (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene,
      HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences
      deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH
      (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison
      of the differential expressions of PKH and PKH-T in testes of different
      developmental stages indicated that PKH-T was expressed in the adult testis and
      spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no
      expression in the testis of Sertoli cell only and partially spermatogenic arrest
      patients. CONCLUSION: PKH-T is a gene highly expressed in adult human testis and
      spermatozoa. It may play an important role in spermatogenesis and could be
      related to male infertility.

PMID- 15154081
TI  - Percoll fractionation of adult mouse spermatogonia improves germ cell
      transplantation.
AB  - AIM: To isolate and transplant germ cells from adult mouse testes for
      transplantation. METHODS: In order to distinguish transplanted cells from
      endogenous cells of recipients, donor transgenic mice expressing green
      fluorescent protein (GFP) were used. Germ cells were collected from the donors at
      10-12 weeks of age and spermatogonia were concentrated by percoll fractionation
      and transplanted into recipient seminiferous tubules that had been previously
      treated with busulfan at 5 weeks of age to remove the endogenous spermatogenic
      cells. RESULTS: Twenty weeks after the transplantation, a wide spread GFP signal
      was observed in the recipient seminiferous tubules. The presence of
      spermatogenesis and spermatozoa was confirmed in sections of 12 out of 14 testes
      transplanted (86 %). However, when germ cells were transplanted without
      concentration the success rate was zero (0/9). CONCLUSION: Germ cells from adult
      mouse testes can be successfully transplanted into recipient seminiferous tubules
      if the cell population is rich in spermatogonia and the percoll fractionation is
      useful in obtaining such a cell population.

PMID- 15154082
TI  - Management of erectile dysfunction: barriers faced by general practitioners.
AB  - AIM: To explore the barriers faced by general practitioners (GPs) in the
      management of patients with erectile dysfunction (ED). METHODS: This was a
      qualitative analysis of focus group discussions and in-depth interviews involving
      28 Malaysian GPs. RESULTS: GPs' perception of ED being not a serious condition
      was a major determinant of their prescribing practice. Doctor's age (younger),
      gender (female), short consultation time and lack of experience were cited as
      barriers. The GPs' prescribing habits were heavily influenced by the feedback
      from the first few patients under treatment, the uncertainty of etiology of ED
      without proper assessment and the profit margin with bulk purchase. Other
      barriers include Patients' coexisting medical conditions, older age, lower socio
      economic status, unrealistic expectations and inappropriate use of the anti
      impotence drugs. Cardiovascular side effects and cost were two most important
      drug barriers. CONCLUSION: The factors influencing the management of ED among the
      general practitioners were multiple and complex. An adequate understanding of how
      these factors (doctors, patients and drugs) interact can assist in the
      formulation and implementation of strategies that encourage GPs to identify and
      manage ED patients.

PMID- 15154083
TI  - Stage-specific localization of transforming growth factor beta1 and beta3 and
      their receptors during spermatogenesis in men.
AB  - AIM: To investigate the stage-specific localization of transforming growth factor
      (TGF) beta1 and beta3 during spermatogenesis in adult human testis. METHODS: The
      localization of TGFbeta1 and beta3 was investigated by immunohistochemical
      staining method employing specific polyclonal antibodies. RESULTS: Both TGFbeta1
      and beta3 and their receptors were preponderant in the Leydig cells. TGFbeta1
      could not be detected in the seminiferous tubules. TGFbeta3 and TGFbeta-Receptor
      (R) I were mainly seen in the elongated spermatids, while TGFbeta-RII in the
      pachytene spermatocytes and weak in the spermatogonia, spermatids and Sertoli
      cells. Only TGFbeta-RII was detected in the Sertoli cells. TGFbeta3, TGFbeta-RI
      and TGFbeta-RII showed a staining pattern dependent upon the stages of the
      seminiferous epithelium cycle. CONCLUSION: TGFbeta isoforms and their receptors
      are present in the somatic and germ cells of the adult human testis, suggesting
      their involvement in the regulation of spermatogenesis.

PMID- 15154084
TI  - Fibrosis of corpus cavernosum in animals following cavernous nerve ablation.
AB  - AIM: To investigate alterations of smooth muscle cells and collagen fibers in
      corpus cavernosum following cavernous neurectomy and its relation to the
      expression of transforming growth factor-beta1 (TGF-beta1). METHODS: Ten adult
      male SD rats (neurectomy group) were subject to a bilateral cavernous nerve (CN)
      resection aseptically under an operating microscope, with 6 sham-operated rats as
      the control. Fifteen weeks after the operation, the penile specimens were
      collected and prepared for quantitative-analyzing of ratio of smooth muscle to
      collagen fibers in corpus cavernosum with confocal microscopy, and for detecting
      the expression of TGF-beta1 by RT-PCR and western-blot. RESULTS: Smooth muscle
      cells that show red color after fluorescent-labeling with tetramethylrhodamine
      isothiocyanate-phalloidin and collagen fibers that produce green autofluorescence
      after paraformaldehyde fixation were clearly identified under the confocal
      microscope. Quantification of fluorescent intensity showed that the ratio of
      smooth muscle to collagen fibers in corpus cavernosum in neurectomy group was
      0.265 +/- 0.125, which was significantly lower than that in sham-operated group
      (0.760 +/- 0.196, P<0.01). RT-PCR and western-blot analyses revealed a
      significantly higher expression of TGF-beta1 in the penile tissues of the
      neurectomy animals than that in sham-operated group. CONCLUSION: Bilateral
      ablation of CN can lead to fibrosis of corpus cavernosum, which may be related to
      an increased expression of TGF-beta1 induced by hypoxia in cavernous tissue after
      denervation.

PMID- 15154085
TI  - Reasons for discontinuation of sildenafil citrate after successful restoration of
      erectile function.
AB  - AIM: To investigate the reasons for discontinuations of sildenafil after the
      successful restoration of erectile function. METHODS: One hundred fifty six
      patients, whose scores of erectile function domain of the 15-item International
      Index of Erectile Function (IIEF) increased to 26 or more after sildenafil
      medication, were included in this study. Six-months after the first sildenafil
      prescription, compliance to medication and the reason for discontinuity were
      reviewed by chart or surveyed by telephone. RESULTS: Fifty-four (34.6 %) of the
      156 successfully treated patients discontinued sildenafil medication. The reasons
      for discontinuance were shortcomings in the partners' or patients' emotional
      readiness for the restoration of sexual life after long-term abstinence (37.0 %),
      fear of possible side effects (18.5 %), recovery of spontaneous erection (14.8
      %), postponement of ED treatment because of co-morbid disease treatment (11.1 %),
      unwillingness to accept drug-dependent erection (7.4 %), high drug cost (3.7 %),
      unacceptability of planned sexual activity (3.7 %) and lack of sexual interest
      (3.7 %). CONCLUSION: The reasons for discontinuing sildenafil medication were
      primarily emotional or relationship-oriented, which indicates that simple
      recovery of a rigid erection is insufficient to restore sexual activity. More
      education about the effects of drug and the counseling of both partners is
      recommended to promote the successful recovery of sexual activity.

PMID- 15154086
TI  - Sexual function of premature ejaculation patients assayed with Chinese Index of
      Premature Ejaculation.
AB  - AIM: To assess the psychometric properties of the Chinese Index of Premature
      Ejaculation (CIPE). METHODS: The sexual function of 167 patients with and 114
      normal controls without premature ejaculation (PE) were evaluated with CIPE. All
      subjects were married and had regular sexual activity. The CIPE has 10 questions,
      focusing on libido, erectile function, ejaculatory latency, sexual satisfaction
      and difficulty in delaying ejaculation, self-confidence and depression. Each
      question was responded to on a 5 point Likert-type scale. The individual question
      score and the total scale score were analyzed between the two groups. RESULTS:
      There were no significant differences between the age, duration of marriage and
      educational level (P> 0.05) of patients with and without PE and normal controls.
      The mean latency of patients with PE and normal controls were 1.6 +/- 1.2 and
      10.2 +/- 9.5 minutes, respectively. Significant differences between patients with
      (26.7 +/- 4.6) PE and normal controls (41.9 +/- 4.0) were observed on the total
      score of CIPE (P< 0.01). Using binary logistic regression analysis, PE was
      significantly related to five questions of the original measure. They are the so
      called the CIPE-5 and include: ejaculatory latency, sexual satisfaction of
      patients and sexual partner, difficulty in delaying ejaculation, anxiety and
      depression. Receiver Operating Characteristic (ROC) curve analysis of CIPE-5
      questionnaire indicated that the sensitivity and specificity of CIPE were 97.60 %
      and 94.74 %, respectively. Employing the total score of CIPE-5, patients with PE
      could be divided into three groups: mild (>15 point) 19.8 %, moderate (10-14
      point) 62.8 % and severe (< 9 point) 16.7 %. CONCLUSION: The CIPE-5 is a useful
      method for the evaluation of sexual function of patients with PE and can be used
      as a clinical endpoint for clinical trials studying the efficacy of
      pharmacological intervention.

PMID- 15154087
TI  - Relaxation of rabbit cavernous smooth muscle to 17beta-estradiol: a non-genomic,
      NO-independent mechanism.
AB  - AIM: To investigate whether estrogen was involved in relaxation of rabbit
      cavernous smooth muscle. METHODS: Relaxation response of the rabbit cavernous
      smooth muscles to 17beta-estradiol (0.3, 3, 30 and 300 nmol/L) were observed in
      vitro. The response of the muscle strips to estrogen after incubation with either
      actinomycin D (10 micromol/L) or L-NAME (10 micromol/L) were also evaluated.
      Inside-out mode of patch clamp in a single smooth muscle cell was applied to
      investigate the Maxi-K channel activities. RESULTS: Estrogen caused a dose
      dependent relaxation of the strips precontracted with norepinephrine. The maximal
      response was noted about 10 minutes after treatment. The estrogen-induced
      relaxation was prevented by neither actinomycin D nor L-NAME, suggesting that the
      response was not mediated by gene transcription or nitric oxide (NO). Application
      of 17beta-estradiol increased the Maxi-K channel activities. CONCLUSION: 17beta
      estradiol may be involved in relaxation of rabbit cavernous smooth muscles via a
      non-genomic and NO independent mechanism. 17beta-estradiol stimulates Maxi-K
      channel of the rabbit cavernous myocyte.

PMID- 15154089
TI  - Sperm DNA damage and its clinical relevance in assessing reproductive outcome.
AB  - The routine examination of semen, which assesses sperm concentration, percentage
      motility and morphology, does not identify subtle defects in sperm chromatin
      architecture. The focus on the genomic integrity of the male gamete has
      intensified recently due to the growing concern that genetic diseases may be
      transmitted via assisted reproductive techniques (ART). Accordingly, the intent
      of this review is to describe the details of the information pertaining to
      mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical
      significance and its relationship with male infertility. Assessment of sperm DNA
      damage appears to be a potential tool for evaluating semen samples prior to their
      use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or
      with the least amount of DNA damage for use in assisted conception. In turn, this
      may alleviate the financial, social and emotional problems associated with failed
      ART attempts.

PMID- 15154088
TI  - Effect of follicle-stimulating hormone on sperm quality and pregnancy rate.
AB  - AIM: To evaluate the possible links between ultrastructural sperm quality and the
      clinical pregnancy rate in infertile males treated with FSH before
      intracytoplasmic sperm injection (ICSI). METHODS: Forty-four infertile males with
      idiopathic oligo-asthenozoospermia were randomly allocated to the treated (n=24)
      and non-treated (control, n=20) groups. Semen analysis was carried out by light
      and transmission electron microscopy (TEM) before and 12 weeks after FSH therapy.
      ICSI was performed in all couples. RESULTS: TEM revealed a significant
      improvement in sperm quality after FSH treatment, particularly in men with their
      partners achieving clinical pregnancy. The pregnancy rate was 33 % in the treated
      group and 20 % in the control. CONCLUSION: RESULTS highlight a positive role of
      FSH therapy in infertile males before ICSI, which was correlated with an
      increased pregnancy rate in treated couples. We believe that improved sperm
      ultrastructure after FSH therapy could positively influence the quality and early
      stage of embryo development, thereby increasing the probability of embryo
      implantation.

PMID- 15154090
TI  - Molecular identity, expression and functional analysis of interleukin-1alpha and
      its isoforms in rat testis.
AB  - Interleukin-1alpha (IL-1alpha) is a proinflammatory cytokine that has also been
      found to act as a paracrine mediator involved in the regulation of testicular
      functions. The present review provides an overview of the role of IL-1alpha in
      testicular physiology. Bioactive IL-1alpha isolated from adult rat testis was
      found to consist of three distinct immunoreactive protein species with apparent
      sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in a thymocyte
      proliferation and steroidogenesis assays with different biopotencies. The
      background of the molecular heterogeneity and processing, secretion and
      regulation of the isoforms of testicular IL-1alpha are discussed. All three
      isoforms have been found to be secreted into the testis tubular lumen and
      interstitial space. We have provided evidence that IL-1alpha is a paracrine
      factor that may be of importance in, e.g., the regulation of Leydig cell
      steroidogenesis. Pathophysiologically, testicular IL-1alpha may contribute to
      testicular relapse of acute lymphocytic leukemia in boys.

PMID- 15154091
TI  - Antifertility effects of methanolic pod extract of Albizzia lebbeck (L.) Benth in
      male rats.
AB  - AIM: To evaluate the antifertility activity of the methanolic pod extract of
      Albizzia lebbeck (L.) Benth in male albino rats. METHODS: The methanolic pod
      extract of Albizzia lebbeck was administrated orally for 60 days at 50, 100 and
      200 mg.kg(-1).day(-1) to male albino rats. Sperm motility and density in cauda
      epididymides were assessed. Biochemical and histological analysis were performed
      in blood samples and reproductive organs. RESULTS: Albizzia lebbeck pod extract
      brought about a significant decrease in the weights of testis, seminal vesicles,
      epdidymis and ventral prostate. The sperm motility and density were significantly
      reduced. There was a marked reduction in the numbers of primary spermatocytes,
      secondary spermatocytes and spermatids. The Sertoli cell count as well as its
      cross sectional surface area were significantly decreased. The Leydig cell
      nuclear area and the number of mature Leydig cells were also significantly
      decreased. The protein, glycogen and cholesterol content of the testis, the
      fructose in the seminal vesicles and protein in the epididymis were significantly
      decreased. The RBC and WBC counts, haemoglobin, haematocrit and blood sugar were
      within the normal range. CONCLUSION: The methanolic extract of A. lebbeck pods
      causes spermatogenic arrest in male albino rats.

PMID- 15154093
TI  - 46, XX male sex reversal syndrome.

PMID- 15154092
TI  - Ischemic glans penis after circumcision.
AB  - A 33-year-old male receiving dorsal penile nerve block (DPNB) for circumcision
      exhibited a postoperative ischemic change over the glans penis. The event
      occurred nearly 24 hours after the procedure. The patient was treated with
      intravenous pentoxifyllin and hyperbaric oxygenation. Total reverse of the
      ischemia was observed. The complications associated with circumcision and DPNB
      were reviewed and discussed.

PMID- 15154094
TI  - American Association of Cancer Research--95th annual meeting. Kinases. 27-31
      March, 2004, Orlando, FL, USA.

PMID- 15154095
TI  - American Association of Cancer Research--95th Annual Meeting. Angiogenesis and
      antibodies. 27-31 March, 2004, Orlando, FL, USA.

PMID- 15154096
TI  - American Association of Cancer Research--95th annual meeting. Highlights. 27-31
      March, 2004, Orlando, FL, USA.

PMID- 15154097
TI  - American Chemical Society--227th Annual Meeting. Antibacterials and anti
      inflammatories. 28 March - 1 April 2004, Anaheim, CA, USA.

PMID- 15154098
TI  - American Chemical Society--227th Annual Meeting. New disclosures. 28 March - 1
      April 2004, Anaheim, CA, USA.

PMID- 15154099
TI  - American Chemical Society--227th annual meeting. Highlights. 28 March - 1 April
      2004, Anaheim, CA, USA.

PMID- 15154100
TI  - American Chemical Society--227th annual meeting. Diabetes. 28 March - 1 April
      2004, Anaheim, CA, USA.

PMID- 15154102
TI  - American Chemical Society--227th Annual Meeting. NMDA receptor. 28 March - 1
      April 2004, Anaheim, CA, USA.

PMID- 15154101
TI  - American Chemical Society--227th annual meeting. Neuroprotection. 28 March - 1
      April 2004, Anaheim, CA, USA.

PMID- 15154103
TI  - Drug discovery summit on anti-inflammation and immune diseases. Immune-mediated
      diseases--second international meeting. 8-9 March 2004, Baltimore, MD, USA.

PMID- 15154105
TI  - Imaging in Oncology--SMi's Inaugural Conference. 17-18 March 2004, London, UK.
AB  - This was the first SMi meeting on the subject of imaging in oncology trials, and
      attracted an enthusiastic audience of approximately 40 delegates from industry
      and academia, including speakers who are highly respected in their fields. The
      meeting covered the use of magnetic resonance imaging and spectroscopy, positron
      emission tomography, ultrasound, computed tomography, single photon emission
      computed tomography, gamma-camera and optical imaging in clinical oncology
      trials. While these modalities have been used clinically for decades, their use
      in oncology trials has not been recognized as potential measures of surrogate
      endpoints, biomarkers and pharmacodynamic endpoints. A number of key issues were
      discussed during the meeting, including the necessity to standardize, validate
      and evaluate these imaging techniques before they can be recognized and widely
      used. Also discussed at some length were the difficulties and problems associated
      with not following imaging protocols in multicenter trials, which can lead to
      unusable data and wasted time and resources.

PMID- 15154104
TI  - Chemokine Receptors and Drug Discovery--SMR meeting. 11 March 2004, Horsham, UK.

PMID- 15154106
TI  - Vaccines--SMi Conference. 24-25 March 2004, London, UK.

PMID- 15154107
TI  - Medical management of endometriosis: a systematic review.
AB  - Endometriosis is an important clinical problem in routine practice. Besides the
      problems of dysmenorrhea, dyspareunia and chronic abdominal pain, women with
      endometriosis are often infertile. We performed a systematic literature review on
      two issues: firstly, we clarified which medical treatment options have been
      investigated in prospective, randomized studies. Secondly, potential future
      treatments, still being preclinically investigated, were examined. A meta
      analysis was not possible as the studies varied too much in their protocols and
      inclusion and exclusion criteria, as well as in the drugs and doses administered.
      Gonadotropin-releasing hormone (GnRH) agonists, progestins and oral
      contraceptives all appear to offer certain advantages for endometriosis patients.
      GnRH agonists appear to be the most effective but they are expensive and long
      term treatment is not possible because of loss of bone mineral density. Estrogen
      add-back may offer some benefit for the clinical complaints of patients, but it
      may reduce the efficacy of GnRH agonists. Progestins have the best clinical
      profile and a good cost-effectiveness balance; however, most studies found that
      they were not as effective as GnRH agonists. Oral contraceptives are only
      effective during treatment and have a high relapse rate after therapy is
      completed. Future options may include the use of GnRH agonists, selective
      estrogen receptor modulators (SERMs) and anti-estrogens, as well as
      immunomodulators.

PMID- 15154108
TI  - Medicinal cannabis: rational guidelines for dosing.
AB  - The medicinal value of cannabis (marijuana) is well documented in the medical
      literature. Cannabinoids, the active ingredients in cannabis, have many distinct
      pharmacological properties. These include analgesic, anti-emetic, anti-oxidative,
      neuroprotective and anti-inflammatory activity, as well as modulation of glial
      cells and tumor growth regulation. Concurrent with all these advances in the
      understanding of the physiological and pharmacological mechanisms of cannabis,
      there is a strong need for developing rational guidelines for dosing. This paper
      will review the known chemistry and pharmacology of cannabis and, on that basis,
      discuss rational guidelines for dosing.

PMID- 15154109
TI  - New pharmacotherapy for epilepsy.
AB  - In the majority of cases, epilepsy develops in three phases: (i) initial brain
      damaging insult (eg, head trauma, stroke, status epilepticus), resulting in (ii)
      epileptogenesis, which in turn leads to (iii) recurrent seizures (epilepsy). The
      current treatment of epilepsy, however, focuses exclusively on the prevention or
      suppression of seizures, ie, the end result of the disease process. Recent
      findings regarding the sequence of neurobiological changes leading to epilepsy
      and its molecular basis have raised the question of whether the disease process
      of epileptogenesis can be prevented, or at least modified in such a way that the
      epilepsy that develops is milder, easier to treat, non-progressive and without
      cognitive decline and drug-resistance. Furthermore, if epilepsy has already
      emerged, can the harmful effects of seizures on the brain be alleviated?
      Experimental data indicate that attenuation of the severity of the initial
      insults associated with seizure activity by anti-epileptic drugs improves the
      outcome by reducing epileptogenesis, resulting in a milder disease. Although
      there are no true anti-epileptogenic compounds that interfere with the molecular
      cascades underlying epileptogenesis, there are several new concepts that offer
      new targets for the treatment of epileptogenesis and disease modification,
      including neurotrophins, neuropeptides, caspase inhibitors and anti-inflammatory
      agents.

PMID- 15154110
TI  - PolyHeme. Northfield Laboratories.
AB  - Northfield is developing PolyHeme, a solution of polymerized hemoglobin, as a
      potential blood substitute for use following surgery and trauma.

PMID- 15154111
TI  - Intranasal apomorphine. Nastech Pharmaceutical.
AB  - Nastech Pharmaceutical Co Inc is developing a nasal formulation of apomorphine
      for the potential treatment of erectile dysfunction and female sexual
      dysfunction.

PMID- 15154112
TI  - Mechanism and timing of mitotic rearrangements in the subtelomeric D4Z4 repeat
      involved in facioscapulohumeral muscular dystrophy.
AB  - Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1A) is associated
      with contractions of the polymorphic D4Z4 repeat on chromosome 4qter. Almost half
      of new FSHD mutations occur postfertilization, resulting in somatic mosaicism for
      D4Z4. Detailed D4Z4 analysis of 11 mosaic individuals with FSHD revealed a mosaic
      mixture of a contracted FSHD-sized allele and the unchanged ancestral allele in 8
      cases, which is suggestive of a mitotic gene conversion without crossover.
      However, in 3 cases, the D4Z4 rearrangement resulted in two different-sized D4Z4
      repeats, indicative of a gene conversion with crossover. In all cases, DNA
      markers proximal and distal to D4Z4 showed no allelic exchanges, suggesting that
      all rearrangements were intrachromosomal. We propose that D4Z4 rearrangements
      occur via a synthesis-dependent strand annealing model that relatively frequently
      allows for crossovers. Furthermore, the distribution of different cell
      populations in mosaic patients with FSHD suggests that mosaicism here results
      from D4Z4 rearrangements occurring during the first few zygotic cell divisions
      after fertilization.

PMID- 15154113
TI  - Whole-genome scan, in a complex disease, using 11,245 single-nucleotide
      polymorphisms: comparison with microsatellites.
AB  - Despite the theoretical evidence of the utility of single-nucleotide
      polymorphisms (SNPs) for linkage analysis, no whole-genome scans of a complex
      disease have yet been published to directly compare SNPs with microsatellites.
      Here, we describe a whole-genome screen of 157 families with multiple cases of
      rheumatoid arthritis (RA), performed using 11,245 genomewide SNPs. The results
      were compared with those from a 10-cM microsatellite scan in the same cohort. The
      SNP analysis detected HLA*DRB1, the major RA susceptibility locus (P=.00004),
      with a linkage interval of 31 cM, compared with a 50-cM linkage interval detected
      by the microsatellite scan. In addition, four loci were detected at a nominal
      significance level (P<.05) in the SNP linkage analysis; these were not observed
      in the microsatellite scan. We demonstrate that variation in information content
      was the main factor contributing to observed differences in the two scans, with
      the SNPs providing significantly higher information content than the
      microsatellites. Reducing the number of SNPs in the marker set to 3,300 (1-cM
      spacing) caused several loci to drop below nominal significance levels,
      suggesting that decreases in information content can have significant effects on
      linkage results. In contrast, differences in maps employed in the analysis, the
      low detectable rate of genotyping error, and the presence of moderate linkage
      disequilibrium between markers did not significantly affect the results. We have
      demonstrated the utility of a dense SNP map for performing linkage analysis in a
      late-age-at-onset disease, where DNA from parents is not always available. The
      high SNP density allows loci to be defined more precisely and provides a partial
      scaffold for association studies, substantially reducing the resource requirement
      for gene-mapping studies.

PMID- 15154114
TI  - High prevalence of SLC6A8 deficiency in X-linked mental retardation.
AB  - A novel X-linked mental retardation (XLMR) syndrome was recently identified,
      resulting from creatine deficiency in the brain caused by mutations in the
      creatine transporter gene, SLC6A8. We have studied the prevalence of SLC6A8
      mutations in a panel of 290 patients with nonsyndromic XLMR archived by the
      European XLMR Consortium. The full-length open reading frame and splice sites of
      the SLC6A8 gene were investigated by DNA sequence analysis. Six pathogenic
      mutations, of which five were novel, were identified in a total of 288 patients
      with XLMR, showing a prevalence of at least 2.1% (6/288). The novel pathogenic
      mutations are a nonsense mutation (p.Y317X) and four missense mutations. Three
      missense mutations (p.G87R, p.P390L, and p.P554L) were concluded to be pathogenic
      on the basis of conservation, segregation, chemical properties of the residues
      involved, as well as the absence of these and any other missense mutation in 276
      controls. For the p.C337W mutation, additional material was available to
      biochemically prove (i.e., by increased urinary creatine : creatinine ratio)
      pathogenicity. In addition, we found nine novel polymorphisms (IVS1+26G-->A,
      IVS7+37G-->A, IVS7+87A-->G, IVS7-35G-->A, IVS12-3C-->T, IVS2+88G-->C, IVS9-36G-
      >A, IVS12-82G-->C, and p.Y498) that were present in the XLMR panel and/or in the
      control panel. Two missense variants (p.V629I and p.M560V) that were not highly
      conserved and were not associated with increased creatine : creatinine ratio, one
      translational silent variant (p.L472), and 10 intervening sequence variants or
      untranslated region variants (IVS6+9C-->T, IVS7-151_152delGA, IVS7-99C-->A, IVS8
      35G-->A, IVS8+28C-->T, IVS10-18C-->T, IVS11+21G-->A, IVS12+15C-->T, *207G-->C,
      IVS12+32C-->A) were found only in the XLMR panel but should be considered as
      unclassified variants or as a polymorphism (p.M560V). Our data indicate that the
      frequency of SLC6A8 mutations in the XLMR population is close to that of CGG
      expansions in FMR1, the gene responsible for fragile-X syndrome.

PMID- 15154115
TI  - Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.
AB  - Elsewhere, we reported the safety and efficacy results of a multicenter phase 3
      trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in
      patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase
      3 double-blind, randomized, and placebo-controlled study received subsequently 1
      mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly
      in an ongoing open-label extension study. Evidence of long-term efficacy, even in
      patients who developed IgG antibodies against rh- alpha GalA, included the
      continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo
      of the extension study and the sustained capillary endothelial GL-3 clearance in
      98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo
      (original placebo group) or 36 mo (original enzyme-treated group). The mean serum
      creatinine level and estimated glomerular filtration rate also remained stable
      after 30-36 mo of treatment. Infusion-associated reactions decreased over time,
      as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients,
      after 30-36 mo of treatment, seven patients tolerized (no detectable IgG
      antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo
      into the extension trial, three patients were withdrawn from the study because of
      positive serum IgE or skin tests; however, all have been rechallenged
      successfully at the time of this report. Thus, enzyme replacement therapy for 30
      36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels,
      sustained endothelial GL-3 clearance, stable kidney function, and a favorable
      safety profile.

PMID- 15154118
TI  - Translating clinical research into health policy.

PMID- 15154116
TI  - Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen
      syndrome.
AB  - Cohen syndrome is a rare autosomal recessive disorder with a variable clinical
      picture mainly characterized by developmental delay, mental retardation,
      microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy,
      severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to
      chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1
      were reported in patients with Cohen syndrome from Finland and other parts of
      northern and western Europe. Here, we describe clinical and molecular findings in
      20 patients with Cohen syndrome from 12 families, originating from Brazil,
      Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or
      compound heterozygous for mutations in COH1. We identified a total of 17 novel
      mutations, mostly resulting in premature termination codons. The clinical
      presentation was highly variable. Developmental delay of varying degree, early
      onset myopia, joint laxity, and facial dysmorphism were the only features present
      in all patients; however, retinopathy at school age, microcephaly, and
      neutropenia are not requisite symptoms of Cohen syndrome. The identification of
      novel mutations in COH1 in an ethnically diverse group of patients demonstrates
      extensive allelic heterogeneity and explains the intriguing clinical variability
      in Cohen syndrome.

PMID- 15154119
TI  - Stressors and self-care challenges faced by adolescents living with type 1
      diabetes.
AB  - The American Diabetes Association currently recommends that all youth with type 1
      diabetes over the age of 7 years follow a plan of intensive management. The
      purpose of this study was to describe stressors and self-care challenges reported
      by adolescents with type 1 diabetes who were undergoing initiation of intensive
      management. Subjects described initiation of intensive management as complicating
      the dilemmas they faced. The importance of individualized and nonjudgmental care
      from parents and health care providers was stressed. This study supports
      development of health care relationships and environments that are teen focused
      not merely disease-centered and embrace exploring options with the teen that will
      enhance positive outcomes.

PMID- 15154120
TI  - Falls in a community of older adults: findings and implications for practice.
AB  - The purpose of this study was to describe the falls that occurred over a 5-year
      period in a group of older adults living in a continuing care retirement
      community (CCRC) and to test two models, one mediating whether or not the
      individual fell and the second the number of falls the individual experienced. Of
      the 312 participants, 177 (57%) residents experienced at least one fall. There
      were a total of 594 falls with the mean number of falls per person being 1.9 (SD
      = 3.0), and the range of falls from 1 to 19. Age, gender, and neurologic disease
      significantly influenced whether or not a fall occurred. Mental health, regular
      use of alcohol, and neurologic problems all significantly influenced the number
      of falls that occurred.

PMID- 15154121
TI  - Knowledge and attitude of nurses caring for patients with HIV/AIDS in Uganda.
AB  - Nurses working in a regional hospital represent the largest group of health care
      workers in Uganda. Four hundred seventy-seven nurses and midwives completed the
      human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      knowledge and attitude surveys (86% response rate). Approximately 95% (n = 452)
      had provided care to HIV/AIDS patients; yet 86% (n = 388) believed resources to
      obtain HIV/AIDS information were inadequate. Fear of contagion was great (47%, n
      = 232). HIV/AIDS knowledge gaps included "precaution and transmission" (64.7%)
      and "agent and immunology" (53.4%). Knowledgeable respondents had less fear of
      contagion. Positive attitudes toward patients with HIV/AIDS were displayed
      despite fear of contagion.

PMID- 15154117
TI  - A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is
      associated with vulnerability to nicotine addiction in men.
AB  - Nicotine is the major addictive substance in cigarettes, and genes involved in
      sensing nicotine are logical candidates for vulnerability to nicotine addiction.
      We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four
      SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of
      901 subjects (815 siblings and 86 parents) from 222 nuclear families with
      multiple nicotine-addicted siblings. The subjects were assessed for addiction by
      both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance
      Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only
      male subjects were included in the final analyses (621 men from 206 families).
      Univariate (single-marker) family-based association tests (FBATs) demonstrated
      that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the
      CHRNA4 gene were significantly associated with a protective effect against
      nicotine addiction as either a dichotomized trait or a quantitative phenotype
      (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results
      of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a
      common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with
      both a protective effect against nicotine addiction as a dichotomized trait (Z=
      3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or
      RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a
      common CHRNA4 haplotype might be protective against vulnerability to nicotine
      addiction in men.

PMID- 15154122
TI  - Evaluating a community-based exercise program for women cancer survivors.
AB  - Approximately 8.9 million cancer survivors live in communities across the United
      States. As advances in cancer therapy continue to improve survival rates, this
      number will increase. Nurses in community, ambulatory, and rehabilitative
      settings are challenged to meet the rehabilitative needs of this population.
      Research indicates that exercise interventions can improve survivors' quality of
      life (QOL). This pilot study examined a community-based exercise program and its
      impact on women cancer survivors' QOL. By using a pretest, posttest one-group
      design, data were collected from two groups on demographics, psychosocial
      adjustment to illness, mood states, fatigue, symptom distress, and overall QOL.
      Findings suggested that for some women exercise improved psychological and social
      well-being. Future research and community-based nursing practice were addressed.

PMID- 15154123
TI  - Resident coping strategies in the nursing home: an indicator of the need for
      dietary services change.
AB  - Inadequate food intake leading to malnutrition impacts up to 85% of nursing home
      residents. Malnutrition can result in compromised quality of life and lead to
      chronic disability, functional decline, increased health care utilization and
      costs, and death. This article examines organizational structure (Perrow, 1979)
      and person-environment fit (Lawton, 1982) as factors in nutritional care of
      nursing home residents. The strategies used by residents to cope with
      organizational food and food service issues, competence, and environmental press
      in the nursing home can alert nurses to the need for changes in dietary services
      to increase food intake and quality of life.

PMID- 15154124
TI  - Physical and psychosocial adaptation of blacks on hemodialysis.
AB  - Roy's Adaptation Model was used to study problems and coping strategies reported
      by 102 blacks on hemodialysis. Although the most frequently identified problems
      were fatigue, muscle soreness, and physical limitations, food and fluid
      restrictions were most bothersome. Participants used multiple strategies to cope
      with the illness and its treatment. Putting trust in God was the most frequently
      identified strategy. These findings can be used to enhance the physical and
      psychosocial assessment of these patients and facilitate the ability of
      clinicians to intervene effectively in helping clients cope with the problems
      that are associated with the illness and its treatment.

PMID- 15154125
TI  - Reducing quantitative data errors: tips for clinical researchers.
AB  - Data errors, or missing and inaccurate data, can compromise research findings.
      Steps can be taken before and during data collection, as well as during data
      entry that will minimize data errors. The purpose of this article is to discuss
      ways to reduce quantitative data errors through thoughtful planning of the data
      collection form, careful reviewing of completed data forms in the field and
      laboratory, and consideration of accurate and efficient data entry with thorough
      verification methods. Clinical researchers are provided with tips and examples
      for reducing data errors.

PMID- 15154126
TI  - How to determine whether a convenience sample represents the population.
AB  - Although convenience samples are used widely by researchers, determination of the
      representativeness of these samples are not generally documented in nursing
      research. Because convenience samples may be biased, this study used a cross
      sectional design and a convenience sample of 141 subjects to describe ways to
      assess this possible bias. Analysis of percentage and average variability
      (variance of the mean) suggested that the study sample represented the research
      setting population. More reports are needed to strengthen the findings of studies
      that have used convenience samples.

PMID- 15154127
TI  - International collaborations in nursing research: the experience of the
      International Hospital Outcomes Study.

PMID- 15154128
TI  - Doctoral preparation in nursing: what are the options?

PMID- 15154129
TI  - Leadership: the next HHR crisis? Part I.

PMID- 15154130
TI  - Hospital reform in France: problems (and sometimes solutions) look much like
      ours.
AB  - The French hospital system is in a state of crisis, its woes not much different
      from what Canadian hospitals experience. In the fall of 2002, the French Minister
      of Health announced a major reform called Hospital 2007, and initiated a wide
      ranging consultation of all stakeholders. Although these consultations resulted
      in some minor changes to the plan, the basic principles of the reform have
      remained. Their implementation has begun and will continue for the next five
      years. Some aspects of this reform allow us to make interesting comparisons with
      the Canadian situation.

PMID- 15154131
TI  - A practical approach to understanding risk of institutionalization in two
      Canadian cities: the Regina Risk Indicator Tool.
AB  - Appropriate utilization of long-term care resources is critical to
      sustainability. This article reports on the evaluation of the Regina Risk
      Indicator Tool conducted by the Calgary Health Region in 2000, including an
      overview of the tool evaluation and a summary of RRIT development within the
      Regina Health District. The RRIT has provided value to Calgary and Regina in
      matching client needs with appropriate community and facility-based services.

PMID- 15154132
TI  - Change readiness for SAP in the Canadian healthcare system.
AB  - The study described in this article was designed to assess the change readiness
      for e-business cost management systems (particularly SAP) within the Canadian
      healthcare system. Previous studies and experts suggest that change readiness is
      an important variable in the application of e-business cost management system
      implementation. One hundred and fifty-four chief executive officers within the
      Canadian healthcare system were surveyed. The response rate was 25.9 percent. The
      survey included a demographic sheet, which supported a better understanding of
      the profile of Canadian healthcare CEOs, their operational budget
      responsibilities, and their feelings toward e-business cost management systems. A
      change readiness instrument reviewed CEOs' change readiness scores in relation to
      four independent variables (implementation of an e-business cost management
      system, healthcare restructuring, budget size and tenure of the CEO). There was a
      significant difference between change readiness scores and the implementation of
      an e-business cost management system. Given the small sample size (n = 40),
      findings are limited. However the study offers more information on this issue
      than is found in the Canadian healthcare literature to date.

PMID- 15154133
TI  - Health policy lessons from down-under: pro-market policies boomerang.

PMID- 15154135
TI  - England's revolutionary change in approach to the electronic health record.

PMID- 15154134
TI  - Injecting excellence into the DNA of healthcare services. New initiatives can
      lead to breakthrough improvements via higher quality at lower costs.

PMID- 15154136
TI  - Maintaining effectiveness while chasing efficiency.

PMID- 15154137
TI  - Enhancing the enterprise. EMRs offer big gains for healthcare organizations of
      all sizes.

PMID- 15154138
TI  - Tech and tenderness. TPA uses predictive modeling based on artificial
      intelligence, wrapped with personalized nurse intervention, to lead high-risk
      patients to medical care.

PMID- 15154139
TI  - What works awards 2003. Birmingham Surgical PC. Alabama surgical practice uses
      Web-based scheduling technology to achieve incredible annual savings by
      leveraging surgeons' availability.

PMID- 15154140
TI  - What works awards 2003. Carilion Health System. A comprehensive EDIS revitalizes
      an IDN's emergency services.

PMID- 15154141
TI  - What works awards 2003. Hampshire OB/GYN. Massachusetts OB/GYN practice improves
      its financial and administrative health with practice management software.

PMID- 15154142
TI  - Breathing new life into home care. Texas hospital remotely monitors the pulmonary
      function of post-transplant pediatric patients.

PMID- 15154143
TI  - Bar coding at the bedside. New England hospital implements an automated point-of
      care medication administration system to reduce medication errors and their
      associated complications.

PMID- 15154145
TI  - Radiology nighthawks via the Internet. Midwest practice offers healthcare
      providers the benefits of an in-house radiologist without the cost of 24-hour
      staffing.

PMID- 15154146
TI  - EMRs/CPRs hotlist.

PMID- 15154144
TI  - When one = zero. Single points of failure can lead to revenue and production
      losses for the unprepared enterprise.

PMID- 15154148
TI  - Integrative health and medicine: an opportunity for leadership and collaboration.

PMID- 15154147
TI  - The year of the EHR?

PMID- 15154149
TI  - Medical science and scientism: when is belief in science a religion?

PMID- 15154150
TI  - A brief evidence-based review of two gastrointestinal illnesses: irritable bowel
      and leaky gut syndromes.

PMID- 15154151
TI  - Healing touch and quality of life in women receiving radiation treatment for
      cancer: a randomized controlled trial.

PMID- 15154152
TI  - Long-term effects of energetic healing on symptoms of psychological depression
      and self-perceived stress.
AB  - The long-term effects of energetic healing were examined in an experimental
      design employing a 3 x 3 factorial MANOVA on symptoms of psychological depression
      and self-perceived stress as measured by the Beck Depression Inventory, Beck
      Hopelessness, and Perceived Stress scales. Forty-six participants were randomly
      assigned to 1 of 3 groups: hands-on Reiki, distance Reiki, or distance Reiki
      placebo, and remained blind to treatment condition. Each participant received a 1
      to 1.5 hour treatment each week for 6 weeks. Pretest data collected prior to
      treatment demonstrated no preexisting significant differences among groups. Upon
      completion of treatment, there was a significant reduction in symptoms of
      psychological distress in treatment groups as compared with controls (P < .05;
      Eta square ranging from .09-.18), and these differences continued to be present 1
      year later (P < .05; Eta square ranging from .12-.44).

PMID- 15154153
TI  - Bridging CAM practice and research: teaching CAM practitioners about research
      methodology.
AB  - The National Institutes of Health (NIH) is continuing to provide funds directed
      to support research in complementary and alternative medicine (CAM). CAM
      providers typically have insufficient knowledge of scientific language or
      research methodology to develop rigorous proposals. Their ability to contribute
      meaningfully as advisors, teachers, or research partners in academic settings, is
      hence limited. To address this issue, we have developed and implemented a 7-week
      course designed to teach community-based CAM providers: (1) to understand
      scientific terminology, research design and grantsmanship; (2) to critically
      evaluate the research literature; and (3) to design pilot studies in areas of
      their interest. In this article, we describe the recruitment process for
      selecting course participants, the course design and instructional process and
      the evaluation results based on qualitative and quantitative methodology. We
      offer suggestions for developing training opportunities both at the local and
      national level that would increase the expertise of CAM providers in
      participating and seeking funded research.

PMID- 15154154
TI  - Mindfulness meditation to reduce symptoms after organ transplant: a pilot study.
AB  - CONTEXT: Solid organ transplant patients require life-long immune suppression
      that can produce distressing side effects and complications. OBJECTIVE: To
      evaluate the potential of Mindfulness-Based Stress Reduction (MBSR) to reduce
      symptoms of depression, anxiety, and sleep disturbance and improve quality of
      life after solid organ transplantation. DESIGN: Longitudinal with evaluations at
      baseline, postcourse and 3-month follow-up. PARTICIPANTS AND SETTING: Kidney,
      lung, or pancreas transplant recipients (N = 20), aged 35 to 59 years, living in
      the community. INTERVENTION: An MBSR class (2.5 hours weekly, for 8 weeks),
      modeled after the program of Jon Kabat-Zinn. Home practice (goal: 45 minutes, 5
      days weekly) was monitored. MAIN OUTCOME MEASURES: Self-report scales for
      depression (CES-D), anxiety (STAI-Y1), and sleep dysfunction (PSQI). RESULTS:
      Nineteen participants completed the course. Findings suggest improvement from
      baseline symptom scores for depression (P = .006) and sleep (P = .011) at the
      completion of the MBSR program. At 3 months, improvement in sleep continued (P =
      .002), and a significant improvement in anxiety scores was seen (P = .043);
      scores for both symptoms demonstrated a linear trend and dose-response
      relationship with practice time. In contrast, depression scores showed a
      quadratic trend, and at 3 months were no longer different from baseline. A
      composite symptom measure was significantly improved at 3-month follow-up (P =
      .007). Global and health-related quality of life ratings were not improved.
      Effects of group support and instructor attention were not controlled, and sample
      size and follow-up time were limited. A randomized trial to overcome these
      shortcomings should be done, as symptom distress in transplant recipients appears
      responsive to MBSR.

PMID- 15154156
TI  - Clinical and quality of life changes in a patient with cervical spinal stenosis
      following chiropractic and homeopathic care.

PMID- 15154155
TI  - Effects of a magnetic field on pelvic floor muscle function in women with stress
      urinary incontinence.
AB  - CONTEXT: Magnetic fields have been found to affect neuromuscular function.
      OBJECTIVE: To study the effect of a magnetic field on measurements of urethral
      function in women with stress urinary incontinence. DESIGN: Observational
      comparative study. SETTING: Consecutive patients in a continence center. PATIENTS
      OR OTHER PARTICIPANTS: Twenty-six consecutive women with diagnosis of stress
      urinary incontinence (SUI). EVALUATION: History and physical examination,
      neurologic exam, urethrocystoscopy, urodynamic testing with water-filling
      cystometry, urethral profilometry at rest, during coughing, and during coughing
      while performing a levator ani contraction (knack maneuver). INTERVENTION: The
      same urodynamic procedures were performed again after the subjects were asked to
      step on specifically designed magnets (magnetic cushion device). STATISTICAL
      ANALYSIS: Two-tailed student t test. MAIN OUTCOME MEASURES: Urethral pressure at
      rest, during coughing, and during coughing while performing a levator ani
      contraction. RESULTS: Mean age was 58.3 years (range: 36-81), mean parity 2.8
      (range: 0-8). The urodynamic parameters measured without and with the use of the
      magnetic cushion device were not found to be different except for the knack
      maneuver. The pressure in the urethra during the knack maneuver while the
      subjects were stepping on the magnetic device was significantly higher than the 1
      obtained without the magnetic field. CONCLUSION: In our patient population, a
      magnetic field increases the efficacy of voluntary levator ani contractions.

PMID- 15154157
TI  - Antihyperglycemic effects of propolis mixed with mulberry leaf extract on
      patients with type 2 diabetes.

PMID- 15154158
TI  - Mitchell Gaynor, MD.  Environmental oncology: an emerging science in cancer
      prevention and treatment. Interview by Jennifer Repo.

PMID- 15154159
TI  - Accuracy of blood glucose estimation by children with diabetes: an investigation
      of repeated practice with growth curve modeling.
AB  - This study used growth curve modeling to explore whether practicing the task of
      estimating blood glucose levels would increase accuracy in children with type 1
      diabetes. It was predicted that accuracy would improve with practice and that
      younger, anxious, poorly adjusted children would improve most. 43 attendees at a
      diabetes summer camp participated. Their mean age was 13.4 yr. (SD = 1.6). All
      were Euro-American, and 22 were girls. Change in accuracy was best represented by
      a quadratic function, and this model fit the data well. Overall, participants'
      accuracy improved initially and then deteriorated. Results indicate that older
      children were more likely to improve and then deteriorate. Younger children were
      more likely to improve and sustain those improvements. Results indicate that
      practicing the task of estimating is not an effective way to increase accuracy
      and may be contra-indicated. These results can help guide research and clinical
      use of glucose estimation in children.

PMID- 15154160
TI  - Revisiting relationships between sex-related variables and continuation in
      counseling.
AB  - This study examined the relationships between three sex-related variables (client
      sex, therapist sex, and dyad matching on sex) and continuation in counseling. 245
      college students who were clients at three university counseling centers
      participated. Consistent with previous studies, women comprised 68.2% of the
      clients seeking services at these counseling centers. Clients' sex was
      significantly related to counseling duration, explaining 2.2% of the common
      variance. Female clients, on the average, attended 1.8 more sessions than male
      clients. However, neither the therapists' sex nor dyad matching on sex was
      significantly related to the duration of counseling. None of the sex-related
      variables correlated with premature termination of counseling. The results have
      implications for providing counseling and outreach services to male students.
      Despite relatively equivalent rates in the incidence of mental health problems,
      female students continue to comprise the majority of clients. Therefore,
      university counseling centers need to communicate their services better to male
      students in need of mental health services.

PMID- 15154161
TI  - Neuropsychological profile in patients with schizotypal personality disorder or
      schizophrenia.
AB  - Neuropsychological impairments have been consistently reported in patients with
      schizophrenia. As little is known whether subjects with schizotypal personality
      disorder exhibit neurocognitive dysfunction similar to that in schizophrenia, we
      assessed the neuropsychological profile of 15 subjects with schizotypal
      personality disorder and compared it with that for 15 patients with schizophrenia
      and for 15 psychiatrically normal volunteers. All participants were administered
      a standard neuropsychological battery assessing language ability, spatial
      ability, visuomotor function, verbal memory, visual memory, auditory attention,
      visual attention, and executive function. Performance on most of the cognitive
      domains was impaired in patients with schizotypal personality disorder but less
      than patients with schizophrenia. Specifically, impairment in verbal memory and
      visuomotor ability in patients with schizotypal personality disorder and patients
      with schizophrenia were comparable, while patients with schizophrenia performed
      worse on the test of executive function than did patients with schizotypal
      personality disorder. As a whole, cognitive deficits in patients with schizotypal
      personality disorder were qualitatively similar to, but quantitatively milder
      than, those for patients with schizophrenia. The results suggest that cognitive
      abilities related to frontotemporal lobe function are disturbed across these
      schizophrenia-spectrum disorders.

PMID- 15154162
TI  - Changes in middle latency auditory evoked potentials during meditation.
AB  - In the present study of middle latency auditory evoked potentials during
      Brahmakumaris Raja Yoga meditation there was a decrease in the peak latency of
      the Na wave (a negative wave between 14 and 19 msec.) during meditation. Since
      the neural generator of this wave lies at the midbrain-thalamic level, from the
      results one can infer that the meditation reduces conduction time at this level.

PMID- 15154163
TI  - Marital status and the risk of suicide: experience from England and Wales, 1982
      1996.
AB  - This analysis examined suicide rates by age, sex, and marital status in England
      and Wales for the period 1982-1996. Never married, widowed, and divorced people
      had higher rates of suicide than those who were married, for both sexes. Among
      the widowed ages 20-39 years, both sexes had the highest rate, and the rate
      decreased with age. The suicide rate for divorced people was similar to those who
      had never married, except for the younger group ages 20-29 years. The male:female
      ratios for the relative suicide risk for never married, widowed, and divorced to
      married for both sexes were statistically significantly different for older
      adults. The decrease in suicide rates observed for the period 1982-1996 in
      England and Wales was mainly attributable to the reduction of suicide rates among
      the widowed and divorced.

PMID- 15154164
TI  - Responsivity to stress in chronic posttraumatic stress disorder due to childhood
      sexual abuse.
AB  - The purpose of this study was to investigate psychological, cardiovascular, and
      neuroendocrine reactivity to standardized stress tests (orthostatic challenge,
      Stroop Color Word Test) in drug-free adult women with chronic PTSD due to
      repetitive childhood sexual abuse. At baseline, the 11 patients showed
      significantly higher mean scores on the Symptom Check List-90 and the Profile of
      Mood States than 13 healthy female controls, whereas baseline cardiovascular or
      hormonal parameters showed no differences between the groups. Also, no
      significant differences were found between the two groups in cardiovascular and
      hormonal responsivity to the stress tests. Thus, in the presence of robust
      psychological differences, the patients with chronic PTSD due to childhood sexual
      abuse did not show alterations in baseline values of neurobiological parameters,
      nor did they react differently to a physical and mental stress test when compared
      to healthy controls.

PMID- 15154165
TI  - Relationships among alcohol consumption, drug use, and goal orientation among
      college students in the southeastern USA.
AB  - Students attending 2 different universities completed a Goals Inventory as well
      as a self-report survey designed to address their use of alcohol and other drugs.
      University 1 was a large, public state-supported school that did not restrict
      alcohol use. From this university were 30 male and 77 female students who ranged
      in age from 18-25 years (M = 20 yr.). University 2 was a small, private church
      affiliated school that enforced a no-alcohol-on-campus policy. This sample
      included 41 male and 50 female students, whose ages ranged from 18-24 years (M =
      19 yr.). More than half of the sample at each school had consumed alcohol at some
      time. While men drank more than women at University 1, the sex-ratio at
      University 2 was not different. Students at University 2 had higher learning and
      performance goal scores, alcohol-use scores, and drug-abuse scores than those at
      University 1. Students at University 2 had higher alcohol-abuse scores. Learning
      goal orientation was inversely related to alcohol-abuse behaviors but only at
      University 1. General alcohol use was inversely related to learning goal
      orientation at University 2. Students at both universities reported drinking to
      relieve tension. Those with a learning goal orientation were reportedly not
      drinking excessive amounts of alcohol. However, the relationship between alcohol
      use and abuse and performance is unclear because students had high performance
      scores at both universities along with high alcohol-use scores.

PMID- 15154166
TI  - What was really learned from Tasker and Golombok's (1995) study of lesbian and
      single parent mothers?
AB  - Limitations of research on gays and family life are discussed, including the low
      statistical power of small samples, a condition which increases the likelihood of
      failing to reject null hypotheses. In particular, it is observed that Fitzgerald
      in 1999 shifted from very tentative arguments in her review of literature to
      rather conclusive statements in her abstract about outcomes for children of gay
      parents. Furthermore, an often quoted 1995 article by Tasker and Golombok, upon
      closer examination, appears to indicate that being raised in a lesbian family
      increases the odds of a child later adopting a homosexual lifestyle even in the
      absence of homosexual attractions. For such reasons, scholars and policymakers
      all should be very cautious in accepting, at face value, at least some of the
      research being reported on gays and family life.

PMID- 15154167
TI  - Correlations of religious belief and practice with college students' tattoo
      related behavior.
AB  - This research builds on a large body of literature which suggests that religious
      belief and practice suppress deviant behavior. Survey data from 520
      undergraduates (64% freshmen and sophomores; 70% female; 80% Euro-American) at a
      large public university in the southwest were examined for whether students'
      strength of religious faith, church attendance, or frequency of prayer correlated
      with their having a tattoo, being interested in tattoos, or being likely to get a
      (or another) tattoo. Analysis showed strength of religious faith had a weak,
      negative correlation with having a tattoo, being interested in tattoos, and being
      likely to get a (or another) tattoo. Church attendance also weakly correlated
      with a reduced interest in tattooing. Since the strength of the numerous
      correlations was very low and barely reached statistical significance, religious
      belief and behavior do not appear to be associated substantively with attitudes
      and behavior regarding tattoos. This suggests increasing cultural acceptance of
      tattooing.

PMID- 15154168
TI  - Response to Lynn, et al.'s "Evaluation of Woodard's theory of perceptually
      oriented hypnosis".
AB  - In this article some misunderstandings of Perceptually Oriented Hypnosis
      presented in the recent evaluation by Lynn, et al. are pointed out. Perceptually
      Oriented Hypnosis emphasizes individual differences naturally occurring in the
      experience of everyday life or being-in-the-world and differentiation as major
      themes to understanding hypnosis. Woodard advocates that qualitative research
      enhances our understanding of hypnotic experiencing and allows us to examine
      hypnotic phenomena that elude the laboratory and control settings.

PMID- 15154169
TI  - Effects of ontogeny on performance of rats in a novel object-recognition task.
AB  - The current experiment investigated ontogenetic forgetting on a novel object
      recognition task similar to that of Besheer and Bevins. 18-day-old pups (n = 49)
      and adult (n = 29) rats were tested at two retention intervals (1 min. or 120
      min.). By employing exclusion criteria which demanded minimum amounts of object
      exploration at training and test, the performance of 18-day-old pups but not that
      of adults was significantly impaired at 120 min. relative to 1 min. Analysis
      indicated that the ontogeny of the learning and memory measured in novel object
      recognition follows a developmental trend similar to that of other forms of
      learning, with older animals remembering more and thus performing better than
      younger animals. Unfortunately, given the extreme variability inherent to the
      task and large N necessary to achieve significance, the use of this task in
      studies of learning, memory, and development is discouraged.

PMID- 15154170
TI  - Tone of postcards in increasing survey response rates.
AB  - This study assessed differences in response rates to a series of three-wave mail
      surveys when amiable or insistently worded postcards were the third wave of the
      mailing. Three studies were conducted; one with a sample of 600 health
      commissioners, one with a sample of 680 vascular nurses, and one with 600
      elementary school secretaries. The combined response rates for the first and
      second wave mailings were 65.8%, 67.6%, and 62.4%, respectively. A total of 308
      amiable and 308 insistent postcards were sent randomly to nonrespondents as the
      third wave mailing. Overall, there were 41 amiable and 52 insistent postcards
      returned, not significantly different by chi-square test. However, a separate chi
      square test for one of the three studies, the nurses' study, did find a
      significant difference in favor of the insistently worded postcards.

PMID- 15154171
TI  - Job control and social support as coping resources in job satisfaction.
AB  - This study examined the effects of active coping on job satisfaction in the
      context of the job demands-control-support model. Participants were 867 employees
      (811 men and 56 women, M age = 35.2 yr.) of a large electrical company in Japan.
      Hierarchical multiple regression analysis examined whether effects of active
      coping on job satisfaction might depend on the extent of coping resources, such
      as job control or social support (supervisor and coworker). Analysis showed that
      the effect of active coping on job satisfaction depended on the extent of
      coworkers' support, not on job control and supervisors' support.

PMID- 15154172
TI  - Workaholism, self-esteem, and motives for money.
AB  - This study examined correlations of workaholism types among 69 male and 86 female
      undergraduate business students. Three types were considered (Work Addicts, Work
      Enthusiasts, and Enthusiastic Addicts) using measures developed in 1992 by Spence
      and Robbins. Correlates included personal demographics, self-esteem, and motives
      for money. Work Addicts indicated significantly lower self-esteem than both Work
      Enthusiasts and Enthusiastic Addicts; the workaholism types mentioned above did
      not differ on motives for money, however.

PMID- 15154173
TI  - Machiavellianism scores and self-rated performance of automobile salespersons.
AB  - Machiavellianism (Mach-B) was positively correlated with self-reported number of
      vehicles sold and income in two samples of 80 car salespersons. The Mach-B scale
      showed higher internal consistency and significant relationship with sales
      performance. The Mach IV scale, used for one of two samples, showed low internal
      consistency and a nonsignificant relationship with performance. The results
      provided partial support for earlier findings. Research designed to clarify this
      finding is required.

PMID- 15154174
TI  - Sex differences in memory estimates for pictures and words with multiple recall
      trials.
AB  - Undergraduate students (23 men and 23 women) provided memory performance
      estimates before and after each of three recall trials involving 80 stimuli (40
      pictures and 40 words). No sex differences were found across trials for the total
      recall of items or for the recall of pictures and words separately. A significant
      increase in recall for pictures (not words) was found for both sexes across
      trials. The previous results of Ionescu were replicated on the first and second
      recall trials: men underestimated their performance on the pictures and women
      underestimated their performance on the word items. These differences in
      postrecall estimates were not found after the third recall trial: men and women
      alike underestimated their performance on both the picture and word items. The
      disappearance of item-specific sex differences in postrecall estimates for the
      third recall trial does not imply that men and women become more accurate at
      estimating their actual performance with multiple recall trials.

PMID- 15154175
TI  - Development of a short form of the Treatment Evaluation Inventory for
      acceptability of psychological interventions.
AB  - The Treatment Evaluation Inventory of Kazdin, French, and Sherick is a 19-item
      measure of the perceived acceptability of behavioural treatments. Development of
      two brief forms was based on data from two sources. For Study 1, data from 218
      completed questionnaires were used to develop internally consistent brief scales.
      In Study 2 internal consistency and the validity of the brief forms were
      estimated for a set of 131 questionnaires. Item reduction was achieved by
      analysis of item-total minus item correlations. Brief forms with 3, 6, 9, and 12
      items were proposed. Their internal consistency (Cronbach alpha) and construct
      validity were based on correlations of scores on each short form with the full
      scale scores and on comparing means of different forms. Discriminant validity was
      based on the difference between two groups (estimated effect size 0.7). Scores
      for all forms showed high internal consistency and correlated highly with total
      scale scores. Only the 12-item brief scale yielded mean scores similar to the
      full scale. The 3-item form could be used as a quick screen, and the 12-item form
      for more intensive purposes as it is most similar to the full-scale.

PMID- 15154176
TI  - Test-retest reliability of the Holyoake Codependency Index with Australian
      students.
AB  - The Holyoake Codependency Index is a 13-item self-report measure of three aspects
      of codependency: External Focus, Self-sacrifice, and a sense of being overwhelmed
      by another person's problematic behavior (termed Reactivity). Previous studies
      have supported internal validity and the internal consistency and construct
      validity of the subscales. The present scores for 59 students indicate full scale
      test-retest reliability of .88 and for subscales (.76 to .82) over a 3-wk.
      interval.

PMID- 15154177
TI  - Some normative data on mental health professionals' attitudes about racial
      minorities and women.
AB  - Although codes of ethics of the mental health professions and the recently
      developed race- and gender-specific models of counseling and psychotherapy
      stipulate positive and accepting attitudes toward racial minorities and women,
      formal assessment of these attitudes has been hindered by the absence of
      appropriate measurement tools and generalizable data. This study provides some
      normative data by reporting responses of 705 psychologists and social workers to
      the Quick Discrimination Index, a psychometrically sound 23-item self-report
      measure previously administered to several different professional groups.
      Analysis indicated psychologists and social workers reported particularly
      positive attitudes toward racial minorities and women but expressed the same
      racial and sex contradictions, ambivalences, and vulnerabilities reported by the
      general public.

PMID- 15154178
TI  - Comments on "The effects of leader-member exchange and differential treatment on
      work unit commitment": distinguishing between neutralizing and moderating
      effects.
AB  - Van Breukelen, Konst, and van der Vlist in 2002 examined how members' perceptions
      of differential treatment from the leader affect the relationship between Leader
      Member exchange and work unit commitment. This paper offers commentary, with
      specific focus on the judgment call for examining continuous effects across all
      levels of differential treatment. To justify the role of differential treatment
      as a neutralizer that weakens the influence of Leader-Member exchange on work
      unit commitment, the regression coefficients of work unit commitment on Leader
      Member Exchange should be examined continuously with discriminable differential
      treatment. As a caution against using "neutralizer" based on the research results
      presented, "moderator" is suggested as the more appropriate descriptor of the
      role that differential treatment played. Also, the nature of the interaction
      between Leader-Member exchange quality and work unit commitment is explored,
      suggesting research should focus more on the main effects.

PMID- 15154179
TI  - Redefining delusion based on studies of subjective paranormal ideation.
AB  - The DSM-IV definition of delusion is argued to be unsatisfactory because it does
      not explain the mechanism for delusion formation and maintenance, it implies that
      such beliefs are necessarily dysfunctional (pathological), it underestimates the
      social component to some delusions, and it is inconsistent with research
      indicating that delusions can be modified through techniques such as
      contradiction, confrontation, and cognitive-behavioral therapy. However, a well
      replicated mathematical model of magical/delusional thinking based on a study of
      paranormal beliefs and experiences is consistent with the hypothesis that
      attributional processes play a central role in delusion formation and
      maintenance. The model suggests attributional processes serve the adaptive
      function of reducing fear associated with ambiguous stimuli and delusional
      thinking is on a continuum with nonpathological forms. Based on this collective
      research an amendment to the definition of delusion is proposed and its clinical
      implications are addressed.

PMID- 15154180
TI  - A simple computational alternative to analysis of variance formulas for
      estimating the k-judge reliability.
AB  - Formulas requiring the computation of only three standard deviations are
      presented for computing the interjudge reliability coefficient for any number of
      judges. These formulas yield coefficients identical to those obtained from a one
      way repeated-measures analysis of variance. Even researchers with small handheld
      calculators can use this simple approach.

PMID- 15154181
TI  - Cross-national stability of a leadership model.
AB  - This study explored 60 Greek-Cypriot managers' perceptions of different
      dimensions of leadership. Analyses using structural equation modeling were
      performed to examine the invariance of the Flamholtz six-factor leadership model.
      The same leadership styles observed in samples from countries previously studied
      were present in the sample from Cyprus. In terms of the importance assigned to
      each style of leadership, Cypriot managers emphasized the more directive styles
      to a greater extent than other styles.

PMID- 15154182
TI  - Emotion and style in an English translation of the Quran.
AB  - An English translation of the Quran was studied in terms of word use patterns,
      emotionality of words, and style. Variables were assessed with the help of
      computer programs and the Dictionary of Affect in Language. On the basis of words
      used at unusually high frequencies, the translation of the Quran was seen to be
      emphatically about Allah, his Prophets and Message, and believers. The
      translation of the Quran was slightly less Pleasant and Active in emotional tone
      than everyday English and also less concrete. It contained an unusual number of
      negatives and was repetitive but did not contain many rare or long words.
      Significant differences were noted between chronologically Early and Late suras
      (chapters) in terms of emotion, style, and word use. An inflection point was
      identified in the time-line partway through the Meccan suras of the Quran.

PMID- 15154183
TI  - Reconsidering the relationship between parenting and religiosity.
AB  - This study examined the relation between religiosity and parenting. 311 parents
      from the Flemish-speaking part of Belgium completed the Post-critical Belief
      Scale and reported on their style of parenting. Scores for religiosity (as
      measured by the Exclusion vs Inclusion of Transcendence dimension) were not
      significantly correlated with parenting styles. In contrast, the way in which
      religious contents are processed (as measured by the Literal vs Symbolic
      dimension) was significantly correlated with dimensions of parenting style.

PMID- 15154184
TI  - Latent relationships of fluid, visual, and simultaneous cognitive tasks.
AB  - Horn's 1989 fluid intelligence and Luria's 1966 simultaneous processing have been
      represented in various cognitive assessment batteries. Although related, these
      concepts are purported to measure distinct cognitive functions; fluid
      intelligence refers to deductive reasoning whereas simultaneous processing refers
      to understanding complex relationships among gestalts. The current study explored
      the factor structure of known fluid and simultaneous tests along with visually
      complex new tests. A total of 56 children in Grades 1 through 5 were administered
      tests from the Kaufman Assessment Battery for Children, Elliott's Differential
      Abilities Scales, and two experimental tasks. Findings suggest that (1) the two
      experimental subtests were psychometrically viable, (2) when analyzed as a two
      factor structure, fluid and visual processing components were pronounced, and (3)
      when analyzed as a single-factor structure, simultaneous processing emerged.
      These findings indicate simultaneous processing may be a blend of fluid and
      visual components.

PMID- 15154185
TI  - Three stress groups on their stressors and reactions to stressors in five
      studies.
AB  - A comparison of means and SDs for responses from three stress groups on the
      Student-life Stress Inventory in five studies over 13 years.

PMID- 15154186
TI  - Internal consistency reliability and construct validity of an Arabic translation
      of the shortened form of the Fennema-Sherman Mathematics Attitudes Scales.
AB  - A sample of 480 (246 boys and 234 girls) students in Grade 11 in the United Arab
      Emirates completed an Arabic version of the shortened form of the Fennema-Sherman
      Mathematics Attitudes Scales. A factor analysis of the intercorrelations of
      responses to 51 items indicated the same general factors as in the original
      study. Internal consistency estimates of the reliability of scores on the total
      scale and on each scale for the short form were acceptable, with coefficients
      alpha ranging from .72 to .89.

PMID- 15154187
TI  - Divergent, criterion-related, and discriminant validities for the Kuwait
      University Anxiety Scale.
AB  - Three analyses were carried out. Analysis I estimated the correlation between the
      total score of the Kuwait University Anxiety Scale and a self-rating scale of
      happiness with large sample of male (n = 1,312) and female (n = 1,272) Kuwaiti
      adolescents. Pearson product-moment correlations were -.43 and -.44 (p < .001)
      for boys and girls, respectively, suggesting divergent validity of the anxiety
      scale. Analysis II examined the correlations between scores on the Kuwait
      University Anxiety Scale and the Somatic Symptoms Inventory for a nonclinical
      sample of women (n = 30), and female outpatients with anxiety disorder (n = 30).
      Pearson product-moment correlations were, respectively, .85 and .53, (p < .001),
      which support the criterion-related validity of the Kuwait University Anxiety
      Scale with respect to the Somatic Symptoms Inventory. In Analysis III a sample of
      60 male and female outpatients with anxiety disorder and 60 nonclinical
      participants were matched on age, education, and occupation. All responded
      individually to the Kuwait University Anxiety Scale. Significant differences
      among groups, especially noticeable for men, support the discriminant validity of
      the scale. So, the clinical as well as research use of the scale can be
      recommended. By and large, the divergent, discriminant, and criterion-related
      validities of the scale have been adequately supported so subsequent replication
      is expected.

PMID- 15154188
TI  - Family conflict tendency and ADHD.
AB  - A lack of perseverance, poor attention, and poorly modulated behaviour are
      important criteria of Attention Deficit Hyperactive Disorder (ADHD). Instructions
      often have to be repeated, sometimes even by different family members before a
      child with ADHD attends and complies. We hypothesised that a child with ADHD
      might cause less disagreement in families with almost no conflicts. Responses to
      the Mannheim Parents Interview and teacher's form of the Conners scale completed
      by families of 15 boys (ages 6 to 12 years), diagnosed with ADHD were compared
      with those of a matched, healthy control group of 15 boys. Parents completed a
      form assessing the family's cooperation and child-rearing practices. Having few
      family conflicts, i.e., almost no Verbal Disagreement may reduce Physical
      Punishment and Anger and Disregard and augment the Openness to another's needs
      and, for that reason, have protective effects on children's behaviour modulation.

PMID- 15154189
TI  - Desire for control and communication-related personality variables.
AB  - In a sample of 95 university students, scores on a measure of desire for control
      correlated .37 with willingness to communicate, supporting the notion of control
      as a motive for communication and also correlated .43 with self-perceived
      communication competence but not with communication apprehension.

PMID- 15154190
TI  - Some factors in condom use amongst first-year Nigerian University students and
      black and white South Africans.
AB  - A questionnaire was administered to 213 sexually active first-year Nigerian
      university students and 150 Black and 150 White South African adults. Nigerian
      students gave 90% correct answers on 6 of the 10 items of a measure of condom
      knowledge (M = 6.1). The most common mistakes with respect to condom use were
      ignorance about putting a condom on just before ejaculation (37%), the use of an
      oil-based lubricant with a condom (29%), and when to take off a condom (28%). For
      the South African sample utility of the Health Belief Model and Theory of
      Reasoned Action for HIV prevention could be confirmed by intention to use
      condoms. Race and preventive benefits were predictive for current condom use.
      Findings have relevant implications for developing culturally diverse HIV
      intervention programs if confirmed with larger diverse groups.

PMID- 15154191
TI  - Psychological effects of attack on the World Trade Center: analysis before and
      after.
AB  - Four different studies using a total sample of 711 from the same New York City
      student population tested a model that has emerged from previous research on
      disasters. The model suggests that postdisaster psychological distress is a
      function of exposure to the disaster, predisaster psychological distress, acute
      distress following the disaster, time elapsed between disaster and observation of
      distress, and additional traumatic experiences since the disaster. Although
      findings replicate those of previous cross-sectional studies regarding
      association of exposure and distress after the disaster, before and after studies
      did not detect an effect on postdisaster psychological distress of the World
      Trade Center attack. Great caution must be used in attributing elevated
      psychological distress observed postdisaster to the effects of the disaster.

PMID- 15154192
TI  - Trends and monthly variations in the historical record of suicide in Japan from
      1976 to 1994.
AB  - Monthly suicide rates in Japan were analyzed for the period from 1976 to 1994 to
      clarify trends and recurring effects. The data were separated by sex, and the
      least-squares method was used. The major findings were (1) a significant positive
      correlation between unemployment rate and suicide rate for both sexes, (2) the
      suicide rate was highest in April for both sexes, and (3) an upsurge in male
      suicide mortality was noted from 1983 to 1990. These findings may well be
      associated with socioeconomic factors as well as neurobehavioral variables.

PMID- 15154193
TI  - Construction of a scale for measuring development of moral judgement.
AB  - The present research is a part of a study done to develop an objective measure of
      the development of moral judgement according to Kohlberg's theoretical construct.
      The Padua Scale of Moral Judgement and the relationship between empirical data
      and theory are presented. The scale was constructed from responses to the
      Sociomoral Reflection Measure-Short Form derived from Kohlberg's Moral Judgement
      Interview. Reliability and validity of the new scale as well as group age and sex
      differences were examined.

PMID- 15154194
TI  - Frames of reference for self-evaluation of ability in mathematics.
AB  - Measures of eight frame-specific self-evaluations of ability in mathematics were
      used to predict general mathematics self-concept and self-efficacy. Participants
      were 900 Norwegian students in Grade 6 (n = 277), Grade 9 (n = 236), Grade 11 (n
      = 263), and adult students attending senior high school (n = 124). Four items
      measured frame-specific self-evaluation of achievement based on external frames
      of reference whereas four items measured frame-specific self-evaluation based on
      internal frames of reference. Regression analyses were used to test relations
      between the frame-specific self-evaluations and general mathematics self-concept
      and self-efficacy. The analyses indicated that self-evaluation based on
      comparison with other students in class (an external frame of reference) and on
      comparison of mathematics achievement with achievement in other school subjects
      (an internal frame of reference) were robust predictors of both mathematics self
      concept and self-efficacy. The analyses also indicated that students are using
      multiple frames of reference when evaluating their mathematics ability.
      Implications of the result for the internal-external frame of reference model are
      discussed.

PMID- 15154195
TI  - Sex, perceptions of attractiveness, and sensation seeking and ratings of the
      likelihood of having sexually transmitted diseases.
AB  - Association of attractiveness, sex, and sensation seeking with perceptions of
      sexually transmitted diseases were examined. Subjects (64 women and 56 men) were
      given a picture and brief description of a target and asked to rate the accuracy
      of statements based on information provided. Pictures depicted a man or woman
      previously rated as attractive or unattractive by volunteers. The hobbies listed
      skydiving and rock climbing for high sensation seekers and reading and listening
      to music for low sensation seekers. Analysis indicated a significant three-way
      interaction with the attractive male targets described as high sensation-seeking
      and being perceived by men as most likely to have a sexually transmitted disease.

PMID- 15154196
TI  - Loneliness in cancer and multiple sclerosis patients.
AB  - Loneliness is a universal social phenomenon often producing debilitating effects
      on many aspects of human functioning. The present study compared the qualitative
      aspects of loneliness in two terminally ill samples to that of a more healthy
      sample. 329 multiple sclerosis and 315 cancer patients, as well as 391 nonrandom
      healthy participants answered a 30-item questionnaire on loneliness. Analysis
      indicated the experience of loneliness which characterizes multiple sclerosis and
      cancer patients differs from that of the more healthy group.

PMID- 15154197
TI  - Toward a phenomenology of trance logic in posttraumatic stress disorder.
AB  - Some induction procedures result in trance logic as an essential feature of
      hypnosis. Trance logic is a voluntary state of acceptance of suggestions without
      the critical evaluation that would destroy the validity of the meaningfulness of
      the suggestion. Induction procedures in real and simulated conditions induce a
      conflict between two contradictory messages in experimental hypnosis. In military
      induction the conflict is much more subtle involving society's need for security
      and its need for ethics. Such conflicts are often construed by the subject as
      trance logic. Trance logic provides an opportunity for therapists using the
      phenomenology of "presence" to deal with the objectified concepts of "avoidance,"
      "numbing" implicit in this kind of dysfunctional thinking in Posttraumatic Stress
      Disorder. An individual phenomenology of induction procedures and suggestions,
      which trigger trance logic, may lead to a resolution of logical fallacies and
      recurring painful memories. It invites a reconciliation of conflicting messages
      implicit in phobias and avoidance traumas. Such a phenomenological analysis of
      trance logic may well be a novel approach to restructure the meaning of trauma.

PMID- 15154198
TI  - Concordance among readers of self-help books about important ideas.
AB  - Amount of agreement among readers about the relevant information in a self-help
      psychology book was measured to assess whether readers' choices are unique or
      overlapping. 15 men and 14 women attended two 1-hr. sessions in which they read
      and marked relevant information in the first 60 pages of a self-help psychology
      book. Comparison of the amount and pattern of marking across pages and lines on
      five specific pages showed that there was a statistically significant amount of
      agreement on which pages contained relevant ideas and which lines contained
      important concepts. There were no differences between men and women.

PMID- 15154199
TI  - Help-seeking for mental health problems of children: preferences and attitudes in
      the United Arab Emirates.
AB  - Parental attitudes, religious beliefs, and other sociocultural factors have all
      been recognized to influence help-seeking patterns in relation to child
      psychiatric morbidity. But few systematic studies have addressed this issue in
      the Arab region. In this study, we investigated the help-seeking preferences for
      mental health problems in a community sample. 325 parents contacted as part of a
      community-based study of child psychiatric disorders were surveyed using a
      semistructured interview schedule. Only 38% of those surveyed indicated they
      would seek help from mental health specialists in the event of psychiatric
      problems developing in a family member, including their children. Main reasons
      given for nonconsultation were reluctance to acknowledge that a member of their
      family has a mental illness, stigma attached to attending mental health services,
      and the skepticism about the usefulness of mental health services. Willingness to
      utilize psychiatric services was associated with better parental education,
      occupation, and socioeconomic status. Our results suggest that sociocultural
      factors and parental perceptions may have a major effect on whether children with
      psychiatric disturbance receive professional help.

PMID- 15154200
TI  - Three-year outcomes of exposure to a science curriculum.
AB  - From 1,142 seventh and eighth graders responses to paper-and-pencil measures were
      correlated with scores on a science-based antismoking curriculum and on tobacco
      use behavior (-.14 to -.24).

PMID- 15154201
TI  - Analyzing the aesthetic impressions of alexithymic Japanese students.
AB  - We investigated the association between alexithymic tendencies as measured by the
      20-item Toronto Alexithymia Scale and the characteristics of aesthetic
      impressions for words and drawings. Impressions were measured using the semantic
      differential technique in three groups of Japanese students (High scores n = 31,
      Moderate scores n = 40, and a Control group n = 182) who were presented only
      words (Word condition), only drawings (Drawing condition), or pairs comprising
      one word plus one drawing that represented the same emotional categories
      (Drawing/Word condition). In a factor analysis on the data from participants,
      three factors (Evaluation, Activity, and Potency) were extracted. Based on the
      factor scores, the distances among the three conditions were calculated for each
      of the groups. For Potency, significant group differences were found between the
      Drawing/Word and other conditions. In the High-scoring alexithymia group, in
      particular, the Potency impressions based on tactile sensation, e.g., soft-hard,
      blunt-sharp, were amplified regardless of stimulus condition. These results are
      discussed in the context of somatosensory amplification associated with
      alexithymia and the difficulty of distinguishing between emotion and somatic
      sensations.

PMID- 15154202
TI  - Effects of preshift small magnitude of reward received during goalbox placements
      on the negative contrast effect.
AB  - During preshift, one experimental group of rats was given a large magnitude of
      food reward following a traversal of a straight alley and during a goalbox
      placement, while the other experimental group was given a small reward during
      goalbox placement and a large reward following a run. During postshift, all
      experimental groups were given a small reward of food following a traversal down
      the runway and during a goalbox placement. A control group was maintained on
      small reward during placements and following a traversal throughout the study.
      Only the group who received preshift large reward during placement and following
      a runway response ran slower to small reward during postshift than the control
      group maintained on small reward (negative contrast effect).

PMID- 15154203
TI  - Comparison of scores for abused and nonabused young adults on the Psychological
      Trauma and Resources Scale.
AB  - The Psychological Trauma and Psychological Resources Scale has been developed to
      identify adolescents and adults who have experienced traumatic events, i.e.,
      physical, sexual, or emotional abuse and neglect. The scale also attempts to
      identify the presence of compensatory or resource factors such as social support
      that may serve to ameliorate the effects of traumatic events. 98 college
      participants who reported a history of abuse were compared with 464 nonabused
      students on the seven subscales. As predicted, the abused participants reported
      significantly more incidents of abuse and neglect than the nontraumatized group.
      In addition, the abused group reported receiving less emotional support, and they
      were less likely to use positive self-talk as a way to decrease emotional
      distress. These results provide empirical support for using the Psychological
      Trauma and Psychological Resources Scale to identify individuals with a history
      of abuse. Findings underscore the importance of assessing resource variables that
      may moderate the effects of abuse.

PMID- 15154204
TI  - Career decision-making self-efficacy of South African high school boys and girls.
AB  - Social cognitive career theory suggests that males and females may not differ in
      career decision-making self-efficacy, but this statement requires extension of
      research to high school samples. The Career Decision-making Self-efficacy Scale
      Short Form was administered to white South African high school students in Grades
      9 to 11, of whom 368 were boys and 494 girls. No significant sex differences were
      found, suggesting that career interventions based on social cognitive career
      theory in high school need not be sex-specific in content.

PMID- 15154205
TI  - Contributions of thinking styles to vocational purpose beyond self-rated
      abilities.
AB  - The present study predicted vocational purpose from thinking styles, a construct
      at the interface of intelligence and personality. 233 students majoring in
      history and computer science from a large research-oriented university in the
      People's Republic of China completed the Thinking Styles Inventory and the Iowa
      Vocational Purpose Inventory. The participants also rated their own analytical,
      creative, and practical abilities. In general, results indicated that thinking
      styles contributed to vocational purpose beyond self-rated abilities.
      Specifically, the more creativity-generating and complex thinking styles tended
      to contribute positively to vocational purpose, whereas the more conforming and
      simplistic thinking styles tended to contribute negatively to vocational purpose.
      This article points to the need theoretically for integrating the construct of
      thinking style into the definition of differential psychology. Practical data
      argue for a collaborative working relationship between teachers and vocational
      counselors in institutions of higher education.

PMID- 15154206
TI  - Task performance and metacognitive experiences in problem-solving.
AB  - The effects of task performance on metacognitive experiences and relations
      between task performance and metacognitive experiences in problem-solving were
      examined with 69 Japanese undergraduate students. The task was a puzzle called
      the cross breaker, consisting of seven pieces, and several figures were
      constructed by using those seven pieces. Eight types of metacognitive
      experiences, before and after performing the task, were rated. Participants were
      classified into Success and Failure groups based on their task performance. Use
      of all but two metacognitive experiences differed between the groups. There were
      medium to high positive and negative correlations for metacognitive experiences
      with performance after the puzzle task, whereas metacognitive experiences before
      the task generally had no significant correlations with performance. Despite
      small N, participants' metacognitive experiences seemed to reflect their actual
      performance, suggesting that people obtain information from their performance and
      use it to revise their metacognitive experiences. Furthermore, metacognitive
      experiences may help people solve similar problems in the future.

PMID- 15154207
TI  - Rates of homicide and suicide on major national holidays.
AB  - Rates of U.S. homicides and suicides during 1972-1979 were higher on 7 major
      national holidays except one for homicides and were lower for suicides, except
      New Year's Day as Lester noted for 1972-1979.

PMID- 15154208
TI  - Test-retest reliability of the Mirowsky-Ross 2 x 2 Index of the Sense of Control.
AB  - This study investigated the short-term stability of the 1991 Mirowsky-Ross 2 x 2
      Index of the Sense of Control. From an ongoing longitudinal study, 304 subjects
      were randomly selected for test-retest interviews occurring 1 to 4 days after
      their regularly scheduled first follow-up interview. Test-retest reliability was
      assessed at the item level using percent agreement and weighted kappa. At the
      scale score level, reliability was assessed with the intraclass correlation
      coefficient (ICC). ICCs were also calculated within categories of demographic,
      socioeconomic, psychosocial, and functional status characteristics. There was
      moderate to substantial item-level agreement (mean weighted kappa = 51; weighted
      kappa range = .38 to .66). At the scale score level there was substantial
      agreement (ICC = .71). No appreciable differences in ICC values were found in the
      demographic, socioeconomic, psychosocial, and functional comparisons of status
      characteristics. Thus, this sense of control measure has acceptable test-retest
      reliability and is appropriate for use in longitudinal research.

PMID- 15154209
TI  - Self-defeating personality and memories of parents' child-rearing behavior: a
      replication.
AB  - A recent study of correlations of self-defeating personality and memories of
      parents' child-rearing behaviour has been replicated on a larger sample. Non
      clinical volunteers (145 women and 114 men) were administered Schill's Self
      defeating Personality Scale and a short version of the EMBU-Egna Minnen
      Betraffande Uppfostran (own memories of parental education) scale. Replicating
      previous findings, memories of rejecting or nonsupportive parents were
      significantly correlated with scores for the Self-defeating Personality Scale for
      both women (rejecting mother, r = 24; supportive mother, r = -.29; rejecting
      father, r = .23; supportive father, r = -.36) and men (rejecting mother, r = 40;
      rejecting father, r = .41; supportive father, r = -.28). Memories of an
      overinvolved parent were significantly correlated with self-defeating personality
      scores only among men (mother: r = .41; father: r = .36) as in the original
      study.

PMID- 15154210
TI  - Myers-Briggs personality types of art collectors.
AB  - 27 art collectors (13 men, 14 women) completed the Myers-Briggs Type Indicator.
      Their age range was 37 to 86 years and the mean 59.5 yr. Seventy percent were
      classified as Intuition types instead of Sensation types (versus its 25%
      incidence in the general population). This corresponds to personality profiles of
      artists and the disproportionately high incidence of high scores on the related
      Openness to Experience factor in studies of creative personalities, thereby
      supporting the contention that persons creating art and appreciating art have
      personality traits in common.

PMID- 15154211
TI  - Teaching safety skills to children to prevent gun play.
AB  - Research has shown that children often engage in gun play when they find a
      firearm and that this behavior is often involved in unintentional firearm
      injuries. Previous research has shown existing programs to be ineffective for
      teaching children safety skills to reduce gun play. This study examined the
      effectiveness of a behavioral skills training (BST) program supplemented with in
      situ training for teaching children safety skills to use when they find a gun
      (i.e., don't touch, leave the area, tell an adult). Eight 4- to 5-year-old
      children were trained and assessed in a naturalistic setting and in a generalized
      setting in a multiple baseline across subjects design. Results showed that 3 of
      the children performed the skills after receiving BST, whereas 5 of the children
      required supplemental in situ training. All children in the study learned to
      perform the skills when assessed in a naturalistic setting and when assessed in a
      generalization setting. Performance was maintained at 2- to 8-week follow-up
      assessments.

PMID- 15154212
TI  - A rapid assessment of skills in young children with autism.
AB  - Educational interventions based on the principles of behavior analysis are highly
      effective for establishing skills in young children with autism. As a first step
      in program development, the child's current skill level is determined by
      evaluating performance on tasks drawn from a preestablished curriculum. However,
      few specific guidelines have been delineated for conducting these skills
      assessments or interpreting the results. In this study, we evaluated an efficient
      methodology for conducting skills assessments. Six children who had been
      diagnosed with autism participated. The relative efficacy of two assessment
      packages--one containing several reinforcement procedures and one containing
      several potentially effective prompts--was evaluated across two to three skills
      for each child using multiple baseline and reversal designs. Results suggested
      that the methodology was useful for matching targeted skills to appropriate
      interventions.

PMID- 15154213
TI  - On the relative contributions of noncontingent reinforcement and escape
      extinction in the treatment of food refusal.
AB  - In the current investigation, we evaluated the relative effects of noncontingent
      reinforcement (NCR), escape extinction, and a combination of NCR and escape
      extinction as treatment for the feeding problems exhibited by 4 children. For
      each participant, consumption increased only when escape extinction was
      implemented, independent of whether NCR was present or absent. These results were
      consistent with prior research suggesting that positive reinforcement alone is
      insufficient for increasing consumption, and that escape extinction often is
      necessary to increase and maintain food acceptance. However, NCR appeared to
      decrease inappropriate behavior for some participants.

PMID- 15154214
TI  - Generalization in a child's oppositional behavior across home and school
      settings.
AB  - A 9-year-old clinic-referred boy, his mother, and his teacher were observed in 38
      home and 38 school sessions on the same days. Categories of the boy's
      oppositional behavior and the inappropriate social attention of his mother and
      teacher were graphed to visually inspect changes during baseline, a parent
      training phase, a follow-up phase, and a final parent-training booster phase.
      Parent-training phases produced reductions in the mother's inappropriate
      attention and in the boy's oppositional behavior, whereas the follow-up and
      baseline phases were associated with higher rates of these categories.
      Generalization occurred in the school across these home phases, as seen in the
      increase in rates of the boy's problem behavior, despite the lack of change in
      his teacher's attention. Correlational analyses of proportion scores reflecting
      the boy's home-school oppositional behavior and mother-teacher social attention
      suggested his responsiveness to relative changes in adult social contingencies
      across settings.

PMID- 15154215
TI  - Effects of task difficulty and type of contingency on students' allocation of
      responding to math worksheets.
AB  - This study investigated students' allocation of responding as a function of task
      difficulty and type of reinforcement contingency (i.e., accuracy based or time
      based). Four regular education fourth-grade students were presented with two
      identical stacks of easy and then difficult math worksheets using a reversal
      design. Regardless of condition, completing problems from each stack of
      worksheets was reinforced according to a different contingency; one required
      correct completion of math problems (accuracy based) and one required on-task
      behavior (time based). Results suggested that 3 of the 4 students preferred the
      accuracy-based contingency when given easy material and the time-based
      contingency when given difficult material. One student allocated more responding
      to the accuracy-based contingency when given easy problems but did not show a
      clear preference for either contingency with difficult problems. The implications
      of these findings for designing reinforcement-based programs for tasks of varying
      difficulty are discussed.

PMID- 15154216
TI  - Applications of computer-based instruction: using specialized software to aid
      letter-name and letter-sound recognition.
AB  - We evaluated computerized training and testing programs with children who were
      having difficulties learning prereading skills. The programs were derived from
      equivalence research and were written in authoring software designed for
      educators. After learning to match uppercase and lowercase printed letters to the
      corresponding letter names (Tasks 1 and 2), the children matched the letters to
      one another (Tasks 4 and 5). Then, after learning to match uppercase letters to
      sounds (Task 3), they also matched lowercase letters to sounds (Task 6) and
      matched printed to spoken words (Tasks 7 and 8). The results recommend
      equivalence-based protocols and user-friendly software in further development of
      prereading instruction.

PMID- 15154217
TI  - Systematic application and removal of protective equipment in the assessment of
      multiple topographies of self-injury.
AB  - We evaluated the effects of systematic application and removal of protective
      equipment on three topographies of self-injurious behavior (SIB) exhibited by a
      girl who had been diagnosed with autism. Results showed that when protective
      equipment was applied, SIB decreased to near-zero levels. In addition, withdrawal
      of protective equipment for specific topographies of SIB (by removing only the
      corresponding padding) increased rates of SIB only for that topography of SIB.
      Next, a functional analysis of hand SIB showed that protective equipment
      suppressed this behavior in all conditions and that the behavior was maintained
      by automatic reinforcement when padding was removed. Results are discussed in
      terms of sensory extinction as a possible mechanism responsible for response
      suppression.

PMID- 15154218
TI  - Teaching teenagers with autism to seek assistance when lost.
AB  - Three teenagers with autism were taught to respond to a vibrating pager to seek
      assistance in community settings when physically separated from their parents or
      teachers. A multiple baseline probe design across participants demonstrated that,
      upon being paged, participants successfully handed a communication card to a
      community member indicating that they were lost. Generalization was assessed in
      nontraining community sites and on outings with the participants' parents.

PMID- 15154219
TI  - An evaluation of response cost in the treatment of inappropriate vocalizations
      maintained by automatic reinforcement.
AB  - In the current study, we examined the utility of a procedure consisting of
      noncontingent reinforcement with and without response cost in the treatment of
      inappropriate vocalizations maintained by automatic reinforcement. Results are
      discussed in terms of examining the variables that contribute to the
      effectiveness of response cost as treatment for problem behavior maintained by
      automatic reinforcement.

PMID- 15154220
TI  - Training educators to implement functional analyses.
AB  - The present study examined the use of an instructional workshop for training
      educators to conduct functional analyses. Results indicated that 2 of 3
      participants met the accuracy criterion following group training, whereas 1
      participant required direct verbal feedback. During generalization probes, one
      participant accurately conducted sessions with a student in her classroom.

PMID- 15154221
TI  - Effects of video modeling on social initiations by children with autism.
AB  - We examined the effects of a video modeling intervention on social initiation and
      play behaviors with 3 children with autism using a multiple baseline across
      subjects design. Each child watched a videotape showing a typically developing
      peer, and the experimenter engaged in a simple social interactive play using one
      toy. For all children, social initiation and reciprocal play skills were
      enhanced, and these effects were maintained at 1- and 3-month follow-up periods.

PMID- 15154222
TI  - Extended diaper wearing: effects on continence in and out of the diaper.
AB  - Diaper use is widespread and possibly even increasing across diverse populations
      in the United States, ranging from infants to very old adults. We found no
      reports of an experimental analysis of the effect of wearing diapers on the
      frequency of urinary accidents and the attainment of continence skills (e.g.,
      urinating in the toilet). In this study, we used a withdrawal design to evaluate
      the effect of wearing diapers on daily urinary accidents and successful voids for
      an adult who had been diagnosed with mental retardation. Results indicated that
      wearing diapers increased the rate of accidents and decreased the rate of
      successful voids. Clinical implications of these results are discussed.

PMID- 15154223
TI  - Preference for progressive delays and concurrent physical therapy exercise in an
      adult with acquired brain injury.
AB  - The purpose of this study was to increase self-control and engagement in a
      physical therapy task (head holding) for a man with acquired traumatic brain
      injury. Once impulsivity was observed (i.e., repeated impulsive choices), an
      experimental condition was introduced that consisted of choices between a small
      immediate reinforcer, a large fixed-delay reinforcer, and a large progressive
      delay reinforcer. The participant showed a preference for the progressive-delay
      option, even when the duration of the delay exceeded that of the fixed delay. The
      results have implications for establishing optimal choice making and teaching
      life-enhancing skills.

PMID- 15154224
TI  - Decreasing entry into a restricted area using a visual barrier.
AB  - Wandering is a difficult-to-manage behavior problem for individuals with
      cognitive impairments that can jeopardize safety if an individual enters a
      hazardous area or becomes lost. This study investigated the effects of a cloth
      barrier on entry into an unsafe area. The cloth barrier reduced entry into the
      restricted area and had high treatment acceptability.

PMID- 15154225
TI  - An experimental analysis of reading interventions: generalization across
      instructional strategies, time, and passages.
AB  - This study examined the generalized effects of three treatment conditions
      (performance based, skill based, and a combination of the two) on oral reading
      fluency by an elementary school student. Results indicated equal effectiveness of
      all treatments, maintenance, and possible evidence of generalization across
      passages.

PMID- 15154227
TI  - [Progressive decrease of the causes that maintain ventricular fibrillation after
      experimental coronary occlusion].
AB  - Progressive diminution of the causes that maintain ventricular fibrillation after
      coronary occlusion. Extracorporeal circulation was performed on a group of normal
      dogs in which a ligature was placed on the left anterior descending coronary
      artery, immediately beneath the bifurcation of the left coronary artery. The
      incidence of ventricular fibrillation was of 15 dogs out of 20 (table 1). In a
      control group without extracorporeal circulation ventricular fibrillation
      appeared in 24 dogs out of 30 (table 2). These results demonstrate that
      extracorporeal circulation performed with the idea of improving coronary
      circulation does not prevent ventricular fibrillation in coronary occlusion. In
      those dogs with the cross circulation, attempts to defibrillate the ventricles
      with an electric a.c. defibrillator (three electrical shocks applied directly on
      the myocardium every 4 or 5 minutes) were uniformly unsuccessful until a period
      ranging from 12 to 80 minutes elapsed after the onset of ventricular
      fibrillation. After these periods all fibrillating dogs were defibrillated and
      recovered either normal or idioventricular rhythm. It is assumed that a
      "fibrillator substance" liberated by the injury in the initial state of
      infarction is washed out of the myocardium, or a zone of increased excitability
      and conduction disturbance is progressively eliminated so that the chances of
      originating circus movements are diminished.

PMID- 15154226
TI  - Creating activity schedules using Microsoft Powerpoint.
AB  - We describe how PowerPoint presentation software can be used to create computer
      activity schedules to teach individuals with special needs. Presented are the
      steps involved in creating activity schedules with close-ended and open-ended
      activities, and for preparing schedules that include photos, sounds, text, and
      videos that can be used to occasion an individual's engagement in a variety of
      learning activities.

PMID- 15154228
TI  - [Study of PBI 131 urinary elimination and collection located in breast carcinoma
      with or without metastasis].
AB  - In 9 female patients with breast cancer, we studied the diagnostic uptake of I131
      at 24 hours, localization of I131 in the thyroid, primary breast tumor and its
      metastases, urinary excretion of I131 at 24 hours and PBI131, and came to the
      following conclusions: 1. Low normal values for uptake at 24 hours was observed
      as in previous studies. 2. There was no I131 uptake in the primary breast tumor
      or its metastases. 3. The sum of 24 hour uptake levels plus the urinary excretion
      at 24 hours were within normal limits. 4. Therefore, the relatively low uptake
      figures, which were repeatedly observed in these patients, are not due to
      competition between the thyroid uptake of I131 and the neoplastic tissue.

PMID- 15154229
TI  - [Comparison between the bacterial flora airways and of the lung tissue].
AB  - In 44 patients tracheotomized and under mechanical ventilation bacteriological
      studies were carried out, inmediately after death, in bronchial secretions and in
      a small piece of lung obtained by thoracotomy. The more frequently found
      bacterium in bronchial secretions or the lung was the Pseudomona aeruginosa
      (Table 1). In order of decreasing frequency: Klebsiella, Staphylococcus, Proteus,
      etc. were found in the lung while in bronchial secretions the order was inverse
      by predominance of Proteus. Total bacteriological coincidence was found in 14
      cases while it was partial in 8 more patients where another bacterium was added
      in bronchial secretions. Bacteria were different in 6 cases (Table 2) in 4 of
      them: staphylococcus was obtained in the lung while Pseudomonae, Proteus and
      Klebsiellae were present in bronchial secretions (Table 3). In 16 cases cultures
      of the piece of lung taken were negative. Not taking into account these last
      ones, it is possible to conclude that from the therapeutic stand point culture of
      bronchial secretions was useful in antibiotic selection in 22 out of 28 cases.

PMID- 15154230
TI  - [Immunologic phenomena in guinea pigs injected with homologous ganglia extracts].
AB  - Immunological modifications in guinea pigs injected with homologous lymph node
      extracts. In studies carried out in patients with lymphomas an accentuation of
      the B2M-globulin line was observed; occasionally paraproteins and isoantibodies
      were detected. For this reason the authors decided to find out whether the
      injection of homologous lymph node extracts in guinea pigs would produce serum,
      immunological and histological modifications comparable to the ones observed in
      the human being. A total of 100 guinea pigs were divided into 4 groups. Group 1,
      50 untrated control animals; Group 2, 10 animals injected with complete Freunds
      adjuvant every 10 days, for 3 times, and sacrificed 7 days after the last
      injection; Group 3, 10 animals injected with the antigen prepared with the lymph
      nodes from normal guinea pigs, in the same way as the preceding group; Group 4,
      30 animals injected with the same antigens emulsionated with the adjuvant, again
      by the same method as the 2 preceding groups. The antigen was prepared with the
      lymph nodes from normal guinea pigs. The cells were "ultrasonicated" and
      lyophilized; the lipids were extracted with chloroform. The extract thus obtained
      contained an average of 2 mg/ml of total proteins. A microimmunoelectrophoretic
      study (MIE) against rabbit immuno serum for guinea pigs anti-serum proteins,
      showed that it was contaminated with various serum proteins (fig. 1, A). In the 3
      injected groups, most of the guinea pigs showed a 10% decrease in serum protein
      (Table). Using MIE there was a re-enforcement of the B2M-globulin precipitation
      line (IgM), in all the animals of groups 2 and 4, as compared to the groups 1 and
      3 (Table and figure 1. B and C). Using microdiffusion in agar, the serum of 6% of
      the guinea pigs of group 4 gave precipitation lines with the homologous antigen
      (Table, figure 1, D). Using passive hemagglutination, between 30 and 40% of the
      serum of the animals of all 4 groups gave positive results with the same antigen,
      with a low titer (1/40). Using complement fixation, positive results were
      obtained with the lymph node antigen in 10% and 20% of the animals of groups 3
      and 4 respectively: from 25 to 50% fixation with a titer of 1/10 (Table). Using
      immunofluorescence, positive images in the cytoplasm of lymphocytes (from
      improntas of normal guinea pigs lymph nodes) were obtained only in the labeled
      gamma-globulin (IgG) of the animals of group 4 (Table and figure 2, C).
      Histological study of the lymph nodes of guinea pigs from groups 2 and 4 showed
      hyperplasia of the reticular tissue with apparent decrease in the size of the
      follicles. In some of the lymph nodes of the animals of group 4, giant cells were
      observed (Fig. 2, B), pironinophilic. In the group 3 hypertrophy of the lymphoid
      follicles was observed (fig. 2, A). Non-specific modifications of the serum
      proteins, similar to the ones observed in patients with lymphomas were detected
      in some of the animals belonging to groups 2 and 3 in a greater number of animals
      in group 4. Circulating isoantibodies could be compared to those detected in 2
      cases of lymphosarcoma. In spite of definite histological alterations of the
      lymphatic organs, these cannot be compared with the alterations detected in the
      human being.

PMID- 15154232
TI  - [Clinical and phonocardiographic considerations about ejection sound].
AB  - The clinical data of 38 patients in whom an added sound at the beginning of the
      ejection phase was demonstrated in the phonocardiogram, are reviewed and compared
      with the x-ray picture, the electrocardiogram and in 7 cases with hemodynamic
      studies. In 28 of these patients, the systolic click was more intense at the apex
      or at the aortic area, while in the other 10 cases, it was more easily detected
      at the pulmonary area. In the first group we found 13 patients with aortic
      insufficiency, 2 with aortic stenosis, 8 with arterial hypertension, 3 with
      marked aortic atherosclerosis, 1 cases of coartation of the aorta an 1 patient
      with aortic dilatation of unknown origin. The second group was composed by 4
      cases of mitral stenosis, 3 patients with chronic cor pulmonale, 1 with subacute
      cor pulmonale, 1 case of valvular pulmonary stenosis and 1 case of Eisenmenger's
      Syndrome with persistence of the ductus arteriosus. A feature common to all cases
      was the finding of marked dilatation of the aorta or the pulmonary artery. The
      problems in differential diagnosis with the splitting of the first heart sound
      and with the auricular sound are analyzed and the possible pathogenic mechanisms
      discussed, emphasizing the role of the dilation of the main vessels during
      ventricular ejection.

PMID- 15154231
TI  - [Anatomoclinical study of pulmonary embolism in patients with or without
      pulmonary infarction].
AB  - The autopsy protocols of 560 patients were studied in order to detect the
      incidence of pulmonary embolism, 83 cases were found (15%). The clinical data was
      analyzed to establish the existence of differentiating points between subjects
      with pulmonary infarcts and those with embolism but without infarction. The
      necropsy findings were further scrutinized to determine the effect of the
      anatomic localization of the embolus upon the production of infarction. Pulmonary
      infarctions were present in 60% of the cases with pulmonary embolus. The presence
      of cardiac failure, valvular heart disease and left ventricular hypertrophy was
      significantly more frequent in patients with pulmonary infarcts. In subjects with
      or without infarction the age, sex and the presence of medical debilitating
      diseases, recent trauma, surgical interventions or postpartum, cardiac diseases,
      arteriosclerotic heart disease, clinical evidence of thrombophlebitis, prolonged
      bed rest and atrial fibriliation preceding the pulmonary embolism, did not
      evidenciate any significant difference. In the cases with infarction the
      pulmonary embolus was significantly more frequently located in the small and
      sublobar pulmonary artery branches, while when pulmonary infarction was not found
      the embolic process was more frequently located in the main, right or left
      pulmonary arteries; occlusion of the lobar arteries had approximately the same
      incidence in the two groups. The most common clinical signs of pulmonary
      thromboembolism were dyspnea, tachycardia, cough and shock. The presence of
      hyperthermia, cough, jaundice, bloody sputum, pleuritic pain, pleural friction
      rub and pleural effusion was significantly more frequent in those cases with
      pulmonary infarction; the last five features were present only in the presence of
      infarction. The electrocardiogram was strongly suggestive of pulmonary embolism
      in the 6% of all cases, while the chest X-ray in 30% of those with pulmonary
      infarct. The diagnosis was established antemortem in 40% of the cases with
      infarction and in 20% of the cases with embolus but without pulmonary infarction.
      In 23% adequate anticoagulant therapy was established.

PMID- 15154233
TI  - [Polycystic hepatic and renal disease with portal hypertension and ascites (a
      case report)].
AB  - The case of a 50 years old man with polycystic liver and kidneys and ascites
      which had been diagnosed by laparoscopy and pyeloureterography, is reported.
      Chronic renal failure was the cause of death, and obvious signs of portal
      hypertension were found at necropsy. The loss of hepatic structure produced by
      pericystic fibrosis, regenerative nodules, thrombosis of portal branches, and
      necrotic areas, is stressed as an important cause of portal hypertension. This
      pathogenesis could be similar to that of cirrhosis. Both portal hypertension and
      ascites are highly uncommon facts in adults' polycystic livers.

PMID- 15154234
TI  - [Culture of human peripheral lymphocytes in immunology ].

PMID- 15154235
TI  - [The scientific method in development on the doctor of the future].

PMID- 15154236
TI  - [Renal circulation in acute kidney failure].

PMID- 15154237
TI  - [Potassium depletion secondary to kidney diseases by outdated tetracyclines].

PMID- 15154238
TI  - [Causes and methods of the conversion completion in laparoscopic
      cholecystectomy].
AB  - The literature data and the authors own experience, concerning complications,
      occurring while laparoscopic cholecystectomy performance, demanding the
      conversion conduction, were analyzed. The authors make the conclusions concerning
      the conversion threshold and the ways to lower its frequency.

PMID- 15154239
TI  - [Versions of the bile outflow restoration in reconstructive and restorative
      surgery on the bile duct].
AB  - The results of performance of 90 restoration and reconstructive operations in 71
      patients with iatrogenic injury of extrahepatic biliary ducts were analyzed. The
      risk factors of iatrogenic injury were delineated. Original methods of
      restoration of the bile outflow into intestine were offered. The method of
      external extraperitoneal cholangiostomy via hepatic round ligament was
      recommended. Total postoperative mortality had constituted 15.7%.

PMID- 15154240
TI  - [Efficacy of cycloferon and erbisol in the complex surgical treatment of multiple
      gastroduodenal ulcers].
AB  - There were examined 65 patients with multiple gastroduodenal ulcers. The
      formation of secondary immune deficiency state on background of endogenic
      "methabolic" intoxication syndrome was noted in them. The blood immune indexes
      normalization was promoted by cycloferon and erbisol incorporation in complex of
      surgical treatment of multiple gastroduodenal ulcers. While conduction of the
      dispensary follow-up observation in 80% of patients the laboratory indexes have
      had persisted normal. In 20% of patients the conduction of repeated course of
      treatment, using erbisol and cycloferon, is indicated in 6-8 months after
      surgical treatment.

PMID- 15154241
TI  - [Endogenous intoxication syndrome in complicated acute cholecystitis].
AB  - The endogenous intoxication syndrome was investigated in patients, operated on
      for an acute cholecystitis, using open cholecystectomy. Peculiar attention was
      drawn to studying of the endotoxicosis severity in patients with complicated
      course of an acute cholecystitis in dynamics.

PMID- 15154242
TI  - [The performance of balloon Vater's ampulla dilatation in laparoscopic
      cholecystectomy as a method of choledocholithiasis treatment].
AB  - Experience of application of the antegrade balloon dilatation method for Vater's
      papilla sphincter during performance of laparoscopic cholecystectomy in patients
      with the gall-stone disease, complicated by choledocholithiasis, was presented.
      Short duration of hospital stay (5.5 days), low frequency of postoperative
      complications (4.5%), good late follow-up results witness the expediency of the
      method broad introduction into clinical practice.

PMID- 15154243
TI  - [Repeated intestinal exploration and multi-stage surgeries within the program of
      the treatment of segment necrosis and the small intestine ischemia].
AB  - An ischemic intestinal affection is observed frequently, its diagnosis difficult,
      mortality is high. In the clinic there were followed 47 patients with an ischemic
      intestinal affection. In 24 of them the etiology of ischemia was mesenterial
      thrombosis, in 23--strangulational ileus. While the doubt in intestinal viability
      existed, relaparotomy was performed for its state estimation and in necrosis
      resection with primary anastomosis conduction. Mortality was 2.1%. Application of
      such a tactic had permitted to reduce significantly the frequency of resection
      conduction while doubt in intestinal viability present as well as mortality--in
      intestinal necrosis.

PMID- 15154244
TI  - [Specifics of anesthesia in extensive liver resection].
AB  - There were analyzed the results of anesthesiological securing while performance
      of extensive hepatic resection in 46 patients (extended rite-sided--in 21, left
      sided--in 22, mesohepatectomy--in 3) with preservation of 20-40% of the organ
      volume, including preoperative preparation, analgesia and intensive therapy after
      the operation. Combined epidural anesthesy is the method of choice in extensive
      hepatic resection, she promotes the pharmacological loud reduction with narcotic
      analgetics and myorelaxants, earlier extubation and activisation of patients
      after the operation. Its combination with isofluran, circulating in closed
      contour, is perspective.

PMID- 15154245
TI  - [Revision laparotomy in patients with high surgical risk].
AB  - Results of analysis of exitus letalis in 256 patients, in 36 of whom relaparotomy
      was conducted, were adduced. There were established prognostically significant
      factors of the surgical treatment risk, which was choosed for the absence of
      alternative methods. It was established, that the main cause of mortality of
      patients in 7.2-10.9% of cases was the complicated course of the disease. The
      main diseases, in which the need for relaparotomy performance occurs, are
      gastric, colonic, rectal, hepatopancreatobiliary zone cancer, complicated gall
      stone disease. The mortality risk during performance of treatment constitutes
      6.41%. In 93.8% of patients atherosclerotic affection of cardiac coronary vessels
      was revealed, demanding conduction of the staged cardiosurgical correction. The
      direct cause of the death were cardiovascular system diseases on background of
      the principal disease progressing.

PMID- 15154246
TI  - [Application of plasmapheresis and perftoran in thoracic diseases].
AB  - In patients with purulent disease of thoracic cavity the discrete plasmapheresis
      and infusion-transfusional therapy, using perftoran emulsion, were applied in
      complex of treatment. The efficacy of application of oxygentransporting blood
      substitutes, based on perfluorohydrocarbons, for the plasmexfusion and in the
      treatment of respiratory hypoxia in patients was established.

PMID- 15154247
TI  - [Changes of thrombocyte activity and results of surgical treatment of colon
      cancer under the influence of heparins and ticlopidine].
AB  - Comparative analysis of influence of unfractionated heparin, calcium nadroparin
      and combined application of calcium nadroparin and ticlopidin on the thrombocytes
      activity was conducted. Analysis of late follow up results of treatment witnessed
      that using various diagrams of antithrombotic therapy in patients with colonic
      cancer the indexes of cumulative survival are different.

PMID- 15154248
TI  - [Preliminary results of lymphatic chemotherapy in the treatment of rectal
      cancer].
AB  - Preliminary results of treatment of 28 patients with cancer recti, in whom
      lymphatic chemotherapy was applied and operative intervention as well, were
      studied. The results of treatment in control group, consisting of 28 patients, to
      whom neoadjuvant systemic chemotherapy was conducted, are adduced. Comparative
      analysis performed have shown that general toxic signs occurred three times
      lesser in patients of the main group, than in a control one; the postoperative
      complications was two times lesser. In one-year follow-up in the main group the
      recurrences and metastases were absent, in a control group the tumor recurrence
      had occurred in 3 (10%) of patients.

PMID- 15154249
TI  - [Analysis of the results in pheochromoblastoma treatment].
AB  - Results of operative treatment of 60 patients with pheochromoblastoma were
      analyzed. Surgical method of treatment is the most effective one. Lumbotomic
      extraperitoneal access is the method of choice. Oncological radicalism demands
      not only complete excision of primary tumor in sole capsule together with
      suprarenal gland, but also the revision of paranephral, paracaval and paraaortal
      cellule. Radical intervention with subsequent durable remission was performed in
      38 (63.3%) of patients, also in 3 (5%) the remission was achieved after
      reintervention conduction. Two (3.3%) patients are living with persisting
      disease, which can be controlled easier using medicines, than before the
      operation. In 8 (13.3%) patients with the spread metastases revealed and they
      were directed to symptomatic therapy by their residence. The recurrence
      occurrence after primary operation performance is unfavorable prognostic feature:
      55.8% of such patients were considered incurable. Operative treatment performed
      had guaranteed the disease remission achievement in 71.9% of patients.

PMID- 15154250
TI  - [Application of auto-pericardium for closure of the pulmonary artery defect].
AB  - In 7 patients with the pulmonary artery thromboembolism the integrity of the
      pulmonary artery its branches were restored using the patch made of
      autopericardium sewing in. The author recommend to use the methods for the
      pulmonary artery restoration in operative intervention performed on her.

PMID- 15154251
TI  - [Varicose disease: classification and ultrasonic diagnosis].
AB  - Results of clinical examination and ultrasonic investigation in 478 patients with
      varicosic disease (VD) of lower extremities are adduced. Basing on the data
      obtained the clinicoanatomic forms of VD were deliniated. The typical and
      nontypical forms diseases criterions of ultrasound diagnosis were determined. It
      was demonstrated that the choice of the surgical treatment tactics in patients
      with VD depends on its clinicoanatomic form, and the principal method of
      diagnosis is the color duplex scanning.

PMID- 15154252
TI  - [Superior vena cava patency syndrome in a patient with chronic mediastinal
      compression].
AB  - There are adduced the literature data and own observation of rare disease of main
      thoracic cavity veins-syndrome of disorder passability of vena cava superior
      (SDPVCS). The most frequent causes of SDPVCS occurrence, informative methods of
      diagnosis, mane methods of treatment were enlighted.

PMID- 15154253
TI  - [What is the diagnosis of "diabetic foot syndrome"? The evolution of opinions on
      the problem and possible ways of its solution. In summarizing the 2nd Plenary
      meeting of the Vascular Surgeon Association of the Ukraine, April 29-30, 2003].

PMID- 15154254
TI  - [Isolated echinococcal pancreatic lesions].

PMID- 15154255
TI  - [Diagnosis and treatment of the contact odontogenic mediastinitis].

PMID- 15154256
TI  - Integrative science: a modeling challenge.

PMID- 15154257
TI  - The many facets of homeland security.

PMID- 15154258
TI  - Technology and policy review for homeland security.

PMID- 15154259
TI  - Quality of life impact of public policies for energy and telecommunications.

PMID- 15154260
TI  - A biointelligence system for identifying potential disease outbreaks.

PMID- 15154262
TI  - Building a semantic Web for securing the homeland.

PMID- 15154261
TI  - Setting standards for improved syndromic surveillance.

PMID- 15154263
TI  - The case for integrating public health informatics networks.

PMID- 15154264
TI  - Transforming medicine for biodefense and healthcare delivery.

PMID- 15154265
TI  - Optimizing active and passive countermeasures.

PMID- 15154266
TI  - Information assurance in biomedical informatics systems.

PMID- 15154267
TI  - Technological challenges in counter bioterrorism.

PMID- 15154268
TI  - Real-time detection of microbial contamination.

PMID- 15154269
TI  - A second-generation anthrax "smoke detector".

PMID- 15154270
TI  - Microbiological threats to homeland security.

PMID- 15154271
TI  - The psychology of countering terrorism with technology.

PMID- 15154272
TI  - The terror part of terrorism.

PMID- 15154273
TI  - Managing the community response to bioterrorist threats.

PMID- 15154274
TI  - Conflicts of values and biodefense measures.

PMID- 15154275
TI  - Biomedical engineering's contribution to defending the homeland.

PMID- 15154276
TI  - The impact of instability in Latin and South America.

PMID- 15154277
TI  - That nefarious word, "somehow".

PMID- 15154278
TI  - The small heart and the critical mass for ventricular fibrillation.

PMID- 15154279
TI  - U.S. medical device classification.

PMID- 15154280
TI  - Ephedra-containing dietary supplements in the US versus ephedra as a Chinese
      medicine.
AB  - Ephedra has been commonly used in traditional Chinese medicine (TCM) without
      significant adverse effects. Ephedra-containing dietary supplements are widely
      used in the United States to promote weight reduction and energy enhancement.
      However, there are significant safety concerns regarding the use of ephedra
      containing dietary supplements, especially when such use occurs by consumers
      without medical supervision. This article reviews and contrasts the usage of
      ephedra as a dietary supplement in the US against an herbal medication in TCM.
      The potential adverse effects of ephedra-containing dietary supplements are also
      reviewed.

PMID- 15154281
TI  - Osthole improves aspects of spatial performance in ovariectomized rats.
AB  - The present study was designed to investigate the ameliorating effects of
      Cnidiuim monnieri L. Cusson (CM) and osthole, a constituent of CM, on the spatial
      performance deficit in scopolamine (SCOP)-treated or ovariectomized (OVA) rats.
      CM improved the deficit of spatial performance, and reversed the lower plasma
      estradiol levels caused by SCOP in female rats. In addition, osthole (3 and 10
      mg/kg, s.c.) improved the performance deficit in OVA rats. It (10 and 30
      micrograms/brain, icv) also improved the performance deficit caused by SCOP in
      intact female rats, and at 30 micrograms/brain improved the deficit in OVA rats.
      However, osthole did not alter the latency swum to reach the visible target in
      SCOP-treated and OVA rats. Accordingly, we suggested that osthole is an active
      constituent of CM, and possesses ameliorating effects on the spatial performance
      deficits in SCOP-treated female rats or OVA rats. The action mechanism of the
      effects of osthole on performance deficits was related to the estrogen-like
      properties and activating the central cholinergic neuronal system.

PMID- 15154282
TI  - The effect of Ginkgo biloba extract (EGb 761) on hepatic sinusoidal endothelial
      cells and hepatic microcirculation in CCl4 rats.
AB  - It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and
      cerebral blood flow and microcirculation and improves myocardial ischemia
      reperfusion injury. This study was designed to investigate the effect of EGb 761
      on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats
      were divided into normal, carbon tetrachloride (CCl4) and EGb groups, and were
      given normal saline, CCl4 and CCl4 plus EGb 761, respectively, for 10 weeks.
      Samples were taken from the medial lobe of the rat livers ten weeks later.
      Hepatic sinusoidal endothelial cells and other parameters of hepatic
      microcirculation were observed under transmission electron microscopy (TEM). The
      amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor
      (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry
      and radioimmunoassay, respectively. Compared with the CCl4 group, aggregation of
      blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in
      hepatic sinusoids and space of Disse, injury of endothelial cells and
      capillization of hepatic sinusoid was significantly reduced in the EGb group. The
      amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the
      CCl4 group, while no significant difference in the amount of NO was observed
      between the two groups. The results demonstrate that EGb 761 has protective
      effect on hepatic endothelial cells and hepatic microcirculation in rats with
      chronic liver injury induced by CCl4. The mechanisms may involve its inhibition
      on ET-1, PAF and lipid peroxidation.

PMID- 15154283
TI  - Production of monoclonal antibody against ginkgolic acids in Ginkgo biloba Linn.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) for ginkgolic acids (GAs)
      was developed using monoclonal antibody (MAb) 9F raised against 6-(13
      formylheptyl) salicylic acid covalently coupled to bovine serum albumin (BSA).
      ELISA, at an effective measuring range of 300 ng/ml-1 microgram/ml of GA15:1, was
      successful in detecting GAs content in ginkgo leaves and standardized extracts
      due to the lack of cross-reactivity against various related compounds. The
      sensitive and simple immunoassay developed in this study was validated to be
      specific for the quantitative determination of total GAs content in ginkgo crude
      drugs with no interference from the sample matrix. The analytical recovery of
      spiked GA15:1 was 103% in a concentration range between 10 and 40 mg/g dry weight
      of ginkgo leaves.

PMID- 15154284
TI  - The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats.
AB  - The pathogenesis of gentamicin (GM) nephrotoxicity has been shown to involve the
      generation of oxygen free radicals, and several free radical scavengers have been
      shown to ameliorate the nephrotoxicity. The seeds and oil of Nigella sativa are
      reported to possess strong antioxidant properties and was effective against
      disease and chemically-induced hepatotoxicity and nephrotoxicity. Therefore, in
      the present work, we have tested whether oral treatment of rats with N. sativa
      oil (0.5, 1.0 or 2.0 ml/kg/day for 10 days) would ameliorate nephrotoxicity of GM
      (80 mg/kg/day given intramuscularly and concomitantly with the oil during the
      last 6 days of treatment). Nephrotoxicity was evaluated histopathologically with
      a light microscope and by measurement of concentrations of urea, creatinine and
      total antioxidant status (TAS) in plasma and reduced glutathione (GSH) and TAS in
      kidney cortex. The results indicated that GM treatment caused moderate proximal
      tubular damage, significantly increased the concentrations of creatinine and
      urea, and decreased that of TAS and GSH. Treatment with N. sativa oil produced a
      dose-dependent amelioration of the biochemical and histological indices of GM
      nephrotoxicity that was statistically significant at the two higher doses used.
      Compared to controls, treatments of rats with N. sativa did not cause any overt
      toxicity, and it increased GSH and TAS concentrations in renal cortex and
      enhanced growth. The results suggest that N. sativa may be useful in ameliorating
      signs of GM nephrotoxicity in rats, and pending further experimentation to
      determine safety and efficacy, may be useful clinically.

PMID- 15154285
TI  - Hypolipidemic effect of Glycine tomentella root extract in hamsters.
AB  - The influence of the aqueous crude extract of Glycine tomentella root
      (Leguminosae) on lipid metabolism was investigated in hyperlipidemic hamsters. It
      was found that the administration of the G. tomentella extract (GTE) leads to a
      decrease of high serum cholesterol and triglyceride levels induced by high-fat
      diet. The GTE also increased serum high-density lipoprotein (HDL) cholesterol and
      decreased serum low-density lipoprotein (LDL) cholesterol. The reduction of serum
      triglyceride levels was accompanied by a significant decrease in the hepatic
      triglyceride content, while the cholesterol content was not changed. The results
      indicate that GTE is definitely an anti-hyperlipidemic agent, at least, in
      animals.

PMID- 15154286
TI  - Inhibitory effect of Spirodela polyrhixa on the secretion of NO in LPS-stimulated
      macrophages.
AB  - Spirodela polyrhixa Schleid has been used in folk medicine to treat inflammatory
      diseases. Since nitric oxide (NO) is one of the major inflammatory parameters, we
      studied the effect of aqueous extracts of Spirodela polyrhixa (AESP) on NO
      production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages.
      AESP inhibited the secretion of NO in macrophages, without affecting cell
      viability. The protein level of inducible nitric oxide synthase (iNOS) in
      peritoneal macrophages was also decreased by AESP. Transient transfection assay
      of reporter plasmid and gel shift assay indicated that AESP blocked the
      activation of nuclear factor-kappa B (NF-kappa B), which was considered to be a
      potential transcription factor for iNOS expression. AESP also blocked the
      phosphorylation and degradation of inhibitory protein I kappa B-alpha (I kappa B
      alpha). These results suggest that AESP could exert its anti-inflammatory actions
      by suppressing the synthesis of NO through inhibition of NF-kappa B activity.

PMID- 15154287
TI  - Intraperitoneal injection of ginseng extract enhances both immunoglobulin and
      cytokine production in mice.
AB  - Ginseng is one of the most widely used Chinese herbal medicines. In this report,
      the relatively short-term effect of ginseng extract on the immunoglobulin
      production and cytokine production was studied. The ginseng extract was prepared
      by boiling the ground ginseng root in 50% ethanol. The specific pathogen-free
      mice were intraperitoneally (i.p.) injected with various doses of ginseng extract
      for 3 consecutive days. The results indicated that the serum levels of
      immunoglobulin (Ig)M, IgG and IgA were significantly elevated after the mice were
      i.p. injected with 4 g/kg/day of ginseng extract. Under in vitro condition, the
      lipopolysaccharide (LPS)-stimulated spleen cells showed a dose-dependent increase
      in secretion of IgM, IgG and IgA. However, at a higher dosage (4 g/kg/day), the
      amount of IgA secretion began to decline. The serum level of interleukin (IL)-2,
      interferon (IFN)-gamma[T-helper (Th) 1-type cytokines] and IL-4 and IL-10 (Th2
      type cytokines) were significantly elevated after the mice were i.p. injected
      with 2 g/kg/day or higher doses of ginseng extract. The amount of cytokine
      secretion by concanavalin A (Con A)-stimulated spleen cells was also
      significantly enhanced after the mice were i.p. injected with 0.4 g/kg/day or
      higher dose of ginseng extracted. To further confirm the results from enzyme
      linked immunosorbent assay (ELISA), the spleen cells were cultured for 36 hours
      in the presence of 1 microgram/ml of Con A. Total mRNA was isolated and assayed
      for mRNA expression using reverse transcriptase-polymerase chain reaction (RT
      PCR). The results revealed that expression of IL-2 and IFN-gamma mRNA were dose
      dependently enhanced by the ethanol extract of ginseng. The levels of IL-4 and IL
      10 mRNA expression were also elevated in the spleen cells of ginseng-treated mice
      in comparison with that of the control group. In addition, we observed that the
      concentrations of IgG1, IgG2a and IgG2b in culture supernatants of spleen cells
      were dose-dependently increased by in vivo treatment of ginseng extract,
      suggesting that both Th1- and Th2-type cytokines were involved in IgG production.
      Our observation in this study demonstrated that the Chinese herbal drug ginseng
      was able to regulate antibody production by augmenting Th1- (IL-2, IFN-gamma) and
      Th2-type (IL-4, IL-10) cytokine production.

PMID- 15154288
TI  - Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on
      scavenging reactive oxygen species in vitro.
AB  - Scutellaria baicalensis (SbE) is a commonly used Chinese herb medicine and grape
      seed proanthocyanidins is a popular herbal supplement in the United States. Both
      herbs have been shown to possess potent antioxidant effects. Using an in vitro
      model to produce the reactive oxygen species (ROS) generation (H2O2/FeSO4 for
      hydroxyl radicals, xanthine/xanthine oxidase for suproxide), we observed that
      Scutellaria baicalensis and grape seed proanthocyanidins acted synergistically to
      scavenge ROS. Our data suggest that a combination of these two herbs can
      potentially enhance their antioxidant efficacy, allowing lower dosages of each
      drug to be used. This has the advantage of avoiding possible side effects that
      may arise when higher doses of a single herb are used in an attempt to achieve a
      maximum degree of antioxidant activity.

PMID- 15154289
TI  - Inhibition of tyrosinase by protocatechuic aldehyde.
AB  - The purpose of this study was to determine the inhibitory action of
      protocatechuic aldehyde (PCA) on tyrosinase activity. PCA is one of the compounds
      found in the root of Salvia miltiorrhiza. Our study documented that PCA has a
      potent inhibitory effect on tyrosinase, which catalyzes the rate-limiting step of
      melanin biosynthesis. Although melanin biosynthesis has an essential function
      normally in human skin for defense against ultraviolet light of the sun, its
      abnormal activity as seen in pigmentation disorder could lead to serious medical
      problems. Our data showed that PCA, with concentrations ranging from 1 x 10(-5) M
      to 8 x 10(-5) M, exhibited dose-dependent inhibition of the enzyme activity with
      50% of inhibition at 19.92 x 10(-6) M. A further kinetic analysis on PCA
      inactivation of tyrosinase activity revealed a competitive inhibition of the
      enzyme at the L-tyrosine binding site. The findings of our present study merit
      further research on the applicability of PCA as a potential agent for treatment
      of pigmentation disorder.

PMID- 15154290
TI  - The effect of acupuncture on allergic rhinitis: a randomized controlled clinical
      trial.
AB  - Allergic rhinitis is a common health problem usually treated with drug therapy.
      Some patients experience side effects of drug therapy while others fear the use
      of drugs. Acupuncture is an interesting alternative to traditional treatment. The
      few studies evaluating acupuncture indicate a possible clinical effect on
      allergic rhinitis. This study compared active versus sham acupuncture in 40
      consecutive patients with a history of allergic rhinitis and a positive skin
      test. Patients were randomized and assessed prior to treatment and then
      reassessed after 12 months. Improvements in symptoms using visual analogue
      scales, reduction in skin test reactions and levels of specific immunoglobin E
      (IgE) were used to compare the effect of treatment. For one allergen, mugwort, a
      greater reduction in levels of specific IgE (p = 0.019, 0.039) and skin test
      reaction (p = 0.004) was seen in the group receiving active acupuncture compared
      to the group receiving sham acupuncture. However, this finding might be an
      artifact. No differences in clinical symptoms were seen between active versus
      sham acupuncture, thus the conclusion being that the effect of acupuncture on
      allergic rhinitis should be further evaluated in larger randomized studies.

PMID- 15154291
TI  - The soreness and numbness effect of acupuncture on skin blood flow.
AB  - The purpose of this study was to investigate the effect of the De-Qi sensations
      of acupuncture (sourness-distension and distension-numbness) stimulation. Fifty
      two healthy medical student volunteers were given acupuncture at the Hoku (LI-4)
      acupoint as they were resting. During a test that lasted 30 minutes, their skin
      blood flow was measured at the Quchi (LI-11) acupoint and their palm temperature
      was measured. Our results indicated that acupuncture increased blood flow when
      the De-Qi sensation occurred. If the needle was twirled a few minutes thereafter
      and the De-Qi feeling again occurred, the same blood flow increase was seen
      again. If the needle was not twirled, but the test person felt soreness, numbness
      and heat sensation within a few minutes after needle insertion, the same blood
      flow increase was also seen. After acupuncture, Quchi did not show continuous
      increase of blood flow as did Hoku. Hoku acupuncture also increased palm
      temperature suggesting that the blood flow increased from cutaneous vessel
      vasodilation. In conclusion, when the test person felt the sore and numb De-Qi
      sensation, there was an increase of blood flow at the acupuncture points. Thus,
      our results suggest that increased flow may be one of the mechanisms accounting
      for meridian system responses during acupuncture.

PMID- 15154292
TI  - Electroacupuncture analgesia for surgery in cattle.
AB  - To establish the proper analgesic method by electroacupuncture (EA) for bovine
      surgery, the analgesic effect of dorsal and lumbar acupoints, in addition to the
      combination with dorsal and lumbar acupoints, were investigated in the present
      study. Four Korean native cattle (two males and two females) and 24 Holstein
      Friesian cattle (all females) were used. The experimental animals were divided
      into four groups according to used acupoints: dorsal acupoint group (Tian Ping
      [GV-20] and Bai Hui [GV-5]: 7 heads), lumbar acupoint group (Yap Pang 1 [BL-21],
      Yao Pang 2 [BL-23], Yao Pang 3 [BL-24] and Yao Pang 4 [BL-25]; 5 heads), dorsal
      lumbar acupoint group (Yao Pang 1 [BL-21], Yao Pang 2 [BL-23], Yao Pang 3 [BL-24]
      and Bai Hui [GV-5]; 8 heads) and control group (non-acupoints, the last
      intercostals space and the femoral area; 3 heads). The acupoints were stimulated
      with currents of 2-6 V (30 Hz) in dorsal acupoint group, 0.5-2.0 V (30 Hz) in
      lumbar acupoint group and 0.3-2.5 V (30 Hz) in dorsal-lumbar acupoint group.
      Recumbency time was 10 seconds to 1 minute (except one case) and induction time
      of analgesia was approximately 1 to 6 minutes in dorsal acupoint group. Analgesic
      effect was systemic, including the extremities in dorsal acupoint group. During
      the EA, the consciousness was evident and blepharo-reaction was still present
      under EA in dorsal acupoint group. During the surgery, grades of analgesic effect
      were 6 excellent (6/7, 87.5%) and 1 good (1/7, 14.3%). In addition, induction
      time for analgesia was about 10 minutes in both lumbar and dorsal-lumbar acupoint
      groups. Analgesic areas were found in abdominal areas from the last intercostal
      spaces to the femoral areas, except lower abdomen in lumbar and lumbar-dorsal
      acupoint groups. The consciousness was evident and standing position was
      maintained during EA stimulation in contrast to that of dorsal excellent (1/5,
      20.0%), 3 good (3/5, 60.0%) and 1 poor (1/5, 20.0%) in the lumbar acupoint group.
      Additionally, grades of analgesic effect were 4 excellent (4/8, 50.0%), 3 good
      (3/8, 37.5%) and 1 poor (1/8, 12.5%). On the other hand, pain was present and
      analgesia was not accomplished under EA stimulation in control group. In
      conclusion, analgesia by EA was effective with decreasing order of dorsal
      acupoint > dorsal-lumbar acupoint > lumbar acupoint among groups. It was
      considered that dorsal acupoint group might be useful for operation with
      recumbent position, and lumbar and dorsal-lumbar acupoint groups might be proper
      for operation with standing position.

PMID- 15154293
TI  - The aerobic capacity and ventilatory efficiency during exercise in Qigong and Tai
      Chi Chuan practitioners.
AB  - The objective of this study was to compare cardiorespiratory responses to
      exercise among older Qigong participants, Tai Chi Chuan (TCC) practitioners and
      normal sedentary controls during cycle ergometry. Thirty-six community-dwelling
      men with a mean age of 59.1 +/- 6.6 years participated in this study. Each group
      (Qigong, TCC and control) included 12 subjects with matched age and body size.
      The Qigong group practiced Qigong regularly for 2.3 +/- 1.5 years; the TCC group
      practiced Yang TCC for 4.7 +/- 2.3 years. Heart rate (HR) responses were measured
      during the practice of Qigong and TCC. Additionally, breath-by-breath measurement
      of cardiorespiratory function was performed during the incremental exercise of
      leg cycling. The mean HR during Qigong and TCC practice was 91 +/- 5 bpm and 129
      +/- 7 bpm, respectively. At the peak exercise and the ventilatory threshold
      (VeT), TCC group displayed highest oxygen uptake (VO2), O2 pulse and work rate
      among the three groups. The Qigong group also showed higher oxygen uptake and O2
      pulse than the control group. At the same relative exercise intensity, the Qigong
      group had the highest tidal volume among the three groups. In conclusion, Qigong
      and TCC show a beneficial effect to aerobic capacity in older individuals, but
      TCC displays a better training effect than Qigong due to its higher exercise
      intensity. However, Qigong can enhance breathing efficiency during exercise due
      to the training effect of diaphragmatic breathing.

PMID- 15154294
TI  - Relative exercise intensity of Tai Chi Chuan is similar in different ages and
      gender.
AB  - This study aims to determine the relative exercise intensity of classical Yang
      Tai Chi Chuan (TCC) in different ages and gender. One hundred TCC practitioners
      (54 men and 46 women) aged 25 to 80 years participated in this investigation. Men
      and women were separated into three groups: young (25-44 y/o), middle-aged (45-64
      y/o) and elderly (65-80 y/o). Heart rate (HR) responses during TCC practice were
      measured by using electrocardiographic telemetry. An exercise test with breath-by
      breath measurements of cardiorespiratory function was also performed for each
      subject during the incremental exercise of leg cycling. Measurements obtained
      during the TCC practice and exercise testing were compared to determine the
      exercise intensity of TCC. While performing TCC, the mean HR of men was 141 +/-
      12 bpm, 132 +/- 9 bpm and 120 +/- 10 bpm in the young, middle-aged and elderly
      groups, respectively. Men practiced TCC with mean HR corresponding to 57.8 +/-
      3.7%, 56.6 +/- 3.4% and 55.1 +/- 3.1% of heart rate reserve (HRR) in the three
      groups. Meanwhile, the mean HR of women was 136 +/- 10 bpm, 126 +/- 11 bpm and
      115 +/- 12 bpm in the young, middle-aged and elderly groups, respectively. Women
      practiced TCC with mean HR corresponding to 52.7 +/- 2.8%, 51.5 +/- 2.6% and 50.3
      +/- 2.9% of HRR in the three age groups. The results demonstrate that classical
      Yang TCC is an exercise with moderate intensity, and its exercise intensity is
      similar across different ages in each gender. In conclusion, TCC is an aerobic
      exercise and suitable for participants of different ages and gender to improve
      their functional capacity.

PMID- 15154295
TI  - [Coronary artery bypass grafting. Does the decreasing number of surgeries lead to
      the need for centralizing operations?].

PMID- 15154296
TI  - [Is the price right for the hearing aids in Finland: need more money or
      efficiency?].

PMID- 15154297
TI  - [Articles written by Matti Ayrapaa and Reijo Waara, published in Duodecim 1885
      1899, now available on the World Wide Web].

PMID- 15154298
TI  - [The treatment of Parkinson's disease with electric stimulation].

PMID- 15154299
TI  - [Nuclear lamins and their diseases].

PMID- 15154300
TI  - [The occurrence of hearing defects among adults, rehabilitation with hearing aid
      and the costs].

PMID- 15154301
TI  - [Differential diagnosis of sporadic and variant form of Creutzfeldt-Jacob disease
      ].

PMID- 15154303
TI  - [Diagnosis and treatment of synovial arthritis].

PMID- 15154302
TI  - [Future directions for drug treatment of drug-resistant depression].

PMID- 15154304
TI  - [Health problems of young women].

PMID- 15154305
TI  - [Painting by Juho Rissanen].

PMID- 15154306
TI  - [Developments in blood transfusion].

PMID- 15154307
TI  - [Special features of blood transfusion to children].

PMID- 15154308
TI  - [Immunological aspects of blood transfusion preparations].

PMID- 15154309
TI  - [Prophylactic platelet transfusion in patients with hematologic diseases].

PMID- 15154310
TI  - [The microbial safety of transfusion products].

PMID- 15154311
TI  - [Blood and plasma transfusion in the treatment of acute blood loss].

PMID- 15154312
TI  - [Blood transfusion safety].

PMID- 15154313
TI  - Illinois court upholds imposition of summary suspension of physician's open-heart
      surgical privileges. Lo v. Provena Covenant Medical Center.

PMID- 15154314
TI  - Distinguishing warrants from subpoenas.

PMID- 15154316
TI  - Hospitalwide quality improvement in Thailand.
AB  - BACKGROUND: In 1999 King Chulalongkorn Memorial Hospital, a 1,500-bed teaching
      hospital in Thailand, started planning and implementing a hospitalwide quality
      improvement program, as required for accreditation. DEPLOYING THE NINE-STEP
      LADDER STRATEGY: The steps in the strategy were as follows: (1) ensure commitment
      and formulate mutual strategies; (2) develop teams, technical staff, and support;
      (3) pilot new improvement activities and expand existing quality programs; (4)
      improve core systems and functions; (5) expand to the whole organization; (6)
      perform self-assessment and internal survey, (7) complete the incomplete; (8)
      submit the request for accreditation; and (9) improve continuously for
      excellence. For example, for step 3, the hospital set up five pilot cross
      functional quality lead teams: the infection control committee, emergency-care
      patient care team, medication system team, laboratory and x-ray services team,
      and operating room team. RESULTS: The hospital was accredited by the Institute of
      Hospital Quality Improvement and Accreditation, Thailand. Improvements were shown
      in inpatient mortality, patient satisfaction, and reporting of patient risk
      incidents and the number of serious incidents. LESSONS LEARNED: Critical success
      factors in implementing a hospitalwide QI program were as follows: (1) role of
      leadership, (2) need for "quality strategists," (3) physician involvement and
      participation in QI teams, (4) vertical and horizontal communication, (5)
      performance drivers, (6) simplicity in continuous quality improvement, and (7)
      the value of a learning culture.

PMID- 15154315
TI  - From research to daily clinical practice: what are the challenges in
      "translation"?
AB  - BACKGROUND: Translating research findings into sustainable improvements in
      clinical and patient outcomes remains a substantial obstacle to improving the
      quality and safety of care. The Agency for Healthcare Research and Quality funded
      two initiatives to assess strategies for improvements--Translating Research into
      Practice (TRIP). The TRIP II initiative supported 13 quality improvement
      projects. SURVEYING THE TRIP II STUDIES: The principal investigators (PIs) of the
      13 projects were surveyed regarding encountered barriers to implementation at 6
      months and 18 months (when they were also asked about solutions). RESULTS: Seven
      of the 13 PIs responded to the survey at both times--6 and 18 months. For each
      project stage--Select a TRIP focus and develop intervention strategies (Stage 1),
      Conduct the intervention (Stage 2), and Measure the Impact (Stage 3)--barriers
      were described, and field-tested solutions were provided. For example, for Stage
      2, if the target audience lacked buy-in and would not participate, solutions
      would be to get up-front buy-in from all staff, not just leaders; address root
      causes of problems; use opinion leaders and incentives; plan interventions ahead
      and provide make-up videos; and accept that targets vary in their readiness to
      change. DISCUSSION: The framework and examples provided should help overcome
      challenges in any work in which research findings are applied to clinical
      practice.

PMID- 15154317
TI  - Shifting care of chronic ventilator-dependent patients from the intensive care
      unit to the nursing home.
AB  - BACKGROUND: Among the most resource intensive and challenging of medical needs is
      the treatment of patients requiring long-term or chronic mechanical ventilation.
      Expenditures are significant, and definitions of "successful weaning," are often
      inconsistent. A weaning program was initiated for patients referred to a stand
      alone nursing home ventilator unit. METHODS: Weaning entailed standardized
      weaning protocols, enhanced socialization, a multidisciplinary approach to care,
      empowerment of staff to initiate weaning, and aggressive utilization of
      noninvasive positive pressure ventilation (NPPV) in selected patients. RESULTS:
      Sixty-eight (67%) of 102 patients were successfully weaned during a six-year
      period. NPPV facilitated successful weaning in 27 (26%) of 102 patients. Of the
      28 chronic ventilator-dependent patients admitted with a neuromuscular etiology
      for respiratory failure, NPPV was utilized in 73% (8/11) of the successfully
      weaned patients. Total variable costs per ventilator per patient per day for the
      years 1998-2000 were $319.79, $302.75, and $297.59. Six-year cost savings for
      referring hospitals were estimated at $18.5 million. DISCUSSION: Incentives were
      aligned between the hospital, nursing home, and physicians to develop a
      financially stable model. Developing an off-site nursing home ventilator unit
      resulted in significant cost savings to the referring hospitals and positively
      affected patient flow.

PMID- 15154318
TI  - A physician house call program for the homebound.
AB  - BACKGROUND: A growing number of homebound frail older adults have multiple
      chronic diseases with frequent flare ups of acute episodes. A physician house
      call program affiliated with a nonprofit community health system was deployed as
      a strategy to improve quality of care for homebound patients. PROGRAM
      DESCRIPTION: A medical team (either a physician and a medical assistant or a
      nurse practitioner), with a vehicle filled with portable medical equipment and
      supplies, fulfills the house call and primary care physician functions,
      establishes diagnoses, designs a treatment plan, arranges for any other needed
      services, and fosters continuity of medical care. EVALUATION: Interviews and
      focus groups with selected patients, family caregivers, program staff, and other
      service providers indicated that the program operated consistently with its
      intent. For example, the patient and caregiver interviews converged on four major
      themes: (1) the program improves patients' medication and health management and
      optimizes health, (2) caregivers felt more informed about the patients' medical
      conditions and medications and relieved of the burden of transporting patients to
      physicians, (3) the program reduces use of hospital and emergency services, and
      (4) the programs enables patients to die at home. DISCUSSION: The success of any
      future programs and further replications will depend on creating trusting
      relationships with local service providers and getting decision makers of
      affiliated community health systems or hospitals to embrace the necessary vision.

PMID- 15154319
TI  - Altering meperidine prescribing patterns in a university teaching hospital.
AB  - Education and operational changes and restrictions led to a sustained reduction
      in meperidine use.

PMID- 15154320
TI  - Who left the defibrillator on?
AB  - BACKGROUND: Two related scenarios involving defibrillator devices reveal how
      inadvertent hazardous design can go unnoticed until engineers or patient safety
      personnel use human factors engineering (HFE) analysis. The first adverse event,
      in which the device was inadvertently turned off while being used to externally
      pace the patient's heart, resulted in an increased length of stay. The second
      scenario describes a similar close call and the useless acts of sanctioning the
      nurse and firing the engineer technician. COMMENTS AND RECOMMENDATIONS: Feedback
      to the end user about a device's status is an important design issue. It does not
      take much expertise to detect when there are problems with "dialogue" from the
      device to the person (that is, feedback). Many HFE issues have been cited in
      emergency care areas, and many medical devices--not just defibrillators--do not
      have readable and understandable feedback to the end user or the kind of
      automation that would make the wrong action harder to accomplish. All the
      interactions of multifunction devices with end users in a hectic, noisy, and
      dynamic environment need to be usability tested and validated. Nurses and
      engineering personnel can be trained to more easily see HFE design issues--and
      not dismiss them as individual failings or "someone else's job." Medical device
      companies are starting to follow the guidelines and regulations that should help
      prevent adverse events. CONCLUSION: The defibrillator's design problems had
      successfully masqueraded as "expected" glitches with hospital electrical
      utilities, personnel shortcomings, and personality problems. Adverse events
      related to seemingly simple devices can be prevented with HFE analysis.

PMID- 15154321
TI  - Information-to-go: publishing organization-specific information for personal
      digital assistants.
AB  - A Web-based resource enables staff to access to patient management information.

PMID- 15154322
TI  - [The role of leukocytes in microcirculation dynamics in the norm and pathology].
AB  - The physiological functions grow to be more perfect and complicated in the
      process of evolution. However, a developing function could display some evidence
      of regress and, in certain cases, it can trigger serious diseases including
      autoimmune ones. Conventionally, we refer to the above cases as to "errors" of
      evolution. The present case study deals with a negative factor of leukocytes in
      the cerebral microcirculation. Leukocytes were shown, experimentally, to inhibit
      the capillary blood flow owing to their big volume (2-2.5-fold more versus that
      of erythrocytes). An increasing trend to adhesion due to hypoxia is responsible
      for shaping of leukocytes' conglomerates, which cause the occlusion of venules
      and of the smallest cerebral veins. It entails the effect known as "no re-flow"
      resulting in death.

PMID- 15154323
TI  - [Integral evaluation of autonomic nervous system function].

PMID- 15154324
TI  - [The role of cytokines and interferon-alpha in the pathogenesis of chronic
      diffuse diseases of the liver].
AB  - The cytokine profiles were investigated in 171 patients with chronic hepatitis
      (CH) and in 173 patients with liver cirrhosis (LC). Increasing mean
      concentrations of IFN-alpha, TNF-alpha, IL-4 and IL-6 in blood serum as well as
      of the functional (antiviral and cytolytic) activity of IFN-alpha and TNF-alpha
      were found to be typical of a majority of CH and LC patients. Higher
      concentrations of IFN-alpha, IL-1, TNF-alpha and IL-6 in blood serum of CH
      patients are more typical of viral hepatitis versus alcoholic one. The
      replicative activity of hepatotropic viruses induces a powerful cytokine
      response. The LC etiology did not have any essential impact, in a majority of
      cases, on the blood-serum cytokine profile. A low function activity of TNF-alpha
      in blood serum signifies that the biological effects of the above cytokine are
      blocked. Finally, such analysis of the parameters of concentrations and
      functional activity of serum cytokines ensures a more objective evaluation of the
      pathogenetic disease mechanism and provides for prognosticating its outcome.

PMID- 15154325
TI  - [The parietal mucin microbial population in different sections of the human
      gastrointestinal tract].
AB  - Microbiological examinations of the human-colon parietal mucin were made in
      different sections of the human gastrointestinal tract (GIT). Biopsy samples of
      the human colon mucus tunic were used as the research material. Convincing data
      were found by research on the importance of the anatomic-and-morphological factor
      in shaping-up of microbiocenosis of the colon-wall parietal mucin. It was
      established that, depending on a GIT section, not only the quantitative and
      qualitative composition of normal microflora but also the nature of inter-microbe
      interactions are subject to changes. In particular, biopsy materials of the small
      intestine parietal mucin are much different from that of the colon. The colon
      section from the ascending colon to the sigmoid colon has, with some exceptions,
      an identical microbial composition. At the same time, the rectum is significantly
      different from other colon sections. The results are suggestive of the below
      cluster-type pattern of parietal biological material: microorganisms are
      clustered as small domains with certain specific and quantitative compositions.
      It was established that, although feces and parietal mucin have a similar species
      composition of microorganisms, still, there is a number of essential differences
      between them in as far as the frequency ratio and the microorganism concentration
      are concerned, which signifies a certain degree of isolation of the above biopsy
      materials. Finally, a certain isolation degree of the feces biopsy materials and
      of the parietal ones was established.

PMID- 15154326
TI  - [Antigen properties of oral intake whole-culture preparations from Neisseria
      meningitides of serogroups A, B and C].
AB  - A new technology of deriving the whole-culture peroral meningococcal mono
      vaccines of serogroups A, B and C from the acetone-inactivated cultures was
      experimentally substantiated. The latter cultures were obtained through computer
      aided continuous-flow cultivation of Neisseria meningitides of the above
      serogroups in the bioreactor with a synthetic nutrient medium. The whole-culture
      meningococcal mono-preparation of 3 serogroups comprised a complete set of
      antibodies, i.e. polysaccharides (PS), external membrane proteins (EMP) and
      lipopolysaccharides (LPP), in their native condition. High levels of IgG to PS,
      EMP and LPP were detected in blood sera of rabbits, which had been perorally
      immunized by the above preparations; such high levels persisted for a long time
      (303 days--observation period). It is noteworthy, that in accumulating of IgG to
      all investigated antigens of meningococcus of serogroups A and C, the optimal
      doses of whole-culture peroral monovaccines did not exceed the culture doses used
      to derive the hyper-immune sera at intravenous immunization.

PMID- 15154327
TI  - [Experimental study of antioxidant properties of a new dry extract (Nephrophyt)
      obtained on the basis of therapeutic vegetable raw material].
AB  - The antioxidant properties of a new Russian vegetable preparation (Nephrophyt),
      known for its nephroprotective effect, were investigated experimentally in vivo
      and in vitro in modeled systems applicable to evaluating the capture of super
      radicals on the basis of nitro-blue tetrazole (NBT). The preparation was
      demonstrated to oppress effectively the formation of the primary peroxidation
      products, i.e. diene conjugates, in rats in no way affected the synthesis of the
      peroxidation secondary products, i.e. malonic dialdehyde. The found effect
      correlates with a pronounced ability of the preparation to act as a "capturer" of
      02-radical in vitro. Besides, the outlooks for using Nephrophyt as an antioxidant
      and as a tool for investigating the peroxidation reactions are under
      consideration.

PMID- 15154328
TI  - [A comparative description of amyloidosis in monkeys].
AB  - The paper contains the results of a postmortem study of 461 cases of amyloidosis
      in monkeys of 4 species (Papio hamadryas, Macaca mulatto, Macaca fascicularis and
      Macaca nemestrina) from the Sukhumi and Adler primatological facilities.
      Emergence of amyloidosis was found to be dependent on age; the frequency ratio at
      which separate organs are affected is presented; the specific disease signs are
      described for different monkey species. Generalized and isolated cases of
      amyloidosis are elucidated with the liver being the most vulnerable organ in
      macaques (64%) and the kidneys--in baboons (94%). A comparative description of
      different forms of amyloidosis in monkey and man was made use of to suggest using
      the amyloidosis in monkeys as a model process for studying the pathology in man.

PMID- 15154329
TI  - [Methodology and research of public health].
AB  - The statistical sources now available within Russia's healthcare systems as well
      as their potentialities in respect to evaluating the public health standards are
      analyzed in the paper both analytically and comparatively. The most informative
      sources are enumerated; additionally to the verified data of the medical-and
      demographic nature, parameters of the integrated health condition, which are
      based on questionnaires, self-assessment and medical documentation known to
      respondents, are suggested. The above methods and evaluation tools, that are in
      line with the world standards, ensure the compatibility of data and provide for a
      more tense usage of joint healthcare programs.

PMID- 15154330
TI  - [Infectious pathology of monkeys: a brief description, potential experimental
      research, safety for attendants at primate care facilities and laboratories].
AB  - Infectious diseases of monkeys, including the bacterial anthroponosous and
      zoogenous as well as viral infections, are described in the paper. A bulwark of
      research resulted from authors' independent long-term observations of monkey
      pathologies at Sukhumi and Adler primatological facilities. Pathologies are
      elucidated, which are better to be modeled in monkeys; there are also diseases
      that can be studied only in monkeys. Monkey agents were isolated, which are
      dangerous to humans attending the animals at primatological facilities and
      laboratories.

PMID- 15154331
TI  - Taking the nickel out of the medicine.
AB  - Several important alloys used in medical technology contain nickel, an element
      that has significant metallurgical qualities but serious toxicological concerns.
      This article addresses the question of whether it makes sense to try to eliminate
      the nickel from these alloys.

PMID- 15154333
TI  - Electronics will transform drug delivery devices.
AB  - The drug delivery device sector will be transformed by electronically controlled
      alternatives that will maximise user safety and medical effectiveness and open
      the way to the introduction of high-power, next-generation drugs. Current
      business partnerships will need to change to allow this to happen.

PMID- 15154332
TI  - Microfluidics: an opportunity for trend-setting drug delivery.
AB  - The past has demonstrated that when working with microfluidics only the following
      scenario is likely to lead to successful system development: a high level of
      component integration at an early development stage with an application-specific,
      simple (reliable) design, and a high interdisciplinary level of know-how over a
      broad range of technologies, pharmacology and medicine. The mere application of
      existing nonspecifically designed or outsourced microfluidic components is likely
      to fail because the system behaviour in the microworld is far different from that
      in the macroworld.

PMID- 15154334
TI  - Patents versus settling for the soft option.

PMID- 15154335
TI  - How to validate a packaging process.
AB  - Some of the key elements of achieving a validated packaging process are
      described. A peel-pouch sealing machine is used as an example.

PMID- 15154336
TI  - Guidance on submitting quality system information.
AB  - The Food and Drug Administration's final guidance document on the type of quality
      system information that should be submitted in some types of premarket
      submissions was published in February 2003. The final guidance replaces previous
      draft guidance. This article discusses the final guidance document.

PMID- 15154337
TI  - Does standardisation have a role in nanotechnology and medicine?
AB  - A look at what nanotechnology means in the context of medical science and what
      developments are in the pipeline.

PMID- 15154338
TI  - Characterisation of particle deposition and penetration from nasal sprays.

PMID- 15154339
TI  - Switzerland's medical technology potential.
AB  - Favoured for its central European location and sophisticated scientific
      environment, Switzerland's medical device industry is thriving.

PMID- 15154340
TI  - Automating stent crimping.

PMID- 15154341
TI  - [Main directions and perspectives of clinical applications of robot manipulators
      on soft tissues].

PMID- 15154342
TI  - [Effect of reflex-segmental massage on central hemodynamics in healthy people].
AB  - Bioimpedance tetrapolar rheopolygraphy was made in 18-22-year-old athletes in
      lying position and active orthostasis using computer technology Kentavr PRS
      (Microlux). The study group of 40 men received a 10-day course of massage
      including classic massage of the spine and neck, reflex-segmental massage of the
      left scapula, region between the left scapula and the vertebral column, left
      great chest muscle and sites of left attachment of the ribs to the chest. The
      examinations were made before the massage and after it. The results demonstrate
      an optimizing effect of reflex-segmental massage technologies on central
      hemodynamics.

PMID- 15154343
TI  - [Biomechanical and physiological substantiation for application of functional
      muscle electrostimulation in performing rhythmic movements on bicycle ergometer].
AB  - Kinematic and electromyographic parameters in conduction of rhythmic movements on
      the bicycle ergometer were studied in a group of healthy subjects. It is shown
      that these movements are characterized by a stable biomechanical and innervation
      stereotype consisting of two interacting synergies: flexor and extensor. Force
      extensor synergy plays the key role which provides both triggering and
      maintenance of certain rhythm of rotation. Flexor synergy is primarily
      corrective. Basing on the data obtained, stimulated muscles are selected in basic
      phases of the cycle, algorithms of time and amplitude programs of muscle
      electrostimulation in conduction of bicycle ergometry are proposed.

PMID- 15154344
TI  - [Photosensory stimulation in the therapy of patients with neurosis and astheno
      depressive syndrome].

PMID- 15154345
TI  - [Use of cortexin electrophoresis in the prophylaxis of cerebral strokes].
AB  - Cortexin was used in prophylaxis of stroke among patients with cerebrovascular
      diseases. A course of cortexin therapy proved highly effective in the treatment
      of disorders of brain functions.

PMID- 15154346
TI  - [Effect of sanatorium treatment on hormonal disorders in patients with sequelae
      of craniocervical trauma].
AB  - Craniocervical trauma brings about pathology of the central regulatory
      mechanisms, functional insufficiency of which persists for many years and is
      responsible for specific features of traumatic disease of the brain with
      development of the syndrome of posttraumatic regulatory disorders of the nervous
      endocrine-immune system. The authors propose methods of differential therapy of
      posttraumatic hormonal disorders in sanatorium.

PMID- 15154347
TI  - [Diurnal arterial blood pressure monitoring in hypertensive patients treated with
      pulse low-frequency alternating electric field].
AB  - The effect of pulse low-frequency alternating electric field (HI-VAMAT-200 unit)
      on 24-h profile of arterial pressure was studied in 30 hypertensive patients. The
      evidence obtained at 24-h blood pressure monitoring showed that the above
      physiotherapy increased a nocturnal surge of arterial pressure and normalized its
      24-h profile more effectively than conventional pharmacotherapy.

PMID- 15154348
TI  - [Pro- and antioxidant effect of electromagnetic fields of extremely high
      frequency (460 MHz) on brain tissues in experiment].
AB  - The article concerns biological effects of non-ionized electromagnetic
      irradiation which is considered in modern world as a serious ecological factor.
      Influence of decimetric microwave irradiation (460 MHz) on free radical processes
      in the rat brain tissues--visual cortex and hypothalamus--were investigated.
      Oxidative effects of both lipid peroxidation and specific activity of glutathione
      reductase were determined. It is shown that whole body irradiation for up to 4
      weeks results in considerable changes of the above indices dependent on the
      irradiation intensity and age of the animals. Decimetric microwaves have oxidant
      effects at high intensity irradiation (SAR--15 mW/kg), while these effects are
      antioxidant at low intensity (SAR--5 mW/kg). Physiological implications of
      different oxidative metabolic responses of the hypothalamus and the cortex to
      microwaves irradiation are discussed.

PMID- 15154349
TI  - [Indices of endogenic intoxication and protein metabolism in early therapy with
      ultrasonic frequency currents after urgent gynecological operations in children].
AB  - The examination covered 61 girls (mean age 12.1 +/- 0.5 years) operated urgently
      by a laparotomy approach for benign tumors and tumor-like lesions of the ovaries
      with following treatment started 36 hours after surgery. 30 girls were exposed to
      suprasonic frequency currents (SFC), 11 girls received sham procedures and 20
      girls were not exposed to SFC-therapy. SFC-therapy was effective. Serum tests for
      total proteins, globulins, urea, creatinine, aspartate aminotransferase, medium
      size molecules, acid-soluble fraction of nucleic acids have shown that
      postoperative SFC-therapy promoted lowering of endogenic intoxication and
      improvement of protein metabolism.

PMID- 15154350
TI  - [Role of heat and chemical factors of sulphide mud in its antioxidant action in
      experiment].

PMID- 15154351
TI  - [New principles in the assessment of body functional status during sanatorium
      treatment].
AB  - 151 children aged 6-14 years received sanatorium treatment in Gelenzhik. The
      children were examined clinically before and after the treatment with estimation
      of nonspecific adaptation of the organism (NSAO) by L. Kh. Garkavi et al (1990)
      and adrenoreactivity by beta-adrenoreception of erythrocytes (b-ARE) using ARM
      AGAT kits (Agat-Med., Moscow). The highest percent of favourable NSAO was seen in
      children with initially high adrenoreactivity. In children with subnormal
      adrenoreactivity it was 3-7 times less. Sanatorium treatment reduced b-ARE and
      improved NSAO in most of the children. In children with initially high
      adrenoreactivity (b-ARE 4-12 r.u.) who had had acute respiratory viral infection
      or tonsillitis, unfavourable NSAO number was higher. The trends in b-ARE and NSAO
      suggest the necessity of these indices evaluation for individual choice of
      sanatorium treatment and monitoring of its efficiency.

PMID- 15154352
TI  - [Energetic aspects of adaptation processes and rehabilitation].
AB  - The study of energy metabolism and phenotypical adaptation in patients with ulcer
      disease has revealed deficiency of energy metabolism and defective phenotypical
      adaptation in the form of its tension or failure of adaptive processes.
      Sanatorium treatment with oral intake of mineral water, mineral baths,
      fangotherapy, limontar-electrophoresis and millimetric waves promoted
      normalization of energy metabolism and adaptive processes. Impact of different
      physiotherapeutic factors on energy metabolism and adaptation of the organism is
      described.

PMID- 15154353
TI  - [Local and systemic hemodynamic reactions as components of action of local
      lowered pressure].
AB  - It is shown that low atmospheric pressure produces a positive effect on systemic
      and regional hemodynamics in patients with diseases of the small pelvis and lower
      limbs manifesting by increased speed of regional blood flow due to lowering of
      peripheral resistance in small caliber arteries and arterioles, reduction of
      venous congestion and improvement of microcirculation. This makes hypobarotherapy
      perspective in treating diseases running with arterial ischemia and venous
      congestion.

PMID- 15154354
TI  - [Effect of alternating low-frequency magnetic field on central hemodynamics in
      patients with hypertension].

PMID- 15154355
TI  - [Physical rehabilitation of elderly patients with chronic cardiac failure].

PMID- 15154356
TI  - [Efficacy of nonpharmacological treatment of neurocirculatory asthenia of cardial
      type].

PMID- 15154357
TI  - [Study of microcirculation with laser Doppler flowmetry in patients with facial
      nerve neuritis under the influence of physiotherapy].

PMID- 15154358
TI  - [Comparative efficacy of anemia treatment in mountain health resort and using
      normobaric intermittent hypoxic training].

PMID- 15154359
TI  - [Exercise therapy and massage in the treatment of piriformis muscle syndrome in
      pregnant women].

PMID- 15154360
TI  - [Rehabilitation of patients with occupational pathology at Siberian health
      resorts].

PMID- 15154361
TI  - [Principles of evidence-based medicine in physiotherapy].

PMID- 15154362
TI  - [Experimental-clinical substantiation of the diet therapy with zosterin in kidney
      diseases].
AB  - The results of enterosorbent of marine origin zoosterol application under
      nephropathy are cited. Detoxicational, lipid corregated action of zoosterol was
      revealed as a result of experimental researches on nephrocalcinosis model, but
      calcium accumulation was observed in animals' kidney tissue. Clinical
      examinations including zoosterol application and dietotheraphy showed the
      decreasing of heightened calcium level in serum and urine, cholesterol and
      triglycerides, stabilization of membranodestructive processes in urinary
      excretive system for patients with chronic pyelonephritic.

PMID- 15154363
TI  - [Immune correction in the therapy of patients with prevalent psoriasis with the
      help of amino acid complex].
AB  - In patients with prevalent psoriasis a positive influence amino acid addition
      (with the standart therapy) on the clinical status of patients and their immune
      status induces. As a result of this addition use the lesion area diminished,
      prolongation of remission periods, reduction of the time spent in hospital.

PMID- 15154365
TI  - [The use of food supplements - beverages and concentrated food products in
      tablets made from plants in sanatory and health resort rehabilitation of patients
      with chronic pathology].
AB  - The effectiveness of a recovery complex optimization in conditions of the
      sanatorium-resort rehabilitation of patients with chronic pathology by provision
      of the dietotherapy ration balance on nutrients, the use of natural (of the plant
      raw material cryopowders in the form of teas and tableted forms) and the
      "Centrum" synthetic vitamin-mineral complexes, probiotics was substantiated and
      demonstrated.

PMID- 15154364
TI  - [The experience of using selenium-containing biologically active food supplements
      by patients during rehabilitation period after myocardial infarction].
AB  - Usage of rehabilitation complex with "Selenes-korona" for patient with myocardial
      infarct resulted in positive dynamic of blood lipids and albumins. The decrease
      of intensity of lipid peroxidation and increase SOD activity was also revealed.
      The results shoved that antioxidant complexes may be recommended for
      rehabilitation complex for patient with myocardial infarct.

PMID- 15154366
TI  - [Biologically active food additives for correction of the chronic fatigue
      syndrome].
AB  - The syndrome of chronic fatigue is a rather new pathology, included in ADS 10.
      There is no specific treatment. Vitamins and microelements are very important for
      the prevention and treatment of CFS. Of special significance are BAA on the basis
      of yarsts, which are universal in their biological chemical composition and
      contain high amounts of vitamins B, K and essential aminoacids. The aim this work
      is clinical diagnostic of "Nagipol" use, made on the basis of beer yeasts, for
      the prevention and treatment of CFS. Clinical-dietologic study showed that
      "Nagipol" biologically active additive, useful in CFS, prodvecins clinical status
      improvement in CFS, positively influencing cognitive CNS functions, symptoms of
      psychoemtional instability, normalizing blood biochemical parameters, can be
      recommended as one of the addition element in diet-therapy of patients with
      excessive body mass and otesitg with the associated CFS. Recommended "Nagipol" as
      preventive-medical dietetic means for this pathology.

PMID- 15154367
TI  - [Vitamin sufficiency of young basketball players].
AB  - The investigation of vitamin sufficiency of young basket-ball players 14-16 years
      old (17 girls and 14 boys) has been carried out 59-77 per cent of the children
      had the deficiency of B group vitamins, 24-54 per cent--vitamin E insufficiency,
      most of them (82-100 per cent)--deficit of carotenoids while they were
      sufficiently vitamins C and A supplied. The girls were supplied with vitamins
      better than boys. There was no one adequately supplied with all vitamins among
      boys while 12 per cent of girls had adequately sufficiency. The girls had deficit
      of 1-2 vitamins more often whereas the combined insufficiency of 3-4 vitamins
      took place in 1.8-2.3 fold more frequently among boys. Daily intake of
      multivitamin containing 10 vitamins in daily recommended doses, lipoic acid,
      methionin and 9 minerals by boys lead to their blood plasma vitamin C, E, B-2 and
      beta-carotene level increase. Vitamin C insufficiency disappeared. Deficit of
      beta-carotene and vitamin B-6 became 1.5 fold rarely, vitamin B-2--2 fold,
      vitamin E--6 fold. Thus daily intake of recommended doses of vitamins eliminates
      biochemical signs of vitamin deficiency.

PMID- 15154368
TI  - [The medical-biological evaluation of the bread made of bioactivated wheat
      grain].
AB  - The brief description of a new kind of bread made of bioactivated wheat grain and
      obtained by the authors is given. The main stages of carrying out the medical
      biological evaluation test of the product on white rats and its results are
      described. The data of the clinical tests on the new bread application by 45
      patients with different somatic pathologies are given. They acknowledge its good
      digestion and high clinical efficiency.

PMID- 15154369
TI  - [Essential trace elements distribution in food micro algae Spirulina platensis
      biomass fractions].
AB  - Distribution of some trace elements elements (zinc, selenium, iron, manganese,
      chromium) was characterized in enriched biomass of food micro algae Spirulina
      platensis by means of water-methanol fractionation. The majority of said trace
      elements was shown to be incorporated in intercellular hydrophylic fraction, e.g.
      could be connected to cellular proteins. This result enable the conclusion, that
      Spirulina is a suitable matrix for biotechnological incorporation of new food
      trace elements preparations.

PMID- 15154370
TI  - [The search of antioxidants in plant root's extracts of the carline thistle].
AB  - The carrying out tests of water-extracts of carline thistle (plant pink,
      Caryophyllaceae) in Kazakhstan (extract 1) and gathered in the Primorye region
      (extract 2). The method of spectral and thin layer chromatography silicagel
      plates contain phenolys components. It is found out that both extracts contain
      the same bonds with the max, uptake of long waves lambda = 282 hm and lambda =
      260 hm. Besides, extract 2 has significant quantity of substances with the max,
      uptake lambda = 272 hm and substance with the max, uptake lambda = 330 hm. When
      determining with the help of standard tap the chemical nature of the substances,
      which have antioxidant characteristics, we settled out that antioxidant of
      soapwort possibly can be coffee acid and nonpolar flavonoid of unstated nature.

PMID- 15154371
TI  - [Bioelectrical impedance analysis: opportunities and prospects of using this
      method in practical dietology].
AB  - In clinical practice spectral bioelectrical impedance analysis is a sensitive
      enough method in an estimation of changes of structure of a body composition and
      distribution of a liquid on sectors at various modes of a feed in norm and
      pathology. The analysis of parameters allows to direct the expert on creation of
      the individual circuits of a feed, is especial at the patients who are taking
      place on long treatment.

PMID- 15154372
TI  - [The influence of low intensive chemical loads on homeostasis and the problems of
      prophylaxis].
AB  - The systematic influence of chemical on the main components of homeostasis is
      described and the possibility of prophylactic measures on this level to avoid the
      modifying effect of low level chemical factors is discussed.

PMID- 15154373
TI  - [Immunohistochemical study of the prostate-specific antigen in prostatic cancer].
AB  - Prostate-specific antigen (PSA) is secreted both by normal epithelial prostatic
      cells and cell of prostatic carcinoma (PC). No parallelism exists between the
      degree of PC differentiation and the type of PSA secretion. PSA concentration in
      the peripheral blood not always corresponds to the intensity of its
      immunoreactivity on the tissue level. Amount of PSA in the blood depends on the
      stroma vascularisation and number of cells contacting with the organ stroma. A
      decrease of PSA in the peripheral blood due to therapy may be combined with high
      intensity of its synthesis in tumor cells. PSA immunohistochemistry may be
      recommended as a method of PC clinical course monitoring and dynamics of its
      changes in the course of carcinoma therapy.

PMID- 15154374
TI  - [Immunohistochemical study of the expression of receptors to steroid hormones in
      endometrial hyperplastic processes].
AB  - We examined 39 women with normal endometrium and 139 women with glandular-cystic
      hyperplasia of the endometrium (without atypia). According to clinical
      manifestations of hyperplasia, the patients were divided into 3 groups: 74 (53%)
      had reestablishing menstrual function after total curettage (group 1); 42
      patients (30%) with glandular-cystic hyperplasia after curettage and hormonal
      therapy with progesterone and synthetic progestins (duration 3 to 6 months) had
      no repeated pathology of the endometrium (group 2); endometrial hyperplasia
      recurred 2 and 3 times as showed biopsies during 2-5 years of observation in 23
      (17%) women (group 3). Immunohistochemical tests of normal endometrium revealed
      correlations between stages of menstrual cycle and steroid hormone receptors in
      nuclei of glandular epithelium and stromal cells. Maximum sensitivity of
      glandular epithelium to estrogen and pronounced expression of estrogenic
      receptors were observed at middle and late stages of proliferation. High
      sensitivity of glandular epithelium to progesterone was registered at middle and
      late stages of proliferation and early stage of secretion. Two types of hormone
      receptor expression were observed. Type 1 typical for the endometrium of middle
      and late stage of proliferation was characterised by a high content of receptors
      to E2 and P in glandular epithelium and stromal cells. Type 2 was observed in
      patients with recurring glandular hyperplasia and was characterised by a mosaic
      picture up to complete absence of receptor expression in nuclei of some glands
      and stromal cells. The detected zones free of receptors to estrogens and
      progesterone evidence for local disturbance of a regulating role of signal
      pathways of sexual steroids and can serve a substrate for formation of tissue
      autonomy.

PMID- 15154375
TI  - [Assessment of the significance of histological, immunohistochemical and clinical
      data in the diagnosis of lymphoproliferative skin diseases in conformance with a
      consensus by international experts].
AB  - The diagnosis of lymphoproliferative diseases of the skin remains a challenging
      problem in dermatology and requires a multidisciplinary approach. In our
      retrospective study two dermatopathologists independently reviewed 49 cases of
      skin lymphomas to determine the impact of diagnostic methods such as clinical
      examination, histological evaluation, and immunohistochemistry. The study was
      carried out in four independent review sessions consisting of (1) a review of
      histological sections only, (2) a review of immunohistochemical sections, (3) an
      introduction of the detailed clinical data, history, and staging information, and
      (4) and introduction of the follow-up. The agreement with the consensus was
      analyzed for every session, and statistics were calculated to evaluate the
      interobserver reliability. The agreement level with the consensus diagnosis was
      18.8% for B-cell lymphomas and 12.5% for T-cell lymphomas after the first
      session, respectively, improved to 56.3% and 43.8% after the second session; to
      100% and 79.7% after the third session, and to 100% and 85.9% after the forth
      one. The overall value for the diagnosis of T-cell lymphomas was 0.67 (good
      consensus) and for that of B-cell lymphomas was 1.00 (absolute consensus). The
      results of our study show that cutaneous lymphomas can be diagnosed reliably
      basing on the overall assessment of the clinical, histopathological, and
      immunohistochemical data. In some cases, however, molecular biologic methods may
      be required to diagnose cutaneous lymphomas properly.

PMID- 15154376
TI  - [Retrospective diagnosis of radiation inhalation lesions of the bronchial mucosa
      in clean-up personnel after the nuclear accident at the Chernobyl nuclear reactor
      using the micronucleus test].
AB  - The aim of the study was to detect radiation lesions in histological samples of
      bronchial mucosa in Chernobyl wreckers suffering from chronic non-obstructive
      bronchitis 10 years after Chernobyl accident by the micronuclear test. The study
      group consisting of Chernobyl wreckers was comparable to the controls by sex,
      age, smoking and morphological variants of chronic bronchitis. The test in the
      study group was positive as it showed a significant increase in the number of the
      ciliated cells in bronchial mucosa as compared to the control group. This
      suggests a long-term persistence of the radionuclides in the wreckers' bronchial
      mucosa. The micronuclear test is recommended for diagnosis of inhalation damage
      to the lungs in persons exposed to radiation.

PMID- 15154377
TI  - [Morphological changes in testicular tissue in clean-up personnel after the
      Chernobyl nuclear reactor accident].
AB  - Pathomorphological alterations of testicular tissue were absent in men exposed to
      total body ionizing radiation in the dose of 1 to 10 cGy. Some changes in
      seminiferous tubules appeared in the dose of 10 to 20 cGy. Lymphoid infiltration
      of the seminiferous tubules arose 5 years after the accident and of the
      interstitial tissue--10-15 years after the radiation in exposure in the dose 20
      30 cGy. Autoimmune orchitis affects spermatogenesis early after irradiation.
      Lymphoid infiltration of the seminiferous tubules and interstitial tissue is
      observed 5 years after radiation in the dose 30 to 50 cGy. Sclerosis of 50%
      seminiferous tubules, foci of regeneration of Leydig cells with lymphoid
      infiltration and interstitial fibrosis takes place 10-15 years after irradiation.

PMID- 15154378
TI  - [Embryonic mechanisms in development of spina bifida in humans].
AB  - The study of 86 human embryos and fetuses beginning from 23rdday of development
      up to 18th week after fecundation has detected 23 cases of pathologic development
      which correspond to the modern definition of spina bifida (SB). It is shown that
      the cause of various forms of the anomaly is the disturbance or temporary delay
      of a movement of caudal neurulation wave forming the spinal cord. The anomaly
      size and type are determined by the time and duration of a pathogenic action on
      neurulation. Postnatal or the 1st type of SB develops in neurulation wave
      disturbance not longer than 4-6 hours. Anomaly consequence may be compensated
      surgically. The 2nd or fetal type of SB arises when neurulation delay is from 6
      to 20 hours. If the delay occurs on the 22-24th day of development, embryos die
      by the neurulation end. If the delay takes place on the 26-28th day embryos may
      survive till the late fetal period. In embryonal or type III of SB embryos die by
      the end of the 8th week and do not enter the medical statistics. Their death is
      associated with delayed movement of the caudal neurulation wave for 24 hours and
      longer. This results in a spontaneous abortion.

PMID- 15154379
TI  - [Morphology of tissue reactions around implants after combined surgical repair of
      the abdominal wall].
AB  - Tissue reactions to titanium-nickelide and polypropylen and caprone implants used
      in surgical treatment of anterior aldomen wall hernias were studied in
      experiment. Digital density of leukocytes, fibroblasts, vessels, thickness of the
      capsule were studied. Pronounced inflammatory reaction was observed on day 3
      which attenuated on day 14 in case of titanium nickelide and on day 30-60 in case
      of polypropylene and caprone. Fibroplastic processes start in the first group
      after 7 days while in the second group only after 30 days of the experiment.
      Thickness of the capsule around titanium-nickelide was 2-3 times less than around
      polypropylene and caprone. Thus, titanium-nickelide material is biologically more
      inert than caprone and polypropylen which are widely used in surgery of hernias.

PMID- 15154380
TI  - [Paleopathology of Ichthyopterygia].
AB  - During microscopic histological studies of ichthyosaur bones the authors found
      that the bones of young ichthyosauri are well preserved without signs of
      inflammation. In the bones of old animals reproductive reactions were present.
      Thus, the severity of pathological alterations most likely depends on the age of
      the animals.

PMID- 15154381
TI  - Immunohistochemical studies in the differential diagnosis of small round cell
      soft tissue tumors.
AB  - In this review the authors focus on the differential diagnosis of small round
      cell tumors of soft tissue origin, giving emphasis on their specific
      immunohistochemical profiles. The sources of diagnostic errors and
      misinterpretations of the results of immunohistochemical staining are discussed
      in detail. It is thorough knowledge of specific characteristics of each tumor and
      appropriate interpretation of different staining techniques that will lead to
      precise classification of any given tumor, thus allowing accurate determination
      of prognosis and implementation of the optimal treatment.

PMID- 15154382
TI  - Gastrointestinal stromal tumors: update.
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of
      the gastrointestinal tract. GIST have characteristic morphological features and
      are positive for KIT (CD117). Overexpression of KIT in the tumor cells results
      from constitutive activation of the KIT tyrosine kinase receptor. KIT activation
      leads to intracellular signaling that causes increased cellular proliferation and
      enhanced cell survival leading to tumor formation. A successful therapeutic
      strategy is available with the pharmacological agent SCI.-571 that blocks the
      intracellular effects of KIT activation. GIST are more common in the stomach (60
      70%) and the small intestine (25-35%), with a minority of lesions occurring in
      the colon, rectum, appendix and esophagus. GIST differ histologically,
      immunohistochemically and genetically from leiomyomas, leiomyosarcomas and
      schwannomas. The pathologist plays an important role in the evaluation of these
      lesions. Adequate gross and microscopic pathological evaluation are crucial in
      the determination of treatment and prognosis.

PMID- 15154383
TI  - The testicular biopsy and spermatogenesis disturbance of infertile patients with
      bilateral varicocele.
AB  - In this article we describe the examination and the results obtained in 221
      patients subjected to surgical intervention, i.e. microsurgical bilateral
      varicocele or to the conventional Ivanisevich technique and systematic multiple
      and bilateral testicular biopsy at the scrotal examination. Testicular biopsy
      (TB) has been executed according to the microsurgical protocol in a standard way;
      in each of the testicles two different quadrants. Upper-internal and lower
      external quadrants were used to establish the qualitative mean index. According
      to concentration of spermatozoa per milliliter of the sperm the patients were
      classified into 5 different biological groups: I group--azoospermia or extreme
      oligozoospermia 93 patients, II--severe oligozoospermia 43 patients, III-
      moderate oligozoospermia 23, IV--relative oligozoospermia 18, and V group-
      normozoospermia 44 patients. The results of testicular biopsies have been
      evaluated according to the biological group. In the group with azoospermia and
      the extreme oligozoospermia the TB has determined the degree of the
      spermatogenesis derangement in 92 cases, in the majority of cases--50 MA
      (maturation arrest) + SCOS (Sertoli Cell Only Syndrome) + tubular fibrosis. In
      many cases hypospermatogenesis is accompanied with MA, SCOS or testicular
      fibrosis. In this group the semen analysis generally demonstrates different
      variations of oligospermia. Incidence of maturation arrest was observed in 32
      cases of total 221. Among the MA there are 7 cases of early stage spermatocyte I,
      MA spermatocyte II in 21 patients and MA spermatide (late arrest) in 4 cases.
      SCOS was observed in 20 patients. All the patients have secretory azoospermia.
      SCOS is also observed together with other disorders of spermatogenesis. Tubular
      and peritubular fibrose atrophy was observed in 5 cases. These are the patients
      with the antecedent criptorchidia.

PMID- 15154384
TI  - [Breast actinomycosis simulating lobular cancer in sectoral resection].
AB  - One case of breast actinomycosis in a 29-year-old woman is reported. Material of
      a sectoral resection was morphologically considered as a lobular infiltrative
      carcinoma. In surgically removed breast and regional lymph nodes granulomatous
      process with foci of suppuration and druses of actynomycetes were found.

PMID- 15154385
TI  - [Expert system for the diagnosis of thyroid neoplasms].
AB  - An original computer program designed to help in histological diagnosis of
      thyroid tumours is presented. The literature is given on the use of computer
      technologies in current morphology.

PMID- 15154386
TI  - [Chlamydia pneumoniae as a pathogenetic risk factor in the development of
      arteriosclerosis and its complications].
AB  - The literature data and the results of the authors' experiments allow one to
      consider Chlamydia pneumoniae as one of the leading risk factor of development of
      atherosclerosis and ischemic heart disease. Features of atherosclerosis
      morphogenesis in the presence of Chlamydia are described. Data, showing
      similarity of cell reactions, characterizing immune inflammation in mLDL deposit
      in arterial wall and obligate parasites are described. Synergism in the action of
      mLDL and chlamydial infection may induce a "malignant" course of atherogenesis
      promoting thrombosis and ischemic heart disease excerbation.

PMID- 15154387
TI  - [Care of handicapped children under general anaesthesia. Relationships with
      various clinical parameters. Preliminary notes].
AB  - Losses of teeth are significant and frequent among handicapped patients. For this
      study a sample of 58 children handicapped out of the 412 children dealt with for
      preserving dental care under general anaesthesia, was analyzed. If at equal age
      these children present a CAD on permanent teeth more significant, their
      undertake, the procedure of general anaesthesia and the preserving treatments
      under general anaesthesia do not present more difficulties than the child is
      handicapped or not. The factor determining in the effectiveness and the speed of
      the exempted acts seems to be the training of the dental care team.

PMID- 15154388
TI  - Cough and cold care kits reduce antibiotic use.

PMID- 15154389
TI  - Urgent need for new drugs in sub-Saharan Africa, says WMA president.

PMID- 15154390
TI  - [Importance of high intraabdominal pressure syndrome in surgical practice (review
      of the literature)].

PMID- 15154391
TI  - [Treatment of patients with vascular trauma in a big city].

PMID- 15154392
TI  - Impact of physical activity on medical expenditures among adults downhearted and
      blue.
AB  - OBJECTIVE: To examine inactivity-associated medical expenditures in adults,
      controlling for frequency of feeling downhearted/blue. METHODS: Using the 1987
      National Medical Expenditure Survey (N=12,250), expenditures were analyzed by
      comparison and multivariate models. Expenditures were updated to 2003 dollars.
      RESULTS: Medical expenditure was 354 dollars (t=3.80, P<0.01) lower for active
      than inactive persons: 6.1% of the expenditure (133 dollars in 1987, 429 dollars
      in 2003) was inactivity associated. The total inactivity-associated expenditure
      was near 12 billion dollars in 1987 (38 billion dollars in 2003). CONCLUSIONS:
      Medical expenditure increased with frequency of feeling downhearted/blue and was
      higher for inactive than active people.

PMID- 15154393
TI  - Bibliography of toxicology.

PMID- 15154394
TI  - [Therapy of systemic sclerosis].
AB  - The treatment of the patient with systemic sclerosis has greatly improved in the
      last ten years, because of two kinds of achievements. A number of drugs have been
      demonstrated to be active in some disease manifestations like alveolitis,
      pulmonary hypertension and complicated Raynaud's phenomenon. Some of these drugs
      namely cyclophosphamide and iloprost await to be confirmed as disease modifying
      agents. The methodological approach to be made in clinical trials has been
      defined allowing to correctly analyze the results of published trials and plan
      future ones.

PMID- 15154396
TI  - The effect of oral sucrose on exercise tolerance in patients with McArdle's
      disease.

PMID- 15154395
TI  - Evolutionary biology: lamprey Hox genes and the evolution of jaws.

PMID- 15154397
TI  - Current awareness in human psychopharmacology.

PMID- 15154398
TI  - Cross talk between iron metabolism and diabetes.

PMID- 15154399
TI  - Oxidative damage and schizophrenia: the potential benefit by atypical
      antipsychotics.
AB  - There is evidence to suggest the derangement of the oxidant and antioxidant
      defense system in schizophrenia. The present study examined the effect of
      atypical antipsychotics on lipid peroxidation, superoxide dismutase (SOD) and
      ascorbic acid. For this purpose, a prospective, open-label, 8-week study design
      was utilized. Serum SOD, serum malondialdehyde (MDA) and plasma ascorbic acid
      were estimated. Schizophrenic patients (n = 48) were compared with age- and sex
      matched healthy volunteers (n = 40). There was a significant increase in serum
      SOD, serum MDA and a decrease in plasma ascorbic acid in schizophrenic patients
      as compared to control subjects. The trend altered significantly after the
      treatment with atypical antipsychotics. The results of the Brief Psychiatric
      Rating Scale for schizophrenia also improved with the treatment. The findings
      indicate an involvement of free radicals in schizophrenia and its modification by
      treatment with atypical antipsychotics. This study can also be used as a
      predictor of drug response by atypical antipsychotics in schizophrenia.

PMID- 15154400
TI  - TRICARE Program; inclusion of anesthesiologist assistants as authorized
      providers; coverage of cardiac rehabilitation in freestanding cardiac
      rehabilitation facilities. Final rule.
AB  - This final rule establishes a new category of provider as an authorized TRICARE
      provider and it increases the settings where cardiac rehabilitation can be
      covered as a TRICARE benefit. It recognizes anesthesiologist assistants (AAs) as
      authorized providers under certain circumstances. It also authorizes cardiac
      rehabilitation services, which are already a covered TRICARE benefit when
      provided by hospitals, to be provided in freestanding cardiac rehabilitation
      facilities.

PMID- 15154401
TI  - Re: Position of the distal fibular fragment in pronation and supination ankle
      fractures: a CT evaluation, Tan, CW, et al., Foot Ankle Int. 24(7):561-566, 2003.

PMID- 15154402
TI  - Re: The relationship of the position of the metatarsal heads and peak plantar
      pressure, Weijers, RE, et al., Foot Ankle Int. 24(4):349-353, 2003.

PMID- 15154403
TI  - Experimental avoidance and high-risk sexual behavior in survivors of child sexual
      abuse.
AB  - While many long-term correlates of child sexual abuse (CSA) have been identified,
      theories to explain the development of these correlates have received little
      empirical validation. The process of experiential avoidance is one theory that
      has been proposed to account for many of the correlates of CSA. The purpose of
      the current study was twofold: (1) To attempt to develop a more complex measure
      of experiential avoidance in women with and without a CSA history, and (2) to
      explore variables related to two of the long-term correlates of CSA, general
      psychological distress and high risk sexual behavior. Levels of current distress,
      high-risk sex, and experiential avoidance were examined in 257 undergraduate
      females (mean age 20.0) using self-report questionnaires. The results of the
      current study indicate that CSA survivors report higher levels of experiential
      avoidance and high-risk sexual behavior with persons other than their primary
      partners. Implications of these findings for theory development, therapy with CSA
      survivors, and HIV prevention programs are discussed.

PMID- 15154404
TI  - IQ predicts treatment response.

PMID- 15154405
TI  - Nevirapine warning.

PMID- 15154406
TI  - Nevirapine may promote resistance.

PMID- 15154407
TI  - Schering D data look promising.

PMID- 15154409
TI  - Women urged to get screening.

PMID- 15154408
TI  - Rite of passage? Why young adults become uninsured and how new policies can help.
AB  - Young adults (ages 19 to 29) are one of the largest and fastest-growing segments
      of the population without health insurance in the United States. Young adults
      often lose coverage under their parents' policies at age 19, or when they
      graduate from high school or college. Nearly two of five college graduates and
      one-half of high school graduates who do not go on to college will endure a time
      without health insurance in the first year after graduation. Three policy changes
      could extend coverage to uninsured young adults and prevent others from losing
      coverage: extending eligibility for dependents under private coverage through age
      23; extending eligibility for Medicaid/CHIP public coverage to age 23; and
      ensuring that colleges and universities require full-time and part-time students
      to have insurance, and that they offer coverage to both. Young adults are a
      relatively low-cost population to insure, and keeping them in insurance pools may
      lower the average costs of group coverage.

PMID- 15154410
TI  - Sex-Ed play in California.

PMID- 15154412
TI  - New York City has higher infection rate.

PMID- 15154411
TI  - Blacks urged to  participate in trials.

PMID- 15154413
TI  - Vaccine news is disappointing.

PMID- 15154414
TI  - [Ximelagatran (Exanta). Laboratory: Astra Zeneca].

PMID- 15154415
TI  - Appreciation. Dr. Norman Heatley.

PMID- 15154416
TI  - The cost of privatization: extra payments to Medicare Advantage plans.
AB  - The recently enacted Medicare Prescription Drug, Improvement, and Modernization
      Act of 2003 (MMA) includes a broad set of provisions intended to enlarge the role
      of private health plans (called Medicare Advantage plans) in Medicare. This issue
      brief examines the payments that private plans are receiving in 2004 relative to
      costs in traditional fee-for-service Medicare, using data from the 2004 Medicare
      Advantage Rate Calculation Data spreadsheet. The authors find that, for 2004,
      Medicare Advantage payments will average 8.4 percent more than costs in
      traditional fee-for-service Medicare: $552 for each of the 5 million Medicare
      enrollees in managed care, for a total of more than $2.75 billion. In some
      counties, extra payments by Medicare are more than double this amount. Although
      the stated objective of efforts to increase enrollment in private plans is to
      lower costs, the policies of MMA regarding private plans explicitly increase
      Medicare costs in 2004 and through 2013.

PMID- 15154417
TI  - [The 80th anniversary of N. V. Sklifosovskii Research Institute of Emergency
      Care].

PMID- 15154418
TI  - [Guideline of catheter interventional therapy for congenital heart diseases].

PMID- 15154419
TI  - Going the extra mile: a  new life for Darwin.

PMID- 15154420
TI  - The fountain of mental youth. Search for homeostatic and adaptational hormonal
      processes.
AB  - Successful mental aging may be defined as maintenance of youthful attitudes,
      cognitive and adaptational processes despite advanced age. Maintenance of
      homeostasis and efficient adaptational processes are of utmost importance. It is
      suggested that multiple hormonal systems and processes are involved in the
      multidimensional, interdependent, interrelated successful aging process. Changes
      in their interactions over time probably occur. A complex integrated regulatory
      homeostatic and normalcy system is proposed. Disruption on this regulating
      normalization process may cause disorders, as well as accelerated mental aging.
      Currently not much is known about maintenance of mental normalcy, as well as
      homeostatic and adaptational underlying mechanisms. Their elucidation would
      substantially contribute to understanding of well-being, disorders, and
      successful as well as unsuccessful aging.

PMID- 15154421
TI  - Euthanasia: an introduction.
AB  - It has been argued that euthanasia is one of the most pressing social concerns of
      our times. A review of current scientific and legal materials, however, indicates
      that this issue is a complex and contentious one that crosses numerous
      perspectives and theoretical orientations. In order to provide background for the
      other articles in this collection, we present a brief history of attitudes toward
      euthanasia. In addition, various terms that are associated with the concept of
      euthanasia are defined. Finally, this paper provides a framework for the articles
      that follow by suggesting that three central issues must be addressed in order to
      resolve the controversies surrounding euthanasia. These are (1) the establishment
      of standardized criteria of euthanasia eligibility, (2) the investigation of
      public attitudes regarding acceptable means for engaging in euthanasia, and (3)
      the evaluation of the roles of professionals who are directly involved in
      euthanasia decisions. We hope that the following articles will provide insight
      into these issues.

PMID- 15154422
TI  - The problem of inadequately relieved suffering.
AB  - A request for euthanasia or assistance in suicide usually derives from severe
      patient distress and indicates significant suffering. Although the Hippocratic
      purview of medicine requires that suffering be acknowledged, its causes be
      identified, and that steps be taken to provide adequate relief, an appreciation
      of the diversity of factors that may contribute to suffering underscores the need
      for methodical assessment and familiarity with a range of therapeutic strategies.
      It may be argued that when other options to effectively relieve suffering are
      available, euthanasia and assisted suicide fall outside of the purview of
      Hippocratic medicine. Given the existence of other options, the capacity for
      human maleficence, and the lack of resources currently allocated to the relief of
      suffering, this paper presents a number of reservations regarding the
      legalization of euthanasia and assisted suicide. In addition, it is suggested
      that the current community focus on the issue of inadequately relieved suffering
      should be harnessed to work toward the provision of care that would diminish the
      impression that elective death is necessary to ensure adequate relief.

PMID- 15154423
TI  - Fixed-point observation of Oncomelania nosophora in Kofu Basin -- establishment
      of monitoring system of schistosomiasis japonica in Japan.
AB  - There are still many Oncomelania snails that inhabit the Kofu Basin, Yamanashi
      Prefecture, Japan, which had been declared free of schistosomiasis japonica. Due
      to the need to monitor the situation, a fixed-point observation system using GIS
      from GPS is being examined. In addition, in broad present or former endemic
      areas, survey areas are being managed by remote sensing with satellite images or
      aerial photographs. A simple and effective monitoring method by mobile GIS using
      PDAs was developed, risk or hazard maps were prepared and a system that would
      enable a response in the event of reemergence is being examined.

PMID- 15154424
TI  - [Prevention of senile dementia].

PMID- 15154425
TI  - [Suggestions for solving problems in long-term care insurance in Japan].

PMID- 15154426
TI  - [Present status of and tasks in guardianship for the mentally incompetent aged].

PMID- 15154427
TI  - [Early-rearing experience and environment as etiological factors for adult-onset
      depressive disorder].

PMID- 15154428
TI  - [Diagnosis of mild cognitive impairment].

PMID- 15154429
TI  - [Link between biologic psychiatry and psychiatric pathology].

PMID- 15154430
TI  - [Diagnosis of and therapy for patients with alcoholism].

PMID- 15154431
TI  - A geometric model of mortality and crop protection for insects feeding on
      discrete toxicant deposits.
AB  - Current theory governing the biological effectiveness of toxicants stresses the
      dose-response relationship and focuses on uniform toxicant distributions in the
      insect's environment. However, toxicants are seldom uniformly dispersed under
      field conditions. Toxicant distribution affects bioavailability, but the
      mechanics of such interactions is not well documented. We present a geometric
      model of the interactions between insects and heterogeneously distributed
      toxicants. From the model, we conclude the following: 1) There is an optimal
      droplet size, and droplets both smaller and larger than this optimum will
      decrease efficacy. 2) There is an ideal droplet distribution. Droplets should be
      spaced based on two criteria: calculate the allowable damage, double this
      quantity, and one lethal deposit should be placed in this area; and define the
      quantity of leaf the larva could eat before the toxicant decays below the lethal
      level and place one lethal deposit within this area. 3) Distributions of toxicant
      where deposits are sublethal will often be ineffective, but the application is
      wasteful if deposits contain more than a lethal dose. 4) Insect behavior both as
      individuals and collectively influences the level of crop production provided by
      an application. This conclusion has implications for both crop protection and
      natural plant-insect interactions. The effective utilization of new more
      environmentally sensitive toxicants may depend on how well we understand how
      heterogeneous toxicant distributions interact with insect behavior to determine
      the biological outcome.

PMID- 15154432
TI  - Honey bee (Hymenoptera: Apidae) distribution and potential for supplementary
      pollination in commercial tomato greenhouses during winter.
AB  - This study examined the use of honey bees, Apis mellifera L., to supplement
      bumble bee, Bombus spp., pollination in commercial tomato, Lycopersicon
      esculentum Miller, greenhouses in Western Canada. Honey bee colonies were brought
      into greenhouses already containing bumble bees and left for 1 wk to acclimatize.
      The following week, counts of honey and bumble bees foraging and flying
      throughout the greenhouse were conducted three times per day, and tomato flowers
      open during honey bee pollination were marked for later fruit harvest. The same
      counts and flower-marking also were done before and after the presence of honey
      bees to determine the background level of bumble bee pollination. Overall, tomato
      size was not affected by the addition of honey bees, but in one greenhouse
      significantly larger tomatoes were produced with honey bees present compared with
      bumble bees alone. In that greenhouse, honey bee foraging was greater than in the
      other greenhouses. Honey bees generally foraged within 100 m of their colony in
      all greenhouses. Our study invites further research to examine the use of honey
      bees with reduced levels of bumble bees, or as sole pollinators of greenhouse
      tomatoes. We also make specific recommendations for how honey bees can best be
      managed in greenhouses.

PMID- 15154433
TI  - Larval Apis mellifera L. (Hymenoptera: Apidae) mortality after topical
      application of antibiotics and dusts.
AB  - Beekeepers apply various dusts to honey bee, Apis mellifera L., colonies to
      dislodge parasitic mites and control bacterial brood diseases. Anecdotal reports
      by beekeepers indicate that the antibiotic oxytetracycline (OTC) can be toxic
      when applied in powdered sugar to cells containing immature bee brood, but it was
      not known whether the purported toxicity is caused by the antibiotic or the sugar
      carrier. Additionally, the toxicity of various dusts, proposed for parasitic mite
      control, is poorly known. In the current studies, we tested OTC and two other
      antibiotics (tylosin and lincomycin, candidate compounds for use in honey bee
      colonies) in a powdered sugar carrier for larval toxicity. We also tested for
      larval toxicity, several dusts that have been proposed for mite control. OTC
      caused significant brood mortality of approximately 80% at the concentrations
      used in the hive (200 mg in 20 g sugar). In contrast, tylosin and lincomycin at
      the 200 mg dose were both similar to untreated controls, and only five times that
      concentration (1000 mg) caused significant brood mortality of approximately 65%.
      The addition of dusts, wheat flour, talc, and a commercially available protein
      supplement, BeePro, resulted in mortality levels between 65 and 80%, similar to
      that seen with OTC. The common antibiotic carrier, powered confectioners sugar,
      was nontoxic. The use of 100 unsealed brood cells was demonstrated to be a
      reliable means of assessing potential adverse affects of dry compounds on larval
      honey bees. Two new candidate antibiotics for use in honey bee colonies were less
      toxic to larval bees than the currently labeled antibiotic, OTC.

PMID- 15154434
TI  - Indoor winter fumigation of Apis mellifera (Hymenoptera: Apidae) colonies
      infested with Varroa destructor (Acari: Varroidae) with formic acid is a
      potential control alternative in northern climates.
AB  - Formic acid treatment for the control of the ectoparasitic varroa mite, Varroa
      destructor Anderson & Trueman, infesting honey bee, Apis mellifera L., colonies
      is usually carried out as an in-hive outdoor treatment. This study examined the
      use of formic acid on wintered colonies kept indoors at 5 degrees C from 24
      November 1999 to 24 March 2000. Colonies were placed in small treatment rooms
      that were not treated (control) or fumigated at three different concentrations of
      formic acid: low (mean 11.9 +/- 1.2 ppm), medium (mean 25.8 +/- 1.4 ppm), or high
      (mean 41.2 +/- 3.3 ppm), for 48 h on 22-24 January 2000. Queen bee, worker bee,
      and varroa mite mortality were monitored throughout the winter, and tracheal
      mite, Acarapis woodi (Rennie), prevalence and mean abundance of nosema, Nosema
      apis Zander, spores were assessed. This study revealed that formic acid
      fumigation of indoor-wintered honey bees is feasible and effective. The highest
      concentration significantly reduced the mean abundance of varroa mites and nosema
      spores without increasing bee mortality. Tracheal mite prevalence did not change
      significantly at any concentration, although we did not measure mortality
      directly. The highest concentration treatment killed 33.3% of queens compared
      with 4.8% loss in the control. Repeated fumigation periods at high concentrations
      or extended fumigation at low concentrations may increase the efficacy of this
      treatment method and should be tested in future studies. An understanding of the
      cause of queen loss and methods to prevent it must be developed for this method
      to be generally accepted.

PMID- 15154435
TI  - Comparison between two thymol formulations in the control of Varroa destructor:
      effectiveness, persistence, and residues.
AB  - An apiary trial on the use of two acaricide formulations (gel-Apiguard and
      vermiculite and Api Life VAR) in the control of Varroa destructor (Anderson &
      Trueman) was conducted in summer 2001 in Sardinia (Italy). The main goals were 1)
      to determine their effectiveness against V. destructor, taking into account
      natural mite mortality in control hives; and simultaneously 2) to determine the
      persistence of both formulations and residues in honey and wax, by using a new
      extraction method. Both thymol formulations, after the treatments, reduced
      significantly the levels of mite infestations of adult bees and sealed brood, but
      their efficacy, expressed as percentage of mortality, was lower for both products
      (Api Life VAR 74.8 +/- 13.1 and 81.3 +/- 15.5, Apiguard 90.4 +/- 8.3 and 95.5 +/-
      8.7 for sealed brood and adult bees, respectively) than the efficacy previously
      obtained with the same products in other experimental conditions. Moreover, a
      considerable colony-to-colony variability was recorded, and a significant
      negative effect of the thymol treatments on colony development was observed.
      During 2 wk of treatment, the bees removed nearly 95% of all the applied product
      (gel or vermiculite). Residues found in honey collected from the nest varied from
      0.12 to 4.03 mg/kg for Api Life VAR and from 0.40 to 8.80 mg/kg for Apiguard. The
      residues were relatively higher in wax (Api Life VAR = 21.6 +/- 13.0; Apiguard =
      147.7 +/- 188.9) than in honey, because thymol is a fat-soluble ingredient.

PMID- 15154437
TI  - Life history of the bird cherry-oat aphid, Rhopalosiphum padi (Homoptera:
      Aphididae), on transgenic and untransformed wheat challenged with barley yellow
      dwarf virus.
AB  - The life history of Rhopalosiphum padi (L.) was monitored on transgenic and
      untransformed (soft white winter wheat plants that were infected with Barley
      yellow dwarf virus (BLDV), noninfected, or challenged with virus-free aphids
      under laboratory conditions. Two transgenic soft white winter wheat genotypes
      (103.1J and 126.02) derived from the parental variety Lambert and expressing the
      barley yellow dwarf virus coat protein gene, and two untransformed varieties,
      virus-susceptible Lambert and virus-tolerant Caldwell, were tested. B. padi
      nymphal development was significantly longer on the transgenic genotypes infected
      with BYDV, compared with noninfected transgenic plants. In contrast, nymphal
      development on Lambert was significantly shorter on BYDV-infected than on
      noninfected plants. Nymphal development on noninfected Lambert was significantly
      longer than on noninfected transgenics. No significant difference in nymphal
      development period was detected between virus-infected and noninfected Caldwell.
      Aphid total fecundity, length of reproductive period, and intrinsic rate of
      increase were significantly reduced on BYDV-infected transgenic plants compared
      with BYDV-infected Lambert. In contrast, reproductive period, total adult
      fecundity, and intrinsic rate of increase on noninfected Lambert were
      significantly reduced compared with noninfected transgenics. Transgenic plants
      infected with BYDV were inferior hosts for R. padi compared with infected
      Lambert. However, noninfected transgenics were superior hosts for aphids than
      noninfected Lambert. Moderate resistance to BYDV, as indicated by a significantly
      lower virus titer, was detected in the transgenic genotypes compared with the
      untransformed ones. Results show for the first time that transgenic virus
      resistance in wheat can indirectly influence R. padi life history.

PMID- 15154438
TI  - Effects of cold storage on field and laboratory performance of Trichogramma
      carverae (Hymenoptera: Trichogrammatidae) and the response of three Trichogramma
      spp. (T. carverae, T. nr. brassicae, and T. funiculatum) to cold.
AB  - Delaying emergence of Trichogramma spp. is critical for commercial production.
      Here, diapause induction was considered for three species (Trichogramma nr.
      brassicae Bezdenko, Trichogramma carverae Oatman & Pinto, and Trichogramma
      funiculatum Carver), and the effect of storage temperature (4 degrees C, 8
      degrees C, and 10 degrees C) and time (1-8 wk) was investigated for T. carverae.
      For all species, percentage of emergence was lowered after an initial diapause
      induction period (28 d at 14 degrees C and a photoperiod of 8:16 [L:D] h) and
      lowered further after 1-mo storage at 3 degrees C and a photoperiod of 0:24 (L:D)
      h. No wasps emerged after 2 mo of storage, suggesting that true diapause was not
      induced. The effect of 1-8-wk storage on wasp quality was investigated for T.
      carverae both in the laboratory and the field. Initial fieldwork suggested that
      this species could be successfully stored at 10 degrees C under continuous light
      (after 5-d development at 25 degrees C and a photoperiod of 16:8 [L:D] h) without
      reducing the ability of wasps to parasitize eggs in the field. In a second
      experiment, storage temperatures lower than 10 degrees C and storage times 3 wk
      or longer had a negative impact on emergence and longevity, and effects were not
      additive. Negative effects may partly reflect size changes, because size
      decreased in response to storage time, and there was an interaction between time
      and temperature effects on size. Storage time was the major factor influencing
      fecundity and field success; both fitness measures were reduced after storage of
      3 wk or longer. T. carverae can therefore be successfully stored for up to 2 wk
      without detrimental effects, and 10 degrees C is the preferred storage
      temperature. T. carverae seems to survive unfavorable temperature conditions by
      entering a state of quiescence.

PMID- 15154436
TI  - Bean leaf beetle (Coleoptera: Chrysomelidae) management for reduction of bean pod
      mottle virus.
AB  - Bean pod mottle virus (BPMV) is a management concern for soybean, Glycine max
      (L.), producers in the North Central states because it can cause yield loss and
      reduce seed quality by induction of seed coat mottling. The main vector of BPMV
      is the bean leaf beetle, Cerotoma trifurcata (Forster). An experiment was
      conducted in 2000 and 2001 at two locations in northwestern and central Iowa to
      test three insecticide treatments for suppression of bean leaf beetles, and
      subsequently, BPMV. Treatments of insecticide applications with lambda
      cyhalothrin were 1) a single early-season application (23 g [AI] /ha) (2.5
      oz/acre) at the VE-VC soybean developmental stage; 2) two early-season
      applications, the first the same as treatment 1 and a second at the same rate 9
      13 d later; 3) a single early-season application the same as treatment 1,
      followed by a mid-season application (28 g [AI] /ha (3.2 oz/acre) at
      approximately R2 (flowering, near 15 July); and 4) an unsprayed control.
      Application of lambda-cyhalothrin after soybean emergence and again as first
      generation bean leaf beetles emerged in northwestern Iowa in 2000 (treatment 3)
      significantly reduced beetle densities through mid-season, BPMV field incidence
      by 31.5%, and seed coat mottling by 31.2%, compared with the unsprayed control.
      Similar effects were measured at the same location when insecticide was applied
      twice at early season (treatment 2). Yield was 453.7 kg/ha (6.74 bu/acre) greater
      in treatment 2 and 525.20 kg/ha (7.80 bu/acre) greater in treatment 3 than in the
      unsprayed control at the northwestern site in 2000. At both locations in 2001
      fewer treatment effects were observed, which was likely related to lower beetle
      populations in that year. Early-season insecticide sprays targeted at
      overwintered beetles on VC-VE reduced the initial population of vector insects
      and may have contributed to a lower first-generation population because of
      reduced overwintered beetle oviposition. In 1 year at one location there was a
      benefit to an additional mid-season insecticide spray, although effectiveness of
      spraying at this time could vary based on the magnitude of the vector population.

PMID- 15154439
TI  - Effect of the red imported fire ant on cotton aphid population density and
      predation of bollworm and beet armyworm eggs.
AB  - The effects of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera:
      Formicidae), on cotton aphid, Aphis gossypii Glover, populations and its
      predation of bollworm, Helicoverpa zea (Boddie), and beet armyworm, Spodoptera
      exigua (Hubner), (both Lepidoptera: Noctuidae) eggs were evaluated in cotton
      under field conditions during 2001 and 2002 in central and northern Texas. In
      central Texas, cotton aphid populations were approximately 5.5 times greater and
      predation of sentinel bollworm eggs 2 times greater in the presence of S. invicta
      versus in its absence, although aphid populations did not reach economic levels.
      Most predation of beet armyworm egg masses, measured via direct nocturnal
      observations, was due to S. invicta (68%) and cotton fleahopper, Pseudatomoscelis
      seriatus (Reuter) (21%), where S. invicta was present, and by the mite Abrolophus
      sp. (52%), spiders (13%), and minute pirate bug (Orius sp.) (13%) where S.
      invicta was absent. Predation of sentinel bollworm eggs and beet armyworm egg
      masses was approximately 1.5 and 4.1 times greater, respectively, in the presence
      of S. invicta versus in their absence. In the presence of S. invicta, the
      relative frequencies of minute pirate bug and cotton fleahopper were higher, and
      of S. invicta and native ants lower in beat bucket samples compared with their
      relative frequencies in nocturnal observations of predation upon beet armyworm
      egg masses. In the absence of S. invicta seven of eight predators sampled were
      similarly represented in beat bucket samples and nocturnal observations of beet
      armyworm egg mass predation, whereas minute pirate bug occurred at a higher
      frequency in beat bucket samples relative to nocturnal observations. These
      observations suggested that the relative frequencies of minute pirate bug, cotton
      fleahopper, S. invicta and native ants in beat bucket samples do not closely
      reflect the frequency with which these predators prey on noctuid eggs. Overall,
      the results of this study show that although S. invicta may promote aphid
      populations early in the growing season, it is an important predator of bollworm
      and beet armyworm eggs later in the season.

PMID- 15154440
TI  - Predation by cosmopolitan spiders upon the medically significant pest species
      Loxosceles reclusa (Araneae: Sicariidae): limited possibilities for biological
      control.
AB  - Interspecific predation of three cosmopolitan house spiders, Achearanea
      tepidariorum (Kock 1841) (Theridiidae), Steotoda triangulosa (Walckenaer 1802)
      (Theridiidae), and Pholcus phalangioides (Doleschall 1859) (Pholcidae), and the
      medically significant brown recluse spider, Loxosceles reclusa (Sicariidae) were
      examined to evaluate transitive predatory relationships and to explore the
      potential use of cosmopolitan spiders as effective biological control agents on
      L. reclusa. Fifty houses from northeastern Kansas were visually inspected from
      May to December 2002 for cosmopolitan spiders and L. reclusa. In 25 houses,
      insect monitoring traps were used to sample spider diversity and abundance. The
      remaining 25 houses were monitored to examine intraguild predation and spider
      behavior. If cosmopolitan spiders have the ability to regulate or decrease L.
      reclusa populations, houses with large cosmopolitan spider populations are
      expected to have significantly fewer L. reclusa than houses without cosmopolitan
      spiders. Predation and/or evidence of predation by all three cosmopolitan spiders
      on L. reclusa was detected in 68% of houses. Spearman's rank correlation analysis
      showed overall positive relationships between population densities of
      cosmopolitan spiders and L. reclusa. When evaluated independently, the presence
      of both A. tepidariorum and S. triangulosa showed negative, yet nonsignificant,
      relationships with L. reclusa densities, whereas P. phalangioides showed a
      positive nonsignificant relationship. Although statistical tests showed a
      decrease in L. reclusa population densities with increased population densities
      of two cosmopolitan species, alluding to a potential beneficial interaction for
      biological control, observations of spider behavior, web positioning (niche
      partitioning), and predation showed little possibility of biological control
      capabilities.

PMID- 15154441
TI  - Influence of antimicrobial agents on the spoilage of a meat-based entomophage
      diet.
AB  - The microbial decomposition of a meat-based entomophage diet presented in
      Parafilm packets was investigated. Considerable bacteria but not fungi were
      associated with components used to prepare the diet (i.e., hens' eggs, liver, and
      ground beef). At the initial sampling time, there were no differences among diet
      treatments in the size of bacterial or fungal populations. Bacterial populations
      in diets not containing antibacterial agents rapidly increased and reached an
      asymptote by 24 h (approximately 10(10) colony-forming units per gram). Bacterial
      populations also increased in diets containing antibacterial agents, but they
      were significantly smaller than in diets not containing antibacterial agents. The
      most prevalent bacteria isolated were Carnobacterium piscicola, Carnobacterium
      divergens, Lactobacillus curvatus, Lactobacillus sakei, Leuconostoc
      mesenteroides, and Enterococcus spp., regardless of the antibacterial treatment
      used. The proliferation of fungi was delayed relative to bacteria, but
      significant differences were observed among the diet treatments. Fungi were most
      inhibited by sorbic acid and propionic acid in the absence of antibacterial
      agents. The most common fungi isolated were the yeasts Candida zeylanoides,
      Torulaspora globosa, and Yarrowia lipolytica. The pH of diets not containing
      antibacterial agents decreased rapidly and was highly correlated with increases
      in bacteria but not fungi. The results of this study demonstrate that
      antimicrobial agents significantly inhibit spoilage microorganisms in a meat
      based diet and that alternative management strategies to delay the decomposition
      of such diets presented in Parafilm packets should target lactic acid spoilage
      bacteria, particularly Carnobacterium and Lactobacillus species.

PMID- 15154442
TI  - Screening of the insecticidal activity of Bacillus thuringiensis strains against
      Lygus hesperus (Hemiptera: Miridae) nymphal population.
AB  - Lygus hesperus Knight (Hemiptera: Miridae) is an economically important insect
      pest controlled primarily by chemical pesticides. Bacillus thuringiensis Berliner
      is a gram-positive bacterium that has been developed for the control of some
      insect pests in the orders Lepidoptera, Coleoptera, and Diptera. In this study,
      whole culture extracts of 94 B. thuringiensis strains from 83 serovars were added
      to an artificial diet and assayed against L. hesperus first and second instars. A
      total of five B. thuringiensis strains, B. thuringiensis variety thuringiensis,
      thuringiensis exotoxin +, morrisoni, tolworthi, and darmstadiensis generated >
      98% mortality after 7 d of incubation. The screening was repeated with 117 alkali
      solubilized trypsin-digested B. thuringiensis cultures and the same five B.
      thuringiensis strains showed nearly identical results. All five strains produce
      beta-exotoxin, which exhibits a wide host spectrum activity. No beta-exotoxin
      minus B. thuringiensis strains showed significant toxicity against L. hesperus
      nymphs. The present work is one of the first thorough screenings of the wide
      diversity of the B. thuringiensis varieties for the control of L. hesperus
      nymphal populations.

PMID- 15154443
TI  - Assessment of experimental Bt events against fall armyworm and corn earworm in
      field corn.
AB  - Performance of experimental Bacillus thuringiensis (Bt) MON events alone and
      pyramided with MON810 were evaluated over 3 yr in Georgia and Alabama. Ability of
      events to prevent whorl defoliation by the fall armyworm, Spodoptera frugiperda
      (J. E. Smith), and natural ear feeding damage by the corn earworm, Helicoverpa
      zea (Boddie) was assessed. In each year, near-isogenic hybrids with novel single
      transformation events and crosses pyramided with the MON810 event were compared
      with the standard single MON810 event and nontransformed susceptible control.
      Events were tested for resistance to whorl damage by manual infestations of fall
      armyworm and ear damage by natural infestations of corn earworm. All Bt events
      tested reduced fall armyworm whorl damage ratings per plant compared with the
      susceptible hybrid. All Bt treatments also had considerably less ear infestation
      and damage by corn earworm compared with the nontransgenic isoline. The MON841,
      MION849, and MON851 events reduced ear damage by H. zea but were not as effective
      as other novel events and were not advanced for further testing after the 1999
      season. Pyramiding events compared with single events did not improve control of
      fall armyworm whorl damage, but they generally did prevent more ear damage by
      corn earworm. The MON84006 event singly and pyramided with MON810 had superior
      control of whorl-stage damage by S. frugiperda and ear damage by H. zea compared
      with MON810. Deployment of new events and genes could provide additional tools
      for managing the potential for insect resistance to Bt toxins. Furthermore,
      improved control of whorl and ear infestations by H. zea and S. frugiperda would
      increase the flexibility of planting corn, Zea mays L., and permit double
      cropping of corn in areas where these pests perennially reach damaging levels.

PMID- 15154445
TI  - Diatomaceous earth increases the efficacy of Beauveria bassiana against Tribolium
      castaneum larvae and increases conidia attachment.
AB  - This research tested the suppressive ability of Beauveria bassiana (Balsamo)
      Vuillemin alone and in combination with diatomaceous earth against the red flour
      beetle, Tribolium castaneum (Herbst). Adults did not show a dose response to B.
      bassiana, and the addition of diatomaceous earth (DE) did not result in a
      significant increase in mortality. Against larvae, however, DE at 190 mg/kg grain
      enhanced the efficacy of B. bassiana at all concentrations ranging from 33 to
      2,700 mg of conidia per kilogram of grain. The presence of DE resulted in 17- and
      16-fold decreases in the median lethal concentration of B. bassiana at 56 and 75%
      RH, respectively. No significant differences in larval mortality in response to
      B. bassiana and diatomaceous earth alone or in combination were found between 56
      and 75% RH. Conidial attachment to larvae was significantly greater with 190
      mg/kg DE than without it. The partial analysis of lipids taken up by DE from the
      larvae revealed the removal of phospholipids and long-chain fatty acids. These
      results support the hypothesis that diatomaceous earth enhances the efficacy of
      B. bassiana against larval T. castaneum, at least in part by damaging the insect
      cuticle, thus increasing conidial attachment and making nutrients more available
      to conidia for their germination.

PMID- 15154444
TI  - Deliberately added and "cryptic" antioxidants in three artificial diets for
      insects.
AB  - Characteristics of both deliberately added and "cryptic" antioxidants were
      assayed from hydrophilic and lipophilic extracts from artificial diets for plant
      bugs, lepidopteran larvae, and green lacewings. Cryptic antioxidants are defined
      as substances naturally existing in diet ingredients but not deliberately added
      because of their antioxidant potential. Diets were tested after 1) being freshly
      produced, 2) stored for 48 h at 4 degrees C, or 3) held for 48 h under rearing
      room conditions at 27 degrees C. Tests included 1) a general assay of antioxidant
      capacity known as the ferric-reducing antioxidant power (FRAP) assay. 2) a cation
      radical-scavenging assay, 3) an ascorbic acid assay, and 4) an assay of
      inhibition of lipid peroxidation. In all assays, the lepidopteran diet had the
      highest values for protection against reactive oxygen species (ROS). The
      lepidopteran diet (with 0.17-0.23-mg equivalents of gallic acid equals total
      phenolic compounds per gram of diet) had three- to four-fold higher
      concentrations of phenolic compounds than did either the plant bug diet or the
      lacewing diet. Unexpectedly, the plant bug and the lacewing diets caused more
      lipid peroxidation than did the positive controls. This was attributed to the
      high concentrations of iron in these diets (mainly from chicken eggs), causing an
      ascorbate-ferric ion-induced lipid peroxidation. Diet storage, measured after 2 d
      at 27 or 4-6 degrees C, caused no significant declines in overall antioxidant
      potential. However, storage did lead to decline in ascorbic acid. The FRAP assay
      offered the best potential as a general, routine test of the potential of various
      insect diets to resist the destructive effects of ROS. The importance of
      addressing issues of protection against ROS in insect diets is discussed.

PMID- 15154446
TI  - Toxicity of propylene oxide at low pressure against life stages of four species
      of stored product insects.
AB  - The relative toxicity of propylene oxide (PPO) at a low pressure of 100 mm Hg to
      four species of stored product insect at 30 degrees C over a 4-h exposure period
      was investigated. PPO at 100 mm Hg was toxic to all four species tested:
      Tribolium castaneum (Herbst), Plodia interpunctella (Hubner), Ephestia cautella
      (Wlk.), and Oryzaephilus surinamensis (L.). There were differences in
      susceptibility between the life stages of the tested insect species. Mortality
      tests on all life stages of the insects resulted in LD99 values ranging from 4.7
      to 26.1 mg/liter. The pupal stage of E. cautella, O. surinamensis, and T.
      castaneum was the most tolerant stage with LD99 values of 14.4, 26.1, and 25.7
      mg/liter, respectively. For P. interpunctella, the egg stage was most tolerant,
      with a LD99 value of 15.3 mg/liter. Generally, PPO at 100 mm Hg was more toxic to
      P. interpunctella and E. cautella than to O. surinamensis and T. castaneum. A 99%
      mortality of all life stages of the tested species was achieved at a
      concentrations x time product of 104.4 mg h/liter. These findings indicate that a
      combination of PPO with low pressure can render the fumigant a potential
      alternative to methyl bromide for rapid disinfestation of commodities.

PMID- 15154447
TI  - Irradiation of mangoes as a postharvest quarantine treatment for fruit flies
      (Diptera: Tephritidae).
AB  - Mangoes infested with third instar larvae were irradiated using Co-60 gamma rays
      and a dose interval of 2-250 Gy to assess the irradiation dose required to
      prevent adult emergence of the Mexican fruit fly (Anastrepha ludens), the West
      Indies fruit fly (A. obliqua), the sapote fruit fly (A. serpentina), and the
      Mediterranean fruit fly (Ceratitis capitata). Doses of 76.9, 87.3, 91.4 and 112.7
      Gy, were estimated to inhibit 99.9968% (probit 9) of adult emergence forA.
      obliqua, A. serpentina, A. ludens, and C. capitata, respectively. Using mangoes
      infested with a total of 100,000 larvae of each species, the results obtained in
      the laboratory were confirmed using a dose of 100 Gy for the Anastrepha species
      and 150 Gy for C. capitata. No adult emergence was observed for any of the four
      species compared with approximately 80% emergence in the controls. A dose of 150
      Gy is recommended as a generic quarantine treatment against potential infestation
      of these species in exported mangoes. A minor decrease in the ascorbic acid
      content was the only adverse effects observed in irradiated mangoes.

PMID- 15154448
TI  - Nonhost status of commercial Persea americana 'Hass' to Anastrepha ludens,
      Anastrepha obliqua, Anastrepha serpentina, and Anastrepha striata (Diptera:
      Tephritidae) in Mexico.
AB  - The objective of this study was to determine the host status in Mexico of
      commercially cultivated and marketed avocado, Persea americana (Mill.), 'Hass' to
      Anastrepha ludens (Loew), Anastrepha obliqua (Macquart), Anastrepha serpentina
      (Wiedemann), and Anastrepha striata (Schiner) (Diptera: Tephritidae). Experiments
      in Michoacan, Mexico, were carried out in six orchards located at three altitudes
      above sea level during two times (August-October 2001 and April-June 2002). They
      included choice ('Hass' avocado plus natural host) and no-choice foraging
      behavior tests on trees under field cages; no-choice, forced infestation trials
      on caged, fruit-bearing branches in the field, and with individual fruit under
      laboratory conditions; infestation trials using 'Hass' avocados left unprotected
      over 1 and 7 d on the ground of orchards; studies to ascertain depth of
      oviposition and determine egg hatchability; and experiments to determine
      susceptibility by using time elapsed since removal of fruit from tree as the
      experimental variable. We trapped adult Anastrepha (n = 7,936) in all orchards
      and dissected fruit (n = 7,695) from orchards and packing houses (n = 1,620) in
      search of eggs or larvae. Most (96.7%) A. ludens, A. obliqua, A. striata, and A.
      serpentina adults were captured in low-elevation orchards. No eggs or larvae were
      detected in any of the fruit from foraging behavior studies or dissected fruit
      from orchards or packing houses. Of 5,200 mature, intact fruit on trees in the
      field forcibly exposed to no-choice female oviposition activity (five
      females/fruit), we only found four fruit infested by A. ludens but no adults
      emerged. 'Hass' avocados only became marginally susceptible to attack by A.
      ludens (but not A. obliqua, A. serpentina, and A. striata) 24 h after being
      removed from the tree. Fruit placed on the ground in orchards (n = 3,600) were
      occasionally infested by Neosilba batesi (Curran) (Diptera: Lonchaeidae), a
      decomposer, but not Anastrepha spp. Based on our results, commercially cultivated
      and marketed P. americana 'Hass' should not be considered a natural host of A.
      ludens, A. obliqua, A. striata, and A. serpentina in Mexico.

PMID- 15154449
TI  - Two low-cost food attractants for capturing Toxotrypana curvicauda (Diptera:
      Tephritidae) in the field.
AB  - Adults of the papaya fruit fly, Toxotrypana curvicauda Gerstaecker, living in
      wild vegetation in Yautepec, Morelos, Mexico, were captured using McPhail traps
      baited with pineapple juice or brown sugar. Maximum capture peaks occurred during
      August and November in the afternoon. Baits were most effective when aged over a
      4-d period. Traps baited with brown sugar captured the highest number of adults,
      and both baits were more attractive to females than males. Potential use of these
      baits for pest management and research is discussed, considering that this is the
      first report of pineapple juice being attractive to the papaya fruit fly.

PMID- 15154450
TI  - Rates of population increase, abundance, and life stage distribution of
      Rhynchites cribripennis (Coleoptera: Attelabidae) on trees and in the soil in an
      olive grove.
AB  - The seasonal population abundance of Rhynchites cribripennis (Desbrochers) adults
      on olive trees was studied by collecting samples from an olive grove on the
      island of Zakynthos, Greece, from April 1994 to the end of July 1995. Moreover,
      the population abundance of larvae, pupae, and adults of R. cribripennis was
      recorded in soil samples from two soil depths (0-4 and 4-8 cm) from October 1994
      to October 1995. Results showed that adult populations increased considerably on
      trees during May and June and peaked on 16 June (19.9 adults per twig) and 8 July
      (7.7 adults per twig) in 1994 and 1995, respectively. In 1994, no significant
      differences were found in the number of adults sampled from the different tree
      quadrants (northwest [NW], northeast [NE], southwest [SW], and southeast [SE]).
      However, in 1995, adult numbers in the NW quadrant of trees were significantly
      higher than those in the SE or SW quadrants. In soil samples, larvae were
      recorded throughout the sampling period with the highest numbers occurring in
      December, 2.4 larvae per soil sample, whereas pupae were found in lowest numbers
      in October and November. Adults were present in the soil samples from December to
      May, but the highest numbers were recorded in December, with a peak of one adult
      per sample. The number of adults was significantly higher, and that of larvae
      numerically higher, in the upper compared with lower soil layer, whereas pupae
      were found with similar numbers in both soil layers. Results of these studies
      suggest that this weevil exhibits a prolonged larval diapause and a 2-yr life
      cycle. The ecological implications of this behavior are discussed. Moreover, a
      prediction of the highest adult population on trees was estimated by taking into
      account the rate of increase of adult numbers in the early period of adult
      occurrence on trees.

PMID- 15154451
TI  - Effect of trap type, trap color, trapping location, and pheromone dispenser on
      captures of male Palpita unionalis (Lepidoptera: Pyralidae).
AB  - Field studies were conducted to evaluate the influence of trap design, trapping
      location, type of pheromone dispenser, and trap color on the capture of Palpita
      unionalis (Hubner) males, in olive groves. The experiments were carried out in
      two regions, Alexandria (northern Greece) and Oropos (central Greece), where
      olives are cultivated. In both regions, the majority of the males (> 70% of the
      total) were caught from late autumn to early winter, whereas < 1% was caught
      during July and August. Among the trap types used, the Funnel was significantly
      more attractive than Delta, Pherocon 1C, and Pherocon II traps. More males were
      caught in traps placed at the periphery of the groves than those placed in the
      center. Among the four colored traps tested, white traps were the most effective.
      However, a significant difference in trap catches was found between white and
      brown traps. Traps baited with red rubber septa captured more males than those
      baited with the white one. The use of these parameters in monitoring and managing
      P. unionalis is discussed.

PMID- 15154452
TI  - Disruption of host location of western corn rootworm larvae (Coleoptera:
      Chrysomelidae) with carbon dioxide.
AB  - Elevated concentrations of carbon dioxide (CO2) prevented neonate larvae of the
      western corn rootworm, Diabrotica virgifera virgifera LeConte, from locating the
      roots of growing corn in behavioral bioassays conducted in soil tubs. When CO2
      was pumped into one end of a soil tub, significantly more larvae were recovered
      from soil at the treated end than from soil around a growing corn plant at the
      opposite end of the tub. In controls with ambient air pumped into one end of a
      soil tub, significantly more larvae were recovered from the soil around the corn
      plant than from soil on the treated side. Larvae were unable to locate the roots
      of corn seedlings when CO2-generating materials were mixed into the soil. CO2
      concentrations in soil were measured by mass spectrometry with selected ion
      monitoring at m/z 44. Granules composed of baker's yeast, yeast nutrients, and an
      organic substrate were prepared as a CO2 source and were tested in larger soil
      tub bioassays. Significantly fewer larvae were recovered from corn roots in the
      soil tubs with yeast granules than from corn roots in control soil tubs. The CO2
      generating granules produced soil CO2 concentrations between 15.8 and 18.5
      mmol/mol (compared with 1.7-2.6 mmol/mol in control tubs), and this was
      sufficient to prevent larvae from locating corn roots. In field trials, organic
      and inorganic CO2- generating treatments resulted in root ratings that were
      significantly lower than for the control plants.

PMID- 15154453
TI  - Biological control of Lobesia botrana (Lepidoptera: Tortricidae) larvae by using
      different formulations of Bacillus thuringiensis in 11 vine cultivars under field
      conditions.
AB  - This work describes the results of an experiment that was conducted in the
      vineyard of the American Farm School, Thermi, Thessaloniki Greece, during 2001.
      Its aim was to study the efficacy of two formulations of Bacillus thuringiensis
      Berliner (wettable powder and dust) to control the larvae of Lobesia botrana
      Denis & Schiffermueler (Lepidoptera: Tortricidae). The experimental results
      showed that the two formulations of B. thuringiensis are significantly more
      effective than the control, the dusting being more effective in most cultivars
      (Asyrtico, Sauvignon blanc, Debina, Athiri, Agiorgitico, Limnio, Syrah, and
      Cabernet sauvignon), and the spraying in a few cultivars (Xinomavro, Roditis, and
      Chardonnay). Dusting in the blue-black cultivars was found to be more effective
      than spraying, this not being the case in the yellow-green cultivars. This fact
      should be taken into consideration when cultivars of different color were planted
      in the same field. Single dusting proved to be better in cultivars with loose,
      average and dense berry cluster compactness, whereas double spraying gave better
      results in compact cultivars.

PMID- 15154454
TI  - Discrimination by male dogwood borer, Synanthedon scitula (Lepidoptera:
      Sesiidae), among traps baited with commercially available pheromone lures.
AB  - The response of male dogwood borer, Synanthedon scitula (Harris) (Lepidoptera:
      Sesiidae), to four commercially available pheromone lures and to pheromone source
      concentration was evaluated in field trapping studies in commercial apple
      orchards in Virginia and West Virginia Male peachtree borer, Synanthedon exitiosa
      (Say), lesser peachtree borer, Synanthedon pictipes (Grote & Robinson), and lilac
      borer, Podosesia syringae (Harris), were also captured in traps baited with all
      lures tested. Among the lures used, the Scenturion dogwood borer lure was the
      most attractive to and selective for dogwood borer. Male dogwood borer showed a
      concentration-dependent response to traps baited with different source
      concentrations of the pheromone from Scenturion. Chemical analyses revealed that
      all lures contained principally (Z,Z)-3,13-octadecadien-1-ol acetate (ODDA) but
      that a significantly higher percentage of (Z,E) plus (E,Z)-3,13-ODDA was present
      in the Scenturion lure, compared with the others. Weekly collections of fresh
      male and female dogwood borer pupal exuviae from April until October in 2002 and
      2003 suggested that traps baited with Scenturion lures significantly
      underestimated the size of populations in commercial apple orchards.

PMID- 15154455
TI  - Floral characteristics affect susceptibility of hybrid tea roses, Rosa x hybrida,
      to Japanese beetles (Coleoptera: Scarabaeidae).
AB  - The Japanese beetle, Popillia japonica Newman, feeds on the flowers and foliage
      of roses. Rosa x hybrida. Beetles attracted to roses land almost exclusively on
      the flowers. This study evaluated characteristics of rose flowers including
      color, size, petal count and fragrance, as well as height of plants and blooms
      within plant as factors in attractiveness to Japanese beetles. Artificial flowers
      that had been painted to match the spectral reflectance of real blooms were
      attached to potted nonflowering rose plants in the field and the number of
      beetles that landed on each model was recorded. More beetles landed on the yellow
      and white-colored flower models than on the five other bloom colors that were
      tested. Large (15 cm diameter) yellow flower models attracted more beetles than
      did smaller (8 cm diameter) yellow models. There was no difference in beetle
      response to yellow flower models of the same size that differed in bloom
      complexity (i.e., number of petals). Experiments in which blooming rose plants
      were elevated above controls, or in which flower models were placed at different
      heights within plant canopies, failed to support the hypothesis that height per
      se accounts for beetles' attraction to flowers over leaves. Attractiveness of
      selected rose cultivars that varied in fragrance and flower color also was
      evaluated in the field. Yellow-flowered cultivars were more susceptible than
      those with red flowers, regardless of fragrance intensity as rated by breeders.
      Growing cultivars of roses that have relatively dark and small-sized blooms may
      have some benefit in reducing Japanese beetles' attraction to roses.

PMID- 15154456
TI  - Sex pheromone of the citrus mealybug Planococcus citri: synthesis and
      optimization of trap parameters.
AB  - A simple synthesis of the pheromone of the citrus mealybug, Planococcus citri
      (Risso) (Hemiptera: Pseudococcidae), has been developed. Various factors
      affecting capture of males have been assessed to optimize the trap design and to
      develop a lure with high efficacy and longevity. Male capture was the same with
      the racemic and chiral pheromone; technical pheromone (85% purity) was
      statistically as attractive as pure pheromone (97%). A special formulation was
      used to determine the actual release rate of the pheromone under field conditions
      as related to male capture. Generally, plate traps caught more males than delta
      traps, and large traps caught more than small ones. The effects of aging on the
      performance of three types of rubber dispensers were evaluated. It was found that
      the American dispenser displayed the most consistent trapping performance and
      could be used for monitoring for at least 16 wk with a load of 200 microg of
      pheromone. The dose-response of the males to sex pheromone was tested within the
      range of 25-1,600 microg.

PMID- 15154457
TI  - Effects of clothianidin on Bombus impatiens (Hymenoptera: Apidae) colony health
      and foraging ability.
AB  - We conducted laboratory experiments to investigate the lethal and sublethal
      effects of clothianidin on bumble bee, Bombus impatiens Cresson, colony health
      and foraging ability. Bumble bee colonies were exposed to 6 ppb clothianidin,
      representing the highest residue levels found in field studies on pollen, and a
      higher dose of 36 ppb clothianidin in pollen. Clothianidin did not effect pollen
      consumption, newly emerged worker weights, amount of brood or the number of
      workers, males, and queens at either dose. The foraging ability of worker bees
      tested on an artificial array of complex flowers also did not differ among
      treatments. These results suggest that clothianidin residues found in seed
      treated canola and possibly other crops will not adversely affect the health of
      bumble bee colonies or the foraging ability of workers.

PMID- 15154459
TI  - Irradiation of Anastrepha obliqua (Diptera: Tephritidae) revisited: optimizing
      sterility induction.
AB  - The effects of irradiation doses increasing from 0 to 100 Gy (1 Gy is energy
      absorbed in J kg(-1) of irradiated material) on fertility, flight ability,
      survival, and sterile male mating performance were evaluated for mass-reared
      Anastrepha obliqua (Macquart). High sterility values (> 98.2%) for irradiated
      males were obtained for doses as low as 25 Gy. Egg hatch was inhibited for
      irradiated males crossed with irradiated females at a low dose of 20 Gy. However,
      we estimated that to achieve 99.9% sterility (standard goal of many sterile
      insect technique programs), irradiation doses had to be increased to a dose
      between 50 and 75 Gy. At doses of 25 Gy and greater, we observed a decreasing
      trend in adult flight ability and an increasing trend in adult mortality. Such
      differences were greater for pupae irradiated at a young age compared those
      irradiated 24 h before emergence. Our single most relevant finding was that
      sterility induction (i.e., oviposition of nonfertilized eggs) was two times
      greater for males irradiated at low doses (40 Gy) than for males irradiated at
      high doses (80 Gy) when used at a 3:1:1 sterilized male to fertile male to
      fertile female ratio. Males irradiated at high doses may have been outcompeted by
      unirradiated males when courting unirradiated females. Implications of our
      findings for sterile insect technique programs are discussed.

PMID- 15154458
TI  - Damage loss assessment and control of the cereal leaf beetle (Coleoptera:
      Chrysomelidae) in winter wheat.
AB  - Cereal leaf beetle, Oulema melanopus (L.), invaded northern Alabama and Georgia
      more than a decade ago and since has become an economic pest of winter wheat and
      other cereal crops in the southeastern United States. A series of trials was
      conducted beginning in 1995 to determine optimal rate and timing of applications
      of selected foliar insecticides for managing cereal leaf beetle in soft red
      winter wheat. These trials, cage studies with larvae, and a manual defoliation
      experiment were used to provide information on cereal leafbeetle yield loss
      relationships and to develop economic decision rules for cereal leaf beetle in
      soft red winter wheat. Malathion, methomyl, carbaryl, and spinosad effectively
      controlled larval infestations when treatments were applied after most eggs had
      hatched. Encapsulated endotoxin of Bacillus thuringiensis, methyl parathion, and
      disulfoton applied at the lowest labeled rates were not effective treatments.
      Organophosphate insecticides generally were not effective when applied before
      most eggs had hatched. The most effective treatments were the low rates of lambda
      cyhalothrin when applied early while adults were still laying eggs and before or
      near 50% egg hatch. These early applications applied at or before spike emergence
      virtually eliminated cereal leaf beetle injury. The manual defoliation study
      demonstrated that defoliation before spike emergence has greater impact on grain
      yield and yield components than defoliation after spike emergence. Furthermore,
      flag leaf defoliation causes more damage than injury to lower leaves. Grain test
      weight and kernel weight were not affected by larval injury in most trials.
      Regression of larval numbers and yield losses calculated a yield loss of 12.65%
      or 459 kg/ha per larva per stem, which at current application costs suggested an
      economic threshold of 0.4 larvae per stem during the spike emergence to anthesis
      stages.

PMID- 15154460
TI  - Ovarian development and ovipositional preference of the western corn rootworm
      (Coleoptera: Chrysomelidae) variant in east central Illinois.
AB  - The rotation of maize, Zea mays L., and soybean, Glycine max (L.) Merr., has been
      the traditional cultural tactic to manage the western corn rootworm, Diabrotica
      virgifera virgifera LeConte, in the Corn Belt. The reduced effectiveness of this
      rotation as a pest management tool in east central Illinois, northern Indiana,
      and southern Michigan can be explained by the shift in the ovipositional behavior
      of the new variant of western corn rootworm. The objective of this study was to
      evaluate the influence of maize, soybean, oat, Avena sativa L., stubble, and
      alfalfa, Medicago sativa L., on the ovarian development and ovipositional
      preferences of the variant western corn rootworm. Field research was conducted
      near Urbana, IL, during 1998-2000. Gravid females were present throughout the
      season in all crops, and due to the prolonged period in which western corn
      rootworm females can lay eggs, none of the crops were immune from oviposition.
      Results indicated that the western corn rootworm variant oviposits in maize,
      soybean, oat stubble, and alfalfa In 1998 and 1999, maize was the preferred
      oviposition site among crops; however, in 2000, maize, soybean, and oat stubble
      treatments had similar densities of western corn rootworm eggs. Lack of
      oviposition preference of the western corn rootworm variant demonstrated in this
      experiment represents a reasonable explanation of why the effectiveness of the
      rotation strategy to control western corn rootworm has diminished.

PMID- 15154461
TI  - Economic impact of Hessian fly (Diptera: Cecidomyiidae) on spring wheat in Oregon
      and additive yield losses with Fusarium crown rot and lesion nematode.
AB  - Damage caused by Hessian fly, Mayetiola destructor (Say), was quantified in
      spring wheat, Triticum aestivum L., trials near Pendleton and Moro, OR, during
      2001 and 2002. Five field experiments were established to examine genetic
      resistance to Fusarium crown rot, Fusarium pseudograminearum (O'Donnell & Aoki),
      and economic damage by lesion nematode, Pratylenchus neglectus (Rensch, 1924)
      (Filipjev Schuurmanns & Stekhoven, 1941) and Pratylenchus thornei (Sher & Allen,
      1941). Hessian fly became the dominant factor affecting grain yield in four
      experiments. Genotypes carrying the H3-resistance gene had grain yields 66 and
      68% higher than susceptible genotypes in cultivar trials during 2001 and 2002,
      respectively. Yield reductions were detected when Hessian fly infestation rates
      exceeded 50% plants during 2001 and 15% plants (8% tillers) during 2002. In two
      trials during 2001, in-furrow application of aldicarb (Temik) at planting
      improved yields of four Hessian fly-susceptible cultivars by 72 and 144% (up to
      1,959 kg/ha) and yields of one Hessian fly-resistant cultivar by 2 and 3%.
      Resistant cultivars and aldicarb improved grain quality as much as two market
      grades during 2001. The value of increased grain production with Hessian fly
      resistant cultivars in four field experiments ranged from dollar 112 to dollar
      252/ha, excluding price incentives for improved market quality. Yield reduction
      due to combined damage from Hessian fly and either Fusarium crown rot or lesion
      nematode was additive. This report seems to be the first quantitative yield loss
      estimate for Hessian fly in spring wheat in the semiarid environment of the
      inland Pacific Northwest.

PMID- 15154462
TI  - Effects of burial and soil condition on postharvest mortality of boll Weevils
      (Coleoptera: Curculionidae) in fallen cotton fruit.
AB  - Effects of soil condition and burial on boll weevil, Anthonomus grandis grandis
      Boheman, mortality in fallen cotton, Gossypium hirsutum L., fruit were assessed
      in this study. During hot weather immediately after summer harvest operations in
      the Lower Rio Grande Valley of Texas, burial of infested fruit in conventionally
      tilled field plots permitted significantly greater survival of weevils than in no
      tillage plots. Burial of infested squares protected developing weevils from heat
      and desiccation that cause high mortality on the soil surface during and after
      harvest in midsummer and late summer. A laboratory assay showed that burial of
      infested squares resulted in significantly greater weevil mortality in wet than
      in dry sandy or clay soils. Significantly fewer weevils rose to the soil surface
      after burial of infested bolls during winter compared with bolls set on the soil
      surface, a likely result of wetting by winter rainfall. A combination of leaving
      infested fruit exposed to heat before the onset of cooler winter temperatures and
      burial by tillage when temperatures begin to cool might be an important tactic
      for reducing populations of boll weevils that overwinter in cotton fields.

PMID- 15154463
TI  - Deterrent effects of four neem-based formulations on gravid female boll weevil
      (Coleoptera: Curculionidae) feeding and oviposition on cotton squares.
AB  - Three commercial neem-based insecticides, Agroneem, Ecozin, and Neemix, and a
      neem seed extract formulation, bitters, containing 1,036, 16,506, 471, and 223
      microg/ml azadirachtin, respectively, were assessed for feeding and oviposition
      deterrence against gravid female boll weevils, Anthonomus grandis grandis
      Boheman, in the laboratory. In choice assays, excised cotton squares dipped in
      the separate formulations were first physically contacted by the weevils' tarsi
      or antennae fewer times than nontreated control squares. In choice and no-choice
      assays, each formulation repelled the weevils for > or = 90 min. After 24 h in
      the choice assays, feeding punctures on the squares treated with Agroneem,
      Ecozin, or bitters were significantly fewer compared with controls. Egg punctures
      on the Ecozin- and the bitters-treated squares were significantly fewer than on
      control squares after 24 h. In the no-choice assay, no significant difference was
      detected. Aging the formulations under outdoor conditions for 24 h before weevils
      were exposed resulted in 46-60% and 62-82% reductions in feeding and oviposition
      punctures, respectively, compared with controls. Agroneem- and bitters-treated
      squares had > 37% fewer feeding punctures after being aged for 48 h. No
      significant difference was detected after 72 h of aging. Because the deterrence
      of the gravid female boll weevils was not correlated with amounts of
      azadirachtin, azadirachtin does not seem to be the only, or the most influential,
      component of neem that induced the observed deterrence.

PMID- 15154464
TI  - Ultralow rates of spinosad in phagostimulant granules provide control of
      Spodoptera frugiperda (Lepidoptera: Noctuidae) in maize.
AB  - Field trails in 2002 and 2003 were performed to determine the efficacy of maize
      flour-based granular formulations with ultralow rates of the naturally derived
      insecticide spinosad (0.1, 0.3, and 1.0 g [AI]/ha), for control of Spodoptera
      frugiperda (J.E. Smith) in maize, Zea mays L., in southern Mexico. Spinosad
      formulations were compared with a chemical standard, a commercial granular
      formulation of chlorpyrifos (150 g [AI]/ha). In both years, application of
      spinosad resulted in excellent levels of control, indicated by the number of
      living S. frugiperda larvae recovered from experimental plots. The efficacy of
      spinosad applied at 0.3 and 1.0 g (AI)/ha was very similar to that of
      chlorpyrifos. Natural reinfestation caused S. frugiperda numbers in insecticide
      treated plots to return to values similar to the control treatmentby 10-15d
      postapplication. Many spinosad-intoxicated larvae collected in the field died
      later in the laboratory in 2002, but not in 2003. Percentage mortality due to
      parasitoid emergence did not differ in any treatment in either field trial. The
      number of parasitoids that emerged from S. frugiperda collected in each treatment
      was significantly reduced after application of spinosad (all rates) or
      chlorpyrifos due to a reduction in the number of host larvae. Parasitoid numbers
      returned to control values by 9-15 d postapplication in all treatments. The most
      prevalent parasitoid was the braconid Chelonus insularis Cresson, which
      represented approximately 80% of emerging parasitoids in both years. We conclude
      that appropriate formulation technology can greatly enhance the performance of
      this naturally derived, biorational insecticide.

PMID- 15154465
TI  - Assessing the use of butterflies as indicators of logging in Borneo at three
      taxonomic levels.
AB  - Logging is an issue of major conservation concern. Less than 5% of tropical
      forests are currently protected, and many of these are in so-called "paper
      parks." Many species may therefore depend on exploited forests, and management
      decisions concerning these forests will be a major determinant of their survival.
      An important aspect of forest management will entail the use of reliable,
      practical, and inexpensive indicator taxa to monitor exploitation. Here,
      butterflies are proposed as such indicators. Species, generic, and subfamily
      richness was significantly higher in logged than unlogged forest and community
      composition differed significantly at all three taxonomic levels (species, genus,
      and subfamily). Richness estimators were, furthermore, highly correlated among
      all three taxonomic levels. Significant individual indicator taxa were found at
      all three taxonomic levels, but the best overall taxa (highest indicator values)
      were found at the generic level and included the butterfly genera Ragadia and
      Paralaxita as indicators of unlogged forest and the genera Ypthima, Allotinus,
      and Athyma as indicators of logged forest. The use of genera instead of species
      presents a number of practical advantages. Identification is faster, easier, and
      more reliable. Genera can, furthermore, usually be identified "on the wing,"
      thereby preventing accidental mortality due to capture.

PMID- 15154466
TI  - Importance of log size on host selection and reproductive success of Ips pini
      (Coleoptera: Scolytidae) in ponderosa pine slash of northern Arizona and western
      Montana.
AB  - Pine engraver, Ips pini (Say), often use thinning slash, and their populations
      are known to be influenced by the condition of this material. In our study, we
      evaluated the importance of three log diameters (5, 10, and 20 cm) and three
      lengths (60,120, and 240 cm) on various parameters of bark beetle host attack,
      development, and emergence. Evaluation of slash colonization in northern Arizona
      (near Flagstaff) and western Montana (near Missoula) over several years, during
      both spring and summer reproductive periods, indicated that the size of material
      selected by pine engraver differed by state, year, and season. However, within
      individual trials and over all trials, a trend in preference for larger diameter
      logs was apparent, whereas log length was of little effect. When evaluating only
      attacked logs, results indicated that the apparent preference for larger logs was
      not followed by significantly greater reproductive performance in the larger log
      sizes. Log origin was tested as a potential factor for the difference in attack
      densities between Arizona and Montana trials. Although male beetles in Montana
      and female beetles in Arizona seemed to distinguish between local-source and
      foreign-source logs during the attack phase, the gallery development and
      reproductive success of egg, larval, and new adult stages were not significantly
      different. Ultimately, differences among the trials both in host size selection
      and in reproductive success within attacked logs were closely tied to the overall
      population density of adult beetles. The implications of these findings for
      resource managers are discussed.

PMID- 15154467
TI  - A survey of hymenopteran parasitoids of forest macrolepidoptera in the central
      Appalachians.
AB  - In 1995 and 1996, we conducted a study of the hymenopteran parasitoids of
      macrolepidopteran larvae in the George Washington National Forest (GWNF), Augusta
      County, Virginia, and the Monongahela National Forest (MNF), Pocahontas County,
      West Virginia. Macrolepidopteran larvae were collected from canopy foliage and
      from under canvas bands placed around tree boles. A total of 115
      macrolepidopteran species and 5,235 individual larvae were reared. Forty-two
      percent (2,221) of the larvae were gypsy moth, Lymantria dispar (L.)
      (Lymantriidae). A total of 43 primary and secondary (hyperparasitoid)
      hymenopteran parasitoid species were reared from 46 macrolepidopteran species.
      Hymenopteran families represented included Ichneumonidae (23 species), Braconidae
      (19), Eulophidae (6), Perilampidae (1), and Trigonalidae (1). We reared 41 and 28
      parasitoid species from the GWNF and the MNF, respectively, with 19 species
      reared from both forests. Many parasitoid species were collected infrequently,
      suggesting that they are relatively rare on the sampled hosts. The introduced
      species Cotesia melanoscela (Ratzeburg) (Braconidae), and Euplectrus bicolor
      (Swederus) (Eulophidae) were among the most commonly reared parasitoids, the
      latter reared from native hosts. The four most commonly reared native parasitoids
      were Meteorus hyphantriae, Riley (Braconidae), Microplitis near hyphantriae
      (Ashmead) (Braconidae), Aleiodes preclarus Marsh & Shaw, and Euplectrus
      maculiventris (Westwood) (Eulophidae). A total of 53 new hymenopteran parasitoid
      macrolepidopteran host records were documented. Results from this study will be
      used to evaluate long-term treatment effects of regional applications of Bacillus
      thuringiensis kurstaki, and the gypsy moth fungus Entomophaga maimaiga Humber,
      Shimazu & Soper on hymenopteran parasitoids of macrolepidopteran larvae.

PMID- 15154469
TI  - Interactions of Hylastes species (Coleoptera: Scolytidae) with Leptographium
      species associated with loblolly pine decline.
AB  - Hylastes spp. (Coleoptera: Scolytidae) were evaluated as potential vectors of
      Leptographium spp. fungi. Bark beetles were trapped from stands ofloblolly pine,
      Pinus taeda L., exhibiting a range of decline symptoms in central Alabama. Under
      controlled conditions, field-collected adult Hylastes salebrosus Eichoff
      (Coleoptera: Scolytidae) and Hylastes tenuis Eichoff (Coleoptera: Scolytidae),
      which had been surface-sterilized and inoculated with Leptographium terebrantis
      Barras & Perry and Leptographium serpens (Goid.) Wingfield, transmitted the fungi
      into 100% of wounded and unwounded loblolly root sections with which they were
      confined. None of the sterilized and uninoculated beetles transmitted any
      Leptographium spp. to roots. Significantly more H. salebrosus and H. tenuis brood
      emerged from roots infected with Leptographium species than from sterile roots,
      indicating an enhancement of Hylastes reproduction.

PMID- 15154468
TI  - Suitability of some southern and western pines as hosts for the pine shoot
      beetle, Tomicus piniperda (Coleoptera: Scolytidae).
AB  - The pine shoot beetle, Tomicus piniperda (L.), is an exotic pest that has become
      established in North America. Discovered in Ohio in 1992, it has since been found
      in at least 13 states and parts of Canada. The beetle can cause significant
      growth loss in pines, and it represents a potential threat to trees in areas
      where it has not yet become established. To evaluate this threat to native pines,
      field and laboratory tests were conducted on several common and important
      southern and western species to determine whether they are acceptable hosts for
      T. piniperda. Comparisons with Pinus sylvestris L., Scots pine, a preferred
      natural host for the beetle, were made where possible. Measurements of beetle
      attack success on southern pine billets showed that Pinus taeda L., Pinus
      echinata Miller, Pinus elliottii var. elliottii Engelmann, Pinus palustris
      Miller, and Pinus virginiana Miller (loblolly, shortleaf, slash, longleaf, and
      Virginia pine, respectively) and two western pines, Pinus ponderosa Lawson and
      Pinus contorta Douglas (ponderosa and lodgepole pine, respectively), were
      acceptable for breeding material, but brood production was highly variable. Among
      the southern pines, P. taeda and P. echinata were susceptible to shoot feeding by
      T. piniperda, whereas P. elliottii was highly resistant and P. palustris seemed
      to be virtually immune. Shoot feeding tests on the western pines were conducted
      only in the laboratory, but there was moderate-to-good survival of adults feeding
      on both species. It seems that if T. piniperda is introduced into the south and
      west it will likely establish and may cause some damage to native pines. P. taeda
      may be affected more than other southern pines because it is the most abundant
      species, it is readily attacked for brood production, which can result in
      moderately large broods, and the beetle survives well during maturation feeding
      on P. taeda shoots.

PMID- 15154470
TI  - Behavior and pollination efficiency of Nannotrigona perilampoides (Hymenoptera:
      Meliponini) on greenhouse tomatoes (Lycopersicon esculentum) in subtropical
      Mexico.
AB  - The acclimation, foraging behavior, and pollination efficiency of stingless bees
      of the species Nannotrigona perilampoides Cresson were evaluated in tomato
      (Lycopersicon esculentum Mill.) plants cultivated in two greenhouses. The
      greenhouses were divided into three areas of 16 m2, and one of the following
      treatments was used for pollination: stingless bees (SB), mechanical vibration
      (MV), and no pollination (NP). Observations were conducted once a week from 0800
      to 1600 hours during 2 mo. The acclimation of the bees to the greenhouses was
      estimated by the number of bees that did not return to the hive (lost bees) and
      by comparing the population of the colonies (brood and adults). The foraging
      activity of the bees across the day was evaluated by comparing the number of
      foragers per hour. The influence of environmental variables on the foraging
      activity was also analyzed. The pollination efficiency was compared among
      treatments through the percentage of fruit set, weight of individual fruit,
      kilograms of fruit produced per square meter, and the number of seed per fruit.
      The bees started foraging on the flowers approximately 7 d after the colonies
      were introduced to the greenhouse. There was a decline in the population of the
      colonies across the experiment, but colonies did not die out. Correlations of
      environmental variables with the foraging activity of the bees showed that none
      of them had a significant influence on pollen foraging. However, water collection
      was positively correlated with the temperature and negatively correlated with the
      humidity inside the greenhouse. The estimation of the pollination efficiency per
      treatment showed that there were significant differences in fruit set in SB (83
      +/- 4.2) and MV (78.5 +/- 6.4) compared with NP (52.6 +/- 7.6). However, the
      average weight of the fruit was similar for the three treatments (65 g). There
      were significant differences for seed number in SB (200 +/- 15.3) and MV (232 +/-
      21.4) compared with NP (120 +/- 16.6). The productivity in kilograms of fruit per
      square meter was higher in SB (5.72 +/- 0.61) and MV (5.66 +/- 0.58 kg) compared
      with NP (3.34 +/- 0.72). The number of seed was positively correlated with the
      weight of the fruit. We conclude that the use of Nannotrigona testaceicornis
      Rondani, for pollinating greenhouse tomatoes in tropical climates, could be an
      alternative to the use of highly defensive African-derived Apis mellifera or non
      native bumble bees (Bombus spp.). However, more research is needed to evaluate
      the cost/benefit on large-scale greenhouse pollination using N. perilampoides
      Cresson against other bee species and pollination methods.

PMID- 15154471
TI  - Comparison of a sprayable pheromone formulation and two hand-applied pheromone
      dispensers foruse in the integrated control of oriental fruit moth (Lepidoptera:
      Tortricidae).
AB  - The efficacy of integrated programs using a sprayable pheromone formulation or
      one of two hand-applied pheromone dispensers, and a conventional oriental fruit
      moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae) control program, was
      compared using 4-5-ha blocks of peach orchard at three Niagara Peninsula farms
      during 2000-2002. In the integrated programs, chlorpyrifos and mating disruption
      with 3M Sprayable Pheromone, Isomate OFM Rosso, or Rak 5 hand-applied dispensers
      were used to control first-generation larvae, and mating disruption alone was
      used to control second- and third-generation larvae. In the conventional program,
      chlorpyrifos was used to control first-generation larvae, and pyrethroid
      insecticides were used to control larvae of the later generations. All programs
      were effective at maintaining fruit infestation by G. molesta below the industry
      tolerance level of 1%. An integrated program using sprayable pheromone required
      the use of more supplementary insecticide applications to control second- and
      third-generation larvae than a program using hand-applied dispensers. The
      elimination of insecticide sprays from integrated program blocks did not result
      in an increase in damage by plant bugs, Lygus spp. (Hemiptera: Miridae) or by the
      plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae).

PMID- 15154472
TI  - Potato aphid, Macrosiphum euphorbiae (Thomas), in tomatoes: plant canopy
      distribution and binomial sampling on processing tomatoes in California.
AB  - A binomial sampling method for the potato aphid, Macrosiphum euphorbiae (Thomas),
      on processing tomato plants, Lycopersicon esculentum (Mill), is proposed.
      Relationships between mean number of M. euphorbiae per leaf and proportion of
      leaves infested [P(I)] with M. euphorbiae for both upper and interior leaves of
      the processing tomato varieties 'Alta' and 'Halley' are presented. A split-plot
      design was used with variety, position in the plant canopy, and block as the
      factors examined through linear regression and analysis of variance (ANOVA).
      Results supported the hypotheses that M. euphorbiae densities on upper canopy
      leaves are predictive of densities on inner canopy leaves and that proportion of
      M. euphorbiae infested leaves are predictive of mean densities per leaf. Mean M.
      euphorbiae density was greater on 'Alta' than 'Halley' tomato plants, supporting
      the assumption that 'Alta' is the more susceptible variety. Taylor's Power Law
      coefficients, a and b, were similar for proportion of M. euphorbiae-infested
      upper and inner leaves of both 'Alta' and 'Halley'. Taylor's b coefficients
      ranged from 1.57 to 1.74, indicating a highly clumped distribution for M.
      euphorbiae.

PMID- 15154473
TI  - Contact and leaf residue activity of insecticides against the sweet Corn pest
      Euxesta stigmatias (Diptera: Otitidae).
AB  - Damage by Euxesta stigmatias Loew larvae to sweet corn renders the ears
      unmarketable. This report evaluates the efficacy of insecticides labeled for
      armyworm control in Florida sweet corn against E. stigmatias adults. Tests were
      performed in controlled settings by using direct contact and dried plant residues
      of esfenvalerate, cyfluthrin, lambda-cyhalothrin, chlorpyrifos, methyl parathion,
      methomyl, and thiodicarb. Direct application of all insecticides except
      thiodicarb quickly killed or caused incapacitating sublethal affects
      (uncoordinated movement, uncontrolled twitching, and hyperextension of mouthparts
      and ovipositor) to > 75% of the flies. Low rates (0.56 kg [AI]/ha) of
      chlorpyrifos and methyl parathion provided the most efficient control, killing
      100 and 93%, respectively, within 2 h of direct contact. Low rates of pyrethroids
      induced low mortality but high sublethal effects that together immobilized nearly
      100% of adults within 1 h of exposure. Mortality reached 95% within 2 h of direct
      contact in flies treated with high rates of pyrethroids. Methomyl killed as many
      as 94%, but required 24 h to reach this level after direct treatment. Residues on
      dipped leaves and field-treated plants of all tested insecticides except methyl
      parathion were less effective at killing adults compared with direct contact
      tests. Pyrethroid residues (particularly cyfluthrin) on field planted sweet corn
      induced significantly higher levels of sublethal effects (57-70%), and for a
      longer period of time, compared with materials in the other classes of chemistry.

PMID- 15154474
TI  - Fungus gnats, Bradysia spp. (Diptera: Sciaridae), and other arthropods in
      commercial bagged soilless growing media and rooted plant plugs.
AB  - Fungus gnats, Bradysia spp., in greenhouses cause economic losses to
      horticultural producers by damaging young root systems during plant propagation,
      by spreading soilborne diseases, and by reducing the marketability of the crop.
      In a greenhouse cage study, our observations suggested that bagged soilless
      growing media or rooted plant plugs from wholesale distributors may be sources
      for the introduction of fungus gnats into commercial greenhouse facilities. To
      evaluate these possibilities, carefully collected samples of bagged soilless
      growing media stored in the greenhouse, as well as bagged soilless growing media
      and rooted plant plugs delivered from midwestern wholesale distributors, were
      incubated under controlled conditions in the laboratory. Fungus gnats emerged
      from soilless media stored in the greenhouse, soilless media delivered from
      wholesale distributors, and from rooted plant plugs delivered from wholesale
      distributors. These results demonstrate that pasteurization of even bagged
      soilless media may be essential to effectively managing greenhouse populations of
      fungus gnats. However, pasteurization is not an option for responding to
      contamination of rooted plant plugs. Preliminary evidence is provided that
      application of entomopathogenic nematodes may offer potential as a method for
      managing fungus gnats in plant plugs, so long as treatment is early. Other
      arthropods found contaminating soilless media and rooted plant plugs included the
      western flower thrips, Frankliniella occidentalis (Pergande), Collembola, Acari,
      Formicidae, Staphylinidae, Psychodidae, and other Diptera.

PMID- 15154475
TI  - 3 using odor-baited trap trees as sentinels to monitor plum curculio (Coleoptera:
      Curculionidae) in apple orchards.
AB  - In commercial orchards in Massachusetts in 2003, we conducted experiments aimed
      at developing guidelines for use of perimeter-row trap trees baited with
      grandisoic acid plus benzaldehyde as sentinels in a practical approach to
      determining need and timing of insecticide applications against overwintered plum
      curculios, Conotrachelus nenuphar (Herbst). Evaluations were based on percentages
      of sampled fruit injured by plum curculio. Trap trees baited with grandisoic acid
      released at approximately 1 mg/d plus benzaldehyde released at approximately 40
      mg/d performed as well as or better than trap trees baited with greater or lesser
      amounts of these attractants in combination. The distance over which a trap tree
      baited with such odor was effective in aggregating damage to fruit extended to at
      least 31-33 m (maximum evaluated) along a perimeter row. Trap trees at corners of
      orchard blocks were as effective as perimeter-row trap trees midway between
      corner trees. Within the canopy of a trap tree, damage did not tend significantly
      to be localized in the vicinity of the odor source but tended to be rather evenly
      distributed among various sectors of the canopy. Finally, among three candidate
      thresholds evaluated as a trigger for insecticide application, a threshold of one
      freshly injured fruit proved better than thresholds of two or four freshly
      injured fruit out of 50 fruit sampled on a trap tree in assuring that orchard
      wide damage would remain below a preset economic injury level of 1%. Our findings
      lead us to suggest that after a whole-orchard application of insecticide to apple
      trees in Massachusetts orchards shortly after petal fall, subsequent applications
      of insecticide against plum curculio can be confined to peripheral-row trees and
      be driven by a provisional threshold of one freshly injured fruit out of 50 fruit
      sampled on a perimeter-row trap tree baited with the above-mentioned odor.

PMID- 15154476
TI  - Comparison of efficacy of programs using insecticide and insecticide plus mating
      disruption for controlling the obliquebanded leafroller in apple (Lepidoptera:
      Tortricidae).
AB  - The relative efficacy of an insecticide program and an insecticide plus mating
      disruption program using a sprayable pheromone formulation or a hand-applied
      pheromone dispenser was compared for control of the obliquebanded leafroller,
      Choristoneura rosaceana (Harris) at three commercial apple farms in a production
      area along the north shore of Lake Ontario, Canada, during 2000, 2001, and 2002.
      The average rate of disruption ranged from 50 to 80% in blocks of orchard treated
      with sprayable pheromone and from 84 to 98% in blocks treated with the hand
      applied dispenser. The average proportion of shoots with larval feeding injury
      ranged from 0.002 to 0.09, 0.001 to 0.09, and 0.005 to 0.13 in the insecticide,
      insecticide plus sprayable pheromone, and insecticide plus hand-applied dispenser
      treatments, respectively, during the 3-yr study. The percentage of fruit with
      damage caused by spring, summer and overwintering larvae ranged from 0.03 to
      0.06, 0.01 to 0.02, and 0.01 to 0.03 in the insecticide, insecticide plus
      sprayable pheromone, and insecticide plus hand-applied dispenser treatments,
      respectively. The addition of sex pheromone-mediated mating disruption to a
      conventional, insecticide-based program did not provide additional control of C.
      rosaceana feeding injury to shoots or fruit. The possible reasons for the failure
      of mating disruption to provide additional control are discussed.

PMID- 15154477
TI  - Toxicity of imidacloprid-treated spheres to Caribbean fruit fly, Anastrepha
      suspensa (Diptera: Tephritidae) and its parasitoid Diachasmimorpha longicaudata
      (Hymenoptera: Braconidae) in the laboratory.
AB  - No-choice cage tests were used to study the toxicity of imidacloprid-treated
      spheres to Caribbean fruit fly, Anastrepha suspensa (Loew), and its associated
      parasitoid, Diachasmimorpha longicaudata (Ashmead), in the laboratory. Three
      imidacloprid sphere treatments (2, 4, and 8% active ingredient [AI] Provado 1.6
      F) and an untreated control sphere (no toxicant) were evaluated against A.
      suspensa. Throughout the observation period (2-72 h), all concentrations of
      imidacloprid-treated spheres killed significantly more A. suspensa compared with
      control spheres. After 4 h of exposure to imidacloprid-treated spheres,
      significantly more A. suspensa were killed on spheres treated with 8% compared
      with 2% (AI). At 48 and 72 h, there were no significant differences in the mean
      number of A. suspensa killed at 2, 4, and 8% (AI), potentially indicating that a
      period of 24 h was sufficient for flies to ingest a lethal dose of the pesticide.
      Overall, significantly more A. suspensa males were killed after 72 h of exposure
      to imidacloprid-treated spheres compared with females. For D. longicaudata, only
      two imidacloprid sphere treatments, 2 and 4% (AI), and an untreated sphere
      (control) were evaluated for mortality in cage tests. There were no significant
      differences in mortality of D. longicaudata between the 2 and 4% (AI)
      imidacloprid-treated spheres. Both rates killed significantly more D.
      longicaudata compared with the control. However, after 24, 48, and 72 h of
      exposure to imidacloprid-treated spheres, significantly more D. longicaudata were
      killed in cages containing 4% compared with 2% (AI) and untreated control
      spheres. The study demonstrates the potential use of imidacloprid-treated spheres
      for control of A. suspensa in areas where it may be difficult to apply broad
      spectrum insecticides.

PMID- 15154478
TI  - Pest phenology and evaluation of traps and pheromone lures for monitoring flight
      activity of obliquebanded leafroller (Lepidoptera: Tortricidae) in Minnesota
      apple orchards.
AB  - The efficacy of two trap designs (Pherocon 1C "wing" trap versus Pherocon VI
      "delta" trap) and two pheromone blends for monitoring obliquebanded leafroller,
      Choristoneura rosaceana (Harris), was evaluated in Minnesota apple orchards
      during the 2001 and 2002 field seasons. Two distinct flight periods of C.
      rosaceana were recorded yearly in Minnesota. Overwintered C. rosaceana larvae
      resumed activity in the spring at approximately 60 degree-days (DD) base 10
      degrees C, whereas adult emergence began approximately 275 DD base 10 degrees C.
      To determine the optimal pheromone blend for monitoring C. rosaceana in
      Minnesota, traps were baited with either a three-component pheromone blend (Z11
      14:Ac, E11-14:Ac, and Z11-14:OH) produced by females in eastern North America, or
      a four-component blend (Z11-14:Ac, E11-14:Ac, Z11-14:OH, and Z11-14:Al) commonly
      produced by females in western North America. Of the four pheromone-baited traps
      evaluated, delta traps baited with the four-component western pheromone lure
      captured the highest number of C. rosaceana males, followed by wing traps baited
      with western lure. Male C. rosaceana were less attracted to traps containing the
      three-component eastern lure, and both lure types seemed to be considerably
      selective against sympatric redbanded leafroller, Argyrotaenia velutinana
      (Walker). These results suggest that the pheromonal response of the predominant
      endemic population of C. rosaceana in Minnesota is similar to the response of the
      pest in many parts of western North America. The delta trap baited with western
      pheromone lure of C. rosaceana is recommended for monitoring the pest in
      Minnesota, and the results are discussed in relation to the development of
      effective management strategies against this important pest of apple.

PMID- 15154479
TI  - Phytophagous preferences of the multicolored Asian lady beetle (Coleoptera:
      Coccinellidae) for autumn-ripening fruit.
AB  - The objective of this study was to assess the potential pest status of Harmonia
      axyridis (Pallas) on autumn-ripening fruit. In autumn, H. axyridis has been
      observed feeding on pumpkins, apples, grapes, and raspberries in Minnesota. To
      determine whether H. axyridis can inflict primary feeding damage to fruit (i.e.,
      breaking the skin of the fruit), we conducted laboratory feeding experiments with
      undamaged pumpkins, apples, grapes, and raspberries. The only fruit that H.
      axyridis was able to damage directly was raspberry. Laboratory choice tests were
      conducted to determine whether H. axyridis exhibits a preference between damaged
      and undamaged fruit, between cultivars of fruit, and between sugar water and
      water alone. For all fruits tested, H. axyridis showed a preference for damaged
      fruits over undamaged fruits. H. axyridis also exhibited a strong preference for
      sugar water over water alone. However, few differences were exhibited in
      preference between cultivars of fruit. In autumn, it seems that H. axyridis is an
      opportunist, taking advantage of previously damaged fruit, caused by other
      agents.

PMID- 15154480
TI  - Incidence and control of dogwood borer (Lepidoptera: Sesiidae) and American plum
      borer (Lepidoptera: Pyralidae) infesting burrknots on clonal apple rootstocks in
      New York.
AB  - Surveys were conducted in the major apple growing regions of New York state to
      determine the incidence of borers infesting burrknots on clonal apple rootstocks.
      Dogwood borer, Synanthedon scitula (Harris), was generally prevalent throughout
      the state, but American plum borer, Euzophera semifuneralis (Walker), was limited
      to western New York apple orchards near infested stone fruit trees. Insecticides
      evaluated in the field for efficacy against both borers were chlorpyrifos,
      endosulfan, indoxacarb plus oil, methoxyfenozide, fenpropathrin, and kaolin clay.
      Also, white latex paint was tested alone and mixed with chlorpyrifos. One
      application of chlorpyrifos applied at the petal fall developmental stage was
      equivalent to chlorpyrifos applied at petal fall and again in mid-July, and it
      provided season-long control of dogwood borer and American plum borer. One
      application of chlorpyrifos applied any time between the half-inch green
      developmental stage and petal fall, or after harvest the previous season,
      controlled both overwintered and summer brood larvae of dogwood borer. Multiple
      applications of fenpropathrin, indoxacarb plus oil, and endosulfan applied during
      the dogwood borer flight period controlled the summer brood.

PMID- 15154481
TI  - Toxicity of plant essential oils to Tetranychus urticae (Acari: Tetranychidae)
      and Phytoseiulus persimilis (Acari: Phytoseiidae).
AB  - Fifty-three plant essential oils were tested for their toxicity against eggs and
      adults of Tetranychus urticae Koch as well as adults of Phytoseiulus persimilis
      Athias-Henriot, by using a filter paper diffusion bioassay without allowing
      direct contact. Responses varied according to oil type and dose, and mite
      species. In a plastic container (4.5 by 9.5 cm) bioassay at 14 x 10(-3) microl/ml
      air, caraway seed, citronella java, lemon eucalyptus, pennyroyal, and peppermint
      oils gave > 90% mortality against adult T. urticae, whereas 82 and 81% mortality
      was observed with sage and spearmint oils, respectively. With the exception of
      sage oil, the other six essential oils were highly effective against T. urticae
      eggs at 9.3 x 10(-3) microl/ml air. Against adult P. persimilis, these six test
      oils caused > 90% mortality at 7.1 x 10(-3) microl/ml air. Particularly
      peppermint oil at 4.7 x 10(-3) microl/ml air was highly toxic. In an acrylic cage
      (30 by 30 by 40 cm ) test, lemon eucalyptus, pennyroyal, peppermint, and
      spearmint oils were highly effective against adult T. urticae at 1.4 x 10(-3)
      microl/ml air. These results indicate that the mode of delivery of these
      essential oils was largely a result of action in the vapor phase via the
      respiratory system. The essential oils described herein merit further study as
      potential fumigants for T. urticae control.

PMID- 15154482
TI  - Cost and efficacy comparison of integrated pest management strategies with
      monthly spray insecticide applications for German cockroach (Dictyoptera:
      Blattellidae) control in public housing.
AB  - The long-term costs and efficacy of two treatment methodologies for German
      cockroach, Blattella germanica (L.), control were compared in the public housing
      environment. The "traditional" treatment for German cockroaches consisted of
      monthly baseboard and crack and crevice treatment (TBCC) by using spray and dust
      formulation insecticides. The integrated pest management treatment (IPM) involved
      initial vacuuming of apartments followed by monthly or quarterly applications of
      baits and insect growth regulator (IGR) devices. Cockroach populations in the IPM
      treatment were also monitored with sticky traps. Technician time and the amount
      of product applied were used to measure cost in both treatments. Twenty-four hour
      sticky trap catch was used as an indicator of treatment efficacy. The cost of the
      IPM treatment was found to be significantly greater than the traditional
      treatment, particularly at the initiation of the test. In the first month (clean
      out), the average cost per apartment unit was dollar 14.60, whereas the average
      cost of a TBCC unit was dollar 2.75. In the second month of treatment, the
      average cost of IPM was still significantly greater than the TBCC cost. However,
      after month 4 the cost of the two treatments was no longer significantly
      different because many of the IPM apartments were moved to a quarterly treatment
      schedule. To evaluate the long-term costs of the two treatments over the entire
      year, technician time and product quantities were averaged over all units treated
      within the 12-mo test period (total 600 U per treatment). The average per unit
      cost of the IPM treatment was (dollar 4.06). The average IPM cost was
      significantly greater than that of the TBCC treatment at dollar 1.50 per unit.
      Although the TBCC was significantly less expensive than the IPM treatment, it was
      also less effective. Trap catch data indicated that the TBCC treatment had
      little, if any, effect on the cockroach populations over the course of the year.
      Cockroach populations in the TBCC treatment remained steady for the first 5 mo of
      the test and then had a threefold increase during the summer. Cockroach
      populations in the IPM treatment were significantly reduced from an average of
      24.7 cockroaches per unit before treatment to an average 3.9 cockroaches per unit
      in month 4. The suppressed cockroach populations (< 5 per unit) in the IPM
      treatment remained constant for the remaining 8 mo of the test.

PMID- 15154483
TI  - Polyethylene barrier impregnated with lambda-cyhalothrin for exclusion of
      subterranean termites (Isoptera: Rhinotermitidae) from structures.
AB  - Polyethylene film impregnated with lambda-cyhalothrin was placed over a sand plot
      and covered with a concrete slab to allow insecticide movement into the sand for
      a period of 5.5 yr. Discs of polyethylene film and sand beneath them were sampled
      annually for 5 yr and at 5.5 yr for bioassay with the Formosan and eastern
      subterranean termite. Results demonstrated that sufficient quantities of lambda
      cyhalothrin were released from the impregnated polyethylene film into adjacent
      sand to prevent termite penetration. The impregnated film has less environmental
      impact than conventional liquid termiticides because the insecticide is held in
      the polymer. Other advantages include its dual function as a construction
      moisture barrier and ease in verifying its proper installation.

PMID- 15154484
TI  - Repellency and toxicity of mint oil granules to red imported fire ants
      (Hymenoptera: Formicidae).
AB  - Repellency and toxicity of 2% mint oil granules were evaluated against worker red
      imported fire ants. Solenopsis invicta Buren, in a series of laboratory and field
      experiments. In continuous exposure experiments, LT50 values ranged from 1.2 h
      with 164.8 mg/cm2 of 2% mint oil granules to 15.3 h with 1.65 mg/cm2 of granules.
      LT50 values declined exponentially with increasing rate of mint oil granules.
      Limited exposure to 164.8 mg/cm2 mint oil granules resulted in > 50% knock down
      (KD) after 30 min; however, there was no KD at 15 min. Twenty-four hour mortality
      increased linearly with increasing exposure time. Mean repellency of worker red
      imported fire ants ranged from 49.2 +/- 5.4% for 0 mg/cm2 (untreated control) of
      mint oil granules at 30 min to 100% for 147.8 mg/cm2 of mint oil granules at 3 h.
      Repellency increased with increasing milligrams per square centimeter of mint oil
      granules and exposure time. In field tests, 100% of mounds opened and treated
      with mint oil granules were abandoned 5 d after treatment and ants had relocated
      or formed satellite mounds by 2 d after treatment. Unopened mounds treated
      topically with mint oil granules were not abandoned, but ants formed satellite
      mounds 2 d after treatment. Mint oil granules could provide another tool for red
      imported fire ant integrated pest management, particularly in situations in which
      conventional insecticides would be inappropriate.

PMID- 15154485
TI  - Laboratory evaluation of boric acid-sugar solutions as baits for management of
      German cockroach infestations.
AB  - Boric acid dust has a long history as an insecticide in urban pest management,
      and it has been shown to be an effective alternative to conventional neurotoxic
      insecticides. However, dust formulations require specialized equipment and are
      difficult to apply, whereas gel and paste formulations contain large amounts of
      boric acid and tend to be less efficacious than other insecticide baits. The
      purpose of this study was to evaluate the effectiveness of borate solutions as
      baits against the German cockroach. Several borate-sugar combinations were
      evaluated in choice and no-choice assays in the laboratory. Mortality was
      recorded for 15 d and expressed as lethal time90, the time taken to kill 90% of
      the cockroaches. Results showed that boric acid was more effective than sodium
      tetraborate or disodium octaborate tetrahydrate and that aqueous solutions
      containing mixtures of 0.5-2% boric acid and any of several inexpensive sugars,
      including fructose, glucose, maltose, and sucrose as a phagostimulant, at molar
      concentrations of 0.05-1.0, can provide rapid and effective kill of German
      cockroaches, Blattella germanica (L.).

PMID- 15154486
TI  - Field trial of diatomaceous earth in cotton gin trash against the larger black
      flour beetle, Cynaeus angustus (Coleoptera: Tenebrionidae).
AB  - The larger black flour beetle, Cynaeus angustus (LeConte) (Coleoptera:
      Tenebrionidae), is an agricultural and home nuisance pest in North America. In
      the Southern High Plains of Texas, the larger black flour beetle is associated
      with cotton gin trash, by-products of cotton ginning that are field stored in
      large piles for economic reasons. Larger black flour beetle overwinter in gin
      trash piles but may disperse by the millions in summer and autumn, entering
      houses as far as 2 km away where they cause distress to homeowners. Because > 1.2
      billion kg of gin trash is produced annually in Texas alone, the potential
      consequences of the larger black flour beetle are enormous. We conducted a field
      experiment that evaluated the efficacy of diatomaceous earth (DE) on the
      abundance of the larger black flour beetle in gin trash. There were no
      significant differences in numbers of larger black flour beetle among treatments
      and controls (mean number of adults summed over time: controls = 115.41, layered
      treatment = 87.60, top and bottom treatment = 96.50, bottom treatment = 115.16).
      There were sufficient numbers of beetles in treated piles to still pose a
      potential home nuisance problem, likely because the moisture content of field
      stored gin trash is too high for DE to work effectively. Therefore, treating
      cotton gin trash with diatomaceous earth will probably be unable to prevent home
      infestations of larger black flour beetle. Location within a gin trash pile and
      season influenced pest numbers, which has implications for long-term field
      storage of cotton gin trash.

PMID- 15154487
TI  - Laboratory performance and pharmacokinetics of the benzoylphenylurea noviflumuron
      in eastern subterranean termites (Isoptera: Rhinotermitidae).
AB  - A benzoylphenylurea insect growth regulator with the common name noviflumuron was
      evaluated for use as a baiting toxicant against the eastern subterranean termite,
      Reticulitermes flavipes (Kollar). Noviflumuron demonstrated significantly greater
      potency and faster speed of action compared with the commercial standard
      hexaflumuron. In addition, noviflumuron was not a feeding deterrent on filter
      paper at concentrations of up to 10,000 ppm. The rates of uptake, clearance, and
      insect-to-insect transfer of [14C] noviflumuron were measured in R. flavipes in
      laboratory assays and compared with those previously reported for
      [14C]hexaflumuron. Under a continuous exposure regime, the uptake profile for
      noviflumuron was similar to that for hexaflumuron, although the time period of
      maximal uptake was shorter for noviflumuron. Noviflumuron was cleared from
      termites in a first order process with a half-life of approximately 29 d, whereas
      the half-life of hexaflumuron was much shorter (8-9 d). Noviflumuron was
      efficiently transferred from treated to untreated termites by trophallaxis via
      kinetics similar to those reported for hexaflumuron; however, the systemic dose
      of noviflumuron required to result in toxicity of R. flavipes was found to be at
      least two- to three-fold less than that of hexaflumuron. The faster activity of
      noviflumuron compared with hexaflumuron in R. flavipes can be at least partially
      explained by the combination of slower clearance and greater intrinsic activity.

PMID- 15154488
TI  - Impacts of residual insecticide barriers on perimeter-invading ants, with
      particular reference to the odorous house ant, Tapinoma sessile.
AB  - Three liquid insecticide formulations were evaluated as barrier treatments
      against perimeter-invading ants at a multifamily housing complex in West
      Lafayette, IN. Several ant species were present at the study site, including (in
      order of abundance) pavement ant, Tetramorium caespitum (L.); honey ant,
      Prenolepis imparis (Say); odorous house ant, Tapinoma sessile (Say); thief ant,
      Solenopsis molesta (Say); acrobat ant, Crematogaster ashmeadi (Mayr); crazy ant,
      Paratrechina longicornis (Latrielle), field ants, Formica spp.; and carpenter ant
      Camponotus pennsylvanicus (DeGeer). Studies began in May 2001 and concluded 8 wk
      later in July. Individual replicate treatments were placed 0.61 in (2 feet) up
      and 0.92 m (3 feet) out from the ends of 46.1 by 10.1-m (151 by 33-foot)
      apartment buildings. Ant sampling was performed with 10 placements of moist cat
      food for 1 h within treatment zones, followed by capture and removal of recruited
      ants for later counting. All treatments led to substantial reductions in ant
      numbers relative to untreated controls. The most effective treatment was
      fipronil, where 2% of before-treatment ant numbers were present at 8 wk after
      treatment. Both imidacloprid and cyfluthrin barrier treatments had efficacy
      comparative with fipronil, but to 4 and 2 wk, respectively. Odorous house ants
      were not sampled before treatment. Comparisons of ant species composition between
      treatments and controls revealed an increase in odorous house ant frequencies at
      1-8 wk after treatment in treated locations only. These results demonstrate
      efficacy for both nonrepellent and repellent liquid insecticides as perimeter
      treatments for pest ants. In addition, our findings with odorous house ant
      highlight an apparent invasive-like characteristic of this species that may
      contribute to its dramatic increase in structural infestation rates in many areas
      of the United States.

PMID- 15154490
TI  - Bioassay determination of the distribution of imidacloprid in potato plants:
      implications to resistance development.
AB  - Soil-applied imidacloprid exhibits exceptional efficacy as a systemic insecticide
      against the Colorado potato beetle, Leptinotarsa decemlineata (Say). An uneven
      distribution of the chemical within potato plants could result in differential
      concentrations, which may allow for discrimination between genotypes of varying
      susceptibility. In this study, susceptible and tolerant larvae were fed leaves
      from the lower, middle, and upper canopy of treated and untreated plants to
      characterize within-plant distribution of imidacloprid at 4, 6, 8, 10, 12, and 14
      wk after planting. Significant differences in larval mortality and development
      indicated that the concentration of imidacloprid was unevenly distributed in the
      potato foliage during 6-14 wk after planting. The concentration of imidacloprid
      was lowest in the younger tissues of the upper leaves and highest in the older,
      lower leaves. At 6 wk, a time when the postdiapause beetles are colonizing potato
      fields, the lower concentration in upper leaves was toxic to susceptible larvae
      but did not kill a substantial portion of the tolerant larvae. Results suggest
      that higher concentrations of imidacloprid in the lower canopy leaves may act as
      a toxic barrier to colonizing susceptible beetles but may allow more tolerant
      individuals to reach the upper canopy with lower concentrations. Possible
      scenarios of how different concentrations of the systemic insecticide could
      influence the rate of resistance development are discussed.

PMID- 15154489
TI  - Role of esterase enzymes in monitoring for resistance of California red scale,
      Aonidiella aurantii (Homoptera: Diaspididae), to organophosphate and carbamate
      insecticides.
AB  - Eighty-seven populations of California red scale, Aonidiella aurantii (Maskell),
      from the San Joaquin Valley of California were tested for insecticide resistance
      by using chlorpyrifos, methidathion, and/or carbaryl in a standard fruit-dip
      bioassay as well as for general esterase activity by using alpha-naphthyl acetate
      as a substrate in a colorimetric test. The percentage of individuals that
      survived a discriminating concentration of methidathion, chlorpyrifos, or
      carbaryl was significantly correlated with the percentage of individuals showing
      > 0.4 nmol of esterase activity per minute per microgram of protein in the
      colorimetric test. Scale survival of the organophosphates showed a higher
      correlation with esterase activity than survival of carbaryl. These results
      suggest that the colorimetric test of esterase activity is useful as an indicator
      of the frequency of organophosphate-resistant and, to a lesser extent, carbamate
      resistant individuals in California red scale populations. The results of tests
      for activity and inhibition of acetylcholinesterase activity suggest that
      California red scale is using increased amounts of esterase enzymes, including
      acetylcholinesterase, to sequester organophosphate and carbamate insecticides,
      rather than modified acetylcholinesterase. Third instars collected from twigs,
      leaves, and fruit showed similar levels of esterase activity. The colorimetric
      test of esterase activity is a useful tool to detect organophosphate and
      carbamate resistance in San Joaquin Valley California red scale because of its
      speed of testing over a wide range of months, allowing for within-season decision
      making by citrus growers.

PMID- 15154491
TI  - Effect of pubescence tip on soybean resistance to lepidopteran insects.
AB  - DNA marker analysis has mapped a quantitative trait locus for soybean, Glycine
      max (L.) Merr., resistance to the corn earworm, Helicoverpa zea (Boddie)
      (Lepidoptera: Noctuidae), on the USDA soybean genetic linkage map near the
      classical gene Pb, which conditions pubescence tip. This study was initiated to
      determine the effect of pubescence tip on resistance to H. zea larvae and to
      examine the effect on beet armyworm, Spodoptera exigua (Hubner) (Lepidoptera:
      Noctuidae), and soybean looper, Pseudoplusia includens (Walker) (Lepidoptera:
      Noctuidae), larvae. The effect of blunt (pb) and sharp (Pb) pubescence tip was
      tested in antixenosis and antibiosis bioassays on H. zea, S. exigua, and P.
      includens larvae with near-isolines and insect-resistant and -susceptible
      genotypes differing in pubescence tip morphology. Sharp pubescence tip
      significantly reduced defoliation (antixenosis) from H. zea, S. exigua, and P.
      includens and weight gain (antibiosis) of H. zea. The weight gain of P. includens
      was unaffected, and S. exigua weight gain was significant for one pair of near
      isolines differing in pubescence tip but not the other. The results indicate that
      sharp pubescence tip would be beneficial to introgress into elite soybean
      germplasm due to its association with resistance to H. zea, S. exigua, and P.
      includens.

PMID- 15154492
TI  - Evaluation of the European Union Maize Landrace Core Collection for resistance to
      Sesamia nonagrioides (Lepidoptera: Noctuidae) and Ostrinia nubilalis
      (Lepidoptera: Crambidae).
AB  - Two corn borer species are the principal maize insect pests in Europe, the
      European corn borer, Ostrinia nubilalis (Hubner), and the pink stem borer,
      Sesamia nonagrioides (Lefebvre). Hence, it would be advisable to evaluate the
      European maize germplasm for corn borer resistance to generate European varieties
      resistant to corn borer attack. The creation of the European Union Maize Landrace
      Core Collection (EUMLCC) allowed the screening of most of the variability for
      European corn borer resistance present among European maize local populations
      from France, Germany, Greece, Italy, Portugal, and Spain, testing a
      representative sample. The objective of this study was the evaluation of stem and
      ear resistance of the EUMLCC to European corn borer and pink stem borer attack.
      Trials were made at two Spanish locations that represent two very different maize
      growing areas. Populations that performed relatively well under corn borer
      infestation for stem and ear damage were 'PRT0010008' and'GRC0010085', among very
      early landraces; 'PRT00100120' and 'PRT00100186', among early landraces;
      'GRC0010174', among midseason landraces; and 'ESP0070441', among late landraces.
      Either the selection that could have happen under high insect pressure or the
      singular origin of determined maize populations would be possible explanations
      for the higher corn borer resistance of some landraces. Landraces 'PRT0010008',
      'FRA0410090', 'PRT00100186', and 'ESP0090214' would be selected to constitute a
      composite population resistant to corn borers and adapted to short season,
      whereas populations 'ESP0090033', 'PRT00100530', 'GRC0010174', and 'ITA0370005'
      would be used to make a resistant composite adapted to longer season.

PMID- 15154493
TI  - Antibiosis and tolerance to five species of spittlebug (Homoptera: Cercopidae) in
      Brachiaria spp.: implications for breeding for resistance.
AB  - Several genera and species of spittlebugs (Homoptera: Cercopidae) are economic
      pests of Brachiaria spp. grasses in tropical America. To support current breeding
      programs aimed at obtaining multiple spittlebug resistance, we undertook a series
      of studies on antibiosis and tolerance as possible mechanisms of resistance to
      five major spittlebug species affecting Brachiaria spp. in Colombia: Aeneolamia
      varia (F.), Aeneolamia reducta (Lallemand), Zulia carbonaria (Lallemand), Zulia
      pubescens (F.), and Mahanarva trifissa (Jacobi). Four host genotypes, well known
      for their reaction to A. varia attack, were used to compare their resistance to
      other spittlebug species: CIAT 0654 and CIAT 0606 (susceptible) and CIAT 6294 and
      CIAT 36062 (resistant). CIAT 0654 and CIAT 36062 were used in antibiosis studies.
      Tolerance studies were conducted with CIAT 0654, CIAT 6294, and CIAT 36062. Sixty
      five hybrid-derived clones were used to identify levels of multiple resistance to
      three spittlebug species. The levels of antibiosis resistance in CIAT 36062
      clearly differed by spittlebug species and were classified as follows: very high
      for M. trifissa, high for A. varia and A. reducta, moderate for Z. pubescens, and
      absent for Z. carbonaria. Our results suggest the presence of true tolerance to
      Z. carbonaria in CIAT 6294 and CIAT 36062, true tolerance to Z. pubescens in CIAT
      6294 and a combination of tolerance and antibiosis as mechanisms of resistance to
      Z. pubescens in CIAT 36062. Of the 65 hybrid clones tested with A. varia, A.
      reducta, and Z. carbonaria, 15 combined resistance to two species and three
      showed antibiosis resistance to all three spittlebug species.

PMID- 15154494
TI  - Aphid (Hemiptera: Aphididae) resistance in wheat near-isogenic lines.
AB  - Plant and aphid biomass, photosynthetic pigment (chlorophylls a and b and
      carotenoids) concentrations, and chlorophyll a/b and chlorophyll/carotenoid
      ratios were quantified in aphid-infested 'Tugela' near-isogenic lines (Tugela,
      Tugela-Dn1, Tugela-Dn2, and Tugela-Dn5). The objectives were to quantify changes
      of photosynthetic pigments (chlorophylls a and b, and carotenoids) caused by
      aphid feeding and assess resistance of wheat isolines through aphid and plant
      biomass analysis. Biomass of bird cherry-oat aphid, Rhopalosiphum padi (L.)
      (Hemiptera: Aphididae)-infested plants was lower than Russian wheat aphid,
      Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae),- infested plants. When
      infested by D. noxia, all lines showed increased biomass over time, except Tugela
      where biomass decreased on day 12. No difference in plant biomass was detected
      among R. padi-infested and uninfested wheat lines. Biomass of D. noxia from
      Tugela (D. noxia-susceptible) was significantly higher than from plants with
      Diuraphis noxia-resistant Dn genes. Diuraphis noxia biomass from Tugela-Dn1 and
      Dn2 lines was not different from each other, but they were lower than from Tugela
      Dn5. In contrast, there was no difference in R. padi biomass among wheat lines.
      Concentrations of chlorophylls a and b and carotenoids were significantly lower
      in D. noxia-infested plants compared with R. padi-infested and uninfested plants.
      When infested by D. noxia, chlorophyll a and b concentrations were not different
      among wheat lines on day 3, but they were lower in Tugela and Tugela-Dn1 than in
      Tugela-Dn2 and -Dn5 plants on days 6 and 12. However, no difference was detected
      in chlorophyll a/b or chlorophyll/carotenoid ratio among Tugela lines. The study
      demonstrated that Dn genes in the Tugela isolines conferred resistance to D.
      noxia but not to R. padi. Tugela-Dn1 was antibiotic, Tugela-Dn2 was tolerant and
      antibiotic, and Tugela-Dn5 was moderately antibiotic.

PMID- 15154495
TI  - Phenotypic mechanisms of host resistance against greenbug (Homoptera: Aphididae)
      revealed by near isogenic lines of wheat.
AB  - Interactions between biotype E greenbug, Schizaphis graminum (Rondani), and
      wheat, Triticum aestivum L., were investigated using resistant and susceptible
      near isogenic lines of the greenbug resistance gene Gb3. In an antixenosis test,
      the greenbugs preferred susceptible plants to resistant ones when free choice of
      hosts was allowed. Aphid feeding resulted in quick and severe damage to
      susceptible plants, which seemed to follow a general pattern spatially and was
      affected by the position where the greenbugs were initially placed. Symptom of
      damage in resistant plants resembled senescence. Within-plant distribution of
      aphids after infestation was clearly different between the two genotypes.
      Significantly more greenbugs fed on the first (oldest) leaf than on the stem in
      resistant plants, but this preference was reversed in the susceptible one. After
      reaching its peak, aphid population on the susceptible plants dropped quickly.
      All susceptible plants were dead in 10-14 d after infestation due to greenbug
      feeding. Aphid population dynamics on resistant plants exhibited a multipeak
      curve. After the first peak, the greenbug population declined slowly. More than
      70% of resistant plants were killed 47 d after infestation. Performance of both
      biotype E and I greenbugs on several Gb3-related wheat germplasm lines were also
      examined. It seems that the preference-on-stem that was characteristic of biotype
      E greenbugs on the susceptible plants was aphid biotype- and host genotype
      dependent. Results from this study suggested that antixenosis, antibiosis, and
      tolerance in the resistant plants of wheat might all contribute to resistance
      against greenbug feeding.

PMID- 15154496
TI  - Enzymatic chlorophyll degradation in wheat near-isogenic lines elicited by cereal
      aphid (Homoptera: Aphididae) feeding.
AB  - Chlorophyll degradation enzyme (i.e., chlorophyllase, Mg-dechelatase, and
      chlorophyll oxidase) activities of aphid-infested and uninfested 'Tugela' and
      Tugela near-isogenic wheat lines (i.e., Tugela-Dn1, Tugela-Dn2, and Tugela-Dn5)
      were assayed. Chlorophyllase activity was higher in bird cherry-oat aphid,
      Rhopalosiphum padi (L.) (Homoptera: Aphididae),-infested wheat lines compared
      with Russian wheat aphid, Diuraphis noxia (Mordvilko) (Homoptera: Aphididae)]
      infested and uninfested plants. Mg-dechelatase activity was higher in D. noxia
      infested wheat lines than in R. padi-infested and uninfested plants. Also, Mg
      dechelatase activity was lower in Tugela wheat infested with D. noxia than in
      Tugela near-isogenic lines with Dn genes. Based on the in vitro assays of
      chlorophyll degradation enzyme (i.e., chlorophyllase and Mg-dechelatase)
      activities, we proposed that the chlorotic symptoms observed on D. noxia-infested
      Tugela wheat were most likely to be elicited by unbalanced chlorophyll
      biosynthesis and degradation.

PMID- 15154497
TI  - Long-term seasonal abundance patterns of Helicoverpa zea and Heliothis virescens
      (Lepidoptera: Noctuidae) in the Texas High Plains.
AB  - Bollworm, Helicoverpa zea (Boddie), and tobacco budworm, Heliothis virescens
      (F.), male adult (moth) activities were monitored between 1982 and 1995 by using
      sex pheromone traps in the Texas High Plains. Moths were monitored weekly from
      early March to mid-November near Lubbock and Halfway, two prominent cotton
      production areas in the Texas High Plains region. Based on trap captures, the
      bollworm-budworm complex consisted of approximately 98% bollworms and
      approximately 2% tobacco budworms. Seasonal activity patterns varied between
      location for bollworm but not for tobacco budworm. The 14-yr average (+/- SE)
      bollworm moth abundance (moths per trap per week) at Lubbock was significantly
      higher (226.5 +/- 10.4) compared with that at Halfway (153.7 +/- 8.1).
      Correlation analyses showed a significant positive relationship between moth
      abundance and average weekly temperatures, whereas a significant negative
      relationship was observed between moth abundance and average weekly wind velocity
      for both species. Analyses also showed a positive correlation between moth
      abundance and cumulative degree-days (> 0.0 degrees C) from 1 January. A strong
      positive relationship was observed between moth abundance and weekly average
      precipitation for both species. Average weekly abundances were positively
      correlated between adjacent months during most of the active cotton fruiting
      season (June-September). However, the relationship between populations that
      contributed to the overwintering generation and the following spring populations
      varied between species and study sites. Nevertheless, data from this study
      indicated that late-season moth catches could be indicative of the dynamics of
      the early-season moth catches the following year in the High Plains. The mean
      population abundance curve based on 14-yr averages showed two bollworm population
      peaks at Lubbock, but only one peak at Halfway. Separate degree-day-based models
      were developed to describe long-term seasonal abundance patterns of bollworm
      moths for the Lubbock and Halfway sites.

PMID- 15154498
TI  - Method for quantitative sampling of fungus gnat larvae in soilless growing media.
AB  - A simple method is described for separating fungus gnat larvae from soilless
      growing media. Samples are first fractionated by water flotation with an inverted
      flask procedure and then the sediment is degassed under reduced air pressure and
      fractionated in magnesium sulfate (MgSO4) solution (density of 1.12 g cm(-3)).
      Fungus gnat larvae with only a small amount of contaminating debris are recovered
      from the surface of the MgSO4 solution for immediate counting or for preservation
      in alcohol. In evaluations of different commercial soilless growing media with a
      range of components, two repetitions of the water flotation step eliminated 20
      40% of the dry weight of samples and virtually all of the perlite from further
      processing. Repeating both the water and MgSO4 flotations a third time only
      marginally improved the recovery of larval fungus gnats, Bradysia sp. nr.
      coprophila, added to pasteurized media. Extraction efficiency differed between
      instars and, to a lesser extent, between different types of media. Across three
      commercial soilless media tested, recovery was 24-33% for first, 68-85% for
      second, 85-95% for third, and 98-100% for fourth instars. Within combinations of
      media and instar, recovery was consistent. With this method, a 400-cm3 sample can
      be processed and be ready for counting in 1-1.5 h; samples can also be processed
      in batches or in assembly-line manner to process many samples per day. The method
      may also prove useful for quantitative recovery of shore fly larvae, thrips
      pupae, and other arthropods from soilless growing media.

PMID- 15154499
TI  - Population patterns of Mexican corn rootworm (Coleoptera: Chrysomelidae) adults
      indicated by different sampling methods.
AB  - The Mexican corn rootworm, Diabrotica virgifera zeae Krysan & Smith, is a serious
      pest of corn, Zea mays L., in several areas of Texas. Recent demonstrations of
      areawide adult control suggest this tactic has promise for rootworm management,
      but additional information regarding treatment thresholds and sampling
      methodology is needed. In 2000 and 2001 we examined the influence of distance
      into the field on rootworm captures by CRW and Pherocon AM traps, the fidelity of
      trap captures to population estimates from visual counts of beetles on plants
      (whole plant samples), and the seasonal population patterns indicated by each
      sampling method. Only the CRW trap consistently indicated reduced trap captures
      at the field margin compared with other distances. However, trends for the AM
      trap and whole plant samples suggested sampling on the field margin should be
      avoided. Population estimates at other distances into the field (2-30 m) were
      usually statistically similar. Thus, monitoring does not require trap placement
      far into the field. Both trap types indicated population peaks after flowering in
      corn, whereas plant samples indicated peak populations during tasseling and
      flowering. Both the CRW trap and plant samples showed the proportion of female
      beetles increased as the season progressed, but the CRW trap underestimated the
      proportion of females until after flowering. Regressions relating captures by
      traps to counts from plant samples indicated efficiency of both traps increased
      with increasing plant development. Our findings should increase acceptance of the
      CRW trap by producers and consultants and provide a rationale for development of
      improved, plant growth stage-specific treatment thresholds.

PMID- 15154500
TI  - Mortality of eggs of stored-product insects held under vacuum: effects of
      pressure, temperature, and exposure time.
AB  - Low pressure applied to a commodity creates a low-oxygen atmosphere that can be
      effective to control stored-product insects. Previous work determined that eggs
      of several species of stored-product insects were among the most tolerant life
      stages to low pressure. The current study was conducted to determine the
      mortality of eggs in response to various pressures, temperatures, and exposure
      times. An initial experiment determined that the sensitivity of eggs to vacuum
      varied with their age. Eggs of Plodia interpunctella (Hubner) were most sensitive
      to low pressure when they were 3 or 48 h old, whereas those of Rhyzopertha
      dominica (F.) were most sensitive at 12 and 120 h of age. In subsequent
      experiments, eggs of Cadra cautella (Walker), P. interpunctella, R. dominica, and
      Tribolium castaneum (Herbst) were exposed to pressures of 50, 75, 100, 200, and
      300 mmHg in glass chambers at 5, 15, 22.5, 30, and 37.5 degrees C for times
      ranging from 12 to 168 h. Time-mortality data were subjected to probit analyses
      and lethal dose ratios were computed to determine differences in lethal time
      values among species across the 25 low pressure-temperature combinations for each
      species. In all four species the mortality of eggs increased with increasing
      exposure time and temperature. Low temperatures and high pressures were the least
      effective conditions for killing eggs, compared with high temperatures combined
      with low pressures in all species investigated. These results provide important
      guidelines for developing treatment schedules for disinfestation of commodities
      on a commercial scale.

PMID- 15154501
TI  - Attractancy and toxicity of an attracticide for Indianmeal moth, Plodia
      interpunctella (Lepidoptera: Pyralidae).
AB  - Plodia interpunctella (Hubner) is a serious and widespread postharvest pest on
      cereal products, dried fruits, candy, and pet food. Due to the strong positive
      anemotactic flight response of P. interpunctella males to the main component of
      the female-produced pheromone [(Z,E)-9,12-tetradecadienyl acetate, herein
      referred to as ZETA], we evaluated the potential of an attracticide for this
      pest, in which ZETA as attractant was combined with permethrin as the killing
      agent. Two concentrations of ZETA [0.16 and 0.32% (wt:wt)] and five
      concentrations of permethrin [0, 3, 6, 12, and 18% (wt:wt)] were incorporated
      into Last Call gel (10 different permethrin:ZETA combinations). All attracticide
      gels were evaluated in a toxicity test, in which either the tip of a leg or an
      antenna of a virgin P. interpunctella male was touched < 3 s into a dot of
      attracticide gel. These males were subsequently transferred to jars with virgin
      females. The toxicity test showed that a brief and gentle contact of P.
      interpunctella males with attracticide gel containing 3-18% permethrin caused a
      significant reduction in mating and killed males moths within 24 h. A wind tunnel
      test was conducted to evaluate the flight responses of P. interpunctella males to
      the same 10 attracticide gels. Male moths displayed significantly higher levels
      of positive anemotactic flight and more males made contact with the attracticide
      gel when the ZETA concentration was 0.16% compared with 0.32%. P. interpunctella
      males showed no signs of repellency to permethrin concentrations within a range
      of 0-18% in the attracticide gel. Three densities of P. interpunctella pairs were
      released into small warehouse rooms, and we found that the attracticide gel
      suppressed oviposition when the moth density was at a low level, but it was
      ineffective when the moth density exceeded one male-female pair per 11.3 m3.

PMID- 15154502
TI  - Susceptibility of potato tuber moth (Lepidoptera: Gelechiidae) to postharvest
      gamma irradiation.
AB  - Gamma irradiation doses applied to inhibit potato sprouting were tested against
      potato tuber moth larval and pupal stages. Young larvae and pupae were more
      susceptible to irradiation injuries than older ones. When larvae of different
      ages were exposed to doses > or = 100 Gy, only 13-35% pupated, but no adult
      emergence was obtained. The exposure of 1-1.5- or 3-3.5-d-old pupae to 150 Gy
      induced high level of sterility and remarkable reduction in female mating ability
      and fecundity, whereas the reduction was less noticeable for 5-5.5-d-old pupae.
      Postharvest gamma irradiation of potatoes could be considered as an efficient
      control approach against potato tuber moth larval and pupal infestations.

PMID- 15154503
TI  - Water solutions of boric acid and sugar for management of German cockroach
      populations in livestock production systems.
AB  - Pest management in confinement swine production relies primarily on calendar
      based applications of broad-spectrum insecticides. However, regulatory
      restrictions imposed by the U.S. Food Quality Protection Act of 1996, the large
      financial obligation of pesticide registration, and development of insecticide
      resistance have led to a renewed search for alternative control methods. Boric
      acid dust has long served as an insecticide in urban pest management and has been
      shown an effective alternative for use in sensitive environments such as swine
      production. However, dust formulations are difficult to apply and require
      specialized equipment. The purpose of this study was to evaluate the efficacy of
      liquid baits containing boric acid for the control of German cockroaches in a
      commercial swine nursery. Bait, consisting of 1 or 2% boric acid and 0.5 M
      sucrose, was deployed in 21 bait delivery tubes per room. Results of a 2-yr study
      showed significant reductions in cockroach populations. When baits were withdrawn
      in the summer, the cockroach population increased significantly faster than when
      the baits were removed during the winter. These data indicate that liquid
      formulations of boric acid effectively reduce the burden of cockroach infestation
      in swine production. This approach should have applications in structures in
      other urban and agricultural environments.

PMID- 15154504
TI  - [The importance of the prenatal life period].
AB  - This paper describes the bi-directional influences or transactions between four
      levels (genetic activity, neural activity, behaviour and environment) that lead
      to the phenotypical variation, in a probabilistic way. We give an overview of the
      current scientific knowledge about these transactions in the prenatal life period
      and describe the inherent risks. Prenatal development is briefly described. We
      then consider the mechanism of genetic expression and the relationship between
      genotype and phenotype. Finally a description of recent developments and research
      findings is given of the discipline of behavioural teratology, which is related
      to the discipline of developmental psychopathology.

PMID- 15154505
TI  - [Enuresis: pathogenesis, diagnostics, and interventions].
AB  - This review summarizes the current scientific knowledge on enuresis. Enuresis is
      one of the most common disorders in childhood. New conclusions on classification,
      aetiology, clinical diagnostics and therapy could be drawn in the past years.
      Thus, recent results have shown that the previous classification of enuresis into
      nocturnal, diurnal and diurnal and nocturnal forms which is suggested by DSM-IV
      and ICD-10 is not sufficient. Daytime wetting consists of a heterogeneous group
      of syndromes, which should be considered as functional urinary incontinence.
      Primary nocturnal enuresis is mainly caused by biological factors. In contrast,
      psychosocial factors play an important role in the manifestation of the disease,
      especially in secondary enuresis. Diagnostical and therapeutical concepts have to
      consider the heterogeneity of this disorder. Evaluation studies were supported by
      effective intervention programs for nocturnal enuresis. But beneficial effects of
      treatments for functional urinary incontinence were not confirmed.

PMID- 15154506
TI  - [Success of treatment, experience of treatment, and satisfaction with treatment
      from the perspective of patients, parents, and therapists--results of an
      evaluative study on inpatient treatment in child and adolescent psychiatry].
AB  - In spite of the high importance of subjective opinions as essential evaluation
      criteria there are hardly any studies available, dealing with the research of
      subjective judgements made by children and adolescent patients in relation to
      their inpatient treatment, and comparison with the evaluation of their parents.
      The evaluative study on an age-group random sample survey (n=95) of patients and
      parents at the Department of Child and Adolescent Psychiatry at the University of
      Heidelberg includes success of treatment, experience of treatment and
      satisfaction with treatment by means of specially constructed and parallelized
      questionnaires for patients, parents and therapists. Apart from the extent of
      subjectively experienced changes in precisely defined success variables, not only
      agreements and differences were studied, but also connections between success of
      treatment, experience of treatment and satisfaction with treatment as well as
      influences of success variables and experience variables on treatment
      satisfaction. Parents', patients' and therapists' evaluations of the treatment in
      regard of most success variables were all positive. At the end of treatment a
      perspective convergence was noticeable in some variables. The pressure on the
      parents requires special therapeutic attention. In the sense of therapy
      evaluation the change in the way the problem was viewed proved to be a worthwile
      success criterium. From the patients' and parents' point of view the change in
      the problem "as a whole" is mainly characterized by a positive change in
      emotional disposition. The therapeutic atmosphere and organisation of therapeutic
      relationships were highly appreciated by patients and parents. All in all
      patients, parents and therapists were highly satisfied with inpatient treatment.
      The correlations found between the grade of success, experience of treatment and
      satisfaction with treatment were clearly positive. On the patients' side
      treatment satisfaction was dictated more by their experiences during the
      treatment, whereas on the parents' side the success of treatment proved to be the
      stronger factor.

PMID- 15154507
TI  - [What is helpful for kids with headache?--Qualitative analysis of systemic family
      interviews at the end of a solution and resource oriented group therapy for
      children and adolescents with primary headache].
AB  - Over the last few years, the prevalence rate of primary headache in childhood has
      increased significantly. Children suffering from headache can find a way to live
      without or with as few headache as possible by taking advantage of their
      individual resources. Headache afflicting children can be a considerable burden
      for the children's families and their social environment. Vice versa, these
      social systems also have a decisive influence on the child's suffering. The study
      submitted deals with the question which resources--concerning the treatment of
      headache--children, adolescents and their families were able to discover and/or
      further develop in the context of a resource-oriented and solution-oriented
      outpatient group and family treatment program, and which coping strategies they
      found to be especially helpful. For this purpose, systematic family interviews of
      n=39 families were evaluated. Dealing with headache, the notion of independence
      plays a decisive role--both for children and their parents.

PMID- 15154508
TI  - Transport and distribution of lindane and simazine in a riverine environment:
      measurements in bed sediments and modelling.
AB  - Aquatic sediments often remove hydrophobic contaminants from fresh waters. The
      subsequent distribution and concentration of contaminants in bed sediments
      determines their effect on benthic organisms and the risk of re-entry into the
      water and/or leaching to groundwater. This study examines the transport of
      simazine and lindane in aquatic bed sediments with the aim of understanding the
      processes that determine their depth distribution. Experiments in flume channels
      (water flow of 10 cm s(-1)) determined the persistence of the compounds in the
      absence of sediment with (a) de-ionised water and (b) a solution that had been in
      contact with river sediment. In further experiments with river bed sediments in
      light and dark conditions, measurements were made of the concentration of the
      compounds in the overlying water and the development of bacterial/algal biofilms
      and bioturbation activity. At the end of the experiments, concentrations in
      sediments and associated pore waters were determined in sections of the sediment
      at 1 mm resolution down to 5 mm and then at 10 mm resolution to 50 mm depth and
      these distributions analysed using a sorption-diffusion-degradation model. The
      fine resolution in the depth profile permitted the detection of a maximum in the
      concentration of the compounds in the pore water near the surface, whereas
      concentrations in the sediment increased to a maximum at the surface itself.
      Experimental distribution coefficients determined from the pore water and
      sediment concentrations indicated a gradient with depth that was partly explained
      by an increase in organic matter content and specific surface area of the solids
      near the interface. The modelling showed that degradation of lindane within the
      sediment was necessary to explain the concentration profiles, with the optimum
      agreement between the measured and theoretical profiles obtained with
      differential degradation in the oxic and anoxic zones. The compounds penetrated
      to a depth of 40-50 mm over a period of 42 days.

PMID- 15154509
TI  - Visualisation of the uptake of two model xenobiotics into bean leaves by confocal
      laser scanning microscopy: diffusion pathways and implication in phloem
      translocation.
AB  - The diffusion of two fluorescent dyes, Oregon Green 488 (Oregon Green) and
      Rhodamine B into the leaves of broad bean (Vicia faba L) plants was studied to
      simulate the foliar uptake process of pesticides. The uptake rate of these model
      xenobiotics into bean foliage was measured using a standard leaf surface wash-off
      method. Diffusion into leaf tissues was visualised in vivo by confocal laser
      scanning microscopy (CLSM). The moderately lipophilic dye (Rhodamine B) showed
      faster uptake than the hydrophilic one (Oregon Green), despite the former being a
      larger molecule. While no distinct channels or domains for preferential entry of
      any of the dyes could be detected in the cuticle layer by CLSM, two different
      diffusion patterns were identified for the movement of these two dyes after
      traversing the cuticle. Upon desorption from the cuticle, Rhodamine B diffused
      extensively into the vacuole of the epidermal cells. Further transport of this
      dye from the epidermal cells to the mesophyll cells was not observed. In
      contrast, Oregon Green was found in the epidermal cell walls and cytoplasm, and
      was also present in the mesophyll cells. Examination of the petioles of the
      treated leaves revealed that, once absorbed, Oregon Green moved readily out of
      the treated leaf, whereas Rhodamine B did not show any phloem translocation. It
      is proposed that these two different diffusion characters may be responsible for
      the contrasting phloem mobility of the two xenobiotics. The results are discussed
      in relation to the current knowledge on the uptake, translocation and efficacy of
      pesticides as influenced by their properties.

PMID- 15154510
TI  - Uptake, translocation and bioavailability of imidacloprid in several hop
      varieties.
AB  - The neonicotinoid insecticide imidacloprid is the most important insecticide in
      hop cultivation in Germany. A laboratory study was undertaken to investigate its
      systemic properties and translaminar bioavailability in hop leaves. Radiolabelled
      [methylene-14C]imidacloprid was applied either alone or in combination with
      different additives onto leaves of several hop varieties. Uptake and
      translocation were evaluated 1 and 7 days after foliar application under
      greenhouse conditions. The uptake of imidacloprid into hop leaves was most
      pronounced in the first 24 h after application and only negligible amounts were
      taken up after this period. Significant differences in the quantitative uptake
      occurred when imidacloprid was combined with additives, such as Amulsol, Genapol
      C-100, Hasten and LI 700. The uptake of imidacloprid applied without additives
      was less than 10% 7 days after application, whereas the combination with LI 700
      provided 70-80% uptake. Genapol C-100 and Amulsol induced considerable
      phytotoxicity at the application site. Comparing hop varieties revealed
      differences up to twofold in foliar penetration of imidacloprid. The translaminar
      and acropetal bioavailability of imidacloprid foliarly applied to hop leaves was
      determined by a laboratory bioassay using the damson hop aphid, Phorodon humuli
      (Schrank). Significantly higher mortality was observed with laboratory
      formulations containing imidacloprid and the additive LI 700. In contrast to
      these results from systemic tests, contact mortality at the application site was
      constantly high over the testing period of 7 days, highlighting the importance of
      this mode of entry for aphid intoxication.

PMID- 15154512
TI  - Comparison of anti-feedant and insecticidal activity of nimbin and salannin photo
      oxidation products with neem (Azadirachta indica) limonoids.
AB  - Photo-oxidation of the neem limonoids nimbin and salannin with UV light in the
      presence of oxygen gives two isomeric lactone products per limonoid, nimbinolide
      and isonimbinolide, and salanninolide and isosalanninolide, respectively. When
      compared in insect tests with the important limonoids of neem seeds,
      azadirachtin, nimbin and salannin, isonimbinolide and isosalanninolide show
      activity greater than that of nimbin or salannin and in some respects show
      activity approaching that of azadirachtin. The photo-oxidation products were
      tested for anti-feedant activity and toxicity against larvae of three species of
      Lepidoptera, Spodoptera littoralis (Boisd), Spodoptera frugiperda (FE Smith) and
      Helicoverpa armigera (Hubner) and nymphs of the locusts Schistocerca gregaria
      (Forskal) and Locusta migratoria (L).

PMID- 15154511
TI  - Prediction of field atrazine persistence in an allophanic soil with Opus2.
AB  - A modified version of the model Opus was applied to measurements of soil water
      dynamics and atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine)
      persistence in a Bruntwood silt loam soil (Haplic Andosol, FAO system) in
      Hamilton, New Zealand. The modified model, Opus2, is briefly described and
      parameter estimation for the simulations is discussed. Soil water dynamics were
      more accurately described by applying measured soil hydraulic properties than by
      estimating them using pedotransfer functions. A parameter sensitivity analysis
      revealed that degradation was the most relevant process in simulating pesticide
      behaviour by Opus2. The Arrhenius equation incorporated in Opus2 did not
      correctly describe the effect of temperature on degradation rates obtained at 10,
      20 and 30 degrees C. However, as the Arrhenius coefficient is a very sensitive
      parameter and soil temperature variation was relatively narrow in the field, the
      Arrhenius coefficient was approximated from the laboratory study. The simulation
      results obtained were superior to modelling at constant temperature. Field
      measured persistence of atrazine in the topsoil was underpredicted using the half
      life determined in the laboratory at 10 degrees C. Modelling with a lag phase
      followed by accelerated degradation by use of a sigmoidal degradation equation in
      Opus2 significantly improved the modelling results. Nevertheless, degradation
      processes in the laboratory under controlled conditions did not accurately
      represent field dissipation, however well the laboratory degradation data could
      be described by simple kinetic equations. The study indicates the importance of
      improving field techniques for measuring degradation, and developing laboratory
      protocols that yield degradation data that are more representative of pesticide
      dynamics in field soils.

PMID- 15154513
TI  - Synergism of insecticides provides evidence of metabolic mechanisms of resistance
      in the obliquebanded leafroller Choristoneura rosaceana (Lepidoptera:
      Tortricidae).
AB  - The interactions between six insecticides (indoxacarb, cypermethrin,
      chlorpyrifos, azinphosmethyl, tebufenozide and chlorfenapyr) and three potential
      synergists, (piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF)
      and diethyl maleate (DEM)) were studied by dietary exposure in a multi-resistant
      and a susceptible strain of the obliquebanded leafroller, Choristoneura rosaceana
      (Harris). The synergists did not produce appreciable synergism with most of the
      insecticides in the susceptible strain. Except for tebufenozide, PBO synergized
      all the insecticides to varying degrees in the resistant strain. A very high
      level of synergism by PBO was found with indoxacarb, which reduced the resistance
      level from 705- to 20-fold when PBO was administered alone and to around 10-fold
      when used in combination with DEF. DEF also synergized indoxacarb, cypermethrin,
      chlorpyrifos, azinphosmethyl and tebufenozide in the resistant strain. DEM
      produced synergism of indoxacarb, chlorpyrifos, azinphos-methyl and chlorfenapyr
      in the resistant strain. DEM was highly synergistic to cypermethrin, and to some
      extent to tebufenozide in both the susceptible and resistant strains equally,
      implying that detoxification by glutathione S-transferases was not a mechanism of
      resistance for these insecticides. The high level of synergism seen with DEM in
      the case of cypermethrin may be due to an increase in oxidative stress resulting
      from the removal of the antioxidant, glutathione. These studies indicate that
      enhanced detoxification, often mediated by cytochrome P-450 monooxygenases, but
      with probable esterase and glutathione S-transferase contributions in some cases,
      is the major mechanism imparting resistance to different insecticides in C.
      rosaceana.

PMID- 15154514
TI  - Genes similar to naphthalene dioxygenase genes in trifluralin-degrading bacteria.
AB  - Trifluralin (alpha,alpha,alpha-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine) is
      a dinitroaniline compound which was first produced in the 1960s and has been used
      extensively as an agricultural herbicide. There are a few publications on the
      biodegradation of this xenobiotic compound, but to our knowledge nothing has been
      documented on the genetic aspects of its catabolism. In this article, we report
      the analysis of DNA isolated from bacteria previously shown to degrade
      trifluralin, using as probes the catabolic genes ndoB, todC, xyIX, catA and xyIE
      which encode the enzymes naphthalene 1,2-dioxygenase, toluene dioxygenase,
      toluate 1,2-dioxygenase, catechol 1,2-dioxygenase and catechol 2,3-dioxygenase
      respectively. Using PCR and hybridization analysis, the strong hybridization of
      the ndoB gene with DNA extracted from four trifluralin-degrading isolates was
      demonstrated, although none of them was able to degrade naphthalene, as indicated
      by the 'clear zone' test. The results indicated the presence in these bacteria of
      a dioxygenase gene, whose product could act on trifluralin as its principal
      substrate, or fortuitously, by cometabolism. This is the first publication on
      genes in trifluralin-degrading bacteria.

PMID- 15154515
TI  - Molluscicidal activity of vulgarone B against ram's horn snail (Planorbella
      trivolvis).
AB  - The ram's horn snail (Planorbella trivolvis (Say)) is an intermediate host for a
      digenetic trematode (Bolbophorus confusus (Krause) Dubois) that has recently been
      discovered to be a significant problem in commercial channel catfish (Ictalurus
      punctatus Raf) production ponds in the Mississippi Delta region in the USA. In
      these catfish ponds, the digenetic life cycle of this parasitic trematode
      involves two intermediate hosts, the ram's horn snail and the channel catfish,
      and the final host, the American white pelican (Pelecanus erythrorhynchos
      Gmelin). One approach to eradicate this problem is to disrupt the life cycle of
      the parasitic trematodes by eliminating the snails. During our search for natural
      product-based molluscicides to control the snails in the catfish ponds, vulgarone
      B, isolated from the steam distillate of the aerial parts of the plant Artemisia
      douglasiana Besser (Asteraceae), was found to be active towards the snails with a
      LC50 of ca 24 microM. Channel catfish toxicity studies indicated a LC50 of ca 207
      microM. Vulgarone B may be an environmentally acceptable alternative for snail
      control in aquaculture.

PMID- 15154516
TI  - Toxicity of indoxacarb to two species of predacious mites and a predacious mirid.
AB  - Indoxacarb is a novel oxadiazine pro-insecticide that has no toxic effects on the
      adults, fecundity and eclosion of Amblyseius fallacis (Garman), a predacious
      phytoseiid, or Agistemus fleschneri Summers, a predacious stigmaeid. It is toxic
      to Hyaliodes vitripennis (Say), a predacious mirid that has been reported from
      several Quebec orchards where IPM programs are used. The LC50 for this mirid is
      about one-half of the recommended dose (0.054 g AI litre(-1)) of indoxacarb for
      apple orchards. Following an application, the intoxicated mirids remained
      motionless as their prolegs and posterior had paralyzed. Twenty-four hours later,
      they appeared smaller, shrunken and severely desiccated.

PMID- 15154517
TI  - Fipronil modulation of GABAA receptor single-channel currents.
AB  - Fipronil is the first phenylpyrazole insecticide introduced for pest control.
      Although fipronil is known to inhibit GABA receptors, the detailed mechanism of
      action remains to be seen. In order to elucidate the mechanism of fipronil
      interaction with the mammalian GABAA system, single-channel patch clamp
      experiments were performed using rat dorsal root ganglion neurons. The amplitude
      of main conductance state (27pS) current was not significantly altered by co
      application of 10 microM fipronil and 10 microM GABA. The histograms of open time
      distribution were fitted to a sum of three exponential functions. After
      application of 10 microM fipronil, the proportion of the fastest component
      increased slightly and that of the slowest component decreased slightly. Thus,
      the mean open time was decreased from 11.4 ms to 7.8 ms by fipronil. The
      histograms of closed time distribution were fitted to a sum of four exponential
      functions. Fipronil 10 microM prolonged the slowest time constant resulting in a
      prolongation of the mean closed time from 29.7 ms to 52.8 ms. Thus, the frequency
      of channel openings was reduced. Thus, the fipronil suppression of GABA-induced
      whole-cell currents is caused in part by decreases in the channel open time and
      the frequency of channel openings.

PMID- 15154518
TI  - Novel 3,3a,5,9b-tetrahydro-2H-furo[3,2-c][2] benzopyran derivatives: synthesis of
      chiral glycol benzyl ether herbicides.
AB  - Novel tricyclic 3,3a,5,9b-tetrahydro-2H-furo[3,2-c][2]benzopyran (TFB)
      derivatives were synthesized, and their herbicidal activities were elucidated.
      They were synthesized from D-glucose as a natural chiral source. The formation of
      the TFB skeleton was achieved by a Friedel-Crafts type intramolecular cyclization
      of methyl 5-deoxy-2,3-O-dibenzyl-5-C-methyl-D-xylofranosides. The intramolecular
      cyclization was dependent upon the electronic effects of the substituents at the
      C-2 benzyloxy group of methyl xylofranosides. Some TFBs exhibited a remarkable
      herbicidal activity to annual paddy weeds, such as Echinochloa sp, without injury
      to the rice.

PMID- 15154519
TI  - Availability of pesticide-treated seed on arable fields.
AB  - A study of the availability of pesticide-treated seed on arable fields was
      performed. The research was carried out in three different areas of The
      Netherlands (soil types ranging between sand and heavy clay) and included the
      following topics: drilling techniques, soil conditions, location on the field and
      spillage. The results show that there is a large variation among the various
      crops in the percentage of seed remaining on the soil surface. This is mainly
      caused by differences in drilling techniques and soil conditions. The percentage
      of surface seeds after standard drilling is approximately four times higher than
      after precision drilling. The best correlation for the impact of soil conditions
      was found for the overall measure of clod weight. Large differences in seed
      densities (factor of 3.5) were found between the headland and the field centre.
      Spillage occured in most crops investigated, with an average of two spills per
      field. Based on the field data it is recommended to use in the current risk
      assessment for birds and mammals the following percentages of seed remaining on
      the soil surface: 0.5% for precision drilling, 3.3% for standard drilling in
      spring and 9.2% for standard drilling in autumn.

PMID- 15154520
TI  - Comparing greenhouse sprayers: the dose-transfer process.
AB  - Three sprayers were evaluated for their affect on retention and efficacy: a
      carbon dioxide powered high-volume sprayer, a DRAMM coldfogger, and an
      Electrostatic Spraying Systems (ESS) sprayer with air-assistance. The active
      ingredients used were spinosad and azadirachtin. The plant canopy was constructed
      in the greenhouse using potted soybeans (Glycine max (L) Merrill cr Pioneer
      9392). Application efficacy with spinosad was assessed using thrips [Western
      flower thrips, Frankliniella occidentalis (Pergande)] and mite (two-spotted
      spider mite, Tetranychus urticae Koch) abundance on shoots and leaves.
      Application efficacy with azadirachtin was assessed using thrips and aphid
      (soybean aphid, Aphis glycines Matsumura) abundance on shoots and leaves. The
      atomization characteristics of each sprayer were measured using an Aerometrics
      phase/Doppler particle analyzer (PDPA) 100-1D. The results of four tests are
      presented. Two tests used each sprayer according to manufacturer recommendations.
      These are 'recommended volume' tests that confound differences in toxicant
      distribution caused by the sprayer with differences caused by changes in
      application volume. The other two tests were 'constant volume' tests in which all
      three sprayers were used to deliver the same application volume. Both types of
      test gave differences between sprayers in retention of toxicant, but only the
      recommended volume tests showed significant effects of the sprayers on pest
      abundance. We attribute this difference to the role played by changing
      application volumes in the dose-transfer process. The constant-volume tests
      showed that application equipment influences efficacy.

PMID- 15154521
TI  - The relationship between the chemical composition of three essential oils and
      their insecticidal activity against Acanthoscelides obtectus (Say).
AB  - The chemical composition of the essential oils isolated from various parts of
      three Greek aromatic plants (Lavandula hybrida Rev, Rosmarinus officinalis L and
      Eucalyptus globulus Labill) collected at different seasons was determined by
      GC/MS analysis. The insecticidal action of these oils and of their main
      constituents on Acanthoscelides obtectus (Say) adults was evaluated and their
      LC50 values were estimated. All essential oils tested exhibited strong activity
      against A. obtectus adults, with varying LC50 values depending on insect sex and
      the composition of the essential oils. A correlation between total oxygenated
      monoterpenoid content and activity was observed, with oxygenated compounds
      exhibiting higher activity than hydrocarbons. Among the main constituents, only
      linalyl and terpinyl acetate were not active against A. obtectus, while all the
      others exhibited insecticidal activity against both male and female adults, with
      LC50 values ranging from 0.8 to 47.1 mg litre(-1) air. An attempt to correlate
      the insecticidal activity to the monoterpenoid's structure is presented, and the
      difference in sensitivity between male and female individuals is also explored.

PMID- 15154522
TI  - Automated multiplanar imaging: a novel approach to ultrasonography.

PMID- 15154523
TI  - History of ultrasound in animal science.

PMID- 15154524
TI  - Spectrum of high-resolution sonographic features of urinary tuberculosis.
AB  - OBJECTIVE: To evaluate the high-resolution sonographic features of urinary
      tuberculosis. METHODS: During a period of about 3 years 6 months, there were 45
      patients with sonographic features of urinary tuberculosis that was subsequently
      proved by urine culture or biopsy. The clinical symptoms, urinalysis findings,
      sonographic features, urine smear findings, and biopsy findings were recorded.
      RESULTS: The most common symptoms were dysuria and frequency of micturition.
      Sonographic features included parenchymal masses, cavities, mucosal thickening of
      the collecting system and urinary bladder, stenosis of the collecting system, a
      contracted urinary bladder, vesicoureteric reflux, and calcifications. The proof
      of tuberculosis was by urinalysis, culture, and biopsy. CONCLUSIONS: High
      resolution sonography in appropriate clinical situations is useful in diagnosis
      of urinary tuberculosis. The various high-resolution sonographic findings in
      urinary tuberculosis are illustrated. The distinguishing features are
      visualization of involvement of multiple sites and multiple stages of disease in
      the same patient.

PMID- 15154525
TI  - The influence of left renal vein entrapment on outcome after surgical varicocele
      repair: a color Doppler sonographic demonstration.
AB  - OBJECTIVE: To evaluate the impact of left renal vein entrapment on outcome after
      surgical varicocele repair using color Doppler sonography. METHODS: Eighty-four
      men had varicoceles on color Doppler sonography (2 right sided, 74 left sided,
      and 8 bilateral), which were diagnosed on the basis of a venous diameter of 3 mm
      or greater and venous retrograde flow in the pampiniform plexus of veins during
      the Valsalva maneuver or when changing from a supine to an upright position.
      Diagnosis of the left renal vein entrapment was based on the following criteria:
      antero-posterior diameter of greater than 1 cm and peak velocity of less than 15
      cm/s for the left renal vein at the mid portion and anteroposterior diameter of
      less than 0.2 cm and peak velocity of greater than 110 cm/s (or, alternatively, a
      diameter ratio and peak velocity ratio of >5) for the left renal vein between the
      aorta and superior mesenteric artery. All patients underwent surgical varicocele
      repair. In postoperative follow-up, we compared the presence of left renal vein
      entrapment with the frequency of varicocele recurrence. RESULTS: Sixteen (19%) of
      84 patients had left renal vein entrapment with a left-sided varicocele.
      Postoperatively (mean follow-up +/- SD, 19.3 +/- 11.7 months), 27 (32.2%) of 84
      had varicocele recurrence, including all 16 patients with left renal vein
      entrapment and 11 (20.1%) of 68 patients without left renal vein entrapment. The
      varicocele recurrence rate was significantly greater in patients with left renal
      vein entrapment (P < .001, Fisher exact test). CONCLUSIONS: The presence of left
      renal vein entrapment resulted in a significantly higher varicocele recurrence
      rate. Patients with varicoceles should routinely be evaluated for the presence of
      left renal vein entrapment before surgical repair.

PMID- 15154526
TI  - Sonography as a predictor of human immunodeficiency virus-associated nephropathy.
AB  - OBJECTIVE: To determine whether renal sonography can be used to predict the
      pathologic diagnosis of human immunodeficiency virus-associated nephropathy.
      METHODS: This cross-sectional study evaluated 87 human immunodeficiency virus
      positive patients who underwent both kidney biopsy and renal sonography after
      referral to the Johns Hopkins Renal Clinic from January 1995 to July 2002. Using
      a standardized measure of echogenicity, an independent blinded radiologist
      reviewed the original sonographic images. Sensitivity, specificity, positive and
      negative predictive values, receiver operating characteristic curves, and
      likelihood ratios were determined with the use of the biopsy pathologic report as
      the criterion standard. RESULTS: Thirty-four patients (39%) had biopsy-proved
      human immunodeficiency virus-associated nephropathy. A higher serum creatinine
      level, greater proteinuria, and black race were associated with human
      immunodeficiency virus-associated nephropathy, whereas age, sex, hypertension,
      and diabetes were not. Sensitivity and specificity for the highest 2 levels of
      echogenicity were 96% and 51%, respectively Sensitivity and specificity for the
      highest level of echogenicity were 40% and 95%. The likelihood ratio for the
      diagnosis of human immunodeficiency virus-associated nephropathy on the basis of
      the highest echogenicity score was 7.4 (95% confidence interval, 1.3-73.0; P =
      .006). The likelihood ratio for the lowest 2 echogenicity scores was 0.08 (95%
      confidence interval, 0.002-0.57; P = 0.003). Kidney size was not associated with
      human immunodeficiency virus-associated nephropathy status. CONCLUSIONS: This
      study provides evidence that, among patients with human immunodeficiency virus
      and kidney disease, the highest and lowest levels of sonographic echogenicity
      have diagnostic value in respectively establishing or excluding human
      immunodeficiency virus-associated nephropathy.

PMID- 15154527
TI  - Comparison of prostate-specific antigen adjusted for transition zone volume
      versus prostate-specific antigen density in predicting prostate cancer by
      transrectal ultrasonography.
AB  - OBJECTIVE: Prostate-specific antigen is an excellent tumor marker, but it is not
      specific for prostate cancer. We evaluated the efficacy of prostate-specific
      antigen adjusted for transition zone volume calculated by transrectal
      ultrasonography in predicting prostate cancer in men with intermediate prostate
      specific antigen levels of 4.1 to 10.0 ng/mL compared with prostate-specific
      antigen density. METHODS: Between June 1998 and December 2001, prostate-specific
      antigen adjusted for transition zone volume was obtained from 131 patients who
      underwent ultrasonographically guided biopsies and had prostate-specific antigen
      of 4.1 to 10.0 ng/mL. Prostate-specific antigen density was calculated by
      dividing total serum prostate-specific antigen by total prostate volume, and
      total serum prostate-specific antigen was divided by transition zone volume to
      yield prostate-specific antigen adjusted for transition zone volume. This was
      compared with prostate-specific antigen density via receiver operating
      characteristic curves. RESULTS: Of 131 patients, 34 (26%) had prostate cancer,
      and 97 (74%) had benign prostatic hyperplasia on pathologic examination. Total
      prostate volume was correlated with transition zone volume (P < .001). Mean
      prostate-specific antigen adjusted for transition zone volume and prostate
      specific antigen density were 0.71 +/- 0.25 and 0.27 +/- 0.09 ng x mL(-1) x mL(
      1) in patients with prostate cancer and 0.32 +/- 0.09 and 0.16 +/- 0.05 ng x ml(
      1) x mL(-1) in patients with benign prostatic hyperplasia. With a cutoff value of
      0.35 ng mL(-1) x mL(-1), prostate-specific antigen adjusted for transition zone
      volume had sensitivity of 82% and specificity of 84%. Receiver operating
      characteristic curve analysis showed that prostate-specific antigen adjusted for
      transition zone volume predicted biopsy outcome significantly better than
      prostate-specific antigen density (P < .05). CONCLUSIONS: Prostate-specific
      antigen adjusted for transition zone volume is more accurate than prostate
      specific antigen density in distinguishing prostate cancer from benign prostatic
      hyperplasia in men with intermediate serum prostate-specific antigen of 4.1 to
      10.0 ng/mL. Determination of transition zone volume by transrectal
      ultrasonography may be helpful for predicting the probability of positive biopsy
      results.

PMID- 15154528
TI  - Color and power Doppler sonography in the diagnosis of prostate cancer:
      comparison between vascular density and total vascularity.
AB  - OBJECTIVE: Advances in color flow Doppler (CFD) and power Doppler imaging (PDI)
      have potential for prostate cancer diagnosis. Previous reports based on
      qualitative assessment suggest that hypervascularity increases likelihood of
      prostate cancer. Our objective was to compare 2 methods of vascularity assessment
      using PDI: total vascularity (TV) and vascular density (VD). The goal was to
      determine whether quantitative Doppler vascularity correlates with the likelihood
      of prostate cancer. Quantitative measurements were compared with subjective
      visual analysis of images. METHODS: Ninety patients before biopsy had gray scale
      sonography, CFD, and PDI. Histologic analysis showed adenocarcinoma, prostate
      intraepithelial neoplasia, benign prostatic hypertrophy/prostatitis, and benign
      findings. The CFD and PDI images were analyzed for vascularity by (1) integrating
      the number of blood vessels over an imaged area (TV) and (2) integrating the
      number of vessels over a unit area of tissue (VD). Images were also assessed
      visually. VD, TV, and visual assessment were compared with one another and
      histologic findings. RESULTS: Mean volume was not different. In each pathologic
      group, vascularity extent measured by TV and VD ranged from low to high. Disease
      groups did not exhibit a substantial difference in vascularity by either
      quantitative or qualitative analyses. Regionally, central gland TV was not
      significantly more vascular than peripheral gland TV except in benign prostatic
      hypertrophy. However, peripheral gland VD was 2.5 times greater than central
      gland VD. Seventy-one percent of the 31 focal hypoechoic lesions were
      hypervascular. Only 23% were carcinoma. CONCLUSIONS: Pathologic categories were
      not separable by apparent vascular measurement. All pathologic categories showed
      low, moderate, or high vascularity; thus vascular areas by themselves did not
      distinguish cancer types, nor did focal hypervascular hypoechoic areas increase
      the likelihood of cancer. These imaging techniques provided no further resolution
      of tumor discrimination over multiple biopsies of the prostate.

PMID- 15154529
TI  - Age-related rhabdosphincter function in female urinary stress incontinence:
      assessment of intraurethral sonography.
AB  - OBJECTIVE: To assess dynamic intraurethral sonography in the diagnostic
      evaluation of the function of the rhabdosphincter in female patients with urinary
      stress incontinence in relation to patient age. METHODS: Sixty-two patients with
      clinically proved urinary stress incontinence were investigated by means of
      intraurethral sonography with a 12.5-MHz endoluminal 9F catheter. The omega
      shaped rhabdosphincter was visualized at rest and during voluntary contractions.
      Changes of muscle thickness and transducer-sphincter distance were measured and
      considered as parameters of muscle function. The intraurethral sonographic data
      were compared with results of standard urodynamic tests. RESULTS: Transducer
      sphincter distance and sphincter muscle thickness showed a significant decrease
      with positive linear dependency on patient age (P < .001). Patients with grade
      III urinary stress incontinence had complete loss of sphincter contractility. A
      negative correlation was revealed between urethral closure pressure and patient
      age. CONCLUSIONS: We found an age-related decrease in rhabdosphincter function.
      Our results suggest that the rhabdosphincter is a substantial component of the
      continence mechanism in female urinary stress incontinence. Unlike urethral
      pressure profiles, which can only reveal zones of higher intraluminal pressure,
      transurethral sonography is highly specific for measurement of the function of
      the rhabdosphincter.

PMID- 15154530
TI  - The sonographic double-track sign: not pathognomonic for hypertrophic pyloric
      stenosis; can be seen in pylorospasm.
AB  - OBJECTIVE: The "double-track" sign has previously been reported as specific for
      hypertrophic pyloric stenosis when noted on an upper gastrointestinal series. The
      sign has been noted on sonographic examinations as well. We sought to determine
      whether this sign can also be seen in cases of pylorospasm diagnosed by
      sonography, proving it not to be pathognomonic for hypertrophic pyloric stenosis.
      METHODS: The data obtained prospectively from 91 consecutive patients studied
      between 1999 and 2002 by sonography for projectile vomiting were retrospectively
      reviewed. Cases with diagnoses of hypertrophic pyloric stenosis or pylorospasm
      were reviewed for the imaging finding of the double-track sign. RESULTS: Thirty
      seven patients had a sonographic diagnosis of hypertrophic pyloric stenosis that
      was confirmed surgically. Twenty-six (70.2%) showed a sonographic double-track
      sign. Thirty-four patients had a sonographic diagnosis of pylorospasm that was
      confirmed by close clinical follow-up. Eighteen (52.9%) showed a sonographic
      double-track sign. CONCLUSIONS: The sonographic double-track sign can be seen in
      cases of pylorospasm as well as hypertrophic pyloric stenosis. It is not
      pathognomonic for hypertrophic pyloric stenosis.

PMID- 15154531
TI  - Smoking prevents the expected postprandial increase in intestinal blood flow: a
      Doppler sonographic study.
AB  - OBJECTIVE: To assess whether cigarette smoking had an effect on superior
      mesenteric artery postprandial blood flow. METHODS: Forty-six subjects were
      studied in 3 groups with Doppler sonography. Group A consisted of nonsmokers;
      groups B and C consisted of smokers. In group B, subjects were allowed to smoke
      cigarettes postprandially, whereas in group C, postprandial smoking was
      prohibited. A baseline Doppler evaluation was performed in the fasting state, and
      consecutive Doppler evaluations were performed postprandially with 30-min
      intervals for 120 minutes. Doppler sonographic measurements of the superior
      mesenteric artery, including peak systolic and end-diastolic velocities,
      resistive index, and diameter, were calculated. Statistical analysis was
      performed by analysis of variance. RESULTS: All groups showed significant changes
      with time for all parameters (P < .001 for all). The changes in time were
      significantly different at 90 and 120 minutes for peak systolic velocity, at 90
      minutes for end-diastolic velocity, and at 120 minutes for diameter between
      groups. Group B had the greatest differences. Compared with group A, changes in
      peak systolic velocity at 90 to 120 minutes were significantly lower in group B
      (P = .007 and .006, respectively), and compared with groups A and C, changes in
      end-diastolic velocity at 90 minutes (P = .006 and .004, respectively) and
      diameter at 120 minutes (P = .007 and .011, respectively) were significantly
      lower in group B. CONCLUSIONS: Smoking immediately after meals was associated
      with a superior mesenteric artery blood flow increase that was lower than
      expected, which may explain the belief that smoking reduces body weight.
      Postprandial smoking may have undesired results in patients with chronic
      intestinal ischemia.

PMID- 15154532
TI  - Venous sonography for the diagnosis of asymptomatic deep vein thrombosis in
      patients with cancer undergoing chemotherapy.
AB  - OBJECTIVE: Early detection of asymptomatic deep vein thrombosis by venous
      sonography may identify patients who may benefit from anticoagulant therapy and
      thus may prevent morbidity and mortality associated with deep vein thrombosis.
      The aim of this study was to examine the prevalence of deep vein thrombosis by
      venous sonography in asymptomatic ambulatory patients with cancer undergoing
      chemotherapy and to evaluate the correlation between procoagulant activity and
      asymptomatic deep vein thrombosis. METHODS: The study population included 62
      patients (32 with lung cancer and 30 with lymphoma) receiving chemotherapy with
      an ambulatory performance status and without clinical evidence of deep vein
      thrombosis. Bilateral venous sonographic studies of the lower extremities were
      performed, covering the femoropopliteal venous system. The D-dimer level and
      acquired activated protein C resistance were determined in the patients and in 30
      healthy control subjects. RESULTS: Sonographic evidence of deep vein thrombosis
      on the femoropopliteal axis was found in 0 (0%) of 62 patients (1-sided 95%
      confidence interval, 0%-4.8%). Acquired activated protein C resistance prevalence
      and D-dimer levels were increased in study patients compared with control
      subjects (34% versus 0%; P < .003; median, 0.72 versus 0.25 mg/L; P < .0001,
      respectively). CONCLUSIONS: Despite the procoagulant tendency, venous sonography
      did not detect asymptomatic deep vein thrombosis in patients with cancer
      undergoing chemotherapy. Thus, screening by venous sonography is not justified in
      this patient population.

PMID- 15154533
TI  - Echogenicity of B-mode sonographic images of the carotid artery: work in
      progress.
AB  - OBJECTIVE: The echogenicity of the carotid atheromatous plaque estimated from B
      mode sonographic images may be related to plaque content and has been analyzed
      with a number of techniques. The purpose of this study was to compare plaque with
      surrounding muscle tissue echogenicity and to validate the use of first-order
      mathematical descriptors as determinants of tissue echogenicity. METHODS: We
      estimated echogenicity descriptors for regions in the following 3 distinct areas
      of a typical B-mode sonographic image of a diseased carotid artery: plaque,
      blood, and sternocleidomastoid muscle. Two-dimensional B-mode sonographic images
      from 19 symptomatic and asymptomatic plaques (17 subjects) were interrogated, in
      which the following estimators were calculated: minimal, maximal, mean, and
      median gray levels, SD of gray levels, coefficient of variation, and gray level
      skewness, kurtosis, entropy, and energy. Plaque echogenicity was estimated at
      systole and diastole for studying the effect of the phase of the cardiac cycle.
      To assess the effect of different fascial tissue-muscle fiber composition on the
      first-order mathematical descriptors, we estimated echogenicity at 3 different
      sites within the muscle tissue. RESULTS: Compared with the echogenicity of
      surrounding muscle tissue, plaque echogenicity was characterized by (1)
      significantly lower (Student t test, P < .05) gray level mean, median, SD, and
      entropy; (2) significantly higher (Student t test, P < .05) coefficient of
      variation, gray level skewness, and kurtosis; and (3) similar minimal and maximal
      gray levels and gray level energy. The phase of the cardiac cycle, systole or
      diastole, did not affect the estimation of plaque echogenicity. Echogenicity was
      found to vary within the muscle tissue. The coefficient of variation was
      significantly higher in the asymptomatic plaques in the small group that was
      investigated. CONCLUSIONS: First-order statistical descriptors may be used to
      characterize atheromatous plaques and the surrounding muscle tissue.

PMID- 15154534
TI  - Intertester reliability of sonography in patellar tendinopathy.
AB  - OBJECTIVE: Intertester reliability is imperative during the sonographic
      assessment of patellar tendinopathy because hypoechoic areas can change over
      time, and repeated examination may involve multiple examiners. Given that, to our
      knowledge, it has not been reported in the literature, the objective of this
      study was to investigate the intertester reliability of sonography for the
      detection and measurement of hypoechoic areas associated with patellar
      tendinopathy. METHODS: The study cohort comprised 8 patients with clinically
      diagnosed patellar tendinopathy and 4 patients with bilateral asymptomatic
      patellar tendons. Two equally experienced musculoskeletal radiologists imaged
      both patellar tendons from each patient (n = 24). All 24 tendons were assessed on
      the same day with the use of identical sonography machines. RESULTS: The
      radiologists had 100% chance-corrected agreement for detecting 12 normal
      (hypoechoic free) and 12 abnormal (hypoechoic) tendons. All measurement data were
      normally distributed (P > .05), and a range of hypoechoic area sizes was evident.
      No statistically significant differences were found for the measurements of
      hypoechoic area, axial plane height and width, and sagittal plane height (P >
      .05). In addition, these measurements were equally highly correlated (Pearson r >
      0.87; P < .01). CONCLUSIONS: The results reported in this study suggest that the
      intertester reliability of sonography for the assessment of patellar tendinopathy
      is high. Although these results are encouraging, a small sample was analyzed, and
      this increases the probability of type II measurement error. Larger studies are
      therefore required to confirm these findings. High intertester reliability
      indicates that multiple experienced radiologists can reliably assess the same
      tendon and provides researchers with a necessary foundation for furthering
      research in tendon rehabilitation.

PMID- 15154535
TI  - Detection of soft tissue foreign bodies in the presence of soft tissue gas.
AB  - OBJECTIVE: To determine the effect of soft tissue gas on the accuracy of foreign
      body detection by realtime sonography. METHODS: This was a prospective randomized
      study using glass, metal, and bone inserted into turkey breasts to simulate human
      soft tissue foreign bodies. Air was subsequently injected around a random
      selection of the foreign bodies to simulate soft tissue gas that can accompany a
      blast or high-force injury. Using a linear transducer, physicians credentialed in
      the use of sonography were each asked to scan the breasts, identify the location
      of any foreign body, and describe whether the object located was bone, metal, or
      glass. They were also asked to describe the characteristics of the foreign body,
      including surface echogenicity, visibility, and artifacts, if any. RESULTS: The
      sensitivity for localization of each foreign body by each sonographer was 100%
      (48 of 48) and was unaffected by the presence of soft tissue gas. The accuracy of
      classifying the foreign body was poor except with bone. Glass and metal were
      often confused with each other. With the addition of soft tissue gas over the
      foreign bodies, the sensitivity of classifying the foreign body was decreased
      further from a combined 58% to 28%. The presence of soft tissue gas decreased the
      amount of reflection of the foreign body and obscured the subtle differences in
      the brightness of each foreign body, leading to a decrease in the accuracy of
      identification but not localization of the foreign body. CONCLUSIONS: In an
      experimental model, soft tissue gas does not affect the localization of soft
      tissue foreign bodies. However, correct identification of the type of foreign
      body is limited by soft tissue gas because of loss of the typical sonographic
      characteristics.

PMID- 15154536
TI  - Noninvasive estimation of the pressure gradient across stenoses using sonographic
      contrast: in vitro validation.
AB  - OBJECTIVE: Because velocity measurements to estimate the degree of arterial
      stenosis are susceptible to local and systemic factors, we aimed to investigate
      the feasibility of estimating the pressure gradient across a stenosis
      noninvasively by using sonographic contrast. METHODS: Using a gravity-fed flow
      system, a 1:4000 dilution of a contrast agent in water was circulated through
      silicone tubes that had either focal or long-segment stenoses of varying severity
      in a water bath. We measured the cross-sectional areas of the normal and stenotic
      regions with B-mode sonography and the flow velocity with spectral Doppler
      sonography and calculated the pressure gradients across the stenoses using the
      empirically derived Young mathematical model and the simplified Bernoulli
      equation. Estimated gradients were compared with those measured manometerically.
      RESULTS: Both methods yielded estimates of pressure gradients that correlated
      with measured gradients (r > 0.988). In focal and long-segment stenoses, the
      Young model yielded gradients that agreed more closely with manometerically
      measured values than the Bernoulli equation (+/- 8% versus -24%-57%). Both
      methods were highly dependent on the ability to measure the luminal cross
      sectional area. The presence of sonographic contrast in the vascular lumen
      highlighted the inner wall, allowing the accurate measurement of the luminal area
      to +/- 3.0%. CONCLUSIONS: The pressure gradient can be estimated across stenoses
      noninvasively. The Young model was more accurate than the simplified Bernoulli
      equation in this model using steady flow. Estimated gradients are highly
      dependent on the definition of the vascular lumen, a process aided by the use of
      sonographic contrast.

PMID- 15154537
TI  - Segmentation of quantitative ultrasonographic images of the calcaneus using
      elastic deformation of the flexible Fourier contour.
AB  - OBJECTIVE: This study investigated a new technique for automatic model-based
      segmentation of broadband ultrasound attenuation (BUA) images of the calcaneus.
      We determined whether this technique was able to improve osteoporotic fracture
      discrimination. METHODS: The segmentation process included 2 major steps: a model
      building stage and the automatic segmentation of new image data sets via an
      elastic deformation of contour models. Broadband ultrasound attenuation was then
      averaged within the final contour (BUAwhole). The results of the segmentation
      were validated on a database of 256 patients by comparison of the clinical
      results obtained with the automatic circular region of interest (BUAcirc)
      currently implemented on a commercially available ultrasonography unit. All
      patients were selected by the same physician, who assessed that the fractures
      were caused by bone fragility on the basis of the circumstances under which
      fractures occurred and radiologic data. RESULTS: Short-term reproducibility
      assessed in 49 women was 3.5% and 3.98% for BUAcirc and BUAwhole, respectively.
      Both BUAcirc (age-adjusted T score, -3.78; P < .0005; age-adjusted odds ratio,
      1.92; 95% confidence interval, 1.34-2.75; area under the receiver operating
      characteristic curve, 0.70) and BUAwhole (age-adjusted T score,-2.73; P < .01;
      age-adjusted odds ratio, 1.57; 95% confidence interval, 1.12-2.21; area under the
      curve, 0.67) performed equally well in discriminating healthy postmenopausal
      patients (n = 150) from those with fractures (n = 60). CONCLUSIONS: Fully
      automatic segmentation by parametrically deformable elastic models for contour
      using Fourier descriptors can be achieved with reasonable reproducibility and
      fracture risk prediction. The method is similar to existing methods (automatic
      circular region of interest); however, the new contour-based region of interest
      allows more flexible region of interest geometries and placement and potential
      adaptation to individual anatomy. The method could also possibly be extended to
      quantitative ultrasonographic imaging at different skeletal sites.

PMID- 15154538
TI  - Sonography of posterior tibialis tendon dislocation.

PMID- 15154539
TI  - Sonographic appearance of primary synovial chondromatosis of the knee.

PMID- 15154540
TI  - Sonography of a mercury foreign body in the hand.

PMID- 15154541
TI  - Sonographic appearance of subcutaneous angiolipomas.

PMID- 15154542
TI  - Endosonographic features of solitary gastric amyloidosis.

PMID- 15154543
TI  - AIUM Technical Bulletin. How to interpret the ultrasound output display standard
      for higher acoustic output diagnostic ultrasound devices: version 2.

PMID- 15154544
TI  - Sexual selection and sex linkage.
AB  - Some animal groups, such as birds, seem prone to extreme forms of sexual
      selection. One contributing factor may be sex linkage of genes affecting male
      displays and female preferences. Here we show that sex linkage can have
      substantial effects on the genetic correlation between these traits and
      consequently for Fisher's runaway and the good-genes mechanisms of sexual
      selection. Under some kinds of sex linkage (e.g. Z-linked preferences), a runaway
      is more likely than under autosomal inheritance, while under others (e.g., X
      linked preferences and autosomal displays), the good-genes mechanism is
      particularly powerful. These theoretical results suggest empirical tests based on
      the comparative method.

PMID- 15154545
TI  - Genome properties and the limits of adaptation in bacteriophages.
AB  - Eight bacteriophages were adapted for rapid growth under similar conditions to
      compare their evolved, endpoint fitnesses. Four pairs of related phages were
      used, including two RNA phages with small genomes (MS2 and Qbeta) two single
      stranded DNA phages with small genomes (phiX174 and G4), two T-odd phages with
      medium-sized, double-stranded DNA genomes (T7 and T3), and two T-even phages with
      large, double-stranded DNA genomes (T6 and RB69). Fitness was measured as
      absolute growth rate per hour under the same conditions used for adaptation. T7
      and T3 achieved the highest fitnesses, able to increase by 13 billionfold and
      three-quarters billionfold per hour, respectively. In contrast, the RNA phages
      achieved low fitness maxima, with growth rates approximately 400-fold and 4000
      fold per hour. The highest fitness limits were not attributable to high mutation
      rates or small genome size, even though both traits are expected to enhance
      adaptation for fast growth. We suggest that major differences in fitness limits
      stem from different "global" constraints, determined by the organization and
      composition of the phage genome affecting whether and how it overcomes
      potentially rate-limiting host processes, such as transcription, translation, and
      replication. Adsorption rates were also measured on the evolved phages. No
      consistent pattern of adsorption rate and fitness was observed across the four
      different types of phages, but within each pair of related phages, higher
      adsorption was associated with higher fitness. Different adsorption rate limits
      within pairs may stem from "local" constraints-sequence differences leading to
      different local optima in the sequence space.

PMID- 15154546
TI  - Intratetrad mating and the evolution of linkage relationships.
AB  - Mating among the immediate products of meiosis (intratetrad mating) is a common
      feature of many organisms with parthenogenesis or with mating-type determination
      in the haploid phase. Using a three-locus deterministic model we show that
      intratetrad mating, unlike other systems of mating, allows sheltering of
      deleterious recessive alleles even if there is only partial linkage between a
      mating locus and a load locus. Moreover, modifiers that reduce recombination
      between the load and mating-type locus will spread to fixation, even when there
      is no linkage disequilibrium between these loci in the population as a whole.
      This seeming contradiction to classical expectation is because partial linkage
      generates linkage disequilibrium among segregating loci within a tetrad, which
      then acts as the "mating unit."

PMID- 15154548
TI  - The role of diversification in causing the correlates of dioecy.
AB  - Dioecy is reported to be correlated with a number of ecological traits, including
      tropical distribution, woody growth form, plain flowers, and fleshy fruits.
      Previous analyses have concentrated on determining whether dioecy is more likely
      to evolve in lineages possessing these traits, rather than considering the
      speciation and extinction rates of dioecious lineages with certain combinations
      of traits. To address the association between species richness in dioecious
      lineages as a function of the ecological traits, we compared the evolutionary
      success (i.e., relative species richness) of dioecious focal lineages with that
      of their nondioecious sister groups. This test was repeated for the evolutionary
      success of randomly chosen nondioecious lineages (control lineages) compared with
      their nondioecious sister groups. If the possession of certain ecological traits
      enhances the evolutionary success of dioecious lineages, we predict an
      association between the presence of these traits and relative species richness in
      the former, but not latter, set of sister-group comparisons. Dioecious focal
      lineages with a higher number of these traits experienced higher evolutionary
      success in sister-group comparisons, whereas no trend was found for the control
      focal lineages. The increase in evolutionary success was especially true for
      dioecious focal lineages that had a tropical distribution or fleshy fruit. We
      discuss how these results provide strong support for differential evolutionary
      success theories for the correlations between dioecy and the ecological traits
      considered.

PMID- 15154547
TI  - Evolution of hierarchical cytoplasmic inheritance in the plasmodial slime mold
      Physarum polycephalum.
AB  - A striking linear dominance relationship for uniparental mitochondrial
      transmission is known between many mating types of plasmodial slime mold Physarum
      polycephalum. We herein examine how such hierarchical cytoplasmic inheritance
      evolves in isogamous organisms with many self-incompatible mating types. We
      assume that a nuclear locus determines the mating type of gametes and that
      another nuclear locus controls the digestion of mitochondria DNAs (mtDNAs) of the
      recipient gamete after fusion. We then examine the coupled genetic dynamics for
      the evolution of self-incompatible mating types and biased mitochondrial
      transmission between them. In Physarum, a multiallelic nuclear locus matA
      controls both the mating type of the gametes and the selective elimination of the
      mtDNA in the zygotes. We theoretically examine two potential mechanisms that
      might be responsible for the preferential digestion of mitochondria in the
      zygote. In the first model, the preferential digestion of mitochondria is assumed
      to be the outcome of differential expression levels of a suppressor gene carried
      by each gamete (suppression-power model). In the second model (site-specific
      nuclease model), the digestion of mtDNAs is assumed to be due to their cleavage
      by a site-specific nuclease that cuts the mtDNA at unmethylated recognition
      sites. Also assumed is that the mtDNAs are methylated at the same recognition
      site prior to the fusion, thereby being protected against the nuclease of the
      same gamete, and that the suppressor alleles convey information for the
      recognition sequences of nuclease and methylase. In both models, we found that a
      linear dominance hierarchy evolves as a consequence of the buildup of a strong
      linkage disequilibrium between the mating-type locus and the suppressor locus,
      though it fails to evolve if the recombination rate between the two loci is
      larger than a threshold. This threshold recombination rate depends on the number
      of mating types and the degree of fitness reduction in the heteroplasmic zygotes.
      If the recombination rate is above the threshold, suppressor alleles are equally
      distributed in each mating type at evolutionary equilibrium. Based on the
      theoretical results of the site-specific nuclease model, we propose that a nested
      subsequence structure in the recognition sequence should underlie the linear
      dominance hierarchy of mitochondrial transmission.

PMID- 15154549
TI  - The quantitative genetics of floral trait variation in Lobelia: potential
      constraints on adaptive evolution.
AB  - Although pollinator-mediated natural selection has been measured on many floral
      traits and in many species, the extent to which selection is constrained from
      producing optimal floral phenotypes is less frequently studied. In particular,
      negative correlations between flower size and flower number are hypothesized to
      be a major constraint on the evolution of floral displays, yet few empirical
      studies have documented such a trade-off. To determine the potential for genetic
      constraints on the adaptive evolution of floral displays, I estimated the
      quantitative genetic basis of floral trait variation in two populations of
      Lobelia siphilitica. Restricted maximum likelihood (REML) analyses of greenhouse
      grown half-sib families were used to estimate genetic variances and covariances
      for flower number and six measures of flower size. There was significant genetic
      variation for all seven floral traits in both populations. Flower number was
      negatively genetically correlated with four measures of flower size in one
      population and three measures in the other. When the genetic variance-covariance
      matrices were combined with field estimates of phenotypic selection gradients,
      the predicted multivariate evolutionary response was less than or opposite in
      sign to the selection gradient for flower number and five of six measures of
      flower size, suggesting genetic constraints on the evolution of these traits.
      More generally, my results indicate that the adaptive evolution of floral
      displays can be constrained by trade-offs between flower size and number, as has
      been assumed by many theoretical models of floral evolution.

PMID- 15154550
TI  - Evolution of Hsp90 expression in Tetrahymena thermophila (Protozoa, Ciliata)
      populations exposed to thermally variable environments.
AB  - Evolutionary consequences of thermally varying environments were studied in the
      ciliated protozoan Tetrahymena thermophila. Replicated lines were propagated for
      60 days, a maximum of 500 generations, in stable, slowly fluctuating (red
      spectrum), and rapidly fluctuating (blue spectrum) temperatures. The red and blue
      fluctuations had a dominant period length of 15 days and two hours, respectively.
      The mean temperature of all time series was 25 degrees C and the fluctuating
      temperatures had the same minimum (10 degrees C), maximum (40 degrees C), and
      variance. During the experiment, population sizes and biomasses were monitored at
      three-day intervals. After the experiment, carrying capacity and maximum growth
      rate were measured at low (15 degrees C), intermediate (25 degrees C), and high
      (35 degrees C) temperatures for each experimental line. Physiological changes in
      the lines were assessed by measuring the expression of stress-induced heat shock
      protein Hsp90 at 25 degrees C, 35 degrees C, and 39 degrees C. Population sizes
      and biomasses showed no differences between stable, blue, or red temperature
      treatments during the experiment. Also, after the experiment, mean carrying
      capacities and maximum growth rates were comparable in the stable, blue, and red
      temperature treatments. The expression of Hsp90 was higher in lines from the blue
      environment than in lines from the stable environment. Lines from the red
      environment had an intermediate level of Hsp90 expression. This supports the
      hypothesis that inducible thermotolerance and expression of canalizing genes can
      evolve in response to rapidly varying environments. Furthermore, we found
      correlative evidence of benefits and disadvantages of high Hsp90 expression.
      Lines with high expression of Hsp90 had an increased growth rate at the highest
      temperature when food resources were not limiting growth. At low and intermediate
      temperatures the same lines had the lowest carrying capacities.

PMID- 15154551
TI  - Genetic variability and drift load in populations of an aquatic snail.
AB  - Population genetic theory predicts that in small populations, random genetic
      drift will fix and accumulate slightly deleterious mutations, resulting in
      reduced reproductive output. This genetic load due to random drift (i.e., drift
      load) can increase the extinction risk of small populations. We studied the
      relationship between genetic variability (indicator of past population size) and
      reproductive output in eight isolated, natural populations of the hermaphroditic
      snail Lymnaea stagnalis. In a common laboratory environment, snails from
      populations with the lowest genetic variability mature slower and have lower
      fecundity than snails from genetically more variable populations. This result
      suggests that past small population size has resulted in increased drift load, as
      predicted. The relationship between genetic variability and reproductive output
      is independent of the amount of nonrandom mating within populations. However,
      reproductive output and the current density of snails in the populations were not
      correlated. Instead, data from the natural populations suggest that trematode
      parasites may determine, at least in part, population densities of the snails.

PMID- 15154552
TI  - The effect of learning on experimental evolution of resource preference in
      Drosophila melanogaster.
AB  - Learning is thought to be adaptive in variable environments, whereas constant,
      predictable environments are supposed to favor unconditional, genetically fixed
      responses. A dichotomous view of behavior as either learned or innate ignores a
      potential evolutionary interaction between the learned and innate components of a
      behavioral response. We addressed this interaction in the context of oviposition
      substrate choice in Drosophila melanogaster, asking two main questions. First,
      will learning also evolve in a constant environment in which it always pays to
      show the same choice? Second, how does an opportunity to learn affect the
      evolution of the innate (genetic) component of oviposition substrate choice? We
      exposed experimental populations to four selection regimes, involving selection
      on oviposition substrate preference (an orange versus a pineapple medium). In two
      selection regimes the flies were selected for preference either for the orange
      medium, or for the pineapple medium. In the remaining two selection regimes the
      flies were also selected for preference for either orange or pineapple, but
      additionally could use past experience (aversion learning) to decide which medium
      it paid to avoid. Lines exposed to the latter selection regimes evolved improved
      learning ability, indicating that learning may be advantageous even if the same
      behavioral response is favored every generation. Furthermore, of the two
      selection regimes that favored oviposition on the pineapple medium, the regime
      that allowed for learning led to the evolution of a stronger innate preference
      for pineapple, than the regime that did not allow for learning. In contrast, of
      the two regimes that selected for oviposition on the orange medium, the one that
      allowed for learning led to a smaller evolutionary change of the innate
      preference. Thus, an opportunity to learn facilitated the evolution of innate
      preference under selection for preference for pineapple, but hindered it under
      selection for preference for orange. We discuss possible mechanisms for this
      effect.

PMID- 15154553
TI  - A time series of evolution in action: a latitudinal cline in wing size in South
      American Drosophila subobscura.
AB  - Drosophila subobscura is geographically widespread in the Old World. Around the
      late 1970s, it was accidentally introduced into both South and North America,
      where it spread rapidly over broad latitudinal ranges. This invading species
      offers opportunities to study the speed and predictability of trait evolution on
      a geographic scale. One trait of special interest is body size, which shows a
      strong and positive latitudinal cline in many Drosophila species, including Old
      World D. subobscura. Surveys made about a decade after the invasion found no
      evidence of a size cline in either North or South America. However, a survey made
      in North America about two decades after the invasion showed that a conspicuous
      size cline had evolved and (for females) was coincident with that for Old World
      flies. We have now conducted parallel studies on 10 populations (13 degrees of
      latitude) of flies, collected in Chile in spring 1999. After rearing flies in the
      laboratory for several generations, we measured wing sizes and compared
      geographic patterns (versus latitude or temperature) for flies on all three
      continents. South American females have now evolved a significant latitudinal
      size cline that is similar in slope to that of Old World and of North American
      flies. Rates of evolution (haldanes) for females are among the highest ever
      measured for quantitative traits. In contrast, the size cline is positive but not
      significant for South or North American males. At any given latitude, South
      American flies of both sexes are relatively large; this in part reflects the
      relatively cool climate of coastal Chile. Interestingly, the sections of the wing
      that generate the size cline for females differ among all three continents. Thus,
      although the evolution of overall wing size is predictable on a geographic scale
      (at least for females), the evolution of size of particular wing components is
      decidedly not.

PMID- 15154554
TI  - Conspecific sperm precedence in sister species of Drosophila with overlapping
      ranges.
AB  - Barriers to gene flow that act after mating but before fertilization are often
      overlooked in studies of reproductive isolation. Where species are sympatric,
      such "cryptic" isolating barriers may be important in maintaining species as
      distinct entities. Drosophila yakuba and its sister species D. santomea have
      overlapping ranges on the island of Sao Tome, off the coast of West Africa.
      Previous studies have shown that the two species are strongly sexually isolated.
      However, the degree of sexual isolation observed in the laboratory cannot explain
      the low frequency (approximately 1%) of hybrids observed in nature. This study
      identifies two "cryptic" isolating barriers that may further reduce gene flow
      between D. yakuba and D. santomea where they are sympatric. First, noncompetitive
      gametic isolation has evolved between D. yakuba and D. santomea: heterospecific
      matings between the two species produce significantly fewer offspring than do
      conspecific matings. Second, conspecific sperm precedence (CSP) occurs when D.
      yakuba females mate with conspecific and heterospecific males. However, CSP is
      asymmetrical: D. santomea females do not show patterns of sperm usage consistent
      with CSP. Drosophila yakuba and D. santomea females also differ with respect to
      remating propensity after first mating with conspecific males. These results
      suggest that noncompetitive and competitive gametic isolating barriers may
      contribute to reproductive isolation between D. yakuba and D. santomea.

PMID- 15154555
TI  - Haplodiploidy as an outcome of coevolution between male-killing cytoplasmic
      elements and their hosts.
AB  - Haplodiploidy (encompassing both arrhenotoky and paternal genome elimination)
      could have originated from coevolution between male-killing endosymbiotic
      bacteria and their hosts. In insects, haplodiploidy tends to arise in lineages
      that rely on maternally transmitted bacteria for nutrition and that have
      gregarious broods in which competition between siblings may occur. When siblings
      compete, there is strong selection on maternally transmitted elements to kill
      males. I consider a hypothetical bacterial phenotype that renders male zygotes
      effectively haploid by preventing chromosome decondensation in male-determining
      sperm nuclei. By causing high male mortality, such a phenotype can be
      advantageous to the bacterial lineage. By eliminating paternal genes, it can also
      be advantageous to the host female. A simple model shows that the host female
      will benefit under a wide range of values for the efficiency of resource re
      allocation, the efficiency of transmission, and the viability of haploid males.
      This hypothesis helps to explain the ecological correlates of the origins of
      haplodiploidy, as well as such otherwise puzzling phenomena as obligate
      cannibalism by male Micromalthus beetles, reversion to diploidy by aposymbiotic
      male stictococcid scale insects, and the bizarre genomic constitution of scale
      insect bacteriomes.

PMID- 15154556
TI  - Evolution of mouthbrooding and life-history correlates in the fighting fish genus
      Betta.
AB  - The origin of and evolutionary transitions among the extraordinary diverse forms
      of parental care in teleost fish remain largely unknown. The "safe harbor"
      hypothesis predicts that the evolution from a "guarding" to a "brooding" form of
      care in teleost fish is associated with shifts in reproductive and life-history
      features such as reduced fecundity, and increased egg volume with higher parental
      investment. Robust phylogenetic hypotheses may help to identify evolutionary
      changes in key traits associated with differences in the form of parental care.
      Here, we used reconstruction of ancestral character states to study the evolution
      of the two forms of parental care, bubble nesting and mouthbrooding in the
      fighting fish genus Betta. We also applied a comparative analysis using the
      phylogenetic generalized least-squares method to test the "safe harbor"
      hypothesis by evaluating differences between the two forms of parental care in
      standard length, life-history traits, and three habitat variables. Evolutionary
      hypotheses were derived from the first molecular phylogeny (nuclear and
      mitochondrial DNA sequence data; 4448 bp) of this speciose group. Ancestral
      character state reconstructions of the evolution of the form of parental care in
      the genus Betta, using the methods of unweighted parsimony and maximum
      likelihood, are uncertain and further indicate a high rate of evolutionary
      transitions. Applying different weights for the suspected directionality of
      changes, based on the consistent phenotypic and behavioral differences found
      between bubble nesters and mouthbrooders, recurrent origin of mouthbrooding in
      the genus Betta is favored using parsimony. Our comparative analyses further
      demonstrate that bubble nesters and mouthbrooders do not have a consistent set of
      life-history correlates. The form of parental care in Betta is correlated only
      with offspring size, with mouthbrooders having significantly bigger offspring
      than bubble nesters, but is not correlated with egg volume, clutch size, and
      broodcare duration, nor with any of the three habitat variables tested. Our
      results thus challenge the general predictions of the "safe harbor" hypothesis
      for the evolution of alternative brood care forms in the fighting fish genus
      Betta.

PMID- 15154557
TI  - Twelve years of contemporary armor evolution in a threespine stickleback
      population.
AB  - Loberg Lake, Alaska was colonized by sea-run Gasterosteus aculeatus between 1983
      and 1988, after the original stickleback population was exterminated. Annual
      samples from 1990 to 2001 reveal substantial evolution of lateral plate (armor)
      phenotypes. The 1990 sample was nearly monomorphic for the complete plate morph,
      which is monomorphic in local sea-run populations; the low plate morph, which is
      usually monomorphic in local freshwater populations, was absent. By 2001, the
      frequency of completes had declined to 11%, and lows had increased to 75%. The
      partial plate morph and two unusual intermediate plate phenotypes were generally
      rare, but occurrence of the intermediates was unexpected. These intermediate
      phenotypes rarely occur in other, presumably older, polymorphic populations. When
      low morphs first appeared, they averaged 6.8 plates per side, indicating that the
      ancestral plate number of low morphs is high, and their mean has subsequently
      declined. Contemporary evolution in this population indicates that threespine
      stickleback adapt to freshwater habitats within decades after invasion from the
      ocean, and thus phenotypes in most populations are adapted to current conditions.

PMID- 15154558
TI  - AFLPs resolve phylogeny and reveal mitochondrial introgression within a species
      flock of African electric fish (Mormyroidea: Teleostei).
AB  - Estimating species phylogeny from a single gene tree can be especially
      problematic for studies of species flocks in which diversification has been
      rapid. Here we compare a phylogenetic hypothesis derived from cytochrome b (cyt
      b) sequences with another based on amplified fragment length polymorphisms (AFLP)
      for 60 specimens of a monophyletic riverine species flock of mormyrid electric
      fishes collected in Gabon, west-central Africa. We analyze the aligned cyt b
      sequences by Wagner parsimony and AFLP data generated from 10 primer combinations
      using neighbor-joining from a Nei-Li distance matrix, Wagner parsimony, and Dollo
      parsimony. The different analysis methods yield AFLP tree topologies with few
      conflicting nodes. Recovered basal relationships in the group are similar between
      cyt b and AFLP analyses, but differ substantially at many of the more derived
      nodes. More of the clades recovered with the AFLP characters are consistent with
      the morphological characters used to designate operational taxonomic units in
      this group. These results support our hypothesis that the mitochondrial gene tree
      differs from the overall species phylogeny due at least in part to mitochondrial
      introgession among lineages. Mapping the two forms of electric organ found in
      this group onto the AFLP tree suggests that posteriorly innervated electrocytes
      with nonpenetrating stalks have independently evolved from anteriorly innervated,
      penetrating-stalk electrocytes at least three times.

PMID- 15154559
TI  - Phylogeny and phylogeography of the Liolaemus darwinii complex (Squamata:
      Liolaemidae): evidence for introgression and incomplete lineage sorting.
AB  - Although mitochondrial DNA markers have several properties that make them
      suitable for phylogeographic studies, they are not free of difficulties.
      Phylogeographic inferences within and between closely related species can be
      mislead by introgression and retention of ancestral polymorphism. Here we combine
      different phylogenetic, phylogeographic, and population genetic methods to
      extract the maximum information from the Liolaemus darwinii complex. We estimate
      the phylogeographic structure of L. darwinii across most of its distributional
      range, and we then estimate relationships between L. darwinii and the syntopic
      species L. laurenti and L. grosseorum. Our results suggest that range expansion
      of these lineages brought them into secondary contact in areas where they are
      presently in syntopy. Here we present the first evidence for introgression in
      lizards from temperate South America (of L. danwinii mitochondrial DNA into L.
      laurenti and L. grosseorum), and for incomplete lineage sorting (between L.
      darwinii and L. laurenti). We show that a combination of methods can provide
      additional support for inferences derived from any single method and thus provide
      more robust interpretations and narrow the range of plausible hypotheses about
      mechanisms and processes of divergence. Additional studies are needed in this
      group of lizards and in other codistributed groups to determine if Pleistocene
      climatic changes could be a general factor influencing the evolutionary history
      of a regional biota.

PMID- 15154560
TI  - Complex growth rate evolution in a latitudinally widespread species.
AB  - The simultaneous effects of selective agents acting on somatic growth rates,
      their interactions, and their interactions with local environmental conditions
      that vary across a species' geographic range are potentially complex and poorly
      known. This is particularly true of viviparous ectotherms whose offspring may be
      adapted to the gestation environment provided by their mothers. We studied
      multiple sources of growth rate variation in a widespread, viviparous reptile,
      including the effect of the maternal environment on growth following parturition.
      Females in early pregnancy were collected from replicate populations close to the
      tropical and temperate margins of this species' range. These females completed
      gestation in either of two different, common environments designed to simulate
      the thermal and photoperiod environments at the sampling locations. Our
      experiments revealed complex growth rate evolution between the northern and
      southern extremes of Eulamprus quoyii's geographic range and local adaptation of
      growth rates to maternal environments. Unique to this study was the manifestation
      of these growth rate differences, entrained in utero, but expressed following
      parturition and maintained through to maturity despite the presence of
      compensatory growth. In addition to providing the most complete picture to date
      of the evolution of somatic growth in a viviparous ectotherm, our study suggests
      that understanding local adaptation to maternal gestation environments, in terms
      of both mean growth rates and growth rate reaction norms, could change our
      understanding of how growth rates have evolved in other viviparous ectotherms.
      Indeed, such local adaptation may provide a selective advantage in the evolution
      of viviparity.

PMID- 15154562
TI  - Age-specific reproductive success: evidence for the selection hypothesis.
AB  - Age-specific reproductive success has been demonstrated in many species. Three
      hypotheses have been raised to explain this general phenomenon: the experience
      hypothesis based on age-specific reproductive experience, the effort hypothesis
      based on age-specific reproductive effort, and the selection hypothesis based on
      progressive disappearance of phenotypes due to variation in individual
      productivity and survival. We used data from a long-term study of Leach's storm
      petrels (Oceanodroma leucorhoa) to present a single test of mutually exclusive
      predictions about the relationship between early breeding success and longevity.
      There should be no correlation between early breeding success and longevity under
      the experience hypothesis, a negative correlation under the effort hypothesis,
      and a positive correlation under the selection hypothesis. We found a significant
      (P < 0.0001) positive relationship between success in the first two breeding
      attempts and longevity in this population of long-lived seabirds, strongly
      suggesting that low-productivity parents were also less likely to survive early
      breeding. These data provide some of the strongest support to date for the
      selection hypothesis.

PMID- 15154561
TI  - Does linkage disequilibrium generate heterozygosity-fitness correlations in great
      reed warblers?
AB  - Heterozygosity-fitness correlations (HFCs) at noncoding genetic markers are
      commonly assumed to reflect fitness effects of heterozygosity at genomewide
      distributed genes in partially inbred populations. However, in populations with
      much linkage disequilibrium (LD), HFCs may arise also as a consequence of
      selection on fitness loci in the local chromosomal vicinity of the markers.
      Recent data suggest that relatively high levels of LD may prevail in many
      ecological situations. Consequently, LD may be an important factor, together with
      partial inbreeding, in causing HFCs in natural populations. In the present study,
      we evaluate whether LD can generate HFCs in a small and newly founded population
      of great reed warblers (Acrocephalus arundinaceus). For this purpose dyads of
      full siblings of which only one individual survived to adult age (i.e., returned
      to breed at the study area) were scored at 19 microsatellite loci, and at a gene
      region of hypothesized importance for survival, the major histocompatibility
      complex (MHC). By examining siblings, we controlled for variation in the
      inbreeding coefficient and thus excluded genome-wide fitness effects in our
      analyses. We found that recruited individuals had significantly higher multilocus
      heterozygosity (MLH), and mean d2 (a microsatellite-specific variable), than
      their nonrecruited siblings. There was a tendency for the survivors to have a
      more diverse MHC than the nonsurvivors. Single-locus analyses showed that the
      strength of the genotype-survival association was especially pronounced at four
      microsatellite loci. By using genotype data from the entire breeding population,
      we detected significant LD between five of 162 pairs of microsatellite loci after
      accounting for multiple tests. Our present finding of a significant within-family
      multilocus heterozygosity-survival association in a nonequilibrium population
      supports the view that LD generates HFCs in natural populations.

PMID- 15154563
TI  - Estimating sex-specific dispersal rates with autosomal markers in hierarchically
      structured populations.
AB  - A recent study suggests that sex-specific dispersal rates can be quantitatively
      estimated on the basis of sex- and state-specific (pre- vs. postdispersal) F
      statistics. In the present paper, we extend this approach to account for the
      hierarchical structure of natural populations, and we validate it through
      individual-based simulations. The model is applied to an empirical data set
      consisting of 536 individuals (males, females, and predispersal juveniles) of
      greater white-toothed shrews (Crocidura russula), sampled according to a
      hierarchical design and typed for seven autosomal microsatellite loci. From this
      dataset, dispersal is significantly female biased at the local scale (breeding
      group level), but not at the larger scale (among local populations). We argue
      that selective pressures on dispersal are likely to depend on the spatial scale
      considered, and that short-distance dispersal should mainly respond to kin
      interactions (inbreeding or kin competition avoidance), which exert differential
      pressure on males and females.

PMID- 15154564
TI  - Waiting for sympatric speciation.
AB  - While it now appears likely that sympatric speciation is possible, its generality
      remains contentious. If it really is rare, then most natural populations must not
      fit the assumptions of sympatric speciation theory. A better understanding of
      these assumptions may help identify when sympatric speciation is or is not
      likely. This paper investigates two such assumptions: that genetic variation for
      stringent assortative mating is not limiting and that females are not penalized
      for mating assortatively. Simulations demonstrate that the speed of sympatric
      speciation is very sensitive to the population's capacity for stringent
      assortative mating and is potentially extremely slow. The rapid divergence often
      thought to be a hallmark of sympatric speciation may only occur in a restricted
      area of parameter space.

PMID- 15154565
TI  - Replication at periodically changing multiplicity of infection promotes stable
      coexistence of competing viral populations.
AB  - RNA viruses are widely used to study evolution experimentally. Many standard
      protocols of virus propagation and competition are done at nominally low
      multiplicity of infection (m.o.i.), but lead during one passage to two or more
      rounds of infection, of which the later ones are at high m.o.i. Here, we develop
      a model of the competition between wild type (wt) and a mutant under a regime of
      alternating m.o.i. We assume that the mutant is deleterious when it infects cells
      on its own, but derives a selective advantage when rare and coinfecting with wt,
      because it can profit from superior protein products created by the wt. We find
      that, under these assumptions, replication at alternating low and high m.o.i. may
      lead to the stable coexistence of wt and mutant for a wide range of parameter
      settings. The predictions of our model are consistent with earlier observations
      of frequency-dependent selection in vesicular stomatitis virus and human
      immunodeficiency virus type 1. Our results suggest that frequency-dependent
      selection may be common in typical evolution experiments with viruses.

PMID- 15154567
TI  - Moral issues of surgical emergencies.

PMID- 15154566
TI  - Fecundity and MHC affects ejaculation tactics and paternity bias in sand lizards.
AB  - We demonstrate that extending copulation enhances probability of paternity in
      sand lizards and that determinants of copulation duration depend on a males'
      mating order (first or second). First males, with no information on presence of
      rivals, extend copulation when mating with a more fecund female. Second males,
      however, adjust copula duration in relation to a first male's relatedness with
      his female, which there is reason to believe can be deduced from the MHC-related
      odor of the copulatory plug. Male-female relatedness negatively influences a
      male's probability of paternity, and when second males are in a favored role
      (i.e., the first male is the one more closely related to the female), second
      males transfer larger ejaculates, resulting in higher probability of paternity.
      This result corroborates predictions from recent theoretical models on sperm
      expenditure theory incorporating cryptic female choice and sexual conflict. More
      specifically, the results conform to a "random roles" model, which depicts males
      as being favored by some females and disfavored by others, but not to a "constant
      type" model, in which a male is either favored or disfavored uniformly by all
      females in a population.

PMID- 15154568
TI  - A practical approach to ethical problems in surgical emergencies.

PMID- 15154569
TI  - Evolutionary medicine.
AB  - Nothing in biology makes sense except in the light of evolution. Evolutionary, or
      darwinian, medicine takes the view that contemporary diseases result from
      incompatibility between the conditions under which the evolutionary pressure had
      modified our genetic endowment and the lifestyle and dietary habits in which we
      are currently living, including the enhanced lifespan, the changes in dietary
      habits and the lack of physical activity. An evolutionary trait express a genetic
      polymorphism which finally improve fitness, it needs million years to become
      functional. A limited genetic diversity is a necessary prerequisite for
      evolutionary medicine. Nevertheless, search for a genetic endowment would become
      nearly impossible if the human races were genetically different. From a genetic
      point of view, homo sapiens, is homogeneous, and the so-called human races have
      only a socio-economic definition. Historically, Heart Failure, HF, had an
      infectious origin and resulted from mechanical overload which triggered
      mechanoconversion by using phylogenically ancient pleiotropic pathways.
      Adaptation was mainly caused by negative inotropism. Recently, HF was caused by a
      complex remodelling caused by the trophic effects of mechanics, ischemia,
      senescence, diabetes and, neurohormones. The generally admitted hypothesis is
      that cancers were largely caused by a combination of modern reproductive and
      dietary lifestyles mismatched with genotypic traits, plus the longer time
      available for a confrontation. Such a concept is illustrated for skin and breast
      cancers, and also for the link between cancer risk and dietary habits.

PMID- 15154570
TI  - Acute problems of the diabetic foot.

PMID- 15154572
TI  - Breast implants. A review.
AB  - Breast implants have been used for about four decades for both reconstructive and
      aesthetic purposes. In 1963, the quality of the artificial implants was
      revolutionized by the introduction of the silicone gel-filled implant. Since,
      this modern prosthesis has gone through an evolution of change and improvement
      with several types of devices with many variations and styles within each class.
      Actually, for the last three decades, approximately one million women have
      received silicone breast implants in the USA. But, in 1992, the American FDA
      banned silicone from the market, leaving saline implants as the only product
      generally available as an alternative until now. Other filler materials were
      introduced, but have never progressed beyond the experimental stage in the USA
      (in contrast with Europe). The evolution of the different implants through time,
      with their advantages and disadvantages will be discussed, but also the
      controversy on silicone implants in the USA and their suspected association with
      systemic diseases.

PMID- 15154571
TI  - Crural or pedal artery revascularisation for limb salvage: is it justified?
AB  - With the ageing of population, the incidence of limb-threatening ischemia
      increases. In chronic critical limb ischemia, peripheral arterial occlusive
      disease almost always involves infrainguinal and infragenicular vessels.
      Fortunately, recent advances in vascular surgery made arterial reconstruction of
      crural and pedal vessels possible. Should crural or pedal bypass surgery be
      offered to these frail, polyvascular patients, or is primary amputation a
      preferable treatment option in case of advanced limb-threatening ischemia? In
      order to answer this controversial question, the author analysed recent
      literature data on the feasibility and durability of infrapopliteal bypasses. The
      quality of life was also considered as an outcome measure. Finally, the cost
      effectiveness of both treatment modalities (limb-saving distal bypass versus
      primary amputation) was assessed.

PMID- 15154573
TI  - Living related liver transplantation in adults: first year experience at the
      University of Liege.
AB  - Living related liver transplantation (LRLT) in adult recipients has been recently
      developed to overcome the organ donor shortage, but LRLT leaves the healthy
      donors at risk of serious post-operative complications, or even death. The aim of
      this paper is to report the prospective evaluation of the initial experience of
      adult LRLT at the University of Liege. From March 2002 till March 2003, in a
      consecutive series of 35 adult liver transplantations, five recipients (mean age:
      51 years) underwent LRLT, including one retransplantation. Indications for
      transplantation were autoimmune hepatitis, hepatitis B virus related cirrhosis
      with hepatocarcinoma (two cases), hepatitis C virus related cirrhosis with
      hepatocarcinoma, and ischemic intrahepatic bile duct necrosis 10 years after
      primary liver transplantation. Mean age of the donors was 34 years (range: 21-53
      years). All donation cases were intra familial at first degree. The right lobe
      was used as a graft in four cases and the left lobe in one case. All right lobe
      donors developed transient hyperbilirubinemia and hypocoagulation for 4 to 6
      days. No severe complication (transfusion, bile duct fistula, reintervention,
      rehospitalization) nor significant long-term sequelae were observed in the
      donors. In the recipients, graft function was immediate, and there was no small
      for-size syndrome. One recipient developed biliary fistula treated by
      reoperation. One recipient died from invasive aspergillosis 11 days after the
      procedure. The four other recipients were alive without recurrence of the disease
      at follow-up. This report confirmed that LRLT may be a valuable alternative to
      cadaveric liver transplantation in the era of organ donor shortage. However, even
      if there was no severe complication for the donors in our preliminary experience,
      LRLT puts healthy living donors at risk of significant morbidity and even death.

PMID- 15154574
TI  - Surgical treatment of symptomatic cavernous hemangiomas of the liver.
AB  - BACKGROUND: Elective surgery for liver hemangiomas is still controversial.
      MATERIAL AND METHODS: Twenty-one patients, all symptomatic, underwent surgery for
      liver hemangiomas between August 1986 and June 2001. The primary indications for
      surgery were abdominal pain in 12 patients, pain and enlargement in 4, bleeding
      after needle biopsy in 1 and diagnostic uncertainty and suspicion of malignancy
      in 4. RESULTS: Enucleation was the choice of operation in 18 patients. Hospital
      mortality and morbidity were 0% and 9.52% respectively. Mean follow-up period was
      58.55 months (2-180). Mean hospitalization time was 15.6 days (8-75) and mean
      transfusion requirement was 2.1 units (0-18) of erythrocyte suspension. The
      median largest dimension of the major lesions was 12.71 cm (2-30). CONCLUSION:
      Elective surgery is indicated in a small subset of patients with hemangiomas
      because of abdominal pain, enlargement, diagnostic uncertainty and bleeding after
      needle biopsy. The results of surgery without any mortality and minimal morbidity
      are safe and effective. Enucleation is the preferred operation and can be
      performed rapidly and safely.

PMID- 15154575
TI  - The surgical treatment of chronic intestinal ischemia: results of a recent
      series.
AB  - Due to the rarity of the condition, large and prospective series defining the
      optimal method of digestive arteries revascularization, for the treatment of
      chronic intestinal ischemia, are lacking. The aim of this consecutive sample
      clinical study was to test the hypothesis that flexible application of different
      revascularization methods, according to individual cases, will yield the best
      results in the management of chronic intestinal ischemia. Eleven patients, of a
      mean age of 56 years, underwent revascularization of 11 digestive arteries for
      symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric
      arteries and one celiac axis were revascularized. The revascularization
      techniques included retrograde bypass grafting in 7 cases, antegrade bypass
      grafting in 2, percutaneous arterial angioplasty in 1, and arterial
      reimplantation in one case. The donor axis for either reimplantation or bypass
      grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4,
      and the celiac aorta in one case. Grafting materials included 5
      polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures
      included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean
      follow-up duration was 31 months. There was no operative mortality. Cumulative
      survival rate was 88.9% at 36 months (SE 12.1%). Primary patency rate was 90% at
      36 months (SE 11.6%). The symptom free rate was 90% at 36 months (SE 11.6%).
      Direct reimplantation, antegrade and retrograde bypass grafting, all allow good
      mid-term results: the choice of the optimal method depends on the anatomic and
      general patient's status. Associated infrarenal and renal arterial lesions can be
      safely treated in the same time of digestive revascularization. Angioplasty alone
      yields poor results and should be limited to patients at poor risk for surgery.

PMID- 15154576
TI  - Significance of antithrombin III, protein C and protein S in acute mesenteric
      ischemia patients.
AB  - It is well established that a condition of hypercoagulation due to deficiencies
      of antithrombin III, protein C and protein S may result in thrombo-embolism. To
      evaluate the possibility of hypercoagulation in acute mesenteric ischemia (AMI);
      clinical features, ECG changes, drug history, the length of intestine remaining
      after the resection and mortality of 15 consecutive patients were recorded and
      plasma levels of antithrombin III, Protein C and protein S were measured.
      Antihypertensive, antidiabetic and digitalis were the main drugs used by the
      patients. Atrial fibrillation was the main ECG finding (60%). AMI was attributed
      to thrombo-embolic phenomena because of atrial fibrillation in these patients.
      Levels of antithrombin III and protein S were lower in patients without atrial
      fibrillation compared to those with the condition (mean values 16.18 vs. 18.04
      and 87.33 vs. 94.22 respectively) but the difference was not statistically
      significant. Levels of Protein C were lower and the length of intestine remaining
      after resection was shorter in patients without, compared to those with, atrial
      fibrillation (mean values 77.00 vs. 88.66, and 52.5 cm vs. 86.11 cm
      respectively). The difference was statistically significant (p < 0.05).
      Postoperative mortality rate was 33.3% (5 patients) and the length of intestine
      remaining after resection was the main determining factor in the prognosis of the
      patients. We conclude that a condition of hypercoagulation due to a deficiency of
      protein C has a significant role in the pathogenesis of AMI especially in
      patients without atrial fibrillation.

PMID- 15154577
TI  - Psoas abscess: a rare complication of Crohn's disease.
AB  - Psoas abscess is a rare complication of Crohn's disease. METHODS AND MATERIALS:
      We evaluated the incidence of psoas abscess on 312 patients with Crohn's disease,
      seen at our institution between 1992-2001. RESULTS: We encountered three cases of
      psoas abscess (0.9%). One patient was managed with ileocolic resection and
      immediate anastomosis, while in two patients a percutaneous drainage was first
      performed and then, after 12 days of total parenteral nutrition, a resection of
      the diseased bowel with immediate reconstruction was carried out. CONCLUSIONS: A
      correction of the nutritional deficiencies is mandatory. Percutaneous computed
      tomography guided drainage of the abscess with intestinal resection with
      immediate anastomosis, performed after a parenteral hyperalimentation, should be
      the method of choice in the management of such patients.

PMID- 15154578
TI  - Functional results after operative treatment of olecranon fractures.
AB  - In a retrospective, nonrandomized study, we reviewed our experience with the
      operative treatment of olecranon fractures to find out which factors correlate
      with subjective complaints and functional outcome. A total of 95 consecutive
      olecranon fractures were operatively treated in our level I trauma institution
      between March 1, 1992 and March 1, 2000. Medical charts and radiographs of all
      patients were evaluated. Three patients died, 23 were lost to follow-up. Fifty
      eight of 69 available patients (84.0%) were reviewed clinically and/or
      radiologically after a mean time interval of 36 months. Fracture type, fracture
      classification, associated lesions, technical correctness of osteosynthesis, age
      and comorbidity were analysed. Radiological end result (intraarticular step-offs,
      gaps, arthrosis), subjective complaints, mobility of the elbow joint and muscle
      strength were evaluated. Patients with an unstable elbow (Mayo classification
      type III and Schatzker-Schmeling classification type D) had a higher loss of
      elbow function than others. There was a correlation between fracture morphology
      (fractures type C and D in the Schatzker-Schmeling classification) and arthrosis.
      There also was a correlation between suboptimal osteosynthesis and arthrosis.
      There was no correlation between suboptimal osteosynthesis, implant loosening and
      secondary procedures. Patients more often expressed subjective complaints and
      loss of function in activities of daily life before than after hardware removal.
      Primary elbow instability and fracture morphology are prognostic factors for
      elbow function and development of arthrosis after operative treatment of
      olecranon fractures. We therefore recommend the classification systems of the
      Mayo-clinic or of Schatzker-Schmeling. As many patients have complaints related
      to the implants, we recommend hardware removal after fracture healing.

PMID- 15154579
TI  - Does octreotide impair anastomotic healing after small bowel resection?
AB  - Seventy two rats underwent small bowel resection followed by end-to-end
      anastomosis. The octreotide group consisted of 36 rats treated with octreotide
      (subcutaneously, 7 microg/kg/day, in two equal doses), and the control group
      consisted of 36 rats treated with the same volume saline. Twelve animals from
      each group were re-explored on the 4th, 8th and 15th postoperative day. Leakages,
      adhesions, obstructions were the clinical postoperative findings identified and
      recorded. Anastomotic bursting pressures were measured. Histochemical studies
      included haematoxylin-eosin and Van Gieson staining techniques and focused on the
      microscopic characterization of the healing process. Adhesions, leakages and
      obstructions were not different between octreotide and control groups.
      Anastomoses of the octreotide group had increased bursting pressures on the 8th
      and the 15th day (p < .05 , p < .05, respectively). Regarding the histogical
      results, on the 8th day the octreotide group compared to the control group,
      showed healing in more layers (p < .05), increased bright red collagen fibers and
      quantity of fibroblasts (p < .05), and on the 15th day, the octreotide group
      showed fewer gaps (p < .05), increased bright red collagen fibers and quantity of
      fibroblasts (p < .05). In this experimental model, it appeared that octreotide
      does not impair healing of small bowel anastomoses, but in contrast, there is
      some evidence that it enhances healing on the 8th and the 15th postoperative day.

PMID- 15154580
TI  - Spontaneous tracheal rupture: a case report.
AB  - We report the case of a spontaneous posterior tracheal wall rupture following a
      cough. A 67-year-old woman with a history of longstanding treatment with
      corticosteroids (8 years) for Giant Cell Arteritis had general anesthesia for
      cataract removal. Surgery and anesthesia were uneventful. In the recovery room,
      the patient coughed and soon after developed subcutaneous emphysema of the neck.
      Chest radiography confirmed the clinical diagnosis of marked subcutaneous
      emphysema and showed huge pneumomediastinum and minor right pneumothorax. A
      thoracic CT scan revealed a large laceration of the posterior tracheal wall (a 4
      cm longitudinal tear), extending from the middle of the trachea to the level of
      the carina. Surgical repair consisted in closure of the dilaceration using an
      autologous pericardial patch. It seems reasonable to suspect the facilitating
      role of connective tissue fragility due to chronic corticosteroid administration
      in the development of this tracheal rupture following cough. Tracheal rupture is
      a potentially lethal injury, which can be repaired successfully if the diagnosis
      is made early. Risk factors, diagnosis and principles of treatment of this lesion
      are discussed.

PMID- 15154581
TI  - Spermatocele: a rare complication of rectal surgery and radiotherapy. Case
      report.
AB  - A 47-year-old man developed a presacral mass after abdominoperineal resection,
      which is combined with pre and postoperative radio-chemotherapy for carcinoma of
      the rectum. CT-guided biopsy and cytological examination of the mass revealed no
      malignancy but spermatocele, which is a very unusual complication of rectal
      surgery.

PMID- 15154582
TI  - Surgical treatment of patent omphalomesenteric duct presenting as faecal
      umbilical discharge.
AB  - A newborn infant with patent omphalomesenteric duct (POMD), who presented faecal
      umbilical discharge, was treated with a semicircular periumbilical incision up to
      the abdominal cavity. The omphalomesenteric duct was followed up to the junction
      with the small intestine and there resected. The abdominal wall was closed
      without resection of the umbilicus.

PMID- 15154583
TI  - Isolated spleen metastatic involvement from a colorectal adenocarcinoma
      complicated with a gastrosplenic fistula. A case report and literature review.
AB  - We present the case of a 66-year-old man with a moderately differentiated
      adenocarcinoma of the left colon and isolated spleen metastases, complicated with
      a gastrosplenic fistula. The patient underwent a palliative segmental resection
      of the primitive colic tumour, as no curative treatment could be offered in view
      of the spleen involvement. Adjuvant chemotherapy was started. After a few
      chemotherapy treatments, he developed a gastrosplenic fistula which required the
      resection of the spleen and the greater gastric curvature together. This fistula
      was, among other things, responsible for bad breath that immediately disappeared
      postoperatively. At the end of the chemotherapy course, all carcinologic features
      had also disappeared.

PMID- 15154584
TI  - Epitheloid angiosarcoma of the splenic capsula as a result of foreign body
      tumorigenesis. A case report.
AB  - A case of an epitheloid angiosarcoma of the splenic capsula is reported. This
      tumour developed in close relation to a gauze sponge, which was accidentally left
      behind 38 years earlier during a left-sided nephrectomy. The tumour probably
      arose from pluripotential mesothelial stem cells within the splenic capsula, with
      subsequent mesothelial to endothelial metaplasia and neoplastic transformation.
      Clinical, radiological, peroperative and pathological features of this
      angiosarcoma add to the validity of the concept of inert foreign body
      tumorigenesis.

PMID- 15154585
TI  - Torsion of a wandering spleen presenting with acute abdomen: a case report.
AB  - Wandering spleen is a rare condition characterized by increased splenic mobility
      due to the absence or laxity of its suspensory ligaments that may present as
      acute abdomen when it is twisted on its pedicle. Herein we report a case of
      torsion of a wandering spleen in a 17-year-old male patient with communicating
      hidrocephalus and ventriculoperitoneal shunt. The patient presented with
      suspicious clinical findings of acute abdomen, a laparotomy was performed and the
      infarcted spleen was removed. Although wandering spleen is a rare clinical
      entity, the possibility of torsion should be kept in mind in the differential
      diagnosis of acute abdomen.

PMID- 15154586
TI  - Giant adrenal hemangioma: a case report.
AB  - Although adrenal masses are relatively common, hemangiomas occurring in adrenal
      glands are rare. This entity creates problems in the differential diagnosis. We
      report a patient with a giant cavernous hemangioma with a diameter of 13 cm,
      which was pre-operatively diagnosed as an adenoma or a malignant tumour. Clues to
      the correct diagnosis and therapeutic alternatives are discussed in the context
      of the available literature.

PMID- 15154587
TI  - Haemorrhagic shock from the spontaneous rupture of an adrenal cortical carcinoma.
      A case report.
AB  - Adrenal cortical carcinoma is a rare endocrine neoplasm which can be either
      functioning or non-functioning. Usually, patients refer to the doctor because of
      abdominal pain or symptoms associated with the mass effect. We present an unusual
      case of a patient with adrenal cortical carcinoma who was immediately operated
      due to massive retroperitoneal haemorrhage following the spontaneous rupture of
      the tumour. Adrenal cortical carcinoma should enter in differential diagnosis of
      retroperitoneal haemorrhage. Surgeons should be familiar with this clinical
      entity and attempt complete resection if possible.

PMID- 15154589
TI  - Ascending aorta syphilitic aneurysm presenting as a dystrophic disease.
AB  - A 37-year-old female originating from Central Africa presented with cardiac
      failure, aortic insufficiency and aortic root dilatation of supposed dystrophic
      origin. Left coronary ostial dilatation and dense adhesions between the aorta and
      the pulmonary trunk at operation were the only unusual features. However,
      pathological examination evoked a syphilitic disease and serology confirmed
      luetic infection. The diagnosis and the therapeutic approach are discussed.
      Syphilitic aneurysms belong to the protohistory of vascular surgery, but, in the
      antibiotherapy era, tracking a syphilitic aneurysm is like fishing for
      coelacanth. When this pathology mimics a dystrophic aneurysm, diagnosis and
      therapeutic attitude becomes hazardous and justifies the present report.

PMID- 15154588
TI  - Unusual presentation of renal cell carcinoma metastasis.
AB  - The aim of this study is to present an unusual site of renal cell carcinoma
      metastasis. A 60-year old man presented to our clinic with massive rectal
      bleeding. A large small intestine metastasis from renal cell carcinoma was
      evidenced by an elective angiography of the superior mesenteric artery. This
      metastasis was surgically excised.

PMID- 15154590
TI  - Hyperfunctioning parathyroid cysts: a case report.
AB  - Parathyroid cysts are infrequent lesions of which most are non-functional. They
      are often misdiagnosed as thyroid cysts. Pre-operative diagnosis and
      differentiation from thyroid cysts is generally difficult. We hereby report a
      case that was admitted to the emergency room and was diagnosed as hypercalcemic
      crisis. The mass found during the neck examination was thought to be a thyroid
      nodule. A right total and left subtotal thyroidectomy was performed. Palpable
      thyroid nodule was diagnosed as cystic parathyroid adenoma postoperatively. When
      a cystic lesion is found in the neck of a patient, a pararthyroid cyst should be
      considered.

PMID- 15154591
TI  - Treatment of a metastasis of a rectal carcinoma in the greater trochanter with
      the AO/ASIF Proximal Femoral Nail. A case report.
AB  - A 48-year-old patient was referred to our department because of a solitary
      metastasis of a rectal carcinoma, localized in the left greater trochanter. Since
      the risk of pathological fracture was higher than acceptable for radiation
      therapy alone and because of the young age of the patient, radical debulking and
      reconstruction using the AO/ASIF Proximal Femoral Nail and cement augmentation
      was performed. Solitary bone metastases of colorectal adenocarcinomata are rare,
      as discussed. The prognosis of a primary colorectal carcinoma in the presence of
      a bone metastasis, even a solitary one, is poor. In patients with these
      metastases with poor overall prognosis, the treatment objectives, which we could
      define as 'safe, short and simple' are stringent, although there most certainly
      remains an indication for palliative surgery.

PMID- 15154592
TI  - Concerns "Sleeve lobectomy for non-small cell lung cancer". P. De Leyn, W. Rots,
      G. Deneffe, Acta Chir Belg, 2003, 103, 570-576.

PMID- 15154593
TI  - Isolation and selection of ionophore-tolerant Eimeria precocious lines: E.
      tenella, E. maxima and E. acervulina.
AB  - Eimeria parasites were isolated from Nanhai Guangdong province (southern China)
      and studied in chickens in wire cages to evaluate their drug resistance against
      commonly used ionophores: monensin (100 mg/kg of feed), lasolacid (90 mg/kg),
      salinomycin (60 mg/kg), maduramicin (5 mg/kg) and semduramicin (25 mg/kg).
      Chinese Yellow Broiler Chickens were infected with 40,000 crude sporulated
      Eimeria oocysts at 15 days of age and prophylactic medication commenced a day
      prior to infection. Drug resistance was assessed for each ionophore drug by
      calculating the anticoccidial index (ACI) and percentage optimum anticoccidial
      activity (POAA) based on relative weight gain, rate of oocyst production and
      lesion values. Results revealed that Nanhai Eimeria oocysts comprising of E.
      tenella, E. maxima and E. acervulina, were resistant to monensin, sensitive to
      both salinomycin and lasolacid and partially sensitive to maduramicin and
      semduramicin. By selection for early development of oocysts during passage
      through chickens, the prepatent time of E. tenella, E. maxima and E. acervulina
      were reduced by 49, 36 and 22 h, respectively. The precocious lines are less
      pathogenic than the parent strains from which they were selected and conferred a
      satisfactory protection for chickens against coccidiosis. These ionophore
      tolerant precocious lines could have wider applications in the development of
      anticoccidial vaccines for sustainable control of coccidiosis.

PMID- 15154594
TI  - Morphological identification of nematode larvae of small ruminants and cattle
      simplified.
AB  - A simplified system has been developed to facilitate identification of nematode
      larvae of the common nematodes of cattle, sheep and goats. Firstly, in addition
      to the characteristics conventionally used for identification (such as the shape
      of the cranial extremity and numbers of intestinal cells), the lengths of the
      infective sheath tails of infective larvae of each genus/species are related to
      that of Trichostrongylus spp. instead of using measurements for differentiation.
      For instance, if the mean length of the sheath tail (the distance the sheath
      extends caudad beyond the caudal tip of the larva) of Trichostrongylus spp. is
      assumed to be "X", then that of Haemonchus contortus is 2-2.7"X", and that of
      Oesophagostomum spp. from sheep is 4-7"X", etc. Secondly, by estimating the
      proportion of the sheath tail of a larva comprised of a terminal thin whip-like
      filament, identification is aided, particularly in those L3 of species that
      resemble one another closely, such as Chabertia ovina and Oesophagostomum
      venulosum or Oesophagostomum columbianum. After some practice with the system it
      is usually necessary to measure only one or two sheath tails of L3 in a mixed
      population, whereupon the identity of most of the remaining L3 can be estimated
      in relation to those measured, without a need for further measurements. The keys
      were found to facilitate differential larval identification and are particularly
      useful for training.

PMID- 15154595
TI  - Seasonal development of Cyathostominae larvae on pasture in a northern temperate
      region of the United Kingdom.
AB  - A study following the development of Cyathostominae from egg to the infective
      larval third stage was conducted from April to December 2001 in west central
      Scotland. Duplicate samples (1 kg) of naturally infected faeces were placed on a
      78 cm2 plot each week on a cyathostomin-free pasture. Subsamples of the grass
      surrounding the faecal plot were collected weekly on four occasions and the
      number of larvae obtained determined. Few larvae were recovered in the first week
      of development of individual plots, followed by a rise in the numbers of larvae
      in second, third and fourth weeks of development of each sample. The climatic
      conditions were seen to have an effect on the rate of development. Specifically,
      from multilevel, multivariable linear regression models it was evident that the
      factors associated with numbers of infective larvae recovered from pasture were
      the time since the faeces samples were laid down, the average temperature and
      rainfall during the previous week, as well as the interaction between temperature
      and rainfall. Conversely, from the model, the number of larvae recovered from
      pasture was associated with neither the number of eggs within the faeces samples
      placed on the plots nor with the viability of these eggs.

PMID- 15154596
TI  - Prevalence of Dirofilaria immitis and gastrointestinal helminths in cats
      euthanized at animal control agencies in northwest Georgia.
AB  - Cats euthanized at six northwest Georgia animal control agencies were examined
      for adult Dirofilaria immitis in heart and lung tissue and presence of
      gastrointestinal helminth ova by fecal flotation. D. immitis were found in 4 of
      184 cats (2.1%). The prevalence of feline dirofilariasis in northwest Georgia was
      lower than that found in other studies conducted in the southeastern United
      States, but closer to the prevalences occurring in areas of similar topography.
      Heartworm antigen and antibody tests performed on batched serum samples resulted
      in low sensitivity and high specificity. Gastrointestinal helminth ova were found
      in 39.6% of the fecal samples examined and 6.1% of the samples contained two or
      more species.

PMID- 15154597
TI  - Entamoeba struthionis n.sp. (Sarcomastigophora: Endamoebidae) from ostriches
      (Struthio camelus).
AB  - In the present work we identify the species of Entamoeba from ostriches (Struthio
      camelus). The complete sequence of the small subunit ribosomal RNA gene from this
      organism has been compared with those published for other species of the genus
      and clear differences have been found. These results confirm previous data which
      showed differences on parasite morphology and class of host with the other
      Entamoeba species. Taking all these data together, it can be concluded that the
      organism from ostriches is a new species whose proposed name is Entamoeba
      struthionis n.sp. This species probably infects rheas (Rhea americana), but
      genetic analysis of isolates from this host should be performed to confirm
      morphological data. Also, comparison of gene sequences with data from other
      authors on cysts recovered from human stool samples showed the possibility that
      this amoeba may affect humans. Further studies are needed to determine the risk
      of transmission of this new species to humans.

PMID- 15154598
TI  - The "expanding universe" of piroplasms.
AB  - The present paper is the continuation of our previous studies dealing with the
      genetic characterization of piroplasmid species found in southern Europe. We
      report in this work new data concerning sequences of the 18s rRNA gene in Spanish
      piroplasms not studied (or not totally sequenced) in our former surveys.
      Molecular data analysis indicated that Spanish Cytauxzoon felis (cat isolate) has
      98% identity with Cytauxzoon sp. from Mongolia and 95% identity compared to
      African C. felis. There are at least two main genetic variants of Babesia caballi
      in Spain: The first variety (isolate Spain 1) shows a relatively low homology
      with the African genotype (97% identity). The second variety (represented by two
      isolates, Spain 2 and Spain 3, differing by a single base) shows high genetic
      similarity with the African genotype (99.7-100% identity). There are also two
      genetic variants of Babesia equi (isolates Spain 1 and Spain 2, differing by four
      bases) in Spain, sharing 99% identity with the African genotype. At least one of
      them (Spain 1) can infect dogs. All of the phylogenetic analysis procedures
      employed indicated that Spanish isolates of C. felis, B. caballi (Spain 1) and B.
      equi (Spain 1 and Spain 2) are genetically different from their African
      relatives, all those dichotomies showing very high bootstrap support.
      Nonetheless, the lack of information on their morphology and the fact that the
      sequences were obtained in a single isolate preclude any conclusion about their
      definitive taxonomic status.

PMID- 15154599
TI  - Pathophysiology and treatment of platelet-mediated microvascular disturbances,
      major thrombosis and bleeding complications in essential thrombocythaemia and
      polycythaemia vera.
AB  - Essential thrombocythaemia (ET) is associated with a broad spectrum of
      microvascular circulation disturbances including erythromelalgia and its
      ischaemic complications, episodic neurological symptoms of atypical and typical
      transient ischaemic attacks (TIAs), transient ocular ischaemic attacks, acute
      coronary syndromes, and superficial 'thrombophlebitis'. The microvascular
      circulation disturbances are caused by spontaneous activation and aggregation of
      hypersensitive thrombocythaemic platelets at high shear stress in the endarterial
      microcirculation involving the peripheral, cerebral and coronary circulation. As
      this microvascular syndrome is a pathognomonic feature of essential
      thrombocythaemia and of thrombocythaemia associated with polycythaemia vera (PV)
      in complete remission with normal haematocrit, we have labelled these two
      variants of thrombocythaemia as thrombocythaemia vera. The arterial thrombophilia
      of microvascular circulation disturbances in thrombocythaemia vera already occur
      at platelet counts in excess of 400 x 10(9)/l. Complete relief of microvascular
      circulation disturbances in thrombocythaemia vera is obtained with the platelet
      cyclooxygenase inhibitor aspirin 50-100 mg/day, but not with dipyridamole,
      ticlopidine, coumarin or heparin. Haemorrhagic thrombocythaemia (HT) is a
      clinical syndrome of recurrent spontaneous mucocutaneous and secondary
      haemorrhages associated with extremely high platelet counts far in excess of 1000
      x 10(9)/l. The paradoxical occurrence of microvascular circulation disturbances
      and mucocutaneous bleeding is usually seen at platelet counts between 1000 and
      2000 x 10(9)/l. At increasing platelet counts from below 1000 to in excess of
      2000 x 10(9)/l, the arterial thrombophilia of thrombocythaemia vera changes into
      a spontaneous bleeding tendency of HT as a consequence of platelet-mediated
      increased proteolysis of the large von Willebrand factor multimers leading to a
      type 2 acquired von Willebrand syndrome. As PV is usually associated with
      thrombocythaemia, the vascular complications in PV patients are microvascular
      circulation disturbances typical of thrombocythaemia. On top of this, major
      arterial and venous thrombotic events and haemorrhages are related to increased
      haematocrit, red cell mass and its concomitant increased blood viscosity.
      Correction of increased blood viscosity and haematocrit to normal values (0.40
      0.44) by bloodletting alone will significantly reduce the risk of major
      thrombotic complications, but does not prevent the microvascular circulation
      disturbances because thrombocythaemia persists. The microvascular syndrome
      associated with thrombocythaemia in PV patients in remission after bloodletting
      is best controlled by low-dose aspirin (50-100 mg/day) or by reduction of
      platelet count to normal (< 350 x 10(9)/l).

PMID- 15154600
TI  - Quantitation of platelet aggregation and microaggregate formation in whole blood
      by flow cytometry.
AB  - Platelet aggregation and microaggregate formation were measured in samples of
      stirred whole blood by flow cytometry. Blood samples were stirred in a multi
      sample agitator with ADP, fixed and labelled with a platelet-specific CD42a-FITC
      fluorescent antibody. The blood was then diluted and applied directly to a flow
      cytometer. Platelets were identified using a gating procedure based on their
      expression of CD42a and then quantified. Aggregation was monitored as a fall in
      the number of single platelets. Both reversible and irreversible aggregation
      responses to ADP were determined and these were found to correlate directly with
      aggregation responses determined using a well-established single platelet
      counting technique using the Ultra-Flo 100 Whole Blood Platelet Counter. We found
      from flow cytometry that ADP-induced aggregation was coupled with a transient
      formation of platelet microaggregates over the initial 60 s following ADP
      addition. Assessment of single platelet loss by flow cytometry was found to be a
      reliable way of monitoring aggregation responses and provided new information on
      rapid microaggregate formation in ADP-stimulated blood.

PMID- 15154601
TI  - Failure of clopidogrel to reduce platelet reactivity and activation following
      standard dosing in elective stenting: implications for thrombotic events and
      restenosis.
AB  - There is no information on long-term platelet reactivity and activation following
      elective stenting in patients treated with clopidogrel and aspirin. We measured
      platelet reactivity and activation at baseline and at 2 h, 24 h, 5 days and 30
      days following coronary stenting (n = 94). Patients were treated with the
      standard aspirin (325 mg) and clopidogrel regimen (300 mg load/75 mg qd).
      Reactivity was measured by aggregation (5 and 20 microM ADP) and activation was
      determined by the expression of total and active GP IIb/IIIa. Reactivity and
      activation were defined as heightened when post-stent aggregation and receptor
      expression exceeded baseline levels, respectively. Prolonged heightened platelet
      reactivity was detected by both 5 and 20 microM ADP aggregation. Using 20 microM
      ADP aggregation, heightened reactivity occurred in 55% of patients at 2 h, 26% at
      24 h, 21% at 5 days, and 15% at 30 days post-stenting. A high frequency of
      heightened platelet activation was detected by both total and active GP IIb/IIIa
      expression. Using expression of the active GP IIb/IIIa receptor as the marker,
      activation was greater than baseline in 27% of patients at 2 h, 20% at 24 h, 30%
      at 5 days, and 22% at 30 days post-stenting. This is the first report
      demonstrating that a significant percentage of patients receiving standard
      clopidogrel and aspirin therapy for coronary stenting will have post-drug
      platelet reactivity and activation above baseline that persists for 30 days after
      the procedure. These finding suggest insufficient platelet inhibition. The
      clinical importance of these findings should be further investigated to establish
      the potential link between insufficient platelet inhibition, stent thrombosis,
      and restenosis.

PMID- 15154602
TI  - Platelet activity, reactivity and platelet-leukocyte conjugate formation before
      and after exhaustive or moderate exercise in patients with IDDM.
AB  - Diabetes mellitus alters blood coagulation and platelet function which supports
      the suggestion that diabetes mellitus is a hypercoagulable state. Firstly the aim
      of the study was to investigate if differences in platelet activity, reactivity
      and platelet-leukocyte conjugate (PLC) formation can be observed in subjects with
      IDDM; secondly, if differences can be seen between the diabetic and control group
      concerning exercise-induced changes in platelet activation and conjugate
      formation; and thirdly, if different types of exercise lead to different patterns
      in platelet activation. Sixteen subjects with IDDM and 16 controls underwent a
      maximal step test and an endurance test (90% IAT, 45 min). Blood samples were
      taken after 30 min rest, and immediately and 1 h after completion of exercise.
      CD62P expression and differentiated platelet-leukocyte conjugates (CD45, CD14,
      CD41) were detected flow-cytometrically with and without stimulation with TRAP-6.
      The rest values of the platelet-granulocyte (PGC) and platelet-lymphocyte
      conjugates (PLyC) were higher (P < 0.05) in the diabetics. After exercise,
      platelet reactivity (CD62P-TRAP; P < 0.05) but not the activity (CD62P
      unstimulated), as well as all different conjugates with or without stimulation
      were increased (P < 0.05) independently from the group. Differences according to
      the type of exercise were barely observable. IDDM without vascular complications
      leads to higher PCG and PLyC at rest and to identical increases in differentiated
      platelet-leukocyte formation after exercise in comparison with matched controls.

PMID- 15154603
TI  - Platelet-derived microvesicles transfer tissue factor to monocytes but not to
      neutrophils.
AB  - Activated platelets are known to adhere to both blood monocytes and neutrophils,
      and this adhesion is mainly mediated by the surface exposure of the platelet
      granule protein CD62P. Platelets as well as platelet-derived microvesicles (PMV)
      have also been shown to contain and to transfer tissue factor (TF), the most
      important initiator of intravascular thrombin and fibrin formation, to monocytes.
      However, the role of neutrophils for gathering platelet-derived TF is
      controversial. Here we studied the interaction of PMV with monocytes and
      neutrophils using a whole blood system. Platelet-rich plasma (PRP) obtained from
      citrated human blood was incubated with collagen (5 microg/ml, 15 min) and the
      platelets were removed by centrifugation (5 min at 5000 x g). After incubating
      the PMV-containing plasma for further 30 min with a sediment of red and white
      bloods cells that had been obtained after PRP preparation, monocytes and
      neutrophils were analysed by flow cytometry for the surface exposure of the
      platelet-specific antigen CD42a and TF. Compared to a control with non-activated
      PRP, there was a significant increase in the number of both CD42a-positive
      monocytes and neutrophils. In contrast, there was no change in the number of TF
      positive neutrophils, but a more than 2-fold increase in the number of TF
      positive monocytes. The changes in CD42a on monocytes and neutrophils as well as
      the changes in TF on monocytes could be significantly reduced by an anti-CD62P
      antibody or by removal of PMV from the plasma samples. The data indicate that the
      transfer of TF to monocytes is not simply an CD62P-mediated adhesion of platelets
      or PMV to monocytes, but may involve other not yet identified mechanisms.

PMID- 15154604
TI  - The effect of clopidogrel, aspirin and both antiplatelet drugs on platelet
      function in patients with peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is associated with platelet hyperactivity.
      Aspirin and clopidogrel, two platelet inhibitors, act by different mechanisms.
      Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12
      platelet ADP receptor. We evaluated the effect of clopidogrel (75 mg/day),
      aspirin (75 mg/day) and then both drugs on several platelet function indices in
      patients with PAD (n = 20). There was a significant (P = 0.0001) decrease in ADP
      induced aggregation, after clopidogrel but not after taking aspirin. Clopidogrel
      plus aspirin significantly decreased spontaneous platelet aggregation (SPA) (P =
      0.01 to P = 0.002) but SPA was not significantly altered by either aspirin or
      clopidogrel monotherapy. Similarly, monotherapy did not inhibit serotonin (5HT)
      induced aggregation but there was a sigificant inhibition (P = 0.03 to P < 0.02)
      after combination therapy. ADP (0.8 microM)-induced platelet shape change (PSC)
      was significantly inhibited by clopidogrel (P = 0.004) or aspirin (P = 0.01).
      This was also true for 5HT-induced PSC (clopidogrel, P = 0.01; aspirin, P =
      0.03). Soluble P-selectin decreased significantly (from 32 +/- 24 to 25 +/- 17
      ng/ml, P = 0.04) with combination therapy. Plasma platelet-derived growth factor
      and intraplatelet 5HT levels were not altered by combination therapy. In PAD,
      clopidogrel is a more potent inhibitor of ADP-induced platelet activation than
      aspirin; combination therapy is more effective than clopidogrel or aspirin
      monotherapy. These potentially clinically relevant findings should be evaluated
      in appropriately designed trials.

PMID- 15154606
TI  - Testing for antiphospholipid antibody (aPL) specificities in retrospective
      "normal" cerebral spinal fluid (CSF).
AB  - Antiphospholipid antibodies (aPL) have been found in the blood of patients with
      systemic and neurological disease. The rare reports of aPL in cerebral spinal
      fluid (CSF) have been limited mostly to IgG and IgM anticardiolipin (aCL). Our
      published finding of IgA aPE in the CSF of a young stroke victim prompted us to
      establish "normal" CSF aPL values for a panel of aPL, which included aCL,
      antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE) and
      antiphosphatidylcholine (aPC). CSF samples were tested by ELISA for IgG, IgM and
      IgA aPL. In addition, the CSF samples were tested for activity in the presence
      and absence of phospholipid (PL) binding plasma-proteins. A total of 24 data
      points were obtained for each CSF sample. We tested 59 CSF samples obtained from
      59 patients who were undergoing evaluation for systemic or neurologic diseases.
      All CSF samples had normal protein, glucose and cell counts. Ten of the 59 CSF
      samples (17%) had elevated aPL optical density (OD) values an order of magnitude
      higher than the other 49 CSF samples for one or more aPL specificity and/or
      isotype. One CSF sample had both PL-binding protein dependent and independent IgG
      aPE activity. Another CSF sample showed both IgG aPE and aPC reactivity. The
      remaining eight CSF samples showed single aPL findings; IgG aPE (5), IgG aPC (1),
      IgG aCL (1) and IgM aPC (1). Seven of 10 patients with elevated CSF values were
      females. As expected, most "normal" aPL OD values were substantially lower in CSF
      than those we have reported in blood samples from volunteer blood donors.

PMID- 15154605
TI  - Immunopathological basis of virus-induced myocarditis.
AB  - Heart diseases are an important cause of morbidity and mortality in
      industrialized countries. Dilated cardiomyopathy (DCM), one of the most common
      heart diseases, may be the consequence of infection-associated myocardits.
      Coxsackievirus B3 (CVB3) can be frequently detected in the inflamed heart muscle.
      CVB3-induced acute myocarditis is most likely the consequence of direct virus
      induced myocyte damage, whereas chronic CVB3 infection-associated heart disease
      is dominated by its immunopathological sequelae. Bona fide autoimmunity, for
      example, directed against cardiac myosin, may favor chronic destructive immune
      damage in the heart muscle and thereby promote the development of DCM. The
      immunopathogenesis of myocarditis and subsequent DCM induced either by pathogens
      or autoantigens can be investigated in well-established animal models. In this
      article, we review recent studies on the role of viruses, with particular
      emphasis on CVB3, and different immunological effector mechanisms in initiation
      and progression of myocarditis.

PMID- 15154607
TI  - Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from
      asthma patients on dietary supplementation with gammalinolenic acid-containing
      borage oil: possible implication in asthma.
AB  - Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX)
      and suppressor of leukotriene B4 (LTB4), can attenuate the clinical course of
      rheumatoid arthritics, with negligible side effects. Since Zileuton, also an
      inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we
      investigated whether dietary GLA would suppress biosynthesis of PMN-LTB4 isolated
      from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma
      patients (16-75 years) were randomized to receive either 2.0 g daily GLA (borage
      oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was
      used to prepare sera for fatty acid analysis, PMNs for determining phospholipid
      fatty acids and for LTB4 generation. Patients were monitored by daily asthma
      scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased
      DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15
      HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the
      decreased PMN generation of proinflammatory LTB4. However, the suppression of PMN
      LTB4 did not reveal statistically significant suppression of the asthma scores
      evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of
      endogenous inflammatory mediators without side effects and thus warrant further
      explorations into the roles of GLA at higher doses, leukotrienes and asthma.

PMID- 15154608
TI  - Identification of germinal center B cells in blood from HIV-infected drug-naive
      individuals in Central Africa.
AB  - To better understand the pathophysiology of B cell populations-the precursors of
      antibody secreting cells-during chronic human immunodeficiency virus (HIV)
      infection, we examined the phenotype of circulating B cells in newly diagnosed
      Africans. We found that all African individuals displayed low levels of naive B
      cells and of memory-type CD27+ B cells, and high levels of differentiated B
      cells. On the other hand, HIV-infected African patients had a population of
      germinal center B cells (i.e. CD20+, sIgM-, sIgD+, CD77+, CD138(+/-)), which are
      generally restricted to lymph nodes and do not circulate unless the lymph node
      architecture is altered. The first observations could be linked to the tropical
      environment whereas the presence of germinal center B cells may be attributable
      to chronic exposure to HIV as it is not observed in HIV-negative African controls
      and HAART treated HIV-infected Europeans. It may impact the management of HIV
      infection in countries with limited access to HIV drugs and urges consideration
      for implementation of therapeutic vaccines.

PMID- 15154609
TI  - Development of T lymphocytes in the nasal-associated lymphoid tissue (NALT) from
      growing Wistar rats.
AB  - The aim of the present report was to study the development of several T
      lymphocyte subsets in the nasal-associated lymphoid tissue (NALT) of growing
      Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A
      predominance of CD8alpha+ over CD4+ T cells was found from 7 to 45 days but from
      45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The
      majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most
      relevant findings by immunohistochemistry are: (1) the predominance of
      TCRgammadelta+ and CD8alpha+ cells at 7 days postpartum over all the other T-cell
      subpopulations; and (2) that TCRgammadelta+ outnumbered TCRalphabeta+ T cells
      from 7 to 45 days postpartum whereas alphabeta T cells predominated in 45- and 60
      day-old rats. Besides, cytometric studies have shown that the percentages of
      TCRgammadelta+, CD8alpha+, as well as the population coexpressing both phenotypes
      (TCRgammadelta+CD8alpha+), were significantly higher in rats at 7 days postpartum
      when compared to 60 day-old rats. In the present study, the finding of a high
      number of gammadelta+ and CD8+ T cells early in NALT development may indicate the
      importance of these subpopulations in the protection of the nasal mucosa in
      suckling and weaning Wistar rats.

PMID- 15154610
TI  - Genetic analysis of cytokine promoters in nonhuman primates: implications for
      Th1/Th2 profile characteristics and SIV disease pathogenesis.
AB  - The shift from a predominant synthesis of prototype Th1 cytokines to Th2 or Th0
      type of cytokines by antigen activated PBMC's from HIV infected humans and SIV
      infected disease susceptible rhesus macaques (RM) has been shown to be associated
      with disease progression. Paradoxically, antigen activated PBMC's from sooty
      mangabeys (SM), which are naturally infected with SIV and are disease resistant
      despite high viral loads, maintain a predominant Th2 cytokine profile. It has
      been reasoned that the resistance to perturbations of cytokine synthesis by slow
      and/or nonprogressor HIV infected patients and SIV infected disease susceptible
      RM is secondary to inherited polymorphisms within the promoter regions for
      cytokines. Similar promoter polymorphisms could also contribute to the cytokine
      profile of PBMC's from SM. To address this issue promoter regions for the major
      Th1/Th2 cytokines from RM and SM were cloned and sequenced. Sequence analysis of
      promoter fragments of IL-4, IL-10, IL-12 p40, IFN-gamma and TNF-alpha from the
      two monkey species showed varying degree of homology ranging from high degree of
      homology detected for IFN-gamma promoter (> 99%) to relatively high degree of
      polymorphism detected for TNF-alpha promoter (94% homology). In addition, several
      variable regions within the promoters of IL-12 p40, IL-10 and TNF-alpha in the
      two species contain polymorphisms in sequences that constitute binding sites of
      known transcription factors (TF). Such differences are likely to differentially
      bind TF and thus either qualitatively and/or quantitatively affect the regulation
      of cytokine synthesis in these two species and potentially contribute to disease
      progression and/or resistance.

PMID- 15154611
TI  - Neurohypophysial receptor gene expression by thymic T cell subsets and thymic T
      cell lymphoma cell lines.
AB  - Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in
      thymic epithelium, while immature T lymphocytes express functional
      neurohypophysial receptors. Neurohypophysial receptors belong to the G protein
      linked seven-transmembrane receptor superfamily and are encoded by four distinct
      genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the
      nature of neurohypophysial receptor in thymic T cell subsets purified by
      immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP
      and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines,
      while V3R transcription is restricted to CD4+CD8+ and CD8+ thymic cells. Neither
      V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was
      identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6
      mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not
      modify the percentage of T cell subsets, but increases late T cell apoptosis
      further evidencing the involvement of OT/OTR signaling in the control of T cell
      proliferation and survival. According to these data, OTR and V3R are
      differentially expressed during T cell ontogeny. Moreover, the restriction of OTR
      transcription to T cell lines derived from thymic lymphomas may be important in
      the context of T cell leukemia pathogenesis and treatment.

PMID- 15154612
TI  - Autoantibodies profile in the sera of patients with Sjogren's syndrome: the ANA
      evaluation--a homogeneous, multiplexed system.
AB  - BACKGROUND: Flow-based, multiplex bead arrays (MBA) have been developed for a
      variety of applications including the detection of antibodies to extractable
      nuclear antigens (ENA). It offers a rapid and sensitive method to assess multiple
      analyses in a single tube/well. PURPOSE: To evaluate the Athena Multi-Lyte ANA
      Test System utilizes Luminex Corporation's MBA technology for the detection of
      antinuclear antibodies (ANA) and ENA antibodies in the sera of patients with
      Sjogren's syndrome (SS). METHODS: MBA assay was used to detect ANA and ENA
      antibodies in the sera of 37 patients with SS and 96 sera from healthy subjects.
      RESULTS: All patients were women. Their mean age was 48.7 years and the mean
      disease duration was 7.27 years. ANA was found in 3 (3%) sera of healthy subjects
      by the AtheNA system and in 2 (2%) sera by the ELISA kit. A 99% concordance
      between the 2 assays was found. A 94.6% concordance between the 2 assays was
      found by testing the sera of patients with SS for ANA. By the AtheNA system, none
      of the sera of 37 patients with SS had autoantibodies reacting with Sm, Jo-1,
      dsDNA or histones. Anti-RNP antibody was found in 5.4% of the sera and 2.7% of
      the sera reacted with Scl-70 and histones. Anti-SS/A and anti-SS/B were
      identified in 84 and 76% of the sera, respectively. CONCLUSION: The AtheNa Multi
      Lyte ANA Test System offers a sensitive and specific result for the detection of
      ANA and ENA antibodies in the sera of patients with SS.

PMID- 15154613
TI  - A review of pityriasis rubra pilaris and rheumatologic associations.
AB  - Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous
      disease that can be acquired or inherited. There have been reported cases of
      rheumatologic associations, mainly arthritis and dermatomyositis. In this review
      article, we will explore the clinical presentation and classification,
      rheumatologic associations and treatment modalities of PRP. In addition, we will
      also report a case of PRP with seronegative arthritis.

PMID- 15154614
TI  - Circulating immune complexes among diabetic children.
AB  - Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease associated
      with the presence of different types of autoantibodies. The presence of these
      antibodies and the corresponding antigens in the circulation leads to the
      formation of circulating immune complexes (CIC). CIC are known to persist in the
      blood for long periods of time. Such CIC following deposition in the small blood
      vessels have the potential to lead to microangiopathy with debilitating clinical
      consequences. The aim of our pilot study was to investigate whether a correlation
      exists between CIC and the development of microvascular complications in diabetic
      children. Isolation of a new glycoprotein complement inhibition factor (CIF) from
      the parasitic plant Cuscuta europea seed, which appears to bind specifically to
      complement component C3 has provided an unique tool for the measurement of immune
      complexes by means of ELISA-type techniques (CIF-ELISA). We studied the levels of
      CIC (IgG, IgM and IgA) in 58 diabetic children (mean age 12.28 +/- 4.04 years,
      diabetes duration 5.3 +/- 3.7 years), 29 of them had vascular complications
      (group 1) and the other 29 were without vascular complications (group 2). As
      controls, we studied sera samples from 21 healthy children (mean age 13.54 +/-
      4.03 years). Sera from the diabetic patients showed statistically significant
      higher levels of CIC IgG (p = 0.03) than sera from the control group. In sera
      from group 1 values of CIC IgG showed statistically significant higher levels
      than controls (0.720 +/- 0.31 vs. 0.46 +/- 0.045; p = 0.011) Sera from 59% of the
      patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26
      patients with microalbuminuria, sera from 17/26 (65%) were positive for CIC IgG,
      8/26 (31%) for CIC IgM and 2/26 (8%) for CIC IgA. CIC IgG correlated with HbAlc
      (r = 0.51; p = 0.005) and microalbuminuria (r = 0.42, p = 0.033). CIC IgA
      correlated with age (r = 0.44, p = 0.03). CIC IgM correlated with the duration of
      diabetes (r = 0.63, p = 0.02). These findings suggest that elevated levels of CIC
      IgG are associated with the development of early diabetic nephropathy.

PMID- 15154615
TI  - Neurological dysfunction associated with antiphospholipid syndrome:
      histopathological brain findings of thrombotic changes in a mouse model.
AB  - The aim of this work was to study the pathological processes underlying
      neurological dysfunctions displayed by BALB/C mice induced with experimental
      antiphospholipid syndrome (APS), as we have previously reported. Experimental APS
      was induced in female BALB/C mice by immunization with a pathogenic monoclonal
      anticardiolipin (aCL) antibody, H-3 (n = 10), or an irrelevant immunoglobulin in
      controls (n = 10). Mice immunized with H-3 developed clinical and neurological
      manifestations of APS, including: embryo resorption, thrombocytopenia
      neurological defects and behavioral disturbances. In mouse sera, the titer of
      various autoantibodies were elevated, including: anti-phospholipids (aPLs), anti
      beta2 glycoprotein-I (beta2GPI), anti-endothelial cell antibodies (AECA) and low
      titer of anti-dsDNA antibodies. Five months after APS induction, mice were
      sacrificed and brain tissue specimens were processed for hematoxylin and eosin
      (H&E), immunofluorescence staining and transmission electron microscopy (TEM).
      H&E staining of cortical tissue derived from all APS mice revealed mild
      inflammation, localized mainly in the meninges. Prominent IgG deposits in the
      large vessel walls and perivascular IgG leakage were observed by
      immunofluorescence. No large thrombi were observed in large vessels. However, EM
      evaluation of cerebral tissue revealed pathological changes in the microvessels.
      Thrombotic occlusion of capillaries in combination with mild inflammation was the
      main finding and may underlie the neurological defects displayed by mice with
      APS.

PMID- 15154616
TI  - Identification of the molecular mechanism by which TLR ligation and IFN-gamma
      synergize to induce MIG.
AB  - Monokine Induced by Interferon-gamma (MIG), a CXC chemokine, is a potent inducer
      of T-cell chemotaxis and activation and has been implicated in the host response
      to viral infections and tumor immunity as well as in the pathogenesis of
      autoimmunity and transplant rejection. Although it is known that the Toll-Like
      Receptor-4 (TLR-4) ligand LPS synergizes with IFN-gamma to induce MIG expression
      in macrophages, the molecular mechanisms responsible for the synergy have yet to
      be elucidated. We determined that the marked synergy between LPS and IFN-gamma on
      MIG mRNA expression in mouse macrophages is a result of LPS-induced NF-kappaB and
      IFN-gamma-induced STAT. The synergy was not dependent on new protein synthesis,
      was independent of TNF-alpha, and occurred at the level of gene transcription. We
      identified 2 NF-kappaB sites located at -154 and -129 of the MIG promoter
      proximal to the gamma-responsive element that mediated this effect. Finally, we
      demonstrated that other TLR ligands (zymosan, double stranded RNA and CpG)
      synergized with IFN-gamma to induce MIG in an NF-kappaB dependent fashion. These
      data emphasize the ability of bacterial and viral products to activate/modify
      immune responses and promote adaptive T cell immunity through the NF-kappaB
      pathway.

PMID- 15154617
TI  - Relationship between pollen counts and weather variables in east-Mediterranean
      coast of Turkey. Does it affect allergic symptoms in pollen allergic children?
AB  - BACKGROUND: Aeroallergen sampling provides information regarding the onset,
      duration and severity of the pollen season that clinicians use to guide allergen
      selection for skin testing and treatment. OBJECTIVES: This atmospheric survey
      reports (1) airborne pollen contributions in Adana in one-year period (2) pollen
      onset, duration and peak level (3) the relationship between airborne pollen and
      selected meteorological variables and; (4) effects on symptoms in pollen allergic
      children. METHODS: Pollen sampling was performed with a volumetric Burkard Spore
      Trap. Meteorological data were measured daily from April 2001 to April 2002.
      Asthma symptom scores were investigated in 186 pollen allergic children that were
      on follow up in pediatric allergy outpatient clinics during same period. RESULTS:
      Average measurements included 82.5% tree pollen, 7.7% grass pollen and 9.8% herb
      pollen 54 taxa were identified during one year. The most prominent tree pollens
      were Cupressaceae, Eucalyptus and Pinus. The most common herb was Chenopodiaceae
      pollen family. When airborne pollen levels were examined in relation to single
      meteorological conditions; daily variations in total pollen counts were not
      significantly correlated with any variable studied (humidity, rainfall,
      temperature and wind) (p > 0.05). On the other hand, statistically significant
      relationship between pollen concentration and symptom scores were found (p >
      0.05). Positive correlations were seen between both Gramineae and Herb pollen,
      and humidity and rainfall from March to July. However, positive correlations were
      detected between tree pollen counts and temperature and humidity in May and June.
      CONCLUSION: This survey is the first volumetric airborne pollen analysis
      conducted in the survey area in Adana. This study suggested that the effects of
      weather on pollen count and symptom scores in this population could not be
      clearly identified with the evaluation of one-year data. However, pollen counts
      had effect on allergic symptoms in pollen allergic children. Examination of the
      complex interaction of multiple whether parameters would perhaps more fully
      elucidate the relationship between meteorology and aerobiology and provide the
      clinician with information necessary to forecast pollen prevalence. An awareness
      of the ever chancing, local aeroallergen patterns requires regular monitoring.
      Such awareness serves as a useful guide in the effective testing and treatment of
      atopic patients.

PMID- 15154618
TI  - Haptoglobin alpha-subunit and hepatocyte growth factor can potentially serve as
      serum tumor biomarkers in small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) frequently presents as metastatic
      disease. It would be useful to detect serum tumor biomarkers at an earlier stage
      in order to improve the overall survival. MATERIALS AND METHODS: Serum samples
      from SCLC patients (6 limited disease, 7 extensive disease, 4 relapsed disease, 4
      no evidence of disease post-treatment) and 5 normal controls were used to
      identify tumor biomarkers utilizing proteomics. Serum hepatocyte growth factor
      was also studied using standard ELISA. RESULTS: Utilizing MALDI-TOF-Mass
      Spectrometry (MS) based protein identification techniques, a SCLC specific
      overexpressed protein was identified to be haptoglobin alpha-subunit, with its
      serum level correlating with the disease stage. The mean level of alpha
      haptoglobin was increased in SCLC serum as compared to the normal controls. Serum
      HGF was also studied as potential tumor biomarker and was found to correlate with
      the disease status. Either serum alpha-haptoglobin relative level (above 1.9 U),
      or HGF level (above 500 pg/ml) was associated with a trend towards worse
      survival. CONCLUSION: Our current findings suggest that serum levels of alpha
      haptoglobin and HGF may serve as useful serum tumor biomarkers in SCLC. It would
      now also be useful to determine if these serum biomarkers are altered in response
      to therapy for this disease.

PMID- 15154619
TI  - Well-differentiated liposarcoma associated with benign lipoma.
AB  - The objective of this study was to review the clinicopathological features of
      seven patients presenting with well-differentiated liposarcoma (WDL), which was
      associated with subcutaneous lipoma. From 1980 through 2002, 34 individuals
      displaying WDL were treated in our institutions. Lipoma was observed in seven of
      these 34 patients (five men and two women, mean age of 66.7 years). The rate of
      co-existence of lipoma in WDL [20.6% (7/34)] cases was significantly higher than
      the corresponding rate in the other liposarcoma subtypes [2.5% (1/40)].
      Immunohistochemically, cdk4 was positive in all WDLs (100%). ki-67 was positive
      in 57.1% (4/7) and mdm2 and p53 were positive in 14.5% (1/7) of the WDL cases.
      Weak cdk4 immunoreactivity was detected in two lipomas. All lipomas were negative
      for mdm2, p53 and ki-67. Comparison of the expression profile in these malignant
      and benign tumors, which had arisen in identical genetic backgrounds, confirmed
      the involvement of these proteins, especially cdk4, in the tumorigenesis process
      of WDL.

PMID- 15154620
TI  - Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in
      human hepatocellular carcinoma.
AB  - One of the major obstacles in the treatment of hepatocellular carcinoma (HCC) is
      the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper
      transporting P-type adenosine triphosphate (ATP7B) has been reported to be
      associated with cisplatin resistance in vitro. However, the expression of ATP7B
      has not previously been addressed in human liver and HCC. Our purpose was to
      investigate ATP7B expression in human liver and hepatocellular carcinoma and its
      clinical significance. We retrospectively examined the expression of ATP7B in
      primary hepatocellular carcinoma. Immunohistochemical analysis of ATP7B was
      performed using a monoclonal antibody against ATP7B in 19 surgically removed
      hepatocellular carcinomas. A variable degree of cytoplasmic staining of tumor
      cells was observed in 21.1% (4/19) of the analyzed carcinomas. ATP7B expression
      was not observed in normal hepatic cells. Strong expression of ATP7B was observed
      in all the analyzed bile ducts. These findings suggest that overexpression of
      ATP7B in hepatocellular carcinoma might be associated with unfavorable clinical
      outcome in patients treated with cisplatin-based chemotherapy. Further, ATP7B is
      expressed in bile duct epithelial cells, where it may mediate copper secretion
      into bile fluid.

PMID- 15154621
TI  - Neuroendocrine tumors and second primary malignancy--a relationship with clinical
      impact?
AB  - BACKGROUND: Neuroendocrine tumors (NET) are frequently associated with
      synchronous or metachronous secondary primary malignancies (SPM). The aim of this
      study was to report on 14 patients with NET and SPM from a series of 96 patients
      with NET. PATIENTS AND METHODS: Fourteen patients with NET and synchronous or
      metachronous SPM were reviewed for primary site and characteristics of NET and
      associated SPMs as well as the outcome of these combined malignancies. RESULTS:
      From 1987 to 2002, 14 (14.6%) out of 96 patients with NET were identified with
      SPM. The median age of the patients at diagnosis of NET was 69 years (range: 56
      86 yrs). There were nine female and five male patients. The localization of NET
      was: four in appendix, three ileum, two duodenum, one stomach, one jejunum, one
      pancreatic tail, one rectum and one lung. Five patients had synchronous SPM (two
      colon cancers with one double colon cancer, one gastric cancer, one bladder
      cancer, one ovarian cancer) and nine metachronous SPM (two basal cell carcinomas,
      one colon cancer, two breast cancer, one gastric MALT-lymphoma, one ductal
      pancreatic adenocarcinoma, one bladder cancer, one hepatocellular carcinoma),
      three months to five years after diagnosis of NET. Five patients died of
      metastatic tumor (three SPM: 1, 7, 10 yrs; two NET: 1, 9 yrs), two patients died
      of other causes (1, 7 yrs), three patients are alive with metastatic tumor (two
      NET: 5, 6 yrs; one SPM: 10 yrs) while four patients are tumor-free (6 ms, 2, 9,
      10 yrs). CONCLUSION: NET is associated to a high degree with gastrointestinal and
      genitourinary SPM. In 5/14 (36%) patients SPM was diagnosed synchronously, while
      in 8/14 (57%) patients SPM was diagnosed metachronously. In 8/14 patients (57%)
      primary symptoms were caused by SPM. As a consequence, every NET should be
      regarded as an index tumor and risk-adapted follow-up with thorough
      investigation, mainly of the GI and genitourinary tracts, is to be recommended.

PMID- 15154622
TI  - CD44s expression is associated with improved survival in soft tissue sarcoma.
AB  - Expression of CD44 has been identified as a prognostic factor in several
      malignant diseases. Few studies have correlated CD44 expression in soft tissue
      sarcoma with subsequent tumor progression or recurrence. We sought to investigate
      the clinical significance of CD44s (standard) in adult soft tissue sarcoma (STS).
      Tumor specimens of 62 patients with STS were evaluated by immunohistochemistry
      for CD44s expression. The primary outcome measures were survival and local
      recurrence. Of 62 analyzed specimens, 49 tumors were CD44s-positive compared to
      13 CD44s-negative tumors. Kaplan-Meier survival analysis indicated significantly
      better survival among patients whose tumor was CD44s-positive (p=0.015). CD44s
      expression (hazard ratio, 3.1; 95% confidence interval, 1.5 to 7.0), tumor size
      (hazard ratio, 11.7; 95% confidence interval, 1.8 to 322) and resection quality
      (R1 vs. R0: hazard ratio, 8.7; 95% confidence interval, 3.1 to 24.5) were
      independent predictors of survival in multivariate analysis. CD44s expression
      correlates with prognosis of soft tissue sarcomas and therefore may have a
      pathogenetic role in tumor progression. Our results suggest that expression of
      CD44s in primary STS provides value regarding the progression of STS and,
      therefore, could be useful in selecting patients for adjuvant treatment.

PMID- 15154623
TI  - Comparison of carboxyterminal telopeptide of type I collagen (ICTP) and CA 125 as
      predictors of prognosis in ovarian cancer.
AB  - BACKGROUND: The clinical significance of the carboxyterminal telopeptide of type
      I (ICTP) as a predictor of prognosis is insufficiently known in ovarian cancer.
      Therefore, we compared the prognostic accuracy of ICTP and CA 125 and their
      combination with each other and with the aminoterminal propeptide of type III
      procollagen (PIIINP) and clinical prognosticators. PATIENTS AND METHODS: Fifty
      five epithelial ovarian cancer patients treated in Oulu University Hospital,
      Finland, from 1989-1995, were enrolled in this study. Cytoreduction was performed
      as completely as possible. The preoperative serum concentrations of the
      biochemical markers were determined using commercial kits. RESULTS: In univariate
      analysis, each biochemical marker and all conventional prognostic indicators,
      with the exception of histological subtype, correlated significantly with
      survival. In multivariate Cox analysis on biochemical and clinical markers, ICTP
      alone and ICTP + CA 125, but not CA 125 alone, proved useful indicators of
      overall survival. The combination of ICTP and CA 125, however, added no essential
      information compared to that obtained with ICTP alone. CONCLUSION: The ICTP test
      seems to be a clinically useful predictor of the clinical behavior of ovarian
      cancer. An increased serum ICTP concentration may reflect the spreading and
      aggressiveness of invasively growing ovarian cancer.

PMID- 15154624
TI  - Scatter factor receptor (c-Met) as possible prognostic factor in patients with
      oral squamous cell carcinoma.
AB  - This report was performed to study the biological role of c-Met in oral
      tumorigenesis by analyzing its expression in relation to clinicopathological
      features. Seventy-three cases of oral squamous cell carcinoma and 10 of normal
      mucosa were analysed for c-Met expression by immunohistochemistry. Normal oral
      squamous epithelium showed absent or low membranous positivity in the
      intermediate (malpighian-spinous) layer. Fifty-seven cases (78%) of carcinoma
      showed immunopositivity, with a prevalently membranous positivity and scattered
      areas also showing a cytoplasmic localization. Sixteen cases of carcinoma (22%)
      showed no positivity for c-Met. Among positive tumours, well-differentiated areas
      showed low or absent cytoplasmic positivity, while low-differentiated areas
      showed both membranous and cytoplasmic positivity. There was no statistically
      significant correlation between c-Met expression and sex, recurrence, staging or
      grading. The frequency of lymph node metastases was higher in c-Met-positive
      tumours (17/57, 29%) than in c-Met-negative ones (4/16, 25%). When analysed for
      prognostic significance, patients with negative/reduced c-Met expression had
      better survival rates than patients with high expression. The difference between
      survival rates was statistically significant (p<0.05). These data suggest that c
      Met expression may be useful to identify cases of oral squamous cell carcinoma
      with a more aggressive and invasive phenotype.

PMID- 15154625
TI  - Nuclear factor-kappaB p65 is a prognostic indicator in gastric carcinoma.
AB  - BACKGROUND: In common with other investigators, we have reported the constitutive
      activation of transcription factor nuclear factor-kappaB (NF-kappaB) in a variety
      of carcinomas, but there is no definite information on its clinical significance.
      MATERIALS AND METHODS: NF-kappaB p65 activation was determined by
      immunohistochemical analysis of surgically resected specimens from 63 gastric
      carcinomas. The 63 patients were divided into a high NF-kappaB group (21
      patients) and a low NF-kappaB group (42 patients). Forty-seven of the 63 patients
      underwent curative resection. The 47 patients consisted of 13 high NF-kappaB
      patients and 34 low NF-kappaB patients. RESULTS: The high NF-kappaB group
      demonstrated a shorter overall survival rate compared with the low NF-kappaB
      group (p=0.015). In the 47 patients who underwent curative resection, the high NF
      kappaB group also showed a poor survival prognosis (p=0.032). Multivariate
      analysis indicated that NF-kappaB activation is a potential prognostic factor in
      gastric carcinoma. CONCLUSION: Constitutive activation of NF-kappaB p65 may be a
      new prognostic parameter in gastric carcinoma.

PMID- 15154626
TI  - Male breast adenocarcinoma in a prostate cancer patient following prolonged anti
      androgen monotherapy.
AB  - We report the case of an 82-year-old male patient with a > 8-year history of
      prostate cancer (PrCa), who developed breast adenocarcinoma (BrCa) (Ki-67+ and
      negative for ER, PR, PSA and HER2/neu) after prolonged (approximately 7-year)
      anti-androgen (flutamide) monotherapy for locally advanced PrCa. Biochemical and
      molecular analyses showed hyperestrogenemia (serum estradiol = 266 pg/ml, with
      normal range < 74 pg/ml), germline BRCA-1 mutation (T to C at nucleotide 3232, in
      exon 11, causing Glu to Gly change at codon 1038) and chromosome 9 inversion
      (karyotype of 46,XY with inv(9) (p11q21)). Following bilateral mastectomy without
      adjuvant systemic therapy, the patient has been disease-free (from both BrCa and
      PrCa) for > 3 years. In contrast to LHRH-based hormonal therapies for PrCa, anti
      androgen monotherapy causes hyper-estrogenemia due to the suppressed negative
      feedback loop of androgens on LHRH and LH production, stimulation of testicular
      androgen production and their intracrine transformation to estrogens in
      peripheral target tissues. In this case report, the hyperestrogenemia may have
      further increased the BrCa risk in a patient with other risk factors (BRCA-1
      mutation and chromosome 9 inversion, which has been previously shown to impinge
      upon testicular function and intracrine balance of androgens vs. estrogens). This
      case report illustrates that PrCa patients receiving anti-androgen monotherapy
      may be at risk of BrCa, in the event of the concomitant presence of other
      genetically-determined predisposing factors, and indicates the importance of
      exercising caution against indiscriminate and prolonged use of anti-androgen
      monotherapy in patients with risk factors for male BrCa.

PMID- 15154627
TI  - Longitudinal changes in serum HER-2/neu oncoprotein levels in trastuzumab-treated
      metastatic breast cancer patients.
AB  - BACKGROUND: To evaluate longitudinal variations of serum HER-2/neu extracellular
      domain (sHER-2) in metastatic breast cancer patients receiving combined
      trastuzumab treatment. PATIENTS AND METHODS: Thirty-three patients were monitored
      by serial sHER-2 ELISA (Oncogene Science). Results were compared to time to
      progression (TTP) and survival from treatment initiation. Non parametric
      statistical tests were used. RESULTS: Median sHER-2 before first injection was
      41.37 ng/ml (range 7.54-1597.00 ng/ml, n=32). Mean sHER-2 levels differed
      significantly between responders (n=20) and non responders (n=13) (p<0.0001).
      Median TTP (266 days, range 35-1000 days) was unrelated to clinico-biological
      variables at diagnosis or number and site of metastases before treatment.
      Patients with pre-treatment sHER-2 levels < or = 30 ng/ml (n=14) had a
      significantly longer TTP than the group with sHER-2 > 30 ng/ml (n=18) (p=0.0346)
      and sHER-2 levels were of prognostic value for overall survival from first
      injection (p=0.0150). CONCLUSION: Our results show that monitoring serum HER
      2/neu levels during metastatic breast cancer can provide a real time assessment
      of a woman's HER-2/neu status and can provide important information for
      therapeutic decisions.

PMID- 15154628
TI  - Dehydropyrimidine dehydrogenase deficiency in a cancer patient undergoing 5
      fluorouracil chemotherapy.
AB  - We present a case of a Caucasian cancer patient undergoing 5-fluorouracil (5-FU)
      containing chemotherapy in our department. The 49-year-old female patient
      suffered from adverse effects representing WHO grade 3 toxicity. Genotyping
      revealed that she carried the exon 14-skipping mutation which is known to result
      in dehydropyrimidine dehydrogenase (DPD) deficiency. DPD is the enzyme that
      converts 5-FU to inactive metabolites and therefore dictates the amount of 5-FU
      that is available to be metabolised to cytotoxic nucleotides. Consequently DPD
      deficiency is the cause of severe adverse and sometimes lethal reactions to 5-FU.
      In conclusion the identification of cancer patients at increased risk of severe
      toxicity prior to the administration of 5-FU would be desirable.

PMID- 15154629
TI  - Testis metastasis as an initial manifestation of an occult gastrointestinal
      cancer.
AB  - Metastatic epithelial malignant tumor involving the spermatic cord and epididymis
      is rare and the prognosis of these patients is poor. Usually gastrointestinal
      cancers show diffusion to liver, lung and bone. Several routes by which a
      colorectal cancer can metastasize to the testis have been reported in literature.
      Herein we report a case of an occult gastrointestinal cancer with an intrascrotal
      metastasis in an adult patient with possible spread through the spermatic veins
      due to primary intestinal carcinoma. In the case of a testicular mass or
      hydrocele evidence in a patient with an unusual age for primary testis tumor, a
      diagnosis of metastatic cancer should be considered.

PMID- 15154630
TI  - Expression and prognostic value of the lung resistance-related protein (LRP) in
      germ cell testicular tumors.
AB  - BACKGROUND: Lung resistance-related protein (LRP) was first detected in a non-P
      glycoprotein-mediated multidrug-resistant lung cancer cell line and has been
      shown to be the major human vault protein. The aim of this study was to evaluate
      the expression of LRP in germ cell testicular tumors (GCT) and to determine the
      correlation between LRP expression and the clinical outcome of these tumors.
      PATIENTS AND METHODS: Seventy cases of primary testicular tumors were
      investigated. LRP protein was detected by immunohistochemistry and Western
      blotting methods. LRP mRNA was determined with RT-PCR. Patients' clinical
      parameters and tumor response to treatment were recorded. RESULTS: With
      immunohistochemistry, LRP was detected in 29 (41%) out of 70 primary testicular
      tumors. Twenty-two (63%) out of 35 tumors expressed LRP mRNA and LRP protein on
      examination by RT-PCR and Western blotting, respectively. Pure teratomas showed
      significantly higher LRP expression compared to other types of GCTs (p=0.0418).
      No relationship was demonstrated between the LRP immunostaining and stage of
      disease (p=0.2263). A significantly higher proportion of patients with LRP
      negative tumors achieved complete response than those with LRP-positive tumors
      (p=0.0155). Patients whose tumors showed expression of LRP had significantly
      shorter overall survival (p=0.0428) than LRP-negative patients. CONCLUSION:
      Immunohistochemistry is a reliable method to evaluate LRP expression in
      testicular germ cell tumors. A positive correlation was found between LRP
      immunostaining and pure teratomas. LRP expression was associated with an adverse
      clinical outcome and shorter overall survival. Our findings suggest that LRP has
      prognostic value in testicular germ cell tumors and can predict clinical outcome.

PMID- 15154632
TI  - Galectin-3 immunodetection may improve cytological diagnosis of occult papillary
      thyroid carcinoma.
AB  - Galectin-3 has been found recently to be neo-expressed in thyroid cancers
      compared to benign lesions and it could therefore be considered a marker of
      malignancy. We report the case of a 36-year-old woman with a history of
      occasional dysphagia and dysphonia first observed in November 2000. Thyroid
      ultrasound scan revealed two subcentimetric nodules in the right lobe. The larger
      one underwent ultrasound-guided fine-needle aspiration cytology (FNAC). Due to
      the nature of the lesion, only a few cells could be collected. Their
      morphological aspect was suspicious but not conclusive for malignancy, therefore
      we marked the cells using a monoclonal antibody anti-galectin-3. The cytological
      suspicions were supported by galectin-3-expressing cells, so the patient was
      referred to surgery. The final histological diagnosis was conclusive for
      multifocal occult thyroid papillary carcinomas. We conclude that the galectin-3
      immunocytochemical assay should be part of the diagnostic protocol supporting
      conventional cytology to characterize scanty and/or suspicious cellular smears.

PMID- 15154631
TI  - Primitive neuroectodermal tumor (PNET) treated with interferon-beta after
      surgical removal and irradiation: case report.
AB  - This case report describes an 11-year-old boy with primitive neuroectodermal
      tumor (PNET), which remains the pediatric brain tumor with the worst prognosis
      despite combination treatment with surgery, irradiation and anti-cancer drugs.
      The boy was successfully treated with intratumoral administration of interferon
      beta (IFN-beta) following surgical resection and irradiation. Two million units
      of IFN-beta were locally administered into the post-operative cavity through the
      Ommaya's reservoir every two weeks after discharge. He was managed as an
      outpatient without serious side-effects to IFN. The patient has shown no tumor
      recurrence, mental retardation, or neuroendocrine impairment for over three years
      and has lived a normal school life with a full Karnofsky Performance Status
      score. The local administration of IFN-beta may be warranted for maintenance
      therapy in children with PNET.

PMID- 15154633
TI  - Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR
      improves accuracy in detection of peritoneal micrometastasis of gastric cancer.
AB  - Peritoneal metastasis is the most frequent form of recurrence for advanced
      gastric cancer. We previously performed a global analysis of the gene expression
      of gastric cancer cell lines established from peritoneal metastasis with cDNA
      microarray. One of the up-regulated genes is L-3-phosphoserine phosphatase (L3
      PP). We have examined its potential as a novel marker for the detection of
      peritoneal micrometastasis of gastric cancer. L3-PP mRNA in peritoneal wash from
      88 gastric cancer patients was quantified for comparison of carcinoembryonic
      antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently-labeled
      probe to predict peritoneal recurrence. The quantity of L3-PP and CEA correlated
      with wall penetration. The cut-off value was set at the upper limit of the
      quantitative value of T1 cases (tumor invades within submucosa) and those above
      the cut-off value constituted the micrometastasis (MM+) group; eight out of 14
      cases with peritoneal dissemination were MM+ L3-PP (57.1% sensitivity) and two
      out of 57 T1 and T2 cases were MM+ (93% specificity). For two out of 14 cases of
      peritoneal dissemination only L3-PP could detect micrometastasis of gastric
      cancer, indicating that L3-PP is superior to CEA especially in poorly
      differentiated adenocarcinoma. The combination of CEA and L3-PP improved the
      accuracy of diagnosis up to 85.7%. Consequently, free cancer cells that cannot be
      detected by CEA mRNA could be detected using L3-PP mRNA. CEA alone was not
      sufficient, but L3-PP and CEA in combination can attain a higher accuracy of
      detection.

PMID- 15154634
TI  - Deamination of glutamine is a prerequisite for optimal asparagine deamination by
      asparaginases in vivo (CCG-1961).
AB  - BACKGROUND: Glutamine (Gln) deamination by asparaginase (ASNase) appears to
      contribute in the decrease of serum asparagine (Asn) levels and enhance leukemic
      cell apoptosis. The pharmacodynamic (PD) rationale is based on the role of Gln as
      the main amino group donor for Asn synthesis from aspartate by the enzyme
      asparagine synthetase (AS). MATERIALS AND METHODS: Relationships between ASNase
      enzymatic activity and Asn or Gln levels were examined in 274 pairs of pre- and
      post-ASNase serum specimens from 200 high-risk acute lymphoblastic leukemia (ALL)
      patients from the Children's Cancer Group (CCG-1961). Data were analyzed
      according to a novel PD model based on previous best-fit projections (NONMEM)
      from the CCG-1962 standard-risk ALL study. RESULTS: The PD results from high-risk
      and standard-risk ALL patients were superimposable. The percentages of Asn and
      Gln deamination were predicted by ASNase activity in patients' sera.
      Pharmacodynamic analyses strongly suggested that > 90% deamination of Gln must
      occur before optimal Asn deamination takes place in vivo. Asparaginase activity >
      or = 0.4 IU/ml yielded mean Gln and Asn % deamination values of 90%. Lower ASNase
      concentrations yielded lower Gln or Asn % deamination. This ASNase concentration
      coincides with the in vitro determined IC50 value on CEM/0 human T-lymphoblastic
      leukemia cells. CONCLUSION: Asparaginase activity of > or = 0.4 IU/ml provided
      optimal Asn and Gln deamination in high-risk ALL patients. Deamination of Gln
      correlates with enhanced serum Asn deamination in vivo. Therefore, deamination of
      Gln may enhance the antileukemic effect of ASNase.

PMID- 15154635
TI  - Monitoring of serum Her-2/neu predicts histopathological response to neoadjuvant
      trastuzumab-based therapy for breast cancer.
AB  - BACKGROUND: This prospective pilot study was performed to elucidate whether early
      changes in serum levels of the Her-2/neu extracellular domain (ECD) reflect
      histopathological response to trastuzumab-based neoadjuvant therapy in patients
      with Her-2/neu-overexpressing breast cancer. PATIENTS AND METHODS: ECD levels
      were measured throughout neoadjuvant trastuzumab-based treatment in 16 patients
      using a Her-2/neu Microtiter ELISA. RESULTS: In 9 (56%) patients with Her-2/neu
      shedding tumors (ECD > 15 ng/ml), ECD values (in % of baseline) of non-responders
      vs. responders were 117% vs. 55% on day 8 (p=0.014), 157% vs. 58% on day 22
      (p=0.061) and 114% vs. 46% at restaging (p=0.049). CONCLUSION: Serial monitoring
      of serum Her-2/neu ECD levels may represent a valuable tool to predict
      pathological response to trastuzumab-based neoadjuvant therapy in patients with
      Her-2/neu-overexpressing tumors.

PMID- 15154636
TI  - Prophylactic efficacy of allopurinol ice ball for leucovorin/5-fluorouracil
      therapy-induced stomatitis.
AB  - BACKGROUND: Stomatitis in cancer chemotherapy manifests with pronounced
      subjective symptoms, lowers the patient's quality of life (QOL) and may
      necessitate the discontinuation of chemotherapy. There have been few effective
      therapies established to date for chemotherapy-induced stomatitis. PATIENTS AND
      METHODS: We used frozen allopurinol solution (allopurinol ice balls) in the
      prevention of stomatitis associated with leucovorin (LV)/5-fluorouracil (5-FU)
      therapy for colon cancer. RESULTS: Among 32 patients undergoing LV/5-FU therapy,
      without the use of the allopurinol ice balls, 15 patients developed stomatitis.
      On the other hand, only 3 patients developed stomatitis among 20 patients
      receiving the chemotherapy in conjunction with allopurinol ice balls (p=0.0187).
      Seven patients who developed stomatitis during a course of chemotherapy without
      allopurinol ice balls were administered the ice balls in the subsequent course; 6
      of these patients responded with lessened severity of stomatitis. In 2 of these
      responders, stomatitis of comparable severity recurred on discontinuation of the
      medication. CONCLUSION: Concomitant use of allopurinol ice balls is effective in
      preventing stomatitis in patients undergoing LV/5-FU therapy.

PMID- 15154637
TI  - Stevens-Johnson syndrome induced by paclitaxel in a patient with squamous cell
      carcinoma of the lung: a case report.
AB  - We treated a 53-year-old man with advanced squamous cell carcinoma of the lung
      who had developed Stevens-Johnson syndrome, a life-threatening cutaneous
      reaction, after systemic chemotherapy consisting of carboplatin and paclitaxel. A
      critical assessment disclosed circumstantial evidence pointing to paclitaxel as
      the likely cause of this complication. As far as we are aware, this account is
      the first description of a paclitaxel-induced Stevens-Johnson syndrome. This case
      serves as an alert for the need to observe patients closely for potentially
      dangerous cutaneous reactions to paclitaxel therapy.

PMID- 15154638
TI  - Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil
      refractory metastatic colorectal adeno-carcinoma.
AB  - BACKGROUND: This study evaluated the antitumor efficacy and safety of a novel
      oxaliplatin/raltitrexed combination in pretreated advanced colorectal cancer
      patients. PATIENTS AND METHODS: Forty-five patients with 5-fluorouracil
      refractory metastatic colorectal cancer received raltitrexed 3.0 mg/m2 as a 15
      minute intravenous (i.v.) infusion, followed 45 min later by l-OHP 130 mg/m2 i.v.
      as 2-h venous infusion on 1 day every 3 weeks. All patients had histologically
      proven metastatic colorectal cancer, age 18-75, measurable disease and normal
      baseline biological values. Most patients (60%) had >2 disease sites. All
      patients were assessed for safety and also for response according to an intent-to
      treat fashion. RESULTS: The overall response rate was 29% (95% CL 16%-44%)
      including one CR (2%) and 12 PR (27%). Six patients (16%) showed a stabilization
      of disease for a tumor growth control rate of 45%. The median time to progression
      was 4 months (range 1-12+) and median overall survival was 9 months (range 1
      29+). CONCLUSION: These data confirm that this oxaliplatin/raltitrexed
      combination is effective against metastatic colorectal carcinoma, well tolerated
      with low grade toxicity and easy to administer. Further evaluation of this
      regimen seems warranted as an alternative to fluoropyrimidine-based combinations.

PMID- 15154639
TI  - Treatment of glioblastoma with intravenous taurolidine. First clinical
      experience.
AB  - BACKGROUND: Despite progress in diagnosis and therapy, the prognosis of patients
      with glioblastoma remains poor. Recently it has been found that the antibacterial
      agent taurolidine has a direct and selective antineoplastic effect on brain tumor
      cells by the induction of programmed cell death. This paper reports on
      intravenous taurolidine treatment in two patients with a progressive glioblastoma
      despite conventional therapy. PATIENTS AND METHODS: Two male patients with
      histopathologically diagnosed glioblastoma were included. The tumors were
      progressive despite conventional therapy. Intravenous taurolidine treatment was
      initiated. RESULTS: The neurological condition and quality of life improved in
      both patients such that they could be discharged for further outpatient
      treatment. Follow-up demonstrated partial remission of the tumor in both
      patients. However, both patients died about 4 months following the start of
      taurolidine treatment, from pneumonia and acute thrombembolism, respectively.
      CONCLUSION: Both patients achieved a transient, marked improvement in quality of
      life and partial tumor remission. There was a clear response to the taurolidine
      treatment.

PMID- 15154640
TI  - Vascular endothelial growth factor (VEGF) concentration in sera and tumor
      effusions from patients with ovarian carcinoma.
AB  - VEGF is an important angiogenic cytokine with a critical role in tumor
      angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting
      VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients
      with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF
      levels were significantly elevated in the sera and cyst fluids of carcinoma
      patients compared with patients who had benign neoplasms. In carcinoma patients,
      statistically higher VEGF levels were detected in tumor effusions than in
      corresponding sera. The differences between VEGF values in sera and tumor
      effusions in relation to histological subtypes of ovarian carcinoma and FIGO
      stages were statistically insignificant. High VEGF levels in ascitic fluids
      appeared to be significantly associated with shorter disease-free survival and
      overall survival In multivariate analysis, besides FIGO stage and age of
      patients, only serum VEGF concentration was an independent prognostic factor for
      overall survival. The elevated VEGF levels in sera and tumor effusions of
      patients with FIGO stages I/II indicated that angiogenesis promoted by VEGF is a
      continuous process, independent of clinical advancement of the disease.

PMID- 15154641
TI  - A protein chip system for parallel analysis of multi-tumor markers and its
      application in cancer detection.
AB  - BACKGROUND: Tumor markers are routinely measured in clinical oncology. However,
      their value in cancer detection has been controversial largely because no single
      tumor marker is sensitive and specific enough to meet strict diagnostic criteria.
      One strategy to overcome the shortcomings of single tumor markers is to measure a
      combination of tumor markers to increase sensitivity and look for distinct
      patterns to increase specificity. This study aimed to develop a system for
      parallel detection of tumor markers as a tool for tumor detection in both cancer
      patients and asymptomatic populations at high risk. MATERIALS AND METHODS: A
      protein chip was fabricated with twelve monoclonal antibodies against the
      following tumor markers respectively: CA125, CA15-3, CA19-9, CA242, CEA, AFP,
      PSA, free-PSA, HGH, beta-HCG, NSE and ferritin. Tumor markers were captured after
      the protein chip was incubated with serum samples. A secondary antibody
      conjugated with HRP was used to detect the captured tumor markers using
      chemiluminescence technique. Quantification of the tumor markers was obtained
      after calibration with standard curves. RESULTS: The chip system showed an
      overall sensitivity of 68.18% after testing 1147 cancer patients, with high
      sensitivities for liver, pancreas and ovarian tumors and low sensitivities for
      gastrointestinal tumors, and a specificity of 97.1% after testing 793 healthy
      individuals. Application of the chip system in physical checkups of 15,867
      individuals resulted in 16 cases that were subsequently confirmed as having
      cancers. Analysis of the detection results with a Support Vector Machine
      algorithm considerably increased the specificity of the system as reflected in
      healthy individuals and hepatitis/cirrhosis patients, but only modestly decreased
      the sensitivity for cancer patients. CONCLUSION: This protein chip system is a
      potential tool for assisting cancer diagnosis and for screening cancer in high
      risk populations.

PMID- 15154642
TI  - Local excision of rectal cancer with transanal endoscopic microsurgery (TEM).
AB  - BACKGROUND: Local excision for T1 rectal cancers with Transanal Endoscopic
      Microsurgery (TEM) is an accepted standard of care. However for T2/T3 rectal
      cancers, the high local failure indicates that this is not a valid option.
      MATERIALS AND METHODS: Between 1990 and 2000, 83 patients with rectal
      adenocarcinoma underwent complete full thickness local excision. The mean
      diameter of the tumor was 3.4+/-1.7 cm, 60% were located more than 5 cm from the
      anal verge; 43% of patients received radiation therapy (26 pre- and 10
      postoperatively). RESULTS: Postoperative complications occurred in 15 patients
      (18%); there were no postoperative deaths. Mean follow-up was 37 months (range 18
      118). The pathological stage was: Tis 9, T1 39, T2 23, T3 12. The overall local
      recurrence rate was 0% for Tis, 13% for T1, 17% for T2 and 50% for T3. Recurrence
      was managed surgically in 65% and nonsurgically in 35% because of advanced
      disease or poor general condition. Overall 5-year survival rates were 100%, 92%,
      75% and 69% for Tis, T1, T2 and T3, respectively. CONCLUSION: Local excision with
      TEM is effective for early (Tis, T1) rectal cancers. Patients with T2 tumors can
      be treated with preoperative chemoradiation and subsequently local resection.
      Patients with T3 should not be treated with local excision unless they are unable
      to tolerate more extensive surgery.

PMID- 15154643
TI  - The dissociated expression of protein and messenger RNA of DPC4 in human invasive
      ductal carcinoma of the pancreas and their implication for patient outcome.
AB  - BACKGROUND: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated
      in about half of invasive ductal carcinoma (IDC) of the pancreas, but the
      expression of DPC4-mRNA remains to be evaluated. The present study assessed the
      comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their
      implication for patient outcome. MATERIALS AND METHODS: In the freshly separated
      specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs,
      the expression of mRNA was assessed by in situ hybridization and the expression
      of pDpc4 was assessed by immunohistochemistry. RESULTS: In the freshly separated
      specimens, DPC4-mRNA was expressed in 71% of the IDC, but pDpc4 expression was
      lost in 76% of the IDC. In 88 resectable IDCs, pDpc4 expression was lost in 75
      (85.2%) and loss of pDpc4 expression was significantly correlated with the grade
      of nodal involvement (p =0.0265). Furthermore, the survival rate of the pDpc4 (-)
      group was significantly lower than that of the pDpc4 (+) group (p=0.0391).
      Adjuvant chemotherapy (ACT) significantly improved the survival rate and, in the
      ACT group, pDpc4 (-) patients had a significantly lower survival rate than the
      pDpc4 (+) patients. CONCLUSION: In human pancreatic IDC, although DPC4-mRNA was
      usually expressed, the expression of pDpc4 was lost. The expression of pDpc-4 is
      an indicator of better prognosis and response to ACT.

PMID- 15154644
TI  - Detectable serum PSA after radical prostatectomy. Clinical and pathological
      relevance of perianastomotic biopsies.
AB  - BACKGROUND: Few reports have detailed the histopathological results of biopsies
      of the vesicourethral anastomosis or prostatic bed in patients with a detectable
      postoperative PSA. PATIENTS AND METHODS: Among a series of 153 patients who
      underwent radical retropubic prostatectomies, we analyzed the results of 64
      perianastomotic biopsies performed in 17 men with a detectable PSA and no
      evidence of local recurrence or distant metastases. RESULTS: Fourteen of the 17
      patients had a relapse of prostatic carcinoma; the results of histology in the
      three pT2bN0M0 patients revealed the presence of benign prostatic hyperplasia in
      2 patients and atypical cribriform proliferation in 1 patient. The first two
      patients are free from prostatic cancer recurrence 36 months after
      perianastomotic biopsies; a further biopsy performed 6 months after in the third
      patient showed the presence of prostatic carcinoma. CONCLUSION: The present study
      raises the possibility that residual benign tissue, resulting from unintentional
      disruption of the prostatic capsule during surgery, may be responsible for a
      detectable postoperative PSA. These cases comprise a histopathological
      classification described as "intraprostatic surgical margin".

PMID- 15154645
TI  - Impact of mistletoe lectin binding in breast cancer.
AB  - BACKGROUND: One of the most often used complementary or alternative anticancer
      therapeutics for breast cancer is mistletoe extract with Viscum album lectin (VAA
      1) as the leading component. The aim of this study was to determine the
      correlation between VAA-1 binding in breast cancer and disease outcome. MATERIALS
      AND METHODS: VAA-1 binding to either tumour cells or tumour infiltrating
      inflammatory cells was examined by immunohistochemical staining of paraffin
      tissue sections from breast cancer patients (n=226). RESULTS: About 34% of breast
      cancer tumour cells displayed a strong VAA-1 binding. Kaplan-Meier statistics
      revealed an inverse correlation between disease outcome and presence of strong
      VAA-1 binding to tumour cells. CONCLUSION: As binding of VAA-1 indicates the
      presence of galactose molecules in saccharide structures of the cytoplasm or cell
      membrane, we conclude that the amount of galactose-containing glycoproteins,
      mucoproteins and glycolipids in breast cancer tumour cells is related to disease
      outcome.

PMID- 15154646
TI  - Host-oriented peptide evaluation using whole blood assay for generating antigen
      specific cytotoxic T lymphocytes.
AB  - A whole blood assay using antigenic peptide was established to predict host
      cytotoxic T lymphocyte (CTL) precursor status. Blood samples from HLA-A24 donors
      and colorectal cancer patients were directly diluted with RPMI-1640 medium to a
      20% blood concentration, then distributed to tubes and a peptide of an HLA-A24
      restricted CEA peptide panel (20 microM) was added to the tubes. Incubation was
      performed for 4-5 days and supernatants were subjected to ELISA specific for IFN
      gamma protein. It was observed that certain CEA peptides could stimulate the
      diluted blood samples to produce IFN-gamma. Only the peripheral blood mononuclear
      cells (PBMCs) that were purified from the IFN-gamma-positive samples of the whole
      blood assay showed positive spots, detected with IFN-gamma ELISPOT assay, and
      could proliferate with the stimulation of immobilized anti-CD3 antibody plus
      interleukin-2 (CD3/IL-2 system). The proliferating PBMCs expressed cytotoxic
      activity against HLA-A24+ CEA-expressing tumor cells and the TISI target cells
      pulsed with the CEA peptide that had been used to stimulate the PBMCs to produce
      IFN-gamma, but they did not kill the target cells pulsed with peptides that had
      failed to stimulate IFN-gamma production, nor did they kill the target cells
      alone. Theses findings suggest that the IFN-gamma production of the blood samples
      detected by the whole blood assay identifies the peptide that can induce the CEA
      antigen-specific CTL response. Detection of IFN-gamma gene expression using real
      time-PCR analysis could identify the peptide within 6 hours, which is earlier
      than the protein analysis by ELISA. The whole blood assay using the CEA peptide
      panel for healthy donors and colorectal cancer patients revealed that IFN-gamma
      inducible peptides were different among the individual samples tested, indicating
      that the CEA peptides that should be used for generating CTLs are different in
      individual patients. The whole blood assay using a CEA antigen peptide panel is
      simple and beneficial for identifying candidate peptides. The host-oriented
      peptide evaluation (HOPE) approach may provide hope for the augmentation of
      clinical efficacies for peptide-based cancer immunotherapy.

PMID- 15154647
TI  - p53 analysis in gallbladder cancer: comparison of gene analysis versus
      immunohistochemistry.
AB  - BACKGROUND: The survival of gallbladder cancer (GC) patients is generally poor.
      Both after resection and palliative procedures, additive therapy is often
      administered to increase outcome. The effect of cytotoxic therapies depends on a
      functioning p53 gene. The aim of this study was to investigate whether p53
      immunohistochemistry (IHC) or p53 gene sequencing are of any survival influence
      in GC. PATIENTS AND METHODS: In 61 GC patients, 19 were resected and in 42
      operative explorations were performed. Seven resected and 14 palliated patients
      received adjuvant chemotherapy. IHC p53 staining and DNA sequencing was
      investigated. RESULTS: p53 sequencing detected 20 mutations and no relationship
      was found between IHC and sequencing results. After resection chemotherapy
      increased survival in those having a normal p53 gene compared to those having a
      mutation (p=0.008). p53 status did not show an influence in resected patients
      without chemotherapy or in palliative-treated patients regardless of their
      therapy. CONCLUSION: p53 protein overexpression does not correlate with p53 gene
      mutation. Response to chemotherapy in resected GC patients may depend on a
      functioning p53 gene.

PMID- 15154648
TI  - Prevalence of Chlamydia pneumoniae infection in squamous cell carcinoma of the
      head and neck.
AB  - On the basis of epidemiological data, an association between Chlamydia pneumoniae
      (Cp) infection and head and neck cancer might be suggested. The aim of the
      present study was to detect Cp-DNA within tumour tissue specimens by a two-step
      polymerase chain reaction. Investigation was planned on the Fleming's procedure
      for early termination when initial results were extreme. So, after ten
      consecutive patients, only one tumour contained Cp-DNA. Hence the prevalence
      could be regarded as inferior to 60% (2a=b=0.08), the threshold under which a
      direct role of Cp in head and neck cancer development does not seem to be likely.

PMID- 15154649
TI  - Weekly docetaxel as second-line chemotherapy in advanced non-small cell lung
      cancer: phase II trial.
AB  - BACKGROUND: Open-label, single-centre Phase II trial evaluating the toxicity and
      antitumour activity of weekly docetaxel in the second-line management of advanced
      non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment comprised
      docetaxel 35 mg/m2 weekly for 6 weeks followed by 2 weeks' rest for a maximum of
      3 cycles. RESULTS: Thirty-six patients received 220 weekly doses of docetaxel.
      Toxicity was generally mild: no grade 3-4 haematological toxicity; one grade 4
      non-haematological event (bloody diarrhoea in a patient with pre-existing colon
      diverticulitis). Nausea (11%) and asthenia (8%) constituted the main grade 3 non
      haematological toxicities. The objective response rate was 11% (14% minor
      response, 25% stable disease) and the median duration of survival upon the
      initiation of docetaxel was 160 days, with a 1-year survival rate of 23%.
      CONCLUSION: Docetaxel is active and well tolerated in the second-line treatment
      of advanced NSCLC and appears to yield an improved therapeutic index versus 3
      weekly regimens.

PMID- 15154650
TI  - Molecular prognostic factors in locally irresectable rectal cancer treated
      preoperatively by chemo-radiotherapy.
AB  - PURPOSE: The aim of this study was to determine the relationship between survival
      and value of molecular markers in the primary tumour in a group of patients with
      irresectable rectal cancer, treated with preoperative chemo-radiotherapy.
      MATERIALS AND METHODS: Immunohistochemistry for p53, p21, bcl-2 and Ki-67 was
      performed on pre-treatment biopsy specimens of 34 patients with irresectable
      rectal cancer. Preoperative treatment consisted of pelvic irradiation of 45-56
      Gy, combined with 5FU and leucovorin (350/20 mg/m2 x 5 d; in weeks 1 and 5 during
      radiotherapy). The median follow-up was 38 months. Endpoints were pathological T
      stage and survival after surgery. RESULTS: Expression of p21 correlated
      significantly with survival (p=0.005). Survival and p21 expression also
      correlated significantly, when adjusted for tumour response (p=0.005, RR=4.8 (1.6
      14.7)). CONCLUSION: Expression of p21 predicts a worse survival in irresectable
      rectal cancer treated with preoperative chemo-radiotherapy. No relationship was
      found between tumour response in chemo-radiotherapy and p53, bcl-2 or Ki-67.

PMID- 15154651
TI  - Granulosa cell tumor of the ovary: 10 years follow-up data of 65 patients.
AB  - BACKGROUND: Granulosa cell tumor of the ovary is an uncommon neoplasm. The
      majority of patients are diagnosed in early stages of disease and overall
      prognosis is favorable. The stage at time of diagnosis is the only prognostic
      factor that is unequivocally related to survival. Other prognostic factors have
      not been well defined and are discussed in the literature controversially.
      MATERIALS AND METHODS: In a multi-institutional retrospective study we analyzed
      all relevant clinical data of patients with histologically proven granulosa cell
      tumor of the ovary. We applied the Kaplan-Meier method in order to estimate
      overall survival rates and evaluate prognostic factors. RESULTS: The median
      follow-up was 75 months (range, 6-315 months). Overall survival was 87% and 76%
      after 5 and 10 years, respectively. Eighty percent of granulosa cell tumors were
      diagnosed stage I (FIGO). The survival rate after recurrence was 56.8% after 10
      years. Mitotic rate (p=0.003), tumor stage (p<0.001) and residual tumor disease
      (p<0.001) were associated with a poor prognosis (p<0.001). Age and rupture of the
      tumor could not be confirmed to be of prognostic value. CONCLUSION: The results
      of our study showed that the mitotic index may be a valuable prognostic factor.
      Complete tumor resection should always be attempted, since residual tumor disease
      is associated with a poor prognosis. Prospective studies are needed in order to
      confirm our findings.

PMID- 15154652
TI  - Cellular immunomodulation and safety of standardized aqueous mistletoe extract
      PS76A2 in tumor patients treated for 48 weeks.
AB  - Non-selected tumor patients (n=12) with various solid carcinomas were treated
      continuously twice weekly over 48 weeks with the aqueous mistletoe extract
      PS76A2, standardized to active mistletoe lectin. The preparation was applied
      subcutaneously at a concentration of 15 ng mistletoe lectin per 0.5 ml. Cellular
      immune response and safety were determined at various times during and after the
      therapy. In the course of treatment, virtually all the investigated
      immunoparameters were raised compared to the baseline values at the start of
      treatment. The statistically significant rises in the cell count of total
      lymphocytes, monocytes and natural killer (NK) cells was noteworthy. The
      differences in comparison with the baseline values at the various measuring times
      during treatment were up to 35%. In the first weeks of treatment at least, the
      raised cell count of NK cells correlated with the significantly increased
      cytotoxic activity versus tumor cells ex vivo. The NK factor (product of NK cells
      and ex vivo activity) was determined to assess the total NK activity more
      accurately, which rose up to 50% compared to the baseline value. Other lymphatic
      subpopulations, for instance CD3+, CD8+, CD3+CD4+ and CD3+CD8+ cells, also
      revealed distinct rises in cell count in the course of treatment. Within 6 weeks
      after completion of treatment, the overall values dropped again; but for a series
      of immunoparameters--in particular for the NK cells--they were still raised in
      comparison to the baseline values. The extensive laboratory diagnostics
      (haematology, clinical chemistry) showed that treatment with the standardized
      mistletoe extract PS76A2 was well tolerated by all patients. In single cases,
      local reactions at the injection sites were of a minor nature and reversible
      within two days. Summarizing, it can be stated that the standardized mistletoe
      extract PS76A2 significantly improved the immune status of tumor patients and was
      administered safely over a long period.

PMID- 15154653
TI  - Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung
      carcinoma: a phase II study.
AB  - BACKGROUND: Taxanes have been widely used against advanced non-small cell lung
      cancer (NSCLC), alone and in combination with platinum agents. In order to
      develop a tolerable palliative regimen, we combined carboplatin with low dose
      docetaxel. PATIENTS AND METHODS: Chemotherapy-naive patients, with Stage IIIB or
      IV NSCLC and an ECOG performance status < or = 2, were enrolled. Treatment
      consisted of docetaxel 60 mg/m2 and carboplatin AUC 6 every 21 days. Therapy
      continued for 1 year or 6 months beyond best response, whichever was greater.
      RESULTS: Twenty-five patients were enrolled. Most patients (80%) had Stage IV
      disease. The partial response rate was 16%. Response duration ranged from 6 to
      115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade
      3 or 4 neutropenia. There was 1 septic death. CONCLUSION: Survival compared
      favorably to other similar trials employing higher doses of docetaxel.
      Additionally, a hematologic toxicity advantage was seen compared to regimens
      containing higher doses of docetaxel.

PMID- 15154654
TI  - Prognostic significance of soluble adhesion molecules in Hodgkin's disease.
AB  - BACKGROUND: Cell adhesion may play a pivotal role in the development, progression
      and metastasis of solid malignancies. We evaluated the serum concentration of
      four adhesion molecules and their prognostic significance in patients with
      Hodgkin's Disease (HD). PATIENTS AND METHODS: Serum samples from 20 HD patients
      were collected at diagnosis, after 3 cycles of chemotherapy and at completion of
      treatment and compared with a control group of 29 apparently healthy subjects.
      Soluble forms of E-Selectin (sE-Selectin), ICAM-1 (sICAM-1), VCAM-1 (sVCAM-1) and
      E-Cadherin (sE-Cad) were measured by standard ELISA assays. RESULTS:
      Significantly increased serum levels of sICAM-1 and sE-Selectin were determined
      in HD patients at diagnosis compared to controls (p<0.0001), while sVCAM-1 at
      diagnosis correlated significantly with both sICAM-1 and sE-Selectin levels
      (r=0.5, p=0.03). Chemotherapy resulted in a significant decrease of sICAM-1 and
      sE-Selectin levels (p=0.02 and p=0.002, respectively). CONCLUSION: Serum levels
      of ICAM-1 and E-Selectin in newly diagnosed HD patients were found significantly
      increased, suggesting a possible involvement of these two molecules in the
      pathogenesis of the disease. Their rapid decrease following chemotherapy was
      found to be an independent predictor of response to treatment.

PMID- 15154655
TI  - Pre-irradiation chemotherapy for newly diagnosed high grade astrocytoma.
AB  - The purpose of this work was to determine the response rate and toxicity of a
      combination of Carmustine and Cisplatin administered before radiation in patients
      with newly diagnosed high grade astrocytoma. A good response rate has been
      published with this association in primary cerebral high grade tumor. This
      protocol was administered in a homogeneous population of 37 adult patients with
      measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or
      subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d,
      for 3 days every 28 days for 3 cycles. Evaluation was performed before each
      cycle. Radiation therapy began 4 weeks after completing the chemotherapy or
      immediately if there was evidence of tumor progression on chemotherapy. Seven out
      of 37 (19%) demonstrated tumor regression with a median duration to progression
      of 11 months. Median survival was 6 months. Myelosuppression was the predominant
      but manageable toxicity. This work indicated that the first chemotherapy protocol
      gave poor results in a homogeneous group of patients, with bad prognosis.

PMID- 15154656
TI  - Treatment with all-trans retinoic acid plus tamoxifen and vitamin E in advanced
      hepatocellular carcinoma.
AB  - BACKGROUND: Low serum retinol and hepatic tocopherol levels correlate with
      hepatocellular carcinoma (HCC) risk. Antiestrogen tamoxifen seems useful in HCC
      patients. A pilot study was performed to evaluate the effect of all-trans
      retinoic acid associated with tamoxifen and vitamin E on patients with advanced
      HCC. PATIENTS AND METHODS: Fifteen consecutive patients with advanced HCC were
      included in the study. Patients were evaluated for survival, quality of life,
      liver function, tumor mass, toxicity related to the treatment and retinoid
      receptors in liver biopsies. RESULTS: The median survival of our patients was 22
      months. Pain and asthenia were improved in the majority of patients. Every
      patient with baseline elevated liver enzymes showed an improvement in liver
      function. RAR-alpha, RXR-alpha, RAR-beta and RAR-gamma receptors were
      demonstrated in 100%, 73%, 47% and 40%, respectively. CONCLUSION: A combination
      therapy of all-trans retinoic acid, tamoxifen and vitamin E increases the
      survival rate and ameliorates the clinical outcome in patients with inoperable
      HCC.

PMID- 15154657
TI  - Serum levels of HER2 ECD can determine the response rate to low dose oral
      cyclophosphamide and methotrexate in patients with advanced stage breast
      carcinoma.
AB  - BACKGROUND: The proto-oncogene HER2/neu encodes for a transmembrane receptor
      protein whose overexpression in breast cancer may be associated with poor
      prognosis. Its extracellular domain (HER2 ECD) can be shed into the circulation.
      The purpose of this study was to evaluate the predictive value of HER2 ECD in
      patients with advanced breast cancer. PATIENTS AND METHODS: HER2 ECD was
      determined in 39 patients with advanced breast cancer, treated with oral
      cyclophosphamide and methotrexate (CM) at low doses. HER2 ECD levels were
      determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of
      chemotherapy, when all the patients were re-evaluated. RESULTS: Based on the
      response to chemotherapy, the patients were divided into two groups: progressive
      disease (PD, 14 patients) and patients with clinical benefit (CB; i.e. patients
      with stable or responsive disease, 25 patients). The patients with PD had a mean
      baseline value of HER2 ECD of 38.3+/-69.2 ng/ml, while the group of CB showed
      lower levels (9.2+/-2.3 ng/ml, p<0.05). After 2 months, the mean value of HER2
      ECD in the PD group increased to 71.6+/-146 ng/ml, while in the other group the
      levels did not change (9.7+/-2.4 ng/ml). At follow-up, significant differences
      were noted in both the time to progression and overall survival, with patients
      with increased levels of HER2 ECD at baseline (> or = 15 ng/ml) showing a worse
      clinical outcome. CONCLUSION: Increased pretreatment levels of HER2 ECD identify
      a subset of patients with more aggressive tumors and less response to CM
      chemotherapy. During therapy, increasing levels of HER2 ECD are associated with
      disease progression.

PMID- 15154658
TI  - Topotecan as a continuous infusion over 14 days in recurrent ovarian cancer
      patients.
AB  - OBJECTIVE: In recurrent ovarian cancer the topoisomerase-1 inhibitor topotecan
      shows activity after prior treatment with platinum and taxanes. Overall response
      rates of up to 38% in combination with an acceptable toxicity profile have been
      reported. We performed a pilot study to evaluate the therapeutic efficacy and
      toxicity profile of a low-dose continuous infusion protocol of topotecan.
      PATIENTS AND METHODS: Twelve patients with recurrent ovarian cancer and a
      measurable lesion received a continuous infusion of topotecan (0.4 mg/m2/d) over
      14 days, repeated every 28 days. All patients had at least one prior platinum
      containing regimen of chemotherapy (range 1-7). Responses were evaluated by
      ultrasound, computed tomography (CT) scans and/or magnetic resonance imaging
      (MRI). RESULTS: A total of 57 (median 5, range 1-12) topotecan treatment cycles
      were administered. The overall response rate was 2/12 (17%). Four patients had
      stable disease (33%), among them two patients with platinum-refractory tumors.
      The median time to progression was 26 (range 20-100) weeks. No grade 3 or 4
      hematological toxicities were observed. However, one patient developed a grade 2
      allergy leading to discontinuation of topotecan. CONCLUSION: Treatment of
      recurrent ovarian cancer with low-dose continuous infusion of topotecan over 14
      days demonstrated response rates comparable to other dosing schedules with
      minimal toxicity in a preliminary series of 12 patients.

PMID- 15154659
TI  - Serum bone markers in breast cancer patients during 5-fluorouracil, epirubicin
      and cyclophosphamide (FEC) therapy.
AB  - BACKGROUND: Chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide
      (FEC) is now indicated for adjuvant therapy of breast cancer. Its effects on
      serum bone markers and bone metabolism are unclear. PATIENTS AND METHODS: The
      bone formation marker serum osteocalcin, the bone resorption marker serum
      carboxyterminal telopeptide of type I collagen (CTx), serum parathyroid hormone
      (PTH), 25-hydroxyvitamin D (25(OH)D) and calcium concentrations were assessed in
      nine premenopausal breast cancer patients with no distant metastases at baseline,
      before the fourth cycle and after the ninth cycle of FEC therapy. All patients
      became amenorrheic during chemotherapy. RESULTS: Individual values of bone
      markers remained within the reference ranges. The mean concentrations increased
      slightly. The only significant changes from baseline were observed in serum
      osteocalcin; concentrations were 17.6+/-4.9 microg/l (mean+/-SD), 17.5+/-4.2
      microg/l, 22.8+/-6.4 microg/l (p=0.003). Serum CTx concentrations were 998+/-605
      pmol/l, 886+/-562 pmol/l and 1473+/-1102 pmol/l at baseline, before the 4th and
      after the 9th cycle (p=ns). Serum 25(OH)D concentrations were all very low (mean
      concentrations were 26.6+/-10.1 mmol/l, 29.9+/-6.5 mmol/l and 27.7+/-10.6 mmol/l)
      and remained stable as did mean serum PTH and calcium concentrations. CONCLUSION:
      The finding of slight increases of the bone markers suggests early bone loss in
      premenopausal women. The independent effects of estrogen deprivation on bone
      cannot be separated from the effects of FEC therapy on bone.

PMID- 15154660
TI  - Fulvestrant for the treatment of advanced breast cancer in postmenopausal women:
      a Japanese study.
AB  - BACKGROUND: Fulvestrant ('Faslodex') is a new type of oestrogen receptor (ER)
      antagonist that down-regulates the ER and has no known agonist effects. PATIENTS
      AND METHODS: In this open-label, Phase II trial, 30 postmenopausal Japanese women
      with hormone-sensitive advanced breast cancer, who had progressed on
      tamoxifen/toremifene following an initial response, received fulvestrant (250 mg;
      once-monthly intramuscular injection). Primary endpoints were objective tumour
      response rate (complete or partial response) and assessment of tolerability;
      secondary endpoints included clinical benefit (objective response, or stable
      disease > or = 24 weeks), duration of response and pharmacokinetic analysis.
      RESULTS: The objective response rate was 23.3% and 60.0% of patients experienced
      clinical benefit. Adverse events were generally mild; the most common were
      pharyngitis (26.7%), headache (23.3%) and nausea (20.0%). Pharmacokinetic data
      were similar to a Western study of postmenopausal patients. CONCLUSION:
      Fulvestrant 250 mg/month is effective and well-tolerated in Japanese patients who
      have relapsed after one prior endocrine treatment.

PMID- 15154661
TI  - Value of multilevel sectioning for improved detection of micrometastases in
      sentinel lymph nodes in invasive squamous cell carcinoma of the vulva.
AB  - Clinical usefulness of sentinel lymph node (SLN) biopsy has been demonstrated in
      the management of early vulvar cancer. However, what constitutes a negative SLN
      has not been well defined. Furthermore, to what extent the SLNs should be
      sectioned for the greatest likelihood of detection of micrometastases and whether
      multilevel sectioning will further increase this detection rate in this setting
      have not been well studied. We analyzed 280 groin lymph nodes (SLNs=45, non
      sentinel [NSLNs]=235) in 14 patients with invasive squamous cell carcinoma (ISCC)
      of the vulva treated with vulvectomy and inguinal SLN and NSLN dissection at the
      H. Lee Moffitt Cancer Center (HLMCC) between 1996 and 2001. Each SNL was
      evaluated for micrometastases by H&E and pancytokeratin AE1/3 (CKAE1/3)
      immunohistochemical staining. All negative SNLs (N=40) were sectioned times 3
      (x3) at 50-micron intervals and independently reviewed by two pathologists in
      order to assess the utility of this inexpensive and logical approach to
      identifying additional micrometastases. Also, the Wilcoxon Rank Sum Test was used
      to determine if there was an association between tumor size, depth of invasion
      and SNL status. The patient age ranged from 35 to 81 years (mean 59 yrs); size of
      invasive tumor from 1.0 to 7.0 cm (mean 3.4 cm); depth of invasion from 3 to 25
      mm (mean 10.8 mm). Of 45 SLNs examined from 14 patients, 11% (5/45) SNLs were
      positive for micrometastases on initial H&E and/or CKAE1/3 stains. Eighty-nine
      per cent (40/45) SNLs were negative in the remaining 9 patients. None of the
      latter 40 SNLs showed micrometastases on additional multilevel sectioning.
      Instead 3 of 135 NSLNs examined in these 9 patients revealed micrometastases on
      H&E (skip-micrometastases). Mean tumor size (cm) and depth of invasion (cm) were
      4.06 (s.d. 1.89) and 1.20 (s.d. 0.35) for SLN (+) and 3.02 (s.d. 2.12) and 1.01
      (s.d. 0.86) for SLN (-) tumor subsets (p values 0.385 and 0.348, respectively).
      CONCLUSION: Following routine H&E and CK AE1/3 stains, multilevel sectioning does
      not appear to detect additional micrometastases in sentinel lymph nodes in
      squamous cell carcinoma of the vulva. Even though mean tumor size and depth of
      invasion were greater in SNL (+) as compared to SLN (-) tumor subsets in our
      series, this difference did not reach statistical significance.

PMID- 15154662
TI  - Alfa-epoietin and anaemia in gynaecological cancer.
AB  - The incidence and severity of anaemia in gynaecological cancer patients depends
      on several factors including age, histology and tumor stage, site of neoplasm and
      treatment. At present, two principal opinions are available for the management of
      chronic anaemia in cancer patients: blood transfusions and treatment with
      recombinant human Erythropoietin (rHuEPO). Clinical studies showed that rHuEPO
      can ameliorate chronic and chemotherapy-induced anaemia and reduce transfusions
      in patients with various malignant diseases. In this review we discuss the role
      of alfa-epoetin in the management of gynaecological and breast cancers.

PMID- 15154663
TI  - The standardised mistletoe extract PS76A2 improves QoL in patients with breast
      cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled,
      double-blind, multicentre clinical trial.
AB  - Patients with breast cancer receiving adjuvant chemotherapy frequently suffer
      from a restricted quality of life (QoL) due to the side-effects of chemotherapy
      and the consequences of coping with the diagnosis. Therefore, the objective of
      this clinical study was to investigate the impact of PS76A2, an aqueous mistletoe
      extract standardised to the galactoside-specific mistletoe lectin, on QoL by
      performing a placebo-controlled trial. Overall, 272 patients with breast cancer
      receiving adjuvant CMF chemotherapy (cyclophosphamide-methotrexate-fluorouracil)
      were enrolled and randomised to groups receiving placebo or PS76A2 at
      concentrations of 10, 30 or 70 ng mistletoe lectin (ML) per ml. The patients
      received 0.5 ml study medication twice weekly subcutaneously for 15 consecutive
      weeks (4 CMF cycles). Primary variables were the self-assessment QoL scores GLQ-8
      (Global Life Quality) and Spitzer's uniscale. As a result, statistically
      significant effects on QoL were obtained with the medium dose (15 ng ML/0.5 ml).
      The treatment difference between the medium dose and placebo with regard to the
      GLQ-8 sum was 60.8 mm (95% confidence interval: 19.3 to 102.0 mm). The treatment
      effect for Spitzer's uniscale between the medium dose and placebo was 16.4 mm
      (95% confidence interval: 6.3 to 26.6 mm). The results on QoL were supported by
      an increase of T helper lymphocytes (CD4+) and the CD4+/CD8+ ratio (p<0.05).
      Overall, PS76A2 was well tolerated. Local reactions at the injection sites
      occurred dose-dependently, but were mild at the low and medium dose levels.

PMID- 15154664
TI  - Local recurrence in breast cancer after conservative surgery: timing of
      radiotherapy and sequencing of chemotherapy.
AB  - BACKGROUND: A randomized trial was conducted to determine (a) the role of
      radiotherapy and chemotherapy on local control and (b) to determine the timing of
      radiotherapy for early-stage breast cancer. MATERIALS AND METHODS: Five hundred
      and ninety patients were treated with both conservative surgery and radiotherapy
      (group A). The average time interval between surgery and radiation was 90 days
      for 452 patients and over 90 days for 138 patients. One hundred and ninety-four
      patients underwent adjuvant therapy based on CMF regimens (group B). RESULTS:
      Among 396 patients of group A, 8.1% had local failure; we observed 7.2% local
      recurrences in 363 patients who received therapy before 90 days and 18.2% in
      patients who received therapy after 90 days. Among patients of group B, 7.7% had
      local failure; for patients who underwent radiotherapy before 90 days, the local
      recurrence rate was 6.6%, compared with 12.3% for patients who underwent therapy
      more than 90 days after surgery. CONCLUSION: In patients who are eligible to
      receive chemotherapy, it is possible to administer radiotherapy after systemic
      treatment, while in patients who have to be treated with radiotherapy more then
      90 days after breast surgery, chemotherapy can reduce the local failure rate.

PMID- 15154666
TI  - The interleukin-6-174 promoter polymorphism is associated with a risk of
      development of Kaposi's sarcoma in renal transplant recipients.
AB  - BACKGROUND: Kaposi's sarcoma (KS), an angio-proliferative inflammation lesion, is
      frequently secondary to clinical immunosuppression such as after renal
      transplantation. KS growth is promoted by the inflammatory cytokine interleukin-6
      (IL-6) and is also correlated with human herpesvirus-8 (HHV-8) infection.
      MATERIALS AND METHODS: In a sample of 15 renal transplant patients with KS and 40
      patients without KS, we explored the influence of genetic differences in the
      production of IL-6 by promoter polymorphisms G-174C as well as the correlation
      with HHV-8 DNA. RESULTS: The G allele homozygotes, which are associated with
      increased IL-6 production, had increased KS incidence (p=0.008). Therefore
      increased IL-6 production constitutes a risk factor which should be considered in
      clinical immunosuppression. CONCLUSION: In addition to the HHV-8 infection, the
      interleukin-6 promoter polymorphism G-174C is associated with a risk of
      development of KS in renal transplant recipients.

PMID- 15154665
TI  - Amphiregulin and epidermal growth factor receptor expression in human malignant
      fibrous histiocytoma of soft tissues.
AB  - BACKGROUND: Amphiregulin is a member of the epidermal growth factor (EGF) system
      and a potent mitogen for various epithelial tissues. Little information, however,
      is currently available on the amphiregulin and EGF receptor (EGF-R) expression in
      mesenchymal malignancies of a fibrohistiocytic origin including malignant fibrous
      histiocytoma (MFH). MATERIALS AND METHODS: We investigated the amphiregulin and
      EGF-R expression in 43 human MFH tissues using immunohistochemical techniques.
      Furthermore, the correlation of the ligand and the receptor expression with tumor
      proliferative activity assessed by MIB-1 indices was analyzed. RESULTS: Positive
      immunoreactivity for amphiregulin and EGF-R was identified in 34 (79%) and 36
      (84%) of the 43 MFH cases analyzed, respectively. Coexpression of amphiregulin
      and EGF-R was observed in 30 (70%) of the 43 MFHs analyzed. There were no
      significant differences in MIB-1 indices between both the amphiregulin and EGF-R
      positive MFHs and the remaining MFHs. CONCLUSION: These results show that
      amphiregulin is expressed not only by epithelial tumor cells but also by MFH
      cells. Our data provide evidence indicating the presence of an autocrine
      mechanism of proliferation control involving the amphiregulin/EGF-R signaling
      system in human MFHs.

PMID- 15154667
TI  - Anastrozole as neoadjuvant therapy for patients with hormone-dependent, locally
      advanced breast cancer.
AB  - BACKGROUND: We investigated the efficacy and safety of anastrozole as neoadjuvant
      therapy in a group of postmenopausal patients with locally-advanced breast
      cancer. PATIENTS AND METHODS: This was an open-label trial, which recruited
      patients with histopathologically-confirmed unilateral, locally-advanced,
      estrogen-receptor-positive breast cancer (stage IIIA/B). All patients received
      anastrozole 1 mg/day for 3 months, after which the clinical response was
      evaluated. All patients with a complete or partial clinical response (cCR or cPR)
      underwent surgery (radical modified mastectomy), after which patients continued
      with the same therapy for two years or until progression. Primary end points were
      clinical response rate (cCR + cPR), surgery rate, pathological complete response
      rate and tolerability profile. RESULTS: cCR and cPR were seen in 61/112 (54.5%)
      and 32/112 (28.6%) patients (n=112), respectively, giving an objective response
      rate of 93/112 (83%) patients. Following surgery in responding patients, 14/61
      patients (23%) had a pathological CR and 47/61 (77%) patients had a pathological
      PR. CONCLUSION: Neoadjuvant anastrozole treatment was highly effective and well
      tolerated in postmenopausal women with hormone-dependent locally-advanced breast
      cancer.

PMID- 15154668
TI  - Human papillomavirus DNA and protein in tissue samples of oesophageal cancer,
      Barrett's oesophagus and oesophagitis.
AB  - BACKGROUND: The risk of presenting with oesophageal cancer is associated with
      Barrett's oesophagus, with a higher prevalence in some Asian and African
      countries. Human papillomavirus (HPV) DNA has been identified in oesophageal
      carcinomas, which share common features with cervical cancers and originate in
      stratified epithelium. MATERIALS AND METHODS: Sixty-eight paraffin-embedded
      tissue biopsies were selected from Mexican patients: 17 from oesophageal cancers,
      28 from cases of Barrett's oesophagus and 23 from cases of oesophagitis. HPV
      protein was detected immunohistochemically and the presence and types of HPV DNA
      were assessed by polymerase chain reaction. RESULTS: HPV DNA-positive results
      were found in 26% of samples of oesophagitis, 96% of samples of Barrett's
      oesophagus and 88% of samples of oesophageal cancers. HPV viral types 6 and 11
      were prevalent. HPV protein was detected in 41 samples (60%). CONCLUSION: Mexico
      has a high prevalence of HPV in premalignant and malignant oesophageal diseases
      compared with other countries.

PMID- 15154669
TI  - 5-Hydroxytryptamine 1B receptors mediate presynaptic inhibition of monosynaptic
      IPSC in the rat dorsolateral septal nucleus.
AB  - Effects of 5-hydroxytryptamine (5-HT) on inhibitory synaptic transmission in the
      rat dorsolateral septal nucleus (DLSN) were examined by conventional
      intracellular and voltage-clamp recording methods. 5-HT (1-30 microM) depressed
      the monosynaptic fast IPSC evoked by local stimulation of the DLSN in the
      presence of DNQX, AP5 and CGP 55845A. CP 93129, a selective 5-HT1B receptor
      agonist, depressed the fast IPSC. The 5-HT-induced depression of the fast IPSC
      was attenuated by SB 216641, a selective antagonist for 5-HT1B receptors. 5-HT
      did not change the inward currents mediated by GABAA receptors, suggesting that 5
      HT presynaptically inhibited the fast IPSC. 5-HT and CP 93129 depressed the
      frequency of miniature fast IPSPs (mIPSPs) without changing their amplitudes.
      Neither a selective protein kinase A inhibitor, H-89, nor a selective protein
      kinase C inhibitor, calphostin C, blocked the 5-HT-induced depression of the fast
      IPSC. N-Ethylmaleimide (NEM) blocked the 5-HT-induced depression of the evoked
      IPSC. These results suggest that activation of presynaptic 5-HT1B receptors
      depresses the release of GABA via a pertussis toxin (PTX)-sensitive G-protein in
      the rat DLSN.

PMID- 15154670
TI  - Sensorial organisation favouring higher visual contribution is a risk factor of
      falls in an occupational setting.
AB  - The contribution of intrinsic balance control factors to fall mechanisms has
      received little investigation in studies on occupational accidents. The aim of
      this study was to assess whether postural regulation in falling workers might
      have specificities in terms of sensorimotor strategies and neuromuscular
      responses to balance perturbations. Nine multi-fall-victims (MF), 43 single-fall
      victims (SF) and 52 controls (C) were compared on performance measurements of
      static and dynamic postural control. MF and SF had the worst postural performance
      both in the static and slow dynamic tests, particularly in eyes closed
      conditions, suggesting a high dependency on visual cues and a lower use of
      proprioception. Moreover, the sensorial analysis showed that MF and SF relied
      less on vestibular input in the development of balance strategy and had more
      difficulties in maintaining a correct upright stance when proprioceptive input
      was altered. Finally, MF showed longer latency responses to unexpected external
      disturbance. Overall, postural control quality increased in the order MF, SF and
      C. MF and SF adopted particular sensorimotor organisation, placing them at an
      increased risk of falling in specific sensory environments. Strategies
      incorporating visual information involve using the cognitive processes causing
      delayed and less accurate fall avoidance responses, in contrast to adaptative
      strategies based on proprioceptive and vestibular information.

PMID- 15154672
TI  - Exposure to hexanal odor influences maternal behavior and induces neonatal death
      in Fyn tyrosine kinase-deficient mice.
AB  - Fyn-deficient pups born of Fyn-deficient parents die because they fail to suckle
      within 1-2 days after birth. Here we demonstrate that the neonatal death
      phenotype was influenced by the genetic background and an environmental odor. The
      odor of hexanal (C6-aldehyde) partially impaired mouse maternal behavior and
      induced the neonatal death of Fyn-deficient pups born of Fyn-deficient parents.
      This death phenotype was first observed in the breeding environment using
      autoclaved chips of Douglas fir. An analysis of the volatile chemicals in the
      autoclaved chips revealed an approximately 10-fold greater amount of hexanal than
      in non-autoclaved chips. Hexanal influenced the length of time virgin female mice
      engage in the maternal crouching behavior. In addition, Fyn-deficient females
      exhibited defects in the maternal behavior of nest building and pup retrieval,
      regardless of exposure to hexanal. These observations provide new insights into
      the regulation of maternal behavior by environmental and genetic factors.

PMID- 15154671
TI  - Localization of SNARE proteins and secretory organelle proteins in astrocytes in
      vitro and in situ.
AB  - Astrocytes are capable of regulated release of messenger molecules. Astrocytes
      cultured from new born rodent brain express a variety of classical presynaptic
      proteins. We investigated the question whether the capability to express synaptic
      proteins in culture was a feature only of immature astrocytes, and whether these
      proteins were also expressed by astrocytes in situ. Experiments were performed
      with transgenic mice expressing the enhanced green fluorescent protein under the
      control of the human glial fibrillary acidic protein promoter. Using double
      fluorescence and astrocytes cultured from 1 to 16 day-old animals we show that
      the astrocytic expression of synaptic proteins in culture is invariant of the age
      of donor animals. Culturing can induce the astrocytic expression of specific
      synaptic proteins such as SV2, synaptophysin and SNAP-25. Astrocytes in brain
      sections of 1-16 day-old animals revealed a punctuate immunofluorescence for
      secretory carrier membrane protein (SCAMP), SNAP-23, synaptobrevin II, and
      cellubrevin, to a minor extent for SNAP-25 and synaptophysin, and none for SV2.
      Our results demonstrate that cultured astrocytes express synaptic proteins not
      present in situ. Nevertheless, astrocytic organelles in situ are equipped with
      molecules that could be involved in regulated exocytosis of messenger substances.

PMID- 15154673
TI  - Effect of side-down tilt on optokinetic nystagmus and optokinetic after-nystagmus
      in cats.
AB  - Slow phase velocity (SPV) of optokinetic nystagmus (OKN) and after-nystagmus
      (OKAN) was examined in the cat in side-down tilts. In the upright position, the
      axis of SPV (direction of SPV vector) during OKN was always close to the stimulus
      axis. In side-down positions, yaw stimulation induced OKN with the vector
      deviating from the stimulus axis toward the pitch-axis, so as to make the SPV
      rotational plane be shifted toward the earth horizontal plane, while pitch-axis
      stimulation induced no change in vector direction. This yaw-to-pitch cross
      coupling is qualitatively similar to that previously described in primates. SPV
      vector size during yaw stimulation is greatest when the stimulus axis is oriented
      vertically, and the vector size is smaller when the stimulus is in the gravity
      direction than when it is in the anti-gravity direction. The SPV vector for the
      rapid-rise response showed no clear change with head orientation, indicating that
      the direct optokinetic pathway has no contribution to the induction of cross
      coupling. Cross-coupling was found also during OKAN. The SPV trajectories were
      fitted well using the velocity storage integrator model. SPV vector change of cat
      OKN/OKAN in head tilt could be fitted by changing gain elements in the model.

PMID- 15154674
TI  - EphA receptor tyrosine kinases interact with co-expressed ephrin-A ligands in
      cis.
AB  - Eph receptor tyrosine kinases have been implicated in various developmental
      processes, including axonal guidance, angiogenesis and morphogenesis. In general,
      Eph receptors and their ligands, ephrins, are reciprocally compartmentalized
      during embryogenesis. However, they are expressed in an overlapping fashion in
      some developing neural and non-neural tissues. Results from the overexpression or
      mutant mice of ephrin ligands in the retino-tectal system suggest that ephrin-As
      regulate co-expressed EphA receptor activity, but little is known about the
      molecular mechanisms. Here we show that EphA receptors and co-expressed ephrin-A
      ligands interact directly in cis via their functional binding domains, and that
      this interaction does not seem to mediate intracellular signals, but has an
      inhibitory effect on the trans interaction.

PMID- 15154675
TI  - Differential contribution of left and right prefrontal cortex to associative cued
      recall memory: a parametric PET study.
AB  - Several brain imaging studies have implicated prefrontal regions bilaterally
      during cued-recall memory tasks and yet the functional significance of these
      regions remains poorly understood. Using PET, we examined the neural activity in
      prefrontal regions of 15 subjects while they performed three cued-recall tasks
      differing in pre-experimental semantic associations between cues and targets.
      This manipulation produced varying levels of retrieval performance when one
      member (a semantic category name) of the triad was used as a cue for the
      retrieval of the other two members. The percentage of items correctly recalled
      was 10, 46, and 70 in the low, medium, and high cued-recall conditions,
      respectively. Linear contrast analyses of the PET data identified brain regions
      where neural activity varied with the number of items retrieved from memory. A
      left lateral prefrontal region showed maximal activity during the high cued
      recall condition, which likely reflects processes involved in retrieval success
      and possibly in the generation of memory responses. Three right prefrontal
      regions (anterior and dorsolateral) showed maximal activity during the low cued
      recall condition, which likely reflects processes involved in memory
      search/monitoring. These findings add further support for a bilateral prefrontal
      contribution to memory cued-recall tasks and point to differential roles of the
      two hemispheres.

PMID- 15154676
TI  - Vesicular acetylcholine transporter can be a morphological marker for the
      reinnervation to muscle of regenerating motor axons.
AB  - This study was designed to evaluate whether the vesicular acetylcholine
      transporter (VAChT), which packages acetylcholine into synaptic vesicles, can be
      used as a marker for regenerating motor axon terminal. We examined motor axon
      regeneration in the tongue after hypoglossal nerve axotomy, using an anterograde
      tracer biotin-dextran (BD), retrograde tracer Fluoro-Gold (FG), electron
      microscopic (EM) observation, and VAChT immunocytochemistry. BD study
      demonstrated that outgrowth of thin regenerating axons into the frontal area of
      the tongue was firstly observed at 14 post-operative days, and presynaptic
      formation of neuromuscular junction (NMJ) was observed from 21 post-operative
      days. Under electron microscopic observation, reconstruction of new NMJs was
      observed within the interval between 21 and 28 days. VAChT-immunoreactive nerve
      terminals disappeared by 3 days after axotomy, slightly appeared at 14 post
      operative days, and thereafter gradually increased in number from 21 to 28 post
      operative days. The re-expression of VAChT positive presynaptic terminal was
      almost the same as those obtained in BD, FG and EM studies. Regenerating axons
      tip in the crush model of the hypoglossal nerve exhibited prominent VAChT
      immunoreactivity in growing tip of regenerating axons. These indicate that VAChT
      is an excellent morphological indicator for regenerating nerve terminals of motor
      neurons.

PMID- 15154677
TI  - Effects of beta-AP peptides on activation of the transcription factor NF-kappaB
      and in cell proliferation in glial cell cultures.
AB  - The effect of two beta amyloid peptides (Abeta 25/35 and Abeta 1/42) on the
      activation of the transcription factor kappaB (NF-kappaB) in pure astroglial,
      pure microglial and mixed glial cell cultures was compared by means of single or
      double immunofluorescence and Western blot techniques. We also studied the effect
      of both peptides in cell proliferation in mixed glial cultures and pure
      astrocytes. The Abeta 1/42 peptide induced the activation of NF-kappaB in all
      studied cell cultures and its effect was potentiated by interferon-gamma (IFN
      gamma). Abeta 25/35 alone did not induce NF-kappaB activation, but Abeta 25/35
      plus IFN-gamma induced the activation of the transcription factor in the mixed
      and pure microglial cultures, although not in pure astroglia. The Abeta 1/42
      peptide, but not Abeta 25/35, induced proliferation in pure astroglial and mixed
      glial cell cultures. The results suggest that the state of peptide aggregation is
      related to their ability to activate glial cells.

PMID- 15154678
TI  - NMDA receptor-mediated depolarizing after-potentials in the basal dendrites of
      CA1 pyramidal neurons.
AB  - It was shown recently that the basal dendrites of cortical pyramidal neurons
      generate NMDA-spikes. In the present study, we made whole-cell recordings from
      hippocampal CA1 pyramidal neurons and examined whether NMDA receptor activation
      was involved in synaptic responses. At low input stimulus intensity, EPSPs with a
      fast decay time were induced. As the intensity of stimulation was increased in
      the presence of GABA receptor antagonists, a depolarizing after-potential (DAP)
      was generated in addition to a fast decaying potential. A DAP was never observed
      when the input was applied to the apical dendrites. The DAP was suppressed by
      hyperpolarization or by NMDA receptor antagonists, but not by Na+, K+, or Ca2+
      channel blockers. One possible mechanism is that the morphology of the basal
      dendrites favors DAP generation. A compartmental model simulation showed that
      synaptic inputs to thinner shorter dendrites generated a potential that resembled
      a DAP. Our study shows that a synaptic input to the basal dendrites of a
      hippocampal pyramidal neuron can generate a NMDA receptor-mediated potential in
      the presence of GABA receptor blockade.

PMID- 15154679
TI  - The inhibitory role of methylation on the binding characteristics of dopamine
      receptors and transporter.
AB  - Excess methylation has been suggested to play a role in the pathogenesis of
      Parkinson's disease (PD), since the administration of S-adenosylmethionine (SAM),
      a biological methyl donor, induces PD-like changes in rodents. It was proposed
      that SAM-induced PD-like changes might be associated with its ability to react
      with the dopaminergic system. In the present study the effects of SAM on dopamine
      receptors and transporters were investigated using rats and cloned dopamine
      receptor proteins. Autoradiographic examination of SAM indicated its tendency to
      be localized and accumulated in rat striatal region after the
      intracerebroventricular injection into rat brain. Moreover, results showed that
      SAM significantly decreased dopamine D1 and D2 receptor binding activities by
      decreasing the Bmax and increasing the Kd values. At concentrations of 0.1, 0.25
      and 0.5 mM, SAM was able to reduce the Bmax from the control value of 848.1 for
      dopamine D1-specific ligand [3H] SCH 23390 to 760.1, 702.6 and 443.0 fmol/mg
      protein, respectively. At the same concentrations, SAM was able to increase the
      Kd values from 0.91 for the control to 1.06, 3.84 and 7.01 nM of [3H] SCH 23390,
      respectively. The effects of SAM on dopamine D2 binding were similar to those of
      dopamine D1 binding. SAM also decreased dopamine transporter activity. The
      interaction of SAM with dopamine receptor proteins produced methanol from methyl
      ester formation and hydrolysis. We propose that the SAM effect might be related
      to its ability to react with dopamine receptor proteins through methyl-ester
      formation and methanol production following the hydrolysis of the carboxyl
      methylated receptor proteins.

PMID- 15154681
TI  - Simulation of alternatives for the Dutch Johne's disease certification-and
      monitoring program.
AB  - To identify optimal method(s) for certification and subsequent monitoring of
      Mycobacterium avium subsp. paratuberculosis (Map)-unsuspected herds,
      certification-and-monitoring schemes were studied using a stochastic simulation
      model ("JohneSSim"). JohneSSim simulated the within-herd transmission and
      economic aspects of Map in closed Dutch dairy herds. The model was validated with
      field observations on Map-unsuspected herds. The current Dutch certification-and
      monitoring schemes were compared with 11 alternative schemes in which individual
      and pooled fecal culture, ELISA, Johnin-intradermal test and gamma-IFN ELISA were
      used, varying the test frequency, tested age group and number of tested animals.
      On reaching the 'Map-free' status with the standard certification scheme, 11% of
      the simulated herds were not truly Map-free. Therefore, the designation 'Map
      free' should be changed into, for instance, 'low-risk Map'. In the most
      attractive alternative certification scheme, the 'Map-free' status was reached
      after four herd examinations (at 2-year intervals) consisting of serial testing
      of all cattle > or = 2 years of age with a pooled fecal culture and individual
      fecal culture of positive pools. This scheme resulted in lower total and annual
      discounted costs and a lower animal-level prevalence at reaching the 'Map-free'
      status compared to the standard scheme, assuming that there was no new
      introduction of the infection. Schemes to monitor the 'Map-free' status were
      compared, assuming that this status was reached with the standard certification
      scheme. In comparison to the standard monitoring scheme, none of the alternative
      monitoring schemes resulted in both a lower animal-level prevalence of undetected
      pre-existing Map infections in closed herds, and lower median annual discounted
      costs. Results of the model were very sensitive to the assumed sensitivity of the
      fecal culture test and to management measures that prevent within-herd
      transmission of Map. If these preventive measures were taken, the probability of
      undetected Map infections in closed 'Map-free' herds was decreased substantially.

PMID- 15154680
TI  - Neonatal impact of leukemia inhibitory factor on neurobehavioral development in
      rats.
AB  - Cytokines have been implicated in the etiology or pathology of various
      psychiatric diseases of developmental origin such as autism and schizophrenia.
      Leukemia inhibitory factor (LIF) is induced by a variety of brain insults and
      known to have many influences on mature and immature nervous system. Here, we
      assessed the neurobehavioral and pathological consequences of peripheral
      administration of LIF in newborn rats. Subcutaneous LIF injection induced STAT3
      phosphorylation in many brain regions and increased glial fibrillary acidic
      protein (GFAP) immunoreactivity in the neocortex, suggesting that LIF had direct
      effects in the central nervous system. The LIF-treated rats displayed decreased
      motor activity during juvenile stages, and developed abnormal prepulse inhibition
      in the acoustic startle test during and after adolescence. They displayed normal
      learning ability in active avoidance test, however. Brain neuronal structures and
      startle responses were grossly normal, except for the cortical astrogliosis
      during neonatal LIF administration. These results indicate that LIF induction in
      the periphery of the infant has a significant, but discrete impact on
      neurobehavioral development.

PMID- 15154682
TI  - Mortality (including euthanasia) among Danish dairy cows (1990-2001).
AB  - Mortality among Danish dairy cows was examined using data from the Danish Cattle
      Database (DCD) and a questionnaire survey. Mortality risk has increased from
      approximately 2% in 1990 to approximately 3.5% in 1999. The increased mortality
      was seen for all dairy breeds and all age groups. Mortality among older dairy
      cows (parity 3 and older) was approximately twice the mortality among younger
      cows. 30-40% of deaths were during the first 30 days of the lactation.
      Approximately, 58% of dead dairy cows had been euthanised. Replies from the
      questionnaire indicate that the proportion of euthanised cows has increased in
      the past 5 years. In 86% of all deaths (questionnaire survey) a primary reason
      could be identified; 25% were for locomotor disorders.

PMID- 15154683
TI  - Risk factors for the presence of Campylobacter spp. in Dutch broiler flocks.
AB  - The campylobacter status of 495 broiler flocks sampled in The Netherlands between
      April 1997 and December 2000 was related to farm- and flock-specific information
      obtained from questionnaires to identify potential risk factors for campylobacter
      presence. Approximately 30% of the flocks tested positive for Campylobacter spp.
      in at least one pooled faecal sample. Multivariable logistic regression showed
      significant risk increments for: ages 29-35 days (OR = 2.34) and 36-42 days (OR =
      3.96) compared to 22-28 days; > or =5 broiler houses on the premises (OR = 3.02);
      the presence of other farm animals on the farm (OR = 1.88); the presence of
      animals on farms within 1 km (OR = 9.56); and summer (OR = 3.48) and fall (OR =
      2.59) compared to winter. Furthermore, hatcheries differed (ORs from 5.42 to
      20.2), although this variable showed strong collinearity with the variables
      explaining feed mill and integrated poultry operations. We also identified
      interaction in which an increased risk from children entering the broiler house
      (OR = 28.0) was diminished by the use of broiler-specific workclothes. Population
      attributable fractions (PAFs) suggested that animals on farms within 1 km (PAF =
      0.76) and hatchery (PAF = 0.67) had the highest impacts on campylobacter presence
      in Dutch broiler flocks. These factors, however, lack an easy interpretation of
      the mechanism behind the suggested effect.

PMID- 15154684
TI  - Simulated hazards of loosing infection-free status in a Dutch BHV1 model.
AB  - A compulsory eradication programme for bovine herpesvirus 1 (BHV1) was
      implemented in the Netherlands in 1998. At the start of the programme, about 25%
      of the dairy herds were certified BHV1-free. Simulation models have played an
      important role in the decision-making process associated with BHV1 eradication.
      Our objective in this study was to improve understanding of model behaviour (as
      part of internal validation) regarding loss by herds of the BHV1-free
      certificate. Using a Cox proportional hazards model, the association between farm
      characteristics and the risk of certificate loss during simulation was
      quantified. The overall fraction of herds experiencing certificate loss amongst
      initially certified during simulation was 3.0% in 6.5 years. Factors that
      increased risk for earlier certificate loss in the final multivariable Cox model
      were higher 'yearly number of cattle purchased', 'farm density within a 1 km
      radius' and 'cattle density within a 1 km radius'. Qualitative behaviour of risk
      factors we found agreed with observations in field studies.

PMID- 15154685
TI  - What has happened in norway after the ban of avoparcin? Consumption of
      antimicrobials by poultry.
AB  - When avoparcin was prohibited for use as feed additive in poultry in Norway on 31
      May 1995, an increased incidence of Clostridium perfringens-associated necrotic
      enteritis (NE) and an increase in the use of antibacterial (AB) drug therapy in
      meat-type poultry was expected. The consumption of AB drugs for use against NE in
      poultry in the period 1990-2001 was investigated by use of sales statistics at
      the drug-wholesaler level. Defined daily dose (DDD) per kg live weight poultry
      was the unit of measurement for drug use (to correct for differences in the
      dosages). Sales figures of the AB drugs were converted to number of DDDpoultry
      sold for the numbers of broilers at risk (broilers were 97% of the slaughter
      poultry). Estimated annual percentages of the broilers treated against NE
      increased abruptly after the avoparcin ban--but in 1996, this figure declined to
      the same level as before the ban and has remained at that low level since then.
      In November 1995, narasin was approved temporarily as an ionophore feed additive
      (IFA) in broilers. The usage patterns of IFAs in broilers were measured as the
      weight of feed to which an IFA was added per broiler chicken produced. In 1996
      2001, the IFAs used in broilers were predominantly narasin. We note that the
      temporary increase in NE after the avoparcin ban coincide with the period before
      narasin became available. The increase in the consumption of AB drugs for the
      treatment of NE in poultry following the avoparcin ban has been negligible.

PMID- 15154686
TI  - The interaction of partial public insurance programs and residual private
      insurance markets: evidence from the US Medicare program.
AB  - A ubiquitous form of government intervention in insurance markets is to provide
      compulsory, but partial, public insurance coverage and to allow voluntary
      purchases of supplementary private insurance. This paper investigates the effects
      of such programs on insurance coverage for the risks not covered by the public
      program, using the example of the US Medicare program. I find that Medicare does
      not have substantial effects-in either direction-on coverage in residual private
      insurance markets. In particular, there is no evidence that Medicare is
      associated with reductions in private insurance coverage for prescription drug
      expenditures, an expenditure risk not covered by Medicare. Medicare is, however,
      associated with a shift in the source of prescription drug coverage, from
      employer-provided coverage to Medicare HMOs.

PMID- 15154687
TI  - Accidents will happen? Unintentional childhood injuries and the effects of child
      care regulations.
AB  - Accidents are the leading cause of death and injury among children in the United
      States, far surpassing diseases as a health threat. We examine the effects of
      child care regulation on rates of accidental injury using both micro data from
      the National Longitudinal Survey of Youth, and Vital Statistics mortality
      records. Estimates from both data sources suggest that requiring day care center
      directors to have more education reduces the incidence of unintentional injuries.
      An auxiliary analysis of the choice of child care mode confirms that these
      regulations are binding and that higher educational requirements tend to crowd
      some children out of care, as do regulations requiring frequent inspections of
      child care facilities and lower pupil-teacher ratios. Thus, regulation creates
      winners and losers: Some children benefit from safer environments, while those
      who are squeezed out of the regulated sector are placed at higher risk of injury.

PMID- 15154688
TI  - How do Zero Tolerance Drunk Driving Laws work?
AB  - This paper provides the first comprehensive analysis of the effects of "Zero
      Tolerance" (ZT) Drunk Driving Laws--which set very low legal blood alcohol limits
      for individuals under age 21--on self-reported alcohol use and drunk driving
      using data from the 1984 to 2001 Behavioral Risk Factor Surveillance System
      (BRFSS). I estimate two-way fixed effects models of alcohol-related behaviors of
      18-20-year-olds that can condition on unobserved differences across states that
      may be correlated with determinants of drinking and drunk driving, and I use 22
      24-year-olds as a control group. Results indicate that the laws reduced heavy
      episodic drinking (five or more drinks at one sitting) among underage males by
      13%. This result is supported by models that use variation in treatment intensity
      induced by differences in body weight. I find mixed evidence of ZT effects for
      females, and no robust effects on drinking participation or drunk driving for
      either sex.

PMID- 15154689
TI  - An optimal contract approach to hospital financing.
AB  - Existing models of hospital financing advocate mixed schemes which include both
      lump-sum and cost-based payments. The doctor is generally the unique decision
      maker, which is unrealistic in a hospital setting where both managers and doctors
      are involved. This paper develops a model in which managers and doctors are
      responsible for different decisions within the hospital. In this model, public
      authorities who provide the financing, hospital managers who allocate resources
      within the hospital, and doctors who assign patients to either a low-tech or a
      high-tech therapy have information of increasing quality on the casemix of
      patients. The public authorities sign with hospital managers contracts specifying
      some lump-sum financing and some size of a high-tech equipment. In turn,
      managers, who know the broad mix of patients in the hospital, sign with hospital
      doctors contracts that specify the non-medical resources allocated to this
      facility as well as some remuneration. Doctors, who know each patient's illness
      severity, select the patients to be treated by the high-tech facility, and
      receive from public authorities some fee-for-service payment that is
      differentiated according to the low- or high-tech treatment used for curing their
      patients. What emerges is a two-stage agency problem in which contracts are
      designed to elicit information in the most efficient way.

PMID- 15154691
TI  - Effect of drive-through delivery laws on postpartum length of stay and hospital
      charges.
AB  - Postpartum hospital length of stay fell rapidly during the 1980s and 1990s,
      perhaps due to increased managed care penetration. In response, 32 states enacted
      early postpartum discharge laws between 1995 and 1997, and a federal law took
      effect in 1998. We analyze how these laws changed length of stay and hospital
      charges, using a national discharge database. Difference-in-differences models
      show that the laws increased both length of stay and hospital charges, but the
      magnitude of this effect is much smaller than has been estimated in previously
      reported case studies. Furthermore, we find that effects vary by law details,
      that ERISA diluted the law effects, and that law effects partially spilled over
      to unregulated Medicaid births.

PMID- 15154690
TI  - Advance directives and medical treatment at the end of life.
AB  - To assess the consequences of advance medical directives--which explicitly
      specify a patient's preferences for one or more specific types of medical
      treatment in the event of a loss of competence--we analyze the medical care of
      elderly Medicare beneficiaries who died between 1985 and 1995. We compare the
      care of patients from states that adopted laws enhancing incentives for
      compliance with advance directives and laws requiring the appointment of a health
      care surrogate in the absence of an advance directive to the care of patients
      from states that did not. We report three key findings. First, laws enhancing
      incentives for compliance significantly reduce the probability of dying in an
      acute care hospital. Second, laws requiring the appointment of a surrogate
      significantly increase the probability of receiving acute care in the last month
      of life, but decrease the probability of receiving nonacute care. Third, neither
      type of law leads to any savings in medical expenditures.

PMID- 15154692
TI  - Equity weights in the allocation of health care: the rank-dependent QALY model.
AB  - This paper introduces the rank-dependent quality-adjusted life-years (QALY)
      model, a new method to aggregate QALYs in economic evaluations of health care.
      The rank-dependent QALY model permits the formalization of influential concepts
      of equity in the allocation of health care, such as the fair innings approach,
      and it includes as special cases many of the social welfare functions that have
      been proposed in the literature. An important advantage of the rank-dependent
      QALY model is that it offers a straightforward procedure to estimate equity
      weights for QALYs. We characterize the rank-dependent QALY model and argue that
      its central condition has normative appeal.

PMID- 15154693
TI  - Is cigarette smoking in poorer nations highly sensitive to price? Evidence from
      Russia and China.
AB  - We examine cigarette demand in China and Russia using longitudinal micro-level
      household and community surveys. Previous developing-country price elasticity
      estimates of around -0.75 have been larger than United States estimates of about 
      0.4, but the former have relied primarily on aggregate data. In contrast, our
      micro-level price elasticity estimates in China and Russia range from 0 to -0.15.
      Thus, raising prices in poorer countries may not reduce smoking to the degree
      previously suggested.

PMID- 15154694
TI  - Within-year variation in hospital utilization and its implications for hospital
      costs.
AB  - Variability in demand for hospital services may have important effects on
      hospital costs, but this has been difficult to examine because data on within
      year variations in hospital use have not been available for large samples of
      hospitals. We measure daily occupancy in California hospitals and examine
      variation in hospital utilization at the daily level. We find substantial day-to
      day variation in hospital utilization, and noticeable differences between
      hospitals in the amount of day-to-day variation in utilization. We examine the
      impact of variation on hospital costs, showing that increases in variance are
      associated with increases in hospital expenditures, but that the effects are
      qualitatively modest.

PMID- 15154695
TI  - Assessing the quality of image reporting.

PMID- 15154696
TI  - Clinical audit in nuclear medicine.
AB  - BACKGROUND AND AIM: Clinical governance is important. Clinical audit is part of
      clinical governance. The aim of this study was to perform a clinical governance
      exercise, and the reporting arrangements at an independent hospital provided the
      opportunity to do this over two phases between 1999 and 2002. Six physicians from
      four different UK National Health Service (NHS) trusts participated. METHODS:
      Reports were shown anonymously to between two and five of the physicians who had
      not produced the report. Reports with at least one disagreement were reviewed by
      the group in order to reach concensus as to whether the disagreement was non
      sustainable (NS), trivial (T) or non-trivial (NT), the last two, respectively,
      judged to make an insignificant or potentially significant impact on patient
      management. RESULTS: In phase 1,239 audits were produced on 83 reports (2.9 per
      report), and in phase 2, 636 on 137 reports (4.6 per report). In phase 1, 14
      (17%) reports attracted at least one disagreement (NS, five; T, four; NT, five).
      Of 239 audits, there were 20 disagreements of which five were NS. Moreover, nine
      audits agreed with a report with a NT disagreement, giving 14 suboptimal audits
      (5.9%). In phase 2, 80 (58%) reports attracted at least one disagreement (NS, 31
      (P<0.003 vs phase 1); T, 35 (P<0.001); NT, 14 (P>0.05)). Of 636 audits, there
      were 153 disagreements, of which 37 were NS (P<0.05 vs phase 1). Twenty-five
      audits agreed with a report with a NT disagreement, giving 62 suboptimal audits
      (9.7%) (P>0.05). Overall, 19/220 reports (8.6%) were thought NT, an error rate
      comparable to reporting elsewhere in radiology. After phase 1, auditors became
      more aggressive but the quality of auditing tended to decline, as did the quality
      of reporting (although not significantly). CONCLUSION: This study provides a
      useful framework for monitoring performance.

PMID- 15154697
TI  - Detection of recurrent colorectal carcinoma by 18F-FDG: comparison of the
      clinical performances of FDG PET and FDG CDET.
AB  - OBJECTIVES: To assess the clinical performance of fluorodeoxyglucose positron
      emission tomography (FDG PET) using either a coincidence (CDET) gamma camera or
      PET equipment with Nal crystals for the detection of recurrences of colorectal
      cancer. METHODS: From July 1997 to December 1999, 290 examinations were performed
      in 244 patients using a CDET gamma camera (2-dimensional system with 19 mm thick
      crystals). Additionally, from January 2000 to July 2002, 354 examinations were
      performed in 303 patients using PET (3-dimensional system with Nal crystals).
      RESULTS: Four hundred and seventy-three of the 644 examinations performed were
      evaluable on the basis of histological data (202 examinations) or more than 6
      months of follow-up (273 examinations). The performances of the two systems were
      equivalent on a patient basis (sensitivity, specificity and accuracy of dedicated
      PET was 92%, 84% and 90%, respectively; and sensitivity, specificity and accuracy
      of CDET was 90%, 94% and 91%, respectively). On a site basis, a highly
      significant reduction in sensitivity was observed for lesions < or = 10 mm vs. >
      10 mm with both PET and the CDET gamma camera, but no difference was observed
      between PET and CDET according to the size of the lesions. CONCLUSION: For
      detection of recurrent colorectal carcinoma, a 2-D coincidence gamma camera with
      19 mm thick crystals and optimized acquisition and reconstruction parameters
      provides similar results in terms of accuracy, both per patient and per site, to
      those of an Nal PET camera.

PMID- 15154698
TI  - Elevated 18F-FDG uptake in skeletal muscles and thymus: a clue for the diagnosis
      of Graves' disease.
AB  - AIM: The aim of this study was to evaluate the appearance of Graves' disease in
      whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography
      (PET) imaging. SUBJECTS: Twenty patients (three men, 17 women; mean age +/- SD,
      37.2 +/- 12.1 years) with newly diagnosed Graves' disease without anti-thyroid
      drug treatment took part in the study. Secondly, a control group, 15 examinees
      (three men, 12 women; mean age +/- SD, 45.3 +/- 13 years) each with a history of
      Graves' disease and post-medical treatment were recruited. This group showed
      normal thyroid function. Finally, a normal group, 32 physical check-up examinees
      with non-specific medical histories and normal thyroid functions, were recruited.
      Whole-body FDG PET was performed on all subjects. The intensity of FDG uptake in
      the thyroid, thymus and muscles region was graded subjectively on a five-point
      scale. RESULTS: Among the 20 patients with Graves' disease, only six (30%) showed
      thyroid uptake of FDG, 15 (75%) showed thymus uptake of FDG, and up to 19 (95%)
      showed symmetrical increased uptake of FDG in skeletal muscles. In particular,
      the skeletal muscle uptake of FDG in the psoas and rectus abdominis muscles was
      19/20 (95%) and 12/20 (60%), respectively. In the control group, three of the 15
      examinees showed thyroid uptake of FDG. In the normal group, four of the 32
      examinees had faintly visualized thyroid uptake of FDG. In thymus and skeletal
      muscles, there was no substantially increased FDG uptake in control and normal
      group examinees. CONCLUSIONS: In patients with Graves' disease, the thyroid
      uptake of FDG is not uniformly increased. Symmetrically increased uptake of FDG
      in the skeletal muscles and thymus is a clue for the diagnosis of Graves'
      disease. The uptake of FDG in skeletal muscles is more specific in the psoas and
      rectus abdominis muscles. An increment of muscle FDG uptake may be responsible
      for the high peripheral glucose utilization seen in Graves' disease.

PMID- 15154699
TI  - Subcortical [18F]fluorodeoxyglucose uptake in lesional epilepsy in patients with
      intracranial tumour.
AB  - BACKGROUND: We hypothesized that in patients with intracerebral tumours a
      subcortical metabolical shift may be present when the underlying pathology can,
      itself, be the epileptogenic focus. We also assumed that by studying the
      alterations in glucose metabolism beyond the tumour's borders we could identify a
      modulator area. METHODS: Sixty-seven patients with supratentorial brain tumour
      associated epilepsy were investigated interictally, in normoglycaemic conditions,
      by using [18F]fluorodeoxyglucose positron emission tomography (FDG PET). The
      studies were analysed semiquantitatively by calculating standardized uptake
      values and asymmetry indices. Normal subjects and patients with non-epileptic
      brain lesions were used as controls. RESULTS: Compared to normal controls frontal
      and temporal tumours showed significant changes in thalamic FDG uptake, which
      reflected hypometabolism of the affected side. It was noted in occipito-medial
      cortex in temporal tumours and in lentiform nucleus in frontal tumours as well.
      Comparison to lesional brains only proved that there was significant
      hypometabolism in lentiform nucleus in temporal tumours. CONCLUSIONS: The
      quantified values obviously reflect biological changes. The observed subcortical
      hypometabolism is most likely secondary to underlying pathology. Although
      seizures in tumorous patients do not originate from subcortical structures their
      influence on cortical sites of seizure initiation could be explained by defective
      subcortical regulation of cortical excitability.

PMID- 15154700
TI  - Clinical implications of the differences between diagnostic 123I and post-therapy
      131I scans.
AB  - BACKGROUND: 123I has been promoted for diagnostic imaging as a means of avoiding
      'stunning'. It has also been suggested that the more favourable physical
      characteristics and consequent enhanced imaging resolution provided by 123I
      offers a more accurate diagnostic assessment of the extent of disease prior to
      therapy. This study evaluated pairs of diagnostic 123I and post-therapy 131I
      scans for differences in patterns of radioiodine uptake. METHODS: Thirty-eight
      patients (31 women and seven men) with a history of differentiated thyroid cancer
      underwent 41 diagnostic 123I studies. 131I therapy was administered to 29
      patients as soon as possible after positive diagnostic findings were confirmed
      (with one patient being treated twice during the study period, making 30
      treatments). Post-treatment scans were obtained an average of 5.8 days after
      therapy. RESULTS: Qualitative comparison of diagnostic 123I and post-therapy 131I
      scans revealed a decrease in the extent of post-treatment uptake in four of the
      30 treatments (13%). Seven patients (23%) demonstrated increased uptake on their
      post-therapy 131I scan. CONCLUSIONS: Because the physical characteristics of 123I
      make it inconceivable that it could cause stunning, the decrease in post
      treatment uptake seen in 13% of patients from this series increases the
      likelihood that this pattern is due to factors other than stunning, such as
      differential rates of radioiodine turnover. In addition, the increase in extent
      of post-therapy uptake seen in 23% of patients suggests that diagnostic imaging
      with 123I is vulnerable to the same pre-therapy staging inaccuracies as is low
      dose diagnostic imaging with 131I. Further work is needed to determine whether
      larger diagnostic doses of 123I might mitigate this problem.

PMID- 15154701
TI  - Sentinel node scintigraphy in breast cancer using a dual tracer technique.
AB  - AIM: In order to depict the anatomy and improve the localization, sentinel node
      scintigraphy in breast cancer was combined with intravenous administration of
      pertechnetate. As this may reduce the detectability of weak 'hot spots', the
      number of lymph nodes detected at scintigraphy and at surgery in one group of
      patients was compared with that obtained in another group that had not received
      pertechnetate. PATIENTS AND METHODS: The number of 'hot spots' at frontal and
      lateral views in 47 female patients at scintigraphy performed 2-3 h after
      subcutaneous injection of radiocolloid together with 25 MBq pertechnetate i.v.
      was compared in retrospect with that of 41 female patients who had not received
      pertechnetate. The number of lymph nodes detected at surgery using a hand-held
      gamma probe together with blue dye in the two groups was also compared. The
      washout kinetics of pertechnetate was studied in 10 patients. RESULTS: There was
      no difference in the number of detected lymph nodes at any comparison. The
      kinetics study revealed a decreasing activity with time after correction for
      physical decay. CONCLUSION: Administration of a 25 MBq pertechnetate i.v. in
      order to improve the anatomical localization at sentinel node scintigraphy in
      breast cancer does not reduce the detectability of radioactive lymph nodes.

PMID- 15154702
TI  - Sentinel node biopsy in male breast cancer.
AB  - OBJECTIVE: Male breast cancer is a rare disease and axillary status is the most
      important prognostic indicator. Lymphoscintigraphy associated with gamma-probe
      guided surgery has been proved to reliably detect sentinel nodes in female
      patients with breast cancer. This study evaluates the feasibility of the surgical
      identification of sentinel node by using lymphoscintigraphy and a gamma-detecting
      probe in male patients, in order to select subjects who would be suitable for
      complete axillary lymphadenectomy. METHODS: Colloid human albumin labelled with
      99Tc was administered to 18 male patients with breast cancer and clinically
      negative axillary lymph nodes. Lymphoscintigraphy was performed the day before
      surgery. An intraoperative gamma-detecting probe was used to identify sentinel
      nodes during surgery. RESULTS: Lymphoscintigraphy and biopsy of the sentinel node
      were successful in all cases. A total of 20 sentinel nodes were removed.
      Pathological examinations showed 11 infiltrating ductal carcinomas, two
      intraductal carcinomas and five intracystic papillary carcinomas. Six patients
      (33%) had positive sentinel node (micrometastases were found in three patients).
      These patients underwent axillary dissection; in five of them (83%) the sentinel
      node was the only positive node. Twelve patients (67%) showed negative sentinel
      nodes; in all of them no further surgical treatments were planned. CONCLUSIONS:
      As in women, lymphoscintigraphy and sentinel node biopsy under the guidance of a
      gamma-detecting probe proved to be an easy method for the detection of sentinel
      nodes in male breast carcinoma. In male patients with early stage cancer,
      sentinel node biopsy might represent the standard surgical procedure in order to
      avoid unnecessary morbidity after surgery, preserving accurate staging of the
      disease in the axilla.

PMID- 15154703
TI  - The use of scintimammography for detecting the recurrence of loco-regional breast
      cancer: histopathologically proven results.
AB  - BACKGROUND: 99mTc tetrofosmin scintimammography has been shown to be an accurate
      diagnostic test in patients with a symptomatic breast lesion and for whom a non
      diagnostic mammogram has been obtained. Since a physical examination and
      conventional imaging modalities have their limitations in the detection of
      recurrent breast cancer, and survival is related to the extent of recurrent
      disease, complementary imaging modalities are warranted. AIM: To evaluate the
      role of 99mTc tetrofosmin scintimammography in detecting the recurrence of loco
      regional breast cancer. PATIENTS AND METHODS: Fifty-four patients underwent 55
      scintimammography studies because either there were clinical indications of
      breast metastases, or there was a recurrence of metastases in the chest wall,
      and/or an evaluation of axillary, parasternal, supraclavicular and/or
      infraclavicular lymph node metastases was required. Planar breast imaging was
      performed 10 min after intravenous injection of 700 MBq 99mTc tetrofosmin.
      RESULTS: 99mTc tetrofosmin scintimammography was diagnostic in 50 of the 55
      studies. An unknown lung metastasis was detected in one patient, and an unknown
      bone metastasis of the sternum was detected in another. Tumour involvement
      remained undetected in one neck node metastasis. Three patients had false
      positive scintimammography results, with 99mTc tetrofosmin uptake in an axillary,
      infraclavicular and parasternal lymph node, respectively. A fourth patient showed
      99mTc tetrofosmin uptake in the scar, which appeared to be an inflammatory
      lesion, proven by a histopathological biopsy and 1 year clinical follow-up.
      CONCLUSION: 99mTc tetrofosmin scintimammography accurately detected 100% of the
      local recurrences independently of the extent of the preceding surgical
      intervention. The sensitivity and specificity of the technique for the detection
      of regional recurrent disease were 93% and 90%, respectively. These results are
      substantially higher than those of other imaging modalities.

PMID- 15154704
TI  - The influence of renal function on normalized residual activity.
AB  - OBJECTIVE: To quantify the influence of overall renal function on normalized
      residual activity (NORA) and to evaluate the modifying factors. METHODS: A
      computer simulation model generated renograms by convolution of plasma
      disappearance curves with artificially created retention functions. From a
      database, 1099mTc-MAG3 plasma curves were selected, corresponding to renal
      clearances ranging from 33 to 405 ml x min(-1). The retention functions had three
      properties: (1) until the minimal transit time (MinTT), no output and a linear
      increase in transit time after MinTT; (2) a ratio of MinTT to mean transit time
      (MTT) equal to 0.3 or 0.8; and (3) a MTT between 3 and 60 min, increasing in
      steps of 1 min. The model generated 1160 renograms and for each of them the NORA
      was calculated at 20, 40 and 60 min. For each value of MTT, the coefficient of
      variation (CV) of the NORA was calculated at 20, 40 and 60 min. RESULTS: For the
      same retention function, different clearances resulted in different values of
      NORA. The degree of variability of NORA depended on several factors, including
      the time of measurement, the MTT and the MinTT to MTT ratio. For clearances
      between 100 and 400 ml x min(-1), the CV of the NORA ranged from 15% to 30%,
      whilst for clearances below 100 ml x min(-1), the CV of the NORA ranged from 22%
      to 67%. Little influence of the MinTT to MTT ratio was observed. CONCLUSION: NORA
      is influenced by overall renal function. The influence is limited for 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) renal clearances over 100 ml x min(-1),
      whilst for clearances less than 100 ml x min(-1), the NORA is influenced much
      more.

PMID- 15154705
TI  - Which single blood sample method should be used to estimate 51Cr-EDTA clearance
      in adolescents?
AB  - Single blood sample methods are widely used for the estimation of the glomerular
      filtration rate, but the methods recommended for adults are not the same as those
      for children. The question arises, therefore, as to which method should be used
      in an adolescent or young adult. The aim of this study was to compare the
      performance of two methods, a specific paediatric converting equation and an
      adult algorithm, in a group of adolescent and young adult patients. From a large
      database of 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) renal clearance
      determinations using the two blood sample method, 598 patients, aged 1 week to 90
      years, were selected. The results of the 51Cr-EDTA slope intercept clearance of
      the two blood sample method were used as reference. Using the paediatric
      algorithm, no bias was observed until the age of 40 years. Then, an increasing
      positive bias occurred. The standard deviation of the difference was generally
      less than 4 ml/min until the age of 25 years and increased gradually to reach 7
      ml/min at the age of 80 years. Using the Christensen and Groth adult algorithm,
      the best results were observed in patients older than 50 years. With the
      exception of children aged less than 5 years, no systematic bias was observed.
      The standard deviation, however, increased gradually and reached a value of
      around 8 ml/min in young children. For individuals aged 15-25 years, the mean of
      the difference between the paediatric algorithm and the slope intercept method
      was -1.1 ml/min, with a standard deviation of the difference of 3.3 ml/min. For
      the adult algorithm, the mean of the difference was 0.3 ml/min, with a standard
      deviation of the difference of 7.7 ml/min. It can be concluded that, for
      individuals aged 15-25 years, both methods performed correctly. In this series,
      the paediatric method gave better results than the adult algorithm, and its use
      is therefore recommended.

PMID- 15154706
TI  - Optimization of the uptake method for estimating renal clearance of 99mTc
      mercaptoacetyltriglycine.
AB  - OBJECTIVE: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance
      in the renal uptake method by optimizing the conditions of renal depth,
      background, threshold for renal boundary determination, and time interval for
      integrating renal counts. METHODS: Dynamic renal imaging was performed in 232
      patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5
      3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50%
      and 70% of the highest renal pixel counts were used. For drawing the backgrounds,
      circumferential and lateral-inferior quadrant peri-renal ROIs were used. For
      setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post
      injection were used. For determining renal depth, three methods of a theoretical
      exponential function using scatter fraction, Tonnesen's formula, and linear
      combination of scatter fraction and Tonnesen's formula were used. The scatter
      fraction was calculated using the counts in renal ROIs in the two energy windows.
      Using every combination of these conditions, renal uptake was calculated. As a
      reference, one-sample clearance was calculated from a blood sample taken at 30
      min post-injection following Bubeck's formula. According to the methods for
      estimating renal depth, three non-linear regression models were derived to
      convert renal uptake to clearance. Using one-sample clearance and integrated
      renal counts as dependent and independent variables, data were fitted to the
      models to determine the necessary constants. The correlations between the model
      estimated clearances and one-sample clearance were investigated. RESULTS: One
      sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half
      of the regression using renal depth determined by the scatter fraction alone
      failed to converge. Among the successfully converged regressions, all model
      estimated clearances showed significant correlations (P<0.01) with one-sample
      clearance. The best correlation was observed in the model using renal depth
      determined by the combination of scatter fraction and Tonnesen's formulas, renal
      ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min
      (r=0.898, P<0.001). CONCLUSION: The renal uptake method for estimating the
      clearance of mercaptoacetyltriglycine can be improved by the processing
      conditions proposed here.

PMID- 15154707
TI  - Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected
      for renal size.
AB  - BACKGROUND: Decreased relative 99mTc dimercaptosuccinic acid (99mTc-DMSA) uptake
      can be a consequence of abnormal kidney size, associated with normal or impaired
      function. When there is a small kidney, relative 99mTc-DMSA uptake is decreased,
      and it is sometimes difficult to distinguish a small, normal kidney from a
      hypofunctioning kidney. Here, relative renal function was studied by quantifying
      the relative 99mTc-DMSA uptake corrected for renal size (RCU). METHODS: Five
      hundred and fifty-five consecutive patients (184 adults) aged 1 month to 82 years
      (mean, 14.8 years) underwent a 99mTc-DMSA study for various renal diseases.
      Results were compared with the relative 99mTc-DMSA uptake without size correction
      (RUU). Visual evaluation of images was also performed. RESULTS: In 288 patients
      (52%) the relative 99mTc-DMSA uptake was normal, either uncorrected or corrected,
      for renal size; in 184 (33%) it was abnormal by both quantification methods; and
      in 83 (15%) it was abnormal only by one method. Two hundred and fifty-seven
      patients (46%) presented with decreased RUU in one kidney, associated with a
      small kidney in 73 patients (13%). RCU was normal in all of these 73 patients
      (100%, P<0.0001). The sensitivity and specificity of RCU for evaluating renal
      function in relation to small renal size and with respect to RUU were 72% and
      97%, with positive and negative predictive values of 95% and 80%, and an accuracy
      of 85%. Visual analysis of the 73 studies with decreased RUU and normal RCU
      showed a small, normal kidney on 55 occasions (75%), cortical scars in eight
      (11%), and impaired bilateral function in 10 (14%). Visual analysis of 10 studies
      with normal RUU and decreased RCU showed dilated pyelocalyceal system in seven
      occasions (70%) and normal kidneys in three (P<0.0001). CONCLUSION: It is
      concluded that relative 99mTc-DMSA uptake corrected for renal size is a more
      accurate method for assessing individual renal function. When there is a small
      kidney, relative 99mTc-DMSA uptake corrected for renal size can distinguish
      between a normal and a hypofunctioning kidney.

PMID- 15154708
TI  - The usefulness of 99mTc sulfur colloid bone marrow scintigraphy combined with
      111In leucocyte scintigraphy in prosthetic joint infection.
AB  - AIM: To assess the extent to which bone marrow scintigraphy (BMS) makes the
      interpretation of leucocyte scintigraphy (LS) easier and improves its diagnostic
      value. METHODS: Seventy-three 111In LSs, 99mTc hydroxymethylene diphosphonate
      bone scintigraphies (BSs) and 99mTc sulfur colloid BMSs were performed in 60
      patients with suspected infection related to a hip prosthesis or knee prosthesis,
      either in situ (+group, n = 43) or after removal for septic loosening (-group, n
      = 30). Bacteriological samples were obtained from all patients. LS was
      interpreted together with BS (LS-BS) or with BMS (LS-BMS) by three independent
      readers. RESULTS: The concordance among readers, estimated by the kappa test, was
      average with LS-BS (kappa/kappam coefficients = 0.58, 0.58 and 0.46,
      respectively, for the three pairs of readers) and excellent with LS-BMS
      (kappa/kappam coefficients = 1.00 for the three pairs of readers). With LS-BS,
      64/219 interpretations were equivocal whereas only one was equivocal with LS-BMS.
      Sensitivity, specificity and accuracy of LS-BMS were, respectively, 80%, 94% and
      91% in the +group, and 33%, 100% and 93% in the -group. CONCLUSION: We conclude
      that (1) the interpretation of the results for LS-BMS is very easy, in contrast
      to LS-BS; (2) the diagnostic value of LS-BMS for detecting infected joint
      prostheses is good; and (3) additional data are needed to assess the accuracy of
      LS-BMS when the prosthesis has been removed.

PMID- 15154709
TI  - Application of a neuropsychological activation probe with SPECT: the 'Tower of
      London' task in healthy volunteers.
AB  - BACKGROUND: Human planning is a complex mental process that may be evaluated by
      the 'Tower of London' (TOL) task, which includes setting up and maintaining
      multiple subgoals at the same time. Although positron emission tomography and
      functional magnetic resonance imaging have provided reliable data on the
      recruitment of a neural network engaged in planning tasks, the experimental
      settings of these studies cannot be applied in clinical conditions. Hence, this
      study reports on the TOL task under classical neuropsychological test conditions
      using single photon emission computed tomography (SPECT) activation in 10 healthy
      subjects. METHODS: Participants first performed a control task and then an
      activation task, i.e., the TOL planning task In the planning task, subjects were
      required to change, in the minimum number of moves possible, an initial
      arrangement of beads to match a goal arrangement. Subjects solved a set of eight
      TOL problems of increasing difficulty. A control task was designed such that it
      eliminates planning abilities, which is the process of interest. Planning times
      and accuracy were measured as performance parameters and functional imaging data
      were analysed with statistical parametric mapping (SPM99) to determine
      significant voxel-wise activations between the planning task and the control
      task. RESULTS: Both overall and for each difficulty level, measures of accuracy
      were within the normal range. Similar results were found for the overall thinking
      time and thinking times of each difficulty level. That is, performance of the
      healthy subjects during the TOL task replicated the typical pattern of results
      found with appropriate control samples in the literature. Also, activation of the
      right prefrontal cortex was consistent with other functional imaging results,
      thereby validating the use of the TOL task in a SPECT activation paradigm.
      CONCLUSIONS: Based on the present study it may be concluded that the close
      resemblance of the test conditions of the SPECT activation procedure with those
      of the TOL task in the investigation room constitutes a major advantage for
      future application of the SPECT activation procedure in clinical conditions.

PMID- 15154710
TI  - Pulmonary perfusion assessment with respiratory gated 99mTc macroaggregated
      albumin SPECT: preliminary results.
AB  - PURPOSE: Respiratory gated perfusion single photon emission computed tomography
      (SPECT) was applied to reduce respiratory lung motion effects and to reliably
      assess perfusion impairment in various lung diseases. METHODS: After injection of
      259 MBq of 99mTc macroaggretated albumin (99mTc-MAA), gating was performed using
      a triple-headed SPECT unit connected to a physiological synchronizer in a total
      of 35 patients with either obstructive lung diseases (n = 14), pulmonary embolism
      (n = 8), small lung nodules (n = 7) or acute interstitial pneumonia (n = 6).
      Projection data were acquired in a 64 x 64 matrix, with 20 stops over 120 degrees
      for each detector with a preset time of 15 s for each stop. Inadequate data for
      the respiratory cycle were automatically eliminated. In addition to end
      inspiration images and end expiration images derived from 12.5% threshold data
      centred at peak inspiration and expiration for each respiratory cycle,
      respectively, an ungated image was obtained from full respiratory cycle data.
      RESULTS: Gated images were completed for 13.7 +/- 1.8 min in all subjects.
      Although the total lung radioactivity of the gated images were reduced to
      approximately 13% of that of the ungated images, these gated images showed
      uniform perfusion in the unaffected lungs and visualized a total of 94 (21.9%)
      additional perfusion defects against 429 defects visualized on ungated images in
      31 patients with focal perfusion defects. Among the perfusion defects visualized
      on both gated images, the defect size was occasionally larger on the end
      inspiration images. The end expiration images showed significantly higher lesion
      to-normal lung radioactivity ratios compared with those on the end expiration and
      ungated images in the affected lower lungs throughout the lung diseases.
      Radioactivity changes per pixel between end inspiration and end expiration images
      in the affected lower lungs of the obstructive lung diseases were significantly
      lower compared with those of pulmonary embolism and acute interstitial pneumonia
      (P<0.0001 and P<0.01, respectively). CONCLUSION: This technique appears to
      enhance the clarity of perfusion defects, and lung radioactivity changes between
      end inspiration and end expiration may characterize regionally impaired
      ventilation status.

PMID- 15154711
TI  - Irbesartan has a masking effect on dipyridamole stress induced myocardial
      perfusion defects.
AB  - BACKGROUND AND AIM: The angiotensin II type 1 (AT1) receptor antagonist
      irbesartan is used for the treatment of hypertension, but its anti-ischaemic
      effect is not yet known. Our aim was to assess the effect of irbesartan
      administration on the diagnostic yield of 99mTc sestamibi single photon emission
      computed tomography (SPECT) in patients with coronary artery disease (CAD) after
      dipyridamole stress. METHODS: Our study group consisted of 13 patients (11 men
      and two women; mean age, 53.3 +/- 10.6 years; body mass index, 26.9 +/- 3.3 kg x
      m(-2)) with angiographically documented CAD. All patients underwent SmTc
      sestamibi SPECT studies at rest, before (STRESS-1) and 2 weeks after irbesartan
      (150 mg daily) administration (STRESS-2) at dipyridamole stress. The extent and
      severity of defects were analysed by using visual and quantitative 99mTc
      sestamibi SPECT. RESULTS: The mean summed stress score was significantly higher
      during the STRESS-1 study than the STRESS-2 study (13.2 +/- 7.4 vs. 11 +/- 7.4,
      P=0.003). The mean size of perfusion defects at stress was significantly larger
      for the STRESS-1 group than the STRESS-2 group (17.8% +/- 2.85% vs. 15.3% +/-
      2.95%, P=0.01). CONCLUSION: Our study showed that the AT1 receptor blocker
      irbesartan reduces the extent and severity of 99mTc sestamibi perfusion defects
      after dipyridamole stress in patients with CAD. Irbesartan may alter coronary
      blood flow reserve. The continued use of irbesartan before stress myocardial
      perfusion SPECT has a masking effect on stress induced myocardial perfusion
      defects. For this reason AT1 receptor blockers must be stopped before stress
      myocardial perfusion scintigraphic examinations.

PMID- 15154712
TI  - Regional wall motion and wall thickening visual scores from gated SPECT in
      anterior and infero-lateral myocardial infarctions.
AB  - BACKGROUND: The relationship between the visual scores for wall motion (WM) and
      wall thickening (WT) of different left ventricular regions in patients with
      anterior and infero-lateral myocardial infarctions was evaluated using gated
      SPECT. METHODS: Ninety consecutive patients (79 men and 11 women; mean age 56 +/-
      9 years) with previous myocardial infarction (33 anterior and 57 infero-lateral)
      were included. Left ventricular volumes and ejection fractions (EFs) were
      calculated from quantitative rest gated SPECT 99mTc tetrofosmin images by using
      the QGS automatic algorithm. Global and regional (anterior, septal, inferior and
      lateral) wall motion and wall thickening scores were calculated by consensus of
      three experienced observers. RESULTS: The correlation between EFs and wall motion
      and wall thickening scores was better for WM scores in anterior (r=0.904,
      P<0.0001) than infero-lateral infarctions (r=0.674, P<0.0001). Correlation
      between wall motion and wall thickening scores was also better for anterior
      (r=0.898, P<0.0001) than for infero-lateral infarctions (r=0.750, P<0.0001).
      Except in septal regions, WT scores of the different regions were higher than WM
      scores (P<0.05) but the statistical significance was higher (P<0.001) in inferior
      and lateral regions of infero-lateral infarctions. CONCLUSION: Visual global wall
      motion and wall thickening scores obtained by gated SPECT showed good correlation
      between them and with the EF, but differences were observed between regional wall
      motion and wall thickening, especially in inferior and lateral regions of
      patients with infero-lateral infarctions.

PMID- 15154713
TI  - Assessment of digital ischaemia and evaluation of response to therapy by 99mTc
      sestamibi limb scintigraphy after local cooling of the hands in patients with
      vasospastic Raynaud's syndrome.
AB  - AIM: Cold induced arteriolar constriction in patients with vasospastic Raynaud's
      syndrome (VRS) produces temporary digital ischaemia. The aim of this study was to
      ascertain whether 99mTc sestamibi scintigraphy is useful in the diagnosis and the
      monitoring of treatment in VRS. METHODS: Fifteen patients with VRS and 20 matched
      normal controls underwent examination. Twelve patients with VRS received therapy.
      For each patient, one hand was immersed in iced water for 30s while the other
      hand served as a control. Ten minutes after cooling, 99mTc sestamibi was injected
      and imaging was performed 60min later. The per cent decrease of the perfusion
      (%DP) was calculated by semiquantitative analysis to determine the severity of
      hypoperfusion. RESULTS: In all patients with VRS, moderate or marked
      hypoperfusion were seen in 99mTc sestamibi images after exposure to the iced
      water, while there was minimal or mild hypoperfusion in the control groups.
      Values for %DP were 46.86 +/- 19.04 and 7.85 +/- 4.53 for the VRS group and
      normal subjects, respectively. The difference between both groups was
      statistically significant (P = 0.0000). In 12 treated patients with VRS, pre
      treatment and post-treatment %DP values were 51.16 +/- 18.42 and 33.58 +/- 17.83,
      respectively, and a significant difference was seen between both values (P =
      0.001). However, there was still a statistically significant difference between
      control subjects and post-therapy values (7.85 +/- 4.53 vs. 33.58 +/- 17.83, P =
      0.0000). The +/- 95% confidence interval of DP for control subjects was 5.7-10%
      (chi-squared, P = 0.000). When a DP of 10% was used as a cut-off point,
      sensitivity, specificity and diagnostic accuracy were 100%, 70% and 83%,
      respectively, for the 99mTc sestamibi scan. There was also a strong correlation
      between %DP and the duration of the disease (r = 0.80, P = 0.0003). CONCLUSION:
      The results of this study indicate that a 99mTc sestamibi scan is a valuable
      imaging method for the determination of digital ischaemia in vasospastic
      Raynaud's syndrome, and may play a role in evaluating the response to therapy.

PMID- 15154714
TI  - President Walther encourages federal funding to battle CWD.

PMID- 15154715
TI  - Animal welfare: status and perception.

PMID- 15154716
TI  - The animal rights struggle.

PMID- 15154717
TI  - Evaluating humane slaughter.

PMID- 15154718
TI  - Legislation presses limits of animal status in New York.

PMID- 15154719
TI  - Seeks animal friendly curriculums.

PMID- 15154720
TI  - More on cat and dog vaccinations.

PMID- 15154721
TI  - Dr. Dodds provides references.

PMID- 15154722
TI  - Surprised with feline hyperthyroidism study recommendation.

PMID- 15154723
TI  - Raises questions concerning liposarcomas in dogs.

PMID- 15154724
TI  - What is your diagnosis? Pulmonary lymphoma.

PMID- 15154725
TI  - ECG of the month. Pulmonic stenosis.

PMID- 15154726
TI  - Theriogenology question of the month. Lymphosarcoma infiltrating the uterus,
      cervix, and vagina.

PMID- 15154727
TI  - Animal behavior case of the month. Urine spraying and inappropriate urination for
      the past 10 years.

PMID- 15154728
TI  - Economic considerations for diagnostic and control options for Neospora caninum
      induced abortions in endemically infected herds of beef cattle.
AB  - OBJECTIVE: To compare economic outcome for herds not exposed to Neospora caninum
      with that for herds with various seroprevalences of N caninum infection and
      evaluate 3 control strategies. DESIGN: Economic simulation model. SAMPLE
      POPULATION: Beef herds with various seroprevalences of N caninum infection.
      PROCEDURE: A 5-year simulation model was used. Control strategies that were
      evaluated included culling females that fail to calve, selling seropositive
      females and purchasing seronegative replacements, and excluding the daughters of
      seropositive dams as potential replacements. RESULTS: For a 5-year period with
      low prices for feeder calves, endemic N caninum infection decreased mean return
      to fixed assets by 22.2% when true seroprevalence was 10% and by 29.9% when true
      seroprevalence was 70%. Percentage decrease in return to fixed assets was less
      dramatic when a 5-year period with high prices for feeder calves was evaluated.
      Analysis indicated that 2 control strategies (culling females that fail to give
      birth to a calf and selling seropositive female cattle and purchasing
      seronegative replacement female cattle) were not likely to be economically
      beneficial. The third control strategy (testing the entire herd for N caninum
      infection and excluding the female offspring of seropositive dams as
      replacements) appeared to be a reasonable control strategy. CONCLUSIONS AND
      CLINICAL RELEVANCE: For the assumptions in the model, endemic N caninum infection
      decreases return to fixed assets for cow-calf herds. Of the potential control
      strategies evaluated, testing the entire herd for N caninum infection and
      excluding the daughters of seropositive dams as potential replacements provided
      the best economic return.)

PMID- 15154729
TI  - Congenital ectopic ureters in a continent male dog and cat.
AB  - A male dog and cat were evaluated because of clinical signs associated with
      hydronephrosis. Both animals had ectopic ureters, but neither had urinary
      incontinence. The diagnoses were made by use of ultrasonography, excretory
      urography, retrograde urethrocystography, and surgery. In both animals,
      hydronephrosis was bilateral but of unequal severity, such that unilateral
      ureteronephrectomy could be performed. Both animals underwent
      ureteroneocystostomy of the remaining ureter. This treatment resulted in good
      clinical outcome during follow-up periods of 18 months and 3 years.

PMID- 15154730
TI  - Transient proximal renal tubular acidosis and Fanconi syndrome in a dog.
AB  - A 9-year-old spayed female Labrador Retriever was evaluated for anorexia,
      lethargy, and vomiting of 5 days' duration. Laboratory abnormalities included
      azotemia, high liver enzyme activities, hyperchloremic metabolic acidosis,
      glucosuria, ketonuria, proteinuria, and aminoaciduria. These laboratory
      abnormalities were diagnostic of proximal renal tubular acidosis and Fanconi
      syndrome. Results of initial and convalescent serologic tests for leptospirosis
      were negative. The dog was treated with amoxicillin, sodium bicarbonate, and
      potassium citrate at discharge. Repeated evaluations revealed resolution of the
      acidosis, azotemia, proteinuria, glucosuria, ketonuria, and high liver enzyme
      activities. Alkali administration was gradually discontinued, and the dog was
      clinically normal 8 months after discharge. The dog's clinical condition appeared
      to have been transient in nature, a phenomenon that is rarely seen in human or
      veterinary medicine.

PMID- 15154731
TI  - Gallbladder mucocele in dogs: 30 cases (2000-2002).
AB  - OBJECTIVE: To determine long-term outcome of dogs with gallbladder mucocele.
      DESIGN: Retrospective study. ANIMALS: 30 dogs with gallbladder mucocele,
      including 23 that underwent cholecystectomy. PROCEDURE: Medical records were
      reviewed for signalment, history, and clinical, ultrasonographic, and surgical
      findings. Follow-up information was obtained for all dogs that survived the
      perioperative hospitalization period. RESULTS: 23 dogs had signs of systemic
      illness; 7 had no clinical signs. Median values for serum activities of alanine
      aminotransferase and alkaline phosphatase, serum total bilirubin concentration,
      and total WBC count were significantly higher among dogs with gallbladder rupture
      than among dogs without rupture. Sensitivity of sonography for detection of
      rupture was 85.7%. Overall perioperative mortality rate for dogs that underwent
      cholecystectomy was 21.7%; mortality rate was not significantly greater for dogs
      with rupture. Aerobic bacteria were isolated from the bile or gallbladder wall in
      8.7% of dogs. All 18 dogs discharged from the hospital had complete resolution of
      clinical signs. In dogs that underwent in-hospital reexamination, serum liver
      enzyme activities were significantly decreased, compared with preoperative
      activities. Persistent increases in serum activities of 1 or more liver enzymes
      were detected in 9 of 12 dogs; 6 of 12 dogs had persistent abnormalities in
      hepatic echogenicity. Mean follow-up period was 13.9 months. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that cholecystectomy is an effective
      treatment for gallbladder mucocele. Although perioperative mortality rate is
      high, prognosis after discharge from the hospital is excellent. Rupture of the
      gallbladder warrants emergency surgical intervention but does not preclude a
      positive outcome.

PMID- 15154733
TI  - Gracilis muscle injury as a cause of lameness in two horses.
AB  - Injury to the gracilis muscle can cause acute, severe lameness in horses. Two
      female Quarter Horses that were used for barrel racing sustained gracilis muscle
      tear injuries. The site of injury was localized by direct infiltration of the
      area with mepivacaine. The extent of muscle tearing and seroma formation was
      determined via ultrasonographic evaluation. One horse developed fibrotic myopathy
      approximately 3 months after the original injury and underwent surgery to
      transect a palpable fibrous band at the previous injury site. Both horses
      returned to barrel racing 5 to 6 months after the injury These results suggest
      that horses sustaining a gracilis muscle injury have a good prognosis for
      returning to athletic use after an adequate period of muscle healing; however,
      fibrotic myopathy or muscle atrophy could be a complication of the injury
      resulting in persistent gait deficits.

PMID- 15154732
TI  - Evaluation of an epidemic of sporotrichosis in cats: 347 cases (1998-2001).
AB  - OBJECTIVE: To evaluate characteristics of a large epidemic of sporotrichosis in
      cats. DESIGN: Retrospective study. ANIMALS: 347 cats with naturally acquired
      infection with Sporothrix schenckii. PROCEDURE: Medical records were reviewed for
      data regarding clinical, mycologic, histopathologic, and routine hematologic and
      serum biochemical findings; assays for FIV-specific antibodies and FeLV antigen;
      antifungal treatment; and follow-up. RESULTS: Lesions varied from small papules
      to extensive zones of necrosis. Ten cats had no skin lesions, 114 had skin
      lesions at a single site, 86 had skin lesions in 2 sites, and 137 had skin
      lesions in 3 or more sites. Respiratory tract signs were observed in 154 cats and
      were the most frequent extracutaneous sign. Anemia, leukocytosis with
      neutrophilia, hypoalbuminemia, and hyperglobulinemia were the main blood
      abnormalities. Antibodies against FIV were detected in 28 cats, FeLV antigen was
      detected in 2 cats, and both were detected in 1 cat among 142 cats tested. During
      the study, 118 cats were lost to follow-up and 124 died. Of 266 cats that were
      treated, 68 were cured. Complete healing of the lesions was observed regardless
      of the presence of extracutaneous signs, general condition, treatment schedule,
      or coinfection with FIV. CONCLUSIONS AND CLINICAL RELEVANCE: Feline
      sporotrichosis was evident in subclinical to severe forms; however, cats can
      respond well to regular and prolonged antifungal treatment.

PMID- 15154734
TI  - Efficacy of ceftiofur hydrochloride sterile suspension administered parenterally
      for the treatment of acute postpartum metritis in dairy cows.
AB  - OBJECTIVE: To evaluate the efficacy of ceftiofur hydrochloride sterile suspension
      administered parenterally for treatment of acute postpartum metritis (APM) in
      dairy cows. DESIGN: Multilocation, randomized block, field trial. ANIMALS: 406
      cows in the first 14 days postpartum. PROCEDURE: Cows with rectal temperatures >
      or = 39.5 degrees C (103.1 degrees F) without clinical signs of respiratory or
      gastrointestinal tract disease and with a fetid vaginal discharge were allocated
      randomly in blocks of 3 to 3 treatment groups: sterile saline (0.9% NaCl)
      solution administered at a dosage of 2 mL/45.4 kg (2 mL/100 lb), SC or IM, once
      daily for 5 days (control); or ceftiofur hydrochloride administered at a dosage
      of 1.1 or 2.2 mg of ceftiofur equivalents (CE)/kg (0.5 or 1 mg/lb, respectively),
      SC or IM, once daily for 5 days. Cows were evaluated on days 6, 10, and 14, and
      clinical cure or failure to cure was determined. Clinical cure was defined as no
      additional antimicrobial treatment administered, rectal temperature < 39.5
      degrees C, and absence of a fetid vaginal discharge. RESULTS: On day 14, clinical
      cure rates were 77%, 65%, and 62% for the 2.2 mg of CE/kg, 1.1 mg of CE/kg, and
      control groups, respectively. No significant differences were detected in
      clinical cure rates between control and treatment groups on day 10 or 6.
      CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur hydrochloride administered at a
      dosage of 2.2 mg of CE/kg, SC or IM, once daily for 5 days was efficacious for
      treatment of APM in dairy cows.

PMID- 15154735
TI  - Clinical signs and results of specific diagnostic testing among captive birds
      housed at zoological institutions and infected with West Nile virus.
AB  - During 2002, West Nile virus (WNV) infection was diagnosed in 11 birds housed in
      outdoor exhibits at 5 zoological institutions in Kansas. Eight birds were
      examined because of neurologic abnormalities; 2 died suddenly without any
      clinical signs of disease. Results of CBCs and serum biochemical testing were
      nonspecific. Results of a plaque reduction neutralization test to detect
      circulating antibodies against WNV were positive for 2 of 8 birds. Results of a
      reverse transcriptase-polymerase chain reaction assay of an oral cavity swab
      specimen for WNV RNA were positive for 4 of 5 birds. One bird survived; the
      remaining 10 died or were euthanatized, with 9 of the 10 dying or being
      euthanatized within 3 days of the onset of clinical signs. In all 10 birds that
      died or were euthanatized, WNV infection was confirmed on postmortem examination
      by means of specific testing. Findings in these birds suggest that West Nile
      virus infection can be difficult to diagnose antemortem because clinical signs
      mimic those associated with other more common avian diseases. Neither of the
      antemortem diagnostic tests was definitive for diagnosing WNV infection in these
      cases.

PMID- 15154736
TI  - Cryptobia iubilans infection in juvenile discus.
AB  - Four commercial producers of discus (Symphysodon aequifasciatus) were found to
      have fish infested with the flagellate Cryptobia iubilans. Affected fish had
      granulomatous gastritis, and many also had granulomatous disease of other organs.
      The parasite had to be differentiated from the related flagellates Spironucleus
      spp, which induce different lesions. Transmission electron microscopy was found
      to be useful in detecting and identifying the parasite. Morbidity and mortality
      rates in the various fish populations appeared to be linked to a number of
      variables, including water quality, presence of other parasites and bacteria,
      diet, species, size, and age of the fish, and optimization of husbandry appeared
      to be important in alleviating the severity of disease. Metronidazole was not
      effective for treatment of C iubilans, but bath treatments with dimetridazole (80
      mg/L for 24 hours, repeated daily for 3 days) or 2-amino-5-nitrothiazol (10 mg/L
      for 24 hours, repeated daily for 3 days) may be useful in decreasing the
      prevalence of infestation.

PMID- 15154737
TI  - Editorial perspective--advances in B-cell non-Hodgkin's lymphoma.
AB  - Radioimmunotherapy (RIT) represents an exciting new therapeutic option for the
      treatment of B-cell non-Hodgkin's lymphoma (NHL), emerging at a time when
      significant advances have been made in NHL classification, molecular genetics and
      treatment. Despite recent treatment advances, including the use of fludarabine
      phosphate-based combination chemotherapies, able to eradicate minimal residual
      disease, there remains much room for improvement. The incorporation of RIT into
      treatment schedules is an attractive option to exploit the extreme sensitivity of
      lymphoma cells to irradiation. In this supplement, we examine the potential
      future roles for RIT in the light of past and present therapies, existing RIT
      clinical data and the unique attributes of radiolabeled monoclonal antibodies.

PMID- 15154738
TI  - Traditional treatment approaches in B-cell non-Hodgkin's lymphoma.
AB  - Current treatment of non-Hodgkin's lymphoma (NHL) is based, to a large extent, on
      stratification of patients into groups based on disease subtype (indolent or
      aggressive) and stage, and still relies heavily on traditional approaches based
      on external beam irradiation and alkylating agent-based chemotherapy. Here, we
      describe risk-based patient management, and the benefits made possible by
      different treatments. Early-stage localized disease is effectively managed with
      irradiation and/or chemotherapy; chlorambucil in the case of indolent disease and
      CHOP-based therapy in the case of aggressive disease. Progress is underway in two
      crucial areas of the treatment of advanced-stage low-grade NHL: development of
      first-line therapies to improve the number and quality of complete responses
      (CRs), and investigation of novel radioimmunotherapy or monoclonal
      antibody/chemotherapy combination regimens to combat relapsed and refractory
      disease. New chemotherapy approaches, such as fludarabine phosphate-based
      combination chemotherapy for low-grade advanced-stage NHL have improved the
      number and quality of remissions in chemotherapy-naive and relapsed patients, but
      it remains to be seen what the long-term impact on survival may be. Monoclonal
      antibody based therapies including radioimmunotherapy, is emerging as a highly
      effective tool for the treatment of NHL, and shows synergy with fludarabine
      phosphate-based chemotherapy, though its optimal role has yet to be determined.
      At present, for patients with untreated disseminated disease; recurrent disease;
      or high-grade disease in the presence of poor risk factors; alternative treatment
      strategies are needed.

PMID- 15154740
TI  - The role of nuclear medicine in the treatment of non-Hodgkin's lymphoma (NHL).
AB  - The emergence of radioimmunotherapy (RIT) provides a new therapeutic approach in
      which monoclonal antibodies directed against tumor-specific antigens are used to
      target therapeutic radioisotopes to sites of disseminated disease. The target
      cell is eliminated and adjacent tumor cells, to which antibody has not bound, are
      also killed. To date, 90Y-ibritumomab tiuxetan and 131I-tositumomab are the only
      FDA-approved, and most extensively studied, radioimmunoconjugates for RIT of non
      Hodgkin's lymphoma (NHL). Both 90Y-ibritumomab tiuxetan and 131I-tositumomab
      utilize an anti-CD20 monoclonal antibody to target radioactivity to malignant B
      cells. 90Y-ibritumomab tiuxetan emits pure therapeutic beta radiation, permitting
      outpatient treatment. The high energy of the beta particles emitted by 90Y (2.3
      MeV) achieves a wide-ranging crossfire effect. Approximately 90% of the energy is
      deposited within 5 mm of the radiation source, which kills not only antibody
      bound cells but also neighboring malignant cells within a diameter of up to 12
      mm. In addition, the half-life of 90Y matches the in vivo biological half-life of
      the monoclonal antibody (64 h), with negligible excretion of 90Y in urine. With
      90Y-ibritumomab tiuxetan, hematological adverse events correlate with the degree
      of bone marrow involvement and the bone marrow reserve, rather than with
      dosimetric parameters, and doses to normal organs and red marrow are well below
      the accepted limits of 20 Gy to normal organs and 3 Gy to red marrow. A dosing
      schedule based on patient weight and baseline platelet counts has therefore been
      developed, and dosimetry is not routinely required. 131I, the isotope used in
      tositumomab RIT, emits both therapeutic beta radiation and highly penetrating
      gamma emissions. The lower energy of the beta particles emitted by 131I (0.6 MeV)
      achieves a crossfire effect of up to 2 mm in diameter, which is used to treat
      tumors. The gamma radiation emitted by 131I allows both dosimetry and
      biodistribution studies to be performed; such studies are important because the
      rate of 131I-tositumomab clearance varies among individuals. Therefore, dosimetry
      must be performed in each patient before the therapeutic dose of 131I-tositumomab
      is administered. Similarly, because of this variability in 131I clearance, the
      dosage of 131I-tositumomab is calculated accordingly for each patient. 131I
      tositumomab is a substrate for dehalogenases, which decouple the radioisotope
      from the antibody moiety, resulting in free, circulating 131I, which can
      accumulate in the thyroid. Patients who receive 131I-tositumomab therapy are
      usually hospitalized in radioprotection wards, and are treated by specially
      trained hospital staff. The administration of RIT requires an integrated team
      approach, involving nuclear medicine (or, in some countries, radiation oncology),
      hematology-oncology, nursing, radiopharmacy and radiation safety personnel.
      Effective collaboration between all members of the RIT team is essential to
      treatment success, and understanding the properties of these novel agents will
      facilitate their safe and effective administration.

PMID- 15154739
TI  - Current treatment options in aggressive lymphoma.
AB  - The overall percentage of patients achieving long-term remissions in aggressive
      non-Hodgkin's lymphoma (NHL) using CHOP or CHOP-based primary chemotherapy is
      only 40%. Much effort has therefore been concentrated on developing strategies to
      improve this figure. More intensive variants of CHOP chemotherapy, such as multi
      agent "third-generation" regimens, have failed to improve long-term survival, and
      are also associated with increased toxicity. Hence, there is a need for improved
      treatment regimens, both as primary therapy and for patients in first and
      subsequent relapse. This need is most acute in elderly patients (> 60 years of
      age), who comprise more than 50% of NHL cases and who may not be able to tolerate
      subsequent intensive chemotherapy at relapse. Approaches currently being examined
      to improve outcome include: the use of clinical, histological and molecular
      prognostic factors to establish a patient's risk group, and so define those
      patients most likely to benefit from early aggressive therapy; the inclusion of
      high-dose therapy and autologous transplantation; and the integration of novel
      therapies, such as immunotherapy and radioimmunotherapy, into existing treatment
      strategies. The impact of these approaches on the treatment of diffuse, large B
      cell lymphoma and mantle cell lymphoma is discussed below.

PMID- 15154741
TI  - Radioimmunotherapy for NHL: experience of 90Y-ibritumomab tiuxetan in clinical
      practice.
AB  - Radioimmunotherapy (RIT) is a novel treatment modality that combines the benefits
      of radiotherapy and immunotherapy, enabling multiple sites of disseminated
      disease to be treated simultaneously and effectively, while minimizing toxicity
      to normal tissues. 90Y-ibritumomab tiuxetan consists of the anti-CD20 monoclonal
      antibody (MAb) ibritumomab covalently linked to tiuxetan for chelation of 90Y for
      therapy. Early work established that a dose of 14.8 MBq/kg (0.4 mCi/kg) is safe
      and effective in patients with < 25% bone marrow involvement and adequate marrow
      reserves, as is a dose of 11.1 MBq/kg (0.3 mCi/kg) in patients with mild
      thrombocytopenia (platelet counts 100 x 10(9)-150 x 10(9)/l). To date, 5 clinical
      trials using 90Y-ibritumomab tiuxetan have been reported, one of which assessed
      the efficacy in rituximab-refractory patients with follicular non-Hodgkin's
      lymphoma (NHL) histology. Within the 54 follicular lymphoma patients, an overall
      response (OR) rate of 74% and a complete response (CR) rate of 15% were achieved,
      despite patients having received a median of 4 prior therapies and 73% having
      tumors > or = 5 cm in diameter. In addition, a major phase III randomized trial
      directly compared 90Y-ibritumomab tiuxetan with the unlabeled anti-CD20 MAb
      rituximab. Results from the randomized trial demonstrated that OR and CR rates
      were significantly higher with 90Y-ibritumomab tiuxetan, compared with rituximab
      (OR rate 80% vs. 56%, P = 0.002; CR rate 30% vs. 16%, P = 0.004). Time to
      progression (TTP) was 11.2 vs. 10.1 months (P = 0.173). Treatment was generally
      well tolerated; the primary toxicity associated with 90Y-ibritumomab tiuxetan
      therapy is reversible myelosuppression, which correlates with the degree of bone
      marrow involvement at baseline. In an integrated analysis of safety data from 5
      90Y-ibritumomab tiuxetan studies, only 7% of patients were hospitalized due to
      infection during the treatment period. In addition, 90Y-ibritumomab tiuxetan
      therapy was not shown to increase the risk of developing secondary malignancies
      (myelodysplastic syndrome/acute myeloid leukemia), or preclude subsequent therapy
      upon relapse. Current investigations are focussing on the potential role of 90Y
      ibritumomab tiuxetan earlier in the treatment algorithm, including as single
      agent therapy for relapsed diffuse large B-cell lymphoma patients not eligible
      for transplantation, and consolidation treatment for low-grade NHL patients after
      first-line, alkylating agent-based therapy.

PMID- 15154742
TI  - Nursing a patient during and after 90Y-ibritumomab tiuxetan (Zevalin) therapy.
AB  - Radioimmunotherapy (RIT) is a new cancer therapy that uses monoclonal antibodies
      to deliver targeted radiation to cancer cells, allowing multiple sites of
      disseminated disease to be treated simultaneously, while limiting toxicity to
      normal healthy tissue. 90Y-ibritumomab tiuxetan was the first RIT to be approved
      for the treatment of relapsed and refractory B-cell non-Hodgkin's lymphoma (NHL),
      and consists of the anti-CD20 murine monoclonal antibody, ibritumomab, covalently
      bound to the linker tiuxetan, which securely chelates the radioactive isotope
      90Y. Effective RIT demands a multidisciplinary approach to patient care, which
      places considerable emphasis on the role of the nurse. This review explores the
      role of the nurse in 90Y-ibritumomab tiuxetan therapy.

PMID- 15154743
TI  - Structure Elucidator: a versatile expert system for molecular structure
      elucidation from 1D and 2D NMR data and molecular fragments.
AB  - StrucEluc is an expert system that allows the computer-assisted elucidation of
      chemical structures based on the inputs of a series of spectral data including 1D
      and 2D NMR and mass spectra. The system has been enabled to allow a chemist to
      utilize fragments stored in a fragment database as well as user-defined fragments
      submitted by the chemist in the structure elucidation process. The association of
      fragments in this way has been shown to dramatically speed up the process of
      structure generation from 2D NMR data and has helped to minimize or eliminate the
      need for user intervention thereby further enabling the vision of automated
      elucidation. The use of fragments has frequently transformed very difficult 2D
      NMR elucidation challenges into easily solvable tasks. A strategy to utilize
      molecular fragments has been developed and optimized based on specific
      challenging examples. This strategy will be described here using real world
      examples. Experience gained by solving more than 150 structure elucidation
      problems from a variety of literature sources is also reviewed in this work.

PMID- 15154744
TI  - Virtual screening using protein-ligand docking: avoiding artificial enrichment.
AB  - This study addresses a number of topical issues around the use of protein-ligand
      docking in virtual screening. We show that, for the validation of such methods,
      it is key to use focused libraries (containing compounds with one-dimensional
      properties, similar to the actives), rather than "random" or "drug-like"
      libraries to test the actives against. We also show that, to obtain good
      enrichments, the docking program needs to produce reliable binding modes. We
      demonstrate how pharmacophores can be used to guide the dockings and improve
      enrichments, and we compare the performance of three consensus-ranking protocols
      against ranking based on individual scoring functions. Finally, we show that
      protein-ligand docking can be an effective aid in the screening for weak,
      fragment-like binders, which has rapidly become a popular strategy for hit
      identification. All results presented are based on carefully constructed virtual
      screening experiments against four targets, using the protein-ligand docking
      program GOLD.

PMID- 15154745
TI  - Comparing the quality and predictiveness between 3D QSAR models obtained from
      manual and automated alignment.
AB  - A set of 113 flexible cyclic urea inhibitors of human immunodeficiency virus
      protease (HIV-1 PR) was used to compare the quality and predictive power of CoMFA
      and CoMSIA models for manually or automatically aligned inhibitor set. Inhibitors
      that were aligned automatically with molecular docking were in agreement with
      information obtained from existing X-ray structures. Both alignment methods
      produced statistically significant CoMFA and CoMSIA models, with the best q(2)
      value being 0.649 and the best predictive r(2) being 0.754. The manual alignment
      gave statistically higher values, whereas the automated alignment gave more
      robust models for predicting the activities of an external inhibitor set. Both
      models utilized similar amino acids in the HIV-1 PR active site, supporting the
      idea that hydrogen bonds form between an inhibitor and the backbone carbonyl
      oxygens of Gly48 and Gly48' and also the backbone NH group of Asp30, Gly48,
      Asp29', and Gly48' of the enzyme. These results suggest that an automated
      inhibitor alignment can yield predictive 3D QSAR models that are well comparable
      to manual methods. Thus, an automated alignment method in creating 3D QSAR models
      is encouragable when a well-characterized structure of the target protein is
      available.

PMID- 15154746
TI  - Statistically based reduced representation of amino acid side chains.
AB  - Preferred conformations of amino acid side chains have been well established
      through statistically obtained rotamer libraries. Typically, these provide bond
      torsion angles allowing a side chain to be traced atom by atom. In cases where it
      is desirable to reduce the complexity of a protein representation or prediction,
      fixing all side-chain atoms may prove unwieldy. Therefore, we introduce a general
      parametrization to allow positions of representative atoms (in the present study,
      these are terminal atoms) to be predicted directly given backbone atom
      coordinates. Using a large, culled data set of amino acid residues from high
      resolution protein crystal structures, anywhere from 1 to 7 preferred
      conformations were observed for each terminal atom of the non-glycine residues.
      Side-chain length from the backbone C(alpha) is one of the parameters determined
      for each conformation, which should itself be useful. Prediction of terminal
      atoms was then carried out for a second, nonredundant set of protein structures
      to validate the data set. Using four simple probabilistic approaches, the Monte
      Carlo style prediction of terminal atom locations given only backbone coordinates
      produced an average root mean-square deviation (RMSD) of approximately 3 A from
      the experimentally determined terminal atom positions. With prediction using
      conditional probabilities based on the side-chain chi(1) rotamer, this average
      RMSD was improved to 1.74 A. The observed terminal atom conformations therefore
      provide reasonable and potentially highly accurate representations of side-chain
      conformation, offering a viable alternative to existing all-atom rotamers for any
      case where reduction in protein model complexity, or in the amount of data to be
      handled, is desired. One application of this representation with strong potential
      is the prediction of charge density in proteins. This would likely be especially
      valuable on protein surfaces, where side chains are much less likely to be fixed
      in single rotamers. Prediction of ensembles of structures provides a method to
      determine the probability density of charge and atom location; such a prediction
      is demonstrated graphically.

PMID- 15154747
TI  - Chirality codes and molecular structure.
AB  - Some time ago a structure-descriptor, named "chirality code", was put forward [J.
      Chem. Inf. Comput. Sci. 2001, 41, 369-375], aimed at distinguishing between
      enantiomers. The chirality code is a sequence of (typically 100) numbers, being
      equal to the value of a certain "chirality function" at equidistant points within
      a chosen interval. For molecules of moderate size the chirality function has
      thousands of peaks (maxima and minima), one for each quartet of atoms. Therefore
      it looks as if the chirality code cannot provide a faithful representation of the
      chirality function and thus a faithful representation of the molecular structure.
      We now show that functional groups present in the molecule result in clusters of
      near-lying and partially overlapping peaks, whose position in the chirality code
      is characteristic for the particular functional group. This enables a sound
      structural interpretation of the chirality code.

PMID- 15154748
TI  - SURFCOMP: a novel graph-based approach to molecular surface comparison.
AB  - Analysis of the distributions of physicochemical properties mapped onto molecular
      surfaces can highlight important similarities or differences between compound
      classes, contributing to rational drug design efforts. Here we present an
      approach that uses maximal common subgraph comparison and harmonic shape image
      matching to detect locally similar regions between two molecular surfaces
      augmented with properties such as the electrostatic potential or lipophilicity.
      The complexity of the problem is reduced by a set of filters that implement
      various geometric and physicochemical heuristics. The approach was tested on
      dihydrofolate reductase and thermolysin inhibitors and was shown to recover the
      correct alignments of the compounds bound in the active sites.

PMID- 15154749
TI  - Theoretical prediction of partition coefficients via molecular electrostatic and
      electronic properties.
AB  - Previously published methods for calculation of Abraham's polarity/polarizability
      and hydrogen bond acidity and basicity descriptors are validated for their
      ability to predict the various partition coefficients of 80 challenging
      molecules. As well as this indirect validation, accurate log P predictions are
      shown to be possible by using directly the fundamental molecular properties used
      in the calculation of descriptors. From a general point of view, the van der
      Waals and hydrogen bond interactions present between the solute and the
      water/solvent system can be represented by charge-based interactions, which are
      partitioned into a positive and a negative term (Sigma(T)V(Max) and
      Sigma(T)V(Min)), dipole-based interactions (mu) and induced dipole-based
      interactions (alpha); further stabilization is possible if solute and solvent
      densities come into contact and overlap (Sigma(T)E). A discussion is opened on
      the possibility to extend this set to describe systems with electron
      donor/acceptor interactions other than hydrogen bonding.

PMID- 15154750
TI  - De novo generation of molecular structures using optimization to select graphs on
      a given lattice.
AB  - A recurrent problem in organic chemistry is the generation of new molecular
      structures that conform to some predetermined set of structural constraints that
      are imposed in an endeavor to build certain required properties into the newly
      generated structure. An example of this is the pharmacophore model, used in
      medicinal chemistry to guide de novo design or selection of suitable structures
      from compound databases. We propose here a method that efficiently links up a
      selected number of required atom positions while at the same time directing the
      emergent molecular skeleton to avoid forbidden positions. The linkage process
      takes place on a lattice whose unit step length and overall geometry is designed
      to match typical architectures of organic molecules. We use an optimization
      method to select from the many different graphs possible. The approach is
      demonstrated in an example where crystal structures of the same (in this case
      rigid) ligand complexed with different proteins are available.

PMID- 15154751
TI  - Induction of decision trees via evolutionary programming.
AB  - Decision trees have been used extensively in cheminformatics for modeling various
      biochemical endpoints including receptor-ligand binding, ADME properties,
      environmental impact, and toxicity. The traditional approach to inducing decision
      trees based upon a given training set of data involves recursive partitioning
      which selects partitioning variables and their values in a greedy manner to
      optimize a given measure of purity. This methodology has numerous benefits
      including classifier interpretability and the capability of modeling nonlinear
      relationships. The greedy nature of induction, however, may fail to elucidate
      underlying relationships between the data and endpoints. Using evolutionary
      programming, decision trees are induced which are significantly more accurate
      than trees induced by recursive partitioning. Furthermore, when assessed on
      previously unseen data in a 10-fold cross-validated manner, evolutionary
      programming induced trees exhibit a significantly higher accuracy on previously
      unseen data. This methodology is compared to single-tree and multiple-tree
      recursive partitioning in two domains (aerobic biodegradability and
      hepatotoxicity) and shown to produce less complex classifiers with average
      increases in predictive accuracy of 5-10% over the traditional method.

PMID- 15154752
TI  - Assessment of docking poses: interactions-based accuracy classification (IBAC)
      versus crystal structure deviations.
AB  - Six docking programs (FlexX, GOLD, ICM, LigandFit, the Northwestern University
      version of DOCK, and QXP) were evaluated in terms of their ability to reproduce
      experimentally observed binding modes (poses) of small-molecule ligands to
      macromolecular targets. The accuracy of a pose was assessed in two ways: First,
      the RMS deviation of the predicted pose from the crystal structure was
      calculated. Second, the predicted pose was compared to the experimentally
      observed one regarding the presence of key interactions with the protein. The
      latter assessment is referred to as interactions-based accuracy classification
      (IBAC). In a number of cases significant discrepancies were found between IBAC
      and RMSD-based classifications. Despite being more subjective, the IBAC proved to
      be a more meaningful measure of docking accuracy in all these cases.

PMID- 15154753
TI  - Novel scoring functions comprising QXP, SASA, and protein side-chain entropy
      terms.
AB  - Novel scoring functions that predict the affinity of a ligand for its receptor
      have been developed. They were built with several statistical tools (partial
      least squares, genetic algorithms, neural networks) and trained on a data set of
      100 crystal structures of receptor-ligand complexes, with affinities spanning 10
      log units. The new scoring functions contain both descriptors generated by the
      QXP docking program and new descriptors that were developed in-house. These new
      descriptors are based on solvent accessible surface areas and account for
      conformational entropy changes and desolvation effects of both ligand and
      receptor upon binding. The predictive r(2) values for a test set of 24 complexes
      are in the 0.712-0.741 range and RMS prediction errors in the 1.09-1.16 log K(d)
      range. Inclusion of the new descriptors led to significant improvements in
      affinity prediction, compared to scoring functions based on QXP descriptors
      alone. However, the QXP descriptors by themselves perform better in binding mode
      prediction. The performance of the linear models is comparable to that of the
      neural networks. The new functions perform very well, but they still need to be
      validated as universal tools for the prediction of binding affinity.

PMID- 15154754
TI  - Clustering files of chemical structures using the fuzzy k-means clustering
      method.
AB  - This paper evaluates the use of the fuzzy k-means clustering method for the
      clustering of files of 2D chemical structures. Simulated property prediction
      experiments with the Starlist file of logP values demonstrate that use of the
      fuzzy k-means method can, in some cases, yield results that are superior to those
      obtained with the conventional k-means method and with Ward's clustering method.
      Clustering of several small sets of agrochemical compounds demonstrate the
      ability of the fuzzy k-means method to highlight multicluster membership and to
      identify outlier compounds, although the former can be difficult to interpret in
      some cases.

PMID- 15154755
TI  - Ab initio vs molecular mechanics thermochemistry: homocubanes.
AB  - The standard enthalpies of formation and strain energies for a series of
      homocubanes have been investigated by high-level ab initio G3(MP2)/B3LYP method.
      The relative stabilities of isomers are discussed. The comparison is made between
      the results of ab initio and molecular mechanics methods with the aim of
      assessing their performances. The usefulness of high-level calculations for
      generating thermochemical databases of relatively large molecules (e.g.
      C(11)H(14)) was also demonstrated.

PMID- 15154756
TI  - Continuous wavelet transform applied to removing the fluctuating background in
      near-infrared spectra.
AB  - A novel method based on continuous wavelet transform (CWT) was proposed as a
      preprocessing tool for the near-infrared (NIR) spectra. Due to the property of
      the vanishing moments of the wavelet, the fluctuating background of the NIR
      spectra can be successfully removed through convolution of the spectra with an
      appropriate wavelet function. The vanishing moments of a wavelet and the scale
      parameter are two key factors that govern the result of the background
      elimination. The result of its application to both the simulated spectra and the
      NIR spectra of tobacco samples demonstrates that CWT is a competitive tool for
      removing fluctuating background in spectra.

PMID- 15154757
TI  - Prediction of the formulation dependence of the glass transition temperatures of
      amine-epoxy copolymers using a QSPR based on the AM1 method.
AB  - A designer Quantitative Structure-Property Relationship, based upon molecular
      properties calculated using the AM1 semiempirical quantum mechanical method, was
      developed to predict the glass transition temperature of amine-cured epoxy resins
      based on the diglycidyl ether of bisphenol A. The QSPR (R2 = 0.9977) was
      generated using the regression analysis program, COmprehensive DEscriptors for
      Structural and Statistical Analysis. By applying an ad hoc treatment based on the
      elementary probability theory to the quantitative structure-property relationship
      analysis a method was developed for computing bulk polymer glass transition
      temperatures for stoichiometric and nonstoichiometric monomeric formulations. A
      model polymer was synthesized and found to validate our model predictions.

PMID- 15154758
TI  - Feature selection for descriptor based classification models. 1. Theory and GA
      SEC algorithm.
AB  - The paper describes different aspects of classification models based on molecular
      data sets with the focus on feature selection methods. Especially model quality
      and avoiding a high variance on unseen data (overfitting) will be discussed with
      respect to the feature selection problem. We present several standard approaches
      and modifications of our Genetic Algorithm based on the Shannon Entropy Cliques
      (GA-SEC) algorithm and the extension for classification problems using boosting.

PMID- 15154759
TI  - Feature selection for descriptor based classification models. 2. Human intestinal
      absorption (HIA).
AB  - We show that the topological polar surface area (TPSA) descriptor and the radial
      distribution function (RDF) applied to electronic and steric atom properties,
      like the conjugated electrotopological state (CETS), are the most relevant
      features/descriptors for predicting the human intestinal absorption (HIA) out of
      a large set of 2934 features/descriptors. A HIA data set with 196 molecules with
      measured HIA values and 2934 features/descriptors were calculated using JOELib
      and MOE. We used an adaptive boosting algorithm to solve the binary
      classification problem (AdaBoost.M1) and Genetic Algorithms based on Shannon
      Entropy Cliques (GA-SEC) variants as hybrid feature selection algorithms. The
      selection of relevant features was applied with respect to the generalization
      ability of the classification model, avoiding a high variance for unseen
      molecules (overfitting).

PMID- 15154760
TI  - Structure-based predictions of 1H NMR chemical shifts using feed-forward neural
      networks.
AB  - Feed-forward neural networks were trained for the general prediction of 1H NMR
      chemical shifts of CH(n) protons in organic compounds in CDCl3. The training set
      consisted of 744 1H NMR chemical shifts from 120 molecular structures. The method
      was optimized in terms of selected proton descriptors (selection of variables),
      the number of hidden neurons, and integration of different networks in ensembles.
      Predictions were obtained for an independent test set of 952 cases with a mean
      average error of 0.29 ppm (0.20 ppm for 90% of the cases). The results were
      significantly better than those obtained with counterpropagation neural networks.

PMID- 15154761
TI  - The impact of available experimental data on the prediction of 1H NMR chemical
      shifts by neural networks.
AB  - Two different ways were explored to incorporate new available experimental data
      into previously trained ensembles of feed-forward neural networks, for the
      structure-based prediction of (1)H NMR chemical shifts of organic compounds. One
      approach used the new data as the memory of an associative neural network (ASNN)
      system. For an independent prediction set of 952 cases, a mean average error of
      0.19 ppm was achieved (0.13 ppm for 90% of the cases). This approach
      advantageously avoids retraining the networks, and the predictions compared
      favorably with those obtained by available commercial software packages.
      Excellent predictions could also be achieved by retraining the networks with the
      new data, but only if the training sets were selected so as to be balanced or if
      the retraining started with the weights of the previously trained networks.

PMID- 15154762
TI  - Study of the quantitative structure-mobility relationship of carboxylic acids in
      capillary electrophoresis based on support vector machines.
AB  - The support vector machines (SVM), as a novel type of learning machine, were used
      to develop a quantitative structure-mobility relationship (QSMR) model of 58
      aliphatic and aromatic carboxylic acids based on molecular descriptors calculated
      from the structure alone. Multiple linear regression (MLR) and radial basis
      function neural networks (RBFNNs) were also utilized to construct the linear and
      the nonlinear model to compare with the results obtained by SVM. The root-mean
      square errors in absolute mobility predictions for the whole data set given by
      MLR, RBFNNs, and SVM were 1.530, 1.373, and 0.888 mobility units (10(-5) cm(2) S(
      1) V(-1)), respectively, which indicated that the prediction result agrees well
      with the experimental values of these compounds and also revealed the superiority
      of SVM over MLR and RBFNNs models for the prediction of the absolute mobility of
      carboxylic acids. Moreover, the models we proposed could also provide some
      insight into what structural features are related to the absolute mobility of
      aliphatic and aromatic carboxylic acids.

PMID- 15154763
TI  - On the aggregation state and QSPR models. The solubility of herbicides as a case
      study.
AB  - The goal of this article is to stress the importance of considering the phase in
      QSPR studies. It is found that the phase plays a fundamental role in the QSPR
      models from both a statistical and a physical point of view. From a statistical
      point of view, it is observed that the predictive performance drops drastically
      when the QSPR model, obtained for a given phase, is used to predict the
      solubility of the same set of compounds but in another phase. From a physical
      point of view, when the compounds in the training set are in different phases,
      the physical interpretation of the descriptors involved in the model is obscured
      because the descriptors which appear in the correlation equation are a sort of
      average encoding the different physical mechanisms underlying the property. It is
      shown that the use of compounds in the same phase, instead, allows a more
      transparent physical interpretation of the descriptors involved in the model and,
      at the same time, improves the statistics of the models.

PMID- 15154764
TI  - Process-driven information management system at a biotech company: concept and
      implementation.
AB  - While established pharmaceutical companies have chemical information systems in
      place to manage their compounds and the associated data, new startup companies
      need to implement these systems from scratch. Decisions made early in the design
      phase usually have long lasting effects on the expandability, maintenance effort,
      and costs associated with the information management system. Careful analysis of
      work and data flows, both inter- and intradepartmental, and identification of
      existing dependencies between activities are important. This knowledge is
      required to implement an information management system, which enables the
      research community to work efficiently by avoiding redundant registration and
      processing of data and by timely provision of the data whenever needed. This
      paper first presents the workflows existing at Anadys, then ARISE, the research
      information management system developed in-house at Anadys. ARISE was designed to
      support the preclinical drug discovery process and covers compound registration,
      analytical quality control, inventory management, high-throughput screening,
      lower throughput screening, and data reporting.

PMID- 15154765
TI  - Predictive models for aquatic toxicity of aldehydes designed for various model
      chemistries.
AB  - Predictive models for the aquatic toxicity of aldehydes were designed for a set
      of 50 aromatic or aliphatic compounds containing at least one aldehyde group, for
      which the acute toxicity data for the fathead minnow (Pimephales promelas) are
      available (96 h test assessing 50% lethal waterborne concentration). The
      molecular descriptors were based on calculations with various semiempirical or ab
      initio model chemistries. The resulting four-parameter models were evaluated
      according to the correlation coefficients R(2). The best predictive model was
      obtained with the HF/STO-3G model chemistry (R(2) = 0.868), while the models
      designed for descriptors based on ab initio calculations of higher level showed a
      slightly worse predictivity (the HF/3-21G(d) based model R(2) = 0.800, the HF/6
      31G(d) based model R(2) = 0.808, the B3LYP/6-31G(d,p) based model R(2) = 0.812).
      With the semiempirical methods a good predictivity was observed with the PM3
      based model (R(2) = 0.811) and the AM1 based model (R(2) = 0.791), but the MNDO
      based model showed the worst predictivity (R(2) = 0.760). In all ab initio models
      and the PM3 model very similar descriptors were involved. The importance of the
      descriptor logarithm of the partition coefficient logP for toxicity prediction
      was confirmed. Additionally, the descriptors encoding the negatively charged
      molecular surface area, hydrogen bonding molecular surface area, and reactivity
      of aldehyde group were identified as essential for the toxicity prediction of
      aldehydes.

PMID- 15154766
TI  - QSPR study on the bioconcentration factors of nonionic organic compounds in fish
      by characteristic root index and semiempirical molecular descriptors.
AB  - The characteristic root index (CRI) was modeled together with four semiempirical
      molecular descriptors, namely-energies of the highest occupied and the lowest
      unoccupied molecular orbital (E(HOMO) and E(LUMO)), heat of formation
      (DeltaH(f)), and dipole moment (micro)-to predict the fish bioconcentration
      factor (BCF) of 122 nonionic organic compounds. The best fit equation found by
      "forward multiple linear regression" showed that the topology based CRI was the
      most important parameter. The addition of quantum chemical descriptors made only
      a slight improvement in the predictive capability of the Quantitative Structure
      Property Relationship (QSPR) model. The CRI was followed by E(HOMO). A two
      parameter equation with a correlation coefficient of r = 0.921 was obtained for a
      diverse set of nonionic organic chemicals. Statistical robustness of the
      developed model was validated by modified jackknife tests where random deletion
      of a class of compounds and specific deletion of a set of compounds were both
      performed. The predictive accuracy of the proposed model was compared with the
      commonly used K(ow) model and recently published studies in which BCF models were
      developed. Particular emphasis has been made to clearly define the boundaries for
      the application of the alternative developed model as well as the quality of
      estimates.

PMID- 15154767
TI  - SVM-based feature selection for characterization of focused compound collections.
AB  - Artificial neural networks, the support vector machine (SVM), and other machine
      learning methods for the classification of molecules are often considered as a
      "black box", since the molecular features that are most relevant for a given
      classifier are usually not presented in a human-interpretable form. We report on
      an SVM-based algorithm for the selection of relevant molecular features from a
      trained classifier that might be important for an understanding of ligand
      receptor interactions. The original SVM approach was extended to allow for
      feature selection. The method was applied to characterize focused libraries of
      enzyme inhibitors. A comparison with classical Kolmogorov-Smirnov (KS)-based
      feature selection was performed. In most of the applications the SVM method
      showed sustained classification accuracy, thereby relying on a smaller number of
      molecular features than KS-based classifiers. In one case both methods produced
      comparable results. Limiting the calculation of descriptors to only the most
      relevant ones for a certain biological activity can also be used to speed up high
      throughput virtual screening.

PMID- 15154768
TI  - ESOL: estimating aqueous solubility directly from molecular structure.
AB  - This paper describes a simple method for estimating the aqueous solubility (ESOL-
      Estimated SOLubility) of a compound directly from its structure. The model was
      derived from a set of 2874 measured solubilities using linear regression against
      nine molecular properties. The most significant parameter was calculated
      logP(octanol), followed by molecular weight, proportion of heavy atoms in
      aromatic systems, and number of rotatable bonds. The model performed consistently
      well across three validation sets, predicting solubilities within a factor of 5-8
      of their measured values, and was competitive with the well-established "General
      Solubility Equation" for medicinal/agrochemical sized molecules.

PMID- 15154769
TI  - Classification of dopamine antagonists using TFS-based artificial neural network.
AB  - In the former work, the authors proposed the Topological Fragment Spectral (TFS)
      method as a tool for the description of the topological structure profile of a
      molecule. This paper describes the TFS-based artificial neural network (TFS/ANN)
      approach for the classification and the prediction of pharmacological active
      classes of chemicals. Dopamine antagonists of 1227 that interact with different
      types of receptors (D1, D2, D3, and D4) were used for the training. The TFS/ANN
      successfully classified 89% of the drugs into their own active classes. Then, the
      trained model was used for predicting the class of unknown compounds. For the
      prediction set of 137 drugs that were not included in the training set, the
      TFS/ANN model predicted 111 (81%) drugs of them into their own active classes
      correctly.

PMID- 15154770
TI  - Development and use of hydrophobic surface area (HSA) descriptors for computer
      assisted quantitative structure-activity and structure-property relationship
      studies.
AB  - A new series of 25 whole-molecule molecular structure descriptors are proposed.
      The new descriptors are termed Hydrophobic Surface Area, or HSA descriptors, and
      are designed to capture information regarding the structural features responsible
      for hydrophobic and hydrophilic intermolecular interactions. The utility of the
      HSAs in capturing this type of information is demonstrated using two properties
      that have a known hydrophobic component. The first study involves the modeling of
      the inhibition of Gram-positive bacteria cell growth of a series of biarylamides.
      The second application involves the study of the blood-brain barrier penetration
      of a diverse series of drug molecules. In both cases, the HSAs are shown to
      effectively capture information related to the hydrophobic components of these
      two properties. Additional evaluation of the new class of descriptors shows them
      to be unique in their ability to measure hydrophobic features among a diverse set
      of conventional structural descriptors. The HSAs are evaluated regarding their
      sensitivity to conformational changes and are found to be similar in that regard
      to other widely used molecular descriptors.

PMID- 15154771
TI  - SCSA code: applications on the cyclopeptide renieramide.
AB  - SCSA is an algorithm designed to get information on molecular conformational
      properties. The most stable conformers are determined by the homemade SCSA code,
      performing a multistep systematic conformational search, which involves energy
      and structure quantum chemical optimizations at low-level and high-level. The
      SCSA method was employed to analyze the conformational space of the in vacuo
      cyclopeptide renieramide at AM1 and B3LYP/6-31G(d) levels. Calculations at B3LYP
      level of the GIAO (13)C NMR chemical shifts were also performed on the final
      conformers. In fact, to validate the conformational search results experimental
      and calculated (13)C NMR spectra of renieramide were compared. Slight
      disagreements observed between experimental and calculated spectra could be
      attributed to solute-solvent interactions, which were not taken into account in
      the algorithm proposed here.

PMID- 15154772
TI  - Artificial neural networks and linear discriminant analysis: a valuable
      combination in the selection of new antibacterial compounds.
AB  - A set of topological descriptors has been used to discriminate between
      antibacterial and nonantibacterial drugs. Topological descriptors are simple
      integers calculated from the molecular structure represented in SMILES format.
      The methods used for antibacterial activity discrimination were linear
      discriminant analysis (LDA) and artificial neural networks of a multilayer
      perceptron (MLP) type. The following plot frequency distribution diagrams were
      used: a function of the number of drugs within a value interval of the
      discriminant function and the output value of the neural network versus these
      values. Pharmacological distribution diagrams (PDD) were used as a visualizing
      technique for the identification of antibacterial agents. The results confirmed
      the discriminative capacity of the topological descriptors proposed. The combined
      use of LDA and MLP in the guided search and the selection of new structures with
      theoretical antibacterial activity proved highly effective, as shown by the in
      vitro activity and toxicity assays conducted.

PMID- 15154773
TI  - Theoretical scales of hydrogen bond acidity and basicity for application in
      QSAR/QSPR studies and drug design. Partitioning of aliphatic compounds.
AB  - Phenomenological analysis of existing hydrogen bond (HB) donor and acceptor
      scales and apparent physical considerations have enabled the establishment of new
      quantitative scales of hydrogen bond basicity and acidity. Chemical structures
      represented by molecular graphs and the orbital electronegativities of Hinze and
      Jaffe are utilized as an input data. The scales obtained correlate well with
      several experimental solvent polarity scales such as and, pK(HB), and E(T)(30).
      To demonstrate the applicability of the new quantities, we have applied them to
      seven equilibrium partitioning data sets: octanol-water, hexadecane-water,
      chloroform-water, gas-water, gas-octanol, gas-hexadecane, and gas-chloroform
      partition coefficients. The hydrogen bond descriptors when supplemented by a
      cavity-forming term and a dipolarity term show high performance in correlations
      of the partition coefficients of aliphatic compounds. These new HB descriptors
      can be used in studying hydrogen bonding and fluid phase equilibria as well as
      scoring functions in ligand docking and descriptors in ADME evaluations.

PMID- 15154774
TI  - Spectral pattern recognition using self-organizing MAPS.
AB  - A Kohonen neural network is an iterative technique used to map multivariate data.
      The network is able to learn and display the topology of the data. Self
      organizing maps have advantages as well as drawbacks when compared to principal
      component plots. One advantage is that data preprocessing is usually minimal.
      Another is that an outlier will only affect one map unit and its neighborhood.
      However, outliers can have a drastic and disproportionate effect on principal
      component plots. Removing them does not always solve the problem for as soon as
      the worst outliers are deleted, other data points may appear in this role. The
      advantage of using self-organizing maps for spectral pattern recognition is
      demonstrated by way of two studies recently completed in our laboratory. In the
      first study, Raman spectroscopy and self-organizing maps were used to
      differentiate six common household plastics by type for recycling purposes. The
      second study involves the development of a potential method to differentiate
      acceptable lots from unacceptable lots of avicel using diffuse reflectance near
      infrared spectroscopy and self-organizing maps.

PMID- 15154775
TI  - Automated drawing of structural molecular formulas under constraints.
AB  - In this paper, we present a new algorithm for automated drawing of 2D structural
      formulas of molecules. The algorithm is based on the classical scheme of a
      drawing queue placing the molecular fragments in a sequential way. We extend the
      concept of so-called prefabricated units developed for complex ring systems to
      automatically created drawing units for chains and rings which will then be
      assembled in a sequential fashion. The approach is fast and can be naturally
      extended to the problem of drawing molecules with common core structures. Further
      on, we present an algorithm that allows the drawing of 2D structural formulas
      under directional constraints assigned to a subset of bonds. Since no numerical
      optimization is necessary, the algorithm creates drawings of small organic
      molecules on the order of 500 structures per second. The new algorithm is
      relevant for all kinds of prediction and analysis software presenting a large
      number of probably similar molecular structures to the user of the software.

PMID- 15154776
TI  - A graph-based genetic algorithm and its application to the multiobjective
      evolution of median molecules.
AB  - In this paper we propose a novel graph-based genetic algorithm for the evolution
      of novel molecular graphs from a predefined set of elements or molecular
      fragments with an external objective function. A brief overview of existing
      genetic algorithm approaches in molecular design is provided followed by a
      description of our approach. The paper continues to suggest a novel application
      of this program to the multiobjective evolution of median molecules that are
      structurally representative of a set of objective molecules. We conclude with a
      summary of our initial results along with a discussion of a variety of
      improvements and applications of our approach.

PMID- 15154777
TI  - Using surrogate modeling in the prediction of fibrinogen adsorption onto polymer
      surfaces.
AB  - We present a Surrogate (semiempirical) Model for prediction of protein adsorption
      onto the surfaces of biodegradable polymers that have been designed for tissue
      engineering applications. The protein used in these studies, fibrinogen, is known
      to play a key role in blood clotting. Therefore, fibrinogen adsorption dictates
      the performance of implants exposed to blood. The Surrogate Model combines
      molecular modeling, machine learning and an Artificial Neural Network. This novel
      approach includes an accounting for experimental error using a Monte Carlo
      analysis. Briefly, measurements of human fibrinogen adsorption were obtained for
      45 polymers. A total of 106 molecular descriptors were generated for each
      polymer. Of these, 102 descriptors were computed using the Molecular Operating
      Environment (MOE) software based upon the polymer chemical structures, two
      represented different monomer types, and two were measured experimentally. The
      Surrogate Model was developed in two stages. In the first stage, the three
      descriptors with the highest correlation to adsorption were determined by
      calculating the information gain of each descriptor. Here a Monte Carlo approach
      enabled a direct assessment of the effect of the experimental uncertainty on the
      results. The three highest-ranking descriptors, defined as those with the highest
      information gain for the sample set, were then selected as the input variables
      for the second stage, an Artificial Neural Network (ANN) to predict fibrinogen
      adsorption. The ANN was trained using one-half of the experimental data set (the
      training set) selected at random. The effect of experimental error on predictive
      capability was again explored using a Monte Carlo analysis. The accuracy of the
      ANN was assessed by comparison of the predicted values for fibrinogen adsorption
      with the experimental data for the remaining polymers (the validation set). The
      mean value of the Pearson correlation coefficient for the validation data sets
      was 0.54 +/- 0.12. The average root-mean-square (relative) error in prediction
      for the validation data sets is 38%. This is an order of magnitude less than the
      range of experimental values (i.e., 366%) and compares favorably with the average
      percent relative standard deviation of the experimental measurements (i.e.,
      17.9%). The effects of each of the user-defined parameters in the ANN were
      explored. None were observed to have a significant effect on the results. Thus,
      the Surrogate Model can be used to accurately and unambiguously identify polymers
      whose fibrinogen absorption is at the limits of the range (i.e., low or high)
      which is an essential requirement for assessing polymers for regenerative tissue
      applications.

PMID- 15154778
TI  - Determination of Abraham solute parameters from molecular structure.
AB  - The Abraham solute parameters are well-known factors for the quantitative
      description of solute/solvent interactions. A quantitative structure-property
      relationship (QSPR) is reported for the E, S, A, and B parameters of a large set
      of 457 solutes, of very different chemical nature. The proposed models, derived
      from multilinear regression analysis (MLRA) and computational neural networks
      (CNN), contain five descriptors calculated solely from the molecular structure of
      compounds. Good correlations were obtained for the four parameters studied, and
      the corresponding values of R(2) and standard deviations are better or similar
      than those derived from other theoretical bases. All models were validated by
      external prediction sets. The proposed QSPR models, both by MLRA and CNN, contain
      analogous descriptors encoding similar information, that agree with the accepted
      physicochemical meaning of the Abraham parameters; however, some descriptors
      which encode information that is not associated with this physicochemical meaning
      are also included in the QSPR models.

PMID- 15154779
TI  - Discriminant function analyses of liver-specific carcinogens.
AB  - The ability to predict organ-specific carcinogenicity would aid FDA reviewers in
      evaluating new chemical applications. A NCTR liver cancer database (NCTRlcdb)
      containing 999 compounds has been developed with three sets of descriptors. The
      NCTRlcdb has Cerius2, Molconn-Z, and (13)C NMR descriptors for each compound.
      Each compound in the database was assigned a liver cancer or a nonliver cancer
      classification. Compounds within the NCTRlcdb were evaluated for liver-specific
      carcinogenicity using partial least squares principal component discriminant
      function (PLS-DF) modeling. PLS-DF models based on estimated a priori
      classification probabilities of 0.29 for liver cancer and 0.71 for noncancer
      yielded an overall predictability of 70.6% which was comprised of a liver cancer
      sensitivity of 18.8% and a noncancer specificity of 90.8%. PLS-DF models based on
      equal a priori classification probabilities, 0.50 for liver cancer and 0.5 for
      noncancer, yielded an overall predictability of 61.0% which was comprised of a
      liver cancer sensitivity of 50.5% and a noncancer specificity of 65.3%.

PMID- 15154780
TI  - Virtual screening for SARS-CoV protease based on KZ7088 pharmacophore points.
AB  - Pharmacophore modeling can provide valuable insight into ligand-receptor
      interactions. It can also be used in 3D (dimensional) database searching for
      potentially finding biologically active compounds and providing new research
      ideas and directions for drug-discovery projects. To stimulate the structure
      based drug design against SARS (severe acute respiratory syndrome), a
      pharmacophore search was conducted over 3.6 millions of compounds based on the
      atomic coordinates of the complex obtained by docking KZ7088 (a derivative of
      AG7088) to SARS CoV M(pro) (coronavirus main proteinase), as reportedly recently
      (Chou, K. C.; Wei, D. Q.; Zhong, W. Z. Biochem. Biophys. Res. Commun. 2003, 308,
      148-151). It has been found that, of the 3.6 millions of compounds screened,
      0.07% are with the score satisfying five of the six pharmacophore points.
      Moreover, each of the hit compounds has been evaluated for druggability according
      to 13 metrics based on physical, chemical, and structural properties. Of the
      0.07% compounds thus retrieved, 17% have a perfect score of 1.0; while 23% with
      one druggable rule violation, 13% two violations, and 47% more than two
      violations. If the criterion for druggability is set at a maximum allowance of
      two rule violations, we obtain that only about 0.03% of the compounds screened
      are worthy of further tests by experiments. These findings will significantly
      narrow down the search scope for potential compounds, saving substantial time and
      money. Finally, the featured templates derived from the current study will also
      be very useful for guiding the design and synthesis of effective drugs for SARS
      therapy.

PMID- 15154781
TI  - Impact of scoring functions on enrichment in docking-based virtual screening: an
      application study on renin inhibitors.
AB  - The docking program LigandFit/Cerius(2) has been used to perform shape-based
      virtual screening of databases against the aspartic protease renin, a target of
      determined three-dimensional structure. The protein structure was used in the
      induced fit binding conformation that occurs when renin is bound to the highly
      active renin inhibitor 1 (IC(50) = 2 nM). The scoring was calculated using
      several different scoring functions in order to get insight into the
      predictability of the magnitude of binding interactions. A database of 1000
      diverse and druglike compounds, comprised of 990 members of a virtual database
      generated by using the iLib diverse software and 10 known active renin
      inhibitors, was docked flexibly and scored to determine appropriate scoring
      functions. All seven scoring functions used (LigScore1, LigScore2, PLP1, PLP2,
      JAIN, PMF, LUDI) were able to retrieve at least 50% of the active compounds
      within the first 20% (200 molecules) of the entire test database. A hit rate of
      90% in the top 1.4% resulted using the quadruple consensus scoring of LigScore2,
      PLP1, PLP2, and JAIN. Additionally, a focused database was created with the iLib
      diverse software and used for the same procedure as the test database. Docking
      and scoring of the 990 focused compounds and the 10 known actives were performed.
      A hit rate of 100% in the top 8.4% resulted with use of the triple consensus
      scoring of PLP1, PLP2, and PMF. As expected, a ranking of the known active
      compounds within the focused database compared to the test database was observed.
      Adequate virtual screening conditions were derived empirically. They can be used
      for proximate docking and scoring application of compounds with putative renin
      inhibiting potency.

PMID- 15154782
TI  - Pseudoreceptor models and 3D-QSAR for imidazobenzodiazepines at GABA A/BzR
      subtypes alphaxbeta3gamma2 [x = 1-3, 5, and 6] via flexible atom receptor model.
AB  - Since benzodiazepines have been used widely in the treatment of anxiety,
      sleeplessness, and epilepsy, the receptor sites for the benzodiazepine are of
      prime importance. Quantitative structure-activity relationship (QSAR) studies and
      receptor modeling via Flexible Atom Receptor Model (FLARM) for the binding
      affinities of a series of imidazobenzodiazepines at five recombinant receptor
      subtypes were carried out successfully. The 3D-QSAR models for all five receptor
      subtypes were examined by a set of test set and demonstrated their high
      predictability for affinities of imidazobenzodiazepines at five receptor
      subtypes. The pseudoreceptors yielded by FLARM were compared to the united
      pharmacophore/receptor model. The result shows that two hydrogen bonds and other
      regions in the united pharmacophore/receptor model are presented in the
      pseudoreceptors, which demonstrates the receptor modeling capability of FLARM.
      The models and pseudoreceptors can help design high affinity ligands on the
      GABA(A)/BZ receptor and understand the GABA(A) receptor.

PMID- 15154783
TI  - GPCR-tailored pharmacophore pattern recognition of small molecular ligands.
AB  - The goal of our work was to differentiate between patterns, which are responsible
      for the activity of small molecular ligands binding to G-protein coupled
      receptors (GPCRs) and molecules, which are pharmacologically active on other
      target classes. Second the aim was to go one step further and analyze the
      chemical space occupied by GPCR active ligands itself, to distinguish between the
      actives of different subclasses or even cluster ligands for single receptors. To
      achieve these objectives, we have built a database of small, organic molecules,
      which bind to GPCRs. Once this crucial foundation for pattern recognition has
      been laid, we needed to find a descriptor, which is able to detect the compulsory
      features responsible for activity within a molecule. In this matter we found that
      the well accepted pharmacophore descriptor served us well. Finally we needed to
      find a method to display the clustering or separation of the specific ligands. We
      found that self-organizing maps (SOMs) perform excellently in this task. We
      herein present the analysis of the chemical space of active compounds, depending
      on their biological target, the GPCRs. We will also discuss the techniques used
      to create the chemical spaces. The findings can be applied and have an impact at
      various stages of the drug discovery process.

PMID- 15154784
TI  - Molecular design based on 3D pharmacophores. Applications to 5-HT7 receptors.
AB  - A definition of a pharmacophore for the 5-HT7 antagonists was carried out by
      searching the common chemical features of selective antagonists from the
      literature. A molecular design is described by analyzing the differences between
      this new pharmacophore and three other 3D serotonin pharmacophores previously
      described. This comparison led to the synthesis of a new series of potent 5-HT7
      antagonists.

PMID- 15154785
TI  - A study on the antipicornavirus activity of flavonoid compounds (flavones) by
      using quantum chemical and chemometric methods.
AB  - The AM1 semiempirical method is employed to calculate a set of molecular
      properties (variables) of 45 flavone compounds with antipicornavirus activity,
      and 9 new flavone molecules are used for an activity prediction study. Principal
      Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), Stepwise
      Discriminant Analysis (SDA), and K-Nearest Neighbor (KNN) are employed in order
      to reduce dimensionality and investigate which subset of variables should be more
      effective for classifying the flavone compounds according to their degree of
      antipicornavirus activity. The PCA, HCA, SDA, and KNN methods showed that the
      variables MR (molar refractivity), B(9) (bond order between C(9) and C(10)
      atoms), and B(25) (bond order between C(11) and R(7) atoms) are important
      properties for the separation between active and inactive flavone compounds, and
      this fact reveals that electronic and steric effects are relevant when one is
      trying to understand the interaction between flavone compounds with
      antipicornavirus activity and the biological receptor. In the activity prediction
      study, using the PCA, HCA, SDA, and KNN methodologies, three of the 9 new flavone
      compounds studied were classified as potentially active against picornaviruses.

PMID- 15154786
TI  - High-throughput modeling of human G-protein coupled receptors: amino acid
      sequence alignment, three-dimensional model building, and receptor library
      screening.
AB  - The current study describes the development of a computer package (GPCRmod) aimed
      at the high-throughput modeling of the therapeutically important family of human
      G-protein coupled receptors (GPCRs). GPCRmod first proposes a reliable alignment
      of the seven transmembrane domains (7 TMs) of most druggable human GPCRs based on
      pattern/motif recognition for each of the 7 TMs that are considered
      independently. It then converts the alignment into knowledge-based three
      dimensional (3-D) models starting from a set of 3-D backbone templates and two
      separate rotamer libraries for side chain positioning. The 7 TMs of 277 human
      GPCRs have been accurately aligned, unambiguously clustered in three different
      classes (rhodopsin-like, secretin-like, metabotropic glutamate-like), and
      converted into high-quality 3-D models at a remarkable throughput (ca. 3s/model).
      A 3-D GPCR target library of 277 receptors has consequently been setup. Its
      utility for "in silico" inverse screening purpose has been demonstrated by
      recovering among top scorers the receptor of a selective GPCR antagonist as well
      as the receptors of a promiscuous antagonist. The current GPCR target library
      thus constitutes a 3-D database of choice to address as soon as possible the
      "virtual selectivity" profile of any GPCR antagonist or inverse agonist in an
      early hit optimization process.

PMID- 15154787
TI  - Comparison of fingerprint-based methods for virtual screening using multiple
      bioactive reference structures.
AB  - Fingerprint-based similarity searching is widely used for virtual screening when
      only a single bioactive reference structure is available. This paper reviews
      three distinct ways of carrying out such searches when multiple bioactive
      reference structures are available: merging the individual fingerprints into a
      single combined fingerprint; applying data fusion to the similarity rankings
      resulting from individual similarity searches; and approximations to
      substructural analysis. Extended searches on the MDL Drug Data Report database
      suggest that fusing similarity scores is the most effective general approach,
      with the best individual results coming from the binary kernel discrimination
      technique.

PMID- 15154789
TI  - A monomeric nickel-dioxygen adduct derived from a nickel(I) complex and O2.
AB  - The nickel(I) complex [PhTt(Ad)]Ni(CO) (PhTt(Ad), phenyltris((1
      adamantylthio)methyl)borate) reacts with O(2) generating a 1:1 species identified
      as a side-on dioxygen adduct based on its spectroscopic properties as supported
      by DFT computational results and by its reactivity. The Ni EXAFS data are fit to
      a S(3)O(2) coordination environment with short Ni-O distances, 1.85 A. The brown
      complex displays a rhombic EPR signal with g values of 2.24, 2.19, 2.01. DFT and
      INDO/S-CI computations replicate the EXAFS and EPR features and suggest that 2 is
      a side-on [NiO(2)](+) complex with geometric and electronic properties that are
      best rationalized in terms of a highly covalent Ni(II)-superoxo description.
      [PhTt(Ad)]Ni(O(2)) oxidizes PPh(3) to OPPh(3), NO to NO(3)(-), and
      [PhTt(tBu)]Ni(CO) to the nonsymmetric [PhTt(Ad)]Ni(micro-O)(2)Ni[PhTt(tBu)]
      dimer.

PMID- 15154788
TI  - Halogenated aliphatic toxicity QSARs employing metabolite descriptors.
AB  - The toxic effects from exposure to halogenated hydrocarbons (HAs), which are
      produced in large amounts and used in a variety of applications, are well-known.
      Previously, QSARs for the toxicity of a series of HAs in vitro have been studied
      extensively. In this work, using a composite toxicity metric calculated from a
      set of five in vitro hepatotoxicity endpoints determined for 20 HAs, we find that
      QSARs derived using quantum descriptors calculated from the neutral HA species
      are statistically similar to QSARs calculated from HA metabolites. In most cases,
      QSARs derived using descriptors calculated from both neutral HAs and metabolites
      are statistically superior to those derived using either neutral-HA descriptors
      or metabolite descriptors. However, to properly utilize metabolite descriptors,
      multiple QSARs, each of which utilizes a set of HAs that form unique metabolites,
      must be derived and toxicity values calculated therefrom must be averaged. These
      average toxicity values agree better with experiment than those calculated from
      the neutral-HA QSARs.

PMID- 15154790
TI  - Synthesis of the new, cubane-like W3S4Co cluster core. Completion of the
      homologous series [(eta5-Cp')3M3S4Co(CO)] (M = Cr, Mo, W).
AB  - Reaction between the cluster salts [(eta(5)-Cp')(3)M(3)S(4)][pts] (M = Mo, W; Cp'
      = methylcyclopentadienyl; pts = p-toluenesulfonate) and [Co(2)(CO)(8)] yielded
      the electroneutral clusters [(eta(5)-Cp')(3)M(3)S(4)Co(CO)]. The molecular
      structure of [(eta(5)-Cp')(3)W(3)S(4)Co(CO)] was determined by single-crystal X
      ray diffraction methods. The unprecedented 60 electron W(3)S(4)Co cluster
      completes a homologous series of heterobimetallic clusters, [(eta(5)
      Cp')(3)M(3)S(4)Co(CO)] (M = Cr, Mo, W), containing a cubane-like core motif.

PMID- 15154791
TI  - Supramolecular stereocontrol of octahedral metal-centered chirality. Ligand
      modulation.
AB  - By associating chiral labile [FeL3](2+) complexes with TRISPHAT anions, a
      stereocontrol of the metal-centered chirality is feasible; the sense of the
      stereoselective induction and its magnitude strongly depends upon the structure
      of the diimine ligands (L: bpy, phen).

PMID- 15154792
TI  - Synthesis and structure of heterospin compounds based on the [Mn6(O)2Piv10]
      cluster unit and nitroxide.
AB  - Reaction of [Mn6(O)2Piv10(Thf)4].Thf with 2,4,4,5,5-pentamethyl-4,5-dihydro-1H
      imidazolyl-3-oxide-1-oxyl (NIT-Me) produces different heterospin compounds
      depending of the solvent used in the synthesis. Among the latter a new molecular
      magnet [Mn6(O)2Piv10(Thf)2(NIT-Me)Mn6(O)2Piv10(Thf)(CH2Cl2)(NIT-Me)] with Tc =
      3.5 K has been found.

PMID- 15154795
TI  - H2 activation in aqueous solution: formation of trans-[Fe(DMeOPrPE)2H(H2)]+ via
      the heterolysis of H2 in water.
AB  - The water-soluble iron phosphine complex trans-Fe(DMeOPrPE)(2)Cl(2) (DMeOPrPE =
      1,2-bis(bis(methoxypropyl)phosphino)ethane) reacts with H(2) in water to produce
      trans-[Fe(DMeOPrPE)(2)H(H(2))](+) and H(+). The product is a water-soluble eta(2)
      H(2) metal hydride complex, formed via the heterolysis of coordinated H(2) in
      water.

PMID- 15154793
TI  - A new class of (mu-eta2:eta2-disulfido)dicopper complexes: synthesis,
      characterization, and disulfido exchange.
AB  - Rare examples of (mu-eta2:eta2-disulfido)dicopper complexes have been prepared
      from Cu(I) and Cu(II) complexes of beta-diketiminate and anilido-imine supporting
      ligands. A novel byproduct derived from sulfur functionalization of the methine
      position of a beta-diketiminate ligand was identified. DFT calculations on
      [(LCu)2X2] (L = beta-diketiminate, X = O or S) complexes rationalize the absence
      of a bis(mu-sulfido)dicopper isomer, [Cu2(mu-S)2](2+), in the synthetic
      reactions, yet predict that a [Cu2(mu-S)2](0) core is a stable product of 2
      electron reduction of the [Cu2(mu-eta2:eta2-S2)](2+) unit. Exchange of the
      disulfido ligand was discovered upon reaction of a (mu-eta2:eta2
      disulfido)dicopper complex with a Cu(I) reagent.

PMID- 15154794
TI  - X-ray structure of physiological copper(II)-bis(L-histidinato) complex.
AB  - The isolation and the X-ray crystal structure of physiological copper(II)-L
      histidine complex are reported. The neutral five-coordinate complex shows
      distorted square pyramidal geometry with bidentate and tridentate L-histidine
      ligands. The basic character of the pendent imidazole group and H-bonding
      interactions of bidentate L-histidine ligand are important for copper transport.
      The unique structural features help explain the origin of its thermodynamic
      stability and kinetic reactivity in human blood along with the ternary copper(II)
      amino acid complexes. The role of L-histidine in interaction with copper(II)
      albumin, in cellular uptake of copper, and in treatment of Menkes disease can be
      studied using these results.

PMID- 15154796
TI  - Structural analysis of the conformational flexibility of tris(pyrazolyl)borate
      ligands and their analogues.
AB  - Database analysis and molecular mechanics were used to determine the
      conformational flexibility of tridentate scorpionate ligands. The
      tris(pyrazolyl)methane and tris(pyrazolyl)borate ligands act like molecular
      vises, opening their tripodal structure for larger metals and closing around
      smaller metal ions. Tris(3-tert-butylpyrazolyl)methane has significant preference
      for larger metal ions than its unsubstituted parent compound.
      Tris(pyrazolyl)methanes and tris(pyrazolyl)borates have similar conformational
      flexibilities. Placing sterically hindered groups on the central carbon or boron
      has only a minor effect on the geometry of the tris(pyrazolyl)methanes and
      tris(pyrazolyl)borates. However, it does influence the flexibility of the
      ligands, particularly when they have to open far from their ideal geometry, which
      commonly occurs.

PMID- 15154797
TI  - Photoelectron spectroscopic and electronic structure studies of CH(2)O bonding
      and reactivity on ZnO surfaces: steps in the methanol synthesis reaction.
AB  - Adsorption of CH(2)O on ZnO(0001) has been investigated using XPS, NEXAFS,
      variable-energy photoelectron spectroscopy (PES), and density functional theory
      (DFT) calculations. CH(2)O is chemisorbed on the (0001) surface at 130 K. Its C1s
      XPS peak position at 292.7 eV and NEXAFS sigma shape resonance at 302.6 eV are
      consistent with an eta(1) bound surface geometry. Geometry optimized DFT
      calculations also indicate that CH(2)O is bound to the Zn(II) site in an eta(1)
      configuration through its oxygen atom. The variable-energy PES of the eta(1)
      bound CH(2)O/ZnO(0001) complex exhibits four valence band features at 21.2, 16.4,
      13.8, and 10.7 eV below the vacuum level providing an experimental and
      theoretical description of this surface interaction. Annealing the
      ZnO(0001)/CH(2)O surface complex to 220 K decomposes the chemisorbed CH(2)O,
      producing formyl (291.5 eV), methoxide (290.2 eV), and formate (293.6 eV)
      intermediates. Thus this reaction coordinate involves the conversion of an oxygen
      bound formaldehyde to a carbon bound formyl species on ZnO(0001). Only formate is
      formed on the ZnO(100) surface. DFT is used to explore surface intermediates and
      the transition state in the methanol synthesis reaction (MSR). The bonding
      interactions of H(2), CO, CH(3)O(-), HCO(-), and trans-HCOH to the ZnO(0001)
      surface are elucidated using geometry optimization. H(2) was found to be
      heterolytically cleaved on the ZnO(0001) surface, and carbon monoxide, formyl,
      and methoxide are calculated to be eta(1) bound. These results are consistent
      with observed metal oxide surface reactivity where heterolytic bond cleavage is
      dominant. The oxygen atom in the bound formyl was found to be activated for
      attack by a proton. This results in the planar eta(1) bound trans-HCOH surface
      species. The transition state in the gas phase rearrangement of trans-HCOH to
      formaldehyde was calculated to have a barrier of 31 kcal/mol. The correlation
      diagram for this rearrangement in the gas phase indicates that configuration
      interaction at the crossing of two levels helps to lower the barrier. A
      transition state calculation was also performed for this rearrangement on the
      ZnO(0001) surface. The surface transition state geometry is significantly
      different than the gas phase. The surface geometry is no longer planar (23
      degrees dihedral angle) and is displaced parallel to the surface. Interaction
      with the Zn(II) site at the crossing of surface bound CH(2)O and trans-HCOH
      levels further lowers the barrier to rearrangement relative to gas phase by 9
      kcal/mol. The rearrangement of trans-HCOH (carbon bound) to CH(2)O (oxygen bound)
      on ZnO(0001) was calculated to be the overall barrier of the MSR reaction.

PMID- 15154798
TI  - Synthesis, structure, and bonding of Lu7Z2Te2 (Z = Ni, Pd, Ru). Linking typical
      tricapped trigonal prisms in metal-rich compounds.
AB  - The syntheses and structures of and bonding in the title compounds are described
      and compared with those for the isostructural orthorhombic Er(7)Ni(2)Te(2) (Imm2)
      and other related phases. Single-crystal data are reported for Z = Ni, Pd. The
      condensation of tricapped trigonal prisms (TTP) into sheets and the bridging of
      these by separate Lu atoms into a 3D structure are described. The interlayer
      separation, the Lu-Lu bonding achieved, and the polar Lu-Te bonding therewith are
      all affected by the size and valence energies of Te. The two Te spacers also
      exist in capped centered Lu(6)Te trigonal prisms. In terms of extended Huckel
      band analyses, the overall bonding for both Lu-Ni and Lu-Te are optimized
      energetically, but not for Lu-Lu. The average Lu-Lu overlap populations about
      each Lu appropriately increase with a decrease in the number of its Te neighbors.

PMID- 15154799
TI  - Synthesis and properties of dimetallic M1[Pz]-M2[Schiff base] complexes.
AB  - We report the synthesis and physical characterization of a series of peripherally
      functionalized porphyrazines (pz's) 1[M(1); M(2); R], where M(1) is a metal ion
      incorporated into the pz core, M(2) is a metal ion bound to a bis(5-tert-butyl
      salicylidenimine) chelate built onto two amino nitrogen attached to the pz
      periphery, and R is a solubilizing group (either n-propyl (Pr) or 3,4,5
      trimethoxyphenyl (TMP) group) attached to the remaining carbons of the pz
      periphery. The 1[M(1); M(2); R] species are prepared from precursor pz's with a
      selenodiazole ring; they are deprotected to form the diamino pz, which reacts
      with two moles of 5-tert-butyl-2-hydroxybenzaldehyde to form the Schiff base pz.
      This is metalated to form 1[M(1); M(2); R]. The crystal structures of 1[2H; Ni;
      Pr] and 1[Cu; ClMn; Pr] are presented. The EPR spectra of the M(1)-M(2) "isomers"
      prepared with Cu(II) (S = (1)/(2)) and ClMn(III) (S = 2) ions, 1[ClMn; Cu; Pr]
      and 1[Cu; ClMn; TMP], are a superposition of spectra expected for the S = (3)/(2)
      and S = (5)/(2) total-spin manifolds that result from strong Heisenberg coupling
      between the partner spins. The exchange splitting between the two manifolds, as
      determined by temperature-dependent magnetic susceptibility measurements, is
      equivalent for the two M(1)-M(2) "isomers", Delta/k(B) approximately 20-25 K,
      which suggests a sigma-pathway for exchange coupling.

PMID- 15154800
TI  - Complex formation of isocytosine tautomers with PdII and PtII.
AB  - Isocytosine (ICH) exists in solution as two major tautomers, the keto form with
      N1 carrying a proton (1a) and the keto form with N3 being protonated (1b). In
      water, 1a and 1b exist in equilibrium with almost equal amounts of both forms
      present. Reactions with a series of Pd(II) and Pt(II) am(m)ine species such as
      (dien)Pd(II), (dien)Pt(II), and trans-(NH(3))(2)Pt(II) reveal, however, a
      distinct preference of these metals for the N3 site, as determined by (1)H NMR
      spectroscopy. Individual species have been identified by the pD dependence of the
      ICH resonances. pK(a) values (calculated for H(2)O) for deprotonation of the
      individual tautomers complexes are 6.5 and 6.4 for the N3 linkage isomers of
      dienPd(II) and dienPt(II), respectively, as well as 6.2 and 6.0 for the N1
      linkage isomers. The dimetalated species [(dienM)(2)(IC-N1,N3)](3+) (M = Pd(II)
      or Pt(II)) are insensitive over a wide range of pD. The crystal structure
      analysis of [(dien)Pd(ICH-N3)](NO(3))(2) is reported. Ab initio calculations have
      been performed for tautomer compounds of composition [(NH(3))(3)Pt(ICH)](2+), cis
      and trans-[(NH(3))(2)PtCl(ICH)](+), as well as trans-[(NH(3))(2)Pt(ICH)(2)](2+).
      Without exception, N3 linkage isomers are more stable, in agreement with
      experimental findings. As to the reasons for this binding preference, an NBO
      (natural bond orbital) analysis for [(NH(3))(3)Pt(ICH-N3)](2+)strongly suggests
      that intramolecular hydrogen bonding between trans-positioned NH(3) ligands and
      the two exocyclic groups of the ICH is of prime importance. The calculations
      furthermore show a marked pyramidalization of the NH(2) group of ICH in the
      complex once the heterocyclic ligand forms a dihedral angle <90 degrees with the
      Pt coordination plane.

PMID- 15154801
TI  - Dynamic structural change of a twisted hexaporphyrin complex by highly specific
      molecular recognition.
AB  - The highly specific molecular recognition of a twisted hexaporphyrin complex,
      tris[5,5'-bis[5,10,15-tris[methoxy(ethoxy)(2)carbonylethyl]porphyrinatozinc(II)]
      2,2'-bipyridine]ruthenium(II) chloride (2), is described. Complex 2 has two
      trisporphyrin binding sites and can bind two triamines, tris(2-aminoethyl)amine
      (3) (K(1) = 3.0 x 10(8) M(-1), K(2) = 3.0 x 10(7) M(-1)), 1,1,1
      tris(aminomethyl)ethane (4) (K(1) = 2.0 x 10(7) M(-1), K(2) = 1.4 x 10(6) M(-1)),
      tris(3-aminopropyl)amine (5) (K(1) = 3.5 x 10(6) M(-1), K(2) = 6.0 x 10(6) M(
      1)), and 1,3,5-tris(aminomethyl)benzene (6) (K(1) = 2.9 x 10(6) M(-1), K(2) = 1.2
      x 10(6) M(-1)), strongly with its torsional motion. The 1:2 complex between 2 and
      the best fit triamine 3 showed the nature of the specific rigid structure in the
      UV-vis, fluorescence, and (1)H NMR spectra and isothermal titration calorimetry
      (ITC) measurements.

PMID- 15154802
TI  - The first (ferrocenylmethyl)imidazolium and (ferrocenylmethyl)triazolium room
      temperature ionic liquids.
AB  - N-(Ferrocenylmethyl)imidazole (3a), 1-(ferrocenylmethyl)-1,2,4-triazole (3b),
      1,1'-bis[(1H-imidazol-1-yl)methyl]ferrocene (8a), 1,1'-bis([1H-(2-methyl)imidazol
      1-yl]methyl]ferrocene (8b), and 1,1'-bis[(1H-1,2,4-triazol-1-yl)methyl]ferrocene
      (8c) were synthesized in moderate yields. These compounds were quaternized with
      methyl iodide to form 1-(ferrocenylmethyl)-3-methylimidazolium iodide (4a), 1
      (ferrocenylmethyl)-4-methyl-1,2,4-triazolium iodide (4b), 1,1'-bis([1-(2,3
      dimethyl)imidazolium]methyl)ferrocene diiodide (9b), and 1,1'-bis([1-(4-methyl)
      1,2,4-triazolium]methyl)ferrocene diiodide (9c), respectively, in excellent
      yields. Compounds 4a, 4b, 9b, and 9c were metathesized with
      bis(trifluoromethanesulfonyl)amide to give high yields of 5a, 5b, 10b, and 10c.
      With potassium hexafluorophosphate, 9b forms 10d. Salts 5a, 5b, and 10c are the
      first room-temperature ionic liquids with cations containing an organometallic
      moiety that exhibit T(g) values well below room temperature, i.e., -32, -16, and 
      11 degrees C. The compounds were characterized by (1)H, (19)F, and (13)C NMR, MS,
      and elemental analyses. T(g) values and melting points were determined by DSC.
      T(d) values (5% weight loss temperature) were recorded by TGA. X-ray single
      crystal structures show that 9c and 10d crystallize in the triclinic space group
      P.

PMID- 15154803
TI  - Honeycomb nets with interpenetrating frameworks involving iminodiacetato
      copper(II) blocks and bipyridine spacers: syntheses, characterization, and
      magnetic studies.
AB  - Three coordination polymers of copper(II), viz. ([Cu(ida)(4,4'-bipyH)]ClO(4))(
      proportional, variant ) (1), ([Cu(2)(ida)(2)(micro-4,4'-bipy)].2H(2)O)(
      proportional, variant ) (2), and [Cu(2)(ida)(2)(bpa)]( proportional, variant )
      (3) have been synthesized by the process of self-assembly using Cu(ida) [ida =
      iminodiacetate(2-)] as the building block and 4,4'-bipyridyl and 1,2-bis(4
      pyridyl)ethane (bpa) as linkers. Crystals of 1 are orthorhombic, of space group
      Pna2(1), with a = 13.8956(12) A, b = 16.3362(16) A, c = 7.3340(12), and Z = 4.
      Both compounds 2 and 3 crystallize in monoclinic space group P2(1)/a with a =
      10.1887(8) A (9.6779(10) A for 3), b = 8.0008(11) A (9.1718(10) A), c =
      11.6684(9) A (12.9144(12) A), beta = 98.307(11) degrees (102.796(18) degrees ),
      and Z = 2 (2). Compound 1 has a zigzag chain structure with an extensive hydrogen
      bonded network while compounds 2 and 3 are honeycomb (6,3) nets with
      interpenetrating structures. Variable temperature (2-300 K) magnetic study
      indicates the presence of weak antiferromagnetic interactions (J = 0.82 +/- 0.01
      cm(-)(1)) in 1 and ferromagnetic in 2 (J = -0.45 +/- 0.05 cm(-)(1)) and 3 (J = 
      0.21 +/- 0.02 cm(-)(1)). The extent of planarity of the bridging "Cu-O-C-O-Cu"
      moiety, acting as the super-exchange pathway between the neighboring copper
      centers, probably controls the sign of the magnetic exchange coupling in these
      compounds.

PMID- 15154804
TI  - The course of (R2R'SiO)3TaCl2 (R = tBu, R' = H, Me, Ph, tBu (silox); R = iPr, R'
      = tBu, iPr) reduction is dependent on siloxide size.
AB  - Various sized siloxides (Cy(3)SiO > (t)Bu(3)SiO > (t)Bu(2)PhSiO > (t)Bu(2)MeSiO
      approximately (i)Pr(2)(t)BuSiO > (i)Pr(3)SiO > (t)Bu(2)HSiO) were used to make
      (R(2)R'SiO)(3)TaCl(2) (R = (t)Bu, R' = H (1-H), Me (1-Me), Ph (1-Ph), (t)Bu (1);
      R = (i)Pr, R' = (t)Bu (1-(i)Pr(2)); R = R' = (i)Pr (1-(i)Pr(3)); R = R' = (c)Hex
      (Cy)). Product analyses of sodium amalgam reductions of several dichlorides
      suggest that [(R(2)R'SiO)(3)Ta](2)(mu-Cl)(2) may be a common intermediate. When
      the siloxide is large (1-(t)Bu), formation of the Ta(III) species
      ((t)Bu(3)SiO)(3)Ta (6) occurs via disproportionation. When the siloxide is small,
      the Ta(IV) intermediate is stable (e.g., [((i)Pr(3)SiO)(3)Ta](2)(mu-Cl)(2) (2)),
      and when intermediate sized siloxides are used, solvent bond activation via
      unstable Ta(III) tris-siloxides is proposed to occur. Under hydrogen, reductions
      of 1-Me and 1-Ph provide Ta(IV) and Ta(V) hydrides
      [((t)Bu(2)MeSiO)(3)Ta](2)(micro-H)(2) (4-Me) and ((t)Bu(2)PhSiO)(3)TaH(2) (7-Ph),
      respectively.

PMID- 15154805
TI  - Synthesis, characterization, and solution behavior of optically active cis beta
      organocobalt salen complexes with L-amino acids.
AB  - The reaction of a cis beta folded organocobalt derivative with a salen-type
      ligand, 1, isolated as racemic compound of Delta and Lambda enantiomers, with
      enantiomerically pure alpha-l amino acids is reported. The reaction between
      racemic 1 and l-tyrosine afforded a mixture of the two diastereoisomers Delta-2
      and Lambda-2, which could be separated by fractional crystallization owing to the
      lower solubility of Delta-2. The absolute configuration of the two diastereomers
      was unequivocally assigned from the X-ray structure, using the known absolute
      configuration of the asymmetric carbon of the amino acid as internal reference.
      The reaction of racemic 1 with trans-4-hydroxy-l-proline afforded only the
      diastereoisomer with a Delta configuration of the tetradentate ligand, as proved
      by X-ray diffractometric analysis. For both l-tyrosine and trans-4-hydroxy-l
      proline, the amino acid initially coordinates both to the Delta and to the Lambda
      enantiomers of 1, leading to an about equimolar mixture of diastereoisomers. In
      the case of l-tyrosine the diastereoisomers have about the same energy, so that
      the successive isomerization is negligible. In the case of trans-4-hydroxy-l
      proline, Delta-3 is much more stable than Lambda-3, and the isomerization
      reaction Lambda-3 --> Delta-3 goes practically to completion.

PMID- 15154806
TI  - Photocatalytic synthesis of copper colloids from CuII by the ferrihydrite core of
      ferritin.
AB  - The iron-storage protein ferritin encapsulates a nanoparticle of iron oxide. The
      size and properties of these nanoparticles can be adjusted by controlled
      oxidative hydrolysis reactions of Fe(II). This mineralized ferritin protein cage
      has previously been shown to act as an effective photocatalyst for reduction of
      Cr(VI). In the present work, we demonstrate that Fe(O)OH-mineralized ferritin
      catalyzes the photoreduction of Cu(II) to form a stable, air-sensitive, colloidal
      dispersion of Cu(0). In addition, the particle sizes of the Cu colloids can be
      controlled by varying the ratio of Cu(II) to ferritin. This illustrates an
      important principle, namely that the properties of one preformed material can be
      utilized for the specific synthesis of a second material, thus tailoring the
      desired physical properties of the final products. This procedure represents a
      multistep materials synthesis: the formation of a new nanomaterial from a
      catalytic precursor.

PMID- 15154807
TI  - Ionic liquids based upon metal halide/substituted quaternary ammonium salt
      mixtures.
AB  - The synthesis of ionic liquids based upon functionalized quaternary ammonium
      salts and metal salts of zinc, tin, or iron is demonstrated. The freezing point
      of these ionic liquids was studied as a function of the quaternary ammonium
      cation. The complex anions were identified and quantified using mass spectrometry
      and potentiometry. It is shown that the primary zinc anion is Zn(2)Cl(5)(-) with
      Zn(3)Cl(7)(-) becoming more abundant in more Lewis basic solutions. Similar
      results were observed for ionic liquids containing SnCl(2). The surface tension
      was also measured and was used to explain the high viscosity of the ionic liquids
      in terms of the large ion:hole size ratio and the small probability of finding a
      hole of suitable dimensions adjacent to a given ion to permit movement. The phase
      behavior of a variety of quaternary ammonium halides/ZnCl(2) mixtures is
      characterized and it is shown that the depression of freezing point is related to
      the increase in size of the component ions.

PMID- 15154808
TI  - Lithiation of (tBuNH)3PNSiMe3 and formation of tetraimidophosphate complexes
      containing M3O3 rings (M = Li, K): X-ray structure of the stable radical
      [(Me3SiN)P(mu3-N(t)Bu)3[mu3-Li(THF)]3(OtBu)).
AB  - The reaction of ((t)BuNH)(3)PNSiMe(3) (1) with 1 equiv of (n)BuLi results in the
      formation of Li[P(NH(t)Bu)(2)(N(t)Bu)(NSiMe(3))] (2); treatment of 2 with a
      second equivalent of (n)BuLi produces the dilithium salt
      Li(2)[P(NH(t)Bu)(N(t)Bu)(2)(NSiMe(3))] (3). Similarly, the reaction of 1 and
      (n)BuLi in a 1:3 stoichiometry produces the trilithiated species
      Li(3)[P(N(t)Bu)(3)(NSiMe(3))] (4). These three complexes represent imido
      analogues of dihydrogen phosphate [H(2)PO(4)](-), hydrogen phosphate [HPO(4)](2)(
      ), and orthophosphate [PO(4)](3)(-), respectively. Reaction of 4 with alkali
      metal alkoxides MOR (M = Li, R = SiMe(3); M = K, R = (t)Bu) generates the imido
      alkoxy complexes [Li(3)[P(N(t)Bu)(3)(NSiMe(3))](MOR)(3)] (8, M = Li; 9, M = K).
      These compounds were characterized by multinuclear ((1)H, (7)Li, (13)C, and
      (31)P) NMR spectroscopy and, in the cases of 2, 8, and 9.3THF, by X-ray
      crystallography. In the solid state, 2 exists as a dimer with Li-N contacts
      serving to link the two Li[P(NH(t)Bu)(2)(N(t)Bu)(NSiMe(3))] units. The monomeric
      compounds 8 and 9.3THF consist of a rare M(3)O(3) ring coordinated to the
      (LiN)(3) unit of 4. The unexpected formation of the stable radical
      [(Me(3)SiN)P(mu(3)-N(t)Bu)(3)[mu(3)-Li(THF)](3)(O(t)Bu)] (10) is also reported. X
      ray crystallography indicated that 10 has a distorted cubic structure consisting
      of the radical dianion [P(N(t)Bu)(3)(NSiMe(3))](.2)(-), two lithium cations, and
      a molecule of LiO(t)Bu in the solid state. In dilute THF solution, the cube is
      disrupted to give the radical monoanion [(Me(3)SiN)((t)BuN)P(mu
      N(t)Bu)(2)Li(THF)(2)](.-), which was identified by EPR spectroscopy.

PMID- 15154809
TI  - Rational syntheses, structure, and properties of the first bismuth(II)
      carboxylate.
AB  - Bismuth(II) trifluoroacetate (1), the first inorganic salt of bismuth in
      oxidation state +2, has been obtained in its pure, unstabilized form. Several
      synthetic routes suggested for the isolation of the new compound include (i) mild
      oxidation of elemental bismuth with some metal trifluoroacetates, e.g., Ag(I) and
      Hg(II); (ii) mild reduction of bismuth(III) trifluoroacetate with metals, such as
      Zn; (iii) comproportionation reaction between Bi and Bi(O(2)CCF(3))(3). The last
      approach gives the title compound 1 in quantitative yield as a sole product.
      Bismuth(II) trifluoroacetate has been characterized by NMR, IR, and UV-vis
      spectroscopy as well as by single-crystal X-ray diffraction. Crystallographic
      study reveals the dinuclear paddle-wheel structure for diamagnetic molecules
      Bi(2)(O(2)CCF(3))(4). The Bi-Bi bond distances in dimetal units of 1 are averaged
      to 2.9462(3) A, and there are no axial intermolecular contacts between these
      units in the solid state. The compound is volatile and exists in vapor phase up
      to 220 degrees C when it disproportionates back to Bi(0) and Bi(III) species,
      i.e., by the reverse of the synthetic route iii. In contrast, the solution
      chemistry is quite limited: the bismuth(II) trifluoroacetate is decomposed by the
      majority of common solvents, but it can be stabilized by aromatic systems. The
      dibismuth unit has been shown to be preserved in the latter solvents and can be
      crystallized out in a form of pi-adducts with arenes. Two such adducts,
      Bi(2)(O(2)CCF(3))(4).(C(6)H(5)Me) (2) and Bi(2)(O(2)CCF(3))(4).(1,4
      C(6)H(4)Me(2))(2) (3), have been isolated as single crystals and characterized by
      X-ray diffraction techniques. In the structures of both 2 and 3, the bismuth(II)
      centers exhibit weak eta(6)-coordination to aromatic rings.

PMID- 15154810
TI  - Syntheses of functionalized ferratricarbadecaboranyl complexes.
AB  - The reactions of nitriles (RCN) with arachno-4,6-C(2)B(7)H(12)(-) provide a
      general route to functionalized tricarbadecaboranyl anions, 6-R-nido-5,6,9
      C(3)B(7)H(9)(-), R = C(6)H(5) (2(-)), NC(CH(2))(4) (4(-)), (p
      BrC(6)H(4))(Me(3)SiO)CH (6(-)), C(14)H(11) (8(-)), and H(3)BNMe(2)(CH(2))(2) (10(
      )). Further reaction of these anions with (eta(5)-C(5)H(5))Fe(CO)(2)I yields the
      functionalized ferratricarbadecaboranyl complexes 1-(eta(5)-C(5)H(5))-2-C(6)H(5)
      closo-1,2,3,4-FeC(3)B(7)H(9) (3), 1-(eta(5)-C(5)H(5))-2-NC(CH(2))(4)-closo
      1,2,3,4-FeC(3)B(7)H(9) (5), 1-(eta(5)-C(5)H(5))-2-[(p-BrC(6)H(4))(Me(3)SiO)CH]
      closo-1,2,3,4-FeC(3)B(7)H(9) (7), 1-(eta(5)-C(5)H(5))-2-C(14)H(11)-closo-1,2,3,4
      FeC(3)B(7)H(9) (9), and 1-(eta(5)-C(5)H(5))-2-H(3)BNMe(2)(CH(2))(2)-closo-1,2,3,4
      FeC(3)B(7)H(9) (11). Reaction of 11 with DABCO (triethylenediamine) resulted in
      removal of the BH(3) group coordinated to the nitrogen of the side chain, giving
      1-(eta(5)-C(5)H(5))-2-NMe(2)(CH(2))(2)-closo-1,2,3,4-FeC(3)B(7)H(9) (12).
      Crystallographic studies of complexes 3, 5, 7, 9, and 11 confirmed that these
      complexes are ferrocene analogues in which a formal Fe(2+) ion is sandwiched
      between the cyclopentadienyl and tricarbadecaboranyl monoanionic ligands. The
      metals are eta(6)-coordinated to the puckered six-membered face of the
      tricarbadecaboranyl cage, with the exopolyhedral substituents bonded to the low
      coordinate carbon adjacent to the iron.

PMID- 15154811
TI  - Structure and dynamics of a dihydrogen/hydride ansa molybdenocene complex.
AB  - In contrast to [Cp(2)MoH(3)](+), which is a thermally stable trihydride complex,
      the ansa-bridged analogue [(eta-C(5)H(4))(2)CMe(2)MoH(H(2))](+) (1) is a
      thermally labile dihydrogen/hydride complex. Partial deuteration of the hydride
      ligands allows observation of J(H)(-)(D) = 11.9 Hz in 1-d(1) and 9.9 Hz in 1-d(2)
      (245 K), indicative of a dihydrogen/hydride structure. There is a slight
      preference for deuterium to concentrate in the dihydrogen ligand. A rapid dynamic
      process interchanges the hydride and dihydrogen moieties in complex 1. Low
      temperature (1)H NMR spectra of 1 give a single hydride resonance, which broadens
      at very low temperature due to rapid dipole-dipole relaxation (T(1) = 23 ms (750
      MHz, 175 K) for the hydride resonance in 1). Low temperature (1)H NMR spectra of
      1-d(2) allow the observation of decoalescence at 180 K into two resonances. The
      bound dihydrogen ligand exhibits hindered rotation with DeltaG(150) = 7.4
      kcal/mol, but H atom exchange is still rapid at all accessible temperatures (down
      to 130 K). Density functional calculations confirm the dihydrogen/hydride
      structure as the ground state for the molecule and give estimates for the energy
      of two hydrogen exchange processes in good agreement with experiment. The
      presence of the C ansa bridge is shown to decrease the ability of the metallocene
      fragment to donate to the hydrogens, thus stabilizing the (eta(2)-H(2)) unit and
      modulating the barrier to H(2) rotation.

PMID- 15154812
TI  - Luminescent Ag i-Cu i heterometallic hexa-, octa-, and hexadecanuclear alkynyl
      complexes.
AB  - A series of Ag(I)-Cu(I) heteronuclear alkynyl complexes were prepared by reaction
      of polymeric (MCCC(6)H(4)R-4)(n)() (M = Cu(I) or Ag(I); R = H, CH(3), OCH(3),
      NO(2), COCH(3)) with [M'(2)(mu-Ph(2)PXPPh(2))(2)(MeCN)(2)](ClO(4))(2) (M' = Ag(I)
      or Cu(I); X = NH or CH(2)). Heterohexanuclear complexes [Ag(4)Cu(2)(mu
      Ph(2)PNHPPh(2))(4)(CCC(6)H(4)R-4)(4)](ClO(4))(2) (R = H, 1; CH(3), 2) were
      afforded when X = NH, and heterooctanuclear complexes [Ag(6)Cu(2)(micro
      Ph(2)PCH(2)PPh(2))(3)(CCC(6)H(4)R-4)(6)(MeCN)](ClO(4))(2) (R = H, 3; CH(3), 4;
      OCH(3), 5; NO(2), 6) were isolated when X = CH(2). Self-assembly reaction between
      (MCCC(6)H(4)COCH(3)-4)(n) and [M'(2)(mu
      Ph(2)PCH(2)PPh(2))(2)(MeCN)(2)](ClO(4))(2), however, gave heterohexadecanuclear
      complex [Ag(6)Cu(2)(micro-Ph(2)PCH(2)PPh(2))(3)(CCC(6)H(4)COCH(3)
      4)(6)](2)(ClO(4))(4) (7). The heterohexanuclear complexes 1 and 2 show a bicapped
      cubic skeleton (Ag(4)Cu(2)C(4)) consisting of four Ag(I) and two Cu(I) atoms and
      four acetylide C donors. The heterooctanuclear complexes 3-6 exhibit a waterwheel
      like structure that can be regarded as two Ag(3)Cu(CCC(6)H(5))(3) components put
      together by three bridging Ph(2)PCH(2)PPh(2) ligands. The heterohexadecanuclear
      complex 7 can be viewed as a dimer of heterooctanuclear complex [Ag(6)Cu(2)(micro
      Ph(2)PCH(2)PPh(2))(3)(CCC(6)H(4)COCH(3)-4)(6)](ClO(4))(2) through the silver and
      acetyl oxygen (Ag-O = 2.534 (4) A) linkage between two waterwheel-like Ag(6)Cu(2)
      units. All of the complexes show intense luminescence in the solid states and in
      fluid solutions. The microsecond scale of lifetimes in the solid state at 298 K
      reveals that the emission is phosphorescent in nature. The emissive state in
      compounds 1-5 is likely derived from a (3)LMCT (CCC(6)H(4)R-4 --> Ag(4)Cu(2) or
      Ag(6)Cu(2)) transition, mixed with a metal cluster-centered (d --> s) excited
      state. The lowest lying excited state in compounds 6 and 7 containing electron
      deficient 4-nitrophenylacetylide and 4-acetylphenylacetylide, respectively,
      however, is likely dominated by an intraligand (3)[pi --> pi] character.

PMID- 15154813
TI  - Diimine-acetylide compounds of ruthenium: the structural and spectroscopic
      effects of oxidation.
AB  - The reaction of Ru(Me(2)bipy)(PPh(3))(2)Cl(2) 1 with terminal alkynes HCCR in the
      presence of TlPF(6) leads to the formation of the vinylidene compounds
      [Ru(Me(2)bipy)(PPh(3))(2)Cl(=C=CHR)][PF(6)] (2) (2a, R = Bu(t); 2b, R = p
      C(6)H(4)-Me; 2c, R = Ph). These compounds decompose in oxygenated solution to
      form the carbonyl compound [Ru(Me(2)bipy)(PPh(3))(2)Cl(CO)][PF(6)] (3), and may
      be deprotonated by K(2)CO(3) to give the ruthenium(II) terminal acetylide
      compounds Ru(Me(2)bipy)(PPh(3))(2)Cl(CC-R) (4) (4a, R = Bu(t); 4b, R = p-C(6)H(4)
      Me; 4c, R = Ph). Cyclic voltammetry shows that 2a-c may also be reductively
      dehydrogenated to form 4a-c. 4a-c are readily oxidized to their ruthenium(III)
      analogues [4a](+)-[4c](+), and the changes seen in their UV/visible spectra upon
      performing this oxidation are analyzed. These show that whereas the UV/visible
      spectra of 4a-c show MLCT bands from the ruthenium atom to the bipyridyl ligand,
      those of [4a](+)-[4c](+) contain LMCT bands originating on the acetylide ligands.
      This is in agreement with the IR and ESR spectra of [4a](+)-[4c](+). The X-ray
      crystal structures of the redox pair 4a and [4a][PF(6)()] have been determined,
      allowing the bonding within the metal-acetylide unit to be analyzed, and an
      attempt is made to determine Lever electrochemical parameters (E(L)) for the
      vinylidene and acetylide ligands seen herein. Room temperature luminescence
      measurements on 4a-c show that the compounds are not strongly emissive.

PMID- 15154814
TI  - Light-induced metastable states in oxalatenitrosylruthenium(II) and
      terpyridinenitrosylruthenium(II) complexes.
AB  - Two extremely long lived metastable states (SI and SII) can be accessed by
      irradiation with light in the blue-green spectral range at temperatures below 200
      K in Cs(2)[Ru(ox)(NO)Cl(3)], [Ni(cyclam)][Ru(ox)(NO)Cl(3)].3H(2)O, and
      [Ru(terpy)(NO)(OH)Cl][PF(6)]. The crystal structures of the ground states of the
      oxalate-containing compounds are presented, and the influence of the atomic
      distances of the cations/anions is discussed with respect to the decay
      temperatures. The radiationless thermal decay of the metastable states is
      detected by differential scanning calorimetry (DSC) for the three compounds. Both
      metastable states decay exponentially in time under isothermal conditions. The
      excited states are energetically separated from the ground state by potential
      barriers given by the activation energy of the Arrhenius law. In
      [Ni(cyclam)][Ru(ox)(NO)Cl(3)].3H(2)O the enthalpy maximum of the thermal decay of
      SII appears at 182 K, which is a relatively high decay temperature for SII. The
      reason for this strong temperature shift compared to those of the other compounds
      could be due to the polarization effect of Ni(2+) on the electron density at the
      Ru site via the Cl atom.

PMID- 15154815
TI  - Sterically hindered and robust pnictogen ligands derived from carboranes:
      synthesis and X-ray structure determination of tris(1'-methyl(1,2-dicarba-closo
      dodecaboran-1-yl))phosphine, tris(1'-methyl(1,2-dicarba-closo-dodecaboran-1
      yl))arsine and chloro(tris(1'-methyl(1,2-dicarba-closo-dodecaboran-1
      yl))phosphine)gold(I).
AB  - Sterically hindered phosphine and arsine ligands derived from ortho-carborane
      were synthesized and characterized by X-ray crystallography. Tris(1'-methyl(1,2
      dicarba-closo-dodecaboran-1-yl))phosphine, 2 (crystal data, hexagonal, space
      group P6(3), a = b = 12.251(3) A, c = 11.514(4) A, alpha = beta = 90 degrees,
      gamma = 120 degrees, V = 1496.6(7) A(3), Z = 2, R(1) = 0.0568) and tris(1'
      methyl(1,2-dicarba-closo-dodecaboran-1-yl))arsine, 3 (crystal data, hexagonal,
      space group P6(3), a = b = 12.330(3) A, c = 11.474(4) A, alpha = beta = 90
      degrees, gamma = 120 degrees, V = 1510.7(7) A(3), Z = 2, R(1) = 0.0930) were
      prepared in 82% and 68% yield, respectively. The phosphine ligand is resistant to
      air-oxidation but was converted to corresponding oxide when heated with hydrogen
      peroxide. The tertiary carboranyl phosphine reacted with (Tht)AuCl to yield
      chloro(tris(1'-methyl(1,2-dicarba-closo-dodecaboran-1-yl))phosphine)gold(I), 4
      (crystal data, monoclinic, space group P2(1)/c, a = 19.101(4) A, b = 12.167(2) A,
      c = 13.846(3) A, alpha = gamma = 90 degrees, beta = 91.13(3) degrees, V =
      3217.2(11) A(3), Z = 4, R(1) = 0.0396) in 82% yield. From the X-ray structure of
      the gold complex, the cone angle of the phosphine was determined to be 213(2)
      degrees, which is among the largest values reported to date.

PMID- 15154816
TI  - Functionalization of polyoxometalates: from Lindqvist to Keggin derivatives. 1.
      synthesis, solution studies, and spectroscopic and ESI mass spectrometry
      characterization of the rhenium phenylimido tungstophosphate [PW11O39(ReNC6H5)]4
      .
AB  - Reaction of [Bu(4)N](4)[H(3)PW(11)O(39)] with [Re(NPh)Cl(3)(PPh(3))(2)], in
      acetonitrile and in the presence of NEt(3), provided the first Keggin-type
      organoimido derivative [Bu(4)N](4)[PW(11)O(39)(ReNPh)] (Ph = C(6)H(5)) (1). The
      functionalization was clearly demonstrated by various techniques including (1)H
      and (14)N NMR, electrochemistry, and ESI mass spectrometry. Conditions for the
      formation of 1 are also discussed.

PMID- 15154817
TI  - (trans-1,4-bis[(4-pyridyl)ethenyl]benzene)(2,2'-bipyridine)ruthenium(II)
      complexes and their supramolecular assemblies with beta-cyclodextrin.
AB  - Two novel ruthenium polypyridine complexes, [Ru(bpy)(2)Cl(BPEB)](PF(6)) and
      ([Ru(bpy)(2)Cl](2)(BPEB))(PF(6))(2) (BPEB = trans-1,4-bis[2-(4
      pyridyl)ethenyl]benzene), were synthesized and their characterization carried out
      by means of elemental analysis, UV-visible spectroscopy, positive ion
      electrospray (ESI-MS), and tandem mass (ESI-MS/MS) spectrometry, as well as by
      NMR spectroscopy and cyclic voltammetry. Cyclic and differential pulse
      voltammetry for the mononuclear complex showed three set of waves around 1.2 V
      (Ru(2+/3+)), -1.0 V (BPEB(0/)(-)), and -1.15 (BPEB(-/2-)). This complex exhibited
      aggregation phenomena in aqueous solution, involving pi-pi stacking of the
      planar, hydrophobic BPEB ligands. According to NMR measurements and variable
      temperature experiments, the addition of beta-cyclodextrin (betaCD) to
      [Ru(bpy)(2)Cl(BPEB)](+) leads to an inclusion complex, breaking down the
      aggregated array.

PMID- 15154818
TI  - Hydrothermal syntheses, crystal structures, and characteristics of a series of Cd
      btx coordination polymers (btx = 1,4-Bis(triazol-1-ylmethyl)benzene).
AB  - Four novel cadmium-btx (btx = 1,4-bis(triazol-1-ylmethyl)benzene) coordination
      polymers [Cd(btx)(2)(NO(3))(2)](n)(1), [Cd(btx)(2)Cl(2)](n)(2),
      [Cd(btx)(SO(4))(H(2)O)(2)](n)(3), and [Cd(btx)(S(2)O(7))(H(2)O)](n)(4) have been
      prepared by hydrothermal reaction (140 or 180 degrees C) and characterized. Both
      1 and 2 have two-dimensional rhombohedral grid structures, 3 possesses a two
      dimensional rectangular grid structure, and 4 displays a three-dimensional
      framework, which is formed by btx bridging parallel layers. To the author's best
      knowledge, polymer 4 is the first Cd(II) polymer in which the Cd(II) ion is eight
      coordinated in a hexagonal bipyrimidal geometry. In addition, we studied the
      effects of temperature on the hydrothermal reaction system of btx and CdSO(4) and
      found that different products can be obtained at different temperatures.
      Furthermore, polymer 3 possesses a very strong third-order NLO absorptive effect
      with an alpha(2) value of 1.15 x 10(-)(9) m W(-1). Polymers 2-4 display strong
      fluorescent emissions in the solid state at room temperature. The DTA and TGA
      results of the four polymers are in agreement with the crystal structures.

PMID- 15154819
TI  - Molecular structure and conformations of 2,2-di-tert-butyl-1,3-diaza-2
      silacyclopentane: gas electron diffraction and quantum chemical calculations.
AB  - The geometric structure and conformational properties of the saturated five
      membered-ring compound 2,2-di-tert-butyl-1,3-diaza-2-silacyclopentane, (t
      Bu)(2)Si(NH)(2)(CH(2))(2), was investigated by gas electron diffraction and
      quantum chemical methods (B3LYP and MP2 with 6-31G basis sets). The compound
      exists as a mixture of two conformers, both possessing a twist conformation and
      C(2) symmetry. In the prevailing form (76(6) % at 305 K) the N-H bonds stagger
      the adjacent CH(2) groups, and in the minor form the N-H bonds eclipse the CH(2)
      groups. This conformational mixture corresponds to a free energy difference of
      DeltaG degrees = 0.69(19) kcal/mol. The B3LYP method predicts a preference for
      the eclipsed conformer. The largest torsion occurs around the C-C bond with
      tau(NCCN) = 29.2(24) degrees. The degree of puckering in the title compound is
      considerably smaller than that in silacyclopentane with tau(CCCC) = 49.7(14)
      degrees. This has been rationalized by larger angle strain in the title compound.

PMID- 15154820
TI  - Structure of the hydrated and dimethyl sulfoxide solvated rubidium ions in
      solution.
AB  - The structure of the hydrated and the dimethyl sulfoxide solvated rubidium ions
      in solution has been determined by means of large-angle X-ray scattering (LAXS)
      and extended X-ray absorption fine structure (EXAFS) studies. The models of the
      hydrated and dimethyl sulfoxide solvated rubidium ions fitting the experimental
      data best are square antiprisms with Rb-O bond distances of 2.98(2) and 2.98(3)
      A, respectively. The EXAFS data show a significant asymmetry in the Rb-O bond
      distance distribution with C(3) values of 0.0076 and 0.015 A(3), respectively. No
      second hydration sphere is observed around the hydrated rubidium ion. The
      dimethyl sulfoxide solvated rubidium ion displays a Rb-O-S bond angle of ca. 130
      degrees, which is typical for a medium hard electron acceptor such as rubidium.

PMID- 15154822
TI  - Risk management from an Asian/Pacific Rim regulatory perspective.
AB  - This article reviews the state of adverse drug reaction monitoring in five
      Asian/Pacific Rim countries (Australia, Japan, Malaysia, New Zealand and
      Singapore). Each country has an active pharmacovigilance programme managed by a
      national regulatory agency. Current methods for assessing risks and current
      methods used for risk management and communication are compared with the 'tools'
      used by the US FDA. Major positive attributes of the programmes in all five
      countries include active involvement of independent expert clinical advisory
      committees in identifying and evaluating risks through the assessment of reports
      of serious and unusual reactions, and regular communications about risks from the
      national agencies to doctors and pharmacists by means of pharmacovigilance
      bulletins. Most components of the risk-management toolbox are currently used, in
      some instances without legislated support. Variations in the way risk-management
      tools are implemented within individual national health systems are illustrated.

PMID- 15154823
TI  - Risk management : a European regulatory perspective.
AB  - Risk management for European regulators means the detection and assessment of
      risks, the development and selection of measures to reduce risk, and monitoring
      of the effectiveness of risk control; all aspects of pharmacovigilance intended
      to minimise risk to European Union citizens associated with use of medicinal
      substances. This incorporates earlier and better planning of pharmacovigilance
      through formal product risk-management plans, better use of information tools to
      protect public health and routine audit of effectiveness of regulatory action.

PMID- 15154824
TI  - CIOMS and ICH initiatives in pharmacovigilance and risk management: overview and
      implications.
AB  - In this article we review the current initiatives by the Council for
      International Organizations of Medical Sciences (CIOMS) and the International
      Conference on Harmonisation (ICH) on pharmacovigilance planning that are due for
      general release during 2004. These initiatives could form the basis for applying
      concepts of risk management to medicines throughout their life cycle, from
      preclinical and clinical development to marketed use. The CIOMS VI Working Group
      (with 28 senior scientists worldwide from drug regulatory authorities and
      pharmaceutical companies) is currently developing scientific guidance that
      relates to clinical trials for medicines during development. It recommends a
      developmental pharmacovigilance concept - a 'living' concept that would start
      early in drug development supporting the science and ethics of research leading
      up to licensing (marketing authorisation) and continuing to post-authorisation
      (postmarketing) pharmacovigilance. This approach is seen as complementary to
      current ICH initiatives called 'Pharmacovigilance Planning'. ICH will introduce
      two concepts in pharmacovigilance management of medicinal products: the
      'Pharmacovigilance Specification' and the 'Pharmacovigilance Plan'. The
      'Pharmacovigilance Specification' will summarise important knowns and unknowns
      about the medicine. It will include safety risks identified at the licensing
      stage, potential risks and any key missing information. These elements will be
      essential to the formulation of pharmacovigilance plans. Dialogue and common
      understanding between regulators and the pharmaceutical industry will be a key
      factor for developing pharmacovigilance plans during the life cycle of medicines.
      Appropriate interaction with health professionals and patients should also be
      planned for the future as regulatory systems become more transparent. Where no
      significant issues are apparent at the licensing (marketing authorisation) stage,
      routine pharmacovigilance practices will be followed during the marketing phase.
      Where issues do exist or the data are limited, further study, including
      epidemiological approaches can be planned. All types of medicines (new drugs,
      biological agents, orphan drugs) may be involved in these concepts, as would
      major extensions to existing medicines. Currently ongoing CIOMS and ICH
      initiatives are in line with emerging risk-management strategies in the US, the
      European Union and Japan aimed at early and proactive pharmacovigilance.

PMID- 15154825
TI  - Communication of medical product risk: how effective is effective enough?
AB  - Ever-increasing attention is being paid worldwide to the safety of medical
      products, and the risks associated with their use. The integral role of risk
      communication in overall risk management is demonstrated by several recent market
      withdrawals of drugs, in which a perceived incapability of healthcare systems to
      manage well-characterised, avoidable risks was a significant factor. With
      advances in clinical pharmacology, pharmacogenomics and pharmacoepidemiology
      expanding our knowledge of medical products, effective delivery of the latest
      safety-related information to health professionals and consumers becomes even
      more imperative. In this regard, it is important to evaluate whether current
      modes of risk communication lead to desired changes in relevant behaviours such
      as prescribing or drug monitoring, particularly in context with which achieved
      level of effectiveness is deemed acceptable. This is crucial, as there have been
      product-specific risk communication efforts that achieved a fair degree of
      success, yet were not seen as effective enough to prevent market withdrawal of
      the medical product in question. In the service of improving public health
      through enhanced risk communication, it is essential to critically assess current
      methods, both as to results achieved (or not), and whether each method is
      applicable to the various types of risks associated with medical product use.
      Furthermore, just as combining methods may well improve overall risk
      communication, there are societal and psychological factors that must be
      considered in attempting to maximise effectiveness. However, in assessing risk
      communication effectiveness, the particular benefit- risk relationship of any
      individual medical product must also be part of the evaluative process.

PMID- 15154827
TI  - A problem-oriented approach to safety issues in drug development and beyond.
AB  - Human safety issues arise throughout the life cycle of pharmaceutical products
      and relevant information comes from a multitude of sources. Assessment and
      management of risks to humans requires a problem-based analysis to bring together
      relevant information regardless of source. The Safety Evaluation Plan (SEP) is a
      tool to support problem-oriented safety analysis. Safety issues are specified and
      the evaluation and management of each problem is based on a status summary that
      integrates the most current information from all relevant sources. The status
      summary is updated regularly during the course of clinical development to reflect
      the results of new studies and new clinical trials. In the postmarketing period,
      relevant postmarketing data is incorporated. Recent regulatory initiatives
      emphasise early identification of product safety risks so that appropriate risk
      management measures can be instituted at the time of approval. A problem-oriented
      approach supports growing regulatory expectations regarding risk assessment and
      risk management. The problem-oriented approach facilitates early identification
      of safety issues and an evidence-based approach to their evaluation. Proactive
      management of safety problems leads to prompt assessment of risks and timely and
      appropriate steps aimed at risk reduction. The SEP provides a single global
      assessment for each safety issue. Regulatory submissions for pharmaceutical and
      biological products are organised by type of information. International
      Conference of Harmonisation documents covering clinical safety issues structure
      and analyse information separately by type, for example, adverse events, serious
      adverse events, laboratory data, vital signs, etc. A problem-oriented analysis
      would need to find a place in the regulatory process. A problem-oriented approach
      to safety cuts across typical structures in the pharmaceutical industry where
      different groups handle preclinical, clinical and postmarketing safety
      information. The SEP can improve communication within the company and externally.
      Nonetheless, supporting structures need to be adapted to support such an
      interdisciplinary process. Overall, the problem-oriented approach, supported by a
      SEP, contributes to realistic expectations and sustained credibility when dealing
      with safety issues.

PMID- 15154828
TI  - The periodic safety update report as a pharmacovigilance tool.
AB  - The periodic safety update report for marketed drugs (PSUR) was designed to be a
      stand-alone document that allows a periodic but comprehensive assessment of the
      worldwide safety data of a marketed drug or biological product. The PSUR can be
      an important source for the identification of new safety signals, a means of
      determining changes in the benefit-risk profile, an effective means of risk
      communication to regulatory authorities and an indicator for the need for risk
      management initiatives, as well as a tracking mechanism monitoring the
      effectiveness of such initiatives. For these reasons, the PSUR can be an
      important pharmacovigilance tool. Numerous steps are involved in the PSUR process
      including: intake of adverse drug reaction information, case processing, data
      retrieval, data analysis, and medical review and risk assessment. These processes
      are heavily reliant on the availability of adequate resources. An overarching
      principle throughout the PSUR process is the need for a proactive approach in
      order to identify the critical steps in the process and to have a clear
      understanding of the consequences of any critical 'mis-step'. With this
      information comes appropriate planning, building quality into each step of the
      PSUR process and monitoring performance will maximise the likelihood of
      generating a quality report. Any failure of a key PSUR process will have the
      opposite effect - a poor quality report that will give little insight into
      emerging safety signals or provide misleading information that can adversely
      affect public health. A pragmatic approach that will avoid or minimise these
      pitfalls includes the following: adequate resource planning, training,
      development of 'scripts' designed to maximise the capture of key information for
      medically important reactions, standardised and harmonised Medical Dictionary for
      Regulatory Activities (MedDRA) coding procedures, pre-specified search criteria
      for data retrieval, ongoing medical review, and metrics to evaluate the
      effectiveness and efficiencies of these processes. With these quality measures in
      place, the utility of the PSUR as an effective pharmacovigilance tool is
      enhanced.

PMID- 15154826
TI  - Clinical pharmacology: special safety considerations in drug development and
      pharmacovigilance.
AB  - The dose of a drug is a major determinant of its safety, and establishing a safe
      dose of a novel drug is a prime objective during clinical development. The design
      of pre-marketing clinical trials precludes the representation of important
      subpopulations such as children, the elderly and people with co-morbidities.
      Therefore, postmarketing surveillance (PMS) activities are required to monitor
      the safety profile of drugs in real clinical practice. Furthermore, individual
      variations in pharmacogenetic profiles, the immune system, drug metabolic
      pathways and drug-drug interactions are also important factors in the occurrence
      of adverse drug reactions. Thus, the safety of a drug is a major clinical
      consideration before and after it is marketed. A multidisciplinary approach is
      required to enhance the safety profile of drugs at all stages of development,
      including PMS activities. Clinical pharmacology encompasses a range of
      disciplines and forms the backbone of drug safety consideration during clinical
      drug development. In this review we give an overview of the clinical drug
      development process and consider its limitations. We present a discussion of
      several aspects of clinical pharmacology and their application to enhancing drug
      safety. Pharmacokinetic-pharmacodynamic modelling provides a method of predicting
      a clinically safe dose; consideration of drug pharmacokinetics in special
      populations may enhance safe therapeutics in a wider spectrum of patients, while
      pharmacogenetics provides the possibility of genotype-specific therapeutics.
      Pharmacovigilance activities are also discussed. Given the complex nature and
      unpredictability of type B reactions, PMS activities are crucial in managing the
      risks drugs pose to the general population. The various aspects of clinical
      pharmacology discussed make a strong case for this field as the backbone of
      optimising and promoting safe development and use of drugs.

PMID- 15154829
TI  - Current requirements and emerging trends for labelling as a tool for
      communicating pharmacovigilance findings.
AB  - The labelling of prescription drugs is expected to ensure the safe use of
      medicines and effect changes in use if such changes are required by new safety
      information. However, withdrawal of drugs from the market and data about
      medication errors have demonstrated the limitations of labelling as a tool for
      risk management. Regulatory initiatives in many countries aim at increasing the
      usefulness and use of labelling by healthcare professionals and patients. These
      changes in regulations and guidelines, which parallel changes in the approach to
      premarketing risk assessment and pharmacovigilance, will result in a more
      relevant and extensive characterisation of a product's safety profile and better
      international labelling consistency. But despite improvements in the format of
      labelling in some countries, labelling overall continues to be bound to
      conventional layout and restricted in its ability to meet the heterogeneous needs
      of its intended audience. Technological developments such as electronic
      prescribing and the availability of electronic decision support systems can
      effectively implement compliance with labelled conditions of use and safety
      precautions in the prescription process. It will be one of the major challenges
      to make labelling easily available and suitable for use in such systems. This
      technology, bar coding of medicines, and preventive evaluation of labelling and
      packaging for clarity, readability and potential confusion can also help reduce
      medication errors.

PMID- 15154831
TI  - Crisis management strategies.
AB  - This paper discusses the different facets of crisis as experienced within the
      pharmaceutical industry but which are also prevalent throughout other industries.
      It highlights the importance of early identification and management of crises and
      issues, which in return are strongly intertwined with a fundamental positive
      internal corporate climate. A corporate philosophy should always embrace crisis
      management with the attitude of 'when' and not 'if'; therefore, a company should
      act today and not tomorrow once a crisis is on its doorstep. Preparation is of
      utmost importance and there are several items that can be addressed even before a
      crisis has arisen. Further, this paper also provides guidance on how to deal with
      the media, what to do and what not to do, and how to appoint the appropriate
      spokesperson. In this era of fast exchange of information, crisis, which
      previously may have stayed behind corporate doors, may not do so any longer.
      Image is very important and should therefore not be risked. Crisis and issue
      management should therefore be integrated in every company's philosophy and
      standard operating procedures.

PMID- 15154830
TI  - Using MedDRA: implications for risk management.
AB  - The introduction of MedDRA, the Medical Dictionary for Regulatory Activities, as
      a standardised terminology may have a major impact on the performance of risk
      management. Thus, MedDRA is likely to have an important effect on the analysis of
      clinical trial safety data. Review of the most commonly used terms in clinical
      trial tables from the labelling of ten products indicated that each adverse event
      could be represented by many MedDRA preferred terms; this might theoretically
      lead to failure to identify differences in adverse event incidence between
      treatment arms. Possible solutions are proposed. The use of MedDRA in spontaneous
      reporting systems is a regulatory requirement in some countries. Variability in
      modes of implementation and use of the terminology are discussed; these may
      impose additional limitations on any use of spontaneous data for comparative
      purposes. There are important differences in the ways that safety databases
      interface with MedDRA and uncertainty about the most appropriate way to manage
      version changes. The characteristics of MedDRA must be taken into account when
      establishing methods for signal detection and its use will affect the retrieval
      of similar cases as required for signal evaluation. The use of MedDRA in the
      periodic safety update report is discussed. The possible use of MedDRA in
      pharmacoepidemiology is highly relevant to risk management, and some issues are
      briefly outlined. With regard to communication of risk, if MedDRA is introduced
      into existing product labelling, care must be taken that the change itself does
      not cause misunderstanding; the most appropriate use of MedDRA in this regard
      remains to be determined. There is a need for careful evaluation of MedDRA in
      fulfilling its various functions in pharmacovigilance, followed by definitive
      regulatory guidance on its use.

PMID- 15154832
TI  - Managing the interface with marketing to improve delivery of pharmacovigilance
      within the pharmaceutical industry.
AB  - The pharmaceutical industry is under pressure to improve the scientific quality
      of its decisions concerning the benefit and risks of its products while ensuring
      compliance with acceptable standards of marketing. All those in a pharmaceutical
      company who currently work within pharmacovigilance should be encouraged to lead
      from the front to examine ongoing marketing activities to see how they can be
      adapted more towards pharmacovigilance and risk management. The current irony is
      that the personnel who have the greatest influence on benefit-risk decisions of a
      product are not necessarily those who acknowledge that they are performing
      pharmacovigilance. Indeed, for all concerned, whether their orientation is
      scientific and commercial, effective communication with prescribers and consumers
      usually underpins product success. Also, a substantial 'marketing' budget is
      culturally acceptable for the pharmaceutical industry so it is logical to assume
      that resource for postmarketing activity is often made available. Given these
      realities, I suggest we should strive for an integrated marketing and risk
      management plan based on the best available evidence and that being fully aware
      and in control of the safety issues for your products is the best way to
      commercialise them successfully. This approach can still be consistent with other
      corporate responsibilities such as trying to reduce the financial burden of
      product development. If this article stimulates further debate about how the
      pharmaceutical industry can more effectively organise resources and operations to
      support pharmacovigilance, risk management, and marketing, then it will have
      achieved its purpose.

PMID- 15154833
TI  - Unravelling calcium-release channel gating: clues from a 'hot' disease.
AB  - Ryanodine receptors (RyRs) are a family of intracellular channels that mediate
      Ca2+ release from the endoplasmic and sarcoplasmic reticulum. More than 50
      distinct point mutations in one member of this family, RyR1, cause malignant
      hyperthermia, a potentially lethal pharmacogenetic disorder of skeletal muscle.
      These mutations are not randomly distributed throughout the primary structure of
      RyR1, but are grouped in three discrete clusters. In this issue of the
      Biochemical Journal, Kobayashi et al. present evidence that interdomain
      interactions between two of these mutation-enriched regions play a key role in
      the gating mechanism of RyR1.

PMID- 15154834
TI  - Prions in control of cell glycosylation.
AB  - Prion proteins that are normal cellular components or involved in pathology can
      vary little or not at all in primary amino acid sequence, but their glycosylation
      is different, e.g. in scrapie versus normal forms; in mouse strain-specific
      isolates; and in BSE (bovine spongiform encephalopathy) and variant CJD
      (Creutzfeldt-Jakob disease) versus classical CJD. The results of Nielsen et al.
      published in this issue of the Biochemical Journal show that changes in
      glycosylation are not restricted to the prion. The paper comprehensively
      characterizes a decrease in the glycosylation of the insulin receptor in scrapie
      infected neuroblastoma cells, but no change in glycosylation of the insulin-like
      growth factor-1 receptor. Thus the scrapie prion can influence glycosylation, not
      only of itself, but also of other selected cell glycoproteins.

PMID- 15154835
TI  - Actions by actin: reciprocal regulation of cortactin activity by tyrosine kinases
      and F-actin.
AB  - The polymerization of actin is catalysed by the Arp (actin-related protein) 2/3
      complex, which acts downstream of a variety of receptors and signalling cascades.
      Intermediary molecules such as cortactin bind to the Arp2/3 complex and stimulate
      its activity, thus promoting actin polymerization and actin filament
      stabilization. New data in this issue of the Biochemical Journal by the Kapus
      group suggest that cortactin is reciprocally regulated by filamentous (F) actin
      and tyrosine kinases. This suggests a new paradigm for considering the cellular
      processes that regulate the dynamic organization of the actin cytoskeleton.

PMID- 15154836
TI  - Generation of a tissue-engineered tracheal equivalent.
AB  - In this Minireview we summarize efforts to generate an autologous tissue
      engineered trachea (TET) shaped as a cylinder containing a helix of cartilage to
      form the structural component of a functional tracheal replacement. Our first
      step was to demonstrate that a composite engineered tracheal equivalent composed
      of cartilaginous cylinder could be lined with nasal epithelial cells in a nude
      mouse model. We then demonstrated the feasibility of creating the cartilage and
      fibrous portion of the trachea using autologous tissue harvested from a single
      procedure in both nude-rat and sheep models. Gross morphology and tissue
      morphology of these TET series were similar to that of native trachea.
      Histological data indicated the presence of mature cartilage formation of a
      pseudostratified columnar epithelium and the presence of mature cartilage
      surrounded by connective tissue, as would be expected of native trachea.
      Regarding the biomechanical properties, the cartilage was excellent in nude
      model; however, sheep autologous TET provided less support and therefore
      collapsed easily. In addition to utilizing the angiogenic qualities of cytokines,
      we hope to exploit the growth potentials of stromal cells derived from bone
      marrow for the production of a clinically practical, bioengineered trachea.

PMID- 15154837
TI  - Tissue-engineered skin substitutes: from in vitro constructs to in vivo
      applications.
AB  - The field of skin tissue engineering is a paradigm for the various efforts
      towards the reconstruction of other tissues and organ substitutes. As skin
      replacement, this biotechnological approach has evolved from simple cultured
      autologous epidermal sheets to more complex bilayered cutaneous substitutes. The
      various types of such substitutes are herein presented with their intended use.
      However, two integrative characteristics are analysed more specifically because
      of their critical role: neovascularization and re-innervation. Furthermore, the
      in vitro use of these various skin substitutes has shed light on various
      physiological and pathological phenomena. Thus, not only the in vivo application
      of these skin substitutes as grafts, but also their in vitro value as skin
      models, are presented.

PMID- 15154838
TI  - Effects of flow on solute exchange between fluids and supported biosurfaces.
AB  - Uptake of nutrients by cultured cells on solid supports, conversion of substrates
      by surface-bound catalysts and binding of antibodies to microtitre plates are
      examples of transport processes that are strongly influenced by the flow
      conditions in the surrounding fluid. The literature on this subject is scattered
      over widely different research fields and is often found in dated, and not
      generally available, treatises. Also, the subject is inherently complicated from
      a mathematical viewpoint, because even the simplest experimental configurations
      will usually not allow analytical solutions for the diffusion-convection
      equations describing the solute mass transport in the system. Fortunately,
      however, relatively simple expressions for the rates of mass transport can often
      be obtained in physically realistic limiting cases. The present study attempts to
      give a short overview of the main experimental models used in this field and
      presents simple equations for the estimation of solute exchange rates between
      surfaces and fluids. The models considered are: (1) uptake from an unstirred
      solution; (2) reversible binding from a perfectly stirred solution; (3)
      reversible binding through an unstirred fluid layer; (4) catalytic conversion at
      the internal surface of a tube or a slit with laminar flow; (5) adsorption by a
      surface opposite a rotating stirrer; (6) adsorption from an impinging fluid jet;
      and (7) uptake by the surface of a rotating disc. In practical situations the
      property of uniform accessibility proves to be of crucial importance. Stirring by
      ultrasound, more specifically the use of acoustic streaming in nano-devices, is
      also discussed.

PMID- 15154839
TI  - Mannan-penicillin G acylase neoglycoproteins and their potential applications in
      biotechnology.
AB  - Mannan-penicillin G acylase neoglycoproteins were prepared by the conjugation of
      Saccharomyces cerevisiae mannan with enzyme penicillin G acylase using the
      reductive amination method. Eight neoglycoproteins preparations were obtained
      after gel chromatography. The preparations contained from 42 to 67% (w/w)
      saccharides and their molar masses varied from 283 to over 1000 kDa. Significant
      biospecific interaction of separated fractions with the lectin concanavalin A was
      evaluated by the precipitation and sorption method (equilibrium constants) and
      further characterized using surface plasmon resonance to determine kinetic
      association and dissociation constants. K (D) was determined over the range 10(
      7) M. High-molar-mass preparations appeared to be more suitable for preparation
      of stable and active complexes with concanavalin A for prospective use as a
      penicillin G acylase biocatalyst in enzyme reactors. The enzyme stability of such
      complexes was significantly increased compared with the original neoglycoprotein.
      Lower-molar-mass preparations were more suitable for applications such as
      biocatalysts in bioanalytical devices.

PMID- 15154840
TI  - Uniformly oriented bacterial F0F1-ATPase immobilized on a semi-permeable
      membrane: a step towards biotechnological energy transduction.
AB  - The immobilization of F(0)F(1)-ATPase in uniform orientation is reported. The
      biotinylated and histidine-tagged subunits of the bacterial F(0)F(1)-ATPase
      complex were used for immobilization of the complex on artificial semi-permeable
      membranes resulting in 88+/-7.8 and 72+/-5.2% coupling of the enzymes. The
      immobilized enzymes retained over 90% activity. The immobilized ATPase/synthase
      was used for generation of ATP from ADP and P(i) at the expense of
      electrochemical potential energy. The re-usability, ratio of amount of enzyme
      immobilized to enzymic activity conferred on the membranes, ATP synthesized by
      assembled system and suitability of ATP generated for use in coupled enzymic
      reactions were determined.

PMID- 15154841
TI  - Biotransformation of geraniol by Rhodococcus sp. strain GR3.
AB  - Microbial degradation of geraniol, a natural monoterpene alcohol, was studied
      using a Rhodococcus sp. strain GR3 isolated from soil. The bioconversion product
      was identified as geranic acid [(2 E )-3,7-dimethylocta-2,6-dienoic acid] and its
      structure was established by (1)H-NMR, Fourier-transform IR spectrometry and GC
      MS. The optimum temperature for this bioconversion was found to be 30 degrees C,
      and the reaction proceeds to a saturation with a time constant of 12.5 h. No
      appreciable degradation of product was observed using this bacterium.

PMID- 15154842
TI  - A convenient method for the identification and expression of eukaryotic genes.
AB  - The sequences of the cDNA variant lumbrokinase and the genomic DNA of beta-casein
      gene expression regulatory elements have been submitted to the GenBank(R), DDBJ,
      EMBL and GSDB Nucleotide Sequence Databases under the accession numbers AY327442C
      and AY311384 respectively. In order to identify whether the product of a
      genetically modified or newly isolated eukaryotic gene has biological activity,
      the gene of interest is usually subcloned into a mammalian expression vector and
      then expressed in an in vitro system such as in tissue culture. In the present
      study an efficient in vivo system has been developed by employing a mammary-gland
      specific vector and expressing the targeted protein in the lactating-goat mammary
      glands. In this system, the synthesized lumbrokinase cDNA variant (LK-m) and the
      tissue-type plasminogen activator (tPA) cDNA were selected as genes of interest
      and cloned downstream of the goat beta-casein regulatory sequence. The LK-m- and
      tPA-expressing plasmids were prepared to high purity and portions (100-800
      microg) injected into lactating-goat mammary-gland tissues. High-level expression
      of the LK-m and tPA was detected, by a fibrin-agarose plate assay, as fibrin
      lysis activity. A dynamic study showed that the specific expression starts
      immediately after injection, generally reaches peak in 6-9 h, persists for 20-24
      h at peak and the expression lasts for 4 days with gradual decline in the amounts
      expressed. The potential use of this system as bioreactor for the production of
      biological proteins in place of transgenic animals is implicated from this study.

PMID- 15154843
TI  - Modified-vaccinia-virus-Ankara (MVA) priming and fowlpox-virus booster elicit a
      stronger CD8+ T-cell response in mice against an HIV-1 epitope than does a
      DNA/poxvirus prime-booster approach.
AB  - A prime-boost strategy combining FWPV (fowlpox virus) and the MVA (modified
      vaccinia virus Ankara), both expressing HIV-1 multi-V3 epitope polypeptides, was
      compared with a DNA-based Semliki Forest virus replicon/poxvirus approach for the
      induction of a CD8(+) T-cell response. Priming mice with recombinant MVA and
      boosting with recombinant FWPV, and not in the reverse order, increased the
      number of specific interferon-gamma-secreting cells in relation to the homologous
      combinations. Moreover, the improvement of the CD8(+) T-cell response with this
      combination was remarkably higher than that obtained by priming with a DNA vector
      containing a Semliki Forest virus replicon expressing the multi-epitope
      polypeptide and boosting either with recombinant MVA or FWPV. These results open
      a new and attractive alternative for vaccine preparation against HIV-1 using
      different immunogens.

PMID- 15154844
TI  - Purification of goat immunoglobulin G by immobilized metal-ion affinity using
      cross-linked alginate beads.
AB  - The alginate beads obtained by cross-linking of the polymer by epichlorohydrin
      were charged with Cu(II). The copper-charged beads could be directly used as a
      immobilized-metal-affinity-chromatographic medium for purification of goat IgG.
      The best results in the packed-bed mode were obtained by using beads charged with
      95.4 micromol/ml Cu(II). We found that we could recover 97.4% IgG with an 8-fold
      purification.

PMID- 15154845
TI  - Immobilization of pigeonpea (Cajanus cajan) urease on DEAE-cellulose paper strips
      for urea estimation.
AB  - Pigeonpea ( Cajanus cajan ) urease was immobilized on 1 cmx1 cm DEAE-cellulose
      paper strips. The optimum immobilization (51% activity) was observed at 4 degrees
      C, with a protein concentration of 1.0 mg/strip. The apparent optimum pH shifted
      from 7.3 to 6.8. Immobilized urease showed an optimal stability temperature of 67
      degrees C, compared with 47 degrees C for the soluble urease. Time-dependent
      kinetics of the thermal inactivation of the immobilized urease were examined and
      found to be monophasic as compared with the soluble enzyme, which was biphasic.
      The Michaelis constant ( K (m)) for the DEAE-cellulose-immobilized urease was
      found to be 4.75 mM, 1.5 times higher than the soluble enzyme. Immobilized strips
      stored at 4 degrees C showed an increased half-life ( t (1/2)=150 days). There
      was practically no leaching of the enzyme from the immobilized strips over a
      period of 2 weeks. These strips were used for estimating the urea content of
      blood samples; the results obtained matched well with those obtained in a
      clinical laboratory through an Autoanalyzer(R) (Zydus Co., Rome, Italy). The easy
      availability of pigeonpea urease, the ease of its immobilization on DEAE
      cellulose strips and the significantly lower cost of urease described in the
      present study makes it a suitable product for future applications in diagnostics.

PMID- 15154846
TI  - Inactivation of the bovine-spongiform-encephalopathy (BSE) agent by the acid and
      alkaline processes used in the manufacture of bone gelatine.
AB  - A validation study was carried out to determine the capacity of the traditional
      acid and alkaline processes used in the manufacture of bovine bone gelatine to
      remove and/or inactivate the transmissible agent that causes BSE (bovine
      spongiform encephalopathy). Using an accurately scaled down laboratory process
      that precisely mimicked the minimum conditions of the industrial processes,
      gelatine (gelatin) was manufactured from industrial starting material that had
      been spiked with mouse brain infected with the 301V strain of mouse-passaged BSE
      agent. Clearance factors were determined by titrating the infectivity levels of
      the infected mouse brain tissue, the gelatine extracts, and the final sterilized
      gelatine solution. The infectivity level of the spiked starting material was
      10(8.4) mouse intracerebral ID(50)/kg (ID(50) is the dose at which half of the
      challenged animals were infected). Clearance factors of 10(2.6) and 10(3.7)
      ID(50) were demonstrated for the first stages of the acid and alkaline processes
      respectively during which the bones are converted to crude gelatine. It was
      further demonstrated that the complete acid and alkaline processes both reduced
      infectivity to undetectable levels, giving clearance factors of >/=10(4.8) ID(50)
      for the acid process, and >/=10(4.9) ID(50) for the alkaline process.

PMID- 15154847
TI  - Recombinant antimicrobial peptides efficiently produced using novel cloning and
      purification processes.
AB  - Endogenous antimicrobial peptides are ubiquitous components of animal and plant
      host defences. These peptides, usually cationic and amphipathic, kill target
      cells rapidly and are efficacious against antibiotic-resistant and clinically
      relevant pathogens. A practical challenge in the development of cationic peptides
      as therapeutics is to meet the production requirements for large quantities of
      highly purified drug substance at competitive costs. While chemical peptide
      synthesis can be used to manufacture cationic peptides, we have developed cost
      effective methods for recombinant production by expressing fusion proteins
      comprised of multiple copies of the peptides. The fusion proteins accumulate in
      Escherichia coli inclusion bodies and constitute over 50% of the total cellular
      proteins. Active antimicrobial peptides are released by chemical reagents and
      purified by chromatography, combining both standard and novel approaches.
      Challenges of industrial-scale manufacturing of therapeutics were considered in
      the development of this process.

PMID- 15154848
TI  - Modified alginate and chitosan for lactic acid bacteria immobilization.
AB  - Beads with enhanced-stability acid media, which were based on alginate and
      chitosan functionalized by succinylation (increasing the anionic charges able to
      retain protons) or by acylation (improving matrix hydrophobicity), were developed
      for immobilization of bacterial cells. Beads (3 mm diameter) formed by ionotropic
      gelation with CaCl(2) presented good mechanical characteristics. After 30 min
      incubation of viable free Lactobacillus rhamnosus cells in simulated gastric
      fluid (pH 1.5), we noticed that the level of viable bacteria was undetectable.
      Bacterial immobilization in native-alginate-based beads generated a viable-cell
      count of 22-26%, whereas, when entrapped in succinylated alginate and chitosan
      beads, the percentage of viable cells was of 60 and 66%, respectively. Best
      viability (87%) was found for bacteria immobilized in N -palmitoylaminoethyl
      alginate, which affords a high protective effect, probably due to long alkyl
      pendants that improve the beads' hydrophobicity, limiting hydration in the acidic
      environment.

PMID- 15154849
TI  - Development of a highly efficient system for assessing recombinant gene
      expression in plant cell suspensions via Agrobacterium tumefaciens
      transformation.
AB  - A transient gene-expression system was developed and used to characterize
      promoter strength, to verify suitability of bacterial gene modifications for
      expression in plant cells, and to express active antibody molecules. The system
      is based on suspension tobacco cells transformed by Agrobacterium in a transient
      way. Conditions such as pre-culture of tobacco cells and the co-cultivation
      period were identified as determinants to achieve high expression levels. Under
      established conditions the activity strength of CaMV (cauliflower mosaic virus)
      35 S and ToMoTV (tomato mottle taino virus) AL1 promoters were compared. A
      modified cry gene sequence from Bacillus thuringiensis was expressed and detected
      by Western-blot analysis. A monoclonal antibody against anti-(hepatitis B virus
      surface antigen) was produced in such quantities as to allow testing of
      biological activity and preliminary characterization.

PMID- 15154851
TI  - Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms.
AB  - Triptans are the treatment of choice for acute migraine. While seemingly a
      homogenous group of drugs, results from a meta-analysis reveal significant
      differences in efficacy and tolerability among oral triptans. The incidence of
      drug-related central nervous system (CNS) side-effects with some triptans is as
      high as 15% and may be associated with functional impairment and reduced
      productivity. The occurrence of adverse events associated with triptans in
      general, and CNS side-effects in particular, may lead to a delay in initiating or
      even avoidance of an otherwise effective treatment. Potential explanations for
      differences among triptans in the incidence of CNS side-effects may relate to
      pharmacological and pharmacokinetic differences, including receptor binding,
      lipophilicity, and the presence of active metabolites. Of the triptans reviewed,
      at clinically relevant doses, almotriptan 12.5 mg, naratriptan 2.5 mg and
      sumatriptan 50 mg had the lowest incidence of CNS side-effects, while eletriptan
      40 and 80 mg, rizatriptan 10 mg and zolmitriptan 2.5 and 5 mg had the highest
      incidence. The most likely explanations for the differences in CNS side-effects
      among triptans are the presence of active metabolites and high lipophilicity of
      the parent compound and active metabolites. Eletriptan, rizatriptan and
      zolmitriptan have active metabolites, while lipophilicity is lowest for
      almotriptan and sumatriptan. If CNS side-effects are a clinically relevant
      concern in the individual patient, use of a triptan with a low incidence of CNS
      side-effects may offer the potential for earlier initiation of treatment and more
      effective outcomes.

PMID- 15154850
TI  - The CBP/p300 TAZ1 domain in its native state is not a binding partner of MDM2.
AB  - The transcriptional co-activator CBP [CREB (cAMP-response-element-binding
      protein)-binding protein] and its paralogue p300 play a key role in the
      regulation of both activity and stability of the tumour suppressor p53.
      Degradation of p53 is mediated by the ubiquitin ligase MDM2 (mouse double minute
      protein) and is also reported to be regulated by CBP/p300. Direct protein-protein
      interaction between a central domain of MDM2 and the TAZ1 (transcriptional
      adaptor zinc-binding domain) [C/H1 (cysteine/histidine-rich region 1)] domain of
      p300 and subsequent formation of a ternary complex including p53 have been
      reported previously. We expressed and purified the proposed binding domains of
      HDM2 (human homologue of MDM2) and CBP, and examined their interactions using CD
      spectroscopy. The binding studies were extended by using natively purified GST
      (glutathione S-transferase)-p300 TAZ1 and GST-p53 fusion proteins, together with
      in vitro translated HDM2 fragments, under similar solution conditions to those in
      previous studies, but omitting added EDTA, which causes unfolding and aggregation
      of the zinc-binding TAZ1 domain. Comparing the binding properties of the known
      TAZ1 interaction partners HIF-1alpha (hypoxia-inducible factor 1), CITED2
      (CBP/p300-interacting transactivator with glutamic- and aspartic-rich tail) and
      STAT2 (signal transducer and activator of transcription 2) with HDM2, our data
      suggest that TAZ1 in its native state does not serve as a specific recognition
      domain of HDM2. Rather, unfolded TAZ1 and HDM2 proteins have a high tendency to
      aggregate, and non-specific protein complexes are formed under certain
      conditions.

PMID- 15154852
TI  - Assessment of anti-migraine potential of a novel alpha-adrenoceptor agonist
      S19014: effects on porcine carotid and regional haemodynamics and human coronary
      artery.
AB  - Taking into account the drawbacks associated with the use of triptans, attempts
      are being made to explore other avenues for the treatment of migraine. Recently,
      it has been shown that both alpha1- and alpha2-adrenoceptors mediate the
      constriction of porcine carotid arteriovenous anastomoses, which has effectively
      served as an experimental model predictive of anti-migraine activity. The present
      study investigated the effects of a novel alpha-adrenoceptor agonist S19014
      (spiro[(1,3-diazacyclopent-1-ene)-5 : 2'-(4',5'-dimethylindane)] fumarate) on
      carotid and systemic haemodynamics in anaesthetized pigs, and on human isolated
      coronary arteries. Increasing doses of S19014 (1-30 micro g/kg, i.v.) produced a
      dose-dependent initial short-lasting vasopressor response and a decrease of total
      carotid blood flow and conductance. The carotid blood flow and conductance
      changes were exclusively due to constriction of carotid arteriovenous anastomoses
      (capillary blood flow increased) and were accompanied by an increase in arterio
      jugular venous oxygen saturation difference. Whereas prazosin (100 micro g/kg,
      i.v.) was ineffective, rauwolscine (300 micro g/kg, i.v.) attenuated the
      responses to S19014. The compound did not much affect the distribution of cardiac
      output to peripheral organs when compared with the vehicle group. Furthermore,
      S19014 only slightly contracted the human isolated coronary artery and its
      contractions, contrary to those of sumatriptan, were not increased in blood
      vessels pre-contracted with U46619. These results suggest that (i) the systemic
      and carotid vascular effects of S19014 are mainly mediated by alpha2
      adrenoceptors, and (ii) S19014 could be effective in the treatment of migraine
      with an improved cardiovascular tolerance.

PMID- 15154853
TI  - Nitroglycerin-induced nNOS increase in rat trigeminal nucleus caudalis is
      inhibited by systemic administration of lysine acetylsalicylate but not of
      sumatriptan.
AB  - Systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor, in
      migraineurs triggers after several hours an attack of which the precise
      mechanisms are unknown. We found previously in rats that nitroglycerin (10 mg/kg
      s.c.) is able to increase significantly after 4 h the number of neuronal nitric
      oxide synthase (nNOS)-immunoreactive neurones in the cervical part of trigeminal
      nucleus caudalis. In the present experiments, we demonstrate that the 5-HT1B/D
      agonist sumatriptan (0.6 mg/kg s.c.) does not alter this phenomenon when given
      before NTG. By contrast, pretreatment with lysine acetylsalicylate (50 mg/kg
      i.m.) attenuates the NTG-induced nNOS expression in the superficial laminae of
      trigeminal nucleus caudalis. These findings suggest that effect of NTG on nNOS at
      a high dosage may involve the cycloxygenase pathway and that activation of the
      peripheral 5-HT1B/D receptors is not able to modify this effect. These data could
      help to better understand the role of NO in the pathogenesis of headaches and the
      action of antimigraine drugs.

PMID- 15154855
TI  - Attitudes and burden of disease among self-considered migraineurs--a nation-wide
      population-based survey in Sweden.
AB  - The authors have earlier reported a 1-year prevalence of 13.2 +/- 1.9% for
      migraine in Sweden. This is a subsequent extensive postal survey of the burden of
      disease and attitudes among migraineurs in a sample (n = 423, 23% men and 77%
      women, aged 18-74 years) randomly recruited from all main regions of the country,
      representative of adults in the general Swedish population with self-considered
      migraine. Results are presented only from participants who after analysis of
      symptoms were found to fulfil the International Headache Society's migraine
      criteria. In order to assess headache duration open-mindedly, the strict time
      criterion 4-72 h was deliberately disregarded as an inclusion criterion.
      Individuals who did not consider themselves to have migraine were excluded. Less
      than half of the group (45%) had received a diagnosis of migraine from a
      physician. Accordingly, a large number of individuals that would not have come to
      attention in a clinic-based study have been included. The mean attack frequency
      was 1.3 per month, and the number of attacks per year in Swedish adults is
      approximately 10 million. A minority (27%) of sufferers have a majority (68%) of
      all attacks. The mean attack duration was 19 h. A considerable number of
      individuals reported attacks < 4 h (15.8%) or > 72 h (6.4%). Less than half of
      the individuals recovered completely between the attacks. Despite this, only
      every fourth (27%) participant was currently consulting a physician (6%
      regularly; 21% occasionally). Most of the migraineurs reported absence from
      school or work, a negative influence of migraine on the most important aspects of
      life, and an interest in testing other treatments for migraine during the last
      year. Of those (n = 231) migraineurs who had consulted a physician, about 60%
      were satisfied with information given or treatment offered. This implies,
      however, that there is still room for improvement in the management of migraine
      in Sweden.

PMID- 15154854
TI  - Psychological and sleep quality differences between chronic daily headache and
      temporomandibular disorders patients.
AB  - The aim of this study was to investigate whether chronic daily headache (CDH) and
      temporomandibular disorders (TMD) patients present with different psychological
      and sleep quality characteristics. Sixty-seven patients diagnosed with CDH,
      according to classification criteria from Silberstein et al., were matched by age
      and sex with 67 patients who had a primary diagnosis of myofascial pain (MP) and
      67 patients with a primary diagnosis of TMJ intracapsular pain (IC) according to
      the Research Diagnostic Criteria for TMD. The CDH group was comprised of three
      mutually exclusive diagnostic groups: chronic migraine (n = 35); chronic tension
      type headache (n = 26); 'other CDH' (n = 6). All patients completed a battery of
      psychological and sleep quality questionnaires. All CDH subgroups showed similar
      psychological and sleep quality profiles. Pain intensity and duration were
      controlled in the multivariate analyses (Mancova) by treating them as covariates.
      The CDH and MP groups revealed higher levels of psychological distress than the
      IC group on most psychological domains. The MP group also revealed numerically
      higher levels of psychological distress in most psychological domains than the
      CDH group, although these differences were generally not significant. We did not
      find significant differences between the three groups on post traumatic stress
      symptoms either. Sleep quality was significantly worse in the MP group than in
      the CDH and IC groups. These results are discussed in the context of multimodal
      patient evaluation and treatments that are often necessary for successful
      clinical management.

PMID- 15154856
TI  - Possible mechanisms of pain perception in patients with episodic tension-type
      headache. A new experimental model of myofascial pain.
AB  - A new experimental human model of myofascial pain using intramuscular infusion of
      a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and
      prostaglandin E2 was applied to patients with episodic tension-type headache
      (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15
      healthy controls completed the randomized, balanced, double-blinded, placebo
      controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain
      quality were recorded. The combination induced a moderate and prolonged pain in
      both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P =
      0.001). Patients reported more pain than controls both after the combination (P =
      0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was
      significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas
      pain quality and hyperalgesia were similar after the combination compared with
      placebo in the two groups. Due to side-effects nine subjects did not complete the
      study. The increased pain response, but similar qualitative pain perception, in
      ETTH patients may be explained by sensitization of peripheral nociceptors even
      though central mechanisms may also be involved.

PMID- 15154857
TI  - Chronic daily headaches in children and adolescents: a study of clinical
      characteristics.
AB  - The clinical characteristics of chronic daily headache were studied in 40
      children and adolescents, as well as the associated factors responsible for
      maintenance of the continuous headache pattern. The study of the clinical
      headache characteristics, showed a female preponderance (75%), mean age of 11
      years old at the first consultation, and onset of headache symptomatology at a
      mean age of 8.5 years old. The average time interval for the evolution of
      sporadic headache into chronic daily headache was 1.4 years, and psychosocial
      stressors were present, acutely or chronically, during the period of headache
      frequency increase in 47% of the children. Headaches were classified as
      transformed migraine (65%), mixed pattern (17.5%) and chronic tension-type
      headache (17.5%). Sixty per cent of patients had mothers with migraine. Data
      regarding common analgesic use showed an average intake of 11.2 days/month.

PMID- 15154859
TI  - MTHFR T677 homozygosis influences the presence of aura in migraineurs.
AB  - It has been suggested that folate metabolism could be involved in migraine
      pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR)
      genotypic distribution in a large migraine sample. We genotyped 230 migraine
      patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204
      nonheadache controls. The incidence of TT homozygosis for migraine in general
      (12%), MO (9%) and MA (18%) did not significantly differ from that found in
      healthy controls (13%). Differences were significant when the frequency of TT
      homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was
      compared. There was a tendency for a higher frequency of the MTHFR T allele in
      the MA group (42%) as compared to MO (29%) and controls (36%). These differences
      were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI =
      1.15-2.65). These results could indicate that the MTHFR C677T polymorphism,
      causing mild hyperhomocystinaemia, might be a genetic risk factor for
      experiencing aura among migraineurs. Overall, however, there was no association
      between migraine and the C677T MTHFR polymorphism.

PMID- 15154858
TI  - Transformed migraine and medication overuse in a tertiary headache centre-
      clinical characteristics and treatment outcomes.
AB  - Studies suggest that a substantial proportion of headache sufferers presenting to
      headache clinics may overuse acute medications. In some cases, overuse may be
      responsible for the development or maintenance of a chronic daily headache (CDH)
      syndrome. The objectives of this study are to evaluate patterns of analgesic
      overuse in patients consulting a headache centre and to compare the outcomes in a
      group of patients who discontinued medication overuse to those of a group who
      continued the overuse, in patients with similar age, sex and psychological
      profile. We reviewed charts of 456 patients with transformed migraine (TM) and
      acute medication overuse defined by one of the following criteria: 1. Simple
      analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination
      analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a
      week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate
      use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically
      considered overuse > 1 tablet per day for > 5 days per week. Patients who were
      able to undergo detoxification and did not overuse medication (based on the above
      definition) after one year of follow-up were considered to have successful
      detoxification (Group 1). Patients who were not able to discontinue offending
      agents, or returned to a pattern of medication overuse within one year were
      considered to have unsuccessful detoxification (Group 2). We compared the
      following outcomes after one year of follow-up: Number of days with headache per
      month; Intensity of headache; Duration of headache; Headache score (frequency x
      intensity). The majority of patients overused more than one type of medication.
      Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight
      (10.5%) subjects took >10 tablets per day. Considering patients seen in the last
      5 years, we found the following overused substances: Butalbital containing
      combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%;
      Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory
      medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%;
      Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%)
      were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The
      comparison between groups 1 and 2 after one year of follow-up showed a decrease
      in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P <
      0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and
      14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in
      group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully
      detoxified subjects in Group 1 returned to an episodic pattern of migraine,
      compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing
      guidelines for patients with frequent headaches are urgently needed. Successful
      detoxification is necessary to ensure improvement in the headache status when
      treating patients who overuse acute medications.

PMID- 15154860
TI  - Utility of CSF pressure monitoring to identify idiopathic intracranial
      hypertension without papilledema in patients with chronic daily headache.
AB  - The aim of the present study was to report on the utility of continuous Pcsf
      monitoring in establishing the diagnosis of idiopathic intracranial hypertension
      without papilledema (IIHWOP) in chronic daily headache (CDH) patients. We report
      a series of patients (n = 10) with refractory headaches and suspected IIHWOP
      referred to us for continuous Pcsf monitoring between 1991 and 2000. Pcsf was
      measured via a lumbar catheter and analysed for mean, peak, highest pulse
      amplitude and abnormal waveforms. A 1-2 day trial of continuous controlled CSF
      drainage (10 cc/ h) followed Pcsf monitoring. Response to CSF drainage was
      defined as improvement in headache symptoms. Patients with abnormal waveforms
      underwent a ventriculoperitoneal (VPS) or lumboperitoneal (LPS) shunt insertion.
      All patients had normal resting Pcsf (8 +/- 1 mmHg) defined as ICP < 15 mmHg.
      During sleep, all patients had B-waves and 90% had plateau waves or near plateau
      waves. All patients underwent either a VPS or LPS procedure. All reported
      improvement of their headache after surgery. Demonstration of pathological Pcsf
      patterns by continuous Pcsf monitoring was essential in confirming the diagnosis
      of IIHWOP, and provided objective evidence to support the decision for shunt
      surgery. Increased Pcsf was seen mostly during sleep and was intermittent,
      suggesting that Pcsf elevation may be missed by a single spot-check LP
      measurement. The similarity between IIHWOP and CDH suggests that continuous Pcsf
      monitoring in CDH patients may have an important diagnostic role that should be
      further investigated.

PMID- 15154861
TI  - Lack of interaction between a polymorphism in the dopamine D2 receptor gene and
      the clinical features of migraine.
AB  - The purpose of this study was to evaluate whether a particular genotype of the
      dopamine D2 receptor (DRD2) gene would affect the clinical features of migraine.
      In a group of 118 migraineurs (55 migraine with aura and 63 migraine without aura
      patients), we tested the association of the biallelic C/T NcoI DRD2 polymorphism
      with several characteristics of the disease. Genotype and allele frequencies
      resulted similarly distributed in migraine with aura and migraine without aura
      patients (chi2 = 1.58, P = 0.45 and chi2 = 0.09, P = 0.77, respectively). The
      different DRD2 genotypes (C/C, C/T and T/T) had no significant effects on age at
      onset of migraine, presence of premonitory phenomena, frequency of headache
      attacks, associated symptoms, psychological features and quality of life of our
      migraine patients. The results of our study do not support a role for the DRD2
      gene in modifying the clinical features of migraine.

PMID- 15154862
TI  - SUNCT syndrome in the elderly.

PMID- 15154863
TI  - Buspirone challenge is not a valid probe of central 5-HT1A receptor function.

PMID- 15154866
TI  - The role of apheresis therapy in living donor liver transplantation.
AB  - Liver transplantation is a radical therapy for end-stage liver disease. The
      severe shortage of transplantable organs is, however, a big problem, not only in
      liver transplantation but also other organ transplants. Although in Japan,
      transplantation of organs obtained from brain-dead donors (BDD) has been allowed
      since October 1997, to date only 27 BDD have been obtained. It has become
      difficult to procure liver grafts from BDD, therefore we must use liver grafts
      from living donors. The living-donor liver transplantation (LDLT) program started
      in 1990 in Japan, and is still the major form of liver transplantation because of
      the scarcity of cadaveric donors. In the Department of Transplant Surgery, Kyoto
      Hospital (Kyoto, Japan), the accumulated number of LDLT cases exceeded 955 up to
      October 2003. In order to perform LDLT under safer conditions, apheresis plays a
      major role in Japan due to the prevalence of LDLT where later retransplantation
      is difficult. Clinical indications of apheresis for LDLT are mainly use as a
      bridge before transplantation, and liver support after transplantation. We
      describe the effect of apheresis therapy for LDLT patients with nephritic and
      hepatic problems.

PMID- 15154867
TI  - Study of plasma exchange for liver failure: beneficial and harmful effects.
AB  - Plasma exchange (PE) is often performed in combination with hemodialysis (HD) or
      hemodiafiltration. However, most methods were developed for the treatment of
      renal failure, so various problems may arise during treatment of liver failure
      (LF). In this study, we investigated the impact of PE alone and in combination
      with HD, and we assessed the complications of using PE + HD for the treatment of
      LF. After the exchange of 1 L of fresh frozen plasma (FFP), we measured serum
      electrolytes, HCO(3) (-), citrate, and acetate at 3 points in the circuit: A) the
      plasma separator inflow; B) after mixing of FFP/the dialyzer inflow; and C) the
      dialyzer outflow. Serum levels of human hepatocyte growth factor (HGF), acetate,
      and citrate were also measured before and after PE + HD. The levels of K(+),
      Ca(++), HCO(3) (-), and acetate were significantly decreased, and citrate was
      increased, between A and B. K(+) and citrate were decreased, while Ca(++), HCO(3)
      (-), and acetate showed an increase between B and C. Comparison of A with C
      revealed insufficient correction of the Ca(++) and citrate levels by HD. After PE
      + HD, serum levels of acetate and citrate were increased, while HGF was
      decreased. We concluded that i) when PE is performed, HD is also necessary for
      correction, but achieves insufficient correction of Ca(++) and citrate, ii) PE is
      non-selective and not only removes toxins but also beneficial substances such as
      HGF, iii) accumulation of acetate occurred, even with bicarbonate dialysate,
      since it also contains acetate for acidification.

PMID- 15154868
TI  - Treatment of multiple organ failure through sepsis by surgery and blood
      purification.
AB  - For the treatment of multiple organ failure (MOF) through sepsis, we have
      commonly applied various blood purification modalities during the perioperative
      period. From January 1996 to December 2000, 33 patients with MOF through sepsis
      were admitted and operated on in the First Department of Surgery, Akita
      University School of Medicine, and 21 of these 33 patients were treated using
      various blood purification modalities during the perioperative period: endotoxin
      adsorbing therapy using polymyxin B (PMX) in 17 patients, continuous
      hemofiltration (CHF)/continuous hemodiafiltration (CHDF) in 15 patients, and
      plasma exchange (PE) and CHDF in 3 patients. Of the outcome of these 33 patients
      with MOF through sepsis, 17 survived and 16 died (48% mortality). Of the 21
      patients with MOF through sepsis treated by surgery and blood purification, 12
      survived and 9 died (43% mortality). We evaluated APACHE II and the number of
      failed organs before operation. Amongst the group with 12 survivors and 9 deaths,
      Acute Physiology and Chronic Health Evaluation II (APACHE II) was 15 +/- 5, 23 +/
      2 and the number of failed organs was 2.7 +/- 0.7, 3.9 +/- 0.8, respectively. An
      increased APACHE II score and number of failed organs were significantly
      associated with mortality. As to the treatment of MOF through sepsis due to acute
      peritonitis, patients with APACHE II scores ranging from 15 to 20, and those with
      2-3 failed organs seem to be the candidates for the application of blood
      purification during the perioperative period.

PMID- 15154869
TI  - Analysis for the optimal blood draw speed to collect sufficient peripheral blood
      mononuclear cells by COBE Spectra.
AB  - In recent years the procedures for peripheral blood mononuclear cell (PBMNC)
      harvests have gradually been increasing. These PBMNCs are collected for several
      treatments, for example, donor lymphocyte infusion (DLI), immunotherapy for solid
      carcinoma, and regeneration therapy for ischemic limbs. In order to analyze the
      optimal procedure for collecting PBMNCs safely and efficiently, we evaluated 129
      PBMNC apheresis procedures from April 1996 to May 2003, without hemopoietic stem
      cell mobilization by G-CSF. In every case, PBMNC collections were performed with
      a COBE Spectra cell separator (Gambro BCT). The median apheresis volume was 5550
      mL. The median of blood draw speed was 48.1 mL/min. The median TNC (total nuclear
      cell) number in products was 50.4 x 10(3)/ micro L. In the regression analysis,
      no significant correlation was seen between the blood draw speed and the
      concentrations of TNC in products (Y = aX + b, a = 0.842497, b = 17.11352, r =
      0.222032, P = 0.012464). A positive correlation was seen between WBC on apheresis
      day and the concentrations of TNC (Y = aX + b, a = 0.009822, b = 3.224679, r =
      0.550431, P = 2.93 x 10(-11)). A significantly higher correlation was seen
      between the MNC (mononuclear cells) on apheresis day and the concentrations of
      TNC (Y = aX + b, a = 0.028278, b = 13.09266, r = 0.696988, P = 9.486 x 10(-9)).
      This study has shown evidence that a higher increment of blood draw speed does
      not provide a higher concentration of products. An adequate apheresis speed is
      about 40 mL/min. If we want to obtain sufficient cell counts, it is very
      important to obtain sufficient volume with a moderate blood draw speed, therefore
      protecting against side-effects.

PMID- 15154870
TI  - Selective adsorption of human CD4 T cells.
AB  - The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T
      cells. To remove CD4(+) T cells selectively from the circulation, we designed a
      new column in which an anti-CD4 monoclonal antibody was immobilized on the
      activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from
      whole blood with a single passage through the column in vitro, resulting in
      depletion of the antigen-specific T cell responses. We conclude that this new
      column would be potentially useful for treatment of T cell-mediated autoimmune
      diseases.

PMID- 15154872
TI  - Functional modulation of activated lymphocytes by time-varying magnetic fields.
AB  - Time-varying magnetic fields (TVMF), especially those of extremely low frequency
      (below 250 Hz), have been reported to have profound effects on biological systems
      due to the induced currents since the biological systems consist of electrolyte
      solution. We have been interested in utilizing TVMF for cellular
      immunomodulations, and have shown that the TVMF could augment macrophage
      activation. In this study, the effect of TVMF on lymphocyte activation was
      studied. Murine spleen lymphocytes were isolated from DDY mice and incubated in
      the presence of Concanavalin A (ConA) for 72 h. The lymphocytes were exposed to
      TVMF for various durations, from 20 min to 2 h. The proliferation activities of
      lymphocytes were assayed by ELISA by use of 5-bromo-2'-deoxy-uridine Labeling and
      Detection Kit III (Roche Diagnostic Corp. Indianapolis, IN, USA). The IL1beta and
      IL2 concentrations in the culture medium were measured by ELISA assay. The IL2
      receptor expression on the lymphocytes was evaluated by FACS analysis by use of
      FITC-conjugated monoclonal antibody. The proliferation activities were
      significantly enhanced by the TVMF for up to 40 min exposure from the initiation
      of ConA stimulation. The degree of augmentation effects, defined by the ratio of
      activation index of with and without TVMF, was varied from 1.1 to 2.7, and
      related to the lymphocyte responsiveness to the ConA. The less responsive cells
      showed more TVMF augmentation effects. The TVMF exposure after 40 min from ConA
      addition showed no effect, suggesting that the TVMF effects are most likely
      related to the Ca ion influx. The prolonged exposure of TVMF depressed the
      augmentation effects, which was caused by the depressed IL-2 receptor expression
      although both IL1-beta and IL-2 productions were not affected.

PMID- 15154871
TI  - Filtration leukocytapheresis therapy in the treatment of rheumatoid arthritis
      patients resistant to or failed with methotrexate.
AB  - Filtration leukocytapheresis (LCP) is a treatment for abnormal autoimmune states,
      which removes responsible leukocytes from the peripheral blood. To examine the
      efficacy of LCP therapy in the treatment of rheumatoid arthritis (RA), nine
      patients were selected, who were either resistant to methotrexate, or failed with
      methotrexate due to drug ineffectiveness or adverse side effects. For these
      patients, LCP therapy was performed once a week for five weeks. After five LCP
      treatments, the patients were observed for 12 weeks, to test the efficacy of the
      treatment. The definition of improvement given by the American College of
      Rheumatology (ACR core set) was used for efficacy evaluation of LCP therapy. As
      the result, 77.8% of the patients showed an ACR 20% response and 44.4% of the
      patients showed an ACR 50% response. With improvement of joint symptoms, IL-6 was
      significantly decreased at 8 weeks and 12 weeks after the treatment. The
      expression of adhesion molecules CD11a, CD11b, and CD18 on granulocytes decreased
      directly after the LCP treatment. No adverse side effect was monitored during the
      study period. These results indicates that LCP treatment is a useful treatment
      for RA patients who were resistant to methotrexate, or failed with methotrexate
      due to ineffectiveness or side effects of the drug.

PMID- 15154873
TI  - Efficacy of granulocytapheresis and leukocytapheresis for the treatment of
      microscopic polyangiitis.
AB  - We evaluated the efficacy of granulocytaperesis and leukocytapheresis for the
      treatment of rapidly progressive glomerulonephritis (RPGN) and lung hemorrhage
      caused by microscopic polyangiitis. Three patients with RPGN were treated by
      granulocytapheresis (GCAP) and five patients with RPGN were treated by
      leukocytapheresis (LCAP). The prednisolone dose was 0.4 +/- 0.2 g/kg/day (mean +/
      SD; range 0.2-0.8 g/kg/day). Pre-treatment serum creatinine was 3.2 +/- 1.4
      mg/dL (1.4-5.1 mg/dL). The patients were followed for a mean period of 15 +/- 6
      months (6-23 months). Renal function improved in five of the eight RPGN patients.
      Three lung hemorrhage episodes in two different patients were treated with GCAP
      and one lung hemorrhage episode was treated with LCAP combined with various doses
      of corticosteroids. All four lung hemorrhage episodes were ameliorated. We
      concluded that combined therapy of GCAP or LCAP and corticosteroids is effective
      for the treatment of RPGN and lung hemorrhage due to microscopic polyangiitis.

PMID- 15154874
TI  - Extracorporeal albumin dialysis.
AB  - Previous studies reported that dialysis with albumin dialysate (AD) was effective
      in removing albumin-binding toxins (ABT), and the Molecular Adsorption Recycling
      System (MARS) and Continuous Albumin Purification System (CAPS) have been
      developed. These blood purification therapies were categorized into the concept
      of extracorporeal albumin dialysis (ECAD). ECAD is defined as extracorporeal
      therapies using AD for the removal of not only water-soluble but also ABT. It was
      reported that symmetric as well as asymmetric membrane dialyzers had the effect
      of the removal of bilirubin by AD. The larger pore size membrane can remove more
      bilirubin. In the greater albumin concentration in AD, the removal capacity for
      bilirubin by AD increased. Bilirubin in AD could be removed by a charcoal and a
      bilirubin adsorption column, and its concentration in AD remained approximately
      constant. In clinical performance of CAPS, cellulose triacetate membrane, 5% AD,
      bilirubin adsorber columns, and charcoal adsorber columns were used. This system
      was applied continuously for 24 h for treatment. CAPS could control not only
      renal but also liver function during the 24 h, without any adverse effect. MARS
      removes many toxic substances including ABT, and has beneficial effect on brain,
      liver, renal, and cardiovascular functions, and improvement of 30-day survival
      were reported. ECAD may become a possible therapeutic tool in patients with the
      disease state of ABT accumulation as an artificial kidney and liver. However,
      several attempts such as the application of recombinant human albumin and acetate
      free dialysate, should be required.

PMID- 15154875
TI  - A case of chronic relapsing ANCA-associated microscopic polyangiitis successfully
      treated with plasma exchange.
AB  - We report the case of a 4.5-year-old girl with microscopic polyangiitis (MPA)
      manifesting antineutrophil cytoplasmic autoantibody (ANCA)-positive necrotizing
      crescentic glomerulonephritis and pulmonary hemorrhage. She was initially on
      induction therapy with corticosteroids and azathioprine. Plasma exchange (PE)
      combined with immunosuppressants was used to treat an episode of recurrent
      pulmonary hemorrhage, and achieved remission. At 9.8 years of age her kidney
      disease relapsed, associated with renal dysfunction and increased proteinuria. To
      minimize the toxic effects of immunosuppressants, she was treated with PE again,
      and her renal dysfunction resolved. Plasma exchange was effective in reducing the
      risk of death and preserving long-term renal function without the severe adverse
      effects of immunosuppressants. Our preliminary results indicate that PE is likely
      to be a treatment option for children in acute phase of ANCA-associated MPA, who
      should be protected from the toxic effects of immunosuppressants.

PMID- 15154876
TI  - A case report of the efficacy of apheresis for refractory autoimmune
      thrombocytopenia in a patient with systemic lupus erythematosus associated
      hemolytic anemia.
AB  - Autoantibodies against platelets are found in patients with autoimmune
      thrombocytopenic purpura (AITP) as well as in thrombocytopenia associated with
      systemic lupus erythematosus (SLE). The high titer of platelet associated
      immunoglobulin G (PA IgG) suggests the presence of antibodies against platelets.
      Platelet associated antibodies are thought to play a major role in the
      pathogenesis of autoimmune thrombocytopenia. There is a possibility that double
      filtration plasmapheresis (DFPP) is effective in removing the antibodies against
      platelets from the peripheral blood. It is suggested that DFPP may reinforce the
      efforts of the conventional treatment, especially high-dose intravenous
      immunoglobulin therapy (IVIg). DFPP was performed for severe thrombocytopenia on
      a SLE patient with high PA IgG value, refractory to the conventional therapy
      including corticosteroid therapy and IVIg. The patient underwent three sessions
      of DFPP combined with IVIg and the corticosteroid therapy immediately before the
      initiation of IVIg. The severe thrombocytopenia improved drastically after the
      combination treatment, accompanied with the decrease of the PA IgG titer. It was
      suggested that DFPP combined with corticosteroid and IVIg was effective for
      severe autoimmune thrombocytopenia on SLE patients refractory to the conventional
      therapies.

PMID- 15154877
TI  - Protective effect of an oral adsorbent on renal function in chronic renal
      failure: determinants of its efficacy in diabetic nephropathy.
AB  - Large-scale clinical trials have shown that the oral adsorbent AST-120 improves
      renal function and delays the initiation of dialysis in chronic renal failure
      (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via
      common mechanisms, then the same effects can be expected in diabetic nephropathy.
      However, no study on diabetic nephropathy has been reported. Thus, we enrolled
      patients with statistically significant progression of CRF secondary to diabetic
      nephropathy, and analyzed the changes in renal function after AST-120 therapy,
      and the clinical factors associated with response to therapy. We enrolled 276
      patients with diabetic nephropathy, whose serum creatinine (Scr) had increased
      from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These
      patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical
      data were analyzed by dividing the patients into three groups based on the
      changes in Scr after AST-120 therapy, with responders showing a decrease (N =
      82), partial responders showing <1.5-fold increase (N = 144), and non-responders
      showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of
      1/Scr-time line, suggesting that AST-120 suppressed the progression of renal
      impairment. No responders required dialysis, whereas 24.3% of the partial
      responders and 36.0% of the non-responders started dialysis therapy. In
      responders, the 1/Scr-time slope showed a negative-to-positive shift and serum
      urea nitrogen decreased significantly, whereas the improvement was moderate in
      partial responders and minimal in non-responders. Among responders, AST-120
      therapy significantly improved renal function despite the presence of
      hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The
      beneficial effect of AST-120 was significantly more marked in patients with blood
      pressure controlled within the normal ranges and hematocrit maintained at 30% or
      above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis
      therapy in patients with progressive aggravation of CRF secondary to diabetic
      nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and
      hypertension. Active use of AST-120 may be recommended in patients with good
      control of blood pressure and hematocrit above 30%.

PMID- 15154878
TI  - Inhibitory effects of etidronate on the progression of vascular calcification in
      hemodialysis patients.
AB  - The present study was designed to determine if etidronate inhibits the
      development of aortic calcification in hemodialysis (HD) patients. Eighteen
      Japanese HD patients were divided randomly into etidronate-treated or control
      groups. Etidronate was given orally at the dose of 200 mg just before sleep on
      the day of dialysis, which was performed three times per week. In the control
      group, the aortic calcification area (ACA) increased after 6 months. In the
      patients who received etidronate, however, when compared to the control group,
      increases in ACA were significantly suppressed. Serum Ca, P, and the Ca x P
      product did not change during etidronate treatment. These results suggest that
      etidronate inhibits the progression of vascular calcification without changes in
      serum Ca and P levels.

PMID- 15154879
TI  - Tryptophan-immobilized column-based immunoadsorption as the choice method for
      plasmapheresis in Guillain-Barre syndrome.
AB  - Plasmapheresis is widely performed as treatment for patients with Guillain-Barre
      syndrome (GBS) in the acute phase. As tryptophan-immobilized column-based
      immunoadsorption (Tr-IA) is a safer method than either double-filtration
      plasmapheresis (DFPP) or plasma exchange (PE), we investigated whether or not Tr
      IA is as effective as other methods, and should be selected as the procedure of
      choice in patients with GBS. We retrospectively compared clinical outcomes, using
      Hughes grading, in GBS patients treated with Tr-IA, DFPP or PE. The outcome in
      the Tr-IA group was also compared historically with patients treated by PE in
      seven previous studies. We studied 34 patients with GBS: 20 were treated with Tr
      IA, 11 with DFPP, and 3 with PE. The age, sex, duration from onset to initiation
      of treatment, and Hughes grade at entry did not differ among the Tr-IA, DFPP and
      PE groups. There was no significant difference in outcomes among these three
      groups, nor was there a significant difference between the outcomes in the Tr-IA
      and DFPP groups with respect to subgroups of Hughes grade at entry. Also, our Tr
      IA group did not show a different outcome from the previously reported patients
      treated with PE. The frequency of complications in our Tr-IA group is
      significantly lower than that in both our DFPP group, and in the previously
      reported cases of patients treated with PE. Tr-IA, DFPP and PE have almost the
      same efficacy in patients with GBS, but Tr-IA is recommended as the
      plasmapheresis method of choice because of its safety.

PMID- 15154880
TI  - Twice daily plasma exchange in refractory thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) usually responds to daily single total
      plasma exchange (TPE) or to plasma infusion. However, some cases are refractory
      to total plasma exchange, and additional efficacious treatment may not be
      available. A 34-year-old white male diagnosed with TTP was found to be refractory
      to single TPE. Steroids and twice daily TPE, in addition to splenectomy and
      vincristine, worked well to prevent further clinical deterioration. Laboratory
      values were normalized at the completion of treatment protocol. Cases of TTP
      refractory to single TPE/day may benefit from early treatment of twice-daily TPE
      in addition to a combination therapy of steroids, splenectomy, and vincristine.

PMID- 15154881
TI  - A possible involvement of the carboxymethylation process in carpal tunnel
      syndrome in hemodialysis patients.
AB  - A median motor nerve latency (DML) is generally prolonged in the carpal tunnel
      syndrome (CTS) of hemodialysis patients. Meanwhile, the advanced glycation
      process of proteins has been reported to be involved in the pathogenesis of the
      dialysis related amyloidosis. To investigate the role of carboxymethylation in
      dialysis related CTS, we measured a circulating carboxymethyllysine-hemoglobin
      (CML-Hb) level and nerve conduction velocity in 44 hemodialysis patients. The
      circulating CML-Hb level was 6.56 +/- 3.18 nmol CML/mg Hb, median motor nerve
      conduction velocity (NCV) was 49.8 +/- 4.64 m/s, median DML was 4.44 +/- 1.06 ms,
      and difference between median DML and ulnar DML (Delta DML) was 1.68 +/- 1.09 ms.
      Median and ulnar nerve NCV showed no correlation with circulating CML-Hb level.
      Both median DML and Delta DML were significantly correlated with CML-Hb (r =
      0.429, P = 0.003, r = 0.472, P = 0.001). This study provided additional clinical
      evidence of an involvement of an advanced glycation process in the pathogenesis
      in CTS in hemodialysis patients.

PMID- 15154884
TI  - Production and consumption of science in a global context.

PMID- 15154885
TI  - Failure to rescue: lessons from missed opportunities in care.

PMID- 15154886
TI  - Gender, power, nursing: a case analysis.
AB  - This paper is concerned with events that were the subject of an inquest into the
      deaths of 12 children who died while undergoing or shortly after having undergone
      cardiac surgery at the Winnipeg Health Sciences Centre, Manitoba, Canada, during
      1994. A notable finding of the Sinclair Inquest was that nurses involved with the
      pediatric cardiac surgery program were concerned about the competence of the
      surgeon and made sustained efforts throughout 1994 to have these concerns
      addressed. That the nurses' concerns were not taken seriously is the central
      problem of this paper. Essentially, the position articulated is that gendered and
      gendering discourses constituted a form of power that structured the field of
      nurses' possible actions. These discourses constituted a resource to make nurses
      knowable, to produce them as certain forms of the person, and were therefore part
      of what governed nurses everyday conduct. Though neither simply good nor bad in
      themselves, in this case, these discourses had constraining effects on how nurses
      were able to conduct themselves.

PMID- 15154887
TI  - Holding American hospitals accountable: rhetoric and reality.
AB  - Assessing the vast arena that continues to grow in pursuit of accountability in
      American hospitals, this paper raises the following question: Is this enterprise
      geared toward making hospitals better or toward making them only look better?
      'Accountability' has become an umbrella concept to signal the need to demonstrate
      - to others - that performance is being measured and perfected. The author
      asserts that there is an imperfect fit between health-care and the industrial
      model being used to measure quality of care due to four problematic issues: the
      nature of contemporary patient care, the overstating and overselling of
      accountability proposals, inflated expectations placed upon 'rationalization',
      and insufficient attention afforded accident and error. The paper concludes with
      a plea for reconsideration of the tilt toward a business approach to health-care,
      asking if, in our zeal to hold hospitals accountable, we are measuring what is
      important or simply making important what we can measure.

PMID- 15154888
TI  - The heart of the art: emotional intelligence in nurse education.
AB  - The concept of emotional intelligence has grown in popularity over the last two
      decades, generating interest both at a social and a professional level.
      Concurrent developments in nursing relate to the recognition of the impact of
      self-awareness and reflexive practice on the quality of the patient experience
      and the drive toward evidence-based patient centred models of care. The move of
      nurse training into higher education heralded many changes and indeed challenges
      for the profession as a whole. Traditionally, nurse education has been viewed as
      an essentialist education, the main emphasis being on fitness for practice and
      the statutory competencies. However, the transfer into the academy confronts the
      very notion of what constitutes this fitness for practice. Many curricula now
      make reference in some way to the notion of an emotionally intelligent
      practitioner, one for whom theory, practice and research are inextricably bound
      up with tacit and experiential knowledge. In this paper we argue that much of
      what is described within curriculum documentation is little more than rhetoric
      when the surface is scratched. Further, we propose that some educationalists and
      practitioners have embraced the concept of emotional intelligence uncritically,
      and without fully grasping the entirety of its meaning and application. We
      attempt to make explicit the manner in which emotional intelligence can be more
      realistically and appropriately integrated into the profession and conclude by
      suggesting a model of transformatory learning for nurse education.

PMID- 15154889
TI  - Making room for grief: walking backwards and living forward.
AB  - In this paper, the authors describe an aspect of a program of research around
      grief and clinical practice. The first phase of the study involves examination of
      experiences of grief with attention to troublesome or problematic beliefs that
      fuel the extent of suffering in the bereaved. The data, obtained from a review of
      videotaped clinical interviews with families seen in the Family Nursing Unit at
      the University of Calgary, were analyzed according to philosophical hermeneutic
      tradition. Findings suggest that grief is an experience that is ongoing, that
      changes in nature over time, but that involves a continuing relationship with the
      deceased; it is a graceful, periodic, deliberate walk backwards while keeping a
      sure foot in living forward.

PMID- 15154890
TI  - Why 4 years when 3 will do? Enhanced knowledge for rural nursing practice.
AB  - In Australia, debates over the appropriate length of undergraduate nursing
      programs have a long history. Submissions from both universities and industry to
      key government reports have consistently argued that the current minimum entry
      level of practice, a three-year program, is too short to enable students to gain
      the knowledge and skills necessary for the contemporary nursing role. Despite
      these submissions, the established entry level for nursing practice in Australia
      remains a three-year undergraduate bachelor degree. However, there is a small
      group of high-achieving students who will begin practice at the end of a four
      year program. Little is known about these programs, or the students who are
      currently enrolled in them. Designed as a collaborative endeavour, based on co
      operative inquiry, the study discussed in this article aimed to provide an
      insight into aspects of a four-year undergraduate nursing program. Potentially,
      the broader theoretical and clinical preparation that is possible in a four-year
      program provides students with enhanced learning opportunities that will enable
      them to graduate with more confidence and greater ability. In this study a four
      year program provided an opportunity for a regional university to prepare
      students for the demanding realities of a complex area of practice, rural
      nursing.

PMID- 15154891
TI  - Response to 'The influence of liberal, political ideology on nursing science', an
      article by Annette J. Browne (2001).

PMID- 15154896
TI  - Educating nursing students as individuals.

PMID- 15154898
TI  - Reflection in preregistration nursing curricula.
AB  - BACKGROUND: The concepts of reflection and reflective practice are increasingly
      popular themes in the nursing literature. Reflective practice has been advocated
      as a method for overcoming the divergence between nursing theory and practice,
      and as a means of articulating and developing knowledge embedded in practice.
      However, these claims are based more on theoretical debate than research
      evidence. In common with other regulatory bodies, the Irish regulatory nursing
      body advocates the need for reflective nurses, and curricula are being adapted to
      reflect this. These changes are taking place when there is still little guidance
      on the teaching or assessment of reflective practice. Given the lack of research
      on the topic and the need for evidence on which to base the teaching of
      reflective practice, a descriptive exploratory study was undertaken. AIM: The aim
      of this paper is to report how a group of nurse teachers perceived and
      interpreted reflective practice in preregistration nursing curricula in schools
      of nursing in The Republic of Ireland. METHODS: Data were collected using a
      postal questionnaire distributed to all schools of nursing involved in the
      preregistration diploma in nursing (n = 40). RESULTS: The results indicate
      variation between institutions in the number of hours allocated to the subject
      and where reflective practice was included in the curriculum. Emphasis was placed
      on theoretical models of reflection as opposed to the process or the skills
      required to become a reflective practitioner. Lecture and group discussion were
      the dominant teaching methods. Additionally, a number of teachers expressed
      dissatisfaction with the preparation they had received to teach the subject, and
      identified some of the challenges they experience when teaching reflective
      practice. CONCLUSIONS: The results provide a focus for further debate amongst
      nurse educators involved in implementing reflective practice in the curriculum.
      The results are limited by a response rate of 50% and by the geographic setting.
      Further research is needed to substantiate the findings of the study. However,
      there results do suggest that there is a need to clarify curricular content in
      relation to reflective practice and prepare nurse tutors for their role in
      teaching this subject more effectively.

PMID- 15154899
TI  - Cognitive dissonance and undergraduate nursing students' knowledge of, and
      attitudes about, smoking.
AB  - BACKGROUND: Smoking is a major cause of morbidity and mortality. Although nurses
      have an important role in health promotion, and are well placed to see the
      harmful effects of tobacco smoking, studies suggest that they smoke at much the
      same rate as the general population. AIM: The aim of this paper is to report a
      study examining undergraduate nursing students' knowledge about the impact of
      smoking on health, and their attitudes towards smokers and smoking. METHODS: The
      study took place in 2001, using a non-probability sample of 366 undergraduate
      nursing students from an Australian university. Participants completed the
      Smoking and Health Promotion instrument. Festinger's theory of cognitive
      dissonance provided an explanatory framework for the findings. RESULTS: Most
      respondents who were still smoking began the habit while in high school. Students
      had greater generic than specialized knowledge about the effects of smoking on
      health, and there was no significant difference between second and third year
      students' knowledge. Those who still smoked had less favourable attitudes towards
      smoking-related health promotion than those who had never smoked or stopped
      smoking. Non-smokers were more supportive of non-smokers' rights than those who
      continued to smoke, while those who had stopped smoking were undecided. There was
      minimal association between levels of knowledge and attitudes about being
      sensitive to smoking-related health risks. CONCLUSION: The findings have
      implications for both high school education and undergraduate nursing education,
      and for the recruitment of students to undergraduate nursing programmes. More
      attention needs to be given in undergraduate nursing programmes to smoking and
      smoking-related illnesses, and to nurses' role in smoking health promotion.

PMID- 15154900
TI  - Making portfolios work in practice.
AB  - BACKGROUND: A portfolio captures learning from experience, enables an assessor to
      measure student learning, acts as a tool for reflective thinking, illustrates
      critical analytical skills and evidence of self-directed learning and provides a
      collection of detailed evidence of a person's competence. AIMS: This paper
      reports data on how assessors and nursing students match learning outcomes and/or
      competencies to their practice and then reconstruct those experiences into the
      format required by the portfolio documentation. The data were gathered as part of
      a larger study to evaluate the use of portfolios in the assessment of learning
      and competence in England. METHODS: This three phase stakeholder evaluation was
      designed to gain the views of those involved in designing, implementing and using
      portfolios in nurse education. In phase 2, 122 students and 58 nurse teachers
      were interviewed about their perceptions of portfolio use, and a further 32
      students and 26 assessors were interviewed after they had been observed taking
      part in an assessment process. Thematic data analysis was used. FINDINGS:
      Assessors and students underwent a complex process of deconstructing learning
      outcomes/competences to fit these to their practice. These then had to be
      reconstructed through the written medium to fit the structure of the portfolio.
      Confirmation that this met teachers' expectations was essential to allay feelings
      of insecurity. CONCLUSIONS: To achieve maximum benefit from the portfolio as a
      learning tool to link theory and practice, there needs to be a clear fit between
      the model of portfolio and the professional practice that is to be assessed.
      Outcomes and competences, as well as the type of evidence required to demonstrate
      their achievement, and integration of the whole experience should match the
      students' stage of professional and academic development. Over-complex approaches
      to practice assessment, particularly in the early stages of students' careers,
      can detract from clinical learning in favour of learning how to complete the
      portfolio successfully.

PMID- 15154901
TI  - Abuse-related post-traumatic stress during the childbearing year.
AB  - BACKGROUND: Women with abuse-related post-traumatic stress who are pregnant
      experience symptoms that nurses and midwives may not recognize or know how to
      respond to. AIM: The purpose of this article is to increase familiarity with the
      post-traumatic stress disorder diagnostic framework by illustrating the symptom
      categories and associated features with women's descriptions of the symptoms from
      qualitative interviews. METHODS: A secondary analysis was performed with data
      from a qualitative interview study of the maternity care experiences of 15
      American women who had abuse-related post-traumatic stress during pregnancy.
      Content analysis was used to extract all participant statements describing how
      post-traumatic stress disorder symptoms and associated features manifested in
      pregnancy. These were then juxtaposed with the post-traumatic stress disorder
      diagnostic framework. RESULTS: Participants' interviews included a range of
      descriptions of the intrusive re-experiencing, avoidance and numbing, and
      hyperarousal core symptoms of post-traumatic stress disorder, as well as
      associated psychological features such as somatization, dissociation and
      interpersonal sensitivity, and associated behavioural features such as substance
      abuse, disordered eating, high-risk sexual behaviours, suicidality, and
      revictimization. CONCLUSIONS: Limitations of this study include that it is a
      secondary analysis, using a small North American sample, and focusing only on
      abuse-related post-traumatic stress disorder. Descriptive information from this
      qualitative study may bridge the gaps between psychiatric technical language,
      women's subjective experiences, and clinicians' perceptions of a woman's post
      traumatic stress reactions.

PMID- 15154903
TI  - Spiritual perspectives, needs and nursing interventions of Christian African
      Americans.
AB  - BACKGROUND: Although the amount of literature on spiritual needs and care has
      increased, in practice there has been little change in how nurses assess
      spiritual need. This suggests that not all spiritual needs of patients are being
      addressed. Based on the assumption that spiritual needs vary by culture, this
      study focused on one subgroup, namely Christian African-Americans. AIMS: The aim
      of this paper is to report a study examining spiritual perspectives, spiritual
      needs and desired nursing interventions during hospitalization identified by
      Christian African-Americans. METHODS: A descriptive correlational design was
      employed. A convenience sample (n = 44) was recruited from three African-American
      churches. Descriptive statistics were calculated, and one-way anovas used to
      examine spiritual perspectives and spiritual values. Content analysis was used to
      analyse and summarize qualitative data. Instruments included the Spiritual
      Perspective Scale (SPS) and two open-ended questions. RESULTS: The mean age of
      participants was 56 years (range 19-84). The majority was female (86%); 71% of
      respondents strongly agreed that they had spiritual needs to be met during
      hospitalization. Mean score for the SPS was 5.7 (sd = 0.36). Respondents used a
      total of 103 phrases to describe spiritual needs, based on three dimensions of
      connectedness: connectedness to God (50 phrases), connectedness to others (37
      phrases) and connectedness to self (16 phrases). Desired nursing interventions
      included: participating in spiritual activities (n = 41); demonstrating caring
      qualities (n = 27); providing comforting measures (n = 13); providing reassurance
      (n = 9); recognizing the spiritual caregiver role (n = 7); and incorporating
      diversity in care (n = 3). CONCLUSIONS: The findings provide information for
      nurses to facilitate development of culturally appropriate spiritual nursing
      interventions.

PMID- 15154902
TI  - Smoking habits and predictors of continued smoking in patients with acute
      coronary syndromes.
AB  - BACKGROUND: Most patients with acute coronary syndrome quit smoking when
      hospitalized, although several have been found to relapse and resume smoking
      within 3 months. AIM: This paper reports a study to identify factors that can
      predict who will resume smoking after hospitalization for an acute coronary
      syndrome. METHODS: Patients (n = 1320) below the age of 75 years, admitted to a
      Swedish university hospital coronary care unit with acute coronary syndromes,
      between September 1995 and September 1999, were consecutively included. Data were
      collected from hospital medical records and included information on previous
      clinical history, former illnesses and smoking. During their hospitalization, an
      experienced nurse interviewed the patients by using a structured questionnaire to
      obtain additional information. Patients were followed up 3 months after the
      discharge. Those who continued to smoke (non-quitters) were compared with those
      who had stopped (quitters) with regard to age, sex, medical history, clinical
      course, and intention to quit. To identify factors independently related to
      continued smoking, a logistical regression in a formal forward stepwise mode was
      used. RESULTS: Of the patients admitted, 33% were current smokers. Three months
      after discharge, 51% of these patients were still smoking. There were no
      significant differences in age, gender or marital status between non-quitters and
      quitters. In a multivariate analysis, independent predictors of continued smoking
      were: non-participation in the heart rehabilitation programme (P = 0.0008); use
      of sedatives/antidepressants at time of admission (P = 0.001); history of
      cerebral vascular disease (P = 0.002), history of previous cardiac event (P =
      0.01); history of smoking-related pulmonary disease (P = 0.03) and cigarette
      consumption at index (P = 0.03). CONCLUSIONS: Smoking patients who do not
      participate in a heart rehabilitation programme may need extra help with smoking
      cessation. The findings may provide means of identifying patients in need of
      special intervention.

PMID- 15154904
TI  - Postoperative complications in the first 24 hours: a general surgery audit.
AB  - BACKGROUND: Traditionally, the purpose of routine postoperative surveillance has
      been to detect postoperative complications. The literature reports well
      documented, procedure-specific postoperative complication rates. However, there
      are no reports detailing the prevalence of postoperative complications in general
      surgical ward settings, where nurses care for patients following a variety of
      surgical procedures. AIMS: This paper reports an audit of the frequency and type
      of postoperative complications in a general surgical population occurring in the
      first 24 hours postoperatively. METHOD: A patient record audit was undertaken for
      all postoperative patients who returned to two general surgical wards. This was
      conducted sequentially, involving a 4 week data collection phase in each
      participating ward during 2001. RESULTS: The audit sample comprised 144 patient
      records with an average patient age of 54 years. Statistically significant
      results included the rate of postoperative nausea and vomiting of 37.5% (n = 54),
      and 17% (n = 25) of patients experiencing another 'clinical event'. LIMITATIONS:
      The findings reflect only those complications recorded/documented in
      postoperative patients' records, and cannot be generalized beyond the sample and
      setting. CONCLUSIONS: Postoperative patients cared for on general surgical wards
      experienced a high level of nausea and vomiting, while the occurrence of life
      threatening complications was small.

PMID- 15154905
TI  - Women's experience of endometriosis.
AB  - BACKGROUND: Endometriosis is a chronic disease affecting between 5% and 15% of
      women of reproductive age. Diagnosis can be delayed for many years, despite the
      existence of severe pain, and women often find that their experiences are not
      taken seriously by health professionals. Little research has been conducted into
      how endometriosis affects their lives. AIM: The aim of this paper is to report a
      study exploring women's experience of living with endometriosis. METHOD: A
      qualitative approach was used, in which women were asked to relate their stories
      starting from the first experience of symptoms that they associated with
      endometriosis. Key areas to be followed-up during interviews were identified by
      women with endometriosis who were not participants. Fifteen semi-focused
      interviews were conducted, and thematic and content analysis were carried out
      using the identified key areas, and themes elicited from initial analysis of the
      interview transcripts. From these two processes the final themes of delay in
      diagnosis, pain, dyspareunia, treatment, work and social relationships, the
      workplace, and the future emerged. FINDINGS: Despite the existence of severe
      pain, often described as 'intense' or 'overwhelming', women experienced delay in
      receiving a diagnosis of endometriosis, and their symptoms were frequently
      trivialized or normalized. This, and the limited effectiveness of treatments,
      affected relationships with partners and family, work, and sexual relations,
      although individual experiences in each area were diverse. CONCLUSION: The
      experience of endometriosis pervades all aspects of a woman's life. This
      experience is compounded by the side effects of many treatments. Women with this
      disease need to be taken seriously, and not have their pain trivialized or
      normalized. Nurses are often well-placed to assist patients in receiving
      sensitive and appropriate care.

PMID- 15154906
TI  - 'The good nurse': visions and values in images of the nurse.
AB  - BACKGROUND: The various ways in which the nurse has been publicly portrayed do
      not merely reflect the value of nursing in society, but also define the
      boundaries of nursing, and reveal the ideologies and systems of power-brokerage
      at work in shaping nursing. Therefore, it is of profound interest to the
      profession to continue to examine the ways in which the nurse is and has been
      portrayed. AIM: This paper aims to present a historical analysis of the image of
      the nurse in public discourses in Ireland. METHODS: Using a framework of critical
      discourse analysis within the method of historical research, the paper draws on
      documentary primary sources to present an analysis of discourse concerning the
      'good nurse'. FINDINGS: In exposing the diverse ways in which the nurse has been
      depicted in Irish public discourses, the origins of the 'good nurse' ideal are
      identified, the reasons for its continued promotion are critically examined, and
      the effects of the ideal on the development of nursing in Ireland are considered.
      CONCLUSIONS: While the ways in which Irish nurses have been depicted in public
      discourses have similarities with international nursing imagery, the 'good nurse'
      ideal has a uniquely Irish expression, indicating that the image of the nurse is
      both culture-specific and changes to reflect the underlying sociocultural
      context, and prevailing system of political power and influence.

PMID- 15154910
TI  - International Journal of Experimental Pathology moves online for submission and
      peer review.

PMID- 15154907
TI  - Towards a Chinese definition of nursing.
AB  - BACKGROUND: A theory of nursing derived from nurses' experience can reflect
      indigenous practice values, which in turn can act as a fertile source of ideas
      and inventiveness in developing a relevant knowledge base to inform practice.
      However, systematic study of how Chinese nurses articulate nursing in their
      everyday practice is lacking. AIM: The aim of this paper is to describe how
      Chinese nurses conceptualize the practice of nursing; and to arrive at a
      definition of nursing based on this common understanding. METHOD: A systematic
      inquiry using a modified version of Van Kaam's controlled explication was
      designed. In the prescientific phase, 254 written accounts of nurses' views on
      nursing as lived in their everyday practice were collected in eight Chinese
      cities. In the scientific phase, concept analysis based on Aristotle's notion of
      four causes was adopted to capture the richness of the phrases that explain the
      multi-dimensionality of Chinese nurses' concepts of nursing. This was followed by
      a survey of 1782 nurses to verify the findings. The most commonly held views were
      summarized and a Chinese definition of nursing was drafted. FINDINGS: Nursing in
      the Chinese sense means to understand the dynamic health status of a person, to
      verify health concerns dialectically, and to consider interventions with the goal
      of assisting the person to master the appropriate health knowledge and skills for
      the attainment of optimal well-being. The survey findings show that nursing has
      developed into a professional caring practice in China today. The definition has
      some similarities with those of Western nurses, but the underpinning epistemic
      concerns are grounded in the philosophy of traditional Chinese medicine and
      Eastern ideologies. CONCLUSION: The findings provide Chinese nurses with a
      definition of nursing articulated in their own language. The identification of
      qing, li, zhi, and xin as its epistemic concerns, and the articulation of the
      process of nursing as 'dialectical verification', provides a perspective for
      understanding nursing based on Eastern philosophies. The findings can enhance
      nurses' engagement in a cross-cultural dialogue to promote better understanding
      of nursing as it is practised in different parts of the world.

PMID- 15154912
TI  - Characterization of the E-cadherin/catenin complex in colorectal carcinoma cell
      lines.
AB  - The E-cadherin/catenin complex is a prime mediator of cell-cell adhesion. APC
      mutations can result in loss of beta-catenin downregulation and an accumulation
      of beta-catenin in the cell. Beta-CATENIN mutations can have a similar effect.
      The aim of this study was to investigate the effect of beta-CATENIN and APC
      mutations on the expression and assembly of the E-cadherin/catenin complex. Five
      colorectal carcinoma cell lines with different APC and beta-CATENIN gene status
      were selected and mutations were confirmed. The expression of members of the E
      cadherin/catenin complex was studied by immunohistochemistry and Western
      blotting. Complex assembly was investigated by immunoprecipitation. It is shown
      that E-cadherin and catenins are expressed in colorectal carcinoma cell lines
      with the predominant complex assembly being E-cadherin/beta-catenin/alpha
      catenin. The subcellular distribution of the proteins is influenced by cell-cell
      contact, resulting in membranous localization. The expression and assembly of the
      E-cadherin/catenin complex does not appear to be affected by the presence of APC
      and or beta-CATENIN mutations.

PMID- 15154911
TI  - Smad3 as a mediator of the fibrotic response.
AB  - Transforming growth factor-beta (TGF-beta) plays a central role in fibrosis,
      contributing to the influx and activation of inflammatory cells, the epithelial
      to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts
      and their subsequent elaboration of extracellular matrix. TGF-beta signals
      through transmembrane receptor serine/threonine kinases to activate novel
      signalling intermediates called Smad proteins, which modulate the transcription
      of target genes. The use of mice with a targeted deletion of Smad3, one of the
      two homologous proteins which signals from TGF-beta/activin, shows that most of
      the pro-fibrotic activities of TGF-beta are mediated by Smad3. Smad3 null
      inflammatory cells and fibroblasts do not respond to the chemotactic effects of
      TGF-beta and do not autoinduce TGF-beta. The loss of Smad3 also interferes with
      TGF-beta-mediated induction of EMT and genes for collagens, plasminogen activator
      inhibitor-1 and the tissue inhibitor of metalloprotease-1. Smad3 null mice are
      resistant to radiation-induced cutaneous fibrosis, bleomycin-induced pulmonary
      fibrosis, carbon tetrachloride-induced hepatic fibrosis as well as glomerular
      fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic
      conditions that are induced by EMT, such as proliferative vitreoretinopathy,
      ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral
      obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal
      models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of
      Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by
      overexpression of the inhibitory Smad7 protein or by treatment with the small
      molecule, halofuginone, dramatically reduces responses in animal models of
      kidney, lung, liver and radiation-induced fibrosis. Small moleucule inhibitors of
      Smad3 may have tremendous clinical potential in the treatment of pathological
      fibrotic diseases.

PMID- 15154913
TI  - Cholecystokinin blockade alters the systemic immune response in rats with acute
      pancreatitis.
AB  - Acute pancreatitis (AP) is characterized by initial pancreatic injury resulting
      from the activation of digestive enzymes and, later, widespread inflammation to
      distant organs. The aim of this study was to study whether the time-course of
      inflammatory events during AP induced by bile-pancreatic duct obstruction (BPDO)
      varies after lowering the acinar enzyme content by L364,718 (0.1 mg/kg/day)
      administration over 7 days before inducing AP. Flow cytometric immunophenotyping
      was used to analyse the following at different AP stages: distribution of major
      circulating leucocyte subsets, activation state of circulating neutrophils and
      monocytes as reflected by CD11b expression and tumour necrosis factor-alpha (TNF
      alpha) production and the contribution of T-cell-derived pro-(TNF-alpha) and anti
      (IL-10) inflammatory mediators. TNF-alpha plasma levels and neutrophil
      infiltration in pancreas and lung were also measured. At early BPDO times,
      L364,718 treatment partially inhibited leukocytosis and increase in peripheral
      blood neutrophils and monocytes as well as TNF-alpha expression by monocytes.
      However, from 6 h onwards after BPDO, L364,718 treatment was unable to prevent
      either pancreatic and lung neutrophil infiltration or the release of TNF-alpha
      from activated monocytes. By its action on circulating lymphocytes, L364,718
      treatment enhanced the severity of the inflammatory response induced by BPDO.
      Peripheral blood lymphocytes were recruited from earlier BPDO times, and 12 h
      after BPDO, T cells displayed a significantly higher reserve of TNF-alpha able to
      be released under stimulation but lower functional reserve of interleukin-10 (IL
      10) than observed in untreated rats. It is concluded that lowering the acinar
      enzyme content through L364,718 treatment prevents earlier systemic immune events
      in BPDO-induced AP. However, at the point of maximal injury, the inflammatory
      response became pronounced, largely due to the role played by activated T
      lymphocytes.

PMID- 15154915
TI  - Differential expression of p53, p63 and p73 protein and mRNA for DMBA-induced
      hamster buccal-pouch squamous-cell carcinomas.
AB  - Abnormalities in the p53 gene are regarded as the most consistent of the genetic
      abnormalities associated with oral squamous-cell carcinoma. Two related members
      of the p53 gene family, p73 and p63, have shown remarkable structural similarity
      to p53, suggesting possible functional and biological interactions. The purpose
      of this study was to investigate the differential expression of p73, p63 and p53
      genes for DMBA-induced hamster buccal-pouch squamous-cell carcinoma.
      Immunohistochemical analysis for protein expression and reverse transcriptase
      polymerase chain reaction (RT-PCR) for mRNA expression were performed for 40
      samples of hamster buccal pouches, the total being separated into one
      experimental group (15-week DMBA-treated; 20 animals) and two control groups
      (untreated and mineral oil-treated; 10 animals each). Using immunohistochemical
      techniques, nuclear staining of p53 and p73 proteins was detected in a subset of
      hamster buccal-pouch tissue specimens treated with DMBA for a period of 15 weeks,
      whereas p63 proteins were noted for all of the 20 hamster buccal-pouch tissue
      specimens treated with DMBA for 15 weeks as well as for all of the untreated and
      mineral oil-treated hamster buccal-pouch tissue specimens. Differential
      expression of p63, p73 and p53 protein for the experimental group was as follows:
      p63+/p73+/p53+ (n = 14; 70%); p63+/p73+/p53- (n = 2; 10%); p63+/p73-/p53- (n = 4;
      20%) and p63+/p73-/p53- (untreated [n = 10] and mineral oil-treated mucosa [n =
      10]; 100% each). Upon RT-PCR, DeltaNp63mRNA was detected within all of the 20
      hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks, whereas
      expression of TAp63 was not detected. Furthermore, p73 mRNA was identified for 16
      of the hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks,
      whereas p53 mRNA was noted for 14 15-week DMBA-treated pouches. The proportional
      (percentage) expression of DeltaNp63, p73 and p53 mRNA for the hamster buccal
      pouch tissue specimens treated with DMBA for 15 weeks was noted to be consistent
      with the findings using immunohistochemical techniques. A significant correlation
      between p53, p63 and p73 expression (protein and mRNA) was demonstrated for the
      hamster buccal-pouch carcinoma samples. Our results indicate that both p73 and
      p63 may be involved in the development of chemically induced hamster buccal-pouch
      carcinomas, perhaps in concert with p53.

PMID- 15154914
TI  - Cathepsin L-deficient mice exhibit abnormal skin and bone development and show
      increased resistance to osteoporosis following ovariectomy.
AB  - The role of cathepsin L in normal physiological processes was assessed using
      cathepsin L homozygous knockout mice (B6;129-Ctsl(tm1Alpk)). These mice were
      generated using gene targeting in embryonic stem cells. Null mice fail to express
      mRNA and protein to cathepsin L. They developed normally and were fertile. The
      distinct phenotypic change exhibited was a progressive hair loss, culminating in
      extensive alopecia by 9 months of age. Histological analysis of the skin from
      homozygous mice revealed diffuse epithelial hyperplasia, hypotrichosis, hair
      shaft fragmentation and utricle formation. These findings provide evidence that
      cathepsin L is involved in the regulation of epithelial cell proliferation and
      differentiation in the skin. In addition, the role of cathepsin L in bone
      remodelling was evaluated. Using bone histomorphometric measurements, trabecular,
      but not cortical, bone volume was found to be significantly decreased in the
      cathepsin L heterozygote and homozygote mice compared to the wild-type mice.
      Following ovariectomy, it was observed that loss of trabecular bone, the most
      metabolically active component of bone, occurred to a lesser extent in
      homozygote, and heterozygote mice, than was seen in wild-type mice. These
      observations suggest that cathepsin L is likely to have a role in controlling
      bone turnover during normal development and in pathological states.

PMID- 15154917
TI  - Apical periodontitis development and bacterial response to endodontic treatment.
      Experimental root canal infections in monkeys with selected bacterial strains.
AB  - In six monkeys, 160 root canals were inoculated with a combination of four
      bacterial strains belonging to species Streptococcus milleri, Peptostreptococcus
      anaerobius, Prevotella oralis, and Fusobacterium nucleatum. In two other monkeys,
      24 root canals were inoculated with a five-strain combination consisting of these
      strains and a strain of Enterococcus faecalis. All strains were previously
      isolated from an infected monkey root canal. After 8-12 months, survival of the
      strains was recorded bacteriologically, and the reaction in the periapical region
      was radiographed. From 180 of 184 root canals, one or more of the bacterial
      strains were reisolated. The two facultative strains were more frequently
      reisolated than the anaerobic strains. Apical periodontitis was registered in the
      periapical region of more than 96% of root canals with reisolated bacteria but in
      none of those without reisolated bacteria. Endodontic treatment was carried out
      in two sessions with an interval of 14 d without interappointment dressings, and
      the effect was evaluated bacteriologically before and after each treatment. The
      chemo-mechanical treatment reduced significantly the number of strains and
      bacterial cells. The facultative bacteria were more resistant to the treatment
      than the anaerobic bacteria. The five-strain combination had a higher survival
      rate than the four-strain combination.

PMID- 15154916
TI  - Reduced progression of atherosclerosis in apolipoprotein E-deficient mice treated
      with lacidipine is associated with a decreased susceptibility of low-density
      lipoprotein to oxidation.
AB  - A study has been carried out in the apolipoprotein (apo) E-deficient mouse to
      investigate the activity of lacidipine (a calcium antagonist with antioxidant
      properties) in inhibiting the development of atherosclerotic lesions; of
      particular interest were changes in the susceptibility of low-density
      lipoproteins (LDL) to oxidation. Mice receiving a Western-type diet to accelerate
      the development of atherosclerosis were treated orally with vehicle or lacidipine
      at 3 or 10 mg/kg/day for 8 weeks. Lacidipine treatment (at 3 or 10 mg/kg) had no
      effect on the plasma lipid profile. However, a significant (P < 0.01) dose
      related reduction of 43 and 50% of the aortic lesion area in respect to vehicle
      treated mice was observed. Moreover, the resistance of mouse plasma LDL to
      undergo lipid peroxidation was significantly (P < 0.01) increased in apo E
      deficient mice treated with lacidipine. The native LDL-like particle, derived
      from apo E-deficient mice treated with lacidipine, contained significantly lower
      concentrations of malonyldialdehyde than the vehicle-treated control group (P <
      0.01). After exposure to human umbilical vein endothelial cells, LDL-like
      particle vitamin E levels (expressed as area under the curve; AUC), were
      significantly higher (P < 0.01) in both the 3 and 10 mg/kg lacidipine-treated
      groups, in comparison with the vehicle-treated control animals. We conclude that
      lacidipine reduced the extent of the atherosclerotic area in
      hypercholesterolaemic apo E-deficient mice, and that this reduction may be
      associated with the capacity of the drug to decrease the susceptibility of LDL to
      oxidation.

PMID- 15154918
TI  - Gene expression signatures in chronic and aggressive periodontitis: a pilot
      study.
AB  - This pilot study examined gene expression signatures in pathological gingival
      tissues of subjects with chronic or aggressive periodontitis, and explored
      whether new subclasses of periodontitis can be identified based on gene
      expression profiles. A total of 14 patients, seven with chronic and seven with
      aggressive periodontitis, were examined with respect to clinical periodontal
      status, composition of subgingival bacterial plaque assessed by checkerboard
      hybridizations, and levels of serum IgG antibodies to periodontal bacteria
      assayed by checkerboard immunoblotting. In addition, at least two pathological
      pockets/patient were biopsied, processed for RNA extraction, amplification and
      labeling, and used to study gene expression using Affymetrix U-133 A arrays.
      Based on a total of 35 microarrays, no significantly different gene expression
      profiles appeared to emerge between chronic and aggressive periodontitis.
      However, a de novo grouping of the 14 subjects into two fairly robust clusters
      was possible based on similarities in gene expression. These two groups had
      similar clinical periodontal status and subgingival bacterial profiles, but
      differed significantly with respect to serum IgG levels against the important
      periodontal pathogens Porphyromonas gingivalis, Tannerella forsythensis and
      Campylobacter rectus. These early data point to the usefulness of gene expression
      profiling techniques in the identification of subclasses of periodontitis with
      common pathobiology.

PMID- 15154920
TI  - Influence of hydration and mechanical characterization of carious primary dentine
      using an ultra-micro indentation system (UMIS).
AB  - The conditions under which mechanical properties of dentine are tested influence
      the values recorded. The aims of this study were to examine the effect of
      hydration on the mechanical properties of primary carious dentine and to provide
      information on changes in hardness and modulus of elasticity change caused by the
      demineralizing caries process in dentine. Three primary molar teeth with
      untreated carious dentine were prepared for nano-indentation tests under both wet
      and dry conditions. Further tests were conducted on eight primary molars with
      untreated carious dentine under hydrated conditions. The mechanical properties of
      dehydrated carious dentine increased approximately 10-fold for hardness and 100
      fold for the modulus of elasticity compared with hydrated dentine. The hardness
      and elastic modulus of the carious primary dentine deteriorated progressively
      toward the lesion cavity floor, ranging from 0.001 to 0.52 GPa and from 0.015 to
      14.55 GPa, respectively, and could be fitted to a simple linear relationship when
      plotted in logarithmic scale vs. distance. The total depth of dentine affected
      was around 1100 microm parallel to the tubule direction. This depth was
      significantly greater than observed subjectively, implying that the
      demineralization process is more advanced than might be suspected on simple
      clinical examination.

PMID- 15154919
TI  - A multivariate analysis of the outcome of endodontic treatment.
AB  - In the present study, multivariate analyses were performed on clinical and
      treatment variables that may influence the outcome of endodontic treatment. Data
      collected in a previous clinical-radiographic follow-up study were used. Of 810
      treated, 675 roots in 498 teeth were followed for 6 months to 4 yr. Of these, 192
      (the CAP group) had pre-existing, chronic apical periodontitis and 483 (the NAP
      group) had not. Root canal treatment followed a standard procedure with one of
      three sealers chosen at random. Demographic, clinical and radiographic variables
      were recorded at the start of, and during treatment. The periapical index (PAI)
      score was used to record the outcome of treatment, and applied in two different
      endpoint modes (END1 and END2) as the dependent variable for multivariate
      statistical analyses using logistic regression and the general model. The modes
      reflected increasing PAI scores (END1) and conventional success/failure
      assessment (END2). Dropouts were largely similar to the cases followed up. A
      total of 10 preoperative and peroperative variables were found to be
      significantly associated with treatment outcome by the multivariate analyses of
      either the total material or the NAP or CAP subgroups. Several of these were not
      significant in univariate analyses (e.g. the effect of sealer). Conventional
      success/failure analyses (END2) identified fewer of the influential variables and
      had low explanatory power, whereas PAI scores on an ordinal scale (END1) were
      most sensitive in identifying variables of influence on the treatment outcome.

PMID- 15154921
TI  - White spot lesions around brackets: in vitro detection by laser fluorescence.
AB  - Demineralization around orthodontic brackets is one of the side-effects of
      orthodontic treatment. However, simple methods for its early detection,
      quantification and monitoring are lacking. Therefore, the aim of this
      investigation was to evaluate red laser-light induced fluorescence for
      measurement of demineralization around brackets in vitro, and whether an
      interference by the brackets should be expected. The site of measurement was
      standardized on 30 extracted human molars with natural demineralization on smooth
      surfaces. Fluorescence was measured (Diagnodent) on prebonded, etched, bonded
      with stainless steel brackets, and debonded enamel. We found no statistically
      significant difference in fluorescence after etching. After bonding, the
      fluorescence decreased by a median value of 0.5 compared to the prebonded and
      etched enamel. After debonding, the fluorescence increased by a median value of
      0.5 and 1 compared with the prebonded and bonded conditions, respectively. The
      lack of agreement between prebonded and bonded enamel values (limits +12.4/-12.6)
      was possibly due to the difficulty in finding the same spot without the bracket
      (coefficient of repeatability = 9.1-10.8). In vitro, demineralization around
      brackets can be measured by laser fluorescence, but clinical studies are
      necessary.

PMID- 15154922
TI  - Effect of xylitol on mutans streptococci and lactic acid formation in saliva and
      plaque from adolescents and young adults with fixed orthodontic appliances.
AB  - This study aimed to investigate two dose regimens of xylitol-containing tablets
      on the ecology of dental plaque and saliva during treatment with fixed
      orthodontic appliances. The study group comprised 56 healthy patients (mean age
      15.8 yr) randomly assigned into the following groups: A, (n = 23) two xylitol
      tablets two times a day (1.7 g xylitol d(-1)) for 18 wk; B, (n = 23) two tablets
      four times per day (3.4 g xylitol d(-1)) for 18 wk; and C, (n = 10) no tablets.
      The levels of mutans streptococci (ms) were enumerated in plaque and saliva and
      the proportion of xylitol-sensitive (X(S)) strains in saliva was determined by
      autoradiography with [(14)C]-xylitol at baseline and at 6, 12, and 18 wk. The
      lactic acid formation rate was assessed enzymatically in sucrose-challenged
      plaque suspensions. A drop in salivary ms levels was found in Group A after 6 wk
      but not after 12 or 18 wk. The proportion of X(S) ms was decreased after 6 wk in
      groups A and B and remained so during the experimental period. The lactic acid
      formation rates decreased slightly ( approximately 10%) in the two xylitol groups
      compared with baseline. In conclusion, our results showed that although an
      alteration of ms strains was demonstrated following a regular daily low-dose
      intake of xylitol, the long-term total ms counts in plaque and saliva as well as
      plaque acidogenicity remained unchanged.

PMID- 15154923
TI  - Inhibitory effects of cacao bean husk extract on plaque formation in vitro and in
      vivo.
AB  - Cacao bean husk extract (CBH) has been shown to possess antibacterial and
      antiglucosyltransferase activities through its unsaturated fatty acids and
      epicatechin polymers, respectively. In the present study, the antiplaque
      activities of CBH were examined in vitro and in vivo. The extract inhibited the
      adherence of Streptococcus mutans MT8148 to saliva-coated hydroxyapatite and
      reduced the accumulation of artificial dental plaque by S. mutans MT8148 on
      orthodontic wire. The number of mutans streptococci in dental plaque was also
      significantly reduced when human dental plaque was exposed to CBH from 21
      children at 37 degrees C for 1 h. For the in vivo study, 28 volunteers aged 19-29
      yr old rinsed their mouth with CBH, before and after each intake of food and
      before sleeping at night for 4 d without using other oral hygiene procedures.
      Plaque depositions and the numbers of mutans streptococci were reduced in the
      subjects, compared with rinsing with 1% ethanol alone. These results indicate
      that CBH possesses significant antiplaque activity in vitro and in vivo.

PMID- 15154925
TI  - Morphometric analysis of the mandible in growing rats with different masticatory
      functional demands: adaptation to an upper posterior bite block.
AB  - Functional appliances displace the mandible forward and/or downward, causing a
      stretching of the orofacial soft tissues, muscles included. The resulting forces
      are directly or indirectly transmitted to the underlying dento-skeletal tissues.
      The hypothesis underlying the present investigation was that the insertion of a
      bite-opening appliance influences the lateral morphology of the rat mandible
      during growth, and that, moreover, this influence depends on the masticatory
      functional demands. One-hundred and four 4-wk-old male albino rats were divided
      into two groups, fed a hard and soft diet, respectively. After 2 wk, half of the
      animals in each experimental group were fitted with upper posterior blocks, and 4
      wk later they were killed. Their left hemi-mandibles were transilluminated,
      photographed under magnification, and digitized on screen. A total of 170 points
      were used to draw the lateral outline of the mandible. In addition to the
      inhibitory effect on the height of the dento-alveolar process, the upper bite
      block resulted in significant changes in the condyle inclination, the length of
      the coronoid process, and the occlusal plane inclination. Masticatory functional
      demands influenced this adaptation in an additive way. The results raise the
      question of whether orthodontic treatment with posterior bite blocks might have
      different effects on the mandible, depending on the characteristics of the
      orofacial soft tissues.

PMID- 15154924
TI  - Histochemical examination of periodontal junctional epithelium in p21/p27 double
      knockout mice.
AB  - The periodontal junctional epithelium (JE) is maintained in a steady state
      through a dynamic process that balances proliferation and exfoliation of
      epithelial cells. However, mechanisms that regulate JE are not well understood.
      To better understand how proliferation of the JE is controlled in healthy
      gingiva, we have studied functional roles of the CDK (cyclin dependent kinase)
      inhibitors p21 and p27 in JE using knockout mouse model systems. Image analysis
      of the dentogingival junction in p21 or p27 single knockout mice as well as
      p21/p27 double knockout mice (dKO) was performed. The analysis revealed enlarged
      JE in p21/p27 dKO mice due to an increase in the area of the epithelium and
      associated connective tissue 'islands'. Immunohistochemistry was performed for
      p21, p27, cyclin D1, and proliferating cell nuclear antigen (PCNA). The highest
      levels of PCNA-positive cells were detected in the p21/p27 dKO mice, reflecting
      increased cell turnover. Lower levels of cyclin D1 were detected in the JE of
      p21/p27 knockout mice, suggesting that p21 and p27 regulate stability of cyclin
      D1 in oral epithelium. These data suggest that p21 and p27 have a critical role
      in controlling epithelial cell proliferation in the JE and thus function to
      maintain the JE at a normal size.

PMID- 15154926
TI  - Leached components from dental composites and their effects on fertility of
      female mice.
AB  - This study investigated the effects of leached components from a resin-based
      dental composite (Z-100) and bisphenol A (BPA) on female mouse fertility. Leached
      components or BPA (5, 25 and 100 microg kg(-1)) were administered
      intragastrically daily to the test and distilled water to the control groups for
      28 d. Female mice were then mated with sexually mature untreated males and their
      fertility was assessed. The results revealed a significant reduction in the
      number of pregnancies--54.5% vs. 100% (control)--in mice treated with the leached
      components from the dental composite, which also showed an increase of 142% in
      relative ovary weights. Exposure to 25 and 100 microg kg(-1) BPA resulted in
      significant increases in the total number of resorptions out of the total number
      of implantations and significant increases in relative uterine weights. Relative
      ovarian weights were significantly increased at the highest dose. High
      performance liquid chromatography analysis showed that tri-(ethylene glycol)
      dimethacrylate (TEG-DMA) was the major leached component (total: 5945 microg ml(
      1)) from the composite, followed by bisphenol A glycerolate dimethacrylate (BIS
      GMA) (total: 2097 microg ml(-1)) and BPA (total: 78 microg ml(-1)). The results
      suggest that leached components from the dental composite used and commercially
      purchased BPA have adverse effects on the fertility and reproductive system of
      female mice.

PMID- 15154927
TI  - In vitro cell death induced by irradiation and chemicals relevant for dental
      applications; dose-response and potentiation effects.
AB  - Resin-based dental materials polymerized using blue light are frequently used in
      dental practice and may come in contact with the oral mucosa. Remnants from oral
      hygiene product ingredients, such as sodium lauryl sulfate (SLS), add to the
      chemical exposure of the mucosa. The aim of the present in vitro study was to
      elucidate the cytotoxic effects in terms of apoptosis and necrosis after
      exposures to combinations of an adhesive (0.5% and 0.6%), SLS (concentration
      range 0.0025%-0.0075%), and irradiation from a dental curing lamp (radiant
      exposure of 8 J cm(-2)). The test system chosen was rat submandibular salivary
      gland acinar cells, and the cytotoxic effects were measured by fluorescence
      microscopy and flow cytometry methods. Cytotoxicity was observed as a result of
      irradiation. The most pronounced cytotoxic effects were seen in cells exposed to
      a combination of adhesive and SLS compared with those exposed to either agent
      alone. Necrosis was the dominating form of cell death for all exposures, except
      for the highest concentration of SLS. Apoptosis was dose-dependent on SLS in the
      rat submandibular acinar cells. Cytotoxic considerations of dental materials
      should include contributions from irradiation and other chemicals that might be
      present in the oral cavity.

PMID- 15154928
TI  - Color stability of resin matrix restorative materials as a function of the method
      of light activation.
AB  - The purpose was to investigate the influence of curing devices and curing times
      on the yellow value (b-value) of composites, ormocers and compomers after
      performing a suntest (EN ISO 7491). Eight samples of Charisma (CH), Durafill
      (DU), Definite (DE), and Dyract AP (DY) each were light cured with Translux
      Energy (tungsten halogen light) for 20, 40 or 60 s and with Apollo 95-E (plasma
      light) for 3, 10 or 20 s. All samples were subjected to a suntest. Before and
      after the suntest the yellow values (b-values) were determined and the change
      (Delta b) was calculated. When cured with Translux Energy for 20 and 40 s DU, CH,
      and DY revealed significantly negative Delta b-values. The b-value of DE remained
      nearly constant. When cured for 60 s, DU and DE shifted to more yellow while CH
      and DY still bleached a little. When cured with Apollo 95-E, a dramatic bleaching
      process of all materials investigated occurred after the suntest (significant
      negative Delta b). It may be concluded that the bleaching of composites, ormocers
      and compomers depends on (i) the used light curing device and (ii) the chosen
      curing times. The tungsten halogen light provided highly significantly superior
      results.

PMID- 15154929
TI  - Comparison of bonding efficacy of an all-in-one adhesive with a self-etching
      primer system.
AB  - The aim of this study was to compare the bonding efficacy of an all-in-one
      adhesive with that of a self-etching primer system by measuring microleakage
      after thermocycling and the microtensile bond strength (microTBS) to enamel and
      dentin. Circular class V cavities along cement-enamel junctions were prepared in
      20 extracted human premolars. Each 10 teeth were bonded with either AD Bond (AD)
      or Clearfil SE Bond (SE), and filled with a resin composite (Charisma). After
      thermocycling and staining with 0.5% basic fuchsin, the microleakage at the
      coronal and apical walls was evaluated using longitudinal sections. In addition
      20 premolars were used to measure microTBS at 24 h after bonding for these
      adhesives to enamel and dentin that corresponded to the coronal and apical walls
      of the class V cavities. AD showed more microleakage than SE in the coronal
      walls, but there was less microleakage in the apical walls and no difference in
      apical leakage between the two adhesives. microTBS (SD) in MPa to enamel and
      dentin were 25.2 (7.3) and 68.3 (9.4) for AD, and 35.8 (7.4) and 76.4 (7.8) for
      SE, respectively. AD gave a lower microTBS to enamel than did SE. The results
      suggested that the poor adaptation at the coronal wall in AD might be caused by
      the lower bond strength to enamel.

PMID- 15154930
TI  - Effect of acid etching time and technique on interfacial characteristics of the
      adhesive-dentin bond using differential staining.
AB  - Dentin bonding using the total-etch method has been claimed to be technique
      sensitive. The aim of this study is to examine the effect of acid-etch variations
      on the dentin demineralization and interfacial structure of the adhesive-dentin
      bond using a differential staining technique. Single Bond adhesive with 35%
      phosphoric acid gel was used. The occlusal one-third of the crown was removed
      from 60 extracted, unerupted human third molars. Smear layers were created by
      abrading the dentin with 600 grit SiC under water for 30 s. The prepared teeth
      were randomly assigned to four groups according to etching time (Group 1, 10 s;
      Group 2, 15 s; Group 3, 30 s; Group 4, 60 s). In each group, the etching gel was:
      (i) applied and spread to the dentin surface and left to stand undisturbed; (ii)
      applied and gently agitated during etching; (iii) applied without using
      dispensing tips for the syringe and left for the same period as above. After
      rinsing, the etched dentin was then treated with the adhesive per manufacturers'
      instructions. 3-5 micro m thin sections of the adhesive/dentin (a/d) interface
      were cut with a microtome and stained with Goldner's trichrome. Stained, thin
      sections from each prepared tooth were imaged with light microscopy. The depth
      and extent of dentin demineralization, and the a/d interdiffusion zone were
      clearly visible by this differential staining microtechnique. The thickness of
      the interdiffusion zone increased as a function of etching time. However, the
      etchant gel application methods have a significant influence on dentin
      demineralization. Although agitating acid gel facilitates the penetration and
      etching into dentin, it should not be recommended, especially for longer etching
      time. These results indicated that the etching technique has a large effect on
      the profile of both dentin demineralization and interfacial structure.

PMID- 15154931
TI  - A piece of nucleic acid surrounded by controversy: coxsackievirus and the causes
      of Type 1 diabetes.

PMID- 15154932
TI  - Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of
      published case-control studies.
AB  - BACKGROUND: Enteroviruses, in particular Coxsackie B4, have been implicated in
      the aetiology of Type 1 diabetes mellitus, but the epidemiological evidence has
      not been systematically evaluated. METHODS: Systematic review of evidence from
      published controlled studies of the relationship between Coxsackie B virus
      serology and incident or prevalent Type 1 diabetes mellitus. Studies were
      identified through a Medline search (1966 to 2002), supplemented by references
      from identified papers and hand search of relevant journals. All studies (full
      papers, abstracts or letters) with data adequate for calculation of unadjusted
      odds ratios (with 95% confidence intervals) for Type 1 diabetes mellitus in
      relation to Coxsackie B virus serology were included. RESULTS: The review
      included 26 case-control studies; no cohort study met the inclusion criteria.
      Odds ratios for Type 1 diabetes mellitus in serology-positive vs. serology
      negative subjects ranged from 0.2 to 22.3. For Coxsackie B (any serotype) 7/13
      studies had point estimates significantly greater than 1.0 (P < 0.05). For
      Coxsackie B3, Coxsackie B4 and Coxsackie B5-specific assays, 1/11, 6/17 and 1/11
      studies, respectively, had point estimates significantly greater than 1.0.
      Summary odds ratios were not calculated because of doubts about the validity of
      individual study estimates, heterogeneity between studies, and the possibility of
      publication bias. CONCLUSIONS: The results of these studies are inconsistent and
      do not provide convincing evidence for or against an association between
      Coxsackie B virus infection and Type 1 diabetes mellitus. Better designed studies
      using effective assays are needed to resolve this important issue.

PMID- 15154933
TI  - Schizophrenia, the metabolic syndrome and diabetes.
AB  - The prevalence of diabetes is increased in patients with schizophrenia. Although
      many reasons, including hereditary and lifestyle factors, contribute to this
      association, recently there has been heightened interest in the subject because
      of the link between the use of the newer atypical anti-psychotic drugs and the
      development of diabetes. These drugs cause significant weight gain and this may
      be one of the mechanisms by which they increase incident diabetes. The increased
      prevalence of diabetes among people with schizophrenia has implications for the
      delivery of care by psychiatrists, diabetologists and primary care.

PMID- 15154935
TI  - Childhood diabetes: parents' experience of home management and the first year
      following diagnosis.
AB  - AIMS: To explore parents' experience of having a child diagnosed with Type 1
      diabetes, managed at home, and their first year following diagnosis. METHODS: A
      qualitative, longitudinal study based on 40 in-depth interviews with parents of
      20 children with newly diagnosed Type 1 diabetes managed at home from diagnosis
      in South Wales. RESULTS: Many parents were alarmed by the speed of diagnosis
      following the gradual progress of their child's symptoms. The provision of
      timely, adequate information was important to all parents. Although five parents
      had initial concerns about going home, all parents were subsequently pleased
      their children had not been hospitalized. Home management enabled parents to
      integrate diabetes management into the family's normal lifestyle from diagnosis.
      Professional support, particularly accessible telephone advice, was valued by and
      reassured parents. Parents experienced a loss of spontaneity, a continuing fear
      of hypoglycaemia and did not want their child to feel different to other
      children. Acutely aware of the seriousness of diabetes, they did their utmost to
      achieve optimal glycaemic control but felt that diabetes could not 'dominate' if
      they were to lead a 'normal' life. CONCLUSIONS: The experience of parents in this
      study suggests that parents of children with newly diagnosed diabetes are able to
      cope successfully when given the opportunity to start treatment at home.
      Therefore, if children with diabetes are clinically well at diagnosis, this study
      supports home management as a system of care from the parents' point of view.
      These findings are relevant to clinicians, policy makers and health service
      managers involved in planning and providing paediatric diabetes care.

PMID- 15154934
TI  - Left ventricular dysfunction in normotensive Type 1 diabetic patients: the impact
      of autonomic neuropathy.
AB  - AIMS: The pathophysiological mechanisms responsible for increased cardiovascular
      mortality in diabetic autonomic neuropathy (AN) are largely unknown. The aim was
      to determine the relative role of AN in the pathogenesis of cardiac diastolic
      dysfunction and left ventricular hypertrophy in Type 1 diabetes. METHODS: Ten
      Type 1 diabetic patients with AN, defined by cardiovascular tests (AN+) and 10
      age- and sex-matched patients without neuropathy (AN-) as well as 10 healthy
      subjects (C) participated in the study. Left ventricular diastolic function was
      assessed by Doppler echocardiography, whilst systolic function was evaluated by
      cine magnetic resonance (MR) imaging. RESULTS: Doppler echocardiography showed a
      significant decrease in E/A ratio, i.e. the ratio between peak Early transmitral
      filling velocity during early diastole (E-wave) and peak transmitral Atrial
      filling velocity during late diastole (A-wave), in AN+ compared with C (P < 0.01)
      [0.95 +/- 0.08 (mean +/- sem) (AN+); 1.19 +/- 0.09 (AN-); 1.33 +/- 0.10 (C)]. The
      E-wave deceleration time was significantly shorter in AN+ compared with AN- and C
      (P < 0.02) [178 +/- 7 ms (AN+); 203 +/- 9 ms (AN-); 205 +/- 9 ms (C)]. Cine MR
      imaging showed a significantly greater left ventricular mass index in AN+
      compared with C [103 +/- 4 g/m(2) (AN+) vs. 98 +/- 7 (AN-) and 92 +/- 4 g/m(2)
      (C), P < 0.05]. CONCLUSION: Autonomic neuropathy is associated with left
      ventricular hypertrophy and diastolic dysfunction in Type 1 diabetic patients.

PMID- 15154936
TI  - Decreased stiffness at the ankle joint in patients with long-term Type 1
      diabetes.
AB  - AIMS: To evaluate contractile and reflex properties of the soleus muscle together
      with ankle joint stiffness in long-term Type 1 patients. METHODS: Stretch reflex
      and muscle function of the soleus muscle was tested in 15 Type 1 diabetes
      mellitus patients and 15 controls. M-wave amplitude and maximal twitch torque was
      elicited by supramaximal stimulation of the tibial nerve. The stretch reflex was
      elicited by a 4 degree rotation of the ankle. RESULTS: Rise time and fall time of
      the maximal twitch torque were increased compared with controls. The amplitude of
      the short latency stretch reflex was significantly reduced in patients at
      contraction levels of 5-30 Nm. At a contraction level of 5 Nm the median stretch
      reflex threshold was 10 degrees/s in patients and 6 degrees/s in controls (P =
      0.03). Stiffness was decreased in diabetic patients, especially at lower
      contraction levels. There was no significant correlation between the clinical
      neuropathy score and stiffness. In contrast, high neuropathy score was correlated
      with low amplitude of the reflex amplitude (rho = -0.51, P = 0.05). CONCLUSIONS:
      We demonstrate altered contractile properties, a decrease in stretch reflex of
      the soleus muscle, and a reduced stiffness at the ankle joint in patients with
      long-term Type 1 diabetes. These changes may cause delayed muscle contraction and
      impaired reflex modulation which could contribute to gait disturbances and
      increased number of falls in diabetic patients.

PMID- 15154937
TI  - Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in
      Type 2 diabetes mellitus.
AB  - AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the
      pathogenesis of diabetes mellitus. We determined whether alterations of plasma
      and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic
      patients. METHODS: One hundred and seven patients and 47 healthy controls were
      studied. Study subjects were divided into four groups using urinary albumin-to
      creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a
      normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n =
      37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured
      by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations
      were significantly higher in the diabetic groups, even at the normoalbuminuric
      stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P
      = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced.
      (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients
      than in the normotensive individuals with diabetes. (iii) In those with diabetes,
      plasma VEGF levels were found to be positively correlated with plasma urea (r =
      0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be
      positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r
      = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = 
      0.557, P < 0.001). Urinary VEGF and serum creatinine were independently
      correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased
      during the earlier stage of diabetic nephropathy and was significantly correlated
      with urinary albumin excretion. This suggests that urinary VEGF might be used as
      a sensitive marker of diabetic nephropathy and for predicting disease
      progression.

PMID- 15154938
TI  - Vascular endothelium and inflammatory process, in patients with combined Type 2
      diabetes mellitus and coronary atherosclerosis: the effects of vitamin C.
AB  - AIMS: Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both
      associated with endothelial dysfunction and elevated oxidative and inflammatory
      state. We examined the effect of vitamin C on endothelial function and levels of
      soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and
      tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non
      diabetic subjects. METHODS: Thirty-seven patients with DM + CAD, 17 patients with
      DM without CAD and 21 non-diabetic subjects were divided into groups receiving
      vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was
      determined using venous occlusion gauge-strain plethysmography. Forearm
      vasodilatory response to reactive hyperemia was considered as index of
      endothelium-dependent dilation. RESULTS: Baseline levels of IL-6 and TNF-alpha
      were significantly higher in patients with DM + CAD compared with patients with
      DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were
      also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels
      were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P <
      0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM +
      CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive
      hyperaemia only in the DM + CAD group, while it had no effect on serum levels of
      sVCAM-1, TNF-alpha and IL-6 in any of the groups. CONCLUSIONS: Type 2 diabetes
      mellitus is associated with impaired endothelial function and increased levels of
      TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C
      significantly increased forearm vasodilatory response to reactive hyperaemia only
      in patients with combined DM and CAD.

PMID- 15154939
TI  - Development and progression of diabetic retinopathy in patients with Type 1
      diabetes who are positive for GAD autoantibody.
AB  - AIMS: To investigate the relationship between autoantibodies to glutamic acid
      decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the
      role of autoimmunity in retinopathy. METHODS: Patients with Type 1 diabetes for
      more than 10 years who had been diagnosed under age 30 (13-28 years) were
      studied. They were classified into three groups. The PDR group consisted of 22
      patients, the pre-PDR group was 26 patients, while the non-DR group was 32
      patients who had Type 1 diabetes without retinopathy. Blood was collected to
      measure autoantibodies to GAD, and the relationship between PDR and GAD
      positivity was investigated in a cross-sectional study. RESULTS: The highest
      positivity rate of GAD autoantibodies was 50.0% in the non-DR group, followed by
      the pre-PDR group (30.8%) and the PDR group (18.2%). CONCLUSIONS: Production or
      existence of GAD autoantibodies may contribute to the prevention of retinopathy.

PMID- 15154940
TI  - The value of the Rydel-Seiffer tuning fork as a predictor of diabetic
      polyneuropathy compared with a neurothesiometer.
AB  - AIMS: The aim of the study was to investigate the predictive value of the Rydel
      Seiffer tuning fork for detecting diabetic neuropathy and to compare it with an
      electronic neurothesiometer. METHODS: In 2022 consecutive diabetic subjects,
      peripheral polyneuropathy was diagnosed by vibration perception threshold (VPT)
      at the tip of both great toes using a 128-Hz tuning fork and a neurothesiometer,
      by simple bedside tests and by the presence of neuropathic symptoms. These
      evaluations were further combined to diagnose peripheral nerve dysfunction
      (abnormal bedside tests) and symptomatic neuropathy. VPT was also measured in 175
      non-diabetic control subjects to define normal values. RESULTS: VPT was normal in
      1917 subjects and abnormal in 105 (5.2%) patients when measured by the tuning
      fork. Patients with an abnormal vibration test were significantly (P < 0.0001)
      older than subjects with a normal vibration sense, while diabetes duration and
      HbA(1c) of the former were also significantly elevated. The same was true for the
      percentages of an abnormal 10-g monofilament test (66.7% vs. 7.2%, P < 0.0001)
      and a missing Achilles' tendon reflex (68.6% vs. 24.8%, P < 0.0001). Finally, the
      VPT measured by the neurothesiometer was 2.5 times higher in patients with an
      abnormal tuning fork test (32.0 +/- 9.8 vs. 12.5 +/- 6.4 V, P < 0.0001). The plot
      of the difference of both methods against their mean yielded a good agreement of
      the two VPT measurements, and the tuning fork had a high sensitivity and positive
      predictive value for the diagnosis of abnormal bedside tests and for symptomatic
      neuropathy. CONCLUSION: The tuning fork reliably detected peripheral neuropathy
      in comparison with the neurothesiometer. A tuning fork is a useful screening test
      for diabetic neuropathy.

PMID- 15154941
TI  - An increase in insulin sensitivity and basal beta-cell function in diabetic
      subjects treated with pioglitazone in a placebo-controlled randomized study.
AB  - AIMS: To investigate the effect of treatment with pioglitazone on beta-cell
      function and insulin sensitivity in Type 2 diabetes. METHODS: Thirty subjects
      with diet-controlled Type 2 diabetes were randomized to 3 months treatment with
      pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling
      for homeostatic model assessment (HOMA), followed by an intravenous glucose
      tolerance test and hyperglycaemic clamp, followed by an euglycaemic
      hyperinsulinaemic clamp; at baseline and after treatment. RESULTS: All results
      are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by
      24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated
      insulin sensitivity, M/I, increased in the pioglitazone group compared with
      placebo: +15.1 (2.8) l kg(-1) min(-1) vs. +3.2 (2.9) l kg(-1) min(-1),
      respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml
      compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B
      increased with pioglitazone, +11.5% (4.8) vs. -2.0% (4.8) with placebo (P =
      0.049), but there was no change in stimulated beta-cell function as determined by
      hyperglycaemic clamps. There was a significant reduction in the
      proinsulin/insulin ratio in the pioglitazone group, -0.057 (0.02) compared with
      placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA(1c)
      of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There
      was no significant weight gain associated with pioglitazone therapy: +0.7 (sem
      0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). CONCLUSIONS: Basal beta
      cell function and insulin sensitivity improved following pioglitazone therapy.
      The improvement in proinsulin to insulin ratio suggests that beta-cells are under
      less stress.

PMID- 15154942
TI  - Effects of diabetes on plasma nitrotyrosine levels.
AB  - BACKGROUND: Oxidative stress plays a major role in disease processes such as
      atherosclerosis and diabetes. Peroxynitrite is a reaction product of nitric oxide
      (NO) and superoxide and a potent oxidant. The peroxynitrite-mediated tyrosine
      nitration, which forms nitrotyrosine (NT), is associated with several
      pathological conditions. METHODS: We measured plasma NT levels using the HPLC
      method in 40 Mexican Americans with diabetes, but not taking medications, and 40
      age- and sex-matched euglycaemic controls. RESULTS: Plasma-free NT levels were
      not different between subjects with diabetes (11.0 +/- 1.7 nmol/l, n = 40) and
      with non-diabetes (10.4 +/- 1.5 nmol/l, n = 40). There was also no association
      with levels of fasting glucose (r = -0.049, P = 0.663) or 2-h glucose (r = 
      0.099, P = 0.390). However, females had significantly lower free NT level (7.6 +/
      1.4 nmol/l, n = 40) than males (13.8 +/- 1.7 nmol/l, n = 40, P = 0.005), which
      were not affected by age, smoking status, BMI and glucose levels. CONCLUSIONS: In
      contrast to some earlier reports, our study shows that diabetes has no effect on
      plasma NT levels in Mexican Americans. We have also demonstrated lower free NT
      levels in females than males, which may partly explain the lower risk profile to
      vascular disease in women.

PMID- 15154943
TI  - Strong association of C-reactive protein with body mass index and 2-h post
      challenge glucose in non-diabetic, non-smoker subjects without hypertension.
AB  - AIMS: Increases in C-reactive protein (CRP) levels have been shown to be
      associated with cardiovascular diseases as well as asymptomatic atherosclerosis
      and to be closely related to traditional cardiovascular risk factors. The aim of
      this study was to determine the clinical and biochemical characteristics
      associated with CRP in non-diabetic, non-smoker subjects without hypertension.
      METHODS: A 75-g oral glucose tolerance test was performed on 305 Japanese
      subjects aged 40-70 years who were undergoing health examinations. We recruited
      non-diabetic, non-smoker subjects without hypertension. Subjects with known
      cardiovascular diseases, chronic or acute inflammation, malignant diseases, or
      autoimmune disorders were excluded. Plasma high-sensitivity CRP was measured in
      125 subjects who satisfied the admission criteria. RESULTS: Plasma CRP levels
      were significantly higher in the 28 subjects with impaired glucose tolerance
      (IGT) than that in the 97 subjects with normal glucose tolerance (NGT) (median
      0.53, range 0.18-1.10 mg/l vs. median 0.32, range 0.17-0.49 mg/l; P = 0.032).
      There was a positive correlation of CRP with body mass index (BMI),
      triglycerides, uric acid, fasting glucose, oral glucose tolerance test (OGTT) 1-h
      glucose, OGTT 2-h glucose, and a negative correlation with HDL cholesterol.
      Multivariate regression analysis identified BMI (F = 8.57, P = 0.004) and OGTT 2
      h glucose (F = 5.96, P = 0.016) as independent predictors for CRP. CONCLUSIONS:
      BMI and OGTT 2-h glucose are the most important predictors for plasma CRP in non
      diabetic, non-smoker subjects without hypertension.

PMID- 15154944
TI  - Patients and nurses determine variation in adherence to guidelines at Dutch
      hospitals more than internists or settings.
AB  - AIMS: To measure adherence to recently developed diabetes guidelines at Dutch
      hospital outpatient clinics and distinguish determinants for variations in care
      on hospital, internist and patient levels. METHODS: Thirteen general hospitals
      with 58 internists recruited 1950 diabetic patients. Data were extracted from
      medical files (n = 1915) and from patient questionnaires (n = 1465). Multilevel
      logistic regression analysis was performed to explain differences in adherence
      rates to the guidelines. RESULTS: Adherence to process measures was high, except
      for the examination of feet, calculation of the body mass index and patient
      education activities (the mean of 12 process measures was 64%). Adherence to
      intermediate outcome indicators was moderate. The mean percentage of patients
      with HbA(1c) < 7.0% was 23%. Adherence variation on a hospital level was very
      small (0.6-7.9%), on an internist level moderate (0.4-18.8%) and on a patient
      level high (74.4-98.8%). Adherence to all process measures and most of the
      intermediate outcome indicators was highest in the patients seen by a diabetes
      specialist nurse. DISCUSSION: More focus on patient involvement in diabetic care
      and the contribution of diabetes specialist nurses may be important factors in
      improving the quality of diabetes care.

PMID- 15154945
TI  - Improving glycaemic control of patients with Type 2 diabetes in a primary care
      setting: a French application of the Staged Diabetes Management programme.
AB  - AIMS: To assess the impact of a French adaptation of the Staged Diabetes
      Management (SDM) programme on glycaemic control of people with Type 2 diabetes in
      primary care. Secondary endpoints were blood pressure, blood lipids, healthcare
      costs and quality of life. METHODS: Prospective, randomized controlled study, of
      1 years' duration. General practitioners (GPs) were recruited in four separate
      districts of a French region. They enrolled consecutive patients with Type 2
      diabetes. GPs in the intervention group were educated in the SDM programme. GPs
      in the control group were asked to provide usual care. Healthcare costs were
      collected by medical departments of the Health Insurance systems. Quality of life
      was assessed with the Duke Health Profile. RESULTS: Three hundred and forty
      patients enrolled by 57 GPs completed the study, 192 in the intervention group
      and 148 in the control group. Patients in the intervention group were managed
      more adequately in accordance with the guidelines (P < 0.05 for nine out of 10
      items). HbA(1c) decreased by 0.31% in the intervention group and increased by
      0.56% in the control group, resulting in a difference of 0.87% by the end of the
      study (P = 0.001). Blood pressure and blood lipids did not differ between groups.
      Occurrence of major complications was low and identical in both groups.
      Incremental costs during the study in the intervention group were 35 euros per
      patient per month, and this was not significantly different in comparison with
      the control group. Quality of life was not affected by the intervention.
      CONCLUSIONS: Educating GPs in the French adaptation of the SDM programme improves
      glycaemic control in a primary care setting, without significantly increasing
      healthcare costs.

PMID- 15154946
TI  - Educational outreach in diabetes to encourage practice nurses to use primary care
      hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled
      trial.
AB  - OBJECTIVE: To determine the effectiveness of specialist nurse delivered education
      in primary care to improve control of hypertension and hyperlipidaemia in
      patients with diabetes. DESIGN AND SETTING: Practice-level randomized controlled
      trial, Salford, England. SUBJECTS: From 44 practices, 10 303 subjects presenting
      in general practice with raised blood pressure (= 140/80 mmHg), raised total
      cholesterol (= 5.0 mmol/l) or both. INTERVENTIONS: Practices were randomized to
      receive either the intervention for hyperlipidaemia or for hypertension;
      practices acted as control for the intervention not received. Specialist nurses
      arranged a schedule of visits with general practitioners and general practice
      nurses, reminding them of diabetes protocols and clinical targets. They provided
      educational materials and protocols used in secondary care for nurse and doctor
      interventions including stepping up pharmacotherapy when necessary. Practices
      received a list of patients in their practice who were poorly controlled at their
      last annual review; new and recalled patients were targeted. OUTCOME MEASURES: At
      subsequent annual review, blood pressure and total cholesterol values were
      obtained from the Salford electronic diabetes register for patients from
      participating practices. RESULTS: Overall, specialist nurse-led educational
      outreach to primary care was associated with no improvement in patients achieving
      target after 1 year-odds ratio (OR): 1.03 (95% CI 0.95-1.11; P = 0.52). Similar
      results were achieved with hyperlipidaemia OR: 1.04 (95% CI 0.88-1.23; P = 0.62)
      and hypertension OR: 1.01 (95% CI 0.80-1.27; P = 0.93). CONCLUSION: This study
      provides evidence that the use of specialist nurses to perform educational
      outreach to improve target adherence to patients with diabetes in primary care is
      not effective.

PMID- 15154947
TI  - An assessment of the adequacy of suspension of insulin in pen injectors.
AB  - AIMS: To evaluate the completeness of insulin resuspension by users of neutral
      Hagedorn (NPH) insulin pens and premixed insulin pens and to relate this to how
      patients mix insulin before injecting. METHODS: Patients (n = 180) administering
      a medium duration or premixed insulin in cartridges in disposable pens were asked
      questions about mixing insulin, injection technique and storing insulin. They
      were also asked to demonstrate how they mixed their insulin and to send in a half
      used pen. The cloudy component equates to the complexed insulin, while the clear
      component is the diluting fluid or soluble insulin, depending on the type of
      insulin used. The optical density, a simple way of measuring cloudiness, was
      measured in each cartridge or disposable pen and was compared with the range
      obtained from a series of unused control pens. The results for 146 pens
      containing the most commonly used insulin were included. The 21 patients whose
      residual pen insulins showed optical densities > 5 SD from the mean were re
      interviewed and their medical records were examined in detail. Insulin in the
      pens was also measured by immunoassay to confirm the utility of optical density
      measurements. RESULTS: Only one patient mixed the insulin as the manufacturers
      recommended. In 58 out of 146 pens or cartridges (40%) the opacity of the insulin
      varied significantly from the expected value. CONCLUSIONS: Most patients in
      Kirkcaldy do not mix insulin adequately. This may result in their giving
      different incorrect doses of insulin during the use of each pen. More emphasis
      should be given to teaching patients to mix correctly.

PMID- 15154948
TI  - Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta
      analysis.
AB  - AIM: The association of diabetes mellitus with primary open-angle glaucoma has
      been controversial. The study aimed to examine the strength of this association
      through a detailed meta-analysis of studies published in peer-reviewed journals.
      METHODS: A comprehensive search for articles published through 2002 was performed
      and data were abstracted. Prior to meta-analysis, all studies were evaluated for
      publication bias and heterogeneity. Pooled odds ratio (OR) was calculated using
      the random and the fixed-effects model. RESULTS: Twelve studies published between
      1987 and 2001 were included (five case-control studies and seven cross-sectional
      studies). Significant heterogeneity among the studies was detected (P = 0.023).
      No evidence of publication bias was found (P = 0.37). The association of diabetes
      mellitus with primary open-angle glaucoma was statistically significant assuming
      either a random effects [OR = 1.50, 95% confidence interval (CI) 1.16, 1.93], or
      a fixed-effects model (OR = 1.27, 95% CI 1.10, 1.45). CONCLUSIONS: Our meta
      analysis results suggest that diabetic patients are at significantly increased
      risk of developing primary open-angle glaucoma. Clinicians should be aware of
      this possibility.

PMID- 15154949
TI  - Increased levels of triglycerides, BMI and blood pressure and low physical
      activity increase the risk of diabetes in Swedish women. A prospective 18-year
      follow-up of the BEDA study.
AB  - AIM: To investigate risk factors for the development of diabetes in middle-aged
      women. METHODS: A random population sample of 1351 women without prior diabetes
      or cardiovascular disease, aged 39-65 years, took part in a screening study in
      1979-1981 with questionnaires, physical examination and blood sampling.
      Development of diabetes up to 1998 was identified at a second examination in 1997
      1998. RESULTS: Seventy-three women (5.4%) were diagnosed with diabetes during
      follow-up. As expected, obesity resulted in a rising age-adjusted risk with
      hazards ratio 3.2 [95% confidence interval (CI) 1.3, 8.1] at body mass index
      (BMI) 24-27 kg/m(2), and 8.3 (3.5, 19.7), at BMI > or = 27, compared with BMI <
      22 kg/m(2). S-triglycerides (TG) carried a steeply increasing age-adjusted risk
      with hazards ratio 4.0 (95% CI 2.1, 7.6) already at s-TG 1.0-1.4 mmol/l, 7.1
      (3.6, 14.0) at s-TG 1.5-1.9 mmol/l and 9.3 (4.3, 20.2) at s-TG > or = 2.0 mmol/l
      compared with s-TG < 1.0 mmol/l. Increasing systolic blood pressure (SBP) to 130
      144, 145-159 and > or = 160 mmHg escalated the hazards ratio of diabetes to 1.6
      (0.8, 3.3), 3.6 (1.7, 7.4) and 5.6 (2.7, 11.4), respectively, compared with SBP <
      130 mmHg. Also, low physical activity predicted diabetes, with hazards ratio 2.1
      (1.3, 3.3) for sedentary compared with non-sedentary activity. Smoking was not
      associated with increased risk of diabetes. After adjustment for BMI, SBP and
      physical activity, increasing TG level remained a strong and significant risk
      factor for diabetes [hazards ratio 3.0 (1.6, 5.7), 3.7 (1.8, 7.7) and 4.5 (2.0,
      10.0), P < 0.001]. CONCLUSIONS: Among middle-aged Swedish women even very
      slightly elevated s-TG resulted in a considerably enhanced risk of developing
      diabetes, which was independent of age, BMI, blood pressure and physical
      activity.

PMID- 15154951
TI  - The advantages and disadvantages of a 'herbal' medicine in a patient with
      diabetes mellitus: a case report.
AB  - BACKGROUND: Patient-initiated alternative treatments in the management of chronic
      conditions are common and increasing in the United Kingdom. To date, there have
      been no reports of herbal medicine use alone in the management of diabetes
      mellitus. We report here the case of a man who attained excellent glycaemic
      control using a 'herbal' medicine and reveal how important it was to identify the
      products of active constituents. CASE REPORT: A 48-year-old man attending our
      clinic in Tooting, South London with known Type 2 diabetes, with evidence of both
      micro- and macro-vascular diabetes-related complications, was poorly controlled
      despite a drug regimen consisting of oral metformin and twice daily insulin. He
      went to India for at least 1 year and on returning to the clinic had excellent
      glycaemic control off all diabetic medication. While away he had started himself
      on a regimen of three different 'herbal' balls. Samples of blood were found to
      contain chlorpropamide in a therapeutic concentration; chlorpropamide was also
      found in one of the balls. He has been counselled on the potential risks
      associated with chlorpropamide and his treatment reverted to a more conventional
      treatment regimen. CONCLUSIONS: General practitioners and hospital physicians
      should be alert to those patients returning from abroad on effective 'herbal'
      medications that these may in fact contain an active ingredient.

PMID- 15154950
TI  - Acute brain injury in hypoglycaemia-induced hemiplegia.
AB  - BACKGROUND: The development of hemiplegia as a result of hypoglycaemia was first
      described in 1928. However, the mechanism remains unclear. CASE REPORT: We report
      a case of a 58-year-old male with diabetes, who developed left hemiplegia during
      a severe hypoglycaemic event. Results Diffusion-weighted magnetic resonance
      imaging detected an increased signal intensity in the pons, indicating that the
      patient's hemiplegia resulted from acute brain injury. CONCLUSIONS: This report
      provides evidence that acute brain injury may be a cause of the neurological
      deficit.

PMID- 15154952
TI  - Familial hyperinsulinaemia associated with epilepsy and mental retardation--a
      syndrome of familial insulin resistance.
AB  - BACKGROUND: Variants of type A insulin resistance, characterized by female
      hyperandrogenism and 'acromegaloid' features, have been ascribed to genetic
      defects of the insulin receptor or post-receptor pathways via autosomal dominant
      or recessive inheritance patterns. Whilst a variety of congenital syndromes of
      insulin resistance are identified by their characteristic clinical phenotypes, an
      association with epilepsy and mental retardation has not previously been
      reported. CASE REPORT: We describe three female siblings (aged 12, 19 and 21)
      with fasting hyperinsulinaemia (116-443 pmol/l; normal range < 80 pmol/l) and
      mental retardation. Two siblings also have epilepsy. The eldest has features of
      severe insulin resistance with dyslipidaemia, acanthosis nigricans, 'acromegaloid
      features' and diabetes requiring high dose insulin therapy in combination with a
      glitazone. Their mother has fasting hyperinsulinaemia (113 pmol/l), mental
      retardation and epilepsy. None had clinical or biochemical features of
      hyperandrogenism or evidence of pigmentory retinopathy, deafness or renal
      insufficiency. Autoantibody screens were negative. Interestingly, there is no
      evidence of mental retardation or epilepsy among males in the family. CONCLUSION:
      This family suggests the presence of a yet-undefined syndrome of familial insulin
      resistance affecting female kindred. Further studies are being undertaken to
      clarify the genetic defects and mode of inheritance.

PMID- 15154953
TI  - Evaluation of a local optometric diabetic retinopathy screening service.
AB  - AIMS: To determine the sensitivity and specificity for sight-threatening eye
      disease (STED) of the diabetic retinopathy screening scheme for Stockport during
      the period 1 April 2000 to 31 March 2001. METHODS: A random sample of screen
      negative patients was recalled for further assessment by consultant
      ophthalmologists. Screen-positive patients, who were referred, were tracked
      through the hospital system to determine the outcome. RESULTS: In a 12-month
      period, 3510 individuals with diabetes were screened, which is 1.2% of the
      district population. Sensitivity for STED was 75.8%[95% confidence interval (CI)
      49.3, 99.99] and specificity for STED was 99.0% (95% CI 98.6, 99.3). CONCLUSIONS:
      The current screening arrangements in Stockport are satisfactory in terms of
      sensitivity and specificity. Population coverage was 1.2% over 12 months and 1.5%
      over 15 months and needs to be improved. An integrated computerized register
      requires further development.

PMID- 15154954
TI  - Post-challenge hyperglycaemia is an independent risk factor for arterial
      stiffness in Japanese men.
AB  - AIMS: Arterial stiffness is an independent predictor of cardiovascular disease,
      but the impact of post-challenge hyperglycaemia on arterial stiffness is unknown.
      To investigate the association between arterial stiffness and post-challenge
      hyperglycaemia, we measured the second derivative of photoplethysmogram as an
      indicator of arterial stiffness. METHODS: This study was done in 159 asymptomatic
      Japanese men aged 50.7 +/- 13.0 years. All subjects underwent a 75-g oral glucose
      tolerance test and measurement of the second derivative of photoplethysmogram.
      RESULTS: According to the World Health Organization criteria (1998), 110 subjects
      had normal glucose tolerance, 10 had impaired fasting glucose, 30 had impaired
      glucose tolerance, and nine had diabetes. The b/a ratio (an index of arterial
      stiffness) showed a significant relationship with age (r = 0.58, P < 0.0001),
      height (r = -0.33, P < 0.0001), 2-h post-challenge glucose (r = 0.32, P <
      0.0001), systolic blood pressure (r = 0.22, P = 0.006), and diastolic blood
      pressure (r = 0.21, P = 0.009). After adjustment for age and height, there were
      significant correlations between the b/a ratio and diastolic blood pressure (r =
      0.18, P = 0.02), fasting glucose (r = 0.16, P = 0.049), and 2-h post-challenge
      glucose (r = 0.21, P = 0.009). Stepwise multiple regression analysis showed that
      only age (beta= 0.006, SE = 0.0007, P < 0.001) and 2-h post-challenge glucose
      (beta = 0.0005, SE = 0.0002, P < 0.05) contributed significantly to the b/a ratio
      (adjusted R(2) = 0.38). CONCLUSIONS: These results indicate that post-challenge
      hyperglycaemia is an independent risk factor for arterial stiffness.

PMID- 15154955
TI  - Changes in prevalence and site of care of diabetes in a health district 1991
      2001.
AB  - AIMS: Alongside a rising prevalence of known diabetes, patterns of care for
      diabetes have been changing in the United Kingdom. The aim of this study is to
      describe the changes in the prevalence of known diabetes and shift in site of
      care of patients in a single health district over a 10-year period. METHODS:
      Repeat cross-sectional study over 10 years of patients with diabetes resident in
      North Tyneside district. RESULTS: The crude prevalence of known diabetes in North
      Tyneside rose from 1.1 to 3.0% between 1991 and 2001. The proportion of patients
      receiving their diabetes care wholly in primary care rose significantly from
      608/2236 (27%) in 1991 to 3995/5809 (69%) in 2001 (chi(2) = 968, 1 d.f., P <
      0.001). The number of patients attending secondary care also rose by 14% over
      this period of time from 1508 to 1712 patients. CONCLUSIONS: Most of the extra
      workload of the rising prevalence of diabetes has been met in primary care.
      However, hospital care has not seen a drop in workload. This has important
      implications for health care planning, as an increase in resources will be
      required within both primary and secondary care to meet the needs of the diabetic
      population.

PMID- 15154956
TI  - ROMEO: rethink organization to improve education and outcomes.
AB  - AIMS: Scarcity of resources, expertise and evidence-based models have so far
      limited delivery of patient-centred diabetes education. We have developed and
      validated a group care approach that is applicable to everyday clinical practice
      and cost-effective in improving metabolic control, knowledge of diabetes, health
      behaviours, and quality of life in Type 2 diabetes. A clinical trial (ROMEO) was
      planned to evaluate applicability and reproducibility of group care in other
      outpatients facilities and assess its impact on a larger patient population.
      METHODS: Multicentre, randomized, controlled clinical trial of group vs.
      individual care in the routine management of Type 2 diabetes. Nine hundred
      patient aged < 80, with diabetes of > or =1 year known duration, treated by
      either diet alone or diet and oral agents, will be recruited in 15 centres and
      followed for 4 years. Training of physicians, nurses and dietitians included
      preparation of operating manual and videos, interactive sessions, and evaluation
      of local facilities and resources. RESULTS:  PRIMARY MEASUREMENTS: 3-monthly
      HbA1c, fasting blood glucose, body weight, waist-hip ratio, yearly blood lipids,
      and bi-yearly assessment of knowledge of diabetes, health behaviours and quality
      of life. SECONDARY OUTCOMES: systolic and diastolic blood pressure, evaluation of
      ECG for ischaemia and QT interval, hypoglycaemic and anti-hypertensive medication
      and cardiovascular events. Analysis will be by intention-to-treat. DISCUSSION: If
      ROMEO confirms that group care can be successfully implemented in different
      clinics, a novel clinico-pedagogic tool will have been acquired to support
      patient-centred education, improve lifestyle and outcomes, support team work,
      enhance providers' attitudes and competencies and ameliorate diabetes care
      organization.

PMID- 15154957
TI  - Effectiveness of a new brand of stock 'diabetic' shoes to protect against
      diabetic foot ulcer relapse. A prospective cohort study.

PMID- 15154958
TI  - Access to dietetic services in the UK.

PMID- 15154960
TI  - Fasting plasma glucose values alone miss most abnormalities of glucose tolerance
      in the postpartum.

PMID- 15154962
TI  - Preventing Type 2 diabetes: an evolutionary view.

PMID- 15154964
TI  - Screening for diabetic retinopathy--false positives do occur (it could be
      Shagreene).

PMID- 15154966
TI  - Feature selection for splice site prediction: a new method using EDA-based
      feature ranking.
AB  - BACKGROUND: The identification of relevant biological features in large and
      complex datasets is an important step towards gaining insight in the processes
      underlying the data. Other advantages of feature selection include the ability of
      the classification system to attain good or even better solutions using a
      restricted subset of features, and a faster classification. Thus, robust methods
      for fast feature selection are of key importance in extracting knowledge from
      complex biological data. RESULTS: In this paper we present a novel method for
      feature subset selection applied to splice site prediction, based on estimation
      of distribution algorithms, a more general framework of genetic algorithms. From
      the estimated distribution of the algorithm, a feature ranking is derived.
      Afterwards this ranking is used to iteratively discard features. We apply this
      technique to the problem of splice site prediction, and show how it can be used
      to gain insight into the underlying biological process of splicing. CONCLUSION:
      We show that this technique proves to be more robust than the traditional use of
      estimation of distribution algorithms for feature selection: instead of returning
      a single best subset of features (as they normally do) this method provides a
      dynamical view of the feature selection process, like the traditional sequential
      wrapper methods. However, the method is faster than the traditional techniques,
      and scales better to datasets described by a large number of features.

PMID- 15154967
TI  - CD8+ T lymphocyte responses target functionally important regions of Protease and
      Integrase in HIV-1 infected subjects.
AB  - BACKGROUND: CD8+ T cell responses are known to be important to the control of HIV
      1 infection. While responses to reverse transcriptase and most structural and
      accessory proteins have been extensively studied, CD8 T cell responses
      specifically directed to the HIV-1 enzymes Protease and Integrase have not been
      well characterized, and few epitopes have been described in detail. METHODS: We
      assessed comprehensively the CD8 T cell responses to synthetic peptides spanning
      Protease and Integrase in 56 HIV-1 infected subjects with acute, chronic, or
      controlled infection using IFN-gamma-Elispot assays and intracellular cytokine
      staining. Fine-characterization of novel CTL epitopes was performed on peptide
      specific CTL lines in Elispot and 51Chromium-release assays. RESULTS: Thirteen
      (23%) and 38 (68%) of the 56 subjects had detectable responses to Protease and
      Integrase, respectively, and together these targeted most regions within both
      proteins. Sequence variability analysis confirmed that responses cluster largely
      around conserved regions of Integrase, but responses against a large, highly
      conserved region of the N-terminal DNA-binding domain of Integrase were not
      readily detected. CD8 T cell responses targeted regions of Protease that contain
      known Protease inhibitor mutation residues, but strong Protease-specific CD8 T
      cell responses were rare. Fine-mapping of targeted epitopes allowed the
      identification of three novel, HLA class I-restricted, frequently-targeted
      optimal epitopes. There were no significant correlations between CD8 T cell
      responses to Protease and Integrase and clinical disease category in the study
      subjects, nor was there a correlation with viral load. CONCLUSIONS: These
      findings confirm that CD8 T cell responses directed against HIV-1 include
      potentially important functional regions of Protease and Integrase, and that
      pharmacologic targeting of these enzymes will place them under both drug and
      immune selection pressure.

PMID- 15154968
TI  - Can a "good death" be made better?: A preliminary evaluation of a patient-centred
      quality improvement strategy for severely ill in-patients.
AB  - BACKGROUND: Prior studies attempting to improve end-of-life care have focused on
      specific outcomes deemed important to healthcare providers, with disappointing
      results. Improvement may be best achieved by identifying concerns important to
      individual patients, communicating the patients' concerns to the treating medical
      team, and repeating the process frequently until all concerns are addressed. Our
      objective was to conduct a preliminary evaluation of this innovative patient
      centred quality improvement strategy. METHODS: Initial interviews elicited
      participants' ideas for improvement, which were then fed back to health care
      providers by the study investigator. A rapid-cycle change model ensured frequent
      reassessment and continued feedback. The study involved 36 seriously ill,
      hospitalized patients on teaching general medical inpatient units of a tertiary
      care hospital. The main outcome measure was participants' ratings of satisfaction
      within different domains of care on follow-up interviews. RESULTS: The proportion
      of participants who rated various aspects of their care as "excellent" or "very
      good" on initial interview was 72% for overall care, 64% for symptom control, 66%
      for level of support, and 75% for discussions about life sustaining treatments.
      Patients and families identified many actionable steps for improvement such as;
      better control of pain and shortness of breath, better access to physicians and
      medical information, more help with activities of daily living, improving the
      patient's environment, and shorter waits for nursing care, diagnosis, and
      treatment. Following feedback to the clinical team, participants reported
      improvement in overall care (32%), symptom control (44%), and support (40%). Only
      a minority had further discussions about life sustaining treatments. CONCLUSION:
      A patient-centred approach using rapid-cycle change was feasible and shows
      promise for improving the quality of end-of-life care. It should be evaluated on
      a larger sample in a controlled trial.

PMID- 15154969
TI  - A novel approach in the treatment of neuroendocrine gastrointestinal tumors:
      additive antiproliferative effects of interferon-gamma and meta
      iodobenzylguanidine.
AB  - BACKGROUND: Therapeutic options to effectively inhibit growth and spread of
      neuroendocrine gastrointestinal tumors are still limited. As both meta
      iodobenzylguanidine (MIBG) and interferon-gamma (IFNgamma) cause antineoplastic
      effects in neuroendocrine gastrointestinal tumor cells, we investigated the
      antiproliferative effects of the combination of IFNgamma and non-radiolabeled
      MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells.
      METHODS AND RESULTS: IFNgamma receptors were expressed in both models. IFNgamma
      dose- and time-dependently inhibited the growth of both STC-1 and of BON tumor
      cells with IC50-values of 95 +/- 15 U/ml and 135 +/- 10 U/ml, respectively. Above
      10 U/ml IFNgamma induced apoptosis-specific caspase-3 activity in a time
      dependent manner in either cell line and caused a dose-dependent arrest in the S
      phase of the cell cycle. Furthermore, IFNgamma induced cytotoxic effects in NE
      tumor cells. The NE tumor-targeted drug MIBG is selectively taken up via
      norepinephrine transporters, thereby specifically inhibiting growth in NE tumor
      cells. Intriguingly, IFNgamma treatment induced an upregulation of norepinephrine
      transporter expression in neuroendocrine tumors cells, as determined by semi
      quantitative RT-PCR. Co-application of sub-IC50 concentrations of IFNgamma and
      MIBG led to additive growth inhibitory effects, which were mainly due to
      increased cytotoxicity and S-phase arrest of the cell cycle. CONCLUSION: Our data
      show that IFNgamma exerts antiproliferative effects on neuroendocrine
      gastrointestinal tumor cells by inducing cell cycle arrest, apoptosis and
      cytotoxicity. The combination of IFNgamma with the NE tumor-targeted agent MIBG
      leads to effective growth control at reduced doses of either drug. Thus, the
      administration of IFNgamma alone and more so, in combination with MIBG, is a
      promising novel approach in the treatment of neuroendocrine gastrointestinal
      tumors.

PMID- 15154970
TI  - Socioeconomic and physical distance to the maternity hospital as predictors for
      place of delivery: an observation study from Nepal.
AB  - BACKGROUND: Although the debate on the safety and women's right of choice to a
      home delivery vs. hospital delivery continues in the developed countries, an
      undesirable outcome of home delivery, such as high maternal and perinatal
      mortality, is documented in developing countries. The objective was to study
      whether socio-economic factors, distance to maternity hospital, ethnicity, type
      and size of family, obstetric history and antenatal care received in present
      pregnancy affected the choice between home and hospital delivery in a developing
      country. METHODS: This cross-sectional study was done during June, 2001 to
      January 2002 in an administratively and geographically well-defined territory
      with a population of 88,547, stretching from urban to adjacent rural part of
      Kathmandu and Dhading Districts of Nepal with maximum of 5 hrs of distance from
      Maternity hospital. There were no intermediate level of private or government
      hospital or maternity homes in the study area. Interviews were carried out on 308
      women who delivered within 45 days of the date of the interview with a pre-tested
      structured questionnaire. RESULTS: A distance of more than one hour to the
      maternity hospital (OR = 7.9), low amenity score status (OR = 4.4), low education
      (OR = 2.9), multi-parity (OR = 2.4), and not seeking antenatal care in the
      present pregnancy (OR = 4.6) were statistically significantly associated with an
      increased risk of home delivery. Ethnicity, obstetric history, age of mother,
      ritual observance of menarche, type and size of family and who is head of
      household were not statistically significantly associated with the place of
      delivery. CONCLUSIONS: The socio-economic standing of the household was a
      stronger predictor of place of delivery compared to ethnicity, the internal
      family structure such as type and size of family, head of household, or
      observation of ritual days by the mother of an important event like menarche. The
      results suggested that mothers, who were in the low-socio-economic scale,
      delivered at home more frequently in a developing country like Nepal.

PMID- 15154971
TI  - Partially responsive celiac disease resulting from small intestinal bacterial
      overgrowth and lactose intolerance.
AB  - BACKGROUND: Celiac disease is a common cause of chronic diarrhea and
      malabsorption syndrome all over the world. Though it was considered uncommon in
      India in past, it is being described frequently recently. Some patients with
      celiac disease do not improve despite gluten free diet (GFD). A study described
      15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial
      overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE
      PRESENTATION: During a three-year period, 12 adult patients with celiac disease
      were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in
      northern India. Two of these 12 patients (16.6%), who did not fully respond to
      GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and
      lactose intolerance in the other. The former patient responded to antibiotics and
      the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In
      patients with celiac disease partially responsive or unresponsive to GFD, SIBO
      and lactose intolerance should be suspected; appropriate investigations and
      treatment for these may result in complete recovery.

PMID- 15154972
TI  - A novel method for evaluation and screening of caspase inhibitory peptides by the
      amino acid positional fitness score.
AB  - BACKGROUND: Since caspases are key executioners of apoptosis in cases of severe
      diseases including neurodegenerative disorders such as Alzheimer's disease and
      Huntington's disease, and viral infection diseases such as AIDS and hepatitis,
      potent and specific inhibitors of caspases have clinical potential. A series of
      peptide inhibitors has been designed based on cleavage sites of substrate
      proteins. However, these peptides are not necessarily the most potent to each
      caspase. Moreover, so far, it has proved to be difficult to design potent and
      specific peptide inhibitors of each caspase from sequence data of known cleavage
      sites in substrate proteins. We have attempted to develop a computational
      screening system for rapid selection of potent and specific peptide inhibitors
      from a comprehensive peptide library. RESULTS: We developed a new method for
      rapid evaluation and screening of peptide inhibitors based on Amino acid
      Positional Fitness (APF) score. By using this score, all known peptide inhibitors
      of each caspases-3,-7,-8, and -9 were rapidly selected in their enriched
      libraries. In this libraries, there were good correlations between predicted
      binding affinities of the known peptide inhibitors and their experimental Ki
      values. Furthermore, a novel potent peptide inhibitor, Ac-DNLD-CHO, for caspase-3
      was able to be designed by this method. To our knowledge, DNLD is a first
      reported caspase-3 inhibitory peptide identified by using the computational
      screening strategy. CONCLUSION: Our new method for rapid screening of peptide
      inhibitors using APF score is an efficient strategy to select potent and specific
      peptide inhibitors from a comprehensive peptide library. Thus, the APF method has
      the potential to become a valuable approach for the discovery of the most
      effective peptide inhibitors. Moreover, it is anticipated that these peptide
      inhibitors can serve as leads for further drug design and optimization of small
      molecular inhibitors.

PMID- 15154974
TI  - A multivantaged behavioural method for measuring onset and sequence of the
      clinical actions of antidepressants.
AB  - An aim in development of new antidepressants (ADs) now includes increasing speed
      of action. New drugs are tested primarily in outpatients who are less severely
      depressed than the patients treated in earlier trials of the tricyclic drugs. To
      determine early efficacy requires measures sensitive to initial changes in
      components of the illness as well as in the severity of the entire syndrome of
      depression. This paper describes the development of a brief 'multivantaged' (MV)
      method for assessing the major behavioural and affective components of
      depression. The revised Brief MV was significantly reduced from the original to
      make it more feasible to apply in outpatient studies. In this study we determined
      the Brief MV's (1) reliability and comparability to the original and (2) its
      ability to detect the onset of specific behavioural effects in outpatients
      treated with paroxetine for 6 wk. The latter is compared to the ability of the
      Hamilton Depression Scale (HAMD) to detect changes in global severity. The
      constructs derived from the Brief MV were found to be highly similar to those of
      the original version and as reliable. In depressed patients who responded to
      paroxetine, the HAMD and MV detected onset of improvement after 7 d of treatment.
      The Brief MV revealed that the improvement in global severity was due to the
      drug's action at this time on behaviours such as anxiety and distressed
      expression, as well as on a severity dimension of anxiety-agitation-somatization.
      Thus, the Brief MV, in uncovering underlying behavioural actions, represents an
      important addition to the current unidimensional HAMD approach in drug research.

PMID- 15154973
TI  - In silico identification and expression of SLC30 family genes: an expressed
      sequence tag data mining strategy for the characterization of zinc transporters'
      tissue expression.
AB  - BACKGROUND: Intracellular zinc concentration and localization are strictly
      regulated by two main protein components, metallothioneins and membrane
      transporters. In mammalian cells, two membrane transporters family are involved
      in intracellular zinc homeostasis: the uptake transporters called SLC39 or Zip
      family and the efflux transporters called SLC30 or ZnT family. ZnT proteins are
      members of the cation diffusion facilitator (CDF) family of metal ion
      transporters. RESULTS: From genomic databanks analysis, we identified the full
      length sequences of two novel SLC30 genes, SLC30A8 and SLC30A10, extending the
      SLC30 family to ten members. We used an expressed sequence tag (EST) data mining
      strategy to determine the pattern of ZnT genes expression in tissues. In silico
      results obtained for already studied ZnT sequences were compared to experimental
      data, previously published. We determined an overall good correlation with
      expression pattern obtained by RT-PCR or immunomethods, particularly for highly
      tissue specific genes. CONCLUSION: The method presented herein provides a useful
      tool to complete gene families from sequencing programs and to produce
      preliminary expression data to select the proper biological samples for
      laboratory experimentation.

PMID- 15154975
TI  - Repetitive transcranial magnetic stimulation (rTMS) in the double-blind treatment
      of a depressed patient suffering from bulimia nervosa: a case report.

PMID- 15154976
TI  - Focus on CaMKII: a molecular switch in the pathophysiology and treatment of mood
      and anxiety disorders.

PMID- 15154978
TI  - Separation and identification of 20 chemical constituents in the traditional
      Chinese medicinal preparation Shenbao tablet by LC-ESI-MS3.
AB  - A sensitive and specific high-performance liquid chromatography (HPLC)
      electrospray ionization multiple-stage mass spectrometry for the simultaneous
      separation and identification of 20 chemical constituents in the traditional
      Chinese medicinal preparation of the Shenbao tablet is established. The samples
      are separated with an Alltima C(18) column (250 x 4.6 mm, 5 microm) by linear
      gradient elution using water-acetic acid (A; 100:0.5, v/v) and acetonitrile (B; 0
      min, 76:24; 15 min, 70:30; 40 min, 53:47; 50 min, 30:70; and maintain 10 min) as
      the mobile phase at a flow rate of 1.0 mL/min. The ion trap mass spectrometer is
      coupled to the HPLC system. Satisfactory results are obtained within 60 min for
      the simultaneous separation and identification of the 20 constituents. This is
      the first report on the analysis of main chemical constituents in the Shenbao
      tablet.

PMID- 15154979
TI  - Establishing a selectivity survey as part of the method development activity for
      an isocratic reversed-phase liquid chromatographic method.
AB  - Often high-performance liquid chromatography method development is done by
      choosing a single C18 column and optimizing only the mobile phase composition. In
      this paper, it is demonstrated how to evaluate and optimize the best combination
      of the different stationary phase chemistries and mobile phases for a limited
      method development activity. By using column and mobile phase switching, it is
      possible to automate most of the activity in a nine-step process. Columns are
      chosen to represent the range of selectivity currently available. Interestingly,
      although the most popular column is the C18 phase, it is not the best column for
      the optimized methods in the cases studied.

PMID- 15154977
TI  - HPLC determination and pharmacokinetics of chlorogenic acid in rabbit plasma
      after an oral dose of Flos Lonicerae extract.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC) method has
      been developed for the determination of chlorogenic acid (3-O-caffeoyl-D-quinic
      acid) in plasma and applied to its pharmacokinetic study in rabbits after
      administration of Flos Lonicerae extract. Plasma samples are extracted with
      methanol. HPLC analysis of the extracts is performed on a C(18) reversed-phase
      column using acetonitrile-0.2% phosphate buffer (11:89, v/v) as the mobile phase.
      The UV detector is set at 327 nm. The standard curves are linear in the range
      0.0500-1.00 microg/mL (r = 0.9987). The mean extraction recovery of 85.1% is
      obtained for chlorogenic acid. The interday precision (relative standard
      deviation) ranges from 5.0% to 7.5%, and the intraday precision is better than
      9.0%. The limit of quantitation is 0.0500 microg/mL. The plasma concentration of
      chlorogenic acid shows a C(max) of 0.839 +/- 0.35 microg/mL at 34.7 +/- 1.1 min
      and a second one of 0.367 +/- 0.16 microg/mL at 273.4 +/- 39.6 min.

PMID- 15154980
TI  - Microwave-assisted extraction and quantitative analysis of high-density
      polyethylene pellets fortified with flavors.
AB  - Microwave-assisted extraction (MAE) has been shown to be an easy, rapid,
      accurate, quantitative, and precise component of an overall method for the
      quantitative analysis of flavor components formulated into high-density
      polyethylene (HDPE) pellets. Under optimized extraction conditions, MAE can be
      perform extraction of flavors from pellets within 1/2 h with flavor recoveries
      ranging from approximately 90% to 100%. The variability in the data expressed as
      percent relative standard deviation from gas chromatographic-mass selective
      detector analysis of targeted flavor components is always less than 5%,
      indicating a precise method. In addition, the major components identified in the
      flavor formulation prior to formulation into the HDPE pellets are the major
      components detected in the extraction, indicating an accurate determination.
      Thus, MAE can be readily recommended as an essential component of a high-volume
      approach to the quantitative determination of flavors formulated into HDPE
      pellets.

PMID- 15154981
TI  - High-performance liquid chromatography and thin-layer chromatography assays for
      Devil's Club (Oplopanax horridus).
AB  - Devil's root, Oplopanax horridus, is a widely used folk medicine in Alaska and
      British Columbia. The inner bark of the root and stem has been used to treat
      colds, cough, fever, and diabetes. The present study involves the development of
      high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC)
      methods to detect the presence of trans-nerolidol and sterols in the root bark.
      The HPLC and TLC analytical methods presented are suitable for the
      characterization and identification of Oplopanax horridus.

PMID- 15154982
TI  - Measurement of trihalomethanes and methyl tertiary-butyl ether in tap water using
      solid-phase microextraction GC-MS.
AB  - The prevalence of water disinfection byproducts in drinking water supplies has
      raised concerns about possible health effects from chronic exposure to these
      compounds. To support studies exploring the relation between exposure to
      trihalomethanes (THMs) and health effects, we have developed an automated
      analytical method using headspace solid-phase microextraction coupled with
      capillary gas chromatography and mass spectrometry. This method quantitates trace
      levels of THMs (chloroform, bromodichloromethane, dibromochloromethane, and
      bromoform) and methyl tertiary-butyl ether in tap water. Detection limits of less
      than 100 ng/L for all analytes and linear ranges of three orders of magnitude are
      adequate for measuring the THMs in tap water samples tested from across the
      United States. THMs are stable for extended periods in tap water samples after
      quenching of residual chlorine and buffering to pH 6.5, thus enabling larger
      epidemiologic field studies with simplified sample collection protocols.

PMID- 15154983
TI  - Determination of mangiferin, jateorrhizine, palmatine, berberine, cinnamic acid,
      and cinnamaldehyde in the traditional Chinese medicinal preparation Zi-Shen pill
      by high-performance liquid chromatography.
AB  - High-performance liquid chromatography is employed to determine the contents of
      six marker components such as mangiferin, jateorrhizine, palmatine, berberine,
      cinnamic acid, and cinnamaldehyde in the traditional Chinese medicinal
      preparation Zi-Shen pill. The separation is performed on a C(18) column by
      stepwise gradient elution with water (0.2%, v/v, triethylamine adjusted to pH 4
      with phosphoric acid)-methanol-acetonitrile (0.01 min, 98:0:2; 20 min, 80:5:15;
      30 min, 65:13:22; and 55 min, 65:13:22) as the mobile phase at a flow rate of 0.9
      mL/min, with UV detection at 280 nm. Six regression equations show good linear
      relationships between the peak area of each marker and concentration. The
      recoveries of the markers listed are 95.5%, 98.3%, 96.8%, 99.5%, 101.7%, and
      102.1%, respectively. The repeatability and reproducibility (relative standard
      deviation) of the method are less than 2.5% and 3.3%, respectively.

PMID- 15154984
TI  - Evaluation of pressurized liquid extraction and pressurized hot water extraction
      for tanshinone I and IIA in Salvia miltiorrhiza using LC and LC-ESI-MS.
AB  - Pressurized liquid extraction (PLE) and pressurized hot water extraction (PHWE)
      using a laboratory-made system are applied for the extraction of thermally labile
      components such as tanshinone I and IIA in Salvia miltiorrhiza. PLE and PHWE are
      carried out dynamically at a flow of 1 mL/min, temperature between 95-140 degrees
      C, applied pressure of 10-20 bars, and extraction times of 20 and 40 min,
      respectively. Effects of ethanol added into the water used in PHWE are explored.
      PLE is found to give comparable or higher extraction efficiencies compared with
      PHWE with reference to Soxhlet extraction for tanshinone I and IIA in Salvia
      miltiorrhiza. The tanshinone I and IIA present in the various medicinal plant
      extracts are determined by liquid chromatography and liquid chromatography-mass
      spectrometry.

PMID- 15154985
TI  - Fast and accurate determination of arsenobetaine in fish tissues using
      accelerated solvent extraction and HPLC-ICP-MS determination.
AB  - A high-performance liquid chromatography-inductively coupled plasma-mass
      spectrometry (HPLC-ICP-MS) method has been developed for the fast and accurate
      analysis of arsenobetaine (AsB) in fish samples extracted by accelerated solvent
      extraction. The combined extraction and analysis approach is validated using
      certified reference materials for AsB in fish and during a European
      intercomparison exercise with a blind sample. Up to six species of arsenic (As)
      can be separated and quantitated in the extracts within a 10-min isocratic
      elution. The method is optimized so as to minimize time-consuming sample
      preparation steps and allow for automated extraction and analysis of large sample
      batches. A comparison of standard addition and external calibration show no
      significant difference in the results obtained, which indicates that the LC-ICP
      MS method is not influenced by severe matrix effects. The extraction procedure
      can process up to 24 samples in an automated manner, yet the robustness of the
      developed HPLC-ICP-MS approach is highlighted by the capability to run more than
      50 injections per sequence, which equates to a total run-time of more than 12 h.
      The method can therefore be used to rapidly and accurately assess the proportion
      of nontoxic AsB in fish samples with high total As content during toxicological
      screening studies.

PMID- 15154987
TI  - The circle of health: a health definition model.
AB  - Beginning with a holistic definition in ancient times, the predominant American
      definition of health now focuses on physical health and disease symptoms. This
      limited definition of health is an inadequate foundation for holistic health care
      strategies. This article provides a conceptual model with an expanded definition
      of health as a basis for holistic and conventional health strategies. The model
      includes concepts of balance, energy systems, and mind-body integration from non
      Western health practices. A holistic definition of health suggests an expanded
      range of positive, pleasurable health behaviors. The visual representation of the
      model can be used by health care professionals and clients to identify disease
      reduction strategies or a health improvement program for well individuals.
      Understanding and expanding the conceptualization of health and health
      improvement strategies offers the possibility of improving client satisfaction
      and health status outcomes.

PMID- 15154988
TI  - The experience of using a combination of complementary therapies: a journey of
      balance through self-healing.
AB  - Literature on complementary or alternative therapies from the perspective of
      personal experience is limited, and to date, there are no published studies using
      a qualitative approach to study the contextual effects of combined complementary
      therapies. Evaluating the use of combinations of complementary therapies from the
      perspective of those who experience them is important in understanding their
      beneficial and synergistic effects. This article is a report of the findings of a
      hermeneutic phenomenological study on the lived experience of 8 guests
      participating in a structured naturopathic program that used combinations of
      complementary/alternative therapies to promote healing in illness.

PMID- 15154989
TI  - Men of prayer: spirituality of men with prostate cancer: a grounded theory study.
AB  - Spirituality plays a powerful role in cancer treatment and recovery; it has been
      identified by hospitalized patients as one of their top priorities of care.
      However, health care providers struggle to find ways to address the spirituality
      of their patients. The purposes of this study were to discover what spirituality
      means for men with prostate cancer and how it influences their treatment. Eleven
      men, ages 54 to 71, with prostate cancer were interviewed within several days
      following radical prostatectomy with bilateral lymph node staging. This grounded
      theory methodology generated three categories of spirituality: (a) praying, (b)
      receiving support, and (c) coping with cancer. The basic social process, coping
      with cancer, occurred in four phases: facing cancer, choosing treatment,
      trusting, and living day by day. These results were validated by four of the
      participants for truthfulness. The findings of this study provide holistic nurses
      with knowledge and a midrange theory of spirituality that can be used in building
      a research-based practice.

PMID- 15154990
TI  - "Making special": a framework for understanding the art of holistic nursing.
AB  - Holistic nurses demonstrate interest in and concern for aesthetics in nursing;
      however, the relationship of holistic nursing to aesthetics in nursing lacks
      clarity. Challenges to the study of aesthetics in nursing arise from too little
      discourse on the topic and lack of consensus on language and methods of inquiry.
      Nevertheless, aesthetic knowing is a fundamental pattern of knowing in nursing
      and the one that mediates and integrates all other patterns of knowing in nursing
      action. A behavioral theory of aesthetics provides a framework for exploring the
      relationship of holistic nursing to aesthetic knowing and the art of nursing.
      Synthesis of this framework with holistic nursing core values and standards of
      practice suggests that holistic nursing is more than perspective; it is an
      aesthetic.

PMID- 15154991
TI  - A meta-analysis of the effect of guided imagery practice on outcomes.
AB  - Guided imagery is an intervention used by nurses in a variety of settings. It has
      been suggested that better outcomes will occur with continued practice. No
      studies were found that examined the relationship between practice duration and
      strength of outcomes. The focus of this meta-analysis was the effect size of
      guided imagery intervention studies with different durations. Statistical
      findings of 10 studies of various durations were converted to d statistics and
      plotted against the duration of study. The results show an increase in effect
      size of guided imagery over the first 5 to 7 weeks; however, the effect was
      decreased at 18 weeks.

PMID- 15154992
TI  - From expert to novice: The unnerving transition from experienced RN to neophyte
      APN.
AB  - Following analysis of a critical incident, we discuss role identity stressors
      during knowledge acquisition. Specifically, we examine one nurse's supposition
      that expert knowledge is automatically transferable despite having a different
      role expectation. We share the unexpectedly powerful and potentially ego
      deflating experience of one advanced practice nurse (APN) student preparing for
      the challenge of transitioning from novice to expert as a new APN. However, the
      greater lesson learned was failing to appreciate the transition in role identity
      from expert to novice that one undergoes as a registered nurse (RN) to APN
      student.

PMID- 15154993
TI  - Faculty response to faculty-nurse mentoring.

PMID- 15154994
TI  - Pancreatic transplantation: evaluation and management.
AB  - More than 2 million people in the United States have type 1 diabetes mellitus.
      Pancreatic transplantation has emerged as the single most effective means of
      achieving normal glucose homeostasis in this patient population. Newer
      immunosuppressive agents and surgical techniques continue to evolve, resulting in
      improved long-term graft and patient survival. Herein, an understanding of the
      evaluation, technical aspects, and perioperative management of pancreas
      transplantation is outlined.

PMID- 15154995
TI  - Pediatric acute hypoxemic respiratory failure: management of oxygenation.
AB  - Acute hypoxemic respiratory failure (AHRF) is one of the hallmarks of acute lung
      injury (ALI) and acute respiratory distress syndrome (ARDS), which are caused by
      an inflammatory process initiated by any of a number of potential systemic and/or
      pulmonary insults that result in heterogeneous disruption of the capillary
      pithelial interface. In these critically sick patients, optimizing the management
      of oxygenation is crucial. Physicians managing pediatric patients with ALI or
      ARDS are faced with a complex array of options influencing oxygenation. Certain
      treatment strategies can influence clinical outcomes, such as a lung protective
      ventilation strategy that specifies a low tidal volume (6 mL/kg) and a plateau
      pressure limit (30 cm H(2)O). Other strategies such as different levels of
      positive end expiratory pressure, altered inspiration to expiration time ratios,
      recruitment maneuvers, prone positioning, and extraneous gases or drugs may also
      affect clinical outcomes. This article reviews state-of-the-art strategies on the
      management of oxygenation in acute hypoxemic respiratory failure in children.

PMID- 15154996
TI  - Clinical informatics in critical care.
AB  - Health care information systems have the potential to enable better care of
      patients in much the same manner as the widespread use of the automobile and
      telephone did in the early 20th century. The car and phone were rapidly accepted
      and embraced throughout the world when these breakthroughs occurred. However, the
      automation of health care with use of computerized information systems has not
      been as widely accepted and implemented as computer technology use in all other
      sectors of the global economy. In this article, the authors examine the need,
      risks, and rewards of clinical informatics in health care as well as its specific
      relationship to critical care medicine.

PMID- 15154997
TI  - Preliminary experience with nesiritide in the pediatric population.
AB  - Nesiritide is a recombinant formulation of brain-type natriuretic factor.
      Preliminary experience in the adult population suggests that nesiritide may be an
      effective agent in the treatment of decompensated congestive heart failure. Given
      its physiologic effects, it may be an effective agent in the pediatric
      population; however, to date, there are no reports regarding its use in infants
      and children. The authors retrospectively review their experience with nesiritide
      in 5 pediatric patients. The cohort of 5 patients included a diverse population
      with 2 patients who were status postcardiothoracic surgery, 2 with adult
      respiratory distress syndrome, and 1 in the recovery phase from septic shock.
      Although no direct measurement of cardiac output was feasible as none of the
      patients had a pulmonary artery catheter, other indicators of increased cardiac
      output were noted. These included improved peripheral perfusion with warming of
      the extremities and improvement of peripheral pulses in all of the patients,
      increased venous saturation in 2 of the patients, and maintenance of or increased
      urine output despite weaning or discontinuation of diuretics. In 3 of the
      patients, nesiritide was started as the primary agent to provide a decrease in
      systemic vascular resistance and augment cardiac output, while in the other 2
      patients, nesiritide was used when other vasoactive agents failed to provide the
      desired effect or resulted in adverse effects.

PMID- 15154998
TI  - Is there a use for nesiritide in pediatric patients?

PMID- 15155002
TI  - The golden age.

PMID- 15155003
TI  - Are humans seasonally photoperiodic?
AB  - Humans exhibit seasonal variation in a wide variety of behavioral and
      physiological processes, and numerous investigators have suggested that this
      might be because we are sensitive to seasonal variation in day length. The
      evidence supporting this hypothesis is inconsistent. A new hypothesis is offered
      here-namely, that some humans indeed are seasonally photoresponsive, but others
      are not, and that individual variation may be the cause of the inconsistencies
      that have plagued the study of responsiveness to photoperiod in the past. This
      hypothesis is examined in relation to seasonal changes in the reproductive
      activity of humans, and it is developed by reviewing and combining five bodies of
      knowledge: correlations of human birthrates with photoperiod; seasonal changes in
      the activity of the neuroendocrine pathway that could link photoperiod to gonadal
      steroid secretion in humans; what is known about photoperiod, latitude, and
      reproduction of nonhuman primates; documentation of individual variation in
      photoresponsiveness in rodents and humans; and what is known about the
      evolutionary ecology of humans.

PMID- 15155004
TI  - The decline in human seasonality.

PMID- 15155006
TI  - Plasticity of circadian behavior and the suprachiasmatic nucleus following
      exposure to non-24-hour light cycles.
AB  - Period aftereffects are a form of behavioral plasticity in which the free-running
      period of circadian behavior undergoes experience-dependent changes. It is
      unclear whether this plasticity is age dependent and whether the changes in
      behavioral period relate to changes in the SCN or the retina, 2 known circadian
      pacemakers in mammals. To determine whether these changes vary with age, Per1-luc
      transgenic mice (in which the luciferase gene is driven by the Period1 promoter)
      of different ages were exposed to short (10 h light: 10 h dark, T20) or long (14
      h light: 14 h dark, T28) light cycles (T cycles). Recordings of running-wheel
      activity in constant darkness (DD) revealed that the intrinsic periods of T20
      mice were significantly shorter than of T28 mice at all ages. Aftereffects
      following the shorter light cycle were significantly smaller in mice older than 3
      months, corresponding with a decreased ability to entrain to T20. Age did not
      diminish entrainment or aftereffects in the 28-h light schedule. The behavioral
      period of pups born in DD depended on the T cycle experienced in utero, showing
      maternal transference of aftereffects. Recordings of Per1-luc activity from the
      isolated SCN in vitro revealed that the SCN of young mice expressed aftereffects,
      but the periods of behavior and SCN were negatively correlated. Enucleation in DD
      had no effect on behavioral aftereffects, indicating the eyes are not required
      for aftereffects expression. These data show that circadian aftereffects are an
      age-dependent form of plasticity mediated by stable changes in the SCN and,
      importantly, extra-SCN tissues.

PMID- 15155008
TI  - Effects of photoperiod on rat motor activity rhythm at the lower limit of
      entrainment.
AB  - The experiment described here studied the rat motor activity pattern as a
      function of the photoperiod of circadian light-dark cycles in the limits of
      entrainment (22-and 23-h periods). In most cases, the overt rhythm showed 2
      circadian components: 1 that followed the external LD cycle and a 2nd rhythm that
      was free run. The expression of these components was directly dependent on the
      photoperiod, and there was a gradual transition in the manifestation of 1 or the
      other. The component with a period equal to that of the external cycle was more
      manifested under long photoperiods, while the other 1 was more expressed during
      short photoperiods. Also, the period of the free-running component was longer
      under T22 than T23. For each period, the free-running component was longer under
      a longer photoperiod. At first sight, the presence of these 2 components in most
      of the rats might appear to be due to the fact that in the limits of entrainment,
      some rats do not entrain and thus show a free-running rhythm plus masking.
      However, the gradation observed in the different patterns of the overt motor
      activity rhythm, especially those patterns related to the different balance
      between the 2 components and the length of the period of the free-running
      component under LD as a function of the photoperiod, suggests that the circadian
      system can be functionally dissociated.

PMID- 15155007
TI  - High potassium treatment resets the circadian oscillator in Xenopus retinal
      photoreceptors.
AB  - In vertebrate retina, light hyperpolarizes the photoreceptor membrane, and this
      is an essential cellular signal for vision. Cellular signals responsible for
      photic entrainment of some circadian oscillators appear to be distinct from those
      for vision, but it is not known whether changes in photoreceptor membrane
      potential play roles in photic entrainment of the photoreceptor circadian
      oscillator. The authors show that a depolarizing exposure to high potassium
      resets the circadian oscillator in cultured Xenopus retinal photoreceptor layers.
      A 4-h pulse of high [K(+)] (34 mM higher than in normal culture medium) caused
      phase shifts of the melatonin rhythm. This treatment caused phase delays during
      the early subjective day and phase advances during the late subjective day. In
      addition to the phase-shifting effect, high potassium pulses stimulated melatonin
      release acutely at all times. High [K(+)] therefore mimicked dark in its effects
      on oscillator phase and melatonin synthesis. These results suggest that membrane
      potential may play a role in photic entrainment of the photoreceptor circadian
      oscillator and in regulation of melatonin release.

PMID- 15155009
TI  - Feeding schedule controls circadian timing of daily torpor in SCN-ablated
      Siberian hamsters.
AB  - Timing of daily torpor was assessed in suprachiasmatic nucleus-ablated (SCNx) and
      sham-ablated Siberian hamsters fed restricted amounts of food each day either in
      the light or dark phase of a 14:10 light-dark cycle. Eighty-five percent of sham
      ablated and 45% of SCNx hamsters displayed a preferred hour for torpor onset. In
      each group, time of torpor onset was not random but occurred at a mean hour that
      differed significantly from chance. Time of food presentation almost completely
      accounted for the timing of torpor onset in SCNx animals and significantly
      affected timing of this behavior in intact hamsters. These results suggest that
      the circadian pacemaker in the SCN controls the time of torpor onset indirectly
      by affecting timing of food intake, rather than by, or in addition to, direct
      neural and humoral outputs to relevant target tissues.

PMID- 15155010
TI  - Circadian organization of a subarctic rodent, the northern red-backed vole
      (Clethrionomys rutilus).
AB  - Arctic and subarctic environments are exposed to extreme light: dark (LD)
      regimes, including periods of constant light (LL) and constant dark (DD) and
      large daily changes in day length, but very little is known about circadian
      rhythms of mammals at high latitudes. The authors investigated the circadian
      rhythms of a subarctic population of northern red-backed voles (Clethrionomys
      rutilus). Both wild-caught and third-generation laboratory-bred animals showed
      predominantly nocturnal patterns of wheel running when exposed to a 16:8 LD
      cycle. In LL and DD conditions, animals displayed large phenotypic variation in
      circadian rhythms. Compared to wheel-running rhythms under a 16:8 LD cycle, the
      robustness of circadian activity rhythms decreased among all animals tested in LL
      and DD (i.e., decreased chi-squared periodogram waveform amplitude). A large
      segment of the population became noncircadian (60% in DD, 72% in LL) within 8
      weeks of exposure to constant lighting conditions, of which the majority became
      ultradian, with a few individuals becoming arrhythmic, indicating highly labile
      circadian organization. Wild-caught and laboratory-bred animals that remained
      circadian in wheel running displayed free-running periods between 23.3 and 24.8
      h. A phase-response curve to light pulses in DD showed significant phase delays
      at circadian times 12 and 15, indicating the capacity to entrain to rapidly
      changing day lengths at high latitudes. Whether this phenotypic variation in
      circadian organization, with circadian, ultradian, and arrhythmic wheel-running
      activity patterns in constant lighting conditions, is a novel adaptation to life
      in the arctic remains to be elucidated.

PMID- 15155011
TI  - Phase relationships between sleep-wake cycle and underlying circadian rhythms in
      Morningness-Eveningness.
AB  - A shorter phase angle between habitual wake time and underlying circadian rhythms
      has been reported in evening types (E types) compared to morning-types (M types).
      In this study, phase angles were compared between 12 E types and 12 M types to
      verify if this difference was observed when the sleep schedule was relatively
      free from external social constraints. Subjects were selected according to their
      Morningness-Eveningness Questionnaire score (MEQ score). There were 6 men and 6
      women in each group (ages 19-34 years), and all had a habitual sleep duration
      between 7 and 9 h. Sleep schedule was recorded by actigraphy and averaged over 7
      days. Circadian phase was estimated by the hour of temperature minimum (T(min))
      in a 26-h recording and by the timing of the onset of melatonin secretion (dim
      light melatonin onset [DLMO]) measured in saliva samples. Phase angles were
      defined as the interval between phase markers and averaged wake time. Results
      showed that, in the present experimental conditions, phase angles were very
      similar in the 2 groups of subjects. However, results confirmed the previously
      reported correlation between phase and phase angle, showing that a later
      circadian phase was associated with a shorter phase angle. Gender comparisons
      showed that for a same MEQ score, women had an earlier DLMO and a longer phase
      angle between DLMO and wake time. Despite a significant difference in the
      averaged circadian phases between E-type and M-type groups, there was an overlap
      in the circadian phases of the subjects of the 2 groups. Further comparisons were
      made between the 2 circadian types, separately for the subgroups with overlapping
      or nonoverlapping circadian phases. In both subgroups, the significant difference
      between MEQ scores, bedtimes, and wake times were maintained in the expected
      direction. In the subgroup with nonoverlapping circadian phases, phase angles
      were shorter in E-type subjects, in accordance with previous studies. However, in
      the overlapping subgroup, phase angles were significantly longer in E types
      compared to M types. Results suggest that the morningness-eveningness preference
      identified by the MEQ score refers to 2 distinct mechanisms, 1 associated with a
      difference in circadian period and phase of entrainment and the other associated
      with chronobiological aspects of sleep regulation.

PMID- 15155015
TI  - The effect of numerical statements of risk on trust and comfort with hypothetical
      physician risk communication.
AB  - OBJECTIVE: To contribute to the debate about whether numeric statements of risk
      ought to be included in risk communications. DESIGN: Subjects (n = 115) completed
      a questionnaire involving a physician risk communication and 4 scenarios, each of
      which described a patient with symptoms and signs potentially suggestive of
      cancer. Each scenario was presented in 3 risk communication versions (a verbal
      version and 2 numeric versions) in a within-subject 4 x 3 design. Subjects rated
      their trust in and comfort with the information and their belief that the
      physician distorted their risk level. RESULTS: Subjects were significantly more
      trusting of (t =4.0, P < 0.001) and comfortable with (t =3.4, P = 0.001) the risk
      information, less likely to believe that the physician minimized the risk in the
      numeric versions than verbal versions (t =4.3, P < 0.0001), and just as likely to
      believe that the physician exaggerated the risk in the 2 versions (P = 0.588).
      CONCLUSIONS: Including a numeric statement of risk in a risk communication can
      increase trust and belief in and comfort with the risk information.

PMID- 15155016
TI  - Prioritizing health care: is "health" always an appropriate maximand?
AB  - In recent years, a few health economists have begun to question the ethical
      underpinnings of the standard practice of quality-adjusted life year (QALY)
      maximization as a ubiquitous decision rule in the allocation of health care
      resources. Prominent among these is Erik Nord, who conjectures that QALY
      maximization discriminates against the chronically ill and disabled when
      prioritizing between different individuals (or groups of individuals) for life
      extending interventions. Nord has recommended that life years gained should
      always be given a weight equal to 1 in these circumstances. This article reports
      an experiment designed as an initial attempt at eliciting some of the thought
      processes employed by people when they prioritize life-saving health care
      interventions between patients who differ only in respect to the presence or
      absence of a disability. The results show that in the priority-setting contexts
      used, a majority of the respondents perceived the relative health status of the
      different patients as irrelevant, providing some tentative support for Nord's
      argument.

PMID- 15155014
TI  - Radiologist uncertainty and the interpretation of screening.
AB  - OBJECTIVE: To determine radiologists' reactions to uncertainty when interpreting
      mammography and the extent to which radiologist uncertainty explains variability
      in interpretive performance. METHODS: The authors used a mailed survey to assess
      demographic and clinical characteristics of radiologists and reactions to
      uncertainty associated with practice. Responses were linked to radiologists'
      actual interpretive performance data obtained from 3 regionally located
      mammography registries. RESULTS: More than 180 radiologists were eligible to
      participate, and 139 consented for a response rate of 76.8%. Radiologist gender,
      more years interpreting, and higher volume were associated with lower uncertainty
      scores. Positive predictive value, recall rates, and specificity were more
      affected by reactions to uncertainty than sensitivity or negative predictive
      value; however, none of these relationships was statistically significant.
      CONCLUSION: Certain practice factors, such as gender and years of interpretive
      experience, affect uncertainty scores. Radiologists' reactions to uncertainty do
      not appear to affect interpretive performance.

PMID- 15155018
TI  - Value of information literature analysis: a review of applications in health risk
      management.
AB  - This article provides the first comprehensive review of value of information
      (VOI) analyses related to health risk management published in English in peer
      reviewed journals by the end of 2001. VOI analysis represents a decision analytic
      technique that explicitly evaluates the benefit of collecting additional
      information to reduce or eliminate uncertainty. Through a content analysis of VOI
      applications, this article characterizes various attributes of VOI applications,
      shows the evolution of the methodology and advances in computing tools that allow
      analysis of increasingly complex problems, and suggests the need for some
      standardization of reporting methods and results. The authors' analysis shows a
      lack of cross-fertilization across topic areas and the tendency of articles to
      focus on demonstrating the usefulness of the VOI approach rather than
      applications to actual management decisions. This article provides important
      insights for VOI applications in medical decision making.

PMID- 15155017
TI  - New and dis-improved: on the evaluation and use of less effective, less expensive
      medical interventions.
AB  - The innovation and diffusion of new technologies is in large measure responsible
      for the persistent rise in the cost of health care. The increasing cost of health
      care, in turn, will make cost-saving technologies more attractive. When cost
      saving technologies lead to better or equivalent outcomes, their acceptance will
      not be controversial. However, the necessary conditions for the development and
      clinical acceptance of cost-saving technologies that might diminish the quality
      of health care have not been systematically considered. Indeed, as the clinical
      research enterprise has been focused almost entirely on quality-improving (or
      quality-neutral) innovations, new concepts may need to be introduced for quality
      reducing innovations. Although the development of such therapies would, at least
      in some circumstances, increase overall societal benefits, replacing a standard
      therapy with a less effective one may conflict with deeply held values, such that
      conventional cost-effectiveness benchmarks might not apply. In addition, from a
      clinical research perspective, there are considerable ethical and methodologic
      hurdles that might impede the development of less expensive, less intensive
      therapies. In this article, using a hypothetical scenario, the authors consider
      economic, ethical, and research design issues concerning the innovation and
      diffusion of less effective, less expensive therapies and introduce 2 concepts-
      "decremental cost-effectiveness" and "acceptability trials"--that may in part
      provide a research framework for the study of "new and dis-improved" therapies.

PMID- 15155021
TI  - Law and ethics.

PMID- 15155019
TI  - Meta-analysis of 2-treatment clinical trials including both continuous and
      dichotomous results.
AB  - To expedite the timely creation of medical practice guidelines, a meta-analytic
      method was developed to combine both dichotomous survival data and continuous
      physiologic data from multiple studies of differing experimental design, which
      compare the same innovative clinical intervention to standard care. An aggregate
      ratio, R*, of the observed treatment effect to a clinically optimal treatment
      effect for studies in a series is computed and compared to the 95% confidence
      limit for R* under the null hypothesis. Input data for continuous variables
      include sample means, standard errors, and sample sizes. Input data for
      dichotomous variables include group proportions and sizes. The analysis can be
      done using a simple, 1-page spreadsheet. It allows one to judge biological
      significance, to test for statistical significance, to compare subgroups of
      studies, to test for outliers, and to compute the power of the meta-analysis.
      These features are demonstrated for studies of interposed abdominal compression
      cardiopulmonary resuscitation.

PMID- 15155022
TI  - An open invitation to our readers.

PMID- 15155020
TI  - From diagnostic accuracy to accurate diagnosis: interpreting a test result with
      confidence.
AB  - BACKGROUND: The Standard for Reporting of Diagnostic Accuracy statement promotes
      the reporting of confidence intervals (CIs) for indices of diagnostic test
      accuracy. However, these indices must be combined with an estimate of pretest
      probability to properly interpret the results of such tests, thus yielding
      positive and negative predictive values. For small sample sizes, CI estimation
      for predictive values based on the classical logit transformation has been found
      to be very conservative. A method based on computer simulation has therefore been
      suggested as an alternative. METHODS: ACI procedure for predictive values that
      yields limits completely contained in those provided by the logit transformation
      is proposed and evaluated. RESULTS: The proposed approach to CI construction
      maintains nominal coverage very well even when sample sizes are small.
      CONCLUSION: Accurate CIs for positive and negative predictive values can be
      obtained without using computer simulation.

PMID- 15155023
TI  - Restorative activities of community-dwelling elders.
AB  - This study was conducted to identify the restorative activities of community
      dwelling elders. Exposure to restorative activities, such as observing nature, is
      associated with improved concentration, more effective cognitive functioning, and
      feelings of greater mental energy, peacefulness, and refreshment. Little
      literature exists regarding the types and benefits of restorative activities
      engaged in by elders, a group in need of means to promote optimal daily
      functioning. A qualitative descriptive design was used. Thirty (28 women, 2 men)
      community-dwelling elders (ages 65 to 92 years) were interviewed using open-ended
      questions to ascertain their perceptions of restorative activities. A content
      analysis of themes produced 12 categories of restorative activities: creative
      outlets, altruism, nature, social connections, cognitive challenges, physical
      activity, reading, family connections, spirituality and reflection, cultural
      activities, travel, and other activities. Additional studies with larger,
      culturally diverse samples and more men are warranted before implementing
      restorative interventions with elders in the hopes of promoting optimal
      functioning and well-being.

PMID- 15155026
TI  - An integrative review of the concept of spirituality in the health sciences.
AB  - Spirituality is a universal human phenomenon, yet confusion and incomprehension
      of the concept is ever-present. The purpose of this study was to explore how
      research on the concept of spirituality has been reported in the health
      literature in the past decade and develop an ontological and theoretical
      understanding of spirituality. The examination was based on quantitative and
      qualitative integrative review approaches, which integrated empirical research on
      spirituality. The sample included 73 spirituality research articles, which were
      published in English between January 1990 and September 2000. An electronic data
      collection tool was designed for use in this project and formatted using Excel
      software for transfer of coded data into the NVivo software for the data
      analysis. The results identified essential elements of spirituality, current use
      of operational definitions and instruments, conceptual frameworks used in
      spirituality research, and cultural aspects of spirituality. Historical
      comparison among decades and barriers in researching spirituality are discussed.

PMID- 15155027
TI  - Testing the barriers to healthy eating scale.
AB  - Clarifying barriers to dietary intake may identify factors that place pregnant
      women at risk for complications. This methodological study assessed the
      psychometric properties of the Barriers to Healthy Eating Scale. Item generation
      was based on constructs in Pender's health promotion model. The instrument was
      tested in two separate samples of pregnant women. Content validity was assessed,
      and construct validity testing resulted in an expected negative relationship
      between scores on the Barriers to Healthy Eating Scale and the Nutrition subscale
      of the Health Promoting Lifestyle Profile-II. Factor analysis resulted in a 5
      factor scale that explained 73% of the variance. Alpha coefficients for the total
      scale ranged from.73 to.77, and subscales ranged from.48 to.99. Test-retest
      reliability for the total scale was.79. The Barriers to Healthy Eating Scale
      appears to be a reliable and valid instrument to assess barriers that may impede
      healthy eating in pregnant women.

PMID- 15155028
TI  - Organizational lifecycle in a school of nursing.
AB  - This article is a historical case study of the organizational lifecycle of the
      DePauw University School of Nursing in Greencastle, Indiana. Few studies have
      examined schools of nursing over their entire lifecycles. The school was created
      in 1954, existed for 40 years, and closed in 1994. Organizational lifecycle
      theory posits that organizations undergo four stages: creation, transformation,
      decline, and closing or death. We used this theory to guide our study, which was
      based on data from interviews, archival documents, and institutional records. We
      found that factors associated with the creation of this organization had long
      lasting effects, the external environment profoundly influenced the school, and
      that a shift in shared values and institutional linkages contributed to its
      closure. As society's need and demand for nurses increases, the continuance of
      schools of nursing and reasons for their demise merits the attention of faculty
      and administrators.

PMID- 15155029
TI  - Internet intervention for community elders: process and feasibility.
AB  - The aim of this report is to describe the process and feasibility of having
      elders respond to standardized questionnaires in an Internet intervention program
      for caregivers of persons with dementia. Twenty-one persons with dementia (mean
      75 years), and their spouse caregivers (mean age of 65 years) used the
      intervention program and responded to the questionnaires. Results indicated that
      with adequate support, elderly caregiver participants were able to provide
      responses to standardized questionnaires comparable to scores found in other
      caregiver studies using traditional methods. Suggestions are provided for further
      testing.

PMID- 15155031
TI  - Warm and homely or cold and beautiful? Sex differences in trading off traits in
      mate selection.
AB  - Prior research and theory suggest that people use three main sets of criteria in
      mate selection: warmth/trustworthiness, attractiveness/vitality, and
      status/resources. In two studies, men and women made mating choices between pairs
      of hypothetical potential partners and were forced to make trade-offs among these
      three criteria (e.g., warm and homely vs. cold and attractive). As predicted,
      women (relative to men) placed greater importance on warmth/trustworthiness and
      status/resources in a potential mate but less importance on
      attractiveness/vitality. In addition, as expected (a) ratings of ideal standards
      partly mediated the link between sex and mate choices, (b) ideal standards
      declined in importance from long-term to short-term relationships, with the
      exception of attractiveness/vitality, and unexpectedly, (c) sex differences were
      higher for long-term (compared to short-term) mate choice. Explanations and
      implications are discussed.

PMID- 15155032
TI  - On the assignment of punishment: the impact of general-societal threat and the
      moderating role of severity.
AB  - This article reports experiments assessing how general threats to social order
      and severity of a crime can influence punitiveness. Results consistently showed
      that when participants feel that the social order is threatened, they behave more
      punitively toward a crime perpetrator, but only when severity associated with a
      crime was relatively moderate. Evidence is presented to suggest that people can
      correct-at least to a degree-for the "biasing" influence of these inductions.
      Finally, threats to social order appear to increase punitiveness by arousing a
      retributive desire to see individuals pay for what they have done, as opposed to
      a purely utilitarian desire to deter future wrongdoing. The authors suggest that
      individuals sometimes act as intuitive prosecutors when ascribing punishment to
      an individual transgressor based on their perception of general societal control
      efficacy.

PMID- 15155034
TI  - Trust and partner-enhancing attributions in close relationships.
AB  - A cross-lagged panel design was used to examine the links between trust and
      attributional processes in a sample of 75 married couples throughout a period of
      2 years. During the first phase of the study, participants completed a measure of
      marital trust, engaged in a laboratory problem-solving discussion of a recurrent
      conflict-related issue, and then rated their partner's behavior and motives.
      Approximately 2 years later, 54 couples were again contacted and measures of
      trust were obtained. Forty of these couples also viewed a videotape of their
      laboratory problem-solving discussion from 2 years previously and rated their
      partner's behavior and motives. Results suggested a reciprocal causal pattern by
      which partner-enhancing attributions predict changes in trust and trust predicts
      changes in partner-enhancing attributions.

PMID- 15155033
TI  - Work conditions and employees' self-set goals: goal processes enhance prediction
      of psychological distress and well-being.
AB  - Although previous theory and research suggest that employee well-being should be
      predicted by work conditions (viz., Karasek and colleagues' job demands-control
      social support [J-DCS] model), other factors are also likely to be important. In
      this study, the authors consider correlates of employee psychological distress
      and well-being using a goal-focused approach grounded in Ford's (1992)
      motivational systems theory. Specifically, work conditions and midlevel work goal
      processes (WGP) were examined in a questionnaire study of health care employees.
      Regarding predictions derived from the J-DCS model, the authors found full
      support for the iso-strain, partial support for the nonlinearity, and no support
      for the buffer hypothesis. Of importance, however, WGP (i.e., cognitions and
      emotions involved in the pursuit of self-set work goals) explained variance in
      job satisfaction, burnout, depression, and somatic complaints, over and above
      that of the J-DCS model. This suggests that investigation of WGP can enhance our
      understanding of employee psychological distress and well-being.

PMID- 15155035
TI  - Not all stereotypic biases are created equal: evidence for a stereotype
      disconfirming bias.
AB  - Stereotype-confirming biases are well documented in the social psychological
      literature. However, motivations to disconfirm social stereotypes may be more
      influential for unprejudiced individuals. Three experiments are presented that
      test the hypothesis that extremely unprejudiced people exhibit a bias toward
      stereotype disconfirmation. Experiment 1 investigates stereotype disconfirmation
      in information-seeking preferences. Experiments 2 and 3 explore attributional
      strategies for stereotype disconfirmation. In all experiments, unprejudiced
      participants respond in ways reflecting a motivation to disconfirm social
      stereotypes. Implications for stereotype change and stereotypic influences on
      judgment and behavior are discussed.

PMID- 15155036
TI  - Stereotype threat undermines intellectual performance by triggering a disruptive
      mental load.
AB  - Research on stereotype threat has repeatedly demonstrated that the intellectual
      performance of social groups is particularly sensitive to the situational context
      in which tests are usually administered. In the present experiment, an adaptation
      of the Raven Advanced Progressive Matrices Test was introduced as a measure of
      cognitive ability. Results showed that individuals targeted by a reputation of
      intellectual inferiority scored lower on the test than did other people. However,
      when the identical test was not presented as a measure of cognitive ability, the
      achievement gap between the target and the control group disappeared. Using heart
      rate variability indices to assess mental workload, our findings showed that the
      situational salience of a reputation of lower ability undermined intellectual
      performance by triggering a disruptive mental load. Our results indicate that
      group differences in cognitive ability scores can reflect different situational
      burdens and not necessarily actual differences in cognitive ability.

PMID- 15155037
TI  - Some evidence about character and mate selection.
AB  - The authors conducted four studies (total N = 292) about character and mate
      desirability. In Study 1, undergraduates judged stimuli for attractiveness
      physically and as a casual or longterm date. The target was described as
      faithful, having cheated but stayed with mates, or having cheated and left.
      Contrary to the hypothesis, men and women were equally affected by both kinds of
      cheaters. Study 2 replicated Study 1 with nonstudent adults. In Study 3,
      undergraduates rated a stimulus on the same attractiveness variables. This target
      had $14 million from winning a lottery or selling a dot-com company. Women, but
      not men, found the dot-com creator to be more physically attractive than the
      lottery winner. In Study 4, undergraduates rated someone who sold a cookie-making
      company or profited from a lucky real estate transaction. Both men and women
      preferred the cookie-company seller on all three measures of attractiveness.

PMID- 15155038
TI  - Political tolerance and coming to psychological closure following the September
      11, 2001, terrorist attacks: an integrative approach.
AB  - This study tested hypotheses generated from an integrative model of political
      tolerance that derived hypotheses from a number of different social psychological
      theories (e.g., appraisal tendency theory, intergroup emotion theory, and value
      protection models) to explain political tolerance following the September 11,
      2001, terrorist attacks. A national field study (N = 550) found that immediate
      post attack anger and fear had different implications for political tolerance 4
      months later. The effects of anger on political tolerance were mediated through
      moral outrage and outgroup derogation, whereas the effects of fear on political
      tolerance were mediated through personal threat, ingroup enhancement, and value
      affirmation. Value affirmation led to increased political tolerance, whereas
      moral outrage, outgroup derogation, ingroup enhancement, and personal threat led
      to decreased political tolerance. Value affirmation, moral outrage, and outgroup
      derogation also facilitated post-9/11 psychological closure and increased
      psychological closure led to greater political tolerance.

PMID- 15155039
TI  - The power in your hand: gender differences in bodily feedback from making a fist.
AB  - Men and women differ in the meaning they attribute to physical coercion and
      bodily force. Men associate bodily force with gaining power, whereas women
      associate bodily force with expressing loss of power. It is hypothesized that
      because of these associations, performing bodily forceful behavior feeds back on
      appraisals of one's power and that bodily feedback effects will mirror the gender
      differences in associations. Supporting these hypotheses, it was found that
      unobtrusively inducing behavior related to bodily force (making a fist) activated
      the concept of power in a Stroop task for both genders but that it increased hope
      for power and positive judgments of an assertively acting target for men, whereas
      it decreased hope for power and led to negative judgments of an assertively
      acting target for women.

PMID- 15155040
TI  - Effects of direct and indirect cross-group friendships on judgments of Catholics
      and Protestants in Northern Ireland: the mediating role of an anxiety-reduction
      mechanism.
AB  - Recent evidence suggests that both direct and indirect friendship with outgroup
      members (knowledge of ingroup members' friendship with outgroup members) can
      reduce prejudice toward the outgroup. Two surveys of cross-community
      relationships in Northern Ireland, using a student sample (N = 341) and a
      representative sample of the general population (N = 735), tested whether (a)
      direct and indirect friendships had generalized effects on both prejudice and
      perceived outgroup variability and (b) reduced anxiety about future encounters
      with outgroup members mediated such relationships. Structural equation modeling
      confirmed that, in both samples, direct and indirect cross-group friendships
      between Catholics and Protestants were associated with reduced prejudice toward
      the religious outgroup and increased perceived outgroup variability, via an
      anxiety-reduction mechanism. It is argued that emerging generalization hypotheses
      help to integrate both cognition and affect and interpersonal and intergroup
      approaches to contact.

PMID- 15155041
TI  - Who takes the most revenge? Individual differences in negative reciprocity norm
      endorsement.
AB  - The authors report that beliefs favoring the reciprocation of unfavorable
      treatment form a unitary factor that is distinct from beliefs favoring the
      reciprocation of favorable treatment. Individual differences in endorsement of
      this negative reciprocity norm were related to (a) beliefs that people are
      generally malevolent; (b) inclination toward anger in everyday life; (c) anger,
      disagreement, and ridicule directed toward a new acquaintance who treated
      participants unfavorably; and (d) reduced anxiety, positive emotional engagement,
      and encouragement of a new acquaintance who treated participants favorably. These
      findings suggest that individual differences in endorsement of the negative norm
      of reciprocity influence the extent of vengeance.

PMID- 15155042
TI  - A behavioral intervention to reduce child exposure to indoor air pollution:
      identifying possible target behaviors.
AB  - Indoor air pollution has been causally linked to acute lower respiratory
      infections in children younger than 5. The aim of this study was to identify
      target behaviors for a behavioral intervention to reduce child exposure to indoor
      air pollution by attempting to answer two research questions: Which behaviors are
      protective of child respiratory health in the study context? and Which behaviors
      do mothers recommend to reduce their children's exposure to indoor air pollution?
      Observations and interviews were conducted with 67 mother-child combinations. The
      authors recommend that four behavioral clusters should be considered for the main
      intervention. These are to improve stove maintenance practices, to increase the
      duration that two ventilation sources are opened while a fire is burning, to
      reduce the time that children spend close to burning fires, and to reduce the
      duration of solid fuel burning.

PMID- 15155043
TI  - Modifying pro-drug risk factors in adolescents: results from project ALERT.
AB  - The objective of this study was to evaluate the impact of a revised state-of-the
      art drug prevention program, Project ALERT, on risk factors for drug use in
      mostly rural midwestern schools and communities. Fifty-five middle schools from
      South Dakota were randomly assigned to treatment or control conditions. Treatment
      group students received 11 lessons in Grade 7 and 3 more in Grade 8. Effects for
      4276 eighth graders were assessed 18 months after baseline. Results indicate that
      Project ALERT had statistically significant effects on all the targeted risk
      factors associated with cigarette and marijuana use and more modest gains with
      the pro-alcohol risk factors. The program helped adolescents at low, moderate,
      and high risk for future use, with the effect sizes typically stronger for the
      low- and moderate-risk groups. Thus, school-based drug prevention programs can
      lower risk factors that correlate with drug use, help low- to high-risk
      adolescents, and be effective in diverse school environments.

PMID- 15155044
TI  - Violence-related outcomes of the D.A.R.E. plus project.
AB  - The objectives of this study were to examine outcomes of the Minnesota D.A.R.E.
      Plus Project on violence-related behaviors among middle school students and
      mediation analyses that test how the intervention was effective in reducing
      physical and verbal violence. Twenty-four schools were randomly assigned to the
      D.A.R.E. middle school curriculum, the D.A.R.E. Plus multicomponent intervention,
      or control. The study cohort completed a self-report questionnaire at baseline
      and two follow-ups. The results showed that boys had higher rates of violence and
      victimization than girls. The D.A.R.E. Plus program was more effective in
      preventing violence among boys than among girls. It appears that the small
      behavioral effect that D.A.R.E. Plus did demonstrate on physical and verbal
      violence among boys was entirely mediated by a decrease of norms that support
      violence, an increase in outcome expectancies about being violence-free, and an
      increase in parental consequences for fighting.

PMID- 15155045
TI  - Communicating cardiovascular disease risk due to elevated homocysteine levels:
      using the EPPM to develop print materials.
AB  - Improving the effectiveness of written information to promote compliance with
      therapeutic regimens is essential, particularly among older adults. Guiding their
      development and evaluating their effectiveness with an accepted communication
      theory or model may help. A preliminary test of written materials developed
      within the context of the Extended Parallel Process Model (EPPM) to motivate
      compliant behaviors among older adults at risk for cardiovascular disease is
      described. Participants who were not previously following the recommendations
      felt more confident in their ability to do so after reading a high-threat/high
      efficacy message. Advanced age, lower education level, an existing chronic
      illness, and a higher initial homocysteine level were factors associated with
      lower levels of perceived threat and/or fear and may have attenuated the
      effectiveness of the message. This study's results contribute to our
      understanding of the usefulness of theory-guided written materials in motivating
      compliant health behaviors. Recommendations for using this model are provided.

PMID- 15155046
TI  - Principals' perceptions and practices of school bullying prevention activities.
AB  - The purpose of this study was to examine principals' perceptions and practices
      regarding bullying prevention. A survey instrument was developed to assess
      principals' stages of change and perceived barriers regarding selected bullying
      prevention activities as well as the effectiveness of bullying prevention
      activities. Of a national random sample of 700 principals to which the survey was
      mailed, 55% responded. None of the school-based bullying prevention activities
      were being done by more than one in five schools even though principals perceived
      there to be no barriers regarding these activities. Characteristics that affected
      the offering of these activities included number of perceived barriers to
      implementing the activity, whether the principal had received violence/bullying
      prevention training, perceptions regarding the extent of bullying, and the number
      of bullying problems reported to them. The findings suggest that preprofessional
      training and continuing education are needed to educate principals regarding this
      area.

PMID- 15155047
TI  - Views and preferences of low-literate Hispanics regarding diabetes education:
      results of formative research.
AB  - Hispanics are twice as likely as non-Hispanic Whites to have diabetes and are
      also at higher risk for diabetes-related complications and poorer outcomes. The
      prevalence of diabetes is inversely related to educational status. Low literacy
      is common, especially among older Hispanics. Little literature exists on
      formative research to create diabetes education materials for this audience. Two
      focus groups assessed views and preferences for diabetes education of low
      literate, low-income, non-English-speaking urban Caribbean and Central American
      Hispanics with diabetes, as well as utility of materials developed specifically
      for this population, as part of the preliminary work for a pilot study of a
      diabetes intervention. Implications for practitioners and researchers are
      discussed.

PMID- 15155049
TI  - Frontier efficiency measurement in health care: a review of empirical techniques
      and selected applications.
AB  - Health care institutions worldwide are increasingly the subject of analyses aimed
      at defining, measuring, and improving organizational efficiency. However, despite
      the importance of efficiency measurement in health care services, it is only
      relatively recently that the more advanced econometric and mathematical
      programming frontier techniques have been applied to hospitals, nursing homes,
      health management organizations, and physician practices, among others. This
      article provides a synoptic survey of the comparatively few empirical analyses of
      frontier efficiency measurement in health care services. Both the measurement of
      efficiency in a range of health care services and the posited determinants of
      health care efficiency are examined.

PMID- 15155050
TI  - Does consumer satisfaction information matter? Evidence on member retention in
      FEHBP plans.
AB  - Taking advantage of a natural experiment, this study explores the crucial link
      between consumer satisfaction, distribution of consumer satisfaction information,
      and member retention at open enrollment. Multiple data sources, panel data
      regression analysis, and instrumental variable techniques inform how retention is
      affected by consumer satisfaction, before and after free distribution of report
      card information, controlling for market structure, consumer characteristics,
      premiums, benefits, and other plan attributes in about 250 Federal Employee
      Health Benefit Program (FEHBP) plans nationwide. Study results suggest that
      consumer satisfaction boosts member retention. Free distribution of consumer
      satisfaction information to federal employees during open enrollment is
      associated with lower member retention, which may suggest that consumers might
      have used this newly distributed information and then decided to withdraw from
      their previous plans.

PMID- 15155051
TI  - The effect of insurance status on travel time for rural Medicare patients.
AB  - Managed care has been hypothesized to increase patient travel by directing
      patients toward network providers. The purpose of this study is to measure the
      effect of Medicare HMO enrollment on hospital travel time in rural areas.
      Hospital travel times were determined for 85,586 inpatient discharges among rural
      Pennsylvania residents admitted to Pennsylvania hospitals in 1998. Medicare HMO
      enrollees traveled up to 10.2 minutes further for acute care than Medicare fee
      for-service patients (39 versus 29 minutes). Medicare HMO enrollees were 50
      percent more likely to travel outside their own counties and 70 percent more
      likely to travel to urban areas for acute care. The distance premium associated
      with HMO enrollment was largest in counties with the lowest managed care
      penetration.

PMID- 15155052
TI  - Relative risk of postpartum complications in the Ohio Medicaid population:
      vaginal versus cesarean delivery.
AB  - The objective of this study was to estimate the relative risk of postpartum
      complication by type of delivery among Ohio Medicaid beneficiaries. The study
      uses the linked Medicaid and Ohio birth certificate data for births occurring
      from July 1991 through April 1996 (N = 168,736). The results indicate that the
      incidence of major puerperal infection, thromboembolic events, anesthetic
      complications, and obstetrical surgical wound infection was higher among women
      undergoing a C-section as compared to those with vaginal delivery, even after
      limiting the analysis to elective cesarean deliveries and uncomplicated vaginal
      deliveries. On the other hand, women with C-sections were less likely to
      experience obstetrical trauma, and results on postpartum hemorrhage were
      inconclusive. Aside from obstetrical trauma, the relative risk of postpartum
      complications remains significantly higher among women undergoing C-section.
      These findings are of particular relevance in light of the substantial proportion
      of repeat C-sections performed on an elective basis.

PMID- 15155053
TI  - The rate and cost of hospital readmissions for preventable conditions.
AB  - The study estimates the rate and cost of preventable readmissions within 6 months
      after a first preventable admission, by age-group, and by payer and race within
      age-group. The descriptive results are contrasted with several hypotheses. The
      hospital discharge data are for residents of New York, Pennsylvania, Tennessee,
      and Wisconsin in 1999, from files of the Healthcare Cost and Utilization Project
      of the Agency for Healthcare Research and Quality. About 19 percent of persons
      with an initial preventable admission had at least one preventable readmission
      rate within 6 months. Hospital cost for preventable readmissions during 6 months
      was about 730 million US dollars. There were substantial differences in
      readmission rates by payer group and by race. Some evidence suggests that
      preventable readmissions may partly reflect complexity of underlying problems.
      Interventions to reduce cost might focus on identifying high-risk patients before
      discharge and devising new approaches to follow-up.

PMID- 15155057
TI  - Comment on "Disruption in the inhibitory architecture of the cell minicolumn:
      implications for autism".
AB  - Narrow neural columns have been suggested to be a neuroanatomical abnormality in
      autism. A previous hypothetical explanation, an unbalance between excitatory and
      inhibitory lateral feedback in the neocortex, has been found to be difficult to
      reconcile with the relatively high comorbidity of autism with epilepsy. Two
      alternative explanations are discussed, an early low capacity for producing
      serotonin, documented in autism, and insufficient production of nitric oxide. An
      early low level of serotonin has in animal experiments caused narrow neural
      columns. Insufficient nitric oxide is known from neural network theory to cause
      narrow neural columns.

PMID- 15155058
TI  - The NMDA receptor gating machine: lessons from single channels.
AB  - The slow component of the excitatory postsynaptic current in the central nervous
      system is generated by the activity of NMDA receptors. The activation properties
      of this class of glutamate receptor determine key features of the synaptic
      response and have important consequences for synaptic plasticity and cell
      physiology. NMDA receptor activation is complex and involves ligand binding,
      protein conformational changes, and channel blockade. Recently, two groups have
      proposed state models that encapsulate the essential features of NMDA receptor
      gating conformational changes. These models provide insight into the NMDA
      receptor as a molecular machine and should help us understand and manipulate NMDA
      receptor mediated synaptic function and pathologies.

PMID- 15155059
TI  - Imbalance of glial-neuronal interaction in synapses: a possible mechanism of the
      pathophysiology of bipolar disorder.
AB  - There is a wave of new information suggesting that glia, especially astrocytes,
      are intimately involved in the active control of neuronal activity and synaptic
      transmission. Synaptically associated astrocytes should be viewed as integral
      modulatory elements of tripartite synapses consisting of the presynapse, the
      postsynapse, and the glial element (astrocytes). Smit and coworkers proposed a
      model of a cholinergic tripartite synapse based on the identification of a glial
      derived binding protein (BP) that is secreted into the synapse and binds free
      acetylcholine (ACh), thus reducing the levels of ACh available for stimulating
      the postsynapse. Here the author proposes an explanatory model of the
      pathophysiology of bipolar disorder focusing on the possible dynamics in
      cholinergic tripartite synapses. The hypothesis is that an imbalance between
      neurotransmitters and glial BPs in the synaptic cleft is determined by glia. If
      glial BPs are overexpressed, synaptic transmission is suppressed because of
      reduced levels of bioavailable neurotransmitters. This state could cause a
      depression on the behavioral level. In contrast, if glial BPs are underexpressed,
      the excess of neurotransmitters in the cleft leads to an overbalanced state of
      synaptic information transmission. This state could cause manic behavior. Under
      certain conditions, underbalanced and overbalanced synapses at different
      locations in the same brain could disturb brain function in parallel causing a
      mixed episode of bipolar disorder. If glial BPs and mutations in genes expressing
      glial BPs in the various synapses of the brain are identified, this hypothesis
      can be experimentally tested.

PMID- 15155060
TI  - The integrated nature of motor cortical function.
AB  - Recent studies on the functional organization and operational principles of motor
      cortical function, taken together, strongly support the notion that the motor
      cortex controls the muscle activities subserving movements in an integrated
      manner. For example, during pointing the shoulder, elbow and wrist muscles appear
      to be controlled as a coupled functional system, rather than individually and
      separately. The pattern of intrinsic connections between motor cortical points is
      likely part of the explanation of this operational principle. So too is the
      manner in which muscles and muscle synergies are represented in the motor cortex.
      However, selection of movement-related muscle synergies is likely a dynamic
      process involving the functional linking of a variety of motor cortical points,
      rather than the selection of fixed patterns embedded in the motor cortical
      circuitry. One of the mechanisms that may be involved in the functional linking
      of motor cortical points is disinhibition. Thus, motor cortical points are
      recruited into action by selected excitation as well as by selected release from
      inhibition. The incoordination of limb movements in patients after a stroke may
      be understood, at least in part, as a disruption of the connections between motor
      cortical points and of the neural mechanisms involved in their functional
      linking.

PMID- 15155061
TI  - The amygdala and persistent pain.
AB  - A reciprocal relationship exists between persistent pain and negative affective
      states such as fear, anxiety, and depression. Accumulating evidence points to the
      amygdala as an important site of such interaction. Whereas a key role of the
      amygdala in the neuronal mechanisms of emotionality and affective disorders has
      been well established, the concept of the amygdala as an important contributor to
      pain and its emotional component is still emerging. This article will review and
      discuss evidence from anatomical, neuroimaging, behavioral, electrophysiological,
      pharmacological, and biochemical data that implicate the amygdala in pain
      modulation and emotional responses to pain. The latero-capsular division of the
      central nucleus of the amygdala is now defined as the "nociceptive amygdala" and
      integrates nociceptive information with poly-modal information about the internal
      and external bodily environment. Dependent on environmental conditions and
      affective states, the amygdala appears to play a dual facilitatory and inhibitory
      role in the modulation of pain behavior and nociceptive processing at different
      levels of the pain neuraxis. Only recently, electrophysiological,
      pharmacological, and biochemical neuroplastic changes were shown in the
      nociceptive amygdala in persistent pain. It is conceivable, however, that
      amygdala plasticity plays an important role in emotional pain behavior and its
      modulation by affective state.

PMID- 15155062
TI  - Brain circuits regulating energy homeostasis.
AB  - For decades, increasingly sophisticated methods have been designed to address the
      problem of the involvement of the brain in the physiology of energy homeostasis
      and the pathogenesis of obesity. A vast number of experimental observations have
      been made from novel genetic and physiologic approaches that allowed the
      identification of metabolic hormones and their relationship to key peptidergic
      systems in the brain. Although the central integration of afferent signals
      reflecting acute and chronic energy requirements is becoming clearer, the
      blueprint of the central regulation of energy expenditure is not known. This
      review offers a look at central neuronal circuitries that are implicated in
      metabolism regulation and strongly suggests that without a blueprint, attempts to
      intervene and control energy balance will remain futile.

PMID- 15155063
TI  - Cerebellar control of balance and locomotion.
AB  - The cerebellum is important for movement control and plays a particularly crucial
      role in balance and locomotion. As such, one of the most characteristic signs of
      cerebellar damage is walking ataxia. It is not known how the cerebellum normally
      contributes to walking, although recent work suggests that it plays a role in the
      generation of appropriate patterns of limb movements, dynamic regulation of
      balance, and adaptation of posture and locomotion through practice. The purpose
      of this review is to examine mechanisms of cerebellar control of balance and
      locomotion, emphasizing studies of humans and other animals. Implications for
      rehabilitation are also considered.

PMID- 15155064
TI  - The neural substrates of reward processing in humans: the modern role of FMRI.
AB  - Experimental work in animals has identified numerous neural structures involved
      in reward processing and reward-dependent learning. Until recently, this work
      provided the primary basis for speculations about the neural substrates of human
      reward processing. The widespread use of neuroimaging technology has changed this
      situation dramatically over the past decade through the use of PET and fMRI.
      Here, the authors focus on the role played by fMRI studies, where recent work has
      replicated the animal results in human subjects and has extended the view of
      putative reward-processing neural structures. In particular, fMRI work has
      identified a set of reward-related brain structures including the orbitofrontal
      cortex, amygdala, ventral striatum, and medial prefrontal cortex. Moreover, the
      human experiments have probed the dependence of human reward responses on learned
      expectations, context, timing, and the reward dimension. Current experiments aim
      to assess the function of human reward-processing structures to determine how
      they allow us to predict, assess, and act in response to rewards. The authors
      review current accomplishments in the study of human reward processing and focus
      their discussion on explanations directed particularly at the role played by the
      ventral striatum. They discuss how these findings may contribute to a better
      understanding of deficits associated with Parkinson's disease.

PMID- 15155065
TI  - Racial differences in perceived discrimination in a community population of older
      blacks and whites.
AB  - OBJECTIVES: To examine the prevalence of perceived discrimination in an older
      biracial population and to examine its correlation with depressive symptoms.
      METHODS: The sample consisted of 2,652 Blacks and 1,630 Whites, 68 years old and
      older, from the Chicago Health and Aging Project (CHAP). Perceived discrimination
      was measured with a nine-item scale developed by Williams, Yu, Jackson, and
      Anderson (1997). RESULTS: A factor analysis of the discrimination scale revealed
      two subscales, unfair treatment and personal rejection. Blacks scored higher on
      both subscales as compared with Whites. In linear regression models, race was
      significantly associated with higher levels of unfair treatment and personal
      rejection, controlling for demographic variables and socioeconomic status (SES).
      Each subscale was also positively related to depressive symptoms, and these
      effects did not vary by race. DISCUSSION: These findings suggest that older
      Blacks perceive more discrimination than do older Whites. This may have important
      implications for health differences between older Blacks and Whites.

PMID- 15155066
TI  - Can the family still cope? Social support and health as determinants of nursing
      home use in the older Mexican-origin population.
AB  - OBJECTIVES: This article examines the impact of disability, cognitive status, and
      social support on nursing home use in a sample of older Mexican Americans.
      METHOD: We used four waves of the Hispanic Established Populations for
      Epidemiologic Studies of the Elderly (H-EPESE), a longitudinal study of 3,050
      older Mexican Americans living in the Southwest initially contacted in 1993 to
      1994. RESULTS: The findings reveal that advanced age, being a man, activities of
      daily living disability, and cognitive impairment are strong predictors of
      institutionalization and death. Living with family, arriving in the United States
      in late life, and access to social support independently decreased the
      probability of dying in a nursing home. DISCUSSION: Although it is clear that
      adequate social support can make it possible for an impaired older person to
      remain in the community serious impairment can eventually overwhelm even a
      supportive network and result in the institutionalization of an impaired older
      person.

PMID- 15155067
TI  - Religion and functional health among the elderly: is there a relationship and is
      it constant?
AB  - OBJECTIVES: Religion significantly influences a variety of health outcomes,
      especially among the elderly. Few studies have examined how the relationship may
      differ by age within this age group. It is possible that increasing levels of
      religiosity within the elderly, or other age-related differences, may strengthen
      the influence of religion on functional limitations. METHOD: This study used the
      Assets and Health Dynamics Among the Oldest Old Survey, a nationally
      representative, longitudinal data set, to estimate the effects of religious
      attendance and salience on functional ability. RESULTS: More frequent attendance
      is associated with fewer functional limitations, whereas higher levels of
      salience are associated with more limitations. No significant age interactions
      were found. DISCUSSION: Attendance and salience predict the number of functional
      limitations in the elderly but in different directions. These effects tend to be
      stable within the elderly population, indicating that further age divisions may
      not be necessary when examining this relationship in future studies.

PMID- 15155068
TI  - Predictors of time to nursing home placement in White and African American
      individuals with dementia.
AB  - OBJECTIVE: This study examined the influence of racial group identification on
      nursing home placement (NHP) for individuals with dementia before and after
      adjusting for the possible mediating effects of the caregiving context as defined
      by stress-process variables in 215 caregiver/care recipient dyads. METHOD:
      Demographics, problem behaviors, self-care impairment, and caregiver appraisal,
      social support, psychological well-being, and coping were used to prospectively
      predict Time to NHP. RESULTS: Race was a significant predictor of NHP with
      African American care recipients placed significantly slower than White care
      recipients. Race remained a significant predictor of Time to NHP after
      controlling for other variables that showed independent association with Time to
      NHP and stress-process variables. DISCUSSION: Findings suggest that stress
      process variables are critical factors in Time to NHP; however, these variables
      do not explain fully the difference in Time to NHP seen in White and African
      American care recipients.

PMID- 15155069
TI  - The effect of spousal mental and physical health on husbands' and wives'
      depressive symptoms, among older adults: longitudinal evidence from the Health
      and Retirement Survey.
AB  - OBJECTIVE: To estimate the effect of spousal depressive symptoms and physical
      health on respondents' depressive symptoms in a national sample of older married
      couples. METHOD: We used data on 5,035 respondent husbands and wives from the
      1992 and 1994 waves of the Health and Retirement Survey. Multivariate regression
      models were estimated to examine the impact of spousal depressive symptoms and
      physical health on respondents' depressive symptoms. RESULTS: Adjusting for
      respondent mental and physical health and sociodemographic traits, having a
      spouse with more depressive symptoms was associated with significantly higher
      follow-up depressive symptoms in the respondent (p < .001). Controlling for
      spousal depressive symptoms, a decline in the spouses' physical health was
      associated with a significant reduction in respondent depressive symptoms (p <
      .05). DISCUSSION: Our findings suggest that health care providers treating older
      adults should be sensitive to the possibility that spouses may be affected when
      clients suffer poor mental or physical health.

PMID- 15155070
TI  - Barriers to eligibility and enrollment among older women in a clinical trial on
      osteoporosis: effects of ethnicity and SES.
AB  - OBJECTIVES: The study examined whether ethnicity or socioeconomic status
      influenced a group's ability to meet eligibility criteria and willingness to
      enroll. METHOD: The eligibility and enrollment status of 904 women aged 65 years
      and older who responded to recruitment efforts of an estrogen and osteoporosis
      clinical trial were analyzed. RESULTS: Among women screened, 59% were White, 27%
      African Americans, and 14% Hispanics; average age was 75 years; 57.6% were
      eligible, of which 32% enrolled. High-income area residents were more likely to
      be eligible than low-income residents. African Americans were less likely to be
      eligible for medical reasons than non-African Americans. Eligible Hispanics were
      more likely to be enrolled than non-Hispanics. African Americans were equally
      willing to enroll as Whites. Minority residents of low-income areas were more
      likely to enroll than minority residents of high-income areas. DISCUSSION:
      Recruitment efforts should address barriers to eligibility and barriers to
      willingness to enroll.

PMID- 15155071
TI  - [Inducible expression of reconstructed human caspase-6 gene in Hela cells].
AB  - AIM: To observe the pro-apoptotic effect of RCasp-6 gene in Hela cells. METHODS:
      RCasp-6 gene was amplified by PCR and cloned into the pIND vector. Hela cells
      were transfected with pIND-RCasp-6 and then inducced with ecdyson analogue.
      Expression of target gene was detected by immunocytochemical staining. Changes of
      the morphology and growth of Hela cells subjected to transfection of target gene
      were observed by HE staining and viable cell counting. RESULTS: RCasp-6 gene was
      cloned by PCR and its eukaryotic expression vector was successfully
      reconstructed. Expression of RCasp-6 gene in the transfected Hela cells leads to
      the morphological changes of the cells. Many of the transfected Hela cells shrunk
      and some cells were died. CONCLUSION: The expression of reconstructed human
      caspase-6 gene can efficiently accelerate death of Hela cells.

PMID- 15155072
TI  - [Construction of GPI-CTLA4Ig chimeric molecule and its expression on CHO-dhfr(-)
      cells].
AB  - AIM: To develop a novel immunosuppressant GPI-CTLAIg modified by glycosyl
      phosphatidylinositol(GPI). METHODS: GPI-modified CTLAIg was produced by linking
      up of CTLA4Ig with GPI-modification signal sequences from decay-accelerating
      factor (DAF). Chimeric molecule GPI-CTLA4Ig gene was cloned into eukaryotic
      expression vector pCI-dhfr. Using lipofectine-mediated gene transfer technique,
      pCI-GPI-CTLA4Ig was transfected into CHO-dhfr(-) cells, and the transfectants
      were screened by methotrexate (MTX). Expression of the recombinant protein was
      assessed by RT-PCR, ELISA, cell immunofluorescence staining and Western blot, and
      the purification of expressed protein was performed by protein A affinity
      chromatography. RESULTS: The chimeric molecule GPI-CTLA4Ig has been constructed
      and stablely expressed on CHO-dhfr(-) cells. CONCLUSION: GPI-modified CTLAIg will
      may be used as novel immunosuppressant for suppressing reaction in graft
      rejection.

PMID- 15155073
TI  - [Expression of amino terminal of nucleoprotein and glycoprotein G2 of Hantaan
      virus in insect cells in the form of fusion protein].
AB  - AIM: To express the glycoprotein G2 and amino terminal of nucleoprotein (NP) of
      Hantaan virus in Bac-to-Bac baculovirus expression system in the form of fusion
      protein. METHODS: The recombinant baculovirus expression vector pFBDHTa-G2S 0.7
      was constructed. The chimeric gene was inserted into bacmid in E.coli DH10Bac
      with the help of Tn7 transposition system. Then the recombinant baculovirus was
      screened and the fusion protein was expressed in insect cells. The expression
      product was detected by ELISA, immunofluorescence assay and Western blot
      analysis. RESULTS: The recombinant baculovirus containing the chimeric gene G2S
      0.7 had been constructed successfully and the fusion protein could be expressed
      in insect cells. The expressed protein could be recognized by the Hantaan virus
      NP-specific mAb and glycoprotein G2-specific mAb. CONCLUSION: The successful
      expression of fusion protein G2S 0.7 with biological activity in insect cells
      lays the foundation for further research on its immunological characteristic.

PMID- 15155074
TI  - [The expression and localization of p27(KIP1)-GFP fusion gene in hepatocellular
      carcinoma cell lines].
AB  - AIM: To study the expression and localization of p27(KIP1)-GFP fusion protein in
      hepatocellular carcinoma cell line HCC-9204. METHODS: According to the encoded
      sequence of human p27(KIP1) gene, stop codon TAA located at 3' terminus of
      p27(KIP1) gene was mutated into TGT by PCR and fused with GFP gene. Then the
      p27(KIP1)-GFP cDNA was transfected into HCC-9204 cells. The expression of
      p27(KIP1)-GFP fusion protein was observed under fluorecence microscope. RESULTS:
      DNA sequencing demonstrated that difference between p27(KIP1) gene and that in
      Genbank was only one nucleoside and the encoded protein sequence is identical.
      The observation under fluorecence microscope reporced showed that fluorochrome
      was spread in entire HCC-9204 cells transfected with GFP gene, whereas green
      fluorescence was seen mainly in the nucleus of HCC-9204 cells transfected with
      p27(KIP1)-GFP gene. CONCLUSION: The human p27(KIP1)-GFP fusion protein could be
      expressed in HCC-9204 cells and located in the nucleus, which is similar to the
      expression of p27(KIP1) gene.

PMID- 15155075
TI  - [Detection of C5a receptor expressions on human epiretinal membranes and cultured
      RPE cells by immunohistochemical staining].
AB  - AIM: To observe the expression and distribution of C5a receptor(C5aR) on
      epiretinal membranes (ERM) tissue from patients with proliferative retreous body
      retina (PVR) lesion and cultured retinal pigmentary epithelial (RPE) cells.
      METHODS: The C5aR expressions on ERM tissue and cultured RPE cells were detected
      by ABC immunohistochemical staining with mouse anti-human C5aR mcAbs. RESULTS:
      Expression of C5aR was found in ERM tissue and on cultured RPE cells as well as
      macrophages. CONCLUSION: As a pro-inflammatory factor, binding of C5a to C5aR on
      RPE cells may play an important role in the development of PVR.

PMID- 15155076
TI  - [Construction of VEGF eukaryotic expression vector and its expression in
      endothelial cells and cardiac myocytes in-vitro].
AB  - AIM: To study the feasibility of VEGF165 gene transfection to endothelial cells
      and cardiac myocytes in-vitro. METHODS: The VEGF165 DNA fragment was inserted
      into a green fluorescent protein fusion vector, which was then transfected into
      endothelial cells and cardiac myocytes with lipofectamine. RESULTS: The
      endothelial cells and cardiac myocytes were successfully transfected with pIRES2
      EGFP-hVEGF165 gene, which was confirmed by fluoroscopy and immunohistochemistry.
      CONCLUSION: VEGF can be expressed stably in the endothelial cells and cardiac
      myocytes, which might be useful for the gene therapy of myocardial ischemia.

PMID- 15155077
TI  - [Construction and expression of eukaryotic expression plasmid pcDNA3.1/hIL-18].
AB  - AIM: To construct an eukaryotic expression plasmid pcDNA3.1/hIL-18 and express it
      in mammalian cells. METHODS: cDNA encoding mature hIL-18 was cleavaged by enzyme
      digestion from mesomeric clone vector pGEM-T/hIL-18 and inserted into an
      eukaryotic expression plasmid pcDNA3.1 to construct a recombinant expression
      plasmid pcDNA3.1/hIL-18. Then the constructed plasmid was transfected into COS-7
      and Rlc310 cells by liposome-mediated gene transfer method. hIL-18 expressed in
      transfected COS-7 and Rlc310 cells was detected by immunohistochemical staining
      and level of hIL-18 mRNA in transfected Rlc310 cells was assayed by RT-PCR.
      RESULTS: A recombinant eukaryotic expression plasmid pcDNA3.1/hIL-18 was
      successfully constructed and expressed transiently in COS-7 cells and stably in
      Rlc310 cells. CONCLUSION: The construction and expression of pcDNA3.1/hIL-18 have
      been achieved successfully, which lays a foundation for further research on anti
      tumor effect of IL-18.

PMID- 15155078
TI  - [Construction of human integrin beta3 subunit eukaryotic expression vector and
      efficient surface expression of integrin alphaIIbbeta3].
AB  - AIM: To establish efficient surface expression of Homo sapiens integrin
      alphaIIbbeta3 in beta3-integrin-deficient and HV-insusceptible CHO cells, so as
      to lay the foundation for the further study of cellular entry of hantavirus
      mediated by beta3 integrins. METHODS: Eukaryotic expression vector pcDNA3.1-beta3
      harboring ORF region of human integrin beta3 subunit cDNA was constructed, then
      pcDNA3.1-beta3 and eukaryotic expression vector pBJ1-alphaIIb containing human
      integrin alphaIIb subunit cDNA were transfected into CHO cells alone or together.
      The expression of exogenous genes were analyzed by indirect immunofluorescence
      assay (IFA). RESULTS: The eukaryotic expression vector pcDNA3.1-beta3 was
      constructed successfully. IFA examination showed that surface expression of
      integrin alphaIIb beta3 was highly effective in cotransfection group, while
      surface expression was weak on CHO cells transfected with pcDNA3.1-beta3
      alone,and no effective surface expression was found in pBJ1-alphaIIb-transfected
      group. CONCLUSION: Efficient surface expression of integrin alphaIIb beta3
      requires expression of both subunits.

PMID- 15155079
TI  - [Expression and significance of enkephalin and dopamine in experimental rat
      cerebral concussion tissue].
AB  - AIM: To explore the expression and significance of enkephalin and dopamine in rat
      cerebral concussion tissue. METHODS: 80 Wistar male rats were used to make animal
      model of cerebral concussion, which were sacrificed on 1,3,7,14 and 30 days after
      postconcussion and the brain tissues were taken out. The expression patterns of
      enkephalin and dopamine were studied in the course of cerebral concussion by
      immunohistochemical staining. RESULTS: The clinical manifestation with typical
      cerebral concussion character was seen in rat group with 100 g body weight. The
      mainly pathologic changes were cerebral vascular constriction and dilatation,
      congestion and edema of cerebral tissue, and neuronal degeneration and necrosis.
      Expression of enkephalin was increased on day 1 after injury and the enkephalin
      positive area was in the plasma of endothelial cells in cerebral cortex,
      hippocamp and cerebellum. The expression of enkephalin reached the peak on day 7
      after injury, and the positive area was also seen in the plasma of neurons in
      cerebral cortex, hippocamp and cerebellum. From 14 days after injury, the
      expression of enkephalin decreased gradually, but until 30 days after injury it
      was still higher than that of controls. Expression of dopamine increased in 7
      days after injury and the positive area was seen in the plasma of endothelial
      cells and in the vessel wall in cerebral cortex, hippocamp, thalamus and
      cerebellum, and had no notable changes at other time points. CONCLUSION: The
      mainly pathologic changes after cerebral concussion were blood circulatory
      disorder and denaturation and necrosis of parenchymal cells. Enkephalin and
      dopamine may participate in the pathophysiological course of cerebral injury
      after cerebral concussion, and play an important role in the blood vessel injury,
      regulation of blood-brain barrier and the denaturation and necrosis of nerve
      cells.

PMID- 15155080
TI  - [Effects of polymyxin B on LPS-induced activation of NF-kappaB in pulmonary
      alveolar macrophages].
AB  - AIM: To observe effects of polymyxin B (PMB) on LPS-induced activation of NF
      kappaB of pulmonary alveolar macrophages(PAMs) and explore the possible anti
      inflammation efficiency of PMB. METHODS: Rat PAMs were isolated and cultured. The
      PAMs were divided into 3 groups, namely, normal control group (PAMs+normal
      solution), LPS stimulation group (PAMs+10 mg/L LPS) and PMB interference
      group(after PMB treatment for 30 min, using LPS stimulation). The PAMs were fixed
      respectively at 0,15,30,60,120 and 240 min after stimulation. Nucleoprotein was
      extracted from cultured PAMs and culture supernatant of the PAMs was collected.
      The expression of IKK-beta mRNA in the PAMs, NF-kappaB activity in PMB
      nucleoprotein extractive, TNF-alpha content in culture supernatant of the PAMs
      were detected by in situ hybridization (ISN), electrophoretic mobility shift
      assay (EMSA) and ELISA, respectively. RESULTS: IKK-beta mRNA level in LPS group
      increased at 15 min, reached the peak at 30 min, while IkappaB-alpha level turned
      out contrary to IKK-beta mRNA level. The peak of NF-kappaB activity appeared at
      60-120 min after stimulation was significantly higher than those of pre
      stimulation and normal control group (P<0.01). In PMA interference group, NF
      kappaB activity and TNF-alpha level were markedly lower than those in LPS
      stimulation group (P<0.01). The lowest level of IkappaB-alpha was notably higher
      than that in LPS stimulation group, while the peak of IKK-beta mRNA was obviously
      lower than that in LPS stimulation group (P<0.01). CONCLUSION: LPS can induce IKK
      beta and NF-kappaB activation, IkappaB-alpha degradation, accelerate TNF-alpha
      release, but PMB can counteract those effects induced by LPS stimulation.

PMID- 15155081
TI  - [Protective immunoresponse to CVB3 induced by gene immunization with pcDNA3-VP1].
AB  - AIM: To induce Coxsackie virus B type 3 (CVB3)-specific immune response by using
      a DNA vaccine containing CVB3-VP1 and to observe its protection against CVB3
      challenge. METHODS: The gene coding for VP1 was obtained by RT-PCR and then was
      cloned into plasmid pcDNA3 to construct pcDNA3-VP1. In-vitro expression of VP1
      was performed by transfection of pcDNA3-VP1 into Hela cells. Expressed product
      was detected by ELISA. BALB/c mice were immunized intramuscularly with 50 microg
      DNA three times, and challenged by 5xLD(50) CVB3 four weeks after the last
      immunization. RESULTS: pcDNA3-VP1 had been constructed and the expression product
      was detected in the culture supernatant of Hela cells 24 hours after
      transfection. CVB3-specific IgM and IgG elicited in the mice immunized with
      pcDNA3-VP1 were significantly higher than those in the control mice immunized
      with pcDNA3. Specific proliferation of the splenic lymphocytes and activity of
      CVB3-specific CTLs from the pcDNA3-VP1 immunized mice were much stronger than
      those in the controls. pcDNA3-VP1 could protect 33.3% mice from lethal CVB3
      challenge, while control mice only survived 6.7 days. Infiltration of
      inflammatory cells or unusual proliferation of connective tissue, indicating
      ongoing myocarditis or fibrosis, were not found in pcDNA3-VP1 immunized mice, but
      did exist in control mice. CONCLUSION: Intramuscular immunization with pcDNA3-VP1
      may be a promising approach against CVB3 infection.

PMID- 15155082
TI  - [Enhancement of HBV gene-induced specific cell-mediated immunoresponse by C3d
      P28].
AB  - AIM: To investigate whether P28 derived from complement C3d can enhance the cell
      mediated immunoresponse to HBV-preS2/S induced by direct injection of naked
      plasmid DNA containing four tandem repeats of C3d-P28 gene and HBV-preS2/S gene
      existed in fusion form. METHODS: Four copies of gene coding for C3d-P28,
      amplified by PCR and cut by restriction endonucleases digestion, were subcloned
      into a eukaryotic expression vector pVAON33 to construct pVAON33-P28.4. HBV
      preS2/S gene was then introduced into the pVAON33 and pVAON33-P28.4 respectively
      to form pVAON33-S2/S and pVAON33-S2/S-P28.4. The recombinant plasmids were
      identified by PCR and restriction endonucleases digestion as well as DNA
      sequencing. BALB/c mice were immunized i.m. three times at 3 weeks' intervals
      with 100 microg of pVAON33-S2/S DNA, pVAON33-S2/S-P28.4 and mock DNA,
      respectively. Splenocytes from immunized mice were stimulated by HBsAg and then
      harvested to analyze the specific lymphocytic proliferative response and CTL
      cytotoxic activity by (3)H-TdR incorporation assay and isotopic release analysis,
      respectively. RESULTS: Specific lymphocytic proliferation and CTL cytotoxic
      activity against HBV-preS2/S were observed in mice immunized by both pVAON33-S2/S
      and pVAON33-S2/S-P28.4 in dose-dependent form. Specific lymphocytic proliferation
      and CTL response in mice immunized by pVAON33-S2/S-P28.4 were markedly stronger
      than those in mice immunized by pVAON33-S2/S. CONCLUSION: A C3d-P28 can enhance
      the cell-mediated immunoresponse induced by HBV-preS2/S gene immunization.

PMID- 15155083
TI  - [Expression of human KIR2DL1-Ig fusion protein in COS-7 cells].
AB  - AIM: To express, purify and identify the KIR2DL1-IgG Fc fusion protein. METHODS:
      Extracellular region of KIR2DL1 cDNA was amplified by RT-PCR from peripheral
      blood mononuclear cells, and cloned this fragment into fusion expression vector
      CD5lnegl. The recombinant vector CD5lnegl-KIR2DL1 was obtained after restriction
      endonuclease digestion and sequencing. COS-7 cells were transfected with this
      eukaryotic expression vector CD5lnegl-KIR2DL1 constructed in our Laboratory
      through DEAE-dextran/chloroquine method. The expressed KIR2DL1-IgGFc fusion
      protein in COS-7 cell culture surpernatant was identified by ELISA with mAb EB6
      and HRP-anti-hIgFc mAb and Western blot. RESULTS: Restriction endonuclease
      digestion and sequencing indicated that the CD5lnegl-KIR2DL1 had been constructed
      successfully. The fusion protein could be detected by ELISA in COS-7 cell culture
      surpernatant. Western blot analysis also showed that the fusion protein could
      react to both EB6 and anti-hIgFc mAb. There was only one specific band at the
      position of the relative molecular mass (M(r)) 73 000, and it was equivalent to
      the expected value. CONCLUSION: KIR2DL1-IgG Fc fusion protein expressed in COS-7
      cells successfully and the protein can mimic the natural KIR2DL1 protein and is
      used as a potential tool in the recognition of its ligands.

PMID- 15155084
TI  - [Study on the preparing of polyclonal antibodies against plant-selected maker
      gene hpt expression protein by DNA immunization].
AB  - AIM: To prepare the polyclonal antibodies (pAbs) against HPT, a kind of plant
      selected maker gene encoding protein, by DNA immunization technique and explore
      the influencing factors for this gene immunization. METHODS: The coding sequence
      of hpt was cloned into eukaryotic expression vector pCDNA3. The sequence of the
      plasmid pCDNA3-HPT was demonstrated by restricting enzyme digestion analysis and
      DNA sequencing. The sequence-correct recombinant plasmids were purified and used
      to immunize BALB/c mice. The titer and specificity of antisera were detected by
      ELISA and Western blot, respecitively. RESULTS: No pAb against HPT was detected
      following three immunization with hpt genes. Then mice were divided into three
      groups when the forth booster immunization was carried out: 1st group
      (immunization with the endotoxin-free recombinant plasmids), 2nd group
      (immunization with (His)(6)-HPT fusion protein expressed in E.coli) and 3rd group
      (immunization with the same plasmids as before mentioned). As a result, the pAb
      titer of the 1st group mice increased to 1:200, and the that of 2nd group was up
      to 1:2 000. Yet the 3rd group detected no anti-HPT antibody. Western blot
      analysis had proved that antisera of the first two groups could produce specific
      binding reaction to the purified GST-HPT, (His)(6)-HPT protein and their
      expressed product (bacterial protein). CONCLUSION: We have got successfully the
      specific pAb against HPT by DNA immunization, but its titer is yet
      unsatisfactory, inferring that the character of the hpt gene self and its
      expression level may play an important role. In order to raise level of serum
      antibody prepared by DNA immunization, the farther study on various influencing
      factors still need to be performed.

PMID- 15155086
TI  - [Study of antibody enzyme with acetylcholonesteraseactivity].
AB  - AIM: To study anti-idiotype antibody(AId Ab)directed at mAb 3F3 Fab idiotypic
      determinant with acetylcholinesteras(AchE) activity. METHODS: Anti-AchE mAb
      3F3(IgG1) was digested by papain to prepare its Fab fragments. And then the Fab
      fragments were purified through Ach- and SPA-Sepharose 4B columns respectively.
      The BALB/c mice were immunized by using purified Fab fragments as immunogen to
      prepare AId Abs against the Fab fragmrnts. Catalytic activity of the AId Abs was
      detected by ELISA. RESULTS: The purified mAb 3F3 Fab fragments were acquired by
      papain digestion and affinity chromatograpy successively. Enzyme catalysis ELISA
      detection showed that AId Abs to the Fab fragments had activity of AchE.
      CONCLUSION: An AId Ab to mAb 3F3 Fab fragments has been prepared successfully,
      which opens up a novel way for treatment of pesticides poisoning.

PMID- 15155085
TI  - [Development of an anti-rTNF-alpha chimeric antibody].
AB  - AIM: To develop an human-mouse chimeric antibody against rTNF-alpha. METHODS:
      Expression vector of human-mouse chimeric antibody CZ12 gene was constructed by
      using VL and VH genes of mAb Z12 with neutralizing activity, and then COS7 cells
      were transfected. Supernatant containing CZ12 was detected by RT-PCR, ELISA,
      Western blot and in-vitro neutralization assay, respectively. RESULTS: The RT-PCR
      analysis showed that there was the transcription of human-mouse chimeric antibody
      mRNA in the transfected COS7 cells. ELISA and Western blot detection showed that
      the CZ12 could recognize specifically TNF-alpha. The in-vitro neutralization
      assay proved that CZ12 could neutralize the cytoxicity of TNF-alpha to L929
      cells. CONCLUSION: human-mouse chimeric antibody CZ12 with neutralizing activity
      was successfully expressed in eukaryotic cells.

PMID- 15155087
TI  - [Study of the inhibiting effect of anti-NKG2D polyclonal antibody on
      cytotoxicities of NK and LAK cells].
AB  - AIM: To investigate the effect of anti NKG2D polyclonal antibody(pAb) on
      cytotoxicities of NK and LAK cells. METHODS: Peripheral blood mononuclear
      cells(PBMCs) were separated by centrifugation on Ficoll-Hypaque gradients. LAK
      cells were induced from PBMCs by PHA (10 mg/L) and rhIL-2 (1x10(6)U/L). Then NK
      cells were sorted by flow cytometry(FCM). The cytotoxicities of NK and LAK cells
      were analyzed by MTT colorimetry after NKG2D molecule on NK and LAK cells were
      blocked with anti-NKG2D pAb. RESULTS: FCM analysis proved that both purity and
      activity of obtained NK cells were high.The anti-NKG2D pAb could inhibit
      significantly cytotoxicities of NK and LAK cells to K562 and HepG2 cells, for NK
      cells,having decreased 82.9% and 75.6%, for LAK cells,having decreased 52.8% and
      50.2%, respectively.The anti-NKG2D pAb had no effect on cytotoxicities of NK and
      LAK cells to CNE cells. CONCLUSION: The anti-NKG2D pAb can inhibit cytotoxocities
      on tumor cells by NK and LAK cells through NKG2D molecule on two effector cells.

PMID- 15155088
TI  - [Effects of Th1 cytokine gene on anti-CFP10 antibody production in BALB/c mice
      induced by Mycobacterium tuberculosis DNA vaccine].
AB  - AIM: To investigate the effects of plasmid containing mouse IL-12 and human IL-18
      genes on the humoral immune response of mice immunized by CFP10 gene of
      Mycobacterium tuberculosis (MTB) H(37)R(v) strain. METHODS: Human IL-18 cDNA was
      amplified from RNA of PBMCs by RT-PCR and cloned into the pGEM-Teasy vector.
      After sequencing it was subcloned into the the sites of BamH I and EcoR I
      digestion of pcDNA3.1. BALB/c mice were injected intramuscularly by eukaryotic
      expression plasmid pcmIL12 and pcIL18, together with MTB CFP10 DNA vaccine,
      respectively. The same immunization repeated three times at intervals of two
      weeks. Mouse sera were collected at two weeks after the each injection. The titer
      of anti-CFP10 antibody was detected by ELISA. RESULTS: IL-18 cDNA was amplified
      successfully from RNA of human PBMCs by RT-PCR and the result of sequencing was
      correct. The IL-18 gene was correctly inserted into the vector pcDNA3.1 by being
      confirmed with BamH I and EcoR I digestion analysis, positive plasmid was called
      pcIL18. After being immunized with pcCFP10 three times, the end point titer of
      anti-CFP10 was 1:4 000, while the titer obtained by being immunized with pcIL18 +
      pcCFP10 was 1:8 000, but yet, after being immunized with pcmIL12+pcCFP10, the end
      point titer of anti-CFP10 antibody was only 1:200. CONCLUSION: Combination of IL
      18 gene with MTB CFP10 DNA vaccine can enhance the humoral immune responses to
      pcCFP10, whereas the immunization with IL-12 gene plus pcCFP10 made humoral
      immune response markedly descent. As for whether IL-18 gene plus MTB CFP10 DNA
      vaccine can induce markedly the cellular mediated immune response to CFP10 or not
      remains to be further investigated.

PMID- 15155089
TI  - [Preparation and identification of polyclonal antibody to B cell epitope domain
      of TRP-1].
AB  - AIM: To prepare the polyclonal antibody to B cell epitope domain of TRP-1 and
      apply it to study the immunotherapy of vitiligo and melanoma. METHODS: The fusion
      protein PRSETA/TRP-1 was expressed in E.coli, the polyclonal antibody was
      prepared by immunizing a rabbit with the protein. The qulity of the antibody was
      identified by ELISA and Western-blot. RESULTS: (1)The pRSEA/TRP-1 fusion protein
      was correctly expressed;(2)the polyclonal antibodies to the B cell eoitope domain
      of TRP-1 were obtained; (3)the rabbit antiserum containing of polyclonal antibody
      showed high titer and possessed good binding activity to 6His-TRP1 expressed by
      Pichia pastoris. CONCLUSION: The polyclonal antibody could be applied to the
      research on B cell epitope domain of TRP-1.

PMID- 15155090
TI  - [Construction of phage anti-idiotypic antibody library using sensitized in-vitro
      B-lymphocytes of nasopharyngeal cancer patients].
AB  - AIM: To construct phage human anti-idiotypic antibody library. METHODS:
      Peripheral blood mononuclear cells(PBMCs) of patients with nasopharyngeal
      cancer(NPC) were sensitized in-vitro and transformed by Epstein-Barr virus(EBV).
      V(H) and V(L) genes were re-amplified by PCR and combined to single-chain
      fragment of variable region(ScFv) genes. ScFv genes were cloned into vector fUSE5
      and transformed into MC1061 by electroporation to construct the ScFv-displaying
      phage library. RESULTS: Detection of Sandwich ELISA showed that of 10 NPC
      patients,8 patients' B cells transformed by EBV could produce anti-idiotypic
      antibodies to NPC. 5 types of V(H) genes and 7 types of V(L) genes were obtained
      by PCR re-amplification and then connected with (Gly(4)Ser)(3) linker to form 14
      types of ScFv genes. ScFv genes digested with Sfi I were cloned into vector fUSE5
      and transformed into MC1061 via electroporation. Phage anti-idiotypic antibody
      library with sink size being 1.1x10(7) was obtained through tetracycline
      resistant secreening. The percentage of full-length ScFv gene inserted into phage
      DNA was 70%. CONCLUSION: A strategy for preparing human single chain anti
      idiotypic antibody by means of phage antibody library technique in combination
      with EBV transformation technique is feasible.

PMID- 15155091
TI  - [Studies on the antithrombotic effects of anti-platelet mAb SZ-21 F(ab')(2)
      fragment].
AB  - AIM: To research the biological effect of the F(ab')(2) of anti-platelet GPIIIa
      mAb SZ-21. METHODS: The F(ab')(2) fragment was obtained with papain digestion for
      20 hours at 4 degrees Celsius, under acid condition(pH 5.5). The products were
      purified through DEAE-52 ion exchange column and the first eluted peak components
      were verified as F(ab')(2) by SDS-PAGE. The immunoactivity and its antithrombotic
      effects of fragment were detected by ELISA and platelet aggregation inhibition
      test, respectively. RESULTS: The recovery rate of the fragment was 60.32%, its
      immunoactivity was 0.8 x10(-9) mol/L by ELISA. The 50% effective dose (ED(50)) in
      the platelet aggregate inhibition test was 3.395 mg/L. CONCLUSION: The F(ab')(2)
      fragment was superior to intact IgG in binding to platelets and inhibiting
      platelet aggregation. Thus the F(ab')(2) fragment of mAb SZ-21 opens up broad
      prospects for its application to the clinical antithrombotic therapy.

PMID- 15155092
TI  - [Analysis on patial amino acid sequence of a novel glycoprotein binding to
      antiherpes simplex virus monoclonal antibody CHA9].
AB  - AIM: To acquire the characteristic amino acid sequence of a novel glycoprotein of
      herpes simplex virus (HSV), so as to localize gene encoding the novel
      glycoprotein accurately. METHODS: A 12-mer phage peptide library was screened for
      3 rounds by using biotinylated mAb CHA9 against new glycoprotein g30k of HSV-2.
      Positive phage clones were detected by ELISA. 10 positive clones were selected
      randomly for sequencing. Sequence alignment and hydrophobic cluster analysis were
      carried out. RESULTS: Most of the sequences of 10 positive phage clones were
      highly homologous with a core-PH/KHXHXGS-. Phages containing this motif could
      react specifically with the mAb CHA9 and not cross-react with other IgG.
      Hydrophobic cluster analysis showed that the peptide was likely to form an
      epitope. CONCLUSION: We obtained a characteristic short peptide which shows some
      characters of g30K amino acid sequence. It provides valuable clue for prediction
      of the open reading frame of g30K gene and will be useful to explore biological
      characteristics of the new glycoprotein.

PMID- 15155093
TI  - [A novel cis-acting enhancer element between CKLF and CKLFSF1 genes].
AB  - AIM: To explore the roles of the CKLF gene and CKLFSF1 gene sequence (CCS) in
      transcriptional regulation. METHODS: The target gene fragment was amplified by
      PCR and then inserted into pGL3-basic and pGL3-SV40 containing luciferase
      reporter vector gene to construct pGL3-basic-CCS and pGL3-SV40-CCS. Using
      liposome-mediated method, four recombinant plasmids were respectively transfected
      into Hela cells. Transient expression was analyzed. RESULTS: The luciferase assay
      indicated that the no luciferase activity was detected in Hela cells transtected
      with pGL3-basic and pGL3-basic-CCS. However, the luciferase activity was doubled
      when pGL3-SV40-CCS was transfected into Hela cells. CONCLUTION: The CCS has no
      promoter activity, whereas some important cis-acting enhancer elements which
      modulate its downstream gene expression may exist within this sequence.

PMID- 15155094
TI  - [Development of a rapid quantitative double mAb sandwich ELISA for detecting
      galactomannan antigen of aspergillus fumigatus].
AB  - AIM: To develop a double mAb sandwich ELISA for rapidly and quantitatively
      detecting galactomannan (GM) antigen of aspergillus fumigatus. METHODS: Four
      monoclonal antibodies (mAb) against GM of aspergillus fumigatus were used as
      coating or enzyme conjugated antibodies respectively. Capture and sandwich mAbs
      were selected by sandwich ELISA paired one by one. RESULTS: Optimal capture and
      sandwich mAbs were selected and a highly sensitive double sandwich ELISA
      established. The sensitivity of detecting GM reached 0.1 microg/L, the detectable
      range was 0.1-10 microg/L. Coefficient of variation (C.V) obtained from detecting
      the same sample for 6 times by ELISA was (7.2+/-3.8)%. CONCLUSION: A sensitive,
      repeatable and rapid double mAb sandwich ELISA was established for quantitation
      of aspergillus fumigatus GM, which might apply to early diagnosis and treatment
      of patients with aspergillosis.

PMID- 15155095
TI  - [The expression of fusion protein GST-GP302 in E.coli and its preparation of
      rabbit anti-serum].
AB  - AIM: To express fusion protein of GST and vWf binding domain(GP302) of platelet
      GPIbalpha in E.coli and its preparation of rabbit anti-serum. METHODS: GP302 gene
      was inserted into pGEX-4T-1. The recombinant vector was identificated by
      restriction endonuclease digestion analysis. Fusion protein GST-GP302 was
      expressed in E.coli via IPTG induction. The rabbit antibody against GST-GP302 was
      prepared by using renatured GST-GP302 as immuneogen and the specificity of
      polyclonal antibody was identified by Western blot. RESULTS: The restriction
      endonuclease digestion analysis of recombinant plasmid demonstrated that the
      GP302 gene had been exactly inserted into pGEX-4T-1. SDS-PAGE analysis showed
      that the ralative molecular mass(M(r)) of the fusion protein was about 59 000.
      ELISA analysis proved that the titer of rabbit serum against GST-GP302 was 10(
      5). The polyclonal antibody specifically bound to purified platelet GPIbalpha.
      CONCLUSION: The preparation of polyclonal antibody against GP302 peptide provides
      an usefal reagent for the detection of platelet GPIbalpha.

PMID- 15155096
TI  - [Shistosoma japonicum: dynamics of cytokine production induced by immunization of
      mice with recombinant GST-Sj32 protein before and after challenge infection].
AB  - AIM: To explore the mechanism of protective immunity of rGST-Sj32. METHODS:
      BALB/c mice were immunized subcutaneously with rGST-Sj32 emulsified with Freund's
      complete adjuvant. Five mice from each group were killed prior to immunization,
      prior to challenge and 10 days, 30 days and 45 days post-challenge, respectively.
      Spleen cells from these mice were cultured and levels of cytokine secreted by
      splenocytes were detected by ELISA. RESULTS: Compared with the control group, the
      quantity of IL-4, IL-5 and IFN-gamma released from rGST-Sj32-primed splenocytes
      were increased to varying degrees, being (10.21+/-3.65) ng/L, (19.89+/-9.57) ng/L
      and (5.09+/-2.51) microg/L, respectively. The level of IFN-gamma post challenge
      did not increase in control group and immunization group. The levels of IL- 4 and
      IL-5 in the control group were elevated gradually following challenge, and were
      much higher than those in immunization group. CONCLUSION: The immunization with
      rGST-Sj32 elicited mainly a Th1 type immune response in BALB/c mice, whereas the
      immune response induced by challenge was a Th2 type.

PMID- 15155097
TI  - [Eukaryotic expression and application of human CD226 Ig fusion protein
      containing 3C protease-restricted site].
AB  - AIM: To construct, express and characterize the eukaryotic expression vector of
      encoding human CD226 (PTA1) extracellular region Ig fusion protein gene
      containing 3C protease-restricted site. METHODS: The gene fragment encoding
      extracellular region of human CD226 was cloned into the eukaryotic expression
      vector p-3C-Ig containing 3C protease-restricted site and human Ig Fc fragment
      gene. After sequencing, the vector was transfected into COS7 cells, and the
      expressed molecule was purified by affinity chromatography. Finally, the product
      was characterized by immunofluorescent staining and 3C protease digestion.
      RESULTS: After expression and purification, the Ig fusion protein could bind
      effectively to the CD226 ligand expressed on ECV304 cells. The Fc fragment could
      also be cut off by 3C protease, so that the CD226 extracellular fragment was
      obtained. CONCLUSION: The extracellular region of human CD226 Ig fusion protein
      with 3C protease-restricted site is expressed successfully in COS-7 cells, which
      lays the foundation for the structural and functional study of this molecule.

PMID- 15155098
TI  - [Role of P38 mitogen-activated protein kinase in expression of P-selectin on
      human umbilical vein endothelial cells].
AB  - AIM: To investigate the role of P38 mitogen-activated protein kinase (P38MAPK) in
      expression of P-selectin on human umbilical vein endothelial cells and diabetic
      atherosclerosis. METHODS: Human umbilical vein endothelial cell line ECV304 were
      stimulated with high glucose, advanced glycosylation end products (AGE), high
      insulin and H(2)O(2) respectively, and then expression of phosphorylated-P38MAPK
      and P-selectin was detected after being pre-treated with SB203580 (P38MAPK
      specific inhibitor). RESULTS: High glucose, AGE, high insulin and H(2)O(2) could
      activate P38MAPK by oneself, and increased notably expression of phosphorylated
      P38MAPK and P-selectin on cell line ECV304; Expression of P-selectin was
      inhibited significantly by SB203580. CONCLUSION: P38MAPK can regulate the
      expression of P-selectin, P38MAPK is an upstream signaling molecule and also may
      be one of initial signals on atherosclerosis occurrence.

PMID- 15155099
TI  - [Construction and identification of recombinant retrovirus vector containg hTrx
      gene].
AB  - AIM: To construct a recombinant retrovirus vector carrying hTrx gene. METHODS:
      hTrx gene was cloned directionally into a retroviral vector pLXSN by DNA
      recombinant technique and the recombinant vector was identified EcoRI and BamHI
      digestion analysis. The recombinant was transfected into packaging cells PA317
      via CaPO(4)-based transfection method, and viral titer in culture supernatant of
      transfected cells was detected. RESULTS: The recombinant pLTrxSN had been
      constracted. EcoRI and BamHI digestion analysis displayed two positive bands of
      0.3 kb and 5.9 kb respectively. The viral titer in supernatant of transfected
      cells was 5.5x10(9) cfu/L. CONCLUSION: pLhTrxSN has been constructed
      successfully, which will be useful for Trx gene therapy and experiment study.

PMID- 15155100
TI  - [Retroviral-mediated transfection of hepatitis B virus core gene into bone marrow
      derived dendritic cells].
AB  - AIM: To evaluate the transfection efficiency of recombinant retrovirus vector
      bearing hepatitis B virus(HBV) core gene to bone marrow-derived dendritic
      cells(DCs) and the capability of these DCs to induce cytotoxic T lymphocyte(CTL)
      response. METHODS: C57BL/6 mice bone marrow cells were stimulated with
      recombinant mouse granulocyte-macrophage colony-stimulating factor(rmGM-CSF) and
      interleukin-4(rmIL-4) for 6 days. Expanding DC progenitors were transfected by
      retrovirus vector containing HBV core gene. Integration and transcription of HBV
      core gene were determined by PCR and RT-PCR, respectively. Expression of HBcAg
      was analyzed by fluorescence activated cell sorter (FACS) and Western blot.
      Cytokines were quantified by enzyme immunoassay. The expressions of CD80 and MHC
      class II molecules on DCs were measured by FACS. Generation of CTLs in mixed
      leukocyte reaction were determined by LDH release assays. RESULTS: Transfected
      bone marrow cells were capable of differentiating into DCs in-vitro at the
      presence of rmGM-CSF and rmIL-4. The result of PCR and RT-PCR showed that the HBV
      core gene was integrated into the genome of infected DCs. Western blot analysis
      showed that HBV core gene was expressed in DCs. Transfection rate was 28%
      determined by FACS. Retroviral transfection had no influence on expressions of
      CD80 and MHC class II molecules, as well as IL-12 production. HBcAg-specific CTLs
      could be generated by using transfected DCs as antigen presenting cell (APC).
      CONCLUSION: Retroviral transfected myeloid DC progenitors could efficiently
      express HBcAg, without significant change on development and function of DCs,
      which lays a solid foundation for immunotherapy of chronic hepatitis B.

PMID- 15155101
TI  - [Detection of serum heat shock protein 70 level in patients with hepatitis C
      infection and its role in cytotoxicity of CTLs induced by HSP70-HCV peptide
      complex].
AB  - AIM: To detect serum HSP70 in patients with hepatitis C and evaluate its role in
      cytotoxicity of specific CTLs induced by HSP70-HCV peptide complex. METHODS: The
      serum HSP70 level in patients infected with HCV and normal individuals were
      detected by ELISA. The relationship between anti-HCV antibody and HSP70 was
      evaluated. Peripheral blood mononuclear cells (PBMCs) were activated by HSP70-HCV
      peptide complex and then 4 hour (51)Cr release assay were used to detect the
      killer activity of CTLs. RESULTS: Detection rates of HSP70 were 82.1%(22/28) and
      18.8% (9/48) in patients with anti-HCV antibody and in normal individuals,
      respectively. There was significant correlation between the detection rate of
      HSP70 and HCV infection (chi(2)=28.77, P<0.01). The level of serum HSP70 in
      patients infected with HCV was markedly more higher than that in normal
      individuals. CTLs from one patient induced by HSP70-HCV C region peptide
      (DLMGYIPAV) complex could lyse autologous B lymphoblastoid cell lines (BLcLs)
      with killer rate of 37.8%, whereas CTLs induced by peptide alone could not lyse
      autologous BLcLs cells. CONCLUSION: HCV infection can induce over expression of
      HSP70. HSP70 may have the action of enhancing presentation of HCV epitope peptide
      and promoting clearance cells infected with HCV.

PMID- 15155102
TI  - [Screening of bioactive peptide that mimic the epitope of gastric cancer
      associated antigen].
AB  - AIM: To screen bioactive peptides that mimic the epitope of gastric cancer
      associated antigen. METHODS: Anti-gastric cancer monoclonal antibody (mAb) MG7
      was purified by ion chromatography, and then coated on ELISA plate. By using the
      mAb as selective molecular, a 12-meres phage displaying peptide library was
      biopanned, and the positive clones were selected. RESULTS: 12 positive phage
      clones were selected. CONCLUSION: A candidate mimic epitope of gastric cancer
      associated antigen was identified, which provided the foundation for developing
      tumor peptide vaccine.

PMID- 15155103
TI  - Essential thrombocythaemia in children: is a treatment needed?
AB  - The myeloproliferative disorder, essential thrombocythaemia (ET), is extremely
      rare in children. In adults, thrombosis is the most common complication whereas a
      low number of children develop thrombosis and/or haemorrhages. Diagnosis of ET is
      often difficult, but identifying ET from other causes of thrombocytosis is
      essential, otherwise therapy may be ineffective as the wrong disease will be
      treated. Only anecdotal experiences have been published with regard to the
      treatment of paediatric ET. A watch-and-wait strategy seems appropriate in
      asymptomatic cases and low-dose aspirin should be used to reduce microvascular
      disturbances. Anagrelide or IFNs may be considered as first-line, and hydroxyurea
      as second-line therapy. Anagrelide may become the treatment of choice for ET in
      children if a lack of leukaemogenic potential is confirmed.

PMID- 15155104
TI  - Alternative use of botulinum toxin in urology.
AB  - Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to
      detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor
      deficiency). The toxin acts by producing paralysis of muscle tissue and has been
      shown to be safe and effective in the treatment of conditions caused by increased
      muscle tonicity and spasticity. Here the literature is reviewed chronologically,
      the established and emerging indications for the urological use of botulinum
      toxin evaluated and future applications are also considered.

PMID- 15155105
TI  - Hormone replacement therapy in hypopituitarism.
AB  - Hypopituitarism is a disease complex characterised by varying pituitary hormonal
      deficiencies. The causes and manifestations of hypopituitarism are diverse, the
      most common being the presence of or treatment of a pituitary adenoma. Pressure
      effects from the tumour itself on normal pituitary tissue, together with the
      effects of surgical resection, results in variable degrees of hypopituitarism.
      The latter precipitates end-organ failure leading to a variety of symptoms and
      signs, which are often nonspecific and vague. The broad aims of managing patients
      with hypopituitarism are to provide amelioration of the symptomatology associated
      with the condition, to avoid potentially acute life-threatening complications and
      to protect against long-term sequelae that may include osteoporosis and
      cardiovascular disease. This is achieved through lifelong therapeutic replacement
      of target hormonal deficiencies, such as corticosteroids or sex hormones, or
      replacement of the pituitary hormones themselves (i.e., growth hormone and
      vasopressin). Although the general principle of replacing missing hormones seems
      straightforward, in reality, existing hormonal therapeutic regimes often result
      in unphysiological replacement. Furthermore, there may be problems associated
      with their administration and routine monitoring. There is now little doubt that
      the hypopituitary state is associated with increased cardiovascular mortality.
      However, the precise underlying mechanisms responsible have not been fully
      elucidated, but probably include untreated growth hormone deficiency and/or
      unphysiological replacement of other target hormones. An effective strategy of
      tailoring hormonal replacement regimes to individual needs remains a challenge
      but is imperative if the increased morbidity and mortality associated with
      hypopituitarism is to be addressed.

PMID- 15155106
TI  - Recombinant human follicle-stimulating hormone: a controversial issue--without
      controversy.
AB  - Recent developments in recombinant DNA technology have resulted in a rapidly
      expanding range of new diagnostic and therapeutic opportunities. This technology
      paved the way for identification, isolation, cloning and production of specific
      proteins. Recently, recombinant human gonadotropins became available for clinical
      use. Pharmacokinetics, receptor availability, pharmacodynamics and safety were
      extensively studied and the drugs were found to be identical, if not superior, to
      urinary gonadotropins that have been used in reproductive medicine for the last
      40 years. It is currently apparent that the use of recombinant human
      gonadotropins is expected to provide improved batch-to-batch consistency, steady
      supply and most importantly, a purified compound with highly specific activity,
      which accounts for > 99% of the protein content of the preparation, making it
      possible to administer subcutaneously. The purpose of this report is to describe
      and evaluate recent developments in the use of recombinant human follicle
      stimulating hormone.

PMID- 15155107
TI  - Pharmacotherapy for sexual dysfunction in women.
AB  - In the setting of multiple studies claiming a high prevalence of sexual problems
      amongst women, new conceptualisation of the sexual response in women and
      definitions of sexual dysfunction, which reflect the need for biopsychosocial
      management, are being developed. The biological underpinnings of the sexual
      response in women may be influenced by environmental factors, as well as by
      medications, disease processes and normative changes in endogenous hormones.
      Psychological factors can alter both the physiological processes and the
      experience of sexual response. The new models clarify the importance of sexual
      motivations other than desire, sexual arousability and subtypes of arousal
      disorder. The role of pharmacotherapy to potentially augment desire,
      arousability, genital congestion and to lessen the pain of chronic dyspareunia
      must be envisaged within the holistic biopsychosocial model.

PMID- 15155108
TI  - Treating haemophilia A with recombinant blood factors: a comparison.
AB  - The mainstay in the treatment of haemophilia A is replacement therapy with
      repeated infusions of plasma-derived Factor VIII (FVIII) concentrates or
      recombinant FVIII products. While modern plasma-derived FVIII concentrates have
      an excellent safety profile, there is an inexorable shift towards the use of
      recombinant products, especially in affluent countries. Recombinant FVIII
      products have demonstrated excellent haemostatic efficacy and higher safety with
      regard to the transmission of blood-borne pathogens. The experience in
      haemophilia A treatment with five currently available recombinant FVIII products,
      including the first third-generation product, Advate, which is completely free
      from human or animal proteins, is summarised. Some unresolved problems concerning
      the efficacy and assaying of recombinant factors and future perspectives of both
      recombinant and plasma-derived FVIII products in global haemophilia care, are
      also discussed.

PMID- 15155109
TI  - Are there any benefits of Betoptic S (betaxolol HCl ophthalmic suspension) over
      other beta-blockers in the treatment of glaucoma?
AB  - The cardioselective beta-blocker, betaxolol, is an effective ocular
      antihypertensive agent. Its mode of action in lowering intraocular pressure is
      similar to that of the nonselective blockers, by suppressing the flow of aqueous
      humor. The most frequent adverse reaction to betaxolol is stinging upon
      administration, which is minimised by an ocular suspension with a similarly
      effective twofold reduced concentration (Betoptic S, 0.25%). The extent of beta 1
      adrenoceptor occupancy of topically applied betaxolol in the systemic circulation
      is less than that of the nonselective blockers and beta 2-receptor occupancy is
      negligible, providing a better safety profile in patients with cardiopulmonary
      disease. Experimental studies have revealed that the drug reaches the retina
      after topical administration and displays a voltage-dependent L-type calcium
      channel blocking activity, which probably allows betaxolol to improve retinal
      perfusion and to serve as a neuroprotective agent recommendable in various forms
      of glaucoma.

PMID- 15155110
TI  - The management of dermatomyositis: current treatment options.
AB  - Dermatomyositis is traditionally classified as one of the idiopathic inflammatory
      myopathies. The traditional approach to the management of patients with
      dermatomyositis focuses predominantly on end points related to the systemic
      manifestations of this disorder, especially proximal muscle weakness resulting
      from myositis. However, the primary and secondary skin changes that are
      characteristic of dermatomyositis can, in themselves, produce significant
      morbidity and disability. This article presents a dermatological perspective on
      the management of dermatomyositis. As dermatological management approaches can
      vary between countries, an effort has been made to present a consensus
      dermatological view concerning this subject. A US dermatologist is most likely to
      see patients having dermatomyositis skin lesions in the following four clinical
      settings: soon after the onset of dermatomyositis skin disease activity before
      the appearance of clinically-evident muscle disease (i.e., 'pre-myopathic'
      dermatomyositis); during the course of clinically-amyopathic dermatomyositis;
      during co-management of classical dermatomyositis with other physicians; and for
      recrudescent skin disease activity in classical dermatomyositis patients after
      their symptomatic muscle inflammation has been fully suppressed by systematic
      immunosuppressive/immunomodulatory treatment (i.e., 'postmyopathic'
      dermatomyositis). Both topical and systemic therapies for dermatomyositis skin
      lesions encountered in these various settings will be discussed. In addition to
      specific approaches to the treatment of dermatomyositis skin lesions, broader
      management issues that dermatologists must be aware of when caring for
      dermatomyositis patients are included in this discussion (e.g., patient
      education, risk of associated systemic disease, such as myositis and interstitial
      lung disease, risk for occult malignancy, and prognosis counselling).

PMID- 15155111
TI  - Pharmacotherapy for bipolar depression: an economic assessment.
AB  - Bipolar disorder (BPD) is a common, severe and recurrent mood disorder associated
      with high rates of comorbidities, suicide, dysfunction and a high socioeconomic
      burden. Although the management of BPD has traditionally focused on the acute
      treatment of mania, the chronic nature of BPD necessitates long-term maintenance
      treatment. Bipolar depression is the predominant abnormal affective pole and
      causes greater disability and economic burden than mania. Maintenance
      pharmacotherapy can reduce rates of future episodes, and subsequently, the
      associated risks, functional disability and economic burden of bipolar illness.

PMID- 15155112
TI  - Psychopharmacology of conduct disorder: current progress and future directions.
AB  - Behavioural manifestations of conduct disorder (CD) among children and
      adolescents are one of the most common referrals to community psychiatrists.
      Patients with CD are difficult to treat. The patterns of maladaptive behaviours
      they exhibit are diverse and can vary as a function of age and gender. Although
      different pharmacological interventions have been reported as potentially
      promising options in the treatment of CD, no medication has yet received a formal
      approval from the licensure authorities, either in the US or Europe. This article
      reviews efficacy results and associated adverse effects from selected clinical
      trials that have the strongest outcome evidence for the treatment of CD in
      children and adolescents. Critical issues in the effectiveness of the evidence
      based pharmacotherapy for CD are raised and future directions of the
      psychopharmacology of CD are examined.

PMID- 15155113
TI  - Gemifloxacin: a new fluoroquinolone.
AB  - Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity
      against Gram-positive, -negative and atypical human pathogens--pathogens
      considered to be important causes of community-acquired respiratory tract
      infections. Gemifloxacin demonstrates impressive minimal inhibitory
      concentrations (MIC 90 ) values against clinical isolates of Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae
      and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06,
      0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is
      also active in vitro against a broad range of Gram-negative bacilli with MIC 90
      values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml (
      Escherichia coli and Providencia stuartii, respectively), with the majority of
      the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro
      activity of gemifloxacin against anaerobic organisms is variable. The MIC values
      for gemifloxacin are not affected by beta-lactamase production nor by penicillin
      or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to
      be clinically efficacious against multi-drug resistant S. pneumoniae. The
      pharmacokinetics of gemifloxacin are such that the drug can be administered
      orally once-daily to yield or achieve sustainable drug concentrations exceeding
      the MIC values of clinically important organisms. Gemifloxacin has been shown to
      target both DNA gyrase (preferred target) and topoisomerase IV (secondary target)
      - enzymes critical for DNA replication and organism survival - against clinical
      isolates of S. pneumoniae. This dual targeting activity is thought to be
      important for reducing the likelihood for selecting for quinolone resistance.
      Gemifloxacin has been investigated and approved for therapy in patients with
      community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis.
      In one study, more patients receiving gemifloxacin compared to clarithromycin
      remained free of exacerbations for longer periods of time (p < 0.016) and
      gemifloxacin had a shorter time to eradication of H. influenzae than did
      clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have
      an adverse profile that was comparable with other compounds. The most frequent
      side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a
      welcomed addition to currently available agents for the treatment of community
      acquired lower respiratory tract infections. Other potential indications appear
      to be within the spectrum of this compound.

PMID- 15155114
TI  - A review of teriparatide and its clinical efficacy in the treatment of
      osteoporosis.
AB  - Until recently, antiresorptive medications such as bisphosphonates and raloxifene
      represented the main pharmacological treatment options for patients with
      osteoporosis. With the introduction of teriparatide (rhPTH (1-34) ), a
      recombinant formulation of parathyroid hormone (PTH) consisting of the first 34
      amino acids of the N -terminal region, bone-forming therapy has now become
      possible. Preclinical, as well as human studies, have shown increases in
      trabecular as well as cortical bone mass with subsequent improvements in bone
      microstructure and cortical thickness. The subcutaneous daily dose of
      teriparatide 20 microg has been shown to decrease the occurrence of new vertebral
      fractures in caucasian women (70 years of age) by 65%, in a large randomised,
      double-blind placebo-controlled trial. Moderate-to-severe fractures or multiple
      vertebral fractures could be reduced by 90 and 77%, respectively. There was also
      a significant beneficial effect on new nonvertebral fractures (-35%) by the end
      of the 21-month treatment period. The reduction in nonvertebral fractures became
      evident after approximately 8 - 12 months of treatment. Smaller studies in men
      with low bone mass showed similar effects on bone mineral density and changes in
      bone turnover markers when compared to the results obtained in postmenopausal
      women. Recent data suggest that teriparatide is best given as monotherapy and not
      in combination with a bisphosphonate. Previous bisphosphonate treatment is also
      likely to diminish the bone anabolic potential of teriparatide. In order to
      preserve bone mass gained during the recommended 18- to 24-month treatment
      period, antiresorptive medication should be prescribed following teriparatide
      treatment. Studies so far have not shown serious PTH-related side effects.
      Hypercalcaemia is usually mild and transient and the osteosarcoma risk reported
      in rat toxicology studies is very unlikely to be predictive of a similar risk in
      humans. As teriparatide is expensive, its use at the moment should be limited to
      patients with more severe forms of osteoporosis, usually with the presence or
      history of one or more fractures because of those patients' high risk for
      subsequent fractures.

PMID- 15155115
TI  - Flunisolide HFA for the treatment of asthma: an old friend reformulated.
AB  - The environmental mandate to eliminate the production of ozone-depleting products
      including chlorofluorocarbon (CFC) propellants has encouraged much needed
      research into improving modes of delivery of inhaled corticosteroids and
      enhancing drug deposition. Consequently, flunisolide CFC, an inhaled
      corticosteroid with a proven track record in the treatment of asthma, has been
      reformulated using a hydrofluoroalkane (HFA) as a propellant and is now awaiting
      FDA approval. Flunisolide HFA is a solution aerosol, unlike flunisolide CFC which
      is a suspension aerosol. As a solution aerosol, flunisolide HFA has a smaller
      mean particle size than flunisolide CFC. In addition, the built-in spacer
      included in the flunisolide HFA inhaler acts to reduce ex-actuator particle size;
      the smaller particle size of flunisolide HFA results in an improved deposition
      profile. Flunisolide HFA has substantially more lung deposition and much less
      oropharyngeal deposition than flunisolide CFC. Limited information is currently
      available on the clinical performance of flunisolide HFA. A single dose-response
      study has been performed in adults and in children comparing multiple doses of
      flunisolide HFA and flunisolide CFC. These studies indicate that flunisolide HFA
      is effective in controlling asthma. No unusual safety concerns have been noted,
      although further studies are needed to determine the long-term systemic effects
      of flunisolide HFA.

PMID- 15155116
TI  - Etanercept: a clinical review of current and emerging indications.
AB  - The recent development of inhibitors of TNF-alpha has provided the opportunity
      for a more targeted and highly effective approach to the treatment of chronic
      inflammatory illnesses such as rheumatoid arthritis. Since the initial approval
      of etanercept as a treatment for rheumatoid arthritis, additional indications,
      including psoriatic arthritis, juvenile rheumatoid arthritis and ankylosing
      spondylitis, have also received FDA approval. More than 220,000 patients have
      been treated with etanercept so far. This review summarises the body of knowledge
      accumulated so far on etanercept (Enbrel) since it entered the market 5 years
      ago.

PMID- 15155117
TI  - Investigating cardiovascular risk reduction--the Rosuvastatin GALAXY Programme.
AB  - The GALAXY Programme is a comprehensive global research initiative that will
      address several important unanswered questions in statin research and investigate
      the impact of rosuvastatin on cardiovascular risk reduction and patient outcomes.
      Studies already completed demonstrate that rosuvastatin provides greater
      reductions in low-density lipoprotein cholesterol (LDL-C) than other statins,
      enabling more patients to achieve LDL-C treatment goals. Additionally,
      rosuvastatin provides beneficial effects on other components of the atherogenic
      lipid profile. Ongoing studies will evaluate whether these effects translate into
      beneficial effects on atherosclerosis and significant reductions in
      cardiovascular events. Important information will also be provided on the role of
      statins in less well studied groups, including patients with heart failure, end
      stage renal disease, and individuals without elevated LDL-C but at heightened
      vascular risk as a result of increased systemic inflammation. Ultimately, the
      GALAXY Programme will provide clinical data that will enable physicians to make
      more effective statin treatment decisions, which will lead to improved patient
      care and cardiovascular outcomes.

PMID- 15155118
TI  - Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and
      in Combination with Ramipril Global End point Trial programme.
AB  - Hypertension is one of the most important modifiable risk factors for
      cardiovascular pathology, such as atherosclerosis and cardiac left ventricular
      hypertrophy, including acute events such as stroke and myocardial infarction
      (MI). In particular, the risk of ischaemic and haemorrhagic stroke is directly
      and continuously related to high blood pressure levels. The renin-angiotensin
      system (RAS) plays an important role in volume homeostasis and blood pressure
      regulation. It also helps to prevent cell and organ damage from ischaemia during
      acute volume loss. However, angiotensin-II (A-II)--the main effector peptide of
      the RAS--also exerts a number of pathological effects, which are mediated by the
      AT 1 receptor. The Ongoing Telmisartan Alone and in Combination with Ramipril
      Global End point Trial (ONTARGET) programme consists of two parallel trials where
      ONTARGET as a large, long-term study compares the efficacy of the angiotensin
      receptor antagonist, telmisartan, the renin-angiotensin-converting enzyme (ACE)
      inhibitor, ramipril and combination therapy with telmisartan plus ramipril for
      reducing cardiovascular and cerebral risk. Telmisartan, due to its long duration
      of action, compares favourably with other angiotensin-receptor antagonists. In
      the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was shown to
      reduce the risk for MI and other cardiovascular events in patients at high risk
      for pathological cardiac events, but without heart failure or a low ejection
      fraction. The cardiovascular outcomes of high-risk patients using the same
      criteria as those of the HOPE study will be assessed in both trials. TRANSCEND
      differs from ONTARGET in that this trial will enrol patients who do not tolerate
      ACE inhibitors. This parallel study will therefore be able to compare telmisartan
      and placebo treatment. Both ONTARGET and TRANSCEND trials feature the same
      primary composite end point: death caused by cardiovascular disease, acute MI,
      stroke and hospitalisation because of congestive heart failure. The secondary end
      points will focus on reductions in the development of Type 2 diabetes mellitus,
      nephropathy, cognitive decrease and dementia as well as atrial fibrillation.

PMID- 15155119
TI  - Combination of finasteride and doxazosin for the treatment of benign prostatic
      hyperplasia.
AB  - Finasteride, which inhibits the enzyme 5 alpha-reductase, reduces prostate size
      and relieves the symptoms of benign prostatic hyperplasia (BPH) in men with
      enlarged prostates. alpha 1 -Adrenoceptor antagonists, such as doxazosin and
      terazosin, are also effective in the treatment of BPH. Previous clinical studies
      in which finasteride had little or no effect alone, have shown little or no
      additive effect with alpha 1 -adrenoceptor antagonists. The Medical Therapy of
      Prostatic Symptoms study showed a considerable benefit with finasteride alone and
      an additive effect when administered with doxazosin. One interpretation of these
      results is that if finasteride is effective alone in BPH, the combination with an
      alpha 1 -adrenoceptor antagonist will give an additive effect.

PMID- 15155120
TI  - Effects of ADP-receptor antagonism beyond traditional inhibition of platelet
      aggregation.
AB  - Atherothrombosis, or thrombus formation, at the site of a disrupted
      atherosclerotic plaque is the common pathophysiology related to myocardial
      infarction, ischaemic stroke and peripheral arterial disease. A growing body of
      evidence demonstrates an important role for vascular inflammation in the
      pathophysiology of atherosclerosis/atherothrombosis and the importance of the
      platelet as a mediator of inflammation. Clopidogrel is an ADP receptor antagonist
      that is superior to acetylsalicylic acid (ASA) for the prevention of ischaemic
      stroke, myocardial infarction and vascular death in patients with symptomatic
      atherosclerosis. The use of clopidogrel as well as ASA provides sustained,
      incremental benefit in patients with coronary manifestations of atherothrombosis.
      Recent evidence indicates that clopidogrel reduces markers of vascular
      inflammation across the cerebrovascular, coronary and peripheral circulations.
      These effects are not observed after treatment with ASA alone. Further studies
      have revealed that clopidogrel may have potential anticoagulant effects and may
      inhibit arterial vasoconstriction. These broader effects may contribute to the
      protective benefits of clopidogrel and should be considered when evaluating
      antiplatelet agents and optimising antiplatelet regimens.

PMID- 15155121
TI  - Current status of drug receptor nomenclature: receptor closure? The role of NC
      IUPHAR.
AB  - Pharmacology is at a crucial point, because we now have access to sequences, by
      homology, for almost all of the receptors in the human genome. The International
      Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification
      (NC-IUPHAR) has set up > 50 subcommittees to define the receptors, and their
      recommendations, when approved, are posted on a website freely available to all
      scientists. A major new effort is to functionally define relevant receptor
      polymorphisms. This initiative is open to all, and works only because of the
      freely given voluntary effort of scientists.

PMID- 15155122
TI  - Novel uses for current and future direct thrombin inhibitors: focus on
      ximelagatran and bivalirudin.
AB  - Ximelagatran and bivalirudin are direct thrombin inhibitors that have been
      studied for the prevention and treatment of thrombosis and have potential
      advantages over the traditional indirect thrombin inhibitors (i.e., warfarin,
      unfractionated heparin and low molecular-weight heparin). They are both
      reversible inhibitors of thrombin and block both circulating and fibrin-bound
      thrombin. Ximelagatran and bivalirudin possess favourable pharmacokinetic and
      pharmacodynamic profiles including wider therapeutic indices, faster onsets of
      action and less interpatient variability compared to indirect thrombin
      inhibitors. Ximelagatran has shown favourable clinical trial results in venous
      thromboembolism prophylaxis and atrial fibrillation. Similarly, bivalirudin has
      shown positive results in patients with acute coronary syndromes, however,
      further investigation is needed. Ximelagatran and bivalirudin have shown
      promising results in the management of thrombosis and the results of future
      studies confirming their use for the aforementioned indications are anticipated.

PMID- 15155123
TI  - Urotensin-II and the cardiovascular system--the importance of developing
      modulators.
AB  - Urotensin-II (U-II) potently contracts some large isolated blood vessels and
      cardiac tissue. However, the maximum effects on human blood vessels and heart are
      relatively small. U-II dilates human resistance arteries. It markedly decreased
      myocardial function and increased vascular resistance in cynomolgus monkeys, but
      the major effects of U-II have not been observed in healthy humans. A major role
      for U-II in human cardiovascular disease has not been clearly established despite
      studies in patients with coronary artery disease, heart failure, essential
      hypertension and diabetes. Peptide and non-peptide agonists and antagonists of
      the U-II receptor are being developed and will be useful in the characterisation
      of the effects of U-II, and may have some therapeutic potential.

PMID- 15155124
TI  - Selective activators of thyroid hormone receptors.
AB  - An excess of thyroid hormone (TH) leads to a mix of deleterious (increased heart
      rate, muscle wasting and osteoporosis) and beneficial effects (reduced serum
      cholesterol and lipoprotein A and weight loss). All of these actions are mediated
      by nuclear thyroid hormone receptors (TRs), however, genetic evidence suggests
      that different TR isoforms do not contribute equally to individual TH effects.
      Thus, TR isoform selective activators could mimic the beneficial aspects of TH
      excess while avoiding the harmful effects. This article reviews new selective TR
      activators, their mechanism of action (they work by targeting the TR-beta
      isoform) and their actions in animal models. It is clear that these compounds
      represent a promising new avenue for the treatment of lipid disorders and
      obesity.

PMID- 15155125
TI  - Novel pharmacological therapies for the treatment of AIDS-related Kaposi's
      sarcoma.
AB  - Kaposi's sarcoma (KS) is the most common cancer associated with AIDS. KS
      aetiology and pathogenesis are still poorly defined and no definitive treatment
      has yet been identified. However, the introduction in 1996 of highly active
      antiretroviral therapy as a standard of care for those infected with HIV-1
      determined a strong protection against the development of opportunistic
      infections, as well as a remission of pre-existing complications, including KS.
      Under highly active antiretroviral therapy, KS in particular has shown the
      highest clinical response rate reported to date among AIDS patients. Furthermore,
      recent insights into the pathogenetic mechanisms involved in KS development have
      provided new hope for a response and improved survival in patients with AIDS
      related KS. This paper presents an overview of the current knowledge concerning
      pharmacological approaches to treating this disease. Newer treatments such as
      PEGylated liposomal anthracyclin, paclitaxel and pathogenesis-based strategies
      are also discussed.

PMID- 15155126
TI  - The therapeutic potential of glycine transporter-1 inhibitors.
AB  - While current antipsychotic medications are often efficacious for the positive
      symptoms of schizophrenia, there remains a critical need for compounds with
      improved tolerability and efficacy for the negative symptoms and cognitive
      dysfunction associated with this disease. There is a growing body of evidence
      suggesting that the potentiation of N -methyl-D-aspartate (NMDA) receptor
      function may be a useful approach for the treatment of schizophrenia. One
      proposed strategy for this potentiation is to increase synaptic levels of the
      neurotransmitter glycine by blocking the glycine transporter-1. Since glycine
      acts as a required co-agonist for the NMDA receptor complex; this approach allows
      an increase in the effectiveness of normal glutamatergic signalling at the NMDA
      receptor complex. Recent preclinical research, focused on the development and
      testing of novel glycine transporter-1 inhibitors, suggests that this approach
      may be feasible. Converging clinical evidence suggesting therapeutic efficacy
      following the potentiation of glycinergic activity further supports this
      approach. Clinical studies with novel glycine re-uptake inhibitors will provide
      critical information regarding the therapeutic utility and tolerability of this
      treatment for schizophrenia and other disorders associated with NMDA receptor
      hypofunction.

PMID- 15155127
TI  - Platelet activation in the hypertensive disorders of pregnancy.
AB  - The hypertensive disorders of pregnancy, including gestational hypertension, pre
      eclampsia and eclampsia, continue to be an important cause of maternal morbidity
      and mortality. Abnormal placentation is considered to be the main instigating
      factor, which then leads to widespread maternal endothelial activation and
      dysfunction. This endothelial perturbation leads to the release of many
      substances into the circulation, many of which result in platelet activation. For
      example, there is an imbalance between the levels of prostacyclin (a vasodilator
      and platelet inhibitor) and thromboxane (a platelet activator and
      vasoconstrictor), which then results in the maintenance of high blood pressure
      and complications. It is also likely that platelets play an important part in the
      pathogenesis of hypertension in pregnancy. The use of antiplatelet drugs has been
      shown to be effective in reducing the incidence of gestational hypertension in
      women at high risk and in preventing the complications associated with it. In
      addition, some antihypertensive agents are effective in reversing platelet
      activation in essential hypertension and, therefore, their use in pregnancy
      induced hypertension may be beneficial in more ways than simply blood pressure
      reduction.

PMID- 15155128
TI  - Gallium nitrate for the treatment of non-Hodgkin's lymphoma.
AB  - Mortality from non-Hodgkin's lymphoma (NHL) is high, thus defining the need for
      additional therapeutic agents for this disease. Gallium nitrate is a metal
      compound that is presently approved for the treatment of hypercalcaemia
      associated with malignancy. In clinical trials first conducted over two decades
      ago, this drug was found to have antineoplastic activity in NHL. However, its
      development as an antineoplastic agent for the treatment of NHL was never
      rigorously pursued. Gallium has unique mechanisms of action that include its
      binding to transferrin in the circulation and targeting transferrin receptors
      present on lymphoma cells. As it shares chemical properties with iron, gallium
      can disrupt critical steps in iron homeostasis that are essential for tumour cell
      viability and growth and can inhibit the iron-dependent activity of
      ribonucleotide reductase. The drug may also target other cellular processes
      unrelated to iron. Phase I/II studies have shown that gallium nitrate displays
      the most efficacy and lowest toxicity in NHL when administered as a continuous
      intravenous infusion, producing response rates of 43% in patients with relapsed
      or refractory NHL. It does not suppress the white blood cells or platelets and
      does not share cross-resistance with other chemotherapeutic drugs. These
      characteristics make it particularly attractive for the treatment of
      myelosuppressed patients and for incorporation into combination therapy. Multi
      institutional Phase II clinical trials are in progress to evaluate gallium
      nitrate as a single agent or in combination. These studies will help define its
      role in the current treatment of NHL.

PMID- 15155129
TI  - Efaproxiral: a novel radiation sensitiser.
AB  - Efaproxiral (RSR13) is a synthetic allosteric modifier of haemoglobin that
      reduces its oxygen binding affinity. By facilitating the release of oxygen from
      haemoglobin, efaproxiral causes an increase in whole blood P 50 (partial pressure
      of oxygen which results in 50% haemoglobin saturation) and an increase in the PO2
      (partial pressure of oxygen) in the tissue. The therapeutic strategy of enhancing
      oxygen unloading from haemoglobin to tissue emulates and amplifies physiological
      tissue oxygenation and can enhance the oxygenation of hypoxic tumours. Since
      hypoxia is known to decrease the effectiveness of radiation therapy, the use of
      efaproxiral as a radiation sensitiser may be advantageous. Unlike previous
      radiation sensitisers, efaproxiral does not need to enter the cancer cells to
      increase radiosensitivity. Phase I-III trial data have defined the safety profile
      and dosing of the drug, with the potential benefit for extended survival.

PMID- 15155130
TI  - Efalizumab for psoriasis?
AB  - Psoriasis is a chronic skin disorder characterised by inflammation producing red,
      thickened areas with a flaky white build-up. Efalizumab is a humanised monoclonal
      IgG1 antibody that inhibits the binding of T lymphocytes to endothelial cells and
      their subsequent migration. In patients suffering from plaque psoriasis, there
      was improvement in 51-52% of the efalizumab-treated patients at week 12, compared
      with 17% of the placebo patients. Efalizumab caused a > 75% improvement in 22-28%
      of psoriasis patients compared with 5% of placebo patients. Efalizumab also
      improved quality-of-life outcomes. Early studies are also showing benefits with
      other compounds (alefacept, infliximab and etanercept) in psoriasis. Direct
      comparative clinical trials will be needed to ascertain which of these agents
      provides the maximal improvement with the minimal incidence of side effects.

PMID- 15155131
TI  - 2nd International Conference on Immune-Mediated Diseases & 8th International Anti
      Inflammation Meeting.

PMID- 15155132
TI  - HIV entry and fusion inhibitors.
AB  - Human immunodeficiency virus (HIV) is a retrovirus that is the causative agent of
      acquired immunodeficiency syndrome (AIDS). Current HIV therapy is based on
      targeting two critical enzymes in the viral replication machinery: reverse
      transcriptase and a virally encoded protease. Although mortality rates due to HIV
      infection have been dramatically reduced, AIDS remains a major health problem
      throughout the world. The emergence of HIV variants that are resistant to current
      therapies and potential toxicity associated with their chronic use has
      highlighted the need for new approaches to HIV inhibition. Identification of the
      mechanisms underlying viral entry into the host cell has provided a number of
      novel therapeutic targets and the first of these HIV fusion inhibitors
      (enfuvirtide [pentafuside, T-20, Fuzeon; Roche Laboratories and Trimeris]) has
      recently been approved in the US and Europe. This review will focus on recent
      progress in the development of therapeutics that target the HIV entry process.

PMID- 15155133
TI  - Potential therapeutic targets for neurokinin-1 receptor antagonists.
AB  - The peptide substance P and its tachykinin receptor, neurokinin-1 (NK1), have
      been the focus of considerable research for their role in a variety of both
      central and peripheral diseases. Recent preclinical data, as well as relevant
      clinical findings, support the potential therapeutic value of NK1 receptor
      antagonists in centrally mediated disease states, including anxiety and
      depression. In addition, a separate body of literature supports the use of NK1
      receptor antagonists as inhibitors of centrally mediated emetic and cough
      responses. The role of NK1 receptor antagonists as analgesic agents with
      potential to treat migraine headache has also been investigated. NK1 receptors
      are also found in a number of peripheral regions, including the bladder,
      gastrointestinal tract and bone marrow. Preclinical models have been employed to
      address the potential therapeutic uses for NK1 receptor antagonists in diseases
      associated with inflammatory responses, including asthma, irritable bowel
      syndrome and cystitis of the bladder. Finally, other more recent publications
      suggest a role for NK1 receptor antagonists as tumour suppressants and
      haematopoietic agents. These applications for NK1 receptor antagonists are
      discussed in this review.

PMID- 15155134
TI  - The clinical application of monoclonal antibody therapies in renal
      transplantation.
AB  - Monoclonal antibodies have become valuable tools for the precise clinical
      manipulation of the immune system. These highly specific proteins have proven
      their usefulness in both the treatment and prevention of organ transplant
      rejection. Indeed, they are the centrepieces of many evolving regimens designed
      to reduce or eliminate the need for chronic immunosuppression. This manuscript
      will review the monoclonal antibodies that have made their way into the clinic
      either as experimental therapies or approved drugs. It will provide a general
      overview of this class of agents and their mechanisms of action. Standard
      therapies and potential new applications will be described.

PMID- 15155135
TI  - Advances in pharmacotherapy for tobacco dependence.
AB  - The discovery that bupropion is an effective treatment for tobacco dependence has
      triggered a rapid increase in development of potential new non-nicotine
      pharmacotherapies, including bromocriptine, glucose, GTS-21, reboxetine,
      rimonabant, selegeline and varenicline. Successful new products will need to have
      excellent side-effect profiles in addition to proven efficacy. New faster
      delivery nicotine replacement products have the promise of addressing a broader
      list of indications, including treatment of nicotine withdrawal during temporary
      abstinence and long-term nicotine maintenance. Nicotine vaccines will need to
      demonstrate efficacy and also improve certain consumer acceptability
      characteristics (e.g., frequency of injections required) before they can become
      widely used and successful therapies. The best hope of improved treatment comes
      from combining existing and new pharmacotherapies with effective behavioural
      therapy.

PMID- 15155136
TI  - Emerging treatments in acute myeloid leukaemia.
AB  - Acute myeloid leukaemia (AML) is the most common form of leukaemia in young
      adults. Although 75-85% of patients will achieve complete remission after
      induction chemotherapy, the long-term survival is still < 50% at 5 years.
      Chemotherapy has increased in intensity in recent years and is perceived to have
      reached the limit of toxicity. Allogeneic bone marrow transplantation, which is
      undoubtedly the most effective way to prevent relapse, may not add substantial
      survival benefits. Several new pharmacological approaches to the treatment of AML
      are now becoming available, with various molecular targets identified, including
      the farnesylation of RAS family proteins and tyrosine kinases involved in signal
      transduction and epigenetic methylation. More selective delivery of
      chemotherapeutic agents is also feasible using humanised monoclonal antibodies,
      with the intriguing possibility of increasing treatment delivery without
      increasing the toxicity. However, despite the progress in the rational design of
      drugs in disorders such as chronic myeloid leukaemia, AML lacks a single specific
      pathognomic genetic event to act as a drug target. This review discusses the
      drugs presently under investigation in Phase II or Phase III trials in AML.

PMID- 15155137
TI  - Emerging drugs in pancreatic cancer.
AB  - Improving survival in patients with pancreatic cancer remains a formidable
      challenge. For the few patients with localised stages of the disease, intra
      operative radiotherapy, adjuvant chemoradiotherapy and neo-adjuvant therapies
      remain non-validated and the survival benefit conferred by 5-fluorouracil-folinic
      acid adjuvant chemotherapy over radical surgery alone is still a matter of
      debate. Gemcitabine has recently emerged as the standard single agent in advanced
      stages of the disease and pharmacokinetic refinements such as the use of a fixed
      dose infusion rate may further improve still rather modest result figures. At
      present, most efforts deal with the development of more effective doublet or
      triplet therapies, combining gemcitabine with either conventional cytotoxic drugs
      -the most promising being oxaliplatin--or more innovative, targeted therapeutic
      agents. Among these agents, matrix metalloprotease inhibitors and
      farnesyltransferase inhibitors have already undergone Phase III trials, alone or
      in combination with gemcitabine, with rather disappointing results. However,
      preclinical and Phase I and II studies of cyclooxygenase-2 or lipoxygenase
      inhibitors, various immunotherapeutic approaches and several tyrosine kinase
      inhibitors or monoclonal antibodies against growth factors or their receptors are
      encouraging and may provide some hope for patients with pancreatic cancer.

PMID- 15155138
TI  - Emerging drugs for head and neck cancer.
AB  - Head and neck squamous cell carcinoma is a devastating disease with poor outcomes
      in advanced stages. For patients with locally advanced disease, a multi-modality
      approach with chemotherapy and radiotherapy has been used. Despite advances in
      diagnosis and treatment, including improvements in radiation therapy, surgical
      techniques, chemotherapy and prevention strategies, survival rates for patients
      with recurrent head and neck cancer are poor. Several cytotoxic drugs with
      significant activities as single agents and/or combination regimens have shown
      high response rates, but over the past several years, significant improvement in
      survival has not been achieved. New drugs, including those that target the
      epidermal growth factor receptor, the p53 gene, RAS protein post-translational
      modification, the proteosome, vascular endothelial growth factor, cyclooxygenase
      2 and other molecular pathways, are promising agents in the management of head
      and neck cancer. Their potential is being tested in various settings, including
      chemoprevention, recurrent and metastatic disease and combination with radiation
      therapy and/or cytotoxic agents.

PMID- 15155139
TI  - Emerging DNA topisomerase inhibitors as anticancer drugs.
AB  - Drugs that inhibit or poison the function of topoisomerase (topo) enzymes are one
      of the mainstays of cancer chemotherapy, and include some of the most widely used
      anticancer drugs. A major effort is going into improving the broad deficiencies
      of established agents: for topo I inhibitors, this includes better lactone
      stability than for camptothecin; for topo II inhibitors lower cardiotoxicity than
      for existing anthracycline/anthraquinone analogues and for both classes, ways to
      counteract cell efflux mechanisms. At the same time, new types of structures are
      also being explored and developed. This review covers 24 drugs (6 topo I
      inhibitors, 12 topo II inhibitors and 6 dual topo I/II inhibitors) at various
      stages of clinical development. Although many of the latter class are at an early
      stage of development, despite a lack of detailed structural biology on the target
      enzymes, the research area is vigorous and has the potential to open up specific
      new drug design approaches.

PMID- 15155140
TI  - Histone modification enzymes: novel targets for cancer drugs.
AB  - In eukaryotes, genomic DNA is packaged with histone proteins into the cell
      nucleus as chromatin, condensing the DNA > 10,000-fold. Chromatin is highly
      dynamic and exerts profound control on gene expression. Localised chromatin
      decondensation facilitates access of nuclear machinery. Chromatin displays
      epigenetic inheritance, in that changes in its structure can pass to the next
      generation independently of the DNA sequence itself. It is now clear that the
      post-translational modification of histones, for example, acetylation,
      methylation and phosphorylation, plays a crucial role in the regulation of
      nuclear function through the 'histone code'. There has been significant progress
      in identifying and understanding the enzymes that control these complex
      processes, in particular histone acetyltransferases and histone deacetylases. The
      exciting discovery that compounds inhibiting histone deacetylase activity also
      have antitumour properties has focused attention on their use as anticancer
      drugs. As a consequence, there is ongoing evaluation of several histone
      deacetylase inhibitor compounds in Phase I and II clinical trials with promising
      early results. It is likely that many of the enzymes involved in the control of
      histone modification will provide therapeutic opportunities for the treatment of
      cancer, including histone methyltransferases and Aurora kinases.

PMID- 15155141
TI  - Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP
      IV inhibitors.
AB  - Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates
      insulin secretion and protects beta-cells, inhibits glucagon secretion and
      gastric emptying, and reduces appetite and food intake. In agreement with these
      actions, it has been shown to be highly effective in the treatment of Type 2
      diabetes, causing marked improvements in glycaemic profile, insulin sensitivity
      and beta-cell performance, as well as weight reduction. The hormone is
      metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and,
      therefore, cannot be easily used clinically. Instead, resistant analogues of the
      hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV
      inhibitors, which have been demonstrated to protect the endogenous hormone and
      enhance its activity. Agonists include both albumin-bound analogues of GLP-1 and
      exendin-4, a lizard peptide. Clinical studies with exendin have been carried out
      for > 6 months and have indicated efficacy in patients inadequately treated with
      oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once
      daily administration, have demonstrated similar efficacy. Diabetes therapy, based
      on GLP-1 receptor activation, therefore, appears very promising.

PMID- 15155142
TI  - Emerging drugs for endometriosis.
AB  - Medical treatment of endometriosis relies on drugs that suppress ovarian steroids
      and induce an hypoestrogenic state that causes atrophy of ectopic endometrium.
      Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and
      oestrogen-progestin combinations have all proven effective in relieving pain and
      reducing the extent of endometriotic implants. However, symptoms often recur
      after discontinuation of therapy and hypoestrogenism-related side effects limit
      the long-term use of most medications. Furthermore, these therapies are of
      limited value in patients with a desire to become pregnant because they inhibit
      ovulation. An important target for current research is to identify effective
      therapies that can be safely administered in the long term. GnRH analogues with
      add-back therapy, progestogens and continuous oral contraceptive are options
      available for a medium or long-term systemic treatment. Mifepristone, an
      antiprogestogen, may constitute an alternative if encouraging preliminary data on
      its effectiveness and tolerability are confirmed. A very appealing area of
      interest is the possibility of treating endometriosis without suppressing ovarian
      function. Aromatase inhibitors might have such characteristics as they have been
      shown to inhibit oestrogen production selectively in endometriotic lesions,
      without affecting ovarian function; the clinical role of these drugs in the
      treatment of endometriosis is under evaluation. Levonorgestrel medicated
      intrauterine device has proven effective in relieving dysmenorrhoea associated
      with endometriosis, as well as pain associated with rectovaginal endometriosis.
      Although a systemic absorption is present determining side effects, this approach
      is promising in the long-term management of this condition. A fundamental
      objective of research in endometriosis treatment is to develop new therapeutic
      approaches based on the findings from experimental studies on the
      aetiopathogenesis of the disease; current research is focusing on anti
      inflammatory drugs and modulators of the immune system. TNF-binding protein-1 and
      IL-12 have proved effective in reducing endometriotic lesions in animal models,
      while pentoxifylline and INF-alpha 2b have shown encouraging results in clinical
      studies. This area may be of paramount importance in the near future in order to
      develop a therapy that could prevent or eradicate endometriosis rather than
      merely relieving the symptoms.

PMID- 15155144
TI  - Superbugs and Superdrugs: a focus on antibacterials--6th annual SMi conference.

PMID- 15155143
TI  - Emerging oral drugs for erectile dysfunction.
AB  - Erectile dysfunction (ED) is a common medical condition that affects the sexual
      life of millions of men worldwide. Many drugs are now available for the treatment
      of ED, with oral pharmacotherapy representing the first-line option for most
      patients. Sildenafil citrate, an inhibitor of the enzyme phosphodiesterase type 5
      (PDE5), is the most widely prescribed oral agent and has a very satisfactory
      efficacy-safety profile in all patient categories. Tadalafil (Cialis; Eli Lilly &
      Co., ICOS) and vardenafil (Levitra; Bayer Pharmaceuticals, GlaxoSmithKline) are
      new PDE5 inhibitors that have recently been approved worldwide. Both have been
      associated with significant positive efficacy-safety profiles. Apomorphine
      sublingual is a dopamine D1 and D2 receptor agonist, which has been approved for
      marketing in Europe. It is best selected for treating patients with mild-to
      moderate ED, but it is seldom used in clinical practice due to its limited
      efficacy and side effects, particularly nausea. Patients who do not respond to
      oral pharmacotherapy or who are unable to use it are appropriate candidates for
      intracavernosal and intraurethral therapy. The efficacy of second-line treatment
      is high, but the attrition rate remains significant. For the purpose of this
      review, clinical and pharmacological analysis focuses on the recent advances in
      the field of oral therapy, including PDE5 inhibitors and sublingual apomorphine.

PMID- 15155145
TI  - Medication errors resulting from the confusion of drug names.
AB  - If drug names are similar, errors can occur. Problems arise when different drugs
      have similar names (whether proprietary or non-proprietary), when formulations
      with the same brand name contain different drugs, when the same drug is marketed
      in formulations with different names, and when drug names are abbreviated. The
      risk of errors could be reduced by some simple precautions at different stages of
      drug development, prescribing, supply, and administration. Regulatory authorities
      and manufacturers should maintain their vigilance when naming new drugs and
      formulations, and should be prepared to change names if errors occur. Before they
      write an unfamiliar name on a prescription, prescribers should check what they
      are prescribing and what other medications the patient is taking (patients should
      be familiar with their medicines), and pharmacists should check patients'
      medicines. At all times there should be good communication among those who
      prescribe, supply, and administer medicines, and those who take them.

PMID- 15155146
TI  - Leukotriene receptor antagonists--risks and benefits for use in paediatric
      asthma.
AB  - Leukotrienes (LTs) are important mediators of the pathophysiology of asthma,
      specifically, bronchoconstriction, airway inflammation and oedema and mucus
      hypersecretion. The LT receptor antagonists (LTRAs) inhibit these potent effects
      by selectively blocking the cysteinyl LT 1 receptor. These are the first novel
      therapies for asthma since the introduction of inhaled corticosteroids (ICS) in
      1972. Unlike generalised inhibition of airway inflammation by ICS, the LTRAs
      target inhibition of specific mediators. In general, paediatric data concerning
      these agents remain quite limited. However, they have demonstrated efficacy
      against allergen- and exercise-induced bronchospasm in both adults and children.
      Recently, their potential role for the treatment of viral-induced wheeze in young
      children has been explored. In multiple, placebo-controlled trials, the LTRAs
      have demonstrated efficacy for the treatment of mild persistent asthma, additive
      benefit in the management of symptomatic moderate asthmatics on maintenance ICS
      and evidence of significant steroid-sparing. Findings from these clinical trials
      and real-world experience support the use of the LTRAs as controller agents for
      persistent asthma. Based on their excellent safety profiles, tolerance and ease
      of administration (including once daily dosing with montelukast), this drug class
      may offer several important features for use as controller therapy, particularly
      in asthmatic children as young as 1 year of age, however, this must continue to
      be reviewed as new paediatric data become available.

PMID- 15155147
TI  - Safety of rifampin and pyrazinamide for the treatment of latent tuberculosis
      infection.
AB  - A 2-month regimen of rifampin and pyrazinamide (2RZ) became an accepted
      alternative for treatment of latent tuberculosis (TB) after initial studies in
      HIV-seropositive patients demonstrated safety and efficacy. Once this alternative
      came into widespread use, however, a number of cases of severe and fatal
      hepatitis associated with 2RZ were reported. Although the initial experience with
      HIV-seropositive patients was encouraging, subsequent research demonstrated that
      the risk of 2RZ-associated hepatitis is considerably greater than the risk of
      hepatitis associated with isoniazid treatment for latent TB. Updated guidelines
      now recommend only restricted use of the 2RZ regimen for latent TB, with careful
      supervision.

PMID- 15155148
TI  - Adverse effects of antiretroviral therapy: focus on bone density.
AB  - Osteopenia and osteoporosis are the most important bone disorders affecting
      patients with HIV infection. The available data indicate that HIV-infected
      patients have a high prevalence of low bone mineral density. Reduced bone mass
      and alterations of bone metabolism have been found in HIV-infected children,
      adolescents and adults. The variety and complexity of changes in bone metabolism
      in patients with HIV infection and the different possible mechanisms triggering
      bone mineral loss, as well as the different stages of disease and cumulative
      exposure to antiretroviral drugs at the time of clinical evaluation, may
      contribute to the wide range of mineral loss observed and to the uncertainty of
      the role of specific antiretroviral medications.

PMID- 15155149
TI  - Psychotic symptoms in Parkinson's disease: pathophysiology and management.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disease, in which mainly
      dopaminergic neurons in the substantia nigra in the brain degenerate, leading to
      a depletion of dopamine (DA) in the striatum. The most important motor
      disturbances of the disease are bradykinesia (slowing down of movement),
      hypokinesia (poverty of movement), rigidity (muscle stiffness), tremor and
      postural instability. Besides these well-known motor symptoms, non-motor symptoms
      may develop, such as depression, cognitive impairment and psychosis. Psychotic
      symptoms constitute a relatively common but nevertheless serious complication,
      with visual hallucinations and paranoid delusions often being most prominent.
      These symptoms are important contributors to patient and caregiver distress and
      are often important risk factors for nursing home placement. Exogenous (related
      to therapeutic interventions) factors are of major importance but endogenous
      (related to the disease process itself) factors might also contribute to the
      development of psychotic symptoms in PD. Therapeutic strategies comprise
      reduction of antiparkinsonian treatment, cholinesterase inhibitors and atypical
      antipsychotics. As psychotic symptoms in PD are often influenced by both
      endogenous and exogenous factors, a combination of strategies may be chosen.

PMID- 15155150
TI  - The pharmacology of bipolar disorder during pregnancy and breastfeeding.
AB  - Treating bipolar disorder in women during reproduction presents a significant
      challenge to the physician. The pharmaceutical agents most commonly used for
      treating bipolar disorder have been associated with adverse effects when used
      during pregnancy and breastfeeding. Of particular concern has been the
      association of lithium with cardiac malformations, and the association of
      carbamazepine and valproate with neural tube defects including spina bifida.
      Toxicity in neonates has also been reported for the most commonly used mood
      stabilising agents. Treatment options for mood stabilisation are either
      associated with risks of adverse events, have been used less frequently and their
      associated risks are unknown, or may not provide effective prophylaxis against
      recurrences of bipolar episodes. However, strategies are available that minimise
      the risk to the fetus and infant whilst still providing effective prophylaxis
      against bipolar disorder in the mother. Ideally, a treatment regimen tailored to
      suit the individual should consider both mother and baby and should be planned
      prior to conception.

PMID- 15155151
TI  - Risk-benefit of antiemetics in prevention and treatment of chemotherapy-induced
      nausea and vomiting.
AB  - The development of effective antiemetic prophylaxis is one of the most
      significant steps forward in the area of supportive care. Fifteen years ago,
      patients receiving chemotherapy had to face the fact that nausea and vomiting
      were inevitable adverse effects, which could only be partially prevented by
      treatment with antiemetics such as dopamine (DA) D2 receptor antagonists and
      corticosteroids. The first group of drugs specifically developed as antiemetics
      was the serotonin (5-hydroxytryptamine [5-HT](3)) receptor antagonists. These
      drugs have dramatically improved prophylaxis of chemotherapy-induced emesis,
      particularly when used in combination with a corticosteroid. This combination has
      resulted in a significant decrease in the number of patients vomiting, whereas
      the improvement in the prophylaxis of nausea has been less successful. Another
      group of antiemetics, the neurokinin (NK) 1 receptor antagonists, has recently
      been developed, and the first drug in this class, aprepitant, has been approved
      by the FDA and the EU authorities. Studies have showed that patients benefit from
      the use of this drug in combination with standard antiemetic therapy (5-HT 3
      receptor antagonist plus a corticosteroid), both in the acute and delayed phase
      of nausea and vomiting induced by cisplatin-based chemotherapy. This development
      has not only led to improved efficacy but also to a decreased risk associated
      with the use of antiemetics. One of the problems with traditional antiemetics,
      for example, the DA D2 receptor antagonists, is the risk of unpleasant adverse
      effects including restlessness and dystonic reactions. To avoid these adverse
      effects, combination with benzodiazepines or antihistamines was necessary, often
      resulting in sedation. Modern research also includes pharmacogenomic
      investigations. This has led to speculation about the importance of drug-drug
      interactions involving antiemetics through competition for metabolism by the
      cytochrome P450 isoenzymes. The worst possible interaction would be a decrease in
      the effect of different cytotoxins but there is no evidence that such
      interactions are of importance in daily clinical practice. Guidelines are useful
      tools in the optimisation of antiemetic prophylaxis but, unfortunately,
      implementation of the evidence-based recommendations is far from successful. A
      prerequisite for further optimisation of antiemetic prophylaxis is updating of
      the guidelines, including recommendations for the use of NK 1 receptor
      antagonists (aprepitant), followed by implementation of these recommendations in
      the clinic. Future research must include 'the difficult trials' focusing on the
      remaining groups of patients with severe chemotherapy-induced nausea and
      vomiting, including patients with refractory and breakthrough emesis.

PMID- 15155152
TI  - Drugs and the retina.
AB  - The retina is relatively protected from systemic drug administration because of
      the blood-retinal barrier, a highly selective mechanism adapted to providing a
      regulated homeostatic environment for this highly specialised tissue. However, a
      number of drugs have been associated with retinal toxicity. Vigabatrin, as an
      adjunctive therapy for the management of partial epilepsy, is associated with
      visual field defects in approximately 40% of patients. Hydroxychloroquine, used
      in the treatment of rheumatoid arthritis and systemic lupus erythematosus, is
      also associated with a retinopathy. In view of this, ophthalmological screening
      and monitoring is recommended during prescription of both of these drugs. In
      these cases, the retina is the site for an adverse drug reaction and the dose of
      therapy may be important in determining the likelihood of retinal toxicity.
      However, in the case of cytomegalovirus retinitis, the retina is the intended
      site for pharmacological action. The treatment of this condition with the
      antiviral agents ganciclovir, valganciclovir, foscarnet and cidofovir, can also
      be associated with significant systemic toxicity.

PMID- 15155153
TI  - Production of therapeutic proteins in fungal hosts.

PMID- 15155154
TI  - Modulation of immune responses - strategies for optimising vaccines.
AB  - Over decades, vaccination has considerably reduced the morbidity and mortality
      caused by infectious pathogens. Efficient vaccines conferring long-term
      protection have been developed despite a minimal understanding of the specific
      immunological mechanisms involved in this protection. Recent technological
      advances have provided valuable insights into host-pathogen interactions and
      considerably improved our knowledge of the effector and regulatory mechanisms
      behind the innate and adaptive immune responses. With the ability to initiate and
      manipulate immune responses, it is now possible to develop and optimise safe and
      effective vaccination strategies using a more rational approach.

PMID- 15155155
TI  - Stem cell bioengineering for regenerative medicine.
AB  - Stem cells can be used to treat a variety of diseases and several recent studies
      in animal models demonstrate the potential of bioengineering strategies targeting
      adult and embryonic stem cells. In order to obtain the desired cells for
      transplantation, stem cell bioengineering approaches entail the manipulation of
      environmental signals influencing cell survival, proliferation, self-renewal and
      differentiation. In that regard, multivariate analytical approaches have been
      used with success to optimise different stem cell culture processes. The genetic
      or molecular enhancement of stem cells is also a powerful means to control their
      proliferation or differentiation or to correct genetic defects in recipients. In
      the future, systems-level approaches have the potential to revolutionise the
      field of stem cell bioengineering by improving our understanding of regulatory
      networks controlling cellular behaviour. This advance in basic biology will be
      instrumental for the implementation of many stem cell-based regenerative
      therapies at the clinical level, as treatment accessibility will depend on the
      development of robust technologies to produce sufficient cell numbers.

PMID- 15155156
TI  - The therapeutic potential of stem cells in the treatment of craniofacial
      abnormalities.
AB  - Anomalies associated with the vertebrate head and face account for a third of all
      reported major birth defects. Of the principle cell populations that participate
      in formation of the craniofacial complex, the neural crest is central, generating
      much of the peripheral nervous system and constituting the predominant connective
      tissue-forming mesenchyme of the facial skeleton. Many craniofacial anomalies
      are, therefore, largely attributed to defects in neural crest cell development.
      Neural crest cells exhibit many of the features of stem cells; they are
      multipotent, remarkably plastic and have a limited capacity for self-renewal.
      This article will review recent studies that demonstrate the ability of stem
      cells to generate neural crest cell populations that form appropriate neural
      crest derivatives in the developing craniofacial complex, and will discuss the
      potential application for stem cells in the treatment of craniofacial disorders.

PMID- 15155157
TI  - Development of novel tissue engineering scaffolds via electrospinning.
AB  - Electrospinning has recently been developed as an efficient technique to develop
      polymeric nanofibres. Various synthetic and natural biodegradable polymers have
      been electrospun into fibres with diameters in the nanometre range (< 1 microm).
      The fibre diameter, structure and physical properties of the nanofibre matrices
      can be effectively tuned by controlling various parameters that affect the
      electrospinning process. The dimension and structure of electrospun polymeric
      nanofibre mats resembles mostly the collagen phase of natural extracellular
      matrix. This, combined with excellent physical properties such as high surface
      area, high porosity, interconnective pores of the nanofibre matrices and
      appropriate mechanical properties, well-controlled degradation rates and
      biocompatibility of the base polymer, make biodegradable polymeric nanofibre
      matrices ideal candidates for developing scaffolds for tissue engineering. This
      article reviews the recent advances in the development of synthetic biodegradable
      nanofibre-based matrices as scaffolds for tissue engineering.

PMID- 15155158
TI  - Delivery of transgenically modified adult bone marrow cells to the rodent central
      nervous system.
AB  - A major challenge in the treatment of neurological disorders is the effective
      delivery of molecules into the CNS and, more so, to the lesion site. The blood
      brain barrier restricts the delivery of therapeutic molecules into the CNS when
      injected intravenously. This difficulty is further compounded by the short half
      life of certain therapeutic agents. Organ-targeted protein delivery could
      circumvent these difficulties, provided that the corresponding cDNA can be
      delivered and expressed in the target tissue effectively and safely. Recent
      studies from a number of laboratories indicate that a subset of adult bone marrow
      cells home to the CNS among other organs and can be engineered to deliver and
      express therapeutic proteins into the CNS. This article, which is focused on work
      from the authors' research, reviews the opportunities and difficulties presented
      by this approach.

PMID- 15155159
TI  - Strategies for long-term gene expression in the skin to treat metabolic
      disorders.
AB  - Due to its accessibility, size and contact with the blood circulation, the skin
      is an attractive target for somatic gene therapy. Permanent cutaneous expression
      can be achieved by genetic manipulation of epidermal keratinocytes ex vivo
      followed by transplantation or by local injection of viral vectors. Furthermore,
      progress is being made to develop topical gene transfer methods leading to
      permanent gene expression. There is experimental evidence showing that
      genetically engineered skin can produce and secrete medically relevant proteins
      to the circulation and also produce enzymes that can clear metabolites
      accumulating in various diseases. Thus, cutaneous gene transfer approaches may be
      relevant not only for local skin diseases, but also for certain systemic
      disorders.

PMID- 15155160
TI  - Tissue-specific promoters for cancer gene therapy.
AB  - Adenoviral cancer gene therapy approaches have resulted in promising recent
      results. Following only a decade of intense development, some of the crucial
      obstacles are now being overcome. Insufficient transduction has been the main
      limitation of earlier approaches. A new approach for increasing transduction of
      tumour cells is utilisation of replication-competent oncolytic agents, such as
      conditionally replicating adenoviruses (CRADs). The anti-tumour effect is caused
      by replication of the virus per se and, thus, replication must be restricted to
      tumour cells to protect normal tissues from damage. Tissue-specific promoters
      (TSPs) represent a powerful tool for decreasing the toxicity of cancer gene
      therapy to normal tissues and have previously been utilised for specific mutation
      compensation or delivery of prodrug-converting enzymes. However, TSPs can also be
      used for controlling crucial viral replication regulators and consequent
      restriction of replication to tumour cells. Initial clinical trials have
      demonstrated the safety and suggested efficacy for TSP-controlled CRADs as a
      novel approach for cancer gene therapy.

PMID- 15155161
TI  - Vaccination with T cell-defined antigens.
AB  - Tumour immunology encompasses a broad array of biological phenomena including
      interactions between neoplastic cells and the innate and adaptive immune
      response. Among immune cells, T cells have taken the centre stage because they
      can be easily demonstrated to specifically recognise autologous cancer cells. As
      most tumour-associated antigens are intracellular proteins, T cells appear to be
      the most suitable tool for cancer-specific attack, as antibodies do not cross the
      cell membrane and the innate immune response lacks the same level of specificity.
      Finally, the relative ease in which T cells can be educated through antigen
      specific immunisation to recognise cancer cells has elevated them to an even
      higher stature. In this review, it will be argued that T cells represent a unique
      anticancer agent, characterised by absolute specificity. Although other
      therapeutic modalities (antibody-based) have been effectively implemented, a
      comparison of T cell-based approaches with other modalities goes beyond the
      purposes of this review and will not be included in the discussion. However, it
      is obvious that the role of the T cell is limited and other components of the
      immune response (effector mononuclear phagocytes, natural killer cells,
      cytokines, chemokines, soluble factors), genetic background and tumour
      heterogeneity are likely to be necessary for the completion of cancer rejection.

PMID- 15155162
TI  - The role of cell culture vaccines in the control of the next influenza pandemic.
AB  - Pandemic influenza A viruses of avian origin are of particular concern and have
      crossed the species barrier several times in recent years, giving rise to illness
      and occasionally death in humans. This situation could become dramatically worse
      if the infectivity of avian viruses for humans were increased by reassortment
      between the genes of human and avian viruses. Co-infection of humans or an
      intermediate host with an avian strain and an existing human strain could produce
      new viruses of unknown pathogenicity to which the entire population would be
      susceptible. Inactivated vaccines against influenza have been prepared for many
      years using viruses grown in embryonated chicken eggs. However, the use of eggs
      presents difficulties when vaccine supplies need to be expanded at short notice.
      It seems likely that future vaccines will be prepared in high-yielding cell
      cultures from continuous lines that are preferably anchorage-independent. At
      present, only certain preparations of the Vero and Madin-Darby canine kidney cell
      lines, grown and maintained in serum-free medium, are acceptable to all
      regulatory authorities. However, this situation is likely to change with
      increasing need for non-pandemic and pandemic vaccines.

PMID- 15155163
TI  - Plant-derived vaccines against diarrhoeal diseases.
AB  - Transgenic plant-derived vaccines offer a new strategy for the development of
      safe, inexpensive vaccines against diarrhoeal diseases. In animal and Phase I
      clinical studies, these vaccines have been safe and immunogenic without the need
      for a buffer or vehicle other than the plant cell. This review examines some
      early attempts to develop oral transgenic plant vaccines against enteric
      infections such as enterotoxigenic Escherichia coli infection, cholera and
      norovirus infection.

PMID- 15155164
TI  - Daclizumab induction in solid organ transplantation.
AB  - Antibody induction therapy is used in solid organ transplantation to prevent
      rejection in the early postoperative period. It is especially useful in high-risk
      groups such as retransplants, patients with delayed graft function to delay the
      initiation of nephrotoxic calcineurin inhibitors (tacrolimus, cyclosporin),
      highly sensitised recipients and African-American recipients. Historically,
      antibody induction has been associated with a high incidence of adverse effects
      and a complicated administration regimen. Daclizumab is a monoclonal antibody
      that exerts its effect by binding to the alpha subunit (CD25) of the human
      interleukin (IL)-2 receptor on the surface of activated lymphocytes, thus
      preventing the binding of IL-2. It is used for induction therapy and is well
      tolerated with easy administration. Although originally studied as a five-dose
      regimen, there is a growing accumulation of data that fewer doses (two or three)
      are efficacious and less costly for preventing rejection.

PMID- 15155165
TI  - The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in
      orthopaedic applications.
AB  - Preclinical proof-of-concept, feasibility and efficacy studies in lower animals
      resulted in the accumulation of data that served as a backbone for clinical
      trials with the recombinant, osteogenic bone morphogenetic protein-2 (BMP-2).
      Among the important observations was the dependence of dose and carrier on the
      outcome for osseous union in relation to the animal model used. Clinical outcome
      data for spinal applications indicate better overall results compared with
      traditional controls that utilised autogenous iliac crest bone graft for fusion.
      Parameters include less blood loss, less operating room time and costs, better
      fusion outcomes and increased patient satisfaction. At this juncture, the long
      journey from the identification of BMP-2 in demineralised bone fraction to FDA
      approval for use in a singular orthopaedic application has been completed. It has
      been demonstrated to be safe, efficacious and cost-effective, leading to
      increased patient satisfaction and improved clinical outcome.

PMID- 15155166
TI  - Keystone symposia - stem cells.
AB  - The Keystone Symposia stem cell conference focused on the biological nature of
      self-renewing cell populations that exist in special regulatory niches and form
      other cell types that enable maintenance of tissue function, repair and, in some
      cases, regeneration. Adult stem cells are present in most, if not all tissues,
      and their regulation as renewing populations, the nature of the niche and the
      factors driving decisions for differentiation in primary pathways remain the
      dominant interest in the field. The more vexed question concerning possible
      transdifferentiation of adult stem cells from one tissue type to another has
      become focused on the role of fusion and whether this is a recapitulation of
      normal processes in embryonic and adult development. The possible linkage of
      cancer phenotypes with stem cells and downstream progenitor cell types through
      loss of regulatory influences in renewal, expansion and lineage commitment is a
      rapidly growing interest. Pluripotent embryonic stem (ES) cells and their
      maintenance and directed differentiation into a variety of tissue types remains
      an optimistic field of research in which some debate exists about true
      pluripotency of adult stem cells. The role of epigenetic influences on
      differentiation and development has drawn on data from nuclear transfer studies
      in cloning the whole organism and in ES cell production. The formation of germ
      cells and their renewal and differentiation was also a major interest of the
      symposium.

PMID- 15155167
TI  - Movement-produced feedback as a mechanism for the temporal anticipation of motor
      responses.
AB  - That part of the input hypothesis of motor timing behavior which postulates that
      movement-produced feedback can serve as a mechanism for the temporal anticipation
      of motor responses was tested. 32 male college Ss temporally anticipated (no
      preview) the coincidence of a moving pointer with a stationary one and executed
      the timing response with his right hand while either a high (HFB) or low (LFB)
      level of movement-produced feedback was indirectly manipulated in the left arm.
      The HFB group temporally anticipated with greater accuracy than the LFB group
      which supported that part of the input hypothesis being tested. Apparently, Ss
      were relying on proprioceptive feedback about the position of their left arm
      movement to cue the timing response of their right hand.

PMID- 15155168
TI  - Motor performance and response consistency as a function of age.
AB  - The specificity versus generality of motor performance and motor response
      consistency ws investigated as a function of age. 120 Ss, 30 each at age 7, 11,
      15 and 19 yr., were given 120 practice trials (60 trials per session with 24 hr.
      interpolated between sessions) on both simple and choice RT tasks. For motor
      performance the reliability of individual differences were high in both tasks at
      all ages, while the amount of generality was moderately high in the two younger
      groups but diminished with age. The reliability coefficients for motor response
      consistency were low for both tasks but, with two exceptions, statistically
      significant. There was no evidences for generality in motor response consistency
      at any age.

PMID- 15155169
TI  - A closed-loop theory of motor learning.
AB  - Following a discussion of the meaning of the term "skills" and a review of
      historical influences on their learning, a closed-loop theory for learning simple
      movements is presented. Empirical generalizations from the literature are stated,
      and the theory is used to explain them. The generalizations are of 2 classes:
      learning through the application of knowledge of results, and the effects of
      withdrawing knowledge of results.

PMID- 15155170
TI  - Anxiety and motor behavior: a review.
AB  - Anxiety and related terms were defined by conceptually distinguishing between
      "state" and "trait" anxiety and between anxiety, stress and fear. The literature
      concerned with the anxiety-motor behavior relationship was reviewed using the
      state-trait anxiety distinction. After outlining the general notions of drive
      theory as related between the Taylor Manifest Anxiety Scale (MAS) and motor
      behavior in the absence or in the presence of a stressor, and on those studies
      using anxiety scales other than MAS. The accumulated evidence failed to reveal
      any consistent trends in these three areas. The use of drive theory and the MAS
      to predict motor behavior ws shown not to be a viable approach. Two alternative
      approaches were briefly outlined.

PMID- 15155171
TI  - Reactions to "anxiety and motor behavior".
AB  - Martens has presented and excellent and provocative paper in an extremely
      interesting area. He has certainly outlined most of the complexities of anxiety,
      discussed the limitations and strengths of various theoretical approaches to its
      study, and has presented alternatives to existing methods. My approach has been
      to try to summarize what I have held to be the major problem ares or limiting
      factors in the study of state anxiety (stress) and motor performance and then
      incorporate these problem areas into the context of Marten's conclusions.

PMID- 15155172
TI  - Two factors to be considered in the design of experiments in anxiety and motor
      behavior.
AB  - There are two aspects of Martens' paper which deserve comment. The first deals
      with experimental design and statistical power while the second concerns the
      distinction between performance and learning and the implications it has for
      research in anxiety and motor learning.

PMID- 15155173
TI  - What can you say about a twenty-year old theory that won't die?
AB  - Stillbirth is the usual fate of theories whose empirical implications at
      conception are not borne out by actual test. Theories which receive some degree
      of experimental confirmation, however modest, typically continue to exist as long
      as there is an interest in the phenomena to which they address themselves or
      until they are displaced by a more attractive theory.

PMID- 15155174
TI  - An outline of a theory of action systems.
AB  - It is argued that the traditional psychological construal of the distinction
      between central ("open loop") and peripheral ("closed loop") neural processes is
      no longer tenable. A review of the relevant psychobiological research on the
      control of movement shows that both the central-peripheral dichotomy and the
      distinction between sensory and motor systems derived from that dichotomy are
      incompatible with what is known about the processes underlying action. Based on
      experimental and comparative data, a new theory of action is proposed. The basic
      concept of this new theory is the action system: Unlike motor systems, action
      systems involve sensory as well as motor processes; action systems are not
      organized into response hierarchies, but rather in coalitional structures of
      adjustable movements and postures. The phylogeny of action systems is discussed,
      and the eight most important action systems are distinguished in terms of their
      evolved distinctive functions. The difficulties of developing a taxonomy of
      actions for functionally specific types of behavior made up of that can be
      controlled is resolved by showing how kinds of action are differentiated by the
      kinds of affordances their components help to realize.

PMID- 15155175
TI  - Correlation of movement patterns via pattern recognition.
AB  - A structural pattern recognition method for the quantitative determination of
      equivalence or similarity between movement patterns was examined. A chain
      encoding technique was implemented for the analysis of lower limb trajectories
      during walking and running. Conjoint angular displacement or angular velocity
      patterns provided kinematic data which were cross-correlated to determine
      geometric congruity of within and between subject motor patterns. The
      correlations of the movement patterns during different speeds of locomotion
      revealed numerical coefficients which consistently and quantitatively
      discriminated the similarity or dissimilarity of limb movement patterns.

PMID- 15155176
TI  - Vision and proprioception in simple catching.
AB  - Articular proprioception is normally considered to provide accurate information
      about limb position, particularly in ball skills in which the eyes are be
      occupied with tracking the ball. If this is so, then preventing sight of the
      catching hand without interfering with visual tracking of the ball should affect
      the accuracy of catching. The experiment reported here indicates that is not the
      case. Catching is much less accurate if the hand cannot be seen. The errors made
      are in positioning of the catching hand, which frequently does not contact the
      ball. In addition, subjects showed larger changes in the felt length arms after
      catching without sight of the hand than did those who could hand while catching.
      Visual information about the position of the hand for catching, and this may be
      because the proprioceptive system is by vision.

PMID- 15155177
TI  - The role of visual monitoring in observational learning of action patterns:
      making the unobservable observable.
AB  - The present experiment tested the hypothesis that concurrent visual feedback
      enhances observational learning of a novel action pattern that normally would be
      unobservable. Subjects repeatedly enacted a modeled action pattern with visual
      monitoring of their reproductions throughout enactments, during only early or
      late phases of enactment, or not at all. At periodic intervals the adequacy of
      their conception of the modeled pattern was also measured. Visual feedback during
      ongoing performance enhanced accurate reproduction of the modeled pattern; the
      facilitative effect was most pronounced for reproduction of complex response
      components. The superiority of subjects who had enacted these difficult response
      components with visual feedback was maintained even when both the model and
      feedback were withdrawn. Visual feedback did not facilitate accurate enactment of
      the modeled pattern before development of an adequate cognitive representation of
      it. The results support the social learning view that observationally-learned
      behaviors are cognitively represented and that visual monitoring serves to
      decrease discrepancies between conception and action.

PMID- 15155178
TI  - Foxl1 null mice have abnormal intestinal epithelia, postnatal growth retardation,
      and defective intestinal glucose uptake.
AB  - Mice lacking the mesenchymal winged helix transcription factor Foxl1 exhibit
      markedly abnormal small intestinal epithelia and postnatal growth retardation. We
      investigated whether defects in intestinal nutrient uptake and specific transport
      processes exist in mice homozygous for a Foxl1 null allele (Foxl1-/-). Foxl1-/-
      mice and controls on a defined genetic background were weighed regularly and
      killed at 2, 4, and 12 wk of age. Intestinal uptake studies, quantitative real
      time PCR, RNase protection assays, and Western blot analyses were performed.
      Foxl1-/- mice have dysmorphic small intestinal epithelia and postnatal growth
      retardation. Foxl1-/- mice demonstrate decreased small intestinal uptake of D
      glucose in all age groups studied. Intestinal uptake of D-fructose and two amino
      acids, L-proline and L-leucine, is not altered. Consistent with these findings,
      Foxl1-/- mice show decreased levels of the intestinal D-glucose transporter
      SGLT1. Expression of sucrase-isomaltase, lactase, GLUT2, and Na+-K+ ATPase are
      not changed. Foxl1-/- mice demonstrate markedly abnormal intestinal epithelia,
      postnatal growth retardation, and decreased intestinal uptake of D-glucose. The
      specific effect of Foxl1 on intestinal d-glucose uptake is due to decreased
      production of SGLT1 protein in the small intestine. Thus we identified, for the
      first time, a link between a mesenchymal factor, Foxl1, and the regulation of a
      specific epithelial transport process.

PMID- 15155179
TI  - Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in
      C. parvum-infected porcine ileum.
AB  - Cell culture models implicate increased nitric oxide (NO) synthesis as a cause of
      mucosal hyperpermeability in intestinal epithelial infection. NO may also mediate
      a multitude of subepithelial events, including activation of cyclooxygenases. We
      examined whether NO promotes barrier function via prostaglandin synthesis using
      Cryptosporidium parvum-infected ileal epithelium in residence with an intact
      submucosa. Expression of NO synthase (NOS) isoforms was examined by real-time RT
      PCR of ileal mucosa from control and C. parvum-infected piglets. The isoforms
      mediating and mechanism of NO action on barrier function were assessed by
      measuring transepithelial resistance (TER) and eicosanoid synthesis by ileal
      mucosa mounted in Ussing chambers in the presence of selective and nonselective
      NOS inhibitors and after rescue with exogenous prostaglandins. C. parvum
      infection results in induction of mucosal inducible NOS (iNOS), increased
      synthesis of NO and PGE2, and increased mucosal permeability. Nonselective
      inhibition of NOS (NG-nitro-L-arginine methyl ester) inhibited prostaglandin
      synthesis, resulting in further increases in paracellular permeability. Baseline
      permeability was restored in the absence of NO by exogenous PGE2. Selective
      inhibition of iNOS [L-N6-(1-iminoethyl)-L-lysine] accounted for approximately 50%
      of NOS-dependent PGE2 synthesis and TER. Using an entire intestinal mucosa, we
      have demonstrated for the first time that NO serves as a proximal mediator of
      PGE2 synthesis and barrier function in C. parvum infection. Expression of iNOS by
      infected mucosa was without detriment to overall barrier function and may serve
      to promote clearance of infected enterocytes.

PMID- 15155180
TI  - Recommendations for treatment of human infections caused by Bartonella species.

PMID- 15155181
TI  - The magnitude of the association between fluoroquinolone use and quinolone
      resistant Escherichia coli and Klebsiella pneumoniae may be lower than previously
      reported.
AB  - Case-control analyses of resistant versus susceptible isolates have implicated
      fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant
      isolates of Enterobacteriaceae. We suspect that such methodology may overestimate
      this association. A total of 84 cases with fluoroquinolone-resistant isolates and
      578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or
      Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel
      multivariable analyses. For comparison of previous estimates, the results of 10
      published case-control studies of risk for fluoroquinolone resistance in isolates
      of Enterobacteriaceae were pooled by using a random-effects model. Exposure to
      fluoroquinolones was significantly positively associated with fluoroquinolone
      resistance (odds ratio [OR], 3.17) and negatively associated with fluoroquinolone
      susceptibility (OR, 0.18). Multivariable analyses yielded similar estimates (ORs,
      2.04 and 0.10, respectively). As data on antibiotic exposure were limited to
      inpatient prescriptions, misclassification of fluoroquinolone exposure in persons
      who received fluoroquinolones as outpatients may have led to an underestimation
      of the true effect size. Pooling the results of previously published studies in
      which a direct comparison of fluoroquinolone-resistant and fluoroquinolone
      susceptible cases was used resulted in a markedly higher effect estimate (OR,
      18.7). Had we directly compared resistant and susceptible cases, our univariate
      OR for the association between fluoroquinolone use and the isolation of resistant
      Enterobacteriaceae would have been 19.3, and the multivariate OR would have been
      16.5. Fluoroquinolone use is significantly associated with the isolation of
      fluoroquinolone-resistant Enterobacteriaceae; however, previous studies likely
      exaggerated the magnitude of this association.

PMID- 15155182
TI  - Determination of the in vivo pharmacodynamic profile of cefepime against extended
      spectrum-beta-lactamase-producing Escherichia coli at various inocula.
AB  - Cefepime was evaluated in vivo against two inoculum sizes of four strains of
      Escherichia coli that produced extended-spectrum beta-lactamases (ESBLs) in a
      murine neutropenic thigh infection model to characterize the pharmacodynamic
      activity of cefepime in the presence of ESBL-producing bacteria and to evaluate
      if differences in lengths of cefepime exposure are required with various inocula.
      Three strains possessed a single enzyme each: TEM-10, TEM-12, and TEM-26. The
      fourth strain possessed two TEM-derived ESBLs and a third uncharacterized enzyme.
      Two non-ESBL-producing E. coli strains were included for comparison. Mice
      received various doses of cefepime to achieve a spectrum of percentages of time
      the drug was above the MIC (%T>MICs) for each isolate at both inocula. No
      significant difference in cefepime exposure was required to achieve similar
      bactericidal effects for ESBL- and non-ESBL-producing isolates when the starting
      inoculum was 10(5) CFU of E. coli per thigh. The increased MICs observed in vitro
      for the ESBL-producing strains at 10(7) CFU/ml did not predict the amount of
      exposure required to achieve a comparable level of bactericidal activity in vivo
      at the corresponding starting inoculum of 10(7) CFU/thigh. Compared to the
      cefepime exposure in tests with the lower inoculum (10(5) CFU/thigh), less
      exposure was required when the starting inoculum was 10(7) CFU/thigh (%T>MIC, 6%
      versus 26%), such that similar doses (in milligrams per kilogram of body weight)
      produced similar bactericidal effects with both inocula of ESBL-producing
      isolates. Equivalent exposures of cefepime produced similar effects against the
      microorganisms regardless of the presence of ESBL production. Pharmacodynamic
      profiling undertaken with conventional cefepime MIC determinations predicted in
      vivo microbial outcomes at both inoculum sizes for the ESBL-producing isolates
      evaluated in this study. These data support the use of conventional MIC
      determinations in the pharmacodynamic assessment of cefepime.

PMID- 15155183
TI  - Effectiveness of ciprofloxacin, levofloxacin, or moxifloxacin for treatment of
      experimental Staphylococcus aureus keratitis.
AB  - The purpose of this study was to quantitatively compare, in a rabbit keratitis
      model, the levels of effectiveness of moxifloxacin, levofloxacin, and
      ciprofloxacin for the treatment of Staphylococcus aureus isolates of diverse
      antibiotic susceptibilities. Rabbit eyes were intrastromally injected with
      approximately 100 CFU of methicillin-sensitive or methicillin-resistant S. aureus
      (MSSA or MRSA, respectively) organisms that were either sensitive or resistant to
      ofloxacin. One drop of moxifloxacin (0.5%), levofloxacin (0.5%), or ciprofloxacin
      (0.3%) was topically applied hourly from 4 to 9 (early) or 10 to 15 (late) h
      postinfection. At 1 h after cessation of therapy, the corneas were harvested, and
      the number of CFU per cornea was determined. For the ofloxacin-sensitive strains,
      early treatment of MSSA or MRSA with moxifloxacin, levofloxacin, or ciprofloxacin
      produced approximately a 5-log decrease in CFU per cornea relative to that in
      untreated eyes (P </= 0.0001). For late therapy of ofloxacin-sensitive strains,
      moxifloxacin, levofloxacin, and ciprofloxacin produced approximately 5-, 4-, and
      2- to 3-log reductions in CFU per cornea, respectively (P </= 0.0001). Early
      treatment of the ofloxacin-resistant strains with either moxifloxacin or
      levofloxacin produced a >/=4-log or >/=3-log decrease, respectively, in the MSSA
      or MRSA strains (P </= 0.0001), whereas ciprofloxacin treatment produced a 1-log
      decrease in CFU per cornea relative to that in untreated eyes (P = 0.1540). For
      late treatment of ofloxacin-resistant strains, levofloxacin and ciprofloxacin
      failed to significantly reduce the number of CFU per cornea (P >/= 0.3627),
      whereas moxifloxacin produced a significant reduction in CFU per cornea of
      approximately 1 log (P </= 0.0194). Therefore, for three of the four treatments
      tested, moxifloxacin demonstrated greater effectiveness than either levofloxacin
      or ciprofloxacin.

PMID- 15155184
TI  - tcaA inactivation increases glycopeptide resistance in Staphylococcus aureus.
AB  - The experimental deletion of the tcaRAB region has been shown to increase
      teicoplanin resistance in Staphylococcus aureus. By sequential genetic
      complementation of a tcaRAB mutant, we identified tcaA as the key gene within
      tcaRAB that is responsible for changes in glycopeptide resistance levels.
      Northern blot analysis of the tcaRAB region showed that the tcaA gene is
      expressed only weakly over the growth cycle and is strongly inducible by
      teicoplanin. Among some clinical isolates tested, glycopeptide-intermediate
      resistant (GISA) strains Michigan and SA137/93G were found to have truncated tcaA
      genes. While the former carries a nucleotide insertion that creates a premature
      stop codon, the latter was found to harbor an IS256 insertion. Complementation of
      these two GISA strains with a functional tcaA allele reduced their levels of
      teicoplanin and vancomycin resistance five- to eightfold and twofold,
      respectively. The data presented here indicate that inactivation of tcaA
      contributes to and plays a relevant role in glycopeptide resistance in S. aureus
      clinical isolates.

PMID- 15155185
TI  - Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains
      producing a novel class a beta-lactamase, GES-3, in a neonatal intensive care
      unit in Japan.
AB  - Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad
      spectrum cephalosporins, was isolated from the neonatal intensive care unit
      (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain
      KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and
      sequence analysis revealed that production of a novel extended-spectrum class A
      beta-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions
      of M62T and E104K on the basis of the sequence of GES-1, was responsible for
      resistance in strain KG525 and its transconjugant. The bla(GES-3) gene was
      located as the first gene cassette in a class 1 integron that also contained an
      aacA1-orfG fused gene cassette and one unique cassette that has not been
      described in other class 1 integrons and ended with a truncated 3' conserved
      segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae
      strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from
      different neonates during a 1-year period in the same NICU where strain KG525 had
      been isolated, were also positive for GES-type beta-lactamase genes by PCR.
      Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic
      consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae
      strains. Southern hybridization analysis with a GES-type beta-lactamase gene
      specific probe showed that the locations of bla(GES) were multiple and diverse
      among the six strains. These findings suggest that within the NICU setting
      genetically related K. pneumoniae strains carrying the bla(GES) gene were
      ambushed with genetic rearrangements that caused the multiplication and
      translocation of the bla(GES) gene.

PMID- 15155186
TI  - Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci
      by inhibiting its efflux from bacterial cells.
AB  - Epigallocatechin-gallate (EGCg), the major catechin present in green tea
      extracts, has been shown to have several antibacterial activities, limiting
      bacterial growth and invasion and acting in synergy with beta-lactam antibiotics.
      In this article, we report that EGCg at doses half and below its calculated MIC
      of 100 microg/ml, is able to reverse tetracycline resistance in staphylococcal
      isolates expressing the specific efflux pump Tet(K) and appears to improve the
      MICs of tetracycline for susceptible staphylococcal isolates as well. The visible
      effect of EGCg is an increased accumulation of tetracycline inside bacterial
      cells. This effect is likely due to the inhibition of pump activity, and it is
      evident not only for Tet(K) pumps but also for efflux pumps of a different class
      [Tet(B)]. In summary, our data indicate that the observed dramatic enhancement by
      EGCg of tetracycline activity for resistant staphylococcal isolates is caused by
      impairment of tetracycline efflux pump activity and increased intracellular
      retention of the drug, suggesting a possible use of EGCg as an adjuvant in
      antibacterial therapy.

PMID- 15155187
TI  - Anti-inflammatory effects of moxifloxacin on activated human monocytic cells:
      inhibition of NF-kappaB and mitogen-activated protein kinase activation and of
      synthesis of proinflammatory cytokines.
AB  - We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory
      effects in immunosuppressed mice infected with Candida albicans by inhibiting
      interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) production in
      the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)
      kappaB translocation in lung epithelium and macrophages in MXF-treated mice. In
      the present study we investigated the effects of MXF on the production of
      proinflammatory cytokines (i.e., IL-8, TNF-alpha, and IL-1beta) by activated
      human peripheral blood monocytes and THP-1 cells and analyzed the effects of the
      drug on the major signal transduction pathways associated with inflammation: NF
      kappaB and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase
      (JNK). The levels of IL-8, TNF-alpha, and IL-1beta secretion rose 20- and 6.7
      fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells,
      respectively. MXF (5 to 20 microg/ml) significantly inhibited cytokine production
      by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively. In THP-1
      cells, the level of NF-kappaB nuclear translocation increased fourfold following
      stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited
      (38%) by 10 microg of MXF per ml. We then assayed the degradation of inhibitor
      (I)-kappaB by Western blotting. LPS-PMA induced degradation of I-kappaB by 73%,
      while addition of MXF (5 microg/ml) inhibited I-kappaB degradation by 49%.
      Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA
      and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10
      microg/ml). We conclude that MXF suppresses the secretion of proinflammatory
      cytokines in human monocytes and THP-1 cells and that it exerts its anti
      inflammatory effects in THP-1 cells by inhibiting NF-kappaB, ERK, and JNK
      activation. Its anti-inflammatory properties should be further assessed in
      clinical settings.

PMID- 15155188
TI  - The action of bismuth against Helicobacter pylori mimics but is not caused by
      intracellular iron deprivation.
AB  - Helicobacter pylori is highly susceptible to bismuth, a heavy metal with
      antimicrobial activity linked to its effect on bacterial iron uptake. Three
      strains of H. pylori were analyzed for indicators of iron limitation following
      exposure to the MIC of colloidal bismuth subcitrate (MIC(CBS)). Similar
      morphologic and outer membrane changes were observed following growth in iron
      limiting medium and at the MIC(CBS) that inhibited the growth of all three
      strains. These changes, which were also observed for iron-limited bacteria, were
      alleviated by the addition of iron to the cultures. H. pylori ATP levels, reduced
      in iron-limiting medium, were below the limits of detection in two of the three
      strains following exposure to bismuth. The addition of iron partially restored
      bacterial ATP levels in these two strains, although not to normal concentrations.
      In contrast, exposure of the same strains to the MIC(CBS) failed to deplete
      intracellular levels of iron, which were significantly reduced by culturing in
      iron-limiting medium. Thus, the antimicrobial effect of bismuth and of iron
      limitation on H. pylori may be similar. However, the respective mechanisms of
      intracellular action would appear to be mediated by different pathways within the
      cell.

PMID- 15155189
TI  - Reactivity of platelia Aspergillus galactomannan antigen with piperacillin
      tazobactam: clinical implications based on achievable concentrations in serum.
AB  - The possible reactivities of commonly used antibiotics of fungal, nonfungal, and
      nonmicrobial or synthetic sources with the Platelia Aspergillus galactomannan
      assay were assessed. For drugs that tested positive, the minimal concentration of
      the antibiotic in serum that yielded a positive test (index, >0.5) was
      determined. At undiluted concentrations, piperacillin and multiple lots of
      piperacillin-tazobactam tested positive, whereas amoxicillin, ampicillin
      sulbactam, nafcillin, cefazolin, ceftazidime, erythromycin, gentamicin, and
      levofloxacin tested negative. All three lots of piperacillin-tazobactam and all
      bags within each lot tested positive, with a mean index value of 5.168. At
      achievable concentrations in serum, however, only one of three lots of
      piperacillin-tazobactam yielded a positive test. Concentrations of 75, 150, and
      300 microg/ml of serum tested positive with the Platelia Aspergillus enzyme
      immunoassay, whereas lower concentrations, mimicking the trough levels, tested
      negative. Thus, while achievable serum piperacillin-tazobactam concentrations may
      potentially result in a positive test for galactomannan, the timing of the
      collection of serum samples from patients may influence the test results, with
      reactivity being less likely in samples collected at trough levels or prior to
      the administration of a dose of the antibiotic.

PMID- 15155190
TI  - Mercury inactivates transcription and the generalized transcription factor TFB in
      the archaeon Sulfolobus solfataricus.
AB  - Mercury has a long history as an antimicrobial agent effective against eukaryotic
      and prokaryotic organisms. Despite its prolonged use, the basis for mercury
      toxicity in prokaryotes is not well understood. Archaea, like bacteria, are
      prokaryotes but they use a simplified version of the eukaryotic transcription
      apparatus. This study examined the mechanism of mercury toxicity to the archaeal
      prokaryote Sulfolobus solfataricus. In vivo challenge with mercuric chloride
      instantaneously blocked cell division, eliciting a cytostatic response at
      submicromolar concentrations and a cytocidal response at micromolar
      concentrations. The cytostatic response was accompanied by a 70% reduction in
      bulk RNA synthesis and elevated rates of degradation of several transcripts,
      including tfb-1, tfb-2, and lacS. Whole-cell extracts prepared from mercuric
      chloride-treated cells or from cell extracts treated in vitro failed to support
      in vitro transcription of 16S rRNAp and lacSp promoters. Extract-mixing
      experiments with treated and untreated extracts excluded the occurrence of
      negative-acting factors in the mercury-treated cell extracts. Addition of
      transcription factor B (TFB), a general transcription factor homolog of
      eukaryotic TFIIB, to mercury-treated cell extracts restored >50% of in vitro
      transcription activity. Consistent with this finding, mercuric ion treatment of
      TFB in vitro inactivated its ability to restore the in vitro transcription
      activity of TFB-immunodepleted cell extracts. These findings indicate that the
      toxicity of mercuric ion in S. solfataricus is in part the consequence of
      transcription inhibition due to TFB-1 inactivation.

PMID- 15155191
TI  - Susceptibility of Candida species to photodynamic effects of photofrin.
AB  - The in vitro susceptibility of pathogenic Candida species to the photodynamic
      effects of the clinically approved photosensitizing agent Photofrin was examined.
      Internalization of Photofrin by Candida was confirmed by confocal fluorescence
      microscopy, and the degree of uptake was dependent on incubation concentration.
      Uptake of Photofrin by Candida and subsequent sensitivity to irradiation was
      influenced by culture conditions. Photofrin uptake was poor in C. albicans
      blastoconidia grown in nutrient broth. However, conversion of blastoconidia to
      filamentous forms by incubation in defined tissue culture medium resulted in
      substantial Photofrin uptake. Under conditions where Photofrin was effectively
      taken up by Candida, irradiated organisms were damaged in a drug dose- and light
      dependent manner. Uptake of Photofrin was not inhibited by azide, indicating that
      the mechanism of uptake was not dependent on energy provided via electron
      transport. Fungal damage induced by Photofrin-mediated photodynamic therapy (PDT)
      was determined by evaluation of metabolic activity after irradiation. A strain of
      C. glabrata took up Photofrin poorly and was resistant to killing after
      irradiation. In contrast, two different strains of C. albicans displayed
      comparable levels of sensitivity to PDT. Furthermore, a reference strain of C.
      krusei that is relatively resistant to fluconazole compared to C. albicans was
      equally sensitive to C. albicans at Photofrin concentrations of >/=3 microg/ml.
      The results indicate that photodynamic therapy may be a useful adjunct or
      alternative to current anti-Candida therapeutic modalities, particularly for
      superficial infections on surfaces amenable to illumination.

PMID- 15155192
TI  - In vitro interactions between amphotericin B, itraconazole, and flucytosine
      against 21 clinical Aspergillus isolates determined by two drug interaction
      models.
AB  - Combination therapy of flucytosine (5FC) with other antifungal agents could be of
      use for the treatment of invasive aspergillosis. However, interpretation of the
      results of in vitro interactions is problematic. The fractional inhibitory
      concentration (FIC) index is the most commonly used method, but it has several
      major drawbacks in characterizing antifungal drug interaction. Alternatively, a
      response surface approach using the concentration-effect relationship over the
      whole concentration range instead of just the MIC can be used. We determined the
      in vitro interactions between amphotericin B (AMB), itraconazole, and 5FC against
      21 Aspergillus isolates with a broth microdilution checkerboard method that
      employs the dye MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
      bromide]. FIC indices based on three different MIC endpoints (MIC-0, MIC-1, and
      MIC-2) and the interaction coefficient alpha were determined, the latter by
      estimation from the response surface approach described by Greco et al. (W. R.
      Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995). The value
      obtained for the FIC index was found to be dependent on the MIC endpoint used and
      could be either synergistic, indifferent, or antagonistic. The response surface
      approach gave more consistent results. Of the three combinations tested, the AMB
      5FC combination was the most potent in vitro against Aspergillus spp. We conclude
      that the use of the response surface approach for the interpretation of in vitro
      interaction studies of antifungals may be helpful in order to predict the nature
      and intensity of the drug interaction. However, the correlation of these results
      with clinical outcome remains difficult and needs to be further investigated.

PMID- 15155193
TI  - Effects of voriconazole on Cryptococcus neoformans.
AB  - Voriconazole is a broad-spectrum triazole that offers extended activity against
      molds and yeasts that are not susceptible to earlier azole-type drugs. Recent
      studies indicate that melanization can severely reduce the susceptibility of
      certain antifungal drugs, but there is no information as to whether voriconazole
      is vulnerable to this effect. The activity of voriconazole on C. neoformans was
      assessed by MIC analysis and time-kill assays for melanized and nonmelanized
      cells. Cell morphology, capsule release, and phagocytosis of C. neoformans were
      studied in the presence or absence of subinhibitory concentrations of
      voriconazole. Voriconazole was fungicidal at concentrations of >/=8 microg/ml in
      vitro against the strains of C. neoformans examined, and its efficacy was not
      diminished by melanization. Cells grown in subinhibitory concentrations of
      voriconazole had smaller cellular and capsular volumes than cells grown in the
      absence of drug. The induction of the capsule by serum was not affected by
      voriconazole. Cells grown in subinhibitory concentrations of voriconazole
      released their capsule and were phagocytosed at rates comparable with yeast grown
      without the antifungal. The high activity of voriconazole against both melanized
      and nonmelanized cells results suggest that voriconazole may be a particularly
      valuable drug for cryptococcosis.

PMID- 15155194
TI  - Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of
      anidulafungin in invasive candidiasis and candidemia.
AB  - This study evaluated the safety and efficacy of anidulafungin, a novel
      echinocandin, in patients with invasive candidiasis, including candidemia. A
      total of 123 eligible patients were randomized to one of three intravenous
      regimens, 50, 75, or 100 mg once daily. Treatment continued for 2 weeks beyond
      resolution or improvement of signs and symptoms. The primary efficacy criterion
      was a successful global response rate (i.e., clinical and microbiological
      success) in the evaluable population at the follow-up (FU) visit, 2 weeks after
      end of therapy (EOT). One hundred twenty (120) patients received at least one
      dose of anidulafungin; 68 were evaluable. Review of adverse events and laboratory
      data indicated no dose response for safety parameters. Non-albicans Candida
      species accounted for approximately one-half of all isolates. Success rates at
      EOT were 84, 90, and 89% in the 50-, 75-, and 100-mg groups, respectively. At FU,
      the success rates were 72, 85, and 83%. Phase 3 studies of anidulafungin for the
      treatment of invasive candidiasis and candidemia are warranted.

PMID- 15155196
TI  - Tn2009, a Tn916-like element containing mef(E) in Streptococcus pneumoniae.
AB  - The association between the macrolide efflux gene mef(E) and the tet(M) gene was
      studied in two clinical strains of Streptococcus pneumoniae that belonged to
      serotypes 19F and 6A, respectively, and that were resistant to both tetracycline
      and erythromycin. The mef(E)-carrying element mega (macrolide efflux genetic
      assembly; 5,511 bp) was found to be inserted into a Tn916-like genetic element
      present in the chromosomes of the two pneumococcal strains. In both strains, mega
      was integrated at the same site, an open reading frame identical to orf6 of
      Tn916. The new composite element, Tn2009, was about 23.5 kb and, with the
      exception of the tet(M)-coding sequence, appeared to be identical in both
      strains. By sequencing of the junction fragments of Tn2009 at the site of
      insertion into the chromosome, it was possible to show that (i) the insertion
      site was identical in the two clinical strains and (ii) the integration of Tn2009
      caused a 9.5 kb-deletion in the pneumococcal chromosome. It was not possible to
      detect the conjugal transfer of Tn2009 to a recipient pneumococcal strain;
      however, transfer of the whole element by transformation was shown to occur. It
      is possible to hypothesize that Tn2009 relies on transformation for its spread
      among clinical strains of S. pneumoniae.

PMID- 15155195
TI  - Candidate topical microbicides bind herpes simplex virus glycoprotein B and
      prevent viral entry and cell-to-cell spread.
AB  - Topical microbicides designed to prevent acquisition of sexually transmitted
      infections are urgently needed. Nonoxynol-9, the only commercially available
      spermicide, damages epithelium and may enhance human immunodeficiency virus
      transmission. The observation that herpes simplex virus (HSV) and human
      immunodeficiency virus bind heparan sulfate provided the rationale for the
      development of sulfated or sulfonated polymers as topical agents. Although
      several of the polymers have advanced to clinical trials, the spectrum and
      mechanism of anti-HSV activity and the effects on soluble mediators of
      inflammation have not been evaluated. The present studies address these gaps. The
      results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, and
      polymethylenehydroquinone sulfonate inhibit HSV infection 10,000-fold and are
      active against clinical isolates, including an acyclovir-resistant variant. The
      compounds formed stable complexes with glycoprotein B and inhibit viral binding,
      entry, and cell-to-cell spread. The effects may be long lasting due to the high
      affinity and stability of the sulfated compound-virus complex, as evidenced by
      surface plasmon resonance studies. The candidate microbicides retained their
      antiviral activities in the presence of cervical secretions and over a broad pH
      range. There was little reduction in cell viability following repeated exposure
      of human endocervical cells to these compounds, although a reduction in secretory
      leukocyte protease inhibitor levels was observed. These studies support further
      development and rigorous evaluation of these candidate microbicides.

PMID- 15155197
TI  - Biochemical characterization of the naturally occurring oxacillinase OXA-50 of
      Pseudomonas aeruginosa.
AB  - The bla(OXA-50) gene (formerly known as the PA5514 gene) is an oxacillinase gene
      identified in silico in the genome of Pseudomonas aeruginosa PAO1. By using a
      mutant strain of P. aeruginosa PAO1 that had an inactivated bla(AmpC)
      cephalosporinase gene, the bla(OXA-50) gene was shown to be expressed
      constitutively in P. aeruginosa. This beta-lactamase gene was cloned onto a
      multicopy plasmid and expressed in P. aeruginosa and Escherichia coli. It
      conferred decreased susceptibility to ampicillin and ticarcillin and,
      interestingly, to moxalactam and meropenem in P. aeruginosa but not in E. coli.
      Overexpression and purification enabled us to determine the molecular mass (25
      kDa), the pI value (8.6), and the hydrolysis spectrum of the OXA-50 beta
      lactamase. It is a narrow-spectrum oxacillinase that uncommonly hydrolyzes
      imipenem, although at a low level. Very similar oxacillinase genes were
      identified in all P. aeruginosa isolates from various geographical origins
      tested. The weak variability of the nucleotide sequence of this gene (0 to 2%)
      corresponded to that found for the naturally occurring bla(AmpC) cephalosporinase
      gene of P. aeruginosa. The study indicated that P. aeruginosa harbors two
      naturally encoded beta-lactamase genes, one of which encodes an inducible
      cephalosporinase and the other of which encodes a constitutively expressed
      oxacillinase.

PMID- 15155199
TI  - Comparative activities of the triterpene saponin maesabalide III and liposomal
      amphotericin B (AmBisome) against Leishmania donovani in hamsters.
AB  - Maesabalide III (MB-III), an oleane triterpene saponin isolated from the
      Vietnamese plant Maesa balansae, is a new antileishmanial lead compound whose
      activity against Leishmania donovani (MHOM/ET/67/L82) in groups of five golden
      hamsters was evaluated after administration of a single subcutaneous dose on
      either day 1 (prophylactic treatment) or day 28 (curative treatment) after
      infection. Liposomal amphotericin B (AmBisome), administered intravenously at 5
      mg/kg of body weight, was used as the reference drug. Amastigote burdens in
      liver, spleen, and bone marrow were determined either 7 days (early effects) or
      56 days (late effects) after treatment. Prophylactic administration of MB-III at
      0.2 mg/kg reduced liver amastigote burdens by 99.8 and 83% within 7 and 56 days
      after treatment, respectively. In the latter group, however, all animals became
      ill and some died. Both MB-III at 0.8 mg/kg and liposomal amphotericin B were
      100% effective against liver stages, but clearance from the spleen and bone
      marrow was not achieved. Curative administration of MB-III at 0.2 and 0.4 mg/kg
      was not protective, as no survivors were left at the termination of the
      experiment on day 84. Despite the high level of reduction of the liver amastigote
      burden after treatment with MB-III at 0.8 mg/kg (94.2%) or liposomal amphotericin
      B (99.4%), clinical protection could not be obtained in either group, with two
      deaths occurring and the residual liver burdens persisting. It is concluded that
      administration of a single dose of MB-III at 0.8 mg/kg has efficacy potential
      comparable to that of a single dose of liposomal amphotericin B at 5 mg/kg and is
      therefore considered a promising new antileishmanial lead compound. However,
      multiple-dose pharmacological, toxicological, and pharmacokinetic studies are
      still needed before it can become a valid drug candidate for development.

PMID- 15155198
TI  - Antimicrobial activities of garenoxacin (BMS 284756) against Asia-Pacific region
      clinical isolates from the SENTRY program, 1999 to 2001.
AB  - Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested
      in the SENTRY Program for susceptibility to six fluoroquinolones including
      garenoxacin. Garenoxacin was four- to eightfold less active against
      Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar
      percentages at 1 microg/ml. Garenoxacin was more active against gram-positive
      species than all other fluoroquinolones except gemifloxacin. For Staphylococcus
      aureus, oxacillin resistance was high in many participating countries (Japan,
      67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels
      of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA).
      Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4
      microg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin
      nonsusceptibility and macrolide resistance were high in many countries. No
      relationship was seen between penicillin and garenoxacin susceptibility, with all
      isolates being susceptible at <2 microg/ml. There was, however, a partial
      correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin
      resistant isolates for which garenoxacin MICs were 0.25 to 1 microg/liter,
      mutations in both the ParC and GyrA regions of the quinolone resistance
      determining region could be demonstrated. No mutations conferring high-level
      resistance were detected. Garenoxacin shows useful activity against a wide range
      of organisms from the Asia-Pacific region. In particular, it has good activity
      against S. aureus and S. pneumoniae, although there is evidence that low-level
      resistance is present in those organisms with ciprofloxacin resistance.

PMID- 15155200
TI  - Novel pharmacokinetic-pharmacodynamic model for prediction of outcomes with an
      extended-release formulation of ciprofloxacin.
AB  - The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has
      been compared to that of the immediate-release (IR) product in healthy
      volunteers. The only significant difference in pharmacokinetic parameters between
      the two formulations was seen in the rate constant of absorption, which was
      approximately 50% greater with the IR formulation. The geometric mean plasma
      ciprofloxacin concentrations were applied to an in vitro pharmacokinetic
      pharmacodynamic model exposing three different clinical strains of Escherichia
      coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in
      plasma. A novel mathematical model was derived to describe the time course of
      bacterial CFU, including capacity-limited replication and first-order rate of
      bacterial clearance, and to model the effects of ciprofloxacin concentrations on
      these processes. A "mixture model" was employed which allowed as many as three
      bacterial subpopulations to describe the total bacterial load at any moment.
      Comparing the two formulations at equivalent daily doses, the rates and extents
      of bacterial killing were similar with the IR and XR formulations at MICs of 0.03
      and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR
      formulation showed a moderate advantage in antibacterial effect: the area under
      the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h
      log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for
      XR were 4.54 and 3.13, respectively. The mathematical model explained the
      differences in bacterial killing rate for two regimens with identical AUC/MIC
      ratios.

PMID- 15155201
TI  - Genetic environments of the rmtA gene in Pseudomonas aeruginosa clinical
      isolates.
AB  - Nine Pseudomonas aeruginosa strains showing very high levels of resistance to
      various aminoglycosides have been isolated from clinical specimens in seven
      separate Japanese hospitals in five prefectures since 1997. These strains harbor
      the newly identified 16S rRNA methylase gene (rmtA). When an rmtA gene probe was
      hybridized with genomic DNAs of the nine strains digested with EcoRI, two
      distinct patterns were observed. The 11.1- and 15.8-kb regions containing the
      rmtA genes of strains AR-2 and AR-11, respectively, were sequenced and compared.
      In strain AR-2, a transposase gene-like sequence (sequence 1) and a probable tRNA
      ribosyltransferase gene (orfA) were located upstream of rmtA, and a Na(+)/H(+)
      antiporter gene-like sequence (sequence 2) was identified downstream of rmtA.
      This 6.2-kbp insert (the rmtA locus) was flanked by 262-bp kappagamma elements.
      Part of the orfQ gene adjacent to an inverted repeat was found outside of the
      rmtA locus. In strain AR-11, the rmtA gene and sequence 2 were found, but the 5'
      end of the orfA gene was truncated and replaced with IS6100. An orfQ-orfI region
      was present on each side of the rmtA gene in strain AR-11. The G+C content of the
      rmtA gene was about 55%, and since the newly identified rmtA gene may well be
      mediated by some mobile genetic elements such as Tn5041, further dissemination of
      the rmtA gene could become an actual clinical problem in the near future.

PMID- 15155203
TI  - In vitro activities of garenoxacin and levofloxacin against Chlamydia pneumoniae
      are not affected by presence of Mycoplasma DNA.
AB  - We studied 20 Chlamydia pneumoniae isolates obtained from respiratory sites and
      atheroma tissue of patients from various geographic areas to determine the
      susceptibilities of these isolates to a new des-fluoroquinolone, garenoxacin, and
      to levofloxacin. In addition, we assessed the cultures with these isolates by PCR
      for the presence or absence of Mycoplasma sp. DNA. Both the MIC at which 90% of
      isolates are inhibited (MIC(90)) and the minimal bactericidal concentration at
      which 90% of isolates are killed (MBC(90)) for garenoxacin were 0.06 microg/ml,
      and both the MIC(90) and the MBC(90) for levofloxacin were 2.0 microg/ml. The
      activity of garenoxacin against C. pneumoniae was 32-fold greater than that of
      levofloxacin. Mycoplasma sp. DNA was detected by PCR in 17 of 20 cultures.
      Mycoplasma amplicons from five Mycoplasma DNA-positive C. pneumoniae cultures
      were sequenced and found to represent four Mycoplasma species. Our data
      demonstrate that C. pneumoniae cultures frequently contain Mycoplasma DNA and
      that its presence in C. pneumoniae cultures does not appear to affect the
      susceptibility results for the two fluoroquinolones that we tested.

PMID- 15155202
TI  - Spread of novel aminoglycoside resistance gene aac(6')-Iad among Acinetobacter
      clinical isolates in Japan.
AB  - A novel aminoglycoside resistance gene, aac(6')-Iad, encoding aminoglycoside 6'-N
      acetyltransferase, was identified in Acinetobacter genospecies 3 strain A-51. The
      gene encoded a 144-amino-acid protein, which shared modest identity (up to 36.7%)
      with some of the aminoglycoside 6'-N-acetyltransferases. The results of high
      pressure liquid chromatography assays confirmed that the protein is a functional
      aminoglycoside 6'-N-acetyltransferase. The enzyme conferred resistance to
      amikacin, tobramycin, sisomicin, and isepamicin but not to gentamicin. The
      prevalence of this gene among Acinetobacter clinical isolates in Japan was then
      investigated. Of 264 Acinetobacter sp. strains isolated from geographically
      diverse areas in Japan in 2002, 16 were not susceptible to amikacin, and aac(6')
      Iad was detected in 7. Five of the producers of aminoglycoside 6'-N
      acetyltransferase type Iad were identified as Acinetobacter baumannii, and two
      were identified as Acinetobacter genospecies 3. These results suggest that
      aac(6')-Iad plays a substantial role in amikacin resistance among Acinetobacter
      spp. in Japan.

PMID- 15155204
TI  - alpha-Galactosylceramide and novel synthetic glycolipids directly induce the
      innate host defense pathway and have direct activity against hepatitis B and C
      viruses.
AB  - alpha-Galactosylceramide is a glycolipid derived from marine sponges that is
      currently in human clinical trials as an anticancer agent. It has also been shown
      to be effective in reducing the amount of hepatitis B virus (HBV) DNA detected in
      mice that produce HBV constitutively from a transgene. It was assumed that all of
      the antiviral and antitumor activities associated with alpha-galactosylceramide
      were mediated through the activation of NK T cells. However, we report here an
      additional unpredicted activity of alpha-galactosylceramide as a direct antiviral
      agent and inducer of the innate host defense pathway. To exploit this activity,
      we have developed a new class of smaller, orally available glycolipids that also
      induce the innate host defense pathway and have direct activity against HBV and
      hepatitis C virus.

PMID- 15155205
TI  - Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated
      human immunodeficiency virus-infected patients.
AB  - The aim of the present study was to assess the pharmacokinetic behavior of
      atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate
      (DF) in human immunodeficiency virus (HIV)-infected patients. Eleven patients
      enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS
      Research, Paris, France) trial 107 were included in this pharmacokinetic study.
      They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from
      day 1 to the end of study. For the first 2 weeks, their nucleoside analog reverse
      transcriptase inhibitor (NRTI) treatments remained unchanged. Tenofovir DF was
      administered QD from day 15 to the end of the study. Ongoing NRTIs were selected
      according to the reverse transcriptase genotype of the HIV isolates from each
      patient. The values of the pharmacokinetic parameters for atazanavir and
      ritonavir were measured before (day 14 [week 2]) and after (day 42 [week 6])
      initiation of tenofovir DF and are reported for the 10 patients who completed the
      study. There was a significant decrease in the area under the concentration-time
      curve from 0 to 24 h (AUC(0-24)) for atazanavir with the addition of tenofovir DF
      (AUC(0-24) ratio, 0.75; 90% confidence interval, 0.58 to 0.97; P = 0.05). There
      was a trend for a decrease in the minimum concentrations of atazanavir and
      ritonavir in plasma when they were combined with tenofovir, but none of the
      differences reached statistical significance. The median decreases in the HIV RNA
      loads at week 2 and week 6 were 0.1 and 0.2 log copies/ml, respectively. In
      summary, our data are consistent with the existence of a significant interaction
      between atazanavir and tenofovir DF.

PMID- 15155206
TI  - Antibacterial activities of the cathelicidins prophenin (residues 62 to 79) and
      LL-37 in the presence of a lung surfactant preparation.
AB  - The antibacterial activities of the cathelicidin peptides LL-37 and an 18-residue
      C-terminal fragment of prophenin, corresponding to positions 62 to 79 of native
      prophenin (PF-18), were analyzed in the presence of a modified surfactant
      preparation isolated from minced porcine lungs. At low micromolar concentrations,
      both LL-37 and PF-18 showed significant activities against different serotypes of
      group B streptococci, with LL-37 being more active on a molar basis. The
      surfactant preparation at a concentration of 10 mg/ml partly blocked the
      antibacterial activity of 9 microM LL-37 and completely blocked the antibacterial
      activity of 9 microM PF-18. However, 10 mg of the surfactant preparation per ml
      had only minor inhibitory effects on LL-37 and PF-18 at 90 microM. Addition of up
      to 900 microM PF-18 did not affect the surface properties of the surfactant
      preparation. These data suggest that surfactant preparations containing
      antimicrobial peptides could be useful for the local treatment of pulmonary
      infections.

PMID- 15155207
TI  - High prevalence of antimicrobial resistance among clinical Streptococcus
      pneumoniae isolates in Asia (an ANSORP study).
AB  - A total of 685 clinical Streptococcus pneumoniae isolates from patients with
      pneumococcal diseases were collected from 14 centers in 11 Asian countries from
      January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14
      antimicrobial agents were determined by the broth microdilution test. Among the
      isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were
      intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates
      from Vietnam showed the highest prevalence of penicillin resistance (71.4%),
      followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The
      penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter
      among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of
      erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%),
      Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin
      were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore,
      Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of
      ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the
      Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the
      spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the
      major reasons for the rapid increases in antimicrobial resistance among S.
      pneumoniae isolates in Asia. Data from the multinational surveillance study
      clearly documented distinctive increases in the prevalence rates and the levels
      of antimicrobial resistance among S. pneumoniae isolates in many Asian countries,
      which are among the highest in the world published to date.

PMID- 15155208
TI  - Ciprofloxacin dimers target gyrase in Streptococcus pneumoniae.
AB  - We have examined the antipneumococcal activities of novel quinolone dimers in
      which ciprofloxacin was tethered to itself or to pipemidic acid by linkage of C-7
      piperazinyl rings. Symmetric 2,6-lutidinyl- and trans-butenyl-linked
      ciprofloxacin dimers (dimers 1 and 2, respectively) and a pipemidic acid
      ciprofloxacin dimer (dimer 3) had activities against Streptococcus pneumoniae
      strain 7785 that were comparable to that of ciprofloxacin, i.e., MICs of 2, 1,
      and 4 to 8 microg/ml versus an MIC of 1 to 2 microg/ml, respectively.
      Surprisingly, unlike ciprofloxacin (which targets topoisomerase IV), several
      lines of evidence revealed that the dimers act through gyrase in S. pneumoniae.
      First, ciprofloxacin-resistant parC mutants of strain 7785 remained susceptible
      to dimers 1 to 3, whereas a gyrA mutation conferred a four- to eightfold increase
      in the dimer MIC but had little effect on ciprofloxacin activity. Second, dimer 1
      selected first-step gyrA (S81Y or S81F) mutants (MICs, 8 to 16 microg/ml) that
      carried wild-type topoisomerase IV parE-parC genes. Third, dimers 1 and 2
      promoted comparable DNA cleavage by S. pneumoniae gyrase and topoisomerase IV,
      whereas ciprofloxacin-mediated cleavage was 10-fold more efficient with
      topoisomerase IV than with gyrase. Fourth, the GyrA S81F and ParC S79F enzymes
      were resistant to dimers, confirming that the resistance phenotype is largely
      silent in parC mutants. Although a dimer molecule could bind very tightly by
      bridging quinolone binding sites in the enzyme-DNA complex, the greater potency
      of ciprofloxacin against gyrase and topoisomerase IV suggests that dimers 1 to 3
      bind in a monomeric fashion. The bulky C-7 side chain may explain dimer targeting
      of gyrase and activity against efflux mutants. Tethered quinolones have potential
      as mechanistic tools and as novel antimicrobial agents.

PMID- 15155209
TI  - Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum.
AB  - The development of resistance to sulfadoxine-pyrimethamine by Plasmodium
      parasites is a major problem for the effective treatment of malaria, especially
      P. falciparum malaria. Although the molecular basis for parasite resistance is
      known, the factors promoting the development and transmission of these resistant
      parasites are less clear. This paper reports the results of a quantitative
      comparison of factors previously hypothesized as important for the development of
      drug resistance, drug dosage, time of treatment, and drug elimination half-life,
      with an in-host dynamics model of P. falciparum malaria in a malaria-naive host.
      The results indicate that the development of drug resistance can be categorized
      into three stages. The first is the selection of existing parasites with genetic
      mutations in the dihydrofolate reductase or dihydropteroate synthetase gene. This
      selection is driven by the long half-life of the sulfadoxine-pyrimethamine
      combination. The second stage involves the selection of parasites with allelic
      types of higher resistance within the host during an infection. The timing of
      treatment relative to initiation of a specific anti-P. falciparum EMP1 immune
      response is an important factor during this stage, as is the treatment dosage.
      During the third stage, clinical treatment failure becomes prevalent as the
      parasites develop sufficient resistance mutations to survive therapeutic doses of
      the drug combination. Therefore, the model output reaffirms the importance of
      correct treatment of confirmed malaria cases in slowing the development of
      parasite resistance to sulfadoxine-pyrimethamine.

PMID- 15155210
TI  - Application of real-time quantitative PCR to molecular analysis of Candida
      albicans strains exhibiting reduced susceptibility to azoles.
AB  - Real-time quantitative PCR was used to measure expression levels of genes
      encoding efflux pumps, ERG11 and two control genes, ACT1 and PMA1, in a
      collection of 14 fluconazole-susceptible Candida albicans isolates. For each
      gene, average expression levels and variations within the population were
      determined. These values were then used as reference points to make predictions
      about the molecular basis of resistance in 38 clinical isolates (the majority of
      which were resistant to fluconazole) obtained from 18 patients treated with
      posaconazole for refractory oropharyngeal candidiasis. For each of the 38
      isolates, the expression levels of genes encoding efflux pumps, ERG11 and the
      control genes, were measured as above. Comparison of the two data sets revealed
      that expression of ACT1 and PMA1 did not vary significantly between the two sets
      of isolates. In contrast, MDR1, ERG11, CDR1, and CDR2 were overexpressed in 3, 4,
      14, and 35, respectively, of the isolates from patients treated with azoles. In
      addition to these changes, the patient isolates all had at least one and often
      multiple missense mutations in ERG11. Select ERG11 alleles were expressed in
      Saccharomyces cerevisiae; all of the alleles tested conferred reduced
      susceptibility to fluconazole. Despite both the increases in pump expression and
      the ERG11 mutations, only one of the patient isolates exhibited a large decrease
      in posaconazole susceptibility.

PMID- 15155211
TI  - Interaction of antimycobacterial drugs with the anti-Mycobacterium avium complex
      effects of antimicrobial effectors, reactive oxygen intermediates, reactive
      nitrogen intermediates, and free fatty acids produced by macrophages.
AB  - The profiles of the interaction of antimycobacterial drugs with macrophage (MPhi)
      antimicrobial mechanisms have yet to be elucidated in detail. We examined the
      effects of various antimycobacterial drugs on the anti-Mycobacterium avium
      complex (MAC) antimicrobial activity of reactive oxygen intermediates (ROIs),
      especially of an H(2)O(2)-halogen (H(2)O(2)-Fe(2+)-NaI)-mediated bactericidal
      system, reactive nitrogen intermediates (RNIs), and free fatty acids (FFAs),
      which are known as central antimicrobial effectors of host MPhis against
      mycobacterial pathogens. We have found that certain drugs, such as rifampin
      (RIF), rifabutin (RFB), isoniazid (INH), clofazimine (CLO), and some
      fluoroquinolones, strongly or moderately reduced the anti-MAC activity of the
      H(2)O(2)-Fe(2+)-NaI system, primarily by inhibiting the generation of hypohalite
      ions and in part by interfering with the halogenation reaction of bacterial cell
      components due to the H(2)O(2)-Fe(2+)-NaI system. This phenomenon is specific to
      the H(2)O(2)-Fe(2+)-NaI system, since these drugs did not reduce the anti-MAC
      activity of RNIs and FFAs. From the perspective of the chemotherapy of MAC
      infections, the present findings indicate an important possibility that certain
      antimycobacterial drugs, such as rifamycins (RIF and RFB), INH, CLO, and also
      some types of fluoroquinolones, may interfere with the ROI-mediated antimicrobial
      mechanisms of host MPhis against intracellular MAC organisms.

PMID- 15155212
TI  - Efficacies of amphotericin B (AMB) lipid complex, AMB colloidal dispersion,
      liposomal AMB, and conventional AMB in treatment of murine coccidioidomycosis.
AB  - The therapeutic efficacy of three lipid formulations of amphotericin B was
      compared with that of conventional amphotericin B in treatment of murine
      coccidioidomycosis. All treatments prolonged survival compared with the no
      treatment group (P < 0.0001). Although conventional amphotericin B was more
      active than lipid formulations on reducing quantitative fungal load on a
      milligram-per-kilogram basis (P < 0.003 to 0.0002), the lipid preparations could
      be administered at higher doses, sterilizing liver and spleen tissues. The
      efficacies of the lipid preparations were similar in this murine model of
      coccidioidomycosis.

PMID- 15155213
TI  - Efficacy of oral ramoplanin for inhibition of intestinal colonization by
      vancomycin-resistant enterococci in mice.
AB  - Ramoplanin is a glycolipodepsipeptide antibiotic with activity against gram
      positive bacteria that is in clinical trials for prevention of vancomycin
      resistant Enterococcus (VRE) bloodstream infections and treatment of Clostridium
      difficile diarrhea. Orally administered ramoplanin suppresses VRE intestinal
      colonization, but recurrences after discontinuation of treatment have frequently
      been observed. We used a mouse model to examine the efficacy of ramoplanin for
      inhibition of VRE colonization and evaluated the etiology of recurrences of
      colonization. Eight days of treatment with ramoplanin (100 microg/ml) in drinking
      water suppressed VRE to undetectable levels, but 100% of mice developed recurrent
      colonization; a higher dose of 500 microg/ml in water was associated with
      recurrent colonization in 50% of mice. Two of eight (25%) mice treated with the
      100-microg/ml dose of ramoplanin had low levels of VRE in their cecal tissues on
      day 8 despite undetectable levels in stool and cecal contents. Mice that received
      prior ramoplanin treatment did not develop VRE overgrowth when challenged with
      10(7) CFU of oral VRE 1, 2, or 4 days later. In communal cages, rapid cross
      transmission and overgrowth of VRE was observed among clindamycin-treated mice;
      ramoplanin treatment effectively suppressed VRE overgrowth in such communal
      cages. Ramoplanin treatment promoted increased density of indigenous
      Enterobacteriaceae and overgrowth of an exogenously administered Klebsiella
      pneumoniae isolate. These results demonstrate the efficacy of ramoplanin for
      inhibition of VRE colonization and suggest that some recurrences occur due to
      reexpansion of organisms that persist within the lining of the colon. Ramoplanin
      treatment may be associated with overgrowth of gram-negative bacilli.

PMID- 15155214
TI  - In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424),
      vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic
      gram-positive species and Corynebacterium spp.
AB  - Telavancin is a new semisynthetic glycopeptide anti-infective with multiple
      mechanisms of action, including inhibition of bacterial membrane phospholipid
      synthesis and inhibition of bacterial cell wall synthesis. We determined the in
      vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin
      dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268
      clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium
      strains using agar dilution methods according to National Committee for Clinical
      Laboratory Standards procedures. Plates with daptomycin were supplemented with
      Ca(2+) to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited
      (MIC(90)s) for telavancin and vancomycin were as follows: Actinomyces spp. (n =
      45), 0.25 and 1 microg/ml, respectively; Clostridium difficile (n = 14), 0.25 and
      1 microg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 microg/ml,
      respectively; Clostridium innocuum (n = 15), 4 and 16 microg/ml, respectively;
      Clostridium clostridioforme (n = 15), 8 and 1 microg/ml, respectively;
      Eubacterium group (n = 33), 0.25 and 2 microg/ml, respectively; Lactobacillus
      spp. (n = 26), 0.5 and 4 microg/ml, respectively; Propionibacterium spp. (n =
      34), 0.125 and 0.5 microg/ml, respectively; Peptostreptococcus spp. (n = 52),
      0.125 and 0.5 microg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03
      and 0.5 microg/ml, respectively. The activity of TD-6424 was similar to that of
      quinupristin-dalfopristin for most strains except C. clostridioforme and
      Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more
      active. Daptomycin had decreased activity (MIC > 4 microg/ml) against 14 strains
      of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus
      plantarum strains. Linezolid showed decreased activity (MIC > 4 microg/ml)
      against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus
      spp. Imipenem and piperacillin-tazobactam were active against >98% of strains.
      The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei
      were >1 microg/ml. The MIC(90) of TD-6424 for all strains tested was </=2
      microg/ml. TD-6424 has potential for use against infections with gram-positive
      anaerobes and deserves further clinical evaluation.

PMID- 15155215
TI  - Omp35, a new Enterobacter aerogenes porin involved in selective susceptibility to
      cephalosporins.
AB  - In Enterobacter aerogenes, beta-lactam resistance often involves a decrease in
      outer membrane permeability induced by modifications of porin synthesis. In ATCC
      15038 strain, we observed a different pattern of porin production associated with
      a variable antibiotic susceptibility. We purified Omp35, which is expressed under
      conditions of low osmolality and analyzed its pore-forming properties in
      artificial membranes. This porin was found to be an OmpF-like protein with high
      conductance values. It showed a noticeably higher conductance compared to Omp36
      and a specific location of WNYT residues in the L3 loop. The importance of the
      constriction region in the porin function suggests that this organization is
      involved in the level of susceptibility to negative large cephalosporins such as
      ceftriaxone by bacteria producing the Omp35 porin subfamily.

PMID- 15155216
TI  - Mutation D30N is not preferentially selected by human immunodeficiency virus type
      1 subtype C in the development of resistance to nelfinavir.
AB  - Differences in baseline polymorphisms between subtypes may result in development
      of diverse mutational pathways during antiretroviral treatment. We compared drug
      resistance in patients with human immunodeficiency virus subtype C (referred to
      herein as "subtype-C-infected patients") versus subtype-B-infected patients
      following protease inhibitor (PI) therapy. Genotype, phenotype, and replication
      capacity (Phenosense; Virologic) were determined. We evaluated 159 subtype-C- and
      65 subtype-B-infected patients failing first PI treatment. Following nelfinavir
      treatment, the unique nelfinavir mutation D30N was substantially less frequent in
      C (7%) than in B (23%; P = 0.03) while L90M was similar (P < 0.5). Significant
      differences were found in the rates of M36I (98 and 36%), L63P (35 and 59%), A71V
      (3 and 32%), V77I (0 and 36%), and I93L (91 and 32%) (0.0001 < P < 0.05) in C and
      B, respectively. Other mutations were L10I/V, K20R, M46I, V82A/I, I84V, N88D, and
      N88S. Subtype C samples with mutation D30N showed a 50% inhibitory concentration
      (IC(50)) change in susceptibility to nelfinavir only. Other mutations increased
      IC(50) correlates to all PIs. Following accumulation of mutations, replication
      capacity of the C virus was reduced from 43% +/- 22% to 22% +/- 15% (P = 0.04).
      We confirmed the selective nature of the D30N mutation in C, and the broader
      cross-resistance of other common protease inhibitor mutations. The rates at which
      these mutational pathways develop differ in C and subtype-B-infected patients
      failing therapy, possibly due to the differential impact of baseline
      polymorphisms. Because mutation D30N is not preferentially selected in nelfinavir
      treated subtype-C-infected patients, as it is in those infected with subtype B,
      the consideration of using this drug initially to preserve future protease
      inhibitor options is less relevant for subtype-C-infected patients.

PMID- 15155217
TI  - Pharmacokinetics and safety of intravenous voriconazole in children after single-
      or multiple-dose administration.
AB  - We conducted a multicenter study of the safety, tolerability, and plasma
      pharmacokinetics of the parenteral formulation of voriconazole in
      immunocompromised pediatric patients (2 to 11 years old). Single doses of 3 or 4
      mg/kg of body weight were administered to six and five children, respectively. In
      the multiple-dose study, 28 patients received loading doses of 6 mg/kg every 12 h
      on day 1, followed by 3 mg/kg every 12 h on day 2 to day 4 and 4 mg/kg every 12 h
      on day 4 to day 8. Standard population pharmacokinetic approaches and generalized
      additive modeling were used to construct the structural pharmacokinetic and
      covariate models used in this analysis. In contrast to that in adult healthy
      volunteers, elimination of voriconazole was linear in children following doses of
      3 and 4 mg/kg every 12 h. Body weight was more influential than age in accounting
      for the observed variability in voriconazole pharmacokinetics. Elimination
      capacity correlated with the CYP2C19 genotype. Exposures were similar at 4 mg/kg
      every 12 h in children (median area under the concentration-time curve (AUC),
      14,227 ng. h/ml) and 3 mg/kg in adults (median AUC, 13,855 ng. h/ml). Visual
      disturbances occurred in 5 (12.8%) of the 39 patients and were the only drug
      related adverse events that occurred more than once. No withdrawals from the
      study were related to voriconazole. We conclude that pediatric patients have a
      higher capacity for elimination of voriconazole per kilogram of body weight than
      do adult healthy volunteers and that dosages of 4 mg/kg may be required in
      children to achieve exposures consistent with those in adults following dosages
      of 3 mg/kg.

PMID- 15155218
TI  - Effects of growth phase and extracellular slime on photodynamic inactivation of
      gram-positive pathogenic bacteria.
AB  - The emergence of antibiotic resistance among pathogenic bacteria has led to
      efforts to find alternative antimicrobial therapeutics to which bacteria will not
      be easily able to develop resistance. One of these may be the combination of
      nontoxic dyes (photosensitizers [PS]) and visible light, known as photodynamic
      therapy, and we have reported its use to treat localized infections in animal
      models. While it is known that gram-positive species are generally susceptible to
      photodynamic inactivation (PDI), the factors that govern variation in degrees of
      killing are unknown. We used isogenic pairs of wild-type and transposon mutants
      deficient in capsular polysaccharide and slime production generated from
      Staphylococcus epidermidis and Staphylococcus aureus to examine the effects of
      extracellular slime on susceptibility to PDI mediated by two cationic PS (a
      polylysine-chlorin(e6) conjugate, pL-c(e6), and methylene blue [MB]) and an
      anionic molecule, free c(e6), and subsequent exposure to 665-nm light at 0 to 40
      J/cm(2). Free c(e6) gave more killing of mutant strains than wild type, despite
      the latter taking up more PS. Log-phase cultures were killed more than stationary
      phase cultures, and this correlated with increased uptake. The cationic pL-c(e6)
      and MB gave similar uptakes and killing despite a 50-fold difference in
      incubation concentration. Differences in susceptibility between strains and
      between growth phases observed with free c(e6) largely disappeared with the
      cationic compounds despite significant differences in uptake. These data suggest
      that slime production and stationary phase can be obstacles against PDI for gram
      positive bacteria but that these obstacles can be overcome by using cationic PS.

PMID- 15155219
TI  - Effects of efflux transporter genes on susceptibility of Escherichia coli to
      tigecycline (GAR-936).
AB  - The activity of tigecycline, 9-(t-butylglycylamido)-minocycline, against
      Escherichia coli KAM3 (acrB) strains harboring plasmids encoding various
      tetracycline-specific efflux transporter genes, tet(B), tet(C), and tet(K), and
      multidrug transporter genes, acrAB, acrEF, and bcr, was examined. Tigecycline
      showed potent activity against all three Tet-expressing, tetracycline-resistant
      strains, with the MICs for the strains being equal to that for the host strain.
      In the Tet(B)-containing vesicle study, tigecycline did not significantly inhibit
      tetracycline efflux-coupled proton translocation and at 10 microM did not cause
      proton translocation. This suggests that tigecycline is not recognized by the Tet
      efflux transporter at a low concentration; therefore, it exhibits significant
      antibacterial activity. These properties can explain its potent activity against
      bacteria with a Tet efflux resistance determinant. Tigecycline induced the Tet(B)
      protein approximately four times more efficiently than tetracycline, as
      determined by Western blotting, indicating that it is at least recognized by a
      TetR repressor. The MICs for multidrug efflux proteins AcrAB and AcrEF were
      increased fourfold. Tigecycline inhibited active ethidium bromide efflux from
      intact E. coli cells overproducing AcrAB. Therefore, tigecycline is a possible
      substrate of AcrAB and its close homolog, AcrEF, which are resistance-modulation
      division-type multicomponent efflux transporters.

PMID- 15155220
TI  - Pyruvate decarboxylase, the target for omeprazole in metronidazole-resistant and
      iron-restricted Tritrichomonas foetus.
AB  - The substituted benzimidazole omeprazole, used for the treatment of human peptic
      ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen
      Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is
      inhibited by 50%, 22 microg/ml [63 microM]). The antitrichomonad activity appears
      to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key
      enzyme responsible for ethanol production and which is strongly upregulated in
      metronidazole-resistant trichomonads. PDC was purified to homogeneity from the
      cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa
      subunits is inhibited by omeprazole (50% inhibitory concentration, 16 microg/ml).
      Metronidazole-susceptible T. foetus, which expresses very little PDC, is only
      slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells
      grown under iron-limited conditions. Similarly to metronidazole-resistant cells,
      T. foetus cells grown under iron-limited conditions have nonfunctional
      hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol
      fermentation.

PMID- 15155221
TI  - Structure and association of human lactoferrin peptides with Escherichia coli
      lipopolysaccharide.
AB  - An 11-amino-acid amphipathic synthetic peptide homologous to a helical region on
      helix 1 of human lactoferrin HLP-2 exhibited bactericidal activity against
      Escherichia coli serotype O111, whereas an analogue synthesized with Pro
      substituted for Met, HLP-6, had greatly reduced antimicrobial activity. The
      bactericidal activity of HLP-2 was 10-fold greater than that of HLP-6 in both
      buffer and growth medium by time-kill assays. These assays also showed a
      pronounced lag phase that was both concentration and time dependent and that was
      far greater for HLP-2 than for HLP-6. Both peptides, however, were shown to be
      equally efficient in destabilizing the outer membrane when the hydrophobic probe
      1-N-phenylnaphthylamine was used and to have the same lipopolysaccharide (LPS)
      binding affinity, as shown by polymyxin B displacement. Circular dichroism (CD)
      spectroscopy was used to study the structure and the organization of the peptides
      in solution and upon interaction with E. coli LPS. In the presence of LPS, HLP-2
      and HLP-6 were found to bind and adopt a beta-strand conformation rather than an
      alpha-helix, as shown by nonimmobilized ligand interaction assay-CD spectroscopy.
      Furthermore, this assay was used to show that there is a time-dependent
      association of peptide that results in an ordered formation of peptide
      aggregates. The rate of interpeptide association was far greater in HLP-2 LPS
      than in HLP-6 LPS, which was consistent with the lag phase observed on the
      killing curves. These results allow us to propose a mechanism by which HLP-2
      folds and self-assembles at the outer membrane surface before exerting its
      activity.

PMID- 15155222
TI  - Phosphorothioate di- and trinucleotides as a novel class of anti-hepatitis B
      virus agents.
AB  - Several nucleoside analogs are under clinical development for use against
      hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir
      dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However,
      long-term treatment can induce viral resistance, and following the cessation of
      therapy, viral rebound is frequently observed. There continues to be a need for
      new antiviral agents with novel mechanisms of action. A library of more than 600
      di- and trinucleotide compounds synthesized by parallel synthesis using a
      combinatorial strategy was screened for potential inhibitors of HBV replication
      using the chronically HBV-producing cell line 2.2.15. Through an iterative
      process of synthesis, lead optimization, and screening, three analogs were
      identified as potent inhibitors of HBV replication: dinucleotides ORI-7246 (drug
      concentration at which a 10-fold reduction of HBV DNA was observed [EC(90)], 1.4
      microM) and ORI-9020 (EC(90), 1.2 microM) and trinucleotide ORI-7170 (EC(90), 7.2
      microM). These analogs inhibited the replication of both strands of HBV DNA. No
      suppression of HBV protein synthesis or intracellular core particle formation by
      these analogs was observed. No inhibition of HBV DNA strand elongation by the
      analogs or their 5'-triphosphate versions was apparent in in vitro polymerase
      assays. Although the exact mechanism of action is not yet identified, present
      data are consistent with an inhibition of the HBV reverse transcriptase-directed
      priming step prior to elongation of the first viral DNA strand. In transient
      transfection assays, these analogs inhibited the replication of 3TC-resistant
      HBV. Synergistic interactions in combination treatments between the analogs and
      either 3TC or ADV were observed. These compounds represent a novel class of anti
      HBV molecules and warrant further investigation as potential therapeutic agents.

PMID- 15155223
TI  - Short- and long-term effects of pneumococcal conjugate vaccination of children on
      penicillin resistance.
AB  - Recent observations have shown that wide-scale vaccination with pneumococcal
      conjugate vaccines was associated with a reduction in invasive disease,
      supporting the expectation that vaccination could help reduce carriage of
      Streptococcus pneumoniae and control the spread of resistant strains. However, it
      is too early to assess whether these effects can be sustained in the long term.
      Here, we used mathematical modeling to investigate time changes in pneumococcal
      colonization and resistance induced by conjugate vaccination in an environment
      where antibiotic exposure is high and resistance is widespread. According to
      model predictions, vaccination induced a decrease in carriage of vaccine-type
      pneumococci to very low levels, typically in 10 to 15 years under
      epidemiologically realistic conditions. Almost simultaneously, non-vaccine-type
      pneumococci spread in the community. Consequently, while there was a short-term
      decrease in the overall carriage rate, it was followed after a few years by a
      renewed, although limited, increase. Vaccination with a heptavalent vaccine did
      not affect the extent to which antibiotic resistance was selected: in all cases,
      the distribution of resistance levels peaked at high levels (MIC > 2 microg/ml)
      after 20 years. With a vaccine optimally designed to include all serotypes
      currently exhibiting decreased susceptibility to penicillin G, the selection of
      resistance was slowed down, although not prevented. These results suggest that
      because of serotype replacement, the effects of vaccination observed today may
      not be sustained in the long term. As a consequence, vaccination alone may not be
      successful in controlling selection for resistance in S. pneumoniae.

PMID- 15155224
TI  - Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino
      acid in dihydropteroate synthase at the putative sulfadoxine-binding site.
AB  - Sulfadoxine is predominantly used in combination with pyrimethamine, commonly
      known as Fansidar, for the treatment of Plasmodium falciparum. This combination
      is usually less effective against Plasmodium vivax, probably due to the innate
      refractoriness of parasites to the sulfadoxine component. To investigate this
      mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the
      P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three
      dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as
      well as P. falciparum were created. The docking of sulfadoxine to the two DHPS
      models allowed us to compare contact residues in the putative sulfadoxine-binding
      site in both species. The predicted sulfadoxine-binding sites between the species
      differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum.
      V585 in P. vivax is predicted by energy minimization to cause a reduction in
      binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing
      dhps genes from a limited set of geographically different P. vivax isolates
      revealed that V585 was present in all of the samples, suggesting that V585 may be
      responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino
      acid mutations were observed in some P. vivax isolates in positions known to
      cause resistance in P. falciparum, suggesting that, as in P. falciparum, these
      mutations are responsible for acquired increases in resistance of P. vivax to
      sulfadoxine.

PMID- 15155225
TI  - Clade-specific flucytosine resistance is due to a single nucleotide change in the
      FUR1 gene of Candida albicans.
AB  - Population studies have indicated that natural resistance to flucytosine (5FC) in
      Candida albicans is limited to one of the five major clades, clade I. In
      addition, while 73% of clade I isolates are less susceptible to 5FC (MIC >/= 0.5
      microg/ml), only 2% of non-clade I isolates are less susceptible. In order to
      determine the genetic basis for this clade-specific resistance, we sequenced two
      genes involved in the metabolism of 5FC that had previously been linked to
      resistance (cytosine deaminase and uracil phosphoribosyltransferase), in 48
      isolates representative of all clades. Our results demonstrate that a single
      nucleotide change from cytosine to thymine at position 301 in the uracil
      phosphoribosyltransferase gene (FUR1) of C. albicans is responsible for 5FC
      resistance. The mutant allele was found only in group I isolates. The 5FC MICs
      for strains without copies of the mutant allele were almost exclusively </=0.25
      microg/ml, those for strains with one copy of the mutant allele were >/=0.5
      microg/ml, and those for strains with two copies of the mutant allele were >/=16
      microg/ml. Thus, the two alleles were codominant. The presence of this allele is
      responsible for clade I-specific resistance to 5FC within the C. albicans
      population and thus by inference is likely to be the major underlying 5FC
      resistance mechanism in C. albicans. This represents the first description of the
      genetic mutation responsible for 5FC resistance.

PMID- 15155226
TI  - Penetration of meropenem into pneumonic human lung tissue as measured by in vivo
      microdialysis.
AB  - Until recently, information on antibiotic pharmacokinetic properties in infected
      human lung tissue was limited. We therefore studied a microdialysis-based
      approach for measurement of the penetration of meropenem into the extracellular
      space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem
      was determined for seven patients with pneumonia and metapneumonic pleural
      empyema treated by decortication. Intraoperatively, two microdialysis probes were
      inserted into pneumonic lung tissue and one was inserted into healthy skeletal
      muscle for reference values. Serum and microdialysis samples were collected at 20
      min intervals for at least 8 h following a single intravenous dose of 1 g of
      meropenem. The maximum free interstitial concentration (mean and standard
      deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and
      that in serum was 47.3 +/- 21.0 mg/liter. The areas under the curve for infected
      lung tissue (36.2 +/- 17.9 mg. h/liter) and serum (95.4 +/- 46.6 mg. h/liter)
      revealed a significant difference. This technique enabled quasi-continuous tissue
      pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue
      of patients with pneumonia. The present data corroborate the use of meropenem in
      the treatment of lung infections caused by extracellular bacteria, demonstrating
      the excellent distribution profile for meropenem in the interstitial space of
      human pneumonic lung tissue.

PMID- 15155227
TI  - Mechanism of action at the molecular level of the antiviral drug 3(2H)-isoflavene
      against type 2 poliovirus.
AB  - The mechanism of action of the antiviral compound 3(2H)-isoflavene against Sabin
      type 2 poliovirus has been studied, and interference with virus uncoating was
      demonstrated. Isolation and sequencing of drug-resistant variants revealed single
      amino acid substitutions (I194M or D131V) in the VP1 capsid protein. While M194
      is located in a hydrophobic pocket and should partially fill the space occupied
      by the isoflavene ring, V131 is exposed on the VP1 surface, forming a contact
      with VP4. The D131V mutation most likely induces local conformational changes in
      VP1 and/or VP4 that affect viral flexibility. Two dependent variants, N53S of VP1
      and K58E of VP4, both located on the inner surface of the capsid, near the
      threefold axis of symmetry, were also selected. Both mutations affected viral
      stability, allowing the transition to 135S particles in the absence of drug,
      without the involvement of the viral receptor.

PMID- 15155228
TI  - Complete sequences of six penicillin-binding protein genes from 40 Streptococcus
      pneumoniae clinical isolates collected in Japan.
AB  - All six penicillin-binding protein (PBP) genes, namely, pbp1a, pbp1b, pbp2a,
      pbp2b, pbp2x, and pbp3, of 40 Streptococcus pneumoniae clinical isolates,
      including penicillin-resistant S. pneumoniae isolates collected in Japan, were
      completely sequenced. The MICs of penicillin for these strains varied between
      0.015 and 8 microg/ml. In PBP 2X, the Thr550Ala mutation close to the KSG motif
      was observed in only 1 of 40 strains, whereas the Met339Phe mutation in the STMK
      motif was observed in six strains. These six strains were highly resistant (MICs
      >/= 2 microg/ml) to cefotaxime. The MICs of cefotaxime for 27 strains bearing the
      Thr338Ala mutation tended to increase, but the His394Leu mutation next to the SSN
      motif did not exist in these strains. In PBP 2B, the Thr451Ala/Phe/Ser and
      Glu481Gly mutations close to the SSN motif were observed in 24 strains, which
      showed penicillin resistance and intermediate resistance, and the Thr624Gly
      mutation close to the KTG motif was observed in 2 strains for which the imipenem
      MIC (0.5 microg/ml) was the highest imipenem MIC detected. In PBP 1A, the
      Thr371Ser/Ala mutation in the STMK motif was observed in all 13 strains for which
      the penicillin MICs were >/=1 microg/ml. In PBP 2A, the Thr411Ala mutation in the
      STIK motif was observed in one strain for which with the cefotaxime MIC (8
      microg/ml) was the highest cefotaxime MIC detected. On the other hand, in PBPs 1B
      and 3, no mutations associated with resistance were observed. The results
      obtained here support the concept that alterations in PBPs 2B, 2X, and 1A are
      mainly involved in S. pneumoniae resistance to beta-lactam antibiotics. Our
      findings also suggest that the Thr411Ala mutation in PBP 2A may be associated
      with beta-lactam resistance.

PMID- 15155229
TI  - Effect of erythromycin on chronic respiratory infection caused by Pseudomonas
      aeruginosa with biofilm formation in an experimental murine model.
AB  - Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection
      commonly associated with persistent late-stage Pseudomonas aeruginosa infection.
      However, low-dose long-term therapy with certain macrolides is effective in most
      patients with DPB. The present study was designed to examine the effects of long
      term erythromycin (ERY) therapy by using our established murine model of chronic
      respiratory P. aeruginosa infection. ERY or saline was administered from day 80
      after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20,
      40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and
      electron microscopy of the intubated tube were performed. In the murine model,
      treatment with ERY for 80 days significantly reduced the number of viable P.
      aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P.
      aeruginosa on the inner wall of the inoculation tube placed into the murine
      bronchus became significantly thinner after 80 days of ERY treatment. We conclude
      that the clinical efficacy of macrolides in DPB may be due at least in part to
      the reduction in P. aeruginosa biofilm formation.

PMID- 15155231
TI  - Efficacy of cidofovir in a murine model of disseminated progressive vaccinia.
AB  - An animal model that mimics progressive disseminated vaccinia was elaborated. To
      this end nude (athymic) mice were inoculated intracutaneously with vaccinia virus
      in the lumbosacral area. Viral replication (DNA) in the skin was detected as
      early as day 2 postinfection (p.i.). Mice developed typical vaccinia lesions at
      the site of inoculation by day 4 to 6 p.i. By about 2 weeks p.i., the infection
      had spread all over the body, a situation reminiscent of disseminated vaccinia in
      humans. The infection resulted in viremia and spread of the virus to visceral
      organs, as well as to the brain. Topical treatment with cidofovir, initiated at
      the day of infection or at day 1 p.i., completely protected against virus-induced
      cutaneous lesions and against associated mortality. When treatment was initiated
      at a later time (day 2 to 5 p.i.), a partial but marked protective effect was
      noted, which can be explained by the fact that by that time, the virus had spread
      from the skin to the visceral organs. Next, infected animals were left untreated
      until the time ( approximately 2 weeks p.i.) at which disseminated vaccinia had
      developed. When systemic treatment with cidofovir was initiated at that time, it
      caused lesions to heal and regress. In most of these animals, lesions had
      completely (or almost completely) disappeared by day 10 to 15 after the start of
      therapy. The observation that cidofovir is able to cause healing of disseminated
      vaccinia lesions in animals should have implications for the therapy of
      complications of vaccination against smallpox.

PMID- 15155230
TI  - Mutations conferring resistance to a potent hepatitis C virus serine protease
      inhibitor in vitro.
AB  - BILN 2061 is a novel, specific hepatitis C virus (HCV) NS3 serine protease
      inhibitor discovered by Boehringer Ingelheim that has shown potent activity
      against HCV replicons in tissue culture and is currently under clinical
      investigation for the treatment of HCV infection. The poor fidelity of the HCV
      RNA-dependent RNA polymerase will likely lead to the development of drug
      resistant viruses in treated patients. The development of resistance to BILN 2061
      was studied by the in vitro passage of HCV genotype 1b replicon cells in the
      presence of a fixed concentration of the drug. Three weeks posttreatment, four
      colonies were expanded for genotypic and phenotypic characterization. The 50%
      inhibitory concentrations of BILN 2061 for these colonies were 72- to 1,228-fold
      higher than that for the wild-type replicon. Sequencing of the individual
      colonies identified several mutations in the NS3 serine protease gene. Molecular
      clones containing the single amino acid substitution A156T, R155Q, or D168V
      resulted in 357-fold, 24-fold, and 144-fold reductions in susceptibility to BILN
      2061, respectively, compared to the level of susceptibility shown by the wild
      type replicon. Modeling studies indicate that all three of these residues are
      located in close proximity to the inhibitor binding site. These findings, in
      addition to the three-dimensional structure analysis of the NS3/NS4A serine
      protease inhibitor complex, provide a strategic guide for the development of next
      generation inhibitors of HCV NS3/NS4A serine protease.

PMID- 15155232
TI  - Regulatory regions of smeDEF in Stenotrophomonas maltophilia strains expressing
      different amounts of the multidrug efflux pump SmeDEF.
AB  - The smeT-smeDEF region and the smeT gene, which encodes the smeDEF repressor, are
      highly polymorphic. Few changes in smeT might be associated with smeDEF
      overexpression. The results obtained with cellular extracts suggest that mutant
      SmeT proteins cannot bind to the operator and that other transcription factors
      besides SmeT are involved in the regulation of smeDEF expression.

PMID- 15155233
TI  - Nosocomial outbreak of extended-spectrum beta-lactamase SHV-5-producing isolates
      of Pseudomonas aeruginosa in Athens, Greece.
AB  - Seven nonrepetitive Pseudomonas aeruginosa isolates producing the clavulanic acid
      inhibited extended-spectrum beta-lactamase SHV-5 were isolated in the same
      hospital in Athens, Greece, from 1998 to 2002. All isolates except one were
      clonally related, and the bla(SHV-5) gene was chromosomally located. This study
      underlined that this gene, which is widespread in Enterobacteriaceae in Greece,
      may disseminate also in P. aeruginosa.

PMID- 15155234
TI  - In vitro activity of OPT-80 against Clostridium difficile.
AB  - Clostridium difficile remains the major cause of nosocomial diarrhea. Reports on
      impaired susceptibility of C. difficile to metronidazole and vancomycin and
      frequent relapses of patients after therapy necessitate the search for new
      substances. With this study, the activity of OPT-80, a new macrocycle, against
      207 C. difficile strains and against other obligately anaerobic bacteria was
      tested. OPT-80 showed high in vitro activity against all C. difficile strains
      tested.

PMID- 15155235
TI  - Noninvasive optical imaging method to evaluate postantibiotic effects on biofilm
      infection in vivo.
AB  - Eradication of Staphylococcus aureus biofilms after rifampin treatment was tested
      in a mouse model of device-related infection by using biophotonic imaging.
      Following treatment, the bioluminescent signals decreased to undetectable levels,
      irrespective of the age of the biofilm. After the final treatment, the signals
      rebounded in a time-dependent manner and reached those for the untreated mice.
      Readministration of rifampin was unsuccessful in eradicating reestablished
      infections, with the rifampin MICs for such bacteria being increased and with the
      bacteria having point mutations in the rpoB gene.

PMID- 15155236
TI  - Posaconazole therapy of disseminated phaeohyphomycosis in a murine model.
AB  - Immunocompetent (nu/+) and athymic (nu/nu) BALB/c mice were infected
      intravenously with Wangiella dermatitidis and treated with posaconazole.
      Posaconazole reduced the counts in tissues and prolonged survival. Of particular
      interest, posaconazole reduced the counts of this neurotropic pathogen in the
      brain.

PMID- 15155237
TI  - Salmonella gene rma (ramA) and multiple-drug-resistant Salmonella enterica
      serovar typhimurium.
AB  - MarA and its homologue, RamA, have been implicated in multidrug resistance (MDR).
      RamA overexpression in Salmonella enterica serovar Typhimurium and Escherichia
      coli conferred MDR independently of marA. Inactivation of ramA did not affect the
      antibiotic susceptibilities of wild-type S. enterica serovar Typhimurium or 15
      unrelated clinical MDR isolates. Thus, ramA overexpression is not a common MDR
      mechanism in Salmonella.

PMID- 15155238
TI  - Fitness cost of SCCmec and methicillin resistance levels in Staphylococcus
      aureus.
AB  - Transformation of a type I SCCmec element into Staphylococcus aureus yielded
      highly oxacillin-resistant transformants with a reduced growth rate. Faster
      growing variants could again be selected at the cost of reduced resistance
      levels, demonstrating an inverse correlation between oxacillin resistance levels
      and growth rate.

PMID- 15155239
TI  - Genetic basis of erythromycin resistance in oral bacteria.
AB  - We determined the prevalence of erythromycin-resistant bacteria in the oral
      cavity and identified mef and erm(B) as the most common resistance determinants.
      In addition, we demonstrate the genetic linkage, on various Tn1545-like
      conjugative transposons, between erythromycin and tetracycline resistance in a
      number of isolates.

PMID- 15155240
TI  - In vitro effects of albendazole sulfoxide and praziquantel against Taenia solium
      and Taenia crassiceps cysts.
AB  - We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole
      sulfoxide (ABZSO) required for their activities against Taenia cysts in vitro as
      well as the 50 and 99% effective concentrations. The results showed that although
      the effects of both drugs are time and concentration dependent, ABZSO acts much
      slower and is less potent than PZQ.

PMID- 15155241
TI  - Enhanced production of farnesol by Candida albicans treated with four azoles.
AB  - The dimorphic fungus Candida albicans excretes farnesol, which is produced
      enzymatically from the sterol biosynthetic intermediate farnesyl pyrophosphate.
      Inhibition of C. albicans by four azole antifungals, fluconazole, ketoconazole,
      miconazole, and clotrimazole, caused elevated farnesol production (10- to 45
      fold). Furthermore, farnesol production occurs in both laboratory strains and
      clinical isolates (J. M. Hornby et al., Appl. Environ. Microbiol. 67:2982-2992,
      2001) of C. albicans.

PMID- 15155242
TI  - High-level resistance to ceftazidime conferred by a novel enzyme, CTX-M-32,
      derived from CTX-M-1 through a single Asp240-Gly substitution.
AB  - A clinical strain of Escherichia coli isolated from pleural liquid with high
      levels of resistance to cefotaxime, ceftazidime, and aztreonam harbors a novel
      CTX-M gene (bla(CTX-M-32)) whose amino acid sequence differs from that of CTX-M-1
      by a single Asp240-Gly substitution. Moreover, by site-directed mutagenesis we
      demonstrated that this replacement is a key event in ceftazidime hydrolysis

PMID- 15155243
TI  - Immunopharmacology of CpG oligodeoxynucleotides and ribavirin.
AB  - To investigate their potential mechanisms of action, the nucleoside analogue
      ribavirin and a TLR9 agonist were compared. The CpG oligodeoxynucleotides (ODN)
      demonstrated strong TLR9-related Th1-type effects, and ribavirin appeared only to
      mediate signaling in TLR-transfected cells. CpG ODN represent a promising new
      type of therapeutic drug for hepatitis C or other infectious diseases.

PMID- 15155244
TI  - Anti-hepatitis B virus activity of ORI-9020, a novel phosphorothioate
      dinucleotide, in a transgenic mouse model.
AB  - ORI-9020, a novel dinucleotide, evaluated in transgenic mice expressing hepatitis
      B virus (HBV), significantly reduced liver HBV DNA (P </= 0.001). Levels of HBeAg
      and HBsAg in serum and of HBcAg in liver were not affected by treatment. A
      minimal effective dosage was determined to be between 1.6 and 0.5 mg/kg of body
      weight/day, which was similar to that observed for adefovir dipivoxil.

PMID- 15155245
TI  - Molecular characterization of a carbapenem-hydrolyzing class A beta-lactamase,
      SFC-1, from Serratia fonticola UTAD54.
AB  - An environmental isolate of Serratia fonticola resistant to carbapenems contains
      a gene encoding a class A beta-lactamase with carbapenemase activity. The enzyme
      was designated SFC-1. The bla(SFC-I) gene is contained in the chromosome of S.
      fonticola UTAD54 and is absent from other S. fonticola strains.

PMID- 15155246
TI  - Potential new anti-human immunodeficiency virus type 1 compounds depress virus
      replication in cultured human macrophages.
AB  - We report that the amiloride analogues 5-(N,N-hexamethylene)amiloride and 5-(N,N
      dimethyl)amiloride inhibit, at micromolar concentrations, the replication of
      human immunodeficiency virus type 1 (HIV-1) in cultured human blood monocyte
      derived macrophages. These compounds also inhibit the in vitro activities of the
      HIV-1 Vpu protein and might represent lead compounds for a new class of anti-HIV
      1 drugs.

PMID- 15155247
TI  - ELVIRA HSV, a yield reduction assay for rapid herpes simplex virus susceptibility
      testing.
AB  - A colorimetric yield reduction assay, ELVIRA (enzyme-linked virus inhibitor
      reporter assay) HSV, was developed to determine the antiviral drug
      susceptibilities of herpes simplex virus (HSV). It uses an HSV-inducible reporter
      cell line. This simple and rapid assay has an objective readout, low inoculum
      size, and good reproducibility. The results correlate well with those of the
      plaque reduction assay.

PMID- 15155248
TI  - IMP-1 and a novel metallo-beta-lactamase, VIM-6, in fluorescent pseudomonads
      isolated in Singapore.
AB  - Four carbapenem-resistant Pseudomonas spp. were isolated from patients in
      Singapore. One Pseudomonas putida isolate contained a bla(IMP-1) identical to
      that first described in Japan. The sequence of a variant bla(IMP-1) in
      Pseudomonas fluorescens contained four silent mutations compared with the
      original sequence. The remaining P. putida isolates contained bla(VIM-6), a novel
      VIM gene variant.

PMID- 15155249
TI  - Lack of effect of recombinant human growth hormone on the in vitro activities of
      antiretroviral drugs against human immunodeficiency virus type 1.
AB  - We studied the effects of recombinant human growth hormone (r-hGH) on human
      immunodeficiency virus type 1 replication by growing both wild-type and drug
      resistant variants of virus in the presence of various concentrations of eight
      different antiretroviral drugs. r-hGH had no significant effect on either viral
      replication or the 50% inhibitory concentrations of these compounds.

PMID- 15155250
TI  - Successful use of voriconazole for treatment of Coccidioides meningitis.

PMID- 15155251
TI  - Aeromonas hydrophila with plasmid-borne class A extended-spectrum beta-lactamase
      TEM-24 and three chromosomal class B, C, and D beta-lactamases, isolated from a
      patient with necrotizing fasciitis.

PMID- 15155252
TI  - Emergence of the extended-spectrum beta-lactamase GES-1 in a Pseudomonas
      aeruginosa strain from Brazil: report from the SENTRY antimicrobial surveillance
      program.

PMID- 15155254
TI  - Measuring hemodynamic changes during mammalian development.
AB  - The pathogenesis of many congenital cardiovascular diseases involves abnormal
      flow within the embryonic vasculature that results either from malformations of
      the heart or defects in the vasculature itself. Extensive genetic and genomic
      analysis in mice has led to the identification of an array of mutations that
      result in cardiovascular defects during embryogenesis. Many of these mutations
      cause secondary effects within the vasculature that are thought to arise because
      of altered fluid dynamics. Presumably, cardiac defects disturb or reduce flow and
      thereby lead to the disruption of the mechanical signals necessary for proper
      vascular development. Unfortunately, a precise understanding of how flow
      disruptions lead to secondary vasculature defects has been hampered by the
      inadequacy of existing analytical tools. Here, we used a fast line-scanning
      technique for the quantitative analysis of hemodynamics during early
      organogenesis in mouse embryos, and we present a model system for studying
      cellular responses during the formation and remodeling of the mammalian
      cardiovascular system. Flow velocity profiles can be measured as soon as a heart
      begins to beat even in newly formed vessels. These studies establish a link
      between the pattern of blood flow within the vasculature and the stage of heart
      development and also enable analysis of the influence of mechanical forces during
      development.

PMID- 15155255
TI  - Preload-adjusted right ventricular maximal power: concept and validation.
AB  - Right ventricular (RV) maximal power (PWR(mx)) is dependent on preload. The
      objective of this study was to test our hypothesis that the PWR(mx) versus end
      diastolic volume (EDV) relationship, analogous to the load-independent stroke
      work (SW) versus EDV relationship (preload-recruitable SW, PRSW), is linear, with
      the PWR x-axis intercept (V(0PWR)) corresponding to the PRSW intercept (V(0SW)).
      If our hypothesis is correct, the preload sensitivity of PWR(mx) could be
      eliminated by adjusting for EDV and V(0PWR). Ten dogs were instrumented with a
      pulmonary flow probe, micromanometers, and RV conductance catheter. Data were
      obtained during bicaval occlusions under various conditions and fitted to PWR(mx)
      = a.(EDV - V(0PWR))(beta), where a is the slope of the relationship. The PWR(mx)
      versus EDV relationship did not deviate from linearity (beta = 1.09, P = not
      significant vs. 1), and V(0PWR) correlated with V(0SW) (r = 0.93, P <0.0001).
      V(0PRW) was related to steady-state EDV and left ventricular end-diastolic
      pressure, allowing for estimation of V(0PWR) (V(0Est)) and single-beat PWR(mx)
      preload adjustment. Dividing PWR(mx) by the difference of EDV and V(0PWR)
      (PAMP(V0PWR)) eliminated preload dependency down to 50% of the baseline EDV.
      PWR(mx) adjustment using V(0Est) (PAMP(V0Est)) showed similar preload
      independency. Enhancing contractility increased PAMP(V0PWR) and PAMP(V0Est) from
      176 +/- 52 to 394 +/- 205 W/ml x 10(4) and 145 +/- 51 to 404 +/- 261 W/ml x
      10(4), respectively, accompanied by an increase of PRSW from 13.0 +/- 4.5 to 29.7
      +/- 16.4 mmHg (all P <0.01). PAMP(V0PWR) and PAMP(V0Est) correlated with PRSW (r
      = 0.85; r = 0.77; both P <0.001). Numerical modeling confirmed the accuracy of
      our experimental data. Thus preload adjustment of PWR(mx) should consider a
      linear PWR(mx) versus EDV relationship with distinct V(0PWR). PAMP(V0PWR) is a
      preload-independent estimate of RV contractility that may eventually be
      determined noninvasively.

PMID- 15155256
TI  - Regulation of free radical outflow from an isolated muscle bed in exercising
      humans.
AB  - Incremental knee extensor (KE) exercise performed at 25, 70, and 100% of single
      leg maximal work rate (WR(MAX)) was combined with ex vivo electron paramagnetic
      resonance (EPR) spectroscopic detection of alpha-phenyl-tert-butylnitrone (PBN)
      adducts, lipid hydroperoxides (LH), and associated parameters in five males.
      Blood samples were taken from the femoral arterial and venous circulation that,
      when combined with measured changes in femoral venous blood flow, permitted a
      direct examination of oxidant exchange across a functionally isolated contracting
      muscle bed. KE exercise progressively increased the net outflow of LH and PBN
      adducts (100% > 70% > 25% WR(MAX), P < 0.05) consistent with the generation of
      secondary, lipid-derived oxygen (O(2))-centered alkoxyl and carbon-centered alkyl
      radicals. Radical outflow appeared to be more intimately associated with
      predicted decreases in intracellular Po(2) (iPo(2)) as opposed to measured
      increases in leg O(2) uptake, with greater outflow recorded between 25 and 70%
      WR(MAX) (P < 0.05 vs. 70-100% WR(MAX)). This bias was confirmed when radical
      venoarterial concentration differences were expressed relative to changes in the
      convective components of O(2) extraction and flow (25-70% WR(MAX) P < 0.05 vs. 70
      100% WR(MAX), P > 0.05). Exercise also resulted in a net outflow of other
      potentially related redox-reactive parameters, including hydrogen ions,
      norepinephrine, myoglobin, lactate dehydrogenase, and uric acid, whereas exchange
      of lipid/lipoproteins, ascorbic acid, and selected lipid-soluble anti-oxidants
      was unremarkable. These findings provide direct evidence for an exercise
      intensity-dependent increase in free radical outflow across an active muscle bed
      that was associated with an increase in sarcolemmal membrane permeability. In
      addition to increased mitochondrial electron flux subsequent to an increase in
      O(2) extraction and flow, exercise-induced free radical generation may also be
      regulated by changes in iPo(2), hydrogen ion generation, norepinephrine
      autoxidation, peroxidation of damaged tissue, and xanthine oxidase activation.

PMID- 15155257
TI  - Neuroprotection by a selective estrogen receptor beta agonist in a mouse model of
      global ischemia.
AB  - The present study employs selective estrogen receptor (ER) agonists to determine
      whether 17beta-estradiol-induced neuroprotection in global ischemia is receptor
      mediated and, if so, which subtype of receptor (ERalpha or ERbeta) is
      predominantly responsible. Halothane-anesthetized female C57Bl/6J mice were
      ovariectomized, and osmotic minipumps containing ERbeta agonist
      diarylpropiolnitrile (DPN) (8 mg.kg(-1).day(-1), n = 12) or vehicle (50% DMSO in
      0.9% saline) (n = 9) or ERalpha agonist propyl pyrazole triol (PPT) (2 mg.kg(
      1).day(-1), n = 13) or vehicle (50% DMSO in 0.9% saline) (n = 10) were implanted
      subcutaneously. One week later transient global ischemia was induced by bilateral
      carotid artery occlusion under halothane anesthesia, and the mice were perfusion
      fixed 72 h later. ERbeta agonist DPN significantly reduced ischemic damage by 70%
      in the caudate nucleus and 55% in the CA1 region compared with vehicle controls
      (P < 0.05, Mann-Whitney U-statistic). In contrast, pretreatment with the ERalpha
      agonist PPT had no effect on the extent of neuronal damage compared with
      controls. The data indicate a significant estrogen receptor-mediated
      neuroprotection in a global cerebral ischemia model involving ERbeta.

PMID- 15155258
TI  - Coverslip hypoxia: a novel method for studying cardiac myocyte hypoxia and
      ischemia in vitro.
AB  - In vitro experimental models designed to study the effects of hypoxia and
      ischemia typically employ oxygen-depleted media and/or hypoxic chambers. These
      approaches, however, allow for metabolites to diffuse away into a large volume
      and may not replicate the high local concentrations that occur in ischemic
      myocardium in vivo. We describe herein a novel and simple method for creating
      regional hypoxic and ischemic conditions in neonatal rat cardiac myocyte
      monolayers. This method consists of creating a localized diffusion barrier by
      placing a glass coverslip over a portion of the monolayer. The coverslip
      restricts covered myocytes to a thin film of media while leaving uncovered
      myocytes free to access the surrounding bulk media volume. Myocytes under the
      coverslip undergo marked morphology changes over time as assessed by video
      microscopy. Fluorescence microscopy shows that these changes are accompanied by
      alterations in mitochondrial membrane potential and plasma membrane dynamics and
      eventually result in myocyte death. We also show that the metabolic activity of
      myocytes drives cell necrosis under the coverslip. In addition, the intracellular
      pH of synchronously contracting myocytes under the coverslip drops rapidly, which
      further implicates metabolic activity in regulating cell death under the
      coverslip. In contrast with existing models of hypoxia/ischemia, this technique
      provides a simple and effective way to create hypoxic/ischemic conditions in
      vitro. Moreover, we conclude that myocyte death is hastened by the combination of
      hypoxia, metabolites, and acidosis and is facilitated by a reduction in media
      volume, which may better represent ischemic conditions in vivo.

PMID- 15155259
TI  - Time-varying effective mitral valve area: prediction and validation using cardiac
      MRI and Doppler echocardiography in normal subjects.
AB  - Precise knowledge of the volume and rate of early rapid left ventricular (LV)
      filling elucidates kinematic aspects of diastolic physiology. The Doppler E wave
      velocity-time integral (VTI) is conventionally used as the estimate of early,
      rapid-filling volume; however, this implicitly requires the assumption of a
      constant effective mitral valve area (EMVA). We sought to evaluate whether the
      EMVA is truly constant throughout early, rapid filling in 10 normal subjects
      using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler
      echocardiography, which were synchronized via ECG. LV volume measurements as a
      function of time were obtained via MRI, and transmitral flow values were measured
      via Doppler echocardiography. The synchronized data were used to predict EMVA as
      a function of time during early diastole. Validation involved EMVA determination
      using 1) the short-axis echocardiographic images near the mitral valve leaflet
      tips, 2) the distance between leaflet tips in the echocardiographic parasternal
      long-axis view, and 3) the distance between leaflet tips from the MRI LV outflow
      tract view. Predicted EMVA values varied substantially during early rapid
      filling, and observed EMVA values agreed well with predictions. We conclude that
      the EMVA is not constant, and its variation causes LV volume to increase faster
      than is reflected by the VTI. These results reveal the mechanism of early rapid
      volumetric increase and directly affect the significance and physiological
      interpretation of the VTI of the Doppler E wave. Application to subjects in
      selected pathophysiological subsets is in progress.

PMID- 15155260
TI  - Vascular endothelial growth factor stimulates differential signaling pathways in
      in vivo microcirculation.
AB  - Vascular endothelial growth factor (VEGF) induces mild vasodilation and strong
      increases in microvascular permeability. Using intravital microscopy and digital
      integrated optical intensity image analysis, we tested, in the hamster cheek
      pouch microcirculation, the hypothesis that differential signaling pathways in
      arterioles and venules represent an in vivo regulatory mechanism in the control
      of vascular diameter and permeability. The experimental design involved blocking
      specific signaling molecules and simultaneously assessing VEGF-induced changes in
      arteriolar diameter and microvascular transport of FITC-Dextran 150. Inhibition
      of Akt [indirectly via phosphatidylinositol 3-kinase with LY-294002 or
      wortmannin] or PKC (with bisindolylmaleimide) reduced VEGF-induced
      hyperpermeability. However, phosphatidylinositol 3-kinase/Akt inhibition enhanced
      the early phase and attenuated the late phase of VEGF-induced vasodilation,
      whereas blocking PKC had no effect. Inhibition of extracellular signal-regulated
      kinase (ERK)-1/2 (with PD-98059 or AG-126) also reduced VEGF-induced
      hyperpermeability but did not block VEGF-induced vasodilation. Blockade of
      endothelial nitric oxide synthase (with N(omega)-monomethyl-l-arginine) inhibited
      VEGF-induced changes in both permeability and diameter. Furthermore,
      immunofluorescence studies with human umbilical vein endothelial cells revealed
      that bisindolylmaleimide, PD-98059, and l-NMMA attenuate VEGF-induced
      reorganization of vascular endothelial cadherin. Our data demonstrate that 1)
      endothelial nitric oxide synthase is a common convergence pathway for VEGF
      induced changes in arteriolar diameter and microvascular permeability; 2) PKC and
      ERK-1/2 do not play a major role in VEGF-induced vasodilation in the hamster
      cheek pouch microcirculation; and 3) Akt, PKC, and ERK-1/2 are elements of the
      signaling cascade that regulates VEGF-stimulated microvascular hyperpermeability.
      Our data provide evidence for differential signaling as a regulatory step in VEGF
      stimulated microvascular dynamics.

PMID- 15155261
TI  - Overexpression of human beta2-adrenergic receptors increases gain of excitation
      contraction coupling in mouse ventricular myocytes.
AB  - This study investigated cardiac excitation-contraction coupling at 37 degrees C
      in transgenic mice with cardiac-specific overexpression of human beta2-adrenergic
      receptors (TG4 mice). In field-stimulated myocytes, contraction was significantly
      greater in TG4 compared with wild-type (WT) ventricular myocytes. In contrast,
      when duration of depolarization was controlled with rectangular voltage clamp
      steps, contraction amplitudes initiated by test steps were the same in WT and TG4
      myocytes. When cells were voltage clamped with action potentials simulating TG4
      and WT action potential configurations, contractions were greater with long TG4
      action potentials and smaller with shorter WT action potentials, which suggests
      an important role for action potential configuration. Interestingly, peak
      amplitude of L-type Ca2+ current (I(Ca-L)) initiated by rectangular test steps
      was reduced, although the voltage dependencies of contractions and currents were
      not altered. To explore the basis for the altered relation between contraction
      and I(Ca-L), Ca2+ concentrations were measured in myocytes loaded with fura 2.
      Diastolic concentrations of free Ca2+ and amplitudes of Ca2+ transients were
      similar in voltage-clamped myocytes from WT and TG4 mice. However, sarcoplasmic
      reticulum (SR) Ca2+ content assessed with the rapid application of caffeine was
      elevated in TG4 cells. Increased SR Ca2+ was accompanied by increased frequency
      and amplitudes of spontaneous Ca2+ sparks measured at 37 degrees C with fluo 3.
      These observations suggest that the gain of Ca(2+)-induced Ca2+ release is
      increased in TG4 myocytes. Increased gain counteracts the effects of decreased
      amplitude of I(Ca-L) in voltage-clamped myocytes and likely contributes to
      increased contraction amplitudes in field-stimulated TG4 myocytes.

PMID- 15155262
TI  - Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase
      of sepsis.
AB  - Ghrelin, a newly identified endogenous ligand for growth hormone secretagogue
      receptor 1a (GHSR-1a, i.e., ghrelin receptor), was recently demonstrated to be a
      potent vasoactive peptide. Although sepsis is characterized by an early,
      hyperdynamic phase, it remains unknown whether ghrelin or GHSR-1a plays a role in
      the cardiovascular response to sepsis. To determine this, polymicrobial sepsis
      was induced by cecal ligation and puncture in male adult rats. At 5 h (i.e.,
      early sepsis) or 20 h (i.e., late sepsis) after cecal ligation and puncture,
      blood and tissue samples were collected. Ghrelin levels and ghrelin and GHSR-1a
      mRNA expression were assessed by RIA and RT-PCR, respectively. In addition, GHSR
      1a protein levels in aorta, heart, and small intestine were determined by Western
      blotting. The vascular response to ghrelin was determined by using an isolated
      gut preparation. A primary rat aortic smooth muscle cell culture was used to
      determine the effects of LPS on GHSR-1a expression. The results indicate that
      although ghrelin levels decreased at early and late sepsis, its receptor was
      markedly elevated in early sepsis. Moreover, ghrelin-induced relaxation in
      resistance blood vessels of the isolated small intestine increased significantly
      during early sepsis but was not altered in late sepsis. Furthermore, GHSR-1a
      expression in smooth muscle cells was significantly increased at mRNA and protein
      levels with stimulation by LPS at 10 ng/ml. These results demonstrate that GHSR
      1a expression is upregulated and vascular sensitivity to ghrelin stimulation is
      increased in the hyperdynamic phase of sepsis.

PMID- 15155263
TI  - Na+/Ca2+ exchanger plays a key role in inducing apoptosis after hypoxia in
      cultured guinea pig ventricular myocytes.
AB  - Altered Na(+)/Ca(2+) exchanger (NCX) protein expression or activity is thought to
      contribute to various aspects of cardiac pathology. In guinea pig ventricular
      myocytes, NCX-mediated Ca(2+) entry is almost entirely responsible for Ca(2+)
      overload during hypoxia-reoxygenation. Because Ca(2+) overload is a common
      initiator of apoptosis, the purpose of this study was to test the hypotheses that
      NCX activity is critically involved in initiating apoptosis after hypoxia
      reoxygenation and that hypoxia-reoxygenation-induced apoptosis can be modulated
      by changes in NCX protein expression or activity. An NCX antisense
      oligonucleotide was used to reduce NCX protein expression in cultured adult
      guinea pig ventricular myocytes. Caspase-3 activation and cytochrome c release
      were used as markers of apoptosis. Hypoxia-reoxygenation-induced apoptosis was
      significantly decreased in antisense-treated myocytes compared with untreated
      control or nonsense-treated myocytes. Pretreatment of cultured myocytes for 24 h
      with either endothelin-1 or phenylephrine was found to increase both NCX protein
      expression and evoked NCX activity as well as enhance hypoxia-reoxygenation
      induced apoptosis. Control experiments demonstrated that endothelin-1 and
      phenylephrine did not induce apoptosis on their own nor did they enhance the
      apoptotic response in a model of Ca(2+)-dependent, NCX-independent apoptosis.
      Additional control experiments demonstrated that the NCX antisense
      oligonucleotide did not alter the apoptotic response of myocytes to either
      H(2)O(2) or isoproterenol. Taken together, these data suggest that the NCX has a
      critical and specific role in the initiation of apoptosis after hypoxia
      reoxygenation in guinea pig myocytes and that hypoxia-reoxygenation-induced
      apoptosis is quite sensitive to changes in NCX activity.

PMID- 15155264
TI  - Rat corin gene: molecular cloning and reduced expression in experimental heart
      failure.
AB  - Stored cardiac pro-atrial natriuretic peptide (pro-ANP) is converted to ANP and
      released upon stretch from the atria into the circulation. Corin is a serin
      protease with pro-ANP-converting properties and may be the rate-limiting enzyme
      in ANP release. This study was aimed to clone and sequence corin in the rat and
      to analyze corin mRNA expression in heart failure when ANP release upon stretch
      is blunted. Full-length cDNA of rat corin was obtained from atrial RNA by RT-PCR
      and sequenced. Tissue distribution as well as regulation of corin mRNA expression
      in the atria were determined by RT-PCR and RNase protection assay. Heart failure
      was induced by an infrarenal aortocaval shunt. Stretch was applied to the left
      atrium in a working heart modus, and ANP was measured in the perfusates. The
      sequence of rat corin cDNA was found to be 93.6% homologous to mouse corin cDNA.
      Corin mRNA was expressed almost exclusively in the heart with highest
      concentrations in both atria. The aortocaval shunt led to cardiac hypertrophy and
      heart failure. Stretch-induced ANP release was blunted in shunt animals (control
      1,195 +/- 197 fmol.min(-1).g(-1); shunt: 639 +/- 99 fmol.min(-1).g(-1), P <
      0.05). Corin mRNA expression was decreased in both atria in shunt animals [right
      atrium: control 0.638 +/- 0.004 arbitrary units (AU), shunt 0.566 +/- 0.014 AU, P
      < 0.001; left atrium: control 0.564 +/- 0.009 AU, shunt 0.464 +/- 0.009 AU, P <
      0.001]. Downregulation of atrial corin mRNA expression may be a novel mechanism
      for the blunted ANP release in heart failure.

PMID- 15155265
TI  - Mechanical and energetic effects of chronic chagasic patients' antibodies on rat
      myocardium.
AB  - Chagasic (Ch) and nonchagasic (NCh) IgG fraction (20 microg/ml) effects on
      cardiac performance of adult Wistar rat ventricles were studied with a novel
      approach applying a microcalorimetric technique. Resting heat (Hr) was
      significantly decreased by Ch antibodies (DeltaHrCh = 4.8 +/- 0.9 mW/g). Although
      the Hr decrease can be associated with diminished activity of the Na+/K+ pump,
      the magnitude of the effect (25% of control Hr) indicates that additional
      processes may also be affected. Ch antibodies induced an initial increase in
      developed pressure (P), which was associated with a decreased contractile
      economy. However, after 30 min of Ch antibody perfusion, P reached a
      significantly lower level (DeltaPCh = 3.8 +/- 1.2 mN/mm2) without changes in
      active heat per beat (Ha'). Consequently, Ha'/P ratio increased, indicating that
      the energetic cost per unit of P was higher. In contrast, P and Ha' were both
      significantly and reversibly decreased by NCh antibodies (DeltaPNCh = 4.4 +/- 1.2
      mN/mm2; DeltaHa'NCh = 9.7 +/- 2.2 mJ/g), but Ha'/P remained unaffected. According
      to these data, normal hearts exposed to Ch antibodies present a biphasic
      mechanical response: 1) an initial period of increased contractility (and
      decreased global muscle economy) consistent with antibodies with beta1-adrenergic
      activity, such as those used in the present study, and 2) a decrease in P at 30
      min of Ch antibody perfusion, which suggests that another Ca(2+)-related
      mechanism is compromised. These data contribute to redefine the role of antibody
      mediated responses in the pathophysiology of chronic chagasic cardiomyopathy as
      agents of myocardial failure.

PMID- 15155266
TI  - Effects of anesthetics on systemic hemodynamics in mice.
AB  - The aim of this study was to compare the systemic hemodynamic effects of four
      commonly used anesthetic regimens in mice that were chronically instrumented for
      direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and
      C57BL6 strains) were instrumented with a transit-time flow probe placed around
      the ascending aorta for CO measurement. An arterial catheter was inserted into
      the aorta 4 or 5 days later for blood pressure measurements. After full recovery,
      hemodynamic parameters including stroke volume, heart rate, CO, mean arterial
      pressure (MAP), and total peripheral resistance were measured with animals in the
      conscious state. General anesthesia was then induced in these mice using
      isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The
      doses and routes of administration of these agents were given as required for
      general surgical procedures in these animals. Compared with the values obtained
      for animals in the conscious resting state, MAP and CO decreased during all
      anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24
      +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, 
      37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully
      antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n
      = 8 mice). These results indicate that the anesthetic Iso has fewer systemic
      hemodynamic effects in mice than the nonvolatile anesthetics.

PMID- 15155267
TI  - Na-K-2Cl cotransporter inhibition impairs human lung cellular proliferation.
AB  - The widespread presence of the Na-K-2Cl (NKCC) cotransporter protein suggests
      that chronic administration of inhibitors may result in adverse effects.
      Inhibition of the NKCC cotransporter by loop diuretics is felt to underlie the
      diuretic and the pulmonary smooth muscle relaxant effects of this drug class.
      However, the fundamental regulation of salt and water movement by this
      cotransporter suggests that it may also mediate cell volume changes occurring
      during cell cycle progression. Thus we hypothesized that NKCC cotransporter
      inhibition by loop diuretics would decrease cellular proliferation. Normal human
      bronchial smooth muscle cells (BSMC) showed a significant concentration-dependent
      decrease in cell counts after 7 days of exposure to both bumetanide (n=5-10) and
      furosemide (n=6-16) compared with controls. Proliferation was similarly inhibited
      in normal human lung fibroblasts (n=5-9). To determine whether this was due to
      loss of cells, we performed apoptosis assays on BSMC. Both annexin V-propidium
      iodide staining (n=5-10) and single cell gel electrophoresis assays (n=4) were
      negative for necrosis and apoptosis in BSMC exposed to 10 microM bumetanide.
      Subsequent analysis of the cell cycle by flow cytometry showed that bumetanide
      exposed BSMC were delayed in G1 phase compared with controls (n=4-8). This is the
      first evidence for loop diuretic inhibition of airway smooth muscle cell
      proliferation. NKCC cotransporter inhibition impeded G1-S phase transition
      without facilitating cell death. Thus although inhibition by loop diuretics
      relaxes airway smooth muscle, the NKCC cotransporter may have a more important
      role in cell proliferation regulation.

PMID- 15155269
TI  - Therapeutic gene transfer to dystrophic diaphragm by an adenoviral vector deleted
      of all viral genes.
AB  - Duchenne muscular dystrophy is caused by defects in the dystrophin gene, and the
      mdx mouse is the most frequently employed genetic model of this disease. It is
      well known that different muscle groups do not respond in the same way to
      dystrophin deficiency. In particular, the mdx mouse diaphragm exhibits severe
      morphological and functional changes not found in other mdx muscles. Use of early
      generation adenoviral vectors to deliver genes to the diaphragm in
      immunocompetent mdx mice has been associated with substantial functional toxicity
      and a rapid loss of transgene expression. Here we determined the response to
      dystrophin gene replacement in the mdx diaphragm using a "gutted" adenoviral
      vector that contains the coding sequence of two full-length dystrophin genes and
      is deleted of most viral DNA sequences. At 1 wk postdelivery of the vector, 23.6
      +/- 4% of total fibers in the injected diaphragm bundle expressed dystrophin at
      the sarcolemma, which remained stable over the study duration of 30 days without
      the need for continuous immunosuppression. Treated diaphragms showed a
      significantly improved resistance to the abnormal force deficits induced by high
      stress muscle contractions, the latter being a functional hallmark of dystrophin
      deficient muscle. This functional amelioration was achieved despite the presence
      of mildly increased inflammation (CD4+ and CD8+ lymphocytes) within the vector
      treated diaphragms. To our knowledge, this is the first demonstration that a
      viral vector can achieve reversal of functional abnormalities in the dystrophic
      diaphragm via therapeutic dystrophin gene transfer without the need for sustained
      immunosuppressive therapy.

PMID- 15155268
TI  - Chronic endothelin A receptor blockade in lambs with increased pulmonary blood
      flow and pressure.
AB  - Endothelin receptor blockade is an emerging therapy for pulmonary hypertension.
      However, hemodynamic and structural effects and potential changes in endogenous
      nitric oxide (NO)-cGMP and endothelin-1 signaling of chronic endothelin A
      receptor blockade in pulmonary hypertension secondary to congenital heart disease
      are unknown. Therefore, the objectives of this study were to determine
      hemodynamic and structural effects and potential changes in endogenous NO-cGMP
      and endothelin-1 signaling of chronic endothelin A receptor blockade in a lamb
      model of increased pulmonary blood flow following in utero placement of an
      aortopulmonary shunt. Immediately after spontaneous birth, shunt lambs were
      treated lifelong with either an endothelin A receptor antagonist (PD-156707) or
      placebo. At 4 wk of age, PD-156707-treated shunt lambs (n = 6) had lower
      pulmonary vascular resistance and right atrial pressure than placebo-treated
      shunt lambs (n = 8, P < 0.05). Smooth muscle thickness or arterial number per
      unit area was not different between the two groups. However, the number of
      alveolar profiles per unit area was increased in the PD-156707-treated shunt
      lambs (190.7 +/- 5.6 vs. 132.9 +/- 10.0, P < 0.05). Plasma endothelin-1 and cGMP
      levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin
      converting enzyme-1, endothelin A, and endothelin B receptor protein levels were
      similar in both groups. We conclude that chronic endothelin A receptor blockade
      attenuates the progression of pulmonary hypertension and augments alveolar growth
      in lambs with increased pulmonary blood flow.

PMID- 15155270
TI  - Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium
      via the type 2 receptor.
AB  - We previously reported that angiotensin II stimulates an increase in nitric oxide
      production in pulmonary artery endothelial cells. The aims of this study were to
      determine which receptor subtype mediates the angiotensin II-dependent increase
      in nitric oxide production and to investigate the roles of the angiotensin type 1
      and type 2 receptors in modulating angiotensin II-dependent vasoconstriction in
      pulmonary arteries. Pulmonary artery endothelial cells express both angiotensin
      II type 1 and type 2 receptors as assessed by RT-PCR, Western blot analysis, and
      flow cytometry. Treatment of the endothelial cells with PD-123319, a type 2
      receptor antagonist, prevented the angiotensin II-dependent increase in nitric
      oxide synthase mRNA, protein levels, and nitric oxide production. In contrast,
      the type 1 receptor antagonist losartan enhanced nitric oxide synthase mRNA
      levels, protein expression, and nitric oxide production. Pretreatment of the
      endothelial cells with either PD-123319 or an anti-angiotensin II antibody
      prevented this losartan enhancement of nitric oxide production. Angiotensin II
      dependent enhanced hypoxic contractions in pulmonary arteries were blocked by the
      type 1 receptor antagonist candesartan; however, PD-123319 enhanced hypoxic
      contractions in angiotensin II-treated endothelium-intact vessels. These data
      demonstrate that angiotensin II stimulates an increase in nitric oxide synthase
      mRNA, protein expression, and nitric oxide production via the type 2 receptor,
      whereas signaling via the type 1 receptor negatively regulates nitric oxide
      production in the pulmonary endothelium. This endothelial, type 2 receptor
      dependent increase in nitric oxide may serve to counterbalance the angiotensin II
      dependent vasoconstriction in smooth muscle cells, ultimately regulating
      pulmonary vascular tone.

PMID- 15155271
TI  - CpG DNA-mediated immune response in pulmonary endothelial cells.
AB  - Although the CpG DNA immune response mediated by Toll-like receptor 9 (TLR9) has
      been extensively studied in a number of immune cells, the response to CpG DNA in
      endothelial cells (EC) is not well understood. In this study, we show that both
      mouse and rat lung EC display constitutive expression of TLR9 mRNA. Exposure to
      CpG DNA induced a potent proinflammatory response as manifested by an increased
      expression of IL-8 and ICAM-1 in mouse pulmonary EC. The proinflammatory response
      was sensitive to chloroquine, consistent with a role of endosomal contribution. A
      role for p38 MAPK and NF-kappaB pathway was apparent as the response was
      sensitive to inhibitors of p38 MAPK and NF-kappaB but was not affected by
      inhibitors of ERK1/2. A synergistic effect of CpG DNA and LPS on the inflammatory
      response is consistent with multiple TLR interaction in EC. This study suggests a
      possible role for CpG DNA-mediated EC immune response in the host defense system.
      It also has important implications in plasmid DNA-mediated pulmonary endothelium
      gene transfer.

PMID- 15155273
TI  - The chemokine receptor CXCR3 and its splice variant are expressed in human airway
      epithelial cells.
AB  - Activation of the chemokine receptor CXCR3 by its cognate ligands induces several
      differentiated cellular responses important to the growth and migration of a
      variety of hematopoietic and structural cells. In the human respiratory tract,
      human airway epithelial cells (HAEC) release the CXCR3 ligands Mig/CXCL9, IP
      10/CXCL10, and I-TAC/CXCL11. Simultaneous expression of CXCR3 by HAEC would have
      important implications for the processes of airway inflammation and repair.
      Accordingly, in the present study we sought to determine whether HAEC also
      express the classic CXCR3 chemokine receptor CXCR3-A and its splice variant CXCR3
      B and hence may respond in autocrine fashion to its ligands. We found that
      cultured HAEC (16-HBE and tracheocytes) constitutively expressed CXCR3 mRNA and
      protein. CXCR3 mRNA levels assessed by expression array were approximately 35% of
      beta-actin expression. In contrast, CCR3, CCR4, CCR5, CCR8, and CX3CR1 were <5%
      beta-actin. Both CXCR3-A and -B were expressed. Furthermore, tracheocytes freshly
      harvested by bronchoscopy stained positively for CXCR3 by immunofluorescence
      microscopy, and 68% of cytokeratin-positive tracheocytes (i.e., the epithelial
      cell population) were positive for CXCR3 by flow cytometry. In 16-HBE cells,
      CXCR3 receptor density was approximately 78,000 receptors/cell when assessed by
      competitive displacement of 125I-labeled IP-10/CXCL10. Finally, CXCR3 ligands
      induced chemotactic responses and actin reorganization in 16-HBE cells. These
      findings indicate constitutive expression by HAEC of a functional CXC chemokine
      receptor, CXCR3. Our data suggest the possibility that autocrine activation of
      CXCR3 expressed by HAEC may contribute to airway inflammation and remodeling in
      obstructive lung disease by regulating HAEC migration.

PMID- 15155272
TI  - Sildenafil alters calcium signaling and vascular tone in pulmonary arteries from
      chronically hypoxic rats.
AB  - Sildenafil, a potent type 5 nucleotide-dependent phosphodiesterase (PDE)
      inhibitor, has been recently proposed as a therapeutic tool to treat or prevent
      pulmonary artery hypertension (PAHT). We thus studied the effect of sildenafil on
      both the calcium signaling of isolated pulmonary artery smooth muscle cells
      (PASMCs) and the reactivity of pulmonary artery (PA) obtained from chronic
      hypoxia (CH)-induced pulmonary hypertensive rats compared with control (normoxic)
      rats. CH rats were maintained in an hypobaric chamber (50.5 kPa) for 3 wk leading
      to full development of PAHT. Intracellular calcium concentration ([Ca2+]i) was
      measured in PASMCs loaded with the calcium fluorophore indo 1. Unlike in control
      rats, sildenafil (10-100 nM) decreased the resting [Ca2+]i value in PASMCs
      obtained from CH rats. In PASMCs from both control and CH rats, sildenafil
      concentration dependently inhibited the [Ca2+]i response induced by G-coupled
      membrane receptor agonists such as angiotensin II and phenylephrine but had no
      effect on the amplitude of the [Ca2+]i response induced by caffeine. Sildenafil
      (0.1 nM-1 microM) concentration dependently reduced basal PA tone that is present
      in CH rats and relaxed PA rings precontracted with phenylephrine in both control
      and CH rats. These data show that sildenafil is a potent pulmonary artery
      relaxant in CH rats and that it normalizes CH-induced increases in resting
      [Ca2+]i and basal tone. Consequently, pharmacological inhibition of sildenafil
      sensitive PDE5 downregulates the Ca2+ signaling pathway involved in this model of
      pulmonary hypertension.

PMID- 15155274
TI  - Molecular identification and characterization of three isoforms of tachykinin
      NK(1)-like receptors in the cane toad Bufo marinus.
AB  - The tachykinin peptide bufokinin, isolated from the cane toad intestine, is
      important in intestinal and cardiovascular regulation in the toad. In this study,
      three tachykinin NK(1)-like receptor isoforms, bNK(1)-A, bNK(1)-B, and bNK(1)-C,
      encoding proteins of 309, 390, and 371 amino acids, respectively, were cloned
      from the toad brain and intestine. These isoforms differ only at the
      intracellular COOH terminus. The bNK(1)-A and bNK(1)-B isoforms are similar to
      the truncated and full-length forms of the mammalian NK(1) receptor, whereas
      bNK(1)-C is unique and does not correspond to any previously described receptor.
      RT-PCR studies demonstrated that three isoform transcripts are widely distributed
      in the toad with high expression in gut, spinal cord, brain, lung, and skeletal
      muscle. When expressed in COS-7 cells, bufokinin showed similar high affinity
      (IC(50) 0.6-0.8 nM) in competing for (125)I-labeled Bolton-Hunter bufokinin
      binding at all receptors, but the binding affinities of substance P (SP) and
      neurokinin A (NKA) were very different at each isoform. When expressed in Xenopus
      oocytes, the truncated isoform, bNK(1)-A, was inactive, whereas bNK(1)-B and
      bNK(1)-C produced changes in chloride current when stimulated by tachykinins
      (minimum concentrations: bufokinin, 0.1 nM; SP, 1 nM; and NKA, 10 nM). A marked
      desensitization of the response was seen to subsequent applications of
      tachykinins, as experienced by the mammalian NK(1) receptor. In summary, our
      study describing three isoforms of NK(1)-like receptor from the toad suggests
      that the alternative splicing of NK(1) receptor is a physiologically conserved
      mechanism and raises a fundamental question as to the physiological role of each
      isoform.

PMID- 15155275
TI  - Low-dose furosemide modulates taste responses in the nucleus of the solitary
      tract of the rat.
AB  - Taste-evoked neural responses in the nucleus of the solitary tract (NST) are
      subject to both excitatory and inhibitory modulation by physiological conditions
      that influence ingestion. Treatments that induce sodium appetite predominantly
      reduce NST gustatory responsiveness to sapid stimuli. When sodium appetite is
      aroused with 10 mg of the diuretic furosemide (Furo), however, NST gustatory
      neurons exhibit an enhanced responsiveness to NaCl. In addition to inducing a
      sodium appetite, 10 mg Furo supports a conditioned taste aversion (CTA). A lower,
      2-mg dose of Furo induces an equivalent sodium appetite, but not a CTA. To
      determine whether the anomalous electrophysiological results reflected the
      adverse effects of the 10-mg dose, we replicated the original experiment but
      instead used 2 mg of Furo. In chronically prepared, lightly anesthetized rats,
      the responses of 49 single NST neurons to 12 taste stimuli were recorded after
      subcutaneous injections of either 2 mg Furo or saline. There was no effect of
      treatment on NST neural responses to the four standard taste stimuli. In the NaCl
      concentration series, however, 2 mg Furo evoked significantly higher responses to
      the two highest concentrations of NaCl. There was no effect of treatment in the
      sucrose concentration series. Thus, unlike other methods that induce a sodium
      appetite, Furo increases NST neural responsiveness to NaCl. At least as far as
      the first central relay, sodium appetite apparently does not depend on specific
      changes in the sensory neural code for taste.

PMID- 15155276
TI  - A long-term high-protein diet markedly reduces adipose tissue without major side
      effects in Wistar male rats.
AB  - Although there is a considerable interest of high-protein, low-carbohydrate diets
      to manage weight control, their safety is still the subject of considerable
      debate. They are suspected to be detrimental to the renal and hepatic functions,
      calcium balance, and insulin sensitivity. However, the long-term effects of a
      high-protein diet on a broad range of parameters have not been investigated. We
      studied the effects of a high-protein diet in rats over a period of 6 mo. Forty
      eight Wistar male rats received either a normal-protein (NP: 14% protein) or high
      protein (HP: 50% protein) diet. Detailed body composition, plasma hormones and
      nutrients, liver and kidney histopathology, hepatic markers of oxidative stress
      and detoxification, and the calcium balance were investigated. No major
      alterations of the liver and kidneys were found in HP rats, whereas NP rats
      exhibited massive hepatic steatosis. The calcium balance was unchanged, and
      detoxification markers (GSH and GST) were enhanced moderately in the HP group. In
      contrast, HP rats showed a sharp reduction in white adipose tissue and lower
      basal concentrations of triglycerides, glucose, leptin, and insulin. Our study
      suggests that the long-term consumption of an HP diet in male rats has no
      deleterious effects and could prevent metabolic syndrome.

PMID- 15155277
TI  - Thyroid hormone induces erythropoietin gene expression through augmented
      accumulation of hypoxia-inducible factor-1.
AB  - Oxygen is of vital importance for the metabolism and function of all cells in the
      human body. Hypoxia, the reduction of oxygen supply, results in adaptationally
      appropriate alterations in gene expression through the activation of hypoxia
      inducible factor 1 (HIF-1) to overcome any shortage of oxygen. Thyroid hormones
      are required for normal function of nearly all tissues, with major effects on
      oxygen consumption and metabolic rate. Thyroid hormones have been found to
      augment the oxygen capacity of the blood by increasing the production of
      erythropoietin (EPO) and to improve perfusion by vasodilation through the
      augmented expression of adrenomedullin (ADM). Because the hypoxic expression of
      both genes depends on HIF-1, we studied the influence of thyroid hormone on HIF-1
      activation in the human hepatoma cell line HepG2 under normoxic and hypoxic
      conditions. We found that thyroid hormones increased HIF-1alpha protein
      accumulation by increasing HIF-1alpha protein synthesis rather than attenuating
      its proteasomal degradation. HIF-1alpha expression directly correlated with
      augmented HIF-1 DNA binding and transcriptional activity of luciferase reporter
      plasmids, whereas HIF-1beta levels remained unaffected. Knocking down HIF-1alpha
      by short interfering RNA (siRNA) clearly demonstrated that thyroid hormone
      induced target gene expression required the presence of HIF-1. Although an
      increased association of the two known coactivators of HIF-1, p300 and SRC-1, was
      found, thyroid hormone did not affect the activity of the isolated COOH-terminal
      transactivating domain of HIF-1alpha. Increased synthesis of HIF-1alpha may
      contribute to the adaptive response of increased oxygen demand under hyperthyroid
      conditions.

PMID- 15155279
TI  - Direct regulation of lipolysis by interleukin-15 in primary pig adipocytes.
AB  - We recently provided evidence that interleukin-15 (IL-15) is expressed lowly in
      the pig adipocyte and that interferon-gamma (IFN-gamma) markedly increases this
      expression through a pathway regulated in part by protein kinase C. In the
      present study, we tested the hypothesis that IL-15 acts directly on the adipocyte
      to regulate lipid accretion by enhancing lipolysis or suppressing lipogenesis.
      Using recombinant porcine IL-15, we determined that this cytokine stimulates
      lipolysis in a dose-dependent manner (P < 0.001). Furthermore, comparative
      studies with other cytokines showed that IL-15 is more potent in its acute
      stimulation of lipolysis than either TNF-alpha, IL-6, or LPS (P < 0.001). When
      specific inhibitors of protein kinase A or Janus kinase are present, the
      lipolytic effect of IL-15 is attenuated (P < 0.01). These data indicate that, in
      addition to its regulation of muscle protein accretion and T-cell growth and
      development, IL-15 also targets the adipocyte directly to alter stimulate
      lipolysis. Thus, when induced by IFN-gamma or other inflammatory mediators, IL-15
      may be a significant homeorhetic factor that mobilizes and directs energy away
      from the adipocyte to other cells during the acute phase of the inflammatory
      response.

PMID- 15155278
TI  - Antisense oligodeoxynucleotides directed against a novel angiotensinogen mRNA
      stabilizing protein reduce blood pressure in spontaneously hypertensive rats.
AB  - We have previously reported that hypertension in the young spontaneously
      hypertensive rat (SHR) is associated with an elevation in tissue angiotensinogen
      and a novel polysomal protein known to stabilize angiotensinogen mRNA. In our
      current study we determined the role of the mRNA-stabilizing protein in the
      regulation of tissue angiotensinogen expression and mean arterial pressure (MAP)
      in the SHR utilizing antisense oligodeoxynucleotide (AON) inhibition. Three AONs
      (RNASTAAS1, position 31-50; RNASTAAS2, position 21-40; RNASTAAS3, position 143
      162 of the cDNA coding for the polysomal protein) were administered intravenously
      (dose 450, 900, and 1,800 microg/kg; 1 dosage/day over 3 days) in conscious,
      chronically instrumented male SHRs at the age of 7 wk. Control SHRs received
      corresponding scrambled oligodeoxynucleotide sequences (SCR1, SCR2, SCR3). Each
      animal received the increasing dose schedule. RNASTAAS2 resulted in a reduced
      expression of the polysomal protein to 21% (liver), 12% (brain), 27% (heart), 18%
      (renal cortex), and 22% (renal medulla) of control. Angiotensinogen expression
      was inhibited to 54% (liver), 41% (brain), 68% (heart), 52% (renal cortex), and
      74% (renal medulla) compared with control SHRs. Decreases in plasma
      concentrations of angiotensinogen and plasma renin activities were associated
      with a significant decrease in MAP from 147 +/- 6 mmHg (after SCR2) to 106 +/- 4
      mmHg after RNASTAAS2. The effects of the two other AONs on MAP were less
      (RNASTAAS1, -31 mmHg; RNASTAAS3, -16 mmHg) with corresponding decreases in mRNAs
      coding for angiotensinogen and the polysomal protein. A significant decrease in
      intracellular concentrations of the polysomal protein accompanied AON inhibition.
      The magnitude of effects (-15 to -41 mmHg) was comparable to the effects of
      captopril (100 mg x kg(-1) x day(-1) for 3 days: -32 mmHg) and an AT(1) receptor
      antagonist (L-158809, 1.5 mg x kg(-1) x day(-1) for 3 days: -36 mmHg). These data
      suggest an important role of the mRNA-stabilizing protein for hepatic and
      extrahepatic angiotensinogen expression and MAP in the SHR.

PMID- 15155280
TI  - Entrainment of the master circadian clock by scheduled feeding.
AB  - The master circadian clock, located in the mammalian suprachiasmatic nuclei
      (SCN), generates and coordinates circadian rhythmicity, i.e., internal
      organization of physiological and behavioral rhythms that cycle with a near 24-h
      period. Light is the most powerful synchronizer of the SCN. Although other
      nonphotic cues also have the potential to influence the circadian clock, their
      effects can be masked by photic cues. The purpose of this study was to
      investigate the ability of scheduled feeding to entrain the SCN in the absence of
      photic cues in four lines of house mouse (Mus domesticus). Mice were initially
      housed in 12:12-h light/dark cycle with ad libitum access to food for 6 h during
      the light period followed by 4-6 mo of constant dark under the same feeding
      schedule. Wheel running behavior suggested and circadian PER2 protein expression
      profiles in the SCN confirmed entrainment of the master circadian clock to the
      onset of food availability in 100% (49/49) of the line 2 mice in contrast to only
      4% (1/24) in line 3 mice. Mice from line 1 and line 4 showed intermediate levels
      of entrainment, 57% (8/14) and 39% (7/18), respectively. The predictability of
      entrainment vs. nonentrainment in line 2 and line 3 and the novel entrainment
      process provide a powerful tool with which to further elucidate mechanisms
      involved in entrainment of the SCN by scheduled feeding.

PMID- 15155281
TI  - Endothelial monocyte-activating polypeptide II causes NOS-dependent pulmonary
      artery vasodilation: a novel effect for a proinflammatory cytokine.
AB  - Endothelial monocyte-activating polypeptide (EMAP) II is a novel proinflammatory
      cytokine that is released from apoptotic and hypoxic cells. The purpose of this
      study was to determine the effect of EMAP II on the pulmonary artery (PA) and to
      characterize its mechanism of action. To study this, isolated PA rings from adult
      male Sprague-Dawley rats were suspended on steel hooks connected to force
      transducers and immersed in 37 degrees C organ baths containing modified Krebs
      Henseleit solution. After equilibration, force displacement of phenylephrine
      preconstricted PA was measured in response to EMAP II. Experiments were performed
      in endothelium-intact rings, endothelium-denuded rings, and in the presence of
      the NOS inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME). Pulmonary
      artery rings were then subjected to quantitative PCR analysis for inducible NOS
      (iNOS) mRNA. EMAP II caused a maximal vasodilation of 251 +/- 30.7 mg in
      endothelium-intact PA. EMAP II caused no vasodilation in endothelium-denuded and
      l-NAME-treated PA (20 +/- 14.0 mg and 17.5 +/- 7.5 mg, respectively, P < 0.001
      vs. endothelium intact). In addition to its vasoactive properties, EMAP II
      increased PA iNOS mRNA twofold compared with controls. These results demonstrate
      that 1) EMAP II causes PA vasodilation; 2) EMAP II-mediated PA vasodilation is
      endothelium dependent and NOS dependent; and 3) EMAP II upregulates iNOS mRNA
      expression in PA. This report constitutes the first demonstration of EMAP II's
      effects on the pulmonary artery, its mechanism of action, and represents the
      identification of the first proinflammatory cytokine to cause PA vasodilation.

PMID- 15155282
TI  - Cerebral carbohydrate cost of physical exertion in humans.
AB  - Above a certain level of cerebral activation the brain increases its uptake of
      glucose more than that of O(2), i.e., the cerebral metabolic ratio of
      O(2)/(glucose + 12 lactate) decreases. This study quantified such surplus brain
      uptake of carbohydrate relative to O(2) in eight healthy males who performed
      exhaustive exercise. The arterial-venous differences over the brain for O(2),
      glucose, and lactate were integrated to calculate the surplus cerebral uptake of
      glucose equivalents. To evaluate whether the amount of glucose equivalents
      depends on the time to exhaustion, exercise was also performed with beta(1)
      adrenergic blockade by metoprolol. Exhaustive exercise (24.8 +/- 6.1 min; mean +/
      SE) decreased the cerebral metabolic ratio from a resting value of 5.6 +/- 0.2
      to 3.0 +/- 0.4 (P < 0.05) and led to a surplus uptake of glucose equivalents of 9
      +/- 2 mmol. beta(1)-blockade reduced the time to exhaustion (15.8 +/- 1.7 min; P
      < 0.05), whereas the cerebral metabolic ratio decreased to an equally low level
      (3.2 +/- 0.3) and the surplus uptake of glucose equivalents was not significantly
      different (7 +/- 1 mmol; P = 0.08). A time-dependent cerebral surplus uptake of
      carbohydrate was not substantiated and, consequently, exhaustive exercise
      involves a brain surplus carbohydrate uptake of a magnitude comparable with its
      glycogen content.

PMID- 15155283
TI  - CCK-induced inhibition of presympathetic vasomotor neurons: dependence on
      subdiaphragmatic vagal afferents and central NMDA receptors in the rat.
AB  - Systemic administration of cholecystokinin (CCK) inhibits a subpopulation of
      rostral ventrolateral medulla (RVLM) presympathetic vasomotor neurons. This study
      was designed to determine whether this effect involved subdiaphragmatic vagal
      afferents and/or central N-methyl-d-aspartic acid (NMDA) receptors. Recordings
      were made from CCK-sensitive RVLM presympathetic vasomotor neurons in halothane
      anesthetized, paralyzed male Sprague-Dawley rats. The responses of the neurons to
      CCK (2 and 4 microg/kg iv), phenylephrine (PE; 5 microg/kg iv), and
      phenylbiguanide (PBG; 5 microg/kg iv) were tested before and after application of
      the local anesthetic lidocaine (2% wt/vol gel; 1 ml) to the subdiaphragmatic vagi
      at the level of the esophagus. In seven separate experiments, lidocaine markedly
      reduced the inhibitory effects of CCK on RVLM presympathetic neuronal discharge
      rate. In other experiments, the effect of systemic administration of dizocilpine
      (1 mg/kg iv), a noncompetitive antagonist at NMDA receptor ion channels, on the
      RVLM presympathetic neuronal responses to CCK, PBG, and PE was tested. In all
      cases (n = 6 neurons in 6 individual rats), dizocilpine inhibited the effects of
      CCK, PBG, and PE on RVLM presympathetic neuronal discharge. These results suggest
      that the effects of systemic CCK on the discharge of RVLM presympathetic neurons
      is mediated via an action on receptors located on subdiaphragmatic vagal
      afferents. Furthermore, the data suggest that CCK activates a central pathway
      involving NMDA receptors to produce inhibition of RVLM presympathetic neuronal
      discharge.

PMID- 15155284
TI  - Effects of age on brachial artery myogenic responses in humans.
AB  - The myogenic response, the inherent ability of blood vessels to rapidly respond
      to changes in transmural pressure, is involved in local blood flow
      autoregulation. Animal studies suggest that aging impairs the myogenic response.
      The purpose of this study was to compare the effects of changes in transmural
      pressure on mean blood velocity (MBV, cm/s) in young and older subjects. Twelve
      younger men and women (25 +/- 1 yr) were gender and body composition matched to
      twelve older men and women (65 +/- 1 yr). A specially designed tank raised or
      lowered forearm pressure by 50 mmHg within 0.2 s. Brachial artery MBV was
      measured directly above the site of forearm pressure change using Doppler
      methods. In response to increasing transmural pressure (i.e., release of +50
      mmHg), older subjects compared with younger subjects had significantly lower peak
      MBV (Delta 12.43 +/- 1.16 vs. Delta 17.97 +/- 2.01 cm/s; P < 0.05), reduced rates
      in the dynamic fall of MBV after peak values were achieved (vasoconstriction) (
      1.88 +/- 0.17 vs. -2.90 +/- 0.28 cm.s(-1).s(-1); P < 0.05), and lower MBV values
      with sustained suction. In response to decreasing transmural pressure (i.e.,
      change to +50 mmHg), there was a significantly greater increase in MBV (Delta
      peak flow from trough 7.71 +/- 1.32 vs. 4.38 +/- 0.71 cm/s; P < 0.05) and a trend
      toward a greater rate of rise in MBV (vasodilation; 1.61 +/- 0.29 vs. 0.96 +/-
      0.21 cm.s(-1).s(-1); P = 0.08) in the older subjects. Older subjects compared
      with the younger subjects exhibited decreased dynamic vasoconstriction, enhanced
      steady-state constriction, as well as evidence for enhanced dynamic vasodilation
      responses to sustained alterations in forearm transmural pressure.

PMID- 15155285
TI  - (Mis)use of factor analysis in the study of insulin resistance syndrome.
AB  - Over the last decade, factor analysis has been used increasingly to describe
      patterns of simultaneous occurrence of the central components of the insulin
      resistance syndrome. In this paper, the authors describe factor analysis, review
      studies that have used factor analysis to examine the insulin resistance
      syndrome, and explore how factor analysis might be used to increase our
      understanding of this syndrome. Most studies that they reviewed gave vague
      reasons for using factor analysis and did not demonstrate an understanding of the
      use and limitations of this statistical method. Confirmatory factor analysis
      based on sound theoretical concepts and a clear understanding of the statistical
      methods may provide some insights into the pathophysiology of the syndrome.
      However, to date none of the studies has adopted this approach, and other
      statistical approaches and study designs are likely to provide greater
      understanding of the syndrome.

PMID- 15155286
TI  - Caregiving stress, endogenous sex steroid hormone levels, and breast cancer
      incidence.
AB  - Stress is hypothesized to be a risk factor for breast cancer. The authors
      examined associations of hours of, and self-reported levels of stress from,
      informal caregiving with prospective breast cancer incidence. Cross-sectional
      analyses of caregiving and endogenous sex steroid hormones were also conducted.
      In 1992 or 1996, 69,886 US women from the Nurses' Health Study, aged 46-71 years
      at baseline, answered questions on informal caregiving; 1,700 incident breast
      cancer cases accrued over follow-up to 2000. A subset of 665 postmenopausal women
      not taking exogenous hormones returned a blood sample in 1990. Numbers of hours
      of care provided to an ill adult or to a child were each summed and analyzed as 0
      (reference), 1-14, and >/=15 per week. Cox proportional hazards models were used
      in prospective analyses and linear models in cross-sectional analyses. High
      numbers of caregiving hours and self-reported stress did not predict a higher
      incidence of breast cancer. However, compared with women providing no adult care,
      women providing >/=15 hours of adult care (median, 54) had significantly lower
      levels of estradiol (geometric mean, 9.21 pg/ml vs. 7.46 pg/ml (95% confidence
      interval: 6.36, 8.76)) and bioavailable estradiol (geometric mean, 1.86 pg/ml vs.
      1.35 pg/ml (95% confidence interval: 1.00, 1.82)). Stress from caregiving did not
      appear to increase breast cancer risk.

PMID- 15155288
TI  - Sudden death and recurrent ischemic events after myocardial infarction in the
      community.
AB  - As myocardial infarction (MI) hospital fatalities decline, survivors are
      candidates for recurrent events. However, little is known about morbidity after
      MI and how it may have changed over time. The authors examined the incidence of
      sudden cardiac death and recurrent ischemic events post-MI to test the hypothesis
      that it has declined over time. MIs were validated by using standardized
      criteria. Sudden cardiac death and recurrent ischemic events (recurrent MI or
      unstable angina) were identified through Olmsted County, Minnesota, community
      medical records and their association with time examined after adjustment for
      age, sex, and comorbidity. Between 1979 and 1998, 2,277 MIs occurred (57% in men;
      mean age, 67 (standard deviation, 14) years). After 3 years, the event-free
      survival rate was 94% (95% confidence interval: 93, 95) for sudden cardiac death
      and 56% (95% confidence interval: 54, 58) for recurrent ischemic events. Both
      outcomes were more frequent with older age and greater comorbidity. The temporal
      decline in both events was of similar magnitude; for an MI occurring in 1998
      versus 1979, risk of subsequent recurrent ischemic events or sudden cardiac death
      declined by 24% (relative risk = 0.76, 95% confidence interval: 0.63, 0.93).
      Thus, in the community, recurrent ischemic events are frequent post-MI, while
      sudden cardiac death is less common. Their incidence declined over time,
      supporting the notion that contemporary treatments effectively improve outcomes
      after MI.

PMID- 15155289
TI  - Individual- and area-level socioeconomic status variables as predictors of
      mortality in a cohort of 179,383 persons.
AB  - The authors have studied whether area-level socioeconomic status predicts
      mortality independently of individual-level socioeconomic status in 179,383
      persons in the American Cancer Society Nutrition Cohort, followed for mortality
      from 1992 to 2000 (17,383 deaths). They used an area-level variable based on
      census blocks that was an average of home value, income, education, and
      occupation. Education was the individual-level socioeconomic status variable. The
      authors studied socioeconomic status-mortality trends with each socioeconomic
      status variable adjusted for the other. For all causes, an individual's education
      was strongly and inversely associated with mortality; a weak but significant
      inverse trend was also present for area-level socioeconomic status. A similar
      pattern was seen for all-vascular disease. For all cancers, there was again a
      significant inverse trend with education but no trend with area-level
      socioeconomic status. Adjustment for conventional (non-socioeconomic status)
      individual-level risk factors diminished the effect of both socioeconomic status
      variables, although significant trends remained for men between education and all
      cause, all-cancer, and all-vascular disease mortality. Study data indicate that
      the predictive value of area-level socioeconomic status variables varies by cause
      of death but is less important than individual-level socioeconomic status
      variables. Multivariate models that consider socioeconomic status as a potential
      confounder may not need to consider area-level socioeconomic status if data are
      available on individual-level education.

PMID- 15155290
TI  - Birth rate among patients with epilepsy: a nationwide population-based cohort
      study in Finland.
AB  - Few reports on population-based studies of birth rate among epilepsy patients
      have been published. In most previous studies, fertility has been lower among
      epilepsy patients than in the rest of the population. However, conflicting
      results have also been reported. Because of small samples and selective material,
      the generalizability of these results is also limited. The authors conducted a
      population-based cohort study of birth rate (1985-2001) in a nationwide Finnish
      cohort of patients with newly diagnosed epilepsy and a population-based reference
      cohort. All patients (n = 14,077) approved as eligible for reimbursement for
      antiepileptic medication from the Social Insurance Institution of Finland (KELA)
      for the first time between 1985 and 1994 were identified from the KELA database.
      A reference cohort (n = 29,828) was identified from the Finnish Population
      Register Center, with frequency-matching on age. Information on follow-up status
      and livebirths were also obtained from the Finnish Population Register Center.
      The birth rate was lower in patients with epilepsy than in the reference cohort
      among both men (hazard ratio = 0.58, 95% confidence interval: 0.54, 0.62) and
      women (hazard ratio = 0.88, 95% confidence interval: 0.83, 0.93). There were a
      clear decreasing trend by age at observation in men with epilepsy and a moderate
      decreasing trend by age at start of follow-up in women with epilepsy.

PMID- 15155287
TI  - Long-term plasma lipid changes associated with a first birth: the Coronary Artery
      Risk Development in Young Adults study.
AB  - Previous studies have reported declines in high density lipoprotein (HDL)
      cholesterol 1-2 years after pregnancy. In 1986-1996, the authors prospectively
      examined the association between childbearing and changes in fasting plasma
      lipids (low density lipoprotein, HDL, and total cholesterol; triglycerides) among
      1,952 US women (980 Black, 972 White) in the Coronary Artery Risk Development in
      Young Adults study. Repeated-measures multiple linear regression was used to
      examine lipid changes over three time intervals (baseline to years 5, 7, and 10)
      in time-dependent follow-up groups: P0 (0 pregnancies), P1 (>/=1
      miscarriages/abortions), B1 (1 birth), and B2 (>/=2 births). Means stratified by
      race and baseline parity (nulliparous or parous) were fully adjusted for study
      center, time, height, baseline diet, and other baseline and time-dependent
      covariates (age, smoking, education, weight, waist circumference, alcohol intake,
      oral contraceptive use, physical activity, short pregnancies). For both races,
      fully adjusted HDL cholesterol declines of -3 to -4 mg/dl were associated with a
      first birth versus no pregnancies during follow-up (p < 0.001). Higher-order
      births were not associated with greater declines in HDL cholesterol (B2 similar
      to B1, no association among women parous at baseline). In Whites, total and low
      density lipoprotein cholesterol declines were associated with follow-up births.
      HDL cholesterol declines of -3 to -4 mg/dl after a first birth persisted during
      the 10 years of follow-up independent of weight, central adiposity, and selected
      behavior changes.

PMID- 15155291
TI  - In-theater hospitalizations of US and allied personnel during the 1991 Gulf War.
AB  - The postwar morbidity of Gulf War veterans has been closely examined. However,
      data have not been available to evaluate morbidity suffered during the 1991 Gulf
      War. In this report, the authors examine archived records of hospitalizations in
      US military facilities in the Kuwaiti theater of operations or those medically
      evacuated to facilities in Europe. Using multivariable logistic regression
      modeling, the authors determined that service personnel at greatest odds for "in
      theater" hospitalization were enlisted, female, White, Reservist, Army, and
      health care workers. No increase in odds was observed for oil well fire smoke
      exposure or possible exposure to the nerve agent hazard areas. Although these
      data may be incomplete, they represent the best-known data reflecting in-theater
      hospitalizations during the Gulf War of 1991 and show remarkable similarities in
      risk factors to those for postwar hospitalization.

PMID- 15155292
TI  - Flexible meta-regression functions for modeling aggregate dose-response data,
      with an application to alcohol and mortality.
AB  - In this paper, the authors describe fractional polynomials and cubic splines with
      which to represent smooth dose-response relations in summarizing meta-analytical
      aggregate data. Use of these two curve-fitting families can help prevent the
      problems arising from inappropriate linearity assumptions. These methods are
      illustrated in the problem of estimating the shape of the dose-response curve
      between alcohol consumption and all-cause mortality risk. The authors considered
      aggregate data from 29 cohort studies investigating this issue (1966-2000). J
      shaped curves with a nadir at approximately 5-7 g/day of alcohol consumption and
      a last protective dose of 47-60 g/day were consistently obtained from fractional
      polynomials and cubic splines. The authors conclude that both of the curve
      fitting families are useful tools with which to explore dose-response
      epidemiologic questions by means of meta-analytical approaches, especially when
      important nonlinearity is anticipated.

PMID- 15155293
TI  - Patterns of consent in epidemiologic research: evidence from over 25,000
      responders.
AB  - Ethical guidelines in the United Kingdom require written consent from
      participants in epidemiologic studies for follow-up or review of medical records.
      This may cause bias in samples used for follow-up or medical record review. The
      authors analyzed data from seven general population surveys conducted in the
      United Kingdom (1996-2002), to which over 25,000 people responded. Associations
      of age, gender, and symptom under investigation with consent to follow-up and
      consent to review of medical records were examined. Consent to follow-up was
      approximately 75-95% among survey responders under age 50 years but fell among
      older people, particularly females. Consent to follow-up was also higher among
      responders who had the symptom under investigation (pooled odds ratio = 1.61, 95%
      confidence interval: 1.36, 1.92). Consent to review of medical records followed a
      similar pattern. Patterns of consent were relatively consistent and represented a
      high proportion of responders. Males, younger people, and subjects reporting the
      symptom under investigation were more likely to give consent, and these groups
      may be overrepresented in follow-up samples or reviews of medical records.
      Although consent is high among responders, the additive effect of nonresponse and
      nonconsent can substantially reduce sample size and should be taken into account
      in epidemiologic study planning.

PMID- 15155294
TI  - Self-assessment of circumcision status by adolescents.
AB  - In epidemiologic studies of the relation between circumcision and sexually
      transmitted infections, it is necessary to rely on self-report of circumcision
      status. The purpose of this 2002 study in Houston, Texas, was to determine
      whether adolescent males could make correct self-reports. During physical
      examinations, adolescents were asked whether they were circumcised. The authors
      then examined the adolescents' genitalia. Circumcision status was recorded as
      complete (glans penis fully exposed), partial (glans partly covered), or
      uncircumcised (glans completely covered). The mean age of the 1,508 subjects was
      15.0 (standard deviation, 1.63) years; 64% were Black, 29% Hispanic, and 7%
      White. Forty-nine percent had full, 1% partial, and 50% no circumcision. Of the
      738 fully circumcised subjects, 512 (69%) considered themselves circumcised, 54
      (7%) considered themselves uncircumcised, and 172 (23%) did not know. Of the 751
      uncircumcised youth, 491 (65%) described themselves as uncircumcised, 27 (4%)
      reported being circumcised, and 233 (31%) did not know. The sensitivity of self
      report among those who thought they knew their status was 90.5%, and the
      specificity was 94.8%; 27% did not know their status. In this population, self
      report of circumcision status did not result in accurate information mainly
      because many adolescents were unsure of their status.

PMID- 15155295
TI  - Validity of self-reported skin screening histories.
AB  - Screening by whole-body clinical skin examination may improve early diagnosis of
      melanoma and reduce mortality, but objective scientific evidence of this is
      lacking. As part of a randomized controlled trial of population screening for
      melanoma in Queensland, Australia, the authors assessed the validity of self
      reported history of whole-body skin examination and factors associated with
      accuracy of recall among 2,704 participants in 2001. Approximately half of the
      participants were known to have undergone whole-body skin examination within the
      past 3 years at skin screening clinics conducted as part of the randomized trial.
      All positive and negative self-reports were compared with screening clinic
      records. Where possible, reports of skin examinations conducted outside the
      clinics were compared with private medical records. The validity of self-reports
      of whole-body skin examination in the past 3 years was high: Concordance between
      self-reports and medical records was 93.7%, sensitivity was 92.0%, and
      specificity was 96.3%. Concordance was lower (74.3%) for self-reports of
      examinations conducted in the past 12 months, and there was evidence of
      "telescoping" in recall for this more recent time frame. In multivariate
      analysis, women and younger participants more accurately recalled their history
      of skin examinations. Participants with a history of melanoma did not differ from
      other participants in their accuracy of recall.

PMID- 15155296
TI  - Re: "flexible matching strategies to increase power and efficiency to detect and
      estimate gene-environment interactions in case-control studies".

PMID- 15155297
TI  - Intrathecal midazolam: an ethical editorial dilemma.

PMID- 15155298
TI  - Preclinical insights into the implementation of intrathecal midazolam: a
      cautionary tale.

PMID- 15155299
TI  - Intrathecal midazolam I: a cohort study investigating safety.
AB  - Despite conflicting evidence regarding the safety of intrathecal midazolam from
      animal investigations, its clinical use is increasing. We investigated the
      potential of intrathecal midazolam to produce symptomatology suggestive of
      neurological damage. This study compared two cohorts of patients who received
      intrathecal anesthesia with or without intrathecal midazolam (2 mg). Eighteen
      risk factors were evaluated with respect to symptoms representing potential
      neurological complications. The definitions of these symptoms were made wide to
      maximize the chance of counting patients with neurological sequelae after
      intrathecal injections. Eleven-hundred patients were followed up prospectively
      during the first postoperative week by a hospital chart review and 1 mo later by
      a mailed questionnaire. Symptoms suggestive of neurological impairment, including
      motor or sensory changes and bladder or bowel dysfunction, were investigated.
      Intrathecal midazolam was not associated with an increased risk of neurologic
      symptoms. In contrast, neurologic symptoms were found to be increased by age >70
      yr (relative risk, 8.72) and the occurrence of a blood-stained spinal tap
      (relative risk, 8.07). The administration of intrathecal midazolam, 2 mg, did not
      increase the occurrence of neurologic or urologic symptoms, as suggested by some
      preclinical animal experimentation. IMPLICATIONS: Intrathecal midazolam provides
      segmental analgesia, but conflicting animal studies have cast doubts on its
      safety. This investigation studied the effect of intrathecal midazolam by
      observing two cohorts of patients. In clinical practice, intrathecal midazolam (2
      mg) did not increase adverse neurological symptoms compared with conventional
      therapies.

PMID- 15155300
TI  - Intrathecal midazolam II: combination with intrathecal fentanyl for labor pain.
AB  - Recent investigations have sought to improve intrathecal analgesia by combining
      opioids with other classes of analgesics. In this study we assessed the ability
      of intrathecal midazolam to increase the potency and duration of the analgesic
      effects of intrathecal fentanyl without causing adverse effects. Thirty
      parturients with cervical dilations 2-6 cm were randomized to receive either
      intrathecal midazolam 2 mg, fentanyl 10 micro g, or both combined to initiate
      analgesia. Pain scores were recorded before and at 5-min intervals for 30 min
      after the injection and then every 30 minutes until the patient requested further
      analgesia. The presence and severity of nausea, emesis, pruritus, headache, and
      sedation, in addition to arterial blood pressure, heart rate, respiratory rate,
      sensory changes to ice, motor impairment, cardiotocograph, and Apgar score were
      also recorded. The parturients were assessed after 2 days and 1 mo for neurologic
      impairment. Preinjection pain scores were unaltered by intrathecal midazolam
      alone and moderately decreased by fentanyl. Intrathecal midazolam increased the
      analgesic effect of fentanyl. No treatment altered cardiorespiratory variables or
      caused motor impairment. The addition of intrathecal midazolam to fentanyl did
      not increase the occurrence of any maternal adverse event or abnormalities on the
      cardiotocograph. We conclude that intrathecal midazolam enhanced the analgesic
      effect of fentanyl without increasing maternal or fetal adverse effects.
      IMPLICATIONS: Treatment of labor pain with epidural injections of local
      anesthetic is complicated by decreases in arterial blood pressure and leg
      weakness. This study showed that a mixture of two drugs, fentanyl and midazolam,
      could provide powerful pain relief when the drugs were given together spinally
      without such side effects.

PMID- 15155301
TI  - Safety of continuous intrathecal midazolam infusion in the sheep model.
AB  - We investigated the safety of midazolam administered by continuous intrathecal
      infusion in relevant animal models. Preservative-free midazolam was delivered to
      sheep and pigs by using implanted infusion systems (SynchroMed pumps plus
      silicone catheters). Sheep received midazolam 5 mg/d (n = 4) or 15 mg/d (n = 7)
      or saline (n = 2) for 43 days at 125 micro L/h. One sheep received 10 mg/d.
      Infusion concentrations ranged from 1.7 to 2.5 mg/mL (5 mg/d) and from 2.5 to 5.0
      mg/mL (15 mg/d). Pigs were evaluated for toxicity only and received 15 mg/d (n =
      2) or saline (n = 1) for 43 days at 125 micro L/h. Behavior, neurologic function,
      and vital signs were documented. Serum and cerebrospinal fluid chemistry and
      cytology were evaluated, and histology was performed on spinal cord tissue.
      Behavior and neurologic function remained normal in all subjects. Gross and
      microscopic evaluation of spinal tissue revealed mild inflammation surrounding
      the catheter tract in both the midazolam-treated and the saline-treated groups.
      This inflammation was likely attributable to the mechanical presence of the
      catheter. These data demonstrate that continuous intrathecal infusion of
      preservative-free midazolam at doses up to 15 mg/d were well tolerated.
      IMPLICATIONS: We investigated the toxicity of preservative-free intrathecal
      midazolam delivered continuously via implanted infusion systems in sheep and
      pigs. Doses of 5-15 mg/d were well tolerated. The lack of neurotoxicity observed
      suggests that intrathecal midazolam may be an alternative for the treatment of
      intractable pain that is unresponsive to opioids.

PMID- 15155302
TI  - The use of intrathecal midazolam in humans: a case study of process.
AB  - Early preclinical work demonstrated the potential role of spinal benzodiazepine
      pharmacology in regulating spinal nociceptive transmission. We review this
      preclinical activity and the evolving implementation of intrathecal midazolam in
      humans for pain management. Important elements in this development for use in
      humans are issues pertinent to safety and the preclinical reports that have
      increased our understanding of intrathecal midazolam toxicity. We seek to
      emphasize the time course of these studies and how they merged to provide
      enabling data that drove the clinical implementation. In the case of midazolam,
      we point to the potential issues that arose when preclinical safety data were
      unreasonably ignored and how consideration of preclinical safety data can serve
      to facilitate drug development by demonstrating reasonable safety profiles that
      document the minimal degree of potential risk to the patient. Issues that are of
      continuing relevance to the use of intrathecal midazolam, including issues of
      formulation and kinetics, are considered. IMPLICATIONS: The intrathecal use of
      midazolam has evolved over 20 years though a combination of preclinical and
      clinical investigations. We review the time course of this development to define
      critical elements that should be pursued in reducing the risk associated with the
      clinical use of a novel spinal drug.

PMID- 15155303
TI  - Moderate-to-severe pain after knee arthroscopy is relieved by intraarticular
      saline: a randomized controlled trial.
AB  - We have previously studied intraarticular (IA) analgesics compared with saline 10
      mL in 2 randomized clinical trials. The patients who were given IA saline
      experienced rapid pain relief. Hypothetically, saline may produce a local
      analgesic effect by cooling or by diluting IA algogenic substances. This
      randomized double-blind study compared the analgesic effect of IA saline 10 mL
      with saline 1 mL, which should be a pure placebo. A soft catheter was left IA in
      79 patients. We included 60 patients who developed moderate-to-severe pain within
      1 h after knee arthroscopy under general anesthesia. A randomized, double-blind
      controlled comparison of IA saline 10 mL with saline 1 mL followed. Outcome
      measures were pain intensity, pain relief, and analgesic consumption. Within 1 h
      pain intensity decreased in both groups from approximately 50 to approximately 27
      on a 0-100 mm visual analog scale. Pain intensity remained low and other pain
      outcome measures were similar during the 36-h observation period. The patients
      experienced equally good pain relief after IA injection of saline 10 mL and 1 mL.
      Our finding of a major placebo effect may have implications for the
      interpretation of previously published placebo-controlled IA analgesia studies.
      IMPLICATIONS: In a randomized controlled trial we showed that pain after knee
      arthroscopy is modest and short-lived and can successfully be treated with
      intraarticular saline as placebo.

PMID- 15155304
TI  - Comparison of percutaneous electrical nerve stimulation with transcutaneous
      electrical nerve stimulation for long-term pain relief in patients with chronic
      low back pain.
AB  - The long-term effect of percutaneous electrical nerve stimulation (PENS) on
      chronic low back pain (LBP) is unclear. We evaluated the number of sessions for
      which PENS should be performed to alleviate chronic LBP and how long analgesia is
      sustained. Patients underwent treatment on a twice-weekly schedule for 8 wk.
      Group A (n = 18) received PENS for 8 wk, group B (n = 17) received PENS for the
      first 4 wk and transcutaneous electrical nerve stimulation (TENS) for the second
      4 wk, and group C (n = 18) received TENS for 8 wk. Pain level, degree of physical
      impairment, and the daily intake of nonsteroidal antiinflammatory drugs (NSAIDs)
      were assessed before the first treatment, 3 days after Week 2, Week 4, and Week 8
      treatments, and at 1 and 2 mo after the sessions. During PENS therapy, the pain
      level decreased significantly from Week 2 in Groups A and B (P < 0.05 or 0.01),
      and physical impairment and required NSAIDs decreased significantly from Week 4
      (P < 0.05 or 0.01) in Group A but only at Week 4 in Group B (P < 0.05 or 0.01).
      These effects were sustained until 1-mo follow-up (P < 0.01) in Group A but not
      in Group B; these effects were not observed at 2-mo follow-up even in Group A. In
      Group C, pain level decreased significantly only at Week 8 (P < 0.05). Our
      results indicate that repeated PENS is more effective than TENS for chronic LBP
      but must be continued to sustain the analgesic effect. IMPLICATIONS: A cumulative
      analgesic effect was observed in patients with chronic low back pain (LBP) after
      repeated percutaneous electrical nerve stimulation (PENS), but this effect
      gradually faded after the treatment was terminated. Results indicate that
      although PENS is effective for chronic LBP, treatments need to be continued to
      sustain analgesia.

PMID- 15155305
TI  - A simple, fast, easy method to identify the evidence base in pain-relief
      research: validation of a computer search strategy used alone to identify quality
      randomized controlled trials.
AB  - Clinicians need a simple, fast, reliable, and inexpensive way of identifying the
      evidence base relevant to their clinical practice. It is often believed that the
      only way to identify all relevant evidence is to perform hand-searches of the
      literature to supplement computer searches; this is complex and labor intensive.
      However, most of quality randomized controlled trials cited in systematic reviews
      in pain medicine are listed in computer databases. We performed two studies to
      investigate the efficiency-in terms of sensitivity, specificity, and precision-of
      three computer search strategies: Optimally Sensitive Search Strategy, which is
      used by the Cochrane Collaboration; RCT.pt, a standard MEDLINE strategy; and
      DBRCT.af, which is a new single-line computer algorithm based on the assumption
      that double-blinded, randomized controlled trials would be indexed with "double
      blind," "random," or variations of these terms in MEDLINE and EMBASE. DBRCT.af
      was found to be highly sensitive (97%) in identifying quality randomized
      controlled trials in pain medicine. The precision (ratio of randomized controlled
      trials to the number of nonrandomized trials identified) was 82%, and the
      specificity in excluding the nonrandomized controlled trials was 98%. We conclude
      that clinicians can now use DBRCT.af to update and conduct de novo systematic
      reviews in pain-relief research. IMPLICATIONS: Quality evidence about what is
      good clinical practice in pain treatment is buried in the medical literature
      among large quantities of other information. This article describes how any
      clinician with access to the Internet can identify those quality studies
      reliably, quickly, and inexpensively.

PMID- 15155307
TI  - The effects of local pentoxifylline and propentofylline treatment on formalin
      induced pain and tumor necrosis factor-alpha messenger RNA levels in the inflamed
      tissue of the rat paw.
AB  - We sought to determine whether local administration of pentoxifylline (PTF) or
      propentofylline (PPTF), which hinders cytokine production, influences pain
      threshold and formalin-induced pain behavior in rats or the level of tumor
      necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) concentrations in the
      inflamed paw tissue. PTF (0.5, 1, or 2 mg) and PPTF (1 or 2 mg) injected
      intraplantarly (i.pl.) had no significant effect on pain threshold. Injection of
      0.1 mL of a 12% formalin solution subcutaneously into the dorsal surface of the
      left hindpaw induced pain behavior (47.6 +/- 4.6 incidents per 5 min), and PTF
      injected at doses of 1 and 2 mg/100 microL i.pl. before (but not after) formalin
      was effective in antagonizing (33.6 +/- 2.5 and 23.6 +/- 3.4 incidents per 5 min,
      respectively) formalin-induced pain behavior. A similar antagonistic effect was
      observed after PPTF treatment at a dose of 2 mg/100 microL; however, in contrast
      to PTF, at a later time point (85-90 min) after the formalin challenge, this
      effect was independent of the scheme of PPTF administration, before or after
      formalin. The effect of PTF on formalin-induced pain behavior did not parallel
      paw volume as measured by plethysmometer; however, PTF per se significantly
      increased the paw volume. Formalin injection significantly increased the TNF
      alpha mRNA level in the inflamed tissue of the rat hind paw (150%). PTF
      administered before, but not after, formalin significantly antagonized (by
      approximately 40%) the observed increase in the level of TNF-alpha mRNA. Our
      study demonstrates and provides biochemical evidence that preemptive inhibition
      of proinflammatory cytokine synthesis by the use of PTF and PPTF,
      phosphodiesterase, and glial activation inhibitors is useful in antagonizing
      hyperalgesia in formalin-induced pain. Moreover, local administration of PTF may
      be a valuable approach to the treatment of inflammatory pain. IMPLICATIONS: This
      study demonstrates and provides biochemical evidence that preemptive inhibition
      of proinflammatory cytokine synthesis by local administration of pentoxifylline
      and propentofylline is useful in antagonizing hyperalgesia in formalin-induced
      pain. Moreover, local administration of pentoxifylline could be regarded as a
      valid approach to the treatment of inflammatory pain.

PMID- 15155308
TI  - The synergistic effect of combined treatment with systemic ketamine and morphine
      on experimentally induced windup-like pain in humans.
AB  - In this study, we evaluated whether combined treatment with ketamine (KET), an N
      methyl-D-aspartate receptor antagonist, and morphine (MO) results in positive
      analgesic effects. Eleven volunteers were exposed to a skin burn injury on the
      leg. The effects of IV KET (9 microg. kg(-1). min(-1); 45 min) and MO (10 microg.
      kg(-1). min(-1); 10 min) alone and in combination, as well as placebo (saline; 10
      min), were studied in a randomized, crossover, double-blinded design. The area of
      secondary hyperalgesia (SH) for mechanical stimulation was diminished by KET as
      compared with placebo. Mechanical pain thresholds were increased severalfold with
      KET and with KET plus MO, both in the primary hyperalgesic (PH; burn injury) and
      SH area. MO infusion showed no effect on the SH area or pain threshold. Windup
      like pain was evaluated by continuous assessment on a visual analog scale during
      30 s of repetitive stimulation (40-g load at 3 Hz) and analyzed as a sum of pain
      scores. The combined treatment (KET plus MO) almost abolished windup-like pain
      both in the PH and the SH areas, an effect that was not present with monotherapy
      with KET or MO. This study provides experimental support for a positive analgesic
      interaction between an N-methyl-D-aspartate receptor antagonist and an opioid on
      central summation of pain. IMPLICATIONS: This is the first experimental study in
      humans to find synergistic analgesic effects with coadministration of the N
      methyl-D-aspartate receptor antagonist ketamine and morphine on pain involving
      central sensitization phenomena.

PMID- 15155309
TI  - The long-term effect of repeated intravenous lidocaine on central pain and
      possible correlation in positron emission tomography measurements.
AB  - Functional neuroimaging suggests that similar brain regions are involved in the
      processing of pain in healthy subjects and in patients with chronic neuropathic
      central pain. We present a patient with chronic neuropathic central pain due to a
      unique lesion to the trigeminal and spinothalamic pathway who had persistent pain
      relief after repeated IV lidocaine infusions. Positron emission tomography scan
      results showed a relative hypoactivity of the left posterolateral thalamus before
      treatment which disappeared after therapy. This case may suggest a stereo
      selective analgesic effect of lidocaine accompanied by regional cerebral blood
      flow changes in the thalamus, indicating that sodium channels could, in fact, be
      highly expressed or modified in the thalamus after thalamic deafferentation.
      IMPLICATIONS: We present a case of persistent central pain after encephalitis in
      a patient who had long-term pain relief after a series of IV lidocaine infusions.
      A positron emission tomography scan study, done before and after treatment,
      suggested that lidocaine for the diagnosis of chronic neuropathic pain may have a
      specific site of action in the brain.

PMID- 15155311
TI  - Evaluation of the neuroprotective effects of S(+)-ketamine during open-heart
      surgery.
AB  - We compared the effect of S(+)-ketamine to remifentanil, both in combination with
      propofol, on the neurocognitive outcome after open-heart surgery in 106 patients.
      A battery of neurocognitive tests was administered before surgery and 1 and 10 wk
      after surgery. Fourteen patients (25%) in the control group and 10 patients (20%)
      in the S(+)-ketamine group had 2 or more tests with a cognitive deficit (decline
      by at least one preoperative SD of that test in all patients) 10 wk after surgery
      (P = 0.54). Z-scores were calculated for all tests. No significantly better
      performance could be detected in the S(+)-ketamine group, except for the
      Trailmaking B test 10 wk after surgery. We conclude that S(+)-ketamine offers no
      greater neuroprotection compared with remifentanil during open-heart surgery.
      IMPLICATIONS: N-methyl-D-aspartic acid receptors play an important role during
      ischemic brain injury. We could not demonstrate that S(+)-ketamine resulted in
      greater neuroprotective effects compared with remifentanil during cardiopulmonary
      bypass procedures when both were combined with propofol.

PMID- 15155310
TI  - The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary
      function and the release of inflammatory mediators.
AB  - Reduction of the inflammatory reaction with the use of heparin coating has been
      found during and after cardiopulmonary bypass (CPB). The question remains whether
      this reduced reaction also decreases the magnitude of CPB-induced pulmonary
      dysfunction. We therefore evaluated the effects of a heparin-coated circuit
      versus a similar uncoated circuit on pulmonary indices as well as on inflammatory
      markers of complement activation (C3b/c), elastase-alpha(1)-antitrypsin complex,
      and secretory phospholipase A(2) (sPLA(2)) during and after CPB. Fifty-one
      patients were randomly assigned into two groups undergoing coronary artery bypass
      grafting with either a heparin-coated (Group 1) or an uncoated (Group 2) circuit.
      During CPB, a continuous positive airway pressure of 5 cm H(2)O and a fraction of
      inspired oxygen (FIO(2)) of 0.21 were maintained. Differences in favor of the
      coated circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary
      vascular resistance index (P < 0.05), and PaO(2)/FIO(2) ratio (P < 0.05) after
      CPB and in the intensive care unit. During and after CPB, the coated group
      demonstrated lower levels of sPLA(2). After CPB, C3b/c and the elastase-alpha(1)
      antitrypsin complex were significantly less in the coated group (P < 0.001). The
      coated circuit was associated with a reduced inflammatory response, decreased
      pulmonary vascular resistance index and pulmonary shunt fraction, and increased
      PaO(2)/FIO(2) ratio, suggesting that the coated circuit may have beneficial
      effects on pulmonary function. The correlation with sPLA(2), leukocyte
      activation, and postoperative leukocyte count suggests reduced activation of
      pulmonary capillary endothelial cells. IMPLICATIONS: Heparin coating of the
      extracorporeal circuit reduces the inflammatory response during cardiopulmonary
      bypass. Analysis of indices of pulmonary function indicates that use of heparin
      coating may result in less impaired gas exchange.

PMID- 15155312
TI  - Lung recruitment improves the efficiency of ventilation and gas exchange during
      one-lung ventilation anesthesia.
AB  - Atelectasis in the dependent lung during one-lung ventilation (OLV) impairs
      arterial oxygenation and increases dead space. We studied the effect of an
      alveolar recruitment strategy (ARS) on gas exchange and lung efficiency during
      OLV by using the single-breath test of CO(2) (SBT-CO(2)). Twelve patients
      undergoing thoracic surgery were studied at three points in time: (a) during two
      lung ventilation and (b) during OLV before and (c) after an ARS. The ARS was
      applied selectively to the dependent lung and consisted of an increase in peak
      inspiratory pressure up to 40 cm H(2)O combined with a peak end-expiratory
      pressure level of 20 cm H(2)O for 10 consecutive breaths. The ARS took
      approximately 3 min. Arterial blood gases, SBT-CO(2), and metabolic and
      hemodynamic variables were recorded at the end of each study period. Arterial
      oxygenation and dead space were better during two-lung ventilation compared with
      OLV. PaO(2) increased during OLV after lung recruitment (244 +/- 89 mm Hg) when
      compared with OLV without recruitment (144 +/- 73 mm Hg; P < 0.001). The SBT
      CO(2) analysis showed a significant decrease in dead-space variables and an
      increase in the variables related to the efficiency of ventilation during OLV
      after an ARS when compared with OLV alone. In conclusion, ARS improves gas
      exchange and ventilation efficiency during OLV. IMPLICATIONS: In this article, we
      showed how a pulmonary ventilatory maneuver performed in the dependent lung
      during one-lung ventilation anesthesia improved arterial oxygenation and dead
      space.

PMID- 15155313
TI  - Adverse gastrointestinal complications after cardiopulmonary bypass: can outcome
      be predicted from preoperative risk factors?
AB  - Adverse gastrointestinal (GI) outcome after cardiac surgery is an infrequent
      event but is a clinically important health care problem because of associated
      increased morbidity and mortality. The ability to identify patients at greatest
      risk before surgery may be helpful in planning appropriate perioperative
      management strategies. We examined the pre- and intraoperative characteristics of
      2417 patients from 24 diverse United States medical centers enrolled in the
      Multicenter Study of Perioperative Ischemia Study who were undergoing cardiac
      surgery using cardiopulmonary bypass as predictors for adverse GI outcome.
      Resource utilization was evaluated for patients with and without adverse GI
      outcomes. Adverse GI outcomes occurred in 5.5% of patients (133 of 2417),
      increased in-hospital mortality 6.5-fold, prolonged the mean intensive care unit
      length of stay by 1 wk, and more than doubled the mean postoperative hospital
      stay (P < 0.0001). Predictors of adverse GI outcome included decreased left
      ventricular function, hyperbilirubinemia, thrombocytopenia, prolonged partial
      thromboplastin time, prior cardiovascular surgery, combined coronary artery
      bypass graft surgery and intracardiac or proximal aortic surgery, pharmacological
      cardiovascular support, and intraoperative transfusion. The literature suggests
      that adverse GI outcome after cardiac surgery is secondary to poor splanchnic
      perfusion, which many of these risk factors may predict. Therefore, patients
      deemed to be at risk before surgery may benefit from tightly controlled
      hemodynamic management and other strategies that optimize perioperative organ
      perfusion. IMPLICATIONS: We identified the preoperative and intraoperative
      predictors associated with an increased incidence of postoperative
      gastrointestinal complications after cardiac surgery using cardiopulmonary
      bypass. Because these complications are associated with frequent morbidity and
      mortality, these predictors may be helpful in identifying patients at increased
      risk so that risk stratification can be modified and perioperative management can
      be appropriately adjusted.

PMID- 15155314
TI  - Enhanced vasodilatory responses to milrinone in catecholamine-precontracted small
      pulmonary arteries.
AB  - Beta-adrenergic agonists (e.g., epinephrine [E] and norepinephrine [NE]) and
      phosphodiesterase-III inhibitors (e.g., milrinone) are often used in combination
      to augment ventricular function in the perioperative period. In the myocardium,
      milrinone acts synergistically with beta-adrenergic agonists to increase
      contractility. However, the potential interaction between catecholamines with
      combined alpha- and beta-adrenergic activity and milrinone in the pulmonary
      circulation has not been determined. We evaluated the vasodilatory effects of
      milrinone and nitroglycerine on large elastic and small muscular porcine
      pulmonary vascular rings precontracted with catecholamines with beta-adrenergic
      agonist activity (E and NE), the alpha-adrenergic agonist phenylephrine, and a
      nonadrenergic agonist, the thromboxane analog U46619. In small pulmonary
      arteries, the vasorelaxation with milrinone was significantly enhanced in rings
      precontracted with E or NE compared with those precontracted with phenylephrine
      or U46619. However, in large pulmonary arteries, the vasorelaxation with
      milrinone was similar in all vessel rings and was not influenced by the agonist
      used to induce precontraction. In marked contrast, the vasorelaxant responses to
      nitroglycerine were not altered by the specific agonist used for precontraction
      in either small or large pulmonary vascular rings. Thus, the pulmonary vascular
      effects of milrinone are enhanced when combined with drugs with beta
      adrenoreceptor agonist activity. The vasodilatory interactions exhibited by
      phosphodiesterase-III inhibitors and the catecholamines NE and E suggest that
      their combined use might be beneficial in circumstances in which ventricular
      dysfunction and increased pulmonary vascular resistance occur. IMPLICATIONS: This
      study demonstrated that milrinone had enhanced vasodilator effects when combined
      with drugs with beta-adrenoreceptor agonist activity in small pulmonary artery
      segments removed from pigs.

PMID- 15155315
TI  - Factor V Leiden and perioperative risk.
AB  - Factor V Leiden (FVL) is the most common known inherited cause of thrombophilia;
      it is present in approximately 5% of the Caucasian population. Although the risk
      of venous thrombosis associated with this polymorphism in various medical
      settings is well described, its effect on perioperative risk is only beginning to
      be explored. Specifically, there are few studies addressing the potential risks
      of FVL in the surgical population, in which both hemorrhagic and thrombotic
      complications convey substantial clinical and economic significance. There are
      speculations and unproven hypotheses regarding FVL in this population, and these
      therefore highlight the need to comprehensively address this issue. This review
      will describe the physiology of the FVL mutation, briefly clarify its risk in the
      nonsurgical setting, and assess current data regarding FVL in noncardiac and
      cardiac surgery. Finally, a summary of current clinical evidence and a plan for
      more detailed investigation of this potentially significant risk factor will be
      proposed.

PMID- 15155316
TI  - Reversal of direct thrombin inhibition after cardiopulmonary bypass in a patient
      with heparin-induced thrombocytopenia.
AB  - We treated persistent hemorrhage after cardiopulmonary bypass in a heart
      transplant recipient who had received anticoagulation with the direct thrombin
      inhibitor bivalirudin by a combination therapy aimed at reducing the plasma
      concentration of the thrombin antagonist (hemodialysis and modified
      ultrafiltration), increasing the concentration of thrombin at bleeding sites
      (recombinant factor VIIa), and increasing the plasma concentration of other
      coagulation factors (fresh frozen plasma and cryoprecipitate). The bleeding was
      controlled, and there was no thrombotic complication. IMPLICATIONS: A combination
      of modified ultrafiltration, hemodialysis, and the administration of recombinant
      factor VIIa, fresh frozen plasma, and cryoprecipitate may reverse the
      anticoagulant effect of bivalirudin.

PMID- 15155317
TI  - Use of continuous paravertebral analgesia to facilitate neurologic assessment and
      enhance recovery after thoracoabdominal aortic aneurysm repair.
AB  - Neurologic assessment after thoracic aortic aneurysm repair is important for
      detecting and treating late onset paraplegia. Traditional methods of pain
      control, such as patient-controlled IV analgesia and epidural analgesia, may
      interfere with neurologic assessment. We present a case of a patient who received
      continuous thoracic paravertebral analgesia that provided excellent analgesia
      while preserving the ability to monitor neurologic function. IMPLICATIONS: We
      provided postoperative continuous paravertebral analgesia in a patient after
      thoracoabdominal aneurysm repair requiring postoperative neurologic assessment.
      Paravertebral analgesia provides unilateral analgesia with fewer neurologic and
      hemodynamic side effects than central neuraxial blockade and should be considered
      for management of patients undergoing thoracic aortic aneurysm repair.

PMID- 15155318
TI  - Bispectral index during isoflurane anesthesia in pediatric patients.
AB  - Bispectral index (BIS) was developed to monitor anesthetic depth in adults, but
      has been investigated for use in children, using sevoflurane. We examined the
      concentration-response relationship between BIS and isoflurane. Thirty children
      undergoing cardiac catheterization received continuous intraoperative BIS
      monitoring and had BIS values recorded at 6 steady-state end-tidal isoflurane
      (Et(Iso)) concentrations between 1.5% and 0.5% and at first arousal. The mean
      (SD) values for BIS were as follows: 1.5%, 32.3 +/- 11.7; 1.3%, 34.7 +/- 12.5;
      1.1%, 40.5 +/- 13.3; 0.9%, 48.0 +/- 13.7; 0.7%, 55.9 +/- 14.4; and 0.5%, 61.8 +/-
      13.1. There was an inverse correlation between Et(Iso) and BIS (r = -0.634; P <
      0.01). There were significant differences (P < 0.0001) in mean BIS values between
      adjacent Et(Iso) in all cases except 1.5% versus 1.3%. An inhibitory sigmoid
      E(max) model best described the BIS-isoflurane concentration relationship, with
      an 50% effective dose of 0.85% (95% confidence interval, 0.72%-0.98%). The mean
      value of BIS at first arousal was 78.5 +/- 12.3. The relationship between Et(Iso)
      and BIS is qualitatively and quantitatively similar to that described for
      isoflurane in adults and sevoflurane in children. These results add to the body
      of evidence that BIS is adequately calibrated for use in children older than 1
      yr. IMPLICATIONS: This observational study of children undergoing cardiac
      catheterization characterizes the concentration-response relationship between
      bispectral index and isoflurane and demonstrates that bispectral index seems
      adequately calibrated for monitoring the depth of isoflurane anesthesia in
      pediatric patients.

PMID- 15155319
TI  - Heparinase-modified thrombelastography in term and preterm neonates.
AB  - Thrombelastography (TEG) appears to be a promising test to assess coagulation in
      infants and children. TEG enables a rapid assessment of hemostatic function with
      only 300 microL of whole blood and provides information about plasmatic
      coagulation, platelet function, and fibrinolysis. In this study, we used TEG to
      assess the coagulation system of preterm and term neonates to determine the
      effects of their deficient coagulation factor levels on global hemostatic
      function. Heparinase-modified TEG, platelet and red blood cell count, plasma
      fibrinogen, and prothrombin time were assessed in four groups of clinically
      stable infants: severely preterm (gestational age [GA], 27-31 wk), moderately
      preterm (GA, 32-36 wk), term (GA, 36-40 wk), and former preterm (corrected GA, 34
      40 wk). Healthy adult volunteers served as a control group. When compared with
      the adult group, thromboelastography revealed no defects in coagulation from
      groups of clinically stable infants, documenting the functional integrity of
      coagulation despite, in part, decreased conventional coagulation variables.
      Because clinically stable preterm and term infants show a relatively small
      incidence of bleeding, despite prolonged conventional coagulation tests, TEG may
      better reflect the hemostatic potential of these patients compared with
      conventional coagulation tests. IMPLICATIONS: This study assessed the coagulation
      of preterm and term infants by thrombelastography and found functional integrity
      of coagulation despite, in part, decreased conventional coagulation variables.

PMID- 15155320
TI  - Perioperative pain management of a complex orthopedic surgical procedure with
      double continuous nerve blocks in a burned child.
AB  - The use of catheters for continuous nerve blocks has been established in
      children, although in most series only one catheter was used. We report a case of
      a 3-yr-old child who underwent a toe-to-finger transfer managed with 2 regional
      catheters: axillary and sciatic. A pain score of 0 was noted during the entire
      study period. The total dose of bupivacaine was limited to an acceptable range,
      and the child recovered completely. This report adds to growing evidence in favor
      of the safety and efficacy of continuous peripheral nerve blocks in pediatric
      patients. IMPLICATIONS: Double continuous nerve blocks allow optimal analgesia in
      burned children after complex orthopedic surgery without major adverse events.
      Plasma concentrations of bupivacaine remained small during the study period.

PMID- 15155321
TI  - Superficial cervical plexus block for vocal cord surgery in an awake pediatric
      patient.
AB  - Medialization thyroplasty is a surgical procedure that decreases the incidence of
      dysphonia and dysphagia in patients who have vocal cord paralysis. We report a
      case of a pediatric patient who underwent this procedure with minimal sedation
      and bilateral superficial cervical plexus blockade. The use of a regional
      technique provided analgesia while allowing the patient to phonate at the request
      of the surgeon. IMPLICATIONS: Medialization thyroplasty is a surgical procedure
      that decreases the incidence of dysphagia and dysphonia in patients with vocal
      cord paralysis. This procedure is best performed in a patient who maintains the
      ability to phonate. We report a case of medialization thyroplasty in a pediatric
      patient after bilateral superficial cervical plexus blocks with minimal sedation.

PMID- 15155322
TI  - The use of dexmedetomidine to facilitate opioid and benzodiazepine detoxification
      in an infant.
AB  - Prolonged use of opioids and benzodiazepines for the care of critically ill
      infants and children can generate physical dependence. We present a case of an 8
      mo-old infant with Hunter's syndrome who was maintained on very large doses of
      fentanyl and midazolam and who could not be weaned from these drugs by
      conventional taper. We used dexmedetomidine, an alpha(2)-adrenergic agonist, to
      facilitate opioid and benzodiazepine withdrawal. A processed electroencephalogram
      (Bispectral Index) was used to guide the titration of dexmedetomidine in this
      neurologically impaired infant. This is the first report of this drug being used
      in an infant to manage chemical dependence withdrawal. IMPLICATIONS:
      Dexmedetomidine was used to facilitate opioid and benzodiazepine withdrawal in an
      8-mo-old infant. A processed electroencephalogram (Bispectral Index) was used to
      guide the titration of dexmedetomidine in this neurologically impaired infant.
      This is the first report of dexmedetomidine use in an infant to manage chemical
      dependence withdrawal.

PMID- 15155323
TI  - Prophylaxis of postoperative nausea and vomiting with oral, long-acting
      dimenhydrinate in gynecologic outpatient laparoscopy.
AB  - Dimenhydrinate is an inexpensive antiemetic with few side effects available as an
      oral, long-acting (LA) formulation (Gravol L/A) containing 25 mg of immediate and
      50 mg of sustained release drug. We designed this double-blind comparison trial
      to assess the efficacy of dimenhydrinate LA versus droperidol alone and the
      combination for prophylaxis of nausea, vomiting, and retching in outpatient
      gynecologic laparoscopy. One-hundred-forty-one women were randomized into 3
      groups: 1) droperidol (placebo capsule preoperatively and IV droperidol 0.625 mg
      before induction), 2) dimenhydrinate LA preoperatively and IV placebo before
      induction, or 3) combination. Information regarding nausea, vomiting, retching,
      pain, and sedation was recorded in the postanesthesia care unit (PACU) and
      collected by telephone for the presence of symptoms: on arrival home; at bedtime;
      upon arising, and at lunchtime the following day. The overall incidence of
      complete treatment failure (rescue medication in PACU or nausea, vomiting, or
      retching at any time point) was 28 of 46 (61%), 28 of 48 (58%), and 22 of 47
      (47%); and for treatment failure vomiting (rescue medication in PACU or vomiting
      or retching at any time point) was 16 of 46 (35%), 11 of 48 (23%), and 5 of 47
      (11%), for the droperidol, dimenhydrinate, and combination groups, respectively
      (P = 0.007 for droperidol versus combination). There were no differences in
      sedation or pain. Preoperative administration of an oral dose of LA
      dimenhydrinate in combination with droperidol when compared with droperidol alone
      effectively reduced the incidence of vomiting but not nausea in women undergoing
      elective outpatient gynecologic laparoscopy. IMPLICATIONS: Dimenhydrinate is an
      inexpensive antiemetic with few side effects available as a long-acting oral
      formulation. Women undergoing outpatient gynecologic laparoscopy were given
      droperidol, an effective antiemetic, dimenhydrinate alone, or the combination of
      the two drugs. Dimenhydrinate plus droperidol significantly reduced the overall
      incidence of vomiting, but not nausea, when compared with droperidol alone.

PMID- 15155324
TI  - Preoperative parenteral parecoxib and follow-up oral valdecoxib reduce length of
      stay and improve quality of patient recovery after laparoscopic cholecystectomy
      surgery.
AB  - In this randomized, double-blinded, placebo-controlled study, we evaluated the
      effects of preoperative IV parecoxib sodium (parecoxib) followed by postoperative
      oral valdecoxib on length of stay, resource utilization, opioid-related side
      effects, and patient recovery after elective laparoscopic cholecystectomy.
      Patients were randomized to receive a single IV dose of parecoxib 40 mg (n = 134)
      or placebo (n = 129) 30-45 min before the induction of anesthesia. Six to 12 h
      after the IV dose, the parecoxib group received a single oral dose of valdecoxib
      40 mg, followed by valdecoxib 40 mg once daily on postoperative Days 1-4 and then
      40 mg once daily as needed on Days 5-7. Patients in the parecoxib/valdecoxib
      group had a shorter length of stay in the postanesthesia care unit (78 +/- 47
      min) compared with those taking placebo (90 +/- 49 min; P < 0.05). Patients in
      the parecoxib/valdecoxib group also had reduced pain intensity and, after
      discharge, experienced a significant reduction in vomiting in the first 24 h,
      slept better, returned to normal activity earlier, and expressed greater
      satisfaction than placebo patients (P < 0.05). Preoperative parecoxib followed by
      postoperative valdecoxib is a valuable adjunct for treating pain and improving
      patient outcome after laparoscopic cholecystectomy. IMPLICATIONS: The
      administration of preoperative IV parecoxib followed by oral valdecoxib after
      surgery resulted in a shorter length of stay in the postoperative anesthesia care
      unit, a better quality of postoperative recovery, and a faster return to normal
      activity, with greater patient satisfaction, after laparoscopic cholecystectomy.

PMID- 15155326
TI  - Will succinylcholine ever disappear?

PMID- 15155327
TI  - Muscular injury after succinylcholine and electroconvulsive therapy.
AB  - Both succinylcholine and seizures cause muscular injury during electroconvulsive
      therapy. We compared the muscular damage in two groups of patients. The
      psychiatric patient group received succinylcholine for electroconvulsive therapy.
      The surgical patient group received succinylcholine for endotracheal intubation.
      Serum myoglobin was measured as a marker for muscular injury and myalgic symptoms
      were also recorded. Serum myoglobin increased from baseline in both groups at 5
      and 20 min. The surgical patients, however, had a higher myoglobin level than the
      psychiatric patients at 5 and 20 min after the administration of succinylcholine
      (P < 0.001). The median (range) of myoglobin concentration at 20 min in
      psychiatric patients was 32.6 (23.1-60.1) ng/mL, compared with 61.2 (31.6-1687.0)
      ng/mL in surgical patients. The incidence of myalgia was not different between
      the two groups. In conclusion, we unexpectedly conclude that the psychiatric
      patients who received electroconvulsive therapy had less effect of muscular
      damage associated with succinylcholine than the surgical patients did.
      IMPLICATIONS: Both succinylcholine and electroconvulsive therapy cause muscular
      injury. However, we unexpectedly found that psychiatric patients who received
      succinylcholine and electroconvulsive therapy had less muscular damage than
      surgical patients who received succinylcholine for intubation. Therefore,
      appropriate use of succinylcholine can attenuate the muscular damaging effect
      from the therapy.

PMID- 15155328
TI  - The neuromuscular effects and tracheal intubation conditions after small doses of
      succinylcholine.
AB  - Succinylcholine 1.0 mg/kg usually produces excellent tracheal intubation
      conditions in 60 s. Recovery of respiratory muscle function after this dose,
      however, is not fast enough to forestall oxyhemoglobin desaturation when
      ventilation cannot be assisted. In this study, we investigated whether smaller
      doses of succinylcholine can produce satisfactory intubation conditions fast
      enough to allow rapid sequence induction with a shorter recovery time. Anesthesia
      was induced with fentanyl/propofol and maintained by propofol infusion and N(2)O
      in O(2). After the induction, 115 patients were randomly allocated to five groups
      according to the dose of succinylcholine (0.3 mg/kg, 0.4 mg/kg, 0.5 mg/kg, 0.6
      mg/kg, or 1.0 mg/kg). Evoked adductor pollicis responses to continuous 1-Hz
      supramaximal ulnar nerve stimulation were recorded using acceleromyography.
      Tracheal intubation conditions were graded 60 s after succinylcholine
      administration. Onset time, maximal twitch depression, time to initial twitch
      detection after paralysis, and to 10%, 25%, 50%, and 90% twitch height recovery
      were recorded. Time to initial diaphragmatic movement as well as time to
      resumption of regular spontaneous respiratory movements were calculated. Onset
      times ranged between 82 s and 52 s, decreasing with increasing doses of
      succinylcholine but not differing between 0.6 and 1 mg/kg. Maximum twitch
      depression was similar after 0.5, 0.6, and 1 mg/kg (98.2%-100%). Recoveries of
      twitch height and apnea time were dose-dependent. Intubation conditions were
      often unacceptable after 0.3- and 0.4-mg/kg doses. Acceptable intubation
      conditions were achieved in all patients receiving a 0.5, 0.6, and 1 mg/kg dose
      of succinylcholine. Intubation conditions in patients receiving 0.6 and 1 mg/kg
      were identical, whereas times to T(1) = 50% and 90% and time to regular
      spontaneous reservoir bag movements were significantly shorter in the 0.6-mg/kg
      dose group (5.78, 7.25, and 4.0 min, respectively) versus patients receiving 1
      mg/kg (8.55, 10.54, and 6.16 min, respectively). The use of 0.5 to 0.6 mg/kg of
      succinylcholine can produce acceptable intubation conditions 60 s after
      administration. The conditions achieved after 0.6 mg/kg are similar to those
      after 1.0 mg/kg. These smaller doses are associated with faster twitch recovery
      and shorter apnea time. IMPLICATIONS: In normal healthy patients, succinylcholine
      0.6 mg/kg produces clinical intubation conditions identical to the traditional
      1.0-mg/kg dose but is associated with a shorter recovery time.

PMID- 15155329
TI  - Posttetanic potentiation and fade in the response to tetanic and train-of-four
      stimulation during succinylcholine-induced block.
AB  - We designed this study to confirm anecdotal observations that neuromuscular block
      after a single administration of succinylcholine is characterized by fade to
      train-of-four (TOF) or tetanic stimulation, as well as posttetanic potentiation.
      This prospective, randomized, 2-center observational study involved 100 patients.
      Patients were allocated to 1 of 5 groups and received 0.1, 0.3, 0.5, 0.75, or 1.0
      mg/kg succinylcholine during propofol/fentanyl/nitrous oxide anesthesia.
      Neuromuscular function was monitored by TOF using mechanomyography. At 10%-20%
      spontaneous recovery of the first twitch of TOF, the mode of stimulation was
      changed from TOF to 1-Hz single-twitch stimulation followed by a tetanic stimulus
      (50 Hz) for 5 s. Three seconds later, the single twitch (1 Hz) was applied again
      for approximately 30 s followed by TOF stimulation until full recovery of the TOF
      response. Succinylcholine-induced neuromuscular block had the following
      characteristics: 1) twitch augmentation before twitch depression, which was seen
      more frequently in patients given smaller doses (0.1 and 0.3 mg/kg) than in those
      given larger doses (0.5-1.0 mg/kg); 2) TOF fade during onset and recovery of the
      block; 3) tetanic fade; and 4) and posttetanic potentiation. Posttetanic
      potentiation was related to the pretetanic twitch height but was not related to
      the dose of succinylcholine administered. Some characteristics of Phase II block
      were detectable during onset and recovery from doses of succinylcholine as small
      as 0.30 mg/kg. Posttetanic potentiation and fade in response to train-of-four and
      tetanic stimuli are characteristics of neuromuscular block after bolus
      administration of different doses of succinylcholine. IMPLICATIONS: Posttetanic
      potentiation and fade in response to train-of-four and tetanic stimuli are
      characteristics of neuromuscular block after bolus administration of different
      doses of succinylcholine. We also conclude that some characteristics of a Phase
      II block are evident from an initial dose (i.e., as small as 0.3 mg/kg) of
      succinylcholine.

PMID- 15155330
TI  - Methadone for the induction of anesthesia: plasma histamine concentration,
      arterial blood pressure, and heart rate.
AB  - Despite the widespread use of methadone for the treatment of acute and chronic
      pain, the hemodynamic effects of methadone administered by IV bolus have not been
      studied. We compared the hemodynamic effects of an IV bolus of methadone 20 mg
      with those of fentanyl 10 microg/kg for the induction of anesthesia in
      combination with etomidate 0.3 mg/kg. Forty-three patients undergoing major
      surgery were randomized to one of the two treatments in a double-blinded fashion.
      Plasma concentrations of histamine were measured before and 2 min after opioid
      administration. Heart rate and arterial blood pressure were measured via an
      arterial line just before opioid administration, etomidate administration, and
      tracheal intubation; during intubation; and 1 min after intubation. There were no
      significant differences in mean heart rate between the methadone and fentanyl
      groups at any time point. Systolic and diastolic blood pressures were
      significantly lower (P < 0.05) in the fentanyl group just before intubation,
      during intubation, and 1 min after intubation. Mean plasma concentrations of
      histamine before and after the administration of methadone or fentanyl were 1.54
      ng/mL (SD, 0.65 ng/mL) and 1.57 ng/mL (SD, 1.37 ng/mL) or 1.00 ng/mL (SD, 0.58
      ng/mL) and 1.04 ng/mL (SD, 0.47 ng/mL), respectively. Despite the lack of a
      significant change in mean plasma concentrations of histamine, substantial
      increases in plasma histamine occurred in 2 of 23 patients who received
      methadone. There were no obvious hemodynamic effects associated with histamine
      concentrations up to 6.2 ng/mL. Methadone appears to have the potential for
      producing histamine release. Although methadone administration did not produce
      hemodynamic instability in this study, the possible hemodynamic side effects of
      histamine release should be considered when IV boluses of methadone are given.
      IMPLICATIONS: The same dose of IV methadone (20 mg) that is effective for
      postoperative pain is also suitable for the induction of anesthesia in
      combination with etomidate. The plasma histamine concentration was notably
      increased in two patients, without obvious hemodynamic sequelae. Therefore,
      methadone appears to have the potential for producing histamine release.

PMID- 15155332
TI  - A specific alteration in the electroretinogram of Drosophila melanogaster is
      induced by halothane and other volatile general anesthetics.
AB  - In higher organisms, physiological investigations have provided a valuable
      complement to assays of anesthetic effects on whole-animal behavior. However,
      although complex motor programs of Drosophila melanogaster have been used to
      identify genes that influence anesthesia, electrophysiological studies of
      anesthetic effects in this invertebrate have been limited. Here we show that the
      electroretinogram (ERG), the extracellular recording of light-evoked mass
      potentials from the surface of the eye, reveals a distinct effect of halothane,
      enflurane, isoflurane, and desflurane. Behaviorally relevant concentrations of
      these volatile anesthetics severely reduced the transient component of the ERG at
      lights-off. Other prominent ERG components, such as the photoreceptor potential
      and the lights-on transient, were not consistently affected by these drugs.
      Surprisingly, for most anesthetics, a diminished off-transient was obtained only
      with short light pulses. An identical effect was observed in the absence of
      anesthetic by depressing the function of Shaker potassium channels. The
      possibility that halothane acts in the visual circuit by closing potassium
      channels was examined with a simple genetic test; the results were consistent
      with the hypothesis but fell short of providing definitive support. Nevertheless,
      our studies establish the ERG as a useful tool both for examining the influence
      of volatile anesthetics on a simple circuit and for identifying genes that
      contribute to anesthetic sensitivity. IMPLICATIONS: Electroretinography (ERG)
      provides a useful monitor of anesthetic effects on the fruit fly. The effects of
      volatile anesthetics on the ERG are recapitulated by inactivation of potassium
      channels.

PMID- 15155331
TI  - Morphine-induced analgesia, hypotension, and bradycardia are enhanced in
      hypertensive rats.
AB  - Several studies have emphasized an opioidergic link between the central
      regulation of cardiovascular function and acute noninflammatory pain. By
      contrast, relatively few studies have investigated the relationships between
      opioids, hypertension, and inflammatory pain. We used the formalin model of acute
      inflammatory pain to compare morphine antinociception among spontaneously
      hypertensive (SHR) rats, their genetic normotensive controls, Wistar-Kyoto (WKY)
      rats, and Sprague-Dawley (SD) rats. Measures of nociception included both
      behavioral and cardiovascular end-points (increased mean arterial blood pressure
      and heart rate). Morphine (3.0 mg/kg subcutaneously) produced greater hypotension
      and bradycardia in SHR than in WKY or SD rats. We next administered formalin (5%;
      50 microL) and observed greater nociception during both Phase 1 and Phase 2 in
      SHR controls than in WKY controls. The morphine-treated groups did not differ,
      suggesting that morphine attenuates hypersensitivity to formalin pain in the SHR.
      Morphine inhibited edema but not paw hyperthermia to a greater degree in SHR,
      whereas Phase 1 remifentanil produced a relatively shorter delay in the onset of
      Phase 2 in SHR. We suggest that the presentation of essential hypertension be
      considered when opioid regimens are planned both during surgery (to minimize
      cardiovascular complications) and during the postoperative period (to optimize
      analgesic effects). IMPLICATIONS: Presentation of essential hypertension should
      be considered when opioid regimens are planned both during surgery (to minimize
      cardiovascular complications) and during the postoperative period (to optimize
      analgesic effects).

PMID- 15155333
TI  - Insulin decreases isoflurane minimum alveolar anesthetic concentration in rats
      independently of an effect on the spinal cord.
AB  - The observation that insulin supplies an element of analgesia suggests that
      insulin administration might decrease the concentration of inhaled anesthetic
      required to produce MAC (the minimum alveolar anesthetic concentration required
      to eliminate movement in response to noxious stimulation in 50% of subjects). We
      hypothesized that insulin decreases MAC by directly affecting the nervous system,
      by decreasing blood glucose, or both. To test these hypotheses, we infused
      increasing doses of insulin either intrathecally or IV in rats anesthetized with
      isoflurane and determined the resulting MAC change (assessing forelimb and
      hindlimb movement separately). Infusion of insulin produced a dose-related
      decrease in MAC that did not differ among groups. That is, the IV and intrathecal
      infusions caused similar decreases in MAC at a given infusion rate. Blood glucose
      concentrations were larger in the rats given insulin with 5% dextrose. However,
      the percentage change in MAC determined from forelimb versus hindlimb movement
      did not differ. For a given insulin infusion rate, MAC changes and glucose levels
      did not correlate with each other, except, possibly, for the most rapid infusion
      rate, for which smaller glucose concentrations were associated with a marginally
      larger decrease in MAC. Intrathecal infusions of insulin did not produce spinal
      cord injury. In summary, we found that insulin decreases isoflurane MAC in a dose
      related manner independently of its effects on the blood concentration of
      glucose. The sites at which insulin acts to decrease MAC appear to be supraspinal
      rather than spinal. The effect may be due to a capacity of insulin to produce
      analgesia through an action on one or more neurotransmitter receptors.
      IMPLICATIONS: Intrathecal and IV insulin administration equally decrease
      isoflurane MAC in rats, regardless of the concentration of blood sugar. These
      findings indicate that although insulin decreases MAC, the decrease is not
      mediated by actions on the spinal cord.

PMID- 15155334
TI  - Isoflurane reduces glutamatergic transmission in neurons in the spinal cord
      superficial dorsal horn: evidence for a presynaptic site of an analgesic action.
AB  - The minimum alveolar concentration (MAC) of a volatile anesthetic defines
      anesthetic potency in terms of a suppressed motor response to a noxious stimulus.
      Therefore, the MAC of an anesthetic might in part reflect depression of motor
      neuron excitability. In the present study we evaluated the effect of isoflurane
      (ISO) on neurons in the substantia gelatinosa driven synaptically by putative
      nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell
      patch-clamp recordings were performed in neurons with their soma in the
      substantia gelatinosa of transverse rat spinal cord slices. We investigated the
      effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root
      stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO
      reversibly reduced the amplitude of eEPSC to 39% +/- 22% versus control. ISO
      decreased the frequency of sEPSC and mEPSC to 39% +/- 26% and 63% +/- 7%. Neither
      the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We
      conclude that ISO depresses glutamatergic synaptic transmission of putative
      nociceptive primary-afferent inputs, presumably by reducing the release of the
      excitatory transmitter. This effect may contribute to an antinociceptive action
      of volatile anesthetics at the spinal cord level. IMPLICATIONS: The present
      electrophysiological in vitro experiments provide evidence that the volatile
      anesthetic isoflurane reduces excitatory transmitter release at the first site of
      synaptic integration of nociceptive inputs, the spinal cord superficial dorsal
      horn. This effect may contribute to the anesthetic action of volatile anesthetics
      at the spinal cord level.

PMID- 15155335
TI  - The effect of propofol on cytotoxicity and apoptosis of lipopolysaccharide
      treated mononuclear cells and lymphocytes.
AB  - IV anesthetics may inhibit proper immune responses and further compromise an
      already depressed defense system. To assess the possible role of propofol on
      human immune function in sepsis, we studied cytotoxicity, and apoptosis of
      mononuclear cells (MNCs). Peripheral blood MNCs were preincubated in 1 microg/mL
      of lipopolysaccharide (LPS) and then reincubated in different concentrations of
      propofol (1 microg/mL, 5 microg/mL, 10 microg/mL, or 50 microg/mL). To determine
      cytotoxicity, lactate dehydrogenase release was assayed by mixing MNCs (4 x
      10(5)/100 microL) with K-562 tumor cells as target cells (1 x 10(4)/100
      microL)(E: T ratio of 40:1). Apoptosis was determined by measuring the annexin
      positive cells using flow cytometry. Cytotoxicity and apoptosis of LPS-treated
      MNCs were unchanged by clinically acceptable concentrations of propofol (1
      microg/mL, 5 microg/mL, and 10 microg/mL). However, significant differences were
      observed in cytotoxicity (P = 0.004) and apoptosis (P = 0.002) with propofol 50
      microg/mL. By gating MNCs, we found that lymphocyte apoptosis was significantly
      increased at 50 microg/mL of propofol, but monocytes were unaffected (P = 0.02).
      In terms of cytotoxicity and apoptosis, propofol allowed MNCs to retain their
      cytotoxicity in septic conditions by protecting immune cells from apoptosis.
      IMPLICATIONS: Propofol at acceptable therapeutic concentrations, and under
      experimentally contrived septic conditions, did not affect the cytotoxic activity
      of mononuclear cells or the apoptosis level of mononuclear cells, lymphocytes,
      and monocytes from peripheral blood.

PMID- 15155336
TI  - Simultaneous determination of neuromuscular blockade at the adducting and
      abducting laryngeal muscles using phonomyography.
AB  - Phonomyography (PMG) is a new method for measuring neuromuscular blockade (NMB)
      at the larynx. In this study, we used PMG to compare NMB at the posterior
      cricoarytenoid (PCA) and the lateral cricoarytenoid muscle (LCA) in humans.
      Twelve patients were included in this study. Endotracheal intubation was
      performed without aid of neuromuscular blocking drugs. One small condenser
      microphone was inserted beside the vocal cords into the muscular process at the
      base of the arytenoid cartilage to record acoustic responses of the LCA (vocal
      cord adduction), and a second microphone was placed behind the larynx to measure
      NMB of the PCA (vocal cord abduction). Stimulation of the recurrent laryngeal
      nerve was performed using superficial electrodes placed at the neck (midline
      between jugular notch and cricoid cartilage) using train-of-four (TOF)
      stimulation every 12 s. After supramaximal stimulation, mivacurium 0.1 mg/kg was
      injected and onset, peak effect, and offset of NMB measured and compared using t
      test (P < 0.05). The data are presented as mean (SD). Peak effect, onset time,
      and early recovery to 25% of control twitch height were not significantly
      different between PCA and LCA at 86% (13) versus 78% (16), 2.3 min (0.45) versus
      2.3 min (1.0), and 9.55 min (3.05) versus 8.5 min (4.7), respectively. However,
      recovery to 75%, 90% of control twitch height, and recovery to a TOF ratio of 0.8
      were significantly longer at the PCA than at the LCA at 14 min (4) versus 11 min
      (5), 17 min (5) versus 11.8 min (5.6), and 17.5 min (5.6) versus 12.3 min (5.5),
      respectively. The authors conclude that recovery of NMB at the PCA takes longer
      than at the LCA in humans after mivacurium. IMPLICATIONS: After neuromuscular
      blockade in humans, the recovery of the ability to open the vocal cords takes
      longer than the ability to close the vocal cords.

PMID- 15155337
TI  - Change in bispectral index during epileptiform electrical activity under
      sevoflurane anesthesia in a patient with epilepsy.
AB  - We observed abnormal fluctuation in Bispectral Index (BIS) caused by repeated
      alternations between two electroencephalographic (EEG) waveform patterns in a
      patient with a recent history of epileptic seizure under sevoflurane anesthesia.
      The repetitive development of the abnormal EEG changes (slow delta with or
      without spike) and the fluctuation in BIS disappeared almost immediately after
      administration of anticonvulsants. BIS may give useful information not only on
      the sedative-hypnotic state, but also on the development of and recovery from
      abnormal epileptiform EEG activity. IMPLICATIONS: During epileptiform
      electroencephalographic activity (EEG), the Bispectral Index shows an abnormal
      fluctuation caused by repeated abrupt alterations between normal EEG and abnormal
      epileptiform EEG patterns.

PMID- 15155338
TI  - Increasing the value of time reduces the lost economic opportunity of caring for
      surgeries of longer-than-average times.
AB  - Anesthesiology groups that provide care for surgical procedures of longer-than
      average duration are economically disadvantaged by both increased staffing costs
      and reduced revenue. Under the current billing system, anesthesia time is valued
      the same regardless of the total case duration. In this study, we evaluated the
      effect on four academic anesthesiology departments of two hypothetical scenarios
      by changing the anesthesia care billing system to make more valuable either 1)
      all time units or 2) just second-hour and subsequent time units. From the four
      departments, case-specific data (anesthesia Current Procedural Terminology code
      and minutes of care) were collected for all anesthesia cases billed for 1 yr.
      Basic units were determined from the American Society of Anesthesiologists (ASA)
      relative value guide. The average time for each case was defined as the average
      anesthesia time for that specific Current Procedural Terminology code, as
      published by the Center for Medicare and Medicaid Services (CMS). The actual
      total ASA units per hour (tASA/h) was determined by adding all the basic units
      and time units and dividing by hours of anesthesia care (minutes of anesthesia
      care divided by 60). We then calculated a hypothetical CMS tASA/h for each group
      by substituting the CMS average time for each anesthesia procedure time for the
      actual time reported by each group and using 15-min time units. For each group,
      the Actual (Act) tASA/h and CMS tASA/h were calculated for both options-changing
      the interval for all time units or only for second and subsequent hours.
      Intervals were 15, 12, 10, 7, 6, or 5 min. When changing all time units, Act
      tASA/h and CMS tASA/h were never equal for all groups. The two productivity
      measures became approximately equal if only time units after the first hour were
      changed to 6- to 7-min intervals. When changes were applied only to the Act
      tASA/h (with CMS tASA/h remaining at 15-min intervals), at the 12-min interval
      either option resulted in a similar or higher Act tASA/h than CMS tASA/h. Both
      options increase the value of time and help compensate for the lost economic
      opportunity of longer-than-average surgical durations. IMPLICATIONS: Longer-than
      average surgical durations result in less potential revenue per hour under
      current billing methodology. This study quantifies the increase in billing
      productivity when the value of time is increased, when evaluating the billing
      productivity of four academic anesthesiology groups.

PMID- 15155339
TI  - Anesthesiologists should be familiar with the management of victims of terrorist
      attacks.

PMID- 15155340
TI  - Multiple casualty terror events: the anesthesiologist's perspective.
AB  - In a 28-mo period 14 multiple-casualty terror events occurred in Jerusalem,
      challenging the Department of Anesthesiology and Critical Care Medicine of the
      city's sole Level 1 trauma center. We performed a retrospective review of the
      response of the department to evaluate staff activities, resource use (emergency
      department, operating rooms, and intensive care unit [ICU]), and patient flow. A
      total of 1062 people were injured in the 14 multi-casualty terror incidents. The
      emergency department treated 355 victims; 108 of them were hospitalized, and 58
      underwent surgery during the first 8 h. Only two surgeries were performed during
      the first hour, and the average time to the first surgery was 124 min. Fifty-one
      patients were admitted to the ICU an average of 5.5 h after the terror event.
      After a terrorist act, multiple, simultaneous efforts were required of the
      anesthesiology department, including taking part in the initial resuscitation in
      the emergency department, anesthetizing victims for surgery and angiographies,
      and caring for them in the recovery room and ICU. Therefore, anesthesiology
      departments are greatly impacted by such events and must plan for them to
      maximize the use of available personnel and to have the appropriate equipment and
      supplies available. IMPLICATIONS: Anesthesiologists provide essential care to
      patients injured in terror events, from the initial resuscitation through
      therapeutic/diagnostic procedures and surgeries. Operational issues faced by a
      department of anesthesiology during the initial 8 h after terrorist actions were
      examined. Multiple, and often parallel, efforts were required of the department.

PMID- 15155341
TI  - Intraosseous vascular access in the treatment of chemical warfare casualties
      assessed by advanced simulation: proposed alteration of treatment protocol.
AB  - Current treatment protocols for chemical warfare casualties assume no IV access
      during the early treatment stages. Time constraints in mass casualty scenarios,
      impaired manual dexterity of medical personnel wearing protective gear, and
      victims' complex clinical presentations render standard IV access techniques
      impractical. A newly developed spring-driven, trigger-operated intraosseous
      infusion device may offer an effective solution. Sophisticated simulators were
      developed and used to mimic scenarios of chemical warfare casualties for
      assessing the feasibility of intraosseous infusion delivery. We evaluated the
      clinical performance of medical teams in full protective gear. The success rate
      in intraosseous insertion, time to completion of treatment goals, and outcome
      were measured in a simulated setting. Medical teams from major hospitals in
      Israel, designated for emergency response in a real chemical warfare mass
      casualty scenario, were trained in a simulated setting. All 94 participating
      physicians were supplied with conventional treatment modalities: only the 64
      study group physicians received intraosseous devices. The simulated survival rate
      was 73.4% for the study group and 3.3% for the controls (P < 0.001). Treatment
      goals were achieved within 3.5 min (range, 1-9 min) in the study group and within
      >10 min for controls (P < 0.001), and the complication rate for intraosseous use
      was 13.8%. Personnel satisfaction with the intraosseous device was unanimous and
      high. New-generation intraosseous infusions have great potential value in the
      early treatment stages of chemical warfare casualties. IMPLICATIONS: In a
      chemical warfare mass casualty scenario, the protective gear worn by medical
      personnel, the time constraints, and the casualties' medical condition impose
      limitations on the establishment of IV access during early treatment of the
      victims. A spring-driven, trigger-operated intraosseous infusion delivery system
      may offer an effective solution.

PMID- 15155342
TI  - Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of
      fluid resuscitation versus improved outcome after vasopressin.
AB  - In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of
      vasopressin versus an equal volume of saline placebo versus fluid resuscitation
      on hemodynamic variables and short-term survival. Twenty-one anesthetized pigs
      were subjected to severe liver injury. When mean arterial blood pressure was <20
      mm Hg and heart rate decreased, pigs randomly received either vasopressin IV (0.4
      U/kg; n = 7), an equal volume of saline placebo (n = 7), or fluid resuscitation
      (1000 mL each of lactated Ringer's solution and hetastarch; n = 7). Thirty
      minutes after intervention, surviving pigs were fluid resuscitated while bleeding
      was surgically controlled. Mean (+/- SEM) arterial blood pressure 5 min after the
      intervention was significantly (P < 0.05) higher after vasopressin than with
      saline placebo or fluid resuscitation (58 +/- 9 versus 7 +/- 3 versus 32 +/- 6 mm
      Hg, respectively). Vasopressin improved abdominal organ blood flow but did not
      cause further blood loss (vasopressin versus saline placebo versus fluid
      resuscitation 10 min after intervention, 1343 +/- 60 versus 1350 +/- 22 versus
      2536 +/- 93 mL, respectively; P < 0.01). Seven of 7 vasopressin pigs survived
      until bleeding was controlled and 60 min thereafter, whereas 7 of 7 saline
      placebo and 7 of 7 fluid resuscitation pigs died (P < 0.01). We conclude that
      vasopressin, but not saline placebo or fluid resuscitation, significantly
      improves short-term survival during uncontrolled hemorrhagic shock. IMPLICATIONS:
      Although IV fluid administration is the mainstay of nonsurgical management of
      trauma patients with uncontrolled hemorrhagic shock, the efficacy of this
      strategy has been discussed controversially. In this animal model of severe liver
      trauma with uncontrolled hemorrhagic shock, vasopressin, but not saline placebo
      or fluid resuscitation, improved short-term survival.

PMID- 15155343
TI  - A platelet activating factor receptor antagonist inhibits cytokine production in
      human whole blood by bacterial toxins and live bacteria.
AB  - We previously reported that a platelet-activating factor receptor (PAFR)
      antagonist (TCV-309) suppressed lipopolysaccharide (LPS)-induced mortality and
      tumor necrosis factor (TNF) production in mice. However, the effect of TCV-309 on
      cytokine production induced by Staphylococcus enterotoxin B (SEB) or live
      bacteria has not been reported. In this study we investigated the effect of TCV
      309 on cytokine production in human whole blood induced by LPS, SEB, and both
      Gram-positive and -negative bacteria. Human whole blood diluted 5:1 (980 microL)
      was placed in the wells of a 24-well plate. Ten microliters of LPS, SEB,
      Escherichia coli O18 K(+), or Staphylococcus aureus were added to each well.
      After incubation at 37 degrees C for 6 h, TNF, interleukin (IL)-6, and IL-8 in
      the culture medium were measured. TCV-309 did not affect the growth of either E.
      coli or S. aureus bacteria in the culture medium for the 6 h incubation. LPS,
      SEB, and both E. coli and S. aureus induced TNF, IL-6, and IL-8 in human whole
      blood. TCV-309 significantly inhibited the production of TNF, IL-6, and IL-8
      induced by LPS, SEB, and bacteria. A PAFR antagonist suppressed cytokine
      production induced by LPS, SEB, and both Gram-positive and -negative bacteria in
      human whole blood. A PAFR plays an important role of producing proinflammatory
      cytokines induced by both toxins and live bacteria. IMPLICATIONS: The platelet
      activating factor receptor plays an important role in producing proinflammatory
      cytokines induced by bacterial toxins, such as lipopolysaccharide,Staphylococcus
      enterotoxin B, and live Gram-positive and Gram-negative bacteria.

PMID- 15155344
TI  - A comparison of frontal and occipital bispectral index values obtained during
      neurosurgical procedures.
AB  - We placed bispectral index (BIS) sensors on the frontal and occipital areas of
      neurosurgical patients and compared BIS values obtained from both areas during
      propofol/fentanyl anesthesia. BIS showed a strong correlation between frontal and
      occipital montages (r(2) = 0.96; P = 0.03). It may be valid to measure BIS with
      the sensor on the occipital area if required during frontal neurosurgical
      procedures. IMPLICATIONS: Bispectral values were positively correlated when
      recorded from frontal and occipital sensors in patients undergoing clipping of
      unruptured cerebral aneurysms while anesthetized with propofol and fentanyl.

PMID- 15155345
TI  - Diagnosis of intracranial arterial stenosis using transcranial Doppler flowmetry.
AB  - In this case report we describe the use of transcranial Doppler flowmetry during
      induction of anesthesia in a patient with a large pituitary tumor. In this
      patient, both IV anesthesia induction and onset hyperventilation were followed by
      severe decreases of flow velocity in the middle cerebral artery of the affected
      side. Transcranial Doppler detected critical blood flow reduction in response to
      anesthesia induction and onset of hyperventilation in a brain tumor patient.

PMID- 15155346
TI  - The relative motor blocking potencies of intrathecal ropivacaine: effects of
      concentration.
AB  - This study established the median effective dose (ED(50)) for motor block of
      intrathecal 1% and 0.1% ropivacaine and determined the effects of the
      concentration of the solution injected on the motor block obtained. We enrolled
      into this prospective, randomized, double-blind, sequential allocation study 54
      parturients undergoing elective Cesarean delivery under combined spinal-epidural
      technique. Parturients were randomized to receive intrathecal ropivacaine either
      1% or 0.1%. The initial dose was chosen to be 4 mg, with subsequent doses being
      determined by the response of the previous patient (testing interval, 1 mg). The
      occurrence of any motor block in either lower limb within 5 min from the
      intrathecal injection of the study solution was considered effective. The motor
      block at 5 min was 6.1 mg for 1% ropivacaine (95% confidence interval [CI], 5.1
      7.1) and was 9.1 mg (95% CI, 7.8-10.3) for 0.1% ropivacaine (P = 0.0013; 95% CI
      difference, 1.3-4.7). The relative efficacy ratio of the 2 concentrations was 1.5
      (95% CI difference, 1.2-1.9) in favor of the larger concentration. The ED(50) of
      spinal ropivacaine to produce motor block in pregnant patients was significantly
      influenced by the concentration of the local anesthetic, with dose requirements
      being increased by 50% for the smaller concentration. IMPLICATIONS: The minimum
      local anesthetic dose for motor block with 0.1% ropivacaine is 50% larger than
      the 1% concentration with a relative efficacy ratio of 1.5. Our findings suggest
      that more diluted local anesthetic solutions determine less motor block, and this
      may be considered in ambulant laboring parturients.

PMID- 15155347
TI  - Pressure sore as a complication of labor epidural analgesia.
AB  - Lumbar epidural analgesia has become a common mode of pain control for laboring
      patients. Side effects, such as hypotension, motor blockade, respiratory
      depression, dural puncture, and urinary retention, are well described. Although
      pressure sores have been thought of as a complication limited to elderly,
      emaciated, unconscious, or bedridden patients, we describe the occurrence of
      pressure sores in a young and healthy parturient after lumbar epidural analgesia.
      IMPLICATIONS: We report a pressure sore that resulted from lumbar epidural
      analgesia for labor.

PMID- 15155348
TI  - Anterior approach to the sciatic nerve block: adaptation to the patient's height.
AB  - To improve the incidence of block of the posterior femoral cutaneous nerve (PFCN)
      when using an anterior approach as described recently, we hypothesized that the
      distance between the inguinal line and the puncture site depends on the patient's
      height. A preliminary radiological study performed in 13 patients established a
      formula describing the relationships between the patient's height and the
      puncture site "S." A line was drawn between the anterior iliac spine and the
      superior angle of the pubic tubercle (inguinal line) and another line from the
      midpoint of the inguinal line to the puncture site "S." "S" was calculated from
      the midpoint of the inguinal line as "S" = (height in cm--100)/10. A prospective
      study was conducted in 53 patients. Results are presented as median (range, 0.25
      0.75). Two minutes were required to locate the sciatic nerve at a depth of 12 cm
      (10.5-13.0 cm). Complete sciatic and PFCN blocks were observed in 92% of the
      patients. We conclude that consideration should be given to the patient's height
      when the sciatic nerve is blocked using an anterior approach. This technique
      seems to improve the success of block of the PFCN, essential to tolerate a thigh
      tourniquet. IMPLICATIONS: This prospective but noncomparative work was performed
      to evaluate a new anterior technique of sciatic block, an adaptation of the
      anatomic landmarks described by Chelly and Delaunay, to patient height.

PMID- 15155349
TI  - 0.5% versus 1.0% 2-chloroprocaine for intravenous regional anesthesia: a
      prospective, randomized, double-blind trial.
AB  - In this randomized prospective double-blind study we tested the hypothesis that
      compared with 40 mL chloroprocaine 0.5%, 40 mL chloroprocaine 1% results in an
      earlier onset to analgesia duration and improves distal tourniquet tolerance in
      150 patients undergoing forearm surgery under IV regional anesthesia using a
      double-cuff technique, switching from the proximal to the distal cuff was
      performed if pain scores increased above 4 of 10. Switching to the distal cuff
      resulted in pain scores below 4 in 69% of patients in the 0.5% group and in 88%
      of patients in the 1% group (P = 0.047). In addition, both groups differed in the
      sustained effect on distal tourniquet pain (P = 0.020). Time between injection
      and onset to analgesia duration was 13 +/- 1 min in the 0.5% group and 11 +/- 1
      min in the 1% group (P = 0.0006). On release of the tourniquet, signs of systemic
      local anesthetic toxicity occurred in 6 patients of the 0.5% group and 28 of the
      1% group (P < 0.0001). We conclude that chloroprocaine 1% resulted in an earlier
      onset of analgesia and improved distal tourniquet tolerance. However, these
      beneficial effects must be weighed against a fourfold increase in side effects.
      IMPLICATIONS: Compared to a standard dose of 40 mL 0.5% chloroprocaine, 40 mL 1%
      chloroprocaine resulted in an earlier onset of analgesia duration and improved
      distal tourniquet tolerance during IV regional anesthesia. These beneficial
      effects must be weighed against a fourfold increase in signs of systemic local
      anesthetic toxicity.

PMID- 15155350
TI  - Intracranial hypotension caused by cervical cerebrospinal fluid leak: treatment
      with epidural blood patch.
AB  - This report describes treatment with cervical epidural blood patch of low
      cerebrospinal fluid (CSF) pressure headache resulting from spontaneous CSF leak
      via a tear in a cervical dural cuff. The leak was diagnosed by a dynamic computed
      tomography (CT)-myelography study followed by gadolinium enhanced magnetic
      resonance imaging(MRI)-scan. The epidural needle was inserted with the aid of
      image intensifier and CT-scan to guide the needle to the precise site of the CSF
      leak. Blood mixed with gadolinium was injected, and subsequent MRI scanning
      provided the first description of spread of blood after cervical epidural blood
      patch. IMPLICATIONS: Low cerebrospinal fluid (CSF) pressure may cause severe
      posturally-related headache. In the patient, a vertebral disc protrusion in the
      neck seems to have contributed to a CSF leak. An injection of blood into the
      epidural space at the precise site of the CSF leak was followed by complete and
      lasting resolution of the headache.

PMID- 15155351
TI  - Brief postoperative delirium in hip fracture patients affects functional outcome
      at three months.
AB  - It is unclear how brief postoperative delirium (DEL) affects functional outcomes.
      In this study, we sought to determine if patients with brief postoperative DEL
      (<6-wk duration) have different living situations when compared with non-DEL
      patients after hip fracture repair. In a prospective study, patients admitted to
      the geriatric hip fracture service were assessed every postoperative day for the
      presence of DEL using the confusion assessment method (CAM) score. Patients were
      reassessed at 6 wk and 3 mo postoperatively for CAM score, current living
      situation, and activities of daily living. Group comparisons were tested after
      dividing patients into two groups: DEL (DEL; [+] CAM at any time during the
      postoperative period while in the hospital); no-DEL (no DEL; [-] CAM throughout
      the postoperative period while in the hospital). The study included 92 patients
      of whom 26 (28%) were CAM (+) after surgery. At 6 wk follow-up, n = 81; at 3 mo
      follow-up, n = 76. Eight patients died during the study. At 6 wk and 3 mo, a
      larger percentage of DEL patients were not living with a family member (27%
      versus 8% patients not living with a family member at 3 mo follow-up in DEL and
      no-DEL, respectively). There was no difference in activities of daily living by 3
      mo. We conclude that brief postoperative DEL lasting <6 wk is a determining
      factor for poor long-term functional outcome after hip fracture repair, because
      it significantly impacts the ability to live independently. IMPLICATIONS: Brief
      postoperative delirium lasting <6 wk is a determining factor for poor long-term
      functional outcome after hip fracture repair, because it significantly impacts
      the ability to live independently.

PMID- 15155352
TI  - Time-related cuff pressures of the laryngeal tube with and without the use of
      nitrous oxide.
AB  - The Laryngeal tube (VBM Medizintechnik, Sulz, Germany), a new supraglottic
      airway, consists of an airway tube, two cuffs, and two distal apertures between
      the two cuffs. One concern with the use of this device is ischemic change to the
      oropharyngeal mucosa. We studied the time-course change of the intracuff pressure
      (which reflects the pharyngeal pressure) of the laryngeal tube during anesthesia
      with and without nitrous oxide. After insertion of a laryngeal tube, 24 patients
      were randomly allocated to 1 of 2 groups. In one group (group N or nitrous oxide
      group), 66% nitrous oxide was used, whereas in the other group nitrous oxide was
      not used (group A or air group). In both groups, sevoflurane was used to maintain
      anesthesia. Time-course changes of the intracuff pressure and postoperative
      airway complications were recorded. In group N, the intracuff pressure
      significantly increased over time (P < 0.001; the maximal pressure: 120 cm
      H(2)O), whereas in group A the intracuff pressure remained stable. The intracuff
      pressure was significantly higher in group N than in group A (P < 0.0001; 95%
      confidence intervals for difference: 6-20 cm H(2)O at 30 min). Postoperatively,
      two patients in group A and one patient in group N complained of mild sore
      throat. IMPLICATIONS: Nitrous oxide may increase pharyngeal pressure by the cuffs
      of the laryngeal tube, and thus it is advisable to monitor and adjust the
      intracuff pressure of the laryngeal tube during anesthesia to minimize possible
      ischemic changes to the oropharynx.

PMID- 15155353
TI  - A severe complication after laser-induced damage to a transtracheal catheter
      during endoscopic laryngeal microsurgery.
AB  - Subcutaneous emphysema and pneumothorax is a rare and severe complication of
      percutaneous transtracheal jet ventilation, usually caused by obstruction of the
      upper airway or displacement of the tracheal catheter. Nevertheless, it is our
      preferred technique for endoscopic laryngeal laser surgery. We report a patient
      with acute subcutaneous emphysema and pneumothorax during laser surgery, caused
      by unobserved laser damage and discuss the associated risk factors. IMPLICATIONS:
      The percutaneous transtracheal jet ventilation for elective laryngeal laser
      surgery reduces the risk of airway fires and gives a free endoscopic operative
      field. This case report suggests that, even when using a teflon catheter, laser
      induced damage with severe complications might occur.

PMID- 15155354
TI  - "Black box" warning on droperidol: report of the FDA convened expert panel.

PMID- 15155356
TI  - BIS sensor electrodes can cause skin lesions: case report.

PMID- 15155355
TI  - Bariatric surgery and the prevention of postoperative respiratory complications.

PMID- 15155357
TI  - Financial disclosure.

PMID- 15155358
TI  - One view is no view.

PMID- 15155359
TI  - Unsuspected mechanical airway obstruction in obstructive sleep apnea syndrome.

PMID- 15155360
TI  - Spinal anesthesia in severe preeclampsia.

PMID- 15155361
TI  - Dexmedetomidine in pediatrics: controlled studies needed.

PMID- 15155362
TI  - Continuous monitoring of the end tidal CO2 ensures that the endotracheal tube
      remains in place during the removal of the LMA.

PMID- 15155363
TI  - Bullard laryngoscope proven useful in difficult intubations in children with
      Treacher Collins.

PMID- 15155364
TI  - "Quick look" direct laryngoscopy to avoid cannot intubate/cannot ventilate
      inductions.

PMID- 15155365
TI  - Ease placement of LMA ProSeal with a gastric tube inserted.

PMID- 15155366
TI  - A tale of two wires.

PMID- 15155367
TI  - Proteinaceous material on routinely cleaned laryngeal mask airways.

PMID- 15155368
TI  - Should the conventional method for routine tracheal intubation be questioned?

PMID- 15155371
TI  - Protective effect of sensory denervation in inflammatory arthritis (evidence of
      regulatory neuroimmune pathways in the arthritic joint).
AB  - OBJECTIVE: To investigate the direct effect of joint innervation on immune
      mediated joint inflammation in a patient with psoriatic arthritis (PsA). CASE
      REPORT: The patient developed arthritis mutilans in all digits of both hands with
      the exception of the left 4th finger, which had prior sensory denervation
      following traumatic nerve dissection. Plain radiography, ultrasonography and
      nerve conduction studies of the hands confirmed the absence of articular disease
      and sensory innervation in the left 4th digit. METHODS: This relationship between
      joint innervation and joint inflammation was investigated experimentally by prior
      surgical sensory denervation of the medial aspect of the knee in six Wistar rats
      in which carrageenan induced arthritis was subsequently induced. Prior sensory
      denervation--with preservation of muscle function--prevented the development of
      inflammatory arthritis in the denervated knee. DISCUSSION: Observations in human
      and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in
      the joint are an important mechanism that modulates the clinical expression of
      inflammatory arthritis.

PMID- 15155372
TI  - Premature atherosclerosis in primary antiphospholipid syndrome: preliminary data.
AB  - OBJECTIVE: To investigate the atherosclerosis hypothesis in primary
      antiphospholipid syndrome (PAPS). METHODS: The intima media thickness (IMT) of
      carotid arteries and other cardiovascular risk factors was measured in 20
      patients with PAPS (mean (SD) age 35 (12) years) and in 20 controls matched for
      age and sex (34 (12) years). RESULTS: The frequency of smoking, hypertension, and
      dyslipidaemia was similar in the two groups, but plasma homocysteine was higher
      in patients with PAPS (mean (SD) 11.9 (6.2) v 8.2 (3.4) micromol/l, p = 0.037).
      The IMT was slightly greater in patients with PAPS than in controls at the
      carotid bifurcation (mean (SD) 0.61 (0.24) v 0.48 (0.09) mm, p = 0.04) and
      internal carotid artery (0.52 (0.22) v 0.40 (0.08), p = 0.01). These differences
      were more evident in patients aged >40 years than in those aged <30 years at the
      carotid bifurcation (0.76 (0.25) v 0.55 (0.06), p = 0.0007) and internal carotid
      artery (0.63 (0.25) v 0.45 (0.09), p = 0.02); no differences were seen in the
      younger age group compared with controls. CONCLUSION: Atherosclerosis is a
      possibility in patients with PAPS in their fourth decade of life or older.

PMID- 15155373
TI  - Dermal exposure risk assessment.

PMID- 15155374
TI  - From individual leaf elongation to whole shoot leaf area expansion: a comparison
      of three Aegilops and two Triticum species.
AB  - BACKGROUND AND AIMS: Rapid leaf area expansion is a desirable trait in the early
      growth stages of cereal crops grown in low-rainfall areas. In this study, the
      traits associated with inherent variation in early leaf area expansion rates have
      been investigated in two wheat species (Triticum aestivum and T. durum) and three
      of its wild relatives (Aegilops umbellulata, A. caudata and A. tauschii) to find
      out whether the Aegilops species have a faster leaf area expansion in their early
      developmental stage than some of the current wheat species. METHODS: Growth of
      individual leaves, biomass allocation, and gas exchange were measured on
      hydroponically grown plants for 4 weeks. KEY RESULTS: Leaf elongation rate (LER)
      was strongly and positively correlated with leaf width but not with leaf
      elongation duration (LED). The species with more rapidly elongating leaves showed
      a faster increase with leaf position in LER, leaf width and leaf area, higher
      relative leaf area expansion rates, and more biomass allocation to leaf sheaths
      and less to roots. No differences in leaf appearance rate were found amongst the
      species. CONCLUSIONS: Aegilops tauschii was the only wild species with rapid leaf
      expansion rates similar to those of wheat, and it achieved the highest
      photosynthetic rates, making it an interesting species for further study.

PMID- 15155375
TI  - The effects of environmental heterogeneity on root growth and root/shoot
      partitioning.
AB  - AIMS: The purpose of this Botanical Briefing is to stimulate reappraisal of root
      growth, root/shoot partitioning, and analysis of other aspects of plant growth
      under heterogeneous conditions. SCOPE: Until recently, most knowledge of plant
      growth was based upon experimental studies carried out under homogeneous
      conditions. Natural environments are heterogeneous at scales relevant to plants
      and in forms to which they can respond. Responses to environmental heterogeneity
      are often localized rather than plant-wide, and not always predictable from
      traditional optimization arguments or from knowledge of the ontogenetic trends of
      plants growing under homogeneous conditions. These responses can have substantial
      impacts, both locally and plant-wide, on patterns of resource allocation, and
      significant effects on whole-plant growth. Results from recent studies are
      presented to illustrate responses of plants, plant populations and plant
      communities to nutritionally heterogeneous conditions. CONCLUSIONS: Environmental
      heterogeneity is a constant presence in the natural world that significantly
      influences plant behaviour at a variety of levels of complexity. Failure to
      understand its effects on plants prevents us from fully exploiting aspects of
      plant behaviour that are only revealed under patchy conditions. More effort
      should be invested into analysis of the behaviour of plants under heterogeneous
      conditions.

PMID- 15155377
TI  - The Causes of self-sterility in natural populations of the relictual angiosperm,
      Illicium floridanum (Illiciaceae).
AB  - BACKGROUND AND AIMS: Illicium floridanum, a species belonging to the basal extant
      angiosperm taxon Illiciaceae, reportedly exhibits self-incompatibility (SI). To
      date, the site and timing of SI within the carpel of this species remains
      unidentified. Thus, the objective of this research was to determine the cellular
      and temporal aspects of SI in I. floridanum. METHODS: Following controlled
      application of cross- and self-pollen in natural populations of I. floridanum,
      embryo sac development and temporal aspects of stigma receptivity, as well as
      pollen tube growth, fertilization, and embryo and endosperm development, were
      investigated with the aid of light and fluorescence microscopy. KEY RESULTS:
      Flowers of I. floridanum exhibited complete dichogamy whereby stigmas only
      supported cross- and self-pollen tube growth prior to anther dehiscence. In
      contrast to earlier reports of SI in this species, a prezygotic SI resulting in
      rejection of self-pollen tube growth at the stigma was absent and there were no
      significant differences between cross- versus self-pollen germination and pollen
      tube growth within the style and ovary during the first 5 d after pollination.
      Structural development of the four-celled embryo sac was not differentially
      influenced by pollen type as noted to occur in other angiosperms with late-acting
      ovarian SI. The ovule micropyle and embryo sac were penetrated equally by cross-
      and self-pollen tubes. In addition, there were no statistically significant
      differences in cross- versus self-fertilization. A resting zygote and
      multicellular endosperm at a variety of developmental stages was present by 30 d
      after application of cross- or self-pollen. CONCLUSIONS: In the clear absence of
      a prezygotic SI that was previously reported to result in differential self
      pollen tube growth at the stigma, self- sterility in I. floridanum is likely due
      to early-acting inbreeding depression, although late-acting post-zygotic ovarian
      SI cannot be ruled out.

PMID- 15155378
TI  - Changes in ion fluxes during phototropic bending of etiolated oat coleoptiles.
AB  - BACKGROUND AND AIMS: This work has been conducted to assist theoretical modelling
      of the different stages of the blue light (BL)-induced phototropic signalling
      pathway and ion transport activity across plant membranes. Ion fluxes (Ca(2+),
      H(+), K(+) and Cl(-)) in etiolated oat coleoptiles have been measured
      continuously before and during unilateral BL exposure. METHODS: Changes in ion
      fluxes at the illuminated (light) and shadowed (dark) sides of etiolated oat
      coleoptiles (Avena sativa) were studied using a non-invasive ion-selective
      microelectrode technique (MIFE). The bending response was also measured
      continuously, and correlations between the changes in various ion fluxes and
      bending response have been investigated. For each ion the difference (Delta)
      between the magnitudes of flux at the light and dark sides of the coleoptile was
      calculated. KEY RESULTS: Plants that demonstrated a phototropic bending response
      also demonstrated Ca(2+) influx into the light side approximately 20 min after
      the start of BL exposure. This is regarded as part of the perception and
      transduction stages of the BL-induced signal cascade. The first 10 min of bending
      were associated with substantial influx of H(+), K(+) and Cl(-) into the light
      (concave) side of the coleoptiles. CONCLUSIONS: The data suggest that Ca(2+)
      participates in the signalling stage of the BL-induced phototropism, whereas the
      phototropic bending response is linked to changes in the transport of H(+), K(+)
      and Cl(-).

PMID- 15155379
TI  - Investigation of genetic and morphological variation in the sago palm (Metroxylon
      sagu; Arecaceae) in Papua New Guinea.
AB  - BACKGROUND AND AIMS: The genetic and morphological variation in the sago palm
      (Metroxylon sagu, Arecaceae) in Papua New Guinea (PNG) was investigated. METHODS:
      Amplified fragment length polymorphism (AFLP) was used to investigate the genetic
      structure of 76 accessions of M. sagu, collected in seven wild and semi-wild
      stands in PNG. KEY RESULTS: An analysis of ten quantitative morphological
      variables revealed that most of these were mutually correlated. Principal
      component analyses of the same morphological variables showed that neither
      armature (presence or absence of spines) nor geographical separation was
      reflected clearly in the quantitative morphological variation. Similarity
      matrices of genetic, quantitative morphological, geographical and armature data
      were tested for pair-wise correlations, using Mantel's test. The results only
      showed a significant correlation between genetic and geographical distances.
      Visual inspection of principal component analyses plots and a neighbour-joining
      dendrogram based on genetic distances supported this trend, whereas armature
      showed no relation with genetic distances. CONCLUSIONS: Geographical distribution
      defines some weak patterns in the genetic variation, whereas the genetic
      variation does not reflect any patterns in the morphological variation, including
      armature. The present study supports the accepted taxonomy of M. sagu,
      recognizing only one species of M. sagu in PNG.

PMID- 15155380
TI  - Recovery of leaf area through accelerated shoot ontogeny in thrips-damaged cotton
      seedlings.
AB  - BACKGROUND AND AIMS: Leaf area of cotton seedlings (Gossypium hirsutum) can be
      reduced by as much as 50 % by early season thrips infestations, but it is well
      documented that plants can regain the difference in leaf area once infestation
      ceases. The processes involved in the recovery have not been identified.
      Hypotheses include enhancement of the photosynthetic rate of the damaged leaves,
      more efficient leaf construction (i.e. more leaf area per unit of dry matter
      invested in new leaves), and more branching. METHODS: This 2-year field study
      examined these hypotheses and found that thrips-affected plants recovered from a
      30 % reduction in total leaf area. During the recovery period, repeated
      measurements of gas exchange, leaf morphology and individual leaf areas at all
      nodes were made to assess their contribution to the recovery. KEY RESULTS:
      Recovery was not achieved through the previously proposed mechanisms. The pattern
      of nodal development indicated that the duration of leaf expansion of the smaller
      deformed leaves was shorter than that of control leaves, possibly because they
      had fewer cells. The production and expansion of healthy upper node leaves in
      thrips-affected plants could, therefore, begin sooner, about 1-2.5 nodes in
      advance of control plants. The proposed process of recovery was evident but
      weaker in the second year where thrips numbers were higher. CONCLUSIONS: It is
      concluded that thrips-affected plants overcame the leaf area disparity through an
      accelerated ontogeny of main stem leaves. By completing the expansion of smaller
      but normally functioning lower node leaves earlier, resources were made available
      to the unfolding of larger upper node leaves in advance of control plants. The
      generality of this mode of plant resistance in pest damage remains to be
      determined.

PMID- 15155381
TI  - RAGE axis: Animal models and novel insights into the vascular complications of
      diabetes.
AB  - Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin
      superfamily of cell surface molecules. Engagement of RAGE by its signal
      transduction ligands evokes inflammatory cell infiltration and activation in the
      vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and
      superimposed stresses such as hyperlipidemia or acute balloon/endothelial
      denuding arterial injury, the ligand-RAGE axis amplifies vascular stress and
      accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we
      review the use of rodent models to test these concepts. Taken together, our
      findings support the premise that RAGE is an amplification step in vascular
      inflammation and acceleration of atherosclerosis. Future studies must rigorously
      test the potential impact of RAGE blockade in human subjects; such trials are on
      the horizon.

PMID- 15155382
TI  - Balance between PGD synthase and PGE synthase is a major determinant of
      atherosclerotic plaque instability in humans.
AB  - OBJECTIVE: Inducible cyclooxygenase (COX-2) catalyzes the first step in
      prostanoid biosynthesis and is considered a proinflammatory enzyme. COX-2 and
      type 1 inducible PGE synthase (mPGES-1) have a role in metalloproteinase (MMP)
      release leading to plaque rupture. In contrast, lipocalin-type PGD synthase (L
      PGDS) has been shown to exert antiinflammatory actions. Thus, in this study we
      investigated whether a shift from a PGDS-oriented to a PGES-oriented profile in
      arachidonate metabolism leads to inflammatory activation in rupture-prone plaque
      macrophages. METHODS AND RESULTS: Atherosclerotic plaques were obtained from 60
      patients who underwent carotid endarterectomy, symptomatic (n=30) and
      asymptomatic (n=30) according to evidence of recent transient ischemic attack or
      stroke. Plaques were analyzed for COX-2, mPGES-1, L-PGDS, PPARgamma,
      IkappaBalpha, NF-kappaB, and MMP-9 by immunocytochemistry, Western blot, reverse
      transcriptase polymerase chain reaction, enzyme immunoassay, and zymography.
      Prostaglandin E2 (PGE2) pathway was significantly prevalent in symptomatic
      plaques, whereas PGD2 pathway was overexpressed in asymptomatic ones, associated
      with NF-kappaB inactivation and MMP-9 suppression. In vitro COX-2 inhibition in
      monocytes was associated with reduced MMP-9 release only when PGD2 pathway
      overcame PGE2 pathway. CONCLUSIONS: These results suggest that COX-2 may have
      proinflammatory and antiinflammatory properties as a function of expression of
      downstream PGH2 isomerases, and that the switch from L-PGDS to mPGES-1 in plaque
      macrophages is associated with cerebral ischemic syndromes, possibly through MMP
      induced plaque rupture.

PMID- 15155376
TI  - Eukaryotic cells and their cell bodies: Cell Theory revised.
AB  - BACKGROUND: Cell Theory, also known as cell doctrine, states that all eukaryotic
      organisms are composed of cells, and that cells are the smallest independent
      units of life. This Cell Theory has been influential in shaping the biological
      sciences ever since, in 1838/1839, the botanist Matthias Schleiden and the
      zoologist Theodore Schwann stated the principle that cells represent the elements
      from which all plant and animal tissues are constructed. Some 20 years later, in
      a famous aphorism Omnis cellula e cellula, Rudolf Virchow annunciated that all
      cells arise only from pre-existing cells. General acceptance of Cell Theory was
      finally possible only when the cellular nature of brain tissues was confirmed at
      the end of the 20th century. Cell Theory then rapidly turned into a more dogmatic
      cell doctrine, and in this form survives up to the present day. In its current
      version, however, the generalized Cell Theory developed for both animals and
      plants is unable to accommodate the supracellular nature of higher plants, which
      is founded upon a super-symplasm of interconnected cells into which is woven
      apoplasm, symplasm and super-apoplasm. Furthermore, there are numerous examples
      of multinucleate coenocytes and syncytia found throughout the eukaryote
      superkingdom posing serious problems for the current version of Cell Theory.
      SCOPE: To cope with these problems, we here review data which conform to the
      original proposal of Daniel Mazia that the eukaryotic cell is composed of an
      elemental Cell Body whose structure is smaller than the cell and which is endowed
      with all the basic attributes of a living entity. A complement to the Cell Body
      is the Cell Periphery Apparatus, which consists of the plasma membrane associated
      with other periphery structures. Importantly, boundary structures of the Cell
      Periphery Apparatus, although capable of some self-assembly, are largely produced
      and maintained by Cell Body activities and can be produced from it de novo. These
      boundary structures serve not only as mechanical support for the Cell Bodies but
      they also protect them from the hostile external environment and from
      inappropriate interactions with adjacent Cell Bodies within the organism.
      CONCLUSIONS: From the evolutionary perspective, Cell Bodies of eukaryotes are
      proposed to represent vestiges of hypothetical, tubulin-based 'guest' proto
      cells. After penetrating the equally hypothetical actin-based 'host' proto-cells,
      tubulin-based 'guests' became specialized for transcribing, storing and
      partitioning DNA molecules via the organization of microtubules. The Cell
      Periphery Apparatus, on the other hand, represents vestiges of the actin-based
      'host' proto-cells which have become specialized for Cell Body protection, shape
      control, motility and for actin-mediated signalling across the plasma membrane.

PMID- 15155383
TI  - Enhanced P2X7 activity in human fibroblasts from diabetic patients: a possible
      pathogenetic mechanism for vascular damage in diabetes.
AB  - OBJECTIVE: We have investigated expression and function of the P2X7 receptor in
      fibroblasts from healthy subjects and patients with type 2 diabetes. METHODS AND
      RESULTS: Fibroblasts were isolated from skin biopsies. P2X7 receptor expression
      in both cell populations was measured by functional assays, RT-PCR, fluorescence
      activated cell sorter, and immunoblotting. We found that fibroblasts from
      diabetic subjects are characterized by enhanced P2X7-mediated responses as
      indicated by increased shape changes, microvesiculation, enhanced fibronectin and
      interleukin 6 secretion, and accelerated apoptosis. These responses were blocked
      by preincubation with the P2X blockers KN-62, oxidized ATP, or pyridoxal
      phosphate-6-azo(benzene-2,4-disulfonic acid). Furthermore, we also found a higher
      level of spontaneous fibronectin secretion and of apoptosis in fibroblasts from
      diabetic compared with healthy subjects. Both higher basal level of fibronectin
      secretion and spontaneous rate of apoptosis were likely attributable to the
      increased pericellular concentration of ATP because fibroblasts from diabetic
      subjects released 3x as much ATP into the supernatants compared with fibroblasts
      from healthy subjects. CONCLUSIONS: We conclude that fibroblasts from type 2
      diabetes patients are characterized by a hyperactive purinergic loop based either
      on a higher level of ATP release or on increased P2X7 reactivity.

PMID- 15155384
TI  - Vascular calcification: mechanisms and clinical ramifications.
AB  - Vascular calcification, long thought to result from passive degeneration,
      involves a complex, regulated process of biomineralization resembling
      osteogenesis. Evidence indicates that proteins controlling bone mineralization
      are also involved in the regulation of vascular calcification. Artery wall cells
      grown in culture are induced to become osteogenic by inflammatory and atherogenic
      stimuli. Furthermore, osteoclast-like cells are found in calcified
      atherosclerotic plaques, and active resorption of ectopic vascular calcification
      has been demonstrated. In general, soft tissue calcification arises in areas of
      chronic inflammation, possibly functioning as a barrier limiting the spread of
      the inflammatory stimulus. Atherosclerotic calcification may be one example of
      this process, in which oxidized lipids are the inflammatory stimulus.
      Calcification is widely used as a clinical indicator of atherosclerosis. It
      progresses nonlinearly with time, following a sigmoid-shaped curve. The
      relationship between calcification and clinical events likely relates to
      mechanical instability introduced by calcified plaque at its interface with
      softer, noncalcified plaque. In general, as calcification proceeds, interface
      surface area increases initially, but eventually decreases as plaques coalesce.
      This phenomenon may account for reports of less calcification in unstable plaque.
      Vascular calcification is exacerbated in certain clinical entities, including
      diabetes, menopause, and osteoporosis. Mechanisms linking them must be considered
      in clinical decisions. For example, treatments for osteoporosis may have
      unanticipated effects on vascular calcification; the converse also applies.
      Further understanding of processes governing vascular calcification may yield new
      therapeutic options for vascular disease.

PMID- 15155385
TI  - Decreased number and impaired angiogenic function of endothelial progenitor cells
      in patients with chronic renal failure.
AB  - OBJECTIVE: Increased risk of cardiovascular disease in patients with chronic
      renal failure (CRF) has been explained by accelerated atherosclerosis and
      impaired angiogenesis, in which endothelial progenitor cells (EPCs) may play key
      roles. We hypothesized that altered EPC biology may contribute to the
      pathophysiology of CRF. METHODS AND RESULTS: EPCs were isolated from CRF patients
      on maintenance hemodialysis (n=44) and from a normal control group (n=30). CRF
      patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%)
      when compared with the controls (P<0.001). These findings were corroborated by
      30.5% decrease in EPC migratory function in response to vascular endothelial
      growth factor (VEGF) (P=0.040) and 48.8% decrease in EPC incorporation into human
      umbilical vein endothelial cells (HUVEC) (P<0.001). In addition, Framingham's
      risk factor score of both CRF (r=-0.461, P=0.010) and normal group (r=-0.367,
      P=0.016) significantly correlated with the numbers of EPC. Indeed, the number of
      circulating EPC was significantly lower in CRF patients than in normal group
      under the same burden of risk factors (P<0.001). A significant correlation was
      also observed between dialysis dose (Kt/V) and EPC incorporation into HUVEC
      (r=0.427, P=0.004). CONCLUSIONS: EPC biology, which is critical for
      neovascularization and the maintenance of vascular function, is altered in CRF.
      Our data strongly suggest that dysfunction of circulating EPC has a role in the
      progression of cardiovascular disease in patients with CRF.

PMID- 15155386
TI  - Screening for coeliac disease: what evidence is required before population
      programmes could be considered?

PMID- 15155387
TI  - Health needs of children in prison.

PMID- 15155388
TI  - Periorificial dermatitis with dramatic response to zinc.

PMID- 15155389
TI  - Understanding the rising incidence of type 2 diabetes in adolescence.

PMID- 15155390
TI  - Developing multi-faith chaplaincy.

PMID- 15155391
TI  - The effects of a double blind, placebo controlled, artificial food colourings and
      benzoate preservative challenge on hyperactivity in a general population sample
      of preschool children.
AB  - AIMS: To determine whether artificial food colourings and a preservative in the
      diet of 3 year old children in the general population influence hyperactive
      behaviour. METHODS: A sample of 1873 children were screened in their fourth year
      for the presence of hyperactivity at baseline (HA), of whom 1246 had skin prick
      tests to identify atopy (AT). Children were selected to form the following
      groups: HA/AT, not-HA/AT, HA/not-AT, and not-HA/not-AT (n = 277). After baseline
      assessment, children were subjected to a diet eliminating artificial colourings
      and benzoate preservatives for one week; in the subsequent three week within
      subject double blind crossover study they received, in random order, periods of
      dietary challenge with a drink containing artificial colourings (20 mg daily) and
      sodium benzoate (45 mg daily) (active period), or a placebo mixture,
      supplementary to their diet. Behaviour was assessed by a tester blind to dietary
      status and by parents' ratings. RESULTS: There were significant reductions in
      hyperactive behaviour during the withdrawal phase. Furthermore, there were
      significantly greater increases in hyperactive behaviour during the active than
      the placebo period based on parental reports. These effects were not influenced
      by the presence or absence of hyperactivity, nor by the presence or absence of
      atopy. There were no significant differences detected based on objective testing
      in the clinic. CONCLUSIONS: There is a general adverse effect of artificial food
      colouring and benzoate preservatives on the behaviour of 3 year old children
      which is detectable by parents but not by a simple clinic assessment. Subgroups
      are not made more vulnerable to this effect by their prior levels of
      hyperactivity or by atopy.

PMID- 15155393
TI  - Forearm blood glucose testing in diabetes mellitus.
AB  - AIMS: To compare the accuracy and acceptability of capillary blood glucose
      testing from the forearm with finger prick testing in diabetic children. METHODS:
      Blood glucose measurements from samples taken from the forearm and the finger
      were compared in an outpatient setting from 52 children and adolescents with
      diabetes mellitus aged 6-17 years. Opinions on forearm sampling were collected by
      questionnaire. RESULTS: Blood glucose results obtained from forearm sampling
      correlated well with results from the finger measured by the Yellow Springs
      Instrument analyser. Error grid analysis showed that 100% of measurements were
      clinically acceptable; 61% of children reported that forearm testing was painless
      and 19% that it was less painful than finger prick testing. CONCLUSION: Forearm
      testing is an acceptable alternative to finger prick testing for blood glucose
      measurement in children and adolescents.

PMID- 15155392
TI  - Mass screening for coeliac disease using antihuman transglutaminase antibody
      assay.
AB  - AIMS: To determine coeliac disease prevalence by an anti-transglutaminase
      antibody assay in a large paediatric population; to evaluate acceptance of the
      screening programme, dietary compliance, and long term health effects. METHODS:
      Cross-sectional survey of 3188 schoolchildren (aged 6-12) and prospective follow
      up of diagnosed cases. Main outcome measures were: prevalence of coeliac disease
      defined by intestinal biopsy or positivity to both human tissue transglutaminase
      and anti-endomysium antibodies in HLA DQ2-8 positive subjects; percentage of
      children whose families accepted screening; dietary compliance as defined by
      negativity for anti-transglutaminase antibodies; and presence of clinical or
      laboratory abnormalities at 24 month follow up. RESULTS: The families of
      3188/3665 children gave their consent (87%). Thirty biopsy proven coeliacs were
      identified (prevalence 1:106). Three other children testing positive for both
      coeliac related autoantibodies and HLA DQ2-8 but refusing biopsy were considered
      as having coeliac disease (prevalence 1:96). Of 33 cases, 12 had coeliac related
      symptoms. The 30 biopsy proven coeliacs followed a gluten-free diet. Of 28
      subjects completing 18-24 months follow up, 20 (71.4%) were negative for anti
      transglutaminase antibodies, while eight were slightly positive; symptoms
      resolved in all 12 symptomatic children. CONCLUSIONS: Prevalence of coeliac
      disease is high in Italian schoolchildren. Two thirds of cases were asymptomatic.
      Acceptance of the programme was good, as was dietary compliance. Given the high
      prevalence and possible complications of untreated coeliac disease, the
      availability of a valid screening method, and evidence of willingness to comply
      with dietary treatment population mass screening deserves careful consideration.

PMID- 15155394
TI  - Impact of a general practice based group parenting programme: quantitative and
      qualitative results from a controlled trial at 12 months.
AB  - AIMS: To test the effectiveness at one year of the Webster Stratton Parents and
      Children Series group parenting programme in a population sample of parents.
      METHODS: In a multicentre block randomised controlled trial, parents of children
      aged 2-8 years in 116 families who scored in the upper 50% on a validated
      behaviour inventory, took part in Webster-Stratton's 10 week parenting programme
      led by trained and supervised health visitors. The following outcome measures
      were used: Eyberg Child Behaviour Inventory, Goodman Strengths and Difficulties
      Questionnaire, General Health Questionnaire, Parenting Stress Index, Rosenberg
      Self Esteem Scale. RESULTS: The intervention significantly reduced child
      behaviour problems and improved mental health at immediate and 6 month follow
      ups. One year differences between control and intervention groups were not
      significant. Qualitative results suggest that these findings might be
      attributable in part to either Hawthorne effects or contamination of control
      group. At interview parents described ways in which the programme had improved
      their mental health. They reported gains in confidence and feeling less stressed.
      Some also reported beneficial changes in their own and their children's behaviour
      and improved relationships with their children. Some spoke of a need for further
      sessions to support the behaviour changes they had managed to make, and some the
      desire for attendance by both parents. CONCLUSIONS: Parenting programmes have the
      potential to promote mental health and reduce social inequalities, but further
      work is needed to improve long term effectiveness.

PMID- 15155395
TI  - First UK survey of paediatric type 2 diabetes and MODY.
AB  - AIMS: To estimate the UK prevalence of childhood type 2 diabetes and maturity
      onset diabetes of the young (MODY), and distinguish them from each other and from
      type 1 diabetes. METHODS: The British Society for Paediatric Endocrinology and
      Diabetes Clinical Trials/Audit Group undertook a cross-sectional questionnaire
      survey of all paediatric diabetes centres during 2000, collecting data on all
      children with non-type 1 diabetes. RESULTS: Of 112 children reported to the
      survey, 25 had type 2 diabetes and 20 had MODY. In contrast to type 1, type 2
      patients presented later (12.8 v 9.3 years), were usually female, overweight, or
      obese (92% v 28%), and a greater proportion were of ethnic minority origin (56% v
      22%). In contrast to type 2, MODY patients were younger (10.8 years), less likely
      to be overweight or obese (50% v 92%), and none were from ethnic minority groups.
      The crude minimum UK prevalence of type 2 diabetes under 16 years is 0.21/100
      000, and of MODY is 0.17/100 000. South Asian children have a relative risk of
      type 2 diabetes of 13.7 compared to white UK children. CONCLUSIONS: UK children
      still have a low prevalence of type 2 diabetes. Children from ethnic minorities
      are at significantly higher risk, but in white UK children with non-type 1
      diabetes a diagnosis of MODY is as likely as type 2 diabetes. Childhood type 2
      diabetes is characterised by insulin resistance, and is distinct from both type 1
      and MODY.

PMID- 15155396
TI  - The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis
      complex.
AB  - BACKGROUND: The aetiology of the learning difficulty in tuberous sclerosis is
      debated. It may be related to the amount of tubers in the brain or caused by the
      infantile spasms that occur in early life. AIMS: To examine the relative
      contributions to final intelligence (IQ) made by both cerebral tubers and
      infantile spasms. METHODS: As part of an epidemiological study of tuberous
      sclerosis in the south of England, patients were recruited who were able to
      undergo magnetic resonance imaging (MRI) without the need for an anaesthetic.
      Epilepsy history was determined by interview and review of clinical records. IQ
      was assessed using either Wechsler intelligence scales or Raven's matrices.
      RESULTS: A total of 41 patients consented to have an MRI scan. IQ scores were
      normally distributed about a mean of 91. Twenty six patients had a positive
      history of epilepsy, and 11 had suffered from infantile spasms. There was a
      significant relation between the number of tubers and IQ. Infantile spasm status
      partly confounded the relation between tubers and IQ, but did not render the
      relation statistically insignificant. The relation between infantile spasms and
      learning difficulty remained strong even when controlling for the number of
      tubers.

PMID- 15155398
TI  - Gastrostomy feeding in cerebral palsy: a systematic review.
AB  - AIMS: To determine benefits and risks for gastrostomy or jejunostomy feeding
      compared with oral feeding for children with cerebral palsy. METHODS: Systematic
      review. SEARCH STRATEGY: electronic databases--Cochrane Library, Medline, Embase,
      Cinahl, Lilacs, databases of theses, grey literature. INCLUDED: relevant
      systematic reviews, randomised controlled trials, observational studies, case
      reports. EXCLUDED: non-systematic reviews and qualitative research. PARTICIPANTS:
      children with cerebral palsy. INTERVENTION: use of gastrostomy or jejunostomy
      tube to provide nutrition. OUTCOME: evaluated outcome measures included death,
      growth, gastro-oesophageal reflux, other complications, psychosocial aspects, and
      caregiver wellbeing. RESULTS: No relevant systematic reviews or randomised
      controlled trials were found. Two cohort studies, 15 case series, and eight case
      reports met the inclusion criteria. Eight studies specifically described
      percutaneous endoscopic gastrostomy as the intervention. Weight gain resulted
      from gastrostomy feeding in most cases. There was an approximately fourfold
      increased risk of death reported in one cohort study for the gastrostomy fed
      children. Many complications were reported, including potential for increased
      gastro-oesophageal reflux and fluid aspiration into the lungs. CONCLUSIONS:
      Benefits associated with gastrostomy or jejunostomy feeding are difficult to
      assess from the available evidence. Risks of gastrostomy, particularly in
      relation to surgical complications, have been described but the size of the risk
      could not be quantified. The finding of a higher death rate for children fed by
      gastrostomy may merely reflect the greater disability of these compared with
      orally fed children. Lack of available evidence and the substantial risk of bias
      in observational studies suggests that a well conducted randomised controlled
      trial of sufficient size will be needed to answer these problems.

PMID- 15155400
TI  - Using child reported respiratory symptoms to diagnose asthma in the community.
AB  - AIMS: To study how respiratory symptoms reported by children, with or without
      spirometry, could help to discriminate those with asthma from those without.
      METHODS: Respiratory symptoms (frequent cough, frequent phlegm, and wheezing)
      reported by 1646 schoolchildren (aged 8-12 years) in a respiratory questionnaire
      and the FEV1:FVC ratio measured with spirometry (at three different cut-off
      values of 0.70, 0.75, and 0.80) were compared against the criterion standard of a
      physician diagnosis of asthma reported by the parents. RESULTS: The overall
      prevalence of asthma was 6%; more boys had asthma. Wheezing had the best
      discriminating ability among the three symptoms and a cut-off point at 75% was
      best for the FEV1:FVC ratio. Combining wheezing with an FEV1:FVC ratio <75% gave
      the highest discriminating ability of 83%. If the tests were applied to
      hypothetical populations with higher prevalence ratios of asthma, the added value
      of the FEV1:FVC ratio became less apparent. CONCLUSION: Respiratory symptoms,
      especially wheezing, reported by children had good discriminating ability for
      asthma and could be adopted for opportunistic screening in the primary care
      settings.

PMID- 15155399
TI  - Reported versus confirmed wheeze and lung function in early life.
AB  - AIMS: To investigate the relation between parentally reported wheeze
      (unconfirmed), physician confirmed wheeze, and subsequent lung function. METHODS:
      Children at risk of allergic disease (one parent atopic) were recruited
      antenatally and followed prospectively from birth. During the first three years
      of life parents were asked to contact the study team if their child was wheezy.
      The presence of wheeze was confirmed or not by the primary care or study
      physician. Respiratory questionnaire and specific airway resistance measurement
      (sR(aw), body plethysmograph) were completed at age 3 years. RESULTS: A total of
      454 children were followed from birth to 3 years of age. One hundred and eighty
      six (40.9%) of the parents reported their child wheezing in the first three years
      of life, and in 130 (28.6%) the wheeze was confirmed. A total of 428 children
      attended the three year clinic review, of whom 274 (64%) successfully carried out
      lung function tests. There was no significant difference in sR(aw) (kPa.s;
      geometric mean, 95% CI) between children who had never wheezed (n = 152; 1.03,
      1.00 to 1.06) and those with a parentally reported but unconfirmed wheeze (n =
      36; 1.02, 0.96 to 1.07, p = 1.00). sR(aw) was significantly higher in children
      with a physician confirmed wheeze (n = 86; 1.17, 1.11 to 1.22, p < 0.001)
      compared to those with no history of wheeze or with unconfirmed wheeze.
      CONCLUSIONS: Children with physician confirmed wheeze have significantly poorer
      lung function compared to those with parentally reported but unconfirmed and
      those who have never wheezed. A proportion of parents may have little
      understanding of what medical professionals mean by the term "wheeze".

PMID- 15155401
TI  - Health needs of children in prison.
AB  - At the end of September 2002 there were 2633 children in prison in England and
      Wales. Since November 2002, the Children Act 1989 applies to children held in
      prison. The challenge to paediatricians is to recognise and meet the needs of
      these vulnerable and needy children. This can be achieved by putting in place
      similar provisions to those recommended for Looked After Children.

PMID- 15155402
TI  - Severe acute respiratory syndrome in Singapore.
AB  - AIMS: To describe the epidemiological and clinical features of paediatric severe
      acute respiratory syndrome (SARS) in Singapore. METHODS: The following data were
      retrospectively collected from the case records of all 71 patients (aged 7 months
      to 14 years) admitted from 23 March to 22 May 2003 to the SARS paediatric unit:
      patient demographics, contact history, clinical features, physiological
      parameters, investigations, treatment, and outcome. Using WHO criteria there were
      seven probable (P), 23 suspect (S), and 41 observe (O) cases. RESULTS: Compared
      to the O cases P patients had a longer mean duration of fever (3.66 (SD 2.3) v
      8.57 (SD 2.44) days), lower mean thrombocytopenia (248.3 (SD 82.7) v 173.7 (SD
      49.0)x10(9)/l), leucopenia (8.19 (SD 4.45) v 3.06 (SD 1.02)x10(9)/l), lymphopenia
      (2.79 (SD 1.97) v 1.44 (SD 0.75)x10(9)/l), and neutropenia (4.48 (SD 2.88) v 1.24
      (SD 0.43)x10(9)/l). Chest auscultation was abnormal in 71% of P patients, with
      mild crepitations detected. All had abnormal chest radiographs versus 39% of S
      cases, and 27% of O cases. CONCLUSIONS: There are no distinguishing clinical
      features of paediatric SARS. The diagnosis is suggested by the paucity of
      clinical signs with an abnormal chest radiograph, and laboratory evidence of
      leucopenia, lymphopenia, and thrombocytopenia.

PMID- 15155403
TI  - Home based therapy for severe malnutrition with ready-to-use food.
AB  - BACKGROUND: The standard treatment of severe malnutrition in Malawi often
      utilises prolonged inpatient care, and after discharge results in high rates of
      relapse. AIMS: To test the hypothesis that the recovery rate, defined as catch-up
      growth such that weight-for-height z score >0 (WHZ, based on initial height) for
      ready-to-use food (RTUF) is greater than two other home based dietary regimens in
      the treatment of malnutrition. METHODS: HIV negative children >1 year old
      discharged from the nutrition unit in Blantyre, Malawi were systematically
      allocated to one of three dietary regimens: RTUF, RTUF supplement, or blended
      maize/soy flour. RTUF and maize/soy flour provided 730 kJ/kg/day, while the RTUF
      supplement provided a fixed amount of energy, 2100 kJ/day. Children were followed
      fortnightly. Children completed the study when they reached WHZ >0, relapsed, or
      died. Outcomes were compared using a time-event model. RESULTS: A total of 282
      children were enrolled. Children receiving RTUF were more likely to reach WHZ >0
      than those receiving RTUF supplement or maize/soy flour (95% v 78%, RR 1.2, 95%
      CI 1.1 to 1.3). The average weight gain was 5.2 g/kg/day in the RTUF group
      compared to 3.1 g/kg/day for the maize/soy and RTUF supplement groups. Six months
      later, 96% of all children that reached WHZ >0 were not wasted. CONCLUSIONS: Home
      based therapy of malnutrition with RTUF was successful; further operational work
      is needed to implement this promising therapy.

PMID- 15155404
TI  - Lower respiratory tract illness and RSV prophylaxis in very premature infants.
AB  - AIMS: To determine the frequency of and the risk factors for readmissions for any
      lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV)
      documented LRTI in children born very prematurely who had or had not received RSV
      prophylaxis. METHODS: Multicentre prospective longitudinal cohort study of 2813
      infants, born between April 2000 and December 2000 at less than 33 weeks of
      gestational age, and followed until the end of the epidemic season. RESULTS:
      Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of
      postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were
      readmitted at least once for any reason during the epidemic season; 15.1% and
      7.2% were readmitted at least once for any LRTI and RSV related LRTI,
      respectively. Children born at less than 31 weeks' gestation, having an
      intrauterine growth restriction, or living in a single mother family were at a
      significantly higher risk of readmission for LRTI in general as well as for RSV
      related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted
      at least once for any LRTI and 6.1% for RSV related LRTI. CONCLUSION: One out of
      four children who had received no prophylaxis, was born very prematurely, and was
      without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was
      readmitted at least once for any reason. Roughly 50% and 20% of these
      readmissions were related to a LRTI and an RSV infection, respectively. Further
      epidemiological studies are warranted to assess the aetiology and impact of other
      respiratory pathogens on post-discharge readmission and respiratory morbidity in
      this population.

PMID- 15155405
TI  - Bacteraemia due to Staphylococcus aureus.
AB  - AIMS: To describe the clinical features and outcome of bacteraemia due to
      Staphylococcus aureus in children admitted to a rural Kenyan hospital. METHODS:
      Retrospective case review of all children with a positive blood culture for S
      aureus admitted to Kilifi District Hospital, Kenya, between January 1996 and
      December 2001. RESULTS: Ninety seven children (median age 17 months, range 1 day
      to 12 years; 46 male) with bacteraemia due to S aureus were identified,
      accounting for 5% of all positive blood cultures; 10 were considered to be
      nosocomially acquired. A focus that was clinically consistent with staphylococcal
      infection was identified in 52 cases; of these, 88% had multiple foci. Children
      with a focus were likely to be older, present later, and have a longer duration
      of hospital stay. Most children in this group (90%) received intravenous
      cloxacillin on admission in contrast to none of those without a focus. In the
      former group, mortality was only 6% compared to 47% among those without a focus;
      10/13 neonates without an apparent staphylococcal focus died compared to none of
      the 11 with a focus. Eight of the 10 neonates in the former group died within 48
      hours of admission, before empirical antibiotics could be changed to include
      cloxacillin. CONCLUSIONS: Children most at risk of death associated with
      bacteraemia due to S aureus are least likely to have clinical features
      traditionally associated with this infection.

PMID- 15155406
TI  - Types of anaemic crises in paediatric patients with sickle cell anaemia seen in
      Enugu, Nigeria.
AB  - BACKGROUND: Anaemic crises in paediatric patients with sickle cell anaemia are
      major causes of morbidity and mortality. Some children admitted to hospitals'
      emergency rooms or paediatric wards of the hospitals with severe anaemia die
      before blood transfusion. AIMS AND METHODS: A total of 108 episodes of anaemic
      crises were prospectively evaluated in 108 patients with sickle cell anaemia
      attending the paediatric sickle cell clinic of the University of Nigeria Teaching
      Hospital, Enugu, Nigeria. RESULTS: Hyper-haemolytic crises were the commonest
      types of anaemic crises in the patients studied. The mean haemoglobin
      concentration of 44.66 (SD 6.42) g/l in crises was significantly lower than the
      mean steady state level of 78.69 (SD 8.50) g/l. Reticulocytes, unconjugated serum
      bilirubin concentrations, and the presence of nucleated red blood cells were also
      increased. About 4.6% of patients were not jaundiced at presentation even though
      they were profoundly anaemic. Their haematological indices gradually returned to
      normal without marked changes in their serum bilirubin concentrations. These
      patients were probably in the early recovery phase of aplastic crises. The
      classical presentation of acute splenic sequestration crisis with a rapidly
      enlarging spleen and hypotension was not observed. This was probably because of
      its precipitate nature and accompanying circulatory collapse, which carried a
      high mortality rate. Minor forms of sequestration crises may have occurred in the
      liver and spleen. CONCLUSIONS: Malaria appeared to have played a role in
      precipitating some of the hyper-haemolytic episodes. Further studies to elucidate
      this role are required so that appropriate recommendations regarding malaria
      prophylaxis can be made in patients with sickle cell anaemia.

PMID- 15155407
TI  - Cough plate versus cough swab in patients with cystic fibrosis; a pilot study.
AB  - BACKGROUND: Accurate identification of lower respiratory tract pathogens is
      important in the management of cystic fibrosis patients. AIM: To evaluate the
      cough plate as an alternative method of obtaining respiratory samples for
      microbiological culture. METHODS AND RESULTS: Using sputum culture as the "gold
      standard", the cough plate method identified significantly more positive cases
      than either dry or moistened cough swabs. Of 20 patients who had a positive
      sputum culture, 16 had a positive culture on cough plate compared to seven
      positive cultures each on moistened swab and on dry swab respectively.
      CONCLUSIONS: In this study cough plates were more sensitive than cough swabs in
      isolating respiratory pathogens in sputum producers. As patients prefer it, the
      cough plate merits further evaluation, particularly in non-sputum producers.

PMID- 15155408
TI  - Twelfth nerve palsy due to a retropharyngeal tuberculous abscess.

PMID- 15155411
TI  - The significance of a high plasma ammonia value.
AB  - At a tertiary referral centre, just over 50% of patients with plasma ammonia
      values over 200 micro mol/l had inborn errors of metabolism. To distinguish
      artefactual high values from those requiring treatment, the measurement should be
      repeated immediately if the result is above 200 micro mol/l and at lower
      concentrations if the patient is encephalopathic.

PMID- 15155409
TI  - Immunosuppressive therapy in acute myocarditis: an 18 year systematic review.
AB  - BACKGROUND: Immunosuppressive therapy is reportedly ineffective in adults with
      acute myocarditis. AIMS: To systematically review the impact of immunosuppressive
      therapy on the outcome of acute myocarditis in children. METHODS: A literature
      search for articles published from 1984 to 2003 was conducted with the following
      keywords: myocarditis, dilated cardiomyopathy, and immunosuppression. The
      relevant studies were systematically reviewed and comparison of treatment effect
      was made by calculating the odds ratio (OR) and confidence interval (CI) using
      the exact method based on the exact discrete reference distribution. RESULTS: Of
      the 1470 articles found, only nine studies were eligible. The odds for
      improvement with immunosuppression was between 4.33 (95% CI 0.52 to 52.23) and
      2.7 (95% CI 0.59 to 14.21). Addition of a second immunosuppressive agent to
      prednisolone only proved effective in one randomised controlled trial (OR 0.09,
      95% CI 0.01 to 0.52). Heterogeneity of these studies precluded pooled odds ratio.
      CONCLUSION: Current data suggest that immunosuppressive therapy does not
      significantly improve outcomes in children with acute myocarditis and there is
      insufficient evidence for its routine use. However, statistical power to detect a
      significant difference in the treatment effect may be limited because of the
      small number of subjects. This, together with problems of diagnosis, varying
      treatment practices, and a relative lack of evidence based guidelines would
      support efforts for a large multicentre, randomised controlled trial to better
      define the role of immunosuppression in acute myocarditis.

PMID- 15155412
TI  - My life with NF1.

PMID- 15155414
TI  - Bleeding ethics.

PMID- 15155415
TI  - Emergency asthma inhalers in schools.

PMID- 15155416
TI  - Men are from Mars...

PMID- 15155418
TI  - What is "inflammation"? Are we ready to move beyond Celsus?

PMID- 15155419
TI  - Exercise training: can it improve cardiovascular health in patients with type 2
      diabetes?

PMID- 15155420
TI  - Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a).
AB  - OBJECTIVES: To investigate the effects of two different regimens of androgenic
      anabolic steroid (AAS) administration on serum lipid and lipoproteins, and
      recovery of these variables after drug cessation, as indicators of the risk for
      cardiovascular disease in healthy male strength athletes. METHODS: In a non
      blinded study (study 1) serum lipoproteins and lipids were assessed in 19
      subjects who self administered AASs for eight or 14 weeks, and in 16 non-using
      volunteers. In a randomised double blind, placebo controlled design, the effects
      of intramuscular administration of nandrolone decanoate (200 mg/week) for eight
      weeks on the same variables in 16 bodybuilders were studied (study 2). Fasting
      serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL
      C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apolipoprotein A1 (Apo
      A1), apolipoprotein B (Apo-B), and lipoprotein (a) (Lp(a)) were determined.
      RESULTS: In study 1 AAS administration led to decreases in serum concentrations
      of HDL-C (from 1.08 (0.30) to 0.43 (0.22) mmol/l), HDL2-C (from 0.21 (0.18) to
      0.05 (0.03) mmol/l), HDL3-C (from 0.87 (0.24) to 0.40 (0.20) mmol/l, and Apo-A1
      (from 1.41 (0.27) to 0.71 (0.34) g/l), whereas Apo-B increased from 0.96 (0.13)
      to 1.32 (0.28) g/l. Serum Lp(a) declined from 189 (315) to 32 (63) U/l. Total
      cholesterol and triglycerides did not change significantly. Alterations after
      eight and 14 weeks of AAS administration were comparable. No changes occurred in
      the controls. Six weeks after AAS cessation, serum HDL-C, HDL2-C, Apo-A1, Apo-B,
      and Lp(a) had still not returned to baseline concentrations. Administration of
      AAS for 14 weeks was associated with slower recovery to pretreatment
      concentrations than administration for eight weeks. In study 2, nandrolone
      decanoate did not influence serum triglycerides, total cholesterol, HDL-C, HDL2
      C, HDL3-C, Apo-A1, and Apo-B concentrations after four and eight weeks of
      intervention, nor six weeks after withdrawal. However, Lp(a) concentrations
      decreased significantly from 103 (68) to 65 (44) U/l in the nandrolone decanoate
      group, and in the placebo group a smaller reduction from 245 (245) to 201 (194)
      U/l was observed. Six weeks after the intervention period, Lp(a) concentrations
      had returned to baseline values in both groups. CONCLUSIONS: Self administration
      of several AASs simultaneously for eight or 14 weeks produces comparable profound
      unfavourable effects on lipids and lipoproteins, leading to an increased
      atherogenic lipid profile, despite a beneficial effect on Lp(a) concentration.
      The changes persist after AAS withdrawal, and normalisation depends on the
      duration of the drug abuse. Eight weeks of administration of nandrolone decanoate
      does not affect lipid and lipoprotein concentrations, although it may selectively
      reduce Lp(a) concentrations. The effect of this on atherogenesis remains to be
      established.

PMID- 15155421
TI  - Salivary testosterone and cortisol in rugby players: correlation with
      psychological overtraining items.
AB  - BACKGROUND: A psychocomportemental questionnaire has been devised by the
      consensus group of the Societe Francaise de Medecine du Sport to characterise and
      quantify, using a list of functional and psychocomportemental signs, a state of
      "staleness", for which no biological indicator is unanimously recognised.
      OBJECTIVES: To determine the relation between this diagnostic method and two
      hormones (cortisol and testosterone) often used as indicators of a state of
      fitness or staleness. METHODS: The subjects were young rugby players. They were
      asked to complete the overtraining questionnaire and gave three saliva samples
      (at 8 am, 11 am, and 5 pm) during a rest day. Concentrations of cortisol and
      testosterone in the saliva were determined by radioimmunoassay. RESULTS: A
      preferential relation was found between the questionnaire score and testosterone
      concentration but not between the questionnaire score and cortisol concentration.
      CONCLUSIONS: The questionnaire may be a useful tool for screening subjects at
      risk of overtraining. Testosterone concentration is influenced by tiredness, and
      is therefore a valid marker of tiredness.

PMID- 15155423
TI  - Effect of trail design and grooming on the incidence of injuries at alpine ski
      areas.
AB  - OBJECTIVES: To identify the conditions at certain sites on slopes known as black
      spots for injury. METHOD: In the Hafjell and Voss alpine ski areas in Norway,
      1410 skiing injuries were recorded from December 1990 through the 1996 season. In
      Hafjell, 183 of these injuries were plotted on an area map during the two first
      seasons. Similarly, in Voss, 214 injuries were plotted on an area map for two
      seasons. During the last three seasons in Hafjell, 835 ski injuries were related
      to 6712 snow grooming hours and 6,829,084 lift journeys. RESULTS: The mean injury
      rate was 2.2 injuries per 1000 skier days, and the mean injury severity score
      (ISS) was 3.1. Accumulations of injuries at three sites (black spots) were
      recorded on the Hafjell area map. These injuries represented 40% of all injuries
      in the alpine area (p<0.05). Seven injury accumulation sites were recorded on the
      alpine area map of Voss, representing 22% of the total injuries (p>0.05).
      Grooming of the slopes was rated poor for the 49% of injuries that occurred at
      the sites of injury concentration and significantly different (27%) from injuries
      that occurred at random in Hafjell. The corresponding values in Voss were 50% and
      25% respectively. Grooming hours appeared to be inversely proportional to the
      number of injuries: R = -0.99 (p<0.02). The mean ISS declined significantly in
      Hafjell over the observation period (p<0.001). CONCLUSION: Inappropriate trail
      design and slope grooming seem to result in an accumulation of injuries at
      certain sites. Modification in construction and maintenance of the courses may
      reduce the number of injuries and mean ISS.

PMID- 15155424
TI  - Local corticosteroid injection in iliotibial band friction syndrome in runners: a
      randomised controlled trial.
AB  - OBJECTIVE: To establish whether a local injection of methylprednisolone acetate
      (40 mg) is effective in decreasing pain during running in runners with recent
      onset (less than two weeks) iliotibial band friction syndrome (ITBFS). METHODS:
      Eighteen runners with at least grade 2 ITBFS underwent baseline investigations
      including a treadmill running test during which pain was recorded on a visual
      analogue scale every minute. The runners were then randomly assigned to either
      the experimental (EXP; nine) or a placebo control (CON; nine) group. The EXP
      group was infiltrated in the area where the iliotibial band crosses the lateral
      femoral condyle with 40 mg methylprednisolone acetate mixed with a short acting
      local anaesthetic, and the CON group with short acting local anaesthetic only.
      The same laboratory based running test was repeated after seven and 14 days. The
      main measure of outcome was total pain during running (calculated as the area
      under the pain versus time graph for each running test). RESULTS: There was a
      tendency (p = 0.07) for a greater decrease in total pain (mean (SEM)) during the
      treadmill running in the EXP group than the CON group tests from day 0 (EXP = 222
      (71), CON = 197 (31)) to day 7 (EXP = 140 (87), CON = 178 (76)), but there was a
      significant decrease in total pain during running (p = 0.01) from day 7 (EXP =
      140 (87), CON = 178 (76)) to day 14 (EXP = 103 (89), CON = 157 (109)) in the EXP
      group compared with the CON group. CONCLUSION: Local corticosteroid infiltration
      effectively decreases pain during running in the first two weeks of treatment in
      patients with recent onset ITBFS.

PMID- 15155425
TI  - Statistical procedures for determining the extent of cognitive change following
      concussion.
AB  - Neuropsychological (NP) testing is now often used to help to determine if the
      cognitive function of a concussed athlete has declined. The NP test score after
      concussion is compared with the baseline test score. Many clinicians simply
      subtract one from the other and make a clinical decision about the significance
      or otherwise of the resulting "difference score". Such techniques are inadequate,
      as they fail to account for the many factors that may confound interpretation of
      serially acquired cognitive test scores. This is a review of a number of
      alternative approaches used in other areas of medicine for differentiating "true"
      changes from changes caused by these confounding factors. A case example is used
      to illustrate the effect that the statistical approach may have on clinical
      decision making.

PMID- 15155426
TI  - Subjective functional assessments and the return to competitive sport after
      anterior cruciate ligament reconstruction.
AB  - OBJECTIVES: To examine (a) return to competitive sport within 12 months of
      anterior cruciate ligament (ACL) reconstruction, (b) maintenance of competitive
      participation at follow up, and (c) the relation of the level of sports activity
      and competitive participation at follow up to subjective functional assessments.
      Also to address the incidence of continued competitive participation despite
      notable functional problems with the operated knee at 12 months and follow up.
      METHODS: All patients were competitive athletes before injury and had undergone
      ACL reconstruction by the transtibial endoscopic technique with either a bone
      patellar tendon-bone or a multiple looped hamstring autograft. Evaluation was
      carried out a mean of 43 months (range 24-73) after surgery by a postal
      questionnaire in which the Cincinnati sports activity scale (CSAS) and Cincinnati
      sports function scales were presented in conjunction with closed questions on
      change in competitive level and the presence of complaints. RESULTS: Of 109
      selected patients, 77 (71%) responded. At follow up, 62 of 77 patients (81%)
      reported that they had returned to competition within 12 months of surgery.
      Within the same time frame, 55 of the above 62 patients (89%) also claimed to
      have returned to the level at which they were competing before injury (or
      higher). At follow up, 30 of the above 55 patients (54%) reported to still be
      competing at this high level. Twelve of the above 55 patients (22%) also admitted
      to major problems with the operated knee at that time. The overall incidence of
      patients competing despite major functional impairment in the operated knee was
      13 of 62 (21%) at 12 months and six of 47 (13%) at follow up. Thirty eight
      patients (49%) were active in sport at least four times a week at follow up (CSAS
      level 1), and, using Spearman's rank correlation between CSAS scores and total
      sports function scores, r was calculated to be 0.44. Competitive and male
      patients had higher total sports function scores at follow up than non
      competitive (p = 0.005) and female (p = 0.02) patients respectively. CONCLUSIONS:
      The reported return to competition at the previous level, both within 12 months
      and at follow up, was high but as expected considering the standard of treatment,
      patient selection, and study exclusion criteria. Patients with few functional
      complaints maintained a high level of sporting activity, even after discontinuing
      competitive participation.

PMID- 15155427
TI  - Strong correlation of maximal squat strength with sprint performance and vertical
      jump height in elite soccer players.
AB  - BACKGROUND: A high level of strength is inherent in elite soccer play, but the
      relation between maximal strength and sprint and jumping performance has not been
      studied thoroughly. OBJECTIVE: To determine whether maximal strength correlates
      with sprint and vertical jump height in elite male soccer players. METHODS:
      Seventeen international male soccer players (mean (SD) age 25.8 (2.9) years,
      height 177.3 (4.1) cm, weight 76.5 (7.6) kg, and maximal oxygen uptake 65.7 (4.3)
      ml/kg/min) were tested for maximal strength in half squats and sprinting ability
      (0-30 m and 10 m shuttle run sprint) and vertical jumping height. RESULT: There
      was a strong correlation between maximal strength in half squats and sprint
      performance and jumping height. CONCLUSIONS: Maximal strength in half squats
      determines sprint performance and jumping height in high level soccer players.
      High squat strength did not imply reduced maximal oxygen consumption. Elite
      soccer players should focus on maximal strength training, with emphasis on
      maximal mobilisation of concentric movements, which may improve their sprinting
      and jumping performance.

PMID- 15155428
TI  - Validity of Queen's College step test for use with young Indian men.
AB  - OBJECTIVES: To assess the suitability of the Queen's College step test (QCT) to
      predict maximum oxygen uptake in Indian men. METHODS: Thirty sedentary male
      university students from West Bengal, India, with the same socioeconomic
      background and mean (SD) age, height, and weight of 22.6 (0.2) years, 166.4 (0.5)
      cm, and 53.8 (0.2) kg, respectively, were randomly sampled from University of
      Calcutta. VO2max of each participant was determined by direct procedure involving
      incremental bicycle exercise and also by applying indirect QCT method with a gap
      of 4 days between the tests. RESULTS: The difference between the mean (SD) VO2max
      values directly measured (VO2max = 39.8 (1.03) ml/min/kg body mass) and
      indirectly predicted (PVO2max = 39.3 (1.07) ml/min/kg body mass) was
      statistically insignificant (p>0.10). PVO2max and VO2max values expressed as
      ml/min/kg body mass corroborated with previous studies in the same laboratory
      involving the same population, and also exhibited significant statistical
      correlation (r = 0.95, p<0.001) between them. CONCLUSION: The results suggest
      that QCT can be applied in the studied population to produce a good estimation of
      maximum oxygen uptake, especially in the field where large numbers of
      participants are to be evaluated without a well equipped laboratory.

PMID- 15155430
TI  - Effects of prolonged strenuous exercise (marathon running) on biochemical and
      haematological markers used in the investigation of patients in the emergency
      department.
AB  - OBJECTIVES: To investigate the effects of strenuous exercise on commonly used
      biochemical and haematological variables in subjects running the 2002 London
      marathon. METHODS: 34 healthy volunteers (7 female, 27 male) were recruited for
      the study. Blood was taken before the start (at registration) and immediately
      after completion of the marathon. Samples were analysed for urea and
      electrolytes, liver function tests, creatine kinase (CK), CK-MB isoenzyme,
      myoglobin, troponin I, full blood count, a clotting screen, and D-dimers. The
      results before and after exercise were compared. Pearson's correlation
      coefficients were calculated for all variables. RESULTS: Significant increases
      were found in CK, CK-MB, aspartate aminotransferase (AST), lactate dehydrogenase
      (LDH), and myoglobin following the marathon. However, there was no significant
      change in the level of troponin I. There was also evidence of activation of the
      coagulation and fibrinolytic cascades following the marathon, with a reduction in
      activated partial thromboplastin time, a reduction in fibrinogen, and an increase
      in D-dimers. CONCLUSIONS: The results confirm previous individual studies on
      marathon running and the biochemical and haematological tests routinely carried
      out in hospital. These are affected by prolonged exercise, and "abnormal" results
      in these tests may be normal after prolonged exercise and therefore not
      diagnostic of a disease process. The results of investigations in patients who
      have been exercising should be interpreted with caution.

PMID- 15155432
TI  - Epidemiology of injuries in adventure racing athletes.
AB  - OBJECTIVES: To assess the demographics and training characteristics of adventure
      racing athletes in the United Kingdom, the prevalence and anatomical distribution
      of hazardous encounter, and overuse injury in this population, and the effects
      these injuries have on training. METHODS: A retrospective training and injury
      questionnaire for the previous 18 months was distributed to 300 adventure racing
      athletes at two national race meetings. The definition of an injury was "any
      musculoskeletal problem causing a stop in training for at least one day,
      reduction in training mileage, taking of medicine, or seeking of medical aid."
      RESULTS: The data were derived from the responses of 223 athletes. Advanced level
      athletes did 11 (4) sessions and 17 (8) hours of training a week (mean (SD)). An
      injury was reported in the previous 18 months by 73% of the respondents. The most
      common site of acute injury was the ankle (23%) and of chronic/overuse injury,
      the knee (30%), followed by the lower back, shin, and Achilles tendon (12% each).
      There were significant correlations (p<0.01) between the hours spent cycling per
      week and number of acute injuries, and between the number of days off per week
      and number of chronic/overuse injuries. Injuries resulted in an average of 23
      days training cessation or reduction. CONCLUSIONS: Acute injuries were sustained
      mainly as a result of the nature of the terrain over which athletes train and
      compete. In overuse injuries lack of adequate rest days was a significant
      contributing factor. Only a small proportion of training time was spent
      developing flexibility and core stability.

PMID- 15155431
TI  - Quadriceps atrophy: to what extent does it exist in patellofemoral pain syndrome?
AB  - BACKGROUND: Quadriceps atrophy is a commonly cited accompaniment to
      patellofemoral pain syndrome (PFPS), yet there is little valid, objective
      evidence for its existence. OBJECTIVE: To investigate atrophy and weakness of the
      quadriceps femoris muscle group in patients with PFPS using measures of cross
      sectional area and peak extension torque. METHODS: A total of 57 patients with
      insidious onset of PFPS and 10 healthy control subjects had ultrasound scanning
      of the quadriceps femoris. The scans were analysed using computerised planimetry
      to estimate the cross-sectional area of the quadriceps femoris. Lower limb peak
      torque was also measured using a Biodex dynamometer. RESULTS: The mean of %
      differences revealed a 3.38% (95% confidence interval (CI) 1.3 to 5.45)
      difference in cross-sectional area (CSA) between the affected and unaffected limb
      in PFPS patients and a 1.31% (95% CI 0.06 to 2.55) difference in the dominant and
      non-dominant limb of the control group; the between-groups difference was not
      significant (p = 0.409). There was a 18.4% (95% CI 13 to 23.8) difference between
      the affected and unaffected limb in peak torque in PFPS patients and a 7.6% (95%
      CI 3.2 to 12) difference between the dominant and non-dominant limb in the
      control group; the between-groups difference was significant (p = 0.002).
      CONCLUSIONS: The mean of % differences of 3.38% quadriceps atrophy between limbs
      was considerably less than the only other study using ultrasound scanning on the
      quadriceps in PFPS and was not significant between the groups. There were greater
      and more significant between-group differences in lower limb peak torque
      indicating that muscle strength may not be related to muscle size. These results
      help to re-appraise of the amount of quadriceps atrophy in PFPS.

PMID- 15155434
TI  - Quantitative sports and functional classification (QSFC) for disabled people with
      spasticity.
AB  - Although sports classification for cerebral palsy has been in use for several
      years, it is complicated both for training and for scoring. People with cerebral
      palsy are difficult to fit into classification systems that are appropriate for
      other disability groups. The aim of this report is to describe the development of
      a framework for a simple quantitative classification of cerebral palsy. It was
      designed to be easily understood by all who are investigating, treating,
      training, coaching, and working with spastic disabled people. The scoring system
      is accurate and quick, so long as the definitions of items listed are adhered to.

PMID- 15155433
TI  - Role of a mixed type, moderate intensity exercise programme after peripheral
      blood stem cell transplantation.
AB  - OBJECTIVES: To evaluate the effect of peripheral blood stem cell transplantation
      on functional capacity, and to determine the role of a mixed type, moderate
      intensity exercise programme in the recovery of patients after intensive cancer
      treatment. METHODS: Peak aerobic capacity and muscular strength (upper body,
      lower body, and handgrip strength) measures were assessed before (PI) and after
      (PII) transplant and after a 12 week intervention period (PIII). After PII, 12
      patients aged 16-64 years were allotted in equal numbers to a control group or
      exercise intervention group. RESULTS: Mean peak aerobic capacity and muscular
      strength were reduced after the transplant, with significant (p<0.05) decreases
      for upper body strength. No change was found in aerobic capacity and muscular
      strength between PII and PIII for the control group. In contrast, participation
      in the exercise programme led to significant improvements in peak aerobic
      capacity (p<0.05) and upper and lower body strength (p<0.01). In addition, values
      recorded after the three month intervention period were significantly higher than
      before treatment for peak aerobic capacity (litres/min (p<0.05) and ml/kg/min
      (p<0.01)) and lower body strength (p<0.01). CONCLUSION: Intensive treatment for
      cancer can adversely affect aerobic capacity and muscular strength. A mixed type,
      moderate intensity exercise programme can help patients to regain fitness and
      strength within three months. No exercise can exacerbate physical losses
      resulting from treatment.

PMID- 15155435
TI  - The management of facial injuries in rugby union.
AB  - BACKGROUND: There are as yet no guidelines in rugby union for the management of
      facial lacerations which account for one-third of total injuries sustained by
      players. METHOD: We devised a questionnaire to establish the current standards in
      rugby union clubs in England. The questionnaire covered such issues as inadequate
      wound cleansing, inappropriate suture material, the use of sterile suture
      equipment, and advice required for suture removal. RESULTS: We recommend that a
      dedicated medical room should be available in all clubs, the doctor should always
      wear gloves, and local anaesthetic and sterile suture packs and instruments
      should be provided.

PMID- 15155436
TI  - Diclofenac patch for topical treatment of acute impact injuries: a randomised,
      double blind, placebo controlled, multicentre study.
AB  - OBJECTIVES: To investigate the clinical efficacy and safety of a newly developed
      diclofenac patch in the topical treatment of blunt impact injuries. METHODS: This
      was a randomised, placebo controlled, double blind, multicentre study in 120
      patients with traumatic blunt soft tissue injury. Within 3 h of the injury
      participants of sport competitions and training camps were enrolled and treated
      twice daily with the diclofenac or a placebo patch over a period of 7 days.
      Patients were randomised (1:1) to two parallel groups. Tenderness produced by
      pressure was measured twice daily during the first 3 days after enrollment as
      well as at day 7. Tenderness was defined as the amount of pressure (measured by a
      calibrated caliper at the centre of the injury) that first produced a pain
      reaction as reported by the patient. RESULTS: The primary efficacy variable was
      the area under the curve for tenderness over the first 3 days. The diclofenac
      patch was significantly more effective than placebo (p<0.0001). The treatment
      effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between
      diclofenac and placebo patches. These results were supported by all secondary
      efficacy variables. The diclofenac patch produced rapid pain relief as reflected
      by the time to reach resolution of pain at the injured site which was
      significantly shorter compared to placebo (p<0.0001). The diclofenac patch was
      well tolerated. The most frequently observed adverse events were local cutaneous
      adverse reactions (pruritus, rash) of minor severity occurring with the same
      frequency as in the placebo group. CONCLUSIONS: A newly developed diclofenac
      patch is effective and safe for the treatment of blunt impact injuries.

PMID- 15155437
TI  - Effects of 20 days of bed rest on the viscoelastic properties of tendon
      structures in lower limb muscles.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of 20 days'
      bed rest on the viscoelastic properties of human tendon structures in knee
      extensor and plantar flexor muscles in vivo. METHODS: Eight healthy men (age:
      24+/-4 years, height: 172+/-9 m, body mass: 69+/-13 kg) carried out a 6 degrees
      head-down bed rest for 20 days. Before and after bed rest, elongation (L) of the
      tendon and aponeurosis of vastus lateralis (VL) and medial gastrocnemius muscles
      (MG) during isometric knee extension and plantar flexion, respectively, were
      determined using real-time ultrasonic apparatus, while the subjects performed
      ramp isometric contraction up to the voluntary maximum, followed by ramp
      relaxation. The relationship between estimated muscle force (Fm) and tendon
      elongation (L) was fitted to a linear regression, the slope of which was defined
      as stiffness. The hysteresis was calculated as the ratio of the area within the
      Fm-L loop to the area beneath the load portion of the curve. RESULTS: L values
      above 100 N were significantly greater after bed rest for VL, while there were no
      significant differences in L values between before and after for MG. The
      stiffness decreased after bed rest for VL (70.3+/-27.4 v 50.1+/-24.8 N/mm, before
      and after bed rest, respectively; p = 0.003) and MG (29.4+/-7.5 v 25.6+/-7.8
      N/mm, before and after bed rest, respectively; p = 0.054). In addition,
      hysteresis increased after bed rest for VL (16.5+/-7.1% v 28.2+/-12.9%, before
      and after bed rest, respectively; p = 0.017), but not for MG (17.4+/-4.4% v
      17.7+/-6.1%, before and after bed rest, respectively; p = 0.925). CONCLUSIONS:
      These results suggested that bed rest decreased the stiffness of human tendon
      structures and increased their hysteresis, and that these changes were found in
      knee extensors, but not the plantar flexors.

PMID- 15155438
TI  - Do physical leisure time activities prevent fatigue? A 15 month prospective study
      of nurses' aides.
AB  - OBJECTIVE: To test the hypothesis that physical leisure time activities reduce
      the risk of developing persistent fatigue. METHODS: The hypothesis was tested in
      a sample that was homogeneous with respect to sex and occupation, with a
      prospective cohort design. Of 6234 vocationally active, female, Norwegian nurses'
      aides, not on leave because of illness or pregnancy when they completed a mailed
      questionnaire in 1999, 5341 (85.7%) completed a second questionnaire 15 months
      later. The main outcome measure was the prevalence of persistent fatigue-that is,
      always or usually feeling fatigued in the daytime during the preceding 14 days.
      RESULTS: In participants without persistent fatigue at baseline, reported
      engagement in physical leisure time activities for 20 minutes or more at least
      once a week during the three months before baseline was associated with a reduced
      risk of persistent fatigue at the follow up (odds ratio = 0.70; 95% confidence
      interval 0.55 to 0.89), after adjustments for age, affective symptoms, sleeping
      problems, musculoskeletal pain, long term health problems of any kind, smoking,
      marital status, tasks of a caring nature during leisure time, and work factors at
      baseline. CONCLUSION: The study supports the hypothesis that physical leisure
      time activities reduce the risk of developing persistent fatigue.

PMID- 15155439
TI  - Extreme risk taker who wants to continue taking part in high risk sports after
      serious injury.
AB  - The case is reported of a 40 year old male high risk sport athlete who had
      seriously injured himself several times and as a result was partially physically
      disabled and had trouble with mental tasks requiring concentration such as
      spelling, reading numbers, and writing. The athlete was referred to a sports
      psychologist. In consultations, it became clear that he was having difficulty
      reconciling the difference between his life as it used to be and as it would be
      in the future. Part of his difficulty was dealing with the frustration and anger
      "outbursts" which resulted from not being able to perform straightforward
      everyday motor skills. In spite of his injuries and disability, the patient badly
      wanted to continue participating in extreme sports. Reversal theory is used in
      the discussion to provide theoretical explanations of the motivation for his
      extreme risk taking behaviour.

PMID- 15155440
TI  - Mountain bike injuries and clipless pedals: a review of three cases.
AB  - The cases are reported of three off road cyclists with isolated soft tissue
      injuries to the right lower leg, caused by the chain ring as they struggled to
      release their feet from clipless pedals. Correct adjustment of the pedals to
      facilitate quick release of the feet is required to prevent such injuries.

PMID- 15155441
TI  - Closed posteromedial dislocation of the tibiotalar joint without fracture in a
      basketball player.
AB  - Acute ankle injury is one of the most common problems in sports medicine.
      Although most are ankle sprains, dislocations are occasionally seen. The case is
      presented of a closed posteromedial ankle dislocation without fracture which
      occurred during a basketball match. The literature is also reviewed.

PMID- 15155442
TI  - Mountaineer's heel.
AB  - Mountaineers are at risk of skin lesions caused by constant boot friction. This
      is the case of a 35 year old mountaineer who presented with large and deeply
      ulcerated lesions over the medial aspects of both heels after a two and a half
      day climb using crampons. A number of factors such as the length of the climb in
      cold and thin air and the impossibility of removal of the footwear to allow rapid
      rewarming may have contributed to a more acute presentation of these lesions.

PMID- 15155443
TI  - Intramuscular haemangioma of the thigh in a basketball player.
AB  - Haemangioma is a common benign soft tissue tumour. Intramuscular haemangiomas may
      present as a perceived sporting injury. Magnetic resonance imaging is the
      investigation of choice. Intramuscular haemangioma should be considered in the
      differential diagnosis of unexplained pain and swelling in a muscle.

PMID- 15155444
TI  - Effect of massage of the hamstring muscle group on performance of the sit and
      reach test.
AB  - OBJECTIVE: To investigate if a single massage of the hamstring muscle group would
      alter the performance of the sit and reach test. METHODS: Before treatment, each
      of 11 male subjects performed the sit and reach test. The treatment consisted of
      either massage of the hamstring muscle group (both legs, total time about 15
      minutes) or supine rest with no massage. Performance of the sit and reach test
      was repeated after treatment. Each subject returned the subsequent week to
      perform the tests again, receiving the alternative treatment relative to their
      initial visit. Mean percentage changes in sit and reach scores after treatment
      were calculated for the massage and no massage treatments, and analysed using
      Student's t tests. RESULTS: Mean (SD) percentage changes in sit and reach scores
      after massage and no massage were small (6.0 (4.3)% and 4.6 (4.8)% respectively)
      and not significantly different for subjects with relatively high (15 cm and
      above) values before treatment. Mean percentage changes in sit and reach scores
      for subjects with relatively low values before treatment (below 15 cm) were large
      (18.2 (8.2)% and 15.5 (16.2)% respectively), but no significant differences were
      found between the massage and no massage groups. CONCLUSIONS: A single massage of
      the hamstring muscle group was not associated with any significant increase in
      sit and reach performance immediately after treatment in physically active young
      men.

PMID- 15155445
TI  - Treatment of spondylolysis with external electrical stimulation in young
      athletes: a critical literature review.
AB  - Lumbar spondylolysis is a common cause of low back pain in adolescent athletes.
      It is a unilateral or bilateral defect of the pars interarticularis. The cause is
      still a matter of debate. A wide range of conservative treatments has been used.
      The purpose of this critical literature review is to investigate the efficacy of
      external electrical stimulation in the healing of this disorder.

PMID- 15155446
TI  - Physiology of sport rock climbing.
AB  - Rock climbing has increased in popularity as both a recreational physical
      activity and a competitive sport. Climbing is physiologically unique in requiring
      sustained and intermittent isometric forearm muscle contractions for upward
      propulsion. The determinants of climbing performance are not clear but may be
      attributed to trainable variables rather than specific anthropometric
      characteristics.

PMID- 15155447
TI  - The obesity epidemic: too much food for thought?
AB  - Traditional treatment strategies and public health interventions aimed at
      reducing the incidence of obesity are proving inadequate at controlling the
      global epidemic of this condition. The main focus of any intervention should be
      on preventing small excesses of weight, which lead to large weight gain over
      time, as once a large amount of excess weight is gained, it is very difficult to
      lose. The only effective approach is for governments to implement radical policy
      change, to regulate food consumption and control the food industry in a similar
      way to that of the tobacco industry, by banning the advertising of selected
      produce, taxing certain foods, and rationing the purchase of others.

PMID- 15155448
TI  - Complex regional pain syndrome in thoracic outlet syndrome.

PMID- 15155449
TI  - Upper body contribution to high intensity cycle ergometer exercise: implications
      for blood lactate measurements and power profiles.

PMID- 15155450
TI  - Mandatory wearing of helmets for elite cyclists: new perspectives in prevention
      of head injuries.

PMID- 15155451
TI  - Clinical governance is unworkable.

PMID- 15155454
TI  - A punch drunk jockey?
AB  - The case is reported of a retired professional jockey with progressive memory
      loss. The concern is that he may be suffering from chronic traumatic
      encephalopathy or the "punch drunk syndrome".

PMID- 15155455
TI  - Recurrent macroscopic haematuria due to bladder blood vessels after exercise
      induced haematuria.
AB  - The case is reported of exercise induced asymptomatic macroscopic haematuria,
      which became recurrent haematuria no longer induced by exercise. The cause,
      diagnosis, and management are discussed. An overview of the potential causes of
      sport related haematuria is presented.

PMID- 15155456
TI  - Isolated first rib fracture in athletes.
AB  - Isolated fractures of the first rib are uncommon. They are caused by major blunt
      trauma, a violent muscular pull, or fatigue. Diagnosis is usually made by chest
      radiography and computed tomography. Angiography is justified when certain
      criteria are met. Treatment is rest and mild analgesia. Early and late
      complications have been reported and are treated accordingly. The purpose of this
      article is to report a case of first rib stress fracture in a kick boxer and
      review the pertinent literature.

PMID- 15155453
TI  - What do we mean by the term "inflammation"? A contemporary basic science update
      for sports medicine.
AB  - Most practicing sports medicine clinicians refer to the concept of "inflammation"
      many times a day when diagnosing and treating acute and overuse injuries. What is
      meant by this term? Is it a "good" or a "bad" process? The major advances in the
      understanding of inflammation in recent years are summarised, and some clinical
      implications of the contemporary model of inflammation are highlighted.

PMID- 15155458
TI  - HTLV-I Tax induces a novel interaction between p65/RelA and p53 that results in
      inhibition of p53 transcriptional activity.
AB  - Nuclear factor kappaB (NF-kappaB) activation plays a critical role in oncogenesis
      by human T-cell lymphotrophic virus type I (HTLV-I), the etiologic agent of adult
      T-cell leukemia (ATL), and is indispensable for maintenance of the malignant
      phenotype. In T lymphocytes, Tax-mediated p53 inhibition is dependent on Tax
      activation of the NF-kappaB pathway and is linked to p53 phosphorylation. We now
      report that blocking NF-kappaB transcriptional activation in HTLV-I-transformed
      cells restores p53 activity. Further, using mouse embryo fibroblast (MEF) null
      cells and antisense oligonucleotides to inhibit expression of NF-kappaB family
      members, we demonstrate that the p65 subunit of NF-kappaB is uniquely involved in
      p53 inhibition. Coimmunoprecipitation assays demonstrate an interaction between
      p65 and p53 in HTLV-I-transformed cells. In transient transfection assays, we
      demonstrate that Tax induces the p53-p65 interaction. Phosphorylation of p53 at
      serines 15 and 392 is critical for complex formation. Importantly, Tax-mediated
      p53 inhibition correlates with p65 and p53 interaction. By using chromatin
      immunoprecipitation (ChIP) assays, we find that in HTLV-I-transformed cells p53
      and p65 form a complex on the inactive, p53-responsive murine double minute 2
      (MDM2) promoter. Consistent with reduced transcriptional activity, transcription
      factor IID (TFIID) binding is not observed. These studies identify a unique
      mechanism for p53 regulation by the p65/RelA subunit of NF-kappaB.

PMID- 15155457
TI  - Nontransferrin-bound iron uptake by hepatocytes is increased in the Hfe knockout
      mouse model of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is an iron-overload disorder caused by a C282Y
      mutation in the HFE gene. In HH, plasma nontransferrin-bound iron (NTBI) levels
      are increased and NTBI is bound mainly by citrate. The aim of this study was to
      examine the importance of NTBI in the pathogenesis of hepatic iron loading in Hfe
      knockout mice. Plasma NTBI levels were increased 2.5-fold in Hfe knockout mice
      compared with control mice. Total ferric citrate uptake by hepatocytes isolated
      from Hfe knockout mice (34.1 +/- 2.8 pmol Fe/mg protein/min) increased by 2-fold
      compared with control mice (17.8 +/- 2.7 pmol Fe/mg protein/min; P <.001; mean +/
      SEM; n = 7). Ferrous ion chelators, bathophenanthroline disulfonate, and 2',2
      bipyridine inhibited ferric citrate uptake by hepatocytes from both mouse types.
      Divalent metal ions inhibited ferric citrate uptake by hepatocytes, as did
      diferric transferrin. Divalent metal transporter 1 (DMT1) mRNA and protein
      expression was increased approximately 2-fold by hepatocytes from Hfe knockout
      mice. We conclude that NTBI uptake by hepatocytes from Hfe knockout mice
      contributed to hepatic iron loading. Ferric ion was reduced to ferrous ion and
      taken up by hepatocytes by a pathway shared with diferric transferrin. Inhibition
      of uptake by divalent metals and up-regulation of DMT1 expression suggested that
      NTBI uptake was mediated by DMT1.

PMID- 15155459
TI  - Chromosomal localization, hematologic characterization, and iron metabolism of
      the hereditary erythroblastic anemia (hea) mutant mouse.
AB  - Understanding iron metabolism has been enhanced by identification of genes for
      iron deficiency mouse mutants. We characterized the genetics and iron metabolism
      of the severe anemia mutant hea (hereditary erythroblastic anemia), which is
      lethal at 5 to 7 days. The hea mutation results in reduced red blood cell number,
      hematocrit, and hemoglobin. The hea mice also have elevated Zn protoporphyrin and
      serum iron. Blood smears from hea mice are abnormal with elevated numbers of
      smudge cells. Aspects of the hea anemia can be transferred by hematopoietic stem
      cell transplantation. Neonatal hea mice show a similar hematologic phenotype to
      the flaky skin (fsn) mutant. We mapped the hea gene near the fsn locus on mouse
      chromosome 17 and show that the mutants are allelic. Both tissue iron overloading
      and elevated serum iron are also found in hea and fsn neonates. There is a shift
      from iron overloading to iron deficiency as fsn mice age. The fsn anemia is cured
      by an iron-supplemented diet, suggesting an iron utilization defect. When this
      diet is removed there is reversion to anemia with concomitant loss of overloaded
      iron stores. We speculate that the hea/fsn gene is required for iron uptake into
      erythropoietic cells and for kidney iron reabsorption.

PMID- 15155460
TI  - Improvement in quality of life of patients with AL amyloidosis treated with high
      dose melphalan and autologous stem cell transplantation.
AB  - Treatment of AL amyloidosis patients with high-dose melphalan chemotherapy
      followed by autologous peripheral blood stem cell transplantation (HDM/SCT) can
      produce hematologic complete responses (CRs) and improvement in organ function.
      To determine whether these responses are accompanied by improvement in quality of
      life (QOL), we employed the Medical Outcomes Study (MOS) 36-item Short Form
      General Health Survey (SF-36) questionnaire for 544 patients evaluated between
      1994 and 2002. At baseline, the scores were significantly lower on all 8 SF-36
      scales compared with age-matched population norms: the composite physical
      component summary (PCS) for the AL patients was 34.5 versus the population norm
      of 46.8, and the mental component summary (MCS) was 45.0 versus the norm of 51.5.
      All SF-36 scores improved at 1 year, with the MCS reaching the population norm.
      The PCS, though improved, was still lower than normal but was greater in the
      subgroup of patients who achieved a hematologic CR; the PCS normalized at 2 years
      in these patients. Thus, treatment of AL amyloidosis patients with HDM/SCT
      produces measurable and sustained improvements in quality of life, particularly
      in those patients who achieve hematologic CR.

PMID- 15155461
TI  - A dose effect of IL-7 on thymocyte development.
AB  - To study interleukin-7 (IL-7) in early thymocyte development, we generated mice
      transgenic (Tg) for the IL-7 gene under control of the lck proximal promoter.
      Founder line TgA, with the lowest level of IL-7 overexpression, showed enhanced
      alphabeta T-cell development. In contrast, in the highest overexpressing founder
      line, TgB, alphabeta T-cell development was disturbed with a block at the
      earliest intrathymic precursor stage. This was due to decreased progenitor
      proliferation as assessed by Ki-67 staining and in vivo bromodeoxyuridine (BrdU)
      incorporation. Bcl-2 was up-regulated in T-cell-committed progenitors in all Tg
      lines, and accounted for greater numbers of double positive (DP), CD4 single
      positive (SP), and CD8SP thymocytes in TgA mice where, in contrast to TgB mice,
      thymocyte progenitor proliferation was normal. Mixed marrow chimeras using TgB(+)
      and congenic mice as donors, and experiments using anti-IL-7 monoclonal antibody
      (MAb) in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype.
      In conclusion, at low Tg overexpression, IL-7 enhanced alphabeta T-cell
      development by increasing thymocyte progenitor survival, while at high
      overexpression IL-7 reduces their proliferation, inducing a dramatic block in DP
      production. These results show for the first time in vivo a dose effect of IL-7
      on alphabeta T-cell development and have implications for IL-7 in the clinical
      setting.

PMID- 15155463
TI  - Cell-intrinsic requirement for pRb in erythropoiesis.
AB  - Retinoblastoma (Rb) and family members have been implicated as key regulators of
      cell proliferation and differentiation. In particular, accumulated data have
      suggested that the Rb gene product pRb is an important controller of erythroid
      differentiation. However, current published data are conflicting as to whether
      the role of pRb in erythroid cells is cell intrinsic or non-cell intrinsic. Here,
      we have made use of an in vitro erythroid differentiation culture system to
      determine the cell-intrinsic requirement for pRb in erythroid differentiation. We
      demonstrate that the loss of pRb function in primary differentiating erythroid
      cells results in impaired cell cycle exit and terminal differentiation.
      Furthermore, we have used coculture experiments to establish that this
      requirement is cell intrinsic. Together, these data unequivocally demonstrate
      that pRb is required in a cell-intrinsic manner for erythroid differentiation and
      provide clarification as to its role in erythropoiesis.

PMID- 15155464
TI  - Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in
      iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator.
AB  - Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated
      with tissue iron overload and toxicity. We characterized NTBI's susceptibility to
      deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma
      iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment
      of patients with hemoglobin E disease and beta-thalassemia (n = 17). In 97% of
      serum samples (n = 267), the LPI levels were more than 0.4 microM (mean +/- SEM,
      3.1 +/- 0.2 microM) and the percent transferrin (Tf) saturation more than 85 (111
      +/- 6), whereas only in 4% of sera were the LPI levels more than 0.4 microM for
      Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17
      months caused both LPI and DCI to decrease from respective initial 5.1 +/- 0.5
      and 5.4 +/- 0.6 microM to steady mean levels of 2.18 +/- 0.24 and 2.81 +/- 0.14
      microM. The steady lowest levels of LPI and DCI were attained after 6 to 8
      months, with a half time (t(1/2)) of 2 to 3 months. Serum ferritin and red cell
      membrane-associated iron followed a similar course but attained steady basal
      levels only after 10 to 12 months of continuous treatment, with a t(1/2) of 5 to
      7 months. These studies indicate that LPI and DCI can serve as early indicators
      of iron overload and as measures for the effectiveness of iron chelation in
      reducing potentially toxic iron in the plasma.

PMID- 15155462
TI  - Genomic approaches to hematologic malignancies.
AB  - In the past several years, experiments using DNA microarrays have contributed to
      an increasingly refined molecular taxonomy of hematologic malignancies. In
      addition to the characterization of molecular profiles for known diagnostic
      classifications, studies have defined patterns of gene expression corresponding
      to specific molecular abnormalities, oncologic phenotypes, and clinical outcomes.
      Furthermore, novel subclasses with distinct molecular profiles and clinical
      behaviors have been identified. In some cases, specific cellular pathways have
      been highlighted that can be therapeutically targeted. The findings of microarray
      studies are beginning to enter clinical practice as novel diagnostic tests, and
      clinical trials are ongoing in which therapeutic agents are being used to target
      pathways that were identified by gene expression profiling. While the technology
      of DNA microarrays is becoming well established, genome-wide surveys of gene
      expression generate large data sets that can easily lead to spurious conclusions.
      Many challenges remain in the statistical interpretation of gene expression data
      and the biologic validation of findings. As data accumulate and analyses become
      more sophisticated, genomic technologies offer the potential to generate
      increasingly sophisticated insights into the complex molecular circuitry of
      hematologic malignancies. This review summarizes the current state of discovery
      and addresses key areas for future research.

PMID- 15155465
TI  - Molecular and cellular mechanisms underlying iron transport deficiency in
      microcytic anemia.
AB  - A mutation of the iron transporter Nramp2 (DMT1, Slc11a2) causes microcytic
      anemia in mk mice and in Belgrade rats by impairing iron absorption in the
      duodenum and in erythroid cells, causing severe iron deficiency. Both mk and
      Belgrade animals display a glycine-to-arginine substitution at position 185
      (G185R) in the fourth predicted transmembrane domain of Nramp2. To study the
      molecular basis for the loss of function of Nramp2(G185R), we established cell
      lines stably expressing extracellularly tagged versions of wild-type (WT) or
      mutated transporters. Like WT Nramp2, the G185R mutant was able to reach the
      plasmalemma and endosomal compartments, but with reduced efficiency. Instead, a
      large fraction of Nramp2(G185R) was detected in the endoplasmic reticulum, where
      it was unstable and was rapidly degraded by a proteasome-dependent mechanism.
      Moreover, the stability of the mutant protein that reached the plasma membrane
      was greatly reduced, further diminishing its surface density at steady state.
      Last, the specific metal transport activity of plasmalemmal Nramp2(G185R) was
      found to be significantly depressed, compared with its WT counterpart. Thus, a
      singlepoint mutation results in multiple biosynthetic and functional defects that
      combine to produce the impaired iron deficiency that results in microcytic
      anemia.

PMID- 15155466
TI  - Treatment of myelodysplastic syndromes with valproic acid alone or in combination
      with all-trans retinoic acid.
AB  - Valproic acid (VPA) has been shown to inhibit histone deacetylase activity and to
      synergize with all-trans retinoic acid (ATRA) in the differentiation induction of
      acute myelogenous leukemia (AML) blasts in vitro. We treated 18 patients with
      myelodysplastic syndromes (MDS) and AML secondary to MDS (sAML/MDS) with VPA
      monotherapy (serum concentrations 346-693 microM [50-100 microg/mL]). Five
      patients received VPA and ATRA (80 mg/m(2)/d, days 1-7, every other week).
      Response according to international working group (IWG) criteria was observed in
      8 patients (44%) on VPA monotherapy, including 1 partial remission. Median
      response duration was 4 months (range, 3-9 months). Four of 5 patients relapsing
      were treated with VPA + ATRA, 2 of them responding again. Among 5 patients
      receiving VPA + ATRA from the start, none responded according to IWG criteria,
      but 1 patient with sAML/MDS achieved a marked reduction in peripheral and marrow
      blasts. Thus, VPA is of therapeutic benefit for patients with MDS, and ATRA may
      be effective when added later.

PMID- 15155467
TI  - CD19-targeting liposomes containing imatinib efficiently kill Philadelphia
      chromosome-positive acute lymphoblastic leukemia cells.
AB  - Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
      (Ph(+) ALL) have poor prognosis despite intensive therapeutic intervention.
      Recently, imatinib, a BCR-ABL tyrosine kinase inhibitor, has been proven to be an
      effective treatment for Ph(+) ALL, but nearly all patients rapidly acquire
      resistance. High-dose imatinib administration might overcome this resistance;
      however, systemic toxicities would likely limit this approach. Therefore, a new
      delivery system allowing for the specific targeting of imatinib is urgently
      needed. Because almost all Ph(+) ALL cells express CD19 on their surface, we have
      developed an immunoliposome carrying anti-CD19 antibody (CD19-liposomes). The
      internalization efficiency of the CD19-liposomes approached 100% in all Ph(+) ALL
      cells but was very low in CD19(-) cells. The cytocidal effect of imatinib
      encapsulated CD19-liposomes (imatinib-CD19-liposomes) on Ph(+) ALL cell lines and
      primary leukemia cells from patients with Ph(+) ALL was much greater than that of
      imatinib with or without control liposomes. Importantly, the imatinib-CD19
      liposomes did not affect the colony formation of CD34(+) hematopoietic cells,
      even at inhibitory concentration of free imatinib. Taken together, these data
      clearly demonstrate that the imatinib-CD19-liposomes induced specific and
      efficient death of Ph(+) ALL cells. This new therapeutic approach might be a
      useful treatment for Ph(+) ALL with fewer side effects than free imatinib.

PMID- 15155468
TI  - OSCAR is an FcRgamma-associated receptor that is expressed by myeloid cells and
      is involved in antigen presentation and activation of human dendritic cells.
AB  - We have isolated a novel cell surface molecule, the human homolog of osteoclast
      associated receptor (OSCAR). Unlike mouse OSCAR, hOSCAR is widely transcribed in
      cells of the myeloid lineage. Notably, hOSCAR is expressed on circulating blood
      monocytes and CD11c(+) dendritic cells but not on T and B cells. hOSCAR is
      continually expressed during differentiation of CD14(+) monocytes into dendritic
      cells and maintained after maturation. hOSCAR associates with the FcRgamma as
      shown by translocation of FcRgamma to the cell surface in presence of hOSCAR and
      coimmunoprecipitation from transfected cell lines and ex vivo cells. Engagement
      of hOSCAR with specific mAb leads to Ca(2+) mobilization and cytokine release,
      indicators of cellular activation. Endocytosis of the receptor in dendritic cells
      was observed, followed by passage of the internalized material into Lamp-1(+) and
      HLA-DR(+) compartments, suggesting a role in antigen uptake and presentation.
      Dendritic cells were able to stimulate a T-cell clone specific for an epitope of
      mouse IgG1 after uptake and processing of the hOSCAR-specific antibody,
      demonstrating the capacity of this receptor to mediate antigen presentation.
      hOSCAR thus represents a novel class of molecule expressed by dendritic cells
      involved in the initiation of the immune response.

PMID- 15155469
TI  - Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case
      control study.

PMID- 15155470
TI  - Hospital discharge rates for suspected acute coronary syndromes between 1990 and
      2000: population based analysis.

PMID- 15155471
TI  - Failure of cidofovir in HIV-associated multicentric Castleman disease.

PMID- 15155472
TI  - Only genuine CD4+CD25+ Tregs may be friends or foes.

PMID- 15155473
TI  - On the roles of cGMP and glycoprotein Ib in platelet activation.

PMID- 15155474
TI  - Irreversible myelosuppression after fludarabine-melphalan conditioning:
      observations in patients with graft rejection.

PMID- 15155475
TI  - Disclosure of sexual preferences and lesbian, gay, and bisexual practitioners.

PMID- 15155476
TI  - Another threat to research in the United Kingdom.

PMID- 15155477
TI  - Affirmative action: the lessons for health care.

PMID- 15155478
TI  - Vulval vestibulitis.

PMID- 15155479
TI  - Inhaled insulin.

PMID- 15155480
TI  - Pfizer pleads guilty, but drug sales continue to soar.

PMID- 15155483
TI  - Report warns of continuing violations of code on breast milk substitute
      marketing.

PMID- 15155484
TI  - FDA rejects over the counter status for emergency contraceptive.

PMID- 15155485
TI  - Court dismisses appeals of two mothers.

PMID- 15155487
TI  - Spending on neglected diseases has increased, says report.

PMID- 15155490
TI  - Tobacco campaigners worried by slow progress on convention.

PMID- 15155492
TI  - Fourteen cases of euthanasia to be referred to French police.

PMID- 15155493
TI  - Move to sell statins over the counter raises concerns.

PMID- 15155494
TI  - New York's war on tobacco produces record fall in smoking.

PMID- 15155496
TI  - Breaches of safety regulations are probable cause of recent SARS outbreak, WHO
      says.

PMID- 15155495
TI  - One hospitality worker a week dies from passive smoking, study shows.

PMID- 15155498
TI  - Russia to raise tax rate for unfiltered cigarettes by 30%.

PMID- 15155499
TI  - Obstetricians at Lisbon hospital go on strike.

PMID- 15155501
TI  - Substance misuse and violent crime: Swedish population study.

PMID- 15155502
TI  - Review of instruments for peer assessment of physicians.
AB  - OBJECTIVES: To identify existing instruments for rating peers (professional
      colleagues) in medical practice and to evaluate them in terms of how they have
      been developed, their validity and reliability, and their appropriateness for use
      in clinical settings, including primary care. DESIGN: Systematic literature
      review. DATA SOURCES: Electronic search techniques, snowball sampling, and
      correspondence with specialists. STUDY SELECTION: The peer assessment instruments
      identified were evaluated in terms of how they were developed and to what extent,
      if relevant, their psychometric properties had been determined. RESULTS: A search
      of six electronic databases identified 4566 possible articles. After appraisal of
      the abstracts and in depth assessment of 42 articles, three rating scales
      fulfilled the inclusion criteria and were fully appraised. The three instruments
      did not meet established standards of instrument development, as no reference was
      made to a theoretical framework and the published psychometric data omitted
      essential work on construct and criterion validity. Rater training was absent,
      and guidance consisted of short written instructions. Two instruments were
      developed for a hospital setting in the United States and one for a primary care
      setting in Canada. CONCLUSIONS: The instruments developed to date for physicians
      to evaluate characteristics of colleagues need further assessment of validity
      before their widespread use is merited.

PMID- 15155503
TI  - "Soft" assessment--an oxymoron?

PMID- 15155505
TI  - RNA interference.

PMID- 15155506
TI  - Pacemaker induced ventricular fibrillation in coronary care units.

PMID- 15155507
TI  - Main presentations of sexually transmitted infections in men.

PMID- 15155508
TI  - Primary angioplasty should be first line treatment for acute myocardial
      infarction: FOR.

PMID- 15155509
TI  - Primary angioplasty should be first line treatment for acute myocardial
      infarction: AGAINST.

PMID- 15155510
TI  - Primary angioplasty or thrombolysis? A topical parable.

PMID- 15155511
TI  - Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: sulfadoxine
      pyrimethamine is not working in Malawi.

PMID- 15155512
TI  - Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: treatment failure
      and resistance in Malawi remain subject for debate.

PMID- 15155513
TI  - Aid may make roads more dangerous than landmines.

PMID- 15155514
TI  - Death on the roads could be the chance of life for some.

PMID- 15155515
TI  - Acquiring accurate crash data is important.

PMID- 15155516
TI  - More on treating homosexuality as a sickness: publication of bigoted letter is
      worrying.

PMID- 15155517
TI  - More on treating homosexuality as a sickness: homosexuality is punishable in
      India.

PMID- 15155518
TI  - Diabetes may be undetected in many children in the UK.

PMID- 15155519
TI  - Implementing guidelines on sudden infant death.

PMID- 15155521
TI  - CSM warning on atypical psychotics and stroke may be detrimental for dementia.

PMID- 15155522
TI  - High-frequency oscillations and seizure generation in neocortical epilepsy.
AB  - Neocortical seizures are often poorly localized, explosive and widespread at
      onset, making them poorly amenable to epilepsy surgery in the absence of
      associated focal brain lesions. We describe, for the first time in an unselected
      group of patients with neocortical epilepsy, the finding that high-frequency (60
      100 Hz) epileptiform oscillations are highly localized in the seizure onset zone,
      both before and temporally removed from seizure onset. These findings were
      observed in all six patients with neocortical epilepsy out of 23 consecutive
      patients implanted with intracranial electrodes for pre-surgical evaluation
      during the study period. The majority of seizures (62%) in these patients were
      anticipated by an increase in high-frequency activity in the 20 min prior to
      neocortical seizure onset. Contrary to observations in normal brain, high
      frequency activity was strongly modulated by behavioural state, and was maximal
      during slow-wave sleep, which may explain the propensity for neocortical onset
      seizures to begin during sleep. These findings point to an important role for
      neuromodulatory circuits, probably involving the thalamus, in mechanisms
      underlying seizure generation in neocortical epilepsy. These findings demonstrate
      that high-frequency epileptiform oscillations may prove clinically useful in
      localizing the seizure onset zone in neocortical epilepsy, for identifying
      periods of increased probability of seizure onset, and in elucidating mechanisms
      underlying neocortical ictogenesis. Confirmation that prolonged bursts of high
      frequency activity may predict focal onset neocortical seizures will require
      prospective validation on continuous, prolonged recordings in a larger number of
      patients. Importantly, the results show that the dynamic range utilized in
      current clinical practice for localization of epileptogenic brain largely ignores
      fundamental oscillations that are signatures of an epileptogenic brain. It may
      prove that many currently available clinical EEG systems and EEG analysis methods
      utilize a dynamic range that discards clinically important information.

PMID- 15155523
TI  - The impact of early and late damage to the human amygdala on 'theory of mind'
      reasoning.
AB  - There is a burgeoning interest in the neural basis of the ability to attribute
      mental states to others; a capacity referred to as 'theory of mind' (ToM). We
      examined the effects of lesions of the amygdala which arise at different stages
      of development on this key aspect of social cognition. Tests of ToM, executive
      and general neuropsychological function were given to subjects with lesions of
      the amygdala arising congenitally or in early childhood ('early damage', n = 15),
      subjects who acquired damage to the amygdala in adulthood ('late damage' n = 11)
      and matched clinical (n = 14) and healthy comparison groups (n = 38). Subjects
      with early damage to the amygdala, particularly if the lesion was associated with
      childhood onset of seizures, were impaired relative to all other groups on more
      advanced tests of ToM reasoning, such as detecting tactless or ironic comments or
      interpreting non-literal utterances. These deficits held for subjects with either
      left or right early amygdala damage and encompassed the understanding of both the
      beliefs and emotional states of others. In contrast, subjects who acquired damage
      to the amygdala in adulthood (usually as part of an anterior temporal lobectomy)
      were not impaired in ToM reasoning relative to both clinical and healthy
      controls, supporting the position that the amygdala is not part of the neural
      circuitry mediating the 'on-line' performance of ToM reasoning. In line with
      theories which claim that ToM is an independent faculty of cognition, we found
      that the pattern of results held after co-varying for measures of executive
      function, memory and general intellectual functioning. We discuss the results in
      the light of recent theories which link early developmental insults to the
      amygdala with the ToM impairments which are thought to be a core neurocognitive
      deficit found in disorders such as autism. We conclude that the amygdala may play
      an important role in the neural systems supporting the normal development of ToM
      reasoning.

PMID- 15155524
TI  - Therapeutic doses of L-dopa reverse hypersensitivity of corticostriatal D2
      dopamine receptors and glutamatergic overactivity in experimental parkinsonism.
AB  - Levodopa (l-dopa) therapy is still considered the gold-standard in the treatment
      of Parkinson's disease. However, the synaptic and cellular mechanisms involved in
      the amelioration of motor symptoms during this treatment are still unclear. To
      address this issue, we analysed the physiological and pharmacological properties
      of striatal glutamatergic and GABAergic synaptic transmission in an experimental
      model of Parkinson's disease. Single-cell recordings were performed in sham
      operated rats, in 6-hydroxydopamine-lesioned animals and in rats receiving
      chronic l-dopa treatment following dopamine (DA) denervation. We utilized a dose
      of l-dopa (10 mg/kg, twice daily for 21 days) able to reverse motor deficits in
      about half of parkinsonian animals. In the striatum of parkinsonian animals
      showing therapeutic benefits following l-dopa treatment, we observed a reversal
      of glutamatergic overactivity and of the hypersensitivity of presynaptic D2 DA
      receptors controlling glutamate release from corticostriatal terminals.
      Conversely, no change was detected in the sensitivity of presynaptic D2 DA
      receptors modulating striatal GABA transmission in both parkinsonian and l-dopa
      treated rats. We suggest that the reversal of striatal glutamatergic overactivity
      and the normalization of hypersensitive D2 DA receptors modulating excitatory
      transmission might underlie some of the therapeutic actions of l-dopa in
      Parkinson's disease.

PMID- 15155525
TI  - Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a
      UK population.
AB  - Twin, family and adoption studies suggest that susceptibility to multiple
      sclerosis is substantially mediated by genetic factors. Linkage to human
      chromosome 17q, homologous to a locus linked to experimental animal models of
      multiple sclerosis, has been widely replicated and the region likely to harbour a
      multiple sclerosis susceptibility gene has recently been refined to a 2.5 Mb
      region of 17q22-24. The candidate multiple sclerosis susceptibility gene, protein
      kinase C alpha (PRKCA), maps within this interval and association with 35 single
      nucleotide polymorphism (SNP) markers, spanning the gene with a median spacing of
      7.8 kb, was tested using a case-control approach. Single-marker genotype and
      estimated haplotype frequencies were compared in UK unrelated cases with multiple
      sclerosis (n = 184) and healthy controls (n = 340) in order to investigate
      association with susceptibility to disease. A haplotype of two SNPs mapping to
      the proximal region of the gene showed evidence for association with
      susceptibility (Bonferroni-corrected P value = 1.1 x 10(-5)). These findings
      suggest that further investigation of the PRKCA gene is warranted, particularly
      in cohorts with evidence of linkage to 17q22. Most of the SNPs investigated in
      this study were intronic and screening to identify disease-associated functional
      mutations is now required. Our results suggest that the promoter and proximal
      gene region should be not only included but prioritized in any screening
      strategy.

PMID- 15155526
TI  - Effect of cardiac myosin binding protein-C on mechanoenergetics in mouse
      myocardium.
AB  - We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on
      contractile efficiency in isovolumically contracting left ventricle (LV) and on
      internal viscosity and oscillatory work production in skinned myocardial strips.
      A 6-week diet of 0.15% 6-n-propyl-2-thiouracil (PTU) was fed to wild-type
      (+/+(PTU)) and homozygous-truncated cMyBP-C (t/t(PTU)) mice starting at age
      approximately 8 weeks and leading to a myosin heavy chain (MHC) isoform profile
      of 10% alpha-MHC and 90% beta-MHC in both groups. Western blot analysis confirmed
      that cMyBP-C was present in the +/+(PTU) and effectively absent in the t/t(PTU).
      Total LV mechanical energy per beat was quantified as pressure-volume area (PVA).
      O2 consumption (Vo2) per beat was plotted against PVA at varying LV volumes. The
      reciprocal of the slope of the linear Vo2-PVA relation represents the contractile
      efficiency of converting O2 to mechanical energy. Contractile efficiency was
      significantly enhanced in t/t(PTU) (26.1+/-2.6%) compared with +/+(PTU) (17.1+/
      1.6%). In skinned myocardial strips, maximum isometric tension was similar in
      t/t(PTU) (18.7+/-2.1 mN x mm(-2)) and +/+(PTU) (21.9+/-4.0 mN x mm(-2)), but
      maximum oscillatory work induced by sinusoidal length perturbations occurred at
      higher frequencies in t/t(PTU) (7.31+/-1.17 Hz) compared with +/+(PTU) (4.48+/
      0.60 Hz) and was significantly more sensitive to phosphate concentration in the
      t/t(PTU). Under rigor conditions, the internal viscous load was significantly
      lower in the t/t(PTU) compared with +/+(PTU), ie, approximately 40% lower at 1
      Hz. These results collectively suggest that contractile efficiency is enhanced in
      the t/t(PTU), probably through a reduced loss of mechanical energy by a viscous
      load normally provided by cMyBP-C and through a gain of phosphate-dependent
      oscillatory work normally inhibited by cMyBP-C.

PMID- 15155527
TI  - Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in
      mice.
AB  - Adipose tissue growth has been proposed to involve recruitment of new blood
      vessels. Here, we test the hypothesis that delivery of an angiogenesis inhibitor
      in mice may prevent diet-induced obesity, the most common type of obesity in
      humans. We show that systemic administration of a selective angiogenesis
      inhibitor, TNP-470 (AGM-1470), prevents obesity in high caloric diet-fed wt mice
      as well as in genetically leptin-deficient ob/ob mice. Inhibition of obesity in
      mice by TNP-470 involves a reduction of vascularity in the adipose tissue. This
      therapeutic strategy appears to selectively affect the growth of adipose tissue
      as measured by the ratio between total fat and lean body mass. Interestingly, the
      treatment with TNP-470 results in decreased serum levels of low-density
      lipoprotein cholesterol. Furthermore, insulin levels are reduced, which indicates
      increased insulin sensitivity, suggesting that angiogenesis inhibitors may
      prevent the development of type II diabetes. Our findings suggest that similarly
      to growth and organogenesis in other tissues, adipose tissue growth is dependent
      on angiogenesis. Our observations may have conceptual implications for the
      prevention of obesity and related disorders.

PMID- 15155528
TI  - Effects of electrical shocks on Cai2+ and Vm in myocyte cultures.
AB  - Changes in intracellular calcium concentration (DeltaCa(i)2+) induced by
      electrical shocks may play an important role in defibrillation, but high
      resolution DeltaCa(i)2+ measurements in a multicellular cardiac tissue and their
      relationship to corresponding Vm changes (DeltaVm) are lacking. Here, we measured
      shock-induced DeltaCa(i)2+ and DeltaV(m) in geometrically defined myocyte
      cultures. Cell strands (width=0.8 mm) were double-stained with Vm-sensitive dye
      RH-237 and a low-affinity Ca(i)2+-sensitive dye Fluo-4FF. Shocks (E approximately
      5 to 40 V/cm) were applied during the action potential plateau. Shocks caused
      transient Ca(i)2+ decrease at sites of both negative and positive DeltaV(m).
      Similar Ca(i)2+ changes were observed in an ionic model of adult rat myocytes.
      Simulations showed that the Ca(i)2+ decrease at sites of DeltaV+m was caused by
      the outward flow of I(CaL) and troponin binding; at sites of DeltaV-m it was
      caused by inactivation of I(CaL) combined with extrusion by Na-Ca exchanger and
      troponin binding. The important role of I(CaL) was supported by experiments in
      which application of nifedipine eliminated Ca(i)2+ decrease at DeltaV+m sites.
      Largest DeltaCa(i)2+ were observed during shocks of approximately 10 V/cm causing
      simple monophasic DeltaV(m). Shocks stronger than approximately 20 V/cm caused
      smaller DeltaCa(i)2+ and postshock elevation of diastolic Ca(i)2+. This was
      paralleled with occurrence of biphasic negative DeltaVm that indicated membrane
      electroporation. Thus, these data indicate that shocks transiently decrease
      Ca(i)2+ at sites of both DeltaV-m and DeltaV+m. Outward flow of I(CaL) plays an
      important role in Ca(i)2+ decrease in the DeltaV+m areas. Very strong shocks
      caused smaller negative DeltaCa(i)2+ and postshock elevation of diastolic
      Ca(i)2+, likely caused by membrane electroporation.

PMID- 15155529
TI  - Msx2 and necdin combined activities are required for smooth muscle
      differentiation in mesoangioblast stem cells.
AB  - Little is known about the molecular mechanism underlying specification and
      differentiation of smooth muscle (SM), and this is, at least in part, because of
      the few cellular systems available to study the acquisition of a SM phenotype in
      vitro. Mesoangioblasts are vessel-derived stem cells that can be induced to
      differentiate into different cell types of the mesoderm, including SM. We
      performed a DNA microarray analysis of a mesoangioblast clone that spontaneously
      expresses an immature SM phenotype and compared it with a sister clone mainly
      composed of undifferentiated progenitor cells. This study allowed us to define a
      gene expression profile for "stem" cells versus smooth muscle cells (SMCs) in the
      absence of differentiation inducers such as transforming growth factor beta. Two
      transcription factors, msx2 and necdin, are expressed at least 100 times more in
      SMCs than in stem cells, are coexpressed in all SMCs and tissues, are induced by
      transforming growth factor beta, and, when coexpressed, induce a number of SM
      markers in mesoangioblast, fibroblast, and endothelial cell lines. Conversely,
      their downregulation through RNA interference results in a decreased expression
      of SM markers. These data support the hypothesis that Msx2 and necdin act as
      master genes regulating SM differentiation in at least a subset of SMCs.

PMID- 15155530
TI  - Vascular endothelial growth factor overexpression in ischemic skeletal muscle
      enhances myoglobin expression in vivo.
AB  - Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is
      considered a promising new therapy for patients with arterial obstructive
      disease. Clinical improvements observed consist of improved muscle function and
      regression of rest pain or angina. However, direct evidence for improved
      vascularization, as evaluated by angiography, is weak. In this study, we report
      an angiogenesis-independent effect of VEGF on ischemic skeletal muscle, ie,
      upregulation of myoglobin after VEGF treatment. Mice received intramuscular
      injection with adenoviral VEGF-A or either adenoviral LacZ or PBS as control,
      followed by surgical induction of acute hindlimb ischemia at day 3. At day 6,
      capillary density was increased in calf muscle of Ad.VEGF-treated versus control
      mice (P<0.01). However, angiographic score of collateral arteries was unchanged
      between Ad.VEGF-treated and control mice. More interestingly, an increase in
      myoglobin was observed in Ad.VEGF-treated mice. Active myoglobin was 1.5-fold
      increased in calf muscle of Ad.VEGF-treated mice (P< or =0.01). In addition, the
      number of myoglobin-stained myofibers was 2.6-fold increased in Ad.VEGF-treated
      mice (P=0.001). Furthermore, in ischemic muscle of 15 limb amputation patients,
      VEGF and myoglobin were coexpressed. Finally, in cultured C2C12 myotubes treated
      with rhVEGF, myoglobin mRNA was 2.8-fold raised as compared with PBS-treated
      cells (P=0.02). This effect could be blocked with the VEGF receptor tyrosine
      kinase inhibitor SU5416. In conclusion, we show that VEGF upregulates myoglobin
      in ischemic muscle both in vitro and in vivo. Increased myoglobin expression in
      VEGF-treated muscle implies an improved muscle oxygenation, which may, at least
      partly, explain observed clinical improvements in VEGF-treated patients, in the
      absence of improved vascularization.

PMID- 15155531
TI  - Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a
      human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell
      cycle arrest.
AB  - Epidemiological studies suggest that the use of NSAIDs and/or a high intake of
      fruit and vegetables reduce the risk of oesophageal adenocarcinoma. Since COX-2
      is up-regulated in Barrett's oesophageal carcinogenesis, the protective effect of
      NSAIDs and natural food components might reflect COX-2 inhibition. We explored
      the effects of quercetin, a natural flavonoid with a potent COX-2 inhibitory
      activity, and two commercially available selective COX-2 inhibitors (NS-398 and
      nimesulide) on cell proliferation, apoptosis, PGE2 production and COX-2 mRNA
      expression in a human oesophageal adenocarcinoma cell line (OE33). Changes in the
      relative numbers of adherent and floating cells were quantified and apoptotic
      cells were identified using ethidium bromide and acridine orange staining under
      fluorescence microscopy. Flow cytometric analysis of adherent and floating cells
      was used to quantify apoptosis and to examine the effects of the agents on the
      cell cycle. After 48 h exposure at concentrations of > or =1 microM both COX-2
      inhibitors and quercetin suppressed cell proliferation (P < 0.01) and increased
      the fraction of floating apoptotic cells. At higher concentrations (50 microM)
      and longer exposure (48 h) the effects of quercetin were significantly greater
      than those of the selective COX-2 inhibitors (P < 0.01). Cell cycle analyses
      showed that quercetin blocked cells in S phase, while the selective COX-2
      inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed
      by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent
      manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2
      production by approximately 70% after 24 h exposure (P < 0.001). We conclude that
      OE33 is a useful model for the study of COX-2 expression and associated phenomena
      in human adenocarcinoma cells. Synthetic COX-2 inhibitors and the food-borne
      flavonoid quercetin suppress proliferation, induce apoptosis and cell cycle block
      in human oesophageal adenocarcinoma cells in vitro, and future studies should
      assess their effects in vivo.

PMID- 15155532
TI  - The PAX5 oncogene is expressed in N-type neuroblastoma cells and increases
      tumorigenicity of a S-type cell line.
AB  - Neuroblastoma is a neural crest-derived neoplasm of infancy with poor outcome in
      patients with advanced disease. The oncogenic transcription factor PAX5 is an
      important developmental regulator and is implicated in the pathogenesis of
      several malignancies. Screening of neuroblastoma cell lines revealed PAX5
      expression in a malignant subset of neuroblastoma cells, so-called 'N-type'
      cells, but not in the more benign 'S-type' neuroblastoma cells. PAX5 expression
      was also detected in small cell lung cancer, an aggressive tumor of neural crest
      origin. Based on this observation we hypothesized that there could be a
      relationship between PAX5 expression and the more malignant phenotype of N-type
      cells. Stable PAX5 expression was established in several clones of the S-type
      cell line CA-2E. A noticeable difference in morphology of these transfectants was
      observed and there was also a significant increase in the proliferation rate.
      Moreover, PAX5 expressing clones gained the ability to form colonies in a soft
      agar assay, a marker of tumorigenicity. Down-regulation of PAX5 in several N-type
      cell lines and one small cell lung cancer cell line utilizing small interfering
      RNA resulted in a significant decrease in growth rate. Taken together we propose
      PAX5 as an important factor for the maintenance of the proliferative and
      tumorigenic phenotype of neuroblastoma. Our data, together with a recent study on
      the role of PAX genes in cancer suggest that PAX5 and other PAX transcription
      factors might be valuable targets for cancer therapy.

PMID- 15155535
TI  - Selective modulation of noradrenaline release by alpha 2-adrenoceptor blockade in
      the rat-tail artery in vitro.
AB  - The effects of blocking alpha(2)-adrenoceptors on noradrenaline (NA) and
      adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves
      have been investigated in rat-tail artery in vitro. Continuous amperometry was
      used to measure NA release and intracellularly recorded excitatory junction
      potentials (e.j.p.'s) were used to measure ATP release. Application of the
      alpha(2)-adrenoceptor antagonist, idazoxan (1 microm), increased the amplitude of
      NA-induced oxidation currents evoked by trains of 10 stimuli at 1 and 10 Hz. In
      cells deep in the media, idazoxan (1 microm) had no effect on the amplitude of
      e.j.p.'s evoked by trains of 10 stimuli at 1 and 10 Hz. In cells close to the
      adventitial - medial border, idazoxan produced a small increase in the amplitude
      of e.j.p.'s evoked at the end of trains of 10 stimuli at 1 Hz. In tissues
      pretreated with the neuronal NA uptake inhibitor, desmethylimpramine (0.3
      microm), idazoxan (1 microm) markedly increased the amplitude of e.j.p.'s in
      cells deep in the media. The alpha(2)-adrenoceptor agonist, clonidine (0.5
      microm), produced similar reductions in the amplitudes of both NA-induced
      oxidation currents and e.j.p.'s evoked by 10 stimuli at 1 Hz. These effects of
      clonidine were reversed by the subsequent addition of idazoxan (1 microm). The
      release of both NA and ATP is inhibited to a similar extent by activation of
      prejunctional alpha(2)-adrenoceptors by clonidine. In contrast, endogenously
      released NA more markedly inhibits NA release. These findings provide further
      support for the differential modulation of NA and ATP release.

PMID- 15155536
TI  - Molecular mechanisms of vasoselectivity of the 1,4-dihydropyridine lercanidipine.
AB  - The effects of (S)- and (R)-lercanidipine on CHO cells stably expressing the
      cardiac (Ca(v)1.2a) or vascular (Ca(v)1.2b) splice variant of the L-type calcium
      channel pore subunit were studied, using whole-cell and single-channel patch
      clamp measurements. Lercanidipine block of Ca(v)1.2b current was
      enantioselective. (S)-lercanidipine was 4.1-fold more potent. Experiments using
      acidic solutions (pH 6.8) revealed a 6.4-fold enhanced inhibitory effect of (S)
      lercanidipine compared with physiological conditions (pH 7.4) indicating that the
      charged form mediates inhibition. At depolarised holding potential (-40 mV), (S)
      lercanidipine exhibited a 35-fold greater potency, compared with standard
      conditions (-80 mV). A comparison of the concentration-dependent inhibition of
      Ca(v)1.2a with Ca(v)1.2b subunit currents by (S)-lercanidipine revealed only a
      1.8-fold difference in IC(50), but the slope of the dose-response curve was much
      steeper (n(H)=2.3) with Ca(v)1.2a, compared with Ca(v)1.2b (n(H)=0.8). This
      indicates overlap between agonistic and antagonistic effects, predominant with
      the cardiac Ca(v)1.2a subunit. This idea is supported by transient stimulatory
      effects, and a slight leftward shift of the IV curves. These effects were more
      prominent for Ca(v)1.2a than for Ca(v)1.2b. Single-channel experiments confirmed
      typical features of calcium channel agonists such as prolonged channel openings,
      a component of lengthened openings, and an enhanced open probability in the
      presence of (S)-lercanidipine. Again, these findings were concentration-dependent
      and more pronounced for Ca(v)1.2a than for Ca(v)1.2b. Our data indicate a splice
      variant predominant agonism as a new mechanism contributing to the
      vasoselectivity of lercanidipine, along with marked voltage-dependence of action.

PMID- 15155534
TI  - Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on
      trigeminal sensory neurons.
AB  - The prototypical aminoalkylindole cannabinoid WIN 55,212-2 (WIN-2) has been shown
      to produce antihyperalgesia through a peripheral mechanism of action. However, it
      is not known whether WIN-2 exerts this action directly via cannabinoid receptors
      located on primary afferents or if other, perhaps indirect or noncannabinoid,
      mechanisms are involved. To address this question, we have examined the specific
      actions of WIN-2 on trigeminal ganglion (TG) neurons in vitro by quantifying its
      ability to modulate the evoked secretion of the proinflammatory neuropeptide CGRP
      as well as the inflammatory mediator-induced generation of cAMP. WIN-2 evoked
      CGRP release from TG neurons in vitro (EC(50)=26 microm) in a concentration- and
      calcium-dependent manner, which was mimicked by the cannabinoid receptor-inactive
      enantiomer WIN 55,212-3 (WIN-3). Moreover, WIN-2-evoked CGRP release was
      attenuated by the nonselective cation channel blocker ruthenium red but not by
      the vanilloid receptor type 1 (TRPV1) antagonist capsazepine, suggesting that,
      unlike certain endogenous and synthetic cannabinoids, WIN-2 is not a TRPV1
      agonist but rather acts at an as yet unidentified cation channel. The inhibitory
      effects of WIN-2 on TG neurons were also examined. WIN-2 neither inhibited
      capsaicin-evoked CGRP release nor did it inhibit forskolin-, isoproteranol- or
      prostaglandin E(2)-stimulated cAMP accumulation. On the other hand, WIN-2
      significantly inhibited (EC(50)=1.7 microm) 50 mm K(+)-evoked CGRP release by
      approximately 70%. WIN-2 inhibition of 50 mm K(+)-evoked CGRP release was not
      reversed by antagonists of cannabinoid type 1 (CB1) receptor, but was mimicked in
      magnitude and potency (EC(50)=2.7 microm) by its cannabinoid-inactive enantiomer
      WIN-3. These findings indicate that WIN-2 exerts both excitatory and inhibitory
      effects on TG neurons, neither of which appear to be mediated by CB1, CB2 or
      TRPV1 receptors, but by a novel calcium-dependent mechanism. The ramifications of
      these results are discussed in relation to our current understanding of
      cannabinoid/vanilloid interactions with primary sensory neurons.

PMID- 15155537
TI  - Pharmacological characterization of canine bradykinin receptors in prostatic
      culture and in isolated prostate.
AB  - The objective of this study was to characterize pharmacologically bradykinin (Arg
      Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, BK) receptors in the canine prostate. Primary
      cultures of canine prostate stromal (PS) and epithelial cells (PE) were
      established and then characterized using cell-specific antibodies (actin,
      vimentin and cytokeratin). Cultured cells were assayed for BK receptors using
      fluorometric imaging plate reader assays. In addition, isolated strips of the
      canine prostate were studied for BK-induced isometric contraction. PS cells were
      labeled only with anti-actin and -vimentin antibodies, while the anti-cytokeratin
      antibodies labeled only the PE cells. In cultured prostate cells, the BK receptor
      2 (B2)-preferring agonist BK induced mobilization of intracellular Ca(2+) in a
      concentration-dependent manner with potencies (log[EC(50)]mid R:PE, pEC(50)) of
      8.72+/-0.12 in PS and 8.75+/-0.06 in PE cells. In contrast, the BK receptor 1
      (B1)-selective agonist [des-Arg(9)]BK (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe) did not
      elicit any significant effect (pEC(50)<5) on Ca(2+) responses. BK agonism (10 nm)
      was inhibited by HOE-140 (D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L
      prolylglycyl-3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahhydro-3
      isoquinolinecarbonyl-L-(2a,3b,7ab)-octahydro-1H-indole-2-carbonyl-L-arginine), a
      B2-selective antagonist, with a log[IC(50)] (pIC(50)) of 8.11+/-0.19 and 9.23+/
      0.20 in PS and PE cells, respectively. [des-Arg(10)]HOE-140 (d-arginyl-l-arginlyl
      l-prolyl-trans-4-hydroxy-l-prolylglycyl-3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4
      tetrahydro-3-isoquinolinecarbonyl-L-(2a, 3b,7ab)-octahydro-1H-indole-2-carbonyl),
      a B1-selective antagonist, displayed weak antagonism with pIC(50) values of
      4.87+/-0.23 and 6.38+/-0.16 in PS and PE cells, respectively. Isolated tissue
      strips of the canine prostate contracted to BK (10 microm) but not to [des
      Arg(9)]BK (10 microm). BK-induced contractility was attenuated by HOE-140 (1
      microm). In conclusion, canine prostates express functional B2 receptors, with no
      apparent B1 receptor subtypes.

PMID- 15155538
TI  - Schaffer collateral and perforant path inputs activate different subtypes of NMDA
      receptors on the same CA1 pyramidal cell.
AB  - The two major inputs to CA1 pyramidal neurons, the perforant pathway (PP) that
      terminates on distal dendrites and the Schaffer collaterals (SCH) that terminate
      on proximal dendrites, activate both AMPA and N-methyl-D-aspartate (NMDA)
      receptors. In an in vitro slice preparation, the pharmacologically isolated NMDA
      receptor-mediated excitatory postsynaptic currents (EPSCs) (NMDA-EPSCs) of either
      pathway can be selectively activated onto a single CA1 pyramidal neuron. Analysis
      of the decay phase of PP and SCH NMDA-EPSCs revealed no significant difference in
      their time constants, suggesting no apparent different distribution in NR2
      subunit composition in the NMDA receptors (NMDAR) activated by the two synaptic
      inputs. However, application of the NR2B-selective antagonist, ifenprodil,
      differently affected the NMDA-EPSCs activated by the PP and SCH inputs. The
      reduction of the PP responses was only 30% compared to 75% for the SCH responses.
      In addition, for both pathways, the ifenprodil-insensitive component of the NMDA
      EPSCs had significantly more rapid decay kinetics than those prior to application
      of ifenprodil. Our results show a greater NR2B subunit contribution to the NMDA
      component of the SCH EPSC, compared to the NMDA component of the PP EPSC and that
      in single CA1 pyramidal neurons NMDA composition is anatomically specific to the
      afferent input.

PMID- 15155539
TI  - Simultaneous central nervous system distribution and pharmacokinetic
      pharmacodynamic modelling of the electroencephalogram effect of norfloxacin
      administered at a convulsant dose in rats.
AB  - The objective of this study was to investigate the contribution of norfloxacin
      blood-brain barrier (BBB) transport to its delayed electroencephalogram (EEG)
      effect in rats. Norfloxacin was injected as a bolus dose of 150 mg kg(-1). Blood
      samples were collected for total norfloxacin plasma concentration measurements.
      The corresponding unbound levels were determined in brain extracellular fluid
      (ECF) using microdialysis. Quantitative EEG recording was conducted during 9 h
      post-dose. Brain ECF norfloxacin concentrations were much lower than plasma
      levels (AUC ratio=9.7+/-2.8%) but peaked very early, and concentration versus
      time profiles were parallel in both biological fluids. The best pharmacokinetic
      (PK) modelling was obtained by considering that ECF concentrations were part of
      the central compartment, with a proportionality factor. The peak of EEG effect
      was delayed and the effect versus plasma concentration curves exhibited a
      dramatic hysteresis. A PK-pharmacodynamic (PD) effect compartment model with a
      spline function to describe the relationship between effect and concentration at
      the effect site successfully described the data. Comparisons of PK-PD parameters
      estimated from plasma and ECF concentrations show that most of the delayed
      norfloxacin EEG effect is not due to BBB transport, but also that PD parameters
      derived from plasma data must be carefully interpreted when drug distribution at
      the effect site is restricted, as may often be the case for centrally acting
      drugs.

PMID- 15155540
TI  - Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and
      displays differential nitric oxide cyclooxygenase-2 expression.
AB  - Injection of carrageenan 1% (50 microl) in the mouse paw causes a biphasic
      response: an early inflammatory response that lasts 6 h and a second late
      response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old,
      weighing 32-34 g, displayed a consistent response in both phases. In 8-week-old
      mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase
      at 6 h and reach their maximum at 24 h to decline to basal value at 48 h.
      Nitrate+nitrite (NO(x)) levels in the paw are maximal after 2 h and slowly
      decline thereafter in contrast to prostaglandin E(2) levels that peak in the
      second phase at the 72 h point. Western blot analysis showed that inducible
      nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX-2) at
      24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS),
      iNOS and COX-2 expression at 6 and 24 h in 3-8-week-old mice demonstrated that
      both eNOS and iNOS expressions are dependent upon the age-weight of mice, as
      opposite to COX-2 that is present only in the second phase of the oedema and is
      not linked to mouse age-weight. Subplantar injection of carrageenan to C57BL/6J
      causes a biphasic oedema that is significantly reduced by about 20% when compared
      to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h,
      as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX
      1) expression is upregulated between 4 and 24 h after carrageenan injection,
      whereas in CD1 mice COX-1 remains unchanged after irritant agent injection. MPO
      levels are maximal at the 24 h point and they are significantly lower, at 6 h
      point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is
      biphasic and age-weight dependent. The present results are the first report on
      the differential expressions of eNOS, iNOS, COX-1 and COX-2 in response to
      carrageenan injection in the two phases of the mouse paw oedema.

PMID- 15155533
TI  - Measuring reactive species and oxidative damage in vivo and in cell culture: how
      should you do it and what do the results mean?
AB  - Free radicals and other reactive species (RS) are thought to play an important
      role in many human diseases. Establishing their precise role requires the ability
      to measure them and the oxidative damage that they cause. This article first
      reviews what is meant by the terms free radical, RS, antioxidant, oxidative
      damage and oxidative stress. It then critically examines methods used to trap RS,
      including spin trapping and aromatic hydroxylation, with a particular emphasis on
      those methods applicable to human studies. Methods used to measure oxidative
      damage to DNA, lipids and proteins and methods used to detect RS in cell culture,
      especially the various fluorescent "probes" of RS, are also critically reviewed.
      The emphasis throughout is on the caution that is needed in applying these
      methods in view of possible errors and artifacts in interpreting the results.

PMID- 15155541
TI  - Acute and long-term effects of nateglinide on insulin secretory pathways.
AB  - Acute and chronic effects of the insulinotropic drug nateglinide upon insulin
      release were examined in the BRIN-BD11 cell line. Nateglinide (10-400 microm)
      stimulated a concentration-dependent increase (P<0.05-P<0.001) in insulin release
      at a non-stimulatory (1.1 mm) glucose concentration. The insulinotropic response
      to 200 microm nateglinide was increased at 30 mm (P<0.01), but not 5.6-16.7 mm
      glucose concentrations. In depolarized cells, nateglinide (50-200 microm) evoked
      K(ATP) channel-independent insulin secretion (P<0.05-P<0.001) in the absence and
      presence of 5.6-30.0 mm glucose (P<0.001). Exposure for 18 h to 100 microm
      nateglinide abolished the acute insulinotropic effects of 200 microm nateglinide,
      tolbutamide or glibenclamide, but had no effect upon the insulinotropic effect of
      200 microm efaroxan. While 18 h exposure to 100 microm nateglinide did not affect
      basal insulin release or insulin release in the presence of 16.7 mm glucose, 25
      microm forskolin or 10 nm PMA, significant inhibition of the insulinotropic
      effects of 20 mm leucine and 20 mm arginine were observed. These data show that
      nateglinide stimulates both K(ATP) channel-dependent and-independent insulin
      secretion. The maintained insulinotropic effects of this drug with increasing
      glucose concentrations support the antihyperglycaemic actions of nateglinide in
      Type II diabetes. Studies of the long-term effects of nateglinide indicate that
      nateglinide shares signalling pathways with sulphonylureas, but not the
      imidazoline efaroxan. This may be significant when considering a nateglinide
      treatment regimen, particularly in patients previously treated with
      sulphonylurea.

PMID- 15155542
TI  - Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina
      pectoris with evidence of severe coronary atherosclerosis in men: The Physicians'
      Health Study.
AB  - BACKGROUND: The relationship of lipoprotein (a) [Lp(a)] concentrations with risk
      of coronary heart disease needs clarification, especially for threshold values
      for increased risk and for possible interactions with LDL-cholesterol
      concentrations and apolipoprotein (a) [apo(a)] size polymorphism. This study was
      designed to examine the ability of baseline Lp(a) concentration and apo(a) size
      to predict future severe angina pectoris in apparently healthy men. METHODS:
      Baseline Lp(a) concentration and apo(a) size were determined in 195 men who
      subsequently developed angina and in 195 men who remained free of cardiovascular
      disease for 5 years. RESULTS: Cases had higher median Lp(a) concentrations than
      did controls (30.6 vs 22.5 nmol/L; P = 0.02). Lp(a) concentration was predictive
      of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0,
      1.8, and 2.6; P for trend = 0.015]. The increased risk was approximately 4-fold
      (95% confidence interval, 1.4- to 11-fold) among men who had Lp(a) above the 95th
      percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile
      and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95%
      confidence interval, 1.5- to 43-fold). Small apo(a) size isoforms also
      significantly predicted risk of angina (RR for lowest quintile = 4.1; P for trend
      = 0.004). When the independent effect of Lp(a) concentration and apo(a) size was
      assessed by including them in the same multivariate model, only the association
      between apo(a) size and risk remained significant. CONCLUSIONS: High Lp(a)
      predicts risk of angina, and the risk is substantially increased with high
      concomitant LDL-cholesterol. Small apo(a) size predicts angina with greater
      strength and independence than Lp(a) concentration.

PMID- 15155544
TI  - Noninvasive glucose monitoring by reverse iontophoresis in vivo: application of
      the internal standard concept.
AB  - BACKGROUND: The GlucoWatch Biographer uses reverse iontophoresis to extract
      glucose across the skin to monitor glycemia in diabetes. The invasive daily
      calibration with a conventional "fingerstick" has been perceived as a
      disadvantage. We used an "internal standard" to render the approach completely
      noninvasive. METHODS: The simultaneous extraction of glucose and sodium by
      reverse iontophoresis was performed on human volunteers over 5 h, and blood
      glucose was measured in the conventional manner at each collection interval.
      These data were used for each volunteer to calculate an extraction constant (K),
      which equals the ratio of the extracted fluxes (JGlucose/JNa+) normalized by the
      corresponding ratio of the concentrations in the blood ([Glucose]/[Na+]). The
      values of K were compared between and within volunteers. RESULTS: The
      iontophoretically extracted glucose flux reflected the glucose concentration
      profiles in the blood, and sodium extraction remained essentially constant,
      consistent with the fact that its systemic concentration does not vary
      significantly. A constant value of K was established for two thirds of the study
      population. However, the efficiency of glucose extraction varied seasonally,
      whereas the reverse iontophoresis of Na+ did not; i.e., variation in K became
      apparent. CONCLUSIONS: Use of the sodium ion as an internal standard could refine
      the determination of glycemia by reverse iontophoresis without requiring
      calibration with a blood sample.

PMID- 15155543
TI  - Evaluation of two nonisotopic immunoassays for determination of glutamic acid
      decarboxylase and tyrosine phosphatase autoantibodies in serum.
AB  - BACKGROUND: Autoantibodies for the 65-kDa form of glutamic acid decarboxylase
      (GAD65) and protein tyrosine phosphatase-like protein (IA-2) are measured for
      risk prediction and diagnosis of autoimmune diabetes mellitus. There is a lack of
      adequate nonisotopic alternatives to the most widely used method for both
      autoantibodies, which is a radiobinding assay (RBA). METHODS: We compared two
      commercially available immunoassays, an ELISA and a time-resolved
      immunofluorometric assay (TR-IFMA), with RBA. RESULTS: We found excellent
      agreement between the RBA and ELISA for measurement of GAD65 autoantibodies
      (GADAs); they showed comparable analytical precision in the cutoff range and
      achieved similar diagnostic specificity. The ELISA identified more GADA-positive
      individuals among patients with new-onset type 1 diabetes than did the RBA [89%
      (95% confidence interval, 78-95%), vs 71% (58-82%); P <0.03]. For IA-2
      autoantibodies (IA-2As), only the TR-IFMA achieved analytical performance and
      diagnostic accuracy comparable to that of the RBA. These results with the GADA
      ELISA and IA-2A TR-IFMA were consistent with those obtained blindly in the
      Diabetes Antibody Standardization Program 2003. The performance of the GADA TR
      IFMA and IA-2A ELISA was unsatisfactory, and these tests were not subjected to
      clinical evaluation. CONCLUSIONS: The GADA ELISA and IA-2A TR-IFMA behave
      comparably with RBA and are thus suitable for use in the clinical laboratory.

PMID- 15155545
TI  - Vitamin D receptor mRNA measured in leukocytes with the TaqMan fluorogenic
      detection system: effect of calcitriol administration.
AB  - BACKGROUND: The aim of the present study was to investigate the interactions
      between the circulating concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      and the mRNA concentration of its specific nuclear receptor in human leukocytes.
      METHODS: We measured vitamin D receptor (VDR) mRNA extracted from leukocytes by
      use of TaqMan fluorescence analysis applied to the reverse transcription-PCR (RT
      PCR) technique in 16 volunteers before and after calcitriol administration. VDR
      mRNA was also measured in leukocytes from calcium-stone-formers (37
      hypercalciuric and 34 normocalciuric patients). The relationship between VDR mRNA
      concentrations and genetic VDR polymorphisms was analyzed in these patients.
      RESULTS: Imprecision (CV) of RT-PCR was 1.3% within assay (n = 10) and 1.7%
      between assays (n = 4). Oral 1,25(OH)2D3 increased mean (SE) serum 1,25(OH)2D3
      1.6 (0.3)-fold and VDR mRNA 1.6 (0.1)-fold 8 h after administration. The maximum
      VDR mRNA was reached 3.6 (1.3) h after 1,25(OH)2D3 ingestion. No differences in
      leukocyte VDR mRNA concentrations were found between normocalciuric and
      hypercalciuric stone-formers in the absence of stimulation. Finally, no
      association was found between VDR mRNA concentrations and genetic VDR
      polymorphisms in stone-formers. CONCLUSIONS: The TaqMan RT-PCR assay is a rapid
      and accurate method to measure VDR mRNA, and leukocytes are a useful model to
      study VDR and 1,25(OH)2D3 interactions. In humans, VDR mRNA is increased by
      agonist 1,25(OH)2D3, a finding resembling previously reported results obtained in
      cellular and animal models.

PMID- 15155546
TI  - Universal RNA reference materials for gene expression.
AB  - A workshop entitled "Metrology and Standards Needs for Gene Expression
      Technologies: Universal RNA Standards" was held in March 2003 to define the
      requirements for standardizing RNA-based molecular assays, specifically
      microarray and quantitative reverse-transcriptase-PCR technologies. NIST
      sponsored the workshop, and participants represented government, industry,
      academia, and clinic. Workshop participants concluded that as a first step, two
      RNA reference materials could be defined that would help in standardization of
      gene-expression technologies: an Assay Process Reference Material, and a
      Universal Array Hybridization Reference Material. The specific characteristics of
      these two standardized materials were broadly outlined. The Assay Process
      Material was proposed to be a pool of 96 expressed human sequences of defined
      composition, cloned in a defined vector and pooled in prescribed ways. The
      Universal Array Hybridization Material was defined as a pool of 12 "alien"
      synthetic sequences not expressed in any known genome to be used to control for
      variability in array hybridization methods. Work is underway at NIST and among
      members of the gene expression array community to further define these materials
      and make them available.

PMID- 15155547
TI  - Potent inhibition by star fruit of human cytochrome P450 3A (CYP3A) activity.
AB  - There has been very limited information on the capacities of tropical fruits to
      inhibit human cytochrome P450 3A (CYP3A) activity. Thus, the inhibitory effects
      of tropical fruits on midazolam 1'-hydroxylase activity of CYP3A in human liver
      microsomes were evaluated. Eight tropical fruits such as common papaw, dragon
      fruit, kiwi fruit, mango, passion fruit, pomegranate, rambutan, and star fruit
      were tested. We also examined the inhibition of CYP3A activity by grapefruit
      (white) and Valencia orange as controls. The juice of star fruit showed the most
      potent inhibition of CYP3A. The addition of a star fruit juice (5.0%, v/v)
      resulted in the almost complete inhibition of midazolam 1'-hydroxylase activity
      (residual activity of 0.1%). In the case of grape-fruit, the residual activity
      was 14.7%. The inhibition depended on the amount of fruit juice added to the
      incubation mixture (0.2-6.0%, v/v). The elongation of the preincubation period of
      a juice from star fruit (1.25 or 2.5%, v/v) with the microsomal fraction did not
      alter the CYP3A inhibition, suggesting that the star fruit did not contain a
      mechanism-based inhibitor. Thus, we discovered filtered extracts of star fruit
      juice to be inhibitors of human CYP3A activity in vitro.

PMID- 15155548
TI  - Validation of (-)-N-3-benzyl-phenobarbital as a selective inhibitor of CYP2C19 in
      human liver microsomes.
AB  - (-)-N-3-Benzyl-phenobarbital (NBPB) was reported to be a potent and selective
      inhibitor of CYP2C19. To validate the selectivity of NBPB toward CYP2C19 in human
      liver microsomes, the inhibitory effects on major cytochrome P450 isoform
      specific reactions were evaluated in the present study. In human liver
      microsomes, NBPB showed potent competitive inhibition on CYP2C19-mediated S
      mephenytoin 4'-hydroxylation with an IC(50) value of 0.25 microM and K(i) value
      of 0.12 microM, whereas weak inhibition was observed for CYP1A2-, CYP2A6-, CYP2B6
      , CYP2C8-, CYP2C9-, CYP2D6-, and CYP3A4-mediated reactions with IC(50) values
      >100, >100, 62, 34, 19, >100, and 89 microM, respectively. Importantly, its
      selectivity toward CYP2C19 among the CYP2C subfamily was demonstrated. Therefore,
      NBPB can be used as a potent and selective inhibitor to establish the relative
      contribution of CYP2C19 for in vitro reaction phenotyping studies. This compound
      can also serve as a positive control inhibitor of CYP2C19 for routine screening
      of P450 reversible inhibition when human liver microsomes are used as the enzyme
      source.

PMID- 15155550
TI  - Molecular cloning of the guinea pig CYP1A2 gene 5'-flanking region:
      identification of functional aromatic hydrocarbon response element and
      characterization of CYP1A2 expression in GPC16 cells.
AB  - Aromatic hydrocarbon (AH) effects are mediated by binding of the AH receptor and
      its heterodimeric partner aromatic hydrocarbon nuclear translocator to specific
      response elements on DNA (AHREs). CYP1A2 expression is induced by AHs, yet AHREs
      have been identified in CYP1A2 genes of only two species and their functional
      role assessed only in the human gene. There have been few analyses of CYP1A2 gene
      regulation in nonhepatic cells. To gain further insight into CYP1A2 regulation,
      we cloned the initial 1.2 kilobases (kb) of the guinea pig CYP1A2 gene 5'
      flanking region and characterized CYP1A2 expression in guinea pig colon
      adenocarcinoma cells (GPC16). Two putative AHRE sites were identified (-830 and 
      575 bp). They are considerably more proximal than the functional AHRE found in
      the human CYP1A2 gene (-2.5 kb). GPC16 cells expressed CYP1A2 after treatment
      with AH, enabling characterization of the putative AHRE sites in a homologous
      cell line. Double-stranded oligonucleotide probes, corresponding to each putative
      AHRE, bound in an AH-induced and specific manner to nuclear proteins prepared
      from GPC16 cells. In transfection analyses, only the distal site mediated AH
      induced reporter gene activity. Mutation of this site suppressed AH-induced
      activity, supporting the concept that it is involved in AH-mediated induction of
      CYP1A2. However, the low level of AH-induction by the wild type suggests that
      other factors modulate AH-response by the CYP1A2 gene.

PMID- 15155551
TI  - A comprehensive quantitative and qualitative evaluation of extrapolation of
      intravenous pharmacokinetic parameters from rat, dog, and monkey to humans. I.
      Clearance.
AB  - This study was conducted to comprehensively survey the available literature on
      intravenous pharmacokinetic parameters in the rat, dog, monkey, and human, and to
      compare common methods for extrapolation of clearance, to identify the most
      appropriate species to use in pharmacokinetic lead optimization, and to ascertain
      whether adequate prospective measures of predictive success are currently
      available. One hundred three nonpeptide xenobiotics were identified with
      intravenous pharmacokinetic data in rat, dog, monkey, and human; both body weight
      and hepatic blood flow-based methods were used for scaling of clearance.
      Allometric scaling approaches, particularly those using data from only two of the
      preclinical species, were less successful at predicting human clearance than
      methods based on clearance as a set fraction of liver blood flow from an
      individual species. Furthermore, commonly used prospective measures of allometric
      scaling success, including correlation coefficient and allometric exponent,
      failed to discriminate between successful and failed allometric predictions. In
      all instances, the monkey tended to provide the most qualitatively and
      quantitatively accurate predictions of human clearance and also afforded the
      least biased predictions compared with other species. Additionally, the
      availability of data from both common nonrodent species (dog and monkey) did not
      ensure enhanced predictive quality compared with having only monkey data. The
      observations in this investigation have major implications for pharmacokinetic
      lead optimization and for prediction of human clearance from in vivo preclinical
      data and support the continued use of nonhuman primates in preclinical
      pharmacokinetics.

PMID- 15155549
TI  - Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic
      glucuronosyltransferases.
AB  - Silybin, a major constituent of the milk thistle, is used to treat several liver
      disorders. Silybin inactivated purified, recombinant cytochromes P450 (P450) 3A4
      and 2C9 in a mechanism-based manner. The inactivations were time-, concentration
      , and NADPH-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl
      )coumarin O-debenzylation activity (P450 3A4) was characterized by a K(I) of 32
      microM, a k(inact) of 0.06 min(-1), and a t(1/2) of 14 min. Testosterone
      metabolism to 6-beta-hydroxytestosterone (P450 3A4) was also inactivated with a
      K(I) of 166 microM, a k(inact) of 0.08 min(-1), and a t(1/2) of 9 min. The 7
      ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified human P450
      2C9 was inactivated with a K(I) of 5 microM, a k(inact) of 0.14 min(-1), and a
      t(1/2) of 7 min. Parallel loss of heme was observed with both P450s. Activity of
      both P450 enzymes was not recovered after removal of silybin either by dialysis
      or by spin gel filtration. In addition, silybin inhibited the glucuronidation of
      7-hydroxy-4-trifluoromethylcoumarin catalyzed by recombinant hepatic UDP
      glucuronosyltransferases (UGTs) 1A1, 1A6, 1A9, 2B7, and 2B15, with IC(50) values
      of 1.4 microM, 28 microM, 20 microM, 92 microM, and 75 microM, respectively.
      Silybin was a potent inhibitor of UGT1A1 and was 14- and 20-fold more selective
      for UGT1A1 than for UGT1A9 and UGT1A6, respectively. Thus, careful administration
      of silybin with drugs primarily cleared by P450s 3A4 or 2C9 is advised, since
      drug-drug interactions cannot be excluded. The clinical significance of in vitro
      UGT1A1 inhibition is unknown.

PMID- 15155552
TI  - A comprehensive quantitative and qualitative evaluation of extrapolation of
      intravenous pharmacokinetic parameters from rat, dog, and monkey to humans. II.
      Volume of distribution and mean residence time.
AB  - Our laboratory is engaged in an ongoing analysis of a 103-compound data set
      containing reliable intravenous pharmacokinetic parameters in the rat, dog,
      monkey, and human, and we have previously reported our findings regarding
      extrapolation of clearance. In this article, we report on our findings regarding
      volume of distribution and mean residence time. Various allometric and
      nonallometric methods were used to predict human volume of distribution based on
      preclinical pharmacokinetic data; clearance and volume of distribution values
      generated by various means were then used to estimate mean residence time. From
      both a quantitative and qualitative perspective, estimating human volume and mean
      residence time based on monkey data alone was the most accurate approach
      evaluated. For volume, estimation based on monkey data alone was quantitatively
      the least biased of all approaches evaluated. Additionally, prediction of mean
      residence time based on clearance and volume from the monkey was the only
      extrapolation method that exhibited a positive, rather than negative, bias. None
      of the allometric scaling approaches investigated afforded optimal predictivity
      for either volume or mean residence time, and neither the correlation coefficient
      nor the allometric exponent allowed a prospective estimation of predictive
      success or failure. These observations regarding volume and mean residence time
      confirm our earlier results with clearance, and further confirm the value of the
      monkey as a species for pharmacokinetic lead optimization.

PMID- 15155553
TI  - Rat and mouse differences in gender-predominant expression of organic anion
      transporter (Oat1-3; Slc22a6-8) mRNA levels.
AB  - Organic anion transporters (Oats) mediate the initial step of active renal
      excretion, specifically substrate uptake into proximal tubule cells. Despite
      extensive characterization of rat Oats, mouse Oat expression patterns are
      virtually unknown. This study was designed to identify basal expression patterns
      of mouse Oat1 (Slc22a6), Oat2 (Slc22a7), and Oat3 (Slc22a8) mRNA, compare these
      patterns with those in rat, and characterize postnatal development of mouse Oat
      mRNA. Tissues were collected from adult male and female 129J and C57BL/6 mice,
      and male and female C57BL/6 mice 0 to 40 days of age. Oat mRNA levels were
      determined by branched DNA signal amplification. Mouse Oat1 mRNA was primarily
      expressed in kidney of both strains, with male predominance. Mouse Oat2 mRNA
      levels were highest in kidney of both strains without gender predominance. In
      both strains, Oat3 mRNA was highest in kidney, and liver expression was male
      predominant. However, only 129J mice had higher Oat3 mRNA levels in female kidney
      than in male kidney. During postnatal development, both Oat1 and Oat2 mRNA levels
      began to rise after 25 days of age. Oat3 mRNA levels rose gradually from birth
      through 40 days of age. Oat2 mRNA increased 30-fold during the first 40 days,
      whereas Oat1 and Oat3 increased about 2-fold. The most notable species
      differences in Oat mRNA expression were a lack of Oat2 female predominance in
      mouse kidney and a less dramatic Oat3 male predominance in mouse liver. With the
      exception of a significant species difference in Oat2 expression, many
      similarities were found between rat and mouse Oat mRNA levels.

PMID- 15155554
TI  - Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver
      microsomes in vitro.
AB  - Some inhibitory agents against CYP2B6 have been reported, but none of these has
      been extensively characterized or compared with others, as to the potency and
      selectivity of inhibition toward CYP2B6. The goal of this work was to find a
      selective and potent chemical in vitro inhibitor toward CYP2B6 using bupropion
      hydroxylation as a model reaction. At the initial screening of more than 30
      substances, ticlopidine, triethylenethiophosphoramide (thioTEPA), metyrapone,
      xanthate C8, and benzylisothiocyanate displayed IC(50) values of <10 microM and
      were selected for a more detailed analysis. Metyrapone, xanthate C8, and
      benzylisothiocyanate inhibited several other cytochrome P450 activities rather
      effectively, some of them even more potently than CYP2B6, and consequently are
      unsuitable as CYP2B6-selective probes. Ticlopidine and thioTEPA were the most
      potent inhibitors of bupropion hydroxylation with K(i) values of 0.2 and 2.8
      microM, respectively. The inhibition type of ticlopidine was found to be mixed
      type, with a component of mechanism-based inhibition, whereas thioTEPA inhibited
      CYP2B6 in a competitive manner. In addition to CYP2B6, ticlopidine also inhibited
      both mephenytoin 4-hydroxylation (CYP2C19) (IC(50), 2.7 microM) and
      dextromethorphan O-demethylation (CYP2D6) (IC(50), 4.4 microM). For thioTEPA the
      next sensitive P450 activity after CYP2B6 was coumarin 7-hydroxylation (IC(50),
      256 microM). Thus, although both compounds proved to be relatively potent
      inhibitors of CYP2B6, thioTEPA was about 2 orders of magnitude more selective
      than ticlopidine. Thus, thioTEPA is a drug of choice when high CYP2B6 selectivity
      among major P450 enzymes is required. Ticlopidine is a useful alternative under a
      controlled experimental setup and when higher potency is needed.

PMID- 15155555
TI  - Physiological modeling of formulated and crystalline 3,3'-diindolylmethane
      pharmacokinetics following oral administration in mice.
AB  - 3,3'-Diindolylmethane (DIM) is a naturally occurring indole, which is currently
      under investigation as a potential chemopreventive agent. The concentrations of
      DIM in plasma, liver, kidney, lung, heart, and brain tissues were determined
      following oral administration of two different formulations to mice (250 mg/kg).
      Mice were sacrificed periodically from 0 to 24 h after administration of either a
      crystalline or an absorption-enhanced formulation (Bio-Response-DIM; Indolplex)
      of DIM, and plasma and tissue concentrations were determined by high-performance
      liquid chromatography (UV detection, 280 nm). A physiologically based
      pharmacokinetic (PBPK) model was developed to characterize the pharmacokinetic
      properties of the two different formulations. The final model included parameters
      reflecting linear first-order absorption, systemic clearance, and distributional
      clearance in the remainder compartment, which were considered independent of
      formulation. All pharmacokinetic profiles from the two formulations were fitted
      simultaneously to estimate unknown model parameters. Plasma and tissue
      concentration-time profiles exhibited a rapid rise to peak values at 0.5 to 1 h,
      followed by a polyexponential decline with an extended terminal phase. These
      profiles were well described by the final model and unknown parameters were
      estimated with relatively low coefficients of variation. Relative drug exposure
      and absorption parameters suggest that BioResponse-DIM exhibited approximately
      50% higher bioavailability than the crystalline formulation. Clearance of DIM was
      estimated as 7.18 ml/h. This is the first study to characterize the
      pharmacokinetics of DIM in mice, and the established PBPK model should prove
      useful in the design and analysis of future preclinical studies aimed at
      evaluating the in vivo pharmacological effects of DIM.

PMID- 15155556
TI  - Metabolic activation of troglitazone: identification of a reactive metabolite and
      mechanisms involved.
AB  - Troglitazone (TGZ), the first glitazone used for the treatment of type II
      diabetes mellitus and removed from the market for liver toxicity, was shown to
      bind covalently to microsomal protein and glutathione (GSH) following activation
      by cytochrome P450 (P450). The covalent binding of (14)C-TGZ in dexamethasone
      induced rat liver microsomes was NADPH-dependent and required the active form of
      P450; it was completely inhibited by ketoconazole (10 microM) and GSH (4 mM). The
      covalent binding in P450 3A4 Supersomes (9.2 nmol of TGZ Eq/nmol P450) was
      greater than that with P450 1A2 (0.7), 2C8 (3.7), 2C19 (1.4), 2E1 (0.6), and 2D6
      (1.1) and 3A5 (3.0). The covalent binding in liver microsomes from rats
      pretreated with dexamethasone (5.3 nmol of TGZ Eq bound/nmol P450) was greater
      than that from rats pretreated with vehicle (3.5), beta-naphthoflavone (0.4),
      phenobarbital (1.1), or pyridine (2.5). A TGZ-GSH adduct was detected by liquid
      chromatography-tandem mass spectrometry and radioactivity detection with a
      deprotonated quasi-molecular ion [M-H](-) at m/z 745, with fragment ions at m/z
      438 (deprotonated TGZ moiety), and at m/z 306 (deprotonated GSH moiety). The TGZ
      GSH adduct was determined to be 5-glutathionyl-5-[4-(6-hydroxy-2,5,7,8
      tetramethylchroman-2-ylmethoxy)benzyl]-thiazolidine-2,4-dione based on collision
      induced dissociation fragmentation, and one- and two-dimensional NMR analysis of
      the isolated adduct. The synthetic 5-hydroxy TGZ and the benzylidene derivative
      of TGZ did not react with GSH or GSH ethyl ester. The mechanisms for metabolic
      activation of TGZ may involve an ultimate reactive sulfonium ion which could be
      formed from an initial sulfoxide followed by a formal Pummerer rearrangement, or
      a C5 thiazolidinedione radical or a sulfur cation radical.

PMID- 15155557
TI  - Validated assays for human cytochrome P450 activities.
AB  - The measurement of the effect of new chemical entities on human cytochrome P450
      marker activities using in vitro experimentation represents an important
      experimental approach in drug development. In vitro drug interaction data can be
      used in guiding the design of clinical drug interaction studies, or, when no
      effect is observed in vitro, the data can be used in place of an in vivo study to
      claim that no interaction will occur in vivo. To make such a claim, it must be
      assured that the in vitro experiments are performed with absolute confidence in
      the methods used and data obtained. To meet this need, 12 semiautomated assays
      for human P450 marker substrate activities have been developed and validated
      using approaches described in the GLP (good laboratory practices) as per the code
      of U.S. Federal Regulations. The assays that were validated are: phenacetin O
      deethylase (CYP1A2), coumarin 7-hydroxylase (CYP2A6), bupropion hydroxylase
      (CYP2B6), amodiaquine N-deethylase (CYP2C8), diclofenac 4'-hydroxylase and
      tolbutamide methylhydroxylase (CYP2C9), (S)-mephenytoin 4'-hydroxylase (CYP2C19),
      dextromethorphan O-demethylase (CYP2D6), chlorzoxazone 6-hydroxylase (CYP2E1),
      felodipine dehydrogenase, testosterone 6 beta-hydroxylase, and midazolam 1'
      hydroxylase (CYP3A4 and CYP3A5). High-pressure liquid chromatography-tandem mass
      spectrometry, using stable isotope-labeled internal standards, has been applied
      as the analytical method. This analytical approach, through its high sensitivity
      and selectivity, has permitted the use of very low incubation concentrations of
      microsomal protein (0.01-0.2 mg/ml). Analytical assay accuracy and precision
      values were excellent. Enzyme kinetic and inhibition parameters obtained using
      these methods demonstrated high precision and were within the range of values
      previously reported in the scientific literature. These methods should prove
      useful in the routine assessments of the potential for new drug candidates to
      elicit pharmacokinetic drug interactions via inhibition of cytochrome P450
      activities.

PMID- 15155558
TI  - Identification of metabolites in urine and feces from rats dosed with the
      heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C).
AB  - 2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic
      and carcinogenic heterocyclic amine formed during ordinary cooking. In model
      systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins
      of animal or vegetable origin. In the present study, the in vivo metabolism of
      MeA alpha C in rats was investigated. Rats were dosed with tritium-labeled MeA
      alpha C, and urine and feces were collected over 3 days. The metabolites of MeA
      alpha C were identified by high performance liquid chromatography-mass
      spectrometry and quantified by liquid scintillation counting. Conjugated
      metabolites were characterized by enzymatic hydrolyzes with beta-glucuronidase or
      arylsulfatase. The data showed that the metabolic pattern of MeA alpha C was
      similar in all rats. About 65% of the dose was excreted in urine and feces, and
      the major amount of MeA alpha C-metabolites was excreted during the first 24 h.
      Thirty-four percent of the dose was found in the rat urine samples collected to
      24 h. In addition to unmetabolized MeA alpha C and two phase I metabolites, 6-OH
      MeA alpha C and 7-OH-MeA alpha C, the following conjugated metabolites were
      identified: MeA alpha C-N(2)-glucuronide, A alpha C-3-CH(2)O-glucuronide, 3
      carboxy-A alpha C and 3-carboxy-A alpha C-glucuronide, and sulfate and
      glucuronide conjugates of 6-OH-MeA alpha C and 7-OH-MeA alpha C. Also, a large
      amount of a rather unstable compound proposed to be of MeA alpha C-N1-glucuronide
      was found. About 21% of the dose was excreted in feces during the first 24 h, and
      MeA alpha C and 7-OH-MeA alpha C were the only compounds identified in feces. Any
      activated metabolites of MeA alpha C were not detected in rat urine or feces.

PMID- 15155560
TI  - Androgen metabolism in thymus of fetal and adult rats.
AB  - Cytochrome P450 (P450) monooxygenases play a role in target tissue metabolic
      activation of xenobiotics and/or endogenous compounds, such as vasoactive
      molecules or hormones. Indeed, tissue-specific metabolism of steroids is
      important in a variety of organs, including thymus, and may alter tissue-specific
      functions. Steroids have been shown to regulate thymus growth and function, but
      surprisingly little is known about expression of the responsible enzyme systems
      in thymus tissue, nor is the thymus-specific biotransformation of testosterone
      known. We therefore investigated gene and protein expression, total protein
      content, and enzyme activity of major P450 isoforms and other key steroid
      metabolizing enzymes in thymus tissue of adult and fetal rats. We detected 6 beta
      hydroxytestosterone (HT), 7 alpha-HT, 16 alpha-HT, 2 alpha-HT, and
      androstenedione to be major testosterone metabolites in the adult thymus. The
      high production of 7 alpha-HT and 16 alpha-HT correlated well with the gene and
      protein expression of CYP2A1/2 and CYP2B1/2 in thymus of adult animals. When
      compared with fetal thymic tissue, CYP2A1/2, 17beta-hydroxysteroid dehydrogenase
      isoform 1 (17 beta-HSDH1) and the androgen receptor were 8-, 3-, and 3-fold more
      highly expressed in adult rats, whereas 17 beta-HSDH2, 17 beta-HSDH3, and 5 alpha
      reductase were reduced to 12%, 0%, and 32% of those in fetal thymus. In
      conclusion, we demonstrated that rat thymus expresses a variety of cytochrome
      P450 monooxygenases and other steroid-metabolizing enzymes, and it successfully
      metabolizes testosterone. Changes of the underlying steroid-metabolizing enzyme
      systems may aid in understanding the role of androgens in altering biological
      functions of the thymus.

PMID- 15155559
TI  - Different in vitro metabolism of paclitaxel and docetaxel in humans, rats, pigs,
      and minipigs.
AB  - We investigated cytochrome P450 (P450)-catalyzed metabolism of the important
      cancer drugs paclitaxel and docetaxel in rat, pig, minipig, and human liver
      microsomes and cDNA-expressed P450 enzymes. In rat microsomes, paclitaxel was
      metabolized mainly to C3'-hydroxypaclitaxel (C3'-OHP) and to a lesser extent to
      C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP), and another unknown
      monohydroxylated paclitaxel. In pig and minipig microsomes, this unknown
      hydroxypaclitaxel was the main metabolite, whereas C3'-OHP was a minor product.
      In minipigs, C2-OHP was the next minor product. In human liver microsomes, 6
      alpha-hydroxypaclitaxel (6 alpha-OHP) was the main metabolite, followed by C3'
      OHP and C2-OHP. Among different cDNA-expressed human P450 enzymes (CYP1A2, 1B1,
      2A6, 2C9, 2E1, and 3A4), only CYP3A4 enzyme formed C3'-OHP and C2-OHP. Docetaxel
      was metabolized in pig, minipig, rat, and human liver microsomes mainly to
      hydroxydocetaxel (OHDTX), whereas CYP3A-induced rat microsomes produced primarily
      diastereomeric hydroxyoxazolidinones. Human liver microsomes from 10 different
      individuals formed OHDTX at different rates correlated with CYP3A4 content.
      Troleandomycin as a selective inhibitor of CYP3A inhibited the formation of C3'
      OHP, C2-OHP, and di-OHP, as well as the unknown OHP produced in rat, minipig, and
      pig microsomes. In human liver microsomes, troleandomycin inhibited C3'-OHP and
      C2-OHP formation, and a suitable inhibitor of human CYP2C8, fisetin, strongly
      inhibited the formation of 6 alpha-OHP, known to be catalyzed by human CYP2C8. In
      conclusion, the metabolism of docetaxel is the same in all four species, but
      metabolism of paclitaxel is different, and 6 alpha-OHP remains a uniquely human
      metabolite. Pigs and minipigs compared with each other formed the same
      metabolites of paclitaxel.

PMID- 15155561
TI  - High level HPV-16 E7 oncoprotein expression correlates with reduced pRb-levels in
      cervical biopsies.
AB  - High-risk human papillomaviruses (HPVs) are major etiological agents of cervical
      cancer. Despite excellent epidemiological evidence for a direct role of HPV-16 in
      cervical carcinogenesis, molecular pathways underlying carcinogenesis in vivo
      remain obscure. The E7 gene is required for immortalization and maintenance of
      the transformed phenotype in vitro; however, little is known about its role for
      tumorigenesis in vivo. The E7 gene codes for an unstable protein the abundance of
      which in cervical biopsies is unknown. We show here that E7 protein levels
      strongly increase during cervical carcinogenesis, underlining its fundamental
      role in cervical cancer. The E7 protein was found predominantly in the nucleus
      and to a minor extent in the cytoplasm in the cervical cancer cell line Ca Ski in
      vitro and in invasive cervical carcinoma in situ, suggesting that nuclear
      resident E7 plays a major role in cervical carcinogenesis in humans. The
      retinoblastoma protein (pRb) is a major E7-target in vitro. We show here that pRb
      expression is initially upregulated in LSIL and disappears in later stages
      concomitant with increased E7 levels, suggesting that E7-driven degradation of
      pRb is involved in cervical tumorigenesis in humans.

PMID- 15155562
TI  - Dynamics and mediators of acute graft attrition after myoblast transplantation to
      the heart.
AB  - Survival and proliferation of skeletal myoblasts within the cardiac environment
      are crucial to the therapeutic efficacy of myoblast transplantation to the heart.
      We have analyzed the early dynamics of myoblasts implanted into the myocardium
      and investigated the mechanisms underlying graft attrition. At 10 min after
      implantation of [14C]thymidine-labeled male myoblasts into female mice hearts,
      14C measurement showed that 39.2 +/- 3.0% of the grafted cells survived, and this
      steadily decreased to 16.0 +/- 1.7% by 24 h and to 7.4 +/- 0.9% by 72 h. PCR of
      male-specific Smcy gene calculated that the total (surviving plus proliferated)
      number of donor-derived cells was 18.3 +/- 1.6 and 23.3 +/- 1.3% at 24 and 72 h,
      respectively, indicating that proliferation of the surviving cells began after 24
      h. Acute inflammation became prominent by 24 h and was reduced by 72 h as
      indicated by myeloperoxidase activity and histological findings. Multiplex RT-PCR
      revealed corresponding changes in IL-1beta, TGF-beta, IL-6, and TNF-alpha
      expression. Treatment with CuZn-superoxide dismutase attenuated the initial rapid
      death and resulted in enhanced cell numbers afterward, giving a twofold increased
      total number at 72 h compared with the nontreatment. This effect was associated
      with reduced inflammatory response, suggesting a causative role for superoxide in
      the initial rapid graft death and subsequent inflammation. These data describe
      the early dynamics of myoblasts implanted into the myocardium and suggest that
      initial oxidative stress and following inflammatory response may be important
      mechanisms contributing to acute graft attrition, both of which could be
      potential therapeutic targets to improve the efficiency of cell transplantation
      to the heart.

PMID- 15155563
TI  - Hydrogen sulfide protects neurons from oxidative stress.
AB  - Hydrogen sulfide (H2S), which is a well-known toxic gas, is found in relatively
      high concentrations in the brain. Although a neuromodulatory role of H2S has been
      demonstrated, little is known of its other biological functions. Here we show
      that H2S protects primary cultures of neurons from death in a well-studied model
      of oxidative stress caused by glutamate, a process called oxidative glutamate
      toxicity--or oxytosis. We found that H2S increases the glutathione levels, which
      normally decrease during the cell death cascade, by enhancing the activity of
      gamma-glutamylcysteine synthetase and up-regulating cystine transport. Cystine
      (cysteine) is the rate-limiting substrate of glutathione synthesis. These
      observations reveal that H2S protects neurons from oxytosis by increasing the
      production of the antioxidant glutathione.

PMID- 15155564
TI  - Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro:
      activation of CREB downstream of GSK3beta.
AB  - In vivo, left ventricular remodeling after myocardial infarction involves
      hypertrophy generally attributed to increased cardiac workload. We hypothesized
      that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied
      several participating kinases and transcription factors in isolated
      cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced
      cardiomyocyte hypertrophy assessed by 3H leucine incorporation and
      immunohistochemistry. Inhibition of reactive oxygen species (ROS),
      serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy.
      In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi
      inhibitor pertussis toxin, blocked reoxygenation-induced hypertrophy. Hypoxia for
      6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding
      activities. However, only CREB DNA-binding was sustained during reoxygenation.
      Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation-induced CREB DNA
      binding without affecting CREB serine-133 phosphorylation. These same pathways
      were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and
      CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation
      blocked the stimulation of CRE-dependent transcription induced by
      hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative
      mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest
      that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB
      activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly
      integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a
      prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to
      cardiac hypertrophy in ischemic heart disease independent of cardiac workload.

PMID- 15155566
TI  - Formation of amyloid aggregates from human lysozyme and its disease-associated
      variants using hydrostatic pressure.
AB  - Formation of amyloid deposits from the Ile56Thr or Asp67His variants of human
      lysozyme is a hallmark of autosomal hereditary systemic amyloidosis. It has
      recently been shown that amyloid fibrils can be formed in vitro from wild-type
      (WT), I56T, or D67H lysozyme variants upon prolonged incubation at acidic pH and
      elevated temperatures (1). Here, we have used hydrostatic pressure as a tool to
      generate amyloidogenic states of WT and variant lysozymes at physiological pH. WT
      or variant lysozyme samples were initially compressed to 3.5 kbar (at 57 degrees
      C, pH 7.4). Decompression led to the formation of amyloid fibrils, protofibrils,
      or globular aggregates, as indicated by light scattering, thioflavin T
      fluorescence, and transmission electron microscopy analysis. Increased 1
      anilinonaphthalene-8-sulfonate binding to the proteins was also observed,
      indicating exposure of hydrophobic surface area. Thus, pressure appears to induce
      a conformational state of lysozyme that aggregates readily upon decompression.
      These results support the notion that amyloid aggregation results from the
      formation of partially unfolded protein conformations and suggest that pressure
      may be a useful tool for the generation of the amyloidogenic conformations of
      lysozyme and other proteins.

PMID- 15155565
TI  - Association of ABCA2 expression with determinants of Alzheimer's disease.
AB  - With the use of a novel method for detecting differential gene expression,
      alterations in functional gene clusters related to transport or oxidative stress
      response and beta-amyloid (Abeta) peptide metabolism were identified in a HEK293
      cell line engineered to overexpress the human ATP binding cassette transporter
      ABCA2. These included fatty acid binding protein, phospholipid binding protein,
      phospholipid synthesis protein, transporter cofactors, seladin-1, Abeta precursor
      protein (APP), vimentin, and low-density lipoprotein receptor-related protein.
      ABCA2 was highly expressed in neuroblastoma cells and colocalized with Abeta and
      APP. Additionally, increased APP protein levels were detected within ABCA2/APP
      double-transfected cells, and increased Abeta was detected in the media of ABCA2
      transfected cells relative to controls. The transporter was abundant in the
      temporal and frontal regions of both normal and Alzheimer's disease (AD) brain
      but was detected at lower concentrations in the parietal, occipital, and
      cerebellar regions. The ABCA2 transfected cell line expressed resistance to a
      free radical initiator, confirming involvement in protection against reactive
      oxygen species and suggesting a further possible link to AD.

PMID- 15155567
TI  - IL-13 and IL-1beta promote lung fibroblast growth through coordinated up
      regulation of PDGF-AA and PDGF-Ralpha.
AB  - Peribronchiolar fibrosis is a prominent feature of airway remodeling in asthma
      and involves fibroblast growth and collagen deposition. Interleukin-13 (IL-13), a
      T-helper 2 cytokine, is a key mediator of airway remodeling in asthma, yet the
      mechanism through which IL-13 promotes fibroblast growth has not been
      investigated. In this study, we show that IL-13 stimulates the mitogenesis of
      mouse, rat, and human lung fibroblasts through release of a soluble mitogen that
      we identified as PDGF-AA. The IL-13-induced growth of human lung fibroblasts was
      attenuated by an anti-PDGF-AA neutralizing antibody, and IL-13 stimulated human
      lung fibroblasts to secrete PDGF-AA. Fibroblasts derived from mouse embryos
      possessing the lethal Patch mutation, which lack the PDGF-Ralpha, showed no
      mitogenic response to IL-13. However, Patch cells did exhibit IL-13-induced STAT
      6 phosphorylation. Stable transfection of the PDGF-Ralpha into Patch cells
      restored the growth response to PDGF-AA and IL-13. Through the use of lung
      fibroblasts from STAT-6-deficient mice, we showed that IL-13-induced PDGF-AA
      release is STAT-6 dependent, but PDGF-AA-induced growth is STAT-6 independent.
      Finally, we showed that IL-1beta enhanced IL-13-induced mitogenesis of rat lung
      fibroblasts through up-regulation of the PDGF-Ralpha. Our findings indicate that
      IL-13 acts in synergy with IL-1beta to stimulate growth by coordinately up
      regulating PDGF-AA and the PDGF-Ralpha, respectively.

PMID- 15155568
TI  - HIV associated neurodegeneration requires p53 in neurons and microglia.
AB  - HIV infection of the central nervous system leads to HIV-associated dementia
      (HAD) in a substantial subset of infected individuals. The pathogenesis of
      neuronal dysfunction in HAD is not well understood, but previous studies have
      demonstrated evidence for activation of apoptotic pathways. The tumor suppressor
      transcription factor p53 is an apical mediator of neuronal apoptosis following a
      variety of injurious stimuli. To determine whether p53 participates in HAD, we
      exposed cerebrocortical cultures from wild-type and p53 deficient mice to the
      neurotoxic HIV envelope protein gp120. Using neuron/microglia co-culture of mixed
      p53 genotype, we observed that both neurons and microglia require p53 for gp120
      induced neuronal apoptosis. Additionally, accumulation of p53 protein in neurons
      was recently reported in post-mortem cortical tissue from a small group of HAD
      patients. Using a much larger cohort of HAD cases, we extend this finding and
      report that p53 protein also increases in non-neuronal cells, including
      microglia. Taken together these findings demonstrate a novel role for p53 in the
      microglial response to gp120. Additionally, these findings, in conjunction with a
      recent report that monocytes expressing HIV-Tat also secrete neurotoxins that
      promote p53 activation, suggest that distinct HIV proteins may converge on the
      p53 pathway to promote neurotoxicity.

PMID- 15155569
TI  - Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in
      trophoblast.
AB  - Hypoxia occurs during the development of placenta in the first trimester and is
      implicated in trophoblast differentiation. Intervillous blood flow increases
      after 10 wk of gestation and results in exposure of trophoblast cells to oxygen.
      Before this time, low oxygen appears to prevent trophoblast differentiation
      toward an invasive phenotype. The oxygen-regulated early events of trophoblast
      differentiation are mediated by TGF-beta3. TGF-beta3 plays a vital role in
      trophoblast differentiation, and its overexpression can be found in preeclamptic
      placenta. We sought to determine the mechanism of TGF-beta3 expression through
      hypoxia-inducible factor (HIF)-1. We show that HIF-1alpha and TGF-beta3 are
      overexpressed in preeclamptic placenta. Hypoxia not only transactivates the TGF
      beta3 promoter activity but also enhances endogenous TGF-beta3 expression. Using
      the TGF-beta3 promoter deletion mutants, we show that the region between -90 and 
      60, which contains a putative HIF-1 consensus motif, is crucial for HIF-1
      mediated transactivation. Electrophoretic mobility shift assays show that HIF-1
      binds to the oligonucleotide containing the HIF-1 motif. Also, introduction of an
      antisense oligonucleotide for HIF-1 diminishes TGF-beta3 expression during
      hypoxia, indicating that the up-regulation of TGF-beta3 by hypoxia is mediated
      through HIF-1. Our results provide evidence that regulation of TGF-beta3 promoter
      activity by HIF-1 represents a mechanism for trophoblast differentiation during
      hypoxia.

PMID- 15155571
TI  - Aquaporin-2 is retrieved to the apical storage compartment via early endosomes
      and phosphatidylinositol 3-kinase-dependent pathway.
AB  - Aquaporin-2 (AQP2) is one of the water-channel proteins expressed in principal
      cells of kidney collecting ducts, where it is stored in the intracellular
      compartment. Previous studies have demonstrated that AQP2 vesicles constitute a
      distinct intracellular compartment partially overlapping with early endosomes. In
      this report, we performed in vitro experiments using the renal epithelial cell
      line, Madin-Darby canine kidney (MDCK) cells, stably expressing AQP2 (MDCK
      hAQP2). In nonpolarized cells, AQP2 vesicles were scattered in the cytoplasm and
      did not colocalize with Golgi 58K or TGN38. Small portions of AQP2 vesicles were
      positive for the lysosome marker cathepsin D. An early endosome antigen (EEA1)
      localized around AQP2 vesicles in close proximity, suggesting involvement of the
      endosomal system in the trafficking of AQP2. AQP2 vesicles are distinct from
      other recycling molecules, such as glucose transporter 4 (GLUT4) and endocytosed
      transferrin. In polarized MDCK-hAQP2 cells, AQP2 vesicles were localized in the
      subapical recycling compartment and distinct from the Golgi apparatus, trans
      Golgi network, lysosome, and early endosome in the nonstimulated state. When the
      cells were treated with forskolin, translocation of AQP2 to the apical membrane
      was observed. Washout of forskolin induced retrieval of AQP2 into the cytoplasm,
      and AQP2 was transiently colocalized with EEA1-positive endosomes. Then, AQP2
      moved from EEA1-positive endosomes to the subapical AQP2-storage compartment,
      which is sensitive to wortmannin and LY294002. These results suggest that AQP2
      resides in a recycling compartment at the apical side in polarized MDCK-hAQP2
      cells, and its retrieval uses the apical endosomal system and the
      phosphatidylinositol 3-kinase-dependent pathway.

PMID- 15155572
TI  - Partial glucocorticoid agonist-like effects of imipramine on hypothalamic
      pituitary-adrenocortical activity, thymus weight, and hippocampal glucocorticoid
      receptors in male C57BL/6 mice.
AB  - Abnormal hypothalamic-pituitary-adrenocortical (HPA) activity may provide clues
      to the neurochemistry of depression. Psychotic depression has one of the highest
      rates of elevated HPA activity and is most often responsive to the tricyclic
      class of antidepressants. Because successful treatment resolves HPA as well as
      psychiatric symptoms, we hypothesized, in light of evidence that tricyclic
      antidepressants can affect glucocorticoid receptor function, that these drugs
      would mimic glucocorticoid feedback inhibition of HPA activity. To test this
      hypothesis, we measured circadian nadir (morning) and peak (evening) as well as
      restraint stress-induced levels of plasma ACTH and corticosterone in
      adrenalectomized (ADX) and sham-ADX (Sham) male C57BL/6 mice after 8 wk of
      imipramine (20 mg/kg/d, ip) or saline treatment. Antidepressant efficacy was
      confirmed by decreased immobility in forced-swim testing. When glucocorticoids
      were low or absent, imipramine mimicked glucocorticoid action in inhibiting
      evening ACTH in ADX mice and tending to inhibit morning corticosterone in Shams.
      However, when glucocorticoid levels were high, imipramine appeared to interfere
      with feedback inhibition by increasing post-stress ACTH and tending to increase
      evening corticosterone in Sham mice. Imipramine also decreased thymus weight in
      ADX and increased thymus weight in Sham mice. Imipramine stimulated morning ACTH
      in ADX mice, possibly by mimicking facilitative effects of high glucocorticoids.
      Short-term imipramine treatment was capable of inducing nuclear translocation of
      hippocampal glucocorticoid receptors in ADX mice. We conclude that imipramine
      effects on glucocorticoid-sensitive endpoints in vivo resemble those of a
      glucocorticoid partial agonist.

PMID- 15155570
TI  - Mechanism of iodide/chloride exchange by pendrin.
AB  - We performed an electrophysiological study to investigate ion transport of
      pendrin and thereby understand the pathogenesis of Pendred syndrome. Using
      pendrin-transfected COS-7 cells, we could show that pendrin transports both
      iodide and chloride measured as voltage-dependent inward and outward membrane
      currents. Chloride in the culture medium, [Cl-]o, was efficiently exchanged with
      cytoplasmic iodide, [I-]i, under physiological concentrations, indicating that
      pendrin is important for chloride uptake and iodide efflux. Although exchange of
      iodide in the medium, [I-]o, with cytoplasmic chloride, [Cl-]i, was observed, a
      significantly high concentration of iodide (10 mm) was required. In addition,
      either iodide or chloride was required on both sides of the cell membrane for the
      anion exchange activity of pendrin, indicating that iodide and chloride activate
      the exchange activity of pendrin while they are transported. The present study
      further supports that pendrin is responsible for the iodide efflux in thyroid
      cells where intracellular iodide concentration is high and that the general
      function of pendrin in other tissues is to transport chloride through exchange
      with other anions.

PMID- 15155573
TI  - Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen
      production and reverses cardiac fibrosis in vivo.
AB  - Cardiac fibrosis is a key component of heart disease and involves the
      proliferation and differentiation of matrix-producing fibroblasts. The effects of
      an antifibrotic peptide hormone, relaxin, in inhibiting this process were
      investigated. We used rat atrial and ventricular fibroblasts, which respond to
      profibrotic stimuli and express the relaxin receptor (LGR7), in addition to two
      in vivo models of cardiac fibrosis. Cardiac fibroblasts, when plated at low
      density or stimulated with TGF-beta or angiotensin II (Ang II), accelerated
      fibroblast differentiation into myofibroblasts, as demonstrated by significantly
      increased alpha-smooth muscle actin expression, collagen synthesis, and collagen
      deposition (by up to 95% with TGF-beta and 40% with Ang II; all P < 0.05).
      Fibroblast proliferation was significantly increased by 10(-8) m and 10(-7) m Ang
      II (63-75%; P < 0.01) or 0.1-1 microg/ml IGF-I (27-40%; P < 0.05). Relaxin alone
      had no marked effect on these parameters, but it significantly inhibited Ang II-
      and IGF-I-mediated fibroblast proliferation (by 15-50%) and Ang II- and TGF-beta
      mediated fibroblast differentiation, as detected by decreased expression of alpha
      smooth muscle actin (by 65-88%) and collagen (by 60-80%). Relaxin also increased
      matrix metalloproteinase-2 expression in the presence of TGF-beta (P < 0.01) and
      Ang II (P < 0.05). Furthermore, relaxin decreased collagen overexpression when
      administered to two models of established fibrotic cardiomyopathy, one due to
      relaxin deficiency (by 40%; P < 0.05) and the other to cardiac-restricted
      overexpression of beta2-adrenergic receptors (by 58%; P < 0.01). These coherent
      findings indicate that relaxin regulates fibroblast proliferation,
      differentiation, and collagen deposition and may have therapeutic potential in
      diseased states characterized by cardiac fibrosis.

PMID- 15155574
TI  - Leptin modulates orexigenic effects of ghrelin and attenuates adiponectin and
      insulin levels and selectively the dark-phase feeding as revealed by central
      leptin gene therapy.
AB  - We tested the hypothesis that leptin acts centrally and peripherally by different
      mechanisms to control peripheral hormones that normally regulate weight
      homeostasis. The paradigm of selectively increasing leptin transgene expression
      with a single intracerebroventricular injection of adeno-associated viral vectors
      encoding leptin (rAAV-lep) or green fluorescent protein (control) in the
      hypothalamus of mutant leptin-deficient ob/ob and wild-type (wt) mice was
      employed in these experiments. rAAV-lep injection increased hypothalamic leptin
      expression in the complete absence of peripheral leptin in ob/ob mice; suppressed
      body weight and adiposity; voluntarily decreased dark-phase food intake;
      suppressed plasma levels of adiponectin, TNFalpha, free fatty acids and insulin,
      concomitant with normoglycemia; and elevated ghrelin levels for extended period.
      Body weight and plasma levels of leptin and metabolic variables were suppressed
      to a lesser extent in rAAV-lep wt mice without decreasing food intake. The
      sustained high leptin transgene expression decreased only the dark-phase phagia
      in both genotypes, but wt mice escaped from leptin restraint during the lights-on
      phase, resulting in normal overall food intake. Leptin administration rapidly
      decreased plasma gastric ghrelin and adipocyte adiponectin but not TNFalpha
      levels, thereby demonstrating a peripheral restraining action of leptin on the
      secretion of hormones of varied origins. Whereas ghrelin administration readily
      stimulated feeding in controls, it was completely ineffective in rAAV-lep-treated
      wt mice. Thus, leptin expressed locally in the hypothalamus counteracted the
      central orexigenic effects of peripheral ghrelin. Cumulatively, these results
      identify newer central and peripheral modulatory influences of leptin on hormonal
      signals of disparate origin implicated in weight homeostasis and metabolic
      disorders.

PMID- 15155575
TI  - Gonadotropin releasing hormone-1 expression in incisors of mice.
AB  - GnRH-1 is a decapeptide hormone that regulates gonadal maturation and fertility.
      In brain, GnRH-1 is secreted by neurons residing mainly in the
      preoptic/hypothalamic area. These neurons arise from cells in the nasal placode
      during embryonic development. GnRH-1 mRNA and peptide in the nonhypothalamic
      region have been described, suggesting other functions of GnRH-1. This paper
      describes for the first time the expression of GnRH-1 in developing incisors in
      mice. At embryonic day (E) 12.5, GnRH-1 mRNA and peptide were localized in cells
      in oral and dental epithelia. At postnatal day (P) 6, before incisor eruption,
      GnRH-1 was expressed in cells in dental epithelial-derived structures that
      include the papillary layer, outer dental epithelium, stellate reticulum, stratum
      intermedium, and enamel-secreting ameloblast cell layer. GnRH-1 expression
      correlated with cell maturity, becoming stronger in cells farther away from the
      proliferative zone. From E12.5 through P6, GnRH-1 expression was not detected in
      neural crest-derived dental mesenchyme or in mesenchyme-derived structures that
      include dental papilla, dental follicle, and dentin-secreting odontoblast. In
      addition, GnRH-1 expression was not detected in molars, indicating that
      expression of GnRH-1 is differentially regulated in incisor vs. molars, with only
      the former exhibiting continuous growth in this species. In homozygous
      hypogonadal mice at P1, GnRH-1 peptide expression was not detected, yet incisors
      were present. However, morphological changes in cells between dental follicle and
      ameloblast cell layer were noted. Taken together, our results indicate that GnRH
      1 expression, although not essential for initiation and formation of incisors,
      may be important in maturation and/or maintenance of these placodally derived
      structures.

PMID- 15155576
TI  - Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing
      hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation
      in cichlid fish.
AB  - GPR54 is a novel G protein-coupled receptor speculated to be essential for sexual
      development. However, its role in the regulation of GnRH types is unknown. To
      address this issue, we cloned GPR54 from the brain of a cichlid fish (tilapia
      Oreochromis niloticus) and determined its expression in immature and mature males
      using our newly developed technique: laser-captured microdissection of single
      digoxigenin-labeled GnRH neurons coupled with real-time quantitative PCR. The
      tilapia GPR54 cDNA contains an open reading frame of 1131 bp encoding 377 amino
      acids and exhibits 56% identity to human GPR54. Absolute copies of GnRH1 and
      GnRH3, not GnRH2, mRNAs were significantly high in mature compared with immature
      males. At the single-cell level, only in mature males, GnRH1 mRNA levels were
      inversely related to GPR54 mRNA (P < 0.002). GPR54 was expressed in a
      significantly high percentage (45.0-60.0%) of mature GnRH1, GnRH2, and GnRH3
      neurons and in immature GnRH3 neurons, which had migrated to the vicinity of
      their final locations in the brain; on the contrary, only 5.0% of immature GnRH1
      and GnRH2 neurons had GPR54 transcripts (P < 0.001). Thus, using a novel
      innovative single-cell gene profiling technique, we provide evidence of the
      structure of a nonmammalian GPR54, which is highly conserved during evolution and
      is expressed in GnRH1, GnRH2, and GnRH3 neurons. Furthermore, we propose that the
      expression of GPR54 is a "stop signal" for GnRH1, GnRH2, and GnRH3 neuronal
      migration, leading to suppression of cell growth and modulation of GnRH
      secretion, which is important for normal sexual development.

PMID- 15155577
TI  - Cocaine- and amphetamine-regulated transcript peptide levels in blood exhibit a
      diurnal rhythm: regulation by glucocorticoids.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptides are novel
      neurotransmitters that are implicated in several physiological functions such as
      control of feeding behavior, drug reward, sensory processing, stress, and
      development. Although a majority of studies have examined the role of CART in the
      brain, less is known about its function in the periphery. Therefore, the goals of
      this study were to examine the levels and species of CART peptides in blood, to
      determine whether they undergo diurnal rhythms, and to elucidate their sources
      and regulatory factors. RIA showed that CART peptides are present in the blood of
      rats and monkeys and that they exhibit a diurnal variation. Western blotting
      confirmed the pattern of diurnal variation in rats and, additionally, showed that
      CART immunoreactivity was due to a single predominant fragment with an apparent
      molecular weight in the range of the active CART 55-102 peptide. Adrenalectomy
      caused a 70% reduction in CART peptide levels in rat blood, and this was reversed
      by corticosterone replacement. CART levels paralleled glucocorticoid levels in
      rat and monkey blood. Control of CART levels by corticosterone suggests the
      possibility that CART peptides in blood may be influenced by hypothalamic
      pituitary-adrenal interactions and that they may play a role in glucocorticoid
      related processes such as stress.

PMID- 15155578
TI  - A mouse with targeted ablation of the growth hormone-releasing hormone gene: a
      new model of isolated growth hormone deficiency.
AB  - The proliferation of pituitary somatotroph cells and the synthesis and secretion
      of GH are under the stimulatory control of the hypothalamic peptide GHRH. GHRH is
      initially synthesized as pre-prohormone and then enzymatically cleaved to its
      mature form (44 amino acids in humans and 42 in mice). Although mutations in the
      GHRH receptor cause isolated GH deficiency (IGHD) both in humans and mice,
      mutations in the GHRH gene have never been described. To determine the
      consequences of generalized lack of GHRH, we have created a mouse with targeted
      disruption (knockout) of the GHRH gene (GHRHKO). We have substituted a portion of
      the gene that encodes for the initial 14 amino acids of the 1-42 GHRH with a
      neomycin resistance cassette. Heterozygous founder (+/-) mice were mated to
      obtain -/- animals. The expected Mendelian ratio was conserved (25.8% of
      offspring were +/+, 52.8% were +/-, and 21.4% were -/-), showing no lethality in
      the GHRHKO embryos. GHRHKO mice appeared normal at birth. Starting at 3 wk of
      age, -/- mice showed significant growth retardation. By 12 wk of age, their
      weight was about 60% of +/+ and +/- littermates. Growth retardation was due to
      IGHD, as shown by reduced pituitary GH mRNA and protein content, reduced serum
      IGF-I, and reduced liver IGF-I mRNA. The phenotype of the GHRHKO mice is similar
      to the one observed in the mouse with mutated GHRH receptor, including pituitary
      hypoplasia. Heterozygous mice had normal growth, although adult +/- males (but
      not females) had mild reduction in serum IGF-I. In conclusion, we demonstrate
      that ablation of the GHRH gene causes IGHD in mice. The GHRHKO mouse will be the
      new useful model of IGHD.

PMID- 15155579
TI  - Chromatin decondensation and nuclear reorganization of the HoxB locus upon
      induction of transcription.
AB  - The colinearity of genes in Hox clusters suggests a role for chromosome structure
      in gene regulation. We reveal programmed changes in chromatin structure and
      nuclear organization upon induction of Hoxb expression by retinoic acid. There is
      an early increase in the histone modifications that are marks of active chromatin
      at both the early expressed gene Hoxb1, and also at Hoxb9 that is not expressed
      until much later. There is also a visible decondensation of the chromatin between
      Hoxb1 and Hoxb9 at this early stage. However, a further change in higher-order
      chromatin structure, looping out of genes from the chromosome territory, occurs
      in synchrony with the execution of the gene expression program. We suggest that
      higher-order chromatin structure regulates the expression of the HoxB cluster at
      several levels. Locus-wide changes in chromatin structure (histone modification
      and chromatin decondensation) may establish a transcriptionally poised state but
      are not sufficient for the temporal program of gene expression. The choreographed
      looping out of decondensed chromatin from chromosome territories may then allow
      for activation of high levels of transcription from the sequence of genes along
      the cluster.

PMID- 15155580
TI  - Snail blocks the cell cycle and confers resistance to cell death.
AB  - The Snail zinc-finger transcription factors trigger epithelial-mesenchymal
      transitions (EMTs), endowing epithelial cells with migratory and invasive
      properties during both embryonic development and tumor progression. During EMT,
      Snail provokes the loss of epithelial markers, as well as changes in cell shape
      and the expression of mesenchymal markers. Here, we show that in addition to
      inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and
      confers resistance to cell death induced by the withdrawal of survival factors
      and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus
      cell division, indicating that with respect to oncogenesis, although a
      deregulation/increase in proliferation is crucial for tumor formation and growth,
      this may not be so for tumor malignization. Finally, the resistance to cell death
      conferred by Snail provides a selective advantage to embryonic cells to migrate
      and colonize distant territories, and to malignant cells to separate from the
      primary tumor, invade, and form metastasis.

PMID- 15155581
TI  - Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association
      with C-terminal BRCT domains of Rad4TOPBP1.
AB  - To gain insight into the function and organization of proteins assembled on the
      DNA in response to genotoxic insult we investigated the phosphorylation of the
      Schizosaccharomyces pombe PCNA-like checkpoint protein Rad9. C-terminal T412/S423
      phosphorylation of Rad9 by Rad3(ATR) occurs in S phase without replication
      stress. Rad3(ATR) and Tel1(ATM) phosphorylate these same residues, plus
      additional ones, in response to DNA damage. In S phase and after damage, only
      Rad9 phosphorylated on T412/S423, but not unphosphorylated Rad9, associates with
      a two-BRCT-domain region of the essential Rad4(TOPBP1) protein. Rad9-Rad4(TOPBP1)
      interaction is required to activate the Chk1 damage checkpoint but not the Cds1
      replication checkpoint. When the Rad9-T412/S423 are phosphorylated, Rad4(TOPBP1)
      coprecipitates with Rad3(ATR), suggesting that phosphorylation coordinates
      formation of an active checkpoint complex.

PMID- 15155584
TI  - Process evaluation of a school-based education program about organ donation and
      registration, and the intention for continuance.
AB  - This paper describes the process evaluation of an organ donation education
      program for high school students aged 15-18 years of which the effectiveness was
      established. The program consisted of three components: a video with group
      discussion, an interactive computer-tailored program and a registration training
      session. A cross-sectional survey was conducted among 50 teachers who had
      recently worked with the program. The results show that all teachers reported to
      have implemented at least two of the three intervention components, while a
      majority of teachers reported to have implemented all components. Teachers'
      attitudes toward the program were generally positive. They reported that the
      opinions of students and colleagues in their own department were most influential
      in their decision to provide the education program. Furthermore, teachers were
      very confident about their ability to apply the different parts of the education
      program. The educational quality of the program was evaluated as moderately
      positive and almost all teachers had the intention to use the program again in
      the future. Because of the positive evaluations and intentions for future
      implementation by teachers, and justified by its previously established
      effectiveness, the education program should be considered for large-scale
      dissemination among high schools in The Netherlands.

PMID- 15155582
TI  - Conservation of the global sex determination gene tra-1 in distantly related
      nematodes.
AB  - Sex determination has long intrigued evolutionists, geneticists, and
      developmental biologists in a similar way. Substantial evidence indicates that
      sex determination evolves rapidly and, therefore, can be used to study how
      molecular patterning processes evolve. In Caenorhabditis elegans, sex
      determination relies on a signaling pathway that involves a cascade of negatively
      acting factors, finally triggering the GLI-family zinc-finger transcription
      factor TRA-1. We have started to investigate sex determination in the nematode
      satellite species Pristionchus pacificus that is separated from C. elegans for
      200-300 million years. In P. pacificus, animals with two X chromosomes develop as
      hermaphrodites, whereas XO animals develop as males. We used an unbiased forward
      genetic approach and isolated several mutants with a hermaphrodite to male
      transformation of the XX karyotype. We identified one complementation group as
      representing the P. pacificus ortholog of tra-1, providing the first evidence for
      the conservation of a global sex determination gene over a time period of at
      least 200 million years. A Ppa-tra-1 morpholino phenocopies Ppa-tra-1 mutants and
      establishes the morpholino technology as a reverse genetic approach in P.
      pacificus.

PMID- 15155583
TI  - The T-box transcription factor Tbx18 maintains the separation of anterior and
      posterior somite compartments.
AB  - The compartmentalization of somites along their anterior-posterior (AP) axis is
      pivotal to the segmental organization of the vertebrate axial skeleton and the
      peripheral nervous system. Anterior and posterior somite halves contribute to
      different vertebral elements. They are also characterized by different
      proliferation rates and properties with respect to neural crest cell migration
      and spinal nerve passage. AP-somite polarity is generated in the anterior
      presomitic mesoderm by Mesp2 and Delta/Notch signaling. Here, we demonstrate that
      maintenance of AP-somite polarity is mediated by the T-box transcription factor
      Tbx18. Mice deficient for Tbx18 show expansion of pedicles with transverse
      processes and proximal ribs, elements derived from the posterior lateral
      sclerotome. AP-somite polarity is established in Tbx18 mutant embryos but is not
      maintained. During somite maturation, posterior somite compartments expand most
      likely because of posterior cells invading the anterior somite half. In the
      anterior lateral sclerotome, Tbx18 acts as an antiapoptotic factor. Ectopic
      expression experiments suggest that Tbx18 can promote anterior at the expense of
      posterior somite compartments. In summary, Tbx18 appears to act downstream of
      Mesp2 and Delta/Notch signaling to maintain the separation of anterior and
      posterior somite compartments.

PMID- 15155585
TI  - A cost-effective approach to the development of printed materials: a randomized
      controlled trial of three strategies.
AB  - Printed materials have been a primary mode of communication in public health
      education. Three major approaches to the development of these materials--the
      application of characteristics identified in the literature, behavioral
      strategies and marketing strategies--have major implications for both the
      effectiveness and cost of materials. However, little attention has been directed
      towards the cost-effectiveness of such approaches. In the present study, three
      pamphlets were developed using successive addition of each approach: first
      literature characteristics only ('C' pamphlet), then behavioral strategies ('C +
      B' pamphlet) and then marketing strategies ('C + B + M' pamphlet). Each pamphlet
      encouraged women to join a Pap Test Reminder Service (PTRS). Each pamphlet was
      mailed to a randomly selected sample of 2700 women aged 50-69 years.
      Registrations with the PTRS were monitored and 420 women in each pamphlet group
      were surveyed by telephone. It was reported that the 'C + B' and 'C + B + M'
      pamphlets were significantly more effective than the 'C' pamphlet. The 'C + B'
      pamphlet was the most cost-effective of the three pamphlets. There were no
      significant differences between any of the pamphlet groups on acceptability,
      knowledge or attitudes. It was suggested that the inclusion of behavioral
      strategies is likely to be a cost-effective approach to the development of
      printed health education materials.

PMID- 15155586
TI  - Representing young people's sexuality in the 'youth' media.
AB  - This paper reports findings from a content analysis of the main messages about
      sexuality in media outlets consumed by young people. It examines how sexuality is
      represented and the level of sexual health information provided in some UK
      magazines and TV programmes targeted at young people. Our findings show that such
      outlets included a vast range of useful discussion including information about
      health concerns and in-depth exploration of issues such as consent and examples
      of couples exploring whether or not they were 'ready' for sex. In particular, the
      right of girls to 'say no' was vividly fore-grounded in several teen dramas and
      magazines. However, coverage was also characterized by certain limitations. A
      clear pattern was evident whereby contraception and managing 'how far to go' were
      depicted as women's responsibility. There was a limited range of representations
      for young men, a lack of positive images of lesbian and gay teenagers, and a
      failure to represent diversity. There were also no examples of how people might
      raise concerns such as safer sex. In this context, health educators need to be
      aware of both the richness and the limitations of current mainstream
      representations in order to work with and through the media to improve the
      quality and range of material for young people.

PMID- 15155587
TI  - Smoking initiation among Gambian adolescents: social cognitive influences and the
      effect of cigarette sampling.
AB  - In this study, determinants of tobacco use among Gambian youths were examined. A
      cross-sectional school-based survey was conducted among 282 students, aged 14-18.
      The potential determinants were derived from the core constructs of the Theory of
      Planned Behavior and the ASE model. Moreover, various measures of knowledge and
      media influence were added to the research model. The results show that free
      cigarette offers by representatives of tobacco companies were mostly responsible
      for the difference between smokers and non-smokers. Other variables associated
      with smoking behavior were greater intention to smoke in the future, lower self
      efficacy expectations regarding emotional situations, smoking behavior of the
      respondent's best friend, the mother having a job and the absence of other family
      members living in the house. Our study supports current efforts to prohibit
      tobacco advertising and promotions in The Gambia, especially the distribution of
      free samples. Additionally, we recommend prevention activities in schools and
      communities to aim at making children less vulnerable to 'sampling', increasing
      their self-efficacy expectations regarding emotional situations and making them
      aware of the influence of their best friend.

PMID- 15155588
TI  - Developing complex interventions for rigorous evaluation--a case study from rural
      Zimbabwe.
AB  - Much attention has been placed on the need to develop and evaluate complex
      interventions targeting public health issues, such as reproductive health.
      However, and as has been the case in the recent past, even well-designed trials
      will be flawed unless meticulous attention is paid to ensuring the most
      appropriate intervention is designed and developed. This requires a well
      resourced and carefully planned feasibility study, incorporating both formative
      and process evaluation, with particular attention being paid to the context of
      the proposed intervention. In this paper, we describe the way in which a
      feasibility study helped redesign and shape a complex intervention targeting
      adolescent sexual health in rural Zimbabwe. By using a mixture of in-depth
      interviews, focus groups and participant observation with pupils, parents,
      teachers and education officers, we were able to show that the intervention as
      originally conceived was unlikely to be deliverable. Process evaluation findings
      from the feasibility study led to substantial changes to both the content and
      delivery of the proposed intervention, which is now subject to testing for
      effectiveness in a large community randomized trial.

PMID- 15155589
TI  - Network 'norms' or 'styles' of 'drunken comportment'?
AB  - Much of what is qualitatively known about alcohol consumption derives from
      anthropological studies, focusing on the macro or structural level, involving
      cultural 'norms' within either 'wet' or 'dry' societies. However, we argue for a
      meso, social network rather than 'societal' level of analysis and a focus not on
      societal 'norms', but on 'styles' of 'drunken comportment' within these networks.
      Although most 'drunken comportment' is acknowledged as excusable by the fact that
      alcohol has been consumed, some networks place a tighter 'within-limits' boundary
      on their own behavior than others. We illustrate this through the talk of two
      girl groups within the same social network in a secondary school, who both
      consume alcohol as a means of performing sociability. Both groups claim
      'disinhibition' as a primary goal of alcohol consumption, but important
      differences are observed in placing 'limits' on 'disinhibition', especially with
      regards to subsequent sexual behavior. This highlights inadequacies for health
      promotion programmes.

PMID- 15155590
TI  - An application of the Theory of Planned Behaviour to blood donation: the
      importance of self-efficacy.
AB  - Given that self-efficacy has emerged as a key construct in health psychology,
      this study set out to explore its utility in the context of blood donation as
      defined within the Theory of Planned Behaviour (TPB). An Ajzen and Fishbein-type
      questionnaire was administered to 100 undergraduate students at the University of
      Ulster, Coleraine. A hierarchical multiple regression analysis provided strong
      support for the role of self-efficacy as a major determinant of intention. It not
      only helped to explain some 73% of the variance, but also made a greater
      contribution to the prediction of intention than the other main independent
      variables of the model-past behaviour and self-identity. Demonstrating the
      utility of self-efficacy in the context of blood donor behaviour not only has
      several important practical implications, but serves to further highlight its
      importance within the TPB.

PMID- 15155591
TI  - The impact and evaluation of two school-based interventions on intention to
      register an organ donation preference.
AB  - The present paper describes the impact and evaluation of two intervention
      components-a video with group discussion and an interactive computer-tailored
      program-in order to encourage adolescents to register their organ donation
      preference. Studies were conducted in school during regular school hours. The
      video with group discussion in class had a positive impact on the intention to
      register an organ donation preference as well as on the intention to register as
      a posthumous organ donor. The computer-tailored program had no surplus value when
      compared to reading an extensive brochure with general information on organ
      donation. However, participants appreciated the tailored information more than
      the brochure. It may be that having provided general information before exposure
      to the tailored program, the tailored intervention will be more effective. This
      needs to be tested in a further experiment.

PMID- 15155593
TI  - The Stages of Change in three stage concepts and two modes of physical activity:
      a comparison of stage distributions and practical implications.
AB  - Stages of Change were assessed for three stage definitions and two modes of
      health-enhancing physical activity (HEPA) in a representative telephone survey in
      Switzerland (participation 55.8%; n = 1471). Two five-stage definitions focusing
      either on intention to change or current behavior were integrated into a seven
      stage concept, taking into account both aspects. The two target behaviors were
      activities with at least moderate intensity and activities with vigorous
      intensity. According to the two five-stage definitions, at least half of the
      participants were either in precontemplation (focus on intention) or in
      preparation (focus on behavior). Upon classification into the seven stages these
      large stage groups were differentiated. There were differences in the pros for
      change between the new stages of the seven-stage concept. One in seven
      participants was regularly active according to the moderate criteria, but not
      using the vigorous criteria, and one in every eight participants reported the
      inverse. Results show that an individual can be in different Stages of Change
      depending on the stage definition and be regularly active or not depending on the
      target behavior. The practical implications of the seven-stage algorithm and a
      two-dimensional matrix to classify participants for both moderate and vigorous
      intensity activities in an Internet-based HEPA program are presented.

PMID- 15155594
TI  - Unraveling women's perceptions of risk for breast cancer.
AB  - Inconsistent reports of the prevalence of risk perception accuracy may be related
      to the use of different classification strategies. The purpose of this study was
      to compare two approaches for assessing the accuracy of women's breast cancer
      risk perceptions. A telephone survey was conducted with an age-stratified random
      sample of British Columbian women 20-79 years of age without a breast cancer
      diagnosis (n = 761). A comparison of two methods employed to determine perception
      accuracy revealed substantial differences between the methods with regard to the
      classification of women as under- and over-estimators. The study highlights the
      need for researchers to consider the method used to determine the accuracy of
      risk perceptions and the implications of using different strategies to assess
      risk perception accuracy when such information is used in research or to guide
      interventions.

PMID- 15155595
TI  - Periconceptional smoking: an exploratory study of determinants of change in
      smoking behavior among women in the fertile age range.
AB  - How can women who are not yet pregnant be motivated to stop smoking before they
      become pregnant? Epidemiological studies have suggested that periconceptional
      smoking and smoking during the first trimester of the pregnancy may lead to
      congenital abnormalities. To motivate women to stop smoking before pregnancy,
      more insight is needed into the differences between 'smoking' women who want to
      have children and those who do not. A sample of 931 women (65% response rate)
      aged 15-45 years returned a questionnaire with questions about their smoking
      behavior, wish to have children, risk perceptions, attitude to smoking, personal
      efficacy and stage of readiness to change. In spite of some positive outcomes
      (e.g. negative attitude to smoking, relatively high risk perceptions of the
      relationship between congenital anomalies and smoking), one cannot automatically
      assume that these women will stop smoking before they get pregnant. (1) Beliefs,
      attitude and readiness to change were not well integrated and grounded
      cognitively. (2) Women who smoked were pessimistic about their ability to quit.
      Future campaigns need to 'invite' women to associate and to integrate risk
      information about the relationship between smoking and congenital abnormalities
      with other cognitions (attitude, intention). It is also important to instruct
      women in how to stop smoking and to remain non-smokers.

PMID- 15155596
TI  - Follow-up study of a school-based scalds prevention programme.
AB  - This paper describes the follow-up evaluation of a school-based scalds prevention
      programme designed to teach children about scalds hazards and encourage safe
      family practices. It involved two classroom sessions and a homework exercise that
      targeted five safety practices. The programme was taught to 28 classes in 14
      schools in Waitakere City, New Zealand by Public Health Nurses (PHNs). Children
      (n = 116) aged 10-11 years from three of the schools in ethnically diverse,
      low/middle-income areas were assessed for their knowledge of scalds hazards 1
      year after the programme. They recalled a mean of 7.46 out of 10 hazards, which
      was almost equivalent to children in an earlier evaluation who recalled 7.62
      hazards immediately after the teaching. Altogether, 65-79% of children reported
      that each of the four safety items provided were at least temporarily used as
      intended, with 29-55% reporting that they were still in use 1 year later.
      Interviews with children's parents (n = 18) indicated that the majority of their
      hot water practices were not optimally safe prior to the programme and that many
      had adopted the suggested practices. While the PHNs were positive about the
      programme, they suggested teachers could deliver it as part of the school
      curriculum.

PMID- 15155597
TI  - Learning to DISCERN online: applying an appraisal tool to health websites in a
      workshop setting.
AB  - This study examined the application of DISCERN-validated criteria for judging the
      quality of printed information on treatment-to online health information in a
      workshop setting. A survey was conducted amongst 57 participants attending
      DISCERN Online workshops. Participants were health information users-health care
      and information providers, consumers (patients/carers), and consumer
      representatives. Workshops involved using DISCERN to appraise a health website.
      Participants completed questionnaires before and after the workshop, and at 2
      months follow-up. Responses revealed that participants accessed online health
      information for professional (85.7%) and personal (75%) reasons. Less than half
      (41%) had applied some form of quality criteria to online information prior to
      attending the workshop. Despite varying levels of expertise, participants found
      DISCERN and the supporting materials accessible. The majority (96.2%) agreed
      DISCERN would help users discriminate between high- and low-quality online
      treatment information, and would be applicable to a wide variety of such
      information. At follow-up, most (89.6%) reported that their attitude to consumer
      health information of all types had changed-mostly becoming more critical or
      systematic. It is possible that general schemes such as DISCERN will provide
      users with simple and flexible skills for dealing with the wide range of
      treatment information available.

PMID- 15155598
TI  - Media interventions to increase cervical screening uptake in South Africa: an
      evaluation study of effectiveness.
AB  - Successful cervical cancer prevention depends on reaching, screening and treating
      women with pre-invasive disease. We aimed to evaluate the effectiveness of two
      media interventions-a photo-comic and a radio-drama-in increasing cervical
      screening uptake. A randomized controlled trial compared a photo-comic on
      cervical cancer screening with a placebo comic. One month after the comics were
      distributed a radio-drama paralleling the photo-comic was broadcast on the
      community radio station and a retrospective evaluation was carried out. The trial
      was set in Khayelitsha, a peri-urban squatter community near Cape Town, South
      Africa. A random sample consisted of 658 women between the ages of 35 and 65
      years, from a stratified sample of census areas. The main outcome measure was
      self-reported cervical screening uptake 6 months after distribution of the
      comics. Seven percent (18 of 269) of women who received the intervention photo
      comic reported cervical screening during the 6 months follow-up, compared with 6%
      (25 of 389) of controls (P = 0.89). Women who recalled hearing the radio-drama
      were more likely to report attending screening (nine of 53, 17%) than those who
      did not (19 of 429, 4%; P < 0.001). We conclude that the photo-comic was
      ineffective in increasing cervical screening uptake in this population. The radio
      drama may have had more impact, but only a minority of women recalled being
      exposed to it. Future research must concentrate not only on achieving high level
      of exposure to health messages, but also on investigating the links between
      exposure and action.

PMID- 15155599
TI  - Creating parsimony at the expense of precision? Conceptual and applied issues of
      aggregating belief-based constructs in physical activity research.
AB  - The aggregation of measured social cognitive beliefs to form scales is a common
      procedure in physical activity research. In this paper, we propose that specific
      beliefs may actually have unique associations with physical activity, which are
      obscured by the practice of aggregation. Further, we point out that beliefs may
      be related in a more complex manner than the theory behind scale aggregation.
      Both of these factors are interpreted in terms of limiting physical activity
      intervention efforts. Therefore, the purpose of this study was to examine
      alternatives to summative scales of physical activity beliefs using structural
      equation modeling. Demonstrations were performed using belief-based constructs of
      self-efficacy, pros and cons with a large Canadian random sample (N = 683) over
      three, 6-month time points. Results demonstrated that items of belief-based
      scales are multidimensional and that a correlated belief structure fit the
      observed data better (P < 0.05) and explained more variance in vigorous physical
      activity (an additional 6-7%) than aggregated scales. Finally, a causally ordered
      structure among beliefs was supported, suggesting that items within a scale may
      be linked causally rather than as indicators of a higher-order latent variable.
      Implications for future research and physical activity interventions are
      discussed.

PMID- 15155602
TI  - Use of artificial dermis and recombinant basic fibroblast growth factor for
      creating a neovagina in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Vaginal agenesis is an uncommon, but not rare, condition. Although there are many
      methods for creating a neovagina, the optimal treatment is unknown. An 18-year
      old woman with Mayer-Rokitansky-Kuster-Hauser syndrome received vaginoplasty with
      a modified Wharton procedure using an artificial dermis (atelocollagen sponge).
      From 10 days after the operation, the patient was administered human recombinant
      basic fibroblast growth factor (bFGF) spray to accelerate epithelialization on
      the neovagina. At 50 days after the operation, we confirmed histological squamous
      epithelialization of the vaginal epithelium. At 12 months after the operation,
      the neovagina was at least 3.5 cm in width and approximately 8 cm in length. In
      this case, use of artificial dermis and recombinant bFGF to create a neovagina
      was an easy, less invasive and useful method.

PMID- 15155603
TI  - Elevated progesterone at initiation of stimulation is associated with a lower
      ongoing pregnancy rate after IVF using GnRH antagonists.
AB  - BACKGROUND: The objective of this prospective study was to assess the impact of
      elevated serum progesterone levels on day 2 of the cycle on pregnancy rates in
      patients treated by IVF using GnRH antagonists. METHODS: Ovarian stimulation was
      started on day 2 of the cycle if progesterone levels were normal (normal-P group,
      n = 390). In the presence of elevated progesterone, initiation of stimulation was
      postponed for 1 or 2 days (high-P group, n = 20) and was started if repeat
      progesterone levels returned to normal range (n = 16). Stimulation was performed
      with recombinant FSH (rFSH) and GnRH antagonist was always started on day 6 of
      stimulation. RESULTS: A significantly higher exposure to progesterone and a
      significantly lower exposure to estradiol was present in the high-P as compared
      with the normal-P group from day 1 to day 8 of stimulation. In addition, a
      significantly lower ongoing pregnancy rate both per started cycle (5.0% versus
      31.8%; P = 0.01) and per embryo transfer (6.3% versus 36.9%; P = 0.01) was
      present in the high-P compared with the normal-P group, respectively.
      CONCLUSIONS: The presence of elevated serum progesterone on day 2 of the cycle is
      associated with a decreased chance of pregnancy in patients treated with rFSH and
      GnRH antagonists.

PMID- 15155604
TI  - Disparate effects of relaxin and TGFbeta1: relaxin increases, but TGFbeta1
      inhibits, the relaxin receptor and the production of IGFBP-1 in human endometrial
      stromal/decidual cells.
AB  - BACKGROUND: The purpose of this study was to determine the effect of progestin,
      relaxin (RLX) and transforming growth factor beta1 (TGFbeta1) on the content of
      relaxin receptor (LGR7) mRNA. The effect of RLX on insulin-like growth factor
      binding protein-1 (IGFBP-1) production was determined to evaluate the biological
      function of RLX/receptor in human endometrial cells. METHODS AND RESULTS: The
      levels of LGR7 mRNA and the effect of hormones were determined by real-time PCR
      in endometrial cells. LGR7 mRNA was found to be relatively abundant in
      endometrial glands and decidual cells and much less in endometrial stromal cells.
      In stromal cells, medroxyprogesterone acetate (MPA), or MPA plus RLX,
      significantly increased the LGR7 mRNA and RLX alone had little effect. In
      decidual cells, RLX increased LGR7 mRNA in a dose- and time-dependent fashion.
      TGFbeta1 reduced the LGR7 mRNA. In stromal cells, MPA alone caused a slight
      increase (2-4-fold) of the production rate of IGFBP-1 whereas MPA plus RLX
      synergistically increased (>40-fold) the IGFBP-1 production. In decidual cells in
      which the basal production rate was already approximately 50-fold higher than in
      stromal cells, RLX alone caused an additional increase (>30-fold) on the
      production rate. TGFbeta1 inhibited the IGFBP-1 production. CONCLUSION: The
      present study showed that in undifferentiated endometrial stromal cells,
      progestin increases the RLX receptor content to enhance the effect of RLX on the
      target gene (IGFBP-1). In decidual cells, RLX alone up-regulates its receptor,
      resulting in a large scale induction of IGFBP-1. TGFbeta1 has an inhibitory
      effect on LGR7 and IGFBP-1.

PMID- 15155605
TI  - Sex differences in FSH-regulatory peptides in pubertal age boys and girls and
      effects of sex steroid treatment.
AB  - BACKGROUND: FSH concentrations are higher in girls than in boys before puberty.
      We hypothesized that steroid-mediated changes in FSH-regulatory proteins underlie
      the sex differences in FSH secretion and pubertal timing. METHODS: FSH-regulatory
      proteins, LH, FSH and sex steroids were measured in five boys, 10 girls, and five
      girls with Turner syndrome before and during sex steroid treatment (girls, 0.05
      mg/day estradiol; boys, 5 mg/day testosterone) for up to 4 weeks. Blood was
      obtained every 15 min from 20.00 to 08.00 h before and during sex steroid
      treatment. RESULTS: The mean FSH concentration was higher in girls than in boys
      (P = 0.0044). Activin-A concentrations were greater (P < 0.0001) and inhibin-B
      concentrations lower (P < 0.0001) in girls compared with boys. Steroid treatment
      (i) suppressed LH/FSH concentrations in all subjects; (ii) increased the mean
      activin-A concentration in all but the Turner girls (P = 0.001); and (iii)
      decreased inhibin-B concentrations in boys (P = 0.005) but not in girls. Total
      follistatin and follistatin 288 concentrations did not differ by sex.
      CONCLUSIONS: Sex steroids regulate circulating activin-A and inhibin-B
      concentrations in children. The lower inhibin-B and higher activin-A
      concentrations may explain the higher FSH and earlier onset of puberty in girls.

PMID- 15155606
TI  - Coasting acts through downregulation of VEGF gene expression and protein
      secretion.
AB  - BACKGROUND: This study was conducted to investigate the mechanisms by which
      coasting may be effective in decreasing the incidence of ovarian hyperstimulation
      syndrome (OHSS). METHODS: A total of 160 women (patients and oocyte donors)
      undergoing coasting and 116 controls were included in the study. Serum,
      follicular fluid and granulosa cells were collected on the day of oocyte
      retrieval. Vascular endothelial growth factor (VEGF) concentrations were
      determined using an enzyme-linked immunosorbent assay (ELISA). Real-time PCR was
      performed to evaluate VEGF gene expression in granulosa cells. Cell death was
      studied by flow cytometry using annexin V-fluorescein isothiocyanate (FITC) and
      counterstaining by propidium iodide, and double staining with CD45 monoclonal
      antibody was performed to distinguish the contamination of apoptotic leukocytes.
      RESULTS: Follicular cells aspirated from coasted patients showed a ratio in
      favour of apoptosis, especially in smaller follicles (48 versus 26%, P < 0.05).
      Follicular fluid determinations confirmed that coasting reduces VEGF protein
      secretion (1413 versus 3538 pg/ml, P < 0.001) and gene expression (2-fold
      decrease) in granulosa cells. Follicular fluid VEGF protein levels positively
      correlated with follicular size (r = 0.594, P = 0.001) and estradiol production
      (r = 0.558, P = 0.038). Women who underwent coasting showed a comparable IVF
      cycle outcome; however, a higher cancellation rate was found in cycles that were
      coasted. CONCLUSIONS: Coasting affects all follicles through apoptosis,
      especially immature follicles, without affecting oocyte/endometrial quality. The
      significant decrease found in VEGF expression and secretion explains why coasting
      is clinically effective in reducing the incidence and severity of OHSS.

PMID- 15155607
TI  - Vaginal misoprostol for cervical ripening before operative hysteroscopy in pre
      menopausal women: a double-blind, placebo-controlled trial with three dose
      regimens.
AB  - BACKGROUND: To evaluate the effects of vaginal misoprostol on cervical dilatation
      before operative hysteroscopy in pre-menopausal women. METHODS: Four groups of 12
      women were randomly assigned to receive either placebo or vaginal misoprostol in
      doses of 200, 400 or 800 micro g 4 h before the surgical procedure. The number of
      patients was calculated with an alpha = 0.01 and beta =0.20 for a difference of
      50%. The primary outcome measure was cervical width, assessed by the largest size
      of Hegar dilator that could be inserted without resistance. The secondary
      outcomes were subjective assessments of the ease of dilatation and pre-operative
      pain, as well as adverse effects and complications. RESULTS: There was no
      difference in the baseline diameter of the cervical opening between the placebo
      group (6.1 +/- 1.4 cm) and the misoprostol groups (6.3 +/- 2.1 cm). The groups
      did not differ significantly in the time required for dilatation, ease of
      dilation, or the number of adverse effects. Pre-operative pain, evaluated by a
      pain scale, was greater in the treatment groups and was rated at 2.5 +/- 2.3 (P =
      0.015), 2.4 +/- 1.2 (P = 0.073) and 2.8 +/- 2.9 (P = 0.012) respectively for each
      increasing dose group. CONCLUSIONS: Vaginal misoprostol applied 4 h before
      operative hysteroscopy at three different doses did not reduce the need for
      cervical dilatation, did not facilitate hysteroscopic surgery, and increased pre
      operative pain.

PMID- 15155608
TI  - Coping with infertility: a body-mind group intervention programme for infertile
      couples.
AB  - BACKGROUND: The recognition of the distressing character of infertility diagnosis
      and treatment has led to the development of several psychosocial interventions
      for infertile couples. At the Leuven University Fertility Centre, a body-mind
      marital group intervention was developed to help infertile couples cope with the
      distress related to infertility. METHODS AND RESULTS: This treatment programme
      was originally adapted from a mind-body approach, but integrated concepts and
      techniques from body-oriented therapy, art therapy and multi-family group
      therapy. In this paper, the therapeutic foundations, treatment goals and
      practical implications of the mind-body marital group intervention are outlined.
      Further, the treatment procedure is explained in detail and illustrated by
      clinical vignettes. CONCLUSIONS: Although the first clinical impressions about
      the usefulness of the body-mind group programme in fertility clinics seem
      promising, further research is needed to assess its effectiveness.

PMID- 15155609
TI  - Model for immune responses to Mycobacterium avium subspecies paratuberculosis in
      cattle.

PMID- 15155611
TI  - Disassembly of F-actin cytoskeleton after interaction of Bacillus cereus with
      fully differentiated human intestinal Caco-2 cells.
AB  - In the present study, the role of direct procaryote-eucaryote interactions in the
      virulence of Bacillus cereus was investigated. As a model of human enterocytes,
      differentiated Caco-2 cells were used. Infection of fully differentiated Caco-2
      cells with B. cereus in the exponential phase of growth, in order to minimize the
      concentration of spores or sporulating microorganisms, shows that a strain
      dependent cytopathic effect develops. Interestingly, addition of 3-h-old cultures
      of some strains resulted in complete detachment of the cultured cells after a 3-h
      infection whereas no such effect was found after a 3-h infection with 16-h-old
      cultures. Infection of enterocyte-like cells with B. cereus leads to disruption
      of the F-actin network and necrosis. Even though the effect of secreted factors
      cannot be ruled out, direct eucaryote-procaryote interaction seems to be
      necessary. In addition, we observed that some B. cereus strains were able to be
      internalized in Caco-2 cells. Our findings add a new insight into the mechanisms
      of virulence of B. cereus in the context of intestinal infection.

PMID- 15155610
TI  - Predominant outer membrane antigens of Bartonella henselae.
AB  - A hallmark of Bartonella henselae is persistent bacteremia in cats despite the
      presence of a vigorous host immune response. To understand better the long-term
      survival of B. henselae in cats, we examined the feline humoral immune response
      to B. henselae outer membrane (OM) proteins in naturally and experimentally
      infected cats. Initially, a panel of sera (n = 42) collected throughout North
      America from naturally infected cats was used to probe B. henselae total
      membranes to detect commonly recognized antigens. Twelve antigens reacted with
      sera from at least 85% of cats, and five were recognized by sera from all cats.
      To localize these antigens further, OMs were purified on discontinuous sucrose
      density step gradients. Each membrane fraction (OM, hybrid or inner membrane
      [IM]) contained less than 1% of the total malate dehydrogenase activity (soluble
      marker), indicating very little contamination by cytoplasmic proteins. FtsI, an
      integral IM cell division protein, was used to identify the low-density fraction
      (rho = 1.13 g/cm3) as putative IM (<5% of the total FtsI localized to the high
      density fraction) while lipopolysaccharide (LPS) and Pap31, a homolog of the
      Bartonella quintana heme-binding protein A (HbpA), defined the high-density
      fraction (rho = 1.20 g/cm3) as putative OM. Additionally, little evidence of
      cross-contamination between the IM and OM was evident by two-dimensional gel
      electrophoresis. When purified OMs were probed with feline sera, antigenic
      proteins profiles were very similar to those observed with total membranes,
      indicating that many, but not all, of the immunoreactive proteins detected in the
      initial immunoblots were OM components. Interestingly, two-dimensional
      immunoblots indicated that B. henselae LPS and members of the Hbp family of
      proteins did not appear to stimulate an humoral response in any infected cats.
      Seven proteins were recognized by at least 70% of sera tested, but only three
      were recognized by all sera. Nanospray-tandem mass spectrometry was used to
      identify OM components, including the immunodominant OM proteins. Recognition of
      the nonimmunogenic nature of the major OM components, such as LPS, and
      identification of the predominant immunogens should elucidate the mechanisms by
      which B. henselae establishes persistent bacteremic infections within cats.
      Additionally, the common antigens may serve as potential feline vaccine
      candidates to eliminate the pathogen from its animal reservoir.

PMID- 15155612
TI  - Experimental pneumococcal meningitis: impaired clearance of bacteria from the
      blood due to increased apoptosis in the spleen in Bcl-2-deficient mice.
AB  - Necrotic and apoptotic neuronal cell death can be found in pneumococcal
      meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in
      pneumococcal meningitis using Bcl-2 knockout (Bcl-2(-/-)) mice. By using a model
      of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient
      mice and control littermates were assessed by clinical score and a tight rope
      test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the
      bacterial titers in blood, spleen, and cerebellar homogenates were determined,
      and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice
      developed more severe clinical illness, and there were significant differences in
      the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h.
      The bacterial titers in the blood were greater in Bcl-2-deficient mice than in
      the controls (7.46 +/- 1.93 log CFU/ml versus 5.16 +/- 0.96 log CFU/ml [mean +/-
      standard deviation]; P < 0.01). Neuronal damage was most prominent in the
      hippocampal formation, but there were no significant differences between groups.
      In situ tailing revealed only a few apoptotic neurons in the brain. In the
      spleen, however, there were significantly more apoptotic leukocytes in Bcl-2
      deficient mice than in controls (5,148 +/- 3,406 leukocytes/mm2 versus 1,070 +/-
      395 leukocytes/mm2; P < 0.005). Bcl-2 appears to counteract sepsis-induced
      apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from
      the blood.

PMID- 15155613
TI  - Degeneration and regeneration of murine skeletal neuromuscular junctions after
      intramuscular injection with a sublethal dose of Clostridium sordellii lethal
      toxin.
AB  - Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the
      bacteria's major virulence factor, belongs to a family of large clostridial
      cytotoxins which glucosylate small GTP-binding proteins. Here, we report the
      results of our ex vivo analysis of the structure and function of skeletal
      neuromuscular tissue obtained from mice at various times after intramuscular
      injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused,
      within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and
      degeneration of skeletal muscle fibers in the injected area, and it glucosylated
      the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident
      6 to 9 days postinjury and was completed by 60 days. The expression of
      dystrophin, laminin, and fast and neonatal myosin in regenerating fibers,
      detected by immunofluorescence microscopy, confirmed that LT does not impair the
      high regenerative capacity of murine skeletal muscle fibers. Functional studies
      revealed that LT affects muscle contractility and neuromuscular transmission.
      However, partial recovery of nerve-evoked muscle twitches and tetanic
      contractions was observed by day 15 postinjection, and extensive remodeling of
      the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine
      receptors was still evident 30 days postinjection. In conclusion, to the best of
      our knowledge, this is the first report to characterize the degeneration and
      regeneration of skeletal neuromuscular tissue after in vivo exposure to a large
      clostridial cytotoxin. In addition, our data may provide an explanation for the
      severe neuromuscular alterations accompanying wound infections caused by C.
      sordellii.

PMID- 15155614
TI  - Interleukin-10 limits local and body cavity inflammation during infection with
      muscle-stage Trichinella spiralis.
AB  - The aim of this study was to characterize cellular responses to muscle-stage
      Trichinella spiralis. From its intracellular habitat in muscle, T. spiralis
      secretes potent glycoprotein antigens that elicit a strong systemic host immune
      response. Despite the magnitude and prolonged nature of this response, nurse
      cells are rarely destroyed by infiltrating cells. We tested the hypothesis that
      the anti-inflammatory cytokine interleukin-10 (IL-10) moderates cellular
      responses to muscle-stage parasites. Trichinella larvae colonize the diaphragm in
      large numbers, prompting us to evaluate regional responses in body cavities in
      addition to local responses in muscle. Mice deficient in IL-10 demonstrated an
      exaggerated inflammatory response around nurse cells and in the pleural cavity.
      The effect of IL-10 was most evident 20 days following muscle infection. The
      increased intensity of the response in IL-10-deficient mice did not affect
      parasite establishment or survival. Between 20 and 50 days postinfection, the
      inflammatory response was diminished in both wild-type and IL-10-deficient mice.
      Muscle infection also elicited an antibody response, characterized initially by
      mixed isotypes directed at somatic larval antigens and changing to an
      immunoglobulin G1-dominated response directed at tyvelose-bearing excreted or
      secreted antigens. We conclude that IL-10 limits local and regional inflammation
      during the early stages of muscle infection but that chronic inflammation is
      controlled by an IL-10-independent mechanism that is coincident with a Th2
      response.

PMID- 15155615
TI  - Borrelia burgdorferi binds to, invades, and colonizes native type I collagen
      lattices.
AB  - Borrelia burgdorferi binds strongly to the extracellular matrix and cells of the
      connective tissue, a binding apparently mediated by specific proteins and
      proteoglycans. We investigated the interactions between B. burgdorferi cells and
      intact type I collagen using hydrated lattices that reproduce features of in vivo
      collagen matrices. B. burgdorferi cells of several strains adhered avidly to
      these acellular matrices by a mechanism that was not mediated by decorin or other
      proteoglycans. Moreover, following adhesion to these matrices, B. burgdorferi
      grew and formed microcolonies. The collagen used in these studies was confirmed
      to lack decorin by immunoblot analysis; B. burgdorferi cells lacking the decorin
      adhesin bound readily to intact collagen matrices. B. burgdorferi also bound to
      collagen lattices that incorporated enzymes that degraded glycosaminoglycan
      chains in any residual proteoglycans. Binding of the bacteria to intact collagen
      was nonetheless specific, as bacteria did not bind agar and showed only minimal
      binding to bovine serum albumin, gelatin, pepsinized type I collagen, and intact
      collagen that had been misassembled under nonphysiological pH and ionic-strength
      conditions. Proteinase K treatment of B. burgdorferi cells decreased the binding,
      as did a lack of flagella, suggesting that surface-exposed proteins and motility
      may be involved in the ability of B. burgdorferi to interact with intact collagen
      matrices. The high efficiency of binding of B. burgdorferi strains to intact
      collagen matrices permits replacement of the commonly used isotopic binding assay
      with visual fluorescent microscopic assays and will facilitate future studies of
      these interactions.

PMID- 15155616
TI  - Pneumocystis activates human alveolar macrophage NF-kappaB signaling through
      mannose receptors.
AB  - Alveolar macrophages (AM) represent important effector cells in the innate immune
      response to the AIDS-related pathogen Pneumocystis, but the early AM host defense
      signaling events are poorly defined. Using AM from healthy individuals, we showed
      in the present study that Pneumocystis organisms stimulate AM NF-kappaB p50 and
      p65 nuclear translocation in a time-dependent and multiplicity-of-infection
      dependent manner as determined by electrophoretic mobility shift assay and
      immunofluorescence microscopy and that NF-kappaB nuclear translocation is
      associated with I-kappaB phosphorylation. Importantly, competitive inhibition of
      mannose receptor and targeted short interfering RNA-mediated gene suppression of
      mannose receptor mRNA and protein is associated with complete elimination of NF
      kappaB nuclear translocation in response to Pneumocystis. Furthermore, human
      immunodeficiency virus (HIV) infection of AM (as a model human disease state of
      reduced AM mannose receptor expression and function) inhibits Pneumocystis
      mediated NF-kappaB nuclear translocation and is associated with reduced I-kappaB
      phosphorylation and reduced interleukin-8 (IL-8) release. In contrast, NF-kappaB
      nuclear translocation and IL-8 release in response to lipopolysaccharide are
      intact in AM from both healthy and HIV-infected individuals, indicating that the
      observed impairment is not a global disturbance of the NF-kappaB pathway. Thus,
      in addition to phagocytic and endocytic effector functions, the present study
      identifies mannose receptors as pattern recognition receptors capable of NF
      kappaB activation in response to infectious non-self challenge. AM mannose
      receptor-mediated NF-kappaB activation may represent an important mechanism of
      the host cell response to Pneumocystis, and altered NF-kappaB activation in the
      context of HIV infection may impair a critical innate immune signaling response
      and may contribute to pathogenesis of opportunistic lung infections.

PMID- 15155617
TI  - Comparative analysis of B- and T-cell epitopes of Mycobacterium leprae and
      Mycobacterium tuberculosis culture filtrate protein 10.
AB  - Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well
      characterized immunodominant 10-kDa protein antigen known to elicit a very potent
      early gamma interferon response in T cells from M. tuberculosis-infected mice and
      humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only
      40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and
      thus has the potential for development as a T- or B-cell reactive antigen for
      specific diagnosis of leprosy. Antisera raised in mice or rabbits against
      recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with
      homologous peptides from arrays of overlapping synthetic peptides, indicating
      that there was no detectable cross-reactivity at the antibody level. Sera from
      leprosy and tuberculosis patients were also specific for the homologous protein
      or peptides and showed distinct patterns of recognition for either M. leprae or
      M. tuberculosis CFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell
      hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a
      cross-reactive response against the N-terminal heterologous CFP-10 peptide, the
      region that exhibits the highest level of identity in the two proteins; however,
      the majority of peptide epitopes recognized by mouse T-cell hybridomas specific
      for each protein did not cross-react with heterologous peptides. Coupled with the
      human serology data, these results raise the possibility that peptides that could
      be used to differentiate infections caused by these two related microorganisms
      could be developed. Immunohistochemical staining of sections of M. leprae
      infected nude mouse footpads resulted in strongly positive staining in
      macrophages and dendritic cells, as well as weaker staining in extracellular
      areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis,
      is a secreted protein.

PMID- 15155618
TI  - Identification of acyloxyacyl hydrolase, a lipopolysaccharide-detoxifying enzyme,
      in the murine urinary tract.
AB  - Acyloxyacyl hydrolase (AOAH) is an unusual but highly conserved lipase,
      previously described only in myeloid cells, that removes secondary fatty acyl
      chains from bacterial lipopolysaccharides (LPS) and may also act on various
      glycero(phospho)lipids. Deacylation by AOAH greatly reduces the ability of LPS to
      stimulate cells via CD14-MD-2-Toll-like receptor 4. We report here that renal
      cortical tubule cells produce AOAH and secrete it into urine, where it can
      deacylate LPS. In vitro studies revealed that proximal tubule cells secrete pro
      AOAH, which can be taken up by bladder cells and processed to the heterodimeric,
      more enzymatically active, mature form of AOAH. AOAH can then be used by the
      recipient cells to deacylate LPS. The enzyme produced by proximal tubule
      epithelium may thus be shared with downstream cells. In addition, mature AOAH is
      found in the urine. We suggest that cortical tubule cells may produce and secrete
      AOAH to limit inflammatory responses to gram-negative bacteria throughout the
      urinary tract.

PMID- 15155619
TI  - Toll-like receptor 4 expression and cytokine responses in the human urinary tract
      mucosa.
AB  - Mucosal pathogens trigger a local innate host response by activating epithelial
      cells. Bacterial adherence and Toll-like receptor 4 (TLR4) signaling have been
      implicated as key events in this process. This study addressed the molecular
      basis of the epithelial response to gram-negative infection in the human urinary
      tract. Mucosal biopsies were obtained from kidneys, ureters, and bladders of
      patients undergoing urinary tract surgery, and epithelial TLR4 and CD14
      expression was examined by immunohistochemistry. TLR4 was detected in epithelial
      cells lining the entire urinary tract and in the renal tubular epithelium. CD14,
      in contrast, was completely absent from the epithelial tissue. The response of
      the epithelial cells to infection was studied by in vitro challenge of the
      biopsies with uropathogenic Escherichia coli bacteria. A rapid cytokine response
      was observed, with production of interleukin-1beta (IL-1beta), IL-6, and IL-8 but
      not of IL-4 or gamma interferon. Adhering, P- or type 1-fimbriated E. coli
      activated IL-6 and IL-8 production more efficiently than the nonfimbriated
      control, as shown by cellular staining and analysis of secreted cytokines. The
      results demonstrate that human uroepithelial cells possess the molecular
      machinery needed to respond to uropathogenic E. coli. This includes recognition
      receptors for fimbriae and TLR4 for transmembrane signaling. We speculate that
      the lack of membrane-bound CD14 allows the epithelium to regulate its sensitivity
      to lipopolysaccharide and to discriminate between more-virulent and less-virulent
      strains.

PMID- 15155620
TI  - Bacterial superantigen-treated intestinal epithelial cells upregulate heat shock
      proteins 25 and 72 and are resistant to oxidant cytotoxicity.
AB  - While the pathological events evoked by infection are commonly described,
      effective host responses to bacteria and their products should primarily be
      protective. Heat shock protein (Hsp) expression is upregulated by many stimuli
      and serves to maintain intracellular protein integrity. The ability of the
      prototypic superantigen, Staphylococcus aureus enterotoxin B (SEB) to induce Hsps
      was investigated with BALB/c mice and by in vitro addition to the murine small
      intestinal epithelial cell line MSIE. SEB-treated (5 or 100 microg
      intraperitoneally) mice revealed increased Hsp25 and Hsp72, but not Hsc73, in
      jejunal lymphocytes and epithelial cells. A similar Hsp response to SEB occurred
      in MSIE cells and was preceded by activation of the ERK1/2 and p38 mitogen
      activated protein kinases but not the SAPK/JNK pathway; pharmacological
      inhibition of ERK1/2, but not p38, significantly reduced SEB-induced Hsps.
      Moreover, SEB-treated MSIE cells were protected against oxidant-induced
      cytotoxicity (measured by 51Cr release) and F-actin depolymerization. Thus, SEB
      exposure results in a rapid induction of the Hsp25 and Hsp72 in intestinal
      epithelial cells, both directly and through lymphocyte activation, and we suggest
      that this event is important in protecting the gut from damage by Staphylococcus
      infection or in the reparatory process and may be a generalized response to lumen
      derived bacterial toxins.

PMID- 15155621
TI  - Myeloid differentiation antigen 88 deficiency impairs pathogen clearance but does
      not alter inflammation in Borrelia burgdorferi-infected mice.
AB  - The spirochete Borrelia burgdorferi causes acute inflammation in mice that
      resolves with the development of pathogen-specific adaptive immunity. B.
      burgdorferi lipoproteins activate innate immune cells via Toll-like receptor 2
      (TLR2), but TLR2-deficient mice are not resistant to B. burgdorferi-induced
      disease, suggesting the involvement of other TLRs or non-TLR mechanisms in the
      induction of acute inflammation. For this study, we used mice that were deficient
      in the intracellular adapter molecule myeloid differentiation antigen 88 (MyD88),
      which is required for all TLR-induced inflammatory responses, to determine
      whether the interruption of this pathway would alter B. burgdorferi-induced
      disease. Infected MyD88(-/-) mice developed carditis and arthritis, similar to
      the disease in wild-type (WT) mice analyzed at its peak (days 14 and 28) and
      during regression (day 45). MyD88(-/-) macrophages produced tumor necrosis factor
      alpha only when spirochetes were opsonized, suggesting a role for B. burgdorferi
      specific antibody in disease expression. MyD88(-/-) mice produced stronger
      pathogen-specific Th2-dependent immunoglobulin G1 (IgG1) responses than did WT
      mice, and their IgM titers remained significantly elevated through 90 days of
      infection. Despite specific antibodies, the pathogen burden was 250-fold higher
      in MyD88(-/-) mice than in WT mice 45 days after infection; by 90 days of
      infection, the pathogen burden had diminished substantially in MyD88(-/-) mice,
      but it was still elevated compared to that in WT mice. The elevated pathogen
      burden may be explained in part by the finding that MyD88(-/-) peritoneal
      macrophages could ingest spirochetes but degraded them more slowly than WT
      macrophages. Our results show that MyD88-dependent signaling pathways are not
      required for B. burgdorferi-induced inflammation but are necessary for the
      efficient control of the pathogen burden by phagocytes.

PMID- 15155622
TI  - Virulent and avirulent strains of Francisella tularensis prevent acidification
      and maturation of their phagosomes and escape into the cytoplasm in human
      macrophages.
AB  - Francisella tularensis, the agent of tularemia, is an intracellular pathogen, but
      little is known about the compartment in which it resides in human macrophages.
      We have examined the interaction of a recent virulent clinical isolate of F.
      tularensis subsp. tularensis and the live vaccine strain with human macrophages
      by immunoelectron and confocal immunofluorescence microscopy. We assessed the
      maturation of the F. tularensis phagosome by examining its acquisition of the
      lysosome-associated membrane glycoproteins (LAMPs) CD63 and LAMP1 and the acid
      hydrolase cathepsin D. Two to four hours after infection, vacuoles containing
      live F. tularensis cells acquired abundant staining for LAMPs but little or no
      staining for cathepsin D. However, after 4 h, the colocalization of LAMPs with
      live F. tularensis organisms declined dramatically. In contrast, vacuoles
      containing formalin-killed bacteria exhibited intense staining for all of these
      late endosomal/lysosomal markers at all time points examined (1 to 16 h). We
      examined the pH of the vacuoles 3 to 4 h after infection by quantitative
      immunogold staining and by fluorescence staining for lysosomotropic agents.
      Whereas phagosomes containing killed bacteria stained intensely for these agents,
      indicating a marked acidification of the phagosomes (pH 5.5), phagosomes
      containing live F. tularensis did not concentrate these markers and thus were not
      appreciably acidified (pH 6.7). An ultrastructural analysis of the F. tularensis
      compartment revealed that during the first 4 h after uptake, the majority of F.
      tularensis bacteria reside within phagosomes with identifiable membranes. The
      cytoplasmic side of the membranes of approximately 50% of these phagosomes was
      coated with densely staining fibrils of approximately 30 nm in length. In many
      cases, these coated phagosomal membranes appeared to bud, vesiculate, and
      fragment. By 8 h after infection, the majority of live F. tularensis bacteria
      lacked any ultrastructurally discernible membrane separating them from the host
      cell cytoplasm. These results indicate that F. tularensis initially enters a
      nonacidified phagosome with LAMPs but without cathepsin D and that the phagosomal
      membrane subsequently becomes morphologically disrupted, allowing the bacteria to
      gain direct access to the macrophagic cytoplasm. The capacity of F. tularensis to
      alter the maturation of its phagosome and to enter the cytoplasm is likely an
      important element of its capacity to parasitize macrophages and has major
      implications for vaccine development.

PMID- 15155623
TI  - Comparative analysis of EspF from enteropathogenic and enterohemorrhagic
      Escherichia coli in alteration of epithelial barrier function.
AB  - Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are
      related intestinal pathogens that harbor highly similar pathogenicity islands
      known as the locus of enterocyte effacement (LEE). Despite their genetic
      similarity, these two pathogens disrupt epithelial tight junction barrier
      function with distinct kinetics. EHEC-induced reduction in transepithelial
      electrical resistance (TER), a measure of barrier function disruption, is
      significantly slower and more modest in comparison to that induced by EPEC. The
      variation in bacterial adherence only partially accounted for these differences.
      The LEE-encoded effector protein EspF has been shown to be critical for EPEC
      induced alterations in TER. EspF from both EPEC and EHEC is expressed and
      secreted upon growth in tissue culture medium. The mutation of EHEC cesF
      suggested that the optimal expression and secretion of EHEC EspF required its
      chaperone CesF, as has been shown for EPEC. In contrast to EPEC espF and cesF,
      mutation of the corresponding EHEC homologs did not dramatically alter the
      decrease in TER. These differences could possibly be explained by the presence of
      additional espF-like sequences (designated U- and M-espF, where the letter
      designations refer to the specific cryptic prophage sequences on the EHEC
      chromosome closest to the respective genes) in EHEC. Reverse transcription-PCR
      analyses revealed coordinate regulation of EHEC U-espF and the LEE-encoded espF,
      with enhanced expression in bacteria grown in Dulbecco-Vogt modified Eagle's
      medium compared to bacteria grown in Luria broth. Both EHEC espF and U-espF
      complemented an EPEC espF deletion strain for barrier function alteration. The
      overexpression of U-espF, but not espF, in wild-type EHEC potentiated the TER
      response. These studies reveal further similarities and differences in the
      pathogenesis of EPEC and EHEC.

PMID- 15155624
TI  - Recombinant Streptococcus equi proteins protect mice in challenge experiments and
      induce immune response in horses.
AB  - Horses that have undergone infection caused by Streptococcus equi subspecies equi
      (strangles) were found to have significantly increased serum antibody titers
      against three previously characterized proteins, FNZ (cell surface-bound
      fibronectin binding protein), SFS (secreted fibronectin binding protein), and EAG
      (alpha2-macroglobulin, albumin, and immunoglobulin G [IgG] binding protein) from
      S. equi. To assess the protective efficacy of vaccination with these three
      proteins, a mouse model of equine strangles was utilized. Parts of the three
      recombinant proteins were used to immunize mice, either subcutaneously or
      intranasally, prior to nasal challenge with S. equi subsp. equi. The adjuvant
      used was EtxB, a recombinant form of the B subunit of Escherichia coli heat
      labile enterotoxin. It was shown that nasal colonization of S. equi subsp. equi
      and weight loss due to infection were significantly reduced after vaccination
      compared with a mock-vaccinated control group. This effect was more pronounced
      after intranasal vaccination than after subcutaneous vaccination; nearly complete
      eradication of nasal colonization was obtained after intranasal vaccination (P <
      0.001). When the same antigens were administered both intranasally and
      subcutaneously to healthy horses, significant mucosal IgA and serum IgG antibody
      responses against FNZ and EAG were obtained. The antibody response was enhanced
      when EtxB was used as an adjuvant. No adverse effects of the antigens or EtxB
      were observed. Thus, FNZ and EAG in conjunction with EtxB are promising
      candidates for an efficacious and safe vaccine against strangles.

PMID- 15155625
TI  - Role of flagellin and the two-component CheA/CheY system of Listeria
      monocytogenes in host cell invasion and virulence.
AB  - The flagellum protein flagellin of Listeria monocytogenes is encoded by the flaA
      gene. Immediately downstream of flaA, two genes, cheY and cheA, encoding products
      with homology to chemotaxis proteins of other bacteria, are located. In this
      study we constructed deletion mutants with mutations in flaA. cheY, and cheA to
      elucidate their role in the biology of infection with L. monocytogenes. The
      DeltacheY, DeltacheA, and double-mutant DeltacheYA mutants, but not DeltaflaA
      mutant, were motile in liquid media. However, the DeltacheA mutant had impaired
      swarming and the DeltacheY and DeltacheYA mutants were unable to swarm on soft
      agar plates, suggesting that cheY and cheA genes encode proteins involved in
      chemotaxis. The DeltaflaA, DeltacheY, DeltacheA, and DeltacheYA mutants (grown at
      24 degrees C) showed reduced association with and invasion of Caco-2 cells
      compared to the wild-type strain. However, spleens from intragastrically infected
      BALB/c and C57BL/6 mice showed larger and similar numbers of the DeltaflaA and
      DeltacheYA mutants, respectively, compared to the wild-type controls. Such a
      discrepancy could be explained by the fact that tumor necrosis factor receptor
      p55 deficient mice showed dramatically exacerbated susceptibility to the wild
      type but unchanged or only slightly increased levels of the DeltaflaA or
      DeltacheYA mutant. In summary, we show that listerial flaA. cheY, and cheA gene
      products facilitate the initial contact with epithelial cells and contribute to
      effective invasion but that flaA could also be involved in the triggering of
      immune responses.

PMID- 15155626
TI  - Induction of morphological and electrophysiological changes in hamster cornea
      after in vitro interaction with trophozoites of Acanthamoeba spp.
AB  - Acanthamoeba castellani and Acanthamoeba polyphaga are free-living amebae that
      cause keratitis and granulomatous encephalitis in humans. We have analyzed the
      early morphological and electrophysiological changes occurring during the in
      vitro interaction of cultured amebae with intact or physically damaged corneas
      obtained from hamsters. Both species of Acanthamoeba produced similar cytopathic
      changes, as seen by light microscopy and scanning electron microscopy. After
      adhesion to the epithelial surface, trophozoites formed clumps and migrated
      toward the cell borders, causing the separation of adjacent cells at 1 h of
      coculture. At later stages (2 to 4 h), some amebae were found under desquamating
      epithelial cells whereas others were seen associated with damaged cells or
      forming amebostome-like structures to ingest detached epithelial cells. Control
      corneas incubated in culture medium conditioned with amebae showed a cytoplasmic
      vacuolization and blurring of the epithelial-stromal junction. The early stages
      of corneal epithelial damage caused by amebae were also analyzed by measuring the
      transepithelial resistance changes in corneas mounted in Ussing chambers. Both
      species of Acanthamoeba caused a rapid decrease in electrical resistance. The
      present observations demonstrate that under in vitro conditions, Acanthamoeba
      trophozoites rapidly cause significant damage to the corneal epithelium.
      Furthermore, in our experimental model, previous physical damage to the corneas
      was not a prerequisite for the development of amebic corneal ulcerations.

PMID- 15155627
TI  - Therapeutic vaccination against Helicobacter pylori in the beagle dog
      experimental model: safety, immunogenicity, and efficacy.
AB  - Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric
      mucosa causing gastritis and peptic ulcer and increasing the risk of gastric
      cancer. The efficacy of current antibiotic-based therapies can be limited by
      problems of patient compliance and increasing antibiotic resistance; the vaccine
      approach can overcome these limits. The present study describes the therapeutic
      vaccination of experimentally H. pylori-infected beagle dogs, an animal model
      that reproduces several aspects of the human infection with H. pylori. The
      vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP,
      formulated at different doses (10, 25, or 50 microg each) with alum and
      administered intramuscularly either weekly or monthly. No adverse effects were
      observed after vaccination and a good immunoglobulin G response was generated
      against each of the three antigens. Bacterial colonization and gastritis were
      decreased after the completion of the vaccination cycle, especially in the case
      of the monthly immunization schedule. In conclusion, therapeutic vaccination in
      the beagle dog model was safe and immunogenic and was able to limit H. pylori
      colonization and the related gastric pathology.

PMID- 15155628
TI  - Lipopolysaccharide protects primary B lymphocytes from apoptosis by preventing
      mitochondrial dysfunction and bax translocation to mitochondria.
AB  - Mature B lymphocytes undergo apoptosis when they are cultured in the absence of
      survival factors. Gram-negative bacterial lipopolysaccharide (LPS) prevents this
      spontaneous apoptosis. This study aimed to better define the signaling pathway(s)
      involved in the antiapoptotic activity of this endotoxin. We report here that, in
      addition to its effects on spontaneous apoptosis, LPS protects B cells from
      apoptosis induced by the broad-spectrum protein kinase inhibitor staurosporine.
      LPS increased cell viability and concomitantly maintained the mitochondrial
      transmembrane potential (DeltaPsim) and high glutathione levels. Moreover, LPS
      inhibited cytosolic cytochrome c release and decreased caspase-9 activation.
      Unlike staurosporine, LPS induced the retention of Bax, a proapoptotic protein of
      the Bcl-2 family, in the cytosol by preventing its translocation to mitochondria.
      These results suggest that Bax relocalization from the cytosol to the
      mitochondria is an important step of mature B-cell apoptosis and that the
      antiapoptotic activity of LPS occurs upstream of mitochondrial events.

PMID- 15155629
TI  - Binding and internalization of Clostridium perfringens iota-toxin in lipid rafts.
AB  - Clostridium perfringens iota-toxin is a binary toxin composed of an enzymatic
      component (Ia) and a binding component (Ib). The oligomer of Ib formed in
      membranes induces endocytosis. We examined the binding and internalization of Ib
      by using Cy3-labeled Ib. Labeled Ib was retained at the membranes of MDCK cells
      for 60 min of incubation at 37 degrees C, and later it was detected in
      cytoplasmic vesicles. To determine whether Ib associates with lipid rafts, we
      incubated MDCK cells with Ib at 4 or 37 degrees C and fractionated the Triton
      insoluble membranes. An Ib complex of 500 kDa was localized at 37 degrees C to
      the insoluble fractions that fulfilled the criteria of lipid rafts, but it did
      not form at 4 degrees C. The amount of complex in the raft fraction reached a
      maximum after 60 min of incubation at 37 degrees C. When the cells that were
      preincubated with Ib at 4 degrees C were incubated at 37 degrees C, the complex
      was detected in the raft fraction. The treatment of MDCK cells with methyl-beta
      cyclodextrin reduced the localization of the Ib complex to the rafts and the
      rounding of the cells induced by Ia plus Ib. When 125I-labeled Ia was incubated
      with the cells in the presence of Ib at 37 degrees C, it was localized in the
      raft fraction. Surface plasmon resonance analysis revealed that Ia binds to the
      oligomer of Ib. We conclude that Ib binds to a receptor in membranes and then
      moves to rafts and that Ia bound to the oligomer of Ib formed in the rafts is
      internalized.

PMID- 15155630
TI  - Enhancement of anthrax lethal toxin cytotoxicity: a subset of monoclonal
      antibodies against protective antigen increases lethal toxin-mediated killing of
      murine macrophages.
AB  - We investigated the ability of using monoclonal antibodies (MAbs) against anthrax
      protective antigen (PA), an anthrax exotoxin component, to modulate exotoxin
      cytotoxic activity on target macrophage cell lines. Anthrax PA plays a critical
      role in the pathogenesis of Bacillus anthracis infection. PA is the cell-binding
      component of the two anthrax exotoxins: lethal toxin (LeTx) and edema toxin.
      Several MAbs that bind the PA component of LeTx are known to neutralize LeTx
      mediated killing of target macrophages. Here we describe for the first time an
      overlooked population of anti-PA MAbs that, in contrast, function to increase the
      potency of LeTx against murine macrophage cell lines. The results support a
      possible mechanism of enhancement: binding of MAb to PA on the macrophage cell
      surface stabilizes the PA by interaction of MAb with macrophage Fcgamma
      receptors. This results in an increase in the amount of PA bound to the cell
      surface, which in turn leads to an enhancement in cell killing, most likely due
      to increased internalization of LF. Blocking of PA-receptor binding eliminates
      enhancement by MAb, demonstrating the importance of this step for the observed
      enhancement. The additional significance of these results is that, at least in
      mice, immunization with PA appears to elicit a poly-clonal response that has a
      significant prevalence of MAbs that enhance LeTx-mediated killing in macrophages.

PMID- 15155631
TI  - The LetE protein enhances expression of multiple LetA/LetS-dependent transmission
      traits by Legionella pneumophila.
AB  - Legionella pneumophila colonizes freshwater amoebae and can also replicate within
      alveolar macrophages. When their nutrient supply is exhausted, replicating
      bacteria become cytotoxic, motile, and infectious, which is thought to promote
      transmission to a new amoeba. The differentiation of L. pneumophila is
      coordinated by the sigma factors RpoS and FliA and the two-component regulator
      LetA/LetS and is enhanced by the letE locus. Here we demonstrate that letE
      promotes motility by increasing expression of the flagellin gene flaA but has
      little impact on the transcription of fliA, the flagellar sigma factor gene. In
      addition to promoting motility, letE induces the characteristic shape, pigment,
      and heat resistance of stationary-phase L. pneumophila. To gain insight into how
      letE promotes the expression of the transmission phenotype, we designed molecular
      genetic experiments to discriminate between the following three models: letE
      mutations are polar on milX; letE encodes a small novel protein; or, by analogy
      to csrB, letE encodes a regulatory RNA that sequesters CsrA to relieve
      repression. We report that letE encodes an activator protein, as it does not
      complement an Escherichia coli csrB mutant, it directs the synthesis of an
      approximately 12-kDa polypeptide, and a letE nonsense mutation eliminates
      function. A monocistronic letE RNA is abundant during the exponential phase, and
      its decay during the stationary phase requires RpoS and LetA/LetS. We also
      discuss how the LetE protein may interact with LetA/LetS and CsrA to enhance L.
      pneumophila differentiation to a transmissible form.

PMID- 15155632
TI  - Tyrosine kinase inhibition reduces inflammation in the acute stage of
      experimental pneumococcal meningitis.
AB  - Bacterial meningitis is an acute inflammatory disease of the central nervous
      system with a mortality rate of up to 30%. Excessive stimulation of the host
      immune system by bacterial surface components contributes to this devastating
      outcome. In vitro studies have shown that protein tyrosine kinase inhibitors are
      highly effective in preventing the release of proinflammatory cytokines induced
      by pneumococcal cell walls in microglia. In a well-established rat model,
      intracisternal injection of purified pneumococcal cell walls induced meningitis
      characterized by increases in the regional cerebral blood flow and intracranial
      pressure, an influx of leukocytes, and high concentrations of tumor necrosis
      factor alpha (TNF-alpha) in the cerebrospinal fluid. Compared with the values at
      the beginning of the experiment, intraperitoneal injection of tyrphostin AG 126
      reduced the increases in regional cerebral blood flow (at 6 h, 127% +/- 14%
      versus 222% +/- 51% of the baseline value; P < 0.05) and intracranial pressure
      (at 6 h, 0.8 +/- 2.4 versus 5.4 +/- 2.0 mm of Hg; P < 0.05), the influx of
      leukocytes (at 6 h, 1,336 +/- 737 versus 4,350 +/- 2,182 leukocytes/microl; P <
      0.05), and the TNF-alpha concentration (at 6 h, 261 +/- 188 versus 873 +/- 135
      pg/microl; P < 0.05). These results demonstrate that inhibition of AG 126
      sensitive tyrosine kinase pathways may provide new approaches for preventing
      excessive inflammation and reducing the increases in blood flow and intracranial
      pressure in the acute phase of bacterial meningitis.

PMID- 15155633
TI  - Bacterial probiotic modulation of dendritic cells.
AB  - Intestinal dendritic cells are continually exposed to ingested microorganisms and
      high concentrations of endogenous bacterial flora. These cells can be activated
      by infectious agents and other stimuli to induce T-cell responses and to produce
      chemokines which recruit other cells to the local environment. Bacterial
      probiotics are of increasing use against intestinal disorders such as
      inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to
      regain immunologic quiescence. This study was designed to determine the ability
      of a bacterial probiotic cocktail VSL#3 to alter cell surface antigen expression
      and cytokine production in bone marrow-derived dendritic cell-enriched
      populations. Cell surface phenotype was monitored by monoclonal fluorescent
      antibody staining, and cytokine levels were quantitated by enzyme-linked
      immunosorbent assay. High-dose probiotic upregulated the expression of C80, CD86,
      CD40, and major histocompatibility complex class II I-Ad. Neither B7-DC or B7RP-1
      was augmented after low-dose probiotic or Lactobacillus casei treatment, but B7RP
      1 showed increased expression on dendritic cells stimulated with the gram
      negative bacterium Escherichia coli. Functional studies showed that probiotic did
      not enhance the ability of dendritic cells to induce allogeneic T-cell
      proliferation, as was observed for E. coli. Substantial enhancement of
      interleukin-10 release was observed in dendritic cell-enriched culture
      supernatants after 3 days of probiotic stimulation. These results demonstrate
      that probiotics possess the ability to modulate dendritic cell surface phenotype
      and cytokine release in granulocyte-macrophage colony-stimulating factor
      stimulated bone marrow-derived dendritic cells. Regulation of dendritic cell
      cytokines by probiotics may contribute to the benefit of these molecules in
      treatment of intestinal diseases.

PMID- 15155634
TI  - Cystathionine beta-lyase is important for virulence of Salmonella enterica
      serovar Typhimurium.
AB  - The biosynthesis of methionine in bacteria requires the mobilization of sulfur
      from Cys by the formation and degradation of cystathionine. Cystathionine beta
      lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe,
      catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in
      methionine biosynthesis. This enzyme has been suggested to be the target for
      pyridinamine antimicrobial agents. We have demonstrated, by using purified
      enzymes from bacteria and yeast, that cystathionine beta-lyase is not the likely
      target of these agents. Nonetheless, an insertional inactivation of metC in
      Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence
      in a mouse model of systemic infection. This result confirms a previous chemical
      validation of the Met biosynthetic pathway as a target for the development of
      antibacterial agents and demonstrates that cystathionine beta-lyase is important
      for bacterial virulence.

PMID- 15155636
TI  - Associations between responses to the rhoptry-associated membrane antigen of
      Plasmodium falciparum and immunity to malaria infection.
AB  - Rhoptry proteins participate in the invasion of red blood cells by merozoites
      during the malaria parasite's asexual-stage cycle. Interference with the rhoptry
      protein function has been shown to prevent invasion, and three rhoptry proteins
      have been suggested as potential components of a vaccine against malaria. Rhoptry
      associated membrane antigen (RAMA) is a 170-kDa protein of Plasmodium falciparum
      which is processed to a 60-kDa mature form in the rhoptries. p60/RAMA is
      discharged from rhoptries of free merozoites and binds to the red-cell membrane
      before being internalized to form part of the parasitophorous vacuole of the
      newly developing ring. We examined the range of anti-RAMA responses in
      individuals living in an area of endemicity for malaria and determined its
      association with clinical immunity. RAMA is immunogenic during infections, and at
      least three epitopes within RAMA are recognized by hyperimmune sera in
      immunoblots. Sera from individuals living in a region of Vietnam where malaria is
      endemic possessed strong antibody responses toward two C-terminal regions of
      RAMA. Cytophilic antibody isotypes (immunoglobulin G1 [IgG1] and IgG3)
      predominated in humoral responses to both C-terminal epitopes. Acute episodes of
      P. falciparum infection result in significant boosting of levels of antibody to
      an epitope at the extreme C terminus of RAMA that harbors the red-cell-binding
      domain. Immunity to P. falciparum infection was linked to elevated levels of IgG3
      responses to this functional domain of RAMA, suggesting that the region may
      contain a protective epitope useful for inclusion in a multiepitope vaccine
      against malaria.

PMID- 15155635
TI  - Clearance of Citrobacter rodentium requires B cells but not secretory
      immunoglobulin A (IgA) or IgM antibodies.
AB  - Citrobacter rodentium, a murine model pathogen for human enteropathogenic
      Escherichia coli, predominantly colonizes the lumen and mucosal surface of the
      colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice
      infected with C. rodentium develop a secretory immunoglobulin A (IgA) response,
      but the role of B cells or secretory antibodies in host defense is unknown. To
      address this question, we conducted oral C. rodentium infections in mice lacking
      B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice
      showed peak bacterial numbers in colon and feces at 1 week and bacterial
      eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible
      initially but could not control infection subsequently. Tissue responses showed
      marked differences, as infection of normal mice was accompanied by transient
      crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6
      weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but
      severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6
      weeks. The functions of B cells were not mediated by secretory antibodies, since
      mice lacking IgA or secreted IgM or proteins required for their transport into
      the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic
      administration of immune sera reduced bacterial numbers significantly in normal
      and pIgR-deficient mice, and depletion of IgG abrogated this effect. These
      results indicate that host defense against C. rodentium depends on B cells and
      IgG antibodies but does not require production or transepithelial transport of
      IgA or secreted IgM.

PMID- 15155637
TI  - Age-specific immunoglobulin g (IgG) and IgA to pneumococcal protein antigens in a
      population in coastal kenya.
AB  - Streptococcus pneumoniae is the primary etiological agent of community-acquired
      pneumonia and a major cause of meningitis and bacteremia. Three conserved
      pneumococcal proteins-pneumolysin, pneumococcal surface adhesin A (PsaA), and
      pneumococcal surface protein A (PspA)-are currently being investigated as vaccine
      candidates. Such protein-based vaccines, if proven effective, could provide a
      cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan
      Africa exist concerning the development of natural antibody to these antigens,
      however. To investigate the age-specific development of antiprotein
      immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2
      weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked
      immunosorbent assays. IgG and IgA antibody responses to each antigen were
      observed in all age groups. Serum concentrations of IgG and IgA antibody
      responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but
      not to PsaA, increased significantly with age (P < 0.001). No decline was
      observed in the sera of the elderly. Anti-protein IgG concentrations were only
      weakly correlated (0.30 < r < 0.56; P < 0.0001), as were IgA concentrations (0.24
      < r < 0.54; P < 0.0001).

PMID- 15155638
TI  - Recombinant Mycobacterium bovis BCG expressing the Sm14 antigen of Schistosoma
      mansoni protects mice from cercarial challenge.
AB  - The Sm14 antigen of Schistosoma mansoni was cloned and expressed in Mycobacterium
      bovis BCG as a fusion with the Mycobacterium fortuitum beta-lactamase protein
      under the control of its promoter, pBlaF*; the protein was localized in the
      bacterial cell wall. The rBCG-Sm14 strain was shown to be relatively stable in
      cultured murine and bovine monocytes in terms of infectivity, bacterial
      persistence, and plasmid stability. The immunization of mice with rBCG-Sm14
      showed no induction of anti-Sm14 antibodies; however, splenocytes of immunized
      mice released increased levels of gamma interferon upon stimulation with
      recombinant Sm14 (rSm14), indicating an induction of a Th1-predominant cellular
      response against Sm14. Mice immunized with one or two doses of rBCG-Sm14 and
      challenged with live S. mansoni cercaria showed a 48% reduction in worm burden,
      which was comparable to that obtained by immunization with three doses of rSm14
      purified from Escherichia coli. The data presented here further enhance the
      status of Sm14 as a promising candidate antigen for the control of
      schistosomiasis and indicate that a one-dose regimen of rBCG-Sm14 could be
      considered a convenient means to overcome many of the practical problems
      associated with the successful implementation of a multiple-dose vaccine schedule
      in developing countries.

PMID- 15155639
TI  - Complement activation and complement-dependent inflammation by Neisseria
      meningitidis are independent of lipopolysaccharide.
AB  - Fulminant meningococcal sepsis has been termed the prototypical
      lipopolysaccharide (LPS)-mediated gram-negative septic shock. Systemic
      inflammation by activated complement and cytokines is important in the
      pathogenesis of this disease. We investigated the involvement of meningococcal
      LPS in complement activation, complement-dependent inflammatory effects, and
      cytokine or chemokine production. Whole blood anticoagulated with lepirudin was
      stimulated with wild-type Neisseria meningitidis H44/76 (LPS+), LPS-deficient N.
      meningitidis H44/76lpxA (LPS-), or purified meningococcal LPS (NmLPS) at
      concentrations that were relevant to meningococcal sepsis. Complement activation
      products, chemokines, and cytokines were measured by enzyme-linked immunosorbent
      assays, and granulocyte CR3 (CD11b/CD18) upregulation and oxidative burst were
      measured by flow cytometry. The LPS+ and LPS- N. meningitidis strains both
      activated complement effectively and to comparable extents. Purified NmLPS, used
      at a concentration matched to the amount present in whole bacteria, did not
      induce any complement activation. Both CR3 upregulation and oxidative burst were
      also induced, independent of LPS. Interleukin-1beta (IL-1beta), tumor necrosis
      factor alpha, and macrophage inflammatory protein 1alpha production was
      predominantly dependent on LPS, in contrast to IL-8 production, which was also
      markedly induced by the LPS- meningococci. In this whole blood model of
      meningococcal sepsis, complement activation and the immediate complement
      dependent inflammatory effects of CR3 upregulation and oxidative burst occurred
      independent of LPS.

PMID- 15155640
TI  - Suppression of serum antibody responses by pertussis toxin after respiratory
      tract colonization by Bordetella pertussis and identification of an
      immunodominant lipoprotein.
AB  - Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis,
      contributes to respiratory tract infection and disease caused by this pathogen.
      By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in
      frame deletion of the ptx genes encoding PT (DeltaPT), we recently found that the
      lack of PT confers a significant defect in respiratory tract colonization in mice
      after intranasal inoculation. In this study, we analyzed serum antibody responses
      in mice infected with the WT or DeltaPT strain and found that infection with the
      DeltaPT strain elicited greater responses to several B. pertussis antigens than
      did infection with the WT, despite the lower colonization level achieved by the
      DeltaPT strain. The same enhanced antibody response was observed after infection
      with a strain expressing an enzymatically inactive PT; but this response was not
      observed after infection with B. pertussis mutant strains lacking filamentous
      hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered
      with the DeltaPT inoculum, indicating a specific role for PT activity in this
      immunosuppressive effect. In particular, there were consistent strong serum
      antibody responses to one or more low-molecular-weight antigens after infection
      with the DeltaPT strain. These antigens were Bvg independent, membrane localized,
      and also expressed by the closely related pathogens Bordetella parapertussis and
      Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass
      spectrometry were used to identify one of the immunodominant low-molecular-weight
      antigens as a protein with significant sequence homology to peptidoglycan
      associated lipoprotein in several other gram-negative bacterial species. However,
      a serum antibody response to this protein alone did not protect mice against
      respiratory tract infection by B. pertussis.

PMID- 15155641
TI  - Cryptococcus neoformans capsule structure evolution in vitro and during murine
      infection.
AB  - Cryptococcus neoformans capsule structure modifications after prolonged in vitro
      growth or in vivo passaging have been reported previously. However, nothing is
      known about the dynamics of these modifications or about their environmental
      specificities. In this study, capsule structure modifications after mouse
      passaging and prolonged in vitro culturing were analyzed by flow cytometry using
      the glucuronoxylomannan-specific monoclonal antibody E1. The capsule structures
      of strains recovered after 0, 1, 8, and 35 days were compared by using the level
      of E1-specific epitope expression and its cell-to-cell heterogeneity within a
      given cell population. In vitro, according to these parameters, the diversity of
      the strains was higher on day 35 than it was initially, suggesting the absence of
      selection during in vitro culturing. In contrast, the diversity of the strains
      recovered from the brain tended to decrease over time, suggesting that selection
      of more adapted strains had occurred. The strains recovered on day 35 from the
      spleen and the lungs had different phenotypes than the strains isolated from the
      brain of the same mouse on the same day, thus strongly suggesting that there is
      organ specificity for C. neoformans strain selection. Fingerprinting of the
      strains recovered in vitro and in vivo over time confirmed that genotypes evolved
      very differently in vitro and in vivo, depending on the environment. Overall, our
      results suggest that organ-specific selection can occur during cryptococcosis.

PMID- 15155642
TI  - Clostridium sordellii lethal toxin is maintained in a multimeric protein complex.
AB  - Clostridium sordellii lethal toxin (TcsL) is distinct among large clostridial
      toxins (LCTs), as it is markedly reduced in its rate of intoxication at pH 8.0
      yet is cytotoxic at pH 4.0. Results from the present study suggest that TcsL's
      slow rate of intoxication at pH 8.0 is linked to formation of a high-molecular
      weight complex containing dissociable pH 4.0-sensitive polypeptides. The
      cytosolic delivery of TcsL's enzymatic domain by using a surrogate cell entry
      system resulted in cytopathic effect rates similar to those of other LCTs at pH
      8.0, further indicating that rate-limiting steps occurred at the point of cell
      entry. Since these rate-limiting steps could be overcome at pH 4.0, TcsL was
      examined across a range of pH values and was found to dissociate into distinct 45
      to 55-kDa polypeptides between pH 4.0 and pH 5.0. The polypeptides reassociated
      when shifted back to pH 8.0. At pH 8.0, this complex was resistant to sodium
      dodecyl sulfate (SDS) and multiple proteases; however, following dissociation,
      the polypeptides became protease sensitive. Dissociation of TcsL, and
      cytotoxicity, could be blocked by preincubation with ethylene glycol
      bis(sulfosuccinimidylsuccinate), resulting in cross-linking of the polypeptides.
      TcsL was also examined at pH 8.0 by using SDS-agarose gel electrophoresis and
      transmission electron microscopy and was found to exist in a higher-molecular
      weight complex which resolved at a size exceeding 750 kDa and also dissociated at
      pH 4.0. However, this complex did not reassemble following a shift back to pH
      8.0. Collectively, these data suggest that TcsL is maintained in a protease
      resistant, high-molecular-weight complex, which dissociates at pH 4.0, leading to
      cytotoxicity.

PMID- 15155643
TI  - Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst
      NADPH oxidase.
AB  - Reactive oxygen species are a critical weapon in the killing of Aspergillus
      fumigatus by polymorphonuclear leukocytes (PMN), as demonstrated by severe
      aspergillosis in chronic granulomatous disease. In the present study, A.
      fumigatus-produced mycotoxins (fumagillin, gliotoxin [GT], and helvolic acid) are
      examined for their effects on the NADPH oxidase activity in human PMN. Of these
      mycotoxins, only GT significantly and stoichiometrically inhibits phorbol
      myristate acetate (PMA)-stimulated O2- generation, while the other two toxins are
      ineffective. The inhibition is dependent on the disulfide bridge of GT, which
      interferes with oxidase activation but not catalysis of the activated oxidase.
      Specifically, GT inhibits PMA-stimulated events: p47phox phosphorylation, its
      incorporation into the cytoskeleton, and the membrane translocation of p67phox,
      p47phox, and p40phox, which are crucial steps in the assembly of the active NADPH
      oxidase. Thus, damage to p47phox phosphorylation is likely a key to inhibiting
      NADPH oxidase activation. GT does not inhibit the membrane translocation of Rac2.
      The inhibition of p47phox phosphorylation is due to the defective membrane
      translocation of protein kinase C (PKC) betaII rather than an effect of GT on PKC
      betaII activity, suggesting a failure of PKC betaII to associate with the
      substrate, p47phox, on the membrane. These results suggest that A. fumigatus may
      confront PMN by inhibiting the assembly of the NADPH oxidase with its hyphal
      product, GT.

PMID- 15155644
TI  - Mitogenicity of the recombinant mycobacterial 27-kilodalton lipoprotein is not
      connected to its antiprotective effect.
AB  - We reported previously that even though immunization with the recombinant
      mycobacterial 27-kDa lipoprotein (r27) induced a Th1-type response in mice, the
      vaccinated mice became more susceptible to challenge with Mycobacterium
      tuberculosis. In this study we show that r27 stimulates naive splenocytes to
      proliferate. Acylation of r27 was crucial for this effect, since a nonacylated
      mutant of r27, termed r27DeltaSP, failed to stimulate splenocytes either in vitro
      or in vivo. Depletion experiments indicated that only B cells were proliferating
      in a T-cell-independent manner. We also found that r27 is recognized by TLR2,
      which is involved in mitogenic stimulation. Interestingly, r27 but not r27DeltaSP
      induced high gamma interferon levels in splenocyte supernatants, whereas no
      significant interleukin-2 levels were detected. Since B-cell polyclonal
      activation might aggravate pathogen infection, we asked whether the
      antiprotective effect of the r27 lipoprotein is associated with its mitogenicity.
      We showed that, as in the case of r27, immunization of mice with the nonmitogenic
      r27DeltaSP lipoprotein resulted in increased M. tuberculosis multiplication. We
      conclude that the antiprotective effect of the r27 lipoprotein must be linked to
      properties of the polypeptide portion of the lipoprotein rather than to its lipid
      moiety and its mitogenicity.

PMID- 15155645
TI  - Association of type 2 cytokines with hepatic fibrosis in human Schistosoma
      mansoni infection.
AB  - The objective of this study was to evaluate the role of cytokines in hepatic
      fibrosis in the prehepatosplenic and early hepatosplenic stages of
      schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94
      patients. Immunological evaluation was performed by the measurement of secreted
      cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis
      factor alpha, and transforming growth factor beta) in peripheral blood
      mononuclear cells (PBMC) stimulated by Schistosoma mansoni antigens.
      Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants
      of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic
      fibrosis compared to patients with degree I or II fibrosis. Significant increases
      in IL-5 and IL-13 levels were also observed in some of the subjects who remained
      untreated for 1 year following initial assessment and developed more serious
      fibrosis during this period. The data suggest a role for type 2 cytokines in
      hepatic fibrosis in human schistosomiasis mansoni.

PMID- 15155647
TI  - A cardiac myosin-specific autoimmune response is induced by immunization with
      Trypanosoma cruzi proteins.
AB  - Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a
      potentially fatal cardiomyopathy prevalent in Central and South America.
      Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans
      and mice, and this autoimmunity has been suggested to contribute to cardiac
      inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we
      investigated whether immunity to T. cruzi antigens could induce cardiac myosin
      specific autoimmunity in the absence of live parasites. We immunized A/J mice
      with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's
      adjuvant and found that these mice developed cardiac myosin-specific delayed-type
      hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac
      damage. The induction of autoimmunity was specific since immunization with
      extracts of the related protozoan parasite Leishmania amazonensis did not induce
      myosin autoimmunity. The immunogenetic makeup of the host was important for this
      response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization
      with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac
      myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen
      specific, since immunization with skeletal myosin and myoglobin did not induce T.
      cruzi-specific immunity. These results suggest that immunization with cardiac
      myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive
      immune responses in the absence of detectable cardiac damage.

PMID- 15155646
TI  - Characterization of the icmH and icmF genes required for Legionella pneumophila
      intracellular growth, genes that are present in many bacteria associated with
      eukaryotic cells.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, replicates
      intracellularly within a specialized phagosome of mammalian and protozoan host
      cells, and the Icm/Dot type IV secretion system has been shown to be essential
      for this process. Unlike all the other known Icm/Dot proteins, the IcmF protein,
      which was described before, and the IcmH protein, which is characterized here,
      have homologous proteins in many bacteria (such as Yersinia pestis, Salmonella
      enterica, Rhizobium leguminosarum, and Vibrio cholerae), all of which associate
      with eukaryotic cells. Here, we have characterized the L. pneumophila icmH and
      icmF genes and found that both genes are present in 16 different Legionella
      species examined. The icmH and icmF genes were found to be absolutely required
      for intracellular multiplication in Acanthamoeba castellanii and partially
      required for intracellular growth in HL-60-derived human macrophages, for
      immediate cytotoxicity, and for salt sensitivity. Mutagenesis of the predicted
      ATP/GTP binding site of IcmF revealed that the site is partially required for
      intracellular growth in A. castellanii. Analysis of the regulatory region of the
      icmH and icmF genes, which were found to be cotranscribed, revealed that it
      contains at least two regulatory elements. In addition, an icmH::lacZ fusion was
      shown to be activated during stationary phase in a LetA- and RelA-dependent
      manner. Our results indicate that although the icmH and icmF genes probably have
      a different evolutionary origin than the rest of the icm/dot genes, they are part
      of the icm/dot system and are required for L. pneumophila pathogenesis.

PMID- 15155648
TI  - A novel lectin, DltA, is required for expression of a full serum resistance
      phenotype in Haemophilus ducreyi.
AB  - Haemophilus ducreyi, the causative agent of chancroid, is highly resistant to the
      complement-mediated bactericidal activity of normal human serum (NHS).
      Previously, we identified DsrA (for ducreyi serum resistance A), a major factor
      required for expression of the serum resistance phenotype in H. ducreyi. We
      describe here a second outer membrane protein, DltA (for ducreyi lectin A), which
      also contributes to serum resistance in H. ducreyi. Isogenic dltA mutants,
      constructed in 35000HP wild-type and FX517 dsrA backgrounds, were more
      susceptible to the bactericidal effects of NHS than each respective parent,
      demonstrating the additive effect of the mutations. Furthermore, expression of
      dltA in H. influenzae strain Rd rendered this highly susceptible strain partially
      resistant to 5% NHS compared to a vector-control strain. Although primary basic
      local alignment search tool analysis of the dltA open reading frame revealed no
      close bacterial homologue, similarity to the beta-chain of the eukaryotic lectin
      ricin was noted. DltA shares highly conserved structural motifs with the ricin
      beta chain, such as cysteines and lectin-binding domains. To determine whether
      dltA was a lectin, ligand blots and affinity chromatography experiments were
      performed. DltA was affinity purified on immobilized lactose and N
      acetylgalactosamine, and N-glycosylated but not glycosidase-treated model
      glycoproteins bound DltA. These data indicate that DltA is a lectin with
      specificity for lactose-related carbohydrates (CHO) and is important for H.
      ducreyi serum resistance.

PMID- 15155650
TI  - A heptosyltransferase mutant of Pasteurella multocida produces a truncated
      lipopolysaccharide structure and is attenuated in virulence.
AB  - Pasteurella multocida is the causative agent of fowl cholera in birds. In a
      previous study using signature-tagged mutagenesis, we identified a mutant, AL251,
      which was attenuated for virulence in mice and in the natural chicken host.
      Sequence analysis indicated that AL251 had an insertional inactivation of the
      gene waaQ(PM), encoding a putative heptosyl transferase, required for the
      addition of heptose to lipopolysaccharide (LPS) (M. Harper, J. D. Boyce, I. W.
      Wilkie, and B. Adler, Infect. Immun. 71:5440-5446, 2003). In the present study,
      using mass spectrometry and nuclear magnetic resonance, we have confirmed the
      identity of the enzyme encoded by waaQ(PM) as a heptosyl transferase III and
      demonstrated that the predominant LPS glycoforms isolated from this mutant are
      severely truncated. Complementation experiments demonstrated that providing a
      functional waaQ(PM) gene in trans can restore both the LPS to its full length and
      growth in mice to wild-type levels. Furthermore, we have shown that mutant AL251
      is unable to cause fowl cholera in chickens and that the attenuation observed is
      not due to increased serum sensitivity.

PMID- 15155649
TI  - Heterogeneity among Helicobacter pylori strains in expression of the outer
      membrane protein BabA.
AB  - The BabA adhesin of Helicobacter pylori is an outer membrane protein that binds
      to the fucosylated Lewis b histo-blood group antigen on the surface of gastric
      epithelial cells. We screened a phage-displayed ScFv (single-chain fragment
      variable) recombinant antibody library for antibodies reactive with a recombinant
      BabA fragment and identified two such antibodies. Each antibody recognized an
      approximately 75-kDa protein present in wild-type H. pylori strain J99 but absent
      from an isogenic babA mutant strain. An immunoreactive BabA protein was detected
      by at least one of the antibodies in 18 (46%) of 39 different wild-type H. pylori
      strains and was detected more commonly in cagA-positive strains than in cagA
      negative strains. Numerous amino acid polymorphisms were detected among BabA
      proteins expressed by different strains, with the greatest diversity occurring in
      the middle region of the proteins. Among the 18 strains that expressed a
      detectable BabA protein, there was considerable variation in the level of binding
      to Lewis b in vitro. Heterogeneity among H. pylori strains in expression of the
      BabA protein may be a factor that contributes to differing clinical outcomes
      among H. pylori-infected humans.

PMID- 15155651
TI  - Mucosal vaccine made from live, recombinant Lactococcus lactis protects mice
      against pharyngeal infection with Streptococcus pyogenes.
AB  - A novel vaccine (LL-CRR) made from live, nonpathogenic Lactococcus lactis that
      expresses the conserved C-repeat region (CRR) of M protein from Streptococcus
      pyogenes serotype 6 was tested in mice. Nasally vaccinated mice produced CRR
      specific salivary immunoglobulin A (IgA) and serum IgG. Subcutaneously vaccinated
      mice produced CRR-specific serum IgG but not salivary IgA. A combined regimen
      produced responses similar to the salivary IgA of nasally vaccinated mice and
      serum IgG of subcutaneously vaccinated mice. Mice vaccinated nasally or with the
      combined regimen were significantly protected against pharyngeal infection
      following a nasal challenge with S. pyogenes M serotype 14. Mice vaccinated
      subcutaneously were not protected against pharyngeal infection. Mice in all three
      LL-CRR vaccination groups were significantly protected against the lethal effects
      of S. pyogenes. Only 1 of 77 challenged mice that were vaccinated with LL-CRR
      died, whereas 60 of 118 challenged mice that were vaccinated with a control
      strain or phosphate-buffered saline died. In conclusion, mucosal vaccination with
      LL-CRR produced CRR-specific salivary IgA and serum IgG, prevented pharyngeal
      infection with S. pyogenes, and promoted survival.

PMID- 15155653
TI  - Role of transferrin receptor from a Neisseria meningitidis tbpB isotype II strain
      in human transferrin binding and virulence.
AB  - Neisseria meningitidis acquires iron through the action of the transferrin (Tf)
      receptor, which is composed of the Tf-binding proteins A and B (TbpA and TbpB).
      Meningococci can be classified into isotype I and II strains depending on whether
      they harbor a type I or II form of TbpB. Both types of TbpB have been shown to
      differ in their genomic, biochemical, and antigenic properties. Here we present a
      comparative study of isogenic mutants deficient in either or both Tbps from the
      isotype I strain B16B6 and isotype II strain M982. We show that TbpA is essential
      in both strains for iron uptake and growth with iron-loaded human Tf as a sole
      iron source. No growth has also been observed for the TbpB- mutant of strain
      B16B6, as shown previously, whereas the growth of the analogous mutant in M982
      was similar to that in the wild type. This indicates that TbpB in the latter
      strain plays a facilitating but not essential role in iron uptake, which has been
      observed previously in similar studies of other bacteria. These data are
      discussed in relation to the fact that isotype II strains represent more than 80%
      of serogroup B meningococcal strains. The contribution of both subunits in the
      bacterial virulence of strain M982 has been assessed in a murine model of
      bacteremia. Both the TbpB- TbpA- mutant and the TbpA- mutant are shown to be
      nonvirulent in mice, whereas the virulence of the TbpB- mutant is similar to that
      of the wild type.

PMID- 15155652
TI  - Surface plasmon resonance analysis of antipolysaccharide antibody specificity:
      responses to meningococcal group C conjugate vaccines and bacteria.
AB  - Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis
      group C PS (MCPS), are characterized as being thymus independent and are
      restricted with regard to clonotype and isotype expression. PS conjugated to
      proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin
      derivative CRM197, elicit thymus-dependent responses. The present study developed
      a surface plasmon resonance approach to evaluate Ab responses to MCPS conjugate
      vaccines, including either O-acetylated (OAc+) or de-O-acetylated (OAc-) forms of
      the PS. The results were generally consistent with those obtained by enzyme
      linked immunosorbent assay and showed that sera from mice immunized with
      conjugate vaccines contain Abs that bind more effectively to OAc+ and OAc- MCPS
      than sera from mice immunized with fixed bacteria. The data suggest a critical
      shared or overlapping epitope recognized by all the conjugate vaccine immune sera
      and strategies for assessing polyclonal Ab avidity.

PMID- 15155654
TI  - Contribution of immunological memory to protective immunity conferred by a
      Bacillus anthracis protective antigen-based vaccine.
AB  - Protective antigen (PA)-based vaccination is an effective countermeasure to
      anthrax infection. While neutralizing anti-PA antibody titers elicited by this
      vaccine serve as good correlates for protection against anthrax (S. Reuveny, M.
      D. White, Y. Y. Adar, Y. Kafri, Z. Altboum, Y. Gozes, D. Kobiler, A. Shafferman,
      and B. Velan, Infect. Immun. 69:2888-2893, 2001), no data are available on the
      contribution of the immunological memory for PA itself to protection. We
      therefore developed a guinea pig model in which a primary immunization with
      threshold levels of PA can induce a long-term T-cell immunological memory
      response without inducing detectable anti-PA antibodies. A revaccination of
      primed animals with the same threshold PA levels was effective for memory
      activation, yielding a robust and rapid secondary response. A challenge with a
      lethal dose (40 50% lethal doses; 2,000 spores) of spores after the booster
      vaccinations indicated that animals were not protected at days 2, 4, and 6
      postboosting. Protection was achieved only from the 8th day postboosting,
      concomitant with the detection of protective levels of neutralizing antibody
      titers in the circulation. The practical implications from the studies reported
      herein are that, as expected, the protective capacity of memory depends on the PA
      dose used for the primary immunization and that the effectiveness of booster
      immunizations for the postexposure treatment of anthrax may be very limited when
      no detectable antibodies are present in primed animals prior to Bacillus
      anthracis spore exposure. Therefore, to allow for the establishment of memory
      dependent protection prior to the expected onset of disease, booster
      immunizations should not be used without concomitant antimicrobial treatment in
      postexposure scenarios.

PMID- 15155655
TI  - Interaction of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma
      capsulatum with Acanthamoeba castellanii.
AB  - Several dimorphic fungi are important human pathogens, but the origin and
      maintenance of virulence in these organisms is enigmatic, since an interaction
      with a mammalian host is not a requisite for fungal survival. Recently,
      Cryptococcus neoformans was shown to interact with macrophages, slime molds, and
      amoebae in a similar manner, suggesting that fungal pathogenic strategies may
      arise from environmental interactions with phagocytic microorganisms. In this
      study, we examined the interactions of three dimorphic fungi with the soil amoeba
      Acanthameobae castellanii. Yeast forms of Blastomyces dermatitidis, Sporothrix
      schenckii, and Histoplasma capsulatum were each ingested by amoebae and
      macrophages, and phagocytosis of yeast cells resulted in amoeba death and fungal
      growth. H. capsulatum conidia were also cytotoxic to amoebae. For each fungal
      species, exposure of yeast cells to amoebae resulted in an increase in hyphal
      cells. Exposure of an avirulent laboratory strain of H. capsulatum to A.
      castellanii selected for, or induced, a phenotype of H. capsulatum that caused a
      persistent murine lung infection. These results are consistent with the view that
      soil amoebae may contribute to the selection and maintenance of certain traits in
      pathogenic dimorphic fungi that confer on these microbes the capacity for
      virulence in mammals.

PMID- 15155656
TI  - Identification of a novel two-component system in Streptococcus gordonii V288
      involved in biofilm formation.
AB  - Streptococcus gordonii is a pioneer colonizer of the teeth, contributing to the
      initiation of the oral biofilm called dental plaque. To identify genes that may
      be important in biofilm formation, a plasmid integration library of S. gordonii
      V288 was used. After screening for in vitro biofilm formation on polystyrene, a
      putative biofilm-defective mutant was isolated. In this mutant, pAK36 was
      inserted into a locus encoding a novel two-component system (bfr [biofilm
      formation related]) with two cotranscribed genes that form an operon. bfrA
      encodes a putative response regulator, while bfrB encodes a receptor histidine
      kinase. The bfr mutant and wild-type strain V288 showed similar growth rates in
      Todd-Hewitt broth (THB). A bfr-cat fusion strain was constructed. During growth
      in THB, the reporter activity (chloramphenicol acetyltransferase) was first
      detected in mid-log phase and reached a maximum in stationary phase, suggesting
      that transcription of bfr was growth stage dependent. After being harvested from
      THB, the bfr mutant adhered less effectively than did wild-type strain V288 to
      saliva-coated hydroxyapatite (sHA). To simulate pioneer colonization of teeth, S.
      gordonii V288 was incubated with sHA for 4 h in THB with 10% saliva to develop
      biofilms. RNA was isolated, and expression of bfrAB was estimated. In comparison
      to that of cells grown in suspension (free-growing cells), bfr mRNA expression by
      sessile cells on sHA was 1.8-fold greater and that by surrounding planktonic
      cells was 3.5-fold greater. Therefore, bfrAB is a novel two-component system
      regulated in association with S. gordonii biofilm formation in vitro.

PMID- 15155657
TI  - The novel fibrinogen-binding protein FbsB promotes Streptococcus agalactiae
      invasion into epithelial cells.
AB  - Streptococcus agalactiae is a major cause of bacterial sepsis and meningitis in
      human newborns. The interaction of S. agalactiae with host proteins and the entry
      into host cells thereby represent important virulence traits of these bacteria.
      The present report describes the identification of the fbsB gene, encoding a
      novel fibrinogen-binding protein that plays a crucial role in the invasion of S.
      agalactiae into human cells. In Western blots and enzyme-linked immunosorbent
      assay (ELISA) experiments, the FbsB protein was demonstrated to interact with
      soluble and immobilized fibrinogen. Binding studies showed the N-terminal 388
      residues of FbsB and the Aalpha-subunit of human fibrinogen to recognize each
      other. By reverse transcription (RT)-PCR, the fbsB gene was shown to be
      cotranscribed with the gbs0851 gene in S. agalactiae. Deletion of the fbsB gene
      in the genome of S. agalactiae did not influence the binding of the bacteria to
      fibrinogen, suggesting that FbsB does not participate in the attachment of S.
      agalactiae to fibrinogen. In tissue culture experiments, however, the fbsB
      deletion mutant was severely impaired in its invasion into lung epithelial cells.
      Bacterial invasion could be reestablished by introducing the fbsB gene on a
      shuttle plasmid into the fbsB deletion mutant. Furthermore, treatment of lung
      epithelial cells with FbsB fusion protein blocked S. agalactiae invasion of
      epithelial cells in a dose-dependent fashion. These results suggest an important
      role of the FbsB protein in the overall process of host cell entry by S.
      agalactiae.

PMID- 15155658
TI  - Somatic hypermutation and diverse immunoglobulin gene usage in the human antibody
      response to the capsular polysaccharide of Streptococcus pneumoniae Type 6B.
AB  - Combinatorial cloning and expression library analysis were used to determine the
      expressed human antibody repertoire specific for the capsular polysaccharide (PS)
      of Streptococcus pneumoniae serotype 6B. Sequence analysis of 55 6B-specific
      antibody Fab fragments isolated from six vaccinated donors reveal that different
      individuals used a variety of heavy and light chain germ line variable (V) region
      genes to form pneumococcal capsular PS (PPS) 6B-specific paratopes. Within each
      donor, however, the response was more restricted, with five of the six donors
      using at most one or two gene pairs to form combining sites. Analysis also
      indicated that although the response in each donor was oligoclonal in terms of
      variable gene usage, the combination of extensive somatic hypermutation, deletion
      of germ line-encoded residues, insertion of non-germ line-encoded residues, and
      intraclonal isotype switching generated a surprising degree of paratope diversity
      within the individuals analyzed. In contrast to previously studied PS-specific
      responses, we find that the PPS 6B repertoire makes use of a diverse collection
      of heavy-chain and light-chain V region gene products to form specific paratopes,
      with no apparent tendency for conservation of immunoglobulin gene usage between
      individuals.

PMID- 15155659
TI  - Specific in vivo deletion of B-cell subpopulations expressing human
      immunoglobulins by the B-cell superantigen protein L.
AB  - Some pathogens have evolved to produce proteins, called B-cell superantigens,
      that can interact with human immunoglobulin variable regions, independently of
      the combining site, and activate B lymphocytes that express the target
      immunoglobulins. However, the in vivo consequences of these interactions on human
      B-cell numbers and function are largely unknown. Using transgenic mice expressing
      fully human immunoglobulins, we studied the consequences of in vivo exposure of
      protein L of Peptostreptococcus magnus with human immunoglobulins. In the mature
      pool of B cells, protein L exposure resulted in a specific reduction of splenic
      marginal-zone B cells and peritoneal B-1 cells. Splenic B cells exhibited a
      skewed light-chain repertoire consistent with the capacity of protein L to bind
      specific kappa gene products. Remarkably, these two B-cell subsets are implicated
      in innate B-cell immunity, allowing rapid clearance of pathogens. Thus, the
      present study reveals a novel mechanism that may be used by some infectious
      agents to subvert a first line of the host's immune defense.

PMID- 15155660
TI  - Effect of antibody on the rickettsia-host cell interaction.
AB  - A recent study demonstrated that polyclonal antibodies to Rickettsia conorii and
      monoclonal antibodies to outer membrane proteins A (OmpA) and B (OmpB) provided
      effective, Fc-dependent, passive immunity, even in severe combined
      immunodeficient mice with an established infection. In order to determine the
      mechanism of protection, mouse endothelial and macrophage-like cell lines were
      infected with R. conorii that had been exposed to polyclonal antibodies,
      monoclonal antibodies to OmpA or OmpB, Fab fragments of the polyclonal
      antibodies, or normal serum or that were left untreated. At 0 h, Fc-dependent
      antibody enhancement of R. conorii adherence to endothelial and macrophage-like
      cell lines was inhibited by the presence of normal serum, suggesting Fc receptor
      mediated adherence of opsonized rickettsiae. At 3 h, the opsonized rickettsiae
      had been internalized. After 72 h, inhibited survival of rickettsiae exposed to
      polyclonal antibodies or monoclonal antibodies to OmpA or OmpB was evident
      compared with growth of untreated and normal serum-treated and polyclonal Fab
      antibody-treated R. conorii. Polyclonal antibodies and an anti-OmpB monoclonal
      antibody inhibited the escape of R. conorii from the phagosome, resulting in
      intraphagolysosomal rickettsial death. At 48 h of infection, rickettsicidal
      activity of macrophages by opsonized rickettsiae was inhibited by NG-monomethyl-L
      arginine, superoxide dismutase, mannitol, or supplemental L-tryptophan, and
      endothelial rickettsicidal activity against opsonized rickettsiae was inhibited
      by NG-monomethyl-L-arginine, superoxide dismutase, catalase, or supplemental L
      tryptophan. Thus, Fc-dependent antibodies protected against R. conorii infection
      of endothelium and macrophages by opsonization that inhibited phagosomal escape
      and resulted in phagolysosomal killing mediated by nitric oxide, reactive oxygen
      intermediates, and L-tryptophan starvation.

PMID- 15155661
TI  - Geographical and temporal conservation of antibody recognition of Plasmodium
      falciparum variant surface antigens.
AB  - The slow acquisition of protection against Plasmodium falciparum malaria probably
      reflects the extensive diversity of important antigens. The variant surface
      antigens (VSA) that mediate parasite adhesion to a range of host molecules are
      regarded as important targets of acquired protective immunity, but their
      diversity makes them questionable vaccine candidates. We determined levels of VSA
      specific immunoglobulin G (IgG) in human plasma collected at four geographically
      distant and epidemiologically distinct localities with specificity for VSA
      expressed by P. falciparum isolates from three African countries. Plasma levels
      of VSA-specific IgG recognizing individual parasite isolates depended on the
      transmission intensity at the site of plasma collection but were largely
      independent of the geographical origin of the parasites. The total repertoire of
      immunologically distinct VSA thus appears to be finite and geographically
      conserved, most likely due to functional constraints. Furthermore, plasma samples
      frequently had high IgG reactivity to VSA expressed by parasites isolated more
      than 10 years later, showing that the repertoire is also temporally stable.
      Parasites from patients with severe malaria expressed VSA (VSASM) that were
      better recognized by plasma IgG than VSA expressed by other parasites, but
      importantly, VSASM-type antigens also appeared to show substantial antigenic
      homogeneity. Our finding that the repertoire of immunologically distinct VSA in
      general, and in particular that of VSASM, is geographically and temporally
      conserved raises hopes for the feasibility of developing VSA-based vaccines
      specifically designed to accelerate naturally acquired immunity, thereby
      enhancing protection against severe and life-threatening P. falciparum malaria.

PMID- 15155662
TI  - Role of CD8+ and CD4+ T lymphocytes in jejunal mucosal injury during murine
      giardiasis.
AB  - T-cell-mediated pathogenesis has been documented in various idiopathic and
      microbially induced intestinal disorders. Diffuse microvillous shortening seen in
      giardiasis is responsible for disaccharidase insufficiencies and malabsorption of
      electrolytes, nutrients, and water. Other mucosal changes include crypt
      hyperplasia and increased numbers of intraepithelial lymphocytes (IEL). A recent
      report using an athymic mouse model of infection showed that these epithelial
      injuries were dependent on T cells. The aim of the present study was to identify
      which subset of superior mesenteric lymph node (SMLN) T cells were responsible
      for mucosal alterations in giardiasis. CD4+ and CD8+ T cells, as well as whole
      lymphocyte populations, were isolated from SMLN of Giardia muris-infected mice
      for adoptive transfer. Jejunal segments of recipient mice were assessed for brush
      border ultrastructure, sucrase activity, crypt/villus ratio, and IEL numbers.
      Mice that received enriched CD8+ and whole SMLN lymphocytes, but not CD4+ T
      cells, from infected donors showed diffuse shortening of microvilli, loss of
      brush border surface area, impaired sucrase activity, and increased crypt/villus
      ratios compared to respective controls. Transfer of whole SMLN lymphocytes, as
      well as enriched CD4+ or CD8+ T cells, from infected donors led to increased IEL
      numbers in the recipient jejunum. The findings indicate that loss of intestinal
      brush border surface area, reduced disaccharidase activities, and increased
      crypt/villus ratios in giardiasis are mediated by CD8+ T cells, whereas both CD8+
      and CD4+ SMLN T cells regulate the influx of IEL.

PMID- 15155663
TI  - CpG oligodeoxynucleotides improve the survival of pregnant and fetal mice
      following Listeria monocytogenes infection.
AB  - Listeria infection during pregnancy can cause the death of both mother and fetus.
      Previous studies established that immunostimulatory CpG oligodeoxynucleotides
      (ODN) increase the resistance of healthy adult mice to many infectious pathogens,
      including Listeria monocytogenes. This study examines whether the innate immune
      response elicited by CpG ODN can reduce the susceptibility of pregnant mice to
      lethal listeria challenge. The results indicate that CpG ODN treatment
      significantly improves maternal survival and reduces pathogen transmission to
      offspring. CpG ODN administered during pregnancy did not induce abortion, birth
      defects, or reduce the size or health of litters. These findings suggest that CpG
      ODN may provide a safe and effective means of improving the health of mothers and
      fetuses during pregnancy.

PMID- 15155664
TI  - Helicobacter pylori activates the early growth response 1 protein in gastric
      epithelial cells.
AB  - The early growth response 1 (Egr-1) transcription factor is rapidly induced by
      various stimuli and is implicated in the regulation of cell growth,
      differentiation, and gene expression. The aim of this study was to examine the
      effect of Helicobacter pylori on the expression of Egr-1 and Egr-1-regulated
      genes in gastric epithelial AGS cells. Egr-1 expression was assayed by
      immunoblotting and electrophoretic mobility shift assays using H. pylori
      stimulated AGS cells. Transient transfection experiments with promoter-reporter
      constructs of CD44, ICAM-1, and CD95L were used for expression studies. H. pylori
      induced the expression of Egr-1 in gastric epithelial cell lines in a dose
      dependent manner, with the rapid kinetics that are typical of this class of
      transcription factors. Immunohistochemical studies of biopsies revealed that Egr
      1 expression is more abundant in H. pylori-positive patients than in uninfected
      individuals. Reporter-promoter transfection studies indicated that Egr-1 binding
      is required for the H. pylori-induced transcriptional promoter activity of the
      CD44, ICAM-1, and CD95L (APO-1/Fas) constructs. The blocking of egr-1 with an
      antisense sequence prevented H. pylori-induced Egr-1 and CD44 protein expression.
      The MEK1/2 signaling cascade participates in H. pylori-mediated Egr-1 expression,
      but the p38 pathway does not. The data indicate that H. pylori induces Egr-1
      expression in AGS cells in vitro and that the Egr-1 protein is readily detectable
      in biopsies from H. pylori-positive subjects. These observations suggest that H.
      pylori-associated Egr-1 expression may play a role, in part, in H. pylori-induced
      pathology.

PMID- 15155665
TI  - Protective role of interleukin-6 during Yersinia enterocolitica infection is
      mediated through the modulation of inflammatory cytokines.
AB  - Yersinia enterocolitica is a gram-negative enteric pathogen responsible for a
      number of gastrointestinal disorders. A striking feature of the pathology of a Y.
      enterocolitica infection is inflammation. Recently, we demonstrated a role for
      interleukin-1alpha (IL-1alpha) in the establishment of intestinal inflammation in
      response to a Y. enterocolitica infection. A cytokine directly affected by IL-1
      levels is IL-6. A previous report suggested that IL-6 plays an anti-inflammatory
      role during Y. enterocolitica infection, and in other systems IL-6 has been shown
      to be proinflammatory. Therefore, a closer examination of the roles of IL-6 and
      inflammatory cytokines in the control of Y. enterocolitica infection in IL-6(-/-)
      mice was undertaken. Y. enterocolitica organisms were more virulent in the IL-6(
      /-) mice (60-fold decreased 50% lethal dose) and colonized systemic tissues more
      rapidly and to a higher level than in the wild-type mice. One role of IL-6 during
      a Y. enterocolitica infection may be the downmodulation of the inflammatory
      response. The IL-6(-/-) mice have a more robust T(H)1 T-cell response, as well as
      hyperinflammatory pathologies. These phenotypes appear to be due to the
      misregulation of tumor necrosis factor alpha, monocyte chemotactic protein 1, IL
      10, transforming growth factor beta1, and gamma interferon in the IL-6(-/-)
      mouse. These data provide further insight into the intricate cytokine signaling
      pathways involved in the regulation of inflammatory responses and the control of
      bacterial infections.

PMID- 15155666
TI  - Infection with Toxoplasma gondii increases atherosclerotic lesion in ApoE
      deficient mice.
AB  - Toxoplasma gondii is an intracellular protozoan that elicits a potent
      inflammatory response during the acute phase of infection. Herein, we evaluate
      whether T. gondii infection alters the natural course of aortic lesions. ApoE
      knockout mice were infected with T. gondii, and at 5 weeks of infection, serum,
      feces, and liver cholesterol; aortic lesion size, cellularity, and inflammatory
      cytokines; and levels of serum nitrite and gamma interferon (IFN-gamma) were
      analyzed. Our results showed that serum cholesterol and atherogenic lipoproteins
      were reduced after T. gondii infection. The reduction of serum levels of total
      cholesterol and atherogenic lipoproteins was associated with increases in the
      aortic lesion area, numbers of inflammatory cells, and expression of monocyte
      chemoattractant protein 1 and inducible nitric oxide synthase mRNA in the site of
      lesions as well as elevated concentrations of IFN-gamma and nitrite in sera of T.
      gondii-infected animals. These results suggest that infection with T. gondii
      accelerates atherosclerotic development by stimulating the proinflammatory
      response and oxidative stress, thereby increasing the area of aortic lesion.

PMID- 15155667
TI  - The Vibrio cholerae ToxR-regulated porin OmpU confers resistance to antimicrobial
      peptides.
AB  - BPI (bactericidal/permeability-increasing) is a potent antimicrobial protein that
      was recently reported to be expressed as a surface protein on human
      gastrointestinal tract epithelial cells. In this study, we investigated the
      resistance of Vibrio cholerae, a small-bowel pathogen that causes cholera, to a
      BPI-derived peptide, P2. Unlike in Escherichia coli and Salmonella enterica
      serovar Typhimurium, resistance to P2 in V. cholerae was not dependent on the
      BipA GTPase. Instead, we found that ToxR, the master regulator of V. cholerae
      pathogenicity, controlled resistance to P2 by regulating the production of the
      outer membrane protein OmpU. Both toxR and ompU mutants were at least 100-fold
      more sensitive to P2 than were wild-type cells. OmpU also conferred resistance to
      polymyxin B sulfate, suggesting that this porin may impart resistance to cationic
      antibacterial proteins via a common mechanism. Studies of stationary-phase cells
      revealed that the ToxR-repressed porin OmpT may also contribute to P2 resistance.
      Finally, although the mechanism of porin-mediated resistance to antimicrobial
      peptides remains elusive, our data suggest that the BPI peptide sensitivity of
      OmpU-deficient V. cholerae is not attributable to a generally defective outer
      membrane.

PMID- 15155668
TI  - Role of HtrA in the virulence and competence of Streptococcus pneumoniae.
AB  - HtrA is a major virulence factor of Streptococcus pneumoniae (the pneumococcus).
      Deletion of the gene for HtrA from strain D39 of the pneumococcus completely
      abolished its virulence in mouse models of pneumonia and bacteremia, while the
      virulence of a second strain (TIGR4) was dramatically reduced. HtrA-negative
      mutants induced much less inflammation in the lungs during pneumonia than the
      wild type. HtrA is involved in the ability of the pneumococcus to grow at high
      temperatures, to resist oxidative stress, and to undergo genetic transformation.
      The expression and cellular location of several known virulence factors of the
      pneumococcus were not affected by the lack of HtrA.

PMID- 15155669
TI  - Legionella dumoffii DjlA, a member of the DnaJ family, is required for
      intracellular growth.
AB  - Legionella dumoffii is one of the common causes of Legionnaires' disease and is
      capable of replicating in macrophages. To understand the mechanism of survival
      within macrophages, transposon mutagenesis was employed to isolate the genes
      necessary for intracellular growth. We identified four defective mutants after
      screening 790 transposon insertion mutants. Two transposon insertions were in
      genes homologous to icmB or dotC, within dot/icm loci, required for intracellular
      multiplication of L. pneumophila. The third was in a gene whose product is
      homologous to the 17-kDa antigen forming part of the VirB/VirD4 type IV secretion
      system of Bartonella henselae. The fourth was in the djlA (for "dnaj-like A")
      gene. DjlA is a member of the DnaJ/Hsp40 family. Transcomplementation of the djlA
      mutant restored the parental phenotype in J774 macrophages, A549 human alveolar
      epithelial cells, and the amoeba Acanthamoeba culbertsoni. Using confocal laser
      scanning microscopy and transmission electron microscopy, we revealed that in
      contrast to the wild-type strain, L. dumoffii djlA mutant-containing phagosomes
      were unable to inhibit phagosome-lysosome fusion. Transmission electron
      microscopy also showed that in contrast to the virulent parental strain, the djlA
      mutant was not able to recruit host cell rough endoplasmic reticulum.
      Furthermore, the stationary-phase L. dumoffii djlA mutants were more susceptible
      to H2O2, high osmolarity, high temperature, and low pH than was their parental
      strain. These results indicate that DjlA is required for intracellular growth and
      organelle trafficking, as well as bacterial resistance to environmental stress.
      This is the first report demonstrating that a single DjlA-deficient mutant
      exhibits a distinct phenotype.

PMID- 15155670
TI  - Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development
      in vitro.
AB  - MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion
      of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical
      organelle protein is structurally similar to the ebl erythrocyte binding
      proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are
      similar to part of the extracellular domain of apical membrane antigen 1 and not
      the Duffy binding-like domain. Although midgut and salivary gland sporozoites are
      morphologically similar, salivary gland sporozoites undergo a period of new gene
      expression after infecting the salivary glands, display distinct phenotypic
      differences, and are more infectious for the mammalian host. The objectives of
      this project were to determine the molecular form of MAEBL in the infectious
      salivary gland sporozoites and whether the ligand has a role in the sporozoite
      development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is
      newly expressed in salivary gland sporozoites and in a form distinct from what is
      present in the midgut sporozoites or present in erythrocytic stages. Both ligand
      domains (M1 and M2) were expressed as part of a full-length membrane form of
      MAEBL in the salivary gland sporozoites in contrast to the other stages that
      retain only the M2 ligand domain as part of the membrane form of the protein.
      Antisera developed against the cysteine-rich regions of the extracellular portion
      of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro.
      Together these data indicate that MAEBL has a role in this third developmental
      stage in the life cycle of the malaria parasite. Thus, MAEBL is another target
      for pre-erythrocytic-stage vaccine development against malaria parasites.

PMID- 15155671
TI  - The serine protease motif of EspC from enteropathogenic Escherichia coli produces
      epithelial damage by a mechanism different from that of Pet toxin from
      enteroaggregative E. coli.
AB  - EspC (Escherichia coli secreted protein C) of enteropathogenic E. coli (EPEC)
      shows the three classical domains of the autotransporter proteins and has a
      conserved serine protease motif belonging to the SPATE (serine protease
      autotransporters of Enterobacteriaceae) subfamily. EspC and its homolog Pet in
      enteroaggregative E. coli (EAEC) bear the same sequence within the serine
      protease motif, and both proteins produce enterotoxic effects, suggesting that
      like Pet, EspC could be internalized to reach and cleave the calmodulin-binding
      domain of fodrin, causing actin cytoskeleton disruption. Even though both
      proteins cause cytoskeleton damage by virtue of their serine protease motifs, the
      following evidence supports the hypothesis that the mechanisms are different. (i)
      To obtain similar cytotoxic and cytoskeletal effects, a threefold-higher EspC
      concentration and a twofold-higher exposure time are needed. (ii) EspC
      internalization into epithelial cells takes more time (6 h) than Pet
      internalization (30 min), and the distributions of the two proteins inside the
      cells are also different. (iii) Both proteins have affinity for fodrin and cleave
      it, but the cleavage sites are different; EspC produces two cleavages, while Pet
      produces just one. (iv) EspC does not cause fodrin redistribution within
      epithelial cells. (v) An EspC serine protease motif mutant, but not a Pet serine
      protease mutant, competes with EspC by blocking cytoskeletal damage. All these
      data suggest that the protein conformational structure is very important for the
      activity of the catalytic site, influencing its interaction with the target
      protein and its internalization. The differences between these proteins may
      explain the reduced ability of EspC to cause cytopathic effects. However, these
      differences may confer a specialized role on EspC in the pathogenesis of EPEC,
      which is different from that of Pet in EAEC pathogenesis.

PMID- 15155672
TI  - Identification of a compensatory mutant (lpg2-REV) of Leishmania major able to
      survive as amastigotes within macrophages without LPG2-dependent glycoconjugates
      and its significance to virulence and immunization strategies.
AB  - Different Leishmania species rely to different extents on abundant
      glycoconjugates, such as lipophosphoglycan (LPG) and related molecules, in
      mammalian infections. Previously, we showed that Leishmania major deletion
      mutants lacking the Golgi GDP-mannose transporter LPG2, which is required for
      assembly of the dominant phosphoglycan (PG) repeats of LPG, were unable to
      survive in macrophages. These lpg2- mutants, however, retained the ability to
      generate asymptomatic, persistent infections in mice. In contrast, Ilg and
      colleagues showed that Leishmania mexicana LPG2 mutants retained virulence for
      mice. Here we identified a partial revertant population of the L. major lpg2-
      mutants (designated lpg2(-)REV) that had regained the ability to replicate in
      macrophages and induce disease pathology through a compensatory change. Like the
      lpg2 parent, the lpg2(-)REV revertant was unable to synthesize LPG2-dependent PGs
      in the promastigote stage and thus remained highly attenuated in the ability to
      induce infection. However, after considerable delay lpg2(-)REV revertant-infected
      mice exhibited lesions, and amastigotes isolated from these lesions were able to
      replicate within macrophages despite the fact that they were unable to synthesize
      PGs. Thus, in some respects, the lpg2(-)REV amastigotes resemble L. mexicana
      amastigotes. Future studies of the gene(s) responsible may shed light on the
      mechanisms employed by L. major to survive in the absence of LPG2-dependent
      glycoconjugates and may also improve the potential of the lpg2- L. major line to
      serve as a live parasite vaccine by overcoming its tendency to revert toward
      virulence.

PMID- 15155674
TI  - Increased susceptibility of beta7-integrin-deficient neonatal mice in the early
      stage of Cryptosporidium parvum infection.
AB  - Numerous inflammatory cells are recruited in response to Cryptosporidium parvum
      infection. These cells include interferon gamma-producing T lymphocytes, which
      are of major importance for the resolution of infection. Here, we show that beta7
      integrin is not essential for the control of infection in mice but that beta7
      deficient neonatal mice are more susceptible during the early stages of
      infection.

PMID- 15155673
TI  - Contribution of gelatinase, serine protease, and fsr to the pathogenesis of
      Enterococcus faecalis endophthalmitis.
AB  - Gelatinase and serine protease were found to contribute in concert to
      pathogenesis in a rabbit model of endophthalmitis. However, a mutant defective in
      the fsr regulator was observed to be more attenuated than a mutant rendered
      defective in the expression of gelatinase and serine protease as the result of a
      polar transposon insertion into the former. This increased attenuation suggests
      that there are possible additional pleiotropic effects of the defect in fsr on
      expression of traits contributing to the pathogenesis of enterococcal infection.

PMID- 15155675
TI  - Delivery of the immunosuppressive antigen Salp15 to antigen-presenting cells by
      Salmonella enterica serovar Typhimurium aroA mutants.
AB  - A Salmonella enterica serovar Typhimurium aroA-deficient delivery system was used
      to target the immunosuppressive protein Salp15 to antigen-presenting cells. In
      vitro and in vivo infections with Salp15-containing Salmonella resulted in an
      impaired CD4(+)-T-cell activation, suggesting that the protein was produced by
      antigen-presenting cells in a physiologically active form.

PMID- 15155676
TI  - The alpha-specific cell identity factor Sxi1alpha is not required for virulence
      of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a human fungal pathogen that has two mating types (a
      and alpha). Experiments have shown that in some backgrounds alpha strains are
      more virulent than a strains. Our studies reveal that the only known alpha
      specific factor, SXI1alpha, is not necessary for virulence.

PMID- 15155677
TI  - Helicobacter pylori induces AGS cell motility and elongation via independent
      signaling pathways.
AB  - Helicobacter pylori induces motogenic and cytoskeletal responses in gastric
      epithelial cells. We demonstrate that these responses can be induced via
      independent signaling pathways that often occur in parallel. The cag
      pathogenicity island appears to be nonessential for induction of motility,
      whereas the elongation phenotype depends on translocation and phosphorylation of
      CagA.

PMID- 15155678
TI  - Induction of de novo subcortical actin filament assembly by Treponema denticola
      major outer sheath protein.
AB  - Treponema denticola and its major outer sheath protein (Msp) induce actin
      reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to
      monitor Msp-induced subcortical actin filament assembly in neutrophils and
      fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of
      these dissimilar cell types, whose cytoskeletal functions in locomotion and
      phagocytosis are crucial for immunity and healing of peripheral infections.

PMID- 15155679
TI  - Porphyromonas gingivalis RgpA and Kgp proteinases and adhesins are C terminally
      processed by the carboxypeptidase CPG70.
AB  - Porphyromonas gingivalis is a bacterial pathogen that produces the polyproteins
      RgpA and Kgp, which are proteolytically processed into proteinases and adhesins.
      We have demonstrated that the RgpA and Kgp proteinases and adhesins are C
      terminally processed by carboxypeptidase CPG70 by sequencing C-terminal peptides
      from both the wild type and an isogenic CPG70 mutant, using ion trap mass
      spectrometry.

PMID- 15155681
TI  - Biological properties of staphylococcal enterotoxin-like toxin type R.
AB  - We investigated the biological properties of a novel staphylococcal enterotoxin
      like putative toxin, staphylococcal enterotoxin-like toxin type R (SElR). Major
      histocompatibility complex class II molecules were required for T-cell
      stimulation by SElR. SElR stimulated T cells bearing receptors Vbeta 3, 11, 12,
      13.2, and 14. These results suggested that SElR acts as a superantigen.

PMID- 15155680
TI  - Influence of origin of isolates, especially endocarditis isolates, and various
      genes on biofilm formation by Enterococcus faecalis.
AB  - Endocarditis isolates of Enterococcus faecalis produced biofilm significantly
      more often than nonendocarditis isolates, and 39% of 79 versus 6% of 84 isolates
      produced strong biofilm (P < 0.0001). esp was not required, but its presence was
      associated with higher amounts of biofilm (P < 0.001). Mutants disrupted in dltA,
      efaA, ace, lsa, and six two-component regulatory systems were largely unaltered,
      while disruptions in epa (encoding enterococcal polysaccharide antigen), atn
      (encoding an autolysin), gelE (encoding gelatinase), and fsr (encoding the E.
      faecalis regulator) [corrected] resulted in fewer attached bacteria, as
      determined using phase-contrast microscopy, and less biofilm (P < 0.0001).

PMID- 15155682
TI  - Role of Streptococcus pyogenes two-component response regulators in the temporal
      control of Mga and the Mga-regulated virulence gene emm.
AB  - We examined the role of Streptococcus pyogenes two-component response regulators
      (SptR) in expression of Mga and the Mga-regulated gene emm. Both serotype M6 and
      serotype M1 mutants in 12 of the 13 identified sptR genes exhibited levels of emm
      transcripts and Mga protein comparable to those of the wild type during
      exponential and stationary phases of growth. Thus, temporal control of these
      virulence genes does not require Spt response regulators.

PMID- 15155683
TI  - Antibody to Cryptococcus neoformans glucuronoxylomannan inhibits the release of
      capsular antigen.
AB  - Cryptococcus neoformans releases capsular polysaccharide in the supernatant of
      liquid cultures and in tissues. Significantly less glucuronoxylomannan (GXM) was
      released by C. neoformans in the presence of capsule-binding monoclonal antibody
      (MAb). MAb-mediated inhibition of GXM release may be another mechanism by which
      humoral immunity can mediate protection against this pathogen.

PMID- 15155684
TI  - Anaplasma phagocytophilum infection induces protracted neutrophil degranulation.
AB  - Anaplasma phagocytophilum-infected neutrophil degranulation could exacerbate
      inflammation. Thus, the degranulation of infected neutrophils was assayed.
      Infected neutrophils expressed CD11b and CD66b, and supernatants of infected
      neutrophils showed more proMMP-9 and MMP-9 activity than controls and continued
      to do so for > or =18 h. Degranulation-related inflammatory tissue injury may
      account for some clinical manifestations in human granulocytic anaplasmosis.

PMID- 15155685
TI  - Secretory leucoprotease inhibitor impairs Toll-like receptor 2- and 4-mediated
      responses in monocytic cells.
AB  - Secretory leucoprotease inhibitor (SLPI) is an anti-inflammatory antiprotease
      which can inhibit lipopolysaccharide-induced NF-kappaB activation. We examined
      its ability to inhibit NF-kappaB activation induced by lipoteichoic acid and
      investigated the effects of oxidation or complex formation with neutrophil
      elastase on SLPI's anti-inflammatory properties in U937 myelomonocytic cells and
      macrophages.

PMID- 15155686
TI  - CD4+ T lymphocytes from Anaplasma marginale major surface protein 2 (MSP2)
      vaccinees recognize naturally processed epitopes conserved in MSP3.
AB  - Major surface protein 2 (MSP2) and MSP3 of the persistent bovine ehrlichial
      pathogen Anaplasma marginale are immunodominant proteins that undergo antigenic
      variation. The recently completed sequence of MSP3 revealed blocks of amino acids
      in the N and C termini that are conserved with MSP2. This study tested the
      hypothesis that CD4+ T cells specific for MSP2 recognize naturally processed
      epitopes conserved in MSP3. At least one epitope in the N terminus and two in the
      C terminus of MSP2 were also processed from MSP3 and presented to CD4+ T
      lymphocytes from MSP2-immunized cattle. This T-lymphocyte response to conserved
      and partially conserved epitopes may contribute to the immunodominance of MSP2
      and MSP3.

PMID- 15155687
TI  - Growth of Piscirickettsia salmonis to high titers in insect tissue culture cells.
AB  - Piscirickettsia salmonis was grown in established insect, frog, and fish tissue
      culture cells. The yield of P. salmonis in Sf21 cells was up to 100 times that
      obtained in CHSE-214 cells, and virulence for Atlantic salmon was retained. The
      ceiling temperature for growth of P. salmonis in Sf21 cells was 24 degrees C.

PMID- 15155688
TI  - Development of environmental epidemiology in Latin America: scope, methodological
      issues, priorities.

PMID- 15155690
TI  - Women's perception of mammography screening.

PMID- 15155691
TI  - Commentary: Unravelling the mystery of variation in birthweight.

PMID- 15155692
TI  - Commentary: Socioeconomic status: more than a confounder?

PMID- 15155693
TI  - Commentary: The epidemiology of failure-to-thrive in infants.

PMID- 15155694
TI  - Severe acute respiratory syndrome: review and lessons of the 2003 outbreak.

PMID- 15155695
TI  - Lack of change in birthweights of infants by generational status among Indian,
      Pakistani, Bangladeshi, Black Caribbean, and Black African mothers in a British
      cohort study.
AB  - AIM: To test the hypothesis that an intergenerational increase would occur in
      birthweights of babies born to UK-born compared with overseas-born (migrant)
      minority women. METHOD: Live singleton births to mothers present at the 1991
      Census in a national longitudinal study were classified by mother's country of
      birth and ethnic origin as reported in the census. During 1983-2000, 52,554
      White, 1788 Indian, 1538 Pakistani, 995 Bangladeshi, 300 Black Caribbean, and 299
      Black African live singleton births were identified. Mean birthweights were
      adjusted for maternal age, socio-economic circumstances, gender, year of birth,
      and birth order. RESULTS: Adjusted mean birthweights were: 3400 g (95% CI: 3395,
      3405) for infants of UK-born White mothers; 3033 g (95% CI: 2980, 3087) of UK
      born Indian mothers and 3066 g (95% CI: 3034, 3097) of migrant Indian mothers;
      3110 g (95% CI: 3049, 3172) of UK-born Pakistani mothers and 3123 g (95% CI:
      3087, 3159) of migrant Pakistani mothers; 3026 g (95% CI: 2922, 3130) of UK-born
      Bangladeshi mothers and 3110 g (95% CI: 3076, 3145) of migrant Bangladeshi
      mothers; 3268 g (95% CI: 3177, 3359) of UK-born Black Caribbean mothers and 3238
      g (95% CI: 3089, 3388) of migrant Black Caribbean mothers; and 3167 g (95% CI:
      3004, 3330) of UK-born Black African mothers and 3302 g (95% CI: 3208, 3395) of
      migrant Black African mothers. The proportions of low birthweight infants (<2500
      g), generally greater among migrant mothers than White UK-born mothers, were
      similar by generational status within the ethnic groups. CONCLUSION: There are no
      significant differences in mean birthweights of infants by generational status
      among mothers from these main ethnic minority groups in the UK.

PMID- 15155696
TI  - Case-control study of non-Hodgkin's lymphoma and hepatitis C virus infection in
      Egypt.
AB  - BACKGROUND: Chronic infection with hepatitis C virus (HCV) has been associated in
      some studies with increased risk for B-cell non-Hodgkin's lymphoma (NHL). To
      assess this further, we conducted a case-control study in Egypt, where HCV
      prevalence is extremely high. METHODS: Cases with B-cell NHL (N = 227) were
      recruited from the National Cancer Institute of Cairo University, a major
      referral centre. Controls (N = 227) were patients with fractures being treated at
      the Kasr El-Aini Orthopaedic Hospital, from the same referral base as the cases,
      and were frequency-matched by gender, rural versus urban birthplace, and age.
      Subjects were interviewed about their medical history and possible risk factors,
      and blood samples were collected for HCV diagnostic tests. Anti-HCV and HCV RNA
      were determined by enzyme-linked immunoassay and reverse transcription-polymerase
      chain reaction, respectively. Odds ratios (OR) and 95% CI were calculated from
      logistic regression models. RESULTS: Overall, 42% of subjects were anti-HCV
      positive and 33% had HCV RNA. There was a statistically significant unadjusted
      association of HCV RNA with NHL (OR = 2.3, 95% CI: 1.5, 3.5), which differed
      slightly by gender (males: OR = 2.1, 95% CI: 1.2, 3.7 versus females: OR = 2.5,
      95% CI: 1.3, 4.8). Anti-HCV without HCV RNA was not associated with case status
      (OR = 0.9, 95% CI: 0.5, 1.6). After adjustment for age, gender, rural versus
      urban birthplace, and rural versus urban current residence, the association of
      HCV RNA with the risk of NHL remained statistically significant (OR = 2.9, 95%
      CI: 1.9, 4.5). CONCLUSIONS: These data support the hypothesis that NHL is a
      malignant outcome of chronic HCV infection.

PMID- 15155697
TI  - Commentary: Contextual effects: index construction and technique.

PMID- 15155698
TI  - Health effects of dental amalgam exposure: a retrospective cohort study.
AB  - BACKGROUND: Whether dental amalgam fillings (containing mercury) are hazardous is
      a long-standing issue, with few epidemiological investigations. Allegations have
      particularly involved nervous system disorders, such as multiple sclerosis,
      Alzheimer's disease, and chronic fatigue syndrome. This retrospective cohort
      study, the largest of its kind, contained people in the New Zealand Defence Force
      (NZDF) between 1977 and 1997. The NZDF has its own dental service, providing all
      personnel with regular and consistent treatment. Comprehensive treatment records
      are maintained and archived. METHODS: Yearly dental treatment histories,
      including amalgam filling placements, were compiled from individual records. To
      minimize amalgam exposure misclassification the cohort was restricted to people
      who, at NZDF entry, were aged <26 years and had all their posterior teeth. The
      cohort was linked with morbidity records. Data were analysed with a proportional
      hazards model, using a time-varying exposure unit of 100 amalgam surface-years.
      RESULTS: The final cohort contained 20 000 people, 84% males. Associations with
      medical diagnostic categories, particularly disorders of the nervous system and
      kidney, were examined. Of conditions allegedly associated with amalgam, multiple
      sclerosis had an adjusted hazard ratio (HR) of 1.24 (95% CI: 0.99, 1.53, P =
      0.06), but there was no association with chronic fatigue syndrome (HR = 0.98, 95%
      CI: 0.94, 1.03), or kidney diseases. There were insufficient cases for
      investigation of Alzheimer's or Parkinson's diseases. CONCLUSIONS: Results were
      generally reassuring, and provide only limited evidence of an association between
      amalgam and disease. Further follow-up of the cohort will permit investigation of
      diseases more common in the elderly.

PMID- 15155699
TI  - Income and mortality: the shape of the association and confounding New Zealand
      Census-Mortality Study, 1981-1999.
AB  - OBJECTIVE: To determine the shape of the income-mortality association, before and
      after adjusting for confounding by other socioeconomic variables. METHODS:
      Poisson regression analyses were conducted on 11.7 million years of follow-up of
      25-59 year old New Zealand census respondents spanning four separate cohort
      studies (1981-1984, 1986-1989, 1991-1994, and 1996-1999). RESULTS: Mortality
      among low-income people was approximately two times that among high-income
      people. Adjustment for potential socioeconomic confounders (marital status,
      education, car access, and neighbourhood socioeconomic deprivation) halved the
      strength of the income-mortality association, but did not appreciably change the
      shape of the association. Further adjustment for labour force status largely
      removed the income-mortality association. The association of non-transformed
      income with mortality was non-linear, with a flattening out of the slope at
      higher incomes. Both the logarithm and rank of income appeared to have a better
      linear fit with the mortality rate, although the association of mortality with
      the logarithm of income flattened out notably at low incomes. CONCLUSIONS: Much,
      but not all, of the crude association of income with mortality could be due to
      confounding. Adjusting income-mortality associations for labour force status
      (also a proxy for health status) is problematic: on the one hand, it over-adjusts
      the association as poor health will be on the pathway from income to mortality;
      on the other hand, it appropriately adjusts for both confounding by labour force
      status and reverse causation whereby income changes as a result of poor health.
      Both logarithmic and rank transformations of income have a reasonable linear fit
      with income.

PMID- 15155700
TI  - Quantitative evaluation of the effects of uncontrolled confounding by alcohol and
      tobacco in occupational cancer studies.
AB  - BACKGROUND: Uncontrolled confounding by personal exposures like smoking can limit
      the inferential power of occupational cohort studies. We developed and
      demonstrate a refinement of an existing type of sensitivity analysis, indirect
      adjustment, for evaluating the potential magnitude of confounding by alcohol and
      tobacco. Results of a large retrospective cohort study of laryngeal cancer and
      exposure to metalworking fluids (MWF) are used to illustrate the methods.
      METHODS: Data on smoking and drinking habits representative of the study cohort
      were obtained from a sample of US manufacturing workers from the 1977 National
      Health Interview Survey (NHIS). Two different mechanisms were assumed to affect
      the distribution of confounding factors between MWF exposure groups: socially
      determined and chance differences. Chance variation was investigated with Monte
      Carlo sampling from the NHIS survey distribution of smoking and drinking. An
      upper bound on systematic differences in smoking and drinking was set by assuming
      that differences between exposure groups within the same unionized blue collar
      workforce were very unlikely to be larger than differences between blue and white
      collar manufacturing workers in the NHIS data. RESULTS: Under plausibly large
      differences in smoking and drinking habits among MWF exposure groups occurring by
      either mechanism, the exposure-risk association was unlikely to have been over-
      or under-estimated by as much as 20%. CONCLUSIONS: When comparing exposure groups
      within the same working population, it is unlikely that either systematic or
      chance differences in smoking and drinking habits will cause as much as a 20%
      change in the relative risk in large studies. While this study focused on an
      occupational exposure and laryngeal cancer, there are many situations in which
      epidemiologists are concerned that unmeasured 'lifestyle factors' may differ
      among exposure groups, and it would appear that the likely confounding effect of
      such differences will often be modest.

PMID- 15155701
TI  - Height and risk of severe pre-eclampsia. A study within the Danish National Birth
      Cohort.
AB  - BACKGROUND: Pre-eclampsia shares a number of risk factors with cardiovascular
      disease (CVD). Women with recurrent pre-eclampsia or pre-eclampsia early in
      pregnancy reportedly have an increased long-term risk of CVD. Short stature is a
      risk factor for CVD but has rarely been examined in relation to pre-eclampsia.
      METHODS: We used data from 59 968 singleton live births in the Danish National
      Birth Cohort born between 1998 and 2001 to assess risk of severe pre
      eclampsia/eclampsia (296 cases) in relation to self-reported height. We examined
      the association in multiple logistic regressions stratified by parity. RESULTS:
      Among primiparas there was a weak association (compared with women <165 cm, women
      >172 cm had on OR of 0.79, 95% CI: 0.55, 1.14). Among multiparas, the tallest
      women had an adjusted OR of 0.42 (95% CI: 0.20, 0.87) of developing severe pre
      eclampsia compared with women <165 cm. The OR per centimetre was 0.94 (95% CI:
      0.91, 0.97). Self-reported pre-existing hypertension did not explain this
      association, which also persisted when the analysis was restricted to non
      overweight women. CONCLUSIONS: Short stature was associated with a higher risk of
      severe pre-eclampsia in multiparas participating in the Danish National Birth
      Cohort.

PMID- 15155702
TI  - Can we explain why Brazilian babies are becoming lighter?
AB  - BACKGROUND: We tried to explain why a marked decrease in birthweight of 122 g
      occurred over a 15-year period in Ribeirao Preto, Brazil. METHODS: Factors
      reflecting biological, social, and health care characteristics (infant gender,
      parity, maternal age, marital status, type of hospital, maternal smoking, preterm
      birth, small for gestational age [SGA], and prenatal care) were assessed on 6711
      newborns in 1978/1979 and 2838 in 1994 using multiple linear regressions.
      RESULTS: The birthweight distribution shifted to the left and the residual
      distribution of small preterm babies increased from 1.9% to 3.4%. Only marital
      status and preterm delivery would have decreased the difference in birthweight
      over time, explaining for each of them around 30 g of the 122 g. Increasing
      levels of attendance at antenatal care over time might have decreased the
      birthweight difference by 40 g. Maternal age and SGA explained little of the
      decreasing trend. Reductions in maternal smoking would have increased mean
      birthweight slightly. In stratified analysis the downward trend was more marked
      among mothers with high education (-202 g) and those delivered by caesarean
      section (-194 g). After adjusting for all those significant variables mean
      birthweight was still 74 g (95% CI: -97, -50 g) lower in 1994 than in 1978/1979.
      CONCLUSION: The trend could be explained in part by factors related to marital
      status that might reflect dysfunctional families in the Brazilian context and the
      preterm increase that might be associated with advances in medical technology.
      The high attendance at antenatal clinics or factors associated with it might have
      prevented a further decrease in birthweight. Our results may be compatible with
      the high economic development of Ribeirao Preto within Brazil, together with
      factors associated with its unfavourable lifestyle.

PMID- 15155703
TI  - Family, socioeconomic and prenatal factors associated with failure to thrive in
      the Avon Longitudinal Study of Parents and Children (ALSPAC).
AB  - BACKGROUND: The epidemiological profile of infants failing to thrive is unclear.
      The aim of this study is to investigate the prenatal and socioeconomic factors
      associated with these infants using standardized weight gain conditional on
      previous weight. METHODS: In a large UK population cohort study, 11 718 infants
      born at term in 1991-1992 with no major congenital abnormalities were identified.
      Using a weight gain criterion conditional on initial weight from birth to 6-8
      weeks, 6-8 weeks to 9 months, and birth to 9 months, the slowest gaining 5% were
      identified. RESULTS: None of the prenatal factors was associated with failure to
      thrive in the multivariable analysis nor were traditional markers of
      socioeconomic deprivation such as poor parental education or low occupational
      status. Parental height was significantly correlated with slow infant weight gain
      in both separate periods and from birth to 9 months (Pearson's r = +0.20, P <
      0.001). Eight times as many infants born to shorter parents (8.7%, 95% CI: 6.6,
      11.3) showed slow weight gain as infants born to taller parents (1.1%, 95% CI:
      0.5, 2.5). Higher parity was also related to slow infant weight gain; infants
      born in the fourth or subsequent pregnancy were twice as likely to fail to thrive
      from birth to 9 months (8.3%, 95% CI: 6.4, 10.6) as first-born infants (3.4%, 95%
      CI: 2.9, 10.6). CONCLUSIONS: Future studies need to take account of parental
      height when calculating growth standards and look at why failure to thrive is
      more common, not in poorer families but in larger families.

PMID- 15155704
TI  - Smoking, alcohol drinking, occupational exposures and social inequalities in
      hypopharyngeal and laryngeal cancer.
AB  - BACKGROUND: Social inequalities with regard to hypopharyngeal and laryngeal
      cancers are observed in many countries. Differences in alcohol and tobacco
      consumption are often proposed as an explanation for this finding. The aim of
      this work was to determine the extent to which alcohol and tobacco consumption,
      and occupational exposure, explain these inequalities. METHODS: A hospital-based
      case-control study included 504 male cases (105 with glottic, 80 with
      supraglottic, 97 with epilaryngeal, and 201 with hypopharyngeal cancers) and 242
      male controls with non-respiratory cancers. Information about sociodemographic
      characteristics, detailed alcohol and tobacco consumption, educational level, and
      occupational history were collected. Odds ratios (OR) and their 95% CI were
      computed using logistic regressions. RESULTS: When controlling for age only,
      laryngeal and hypopharyngeal cancers were strongly associated with educational
      level (OR for low versus high level = 3.22, 95% CI: 2.01, 5.18) and with all
      indicators based on occupation (OR for ever versus never manual worker = 2.54,
      95% CI: 1.78, 3.62). When adjusted for alcohol and tobacco consumption, the OR
      decreased, but remained significant for occupation (OR for ever manual worker =
      1.91, 95% CI: 1.23, 2.95). After further adjustment for occupational exposures,
      significant associations were no longer observed. Associations differed between
      subsites. CONCLUSIONS: Social inequalities observed for these cancers are not
      totally explained by alcohol and tobacco consumption; a substantial proportion
      could be attributable to occupational exposures.

PMID- 15155705
TI  - Commentary: the people know best.

PMID- 15155706
TI  - Contextual effects of social fragmentation and material deprivation on risk of
      myocardial infarction--results from the Stockholm Heart Epidemiology Program
      (SHEEP).
AB  - BACKGROUND: Socioeconomic deprivation has been suggested as a contextual feature
      of importance for cardiovascular disease and mortality, whereas the effect of
      social fragmentation has largely been studied in relation to suicide. In this
      study we examine the contextual effects of social fragmentation and material
      deprivation on the incidence of myocardial infarction (MI). METHODS: A population
      based case-control study (SHEEP). The study base included all Swedish citizens
      aged 45-70 living in the Stockholm metropolitan area. Cases (n = 1631) were all
      first events of MI during 1992-1994. Exposure information on individual risk
      factors was obtained from a questionnaire. Areas (n = 862) were classified
      according to the Townsend index, measuring material deprivation, and the Congdon
      index, measuring social fragmentation. RESULTS: We found increased incidence of
      MI in both materially deprived and socially fragmented contexts that were not due
      to confounding from individual social risk factors being more prevalent among
      subjects in deprived settings. The adjusted relative risk of MI was 2.0 (95% CI:
      1.3, 3.1) for women living in the top quartile of materially deprived areas. For
      men, the adjusted relative risk (RR) was 1.6 (95% CI: 1.2, 2.1). Women living in
      the top quartile of socially fragmented areas had an RR of MI of 1.6 (95% CI:
      1.0, 2.5) after adjustment, while the corresponding figure for men was 1.4 (95%
      CI: 1.0, 1.8). CONCLUSION: Our findings support the notion that the social
      context in which people live has an impact on the risk of coronary heart disease.
      We could not determine which of the contextual aspects under study made the most
      substantial contribution. Mutual adjustment of the two indices suggests that
      material deprivation is the dominating factor, especially for women. However, the
      indices were highly correlated (r = 0.87), and it cannot be ruled out that they
      partly measure the same underlying phenomenon.

PMID- 15155707
TI  - Weight-for-age malnutrition in Indonesian children, 1992-1999.
AB  - BACKGROUND: This article measures changes over time in Indonesia in the
      prevalence of moderate and severe child malnutrition, and examines the factors
      associated with these changes. A child with a weight-for-age Z-score below -2.0
      is classified as underweight and either moderately or severely malnourished.
      METHODS: A pooled cross-sectional dataset of 163 986 children <5 years of age
      from the 1992, 1995, 1998, and 1999 Indonesia Socioeconomic Household Surveys was
      analysed using multivariate logistic regression, and by running separate pooled
      regressions to calculate the effect of the each of the principal independent
      variables separately for each year. Robust regression techniques corrected for
      non-constant variance resulting from multilevel modelling. RESULTS: The overall
      percentage of children <5 years that are underweight decreased from 37.7% in 1992
      to 28.5% in 1999. Nearly all of the gains occurred in children over one year of
      age. Child nutritional status improved for all major social groups in Indonesia.
      There was no measurable general effect of the 1997-1999 East Asian economic
      crisis on levels of underweight children. CONCLUSIONS: Disparities among social
      and economic groups have narrowed over time in Indonesia; the relatively high
      risk of male children compared with females has also decreased. Maternal
      education and economic status-as measured by quintile of adjusted per-capita
      household expenditures-have continued to be very strong predictors of children's
      nutritional outcomes.

PMID- 15155708
TI  - Neonatal tetanus incidence in China, 1996-2001, and risk factors for neonatal
      tetanus, Guangxi Province, China.
AB  - BACKGROUND: In China during 1995-1996 widespread tetanus toxoid (TT) mass
      vaccination of women of childbearing age in high-risk areas was conducted and
      neonatal tetanus (NT) surveillance was initiated as part of NT elimination
      efforts. Despite a subsequent decrease in the estimated rate of NT, the NT
      disease burden remains high in poorer areas of China. METHODS: To describe the
      recent epidemiology of NT in China and estimate its risk, we analysed national
      surveillance data in China 1996-2001 and conducted a case-control study in one
      high-risk county (Bobai): 60 hospitalized cases were sex- and calendar-birth year
      matched to 60 controls from the same or neighbouring villages. RESULTS: Reported
      national annual NT incidence decreased from 0.21/1000 live births (LB) in 1997 to
      0.16/1000 LB in 2001. Case mothers were more likely to be aged >30 years (odds
      ratio [OR] = 6; 95% CI: 2.2, 20.2), unschooled (OR = 3.2; 95% CI: 1.1, 11.6), and
      with an annual income of <1000 yuan ($125 USD) (OR = 6.0; 95% CI: 1.9, 25.6).
      Only 28% of control mothers and 12% of case mothers reported any TT vaccination.
      In multivariate analysis, relative to hospital delivery, cases had a 64-fold
      increased odds of home delivery by a family member or neighbour (95% CI: 8.4,
      982.2), and a 13-fold increased odds of home delivery by a traditional birth
      attendant (95% CI: 1.6, 322.6). CONCLUSIONS: Improved access to clean deliveries
      in high-risk areas is critically needed in China. Nonetheless, targeted TT
      vaccination appears to have helped reduce NT incidence in China.

PMID- 15155709
TI  - Community based participatory research: a promising approach for increasing
      epidemiology's relevance in the 21st century.
AB  - Despite the advances of modern epidemiology, the field remains limited in its
      ability to explain why certain outcomes occur and to generate the kind of
      findings that can be translated into programmes or policies to improve health.
      Creating community partnerships such that community representatives participate
      in the definition of the research problem, interpretation of the data, and
      application of the findings may help address these concerns. Community based
      participatory research (CBPR) is a framework epidemiologists can apply to their
      studies to gain a better understanding of the social context in which disease
      outcomes occur, while involving community partners in the research process, and
      insuring that action is part of the research process itself. The utility of CBPR
      principles has been particularly well demonstrated by environmental
      epidemiologists who have employed this approach in data gathering on exposure
      assessment and advancing environmental justice. This article provides examples of
      how popular epidemiology applies many of CBPR's key principles. At this critical
      juncture in its history, epidemiology may benefit from further incorporating
      CBPR, increasing the field's ability to study and understand complex community
      health problems, insure the policy and practice relevance of findings, and assist
      in using those findings to help promote structural changes that can improve
      health and prevent disease.

PMID- 15155710
TI  - Respiratory sinus arrhythmia in freely moving and anesthetized rats.
AB  - Heart rate increases during inspiration and slows during postinspiration; this
      respiratory sinus arrhythmia helps match pulmonary blood flow to lung inflation
      and maintain an appropriate diffusion gradient of oxygen in the lungs. This
      cardiorespiratory pattern is found in neonatal and adult humans, baboons, dogs,
      rabbits, and seals. Respiratory sinus arrhythmia occurs mainly due to inhibition
      of cardioinhibitory parasympathetic cardiac vagal neurons during inspiration.
      Surprisingly, however, a recent study in anesthetized rats paradoxically found an
      enhancement of cardiac vagal activity during inspiration, suggesting that rats
      have an inverted respiratory sinus arrhythmia (Rentero N, Cividjian A, Trevaks D,
      Pequignot JM, Quintin L, and McAllen RM. Am J Physiol Regul Integr Comp Physiol
      283: R1327-R1334, 2002). To address this controversy, this study examined
      respiratory sinus arrhythmia in conscious freely moving rats and tested whether
      the commonly used experimental anesthetics urethane, pentobarbital sodium, or
      ketamine-xylazine alter respiratory sinus arrhythmia. Heart rate significantly
      increased 21 beats/min during inspiration in conscious rats, a pattern similar to
      the respiratory sinus arrhythmia that occurs in other species. However,
      anesthetics altered normal respiratory sinus arrhythmia. Ketamine-xylazine (87
      mg/kg and 13 mg/kg) depressed and pentobarbital sodium (60 mg/kg) abolished
      normal respiratory sinus arrhythmia. Urethane (1 g/kg) inverted the
      cardiorespiratory pattern so that heart rate significantly decreased during
      inspiration. Our study demonstrates that heart rate normally increases during
      inspiration in conscious, freely moving rats, similar to the respiratory sinus
      arrhythmia pattern that occurs in other species but that this pattern is
      disrupted in the presence of general anesthetics, including inversion in the case
      of urethane. The presence and consequences of anesthetics need to be considered
      in studying the parasympathetic control of heart rate.

PMID- 15155711
TI  - Stress-related genomic responses during the course of heat acclimation and its
      association with ischemic-reperfusion cross-tolerance.
AB  - Acclimation to heat is a biphasic process involving a transient perturbed phase
      followed by a long lasting period during which acclimatory homeostasis is
      developed. In this investigation, we used cDNA stress microarray (Clontech
      Laboratory) to characterize the stress-related genomic response during the course
      of heat acclimation and to test the hypotheses that 1) heat acclimation
      influences the threshold of activation of protective molecular signaling, and 2)
      heat-acclimation-mediated ischemic-reperfusion (I/R) protection is coupled with
      reprogrammed gene expression leading to altered capacity or responsiveness of
      protective-signaling pathways shared by heat and I/R cytoprotective systems. Rats
      were acclimated at 34 degrees C for 0, 2, and 30 days. 32P-labeled RNA samples
      prepared from the left ventricles of rats before and after subjection to heat
      stress (HS; 2 h, 41 degrees C) or after I/R insult (ischemia: 75%, 45 min;
      reperfusion: 30 min) were hybridized onto the array membranes. Confirmatory RT
      PCR of selected genes conducted on samples taken at 0, 30, and 60 min after HS or
      total ischemia was used to assess the promptness of the transcriptional response.
      Cluster analysis of the expressed genes indicated that acclimation involves a
      "two-tier" defense strategy: an immediate transient response peaking at the
      initial acclimating phase to maintain DNA and cellular integrity, and a sustained
      response, correlated with slowly developed adaptive, long-lasting cytoprotective
      signaling networks involving genes encoding proteins that are essential for the
      heat-shock response, antiapoptosis, and antioxidation. Gene activation was stress
      specific. Faster activation and suppression of signaling pathways shared by HS
      and I/R stressors probably contribute to heat-acclimation I/R cross-tolerance.

PMID- 15155712
TI  - Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin.
AB  - Vasoactive intestinal peptide (VIP) is known to induce histamine release in human
      skin and to include a nitric oxide (NO)-dependent dilation in several other
      vascular beds. However, the relative contribution of histamine and NO to VIP
      mediated vasodilation in human skin is unknown. Forty-three subjects volunteered
      to participate in two studies designed to examine the mechanism of VIP-mediated
      vasodilation in human skin. Study 1 examined the contribution of NO in the skin
      blood flow response to eight doses of VIP ranging from 25 to 800 pmol. In
      addition, study 1 examined a specific role for NO in VIP-mediated dilation. Study
      2 examined the relative contribution of NO and histamine to VIP-mediated dilation
      via H1 and H2 histamine receptors. Infusions were administered to skin sites via
      intradermal microdialysis. Red blood cell flux was measured by using laser
      Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC; LDF/mean
      arterial pressure) was calculated and normalized to maximal vasodilation. VIP
      mediated vasodilation includes a NO-dependent component at doses above 100 pmol,
      where NO synthase inhibition significantly attenuates CVC (P < 0.05). Inhibition
      of H1 receptors attenuates the rise in CVC to exogenous VIP (P < 0.05); however,
      combined H1-receptor inhibition and NO synthase inhibition further reduced VIP
      mediated vasodilation compared with either H1 inhibition or NO synthase
      inhibition alone (P < 0.05). In contrast to H1-receptor inhibition, H2-receptor
      inhibition did not affect vasodilation to exogenous VIP. Thus, in human skin, VIP
      mediated vasodilation includes a NO-dependent component that could not be
      explained by H1- and H2-receptor activation.

PMID- 15155713
TI  - Effect of changing the gravity vector on respiratory output and control.
AB  - We studied the respiratory output in five subjects exposed to parabolic flights
      [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)]
      and when switching from sitting to supine (legs bent at the knees). Despite
      differences in total respiratory compliance (highest at 0 Gz and in supine and
      minimum at 1.8 Gz), no significant changes in elastic inspiratory work were
      observed in the various conditions, except when comparing 1.8 Gz with 1 Gz
      (subjects were in the seated position in all circumstances), although the elastic
      work had an inverse relationship with total respiratory compliance that was
      highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz,
      lung resistance (airways plus lung tissue) increased significantly by 52% in the
      supine but slightly decreased at 0 Gz. We calculated, for each condition, the
      tidal volume changes based on the energy available in the preceding phase and
      concluded that an increase in inspiratory muscle output occurs when respiratory
      load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the
      opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes,
      ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%),
      reflecting an increase in mean inspiratory flow rate, tidal volume, and
      respiratory frequency, while ventilation decreased (approximately -14%), shifting
      to supine posture (transition time approximately 15 s). These data suggest a
      remarkable feature in the mechanical arrangement of the respiratory system such
      that it can maintain the ventilatory output with small changes in inspiratory
      muscle work in face of considerable changes in configuration and mechanical
      properties.

PMID- 15155714
TI  - Prolonged exercise to fatigue in humans impairs skeletal muscle Na+-K+-ATPase
      activity, sarcoplasmic reticulum Ca2+ release, and Ca2+ uptake.
AB  - Prolonged exhaustive submaximal exercise in humans induces marked metabolic
      changes, but little is known about effects on muscle Na+-K+-ATPase activity and
      sarcoplasmic reticulum Ca2+ regulation. We therefore investigated whether these
      processes were impaired during cycling exercise at 74.3 +/- 1.2% maximal O2
      uptake (mean +/- SE) continued until fatigue in eight healthy subjects (maximal
      O2 uptake of 3.93 +/- 0.69 l/min). A vastus lateralis muscle biopsy was taken at
      rest, at 10 and 45 min of exercise, and at fatigue. Muscle was analyzed for in
      vitro Na+-K+-ATPase activity [maximal K+-stimulated 3-O-methylfluorescein
      phosphatase (3-O-MFPase) activity], Na+-K+-ATPase content ([3H]ouabain binding
      sites), sarcoplasmic reticulum Ca2+ release rate induced by 4 chloro-m-cresol,
      and Ca2+ uptake rate. Cycling time to fatigue was 72.18 +/- 6.46 min. Muscle 3-O
      MFPase activity (nmol.min(-1).g protein(-1)) fell from rest by 6.6 +/- 2.1% at 10
      min (P <0.05), by 10.7 +/- 2.3% at 45 min (P <0.01), and by 12.6 +/- 1.6% at
      fatigue (P <0.01), whereas 3[H]ouabain binding site content was unchanged. Ca2+
      release (mmol.min(-1).g protein(-1)) declined from rest by 10.0 +/- 3.8% at 45
      min (P <0.05) and by 17.9 +/- 4.1% at fatigue (P < 0.01), whereas Ca2+ uptake
      rate fell from rest by 23.8 +/- 12.2% at fatigue (P=0.05). However, the decline
      in muscle 3-O-MFPase activity, Ca2+ uptake, and Ca2+ release were variable and
      not significantly correlated with time to fatigue. Thus prolonged exhaustive
      exercise impaired each of the maximal in vitro Na+-K+-ATPase activity, Ca2+
      release, and Ca2+ uptake rates. This suggests that acutely downregulated muscle
      Na+, K+, and Ca2+ transport processes may be important factors in fatigue during
      prolonged exercise in humans.

PMID- 15155715
TI  - Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle:
      influence of physical activity and gender.
AB  - The protein and mRNA levels of several muscle lipid-binding proteins and the
      activity and mRNA level of muscle lipoprotein lipase (mLPL) were investigated in
      healthy, nonobese, nontrained (NT), moderately trained, and endurance-trained
      (ET) women and men. FAT/CD36 protein level was 49% higher (P < 0.05) in women
      than in men, irrespective of training status, whereas FAT/CD36 mRNA was only
      higher (P < 0.05) in women than in men in NT subjects (85%). Plasma membrane
      bound fatty acid binding protein (FABPpm) content was higher in ET men compared
      with all other groups, whereas training status did not affect FABPpm content in
      women. FABPpm mRNA was higher (P < 0.05) in NT women than in ET women and NT men.
      mLPL activity was not different between gender, but mLPL mRNA was 160% higher (P
      < 0.001) in women than in men. mLPL activity was 48% higher (P < 0.05) in ET than
      in NT subjects, irrespective of gender, in accordance with 49% higher (P < 0.05)
      mLPL mRNA in ET than in NT subjects. A 90-min exercise bout induced an increase
      (P < 0.05) in FAT/CD36 mRNA (approximately 25%) and FABPpm mRNA (approximately
      15%) levels in all groups. The present study demonstrated that, in the NT state,
      women had higher muscle mRNA levels of several proteins related to muscle lipid
      metabolism compared with men. In the ET state, only the gender difference in mLPL
      mRNA persisted. FAT/CD36 protein in muscle was higher in women than in men,
      irrespective of training status. These findings may help explain gender
      differences in lipid metabolism and, furthermore, suggest that the balance
      between gene transcription, translation, and possibly breakdown of several
      proteins in muscle lipid metabolism depend on gender.

PMID- 15155716
TI  - Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest-to
      mild and mild-to-moderate forearm exercise transitions in humans.
AB  - Controversy exists regarding the contribution of a rapid vasodilatory
      mechanism(s) to immediate exercise hyperemia. Previous in vivo investigations
      have exclusively examined rest-to-exercise (R-E) transitions where both the
      muscle pump and early vasodilator mechanisms may be activated. To isolate
      vasodilatory onset, the present study investigated the onset of exercise
      hyperemia in an exercise-to-exercise (E-E) transition, where no further increase
      in muscle pump contribution would occur. Eleven subjects lay supine and performed
      a step increase from rest to 3 min of mild (10% maximal voluntary contraction),
      rhythmic, dynamic forearm handgrip exercise, followed by a further step to
      moderate exercise (20% maximal voluntary contraction) in each of arm above
      (condition A) or below (condition B) heart level. Beat-by-beat measures of
      brachial arterial blood flow (Doppler ultrasound) and blood pressure (arterial
      tonometry) were performed. We observed an immediate increase in forearm vascular
      conductance in E-E transitions, and the magnitude of this increase matched that
      of the R-E transitions within each of the arm positions (condition A: E-E, 52.8
      +/- 10.7 vs. R-E, 60.3 +/- 11.7 ml.min(-1).100 mmHg(-1), P = 0.66; condition B: E
      E, 43.2 +/- 12.8 vs. R-E, 33.9 +/- 8.2 ml.min(-1).100 mmHg(-1), P = 0.52).
      Furthermore, changes in forearm vascular conductance were identical between R-E
      and E-E transitions over the first nine contraction-relaxation cycles in
      condition A. The immediate and identical increase in forearm vascular conductance
      in R-E and E-E transitions within arm positions provides strong evidence that
      rapid vasodilation contributes to immediate exercise hyperemia in humans.
      Specific vasodilatory mechanisms responsible remain to be determined.

PMID- 15155717
TI  - Effects of carbohydrate supplementation on performance and carbohydrate oxidation
      after intensified cycling training.
AB  - To study the effects of carbohydrate (CHO) supplementation on performance changes
      and symptoms of overreaching, six male endurance cyclists completed 1 wk of
      normal (N), 8 days of intensified (ITP), and 2 wk of recovery training (R) on two
      occasions in a randomized crossover design. Subjects completed one trial with a
      6% CHO solution provided before and during training and a 20% solution in the 1 h
      postexercise (H-CHO trial). On the other occasion, subjects consumed a 2% CHO
      solution at the same time points (L-CHO). A significant decline in time to
      fatigue at approximately 63% maximal power output (H-CHO: 17 +/- 3%; L-CHO: 26 +/
      7%) and a significant increase in mood disturbance occurred in both trials after
      ITP. The decline in performance was significantly greater in the L-CHO trial.
      After ITP, a significant decrease in estimated muscle glycogen oxidation (H-CHO:
      N 49.3 +/- 2.9 kcal/30 min, ITP 32.6 +/- 3.4 kcal/30 min; L-CHO: N 49.1 +/- 30
      kcal/30 min, ITP 39.0 +/- 5.6 kcal/30 min) and increase in fat oxidation (H-CHO:
      N 16.3 +/- 2.4 kcal/30 min, ITP 27.8 +/- 2.3 kcal/30 min; L-CHO: N 16.9 +/- 2.6
      kcal/30 min, ITP: 25.4 +/- 3.5 kcal/30 min) occurred alongside significant
      increases in glycerol and free fatty acids and decreases in free triglycerides in
      both trials. An interaction effect was observed for submaximal plasma
      concentrations of cortisol and epinephrine, with significantly greater reductions
      in these stress hormones in L-CHO compared with H-CHO after ITP. These findings
      suggest that CHO supplementation can reduce the symptoms of overreaching but
      cannot prevent its development. Decreased endocrine responsiveness to exercise
      may be implicated in the decreased performance and increased mood disturbance
      characteristic of overreaching.

PMID- 15155718
TI  - Myogenic protein expression before and after resistance loading in 26- and 64-yr
      old men and women.
AB  - Based on the growing body of evidence implicating an important role for myogenic
      regulatory factors (MRFs) in the adaptive responses of skeletal muscle to
      mechanical load, we tested the hypothesis that protein concentrations of MRFs as
      well as cell cycle proteins (i.e., cyclins and cyclin-dependent kinase
      inhibitors) would be altered after heavy leg resistance exercise (RE). Because we
      and others, however, have shown a blunted adaptive response to long-term
      resistance training in older (O) women [females (F)] compared with men (M), we
      also tested the hypothesis that these myogenic responses to RE would be
      influenced by age and gender. Twenty-two younger (Y) adults (20-35 yr, 11 YF, 11
      YM) and 20 O adults (60-75 yr, 9 OF, 11 OM) consented to vastus lateralis muscle
      biopsy before and 24 h after a bout of RE using a regimen known to induce
      myofiber hypertrophy when performed 2-3 days/wk for several weeks (3 sets of 80%
      one-repetition maximum for squat, leg press, and knee extension). Protein
      concentrations of MRFs (MyoD, myogenin, myf-6), cyclin D1, cyclin B1, alpha
      actin, and the cyclin-dependent kinase inhibitor p27kip were determined by
      immunoblotting. Data were analyzed by using age x gender x load repeated-measures
      ANOVA. Myogenin expression was 44% higher (P <0.05) in O compared with Y, and myf
      6 tended to be higher in OF compared with YF (95%, P=0.059). A significant gender
      x load interaction indicated that, in F, RE led to a reduction in p27kip (20%;
      P<0.05), which was driven mainly by a 27% drop in OF. Levels of cyclin D1, cyclin
      B1, MyoD, myf-6, and alpha-actin were not influenced by age, gender, or loading.
      We report a novel finding in humans of markedly higher myogenin protein content
      in older sedentary muscle. The results do not, however, support the hypothesis
      that myogenic protein expression is altered 24 h after RE, irrespective of age or
      gender. Although the time point of postexercise muscle biopsy could be viewed as
      too early to capture maximal effects for most of these proteins, the significant
      decline in p27kip concentration found in OF suggests that mechanical load may
      provide one means of overcoming the inhibitory influence of p27kip.

PMID- 15155719
TI  - Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in
      pancreatic cancer cells.
AB  - One reason why pancreatic cancer is so aggressive and unresponsive to treatments
      is its resistance to apoptosis. We report here that reactive oxygen species (ROS)
      are a prosurvival, antiapoptotic factor in pancreatic cancer cells. Human
      pancreatic adenocarcinoma MIA PaCa-2 and PANC-1 cells generated ROS, which was
      stimulated by growth factors (serum, insulin-like growth factor I, or fibroblast
      growth factor-2). Growth factors also stimulated membrane NAD(P)H oxidase
      activity in these cells. Both intracellular ROS and NAD(P)H oxidase activity were
      inhibited by antioxidants tiron and N-acetylcysteine and the inhibitor of
      flavoprotein-dependent oxidases, diphenylene iodonium, but not by inhibitors of
      various other ROS-generating enzymes. Using Rho(0) cells deficient in
      mitochondrial DNA, we showed that a nonmitochondrial NAD(P)H oxidase is a major
      source of growth factor-induced ROS in pancreatic cancer cells. Among proteins
      that have been implicated in NAD(P)H oxidase activity, MIA PaCa-2 and PANC-1
      cells do not express the phagocytic gp91(phox) subunit but express several
      nonphagocytic oxidase (NOX) isoforms. Transfection with Nox4 antisense
      oligonucleotide inhibited NAD(P)H oxidase activity and ROS production in MIA PaCa
      2 and PANC-1 cells. Inhibiting ROS with the antioxidants, Nox4 antisense, or
      MnSOD overexpression all stimulated apoptosis in pancreatic cancer cells as
      measured by internucleosomal DNA fragmentation, phosphatidylserine
      externalization, cytochrome c release, and effector caspase activation. The
      results show that growth factor-induced ROS produced by NAD(P)H oxidase (probably
      Nox4) protect pancreatic cancer cells from apoptosis. This mechanism may play an
      important role in pancreatic cancer resistance to treatment and thus represent a
      novel therapeutic target.

PMID- 15155720
TI  - Structural basis for the catalytic activity of human serine/threonine protein
      phosphatase-5.
AB  - Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that
      regulate cell growth and cellular responses to stress. Here we report the crystal
      structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. From this
      structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein
      substrates, which requires the precise positioning of two metal ions within a
      conserved Asp271-M1:M2-W1-His427-His304-Asp274 catalytic motif (where M1 and M2
      are metals and W1 is a water molecule). The structure of PP5c provides a
      structural basis for explaining the exceptional catalytic proficiency of protein
      phosphatases, which are among the most powerful known catalysts. Resolution of
      the entire C terminus revealed a novel subdomain, and the structure of the PP5c
      should also aid development of type-specific inhibitors.

PMID- 15155721
TI  - The catalytic role of aspartate in a short strong hydrogen bond of the Asp274
      His32 catalytic dyad in phosphatidylinositol-specific phospholipase C can be
      substituted by a chloride ion.
AB  - Phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis
      catalyzes the cleavage of the phosphorus-oxygen bond in phosphatidylinositol. The
      focus of this work is to dissect the roles of the carboxylate side chain of
      Asp(274) in the Asp(274)-His(32) dyad, where a short strong hydrogen bond (SSHB)
      was shown to exist based on NMR criteria. A regular hydrogen bond (HB) was
      observed in D274N, and no low field proton resonance was detected for D274E and
      D274A. Comparison of the activity of wild type, D274N, and D274A suggested that
      the regular HB contributes significantly (approximately 4 kcal/mol) to catalysis,
      whereas the SSHB contributes only an additional 2 kcal/mol. The mutant D274E
      displays high activity similar to wild type, suggesting that the negative charge
      is sufficient for the catalytic role of Asp(274). To further support this
      interpretation and rule out possible contribution of regular HB or SSHB in D274E,
      we showed that the activity of D274G can be rescued by exogenous chloride ions to
      a level comparable with that of D274E. Comparison between different anions
      suggested that the ability of an anion to rescue the activity is due to the size
      and the charge of the anion not the property as a HB acceptor. In conclusion, a
      major fraction of the functional role of Asp(274) in the Asp(274)-His(32) dyad
      can be attributed to a negative charge (as in D274E and D274G-Cl(-)), and the
      SSHB in the wild type enzyme provides minimal contribution to catalysis. These
      results represent novel insight for an Asp-His catalytic dyad and for the
      mechanism of phosphatidylinositol-specific phospholipase C.

PMID- 15155722
TI  - Unique features of the sodC-encoded superoxide dismutase from Mycobacterium
      tuberculosis, a fully functional copper-containing enzyme lacking zinc in the
      active site.
AB  - The sodC-encoded Mycobacterium tuberculosis superoxide dismutase (SOD) shows high
      sequence homology to other members of the copper/zinc-containing SOD family. Its
      three-dimensional structure is reported here, solved by x-ray crystallography at
      1.63-A resolution. Metal analyses of the recombinant protein indicate that the
      native form of the enzyme lacks the zinc ion, which has a very important
      structural and functional role in all other known enzymes of this class. The
      absence of zinc within the active site is due to significant rearrangements in
      the zinc subloop, including deletion or mutation of the metal ligands His115 and
      His123. Nonetheless, the enzyme has a catalytic rate close to the diffusion
      limit; and unlike all other copper/zinc-containing SODs devoid of zinc, the
      geometry of the copper site is pH-independent. The protein shows a novel dimer
      interface characterized by a long and rigid loop, which confers structural
      stability to the enzyme. As the survival of bacterial pathogens within their host
      critically depends on their ability to recruit zinc in highly competitive
      environments, we propose that the observed structural rearrangements are required
      to build up a zinc-independent but fully active and stable copper-containing SOD.

PMID- 15155723
TI  - The host cell MAP kinase ERK-2 regulates viral assembly and release by
      phosphorylating the p6gag protein of HIV-1.
AB  - The host cell MAP kinase ERK-2 incorporated within human immunodeficiency virus
      type 1 particles plays a critical role in virus infectivity by phosphorylating
      viral proteins. Recently, a fraction of the virus incorporated late (L) domain
      containing p6(gag) protein, which has an essential function in the release of
      viral particles from the cell surface, was reported to be phosphorylated by an
      unknown virus-associated cellular protein kinase (Muller, B., Patschinsky, T.,
      and Krausslich, H. G. (2002) J. Virol. 76, 1015-1024). The present study
      demonstrates the contribution of the MAP kinase ERK-2 in p6(gag) phosphorylation.
      According to mutational analysis, a single ERK-2-phosphorylated threonine
      residue, belonging to a highly conserved phosphorylation MAP kinase consensus
      site, was identified at position 23 within p6(gag). Substitution by an alanine of
      the Thr(23) phosphorylable residue within the pNL4.3 molecular clone was found to
      decrease viral release from various cell types. As observed from electron
      microscopy experiments, most virions produced from this molecular clone remained
      incompletely separated from the host cell membrane with an immature morphology
      and displayed a reduced infectivity in single round infection experiments.
      Analysis of protein processing by Western blotting experiments revealed an
      incomplete Pr55(gag) maturation and a reduction in the virion-associated reverse
      transcriptase proteins was observed that was not related to differences in
      intracellular viral protein expression. Altogether, these data suggest that
      phosphorylation of p6(gag) protein by virus-associated ERK-2 is involved in the
      budding stage of HIV-1 life cycle.

PMID- 15155724
TI  - Liver fatty acid-binding protein gene ablation inhibits branched-chain fatty acid
      metabolism in cultured primary hepatocytes.
AB  - Whereas the role of liver fatty acid-binding protein (L-FABP) in the uptake,
      transport, mitochondrial oxidation, and esterification of normal straight-chain
      fatty acids has been studied extensively, almost nothing is known regarding the
      function of L-FABP in peroxisomal oxidation and metabolism of branched-chain
      fatty acids. Therefore, phytanic acid (most common dietary branched-chain fatty
      acid) was chosen to address these issues in cultured primary hepatocytes isolated
      from livers of L-FABP gene-ablated (-/-) and wild type (+/+) mice. These studies
      provided three new insights: First, L-FABP gene ablation reduced maximal, but not
      initial, uptake of phytanic acid 3.2-fold. Initial uptake of phytanic acid uptake
      was unaltered apparently due to concomitant 5.3-, 1.6-, and 1.4-fold up
      regulation of plasma membrane fatty acid transporter/translocase proteins
      (glutamic-oxaloacetic transaminase, fatty acid transport protein, and fatty acid
      translocase, respectively). Second, L-FABP gene ablation inhibited phytanic acid
      peroxisomal oxidation and microsomal esterification. These effects were
      consistent with reduced cytoplasmic fatty acid transport as evidenced by
      multiphoton fluorescence photobleaching recovery, where L-FABP gene ablation
      reduced the cytoplasmic, but not membrane, diffusional component of NBD-stearic
      acid movement 2-fold. Third, lipid analysis of the L-FABP gene-ablated
      hepatocytes revealed an altered fatty acid phenotype. Free fatty acid and
      triglyceride levels were decreased 1.9- and 1.6-fold, respectively. In summary,
      results with cultured primary hepatocytes isolated from L-FABP (+/+) and L-FABP (
      /-) mice demonstrated for the first time a physiological role of L-FABP in the
      uptake and metabolism of branched-chain fatty acids.

PMID- 15155725
TI  - A yeast strain lacking lipid particles bears a defect in ergosterol formation.
AB  - Lipid particles of the yeast Saccharomyces cerevisiae are storage compartments
      for triacylglycerols (TAG) and steryl esters (STE). Four gene products, namely
      the TAG synthases Dga1p and Lro1p, and the STE synthases Are1p and Are2p
      contribute to storage lipid synthesis. A yeast strain lacking the four respective
      genes is devoid of lipid particles thus providing a valuable tool to study the
      physiological role of storage lipids and lipid particles. Using a
      dga1lro1are1are2 quadruple mutant transformed with plasmids bearing inducible
      DGA1, LRO1, or ARE2 we demonstrate that TAG synthesis contributes more
      efficiently to lipid particle proliferation than synthesis of STE. Moreover, we
      show that proteins typically located to lipid particles in wild type such as
      Erg1p, Erg6p, Erg7p, and Ayr1p are refined to microsomal fractions of the
      dga1lro1are1are2 quadruple mutant. This result confirms the close relationship
      between lipid particles and endoplasmic reticulum. Most interestingly, the amount
      of the squalene epoxidase Erg1p, which is dually located in lipid particles and
      endoplasmic reticulum of wild type, is decreased in the quadruple mutant, whereas
      amounts of other lipid particle proteins tested were not reduced. This decrease
      is not caused by down-regulation of ERG1 transcription but by the low stability
      of Erg1p in the quadruple mutant. Because a similar effect was also observed in
      are1are2 mutants this finding can be mainly attributed to the lack of STE. The
      quadruple mutant, however, was more sensitive to terbinafine, an inhibitor of
      Erg1p, than the are1are2 strain suggesting that the presence of TAG and/or intact
      lipid particles has an additional protective effect. In a strain lacking the two
      STE synthases, Are1p and Are2p, incorporation of ergosterol into the plasma
      membrane was reduced, although the total cellular amount of free ergosterol was
      higher in the mutant than in wild type. Thus, an esterification/deacylation
      mechanism appears to contribute to the supply of ergosterol to the plasma
      membrane.

PMID- 15155726
TI  - Structural and biochemical studies of the substrate selectivity of carnitine
      acetyltransferase.
AB  - Carnitine acyltransferases catalyze the exchange of acyl groups between coenzyme
      A (CoA) and carnitine. They have important roles in many cellular processes,
      especially the oxidation of long-chain fatty acids, and are attractive targets
      for drug discovery against diabetes and obesity. These enzymes are classified
      based on their substrate selectivity for short-chain, medium-chain, or long-chain
      fatty acids. Structural information on carnitine acetyltransferase suggests that
      residues Met-564 and Phe-565 may be important determinants of substrate
      selectivity with the side chain of Met-564 located in the putative binding pocket
      for acyl groups. Both residues are replaced by glycine in carnitine
      palmitoyltransferases. To assess the functional relevance of this structural
      observation, we have replaced these two residues with small amino acids by
      mutagenesis, characterized the substrate preference of the mutants, and
      determined the crystal structures of two of these mutants. Kinetic studies
      confirm that the M564G or M564A mutation is sufficient to increase the activity
      of the enzyme toward medium-chain substrates with hexanoyl-CoA being the
      preferred substrate for the M564G mutant. The crystal structures of the M564G
      mutant, both alone and in complex with carnitine, reveal a deep binding pocket
      that can accommodate the larger acyl group. We have determined the crystal
      structure of the F565A mutant in a ternary complex with both the carnitine and
      CoA substrates at a 1.8-A resolution. The F565A mutation has minor effects on the
      structure or the substrate preference of the enzyme.

PMID- 15155727
TI  - Unexpected structure of the Ca2+-regulatory region from soybean calcium-dependent
      protein kinase-alpha.
AB  - Calcium-dependent protein kinases (CDPKs) are an extensive class of multidomain
      Ca(2+)-regulated enzymes from plants and protozoa. In vivo the so-called
      calmodulin-like domain (CLD) of CDPK binds intramolecularly to the junction
      domain (JD), which exhibits both kinase-inhibitory and CLD binding properties.
      Here we report the high resolution solution structure of the calcium-regulatory
      region from soybean CDPK-alpha determined in the presence of a peptide
      encompassing the JD. The structure of both lobes of CLD resembles that of related
      helix-loop-helix Ca(2+)-binding proteins. NMR chemical shift mapping studies
      demonstrate that the JD induces significant structural changes in isolated Ca(2+)
      CLD, particularly the C-terminal domain, although a stable complex is not formed.
      A CLD solution structure calculated on the basis of NMR data and long range
      fluorescence resonance energy transfer distances reveals an activated state with
      both lobes positioned side by side, similar to calcineurin B rather than
      calmodulin, highlighting the possible pitfall of assigning function purely from
      sequence information.

PMID- 15155728
TI  - Newly discovered neutral glycosphingolipids in aureobasidin A-resistant
      zygomycetes: Identification of a novel family of Gala-series glycolipids with
      core Gal alpha 1-6Gal beta 1-6Gal beta sequences.
AB  - We found for the first time that Zygomycetes species showed resistance to
      Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids
      (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a
      typical Zygomycetes species. Their structures were completely determined by
      compositional sugar, fatty acid, and sphingoid analyses, methylation analysis,
      matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and
      (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS),
      Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal
      beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal
      beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of
      24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4
      hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the
      glycosylinositolphosphoceramide families that are the major GSLs components in
      fungi were not detected in Zygomycetes at all. This seems to be the reason that
      Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our
      results indicate that the biosynthetic pathway for GSLs in Zygomycetes is
      significantly different from those in other fungi and suggest that any inhibitor
      of this pathway may be effective for mucormycosis, which is a serious pathogenic
      disease for humans.

PMID- 15155729
TI  - The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand
      regulated signaling through Gi, Gq, and G12/13 proteins but constitutive
      signaling only through Gi and G12/13 proteins.
AB  - Open reading frame 74 (ORF74) of many gamma(2)-herpesviruses encodes a CXC
      chemokine receptor. The molecular pharmacological profile of ORF74 from
      herpesvirus saimiri, ECRF3, is characterized here and compared with that of the
      well known ORF74 from human herpesvirus 8 (HHV8). The ECRF3 receptor bound the so
      called ELR (Glu-Leu-Arg) CXC chemokines (125)I-CXCL1/GRO alpha, (125)I-CXCL6/GCP
      2, and (125)I-CXCL8/interleukin-8 with high affinity; but in contrast to ORF74
      from HHV8, it did not bind the non-ELR CXC chemokine (125)I-CXCL10/IP10.
      Interestingly, the B(max) value for CXCL6/GCP-2 was 3-fold higher than the
      capacity for maximal binding of CXCL1/GRO alpha to ECRF3 and 85-fold higher than
      that of CXCL8/interleukin-8, despite similar affinities. Like ORF74 from HHV8,
      ECRF3 activated a broad range of pathways (G(q), G(i), and G(12/13) as well as
      the cAMP response element-binding protein, NF-kappa B, NFAT, and serum response
      element transcription factors) in a ligand-regulated manner, with CXCL6/GCP-2
      being the most potent and efficacious agonist. ECRF3 signaled constitutively
      through G(i) and G(12/13), but surprisingly not through G(q). At the level of
      transcription factor activation, the serum response element was activated
      constitutively by ECRF3, whereas cAMP response element-binding protein, NFAT, and
      NF-kappa B were only ligand-regulated. The maximal signaling capacities were
      similar for the two receptors; however, the ligand-regulated signaling was
      responsible for the major part of the total ECRF3 signaling and only for a minor
      part of the total HHV8 ORF74 signaling. The activation pattern of ECRF3 with
      constitutive activation of some (but not all) of the employed pathways has not
      been seen before in endogenous or virus-encoded chemokine receptors. The results
      suggest that the unique ligand selectivity of ECRF3 among ORF74 receptors could
      reflect differences in the cellular tropism of the gamma(2)-herpesviruses.

PMID- 15155731
TI  - The metal-free and calcium-bound structures of a gamma-carboxyglutamic acid
      containing contryphan from Conus marmoreus, glacontryphan-M.
AB  - Glacontryphan-M, a novel calcium-dependent inhibitor of L-type voltage-gated
      Ca(2+) channels expressed in mouse pancreatic beta-cells, was recently isolated
      from the venom of the cone snail Conus marmoreus (Hansson, K., Ma, X., Eliasson,
      L., Czerwiec, E., Furie, B., Furie, B. C., Rorsman, P., and Stenflo, J. (2004) J.
      Biol. Chem. 278, 32453-32463). The conserved disulfide-bonded loop of the
      contryphan family of conotoxins including a D-Trp is present; however, unique to
      glacontryphan-M is a histidine within the intercysteine-loop and two gamma
      carboxyglutamic acid (Gla) residues, formed by post-translational modification of
      glutamic acid. The two calcium-binding Gla residues are located in a four residue
      N-terminal extension of this contryphan. To better understand the structural and
      functional significance of these residues, we have determined the structure of
      glacontryphan-M using two-dimensional (1)H NMR spectroscopy in the absence and
      presence of calcium. Comparisons of the glacontryphan-M structures reveal that
      calcium binding induces structural perturbations within the Gla-containing N
      terminus and the Cys(11)-Cys(5)-Pro(6) region of the intercysteine loop. The
      backbone of N-terminal residues perturbed by calcium, Gla(2) and Ser(3), moves
      away from the His(8) and Trp(10) aromatic rings and the alignment of the D-Trp(7)
      and His(8) aromatic rings with respect to the Trp(10) rings is altered. The
      blockage of L-type voltage-gated Ca(2+) channel currents by glacontryphan-M
      requires calcium binding to N-terminal Gla residues, where presumably histidine
      and tryptophan may be accessible for interaction with the channel. The backbone C
      alpha conformation of the intercysteine loop of calcium-bound glacontryphan-M
      superimposes on known structures of contryphan-R and Vn (0.83 and 0.66 A,
      respectively). Taken together these data identify that glacontryphan-M possesses
      the canonical contryphan intercysteine loop structure, yet possesses critical
      determinants necessary for a calcium-induced functionally required conformation.

PMID- 15155730
TI  - The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type
      calcium ion channel blocker isolated from the venom of Conus marmoreus.
AB  - Contryphans constitute a group of conopeptides that are known to contain an
      unusual density of post-translational modifications including tryptophan
      bromination, amidation of the C-terminal residue, leucine, and tryptophan
      isomerization, and proline hydroxylation. Here we report the identification and
      characterization of a new member of this family, glacontryphan-M from the venom
      of Conus marmoreus. This is the first known example of a contryphan peptide
      carrying glutamyl residues that have been post-translationally carboxylated to
      gamma-carboxyglutamyl (Gla) residues. The amino acid sequence of glacontryphan-M
      was determined using automated Edman degradation and electrospray ionization mass
      spectrometry. The amino acid sequence of the peptide is: Asn-Gla-Ser-Gla-Cys-Pro
      D-Trp-His-Pro-Trp-Cys. As with most other contryphans, glacontryphan-M is
      amidated at the C terminus and maintains the five-residue intercysteine loop. The
      occurrence of a D-tryptophan residue was confirmed by chemical synthesis and HPLC
      elution profiles. Using fluorescence spectroscopy we demonstrated that the Gla
      containing peptide binds calcium with a K(D) of 0.63 mM. Cloning of the full
      length cDNA encoding glacontryphan-M revealed that the primary translation
      product carries an N-terminal signal/propeptide sequence that is homologous to
      earlier reported contryphan signal/propeptide sequences up to 10 amino acids
      preceding the toxin region. Electrophysiological experiments, carried out on
      mouse pancreatic B-cells, showed that glacontryphan-M blocks L-type voltage-gated
      calcium ion channel activity in a calcium-dependent manner. Glacontryphan-M is
      the first contryphan reported to modulate the activity of L-type calcium ion
      channels.

PMID- 15155732
TI  - Neuregulin inhibits acetylcholine receptor aggregation in myotubes.
AB  - The high local concentration of acetylcholine receptors (AChRs) at the vertebrate
      neuromuscular junction results from their aggregation by the agrin/MuSK signaling
      pathway and their synthetic up-regulation by the neuregulin/ErbB pathway. Here,
      we show a novel role for the neuregulin/ErbB pathway, the inhibition of AChR
      aggregation on the muscle surface. Treatment of C2C12 myotubes with the
      neuregulin epidermal growth factor domain decreased the number of both
      spontaneous and agrin-induced AChR clusters, in part by increasing the rate of
      cluster disassembly. Upon cluster disassembly, AChRs were internalized into
      caveolae (as identified by caveolin-3). Time-lapse microscopy revealed that
      individual AChR clusters fragmented into puncta, and application of neuregulin
      accelerated the rate at which AChR clusters decreased in area without affecting
      the density of AChRs remaining in individual clusters (as measured by the
      fluorescence intensity/unit area). We propose that this novel action of
      neuregulin regulates synaptic competition at the developing neuromuscular
      junction.

PMID- 15155733
TI  - Mevalonate promotes the growth of tumors derived from human cancer cells in vivo
      and stimulates proliferation in vitro with enhanced cyclin-dependent kinase-2
      activity.
AB  - Malignant cells are known to have elevated rates of mevalonate synthesis because
      of increased levels and catalytic efficiency of 3-hydroxy-3-methylglutaryl-CoA
      reductase. Whether this increased mevalonate synthesis occurs as a consequence of
      increased requirements for a mevalonate-derived metabolite in response to rapid
      growth or whether mevalonate promotes the growth of tumor cells is unknown. To
      address this question, we administered mevalonate via miniosmotic pumps to nude
      mice inoculated with MDA-MB-435 human cancer cells. After 13 weeks of growth,
      tumors in mevalonate-treated mice were significantly larger than tumors in saline
      treated, control mice (1.52 +/- 0.26 g versus 0.81 +/- 0.27 g respectively, p <
      0.05). The cancer cells treated in culture with mevalonate also demonstrated
      increased proliferation rates associated with accelerated entry of cells into S
      phase. These cells had enhanced total and cyclin A-immunoprecipitable cyclin
      dependent kinase-2 (CDK-2) activity, increased activating phosphorylation of CDK
      2, and decreased inhibitory binding of CDK-2 to p21(Cip1). Our findings
      demonstrate that mevalonate promotes tumor growth and suggest that an increase in
      mevalonate synthesis in extrahepatic tissues following cholesterol-lowering
      therapy may explain the elevated risk of cancer shown in some studies.

PMID- 15155734
TI  - AcrA, AcrB, and TolC of Escherichia coli Form a Stable Intermembrane Multidrug
      Efflux Complex.
AB  - Many transporters of Gram-negative bacteria involved in the extracellular
      secretion of proteins and the efflux of toxic molecules operate by forming
      intermembrane complexes. These complexes are proposed to span both inner and
      outer membranes and create a bridge across the periplasm. In this study, we
      analyzed interactions between the inner and outer membrane components of the tri
      partite multidrug efflux pump AcrAB-TolC from Escherichia coli. We found that,
      once assembled, the intermembrane AcrAB-TolC complex is stable during the
      separation of the inner and outer membranes and subsequent purification. All
      three components of the complex co-purify when the affinity tag is attached to
      either of the proteins suggesting bi-partite interactions between AcrA, AcrB, and
      TolC. We show that antibiotics, the substrates of AcrAB-TolC, stabilize
      interactions within the complex. However, the formation of the AcrAB-TolC complex
      does not require an input of energy.

PMID- 15155735
TI  - Crystal structure of a Ca2+-discharged photoprotein: implications for mechanisms
      of the calcium trigger and bioluminescence.
AB  - Ca2+-regulated photoproteins are members of the EF-hand calcium-binding protein
      family. The addition of Ca2+ produces a blue bioluminescence by triggering a
      decarboxylation reaction of protein-bound hydroperoxycoelenterazine to form the
      product, coelenteramide, in an excited state. Based on the spatial structures of
      aequorin and several obelins, we have postulated mechanisms for the Ca2+ trigger
      and for generation of the different excited states that are the origin of the
      different colors of bioluminescence. Here we report the crystal structure of the
      Ca2+-discharged photoprotein obelin at 1.96-A resolution. The results lend
      support to the proposed mechanisms and provide new structural insight into
      details of these processes. Global conformational changes caused by Ca2+
      association are typical of the class of calcium signal modulators within the EF
      hand protein superfamily. Accommodation of the Ca2+ ions into the loops of the EF
      hands is seen to propagate into the active site of the protein now occupied by
      the coelenteramide where there is a significant repositioning and flipping of the
      His-175 imidazole ring as crucially required in the trigger hypothesis. Also the
      H-bonding between His-22 and the coelenterazine found in the active photoprotein
      is preserved at the equivalent position of coelenteramide, confirming the
      proposed rapid excited state proton transfer that would lead to the excited state
      of the phenolate ion pair, which is responsible for the blue emission of
      bioluminescence.

PMID- 15155736
TI  - Restoration of transforming growth factor-beta signaling through receptor RI
      induction by histone deacetylase activity inhibition in breast cancer cells.
AB  - The loss of transforming growth factor-beta (TGF-beta) response due to the
      dysregulation of TGF-beta receptors type I (RI) and type II (RII) is well known
      for its contribution to oncogenesis. Estrogen receptor-expressing breast cancer
      cells are refractory to TGF-beta-mediated growth control because of the reduced
      expression of TGF-beta receptors. Although RII is required for the binding of TGF
      beta to RI, RI is responsible for directly transducing TGF-beta signals through
      the Smad protein family. Treatment of estrogen receptor-expressing MCF-7L and
      ZR75 breast cancer cells with the histone deacetylase (HDAC) inhibitor
      suberoylanilide hydroxamic acid (SAHA) led to a dramatic induction of RI.
      Accumulation of acetylated histones H3 and H4 was observed in the SAHA-treated
      cells. Chromatin immunoprecipitation analysis followed by PCR with RI promoter
      specific primers indicated an accumulation of acetylated histones in chromatin
      associated with the RI gene, suggesting that histone deacetylation was involved
      in the transcriptional inactivation of RI. SAHA treatment stimulated RI promoter
      activity through the inhibition of Sp1/Sp3-associated HDAC activity. Histone
      acetyltransferase p300 stimulated RI promoter activity, thus further confirming
      the involvement of HDAC activity in the transcriptional repression of RI.
      Significantly, SAHA-mediated RI regeneration restored the TGF-beta response in
      breast cancer cells.

PMID- 15155737
TI  - An ATP-dependent activity that releases RanGDP from NTF2.
AB  - The small GTPase Ran functions in several critical processes in eukaryotic cells
      including nuclear transport, nuclear envelope formation, and spindle formation. A
      RanGDP-binding protein, NTF2, facilitates translocation of RanGDP through the
      nuclear pore complex and also acts to stabilize RanGDP against nucleotide
      exchange. Here, we identify a novel activity that stimulates release of GDP from
      Ran in the presence of NTF2. Hydrolyzable ATP enhances the GDP dissociation
      activity, and this enhancement is inhibited by nonhydrolyzable ATP analogues. In
      contrast, neither hydrolyzable ATP nor nonhydrolyzable ATP analogues affect GDP
      dissociation from Ran catalyzed by recombinant RCC1 or inhibition of GDP
      dissociation from Ran by recombinant NTF2. The ATP-dependent RanGDP dissociation
      activity therefore has the properties of a RanGDP dissociation inhibitor (GDI)
      displacement factor (RanGDF) where the GDI is NTF2. A protein phosphatase
      inhibitor mixture stimulates the RanGDF activity, suggesting the activity is
      regulated by phosphorylation. We propose that the ATP-dependent NTF2 releasing
      factor may have a role in the RanGDP/GTP cycle.

PMID- 15155738
TI  - Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell
      surface targeting.
AB  - Although homodimerization has been demonstrated for a large number of G protein
      coupled receptors (GPCRs), no general role has been attributed to this process.
      Because it is known that oligomerization plays a key role in the quality control
      and endoplasmic reticulum (ER) export of many proteins, we sought to determine if
      homodimerization could play such a role in GPCR biogenesis. Using the beta2
      adrenergic receptor (beta2AR) as a model, cell fractionation studies revealed
      that receptor homodimerization is an event occurring as early as the ER.
      Supporting the hypothesis that receptor homodimerization is involved in ER
      processing, beta2AR mutants lacking an ER-export motif or harboring a
      heterologous ER-retention signal dimerized with the wild-type receptor and
      inhibited its trafficking to the cell surface. Finally, in addition to inhibiting
      receptor dimerization, disruption of the putative dimerization motif,
      276GXXXGXXXL284, prevented normal trafficking of the receptor to the plasma
      membrane. Taken together, these data indicate that beta2AR homodimerization plays
      an important role in ER export and cell surface targeting.

PMID- 15155739
TI  - Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine
      regulation of kir channels by diverse modulators.
AB  - The activity of specific inwardly rectifying potassium (Kir) channels is
      regulated by any of a number of different modulators, such as protein kinase C,
      G(q) -coupled receptor stimulation, pH, intracellular Mg(2+) or the betagamma
      subunits of G proteins. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is an
      essential factor for maintenance of the activity of all Kir channels. Here, we
      demonstrate that the strength of channel-PIP(2) interactions determines the
      sensitivity of Kir channels to regulation by the various modulators. Furthermore,
      our results suggest that differences among Kir channels in their specific
      regulation by a given modulator may reflect differences in their apparent
      affinity of interactions with PIP(2).

PMID- 15155741
TI  - Discriminating scrapie and bovine spongiform encephalopathy isolates by infrared
      spectroscopy of pathological prion protein.
AB  - For the surveillance of transmissible spongiform encephalopathies (TSEs) in
      animals and humans, the discrimination of different TSE strains causing scrapie,
      BSE, or Creutzfeldt-Jakob disease constitutes a substantial challenge. We
      addressed this problem by Fourier transform-infrared (FT-IR) spectroscopy of
      pathological prion protein PrP27-30. Different isolates of hamster-adapted
      scrapie (263K, 22A-H, and ME7-H) and BSE (BSE-H) were passaged in Syrian
      hamsters. Two of these agents, 22A-H and ME7-H, caused TSEs with
      indistinguishable clinical symptoms, neuropathological changes, and
      electrophoretic mobilities and glycosylation patterns of PrP27-30. However, FT-IR
      spectroscopy revealed that PrP27-30 of all four isolates featured different
      characteristics in the secondary structure, allowing a clear distinction between
      the passaged TSE agents. FT-IR analysis showed that phenotypic information is
      mirrored in beta-sheet and other secondary structure elements of PrP27-30, also
      in cases where immunobiochemical typing failed to detect structural differences.
      If the findings of this study hold true for nonexperimental TSEs in animals and
      humans, FT-IR characterization of PrP27-30 may provide a versatile tool for
      molecular strain typing without antibodies and without restrictions to specific
      TSEs or mammalian species.

PMID- 15155740
TI  - Identification and characterization of the DNA-binding domain of the
      multifunctional PutA flavoenzyme.
AB  - The PutA flavoprotein from Escherichia coli is a transcriptional repressor and a
      bifunctional enzyme that regulates and catalyzes proline oxidation. PutA
      represses transcription of genes putA and putP by binding to the control DNA
      region of the put regulon. The objective of this study is to define and
      characterize the DNA binding domain of PutA. The DNA binding activity of PutA, a
      1320 amino acid polypeptide, has been localized to N-terminal residues 1-261.
      After exploring a potential DNA-binding region and an N-terminal deletion mutant
      of PutA, residues 1-90 (PutA90) were determined to contain DNA binding activity
      and stabilize the dimeric structure of PutA. Cell-based transcriptional assays
      demonstrate that PutA90 functions as a transcriptional repressor in vivo. The
      dissociation constant of PutA90 with the put control DNA was estimated to be 110
      nm, which is slightly higher than that of the PutA-DNA complex (K(d)
      approximately 45 nm). Primary and secondary structure analysis of PutA90
      suggested the presence of a ribbon-helix-helix DNA binding motif in residues 1
      47. To test this prediction, we purified and characterized PutA47. PutA47 is
      shown to purify as an apparent dimer, to exhibit in vivo transcriptional
      activity, and to bind specifically to the put control DNA. In gel-mobility shift
      assays, PutA47 was observed to bind cooperatively to the put control DNA with an
      overall dissociation constant of 15 nm for the PutA47-DNA complex. Thus, N
      terminal residues 1-47 are critical for DNA-binding and the dimeric structure of
      PutA. These results are consistent with the ribbon-helix-helix family of
      transcription factors.

PMID- 15155742
TI  - Differentiation induction of human keratinocytes by phosphatidylethanolamine
      binding protein.
AB  - Phosphatidylethanolamine-binding protein (PEBP) has been demonstrated to bind to
      Raf-1 and mitogen-activated protein kinase kinase, components of the
      extracellular signal-regulated protein kinase (ERK) pathway, thereby inhibiting
      the pathway and resulting in the suppression of cell proliferation. In the
      present study, we examined whether PEBP is involved in differentiation induction
      of human keratinocytes. PEBP expression was immunohistochemically examined in
      normal human skin and skin cancers with different differentiation properties.
      PEBP was not expressed in the basal layer of the epidermis but was expressed in
      the spinous and granular layers of normal skin. The protein was expressed in
      differentiated but not in undifferentiated carcinoma. PEBP expression was also
      examined in cultured normal human epidermal keratinocytes in which
      differentiation was induced by calcium treatment. Involucrin was used as a
      differentiation marker for spinous and granular cells. Northern blotting analysis
      indicated that both PEBP and involucrin mRNAs were enhanced 6 h after treatment
      with 2.0 mM CaCl(2). The protein amount of PEBP was also increased by this
      treatment. To investigate whether PEBP is involved in differentiation induction
      of keratinocytes, HaCaT keratinocytes were transfected with an expression vector.
      Fluorescent immunostain revealed that cells expressing PEBP exhibited enlarged
      and flattened cell shape, and induction of involucrin expression was demonstrated
      by immunoblot analysis. Although the protein amount of ERK was not altered,
      phosphorylated ERK levels were decreased and cell proliferation was partly
      inhibited by PEBP expression. These results indicate that PEBP not only inhibits
      cell proliferation but also induces differentiation of human keratinocytes.

PMID- 15155743
TI  - IkappaB kinase alpha and p65/RelA contribute to optimal epidermal growth factor
      induced c-fos gene expression independent of IkappaBalpha degradation.
AB  - Mitogenic activation of expression of immediate-early genes, such as c-fos, is
      controlled through signal-induced phosphorylation of constitutively bound
      transcription factors that is correlated with a nucleosomal response that
      involves inducible chromatin modifications, such as histone phosphorylation and
      acetylation. Here we have explored a potential role for the transcription factor
      NF-kappaB and its associated signaling components in mediating induction of c-fos
      gene expression downstream of epidermal growth factor (EGF)-dependent signaling.
      Here we show that EGF treatment of quiescent fibroblast does not induce the
      classical pathway of NF-kappaB activation through IkappaB kinase (IKK)-directed
      IkappaBalpha phosphorylation. Interestingly, efficient induction of c-fos
      transcription requires IKKalpha, one of the subunits of the IkappaB kinase
      complex. The NF-kappaB subunit, p65/RelA, is found constitutively associated with
      the c-fos promoter, and knock-out of this transcription factor significantly
      reduces c-fos gene expression. Importantly, EGF induces the recruitment of
      IKKalpha to the c-fos promoter to regulate promoter-specific histone H3 Ser(10)
      phosphorylation in a manner that is independent of p65/RelA. Collectively, our
      data demonstrate that IKKalpha and p65/RelA contribute significantly to EGF
      induced c-fos gene expression in a manner independent of the classical,
      IkappaBalpha degradation, p65/RelA nuclear accumulation response pathway.

PMID- 15155745
TI  - Knockdown of MTP18, a novel phosphatidylinositol 3-kinase-dependent protein,
      affects mitochondrial morphology and induces apoptosis.
AB  - We identified a novel human cDNA encoding a mitochondrial protein, MTP18
      (mitochondrial protein, 18 kDa) as a transcriptional downstream target of
      phosphatidylinositol (PI) 3-kinase signaling. We demonstrate that MTP18 mRNA as
      well as protein expression is dependent on PI 3-kinase activity. Confocal
      microscopy and biochemical fractionation revealed a mitochondrial localization of
      MTP18. Loss-of-function analysis employing antisense molecules revealed that
      MTP18 is essential for cell viability in PC-3 and HaCaT cells. We show that
      knockdown of MTP18 protein level results in a cytochrome c release from
      mitochondria and consequently leads to apoptosis. In addition, HaCaT cells with
      reduced levels of MTP18 become more sensitive to apoptotic stimuli. This effect
      is accompanied by dramatic subcellular alterations. Reduction of MTP18 impairs
      mitochondrial morphology resulting in the formation of a highly interconnected
      mitochondrial reticulum in COS-7 cells. Conversely, overexpression of MTP18
      induces a punctuate morphology of mitochondria suggesting also a functional role
      of MTP18 in maintaining the mitochondrial integrity. Hence, our data indicate an
      unexpected connection of PI 3-kinase signaling, apoptosis and the morphology of
      mammalian mitochondria.

PMID- 15155744
TI  - The herbicide paraquat induces dopaminergic nigral apoptosis through sustained
      activation of the JNK pathway.
AB  - Environmental exposure to the oxidant-producing herbicide paraquat has been
      implicated as a risk factor in Parkinson's disease. Although intraperitoneal
      paraquat injections in mice cause a selective loss of dopaminergic neurons in the
      substantia nigra pars compacta, the exact mechanism involved is still poorly
      understood. Our data show that paraquat induces the sequential phosphorylation of
      c-Jun N-terminal kinase (JNK) and c-Jun and the activation of caspase-3 and
      sequential neuronal death both in vitro and in vivo. These effects are diminished
      by the specific JNK inhibitor SP600125 and the antioxidant manganese(III)
      tetrakis (4-benzoic acid) porphyrin in vitro. Furthermore, JNK pathway inhibitor
      CEP-11004 effectively blocks paraquat-induced dopaminergic neuronal death in
      vivo. These results suggest that the JNK signaling cascade is a direct activator
      of the paraquat-mediated nigral dopaminergic neuronal apoptotic machinery and
      provides a molecular linkage between oxidative stress and neuronal apoptosis.

PMID- 15155747
TI  - Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death
      receptor transport to the cell surface in human colon cancer cells selected for
      resistance to TRAIL-induced apoptosis.
AB  - Many tumor cell types are sensitive to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis. Incubation of TRAIL-sensitive cells
      with TRAIL invariably leads to resistant survivors even when high doses of TRAIL
      are used. Because the emergence of resistance to apoptosis is a major concern in
      successful treatment of cancer, and TRAIL survivors may contribute to therapeutic
      failure, we investigated potential resistance mechanisms. We selected TRAIL
      resistant SW480 human colon adenocarcinoma cells by repeatedly treating them with
      high and/or low doses of TRAIL. The resulting TRAIL-resistant clones were not
      cross-resistant to Fas or paclitaxel. Expression of modulators of apoptosis was
      not changed in the resistant cells, including TRAIL receptors, cFLIP, Bax, Bid,
      or IAP proteins. Surprisingly, we found that DISC formation was deficient in
      multiple selected TRAIL-resistant clones. DR4 was not recruited to the DISC upon
      TRAIL treatment, and caspase-8 was not activated at the DISC. Although total
      cellular DR4 mRNA and protein were virtually identical in TRAIL-sensitive
      parental and TRAIL-resistant clones, DR4 protein expression on the cell surface
      was essentially undetectable in the TRAIL-resistant clones. Moreover, exogenous
      DR4 and KILLER/DR5 were not properly transported to the cell surface in the TRAIL
      resistant cells. Interestingly, TRAIL-resistant cells were resensitized to TRAIL
      by tunicamycin pretreatment, which increased cell surface expression of DR4 and
      KILLER/DR5. Our data suggest that tumor cells may become resistant to TRAIL
      through regulation of the death receptor cell surface transport and that
      resistance to TRAIL may be overcome by the glycosylation inhibitor/endoplasmic
      reticulum stress-inducing agent tunicamycin.

PMID- 15155746
TI  - Nuclear overexpression of NAD(P)H:quinone oxidoreductase 1 in Chinese hamster
      ovary cells increases the cytotoxicity of mitomycin C under aerobic and hypoxic
      conditions.
AB  - The effects of the subcellular localization of overexpressed bioreductive enzyme
      NAD(P)H:quinone oxidoreductase 1 (NQO1) on the activity of the antineoplastic
      agent mitomycin C (MC) under aerobic and hypoxic conditions were examined.
      Chinese hamster ovary (CHO-K1/dhfr(-)) cells were transfected with NQO1 cDNA to
      produce cells that overexpressed NQO1 activity in the nucleus (148-fold) or the
      cytosol (163-fold) over the constitutive level of the enzyme in parental cells.
      Subcellular localization of the enzyme was confirmed using antibody-assisted
      immunofluorescence. Nuclear localization of transfected NQO1 activity increased
      the cytotoxicity of MC over that produced by overexpression in the cytosol under
      both aerobic and hypoxic conditions, with greater cytotoxicity being produced
      under hypoxia. The greater cytotoxicity of nuclear localized NQO1 was not
      attributable to greater metabolic activation of MC but instead was the result of
      activation of the drug in close proximity to its target, nuclear DNA. A positive
      relationship existed between the degree of MC-induced cytotoxicity and the number
      of MC-DNA adducts produced. The findings indicate that activation of MC proximal
      to nuclear DNA by the nuclear localization of transfected NQO1 increases the
      cytotoxic effects of MC regardless of the degree of oxygenation and support the
      concept that the mechanism of action of MC involves alkylation of DNA.

PMID- 15155748
TI  - Semaphorin 3A stimulates neurite extension and regulates gene expression in PC12
      cells.
AB  - The secreted semaphorin 3A (Sema3A) is a member of a large family of proteins
      that act as guidance signals for axons and dendrites. While the receptors and
      signaling pathways that mediate the repulsive effects of semaphorins are
      beginning to be understood in some detail, the mechanisms that are responsible
      for the ability of Sema3A to stimulate the extension of dendrites remain to be
      elucidated. Here we show that PC12 cells, a model widely used to study neuronal
      differentiation, can be used to dissect this pathway. Sema3A is as effective as
      nerve growth factor in stimulating the extension of neurites from PC12 cells. We
      show that Sema3A is able to regulate gene expression and identify mitochondria as
      a novel target of Sema3A signaling. Pharmacological block of mitochondrial
      reactive oxygen species production abolishes the extension of neurites in
      response to Sema3A. These results show that the characterization of transcripts
      that are regulated by axon guidance signals may help to identify novel components
      of their signaling pathways.

PMID- 15155749
TI  - Genomic mechanisms of p210BCR-ABL signaling: induction of heat shock protein 70
      through the GATA response element confers resistance to paclitaxel-induced
      apoptosis.
AB  - Chronic myelogenous leukemia (CML) results from a t(9,22) translocation,
      producing the p210(BCR-ABL) oncoprotein, a tyrosine kinase that causes
      transformation and chemotherapy resistance. To further understand mechanisms
      mediating chemotherapy resistance, we identified 556 differentially regulated
      genes in HL-60 cells stably expressing p210(BCR-ABL) versus those expressing an
      empty vector using cDNA macro- and oligonucleotide microarrays. These BCR-ABL
      regulated gene products play diverse roles in cellular function including
      apoptosis, cell cycle regulation, intracellular signaling, transcription, and
      cellular adhesion. In particular, we identified up-regulation of the inducible
      form of heat shock protein 70 (Hsp70), and further explored the mechanism for its
      up-regulation. In HL-60/BCR-ABL and K562 cells (expressing p210(BCR-ABL)),
      abundant cytoplasmic Hsp70 expression was detected by immunoblot analysis.
      Moreover, cells isolated from bone marrow aspirates of patients in different
      stages of CML (chronic, aggressive, and blast crisis) express Hsp70. Expression
      of p210(BCR-ABL) in BCR-ABL negative cells induced transcription of the proximal
      Hsp70 promoter. Mutational analysis mapped the major p210(BCR-ABL) responsive
      element to a high affinity 5'(A/T)GATA(A/G)-3' "GATA" response element (GATA-RE)
      that binds GATA-1 in CML cells. The GATA-RE was sufficient to confer p210(BCR
      ABL)- and p185(BCR-ABL)-mediated trans-activation to an inert promoter. Short
      interfering RNA mediated "knockdown" of Hsp70 expression in K562 cells induced
      marked sensitivity to paclitaxel-induced apoptosis. Together these findings
      indicate that BCR-ABL confers chemotherapeutic resistance through intracellular
      signaling to the GATA-RE element found in the promoter region of the anti
      apoptotic Hsp70 protein. We suggest that down-regulation of the GATA-Hsp70
      pathway may be useful in the treatment of chemotherapy-resistant CML.

PMID- 15155750
TI  - Involvement of the L6-7 loop in SERCA1a Ca2+-ATPase activation by Ca2+ (or Sr2+)
      and ATP.
AB  - Wild-type (WT) and the double mutant D813A,D818A (ADA) of the L6-7 loop of
      SERCA1a were expressed in yeast, purified, and reconstituted into lipids. This
      allowed us to functionally study these ATPases by both kinetic and spectroscopic
      means, and to solve previous discrepancies in the published literature about both
      experimental facts and interpretation concerning the role of this loop in P-type
      ATPases. We show that in a solubilized state, the ADA mutant experiences a
      dramatic decrease of its calcium-dependent ATPase activity. On the contrary,
      reconstituted in a lipid environment, it displays an almost unaltered maximal
      calcium-dependent ATPase activity at high (millimolar) ATP, with an apparent
      affinity for Ca(2+) altered only moderately (3-fold). In the absence of ATP, the
      true affinity of ADA for Ca(2+) is, however, more significantly reduced (20-30
      fold) compared with WT, as judged from intrinsic (Trp) or extrinsic (fluorescence
      isothiocyanate) fluorescence experiments. At low ATP, transient kinetics
      experiments reveal an overshoot in the ADA phosphorylation level primarily
      arising from the slowing down of the transition between the nonphosphorylated
      "E2" and "Ca(2)E1" forms of ADA. At high ATP, this slowing down is only partially
      compensated for, as ADA turnover remains more sensitive to orthovanadate than WT
      turnover. ADA ATPase also proved to have a reduced affinity for ATP in studies
      performed under equilibrium conditions in the absence of Ca(2+), highlighting the
      long range interactions between L6-7 and the nucleotide-binding site. We propose
      that these mutations in L6-7 could affect protonation-dependent winding and
      unwinding events in the nearby M6 transmembrane segment.

PMID- 15155752
TI  - The Wilms tumor suppressor-1 target gene podocalyxin is transcriptionally
      repressed by p53.
AB  - Wilms tumors are a heterogeneous class of tumors in which Wilms tumor suppressor
      1 (WT1) and the p53 tumor suppressor may be variously inactivated by mutation,
      reduced in expression, or even overexpressed in the wild-type state. The
      downstream transcriptional targets of WT1 and p53 that are critical for mediating
      their roles in Wilms tumorigenesis are not well defined. The WiT49 cell line is
      characteristic of anaplastic Wilms tumors that are refractory to treatment and
      expresses wild-type WT1 and mutant p53. We have used the small molecule compound
      CP-31398 (Pfizer) to restore wild-type p53 function to the codon 248 mutant p53
      present in WiT49 cells. In these cells, CP-31398 activated transcription of p53
      regulated promoters and enhanced UV light-induced apoptosis without altering the
      overall p53 protein level. These phenotypes were accompanied by restored binding
      of the p53 protein to promoter sequences in vivo. Gene expression profiling of CP
      31398-treated WiT49 cells revealed subsets of putative p53 target genes that were
      up- or down-regulated. A preferred target of p53-mediated repression in this
      system is the podocalyxin (PODXL) gene. PODXL is also transcriptionally regulated
      by WT1 and has roles in cell adhesion and anti-adhesion. Our results show that
      PODXL is a bona fide target of p53-mediated transcriptional repression while
      being positively regulated by WT1. We propose that inappropriate expression of
      PODXL due to changes in WT1 and/or p53 activity may contribute to Wilms
      tumorigenesis.

PMID- 15155751
TI  - The structure of chondroitin B lyase complexed with glycosaminoglycan
      oligosaccharides unravels a calcium-dependent catalytic machinery.
AB  - Chondroitinase B from Pedobacter heparinus is the only known enzyme strictly
      specific for dermatan sulfate and is a widely used enzymatic tool for the
      structural characterization of glycosaminoglycans. This beta-helical
      polysaccharide lyase belongs to family PL-6 and cleaves the beta(1,4) linkage of
      dermatan sulfate in a random manner, yielding 4,5-unsaturated dermatan sulfate
      disaccharides as the product. The previously reported structure of its complex
      with a dermatan sulfate disaccharide product identified the -1 and -2 subsites of
      the catalytic groove. We present here the structure of chondroitinase B complexed
      with several dermatan sulfate and chondroitin sulfate oligosaccharides. In
      particular, the soaking of chondroitinase B crystals with a dermatan sulfate
      hexasaccharide results in a complex with two dermatan sulfate disaccharide
      reaction products, enabling the identification of the +2 and +1 subsites.
      Unexpectedly, this structure revealed the presence of a calcium ion coordinated
      by sequence-conserved acidic residues and by the carboxyl group of the l-iduronic
      acid at the +1 subsite. Kinetic and site-directed mutagenesis experiments have
      subsequently demonstrated that chondroitinase B absolutely requires calcium for
      its activity, indicating that the protein-Ca(2+)-oligosaccharide complex is
      functionally relevant. Modeling of an intact tetrasaccharide in the active site
      of chondroitinase B provided a better understanding of substrate specificity and
      the role of Ca(2+) in enzymatic activity. Given these results, we propose that
      the Ca(2+) ion neutralizes the carboxyl moiety of the l-iduronic acid at the
      cleavage site, whereas the conserved residues Lys-250 and Arg-271 act as Bronsted
      base and acid, respectively, in the lytic degradation of dermatan sulfate by
      chondroitinase B.

PMID- 15155753
TI  - Investigating the role of the little finger domain of Y-family DNA polymerases in
      low fidelity synthesis and translesion replication.
AB  - Dpo4 and Dbh are Y-family polymerases that originate from two closely related
      strains of Sulfolobaceae. Quite surprisingly, however, the two polymerases
      exhibit different enzymatic properties in vitro. For example, Dpo4 can replicate
      past a variety of DNA lesions, yet Dbh does so with a much lower efficiency. When
      replicating undamaged DNA, Dpo4 is prone to make base pair substitutions, whereas
      Dbh predominantly makes single-base deletions. Overall, the two proteins are 54%
      identical, but the greatest divergence is found in their respective little finger
      (LF) domains, which are only 41% identical. To investigate the role of the LF
      domain in the fidelity and lesion-bypassing abilities of Y-family polymerases, we
      have generated chimeras of Dpo4 and Dbh in which their LF domains have been
      interchanged. Interestingly, by replacing the LF domain of Dbh with that of Dpo4,
      the enzymatic properties of the chimeric enzyme are more Dpo4-like in that the
      enzyme is more processive, can bypass an abasic site and a thymine-thymine
      cyclobutane pyrimidine dimer, and predominantly makes base pair substitutions
      when replicating undamaged DNA. The converse is true for the Dpo4-LF-Dbh chimera,
      which is more Dbh-like in its processivity and ability to bypass DNA adducts and
      generate single-base deletion errors. Our studies indicate that the unique but
      variable LF domain of Y-family polymerases plays a major role in determining the
      enzymatic and biological properties of each individual Y-family member.

PMID- 15155754
TI  - Hypothalamic responses to long-chain fatty acids are nutritionally regulated.
AB  - Central administration of the long-chain fatty acid oleic acid inhibits food
      intake and glucose production in rats. Here we examined whether short term
      changes in nutrient availability can modulate these metabolic and behavioral
      effects of oleic acid. Rats were divided in three groups receiving a highly
      palatable energy-dense diet at increasing daily caloric levels (below, similar,
      or above the average of rats fed standard chow). Following 3 days on the assigned
      diet regimen, rats were tested for acute biological responses to the infusion of
      oleic acid in the third cerebral ventricle. Three days of overfeeding virtually
      obliterated the metabolic and anorectic effects of the central administration of
      oleic acid. Furthermore, the infusion of oleic acid in the third cerebral
      ventricle failed to decrease the expression of neuropeptide Y in the hypothalamus
      and of glucose-6-phosphatase in the liver following short term overfeeding. The
      lack of hypothalamic responses to oleic acid following short term overfeeding is
      likely to contribute to the rapid onset of weight gain and hepatic insulin
      resistance in this animal model.

PMID- 15155755
TI  - Paradoxical actions of endogenous and exogenous insulin-like growth factor
      binding protein-5 revealed by RNA interference analysis.
AB  - Insulin-like growth factor-binding protein-5 (IGFBP-5) is abundantly expressed in
      bone cells. To determine the physiological role(s) of endogenous IGFBP-5 in
      regulating bone cell growth, differentiation, and survival, we used short double
      stranded RNA (siRNA) to trigger RNA interference of IGFBP-5 in human osteosarcoma
      cells. The IGFBP-5 siRNA, targeting against a sequence unique to the IGFBP-5
      middle domain, efficiently reduced IGFBP-5 mRNA and protein levels. The IGFBP-5
      siRNA did not change the levels of IGFBP-4, a structurally related protein, or
      glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene. Knock-down of
      IGFBP-5 resulted in a significant increase in the number of transferase-mediated
      dUTP nick end labeling-positive cells and a decrease in a bone differentiation
      parameter (alkaline phosphatase activity) but had little effect on basal or
      insulin-like growth factor I-induced proliferation. Overexpression of a siRNA
      resistant IGFBP-5 mutant in the IGFBP-5 knock-down cells restored the levels of
      survival to the control level; overexpression of IGFBP-4 or wild type IGFBP-5 had
      no such effect. Paradoxically, the addition of exogenous IGFBP-5 not only failed
      to rescue IGFBP-5 knock-down-induced apoptosis, it caused a further increase in
      apoptosis. Furthermore, the addition of exogenous IGFBP-5 alone increased
      apoptosis. This pro-apoptotic action of exogenous IGFBP-5 was abolished when IGF
      I was added in excess, suggesting that exogenous IGFBP-5 increases apoptosis by
      binding to and inhibiting the activities of insulin-like growth factors. These
      results indicate that endogenous and exogenous IGFBP-5 exhibits opposing
      biological actions on cell survival and underscore the necessity and utility of
      studying IGFBP functions through loss-of-function approaches.

PMID- 15155756
TI  - Two distinct binding sites for high potential iron-sulfur protein and cytochrome
      c on the reaction center-bound cytochrome of Rubrivivax gelatinosus.
AB  - The photosynthetic cyclic electron transfer of the purple bacterium Rubrivivax
      gelatinosus, involving the cytochrome bc(1) complex and the reaction center, can
      be carried out via two pathways. A high potential iron-sulfur protein (HiPIP)
      acts as the in vivo periplasmic electron donor to the reaction center (RC)-bound
      cytochrome when cells are grown under anaerobic conditions in the light, while
      cytochrome c is the soluble electron carrier for cells grown under (8)aerobic
      conditions in the dark. A spontaneous reversion of R. gelatinosus C244, a
      defective mutant in synthesis of the RC-bound cytochrome by insertion of a Km(r)
      cassette leading to gene disruption with a slow growth rate, restores the normal
      photosynthetic growth. This revertant, designated C244-P1, lost the Km(r)
      cassette but synthesized a RC-bound cytochrome with an external 77-amino acid
      insertion derived from the cassette. We characterized the RC-bound cytochrome of
      this mutant by EPR, time-resolved optical spectroscopy, and structural analysis.
      We also investigated the in vivo electron transfer rates between the two soluble
      electron donors and this RC-bound cytochrome. Our results demonstrated that the
      C244-P1 RC-bound cytochrome is still able to receive electrons from HiPIP, but it
      is no longer reducible by cytochrome c(8). Combining these experimental and
      theoretical protein-protein docking results, we conclude that cytochrome c(8) and
      HiPIP bind the RC-bound cytochrome at two distinct but partially overlapping
      sites.

PMID- 15155757
TI  - Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase
      inhibitor, represses chromatin transcription and alters global gene expression.
AB  - Histone acetylation is a diagnostic feature of transcriptionally active genes.
      The proper recruitment and function of histone acetyltransferases (HATs) and
      deacetylases (HDACs) are key regulatory steps for gene expression and cell cycle.
      Functional defects of either of these enzymes may lead to several diseases,
      including cancer. HATs and HDACs thus are potential therapeutic targets. Here we
      report that garcinol, a polyisoprenylated benzophenone derivative from Garcinia
      indica fruit rind, is a potent inhibitor of histone acetyltransferases p300 (IC50
      approximately 7 microm) and PCAF (IC50 approximately 5 microm) both in vitro and
      in vivo. The kinetic analysis shows that it is a mixed type of inhibitor with an
      increased affinity for PCAF compared with p300. HAT activity-dependent chromatin
      transcription was strongly inhibited by garcinol, whereas transcription from DNA
      template was not affected. Furthermore, it was found to be a potent inducer of
      apoptosis, and it alters (predominantly down-regulates) the global gene
      expression in HeLa cells.

PMID- 15155758
TI  - Deletion of the intestinal peptide transporter affects insulin and TOR signaling
      in Caenorhabditis elegans.
AB  - The mammalian intestinal peptide transporter PEPT1 mediates the uptake of di- and
      tripeptides from the gut lumen into intestinal epithelial cells and acts in
      parallel with amino acid transporters. Here we address the importance of the
      PEPT1 orthologue PEP-2 for the assimilation of dietary protein and for overall
      protein nutrition in Caenorhabditis elegans. pep-2 is expressed specifically
      along the apical membrane of the intestinal cells, and in pep-2 deletion mutant
      animals, uptake of intact peptides from the gut lumen is abolished. The
      consequences are a severely retarded development, reduced progeny and body size,
      and increased stress tolerance. We show here that pep-2 cross-talks with both the
      C. elegans target of rapamycin (TOR) and the DAF-2/insulin-signaling pathways.
      The pep-2 mutant enhances the developmental and longevity phenotypes of daf-2,
      resulting, among other effects, in a pronounced increase in adult life span.
      Moreover, all aspects of a weak let-363/TOR RNA interference phenotype are
      intensified by pep-2 deletion, indicating that pep-2 function upstream of TOR
      mediated nutrient sensing. Our findings provide evidence for a predominant role
      of the intestinal peptide transporter for the delivery of bulk quantities of
      amino acids for growth and development, which consequently affects signaling
      pathways that regulate metabolism and aging.

PMID- 15155760
TI  - Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically
      detoxify peroxynitrite via oxidation of fast reacting thiols.
AB  - Macrophage activation is one of the hallmarks observed in trypanosomiasis, and
      the parasites must cope with the resulting oxidative burden, which includes the
      production of peroxynitrite, an unusual peroxo-acid that acts as a strong oxidant
      and trypanocidal molecule. Cytosolic tryparedoxin peroxidase (cTXNPx) has been
      recently identified as essential for oxidative defense in trypanosomatids. This
      peroxiredoxin decomposes peroxides using tryparedoxin (TXN) as electron donor,
      which in turn is reduced by dihydrotrypanothione. In this work, we studied the
      kinetics of the reaction of peroxynitrite with the different thiol-containing
      components of the cytosolic tryparedoxin peroxidase system in T. brucei (Tb) and
      T. cruzi (Tc), namely trypanothione, TXN, and cTXNPx. We found that whereas
      peroxynitrite reacted with dihydrotrypanothione and TbTXN at moderate rates (7200
      and 3500 m(-1) s(-1), respectively, at pH 7.4 and 37 degrees C) and within the
      range of typical thiols, the second order rate constants for the reaction of
      peroxynitrite with reduced TbcTXNPx and TccTXNPx were 9 x 10(5) and 7.2 x 10(5)
      m(-1) s(-1) at pH 7.4 and 37 degrees C, respectively. This reactivity was
      dependent on a highly reactive cTXNPx thiol group identified as cysteine 52.
      Competition experiments showed that TbcTXNPx inhibited other fast peroxynitrite
      mediated processes, such as the oxidation of Mn(3+)-porphyrins. Moreover, steady
      state kinetic studies indicate that peroxynitrite-dependent TbcTXNPx and TccTXNPx
      oxidation is readily reverted by TXN, supporting that these peroxiredoxins would
      be not only a preferential target for peroxynitrite reactivity but also be able
      to act catalytically in peroxynitrite decomposition in vivo.

PMID- 15155759
TI  - The role of hsp90 in heme-dependent activation of apo-neuronal nitric-oxide
      synthase.
AB  - Like other nitric-oxide synthase (NOS) enzymes, neuronal NOS (nNOS) turnover and
      activity are regulated by the ubiquitous protein chaperone hsp90. We have shown
      previously that nNOS expressed in Sf9 cells where endogenous heme levels are low
      is activated from the apo- to the holo-enzyme by addition of exogenous heme to
      the culture medium, and this activation is inhibited by radicicol, a specific
      inhibitor of hsp90 (Billecke, S. S., Bender, A. T., Kanelakis, K. C., Murphy, P.
      J. M., Lowe, E. R., Kamada, Y., Pratt, W. B., and Osawa, Y. (2002) J. Biol. Chem.
      278, 15465-15468). In this work, we examine heme binding by apo-nNOS to form the
      active enzyme in a cell-free system. We show that cytosol from Sf9 cells
      facilitates heme-dependent apo-nNOS activation by promoting functional heme
      insertion into the enzyme. Sf9 cytosol also converts the glucocorticoid receptor
      (GR) to a state where the hydrophobic ligand binding cleft is open to access by
      steroid. Both cell-free heme activation of purified nNOS and activation of
      steroid binding activity of the immunopurified GR are inhibited by radicicol
      treatment of Sf9 cells prior to cytosol preparation, and addition of purified
      hsp90 to cytosol partially overcomes this inhibition. Although there is an hsp90
      dependent machinery in Sf9 cytosol that facilitates heme binding by apo-nNOS, it
      is clearly different from the machinery that facilitates steroid binding by the
      GR. hsp90 regulation of apo-nNOS heme activation is very dynamic and requires
      higher concentrations of radicicol for its inhibition, whereas GR steroid binding
      is determined by assembly of stable GR.hsp90 heterocomplexes that are formed by a
      purified five-chaperone machinery that does not activate apo-nNOS.

PMID- 15155761
TI  - Escherichia coli L-serine deaminase requires a [4Fe-4S] cluster in catalysis.
AB  - L-Serine deaminases catalyze the deamination of L-serine, producing pyruvate and
      ammonia. Two families of these proteins have been described and are delineated by
      the cofactor that each employs in catalysis. These are the pyridoxal 5'-phosphate
      dependent deaminases and the deaminases that are activated in vitro by iron and
      dithiothreitol. In contrast to the enzymes that employ pyridoxal 5'-phosphate,
      detailed physical and mechanistic characterization of the iron-dependent
      deaminases is limited, primarily because of their extreme instability. We report
      here the characterization of L-serine deaminase from Escherichia coli, which is
      the product of the sdaA gene. When purified anaerobically, the isolated protein
      contains 1.86 +/- 0.46 eq of iron and 0.670 +/- 0.019 eq of sulfide per
      polypeptide and displays a UV-visible spectrum that is consistent with a [4Fe-4S]
      cluster. Reconstitution of the protein with iron and sulfide generates
      considerably more of the cluster, and treatment of the reconstituted protein with
      dithionite gives rise to an axial EPR spectrum, displaying g axially = 2.03 and g
      radially = 1.93. Mossbauer spectra of the (57)Fe-reconstituted protein reveal
      that the majority of the iron is in the form of [4Fe-4S](2+) clusters, as
      evidenced by the typical Mossbauer parameters-isomer shift, delta = 0.47 mm/s,
      quadrupole splitting of Delta E(Q) = 1.14 mm/s, and a diamagnetic (S = 0) ground
      state. Treatment of the dithionite-reduced protein with L-serine results in a
      slight broadening of the feature at g = 2.03 in the EPR spectrum of the protein,
      and a dramatic loss in signal intensity, suggesting that the amino acid interacts
      directly with the cluster.

PMID- 15155762
TI  - The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57
      protein interacts with REF protein and acts as an RNA export factor.
AB  - ORF57 (MTA) one of the earliest Kaposi's sarcoma-associated herpesvirus (KSHV)
      regulatory proteins to be expressed is essential for virus lytic replication. A
      counterpart is present in every herpesvirus sequenced, indicating the importance
      of this signature viral protein and those examined act post-transcriptionally,
      affecting RNA splicing and transport. In KSHV-infected cells, ORF57 protein was
      present in a complex with REF (Aly) and TAP (NXF1), factors involved in cellular
      mRNA export. The ORF57 N-terminal region interacts with REF, whereas both N- and
      C-terminal domains of REF interact with ORF57. The ORF57-REF interaction was
      direct, whereas TAP appeared to be recruited via REF. In somatic cells,
      ectopically expressed ORF57 protein was shown to function as a CRM1-independent
      nuclear mRNA export factor, promoting export of mRNAs that are poor substrates
      for splicing. The gamma-herpesvirus ORF57 protein, and its alpha-1 herpesvirus
      ICP27 counterpart both export RNA through pathways involving REF and TAP
      proteins, although divergence of these herpesvirus subfamilies occurred some 180
      210 million years ago. The TAP-mediated cellular mRNA export pathway is CRM1
      independent. However, human immunodeficiency virus type 1 Rev protein-mediated
      RNA export, which is CRM1-dependent, was considerably inhibited by ORF57,
      suggesting that Rev and ORF57 compete for a common export component. These data
      strengthen arguments that TAP and CRM1 pathways converge in accessing similar
      components of the nuclear pore complex. We propose that ORF57-mediated RNA export
      may use different export factors to accommodate the KSHV-infected host cell
      environments, for example, in B-cells or endothelial cells and during the
      different phases of lytic virus replication.

PMID- 15155763
TI  - Chromosomal and plasmid-encoded enzymes are required for assembly of the R3-type
      core oligosaccharide in the lipopolysaccharide of Escherichia coli O157:H7.
AB  - The type R3 core oligosaccharide predominates in the lipopolysaccharides from
      enterohemorrhagic Escherichia coli isolates including O157:H7. The R3 core
      biosynthesis (waa) genetic locus contains two genes, waaD and waaJ, that are
      predicted to encode glycosyltransferases involved in completion of the outer
      core. Through determination of the structures of the lipopolysaccharide core in
      precise mutants and biochemical analyses of enzyme activities, WaaJ was shown to
      be a UDP-glucose:(galactosyl) lipopolysaccharide alpha-1,2-glucosyltransferase,
      and WaaD was shown to be a UDP-glucose:(glucosyl)lipopolysaccharide alpha-1,2
      glucosyltransferase. The residue added by WaaJ was identified as the ligation
      site for O polysaccharide, and this was confirmed by determination of the
      structure of the linkage region in serotype O157 lipopolysaccharide. The initial
      O157 repeat unit begins with an N-acetylgalactosamine residue in a beta-anomeric
      configuration, whereas the biological repeat unit for O157 contains alpha-linked
      N-acetylgalactosamine residues. With the characterization of WaaJ and WaaD, the
      activities of all of the enzymes encoded by the R3 waa locus are either known or
      predicted from homology data with a high level of confidence. However, when core
      oligosaccharide structure is considered, the origin of an additional alpha-1,3
      linked N-acetylglucosamine residue in the outer core is unknown. The gene
      responsible for a nonstoichiometric alpha-1,7-linked N-acetylglucosamine
      substituent in the heptose (inner core) region was identified on the large
      virulence plasmids of E. coli O157 and Shigella flexneri serotype 2a. This is the
      first plasmid-encoded core oligosaccharide biosynthesis enzyme reported in E.
      coli.

PMID- 15155764
TI  - Mammalian antioxidant defenses are not inducible by H2O2.
AB  - As an approach to understanding how mammals regulate H(2)O(2) toxicity,
      intracellular concentration to prevent its we analyzed the genome-wide mRNA
      profile changes of human cells after treatment with a non-toxic H(2)O(2)
      concentration. We identified a large and essentially late H(2)O(2) response of
      induced and repressed genes that unexpectedly comprise few or no antioxidants but
      mostly apoptosis and cell cycle control activities. The requirement of the p53
      regulator for regulating about a third of this H(2)O(2) stimulon and the lack of
      an associated enhancement of total cellular H(2)O(2) scavenging activity further
      suggest that H(2)O(2) elicits a stress antiproliferative/repair response that
      does not increase antioxidant defenses. We conclude that mammalian antioxidant
      defenses are constitutive, a finding that contrasts with the oxidant-inducibility
      of such defenses in microorganisms. This finding might be important in
      understanding the role of H(2)O(2) as a key signaling molecule in mammals.

PMID- 15155765
TI  - Molecular approximation between a residue in the amino-terminal region of
      calcitonin and the third extracellular loop of the class B G protein-coupled
      calcitonin receptor.
AB  - The calcitonin receptor is a member of the class B family of G protein-coupled
      receptors, which contains numerous potentially important drug targets.
      Delineation of themes for agonist binding and activation of these receptors will
      facilitate the rational design of receptor-active drugs. We reported previously
      that a photolabile residue within the carboxyl-terminal half (residue 26) and mid
      region (residue 16) of calcitonin covalently label the extracellular amino
      terminal domain of this receptor (Dong, M., Pinon, D. I., Cox, R. F., and Miller,
      L. J. (2004) J. Biol. Chem. 279, 1167-1175). Chimeric receptor studies support
      the importance of this region and suggest important contributions of
      extracellular loop domains. To examine whether other parts of the ligand may
      contact those loops, we developed another probe that has its photolabile site of
      labeling within the amino-terminal half in position 8 of the ligand. This probe
      was a full agonist (EC(50) = 563 +/- 67 pm), stimulating cAMP accumulation in
      receptor-bearing human embryonic kidney 293 cells in a concentration-dependent
      manner. It bound specifically and saturably (K(i) = 14.3 +/- 1.9 nm) and was able
      to efficiently label the calcitonin receptor. By purification, specific cleavage,
      and sequencing of labeled wild-type and mutant calcitonin receptors, the site of
      attachment was identified as residue Leu(368) within the third extracellular loop
      of the receptor, a domain distinct from that labeled by previous probes. These
      data are consistent with a common ligand binding mechanism for receptors in this
      important family.

PMID- 15155766
TI  - Structure and assembly of the RNA binding domain of bluetongue virus non
      structural protein 2.
AB  - Bluetongue virus non-structural protein 2 belongs to a class of highly conserved
      proteins found in orbiviruses of the Reoviridae family. Non-structural protein 2
      forms large multimeric complexes and localizes to cytoplasmic inclusions in
      infected cells. It is able to bind single-stranded RNA non-specifically, and it
      has been suggested that the protein is involved in the selection and condensation
      of the Bluetongue virus RNA segments prior to genome encapsidation. We have
      determined the x-ray structure of the N-terminal domain (sufficient for the RNA
      binding ability of non-structural protein 2) to 2.4 A resolution using anomalous
      scattering methods. Crystals of this apparently insoluble domain were obtained by
      in situ proteolysis of a soluble construct. The asymmetric unit shows two
      monomers related by non-crystallographic symmetry, with each monomer folded as a
      beta sandwich with a unique topology. The crystal structure reveals extensive
      monomer-monomer interactions, which explain the ability of the protein to self
      assemble into large homomultimeric complexes. Of the entire surface area of the
      monomer, one-third is used to create the interfaces of the curved multimeric
      assembly observed in the x-ray structure. The structure reported here shows how
      the N-terminal domain would be able to bind single-stranded RNA non-specifically
      protecting the bound regions in a heterogeneous multimeric but not polymeric
      complex.

PMID- 15155767
TI  - Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced
      excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential
      role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF
      kappa B pathway.
AB  - We have previously shown that two tumor necrosis factor (TNF) receptors (TNFR)
      exhibit antagonistic functions during neurodegenerative processes in vivo with
      TNFR1 aggravating and TNFR2 reducing neuronal cell loss, respectively. To
      elucidate the neuroprotective signaling pathways of TNFR2, we investigated
      glutamate-induced excitotoxicity in primary cortical neurons. TNF-expressing
      neurons from TNF-transgenic mice were found to be strongly protected from
      glutamate-induced apoptosis. Neurons from wild type and TNFR1(-/-) mice
      prestimulated with TNF or agonistic TNFR2-specific antibodies were also resistant
      to excitotoxicity, whereas TNFR2(-/-) neurons died upon glutamate and/or TNF
      exposures. Both protein kinase B/Akt and nuclear factor-kappa B (NF-kappa B)
      activation were apparent upon TNF treatment. Both TNFR1 and TNFR2 induced the NF
      kappa B pathway, yet with distinguishable kinetics and upstream activating
      components, TNFR1 only induced transient NF-kappa B activation, whereas TNFR2
      facilitated long term phosphatidylinositol 3-kinase-dependent NF-kappa B
      activation strictly. Glutamate-induced triggering of the ionotropic N-methyl-D
      aspartate receptor was required for the enhanced and persistent
      phosphatidylinositol 3-kinase-dependent NF-kappa B activation by TNFR2,
      indicating a positive cooperation of TNF and neurotransmitter-induced signal
      pathways. TNFR2-induced persistent NF-kappa B activity was essential for neuronal
      survival. Thus, the duration of NF-kappa B activation is a critical determinant
      for sensitivity toward excitotoxic stress and is dependent on a differential
      upstream signal pathway usage of the two TNFRs.

PMID- 15155768
TI  - Analysis of the role of ubiquitin-interacting motifs in ubiquitin binding and
      ubiquitylation.
AB  - The ubiquitin-interacting motif (UIM) is a short peptide motif with the dual
      function of binding ubiquitin and promoting ubiquitylation. This motif is
      conserved throughout eukaryotes and is present in numerous proteins involved in a
      wide variety of cellular processes including endocytosis, protein trafficking,
      and signal transduction. We previously reported that the UIMs of epsin were both
      necessary and sufficient for its ubiquitylation. In this study, we found that
      many, but not all, UIM-containing proteins were ubiquitylated. When expressed as
      chimeric fusion proteins, most UIMs promoted ubiquitylation of the chimera. In
      contrast to previous studies, we found that UIMs do not exclusively promote
      monoubiquitylation but rather a mixture of mono-, multi-, and polyubiquitylation.
      However, UIM-dependent polyubiquitylation does not lead to degradation of the
      modified protein. UIMs also bind polyubiquitin chains of varying lengths and to
      different degrees, and this activity is required for UIM-dependent
      ubiquitylation. Mutational analysis of the UIM revealed specific amino acids that
      are important for both polyubiquitin binding and ubiquitin conjugation. Finally
      we provide evidence that UIM-dependent ubiquitylation inhibits the interaction of
      UIM-containing proteins with other ubiquitylated cellular proteins. Our results
      suggest a new model for the ubiquitylation of UIM-containing proteins.

PMID- 15155769
TI  - Redesign of carnitine acetyltransferase specificity by protein engineering.
AB  - In eukaryotes, L-carnitine is involved in energy metabolism by facilitating beta
      oxidation of fatty acids. Carnitine acetyltransferases (CrAT) catalyze the
      reversible conversion of acetyl-CoA and carnitine to acetylcarnitine and free
      CoA. To redesign the specificity of rat CrAT toward its substrates, we mutated
      Met564. The M564G mutated CrAT showed higher activity toward longer chain acyl
      CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild
      type CrAT, and lower activity toward its natural substrate, acetyl-CoA. Kinetic
      constants of the mutant CrAT showed modification in favor of longer acyl-CoAs as
      substrates. In the reverse case, mutation of the orthologous glycine (Gly553) to
      methionine in carnitine octanoyltransferase (COT) decreased activity toward its
      natural substrates, medium- and long-chain acyl-CoAs, and increased activity
      toward short-chain acyl-CoAs. Another CrAT mutant, M564A, was prepared and tested
      in the same way, with similar results. We conclude that Met564 blocks the entry
      of medium- and long-chain acyl-CoAs to the catalytic site of CrAT. Three
      dimensional models of wild-type and mutated CrAT and COT support this hypothesis.
      We show for the first time that a single amino acid is able to determine the
      substrate specificity of CrAT and COT.

PMID- 15155770
TI  - Species selectivity of nonpeptide antagonists of the gonadotropin-releasing
      hormone receptor is determined by residues in extracellular loops II and III and
      the amino terminus.
AB  - Efforts to develop orally available gonadotropin-releasing hormone (GnRH)
      receptor antagonists have led to the discovery of several classes of potent
      nonpeptide antagonists. Here we investigated molecular interactions of three
      classes of nonpeptide antagonists with human, rat, and macaque GnRH receptors.
      Although all are high affinity ligands of the human receptor (K(i) <5 nm), these
      compounds show reduced affinity for the macaque receptor and bind only weakly
      (K(i) >1 microm) to the rat receptor. To identify residues responsible for this
      selectivity, a series of chimeric receptors and mutant receptors was constructed
      and evaluated for nonpeptide binding. Surprisingly, 4 key residues located in the
      amino terminus (Met-24) and extracellular loops II (Ser-203, Gln-208) and III
      (Leu-300) of the GnRH receptor appear to be primarily responsible for species
      selective binding. Comparisons of reciprocal mutations suggest that these may not
      be direct contacts but rather may be involved in organizing extracellular
      portions of the receptor. These data are novel because most previous reports of
      residues involved in binding of nonpeptide ligands to peptide-activated G protein
      coupled receptors, including the GnRH receptor as well as mono-amine receptors,
      have identified binding sites in the transmembrane regions.

PMID- 15155771
TI  - Effect of omeprazole on gastric adenosine A1 and A2A receptor gene expression and
      function.
AB  - Adenosine has been shown to inhibit immunoreactive gastrin (IRG) release and to
      stimulate somatostatin-like immunoreactivity (SLI) release by activating
      adenosine A(1) and A(2A) receptors, respectively. Since the synthesis and release
      of gastrin and somatostatin are regulated by the acid secretory state of the
      stomach, the effect of achlorhydria on A(1) and A(2A) receptor gene expression
      and function was examined. Omeprazole-induced achlorhydria was shown to suppress
      A(1) and A(2A) receptor gene expression in the antrum and corporeal mucosa, but
      not in the corporeal muscle. Omeprazole treatment produced reciprocal changes in
      A(1) receptor and gastrin gene expression, and parallel changes in A(2A) receptor
      and somatostatin gene expression. The localization of A(1) and A(2A) receptors on
      gastrinsecreting G-cells and somatostatin-secreting D-cells, respectively,
      suggests that changes in adenosine receptor expression may modulate the synthesis
      and release of gastrin and somatostatin. Thus, the effect of omeprazole on
      adenosine receptor-mediated changes in IRG and SLI release was also examined in
      the vascularly perfused rat stomach. After omeprazole treatment, the A(1)
      receptor-mediated inhibition of IRG and SLI release induced by N(6)
      cyclopentyladenosine (A(1) receptor-selective agonist) was not altered, but the
      A(2A) receptor-mediated augmentation of SLI release induced by 2-p-(2
      carboxyethyl-)phenethylamino-5'-N-ethylcarboxamidoadenosine (A(2A)-selective
      agonist) was significantly attenuated. These findings agree well with the
      corresponding omeprazole-induced decrease in antral A(2A) receptor mRNA
      expression. Overall, the present study suggests that adenosine receptor gene
      expression and function may be altered by omeprazole treatment. Acid-dependent
      changes in adenosine receptor expression may represent a novel purinergic
      regulatory feedback mechanism in controlling gastric acid secretion.

PMID- 15155772
TI  - Immunologic basis for the rare occurrence of true nonsecretory plasma cell
      dyscrasias.
AB  - Lymphocytes and plasma cells are major actors of the adaptive immune response and
      can rightly be considered as human health keepers. However, recombination and
      mutation events occurring at high rate in the B cell lineage also expose these
      cells to gene alterations, potentially resulting in uncontrolled and life
      threatening cell proliferation. Although in cultured cell lines, such gene
      alterations frequently generate nonsecretory variants, most immunoproliferative B
      cell disorders feature in vivo immunoglobulin (Ig) secretion. In this paper, we
      review the molecular mechanisms involved in various instances of the rare,
      nonsecretory myelomas, in light of current notions about the molecular control of
      Ig production, assembly, and secretion in normal B cells. We finally document the
      attractive hypothesis that B cell clones, which retain nonsecretable,
      intracellular Igs, may be ideal, in vivo targets for efficient anti-idiotypic
      immune responses, and clones featuring an abundant secretion may by contrast
      easily induce T cell anergy and escape the anti-tumoral immune surveillance.

PMID- 15155773
TI  - Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are
      highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas
      with widespread nodular dissemination.
AB  - B cell neoplasms present heterogeneous patterns of lymphoid organ involvement,
      which may be a result of the differential expression of chemokine receptors. We
      found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5,
      the main chemokine receptors that mediate B cell entry into secondary lymphoid
      tissues and their homing to T cell and B cell zones therein, were highly
      expressed in B malignancies with widespread involvement of lymph nodes.
      Conversely, those pathologies with little or no nodular dissemination showed no
      expression to very low levels of CCR7 and CXCR5 and low to moderate levels of
      CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in
      determining the pattern of lymphoid organ involvement of B tumors. Functional
      studies were performed on B malignancies expressing different levels of CCR7,
      CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and
      did not migrate in response to their ligands; a moderate expression of CXCR4 on
      MM cells was accompanied by a migratory response to its ligand, CXCL12. By
      contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the
      highest levels of these chemokine receptors and efficiently migrated in response
      to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B
      CLL cells in response to both of the CCR7 ligands correlated with the presence of
      clinical lymphadenopathy, thus indicating that the high expression of functional
      chemokine receptors justifies the widespread character of B-CLL, representing a
      clinical target for the control of tumor cell dissemination.

PMID- 15155774
TI  - Bedside to bench and back again: how animal models are guiding the development of
      new immunotherapies for cancer.
AB  - Immunotherapy using adoptive cell transfer is a promising approach that can
      result in the regression of bulky, invasive cancer in some patients. However,
      currently available therapies remain less successful than desired. To study the
      mechanisms of action and possible improvements in cell-transfer therapies, we use
      a murine model system with analogous components to the treatment of patients. T
      cell receptor transgenic CD8+ T cells (pmel-1) specifically recognizing the
      melanocyte differentiation antigen gp100 are adoptively transferred into lympho
      depleted mice bearing large, established, 14-day subcutaneous B16 melanoma (0.5-1
      cm in diameter) on the day of treatment. Adoptive cell transfer in combination
      with interleukin interleukin-2 or interleukin-15 cytokine administration and
      vaccination using an altered form of the target antigen, gp100, can result in the
      complete and durable regression of large tumor burdens. Complete responders
      frequently develop autoimmunity with vitiligo at the former tumor site that often
      spreads to involve the whole coat. These findings have important implications for
      the design of immunotherapy trials in humans.

PMID- 15155775
TI  - Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine
      secretion, expression of cell adhesion molecules, and migration within 3-D
      collagen lattices.
AB  - Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein
      coupled receptors with seven-transmembrane domains. PAR2 can be activated by
      serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial
      proteases. This receptor is expressed by various cells and seems to be crucially
      involved during inflammation and the immune response. As previously reported,
      human neutrophils express functional PAR2. However, the precise physiological
      role of PAR2 on human neutrophils and its implication in human diseases remain
      unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show
      significantly enhanced migration in 3-D collagen lattices. PAR2 agonist
      stimulation also induced down-regulation of L-selectin display and up-regulation
      of membrane-activated complex-1 very late antigen-4 integrin expression on the
      neutrophil cell surface. Moreover, PAR2 stimulation results in an increased
      secretion of the cytokines interleukin (IL)-1beta, IL-8, and IL-6 by human
      neutrophils. These data indicate that PAR2 plays an important role in human
      neutrophil activation and may affect key neutrophil functions by regulating cell
      motility in the extracellular matrix, selectin shedding, and up-regulation of
      integrin expression and by stimulating the secretion of inflammatory mediators.
      Thus, PAR2 may represent a potential therapeutic target for the treatment of
      diseases involving activated neutrophils.

PMID- 15155776
TI  - CP-64131, an aminobenzazepine with cytokine-like properties, stimulates human
      neutrophil functions through the p38-MAPK pathway.
AB  - CP-64131 (CP), an aminobenzazepine with cytokine-like, physiologic effects
      similar to granulocyte-colony stimulating factor (G-CSF) and granulocyte
      macrophage (GM)-CSF, increases the number of neutrophils and stimulates marrow
      recovery after doxirubicin ablation. CP can also function as a neutrophil
      agonist, like formyl-Met-leu-Phe (fMLP). In these studies, we show that CP is
      unique in that it stimulates the p38-mitogen-activated protein kinase (MAPK)
      pathway but not extracellular signal-regulated kinase (ERK)1/2 or c-jun N
      terminal kinase MAPKs in human neutrophils from peripheral blood. This is in
      contrast to other neutrophil agonists such as fMLP, interleukin (IL)-8, or GM
      CSF, which stimulate multiple MAPK pathways. Like fMLP and IL-8, CP is capable of
      stimulating superoxide (O2-) production, CD11b expression, and cell polarization
      in human neutrophils. CP-stimulated O2- production is completely dependent on p38
      MAPK activation, as determined by sensitivity to the p38-MAPK inhibitor SB203580.
      In contrast, SB203580 only partially inhibits expression of CD11b and has no
      effect on cell polarization stimulated by CP. Therefore, CP treatment of
      neutrophils activates p38-MAPK but has effects independent of p38-MAPK
      activation. In human embryonic kidney 293 cells, a human kidney epithelial cell
      line CP stimulates p38-MAPK and modestly activates ERK1/2. The findings define CP
      as a novel, small molecule, which has little cellular toxicity in vitro. CP has
      the ability to activate specific MAPK pathways in different cell types and should
      prove to be an effective agonist in combination with inhibitors to study
      biological responses regulated by MAPKs.

PMID- 15155777
TI  - Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a
      role for CXCR2.
AB  - Leukocyte migration is critical to maintaining host defense, but uncontrolled
      cellular infiltration into tissues can lead to chronic inflammation. In the lung,
      such diseases include chronic obstructive pulmonary disease (COPD), a
      debilitating, respiratory condition characterized by progressive and largely
      irreversible airflow limitation for which cigarette smoking is the major risk
      factor. COPD is associated with an increased inflammatory cell influx including
      increased macrophage numbers in the airways and tissue. Alveolar macrophages
      develop from immigrating blood monocytes and have the capacity to cause the
      pathological changes associated with COPD. This study addressed the hypothesis
      that increased macrophage numbers in COPD are a result of increased recruitment
      of monocytes from the circulation. Chemotaxis assays of peripheral blood
      mononuclear cells (PBMC)/monocytes from nonsmokers, smokers, and COPD patients
      demonstrated increased chemotactic responses for cells from COPD patients when
      compared with controls toward growth-related oncogene (GRO)alpha and neutrophil
      activating peptide (NAP)-2 but not toward monocyte chemoattractant protein,
      interleukin-8, or epithelial-derived NAP(ENA)-78. The enhanced chemotactic
      response toward GROalpha and NAP-2 was not mediated by differences in expression
      of their cellular receptors, CXCR1 or CXCR2. Receptor expression studies using
      flow cytometry indicated that in COPD, monocyte expression of CXCR2 is regulated
      differently from nonsmokers and smokers, which may account for the enhanced
      migration toward GROalpha and NAP-2. The results highlight the potential of CXCR2
      antagonists as therapy for COPD and demonstrate that an enhanced PBMC/monocyte
      response to specific CXC chemokines in these patients may contribute to increased
      recruitment and activation of macrophages in the lungs.

PMID- 15155778
TI  - P-selectin inhibition suppresses muscle regeneration following injury.
AB  - This investigation sought to determine if P-selectin-mediated mechanisms
      contributed to macrophage localization in damaged muscle, an essential process
      for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P
      selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 microg/mouse or with
      100 microl vehicle alone, and then, lengthening contractions were induced in
      hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus
      muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury
      and substantial accumulation of CD11b+ mononuclear cells in the extracellular
      matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent
      decrease in the number of regenerating fibers (P=0.021), as determined by
      developmental myosin heavy chain (dMHC) expression. This expression was reduced
      93% at 7 days post-injury by the highest dose of sPSGL-1, which had no
      significant influence on intrafiber or extracellular accumulation of cells
      expressing CD11b, a general marker for phagocytic cells. Additional mice were
      injected i.v. with 20 microg anti-P-selectin or isotype-control immunoglobulin G
      and were then subjected to lengthening contractions as before. At 7 days post
      injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer
      mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages
      and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared
      with muscles from isotype-injected, control mice. The number of CD11b+ cells was
      not significantly different between groups. The results are consistent with the
      concept that P-selectin is involved in the recruitment, maturation, and/or
      activation of cells that are critical for muscle fiber regeneration.

PMID- 15155779
TI  - Decreased reactive oxygen species concentration in the elongation zone
      contributes to the reduction in maize leaf growth under salinity.
AB  - Reactive oxygen species (ROS) in the apoplast of cells in the growing zone of
      grass leaves are required for elongation growth. This work evaluates whether
      salinity-induced reductions in leaf elongation are related to altered ROS
      production. Studies were performed in actively growing segments (SEZ) obtained
      from leaf three of 14-d-old maize (Zea mays L.) seedlings gradually salinized to
      150 mM NaCl. Salinity reduced elongation rates and the length of the leaf growth
      zone. When SEZ obtained from the elongation zone of salinized plants (SEZs) were
      incubated in 100 mM NaCl, the concentration where growth inhibition was
      approximately 50%, O2*- production, measured as NBT formazan staining, was lower
      in these than in similar segments obtained from control plants. The NaCl effect
      was salt-specific, and not osmotic, as incubation in 200 mM sorbitol did not
      reduce formazan staining intensity. SEZs elongation rates were higher in 200 mM
      sorbitol than in 100 mM NaCl, but the difference could be cancelled by scavenging
      or inhibiting O2*- production with 10 mM MgCl2 or 200 microM diphenylene
      iodonium, respectively. The actual ROS believed to stimulate growth is *OH, a
      product of O2*- metabolism in the apoplast. SEZ(s) elongation in 100 mM NaCl was
      stimulated by a *OH-generating medium. Fusicoccin, an ATPase stimulant, and
      acetate buffer pH 4, could also enhance elongation in these segments, although
      both failed to increase ROS activity. These results show that decreased ROS
      production contributes to the salinity-associated reduction in grass leaf
      elongation, acting through a mechanism not associated with pH changes.

PMID- 15155780
TI  - A new technique for measurement of water permeability of stomatous cuticular
      membranes isolated from Hedera helix leaves.
AB  - Transpiration of cuticular membranes isolated from the lower stomatous surface of
      Hedera helix (ivy) leaves was measured using a novel approach which allowed a
      distinction to be made between gas phase diffusion (through stomatal pores) and
      solid phase diffusion (transport through the polymer matrix membrane and
      cuticular waxes) of water molecules. This approach is based on the principle that
      the diffusivity of water vapour in the gas phase can be manipulated by using
      different gases (helium, nitrogen, or carbon dioxide) while diffusivity of water
      in the solid phase is not affected. This approach allowed the flow of water
      across stomatal pores ('stomatal transpiration') to be calculated separately from
      the flow across the cuticle (cuticular transpiration) on the stomatous leaf
      surface. As expected, water flux across the cuticle isolated from the astomatous
      leaf surface was not affected by the gas composition since there are no gas
      filled pores. Resistance to flux of water through the solid cuticle on the
      stomatous leaf surface was about 11 times lower than cuticular resistance on the
      astomatous leaf surface, indicating pronounced differences in barrier properties
      between cuticles isolated from both leaf surfaces. In order to check whether this
      difference in resistance was due to different barrier properties of cuticular
      waxes on both leaf sides, mobility of 14C-labelled 2,4-dichlorophenoxy-butyric
      acid 14C-2,4-DB) in reconstituted cuticular wax isolated from both leaf surfaces
      was measured separately. However, mobility of 14C-2,4-DB in reconstituted wax
      isolated from the lower leaf surface was 2.6 times lower compared with the upper
      leaf side. The significantly higher permeability of the ivy cuticle on the lower
      stomatous leaf surface compared with the astomatous surface might result from
      lateral heterogeneity in permeability of the cuticle covering normal epidermal
      cells compared with the cuticle covering the stomatal cell surface.

PMID- 15155781
TI  - Molecular mapping of a gene responsible for Al-activated secretion of citrate in
      barley.
AB  - Aluminium (Al) toxicity is an important limitation to barley (Hordeum vulgare L.)
      on acid soil. Al-resistant cultivars of barley detoxify Al externally by
      secreting citrate from the roots. To link the genetics and physiology of Al
      resistance in barley, genes controlling Al resistance and Al-activated secretion
      of citrate were mapped. An analysis of Al-induced root growth inhibition from 100
      F2 seedlings derived from an Al-resistant cultivar (Murasakimochi) and an Al
      sensitive cultivar (Morex) showed that a gene associated with Al resistance is
      localized on chromosome 4H, tightly linked to microsatellite marker Bmag353.
      Quantitative trait locus (QTL) analysis from 59 F4 seedlings derived from an F3
      plant heterozygous at the region of Al resistance on chromosome 4H showed that a
      gene responsible for the Al-activated secretion of citrate was also tightly
      linked to microsatellite marker Bmag353. This QTL explained more than 50% of the
      phenotypic variation in citrate secretion in this population. These results
      indicate that the gene controlling Al resistance on barley chromosome 4H is
      identical to that for Al-activated secretion of citrate and that the secretion of
      citrate is one of the mechanisms of Al resistance in barley. The identification
      of the microsatellite marker associated with both Al resistance and citrate
      secretion provides a valuable tool for marker-assisted selection of Al-resistant
      lines.

PMID- 15155782
TI  - Transmembrane electron transport in sealed and NAD(P)H-loaded right-side-out
      plasma membrane vesicles isolated from maize (Zea mays L.) roots.
AB  - Electron transport across plasma membranes has been observed in vivo in several
      plant species and tissues after the application of ferricyanide (hexacyanoferrate
      III, HCF III). In the present work, a transmembrane electron flow was
      demonstrated in sealed and NAD(P)H-loaded right-side-out (apoplastic-side-out)
      plasma membrane vesicles isolated from maize (Zea mays L.) roots. HCF III was
      reduced at a rate of up to 126 nmol min(-1) mg(-1) protein by NADPH-loaded
      vesicles, while reduction rates with NADH-loaded vesicles were several-fold
      lower. Coincident with the reduction of HCF III, NAD(P)H oxidation was observed
      inside the vesicles. The dependence of reduction on K+ indicated an electrogenic
      transmembrane electron flow. Application of 100 microM calcium decreased HCF III
      reduction up to 66%, while pre-incubation with 200 microM warfarin or diphenylene
      iodonium inhibited transmembrane electron transport only weakly. Fe(3+)-EDTA was
      not reduced significantly by NADPH-loaded plasma membrane vesicles, whereas XTT
      was reduced at a rate of 765 pmol min(-1) mg(-1) protein. The results suggested a
      major function for NADPH in transmembrane electron flow and were discussed in
      conjunction with in vivo experiments.

PMID- 15155783
TI  - Ectopic expression of LLAG1, an AGAMOUS homologue from lily (Lilium longiflorum
      Thunb.) causes floral homeotic modifications in Arabidopsis.
AB  - The ABC model for floral development was proposed more than 10 years ago and
      since then many studies have been performed on model species, such as Arabidopsis
      thaliana, Antirrhinum majus, and many other species in order to confirm this
      hypothesis. This led to additional information on flower development and to more
      complex molecular models. AGAMOUS (AG) is the only C type gene in Arabidopsis and
      it is responsible for stamen and carpel development as well as floral
      determinacy. LLAG1, an AG homologue from lily (Lilium longiflorum Thunb.) was
      isolated by screening a cDNA library derived from developing floral buds. The
      deduced amino acid sequence revealed the MIKC structure and a high homology in
      the MADS-box among AG and other orthologues. Phylogenetic analysis indicated a
      close relationship between LLAG1 and AG orthologues from monocot species. Spatial
      expression data showed LLAG1 transcripts exclusively in stamens and carpels,
      constituting the C domain of the ABC model. Functional analysis was carried out
      in Arabidopsis by overexpression of LLAG1 driven by the CaMV35S promoter.
      Transformed plants showed homeotic changes in the two outer floral whorls with
      some plants presenting the second whorl completely converted into stamens.
      Altogether, these data strongly indicated the functional homology between LLAG1
      and AG.

PMID- 15155784
TI  - Convergence of interferon-gamma and progesterone signaling pathways in human
      endometrium: role of PIASy (protein inhibitor of activated signal transducer and
      activator of transcription-y).
AB  - All cardinal events during the reproductive cycle, including ovulation,
      implantation, and menstruation, are characterized by a profound tissue remodeling
      and an associated local inflammatory response. The ovarian hormone progesterone
      is a key modulator of inflammatory signals in reproductive tissues, but the
      underlying mechanisms are not well understood. In this study, we report that
      differentiating human endometrial stromal cells (ESCs) acquire resistance to
      interferon-gamma (IFNgamma)-dependent signal transducers and activators of
      transcription (STAT) 1 signaling, although phosphorylation, nuclear
      translocation, and binding of STAT1 to DNA, are unaffected. These observations
      prompted an investigation into the role of nuclear repressors of STAT1 signaling.
      We demonstrate that protein inhibitor of activated STAT-y is complexed to the
      progesterone receptor (PR) in human ESCs and that its ability to repress STAT1
      signaling is dependent upon activation of PR in response to hormone binding.
      Conversely, IFNgamma and protein inhibitor of activated STAT-y synergistically
      inhibited PR-dependent transcription, demonstrating that the progesterone and
      IFNgamma signaling pathways engage in reciprocal transcriptional antagonism in
      human endometrium.

PMID- 15155785
TI  - Transrepression of estrogen receptor beta signaling by nuclear factor-kappab in
      ovarian granulosa cells.
AB  - Estrogen receptor (ER) beta is the predominant ER in granulosa cells of the
      ovary. ERbeta is expressed at high levels in granulosa cell tumors (GCT) and in
      the human GCT-derived cell lines, COV434 and KGN. To gain insight into ERbeta
      function in granulosa cells and in GCT, we have used the COV434 and KGN cell
      lines. Although the cells bind estradiol (E2), transcriptional activation of a
      transfected estrogen-responsive reporter vector construct (ERE2-luc) by E2 was
      not observed. Transactivation was also not observed with cotransfected ERalpha or
      beta. This transcriptional resistance is specific to steroid receptor
      transactivation; reporter plasmids that are activated by the transcription
      factors activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB)
      demonstrate both constitutive and inducible transactivation. AP-1 and NF-kappaB
      are known to cause transrepression of both ERalpha- and glucocorticoid receptor
      mediated transcription. We therefore examined the possibility that activation of
      these pathways was responsible for the lack of a response to estrogen by using
      inhibitors of AP-1 or NF-kappaB. The AP-1 inhibitors alone had no effect, whereas
      inhibition of NF-kappaB signaling allowed a 3- to 4-fold E2-mediated induction of
      ERE2-luc. This response was both ligand and ER dependent. Repression of ERbeta
      signaling by NF-kappaB has not previously been reported. Recent evidence suggests
      that ERbeta may function to promote differentiation. The inhibition of ERbeta in
      combination with the antiapoptotic properties of NF-kappaB may therefore
      contribute to pathogenesis of GCT.

PMID- 15155786
TI  - The atypical orphan nuclear receptor DAX-1 interacts with orphan nuclear receptor
      Nur77 and represses its transactivation.
AB  - DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical
      region on the X chromosome, gene 1) (NROB1) is an atypical member of the nuclear
      receptor family, which lacks the classical zinc finger DNA binding domain and
      acts as a coregulator of a number of nuclear receptors. In this study, we have
      found that DAX-1 is a novel coregulator of the orphan nuclear receptor Nur77
      (NR4A1). We demonstrate that DAX-1 represses the Nur77 transactivation by
      transient transfection assays. Specific interaction between Nur77 and DAX-1 was
      detected by coimmunoprecipitation, yeast two-hybrid, and glutathione-S
      transferase pull-down assays. The ligand binding domain of DAX-1 and the
      activation function-2 domain of Nur77 were determined as the direct interaction
      domains between DAX-1 and Nur77. In vitro competition binding assay showed that
      DAX-1 repressed Nur77 transactivation through the competition with steroid
      receptor coactivator-1 for the binding of Nur77. Moreover, DAX-1 repressed Nur77-
      and LH-dependent increase of cytochrome P450 protein 17 promoter activity in
      transient transfection assays. Furthermore, Nur77-mediated transactivation was
      significantly increased by down-regulation of DAX-1 expression with DAX-1 small
      interfering RNA in testicular Leydig cell line, K28. LH treatment induced a
      transient increase in Nur77 mRNA, whereas LH repressed DAX-1 expression in a time
      and dose-dependent manner in K28 cells. In addition, immunohistochemical
      analysis showed the expression of Nur77 in mouse testicular Leydig cells. These
      results suggest that DAX-1 acts as a novel coregulator of the orphan nuclear
      receptor Nur77, and that the DAX-1 may play a key role in the regulation of Nur77
      mediated steroidogenesis in testicular Leydig cells.

PMID- 15155787
TI  - Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear
      factor 4alpha-deficient mice.
AB  - Hepatocyte nuclear factor (HNF) 4alpha is a liver-enriched nuclear receptor that
      plays a critical role in regulating the expression of numerous hepatic genes,
      including members of the cytochrome P450 (CYP) superfamily, several of which are
      expressed in a sex-dependent manner. Presently, we use a liver-specific Hnf4alpha
      deficient mouse model to investigate the role of HNF4alpha in regulating liver
      enriched transcription factors and sexually dimorphic Cyps in liver in vivo. Real
      time PCR analysis of RNA isolated from livers of wild-type and Hnf4alpha
      deficient mice revealed the following: 1) HNF4alpha exerts both positive
      regulation (Hnfalpha, C/ebpalpha, and C/ebpbeta) and negative regulation
      (Hnf3alpha and the HNF4alpha coactivator Pgc-1alpha) on liver transcription
      factor expression; 2) a strong dependence on HNF4alpha characterizes several male
      predominant Cyps (2d9 and 8b1), female-predominant Cyps (2b10, 2b13, 3a41, and
      3a44) and Cyps, whose expression is sex independent (3a11, 3a25); 3) HNF4alpha
      confers a unique, positive regulation of two male-expressed genes (Cyp4a12 and
      GSTpi) and a negative regulation of several female-predominant genes (Cyp2a4,
      Cyp2b9, Hnf3beta, and Hnf6), both of which are manifest in male but not female
      mouse liver. These trends were confirmed at the protein level by Western blot
      analysis using antibodies raised to Cyp2a, Cyp2b, and Cyp3a family members. Thus,
      HNF4alpha is an essential player in the complex regulatory network of liver
      enriched transcription factors and the sexually dimorphic mouse Cyp genes that
      they regulate. HNF4alpha is proposed to contribute to the sex specificity of
      liver gene expression by positively regulating a subset of male-specific Cyp
      genes while concomitantly inhibiting the expression of certain female-specific
      Cyps and liver transcription factors, by mechanisms that are operative in male,
      but not female, mouse liver.

PMID- 15155788
TI  - Burst generation in rat pyramidal neurones by regenerative potentials elicited in
      a restricted part of the basilar dendritic tree.
AB  - The common preconception about central nervous system neurones is that thousands
      of small postsynaptic potentials sum across the entire dendritic tree to generate
      substantial firing rates, previously observed in in vivo experiments. We present
      evidence that local inputs confined to a single basal dendrite can profoundly
      influence the neuronal output of layer V pyramidal neurones in the rat prefrontal
      cortical slices. In our experiments, brief glutamatergic stimulation delivered in
      a restricted part of the basilar dendritic tree invariably produced sustained
      plateau depolarizations of the cell body, accompanied by bursts of action
      potentials. Because of their small diameters, basolateral dendrites are not
      routinely accessible for glass electrode measurements, and very little is known
      about their electrical properties and their role in information processing.
      Voltage-sensitive dye recordings were used to follow membrane potential
      transients in distal segments of basal branches during sub- and suprathreshold
      glutamate and synaptic stimulations. Recordings were obtained simultaneously from
      multiple dendrites and multiple points along individual dendrites, thus showing
      in a direct way how regenerative potentials initiate at the postsynaptic site and
      propagate decrementally toward the cell body. The glutamate-evoked dendritic
      plateau depolarizations described here are likely to occur in conjunction with
      strong excitatory drive during so-called 'UP states', previously observed in in
      vivo recordings from mammalian cortices.

PMID- 15155789
TI  - Impaired regulation of neuronal nitric oxide synthase and heart rate during
      exercise in mice lacking one nNOS allele.
AB  - We tested the hypothesis that a single allele deletion of neuronal nitric oxide
      synthase (nNOS) would impair the neural control of heart rate following physical
      training, and that this phenotype could be restored following targeted gene
      transfer of nNOS. Voluntary wheel-running (+EX) in heterozygous nNOS knockout
      mice (nNOS(+/-), +EX; n= 52; peak performance 9.1 +/- 1.8 km day(-1)) was
      undertaken and compared to wild-type mice (n= 38; 9.5 +/- 0.8 km day(-1)). In
      anaesthetized wild-type mice, exercise increased phenylephrine-induced
      bradycardia by 67% (measured as heart rate change, in beats per minute, divided
      by the change in arterial blood pressure, in mmHg) or pulse interval response to
      phenylephrine by 52% (measured as interbeat interval change, in milliseconds,
      divided by the change in blood pressure). Heart rate changes or interbeat
      interval changes in response to right vagal nerve stimulation were also enhanced
      by exercise in wild-type atria (P < 0.05), whereas both in vivo and in vitro
      responses to exercise were absent in nNOS(+/-) mice. nNOS inhibition attenuated
      heart rate responses to vagal nerve stimulation in all atria (P < 0.05) and
      normalized the responses in wild-type, +EX with respect to wild-type with no
      exercise (-EX) atria. Atrial nNOS mRNA and protein were increased in wild-type,
      +EX compared to wild-type, -EX (P < 0.05), although exercise failed to have any
      effect in nNOS(+/-) atria. In vivo nNOS gene transfer using adenoviruses targeted
      to atrial ganglia enhanced choline acetyltransferase-nNOS co-localization (P <
      0.05) and increased phenylephrine-induced bradycardia in vivo and heart rate
      responses to vagal nerve stimulation in vitro compared to gene transfer of
      enhanced green fluorescent protein (eGFP, P < 0.01). This difference was
      abolished by nNOS inhibition (P < 0.05). In conclusion, genomic regulation of NO
      bioavailability from nNOS in cardiac autonomic ganglia in response to training is
      dependent on both alleles of the gene. Although basal expression of nNOS is
      normal, polymorphisms of nNOS may interfere with neural regulation of heart rate
      following training. Targeted gene transfer of nNOS can restore this impairment.

PMID- 15155790
TI  - Facilitating roles of murine platelet glycoprotein Ib and alphaIIbbeta3 in
      phosphatidylserine exposure during vWF-collagen-induced thrombus formation.
AB  - Vessel wall damage exposes collagen fibres, to which platelets adhere directly
      via the collagen receptors glycoprotein (GP) VI and integrin alpha(2)beta(1) and
      indirectly by collagen-bound von Willebrand factor (vWF) via the GPIb-V-IX and
      integrin alphaIIbbeta3 receptor complexes. Platelet-collagen interaction under
      shear stimulates thrombus formation in two ways, by integrin-dependent formation
      of platelet aggregates and by surface exposure of procoagulant phosphatidylserine
      (PS). GPVI is involved in both processes, complemented by alpha2beta1. In mouse
      blood flowing over collagen, we investigated the additional role of platelet-vWF
      binding via GPIb and alphaIIbbeta3. Inhibition of GPIb as well as blocking of vWF
      binding to collagen reduced stable platelet adhesion at high shear rate. This was
      accompanied by delayed platelet Ca(2+) responses and reduced PS exposure, while
      microaggregates were still formed. Inhibition of integrin alphaIIbbeta3 with
      JON/A antibody, which blocks alphaIIbbeta3 binding to both vWF and fibrinogen,
      reduced PS exposure and aggregate formation. The JON/A effects were not enhanced
      by combined blocking of GPIb-vWF binding, suggesting a function for alphaIIbbeta3
      downstream of GPIb. Typically, with blood from FcR gamma-chain +/- mutant mice,
      expressing 50% of normal platelet GPVI levels, GPIb blockage almost completely
      abolished platelet adhesion and PS exposure. Together, these data indicate that,
      under physiological conditions of flow, both adhesive receptors GPIb and
      alphaIIbbeta3 facilitate GPVI-mediated PS exposure by stabilizing platelet
      binding to collagen. Hence, these glycoproteins have an assistant procoagulant
      role in collagen-dependent thrombus formation, which is most prominent at reduced
      GPVI activity and is independent of the presence of thrombin.

PMID- 15155791
TI  - Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor
      activity in human skeletal muscle.
AB  - Despite increases in muscle sympathetic vasoconstrictor activity, skeletal muscle
      blood flow and O2 delivery increase during exercise in humans in proportion to
      the local metabolic demand, a phenomenon coupled to local reductions in the
      oxygenation state of haemoglobin and concomitant increases in circulating ATP. We
      tested the hypothesis that circulating ATP contributes to local blood flow and O2
      delivery regulation by both inducing vasodilatation and blunting the augmented
      sympathetic vasoconstrictor activity. In eight healthy subjects, we first
      measured leg blood flow (LBF) and mean arterial pressure (MAP) during three
      hyperaemic conditions: (1) intrafemoral artery adenosine infusion (vasodilator
      control), (2) intrafemoral artery ATP infusion (vasodilator), and (3) mild knee
      extensor exercise (approximately 20 W), and then compared the responses with the
      combined infusion of the vasoconstrictor drug tyramine, which evokes endogenous
      release of noradrenaline from sympathetic nerve endings. In all three hyperaemic
      conditions, LBF equally increased from approximately 0.5 +/- 0.1 l min(-1) at
      rest to approximately 3.6 +/- 0.3 l min(-1), with no change in MAP. Tyramine
      caused significant leg vasoconstriction during adenosine infusion (53 +/- 5 and
      56 +/- 5% lower LBF and leg vascular conductance, respectively, P < 0.05), which
      was completely abolished by both ATP infusion and exercise. In six additional
      subjects resting in the sitting position, intrafemoral artery infusion of ATP
      increased LBF and leg vascular conductance 27 +/- 3-fold, despite concomitant
      increases in venous noradrenaline and muscle sympathetic nerve activity of 2.5 +/
      0.2- and 2.4 +/- 0.1-fold, respectively. Maximal ATP-induced vasodilatation at
      rest accounted for 78% of the peak LBF during maximal bicycling exercise. Our
      findings in humans demonstrate that circulating ATP is capable of regulating
      local skeletal muscle blood flow and O2 delivery by causing substantial
      vasodilatation and negating the effects of increased sympathetic vasoconstrictor
      activity.

PMID- 15155792
TI  - Expression of heteromeric amino acid transporters along the murine intestine.
AB  - Members of the new heterodimeric amino acid transporter family are composed of
      two subunits, a catalytic multitransmembrane spanning protein (light chain) and a
      type II glycoprotein (heavy chain). These transporters function as exchangers and
      thereby extend the transmembrane amino acid transport selectivity to specific
      amino acids. The heavy chain rBAT associates with the light chain b degrees
      (,+)AT to form a cystine and cationic amino acid transporter. The other heavy
      chain, 4F2hc, can interact with seven different light chains to form various
      transporters corresponding to systems L, y(+)L, asc or x(-)(c). The importance of
      some of these transporters in intestinal and renal (re)absorption of amino acids
      is highlighted by the fact that mutations in either the rBAT or b degrees (,+)AT
      subunit result in cystinuria whereas a defect in the y(+)-LAT1 light chain causes
      lysinuric protein intolerance. Here we investigated the localization of these
      transporters in intestine since both diseases are also characterized by altered
      intestinal amino acid absorption. Real time PCR showed organ-specific expression
      patterns for all transporter subunit mRNAs along the intestine and Western
      blotting confirmed these findings on the protein level. Immunohistochemistry
      demonstrated basolateral coexpression of 4F2hc, LAT2 and y(+)-LAT1 in stomach and
      small intestine, whereas rBAT and b degrees (,+)AT were found colocalizing on the
      apical side of small intestine epithelium. In stomach, 4F2hc and LAT2 were
      localized in H(+)/K(+)-ATPase-expressing parietal cells. The abundant expression
      of several members of the heterodimeric transporter family along the murine small
      intestine suggests their involvement in amino acids absorption. Furthermore,
      strong expression of rBAT, b degrees (,+)AT and y(+)-LAT1 in the small intestine
      explains the reduced intestinal absorption of some amino acid in patients with
      cystinuria or lysinuric protein intolerance.

PMID- 15155793
TI  - Sequential activation of RhoA and FAK/paxillin leads to ATP release and actin
      reorganization in human endothelium.
AB  - We have investigated the cellular mechanisms of mechanical stress-induced
      immediate responses in human umbilical vein endothelial cells (HUVECs). Hypotonic
      stress (HTS) induced ATP release, which evoked a Ca(2+) transient, followed by
      actin reorganization within a few minutes, in HUVECs. Disruption of the actin
      cytoskeleton did not suppress HTS-induced ATP release, and inhibition of the ATP
      mediated Ca(2+) response did not affect actin reorganization, thereby indicating
      that these two responses are not interrelated. ATP release and actin
      reorganization were also induced by lysophosphatidic acid (LPA). HTS and LPA
      induced membrane translocation of RhoA, which occurs when RhoA is activated, and
      tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin. Tyrosine
      kinase inhibitors (herbimycin A or tyrphostin 46) inhibited both HTS- and LPA
      induced ATP release and actin reorganization, but did not affect RhoA activation.
      In contrast, Rho-kinase inhibitor (Y27632) inhibited all of the HTS- and LPA
      induced responses. These results indicate that the activation of the RhoA/Rho
      kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to
      ATP release and actin reorganization in HUVECs. Furthermore, the fact that HTS
      and LPA evoke exactly the same intracellular signals and responses suggests that
      even these immediate mechanosensitive responses are in fact not mechanical stress
      specific.

PMID- 15155795
TI  - Feeding the sleeping giant: muscle blood flow during whole body exercise.

PMID- 15155794
TI  - Mapping receptive fields in primary visual cortex.
AB  - Nearly 40 years ago, in the pages of this journal, Hubel and Wiesel provided the
      first description of receptive fields in the primary visual cortex of higher
      mammals. They defined two classes of cortical cells, "simple" and "complex",
      based on neural responses to simple visual stimuli. The notion of a hierarchy of
      receptive fields, where increasingly intricate receptive fields are constructed
      from more elementary ones, was introduced. Since those early days we have
      witnessed the birth of quantitative methods to map receptive fields and
      mathematical descriptions of simple and complex cell function. Insights gained
      from these models, along with new theoretical concepts, are refining our
      understanding of receptive field structure and the underlying cortical circuitry.
      Here, I provide a brief historical account of the evolution of receptive field
      mapping in visual cortex along with the associated conceptual advancements, and
      speculate on the shape novel theories of the cortex may take as a result these
      measurements.

PMID- 15155796
TI  - On inconsistency of the neighbor-joining, least squares, and minimum evolution
      estimation when substitution processes are incorrectly modeled.
AB  - Using analytical methods, we show that under a variety of model
      misspecifications, Neighbor-Joining, minimum evolution, and least squares
      estimation procedures are statistically inconsistent. Failure to correctly
      account for differing rates-across-sites processes, failure to correctly model
      rate matrix parameters, and failure to adjust for parallel rates-across-sites
      changes (a rates-across-subtrees process) are all shown to lead to a "long branch
      attraction" form of inconsistency. In addition, failure to account for rates
      across-sites processes is also shown to result in underestimation of evolutionary
      distances for a wide variety of substitution models, generalizing an earlier
      analytical result for the Jukes-Cantor model reported in Golding and a similar
      bias result for the GTR or REV model in Kelly and Rice (1996). Although standard
      rates-across-sites models can be employed in many of these cases to restore
      consistency, current models cannot account for other kinds of misspecification.
      We examine an idealized but biologically relevant case, where parallel changes in
      rates at sites across subtrees is shown to give rise to inconsistency. This
      changing rates-across-subtrees type model misspecification cannot be adjusted for
      with conventional methods or without carefully considering the rate variation in
      the larger tree. The results are presented for four-taxon trees, but the
      expectation is that they have implications for larger trees as well. To
      illustrate this, a simulated 42-taxon example is given in which the
      microsporidia, an enigmatic group of eukaryotes, are incorrectly placed at the
      archaebacteria-eukaryotes split because of incorrectly specified pairwise
      distances. The analytical nature of the results lend insight into the reasons
      that long branch attraction tends to be a common form of inconsistency and
      reasons that other forms of inconsistency like "long branches repel" can arise in
      some settings. In many of the cases of inconsistency presented, a particular
      incorrect topology is estimated with probability converging to one, the
      implication being that measures of uncertainty like bootstrap support will be
      unable to detect that there is a problem with the estimation. The focus is on
      distance methods, but previous simulation results suggest that the zones of
      inconsistency for distance methods contain the zones of inconsistency for maximum
      likelihood methods as well.

PMID- 15155797
TI  - A genome phylogeny for mitochondria among alpha-proteobacteria and a
      predominantly eubacterial ancestry of yeast nuclear genes.
AB  - Analyses of 55 individual and 31 concatenated protein data sets encoded in
      Reclinomonas americana and Marchantia polymorpha mitochondrial genomes revealed
      that current methods for constructing phylogenetic trees are insufficiently
      sensitive (or artifact-insensitive) to ascertain the sister of mitochondria among
      the current sample of eight alpha-proteobacterial genomes using mitochondrially
      encoded proteins. However, Rhodospirillum rubrum came as close to mitochondria as
      any alpha-proteobacterium investigated. This prompted a search for methods to
      directly compare eukaryotic genomes to their prokaryotic counterparts to
      investigate the origin of the mitochondrion and its host from the standpoint of
      nuclear genes. We examined pairwise amino acid sequence identity in comparisons
      of 6,214 nuclear protein-coding genes from Saccharomyces cerevisiae to 177,117
      proteins encoded in sequenced genomes from 45 eubacteria and 15 archaebacteria.
      The results reveal that approximately 75% of yeast genes having homologues among
      the present prokaryotic sample share greater amino acid sequence identity to
      eubacterial than to archaebacterial homologues. At high stringency comparisons,
      only the eubacterial component of the yeast genome is detectable. Our findings
      indicate that at the levels of overall amino acid sequence identity and gene
      content, yeast shares a sister-group relationship with eubacteria, not with
      archaebacteria, in contrast to the current phylogenetic paradigm based on
      ribosomal RNA. Among eubacteria and archaebacteria, proteobacterial and
      methanogen genomes, respectively, shared more similarity with the yeast genome
      than other prokaryotic genomes surveyed.

PMID- 15155798
TI  - Comparison of diverse protein sequences of the nuclear-encoded subunits of
      cytochrome C oxidase suggests conservation of structure underlies evolving
      functional sites.
AB  - Interspecific comparisons of protein sequences can reveal regions of evolutionary
      conservation that are under purifying selection because of functional
      constraints. Interpreting these constraints requires combining evolutionary
      information with structural, biochemical, and physiological data to understand
      the biological function of conserved regions. We take this integrative approach
      to investigate the evolution and function of the nuclear-encoded subunits of
      cytochrome c oxidase (COX). We find that the nuclear-encoded subunits evolved
      subsequent to the origin of mitochondria and the subunit composition of the
      holoenzyme varies across diverse taxa that include animals, yeasts, and plants.
      By mapping conserved amino acids onto the crystal structure of bovine COX, we
      show that conserved residues are structurally organized into functional domains.
      These domains correspond to some known functional sites as well as to other
      uncharacterized regions. We find that amino acids that are important for
      structural stability are conserved at frequencies higher than expected within
      each taxon, and groups of conserved residues cluster together at distances of
      less than 5 A more frequently than do randomly selected residues. We, therefore,
      suggest that selection is acting to maintain the structural foundation of COX
      across taxa, whereas active sites vary or coevolve within lineages.

PMID- 15155799
TI  - Early duplication and functional diversification of the opsin gene family in
      insects.
AB  - Recent analysis of the complete mosquito Anopheles gambiae genome has revealed a
      far higher number of opsin genes than for either the Drosophila melanogaster
      genome or any other known insect. In particular, the analysis revealed an
      extraordinary opsin gene content expansion, whereby half are long wavelength
      sensitive (LW) opsin gene duplicates. We analyzed this genomic data in
      relationship to other known insect opsins to estimate the relative timing of the
      LW opsin gene duplications and to identify "missing" paralogs in extant species.
      The inferred branching patterns of the LW opsin gene family phylogeny indicate at
      least one early gene duplication within insects before the emergence of the
      orders Orthoptera, Mantodea, Hymenoptera, Lepidoptera, and Diptera. These data
      predict the existence of one more LW opsin gene than is currently known from most
      insects. We tested this prediction by using a degenerate PCR strategy to screen
      the hymenopteran genome for novel LW opsin genes. We isolated two LW opsin gene
      sequences from each of five bee species, Bombus impatiens, B. terrestris,
      Diadasia afflicta, D. rinconis, and Osmia rufa, including 1.1 to 1.2 kb from a
      known (LW Rh1) and 1 kb from a new opsin gene (LW Rh2). Phylogenetic analysis
      suggests that the novel hymenopteran gene is orthologous to A. gambiae GPRop7, a
      gene that is apparently missing from D. melanogaster. Relative rate tests show
      that LW Rh2 is evolving at a slower rate than LW Rh1 and, therefore, may be a
      useful marker for higher-level hymenopteran systematics. Site-specific rate tests
      indicate the presence of several amino acid sites between LW Rh1 and LW Rh2 that
      have undergone shifts in selective constraints after duplication. These sites and
      others are discussed in relationship to putative structural and functional
      differences between the two genes.

PMID- 15155800
TI  - Within- and between-individual sequence variation among ITS1 copies in the meadow
      grasshopper Chorthippus parallelus indicates frequent intrachromosomal gene
      conversion.
AB  - Sequencing multiple copies of the ITS1 region revealed the coexistence of two or
      more haplotypes within the genome of Chorthippus parallelus. Using a PCR-RFLP
      approach, the ITS1 numbers and frequencies of haplotypes present in each of 40
      individuals were investigated, revealing a consistent lack of homogeneity. For
      each individual, the level of intra-individual variation was estimated from a
      sample of 20 ITS1 copies. The level of differentiation in haplotype frequency
      among individuals was then estimated by maximum likelihood using models based on
      the Dirichlet distribution. This confirmed the existence of significant levels of
      variation among individuals within each population studied. The most likely
      turnover mechanism that could generate this pattern of variation is gene
      conversion, operating at the intrachromosomal level. Furthermore, the discovery
      of linkage disequilibrium among the ITS1 haplotypes of C. parallelus suggests
      that intrachromosomal gene conversion occurs more frequently than
      interchromosomal recombination. Subspecies of C. parallelus showed significantly
      different haplotype distributions following about 0.5 Myr of divergence. With
      respect to the process of concerted evolution, we show that homogenization of
      repeats is slow relative to speciation, and the standing variation among
      individuals is sufficient for selection to operate.

PMID- 15155801
TI  - Differential selection of genes of cucumber mosaic virus subgroups.
AB  - Cucumber mosaic virus (CMV) has an extremely broad plant-host range, a large
      number of vector species, and a wide geographical distribution. CMV is,
      therefore, a model by which to understand plant virus adaptation. The selective
      constraints exerted on the five proteins expressed from the CMV genome were
      evaluated by application of newly developed maximum-likelihood algorithms to
      analyze sequences available in data banks. The ratio between nonsynonymous and
      synonymous substitution rates (omega) was used to detect positive selection on
      particular codon sites. Amino acid sequences were conserved with omega ranging
      from 0.07 to 0.60 in different proteins. However, a small proportion of amino
      acids in proteins 1a, 2a, and 3b, the coat protein (CP), were positively selected
      (omega > 1). Moreover, the evolution of the CP in the three subgroups of CMV
      strains revealed different selection profiles along the sequence and
      significantly different speed of evolution at many positions. Constraints exerted
      by aphid transmission, rather than plant adaptation, seemed to be responsible for
      these patterns of evolution in the CP.

PMID- 15155802
TI  - Origin and maintenance of a broad-spectrum disease resistance locus in
      Arabidopsis.
AB  - The broad-spectrum mildew resistance genes RPW8.1 and RPW8.2 define a unique type
      of plant disease resistance (R) gene, and so far homologous sequences have been
      found in Arabidopsis thaliana only, which suggests a recent origin. In addition
      to RPW8.1 and RPW8.2, the RPW8 locus contains three homologs of RPW8, HR1, HR2,
      and HR3, which do not contribute to powdery mildew resistance. To investigate
      whether RPW8 has originated recently, and if so the processes involved, we have
      isolated and analyzed the syntenic RPW8 loci from Arabidopsis lyrata, and from
      Brassica rapa and B. oleracea. The A. lyrata locus contains four genes
      orthologous to HR1, HR2, HR3, and RPW8.2, respectively. Two syntenic loci have
      been characterized in Brassica; one locus contains three genes and is present in
      both B. oleracea and B. rapa, and the other locus contains a single gene and is
      detected in B. rapa only. The Brassica homologs have highest similarity to HR3.
      Sequence analyses suggested that the RPW8 gene family in Brassicaceae originated
      from an HR3-like ancestor gene through a series of duplications and that RPW8.1
      and RPW8.2 evolved from functional diversification through positive selection
      several MYA. Examination of the sequence polymorphism of 32 A. thaliana
      accessions at the RPW8 locus and their disease reaction phenotypes revealed that
      the polymorphic RPW8 locus defines a major source of resistance to powdery mildew
      diseases. A possible evolutionary mechanism by which functional polymorphism at
      the AtRPW8 locus has been maintained in contemporary populations of A. thaliana
      is discussed.

PMID- 15155803
TI  - Tom22', an 8-kDa trans-site receptor in plants and protozoans, is a conserved
      feature of the TOM complex that appeared early in the evolution of eukaryotes.
AB  - One of the earliest events in the evolution of mitochondria was the development a
      means to translocate proteins made in the cytosol into the "protomitochondrion."
      How this was achieved remains uncertain, and the nature of the earliest version
      of the protein translocation machinery is not known. Comparative sequence
      analysis suggests three subunits, Tom40, Tom7, and Tom22 as common elements of
      the protein translocase in the mitochondrial outer membrane in diverse extant
      eukaryotes. Tom22, the 22-kDa subunit, plays a critical role in the function of
      this complex in fungi and animals, and we show that an 8-kDa subunit of the plant
      translocase is a truncated form of Tom22. It has a single transmembrane segment
      conforming in sequence to the same region of Tom22 from other eukaryotic lineages
      and a short carboxy-terminal trans domain located in the mitochondrial
      intermembrane space. The trans domain from the Arabidopsis thaliana protein
      functions in yeast lacking their own Tom22 by complementing protein import
      defects and restoring cell growth. Moreover, we have identified orthologs of
      Tom22, Tom7, and Tom40 in diverse eukaryotes such as the diatom Phaeodactylum
      tricornutum, the amoebic slime Dictyostelium discoideum, and the protozoan
      parasite Plasmodium falciparum. This finding strongly suggests these subunits as
      the core of the protein translocase in the earliest mitochondria.

PMID- 15155804
TI  - PV1 is a key structural component for the formation of the stomatal and fenestral
      diaphragms.
AB  - PV1 is an endothelial-specific integral membrane glycoprotein associated with the
      stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar
      organelles and the diaphragms of endothelial fenestrae. Multiple PV1 homodimers
      are found within each stomatal and fenestral diaphragm. We investigated the
      function of PV1 within these diaphragms and their regulation and found that
      treatment of endothelial cells in culture with phorbol myristate acetate (PMA)
      led to upregulation of PV1. This correlated with de novo formation of stomatal
      diaphragms of caveolae and transendothelial channels as well as fenestrae upon
      PMA treatment. The newly formed diaphragms could be labeled with anti-PV1
      antibodies. The upregulation of PV1 and formation of stomatal and fenestral
      diaphragms by PMA was endothelium specific and was the highest in microvascular
      endothelial cells compared with their large vessel counterparts. By using a siRNA
      approach, PV1 mRNA silencing prevented the de novo formation of the diaphragms of
      caveolae as well as fenestrae and transendothelial channels. Overexpression of
      PV1 in endothelial cells as well as in cell types that do not harbor caveolar
      diaphragms in situ induced de novo formation of caveolar stomatal diaphragms.
      Lastly, PV1 upregulation by PMA required the activation of Erk1/2 MAP kinase
      pathway and was protein kinase C independent. Taken together, these data show
      that PV1 is a key structural component, necessary for the biogenesis of the
      stomatal and fenestral diaphragms.

PMID- 15155805
TI  - MesA, a novel fungal protein required for the stabilization of polarity axes in
      Aspergillus nidulans.
AB  - The Aspergillus nidulans proteome possesses a single formin, SepA, which is
      required for actin ring formation at septation sites and also plays a role in
      polarized morphogenesis. Previous observations imply that complex regulatory
      mechanisms control the function of SepA and ensure its correct localization
      within hyphal tip cells. To characterize these mechanisms, we undertook a screen
      for mutations that enhance sepA defects. Of the mutants recovered, mesA1 causes
      the most dramatic defect in polarity establishment when SepA function is
      compromised. In a wild-type background, mesA1 mutants undergo aberrant hyphal
      morphogenesis, whereas septum formation remains unaffected. Molecular
      characterization revealed that MesA is a novel fungal protein that contains
      predicted transmembrane domains and localizes to hyphal tips. We show that MesA
      promotes the localized assembly of actin cables at polarization sites by
      facilitating the stable recruitment of SepA. We also provide evidence that MesA
      may regulate the formation or distribution of sterol-rich membrane domains. Our
      results suggest that these domains may be part of novel mechanism that directs
      SepA to hyphal tips.

PMID- 15155806
TI  - Localization of the blue-light receptor phototropin to the flagella of the green
      alga Chlamydomonas reinhardtii.
AB  - Blue light controls the sexual life cycle of Chlamydomonas, mediated by
      phototropin, a UV-A/blue-light receptor that plays a prominent role in multiple
      photoresponses. By using fractionation experiments and immunolocalization
      studies, this blue-light receptor, in addition to its known localization to the
      cell bodies, also was detected in flagella. Within the flagella, it was
      completely associated with the axonemes, in striking contrast to the situation in
      higher plants and the Chlamydomonas cell body where phototropin was observed in
      the plasma membrane. Its localization was not perturbed in mutants lacking
      several prominent structural components of the axoneme. This led to the
      conclusion that phototropin may be associated with the outer doublet
      microtubules. Analysis of a mutant (fla10) in which intraflagellar transport is
      compromised suggested that phototropin is a cargo for intraflagellar transport.
      The blue-light receptor thus seems to be an integral constituent of the flagella
      of this green alga, extending the list of organisms that harbor sensory molecules
      within this organelle to unicellular algae.

PMID- 15155807
TI  - The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a
      role in endocytic recycling.
AB  - The adaptor protein Numb is necessary for the cell fate specification of
      progenitor cells in the Drosophila nervous system. Numb is evolutionarily
      conserved and previous studies have provided evidence for a similar functional
      role during mammalian development. The Numb protein has multiple protein-protein
      interaction regions including a phosphotyrosine binding (PTB) domain and a
      carboxy-terminal domain that contains conserved interaction motifs including an
      EH (Eps15 Homology) domain binding motif and alpha-adaptin binding site. In this
      study we identify the EHD/Rme-1/Pincher family of endocytic proteins as Numb
      interacting partners in mammals and Drosophila. The EHD/Rme-1 proteins function
      in recycling of plasma membrane receptors internalized by both clathrin-mediated
      endocytosis and a clathrin-independent pathway regulated by ADP ribosylation
      factor 6 (Arf6). Here we report that Numb colocalizes with endogenous
      EHD4/Pincher and Arf6 and that Arf6 mutants alter Numb subcellular localization.
      In addition, we present evidence that Numb has a novel function in endosomal
      recycling and intracellular trafficking of receptors.

PMID- 15155808
TI  - Enteropathogenic Escherichia coli use redundant tyrosine kinases to form actin
      pedestals.
AB  - Enteropathogenic Escherichia coli (EPEC) are deadly contaminants in water and
      food and induce protrusion of actin-rich membrane pedestals beneath themselves
      upon attachment to intestinal epithelia. EPEC then causes intestinal
      inflammation, diarrhea, and, among children, death. Here, we show that EPEC uses
      multiple tyrosine kinases for formation of pedestals, each of which is sufficient
      but not necessary. In particular, we show that Abl and Arg, members of the Abl
      family of tyrosine kinases, localize and are activated in pedestals. We also show
      that pyrido[2,3-d]pyrimidine (PD) compounds, which inhibit Abl, Arg, and related
      kinases, block pedestal formation. Finally, we show that Abl and Arg are
      sufficient for pedestal formation in the absence of other tyrosine kinase
      activity, but they are not necessary. Our results suggest that additional kinases
      that are sensitive to inhibition by PD also can suffice. Together, these results
      suggest that EPEC has evolved a mechanism to use any of several functionally
      redundant tyrosine kinases during pathogenesis, perhaps facilitating its capacity
      to infect different cell types. Moreover, PD compounds are being developed to
      treat cancers caused by dysregulated Abl. Our results raise the possibility that
      PD may be useful in treating EPEC infections, and because PD affects host and not
      bacterium, selecting resistant strains may be far less likely than with
      conventional antibiotics.

PMID- 15155809
TI  - Atg21 is a phosphoinositide binding protein required for efficient lipidation and
      localization of Atg8 during uptake of aminopeptidase I by selective autophagy.
AB  - Delivery of proteins and organelles to the vacuole by autophagy and the cytoplasm
      to vacuole targeting (Cvt) pathway involves novel rearrangements of membrane
      resulting in the formation of vesicles that fuse with the vacuole. The mechanism
      of vesicle formation and the origin of the membrane are complex issues still to
      be resolved. Atg18 and Atg21 are proteins essential to vesicle formation and
      together with Ygr223c form a novel family of phosphoinositide binding proteins
      that are associated with the vacuole and perivacuolar structures. Their
      localization requires the activity of Vps34, suggesting that
      phosphatidylinositol(3)phosphate may be essential for their function. The
      activity of Atg18 is vital for all forms of autophagy, whereas Atg21 is required
      for the Cvt pathway but not for nitrogen starvation-induced autophagy. The loss
      of Atg21 results in the absence of Atg8 from the pre-autophagosomal structure
      (PAS), which may be ascribed to a reduced rate of conjugation of Atg8 to
      phosphatidylethanolamine. A similar defect in localization of a second ubiquitin
      like conjugate, Atg12-Atg5, suggests that Atg21 may be involved in the
      recruitment of membrane to the PAS.

PMID- 15155816
TI  - Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but
      not granulosa cells from polycystic ovaries.
AB  - The elevated insulin concentrations that occur in many women with polycystic
      ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism.
      The objective of the present study was to compare the content of proximal insulin
      signalling molecules in theca and granulosa cells between polycystic ovaries and
      regular cycling controls. Individual follicles (3-7 mm) were obtained from 11
      women with PCOS and 10 regularly cycling control women. The theca and granulosa
      cells were microdissected from each follicle. Total protein was extracted and
      signalling proteins were measured by western blot analysis. There was no
      difference in insulin receptor content between PCOS and controls in either theca
      or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased
      (P<0.05), but IRS-4 was decreased (P<0.03) in PCOS theca cells. There were no
      changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all
      samples. There were no changes in phosphatidyl inositol-3 kinase catalytic
      subunits p110alpha or p110beta in either theca or granulosa cells. These data
      demonstrate cell-specific alterations in IRS protein concentrations in theca
      cells from polycystic ovaries that are consistent with an exaggerated
      amplification of the insulin signal and which may play an important role in
      ovarian hyperandrogenism and thecal hyperplasia.

PMID- 15155810
TI  - The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for
      synaptic vesicle transport in Caenorhabditis elegans.
AB  - UNC-104 (KIF1A) is a kinesin motor that transports synaptic vesicles from the
      neuronal cell body to the terminal. Previous in vitro studies have shown that a
      Dictyostelium relative of UNC-104 transports liposomes containing acidic
      phospholipids, but whether this interaction is needed for the recognition and
      transport of synaptic vesicles in metazoans remains unexplored. Here, we have
      introduced mutations in the nonmotor domain of UNC-104 and examined whether these
      mutant motors can rescue an unc-104 Caenorhabditis elegans strain. We show that a
      pleckstrin homology (PH) domain in UNC-104 is essential for membrane transport in
      living C. elegans, that this PH domain binds specifically to phosphatidylinositol
      4,5-bisphosphate (PI(4,5)P(2)), and that point mutants in the PH domain that
      interfere with PI(4,5)P(2) binding in vitro also interfere with UNC-104 function
      in vivo. Several other lipid-binding modules could not effectively substitute for
      the UNC-104 PH domain in this in vivo assay. Real time imaging also revealed that
      a lipid-binding point mutation in the PH domain reduced movement velocity and
      processivity of individual UNC-104::GFP punctae in neurites. These results reveal
      a critical role for PI(4,5)P(2) binding in UNC-104-mediated axonal transport and
      shows that the cargo-binding properties of the distal PH domain can affect motor
      output.

PMID- 15155817
TI  - Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim
      NK cell ratio of the endometrium during the window of implantation.
AB  - The effects of hormone stimulation for IVF treatment on endometrial receptivity
      remain controversial. Since CD56(bright) natural killer (NK) cells in the
      endometrium positively contribute to implantation and decidualization whereas
      CD56(dim) NK cells are negatively associated with reproduction, shifts in the
      balance between those cells will affect receptivity. Therefore, we compared the
      leukocyte composition in the endometrium of IVF women (n=20) with non-pregnant
      women (n=18) in a natural cycle, as a parameter for endometrial quality. Biopsies
      were obtained 7 days after ovulation. Histological dating of the endometrium
      showed no increased endometrial advancement after IVF treatment as compared to
      the control group. Flow cytometric analysis of leukocyte subsets showed that
      hormonal stimulation positively affected the CD56(bright)/CD56(dim) ratio in the
      endometrium by a relative decrease in the cytotoxic CD56(dim)CD16(+) NK cell
      numbers. The relative number of T-cells remained unaffected, while the number of
      non-T and non-NK cells (i.e. B-cells and macrophages) was higher in the IVF
      group. These effects were restricted to the endometrium and not observed in
      peripheral blood. Within the CD56(bright) population we could identify a distinct
      subset of NK cells (CD56(superbright)) that was unique for the endometrium. We
      conclude that hormonal stimulation for IVF treatment positively affects the
      CD56(bright)/CD56(dim) ratio of the endometrium during the window of implantation
      and does not affect endometrial advancement.

PMID- 15155818
TI  - Two new novel point mutations localized upstream and downstream of the HMG box
      region of the SRY gene in three Indian 46,XY females with sex reversal and
      gonadal tumour formation.
AB  - The Y chromosome-specific gene SRY is one of the key genes involved in human sex
      determination. The SRY gene encodes a testis-specific transcription factor that
      plays a key role in sexual differentiation and development in males and is
      located on the distal region of the short arm of the Y chromosome. Mutations in
      SRY gene result in XY sex reversal and pure gonadal dysgenesis. SRY expression
      initiates a network of gene activity that transforms the undifferentiated gonad,
      genital ridge into testis. Mutations in the SRY gene have been considered to
      account for only 10-15% of 46,XY gonadal dysgenesis cases, whereas the majority
      of the remaining cases may have mutation(s) in the SRY regulatory elements or
      other genes involved in the sex differentiation pathway. Patients both with
      gonadal dysgenesis and Y-chromosome presence are at high risk of developing
      gonadoblastoma. Using PCR, single strand conformational polymorphism (SSCP) and
      automated DNA sequencing, we analysed the mutations in the SRY gene in three
      46,XY sex reversal patients. Two patients demonstrated nucleotide substitution (A
      ->G) within the open reading frame just outside and upstream of the conserved DNA
      binding motif called the high-mobility group (HMG) box, replacing glutamine at
      codon 57 with arginine. Altered SSCP patterns were also observed in these
      patients. Histological examination of gonads in patient 1 revealed the formation
      of gonadoblastoma. Patient 3 demonstrated A-->T substitution which replaces
      serine at codon 143 with cysteine, just outside but downstream of the HMG box.
      Results suggest the involvement of SRY gene in sex reversal which further
      supports the relationship between SRY alterations, gonadal dysgenesis and/or
      primary infertility.

PMID- 15155819
TI  - Roles of endogenous nitric oxide synthase inhibitors and endothelin-1 for
      regulating myometrial contractions during gestation in the rat.
AB  - This study investigated the roles of endogenous nitric oxide synthase (NOS)
      inhibitors and endothelin-1 (ET-1) for regulating myometrial contractions during
      gestation in the rat. Basal and stimulated cyclic GMP production with L-arginine
      as a NOS substrate or sodium nitroprusside (SNP) as a NO donor were significantly
      enhanced at the middle of gestation (14th day), while these were greatly
      decreased at term (22nd day), suggesting the accelerated NO production and/or up
      regulation of guanylate cyclase at the middle of gestation. NOS within the
      myometrium was mainly Ca(2+)dependent and partly Ca(2 + )independent and remained
      unaffected by aminoguanidine as an inhibitor of inducible NOS in non-pregnant and
      gestational myometrium. NOS activity per se and endothelial NOS (eNOS) protein
      expression remained unchanged at the middle and term gestation. Neuronal NOS
      (nNOS) and inducible NOS (iNOS) proteins were undetectable. SNP at a high
      concentration of 100 micromol/l failed to modify the spontaneous and ET-1-induced
      rhythmic contractions in non-pregnant and gestational myometrium. Contents of
      N(G)-monomethyl-L-arginine (L-NMMA) plus asymmetric N(G),N(G)-dimethyl-L-arginine
      (ADMA) as endogenous NOS inhibitors and ET-1 within the myometrium were
      significantly decreased at 14th and 20th days of gestation, whereas these were
      significantly increased at term gestation (22nd day) and after delivery. There
      was a significant and positive correlation between endogenous NOS inhibitor
      content and ET-1. ET-1 within the myometrium was significantly increased with a
      concomitant decrease in cyclic GMP production after the intraperitoneal
      application of authentic L-NMMA for 2 weeks, suggesting that the impaired NO
      production with endogenous NOS inhibitors would result in increased ET-1 content.
      These results suggest that endogenous NOS inhibitors such as L-NMMA and ADMA play
      an important role for regulating NO production in rat myometrium. The impaired NO
      production due to accumulated endogenous NOS inhibitors possibly results in
      increased ET-1 content within the myometrium, thereby increasing myometrial
      contractions at term gestation and after delivery.

PMID- 15155820
TI  - Real-time measurement of in vitro transcription.
AB  - We have developed a simple method to measure RNA synthesis in real time. In this
      technique, transcription reactions are performed in the presence of molecular
      beacons that possess a 2'-O-methylribonucleotide backbone. These probes become
      fluorescent as they hybridize to nascent RNA during the course of synthesis. We
      found that molecular beacons synthesized from natural deoxyribonucleotides were
      not suitable, because they are copied by RNA polymerases, generating
      complementary product strands that bind to the molecular beacons, causing a
      conformational change that results in unwanted fluorescence. However, when the
      molecular beacons are synthesized from 2'-O-methylribonucleotides, they are not
      copied and fluorescence is strictly dependent upon transcription of the added
      template. Utilizing these modified molecular beacons, quantitative comparisons
      were made of the activity of a variety of RNA polymerases and the effect of an
      inhibitor of transcription was determined.

PMID- 15155821
TI  - Single-particle tracking for DNA tether length monitoring.
AB  - We describe a simple single-particle tracking approach for monitoring the length
      of DNA molecules in tethered particle motion experiments. In this method, the
      trajectory of a submicroscopic bead tethered by a DNA molecule to a glass surface
      is determined by videomicroscopy coupled to image analysis. The amplitude of
      motion of the bead is measured by the standard deviation of the distribution of
      successive positions of the bead in a given time interval. We were able to
      describe theoretically the variation of the equilibrium value of the amplitude of
      the bead motion with the DNA tether length for the entire applicable DNA length
      range (up to approximately 3500 bp). The sensitivity of the approach was
      illustrated by the evidence obtained for conformational changes introduced into a
      Holliday junction by the binding of the Escherichia coli RuvA protein. An
      advantage of this method is that the trajectory of the tethered bead, rather than
      its averaged motion, is measured, allowing analysis of the conformational
      dynamics of DNA chains at the single-molecule level.

PMID- 15155822
TI  - Oligonucleotide hybridization studied by a surface plasmon diffraction sensor
      (SPDS).
AB  - A novel label-free biosensor concept based on surface plasmon-enhanced
      diffraction by micro- patterned interfaces was applied to the study of
      hybridization reactions of target DNA oligonucleotides (15mers and 75mers) from
      solution to probe DNA oligonucleotides attached via streptavidin to the sensor
      surface. The self-referencing and quadratic signal amplification mechanism of the
      sensor allowed highly sensitive detection of the hybridization process.
      Association and dissociation processes of DNA targets could be recorded in real
      time and used for the quantification of their binding affinities, which differ
      considerably with a single base pair mismatch. An equilibrium titration approach
      was also applied in order to obtain the binding affinities for 15mer targets,
      yielding similar affinity values. The hybridization efficiencies were found to be
      higher for the 15mers than for the 75mers, although the latter contained the same
      recognition sequences. The hybridization efficiency was shown to depend on the
      probe density and reached nearly 100% for the 15mer fully complementary targets
      at a probe density of approximately 1.2 x 10(12) molecules/cm2. Using the assay
      as an end-point determination method, the lowest detectable coverage of a 15mer
      oligonucleotide was at least approximately 1.1 x 10(11) molecules/cm2. The
      diffraction sensing concept offers a completely novel way to integrate a
      reference channel in large-scale, label-free screening applications, to improve
      the stability and to enhance the sensitivity of microarray read-out systems.

PMID- 15155824
TI  - Quantitative analysis of highly parallel transfection in cell microarrays.
AB  - As more genomes are sequenced, we are facing the challenge of rapidly unraveling
      the functions of genes. To that end, cell microarrays have recently been
      described that transfect thousands of nucleic acids in parallel and can be used
      to analyze the phenotypic consequences of such perturbations. As many parameters
      can influence the efficacy of transfection in such a format, we describe some
      important features in manufacturing cell microarrays that may improve reliability
      and efficiency of both plasmid DNA and siRNA transfection. We have also developed
      image analysis software that allows automatic detection of cell clusters,
      quantification of transfection efficiency and levels of expression/extinction of
      genes. Along with cell microarrays, this bioinformatic tool should expedite
      functional exploration of the human genome.

PMID- 15155823
TI  - Balanced-PCR amplification allows unbiased identification of genomic copy changes
      in minute cell and tissue samples.
AB  - Analysis of genomic DNA derived from cells and fresh or fixed tissues often
      requires whole genome amplification prior to microarray screening. Technical
      hurdles to this process are the introduction of amplification bias and/or the
      inhibitory effects of formalin fixation on DNA amplification. Here we demonstrate
      a balanced-PCR procedure that allows unbiased amplification of genomic DNA from
      fresh or modestly degraded paraffin-embedded DNA samples. Following digestion and
      ligation of a target and a control genome with distinct linkers, the two are
      mixed and amplified in a single PCR, thereby avoiding biases associated with PCR
      saturation and impurities. We demonstrate genome-wide retention of allelic
      differences following balanced-PCR amplification of DNA from breast cancer and
      normal human cells and genomic profiling by array-CGH (cDNA arrays, 100 kb
      resolution) and by real-time PCR (single gene resolution). Comparison of balanced
      PCR with multiple displacement amplification (MDA) demonstrates equivalent
      performance between the two when intact genomic DNA is used. When DNA from
      paraffin-embedded samples is used, balanced PCR overcomes problems associated
      with modest DNA degradation and produces unbiased amplification whereas MDA does
      not. Balanced-PCR allows amplification and recovery of modestly degraded genomic
      DNA for subsequent retrospective analysis of human tumors with known outcomes.

PMID- 15155825
TI  - Probing receptor structure/function with chimeric G-protein-coupled receptors.
AB  - Owing its name to an image borrowed from Greek mythology, a chimera is seen to
      represent a new entity created as a composite from existing creatures or, in this
      case, molecules. Making use of various combinations of three basic domains of the
      receptors (i.e., exofacial, transmembrane, and cytoplasmic segments) that couple
      agonist binding into activation of effectors through heterotrimeric G-proteins,
      molecular pharmacology has probed the basic organization, structure/function
      relationships of this superfamily of heptahelical receptors. Chimeric G-protein
      coupled receptors obviate the need for a particular agonist ligand when the
      ligand is resistant to purification or, in the case of orphan receptors, is not
      known. Chimeric receptors created from distant members of the heptahelical
      receptors enable new strategies in understanding how these receptors transduce
      agonist binding into receptor activation and may be able to offer insights into
      the evolution of G-protein-coupled receptors from yeast to humans.

PMID- 15155826
TI  - Getting past the asterisk: the subunit composition of presynaptic nicotinic
      receptors that modulate striatal dopamine release.

PMID- 15155827
TI  - Discovery of novel selective inhibitors of human intestinal carboxylesterase for
      the amelioration of irinotecan-induced diarrhea: synthesis, quantitative
      structure-activity relationship analysis, and biological activity.
AB  - The dose-limiting toxicity of the highly effective anticancer agent 7-ethyl-10-[4
      (1-piperidino)-1-piperidino]carbonyloxy-camptothecin (irinotecan; CPT-11) is
      delayed diarrhea. This is thought to be caused by either bacteria-mediated
      hydrolysis of the glucuronide conjugate of the active metabolite 7-ethyl-10
      hydroxycamptothecin (SN-38) or direct conversion of CPT-11 to SN-38 by
      carboxylesterases (CE) in the small intestine. After drug administration, a very
      high level of CPT-11 is present in the bile; this is deposited into the duodenum,
      the region of the gut with the highest levels of CE activity. Hence, it is likely
      that direct conversion of the drug to SN-38 is partially responsible for the
      diarrhea associated with this agent. In an attempt to ameliorate this toxicity,
      we have applied Target-Related Affinity Profiling to identify novel CE inhibitors
      that are selective inhibitors of the human intestinal enzyme (hiCE). Seven
      inhibitors, all sulfonamide derivatives, demonstrated greater than 200-fold
      selectivity for hiCE compared with the human liver CE hCE1, and none was an
      inhibitor of human acetylcholinesterase or butyrylcholinesterase. Quantitative
      structure-activity relationship (QSAR) analysis demonstrated excellent
      correlations with the predicted versus experimental Ki values (r2 = 0.944) for
      hiCE. Additionally, design and synthesis of a tetrafluorine-substituted
      sulfonamide analog, which QSAR indicated would demonstrate improved inhibition of
      hiCE, validated the computer predictive analyses. These and other phenyl
      substituted sulfonamides compounds are regarded as lead compounds for the
      development of effective, selective CE inhibitors for clinical applications.

PMID- 15155828
TI  - Herbimycin A abrogates nuclear factor-kappaB activation by interacting
      preferentially with the IkappaB kinase beta subunit.
AB  - NF (nuclear factor)-kappaB is known to be a critical transcription factor in
      inflammatory responses. We have reported that herbimycin A, a potent Src tyrosine
      kinase inhibitor, attenuates the NF-kappaB activation triggered by cytokines,
      bacterial endotoxin, and hydrogen peroxide. Accompanying the suppression by this
      agent, NF-kappaB-dependent gene expressions, such as cytokine, chemokine, and
      inducible-type nitric oxide, are specifically inhibited in glial cells. In the
      present study, we attempted to elucidate the possible target protein for
      herbimycin A on this pathway. We demonstrate here that herbimycin A
      preferentially inhibits IKK (IkappaB kinase)beta. Furthermore, substituting
      alanine for the cysteine at 59 (Cys59) in IKKbeta resulted in the insensitivity
      to herbimycin A, suggesting that this compound may interact with the Cys59
      residue located near the catalytic ATP binding site. Taken together, these
      results indicate that herbimycin A can be considered a novel candidate for an
      anti-inflammatory drug agent through its specific inhibition of IKKbeta, which
      results in prevention of the expression of NF-kappaB-dependent genes implicated
      in the pathogenesis of inflammatory responses.

PMID- 15155829
TI  - Insulin activates native and recombinant large conductance Ca(2+)-activated
      potassium channels via a mitogen-activated protein kinase-dependent process.
AB  - Evidence is accumulating that, in addition to regulating peripheral energy
      metabolism, insulin is an important modulator of neuronal function. Indeed, high
      levels of insulin and insulin receptors are expressed in several brain regions
      including the hippocampus. We have shown previously that insulin inhibits
      aberrant synaptic activity in hippocampal neurons via activation of large
      conductance Ca(2+)-activated K+ (BK) channels. In this study, we have examined
      further the effects of insulin on native hippocampal and recombinant (hSlo) BK
      channels expressed in human embryonic kidney (HEK) 293 cells. Pipette or bath
      application of insulin evoked a rapid increase in hippocampal BK channel
      activity, an action caused by activation of insulin receptors because insulin
      like growth factor 1 (IGF-1) failed to mimic insulin action. In parallel studies,
      insulin, applied via the pipette or bath, also activated hSlo channels expressed
      in HEK293 cells. Although phosphoinositide 3-kinase is a key component of insulin
      and IGF-1 receptor signaling pathways, activation of this lipid kinase does not
      underlie the effects of insulin because neither 2-(4-morpholinyl)-8-phenyl-4H-1
      benzopyran-4-one (LY294002) nor wortmannin inhibited or reversed insulin action.
      However, specific inhibitors of mitogen-activated protein kinase (MAPK)
      activation, 2'-amino-3'-methoxyflavone (PD98059) or 1,4-diamino-2,3-dicyano-1,4
      bis(2-aminophenylthio)-butadiene (U0126), attenuated insulin action, indicating
      that a MAPK-dependent mechanism underlies this process. Furthermore, insulin
      activation of this pathway enhances BK channel activity by shifting the Ca(2+)
      sensitivity such that BK channels are active at more hyperpolarized membrane
      potentials. Because postsynaptic BK channels are important regulators of neuronal
      hyperexcitability, insulin-induced activation of BK channels, via stimulation of
      a MAPK-dependent pathway, may be an important process for regulating hippocampal
      function under normal and pathological conditions.

PMID- 15155830
TI  - Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators.
AB  - The lymphocyte potassium channel Kv1.3 is widely regarded as a promising new
      target for immunosuppression. To identify a potent small-molecule Kv1.3 blocker,
      we synthesized a series of 5-phenylalkoxypsoralens and tested them by whole-cell
      patch clamp. The most potent compound of this series, 5-(4-phenylbutoxy)psoralen
      (Psora-4), blocked Kv1.3 in a use-dependent manner, with a Hill coefficient of 2
      and an EC50 value of 3 nM, by preferentially binding to the C-type inactivated
      state of the channel. Psora-4 is the most potent small-molecule Kv1.3 blocker
      known. It exhibited 17- to 70-fold selectivity for Kv1.3 over closely related Kv1
      family channels (Kv1.1, Kv1.2, Kv1.4, and Kv1.7) with the exception of Kv1.5
      (EC50, 7.7 nM) and showed no effect on human ether-a-go-go-related channel,
      Kv3.1, the calcium-activated K+ channels (IKCa1, SK1-SK3, and BKCa), or the
      neuronal NaV1.2 channel. In a test of in vivo toxicity in rats, Psora-4 did not
      display any signs of acute toxicity after five daily subcutaneous injections at
      33 mg/kg body weight. Psora-4 selectively suppressed the proliferation of human
      and rat myelin-specific effector memory T cells with EC50 values of 25 and 60 nM,
      respectively, without persistently suppressing peripheral blood naive and central
      memory T cells. Because autoantigen-specific effector memory T cells contribute
      to the pathogenesis of T cell-mediated autoimmune diseases such as multiple
      sclerosis, Psora-4 and other Kv1.3 blockers may be useful as immunomodulators for
      the therapy of autoimmune disorders.

PMID- 15155831
TI  - Mutations of charged amino acids in or near the transmembrane helices of the
      second membrane spanning domain differentially affect the substrate specificity
      and transport activity of the multidrug resistance protein MRP1 (ABCC1).
AB  - Multidrug resistance protein 1 (MRP1) belongs to the ATP-binding cassette
      superfamily of transport proteins. In addition to drugs, MRP1 mediates the active
      transport of many conjugated and unconjugated organic anions. MRP1 consists of
      two membrane-spanning domains (MSD2 and MSD3) each followed by a nucleotide
      binding domain plus a third NH2-terminal MSD1. MSD2 contains transmembrane (TM)
      helices 6 through 11, and previously, we identified two charged residues in TM6
      as having important but markedly different roles in MRP1 transport activity and
      substrate specificity by characterizing mutants containing nonconservative
      substitutions of Lys332 and Asp336. We have now extended these studies and found
      that the same-charge TM6 mutant K332R, like the nonconservatively substituted
      Lys332 mutants, exhibits a selective decrease in leukotriene C4 (LTC4) transport,
      associated with substantial changes in both Km and Vmax and LTC4 binding. The
      overall organic anion transport activity of the same-charge mutant of Asp336
      (D336E) also remained very low, as observed for D336R. In addition,
      nonconservative substitutions of TM6-associated Lys319 and Lys347 resulted in a
      selective decrease in GSH transport. Of eight other charged residues in or
      proximal to TM7 to TM11 that were investigated, nonconservative substitutions of
      three of them [Lys396 (TM7), Asp436 (TM8), and Arg593 (TM11)] caused a
      substantial and global reduction in transport activity. However, unlike TM6
      Asp336, wild-type transport activity could be reestablished in these MRP1 mutants
      by conservative substitutions. We conclude that MSD2-charged residues in or
      proximal to TM6, TM7, TM8, and TM11 play critical but differential roles in MRP1
      transport activity and substrate specificity.

PMID- 15155832
TI  - Adenosine triphosphate acts as both a competitive antagonist and a positive
      allosteric modulator at recombinant N-methyl-D-aspartate receptors.
AB  - ATP and glutamate are fast excitatory neurotransmitters in the central nervous
      system acting primarily on ionotropic P2X and glutamate [N-methyl-D-aspartate
      (NMDA) and non-NMDA] receptors, respectively. Both neurotransmitters regulate
      synaptic plasticity and long-term potentiation in hippocampal neurons. NMDA
      receptors are responsible primarily for the modulatory action of glutamate, but
      the mechanism underlying the modulatory effect of ATP remains uncertain. In the
      present study, the effect of ATP on recombinant NR1a + 2A, NR1a + 2B, and NR1a +
      2C NMDA receptors expressed in Xenopus laevis oocytes was investigated. ATP
      inhibited NR1a + 2A and NR1a + 2B receptor currents evoked by low concentrations
      of glutamate but potentiated currents evoked by saturating glutamate
      concentrations. In contrast, ATP potentiated NR1a + 2C receptor currents evoked
      by nonsaturating glutamate concentrations. ATP shifted the glutamate
      concentration-response curve to the right, indicating a competitive interaction
      at the agonist binding site. ATP inhibition and potentiation of glutamate-evoked
      currents was voltage-independent, indicating that ATP acts outside the membrane
      electric field. Other nucleotides, including ADP, GTP, CTP, and UTP, inhibited
      glutamate-evoked currents with different potencies, revealing that the inhibition
      is dependent on both the phosphate chain and nucleotide ring structure. At high
      concentrations, glutamate outcompetes ATP at the agonist binding site, revealing
      a potentiation of the current. This effect must be caused by ATP binding at a
      separate site, where it acts as a positive allosteric modulator of channel
      gating. A simple model of the NMDA receptor, with ATP acting both as a
      competitive antagonist at the glutamate binding site and as a positive allosteric
      modulator at a separate site, reproduced the main features of the data.

PMID- 15155833
TI  - The constitutive active/androstane receptor regulates phenytoin induction of
      Cyp2c29.
AB  - Many cytochrome P450 isoforms are known to be drug-inducible. The anticonvulsant
      phenytoin has been reported to be an inducer of human CYP2B6, CYP3A4, and murine
      CYP2C29. However, the molecular mechanism mediating phenytoin induction remains
      unclear. Herein, we used in vivo and in vitro gene reporter assays of the Cyp2c29
      promoter to delineate the phenytoin-response activity to a phenytoin-responsive
      module located at -1371 kb upstream of the Cyp2c29 translation start site. The
      phenytoin-responsive module, consisting of two motifs of two imperfect direct
      repeat hexamers spaced by four nucleotides and a putative CCAAT/enhancer-binding
      protein-binding site, mediated luciferase reporter induction by phenytoin in
      mouse livers in vivo and was activated by CAR in HepG2 cells. Hepatic CYP2C29
      mRNA was induced by phenytoin in wild-type but not in CAR-null mice, indicating
      that constitutive active or androstane receptor (CAR) regulates phenytoin-induced
      transcription of the Cyp2c29 gene. Furthermore, the constitutive levels of
      CYP2C29 mRNA were reduced approximately 77-fold in CAR-null mice compared with
      those in the wild-type mice, suggesting that CAR may also regulate the
      constitutive expression of the Cyp2c29 gene either directly or indirectly.

PMID- 15155834
TI  - Interaction of heterogeneous nuclear ribonucleoprotein A1 with cytochrome P450
      2A6 mRNA: implications for post-transcriptional regulation of the CYP2A6 gene.
AB  - The human xenobiotic-metabolizing enzyme cytochrome P450, CYP2A6, catalyzes the
      bioactivation of a number of carcinogens and drugs and is overexpressed in cases
      of liver diseases, such as cirrhosis, viral hepatitis, and parasitic infestation,
      and in certain tumor cells. This suggests that CYP2A6 may be a major liver
      catalyst in pathological conditions. In the present study, we have addressed
      molecular mechanisms underlying the regulation of the CYP2A6 gene. We present
      evidence of several proteins present in human hepatocytes that interact
      specifically with the 3'-untranslated region (UTR) of CYP2A6 mRNA. Biochemical
      and immunological evidence show that the RNA-protein complex of highest intensity
      contains the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 or a closely
      related protein. Mapping of the hnRNP A1 binding site within CYP2A6 3'-UTR
      reveals that the smallest portion of RNA supporting significant binding consists
      of 111 central nucleotides of the 3'-UTR. Our studies also indicate that hnRNPA1
      from HepG2 cancer cells exhibits modified binding characteristics to the CYP2A6
      3'-UTR compared with primary hepatocytes. We found that the level of CYP2A6 mRNA
      remains high in conditions of impaired transcription in primary human
      hepatocytes, showing that CYP2A6 expression can be affected post
      transcriptionally in conditions of cellular stress. Our results indicate that the
      post-transcriptional regulation involves interaction of the hnRNP A1 protein with
      CYP2A6 mRNA. The present data suggest that hnRNPA1 is a critical regulator of
      expression of the human CYP2A6 gene and support the notion that this P450 isoform
      may be of particular significance in stressed human liver cells.

PMID- 15155835
TI  - Capsaicin potentiates wild-type and mutant cystic fibrosis transmembrane
      conductance regulator chloride-channel currents.
AB  - To examine the effects of capsaicin on cystic fibrosis transmembrane conductance
      regulator (CFTR), we recorded wild-type and mutant CFTR chloride-channel currents
      using patch-clamp methods. The effects of capsaicin were compared with those of
      genistein, a well-characterized CFTR activator. In whole-cell experiments,
      capsaicin potentiates cAMP-stimulated wild-type CFTR currents expressed in NIH
      3T3 cells or Chinese hamster ovary cells in a dose-dependent manner with a
      maximal response approximately 60% of that with genistein and an apparent Kd of
      48.4 +/- 6.8 microM. In cell-attached recordings, capsaicin alone fails to
      activate CFTR in cells that show negligible basal CFTR activity, indicating that
      capsaicin does not stimulate the cAMP cascade. The magnitude of potentiation with
      capsaicin depends on the channel activity before drug application; the lower the
      prestimulated Po, the higher the potentiation. Single-channel kinetic analysis
      shows that capsaicin potentiates CFTR by increasing the opening rate and
      decreasing the closing rate of the channel. Capsaicin may act as a partial
      agonist of genistein because the maximally enhanced wild-type CFTR currents with
      genistein are partially inhibited by capsaicin. Capsaicin increases DeltaR-CFTR,
      a protein kinase A (PKA)-independent, constitutively active channel, in cell
      attached patches. In excised inside-out patches, capsaicin potentiates the PKA
      phosphorylated, ATP-dependent CFTR activity. Both capsaicin and genistein
      potentiate the cAMP-stimulated G551D-CFTR, DeltaF508-CFTR, and 8SA mutant channel
      currents. The binding site for capsaicin is probably located at the cytoplasmic
      domain of CFTR, because pipette application of capsaicin fails to potentiate CFTR
      activity. In conclusion, capsaicin is a partial agonist of genistein in
      activation of the CFTR chloride channel. Both compounds affect ATP-dependent
      gating of CFTR.

PMID- 15155836
TI  - Signal transducer and activator of transcription 3 activation by the delta-opioid
      receptor via Galpha14 involves multiple intermediates.
AB  - The hematopoietic-specific Galpha14 links a variety of G protein-coupled
      receptors to phospholipase Cbeta (PLCbeta) stimulation. Recent studies reveal
      that several Galpha subunits are capable of activating signal transducer and
      activator of transcription (STAT) proteins. In the present study, we investigated
      the mechanism by which Galpha14 mediates receptor-induced stimulation of STAT3.
      In human embryonic kidney 293 cells, coexpression of Galpha14 with delta-opioid
      receptor supported [D-Pen2, D-Pen5]enkephalin (DPDPE)-induced STAT3
      phosphorylations at both Tyr705 and Ser727 in a pertussis toxin-insensitive
      manner. The constitutively active Galpha4QL mutant also induced STAT3
      phosphorylations at these sites and promoted STAT3-dependent luciferase activity.
      Requirements for PLCbeta, protein kinase C (PKC), and calmodulin-dependent kinase
      II (CaMKII) in Galpha14QL-induced STAT3 activation were demonstrated by their
      respective inhibitors as well as by coexpression of their dominant-negative
      mutants. Inhibition of c-Src and Janus kinase 2 and 3 activities abolished STAT3
      activation induced by Galpha14QL, but no physical association between Galpha14QL
      and c-Src could be detected by coimmunoprecipitation. Various intermediates along
      the extracellular signal-regulated kinase signaling cascade were apparently
      required for Galpha14QL-induced STAT3 activation; they included Ras/Rac1, Raf-1,
      and mitogen-activated protein kinase kinase-1/2. In contrast, functional blockade
      of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and
      phosphatidylinositol-3 kinase had no effect on Galpha14QL-induced responses.
      PLCbeta, PKC, and CaMKII were shown to be involved in Galpha14QL-mediated c-Src
      phosphorylation. Similar results were obtained with human erythro-leukemia cells
      upon DPDPE treatment. These results demonstrate for the first time that Galpha14
      activation can lead to STAT3 stimulation via a complex signaling network
      involving multiple intermediates.

PMID- 15155837
TI  - Down-regulation of soluble guanylyl cyclase expression by cyclic AMP is mediated
      by mRNA-stabilizing protein HuR.
AB  - We analyzed whether the cyclic AMP induced down-regulation of the nitric oxide
      (NO) receptor soluble guanylyl cyclase (sGC) is mediated by the mRNA-protecting
      protein HuR. Exposure (up to 24 h) of isolated rat aortic segments to the
      activator of adenylyl cyclase, forskolin (10 microM), and to both activators of
      cAMP-stimulated protein kinase (PKA), 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole-3',5'-cyclic monophosphorothioate, Spisomer (Sp-5,6
      DCl-cBIMPS; 400 nM), and N6-phenyl-cAMP (10 microM), strongly reduced
      sGCalpha1beta1 and HuR protein and mRNA expression in a time-dependent and
      actinomycin D (10 microM)-sensitive fashion. In vitro degradation of sGCalpha1
      and beta1 poly(A)+ mRNA by native rat aortic protein was markedly increased by
      pretreatment of intact aortas with forskolin. Native protein extract from rat
      aorta shifted the electrophoretic mobility of biotin-labeled riboprobes from the
      3'-untranslated region of sGCalpha1 and beta1 mRNA, and these bands was
      supershifted by a monoclonal antibody directed against the mRNA-stabilizing
      protein HuR. Forskolin decreased the HuR-sGCalpha1 and beta1 mRNA interaction and
      HuR protein expression in rat aorta, and this was prevented by the PKA inhibitory
      cAMP analog 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In cultured
      smooth muscle cells from rat aorta, forskolin induced a rapid increase in Fos/p
      Fos protein levels and activator protein 1 (AP-1) binding activity. Inhibition of
      this transcription factor by an AP-1 decoy prevented the forskolin-induced down
      regulation of HuR. We conclude that forskolin/cAMP decrease the expression of
      heterodimeric sGC in rat aortic smooth muscle cells via activation of Fos/AP-1,
      which decreases the expression of HuR and thus destabilizes the sGCalpha1 and
      beta1 mRNA.

PMID- 15155838
TI  - Transmembrane domains I and II of the gamma-aminobutyric acid transporter GAT-4
      contain molecular determinants of substrate specificity.
AB  - The sodium- and chloride-dependent GABA transporters GABA transporter (GAT) 1 to
      4 in the central nervous system enable efficient synaptic transmission by
      removing the neurotransmitter from the cleft. Taurine interacts only weakly with
      the GABA transporter GAT-4 (IC50 approximately 1.6 mM). Glutamate-61 is located
      in the conserved transmembrane domain I of GAT-4, whereas in the related taurine
      transporter taurine transporter (TAUT), glycine occupies the equivalent position.
      [3H]GABA uptake by the GAT-4 E61G mutant becomes markedly more sensitive to
      inhibition by taurine (IC50 approximately 0.26 mM). Replacement of cysteine-94,
      located in the conserved transmembrane domain II of GAT-4, to its TAUT
      counterpart serine, results only in a modest increase in the ability of taurine
      to inhibit GABA uptake. However, introduction of glycine at this position
      decreases the IC50 for taurine by approximately 8-fold (IC50 approximately 0.20
      mM). The inhibitory potency of taurine is inversely correlated with the volume of
      the side chain of the amino acid residue introduced at positions 61 and 94. It is
      striking that the IC50 for taurine of the E61G/C94G double mutant is decreased by
      approximately 35-fold (IC50 approximately 0.05 mM), and this inhibition of GABA
      transport is competitive. Changes in the inhibitory potency of the mutants
      described are also observed with beta-ala-nine and GABA, although they are much
      less pronounced. Our results suggest that determinants on transmembrane domains I
      and II can influence the specificity of the substrate binding pocket. The size of
      the side chain at positions 61 and 94 seems to determine the ability of substrate
      and substrate analogs to interact with the transporter.

PMID- 15155839
TI  - Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase
      dependent up-regulation of serotonin transporters involves both transporter
      trafficking and activation.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) transporters (SERTs) are critical
      determinants of synaptic 5-HT inactivation and the targets for multiple drugs
      used to treat psychiatric disorders. In support of prior studies, we found that
      short-term (5-30 min) application of the adenosine receptor (AR) agonist 5'-N
      ethylcarboxamidoadenosine (NECA) induces an increase in 5-HT uptake Vmax in rat
      basophilic leukemia 2H3 cells that is enhanced by pretreatment with the cGMP
      phosphodiesterase inhibitor sildenafil. NECA stimulation is blocked by the A3 AR
      antagonist 3-ethyl-5-benzyl-2-methyl-phenylethynyl-6-phenyl-1,4(+/
      )dihydropyridine-3,5-dicarboxylate (MRS1191), by the phospholipase C inhibitor 1
      (6-[[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl] amino]hexyl)-1H-pyrrole-2,5
      dione (U73122), by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid acetoxymethyl ester, and by the guanyl cyclase
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Hydroxylamine, a nitric
      oxide donor, and 8-bromo-cGMP, a membrane-permeant analog of cGMP, mimic the
      effects of NECA on 5-HT uptake, whereas the protein kinase G (PKG) inhibitor N-[2
      (methylamino)ethy]-5-isoquinoline-sulfonamide (H8) blocks NECA, hydroxylamine,
      and 8-bromo-cGMP effects. NECA stimulation activates p38 mitogen-activated
      protein kinase (MAPK), whereas p38 MAPK inhibitors block NECA stimulation of SERT
      activity, as does the protein phosphatase 2A (PP2A) inhibitor calyculin A. 5-HT
      displaceable [125I]3beta-(4-iodophenyl)-tropane-2beta-carboxylic acid methylester
      tartrate (RTI-55) whole-cell binding is increased by NECA or sildenafil, and both
      surface binding and cell surface SERT protein are elevated after NECA or
      sildenafil stimulation of AR/SERT-cotransfected Chinese hamster ovary cells.
      Whereas p38 MAPK inhibition blocks NECA stimulation of 5-HT activity, it fails to
      blunt stimulation of SERT surface density. Moreover, inactivation of existing
      surface SERTs fails to eliminate NECA stimulation of SERT. Together, these
      results reveal two PKG-dependent pathways supporting rapid SERT regulation by A3
      ARs, one leading to enhanced SERT surface trafficking, and a separate, p38 MAPK
      dependent process augmenting SERT intrinsic activity.

PMID- 15155840
TI  - Ceramide negatively regulates glutathione S-transferase gene transactivation via
      repression of hepatic nuclear factor-1 that is degraded by the ubiquitin
      proteasome system.
AB  - The level of cellular ceramide, an apoptotic rheostat, is increased by
      sphingomyelinase or de novo synthesis. The expression of the glutathione S
      transferase (GST) gene, whose induction accounts for cell viability, is regulated
      by activation of CCAAT/enhancer binding protein-beta (C/EBPbeta) and NF-E2
      related factor-2 (Nrf2). Hepatic nuclear factor-1 (HNF1) is a transcription
      factor necessary for cell survival. This study investigated the role of HNF1 in
      GSTA2 gene transactivation, the ubiquitin proteasomal degradation of HNF1, and
      the inhibition of activating HNF1 by ceramide for GSTA2 repression. C2-ceramide
      (C2), a cell-permeable analog, repressed the GSTA2 expression in H4IIE cells,
      whereas dihydro-C2, an inactive analog, had no effect. Immunoblot,
      immunocytochemical, and gel shift analyses revealed that C2 decreased the level
      of nuclear HNF1 and protein binding to the HNF response element (HRE). Deletion
      of the HRE or the GSTA2 gene promoter region containing the HRE reduced
      luciferase reporter expression. Immunoprecipitation and immunoblot analyses
      showed that C2 decreased the level of ubiquitinated HNF1, which was reversed by
      treatment with MG132, a proteasome inhibitor. C2 suppressed GSTA2 induction by
      oltipraz via inhibition of inducible HNF1 DNA binding. The functional role of HRE
      for C2 repression of GSTA2 gene transactivation by oltipraz was verified by both
      the luciferase reporter gene expression and the transfection experiment with
      DeltaHNF-pGL-1651 lacking the HRE. C2 similarly repressed the induction of GSTA2
      promoter-luciferase by tert-butylhydroquinone via HNF1 suppression, suggesting
      that constitutive HNF1 activation is required for GSTA2 induction. C2 also
      inhibited GSTA3/5 expression. In conclusion, the HRE in the GSTA2 promoter region
      is functionally active for the constitutive and inducible gene expression, and
      ceramide inhibits GST gene transactivation through decrease in nuclear HNF1,
      which is degraded by the ubiquitin proteasome system.

PMID- 15155841
TI  - High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug
      transporter.
AB  - Tyrosine kinase inhibitors (TKIs) are promising new agents for specific
      inhibition of malignant cell growth and metastasis formation. Because most of the
      TKIs have to reach an intracellular target, specific membrane transporters may
      significantly modulate their effectiveness. In addition, the hydrophobic TKIs may
      interact with so-called multidrug transporters and thus alter the cellular
      distribution of unrelated pharmacological agents. In the present work, we show
      that certain TKIs, already in the clinical phase of drug development, directly
      interact with the ABCG2 multidrug transporter protein with a high affinity. We
      found that in several in vitro assay systems, STI-571 (Gleevec; imatinib
      mesylate), ZD1839 (Iressa; gefitinib), and N-[4-[(3-bromophenyl)amino]-6
      quinazolinyl]-2-butynamide (EKI-785) interacted with ABCG2 at submicromolar
      concentrations, whereas other multidrug transporters, human multidrug resistance
      protein (P-glycoprotein, ABCB1) and human multidrug resistance protein 1 (ABCC1),
      showed much lower reactivity toward these agents. Low concentrations of the TKIs
      examined selectively modulated ABCG2-ATPase activity, inhibited ABCG2-dependent
      active drug extrusion, and significantly affected drug resistance patterns in
      cells expressing ABCG2. Our results indicate that multidrug resistance protein
      modulation by TKIs may be an important factor in the clinical treatment of cancer
      patients. These data also raise the possibility that an extrusion of TKIs by
      multidrug transporters, e.g., ABCG2, may be involved in tumor cell TKI
      resistance.

PMID- 15155842
TI  - DNA damage-processing pathways involved in the eukaryotic cellular response to
      anticancer DNA cross-linking drugs.
AB  - We used a panel of isogenic Saccharomyces cerevisiae strains compromised in
      several different DNA damage-processing pathways to assess in vivo processing of
      DNA adducts induced by four cross-linking anticancer drugs. By examining
      cytotoxicity profiles, cell cycle arrest patterns, and determining recombination
      and mutation frequencies, we found that cisplatin-, nitrogen mustard-, mitomycin
      , and carmustine-induced DNA adducts in S. cerevisiae are processed by components
      of the nucleotide excision repair (NER), recombination repair (RR), and
      translesion synthesis (TLS) pathways, with substantially different contributions
      of each pathway for the drugs studied here. In contrast to previous studies that
      used single pathway-compromised strains to identify genes that mediate
      sensitivity to DNA cross-linking drugs, we used strains that were compromised in
      multiple pathways. By doing so, we were able to establish several functions that
      were previously unknown and interconnections between different DNA damage
      processing pathways. To our surprise, we found that for cisplatin-induced
      cytotoxicity, TLS and RR contribute to survival to a significant extent. In the
      case of nitrogen mustard DNA adduct processing, equal involvement of two major
      pathways was established: one that requires functional RR and NER components and
      one that requires functional TLS and NER components. These data reveal the
      complexity of DNA cross-link processing that, in many cases, requires
      interactions of components from several different DNA damage-processing systems.
      We demonstrate the usefulness of yeast strains with multiple simultaneous defects
      in DNA damage-processing pathways for studying the modes of action of anticancer
      drugs.

PMID- 15155843
TI  - Activation of cyclic AMP-dependent protein kinase inhibits the desensitization
      and internalization of metabotropic glutamate receptors 1a and 1b.
AB  - In this study, we characterized the effects of activation of cyclic AMP-dependent
      protein kinase (PKA) on the internalization and functional coupling of the
      metabotropic glutamate receptor (mGluR1) splice variants mGluR1a and mGluR1b.
      Using an enzyme-linked immunosorbent assay technique to assess receptor
      internalization, we found that the glutamate-induced internalization of mGluR1a
      or mGluR1b transiently expressed in human embryonic kidney (HEK) 293 cells was
      inhibited by coactivation of endogenous beta2-adrenoceptors with isoprenaline or
      by direct activation of adenylyl cyclase with forskolin. The PKA inhibitor N-(2
      [p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H89)
      blocked the effects of both isoprenaline and forskolin. The heterologous
      internalization of the mGluR1 splice variants triggered by carbachol was also
      inhibited by isoprenaline and forskolin in a PKA-sensitive fashion, whereas the
      constitutive (agonist-independent) internalization of mGluR1a was inhibited only
      modestly by PKA activation. Using inositol phosphate (IP) accumulation in cells
      prelabeled with [3H]inositol to assess receptor coupling, PKA activation
      increased basal IP accumulation in mGluR1a receptor-expressing cells and also
      increased glutamate-stimulated IP accumulation in both mGluR1a- and mGluR1b
      expressing cells, but only at short times of glutamate addition. Furthermore, PKA
      activation completely blocked the carbachol-induced heterologous desensitization
      of glutamate-stimulated IP accumulation in both mGluR1a- and mGluR1b-expressing
      cells. In coimmunoprecipitation experiments, the ability of glutamate to increase
      association of GRK2 and arrestin-2 with mGluR1a and mGluR1b was inhibited by PKA
      activation with forskolin. Together, these results indicate that PKA activation
      inhibits the agonist-induced internalization and desensitization of mGluR1a and
      mGluR1b, probably by reducing their interaction with GRK2 and nonvisual
      arrestins.

PMID- 15155844
TI  - Alternative processing events in human FMO genes.
AB  - In humans, flavin-containing monooxygenase (FMO) functional diversity is
      determined by the expression of five FMO genes, named FMO1 to FMO5, and their
      variants. In this study, we systematically analyzed transcripts of FMO1 to FMO5
      in different human tissues by reverse-transcription-polymerase chain reaction and
      identified a large number of splice variants. Exon skipping was the major
      splicing event observed. Normally spliced transcripts were generally the
      prominent transcript detected. For FMO1, FMO2, and FMO3, two to three different
      splice variants were identified, and their corresponding expression was always
      low in the tissues examined. For FMO5 and particularly for FMO4, more complex
      alternative splice patterns were observed, with five and seven splice variants
      detected, respectively. Most identified FMO splice variants either caused a frame
      shift or lacked essential functional sites. The corresponding transcripts were
      therefore incapable of encoding a functional enzyme and were not analyzed further
      in this study. However, a common in-frame exon 3- (exon 4 for FMO4) deleted
      variant, leading to the deletion of 63 amino acids, was identified for FMO1,
      FMO3, FMO4, and FMO5. To examine the functional importance of exon 3-deletion,
      FMO1, FMO3, FMO4 and the corresponding exon-deleted proteins were expressed as
      fusion proteins. Activity studies were done with two selective functional FMO
      substrates, methimazole, and 10-(N,N-dimethylaminopentyl)-2
      (trifluoromethyl)phenothiazine and exon 3- (exon 4 for FMO4) deleted FMOs were
      not able to catalyze the S- and N-oxygenation of these substrates, respectively.
      It is not clear whether these FMO splice variants can oxygenate other substrates,
      including those that remain to be discovered.

PMID- 15155845
TI  - Subunit composition and pharmacology of two classes of striatal presynaptic
      nicotinic acetylcholine receptors mediating dopamine release in mice.
AB  - Pharmacological evaluation of nicotine-stimulated dopamine release from striatum
      has yielded data consistent with activation of a single population of nicotinic
      acetylcholine receptors (nAChR). However, discovery that alpha-conotoxin MII
      (alpha-CtxMII) partially inhibits the response indicates that two classes of
      presynaptic nAChRs mediate dopamine release. We have investigated the
      pharmacology and subunit composition of these two classes of nAChR. Inhibition of
      nicotine-stimulated dopamine release from mouse striatal synaptosomes by alpha
      CtxMII occurs within minutes; recovery is slow. The IC50 is 1 to 3 nM. alpha
      CtxMII-sensitive and -resistant components have significant differences in
      pharmacology. The five agonists tested were more potent at activating the alpha
      CtxMII-sensitive nAChRs; indeed, this receptor is the highest affinity functional
      nAChR found, so far, in mouse brain. In addition, cytisine was more efficacious
      at the alpha-CtxMII-sensitive sites. Methyllycaconitine was 9-fold more potent at
      inhibiting the alpha-CtxMII-sensitive sites, whereas dihydro-beta-erythroidine
      was a 7-fold more potent inhibitor of the alpha-CtxMII-resistant response. Both
      the transient and persistent phases of nicotine-stimulated dopamine release were
      partially inhibited by alpha-CtxMII with equal potency. The subunit composition
      of functional nAChRs, was assessed in mice with null mutations for individual
      nAChR subunits. The beta2 subunit is an absolute requirement for both classes. In
      contrast, deletion of beta4 or alpha7 subunits had no effect. The alpha-CtxMII
      sensitive response requires beta3 and is partially dependent upon alpha4
      subunits, probably alpha6beta3beta2 and alpha4alpha6beta3beta2, whereas the alpha
      CtxMII-resistant release requires alpha4 and is partially dependent upon alpha5
      subunits, probably alpha4beta2 and alpha4alpha5beta2.

PMID- 15155846
TI  - Function of the ABC signature sequences in the human multidrug resistance protein
      1.
AB  - Human multidrug resistance protein 1 (MRP1) is a membrane ATP-binding cassette
      transporter that confers multidrug resistance to tumor cells by effluxing
      intracellular drugs in an ATP-dependent manner. The mechanisms by which transport
      occurs and by which ATP hydrolysis is coupled to drug transport are not fully
      elucidated. In particular, the function of the signature sequences in the
      nucleotide binding domains (NBDs) of MRP1 is unknown. We therefore investigated
      the effect of mutation of the signature sequences (G771D and G1433D) and of the
      Walker A motifs (K684M and K1333M) in the NBDs on the 8-azido-[alpha-32P]ATP
      photolabeling and 8-azido-[alpha-32P]ADP vanadate trapping of MRP1. Both
      mutations in the Walker A motif almost completely inhibited the labeling of the
      mutated NBD with 8-azido-[alpha-32P]ATP but not the labeling of the other intact
      NBD. In contrast, the G771D mutation in the signature sequence of NBD1 enhanced
      the labeling of NBD1 but slightly decreased the labeling of NBD2. The G1433D
      mutation in the signature motif of NBD2 enhanced the labeling of NBD2 but did not
      affect the labeling of NBD1. These effects were all substrate-independent.
      Photolabeling of NBD2 and a very slight photolableing of NBD1 were detectable
      under vanadate trapping conditions with 8-azido-[alpha-32P]ATP. Trapping at both
      NBD1 and NBD2 was almost completely inhibited by K684M and K1333M mutations and
      by the K684M/K1333M double mutation. The G771D mutation completely inhibited
      trapping at NBD2 and considerably inhibited trapping at NBD1. However, whereas
      the G1433D mutation also considerably inhibited trapping at NBD1, it only
      partially inhibited trapping of NBD2, and the trapping could still be enhanced by
      leukotriene C4. Our findings suggest that both signature sequences of MRP1 are
      involved in ATP hydrolysis and must be intact for the ATP hydrolysis and the
      transport by MRP1.

PMID- 15155848
TI  - Sequence context effect on the structure of nitrous acid induced DNA interstrand
      cross-links.
AB  - In the preceding paper in this journal, we described the solution structure of
      the nitrous acid cross-linked dodecamer duplex [d(GCATCCGGATGC)]2 (the cross
      linked guanines are underlined). The structure revealed that the cross-linked
      guanines form a nearly planar covalently linked 'G:G base pair', with the
      complementary partner cytidines flipped out of the helix. Here we explore the
      flanking sequence context effect on the structure of nitrous acid cross-links in
      [d(CG)]2 and the factors allowing the extrahelical cytidines to adopt such fixed
      positions in the minor groove. We have used NMR spectroscopy to determine the
      solution structure of a second cross-linked dodecamer duplex, [d(CGCTACGTAGCG)]2,
      which shows that the identity of the flanking base pairs significantly alters the
      stacking patterns and phosphate backbone conformations. The cross-linked guanines
      are now stacked well on adenines preceding the extrahelical cytidines,
      illustrating the importance of purine- purine base stacking. Observation of an
      imino proton resonance at 15.6 p.p.m. provides evidence for hydrogen bonding
      between the two cross-linked guanines. Preliminary structural studies on the
      cross-linked duplex [d(CGCGACGTCGCG)]2 show that the extrahelical cytidines are
      very mobile in this sequence context. We suggest that favorable van der Waals
      interactions between the cytidine and the adenine 2 bp away from the cross-link
      localize the cytidines in the previous cross-linked structures.

PMID- 15155847
TI  - Solution structure of a nitrous acid induced DNA interstrand cross-link.
AB  - Nitrous acid is a mutagenic agent. It can induce interstrand cross-links in
      duplex DNA, preferentially at d(CpG) steps: two guanines on opposite strands are
      linked via a single shared exocyclic imino group. Recent synthetic advances have
      led to the production of large quantities of such structurally homogenous cross
      linked duplex DNA. Here we present the high resolution solution structure of the
      cross-linked dodecamer [d(GCATCCGGATGC)]2 (the cross-linked guanines are
      underlined), determined by 2D NMR spectroscopy, distance geometry, restrained
      molecular dynamics and iterative NOE refinement. The cross-linked guanines form a
      nearly planar covalently linked 'G:G base pair' with only minor propeller
      twisting, while the cytidine bases of their normal base pairing partners have
      been flipped out of the helix and adopt well defined extrahelical positions in
      the minor groove. On the 5'-side of the cross-link, the minor groove is widened
      to accommodate these extrahelical bases, and the major groove becomes quite
      narrow at the cross-link. The cross-linked 'G:G base pair' is well stacked on the
      spatially adjacent C:G base pairs, particularly on the 3'-side guanines. In
      addition to providing the first structure of a nitrous acid cross-link in DNA,
      these studies could be of major importance to the understanding of the mechanisms
      of nitrous acid cross-linking and mutagenicity, as well as the mechanisms
      responsible for its repair in intracellular environments. It is also the shortest
      DNA cross-link structure to be described.

PMID- 15155849
TI  - Influence of structural variation on nuclear localization of DNA-binding
      polyamide-fluorophore conjugates.
AB  - A pivotal step forward in chemical approaches to controlling gene expression is
      the development of sequence-specific DNA-binding molecules that can enter live
      cells and traffic to nuclei unaided. DNA-binding polyamides are a class of
      programmable, sequence-specific small molecules that have been shown to influence
      a wide variety of protein-DNA interactions. We have synthesized over 100
      polyamide-fluorophore conjugates and assayed their nuclear uptake profiles in 13
      mammalian cell lines. The compiled dataset, comprising 1300 entries, establishes
      a benchmark for the nuclear localization of polyamide-dye conjugates. Compounds
      in this series were chosen to provide systematic variation in several structural
      variables, including dye composition and placement, molecular weight, charge,
      ordering of the aromatic and aliphatic amino-acid building blocks and overall
      shape. Nuclear uptake does not appear to be correlated with polyamide molecular
      weight or with the number of imidazole residues, although the positions of
      imidazole residues affect nuclear access properties significantly. Generally
      negative determinants for nuclear access include the presence of a beta-Ala-tail
      residue and the lack of a cationic alkyl amine moiety, whereas the presence of an
      acetylated 2,4-diaminobutyric acid-turn is a positive factor for nuclear
      localization. We discuss implications of these data on the design of polyamide
      dye conjugates for use in biological systems.

PMID- 15155850
TI  - Structural characterization of an intermolecular RNA-RNA interaction involved in
      the transcription regulation element of a bipartite plant virus.
AB  - The 34-nucleotide trans-activator (TA) located within the RNA-2 of Red clover
      necrotic mosaic virus folds into a simple hairpin. The eight-nucleotide TA loop
      base pairs with eight complementary nucleotides in the TA binding sequence (TABS)
      of the capsid protein subgenomic promoter on RNA-1 and trans-activates subgenomic
      RNA synthesis. Short synthetic oligoribonucleotide mimics of the RNA-1 TABS and
      the RNA-2 TA form a weak 1:1 bimolecular complex in vitro with a K(a) of 5.3 x
      10(4) M(-1). K(a) determination for a series of RNA-1 and RNA-2 mimic variants
      indicated optimum stability is obtained with seven-base complementarity. Thermal
      denaturation and NMR show that the RNA-1 TABS 8mers are weakly ordered in
      solution while RNA-2 TA oligomers form the predicted hairpin. NMR diffusion
      studies confirmed RNA-1 and RNA-2 oligomer complex formation in vitro. MC-Sym
      generated structural models suggest that the bimolecular complex is composed of
      two stacked helices, one being the stem of the RNA-2 TA hairpin and the other
      formed by the intermolecular base pairing between RNA-1 and RNA-2. The RCNMV TA
      structural model is similar to those for the Simian retrovirus frameshifting
      element and the Human immunodeficiency virus-1 dimerization kissing hairpins,
      suggesting a conservation of form and function.

PMID- 15155851
TI  - The high-affinity Sp1 binding site in the HTLV-1 promoter contributes to Tax
      independent basal expression.
AB  - Transcriptional activation of human T-cell leukemia virus type 1 (HTLV-1)
      requires many cellular proteins and the virally encoded transcription factor Tax.
      Tax binds the three viral cAMP-response elements (CREs) with ATF/CREB (activating
      transcription factor/cAMP-response element-binding protein) and recruits the
      cellular coactivators CBP/p300. HTLV-1 also utilizes other cellular transcription
      factors that bind to the promoter to regulate transcription. One of these
      factors, Sp1, has been shown to bind to the viral promoter at two elements; one
      located within the third viral CRE, and the second located between the second and
      third viral CREs. The functional significance of Sp1 binding at each of these
      regions of the viral promoter is not completely understood. We set out to
      characterize Sp1 binding and to evaluate the functional significance of Sp1, both
      in the absence and presence of Tax. We found that Sp1 binds preferentially to the
      element located between the second and third viral CREs, and modestly activates
      transcription in vitro and in vivo. Sp1 was detected at the integrated HTLV-1
      promoter in vivo. Surprisingly, point mutagenesis of the strong Sp1 binding site
      rendered the HTLV-1 reporter plasmid insensitive to Sp1 activation, and
      dramatically reduced basal transcription in vivo. These data indicate a role for
      Sp1 in basal level transcription of HTLV-1.

PMID- 15155852
TI  - Frequency of gaps observed in a structurally aligned protein pair database
      suggests a simple gap penalty function.
AB  - Gap penalty is an important component of the scoring scheme that is needed when
      searching for homologous proteins and for accurate alignment of protein
      sequences. Most homology search and sequence alignment algorithms employ a
      heuristic 'affine gap penalty' scheme q + r x n, in which q is the penalty for
      opening a gap, r the penalty for extending it and n the gap length. In order to
      devise a more rational scoring scheme, we examined the pattern of gaps that occur
      in a database of structurally aligned protein domain pairs. We find that the
      logarithm of the frequency of gaps varies linearly with the length of the gap,
      but with a break at a gap of length 3, and is well approximated by two linear
      regression lines with R2 values of 1.0 and 0.99. The bilinear behavior is
      retained when gaps are categorized by secondary structures of the two residues
      flanking the gap. Similar results were obtained when another, totally
      independent, structurally aligned protein pair database was used. These results
      suggest a modification of the affine gap penalty function.

PMID- 15155853
TI  - Structural insights by molecular dynamics simulations into specificity of the
      major human AP endonuclease toward the benzene-derived DNA adduct, pBQ-C.
AB  - The benzetheno exocyclic adduct of the cytosine (C) base (pBQ-C) is a product of
      reaction between DNA and a stable metabolite of the human carcinogen benzene, p
      benzoquinone (pBQ). We reported previously that the pBQ-C-containing duplex is a
      substrate for the human AP endonuclease (APE1), an enzyme that cleaves an
      apurinic/apyrimidinic (AP) site from double stranded DNA. In this work, using
      molecular dynamics simulation (MD), we provided a structural explanation for the
      recognition of the pBQ-C adduct by APE1. Molecular modeling of the DNA duplex
      containing pBQ-C revealed significant displacement of this adduct toward the
      major groove with pronounced kinking of the DNA at the lesion site, which could
      serve as a structural element recognized by the APE1 enzyme. Using 3 ns MD it was
      shown that the position of the pBQ-C adduct is stabilized by two hydrogen bonds
      formed between the adduct and the active site amino acids Asp 189 and Ala 175.
      The pBQ-C/APE1 complex, generated by MD, has a similar hydrogen bond network
      between target phosphodiester bond at the pBQ-C site and key amino acids at the
      active site, as in the crystallographically determined APE1 complexed with an AP
      site-containing DNA duplex. The position of the adduct at the enzyme active site,
      together with the hydrogen bond network, suggests a similar reaction mechanism
      for phosphodiester bond cleavage of oligonucleotide containing pBQ-C as reported
      for the AP site.

PMID- 15155854
TI  - A protein-dependent riboswitch controlling ptsGHI operon expression in Bacillus
      subtilis: RNA structure rather than sequence provides interaction specificity.
AB  - The Gram-positive soil bacterium Bacillus subtilis transports glucose by the
      phosphotransferase system. The genes for this system are encoded in the ptsGHI
      operon. The expression of this operon is controlled at the level of transcript
      elongation by a protein-dependent riboswitch. In the absence of glucose a
      transcriptional terminator prevents elongation into the structural genes. In the
      presence of glucose, the GlcT protein is activated and binds and stabilizes an
      alternative RNA structure that overlaps the terminator and prevents termination.
      In this work, we have studied the structural and sequence requirements for the
      two mutually exclusive RNA structures, the terminator and the RNA antiterminator
      (the RAT sequence). In both cases, the structure seems to be more important than
      the actual sequence. The number of paired and unpaired bases in the RAT sequence
      is essential for recognition by the antiterminator protein GlcT. In contrast,
      mutations of individual bases are well tolerated as long as the general structure
      of the RAT is not impaired. The introduction of one additional base in the RAT
      changed its structure and resulted in complete loss of interaction with GlcT. In
      contrast, this mutant RAT was efficiently recognized by a different B.subtilis
      antitermination protein, LicT.

PMID- 15155855
TI  - Chemically induced increases and decreases in the rate of expansion of a CAG*CTG
      triplet repeat.
AB  - Somatic mosaicism of repeat length is prominent in repeat expansion disorders
      such as Huntington disease and myotonic dystrophy. Somatic mosaicism is age
      dependent, tissue-specific and expansion-biased, and likely contributes toward
      the tissue-specificity and progressive nature of the symptoms. We propose that
      therapies targeted at somatic repeat expansion may have general utility in these
      disorders. Specifically, suppression of somatic expansion would be expected to be
      therapeutic, whilst reversion of the expanded mutant repeat to within the normal
      range would be predicted to be curative. However, the effects of genotoxic agents
      on the mutational properties of specific nuclear genes are notoriously difficult
      to define. Nonetheless, we have determined that chronic exposure over a three
      month period to a number of genotoxic agents can alter the rate of triplet repeat
      expansion in whole populations of mammalian cells. Interestingly, high doses of
      caffeine increased the rate of expansion by approximately 60%. More importantly,
      cytosine arabinoside, ethidium bromide, 5-azacytidine and aspirin all
      significantly reduced the rate of expansion by from 35 to 75%. These data
      establish that drug induced suppression of somatic expansion is possible. These
      data also suggest that highly unstable expanded simple sequence repeats may act
      as sensitive reporters of genotoxic assault in the soma.

PMID- 15155856
TI  - Microfluidic device reads up to four consecutive base pairs in DNA sequencing-by
      synthesis.
AB  - We have developed the first fully integrated microfluidic system for DNA
      sequencing-by-synthesis. Using this chip and fluorescence detection, we have
      reliably sequenced up to 4 consecutive bps. The described sequencer can be
      integrated with other microfluidic components on the same chip to produce true
      lab-on-a-chip technology. The surface chemistry that was designed to anchor the
      DNA to elastomeric microchannels is useful in a broad range of studies and
      applications.

PMID- 15155857
TI  - The RmInt1 group II intron has two different retrohoming pathways for mobility
      using predominantly the nascent lagging strand at DNA replication forks for
      priming.
AB  - Sinorhizobium meliloti RmInt1 is an efficient mobile group II intron that uses an
      unknown reverse transcriptase priming mechanism as the intron ribonucleoprotein
      complex can reverse splice into DNA target substrates but cannot carry out site
      specific second strand cleavage due to the lack of a C-terminal DNA endonuclease
      domain. We show here that, like other mobile group II introns, RmInt1 moves
      around by an efficient RNA-based retrohoming mechanism. We found evidence of two
      distinct RmInt1 retrohoming pathways for mobility depending on the orientation of
      the target site relative to the direction of DNA replication. The preferred
      retrohoming pathway is consistent with reverse splicing of the intron RNA into
      single-stranded DNA at a replication fork, using a nascent lagging DNA strand as
      the primer for reverse transcription. This strand bias is the opposite of that
      reported for mobility of the lactococcal Ll.ltrB intron in the absence of second
      strand cleavage. The mobility mechanism found here for RmInt1 may be used for
      dissemination by many bacterial group II introns encoding proteins lacking the
      DNA endonuclease domain.

PMID- 15155858
TI  - Identification of sparsely distributed clusters of cis-regulatory elements in
      sets of co-expressed genes.
AB  - Sequence information and high-throughput methods to measure gene expression
      levels open the door to explore transcriptional regulation using computational
      tools. Combinatorial regulation and sparseness of regulatory elements throughout
      the genome allow organisms to control the spatial and temporal patterns of gene
      expression. Here we study the organization of cis-regulatory elements in sets of
      co-regulated genes. We build an algorithm to search for combinations of
      transcription factor binding sites that are enriched in a set of potentially co
      regulated genes with respect to the whole genome. No knowledge is assumed about
      involvement of specific sets of transcription factors. Instead, the search is
      exhaustively conducted over combinations of up to four binding sites obtained
      from databases or motif search algorithms. We evaluate the performance on random
      sets of genes as a negative control and on three biologically validated sets of
      co-regulated genes in yeasts, flies and humans. We show that we can detect DNA
      regions that play a role in the control of transcription. These results shed
      light on the structure of transcription regulatory regions in eukaryotes and can
      be directly applied to clusters of co-expressed genes obtained in gene expression
      studies. Supplementary information is available at http://www.mit.edu/
      approximately kreiman/resources/cisregul/.

PMID- 15155859
TI  - Clamping down on weak terminal base pairs: oligonucleotides with molecular caps
      as fidelity-enhancing elements at the 5'- and 3'-terminal residues.
AB  - The base-pairing fidelity of oligonucleotides depends on the identity of the
      nucleobases involved and the position of matched or mismatched base pairs in the
      duplex. Nucleobases forming weak base pairs, as well as a terminal position favor
      mispairing. We have searched for 5'-appended acylamido caps that enhance the
      stability and base-pairing fidelity of oligonucleotides with a 5'-terminal 2'
      deoxyadenosine residue using combinatorial synthesis and MALDI-monitored nuclease
      selections. This provided the residue of 4-(pyren-1-yl)butyric acid as a lead.
      Lead optimization gave (S)-N-(pyren-1-ylmethyl)pyrrolidine-3-phosphate as a cap
      that increases duplex stability and base-pairing fidelity. For the duplex of 5'
      AGGTTGAC-3' with its fully complementary target, this cap gives an increase in
      the UV melting point T(m) of +10.9 degrees C. The T(m) is 6.3-8.3 degrees C lower
      when a mismatched nucleobase faces the 5'-terminal dA residue. The optimized cap
      can be introduced via automated DNA synthesis. It was combined with an
      anthraquinone carboxylic acid residue as a cap for the 3'-terminal residue. A
      doubly capped dodecamer thus prepared gives a melting point decrease for double
      terminal mismatches that is 5.7-5.9 degrees C greater than that for the
      unmodified control duplex.

PMID- 15155861
TI  - Use of isolated populations in the study of a human obesity syndrome, the Bardet
      Biedl syndrome.
AB  - Bardet-Biedl syndrome (BBS) is a pleiotropic genetic disorder with the cardinal
      features of obesity, photoreceptor degeneration, polydactyly, hypogenitalism,
      renal abnormalities, and developmental delay. Other associated clinical findings
      in BBS patients include diabetes, hypertension, and congenital heart defects. The
      clinical diagnosis is based on the presence of at least four of the cardinal
      symptoms. BBS is recognized to be a genetically heterogeneous autosomal recessive
      disorder mapping to eight known loci. Positional cloning and candidate gene
      evaluation have resulted in the identification of six BBS genes. Mutation of one
      of these genes, BBS6, also causes McKusick-Kaufman syndrome. The BBS6 gene is
      predicted to code for a protein with sequence similarity to the chaperonin family
      of proteins. The predicted BBS1, BBS2, BBS4, BBS7, and BBS8 gene products do not
      seem to be molecular chaperones, on the basis of a lack of sequence similarity to
      the chaperonin family of proteins. The identification of BBS8 suggests a possible
      role in cilia function for BBS gene products. It remains to be determined whether
      the multiple BBS proteins are part of a multisubunit complex or do not directly
      interact with each other but are part of a common pathway. The study of BBS
      illustrates the value of using isolated inbred populations for the study of human
      genetic diseases and suggests strategies for facilitating the study of complex
      diseases and traits.

PMID- 15155862
TI  - Vitamin A activation of transforming growth factor-beta1 enhances porcine ileum
      wound healing in vitro.
AB  - Treatment with transforming growth factor-beta(1) (TGF-beta(1)) has been shown to
      be effective in accelerating skin wound healing. Another approach to gain the
      beneficial effects of TGF-beta(1) on wound healing could be the activation of
      tissue stores of latent TGF-beta(1) with agents such as vitamin A. The aims of
      this study were to determine whether 1) vitamin A is effective in enhancing
      intestinal wound healing in vitro and 2) activation of TGF-beta(1) is increased
      during wound healing with vitamin A treatment. We used the intraluminal chemical
      induction model of necrotizing enterocolitis (NEC), which was adapted to the 1-wk
      old piglet. Injured (NEC) and noninjured full-thickness ileum explants harvested
      from the piglets were cultured for 24 and 48 h in serum-free medium supplemented
      with all-trans retinol (ATR; 0, 2, 5, and 10 microM). All concentrations of ATR
      improved recovery of normal ileal wall cytoarchitecture of NEC explants, with
      maximal recovery observed with 2 microM ATR after 24 h of culture. Further
      recovery after 48 h was observed with 5 and 10 microM ATR but did not achieve the
      degree of healing observed with 2 microM ATR. There were no observable adverse
      effects of ATR on noninjured ileal explant morphology. Active TGF-beta(1) was
      identified only in the NEC explants incubated with ATR. The results of this study
      demonstrate that administration of vitamin A accelerates recovery of normal
      intestinal wall cytoarchitecture of injured ileum in vitro, without adversely
      affecting noninjured ileum. The increased activation of latent TGF-beta(1) may,
      in part, be responsible for the accelerated healing of injured ileum observed
      with vitamin A administration.

PMID- 15155863
TI  - Whole-body leucine kinetics and the acute phase response during acute infection
      in marasmic Malawian children.
AB  - This study compared leucine kinetics and acute-phase protein and cytokine
      concentrations in three groups of Malawian children who were fed an isoenergetic,
      isonitrogenous diet: children with marasmus with (n = 25) and without (n = 17)
      infection and well-nourished children with infection (n =13). The hypotheses
      tested were that whole-body leucine kinetics will be less in marasmic acutely
      infected children than in well-nourished acutely infected children but greater
      than in marasmic uninfected children. Children were studied after 24 h of therapy
      using standard (13)C-leucine stable isotope tracer techniques. Well-nourished
      children with acute infection had greater leucine kinetic rates than did marasmic
      children with acute infection; nonoxidative leucine disposal was 153 +/- 31
      versus 118 +/- 43 micromol leucine. kg(-1). h(-1), leucine derived from whole
      body proteolysis was 196 +/- 34 versus 121 +/- 47, and leucine oxidation was 85
      +/- 31 versus 45 +/- 13 (p < 0.01 for all comparisons). Leucine kinetic rates
      were similar in marasmic children with and without acute infection. Well
      nourished children with acute infection increased their serum concentration of
      five of six acute-phase proteins during the first 24 h, whereas marasmic children
      with infection did not have any increases. The serum concentrations of IL-6 were
      elevated in well-nourished and marasmic children with infection. These data
      suggest that the cytokine stimulus for the acute-phase protein kinetic response
      to acute infection is present in marasmic children but that the acute-phase
      protein metabolic response is blunted by malnutrition.

PMID- 15155864
TI  - Role of virus-induced myocardial affections in sudden infant death syndrome: a
      prospective postmortem study.
AB  - The cause of sudden infant death syndrome (SIDS) is an unresolved problem of high
      relevance. Previous studies indicate a role of infections. In our prospective
      study, we investigated the frequency of virus-induced myocardial affections in
      SIDS. Postmortem samples from SIDS victims and control subjects were investigated
      prospectively. Pediatric cases of unnatural death served as controls. Samples
      were studied for enteroviruses, adenoviruses, parvovirus B19, and Epstein-Barr
      virus applying PCR. Immunohistochemical investigations for inflammatory cells,
      the necrosis marker C5b-9((m)) complement complex, and the enteroviral capsid
      protein VP1 were performed. Overall, 62 SIDS victims were studied. As controls,
      11 infants were enrolled. Enteroviruses were detected in 14 (22.5%), adenoviruses
      in 2 (3.2%), Epstein-Barr viruses in 3 (4.8%), and parvovirus B19 in 7 (11.2%)
      cases of SIDS. Control group samples were completely virus negative. Compared
      with controls, immunohistochemical investigations partially revealed a
      significant increase in the number of T lymphocytes in SIDS myocardial samples (p
      < 0.05). Furthermore, cases with elevated numbers of leukocytes and macrophages,
      microfocal C5b-9((m))(+) necroses, and enteroviral VP1 capsid protein within the
      myocardium were detected. Applying a comprehensive combination of molecular and
      immunohistochemical techniques, our results demonstrate a clearly higher
      prevalence of viral myocardial affections in SIDS. Our results emphasize the
      importance of PCR-based diagnosis of viral myocardial affections. We suggest
      preliminary criteria for cellular immunohistochemical diagnosis of viral
      myocardial affections derived from our findings. For future investigations in
      SIDS, we suggest a comprehensive approach that includes PCR and
      immunohistochemistry. Our results offer novel strategies for diagnosis of
      pediatric myocardial viral affections.

PMID- 15155860
TI  - Activation of cryptic 3' splice sites within introns of cellular genes following
      gene entrapment.
AB  - Gene trap vectors developed for genome-wide mutagenesis can be used to study
      factors governing the expression of exons inserted throughout the genome. For
      example, entrapment vectors consisting of a partial 3'-terminal exon [i.e. a
      neomycin resistance gene (Neo), a poly(A) site, but no 3' splice site] were
      typically expressed following insertion into introns, from cellular transcripts
      that spliced to cryptic 3' splice sites present either within the targeting
      vector or in the adjacent intron. A vector (U3NeoSV1) containing the wild-type
      Neo sequence preferentially disrupted genes that spliced in-frame to a cryptic 3'
      splice site in the Neo coding sequence and expressed functional neomycin
      phosphotransferase fusion proteins. Removal of the cryptic Neo 3' splice site did
      not reduce the proportion of clones with inserts in introns; rather, the fusion
      transcripts utilized cryptic 3' splice sites present in the adjacent intron or
      generated by virus integration. However, gene entrapment with U3NeoSV2 was
      considerably more random than with U3NeoSV1, consistent with the widespread
      occurrence of potential 3' splice site sequences in the introns of cellular
      genes. These results clarify the mechanisms of gene entrapment by U3 gene trap
      vectors and illustrate features of exon definition required for 3' processing and
      polyadenylation of cellular transcripts.

PMID- 15155865
TI  - Defective neutrophil oxidative burst in preterm newborns on exposure to coagulase
      negative staphylococci.
AB  - The neutrophil oxidative burst is a product of the regulated assembly of the
      multicomponent oxidase enzyme. Our aim was to compare the oxidative burst in term
      (n = 10) and preterm newborns <31 wk gestational age (n = 10) after stimulation
      with coagulase-negative staphylococci in vitro. Strains of Streptococcus
      epidermidis with different invasive and slime-producing properties, one strain of
      S. haemolyticus, and one strain of group B-streptococcus were investigated. A
      whole-blood flow cytometric assay using the oxidation of hydroethidine to
      ethidium bromide was used. The oxidative activity in unstimulated neutrophil
      granulocytes [polymorphonuclear leukocytes (PMNLs)] was similar in term and
      preterm newborns, but the preterm newborns showed a significantly lower capacity
      to up-regulate the oxidative burst intensity after bacterial stimulation (p =
      0.004). In the term but not in the preterm group, the oxidative burst intensity
      after bacterial stimulation correlated with the baseline oxidative burst
      intensity. After bacterial stimulation, there was a trend toward a greater
      percentage of activated neutrophils in the term group than in the preterm group,
      but the difference was less pronounced than that in oxidative burst intensity.
      Significant differences in oxidative burst response to different bacterial
      strains were observed (p < 0.001), but the differences could not be correlated
      exclusively to invasive capacity or slime-producing properties. It is concluded
      that the baseline oxidative activity is similar in term and preterm PMNLs but
      that preterm PMNLs have a decreased capacity to increase the oxidative burst in
      response to bacterial stimulation.

PMID- 15155866
TI  - L-lysine decreases nitric oxide production and increases vascular resistance in
      lungs isolated from lipopolysaccharide-treated neonatal pigs.
AB  - Nitric oxide (NO) production may depend on the uptake of L-arginine (L-arg), the
      substrate for NO synthase in inflammatory lung diseases. The cellular transport
      of L-arg occurs via the cationic amino acid transporters (CAT), and L-lysine (L
      lys) competitively inhibits CAT. Neonatal pigs were treated with
      lipopolysaccharide (LPS) or vehicle for 4 h. LPS increased exhaled NO (exNO;
      0.026 +/- 0.003 to 0.046 +/- 0.003 nmol. kg(-1). min(-1); p < 0.005) and
      decreased mean systemic arterial blood pressure (89 +/- 4 to 67 +/- 4 mm Hg; p <
      0.05), whereas vehicle did not affect exNO or mean systemic arterial blood
      pressure. The lungs were then isolated and perfused; exNO was greater in lungs
      from LPS-treated animals (0.08 +/- 0.01 nmol/kg/min) than in lungs from vehicle
      treated animals (0.05 +/- 0.01 nmol. kg(-1). min(-1); p < 0.05). The addition of
      L-arg (0.3 mM) significantly (p < 0.05) increased exNO production in both groups
      of lungs (mean increase 0.04 +/- 0.01 nmol. kg(-1). min(-1) LPS-treated lungs, p
      < 0.05; mean increase 0.02 +/- 0.01 nmol. kg(-1). min(-1) vehicle-treated lungs);
      however, L-arg decreased pulmonary vascular resistance (PVR) only in LPS-treated
      lungs (mean decrease 0.03 +/- 0.01 mm Hg. ml(-1). kg(-1). min(-1), p < 0.05). L
      lys caused a dose-dependent decrease in exNO production and a dose-dependent
      increase in PVR in LPS-treated lungs. L-lys decreased exNO only at 30 mM and had
      no effect on PVR in vehicle-treated lungs. In four lungs each from vehicle- and
      LPS-treated animals, reverse transcriptase-PCR demonstrated CAT-2 mRNA only in
      LPS-treated animals. These results suggest that the increased NO production in
      the lungs from LPS-treated animals depends on the uptake of vascular L-arg.

PMID- 15155867
TI  - Reduced respiratory control with ADP and changed pattern of respiratory chain
      enzymes as a result of selective deficiency of the mitochondrial ATP synthase.
AB  - The F(o)F(1)-ATPase, a multisubunit protein complex of the inner mitochondrial
      membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as
      a result of a dysfunction of ATPase can be caused by mutations in mitochondrial
      DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin.
      Here we present a detailed functional and immunochemical analysis of a new case
      of selective and generalized ATPase deficiency found in an Austrian patient. The
      defect manifested with developmental delay, muscle hypotonia, failure to thrive,
      ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal
      period. A low-degree dilated cardiomyopathy of the left ventricle developed
      between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase
      activity and an 86% decrease in the content of the ATPase complex was found in
      muscle mitochondria. It was associated with a significant decrease of ADP
      stimulated respiration of succinate (1.5-fold) and respiratory control with ADP
      (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the
      respiratory chain complex I and compensatory increase in the content of complexes
      III and IV. The same ATPase deficiency without an increase in respiratory chain
      complexes was found in fibroblasts, suggesting a generalized defect with tissue
      specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8
      genes indicates a nuclear origin of the defect.

PMID- 15155868
TI  - Osteoprotegerin in human milk: a potential role in the regulation of bone
      metabolism and immune development.
AB  - Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily. It is
      a soluble "decoy" receptor for tumor necrosis factor-related apoptosis-inducing
      ligand and ligand of the receptor activator of NF-kappaB. As such, OPG inhibits
      osteoclast activity and regulates the immune system. Human milk is a complex
      biologic fluid that supplies nutritional and protective factors to the breast-fed
      infant. In the present study, human milk samples at various times postpartum were
      assessed for the presence of OPG. Using biochemical as well as immunologic and
      biologic techniques we showed that human milk contains OPG at a level that is
      1000-fold higher than that found in normal human serum. We observed that human
      breast milk cells and the human mammary epithelial cell line MCF-7 express OPG,
      indicating that both cell types are possible sources of milk OPG in vivo. In
      vitro studies demonstrated that milk OPG is biologically active and suggested
      that it may contribute to the antiresorptive activity of milk on bone, as well as
      tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of T
      cell proliferation. OPG-like activity was also observed in bovine colostrum and
      milk. Furthermore, we were able to detect human OPG in the sera of rats gavaged
      with human milk. We discuss the relevance of our findings for the breast-fed
      infant and for the prevention of immune and bone disorders.

PMID- 15155869
TI  - Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid
      compartments are associated with adverse pulmonary and neurologic outcomes in
      preterm infants.
AB  - Recent evidence strongly implicates the inflammatory response to intrauterine
      infection in the pathogenesis of neonatal brain and lung injury. We hypothesized
      that lung and brain injury in preterm infants occurs during a common
      developmental window of vulnerability as the result of an inflammatory response
      in different compartments. To determine whether inflammatory markers in these
      compartments are associated with bronchopulmonary dysplasia (BPD) or cranial
      ultrasound (CUS) abnormalities in infants <33 wk gestation age (GA) and <1501 g
      birth weight, we analyzed placental pathology and serum and cerebrospinal fluid
      (CSF) IL-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations
      in 276 infants. Logistic regressions were performed stratified by GA. Histologic
      chorioamnionitis was significantly associated with BPD in infants </=28 wk GA (OR
      3.6, p = 0.027). Maternal stage of chorioamnionitis significantly correlated with
      severity of BPD. Presence of a fetal inflammatory response indicated by fetal
      vasculitis or elevated cytokines was not associated with the development of BPD.
      Serum IL-6 >/=17 pg/mL was associated with an abnormal CUS in infants >28 wk GA
      (OR 3.36, p = 0.023) but not </=28 wk GA. CSF concentrations of IL-6 >/=6.5 pg/mL
      and TNF-alpha >/=3 pg/mL were associated with abnormal CUS in infants </=28 wk GA
      (IL-6 OR 3.0; TNF-alpha OR 3.5; p < 0.05 each case) but not >/=28 wk GA. These
      data suggest that in infants </=28 wks GA, BPD may be initiated by inflammatory
      mediators in amniotic fluid, but brain injury may involve variations in the
      systemic inflammatory response.

PMID- 15155870
TI  - Prognostic significance of amplitude-integrated EEG during the first 72 hours
      after birth in severely asphyxiated neonates.
AB  - Amplitude-integrated EEG (aEEG) is used to select patients for neuroprotective
      therapy after perinatal asphyxia because of its prognostic accuracy within
      several hours after birth. We aimed to determine the natural course of aEEG
      patterns during the first 72 h of life, in relation to neurologic outcome, in a
      group of severely asphyxiated term infants. Thirty infants, admitted to our
      neonatal intensive care unit from October 1998 until February 2001, were studied
      retrospectively. The aEEG traces obtained during the first 72 h after birth were
      assessed by pattern recognition: continuous normal voltage (CNV), discontinuous
      normal voltage (DNV), burst suppression (BS), continuous low voltage, and flat
      trace. Epileptic activity was also determined. The course of aEEG patterns was
      examined in relation to neurologic findings at 24 mo. Initially, 17 of 30 infants
      had severely abnormal aEEG patterns (BS or worse), which changed spontaneously to
      normal voltage patterns (CNV, DNV) in 7 within 48 h. The sooner the abnormalities
      on aEEG disappeared, the better the prognosis. The likelihood ratio of BS or
      worse for adverse outcome was 2.7 (95% confidence interval 1.4-5.0) between 0 and
      6 h and increased to a highest value of 19 (95% confidence interval 2.8-128)
      between 24 and 36 h; after 48 h, it was not significant. Normal voltage patterns
      (CNV and DNV) up to 48 h of life were predictive for normal neurologic outcomes
      (negative likelihood ratios <0.3). Our findings indicate that the course of aEEG
      patterns adds to the prognostic value of aEEG monitoring in asphyxiated infants.
      Spontaneous recovery of severely abnormal aEEG patterns is not uncommon.

PMID- 15155871
TI  - Iron deficiency alters auditory recognition memory in newborn infants of diabetic
      mothers.
AB  - Infants of diabetic mothers (IDMs) are at risk for perinatal brain iron
      deficiency that may target the developing hippocampus. The objective of this
      study was to evaluate hippocampally based recognition memory and infant
      development in IDMs with suspected brain iron deficiency (BID; cord ferritin
      </=34 microg/L) compared with IDMs with sufficient brain iron stores (BIS; cord
      ferritin >34 microg/L) using event-related potentials (ERPs). ERPs assessed
      neonatal auditory cortical responses to sounds and auditory recognition memory in
      response to the mother's voice compared with a stranger's voice. Thirty-two
      newborn IDMs had cord serum ferritin concentrations and provided neonatal ERP
      data (n = 23) and/or blinded 1 y developmental assessments (n = 28). Auditory
      cortical responses to speech and nonspeech sounds were similar in the BID and BIS
      groups. In the maternal voice recognition paradigm, peak latencies were shorter
      in the BID group than in the BIS group. Infants in the BIS group displayed a
      significant negative slow wave for the strangers' voices compared with the
      mothers' voices, whereas the BID group did not. Higher cord ferritin
      concentrations were correlated with larger negative slow waves at the right
      temporal (T4) electrode site. At 1 y of age, motor development was slower in the
      BID group than in the BIS group. IDMs suspected to have BID demonstrated impaired
      neonatal auditory recognition memory and lower psychomotor developmental scores
      at 1 y of age than IDMs with BIS. These impairments map onto areas of the
      developing brain known to be vulnerable to iron deficiency.

PMID- 15155872
TI  - Megakaryocyte growth and development factor is a potent growth factor for
      primitive hematopoietic progenitors in the human fetus.
AB  - Megakaryocyte growth and development factor (MGDF), or thrombopoietin, has
      received considerable attention as a therapeutic agent for treating
      thrombocytopenia or for its use in the ex vivo culture of hematopoietic stem
      cells. MGDF is known to support the growth of a broad spectrum of hematopoietic
      precursors obtained from adult or neonatal tissues, but its effects on the growth
      of fetal progenitors and stem cells has not been studied. Human CD38(+)CD34(2+)
      progenitors and CD38(-)CD34(2+) cells, a population that contains stem cells,
      were isolated from midgestation liver and grown under defined conditions with
      MGDF and various cytokines known to support the growth of primitive hematopoietic
      precursors. In clonal assays of colony-forming cells (CFCs), MGDF supported the
      growth of 15-25% of candidate stem cells when combined with granulocyte colony
      stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF),
      flk-2/flt3 ligand, or stem cell factor. MGDF was observed to strongly support the
      early stages of hematopoiesis and expansion of high proliferative potential CFCs.
      More mature progenitors were expanded nearly 78-fold in 1 wk of culture with
      MGDF+SCF+GM-CSF. MGDF alone was also found to support the short-term (2 d)
      survival of CD38(-)CD34(2+) high proliferative potential CFCs. The effects of
      MGDF were more modest on CD38(+)CD34(2+) progenitors with only additive increases
      in colony formation being observed. These findings suggest that MGDF
      administration in fetuses and neonates may strongly affect the growth and
      mobilization of primitive hematopoietic progenitors and that MGDF may find use in
      the ex vivo growth and expansion of fetal stem cells.

PMID- 15155874
TI  - Glucosinolate and amino acid biosynthesis in Arabidopsis.
AB  - Enzymes that catalyze the condensation of acetyl coenzyme A and 2-oxo acids are
      likely to be important in two distinct metabolic pathways in Arabidopsis. These
      are the synthesis of isopropylmalate, an intermediate of Leu biosynthesis in
      primary metabolism, and the synthesis of methylthioalkylmalates, intermediates of
      Met elongation in the synthesis of aliphatic glucosinolates (GSLs), in secondary
      metabolism. Four Arabidopsis genes in the ecotype Columbia potentially encode
      proteins that could catalyze these reactions. MAM1 and MAML are adjacent genes on
      chromosome 5 at the Gsl-elong locus, while MAML-3 and MAML-4 are at opposite ends
      of chr 1. The isopropylmalate synthase activity of each member of the MAM-like
      gene family was investigated by heterologous expression in an isopropylmalate
      synthase-null Escherichia coli mutant. Only the expression of MAML-3 restored the
      ability of the mutant to grow in the absence of Leu. A MAML knockout line (KO)
      lacked long-chain aliphatic GSLs, which were restored when the KO was transformed
      with a functional MAML gene. Variation in expression of MAML did not alter the
      total levels of Met-derived GSLs, but just the ratio of chain lengths. MAML
      overexpression in Columbia led to an increase in long-chain GSLs, and an increase
      in 3C GSLs. Moreover, plants overexpressing MAML contained at least two novel
      amino acids. One of these was positively identified via MS/MS as homo-Leu, while
      the other, with identical mass and fragmentation patterns, was likely to be homo
      Ile. A MAML-4 KO did not exhibit any changes in GSL profile, but had perturbed
      soluble amino acid content.

PMID- 15155873
TI  - Arabidopsis downy mildew resistance gene RPP27 encodes a receptor-like protein
      similar to CLAVATA2 and tomato Cf-9.
AB  - The Arabidopsis Ler-RPP27 gene confers AtSgt1b-independent resistance to downy
      mildew (Peronospora parasitica) isolate Hiks1. The RPP27 locus was mapped to a
      four-bacterial artificial chromosome interval on chromosome 1 from genetic
      analysis of a cross between the enhanced susceptibility mutant Col-edm1 (Col
      sgt1) and Landsberg erecta (Ler-0). A Cf-like candidate gene in this interval was
      PCR amplified from Ler-0 and transformed into mutant Col-rpp7.1 plants.
      Homozygous transgenic lines conferred resistance to Hiks1 and at least four Ler-0
      avirulent/Columbia-0 (Col-0) virulent isolates of downy mildew pathogen. A full
      length RPP27 cDNA was isolated, and analysis of the deduced amino acid sequences
      showed that the gene encodes a receptor-like protein (RLP) with a distinct domain
      structure, composed of a signal peptide followed by extracellular Leu-rich
      repeats, a membrane spanning region, and a short cytoplasmic carboxyl domain.
      RPP27 is the first RLP-encoding gene to be implicated in disease resistance in
      Arabidopsis, enabling the deployment of Arabidopsis techniques to investigate the
      mechanisms of RLP function. Homology searches of the Arabidopsis genome, using
      the RPP27, Cf-9, and Cf-2 protein sequences as a starting point, identify 59
      RLPs, including the already known CLAVATA2 and TOO MANY MOUTHS genes. A
      combination of sequence and phylogenetic analysis of these predicted RLPs reveals
      conserved structural features of the family.

PMID- 15155876
TI  - TILLING. Traditional mutagenesis meets functional genomics.
AB  - Most of the genes of an organism are known from sequence, but most of the
      phenotypes are obscure. Thus, reverse genetics has become an important goal for
      many biologists. However, reverse-genetic methodologies are not similarly
      applicable to all organisms. In the general strategy for reverse genetics that we
      call TILLING (for Targeting Induced Local Lesions in Genomes), traditional
      chemical mutagenesis is followed by high-throughput screening for point
      mutations. TILLING promises to be generally applicable. Furthermore, because
      TILLING does not involve transgenic modifications, it is attractive not only for
      functional genomics but also for agricultural applications. Here, we present an
      overview of the status of TILLING methodology, including Ecotilling, which
      entails detection of natural variation. We describe public TILLING efforts in
      Arabidopsis and other organisms, including maize (Zea mays) and zebrafish. We
      conclude that TILLING, a technology developed in plants, is rapidly being adopted
      in other systems.

PMID- 15155875
TI  - A family of auxin-conjugate hydrolases that contributes to free indole-3-acetic
      acid levels during Arabidopsis germination.
AB  - Auxins are hormones important for numerous processes throughout plant growth and
      development. Plants use several mechanisms to regulate levels of the auxin indole
      3-acetic acid (IAA), including the formation and hydrolysis of amide-linked
      conjugates that act as storage or inactivation forms of the hormone. Certain
      members of an Arabidopsis amidohydrolase family hydrolyze these conjugates to
      free IAA in vitro. We examined amidohydrolase gene expression using northern and
      promoter-beta-glucuronidase analyses and found overlapping but distinct patterns
      of expression. To examine the in vivo importance of auxin-conjugate hydrolysis,
      we generated a triple hydrolase mutant, ilr1 iar3 ill2, which is deficient in
      three of these hydrolases. We compared root and hypocotyl growth of the single,
      double, and triple hydrolase mutants on IAA-Ala, IAA-Leu, and IAA-Phe. The
      hydrolase mutant phenotypic profiles on different conjugates reveal the in vivo
      activities and relative importance of ILR1, IAR3, and ILL2 in IAA-conjugate
      hydrolysis. In addition to defective responses to exogenous conjugates, ilr1 iar3
      ill2 roots are slightly less responsive to exogenous IAA. The triple mutant also
      has a shorter hypocotyl and fewer lateral roots than wild type on unsupplemented
      medium. As suggested by the mutant phenotypes, ilr1 iar3 ill2 imbibed seeds and
      seedlings have lower IAA levels than wild type and accumulate IAA-Ala and IAA
      Leu, conjugates that are substrates of the absent hydrolases. These results
      indicate that amidohydrolases contribute free IAA to the auxin pool during
      germination in Arabidopsis.

PMID- 15155877
TI  - The receptor for the fungal elicitor ethylene-inducing xylanase is a member of a
      resistance-like gene family in tomato.
AB  - An ethylene-inducing xylanase (EIX) is a potent elicitor of plant defense
      responses in specific cultivars of tobacco (Nicotiana tabacum) and tomato
      (Lycopersicon esculentum). The LeEix locus in tomatoes was characterized by map
      based cloning, which led to the identification of a novel gene cluster from which
      two members (LeEix1 and LeEix2) were isolated. Similar to the tomato Ve
      resistance genes in tomato plants, the deduced amino acid sequences encoded by
      LeEix1 and LeEix2 contain a Leu zipper, an extracellular Leu-rich repeat domain
      with glycosylation signals, a transmembrane domain, and a C-terminal domain with
      a mammalian endocytosis signal. Silencing expression of the LeEix genes prevented
      the binding of EIX to cells of an EIX-responsive plant and thus inhibited the
      hypersensitive response. Overexpression of either LeEix1 or LeEix2 genes in EIX
      nonresponsive tobacco plants enabled the binding of EIX, although only LeEix2
      could transmit the signal that induced the hypersensitive response.
      Overexpressing LeEix2 in mammalian COS-7 cells enables binding of EIX, indicating
      physical interaction between the EIX elicitor and LeEix2 gene product. Structural
      analysis of the LeEix proteins suggests that they belong to a class of cell
      surface glycoproteins with a signal for receptor-mediated endocytosis. Mutating
      the endocytosis signal in LeEix2 (Tyr 993 to Ala) abolished its ability to induce
      the hypersensitive response, suggesting that endocytosis plays a key role in the
      signal transduction pathway.

PMID- 15155878
TI  - The Arabidopsis Rab GTPase RabA4b localizes to the tips of growing root hair
      cells.
AB  - Spatial and temporal control of cell wall deposition plays a unique and critical
      role during growth and development in plants. To characterize membrane
      trafficking pathways involved in these processes, we have examined the function
      of a plant Rab GTPase, RabA4b, during polarized expansion in developing root hair
      cells. Whereas a small fraction of RabA4b cofractionated with Golgi membrane
      marker proteins, the majority of this protein labeled a unique membrane
      compartment that did not cofractionate with the previously characterized trans
      Golgi network syntaxin proteins SYP41 and SYP51. An enhanced yellow fluorescent
      protein (EYFP)-RabA4b fusion protein specifically localizes to the tips of
      growing root hair cells in Arabidopsis thaliana. Tip-localized EYFP-RabA4b
      disappears in mature root hair cells that have stopped expanding, and polar
      localization of the EYFP-RabA4b is disrupted by latrunculin B treatment. Loss of
      tip localization of EYFP-RabA4b was correlated with inhibition of expansion; upon
      washout of the inhibitor, root hair expansion recovered only after tip
      localization of the EYFP-RabA4b compartments was reestablished. Furthermore, in
      mutants with defective root hair morphology, EYFP-RabA4b was improperly localized
      or was absent from the tips of root hair cells. We propose that RabA4b regulates
      membrane trafficking through a compartment involved in the polarized secretion of
      cell wall components in plant cells.

PMID- 15155879
TI  - Constitutive photomorphogenesis 1 and multiple photoreceptors control degradation
      of phytochrome interacting factor 3, a transcription factor required for light
      signaling in Arabidopsis.
AB  - Light, in a quality- and quantity-dependent fashion, induces nuclear import of
      the plant photoreceptors phytochrome, promotes interaction of phytochrome A
      (phyA) and phyB with transcription factors including phytochrome interacting
      factor 3 (PIF3), and is thought to trigger a transcriptional cascade to regulate
      the expression of approximately 2500 genes in Arabidopsis thaliana. Here, we show
      that controlled degradation of the transcription factor PIF3 is a major
      regulatory step in light signaling. We demonstrate that accumulation of PIF3 in
      the nucleus in dark requires constitutive photomorphogenesis 1 (COP1), a negative
      regulator of photomorphogenesis, and show that red (R) and far-red light (FR)
      induce rapid degradation of the PIF3 protein. This process is controlled by the
      concerted action of the R/FR absorbing phyA, phyB, and phyD photoreceptors, and
      it is not affected by COP1. Rapid light-induced degradation of PIF3 indicates
      that interaction of PIF3 with these phytochrome species is transient. In
      addition, we provide evidence that the poc1 mutant, a postulated PIF3
      overexpressor that displays hypersensitivity to R but not to FR, lacks detectable
      amounts of the PIF3 protein. Thus, we propose that PIF3 acts transiently, and its
      major function is to mediate phytochrome-induced signaling during the
      developmental switch from skotomorphogenesis to photomorphogenesis and/or dark to
      light transitions.

PMID- 15155880
TI  - Histidine kinase homologs that act as cytokinin receptors possess overlapping
      functions in the regulation of shoot and root growth in Arabidopsis.
AB  - Cytokinins are plant hormones that may play essential and crucial roles in
      various aspects of plant growth and development. Although the functional
      significance of exogenous cytokinins as to the proliferation and differentiation
      of cells has been well documented, the biological roles of endogenous cytokinins
      have remained largely unknown. The recent discovery of the Arabidopsis Histidine
      Kinase 4 (AHK4)/CRE1/WOL cytokinin receptor in Arabidopsis thaliana strongly
      suggested that the cellular response to cytokinins involves a two-component
      signal transduction system. However, the lack of an apparent phenotype in the
      mutant, presumably because of genetic redundancy, prevented us from determining
      the in planta roles of the cytokinin receptor. To gain insight into the molecular
      functions of the three AHK genes AHK2, AHK3, and AHK4 in this study, we
      identified mutational alleles of the AHK2 and AHK3 genes, both of which encode
      sensor histidine kinases closely related to AHK4, and constructed a set of
      multiple ahk mutants. Application of exogenous cytokinins to the resultant
      strains revealed that both AHK2 and AHK3 function as positive regulators for
      cytokinin signaling similar to AHK4. The ahk2 ahk4 and ahk3 ahk4 double mutants
      and the ahk single mutants grew normally, whereas the ahk2 ahk3 double mutants
      exhibited a semidwarf phenotype as to shoots, such as a reduced leaf size and a
      reduced influorescence stem length. The growth and development of the ahk2 ahk3
      ahk4 triple mutant were markedly inhibited in various tissues and organs,
      including the roots and leaves in the vegetative growth phase and the
      influorescence meristem in the reproductive phase. We showed that the inhibition
      of growth is associated with reduced meristematic activity of cells. Expression
      analysis involving AHK:beta-glucuronidase fusion genes suggested that the AHK
      genes are expressed ubiquitously in various tissues during postembryonic growth
      and development. Our results thus strongly suggest that the primary functions of
      AHK genes, and those of endogenous cytokinins, are triggering of the cell
      division and maintenance of the meristematic competence of cells to prevent
      subsequent differentiation until a sufficient number of cells has accumulated
      during organogenesis.

PMID- 15155881
TI  - The Arabidopsis F-box protein SLEEPY1 targets gibberellin signaling repressors
      for gibberellin-induced degradation.
AB  - The nuclear DELLA proteins are highly conserved repressors of hormone gibberellin
      (GA) signaling in plants. In Arabidopsis thaliana, GA derepresses its signaling
      pathway by inducing proteolysis of the DELLA protein REPRESSOR OF ga1-3 (RGA).
      SLEEPY1 (SLY1) encodes an F-box-containing protein, and the loss-of-function sly1
      mutant has a GA-insensitive dwarf phenotype and accumulates a high level of RGA.
      These findings suggested that SLY1 recruits RGA to the SCFSLY1 E3 ligase complex
      for ubiquitination and subsequent degradation by the 26S proteasome. In this
      report, we provide new insight into the molecular mechanism of how SLY1 interacts
      with the DELLA proteins for controlling GA response. By yeast two-hybrid and in
      vitro pull-down assays, we demonstrated that SLY1 interacts directly with RGA and
      GA INSENSITIVE (GAI, a closely related DELLA protein) via their C-terminal GRAS
      domain. The rga and gai null mutations additively suppressed the recessive sly1
      mutant phenotype, further supporting the model that SCFSLY1 targets both RGA and
      GAI for degradation. The N-terminal DELLA domain of RGA previously was shown to
      be essential for GA-induced degradation. However, we found that this DELLA domain
      is not required for protein-protein interaction with SLY1 in yeast (Saccharomyces
      cerevisiae), suggesting that its role is in a GA-triggered conformational change
      of the DELLA proteins. We also identified a novel gain-of-function sly1-d
      mutation that increased GA signaling by reducing the levels of the DELLA protein
      in plants. This effect of sly1-d appears to be caused by an enhanced interaction
      between sly1-d and the DELLA proteins.

PMID- 15155882
TI  - Woronin body function in Magnaporthe grisea is essential for efficient
      pathogenesis and for survival during nitrogen starvation stress.
AB  - The Woronin body is a peroxisome-derived dense-core vesicle that is specific to
      several genera of filamentous ascomycetes, where it has been shown to seal septal
      pores in response to cellular damage. The Hexagonal peroxisome (Hex1) protein was
      recently identified as a major constituent of the Woronin body and shown to be
      responsible for self-assembly of the dense core of this organelle. Using a
      mutation in the Magnaporthe grisea HEX1 ortholog, we define a dual and essential
      function for Woronin bodies during the pathogenic phase of the rice blast fungus.
      We show that the Woronin body is initially required for proper development and
      function of appressoria (infection structures) and subsequently necessary for
      survival of infectious fungal hyphae during invasive growth and host
      colonization. Fungal mycelia lacking HEX1 function were unable to survive
      nitrogen starvation in vitro, suggesting that in planta growth defects are a
      consequence of the mutant's inability to cope with nutritional stress. Thus,
      Woronin body function provides the blast fungus with an important defense against
      the antagonistic and nutrient-limiting environment encountered within the host
      plant.

PMID- 15155883
TI  - The Arabidopsis sku6/spiral1 gene encodes a plus end-localized microtubule
      interacting protein involved in directional cell expansion.
AB  - The sku6-1 mutant of Arabidopsis thaliana exhibits altered patterns of root and
      organ growth. sku6 roots, etiolated hypocotyls, and leaf petioles exhibit right
      handed axial twisting, and root growth on inclined agar media is strongly right
      skewed. The touch-dependent sku6 root skewing phenotype is suppressed by the
      antimicrotubule drugs propyzamide and oryzalin, and right skewing is exacerbated
      by cold treatment. Cloning revealed that sku6-1 is allelic to spiral1-1 (spr1-1).
      However, modifiers in the Columbia (Col) and Landsberg erecta (Ler) ecotype
      backgrounds mask noncomplementation in sku6-1 (Col)/spr1-1 (Ler) F1 plants. The
      SPR1 gene encodes a plant-specific 12-kD protein that is ubiquitously expressed
      and belongs to a six-member gene family in Arabidopsis. An SPR1:green fluorescent
      protein (GFP) fusion expressed in transgenic seedlings localized to microtubules
      within the cortical array, preprophase band, phragmoplast, and mitotic spindle.
      SPR1:GFP was concentrated at the growing ends of cortical microtubules and was
      dependent on polymer growth state; the microtubule-related fluorescence
      dissipated upon polymer shortening. The protein has a repeated motif at both
      ends, separated by a predicted rod-like domain, suggesting that it may act as an
      intermolecular linker. These observations suggest that SPR1 is involved in
      microtubule polymerization dynamics and/or guidance, which in turn influences
      touch-induced directional cell expansion and axial twisting.

PMID- 15155884
TI  - Ectopic expression of the petunia MADS box gene UNSHAVEN accelerates flowering
      and confers leaf-like characteristics to floral organs in a dominant-negative
      manner.
AB  - Several genes belonging to the MADS box transcription factor family have been
      shown to be involved in the transition from vegetative to reproductive growth.
      The Petunia hybrida MADS box gene UNSHAVEN (UNS) shares sequence similarity with
      the Arabidopsis thaliana flowering gene SUPPRESSOR OF OVEREXPRESSION OF
      CONSTANS1, is expressed in vegetative tissues, and is downregulated upon floral
      initiation and the formation of floral meristems. To understand the role of UNS
      in the flowering process, knockout mutants were identified and UNS was expressed
      ectopically in petunia and Arabidopsis. No phenotype was observed in petunia
      plants in which UNS was disrupted by transposon insertion, indicating that its
      function is redundant. Constitutive expression of UNS leads to an acceleration of
      flowering and to the unshaven floral phenotype, which is characterized by ectopic
      trichome formation on floral organs and conversion of petals into organs with
      leaf-like features. The same floral phenotype, accompanied by a delay in
      flowering, was obtained when a truncated version of UNS, lacking the MADS box
      domain, was introduced. We demonstrated that the truncated protein is not
      translocated to the nucleus. Using the overexpression approach with both the full
      length and the nonfunctional truncated UNS protein, we could distinguish between
      phenotypic alterations because of a dominant-negative action of the protein and
      because of its native function in promoting floral transition.

PMID- 15155885
TI  - SPINDLY and GIGANTEA interact and act in Arabidopsis thaliana pathways involved
      in light responses, flowering, and rhythms in cotyledon movements.
AB  - SPINDLY (SPY) is a negative regulator of gibberellin signaling in Arabidopsis
      thaliana that also functions in previously undefined pathways. The N terminus of
      SPY contains a protein-protein interaction domain consisting of 10
      tetratricopeptide repeats (TPRs). GIGANTEA (GI) was recovered from a yeast two
      hybrid screen for proteins that interact with the TPR domain. GI and SPY also
      interacted in Escherichia coli and in vitro pull-down assays. The phenotypes of
      spy and spy-4 gi-2 plants support the hypothesis that SPY functions with GI in
      pathways controlling flowering, circadian cotyledon movements, and hypocotyl
      elongation. GI acts in the long-day flowering pathway upstream of CONSTANS (CO)
      and FLOWERING LOCUS T (FT). Loss of GI function causes late flowering and reduces
      CO and FT RNA levels. Consistent with SPY functioning in the long-day flowering
      pathway upstream of CO, spy-4 partially suppressed the reduced abundance of CO
      and FT RNA and the late flowering of gi-2 plants. Like gi, spy affects the free
      running period of cotyledon movements. The free-running period was lengthened in
      spy-4 mutants and shortened in plants that overexpress SPY under the control of
      the 35S promoter of Cauliflower mosaic virus. When grown under red light, gi-2
      plants have a long hypocotyl. This hypocotyl phenotype was suppressed in spy-4 gi
      2 double mutants. Additionally, dark-grown and far-red-light-grown spy-4
      seedlings were found to have short and long hypocotyls, respectively. The
      different hypocotyl length phenotypes of spy-4 seedlings grown under different
      light conditions are consistent with SPY acting in the GA pathway to inhibit
      hypocotyl elongation and also acting as a light-regulated promoter of elongation.

PMID- 15155887
TI  - A fungal metallothionein is required for pathogenicity of Magnaporthe grisea.
AB  - The causal agent of rice blast disease, the ascomycete fungus Magnaporthe grisea,
      infects rice (Oryza sativa) plants by means of specialized infection structures
      called appressoria, which are formed on the leaf surface and mechanically rupture
      the cuticle. We have identified a gene, Magnaporthe metallothionein 1 (MMT1),
      which is highly expressed throughout growth and development by M. grisea and
      encodes an unusual 22-amino acid metallothionein-like protein containing only six
      Cys residues. The MMT1-encoded protein shows a very high affinity for zinc and
      can act as a powerful antioxidant. Targeted gene disruption of MMT1 produced
      mutants that show accelerated hyphal growth rates and poor sporulation but had no
      effect on metal tolerance. Mmt1 mutants are incapable of causing plant disease
      because of an inability to bring about appressorium-mediated cuticle penetration.
      Mmt1 appears to be distributed in the inner side of the cell wall of the fungus.
      These findings indicate that Mmt1-like metallothioneins may play a novel role in
      fungal cell wall biochemistry that is required for fungal virulence.

PMID- 15155886
TI  - Vitamin E is essential for seed longevity and for preventing lipid peroxidation
      during germination.
AB  - Tocopherols (vitamin E) are lipophilic antioxidants synthesized by all plants and
      are particularly abundant in seeds. Despite cloning of the complete suite of
      tocopherol biosynthetic enzymes and successful engineering of the tocopherol
      content and composition of Arabidopsis thaliana leaves and seeds, the functions
      of tocopherols in plants have remained elusive. To address this issue, we have
      isolated and characterized two VITAMIN E loci (VTE1 and VTE2) in Arabidopsis that
      when mutated result in tocopherol deficiency in all tissues. vte1 disrupts
      tocopherol cyclase activity and accumulates a redox-active biosynthetic
      intermediate, whereas vte2 disrupts homogentisate phytyl transferase activity and
      does not accumulate pathway intermediates. Mutations at either locus cause
      significantly reduced seed longevity compared with the wild type, indicating a
      critical role for tocopherols in maintaining viability during quiescence.
      However, only vte2 mutants exhibited severe seedling growth defects during
      germination and contained levels of lipid hydroperoxides and hydroxy fatty acids
      elevated up to 4- and 100-fold, respectively, relative to the wild type. These
      data demonstrate that a primary function of tocopherols in plants is to limit
      nonenzymatic lipid oxidation during seed storage, germination, and early seedling
      development. The vte mutant phenotypes also explain the strong selection for
      retention of tocopherol biosynthesis during the evolution of seed-bearing plants.

PMID- 15155888
TI  - The novel Myb transcription factor LCR1 regulates the CO2-responsive gene Cah1,
      encoding a periplasmic carbonic anhydrase in Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii acclimates to CO2-limiting stress by inducing a set of
      genes for a carbon-concentrating mechanism (CCM). This set includes the gene
      Cah1, which encodes a periplasmic carbonic anhydrase. Although physiological
      aspects of CO2response have been extensively studied, regulatory components, such
      as transcription factors involved in the acclimation, have not been well
      described in eukaryotic microalgae. Using an arylsulfatase gene driven by the
      Cah1 promoter, a regulatory mutant of Cah1 was isolated and named lcr1 (for low
      CO2 stress response). The photosynthetic affinity for inorganic carbon of lcr1
      was reduced compared with that of wild-type cells. Expression of three low-CO2
      inducible genes, Cah1, Lci1, and Lci6, were regulated by LCR1 as shown by cDNA
      array and RNA gel blot analyses. The Lcr1 gene encodes a protein of 602 amino
      acids containing a single Myb domain, which binds to the Cah1-promoter region.
      Expression of Lcr1 was induced by lowering CO2 levels and controlled by the
      regulatory factor CCM1. These results suggest that LCR1 transmits the low CO2
      signal to at least three CO2-responsive genes and then fully induces CCM.

PMID- 15155889
TI  - NAI1 gene encodes a basic-helix-loop-helix-type putative transcription factor
      that regulates the formation of an endoplasmic reticulum-derived structure, the
      ER body.
AB  - Plant cells develop various types of endoplasmic reticulum (ER)-derived
      structures with specific functions. ER body, an ER-derived compartment in
      Arabidopsis thaliana, is a spindle-shaped structure. The NAI1 gene regulates the
      development of ER bodies because mutation of NAI1 abolishes the formation of ER
      bodies. To better understand the role of NAI1, we cloned the NAI1 gene using a
      positional cloning strategy. The nai1-1 mutant had a single nucleotide change at
      an intron acceptor site of At2g22770 (NAI1 gene). Because of this mutation,
      aberrant splicing of NAI1 mRNA occurs in the nai1-1 mutant. NAI1 encodes a
      transcription factor that has a basic-helix-loop-helix (bHLH) domain. Transient
      expression of NAI1 induced ER bodies in the nai1-1 mutant. Two-dimensional
      electrophoresis and RT-PCR analyses showed that a putative lectin was depressed
      at both the mRNA and protein levels in nai1 mutants, as was a beta-glucosidase
      (PYK10). Our results provide direct evidence that a bHLH protein plays a role in
      the formation of ER bodies.

PMID- 15155890
TI  - Repression of AGAMOUS by BELLRINGER in floral and inflorescence meristems.
AB  - A common aspect of gene regulation in all developmental systems is the sustained
      repression of key regulatory genes in inappropriate spatial or temporal domains.
      To understand the mechanism of transcriptional repression of the floral homeotic
      gene AGAMOUS (AG), we identified two mutations in the BELLRINGER (BLR) gene based
      on a striking floral phenotype, in which homeotic transformations from sepals to
      carpels are found in flowers derived from old terminating shoots. Furthermore,
      this phenotype is drastically enhanced by growth at a high temperature and by
      combining blr with mutants of LEUNIG and SEUSS, two putative transcriptional
      corepressors of AG. We showed that the floral phenotype of blr mutants is caused
      by derepression of AG, suggesting that BLR functions as a transcription
      repressor. Because BLR encodes a BELL1-like (BELL) homeobox protein, direct
      binding of BLR to AG cis-regulatory elements was tested by gel-shift assays, and
      putative BLR binding motifs were identified. In addition, these putative BLR
      binding motifs were shown to be conserved in 17 of the 29 Brassicaceae species by
      phylogenetic footprinting. Because BELL homeobox proteins are a family of plant
      specific transcription factors with 12 members in Arabidopsis thaliana, our
      findings will facilitate the identification of regulatory targets of other BELL
      proteins and help determine their biological functions. The age-dependent and
      high temperature-enhanced derepression of AG in blr mutants led us to propose
      that AG expression might be regulated by a thermal time-dependent molecular
      mechanism.

PMID- 15155891
TI  - CENTRIN2 modulates homologous recombination and nucleotide excision repair in
      Arabidopsis.
AB  - A genetic screen of a population of Arabidopsis thaliana lines exhibiting
      enhanced somatic homologous recombination yielded a mutant affected in expression
      of a gene encoding a caltractin-like protein (centrin). The hyperrecombinogenic
      phenotype could be reproduced using RNA interference (RNAi) technology. Both the
      original mutant and the RNAi plants exhibited a moderate UV-C sensitivity as well
      as a reduced efficiency of in vitro repair of UV-damaged DNA. Transcription
      profiling of the mutant showed that expression of components of the nucleotide
      excision repair (NER) pathway and of factors involved in other DNA repair
      processes were significantly changed. Our data suggest an indirect involvement of
      centrin in recombinational DNA repair via the modulation of the NER pathway.
      These findings thus point to a novel interconnection between an early step of NER
      and homologous recombination, which may play a critical role in plant DNA repair.

PMID- 15155893
TI  - Screen-film mammography versus full-field digital mammography with soft-copy
      reading: randomized trial in a population-based screening program--the Oslo II
      Study.
AB  - PURPOSE: To prospectively compare cancer detection rates, recall rates, and
      positive predictive values at screen-film mammography (SFM) with those at full
      field digital mammography (FFDM) with soft-copy reading in a population-based
      screening program in Norway. MATERIALS AND METHODS: Of 43,429 women invited,
      25,263 women aged 45-69 years attended the screening program and were randomized,
      with adjustments for age and area of residence, to undergo SFM or FFDM. Two
      standard views of each breast were acquired. Independent double reading was
      performed with use of a five-point rating scale for probability of cancer. Recall
      rates, positive predictive values, and cancer detection rates were compared for
      two age groups (45-49 and 50-69 years) by using the chi(2) test. RESULTS:
      Overall, 73 cancers in 17,911 women were detected at SFM (detection rate, 0.41%),
      compared with 41 cancers in 6,997 women at FFDM (detection rate, 0.59%; P =.06).
      In the group aged 50-69 years, 56 cancers in 10,304 women were detected at SFM
      (detection rate, 0.54%), compared with 33 cancers in 3,985 at FFDM (detection
      rate, 0.83%); the difference in cancer detection rates approached significance (P
      =.053). In the group aged 45-49 years, 17 cancers in 7,607 women were detected at
      SFM (detection rate, 0.22%), compared with eight cancers in 3,012 at FFDM
      (detection rate, 0.27%). Recall rates in both age groups were significantly
      higher at FFDM than at SFM (P <.05), but positive predictive value was not
      significantly different. CONCLUSION: FFDM allowed a higher cancer detection rate
      than did SFM in the group aged 50-69, although the difference did not reach
      statistical significance. The detection rate was nearly equal for the two
      modalities in the group aged 45-49. SFM and FFDM with soft-copy reading are
      comparable techniques for population-based screening mammography programs.

PMID- 15155894
TI  - Acute appendicitis: comparison of low-dose and standard-dose unenhanced multi
      detector row CT.
AB  - PURPOSE: To prospectively compare low- and standard-dose unenhanced multi
      detector row computed tomography (CT) in patients suspected of having acute
      appendicitis. MATERIALS AND METHODS: Ninety-five consecutive patients underwent
      two unenhanced multi-detector row CT examinations with 4 x 2.5-mm collimation,
      120 kVp, and 30 and 100 effective mAs. Two radiologists independently read the
      images obtained at each dose during two sessions. Readers recorded visualization
      of the appendix and presence of gas in its lumen, appendicolith, periappendiceal
      fat stranding, cecal wall thickening, and abscess or phlegmon to measure the
      diameter of the appendix and to propose diagnosis (appendicitis or alternative).
      Data were compared according to dose and reader, with definite diagnosis
      established on basis of surgical findings (n = 37) or clinical follow-up. chi(2)
      tests and logistic regression were used. Measurement agreements were assessed
      with Cohen kappa statistics. RESULTS: Twenty-nine patients had a definite
      diagnosis of appendicitis. No difference was observed between the frequency of
      visualization of the appendix (P =.874) neither in its mean diameter (P =.101
      .696, according to readers and sessions) nor in the readers' overall diagnosis (P
      =.788) at each dose. Sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of each sign were not different between
      doses. Fat stranding, appendicolith, and diameter were the most predictive signs,
      regardless of dose, yielding approximately 90% of correct diagnoses. The ability
      to propose a correct alternative diagnosis was not influenced by the dose.
      CONCLUSION: Low-dose unenhanced multi-detector row CT has similar diagnostic
      performance as standard-dose unenhanced multi-detector row CT for the diagnosis
      of acute appendicitis.

PMID- 15155895
TI  - Transhepatic catheter access for hemodialysis.
AB  - PURPOSE: To retrospectively review the authors' experience regarding the safety
      and functionality of transhepatic hemodialysis catheters. MATERIALS AND METHODS:
      Sixteen patients (seven men and nine women aged 21-77 years; mean age, 51.6
      years) underwent placement of 21 transhepatic hemodialysis catheters.
      Transhepatic catheters were placed in the absence of an available peripheral
      venous site (11 patients) or for preservation of a single remaining venous site
      to achieve permanent vascular access. Safety was assessed by means of
      complications encountered, and catheter functionality was assessed by means of
      total access site service interval. Catheter patency was described by using a
      Kaplan-Meier survival curve, and number of catheter days were compared according
      to patient sex by using a two-sample t test. RESULTS: Technical success was
      achieved in all patients. The mean total access site service interval was 138
      catheter days (range, 0-599 days), and there was no significant difference
      according to patient sex (P =.869). Of the 16 catheters placed initially, five
      became dislodged and required an additional access procedure to be performed.
      These 21 catheters required 30 exchanges in 10 patients (48%) (range, 1-6
      exchanges per patient). The most common reason for catheter exchange was device
      failure. There were six complications among 21 catheters placed (29%), including
      one death from massive intraperitoneal hemorrhage on the day after catheter
      placement. CONCLUSION: Transhepatic hemodialysis catheters offer a viable option
      to patients with limited options; however, there are maintenance issues and
      complications.

PMID- 15155892
TI  - The Arabidopsis putative G protein-coupled receptor GCR1 interacts with the G
      protein alpha subunit GPA1 and regulates abscisic acid signaling.
AB  - Heterotrimeric G proteins composed of alpha, beta, and gamma subunits link ligand
      perception by G protein-coupled receptors (GPCRs) with downstream effectors,
      providing a ubiquitous signaling mechanism in eukaryotes. The Arabidopsis
      thaliana genome encodes single prototypical Galpha (GPA1) and Gbeta (AGB1)
      subunits, and two probable Ggamma subunits (AGG1 and AGG2). One Arabidopsis gene,
      GCR1, encodes a protein with significant sequence similarity to nonplant GPCRs
      and a predicted 7-transmembrane domain structure characteristic of GPCRs.
      However, whether GCR1 actually interacts with GPA1 was unknown. We demonstrate by
      in vitro pull-down assays, by yeast split-ubiquitin assays, and by
      coimmunoprecipitation from plant tissue that GCR1 and GPA1 are indeed physically
      coupled. GCR1-GPA1 interaction depends on intracellular domains of GCR1. gcr1 T
      DNA insertional mutants exhibit hypersensitivity to abscisic acid (ABA) in assays
      of root growth, gene regulation, and stomatal response. gcr1 guard cells are also
      hypersensitive to the lipid metabolite, sphingosine-1-phosphate (S1P), which is a
      transducer of the ABA signal upstream of GPA1. Because gpa1 mutants exhibit
      insensitivity in aspects of guard cell ABA and S1P responses, whereas gcr1
      mutants exhibit hypersensitivity, GCR1 may act as a negative regulator of GPA1
      mediated ABA responses in guard cells.

PMID- 15155896
TI  - Cerebrospinal fluid flow in foramen magnum: temporal and spatial patterns at MR
      imaging in volunteers and in patients with Chiari I malformation.
AB  - PURPOSE: To measure spatial and temporal variations in cerebrospinal fluid (CSF)
      flow through the cardiac cycle and throughout the subarachnoid space at magnetic
      resonance (MR) imaging in volunteer subjects with no known neurologic or spinal
      problems and in patients with Chiari I malformation. MATERIALS AND METHODS: A
      cardiac-gated phase-contrast MR technique was used to acquire images at 14 time
      points evenly spaced through the cardiac cycle in 10 volunteers and eight
      patients with Chiari I malformation. Instantaneous CSF velocities were displayed
      as temporal and spatial plots and examined for homogeneity, differences between
      flow anterior and flow posterior to the spinal cord, synchronous bidirectional
      flow, and equivalence of the caudad flow and craniad flow in each voxel. Indexes
      for flow homogeneity, synchronous bidirectional flow, and preferential flow
      direction were calculated, and differences between the patient and volunteer
      groups were tested for significance with a t test of the means. RESULTS: In
      volunteers, diastolic velocity peaked in two regions in the anterior paramedial
      subarachnoid space. Patients had greater inhomogeneity of flow than volunteers.
      They had substantially increased flow (jets) in the anterior paramedial
      locations. Synchronous bidirectional flow was seen in six of the patients and in
      none of the volunteers. Cephalad flow in the jets or nodes (P =.05), proportion
      of cephalad and caudad flow in the anterior compartment (P <.005 for both), and
      the fraction of voxels with flow directionality (P =.03) differed significantly
      between patients and volunteers. CONCLUSION: CSF flow in symptomatic patients
      with Chiari I malformation, unlike that in volunteer subjects, is characterized
      by flow jets, regions with a preponderance of flow in one direction, and
      synchronous bidirectional flow.

PMID- 15155897
TI  - Carpal tunnel syndrome: diagnostic usefulness of sonography.
AB  - PURPOSE: To prospectively evaluate accuracy of sonography for diagnosis of carpal
      tunnel syndrome (CTS) in patients clinically suspected of having the disease in
      one or both hands. MATERIALS AND METHODS: A prospective cohort of 133 patients
      suspected of having CTS were referred to a teaching hospital between October 2001
      and June 2002 for electrodiagnostic study. One hundred twenty patients (98 women,
      22 men; mean age, 49 years; range, 19-83 years) underwent sonography within 1
      week after electrodiagnostic study. Radiologist was blinded to electrodiagnostic
      study results. Seventy-five patients had bilateral symptoms; 23 patients, right
      hand symptoms; and 22 patients, left-hand symptoms (total, 195 symptomatic
      hands). Cross-sectional area of median nerve was measured at three levels:
      immediately proximal to carpal tunnel inlet, at carpal tunnel inlet, and at
      carpal tunnel outlet. Flexor retinaculum was used as a landmark to margins of
      carpal tunnel. Optimal threshold levels (determined with classification and
      regression tree analysis) for areas proximal to and at tunnel inlet and at tunnel
      outlet were used to discriminate between patients with and patients without
      disease. Sensitivity, specificity, and false-positive and false-negative rates
      were derived on the basis of final diagnosis, which was determined with clinical
      history and electrodiagnostic study results as reference standard. RESULTS: For
      right hands, sonography had sensitivity of 94% (66 of 70); specificity, 65% (17
      of 26); false-positive rate, 12% (nine of 75); and false-negative rate, 19% (four
      of 21) (cutoff, 0.09 cm(2) proximal to tunnel inlet and 0.12 cm(2) at tunnel
      outlet). For left hands, sensitivity was 83% (53 of 64); specificity, 73% (24 of
      33); false-positive rate, 15% (nine of 62); and false-negative rate, 31% (11 of
      35) (cutoff, 0.10 cm(2) proximal to tunnel inlet). CONCLUSION: Sonography is
      comparable to electrodiagnostic study in diagnosis of CTS and should be
      considered as initial test of choice for patients suspected of having CTS.

PMID- 15155898
TI  - Thyroid tissue: US-guided percutaneous laser thermal ablation.
AB  - PURPOSE: To evaluate in vivo the safety and effectiveness of percutaneous laser
      thermal ablation (LTA) in the debulking of thyroid lesions. MATERIALS AND
      METHODS: Twenty-five adult patients at poor surgical risk with cold nodules (n =
      8), autonomously hyperfunctioning thyroid nodules (n = 16), or anaplastic
      carcinoma (n = 1) underwent LTA. One to four 21-gauge spinal needles were
      inserted with ultrasonographic (US) guidance into the thyroid lesions. A 300
      microm-diameter quartz optical fiber was advanced through the sheath of the
      needle. Nd:YAG laser was used with output power of 3-5 W. Side effects,
      complications, and clinical and hormonal changes were evaluated at the end of LTA
      and during follow-up. Linear regression analysis was used to investigate the
      correlation between energy delivered and reduction in nodule volume. Volume of
      induced necrosis and reduction in nodule volume were assessed with US or computed
      tomography. RESULTS: LTA was performed without difficulties in 76 LTA sessions.
      After treatment with 5 W, two patients experienced mild dysphonia, which resolved
      after 48 hours and 2 months. Improvement of local compression symptoms was
      experienced by 12 of 14 (86%) patients. Thyroid-stimulating hormone (TSH) was
      detectable in five of 16 (31%) patients with hyperfunctioning nodules at 6 months
      after LTA. Volume of induced necrosis ranged from 0.8 to 3.9 mL per session.
      Anaplastic carcinoma treated with four fibers yielded 32.0 mL of necrosis. Echo
      structure and baseline volume did not influence response. Energy load and
      reduction in nodule volume were significantly correlated (r(2) =.75, P <.001).
      Mean nodule volume reduction at 6 months in hyperfunctioning nodules was 3.3 mL
      +/- 2.8 (62% +/- 21.4 [SD]) and in cold nodules was 7.7 mL +/- 7.5 (63% +/-
      13.8). CONCLUSION: LTA may be a therapeutic tool for highly selected problems in
      the treatment of thyroid lesions.

PMID- 15155900
TI  - Magnetic tests for magnetosome chains in Martian meteorite ALH84001.
AB  - Transmission electron microscopy studies have been used to argue that magnetite
      crystals in carbonate from Martian meteorite ALH84001 have a composition and
      morphology indistinguishable from that of magnetotactic bacteria. It has even
      been claimed from scanning electron microscopy imaging that some ALH84001
      magnetite crystals are aligned in chains. Alignment of magnetosomes in chains is
      perhaps the most distinctive of the six crystallographic properties thought to be
      collectively unique to magnetofossils. Here we use three rock magnetic
      techniques, low-temperature cycling, the Moskowitz test, and ferromagnetic
      resonance, to sense the bulk composition and crystallography of millions of
      ALH84001 magnetite crystals. The magnetic data demonstrate that although the
      magnetite is unusually pure and fine-grained in a manner similar to terrestrial
      magnetofossils, most or all of the crystals are not arranged in chains.

PMID- 15155899
TI  - Modeling first-hit functions of the t(12;21) TEL-AML1 translocation in mice.
AB  - The t(12;21) translocation, which generates the TEL-AML1 (ETV6-RUNX1) fusion
      gene, is the most common structural chromosome change in childhood cancer and is
      exclusively associated with the common B cell precursor subset of acute
      lymphoblastic leukemia (ALL). Evidence suggests that the translocation usually
      occurs in utero during fetal hemopoiesis and most probably constitutes an
      initiating or first-hit mutation that is necessary but insufficient for the
      development of overt, clinical leukemia. The mechanism by which TEL-AML1
      contributes to this early stage of leukemogenesis is unknown. To address this
      question we have analyzed hemopoiesis in mice syngeneically transplanted with TEL
      AML1-transduced bone marrow stem cells. TEL-AML1 expression was associated with
      an accumulation/expansion of primitive c-kit-positive multipotent progenitors and
      a modest increase in myeloid colony-forming cells. TEL-AML1 expression was,
      however, permissive for myeloid differentiation. Analysis of B lymphopoiesis
      revealed an increase in early, pro-B cells but a differentiation deficit beyond
      that stage, resulting in reduced B cell production in the marrow. TEL-AML1
      positive B cell progenitors exhibited reduced expression of the surrogate light
      chain component lambda5 and the IL-7 receptor, both of which may contribute to
      impedance of differentiation in vivo and account for their reduced in vitro
      clonogenicity in IL-7. A selective differentiation deficit of B lineage
      progenitors (i) is consistent with the phenotype of TEL-AML1-associated leukemia
      in children and (ii) provides a potential mechanism for the protracted
      preleukemic state that often precedes ALL. These results provide mechanistic
      insight into the role of the t(12;21) translocation in the initiation of common B
      cell precursor ALL.

PMID- 15155901
TI  - Gene expression alterations over large chromosomal regions in cancers include
      multiple genes unrelated to malignant progression.
AB  - In solid tumors, the relationship between DNA copy number and global expression
      over large chromosomal regions has not been systematically explored. We used a
      12,626-gene expression array analysis of head and neck squamous cell carcinoma
      and normal oral mucosa and annotated gene expression levels to specific
      chromosomal loci. Expression alterations correlated with reported data using
      comparative genomic hybridization. When genes with significant differences in
      expression between normal and malignant lesions, as defined by significance
      analysis of microarrays (SAM), were compared to nonsignificant genes, similar
      chromosomal patterns of alteration in expression were noted. Individual tumors
      underwent microsatellite analysis and chi(2) analysis of expression at 3p and
      22q. Significant 3p underexpression and 22q overexpression were found in all
      primary tumors with 3p and 22q allelic imbalance, respectively, whereas no tumor
      without allelic imbalance on these chromosomal arms demonstrated expression
      differences. Loss and gain of chromosomal material in solid cancers can alter
      gene expression over large chromosomal regions, including multiple genes
      unrelated to malignant progression.

PMID- 15155902
TI  - Structure of membrane-bound alpha-synuclein studied by site-directed spin
      labeling.
AB  - Many of the proposed physiological functions of alpha-synuclein, a protein
      involved in the pathogenesis of Parkinson's disease, are related to its ability
      to interact with phospholipids. To better understand the conformational changes
      that occur upon membrane binding of monomeric alpha-synuclein, we performed EPR
      analysis of 47 singly labeled alpha-synuclein derivatives. We show that membrane
      interaction is mediated by major conformational changes within seven N-terminal
      11-aa repeats, which reorganize from a highly dynamic structure into an elongated
      helical structure devoid of significant tertiary packing. Furthermore, we find
      that analogous positions from different repeats are in equivalent locations with
      respect to membrane proximity. These and other findings suggest a curved membrane
      dependent alpha-helical structure, wherein each 11-aa repeat takes up three
      helical turns. Similar helical structures could also apply to apolipoproteins and
      other lipid-interacting proteins with related 11-aa repeats.

PMID- 15155903
TI  - Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in
      Sandhoff disease mice.
AB  - Sandhoff disease is a prototypical lysosomal storage disorder in which a
      heritable deficiency of a lysosomal enzyme, beta-hexosaminidase, results in the
      storage of the enzyme's substrates in lysosomes. As with many of the other
      lysosomal storage diseases, neurodegeneration is a prominent feature. Although
      the cellular and molecular pathways that underlie the neurodegenerative process
      are not yet fully understood, macrophage/microglial-mediated inflammation has
      been suggested as one possible mechanism. We now show that the expanded
      macrophage/microglial population in the CNS of Sandhoff disease mice is
      compounded by the infiltration of cells from the periphery. Coincident with the
      cellular infiltration was an increased expression of macrophage-inflammatory
      protein 1alpha (MIP-1alpha), a leukocyte chemokine, in astrocytes. Deletion of
      MIP-1alpha expression resulted in a substantial decrease in infiltration and
      macrophage/microglial-associated pathology together with neuronal apoptosis in
      Sandhoff disease mice. These mice without MIP-1alpha showed improved neurologic
      status and a longer lifespan. The results indicate that the pathogenesis of
      Sandhoff disease involves an increase in MIP-1alpha that induces monocytes to
      infiltrate the CNS, expand the activated macrophage/microglial population, and
      trigger apoptosis of neurons, resulting in a rapid neurodegenerative course.

PMID- 15155904
TI  - Molecular sorting by stochastic resonance.
AB  - To sort a targeted species from a mixture, we introduce a procedure that relies
      on the enhancement of its effective diffusion coefficient. We use the formation
      of a host-guest complex between alpha-cyclodextrin and a dye to evidence the dye
      dispersion when the medium is submitted to an oscillating field. In particular,
      we demonstrate that the effective diffusion coefficient of the dye may be
      increased far beyond its intrinsic value by tuning the driving field frequency in
      the stochastic resonance regime. We use this effect to selectively sort from a
      mixture a dye that is addressed by its rate constants for association with alpha
      cyclodextrin.

PMID- 15155905
TI  - Nuclear receptor corepressor RIP140 regulates fat accumulation.
AB  - Nuclear receptors and their coactivators have been shown to function as key
      regulators of adipose tissue biology. Here we show that a ligand-dependent
      transcriptional repressor for nuclear receptors plays a crucial role in
      regulating the balance between energy storage and energy expenditure. Mice devoid
      of the corepressor protein RIP140 are lean, show resistance to high-fat diet
      induced obesity and hepatic steatosis, and have increased oxygen consumption.
      Although the process of adipogenesis is unaffected, expression of certain
      lipogenic enzymes is reduced. In contrast, genes involved in energy dissipation
      and mitochondrial uncoupling, including uncoupling protein 1, are markedly
      increased. Therefore, the maintenance of energy homeostasis requires the action
      of a transcriptional repressor in white adipose tissue, and ligand-dependent
      recruitment of RIP140 to nuclear receptors may provide a therapeutic target in
      the treatment of obesity and related disorders.

PMID- 15155906
TI  - Bipotential mouse embryonic liver stem cell lines contribute to liver
      regeneration and differentiate as bile ducts and hepatocytes.
AB  - Cell lines have many advantages: they can be manipulated genetically, expanded,
      and stockpiled for organ transplantation. Freshly isolated hepatocytes, oval
      cells, pancreatic cells, and hematopoietic stem cells have been shown to
      repopulate the damaged liver. Here we show that bipotential mouse embryonic liver
      (BMEL) stem cell lines participate in liver regeneration in albumin-urokinase
      plasminogen activator/severe combined immunodeficiency disease (Alb-uPA/SCID)
      transgenic mice. In the liver, BMEL-GFP cells proliferate and differentiate into
      both hepatocytes and bile ducts, forming small to large clusters detected
      throughout the 3-8 weeks analyzed after transplantation. Moreover, they respond
      like host cells to signals for growth, differentiation, and even zonal expression
      of metabolic enzymes, showing regulated expression of cytokeratins and liver
      enriched transcription factors. Immunostaining for MHC class I molecules revealed
      that cells do not coexpress donor and recipient H-2 haplotypes, as would be the
      case had cell fusion occurred. This report shows that immortalized stem cell
      lines not only are competent to participate in the repair of a damaged tissue but
      also can differentiate into the two major epithelial cell types of a complex
      organ, hepatocytes and bile ducts.

PMID- 15155907
TI  - Cytokine detection by antibody-based proximity ligation.
AB  - Efficient and precise detection techniques, along with extensive repertoires of
      specific binding reagents, will be needed to meet the challenges of proteome
      analyses. The recently established proximity ligation mechanism enables sensitive
      high-capacity protein measurements by converting the detection of specific
      proteins to the analysis of DNA sequences. Proximity probes containing
      oligonucleotide extensions are designed to bind pairwise to target proteins and
      to form amplifiable tag sequences by ligation when brought in proximity. In our
      previous report, both the ligatable arms and the protein binders were DNA
      molecules. We now generalize the method by providing simple and convenient
      protocols to convert any polyclonal antibodies or matched pair of monoclonal
      antibodies to proximity probe sets through the attachment of oligonucleotide
      sequences. Sufficient reagent for >100,000 proximity ligation assays can be
      prepared from 1 microg of antibody. The technique is applied to measure cytokines
      in a homogenous test format with femtomolar detection sensitivities in 1-microl
      samples, and we exemplify its utility in situations when only minute sample
      amounts are available.

PMID- 15155908
TI  - Molecular diversity of astrocytes with implications for neurological disorders.
AB  - The astrocyte represents the most abundant yet least understood cell type of the
      CNS. Here, we use a stringent experimental strategy to molecularly define the
      astrocyte lineage by integrating microarray datasets across several in vitro
      model systems of astrocyte differentiation, primary astrocyte cultures, and
      various astrocyterich CNS structures. The intersection of astrocyte data sets,
      coupled with the application of nonastrocytic exclusion filters, yielded many
      astrocyte-specific genes possessing strikingly varied patterns of regional CNS
      expression. Annotation of these astrocyte-specific genes provides direct
      molecular documentation of the diverse physiological roles of the astrocyte
      lineage. This global perspective in the normal brain also provides a framework
      for how astrocytes may participate in the pathogenesis of common neurological
      disorders like Alzheimer's disease, Parkinson's disease, stroke, epilepsy, and
      primary brain tumors.

PMID- 15155909
TI  - Evidence for assembly of prions with left-handed beta-helices into trimers.
AB  - Studies using low-resolution fiber diffraction, electron microscopy, and atomic
      force microscopy on various amyloid fibrils indicate that the misfolded
      conformers must be modular, compact, and adopt a cross-beta structure. In an
      earlier study, we used electron crystallography to delineate molecular models of
      the N-terminally truncated, disease-causing isoform (PrP(Sc)) of the prion
      protein, designated PrP 27-30, which polymerizes into amyloid fibrils, but we
      were unable to choose between a trimeric or hexameric arrangement of right- or
      left-handed beta-helical models. From a study of 119 all-beta folds observed in
      globular proteins, we have now determined that, if PrP(Sc) follows a known
      protein fold, it adopts either a beta-sandwich or parallel beta-helical
      architecture. With increasing evidence arguing for a parallel beta-sheet
      organization in amyloids, we contend that the sequence of PrP is compatible with
      a parallel left-handed beta-helical fold. Left-handed beta-helices readily form
      trimers, providing a natural template for a trimeric model of PrP(Sc). This
      trimeric model accommodates the PrP sequence from residues 89-175 in a beta
      helical conformation with the C terminus (residues 176-227), retaining the
      disulfide-linked alpha-helical conformation observed in the normal cellular
      isoform. In addition, the proposed model matches the structural constraints of
      the PrP 27-30 crystals, positioning residues 141-176 and the N-linked sugars
      appropriately. Our parallel left-handed beta-helical model provides a coherent
      framework that is consistent with many structural, biochemical, immunological,
      and propagation features of prions. Moreover, the parallel left-handed beta
      helical model for PrP(Sc) may provide important clues to the structure of
      filaments found in some other neurodegenerative diseases.

PMID- 15155910
TI  - Identification of anthrax toxin genes in a Bacillus cereus associated with an
      illness resembling inhalation anthrax.
AB  - Bacillus anthracis is the etiologic agent of anthrax, an acute fatal disease
      among mammals. It was thought to differ from Bacillus cereus, an opportunistic
      pathogen and cause of food poisoning, by the presence of plasmids pXO1 and pXO2,
      which encode the lethal toxin complex and the poly-gamma-d-glutamic acid capsule,
      respectively. This work describes a non-B. anthracis isolate that possesses the
      anthrax toxin genes and is capable of causing a severe inhalation anthrax-like
      illness. Although initial phenotypic and 16S rRNA analysis identified this
      isolate as B. cereus, the rapid generation and analysis of a high-coverage draft
      genome sequence revealed the presence of a circular plasmid, named pBCXO1, with
      99.6% similarity with the B. anthracis toxin-encoding plasmid, pXO1. Although
      homologues of the pXO2 encoded capsule genes were not found, a polysaccharide
      capsule cluster is encoded on a second, previously unidentified plasmid, pBC218.
      A/J mice challenged with B. cereus G9241 confirmed the virulence of this strain.
      These findings represent an example of how genomics could rapidly assist public
      health experts responding not only to clearly identified select agents but also
      to novel agents with similar pathogenic potentials. In this study, we combined a
      public health approach with genome analysis to provide insight into the
      correlation of phenotypic characteristics and their genetic basis.

PMID- 15155911
TI  - Abrupt tropical vegetation response to rapid climate changes.
AB  - Identifying leads and lags between high- and low-latitude abrupt climate shifts
      is needed to understand where and how such events were triggered. Vascular plant
      biomarkers preserved in Cariaco basin sediments reveal rapid vegetation changes
      in northern South America during the last deglaciation, 15,000 to 10,000 years
      ago. Comparing the biomarker records to climate proxies from the same sediment
      core provides a precise measure of the relative timing of changes in different
      regions. Abrupt deglacial climate shifts in tropical and high-latitude North
      Atlantic regions were synchronous, whereas changes in tropical vegetation
      consistently lagged climate shifts by several decades.

PMID- 15155912
TI  - Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion
      conformers.
AB  - The protein-remodeling factor Hsp104 governs inheritance of [PSI+], a yeast prion
      formed by self-perpetuating amyloid conformers of the translation termination
      factor Sup35. Perplexingly, either excess or insufficient Hsp104 eliminates
      [PSI+]. In vitro, at low concentrations, Hsp104 catalyzed the formation of
      oligomeric intermediates that proved critical for the nucleation of Sup 35
      fibrillization de novo and displayed a conformation common among amyloidogenic
      polypeptides. At higher Hsp104 concentrations, amyloidogenic oligomerization and
      contingent fibrillization were abolished. Hsp104 also disassembled mature fibers
      in a manner that initially exposed new surfaces for conformational replication
      but eventually exterminated prion conformers. These Hsp104 activities differed in
      their reaction mechanism and can explain [PSI+] inheritance patterns.

PMID- 15155913
TI  - Protein kinase G from pathogenic mycobacteria promotes survival within
      macrophages.
AB  - Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages,
      allowing them to survive intracellularly. We found that the eukaryotic-like
      serine/threonine protein kinase G from pathogenic mycobacteria was secreted
      within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating
      intracellular survival of mycobacteria. Inactivation of protein kinase G by gene
      disruption or chemical inhibition resulted in lysosomal localization and
      mycobacterial cell death in infected macrophages. Besides identifying a target
      for the control of mycobacterial infections, these findings suggest that
      pathogenic mycobacteria have evolved eukaryotic-like signal transduction
      mechanisms capable of modulating host cell trafficking pathways.

PMID- 15155914
TI  - Praise, for a change.

PMID- 15155915
TI  - Biotechnology. Monsanto pulls the plug on genetically modified wheat.

PMID- 15155916
TI  - Stem cell research. Zerhouni's answer buoys supporters.

PMID- 15155917
TI  - Biotechnology. A new tack on herbicide resistance.

PMID- 15155918
TI  - Biomedical ethics. House committee slams NIH's plan on consulting.

PMID- 15155919
TI  - Exoplanets. Hotter-than-hot newcomers push the planetary envelope.

PMID- 15155920
TI  - Cosmology. Galaxy clusters bear witness to universal speed-up.

PMID- 15155921
TI  - Genetics. Genome resources to boost canines' role in gene hunts.

PMID- 15155923
TI  - Disease eradication. Two steps forward, one step back in polio fight.

PMID- 15155922
TI  - Number theory. Proof promises progress in prime progressions.

PMID- 15155924
TI  - Archaeology. Iranian dig opens window on new civilization.

PMID- 15155925
TI  - Infectious diseases. One year after outbreak, SARS virus yields some secrets.

PMID- 15155926
TI  - Eastern Europe. Banishing Moldova's demons.

PMID- 15155928
TI  - Physics. Gran Sasso Laboratory sees light at the end of the tunnel.

PMID- 15155927
TI  - Eastern Europe. Transdniestria: scientists left isolated and frustrated.

PMID- 15155929
TI  - Miroslav Radman profile. Bringing biology back to Croatia.

PMID- 15155930
TI  - Marine science. New tools reveal treasures at ocean hot spots.

PMID- 15155931
TI  - Deforestation in Amazonia.

PMID- 15155932
TI  - Painful deception.

PMID- 15155933
TI  - Wisdom in self-scrutiny.

PMID- 15155934
TI  - Bismuth decays.

PMID- 15155935
TI  - Science and industry. Oil: never cry wolf--why the petroleum age is far from
      over.

PMID- 15155936
TI  - Astronomy. The cradle of the solar system.

PMID- 15155937
TI  - Evolution. Insights into innovation.

PMID- 15155938
TI  - Biomedicine. Parkinson's--divergent causes, convergent mechanisms.

PMID- 15155939
TI  - Microbiology. A hitchhiker's guide to type IV secretion.

PMID- 15155941
TI  - Genetic evidence for the demic diffusion of agriculture to India.

PMID- 15155940
TI  - Cell biology. Tickling macrophages, a serious business.

PMID- 15155942
TI  - Optical signatures of the Aharonov-Bohm phase in single-walled carbon nanotubes.
AB  - We report interband magneto-optical spectra for single-walled carbon nanotubes in
      high magnetic fields up to 45 tesla, confirming theoretical predictions that the
      band structure of a single-walled carbon nanotube is dependent on the magnetic
      flux phi threading the tube. We have observed field-induced optical anisotropy as
      well as red shifts and splittings of absorption and photoluminescence peaks. The
      amounts of shifts and splittings depend on the value of phi/phi(0) and are
      quantitatively consistent with theories based on the Aharonov-Bohm effect. These
      results represent evidence of the influence of the Aharonov-Bohm phase on the
      band gap of a solid.

PMID- 15155943
TI  - h/e magnetic flux modulation of the energy gap in nanotube quantum dots.
AB  - We report experiments on quantum dot single-electron-tunneling (SET) transistors
      made from short multiwall nanotubes and threaded by magnetic flux. Such systems
      allow us to probe the electronic energy spectrum of the nanotube and its
      dependence on the magnetic field. Evidence is provided for the interconversion
      between gapped (semiconducting) and ungapped (metallic) states. Our tubes exhibit
      h/e-period magnetic flux dependence, in agreement with simple tight-binding
      calculations.

PMID- 15155944
TI  - Rapid rise of sea level 19,000 years ago and its global implications.
AB  - Evidence from the Irish Sea basin supports the existence of an abrupt rise in sea
      level (meltwater pulse) at 19,000 years before the present (B.P.). Climate
      records indicate a large reduction in the strength of North Atlantic Deep Water
      formation and attendant cooling of the North Atlantic at this time, indicating a
      source of the meltwater pulse from one or more Northern Hemisphere ice sheets.
      Warming of the tropical Atlantic and Pacific oceans and the Southern Hemisphere
      also began at 19,000 years B.P. These responses identify mechanisms responsible
      for the propagation of deglacial climate signals to the Southern Hemisphere and
      tropics while maintaining a cold climate in the Northern Hemisphere.

PMID- 15155945
TI  - Wind as a long-distance dispersal vehicle in the Southern Hemisphere.
AB  - Anisotropic (direction-dependent) long-distance dispersal (LDD) by wind has been
      invoked to explain the strong floristic affinities shared among landmasses in the
      Southern Hemisphere. Its contribution has not yet been systematically tested
      because of the previous lack of global data on winds. We used global winds
      coverage from the National Aeronautics and Space Administration SeaWinds
      scatterometer to test whether floristic similarities of Southern Hemisphere moss,
      liverwort, lichen, and pteridophyte floras conform better with (i) the
      anisotropic LDD hypothesis, which predicts that connection by "wind highways"
      increases floristic similarities, or (ii) a direction-independent LDD hypothesis,
      which predicts that floristic similarities among sites increase with geographic
      proximity. We found a stronger correlation of floristic similarities with wind
      connectivity than with geographic proximities, which supports the idea that wind
      is a dispersal vehicle for many organisms in the Southern Hemisphere.

PMID- 15155946
TI  - Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient
      mice.
AB  - Apoptotic cells expose phosphatidylserine and are swiftly engulfed by
      macrophages. Milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) is
      a protein that binds to apoptotic cells by recognizing phosphatidylserine and
      that enhances the engulfment of apoptotic cells by macrophages. We report that
      tingible body macrophages in the germinal centers of the spleen and lymph nodes
      strongly express MFG-E8. Many apoptotic lymphocytes were found on the MFG-E8-/-
      tingible body macrophages, but they were not efficiently engulfed. The MFG-E8-/-
      mice developed splenomegaly, with the formation of numerous germinal centers, and
      suffered from glomerulonephritis as a result of autoantibody production. These
      data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in
      the germinal centers and that its failure can lead to autoimmune diseases.

PMID- 15155947
TI  - Discovery and directed evolution of a glyphosate tolerance gene.
AB  - The herbicide glyphosate is effectively detoxified by N-acetylation. We screened
      a collection of microbial isolates and discovered enzymes exhibiting glyphosate N
      acetyltransferase (GAT) activity. Kinetic properties of the discovered enzymes
      were insufficient to confer glyphosate tolerance to transgenic organisms. Eleven
      iterations of DNA shuffling improved enzyme efficiency by nearly four orders of
      magnitude from 0.87 mM-1 min-1 to 8320 mM-1 min-1. From the fifth iteration and
      beyond, GAT enzymes conferred increasing glyphosate tolerance to Escherichia
      coli, Arabidopsis, tobacco, and maize. Glyphosate acetylation provides an
      alternative strategy for supporting glyphosate use on crops.

PMID- 15155948
TI  - Disulfide-dependent multimeric assembly of resistin family hormones.
AB  - Resistin, founding member of the resistin-like molecule (RELM) hormone family, is
      secreted selectively from adipocytes and induces liver-specific antagonism of
      insulin action, thus providing a potential molecular link between obesity and
      diabetes. Crystal structures of resistin and RELMbeta reveal an unusual
      multimeric structure. Each protomer comprises a carboxy-terminal disulfide-rich
      beta-sandwich "head" domain and an amino-terminal alpha-helical "tail" segment.
      The alpha-helical segments associate to form three-stranded coiled coils, and
      surface-exposed interchain disulfide linkages mediate the formation of tail-to
      tail hexamers. Analysis of serum samples shows that resistin circulates in two
      distinct assembly states, likely corresponding to hexamers and trimers. Infusion
      of a resistin mutant, lacking the intertrimer disulfide bonds, in pancreatic
      insulin clamp studies reveals substantially more potent effects on hepatic
      insulin sensitivity than those observed with wild-type resistin. This result
      suggests that processing of the intertrimer disulfide bonds may reflect an
      obligatory step toward activation.

PMID- 15155949
TI  - Genetic structure of the purebred domestic dog.
AB  - We used molecular markers to study genetic relationships in a diverse collection
      of 85 domestic dog breeds. Differences among breeds accounted for approximately
      30% of genetic variation. Microsatellite genotypes were used to correctly assign
      99% of individual dogs to breeds. Phylogenetic analysis separated several breeds
      with ancient origins from the remaining breeds with modern European origins. We
      identified four genetic clusters, which predominantly contained breeds with
      similar geographic origin, morphology, or role in human activities. These results
      provide a genetic classification of dog breeds and will aid studies of the
      genetics of phenotypic breed differences.

PMID- 15155950
TI  - Mutational analysis of the tyrosine phosphatome in colorectal cancers.
AB  - Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and
      kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A
      mutational analysis of the tyrosine phosphatase gene superfamily in human cancers
      identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13,
      PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung,
      breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or
      splice-site alterations predicted to result in truncated proteins lacking
      phosphatase activity. Five missense mutations in the most commonly altered PTP
      (PTPRT) were biochemically examined and found to reduce phosphatase activity.
      Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited
      cell growth. These observations suggest that the mutated tyrosine phosphatases
      are tumor suppressor genes, regulating cellular pathways that may be amenable to
      therapeutic intervention.

PMID- 15155951
TI  - The involvement of the orbitofrontal cortex in the experience of regret.
AB  - Facing the consequence of a decision we made can trigger emotions like
      satisfaction, relief, or regret, which reflect our assessment of what was gained
      as compared to what would have been gained by making a different decision. These
      emotions are mediated by a cognitive process known as counterfactual thinking. By
      manipulating a simple gambling task, we characterized a subject's choices in
      terms of their anticipated and actual emotional impact. Normal subjects reported
      emotional responses consistent with counterfactual thinking; they chose to
      minimize future regret and learned from their emotional experience. Patients with
      orbitofrontal cortical lesions, however, did not report regret or anticipate
      negative consequences of their choices. The orbitofrontal cortex has a
      fundamental role in mediating the experience of regret.

PMID- 15155952
TI  - Definition of a bacterial type IV secretion pathway for a DNA substrate.
AB  - Bacteria use conjugation systems, a subfamily of the type IV secretion systems,
      to transfer DNA to recipient cells. Despite 50 years of research, the
      architecture and mechanism of action of the channel mediating DNA transfer across
      the bacterial cell envelope remains obscure. By use of a sensitive, quantifiable
      assay termed transfer DNA immunoprecipitation (TrIP), we identify contacts
      between a DNA substrate (T-DNA) and 6 of 12 components of the VirB/D4 conjugation
      system of the phytopathogen Agrobacterium tumefaciens. Our results define the
      translocation pathway for a DNA substrate through a bacterial conjugation
      machine, specifying the contributions of each subunit of the secretory apparatus
      to substrate passage.

PMID- 15155954
TI  - Cerebral microbleeds: prevalence and associations with cardiovascular risk
      factors in the Framingham Study.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are areas of low signal
      intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI)
      corresponding to hemosiderin deposits in the perivascular space. Microangiopathy
      from atherosclerosis or amyloid angiopathy might lead to the formation of these
      lesions; therefore, there may be associations between CMBs and cardiovascular
      risk factors, APOE allele status, and brain morphology. We examined these
      relationships in the Framingham Study (FHS). METHODS: In 472 subjects from the
      FHS Offspring and Cohort, we related CMB status to age, sex, systolic blood
      pressure, total cholesterol and high-density lipoprotein cholesterol (HDL-C)
      levels, smoking, diabetes, total hemispheric brain volume, white matter
      hyperintensity volume (WMHV), and APOE allele status. RESULTS: Overall prevalence
      of CMBs was 4.7%, but CMBs were more prevalent with advanced age and male sex.
      Blood pressure, brain volume, and WMHV were related to CMBs in crude analysis but
      not after adjustment for age and sex. There were no significant relationships
      demonstrated between CMBs and APOE allele status, cholesterol, smoking, or
      diabetes. CONCLUSIONS: There is a low prevalence of CMBs in the community and a
      strong relationship with increasing age and male sex. We found no independent
      relationships with cardiovascular risk factors, APOE status, brain volumes, or
      WMH.

PMID- 15155955
TI  - Transcranial infrared laser therapy improves clinical rating scores after embolic
      strokes in rabbits.
AB  - BACKGROUND AND PURPOSE: Because photon energy delivered using a low-energy
      infrared laser may be useful to treat stroke, we determined whether transcranial
      laser therapy would improve behavioral deficits in a rabbit small clot embolic
      stroke model (RSCEM). METHODS: In this study, the behavioral and physiological
      effects of laser treatment were measured. The RSCEM was used to assess whether
      low-energy laser treatment (7.5 or 25 mW/cm2) altered clinical rating scores
      (behavior) when given to rabbits beginning 1 to 24 hours postembolization.
      Behavioral analysis was conducted from 24 hours to 21 days after embolization,
      allowing for the determination of the effective stroke dose (P50) or clot amount
      (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM,
      a treatment is considered beneficial if it significantly increases the P50
      compared with the control group. RESULTS: In the present study, the P50 value for
      controls were 0.97+/-0.19 mg to 1.10+/-0.17 mg; this was increased by 100% to
      195% (P50=2.02+/-0.46 to 2.98+/-0.65 mg) if laser treatment was initiated up to 6
      hours, but not 24 hours, postembolization (P50=1.23+/-0.15 mg). Laser treatment
      also produced a durable effect that was measurable 21 days after embolization.
      Laser treatment (25 mW/cm2) did not affect the physiological variables that were
      measured. CONCLUSIONS: This study shows that laser treatment improved behavioral
      performance if initiated within 6 hours of an embolic stroke and the effect of
      laser treatment is durable. Therefore, transcranial laser treatment may be useful
      to treat human stroke patients and should be further developed.

PMID- 15155956
TI  - Serial changes in platelet activation in patients after ischemic stroke: role of
      pharmacodynamic modulation.
AB  - BACKGROUND AND PURPOSE: Enhanced platelet activity has previously been reported
      in the acute phase after ischemic stroke. We tested the hypothesis that activated
      platelets (expressed by CD62p) are substantially increased in the acute stage
      after a stroke and decrease thereafter, and that antiplatelet therapies can
      suppress CD62p expression. METHODS: We serially examined platelet CD62p
      expression using flow cytometry after acute ischemic stroke in 87 consecutive
      patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33
      at-risk control subjects. RESULTS: CD62p expression was significantly higher in
      the acute phase after ischemic stroke than in normal and at-risk control subjects
      (both P<0.0001). CD62p expression decreased to a significantly lower level on day
      21, and to a substantially lower level on day 90. CD62p expression was not
      significantly suppressed by warfarin. However, CD62p expression was significantly
      suppressed by aspirin treatment (P=0.024) and more substantially suppressed by
      clopidogrel (P<0.0001) on day 90. Furthermore, only clopidogrel treatment
      (P=0.0016) was significantly independently associated with decreased CD62p
      expression on day 90. CONCLUSIONS: Platelet activation was significantly
      increased in acute ischemic stroke and substantially decreased thereafter. The
      lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel
      raises the prospect of the need for more effective antiplatelet agents or a
      synergistic combination therapy for stroke prevention in the future.

PMID- 15155960
TI  - Comparison of hypertension management after stroke and myocardial infarction:
      results from ECLAT1--a French nationwide study.
AB  - BACKGROUND AND PURPOSE: Hypertension control is a cornerstone of preventive
      treatment in patients at risk for cerebral attack. The aim of this study was to
      analyze hypertension management in secondary prevention of stroke as compared
      with patients in secondary prevention of myocardial infarction (MI). METHODS: The
      ECLAT1 study was a cross-sectional study conducted in all French regions in a
      random sample of 3009 practitioners. Patients with a documented history of
      atherothrombotic disease were included. Risk factors and the last measurement of
      blood pressure (BP) available in the medical record were noted. In the current
      study, patients with treated hypertension and a unique manifestation of
      atherothrombotic disease, ischemic stroke or MI, were analyzed. RESULTS: Among
      the 4346 patients included in the ECLAT1 study, 1416 patients with treated
      hypertension and stroke or MI were analyzed. Hypertension control was poorer in
      patients with stroke as compared with patients with MI (24.56% versus 34.16%
      P<0.01). Compared with patients with MI, systolic BP (140.61+/-14.14 versus
      144.21+/-14.99; P<0.0001), pulse pressure (59.91+/-11.94 versus 62.48+/-12.49;
      P<0.001), and, to a lesser extent, diastolic BP (80.69+/-8.39 versus 81.72+/
      8.85; P<0.05) were higher in stroke patients. Moreover, antihypertensive
      monotherapy was more frequently used in stroke than in MI patients (43.16% versus
      31.44% P<0.0001). CONCLUSIONS: With respect to the beneficial influence of tight
      BP control in secondary prevention of stroke, our results highlight the need for
      information provided to practitioners to recall the importance of hypertension
      control in this situation and to increase the use of combination therapy.

PMID- 15155959
TI  - Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a
      randomized, placebo-controlled safety study.
AB  - BACKGROUND AND PURPOSE: Direct thrombin inhibitors, including argatroban,
      represent an anticoagulant class distinct from heparins. We investigated the
      safety of 2 levels of argatroban anticoagulation in acute ischemic stroke.
      METHODS: This multicenter, randomized, double-blinded, placebo-controlled study
      included 171 patients with acute (< or =12 hours from onset) stroke and National
      Institutes of Health Stroke Scale (NIHSS) scores of 5 to 22. Patients received
      continuous intravenous argatroban (100 microg/kg bolus) at 3 microg/kg per minute
      (n=59) or 1 microg/kg per minute (n=58), respectively, adjusted to target
      activated partial thromboplastin times (aPTTs) 2.25x and 1.75x baseline or
      placebo (n=54) for 5 days. The primary outcome was symptomatic intracranial
      hemorrhage (ICH) at 30 days. RESULTS: Baseline characteristics including
      neurologic deficits (median NIHSS score 9) were comparable between groups.
      Argatroban at mean doses of 2.7 and 1.2 microg/kg per minute increased aPTTs
      significantly (P<0.001), with mean aPTTs at or near target values throughout
      infusion. Symptomatic ICH was not significantly different between groups (high
      dose argatroban, 5.1%; low-dose argatroban, 3.4%; placebo, 0%; P> or =0.18), with
      3 events during argatroban infusion and 2 events > or =7 days after stopping
      infusion. No significant between-group differences occurred in asymptomatic ICH
      (7 events), major systemic hemorrhage (no event), or 90-day mortality (13.4%
      overall). CONCLUSIONS: In this first North American randomized, double-blinded,
      placebo-controlled study of direct thrombin inhibition in acute ischemic stroke,
      argatroban at each dose evaluated significantly prolonged aPTTs without
      increasing ICH or major bleeding. These results suggest that argatroban provides
      safe anticoagulation in acute ischemic stroke, warranting future studies powered
      to evaluate its efficacy and more precisely estimate event rates.

PMID- 15155961
TI  - A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns
      and implications for clinical trials.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease
      causing stroke and dementia. The aim of this study was to explore the patterns of
      clinical progression in CADASIL, to check for prognostic variables, and to
      provide sample size estimates for future therapeutic trials. METHODS: Eighty
      CADASIL subjects (aged 45.7+/-9.9 years [mean+SD]) were followed prospectively
      during a mean period of 26.3+/-1.1 months. Standardized scales on disability
      (Rankin), activities of daily living (Barthel index), neurological outcome
      (National Institutes of Health Stroke Scale [NIHSS]), and cognition (structural
      interview for diagnosis of Alzheimer dementia and multi-infarct dementia [SIDAM]
      and Mattis dementia rating scale [MDRS]) were assessed at baseline and at follow
      up. RESULTS: All but 1 individual completed the protocol. At follow-up, the
      cohort had deteriorated with respect to all clinical scales: Rankin scores (0.3+/
      0.7 [mean change+/-SD]; P=0.001), Barthel index (-5.4+/-15.9; P<0.001), NIHSS
      scores (1.0+/-2.6; P=0.001), SIDAM scores (-2.1+/-6.4; P=0.004), and MDRS scores
      (-4.3+18.5; P=0.09). The spectrum ranged from marked worsening to some degree of
      improvement. Seventeen patients experienced a new stroke. Overall, there were 18
      strokes within 173 person-years, giving an average incidence rate of stroke of
      10.4 per 100 person-years (95% CI, 5.6 to 15.2). Age at baseline was found to be
      a predictor of clinical progression. Sample size estimates show that the number
      of individuals needed to include in an interventional trial (assumed duration 2
      years, assumed treatment effect 40%) is 602 when using stroke occurrence as an
      outcome measure. CONCLUSIONS: The clinical course of CADASIL includes periods of
      acute worsening, chronic progression, stabilization, and improvement. Sample size
      calculations emphasize the need for surrogate markers of disease progression for
      future interventional trials.

PMID- 15155963
TI  - Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage
      sensitive Ca2+ channels.
AB  - BACKGROUND AND PURPOSE: Because of their mixed estrogen-agonist and estrogen
      antagonist properties, selective estrogen receptor modulators (SERMs) are
      considered promising substitutes for hormone replacement therapy. Raloxifene and
      other SERMs confer estrogen-like cardiovascular protective effects but lack the
      carcinogenic activity of exogenous estrogen. However, little is known about the
      cerebrovascular action of raloxifene. Therefore, we studied the effects of
      raloxifene on the mechanisms regulating rat cerebral artery tone. METHODS: Ring
      segments of the isolated rat posterior communicating cerebral arteries were
      mounted in a microvessel myograph for measurement of isometric tension. Whole
      cell L-type voltage-sensitive Ca2+ currents were recorded using the perforated
      patch-clamp technique. Raloxifene (0.1 to 10 micromol/L) reduced the contractile
      responses to U46619, phenylephrine, and endothelin-1 in normal Krebs solution or
      to CaCl2 in Ca2+-free, high K+-containing solution. Raloxifene-induced relaxation
      was identical in endothelium-intact and endothelium-denuded rings. ICI 182780 had
      no effect on raloxifene-induced relaxation. Raloxifene reduced L-type Ca2+
      currents with a pD2 of 5.98+/-0.06, close to that (6.44+/-0.09) for raloxifene
      induced relaxation of 60 mmol/L K+-contracted rings. CONCLUSIONS: This study
      demonstrates that raloxifene acutely relaxes rat cerebral arteries largely via an
      endothelium-independent mechanism, involving inhibition of Ca2+ influx through L
      type Ca2+ channels.

PMID- 15155964
TI  - Comparison of perfusion computed tomography and computed tomography angiography
      source images with perfusion-weighted imaging and diffusion-weighted imaging in
      patients with acute stroke of less than 6 hours' duration.
AB  - BACKGROUND AND PURPOSE: We aimed to determine the diagnostic value of perfusion
      computed tomography (PCT) and CT angiography (CTA) including CTA source images
      (CTA-SI) in comparison with perfusion-weighted magnetic resonance imaging (MRI)
      (PWI) and diffusion-weighted MRI (DWI) in acute stroke <6 hours. METHODS:
      Noncontrast-enhanced CT, PCT, CTA, stroke MRI, including PWI and DWI, and MR
      angiography (MRA), were performed in patients with symptoms of acute stroke
      lasting <6 hours. We analyzed ischemic lesion volumes on patients' arrival as
      shown on NECT, PCT, CTA-SI, DWI, and PWI (Wilcoxon, Spearman, Bland-Altman) and
      compared them to the infarct extent as shown on day 5 NECT. RESULTS: Twenty-two
      stroke patients underwent CT and MRI scanning within 6 hours. PCT time to peak
      (PCT-TTP) volumes did not differ from PWI-TTP (P=0.686 for patients who did not
      undergo thrombolysis/P=0.328 for patients who underwent thrombolysis), nor did
      PCT cerebral blood volume (PCT-CBV) differ from PWI-CBV (P=0.893/P=0.169). CTA-SI
      volumes did not differ from DWI volumes (P=0.465/P=0.086). Lesion volumes
      measured in PCT maps significantly correlated with lesion volumes on PWI
      (P=0.0047, r=1.0/P=0.0019, r=0.897 for TTP; P=0.0054, r=0.983/P=0.0026, r=0.871
      for CBV). Also, PCT-CBV lesion volumes significantly correlated with follow-up CT
      lesion volumes (P=0.0047, r=1.0/P=0.0046, r=0.819). CONCLUSIONS: In hyperacute
      stroke, the combination of PCT and CTA can render important diagnostic
      information regarding the infarct extent and the perfusion deficit. Lesions on
      PCT-TTP and PCT-CBV do not differ from lesions on PWI-TTP and PWI-CBV; lesions on
      CTA source images do not differ from lesions on DWI. The combination of
      noncontrast-enhanced CT (NECT), perfusion CT (PCT), and CT angiography (CTA) can
      render additional information within <15 minutes and may help in therapeutic
      decision-making if PWI and DWI are not available or cannot be performed on
      specific patients.

PMID- 15155965
TI  - Usefulness of ambulatory 7-day ECG monitoring for the detection of atrial
      fibrillation and flutter after acute stroke and transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Although atrial fibrillation is the most frequent cause
      of cardioembolic stroke, this arrhythmia remains underdiagnosed, as it is often
      asymptomatic or intermittent and, thus, may not be detected on standard 12-lead
      ECG or even 24-hour ECG recording (Holter). In this study, we hypothesized that 7
      day ambulatory ECG monitoring using an event-loop recording (ELR) device would
      detect otherwise occult episodes atrial fibrillation and flutter (AF) after acute
      stroke or transient ischemic attack (TIA). METHODS: One hundred forty-nine
      consecutive patients admitted to our neurology department with an acute stroke or
      TIA were systematically screened for emboligenic arrhythmias using standard ECG.
      In the absence of AF on standard ECG, patients underwent 24-hour ECG recording
      (Holter), which was followed by a 7-day ambulatory ECG monitoring (ELR) in
      patients with a normal Holter. Patients with previously documented persistent AF,
      with primary hemorrhagic stroke, or with acute large vessel dissection were not
      included in the study. RESULTS: AF was detected in 22 patients. Standard ECG
      identified AF in 2.7% of the cases at admission (4/149 patients) and in 4.1% of
      remaining patients within 5 days (6/145). Holter disclosed AF in 5% of patients
      with a normal standard ECG (7/139 patients), whereas ELR detected AF in 5.7% of
      patients with a normal standard ECG and normal Holter (5/88 patients).
      CONCLUSIONS: Following acute stroke or TIA, ELR identified patients with AF,
      which remained undetected with standard ECG and with Holter. ELR should,
      therefore, be considered in every patient in whom a cardioembolic mechanism is
      suspected.

PMID- 15155966
TI  - Hyperexcitability-associated rapid plasticity after a focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: This article addresses how neuroplastic changes are
      initiated after an ischemic stroke. METHODS: A focal cerebral ischemia was
      photochemically induced on the primary somatosensory cortex of rats, and in vivo
      electrophysiological recordings were performed on the peri-infarct cortex before
      and from 1 to 6 hours after the infarction. RESULTS: Paired-pulse analysis of
      evoked field potentials to peripheral electrical stimuli showed statistically
      significant neuronal hyperexcitability that was associated with rapid expansion
      of receptive fields (146.1% at 1 hour and 553.6% at 6 hours) as early as 1 hour
      after the infarction (P<0.05). Current source density analysis revealed increased
      current sinks in cortical layer II/III. CONCLUSIONS: Our electrophysiological
      results showed, for the first time to our knowledge, rapid plastic changes in the
      peri-infarct cortex during the hyperacute stage of an ischemic stroke.
      Manipulation of this rapid plasticity may affect subsequent plastic changes.

PMID- 15155967
TI  - Monocyte count, but not C-reactive protein or interleukin-6, is an independent
      risk marker for subclinical carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Systemic inflammatory markers have been shown to predict
      future cardiovascular events, but whether they are associated with early
      atherosclerosis is uncertain. We investigated the relationship of inflammatory
      markers interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP),
      fibrinogen, monocyte count, and white cell count (WCC) with subclinical carotid
      atherosclerosis in a healthy community population. METHODS: B-mode carotid
      ultrasound was performed on 1111 randomly selected male and female subjects aged
      27 to 77 years. Serum IL-6, hs-CRP, plasma fibrinogen, monocyte count, and WCC
      were measured on all subjects, along with conventional cardiovascular risk
      factors. RESULTS: Multivariate analysis showed that IL-6 (P<0.0001), fibrinogen
      (P=0.007), and monocyte count (P=0.001) were associated with carotid plaque
      formation in the whole population. Monocyte count remained associated
      independently with carotid plaque formation when adjusted further for
      conventional risk factors (odds ratio per SD increase in monocyte count 1.4; 95%
      CI, 1.13 to 1.73; P=0.002). IL-6 (P<0.0001), fibrinogen (P<0.0001), and monocyte
      count (P=0.04) were also associated with carotid intima-medial thickness (IMT) in
      the whole population. However, when adjusted further for conventional risk
      factors, none remained independently predictive of carotid IMT. Further analysis
      showed an age-monocyte interaction (P=0.03), with monocyte count being an
      independent predictor of carotid IMT in the older age group only (>53 years;
      P=0.003). CONCLUSIONS: In a healthy community population, monocyte count is a
      better independent predictor of common carotid IMT and plaque formation than IL
      6, hs-CRP, fibrinogen, and WCC. Monocyte count may represent an inexpensive, easy
      to-measure risk marker for subclinical carotid atherosclerosis.

PMID- 15155968
TI  - Fish consumption and incidence of stroke: a meta-analysis of cohort studies.
AB  - BACKGROUND AND PURPOSE: Results from observational studies on fish consumption
      and risk of stroke are inconsistent. We quantitatively assessed the relationship
      between fish intake and incidence of stroke using a meta-analysis of cohort
      studies. METHODS: We searched the Medline and Embase databases (1966 through
      October 2003) and identified 9 independent cohorts (from 8 studies) that provided
      a relative risk (RR) and corresponding 95% CI for total or any type of stroke in
      relation to fish consumption. Pooled RR and 95% CI of stroke were estimated by
      variance-based meta-analysis. RESULTS: Compared with those who never consumed
      fish or ate fish less than once per month, the pooled RRs for total stroke were
      0.91 (95% CI, 0.79 to 1.06) for individuals with fish intake 1 to 3 times per
      month, 0.87 (95% CI, 0.77 to 0.98) for once per week, 0.82 (95% CI, 0.72 to 0.94)
      for 2 to 4 times per week, and 0.69 (95% CI, 0.54 to 0.88) for > or =5 times per
      week (P for trend=0.06). In stratified analyses of 3 large cohort studies with
      data on stroke subtypes, the pooled RRs across 5 categories of fish intake were
      1.0, 0.69 (95% CI, 0.48 to 0.99), 0.68 (95% CI, 0.52 to 0.88), 0.66 (95% CI, 0.51
      to 0.87), and 0.65 (95% CI, 0.46 to 0.93) for ischemic stroke (P for trend=0.24);
      and 1.0, 1.47 (95% CI, 0.81 to 2.69), 1.21 (95% CI, 0.78 to 1.85), 0.89 (95% CI,
      0.56 to 1.40), and 0.80 (95% CI, 0.44 to 1.47) for hemorrhagic stroke (P for
      trend=0.31). CONCLUSIONS: These results suggest that intake of fish is inversely
      related to risk of stroke, particularly ischemic stroke. Fish consumption as
      seldom as 1 to 3 times per month may protect against the incidence of ischemic
      stroke.

PMID- 15155969
TI  - Effect of untreated hypertension on hemorrhagic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and the
      leading cause of disability in the United States. Intracerebral hemorrhage and
      subarachnoid hemorrhage represent approximately 20% of all stroke cases and have
      a mortality rate of 40% to 50%. Hypertension is an important risk factor for
      these subtypes of stroke. We sought to determine whether untreated hypertension
      carries a different risk from treated hypertension for hemorrhagic stroke.
      METHODS: Cases of hemorrhagic stroke in the greater Cincinnati region were
      identified by screening all area hospital emergency rooms, radiology reports, and
      International Classification of Diseases 9 codes. Medical records were reviewed
      for risk factors and medication use. Cases of hemorrhagic stroke were approached
      for enrollment into the genetic sampling and interview arm. If subjects agreed,
      the case was matched by age, race, and gender to population-based controls.
      RESULTS: Between May 1997 and December 2002, we recruited 549 cases of
      hemorrhagic stroke, of which 322 were intracerebral hemorrhage and 227 were
      subarachnoid hemorrhage. Untreated hypertension was found to be a significant
      risk factor for hemorrhagic stroke (odds ratio [OR]=3.5 [2.3 to 5.2]; P<0.0001)
      as was treated hypertension (OR=1.4 [1.0 to 1.9]; P=0.03). Insurance status of
      "self-pay" or Medicaid was a significant risk factor for untreated hypertension
      (OR=2.7 [1.6 to 4.4]). We estimate that 17% to 28% of hemorrhagic strokes among
      hypertensive patients would have been prevented if they had been on hypertension
      treatment. CONCLUSIONS: Untreated hypertension is highly prevalent and an
      important risk factor for hemorrhagic stroke. We estimate that among hypertensive
      subjects, approximately one fourth of hemorrhagic strokes would be prevented if
      all hypertensive subjects received treatment.

PMID- 15155970
TI  - Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke:
      an imaging-based study.
AB  - BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils
      in acute cerebral ischemia. We have studied the patterns and temporal profile of
      cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have
      attempted to correlate this with neurological status and outcome. METHODS:
      Patients with cortical middle cerebral artery (MCA) IS were recruited within 24
      hours of clinical onset. Neutrophil recruitment was studied using indium-111
      (111In) troponolate-labeled neutrophils, planar imaging, and single-photon
      emission computed tomography (SPECT). Volume of brain infarction was calculated
      from concurrent computed tomography (CT). Hematoxylin and eosin sections were
      obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and
      National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients
      were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere,
      as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in
      9 patients; this response was heterogenous between patients and on repeated
      measurement attenuated over time. Histologically, recruitment was confirmed
      within intravascular, intramural, and intraparenchymal compartments.
      Interindividual heterogeneity in neutrophil response did not correlate with
      infarct volume or outcome. In an exploratory analysis, neutrophil accumulation
      appeared to correlate significantly with infarct expansion (Spearman rho=0.66;
      P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within
      24 hours of symptom onset. This recruitment attenuates over time and is confirmed
      histologically. While neutrophil accumulation may be associated with either the
      magnitude or the rate of infarct growth, these results require confirmation in
      future studies.

PMID- 15155971
TI  - Relationship between C-reactive protein and progression of early carotid
      atherosclerosis in hypertensive subjects.
AB  - BACKGROUND AND PURPOSE: Hypertensive outpatients were investigated for C-reactive
      protein (CRP) and carotid atherosclerosis because the influence of CRP on the
      progression of subclinical atherosclerosis in hypertensives remains unclear.
      METHODS: A total of 124 outpatients (aged 40 to 79 years) in treatment for
      hypertension were enrolled. They underwent repeated ultrasonographic evaluation
      of the carotid arteries for 35+/-12 months. Focal intima-media thickening of > or
      =1.1 mm was defined as plaque, and the plaque number, plaque score, and the sum
      of all plaque thickness were calculated. RESULTS: Multivariate linear regression
      analysis revealed that CRP, pulse pressure, and systolic blood pressure were
      related to the annual change of plaque number (beta=0.34, 0.27, and 0.30; all
      P<0.01) and plaque score (beta=0.38, 0.27, and 0.23; P<0.001, P<0.01, and P<0.05,
      respectively) independently of other risk factors. In 64 patients taking
      antihypertensive medications with a blood pressure of <140/90 mm Hg, CRP and the
      pulse pressure were related to the annual change of plaque number (r=0.40 and
      0.26; P<0.01 and P<0.05, respectively) and plaque score (r=0.44 and 0.31; P<0.001
      and P<0.05, respectively). CONCLUSIONS: In hypertensive patients being managed by
      drug therapy or lifestyle modification, CRP is an equivalent or superior
      independent predictor of the progression of carotid atherosclerosis than the
      pulse pressure or systolic blood pressure.

PMID- 15155973
TI  - Temperature-regulated model of focal ischemia in the mouse: a study with
      histopathological and behavioral outcomes.
AB  - BACKGROUND AND PURPOSE: The importance of mouse stroke models has increased with
      the development of genetically manipulated animals. We hypothesized that
      immediate postischemia hypothermia may attenuate ischemic brain injury in the
      mouse. METHODS: Intraabdominal radio frequency probes were implanted in animals
      and core temperature monitored. Groups included: MCAO-45-REG (45 minutes middle
      cerebral artery occlusion [MCAO]) temperature-controlled in the postischemic
      period >34 degrees C for 24 hours; MCAO-45 (45 minutes MCAO) were allowed to self
      regulate core temperature during recovery; MCAO-30-REG (30 minutes MCAO), with
      the same temperature protocol as MCAO-45-REG; MCAO-30 (30 minutes MCAO), with
      temperature protocol the same as MCAO-45. Behavior and histological score was
      assessed at 7 days. The qualitative histological score assessed for injury in 18
      specified regions. RESULTS: MCAO-45-REG core temperature (mean 34.94 degrees C+/
      0.8 degrees C) was significantly different than the self-regulating (MCAO-45,
      mean 33.1 degrees C+/-2.3 degrees C) for the first 4 hours after anesthesia
      (P<0.01). There was a trend toward similar differences in temperatures for MCAO
      30-REG and MCAO-30 (P=0.08). At 7 days, a greater improvement in behavior score
      was observed for MCAO-45 and MCAO-30 compared with MCAO-45-REG and MCAO-30-REG
      (P<0.001). The histological score confirmed reduced injury in unregulated
      temperature groups (MCAO-45-REG mean 38+/-10 and MCAO-45 30+/-5.1, P<0.05; MCAO
      30-REG 41+/-10 and MCAO-30 30+/-9, P<0.05). CONCLUSIONS: Hypothermia is an
      important confounder of stroke injury in the intraluminal filament mouse model.
      Future mouse stroke studies must use strict temperature regulation.

PMID- 15155974
TI  - Ischemic stroke subtypes: a population-based study of incidence rates among
      blacks and whites.
AB  - BACKGROUND AND PURPOSE: Blacks have an excess burden of stroke compared with
      whites; however, data comparing ischemic stroke subtypes among the 2 groups are
      limited and typically involve relative frequencies. The objective of this study
      is to compare the incidence rates of ischemic stroke subtypes between blacks and
      whites within a large, representative, biracial population. METHODS: The Greater
      Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates
      and trends of all strokes within a well-defined, large, biracial population.
      Hospitalized cases were ascertained by International Classification of Disease
      (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by
      prospective screening of emergency department admission logs, review of coroners'
      cases, and monitoring all public health and hospital-based primary care clinics.
      A sampling scheme was used to ascertain events from nursing homes and all other
      primary care physician offices. All potential cases underwent detailed chart
      abstraction and confirmed by physician review. Based on all available clinical,
      laboratory, and radiographic information, ischemic stroke cases were subtyped
      into the following categories: cardioembolic, large-vessel, small-vessel, other,
      and stroke of undetermined cause. Race-specific incidence rates were calculated
      and compared after adjusting for age and gender, and standardizing to the 1990 US
      population. RESULTS: Between July 1, 1993, and June 30, 1994, 1956 first-ever
      ischemic strokes occurred among blacks and whites in the study population. Small
      vessel strokes and strokes of undetermined cause were nearly twice as common
      among blacks. Large-vessel strokes were 40% more common among blacks than whites,
      and there was a trend toward cardioembolic strokes being more common among
      blacks. CONCLUSIONS: The excess burden of ischemic strokes among blacks compared
      with whites is not uniformly spread across the different subtypes. Large-vessel
      strokes are more common and cardioembolic stroke are as common among blacks,
      traditionally thought to be more common among whites.

PMID- 15155975
TI  - Ultrasound microbubble destruction imaging in acute middle cerebral artery
      stroke.
AB  - BACKGROUND AND PURPOSE: Cerebral perfusion imaging in acute stroke assists in
      determining the subtype and the severity of ischemia. Recent studies in perfusion
      models and in healthy volunteers have shown that ultrasound perfusion imaging
      based on microbubble destruction can be used to assess tissue perfusion. We
      applied ultrasound microbubble destruction imaging (MDI) to identify perfusion
      deficits in patients with acute middle cerebral artery (MCA) territory stroke.
      METHODS: Fifteen acute MCA stroke patients with sufficient transtemporal bone
      windows were investigated with ultrasound MDI and perfusion-weighted MRI (PWI).
      MDI was performed using power pulse-inversion contrast harmonic imaging. Thirty
      seconds after a bolus injection of the echo contrast agent SonoVue, microbubbles
      were destroyed using a series of high-energy pulses. Local perfusion status was
      analyzed in selected regions of interest by destruction curves and acoustic
      intensity differences (DeltaI) before and after microbubble destruction. Local
      perfusion status was then compared with perfusion compromise as identified on
      PWI. RESULTS: The mean differences of acoustic intensity from the ischemic MCA
      territory were significantly diminished compared with the normal hemisphere
      (DeltaI=2.52+/-1.75 versus DeltaI=13.79+/-7.31; P<0.001), resulting in lower
      slopes of microbubble destruction. PWI confirmed perfusion changes in the
      selected anatomical regions on time-to-peak maps in all 15 patients. CONCLUSIONS:
      MDI is a qualitative method that can rapidly detect perfusion changes in acute
      stroke. When combined with other ultrasound techniques and PWI, it may well be
      valuable in the care of stroke unit patients, eg, as a screening method and for
      follow-up assessments of perfusion deficits.

PMID- 15155977
TI  - Comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for
      uncomplicated Plasmodium falciparum malaria and impact on gametocyte carriage
      rates in the East Nusatenggara province of Indonesia.
AB  - The efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was evaluated
      in 89 subjects greater than one year of age with uncomplicated P. falciparum
      malaria in the East Nusatenggara Province of Indonesia. Fever clearance time was
      longer in the SP group than in the CQ group. However, parasite clearance time was
      extended in subjects who received CQ compared with those who received SP. Major
      adverse events were not observed in either group, and no hospitalizations were
      required during the study. Treatment failure rates at day 28 were 69% for CQ and
      8.5% for SP. In both treatment groups, gametocytemia developed during the follow
      up period, but was more pronounced in the SP group, peaking at 94% on day 7.
      Regardless of treatment group, children < 10 years of age had significantly
      higher treatment failure rates than subjects >/=10 years of age (relative risk =
      2.49), suggesting that acquired immunity influenced treatment outcomes in the
      presence of parasite drug resistance. Although a highly effective alternative to
      CQ for clearing infection, SP treatment also presented some potential drawbacks
      (e.g., increased and persistent gametocytemia). Replacement of CQ with SP as a
      first-line therapy, either alone or in combination with CQ, in those areas of
      Indonesia with high levels of CQ resistance should significantly improve
      treatment outcomes, particularly in vulnerable populations lacking clinical
      immunity. More efficacious and rapidly acting asexual stage treatments are
      generally associated with increased gametocyte clearance and combination therapy
      in areas where drug resistance is high or emerging may provide an additional
      means for reducing transmission.

PMID- 15155976
TI  - Polymorphism of the Plasmodium falciparum multidrug resistance and chloroquine
      resistance transporter genes and in vitro susceptibility to aminoquinolines in
      isolates from the Peruvian Amazon.
AB  - In vitro drug sensitivity to chloroquine (CQ), mefloquine (MQ) and quinine was
      investigated in 60 culture-adapted Plasmodium falciparum isolates from malaria
      patients in Padrecocha, a village in the Amazonian Department of Loreto, Peru.
      All isolates showed resistance to CQ, decreased susceptibility to quinine, and
      sensitivity to MQ. These isolates were examined for mutations in the P.
      falciparum multidrug resistance 1 (pfmdr1) and chloroquine resistance transporter
      (pfcrt) genes previously linked to CQ resistance. The mutations N86Y and D1246Y,
      two of the five mutations commonly observed in the pfmdr1 gene of CQ-resistant
      clones, were not found. The pfcrt mutation K76T, associated with CQ resistance,
      was identified in all the isolates tested. Sequence analysis of codons 72-76 in
      the pfcrt gene showed the haplotypes SVMNT and CVMNT.

PMID- 15155978
TI  - Molecular epidemiology of malaria in cameroon. XX. Experimental studies on
      various factors of in vitro drug sensitivity assays using fresh isolates of
      Plasmodium falciparum.
AB  - The influence of several factors on parasite growth and 50% inhibitory
      concentration (IC(50)) for chloroquine was assessed. Most isolates stored at 4
      degrees C up to 72 hours grew when they were subsequently cultivated. However,
      parasite viability sharply decreased from 24 hours, and the mean chloroquine
      IC(50) decreased significantly (P < 0.05). There was no evidence for selection of
      pre-culture populations due to storage alone. The time point when (3)H
      hypoxanthine was added (0 versus 18 hours) had no effect on the IC(50) during the
      42-hour incubation, but was associated with a lower IC(50) when (3)H-hypoxanthine
      was added after the initial 42-hour incubation during the 72-hour incubation. An
      increase in 3H-hypoxanthine incorporation and chloroquine IC(50) was observed as
      the hematocrit was increased from 1.0% to 2.5%. For the same isolates,
      chloroquine IC(50) values were generally similar when the initial parasitemia was
      between 0.1% and 0.5% but increased at higher (>0.75%) parasitemias. Based on
      these results, we recommend immediate cultivation after blood collection, a 42
      hour incubation period with the addition of (3)H-hypoxanthine at the beginning of
      incubation, a 1.5% hematocrit, and an initial parasitemia 0.1-0.5%. Further
      studies on serum substitutes, gas mixture, and comparison of isotopic and non
      isotopic assays are needed to establish a standardized in vitro assay protocol.

PMID- 15155979
TI  - Evaluation of a malaria rapid diagnostic test for assessing the burden of malaria
      during pregnancy.
AB  - Plasmodium falciparum infection during pregnancy may cause placental malaria and
      subsequently low birth weight, primarily through the placental sequestration of
      infected red blood cells. Measuring the burden of malaria during pregnancy
      usually involves determining the prevalence of placental malaria infection
      through microscopic examination of placental blood films, a difficult and error
      prone process. A number of rapid diagnostic tests (RDTs) for malaria have been
      developed, most of them immunochromatographic dipstick assays. However, none have
      been tested for the direct determination of malaria antigen in placental blood.
      We undertook an evaluation of the Malaria Rapid Test (MAKROmed in determining
      placental malaria infection. The prevalence of placental parasitemia was 22.6% by
      microscopy, 51.0% by a polymerase chain reaction (PCR), and 43.1% by RDT. When
      the PCR was used as the gold standard, RDTs had a sensitivity of 89% and a
      specificity of 76%. The MAKROmed RDT was highly sensitive in the detection of
      placental malaria, but had lower than expected specificity.

PMID- 15155980
TI  - A global index representing the stability of malaria transmission.
AB  - To relate stability of malaria transmission to biologic characteristics of vector
      mosquitoes throughout the world, we derived an index representing the
      contribution of regionally dominant vector mosquitoes to the force of
      transmission. This construct incorporated published estimates describing the
      proportion of blood meals taken from human hosts, daily survival of the vector,
      and duration of the transmission season and of extrinsic incubation. The result
      of the calculation was displayed globally on a 0.5 degrees grid. We found that
      these biologic characteristics of diverse vector mosquitoes interact with climate
      to explain much of the regional variation in the intensity of transmission. Due
      to the superior capacity of many tropical mosquitoes as vectors of malaria,
      particularly those in sub-Saharan Africa, antimalaria interventions conducted in
      the tropics face greater challenges than were faced by formerly endemic nations
      in more temperate climes.

PMID- 15155981
TI  - Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a
      adjuvant system, in infant rhesus monkeys.
AB  - Malaria vaccine RTS,S combined with thrombospondin-related anonymous protein
      (TRAP) and formulated with AS02A (RTS,S+TRAP/AS02A) is safe and immunogenic in
      adult humans and rhesus monkeys (Macaca mulatta). Here, RTS,S+TRAP/AS02A was
      administered on a 0-, 1-, and 3-month schedule to three cohorts of infant
      monkeys, along with adult comparators. Cohort 1 evaluated 1/5, 1/2, and full
      adult doses, with the first dose administration at one month of age; cohort 2
      monkeys received full adult doses, with the first dose administration at one
      versus three months of age; and, cohort 3 compared infants gestated in mothers
      with or without previous RTS,S/AS02A immunization. Immunization site
      reactogenicity was mild. Some infants, including the phosphate-buffered saline
      only recipient, developed transient iron-deficiency anemia, which is considered a
      result of repeated phlebotomies. All RTS,S+TRAP/AS02A regimens induced vigorous
      antibody responses that persisted through 12 weeks after the last vaccine dose.
      Modest lymphoproliferative and ELISPOT (interferon-gamma and interleukin-5)
      responses, particularly to TRAP, approximated adult comparators. RTS,S+TRAP/AS02A
      was safe and well tolerated. Vigorous antibody production and modest, selective
      cell-mediated immune responses suggest that RTS,S+TRAP/AS02A may be immunogenic
      in human infants.

PMID- 15155982
TI  - Seasonal variation in the risk and causes of maternal death in the Gambia:
      malaria appears to be an important factor.
AB  - An increase in maternal mortality risk during peak malaria transmission in
      endemic countries is thought to implicate malaria in maternal deaths. The purpose
      of this study was to evaluate changes in risk and causes of maternal death in
      relation to the malaria season at the main referral hospital in The Gambia.
      During the malaria season, there was a 168% increase in the maternal mortality
      ratio (MMR), a three-fold increase in the proportion of deaths due to anemia, and
      an eight-fold increase in the anemia MMR. Apart from a 5.4-fold increase in
      eclampsia, there was no significant change in the contribution of other causes of
      death. It is estimated that malaria may account for up to 93 maternal deaths per
      100,000 live births.

PMID- 15155983
TI  - Predicting triatoma dimidiata abundance and infection rate: a risk map for
      natural transmission of chagas disease in the yucatan peninsula of Mexico.
AB  - Chagas disease, a major public health problem in Latin America, is caused by the
      protozoan parasite Trypanosoma cruzi and transmitted by hematophageous insects
      from the Triatominae subfamily. Control of this disease is based on domestic
      vector control with insecticides and improvements in housing. As with other
      vector-borne diseases, the identification of areas of high risk of disease
      transmission is a major prerequisite for the planning and implementation of cost
      effective control programs. In this study, we explored the relationship between
      Triatoma dimidiata geographic distribution and bioclimatic factors in the Yucatan
      peninsula in Mexico, using geographic information systems, and developed
      predictive models of T. dimidiata domestic abundance and of its infection rates
      by T. cruzi. These predictions were then used to build the first natural
      transmission risk map for Chagas disease in the Yucatan peninsula, a tool that
      should prove very valuable for the implementation of effective vector control
      programs in the region.

PMID- 15155984
TI  - Buruli ulcer disease in Cameroon rediscovered.
AB  - To assess the magnitude of the Buruli ulcer (BU) problem in Cameroon, we
      conducted a cross-sectional survey in the Nyong River basin and identified on
      clinical grounds a total of 436 cases of active or inactive BU (202 and 234,
      respectively). Swab specimens were taken from 162 active cases with ulcerative
      lesions and in 135 of these (83.3%) the clinical diagnosis was confirmed by the
      IS2404 polymerase chain reaction. Most lesions (93%) were located on the
      extremities, with lower limbs being twice as commonly involved as upper limbs.
      The age of patients with active BU ranged from 2 to 90 years with a median age of
      14.5 years. Vaccination with bacilli Calmette-Guerin appeared to protect children
      against more severe forms of BU with multiple lesions. We conclude that in
      Cameroon BU is endemic, at least in the study area, and that a comprehensive
      control program for BU in Cameroon is urgently needed.

PMID- 15155985
TI  - Suspected small-scale interpersonal transmission of Mycobacterium tuberculosis in
      wards of an urban hospital in Delhi, India.
AB  - Genotypes of Mycobacterium tuberculosis causing disease were investigated in
      pulmonary tuberculosis patients admitted to two adjacent wards of a tuberculosis
      hospital in Delhi, India. Genetic markers, the insertion sequence IS6110, a
      direct repeat sequence, and a polymorphic GC-rich sequence supported the
      circumstantial epidemiologic link between eight strains of M. tuberculosis,
      suggesting their possible involvement in small-scale, interpersonal transmission
      of both drug-sensitive and drug-resistant tuberculosis. This is the first report
      of a suspected acquisition of M. tuberculosis among hospitalized patients in
      India. The use of multiple molecular typing markers and techniques unequivocally
      identified the exact clonality of strains isolated from the hospital. The result
      of this study emphasizes the need for more comprehensive investigation of high
      risk situations for tuberculosis transmission and long-term follow-up analysis
      for identifying such instances of unsuspected transmission.

PMID- 15155986
TI  - Tuberculous peritonitis in different dialysis patients in Southern Taiwan.
AB  - Eleven cases of tuberculous peritonitis (TBP) in hemodialysis (HD) and continuous
      ambulatory peritoneal dialysis (CAPD) patients at the Kaohsiung Veterans General
      Hospital in Kaohsiung, Taiwan between 1991 and 2000 were studied retrospectively
      (six cases in the HD group and five cases in the CAPD group) The diagnosis of TBP
      was established by either positive ascite tuberculosis (TB) culture or biopsy
      proven chronic granulomatous inflammation. Fever and abdominal pain were the most
      common symptoms, while leukocytosis and unexplained hypercalcemia were the most
      common laboratory findings. Ascite analysis showed a lymphocyte predominance in
      all HD patients, but in only 40% of the CAPD patients. The mean duration of a
      diagnosis by ascite TB cultures was six weeks, while a diagnosis confirmed by
      laparascopic biopsy took one week. All four fatal cases were diagnosed by TB
      cultures. Laparoscopic biopsy provided a rapid diagnosis and resulted in low
      morbidity and mortality in our patients. Based on our review of all possible
      abstracts found in a Medline search from 1966 to 2002 using the keywords
      tuberculosis, peritonitis, uremia, and dialysis, this may be the first study of
      TBP in different dialysis patients.

PMID- 15155987
TI  - Etiology of diarrhea in children less than five years of age in Ifakara,
      Tanzania.
AB  - A total of 451 stool specimens were collected from children less than five years
      of age with acute diarrhea from Ifakara, Tanzania and processed to detect
      bacterial enteropathogens, parasites, and rotaviruses. These specimens were
      divided into 348 from the dry season and 103 from the rainy season. Overall,
      diarrheogenic Escherichia coli (35.7%) were the predominant enteropathogens, with
      enterotoxigenic E. coli, enteroaggregative E. coli, and enteropathogenic E. coli
      being the most prevalent. Moreover, enteroaggregative E. coli (63% versus 35.5%;
      P < 0.05), Shigella spp. (24% versus 12%; P < 0.05), and rotavirus (23% versus
      4%; P < 0.05) were more prevalent in the dry season than in the rainy season and
      enterotoxigenic E. coli (51.6% versus 20%; P < 0.05) and Giardia lamblia (14%
      versus 1%; P < 0.05) were more prevalent in the rainy season.

PMID- 15155988
TI  - Q fever in children in Greece.
AB  - The aim of this study was to investigate the incidence, epidemiology, and
      clinical manifestations of Q fever among hospitalized children in Greece. During
      a two-year period, 1,200 children with various clinical manifestations were
      prospectively tested for Coxiella burnetii infection by indirect
      immunofluorescence. Acute Q fever was diagnosed in eight (0.67%) patients. No
      chronic case of infection was detected. Multivariate analysis showed that
      children 11-14 years old and children reporting consumption of cheese from rural
      areas were at increased risk for this illness. Clinical manifestations of acute Q
      fever were pneumonia (two patients), meningitis (two), prolonged fever (two),
      hepatitis (one), and hemolytic-uremic syndrome (one). Q fever accounted for 2.9%
      of the cases with prolonged fever, 1.2% of the cases of meningitis, and 0.5% of
      the cases of pneumonia. Fever and headache were the most common symptoms at
      presentation. Our study indicates that Q fever is a rare cause of hospitalization
      during childhood.

PMID- 15155989
TI  - Detection of Leishmania infantum kinetoplast DNA in peripheral blood from
      asymptomatic individuals at risk for parenterally transmitted infections:
      relationship between polymerase chain reaction results and other Leishmania
      infection markers.
AB  - Individuals with frequent exposures to agents spread through the parenteral route
      show a high prevalence of Leishmania seropositivity in Spain. However, the
      frequency of positive polymerase chain reaction (PCR) results for Leishmania in
      blood in this setting remains unknown. In this study, L. infantum kinetoplast DNA
      (kDNA) was found in blood from 23 (24%) of 95 asymptomatic individuals with a
      serum Leishmania antibody titer > or = 1:20 and in none of 44 seronegative
      individuals. The greater the antibody titer, the greater the proportion of PCR
      positive samples, but 16 (20%) of 81 individuals with antibody titers < or = 1:40
      tested positive by PCR. Nine (37%) PCR-positive and 22 (19%) (P = 0.03) PCR
      negative individuals showed a positive leishmanin skin test result. This results
      show that a remarkable proportion of asymptomatic Leishmania-seropositive
      individuals at risk for parenterally transmitted infections carry Leishmania kDNA
      in blood. This is more common in subjects with a high serum Leishmania antibody
      level and a positive leishmanin skin test result.

PMID- 15155990
TI  - Antigen-specific antibody isotype patterns to schistosoma japonicum recombinant
      and native antigens in a defined population in Leyte, the Philippines.
AB  - We describe antibody isotype patterns resulting from Schistosoma japonicum
      infection among 155 individuals 5-76 years old from a community in Leyte, The
      Philippines. Their exposure, infection, and reinfection status had been observed
      in a previously described water contact study used to categorically classify them
      as putative resistant or susceptible individuals. Antigens tested for specific
      antibody isotype responses were soluble worm antigen preparation (SWAP) and
      soluble egg antigen (SEA) and a panel of recombinant molecules. The study was
      aimed primarily at evaluating antigen-specific antibody responses and their
      potential in inducing protection among putative resistant individuals. Specific
      antibody responses suggestive of an involvement in protection were an IgE
      response to SWAP among females less than 20 years of age (5-19) and IgA responses
      to SWAP in the younger (5-19 years) age groups. Compatible with other studies on
      human schistosomes, IgM reactivities to SWAP and SEA in the 5-19-year-old age
      group predicted susceptibility as did IgG4 responses to recombinant paramyosin.

PMID- 15155991
TI  - A longitudinal study of impact of repeated mass ivermectin treatment on clinical
      manifestations of onchocerciasis in Imo State, Nigeria.
AB  - We conducted a cohort study on impact of effects of eight years of annual
      ivermectin mass treatment administered in eight villages in Imo State, Nigeria.
      Physical and visual acuity examinations carried out in 462 persons in 1995, prior
      to the launching of mass drug administration with ivermectin, were compared with
      re-examinations of 411 (89%) of these same individuals in 2002. We found that
      gross visual impairment decreased from 16% to 1%, nodule prevalence decreased
      from 59% to 18%, and papular dermatitis was reduced from 15% to 2%. No change was
      seen in leopard skin rates (14%). The only incident lesions were three subjects
      from a single community having the appearance of new nodules (e.g., nodules not
      identified in the 1995 examinations). Differences in community coverage did not
      appear to influence the benefit from treatment of individual residents.

PMID- 15155992
TI  - West Nile virus in mosquitoes of Northern Ohio, 2001-2002.
AB  - From June 14 to August 30, 2001 and June 10 to August 22, 2002, the mosquitoes of
      Oberlin, Ohio were surveyed and tested for West Nile virus (WNV). Mosquitoes were
      trapped weekly using gravid traps and CO(2)-baited Centers for Disease Control
      light traps at seven sites in 2001 and eight sites in 2002 in woodlots within the
      city limits. A total of 12,151 mosquitoes, representing 14 species and one
      species group, were collected in gravid traps, with Culex pipiens/restuans being
      the most abundant, followed by Ochlerotatus triseriatus. In light traps, 12,510
      mosquitoes were collected, with Aedes vexans being the most abundant, followed by
      Culex pipiens/restuans. All gravid trap collections were tested for WNV via
      reverse transcriptase-polymerase chain reaction. West Nile virus was first
      detected in July 2002. Of all species tested, the Cx. pipiens/restuans species
      group exhibited the highest minimum infection rate (MIR) and the greatest
      percentage of positive pools. Both the MIR and percent of positive pools
      increased significantly with the date, although abundance of Cx. pipiens/restuans
      in gravid trap collections did not.

PMID- 15155993
TI  - Patterns of West Nile virus infection in Ohio blue jays: implications for
      initiation of the annual cycle.
AB  - West Nile virus (WNV) was first detected in North America in New York City in
      1999 and rapidly moved westward. Understanding the mechanisms by which the
      amplification cycle is reinitiated each year increases our ability to predict
      epizootics and geographic expansion of the disease. Such understanding is
      enhanced by knowledge of the patterns of infection in the vertebrate reservoir
      hosts. Blue jays (Cyanocitta cristata) may serve as reservoir hosts for WNV. We
      examined the influence of age and date on the prevalence of WNV in jay carcasses
      in Ohio during May-August 2002. Percent of carcasses that were infected increased
      significantly with time from 3% in May to more than 90% by August. We found no
      difference in prevalence between juvenile (nestlings and fledglings) and adult
      jays early in the season, which contradicts the expected pattern if the majority
      of the adults sampled in 2002 had been exposed to the virus in 2001. Therefore,
      jays infected in 2001 were unlikely to have been important in initiating the 2002
      virus cycle in Ohio.

PMID- 15155994
TI  - Relationship of genotype rather than race to hepatitis B virus pathogenicity: a
      study of Japanese and Solomon Islanders.
AB  - The aim of this study was to determine the predominant hepatitis B virus (HBV)
      genotype in the Solomon Islands and determine if there is any racial correlation
      between genotype and hepatitis B e antigen (HBeAg) production in Japanese and
      Melanesian individuals. A total of 403 serum samples from 206 Melanesian HBV
      carriers in the Solomon Islands and 197 Japanese carriers from Fukuoka (n = 106)
      and Okinawa (n = 91) living in Japan in 2001 were tested. The HBV genotypes of
      206 Melanesian subjects were 114 with genotype C (55.3%) and 92 with genotype D
      (44.7%). The HBV genotypes of 197 Japanese subjects were 74 with genotype B
      (37.6%) and 123 with genotype C (62.4%). The total HBeAg prevalence of subjects
      in Fukuoka (36.8%) was significantly higher than that of subjects in Okinawa
      (14.3%) (P < 0.0001) and subjects in the Solomon Islands (35.0%; P = 0.0014, by
      the Mantel-Haenszel test). The genotype C prevalences were significantly
      different, ranging from 24.2% in Okinawa, to 54.4% in the Solomon Islands, to
      95.3% in Fukuoka (all P < 0.0001, by chi-square test). The prevalence of HBeAg
      positivity was significantly higher in Melanesian genotype C subjects (42.0%)
      than Melanesian genotype D subjects (26.6%) (P = 0.0310). Similarly, the
      prevalence of HBeAg positivity was significantly higher in Japanese genotype C
      subjects (36.6%) than Japanese genotype B subjects (9.5%) (P < 0.0001). These
      findings indicate that that HBV was of genotypes C and D in the Solomon Islands,
      and that the pathogenesis of HBV-infected patients is related to HBV genotype
      rather than race.

PMID- 15155995
TI  - Comparison of the effectiveness of five different antibiotic regimens on
      infection with Rickettsia typhi: therapeutic data from 87 cases.
AB  - This study estimated the clinical effectiveness of five different antibiotic
      regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus
      chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection
      with Rickettsia typhi in terms of the duration of the fever. Eighty-seven
      patients with endemic typhus were hospitalized between 1993 and 1998 at the
      General Hospital of Chania in Chania, Crete, Greece. The mean time to
      defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2
      days for ciprofloxacin. In patients receiving combinations of doxycycline plus
      chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0
      days, respectively. The outcome was favorable in all patients, and no deaths or
      relapses were observed within two months.

PMID- 15155996
TI  - C-reactive protein in the diagnosis of melioidosis.
AB  - Previous work suggested that C-reactive protein (CRP) may be a useful test in the
      diagnosis of melioidosis, the infection caused by Burkholderia pseudomallei. We
      reviewed patients with culture-confirmed melioidosis to define the role of this
      inflammatory marker in the diagnosis of melioidosis. In 175 patients, we found
      that the admission CRP level may be normal or only mildly elevated, including
      patients with severe sepsis, fatal cases, and in relapsed melioidosis. In a
      multivariate analysis, sepsis and bacteremia were more strongly associated with
      mortality than CRP. Admission levels of CRP are not a sensitive marker for the
      presence of melioidosis and a normal level cannot be used to exclude acute,
      chronic, or relapsed melioidosis in febrile patients in or from endemic regions.

PMID- 15155997
TI  - The changing pattern of coronary perforation during percutaneous coronary
      intervention in the new device era.
AB  - We report the incidence, management and clinical outcome of coronary perforations
      in 39 of 12,658 patients (0.3%) undergoing percutaneous coronary intervention
      (PCI). Coronary perforation occurred more frequently with debulking techniques
      than with non-debulking (percutaneous transluminal coronary angioplasty and
      stent) techniques (1% versus 0.2%; p<0.001). There were 8 type I (20.5%), 15 type
      II (38.5%) and 16 type III (41%) perforations. Importantly, fifty-one percent of
      the coronary perforations were guide-wire related. Major adverse clinical
      outcomes occurred more frequently in patients who experienced type III
      perforations. Conventional strategies to treat perforations (i.e., prolonged
      balloon inflation and reverse of the anticoagulated state) were used. There was
      one death (2.6%), two emergency surgeries (5.2%) and no Q-wave myocardial
      infarctions. Pericardial effusion occurred in 18 of 39 patients (46.2%), with
      cardiac tamponade occurring in 7 patients. In the current device era, the
      incidence of coronary perforation remains low; it occurs more frequently with
      debulking devices and is often a consequence of guidewire injury. Its outcome is
      not affected with the use of IIb/IIIa antagonists. Treatment of coronary
      perforation requires early detection, angiographic classification, immediate
      occlusion of coronary vessel extravasation and relief of hemodynamic compromise,
      reversal of heparin anticoagulation, platelet transfusion in those patients
      treated with abciximab and cover stents.

PMID- 15155998
TI  - Coronary perforations: old screenplay, new actors!

PMID- 15155999
TI  - Reduction of subacute stent thrombosis (SAT) using heparin-coated stents in a
      large-scale, real world registry.
AB  - PURPOSE: This study was designed to compare the rates of subacute stent
      thrombosis (SAT) among patients receiving heparin-coated stents to patients
      receiving bare-metal stents in real world, contemporary coronary interventions.
      BACKGROUND: Controlled trials with heparin-coated coronary stents have shown a
      trend toward decreased rates of SAT. METHODS AND RESULTS: The data in this study
      were collected from a single, large cardiac center over a period of 9 months. All
      patients who underwent coronary stent implantation during this 9-month period
      were included in the study (1,288 patients; 1,366 procedures; 2,231 stents). All
      patients were treated with aspirin and clopidogrel (or ticlopidine) after
      stenting. Primary thrombotic outcome was defined as angiographically documented
      SAT and/or sudden unexplained cardiac death (SCD) within 30 days of the
      procedure. Follow-up data (1,264/1,276 patients) were obtained in 99% of
      patients. A total of 337 patients received 543 heparin-coated stents (BX Velocity
      Hepacoat) and 939 patients received bare-metal stents (1,688 stents). SAT was
      seen in 25/1,024 procedures (2.44%) in the bare-metal stent group and 1/342
      procedures (0.29%) in the heparin-coated stent group. Primary thrombotic outcomes
      (SAT or SCD) were observed in 31/1,024 procedures (3.03%) in the bare-metal stent
      cohort and in 2/342 procedures (0.58%) in the heparin-coated stent group. The
      vast majority (96%) of the patients who had SAT within 30 days had initial stent
      placement for an acute coronary syndrome (p<0.0001). CONCLUSION: This large,
      single-center registry demonstrates a significant reduction of SAT using heparin
      coated stents compared to bare-metal stents in real world coronary interventions.

PMID- 15156000
TI  - Clinical outcomes following IVUS-guided stent deployment in a community hospital.
AB  - OBJECTIVES: A discrepancy exists in the medical literature as to what effect
      intravascular ultrasound (IVUS)-guided stent deployment has on target vessel
      revascularization (TVR) at 6 months. The major endpoints of this study are the
      need for TVR, defined as clinically driven repeat interventional or surgical
      therapy of the index vessel at 6 months and major adverse cardiac events.
      METHODS: One hundred interventional stent cases (50 IVUS-guided, 50 non-IVUS
      guided) were randomly selected in a 6-month period (January to June 2001) for
      review by measurement of minimal luminal diameter (MLD) pre- and post
      intervention. Seventy males and 30 females were distributed among the 2 groups.
      There were a total of 135 lesions (70 IVUS-guided, 65 non-IVUS guided) in the 2
      groups. A 6-month follow-up chart review was performed following the initial
      stenting. RESULTS: At 6-month follow-up, there were 2 deaths in the IVUS-guided
      group and 3 deaths in the non-IVUS guided group (p=NS). All deaths were
      cardiovascular in nature. Post-procedure MLD was 3.58+/-0.08 mm for the IVUS
      guided group and 2.88+/-0.09 mm for the non-IVUS guided group [t=5.7 (df, 133);
      p<0.001]. Ten of 70 IVUS-guided lesions (14.3%) and 3 of 65 non-IVUS guided
      lesions (4.2%) underwent TVR within the 6-month study period (Chi square=3.62;
      p=0.057). CONCLUSION: In this population, IVUS-guided stent deployment does not
      appear to reduce either the need for TVR or overall cardiovascular mortality at 6
      months. The added expense of IVUS does not appear to be warranted.

PMID- 15156001
TI  - IVUS-guided stenting: where is the harm?

PMID- 15156002
TI  - Utility of routine functional testing after percutaneous transluminal coronary
      angioplasty: results from the ROSETTA registry.
AB  - BACKGROUND: There is little consensus regarding the use of functional testing
      after percutaneous transluminal coronary angioplasty (PTCA). Some physicians
      employ a routine functional testing strategy, and others employ a symptom-driven
      strategy. OBJECTIVE: To examine the effects of routine post-PTCA functional
      testing on the use of follow-up cardiac procedures and clinical events. METHODS:
      The Routine versus Selective Exercise Treadmill Testing after Angioplasty
      (ROSETTA) Registry is a prospective multicenter observational study examining the
      use of functional testing after PTCA. A total of 788 patients (pts) were enrolled
      in the ROSETTA Registry at 13 clinical centers in 5 countries. The frequencies of
      functional testing, cardiac procedures and clinical events were examined during
      the first 6 months following a successful PTCA. RESULTS: Patients were
      predominantly elderly men (mean age, 61+/-11 years; 76% male) who underwent
      single-vessel PTCA (85%) with stent implantation (58%). During the 6-month follow
      up, a total of 237 pts were observed to undergo a routine functional testing
      strategy (100% having functional testing for routine follow-up), while 551 pts
      underwent a selective (or clinically-driven) strategy (73% having no functional
      testing and 27% having functional testing for a clinical indication). Patients in
      the routine testing group underwent a total of 344 functional tests compared with
      165 tests performed in the selective testing group (mean, 1.45 tests/patient
      versus 0.3 tests/patient; p<0.0001). There was little difference in the rates of
      follow-up cardiac procedures among the pts undergoing the routine and selective
      testing strategies [cardiac catheterization, 13.9% versus 17.5% (p=NS);
      percutaneous coronary intervention (PCI), 8.4% versus 8.7% (p=NS); coronary
      artery bypass graft surgery, 2.1% versus 3.3% (p=NS)]. However, clinical events
      were less common among pts who underwent routine functional testing, e.g.,
      unstable angina (6.1% versus 14.4%; p=0.001), myocardial infarction (0.4% versus
      1.6%; p=NS), death (0% versus 2.2%; p=0.02) and composite clinical events (6.3%
      versus 16.3%; p<0.0001). After controlling for baseline clinical and procedural
      differences, routine functional testing had a persistent independent association
      with a reduction in the composite clinical event rate (odds ratio, 0.45; 95%
      confidence interval, 0.24-0.81; p=0.008). CONCLUSION: Routine functional testing
      after PTCA is associated with a reduction in the frequency of follow-up clinical
      events. This association may be attributable to the early identification and
      treatment of pts at risk for follow-up events, or it may be due to clinical
      differences between pts who are referred for routine and selective functional
      testing.

PMID- 15156003
TI  - To stress or not to stress? That is the question.

PMID- 15156004
TI  - Is a 300 mg clopidogrel loading dose sufficient to inhibit platelet function
      early after coronary stenting? A platelet function profile study.
AB  - BACKGROUND: Clopidogrel combined to aspirin reduces the early risk of stent
      thrombosis and a clopidogrel pre-treatment strategy is associated with a better
      outcome. However, in clinical practice such pre-treatment strategy is not always
      feasible and clopidogrel is frequently not administered until the time of
      intervention. Aim of the study was to compare platelet function profiles in
      patients undergoing coronary stenting receiving clopidogrel pre-treatment (75 mg
      x 2 daily at least 48 hours before intervention) compared to that of patients
      receiving a 300 mg loading dose at intervention time. METHODS: A total of 50
      patients were included in whom patients' platelet aggregation (using light
      transmittance aggregometry) and platelet activation (P-selectin and PAC-1
      expression by whole blood flow cytometry) were assessed following ADP stimuli at
      baseline, and 4 hours and 24 hours following coronary stenting. RESULTS: In the
      overall study population, 16/50 (32%) patients were pre-treated with clopidogrel
      and 34/50 (68%) received clopidogrel loading dose at intervention time. Platelet
      aggregation, as well as P-selectin and PAC-1 expression were significantly lower
      in clopidogrel pre-treated patients at baseline (p<0.001) and at 4 hours
      (p<0.01), while they were similarly inhibited 24 hours after intervention. In
      conclusion, platelet reactivity of patients treated with clopidogrel front
      loading at intervention time remains significantly higher than that of pre
      treated patients in the early hours after coronary stenting. A higher loading
      dose at intervention time may be warranted to overcome the early risk of
      thrombotic complications.

PMID- 15156005
TI  - Successful multi-vessel percutaneous coronary intervention with bivalirudin in a
      patient with severe hemophilia A: a case report and review of literature.
AB  - We describe a 64-year-old male with severe hemophilia A (factor VIII-dependent),
      acute myocardial infarction (MI) and congestive heart failure (CHF) who underwent
      successful multi-vessel percutaneous coronary intervention (PCI). The patient was
      administered factor VIII transfusion to maintain activity levels between 60-80%.
      Anticoagulation during the PCI procedure was maintained with the direct thrombin
      inhibitor, bivalirudin. There were no procedural complications and the patient
      was discharged home the following day. These results suggest that bivalirudin may
      be used effectively in patients at very high risk of bleeding with enhanced
      procedural safety.

PMID- 15156006
TI  - Spontaneous coronary artery dissection: management options in the stent era.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of coronary
      obstruction, usually affecting women in the childbearing age. Pathogenetic
      mechanisms are elusive, and optimal treatment is not established. We describe a
      case of spontaneous coronary artery dissection that was successfully treated by
      coronary stenting. The published literature regarding the outcome of this
      modality of treatment in patients with SCAD is reviewed. A patient with
      spontaneous coronary artery dissection treated by stenting is described along
      with a review of the published literature regarding treatment of similar
      patients.

PMID- 15156007
TI  - Treatment of saphenous vein graft thrombosis with distal protection,
      thrombectomy, and adenosine prior to reperfusion: a complete approach to
      preserving microvascular integrity.
AB  - We report the treatment of an acute myocardial infarction presenting late with
      thrombotic total occlusion of a saphenous vein graft. A novel approach was used
      to prevent microvascular obstruction and reperfusion injury, with a distal
      protection system, a thrombectomy device, and administration of intracoronary
      adenosine prior to restoration of flow, so that initial reperfusion was done with
      maximal microvascular vasodilatation.

PMID- 15156008
TI  - Inappropriate ICD therapy due to electrical interference: external alternating
      current leakage.

PMID- 15156009
TI  - Hypertrophic obstructive cardiomyopathy in the era of cardiac MRI.

PMID- 15156010
TI  - Alveolar hemorrhage associated with periprocedural eptifibatide administration.

PMID- 15156011
TI  - Angiographic demonstration of coronary dethrombosis with eptifibatide.
AB  - When dealing with acute coronary syndromes, the interventionists often go
      straight to balloon and stents, because they work quick and well in the majority
      of cases. However, it is not to forget that vigorous antithrombotic treatment is
      frequently highly beneficial in these settings. We report here on two clinical
      cases of coronary thrombosis in which we could appreciate on the angiograms the
      effect of GP IIb/IIIa inhibitor eptifibatide alone or in conjunction with
      alteplase.

PMID- 15156012
TI  - Can posterior fossa lesions be a place for preventive patent foramen ovale
      transcatheter closure?

PMID- 15156013
TI  - Intravascular ultrasound imaging and percutaneous intervention in a patient with
      post-mitral valve replacement circumflex coronary artery occlusion.

PMID- 15156014
TI  - Detection of tetracycline resistance genes by PCR methods.
AB  - Rapid, accurate, and sensitive determination of antibiotic resistance profiles of
      various human and animal pathogens becomes a vital prerequisite for successful
      therapeutic intervention in the face of the increased occurrences of drug
      resistant bacterial infections. The current methods, which are dependent on
      cultivation of pathogens and phenotypic expression of antibiotic resistance,
      usually require excessive time, special microbiological equipment, and qualified
      personnel. However, even with all these requisites, for example, no bacteria can
      be grown from more than 80% of all clinical samples sent to clinical microbiology
      laboratories. Besides the cultivation limitations, the cultivation-based
      determination of an antibiotic resistance profile lacks the genotypic
      information, which is essential for understanding the epidemiology and routes of
      transmission of antibiotic resistance genes. These genes often reside on mobile
      genetic elements and can move freely between commensal and pathogenic microbiota,
      occurring even between taxonomically distant clinical and environmental
      microbiota. Therefore, development of genotyping methods for detection of
      antibiotic resistance genes is highly desirable for fast, accurate, and sensitive
      detection of antibiotic resistance genes in a broad range of pathogenic and
      commensal bacteria in both clinical and environmental samples. As a model for our
      studies we have chosen the genes conferring resistance to tetracyclines.
      Tetracyclines belong to a family of broad-spectrum antibiotics that include
      tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline,
      doxycycline, minocycline, and a number of other semisynthetic derivatives. These
      antibiotics inhibit protein synthesis in Gram-positive and Gram-negative bacteria
      by preventing the binding of aminoacyl-tRNA molecules to the 30S ribosomal
      subunit. The antibiotics of this group were introduced in the late 1950s and
      since then have been widely used in clinical and veterinary medicine, as well as
      for prophylaxis and growth promotion in food animals. Because of the possible
      misuse and overuse of these drugs, resistance to this class of antibiotics is
      widespread among many clinical isolates, thus limiting the utility of
      tetracyclines in treating infections. Despite this shortcoming, antibiotics of
      this class still remain in the active arsenal for dermatologists to treat skin
      infections such as acne and rosacea.

PMID- 15156015
TI  - Integron analysis and genetic mapping of antimicrobial resistance genes in
      Salmonella enterica serotype Typhimurium.
AB  - Antimicrobial resistance determinants may be transferred among bacteria via
      mobile genetic elements including plasmids, transposons, and the more recently
      explored integrons. Integrons are naturally occurring genetic elements found as
      part of the Tn21 transposon family or located on various broad host-range
      plasmids. The fundamental integron structure consists of a 5'-conserved segment
      (5'-CS) of 1.4-kbp and a 2-kbp 3'-CS. Between these conserved regions are DNA
      sequences of variable length and molecular complexity. These intervening
      sequences are known as gene cassettes, and several have now been characterized.
      Acquisition and dissemination of these genes located within the integron
      structure, results in an increase in antimicrobial resistance. Three classes of
      integron structure have been described. Class 1 integrons are of principal
      importance in clinical isolates. The 5'-CS of class 1 integrons includes an intI
      1 gene of 1358 bp, which encodes a specific recombinase, a member of the DNA
      integrase family. This gene contains the att1 recombination site, required for
      specifically integrating gene cassettes. Classes 2 and 3 also contain integrase
      genes (intI 2 and intI 3), with the former showing 40% sequence identity to those
      of class 1, and the latter showing 61%. All three classes of integrons contain
      similar gene cassettes from the same families, which suggests the existence of a
      common pool of gene cassette with cross-specificity between the classes. When the
      3'-CS region is examined in detail, it contains several open reading frames
      (ORFs). These include qacEDelta1, which confers resistance to quaternary ammonium
      compounds, often associated with antiseptics, along with a sul1 gene expressing
      resistance to sulphonamide antimicrobial agents. The sul1 gene encodes the enzyme
      hydopteroate synthase. Transcription of the sul1 gene begins at a promoter
      located in the 5'-CS. The latter is also responsible for the transcription of the
      inserted gene cassette(s). Two additional ORFs, ORF-5 and -6, are located toward
      the distal end of the 3'-CS. The gene product of ORF 5 appears to share some
      sequence similarity with puromycin acetyltransferase, and this feature suggests a
      possible role in antimicrobial resistance. A biological function has yet to be
      ascribed to ORF-6.

PMID- 15156016
TI  - Molecular-based identification and typing of Campylobacter jejuni and C. coli.
AB  - Thermophilic Campylobacter spp., mainly Campylobacter jejuni and to a lesser
      extent C. coli are recognized as the most common bacteriological causes of
      gastroenteritis in humans. As enteric infection with Campylobacter organisms
      cannot be distinguished from that caused by other enteric pathogens, a definitive
      diagnosis can only be made by isolating or detecting the organism from the feces.
      The epidemiology of Campylobacter enteritis has been complicated by the
      ubiquitous nature of the organism (commonly found as a commensal in the
      intestines of domestic animals, in milk, and in water). Furthermore,
      identification is carried out only to genus level by most clinical laboratories.
      Because of the biochemical similarity known to exist between C. jejuni and C.
      coli, the hippurate hydrolysis test is often used as the only phenotypic test
      capable of differentiating the two species. This test, however, has some
      acknowledged technical limitations and is dependent on inoculum size; results can
      be difficult to interpret accurately. Furthermore, almost all C. jejuni isolates
      possess the hippuricase gene, fewer C. jejuni isolates express the hippuricase
      gene. For this reason, certain polymerase chain reaction (PCR)-based species
      identification methods, for both C. jejuni and C. coli, and for the other
      thermophilic species, provide more reliable identification; they also help to
      highlight mixed species cultures, should they occur. However, even with these
      methods, false negatives or nonspecifically amplified product(s) can occur in a
      minority of isolates tested owing to genomic anomalies. Thus a second molecular
      identification method may be required in these circumstances. Gonzalez et al.
      developed a species-specific PCR assay for the identification of C. jejuni and C.
      coli based on the ceuE gene, which is involved in siderophore transport. Using
      this method two primer sets are employed in separate PCR amplification reactions.
      Another method, developed by Eyers et al., performs PCR amplification of 23S rRNA
      gene fragments, based on regions specific for C. jejuni, C. coli, C. lari, and C.
      upsaliensis. In addition, Hani and Chan developed a PCR assay that detected and
      amplified the hippuricase gene. This molecular approach may offer a more reliable
      means of identifying C. jejuni strains compared with the phenotypic hippurate
      hydrolysis test alone.

PMID- 15156017
TI  - Molecular genotyping methods and computerized analysis for the study of
      Salmonella enterica.
AB  - Salmonella enterica is widely recognized as a major cause of foodborne diseases
      in humans and animals and has been isolated from environmental sources in
      increasing numbers worldwide. Conventional typing methods such as serotyping and
      phage typing have been and still are the mainstay in descriptive epidemiology of
      this microorganism. Nevertheless, limitations on the availability of phage
      reagents circumscribes the performance of such technique in reference
      laboratories. The resolving power of epidemiological typing has been expanded
      during recent years through the molecular analysis of microbial DNA. The broader
      availability of the reagents and equipment is accelerating their generalized use
      in clinical and public health laboratories. Important differences in the
      performance criteria of the genotyping techniques (typability, reproducibility,
      stability, and discriminatory power) and the convenience criteria (flexibility,
      accessibility, and ease of use) exist between them, and there is no ideal typing
      system for universal use. Most of these powerful strain-discriminative techniques
      are based on comparison of electrophoretic patterns or fingerprints, for which
      computer-assisted strategies and software packages have been developed to help in
      construction and analysis of microbial databases. Several initiatives, such as
      PulseNet (http://www.cdc.gov/pulsenet) or Harmony
      (http://www.phls.org.uk/inter/harmony), have arisen during recent years for
      international construction of such fingerprinting databases, which will allow the
      rapid detection of new strains and the spread of pathogenic clones of bacteria
      through different regions or countries. Nevertheless, complete consensus has not
      yet been achieved on the techniques to use or the criteria for interpretation of
      the results, but these goals may be reached soon.

PMID- 15156018
TI  - Detection of infectious rotaviruses by flow cytometry.
AB  - Human rotaviruses are considered the main cause of viral gastroenteritis in
      infants and young children throughout the world. Their transmission is through
      the fecal-oral route, mostly after ingestion of contaminated water and food.
      Since an extremely high number of virus particles are present in the feces during
      the acute gastroenteritis, methods based on electron microscopy, passive particle
      agglutination tests, or enzyme-linked immunosorbent assays are readily employed
      for clinical diagnosis. However, the sensitivity of these procedures is not high
      enough to detect the low number of viral particles sometimes present in the
      environment. In the case of environmental samples, amplification of viral nucleic
      acids by polymerase chain reaction assays coupled to reverse transcription (RT
      PCR) has been increasingly applied to detect rotaviruses in water and shellfish
      samples. However, procedures based on molecular approaches have to face the
      drawback that they do not differentiate between infectious and noninfectious
      particles, which is of major relevance from the public health point of view.
      Virus propagation in cell culture prior to detection by immunological or
      molecular procedures accomplishes the dual purpose of increasing the amount of
      target material and incorporating an infectivity assay as well.Wild-type
      rotaviruses present difficulties in their in vitro replication, although some of
      them may be adapted to grow in several cell lines such as the monkey kidney cell
      line MA104 or the human intestinal cell line CaCo-2. More than a decade ago, an
      assay for the specific detection of infectious rotaviruses in environmental
      samples, involving an indirect immunofluorescence test (IIF) and optical
      microscopy (OM) counting of infected foci in infected MA-104 cell monolayers, was
      described. On the other hand, CaCo-2 cells have been successfully employed in our
      laboratory for infectivity assays of several fastidious enteric virus strains
      present in water samples.

PMID- 15156019
TI  - Integrated cell culture/PCR for detection of enteric viruses in environmental
      samples.
AB  - Recently, an integrated cell culture/polymerase chain reaction (ICC/PCR)
      technique has been developed for the detection of viruses in environmental
      samples providing a reliable method for practical analysis and direct monitoring
      of environmental samples for viral pathogens. CC/PCR allows for detection of
      infectious viruses in hours to days compared with the days or weeks necessary
      with cell culture alone. Bacterial indicator organisms are commonly used to
      evaluate environmental samples with respect to fecal contamination and potential
      public health impacts. These organisms do not correlate well with the presence of
      viruses, but a rapid, reliable method was not previously available for direct
      virus testing. Using ICC/PCR, environmental samples may be directly surveyed for
      pathogenic viruses, in a timely manner. Direct virus analysis will lead to better
      assessment of the presence and risk of human enteric viruses in the environment,
      so that control measures may be developed with true virus occurrence data. The
      ICC/PCR approach combines two previously applied virus detection methods,
      conventional cell culture and PCR amplification, utilizing the major advantages
      and overcoming the major limitations of each methodology when used alone. Cell
      culture assay is the standard method for the detection of viable human viruses
      (i.e., poliovirus, coxsackievirus, echovirus, adenovirus, hepatitis A virus,
      reovirus, and rotavirus) in environmental samples, serving as the method against
      which all newer technologies are evaluated. Although cell culture is
      theoretically capable of detecting a single viable virus in relatively large
      volumes of sample, the time required for confirmed results with conventional cell
      culture makes it an impractical method for routine monitoring of environmental
      samples. Furthermore, cell culture does not detect noncytopathogenic viruses
      (viruses that are viable, infecting cells, and continually spreading to
      neighboring cells but that do not cause a visible cytopathogenic effect [CPE] on
      the cell monolayer). Rotavirus and most wild-type hepatitis A viruses (HAV) are
      infectious to cell cultures but do not produce a clear CPE.

PMID- 15156020
TI  - Abundance in sewage of bacteriophages infecting Escherichia coli O157:H7.
AB  - Bacterial virulence factors such as toxins are often encoded by bacteriophages.
      Among other examples, factors encoded by phages have been described in some of
      the emerging or re-emerging pathogens, including the pyrogenic exotoxin A
      production in group A streptococci, the cholera toxin in Vibrio cholerae, or
      enterotoxin production in enterohemorrhagic (EHEC) strains of E. coli. Most
      described virulence factors in Shiga toxin (Stx)-producing E. coli strains are
      located in mobile genetic elements such as plasmids and bacteriophages. Stx,
      which are one of the most important virulence elements in Shiga toxin-producing
      E. coli (STEC), are encoded in the genome of temperate bacteriophages infecting
      E. coli and other Enterobacteriaceae. Studies on Stx phages indicate that they
      are transmitted between different bacteria in vivo and in vitro. Phages could
      also be transmitted extraintestinally, hence the observed presence of infectious
      Shiga toxin phages in sewage and in fecally contaminated rivers. Stx phages also
      show a higher persistence under natural inactivation and disinfectant treatments
      in aquatic environments.This background shows that phages or lysogenic strains
      carrying Stx2 phages might be the natural reservoir of Stx2 genes and that
      lysogenization could be the main cause of the emergence of STEC strains, as
      suggested by several authors. It has also been suggested that
      lysogenization/conversion processes could take place in food and water and
      probably inside the human and animal gut. Ingestion of Stx2 phages could produce
      conversion of non-Stx2-E. coli strains, present inside the gut and producing new
      pathogenic strains. To control these phenomena, it is first necessary to gain
      more information about the distribution of Stx phages in the environment. For
      this purpose, a method of detecting Stx2 phages present in environmental water
      samples has been developed. The particularity of this method is that it allows
      detection of all (infectious and noninfectious) Stx2 phages in a water sample; in
      a second stage, the method allows detection of those phages able to infect and
      replicate on E. coli O157:H7. Although this method has been applied to Stx2
      phages able to infect E. coli O157:H7, it is also applicable to detection in the
      natural environment of other genes carried by other bacteriophages and other
      bacteria.

PMID- 15156021
TI  - Molecular genotyping of Irish rotavirus strains.
AB  - Rotavirus is the primary etiological agent of gastroenteritis in infants and
      young children worldwide. In developing countries, it is estimated that rotavirus
      is responsible for one-third of all diarrhea-associated hospitalizations and
      873,000 deaths annually. In industrialized countries, where mortality from
      rotavirus is low, infection is widespread, and nearly all children experience an
      episode of rotavirus diarrhea in the first 3-5 yr of life. Rotaviruses have
      important antigenic specificities including serogroup and serotype, and all
      viruses are classified accordingly. They are divided into seven morphologically
      indistinguishable but antigenically defined serogroups, delineated A through G.
      The human infecting rotaviruses include groups A, B, and C, and it is well
      documented that group A rotaviruses are the major causative agents of diarrheal
      diseases in children. They are responsible for 125 million cases of diarrhea
      annually. Within each serogroup, distinct serotypes exist. In group A rotavirus,
      serotype is specified by two viral proteins, VP4 and VP7. The neutralizing
      antibody response that is evoked by the antigenic determinants on VP4 and VP7
      play an important role in protective immunity. The rotavirus genome consists of
      11 double-stranded (ds) RNA segments, and each genomic segment encodes a
      different protein. A dual system of reporting rotavirus serotype exists because
      the VP4 and VP7 proteins are encoded by different genes and thus can segregate
      independently. The serotypes derived from VP7 are defined as G-serotypes.
      Currently 14 G-serotypes have been identified, and only 10 of these have been
      recovered from humans. The predominating G-types worldwide are G1, G2, G3, and
      G4, with G1 being the most prevalent type. Serotypes G5, G6, G8-G10, and G12 are
      rarely identified in humans and are usually recovered from animals. However, some
      of these unconventional types are now being frequently reported in humans,
      including G5, G8, and G9.

PMID- 15156022
TI  - Hepatitis a virus: molecular detection and typing.
AB  - Hepatitis A virus (HAV) infection is the leading cause of viral hepatitis
      throughout the world. HAV infection is mainly propagated via the fecal-oral
      route, and waterborne and foodborne outbreaks of the disease have been
      reported.HAV, the prototype of the genus Hepatovirus, belongs to the family
      Picornaviridae. Its 7.5-kb single-stranded RNA genome bears different distinct
      regions: the 5' and 3' noncoding regions (NCR), the P1 region, which encodes the
      structural proteins VP1, VP2, VP3, and a putative VP4, and the P2 and P3 regions
      encoding nonstructural proteins associated with replication. A single HAV
      serotype has been described, although seven genotypes have been defined. Since
      environmental samples usually contain low numbers of viral particles, sensitive
      methods such as molecular techniques based on nucleic acid amplification are
      required for their detection. However, even with the adoption of these
      techniques, the choice of the most adequate target is of relevant importance. The
      target region should be highly conserved, to increase the chance of detection,
      and should have an appropriate structure and length to allow sensitivity high
      enough for these kind of samples. As a target region, we have chosen a fragment
      of the 5'NCR flanked by highly conserved sequences that have been used for the
      primer design (forward primer from position 68 to position 85; reverse primer
      from position 222 to position 240 in the HM175 strain of HAV; GenBank accession
      number M14707). The internal part of this region, however, may present a certain
      degree of variation mainly owing to insertions and/or deletions, causing a
      variable size of the amplimer obtained, i.e., the wild-type HM175 strain gives a
      size of 174 bp whereas the cell-adapted pHM175 strain gives a size of 186 bp. For
      this reason it is extremely important to include a confirmative method such as
      Southern blot hybridization with an internal probe from a region not affected by
      the insertions/deletions.

PMID- 15156023
TI  - Typing fungal isolates: molecular methods and computerized analysis.
AB  - Infections caused by fungi (mycoses) are increasingly reported in many countries
      owing to greater life expectancy associated with an increase in quality of
      medical and surgical procedures, as well as the emergence of diseases or
      infections that affect the immune system such as AIDS. Nosocomial outbreaks of
      fungal infections are sometimes reported, and typing is then necessary to find
      the reservoirs, analyze the modes of transmission, study the antifungal
      susceptibility patterns, and investigate the susceptibility of the host. In
      addition, the food industry is increasingly demanding typing methods that could
      help in selection of the best fungal strains, in order to incorporate them in the
      productive chains and augment the quality and security of food. This is the case
      for Saccharomyces cerevisiae in the wine industry: the selection and
      characterization of indigenous or autochthonous strains is an important objective
      for the production of high-quality certified wines.Several genotyping methods are
      now widely used for strain delineation of medically or economically important
      microorganisms belonging to the kingdom Fungi. Most molecular typing methods are
      comparable to those already described for bacteria, although the peculiarities of
      their nucleic acids increase the number of available methods. Although typing
      procedures based on the analysis of nucleic acid sequences have been developed,
      most genotyping methods currently in use are electrophoretically based, and the
      procedures include the visual comparison of nucleic acid band profiles or their
      reading with the help of computerized software. Here we describe some of the most
      frequently used genotyping methods for fungi, based on polymerase chain reactions
      (PCR), the isolation of chromosomal or mitochondrial DNA, and their restriction
      using endonuclease enzymes. The latter methods are exclusive for typing
      eukaryotic organisms and are based on the expected polymorphism obtained from the
      separation of large chromosomes using pulsed-field gel electrophoresis (PFGE) and
      the restriction of mitochondrial or chromosomal DNA. More sophisticated methods,
      such as those that combine endonuclease restriction with hybridization, are also
      available, although their use is less extensive and is limited mostly to research
      laboratories.

PMID- 15156024
TI  - Fungal isolation and enumeration in foods.
AB  - Humans have now been growing and storing enough food for a long enough time that
      some rapidly evolving organisms, such as fungi, are moving into niches created by
      the exploitation of certain plants as food. Food is expected to be nutritious.
      The most important of the physicochemical conditions that affects fungal growth
      is related to the biological state of the food. Living foods, particularly fresh
      fruits, vegetables, and also grains and nuts before harvest, possess powerful
      defense mechanisms against microbial invasion. When the specific microorganisms
      overcome defense mechanisms, the spoilage of a living food starts. Other factors
      to consider are water activity, hydrogen ion concentration, temperature, gas
      tension, consistency, nutrient status, specific solute effect, and preservation.
      The consequences of mold contamination of foods are diverse: unsightly
      appearance, chemical (removal or change of most of the constituents) and
      nutritional value changes, modification of organoleptic quality, difficulties in
      preservation, occupational hazards (mycoses, allergies), and toxicoses
      (mycotoxicoses). It is possible to recognize a succession of three distinct
      mycoflora during the storage of cereals, but they can also be mixed: 1. Field
      fungi growing and established before harvesting (Alternaria, Fusarium,
      Helminthosporium, Cladosporium). 2. Storage fungi taking over and dominanting in
      the silo (Aspergillus and Penicillium). 3. Advanced decay fungi (Papulospora,
      Sordaria, Fusarium graminearum, and members of the order Mucorales).

PMID- 15156025
TI  - Determination of aflatoxins and zearalenone in different culture media.
AB  - Some molds produce desirable changes in food, but most are merely esthetically
      undesirable. There has also been an increasing awareness that certain metabolic
      products of some molds commonly found on foods and feed are dangerous to humans
      and animals. These toxin substances, mycotoxins, are secondary metabolites
      produced by different fungi, especially Aspergillus, Penicillium, Fusarium, and,
      to a lesser degree, Alternaria. The most important toxins for humans are
      aflatoxins, ochratoxin A, fumonisins, certain trichothecenes, and zearalenone.
      Aflatoxins are fungal metabolites produced by different Aspergillus species: A.
      flavus, A. parasiticus, and A. nomius. The most commonly encountered aflatoxins
      are B1, B2, G1, G2, M1, and M2, but aflatoxin B1 is the most frequently found in
      contaminated samples, and aflatoxins B2, G1, and G2 are generally not reported in
      the absence of AFB1. The International Agency for Research on Cancer (IARC)
      considers that aflatoxins are carcinogenic (hepatocarcinogenic) to humans (group
      1) and animals. Zearalenone is an estrogenic mycotoxin produced by several
      species of Fusarium (F. acuminatum, F. culmorum, F. equiseti, F. graminearum, F.
      verticilliodes, F. oxysporum, F. poae, F. rosum, F. solani, F. semitectum, and F.
      sporotrichioides) that primarily colonize different cereal grains. Several
      reports were noted on the occurrence of ZEA along with various combinations of
      group B trichothecenes, fumonisins, aflatoxins, and ochratoxins. In most cases,
      the levels of ZEA were considered to be low; however, the toxicological
      significance is not known. This toxin is not classifiable as to carcinogenicity
      in humans (group 3) by the IARC, but ZEA was implied in precocious sexual
      development in children in Puerto Rico and a breast enlargement in young boys in
      Italy.

PMID- 15156026
TI  - Intracellular multiplication of Legionella species and the influence of amoebae
      on their intracellular growth in human monocytes: mono mac 6 cells and
      Acanthamoeba castellanii as suitable in vitro models.
AB  - Legionellae are important etiological agents of pneumonia. Legionella pneumophila
      (predominantly serogroup 1) is detected in most cases of legionellosis; other
      species only occasionally cause infections, predominantly in immunocompromized
      patients. Aquiferous technical systems are the primary source of infection (air
      conditioning systems, refrigerators, showers, whirlpools, springs, taps,
      moisturizing equipment, medical nebulizers, and swimming pools). Legionellae are
      present in the water in these systems, within the amoebae, flagellates, and
      ciliates in which they replicate. After inhalation of contaminated aerosols, the
      bacteria multiply intracellularly within alveolar macrophages. The ability to
      multiply within monocytic host cells is usually considered to correspond to
      pathogenicity. The mechanisms of intracellular replication have been only
      partially characterized. Analysis of the molecular pathogenesis of Legionella
      infection, both in the pathogen itself and in the host cell, is the subject of
      current research and may lead to new options in prophylaxis and treatment. We
      have established the human Mono Mac 6 cell line (MM6) instead of the previously
      used histiocytic lymphoma cell line U 937 or the promyelocytic leukemia cell line
      HL-60 to investigate the intracellular replication of legionellae and the
      molecular pathogenesis of Legionella infection within human monocytic host cells.
      MM6 cells represent a more mature macrophage-like cell line that expresses
      phenotypic and functional properties of mature monocytes and that does not need
      to be stimulated by phorbol esters or 1,25-dihydroxyvitamin D3. A good
      correlation between the prevalence of a given Legionella species and its
      intracellular multiplication in MM6 cells could be demonstrated.In addition to
      Legionella, MM6 cells were found to support the intracellular growth of
      Mycobacterium tuberculosis and Chlamydia pneumoniae, two other important
      bacterial agents involved in induction of pneumonia. Therefore, the MM6 model
      might be adaptable to investigations of the molecular pathogenesis of other
      intracellular bacteria that can replicate within human monocytes and induce
      disease.

PMID- 15156027
TI  - Viability of amoebae, fungal conidia, and yeasts: rapid assessment by flow
      cytometry.
AB  - Conventional methods for the evaluation of antimicrobials and disinfecting
      solutions with microorganisms involve culture-based techniques, which are time
      consuming and underestimate the number of viable organisms. Rapid detection and
      viability measurements of microorganisms in homogenous and heterogenous microbial
      populations have been greatly enhanced by recent advances in the use of
      fluorescent stains in flow cytometry (FCM). FCM has been applied to enumerate,
      differentiate, and identify microorganisms, determine protein and DNA content of
      cells, analyze the physiological state of individual cells, and analyze the
      interaction of drugs, antibiotics, and antimicrobials with microbial cells. Four
      physiological states of cells can be distinguished by FCM: (1) reproductively
      viable, (2) metabolically active, (3) intact, and (4) permeabilized.FCM permits a
      rapid and quantitative measurement of the optical characteristics of cells as
      they pass through, in a single file, a focused beam of light. As cells are
      carried within a fast-flowing fluid stream and through the focus of exciting
      light, three parameters are measured: forward angle light scatter, side angle
      light scatter, and fluorescence emitted by dyes that have specific interaction
      with intracellular components of individual cells. FCM data that are presented in
      histogram and dot plots can be generated to give information on a variety of
      properties of interest among cells in the population as a whole.FCM offers major
      advantages in multiparameter data acquisition and multivariate data analysis,
      high-speed analysis, and cell-sorting capabilities. Disadvantages may be
      associated with the cost, which is usually over 100,000 (US Dollars) for a
      typical laser-based flow cytometer with just analyzing capabilities. Another
      disadvantage is that skilled personnel are usually required to operate these
      complex instruments so as to get optimum performance. A schematic overview of
      flow cytometry is presented in Fig. 1.

PMID- 15156028
TI  - Detection and differentiation of Cryptosporidium oocysts in water by PCR-RFLP.
AB  - Consumption of contaminated water has been implicated as a major source of
      Cryptosporidium infection in various outbreak investigations and case control
      studies. Surveys conducted in various regions of the United States demonstrated
      the presence of Cryptosporidium oocysts in 67-100% of wastewaters, 24-100% of
      surface waters, and 17-26.8% of drinking waters. The identity and human infective
      potential of these waterborne oocysts are not known, although it is likely that
      not all oocysts are from human-infecting Cryptosporidium species. Likewise, the
      source of the oocyst contamination is also not fully clear. Farm animals and
      human sewage discharge are generally considered to be the major sources of
      surface water contamination with C. parvum. Because Cryptosporidium infection is
      common in wildlife, it is conceivable that wildlife can also be a source for
      Cryptosporidium oocysts in waters. The presence of host-adapted Cryptosporidium
      spp. and genotypes makes it possible to develop molecular tools to assess the
      human infection potential and source of Cryptosporidium oocysts in
      water.Currently, the identification of Cryptosporidium oocysts in environmental
      samples is largely made by the use of immunofluorescent assay (IFA) after
      concentration processes (Environmental Protection Agency [EPA] recommended
      information collection rule [ICR] method or method 1622/1623 or similar
      techniques). Because IFA detects oocysts from all Cryptosporidium parasites, the
      species distribution of Cryptosporidium parasites in environmental samples cannot
      be assessed. Although many surface water samples contain Cryptosporidium oocysts,
      it is unlikely that all these oocysts are from human-pathogenic species or
      genotypes, because only five genotypes of Cryptosporidium parasites (the C.
      parvum human and bovine genotypes, C. meleagridis, C. canis, and C. felis) are
      responsible for most human infections. Information on the source of C. parvum
      contamination is necessary for effective evaluation and selection of management
      practices for reducing C. parvum contamination of surface water and the risk of
      cryptosporidiosis. Thus, identification of oocysts to species and genotype levels
      is of public health importance.

PMID- 15156029
TI  - Genotyping of Cryptosporidium parvum with microsatellite markers.
AB  - Recent outbreaks of cryptosporidiosis caused by Cryptosporidium parvum in the
      United States and other countries, as well as the emergence of cryptosporidiosis
      as a frequent cause of morbidity and mortality in immunodeficient individuals,
      have raised the interest of the research community in this parasite. The genus
      Cryptosporidium, phylum Apicomplexa, comprises an undefined number of species, of
      which only C. parvum is of public health concern. Cryptosporidiosis is contracted
      through the ingestion of oocysts, the stage of the parasite produced in large
      numbers by infected hosts. Because the oocysts are small, typically about 5
      microm in diameter, and lack species-specific morphological features, there is a
      need for molecular markers to distinguish between human-infectious C. parvum and
      other species that do not (or only infrequently) cause disease in humans. Genetic
      characterization of Cryptosporidium oocysts using restriction fragment length or
      sequence polymorphism has revealed host-associated genotypes, that are often
      referred to as species. In addition, C. parvum was found to include two
      genotypes, designated type 1 and type 2. Type 1 is almost exclusively found in
      humans, whereas type 2 infects humans and various mammalian hosts. The frequent
      occurrence of Cryptosporidium oocysts in untreated surface water and the
      potential for contamination of drinking water have emphasized the need for
      molecular markers to track the source of oocysts within a watershed or water
      distribution system, and to discriminate between oocysts infectious to humans and
      nonpathogenic species. Genetic markers are also needed to study the taxonomy of
      Cryptosporidium. Several laboratories have identified microsatellites in the
      genome of C. parvum and have investigated the level of polymorphism at these
      loci. For instance, 10 alleles of marker 5B12 have been found to date among C.
      parvum isolates from various geographical and host origins. Multilocus haplotypes
      based on such markers are suitable for discriminating individual isolates of C.
      parvum. In an attempt to develop rapid and cost-effective methods for typing
      isolates of C. parvum, we have pursued two methods, a traditional polymerase
      chain reaction (PCR) method followed by gel electrophoresis, and real-time PCR
      using SYBR Green I melting curve analysis for allele identification.

PMID- 15156030
TI  - Immunomagnetic separation of pathogenic organisms from environmental matrices.
AB  - One of the most difficult challenges in the analysis of environmental samples is
      to separate the organism of interest from a sample that is high in background
      debris. Immunomagnetic separation (IMS) is one technique that has been developed
      to accomplish this in a rapid and reliable assay. Immunomagnetic separation (or
      biomagnetic separation) involves a superparamag-netic, monodispersed, polystyrene
      microsphere that is coated with a specific ligand. When added to a heterogeneous
      target suspension, the microspheres bind to the desired target. Using a powerful
      magnet, the microsphere-target complex is then removed from the suspension. Many
      different targets of interest can be isolated with this technique, including
      fungal/bacterial cells or spores, protozoan parasites, cellular and subcellular
      material, proteins, and nucleic acid products. This wide range of application
      makes IMS one of the most versatile techniques available for the purification of
      target products from heterogeneous sample matrices.

PMID- 15156031
TI  - Detection of Erysipelothrix rhusiopathiae in clinical and environmental samples.
AB  - Erysipelothrix rhusiopathiae is pathogenic for both animals and humans, causing
      erysipelas in swine and erysipeloid in humans. In swine, disease may be either
      acute or chronic, resulting in the development of arthritis and endocarditis. In
      Japan, erysipelas remains an animal hygiene problem causing great economic loss
      as infected swine are disused. Human infection closely resembles that seen in
      swine, with both acute and chronic forms also. The most common presentation is
      erysipeloid, a localized cutaneous infection. In Western Australia, an
      erysipeloid-like infection referred to as "crayfish poisoning" occurs in lobster
      fishermen and handlers. A second type of presentation is a generalized cutaneous
      form involving lesions that progress from the initial site of infection or appear
      in remote areas. The third and most serious form of disease is a septicemia that
      is almost always linked to endocarditis. The mortality rate in Erysipelothrix
      endocarditis is still high (38%) and can be explained by the use of vancomycin
      (to which Erysipelothrix spp. are inherently resistant) as empirical therapy.
      Therefore, it is critical to have an early diagnosis of E. rhusiopathiae
      infection.Unfortunately, several problems exist with the diagnosis of E.
      rhusiopathiae infections by conventional cultural procedures, and these
      infections are often incorrectly diagnosed. First, because of their very small
      colony size and slow growth rates, it is difficult to isolate E. rhusiopathiae
      from heavily contaminated specimens. Various selective media have been described
      to improve the isolation of E. rhusiopathiae from contaminated specimens;
      however, not all contaminants are inhibited. The development of two polymerase
      chain reaction (PCR) methods has created an opportunity to greatly improve the
      efficiency with which these organisms are detected and identified. Makino et al.
      designed a PCR method that amplifies a 407-bp DNA fragment derived from the 16S
      rRNA coding sequence. The primers in this method are specific for the genus
      Erysipelothrix and do not differentiate between the species. A second set of
      primers designed by Shimoji et al. amplifies a 937-bp DNA fragment which is
      derived from a sequence associated with virulence of E. rhusiopathiae. These
      primers are specific for E. rhusiopathiae only. Shimoji et al. also utilized a
      selective enrichment medium based on tryptic soy broth containing ethidium
      bromide and sodium azide.

PMID- 15156032
TI  - Interaction between lactic acid bacteria and gastrointestinal nematodes of
      caprine origin.
AB  - To compare the level of parasitism with gastrointestinal nematodes in sheep and
      goats, several studies have been conducted. They have generally shown that goats
      were more infected than sheep, as they exhibited higher worm burdens and egg
      excretion. This difference between two host species has been attributed not only
      to a difference in feeding behavior, but also to a lesser ability of goats to
      develop resistance to trichostrongylate infection (In kids and lambs the greatest
      damage is observed from weaning until 1 yr of age; mature mothers, before and
      after parturition and during suckling, are affected). In the last few decades,
      the most common tool (and frequently the only one) used for controlling internal
      parasites in livestock was the anthelmintic drugs. The application of
      anthelmintic treatments; must be accompanied by epidemic data and determinations
      supporting the appropriate timing and frequency of animal treatment. This view
      has not always been respected. In our country, because of a decrease in price,
      the anthelmintic drugs were used indiscriminately, causing the resistance we see
      today. This serious problem, added to the objective of producing organic foods
      without drug residuals, calls for better use of the antiparasitic drugs and for
      the developmentment of alternative methods that are ecologically viable and
      without risks for human health.Little information is available on the
      interactions between bacteria and intestinal nematodes of caprine origin. Some
      reports note ovicidal activity of different strains of Bacillus thuringiensis on
      the eggs of zooparasitic nematodes. Recent work found inhibitory actions of
      lactic bacteria on gastrointestinal nematodes (both of caprine origin). In the
      present chapter we describe the methods used for the determination of
      interactions between lactic acid bacteria and nematodes.

PMID- 15156033
TI  - Molecular detection of genes responsible for cyanobacterial toxin production in
      the genera Microcystis, Nodularia, and Cylindrospermopsis.
AB  - Cyanobacteria are ubiquitous in the freshwater environment. Their success as a
      group in a wide range of aquatic habitats has been attributed to their unique
      physiological characteristics and their high adaptive ability over a wide range
      of environmental conditions. They are capable of reaching very high biomass
      levels, often dominating the other aquatic biota, and under some circumstances
      can accumulate near the water surface, producing scums. Such cyanobacterial
      "blooms" are of particular concern in reservoirs used to supply potable water.
      Dense aggregations of cyanobacterial cells may block water filters, and many
      species produce compounds that affect the taste and odor of water supplies. Of
      greatest concern, however, is the potential of many bloom-forming cyanobacteria
      to produce a wide range of toxic substances. These natural compounds, known as
      cyanotoxins, are chemically diverse and are usually either neuro- or hepatotoxic
      in pathology.

PMID- 15156034
TI  - Purification of antilisterial bacteriocins.
AB  - In recent years, numerous contamination outbreaks, involving various pathogens
      (i.e., Listeria and Salmonella), have increased concern over food preservation.
      Research efforts have focused on the discovery of new molecules targeting such
      foodborne pathogens and therefore able to inhibit and or kill them. Lactic acid
      bacteria (LAB) extensively used in fermented foods for thousands of years not
      only improve their flavor and texture but also inhibit pathogenic and spoilage
      microorganisms. LAB inhibitory activity is primarily owing to pH decrease and
      competition for substrates. Antagonistic activity of LAB also depends on secreted
      antimicrobial compounds with a poor selectivity, such as metabolic compounds
      (i.e., hydrogen peroxide, acetoin, and others) or more specific ones like
      bacteriocins. The latter are proteinaceous compounds, ribosomally synthesized and
      subsequently secreted by Gram-positive as well as Gram-negative bacteria. Their
      antimicrobial activity is generally restricted to strains phylogenetically
      related to the producers.A classification of bacteriocins produced by LAB was
      first proposed by Klaenhammer in 1993 and was modified by Nes et al. in 1996;
      class I and class II bacteriocins are the most abundant and thoroughly studied.
      Bacteriocins from both classes exhibit antilisterial activity. Class I
      bacteriocins, namely, lantibiotics, have been widely studied, and among them,
      nisin is used in many countries as a preservative in food products. These
      bacteriocins are characterized by the presence, in their primary structure, of
      post-translationally modified amino acid residues (i.e., lanthionine and
      methylanthionine) that are formed. Class II bacteriocins, containing three
      subclasses, consist of small peptides that do not bear any modified amino acid
      residue. The most studied subclass corresponds to class IIa, also termed anti
      Listeria bacteriocins. These peptides share strong structural homologies in their
      N-terminal domain, with the presence of one disulfide bond and a net positive
      charge. Their C-terminal domain is more variable but appears quite hydrophobic.
      Moreover, some of these bacteriocins, namely, sakacin G, pediocin PA-1, enterocin
      A, coagulin, and divercin V41, are characterized by the presence of a second
      disulfide bond in the C-terminal region.

PMID- 15156035
TI  - The hazard analysis and critical control point system in food safety.
AB  - The Hazard Analysis and Critical Control Point (HACCP) system is a preventive
      method of ensuring food safety. Its objectives are the identification of consumer
      safety hazards that can occur in the production line and the establishment of a
      control process to guarantee a safer product for the consumer; it is based on the
      identification of potential hazards to food safety and on measures aimed at
      preventing these hazards. HACCP is the system of choice in the management of food
      safety. The principles of HACCP are applicable to all phases of food production,
      including basic husbandry practices, food preparation and handling, food
      processing, food service, distribution systems, and consumer handling and use.
      The HACCP system is involved in every aspect of food safety production (according
      to the UN Food and Agriculture Organization [FAO] and the International
      Commission on Microbiological Specifications for Foods [ICMSF]). The most basic
      concept underlying the HACCP system is that of prevention rather than inspection.
      The control of processes and conditions comprises the critical control point
      (CCP) element. HACCP is simply a methodical, flexible, and systematic application
      of the appropriate science and technology for planning, controlling, and
      documenting the safe production of foods. The successful application of HACCP
      requires the full commitment and involvement of management and the workforce,
      using a multidisciplinary approach that should include, as appropriate, expertise
      in agronomy, veterinary health, microbiology, public health, food technology,
      environmental health, chemistry, engineering, and so on according to the
      particular situation. Application of the HACCP system is compatible with the
      implementation of total quality management (TQM) systems such as the ISO 9000
      series.

PMID- 15156037
TI  - Nontraditional method of evaluating disinfectants: with isolated microorganisms
      from the food factory.
AB  - Cleaning and disinfection in the food industry are critical in the production
      process, and the efficacy of the disinfectants used is frequently debated.
      Several factors are involved in the effectiveness of a disinfectant agent. It is
      important to consider the number and type of microorganism present as well as the
      physical and chemical characteristics of the water; these factors vary from
      industry to industry and they determine efficacious disinfection. In the
      laboratory it is possible to evaluate disinfectants to be used in a particular
      factory, even though these are different from those reported by international
      organizations. Some useful practices are: 1. To use cultures of microorganisms
      isolated in one's own lab instead of reference cultures. 2. To use as a diluter
      the water that is used daily in the factory under question. 3. To compare
      different disinfectant products under identical conditions of time and
      temperature.

PMID- 15156036
TI  - Testing disinfectants in the food factory: phenol coefficient method.
AB  - Contamination of foods by the environment has direct public health and keeping
      quality significance. The food factory environment (with raw materials and
      processing) governs the numbers and types of microorganisms in finished products.
      Use of the appropriate sampling procedures permits us to discover the magnitude
      and type of contamination. Microbiological sampling allows objective evaluation
      of the disinfectants and the sanitation practices and procedures used in the food
      factory.Disinfectants are antimicrobial pesticides that are primarily used on
      inanimate surfaces (such as floors, walls, and countertops) to kill infectious
      bacteria, fungi, and viruses. Antimicrobial pesticides are substances used to
      kill or suppress the growth of harmful microorganisms on inanimate objects and
      surfaces. Products intended for the control of microorganisms in or on people or
      animals are considered drugs, not pesticides, and are therefore regulated by the
      Food and Drug Administration (FDA). Antimicrobial pesticides are divided into two
      broad use categories: 1. Non-public health products include those used to control
      the growth of algae, odor-causing bacteria, and microorganisms causing spoilage,
      deterioration, and fouling of materials. Examples include antimicrobials used in
      cooling towers, paints, and paper products. 2. Public health products are
      intended to control microorganisms infectious to people. Examples include
      sterilants, which are used to destroy or eliminate all forms of microbial life
      including fungi, viruses, and all forms of bacteria and their spores;
      disinfectants, which are used to destroy or irreversibly inactivate infectious
      fungi and bacteria, but not necessarily their spores; and sanitizers, which are
      used to reduce, but not necessarily eliminate microorganisms. Examples range from
      sterilants used to treat surgical instruments to disinfectants applied to
      hospital floors, walls, and bed linens and sanitizers used on carpets or in
      laundry additives.

PMID- 15156038
TI  - Microbiological analysis of cosmetics.
AB  - Cosmetics are products of chemical or natural origin dedicated specifically for
      use in skin and mucosa. The constant development of the cosmetic industry has
      generated the necessity to carry out microbiological analysis on the raw
      materials used in the industrial production of cosmetics as well as the final
      products, with the purpose of obtaining products of good microbiological quality.
      Cosmetic products are recognized to be substrates for the survival and
      development of a large variety of microorganisms, since they possess some of the
      nutrients that facilitate growth such as: lipids, polysaccharides, alcohol,
      proteins, amino acids, glucosides, esteroids, peptides, and vitamins. Also, the
      conditions of readiness (oxygenation, pH, temperature, osmotic degree,
      superficial activity, perfume, and essential oils) present in the cosmetic
      products favor microbial multiplication. Routine analyses to determine the
      microbiological quality of a cosmetic product include the following: Count of
      mesophilic aerobic microorganisms. Most probable number (MPN) of total coliforms.
      Count of molds and yeasts. Absence/presence of Staphylococcus aureus probe.
      Absence/presence of Pseudomonas aeruginosa probe.

PMID- 15156039
TI  - Helicobacter pylori and food products: a public health problem.
AB  - Helicobacter pylori is a major human pathogen causing gastritis and chronic
      superficial infection (CSG). It colonizes the stomach of more than 50% of humans
      and causes disease. This microorganism is associated with the gastric antral
      epithelium in patients with active chronic gastritis, peptic (gastric) or
      duodenal ulcers, and gastric adenocarcinoma H. pylori is present in feces,
      sewage, and water but is killed by routine chlorination. Therefore, in developing
      countries, consumption of sewage-contaminated drinking water and vegetables may
      pose a risk; properly cooking foods and chlorinating water reduces the risk of
      transmitting H. pylori to humans. In South America the consumption of raw
      vegetables fertilized with human feces has been found to be a risk factor for
      infection, and consumption of water from a municipal supply has been suggested as
      a risk factor for children. Epidemiological studies have found that H. pylori
      organisms colonize the stomach and duodenum of humans and many animal species and
      family clusters; it is believed to be orally transmitted person to person. This
      transmission is the major, if not exclusive, source of infection.H. pylori has
      been detected in the mouth from dental plaque. Recent observations in persons
      infected with H. pylori caused to vomit or have diarrhea showed that an actively
      unwell person with these symptoms could spread H. pylori in the immediate
      vicinity by aerosol, splashing of vomitus, infected vomitus, and infected
      diarrhea. In summary, H. pylori is usually spread by the fecal-oral route but
      possibly also by the oral-oral route and the spread of contaminated secretions.
      Thus, in developing countries, individuals catch H. pylori at a very young age
      from other persons (children) in their environment. In developed countries, H.
      pylori is more difficult to acquire and is usually transmitted from one family
      member to another, possibly by the fecal-oral route, or by the oral-oral route,
      e.g., kissing, vomitus. On occasion, transmission occurs from person to person
      via contaminated endoscopes. Other gastric Helicobacter-like organisms have now
      been observed in a variety of animals, including rodents, primates, swine, and
      ferrets, but, with the exception of primates and possibly cats, these isolates
      are clearly different from human isolates. Foodborne transmission would not be
      unusual.

PMID- 15156040
TI  - Microbiological test for sanitation of equipment in the food factory.
AB  - Microbiological sampling of utensils, tableware, and kitchen ware, in addition to
      equipment, permits objective evaluation of sanitation practices and procedures
      used for these items from food service operations.

PMID- 15156041
TI  - Spectrophotometric determination of histamine in fisheries using an enzyme
      immunoassay method.
AB  - The biogenic amines are low-weight organic bases that exhibit variable biological
      activity. Approximately 30 vasoactive and psycoactive amines have been found in
      foodstuffs. Histamine, tyramine, phenylethylamine, tryptamine, cadaverine,
      putrescine, spermine, and spermidine are examples of biogenic amines detectable
      in meat and its derivatives. These amines occur naturally in animals, plants, and
      microorganisms owing to their natural metabolic processes, and are usually formed
      by decarboxylation of amino acids.Histamine, 5-imidazol-ethylamine (MW 111), is
      produced by oxidative decarboxylation of histidine, and decarboxylase-positive
      microorganisms are able to produce it as a byproduct of their action on host
      tissues. This process, associated with enterobacteria such as Escherichia,
      Salmonella, Clostridium, and Bacillus, can be fast if the meat storage conditions
      are inadequate.Additionally, because of its nonvolatile behavior, histamine may
      bestow toxicity on the product even before it is considered decayed or
      organoleptically unacceptable. Secondary amines such as piperidine and
      pyrrolidine can be produced in the catabolism of histamine, and they, in turn,
      are precursors of nitrosamines, substances with known carcinogenic activity. Some
      cases of histamine toxicity have been reported.

PMID- 15156042
TI  - Flavonoids from Argentine Tagetes (Asteraceae) with antimicrobial activity.
AB  - The flavonoids, constituting one of the most numerous and widespread groups of
      natural plant constituents, are important to humans not only because they
      contribute to plant colors but also because many members are physiologically
      active. These low-molecular-weight substances, found in all vascular plants, are
      phenylbenzopyrones. Over 4000 structures have been identified in plant sources,
      and they are categorized into several groups. Primarily recognized as pigments
      responsible for the autumnal burst of hues and the many shades of yellow, orange,
      and red in flowers and food, the flavonoids are found in fruits, vegetables,
      nuts, seeds, stems, flowers, and leaves as well as tea and wine and are important
      constituents of the human diet. They are prominent components of citrus fruits
      and other food sources. Flavonols (quercetin, myricetin, and kaempferol) and
      flavones (apigenin and luteolin) are the most common phenolics in plant-based
      foods. Quercetin is also a predominant component of onions, apples, and berries.
      Such flavanones as naringin are typically present in citrus fruit, and flavanols,
      particularly catechin, are present as catechin gallate in such beverages as green
      or black tea and wine. Some major sources of flavonoids are outlined in Table 1.
      The daily intake of flavonoids in humans has been estimated to be approx 25 mg/d,
      a quantity that could provide pharmacologically significant concentrations in
      body fluids and tissues, assuming good absorption from the gastrointestinal
      tract. Biological activity of flavonoids was first suggested by Szent-Gyorgyi
      1938, who reported that citrus peel flavonoids were effective in preventing the
      capillary bleeding and fragility associated with scurvy. The broad spectrum of
      biological activity within the group and the multiplicity of actions displayed by
      a certain individual members make the flavonoids one of the most promising
      classes of biologically active compounds.

PMID- 15156043
TI  - Purification of bacteriocins produced by lactic acid bacteria.
AB  - Bacteriocins are antibacterial substances of a proteinaceous nature that are
      produced by different bacterial species. Lactic acid bacteria (LAB) produce
      biologically active peptides or protein complexes that display a bactericidal
      mode of action almost exclusively toward Gram-positive bacteria and particularly
      toward closely related species. Generally they are active against food spoilage
      and foodborne pathogenic microorganisms including Bacillus cereus, Clostridium
      perfringens, Staphylococcus aureus, and Listeria monocytogenes. There is an
      increased tendency to use natural occurring metabolites to prevent the growth of
      undesirable flora in foodstuffs. These metabolites could replace the use of
      chemical additives such as sorbic acid, sulfur dioxide, nitrite, nitrate, and
      others. For instance, bacteriocins produced by LAB may be promising for use as
      bio-preservaties. Bacteriocins of lactic acid bacteria are typically cationic,
      hydrophobic peptides and differ widely in many characteristics including
      molecular weight, presence of particular groups of amino acids, pI, net positive
      charge, and post-translational modifications of certain amino acids. This
      heterogeneity within the LAB bacteriocins may explain the different procedures
      for isolation and purification developed so far. The methods most frequently used
      for isolation, concentration, and purification involve salt precipitation of
      bacteriocins from culture supernatants, followed by various combinations of gel
      filtration, ion-exchange chromatography, and reverse-phase high-performance
      liquid chromatography (RP-HPLC). In this chapter, a protocol is described that
      combines several methods used in our laboratory for the purification of two
      cationic bacteriocins, Lactocin 705AL and Enterocin CRL10, produced by
      Lactobacillus casei CRL705 and Enterococcus mundtii CRL10, respectively.

PMID- 15156044
TI  - Production of antimicrobial substances by lactic acid bacteria I: determination
      of hydrogen peroxide.
AB  - Restoration of the balance of different ecological niches has been proposed as a
      way to control the income of pathogenic microorganisms. The genus Lactobacillus
      has been used in different human and animal tracts as probiotic microorganisms
      with this objective in mind. The characteristics of the strains proposed as
      probiotics have been published or patented under the process of elaboration of
      different types of products. One of the mechanisms suggested to control the
      vaginal ecosystem is the production of antagonistic substances (lactic acid,
      bacteriocins, or H2O2). The H2O2-producing microorganisms present in the vagina
      of healthy women have been suggested as some of the bacteria responsible for
      maintenance of ecological balance, mainly in pregnant women. The absence of these
      microorganisms is related to a higher risk of: bacterial vaginosis, recurrent
      urinary tract infections by Escherichia coli, and acquisition of human
      immunodeficiency virus type 1 (HIV-1). Bauer has proposed that H2O2-producing
      lactobacilli also might exert control over vaginal cancer through specific
      interactions of reactive oxygen species, such as superoxide anion, hydroxyl
      radicals, and hypochlorous acid. The conversion of H2O2 into more toxic compounds
      during the oxidative process is potentiated by peroxidase and halures. This
      enzyme and some halures, such as chloride and bromide, are present in vaginal
      washes in sufficient amounts to allow an optimal environment for successful
      inhibition of pathogens. In vitro tests provide an approach for determining the
      ability of lactobacilli to produce H2O2. The H2O2 amounts produced in such
      systems are probably not a direct reflection of what happens in the vaginal tract
      of women or animals, which is not yet know. However, there is a registered patent
      with an H2O2-generating L. crispatus strain, also supporting the use of H2O2
      producing lactobacilli to restore the vaginal ecosystem.

PMID- 15156045
TI  - Production of antimicrobial substances by lactic acid bacteria II: screening
      bacteriocin-producing strains with probiotic purposes and characterization of a
      Lactobacillus bacteriocin.
AB  - Bacteriocins have been defined as proteinaceous, bactericidal substances
      synthesized by bacteria, which usually have a narrow spectrum of activity, only
      inhibiting strains of the same or closely related species. The term bacteriocin
      like substance is applied to antagonistic substances that are not completely
      defined or do not fit the typical criteria of bacteriocins. They have been
      reported to inhibit a wide range of both Gram-positive and Gram-negative bacteria
      as well as fungi. Lactobacillus species are the dominant microorganisms isolated
      from the vagina of healthy premenopausal women. In this environment, they exert a
      protective effect against pathogenic microorganisms by different mechanisms such
      as production of antimicrobial agents, which include organic acids, hydrogen
      peroxide, and probably bacteriocins. The production of bacteriocins by vaginal
      lactobacilli has been demonstrated in vitro; however, it is not yet well
      established whether they are produced in vivo as another antagonistic mechanism
      exerted by the normal microflora.Bacteriocin-producing bacteria as well as
      bacteriocins per se are of growing interest as biological controls in the
      manufacture of beverages and fermented products, mainly in the area of dairy
      products. These bacteria have also been proposed as probiotic candidates for
      human or animal use. The objectives of the present chapter are to describe the
      methods employed for: 1. Detection of production of bacteriocins among vaginal
      Lactobacillus strains. 2. Characterization of the bacteriocin or bacteriocin-like
      substances. 3. Study of the kinetics of production and mode of action of
      bacteriocins. 4. Determination of the inhibition of pathogenic microorganisms by
      bacteriocin-producing strains in mixed cultures.

PMID- 15156046
TI  - Statistical models to optimize production of probiotic characteristics.
AB  - The use of probiotic microorganisms has been widely promoted in the last 20
      years. Probiotics have applied to the gastrointestinal tract as capsules or as
      fermented milks. The characteristics of the strains proposed as probiotics have
      been published or patented after elaboration of the product. The first step in
      designing a probiotic product is to isolate and characterize strains with
      beneficial properties. Our group has reported the isolation and characterization
      of 134 strains of lactobacilli from the vagina of women from our city. Surface
      properties and the production of antagonistic substances has also been published.
      From these studies, certain strains were selected because they shared probiotic
      characteristics. The second step in the design of a pharmaceutical product is to
      determine the optimal conditions for obtaining the highest amount of viable
      microorganisms, as well as the best conditions to produce antagonistic
      substances. To perform these types of experiments, laboratory assays can be
      carried out to determine the optimum conditions in which the microorganisms can
      be cultured. Growth parameters and optimal growth conditions can be studied by
      the classical methodology or by the application of alternative methodologies.
      Alternative methods have been widely used in the food industry, including
      experimental designs to test multiple conditions at the same time, complemented
      by the use of statistical models to evaluate and compare all the conditions
      tested. The object of this chapter is to describe the experimental designs used
      to study the technological characteristics of vaginal probiotic lactobacilli as
      well as the application of statistical models for evaluation of the different
      conditions tested for the production of biomass and antagonistic substances in
      these bacteria. With this objective in mind, in the present chapter, the
      following areas are explored: 1. Growth experiments performed to study the effect
      of temperature, pH, agitation, and culture media on the growth and production of
      antagonistic substances by vaginal lactobacilli. 2. Fractional and complete
      factorial experimental designs used to perform the growth experiments. 3.
      Statistical models applied to evaluate the growth parameters and their
      modifications under the conditions assayed.

PMID- 15156047
TI  - Meat-model system development for antibacterial activity determination.
AB  - Bacteriocins are antibacterial substances produced by many different bacterial
      species. Although the bacteriocins form a heterogenous group with respect to
      production of bacteria, antibacterial spectrum, mode of action, and chemical
      properties, they are by definition proteinaceous compounds that are bactericidal
      toward organisms taxonomically close to the producer. The ability of lactic acid
      bacteria (LAB) to compete and finally dominate in mixed fermentations has been
      attributed to the production of several antimicrobial metabolites such as organic
      acids, carbon dioxide, hydrogen peroxide, diacetyl, and bacteriocins. The
      antimicrobial activities of the LAB have long been known, but their bacteriocins
      have received limited attention until recently. Numerous strains of lactic acid
      bacteria associated with food systems are capable of producing bacteriocins, or
      antibacterial proteins with activity against foodborne pathogens and
      contaminants. Recently, considerable enphasis has been placed on the
      physicochemical, biochemical, and genetic characterization of these proteins.
      Many methods for the detection of bacteriocin production as well as the
      determination of the potency of bacteriocin preparations have been described. All
      the usual techniques are based on the fact that bacteriocins can diffuse in solid
      or semisolid culture media, which are subsequently inoculated with a suitable
      indicator strain. This method has long been shown to have a good perfomance in
      the characterization of new bacteriocins. Although results obtained from broth
      systems show that bacteriocins inhibit target organisms, applied studies must be
      performed to confirm their effectiveness in food. As many lactic acid bacteria
      associated with meat products were described to be important natural bacteriocin
      producers, it has been necessary to assay their inhibitory efficacy in meat or
      meat products. Because of the complexity of these kinds of foods a simplified
      meat-model system was developed to determine the inhibitory activity of a
      bacteriocin.

PMID- 15156048
TI  - Colonization capability of lactobacilli and pathogens in the respiratory tract of
      mice: microbiological, cytological, structural, and ultrastructural studies.
AB  - Respiratory tract infections are among the bacterial infections that affect
      humans with higher frequency. Those produced by Streptococcus pneumoniae are
      reported to have the highest incidence in the world, affecting both children and
      old people. As a 2001 report from the World Health Organization expressed it, the
      basic fight of children under 5 yr old is to survive. Five different conditions
      (acute respiratory infections, diarrhea, measles, palludism, and undernutrition)
      directly produce more than 50% of the deaths in this age group. Respiratory tract
      infections in the developing countries in the Americas are among the first three
      causes of death in children under 1 yr and between the first and second cause in
      children between 1 and 4 yr old. Pneumonia is responsible for 85 and 90% of
      deaths in children under 5 yr old (approx 150,000 annually), 95% of them
      occurring in the developing countries in the Americas. There is an increased
      worldwide tendency to use preventive measures and to consume products that help
      to maintain the health status of the individual. Thus the use of probiotics has
      increased systematically during the last decade, and the scientific literature
      trying to demonstrate the positive effect of such preparations has also
      increased. The term probiotic has been applied to products that (1) contain live
      microorganisms, freeze-dried or included in fermented products or (2) improve the
      health status of humans and animals, exerting effects in the mouth or
      gastrointestinal tract (included in foods or capsules), in the respiratory tract
      (as aerosols), or in the urogenital tract (by local application)Having in mind
      the high incidence of respiratory tract infections, and looking for preventive
      measures as well as the possible applications of probiotics, the aim of this
      chapter was to use mice as experimental models to determine whether members of
      the genus Lactobacillus were able to colonize and give protection from infections
      after inoculation by the intranasal route. To this end, the following procedures
      were carried out: 1. Screening of the predominant bacterial species in
      respiratory organs. 2. Study of the kinetics of colonization of the different
      groups of microorganisms from 15 d up to adult (2 mo). 3. Screening of the
      probiotic characteristics of all the isolated strains.

PMID- 15156050
TI  - Effect of lactobacilli administration in the vaginal tract of mice: evaluation of
      side effects and local immune response by local administration of selected
      strains.
AB  - Lactobacilli are the predominant microorganisms in the vaginal tract of human and
      some homeothermic animals. They can maintain the ecological equilibrium of the
      tract by protecting against pathogenic microorganisms. In the last few years,
      there has been an increased tendency to use probiotic microorganisms to restore
      the ecological equilibrium and to protect against infections. This principle has
      been widely applied to the gastrointestinal tract. More recently, some other
      studies have reported the application of probiotics in different tracts, for
      example, the urogenital or respiratory tract. One of the objectives of our group
      is to design probiotic products for the urogenital tract. With this purpose,
      lactobacilli were isolated from the human vagina, and later some of them were
      selected for their probiotic characteristics (production of antagonistic
      substances or adhesion capability). The application of probiotic products in the
      vaginal tract has been approached empirically; some pharmaceuticals containing
      these microorganisms are available in the United States or Europe or are
      protected under the patent process or intellectual property rights. There are not
      enough studies in humans or animals to determine whether their administration can
      produce some type of collateral or adverse effect. Using Balb/c mice as the
      experimental model, the object of the present work was to study (1) whether
      intravaginal administration of human lactobacilli can produce colonization of the
      tract; (2) whether such administration produces some type of adverse or
      collateral effect; and (3) whether probiotics are able to stimulate the local
      immune system. Keeping in mind that hormones can affect the colonization or
      persistence ability of microorganisms, and with the purpose of having all animals
      at the same point in the sexual cycle, animals were cycled with estradiol 48 h
      before inoculation with lactobacilli. They were then inoculated im with hormones
      48 h before beginning microorganism inoculations. Later they were intravaginally
      inoculated with the appropriate dose of each Lactobacillus strains. The animals
      were sacrificed on different days after inoculation to perform the following
      studies: 1. Microbiological assays: To determine the number of lactobacilli in
      the tract (in vaginal washes or in organ homogenates), by plating the samples in
      selective media containing antibiotic (to differentiate the resident flora from
      those administered experimentally).

PMID- 15156049
TI  - Effects of estrogen administration on the colonization capability of lactobacilli
      and Escherichia coli in the urinary tracts of mice.
AB  - The use of probiotic microorganisms has been widely promoted in the last 20 yr.
      They have been used in the gastrointestinal tract as capsules or as fermented
      milks. The characteristics of the strains proposed as probiotics have been
      published or patented under an elaboration process. The first step in designing a
      probiotic product is to isolate and characterize strains with some beneficial
      properties. The second step is to determine the optimal conditions to obtain the
      highest amount of viable microorganisms, together with the study of the best
      conditions to produce antagonistic substances. Urinary tract infections (UTIs)
      constitute a common cause of illness in pre- and postmenopausal women. It was
      estimated that 40-50% of adult women suffer a cystitis during their life. Ninety
      percent of acquired ambulatory UTIs and 30% of nosocomial infections are produced
      by Escherichia coli. The healthy human urinary tract is free of microorganisms,
      except for the anterior urethra, which is colonized by indigenous microbiota. The
      vaginal environment is a dynamic and complex ecological system with a highly
      heterogeneous microflora; thus favorable conditions exist for the colonization
      process, which is also affected by factors external to the tissues. The distal
      urethra and periurethral areas are separated ecological niches, both covered by
      the vaginal secretions that contain approx 109 microorganisms/mL. In these
      secretions, members of the genus Lactobacillus are predominant. Bacterial
      colonization does not increase because of the urinary flux, which clears the
      bacterial cells from the outer surfaces, as well as other factors such as pH,
      osmolarity, and urea concentration.

PMID- 15156051
TI  - Determination of bacterial adhesion to intestinal mucus.
AB  - The epithelial cells in the small intestine are covered by a relatively thick
      layer of mucus, secreted by specialized cells, which consists of mucin, many
      small associated proteins, glycoproteins, lipids, and glycolipids. The mucus
      contains receptors that recognize specific adhesion proteins. Adhesion or close
      association of bacteria to the epithelial cells may further contribute to
      competitive exclusion. In addition, bacterial adhesion to intestinal mucus and
      epithelia seems to be important for individual stability of microbial flora.
      Although the mucus layer covering the gastrointestinal tract has been recognized
      for many years, it has only recently been of interest in the study of the
      adhesion between mucus and bacteria. In this chapter, we describe a method for
      the study of colonization of the gastrointestinal mucus by bacteria and determine
      the possible effects on adhesion of pathogenic organisms.

PMID- 15156052
TI  - Animal model for in vivo evaluation of cholesterol reduction by lactic Acid
      bacteria.
AB  - For many years, it has been recognized that elevated serum cholesterol is a risk
      factor associated with atherosclerosis and coronary heart disease, the latter
      being a major cause of death in Western countries. Numerous drugs that lower
      cholesterol have been used to treat hypocholesterolemic individuals. However, the
      undesirable side effects of these compounds have caused concerns about their
      therapeutic use. Ingestion of probiotic (beneficial for health) lactic acid
      bacteria (LAB) would possibly be a more natural method to decrease serum
      cholesterol in humans, as has been was reported. Previous studies have
      demonstrated that Lactobacillus reuteri administered in low doses has a
      hypocholesterolemic effect both therapeutically and preventively. One of the key
      studies in the development of a probiotic is to determine the minimal effective
      dose of live microorganisms that might be ingested without producing adverse
      effects (i.e., translocation) in the host. In this chapter, we describe an animal
      model that allows us to evaluate reduction in hypercholesterolemia by LAB and,
      also to determine the minimal dose of the microorganism, a critical step in the
      development of a safe probiotic product.

PMID- 15156053
TI  - Assessing survival of dairy propionibacteria in gastrointestinal conditions and
      adherence to intestinal epithelia.
AB  - The genus Propionibacterium consists of two principal groups, cutaneous and
      classical or dairy. Cutaneous species are predominant members of the microbial
      population of human skin and have also been isolated from the feces of humans and
      other vertebrate animals. They are often considered opportunistic organisms and
      have been occasionally associated with infections in humans. Dairy
      propionibacteria are microorganisms extensively used in the industry for
      manufacture of Swiss-type cheeses and biological production of propionic acid and
      vitamin B12. They can be isolated from soil, vegetables, silage, raw milk, and
      dairy products such as kefir and different cheeses with "eyes."In the last
      decade, several studies have demonstrated probiotic properties for members of the
      genus Propionibacterium. The effects claimed are based on the production of
      bacteriocins, vitamins, stimulation of growth of other colonic bacteria like
      bifidobacteria, beneficial modification of the composition and metabolic
      activities of the intestinal microflora, immunomodulation, and antimutagenic
      activity. It is thought that to produce many of these health benefits, the
      probiotic microorganisms must be able to survive the transit through the hostile
      conditions of the gastrointestinal tract (GIT) and remain at high levels in the
      intestine, avoiding removal by peristaltic contractions of the gut. In this
      sense, microorganisms with a short generation time or the ability to adhere to
      the intestinal mucosa will survive for prolonged periods in the body of the host.
      Therefore, two desirable properties for probiotic microorganisms are (1)
      resistance to gastric acidity, bile, and pancreatic enzymes; and (2) adhesion
      ability to mucosal surfaces. Dairy bacteria are traditionally not considered to
      persist as normal inhabitants of the human intestinal tract. Therefore, survival
      under GIT conditions and adherence are important properties to be considered, and
      tests to study them would be useful tools. In the present chapter we describe the
      methods used in our laboratory to assess survival, metabolic activity, and
      adhesion of dairy propionibacteria to intestinal epithelial cells after
      gastrointestinal digestion.

PMID- 15156054
TI  - Bacterial surface characteristics applied to selection of probiotic
      microorganisms.
AB  - For the study of probiotic microorganisms, the in vitro selection tests need to
      be based on a solid scientific foundation. Surface characteristics, one of the in
      vitro properties are used to evaluate the potentially probiotic strains of
      lactobacilli. Bacterial surface properties have been associated with attachment
      to a variety of substrata. Bacterial adhesion to tissues is considered the first
      step, and such adhesion can also determine the colonization capability of a
      microorganism. Through adhesion ability and colonization of tissues, probiotic
      microorganisms can prevent pathogen access by steric interactions or specific
      blockage on cell receptors. One of the main characteristics studied is the
      hydrophobic nature of the bacterial cell surface. To test this property,
      Rosenberg and Doyle divided microbial cell hydrophobicity assays into two
      categories. The first includes contact angle measurements (CAMs), partitioning of
      cells into one or another liquid phase (TTP), and adsorption of individual
      hydrophobic molecular probes at the cell surface. The second category includes
      microbial adhesion to hydrocarbons (MATH), hydrophobic interaction chromatography
      (HIC), and adhesion to polystyrene and other hydrophobic solid surfaces. The
      tests included in the first category measure hydrophobic properties of the outer
      cell surface as a whole; those in the second measure hydrophobicity in terms of
      adhesion. Finally, those bacterium classified as hydrophobic can be considered as
      able to mediate adhesion. The objective of this chapter is to describe three
      different methods applied in our laboratory for the study of bacterial surface
      properties. They can be used to screen characteristics of lactobacillus strains
      for probiotic purposes. They are: Microbial adhesion to hydrocarbons (MATH); Salt
      aggregation test (SAT); Hemagglutination (HA) reaction.

PMID- 15156055
TI  - Adhesion ability of Lactobacillus to vaginal epithelial cells: study by
      microbiological methods.
AB  - Adhesion of lactobacilli to the epithelium has been described as the first step
      in the formation of a barrier to prevent undesirable microbial colonization;
      consequently, it has been defined as a characteristic of interest for selecting
      probiotic strains. Several methods have been described to predict the adhesion
      ability of Lactobacillus. Early studies were phenomenological: it was useful to
      determine whether a particular bacterium could hemagglutinate, or bind to coated
      particles. Later, studies based on the adhesion of bacteria to epithelial cells
      in vitro were developed. These last assays were based on the numbers of bacteria
      attached to epithelial cells, which were determined by counting stained
      microorganisms under light microscopy or by measuring the radioactivity of
      previously radiolabeled bacteria. Because the microscope technique, had some
      disadvantages, a modification was developed in our laboratory. The technique
      described in this chapter is a modification of the Mardh and Westron method. The
      method allows the study of the adhesion ability of bacteria, even if they are
      aggregating or if they are high-adherent bacteria covering a large area of the
      epithelial cell surface. Determination of the number of adherent bacteria by
      counting colonies grown in a selective media avoids the time-consuming, tedious,
      and hazardous counting under the light microscope and the use of radioactive
      methods.

PMID- 15156056
TI  - Hydroxylapatite beads as an experimental model to study the adhesion of lactic
      acid bacteria from the oral cavity to hard tissues.
AB  - The oral environment contains many different types of microorganisms, including
      both Gram-negative and Gram-positive cocci, bacilli, and spirochetes. From the
      ecological point of view, the oral cavity is a perfect niche for certain bacteria
      such as lactobacilli because they interact, forming different types of
      communities. Lactobacilli have been associated with the generation of caries in
      some reports, secondary to the cariogenic Streptococcus. In previous papers, the
      isolation and identification of 145 strains from healthy subjects and from
      subjects with active caries were performed. Strains were characterized by their
      surface properties and also by the production of inhibitory substances. From all
      the strains, one isolated from the teeth of healthy patients and another from a
      patient with caries, sharing some surface properties, were selected for further
      study of their adhesion properties in an experimental model by using
      hydroxylapatite beads. Adhesion is the first step in the association of
      microorganisms with surfaces or mucous membranes. The first approach is a
      nonspecific interaction of both surfaces; later some other types of interactions
      can occur, involving more specific mediators of adhesions. Many different assays
      are available to study the adhesion phenomenon; some of them use predictive
      characteristics, and others use experimental models resembling the in vivo
      situation. Two model systems predominate. The most widely used has been saliva
      coated hydroxylapatite or hydroxylapatite coated with buffers, proteins, and
      other substances. In an attempt to increase knowledge of the mechanisms of
      adhesion of oral lactobacilli with hard surfaces, this chapter describes an
      experimental model for studing the adhesion between lactobacilli and hard tissues
      represented by hydroxylapatite, the component most abundant in the teeth. The
      following steps were performed: 1. Obtaining the microorganisms. 2. Preparation
      of the hydroxylapatite beads. 3. Adhesion assay.

PMID- 15156057
TI  - Microtechnique for identification of lactic acid bacteria.
AB  - Certain gut species are pathogens, but a number of other resident bacteria may be
      of some benefit to host health. Examples include enterococci, lactobacilli,
      propionibacteria, and bifidobacteria, which are present in the colon in
      significant numbers. Identification and classification are not identical. A group
      can be identified only after it has been classified, based on a pattern of
      properties shown by all the members of the group that other groups do not
      possess. The properties used in identification are often different from those
      used in classification. Biochemical, nutritional, and physiological
      characterization tests (usually carried out in bottles and tubes of solid and
      liquid media and on plates) have been developed and modified since the earliest
      days of bacteriology. Generally, the characteristics chosen for an identification
      plan should be easily determinable, whereas those used for classification (such
      as DNA homology) may be quite difficult to determine. Genera and species
      identification might not be based on only a few tests, but rather on the pattern
      given by a whole battery of tests. The members of the family Lactobacillaceae
      represent one example of this. Some probiotic strains can be selected for their
      benefical properties as active antimicrobial agents against pathogenic
      microorganisms, hydrophobic ability, presence of substances with a capacity for
      adherence to epithelium, and so on. After isolation, identification is an
      important step before selecting probiotic strains. These identifications can be
      facilitated through microtechniques. To alleviate the need to inoculate large
      numbers of tubes with media (conventional test), some rapid multitest systems
      have been devised and are commercially available (such as the API or Biolog
      systems). Although they are expensive for large studies and not always
      sufficiently versatile, these kits do offer the advantages of convenience,
      miniaturization, rapidity, and, above all, strict standardization. Other methods
      such as ribotyping or randomly amplified polymorphic DNA do not take into account
      the phenotypic characteristics (biotyping). In this chapter, we describe a
      simple, rapid, and economical microplates technique to identify lactic acid
      bacteria and enterobacteria based on general metabolic characteristics, adapted
      for routine study of a large number of strains.

PMID- 15156058
TI  - Differentiation of lactic acid bacteria strains by postelectrophoretic detection
      of esterases.
AB  - Lactic acid bacteria (LAB) comprise a diverse group of Gram-positive, non-spore
      forming microorganisms. These bacteria are widely used in food technology. The
      species identification of LAB depends mainly on physiological and biochemical
      criteria. The esterolytic systems of LAB remain poorly characterized. Esterases
      (EC 3.1.1.3) represent a diverse group of hydrolases catalyzing the cleavage and
      formation of esters bonds Screening of esterases is usually performed either by
      employing chromophoric substances (e.g., alpha- or beta-naphthyl esters of short
      chain fatty acids). The post-electrophoretic detection of esterases is a
      sensitive technique applied in bacterial systems, that mainly provides
      information on the similarity of strains within the same species or subspecies
      according to their esterase patterns. This technique is principally used to
      determine the number and substrate specificity of esterases and lipases,
      revealing the complexity of lipase and esterase systems. The present chapter
      describes the technique of polyacrylamide gel electrophoresis (PAGE; in the
      absence of sodium dodecyl sulfate [SDS]), in non-denaturing conditions, to find
      intracellular fractions for strain typing of LAB.

PMID- 15156059
TI  - Determination of esterolytic and lipolytic activities of lactic acid bacteria.
AB  - Lactic acid bacteria (LAB) are considered weakly lipolytic compared with many
      other groups of bacteria (e.g., Pseudomonas, Bacillus, and Achromobacter). The
      esterolytic and lipolytic systems of dairy LAB remain poorly characterized.
      Esterases from lactic acid bacteria, yeasts, and Pseudomonas organisms may be
      involved in the development of fruity flavors in foods, and pregastric lipase and
      esterases are essential for the development of typical flavor in Italian cheese.
      Microbial lipases and esterases may improve quality or accelerate the maturation
      of cheeses, cured bacon, and fermented sausages. Lipases are defined as glycerol
      ester hydrolases (EC 3.1.1.3) that hydrolyze tri-, di-, and monoglycerides
      present at an oil-water interface. Esterases (EC 3.1.1.6) hydrolyze esters in
      solution and may also hydrolyze tri- and especially di- and monoglycerides
      containing short-chain fatty acids. Some probiotic strains of LAB can hydrolyze
      the triglycerides, releasing most short and medium chain, and essential fatty
      acids, which are valuable to today's health-conscious consumer. Medium chain
      fatty acids (C6-C14), in particular, have become accepted treatment for patients
      with malabsorption symptoms, a variety of metabolic disorders, cholesterol
      problems, and infant malnutrition. These probiotic bacteria could alleviate
      lipase deficiency in the digestive tract during digestion (steatorrhea). In this
      chapter, we describe different methods routinely used in our laboratory to
      determine the esterolytic and lipolytic activity of LAB. These techniques include
      the use of alpha- and beta-naphthyl derivatives of fatty acids (chromogenic
      method), the p-nitrophenyl (pNP) derivative of fatty acids (chromogenic method),
      and triglycerides (agar-well assay technique and titrimetric test) as substrates.

PMID- 15156060
TI  - Meat-model system development for proteolytic activity determination.
AB  - Many technological parameters that affect the nature and functional properties of
      proteins are involved in the preparation of meat products. The dry-curing process
      is quite complex because of the coexistence of enzymes from endogenous and
      bacterial origins. The protein breakdown that takes place during the ripening of
      dry fermented sausages leads to an increase in the concentration of peptides and
      free amino acids. The proteolytic events have been thoroughly investigated not
      only because of their physiological significance but also for their technological
      connotations in terms of texture and flavor development. Lactic acid bacteria and
      Staphylococcus or Kocuria are used as starter cultures in fermented meat
      products. In recent years, the proteolytic system of lactobacilli involved in
      meat fermentation became the focus of an increasing number of studies because of
      the technological roles of these organisms. Although results obtained from broth
      systems show proteolytic activity, studies involving food systems must be done to
      confirm their effectiveness. A simplified soluble muscle extract to determine the
      capacity to degrade meat proteins by lactic acid bacteria was developed using a
      spectrophotometric method based on the reaction of the alpha-amino groups
      released by hydrolysis with o-phtaldialdehyde and beta-mercaptoethanol to form an
      adduct (1-thioalkyl-2-alkylisoindoles) that is enhanced at basic pH and absorbs
      strongly at 360 nm.

PMID- 15156061
TI  - beta-Glucuronidase method to determine mastitis levels in goat milk.
AB  - Mastitis is a general term that refers to the inflammation of the mammary gland.
      It is the most common illness in dairy farms and it has different causes, mainly
      a great number of germs that infect the gland. These infectious diseases induce
      gross variations in milk composition, reflected by physical, chemical, and
      bacteriological changes. They produce milk jellification, a decrease in important
      components such as lactose, casein, and fats and minerals such as calcium,
      phosphorus, and potassium and increases in other unimportant technological
      components, such as serum proteins and chlorides; all these affect the cheese
      efficiency and the starter culture action. Assuming that cheese making is the
      principal use of goat milk in industry, an evaluation of the quality of the milk
      used as the raw material is of fundamental importance. It is impossible to obtain
      quality products by using milk with an anomalous chemical composition. Somatic
      cell count (SCC) is the indicator most used for mastitis detection. These cells,
      which are contained in milk, can be grouped into three types: epithelial cells,
      blood cells, and cytoplasmatic particles. During an attack of mastitis, the
      immune defenses of the udder are activated, polynucleated leukocytes pass from
      the blood toward the mammary gland in large numbers, and the number of somatic
      cells in the milk increases. The level of somatic cells in goat milk is
      characterized by great variability between different countries and between
      regions of the same country. Different authors show averages between 750,000 and
      5,400,000 cells/mL. These values differ greatly between cow and goat milk, mainly
      because normally nonleukocytic cell-like particles can be found as a result of
      the particular apocrine secretion process in the goat mammary gland. These
      particles are large fragments of cytoplasm originating from the distal portion of
      alveolar secretory cells and are of similar size (5-30 microm in diameter) to
      milk leukocytes. They contain abundant RNA-positive granular material (associated
      with dilated cisternae of the rough endoplasmic reticulum), large amounts of
      protein, and some lipids, but no DNA. Thus it is important to use techniques that
      disregard these other substances and allow only a count of somatic cells.

PMID- 15156062
TI  - Differences between biogenic amine detection by HPLC methods using OPA and dansyl
      derivates.
AB  - Biogenic amines can be formed and degraded as a result of normal metabolic
      activity in animals, plants, and microorganisms and are usually produced by the
      decarboxylation of amino acids. Recent trends in food security are promoting an
      increasing search for trace compounds that can affect human health. Although they
      are present in fermented foods and beverages in low quantities, they exhibit
      interactions with normal human metabolism (e.g., having vasoactive or
      psychoactive properties) that justify the research on their presence in foods and
      the possible related toxicological effects that they may cause. Estimation of the
      biogenic amines histamine, tyramine, agmatine, putrescine, and cadaverine is
      important not only from the point of view of their toxicity, but also because
      they can be used as indicators of the degree of freshness or spoilage of food.
      Until recently, because of the difficulty in detecting and quantifying amines
      reliably we have had insufficient information about their occurrence in different
      types of foods and beverages. These problems are related to matrix interference
      (e.g., the presence of free amino acids) and the low levels at which the amines
      are found. Early techniques for the determination of biogenic amines in foods
      were based on thin-layer chromatography. More modern analytical techniques have
      since been developed that allow the acquisition of reliable quantitative data and
      better separation/resolution of various amines. The quantitative determination of
      biogenic amines is generally accomplished by overpressure-layer chromatography,
      high-performance liquid chromatography (HPLC), and gas chromatography. The use of
      reverse-phase column and precolumn derivatization was more efficient and faster
      than the conventional ion-exchange techniques. This study was conducted to
      evaluate two HPLC derivatization methods for quantitative determination of
      biogenic amines: the method described by Gonzales de Llano et al. for amino acid
      analysis and the method described by Eerola et al.

PMID- 15156063
TI  - Microflora of the gastrointestinal tract: a review.
AB  - The mucosal surface of the human gastrointestinal (GI) tract is about 200-300 m2
      and is colonized by 1013-14 bacteria of 400 different species and subspecies.
      Savage has defined and categorized the gastrointestinal microflora into two
      types, autochthonous flora (indigenous flora) and allochthonous flora (transient
      flora). Autochthonous microorganisms colonize particular habitats, i.e., physical
      spaces in the GI tract, whereas allochthonous microorganisms cannot colonize
      particular habitats except under abnormal conditions. Most pathogens are
      allochthonous microorganisms; nevertheless, some pathogens can be autochthonous
      to the ecosystem and normally live in harmony with the host, except when the
      system is disturbed. The prevalence of bacteria in different parts of the GI
      tract appears to be dependent on several factors, such as pH, peristalsis, redox
      potential, bacterial adhesion, bacterial cooperation, mucin secretion, nutrient
      availability, diet, and bacterial antagonism. Because of the low pH of the
      stomach and the relatively swift peristalsis through the stomach and the small
      bowel, the stomach and the upper two-thirds of the small intestine (duodenum and
      jejunum) contain only low numbers of microorganisms, which range from 103 to 104
      bacteria/mL of the gastric or intestinal contents, mainly acid-tolerant
      lactobacilli and streptococci. In the distal small intestine (ileum), the
      microflora begin to resemble those of the colon, with around 107-108 bacteria/mL
      of the intestinal contents. With decreased peristalsis, acidity, and lower
      oxidation-reduction potentials, the ileum maintains a more diverse microflora and
      a higher bacterial population. Probably because of slow intestinal motility and
      very low oxidation-reduction potentials, the colon is the primary site of
      microbial colonization in humans. The colon harbors tremendous numbers and
      species of bacteria. However, 99.9% of colonic microflora are obligate anaerobes.

PMID- 15156064
TI  - Public health implications related to spread of pathogens in manure from
      livestock and poultry operations.
AB  - During the 20th century, food animal agriculture grew from small operations,
      where livestock (cattle, sheep, and swine) and poultry (chickens and turkeys) had
      access to free range, to large operations where animals and poultry were
      concentrated and confined to feed lots or buildings. The quantity of manure
      produced by confinement animals in the United States has been estimated to be in
      excess of 61 million tons of dry matter per year, and another report states that
      1.2 billion tons of manure are produced by cattle annually in the United States
      (US Senate Agricultural Committee, 1998). As urban developments have come closer
      to livestock operations, there has been increasing public concern for the impact
      of the latter on public health and the environment. Although management practices
      for livestock production have increased in efficiency, insufficient attention has
      been given to managing and utilizing wastes so that they benefit rather than
      pollute the environment. Animal manure includes urine and various bodily
      secretions such as those from the nose, vagina, and mammary glands. Dust from
      animals and manure may be blown from buildings by powerful fans, and manure is
      often piled near the animal quarters or is spread on land in solid or liquid
      form. Public concerns associated with disposal of animal manure include
      objectionable odors, flies, excessive levels of phosphorous and nitrogen, and the
      potential for spread of human pathogens. It has been observed that despite
      linkages between outbreaks of gastroenteritis in humans and livestock operations,
      the importance of animal manure in the spread of infectious agents tends to be
      underestimated.

PMID- 15156065
TI  - Molecular aspects of disease pathogenesis in the transmissible spongiform
      encephalopathies.
AB  - The transmissible spongiform encephalopathy (TSE) diseases are a group of rare,
      fatal, and transmissible neurodegenerative diseases that include kuru and
      Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, transmissible mink
      encephalopathy (TME), and chronic wasting disease (CWD) in mule deer and elk.
      Over the last 20 yr, they have gone from a fascinating but relatively obscure
      group of diseases to one that is a major agricultural and economic problem as
      well as a threat to human health. The shift in the relative impact of the TSE
      diseases began in the late 1970s when the United Kingdom altered the process by
      which animal carcasses were rendered to provide a protein supplement (i.e., meat
      and bone meal) to sheep, cattle, and other livestock. Several years later a new
      disease was recognized in the British cattle population. The pathological and
      immunohistochemical characteristics of the disease clearly placed it among the
      TSEs. The new disease was named bovine spongiform encephalopathy (BSE) by the
      scientific community and "mad cow disease" by the less-than-scientific press. At
      its peak in the UK, several thousand cattle a year were diagnosed with BSE, and
      millions of cattle were slaughtered. Introduction of the specified offals ban as
      well as banning the practice of feeding ruminants to other ruminants has led to a
      drastic decrease in the number of yearly BSE cases in the UK (less than 500 in
      2003), and the epidemic is clearly on the wane. However, BSE has now spread
      throughout the rest of Europe, as well as to Japan, Russia, Canada, and Israel
      and thus remains a worldwide problem.A primary concern following the
      identification of BSE in 1985 was that it might cross species barriers to infect
      humans. Initially, it was thought that transmission of BSE to humans was
      unlikely, given that humans appeared to be resistant to scrapie, an animal TSE
      that had been endemic in British sheep for centuries. However, a few years after
      BSE was first recognized, a previously unknown form of CJD (variant CJD or vCJD)
      was identified in young people in Great Britain. The hypothesis that vCJD was the
      consequence of exposure of humans to BSE has now been supported by several
      different studies, and over 140 cases of vCJD have been confirmed.

PMID- 15156066
TI  - Pharmacological utility of melatonin in reducing oxidative cellular and molecular
      damage.
AB  - This review briefly summarizes the actions of melatonin in reducing molecular
      damage caused by free radicals and associated oxygen- and nitrogen-based
      reactants. All the mechanisms by which melatonin is protective of such a wide
      variety of molecules, i.e. lipids, proteins, DNA, etc., and in such widely
      diverse areas of the cell and different organs are likely not yet all identified.
      Melatonin actions that have been identified include its ability to directly
      neutralize a number of toxic reactants and stimulate antioxidative enzymes.
      Furthermore, several metabolites that are formed when melatonin neutralizes
      damaging reactants are themselves scavengers suggesting that there is a cascade
      of reactions that greatly increase the efficacy of melatonin in styming oxidative
      mutilation. Suggested, but less well defined, processes which may contribute to
      melatonin's ability to reduce oxidative stress include stimulation of glutathione
      synthesis (an important antioxidant which is at high concentrations within
      cells), reducing electron leakage from the mitochondrial electron transport chain
      (which would reduce free radical generation), limiting cytokine production and
      inflammatory processes (actions that would also lower toxic reactant generation),
      and synergistic effects with other classical antioxidants (e.g. vitamins C, E and
      glutathione). Clearly which of these multiple mechanisms contribute to
      melatonin's high efficacy in curtailing oxidative damage remains to be clarified.
      Likewise, it is possible that the key action of melatonin in reducing molecular
      damage induced by oxygen and nitrogen-based metabolites remains to be identified.
      Finally, the review summarizes some of the large amount of data documenting the
      ability of melatonin to limit molecular and organ damage in two situations, i.e.
      ischemia-reperfusion and ionizing radiation, where free radicals are generally
      conceded as being responsible for much of the resulting tissue destruction.

PMID- 15156067
TI  - Genetic basis of neurodegeneration in familial Alzheimer's disease.
AB  - Alzheimer's disease (AD), the most common form of dementia, is characterized by
      two types of brain lesions, referred to as senile plaques and neurofibrillary
      tangles. Moreover, neuronal cell loss and synaptic degeneration appear in
      affected regions of the brain. A series of endoproteolytic cleavages of the
      amyloid precursor protein (APP) controlled by alpha, beta, and gamma-secretases
      leads to a formation of non-amyloidogenic (the alpha-secretase pathway) and
      amyloidogenic (the beta-secretase pathway) products which are essential for
      neurodegeneration. According to the "amyloid cascade hypothesis", the
      accumulation of amyloid beta (Abeta) peptides in the brain is a primary event in
      the pathogenesis of AD. One of the strong pieces of evidence supporting this
      hypothesis was the identification of pathogenic mutations within APP, presenilin
      1 and presenilin 2 genes responsible for familial autosomal dominant AD. These
      mutations affect APP processing causing overproduction of Abeta42. Finding
      specific inhibitors of the Abeta42 generation is a major goal of AD drug
      development programs now and the key challenge for the treatment of the most
      devasting disease of human brain.

PMID- 15156068
TI  - Synergistic effect of imipramine and amantadine in the forced swimming test in
      rats. Behavioral and pharmacokinetic studies.
AB  - Our previous studies demonstrated that joint administration of a tricyclic
      antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA
      receptor, amantadine (AMA), produced stronger "antidepressant" effect in the
      forced swimming test (Porsolt's test) than the treatment with either of drugs
      given alone. Since it has been suggested that, in addition to their other
      functions, dopamine and alpha(1)-adrenergic receptors may play a role in
      behavioral response in the forced swimming test, in the present study we examined
      the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin
      (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in
      combination with IMI in the forced swimming test in rats. We also measured the
      level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h
      after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA
      (20 mg/kg) produced stronger antidepressant-like effect than either of agents
      given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the
      forced swimming test) inhibited an antidepressant-like effect induced by co
      administration of IMI and AMA. The active behaviors in that test did not reflect
      an increase in general activity, since combined administration of IMI and AMA
      failed to enhance the locomotor activity of rats, measured in the open field
      test. Also sulpiride and prazosin did not decrease the exploratory activity
      induced by co-administration of IMI and AMA. The above result suggests that the
      dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism
      of synergistic action of IMI and AMA in the forced swimming test in rats. The
      pharmacokinetic interaction can be excluded, since AMA did not change
      significantly the antidepressant level in the rat plasma and brain, measured 1 h
      after exposure to the forced swimming test.

PMID- 15156069
TI  - Riluzole enhances the anti-seizure action of conventional antiepileptic drugs
      against pentetrazole-induced convulsions in mice.
AB  - Riluzole, a pre- and postsynaptic modulator of glutamate transmission,
      administered alone at doses of 5 and 10 mg/kg did not affect pentetrazole-evoked
      seizures in mice. However, it enhanced the anti-seizure action of valproate,
      phenobarbital, ethosuximide, although not that of clonazepam, in this model of
      experimental epilepsy. Keeping in mind that riluzole did not change plasma levels
      of antiepileptic drugs, a pharmacokinetic interaction, at least in terms of free
      plasma levels, does not seem probable. Regarding undesired effects, riluzole (5
      mg/kg) and its combination with valproate did not produce any motor or long-term
      memory impairment. In contrast, the concomitant treatment of riluzole (5 mg/kg)
      with valproate (144 mg/kg), phenobarbital (4.9 mg/kg), or ethosuximide (90
      mg/kg), resulted in a moderate motor deficit, but not long-term memory impairment
      in the tested mice. In conclusion, the results of the present study suggest that
      riluzole might occur effective as an additive drug in the treatment of myoclonic
      or absence epilepsy in humans.

PMID- 15156071
TI  - Receptors for vasoactive intestinal peptide and pituitary adenylate cyclase
      activating polypeptide in the goose cerebral cortex.
AB  - Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) in the goose cerebral cortex were characterized
      using two approaches: (1) in vitro radioreceptor binding of [(125)I]-VIP, and (2)
      effects of peptides from the VIP/PACAP/secretin family on cyclic AMP formation.
      The binding of [(125)I]-VIP to goose cortical membranes was rapid, stable, and
      reversible. Saturation analysis resulted in a linear Scatchard plot, suggesting
      binding to a single class of receptor binding sites with a high affinity
      (K(d)=0.76 +/- 0.13 nM) and high capacity (B(max)=70 +/- 7 fmol/mg of protein).
      Various peptides displaced the specific binding of 0.12 nM [(125)I]-VIP to the
      goose cerebral cortical membranes in a concentration-dependent manner. The
      relative rank order of potency of the tested peptides to inhibit [(125)I]-VIP
      binding to the goose cerebrum was: PACAP(38) asymptotically equal to mammalian
      VIP > or = PACAP(27) asymptotically equal to chicken VIP >>> PHI (peptide
      histidine-isoleucine) >> secretin (inactive). About 52% of specific [(125)I]-VIP
      binding sites in the goose cerebral cortex was sensitive to 5'
      guanylimidodiphosphate [Gpp(NH)p], a nonhydrolyzable analogue of GTP. PACAP(38)
      and PACAP(27) potently stimulated cyclic AMP formation in the goose cerebral
      cortical slices in a concentration-dependent manner, displaying EC(50) values of
      45.5 nM and 51.5 nM, respectively. Chicken VIP was markedly less potent than both
      forms of PACAP, mammalian VIP only weakly affected the nucleotide production,
      while effects evoked by PHI were negligible. It is concluded that the cerebral
      cortex of goose contains VPAC type receptors that are labeled with [(125)I]-VIP
      and are positively linked to cyclic AMP formation. In addition, the observed
      stronger action of PACAP, when compared to VIP, on cyclic AMP production in this
      tissue suggests its interaction with both PAC(1) and VPAC receptors.

PMID- 15156072
TI  - Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin
      induced hypertension.
AB  - Hyperleptinemia may be involved in the pathogenesis of obesity-associated
      hypertension, however, the mechanism of hypertensive effect of leptin has not
      been elucidated. We investigated the effect of experimental hyperleptinemia on
      renal function, renal Na(+), K(+)-ATPase and ouabain-sensitive H(+), K(+)-ATPase
      activities in the rat. Leptin administered for 7 days (0.25 mg/kg twice daily sc)
      decreased food intake on 6th and 7th day of treatment but had no effect on body
      weight. Systolic blood pressure was 30.5% higher in leptin-treated animals.
      Urinary excretion of sodium decreased by 35.0% following leptin treatment. Leptin
      had no effect on potassium and phosphate excretion as well as on creatinine
      clearance. The activity of Na(+), K(+)-ATPase in the renal cortex and medulla was
      higher in leptin-treated rats by 32.4% and 84.2%, respectively. In contrast,
      leptin had no effect on either cortical or medullary ouabain-sensitive H(+), K(+)
      ATPase. In pair-fed group, in which food intake was reduced to the level observed
      in leptin-treated group, no changes in sodium metabolism and renal Na(+), K(+)
      ATPase were observed. Leptin decreased urinary excretion of nitric oxide
      metabolites by 55.0% and urinary excretion of cGMP by 26.3%. Plasma concentration
      of atrial natriuretic peptide tended to be higher and urinary excretion of
      urodilatin was 64.9% higher in leptin-treated animals. These data suggest that
      hyperleptinemia decreases natriuresis by up-regulating Na(+), K(+)-ATPase and
      stimulating tubular sodium reabsorption. This effect is mediated, at least in
      part, by deficiency of nitric oxide (NO). Abnormal renal sodium retention and
      vasoconstriction associated with NO deficiency may contribute to leptin-induced
      hypertension and to blood pressure elevation in hypertensive obese individuals.

PMID- 15156070
TI  - A multicenter, placebo-controlled, double-blind study of efficacy of a new form
      of carbamazepine (Carbatrol) in refractory epileptic patients.
AB  - Carbatrol (CBR) is a new multiple-unit, sustained-release dosage form of
      carbamazepine (CBZ) developed by Pharmavene. We present a multicenter,
      outpatient, randomized, double-blind parallel group study (No PI 101) carried out
      in two centers in Poland. CBR was evaluated in 47 patients with uncontrolled
      partial onset seizures. During the 28-day baseline period, patients were required
      to have at least two seizures and to take CBZ at a therapeutic level, a second
      antiepileptic drug was allowed but not valproic acid (VPA ). Patients were
      randomized to VPA or to CBR (dosages 800, 1200, 1600 mg/day). Criteria for escape
      relative to baseline were: two-fold increase in monthly seizure frequency, two
      fold increase in 2-day seizure frequency, two-fold increase in weekly seizure
      frequency, single generalized tonic-clonic seizure (GTCs) if none occurred during
      baseline or prolongation of GTCs. The primary efficacy variable was the number of
      patients escaping in each treatment group. Nineteen patients on VPAand 7 on CBR
      met escape criteria. CBR adverse experiences were all mild or moderate in
      severity. CBR therapy was effective in the treatment of partial complex seizures
      with or without generalization.

PMID- 15156073
TI  - Central role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis
      promoted by leptin and insulin in perfused rat liver.
AB  - Leptin showed less prominent inhibiting effect on the activation of hepatic
      glycogen breakdown and gluconeogenesis promoted by cAMP. The role of cAMP in the
      inhibition of glycogen breakdown and gluconeogenesis induced by physiological
      levels of leptin (10 ng/ml) and insulin (20 microU/ml) in the perfused liver was
      investigated. Insulin but not leptin inhibited (p < 0.05) the activation of
      glycogen breakdown promoted by cAMP (3 microM). Contrary to cAMP, the activation
      of glycogen catabolism promoted by 8-Br-cAMP (0.3 microM), a cAMP analogue more
      resistant to hydrolysis by phosphodiesterase 3B (PD3B), was inhibited (p < 0.05)
      not only by insulin (20 microU/ml) but also by leptin (10 ng/ml). The effect of
      leptin, however, was less intense than that of insulin. To verify the
      participation of the intracellular levels of cAMP, the experiments were repeated
      with N(6)-monobutyryl-cAMP (N(6)-MB-cAMP), a cAMP analogue, which is not
      metabolized by PD3B. The activation of glycogen breakdown promoted by N(6)-MB
      cAMP (0.3 microM) was not affected by leptin or insulin. In agreement with the
      results regarding glycogen catabolism, insulin and leptin at 50 ng/ml but not
      leptin at 10 ng/ml inhibited (p < 0.05) the activation of gluconeogenesis
      promoted by cAMP (7.5 microM). Taken together, these results led us to postulate
      that the convergent signaling pathways of these two hormones causing the
      inhibition of glycogen catabolism and gluconeogenesis involve a reduction of
      intracellular cAMP. Thus, cAMP levels may play an important role in the cross
      talk between both hormones and for the insulin-like effects of leptin.

PMID- 15156074
TI  - Role of an aminothiazole derivative on ethanol- and thermally oxidized sunflower
      oil-induced toxicity.
AB  - It is a known fact that ethanol increases lipid levels in humans and experimental
      animals. In this study, we have investigated the effect of dendrodoine analogue
      (DA), DA-[4-amino-5-benzoyl-2-(4-methoxyphenylamino)-thiazole], on alcohol- and
      thermally oxidized sunflower oil-induced hyperlipidemia. Ethanol was given to
      animals at a dose of 5 ml of 20% solution and thermally oxidized sunflower oil at
      a level of 15% (15 g oil/100 g feed). Our results showed increased activity of
      aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl
      transferase (GGT) and increased levels of cholesterol, triglycerides and
      phospholipids in the plasma of groups given alcohol, thermally oxidized oil and
      alcohol + thermally oxidized oil when compared with normal control group. The
      levels of tissue (liver and kidney) cholesterol and triglycerides were increased
      significantly in groups treated with alcohol, thermally oxidized oil and alcohol
      + thermally oxidized oil when compared with normal control rats. The levels were
      decreased when DA was given along with alcohol and thermally oxidized oil. The
      level of phospholipids decreased significantly in the liver and kidney of rats
      administered alcohol, thermally oxidized oil and alcohol + thermally oxidized oil
      when compared with normal control rats. The level increased when DA was
      administered along with alcohol and thermally oxidized oil. The activity of
      phospholipase A and C increased significantly in the liver of groups given
      alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when
      compared with normal control rats, whereas the activity was decreased upon DA
      treatment. The obtained results indicate that DA can decrease the lipid levels in
      alcohol- and thermally oxidized oil-treated rats.

PMID- 15156075
TI  - Protective effect of S-allylcysteine and lycopene in combination against N-methyl
      N'-nitro-N-nitrosoguanidine-induced genotoxicity.
AB  - Chemoprotection by diet-derived antioxidants has emerged as a cost-effective
      approach in preventing genotoxicity and carcinogenicity. In this study, we
      investigated the protective effects of S-allylcysteine (SAC) and lycopene against
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity. Quantification
      of bone marrow micronuclei and chromosomal aberrations in male Wistar rats was
      used to monitor the protective effects of SAC and lycopene. Intragastric
      administration of MNNG (40 mg/kg) induced a significant increase in the frequency
      of micronuclei and chromosomal aberrations. Although pretreatment with SAC and
      lycopene significantly reduced the frequency of MNNG-induced bone marrow
      micronuclei and chromosomal aberrations, the combination of SAC and lycopene
      exerted a greater protective effect. These findings indicate that antioxidants
      such as SAC and lycopene, are effective chemoprotective agents against
      genotoxicity and carcinogenicity especially when used in combination.

PMID- 15156076
TI  - Ovine model for clear-cut study on the role of cholecystokinin in antral, small
      intestinal and gallbladder motility.
AB  - Cholecystokinin (CCK) is one of the major gastrointestinal hormones involved in
      the control of digestive tract and gallbladder motility. Its action involves
      several mechanisms. The ovine model was developed in order to further explore the
      role of CCK in gastric, small intestinal and gallbladder motility under various
      experimental conditions. Five Merino sheep were used with bipolar electrodes
      implanted to their antrum, entire small intestine and gallbladder as well as
      strain gauge force transducers were attached to the duodenum and gallbladder
      fundus, near the electrodes. In the course of chronic experiments, the
      myoelectric and motor activity were recorded by means of the adapted
      electroencephalograph. Among the variety of CCK-octapeptide or cerulein doses,
      three doses of each CCK peptide were selected and then applied for various time
      periods. Finally, the effects of the hormones administered within 30 s during
      phase 2 of the same or different migrating myoelectric complexes (MMCs) on
      gastrointestinal and gallbladder myoelectric and motor activity were studied in
      fasted and non-fasted animals. Injection of the highest dose inhibited rumination
      in four of the five sheep and inhibited phase 3 MMC in the antroduodenal region.
      Hormone administration inhibited dose-dependently antral myoelectric activity.
      The effects of moderate dose of both CCK peptides on myoelectric activity of the
      duodeno-jejunum was usually opposite (i.e. stimulatory) than that of the ileum.
      Gallbladder response to CCK peptides exhibited mostly the tonic character, and in
      some experiments, the slow wave frequency and amplitude were altered. It is
      concluded that CCK acts on several targets and different mechanisms underlie its
      multiple actions on gastrointestinal and gallbladder motility in sheep.

PMID- 15156077
TI  - Penetration of cotrimoxazole components into skin after a single oral dose.
      Theoretical versus experimental approach.
AB  - Concentrations of trimethoprim and sulfamethoxazole in plasma, cantharidin
      induced skin blister fluid and theoretical peripheral compartment were determined
      in twelve male subjects suffering from bacterial skin diseases after a single
      oral dose of 0.32 g of trimethoprim and 1.6 g of sulfamethoxazole. Maximum
      trimethoprim concentrations of 8.5 +/- 1.1 micromol/l in plasma, 5.6 +/- 0.8
      micromol/l in blister fluid and 5.8 +/- 2.2 micromol/l in theoretical peripheral
      compartment were found after 3 +/- 1, 7 +/- 2 and 9 +/- 6 h, respectively. Degree
      of penetration into blister fluid and theoretical peripheral compartment was 0.94
      +/- 0.23 and 1.05 +/- 0.09, respectively. The differences between respective
      pharmacokinetic parameters of trimethoprim in blister fluid and theoretical
      peripheral compartment were statistically insignificant. Maximum sulfamethoxazole
      concentrations of 295 +/- 47 micromol/l in plasma, 182 +/- 46 micromol/l in
      blister fluid and 239 +/- 58 micromol/l in theoretical peripheral compartment
      were found after 3 +/- 1, 8 +/- 2 and 7 +/- 4 h, respectively. Degree of
      penetration into blister fluid and theoretical peripheral compartment was 0.82 +/
      0.20 and 1.04 +/- 0.02, respectively. In contrast to trimethoprim, the
      differences between respective pharmacokinetic parameters of sulfamethoxazole in
      blister fluid and theoretical peripheral compartment, except time to maximum
      concentration, were statistically significant. Cantharidin-induced skin blister
      fluid method can be used to estimate drug penetration into skin. Due to
      differences between the respective pharmacokinetic parameters in experimental and
      theoretical peripheral compartment, in some cases evaluation of drug penetration
      into skin should not be replaced by the theoretical peripheral compartment
      calculation.

PMID- 15156078
TI  - Influence of selected cardiological drugs on oxidative status.
AB  - The aim of the study was to determine the effect of the often applied drugs in
      cardiovascular diseases (metoprolol, acetylsalicylic acid, simvastatin and
      molsidomine) on antioxidative/oxidative balance in vivo. The determination of
      oxidative status was based on measurements of concentration of: thiobarbituric
      acid reactive substances (TBARS - lipid peroxidation products), protein carbonyl
      groups (marker of proteins oxidative injury), nitrotyrosine (marker of NO
      mediated tissue damage) and sulfhydryl groups (protein oxidation product). The
      assays were performed in the plasma and whole blood of rabbits after three weeks
      of daily intragastric administration of the drugs mentioned above. It was shown
      that all drugs except acetylsalicylic acid caused an increase in the plasma and
      hemolysate levels of TBARS. No changes in nitrotyrosine concentration were
      observed after drug administration. The content of carbonyl groups did not change
      after administration of metoprolol, but increased significantly after simvastatin
      and molsidomine administration. Blood sulfhydryl group concentration was not
      changed by metoprolol but it significantly decreased after acetylsalicylic acid
      and increased significantly after molsidomine administration.

PMID- 15156079
TI  - Losartan may prevent the elevation of plasma glucose levels induced by chronic
      stress.
AB  - The effect of angiotensin II antagonist, losartan, on chronic stress-induced
      elevation of blood glucose levels was investigated in rats. Chronic
      immobilization stress caused an increase in blood glucose levels in rats.
      Administration of losartan (3 mg/kg, po) before stress exposure significantly
      prevented this increment. We suggest that losartan showed this effect by
      decreasing the excessive sympathetic response to stress. In conclusion, there is
      a relationship between stress, sympathetic nervous system, and renin-angiotensin
      system.

PMID- 15156082
TI  - Middle school children's participation in activities and the effects of pain from
      backpack use on participation.
AB  - PURPOSE: The purpose of this study was to explore the activities in which middle
      school students participate most often. This research also determined whether
      students reported having difficulty participating in specific activities because
      of musculoskeletal pain from using their backpack, and whether the pain impacted
      the frequency with which they participated in activities. METHOD: One hundred and
      twenty seven 7th grade students between the ages of 12 and 13 years old completed
      The Activity Participation Survey. This survey was used to determine the
      activities that students participated in most often and whether their
      participation was impacted by pain. Frequencies and independent samples t-tests
      were used to analyze the data. RESULTS: The results revealed that over 50% of
      students participated in work related activities such as completing homework,
      carrying books during school and completing household chores most often
      throughout the week. The results also indicated that 31.0% of the students
      reported having difficulty participating in activities as a result of pain.
      Nearly 25% of students reported having difficulty carrying their books during
      school because of pain, and 19% reported having difficulty playing sports. It is
      notable that among the students who reported having difficulty carrying their
      books, 12% reported carrying their books less frequently. CONCLUSIONS: Future
      studies should be performed to verify that pain from backpack use causes middle
      school students' participation in activities to be difficult. Continued research
      may further reveal that students may decrease the frequency that they engage in
      activities because of difficulty and pain, and results may be used to educate
      others on the scope and pertinence of this issue to students' daily lives.

PMID- 15156080
TI  - Effect of topiramate on mechanical allodynia in neuropathic pain model in rats.
AB  - Topiramate, unlike gabapentin, lamotrigine and tiagabine, resembles phenytoin and
      carbamazepine since it had been used as an antinociceptive drug in empirical
      treatment of neuropathic pain in humans, before its systemic and planned research
      was conducted in animal models of pain. Chronic administration of topiramate, at
      the dose of 50 mg/kg/day, significantly diminished the mechanical sensitivity and
      shortened the period of allodynia in the Seltzer mononeuropathy model in rats.

PMID- 15156083
TI  - Facilitators and barriers to employment: the perspectives of people with
      psychiatric disabilities and employment service providers.
AB  - This study examined the perspectives of people with psychiatric disabilities and
      employment service providers regarding factors that most directly help or hinder
      consumer efforts to obtain and maintain employment. Forty-four adults with
      serious mental illness (SMI) (consumers) and 30 providers participated in 12
      focus groups across Massachusetts. We began both consumer and provider groups by
      posing two broad questions: 1) what factors most help people with SMI get and
      keep jobs (facilitators), and 2) what factors most prevent people with SMI from
      getting and keeping jobs (barriers)? Data were analyzed qualitatively and both
      person and environmental factors were highlighted. Among facilitators,
      participants agreed that quality consumer-provider relationships and
      individualized employment services are most instrumental in helping consumers
      achieve employment goals. Participants identified a range of environmental
      barriers, including issues related to the service system, entitlement programs,
      non-human resources, and social stigma. Implications for services are discussed.

PMID- 15156084
TI  - Workers' compensation for psychological injury: personal and environmental
      correlates.
AB  - The aim of this study was to determine the personal and environmental factors
      that contribute to the lodging of a workers' compensation claim for psychological
      injury. Four groups were compared: individuals who had lodged a workers'
      compensation claim, people who had sought psychological assistance for the
      management of work-related stress reactions but who had not lodged a workers'
      compensation claim; people who had experienced stress symptoms but who had not
      lodged a claim or sought help; and people who experienced stressful work events
      but who had not developed symptoms. Examination was made of cognitive distortion,
      irrational beliefs and coping resources as individual factors, and stressful life
      events, daily hassles and work environment factors as environmental variables.
      The Compensation group was distinguished from other groups only on the basis of
      work environmental factors. The implications of these results in the
      understanding of the decision to lodge a workers' compensation claim are
      considered.

PMID- 15156085
TI  - Musculoskeletal injuries associated with selected university staff and faculty in
      an office environment.
AB  - A research team with backgrounds in occupational therapy, rehabilitation, policy
      and rulemaking, and prevention programs affecting occupational health and safety
      designed, validated, and analyzed an ergonomics survey of university staff and
      faculty. The purpose of the study was to validate identified risk factors from
      the literature contributing to work-related musculoskeletal disorders (WRMDs) in
      an office setting within a university setting. The study was also designed to
      determine differences between faculty and staff in the university setting and
      their exposure to physical risk factors to WRMDs. The results suggest faculty
      have their keyboard in awkward positions more frequently than staff, and staff
      had more experience with mechanical stress than faculty. The researchers
      recommend parameters for the design of a university ergonomics program based on
      employee and education, management commitment, medical case management, problem
      job identification, and development of solutions.

PMID- 15156086
TI  - Ergonomic recommendations and their role in cardiac sonography.
AB  - Musculoskeletal disorders (MSDs) have been recognized as a serious hazard to the
      health and safety of sonographers. Recommendations have been made on ways to
      reduce and prevent the frequency and severity of these disorders. The purpose of
      this study was to ascertain the impact ergonomics has had on the prevalence of
      MSDs among cardiac sonographers. Three hundred randomly selected Registered
      Diagnostic Cardiac Sonographers were surveyed. Eighty-one respondents completed
      the survey. The majority of the sample population was female with an average age
      of 40 and job tenure between 6-15 years. Ninety percent of respondents reported
      musculoskeletal pain/discomfort while scanning. Seventy-three percent of
      respondents perceived a need for ergonomic interventions. The majority of
      respondents were aware of previously recommended ergonomic interventions and had
      implemented what was feasible. Still, the experience of pain and discomfort, and
      incidence of MSDs remains exceptionally high for this occupation. It appears that
      recommended ergonomic interventions have not had a significant impact on
      improving the health and safety of cardiac sonographers.

PMID- 15156087
TI  - Development of the Health and Work Questionnaire (HWQ): an instrument for
      assessing workplace productivity in relation to worker health.
AB  - BACKGROUND: Workplace productivity evaluations often involve subjective
      assessments. This study was performed to develop and validate a new
      multidimensional instrument, the Health and Work Questionnaire (HWQ), for
      measuring workplace productivity and worker heath. METHODS: In a prospective, non
      randomized study, objective and subjective workplace productivity (measured with
      the HWQ) was assessed among 96 current, 94 former, and 104 non-smoking volunteer
      reservation agents at a US-based international airline. RESULTS: Six HWQ sub
      scales were identified from factor analyses: productivity, concentration/focus,
      supervisor relations, impatience/irritability, work satisfaction, and non-work
      satisfaction. Non-smokers (individuals who had never smoked) had higher scores on
      all scales. The HWQ scale scores all correlated significantly with the objective
      measure "Time Lost"; two of the scales correlated significantly with the summary
      objective performance measure. Magnitudes of the significant correlations were
      modest (0.12 to 0.22). CONCLUSIONS: The HWQ may be useful for evaluating the
      impact of interventions on workplace productivity. Additional validation research
      on the HWQ is recommended before use as a primary measure in studies of worker
      productivity.

PMID- 15156088
TI  - Development of activity monitoring for determining load carriage patterns in
      school students.
AB  - The loads that school students are carrying to, around and from school is an
      issue of increasing concern particularly as the long term effects of excessive
      load carriage on school students' musculoskeletal health is unknown. A greater
      understanding of the temporal patterns of students' load carriage, which usually
      involves backpacking, would assist in determining the magnitude of the problem
      that is faced by school students. The aim of this study was to determine the
      duration of school students' walking, running and stair climbing while
      backpacking and identify when students take off and put on their backpacks using
      activity monitoring and video, and therefore validate activity monitoring as a
      tool for measuring the temporal patterns of backpacking in school students. An
      activity monitor was secured in the backpacks of six school students while they
      completed a predefined physical activity course. Participants firstly completed
      the course following a set time pattern ('set course') and then repeated the
      course while performing activities as they pleased ('free course'). Video footage
      and activity monitor data were captured simultaneously. The activity monitor
      provided consistent visual differentiation between walking, running and taking
      off and putting on a backpack. The greatest variation between measures was for
      walking during the 'free course' (mean 8, SD 7 seconds), while the least
      variation between measures was for stair climbing during the 'set course' (mean
      3, SD 2 seconds). There were no statistical differences between the activity
      monitor and video camera determined durations for any of the activities. These
      preliminary results suggest that activity monitoring may enable valid analysis of
      the temporal patterns of backpacking with little disruption to the user, although
      more work is required to verify this.

PMID- 15156089
TI  - Effects of a work injury prevention program for housekeeping in the hotel
      industry.
AB  - OBJECTIVE: The aim of this retrospective study was to determine the effectiveness
      of a work injury prevention program in the housekeeping department of a hotel.
      Studies have validated the use of different injury prevention strategies to
      decrease the incidence of work-related injuries. Few studies, however, have
      reported the efficacy of an on-site work injury prevention program by a physical
      therapist. STUDY DESIGN: In 1995, implementation of a work injury prevention
      program by a physical therapist to 50 housekeeping supervisors, 60 house persons
      and 340 guest room attendants at a large hotel began. This program included a
      detailed work risk analysis of the work environment, development of job
      descriptions, identification of injury-related problematic work situations, and
      implementation of a job specific supervisor-training program. Supervisor, house
      person and guest room attendant training was also conducted at the end of 1995
      and the beginning of 1997. RESULTS: Data of injury reports in 1995, 1996, and
      1997 were analyzed to determine the results of the program. There was a reduction
      in total injury claims, total medical expenses, total lost work time and total
      restricted duty time. CONCLUSION: These results demonstrate the cost
      effectiveness of implementing a work injury prevention program for housekeeping
      guest room attendants in the hotel industry.

PMID- 15156091
TI  - Non-manipulation quantitative designs.
AB  - The article describes non-manipulation quantitative designs of two types,
      correlational and causal comparative studies. Both of these designs are
      characterized by the absence of random assignment of research participants to
      conditions or groups and non-manipulation of the independent variable. Without
      random selection or manipulation of the independent variable, no attempt is made
      to draw causal inferences regarding relationships between independent and
      dependent variables. Nonetheless, non-manipulation studies play an important role
      in rehabilitation research, as described in this article. Examples from the
      contemporary rehabilitation literature are included.

PMID- 15156090
TI  - Positive encounters with rehabilitation professionals reported by persons with
      experience of sickness absence.
AB  - More knowledge is needed on different factors that can promote return to work
      among sick-listed persons. One such factor might be by their interactions with
      the rehabilitation professionals they encounter. The aim of the present study was
      to identify and analyze statements about positive encounters with rehabilitation
      staff, reported by persons who had been absent from work with back, neck, or
      shoulder diagnoses. A descriptive and explorative qualitative approach was used
      to analyze data from five focus-group interviews. There were few statements on
      positive encounters, and they were frequently attributed to sheer luck.
      Experiences of positive encounters were assigned to two major categories:
      respectful treatment and supportive treatment. Receiving adequate medical
      examination or treatment was also mentioned as being positive. Further efforts
      are needed to study and develop methods for investigating interactions with
      rehabilitation professionals that laypersons experience as positive and that may
      contribute to empowerment and influence return to work when sickness absent.

PMID- 15156092
TI  - Central distribution of vestibular afferents that innervate the anterior or
      lateral semicircular canal in the mongolian gerbil.
AB  - The central distribution of afferents that innervate the crista ampullaris of the
      anterior or lateral semicircular canals was determined in gerbils following the
      direct injection of tracers into one sensory neuroepithelia. Labeled somata were
      scattered throughout the superior ganglion. The central distribution of fibers
      demonstrated extensive overlap. The central branch of afferents innervating
      either canal was located in the rostral part of the nerve. Nerve fibers divided
      into ascending and descending branches. Ascending branch ramifications terminated
      in the superior vestibular nucleus, the magnocellular and parvicellular medial
      vestibular nuclei, and the cerebellum. Cerebellar terminal areas include the
      flocculus, nodulus and uvula. Descending branch ramifications terminated in the
      caudal medial, parvicellular medial and descending vestibular nuclei, and the
      nucleus prepositus hypoglossi. Lateral canal afferents terminated sparsely in
      nucleus cuneatus. The anterior canal had sparse innervation in the paratrigeminal
      and gigantocellular reticular formation. This study has shown many similarities
      in the central distribution of fibers that innervate the anterior and lateral
      canals and a few areas of segregated input. Projections outside the vestibular
      nuclei are more extensive than previously determined, including afferents to
      prepositus hypoglossi, cochlear nuclei, and reticular formation. Projections to
      the flocculus appear as numerous as those to the vermis.

PMID- 15156093
TI  - Interaction of vestibular, echolocation, and visual modalities guiding flight by
      the big brown bat, Eptesicus fuscus.
AB  - The big brown bat (Eptesicus fuscus) is an aerial-feeding insectivorous species
      that relies on echolocation to avoid obstacles and to detect flying insects.
      Spatial perception in the dark using echolocation challenges the vestibular
      system to function without substantial visual input for orientation. IR thermal
      video recordings show the complexity of bat flights in the field and suggest a
      highly dynamic role for the vestibular system in orientation and flight control.
      To examine this role, we carried out laboratory studies of flight behavior under
      illuminated and dark conditions in both static and rotating obstacle tests while
      administering heavy water (D2O) to impair vestibular inputs. Eptesicus carried
      out complex maneuvers through both fixed arrays of wires and a rotating obstacle
      array using both vision and echolocation, or when guided by echolocation alone.
      When treated with D2O in combination with lack of visual cues, bats showed
      considerable decrements in performance. These data indicate that big brown bats
      use both vision and echolocation to provide spatial registration for head
      position information generated by the vestibular system.

PMID- 15156094
TI  - Cortical vestibular representation in the superior temporal gyrus.
AB  - We present the unique case of a patient with a circumscribed solitary cerebral
      metastasis of a malignant melanoma extending from the medial part of the superior
      temporal gyrus to the lower part of the 1st long insular gyrus causing gait and
      stance instability and an ipsiversive tilt of the subjective visual vertical.
      Oculomotor disorders could not be detected. We suggest that the superior temporal
      gyrus is likely to be involved in spatial orientation presumably using otolithic
      information.

PMID- 15156095
TI  - Postural instability in Meniere's disease.
AB  - In order to characterize the postural instability by duration of Meniere's
      disease (MD) we present the results of 180 MD patients tested on posturography.
      The duration of the disease varied from 4 weeks to 36 years. The patients were
      clinically examined and they had filled a questionnaire concerning their
      symptoms. Postural instability was examined by a force platform posturography and
      the results are expressed as sway velocities (SV). There was no statistically
      significant difference in the mean SV between groups of different duration of MD.
      The number of the patients with normal eyes open SV declined by duration of the
      illness from 73% to 38% but the decline was not statistically significant. The
      mean age in the different duration groups of MD varied from 47 to 61 years. In
      general 58% of the patients had their eyes open SV in normal range and 55% when
      measured eyes closed. When examining the SV between the 4 different hearing
      stages of MD we found that those belonging into the group III (pure tone average
      [PTA] 41-70 dB) had significantly higher eyes open and eyes closed SV's than the
      patients in the group I (PTA under 25 dB).

PMID- 15156096
TI  - Prevalence of dizziness and vertigo in an urban elderly population.
AB  - The prevalence of balance symptoms (vertigo, dizziness, and dysequilibrium) was
      investigated in an epidemiological study of elderly people, the longitudinal and
      cross-sectional gerontological and geriatric population study from Goteborg,
      Sweden (H70). Three different age cohorts were studied, one at age 70, one at age
      75 and one at ages 79, 82, 85, 88 and 90 years. Altogether 2011 participants
      answered the questionnaire at 3197 occasions. The overall prevalence of balance
      problems at age 70 was 36% (women) and 29% (men). Balance symptoms were more
      common among women than men, and increased with increasing age. At ages 88-90
      years the corresponding values were 51-45%. The most common symptom was poor
      balance/general unsteadiness (11-41%). Rotatory symptoms occurred in 2-17%. Other
      types of symptoms were less common. Precipitating factors were rising from supine
      to sitting position in 17-40%. Balance symptoms in a side position were uncommon,
      but occurred more often when tilting the head backwards (up to 14%). Signs that
      possibly could indicate neurological involvement were uncommon. Falls in
      conjuncture to dizziness, vertigo and similar symptoms occurred in 7-15%, in
      about equal proportions indoors as outdoors.

PMID- 15156097
TI  - Chlorpheniramine for motion sickness.
AB  - BACKGROUND: Motion sickness remains a significant problem for travelers and for
      those involved in naval, aviation and space operations. Many motion sickness
      remedies are also sedating, making them undesirable in many settings. METHODS: We
      studied chlorpheniramine as a potential motion sickness treatment. A placebo
      controlled, double-blind, dose-ranging trial was performed to establish the most
      effective dose and the drug's effects on cognition. Eighteen normal, motion
      sickness susceptible subjects received placebo, low dose (4 mg) or high dose (12
      mg) chlorpheniramine 3.5 hours before off-axis vertical rotation. Cognitive
      testing included a battery of objective and subjective tests performed before
      drug ingestion, at peak drug effect and following rotation. RESULTS:
      Chlorpheniramine significantly increased the time in the chair compared to
      placebo at high dose (7.2 minutes to 11.7 minutes) and low dose (7.2 minutes to
      10.2 minutes). Chlorpheniramine did not affect performance on objective cognitive
      tests. Subjects reported significantly more sleepiness and less alertness with
      high-dose chlorpheniramine, although they could not reliably determine when they
      had received active drug. CONCLUSION: Chlorpheniramine is effective and could be
      considered for use against motion sickness. Chlorpheniramine also has the
      potential to be administered transdermally.

PMID- 15156098
TI  - Predicting antigenic peptides suitable for the selection of phage antibodies.
AB  - Selection from phage antibody libraries can be considered to be an in vitro
      immune system in which the antibody response is reduced to the bare minimum of
      antigen recognition. Using selections of antibodies on peptides from a phage
      antibody library, we investigated what constitutes peptide antigenicity in the
      context of the antibody-protein binding site. We selected polyclonal antibodies
      in a high throughput format against 44% of 90 overlapping peptides derived from
      three different proteins. Of these, 33% of peptides (epitopic peptides) were able
      to select antibodies that recognized the protein from which the peptides were
      derived. Although no algorithm was able to predict all epitopic peptides, solvent
      accessibility was the best predictor in this cell-free antibody selection
      context. We subsequently applied solvent accessibility to successfully predict
      epitopic peptides from p53 and Znf217, and showed that such peptide selected
      single-chain antibodies were able to recognize soluble p53 in ELISA and Znf217 in
      a western blot. This is likely to have considerable utility in functional
      genomics and proteomics where it should be possible to select antibodies against
      gene products on the basis of deduced amino acid sequence in a high throughput
      fashion.

PMID- 15156099
TI  - Immunoglobulin repertoire of B lymphocytes infiltrating breast medullary
      carcinoma.
AB  - Tumor specific peptides recognized by T lymphocytes infiltrating solid tumors, as
      well as the corresponding T cell receptor (TcR) repertoire usage, have been
      extensively investigated. By contrast, tumor infiltrating B cells and their
      immunoglobulin (Ig) repertoire have been studied only in a limited number of
      tumors. The objective of the present study was to determine, whether DNA sequence
      analysis of the expressed immunoglobulin variable regions of B cells that
      infiltrate breast cancer, could be used to reveal a potential specific tumor
      binding capacity of the antibodies. To answer this question, about 200 expressed
      Ig heavy (VH) and light chain variable gene (VL) regions were cloned, sequenced
      and comparatively analysed from a typical medullary beast carcinoma (MBC), where
      the massive B and plasma cell infiltration correlates with favourable prognosis
      despite of its high grade. The tumor infiltrating B cell Ig heavy and light chain
      sequences could be classified into clusters, families and subgroups, based on the
      identity level to germline, showing a pattern of oligoclonality. Some
      overrepresented clusters could be determined. In the course of a detailed
      analysis and search in Blastn database, a number of VH and VL sequences showed
      more than 99% homology to DNA sequences of Ig VH region, with proved tumor
      antigen binding capacity. Our data suggest, that potential tumor binder Ig VH and
      VL sequences might be selected using a detailed immunoglobulin variable region
      analysis. This new approach might have a benefit for further antibody
      engineering, as difficulties in search for tumor binders by phage library
      selection might be reduced and the time for selection shortened.

PMID- 15156100
TI  - Immunohistochemical assay (IHC) to study C-erbB-2 status of breast cancer using
      monoclonal antibody CIBCgp185.
AB  - The C-erbB-2 proto-oncogene encodes a 185KD glycoprotein with tyrosine kinase
      activity. Overexpression of this gene either due to gene amplification and/or
      increased transcription has been observed in a variety of cancers and has been
      associated with more aggressive disease and a poor clinical prognosis in 20-30%
      of patients with breast cancer. Besides several prognostic factors like tumor
      size, histologic grade, steroid hormone receptor status, DNA ploidy, lymph node
      status etc which are significant in the management of breast cancer, C-erbB-2
      status might also serve as an additional parameter. Immunohistochemistry is the
      most widely used method to study the expression of C-erbB-2 in breast cancer. The
      very low levels of expression of C-erbB-2 by normal tissues makes this receptor,
      a potential target for diagnosis and therapy with monoclonal antibodies raised
      against its extracellular domain. One such monoclonal antibody designated as
      CIBCgp185 of IgG2a isotype has been generated in our laboratory and extensively
      characterized. In the present study, an indirect immunohistochemical assay was
      carried out on frozen tumor tissue sections of 127 malignant breast tumor
      specimens of various histological types using monoclonal antibody CIBCgp185,
      which revealed intense staining of tumor cell membrane in 32 specimens,
      indicating overexpression of C-erbB-2. In the case of 53 benign breast tissues
      and 24 normal breast tissues studied, this MAb did not exhibit any reactivity.
      These results suggest that MAb CIBCgp185 might prove useful to identify tumors
      with overexpression of C-erbB-2 which are often associated with poor prognosis
      and early recurrence and might have future therapeutic application in the
      treatment of these cancers.

PMID- 15156101
TI  - Neutralizing monoclonal antibody against anthrax lethal factor inhibits
      intoxication in a mouse model.
AB  - Anthrax toxin is the dominant virulence factor of Bacillus anthracis; drugs
      blocking its action could therefore have therapeutic benefit. We report here the
      production of a neutralizing monoclonal antibody (mAb) against anthrax lethal
      factor (LF) and the inhibition by the antibody of anthrax lethal toxin (LeTx)
      formation. The anti-LF monoclonal antibody LF8 neutralized the LeTx challenge
      both in vitro with macrophage J774A.1 cells and in vivo in nude mice. Our data
      suggested that LF8 binds LF at or near the PA binding domain. A set of
      dodecameric peptides was selected from a phage-displayed peptide library through
      their specific binding to anti-LF neutralizing mAb LF8. These small peptides
      compete with LF to bind LF8. Further investigation is undergoing to test the
      potential application of these peptides to the clinical treatment of anthrax
      infection by blocking LeTx formation.

PMID- 15156102
TI  - mRNA expression of AgSK1, an adenocarconoma-associated antigen, in tumor tissue
      of patients with colorectal cancer: Quantitative RT-PCR analysis.
AB  - PURPOSE: SK1, a human IgM monoclonal antibody recognizes the antigen, termed
      AgSK1 which was shown to be preferentially expressed by human adenocarcinomas,
      particularly human gastrointestinal malignancies. The aim of this study was to
      clarify the clinicopathological significance of AgSK1 mRNA expression in human
      colorectal cancer. METHODS: Using a quantitative RT-PCR, we studied the mRNA
      expression level of AgSK1 in the resected specimen of 40 patients with colorectal
      cancer. We estimated the tumor tissue value (T-value), nontumorous tissue value
      (N-value), and the ratio of T-value to N-value (T/N Ratio). For further analysis,
      we compared these data with the clinicopathological features. RESULTS: In the
      status of lymph node metastases, pN positive status tended to have a higher T
      value level of AgSK1 mRNA than pN negative status (P = 0.076). According to a
      mean T-value (8.032) or a mean T/N Ratio (1.549), we divided these patients into
      two groups, low expression group and high expression group. A high expression
      group showed a significantly higher frequency of positive lymph node metastases
      (T-value; P = 0.021, T/N Ratio; P = 0.024). CONCLUSION: AgSK1 mRNA expression in
      tumor tissue may become a useful marker for lymph node metastases and a malignant
      potential marker of colorectal cancer.

PMID- 15156104
TI  - Design optimization of functionally graded dental implant.
AB  - The continuous increase of man's life span, and the growing confidence in using
      artificial materials inside the human body necessities introducing more effective
      prosthesis and implant materials. However, no artificial implant has
      biomechanical properties equivalent to the original tissue. Recently, titanium
      and bioceramic materials, such as hydroxyapatite are extensively used as
      fabrication materials for dental implant due to their high compatibility with
      hard tissue and living bone. Titanium has reasonable stiffness and strength while
      hydroxyapatite has low stiffness, low strength and high ability to reach full
      integration with living bone. In order to obtain good dental implantation of the
      biomaterial; full integration of the implant with living bone should be
      satisfied. Minimum stresses in the implant and the bone must be achieved to
      increase the life of the implant and prevent bone resorption. Therefore, the aim
      of the current investigation is to design an implant made from functionally
      graded material (FGM) to achieve the above advantages. The finite element method
      and optimization technique are used to reach the required implant design. The
      optimal materials of the FGM dental implant are found to be
      hydroxyapatite/titanium. The investigations have shown that the maximum stress in
      the bone for the hydroxyapatite/titanium FGM implant has been reduced by about
      22% and 28% compared to currently used titanium and stainless steel dental
      implants, respectively.

PMID- 15156103
TI  - Introduction of polyethylene terephthalate mesh (KoSa hochfest) for abdominal
      hernia repair: an animal experimental study.
AB  - BACKGROUND: Nowadays the surgical treatment of abdominal hernias includes the use
      of synthetic meshes in most cases. Due to chronic foreign body reactions,
      however, the most commonly used polypropylene meshes can lead to material
      hardening and recurrent hernias. As a proven cruciate ligament replacement
      polyethylene terephthalate (KoSa hochfest showed only little foreign body
      reactions and provided excellent clinical outcomes. In an animal trial it was
      therefore tested as mesh implant for hernia treatment and compared with Prolene.
      MATERIAL AND METHOD: The study was carried out in 12 mini-pigs. 10 x 10 cm of the
      musculofascial abdominal layer was resected, the peritoneum was preserved. A 15 x
      15 cm synthetic mesh was implanted in sublay-technique (either KoSa hochfest,
      Telos GmbH, Marburg, Germany or Prolene, Ethicon, Norderstedt, Germany), mainly
      to test for chronic foreign body reactions. An independent pathologist tested the
      mesh size and foreign body reaction at 2 and 6 months, analysing the number of
      foreign body giant cells. RESULTS: No significant differences in mesh size were
      observed, neither between the compared groups nor with respect to the time
      periods. Compared to KoSa hochfest the foreign body reaction was significantly
      stronger in the Prolene implants, both at 2 and at 6 months (number of foreign
      body giant cells at 2 months: Prolene/KoSa hochfest: 2.2 +/- 0.4/0.8 +/- 0.2, at
      6 months: 4.6 +/- 1.3/1.1 +/- 0.5). In contrast to KoSa hochfest, Prolene still
      showed significant foreign body reactions at 6 months as well as calcifications
      of all samples. CONCLUSION: The animal trials revealed that due to its high
      biocompatibility and little foreign body reaction KoSa hochfest is a promising
      implant for the treatment of hernias.

PMID- 15156105
TI  - Changes in the contact area during the bedding-in wear of different sizes of
      metal on metal hip prostheses.
AB  - In metal on metal hip prostheses, the contact mechanics can influence the
      lubrication and wear rate. In particular, during the bedding-in wear, the contact
      area gradually increases to an optimal value, and the wear rate reduces as the
      contact stress reduces and the lubrication conditions improve. Geometrical
      designs that reduce the volume of bedding-in wear as the optimal contact area
      develops are preferable. The objective of this study was to analyse the wear
      volume as a function of contact area during the bedding-in period, with the aim
      of identifying geometrical design configurations that give lower bedding-in wear.
      As the radial clearance was reduced, the bedding-in wear volume to reach an
      optimal contact area also reduced. For a fixed radial clearance, increasing the
      head diameter also reduced the bedding-in wear volume.

PMID- 15156106
TI  - An integrated force-position tactile sensor for improving diagnostic and
      therapeutic endoscopic surgery.
AB  - This paper reports on the design, fabrication, testing, and modeling of a novel
      semiconductor microstrain gauge endoscopic tactile sensor. The designed assembly
      consists of two semiconductor microstrain gauge sensors, which are positioned at
      the back-face of a prototype endoscopic grasper. The sensor can measure, with
      reasonable accuracy, the magnitude and the position of an applied load on the
      grasper. The in-house electrical amplification system for the microstrain gauges
      is also designed, fabricated, and tested. The intensity of the magnitude of the
      applied force to the endoscopic grasper can be visually seen on a light emitting
      diode (LED) device. In total, 20 different force magnitudes, from 0.5 to 10 N
      with an increment of 0.5 N, for 7 different locations of the endoscopic grasper
      were tested experimentally. The sensor exhibits high force sensitivity, large
      dynamic range, and good linearity. It is insulated and can operate safely in wet
      environments. A 3-dimensional finite element modeling (FEM) is used to predict
      the behavior of the designed system under various loading conditions. There is a
      good correlation between the theoretical predictions of the force magnitudes and
      their points of application, which are computed by FEM, and experimentally
      obtained results. Potentially, the miniaturized electronic device could be
      integrated with an endoscope and the complete system could be used in operating
      rooms.

PMID- 15156107
TI  - Numerical simulations of stenosed femoral artery with symmetric 2-way bypass
      graft.
AB  - The numerical simulation of the conventional 1-way bypass graft and the presented
      2-way bypass graft used in the stenosed femoral arteries were completed. Purpose
      of the present study was to ascertain whether the modified geometry configuration
      of 2-way bypass graft could improve the flow conditions of femoral bypass graft.
      The physiological flows in 1-way and 2-way models were simulated with finite
      element method under the same calculation conditions. Comparisons were made
      between the hemodynamics of 1-way and 2-way models. The results suggested that 2
      way bypass graft could result in more favorable and regular flow conditions than
      1-way bypass graft, and could decrease the probability of intimal hyperplasia,
      restenosis and surgery failure in femoral bypass graft.

PMID- 15156108
TI  - Automatic recognition of small cell carcinoma based on the self-organizing neural
      network.
AB  - In this paper the recognition of Small Cell Carcinoma (SCC) is studied. For each
      type we select 128 samples for training, and randomly measure 200 cells in each
      sample. We introduce multi-scale morphology based on centroid coordinates to
      extract the boundaries of nuclei and obtain feature images of nuclei. The
      features of lung cancer cells are described by morphological and colorimetrical
      parameters, which is valuable to recognize SCC. Then the architecture of self
      organizing feature mapping (SOFM) neural network is studied for recognition of
      SCC. The weights of the network are adjusted by self-organizing competition, and
      finally inputted patterns are classified. This algorithm has the advantage of
      parallelism and fast-convergence, and may simplify the analysis of SCC. Clinical
      experiment results show that the correctness ratio of this system may reach 95.3%
      while recognizing lung cancer cell types. Our work is significant to the
      pathological researches of lung cancer, assistant clinic diagnosis, and
      assessment of therapeutic effects. Meanwhile a software system named as SCC. LUNG
      is established for automatic analysis.

PMID- 15156109
TI  - Degradation behaviour in vitro for poly(D,L-lactide-co-glycolide) as drug
      carrier.
AB  - Biodegradable polymers have been extensively investigated because of regulating
      drug release rate easily, obviating the need to remove the device, and good
      biocompatibility. Among the biodegradable polymers currently under investigation,
      poly(D,L-lactide-co-glycolide) (PLGA) copolymers are the most widely studied
      because of their long history of safe clinical use as drug carrier. 50 : 50 PLGA
      was used as a model degradable polymer in this study to investigate the
      degradation behaviour on drug release from bulk degradable polymers in vitro. 5
      fluorouracil (5-FU) was used as a model drug. Molecular weight change, residual
      mass, water uptake, morphological change of PLGA wafers, and pH of release test
      medium were characterized to investigate the effect of polymer degradation on
      drug release. The release rate of 5-FU increased with the increase of 5-FU
      loading amount and the release profiles of 5-FU irrespective of 5-FU loading
      amount followed near first order release kinetics.

PMID- 15156110
TI  - Feasibility study of custom hip stem design based on X-ray films.
AB  - The hip stem design based upon X-ray films requires sufficient information in
      order to customize for the patient. If the errors are resulted from rotating
      angles, more X-ray films may carry out the solution. The present study aimed to
      realize the improvement of multiple X-ray films for hip stem design. Eight X-ray
      films were taken from a volunteer. The characteristic length of X-ray film was
      input into cosine function to derive the relative rotating angle of each X-ray
      film. The combinations of 2, 4, 6, and 8 X-ray films that included true AP view
      and lateral view were obtained to construct the corresponding stem. CT images
      were used to construct femur and stem model to verify the rotating angle of femur
      in each X-ray film. A quantitative comparison was made between the hip stems for
      the fill ratio, fit gap and contact area. The results showed that the markers on
      the body surface would result in error and were unable to provide reference to
      the rotating angle of femur. The contact area and fill ratio of the stems
      designed by 6 or 8 X-ray films would get closer to that by CT images. It is
      concluded that the rotation of the femur could be determined from the length of
      femoral neck as well as the distance between the tips of medial and lateral
      condyles. The use of 6 or more X-ray films for custom-made hip stem as a source
      of design is recommended in this study.

PMID- 15156111
TI  - Influences of the temporal nature of the applied load and the tibial baseplate
      material on the stress distribution in a three-dimensional model of the human
      knee joint containing a prosthetic replacement.
AB  - The finite element analysis method was used to determine the stresses in all
      sections of a three-dimensional model of the proximal section of the human knee
      joint into which was cemented two parts of a total knee joint replacement (the
      tibial tray and the tibial baseplate), fully constrained at its distal end, and
      subjected to a total compressive joint force of 2 kN acting on points
      corresponding to the condyles. When the mean values of these stresses were
      computed for all sections of the model, two important trends were seen. First,
      when the load was applied dynamically, the stresses were between 1 and 20%
      different than when it acted quasi-statically. Second, regardless of how the load
      was applied, the stresses when the tibial baseplate was considered fabricated
      from ultra-high-molecular-weight polyethylene ranged from about 40% lower to
      about 320% higher compared to when Ti-13Nb-13Zr alloy was used. The significance
      of these findings as well as the limitations of the study are discussed.

PMID- 15156112
TI  - Detraining effects on the mechanical properties and morphology of rat tibiae.
AB  - To study bone adaptation to detraining in growing rats, nine weeks-old immature
      female Wistar rats (n=110) were subjected to treadmill running programs (30 or 60
      minutes-a-day) for up to 15 weeks, followed by unrestricted cage activities for
      the subsequent 15 weeks. The results revealed that (1) the cross-sectional area
      and mechanical properties of the midshaft bone significantly increased in
      response to running exercise, (2) its structural properties remained unchanged
      after the cessation of exercise, whereas the material properties returned to
      control level at a relatively early stage, (3) in the metaphysis, cortical bone
      area remained unchanged but trabecular bone area decreased in response to running
      exercise, (4) both areas slightly increased after the cessation of exercise, and
      (5) the changes in the mechanical properties and morphology of bone depended upon
      the repetition number and/or the duration of exercise, and were larger with
      longer duration of exercise.

PMID- 15156113
TI  - [Clinical and pathological significance of the genetic analysis in colorectal
      carcinomas].
AB  - The molecular genetics of colorectal carcinomas are among the best understood of
      common human cancers. Three inter-related molecular pathways are involved. The
      chromosomal instability pathway begins with inactivation of the APC/beta-catenin
      genes followed by activation of oncogenes and inactivation of additional
      suppressor genes, commonly with high frequency of allelic losses, cytogenetic
      abnormalities. The microsatellite instability pathway begins with inactivating
      one of a group of genes responsible for DNA nucleotide mismatch repair leading to
      extensive mutations in both repetitive and non-repetitive DNA sequences with low
      frequencies of allelic losses and rare alteration of tumor DNA content. Finally,
      the CpG island methylation pathway involves inactivation of genes by methylation
      of cytosines in promoter regions to silence gene expression without DNA sequence
      alterations. Molecular genetics have the potential for clinical applications.
      Combination of genetic classification of high levels of microsatellite
      instability (MSI-H), gene expression analysis of mismatch repair genes and
      subsequent mutation analysis of inactivated genes can be used as an effective
      method for the identification of hereditary nonpolyposis colorectal carcinoma
      patients. Molecular genetic alterations have been proposed to be of prognostic
      value, including allelic deletion on chromosome 18q, and on chromosome 17p. MSI-H
      has been reported as a marker for better prognosis. Individualizing
      chemoradiation by use of predictive markers for response or resistance to therapy
      is important in patients with advanced disease or candidacy for adjuvant therapy.

PMID- 15156114
TI  - [The changes of ammonia and epidermal growth factor concentration in gastric
      juice before and after the Helicobacter pylori eradication].
AB  - BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is the cause of peptic
      ulcer diseases, and gastric cancer. Hydrolysis of urea generating ammonia may
      cause cytotoxic effects on the gastric epithelium. The ammonia may induce the
      synthesis of epidermal growth factor (EGF) in gastric epithelium as an adaptive
      cytoprotective mechanism. The first aim was to examine the concentration of
      ammonia and EGF in gastric juice before and after H. pylori eradication in
      functional dyspepsia patients. The second aim was to examine the correlation
      among ammonia concentration, EGF concentration, and inflammatory score of
      gastritis. METHODS: The concentration of ammonia and EGF were measured by ELISA.
      The grade and severity of gastritis were measured according to the updated Sydney
      system. RESULTS: The concentration of ammonia in gastric juice was much higher in
      the H. pylori positive subjects (10,787 +/- 6,584 micro mol/L) than in the
      negative subjects (2,339 +/- 1,158 micro mol/L, p<0.0001). The concentrations of
      EGF in gastric juice was much higher in the positive subjects (1,462 +/- 393
      pg/mL) than in the negative subjects (1,088 +/- 499 pg/mL, p<0.005). The
      concentration of ammonia and EGF in gastric juice showed significant correlation
      (r=0.63, p<0.0001). The concentrations of ammonia and histologic severities
      showed significant correlation (r=0.41, p<0.0001). Moreover, the level of EGF in
      gastric juice and histologic severities showed positive correlation (r=0.20,
      p<0.005). CONCLUSIONS: As the concentration of ammonia in gastric juices
      increased, the concentration of EGF was also increased in functional dyspepsia
      with H. pylori infection. The concentration of EGF in gastric juice may play a
      role in the adaptive cytoprotection in H. pylori- induced gastritis.

PMID- 15156115
TI  - [Role of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor
      (PPAR) in gastric cancer].
AB  - BACKGROUND/AIMS: Gastric cancer is still the most frequently diagnosed malignancy
      in Korea. It has been reported that COX-2 and PPAR are involved in multi-step
      gastric carcinogenesis. The aim of the present study was to examine the
      expression of COX-2 and PPAR in gastric cancer. METHODS: A total of 75 subjects
      including 45 patients with gastric cancer and 30 controls were enrolled. All
      subjects underwent upper gastrointestinal endoscopic examination with tissue
      collection. mRNA extraction from the tissues and real-time PCR for COX-2, PPAR
      delta, and PPAR-gamma were performed. Gastric mucosal concentration of PGE2,
      which is a final product of COX-2, and 15d-PGJ2, which is a ligand of PPAR-gamma,
      were measured by the enzyme immunoassay method. RESULTS: COX-2 mRNA expression
      was significantly higher in both early gastric cancer tissues (EGC, 8.32 +/- 4.84
      micro gram/micro L, p<0.005) and advanced gastric cancer tissues (AGC, 8.16 +/-
      2.67 micro gram/micro L, p<0.001) than in non-cancerous tissues of controls (3.46
      +/- 1.72 micro gram/micro L). There was no significant difference of PPAR-delta
      and PPAR-gamma mRNA expression between gastric cancer tissues and controls.
      Mucosal PGE2 concentration was significantly higher in both EGC tissues (5.31 +/-
      0.49 micro gram/mg protein, p<0.001) and AGC tissues (5.46 +/- 0.54 micro gram/mg
      protein, p<0.001) than in non-cancerous tissues of controls (4.22 +/- 0.8 micro
      gram/mg protein). There was no significant difference of 15d-PGJ2 concentration
      between gastric cancer tissues and controls. CONCLUSIONS: COX-2 overexpression
      and increased PGE2 concentration in gastric tissues may play an important role in
      gastric carcinogenesis. However, the role of PPAR (delta and gamma) and 15d-PGJ2
      in gastric carcinogenesis is uncertain. Further studies are needed.

PMID- 15156116
TI  - [The safety and usefulness of endoscopic polypectomy for treatment of Brunner's
      gland adenomas].
AB  - BACKGROUND/AIMS: Brunner's gland adenoma is a rare benign tumor of the duodenum.
      Although several cases of successful endoscopic polypectomy have been reported,
      the studies on the safety and usefulness of endoscopic polypectomy are extremely
      rare. Therefore, we report the results of 10 cases of Brunner's gland adenoma
      treated by endoscopic polypectomy. METHODS: Between November 1998 and January
      2003, 10 cases of Brunner's gland adenoma were diagnosed. The mean age of the
      cases (6 male, 4 female) was 60.4 years. They were located in the bulb (9) and
      the second portion (1) of the duodenum. All cases were diagnosed and removed by
      endoscopic polypectomy. RESULTS: The size of the tumor ranged from 1.0 to 3.5 cm
      in diameter. Pedunculated polyps were found in three cases. In other seven cases,
      semipedunculated polyps were observed and, three of them were presented as
      submucosal tumor. All cases had no malignant foci. There was no complication such
      as bleeding, perforation, and pancreatitis after endoscopic polypectomy. During
      follow-up period (range 1~39 months) after endoscopic polypectomy, there was no
      complication and recurrence of the lesions. CONCLUSIONS: Endoscopic polypectomy
      was a safe and useful method for the treatment of duodenal Brunner's gland
      adenoma without complication and recurrence.

PMID- 15156117
TI  - Dose ascites mean more severe Crohn's disease?
AB  - BACKGROUND/AIMS: Ascites that can be induced by various causes is not a rare
      finding in Crohn's disease. The clinical implication of ascites in Crohn's
      disease remains unknown in the cases without any specific cause of ascites except
      Crohn's disease itself. The purpose of this study was to investigate the clinical
      implication and characteristics of ascites in Crohn's disease. METHODS: We
      reviewed the medical records of the patients with Crohn's disease who underwent
      abdominal CT scan. Patients were categorized into two groups: patients with
      ascites (22 cases) and without ascites (23 cases). We compared clinical features,
      disease activities and clinical courses of the two groups. RESULTS: Serum albumin
      level was significantly lower and the C-reactive protein level was significantly
      higher in the ascites group than in the control group. Harvey and Bradshaw index
      was significantly higher in the ascites group (8.32 +/- 2.51) than in the control
      group (6.09 +/- 2.07) (p=0.002). The average dose of prednisolone was higher in
      the ascites group. On the other hand, there was no significant difference in the
      number of cases requiring surgery due to complication between two groups.
      CONCLUSIONS: Our results suggest that the presence of ascites in Crohn's disease
      is associated with increased disease activity and inflammations requiring more
      aggressive treatment.

PMID- 15156118
TI  - [An analysis on the amount of excreted pancreatic juice after
      pancreatoduodenectomy].
AB  - BACKGROUND/AIMS: There has been lack of data on the secretion of the pancreatic
      juice after pancreatoduodenectomy. Thus, surgeons have difficulties in predicting
      the clinical sequences of pancreaticojejunostomy leakage or other pancreatic
      surgery. METHODS: This study employed 15 patients who underwent pylorus
      preserving pancreatoduodenectomy (PPPD) with total external drainage of the
      pancreatic duct from January 2000 to June 2001. RESULTS: These patients were
      divided into the normal pancreas group (n=11) and chronic pancreatitis-
      accompanied group (n=4). Excretion of pancreatic juice was suppressed in a few
      days after PPPD. Then, it gradually increased and became constant at the
      postoperative day 4. The amount of excreted pancreatic juice in the normal
      pancreas group was 229 +/- 99, 85~385 (mean, range) mL/day at the postoperative
      day 7 before the initiation of oral intake, and was increased to 314 +/- 222,
      110~910 (mean, range) mL/day at the 7th day after the initiation of food intake.
      The usage of octreotide during early fasting period had no influence on the
      excretion of the pancreatic juice in the normal pancreas group. CONCLUSIONS: We
      observed the real amount of secreted pancreatic juice after PPPD. These data may
      be helpful to interpret and manage the postoperative conditions such as
      pancreatic leakage or pancreatic exocrine insufficiency.

PMID- 15156119
TI  - [A case of Kaposi's sarcoma associated with ulcerative colitis].
AB  - Kaposi's sarcoma is a rare and slowly progressive disease that primarily affects
      the skin but has an associated visceral involvement. It can occur in the HIV
      positive patients or patients treated with immunosuppressants. However, it is
      extremely rare in the patients receiving the treatment for inflammatory bowel
      disease. We used corticosteroid for the treatment of ulcerative colitis in 60
      year-old woman. Then, Kaposi's sarcoma occurred in the skin and colon of the
      patient. Since she was HIV-negative, we believed that it was developed from the
      condition of corticosteroid-induced immunosuppression. We present a case of skin
      and colonic Kaposi's sarcoma in a HIV-negative woman following treatment with
      corticosteroid for ulcerative colitis.

PMID- 15156121
TI  - [What is the principle of endoscopic removal technique of foreign bodies in the
      upper gastrointestinal tract?].

PMID- 15156120
TI  - [A case of chronic acalculous cholecystitis diagnosed by delayed contrast
      emptying in gallbladder].
AB  - Chronic acalculous cholecystitis is a diagnosis of exclusion in patients
      complaining acalculous biliary pain. The possible causes of acalculous biliary
      pain are chronic gallbladder (GB) inflammation, GB dysfunction, cholesterolosis,
      cystic duct stenosis or microlithiasis. Recently, laparoscopic cholecystectomy is
      the choice of treatment for acalculous biliary pain. We experienced a 32-year-old
      woman whose initial symptoms were right upper quadrant pain and nausea only. The
      abdominal computed tomography, DISIDA scan, and upper and lower endoscopic
      examinations were nonspecific. Up to 48 hours after endoscopic retrograde
      cholangiopancreatography, contrast emptying of GB was delayed, implying
      dysfunctional GB. As the patient's right upper quadrant pain and tenderness
      became aggravated, the laparoscopic cholecystectomy was done and the final
      diagnosis of chronic acalculous cholecystitis was confirmed.

PMID- 15156122
TI  - Vascular disease public education: the mandate is international.

PMID- 15156124
TI  - Hemostatic function and carotid artery disease.
AB  - AIM: Since conventional risk factors predict less than one half of future
      cardiovascular events, other factors that contribute to atherogenesis need to be
      evaluated. The aim of this study was to investigate whether clotting factors are
      associated with carotid artery disease. Furthermore, we tried to determine
      whether clotting factors could be used to predict the risk of cerebrovascular
      events in patients with internal carotid artery stenosis. METHODS: Twenty-six
      patients with high-grade (>70%) internal carotid artery stenosis and 43 age
      matched controls were evaluated for atherogenic risk factors and hemostatic
      function. Laboratory tests included plasma assays of fibrinogen, tissue
      plasminogen activator (TPA), D-dimer, plasminogen activator inhibitor 1 (PAI-1),
      plasminogen and factor VII:c. Nineteen (72%) patients had history of stroke or
      transient ischemic attack, while the remaining 7 (28%) were asymptomatic.
      Statistical analysis was performed using multiple linear regression analysis.
      RESULTS: Carotid artery stenosis was associated with high levels of TPA
      (p<0.001), D-dimer (p=0.019) and PAI-1 (p<0.001). No statistically significant
      correlation was found between the presence of carotid artery disease and the
      levels of fibrinogen (p=0.28), plasminogen (p=0.96) or factor VII:c (p=0.19). As
      regards the clinical manifestations, none of the studied clotting factors was
      correlated with the history of cerebrovascular events in the patients with
      carotid stenosis. CONCLUSION: The results of this study show that the hemostatic
      system may play a role in the development of carotid artery atherosclerotic
      disease, while it does not seem to affect the development of symptoms in patients
      with carotid stenosis.

PMID- 15156125
TI  - Increased soluble E-selectin levels in type 2 diabetic patients with peripheral
      arterial disease.
AB  - AIM: Abnormal endothelial function is well known in patients with type 2 diabetes
      mellitus and thought to induce macroangiopathy. Increased levels of adhesion
      molecules have been found in type 2 diabetic patients and it has been suggested
      that they play an important role in the initiation of atherosclerosis. The aim of
      the present study was to clarify the relationship between objectively proven
      peripheral arterial disease (pAVD) and serum levels of soluble adhesion molecules
      in patients with type 2 diabetes mellitus. METHODS: Levels of soluble E-selectin,
      ICAM-1 and VCAM-1 were evaluated in 18 type 2 diabetic patients with pAVD
      assessed by Doppler ultrasound, in 19 type 2 diabetic patients and 22 non
      diabetic subjects without pAVD. RESULTS: Soluble E-selectin levels were
      significantly increased in pAVD-diabetic patients compared to diabetics and non
      diabetics without pAVD (78.7+/-29 vs 49.7+/-20.4 and 36+/-17 ng/ml respectively,
      p<0.001), while sICAM-1 and sVCAM-1 levels were comparable between the groups. No
      significant correlation was found between pAVD and adhesion molecule levels.
      Peripheral AVD was correlated with smoking (p=0.024), duration of diabetes
      (p=0.048) and microalbuminuria (p=0.041). Regression analysis revealed that only
      smoking (R=0.536, p=0.012) and glycosylated hemoglobin (R=0.435, p=0.036) were
      independent factors related to pAVD. Soluble ICAM-1 levels were significantly
      higher (p=0.041) in diabetic smokers with pAVD and sVCAM-1 (p=0.011) in patients
      with longer duration of diabetes. CONCLUSION: Type 2 diabetic patients with pAVD
      showed increased serum sE-selectin levels. No significant relationship was found
      between the presence or extent of pAVD and measured adhesion molecules. Our
      results suggest that sE-selectin reflects endothelial activation and is possibly
      involved in the atherogenesis process with the contribution of other factors that
      characterize the metabolic syndrome of diabetes.

PMID- 15156126
TI  - Hemodynamics of the sapheno-femoral junction. Patterns of reflux and their
      clinical implications.
AB  - AIM: The detection of reflux elicited by the compression/release test with the PW
      Doppler sample at the level of the sapheno-femoral arch might not be sufficient
      by itself to diagnose the incompetence of the whole sapheno-femoral junction
      (SFJ). The aim of this study was to further refine the diagnosis by positioning
      the PW Doppler sample at different levels of SFJ and eliciting reflux both by
      squeezing and with the Valsalva manoeuvre. In addition, the relationship of the
      findings with the vein diameter was taken into consideration. METHODS: By using a
      high resolution duplex scanner, 1 294 great saphenous veins (GSV) found to be
      incompetent by the compression/release test at duplex investigation of the
      saphenous arch, were also tested at the same level by the Valsalva manoeuvre.
      Subsequently, the tests were repeated by positioning the PW Doppler sample at the
      femoral side of the terminal valve, at the saphenous arch tributaries, and at the
      pre-terminal valve level. Furthermore, the GSV diameter in the standing position
      was measured at 15 cm from the groin in all patients, and correlated with the
      hemodynamic patterns found at the junction level. RESULTS: Comparing to
      compression/release test at the level of the saphenous arch, the Valsalva
      manoeuvre was negative in 259 (20%) lower limbs and positive in 1 035 (80%).
      Among the 1 294 GSV found to be incompetent at compression/release test at the
      level of the saphenous arch, only 710 (55%) lower limbs showed incompetence of
      the terminal valve. A total of 124 patients (10%), presenting with a competent
      terminal valve but with a positive Valsalva manoeuvre in the arch, showed a
      downward flow from a pelvic tributary of the GSV. Finally, a significant
      statistical correlation between the presence of a competent terminal valve and a
      GSV diameter <5 mm has been found (p<0.001). CONCLUSION: Our data show that the
      detection of reflux elicited by compression/release test at the level of the
      saphenous arch is insufficient to diagnose the incompetence of the terminal
      valve. Our results, together with the correlation between the saphenous trunk
      diameter at the thigh and the competence or the incompetence of the terminal
      valve, present significant clinical implications when sapheno-femoral surgical
      disconnection is contemplated.

PMID- 15156127
TI  - Risk factors for varicose veins.
AB  - AIM: To determine the prevalence of varicose veins in the German population and
      specify possible risk factors the data of the Duesseldorf/Essen civil servants
      study were analysed. METHODS: From December 1989 to July 1993 a total of 9 935
      employees were recruited. All volunteers filled out a questionnaire regarding
      family history and risk factors and were clinically examined. Venous findings
      were classified and adapted to the CEAP-classification. For the analysis of risk
      factors only volunteers classified as CEAP-class 0 or as CEAP-class II were
      considered: 4 250 men, 10% belonged to CEAP-class II and 2 380 women including
      16% CEAP-class II. RESULTS: In general, age and gender were the most relevant
      risk factors for varicose veins. Odds ratio age: male: 3.4 (95%-CI: 2.6-4.4), age
      female 6.5 (95%-CI: 5.0-8.5), gender 2.3 (95%-CI 1.9-2.7). In addition in females
      the most frequent risk factors were oral contraception and in both genders a
      predominately sitting posture at work. Regarding the family history, varicose
      veins by the mother was most frequent compared to varicose veins by the father or
      both. After adjusting for age and gender heridity became the most important risk
      factor with an odds ratio of 5.2 (95%-CI:3.7-7.3-4.50) in case of varicose veins
      present in both parents, followed by a standing posture at work 2.2 (95%-CI: 1.2
      3.9). In contrast, smoking also reached a significant level, but with a decreased
      odds ratio of 0.66 (95%-CI: 0.57-0.77) indicating a protective effect.
      CONCLUSION: In addition to age and gender a family history of varicose veins is
      the most important risk factor in the total population. Despite significant
      influence of other risk factors their relevance for varicose veins in the
      investigated population is low either due to low frequencies or low odds ratios.

PMID- 15156128
TI  - Hyperhomocysteinemia: marker of systemic atherosclerosis in peripheral arterial
      disease.
AB  - AIM: Patients suffering from peripheral arterial disease (PAD) are increasingly
      described as having hyperhomocysteinemia more than in patients with coronary
      artery or cerebrovascular disease. Cases of symptomatic PAD usually present with
      associated coronary artery or cerebrovascular disease and renal artery disease.
      It can thus be postulated that multilocular atherosclerosis is linked to
      hyperhomocysteinemia and that the extent of atherosclerosis has a possible
      correlation with homocysteine concentrations. The aim of this study was to
      ascertain whether fasting total homocysteine concentrations in patients with PAD
      are associated with the extent and the localization of systemic atherosclerosis
      in cerebrovascular, coronary and/or renal vascular zones. METHODS: A total of 183
      patients with PAD, Fontaine stages II-IV, were divided into 2 groups: Group A
      contained patients with isolated PAD (n=98) and Group B patients with systemic
      atherosclerosis in PAD (n=85). Characterization of vascular disease in various
      vascular zones was indication-adapted using non-invasive and/or invasive METHODS:
      Patients with renal insufficiency were excluded from the study. RESULTS:
      Homocysteine concentrations were significantly lower in patients with isolated
      PAD than in patients with additional systemic atherosclerosis (10.1+/-4.4 vs
      16.7+/-7.04 micromol/l, p<0.0001). There were no differences in localization or
      extent of concomitant systemic atherosclerosis. Logistic regression analysis
      indicated that elevated plasma homocysteine and decreasing ABPI served
      independently as significant risk indicators for systemic atherosclerosis in
      patients with PAD (p<0.0001). CONCLUSION: Hyperhomocysteinemia is a precursoral
      marker of systemic atherosclerosis and thus a prognostic indicator of
      cardiovascular morbidity and mortality in PAD.

PMID- 15156129
TI  - Carotid and femoral B-mode ultrasound intima-media thickness measurements in
      adult post-coarctectomy patients.
AB  - AIM: Cardiovascular and cerebrovascular morbidity and mortality in adult post
      coarctectomy patients is increased even after successful surgical repair of the
      aorta. B-mode ultrasound intima-media thickness (IMT), a validated marker for
      atherosclerosis and vascular disease risk, was used to measure pre-coarctatial
      carotid and post-coarctatial femoral arterial wall changes in these patients.
      METHODS: Measurements were done in 131 patients (mean age 31.6 y [SD 11.3 y]; 78
      were normotensive, 53 were hypertensive) and in 26 controls (30.9 y [SD 9.4 y]).
      RESULTS: Age, serum lipids and smoking history were similar in patients and
      controls. Overall, IMT in patients and controls were similar (0.59 mm [SD 0.14
      mm] and 0.59 mm [SD 0.08 mm]. In patients, carotid IMT was increased (0.67 mm [SD
      0.12 mm] vs 0.61 mm [SD 0.08 mm] in controls: p=0.01); femoral IMT was decreased
      (0.48 mm [SD 0.09 mm] vs 0.57 mm [SD 0.07 mm]: p=0.001). In normotensive patients
      carotid IMT was not increased (0.64 mm [SD 0.12 mm] vs 0.61 mm [SD 0.08 mm]:
      p=0.2), but patients showed a higher SD. Carotid IMT in hypertensive patients was
      increased (0.72 mm [SD 0.12 mm] vs 0.64 mm [SD 0.11 mm] in normotensive patients:
      p<0.001). The femoral IMT in normo- and hypertensives patients were similar (0.48
      mm [SD 0.09 mm] and 0.49 mm [SD 0.10 mm]: p=0.12). Carotid IMT in patients with
      aortic coarction and age at surgery were associated (r=0.36, p<0.0001), where
      femoral IMT is not. CONCLUSION: Early peripheral arterial wall damage is
      prominent in hypertensive post-coarctatial patients and is limited to pre
      coarctatial conduits. The decreased femoral IMT in all patients may indicate a
      relatively low post-coarctatial blood pressure if pressure control is guided
      according to pre-coarctatial RR. Pre-coarctatial arterial wall change is less
      apparent in post-coarctectomy patients who have a controlled blood pressure and
      who had early surgical repair.

PMID- 15156130
TI  - Ruptured abdominal aortic aneurysm. Is it possible to predict outcome?
AB  - AIM: Mortality after ruptured abdominal aortic aneurysm (rAAA) remains high.
      Hardman et al. suggested that the following factors predict perioperative death:
      age >76 years, loss of consciousness, ECG confirmed ischemia, creatinine over 180
      micromol/l and hemoglobin below 9 g/dl. A score of 3 or more had 100% mortality.
      A retrospective study was performed to validate this and determine if
      modification is required. METHODS: Retrospective analysis of the 5 Hardman Index
      factors along with preoperative systolic blood pressure at presentation, after
      resuscitation and during surgery was performed. RESULTS: A total of 137 cases
      were reviewed with overall mortality of 56.2%. Of Hardman's criteria: age, ECG
      ischemic changes, creatinine and hemoglobin levels were significant in predicting
      outcome (p=0.0007, 0.0152, 0.0001 and 0.0213, respectively). Loss of
      consciousness was not significant (p=0.9054). Hardman scores of 0, 1, 2, 3, and 4
      scored mortality percentages of 40.4%, 46.4%, 76.7%, 91.7% and 100%,
      respectively. Systolic blood pressure was significantly predictive at 100 mmHg
      and 120 mmHg on presentation (p=0.0008 and 0.0017, respectively) and 100 mmHg and
      120 mmHg after resuscitation (p=0.0001 and 0.0510, respectively). A modified
      score replaced loss of consciousness with systolic blood pressure below 100 mmHg
      with scores of 0, 1, 2, 3, and 4 had mortality of 22.2%, 46.8%, 66.7%, 83.9% and
      100%, respectively. CONCLUSION: Our data supports the effectiveness of the
      Hardman Index in predicting successful surgery. However loss of consciousness was
      not a significant predictor. We proposed review of predictive indices, but
      resources should be channelled into screening to prevent rAAA.

PMID- 15156132
TI  - A comparison of physiology scores and morphology in a group of patients evaluated
      for endovascular repair of infrarenal aneurysms.
AB  - AIM: Endovascular repair (EVR) of abdominal aortic aneurysms (AAA) is an accepted
      alternative to open repair (OR). Anatomical suitability for EVR of 196
      consecutive AAA referrals is analysed, according to aneurysm size and relative
      physiological fitness for OR. METHODS: Patients were evaluated for suitability
      according to 2 sets of arbitrary EVR anatomical criteria: flexible criteria (FC),
      and a subgroup, rigid criteria (RC) with few technical risks. Suitability was
      related to aneurysm size and operative risk (POSSUM). RESULTS: Eighty-eight
      patients (45%) were suitable by FC, 33 (17%) by RC, and 108 (55%) were unsuitable
      for EVR. Inadequate neck length (56%) and angulation (26%), were principle
      reasons for unsuitability. Mean AAA diameter was 60.5 mm for the whole group,
      58.4 mm for those suitable by FC, 56.5 mm for those suitable by RC and 62.1 mm in
      those unsuitable (p<0.01). Median physiology scores (interquartile ranges) were
      19 (17-21) overall, 18 (17-21) in those suitable FC, 18 (17-19) in those suitable
      by RC and 19 (18-21) for unsuitable patients (NS). High risk patients with large
      aneurysms. There were 133 larger aneurysms (=/>55 mm in diameter), of which there
      were 56 patients with physiology scores =/>20. Of these 16 (29%) and 4 (7%) were
      suitable by FC and RC, respectively. By comparison, of the remaining 77 with
      physiology scores of =/<19.35 (45%) were suitable for FC and 15 (19%) for RC
      (p<0.05). CONCLUSION: Unfit patients with significantly sized aneurysm;
      ironically those most likely to benefit, tend to be less suitable for EVR.

PMID- 15156131
TI  - Popliteal artery aneurysms. Factors associated with thromboembolism and graft
      failure.
AB  - AIM: The purpose of this study was to review our experience with popliteal artery
      aneurysms (PAAS) and to identify the major factors associated with
      thromboembolism of PAAS and failure of grafts after surgical repair. METHODS: The
      medical records of 38 patients with 42 PAA, who presented in a university medical
      center between March 1985 and September 2000, were retrospectively reviewed. Data
      were collected on clinical presentation, risk factors, type of reconstructions,
      early and late morbidity, limb loss and mortality. Duplex scan, as well as
      computed tomography, was performed in 33 (78.6%) cases, and preoperative
      angiography in 38 (90.5%). Thrombolysis was performed prior to surgical
      reconstruction (16.07+/-21.97 months) in 4 cases presented with acute ischemia.
      All patients underwent synthetic (23, 54.8%) or autogenous (19, 45.2%), below-the
      knee (39, 92.9%) or above-the-knee (3, 7.1%) femoropopliteal bypass graft. The
      proximal and distal anastomoses were end-to-end both in both cases in 30 bypasses
      (71.4%). Thirty-six (86%) aneurysms were surgically treated by one vascular
      surgeon. Postoperative anticoagulants were given in 8 cases (19%). Long-term
      follow-up (mean: 57.59+/-37.77 months) was available for 35 patients (92.1%).
      Multivariate analysis was used to assess association between risk factors and
      outcome. RESULTS: Thirty-five patients were males, 3 were females; mean age was
      68.31+/-8.66 years. Risk factors were arterial hypertension (25, 69%), smoking
      (19, 50%), dyslipidemia (7, 18.4%) and diabetes (5, 13.2%). Thirty PAAS (71.4%)
      were symptomatic for acute (11, 26.2%) or chronic (7, 16.7%) ischemia, distal
      embolization (8, 19%), compression of the popliteal fossa (3, 7.1%) and rupture
      (2, 4.8%, one of which presented with acute ischemia); 12 were asymptomatic.
      Bilateral PAAS were present in 18 patients (47.4%); 14 (36.8%) also had an
      abdominal aortic aneurysm (AAA); associated AAAS were twice as common in patients
      with bilateral PAAS (9/18, 50%) compared to those with unilateral PAAS (5/20,
      25%; p=NS). The mean diameter of the PAAS was 3.4 cm; no significant difference
      was found in the mean diameter of symptomatic and asymptomatic aneurysms.
      Complete thrombosis of the aneurysmal sac was found in 15 cases (35.7%), severe
      atherosclerotic femoro-popliteal lesions in 17 (40.5%), arteriomegaly in 11
      (26.2%), occlusion of the superficial femoral artery (SFA) in 7 (16.7%). Three
      leg arteries were present in 17 limbs (40.5%), 2 in 6 (14.3%), 1 in 7 (16.7%), no
      leg vessels in 12 (28.6%). Occlusion of the SFA and the absence of major leg
      arteries were independently associated with thrombosis of the aneurysmal sac
      (p=0.005). Two-thirds of patients with thrombosed PAA (10, 66.7%) presented with
      acute ischemia, while 1/3 (5, 33.3%; p=NS) had some degree of claudication.
      Optimal runoff (score=1) was estimated in 23 limbs, while score was between 2-7
      in 19 limbs. Thrombolysis was successful in all 4 cases, with no complications.
      Primary graft patency was 66.1% at 4 years; the only variables independently
      associated with loss of bypass patency were smoking (p=0.04) and poor leg runoff
      (p=0.02). Postoperative bypass occlusion occurred in 2 cases presented
      respectively with acute and chronic ischemia, and in 2 asymptomatic patients; all
      4 bypasses were polytetrafluoroethylene grafts. A total of 8 thrombosed,
      polytetrafluoroethylene, below-the-knee bypass grafts required secondary
      reconstructions (2 redo + 6 restorative procedures). The secondary patency rate
      at 3 years was 77.9%. Lower limb amputation had to be performed 2 months after
      primary reconstruction in 1 case (2.4%) presented with acute ischemia. The
      estimated limb salvage rate at 10 years was 96%. Mortality was 4.8%. Survival at
      6 years was 82.6%. CONCLUSION: Our experience indicates that SFA occlusion and
      poor runoff vessels were independent factors associated with PAA thrombosis. The
      diameter of asymptomatic PAAs was not significantly different than that of
      asymptomatic ones. Use of tobacco and poor runoff vessels were independent
      factors associated with primary bypass patency. In PAAs complicated with acute
      ischemia, thrombolysis allowed us to regain a good runoff and to perform
      subsequent bypass procedure, with no amputation. The use of autogenous graft
      material, when possible, is recommended.

PMID- 15156134
TI  - Vascular surgery training in Greece.
AB  - The aim of the study was to describe current training in vascular surgery in
      Greece. The method used was the presentation of data obtained by direct contact
      with the units. Vascular surgery has been a mono-specialty in Greece since 1989.
      The duration of training is 7 years (3 years common trunk in general surgery, 3
      years in vascular surgery and 1 year in cardiothoracic surgery). However, its
      duration often exceeds 11 years due to lost time in waiting to start training.
      The latter happens because there has been a tremendous increase of the number of
      medical graduates during the last decade and thus the number of trainees has
      increased disproportionately to the demand for vascular surgeons nationwide.
      Greece has the second higher ratio of vascular trainees per million population in
      EU (3.6 trainees/million population). There are 14 accredited centres for
      training in vascular surgery, the majority of them being in Athens (9/14). In
      these centres there are a total of 52 trainers and 38 trainees (ratio 1.4/1). An
      average of 380 operations are performed per centre/year and 140
      operations/trainee/year. In conclusion, there is a need for re-defining the
      training programme in vascular surgery in Greece. The main concern is the
      tremendous increase in medical graduates leading to a discrepancy between
      accredited training posts and fellows waiting to fill them.

PMID- 15156133
TI  - The evaluation of the no-independent vasodilatative effect of iloprost in
      isolated perfused Guinea pig hind limbs.
AB  - AIM: In critical limb ischemia vasodilatators play an important role in the
      treatment of the disease. Considering that the endothelium is seriously damaged
      in these patients, we wanted to evaluate if the vasodilatative effect of iloprost
      does or does not depend on the endothelium by using the model of the isolated
      perfused guinea pig hind limb. METHODS: A catheter was inserted via the distal
      aorta and common iliac artery. After stabilization, iloprost was administered at
      a dosage of 0.1 microM. In a subsequent series of experiments precontraction of
      the peripheral vascular bed was achieved with 40 mM KCl followed by 0.1 microM
      iloprost. In a 3rd series of experiments L-NAME (100 microM) was administered
      after the equilibration period for 30 minutes, followed by 0.1 microM iloprost.
      In the 4th series of experiments, after the administration of L-NAME (100
      microM), KCl (40 mM) was administered to precontract the vascular bed and
      iloprost 0.1 microM was added. RESULTS: The administration of iloprost alone and
      after addition of KCL induced a significant decrease in vascular resistance(
      49.6+/-14.1% [x+/-SEM, n=7]). The addition of L-NAME did not affect vascular
      resistance. The consecutive addition of iloprost reduced vascular resistance
      significantly (-4.2+/-0.7% [x+/-SEM, n=7]). After addition of L-NAME 100 microM
      and precontraction with KCl 40 mM, iloprost once again significantly reduced
      peripheral vascular resistance (-51.5+/-14.4% [x+/-SEM, n=6]). Reduction of
      peripheral vascular resistance by iloprost was comparable to that without L-NAME.
      CONCLUSION: Our data show that iloprost at a dosage of 0.1 microM achieves a
      significant reduction in peripheral vascular resistance and that the
      vasodilatative effect of iloprost is independent of NO. Iloprost therefore seems
      to be an ideal vasodilatative drug for the treatment of patients with impaired
      endothelial function.

PMID- 15156135
TI  - Glomangioma of the upper limb associated with hypoplastic-dysplastic superficial
      venous system.
AB  - The diagnosis and therapy of vascular malformations is difficult. An important
      factor, which influences the therapeutic approach, is the complicated vascular
      network of the lesions. The frequent involvement of various structures (muscles,
      bones or other organs) makes the surgical intervention arduous. Glomus tumors are
      rare, symptomatic (painful) lesions, with dimensions ranging 3-10 mm and usually
      subungual location, which need radical resection as a therapy. The case we
      present is the first one where a glomus tumor presents as a hypoplastic
      dysplastic superficial venous system, located parallel to the normal superficial
      venous system of the left upper extremity, resembling a form of varicosities. The
      atypical clinical presentation and the unique morphology classify this case in a
      very limited category of nosological entities.

PMID- 15156136
TI  - Tumor embolization causing acute ischemia with sometimes fatal results. Case
      report and review of literature.
AB  - Peripheral arterial embolism arising from a malignant tumor is an infrequent
      manifestation of neoplastic disease and also a rare cause of acute arterial
      occlusion. A diagnosis of lower limb acute ischemia in young adults could be
      overlooked because the condition is quite uncommon in this age group. A case of
      lower extremities arterial embolization from metastatic lung cancer of germ cell
      origin is reported and the literature is reviewed.

PMID- 15156137
TI  - Tuberculous pseudoaneurysm of the celiac artery. A case report.
AB  - We report a case of tuberculous pseudoaneurysm in the neck of the celiac artery
      involving the aorta. Recurrence of the aneurysm occurred after attempted direct
      repair. Therefore redo-surgery was performed, which involved resection of
      aneurysm and removal of the infected tissue with bilateral axillofemoral bypass.

PMID- 15156138
TI  - MR angiography of the anomalous branching of aortic arch and left subclavian
      artery arising from Kommerell's diverticulum. Case report.
AB  - We report the magnetic resonance (MR) angiographic findings of an asymptomatic
      case with abnormal branching of aortic arch and Kommerell's diverticulum, which
      to our knowledge has not been described previously.

PMID- 15156139
TI  - Receptor editing is the main mechanism of B cell tolerance toward membrane
      antigens.
AB  - Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are
      eliminated in the bone marrow by two mechanisms of tolerance: receptor editing
      and clonal deletion. However, the relative contributions of clonal deletion and
      receptor editing to B cell tolerance in a polyclonal B cell population have not
      been established. Here we show that tolerance toward a membrane antigen-reactive
      B cell clone acts by receptor editing with very minimal cell loss. The capacity
      of receptor editing to rescue almost all autoreactive B cells from deletion
      relies on the availability of multiple joining light chain gene segments as
      substrate for secondary immunoglobulin light chain gene rearrangement and is
      independent of the affinity of the autoantigen and the presence of non
      autoreactive B cells. Our data further suggest that clonal deletion is a default
      pathway that functions only when receptor editing has been exhausted.

PMID- 15156140
TI  - 'Educated' dendritic cells act as messengers from memory to naive T helper cells.
AB  - Ingested antigens lead to the generation of effector T cells that secrete
      interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of
      influencing naive T cells in their immediate environment to do the same. Using
      chimeric mice generated by aggregation of two genotypically different embryos, we
      found that the conversion of a naive T cell occurs only if it can interact with
      the same antigen-presenting cell, although not necessarily the same antigen, as
      the effector T cell. Using a two-step culture system in vitro, we found that
      antigen-presenting dendritic cells can act as 'temporal bridges' to relay
      information from orally immunized memory CD4 T cells to naive CD4 T cells. The
      orally immunized T cells use IL-4 and IL-10 (but not CD40 ligand) to 'educate'
      dendritic cells, which in turn induce naive T cells to produce the same cytokines
      as those produced by the orally immunized memory T cells.

PMID- 15156141
TI  - CpG island hypermethylation is maintained in human colorectal cancer cells after
      RNAi-mediated depletion of DNMT1.
AB  - The role of the primary mammalian DNA methyltransferase, DNMT1, in maintaining
      CpG island methylation in human colon cancer cells has recently been questioned.
      This controversy has arisen from discrepancies between genetic knockout and RNA
      interference-mediated knockdown studies. Here, we re-examined the RNA
      interference-based approach and found that hypermethylation of single-copy genes
      is maintained in cells transiently and stably depleted of DNMT1.

PMID- 15156142
TI  - Plzf is required in adult male germ cells for stem cell self-renewal.
AB  - Adult germline stem cells are capable of self-renewal, tissue regeneration and
      production of large numbers of differentiated progeny. We show here that the
      classical mouse mutant luxoid affects adult germline stem cell self-renewal.
      Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa
      and then progressively lose their germ line after birth. Transplantation studies
      showed that germ cells from mutant mice did not colonize recipient testes,
      suggesting that the defect is intrinsic to the stem cells. We determined that the
      luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a
      transcriptional repressor that regulates the epigenetic state of undifferentiated
      cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated
      spermatogonia. This is the first gene shown to be required in germ cells for stem
      cell self-renewal in mammals.

PMID- 15156143
TI  - Essential role of Plzf in maintenance of spermatogonial stem cells.
AB  - Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ
      cells of the testis, self-renew and differentiate into sperm. Here we show that
      Zfp145, encoding the transcriptional repressor Plzf, has a crucial role in
      spermatogenesis. Zfp145 expression was restricted to gonocytes and
      undifferentiated spermatogonia and was absent in tubules of W/W(v) mutants that
      lack these cells. Mice lacking Zfp145 underwent a progressive loss of
      spermatogonia with age, associated with increases in apoptosis and subsequent
      loss of tubule structure but without overt differentiation defects or loss of the
      supporting Sertoli cells. Spermatogonial transplantation experiments revealed a
      depletion of spermatogonial stem cells in the adult. Microarray analysis of
      isolated spermatogonia from Zfp145-null mice before testis degeneration showed
      alterations in the expression profile of genes associated with spermatogenesis.
      These results identify Plzf as a spermatogonia-specific transcription factor in
      the testis that is required to regulate self-renewal and maintenance of the stem
      cell pool.

PMID- 15156144
TI  - The mouse X chromosome is enriched for sex-biased genes not subject to selection
      by meiotic sex chromosome inactivation.
AB  - Sex chromosomes are subject to sex-specific selective evolutionary forces. One
      model predicts that genes with sex-biased expression should be enriched on the X
      chromosome. In agreement with Rice's hypothesis, spermatogonial genes are over
      represented on the X chromosome of mice and sex- and reproduction-related genes
      are over-represented on the human X chromosome. Male-biased genes are under
      represented on the X chromosome in worms and flies, however. Here we show that
      mouse spermatogenesis genes are relatively under-represented on the X chromosome
      and female-biased genes are enriched on it. We used Spo11(-/-) mice blocked in
      spermatogenesis early in meiosis to evaluate the temporal pattern of gene
      expression in sperm development. Genes expressed before the Spo11 block are
      enriched on the X chromosome, whereas those expressed later in spermatogenesis
      are depleted. Inactivation of the X chromosome in male meiosis may be a universal
      driving force for X-chromosome demasculinization.

PMID- 15156145
TI  - Astrocytes contain a vesicular compartment that is competent for regulated
      exocytosis of glutamate.
AB  - Astrocytes establish rapid cell-to-cell communication through the release of
      chemical transmitters. The underlying mechanisms and functional significance of
      this release are, however, not well understood. Here we identify an astrocytic
      vesicular compartment that is competent for glutamate exocytosis. Using
      postembedding immunogold labeling of the rat hippocampus, we show that vesicular
      glutamate transporters (VGLUT1/2) and the vesicular SNARE protein, cellubrevin,
      are both expressed in small vesicular organelles that resemble synaptic vesicles
      of glutamatergic terminals. Astrocytic vesicles, which are not as densely packed
      as their neuronal counterparts, can be observed in small groups at sites adjacent
      to neuronal structures bearing glutamate receptors. Fluorescently tagged VGLUT
      containing vesicles were studied dynamically in living astrocytes by total
      internal reflection fluorescence (TIRF) microscopy. After activation of
      metabotropic glutamate receptors, astrocytic vesicles underwent rapid
      (milliseconds) Ca(2+)- and SNARE-dependent exocytic fusion that was accompanied
      by glutamate release. These data document the existence of a Ca(2+)-dependent
      quantal glutamate release activity in glia that was previously considered to be
      specific to synapses.

PMID- 15156146
TI  - A sensory signature that distinguishes true from false memories.
AB  - Human behavioral studies show that there is greater sensory/perceptual detail
      associated with true memories than false memories. We therefore hypothesized that
      true recognition of abstract shapes would elicit greater visual cortical
      activation than would false recognition. During functional magnetic resonance
      imaging (fMRI), participants studied exemplar shapes and later made recognition
      memory decisions ("old" or "new") concerning studied exemplars (old shapes),
      nonstudied lures (related shapes) and new shapes. Within visual processing
      regions, direct contrasts between true recognition ("old" response to an old
      shape; old-hit) and false recognition ("old" response to a related shape; related
      false alarm) revealed preferential true recognition-related activity in early
      visual processing regions (Brodmann area (BA)17, BA18). By comparison, both true
      and false recognition were associated with activity in early and late (BA19,
      BA37) visual processing regions, the late regions potentially supporting "old"
      responses, independent of accuracy. Further analyses suggested that the
      differential early visual processing activity reflected repetition priming, a
      type of implicit memory. Thus, the sensory signature that distinguishes true from
      false recognition may not be accessible to conscious awareness.

PMID- 15156147
TI  - Computational subunits in thin dendrites of pyramidal cells.
AB  - The thin basal and oblique dendrites of cortical pyramidal neurons receive most
      of the synaptic inputs from other cells, but their integrative properties remain
      uncertain. Previous studies have most often reported global linear or sublinear
      summation. An alternative view, supported by biophysical modeling studies, holds
      that thin dendrites provide a layer of independent computational 'subunits' that
      sigmoidally modulate their inputs prior to global summation. To distinguish these
      possibilities, we combined confocal imaging and dual-site focal synaptic
      stimulation of identified thin dendrites in rat neocortical pyramidal neurons. We
      found that nearby inputs on the same branch summed sigmoidally, whereas widely
      separated inputs or inputs to different branches summed linearly. This strong
      spatial compartmentalization effect is incompatible with a global summation rule
      and provides the first experimental support for a two-layer 'neural network'
      model of pyramidal neuron thin-branch integration. Our findings could have
      important implications for the computing and memory-related functions of cortical
      tissue.

PMID- 15156148
TI  - Induction of PGE2 by estradiol mediates developmental masculinization of sex
      behavior.
AB  - Adult male sexual behavior in mammals requires the neuronal organizing effects of
      gonadal steroids during a sensitive perinatal period. During development,
      estradiol differentiates the rat preoptic area (POA), an essential brain region
      in the male copulatory circuit. Here we report that increases in prostaglandin
      E(2) (PGE(2)), resulting from changes in cyclooxygenase-2 (COX-2) regulation
      induced by perinatal exposure to estradiol, are necessary and sufficient to
      organize the crucial neural substrate that mediates male sexual behavior. Briefly
      preventing prostaglandin synthesis in newborn males with the COX inhibitor
      indomethacin permanently downregulates markers of dendritic spines in the POA and
      severely impairs male sexual behavior. Developmental exposure to the COX
      inhibitor aspirin results in mild impairment of sexual behavior. Conversely,
      administration of PGE(2) to newborn females masculinizes the POA and leads to
      male sex behavior in adults, thereby highlighting the pathway of steroid
      independent brain masculinization. Our findings show that PGE(2) functions as a
      downstream effector of estradiol to permanently masculinize the brain.

PMID- 15156149
TI  - Perceptual learning and top-down influences in primary visual cortex.
AB  - Neuronal responses at early stages in visual cortical processing, including those
      in primary visual cortex (V1), are subject to the influences of visual context,
      experience and attention. Here we show that for monkeys trained in a shape
      discrimination task, V1 neurons took on novel functional properties related to
      the attributes of the trained shapes. Furthermore, these properties depended on
      the perceptual task being performed; neurons responded very differently to an
      identical visual stimulus under different visual discrimination tasks. These top
      down influences were seen from the very beginning and throughout the entire time
      course of the neural responses. Information theoretic analysis showed that
      neurons carried more information about a stimulus attribute when the animals were
      performing a task related to that attribute. Our findings suggest that the output
      from V1 reflects both sensory and behavioral context.

PMID- 15156150
TI  - Attentional modulation of human auditory cortex.
AB  - Attention powerfully influences auditory perception, but little is understood
      about the mechanisms whereby attention sharpens responses to unattended sounds.
      We used high-resolution surface mapping techniques (using functional magnetic
      resonance imaging, fMRI) to examine activity in human auditory cortex during an
      intermodal selective attention task. Stimulus-dependent activations (SDAs),
      evoked by unattended sounds during demanding visual tasks, were maximal over
      mesial auditory cortex. They were tuned to sound frequency and location, and
      showed rapid adaptation to repeated sounds. Attention-related modulations (ARMs)
      were isolated as response enhancements that occurred when subjects performed
      pitch-discrimination tasks. In contrast to SDAs, ARMs were localized to lateral
      auditory cortex, showed broad frequency and location tuning, and increased in
      amplitude with sound repetition. The results suggest a functional dichotomy of
      auditory cortical fields: stimulus-determined mesial fields that faithfully
      transmit acoustic information, and attentionally labile lateral fields that
      analyze acoustic features of behaviorally relevant sounds.

PMID- 15156151
TI  - Memo mediates ErbB2-driven cell motility.
AB  - Clinical studies have revealed that cancer patients whose tumours have increased
      ErbB2 expression tend to have more aggressive, metastatic disease, which is
      associated with parameters predicting a poor outcome. The molecular basis
      underlying ErbB2-dependent cell motility and metastases formation, however, still
      remains poorly understood. In this study, we show that activation of a set of
      signalling molecules, including MAPK, phosphatidylinositol-3-OH kinase (PI(3)K)
      and Src, is required for Neu/ErbB2-dependent lamellipodia formation and for
      motility of breast carcinoma cells. Stimulation of these molecules, however,
      failed to induce efficient cell migration in the absence of Neu/ErbB2
      phosphorylation at Tyr 1201 or Tyr 1227. We describe a novel molecule, Memo
      (mediator of ErbB2-driven cell motility), that interacts with a phospho-Tyr 1227
      containing peptide, most probably through the Shc adaptor protein. After
      Neu/ErbB2 activation, Memo-defective cells form actin fibres and grow
      lamellipodia, but fail to extend microtubules towards the cell cortex. Our data
      suggest that Memo controls cell migration by relaying extracellular chemotactic
      signals to the microtubule cytoskeleton.

PMID- 15156152
TI  - Myosin-X provides a motor-based link between integrins and the cytoskeleton.
AB  - Unconventional myosins are actin-based motors with a growing number of attributed
      functions. Interestingly, it has been proposed that integrins are transported by
      unidentified myosins to facilitate cellular remodelling. Here we present an
      interaction between the unconventional myosin-X (Myo10) FERM (band
      4.1/ezrin/radixin/moesin) domain and an NPXY motif within beta-integrin
      cytoplasmic domains. Importantly, knock-down of Myo10 by short interfering RNA
      impaired integrin function in cell adhesion, whereas overexpression of Myo10
      stimulated the formation and elongation of filopodia in an integrin-dependent
      manner and relocalized integrins together with Myo10 to the tips of filopodia.
      This integrin relocalization and filopodia elongation did not occur with Myo10
      mutants deficient in integrin binding or with a beta(1)-integrin point mutant
      deficient in Myo10 binding. Taken together, these results indicate that Myo10
      mediated relocalization of integrins might serve to form adhesive structures and
      thereby promote filopodial extension.

PMID- 15156153
TI  - Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
AB  - Although the Notch and JAK-STAT signalling pathways fulfill overlapping roles in
      growth and differentiation regulation, no coordination mechanism has been
      proposed to explain their relationship. Here we show that STAT3 is activated in
      the presence of active Notch, as well as the Notch effectors Hes1 and Hes5. Hes
      proteins associate with JAK2 and STAT3, and facilitate complex formation between
      JAK2 and STAT3, thus promoting STAT3 phosphorylation and activation. Furthermore,
      suppression of endogenous Hes1 expression reduces growth factor induction of
      STAT3 phosphorylation. STAT3 seems to be essential for maintenance of radial
      glial cells and differentiation of astrocytes by Notch in the developing central
      nervous system. These results suggest that direct protein-protein interactions
      coordinate cross-talk between the Notch-Hes and JAK-STAT pathways.

PMID- 15156154
TI  - Generic expansion of the substrate spectrum of a DNA polymerase by directed
      evolution.
AB  - DNA polymerases recognize their substrates with exceptionally high specificity,
      restricting the use of unnatural nucleotides and the applications they enable. We
      describe a strategy to expand the substrate range of polymerases. By selecting
      for the extension of distorting 3' mismatches, we obtained mutants of Taq DNA
      polymerase that not only promiscuously extended mismatches, but had acquired a
      generic ability to process a diverse range of noncanonical substrates while
      maintaining high catalytic turnover, processivity and fidelity. Unlike the wild
      type enzyme, they bypassed blocking lesions such as an abasic site, a thymidine
      dimer or the base analog 5-nitroindol and performed PCR amplification with
      complete substitution of all four nucleotide triphosphates with phosphorothioates
      or the substitution of one with the equivalent fluorescent dye-labeled nucleotide
      triphosphate. Such 'unfussy' polymerases have immediate utility, as we
      demonstrate by the generation of microarray probes with up to 20-fold brighter
      fluorescence.

PMID- 15156155
TI  - Serial bull cloning by somatic cell nuclear transfer.
AB  - Although the list of species successfully cloned continues to grow, serial
      cloning has not been reported in species other than the mouse. Here we describe
      two live births of second-generation clones of a bull. Clones of the first and
      second generations appear healthy and have normal telomere lengths. Our attempts
      to produce the third generation of clones were unsuccessful.

PMID- 15156157
TI  - Predicting survival for myeloid leukemia after HLA-identical sibling donor
      allogeneic stem cell transplantation.

PMID- 15156158
TI  - IGF-I induces DNA synthesis and apoptosis in rat liver hepatic stellate cells
      (HSC) but DNA synthesis and proliferation in rat liver myofibroblasts (rMF).
AB  - Several lines of evidence suggest a role of insulin-like growth factor I (IGF-I)
      in the regulation of apoptosis. Up to now its impact on many specific cells is
      unknown. We therefore studied the effect of IGF-I on two similar mesenchymal
      matrix-producing cell types of the liver, the hepatic stellate cells (HSC) and
      the myofibroblasts (rMF). The present study aimed to reveal the influence of IGF
      I on cell cycle and apoptosis of HSC and rMF and to elucidate responsible
      signaling. While IGF-I significantly increased DNA synthesis in HSC, cell number
      decreased and apoptosis increased. In rMF IGF-I also increased DNA synthesis,
      which is, however, followed by proliferation. Blocking extracellular signal
      regulating kinase (ERK) revealed that in HSC, bcl-2 upregulation and bax
      downregulation are effected downstream of ERK, whereas downregulation of NFkappaB
      and consecutive of bcl-xL is mediated upstream. In the rMF upregulation of both,
      the antiapoptotic bcl-2 and bcl-xL is mediated upstream of ERK. The expression of
      the proapoptotic bax is not regulated by IGF-I in rMF. The studies demonstrate a
      completely different effect and signaling of IGF-I in two morphologically and
      functionally similar matrix-producing cells of the liver.

PMID- 15156159
TI  - Promoter hypermethylation silences cyclooxygenase-2 (Cox-2) and regulates growth
      of human hepatocellular carcinoma cells.
AB  - Cyclooxygenase-2 (COX-2) upregulation is recognized to confer advantage in
      progression in a wide variety of cancers, with colorectal cancer most intensively
      investigated. Epidemiologically, chemopreventive effects of COX-2 inhibitors have
      been proven on numerous cancers, but not on hepatocellular carcinoma (HCC).
      Although the antiapoptotic feature of COX-2 generally supports cancer cell
      growth, previous reports have shown that COX-2 expression, upregulated in early
      HCC, is downregulated in advanced HCC. Therefore, COX-2 downregulation may be
      somehow advantageous and specific for HCC development. However, its mechanism
      remains unclear. Since promoter hypermethylation often silences the gene
      expression, we hypothesized that the epigenetic mechanism might regulate COX-2
      expression in HCC. We examined the methylation status of the Cox-2 promoter in
      six human HCC cell lines (Hep3B, HepG2, SK-Hep1, HuH7, PLC, and FLC-7 cells)
      using methylation-specific PCR. The promoter was remarkably hypermethylated in
      Hep3B and FLC-7 cells and moderately in HepG2 and SK-Hep1 cells, but not in HuH7
      and PLC cells. In Hep3B cells, coincubation with 5-aza-2'-deoxycytidine, a
      demethylator, demethylated the promoter and upregulated COX-2 expression as well
      as prostaglandin E2 production dose dependently. On the other hand, no such
      effects were observed in HuH7 cells. Additionally, the methylator suppressed
      growth of Hep3B cells dose dependently, accompanied by cyclin D1 downregulation,
      and the growth suppression was abrogated by potent COX-2 inhibition with a COX-2
      selective inhibitor celecoxib, but these responses were not found in HuH7 cells.
      These results indicated that cell growth was largely retarded by Cox-2
      upregulation via promoter demethylation, rather than the potentially reactivated
      genes concurrently demethylated by 5-aza-2'-deoxycytidine. In conclusion,
      promoter hypermethylation transcriptionally silences Cox-2 in HCC cells.
      Epigenetic alteration of Cox-2, at least in part, modulates the growth of HCC
      cells.

PMID- 15156160
TI  - Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative
      disease.
AB  - The hepatocyte growth factor (HGF) has been crucially implicated in the
      development of proliferative retinal diseases; however, it is unclear whether
      retinal glial cells express or respond to HGF. Therefore, we examined the
      expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical
      costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of
      patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic
      retinopathy (PDR), respectively. Furthermore, it was determined whether cells of
      the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF
      stimulates proliferation and chemotaxis, and secretion of the vascular
      endothelial growth factor (VEGF). Neuroretinas of patients with PVR express
      elevated mRNA level for HGF in comparison to control retinas. In epiretinal
      membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met,
      respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine
      serum and basic fibroblast growth factor, but not heparin-binding epidermal or
      platelet-derived growth factors, evoked HGF secretion by cultured retinal glial
      cells. HGF displayed only a marginal effect on cell proliferation while it
      stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the
      phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal
      membranes express both HGF protein and c-Met receptors. The results suggest an
      autocrine/paracrine role of HGF in glial cell responses during proliferative
      vitreoretinal disorders as well as in retinal neovascularization, by stimulating
      of VEGF release.

PMID- 15156161
TI  - Allogeneic myeloablative transplantation for patients aged 50 years and over.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) has been performed
      mainly for young patients due to concern about the high incidence of treatment
      related mortality (TRM). Recent advances to reduce TRM by using peripheral blood
      stem cells or nonmyeloablative conditioning regimens have increased the age limit
      for this procedure, and correctly identifying the indication for transplant is
      essential for older patients. In this study, we analyzed data from 398 patients
      aged 50 or over selected from 5147 patients, who received conventional allogeneic
      HSCT (c-HSCT). Patients aged 50 or older showed inferior outcomes for TRM and
      overall survival (OS). Mulitivariate analyses confirmed that an age of 50 or over
      was an independent risk factor for TRM (P<0.0001) and OS (P<0.0001). Among
      patients aged 50 or older, increasing age remained an adverse factor for OS
      (P=0.0213). Regimens including total-body irradiation (TBI) correlated with a
      higher risk of TRM and a lower OS for older patients (P=0.0095 and 0.0303,
      respectively). These findings indicate that allogeneic c-HSCT should be offered
      to patients over 50 years only if the increased risk of TRM is acceptable, and
      that a non-TBI regimen is preferable when the transplant is performed.

PMID- 15156162
TI  - Liver graft-versus-host disease after donor lymphocyte infusion for relapses of
      hematologic malignancies post allogeneic hematopoietic stem cell transplantation.
AB  - Graft-versus-host disease (GVHD) is the commonest complication after donor
      lymphocyte infusion (DLI). In 19 patients undergoing DLI for relapses of
      hematologic malignancies post hematopoietic stem cell transplantation (HSCT), 11
      developed GVHD, of whom nine had isolated liver involvement, and two had liver
      and skin involvement. The clinical diagnosis of liver GVHD was hepatitic in six
      patients (55%) and classical in five patients (45%). Patients with GVHD post-DLI
      showed a different clinical pattern when compared to a cohort of 106 cases of
      GVHD post-HSCT, in having significantly more isolated liver involvement (9/11 vs
      17/106, P<0.001), and less skin (2/11 vs 80/106, P<0.001) and gut (0/11 vs
      28/106, P<0.001) involvement. However, liver GVHD post-DLI and post-HSCT had
      comparable patient characteristics, underlying diseases, clinical subtypes
      (classical and hepatitic) and response to treatment.

PMID- 15156163
TI  - Significance of chimerism in hematopoietic stem cell transplantation: new
      variations on an old theme.
AB  - The main goal of post-transplantation monitoring in hematopoietic stem cell
      transplantation (HSCT) is to predict negative events, such as disease relapse,
      graft rejection and graft-versus-host disease, in order to intervene with
      appropriate therapy. In this context, chimerism analysis is an important method
      in monitoring post HSCT outcome. Mixed chimerism (MC) is mainly evaluated to
      define engraftment and relapse. Detection of MC is a prerequisite in both
      myeloablative and nonmyeloablative HSCT, in order to assess the graft status and
      decide later therapeutic strategies such as donor lymphocyte infusion. In this
      review, we discuss various techniques including erythrocyte phenotyping,
      cytogenetic analysis, fluorescent in situ hybridization, restriction fragment
      length polymorphism, STR/VNTR analysis and real-time quantitative PCR, along with
      the various methods used to detect minimal residual disease (MRD) in different
      diseases such as chronic myeloid leukemia, acute myelomonocytic leukemia or acute
      lymphoblastic leukemia. The review mainly highlights the optimal methodological
      approach, which needs to be informative, sensitive and quantitatively accurate
      for MC detection. Future of post HSCT graft monitoring lies in the selection of
      the most accurate and sensitive technique to determine both MC and MRD. Such an
      approach would be helpful in not only determining relapse or rejection, but also
      in ascertaining various responses to different treatment modalities.

PMID- 15156164
TI  - Therapy-related myelodysplasia and leukemia occur infrequently following VP-16
      priming and autotransplantation without total body irradiation.
AB  - The use of VP-16 for stem cell mobilization has been cited as a significant risk
      factor for the development of therapy-related myelodysplasia/leukemia (tMDS/tAML)
      following autologous transplantation. The present study analyzed a large cohort
      of patients who underwent autotransplantation following stem cell mobilization
      with VP-16 and radiation-free preparation in order to determine the risk of
      tMDS/tAML. The estimated incidence of 9.9% at 7 years suggests that in the
      absence of TBI, VP-16 priming is not associated with an increased incidence of
      tMDS/tAML.

PMID- 15156166
TI  - Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell
      transplantation.
AB  - The majority of invasive aspergillosis (IA) in allogeneic stem cell
      transplantation (SCT) occurs during the post-engraftment period. We used Cox
      proportional hazards regression to evaluate post-engraftment IA risk in a cohort
      of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the
      effects of dose-intensity and duration of corticosteroids and other risk factors.
      Median duration of follow-up was 330 days. There were 19 cases of IA (overall
      8.8%) with 14 post-engraftment infections. In the final model, the risk of IA was
      greatest within 2 weeks of high-dose corticosteroids (HR 8.5, P=0.003), with risk
      extending to 4 weeks with doses of 0.25-1 mg/kg/day (HR 3.1, P=0.08). Ganciclovir
      was associated with greatest risk (HR 13.6). Grade 3 or 4 acute GVHD (HR 5.7) and
      secondary neutropenia (HR=1.3) were also additive risks. In the univariate
      analysis, corticosteroid doses of 0.25-1.0 mg/kg/day for any duration between 2
      and 10 weeks demonstrated prolonged risk for IA. Moderate doses of
      corticosteroids can confer an increased risk for IA for extended periods which is
      almost as marked as that conferred by higher doses. Knowledge of these risks may
      facilitate the development of targeted surveillance and prophylaxis strategies
      for prevention of IA.

PMID- 15156165
TI  - A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light
      chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study.
AB  - Stem cell transplantation was introduced as a new therapeutic modality for
      amyloidosis. The purpose of the current study was to determine the feasibility
      and toxicity of stem cell transplantation for amyloidosis in a cooperative group
      setting in which most participating institutions would have limited experience in
      managing the disorder. A total of 30 patients with biopsy-proven amyloidosis
      shown to be immunoglobulin light-chain type were enrolled on this trial. The
      protocol required mobilization of a minimum of 6 x 10(8) mononuclear cells/kg or
      5 x 10(6) CD34(+) cells/kg ideal body weight. These targets had to be achieved
      within seven collections. Patients with advanced hepatic, renal, or cardiac
      failure were excluded. End points included objective response rate and overall
      survival. The secondary end point of the protocol was nonhematologic toxicity.
      Accrual to the study was faster than expected. The overall response rate
      (hematologic and organ) was 64%, with three treatment-related deaths. Another
      patient died before day 30 of sudden cardiac death not treatment related. The
      median follow-up of surviving patients is 30.3 months. Median survival has not
      been reached. Stem cell transplantation for selected patients with amyloidosis is
      feasible in a cooperative group setting. A multicenter phase 3 trial of high-dose
      therapy is indicated.

PMID- 15156167
TI  - Development of BCR-ABL positive acute lymphoblastic leukemia in donor cells after
      allogeneic hematopoietic cell transplantation for Philadelphia-positive acute
      lymphoblastic leukemia.

PMID- 15156168
TI  - Unrelated cord blood transplant as salvage following non-engraftment of unrelated
      marrow transplant?

PMID- 15156169
TI  - Adoptive immunotherapy after bone marrow transplantation in a patient with
      relapsed acute myeloid leukaemia and severe psoriasis.

PMID- 15156173
TI  - Oncogenic potential of the RUNX gene family: 'overview'.
AB  - Runt-related (RUNX) gene family is composed of three members, RUNX1/AML1, RUNX2
      and RUNX3, and encodes the DNA-binding (alpha) subunits of the Runt domain
      transcription factor polyomavirus enhancer-binding protein 2 (PEBP2)/core-binding
      factor (CBF), which is a heterodimeric transcription factor. RUNX1 is most
      frequently involved in human acute leukemia. RUNX2 shows oncogenic potential in
      mouse experimental system. RUNX3 is a strong candidate as a gastric cancer tumor
      suppressor. The beta subunit gene of PEBP2/CBF is also frequently involved in
      chromosome rearrangements associated with human leukemia. In this Overview, I
      will summarize how this growing field has been formed and what are the
      challenging new frontiers for better understanding of the oncogenic potential of
      this gene family.

PMID- 15156174
TI  - Nomenclature for Runt-related (RUNX) proteins.

PMID- 15156175
TI  - Structure and regulated expression of mammalian RUNX genes.
AB  - The RUNX are key regulators of lineage-specific gene expression in major
      developmental pathways. The expression of RUNX genes is tightly regulated,
      leading to a highly specific spatio/temporal expression pattern and to distinct
      phenotypes of gene knockouts. This review highlights the extensive structural
      similarities between the three mammalian RUNX genes and delineates how regulation
      of their expression at the levels of transcription and translation are
      orchestrated into the unique RUNX expression pattern.

PMID- 15156176
TI  - Role of RUNX family members in transcriptional repression and gene silencing.
AB  - RUNX family members are DNA-binding transcription factors that regulate the
      expression of genes involved in cellular differentiation and cell cycle
      progression. The RUNX family includes three mammalian RUNX proteins (RUNX1, -2, 
      3) and two homologues in Drosophila. Experiments in Drosophila and mouse indicate
      that the RUNX proteins are required for gene silencing of engrailed and CD4,
      respectively. RUNX-mediated repression involves recruitment of corepressors such
      as mSin3A and Groucho as well as histone deacetylases. Furthermore, RUNX1 and
      RUNX3 associate with SUV39H1, a histone methyltransferase involved in gene
      silencing. RUNX1 is frequently targeted in human leukemia by chromosomal
      translocations that fuse the DNA-binding domain of RUNX1 to other transcription
      factors and corepressor molecules. The resulting leukemogenic fusion proteins are
      transcriptional repressors that form stable complexes with corepressors, histone
      deacetylases and histone methyltransferases. Thus, transcriptional repression and
      gene silencing through RUNX1 contribute to the mechanisms of leukemogenesis of
      the fusion proteins. Therapies directed at the associated cofactors may be
      beneficial for treatment of these leukemias.

PMID- 15156177
TI  - p300/CBP and cancer.
AB  - p300 and cyclic AMP response element-binding protein (CBP) are adenoviral E1A
      binding proteins involved in multiple cellular processes, and function as
      transcriptional co-factors and histone acetyltransferases. Germline mutation of
      CBP results in Rubinstein-Taybi syndrome, which is characterized by an increased
      predisposition to childhood malignancies. Furthermore, somatic mutations of p300
      and CBP occur in a number of malignancies. Chromosome translocations target CBP
      and, less commonly, p300 in acute myeloid leukemia and treatment-related
      hematological disorders. p300 mutations in solid tumors result in truncated p300
      protein products or amino-acid substitutions in critical protein domains, and
      these are often associated with inactivation of the second allele. A mouse model
      confirms that p300 and CBP function as suppressors of hematological tumor
      formation. The involvement of these proteins in critical tumorigenic pathways
      (including TGF-beta, p53 and Rb) provides a mechanistic route as to how their
      inactivation could result in cancer.

PMID- 15156178
TI  - Coordinate regulation of cell growth and differentiation by TGF-beta superfamily
      and Runx proteins.
AB  - Runx proteins regulate various biological processes, including growth and
      differentiation of hematopoietic cells, lymphocytes, osteoblasts, and gastric
      epithelial cells. Some of the biological activities of Runx proteins are
      reminiscent of those of transforming growth factor (TGF)-beta superfamily
      cytokines. Consistent with this notion, receptor-regulated Smads (R-Smads),
      signal mediators of the TGF-beta superfamily cytokines, and Runx proteins have
      been shown to physically interact with each other. R-Smads activated by TGF-beta
      and Runx proteins cooperatively induce synthesis of IgA in B lymphocytes, and
      those activated by bone morphogenetic proteins and Runx2 induce osteoblastic
      differentiation. Moreover, the R-Smad-Runx signaling pathways are regulated by an
      E3 ubiquitin ligase Smurf1, as well as a signal transducer of interferons, STAT1.
      Since Runxl and Runx3 are involved in the development of some cancers including
      acute leukemia and gastric cancer, it will be of interest to examine in detail
      whether TGF-beta-specific R-Smads and Runx proteins coordinately regulate growth
      and differentiation of hematopoietic cells and gastric epithelial cells.

PMID- 15156179
TI  - Core-binding factors in hematopoiesis and immune function.
AB  - Core binding factors are heterodimeric transcription factors containing a DNA
      binding Runx1, Runx2, or Runx3 subunit, along with a non DNA binding CBF beta
      subunit. All four subunits are required at one or more stages of hematopoiesis.
      This review describes the role of Runx1 and CBF beta in the initiation of
      hematopoiesis in the embryo, and in the emergence of hematopoietic stem cells. We
      also discuss the later stages of hematopoiesis for which members of the core
      binding factor family are required, as well as the recently described roles for
      these proteins in autoimmunity.

PMID- 15156180
TI  - Effects of the leukemia-associated AML1-ETO protein on hematopoietic stem and
      progenitor cells.
AB  - Insights into the pathogenesis of human leukemia have relied heavily on studies
      of the identified chromosomal translocations found in this group of malignant
      diseases. Acquired, balanced translocations in acute myelogenous leukemia (AML)
      generally involve transcriptional regulatory genes, whereas in the
      myeloproliferative disorders tyrosine kinases are frequently involved. These
      rearrangements alter the function of at least one and often both of the involved
      genes. In this review, we focus on the AML1-ETO (a.k.a. RUNX1-ETO) fusion
      protein, which is found in t(8;21)+ AML. Expression of AML1-ETO in human
      hematopoietic stem cells (HSCs) preferentially enhances their maintenance, as
      opposed to their differentiation. The direct effects of AML1-ETO on human and
      murine HSCs, and the potentially cooperating events that may contribute to its
      leukemogenic properties, are discussed.

PMID- 15156181
TI  - The 8;21 translocation in leukemogenesis.
AB  - A common chromosomal translocation in acute myeloid leukemia (AML) involves the
      AML1 (acute myeloid leukemia 1, also called RUNX1, core binding factor protein
      (CBF alpha), and PEBP2 alpha B) gene on chromosome 21 and the ETO (eight-twenty
      one, also called MTG8) gene on chromosome 8. This translocation generates an AML1
      ETO fusion protein. t(8;21) is associated with 12% of de novo AML cases and up to
      40% in the AML subtype M2 of the French-American-British classification.
      Furthermore, it is also reported in a small portion of M0, M1, and M4 AML
      samples. Despite numerous studies on the function of AML1-ETO, the precise
      mechanism by which the fusion protein is involved in leukemia development is
      still not fully understood. In this review, we will discuss structural aspects of
      the fusion protein and the accumulated knowledge from in vitro analyses on AML1
      ETO functions, and outline putative mechanisms of its leukemogenic potential.

PMID- 15156182
TI  - Molecular mechanisms of leukemogenesis by AML1/EVI-1.
AB  - The AML1/EVI-1 chimeric gene is generated by the t(3;21)(q26;q22) translocation
      and plays a pivotal role in progression of hematopoietic stem cell malignancies
      such as chronic myelocytic leukemia and myelodysplastic syndrome. In AML1/EVI-1,
      an N-terminal half of AML1 including a runt homology domain is fused to the
      entire zinc-finger EVI-1 protein. AML1 is essential for hematopoietic cell
      development in fetal liver and its lineage-specific differentiation in adult. In
      contrast, EVI-1 is barely expressed in normal hematopoietic cells, but it is
      overexpressed in chronic myelocytic leukemia in blastic crisis and
      myelodysplastic syndrome-derived leukemia. There are at least four mechanisms
      identified in AML1/EVI-1 fusion protein that possibly lead into malignant
      transformation of hematopoietic stem cells. Firstly, AML1/EVI-1 exerts dominant
      negative effects over AML1-induced transcriptional activation. Although target
      genes repressed by AML1/EVI-1 are still not known, binding competition to a
      specific DNA sequence and histone deacetylase recruitment through a co-repressor
      CtBP in EVI-1 part are conceivable underlying mechanisms for the dominant
      negative effects. Secondly, AML1/EVI-1 interferes with TGF beta signaling and
      antagonizes the growth-inhibitory effects of TGF beta. The first zinc-finger
      domain of EVI-1 associates with Smad3, a TGF beta signal transducer, and
      represses its transcriptional activity by recruiting histone deacetylase through
      CtBP that interacts with EVI-1. Thirdly, AML1/EVI-1 blocks JNK activity and
      prevents stress-induced apoptosis. AML1/EVI-1 associates with JNK through the
      first zinc-finger domain of EVI-1 and disturbs the association between JNK and
      its substrates. Lastly, AML1/EVI-1 enhances AP-1 activity by activating the c-Fos
      promoter depending on the second zinc-finger domain of EVI-1, and promotes cell
      proliferation. All these functions cooperatively contribute to the malignant
      transformation of the hematopoietic stem cells by AML1/EVI-1.

PMID- 15156183
TI  - ETO interacting proteins.
AB  - The 8;21 translocation produces a fusion between the ETO gene and that encoding
      the myeloid transcription factor AML1. The AML1-ETO fusion substitutes the
      majority of the ETO protein for the coregulator recruitment domains of AML1.
      Biochemical analyses of ETO have led to the identification of numerous
      interacting proteins including many corepressors. Importantly, the proteins
      interacting with ETO are different from those of wild-type AML1, suggesting that
      altered coregulator recruitment underlies the oncogenic properties of AML1-ETO.
      The list of corepressors capable of binding ETO includes histone deacetylases
      (HDACs) and components of distinct HDAC core complexes. These investigations have
      provided mechanistic insight into corepressor recruitment by ETO and clues to the
      leukemogenic activity of AML1-ETO.

PMID- 15156184
TI  - Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute
      lymphoblastic leukaemia.
AB  - Balanced chromosomal translocations are frequently associated with haematopoietic
      neoplasms and often involve genes that encode transcription factors, which play
      critical roles in normal haematopoiesis. Fusion oncoproteins that arise from
      chimeric genes generated by such translocations are usually stable and consistent
      molecular markers for a given disease subtype and contribute to the leukaemogenic
      processes. The t(12;21)(p13;q22) chromosomal translocation is the most frequent
      illegitimate gene recombination in paediatric cancer, occurring in approximately
      25% of common (c) B-cell precursor acute lymphoblastic leukaemia (cALL) cases.
      The rearrangement results in the in-frame fusion of the 5' region of the ETS
      related gene, TEL (ETV6), to almost the entire AML1 (RUNX1) locus and is
      associated with favourable prognosis following conventional therapeutic
      strategies. We discuss here the prenatal origins of the TEL/AML1 translocation as
      an initiating mutation, the role of TEL-AML1 in cellular transformation and the
      molecular mechanisms by which the chimeric protein imposes altered patterns of
      gene expression.

PMID- 15156185
TI  - Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia.
AB  - The RUNX1/AML1 gene is the most frequent target for chromosomal translocation in
      leukemia. In addition, recent studies have demonstrated point mutations in the
      RUNX1 gene as another mode of genetic alteration in development of leukemia.
      Monoallelic germline mutations in RUNX1 result in familial platelet disorder
      predisposed to acute myelogenous leukemia (FPD/AML). Sporadic point mutations are
      frequently found in three leukemia entities: AML M0 subtype, MDS-AML, and
      secondary (therapy-related) MDS/AML. Therapy-related leukemias resulting from
      anticancer treatments are not uncommon, and the incidence of RUNX1 point
      mutations appears comparable to the incidence of the t(8;21) AML M2 subtype and
      the inv(16) AML M4Eo subtype. Half of the point mutations in M0 cases are
      biallelic, although the frequency varies with ethnicity. Most of the RUNX1
      mutations are clustered in the Runt domain and result in defective DNA binding
      but active beta-subunit binding, which is consistent with three-dimensional
      structural findings and may explain the dominant inhibitory effects. Unlike the
      classical tumor suppressor genes requiring biallelic inactivation,
      haploinsufficient RUNX1 is apparently leukemogenic. However, RUNX1 abnormalities
      per se are insufficient to cause full-blown leukemia. Intensive investigation of
      cooperating genetic alterations should elucidate leukemic mechanisms.

PMID- 15156186
TI  - Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11.
AB  - Inv(16)(p13q22) is associated with acute myeloid leukemia subtype M4Eo that is
      characterized by the presence of myelomonocytic blasts and atypical eosinophils.
      This chromosomal rearrangement results in the fusion of CBFB and MYH11 genes. CBF
      beta normally interacts with RUNX1 to form a transcriptionally active nuclear
      complex. The MYH11 gene encodes the smooth muscle myosin heavy chain. The CBF
      beta-SMMHC fusion protein is capable of binding to RUNX1 and form dimers and
      multimers through its myosin tail. Previous results from transgenic mouse models
      show that Cbfb-MYH11 is able to inhibit dominantly Runx1 function in
      hematopoiesis, and is a key player in the pathogenesis of leukemia. In recent
      years, molecular and cellular biological studies have led to the proposal of
      several models to explain the function of CBF beta-SMMHC. In this review, we will
      first focus our attention on the molecular mechanisms proposed in the recent
      publications. We will next examine recent gene expression profiling studies on
      inv(16) leukemia cells. Finally, we will describe a recent study from one of our
      labs on the identification of cooperating genes for leukemogenesis with CBFB
      MYH11.

PMID- 15156187
TI  - The Runx genes: lineage-specific oncogenes and tumor suppressors.
AB  - The Runx genes present a challenge to the simple binary classification of cancer
      genes as oncogenes or tumor suppressors. There is evidence that loss of function
      of two of the three mammalian Runx genes promotes cancer, but in a highly lineage
      restricted manner. In human leukemias, the RUNX1 gene is involved in various
      chromosomal translocation events that create oncogenic fusion proteins, at least
      some of which appear to function as dominant-negative inhibitors of the normal
      gene product. Paradoxically, evidence is mounting that structurally intact Runx
      genes are also oncogenic when overexpressed. All the three murine genes act as
      targets for transcriptional activation by retroviral insertional mutagenesis, and
      the oncogenic potential of Runx2 has been confirmed in transgenic mice. Moreover,
      the RUNX1 gene is often amplified or overexpressed in cases of acute leukemia.
      The state of progress in elucidating the oncogenic roles of the Runx genes is the
      subject of this review, and we draw together recent observations in a tentative
      model for the effects of Runx deregulation on hematopoietic cell differentiation.
      We suggest that lineage-specific factors determine the sensitivity to the
      oncogenic effects of loss or overexpression of Runx factors.

PMID- 15156189
TI  - Growth regulation of gastric epithelial cells by Runx3.
AB  - RUNX3: is expressed by gastric epithelial cells throughout development. Mice
      whose Runx3 gene has been knocked out died soon after birth. In the knockout
      mouse, gastric epithelia exhibited hyperplasia and epithelial apoptosis was
      suppressed. Analysis using a primary culture system for the epithelial cells
      suggested that this is caused by the reduced sensitivity of Runx3-/- gastric
      epithelial cells to the growth-inhibiting and apoptosis-inducing activities of
      TGF-beta. In human and mouse gastric cancer cell lines, RUNX3/Runx3 was silenced
      due to hypermethylation of CpG islands in the promoter region. Exogenous
      expression of RUNX3 in the cells that do not express the endogenous gene caused
      an inhibition of growth both in vivo and in vitro. These observations indicate
      that Runx3 is a major growth regulator of gastric epithelial cells, and that it
      is deeply involved in gastric tumorigenesis in both humans and mice.

PMID- 15156188
TI  - Runx2 control of organization, assembly and activity of the regulatory machinery
      for skeletal gene expression.
AB  - We present an overview of Runx involvement in regulatory mechanisms that are
      requisite for fidelity of bone cell growth and differentiation, as well as for
      skeletal homeostasis and the structural and functional integrity of skeletal
      tissue. Runx-mediated control is addressed from the perspective of support for
      biological parameters of skeletal gene expression. We review recent findings that
      are consistent with an active role for Runx proteins as scaffolds for
      integration, organization and combinatorial assembly of nucleic acids and
      regulatory factors within the three-dimensional context of nuclear architecture.

PMID- 15156190
TI  - Tumor suppressor activity of RUNX3.
AB  - Recent analyses have revealed that RUNX family members play important roles in
      both normal developmental processes and carcinogenesis. Of the three known RUNX
      family members, RUNX3 has been shown to be involved in neurogenesis of the dorsal
      root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium.
      Deletion of the Runx3 locus in mice resulted in hyperplasia of the gastric
      epithelium due to the stimulation of proliferation and suppression of apoptosis
      that was accompanied by a reduced sensitivity to TGF-beta1. In primary human
      gastric cancer specimens, RUNX3 is frequently inactivated by allele loss or gene
      silencing due to promoter hypermethylation. The tumorigenicity of human gastric
      cancer cell lines in nude mice decreased as the level of RUNX3 expression
      increased, which indicates that RUNX3 is a bona fide tumor suppressor of gastric
      cancers.

PMID- 15156191
TI  - Epigenetic gene silencing by Runx proteins.
AB  - Runx family proteins have the potential for either activating or suppressing gene
      expression in a context-dependent manner. There are several mechanisms by which
      transcriptional repression can occur. A wide range of locus inactivation, that is
      often called gene silencing, is thought to be achieved by chromatin
      modifications. Recently, Runx family proteins were found to have an essential
      role in either temporal transcriptional repression or irreversible epigenetic
      silencing at the CD4 locus through binding to a CD4 silencer at different stages
      of development. These findings link Runx function to epigenetic gene regulation,
      and shed new light on the mechanisms by which Runx represses target gene
      expression.

PMID- 15156192
TI  - Homologs of RUNX and CBF beta/PEBP2 beta in C. elegans.
AB  - RUNX proteins are evolutionarily well-conserved transcription factors that are
      involved in essential aspects of the development of metazoan animals ranging from
      nematodes to humans. Genetic or epigenetic defects in any one of the three RUNX
      proteins in humans cause severe diseases. Although much is known about the
      functions and signaling pathways of the RUNX proteins through the use of
      mammalian systems, there are still gaps in our knowledge with regard to the
      functions of the RUNX proteins in normal development and disease states.
      Recently, the nematode Caenorhabditis elegans was revealed to bear one RUNX
      homolog (RNT-1) and one homolog of the RUNX protein partner CBF beta/PEBP2 beta
      (BRO-1). The expression patterns and biological functions of RNT-1 and the manner
      in which it is regulated are all comparable to what has been observed for the
      mammalian RUNX proteins. Thus, the nematode system is a promising model system
      for elucidating the functions and regulation of Runt proteins. In addition, it
      has recently emerged that the RNT-1 protein is involved in a transforming growth
      factor beta signaling pathway. The bro-1 gene encoding the CBF beta homolog is
      exclusively expressed in the hypodermis, not in the intestine, which indicates
      that additional tissue-specific cofactors in the intestine might exist. The
      possible autoregulation of RNT-1 expression by RNT-1/BRO-1 in the hypodermal
      cells is also discussed.

PMID- 15156193
TI  - Androgen receptor level controlled by a suppressor complex lost in an androgen
      independent prostate cancer cell line.
AB  - Androgen receptor (AR) overexpression is one of the characteristics of prostate
      cancer (PC) that progresses to hormone independence. An androgen-independent (AI)
      derivative, with much higher AR-mRNA and protein levels than the parental LNCaP
      cell line, whose proliferation was androgen dependent (AD), was used to explore
      the mechanism of AR overexpression. We found that a suppressor element (ARS),
      previously identified in mouse AR and located in the 5'-untranslated region of
      human AR gene, malfunctions in AI cells. Transfection of constructs that included
      ARS element into AD cells reduced the transactivating activities of both AR
      promoter and a heterologous SV40 promoter. The deletion of ARS resulted in an
      eightfold increase in AR-promoter activity in AD cells, but had no effect in AI
      cells. Moreover, the nuclear extracts of AD cells contained proteins that
      produced a specific, ARS-binding complex, while this complex appeared to have
      been lost from AI cells. Most importantly, treatment of AI cells with a
      demethylating agent or histone deacetylase inhibitors restored the lost ARS
      binding complex. The restoration of the complex coincided with a reduced
      expression of AR-mRNA and protein and a reduced rate of AR-gene transcription,
      determined by nuclear run-on experiment. Thus, epigenetic transcriptional
      silencing of the suppressor protein(s) may be responsible for AR overexpression
      in AI cells, and its reversal in hormone-independent PC may normalize AR levels
      and restore their hormone dependence.

PMID- 15156194
TI  - Utilization of the CBP but not the p300 co-activator by human T-lymphotropic
      virus type-2 Tax for p53 inhibition.
AB  - We previously reported, both in transfected cells and in human T-cell leukemia
      virus type-2 subtype B infected cells, that the viral transactivator Tax-2B
      protein could inhibit p53 functions. We have now investigated the mechanism
      through which Tax-2B represses p53 using GFPTax-2B fusion proteins. We present
      evidence that Tax-2B inhibition of p53 function is not linked to CREB/ATF
      activation, but is uniquely correlated with the interaction of CREB binding
      protein (CBP), but not p300, with the C-terminus of Tax-2B. Wild type, but not a
      Tax-2B-M47 mutant, inhibits p53 function in adherent cells. We demonstrate that
      both Tax-2B and Tax-2B-M47 can bind p300, while Tax-2B-M47 is impaired for CBP
      binding. Importantly, transfection of increasing amounts of CBP but not p300 or
      p300/CBP-associated factor (P/CAF) could rescue p53 transcriptional activity in
      the presence of Tax-2B in nonlymphocytic cells. In lymphoid cells, Tax-2B
      mediated inhibition of p53 is correlated with the NF-kappaB pathway activation
      and could be prevented by the overexpression of an IkappaBalpha mutant. Given the
      similarities between the functional domains of CBP and p300, these results are
      intriguing and suggest that Tax-2B must bind the CR2 domain of CBP, but not that
      of p300 in order to repress p53.

PMID- 15156195
TI  - Depletion of physiological levels of the human TID1 protein renders cancer cell
      lines resistant to apoptosis mediated by multiple exogenous stimuli.
AB  - The human homologue of the Drosophila tumor suppressor lethal (2) tumorous
      imaginal discs (l(2)tid) gene, hTID1, encodes two proteins derived from alternate
      mRNA splicing. The splice variants TidL and TidS were previously reported from
      protein overexpression and dominant-negative mutant protein studies to exhibit
      opposing biological activities in response to exogenous cytotoxic stimuli. TidL
      was found to promote apoptosis while TidS suppressed it. To elucidate the
      physiological function of hTID1, we depleted hTID1 proteins using the technique
      of RNA interference (RNAi). Here, we show that cells essentially lacking
      expression of hTID1 proteins are protected from cell death in response to
      multiple stimuli, including cisplatin, tumor necrosis factor alpha/cycloheximide
      and mitomycin C. We also generated stable cell populations depleted of hTID1
      proteins by RNAi using DNA vectors. In addition to apoptosis resistance, stable
      hTID1 knockdown cells exhibited an enhanced ability for anchorage-independent
      growth, as measured by an increase in soft-agar colony formation. These results
      suggest that hTID1 functions as an important cell death regulator and raise the
      interesting possibility that hTID1 could exert tumor suppressor activity.

PMID- 15156196
TI  - Nucleic acid 3'-end recognition by the Argonaute2 PAZ domain.
AB  - We describe the solution structures of the Argonaute2 PAZ domain bound to RNA and
      DNA oligonucleotides. The structures reveal a unique mode of single-stranded
      nucleic acid binding in which the two 3'-terminal nucleotides are buried in a
      hydrophobic cleft. We propose that the PAZ domain contributes to the specific
      recognition of siRNAs by providing a binding pocket for their characteristic two
      nucleotide 3' overhangs.

PMID- 15156197
TI  - Structural visualization of polarization fatigue in epitaxial ferroelectric oxide
      devices.
AB  - Ferroelectric oxides, such as Pb(Zr,Ti)O(3), are useful for electronic and
      photonic devices because of their ability to retain two stable polarization
      states, which can form the basis for memory and logic circuitry. Requirements for
      long-term operation of practical devices such as non-volatile RAM (random access
      memory) include consistent polarization switching over many (more than 10(12))
      cycles of the applied electric field, which represents a major challenge. As
      switching is largely controlled by the motion and pinning of domain walls, it is
      necessary to develop suitable tools that can directly probe the ferroelectric
      domain structures in operating devices-thin-film structures with electrical
      contacts. A recently developed synchrotron X-ray microdiffraction technique
      complements existing microscopic probes, and allows us to visualize directly the
      evolution of polarization domains in ferroelectric devices, through metal or
      oxide electrodes, and with submicrometre spatial resolution. The images reveal
      two regimes of fatigue, depending on the magnitude of the electric field pulses
      driving the device: a low-field regime in which fatigue can be reversed with
      higher electric field pulses, and a regime at very high electric fields in which
      there is a non-reversible crystallographic relaxation of the epitaxial
      ferroelectric film.

PMID- 15156198
TI  - Direct-bandgap properties and evidence for ultraviolet lasing of hexagonal boron
      nitride single crystal.
AB  - The demand for compact ultraviolet laser devices is increasing, as they are
      essential in applications such as optical storage, photocatalysis, sterilization,
      ophthalmic surgery and nanosurgery. Many researchers are devoting considerable
      effort to finding materials with larger bandgaps than that of GaN. Here we show
      that hexagonal boron nitride (hBN) is a promising material for such laser devices
      because it has a direct bandgap in the ultraviolet region. We obtained a pure hBN
      single crystal under high-pressure and high-temperature conditions, which shows a
      dominant luminescence peak and a series of s-like exciton absorption bands around
      215 nm, proving it to be a direct-bandgap material. Evidence for room-temperature
      ultraviolet lasing at 215 nm by accelerated electron excitation is provided by
      the enhancement and narrowing of the longitudinal mode, threshold behaviour of
      the excitation current dependence of the emission intensity, and a far-field
      pattern of the transverse mode.

PMID- 15156199
TI  - Stacking fault energies and slip in nanocrystalline metals.
AB  - The search for deformation mechanisms in nanocrystalline metals has profited from
      the use of molecular dynamics calculations. These simulations have revealed two
      possible mechanisms; grain boundary accommodation, and intragranular slip
      involving dislocation emission and absorption at grain boundaries. But the
      precise nature of the slip mechanism is the subject of considerable debate, and
      the limitations of the simulation technique need to be taken into consideration.
      Here we show, using molecular dynamics simulations, that the nature of slip in
      nanocrystalline metals cannot be described in terms of the absolute value of the
      stacking fault energy-a correct interpretation requires the generalized stacking
      fault energy curve, involving both stable and unstable stacking fault energies.
      The molecular dynamics technique does not at present allow for the determination
      of rate-limiting processes, so the use of our calculations in the interpretation
      of experiments has to be undertaken with care.

PMID- 15156200
TI  - Topological complexity and the dynamics of coarsening.
AB  - Coarsening or Ostwald ripening occurs in a vast array of two-phase systems.
      Coarsening results in a decrease in the interfacial area per unit volume and a
      concomitant increase in the size scale of the interfacial morphology. Much is
      known about the coarsening process in two-phase mixtures consisting of a
      polydisperse array of spherical particles. In contrast, in many two-phase
      mixtures, such as those found in two-phase polymers, ceramics, dendritic solid
      liquid mixtures and order-disorder transformations, the interfaces are both
      interconnected and have a spatially varying mean curvature. Here we show that the
      morphological evolution of these topologically complex systems during coarsening
      can be quantified by measuring the probability of finding a patch of interface
      with a given curvature tensor. We find that the morphological evolution is
      described by the flow of probability density in this curvature space that is
      induced by the coarsening process. The hallmark of our approach is a close
      coupling between experiment and theory; we use the experimentally measured three
      dimensional microstructure as an input to a phase-field calculation that then
      determines the flow in curvature space. The methodology is general, and
      applicable to many systems undergoing coarsening, regardless of their topology.

PMID- 15156201
TI  - mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through
      regulation of apoptotic and HIF-1-dependent pathways.
AB  - Loss of PTEN function leads to activation of phosphoinositide 3-kinase (PI3K)
      signaling and Akt. Clinical trials are now testing whether mammalian target of
      rapamycin (mTOR) inhibition is useful in treating PTEN-null cancers. Here, we
      report that mTOR inhibition induced apoptosis of epithelial cells and the
      complete reversal of a neoplastic phenotype in the prostate of mice expressing
      human AKT1 in the ventral prostate. Induction of cell death required the
      mitochondrial pathway, as prostate-specific coexpression of BCL2 blocked
      apoptosis. Thus, there is an mTOR-dependent survival signal required downstream
      of Akt. Bcl2 expression, however, only partially restored intraluminal cell
      growth in the setting of mTOR inhibition. Expression profiling showed that Hif-1
      alpha targets, including genes encoding most glycolytic enzymes, constituted the
      dominant transcriptional response to AKT activation and mTOR inhibition. These
      data suggest that the expansion of AKT-driven prostate epithelial cells requires
      mTOR-dependent survival signaling and activation of HIF-1 alpha, and that
      clinical resistance to mTOR inhibitors may emerge through BCL2 expression and/or
      upregulation of HIF-1 alpha activity.

PMID- 15156202
TI  - Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents
      inflammatory bone destruction in vivo.
AB  - Bone destruction is a pathological hallmark of several chronic inflammatory
      diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced
      bone loss of this sort results from elevated numbers of bone-resorbing
      osteoclasts. Gene targeting studies have shown that the transcription factor
      nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast
      differentiation, and blocking NF-kappa B is a potential strategy for preventing
      inflammatory bone resorption. We tested this approach using a cell-permeable
      peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal
      transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF
      kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition,
      this peptide significantly reduced the severity of collagen-induced arthritis in
      mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta,
      abrogating joint swelling and reducing destruction of bone and cartilage.
      Therefore, selective inhibition of NF-kappa B activation offers an effective
      therapeutic approach for inhibiting chronic inflammatory diseases involving bone
      resorption.

PMID- 15156203
TI  - PrPSc accumulation in myocytes from sheep incubating natural scrapie.
AB  - Because variant Creutzfeldt-Jakob disease (vCJD) in humans probably results from
      consumption of products contaminated with tissue from animals with bovine
      spongiform encephalopathy, whether infectious prion protein is present in
      ruminant muscles is a crucial question. Here we show that experimentally and
      naturally scrapie-affected sheep accumulate the prion protein PrP(Sc) in a
      myocyte subset. In naturally infected sheep, PrP(Sc) is detectable in muscle
      several months before clinical disease onset. The relative amounts of PrP(Sc)
      suggest a 5,000-fold lower infectivity for muscle as compared to brain.

PMID- 15156204
TI  - cAMP and Schwann cells promote axonal growth and functional recovery after spinal
      cord injury.
AB  - Central neurons regenerate axons if a permissive environment is provided; after
      spinal cord injury, however, inhibitory molecules are present that make the local
      environment nonpermissive. A promising new strategy for inducing neurons to
      overcome inhibitory signals is to activate cAMP signaling. Here we show that cAMP
      levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after
      spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV
      inhibitor rolipram prevents this decrease and when combined with Schwann cell
      grafts promotes significant supraspinal and proprioceptive axon sparing and
      myelination. Furthermore, combining rolipram with an injection of db-cAMP near
      the graft not only prevents the drop in cAMP levels but increases them above
      those in uninjured controls. This further enhances axonal sparing and
      myelination, promotes growth of serotonergic fibers into and beyond grafts, and
      significantly improves locomotion. These findings show that cAMP levels are key
      for protection, growth and myelination of injured CNS axons in vivo and recovery
      of function.

PMID- 15156205
TI  - The chlamydia problem in New Zealand.

PMID- 15156206
TI  - The challenge of improving cardiac care in secondary centres.

PMID- 15156207
TI  - Rates of Chlamydia trachomatis testing and chlamydial infection in pregnant
      women.
AB  - AIMS: To determine the rate of Chlamydia trachomatis testing and chlamydial
      infection in pregnancy (by auditing a community medical laboratory database).
      METHODS: Data for women registered with a maternity care provider between 1999
      and 2002 were matched with a community medical laboratory database for patients
      who met one of three criteria: tested for C. trachomatis, or had a first or
      second antenatal blood screen at that laboratory. The rate of C. trachomatis
      testing and of chlamydial infection was then calculated in this sample. RESULTS:
      The overall rate of C. trachomatis testing for 6614 matched deliveries was 37.5%,
      with 4.8% of those tests positive for chlamydial infection. The rate of testing
      differed significantly between age-bands (p<0.0001), and by ethnicity (p<0.0001).
      The rate of infection showed a significant effect of age (p<0.0001) and ethnicity
      (p<0.0001). Maori and Pacific women, and those under the age of 25 years, had the
      highest rates--both of testing and of C. trachomatis infection. CONCLUSIONS:
      There is a high rate of maternal C. trachomatis in under 25-year-olds, and in
      Maori and Pacific women, together with incomplete testing for the infection in
      pregnancy. This highlights the need to instigate routine testing for C.
      trachomatis in pregnancy--to reduce the significant, yet preventable, morbidity
      associated with chlamydia in both the mother and the neonate.

PMID- 15156208
TI  - Management of unstable angina and non-ST-elevation myocardial infarction: do
      cardiologists do it better? A comparison of secondary and tertiary centre
      management in New Zealand.
AB  - BACKGROUND: Internationally, differences have been noted in how specialist
      cardiologists and general physicians manage acute coronary syndromes (ACS).
      Whether a similar practice difference exists in New Zealand is unclear. AIM: To
      test the hypothesis that management differences exist between cardiologists and
      general physicians in patients presenting with a non-ST-segment elevation acute
      coronary syndrome in a New Zealand setting-and whether these differences (if
      present) impact on patient outcome. METHODS: A retrospective chart review of 324
      consecutive patients presenting with a non-ST-segment elevation acute coronary
      syndrome to Taranaki Base and Waikato Hospitals from 1 January 1999 was
      undertaken. Patients in Taranaki were managed by general physicians and in
      Waikato they were managed by cardiologists. RESULTS: Patients presenting to
      Taranaki Base Hospital were more likely to have high-risk ECG changes with ST
      segment depression noted in 34.4% of patients there compared to 16.8% of patients
      in Waikato (p<0.001). Medical management during patient stabilisation was similar
      in Taranaki and Waikato with high use of anti-thrombotic (89%) and anti-platelet
      therapy (94%), respectively. However angiography (5.1% versus 23.4%; p=0.0045)
      and revascularisation procedures (4% versus 16.7%; p=0.0002) were performed less
      frequently in Taranaki. No significant difference was noted in mortality at 6
      months (9.6% in Waikato versus 13.4% in Taranaki; p=0.4) Readmission rates were
      also similar; occurring overall in approximately one-quarter of the study
      population. CONCLUSION: In New Zealand, differences exist in how cardiologists
      and general physicians manage non-ST-elevation acute coronary syndrome. In
      particular, the low referral rates for angiography by general physicians is of
      concern and requires correction as current best-practice guidelines suggest high
      risk patients are disadvantaged by a conservative approach to management.

PMID- 15156209
TI  - The New Zealand child work-related fatal injury study: 1985-1998.
AB  - AIMS: To estimate the numbers and rates of work-related fatal injury for children
      under the age of 15 years. METHODS: Potential cases of work-related injury deaths
      of persons aged <15 years of age were identified from the national electronic
      mortality data-files for the period 1985-1998 inclusive. The circumstances of the
      death in each fatality incident were reviewed directly from coronial files to
      determine work-relatedness. RESULTS: A total of 87 workplace work-related
      fatalities were identified. The vast majority of children identified were fatally
      injured while a bystander to another person's work. Workplace bystander
      involvement was found to vary by age, with the majority of workers identified
      aged 10-14 years old. With a third of all fatalities, the agricultural industry
      was the most common industry for workplace work-related fatalities in children.
      In the period 1985-94, children <15 years of age were found to account for 46% of
      New Zealand's total workplace bystander deaths. CONCLUSIONS: Children contribute
      significantly to the overall burden of work-related fatal injury in New Zealand,
      especially as bystanders to other people's work. The high contribution to
      bystander deaths by children aged <15 years suggests that hazard control in
      certain work settings is lacking.

PMID- 15156210
TI  - Oral health status and oral treatment needs of dependent elderly people in
      Christchurch.
AB  - AIM: To describe the general health, oral health status, and treatment needs of
      dependent older people living in Christchurch rest homes. METHODS: 210 Grade 3
      residents from seven randomly selected care facilities were examined for:
      dental/denture status, caries, periodontal disease, and oral cleanliness.
      RESULTS: Age ranged from 65 to 103 with an average age of 84.6 years. The female
      to-male ratio was 3:1. Thirty-two percent of residents were dentate (average 14
      teeth). This figure was up from 16-19% one decade ago (p<0.01; chi-squared test).
      Sixty-five percent of dentate residents had caries. Each dentate person had an
      average of 2.38 teeth with carious lesions in the root or crown. 51.5% of
      residents required restorative treatment and 38.2% required an extraction. Twenty
      residents had at least one 'carious stump'. Eighty-two percent of residents
      required scaling of the teeth. Two thirds had no natural teeth, and one third of
      those with dentures required treatment. Eighty-nine residents (42%) were unable
      to communicate about past dental behaviours. CONCLUSIONS: These data indicate
      that (compared to one decade ago) more dependent elderly people are retaining
      their natural teeth--but they are keeping no more teeth, and the health of the
      teeth has not improved. Most elderly people do not regularly receive dental
      assessments or care.

PMID- 15156211
TI  - Lack of association between long-term illness and infectious intestinal disease
      in New Zealand.
AB  - AIMS: To investigate whether the increase in notified cases of infectious
      intestinal disease in New Zealand from 1988 to 2001 has resulted in a concurrent
      increase in associated secondary illness cases. METHODS: National surveillance
      system data were compared to hospital discharge data. RESULTS: No statistically
      significant correlation between the number of cases of campylobacteriosis and
      Guillain-Barre syndrome (GBS) was found. There was no statistically significant
      correlation between the number of cases of campylobacteriosis, salmonellosis,
      shigellosis, and any of the categories of reactive arthritis; apart from two
      correlations with campylobacteriosis: with arthropathy associated with Reiter's
      disease and nonspecific urethritis (Pearson correlation R2=0.69; p<0.02) and
      unspecified infective arthritis (Pearson correlation R2=0.75; p<0.008). The later
      category is likely to include cases of both infective and non-infective
      aetiology. CONCLUSION: In New Zealand, infectious intestinal diseases are not
      making a significant contribution to the burden of hospitalisation for reactive
      arthritis or GBS.

PMID- 15156212
TI  - Familial Mediterranean fever: 36 years to diagnosis.

PMID- 15156213
TI  - Complete atrioventricular block in Becker muscular dystrophy.

PMID- 15156214
TI  - Helicobacter pylori: a historical perspective 1983-2003.

PMID- 15156215
TI  - Homocysteine and progression of coronary artery disease.
AB  - BACKGROUND: Hyperhomocysteinemia is one of the newly recognised risk factors of
      coronary artery disease (CAD). The role of hyperhomocysteinemia in the
      development of atherosclerosis has been controversial. AIM: To assess
      homocysteine (Hcy) plasma concentration in patients with CAD and to correlate Hcy
      level with some cardiovascular risk factors. METHODS: The study group consisted
      of 150 males aged <55 years (mean age 49.5+/-5.7 years) with stable CAD. Lipid
      and carbohydrate profiles as well as Hcy, folic acid and vitamin B(12) serum
      concentration were assessed, and correlated with such cardiovascular risk factors
      as cigarette smoking, hypertension, obesity and a history of myocardial
      infarction. RESULTS: Mean Hcy plasma concentration was 11.81+/-3.75 micro mol/L.
      In patients with Hcy >11.21 micro mol/L (median value) a lower level of folic
      acid and vitamin B12 as well as reduced ejection fraction and glomerular
      filtration rate were found when compared to patients with Hcy level <11.21 micro
      mol/L. In addition, creatinine concentration, mean patient's age, proportion of
      patients who smoked cigarettes and the number of affected coronary arteries were
      significantly higher in patients with an increased level of Hcy. The Hcy plasma
      concentration positively correlated with the progression of hypertension,
      creatinine level and the number of coronary vessels with stenosis. A significant
      negative correlation between Hcy and folic acid as well as vitamin B12
      concentrations was documented. In patients with a three-vessel CAD, Hcy
      concentration was 12.46+/-3.85 micro mol/L and was significantly higher (p<0.03)
      compared with patients with a less advanced CAD. In the group of patients with
      diabetes the mean Hcy concentration increased with the number of affected
      coronary vessels (p<0.02) and reached the highest values in patients with a three
      vessel CAD (15.38+/-7.28 micro mol/L). CONCLUSIONS: There is a significant
      relationship between homocysteine plasma concentration and the incidence as well
      as progression of CAD. This association is particularly evident in patients with
      diabetes.

PMID- 15156216
TI  - Risk factors of atrial fibrillation in patients with Wolff-Parkinson-White
      syndrome.
AB  - BACKGROUND: Atrial fibrillation (AF) in patients with WPW syndrome may be a life
      threatening arrhythmia. AIM: To identify risk factors of AF and their prognostic
      significance in patients with WPW syndrome. METHODS: Clinical and
      electrophysiological parameters of 239 patients with WPW syndrome, who underwent
      successful RF ablation, were analysed using logistic regression and multivariate
      analysis. One hundred eight patients had no history of AF whereas the remaining
      81 patients had previous spontaneous AF episodes. Long-term follow-up data (mean
      29+/-23 months, range 1-99 months) were available in 136 patients (87 without AF
      and 49 with AF). RESULTS: Patients with AF were significantly older, more
      frequently of male gender and had more often a history of syncope than patients
      without AF. There were two peaks of AF occurrence - in the third and in the fifth
      decade of life. Fourteen patients had a history of ventricular fibrillation - 11
      patients with AF vs 3 patients without AF (p=0.0016). Patients with a history of
      AF were more prone to AF induced during electrophysiological study and had less
      frequently concealed accessory pathways. CONCLUSIONS: Age, gender and a history
      of syncope are the independent risk factors of AF in patients with WPW syndrome.
      Anterograde conduction via accessory pathway is of major importance in the
      development of AF. RF ablation of an accessory pathway should be performed early
      because the risk of the procedure is small and there is an increasing risk of AF
      with ageing.

PMID- 15156217
TI  - Changes in the cardiovascular system during pregnancy in women with secondary
      atrial septal defect.
AB  - BACKGROUND: The secundum atrial septal defect (ASD II) is, after bicuspid aortic
      valve, the second most frequent congenital heart disease. In the majority of
      females with ASD II the course of pregnancy is uncomplicated, however, pregnancy
      related cardiovascular changes may affect hemodynamic parameters of the defect.
      AIM: To assess cardiovascular changes in pregnant females with ASD II. METHODS:
      The study group consisted of 54 pregnant females with ASD II and 30 control
      healthy pregnant women. NYHA class, standard ECG, 24-hour ambulatory ECG
      monitoring and echocardiography were analysed in the second and third trimester
      of pregnancy as well as during puerperium. RESULTS AND CONCLUSIONS: (1) Due to
      the relatively small sample of population studied and limitations of the usage of
      NYHA classification in pregnant women, the relationship between ASD II and the
      development of heart failure during pregnancy could not be definitely proved. (2)
      An increase in the right ventricular and right atrial enlargement was
      significantly greater in pregnant women with ASD II compared with healthy
      pregnant females. Also indirect parameters of the right ventricular strain
      (paradoxical systolic movement of the interventricular septum or tricuspid
      regurgitation) were more frequent in patients with ASD II rather than in
      controls. These alterations were accompanied by a significant decrease in the
      mean value of the Qp/Qs index which may suggest pregnancy-related favourable
      changes in the hemodynamic consequences of the defect - a decrease in the left-to
      right shunt. (3) Paroxysmal supraventricular tachycardia was the most frequent
      cardiac arrhythmia in pregnant women with ASD II.

PMID- 15156218
TI  - Lipid profile during the first 24 hours after myocardial infarction has
      significant prognostic value.
AB  - AIMS: A high level of total cholesterol and LDL-cholesterol disturbs the
      endothelial function. Thus it can be expected, that hypercholesterolaemia may
      unfavourably influence the course of the acute myocardial infarction. The aim of
      the study was to check whether patients with lipid levels above normal during the
      first hours of myocardial infarction have an unfavourable clinical outcome.
      METHODS AND RESULTS: The study group consisted of 348 patients (216 males, aged
      65.7+/-12 years) with acute myocardial infarction hospitalized up to 24 hours
      after the onset of symptoms. Blood samples for lipid profile were taken on the
      first day of hospitalization, in the morning, while fasting. 109 (31%) patients
      had a complicated in-hospital course of infarction (i.e. death, recurrent
      ischaemia, serious arrhythmias and/or conduction disturbances, heart failure).
      The total cholesterol and LDL-cholesterol levels were higher in the patients with
      complicated than in the patients with uncomplicated clinical course of
      infarction: 243+/-40.7 vs 211.2+/-40.6 mg/dl, p<0.001 and 156+/-35.0 vs 132.6+/
      35.2 mg/dl p<0.001, respectively. CONCLUSIONS: Higher levels of total cholesterol
      and LDL cholesterol during the first 24 hours of acute myocardial infarction have
      a strong negative prognostic value, what suggests the use of statins as early as
      possible in acute myocardial infarction.

PMID- 15156219
TI  - Implantable cardioverter-defibrillators in children.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICD) have been increasingly
      used in adult patients for the prevention of sudden cardiac death (SCD). The
      usefulness and feasibility of ICD implantation in children have been less well
      established. AIM: To analyse indications, results and safety of ICD therapy in
      children. METHODS: ICDs were implanted in seven children, aged from 6 to 17
      years. All patients underwent cardiological evaluation which included analysis of
      medical history, physical examination, chest X-ray, standard ECG, 24-hour Holter
      ECG monitoring and echocardiography. RESULTS: In five children devices were
      implanted due to aborted sudden death (ventricular fibrillation) whereas in the
      remaining two - as a primary prevention of SCD. Three children had hypertrophic
      cardiomyopathy, one - dilated cardiomyopathy, one - mitral valve prolapse and QT
      prolongation, one - congenital long QT syndrome and the remaining patient -
      idiopathic ventricular tachycardia. Single-chamber devices were implanted in six
      children, and dual-chamber system - in one patient. In all patients endocardial
      leads were implanted and ICD pocket was formed under the greater pectoral muscle.
      During follow-up ranging between four months to 5.4 years, four children
      developed ventricular fibrillation or ventricular tachycardia which were
      terminated by appropriate ICD discharges. CONCLUSIONS: 1. ICD implantation in
      children is effective in the prevention of SCD. 2. In our population, the most
      frequent indications for device implantation were life-threatening ventricular
      arrhythmias occurring in patients with cardiomyopathy. 3. Cardiac arrest due to
      ventricular fibrillation may occur in children without a history of aborted SCD.
      4. ICD implantation in children is feasible and safe.

PMID- 15156220
TI  - [Transthoracic Doppler echocardiography for the non-invasive assessment of
      coronary flow reserve--a case report].
AB  - We describe a case of a 55-year-old male with anterior myocardial infarction,
      treated in the acute phase with thrombolysis. Transthoracic echocardiography
      showed hypokinetic apical segments, ejection fraction of 55% and reduced coronary
      flow reserve in the left anterior descending (LAD) coronary artery. Elective
      coronary angiography revealed a borderline (40-50%) lesion in LAD. The patient
      underwent successful angioplasty of LAD with stent implantation. Non-invasive
      coronary flow reserve measurements were repeated 3 days, 6 weeks and 6 months
      after angioplasty showing continuous improvement in this parameter. The role of
      non-invasive echocardiographic assessment of coronary flow reserve in the
      selection for angioplasty and monitoring of the effects of treatment is
      discussed.

PMID- 15156221
TI  - [Acute myocardial infarction in a patient with normal coronary arteries--a case
      report].
AB  - A case of a 72-year-old female who was admitted for elective dual-chamber
      pacemaker implantation, is presented. A few hours after the procedure the patient
      developed chest pain with ST-segment elevation in ECG and a significant increase
      in the troponin I level. An acute myocardial infarction was diagnosed. Urgent
      coronary angiography revealed normal coronary arteries without spasm. Possible
      causes of acute myocardial infarction following pacemaker implantation are
      discussed.

PMID- 15156222
TI  - [Intracoronary thrombolysis combined with platelet receptor IIb/IIIa inhibitor
      and followed by percutaneous coronary intervention for the treatment of acute
      myocardial infarction: two case reports].
AB  - By using classical thrombolytic treatment in acute myocardial infarction,
      reperfusion can be obtained in 60-80% of patients. However, in only 30-55% of
      cases TIMI grade 3 flow is achieved. Primary percutaneous coronary intervention
      (PCI) offers the potential for a higher rate of reperfusion and a lower rate of
      bleeding events. Recently, advances in platelet inhibition and PCI procedures
      have led to the combination of all the approaches. Facilitated PCI or the use of
      elective PCI after pharmacological reperfusion therapy can combine the best
      aspects of thrombolysis and mechanical revascularization in acute myocardial
      infarction. We report two cases with acute myocardial infarction successfully
      treated with PCI following thrombolytic treatment combined with platelet receptor
      IIb/IIIa inhibitor.

PMID- 15156223
TI  - [A giant left atrial myxoma as a cause of a low cardiac output syndrome: a case
      report].
AB  - A case of a 75-year-old female with a giant left atrial myxoma (54 x 42 mm in
      transthoracic echocardiography) is presented. She remained in a stable condition,
      however, developed a low cardiac output syndrome shortly after echocardiographic
      examination. This was caused by tumour displacement from the atrial wall into the
      left ventricle. The patient underwent urgent surgery during which the tumour was
      successfully removed. Histopathological examination confirmed the diagnosis of
      myxoma. Six months after surgery the patient is doing well.

PMID- 15156224
TI  - [Effects of thrombolytic therapy and coronary angioplasty on left ventricular
      remodeling after myocardial infarction].

PMID- 15156227
TI  - [Angiogram of the month].

PMID- 15156225
TI  - [Heart failure--challenge of the 21st century. Need for introducing a new model
      of the health-care system].

PMID- 15156228
TI  - [Electrocardiogram of the month].

PMID- 15156229
TI  - [Dissection of main pulmonary trunk diagnosed in a 23-year-old male].

PMID- 15156230
TI  - [Pharmacogenetics--new perspectives in the treatment of cardiovascular diseases].

PMID- 15156232
TI  - Preventing Delirium at the End of Life: Lessons From Recent Research.
AB  - Preservation of the ability to think clearly, in comfort, is a goal of end-of
      life care. Recent research on delirium at the end of life suggests clinical
      strategies for prevention of cognitive impairment. Clinicians should consider
      early warnings of mild delirium such as impairment in attention and short-term
      memory by following the patient's ability to remember 3 words or to attend to
      digit span before the patient is disoriented. If cognitive impairment is noted,
      clinicians should pay attention to reversible causes. This article reviews
      clinical concerns about opiates, benzodiazepines, steroids, hepatic
      encephalopathy, timely use of neuroleptic medications, and caretaking strategies
      at home.

PMID- 15156233
TI  - Stereochemistry in Drug Action.
AB  - The importance of stereochemistry in drug action is gaining greater attention in
      medical practice, and a basic knowledge of the subject will be necessary for
      clinicians to make informed decisions regarding the use of single-enantiomer
      drugs. Many of the drugs currently used in psychiatric practice are mixtures of
      enantiomers. For some therapeutics, single-enantiomer formulations can provide
      greater selectivities for their biological targets, improved therapeutic indices,
      and/or better pharmacokinetics than a mixture of enantiomers. This article
      reviews the nomenclature for describing stereochemistry and enantiomers,
      emphasizes the potential biological and pharmacologic differences between the 2
      enantiomers of a drug, and highlights the clinical experience with single
      enantiomers of the selective serotonin reuptake inhibitors fluoxetine and
      citalopram. In some cases, both a mixture of enantiomers and a single-enantiomer
      formulation of a drug will be available simultaneously. In these cases,
      familiarity with stereochemistry and its pharmacologic implications will aid the
      practicing physician to provide optimal pharmacotherapy to his or her patients.

PMID- 15156234
TI  - Chronic Sleep Disruption and the Reexperiencing Cluster of Posttraumatic Stress
      Disorder Symptoms Are Improved by Olanzapine: Brief Review of the Literature and
      a Case-Based Series.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is one of the most prevalent
      psychiatric disorders in young adults. Early diagnosis and treatment of PTSD are
      essential to avoid possible long-term neuropsychiatric changes in brain
      physiology and function. A cardinal symptom of PTSD is chronic sleep disruption,
      often with recurring nightmares. If untreated, PTSD symptoms often contribute to
      substance abuse and the development of other comorbid psychiatric disorders. Once
      PTSD is diagnosed, drug treatment should begin with antidepressant therapy. If
      antidepressants do not correct the sleep disruption, adjunctive treatment with
      the atypical antipsychotic olanzapine or other agents should be considered.
      METHOD: This case series reviews 7 cases of patients with PTSD (DSM-IV criteria)
      seen in primary care clinics who were successfully treated with olanzapine. In
      most cases, olanzapine therapy was adjunctive and followed failed treatment with
      antidepressant monotherapy for sleep disturbances. RESULTS: All patients reported
      improved sleep with decreased or absent nightmares, as well as improvements in
      other PTSD symptom clusters. CONCLUSION: Further controlled studies are needed to
      better characterize and validate this therapeutic indication.

PMID- 15156235
TI  - Benefits of an Outpatient Psychiatric TeleConsultation Unit: Results of a 1-Year
      Pilot.
AB  - BACKGROUND: A Psychiatric TeleConsultation Unit (PTCU) was created at the
      Massachusetts General Hospital (MGH) in response to critical changes in the
      health care delivery system. The PTCU's design was based on an understanding of
      the needs of primary care physicians (PCPs) at MGH, as derived from PCPs'
      responses to a survey and at focus groups. The PTCU was designed to supply
      psychiatric expertise to PCPs on a "1 phone call away" basis and to assist the
      MGH in supporting an increasingly large network of PCPs by expanding access to
      the MGH's psychiatric staff and services. METHOD: Open Monday through Friday, 9
      a.m. to 5 p.m., the PTCU provided PCPs with immediate telephone access to a staff
      psychiatrist who answered diagnostic- and treatment-related questions, often
      while the patient was still in the PCP's office. If a referral for mental health
      services was required, the PTCU facilitated this using an electronic mail (e
      mail)-based referral system. Data were gathered from April 1996 to April 1997.
      RESULTS: During its first year of operation, the PTCU served 107 PCPs and their
      46,377 patients; its projected capacity was 470,000 patients. It provided 595
      teleconsultations; half were primarily directed toward making a referral, one
      fourth were primarily directed toward diagnosis or treatment, and one fourth were
      for both referral- and diagnosis- or treatment-related reasons. 361 patients were
      referred via e-mail distribution lists to a network of 92 clinicians. In 72
      teleconsultations (12%), referral for mental health services was prevented. The
      estimated savings from these prevented services far exceeded the PTCU's costs of
      providing all 595 teleconsultations. Projected yearly savings for the PTCU at
      full capacity were projected at $379,080, from prevented referrals for mental
      health services. Follow-up semistructured interviews of the first 81 PCP callers
      revealed that 71% were "extremely satisfied," 18% were "very satisfied," and only
      2% were "not at all satisfied" with the PTCU. PCPs reported that the PTCU saved
      them time in 85% of teleconsultations. Teleconsultations related to diagnosis or
      treatment changed the PCP's diagnosis 20% of the time and changed the PCP's
      treatment plan in nearly two thirds of cases. Twenty percent of the
      teleconsultations were done while the patient was in the PCP's office. Ninety
      four percent of the PCPs enthusiastically said they would use the PTCU again.
      CONCLUSION: Our PTCU increased the efficiency and efficacy of care provided by
      PCPs. Cost savings associated with a reduced frequency of unnecessary referrals
      were more than the costs of the PTCU in a capitated health care system.

PMID- 15156237
TI  - Biweekly Cognitive Therapy for Social Phobia.

PMID- 15156238
TI  - Daughter Dearest?

PMID- 15156236
TI  - Poststroke Neuropsychiatric Symptoms and Pseudoseizures: A Discussion.
AB  - LESSONS LEARNED AT THE INTERFACE OF MEDICINE AND PSYCHIATRY: The Psychiatric
      Consultation Service at Massachusetts General Hospital (MGH) sees medical and
      surgical inpatients with comorbid psychiatric symptoms and conditions. Such
      consultations require the integration of medical and psychiatric knowledge.
      During their thrice-weekly rounds, Dr. Huffman and Dr. Stern discuss the
      diagnosis and management of conditions confronted. These discussions have given
      rise to rounds reports that will prove useful for clinicians practicing at the
      interface of medicine and psychiatry.

PMID- 15156239
TI  - Panic Attacks During Escalation of Mirtazapine.

PMID- 15156240
TI  - Five Years Old and Growing.

PMID- 15156241
TI  - Metabolic Issues With Atypical Antipsychotics in Primary Care: Dispelling the
      Myths.
AB  - BACKGROUND: Recently, much attention has been focused on the increased rate of
      metabolic syndrome componen ts among psychiatric patients, including glucose
      intolerance, hyperglycemia, diabetes mellitus, hyperlipidemia, hypertension, and
      weight gain. Various reports have identified cases of newly diagnosed diabetes
      during treatment with atypical antipsychotic agents. However, the question
      remains whether there is a relationship between atypical antipsychotic use and
      the metabolic syndrome or whether there is a higher risk in this population
      irrespective of medication use. METHOD: Many articles on antipsychotics and
      metabolic issues are reviews of case reports or small, cross-sectional laboratory
      studies highlighting the suspected potential for differing rates of new-onset
      diabetes cases. We conducted a retrospective review of the literature from 1998
      through 2002, using the MEDLINE database, and recent studies presented at major
      psychiatric medical conferences to create a broader perspective on the metabolic
      issues. RESULTS: We identified over 70 abstracts and published manuscripts,
      including case reports; cross-sectional lab studies; retrospective analyses of
      head-to-head, controlled clinical studies; retrospective database studies;
      pharmacoepidemiology studies; and prospective head-to-head studies presented in
      the past 4 years. Studies assessed differences in fasting plasma glucose, oral
      glucose tolerance tests (OGTT), modified OGTT, frequently sampled intravenous
      glucose tolerance tests, homeostasis model assessment-insulin resistance, odds or
      hazard ratios, prevalence, and incidence, as well as other elements of the
      metabolic syndrome. CONCLUSION: Data from this large body of scientific evidence
      indicate that the psychiatric patient population may be at a higher risk for the
      development of obesity, glucose homeostasis dysregulation, and hyperlipidemia
      compared with the general population. The available data do not demonstrate a
      consistent or clinically significant difference in the risk of new-onset diabetes
      during treatment with the various atypical antipsychotic agents.

PMID- 15156242
TI  - Patient-Physician Relationship and Service Utilization: Preliminary Findings.
AB  - BACKGROUND: Difficult physician-patient encounters pose a challenge in all
      aspects of health care. Characteristics of both physicians and patients affect
      the office encounter and utilization of services. The objectives of this study
      were to explore the impact of patients' characteristics and the patient-physician
      relationship on service utilization. METHOD: A sample of 22 family practice
      patients and their physicians completed questionnaires prior to and/or after an
      office visit. Chart review yielded demographic information and history. The
      number of office visits and phone calls were obtained from billing records.
      RESULTS: The number of patient-reported physical problems was correlated with
      negative affect (r = 0.63, p <.002), the number of phone calls to the office (r =
      0.52, p <.02), and the difficulty of the encounter as perceived by the physician
      (r = 0.58, p <.005). The number of phone calls also correlated with the number of
      life events (r = 0.43, p <.05) and the patient's perception of the physician's
      warmth (r = 0.48, p <.03) and understanding (r = 0.44, p <.04). CONCLUSION: Life
      stress, negative affect, physical complaints, and the patients' perception of
      their physician impact utilization. Armed with information about patient
      characteristics prior to the office visit, the physician can increase efficiency
      and facilitate a more productive encounter.

PMID- 15156243
TI  - Duloxetine: A New Treatment for the Emotional and Physical Symptoms of
      Depression.
AB  - BACKGROUND: Depression is underdiagnosed in the primary care setting. Physical
      symptoms such as aches, pains, and gastrointestinal disturbance are frequently
      associated with major depressive disorder (MDD) and are often the presenting
      symptoms. Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine,
      may have a positive effect on physical symptoms in addition to efficacy in
      treating emotional symptoms of depression. METHOD: Efficacy was evaluated in 6
      double-blind, placebo- and/or active comparator-controlled trials of duloxetine
      for patients with MDD (DSM-IV criteria). Efficacy in depression was determined
      primarily using the 17-item Hamilton Rating Scale for Depression (HAM-D-17).
      Secondary efficacy measures included subscales of the HAM-D-17 and assessment of
      physical symptoms. Safety evaluations included adverse events, vital signs,
      laboratory analyses, and electrocardiograms. Safety was evaluated by pooling the
      data from the MDD trials and a study of duloxetine in nondepressed patients.
      RESULTS: Duloxetine demonstrated significant differences from placebo on core
      mood symptoms, physical symptoms (e.g., back pain), and global functioning as
      early as week 1 of treatment. The estimated probabilities of remission in the
      studies that demonstrated efficacy ranged from 43% to 57%. The most frequently
      observed adverse events for duloxetine-treated patients included nausea,
      dizziness, insomnia, fatigue, and somnolence. Duloxetine did not prolong
      corrected QT intervals, and the rate of sustained elevations of blood pressure
      did not differ significantly from placebo. CONCLUSION: In these studies,
      duloxetine was safe and effective in the treatment of both emotional and physical
      symptoms of MDD. Based on dose assessments, 60 mg q.d. appears to be the optimum
      starting and therapeutic dose.

PMID- 15156246
TI  - Binge Eating, Depression, and Cognitive Therapy.

PMID- 15156245
TI  - Disulfiram Use in an Elderly Man With Alcoholism and Heart Disease: A Discussion.

PMID- 15156244
TI  - Premenstrual Dysphoric Disorder: Recognition and Treatment.
AB  - Premenstrual dysphoric disorder (PMDD) represents the more severe and disabling
      end of the spectrum of premenstrual syndrome and occurs in an estimated 2% to 9%
      of menstruating women. The most frequent PMDD symptoms among women seeking
      treatment consist of anger/irritability, anxiety/tension, feeling tired or
      lethargic, mood swings, feeling sad or depressed, and increased interpersonal
      conflicts. Women who develop PMDD appear to have serotonergic dysregulation that
      may be triggered by cyclic changes in gonadal steroids. The marked increase in
      the number of well-designed placebo-controlled studies in the past decade has
      established several selective serotonin reuptake- inhibiting antidepressants as
      effective first-line treatments for this disorder. Both continuous dosing and
      intermittent luteal dosing strategies lead to rapid improvement in symptoms and
      functioning. The present article provides a brief review of current information
      on the epidemiology, clinical presentation, neurobiology, and treatment of PMDD.

PMID- 15156247
TI  - "What's That Smell?"

PMID- 15156248
TI  - Tiagabine in the Treatment of Nervios.

PMID- 15156250
TI  - Microcirculatory efficacy of topical treatment with aescin + essential
      phospholipids gel on transcutaneous PO2 in venous insufficiency.
AB  - A gel including aescin, essential phospholipids (EPL), and heparin (EG) has been
      used for many years for local treatment of venous, microcirculatory alterations
      (varicose veins, chronic venous insufficiency). Bruises, swelling,
      thrombophlebitis, and contusions are effectively treated with this compound. The
      aim of this study was the evaluation of the efficacy of the effects of an AEPL
      (aescin+EPL) gel on the microcirculation in subjects with chronic venous
      insufficiency, venous hypertension (CVH), and venous microangiopathy.
      Transcutaneous PO(2) was measured at the perimalleolar region. After 2 weeks of
      treatment, all individual values (100%) were significantly increased (p < 0.05).
      In all patients, PO(2) increased, indicating a decrease in level of venous
      microangiopathy. Considering transcutaneous skin PO(2), treatment with AEPL in
      areas of venous microangiopathy is beneficial in the prevention of ulceration and
      improves skin healing.

PMID- 15156249
TI  - Microcirculatory efficacy of topical treatment with aescin + essential
      phospholipids gel in venous insufficiency and hypertension: new clinical
      observations.
AB  - Aescin + essential phospholipids (AEPL) topical gels are used for local treatment
      of venous and microcirculatory alterations (varicose veins, chronic venous
      insufficiency). Bruises, swelling, thrombophlebitis, and contusions are
      effectively treated with AEPL. Active ingredients are escinate and essential
      phospholipids (EPL). The aim of this new study was the evaluation of the efficacy
      of the effects of AEPL gel on the microcirculation in subjects with chronic
      venous insufficiency, venous hypertension (CVH), and venous microangiopathy.
      Patients were assessed measuring skin flux with laser-Doppler flowmetry (LDF).
      After 2 weeks of local treatment, all individual values (100%) were significantly
      decreased (p < 0.05), indicating an improvement in the microcirculation. In all
      treated patients, flux decreased at least 30% (indicating a decrease in the level
      of venous microangiopathy) (p < 0.05). Considering these observations, topical
      treatment with AEPL in areas of venous microangiopathy is beneficial, can prevent
      ulceration, and improves the skin healing processes.

PMID- 15156251
TI  - Variations in plasma free radicals with topical aescin + essential phospholipids
      gel in venous hypertension: new clinical data.
AB  - The aim of this study was the evaluation of the effects of Aescin + essential
      phospholipids (AEPL) gel on plasma free radicals (PFRs). In this study, ten
      patients with venous hypertension, no ulcerations or infections, venous
      microangiopathy, and varicose veins were treated with topical AEPL applied in a
      standard protocol. AEPL was applied for 2 weeks, three times daily at the same
      skin region (perimalleolar internal region at defined distance from the medial
      malleolus and from the anterior edge of the tibia). In subjects with venous
      hypertension, PFR values were higher than 420 Carr units. After treatment, the
      values of PRF decreased to almost normal as an effect of the massage with AEPL
      gel. The decrease in value was observed in all treatment subjects. A ranking
      system indicates that the AEPL preparation is active in all subjects who have
      venous microangiopathy. The decrease in PFR value was greater than 30% in all
      treatment subjects (p < 0.05). The decrease in PFR can be considered an important
      indication of an improvement in skin perfusion, which protects the skin from
      deterioration and eventually from venous ulcerations. The evaluation of PFR is an
      important new physiologic parameter that can be associated with other noninvasive
      tests to study the microcirculation and its evolution and improvement with
      systemic or topical medical treatment.

PMID- 15156252
TI  - Efficacy of topical treatment with aescin + essential phospholipids gel in a
      microcirculatory model of venous insufficiency.
AB  - The aim of this efficacy study was to evaluate the effects of topical aescin +
      essential phospholipids gel in a histamine model of acute microangiopathy,
      comparable to microangiopathy observed in chronic venous disease.

PMID- 15156253
TI  - Efficacy of topical treatment with aescin + essential phospholipids gel in venous
      insufficiency and hypertension.
AB  - Aescin and essential phospholipids (AEPL) in a gel was used in a microcirculatory
      model to assess the effects on skin perfusion in chronic venous insufficiency and
      severe venous hypertension. The aim of this efficacy study was to evaluate the
      efficacy of an AEPL gel on the microcirculation measuring transcutaneous skin
      PO(2) and PCO(2) in subjects with chronic venous insufficiency, venous
      hypertension (CVH), and venous microangiopathy. Transcutaneous PO(2) and PCO(2)
      were measured at the internal perimalleolar region. After 2 weeks of treatment
      with AEPL, all TcPO(2) individual values were increased and all PCO(2) values
      were decreased (p < 0.05). Average values were significantly changed toward
      normal. Therefore, considering skin PO(2) and PCO(2) variations, local treatment
      with AEPL in areas of venous microangiopathy is very effective in improving skin
      perfusion and nutrition and, possibly, in preventing venous ulcerations.

PMID- 15156254
TI  - Efficacy of topical treatment with aescin + essential phospholipids gel on
      capillary fragility.
AB  - The aim of this efficacy study was to evaluate local capillary fragility with the
      vacuum suction chamber (VSC) in patients with chronic venous hypertension due to
      chronic venous disease. All included patients had important ankle edema due to
      venous hypertension because of a post-thrombotic syndrome. Severe, deep, venous
      incompetence was present. The VSC was applied onto the internal perimalleolar
      region. Negative pressure was applied for a variable period of 2, 4, 6, 8, and 10
      minutes. The negative pressure in the plastic chamber (2 cm in diameter)-as
      previously described-was 50 mm Hg. A group of ten patients (mean age 56 years; SD
      4; M:F = 5:5) were studied. The tests were repeated in steps of two tests on
      different days. Between the two tests, with the VSC applied in different skin
      areas of the perimalleolar region, an interval of at least 30 minutes was
      observed.

PMID- 15156255
TI  - Special communication: mandate for creation of a national peripheral arterial
      disease public awareness program: an opportunity to improve cardiovascular
      health.
AB  - BACKGROUND: There has been increasing recognition of the detrimental effect of
      peripheral arterial disease (PAD) on the health of Americans, and yet there is no
      common national program of public PAD education designed to diminish this effect.
      FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education
      Strategy Meeting was recently attended by representatives of 17 professional
      societies and public health associations whose missions support the prevention,
      diagnosis, treatment, and rehabilitation of vascular diseases. This Public
      Education Strategy Meeting was intended to provide the rationale and structure to
      create a national PAD public awareness campaign to diminish the health effect of
      PAD and to improve cardiovascular outcomes in the United States. This document
      (1) provides the rationale for creation of a national PAD public education
      program; (2) reviews the development and success of national hypertension,
      hypercholesterolemia, and Women's Heart Health public education programs as
      models of educational efficacy; (3) elucidates how the work of many vascular
      professionals has led to a national consensus for creation of a national PAD
      public educational program; (4) provides an overview of the National Heart, Lung,
      and Blood Institute PAD education meeting; and (5) outlines the "next steps"
      required to accomplish these goals. OUTCOME: This meeting achieved consensus that
      we share responsibility for developing accurate, unified messages to promote PAD
      awareness and improved care. Participants agreed that the creation of such
      messages should be linked to plans to disseminate them to all Americans at risk.
      A consensus was reached that such messages, when commonly created and offered to
      the public, are most likely to achieve the rewards in better health that all
      Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation
      whose mission includes public education about the prevention, diagnosis,
      treatment, and rehabilitation of PAD, will devote its resources to guide a new
      coalition in this process and to create a national PAD awareness campaign. During
      2003 and 2004, the coalition will create the organizational underpinnings and
      time line for what will undoubtedly be a multiyear effort. CONCLUSION:
      Participants of the Public Education Strategy Meeting agreed to create a broad
      coalition to develop a National PAD Public Awareness Program, with the objectives
      to develop and disseminate public education messages on PAD. A successful
      national PAD education program will contribute to creation of a broader mandate
      to improve global cardiovascular health in the United States.

PMID- 15156256
TI  - Prevention of recurrent deep venous thrombosis with sulodexide: the SanVal
      registry.
AB  - The aim of this study was to evaluate the prevention of recurrent deep vein
      thrombosis (R-DVT) with an oral antithrombotic agent (sulodexide) in moderate to
      high-risk subjects. A group of 405 patients was included into the multicenter
      registry. Both compression and an exercise program were used as well as a risk
      factors control plan. After diagnosis of DVT, patients were treated with oral
      anticoagulants for 6 months. At the end of this period a coagulation study was
      made and patients started treatment with oral sulodexide capsules for a period of
      24 months. The femoral, popliteal, tibial, and superficial veins were scanned
      with high-resolution ultrasound at inclusion;scans were repeated at 6, 12, 18,
      and 24 months. Of the 405 subjects included into the registry 178 in the control
      group (mean age 52.2; SD 11; M:F=90:88) and 189 in the treatment group (mean age
      53.2; SD 10.3; M:F=93:96) completed the analysis period of 24 months. At 6 and 12
      months the incidence of R-DVT was lower (p<0.05) in the treatment group. At 24
      months the global incidence of R-DVT was 17.9% in the control group and 7.4% in
      the sulodexide group (p<0.05), 2.42 times lower than in controls. The 2 groups
      were comparable for age and sex distribution and for the localization of the
      thrombi at inclusion. Also the 2 groups of dropouts were comparable. In the
      control group there were 32 recurrent DVTs and 24 subjects lost to follow-up
      (total of 56) of 202 included subjects (27.7%) in comparison with 28 failures (14
      recurrent DVTs and 14 lost subjects) of 203 subjects (13.8%) in the treatment
      group. This difference was statistically significant. In this analysis the
      incidence of DVT in controls was 2.07 times higher than in the treatment group
      subjects. In conclusion sulodexide was effective in reducing recurrent thrombotic
      events in high-risk subjects.

PMID- 15156257
TI  - Surveillance versus nonsurveillance for femoro-popliteal bypass grafts.
AB  - This is a study of 97 patients who underwent 106 femoropopliteal bypass grafts (9
      bilateral bypasses) for short-distance claudication and critical ischemia.
      Patients were divided into 2 groups. The first group (n=64) was followed up by
      use of duplex scans. The second group (n=42) was followed up in clinic without
      duplex surveillance. Twenty-three patients from the surveillance group developed
      stenoses of the grafts. Of these, 14 underwent successful angioplasty. A total of
      43 grafts became blocked. Graft occlusion was significantly more common in the
      nonsurveillance group (n=29) as compared to the surveillance group (n=14) after
      both 1 and 3 years of observation (p=0.001). Patients with critical ischemia
      showed a higher rate of graft occlusion than the claudicants (p=0.0075). Sixteen
      patients in the nonsurveillance group underwent above/below-knee amputation
      compared to 1 in the surveillance group. There was no significant difference in
      the mortality rate in the 2 groups. Graft surveillance helped to improve patency
      of grafts by identifying the correctable lesions.

PMID- 15156259
TI  - Plasma homocysteine level and the angiographic extent of coronary artery disease.
AB  - Recent epidemiologic studies have shown that moderately elevated plasma
      homocysteine concentrations are associated with an increased risk for the
      development of atherosclerotic cardiovascular diseases. But, it is not known
      whether moderate hyperhomocysteinemia is associated with the angiographic extent
      of atherosclerotic cardiovascular disease in patients with coronary artery
      disease (CAD). A possible relationship was investigated between admission plasma
      homocysteine level and the angiographic extent of coronary artery disease in
      patients with CAD. In this study, 156 consecutive patients presenting with
      coronary artery disease (group 1) and control group (group 2) of 35 age-matched
      persons with normal coronary angiography were enrolled. Blood samples for
      homocysteine were obtained on admission. Plasma homocysteine concentration was
      measured with high-performance liquid chromatography with fluorescence detection.
      Radiographs from coronary angiography were viewed and scored using Sullivan's
      method to assess the atherosclerotic involvement of coronary artery disease.
      There were significant elevations in homocysteine level in group 1 compared to
      group 2 (15.59 +/-5.7 micromol/L, 9.24 +/-1.50 micromol/L; respectively, p <
      0.001). All scores (demonstrated angiographic extension of CAD) correlated
      significantly with plasma homocysteine levels; however, the Sullivan's extent
      score correlated more closely (r = 0.68, p < 0.001) than both the stenosis score
      (r = 0.44, p < 0.01) and vessel score (r = 0.35, p < 0.05). Elevated homocysteine
      levels in patients with coronary artery disease correlated with the angiographic
      extent of atherosclerotic disease.

PMID- 15156260
TI  - Provocation of coronary vasospastic angina using an isoproterenol head-up tilt
      test.
AB  - The goals of this study were to determine the value of the isoproterenol (ISO)
      head-up tilt (HUT) test in detecting coronary vasospastic angina and to
      investigate the possible mechanism responsible for coronary artery spasm. The ISO
      + HUT test was performed in 16 patients with coronary artery spasm documented by
      the intracoronary ergonovine provocation test. Patients' blood pressure and heart
      rate were measured at baseline, during the ISO + HUT (phase I), and during HUT
      after discontinuation of ISO (phase II). Patients were categorized as test
      positive if they developed angina with ST-segment elevation during testing. Eight
      patients (50%) were test-positive (5 in phase I and 3 in phase II). Between the
      test-positive and test-negative groups, no significant differences were noted in
      the changes in blood pressure throughout the test. However, there were
      significant differences in the changes in heart rate from supine to 2 minutes
      after HUT under ISO infusion (-17 +/-22 vs 11 +/-25 beats/minute; p=0.035). In
      those patients with a positive result in the phase I stage, the heart rate
      decreased initially after tilt-up, and then significantly increased later (from
      85 +/-16 to 110 +/-27 beats/minute; p=0.043), when coronary vasospasm occurred.
      In those patients with a positive result in the phase II stage, coronary
      vasospasm occurred immediately after HUT, when there was an insignificant
      transient increase in heart rate from the supine to the HUT position (from 85 +/
      12 to 92 +/-11 beats/minute; p=0.109). The ISO + HUT test can provoke coronary
      vasospasm with ST-segment elevation in 50% of the patients with coronary artery
      spasm, when combined with an extensional protocol of HUT after discontinuation of
      ISO. This study suggests that the induction of coronary artery spasm during HUT
      testing is associated with a rapid elevation of sympathetic activity during
      augmented parasympathetic activity.

PMID- 15156258
TI  - Circadian variation of the efficacy of thrombolytic therapy in acute myocardial
      infarction-isn't the time ripe for cardiovascular chronotherapy?
AB  - This study was designed to assess the circadian variation of the efficacy of
      thrombolytic therapy (TT) in 163 patients with acute myocardial infarction.
      Statistical analysis of the results suggests the existence of circadian variation
      in the efficacy of thrombolytic therapy with marked early morning resistance and
      significantly better late daytime results. There is a strong relationship between
      the normal physiologic rhythms of biochemical, hemodynamic, and hematologic
      parameters, observed in patients with CAD and the circadian fluctuations of
      efficacy of TT. Obviously the efficacy of TT is influenced by more evident impact
      of chronorisk factors during the early morning hours.

PMID- 15156261
TI  - Carotid atherosclerosis is correlated with extent and severity of coronary artery
      disease evaluated by myocardial perfusion scintigraphy.
AB  - Increased intima-media thickness (IMT) in the common carotid artery (CCA)
      correlates with conventional risk factors for cardiovascular disease and is an
      independent predictor of cardiac events. However, correlation between IMT and
      degree of ischemic heart disease evaluated by coronary angiogram is weak. The
      purpose of this study was to investigate the relationship between measures of
      carotid atherosclerosis and the extent and severity of coronary artery disease
      (CAD) in 111 consecutive patients (60 men and 51 women, mean age 60 years) with
      known or suspected CAD who were investigated with adenosine-stress myocardial
      perfusion scintigraphy. Common carotid artery lumen diameter (LD) and IMT of the
      carotid bulb and distal CCA were measured with ultrasound, and CCA cross
      sectional intima-media area (CIMA) was calculated. Seventy-two of 110 patients
      (65%) had significant perfusion defects. Increasing carotid plaque occurrence
      (absence, unilateral or bilateral occurrence) correlated with more advanced CAD
      (p<0.01). The extent and severity of myocardial hypoperfusion correlated
      significantly with presence of carotid plaque (r=0.23 and 0.24 respectively,
      p<0.05), CIMA (r=0.23 and 0.22, p<0.05), and LD (r<0.26 and 0.25, p<0.01) but not
      with IMT. In contrast to CIMA, LD failed to show an independent relation to
      extent of CAD after adjustment for age, sex, and body mass index. In conclusion,
      in subjects with intermediate to high risk of ischemic heart disease, occurrence
      of carotid plaques and increased cross-sectional intimamedia area in the common
      carotid artery are the best parameters for predicting CAD expressed as myocardial
      hypoperfusion.

PMID- 15156262
TI  - Atherogenic effect of interleukin-2 and antiatherogenic effect of interleukin-2
      antibody in apo-E-deficient mice.
AB  - Growing evidence suggests that atherosclerosis is an immune-mediated inflammatory
      process and that cytokines participate as mediators in this process. Of the
      cytokines, interleukins, which are released from both immune and nonimmune cells
      of vascular wall, are found to have multiple effects. Interleukin-2 (IL-2), a
      cytokine produced by activated T-lymphocytes, has been found to further activate
      the T cells and may potentially enhance atherogenesis. Apo-E-deficient mice fed
      with atherogenic diet were injected intraperitoneally twice a week with placebo,
      IL-2, or anti-IL-2 antibody for a period of 6 weeks. Group 1 (n = 6) was injected
      with bovine serum albumin (BSA) in phosphate-buffered saline (PBS) and served as
      controls. Group 2 (n=6) was injected with 2 x 10(4) units of recombinant murine
      IL-2 (rmIL-2) per dose reconstituted with BSA in PBS. Group 3 (n=6) was injected
      with 5 microg of anti-IL-2 per dose reconstituted with BSA in PBS. Aortic
      sections were analyzed and atherosclerotic burden was quantified. Compared to
      controls, injection of IL-2 increased measures of atherosclerosis such as the
      average lesion score (10.7 +/-0.5 vs 9.3 +/-1.1, p=0.04) and the lesion size as a
      fraction of aortic area (0.51 +/-0.03 vs 0.41 +/-0.05, p=0.01). Injection of anti
      IL-2 had a profound antiatherogenic effect. It significantly reduced the average
      number of lesions per cross section (2.6 +/-0.6 vs 4.3 +/-0.6, p=0.03), the
      average lesion score (4.6 +/-1.9 vs 9.3 +/-1.1, p=0.02), the lesion
      area/circumference (0.35 +/-0.08 vs 0.62 +/-0.10, p=0.007), and the lesion
      size/aortic area (0.23 +/-0.07 vs 0.41 +/-0.05, p=0.03). These results indicate
      that IL-2 is an atherogenic cytokine in apo-E-deficient mice and anti-IL-2 is
      protective against atherosclerosis. This may have important clinical implications
      in modifying the atherosclerotic process.

PMID- 15156263
TI  - The effect of dobutamine stress on left ventricular outflow tract gradients in
      hypertensive patients with basal septal hypertrophy.
AB  - Basal septal hypertrophy (BSH), a cause of left ventricular outflow tract (LVOT)
      obstruction, is thought to occur by increased ventricular dynamics. The aim of
      the study was to evaluate the effect of pharmacologic stress on LVOT gradients in
      a group of hypertensive patients with BSH. Dobutamine stress was used in 24
      hypertensive patients (mean age 56 +/-8 years; 11 women) with BSH and 20 normal
      controls (mean age 54 +/-9 years; 7 women). Ejection fraction and myocardial
      mass, basal septal dimension, and LVOT diameter were measured with 2-dimensional
      echocardiography. LVOT velocities and transmitral velocities before and at peak
      dobutamine infusion were determined by continuous wave Doppler and pulsed
      Doppler, respectively. There were no differences in mean ejection fraction and
      myocardial mass between BSH patients (58 +/-3%, 204 +/-24 g) and normals (56 +/
      4%, 201 +/-32 g). The basal septum was thicker in patients (1.55 +/-0.2 cm) than
      in normals (1.03 +/-0.1 cm, p<0.001). Maximum LVOT velocities were similar in BSH
      (1.2 +/-0.4 m/sec) and normals (1.1 +/-0.2 m/sec) at rest. At peak stress,
      maximum LVOT velocities were higher in BSH (3.3 +/-0.6 m/sec) than normals (1.7
      +/-0.4 m/sec, p<0.001). LV rate-pressure product at peak stress was higher in BSH
      (23,326 +/-4,388) than normals (17,592 +/-2,409, p<0.001). LV isovolumetric
      relaxation time was prolonged, and the E/A ratio was decreased in the patients at
      rest (130 +/-14 msec and 0.72 +/-0.18, respectively, p<0.001). At peak stress,
      diastolic function did not significantly change in two groups. The correlations
      between LVOT velocity change by stress and mean LVOT diameter (r=-0.668, p<0.001)
      and mean BS thickness (r=0.610; p<0.001) were significant in the whole group.
      High velocities appeared on LVOT at peak pharmacologic stress in the hypertensive
      patients with BSH compared with control group. This suggests dynamic ventricular
      ejection by stress may contribute to hypertrophy of the basal segment, which is
      the closest part of septum to increased afterload.

PMID- 15156264
TI  - The electrocardiogram in large pericardial effusion: the forgotten "P" wave and
      the influence of tamponade, size, etiology, and pericardial thickness on QRS
      voltage.
AB  - There are varying reports on the electrocardiogram in pericardial effusions. Some
      correlate low QRS voltage with tamponade and the size of the effusion while
      others do not. Low voltage also appears to vary with the etiology. There are no
      reports on the influence of pericardial thickness or changes in the P voltage.
      The authors studied 43 patients with large effusions of whom 26 had tuberculosis
      and the remaining had viral/idiopathic etiology. Pericardial thickness was
      measured at chest computed tomography. They found no correlation between the low
      QRS voltage and tamponade, size of the effusion, etiology, or pericardial
      thickness. Low voltage of the P wave and T-wave changes were more frequent than
      low QRS voltage.

PMID- 15156265
TI  - Large spontaneous coronary artery dissections-a study of three cases, literature
      review, and possible therapeutic strategies.
AB  - Spontaneous coronary artery dissection is rare, but is now being increasingly
      recognized as a prominent cause of acute ischemic coronary events occurring
      usually in relatively young patients, predominantly females. The authors describe
      the clinical course of 3 patients (1 woman) in whom large spontaneous coronary
      artery dissections developed. All had diverse clinical presentations;1 presenting
      with heart failure, the second with post-myocardial infarction angina, and the
      third with syncope. The second patient underwent coronary angioplasty with
      multiple overlapping stents while in the other two, it was the considered opinion
      to continue aggressive medical therapy. The 1-year follow-up was uneventful in
      all 3 patients. The risk factors ascertained in our patients were diabetes
      mellitus, smoking, and hypertension.

PMID- 15156266
TI  - Essential thrombocythemia-related acute ST-segment elevation myocardial
      infarction. A case report and literature review.
AB  - Essential thrombocythemia is a clonal disorder of the myeloid stem cell that
      causes pathologic expansion of the megakaryocytic elements in the bone marrow,
      with a persistent increase in the platelet count. The disease is associated with
      an elevated risk of thrombosis, hemorrhage, and vasomotor symptoms. The
      presenting features of essential thrombocythemia can range from being
      asymptomatic to thrombohemorrhagic complications including acute myocardial
      infarction. Acute ST-segment elevation myocardial infarction due to left main
      trunk and ostial left anterior descending coronary artery lesions was diagnosed
      in a young 31-year-old man. Platelet count was markedly increased and essential
      thrombocythemia was also diagnosed. Because of left main disease, primary
      coronary intervention was not feasible and an emergent coronary artery bypass
      grafting was performed along with pharmacologic management of essential
      thrombocythemia. The early postoperative period was complicated by acute
      pulmonary embolism. Hydroxyurea and anagrelide were administered postoperatively,
      resulting in the decrease of platelet count. A succinct review of myocardial
      infarction in patients with essential thrombocythemia is presented, and
      therapeutic strategies in such patients are discussed.

PMID- 15156267
TI  - Buerger's disease with multisystem involvement. A case report and a review of the
      literature.
AB  - Buerger's disease is a recurrent inflammatory, nonatherosclerotic vasoocclusive
      disease, which typically affects small and medium-sized arteries, veins, and
      nerves of the upper and lower extremities. Systemic manifestations involving
      cerebral, mesenteric, and coronary arteries are exceptional. Moreover,
      multisystem involvement of 2 or more organs is extremely rare. The authors
      present a case of Buerger's disease in a patient who subsequently developed
      cerebral and bowel infarcts as well as cavernomatous transformation of the portal
      vein. Therefore, Buerger's disease, although rare, does have a chronic aggressive
      nature in some patients.

PMID- 15156268
TI  - Spontaneous arteriovenous fistula of the vertebral artery. Three case reports.
AB  - Three cases of spontaneous arteriovenous fistulas of the vertebral artery (VAF)
      are reported. In one case the only symptom was a cervical bruit; in the other two
      cases, symptoms of multiple cervical radiculopathy were also observed. Definitive
      diagnostic findings were obtained by Doppler ultrasonography, computed
      tomography, magnetic resonance imaging, and angiography. Clinical signs of
      radiculopathy disappeared after endovascular balloon occlusion of the fistula, in
      about 1 month. In one case the vertebral artery was occluded without clinical
      consequences.

PMID- 15156269
TI  - Regression of Achilles tendon xanthomas evaluated by CT scan after hypolipidemic
      treatment with simvastatin. A case report.
AB  - Familial hypercholesterolemia (FH) is a relatively common autosomal monogenic
      disease with dominant inheritance and threefold to fourfold increase in relative
      risk of cardiovascular death in untreated patients. For a "definitive" clinical
      diagnosis of FH the Simon Broome Register proposes the presence of tendon
      xanthomas as a key feature. However, detection of tendon xanthomas by physical
      examination is subjective and difficult to use for follow-up purposes. Several
      instrumental methods have been reported to be more sensitive than physical
      examination for the evaluation of xanthomas. The present case illustrates the
      usefulness of computed tomography (CT) to detect xanthomas in the Achilles
      tendons (XAT) and their regression in response to hypolipidemic drug treatment in
      a heterozygous FH patient. As XAT are atherosclerotic plaque-like depositions of
      lipids it is likely that their progression or regression follows the behavior of
      vascular atherosclerotic lesions.

PMID- 15156270
TI  - Paradoxical effect of prostacyclin infusion in a patient with primary pulmonary
      hypertension-a case report.
AB  - Prostacyclin treatment successfully delays the need for lung transplantation in
      many patients with progressive primary pulmonary hypertension by vasodilating
      pulmonary arteries. However, the treatment of pulmonary hypertension with
      prostacyclin may cause a paradoxical increase in pulmonary artery pressure, as
      shown in this case.

PMID- 15156271
TI  - Recurrent laryngeal nerve injury: a complication of central venous
      catheterization-a case report.
AB  - This case report highlights the emergence of new complications associated with
      old procedures as the frequency of their use increases. A 29-year-old man with
      aplastic anemia was admitted for a bone marrow transplant. Before this procedure,
      a Hickman line was inserted. This was followed by hoarseness of voice. An
      examination revealed an immobile left vocal cord. Further investigations did not
      show any cause for this complication. Therefore, the hoarseness and vocal cord
      paralysis was attributed to trauma associated with the insertion of the Hickman
      line.

PMID- 15156272
TI  - Cloning and characterization of a novel gene SRG-L expressed in late stages of
      mouse spermatogenic cells.
AB  - A cDNA expressed specifically in late stages of mouse spermatogenic cells during
      spermatogenesis was cloned by using overlapping RT-PCR and RACE. The cDNA
      contained an open reading frame (ORF) of 2625 base pairs that encoded an 874
      amino acids protein. Comparison analysis of amino acid sequence showed 91% and
      80% identity to a rat homologue XP-226242 and a monkey homologue BAB63115
      respectively. The expression of the mRNA was only observed in pachytene
      spermatocytes, round, and elongating spermatids. We named this gene as SRG-L
      (spermatogenesis related gene expressed in the late stages of spermatogenic
      cells, GenBank accession No. AY352586). The tissue-specific analysis showed that
      the SRG-L was highly expressed in spleen and testis. The results suggested that
      SRG-L might play special roles during spermatogenesis, particularly related to
      meiosis and spermiogenesis. Analysis of the amino acid sequence showed there was
      a coiled-coil region near the N-terminal region and rich phosphorylation sites,
      suggesting SRG-L might function as a transmembrane protein mediating signal
      transduction. This study also demonstrated that gene cloning by RT-PCR was
      applicable and convenient when its homologous gene was known.

PMID- 15156274
TI  - Expression and identification of mutated osteoprotegerin in culture cells and
      larvae of silkworm.
AB  - The mutated osteoprotegerin (OPG-372) gene was inserted into the baculovirus
      transfer vector pBacPAK8, and the recombinant plasmid was co-transfected with
      linearized Bm-BacPAK6 virus DNA into BmN cells, then homologous recombination
      occurred inside the cells. The recombinant virus BmNPV-OPG-372 was screened and
      identified by Southern blotting. The recombinant human OPG-372 was expressed in
      cultured cells and the larvae of silkworm by inoculation of recombinant virus.
      The expression products were run on the SDS-PAGE and their immunoreactivities
      were determined by Western blotting. It was found that a 42 kD recombinant
      protein was expressed in BmN cells and a 46 kD one in larvae respectively. The
      bioactivities of the recombinant proteins were determined by hypocalcemic effect
      assay in the mice. The results showed that the recombinant proteins had a
      significant hypocalcemic effect on mice sera.

PMID- 15156273
TI  - Introduction of foreign genes into silkworm eggs by electroporation and its
      application in transgenic vector test.
AB  - Electroporation as a methodology to introduce foreign genes into silkworm eggs
      was systematically analyzed. The foreign gene in both the newly hatched and 3rd
      instar larva DNA can be detected by PCR. The amount of foreign gene in 3rd instar
      larva DNA was about 1/1000 of that in newly hatched larva DNA. The ratio of
      foreign gene entering into silkworm eggs was voltage dependent and showed
      significant difference between the tested silkworm strains. When the piggyBac
      transposon system was applied, the effect of nuclear localization signal (NLS)
      peptide and the in vitro transcribed transposase mRNA on the transposition rate
      has been measured. Results showed that the in vitro transcribed transposase mRNA
      facilitated transposition to take place earlier and NLS could result in higher
      transposition probability and earlier transposition as well. When linearized
      vectors containing varied length of flanking homologous sequences around a
      reporter gene were introduced into silkworm eggs by electroporation, the one with
      2.6 kb total arm length gave higher G1 positive ratio than that with total arm
      length of 1.5 kb and 800 bp.

PMID- 15156275
TI  - Construction and characterization of novel staphylokinase variants with
      antiplatelet aggregation activity and reduced immunogenecity.
AB  - To develop target thrombolytic agents with fibrinolytic activity, antiplatelet
      aggregation activity and reduced immunogenicity, two staphylokinase variants
      containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced
      in E. coli JF1125 and the variants, designated DGR and RL1, were purified with
      gel filtration and ion-exchange chromatography and the purity was over 95%. The
      fibrinolytic activity and kinetic constants of the two variants were comparable
      to those of recombinant wild-type staphylokinase. Both the variants can inhibit
      the platelet aggregation at a final concentration of 2 microM. The titers of
      antibodies against variants were much lower than those against recombinant
      staphylokinase in guinea pigs, which indicated that the immunogenicity of the
      variants was greatly reduced. These results confirm that it is possible to design
      and produce a bifunctional protein that possesses fibrinolytic and antiplatelet
      aggregation activities.

PMID- 15156276
TI  - Effects of denaturation and amino acid modification on fluorescence spectrum and
      hemagglutinating activity of Hericium erinaceum Lectin.
AB  - A sialic acid-binding lectin (Hericium erinaceum lectin, HEL), isolated from
      fresh fruiting bodies of Hericium erinaceum, was treated with various temperature
      and pH to investigate its fluorescence spectra and hemagglutinating activity. It
      was found that the hemagglutinating activity of HEL was relatively steady below
      60 degrees and at pH from 6 to 11, and the change of hemagglutinating activity
      was relative to the change of hydrophobic areas where tryptophan residues
      located. In fluorescence quenching study of HEL by acrylamide and KI, it was
      indicated that nearly all the tryptophan residues of HEL located on the surface
      of the molecule, and most of them were in hydrophobic areas or negatively charged
      areas. Chemical modification of HEL proved that there were about twelve
      tryptophan residues in a HEL molecule and all of them were located on the surface
      or in the shallow groove of the molecule, and eight of them were essential for
      hemagglutinating activity; aspartic acid or glutamic acid residues were involved
      in maintaining the crucial conformation of activity center and made great
      contribution to the hemagglutinating activity of HEL, but they could not touch
      the sialic acid molecule directly; tyrosine residues also played a role in the
      hemagglutinating activity of HEL; while arginine, serine, threonine, histidine
      residues had no effect on the hemagglutinating activity of HEL.

PMID- 15156277
TI  - Identification of a novel gene SRG4 expressed at specific stages of mouse
      spermatogenesis.
AB  - Spermatogenesis is a complex process. Two spermatocytes expression sequence tags
      (ESTs) BG101130 and BG100990 were found. Their putative amino acid sequences have
      high homology with rat Spag4 (sperm antigen 4). By electrical hybridization, a
      novel cDNA encoding polypeptide of 348 amino acid residues was identified from a
      mouse testis cDNA library. The new gene was designated as SRG4 (Spermatogenesis
      related gene 4) (GenBank accession No. AY307077). Results of Northern blot and
      RTPCR revealed that SRG4 expressed specifically in mouse testis. Changes of SRG4
      expression in mouse different development stages were observed by RT-PCR. The
      SRG4 mRNA was hardly detected in 2 weeks postpartum, and expressed abundantly
      from 3 weeks later, reaching top lever at 4-5 weeks, while slightly down in aging
      mouse testis. Results of in situ hybridization showed that SRG4 gene expressed
      abundantly in spermatocytes, round spermatids. This indicated SRG4 gene may play
      an important role in mouse meiotic divisions of spermatocytes.

PMID- 15156279
TI  - Semantic search among heterogeneous biological databases based on gene ontology.
AB  - Semantic search is a key issue in integration of heterogeneous biological
      databases. In this paper, we present a methodology for implementing semantic
      search in BioDW, an integrated biological data warehouse. Two tables are
      presented: the DB2GO table to correlate Gene Ontology (GO) annotated entries from
      BioDW data sources with GO, and the semantic similarity table to record
      similarity scores derived from any pair of GO terms. Based on the two tables,
      multifarious ways for semantic search are provided and the corresponding entries
      in heterogeneous biological databases in semantic terms can be expediently
      searched.

PMID- 15156278
TI  - Tissue distribution and purification of prophenoloxidase in larvae of Asian Corn
      Borer, Ostrinia furnacalis Guenee (Lepidoptera: Pyralidae).
AB  - Using ammonium sulphate precipitation, Blue-Sepharose CL-6B, Phenyl-Sepharose CL
      4B, prophenoloxidase (PPO) was isolated and purified from hemolymph of Ostrinia
      furnacalis larvae. This zymogen was a heterodimer, and composed of two subunits
      with the relative molecular mass ranging from 66.2 kD to 97.4 kD determined by
      SDS-PAGE. Western blotting and indirect immunofluorescence test showed that PPO
      was present in integument, hemolymph plasma and cell membrane of granular
      hemocytes and oenocytoids of O. furnacalis larvae.

PMID- 15156280
TI  - The fate of mitochondria in Ibex-hirus reconstructed early embryos.
AB  - Inter-species nuclear transfer could be used to preserve North Goat (Capra ibex),
      an endangered species. We established the culture conditions for ibex-hirus
      reconstructed embryos and optimized the method for DNA extractions of a single
      cell and early cloned embryo. By using mitochondria-specific probes of ibex and
      hirus respectively we found that mitochondria of donor cells can co-exist with
      recipients in 1-cell and 2-cell stages of the reconstructed embryos but not in
      the following developmental stages.

PMID- 15156281
TI  - Effects of chronic stress and phenytoin on the long-term potentiation (LTP) in
      rat hippocampal CA1 region.
AB  - To investigate the changes of LTP in hippocampal CA1 region induced by chronic
      stress and the effect of phenytoin on them, thirty-two adult male Sprague-Dawley
      rats were randomly divided equally into four groups: control group, control
      phenytoin group, stress-saline group and stress-phenytoin group. Isolated
      hippocampal slices of rats were used to observe the changes of long-term
      potentiation (LTP) in hippocampal CA1 field using electrophysiological technique.
      Amplitude of population spike (PS) and field excitatory postsynaptic potentials
      (fEPSPs) slope were used to indicate the changes of LTP. High-frequency
      stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3 field,
      and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. The
      results showed that the LTP induction rate, the increases of PS amplitude and
      fEPSPs slope after HFS in control and stress-phenytoin groups were significantly
      greater than those in stress-saline group (P<0.05). There were no significant
      differences between control group and stressphenytoin group or between control
      and control-phenytoin groups in these indexes (P>0.05). It is suggested that
      chronic stress can damage the development of LTP in hippocampal CA1 field, while
      phenytoin can protect the LTP of stressed hippocampal slices in normal state.

PMID- 15156282
TI  - Genetic diversity of taro, Colocasia esculenta (L.) Schott, in Southeast Asia and
      the Pacific.
AB  - The genetic diversity of 255 taro (Colocasia esculenta) accessions from Vietnam,
      Thailand, Malaysia,Indonesia, the Philippines, Papua New Guinea and Vanuatu was
      studied using AFLPs. Three AFLP primer combinations generated a total of 465
      scorable amplification products. The 255 accessions were grouped according to
      their country of origin, to their ploidy level (diploid or triploid) and to their
      habitat--cultivated or wild. Gene diversity within these groups and the genetic
      distance between these groups were computed. Dendrograms were constructed using
      UPGMA cluster analysis. In each country, the gene diversity within the groups of
      wild genotypes was the highest compared to the diploid and triploid cultivars
      groups. The highest gene diversity was observed for the wild group from Thailand
      (0.19), the lowest for the diploid cultivars group from Thailand(0.007). In
      Malaysia there was hardly any difference between the gene diversity of the
      cultivars and wild groups, 0.07 and 0.08, respectively. The genetic distances
      between the diploid cultivars groups ranges from 0.02 to 0.10, with the distance
      between the diploid accessions from Thailand and Malaysia being the highest. The
      genetic distances between the wild groups range from 0.05 to 0.07. First, a
      dendrogram was constructed with only the diploids cultivars from all countries.
      The accessions formed clusters largely according to the country from which they
      originated. Two major groups of clusters were revealed, one group assembling
      accessions from Asian countries and the other assembling accessions from the
      Pacific. Surprisingly, the group of diploid cultivars from Thailand clustered
      among the Pacific countries. Secondly,a dendrogram was constructed with diploid
      cultivated,triploid cultivated and wild accessions. Again the division of the
      accessions into an Asian and a Pacific gene pool is obvious. The presence of two
      gene pools for cultivated diploid taro has major implications for the breeding
      and conservation of germplasm.

PMID- 15156284
TI  - [Diagnostics of functional bladder disorders in children].
AB  - Functional bladder disorders are one of the most frequent urinary disorders in
      children. Today, we strictly differentiate enuresis from pediatric urinary
      incontinence. In most cases, these classifications will be achieved with non
      invasive, primary diagnostic procedures. In monosymptomatic enuresis, further
      invasive examinations are not necessary. However, in pediatric urinary
      incontinence invasive diagnostic tools such as video-urodynamic studies are
      mandatory for a correct classification. Recently established guidelines on the
      diagnostic procedures for the evaluation of pediatric bladder disorders will help
      to standardize the diagnostic work-up.

PMID- 15156283
TI  - Homologues of the maize rust resistance gene Rp1-D are genetically associated
      with a major rust resistance QTL in sorghum.
AB  - As part of a comparative mapping study between sugarcane and sorghum, a sugarcane
      cDNA clone with homology to the maize Rp1-D rust resistance gene was mapped in
      sorghum. The cDNA probe hybridised to multiple loci, including one on sorghum
      linkage group (LG) E in a region where a major rust resistance QTL had been
      previously mapped. Partial sorghum Rp1-D homologues were isolated from genomic
      DNA of rust-resistant and -susceptible progeny selected from a sorghum mapping
      population. Sequencing of the Rp1-D homologues revealed five discrete sequence
      classes: three from resistant progeny and two from susceptible progeny. PCR
      primers specific to each sequence class were used to amplify products from the
      progeny and confirmed that the five sequence classes mapped to the same locus on
      LG E. Cluster analysis of these sorghum sequences and available sugarcane, maize
      and sorghum Rp1-D homologue sequences showed that the maize Rp1-D sequence and
      the partial sugarcane Rp1-D homologue were clustered with one of the sorghum
      resistant progeny sequence classes, while previously published sorghum Rp1-D
      homologue sequences clustered with the susceptible progeny sequence classes. Full
      length sequence information was obtained for one member of a resistant progeny
      sequence class ( Rp1-SO) and compared with the maize Rp1-D sequence and a
      previously identified sorghum Rp1 homologue ( Rph1-2). There was considerable
      similarity between the two sorghum sequences and less similarity between the
      sorghum and maize sequences. These results suggest a conservation of function and
      gene sequence homology at the Rp1 loci of maize and sorghum and provide a basis
      for convenient PCR-based screening tools for putative rust resistance alleles in
      sorghum.

PMID- 15156285
TI  - [New developments for the surgical treatment of shoulder problems].
AB  - Tremendous advancement has been made in the surgical treatment of the shoulder
      within the last years. Arthroscopic techniques for treatment of rotator cuff
      lesions, instability problems and biceps tendon lesions are today established
      because of significant improvement of instruments, suture materials and anchor
      techniques. The 4th generation of shoulder prosthesis systems guarantee today
      anatomical and biomechanical advantages with significant functional improvement
      for the patient.

PMID- 15156286
TI  - [Gravity valves for idiopathic normal pressure hydrocephalus. A Prospective study
      of 60 patients].
AB  - OBJECTIVE: Are hydrostatic valves superior to conventional differential pressure
      shunts in patients with normal- pressure hydrocephalus, with regard to the
      postoperative results of treatment and possible complications? METHODS: From
      September 1997 to January 2002, 60 patients with idiopathic normal-pressure
      hydrocephalus were treated by surgical implantation of a hydrostatic valve
      (Miethke dual-switch valve) at the Unfallkrankenhaus Berlin. RESULTS: One year
      after the shunt operation, the clinical picture was very good for 33% of the
      patients, good for 33%, satisfactory for 17%, and poor for 17%. At 20%, the rate
      of postoperative complications (catheter dislocations, valve infections,
      underdrainage and overdrainage) is still relatively high. The opening pressure of
      the Miethke dual-switch valve did not correlate with the postoperative results of
      treatment. CONCLUSION: According to our experience, hydrostatic Miethke dual
      switch valves are superior to conventional differential pressure shunts without
      an additional gravity unit, especially with regard to the treatment of patients
      with idiopathic normal -pressure hydrocephalus, concerning both the postoperative
      results of the treatment and the incidence of possible complications. With
      differentiated diagnosis and therapy, a clinical improvement can be achieved for
      83% of such patients.

PMID- 15156287
TI  - [Cannabinoids in multiple sclerosis. Opportunity or hazard?].
AB  - Based on patient reports, animal data, and in vitro experiments, evidence has
      emerged indicating a positive effect of cannabinoids as symptomatic treatment of
      spasticity and pain in multiple sclerosis. The recently published CAMS study was
      the first multicenter, randomized, placebo-controlled phase III trial to examine
      the efficacy of cannabinoids on symptoms related to MS. There was no treatment
      effect of cannabinoids on the primary outcome measure, a difference in the
      reduction of spasticity as assessed by the so-called Ashworth score. In contrast,
      significant effects on patient-reported spasticity and pain were documented. A
      major problem of the study was a high degree of patient unmasking in the active
      treatment group. In this review, the results of the CAMS study are discussed in
      the context of previous trials, the putative mechanism of action of cannabinoids
      and their adverse event profile.

PMID- 15156288
TI  - Chylomicron remnants and oxidised low density lipoprotein have differential
      effects on the expression of mRNA for genes involved in human macrophage foam
      cell formation.
AB  - The effects of chylomicron remnants (non-oxidised or oxidised) and oxidised low
      density lipoprotein (oxLDL) on the expression of mRNA for a wide range of genes
      believed to play a role in macrophage foam cell formation were compared using
      macrophages derived from the human monocyte cell line THP-1. Chylomicron remnant
      like particles (CMR-LPs), oxidised CMR-LPs (oxCMR-LPs) and oxLDL were incubated
      with THP-1 macrophages, and the relative abundance of mRNA transcripts for genes
      involved in lipoprotein uptake, intracellular lipid metabolism, transport and
      storage and cholesterol efflux from macrophages was determined. The results show
      that CMR-LPs and oxLDL differ markedly in their effects on the expression of mRNA
      for a number of the genes tested. OxLDL increased mRNA levels for the scavenger
      receptors CD36 (x3.2) and lectin-like oxLDL receptor 1 (x2.1), and peroxisome
      proliferator-activated receptor gamma while CMR-LPs did not. In contrast, the
      expression of mRNA for the LDL receptor-like protein was raised by CMR-LPs (x1.8)
      but not oxLDL. Furthermore, down-regulation of mRNA levels for the ATP-binding
      cassette transporter (ABC) A1 was observed with CMR-LPs (x0.6), compared to the
      up-regulation found with oxLDL (x4.4). In addition, a number of significant
      differences were found between the effects of CMR-LPs and oxCMR-LPs, with the
      oxidised particles causing a striking rise in mRNA expression for the multi-drug
      resistance 1 gene (x13.7), but otherwise showing pattern more similar to that
      seen with oxLDL. These findings provide evidence to indicate that chylomicron
      remnants cause lipid accumulation in macrophages by influencing the expression of
      genes which regulate lipid metabolism at the transcriptional level, and that the
      mechanisms involved differ in important respects from those triggered by oxLDL.

PMID- 15156289
TI  - [Botulinum toxin in otorhinolaryngology].
AB  - BACKGROUND AND OBJECTIVES: Through its anticholinergic effect, botulinum toxin is
      a suitable therapeutic option for dysfunctions of the muscular and the autonomic
      nervous system. PATIENTS/METHODS: Beside the classical indications like facial
      hyperkinesis (i.e. blepharospasm, hemifacial spasm), the treatment of complex
      dystonias (oromandibular dystonia, spasmodic dystonia, cervical dystonia),
      gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum
      toxin is an alternative treatment of tension type headache and migraine. A new
      indication of botulinum toxin application may involve the treatment of nasal
      hypersecretion through the effect on the nasal glands. RESULTS: The positive
      therapeutic effect starts a few days after treatment and lasts longer in
      disorders of the autonomic nervous system. Because of its temporally limited
      therapeutic effect, the patients need further treatment. Side-effects are rare.
      CONCLUSIONS: Botulinum toxin is an effective treatment for a variety disorders
      with different etiologies and has very few side effects.

PMID- 15156290
TI  - Improving the labial commissurae and paralabial folds with minimally invasive
      procedures: a useful method for midfacial rejuvenation.
AB  - In this retrospective study, a brief description of the folds located lateral to
      the lips' commissurae and their anatomy is followed by a method to improve or
      eliminate them with local procedures. These folds, referred to as paralabial
      folds, can be treated by either limited resection or liposuction. The method
      described in this report deals directly with these folds without resorting to
      extensive facial undermining or fasciomuscular traction. The results are natural
      and very satisfactory to both the patient and the surgeon. The scars blend nicely
      with the nasolabial lines.

PMID- 15156291
TI  - Harmonized profiloplasty using balanced angular profile analysis.
AB  - To evaluate outcomes of aesthetic facial plastic surgery objectively the authors
      developed a photogrammetric profile analysis method, which they call "balanced
      angular profile analysis" (BAPA). To develop standards and ways to determine the
      conformation of various soft tissue segments analytically, 19 mean angular values
      acquired from the photographs of 71 famous female models (53 Eastern models and
      18 Western models) were standardized to provide reference data (recommended
      aesthetic mean angles [RAMA]), which contain some of the common features and
      differences between ethnic groups and races. On the basis of the data prepared
      from angular profile analyses of these photographs, the authors apply their
      developed method in a practical way to the pre- and postoperative photographs of
      patients. By using the data provided by BAPA, the clinician can identify delicate
      profile problems correctly, perform appropriate aesthetic operations, and thus
      produce better aesthetic results. The authors' harmonized and balanced angular
      profile analysis can provide surgeons with a way of determining the
      conformational problems associated with various soft tissue segments of the face.
      It also offers aesthetic plastic surgeons reference information concerning the
      creation of an attractive face during the first patient consultation. The authors
      hope that their straightforward method of profile analysis will provide facial
      plastic surgeons with a simple tool for profile analysis and surgical planning
      designed to create an attractive face.

PMID- 15156292
TI  - Mammary compliance: an objective measurement of capsular contracture.
AB  - Capsular contracture is the most unpredictable complication after mammary
      augmentation. It presents an uncertain evolution, and is one of the most
      difficulty complications to treat. Evaluation of this condition usually was
      relegated to the surgeon's judgment, but currently there are three methods for
      measuring capsular contracture: palpation, applanation tonometry, and measure of
      mammary compliance. A prospective study was conducted to evaluate the different
      methods for managing capsular contracture. Particular attention was paid to the
      measure mammary compliance with a new device: the Anton Paar Mammacompliance
      system. This study found a good match between clinical and objective
      measurements, and also between the measure of applanation tonometry and the
      measure of mammary compliance. The Anton Paar Mammacompliance system seems to be
      effective in eliminating the descriptive part and keeping to the measurements and
      objective data. It is easily reproducible in the various check ups. It permits
      objective assessment for the measure of capsular contracture.

PMID- 15156296
TI  - An optimization study of solid-state fermentation: xanthophylls extraction from
      marigold flowers.
AB  - Marigold flowers are the main natural source of xanthophylls, and marigold
      saponified extract is used as an additive in several food and pharmaceutical
      industries. In this work, the use of a solid-state fermentation (ensilage)
      process for increasing the yield of xanthophylls extracted from fermented
      marigold flowers was examined. The process consisted of a mixed culture of three
      microorganisms (Flavobacterium IIb, Acinetobacter anitratus, and Rhizopus
      nigricans), part of the normal microbiota associated with the marigold flower.
      These microorganisms had been previously isolated, and were identified as
      relevant for the ensilage process due to their capacity to produce cellulolytic
      enzymes. Based on experimental design strategies, optimum operation values were
      determined for aeration, moisture, agitation, and marigold-to-inoculum ratio in
      the proposed solid-state fermentation equipment, leading to a xanthophylls yield
      of 17.8-g/kg dry weight. The optimum achieved represents a 65% increase with
      respect to the control. HPLC analysis indicated conservation of extracted
      oleoresin. Based on the experimental results, interactions were identified that
      could be associated with the heat and mass-transfer reactions taking place within
      the bioreactor. The insight gained allows conditions that limit growth and
      metabolic activity to be avoided.

PMID- 15156293
TI  - Anti-idiotype responses abrogate anti-CD4-induced tolerance to a tumor-specific
      antigen and promote systemic tumor immunity.
AB  - PURPOSE: Immunologic-based cancer treatment modalities represent an active area
      of investigation. Included in these strategies are passive administration of
      monoclonal antibodies which recognize tumor-associated antigens and active
      vaccination with identified tumor antigens. However, several problems associated
      with these types of treatment strategies have been identified. METHODS: In this
      report, we address certain issues by employing a murine model for experimental
      pulmonary metastasis and a tumor antigen vaccination strategy that induces
      complete tumor immunity in this system. Utilizing this model, we attempt to
      address issues related to unresponsiveness to tumor antigen immunization induced
      by passive administration of a rat monoclonal anti-CD4 and the induction of anti
      idiotype responses to a passively administered monoclonal antibody and the
      effects on the induction of tumor immunity. RESULTS: The results presented
      indicate that passive administration of rat monoclonal anti-CD4 exhibits
      immunosuppressive effects that inhibit the production of antibodies to the tumor
      antigen immunization and abolishes tumor immunity. Repeated administration of the
      rat monoclonal anti-CD4 results in an anti-idiotype response that can abrogate
      unresponsiveness to tumor antigen immunization and promote systemic tumor
      immunity. CONCLUSIONS: The data examine a number of potential problems associated
      with immunologic-based treatments for cancer. These problems include the
      potential for tolerance to the tumor antigen and establishing an
      immunocompromised state where immunization with a tumor antigen failed to
      generate tumor immunity. Approaches to eliminate tolerant T cells by targeting
      anti-CD4 via anti-idiotype responses that could be generated in vivo without CD4+
      T cells allowed for recovery of nontolerant T cells, and an antibody response to
      the tumor antigen that results in tumor immunity.

PMID- 15156298
TI  - Comparison of Doppler parameters of central versus intraparenchymal renal
      arteries in physiologically normal newborns.
AB  - BACKGROUND: Changes in renal arterial Doppler flow may identify parenchymal
      disease, but in newborns knowledge of normal physiological parameters is a
      prerequisite for correct interpretation. OBJECTIVE: To evaluate renal blood flow
      in healthy newborns by means of Doppler US. MATERIALS AND METHODS: On the fourth
      day of life we examined 100 normal term newborn infants (200 kidneys). Blood flow
      in the central renal arteries was compared with that in the intraparenchymal
      arteries. Maximum systolic velocity ( V(max)), end-diastolic velocity ( V(ed)),
      mean flow velocity ( V(mean)), resistive index (RI) and pulsatility index (PI)
      were assessed. RESULTS: All parameters were significantly higher in the central
      renal arteries than in the intraparenchymal arteries (RI 0.78+/-0.07 vs 0.62+/
      0.05, P<0.0001; PI 1.84+/-0.52 vs 1.09+/-0.18, P<0.0001). CONCLUSIONS:
      Physiological data are presented that are necessary for the correct
      interpretation of neonatal Doppler US.

PMID- 15156299
TI  - Skeletal injuries associated with sexual abuse.
AB  - BACKGROUND: Sexual abuse is often associated with physical abuse, the most common
      injuries being bruising and other soft-tissue injuries, but fractures occur in 5%
      of sexually abused children. The fractures described to date have formed part of
      the spectrum of injuries in these children and have not been specifically related
      to the abusive act. OBJECTIVE: To describe concurrent sexual abuse and fractures.
      MATERIALS AND METHODS: Three children with pelvic or femoral shaft injuries in
      association with sexual abuse. RESULTS: A 3-year-old girl with extensive soft
      tissue injuries to the arms, legs and perineum also sustained fractures of both
      pubic rami and the sacral side of the right sacro-iliac joint. A 5-month-old girl
      with an introital tear was shown to have an undisplaced left femoral shaft
      fracture. A 5-year-old girl presented with an acute abdomen and pneumoperitoneum
      due to a ruptured rectum following sexual abuse. She had old healed fractures of
      both pubic rami with disruption of the symphysis pubis. CONCLUSIONS: Although the
      finding of a perineal injury in a young child may be significant enough for the
      diagnosis of abuse, additional skeletal injuries revealed by radiography will
      assist in confirmation of that diagnosis and may be more common than hitherto
      suspected.

PMID- 15156300
TI  - Successful management of isolated ventricular inversion in an adult.
AB  - We report a case of isolated ventricular inversion in a 42-year-old woman. This
      rare congenital cardiac anomaly was corrected by an intraatrial baffle procedure.
      She also underwent left-sided double-chamber endocardial pacemaker implantation
      for postoperative tachycardia bradycardia syndrome.

PMID- 15156303
TI  - Different approaches to multivariate calibration of nonlinear sensor data.
AB  - In this study, different approaches to the multivariate calibration of the vapors
      of two refrigerants are reported. As the relationships between the time-resolved
      sensor signals and the concentrations of the analytes are nonlinear, the widely
      used partial least-squares regression (PLS) fails. Therefore, different methods
      are used, which are known to be able to deal with nonlinearities present in data.
      First, the Box-Cox transformation, which transforms the dependent variables
      nonlinearly, was applied. The second approach, the implicit nonlinear PLS
      regression, tries to account for nonlinearities by introducing squared terms of
      the independent variables to the original independent variables. The third
      approach, quadratic PLS (QPLS), uses a nonlinear quadratic inner relationship for
      the model instead of a linear relationship such as PLS. Tree algorithms are also
      used, which split a nonlinear problem into smaller subproblems, which are modeled
      using linear methods or discrete values. Finally, neural networks are applied,
      which are able to model any relationship. Different special implementations, like
      genetic algorithms with neural networks and growing neural networks, are also
      used to prevent an overfitting. Among the fast and simpler algorithms, QPLS shows
      good results. Different implementations of neural networks show excellent
      results. Among the different implementations, the most sophisticated and
      computing-intensive algorithms (growing neural networks) show the best results.
      Thus, the optimal method for the data set presented is a compromise between
      quality of calibration and complexity of the algorithm.

PMID- 15156302
TI  - No relationship between high nevirapine plasma concentration and hepatotoxicity
      in HIV-1-infected patients naive of antiretroviral treatment or switched from
      protease inhibitors.
AB  - OBJECTIVE: A prospective population pharmacokinetic study of nevirapine (NVP) was
      performed to test the relationship between hepatotoxicity and NVP trough plasma
      concentration and to identify which covariates could influence NVP
      pharmacokinetics. METHODS: All patients [77 HIV-1 (human immunodeficiency virus
      type 1)-infected patients (128 samples)] were either on first-line antiretroviral
      therapy or switched from successful therapy containing protease inhibitor.
      Population pharmacokinetic parameters were estimated by a non-linear mixed-effect
      modelling method. Hepatotoxicity was evaluated by ASAT (aspartate
      aminotransferase) plasma level. RESULTS: No correlation was found between high
      NVP trough plasma concentration and high ASAT level or the increase of ASAT level
      on NVP therapy. Age and Caucasian race were found to be significant covariates of
      NVP clearance (Cl/F). Population pharmacokinetic parameters (rate absorption
      constant=1.04 h(-1); Cl/F=3.31 h(-1); apparent volume of distribution=92 l) are
      consistent with previous studies. CONCLUSION: High NVP trough plasma
      concentrations are not correlated with hepatotoxicity in our population. NVP
      clearance is decreased in the elderly patients, suggesting a potential increase
      of NVP plasma level and the interest of therapeutic drug monitoring for this
      population.

PMID- 15156304
TI  - High incidence rate of hip fracture in Taiwan: estimated from a nationwide health
      insurance database.
AB  - The objective of this study was to describe the incidence rate of hip fracture
      from 1996 to 2000 in Taiwan, based on an inpatient database of the National
      Health Insurance Program. A total of 54,199 patients, who had a first-time
      admission for a diagnosis of hip fracture (ICD9 code 820.0 through 820.9, 820.21,
      820.22, and 820.31) on discharge from January 1996 through December 2000 and aged
      50 to 100 years, were identified and included in the study. The results showed
      that the age-specific incidence rates of hip fractures were higher with
      increasing age in both genders, in an exponential manner after 65 years of age.
      The incidence was 1.6 times higher and rose about 5 years earlier among women
      than among men. Thus in these 5 years the age-adjusted incidence rates (95%
      confidence interval) of hip fracture in Taiwan were 225 (95% CI, 188-263) per
      100,000 in men and 505 (95% CI, 423-585) per 100,000 in women (adjusted to US
      white population of 1989), as compared with US white rate of 187 in men and 535
      in women. More than half of the fractures were peritrochanteric, and the recorded
      cause in most cases was a fall on the same level, from slipping, tripping, or
      stumbling (ICD9 E885). A total of 37.8% patients had hip hemiarthroplasty, 51.2%
      had open reduction of fracture with internal fixation, and 10.5% had closed
      reduction of fracture with internal fixation. We concluded that, using the data
      from a nationwide health insurance database of Taiwan, we found a high annual
      incidence rate of hip fracture for both men and women in 5 consecutive years.
      These incidence rates were higher than other reports on Chinese populations
      reported in the past 10 years and similar to that of Western countries. With the
      rapid aging of the populations of Taiwan and other Asian countries in the years
      to come, our results clearly demonstrated the impact of osteoporosis and hip
      fracture in this region.

PMID- 15156305
TI  - Comparison of anterior cruciate ligament reconstruction in male and female
      athletes using the patellar tendon and hamstring autografts.
AB  - Despite the higher incidence of anterior cruciate ligament (ACL) injuries in
      female than in male athletes few authors have studied the effects of gender on
      the outcome of ACL reconstruction. This prospective study compared the results of
      ACL reconstruction using the patellar tendon and hamstring techniques in men and
      women. We prospectively followed 80 comparable athletes (46 males, 32 females)
      from a population of 287 patients operated on at our institution for ACL
      reconstruction using either patellar tendon or hamstring graft. There were 26
      males and 14 females in the patellar tendon group, and 22 males and 18 females in
      the hamstring group. All patients were operated on by the same surgeon within 6
      months from injury and underwent the same rehabilitation program at the same
      center. After an average of 36 months the patients were assessed by clinical
      evaluation, computerized knee laxity analysis, and isokinetic and functional
      strength tests; standard knee scores were also used. Among patellar tendon
      patients there were no significant differences between males and females
      regarding knee evaluation form, laxity, or isokinetic and functional tests.
      Females in the hamstring group had significantly greater laxity, and isokinetic
      tests at 1 year revealed a significantly higher deficit of peak torque at 60
      degrees /s in flexion and extension. We suggest further studies on the clinical
      significance of these findings particularly on their possible ramifications in
      the areas of return to sports and rehabilitation of female athletes.

PMID- 15156301
TI  - Mechanical cardiopulmonary support in children and young adults: extracorporeal
      membrane oxygenation, ventricular assist devices, and long-term support devices.

PMID- 15156306
TI  - Sleeve fracture of the superior pole of patella: a case report.
AB  - The growing patella is more vulnerable to osteochondral or avulsion fractures.
      Avulsion or sleeve fractures can occur at the superior or lower pole. Superior
      pole fractures are very rare. A case of superior pole sleeve facture of the
      patella is presented and the treatment described.

PMID- 15156307
TI  - Reliability of isokinetic ankle inversion- and eversion-strength measurement in
      neutral foot position, using the Biodex dynamometer.
AB  - This study was designed to investigate the intratester and intertester
      reliability of isokinetic ankle inversion and eversion-strength measurement in
      neutral foot position in healthy adults using the Biodex dynamometer. Twenty-five
      men and women performed five maximal concentric contractions at 60 and 180
      degrees/s angular velocities. Two physicians tested each subject. The first
      physician applied the test four times, and the second physician three times.
      Reliability of peak torque was assessed by calculating the intraclass correlation
      coefficient (ICC). At both angular velocities, inversion strength was greater
      than eversion, and when the angular velocity was increased, inversion and
      eversion strength were decreased, as tested by both physicians. The first
      measurements of inversion and eversion strength of the first physician were
      significantly lower than the other measurements (p<0.01). The intratester ICCs
      for ankle inversion in healthy young adults were highly reliable (ICC 0.92-0.96),
      and for the eversion values ranged from 0.87 to 0.94. Intertester ICCs for ankle
      inversion and eversion peak torque values demonstrated a value of 0.95.
      Isokinetic tests of ankle inversion and eversion strength at 60 and 180 degrees/s
      angular velocities in neutral foot position for healthy adults are highly
      reliable with the Biodex dynamometer.

PMID- 15156308
TI  - Phosphate addition to hemodiafiltration solutions during continuous renal
      replacement therapy.
AB  - OBJECTIVE: Hypophosphatemia often occurs during continuous renal replacement
      therapy (CRRT). The addition of phosphate to dialysate and replacement solutions
      facilitates phosphate handling, but the risk of precipitation with calcium within
      these solutions has not been addressed. DESIGN AND SETTING: Experimental study
      with a retrospective observational study in a medico-surgical intensive care
      unit. METHODS AND PATIENTS: We tested the addition of phosphate to calcium-rich
      lactate- and bicarbonate-based solutions (Hemosol LG2 and Hemosol B0) used in
      CRRT to see whether precipitation occurs. Two milliliters of potassium phosphate
      added to 5-l bags gives a physiological phosphate concentration of 1.2 mmol/l. In
      addition, calcium and phosphate homeostasis was retrospectively evaluated in 20
      consecutive CRRT patients where potassium phosphate had been added to these
      solutions. MEASUREMENTS AND RESULTS: Total and ionized calcium, phosphate, pH,
      PCO(2) and bicarbonate remained essentially unchanged 5 h after the addition of 2
      ml of potassium phosphate to 5-l Hemosol solutions. Visual inspection did not
      reveal any precipitate. Of the 20 patients studied, 14 received more than 24 h of
      phosphate supplementation to dialysate and replacement solutions. Phosphate
      remained stable throughout CRRT despite phosphate intake from nutrition in 11
      cases. No adverse event was noted on potassium, calcium, pH and bicarbonate
      homeostasis. CONCLUSIONS: The addition of phosphate to Hemosol solutions does not
      precipitate with the calcium within these solutions. This practical method
      effectively prevents hypophosphatemia in CRRT patients.

PMID- 15156309
TI  - Thrombosis and hemorrhage in heparin-induced thrombocytopenia in seriously ill
      patients.
AB  - OBJECTIVE: Heparin-induced thrombocytopenia (HIT) is the most common form of drug
      induced immune-mediated thrombocytopenia. HIT may be aggravated by life
      threatening arterial and venous thrombosis and, to a lesser extent, hemorrhagic
      complications. We investigated the incidence of thromboembolic and hemorrhagic
      complications in critically ill patients with the multiple organ dysfunction
      syndrome and HIT. DESIGN: Case-control study. SETTING: A 33-bed general intensive
      care unit in a university-affiliated teaching hospital. PATIENTS: Twenty
      consecutive patients with laboratory-proven HIT compared with 20 contemporary,
      consecutive patients without HIT. INTERVENTIONS: Unfractionated heparin or low
      molecular-weight heparin were replaced by danaparoid sodium in patients with HIT.
      MEASUREMENTS AND RESULTS: Heparin-induced thrombocytopenia was proven by a
      positive platelet aggregation test. The HIT group consisted of 14 males and 6
      females aged 65.2+/-10.8 years (mean +/- standard deviation) with APACHE II
      scores of 26.7+/-5.4. Thrombocytopenia less than 100 x 10(9)/l developed within
      6.4+/-7.0 days. In 12 patients thrombocytopenia resolved after discontinuation of
      unfractionated heparin in 8.8+/-6.4 days. Arterial and venous thromboembolic
      complications occurred more frequently in HIT patients than in non-HIT patients
      (10/20 (50%) versus 0/20 (0%); chi-square p<0.001). Hemorrhagic complications
      also occurred more frequently in HIT patients than in non-HIT patients (17/20
      (85%) versus 7/20 (35%); chi-square p=0.001). CONCLUSION: In critically ill
      patients with HIT, the incidence of thromboembolic complications and hemorrhagic
      complications was remarkably high.

PMID- 15156310
TI  - [Experience with elastic stable intramedullary nailing (ESIN) of shaft fractures
      in children].
AB  - The aim of this prospective clinical controlled trial was to investigate the
      early and midterm results of shaft fractures in children treated with elastic
      stable intramedullary nailing (ESIN). From January 1997 to December 2001, elastic
      stable intramedullary nailing was carried out on 112 children with 118 diaphyseal
      fractures. The mean age was 7.7 years. There were 51 fractures of the lower arm,
      46 femoral fractures, 14 of the lower leg, and 7 of the humerus. A total of 92
      children have been followed up for more than 12 months. The mean time of follow
      up was 38 months.The mean time of fluoroscopy was 2.2 min. Open reduction was
      necessary in 3.4 %. In children with injuries of the lower extremity, full weight
      bearing was achieved after a mean period of 9.3 days. In 1.8% of the children,
      reoperation was necessary within the first 10 days after the operation. In 3.6 %
      there was painful skin irritation due to the protruding end of a nail. No
      infection or delayed union was observed. Implant removal was done after a mean
      time of 5.6 months. There was no rotational or angular deformity of more than 5
      degrees in children with isolated fractures of the lower extremity. Mean
      lengthening of the injured leg was 2.4 mm. In three children who had fractures of
      the upper extremity, a deficit in range of motion of the adjacent joints was
      detected. The current results show that intramedullary fixation of displaced
      diaphyseal fractures in children with a flexible titanium nail is a safe,
      minimally invasive surgical technique producing excellent functional and cosmetic
      results.

PMID- 15156311
TI  - [Treatment of osteoarthritis of the knee joint. Efficacy and tolerance to
      acemetacin slow release in comparison to celecoxib].
AB  - OBJECTIVE: The aim of this trial was to compare acemetacin (ACE) with celecoxib
      (CEL) in terms of tolerability and efficacy in the treatment of osteoarthritis of
      the knee joint. METHODS: A total of 105 patients (26-64 years old) suffering from
      primary osteoarthritis (OA) of the knee were enrolled in this international,
      multicenter, randomized, double blind controlled trial. Fifty three patients were
      given ACE and 52 CEL. They were treated with either 90 mg bid of slow release ACE
      or 200 mg bid of CEL for 6 weeks. Additional gastroprotective therapy was not
      provided. Tolerability was assessed by physical examination, laboratory tests,
      vital signs and reports of side effects, as well as by patient and physician
      global assessments. Efficacy parameters comprised pain assessment by visual
      analogue scale (VAS) and ordinal scale, WOMAC, SF-36 and patient and physician
      global impressions of efficacy. In addition, acetaminophen consumption was
      recorded. RESULTS: In 21 ACE (39.6%) and 19 CEL patients (36.5%), the number of
      side effects totaled 56 (ACE n=29; CEL n=27) (ns). Mean pain reduction at week 6
      was highly significant ( P<0.0001) in both groups and amounted to 38.7 mm (+/
      20.3) in the ACE group and to 35.1 mm (+/-18.7) in the CEL group (ns). Very
      similar results were seen with respect to the other efficacy parameters.
      CONCLUSION: ACE is not inferior to CEL for the short-term treatment of knee OA in
      terms of tolerability and efficacy.

PMID- 15156312
TI  - [Guidelines on antimicrobial therapy in situations of periprosthetic THR
      infection].
AB  - Periprosthetic infection is nowadays a rare complication in artificial joint
      replacement. The infection of joint prostheses is a foreign body associated
      infection at the site of bone tissue which is difficult to treat with
      antimicrobial agents. Apart from cases with early, non-established infections,
      the surgical removal of the foreign material and radical debridement of bone and
      soft tissue is necessary. The surgical revision is performed preferentially using
      a one or two stage exchange of the prosthesis. In some cases, only the removal of
      the prosthesis is necessary. In these cases, a pseudoarthroplasty or an
      arthrodesis without definitely implanted foreign material is performed.
      Amputation is carried out if all other forms of revision have failed. All of
      these surgical procedures are accomplished by antimicrobial therapy, whether
      systemically administered and/or topically by drug delivery systems. Controlled
      studies for the comparison of one and two stage exchange procedures are not
      currently available. For the therapy of periprosthetic infection, an infectious
      disease specialist who is experienced in this area is needed in addition to an
      experienced surgical team. Thus, the therapy of these infections should be
      performed exclusively in centres of competence.

PMID- 15156313
TI  - Insulin sensitivity and secretion in normal children related to size at birth,
      postnatal growth, and plasma insulin-like growth factor-I levels.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes risk is associated with low birth weight, rapid
      weight gain during childhood, and shorter stature and lower circulating IGF-I
      levels in adults. The largest variations in growth rates occur during the first
      postnatal years. We hypothesised that early postnatal variations in height and
      weight gain and IGF-I levels may be associated with risk markers for adult
      disease. METHODS: We measured the fasting insulin sensitivity (Homeostasis model)
      and insulin secretion post-oral glucose (insulinogenic index 0-30 min) in 851
      normal 8-year-old children from a prospective birth cohort. We examined
      associations between size at birth, postnatal weight gain and circulating IGF-I
      levels with insulin sensitivity and secretion at 8 years of age. RESULTS: Fasting
      insulin sensitivity at 8 years was closely related to current BMI (r= -0.33,
      p<0.0005). Lower insulin sensitivity and higher BMI and waist circumference were
      all predicted by greater weight gain between birth to 3 years of age (all
      p<0.0005); lower birth weight was associated with reduced insulin sensitivity
      only in the highest current BMI tertile ( r=0.17, p=0.006). In contrast, lower
      insulin secretion was related to smaller size at birth ( p=0.01), independent of
      postnatal weight gain and insulin sensitivity. Lower insulin secretion was also
      independently related to shorter stature at 8 years of age relative to parental
      height ( p=0.047) and with lower plasma IGF-I levels at 5 years of age ( n=252,
      p=0.004). CONCLUSIONS/INTERPRETATION: Associations between lower birth weight and
      insulin resistance may be dependent on rapid weight gain during the early
      postnatal years. However, irrespective of postnatal weight gain, smaller size at
      birth, lower IGF-I levels and lower childhood height predicted reduced
      compensatory insulin secretion.

PMID- 15156314
TI  - Peroxisome proliferator-activated receptor gamma gene polymorphisms and
      restenosis in diabetic patients after stenting in coronary arteries.

PMID- 15156316
TI  - Herpes simplex infection in urothelial carcinoma.
AB  - Herpes simplex virus (HSV), a member of the Herpesviridae family, is a very
      common pathogen that can infect any site in the body. Urothelial carcinoma (UC)
      is a common malignancy of the urinary tract. The possibility of HSV infection in
      cases of UC has attracted little attention. In this study, we investigated the
      possible presence of HSV in UC and non-neoplastic urothelium. We examined the
      incidence of HSV infection in 100 samples of UC from 78 patients and 50 samples
      of non-neoplastic urothelium from 50 autopsy cases using immunohistochemical
      staining and amplification of DNA using polymerase chain reaction (PCR).
      Infection by HSV was detected in 39 of the 100 samples of UC (35 of 78 patients)
      using immunohistochemical staining and/or PCR analysis, in marked contrast with 1
      of 50 samples of non-neoplastic urothelium. There was no significant relationship
      between infection by HSV and anatomical site, growth pattern or depth of invasion
      of UC, but the frequency of HSV infection was significantly higher in females
      than in males. Our findings indicate that UCs become infected with HSV much more
      easily than non-neoplastic urothelium.

PMID- 15156315
TI  - 11beta-Hydroxysteroid dehydrogenase Type 1: genetic polymorphisms are associated
      with Type 2 diabetes in Pima Indians independently of obesity and expression in
      adipocyte and muscle.
AB  - AIMS/HYPOTHESIS: The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) modulates tissue-specific glucocorticoid concentrations by generating
      active cortisol. We have shown that adipose tissue 11beta-HSD1 mRNA levels were
      associated with adiposity and insulinaemia. Here we conducted further expression
      and genetic association studies in Pima Indians. METHODS: The 11beta-HSD1 mRNA
      concentrations were measured in abdominal subcutaneous adipocytes (n=61) and
      skeletal muscle tissues (n=64). Single nucleotide polymorphisms in the HSD11B1
      gene were genotyped in a larger group of full-blooded Pima Indians. RESULTS: Two
      representative SNPs (SNP1, n=706; SNP5, n=839) were associated with Type 2
      diabetes mellitus (p=0.01), although neither SNP was associated with obesity.
      Among subjects with normal glucose tolerance, SNP1 (n=127) and SNP5 (n=159) were
      associated with insulin-mediated glucose uptake rates (p=0.03 and p=0.04), and
      SNP1 was further associated with fasting, 30-min, and 2-h plasma insulin
      concentrations (p=0.002, p=0.002 and p=0.03). Adipocyte 11beta-HSD1 mRNA
      concentrations were correlated positively with adiposity and insulinaemia, and
      were additionally negatively correlated with insulin-mediated glucose uptake
      rates; nevertheless, the adipocyte 11beta-HSD1 expression did not correlate with
      genotypes of the donors. The muscle 11beta-HSD1 mRNA concentrations did not
      correlate with any anthropometric or metabolic variables.
      CONCLUSIONS/INTERPRETATION: We confirmed that adipocyte 11beta-HSD1 mRNA
      concentrations were associated with adiposity, and showed that genetic variations
      in the HSD11B1 gene were associated with Type 2 diabetes mellitus, plasma insulin
      concentrations and insulin action, independent of obesity. The variable adipose
      expression might not be a primary consequence of these HSD11B1 SNPs. Therefore,
      it is possible that the HSD11B1 gene is under tissue-specific regulation, and has
      tissue-specific consequences.

PMID- 15156317
TI  - Interobserver reproducibility of modified Gleason score in radical prostatectomy
      specimens.
AB  - The Gleason score (GS) of prostate cancer is calculated by adding primary and
      secondary Gleason grades with patterns occupying less than 5% of the tumour often
      not included despite their probable prognostic significance. A modified Gleason
      score (mGS) comprising primary and tertiary patterns of higher grade has been
      proposed, but its interobserver variability has yet to be elucidated. Slides from
      69 consecutive prostatectomy specimens were circulated among four genitourinary
      pathologists. GS and mGS were assessed, and results were compared in pairs. Mean
      weighted kappa for GS and mGS were 0.56 (range 0.52-0.66) and 0.58 (range 0.49
      0.74), respectively. The difference between GS and mGS was 0, 1 and 2 score units
      in 66%, 26% and 8%, respectively, mean 0.41 score units (range 0.24-0.51). The
      increment was greater for transition-zone tumours than for peripheral-zone
      tumours (0.63 and 0.35 score units, respectively, P=0.002). An odd mGS (5, 7 or
      9) was more often given than an odd GS (77% and 62%, respectively, P<0.001).
      Disagreement between observers greater than 1 score unit was more common with mGS
      than GS (18% and 4%, respectively, P<0.001). In conclusion, overall mean weighted
      kappa for interobserver reproducibility of mGS is at least as high as that of GS.
      However, there is a clustering of mGS in odd scores, and severe disagreement is
      more commonly observed than with GS. Training of mGS assessment would possibly
      improve agreement. Tertiary Gleason patterns need to be better defined.

PMID- 15156320
TI  - Incisional abdominal hernia: the open mesh repair.

PMID- 15156318
TI  - Enhanced susceptibility to erythrocyte "apoptosis" following phosphate depletion.
AB  - Among the sequelae of phosphate depletion is anaemia, due in part to a decreased
      life span of mature erythrocytes. Recent studies have disclosed that cellular
      stress leads to an increase of cytosolic Ca(2+) activity in erythrocytes thereby
      triggering cell shrinkage and breakdown of phosphatidylserine asymmetry of the
      cell membrane, both typical features of apoptosis. In the present experiments,
      phosphatidylserine exposure and cell size were measured by fluorescence-activated
      cell sorting (FACS) analysis of annexin binding and forward scatter,
      respectively. Erythrocytes from intact mice were compared with erythrocytes from
      mice exposed to a low-phosphate diet for 4 days. Annexin binding of freshly drawn
      erythrocytes was slightly but significantly enhanced by the low-phosphate diet.
      Furthermore, intracellular phosphate and ATP concentrations were significantly
      decreased in those erythrocytes whereas intracellular Ca(2+) activity was
      unaltered. Osmotic shock (exposure to 700 mOsm by addition of sucrose for 12 h),
      removal of Cl(-) (replaced by gluconate for 15 h) or removal of glucose (12 h)
      decreased cell volume and increased the number of annexin-binding erythrocytes.
      Interestingly, these effects were significantly larger in erythrocytes from
      phosphate-depleted animals. The experiments reveal a novel mechanism triggered by
      phosphate depletion that presumably contributes to the enhanced vulnerability and
      accelerated sequestration of erythrocytes and, thus, to anaemia.

PMID- 15156319
TI  - Diagnostic laparoscopy: indications and benefits.
AB  - BACKGROUND: The increased availability of treatment options for gastrointestinal
      cancer, necessitates precise preoperative staging. Laparoscopy can be useful for
      establishing the diagnosis and staging of cancer. However, there is an ongoing
      discussion as to whether staging laparoscopy provides additional results despite
      newly developed imaging tools. METHODS: A systematic review of relevant
      literature was undertaken. The strength of evidence was classified according to
      the North of England Evidence Based Guidelines Development Project. Medline and
      manual searches were carried out to identify all published manuscripts of
      clinical trials that dealt with staging laparoscopy. Systematic quality review of
      those publications was used to verify staging accuracy, complications and trocar
      metastases. RESULTS: Only one randomized trial was performed in gynaecological
      cancer. In cervical cancer, as a result of this study, staging laparoscopy
      remains unproven. In gastrointestinal cancer (oesophageal, gastric, pancreatic,
      liver and colorectal cancers) only prospective and retrospective observational
      studies are available with an evidence-based level of grade B. As a result of
      these trials, staging laparoscopy, in a well-defined group of patients with
      locally advanced cancer, is recommended. CONCLUSION: The effects of surgical
      staging in gynaecological cancer must be kept in mind but cannot be transferred
      to gastrointestinal cancer in general. Further studies are required to answer
      those questions.

PMID- 15156321
TI  - Residual effects of prior exercise and recovery on subsequent exercise-induced
      metabolic responses.
AB  - Data on the metabolic responses to repeated endurance exercise sessions are
      limited. Thus, the aims of this study were to examine (1) the impact of prior
      exercise on metabolic responses to a subsequent exercise session and (2) the
      effect of different recovery periods between two daily exercise sessions on
      metabolic responses to the second bout of exercise. Nine male elite athletes
      participated in four 25-h trials: one bout of exercise (ONE), two bouts of
      exercise separated by 3 h of rest and one meal (SHORT), two bouts of exercise
      separated by 6 h of rest and two meals (LONG), and a trial with no exercise
      (REST). All exercise bouts consisted of 10 min cycling at 50% followed by 65 min
      at 75% of maximal O2 uptake. Compared to no prior exercise (ONE), a previous bout
      of exercise (SHORT) was followed by higher mean O2 uptake, heart rate (HR),
      rectal temperature (TR), excess post-exercise oxygen consumption and lower
      respiratory exchange ratio (R) during and after a similar exercise session 3 h
      later. A longer rest interval between the two exercise bouts (6 h versus 3 h) and
      an additional meal resulted in a decrease in O2 uptake, HR, TR and an increase in
      R during the second bout of exercise, but no effects on post-exercise metabolism
      were found. Thus, augmented metabolic stress was observed when strenuous exercise
      was repeated after only 3 h of recovery, but this was attenuated when a longer
      recovery period including an additional meal was provided between the exercise
      sessions.

PMID- 15156323
TI  - The influence of the sterilisation process on certain thermal properties.
AB  - Surgical clothing and sheets have to meet all the requirements set in the health
      care industry regarding body comfort, absorption capacity and general recognition
      of physiological safety and sterilisation capacity. The disposable surgical gown
      market is growing and the demand will increase in all product groups and market
      sectors, where the health care industry is the most dynamic growth area. The aim
      of this study was to analyse some of the thermal properties of disposable
      surgical gowns before and after different sterilisation methods, and therefore
      the influence of the sterilisation process on their thermal comfort. The
      apparatus used to measure heat transfer properties was the Thermo Labo device
      (KES FB7) which evaluates the cool/warm sensation, thermal conductivity and
      insulation properties of the test item. The results obtained highlight the
      influence of the sterilisation process on the thermal and comfort properties.

PMID- 15156322
TI  - Centrifugation as a countermeasure during actual and simulated microgravity: a
      review.
AB  - This paper summarizes what has been learned from studies of the effects of
      artificial gravity generated by centrifugation in actual and simulated weightless
      conditions. The experience of artificial gravity during actual space flight in
      animals and humans are discussed. Studies using intermittent centrifugation
      during bed rest and water immersion, as a way to maintain orthostatic tolerance
      and exercise capacity, are reviewed; their results indicate that intermittent
      centrifugation is a potential countermeasure for maintaining the integrity of
      these physiological functions in extended space missions. These results can help
      set guidelines for future experiments aimed at validating the regimes of
      centrifugation as a countermeasure for space missions. Current and future
      research projects using artificial gravity conditions in humans are discussed.

PMID- 15156324
TI  - Dry heat loss in incubator: comparison of two premature newborn sized manikins.
AB  - Keeping premature newborns warm is crucial for their survival. Their ability to
      prevent excessive heat loss to the environment and to control their body
      temperature is limited. The risk of hypothermia is particularly important for low
      birth-weight newborns with a large body surface area in relation to their mass of
      heat-producing tissues. The present study was performed to assess the body heat
      loss difference between small and large body-size premature newborns using two
      anthropomorphic thermal manikins of premature newborns of 900 g and 1,800 g
      (respective body surface areas of 0.086 and 0.150 m2). The dry heat loss from the
      six body segments of the small manikin (S) was measured and compared with that of
      the large manikin (L). The two manikins were exposed to five different
      environmental temperatures ranging between 29 and 35 degrees C in a single
      walled, air-heated closed incubator. The magnitudes of heat loss decreased
      significantly by 20.4% between the two manikins [small manikin 110.1 (44.3) W/m2
      vs large manikin 87.6 (25.8) W/m2, mean values with one standard deviation]. The
      results obtained from the comparison of the heat loss measures from the two
      manikins confirm the fact that the heat loss increases with an increase in the
      ratio of the body surface area to body mass. The thermal manikin appears to
      provide an accurate method for the assessment of thermal conditions in neonatal
      care.

PMID- 15156325
TI  - Silica, silicosis and lung-cancer: results from a cohort study in the stone and
      quarry industry.
AB  - BACKGROUND: Workers compensated for silicosis outside the mining industry are at
      an increased risk of developing lung cancer. In the meta-analyses no data from
      Germany are involved. Furthermore, exposure data are necessary if a threshold
      value is to be assessed in order to reduce the risk for silicosis and also for
      lung cancer. METHOD: A cohort study among workers compensated for silicosis
      between 1988 and 2000 from the stone and quarry industry in Germany has been
      initiated. The cohort was followed up until the end of 2001. From all workers a
      detailed description of their jobs was assessed. RESULTS: Four hundred and forty
      workers were enrolled in the study. During the follow-up 144 workers died,
      compared with 74.35 expected cases based on the mortality rates of the general
      population from Germany, leading to a standard mortality ratio (SMR) of 1.94 (95%
      CI 1.63-2.28). Lung cancer was the cause of death in 16 cases (SMR 2.40; 95% CI
      1.37-3.90). All workers had a peak exposure above 0.15 mg/m3, the current
      threshold value. The cumulative exposure was above 2 mg/m3.years and the average
      exposure was 0.10 mg/m3 or larger. No association between the exposure and the
      risk of developing lung cancer could be observed. CONCLUSIONS: Workers from the
      stone and quarry industry compensated for silicosis are at an increased risk of
      developing lung cancer. In order to reduce that risk, the exposure has to be
      lowered, with a peak exposure below 0.15 mg/m3 and an average exposure below 0.10
      mg/m3.

PMID- 15156326
TI  - The peptide nucleic acids (PNAs): introduction to a new class of probes for
      chromosomal investigation.
AB  - Peptide nucleic acids (PNAs) are synthetic DNA mimics in which the sugar
      phosphate backbone is replaced by repeating N-(2-aminoethyl) glycine units linked
      by an amine bond and to which the nucleobases are fixed. Peptide nucleic acids
      hybridize with complementary nucleic acids with remarkably high affinity and
      specificity, essentially because of their uncharged and flexible polyamide
      backbone. The unique physicochemical properties of PNAs have led to the
      development of a large variety of biological research assays, and, over the last
      few years, PNAs have proved their powerful usefulness in genetic and cytogenetic
      diagnostic procedures. Several sensitive and robust PNA-dependent methods have
      been designed for modulating polymerase chain reactions, detecting genomic
      mutation or capturing nucleic acids. The more recent applications of PNA involve
      their use as molecular hybridization probes. Thus, the in situ detection of
      several human chromosomes has been reported in various types of tissues.

PMID- 15156328
TI  - Outpatient fibre-optic laryngoscopy for stridor in children and infants.
AB  - Many neonates are referred for a diagnosis with stridor. The gold standard
      investigation has traditionally been a rigid or direct microlaryngoscopy. This
      impacts on existing theatre schedules, demands a high level of skills from the
      paediatric anaesthetist along with the risk of exposing a neonate to a general
      anaesthetic. A bed in paediatric intensive care is often required and must be
      reserved. As laryngomalacia is the most common diagnosis and less serious than
      the investigations for infants with stridor themselves, clinicians have been
      looking to use the flexible fibre-optic laryngoscope to view the upper airway in
      awake neonatal patients. We present our experience in 66 neonatal patients
      initially managed by awake per-oral flexible fibre-optic laryngoscopy for
      stridor. We conclude that the technique is safe, straightforward and allows a
      diagnosis to be achieved in a significant number of cases. We recommend it as a
      first line investigation, reserving microlaryngoscopy for the group of patients
      in whom a diagnosis cannot be made in the outpatient clinic.

PMID- 15156327
TI  - Resolution of anaphase bridges in cancer cells.
AB  - Chromosomal instability is a key step in the generation of the cancer cell
      karyotype. An indicator of unstable chromosomes is the presence of chromatin
      bridges during anaphase. We examined in detail the fate of anaphase bridges in
      cultured oral squamous cell carcinoma cells in real-time. Surprisingly,
      chromosomes in bridges typically resolve by breaking into multiple fragments.
      Often these fragments give rise to micronuclei (MN) at the end of mitosis. The
      formation of MN is shown to have important consequences for the cell. We found
      that MN have incomplete nuclear pore complex (NPC) formation and nuclear import
      defects and the chromatin within has greatly reduced transcriptional activity.
      Thus, a major consequence of the presence of anaphase bridges is the regular
      sequestration of chromatin into genetically inert MN. This represents another
      source of ongoing genetic instability in cancer cells.

PMID- 15156329
TI  - Inguinal endometriosis.
AB  - INTRODUCTION: Extrapelvic endometriosis is a rarely seen condition and it is
      occasionally presented to the general surgeons. It is often diagnosed
      incidentally. CASE REPORT: In this report we presented three cases of inguinal
      endometriosis all of which were thought to be inguinal hernia preoperatively.
      They were diagnosed during the operation for inguinal hernia repair and treated
      with simple excision of the lesions with a part of the round ligament.

PMID- 15156330
TI  - Spontaneous healing process of a supraspinatus tendon tear in rabbits.
AB  - INTRODUCTION: The rotator cuff has a characteristic structure, in that one
      surface faces articular cartilage and another faces bursa. This structure may
      produce differences in the healing process between the rotator cuff and other
      tendons. We investigated the spontaneous healing process of a surgically created
      supraspinatus tendon tear in rabbits. MATERIALS AND METHODS: A transverse, full
      thickness tear of the supraspinatus tendon was created and its healing examined.
      RESULTS: A tear of 12 mm was not repaired within 3 weeks. With a tear of 5 mm,
      reparative tissue gradually encroached into the defect from the bursal side, and
      the tear united from the bursal side to the articular side by 12 weeks. The
      healing rates (width of reparative tissue/width of the tendon x 100%) were 32.2%,
      52.4%, 58.0%, 88.9%, and 93.8% at 1, 2, 3, 6, and 12 weeks, respectively. The
      reparative tissue had continuity to the epitenon of the bursal side.
      Immunohistochemical study showed that at week 1, type III collagen was detected
      in the reparative tissue and the cutting ends, and the expression gradually
      decreased. On the other hand, the expression of type I collagen in the reparative
      tissue was weak at week 1 and increased until week 3. PCNA-positive cells were
      observed in the reparative tissue. CONCLUSION: These results show that the origin
      of the reparative tissue is the epitenon, and from the bursal side rather than
      the articular side. This model is very useful for the investigation of the
      remodeling process of an acute rotator cuff tear.

PMID- 15156331
TI  - Increased bone turnover as reflected by biochemical markers in patients with
      potentially unstable fixation of the tibial component.
AB  - INTRODUCTION: Whether biochemical markers of bone metabolism can be used in
      assessing the conditions of implant fixation is unknown. In this study, the serum
      levels of three bone markers were measured prospectively in patients undergoing
      total knee arthroplasty (TKA) to determine if patients with different fixation
      conditions of the tibial component showed any differences in the levels of the
      markers. MATERIALS AND METHODS: The fixation of the tibial component in 40 knees
      (40 patients, 14 male and 26 female, average age 71 years) was assessed by
      radiostereometric analysis (RSA), and based upon the pattern of migration,
      implants with stable fixation ( n=25) and potentially unstable fixation ( n=15)
      were identified. Serum levels of carboxyterminal propeptide of type I procollagen
      (PICP), osteocalcin (OC) and cross-linked carboxyterminal telopeptide of type I
      collagen (ICTP) were assessed and compared between the two fixation groups. Blood
      samples were obtained preoperatively (baseline) and repeated postoperatively at 1
      week, 3, 6, 12, and 24 months. RESULTS: The baseline levels of the markers were
      statistically the same ( p>0.05) between the two fixation groups.
      Postoperatively, ICTP levels in the unstable group were significantly higher than
      in the stable group from 6 to 24 months ( p=0.02). Levels of OC in the unstable
      group were higher at 12 and 24 months compared with the stable group, reaching
      statistical significance only at 12 months ( p=0.03). No difference in the levels
      of PICP was found between the two groups. CONCLUSION: The findings indicate a
      more active bone turnover probably at the bone-cement/implant interface in knees
      with potentially unstable fixation. It reveals the potential value for
      biochemical markers in monitoring implant fixation and aseptic loosening and
      suggests a possibility for improving implant fixation by drugs which inhibit
      osteolysis.

PMID- 15156332
TI  - Influence of collateral ligament laxity on patient satisfaction after total knee
      arthroplasty: a comparative bilateral study.
AB  - INTRODUCTION: Correct ligamentous balancing is an important determinant of the
      clinical outcome in total knee arthroplasty (TKA). Many surgeons prefer a tight
      rather than a lax knee during implantation of a TKA. The hypothesis in this study
      was that patients with a slightly laxer knee joint might perform better than
      patients with a tight knee joint after implantation of a TKA. PATIENTS AND
      METHODS: Twenty-two patients with bilateral knee arthroplasties were clinically
      and radiologically evaluated at a mean follow-up of 4.5 years, ranging from 2 to
      7 years. There were 12 women and 10 men with an average age of 68.9 years (range
      32-82 years) at the time of surgery. A modified HSS score (excluding laxity),
      varus and valgus stress X-rays in 30 degrees of knee flexion, and the subjective
      outcome of both knees were compared. A knee was considered tight when it opened
      less than 4 degrees and lax if it opened 4 degrees or more on stress X-ray.
      RESULTS: There was a trend towards improved range of motion and HSS score for the
      laxer knee joints. However, the difference did not achieve statistical
      significance. Eleven of the 22 patients considered one side subjectively better
      than the other side. In 10 out of these 11 TKA, the slacker knee joint was the
      preferred side ( p<0.05). CONCLUSIONS: As the present study compared bilateral
      knee joints after TKA, the same patient could act as a control group, and subtle
      subjective differences were revealed which are not quantifiable. The results
      showed that patients with a preferred side felt significantly more comfortable on
      the laxer side, indicating that during intraoperative ligamentous tensioning,
      some varus and valgus laxity at 20-30 degrees of flexion might be preferable to
      an over-tight knee joint. Further biomechanical and prospective investigations
      will be necessary to establish the correct soft-tissue tensioning.

PMID- 15156333
TI  - Radiographic and magnetic resonance imaging findings of polylevolactic acid
      screws after rotational acetabular osteotomy.
AB  - INTRODUCTION: Biodegradable polylevolactic acid implants have become more
      commonly used for the treatment of fractures and osteotomies over the past few
      years. In the present study, the biocompatibility and degradation of
      polylevolactide screws used for rotational acetabular osteotomy were assessed on
      the basis of radiographic and MRI findings. MATERIALS AND METHODS: Forty-nine
      hips of 47 patients were analyzed for this study. The average age of the patients
      at the time of surgery was 38.0 years (range 18-62 years). The original diagnosis
      was osteoarthritis in 43 hips and osteonecrosis in 6 hips. The mean duration of
      follow-up was 2.8 years (range 1.5-5.5 years). Anteroposterior radiographs
      obtained at 1 week, 6 months, 1 year after the operation, as well as the most
      recent radiographs, were used to assess bony union, the radiolucent tract of each
      screw, and the sclerotic rim around each screw. Fifteen patients were chosen
      randomly to undergo MRI. RESULTS: Union of the osteotomized surfaces occurred in
      all patients within 6 months of surgery. Radiographs showed no osteolysis, no
      formation of bone cysts, and no displacement of the osteotomized acetabulum in
      any of the 49 hips. None of the patients was found to have any complications
      caused by problems with the biocompatibility of the implants. At the final
      postoperative examination, a central radiolucent tract and a sclerotic rim around
      the screws were seen in 34/49 hips (69%) and 23/49 hips (47%), respectively. On
      MRI findings, we were able to detect significant resorption of the screws in two
      patients after 1.2 and 1.7 years of follow-up. Though localized low-intensity
      areas on T1-weighted images and high-intensity areas on T2-weighted images were
      observed at the top of the screws in 5 patients, there was no development of
      pain, tenderness, or a sinus during the follow-up period. CONCLUSION: Although
      absorption of polylevolactic acid screws did not occur in a large majority of
      cases, rotational acetabular osteotomy appears to be a good indication for the
      use of polylevolactic acid screws.

PMID- 15156335
TI  - Congenital diaphragmatic hernia: a survey of practice in Scandinavia.
AB  - There is no consensus on the treatment of congenital diaphragmatic hernia (CDH),
      and practice seems to vary between centres. The main purpose of the present study
      was to survey current practice in Scandinavia. Thirteen paediatric surgical
      centres serving a population of about 22 million were invited, and all
      participated. One questionnaire was completed at each centre. The questionnaire
      evaluated management following prenatal diagnosis, intensive care strategies,
      operative treatment, and long-term follow-up. Survival data (1995-1998) were
      available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal
      delivery and maternal steroids were used at eight and six centres, respectively.
      All centres used high-frequency oscillation ventilation (HFOV), nitric oxide
      (NO), and surfactant comparatively often. Five centres had extracorporeal
      membrane oxygenation (ECMO) facilities, and four centres transferred ECMO
      candidates. The majority of centres (7/9) always tried HFOV before ECMO was
      instituted. Surgery was performed when the neonate was clinically stable (11/13)
      and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13).
      The repair was performed by laparotomy at all centres and most commonly with
      nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres.
      Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only
      three centres treated more than five CDH patients per year. Comparing survival in
      centres treating more than five with those treating five or fewer CDH patients
      per year, there was a tendency towards better survival in the higher-volume
      centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.

PMID- 15156336
TI  - Paediatric problems in a paediatric surgical department.
AB  - It is not unusual for paediatric surgical patients to suffer from paediatric
      diseases in addition to their surgical problems. These diseases demand further
      diagnostic procedures and pre- or postoperative therapy. The aim of this study
      was to discover how many and what kinds of additional paediatric diseases are
      seen in our paediatric surgical inpatients. We retrospectively evaluated the
      hospital charts of all inpatients for 1 year. The following data were collected:
      cause of admission, therapeutic procedure (conservative/operative), surgical
      discharge diagnosis, additional paediatric diagnoses, and transfer to other
      departments. A total number of 5,026 hospital stays for 5,840 operations in 4,300
      children was evaluated. In 38% of all hospital stays, the children had one or
      more paediatric diseases. These could be divided into two groups: acute diseases
      and chronic conditions. In the acute group, 638 children suffered from acute
      infectious diseases such as respiratory infections and enteritis/gastroenteritis.
      The most common chronic conditions were allergy, asthma, epilepsy, anaemia, and
      mental retardation. A special group of patients consists of 21% of the children
      admitted because of suspected appendicitis. These children not only had a
      significantly higher incidence of additional paediatric diseases (mostly acute
      infectious diseases), but also a higher incidence of atopic diseases compared
      with the patients admitted for other reasons. The early diagnosis and treatment
      of additional paediatric diseases is essential for the success of paediatric
      surgery. The paediatrician has a significant role in caring for surgical patients
      and assisting in the perioperative management, but the paediatric surgeon should
      also be aware of the spectrum of medical diseases.

PMID- 15156337
TI  - Russell Silver syndrome and tethered spinal cord.
AB  - CASE REPORT: We report a 20-year-old male with Russell Silver syndrome and
      tethered cord syndrome. This patient presented with non-painful scoliosis. MRI
      demonstrated a conus medullaris at the superior aspect of the L3 vertebral body.
      Axial images demonstrated no fat within the filum terminale. There was a
      horizontal sacrum. The patient had no cutaneous stigmata over the lumbosacral
      spine indicative of occult spinal dysraphism. At operation, the filum terminale
      was found to be quite large at approximately 5.0 mm in diameter. Grossly, the
      filum was found to have several large vessels both anterior and posterior to it.
      Following transection of the filum the distal cord was noted to withdraw cephalad
      indicating caudal traction. DISCUSSION: We believe this to be the first report of
      Russell Silver syndrome in conjunction with tethered cord syndrome. Following
      additional reports, Russell Silver syndrome may be added to the differential
      diagnoses for tethered cord syndrome.

PMID- 15156342
TI  - [Long-term influence of pre-, intra-, and postoperative factors on the
      intraocular pressure in combined cataract and glaucoma surgery].
AB  - PURPOSE: The aim of the study was to evaluate the long-term intraocular pressure
      (IOP)-lowering effect of combined cataract and glaucoma surgery and the influence
      of peri- and intraoperative factors upon it. METHOD: In a prospective study 300
      eyes received simultaneous phacoemulsification and covered goniotrephination at
      the same site. Intraoperative factors were monitored. Median follow-up was 24
      months (8-45). RESULTS: At the last postoperative control the mean IOP was 15.4
      mmHg (14.7 mmHg in pseudoexfoliation glaucoma, n=78). Compared to preoperative
      values 60.3% had a 20% reduction of IOP to a level below 21 mmHg without eye
      medication. There was no significant rise in IOP during the follow-up time (8th
      45th month). Of no or minimal influence (pmax=0.01) were the intraoperative
      factors, the IOP at the end of surgery, and postoperative complications (fibrin
      6%, choroidal detachment 3.3%, hypotony <7 mmHg 5.5%, and blood beneath the whole
      bleb 5%). Of significant influence were a long lasting glaucoma ( p=0.003) and
      the usage of IOP-lowering eyedrops ( p<0.0001). CONCLUSION: Combined cataract and
      glaucoma surgery is a safe alternative to single glaucoma surgery with similar
      results. Intraoperative factors have minimal influence on the IOP-lowering
      effect.

PMID- 15156343
TI  - [Optical coherence tomography in the diagnosis and follow-up of patients with
      uveitic macular edema].
AB  - BACKGROUND: Optical coherence tomography (OCT) is a relatively new, noninvasive
      method and has been well established as an effective diagnostic procedure for the
      investigation of several macular diseases. Knowledge about the efficacy of OCT in
      the diagnosis and follow-up of macular edema in uveitis patients is still
      limited. PATIENTS AND METHODS: In the first part of the study, OCT was performed
      in 22 eyes of 18 patients with anterior or intermediate uveitis who showed
      angiographic and fundoscopic evidence of macular edema. The OCT results were
      compared with the visual acuity and fundoscopic and angiographic appearance of
      macular edema. In the second part of the study, the same patients were followed
      over a period of approximately 5 months (+/-2 months) and OCT was repeated at
      different time points during treatment of uveitic macula edema. RESULTS: OCT
      investigation also showed clear evidence of macular edema in all eyes and was not
      compromised by a low or medium degree of optical haze. Furthermore, OCT
      investigation revealed marked differences in the individual degree of macular
      edema (foveal heights 168-810 microm). Diffuse macular edema ( n = 4 ) and
      different types of cystoid macular edema (several distinguished cysts n = 6,
      partially or completely confluent cysts n = 11, one marked cyst n = 1) were
      observed. During the follow-up of the patients, OCT results, visual acuity, and
      fundoscopic appearance of the macula showed a comparable behavior. In some eyes,
      a stable visual acuity was accompanied by changes of foveal edema demonstrated by
      OCT. CONCLUSION: Optical coherence tomography is a safe and highly effective
      method in the diagnosis of macular edema in uveitis associated with low or medium
      haze of the optical media. Furthermore, OCT investigation seems to be useful in
      the follow-up of uveitic macular edema under treatment.

PMID- 15156341
TI  - The circadian clock in the brain: a structural and functional comparison between
      mammals and insects.
AB  - The circadian master clocks in the brains of mammals and insects are compared in
      respect to location, organization and function. They show astonishing
      similarities. Both clocks are anatomically and functionally connected to the
      optic system and possess multiple output pathways allowing synchronization with
      the environmental light-dark cycles as well as the control of diverse endocrine,
      autonomic and behavioral functions. Both circadian master clocks are composed of
      multiple neurons, which are organized in populations with different morphology,
      physiology and neurotransmitter content and appear to subserve different
      functions. In the hamster and in the cockroach, the master clock consists of a
      core region that gets input from the eyes, and a shell region from which the
      majority of output projections originate. Communication between core and shell,
      between all other populations of clock neurons as well as between the master
      clocks of both brain hemispheres is a prerequisite of normal rhythmic function.
      Phenomena like rhythm splitting and internal desynchronization can be observed
      under constant light conditions and are caused by the "uncoupling" of the master
      clocks of both brain hemispheres.

PMID- 15156344
TI  - Fetal trauma: brain imaging in four neonates.
AB  - The purpose of this paper is to describe brain pathology in neonates after major
      traffic trauma in utero during the third trimester. Our patient cohort consisted
      of four neonates born by emergency cesarean section after car accident in the
      third trimester of pregnancy. The median gestational age ( n=4) was 36 weeks
      (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of
      cranial ultrasound ( n=4), computed tomography (CT) ( n=1) and post-mortem
      magnetic resonance imaging (MRI) ( n=1). Pathology findings were correlated with
      the imaging findings ( n=3). Cranial ultrasound demonstrated a huge
      subarachnoidal hemorrhage ( n=1), subdural hematoma ( n=1), brain edema with
      inversion of the diastolic flow ( n=1) and severe ischemic changes ( n=1). In one
      case, CT demonstrated the presence and extension of the subarachnoidal
      hemorrhage, a parietal fracture and a limited intraventricular hemorrhage.
      Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post
      mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None
      of these four children survived (three children died within 2 days and one child
      died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal
      cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic
      ischemic encephalopathy were encountered.

PMID- 15156345
TI  - Pharmacokinetics of carboplatin administered with lobradimil to pediatric
      patients with brain tumors.
AB  - PURPOSE: To determine the pharmacokinetics of adaptively dosed carboplatin when
      administered in combination with the bradykinin agonist, lobradimil (RMP-7,
      Cereport), to pediatric patients with brain tumors. METHODS: Carboplatin
      pharmacokinetic studies were performed on 21 of 25 children with primary brain
      tumors who received carboplatin and lobradimil on two consecutive days every 28
      days in a phase I dose-escalation trial of lobradimil. Carboplatin was adaptively
      dosed, based on the radioisotopic glomerular filtration rate (GFR) to achieve a
      target plasma area under the concentration vs time curve (AUC) of 3.5 mg.min/ml
      per dose x2 (2.5 mg.min/ml per dose x2 in patients with prior craniospinal
      radiation or myeloablative chemotherapy). The adaptive dosing formula was:
      carboplatin dose (mg/m2)=target AUC (mg.min/ml) x [0.93 x GFR (ml/min/m2)+15].
      Carboplatin was infused over 60 min (n=15) or 15 min (n=6). The 10-min lobradimil
      infusion (100-600 ng/kg ideal body weight) began 5 min before the end of the
      carboplatin infusion. Frequent blood samples were drawn over 24 h after the first
      dose of carboplatin/lobradimil. Ultrafilterable platinum was measured by atomic
      absorption spectroscopy, and the AUC of ultrafilterable platinum was derived
      using the linear trapezoidal rule and extrapolated to infinity. RESULTS: The
      median GFR was 65 ml/min/m2 (range 38-95 ml/min/m2) and the median carboplatin
      doses for the 2.5 and 3.5 mg min/ml target AUCs were 154 and 276 mg/m2/day (124
      235 and 179-360 mg/m2/day), respectively. The measured carboplatin AUC exceeded
      the target AUC in all 21 patients by a median of 35% (range 0.2-131%). The median
      carboplatin AUCs at the 2.5 and 3.5 mg.min/ml target AUCs were 3.4 and 4.8
      mg.min/ml (2.51-5.8 and 3.9-7.7 mg.min/ml), respectively. Carboplatin clearance
      was lower than values previously reported in children and correlated poorly with
      GFR (r2=0.14). CONCLUSIONS: Adaptive dosing of carboplatin based on GFR
      overestimated the dose required to achieve the target carboplatin AUC in
      pediatric patients with brain tumors treated with concurrent lobradimil. The
      degree to which the measured carboplatin AUC exceeded the target AUC appeared to
      be greater at higher doses of lobradimil, suggesting that the failure of the
      adaptive dosing method was related to an unexpected pharmacokinetic drug
      interaction.

PMID- 15156346
TI  - Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming
      in patients with advanced myelodysplastic syndrome and high-risk acute myeloid
      leukemia.
AB  - In an attempt to improve the complete remission (CR) rates and to prolong the
      remission duration especially in elderly patients > 50 years of age, we have used
      a combination chemotherapy of idarubicin (10 mg/m2 IV x 3 days), cytarabine
      (AraC, 100 mg/m2 CIVI x 7d), and etoposide (100 mg/m2 x 5 days) in combination
      with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1
      until absolute neutrophil count (ANC) recovery] for remission induction.
      Responding patients received two consolidation courses of idarubicin, AraC, and
      etoposide, followed by a late consolidation course of intermediate-dose AraC (600
      mg/m2 IV every 12 h x 5 days) and amsacrine (60 mg/m2 IV x 5 days). A total of
      112 patients (57 male/55 female) with a median age of 58 years (range: 22-75)
      have been entered and are evaluable for response: 19 refractory anemia with
      excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML)
      evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after
      chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR)
      rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher
      in patients < or = 60 years (68 vs 55%), mainly due to a lower early death rate
      (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall
      survival is 14.5% and median duration of relapse-free survival 8 months. After 60
      months, the probability of CR patients to still be in CR and alive is 16% (20% in
      patients < or = 60 years and 13% in patients >60 years), while the probability of
      overall survival is 12% (15% in patients < or = 60 years and 9% in patients > 60
      years). Compared to our previous trial (AML-MDS Study 01-92) which was done with
      identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML
      after MDS, or secondary AML (identical median age, age range, and distribution of
      subtypes), the CR rate in all patients, as well as CR rate, overall survival, and
      relapse-free survival in patients > 60 years have significantly been improved.
      Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly
      effective for remission induction in these high-risk patients.

PMID- 15156348
TI  - The commons in transition: agrarian and environmental change in Central and
      Eastern Europe.
AB  - This paper analyzes institutional dynamics surrounding common-pool resources in
      postsocialist Central and Eastern Europe. It is conceived in close conjunction
      with the case studies by Penov, Schleyer, and Wasilewski and Krukowski (this
      issue). The purpose of this paper is to frame the individual case inquiries,
      compare their findings, and relate those to broader agrarian and environmental
      changes in the region. The case studies report a broad shift in resource
      governance from the previously dominant legal and administrative state
      hierarchies towards markets. In addition, state power has moved from central
      towards local authorities. The waning and decentralization of state power has
      caused the emergence of significant gaps between property legislation and rights
      inpractice, which have been particularly stark in fragmented political systems.
      The discrepancy between legal texts and rights-in-practice leads to the exclusion
      of wider interests in favor of individual interests in the management of common
      pool resources, resulting in resource deterioration and dwindling resource
      stocks. Thus, the comparative assessment suggests a tentative framework for
      understanding the effects of postsocialist transformations on governance of the
      commons and environmental change in Central and Eastern Europe. Its findings
      indicate an additional dimension to the diversity and distributive conflicts
      characterizing postsocialist privatization: the distribution of various rights to
      a resource among different actors. The findings also suggest the need for
      postsocialist states to take an active role in the governance of common-pool
      resources, particularly in the enforcement of legal rights.

PMID- 15156349
TI  - Effects of fish stocking on ecosystem services: an overview and case study using
      the Stockholm Archipelago.
AB  - In this article, we focus on documented and possible effects of fish stocking in
      terms of ecosystem services. The increasing use of fish stocking between 1970 and
      2000 in the semiurban setting of Stockholm archipelago, Sweden, is used as case
      study. The objective is to analyze this management practice from an ecosystem
      perspective, accounting for both the ecological and social context of releasing
      fish. The results show that enhancements of four native species (Salmo S. trutta,
      Salmo salar, Stizostedion lucioperca, and Anguilla anguilla) have dominated over
      new introductions of one nonnative species. (Oncorhynchus mykiss). The major
      objective has been to increase fish catches for local resource users. Involved
      stakeholders include three management agencies, one hydropower company, and
      several local sport fishing associations. Documented effects focus on recapture
      and production rates. However, our analysis suggests that additional positive or
      negative effects on biodiversity, food web dynamics, mobile links, or ecological
      information may also result, with possible consequences for the long-term
      provision of food, game, and aesthetic values. We conclude that a more adaptive
      and cooperative management approach could benefit from a deeper analysis of
      where, when, and what species is released, by whom, which stakeholders that use
      the fish and those ecosystem services the fish generate, and of the role of
      formal and informal institutions for monitoring and evaluating the success of
      releasing fish.

PMID- 15156350
TI  - A watershed-scale model for predicting nonpoint pollution risk in North Carolina.
AB  - The Southeastern United States is a global center of freshwater biotic diversity,
      but much of the region's aquatic biodiversity is at risk from stream degradation.
      Nonpoint pollution sources are responsible for 70% of that degradation, and
      controlling nonpoint pollution from agriculture, urbanization, and silviculture
      is considered critical to maintaining water quality and aquatic biodiversity in
      the Southeast. We used an ecological risk assessment framework to develop
      vulnerability models that can help policymakers and natural resource managers
      understand the impact of land cover changes on water quality in North Carolina.
      Additionally, we determined which landscape characteristics are most closely
      associated with macroinvertebrate community tolerance of stream degradation, and
      therefore with lower-quality water. The results will allow managers and
      policymakers to weigh the risks of management and policy decisions to a given
      watershed or set of watersheds, including whether streamside buffer protection
      zones are ecologically effective in achieving water quality standards. Regression
      analyses revealed that landscape variables explained up to 56.3% of the
      variability in benthic macroinvertebrate index scores. The resulting
      vulnerability models indicate that North Carolina watersheds with less forest
      cover are at most risk for degraded water quality and steam habitat conditions.
      The importance of forest cover, at both the watershed and riparian zone scale, in
      predicting macrobenthic invertebrate community assemblage varies by geographic
      region of the state.

PMID- 15156351
TI  - Public water sources in rural watersheds of Nepal's Middle Mountains: issues and
      constraints.
AB  - Inadequacy and poor quality of water supply for domestic purposes is increasingly
      becoming a concern in rural catchments of the Middle Mountains of Nepal. Water
      quantity is an issue in pocket areas of these catchments, while water quality is
      subject to concern in most of the water sources. Microbiological contamination in
      particular poses a risk to human health. In addition, sediment pollution during
      the monsoon season is perceived as an issue by the local residents. Elevated
      phosphate and nitrate levels in many water sources indicate intensive interaction
      with surface water hailing from agricultural areas and human settlements. These
      water quantity and quality concerns in two watersheds of Nepal, the Jhikhu Khola
      and the Yarsha Khola watersheds, are not isolated cases. Similar problems are
      reported from other watersheds monitored under the People and Resource Dynamics
      in Mountain Watersheds of the Hindu Kush-Himalayas (PARDYP) project in China,
      India, and Pakistan and the literature of this region.

PMID- 15156352
TI  - A posteriori evaluation of strategies of management: the effectiveness of no-wash
      zones in minimizing the impacts of boat-wash on macrobenthic infauna.
AB  - Wind-driven waves are important in structuring intertidal and shallow subtidal
      assemblages of macrobenthic infauna. In the sheltered waters of estuaries, boat
      generated waves (wash) may play a similar role because they are typically of a
      similar amplitude or larger than wind-driven waves. However, few studies have
      attempted to determine the role of wash in structuring assemblages. Consequently,
      strategies for managing boating focus around minimization of bank erosion. Along
      the Parramatta River (Sydney, Australia), no-wash zones have been established and
      mangroves planted to minimize the erosion of riverbanks and collapse of seawalls
      purportedly caused by 35-m-long RiverCat ferries. Although intended to also
      reduce the ecological impacts of wash, it is unclear whether these strategies
      achieve this goal. Unvegetated and vegetated (among the pneumatophores of
      mangroves) sediments were sampled in wash and no-wash zones along the Parramatta
      River to assess the effectiveness of no-wash zones and vegetation of river banks
      in reducing the ecological impacts of wash. Specifically, it was hypothesized
      that (1) assemblages of intertidal macrobenthic infauna would differ between wash
      and no-wash zones of the Parramatta River and (2) these differences would be
      greater in unvegetated than in vegetated habitat. As predicted, assemblages of
      macrobenthic infauna differed between the wash and no-wash zones. Capitellids,
      nereids, and spionids were more abundant in the no-wash zone. Contrary to the
      hypothesis, differences were no greater in the unvegetated habitat than in the
      vegetated habitat. The results suggest an impact of wash on assemblages of
      macrobenthic infauana and a role for no-wash zones in minimizing the effects of
      this disturbance.

PMID- 15156353
TI  - Observed winter warming of the Chesapeake Bay estuary (1949-2002): implications
      for ecosystem management.
AB  - A large number of studies have documented 20th century climate variability and
      change at the global, hemispheric, and regional levels. However, understanding
      the implications of climate change for environmental management necessitates
      information at the level of the ecosystem. Historical monitoring data from the
      Chesapeake Bay estuary were used to identify temporal patterns of estuarine
      temperature anomalies in the surface (</=1 m) and subsurface (>/=15 m) between
      1949 and 2002. Data indicated a trend in surface and subsurface warming of +0.16
      degrees C and +0.21 degrees C per decade, respectively, driven by warming during
      winter and spring. These trends suggest warming of the estuary since the mid-20th
      century of approximately 0.8-1.1 degrees C. Estuarine temperatures correlated
      well with other independent data records for sea surface and surface air
      temperatures in the region and to a lesser extent, the northern hemisphere. Gross
      long-term temperature variability in the estuary was consistent with North
      Atlantic climate variability associated with the prolonged positive North
      Atlantic Oscillation/Arctic Oscillation and increased anthropogenic radiative
      forcing, although localized environmental drivers likely are important as well. A
      simple spatial analysis revealed strong seasonal latitudinal and longitudinal
      gradients in estuarine temperature as well as a north-south gradient in long-term
      temperature trends. Continued warming of the estuary will have important
      implications for ecosystem structure and function as well as attempts to manage
      existing challenges such as eutrophication and benthic hypoxia. However, such
      management efforts must be cognizant of the effects of various climate and
      nonclimate drivers of environmental variability and change operating over
      different spatial and temporal scales.

PMID- 15156354
TI  - Conflict on the coast: using geographic information systems to map potential
      environmental disputes in Matagorda Bay, Texas.
AB  - The sustainable management of coastal natural resources inevitably involves
      identifying stakeholder conflicts and developing planning processes that prevent
      these conflicts from becoming intractable disputes. This study links
      environmental conflict to specific areas within a large ecological system.
      Specifically, we use Geographic Information Systems (GIS) to map potentially
      competing stakeholder values associated with establishing protected areas in
      Matagorda Bay, Texas. By overlaying multiple values associated with a range of
      stakeholders across space, we are able to identify hotspots of potential conflict
      as well as areas of opportunity for maximizing joint gains. Mapping stakeholder
      conflict is an approach to proactively locate potential controversy in response
      to a specific environmental management proposal and guide decision makers in
      crafting planning processes that mitigate the possibility of intractable disputes
      and facilitate the implementation of sustainable coastal policies. Results
      indicate that under different management scenarios, protected area proposals will
      generate more conflict in specific areas. Most notably, regulated uses would
      produce the greatest degree of conflict on or near shore, particularly at the
      mouth of the Colorado River. Additionally, of all the management scenarios
      evaluated, the prohibition of coastal structural development would generate the
      overall highest level of conflict within the Bay. Based on the results, we
      discuss the policy implications for environmental managers and provide guidance
      for future research on location-based conflict management within the coastal
      margin.

PMID- 15156355
TI  - Editorial: Online SCAR Expert Hotline.

PMID- 15156356
TI  - iScout: an intelligent scout for accessing and navigating large image sets in a
      PACS.
AB  - A new software tool for PACS, called iScout (intelligent scout), has been
      developed and optimized for a radiology workstation. The purpose of iScout is to
      display an overview of a large image series, allowing the user to select images
      for priority downloading from a PACS server to a PACS workstation. This allows
      radiologists to reduce the delays that are associated with downloading hundreds
      or even thousands of images. Several schemes that semiautomatically manage the
      download process are presented along with tests to measure performance. The
      results of the tests confirm that priority downloading provides faster access to
      images in large image series and that the time savings increase in proportion to
      the study size.

PMID- 15156357
TI  - Activation tagging in plants: a tool for gene discovery.
AB  - A significant limitation of classical loss-of-function screens designed to
      dissect genetic pathways is that they rarely uncover genes that function
      redundantly, are compensated by alternative metabolic or regulatory circuits, or
      which have an additional role in early embryo or gametophyte development.
      Activation T-DNA tagging is one approach that has emerged in plants to help
      circumvent these potential problems. This technique utilises a T-DNA sequence
      that contains four tandem copies of the cauliflower mosaic virus (CaMV) 35S
      enhancer sequence. This element enhances the expression of neighbouring genes
      either side of the randomly integrated T-DNA tag, resulting in gain-of-function
      phenotypes. Activation tagging has identified a number of genes fundamental to
      plant development, metabolism and disease resistance in Arabidopsis. This review
      provides selected examples of these discoveries to highlight the utility of this
      technology. The recent development of activation tagging strategies for other
      model plant systems and the construction of new more sophisticated vectors for
      the generation of conditional alleles are also discussed. These recent advances
      have significantly expanded the horizons for gain-of-function genetics in plants.

PMID- 15156358
TI  - Rates of antimicrobial resistance among common bacterial pathogens causing
      respiratory, blood, urine, and skin and soft tissue infections in pediatric
      patients.
AB  - Antimicrobial resistance patterns among the principal bacterial pathogens from
      infections of the respiratory tract, blood, skin and soft tissue, and urinary
      tract of pediatric patients from the USA, Canada, Germany, France, and Italy were
      studied using the The Surveillance Network (TSN) database. Among Streptococcus
      pneumoniae isolates from respiratory tract infections, the prevalence of high
      level penicillin resistance (MIC>/=2 microg/ml) ranged from 1.1 (Italy) to 36.2%
      (USA); erythromycin resistance was higher, ranging from 13.4 (Germany) to 63.8%
      (France). The prevalence of beta-lactamase-positive Haemophilus influenzae among
      isolates from lower respiratory tract infections ranged from <10 (Italy and
      Germany) to 38.4% (USA). Among isolates from blood and skin and soft tissue
      infections, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      ranged from 7.2% (Canada and Germany) to 27.3% (Italy). The prevalence of
      Escherichia coli and Klebsiella pneumoniae with putative extended-spectrum beta
      lactamases among isolates from blood, urinary tract, and skin and soft tissue
      infections ranged from 0 (Germany and France) to 29.6% (Italy). With the
      exception of pseudomonal infections or infections with MRSA, amoxicillin
      clavulanate retained moderate activity, whilst ceftriaxone and cefepime were the
      most effective broad-spectrum injectable agents. Meropenem was the most effective
      agent against Pseudomonas aeruginosa with <5% resistance. Low levels of
      resistance, along with acceptable safety profiles and the availability of
      convenient oral formulations, continue to support the use of ceftriaxone,
      cefepime, amoxicillin-clavulanate, and meropenem as viable options for the
      treatment of infections in pediatric patients.

PMID- 15156359
TI  - Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix
      Saguenay (ARSACS) families from Turkey.
AB  - We studied five families with pediatric-onset recessive spastic ataxia from
      Turkey. The clinical characteristics and linkage studies are compatible with
      autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). SACS
      mutations are responsible for ARSACS in Quebec families. In four of the five
      families tested we detected new disease-causing mutations using automated
      sequencing of SACS. Our study raises to 12 the number of SACS mutations detected
      in ARSACS patients with origins around the Mediterranean basin.

PMID- 15156360
TI  - A strategy for treatment of type III and IV thoracoabdominal aortic aneurysm.
AB  - The aim of this study was to describe the results of resection and graft
      replacement for type III and IV thoracoabdominal aortic aneurysm repair. In this
      retrospective study, 27 patients underwent resection and graft replacement for
      type III (10) or type IV (17) thoracoabdominal aortic aneurysms. Nine patients
      had rupture, 12 were symptomatic, and 6 were operated on electively. The "clamp
      and-sew" technique was applied in six cases. In 12 patients with type IV aneurysm
      the proximal part of the vascular graft was beveled, including the orifices of
      the celiac, superior mesenteric, and one or both renal arteries in the proximal
      anastomosis. Finally, eight patients underwent surgical application of a shunt
      for perfusion of the celiac and superior mesenteric arteries. One patient was
      treated with a combination of open and endovascular surgery. There were four
      early deaths (14.8%), all following operations for rupture, which represents a
      45% mortality rate in this subgroup of patients. Two patients with type III
      aneurysm had postoperative paraparesis. One was symptomatic whereas the other was
      operated on electively. Excluding the patients with rupture, the accumulated 5
      year survival rate was 65%. These results indicate that direct cross-clamping of
      the aorta gives limited time for performing the necessary anastomoses without
      inducing mesenteric ischemia. Inclusion of the orifices of the visceral arteries
      in the upper anastomosis is a feasible method during surgery for type IV
      aneurysms. Finally, shunting of the celiac and the superior mesenteric arteries
      seems to be useful, especially during surgery for type III aneurysms.

PMID- 15156362
TI  - Sexual function and quality of life in women after elective aortic surgery.
AB  - The incidence of sexual dysfunction in women after open aortic reconstruction is
      unknown. Additionally, previous studies of quality of life (QOL) following aortic
      surgery include small numbers of women compared to those of men. The purpose of
      this study was to determine the effects of elective aortic surgery on sexual
      function (SF) and QOL in women. Two validated questionnaires, the Female Sexual
      Function Index (FSFI) and Short Form 36 (SF-36), were mailed to all women who
      underwent elective aortic reconstruction between 1995 and 2000. Comparisons were
      made between preoperative (baseline) SF, 1-year postoperative SF, and SF within
      the 4 weeks preceding receipt of the questionnaire. The SF-36 responses were
      compared to national norms. Of the 182 women who underwent elective aortic
      reconstruction, only 122 patients (67%) were alive and able to complete the
      questionnaires. Of 56 patients (46%) who had sexual partners, 21 (38%) returned
      both questionnaires and 22 patients returned only the SF-36 portion. There were
      no differences in desire, arousal, lubrication, orgasm, satisfaction, or pain
      scores. There was a trend toward poorer baseline sexual function in claudicants
      in all domains, with the pain domain reaching significance (p = 0.03). Previous
      hysterectomy did not affect sexual function (p > 0.05). Following aortic surgery,
      patients had a significant decrease in the role-physical (p = 0.03), social
      functioning (p = 0.01), role-emotional (p < 0.001), and mental health domains (p
      < 0.001) compared to national norms. There were no differences in QOL scores
      between claudicants and aneurysm patients or married and nonmarried patients.
      Sexual function is maintained in women undergoing open reconstructive aortic
      surgery. Patients with occlusive disease tend to have poorer preoperative sexual
      function than aneurysm patients. Compared to national norms, QOL is worse in
      women after aortic surgery.

PMID- 15156361
TI  - Elevated expression of matrix metalloproteinase-13 in abdominal aortic aneurysms.
AB  - Destructive remodeling of extracellular matrix has been shown to be present in
      aneurysmal abdominal aorta. We used real-time quantitative reverse transcriptase
      polymerase chain reaction to determine the relative expression of matrix
      metalloproteinase-13 (MMP13) in aortic tissue samples from patients who underwent
      abdominal aortic aneurysm repair operations (n = 36) and from nonaneurysmal
      autopsy samples (n = 20). The assays were carried out simultaneously in the same
      reaction tubes for ribosomal 18S RNA to correct for different amounts of input
      RNA. MMP13 was expressed in all parts of aorta and its expression was elevated in
      aneurysmal sac. In further studies using MMP13-specific antibody we demonstrated
      that MMP13 protein was present in the aneurysmal wall.

PMID- 15156363
TI  - Experience with cryopreserved cadaveric femoral vein allografts used for
      hemodialysis access.
AB  - The purpose of this study was to review the patency and complications of
      cryopreserved vein allografts used for hemodialysis access, and to compare them
      to a group with polytetrafluoroethylene (PTFE) grafts. Patients without adequate
      vasculature for native fistula were implanted with vein allografts or PTFE grafts
      at the surgeon's discretion. Only cryopreserved (CRY) veins were used until
      January 2001, when decellularized, cryopreserved Synergraft (SYN) veins became
      available. The CRY group had 48 patients; the SYN group, 42 patients; the PTFE
      group, 100 patients, who were selected from billing records listing PTFE graft
      insertion. Patient demographics were similar. Primary and secondary patencies
      were not significantly different at 1 or 2 years between groups. Complications in
      PTFE versus CRY and SYN groups were as follows: infection, 10 % vs. 0% (p <
      0.01); aneurysm, 2% vs. 18% (p < 0.001); and steal syndrome, 12% vs. 12% (p =
      NS). Significantly more vein allograft patients lost their accesses to aneurysm
      (p < 0.01) and multiple stenoses (p < 0.05), whereas PTFE patients lost
      significantly more accesses to infection (p < 0.01) and recurrent thrombosis (p <
      0.05). We conclude that cadaver vein allografts have similar patency to PTFE
      grafts. These allografts are more resistant to infection but significantly more
      susceptible to aneurysms. When used, vein allografts should be monitored
      aggressively for the development of aneurysms.

PMID- 15156364
TI  - Are varicose veins a marker for susceptibility to coronary heart disease in men?
      Results from the Normative Aging Study.
AB  - Clinical observations suggest that varicose veins (VV) are less frequent in
      patients undergoing infrainguinal bypass surgery for femoral artery occlusive
      disease. While some previous studies support this relationship, others report
      that VV are more prevalent in coronary heart disease patients (CHD). This study
      used the Normative Aging Study (NAS) population to examine the association
      between VV and symptomatic CHD. The incidence of CHD over 35 years of follow-up
      was determined in the 2280 initially healthy male volunteers enrolled in the NAS.
      The incidence of CHD in the VV population and the subjects without VV were
      compared using Kaplan-Meier survival curves and the log-rank test. A time
      dependent proportional hazards regression method was used to further explore the
      relationship between VV disease and subsequent development of CHD after adjusting
      for other cardiovascular risk factors. A total of 569 subjects (24.9%) were
      diagnosed with VV prior to the development of symptomatic CHD, and 1708 (75.1%)
      were not. Over 35 years of follow-up, 98 subjects with VV developed symptomatic
      CHD (17.2%), while 363 of those without VV subsequently developed symptomatic CHD
      (21.2%). Kaplan-Meier survival curves suggested a reduced risk of symptomatic CHD
      for subjects with VV (p = 0.0001). Further exploration of this relationship in a
      proportional hazards multivariate model showed VV to be associated with a 36%
      decreased risk of symptomatic CHD after adjusting for other recognized
      cardiovascular risk factors. In the NAS population, men with VV were less likely
      to develop symptomatic CHD over the 35+ years of follow-up than were subjects
      without VV.

PMID- 15156365
TI  - Acute abdominal aorta embolism caused by rupture of a cardiac hydatid cyst.
AB  - We report a case of an abdominal aortic embolism due to rupture of a cardiac
      hydatid cyst. This report emphasizes the diagnostic, preventative, and treatment
      options for hydatid cyst embolism of abdominal aorta. Echocardiography should be
      routinely performed in all patients with hydatid disease for possible involvement
      of the heart. This enables early diagnosis and treatment of cardiac echinococcus
      before life-threatening complications occur.

PMID- 15156366
TI  - In vitro activity and in vivo efficacy of antimicrobial-coated vascular grafts.
AB  - The serious medical consequences and costly management of infections associated
      with vascular grafts have prompted an expanding interest in examining the
      preventive efficacy of antimicrobial-coated vascular grafts. The purpose of
      antimicrobial coating of vascular grafts is to reduce bacterial colonization of
      the device and, hopefully, the occurrence of clinical infection. In this study we
      demonstrated that expanded-polytetrafluoroethylene vascular grafts coated with
      minocycline and rifampin provide broad-spectrum antimicrobial activity in vitro,
      as reflected by zones of inhibition, against Staphylococcus epidermidis, S.
      aureus, Enterococcus faecium, and Pseudomonas aeruginosa. We also showed in a
      rabbit model that subcutaneously placed minocycline/rifampin-coated vascular
      grafts have lower rates of staphylococcal device colonization (1/24 = 4% vs. 8/30
      = 27%, p = 0.033) and device-related infection (0/24 = 0% vs. 6/30 = 20%, p =
      0.028) than uncoated grafts. These promising results encourage the clinical
      evaluation of vascular grafts coated with minocycline and rifampin.

PMID- 15156367
TI  - The discovery of perforating veins.
AB  - Many authors of the 19th century are erroneously credited for their discovery of
      perforating veins. In this report, we show the first representations of
      perforating veins, dated 1793. These are from the German anatomist Justus
      Christian Von Loder, who correctly described most of the groups of perforating
      veins we currently know. These drawings have never appeared in the modern
      literature.

PMID- 15156368
TI  - Spontaneous recanalization of acute internal carotid artery occlusion.
AB  - Little is known about the natural course of internal carotid artery occlusion and
      its possible recanalization. We present here a case of spontaneous recanalization
      of an acutely occluded internal carotid artery, angiographically reported, which
      later allowed the patient to benefit from surgical treatment. These and other
      similar cases raise the possibility of a more frequent recanalization of this
      artery than previously considered. We suggest routine follow-up of these patients
      to detect this eventuality, which could influence clinical outcome and secondary
      prophylaxis strategies.

PMID- 15156369
TI  - Malignant epithelioid angiosarcoma of the external iliac vein presenting as
      venous thrombosis.
AB  - A case is reported of a 28-year-old female who initially presented with a right
      iliac deep venous thrombosis of unclear etiology. A stenosis in the iliac vein
      was seen, but no intrinsic or extrinsic mass was noted on multiple imaging
      studies. The patient presented 2 years later with right hydronephrosis, and at
      that time a right pelvic mass was discovered. Resection was performed with
      concomitant reconstruction of the right iliac arterial system, and pathology
      revealed a malignant epithelioid angiosarcoma.

PMID- 15156370
TI  - Characterization of molecular structures and properties of polyurethanes using
      molecular dynamics simulations.
AB  - Thermotropic polyurethanes with mesogenic groups in side chains were prepared
      from two diisocyanates and four diols with stoichiometric ratios of reactive
      isocyanate (NCO) and hydroxy (OH) groups. Their thermal behavior was determined
      by differential scanning calorimetry. The effect of structure modifications of
      the diisocyanates and diols, in particular changes in the mesogen, were
      investigated. Introduction of mesogenic segments into the polymers suppresses the
      ordering. Stiff end substituents (phenyl and alkoxy groups) of the mesogens
      stabilize the mesophases to such an extent that the negative influence of long
      polymer chains is compensated and the liquid-crystalline properties are
      recovered. All-atom molecular dynamics simulations in the Cerius2 modeling
      environment were carried out to characterize the structures of the polymers.
      Analysis of the dynamic trajectories at 20, 100, 120 and 170 degrees C revealed
      changes in conformation of macromolecules, which correlate with DSC measurements.

PMID- 15156371
TI  - Synthesis of novel types of copper-bipyridyl porphyrins and characterization of
      their interactions and reactivity with DNA.
AB  - The inherent ability to interact with DNA makes cationic metallo-porphyrins
      attractive targets as antitumor drugs. Many studies describe their interaction
      with DNA and the mechanism by which they induce DNA cleavage. Since porphyrins
      can be used as anchors for chemically reactive groups, it is possible to modify
      them to generate a family of compounds with specific functions. In the present
      work, we used chemical groups such as copper-bipyridinium (Cu-bpy), which
      hydrolyze phosphodiester bonds, and a porphyrin core to synthesize two novel
      Cu(2)-bpy-porphyrins. Their interactions with DNA have been characterized using
      classic spectroscopic methods, and their oxidative and hydrolytic reactivity
      toward supercoiled plasmid DNA has been studied in vitro. Our results show that
      Cu(2)-bpy-porphyrins interact with DNA via external association and intercalation
      and that their ability to cleave DNA and the mechanisms depends on the
      experimental conditions.

PMID- 15156372
TI  - A simple method for bone-graft handling during spine surgery.
AB  - Morsellized bone-graft handling during spine surgery to get vertebral fusion can
      be a slow, laborious and time-consuming procedure. It is not absolutely exempt
      from complication risk. An easy, quick and inexpensive alternative technique is
      described.

PMID- 15156373
TI  - Primary inguinal hernia repair: open or laparoscopic, that is the question.
      Point.

PMID- 15156376
TI  - Thrombosis in the portal venous system after elective laparoscopic splenectomy.
AB  - BACKGROUND: The occurrence of thrombosis in the portal system is an
      underappreciated complication of splenectomy. Presenting symptoms are usually
      mild and nonspecific. The short hospital stay associated with the laparoscopic
      approach could delay the early diagnosis of this condition unless routine imaging
      controls are planned after discharge. METHODS: The records of 40 patients who
      underwent laparoscopic splenectomy at our institution were reviewed for clinical
      signs of thrombosis in the portal system and associated factors. All patients
      were also enrolled in a color Doppler ultrasound surveillance program. RESULTS:
      Nine patients (22.5%) developed thrombosis of the splenic vein, progressing to
      the portal vein in five cases (12.5%). Six patients (15%) were symptomatic.
      Thrombosis occurred even as late as 4 months after splenectomy. Spleen weight was
      the only significant factor predictive of postoperative thrombosis. The
      combination of splenomegaly and an elevated preoperative platelet count was
      associated with a 75% incidence of this complication. CONCLUSION: The high risk
      of thrombosis after the laparoscopic resection of large spleens should prompt
      strict postoperative imaging surveillance, combined with a more aggressive
      anticoagulation prophylaxis.

PMID- 15156378
TI  - Appendix tumors in the era of laparoscopic appendectomy.
AB  - BACKGROUND: The safety of laparoscopic appendectomy for the management of
      incidentally discovered appendiceal tumors has not yet been established. METHODS:
      Appendiceal tumor cases managed by laparoscopy or laparotomy over a 10-year
      period were reviewed. RESULTS: The pathological diagnoses were 23 carcinoid and
      20 cancerous lesions. The median patient ages were 36 and 69 years, respectively,
      for carcinoid and other tumors (p < 0.05). Acute appendicitis was present in 70%
      of carcinoid cases and 35% of other tumors (p < 0.05). Eight patients with
      carcinoid tumors were operated on by laparoscopy, whereas 15 underwent
      laparotomy. Laparoscopic and open procedures were performed in three and 17
      patients with cancerous lesions, respectively. Invaded surgical margins were seen
      after laparoscopy in 20% of patients and open surgery in 6%. Synchronous colon
      carcinoma was detected in 14% of the patients with an appendix neoplasm. The 5
      year survival rates were similar after both laparoscopic and open appendectomy
      for either carcinoid or other tumors. CONCLUSION: Laparoscopic appendectomy for
      appendiceal tumors seems to have a slightly higher rate of inadequate resection.
      However, it is not associated with a significantly worse patient prognosis than
      open appendectomy.

PMID- 15156379
TI  - Improving laparoscopy in embalmed cadavers: a new method with a lateral abdominal
      wall muscle section.
AB  - BACKGROUND: Rigor mortis can be a problem when laparoscopy is performed in
      embalmed cadavers for surgical training. METHODS: To improve the laparoscopic
      view, a new technique for managing the abdominal wall with a cutaneous
      subcutaneous flap, pneumoperitoneum (14-15 mmHg), and a progressive (step-by
      step) bilateral section of the lateral muscles of the abdomen was attempted in 10
      embalmed cadavers. The degree of abdominal wall increase was calculated by
      measuring changes in the size of the abdominal wall after each step. Improvement
      in the peritoneal laparoscopic view was also assessed. RESULTS: For abdominal
      wall size, no constant relationship was observed between initial (after creation
      of the pneumoperitoneum) and final increment (after each muscular layer section).
      Cumulative degrees of increase in the dimensions of the abdominal wall were the
      only parameters that showed a significant difference among the four groups of
      cadavers. Bilateral sectioning of both oblique muscles was sufficient to obtain
      an adequate view of the abdominopelvic cavity; thus, the risk of an unexpected
      peritoneal opening during sectioning of the transversum abdominis muscle was
      obviated. CONCLUSIONS: In embalmed cadavers, the laparoscopic view in the
      presence of a pneumoperitoneum can be facilitated by a section of the lateral
      muscles of the abdomen, with a previous cutaneous-subcutaneous flap. To obviate
      an incidental opening of the peritoneum, resulting in air leakage, preservation
      of the deep muscular layer is advisable.

PMID- 15156380
TI  - Mid term analysis of safety and quality of life after the laparoscopic repair of
      paraesophageal hiatal hernia.
AB  - BACKGROUND: Initial experience with the laparoscopic repair of paraesophageal and
      type III mixed hiatal hernias showed that it is safe and feasible, with excellent
      immediate and short-term results. However, after a longer follow-up, a recurrence
      rate of < or =40% has been demonstrated. Data related to the outcome of
      paraesophageal hernia repair and the recurrence rate are still lacking. Quality
      of-life scores may offer a better means of assessing the impact of surgical
      treatment on the overall health status of patients. Therefore, we performed
      prospective evaluation of anatomic and/or symptomatic recurrences after
      paraesophageal or large hiatal hernia repair. In addition, we investigated the
      correlation between recurrence and the patient's quality of life. METHODS: All
      patients after who had undergone repair of paraesophageal of mixed hiatal hernia
      were identified prospectively from a database consisting of all patients who had
      had laparoscopic operations for gastroesophageal pathology at our hospital
      between February 1998 and December 2002. The preoperative symptoms were taken
      from patients' clinical files. In March 2003, all patients with > or =6 months of
      follow-up had a barium swallow and were examined for radiological and clinical
      signs of recurrence. Thereafter, the patients' quality of life after surgery was
      evaluated using three standard questionnaires (Short Form 36 [SF-36], Glasgow
      Dyspepsia Severity Score [GDSS], and Gastrointestinal Quality of Life Index
      [GIQLI]. RESULT: During the study period, 46 patients had been operated on. The
      mean age was 63 years (range, 28-93). Thirty seven of them had a follow-up of >
      or =6 months. Eight patients (21%) had postoperative gastrointestinal symptoms.
      Barium swallow was performed in 30 patients (81%) and showed a recurrence in six
      of them (20%). According to SF-36 and GDSS, the patients' postoperative quality
      of life reached normal values and did not differ significantly from the standard
      values for the Spanish population of similar age and with similar comorbidities.
      Successfully operated patients reached a GIQLI value comparable to the standard
      population. However, symptomatic patients had significantly lower GIQLI scores
      than the asymptomatic or the Rx-recurrent group. CONCLUSION: The laparoscopic
      treatment of large paraesophageal and mixed hiatal hernias is not only feasible
      and safe but also offers a good quality of life on a midterm basis. However, the
      anatomic and functional recurrence rate is high. The next step is to identify the
      subset of patients who are at risk of failure and to establish technical
      alternatives that would ensure the durability of the repair.

PMID- 15156381
TI  - Laparoscopic-assisted colectomy in patients with liver cirrhosis.
AB  - BACKGROUND: Nonhepatic abdominal surgery, and especially colorectal surgery, is
      associated with high rates of morbidity and mortality among cirrhotic patients.
      With proper patient selection and preoperative optimization of the patient's
      condition, laparoscopic-assisted colectomy could become effective and safe for
      patients with compensated liver cirrhosis. The aim of this study was to evaluate
      the safety and feasibility of minimal-access surgery in these patients. METHODS:
      Between September 1993 and March 2003, 820 patients underwent laparoscopic
      assisted colectomy at our hospital. We studied all patients with liver cirrhosis
      who underwent this operation. RESULTS: Seventeen patients with cirrhosis were
      included in the study. Twelve were Child's A and five were Child's B. The mean
      operative time was 150 min (ranges 75-280), mean estimated blood loss was 245 ml
      (ranges 100-250). The conversion rate to open surgery was 29% (five patients).
      Median length of hospital stay was 5 days. The morbidity rate was 29% (five
      patients). There were no anastomotic leaks or operative-related deaths. The
      median follow-up was 21 months. CONCLUSIONS: Laparoscopic-assisted colorectal
      surgery can be performed in compensated cirrhotic patients with low morbidity and
      mortality. Adequate patient selection and expertise in advanced minimal-access
      surgery are essential to obtain such good results.

PMID- 15156382
TI  - Laparoscopic lateral pancreaticojejunostomy: our experience of 17 cases.
AB  - BACKGROUND: Although lateral pancreaticojejunostomy (LPJ) is one of the most
      commonly performed procedures for the management of chronic obstructive
      pancreatitis, it is seldom performed laparoscopically. We report our experience
      of 17 consecutive laparoscopic LPJ (lap LPJ) and their outcome. METHODS:
      Seventeen patients (nine male and eight female) with ages ranging between 16 and
      48 years underwent lap LPJ by a single surgical team. The most common presenting
      symptoms were abdominal pain and weight loss. RESULTS: The mean operating times
      for lap LPJ and lap LPJ with one or more additional procedures were 277 min and
      377 min, respectively. The mean hospital stay was 5.2 days. Conversion to
      laparotomy was required in four patients. There were no deaths and the overall
      complication rate was 11.8%. On follow-up, ranging from 3 months to 1 year, 82.3%
      of the patients were pain-free. CONCLUSIONS: Lateral pancreaticojejunostomy is
      the surgical procedure of choice for the management of chronic obstructive
      pancreatitis. The same procedure can be performed laparoscopically; although it
      is technically demanding, the results are excellent. However, the procedure is
      still in the early phase of feasibility owing to the limited number of cases
      reported in the world literature.

PMID- 15156383
TI  - Prevention of recurrence by reinforcement of hiatal closure using ligamentum
      teres in laparoscopic repair of large hiatal hernias.
AB  - BACKGROUND. Several attempts were made to develop an effective technique to
      reduce the high recurrence rate associated with the repair of large hiatal
      hernias. METHODS: A new laparoscopic technique was introduced to reinforce hiatal
      closure with the ligamentum teres. Its feasibility, safety, and efficacy were
      evaluated. Four patients with gastroesophageal reflux disease and large hiatal
      hernia (>6 cm) entered the study. After closure of the diaphragmatic crura the
      teres ligament was dissected, brought behind the esophagus, and sutured to the
      crura. A fundoplication was also added. Patients were followed with barium
      swallow at 3 months postoperatively. RESULTS: The mean operation time was 109.5
      min. No intraoperative complications, perioperative morbidity, or mortality were
      registered. At the follow-up, barium swallows revealed no recurrence. CONCLUSION:
      On the basis of these preliminary results laparoscopic reinforcement of the
      hiatal closure with the ligamentum teres seems feasible and safe; therefore this
      promising technique should be considered as an option for the treatment of large
      hiatal hernias.

PMID- 15156384
TI  - Laparoscopy as a prognostic factor in curative resection for node positive
      colorectal cancer: results for a single-institution nonrandomized prospective
      trial.
AB  - BACKGROUND: Several studies reporting preliminary long-term survival data after
      laparoscopic resections for colonic adenocarcinoma did not show any detrimental
      effect in comparison with historic studies of laparotomies. A previous randomized
      study has reported an unforeseen better long-term survival for node-positive
      patients treated by laparoscopic colectomy. METHODS: A single-institution
      prospective nonrandomized trial compared short- and long-term results of
      laparoscopic and open curative resection for adenocarcinoma of the left colon or
      rectum in 255 consecutive patients from January 1996 to December 2000. RESULTS:
      In this study, 34 left hemicolectomy, 202 anterior resections, and 19
      abdominoperineal resections were performed. A total of 74 patients underwent a
      laparoscopic resection (LR), and 181, an open resection (OR). The tumor site was
      the descending colon in 32 cases, the sigmoid colon in 98 cases, and the rectum
      in 125 cases, including 87 mid-low rectal cancers. Ten LR procedures (13.5%) were
      converted to open surgery. The hospital mortality was 0.08%, and in hospital
      morbidity was 16.2% for LR and 13.3% for OR (p = 0.56). The median postoperative
      stay was 1 day shorter for LR (9 days) than for OR (10 days) (p = 0.09). The mean
      number of lymph nodes retrieved were 13.8 +/- 5.7 for OR and 12.7 +/- 5; for LR
      (p = 0.23). Age exceeding 70 years, T stage, N stage, grading, mid-low rectal
      site, and laparoscopy were found by multivariate analysis to be significant
      prognostic factors for disease-free and cancer-related survival. When patients
      were stratified by stage, a trend toward a better disease-free and cancer-related
      survival was identified in stage III patients undergoing LR. CONCLUSIONS:
      Laparoscopic colonic resection is a safe procedure in terms of postoperative
      outcome and long-term survival. Multivariate analysis showed that laparoscopy is
      a positive prognostic factor for disease-free and cancer-related survival. The
      current data agrees with the data for the only randomized study reported so far.
      Both suggest a better outcome for node-positive patients treated by laparoscopy.

PMID- 15156385
TI  - Minilaparoscopy in the diagnosis of peritoneal tumor spread: prospective
      controlled comparison with computed tomography.
AB  - BACKGROUND: Early diagnosis of peritoneal spread in malignant disease prevents
      unnecessary laparotomies. Minimally invasive laparoscopy with the patient under
      conscious sedation is a new, easily feasible diagnostic technique. This study
      compares prospective and controlled diagnostic minilaparoscopy with computed
      tomography (CT) scan for the diagnosis of peritoneal metastases. METHODS: In this
      study, 56 patients with malignant disease were prospectively investigated with
      diagnostic minilaparoscopy and CT scan. RESULTS: The study criteria were
      fulfilled by 54 patients. Minilaparoscopy detected peritoneal carcinosis in 28 of
      54 cases, whereas CT detected the disease in 14 of 54 cases. For 36 patients, the
      diagnosis could be verified by histologic examination of peritoneal biopsies or
      laparotomy. In this group, minilaparoscopy detected peritoneal carcinosis in 25
      of 36 cases, whereas CT detected the disease in 12 of 36 cases. CONCLUSIONS:
      Minilaparoscopy was more sensitive than CT in detecting peritoneal carcinosis
      (100% vs 47.8%; p < 0.01). Considering its low grade of invasiveness and superior
      sensitivity, minilaparoscopy should be regarded as the procedure of choice for
      the early detection of peritoneal carcinosis.

PMID- 15156386
TI  - Outcome after intra- and extra-corporeal laparoscopic appendectomy techniques.
AB  - BACKGROUND: This study aimed to assess the outcome after intracorporeal (IC) and
      extracorporeal (EC) laparoscopic appendectomy technique in a single institution
      over a 5-year period. METHODS: Records of all children ( n = 60) who underwent
      laparoscopic appendectomy at the Royal Aberdeen Children's Hospital between
      February 1997 and March 2002 were retrieved and evaluated. Observations were made
      regarding operative technique, anesthetic time, intra- and postoperative
      complications, postoperative analgesic requirement, and postoperative hospital
      stay. RESULTS: There were 30 children in each group who had a similar demographic
      profile. The magnitude of appendicitis severity in both groups was similar. The
      mean anesthetic time was 67.8 min for the IC group and 50.7 min for the EC group
      (p = 0.001). There were no recorded intraoperative complications, although a
      single case in the EC group required conversion to open procedure. The
      postoperative analgesic requirement in both groups was similar. The mean
      postoperative stay was 2.1 days in the IC group and 2.5 days in the EC group. Two
      postoperative complications were noted in the IC group; one intraperitoneal
      collection and one postoperative chest infection. Four complications occurred in
      the EC group; one intraperitoneal collection and three minor port-site wound
      infections. CONCLUSIONS: The authors' experience shows the EC technique to be
      significantly quicker, although with a slightly increased complication rate.
      Either technique can be applied safely for acute appendicitis.

PMID- 15156387
TI  - Laparoscopic identification of pelvic nerves in patients with deep infiltrating
      endometriosis.
AB  - BACKGROUND: Nerve sparing is suggested for cancer surgery, but no experience is
      available for deep endometriosis. The aim of this study was to laparoscopically
      identify the pelvic nerves in the posterior pelvis. METHODS: A total of 24
      patients operated for deep endometriosis were considered. During surgery and on
      videotapes of the procedures, we evaluated single- or double-sided resection of
      the uterosacral ligaments and other structure's visualization of the inferior
      hypogastric and the splanchnic nerves. The most important objective criteria for
      resection of the nerves was urinary retention after surgery, which was compared
      to surgical resection on the videotapes. RESULTS: Visualization of the inferior
      hypogastric nerves was possible in 20 of 22 patients (90.1%). Eight of the 24
      patients had at least one inferior hypogastric nerve resected (33.3%). In seven
      patients (29.2%) resection of the uterosacral ligaments was bilateral, and in
      three of these the nerves were resected. Postoperatively, the median residual
      urine volume after the first spontaneous voiding was 40 ml (range, 20-400). Seven
      of eight patients (29.2%) with resection of the nerves had urinary retention and
      self-catheterization at discharge. The difference in urinary residuum after first
      voiding between patients undergoing self-catheterization and patients released
      without the catheter was significant ( p < 0.01). The median time to resume the
      voiding function in patients with self-catheterization was 18 days (range, 9-45).
      CONCLUSIONS: Nerve visualization is possible by means of laparoscopic surgery for
      deep endometriosis in a high rate of patients. Careful technique is necessary,
      but the laparoscopic approach may help. Even single-sided radical dissection can
      induce important urinary retention.

PMID- 15156388
TI  - The value of endosonographic rectal carcinoma staging in routine diagnostics: a
      10-year analysis.
AB  - BACKGROUND: Endosonography is currently the gold standard for the local staging
      of rectal carcinoma, but its accuracy varies from 62% to 91%. This study aimed to
      determine the accuracy of endosonography, to evaluate the interobserver
      variability, and to compare the performance of the 7.5-MHz and the 10-MHz
      ultrasound scanners. METHODS: Between 1990 and 2000, 458 patients with rectal
      cancer were included in the study. All the patients had undergone rectal
      endosonography with a 7.5-MHz scan (period 1: 1990-1996) or a 10-MHz scan (period
      2: 1997-2000). Endosonographic staging was compared with pathologic staging.
      RESULTS: The overall rate for correctly classified patients was 69% with respect
      to the T category and 68% with respect to the N category. There was no difference
      between the two scanners. In terms of accuracy, the T3 category tumors were the
      most (86%) and the T4 tumors the least (36%) accurately classified. Overstaging
      of tumors (19%) was much more frequent than understaging (12%). A high
      interobserver variability of 61% to 77% was noted. For pT1 tumors, the 10-MHz
      scan was almost two times more accurate than the 7.5-MHz scan (71% vs 36%).
      CONCLUSIONS: The accuracy of endosonographic staging of rectal carcinoma very
      much depends on the T category. A high-resolution scanner and an experienced
      examiner can help to ensure that endosonography remains an important tool in the
      staging process of patients with rectal carcinoma, especially early carcinoma.

PMID- 15156389
TI  - A nickel-titanium memory-shape device for colonic anastomosis in laparoscopic
      surgery.
AB  - BACKGROUND: Minimally invasive surgery is used increasingly for colonic
      resection. With this procedure, the involved colon is dissected laparoscopically
      and exteriorized through a small incision, and the segment containing the tumor
      is resected. The anastomosis is performed extraperitoneally either by hand suture
      or with a stapler. This study was designed to evaluate the feasibility of using a
      memory-shape compression anastomosis clip (CAC) to perform laparoscopically
      assisted colonic anastomosis. The study was prompted by the authors' successful
      experience with the CAC in an animal model and in 10 patients with diverse
      colonic cancers. METHODS: The sample consisted of 10 patients who underwent
      laparoscopic colonic surgery at the authors' center. The anastomosis was
      performed with the CAC for five patients and with a stapler for five patients. To
      perform anastomosis with the CAC, the two edges of the resected colon are
      aligned. Two 5-mm incisions are made near the edges, through which the CAC, after
      cooling in ice water, is introduced in an open position using a special applier.
      In response to body temperature, the clip resumes its original (closed) position,
      thereby clamping the two bowel loops together. At the same time, the small
      scalpel incorporated in the applier makes a small incision through the clamped
      walls for the passage of gas and feces, and the clip is released into the
      intestine. The two 5-mm incisions are sutured. The clip is expelled with the
      stool within 5 to 7 days, creating a perfect uniform anastomosis. RESULTS:
      Neither group had complications, except one patient from the control group who
      experienced a small bowel obstruction attributable to a wound suture problem,
      which required laparotomy. His recovery was uneventful. CONCLUSIONS: The use of
      the CAC for colonic laparoscopic surgery is simple and very efficient, shortening
      operation time. It creates a uniform anastomosis, approximating the no-touch
      concept in surgery, and may prevent infection. It also is lower in cost than the
      stapler.

PMID- 15156390
TI  - Results after endoscopic treatment of postoperative upper gastrointestinal
      fistulas and leaks using combined Vicryl plug and fibrin glue.
AB  - BACKGROUND: The incidence of clinically relevant anastomotic leaks after upper
      gastrointestinal surgery is approximately 4% to 20%, and the associated mortality
      is up to 80%. Depending on the clinical presentation, the treatment options
      include surgery, conservative treatment with or without external drainage or
      endoscopic treatment. METHODS: This report presents nine cases of anastomotic
      leaks or fistulae after surgery for upper gastrointestinal cancers that were
      treated by insertion of a Vicryl plug and sealing with fibrin glue. Under
      sedation, all nine patients underwent endoscopic lavage of the cavity at the site
      of anastomotic leakage. The entrance to the cavity then was filled with Vicryl
      mesh and sealed off with fibrin glue. After the procedure, the patients underwent
      endoscopy and a water-soluble contrast study for assessment of the result.
      RESULTS: Seven of the nine patients had complete healing of the anastomotic leak
      or fistula after one to two endoscopic treatments. In one case, the treatment
      failed immediately because of a large and direct tracheoesophageal fistula.
      Another patient experienced recurrent intrathoracic abscesses after initial
      technical success. CONCLUSIONS: Postoperative upper gastrointestinal fistulas or
      anastomotic leaks can be managed successfully with little morbidity by means of
      endoscopic insertion of Vicryl mesh with fibrin glue, thereby avoiding repetitive
      major surgery and its associated risks.

PMID- 15156391
TI  - Robot-assisted minimally invasive Kasai portoenterostomy: a survival porcine
      study.
AB  - BACKGROUND: Major enhancements offered by robotic surgery for minimally invasive
      procedure include tremor filtration, motion scaling, and the addition of a wrist
      to the instrument. Minor enhancements include indexing as well as safe and rapid
      instrument exchange. A benefit associated with any endoscopic procedure is
      magnification. It was hypothesized that these enhancements would allow the
      performance of complex gastrointestinal surgery. METHODS: Eight survival pigs
      (weight, 2.5-8 kg) underwent a robotically assisted minimally invasive
      portoenterostomy. The procedure was analogous to the Kasai portoenterostomy for
      biliary atresia usually performed for human patients at the age of 4 to 12 weeks.
      RESULTS: Five of the eight animals survived for more than 1 month after the
      operation, returning to normal eating and bowel habits in 2 to 3 days. None were
      jaundiced. All laboratory values were normal. At 1 month, the animals were
      killed. There was no anastomotic stenosis at either the end-to-side
      enteroenterostomy or the portoenterostomy. Histologically, the anastomoses were
      well healed. CONCLUSION: Computer-assisted robot-enhanced technology allows
      complex gastrointestinal surgery to be performed using minimally invasive
      techniques.

PMID- 15156392
TI  - Changes in GERD symptom scores correlate with improvement in esophageal acid
      exposure after the Stretta procedure.
AB  - BACKGROUND: Endoscopic radiofrequency energy delivery (Stretta) is effective for
      managing gastroesophageal reflux disease (GERD) in selected patients. One
      criticism, however, is a theory that a mechanism of action is partial
      desensitization of the esophageal body rather than a reduction in esophageal acid
      exposure. To resolve this question, this study sought to determine if there is a
      correlation between the improvement in GERD outcomes and esophageal acid exposure
      after Stretta. METHODS: Subgroup analyses were performed between "responder" and
      "nonresponder" groups from the U.S. Stretta open label trial ( n = 118), on the
      basis of posttreatment responses for GERD health-related quality of life (HRQL)
      heartburn, satisfaction, and proton pump inhibitor use. Outcomes were analyzed
      within and between subgroups. Pearson correlation coefficient analysis was
      performed comparing distal esophageal acid exposure with each of the continuous
      outcomes (GERD-HRQL, heartburn, satisfaction). RESULTS: Responder subgroups had
      significant improvements in esophageal acid exposure, whereas nonresponders had
      no change or less improvement in the same. Changes in GERD-HRQL and heartburn
      severity were correlated with changes in acid exposure ( r = 0.16, p = 0.12 and r
      = 0.26, p = 0.01, respectively). Changes in satisfaction were negatively
      correlated with changes in esophageal acid exposure ( r = 0.23, p = 0.02) because
      satisfaction, as expected, increased as acid exposure decreased. CONCLUSIONS:
      Responders had significant improvement in esophageal acid exposure, whereas
      nonresponders had less or no change. There was a positive correlation between
      esophageal acid exposure and both GERD-HRQL and heartburn. This evidence suggests
      that symptomatic improvement after Stretta is attributable to a decrease in
      esophageal acid exposure and not to desensitization of the esophagus.

PMID- 15156393
TI  - Preperitoneal bupivacaine attenuates pain following laparoscopic inguinal hernia
      repair.
AB  - BACKGROUND: Laparoscopic preperitoneal inguinal hernia repair is associated with
      a short hospital stay and an early return to normal activity. Therefore, early
      postoperative pain control is important. The aim of this study was to evaluate
      the effect of preperitoneal Bupivacaine instilled into the preperitoneal cavity
      on pain following laparoscopic mesh repair of inguinal hernia. METHODS: After
      institutional review board approval, 44 patients undergoing elective laparoscopic
      inguinal hernia repair were prospectively randomized into two groups. Upon
      completion of the Prolene mesh repair, group A received 80 mg of Bupivacaine in
      25 cc of saline installed into the preperitoneal space, whereas group B received
      normal saline installed into the preperitoneal space. Pain was assessed using a
      visual analog scale at fixed time intervals; the amount of analgesics required
      was also recorded. RESULTS: Twenty-two patients were included in each group. The
      demographic characteristics and type of surgery (unilateral vs bilateral) did not
      significantly differ between the two groups. The average pain levels were
      significantly attenuated in group A compared to group B at 1 (4.0 vs 5.0,
      respectively; p = 0.0038), 2 (4.0 vs 5.9, respectively; p = 0.0015), and 4 (4.3
      vs 5.8, respectively; p = 0.0038) h after surgery. Furthermore, the analgesic
      intake was significantly decreased in group A compared to group B. CONCLUSION:
      Preperitoneal Bupivacaine attenuates pain following laparoscopic inguinal hernia
      repair and should be considered in these cases.

PMID- 15156394
TI  - Incidence of clinically evident deep venous thrombosis after laparoscopic Roux-en
      Y gastric bypass.
AB  - BACKGROUND: Advanced age, major orthopedic surgery, neoplastic disease, prolonged
      operations, varicose veins, immobilization, estrogen-containing medications, and
      obesity are known risk factors for the development of postoperative
      thromboembolic complications. Perioperative heparin is useful for reducing the
      incidence of deep venous thrombosis (DVT), but it is associated with a discrete
      bleeding rate. The purpose of this study was to determine the incidence of
      clinically evident DVT in morbidly obese patients after laparoscopic Roux-en-Y
      gastric bypass when a pneumatic compression hose is used as the only prophylaxis
      against DVT instead of anticoagulants. METHODS: From April 2000 to April 2003,
      380 patients underwent laparoscopic Roux-en-Y gastric bypass for morbid obesity
      by one surgeon (R.H.C.). Prospectively, each patient was clinically evaluated for
      the presence of DVT during the postoperative period. Calf-length pneumatic
      compression stockings were placed before the procedure began, and remained in
      place until the patient was ambulatory. Ambulation was encouraged on the evening
      of the operation. No pharmacologic anticoagulant was used as a prophylaxis
      against DVT. RESULTS: Of the 380 patients, 346 were women and 34 were men with a
      mean age of 39.3 +/- 9.4 years (range, 14-65 years). The mean weight of these
      patients was 299.5 +/- 53.6 lb (range, 188-483 lb), and their mean body mass
      index was 48.5 +/- 6.6 (range, 36-70). The mean operative time was 103. 3 +/-
      24.3 min (range, 62-227 min), and mean American Society of Anesthesiology (ASA)
      score was 2.6. Nine patients had clinical evidence of severe, chronic venous
      disease preoperatively. One patient (0.26%) experienced a clinically evident DVT
      limited to the popliteal vein on duplex ultrasonography. The clot resolved
      completely, as evidenced by follow-up duplex ultrasonography after 2 weeks of
      subcutaneously injected fractionated heparin. No clinically evident pulmonary
      thromboembolism occurred in this study group. CONCLUSIONS: The incidence of
      clinically evident DVT after laparoscopic Roux-en-Y gastric bypass is low when
      the procedure is accomplished with a relatively short operative time, with the
      initiation of calf-length pneumatic compression hose before the induction of
      anesthesia, and with routine early ambulation. No form of heparin anticoagulation
      is mandatory when these conditions can be met.

PMID- 15156396
TI  - Equine Cryptosporidium parvum infections in western Poland.
AB  - A total of 564 fecal specimens from 318 horses used for recreational riding,
      child hippotherapy, and racing at ten commercial and government-run stables in
      western Poland were tested for Cryptosporidium parvum oocysts by microscopic
      examination of Ziehl-Neelsen stained smears, enzyme immunoassay, and combined
      direct immunofluorescent antibody and fluorescent in situ hybridization. Also,
      seven stool specimens from five personnel who had repeated contact with these
      horses were tested for C. parvum oocysts. Eleven horses that shed C. parvum
      oocysts were found in five of ten stables (50%). The prevalence of infection
      varied from 0% to 11.5%. The overall prevalence of equine C. parvum-associated
      cryptosporidiosis in the Wielkopolska region of western Poland was 3.5%. C.
      parvum oocysts were found only in fecal samples from mature horses, the number of
      oocysts was low, and infections were not associated with clinical signs. Oocysts
      were not found in human fecal specimens.

PMID- 15156395
TI  - Water relations in grassland and desert ecosystems exposed to elevated
      atmospheric CO2.
AB  - Atmospheric CO2 enrichment may stimulate plant growth directly through (1)
      enhanced photosynthesis or indirectly, through (2) reduced plant water
      consumption and hence slower soil moisture depletion, or the combination of both.
      Herein we describe gas exchange, plant biomass and species responses of five
      native or semi-native temperate and Mediterranean grasslands and three semi-arid
      systems to CO2 enrichment, with an emphasis on water relations. Increasing CO2
      led to decreased leaf conductance for water vapor, improved plant water status,
      altered seasonal evapotranspiration dynamics, and in most cases, periodic
      increases in soil water content. The extent, timing and duration of these
      responses varied among ecosystems, species and years. Across the grasslands of
      the Kansas tallgrass prairie, Colorado shortgrass steppe and Swiss calcareous
      grassland, increases in aboveground biomass from CO2 enrichment were relatively
      greater in dry years. In contrast, CO2-induced aboveground biomass increases in
      the Texas C3/C4 grassland and the New Zealand pasture seemed little or only
      marginally influenced by yearly variation in soil water, while plant growth in
      the Mojave Desert was stimulated by CO2 in a relatively wet year. Mediterranean
      grasslands sometimes failed to respond to CO2-related increased late-season
      water, whereas semiarid Negev grassland assemblages profited. Vegetative and
      reproductive responses to CO2 were highly varied among species and ecosystems,
      and did not generally follow any predictable pattern in regard to functional
      groups. Results suggest that the indirect effects of CO2 on plant and soil water
      relations may contribute substantially to experimentally induced CO2-effects, and
      also reflect local humidity conditions. For landscape scale predictions, this
      analysis calls for a clear distinction between biomass responses due to direct
      CO2 effects on photosynthesis and those indirect CO2 effects via soil moisture as
      documented here.

PMID- 15156397
TI  - Molecular systematics of several cyclophyllid families (Cestoda) based on the
      analysis of 18S ribosomal DNA gene sequences.
AB  - The sequences of the 18S small subunit ribosomal DNA of five species of
      cyclophyllidean cestodes from the families Davaineidae, Anoplocephalidae and
      Dilepididae were determined. A species of tetrabothridid was also sequenced.
      These 18S sequences were combined with other available eucestode sequences in
      GenBank. From the 1,838 sites in the alignment, 375 bp (20%) were excluded from
      the analysis due to alignment issues inferred by manual inspection. Phylogenetic
      trees were obtained by maximum parsimony, neighbour-joining distance and maximum
      likelihood methods. Analyses showed that Cyclophyllidea is monophyletic and
      separate from Tetrabothrius spp. Lyruterina nigropunctata, which is now included
      in the family Paruterinidae, is more closely related to davaineids of the genus
      Raillietina than Pseudidiogenes nana (Davaineidae). P. nana and Choanotaenia
      infundibulum (Dilepididae) derive from the Davaineidae (or Raillietininae). The
      two species of Taenia (T. parva and T. pisiformis) formed a monophyletic sister
      group to the Davaineidae and Anoplocephalidae. The systematics of the
      Paruterinidae have been problematic and our results suggest a review of this
      family including other species with paruterine organ located in other families.
      The position of the Idiogeninae as a subfamily in the Davaineidae is also
      reviewed.

PMID- 15156399
TI  - Seroprevalence of HSV-1 and HSV-2 in Barbados.
AB  - Type-specific enzyme-linked immunosorbent assays, based upon recombinant
      glycoprotein G (gG), were used to detect antibodies to HSV-1 and HSV-2, in a
      small Caribbean island population. A blinded serosurvey was performed on samples
      from 184 blood donors, 122 pregnant women, and 120 HIV-positive patients. The
      seroprevalence of HSV-1 and HSV-2 was 81% and 34%, respectively, in blood donors,
      84% and 40% in the antenatal population and 89% and 77% in the HIV-positive
      group. As expected the majority of adults were seropositive against HSV-1.
      However, the HSV-2 seroprevalence was significantly higher in HIV-infected adults
      than in the other groups. These findings support the need for prospective
      epidemiological studies in this population.

PMID- 15156398
TI  - Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and
      overexpression of antiapoptotic proteins in ovarian cancer.
AB  - GOALS: Resistance to cisplatin is the main reason for treatment failure in
      ovarian cancer. Apoptosis is the main mechanism of action of most cancer
      chemotherapeutic agents. The apoptosis-associated proteins expressed in cisplatin
      sensitive (A2780, COC1) and -resistant (A2780/DDP, COC1/DDP) ovarian cancer cell
      lines, as well as their effects on caspase-3 activity in these cells, were
      studied by reverse transcriptase polymerase chain reaction and Western blot
      analysis. METHODS: The apoptotic ratios of A2780, COC1, A2780/DDP, and COC1/DDP
      cells after treatment with cisplatin were measured by flow cytometry. RESULTS:
      Expression of Bcl-2 and Bcl-X(L) in A2780/DDP and COC1/DDP cells was
      significantly higher than that in A2780 and COC1 cells, respectively. Expression
      of Bax and Bcl-Xs did not differ in cisplatin-resistant and -sensitive cells.
      Caspase-3 activity was reduced markedly and apoptotic ratios were significantly
      lower in A2780/DDP and COC1/DDP cells than in A2780 and COC1 cells after
      treatment with cisplatin. CONCLUSION: We conclude that overexpression of
      antiapoptotic proteins Bcl-2 and Bcl-X(L) and down-regulation of caspase-3
      activity may be associated with cisplatin resistance in human ovarian cancer.

PMID- 15156400
TI  - Immunohistochemical demonstration of salmon olfactory glutathione S-transferase
      class pi (N24) in the olfactory system of lacustrine sockeye salmon during
      ontogenesis and cell proliferation.
AB  - In mammals, glutathione S-transferase (GST) in the olfactory epithelium is
      involved in assistance of the olfactory reception by the xenobiotic metabolism.
      We previously reported the protein and gene expressions of salmon olfactory GST
      class pi (soGST) in the olfactory receptor cells (ORCs) of the salmonid fish.
      However, the chronological appearances of soGST in ORCs during ontogeny and cell
      proliferation are still unknown in this species. In this study, we performed
      immunohistochemistry of soGST using an antibody specific to soGST in the
      olfactory system (olfactory placode, olfactory pit, olfactory epithelium,
      olfactory nerve and olfactory bulb) of lacustrine sockeye salmon ( Oncorhynchus
      nerka) embryos and 5-bromo-2'-deoxyuridine (BrdU) experimental fish. The
      projection of olfactory nerve bundles from the olfactory pit to the presumptive
      olfactory bulb was identified at embryonic day 28 after fertilization. The
      olfactory cilia were first detected on the apical surface of ORCs at day 43.
      soGST-immunoreactivity was first detected within the olfactory pit cells at day
      55. At 58 day, the number of soGST-immunoreactive cells increased markedly in the
      olfactory epithelia, and soGST-immunoreactive fibers were observed in the
      olfactory nerves and olfactory bulbs. By in vivo uptake of BrdU in 1-year-old
      fish, we observed for the first time at day 7 after labeling that the olfactory
      epithelia showed ORCs in which both soGST-immunoreactivity and BrdU coexisted.
      These results indicate that soGST is synthesized in the mature ORCs of lacustrine
      sockeye salmon after cell formation and differentiation.

PMID- 15156401
TI  - Runx2-deficient mice lack mandibular condylar cartilage and have deformed
      Meckel's cartilage.
AB  - Runx2 (runt-related transcription factor 2) deficient mice lacked the mandibular
      condylar cartilage and the mandibular bone. The anlage of the condylar process
      consisted of mesenchymal condensation, which expressed Type I collagen mRNA and
      alkaline phosphatase activity, but not Type II collagen and aggrecan mRNAs.
      Therefore, the differentiation of the mandibular condylar cartilage stopped at
      the preosteoblast (skeletoblast) stage. The lateral pterygoid muscle was attached
      to this anlage, and relatively abundant mesenchymal condensations were also
      formed at the muscle-attaching sites, e.g. the anlage of the mandibular body, the
      angular and coronoid processes. Three-dimensional reconstruction models showed
      that each mesenchymal condensation was connected to one another, and roughly
      outlined the shape of the mandible. Meckel's cartilage in the Runx2-deficient
      mice had two ectopic cartilaginous processes to which the digastric and myohyoid
      muscles were attached. These findings indicate that Runx2 is essential for the
      formation of the mandibular condylar cartilage, as well as for normal development
      of Meckel's cartilage and that muscle tissues influence mandible morphology.

PMID- 15156402
TI  - Expression pattern of VEGFR-2 (Quek1) during quail development.
AB  - The growth and maintenance of the blood and lymphatic vascular systems is to a
      large extent controlled by members of the vascular endothelial growth factor
      (VEGF) family via the tyrosine kinase receptors (VEGFRs) expressed in
      angioblastic cells. Here, we analyzed the Quek1 (VEGFR-2) expression pattern by
      whole mount in situ hybridization during quail development. During early
      embryogenesis, Quek1 expression was detected at the caudal end of the blastoderm
      and primitive streak and in the head paraxial mesoderm. In somites, expression
      was observed from HH-stage 9 onwards in the dorsolateral region of both the
      forming and recently formed somites. During somite maturation, expression
      persists in the lateral portion of the somitic compartments, the dermomyotome and
      the sclerotome. Additionally, a second expression domain in the maturing somite
      was observed in the medial part of the sclerotome adjacent to the neural tube.
      This expression domain extended medially and dorsally and surrounded the neural
      tube during later stages. In the notochord, expression was observed from HH-stage
      23 onwards. In the limb bud, expression was initiated in the mesenchyme at HH
      stage 17. During organogenesis, expression was detected in the pharyngeal arches
      and in the anlagen of the esophagus, trachea, stomach, lungs, liver, heart and
      gut. Expression was also seen in feather buds from day 7 onwards. Our results
      confirm the angiogenic potential of the mesoderm and suggest that VEGFR-2
      expressing cells represent multiple pools of mesodermal precursors of the
      hematopoietic and angiopoietic lineages.

PMID- 15156403
TI  - The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage
      disposal?
AB  - The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) is
      an intriguing protein with multiple ligands and multiple functions. Approximately
      90 - 95 % of the receptor is located intracellularly, with 5 - 10 % being on the
      cell surface. It has long been known to play an essential intracellular role in
      the transport of newly-synthesized lysosomal enzymes from the trans-Golgi network
      (TGN) to the lysosomes. More recently, however, the loss of this receptor has
      been described in some tumour types, suggesting that it may play a role in tumour
      suppression. The focus has therefore shifted to elucidating the role played by
      the cell surface receptor and its interaction with its diverse ligands in tumour
      growth and progression. The list of ligands is continuously increasing and
      includes growth factors such as IGF-II and transforming growth factor beta
      (TGFbeta). This review will address the question of whether the M6P/IGF-IIR plays
      a direct role in tumour suppression or merely plays an indirect role as a
      transporter for ligands designated for degradation in the lysosomes.

PMID- 15156404
TI  - 17beta-estradiol prevents blood-brain barrier disruption induced by VEGF.
AB  - We performed this study to determine how pretreatment of the ovariectomized rats
      with 17beta-estradiol could affect blood-brain barrier disruption caused by the
      vascular endothelial growth factor (VEGF), an important mediator of vascular
      permeability. Ovariectomized female rats aged twelve to fourteen weeks were used
      in the study. A 500 micro g 17beta-estradiol 21-day release pellet was implanted
      in the 17beta-estradiol group, and a vehicle pellet was implanted in the control
      group 21 days before the experiments. We performed three craniotomies under
      isoflurane anesthesia to expose cerebral cortices. Normal saline, 10 (- 10)M and
      10 (- 9)M VEGF patches were applied on each hole for 30 min. The transfer
      coefficient (Ki) of (14)C-alpha-amino isobutyric acid and volume of (3)H-dextran
      (70,000 dalton) distribution were determined to measure the degree of BBB
      disruption. Ki was increased by 108 % and 138 % with 10 (- 10)M and 10 (- 9)M
      VEGF respectively after VEGF application in the control group (p < 0.01).
      However, there was no significant increase in the Ki with the VEGF application in
      the 17beta-estradiol group, and their values were significantly lower than the
      corresponding data of the control group (10 (- 10)M: - 55 %, 10 (- 9)M: - 52 %, p
      <0.05). The volume of dextran distribution in the control group increased by 47 %
      with VEGF 10 (- 9)M (p < 0.05), whereas there was no significant change in the
      volume of dextran distribution with VEGF application in the 17beta-estradiol
      group and the volume was lower than the corresponding volume of the vehicle
      treated control group (10 (- 10)M: - 34 %, 10 (- 9)M: -32 %, p < 0.05). In
      conclusion, our study demonstrated that chronic 17beta-estradiol treatment
      prevented BBB disruption induced by the VEGF in the ovariectomized rats.

PMID- 15156405
TI  - Inhibition of human breast cancer cell proliferation with estradiol metabolites
      is as effective as with tamoxifen.
AB  - The anti-estrogenic substance tamoxifen is effective in the adjuvant therapy
      applied in human breast cancer. Since it partly exhibits estrogenic activity and
      has serious side-effects, however, pure anti-estrogenic compounds are being
      sought. In our experimental study, we compared the anti-proliferative effect of
      estradiol and 13 endogenous estradiol metabolites on human breast cancer cells
      with the effect of tamoxifen. We used MCF-7 and MDA-MB 231, the well-established
      estrogen receptor-positive and -negative cell lines. 4-hydroxytamoxifen, the
      active metabolite of tamoxifen, estradiol and 13 estradiol metabolites were
      tested in concentrations ranging from 3.1 to 100 microM. Incubation time was 4
      days and cell proliferation was measured by means of the ATP chemosensitivity
      test. 4-hydroxytamoxifen showed an IC50 value of 27 microM and 18 microM in MCF-7
      and MDA-MB 231 cells, respectively. Estradiol and its metabolites were anti
      proliferative in both cell lines. A few A-ring metabolites were more effective in
      inhibiting cell proliferation than D-ring metabolites and the parent substance
      17beta-estradiol. 4-OHE1, 2-MeOE1 and 2-MeOE2 were as effective in both cell
      lines as tamoxifen. For the first time it has been demonstrated that endogenous
      estradiol metabolites are equally anti-proliferative as tamoxifen in the context
      of human breast cancer cells. Since some of these metabolites exhibit no
      estrogenic activity, they are likely to be valuable in clinical studies of
      chemoprevention and adjuvant therapy of breast cancer.

PMID- 15156406
TI  - Metabolism of D-glucose anomers in rat pancreatic islets exposed to equilibrated
      D-glucose.
AB  - This study aims at establishing the contribution of alpha- and beta-D-glucose to
      the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 -
      (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were
      incubated for 60 min at 4 degrees C in the presence of equilibrated D-glucose
      (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-glucose
      labelled with tritium on either the C (2) or C (5) of the hexose. Relative to
      their respective concentrations, (3)HOH generation from the anomers labelled with
      tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable
      to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to
      each anomer separately. The relative contributions of each anomer to the total
      generation of (3)HOH was also close to the theoretical values derived from
      mathematical models for the catabolism of D-glucose at anomeric equilibrium in
      rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and
      D-[5 - (3)H]glucose. Thus, even in islets exposed to D-glucose at anomeric
      equilibrium, the metabolic fate of alpha-D-glucose differs vastly from that of
      beta-D-glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes,
      especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D
      glucose 6-phosphate.

PMID- 15156407
TI  - Influence of chronically altered thyroid status on the activity of liver
      mitochondrial glycerol-3-phosphate dehydrogenase in female inbred lewis rats.
AB  - The activity of liver mitochondrial flavoprotein-dependent glycerol-3-phosphate
      dehydrogenase (GPDH) is considered a reliable marker of thyroid status in acute
      and short-lasting experiments. The aim of this study was to ascertain whether
      GPDH activity could also be used as an index of thyroid status during chronic
      experiments over several months. We therefore analyzed GPDH activity in liver
      mitochondria of female inbred Lewis rats with thyroid status altered for 2 to 12
      months. Hyperthyroid state was maintained by triiodothyronine (T (3)) or
      thyroxine (T (4)) administration, while methimazole was employed for inducing
      hypothyroidism. We found a seven- and three-fold increase of GPDH activity in
      female rats after T (3) or T (4) administration, respectively, compared to
      euthyroid females (8.9 +/- 2.3 nmol/min/mg protein), whereas administration of
      methimazole reduced the enzyme activity almost to one-third of the euthyroid
      values. These changes were not significantly influenced by the duration of
      hyperthyroid or hypothyroid treatment. We conclude that the level of the rat
      liver GPDH activity could serve as a useful marker for evaluation of hyperthyroid
      and hypothyroid status in chronic long-lasting experiments on female inbred Lewis
      rats.

PMID- 15156409
TI  - Remnant-like lipoprotein particles as risk factors for coronary artery disease in
      elderly patients.
AB  - Although remnant-like lipoprotein particles (RLPs) are known to be atherogenic,
      the relationship between serum RLP-cholesterol (RLP-C) level and coronary artery
      disease (CAD) has not as yet been evaluated. This clinical study was aimed at
      investigating the pathological significance of serum RLP-C among several coronary
      risk factors with a clear focus on elderly patients. We took fasting venous blood
      samples to determine lipid profiles including RLP-C from 188 patients with
      angiographically identified CAD and 68 control patients. Overall analysis showed
      that the RLP-C/HDL-C ratio was higher in both single-vessel CAD group (n = 67; p
      < 0.01) and multi-vessel CAD group (n = 121; p < 0.001) compared to controls.
      Further, multiple logistic regression analysis indicated that the diabetes, HDL-C
      and the RLP-C/HDL-C ratio could discriminate CAD patients from controls. In
      patients younger than 65 years, diabetes, HDL-C, LDL-C and the LDL-C/HDL-C ratio
      as well as the RLP-C/HDL-C ratio could discriminate CAD. In patients 65 aged
      years or older, however, diabetes, triglyceride and RLP-C as well as the RLP
      C/HDL-C ratio could discriminate CAD, whereas LDL-C and the LDL-C/HDL-C ratio
      could not. These results led us to believe that the contribution of a given risk
      factor to the development of CAD in elderly patients may be different from that
      in younger patients. In elderly patients, RLP-C rather than LDL-C was strongly
      associated with the development of CAD. Accordingly, serum RLP-C levels may serve
      as a convenient and reliable index for assessing CAD.

PMID- 15156408
TI  - Comparison of the effects of 3,5,3'-triiodothyroacetic Acid and triiodothyronine
      on goiter prevention and involution and on hepatic and skeletal parameters in
      rats.
AB  - 3,5,3'-triiodothyroacetic acid (TRIAC) has been used to suppress pituitary TSH
      secretion with reported attenuation of extrapituitary effects. We investigated
      whether equivalent doses of T (3) and TRIAC preventing the induction of goiter by
      methimazole (MMI) had a different or similar impact on peripheral tissues, such
      as liver and bone. In particular, we compared the effects of both compounds on
      the activity of the hepatic thyroid hormone-responsive enzymes, malic enzyme and
      L-glicerol-3-P dehydrogenase; bone mineral density and biochemical parameters of
      bone turnover, such as bone alkaline phosphatase (b-ALP) and the carboxy-terminal
      telopeptide region of type I collagen (beta-CTX); and the activity of thyroid
      ornithine decarboxylase (ODC). We also compared the effects of T (3) and TRIAC on
      the involution of MMI-induced goiter. Our results showed that TRIAC was more
      effective than T (3) to reduce MMI-induced goiter in a short-term goiter
      involution assay. TRIAC increased hepatic enzymes activity and beta-CTX levels, a
      parameter of bone resorption, more than T (3). However, bone mineral density was
      not altered by either treatment. Both compounds even reduced ODC activity at
      doses that were not effective at the pituitary level. These results demonstrate
      increased TRIAC hepatic and antigoitrogenic activity compared to T (3). TRIAC
      induces an imbalance in bone remodeling without affecting bone mineral density.
      Further studies are required to clarify this point.

PMID- 15156410
TI  - Association of the -514C-->T polymorphism in the hepatic lipase gene (LIPC)
      promoter with elevated fasting insulin concentrations, but not insulin
      resistance, in non-diabetic Germans.
AB  - Hepatic lipase hydrolyses triglycerides and phospholipids in all major classes of
      lipoproteins. The -514C-->T genetic variation in the hepatic lipase gene promoter
      was found to be associated with diminished lipase activity, dyslipidemia, and
      atherosclerosis. We investigated whether this polymorphism associates with
      hyperinsulinemia and insulin resistance in 535 normal glucose-tolerant Germans.
      Only in homozygous individuals (22 subjects), the T allele (frequency: 18.1 %)
      was significantly associated with elevated glucose concentrations after 120 min
      of oral glucose tolerance test (p = 0.05) and with elevated fasting
      concentrations of insulin (p = 0.03), triglycerides (p < 0.01), total and HDL
      cholesterol (p = 0.02), as determined by multivariate linear regression analysis.
      In a recessive model (C/C+C/T vs. T/T), T/T was associated with decreased insulin
      sensitivity index (p = 0.03) as calculated from oral glucose tolerance test data
      (n = 535), but not with the glucose infusion rate during hyperinsulinemic
      euglycemic clamp (n = 218). In conclusion, we have provided evidence that, among
      the metabolic parameters tested, the hepatic lipase -514C-->T gene polymorphism
      correlates with elevated fasting insulin concentrations in a German population.
      Since no corresponding difference in insulin sensitivity was seen in the clamp
      subgroup, an effect of this polymorphism on insulin clearance has to be
      considered.

PMID- 15156412
TI  - Variable onset determinants and consequences of diabetes (db/db) obesity mutation
      expression: adrenergic promotion of utero-ovarian dysfunction.
AB  - Expression of the diabetes ( db/db) genotype mutation in female C57BL/KsJ mice
      induces a complex diabetes-obesity syndrome (DOS) responsible for reproductive
      tract involution promoted by hypercytolipidemia (HCL). Current studies define the
      complex and influences of the endometabolic variables that promote reproductive
      tract involution at the time of initial db/db mutation expression onset in female
      C57BL/KsJ mice. Littermate-paired, normal ( +/?) and db/db groups were isolated
      between 2 - 4 weeks of age and tissue samples analyzed for utero-ovarian
      alterations induced by the systemic, tissue, cellular and structural consequences
      of mutation expression. Significantly elevated body weights, blood glucose
      concentrations and serum insulin levels contrasted with atrophic utero-ovarian
      indices in db/db mutants compared to +/? groups. The onset of the db/db
      expression promoted obesity and a mild hyperglycemic-hyperinsulinemic state.
      Initial db/db expression was characterized by significantly increased utero
      ovarian insulin binding without variation in membrane insulin receptor
      concentrations. However, significant elevations in tissue glucose sequestration
      rates, norepinephrine (NE) concentrations and triacylglyceride lipase activity in
      db/db groups indicated that a complex of endometabolic counter-regulatory
      influences promoted the metabolic shunting of excess glucose and triglyceride
      moieties towards hypercytolipidemic storage. The resulting DOS-promoted
      accumulation of utero-ovarian cytolipidemic pools compromised reproductive tract
      cytoarchitecture in db/db mice. The results of these studies indicate that the
      inability of utero-ovarian tissue compartments to exhibit metabolic adaptation to
      the enhanced availability, transport and cellular imbibition of extracellular
      glucose-lipid pools promotes the initial cellular compromise recognized to induce
      reproductive failure in db/db mutants.

PMID- 15156411
TI  - Dependency of the metabolic effect of sc-injected human regular insulin on intra
      abdominal fat in patients with type 2 diabetes.
AB  - Ten patients with type 2 diabetes were enrolled in an isoglycemic glucose clamp
      study to determine the impact of intra-abdominal fat, subcutaneous abdominal fat
      and total abdominal fat on the metabolic effect of a single bolus (0.2 IU/kg) of
      sc-injected human regular insulin. The maximum metabolic effect associated highly
      and negatively with intra-abdominal fat (r = - 0.72, p < 0.02) and with the
      homeostasis model assessment insulin resistance score (HOMA, r = - 0.71, p <
      0.03). Likewise, the total metabolic effect of sc-injected insulin correlated
      strongly and negatively with intra-abdominal fat (r = - 0.77, p < 0.01), HOMA (r
      = - 0.74, p < 0.02) and HbA (1c) (r = - 0.70, p < 0.03). Stepwise multiple
      regression analyses showed that the highest metabolic effect was only
      significantly predicted by intra-abdominal fat, indicating a high negative
      correlation with the maximum effect (beta = - 0.72) whereas time to maximum
      metabolic effect showed a strong (beta = 0.72) and positive correlation with
      HOMA. In combination with the HOMA, it is intra-abdominal fat, and not
      subcutaneous abdominal fat, which explains 50 - 75 % of the variability of the
      effect of sc human regular insulin in patients with type 2 diabetes.

PMID- 15156413
TI  - The role of nitric oxide in the development of diabetic angiopathy.
AB  - Diabetic angiopathy is the main cause of morbidity and mortality in patients with
      diabetes mellitus. Clinical manifestations and pathophysiological mechanisms of
      diabetic angiopathy can be traced back to the development of endothelial cell
      dysfunction with alterations in the eNOS/NO system production or availability as
      the primum movens in its natural history. Hyperglycemia per se or through the
      accumulation of AGEs, increased oxidative stress, leading to NOS uncoupling and
      NO-quenching by excess superoxide and peroxynitrite, and individual genetic
      background are thought to be responsible for this NO metabolism imbalance. The
      complex interplay of these mechanisms results in a perturbation of the
      physiological properties of NO in the maintenance of endothelial homeostasis,
      such as vasodilation, anticoagulation, leukocyte adhesion, smooth muscle cell
      proliferation, and antioxidant capacity. Hence, abnormality in NO availability
      results in generalized accelerated atherosclerosis, hyperfiltration,
      glomerulosclerosis, tubulointerstitial fibrosis and progressive decline in
      glomerular filtration rate, and apoptosis and neovascularization in the retina.
      Indeed, the parallel development of nephropathy, retinopathy, and macroangiopathy
      may be considered as manifestations of endothelial dysfunction at distinct
      vascular sites. Given this scenario, intervention targeting any of the pathways
      involved in the NOS/NO system cascade may prove potential therapeutic targets in
      the prevention of long-term diabetic complications.

PMID- 15156415
TI  - [Following the medical service?].

PMID- 15156414
TI  - Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced
      by body mass index (BMI) but not by the presence of breast cancer.
AB  - While obesity is a known risk factor for postmenopausal breast cancer, the
      molecular mechanisms involved are unclear. Systemic levels of leptin, the product
      of the ob (obesity) gene, are increased in obese individuals (body mass index,
      BMI, over 25) and are higher in women than men. Leptin has been found to
      stimulate the growth of breast cancer cells in vitro. Our goal was to determine
      whether leptin was 1) present in nipple aspirate fluid (NAF), and 2) whether NAF
      leptin levels were associated with a) levels in serum, b) obesity, and c) breast
      cancer. We collected and evaluated NAF specimens from 83 subjects and serum
      specimens from 49 subjects. NAF leptin was detectable in 16/41 (39 %) of
      premenopausal and 21/42 (50 %) postmenopausal subjects. NAF leptin was
      significantly lower (p = 0.042) in premenopausal than postmenopausal women with a
      BMI < 25, but not in those with a higher BMI. NAF leptin was significantly
      associated with BMI in premenopausal (p = 0.011) but not in postmenopausal women.
      Serum leptin was associated with BMI in both premenopausal and postmenopausal
      women (p = 0.0001 for both). NAF and serum leptin were associated in
      premenopausal (p = 0.02) but not postmenopausal women. Neither NAF nor serum
      leptin was associated with premenopausal or postmenopausal breast cancer. Our
      findings include that 1) leptin is present in the breast and detectable in a
      subset of NAF samples, 2) NAF leptin in premenopausal but not postmenopausal
      women parallels serum leptin levels, and 3) neither NAF nor serum levels of
      leptin were associated with premenopausal or postmenopausal breast cancer.

PMID- 15156416
TI  - [Intensive care within the context of military long-distance transport].
AB  - Due to the changed task spectrum of the German Federal Armed Forces with
      participation in international deployments for UN and NATO the concept of
      Aeromedical Evacuation (MedEvac) gained a new quality for the Air Force as well
      as for the Medical Corps. The transport of mostly severely injured or critically
      ill patients requires both, medical equipment which has to be permanently adapted
      to the national standard, and qualified intensive-care-personnel. At present, the
      aircrafts used for such deployments are four C-160 Transall, one CL-601
      Challenger and two Airbus A310, which, if necessary, can be equipped with one or
      more intensive-care "patient transportation units" (PTU). Contrary to the two
      other aircrafts, the CL-601 Challenger is only equipped for the intensive-care
      transport of one individual patient. The PTU corresponds to the technical
      equipment of the intensive care unit of a level-1-trauma centre and ensures an
      intensive-care therapy on highest level also during longer transportation. The
      work with this equipment, the characteristics of the long-distance air transport
      and the special situation of the military deployment causes special demands on
      the qualifications of the assigned personnel. Primarily planned for the
      repatriation of injured or ill soldiers, in the mean time, this concept is also
      essential for the medevac of civilian victims after mass casualties worldwide.

PMID- 15156417
TI  - [Adam hammer (1818 - 1878) - remarks on a forgotten pioneer of ether anaesthesia
      in obstetrics].
AB  - Adam Hammer, born in 1818, and working as a doctor for the poor since 1847 in
      Mannheim, was the first person in the German speaking world to use ether for pain
      relief during labor on February 18th 1847. He took part in the abortive April
      1848 Revolution in Mannheim - a pinnacle of German liberalism and later of
      political radicalism, which attented to abolish the Monarchy and introduce a
      democratic Republic. After the revolution was put down, Hammer emigrated to the
      United States and settled down in St. Louis, Missouri. Remaining politically
      active, he joined the Republican Party, founded in 1854 and served as a military
      surgeon in the Union Army during the American Civil War. Even before the war, he
      was engaged in efforts to improve the level of medical training in America and
      was involved with the foundation of High Schools which offered training courses
      along the lines of German universities. His ideas and innovations were not
      introduced immediately, but had a significant impact on medical training
      methology later on in the US. During a visit in Europe in 1876, he was the first
      to diagnose a coronary thombosis as the cause of a heart attack on a live
      patient. The diagnosis was later confirmed by post-morten autopsy on the patient.
      In 1877 he returned to Germany and died one year later. The biography of Adam
      Hammer mirrows that of many other German-Americans whose emigration proved to be
      a gain for America but a loss for Germany. This story was destinated to be
      repeated in terrible circumstances some decades later.

PMID- 15156418
TI  - [Anaesthesia in cataract surgery for elderly people].
AB  - OBJECTIVE: In the cataract surgery the problems of anaesthesia in ophthalmo
      surgery and anaesthesia in elderly people are combined. For this patients we
      compared intravenous anaesthesia with balanced anaesthesia in cardiac and
      circulatory side effects (security), patients satisfaction and costs. METHODS: In
      a prospective, randomised study we compared in 52 (26 vs. 26) elderly patients
      (ASA II and III, mean age 78.7 +/- 8.6 years) undergoing a cataract operation
      cardiac and circulatory side effects, recovery time and patients satisfaction
      with the either type of anaesthesia by a score from 1 = best to 6 = worse and the
      occurrence of nausea/vomiting (controlled 24 h). The difference in costs were
      measured by the hospital management. RESULTS: Cardiac and circulatory side
      effects with hypotonic reactions were similar in both groups (TIVA 18 = 69.2 %/BA
      20 = 76.9 %). Hypertonic reactions were mainly seen in BA (Tiva 1.9 %, BA 69.2
      %/p < 0,001). There was no problem in the treatment of these side-effects. The
      frequency of postoperative nausea and vomiting was lower (but not significantly)
      in the TIVA group (TIVA 8 %/ BA 27 %) than in the BA group (7 and 4). The
      recovery times were shorter (p < 0.001) in TIVA, those patients were staying 24
      (+/- 6.70) minutes in the post operative unit vs. 59 (+/- 28.83) minutes in BA.
      Patients satisfaction was better in the TIVA-group (1.65) than in the patients
      treated with BA. In the calculation of costs there was a disadvantage in BA.
      CONCLUSIONS: This study showed, that in respect of cardiac and respiratory side
      effects TIVA and BA are safe methods in anaesthesia for elderly people in
      ophthalmic surgery. Nevertheless, because of shorter recovery-times, lower
      incidence of hypertonic reactiones, more patients satisfaction and lower costs
      TIVA had better results in this study. We have to ask for the evaluation of
      economy in anaesthesia that not only prices of medicaments but the complete costs
      of the cases have to be calculated.

PMID- 15156419
TI  - [Is ginger a relevant antiemetic for postoperative nausea and vomiting?].
AB  - OBJECTIVE: Ginger (Zingiber officinale) has traditionally been used in China for
      gastrointestinal symptoms, including nausea and vomiting. A recent systematic
      review on the possible antiemetic effect of ginger for various indications,
      including PONV, morning sickness, and motion sickness, concluded that ginger was
      a promising antiemetic herbal remedy, but the clinical data were insufficient to
      draw firm conclusions. Since that publication, additional data has accumulated
      and thus an updated meta-analysis was performed. METHODS: A systematic search of
      the literature was performed using different search strategies in MEDLINE,
      EMBASE, and the Cochrane Library. Six randomized controlled trials including 538
      patients were identified investigating ginger to prevent postoperative nausea and
      vomiting (PONV). Data on the incidences of PONV, nausea, vomiting, and the need
      for rescue antiemetics within the first 24 postoperative hours were extracted and
      the pooled relative risk and the numbers needed to treat (NNT) were calculated
      using a random effects model. RESULTS: The pooled relative risk to suffer from
      PONV after pre-treatment with ginger was 0.84 (95 %-confidence interval 0.69 -
      1.03). About 11 patients must be treated with ginger for one additional patient
      remaining free from PONV (NNT: 11; 95 %-CI: 6 - 250). Results for nausea,
      vomiting, and need for antiemetic rescue treatment are similar. CONCLUSION:
      Ginger is not a clinically relevant antiemetic in the PONV setting.

PMID- 15156420
TI  - [SNAP-index and bispectral index during induction of anaesthesia with propofol
      and remifentanil].
AB  - OBJECTIVE: Measurement of "depth of anesthesia" is of enormous interest to the
      anesthesiologist. New monitor systems, based on the electroencephalogram (EEG)
      were developed. The aim of the present study was to compare the SNAP index and
      the Bispectral index during induction of anesthesia with propofol and
      remifentanil. METHODS: After IRB approval and written informed consent we
      investigated 19 female patients during minor gynecologic surgery. Target
      controlled infusion (TCI) of propofol was increased in a step-by-step mode (0.5
      micro g/kg) every 1 min until the patients lost response to the modified
      Observer's Assessment of Alertness/Sedation scale (MOAAS). 5 min after the
      patient lost response remifentanil 0.4 micro g/kg/min was started. Every 20 s
      SNAP index, BIS, spectral edge frequency, mean arterial blood pressure, heart
      rate and MOASS were recorded. Prediction probability ( P(K)) was used to analyze
      the relationship of MOAAS, TCI propofol, and all investigated parameters. Changes
      after start of remifentanil were analyzed with Friedman and Wilcoxon test.
      RESULTS: SNAP index ( P(K) = 0.91) and BIS ( P(K) = 1.0) were able to distinguish
      reliably between MOAAS = 5 and MOAAS = 0. Start of remifentanil infusion resulted
      in statistically significant changes for all parameters except the SNAP index (p
      > 0,05). CONCLUSIONS: SNAP index and BIS were reliable parameters to distinguish
      different levels of sedation, but SNAP index was not able to reflect the
      analgesic potency of remifentanil during propofol infusion.

PMID- 15156421
TI  - [Malposition of a central venous catheter in a patient with severe chest trauma].
AB  - The placement of a central venous catheter is associated with specific risks
      including malposition of the catheter. We report the case of a 32 year old man
      who suffered from a severe thoracic trauma including haematopneumothorax on his
      left side. In the emergency room a large-bore central venous catheter was placed
      in the left subclavian vein, after blood had been aspirated successfully. Later,
      the haemodynamic state of the patient deteriorated, so that cardiopulmonary
      resuscitation had to be started. While great amounts of blood transfusions were
      applied via the catheter using a rapid transfusion device, the blood loss over
      the left sided chest tube increased rapidly. Emergency thoracotomy was performed,
      revealing that the catheter was not in intravenous position, but in intrapleural
      malposition. Haematothorax was caused by a laceration of the upper lobe of the
      left lung with severe bleeding from great vessels. This case shows that
      successful aspiration of blood does not exclude malposition of a central venous
      catheter. Correct position of the catheter must be verified using appropriate
      methods including chest X-ray, intracardiac ECG tracing or display of the central
      venous pressure curve on a monitor.

PMID- 15156422
TI  - [Anaesthesia in orthopedics and traumasurgery].

PMID- 15156425
TI  - Community-based interventions for marginalized populations.

PMID- 15156426
TI  - Developing a directly administered antiretroviral therapy intervention for HIV
      infected drug users: implications for program replication.
AB  - Directly administered antiretroviral therapy (DAART) is one approach to improving
      adherence to among human immunodeficiency virus (HIV)-infected drug users. We
      evaluated the essential features of a community-based DAART intervention in a
      randomized, controlled trial of DAART versus self-administered therapy. Of the
      initial 72 subjects, 78% were racial minorities, and 32% were women. Social and
      medical comorbidities among subjects included homelessness (35% of subjects),
      lack of interpersonal support (86%), major depression (57%), and alcoholism
      (36%). At baseline, the median CD4+ cell count was 403 cells/mL and the median
      HIV-1 RNA load was 146,333 copies/mL (log10 5.31 copies/mL). During the prior 6
      months, 33% of subjects had missed a medical appointment, and 47% had visited an
      emergency department. Although most subjects (67%) preferred to take their own
      medications, 76% would accept DAART if it were made compulsory. A methadone
      clinic was the DAART venue acceptable to the fewest subjects (36%), and a mobile
      syringe-exchange program was acceptable to the most subjects (83%). Adherence was
      higher for supervised than for unsupervised medication administration (P<.0001),
      a finding that supports use of daily supervision of once-daily regimens.
      Moreover, DAART should incorporate enhanced elements such as convenience,
      flexibility, confidentiality, cues and reminders, responsive pharmacy and medical
      services, and specialized training for staff.

PMID- 15156427
TI  - The feasibility of a community-based directly administered antiretroviral therapy
      program.
AB  - Improved treatment-adherence support programs are needed to help human
      immunodeficiency virus (HIV)-infected persons comply with complex highly active
      antiretroviral treatment (HAART) regimens. In an experimental directly
      administered antiretroviral therapy (DAART) program, treatment-naive and
      treatment-experienced persons who experienced failure of no more than 1 prior
      regimen were recruited from 3 public HIV/AIDS clinics in Los Angeles County. For
      6 months, trained community workers observed ingestion of 1 of 2 daily HAART
      doses, 5 days per week, and questioned the patient about the second dose, which
      enabled intense adherence monitoring and real-time intervention. From November
      2001 through November 2003, there were 67 DAART patients enrolled (69% Latino,
      21% African American, and 9% white; 63% with annual income of <10,000 dollars).
      Preliminary findings show that a DAART program based in 3 public HIV/AIDS clinics
      was feasible in a low-income urban population. Effective communication between
      the DAART staff, the medical providers, and the pharmacy is essential for the
      successful implementation of this program.

PMID- 15156429
TI  - Addressing the need for treatment paradigms for drug-abusing patients with
      multiple morbidities.
AB  - Persons who use and abuse drugs are at risk for multiple morbidities that involve
      addiction, bloodborne infectious diseases, and sexually transmitted diseases, in
      addition to psychiatric illness and social instability. Infectious diseases
      acquired as a result of drug use can diffuse into non-drug using populations
      through other high-risk behaviors. Drug users also have substantial comorbidities
      from noncommunicable diseases and complications that can affect virtually every
      organ system in the body. Diagnosis of comorbidities and complications associated
      with drug abuse usually occurs late in the disease course, particularly for
      persons who are disenfranchised and have limited or no access to medical care.
      Medical management of these comorbid conditions constitutes a significant
      challenge. Directly observed therapy (DOT) can be useful but needs to conform to
      the needs of the targeted treatment population for full efficacy. DOT may have
      its greatest impact with drug users destabilized by cocaine or methamphetamine
      use but has yet to be fully investigated in this patient population.

PMID- 15156428
TI  - Modified directly observed therapy for the treatment of HIV-seropositive
      substance users: lessons learned from a pilot study.
AB  - Highly active antiretroviral therapy (HAART) can dramatically decrease human
      immunodeficiency virus (HIV) load in plasma, increase CD4+ cell counts, and
      prolong life for HIV-seropositive persons. However, the need for optimal
      adherence has been recognized. We implemented a pilot community-based program of
      directly observed therapy (DOT) with HAART among persons with substance use
      disorders and a history of failure of HAART. A near-peer outreach worker
      initially delivered and observed once-daily HAART doses on up to 7 days per week.
      Many participants tapered the frequency of visits. Participants were assessed by
      a brief questionnaire and determination of their CD4+ cell count and plasma HIV
      load. Twenty-five HIV-seropositive persons were enrolled and followed-up for a
      mean of 6.6 months (standard deviation, 3.9 months). We found that once-daily
      dosing of HAART by DOT is feasible in this population; in addition to observation
      of the majority of doses, most participants achieved virus suppression and felt
      favorably about the intervention. Tapering the intensity of visits with maximum
      flexibility was necessary to enhance the acceptability of the program to
      participants.

PMID- 15156432
TI  - Modeling the impact of modified directly observed antiretroviral therapy on HIV
      suppression and resistance, disease progression, and death.
AB  - A simulation model that used Markov assumptions with Monte Carlo uncertainty
      analysis was evaluated 1500 times at 10,000 iterations. Modified directly
      observed therapy (MDOT) for human immunodeficiency virus was assumed to improve
      adherence to therapy to 90% of prescribed doses. The impact of MDOT interventions
      on modeled biological and clinical outcomes was compared for populations with
      mean rates of adherence (i.e., the mean percentage of prescribed doses taken by
      each member of the population who had not discontinued therapy) of 40%, 50%, 60%,
      and 70%. MDOT reduced the risk of virological failure, development of
      opportunistic infections, and death, yet increased the risk of drug resistance,
      for each adherence distribution among persons with detectable plasma virus loads.
      Over 1500 trials, for a population with 50% adherence to therapy and a 12-month
      period, MDOT increased the median rate of virological suppression from 13.2% to
      37.0% of patients, decreased the rate of opportunistic infection from 5.7% to
      4.3% of patients, and decreased the death rate from 2.9% to 2.2% of patients. In
      the same population, however, MDOT increased the rate of new drug resistance
      mutations from 1.00 to 1.41 per person during the 12-month period. The impact of
      MDOT was smaller in populations with higher levels of adherence. MDOT
      interventions will likely improve clinical outcomes in populations with low
      levels of adherence but may not be effective at preventing drug resistance in
      treatment-experienced populations. MDOT may be more effective in preventing drug
      resistance with potent regimens in treatment-naive patients.

PMID- 15156431
TI  - Directly administered antiretroviral therapy in an urban methadone maintenance
      clinic: a nonrandomized comparative study.
AB  - Methadone-maintenance treatment clinics are strategically appealing sites for
      provision of directly administered antiretroviral therapy (DAART) to human
      immunodeficiency virus type 1 (HIV-1)-infected injection drug users (IDUs). We
      initiated an ongoing DAART protocol at a university-associated methadone clinic
      in April 2001, which continues to enroll participants. Participants ingested
      antiretroviral medications under direct supervision on days they attended the
      clinic; evening doses and doses on "methadone take-home days" were self
      administered. Comparison IDUs receiving either standard care or treatment
      adherence support were randomly selected from the population of the HIV-1 clinic
      where DAART participants received their primary care for HIV-1 infection, with
      frequency matching by sex, prior antiretroviral exposure, and receipt of
      methadone therapy. In an intention-to-treat analysis, 79% of DAART participants
      achieved HIV-1 RNA levels of <400 copies/mL by month 6 of therapy, compared with
      54% in the standard care group (P=.035) and 48% in the adherence support group
      (P=.008). The preliminary results of this study both suggest that DAART can be
      feasible and acceptable to patients in a methadone clinic setting and provide
      impetus for further study of this treatment strategy in randomized controlled
      trials.

PMID- 15156433
TI  - Utility of tuberculosis directly observed therapy programs as sites for access to
      and provision of antiretroviral therapy in resource-limited countries.
AB  - The overwhelming share of the global human immunodeficiency virus (HIV) infection
      and disease burden is borne by resource-limited countries. The explosive spread
      of HIV infection and growing burden of disease in these countries has intensified
      the need to find solutions to improved access to treatment for HIV infection. The
      epidemic of HIV infection and acquired immune deficiency syndrome (AIDS) has been
      accompanied by a severe epidemic of tuberculosis. Tuberculosis has become the
      major cause of morbidity and mortality in patients with HIV disease worldwide.
      Among the various models of provision of HIV/AIDS care, one logical but
      unexplored strategy is to integrate HIV/AIDS and tuberculosis care and treatment,
      including highly active antiretroviral therapy, through existing tuberculosis
      directly observed therapy programs. This strategy could address the related
      issues of inadequate access and infrastructure and need for enhanced adherence to
      medication and thereby potentially improve the outcome for both diseases.

PMID- 15156430
TI  - Directly observed therapy for the management of HIV-infected patients in a
      methadone program.
AB  - The objective of this prospective, observational clinical study was to evaluate
      the safety and efficacy of once-daily and twice-daily directly observed therapy
      (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing
      methadone treatment. Methadone and highly active antiretroviral therapy (HAART)
      were dispensed daily as DOT, with patients in the twice-daily HAART group self
      administering the second dose. Clinical and laboratory end points were monitored,
      along with the impact of ongoing cocaine use. We studied 54 patients coinfected
      with HIV and hepatitis C virus. At baseline, the median virus load was 111,000
      copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24
      months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice
      daily HAART group had virus loads of <400 copies/mL, regardless of ongoing
      cocaine use. Thirty-two patients required methadone dose adjustment, which was
      managed without modification of HAART. Treatment-limiting hepatic toxicity was
      rare. A DOT program of coadministered methadone and HAART can be implemented with
      good results, even for patients who continue to use cocaine.

PMID- 15156434
TI  - From directly observed therapy to accompagnateurs: enhancing AIDS treatment
      outcomes in Haiti and in Boston.
AB  - Like tuberculosis, human immunodeficiency virus (HIV) disease is associated with
      poverty and social inequalities, conditions that hamper the delivery of care.
      Like tuberculosis, treatment of HIV infection requires multidrug regimens, and
      the causative agent acquires drug resistance, which can be transmitted to others.
      A pilot project in rural Haiti introduced DOT-HAART (directly observed therapy
      with highly active antiretroviral therapy) for the care of patients with advanced
      acquired immune deficiency syndrome. A similar DOT-HAART effort was launched in
      Boston for patients with drug-resistant HIV disease who had experienced failure
      of unsupervised therapy. In both settings, community health promoters or
      accompagnateurs provide more than DOT: they offer psychosocial support and link
      patients to clinical staff and available resources. DOT-HAART in these 2 settings
      presents both challenges and opportunities. These models of care can be applied
      to other poverty-stricken populations in resource-poor settings.

PMID- 15156435
TI  - Use of pharmacodynamic end points in the evaluation of gatifloxacin for the
      treatment of acute maxillary sinusitis.
AB  - The relationship between drug exposure and the time course of antimicrobial
      effect at the primary infection site for acute maxillary sinusitis has not
      previously been explored. This single-center, open-label study quantified the
      time course of sinus sterilization, described gatifloxacin exposure at the
      infection site, and posed the hypothesis that the use of continuous and
      quantitative time-related end points may allow for better characterization of
      drug effect with fewer patients than traditional clinical trial approaches. Of
      the 12 enrolled patients, 10 were clinically evaluable, from whom 7 pathogens
      were isolated: 4 Streptococcus pneumoniae, 2 staphylococci, and 1 Enterobacter
      aerogenes. The median predicted 24-h area under the curve (AUC) in sinus
      aspirates and plasma samples was 54.7 mg x h/L and 30.1 mg x h/L, respectively.
      The median 24-h AUC ratio for sinus aspirates and plasma samples was 1.51 (range,
      0.88-2.23). For patients infected with pneumococci, the median time to sinus
      sterilization was 50 h. The use of quantitative time-related end points may be
      useful in evaluating the efficacy of antimicrobial agents with fewer patients.

PMID- 15156436
TI  - Effect of ribavirin on the plasma viral DNA load in patients with disseminating
      adenovirus infection.
AB  - Adenovirus (AdV) infections are an increasingly frequent and potentially fatal
      complication in allogeneic stem cell transplant recipients. To determine the
      antiviral potential of ribavirin in an unbiased way, 4 patients without immune
      recovery were prospectively analyzed by quantitative measurement of plasma AdV
      DNA load. Administration of ribavirin at the first signs of AdV dissemination was
      not accompanied by a decrease in the plasma AdV DNA load in any of these
      patients, and an increase in the AdV load was even documented in 3. These
      observations question the potential of ribavirin to improve the outcome for
      patients with disseminating AdV infection and support a critical evaluation of
      antiviral treatments for AdV infection that involves the kinetics of virus DNA
      load as an objective parameter of viral replication.

PMID- 15156437
TI  - Meta-analysis of cephalosporins versus penicillin for treatment of group A
      streptococcal tonsillopharyngitis in adults.
AB  - We conducted a meta-analysis of 9 randomized controlled trials (involving 2113
      patients) comparing cephalosporins with penicillin for treatment of group A beta 
      hemolytic streptococcal (GABHS) tonsillopharyngitis in adults. The summary odds
      ratio (OR) for bacteriologic cure rate significantly favored cephalosporins,
      compared with penicillin (OR,1.83; 95% confidence interval [CI], 1.37-2.44); the
      bacteriologic failure rate was nearly 2 times higher for penicillin therapy than
      it was for cephalosporin therapy (P=.00004). The summary OR for clinical cure
      rate was 2.29 (95% CI, 1.61-3.28), significantly favoring cephalosporins
      (P<.00001). Sensitivity analyses for bacterial cure significantly favored
      cephalosporins over penicillin in trials that were double-blinded and of high
      quality, trials that had a well-defined clinical status, trials that performed
      GABHS serotyping, trials that eliminated carriers from analysis, and trials that
      had a test-of-cure culture performed 3-14 days after treatment. This meta
      analysis indicates that the likelihood of bacteriologic and clinical failure in
      the treatment of GABHS tonsillopharyngitis is 2 times higher for oral penicillin
      than for oral cephalosporins.

PMID- 15156438
TI  - Are cephalosporins superior to penicillin for treatment of acute streptococcal
      pharyngitis?

PMID- 15156439
TI  - Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of
      mycobacterial diseases.
AB  - Aminoglycoside use is limited by ototoxicity and nephrotoxicity. This study
      compared the incidences of toxicities associated with 2 recommended dosing
      regimens. Eighty-seven patients with tuberculosis or nontuberculous mycobacterial
      infections were prospectively randomized by drug to receive 15 mg/kg per day or
      25 mg/kg 3 times per week of intravenous streptomycin, kanamycin, or amikacin.
      Doses were adjusted to achieve target serum concentrations. The size of the
      dosage and the frequency of administration were not associated with the
      incidences of ototoxicity (hearing loss determined by audiogram), vestibular
      toxicity (determined by the findings of a physical examination), or
      nephrotoxicity (determined by elevated serum creatinine levels). Risk of
      ototoxicity (found in 32 [37%] of the patients) was associated with older age and
      with a larger cumulative dose received. Vestibular toxicity (found in 8 [9%] of
      the patients) usually resolved, and nephrotoxicity (found in 13 [15%] of the
      patients) was mild and reversible in all cases. Subjective changes in hearing or
      balance did not correlate with objective findings. Streptomycin, kanamycin, and
      amikacin can be administered either daily or 3 times weekly without affecting the
      likelihood of toxicity.

PMID- 15156441
TI  - Strategies to reduce the devastating costs of early childhood diarrhea and its
      potential long-term impact: imperatives that we can no longer afford to ignore.

PMID- 15156440
TI  - Pathogen-specific risk factors and protective factors for acute diarrheal illness
      in children aged 12-59 months in Sao Paulo, Brazil.
AB  - Diarrheal diseases are a leading cause of childhood morbidity and mortality in
      Latin America. Most studies have focused on infants but not on older children. We
      enrolled 505 children (age, 12-59 months) with diarrhea and age-matched controls
      in a case-control study in Sao Paulo, Brazil. Independent risk factors for
      diarrhea included another household member with diarrhea (matched odds ratio
      [mOR], 8.1; attributable fraction [AF], 0.17; P<.001) and consumption of homemade
      juice (mOR, 1.8; AF, 0.10; P=.01); protective factors included boiling of the
      baby bottle or nipple (mOR, 0.60; AF, 0.19; P=.026), childcare at home (mOR,
      0.58; AF, 0.12; P=.004), and piped sewage (mOR, 0.58; AF, 0.05; P=.047). Hand
      washing by the caretaker after helping the child defecate protected against
      Shigella infection (mOR, 0.35; P<.05). Preparation of rice, beans, or soup in the
      morning and serving it to children after noon were associated with
      enterotoxigenic Escherichia coli infection (mOR, 8.0; P<.05). In these poor
      households, 28% of cases of diarrhea in 1-4-year-old children was attributable to
      easily modifiable exposures.

PMID- 15156442
TI  - Risk factors for postoperative mediastinitis due to methicillin-resistant
      Staphylococcus aureus.
AB  - Risk factors for developing postoperative mediastinitis (POM) due to methicillin
      resistant Staphylococcus aureus (MRSA) were analyzed in a case-case control study
      of patients who underwent median sternotomy during the period from 1994 through
      2000. Three patient groups were studied. The first consisted of 64 patients with
      POM due to MRSA; the second consisted of 79 patients with POM due to methicillin
      susceptible S. aureus (MSSA); and the third consisted of 80 uninfected control
      patients. In multivariable analysis, patients who were diabetic (adjusted OR,
      2.86; 95% CI, 1.22-6.70), female (OR, 2.70; 95% CI, 1.25-5.88), and >70 years old
      (OR, 3.43; 95% CI, 1.53-7.71) were more likely to develop POM due to MRSA. In
      contrast, the only independent risk factor associated with POM due to MSSA was
      obesity (OR, 2.49; 95% CI, 1.25-4.96). Antimicrobial prophylaxis consisted
      primarily of cephalosporin antibiotics (administered to 97% of the patients).
      Changes in perioperative antimicrobial prophylaxis, in addition to other
      interventions, should be considered for prevention of POM due to MRSA in
      targeted, high-risk populations.

PMID- 15156443
TI  - Preventing methicillin-resistant Staphylococcus aureus infections in
      cardiovascular surgery patients: can we do any better?

PMID- 15156444
TI  - Quinolone-resistant Haemophilus influenzae in a long-term care facility: clinical
      and molecular epidemiology.
AB  - We describe a clonal outbreak of quinolone-resistant Haemophilus influenzae
      (QRHI) from an affiliated long-term care facility (LTCF-A); the outbreak was
      associated with the clinical use of levofloxacin, which was determined to be a
      risk factor for acquisition of QRHI. The minimum inhibitory concentration to
      which 90% of isolates were susceptible (MIC90), as determined by broth
      microdilution, was >4 microg/mL for levofloxacin, >2 microg/mL for moxifloxacin,
      >2 microg/mL for gatifloxacin, and 8 microg/mL for gemifloxacin. The MIC90, as
      determined by Etest (AB Biodisk), was >32 microg/mL for levofloxacin,
      ciprofloxacin, moxifloxacin, and gatifloxacin. Having been a resident at LTCF-A
      and having chronic obstructive pulmonary disease were significant risk factors
      for acquisition of QRHI at our 500-bed hospital (New York Hospital Queens). All
      QRHI isolates were found to be genetically related by pulsed-field gel
      electrophoresis, were nontypeable, were susceptible to ceftriaxone and
      azithromycin, and were negative for beta -lactamase production. Emphasis on
      patient contact and respiratory isolation and placing colonized or infected
      patients in cohorts yielded a marked reduction in the prevalence of QRHI at LTCF
      A.

PMID- 15156446
TI  - Clinical significance of Roseomonas species isolated from catheter and blood
      samples: analysis of 36 cases in patients with cancer.
AB  - This report analyzes 36 cases of bacteremia or catheter-related infection caused
      by Roseomonas species, a group of pink, slimy, waterborne, gram-negative
      coccobacilli. The causative species included the newly described Roseomonas
      mucosa (22 cases [61%]) and Roseomonas gilardii subspecies rosea (8 cases [22%])
      and known species R. gilardii subspecies gilardii (5 cases [14%]) and Roseomonas
      genomospecies 4 (1 case [3%]). Twenty-nine (81%) of the cases were symptomatic,
      with fever being the most common symptom (in 27 [75%] of the cases). Twenty (56%)
      of the infections were monomicrobic. Six cases (17%) involved persistent catheter
      colonization, and 5 of these cases required removal of the catheter to clear the
      infection. All infections resolved, most with empirical antibiotic treatment. A
      summary of the antibiotic susceptibility pattern of these strains and other
      reported series show that Roseomonas species are consistently susceptible to
      amikacin and imipenem and frequently susceptible to ciprofloxacin and
      ticarcillin, but essentially nonsusceptible to ceftazidime and cefepime. This
      result may guide future therapy for infections due to Roseomonas species.

PMID- 15156445
TI  - Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant
      strains in asian countries: a study by the Asian Network for Surveillance of
      Resistant Pathogens.
AB  - To evaluate the clinical outcomes of pneumococcal pneumonia caused by antibiotic
      resistant strains in Asian countries, we performed a prospective observational
      study of 233 cases of adult pneumococcal pneumonia in 9 Asian countries from
      January 2000 to June 2001. Among 233 isolates, 128 (55%) were not susceptible to
      penicillin (25.3% were intermediately susceptible, and 29.6% were resistant).
      Clinical severity of pneumococcal pneumonia was not significantly different
      between antibiotic-resistant and antibiotic-susceptible groups. Mortality rates
      among patients with pneumococcal pneumonia caused by penicillin-, cephalosporin-,
      or macrolide-resistant strains were not higher than those with antibiotic
      susceptible pneumococcal pneumonia. Bacteremia and mechanical ventilation were
      significant risk factors for death, but any kind of antibiotic resistance was not
      associated with increased mortality due to pneumococcal pneumonia. Outcome of
      pneumococcal pneumonia was not significantly affected by drug resistance, and
      current antimicrobial regimens are mostly effective in the treatment of
      pneumococcal pneumonia, despite the widespread emergence of in vitro resistance.

PMID- 15156447
TI  - The use and interpretation of quasi-experimental studies in infectious diseases.
AB  - Quasi-experimental study designs, sometimes called nonrandomized, pre-post
      intervention study designs, are ubiquitous in the infectious diseases literature,
      particularly in the area of interventions aimed at decreasing the spread of
      antibiotic-resistant bacteria. Little has been written about the benefits and
      limitations of the quasi-experimental approach. This article outlines a hierarchy
      of quasi-experimental study design that is applicable to infectious diseases
      studies and that, if applied, may lead to sounder research and more-convincing
      causal links between infectious diseases interventions and outcomes.

PMID- 15156448
TI  - Viral hepatitis transmission in ambulatory health care settings.
AB  - In the United States, transmission of viral hepatitis from health care-related
      exposures is uncommon and primarily recognized in the context of outbreaks.
      Transmission is typically associated with unsafe injection practices, as
      exemplified by several recent outbreaks that occurred in ambulatory health care
      settings. To prevent transmission of bloodborne pathogens, health care workers
      must adhere to standard precautions and follow fundamental infection-control
      principles, including safe injection practices and appropriate aseptic
      techniques. These principles and practices need to be made explicit in
      institutional policies and reinforced through in-service education for all
      personnel involved in direct patient care, including those in ambulatory care
      settings. The effectiveness of these measures should be monitored as part of the
      oversight process. In addition, prompt reporting of suspected health care-related
      cases coupled with appropriate investigation and improved monitoring of
      surveillance data are needed to accurately characterize and prevent health care
      related transmission of viral hepatitis.

PMID- 15156449
TI  - Atazanavir: new option for treatment of HIV infection.
AB  - Atazanavir is a recently approved human immunodeficiency virus (HIV) protease
      inhibitor that has an important role in the treatment of both antiretroviral
      naive and antiretroviral-experienced individuals. Atazanavir (400 mg) can be
      administered once per day and requires only 2 capsules. Drug exposure can be
      safely increased with coadministration of a once-daily regimen of atazanavir (300
      mg) and ritonavir (100 mg). Atazanavir is not associated with elevations in serum
      levels of total cholesterol, low-density lipoprotein cholesterol, or
      triglycerides, potentially reducing the need for lipid-lowering agents.
      Atazanavir is associated with elevations in unconjugated bilirubin levels, which
      are usually not dose limiting. For treatment-naive patients receiving atazanavir
      who experience virologic rebound, the I50L mutation in HIV protease arises, which
      does not confer cross-resistance to other protease inhibitors. In treatment
      experienced patients with high-level resistance to other protease inhibitors,
      susceptibility to atazanavir is usually reduced, and optimal effects of
      atazanavir are seen when it is administered with ritonavir. Similar to other
      protease inhibitors, careful attention must be paid to drug interactions when
      administering atazanavir with concomitant medications.

PMID- 15156450
TI  - Extensive implementation of highly active antiretroviral therapy shows great
      effect on survival and surrogate markers in vertically HIV-infected children.
AB  - We performed a retrospective observational study of 253 children vertically
      infected with human immunodeficiency virus (1994-2001) to assess the
      effectiveness of antiretroviral therapies (ARTs) on survival and surrogate
      markers at the population level. Children were divided into 3 groups according to
      the ART protocols used during the follow-up period: calendar period (CP) 1 (1994
      1996) received combined therapy with 2 nucleoside reverse transcriptase
      inhibitors (NRTIs); CP2 (1997-1998) received implementation of highly active ART
      (HAART) with 3 drugs (NRTIs, protease inhibitors, and non-NRTIs); and CP3 (1999
      2001) received extensive HAART. The children in the CP3 group had statistically
      significant longer survival periods, lower virus load (VL), highest undetectable
      VL proportion, and highest CD4+ T cell counts. HAART is effective at the
      population level at decreasing VL, increasing CD4+ T cells, and increasing the
      survival in a higher percentage of HIV-infected children.

PMID- 15156451
TI  - Effectiveness of antiretroviral therapy after protease inhibitor failure: an
      analytic overview.
AB  - To examine effectiveness of subsequent antiretroviral therapy (ART), studies
      published during the period of 1 January 1997 through 31 May 2003 involving
      patients who had failed a protease inhibitor (PI)-containing regimen and were
      switched to another regimen were reviewed. Twelve studies describing 1197
      patients were analyzed. A total of 38% of patients had human immunodeficiency
      virus (HIV) RNA levels of <500 copies/mL at 24 weeks. After adjustment for
      baseline HIV RNA level, the rate of virologic suppression ranged from 16% for
      patients switching drugs within previously failed classes to 54% for
      nonnucleoside reverse-transcriptase inhibitor (NNRTI)-naive patients switched to
      boosted PI- and NNRTI-containing regimens. ART regimens in patients who failed a
      PI-containing regimen provided virologic suppression only in a few patients. The
      best response was seen in NNRTI-naive patients receiving NNRTI- and boosted PI
      containing regimens. New approaches are needed to achieve better suppression in
      pretreated HIV-infected patients.

PMID- 15156452
TI  - Invasive pneumococcal disease in patients infected with HIV: still a threat in
      the era of highly active antiretroviral therapy.
AB  - We studied all human immunodeficiency virus (HIV)-infected patients with invasive
      pneumococcal disease who received their diagnosis during 1996-2002 to investigate
      the incidence of this disease in the highly active antiretroviral therapy era and
      to study the influence of CD4 lymphocyte count on the clinical presentation and
      outcome of disease. The overall incidence of invasive pneumococcal disease was
      11.3 cases per 100,000 person-years in adult patients without known HIV infection
      and 677 cases per 100,000 person-years in HIV-infected patients. This incidence
      remained stable over the study period. Clinical presentation, severity of
      illness, and number of recurrent episodes were similar in patients with CD4+ cell
      counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim
      sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant
      pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%;
      P=.007). The mortality rate was high (21%).

PMID- 15156453
TI  - Predictive value of polymerase chain reaction of cerebrospinal fluid for
      detection of Epstein-Barr virus to establish the diagnosis of HIV-related primary
      central nervous system lymphoma.
AB  - Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) for detection of
      Epstein-Barr virus (EBV) DNA has been proposed as a minimally invasive method for
      establishing the diagnosis of human immunodeficiency virus-related primary
      central nervous system lymphoma (PCNSL). In a review of the operational
      characteristics of this test in our clinical practice, the positive predictive
      value of CSF PCR for EBV for establishing the diagnosis of PCNSL was only 29%. Of
      7 patients with CSF PCR positive for EBV, 2 had PCNSL, and 5 received alternative
      diagnoses (specificity, 79.1%).

PMID- 15156455
TI  - Extrameningeal complications of Neisseria meningitidis serogroup W135 infection.

PMID- 15156454
TI  - Clinical features and outcome of pediatric Neisseria meningitidis serogroup W135
      infection: a report of 5 cases.
AB  - We describe 5 pediatric cases of Neisseria meningitidis serogroup W135 infection.
      Infectious and/or reactive extrameningeal involvement was frequent. One patient
      had a persistent postmeningococcal inflammatory syndrome. Four of 5 isolates
      belonged to the clonal complex 37. The important risk of extrameningeal
      complications must be borne in mind when treating children with N. meningitidis
      W135 infection.

PMID- 15156456
TI  - Human herpesvirus type 8-associated episodic multisystem illness in an HIV
      infected patient in the absence of hemophagocytic lymphohistiocytosis.

PMID- 15156458
TI  - Topical mupirocin and catheter-related bacteremia.

PMID- 15156459
TI  - Clinical and therapeutic management of pulmonary Mycobacterium xenopi infection
      in HIV-positive patients.

PMID- 15156460
TI  - Duration of nontyphoidal Salmonella carriage in asymptomatic adults.

PMID- 15156462
TI  - Pneumococcal arthritis associated with primary peritonitis in a patient with
      chronic hepatitis C infection.

PMID- 15156463
TI  - Lipoatrophy is the predominant presentation of HIV-associated lipodystrophy in
      southern India.

PMID- 15156464
TI  - Efficacy of albendazole ointment on cutaneous larva migrans in 2 young children.

PMID- 15156465
TI  - Published rather than proposed definitions for invasive fungal infection must be
      applied to allow standardization in clinical trials.

PMID- 15156466
TI  - Exophiala jeanselmei infection in a heart transplant recipient successfully
      treated with oral terbinafine.
AB  - An immunosuppressed heart transplant recipient developed Exophiala jeanselmei
      infection on the second toe. After unsuccessful treatment with different
      antifungal drugs, the infection responded to a high-dose regimen of oral
      terbinafine (an antifungal agent not yet approved in the United States for use
      against the dematiaceous fungi) and warm packs. This is, to our knowledge, the
      only known case of successful terbinafine treatment of E. jeanselmei infection.

PMID- 15156467
TI  - Mycoplasma pneumoniae and asthma in children.
AB  - The aim of this prospective study of a population of children (age, 2-15 years)
      hospitalized for severe asthma was to test them for acute infection due to
      Mycoplasma pneumoniae and acute infection due to Chlamydia pneumoniae. Of 119
      patients with previously diagnosed asthma, acute M. pneumoniae infection was
      found in 24 (20%) and C. pneumoniae infection was found in 4 (3.4%) of the
      patients during the current exacerbation. Of 51 patients experiencing their first
      asthma attack, acute M. pneumoniae infection was proven in 26 (50%) of the
      patients (P<.01) and C. pneumoniae in 4 (8.3%). In the control group of 152
      children with stable asthma or rhinitis, 8 (5.2%) had M. pneumoniae infection
      (P<.005). Of the 29 patients experiencing their first asthma attack and infected
      with M. pneumoniae or C. pneumoniae, 18 (62%) had asthma recurrences but only 6
      (27%) of the 22 patients who did not have such infections had asthma recurrences
      (P<.05). M. pneumoniae may play a role in the onset of asthma in predisposed
      children and could be a trigger for recurrent wheezing.

PMID- 15156468
TI  - Antibiotics for asthma?

PMID- 15156469
TI  - Plasma exchange-associated immunoglobulin m-negative hantavirus disease after a
      camping holiday in southern france.
AB  - A 37-year-old Belgian patient presented with acute nephropathia epidemica (NE)
      shortly after a camping holiday in southern France. Unusual symptoms were initial
      noncardiogenic lung involvement, followed by severe acute renal failure, acute
      acalculous cholecystitis, presence of immunoblasts in the bone marrow, and
      hemolytic anemia, presenting as hemolytic uremic syndrome. Positive
      immunoglobulin (Ig) A and rising IgG titers against Puumala hantavirus (PUUV)
      were detected, but IgM remained negative on days 8 and 20. The results of reverse
      transcriptase-polymerase chain reaction performed on day 8 were positive for
      PUUV. This is the first report of an iatrogenically IgM-negative hantavirus case
      due to the selective removal of heavy-weight molecules during plasma exchange via
      the centrifugation technique. This is also the first report of proven NE from the
      Mediterranean part of France.

PMID- 15156470
TI  - Glycopeptides are no more effective than beta-lactam agents for prevention of
      surgical site infection after cardiac surgery: a meta-analysis.
AB  - A meta-analysis was performed to investigate whether a switch from beta-lactams
      to glycopeptides for cardiac surgery prophylaxis should be advised. Results of 7
      randomized trials (5761 procedures) that compared surgical site infections (SSIs)
      in subjects receiving glycopeptide prophylaxis with SSIs in those who received
      beta -lactam prophylaxis were pooled. Neither agent proved to be superior for
      prevention of the primary outcome, occurrence of SSI at 30 days (risk ratio [RR],
      1.14; 95% confidence interval [CI], 0.91-1.42). In subanalyses, beta-lactams were
      superior to glycopeptides for prevention of chest SSIs (RR, 1.47; 95% CI, 1.11
      1.95) and approached superiority for prevention of deep-chest SSIs (RR, 1.33; 95%
      CI, 0.91-1.94) and SSIs caused by gram-positive bacteria (RR, 1.36; 95% CI, 0.98
      1.91). Glycopeptides approached superiority to beta-lactams for prevention of leg
      SSIs (RR, 0.77; 95% CI, 0.58-1.01) and were superior for prevention of SSIs
      caused by methicillin-resistant gram-positive bacteria (RR, 0.54; 95% CI, 0.33
      0.90). Standard prophylaxis for cardiac surgery should continue to be beta
      lactams in most circumstances.

PMID- 15156471
TI  - Antibiotic prophylaxis for cardiac surgery: does the past predict the future?

PMID- 15156472
TI  - Echinacea purpurea for prevention of experimental rhinovirus colds.
AB  - A randomized, double-blind, placebo-controlled clinical trial was conducted to
      evaluate the ability of Echinacea purpurea to prevent infection with rhinovirus
      type 39 (RV-39). Forty-eight previously healthy adults received echinacea or
      placebo, 2.5 mL 3 times per day, for 7 days before and 7 days after intranasal
      inoculation with RV-39. Symptoms were assessed to evaluate clinical illness.
      Viral culture and serologic studies were performed to evaluate the presence of
      rhinovirus infection. A total of 92% of echinacea recipients and 95% of placebo
      recipients were infected. Colds developed in 58% of echinacea recipients and 82%
      of placebo recipients (P=.114, by Fisher's exact test). Administration of
      echinacea before and after exposure to rhinovirus did not decrease the rate of
      infection; however, because of the small sample size, statistical hypothesis
      testing had relatively poor power to detect statistically significant differences
      in the frequency and severity of illness.

PMID- 15156473
TI  - Laboratory-confirmed shigellosis in the United States, 1989-2002: epidemiologic
      trends and patterns.
AB  - During 1989-2002, a total of 208,368 laboratory-confirmed Shigella infections
      were reported to the Centers for Disease Control and Prevention. Shigella sonnei
      accounted for 71.7%, Shigella flexneri accounted for 18.4%, Shigella boydii
      accounted for 1.6%, and Shigella dysenteriae accounted for 0.7% of infections;
      for 7.6%, no serogroup was reported. National incidence rates ranged from 7.6
      cases per 100,000 persons in 1993 to 3.7 cases per 100,000 persons in 1999.
      Incidence rates for S. boydii, S. dysenteriae, and S. flexneri decreased over the
      14-year period by 81%, 83%, and 64%, respectively; S. sonnei rates only decreased
      by 8%. The highest rates were reported from western states (10.0 cases per
      100,000 persons) and among children 1-4 years of age (20.6 cases per 100,000
      persons). The female-male S. sonnei incidence rate ratio among 20-39-year-old
      adults decreased from 2.3 during 1989-1999 to 1.4 during 2000-2002. Approximately
      1% of isolates were from extraenteric sources; 0.25% were from blood. S. sonnei
      remains an important cause of diarrhea in the United States. Prevention efforts
      that target high-risk groups are needed.

PMID- 15156474
TI  - Perioperative blood transfusion is predictive of poststernotomy surgical site
      infection: marker for morbidity or true immunosuppressant?
AB  - To analyze risk factors for the development of adult poststernotomy surgical site
      infections (SSIs), we performed a retrospective case-control study at a tertiary
      care hospital. Case patients with poststernotomy SSI between June 1999 and
      January 2001 were matched to control subjects without poststernotomy SSI
      according to date of procedure and age. Data were collected on known SSI risk
      factors. Of 711 procedures, we identified 38 cases with SSI and 114 matched
      controls. Univariate analysis revealed that receipt of transfused blood (odds
      ratio [OR], 3.19; 95% confidence interval [CI], 1.54-6.62), diabetes (OR, 2.90;
      95% CI, 1.27-6.59), length of stay before hospitalization (OR, 1.19 per day; 95%
      CI, 1.02-1.37 per day), and American Society of Anesthesia score (OR, 2.19; 95%
      CI, 1.04-4.64) were significantly associated with SSI. Multivariate analysis
      revealed that transfusion (OR, 3.21; 95% CI, 1.41-7.31) and diabetes (OR, 3.65;
      95% CI, 1.42-9.36) were predictors for SSI. The exact role of blood transfusion
      in the pathogenesis of SSI, whether as a direct immunosuppressant or a surrogate
      marker for morbidity, remains unresolved.

PMID- 15156475
TI  - Quantifying uncertainty: physicians' estimates of infection in critically ill
      neonates and children.
AB  - To determine the diagnostic accuracy of physicians' prior probability estimates
      of serious infection in critically ill neonates and children, we conducted a
      prospective cohort study in 2 intensive care units. Using available clinical,
      laboratory, and radiographic information, 27 physicians provided 2567 probability
      estimates for 347 patients (follow-up rate, 92%). The median probability estimate
      of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work
      up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to
      20% at initiation of antibiotic treatment (P<.001). At initiation of treatment,
      predictions discriminated well between episodes subsequently classified as proven
      infection and episodes ultimately judged unlikely to be infection (area under the
      curve, 0.88). Physicians also showed a good ability to predict blood culture
      positive sepsis (area under the curve, 0.77). Treatment and testing thresholds
      were derived from the provided predictions and treatment rates. Physicians'
      prognoses regarding the presence of serious infection were remarkably precise.
      Studies investigating the value of new tests for diagnosis of sepsis should
      establish that they add incremental value to physicians' judgment.

PMID- 15156476
TI  - Getting beyond diagnostic accuracy: moving toward approaches that can be used in
      practice.

PMID- 15156477
TI  - Streptococcus bovis endocarditis and its association with chronic liver disease:
      an underestimated risk factor.
AB  - Clinical and epidemiological characteristics of Streptococcus bovis endocarditis
      were prospectively studied among 199 patients with definite endocarditis. Thirty
      patients (15.1%) had S. bovis endocarditis. Compared with patients with non-S.
      bovis endocarditis, these 30 patients were older (mean age, 58.6+/-12.4 years vs.
      46.0+/-17.0 years; P<.001) and had higher rates of bivalvular involvement (43.3%
      vs. 7.7%; P<.001), embolism (73.3% vs. 40.2%; P=.002), and diskitis (23.3% vs.
      0.6% P<.001). In patients with S. bovis biotype I (S. bovis I) endocarditis,
      advanced liver disease was present in 56.7%, compared with 15.3% of patients with
      non-S. bovis endocarditis (P<.001), and colonic adenoma was present in 46.7%. The
      in-hospital mortality rate (16.7%) was correlated with delayed diagnosis and
      advanced liver diseases. In our city, S. bovis I endocarditis is frequently
      correlated with liver diseases; diskitis may be the first sign of the disease.

PMID- 15156478
TI  - Sedation, sucralfate, and antibiotic use are potential means for protection
      against early-onset ventilator-associated pneumonia.
AB  - To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in
      patients requiring mechanical ventilation (MV), we performed a prospective cohort
      study that included 747 patients. Pneumonia was defined as a positive result for
      a protected quantitative distal sample. EOP was defined as pneumonia that
      occurred from day 3 to day 7 of MV. Eighty patients (10.7%) experienced EOP.
      Independent predictors of EOP were male sex (odds ratio [OR], 2.06; 95%
      confidence interval [CI], 1.18-3.63), actual Glasgow Coma Scale value of 6-13
      (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR,
      1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28
      7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26). Protection occurred with
      use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), beta -lactams and/or beta 
      lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation
      cephalosporins (OR, 0.33; 95% CI, 0.16-0.74). Sucralfate use and unplanned
      extubation are independent risk factors for EOP. Use of aminoglycosides, beta
      lactams/ beta-lactamase inhibitors, or third-generation cephalosporins protects
      against EOP.

PMID- 15156479
TI  - Antibiotic use and the risk of pneumonia: 20 years of studies, but where are we
      now?

PMID- 15156480
TI  - Cranberry juice and urinary tract infection.
AB  - Cranberries have long been the focus of interest for their beneficial effects in
      preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with
      antiadherence properties that prevent fimbriated Escherichia coli from adhering
      to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical
      trials have been performed testing the effects of cranberries on the urinary
      tract. However, these trials suffer from a number of limitations. Most
      importantly, the trials have used a wide variety of cranberry products, such as
      cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules,
      and they have used different dosing regimens. Further research is required to
      clarify unanswered questions regarding the role of cranberries in protecting
      against UTI in general and in women with anatomical abnormalities in particular.

PMID- 15156481
TI  - Severe acute respiratory syndrome.
AB  - The first cases of severe acute respiratory syndrome (SARS) occurred in China in
      November 2002. The agent causing this illness has been identified as a novel
      coronavirus, SARS-coronavirus. Since its introduction <1 year ago, this virus has
      infected 8098 people in 26 countries, killing 774 of them. We present an overview
      of the epidemiology, clinical presentation, diagnosis, and treatment of SARS
      based on the current state of knowledge derived from published studies and our
      own personal experience.

PMID- 15156482
TI  - Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ
      transplant recipients.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms. In
      immunocompetent hosts, they are a rare cause of disease. In immunocompromised
      hosts, disease due to NTM is well documented. Reports of NTM disease have
      increased in hematopoietic stem cell transplant (HSCT) and solid organ transplant
      (SOT) recipients. This increase may reflect increased numbers of transplants,
      intensification of immune suppressive regimens, prolonged survival of transplant
      recipients, and/or improved diagnostic techniques. The difficulty of diagnosis
      and the impact associated with infections due to NTM in HSCT and SOT recipients
      necessitates that, to ensure prompt diagnosis and early initiation of therapy, a
      high level of suspicion for NTM disease be maintained. The most common
      manifestations of NTM infection in SOT recipients include cutaneous and
      pleuropulmonary disease, and, in HSCT recipients, catheter-related infection.
      Skin and pulmonary lesions should be biopsied for histologic examination, special
      staining, and microbiologic cultures, including cultures for bacteria, Nocardia
      species, fungi, and mycobacteria. Mycobacterial infections associated with
      catheters may be documented by tunnel or blood (isolator) cultures.
      Susceptibility testing of mycobacterial isolates is an essential component of
      optimal care. The frequent isolation of NTM other than Mycobacterium avium
      complex (MAC) from transplant recipients limits the extrapolation of therapeutic
      data from human immunodeficiency virus-infected individuals to the population of
      transplant recipients. Issues involved in the management of NTM disease in
      transplant recipients are characterized by a case of disseminated infection due
      to Mycobacterium avium complex in a lung transplant recipient, with a review of
      the relevant literature.

PMID- 15156483
TI  - Financing immunizations in the United States.
AB  - Children in the United States receive immunizations through both private and
      public sectors. The federal government has supported childhood immunization since
      1963 through the Vaccination Assistance Act (Section 317 of the Public Health
      Service Act). Since 1994, the Vaccines for Children (VFC) program has provided
      additional support for childhood vaccines. In 2002, 41% of childhood vaccines
      were purchased through VFC, 11% through Section 317, 5% through state and/or
      local governments, and 43% through the private sector. The recent introduction of
      more-expensive vaccines, such as pneumococcal conjugate vaccine, has highlighted
      weaknesses in the current system. Adult immunization is primarily performed in
      the private sector. Until 1981, there was no federal support for adult
      immunization. Since 1981, Medicare has reimbursed the cost of pneumococcal
      vaccine for its beneficiaries; influenza vaccine was added in 1993. This paper
      summarizes the history of financing immunizations in the United States and
      discusses some current problems and proposed solutions.

PMID- 15156484
TI  - Primary HIV type 1 infection.
AB  - Emerging evidence suggests that early events in human immunodeficiency virus type
      1 (HIV-1) infection may play a critical role in determining disease progression.
      Although there is limited evidence on which to base medical decisions, the
      diagnosis and treatment of acute HIV-1 infection may have virologic, immunologic,
      and clinical benefits. In addition, rapid diagnosis of infection may prevent
      unknowing transmission of HIV-1 during a period of high-level viremia. We review
      the basic principles of primary HIV-1 infection, clinical and diagnostic markers
      of acute seroconversion, approaches to management, and new therapeutic
      strategies.

PMID- 15156485
TI  - Anemia in HIV infection: clinical impact and evidence-based management
      strategies.
AB  - Anemia in human immunodeficiency virus (HIV)-infected patients can have serious
      implications, which vary from functional and quality-of-life decrements to an
      association with disease progression and decreased survival. In 2002, 16 members
      of the Anemia in HIV Working Group, an expert panel of physicians involved in the
      care of HIV-infected patients that met first in 1998, reconvened to assess new
      data and to translate these data into evidence-based treatment guidelines. The
      group reached consensus on the prevalence of anemia in the highly active
      antiretroviral therapy era; the risk factors that are independently associated
      with the development of anemia; the impact of anemia on quality of life, physical
      functioning, and survival; the impact of the treatment of hepatitis C virus
      coinfection on anemia in HIV-infected patients; evidence-based guidelines for
      treatment of anemia in HIV-infected patients, including the therapeutic role of
      epoetin alfa; and directions for future research.

PMID- 15156486
TI  - Factors associated with severe impact of lipodystrophy on the quality of life of
      patients infected with HIV-1.
AB  - A standardized questionnaire was used to assess the impact of lipodystrophy (LD)
      on quality of life (QoL). Eighty-four consecutive asymptomatic human
      immunodeficiency virus type 1 (HIV-1)-infected outpatients with clinical LD
      completed a modified version of the Dermatology Life Quality Index (DLQI) survey
      to measure the impact of body fat changes on their QoL. Body changes influenced
      dressing for 55 patients (65%), produced feelings of shame for 41 (49%), and
      disrupted sexual life for 23 (27%). There was a greater impact on the DLQI due to
      body changes among women, injection drug users, patients with abdominal or breast
      lipoaccumulation, and patients with a high number of non-LD side effects.
      Multivariate proportional odds model analysis showed that the severity of non-LD
      associated side effects and the presence of breast lipoaccumulation were
      associated with impaired psychosocial functioning. Specific characteristics of
      patients, antiretroviral-based side effects, and breast lipoaccumulation exert a
      greater impact on QoL in HIV-1-infected patients with LD.

PMID- 15156487
TI  - Impact of chronic hepatitis B virus (HBV) infection on outcomes of patients
      infected with HIV in an area where HBV infection is hyperendemic.
AB  - Between June 1994 and February 2003, a total of 111 human immunodeficiency virus
      (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387
      HIV-infected patients without HBV or hepatitis C virus coinfection were
      prospectively observed to assess the impact of HBV infection on outcomes of HIV
      infected patients. After a median duration of observation of 25 months,
      coinfected patients were more likely to develop hepatitis (adjusted hazard ratio
      [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation
      (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar
      proportions of the 2 patient groups had an increase in the CD4 count by > or
      =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new
      opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had
      an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death
      (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was
      initiated.

PMID- 15156488
TI  - Hepatitis A and B vaccination practices for ambulatory patients infected with
      HIV.
AB  - Few studies exist of adherence to guidelines for vaccination of persons infected
      with human immunodeficiency virus (HIV), especially in the era of highly active
      antiretroviral therapy (HAART). In a retrospective, cross-sectional analysis in
      the HIV Outpatient Study sites, 198 (32.4%) of 612 patients eligible for
      hepatitis B vaccine received at least 1 dose. In multivariate analysis, hepatitis
      B vaccination was associated with HIV risk category, education level, and number
      of visits to the HIV clinic per year. Among 716 patients eligible for hepatitis A
      vaccine, 167 (23.3%) received > or =1 dose. Response to hepatitis B vaccination
      was associated with higher nadir CD4+ cell counts (P=.008) and HIV RNA levels
      less than the level of detection (P=.04), although some response was documented
      at all CD4+ levels. Although there were low rates of complete hepatitis
      vaccination in this cohort of ambulatory patients, prompt efforts to vaccinate
      patients entering care, receipt of antiretroviral therapy, and practice reminder
      systems may enhance vaccination practices.

PMID- 15156490
TI  - High resolution anoscopy findings for men who have sex with men: inaccuracy of
      anal cytology as a predictor of histologic high-grade anal intraepithelial
      neoplasia and the impact of HIV serostatus.
AB  - We compared the pathological diagnoses obtained by anal Papanicolaou (Pap) smear
      with those obtained by anal biopsy or by surgical excision for 153 men who have
      sex with men (MSM). Analysis of these paired specimens showed that anal Pap
      smears were an inaccurate predictor of high-grade anal dysplasia, regardless of
      human immunodeficiency virus (HIV) serostatus. The presence of any abnormal anal
      cytological finding indicates a potential for high-grade dysplasia on
      histological examination of MSM.

PMID- 15156489
TI  - Safety of discontinuation of maintenance therapy for disseminated histoplasmosis
      after immunologic response to antiretroviral therapy.
AB  - We performed a prospective observational study to assess the safety of stopping
      maintenance therapy for disseminated histoplasmosis among human immunodeficiency
      virus infected patients after response to antiretroviral therapy. All subjects
      received at least 12 months of antifungal therapy and 6 months of antiretroviral
      therapy before entry. Negative results of fungal blood cultures, urine and serum
      Histoplasma antigen level of <4.1 units, and CD4+ T cell count of >150 cells/mm3
      were required for eligibility. Thirty-two subjects were enrolled; the median CD4+
      T cell count at study entry was 289 cells/mm3. No relapses of histoplasmosis
      occurred after a median duration of follow-up of 24 months. This corresponded to
      an observed relapse rate of 0 cases per 65 person-years. The median CD4+ T cell
      count at final study visit was 338 cells/mm3. Discontinuation of antifungal
      maintenance therapy appears to be safe for patients with acquired
      immunodeficiency syndrome with previously treated disseminated histoplasmosis and
      sustained immunologic improvement in response to antiretroviral therapy.

PMID- 15156491
TI  - Adverse reactions to accidental forearm injection of Bacille Calmette-Guerin
      vaccine in schoolchildren: 12-month cohort follow-up.
AB  - This study examined the natural history of reaction after accidental intradermal
      administration of bacille Calmette-Guerin (BCG) vaccine instead of purified
      protein derivative (PPD) in 226 schoolchildren. At 18 days after vaccination, a
      local reaction with a diameter of 4.5-14 mm was found in 62% of the students, and
      ulceration with discharge was found in 26.6%; corresponding rates at 120 days
      were 72.3% and 38% and at 281 days were 73% and 6%. At 345 days, 85% of the
      students had a dry scar measuring 5-14 mm in diameter, and none had ulceration or
      discharge.

PMID- 15156493
TI  - Rift Valley fever epidemic in Saudi Arabia: disconcerting epidemiological defects
      and lack of differential diagnoses and concordance in studies.

PMID- 15156492
TI  - Enterotoxin B is the predominant toxin involved in staphylococcal scarlet fever
      in Taiwan.
AB  - This study retrospectively reviewed all pediatric cases of staphylococcal scarlet
      fever (SSF) that occurred during a 10-year period in a 1400-bed tertiary medical
      center in northern Taiwan. All 20 cases of SSF occurred in previously healthy
      individuals. Skin and soft-tissue infections predominated among children from
      whom Staphylococcus aureus was isolated. Polymerase chain reaction testing was
      used to detect known staphylococcal toxin genes, and of the isolates studied,
      most (18 [90%] of 20) contained only the staphylococcal enterotoxin B. One of the
      other strains was positive for staphylococcal enterotoxin A only, and the last
      strain was positive for both staphylococcal enterotoxin G and staphylococcal
      enterotoxin I. Pulsed-field gel electrophoresis identified a small cluster of
      isolates (6 [30%] of 20) that were genetically related, but these strains came
      from epidemiologically unrelated patients during a 3-year period.

PMID- 15156494
TI  - Use of the induced sputum procedure in the investigation of smear-negative
      pulmonary tuberculosis.

PMID- 15156495
TI  - Non-organ-specific autoantibodies in children with chronic hepatitis C virus
      infection.

PMID- 15156497
TI  - Hypoglycorrhachia in herpes simplex encephalitis.

PMID- 15156499
TI  - Persistence of HIV drug resistance mutations: more clues from clinical
      observations.

PMID- 15156500
TI  - Multidrug-resistant HIV-1.

PMID- 15156501
TI  - Fatal infection of the hand due to Photobacterium damsela: a case report.
AB  - We report a case of fatal acute renal failure due to Photobacterium damsela
      infection of the hand. Although the patient received intensive medical care and
      surgical treatment, he died 8 h after arrival at the hospital. This is the first
      case of P. damsela sepsis proven by blood culture in Japan.

PMID- 15156502
TI  - Pneumonia and osteomyelitis due to Legionella longbeachae in a woman with
      systemic lupus erythematosus.
AB  - A patient with risk factors of systemic lupus erythematosus, corticosteroid use,
      and malignancy received a diagnosis of concomitant pneumonia and osteomyelitis
      caused by Legionella longbeachae. In this report, the first description of
      Legionella osteomyelitis, previous cases of extrapulmonary Legionella infection
      are detailed.

PMID- 15156503
TI  - Shapiro's syndrome: a renewed appreciation for vital signs.
AB  - Vital signs are an invaluable diagnostic tool, but in this era of modern medicine
      and expensive tests, important information obtainable at the patient's bedside is
      often overlooked. We report an unusual case, Shapiro's syndrome, in which an
      appreciation of temperature recordings was essential to diagnosis. We review this
      disorder and the thermoregulatory system.

PMID- 15156504
TI  - Rhabdomyolysis associated with dengue virus infection.
AB  - We describe 2 patients who developed rhabdomyolysis due to dengue virus
      infection. The first patient recovered with no sequelae, but the second developed
      multiple organ failure and died. Rhabdomyolysis is not well described as a
      complication of dengue virus infection and is probably underrecognized. All
      patients with severe dengue virus infection should undergo urinalysis, and serum
      creatinine kinase levels should be measured if urinalysis reveals heme.

PMID- 15156505
TI  - Electronic measurement of canine mean platelet volume.

PMID- 15156506
TI  - Fractional electrolyte excretion in adult cows: establishment of reference ranges
      and evaluation of seasonal variation.

PMID- 15156507
TI  - What is your diagnosis?

PMID- 15156508
TI  - Hematologic values of the yucatan miniature pig.
AB  - Mean values and ranges for 16 hematological parameters for healthy, young,
      sexually-mature Yucatan miniature swine are presented. No significant differences
      were observed between sexes with regard to hemograms. Comparison of observed
      values with those published in the literature for standard domestic and other
      breeds of miniature swine reveals no major differences.

PMID- 15156509
TI  - Sodium dodecyl sulfate polyacrylamide gel electrophoresis of canine urinary
      proteins for the analysis and differentiation of tubular and glomerular diseases.
AB  - A preliminary investigation was performed to evaluate the use of a new,
      noninvasive technique for the localization of canine renal lesions by
      electrophoresis of urinary proteins. Urine specimens from six clinically healthy,
      nonproteinuric dogs and 12 dogs with persistent proteinuria were examined by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). Urine
      electrophoretic patterns of proteinuric dogs were classified as glomerular (n =
      4), tubular (n = 2), or mixed (glomerular and tubular) (n = 6), based on the
      number and molecular weight of the silver-stained protein bands. Renal tissues
      from biopsies or necropsies were obtained from eight of the dogs with proteinuric
      disease. Interpretation of seven of eight electrophoretograms agreed with the
      histologic interpretation of renal lesions. We concluded SDS PAGE is a
      potentially valuable technique for detection and localization of renal lesions in
      dogs with proteinuric disease.

PMID- 15156510
TI  - Cytologic features of a meningioma in a dog.
AB  - Meningiomas are one of the most common nervous system tumors in dogs. They are
      mostly solitary, benign, intracranial tumors of the transitional type. Tentative
      diagnosis can usually be made on historical data, clinical and neurological
      signs, and radiographs, with an antemortem diagnosis confirmed by exploratory
      surgery and histologic evaluation of biopsy. The literature contains many reports
      of the gross, histological and ultrastructural morphology of canine meningiomas,
      but little on the cytologic features of these tumors. This report describes the
      cytologic appearance of an intracranial meningioma in a 9-year-old Miniature
      Schnauzer.

PMID- 15156512
TI  - What is your diagnosis?

PMID- 15156511
TI  - Evaluation of a rapid reagent strip test for blood glucose determination in
      diarrheic calves.
AB  - Sixty-three blood samples from 10 diarrheic calves were tested for glucose
      concentration by two methods. Plasma glucose concentration was measured by the
      conventional glucose-6-phosphate dehydrogenase method in the clinical laboratory,
      and the results compared to those obtained using a rapid reagent strip test for
      blood glucose concentration measurement. The rapid reagent strip test result
      could not be used to make an accurate prediction of the actual plasma glucose
      concentration as determined by the conventional method, due to the wide
      variability in actual plasma glucose concentrations corresponding to each rapid
      test result.

PMID- 15156514
TI  - Megakaryblastic leukemia in a dog.

PMID- 15156513
TI  - Hemolysis as a factor in clinical chemistry and hematology of the dog.
AB  - Serum biochemical, hemostatic, and hematologic analytes were determined by four
      laboratories on dog serum or plasmas containing increasing amounts of hemolysate.
      From the results of testing, interferographs were prepared to aid in decision
      making and to enhance visualization of the effects of hemolysis on the
      determination of the analytes. Heniktsus consistently interfered with the
      analysis of creatinine phosphokinase, lactic dehydrogenase, aspartate
      aminotransferase, lipase, and albumin, all of which appeared to increase with
      increasing hemolysis. The results for the remainder of the biochemical,
      hemostatic, and hematologic analytes varied greatly among analyzers or methods,
      rarely in a predictable manner, indicating that each laboratory should evaluate
      the effects of hemolysis on each analyzer and for each method used, in order to
      make informed decisions on the use of hemolyzed but irreplaceable samples.

PMID- 15156515
TI  - Shape changes in caprine erythrocytes exposed to chlorpromazine and lysolecithin.
AB  - Stomatocytic and echinocytic transformations of caprine erythrocytes were studied
      in vitro using chlorpromazine as a stomatocyyic agent and lysolecithin as an
      echinocytic agent. Morphologic changes in erythrocytes generally varied with the
      cell shape and the concentration of the substances used. Discoytic, triangular,
      and pear-shaped red cells common to normal goats, exhibited classical
      stomatocytic and echinocytic changes with formation of spherostomatocytes, sphero
      echinocytes, and spherocytes. In comparison, fusiform and spindle-shaped red
      cells found in certain Angora goats seemed less prone to shape changes and
      required greater concentrations of the inducing agents to effect such changes.
      Chlorpromazine at higher concentrations also inflicted localized membrane damage
      in form of tiny pits and lysolecithin likewise induced formation of fragile
      smooth or beaded filaments.

PMID- 15156517
TI  - What is your diagnosis:.

PMID- 15156516
TI  - Isolation of granulocytes and mononuclear cells from the blood of dogs, cats,
      horses and cattle.
AB  - A simple discontinuous Percoll density-gradient technique was adapted for
      isolation of granulocytes and mononuclear cells from cats, dogs, horses and
      cattle. Separation was accomplished at low speeds using a standard tabletop
      centrifuge. Cell purity was 100% for both granulocytes and mononuclear cells and
      cell viability exceeded 95%. Percent recovery of leukocytes ranged from 69 to
      83%.

PMID- 15156518
TI  - Effect of Desmopresssin in Normal Dogs and Dogs with von Willebrand's Disease.
AB  - Desmopressin acetate (DDAVP(R)), a synthetic analogue of vasopressin was slowly
      administered intravenously to 12 healthy dogs of various breeds and 10 Doberman
      Pinschers with mild-to-moderate type I von Willebrand's disease at a dose of 0.3,
      1.0 and 3.0 micro g/kg body weight. Plasma von Willebrand factor:antigen was
      measured by an electroimmunoassay prior to and 30, 60, 90, 120 and 180 minutes
      after desmopressin infusion. Desmopressin induced only very modest and
      statistically insignificant increases in von Willebrand factor in both groups. We
      conclude that the response to desmopressin as measured by circulating von
      Willebrand factor is much less pronounced in healthy dogs and in Doberman
      Pinschers with von Willebrand's disease than in humans.

PMID- 15156519
TI  - Idiopathic dyserythropoiesis in a dog.
AB  - Idiopathic dyserythropoiesis in a dog was characterized by chronic
      nonregenerative normocytic normochromic anemia, cellular marrow and abnormal
      morphology of erythroid precursors. Serum concentrations of Vitamin B(12), folate
      and iron were inconsistent with secondary causes of dyserythropoiesis. The
      disorder appeared to be distinct from myelodysplastic syndromes described
      previously.

PMID- 15156520
TI  - Serum enzyme changes in newborn calves fed colostrum.
AB  - In 10 newborn Holstein calves, which were initially bottle-fed on pooled
      colostrum, there were transient increases in several serum enzymes. Within a few
      hours, the mean serum gamma-glutamyl transferase (gammaGT), aspartate
      aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP), and
      lactate dehydrogenase (LDH) activities increased 62.5, 2.4, 2.0, 1.8 and 1.3
      fold, respectively. In two other calves given initial feeds of enzyme-free
      pasteurized milk, there were similar increases in serum enzymes, except serum
      gammaGT. Correct interpretation of serum enzyme activities in newborn calves must
      take into account the normal increases which occur after feeding colostrum. Serum
      gammaGT was the only enzyme to increase markedly as a result of its absorption
      from colostrum. The other serum enzymes are presumably released from the tissues
      of the calf. The increased activities of serum CK observed in some newborn calves
      probably resulted from trauma during birth or increased muscular activity after
      birth.

PMID- 15156522
TI  - The intravenous bile Acid loading test in the goat: determination of a procedural
      protocol and reference values.
AB  - An intravenous bile acid loading test was performed on 16 goats using various
      dosages and sampling protocols. A recently developed enzymatic bile acid assay
      provided an economical and technologically simple method for bile acid analysis.
      Intravenous injection of bile salts into goats was well tolerated. Clearance
      times were rapid. A protocol for performance of the test was suggested and a
      practical reference range for T 1/2 clearance of 4+/-1 minute was determined.
      Further investigations of this test in the assessment of liver function in the
      ruminant appear warranted.

PMID- 15156521
TI  - 'Minding our own business': veterinary clinical pathologists in industrial
      research and development.

PMID- 15156523
TI  - An hypothesis on the etio-pathogenesis of equine inflammatory joint disease.
AB  - The role of oxygen-derived free radicals is considered critical to the etio
      pathogenesis of equine inflammatory joint disease. In vivo, the superoxide
      radical in the joint may be derived either from activated polymorphonuclear
      leukocytes or from an ischemia/reperfusion cycle. In the presence of ferrous
      iron, it may generate the highly reactive hydroxyl radical (OH *). Predisposing
      factors may include synovitis, exercise-induced ischemia and minor traumatic
      injury to the joints. Unlike other inflammatory mediators, oxygen-derived free
      radicals may damage tissue directly and these reactive species could account for
      the tissue injury and insidious onset of equine exercise-induced degenerative
      joint disease.

PMID- 15156525
TI  - Natural history of idiopathic IgA nephropathy and factors predictive of disease
      outcome.
AB  - Among the numerous studies published in the last 20 years that have calculated
      the actuarial renal survival and tried to individuate the prognostic role of the
      clinical and histologic features present at the onset of the disease or the time
      of biopsy, we chose to critically analyze the results of the most valid (23
      studies). Actuarial renal survival at 10 years in adults was between 80% and 85%
      in most of the European, Asian, and Australian studies, but was lower than this
      in studies from the United States and exceeded 90% in the few studies on
      children. Concordance existed in this selected literature on the fact that
      impairment of renal function, severe proteinuria, and arterial hypertension are
      the strongest and more reliable clinical predictors of an unfavorable outcome.
      Extent of proteinuria during follow up was an even stronger predictor. In adult
      patients, a high score of the glomerular and tubulointerstitial lesions predicted
      a more rapid progression. When the single lesions were analyzed separately,
      glomerular sclerosis and interstitial fibrosis appeared to be the strongest, most
      reliable predictors of unfavorable prognosis. More controversial was the role of
      crescents and capsular adhesions.

PMID- 15156526
TI  - Pathogenesis of IgA nephropathy.
AB  - In IgA nephropathy (IgAN), there is dysregulation of the IgA response to a wide
      range of antigens. The dysregulation promotes synthesis of polymeric IgA1 (pIgA1)
      with physicochemical characteristics that favor mesangial deposition, including
      altered O-glycosylation of the hinge region. This may be the synthesis of IgA in
      the systemic compartment, which has the phenotype of mucosal IgA. There is not a
      change in IgA1 structure to an entirely abnormal form; rather, there is a shift
      that results in a proportional increase in forms of IgA1 also found in healthy
      individuals. Altered O-glycosylation could favor pIgA1 deposition by promoting
      formation of macromolecular IgA and immune complexes. Mesangial injury follows
      through interactions of pIgA1 with the cells and extracellular matrix proteins of
      the mesangium and the activation of complement. The final clinical expression of
      IgAN also depends on generic factors, including hypertension and proteinuria, and
      a fibrotic renal response. No single "IgAN gene" has been identified, and it is
      likely that multiple interacting genes will eventually prove to underlie
      susceptibility to IgAN and the risk of progressive renal disease. These new
      pathogenic insights have not yet led to new therapeutic opportunities.

PMID- 15156527
TI  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for
      IgA nephropathy.
AB  - The lengthy course of IgA nephropathy and the possibility of good outcomes
      without therapy suggest nontoxic therapies such as angiotensin-converting enzyme
      (ACE) inhibitors and angiotensin receptor blockers (ARBs.) Among patients with
      IgA nephropathy, both ACE inhibitors and ARBs reduce the transglomerular passage
      of large, but not small, molecules, reducing proteinuria. The antiproteinuric
      effects of ACE inhibitors and ARBs are probably equivalent. Dual ACE inhibitor
      ARB therapy reduces proteinuria by 54% to 73% and is more effective than either
      agent alone. To determine whether ACE inhibitors or ARBs preserve renal function
      long-term, one must rely on trials studying nondiabetic, proteinuric renal
      diseases rather than on trials specific to IgA nephropathy. Among this group of
      patients, several randomized, controlled trials, including the AIPRI trial, the
      REIN trial, and a metaanalysis of 11 randomized, controlled trials, have
      established clearly that the ACE inhibitors preserve renal function. There is no
      reason to believe that this information is not applicable to IgA nephropathy. The
      COOPERATE trial, in which 50% of the subjects had IgA nephropathy, established
      that ACE inhibitors and ARBs preserve renal function equally, and that dual ACE
      inhibitor-ARB therapy preserves renal function more effectively than either
      therapy alone. These data suggest that most individuals with proteinuric renal
      diseases, including IgA nephropathy, should be treated with ACE inhibitors and
      ARBs, ideally in combination. Polymorphisms of the angiotensinogen gene, the ACE
      gene, and the angiotensin II type I receptor gene have, so far, failed to predict
      either susceptibility to or progression of IgA nephropathy. However, the D allele
      of the ID polymorphism, particularly the DD genotype, could predict a favorable
      response to renin-angiotensin blockade.

PMID- 15156528
TI  - The role of fish oil/omega-3 fatty acids in the treatment of IgA nephropathy.
AB  - Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) have been
      reported in recent epidemiologic studies and randomized clinical trials in a
      variety of cardiovascular and autoimmune diseases. Fish and marine oils are the
      most abundant and convenient sources of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), the two major n-3 fatty acids that serve as
      substrates for cyclooxygenase and lipoxygenase pathways leading to less potent
      inflammatory mediators than those produced through the n-6 PUFA substrate,
      arachidonic acid. N-3 PUFA can also suppress inflammatory and/or immunologic
      responses through eicosanoid-independent mechanisms. Although the pathophysiology
      of IgA nephropathy is incompletely understood, it is likely that n-3 PUFA
      prevents renal disease progression by interfering with a number of effector
      pathways triggered by mesangial immune-complex deposition. In addition, potential
      targets of n-3 PUFA relevant to renal disease progression could be similar to
      those involved in preventing the development and progression of cardiovascular
      disease by lowering blood pressure, reducing serum lipid levels, decreasing
      vascular resistance, or preventing thrombosis. In IgA nephropathy, efficacy of n
      3 PUFA contained in fish oil supplements has been tested with varying results.
      The largest randomized clinical trial performed by our collaborative group
      provided strong evidence that treatment for 2 years with a daily dose of 1.8 g of
      EPA and 1.2 g of DHA slowed the progression of renal disease in high-risk
      patients. These benefits persisted after 6.4 years of follow up. With safety,
      composition, and dosing convenience in mind, we can recommend two products that
      are available as pharmaceutical-grade fish-oil concentrates, Omacor (Pronova
      Biocare, Oslo, Norway) and Coromega (European Reference Botanical Laboratories,
      Carlsbad, CA).

PMID- 15156529
TI  - Use of corticosteroids, other immunosuppressive therapies, and tonsillectomy in
      the treatment of IgA nephropathy.
AB  - Because IgA nephropathy (IgAN) was originally regarded as a benign condition, the
      indication of corticosteroids or other immunosuppressive therapies have been
      highly restricted because of potential side effects, and such drugs have been
      used for a specific subgroup of patients with IgAN, taking the risk/benefit ratio
      into consideration. During the last decade, however, with the recognition that
      the overall long-term prognosis of IgAN is a nonbenign condition, more aggressive
      treatments, including high-dose corticosteroids, various immunosuppressive
      agents, and tonsillectomy, have been used for wider subgroups of patients with
      IgAN. Moreover, recent studies have suggested that clinical remission as well as
      histopathologic regression of the nephropathy could be obtained by such
      treatments if treatment is initiated in its relatively early stage. Thus, the
      possibility has now been raised that the goal of treatment for patients with IgAN
      will shift from "slowing the progression of nephropathy" to "remission of
      nephropathy."

PMID- 15156531
TI  - Pediatric IgA nephropathies: clinical aspects and therapeutic approaches.
AB  - The pediatric IgA nephropathies are IgA nephrothapy (Berger's Disease) and Henoch
      Schonlein purpura nephritis. Both conditions are reviewed in detail with respect
      to epidemiology, clinical features, outcome, prognostic markers, and therapeutic
      approaches. For both conditions variable disease severity and outcome along with
      the lack of conclusive evidence for efficacy of treatment based on randomized
      clinical trials makes it difficult to make strong recommendations regarding
      therapy.

PMID- 15156530
TI  - Clinical presentation, natural history, and treatment of crescentic proliferative
      IgA nephropathy.
AB  - IgA nephropathy is one of the most common causes of glomerulonephritis in the
      world and is characterized histologically by the deposition of polymeric forms of
      IgA within the mesangium and in some cases along the glomerular capillary
      wall.(1) Proliferative and crescenteric forms of IgA are associated with
      nephrotic range proteinuria, accelerated hypertension, and a more rapid decline
      toward end-stage renal disease. Previous attempts to categorize the incidence and
      clinical significance of proliferative IgA nephropathy have given conflicting
      results. This is in part the result of the lack of a uniform nomenclature and the
      failure of clinical therapies to prolong renal survival in specific subgroups. In
      the present study, we performed a prospective open-label trial of pulse
      solumedrol and intravenous cyclophosphamide in 20 patients with IgA nephropathy
      and at least 10% cellular crescents or endocapillary proliferation on renal
      biopsy. Seventeen patients underwent repeat kidney biopsies after 6 months of
      therapy, and the morphologic response to treatment was assessed using a modified
      systemic lupus erythematosis (SLE) histologic activity and chronicity index
      score. To determine the long-term efficacy of intravenous cyclophosphamide on
      renal survival, the results of the treated patients were compared with 12
      untreated historical controls. Pulse solumedrol and intravenous cyclophosphamide
      effectively reduced peak serum creatinine, degree of proteinuria, the rate of
      decline in renal function, and the incidence of end-stage renal disease at 36
      months.

PMID- 15156532
TI  - Recurrent IgA nephropathy after renal transplantation.
AB  - Recurrence of the original disease is now the third most frequent cause of
      allograft loss at 10 years after transplantation in patients with underlying
      glomerulonephritis. IgA nephropathy (IgAN), the most common type of
      glomerulonephritis, histologically recurs in up to 60% of the patients. Initially
      considered to be a relatively benign phenomenon, several studies, which included
      a total of almost 1200 patients with underlying IgAN, have now established that
      after a mean follow up of 5 years, approximately 13% of the patients will exhibit
      some recurrence-related renal graft dysfunction and approximately 5% will have
      lost their graft as a result of recurrent IgAN. The only established predictor of
      graft loss is the time elapsed since renal transplantation. The risk of
      recurrence-associated graft loss increases to approximately 25% if a prior graft
      has already been lost as a result of recurrent IgAN. Whether living, related
      donor kidneys are at higher risk for recurrence is controversial. Despite all
      these issues, graft survival in patients with underlying IgAN compared with
      patients with other renal diseases is excellent. In patients with recurrent IgAN,
      no specific therapy other than optimal supportive care has been established.

PMID- 15156533
TI  - Osler was right.

PMID- 15156534
TI  - The Teratology Society 44th Annual Meeting in conjunction with the 28th Annual
      Meeting of the Neurobehavioral Teratology Society and the 17th International
      Conference of the Organization of Teratology Information Services. June 2004,
      Vancouver, British Columbia, Canada. Abstracts.

PMID- 15156541
TI  - A community-based study of depression in older people in Hefei, China--the GMS
      AGECAT prevalence, case validation and socio-economic correlates.
AB  - OBJECTIVE: Previously published studies of prevalence of depression in older
      people in China showed much variation in the results, while the pooled prevalence
      is low. In this study we used a standardised method, the Geriatric Mental State
      (GMS) to investigate the prevalence of depression in older people in China,
      validate the GMS-AGECAT depression cases and examine the relationship between
      depression and socio-economic deprivation. METHODS: 1736 subjects aged > or =65
      were recruited from Hefei city, China. They were interviewed at home by a survey
      team from Anhui Medical Universtiy using the GMS and other interviews. Their
      mental disorders were diagnosed by the Automated Geriatric Examination for
      Computer Assisted Taxonomy (AGECAT). Chinese psychiatrists re-examined depression
      cases and their controls. RESULTS: 39 depressed cases were diagnosed by the GMS
      AGECAT. Age-standardised prevalence was 2.2% (95% CI 1.5-2.9), which was about
      five-times lower than that of older people in Liverpool, UK. Agreement on
      depression diagnoses between the GMS-AGECAT and local Chinese psychiatrists was
      83.6%, with a Kappa of 0.67 (p<0.001). Depression was significantly related to
      socio-economic deprivation. CONCLUSIONS: This community-based study suggested a
      low prevalence of depression in older people in urban China. Approved training in
      the use of the GMS-AGECAT in mainland China should make it possible to carry out
      a large scale epidemiological study on depression in the Chinese elderly
      population to investigate its geographic variation and risk factors. The dose
      response relation between socio-economic deprivation and depression indicates
      that strategies for tackling inequality in depression in elderly are urgently
      needed in China.

PMID- 15156542
TI  - Clinical utility of computed tomography in the assessment of dementia: a memory
      clinic study.
AB  - OBJECTIVE: To define the influence of computed tomography (CT) on clinical
      decision-making in the outpatient evaluation of dementia. DESIGN: A case series
      in which two physicians reviewed standardised data extracted from clinical
      records, first blind to CT results, and then with CT results. Clinical decisions
      made with and without the input of CT were compared. The study was based in an
      outpatient referral centre for the assessment of memory disorders and dementia.
      The study involved 146 participants who were diagnosed with dementia after their
      first clinic visit, had Mini Mental State Examination scores >12, were aged >65
      years, and had no history of neurologic disease. RESULTS: CT impacted on
      diagnosis in an average of 12% (+/-2), and on treatment plan in 11% (+/-2) of
      cases. Physicians predicted a priori which cases CT may influence with an average
      sensitivity of 28% (+/-2), and specificity of 78.5% (+/-1.5). There was no
      statistically significant relationship between diagnostically uncertain cases and
      helpful CT scans [average chi(2) = 1.121 (+/-1.116), p = ns]. Blind to CT
      physicians appropriately identified cerebrovascular disease with an average
      sensitivity of 63% (+/-3), and specificity of 93.5% (+/-3.5). CONCLUSIONS: In the
      outpatient setting, CT may be expected to impact on diagnosis and treatment of
      dementia in 10% to 15% of cases. Memory clinic physicians recognise and treat
      cerebrovascular risk factors with reasonable sensitivity and specificity without
      the input of CT.

PMID- 15156543
TI  - Depression in dementia: a comparative and validation study of four brief scales
      in the elderly Chinese.
AB  - AIM: The study aimed to determine: (i) the diagnostic accuracy of four brief
      depression scales, the Geriatric Depression Scale (GDS), Even Briefer Assessment
      Scale for Depression (EBAS DEP), Single Question and Cornell Scale for Depression
      in Dementia (Cornell) in an elderly Chinese population with varying dementia
      severity; and (ii) which scale had the best diagnostic performance. METHOD: All
      four scales were administered to 88 elderly outpatients with dementia: 66 without
      and 22 with depression. Receiver Operating Characteristic (ROC) analysis was used
      to establish the optimal cut-off scores of the GDS, EBAS DEP and Cornell scales.
      The patients' dementia-severity was dichotomously categorized into mild and
      moderate-severe dementia, and the above analysis was repeated in both these
      groups to look at changes in the scales' diagnostic performance as dementia
      advances. RESULTS: The best diagnostic scale for detecting depression in dementia
      was the Cornell scale. Its optimal cut-off score was 6/7 (sensitivity 91.7%,
      specificity 80.0%) in the mild dementia group and 12/13 (sensitivity 70.0%,
      specificity 87.0%) in the more advanced dementia group. The optimal cut-off
      scores of the GDS and EBAS DEP also shifted to higher values when moving from the
      mild to the more advanced dementia groups, indicating the increasing difficulty
      on all these scales to detect depression with worsening cognitive impairment. The
      Single Question, however, was more robust with much less changes in its
      diagnostic parameters in both dementia cohorts: sensitivity 58.3%, specificity
      90.0% for mild dementia, and 60.0 and 84.8%, respectively, for more advanced
      dementia. CONCLUSION: An efficient strategy to diagnose depression in dementia
      amongst elderly Chinese patients is to administer the Single Question followed
      by, when necessary, the Cornell scale.

PMID- 15156545
TI  - Psychometric properties and factor structure of the Neuropsychiatric Inventory
      Nursing Home version in an elderly neuropsychiatric population.
AB  - BACKGROUND: The Neuropsychiatric Inventory (NPI) is an interview-based instrument
      designed to elicit information from an informal caregiver to evaluate behavioral
      disturbances in persons with dementia. Minor modifications of this instrument
      have produced the Neuropsychiatric Inventory-Nursing Home version (NPI-NH), a
      version specifically designed for interviewing professional care facility staff.
      The purpose of this investigation is to further understand the psychometric
      properties of the NPI-NH by examining its reliability, validity, and factor
      structure in an elderly neuropsychiatric population. METHOD: Participants were
      204 elderly inpatients from a large provincial neuropsychiatric hospital in
      British Columbia, Canada. Data were collected as part of a patient needs
      assessment project. RESULTS: The internal consistency reliability of the NPI-NH
      was alpha=0.67. An exploratory principal axis analysis with varimax rotation
      revealed five factors that accounted for 63.2% of the variance. These factors
      reflect aspects of psychiatric disturbance associated with: (a) Agitation; (b)
      Mood; (c) Psychosis; (d) Sleep/Motor Activity; and (e) Elevated Behavior.
      Convergent and discriminant validity of the five factors by correlating them with
      other behavioral measures was considered satisfactory. CONCLUSIONS: These results
      provide support for the clinical use of the NPI-NH as a screen for
      neuropsychiatric symptoms in an elderly neuropsychiatric population. However,
      additional research is encouraged to further evaluate the clinical utility of the
      NPI-NH in nursing home and inpatient geriatric settings.

PMID- 15156544
TI  - Presentations and management of Post Traumatic Stress Disorder and the elderly: a
      need for investigation.
AB  - BACKGROUND: With an aging population increasing presentations of cases of Post
      Traumatic Stress Disorder (PTSD) can be expected to old age services. While
      progress has been made in recent years in relation to the understanding and
      development of aetiological theories, classification, assessment and management
      strategies and protocols in the adult population, similar advances have lagged
      behind for the elderly. AIMS: To review the adult literature regarding PTSD and
      discuss how this might apply to an elderly population. An attempt is made to
      highlight a better awareness of the field of psychological trauma in the elderly
      in the hope of stimulating debate and research. METHOD: A review of the adult
      literature is conducted relating to classification, aetiology, demographic
      features, vulnerability, assessment, clinical management including psychotherapy
      and medications and how these may apply to the elderly. RESULTS: Little has been
      published in this field that directly relates to the elderly. The adult
      literature allows insight into understanding how PTSD may present in the elderly,
      and how they may be managed. CONCLUSIONS: Further specific research is needed in
      the elderly in order to facilitate a better understanding of PTSD that present in
      this unique population. This will lead to better clinical assessment, management
      and treatment provision.

PMID- 15156546
TI  - Childlessness and psychological well-being in Chinese older adults.
AB  - BACKGROUND: Childless older adults will increase rapidly in the coming future due
      to delayed marriage, infertility, and high divorce rate. We examined whether
      childlessness is significantly related to loneliness and depression and whether
      the effect of childlessness persisted even when other factors including gender,
      marital status, age, education, self-rated health status and financial strain
      were controlled for. METHOD: This article analyzes cross-sectional data collected
      from a representative community sample of 2003 Chinese elderly people aged 60 or
      above in Hong Kong. Respondents were interviewed in face-to-face format and data
      including socio-demographic variables, health indicators, loneliness and
      depression were obtained. RESULT: Logistic regression analyses revealed that
      childlessness was significantly related to loneliness and depression even after
      marital status, gender, age, education, self-reported health status, and
      financial strain were controlled for. CONCLUSION: The impact of childlessness on
      psychological well-being among elderly Chinese is more robust than that found in
      older Americans. Moreover, consistent with the findings of previous studies, we
      found that the effect of childlessness on psychological well-being has to be
      investigated in the context of marital status. Therefore, aged care service
      practitioners must take this risk factor into consideration in their preventive
      intervention and treatment for psychological well-being.

PMID- 15156547
TI  - Memantine enhances autonomy in moderate to severe Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia and its
      course renders patients functionally disabled. Memantine is the first drug to
      demonstrate a clinical benefit in the treatment of patients with moderately
      severe to severe AD. OBJECTIVES: Our objective was to illustrate the benefits of
      memantine on functional disability. METHODS: We classified 252 patients from a
      randomised 28-week clinical trial of memantine vs placebo according to their
      Activities of Daily Living capabilities measured by the ADCS-ADLsev scale. The
      scale was divided into two sub-scores: basic and instrumental. The relevance of
      this classification was validated by comparing clinical and socio-demographic
      parameters between the different autonomy classes (autonomous and dependent). The
      effect of memantine was estimated by using a logistic regression model on the
      autonomy status of patients at week 28, controlling for confounding factors
      (Observed Cases analysis). RESULTS: Our results showed that dependent patients (n
      = 106) had significantly longer disease duration, poorer cognition, greater
      severity, more behavioural alterations and higher total societal costs compared
      with autonomous patients (n = 146). When controlling for autonomy and severity at
      baseline, memantine-treated patients were three times more likely [Odds Ratio
      (OR) = 3.03; 95% Confidence Intervals (CI) = (1.38, 6.66)] to remain autonomous
      after 28 weeks. Analysis of the Treated Per Protocol set and the use of Last
      Observation Carried Forward analyses confirmed this finding. CONCLUSIONS:
      Memantine enhances autonomy in patients with moderately-severe to severe AD by
      increasing the probability of their remaining autonomous, therefore delaying
      transition to the dependent stage.

PMID- 15156548
TI  - Validation of short screening tests for depression and cognitive impairment in
      older medically ill inpatients.
AB  - OBJECTIVE: To investigate the criterion validity of the four-item Geriatric
      Depression Scale (GDS4) and the six-item Orientation-Memory-Concentration-test
      (OMC) against longer widely used screening instruments. METHOD: Participants were
      153 patients (aged 65 or over) admitted to four acute medical wards of a northern
      UK town. The validity of the GDS4 was determined using the 30-item geriatric
      depression scale (GDS30) as the comparator; the validity of the OMC was
      determined using the standardised mini-mental state examination (MMSE) as the
      comparator. For both screens, the area under receiver operating characteristic
      (ROC) curve was calculated in addition to the number of true and false positives
      and the sensitivity and specificity for various cut-off points. RESULTS: The area
      under ROC curve was 0.80 for the GDS4 and 0.90 for the OMC. Using a cut-off of
      0/1, the GDS4 correctly classified 78.2% of participants, using the GDS30 as the
      standard. This cut-off gave a sensitivity of 90.1% and specificity of 55.3%. With
      a cut-off of 1/2 the GDS4 correctly classified 76.8% of participants and had
      sensitivity and specificity of 78% and 74.5% respectively. The GDS4 and GDS30
      were highly correlated (rho=0.63, p < 0.0005). A cut-off of 10/11 on the OMC gave
      optimum performance. With this cut-off, it correctly classified 85.9% of
      participants, and had 85.6% sensitivity and 86.8% specificity. There was a
      significant correlation between the OMC and the SMMSE (rho = -0.827, p < 0.0005).
      CONCLUSION: The GDS4 and OMC appear to be useful instruments for screening for
      depression and cognitive impairment among older medical inpatients.

PMID- 15156550
TI  - Intentions of first-degree relatives of patients with Alzheimer's disease to seek
      a cognitive status examination.
AB  - AIMS: The aim of the present study was to examine the factors influencing
      intentions to seek a cognitive status evaluation among first-degree relatives of
      persons with Alzheimer's disease. METHODS: Phone interviews were conducted with
      93 first-degree relatives of persons with Alzheimer's disease, recruited from a
      large memory clinic. MEASURES: Intentions to seek a cognitive status examination
      were examined by asking participants to rate their willingness to seek a
      cognitive status examination during the next year and during the next five years.
      Independent variables included participants' and patients' characteristics,
      caregiving characteristics, knowledge about AD, worries about memory problems,
      and perceptions of the benefits and barriers of seeking a cognitive status
      examination. RESULTS: Overall, first-degree relatives reported only moderate
      intentions to seek a cognitive status examination. Their willingness to seek an
      examination was related to the characteristics of the first-degree relative
      (income and subjective memory), the characteristics of the patients (behavioral
      problems), the caregiving characteristics (primary caregiver), and to the
      perceptions of barriers associated with the examination. CONCLUSIONS: These
      findings stress the complexity of the decision-making process confronting first
      degree relatives regarding their intentions to seek a cognitive status
      examination, and suggest the need to provide information to reach an informed
      decision.

PMID- 15156549
TI  - Adverse effects of depression and cognitive impairment on rehabilitation
      participation and recovery from hip fracture.
AB  - OBJECTIVES: This study examines the effects of depression and cognitive
      impairment in elderly hip fracture patients receiving inpatient rehabilitation.
      Our goal was to determine whether any association of depression and cognitive
      impairment with rehabilitation outcome is accounted for by more immediate effects
      of these variables on rehabilitation participation. METHODS: We measured
      depression using the Hamilton Rating Scale for Depression (Ham-D), cognition
      using the Mini Mental State Examination (MMSE), and rehabilitation outcomes using
      the motor scale of the Functional Independence Measure (motor FIM) in a
      prospective observational study of 57 elderly rehabilitation hospital patients
      admitted to a university-affiliated, freestanding rehabilitation hospital with
      primary diagnosis of hip fracture. We also assessed rehabilitation participation,
      to determine whether this accounted for (mediated) any relationship of depression
      and cognitive impairment with rehabilitation outcome. RESULTS: Baseline Ham-D and
      MMSE scores were correlated with motor FIM efficiency-those with higher
      depressive symptoms had lower efficiency (r = -0.44, p < 0.001); similarly, those
      with more cognitive impairment had lower motor FIM efficiency (r = 0.52, p <
      0.001). Rehabilitation participation was a mediator of this association: greater
      depressive symptoms and cognitive impairment predicted poorer rehabilitation
      participation which, in turn, predicted lower motor FIM efficiency. Ham-D and
      MMSE scores were predictors of discharge location: subjects with high depressive
      symptoms and greater cognitive impairment were more likely to go to a nursing
      home or personal care home upon discharge. CONCLUSIONS: Depression and cognitive
      impairment are predictive of negative outcomes in elderly patients'
      rehabilitation from hip fracture. This effect is mediated by rehabilitation
      participation, and ratings in this area may serve as a potentially useful
      clinical and research tool for the rehabilitation environment.

PMID- 15156551
TI  - Affective disorders in older inpatients.
AB  - BACKGROUND: After dementia the group of depressive disorders is considered to be
      the second most common psychiatric disorder in the elderly. There is dispute
      regarding whether depression in the elderly differs from depression in the
      younger age groups by a longer duration of inpatient treatment, a more frequent
      occurrence of delusions, more cognitive impairment or by a more frequent co
      occurrence of physical disease. This study aimed to compare younger with older
      inpatients with respect to these aspects. METHODS: Retrospective chart review of
      all admissions to the psychiatric department of a General University Hospital
      (n=9400) and review of the documentation of 15 348 psychiatric consultations in
      the years 1990-1998. The clinical diagnoses were made according to the ICD-10
      criteria. RESULTS: 15.5% of the psychiatric inpatients in this period suffered
      from depressive episodes (ICD-10 F31.3-31.5,32,33). The proportion of depressive
      episodes increased with age, making up 5.4% in the age group below 30 years and
      37.4% in the age group of 70-79 years. On the basis of the ICD-10 criteria for
      the severity of depressive episodes no significant differences could be
      demonstrated between the younger (< 65 years) and the older inpatients (>/= 65
      years). In particular, no higher frequency of psychotic symptoms with increasing
      age could be found. The length of inpatient treatment did not significantly
      differ between both age groups. The elder patients showed less suicidal attempts
      prior to admission and less psychiatric comorbidity, but a significantly higher
      rate of concurrent physical illness. In 923 inpatients a psychiatrist was
      consulted by the other medical departments because of a co-occurrence of physical
      with affective disorders, making up 8.6% of the total seen by the psychiatric
      consultation service. Here again, the proportion of depressive episodes increased
      with age. The pattern of the depressive episodes in these patients did not differ
      from that seen in the psychiatric inpatients. LIMITATIONS: Only clinical
      diagnoses made by experienced psychiatrists were evaluated. CONCLUSIONS:
      According to our results older depressive inpatients differ from younger ones
      only with regard to concurrent comorbidity but not with respect to the duration
      of inpatient treatment or the pattern or severity of depressive symptoms. They
      more frequently suffered from physical illness but less often showed concurrent
      psychiatric comorbidity.

PMID- 15156552
TI  - Recurrent episode in three older patients suffering from chronic depression:
      positive response to TMS treatment.

PMID- 15156553
TI  - Recall of 9.11 in Alzheimer's disease: further evidence for intact flashbulb
      memory.

PMID- 15156554
TI  - Neglect of somatoform disorders.

PMID- 15156555
TI  - Preventive effects of a water-soluble derivative of chroman moiety of vitamin E
      on lipid hydroperoxide-induced cell injuries and DNA cleavages through
      repressions of oxidative stress in the cytoplasm of human keratinocytes.
AB  - ChrCrx (6-hydroxy-2, 5, 7, 8-tetramethyl-chroman-2-carboxylic acid) is a water
      soluble analog in which 4', 8', 12'-trimethyltridecyl chain is deleted from an
      alpha-tocopherol molecule known as a hydrophobic antioxidant. Cell viability of
      human skin epidermal keratinocytes HaCaT was lowered by treatment with tert
      butylhydroperoxide (t-BuOOH) of 50 microM for 48 h, designated as a subacute
      cytotoxicity, which was prevented by previous administration with ChrCrx in a
      dose-dependent manner as estimated by mitochondrial function-based WST-1 assay
      and cell morphological microscopy. In contrast an acute cytotoxicity due to
      treatment with t-BuOOH as dense as 200 microM for a period as short as 2 h could
      be also prevented with ChrCrx that was administered before and after, but was
      eliminated during, treatment with t-BuOOH. In contrast alpha-tocopherol was not
      cytoprotective against t-BuOOH. DNA strand cleavages were induced with t-BuOOH in
      the keratinocytes, and could be prevented by ChrCrx more effectively than alpha
      tocopherol as assayed by TUNEL stain. The intracellular reactive oxygen species
      (ROS) was accumulated in a manner dependent on periods of t-BuOOH treatment in
      the cytoplasm more abundantly rather than the nucleus of keratinocytes, and was
      markedly diminished by ChrCrx as shown by fluorography using the redox indicator
      dye. Thus t-BuOOH-induced cell injuries and DNA cleavages of the keratinocytes
      can be prevented at least in part through efficient diminishment of ROS generated
      in the cytoplasm, to which the preferred distribution of ChrCrx may be
      advantageous over to the nucleus or membrane owing to its molecular
      hydrophilicity relative to alpha-tocopherol.

PMID- 15156556
TI  - Vitamin D regulated keratinocyte differentiation.
AB  - The epidermis is the largest organ in the body. It is comprised primarily of
      keratinocytes which are arranged in layers that recapitulates their programmed
      life cycle. Proliferating keratinocytes are on the bottom-the stratum basale. As
      keratinocytes leave the stratum basale they begin to differentiate, culminating
      in the enucleated stratum corneum which has the major role of permeability
      barrier. Calcium and the active metabolite of vitamin D, 1,25(OH)(2)D(3), play
      important roles in this differentiation process. The epidermis has a gradient of
      calcium with lowest concentrations in the stratum basale, and highest
      concentrations in the stratum granulosum where proteins critical for barrier
      function are produced. Vitamin D is made in different layers of the epidermis,
      but 1,25(OH)(2)D(3) is made primarily in the stratum basale. Together calcium and
      1,25(OH)(2)D(3) regulate the ordered differentiation process by the sequential
      turning on and off the genes producing the elements required for differentiation
      as well as activating those enzymes involved in differentiation. Animal models in
      which the sensing mechanism for calcium, the receptor for 1,25(OH)(2)D(3), or the
      enzyme producing 1,25(OH)(2)D(3) have been rendered inoperative demonstrate the
      importance of these mechanisms for the differentiation process, although each
      animal model has its own phenotype. This review will examine the mechanisms by
      which calcium and 1,25(OH)(2)D(3) interact to control epidermal differentiation.

PMID- 15156557
TI  - The 33 kb transcript of the chicken alpha-globin gene domain is part of the
      nuclear matrix.
AB  - Giant nuclear transcripts, and in particular the RNAs of the globin gene domains
      which are much larger than their canonical pre-mRNAs, have been an enigma for
      many years. We show here that in avian erythroblastosis virus (AEV)-transformed
      chicken erythroleukaemic cells, where globin gene expression is abortive, the
      whole domain of alpha-globin genes is transcribed for about 33 kb in the globin
      direction and that this RNA is part of the nuclear matrix. Northern blot
      hybridisation with strand-specific riboprobes, recognising genes and intergenic
      sequences, and RT-PCR with downstream primers, show that the continuous full
      domain transcript (FDT) starts in the vicinity of a putative LCR and includes all
      the genes as well as known regulatory sites, the replication origin, and the DNA
      loop anchorage region in the upstream area. Absent in chicken fibroblasts, the
      globin FDT overlaps the major part of the ggPRX housekeeping gene that is
      transcribed in the opposite direction. RT-PCR and in situ hybridisation with
      genic and extra-genic globin probes demonstrated that the globin FDT is a
      component of the nuclear matrix. We suggest that the globin FDTs keep the domain
      in an active state, and the globin RNAs on the processing pathway are a component
      of the nuclear matrix. They may take part in the dynamic nuclear architecture
      when productively processed, or turn over slowly when globins are not
      synthesised.

PMID- 15156558
TI  - Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells.
AB  - Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which
      catalyzes conversion of HMG-CoA to mevalonate, a rate-limiting step in
      cholesterol synthesis. The present study was undertaken to understand the events
      of osteoblast differentiation induced by statins. Simvastatin at 10(-7) M
      markedly increased mRNA expression for bone morphogenetic protein-2 (BMP-2),
      vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen,
      bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells
      (MC3T3-E1), while suppressing gene expression for collagenase-1, and collagenase
      3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase
      digestive proteins, and noncollagenous proteins was increased in the cells
      treated with 10(-7) M simvastatin, or 10(-8) M cerivastatin. In the culture of
      MC3T3-E1 cells, statins stimulated mineralization; pretreating MC3T3-E1 cells
      with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite)
      abolished statin-induced mineralization. Statins stimulate osteoblast
      differentiation in vitro, and may hold promise drugs for the treatment of
      osteoporosis in the future.

PMID- 15156559
TI  - Human microvascular endothelial cell prostaglandin E1 synthesis during in vitro
      ischemia-reperfusion.
AB  - Ischemia-reperfusion injury is a microvascular event documented in numerous in
      vivo animal models. In animal models, prostaglandin and prostaglandin analogues
      have been found to ameliorate reperfusion injury. These studies were undertaken
      to evaluate human microvascular endothelial PGE(1) synthesis during in vitro
      ischemia followed by reperfusion. Human (neonatal) microvascular endothelial cell
      (MEC) cultures (n = 6) were subjected to sequential 2 h periods of normoxia (20%
      O(2)), ischemia (1.5% O(2)), and reperfusion (20% O(2)). Prostaglandin E(2)
      synthesis in conditioned media was determined by ELISA. Steady state levels of
      MEC prostaglandin H synthase (PGHS)-1 and -2 mRNA were assessed at the end of
      each 2-h period using RT-PCR and a quantitative mRNA ELISA. MEC PGHS protein
      levels were analyzed using an ELISA. PGE(1) release increased significantly
      during the initial 30 min of ischemia, but rapidly fell below normoxic levels by
      90 and 120 min. During reperfusion, PGE(1) release returned to normoxic levels at
      30, 60, and 90 min, and exceeded normoxic levels at 120 min. PGHS-1 mRNA levels
      were undetectable during all experimental conditions. PGHS-2 mRNA levels were
      unchanged by ischemia, but were decreased by reperfusion. In contrast, PGHS-2
      protein levels increased 3-fold during ischemia, and remained elevated during
      reperfusion. Human MEC do not express PGHS-1 mRNA in vitro. Prolonged ischemia
      decreases MEC PGE(1) synthesis, and stimulates increased PGHS-2 protein levels
      without altering the steady state levels of COX-2 mRNA. During reperfusion,
      increased PGHS-2 protein levels persist and are associated with stimulated PGE(2)
      secretion, despite relative decreases in PGHS-2 mRNA.

PMID- 15156560
TI  - Secretions of MMP-9 by soluble glucocorticoid-induced tumor necrosis factor
      receptor (sGITR) mediated by protein kinase C (PKC)delta and phospholipase D
      (PLD) in murine macrophage.
AB  - The secretion of matrix metalloproteinase (MMP-9) is stimulated by the
      glucocorticoid-induced tumor necrosis factor receptor (GITR), a new tumor
      necrosis factor receptor (TNFR) family, in murine macrophages via an activation
      of protein kinase C (PKC)delta and phospholipase D (PLD). Secretions of MMP-9 are
      stimulated by the phosphatidic acid (PA), a product of PLD activity and an
      inhibition of PA production by a 1-propanol inhibited secretion of MMP-9 by
      soluble GITR (sGITR). MMP-9 is not secreted by diacylglycerol (DAG) and an
      inhibitor of PA phosphatase has no effect on the secretion induced by sGITR,
      indicating that PA is responsible for MMP-9 secretion in murine macrophages. Our
      data indicates that sGITR-induced activation of PKCdelta and PLD increases MMP-9
      secretions in macrophages.

PMID- 15156561
TI  - Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.
AB  - Hypoxia and induction of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) is
      a hallmark of many tumors. Under normal oxygen tension HIF-alpha subunits are
      rapidly degraded through prolyl hydroxylase dependent interaction with the von
      Hippel-Lindau (VHL) tumor suppressor protein, a component of E3 ubuiquitin ligase
      complex. Using microarray analysis of VHL mutated and re-introduced cells, we
      found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with
      known HIF target genes, while the other two family members (PHD1 and 2) did not
      respond to VHL. We further tested the regulation of these genes by HIF-1 and HIF
      2 and found that siRNA targeted degradation of HIF-1alpha and HIF-2alpha results
      in decreased hypoxia-induced PHD3 expression. Ectopic overexpression of HIF
      2alpha in two different cell lines provided a much better induction of PHD3 gene
      than HIF-1alpha. In contrast, we demonstrate that PHD2 is not affected by
      overexpression or downregulation of HIF-2alpha. However, induction of PHD2 by
      hypoxia has HIF-1-independent and -dependent components. Short-term hypoxia (4 h)
      results in induction of PHD2 independent of HIF-1, while PHD2 accumulation by
      prolonged hypoxia (16 h) was decreased by siRNA-mediated degradation of HIF
      1alpha subunit. These data further advance our understanding of the differential
      role of HIF factors and putative feedback loop in HIF regulation.

PMID- 15156562
TI  - Mitogen-activated protein kinases modulate H(2)O(2)-induced apoptosis in primary
      rat alveolar epithelial cells.
AB  - Increasing evidence suggests a role for apoptosis in the maintenance of the
      alveolar epithelium under normal and pathological conditions. However, the
      signaling pathways modulating alveolar type II (ATII) cell apoptosis remain
      poorly defined. Here we investigated the role of MAPKs as modulators of oxidant
      mediated ATII cell apoptosis using in vitro models of H(2)O(2)-stress. H(2)O(2),
      delivered either as a bolus or as a flux, lead to time- and concentration
      dependent increases in ATII cells apoptosis. Increased apoptosis in primary rat
      ATII cells was detected at H(2)O(2) concentrations and production rates in the
      physiological range (1 microM) and peaked at 100 microM H(2)O(2). Immortalized
      rat lung epithelial cells (RLE), in contrast, required millimolar concentration
      of H(2)O(2) for maximal responses. H(2)O(2)-induced apoptosis was preceded by
      rapid activation of all three classes of mitogen-activated protein kinases
      (MAPKs): ERK, JNK, and p38. Specific inhibition of JNK using antisense
      oligonucleotides and ERK and p38 using PD98059 or SB202190, respectively,
      indicated a pro-apoptotic role for JNK pathway and an anti-apoptotic role for ERK
      and p38-initiated signaling events. Our data show that the balance between the
      activation of JNK, ERK, and p38 is a critical determinant of cell fate,
      suggesting that pharmacological interventions on the MAPK pathways may be useful
      in the treatment of oxidant-related lung injury.

PMID- 15156563
TI  - Cellular senescence induced by p53-ras cooperation is independent of p21waf1 in
      murine embryo fibroblasts.
AB  - Oncogenic activation in primary murine fibroblasts initiates a senescence-like
      cell cycle arrest that depends on the p53 tumor suppressor pathway. Conditional
      p53 activation efficiently induced a reversible cell cycle arrest but was unable
      to induce features of senescence. In contrast, coexpression of oncogenic ras with
      p53 produced an irreversible cell cycle arrest that displayed features of
      cellular senescence. Introduction of a conditional murine p53 allele (p53val135)
      into double p53/p21-null mouse embryonic fibroblasts showed that p21waf1 was not
      required for this effect, since p53-/-;p21-/- double-null cells undergo terminal
      growth arrest with features of senescence following coexpression of oncogenic Ras
      and p53. Our results indicate that oncogenic activation of the Ras pathway in
      murine fibroblasts converts p53 into a senescence inducer through a p21waf1
      independent mechanism.

PMID- 15156564
TI  - Differential effects of PD98059 and U0126 on osteogenesis and adipogenesis.
AB  - PD98059 and U0126 are considered as specific inhibitors of the p42/44 mitogen
      activated protein kinases (MAPK) pathway, which affects osteogenesis and
      adipogenesis. Here, we show unexpected differential effects of PD98059 and U0126
      on osteogenesis and adipogenesis as well as on estrogen (E2)-induced actions in
      osteoprogenitor KS483 cells. PD98059 dose-dependently inhibited osteogenesis
      indicated by cellular alkaline phosphatase (ALP) activity and nodule formation,
      but stimulated adipogenesis shown by the number of adipocytes. In contrast, U0126
      slightly decreased osteogenesis but had no effects on adipogenesis, although it
      inhibited p42/44 MAPK more potently than PD98059. Furthermore, PD98059, but not
      U0126, counteracted E2-induced osteogenesis and adipogenesis. Transfection
      experiments showed that PD98059, but not U0126, had estrogenic transcriptional
      activity. Interestingly, both PD98059 and U0126 potentiated E2-induced estrogenic
      transcriptional activity in KS483 cells, which is opposite to the response in
      MCF7 breast cancer cells. Our data indicate that the cross-talk between growth
      factors and estrogen receptor (ER)-mediated pathways in KS483 cells is different
      from that in MCF7 cells. In summary, the differential effects of PD98059 and
      U0126 indicate their actions are not exclusively due to an inhibition of MAPK
      pathway. Caution should be taken in the interpretation of the results obtained
      using these inhibitors.

PMID- 15156565
TI  - Phosphatase 2A is involved in endothelial cell microtubule remodeling and barrier
      regulation.
AB  - We have recently shown that microtubule (MT) inhibitor, nocodazole (2-5 microM)
      significantly increases endothelial cells (EC) actomyosin contraction and
      permeability indicating the importance of MT in maintaining the EC barrier (Verin
      et al. [2001]: Cell Mol Physiol 281:L565-L574). Okadaic acid (OA, 2-5 nM), a
      powerful inhibitor of protein phosphatase 2A (PP2A), significantly potentiates
      the effect of submaximal concentrations of nocodazole (50-200 nM) on
      transendothelial electrical resistance (TER) suggesting the involvement of PP2A
      activity in the MT-mediated EC barrier regulation. Immunofluorescent staining of
      EC revealed that in control cells PP2A distributes in a pattern similar to MT.
      Consistent with these results, we demonstrated that significant amounts of PP2A
      were present in MT-enriched EC fractions indicating tight association of PP2A
      with MT in endothelium. Treatment of EC with OA leads to disappearance of MT-like
      PP2A staining suggesting dissociation of PP2A from the MT network. Next, we
      examined the effect of PP2A inhibition on phosphorylation status of MT-associated
      protein tau, which in its unphosphorylated form promotes MT assembly. OA caused
      significant increases in tau phosphorylation confirming that tau is a substrate
      for PP2A in endothelium. Immunofluorescent experiments demonstrated that the OA
      induced increases in tau phosphorylation strongly correlated with translocation
      of phospho-tau to cell periphery and disassembly of peripheral MT. These results
      suggest the involvement of PP2A-mediated tau dephosphorylation in alteration of
      EC MT structure and highlight the potential importance of PP2A in the regulation
      of EC the MT cytoskeleton and barrier function.

PMID- 15156566
TI  - K317, R319, and E320 within the proximal C-terminus of the bradykinin B2 receptor
      form a motif important for phospholipase C and phospholipase A2 but not
      connective tissue growth factor related signaling.
AB  - We showed previously that large domain exchanges between the bradykinin B2 (BKB2)
      and angiotensin II type 1a (AT1a) receptors can result in functional hybrids.
      However, when we proceeded to exchange the entire bradykinin B2 receptor (BKB2R)
      C-terminal tail with the AT1aR C-terminus, the hybrid, while continuing to bind
      BK and be endocytosed as wild type (WT) BKB2R, lost much of its ability to
      activate phosphatidylinositol (PI) turnover or the release of arachidonic acid
      (ARA). In this study, we constructed chimeric receptors within the proximal C
      terminus between the BKB2R and AT1aR or bradykinin B1 receptor (BKB1R). The
      mutant and WT receptor cDNAs were stably transfected into Rat-1 cells. Also,
      point mutations were generated to evaluate the role of the individual residues
      within this region. These chimeric studies revealed that the proximal portion of
      the BKB2R C-tail is crucial for G protein-linked BKB2R functions. This region
      could not be swapped with the AT1aR to obtain a BK activated PI turnover or ARA
      release. Further studies demonstrated that the distal portion (325-330) of this
      region is exchangeable; however, the middle portion (317-324) is not. Small motif
      exchanges within this section identified the KSR and EVY motifs as crucial for
      G(alphaq), G(alphai) related signaling of the BKB2R. Point mutations then showed
      that the charged amino acids K317, R319, and E320 are the residues critical for
      linking to PI turnover and ARA release. However, these proximal chimeras showed
      normal receptor uptake. Interestingly, while apparently not activating G protein
      linked signaling, the proximal tail AT1aR exchange mutant and the entire C
      terminus exchange hybrid continued to cause a substantial bradykinin effected
      increase in connective tissue growth factor (CTGF) mRNA level, as WT BKB2R.

PMID- 15156567
TI  - Functional domains of APOBEC3G required for antiviral activity.
AB  - The viral protein, Vif, is essential for the production of infectious progeny
      virions in natural target cells of human immunodeficiency virus type 1 (HIV-1).
      Several recent reports indicate that Vif acts by antagonizing the activity of an
      endogenous human antiviral protein, APOBEC3G. To investigate this route to
      restrict HIV-1 infection, we employed mutagenesis to assess APOBEC3G function
      during HIV-1 infection including interaction with Vif, localization, and activity
      in virions. We found that APOBEC3G binds Vif in infected cells and the C'
      terminal region is required for this interaction. APOBEC3G was only incorporated
      into virions in the absence of Vif and deletion of either the N'-terminal or C'
      terminal regions of APOBEC3G abrogated virion localization. Assaying endogenous
      reverse transcription we found that APOBEC3G and its C'-terminal deletion mutant
      inhibited full-length cDNA synthesis, possibly through binding to viral RNA, a
      function revealed through gel-shift assays. Taken together, our studies suggest
      that APOBEC3G inhibits HIV-1 infection through interference with reverse
      transcription and that Vif counteracts APOBEC3G by impeding its entry into
      virions.

PMID- 15156568
TI  - N-myristoyltransferase inhibitor protein is homologous to heat shock cognate
      protein 70.
AB  - Many of viral and eukaryotic proteins are required for signal transduction and
      regulatory functions which undergo a lipid modification by the enzyme N
      myristoyltransferase (NMT). In this study, we demonstrated that heat shock
      cognate protein 70 (HSC70) is homologous to NMT inhibitor protein (NIP71), which
      was discovered in our laboratory, based on MALDI-TOF mass spectrometric analysis.
      The purified bovine cytosolic HSC70 and particulate NIP71 produced a dose
      dependent inhibition of human NMT having half maximal inhibitions of 235 and 230
      nM, respectively. Further, Western blot analysis revealed that the purified
      particulate NIP71 and cytosolic HSC70 cross-reacted with both anti-NIP71 and anti
      HSC70 antibodies. The results we obtained imply that molecular chaperones could
      be involved in the regulation of NMT in normal and cancerous cells. Further
      studies directed to revealing the role of HSC70 in the regulation of NMT may lead
      to the development of gene based therapies of colon cancer.

PMID- 15156569
TI  - Platelet-derived growth factor-induced arachidonic acid release for enhancement
      of prostaglandin E(2) synthesis in human gingival fibroblasts pretreated with
      interleukin-1beta.
AB  - Platelet-derived growth factor (PDGF) is a biological mediator for connective
      tissue cells and plays a critical role in a wide variety of physiological and
      pathological processes. We here investigated the effect of PDGF on arachidonic
      acid release and prostaglandin E(2) (PGE(2)) synthesis in human gingival
      fibroblasts (HGF). PDGF induced arachidonic acid release in a time- and dose
      dependent manner, and simultaneously induced a transient increase in
      intracellular Ca(2+) concentration ([Ca(2+)](i)), but less provoked PGE(2)
      release and cyclooxygenase-2 (COX-2) mRNA expression. When [Ca(2+)](i) was
      increased by Ca(2+)-mobilizing reagents, arachidonic acid release was increased.
      The PDGF-induced arachidonic acid release and increase in [Ca(2+)](i) were
      prevented by a tyrosine kinase inhibitor. On the other hand, in the HGF pre
      stimulated with interleukin-1beta (IL-1beta), PDGF clearly increased PGE(2)
      release. The PDGF-induced PGE(2) release was inhibited by a tyrosine kinase
      inhibitor. In the HGF pretreated with IL-1beta, arachidonic acid strongly
      enhanced PGE(2) release and COX-2 mRNA expression. These results suggest that
      PDGF stimulates arachidonic acid release by the increase in [Ca(2+)](i) via
      tyrosine kinase activation, and which contributes to PGE(2) production via COX-2
      expression in HGF primed with IL-1beta.

PMID- 15156570
TI  - Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid
      dehydrogenase 2.
AB  - Renal 11beta-hydroxysteroid dehydrogenase 2 (HSD2) catalyzes the conversion of
      active glucocorticoids to inert 11beta-keto compounds, thereby preventing the
      illicit binding of these hormones to mineralocorticoid receptors (MRs) and, thus,
      conferring aldosterone specificity. Absence or inhibition of HSD2 activity,
      originates a hypertensive syndrome with sodium retention and increased potassium
      elimination. Recent studies from our laboratory reported an increment of HSD2
      activity in intact-stressed rats. To evaluate the adrenal involvement in this
      increase, we analyzed HSD2 activity and protein abundance in Intact, Sham
      operated, and adrenalectomized rats under stress situations (gavage with an
      overload of 200 mM HCl (10 ml) and simulated gavage) or with corticosterone
      replacement. HSD2 activity was assessed in renal microsomal preparations obtained
      from different groups of animals. HSD2 protein abundance was measured by Western
      blot. Circulating corticosterone was determined by radioimmunoassay. Sham
      operated animals showed an increase in HSD2 activity and abundance compared to
      Intact and adrenalectomized rats suggesting the involvement of stress-related
      adrenal factors in HSD2 regulation. In the case of acidotic adrenalectomized
      animals, there was an increase in renal HSD2 activity when, along with the HCl
      overload, the rats were injected with corticosterone. This increment occurred
      without an increase in enzyme abundance. These results suggest the importance of
      circulating levels of glucocorticoids to respond to a metabolic acidosis, through
      regulation of HSD2 stimulation. The group subjected to a simulated gavage showed
      an increase in enzyme activity and protein abundance, thus demonstrating the need
      for both adrenal and extra-factors in the modulation of renal HSD2. The
      adrenalectomized animals injected with different doses of corticosterone,
      produced a progressive increase in enzyme activity and abundance, being
      significant for the dose of 68 microg corticosterone/100 g body weight. The
      highest dose (308 microg/100 g body weight) did not show any variation in
      activity and abundance compared to the control group. This biphasic effect of
      glucocorticoids could be explained taking into account their permissive and
      suppressive actions, depending on their blood levels. Knowing that stress induces
      multifactorial responses, it should not be surprising to observe a differential
      regulation in renal HSD2, confirming that different stressors act through
      different factors of both, adrenal and extra-adrenal origin.

PMID- 15156571
TI  - Neurotensin negatively modulates Akt activity in neurotensin receptor-1
      transfected AV12 cells.
AB  - Neurotensin (NT) regulates a variety of biological processes primarily through
      interaction with neurotensin receptor-1 (NTR1), a heterotrimeric G-protein
      coupled receptor (GPCR). Stimulation of NTR1 has been linked to activation of
      multiple signaling transduction pathways via specific coupling to G(q), G(i/o),
      or G(s), in various cell systems. However, the function of NT/NTR1 in the
      regulation of the Akt pathway remains unknown. Here, we report that activation of
      NTR1 by NT inhibits Akt activity as determined by the dephosphorylation of Akt at
      both Ser473 and Thr308 in AV12 cells constitutively expressing human NTR1
      (NTR1/AV12). The inactivation of Akt by NT was rapid and dose-dependent. This
      effect of NT was completely blocked by the specific NTR1 antagonist, (S)-(+)-[1
      (7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)-carbonylamino]
      cyclohexylacetic acid (SR 48527), but unaffected by the less active enantiomer
      ((R)-(-)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)
      carbonylamino] cyclohexylacetic acid (SR 49711)), indicating the
      stereospecificity of NTR1 in the negative regulation of Akt. In addition, NT
      prevented insulin- and epidermal growth factor (EGF)-mediated Akt activation. Our
      results provide insight into the role of NT in the modulation of Akt signaling
      and the potential physiological significance of Akt regulation by NT.

PMID- 15156572
TI  - Analysis of the adaptor function of the LIM domain-containing protein FHL2 using
      an affinity chromatography approach.
AB  - Containing four LIM domains and an N-terminal half LIM domain, FHL2 has been
      predicted to have an adaptor function in the formation of higher order molecular
      complexes in the nucleus and the cytoplasm of cells. We expressed recombinant
      FHL2 in insect cells using the baculovirus system and used it to isolate direct
      or indirect interaction partners from the cytosolic fraction of fibroblasts by
      affinity chromatography. These were identified by their peptide mass fingerprints
      using MALDI-TOF mass spectrometry. Cytoskeleton-associated proteins present among
      the bound proteins were shown to co-localise with FHL2 in cell lamellipodia by
      indirect immunofluorescence staining.

PMID- 15156573
TI  - ERM proteins of the lens.
AB  - Ezrin and radixin and protein 4.1 were detected in the lens of the eye. These
      proteins were mainly present in the young elongating cortical fiber cells and
      localized to the plasma membranes. Moesin was not detected. Ezrin, radixin, and
      protein 4.1 provide another means whereby actin is linked to the plasma membrane
      in addition to the known adherens junctions in the lens.

PMID- 15156574
TI  - Zinc-metallothionein genoprotective effect is independent of the glutathione
      depletion in HaCaT keratinocytes after solar light irradiation.
AB  - UV radiations are the major environmental factors that induce DNA damage of skin
      cells either by direct absorption (UVB), or after inducing an oxidative stress
      (UVA and UVB). Cells maintain a reducing intracellular environment to avoid
      genomic damage. MTs have been expected not only to control metal homeostasis but
      also counteract the glutathione (GSH) depletion induced by oxidative stress
      because of their high thiol content. Induction and redistribution of MTs in
      cultured human keratinocytes (HaCaT) in response to SSL, is an important cellular
      defense mechanism against DNA damage. Reduced glutathione (GSH) is another way of
      cellular protection against UV-induced oxidative stress. This study which extend
      our previous finding focused on the relation between intracellular GSH and Zn
      genoprotective effects after solar irradiation. HaCaT cells, depleted or not in
      GSH by a chemical treatment were used to compare MTs induction by Northern blot,
      expression by Western blot and localization using immunocytochemistry. Zn
      genoprotection experiments after SSL irradiation was carried out by the comet
      assay. We demonstrated that in absence of GSH, Zn-MTs could protect DNA after SSL
      irradiation and that GSH depletion has no effect on MTs induction and
      localization. Nuclear Zn-MTs could be responsible for this observed
      genoprotection in GSH depleted cells. So the GSH/Zn and the MT/Zn systems could
      be two independent but interacting mechanisms of cellular protection against SSL
      injury.

PMID- 15156575
TI  - Direct synaptic connections between rods and OFF cone bipolar cells in the rabbit
      retina.
AB  - Mammalian retinal circuits are broadly divided into rod and cone pathways,
      responsible for dark- and light-adapted vision, respectively. The classic rod
      pathway employs a single type of rod bipolar cell, which synapses with AII
      amacrine cells. AII amacrine cells then pass the signal to ON and OFF cone
      bipolar cells, respectively. Alternatively, rod signals may enter cones via gap
      junctions between rods and cones, and then pass from cones to cone bipolar cells.
      Thus, this second rod pathway does not utilize rod bipolar cells. Finally, in
      rodents, a third rod pathway, involving direct connections between rods and
      certain OFF cone bipolar cells, has been suggested. In this study, 56 OFF cone
      bipolar cells in the rabbit retina were dye-injected with Lucifer Yellow and
      their photoreceptor connections were examined by confocal microscopy in
      wholemount. The locations of rod and cone terminals were marked with antibodies
      to mGluR6 or synaptic proteins. Most OFF cone bipolar dendrites terminated at
      cone pedicles but some made potential contacts with rod spherules. The synaptic
      nature of these sites was confirmed by the presence of GluR2 receptors. All three
      OFF bipolar cell types had dendrites that terminated at rod spherules. However,
      approximately 80% of Ba2 and Ba3, but only 26% of Ba1 OFF cone bipolar cells made
      rod contacts. This variability suggests differential rod input to certain retinal
      pathways. In summary, we report anatomical evidence for direct connections
      between rods and OFF cone bipolar cells in a nonrodent mammal. Our data suggest
      that this alternative rod pathway may be a common feature of the mammalian
      retina.

PMID- 15156576
TI  - Postnatal development of cholinergic synapses on mouse spinal motoneurons.
AB  - Following birth, when mammals are relatively immobile, significant development of
      the motor system facilitates weight bearing and locomotion. Prominent cholinergic
      C-terminals develop on somata and proximal dendrites of spinal motoneurons during
      this time period. It is hypothesized that these terminals are essential in
      regulating motoneuron excitability and thus their development contributes to
      motor system maturation. Therefore, the development of pre- and postsynaptic
      components of the C-terminal synapse on motoneurons in mice during the early
      postnatal period was investigated. Fluorescence immunohistochemical studies
      revealed that developmental increases in punctate labeling of presynaptic
      cholinergic terminals, as visualized by vesicular acetylcholine transporter
      immunoreactivity (VAChT-IR) corresponded to the progressive expression and
      spatial restriction of immunoreactivity for the calcium channel subunit
      alpha(1)2.2 (N-type) located presynaptically and the muscarinic type 2
      acetylcholine receptor situated postsynaptically. In addition, clustering of
      immunoreactivity for the potassium channel subunit K(V)2.1 occurred within the
      early postnatal period in concert and colocalized with the maturation of the C
      terminals. The time course of development of these components of the C-terminal
      synapse corresponds to the maturation of the motor system that enables the animal
      to locomote in an adult-like fashion.

PMID- 15156577
TI  - Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system:
      Implications for regulatory activity within the hypothalamic-pituitary-adrenal
      axis.
AB  - Transient receptor potential channel proteins (TRPs) constitute a steadily
      growing family of ion channels with a range of purported functions. It has been
      demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat,
      is expressed in medium to large diameter dorsal root ganglion neurons. In this
      study, antisera specific for the human TRPV2 homologue were raised and
      characterized for immunohistochemical use. Subsequently, thorough investigation
      was made of the localization of this cation channel in the macaque primate brain.
      TRPV2-immunoreactive material was highly restrictively localized to hypothalamic
      paraventricular, suprachiasmatic, and supraoptic nuclei. Confocal double- and
      triple-labeling studies demonstrated that TRPV2 immunoreactivity is
      preferentially localized to oxytocinergic and vasopressinergic neurons. Few, if
      any, cells in these regions expressed TRPV2 immunoreactivity in the absence of
      oxytocin immunoreactivity or vasopressin immunoreactivity. Expression in the
      paraventricular and supraoptic nuclei suggests that TRPV2 is likely to play a
      fundamental role in mediating cation transport in neurohypophysial neurons. TRPV2
      has been shown to be translocated upon cell activation and neurons expressing
      TRPV2 immunoreactivity in vivo are among those known to engage in sporadic,
      intense activity. Taken together, these data suggest that this channel may play a
      vital role in mediating physiological activities associated with oxytocin and
      vasopressin release such as parturition, lactation, and diuresis. These data may
      also implicate the involvement of TRPV2 in disorders of the hypothalamic
      pituitary-adrenal axis, including anxiety, depression, hypertension, and preterm
      labor.

PMID- 15156578
TI  - Brain mapping of three somatostatin encoding genes in the goldfish.
AB  - In the present study the brain distribution of three somatostatin (SRIF)-encoding
      genes, PSS-I, PSS-II, and PSS-III, was analyzed by in situ hybridization (ISH) in
      the goldfish. The PSS-I mRNA showed the widest distribution throughout the brain,
      whereas PSS-II transcripts were restricted to some hypothalamic nuclei. On the
      other hand, PSS-III presents an intermediate distribution pattern. All SRIF
      encoding genes are expressed in hypophysiotropic nuclei supporting the idea that,
      in addition to SRIF-14, [Pro(2)] SRIF-14, and gSRIF-28 have pituitary-controlling
      functions. Moreover, each of the genes is expressed in nuclei directly associated
      with feeding behavior, suggesting a role for SRIF peptides in the central control
      of food intake and energy balance. Alternatively, they might have a role in
      processing sensory information related with feeding behavior, since PSS genes are
      expressed in the main gustatory, olfactory, and visual centers, which project to
      the hypothalamic feeding center in teleost fish.

PMID- 15156579
TI  - Postsynaptic localization of gamma-aminobutyric acid transporters and receptors
      in the outer plexiform layer of the goldfish retina: An ultrastructural study.
AB  - The gamma-aminobutyric acid (GABA)-ergic system in the outer plexiform layer
      (OPL) of the goldfish retina was studied via light and electron
      immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of
      plasma membrane GABA transporters GAT2 and GAT3, the alpha1 and alpha3 subunits
      of the ionotropic GABA(A) receptor, and the rho1 subunit of the ionotropic
      GABA(C) receptor were determined. The localization of the GAT2-IR and GAT3-IR to
      horizontal cell dendrites at the base of the cone synaptic complex was the main
      characteristic at the ultrastructural level. Very rarely, GAT2-IR and GAT3-IR
      were found in horizontal cell dendrites innervating rod spherules. alpha1-IR and
      alpha3-IR were seen in wide bands in the OPL, whereas rho1-IR appeared as a
      narrow band in the OPL. Most alpha1-IR was intracellular in rod and cone
      terminals. Membrane-associated alpha1-IR was observed in cone pedicles but not in
      rod spherules; postsynaptic elements were also labeled. alpha3-IR was
      concentrated in the lateral elements of horizontal cell dendrites in cone
      pedicles. In contrast, rho1-IR was found mainly on the spinules of the horizontal
      cell dendrites in cone pedicles. In addition, in another type of cone pedicle,
      rho1-IR was found at the position of OFF-bipolar cell dendrites. alpha3-IR and
      rho1-IR were rarely found in horizontal cell dendrites innervating rods. We
      suggest that two GABAergic pathways exist in the outer retina- first, a GABAergic
      positive loop with GABA receptors mainly on the horizontal cell dendrites and
      spinules and, second, a GABAergic feedback pathway involving GABA receptors on
      cone pedicles and GABA transporters on horizontal cells and that this pathway
      presumably modulates feedback strength from horizontal cells to cones.

PMID- 15156580
TI  - Cholinergic elements in the zebrafish central nervous system: Histochemical and
      immunohistochemical analysis.
AB  - Recently, the zebrafish has been extensively used for studying the development of
      the central nervous system (CNS). However, the zebrafish CNS has been poorly
      analyzed in the adult. The cholinergic/cholinoceptive system of the zebrafish CNS
      was analyzed by using choline acetyltransferase (ChAT) immunohistochemistry and
      acetylcholinesterase (AChE) histochemistry in the brain, retina, and spinal cord.
      AChE labeling was more abundant and more widely distributed than ChAT
      immunoreactivity. In the telencephalon, ChAT-immunoreactive (ChAT-ir) cells were
      absent, whereas AChE-positive neurons were observed in both the olfactory bulb
      and the telencephalic hemispheres. The diencephalon was the region with the
      lowest density of AChE-positive cells, mainly located in the pretectum, whereas
      ChAT-ir cells were exclusively located in the preoptic region. ChAT-ir cells were
      restricted to the periventricular stratum of the optic tectum, but AChE-positive
      neurons were observed throughout the whole extension of the lamination except in
      the marginal stratum. Although ChAT immunoreactivity was restricted to the
      rostral tegmental, oculomotor, and trochlear nuclei within the mesencephalic
      tegmentum, a widespread distribution of AChE reactivity was observed in this
      region. The isthmic region showed abundant AChE-positive and ChAT-ir cells in the
      isthmic, secondary gustatory and superior reticular nucleus and in the nucleus
      lateralis valvulae. ChAT immunoreactivity was absent in the cerebellum, although
      AChE staining was observed in Purkinje and granule cells. The medulla oblongata
      showed a widespread distribution of AChE-positive cells in all main subdivisions,
      including the octavolateral area, reticular formation, and motor nuclei of the
      cranial nerves. ChAT-ir elements in this area were restricted to the descending
      octaval nucleus, the octaval efferent nucleus and the motor nuclei of the cranial
      nerves. Additionally, spinal cord motoneurons appeared positive to both markers.
      Substantial differences in the ChAT and AChE distribution between zebrafish and
      other fish species were observed, which could be important because zebrafish is
      widely used as a genetic or developmental animal model.

PMID- 15156581
TI  - Induction of enhanced green fluorescent protein expression in response to lesions
      in the nervous system.
AB  - We have generated a mouse strain carrying a transgene driven by a strong and
      ubiquitous promoter (human cytomegalovirus hCMV/beta-actin) and containing an
      enhanced green fluorescent protein (eGFP) coding sequence upstream of the 3'
      untranslated region (3'UTR) of tissue-type plasminogen activator (t-PA) mRNA. The
      3'UTR of t-PA mRNA is known to be involved in the reversible deadenylation and
      translational repression of transcripts in mouse oocytes. hCMV/beta-actin-eGFP
      3'UTR t-PA transgenic mice express eGFP mRNA in all brain structures analyzed but
      lack eGFP fluorescence, with the exception of blood vessels, choroid plexus, and
      Purkinje cells. Taking advantage of these features, we tested whether certain
      pathological conditions, in particular injuries of the nervous system, might
      trigger eGFP fluorescence in traumatized cells or neurons. From this perspective,
      we analyzed eGFP mRNA expression and eGFP fluorescence in experimental models of
      nervous system lesions, such as motoneuron axotomy and cerebral stroke induced by
      middle cerebral artery occlusion. We found an increase in eGFP fluorescence in
      specific brain areas in cells suffering or reacting to these injuries. This
      increased fluorescence is correlated with an increased transcription of eGFP in
      lesioned cells, presumably enhanced by a release of the translational silencing
      mediated by the 3'UTR region of the t-PA mRNA. This transgenic mouse model may
      prove useful to study the development of neurodegenerative lesions.

PMID- 15156582
TI  - Distribution of glutamatergic immunoreactive neurons in the terminal abdominal
      ganglion of the crayfish.
AB  - Using an antiserum directed against glutamate, we have analyzed the distribution
      of glutamate-like immunoreactive neurons in the terminal abdominal ganglion of
      the crayfish Procambarus clarkii. Approximately 160 central neurons (157 +/- 8;
      mean +/- SEM, n = 8) showed positive glutamate-like immunoreactivity, which
      represents approximately 25% of the total number of neurons in the terminal
      ganglion. Using a combination of intracellular staining with the marker Lucifer
      yellow and immunocytochemical staining has shown that most excitatory motor
      neurons are glutamatergic and that glutamate acts as an excitatory transmitter at
      peripheral neuromuscular junctions. Seven of 10 identified spiking local
      interneurons and only 2 of 19 identified ascending interneurons, showed positive
      immunoreactivity. Our observation that inhibitory spiking interneurons were
      immunopositive, whereas excitatory ascending interneurons were immunonegative,
      indicates that glutamate is likely to act as an inhibitory neurotransmitter
      within the central nervous system. Local pressure injection of L-glutamate into
      the neuropil of the ganglion caused a hyperpolarization of the membrane
      potentials of many interneurons. gamma-Aminobutyric acid (GABA)ergic
      posterolateral nonspiking interneurons and the bilateral nonspiking interneuron
      LDS showed no glutamate-like immunoreactivity, whereas non-GABAergic
      anterolateral III nonspiking interneurons showed glutamate-like immunoreactivity.
      Thus, not only GABA but also glutamate are used in parallel as inhibitory
      neurotransmitters at central synapses.

PMID- 15156584
TI  - Type 1 nitrergic (ND1) cells of the rabbit retina: comparison with other axon
      bearing amacrine cells.
AB  - NADPH diaphorase (NADPHd) histochemistry labels two types of nitrergic amacrine
      cells in the rabbit retina. Both the large ND1 cells and the small ND2 cells
      stratify in the middle of the inner plexiform layer, and their overlapping
      processes produce a dense plexus, which makes it difficult to trace the
      morphology of single cells. The complete morphology of the ND1 amacrine cells has
      been revealed by injecting Neurobiotin into large round somata in the inner
      nuclear layer, which resulted in the labelling of amacrine cells whose proximal
      morphology and stratification matched those of the ND1 cells stained by NADPHd
      histochemistry. The Neurobiotin-injected ND1 cells showed strong homologous
      tracer coupling to surrounding ND1 cells, and double-labelling experiments
      confirmed that these coupled cells showed NADPHd reactivity. The ND1 amacrine
      cells branch in stratum 3 of the inner plexiform layer, where they produce a
      sparsely branched dendritic tree of 400-600 microm diameter in ventral peripheral
      retina. In addition, each cell gives rise to several fine beaded processes, which
      arise either from a side branch of the dendritic tree or from the tapering of a
      distal dendrite. These axon-like processes branch successively within the
      vicinity of the dendritic field before extending, with little or no further
      branching, for 3-5 mm from the soma in ventral peripheral retina. Consequently,
      these cells may span one-third of the visual field of each eye, and their spatial
      extent appears to be greater than that of most other types of axon-bearing
      amacrine cells injected with Neurobiotin in this study. The morphology and tracer
      coupling pattern of the ND1 cells are compared with those of confirmed type 1
      catecholaminergic cells, a presumptive type 2 catecholaminergic cell, the type 1
      polyaxonal cells, the long-range amacrine cells, a novel type of axon-bearing
      cell that also branches in stratum 3, and a type of displaced amacrine cell that
      may correspond to the type 2 polyaxonal cell.

PMID- 15156583
TI  - Caspase-3 and caspase-9 mediate developmental apoptosis in the mouse olfactory
      system.
AB  - Neuronal apoptosis is a key component in the sculpting of tissues during
      embryonic and postnatal development and is driven largely by the action of
      caspases. In the mouse olfactory system, caspase-3 and -9 are expressed in
      olfactory receptor neurons (ORNs) of adult mice, and their selective retrograde
      activation drives ORN apoptosis following ablation of their target, the olfactory
      bulb (OB). Here, we show that both of these caspases are expressed at the
      earliest stages of ORN embryonic development, and their expression is
      concentrated in outgrowing ORN axons. The retention, in null mice for both
      caspases, of a population of ORNs that would normally undergo developmental
      apoptosis beginning at E13 of development, results in a permanently expanded
      population of ORNs. In turn, in some caspase-3 null mice, the ORN target organ,
      the OB, also develops abnormally, resulting in the formation of secondary,
      apparently functional, extracranial ectopic OBs.

PMID- 15156585
TI  - Dynamic soft elasticity in monodomain nematic elastomers.
AB  - We study the linear dynamic-mechanical response of monodomain nematic liquid
      crystalline elastomers under shear in the geometry that allows the director
      rotation. The aspects of time-temperature superposition are discussed at some
      length and Master Curves are obtained between the glassy state and the nematic
      transition temperature Tni. However, the time-temperature superposition did not
      work through the clearing point Tni, due to the transition from the "soft
      elasticity" nematic regime to the ordinary isotropic rubber response. We focus on
      the low-frequency region of the Master Curves and establish the power law
      dependence of the modulus G' alpha w(a). This law agrees very well with the
      results of the static stress relaxation, where each relaxation curve obeys the
      analogous power law G' alpha t(-a) in the corresponding region of long times and
      temperatures.

PMID- 15156586
TI  - US disburses first round of AIDS funds.

PMID- 15156587
TI  - Sex determination, differentiation, and identity.

PMID- 15156588
TI  - Sex determination, differentiation, and identity.

PMID- 15156589
TI  - Sex determination, differentiation, and identity.

PMID- 15156590
TI  - Vasopressin versus epinephrine for cardiopulmonary resuscitation.

PMID- 15156591
TI  - Vasopressin versus epinephrine for cardiopulmonary resuscitation.

PMID- 15156592
TI  - Vasopressin versus epinephrine for cardiopulmonary resuscitation.

PMID- 15156593
TI  - Folic acid and the prevention of neural-tube defects.

PMID- 15156594
TI  - Folic acid and the prevention of neural-tube defects.

PMID- 15156595
TI  - Hepatitis A vaccine.

PMID- 15156596
TI  - Case 5-2004: a man with slurred speech and left hemiparesis.

PMID- 15156597
TI  - A new in vitro blood load test using a magnesium stable isotope for assessment of
      magnesium status.

PMID- 15156598
TI  - Biography as history.

PMID- 15156599
TI  - Attachment inhibitor shows promise.

PMID- 15156600
TI  - Marijuana effective for polyneuropathy.

PMID- 15156601
TI  - First AIDS vaccine trial in Germany.

PMID- 15156602
TI  - Treatment of Wilson's disease.
AB  - On the basis of literature review and own experience we presented the method of
      treatment of Wilson's disease. Causative treatment has been impossible so far,
      although gene therapy could be real in the future. Nowadays the principle of
      treatment is the elimination of the excess of easily mobilized copper by
      chelating agents or blocking the intestinal absorption of copper. Chelation
      therapy, aimed at mobilizing copper from the affected organs and promoting its
      excretion in the urine or stool is the most important. The major chelating agent
      is d-penicillamine, which is quite effective but not without some side effects.
      Alternative chelating agents such as trientine and tetrathiomolybdate have also
      been successfully employed. Zinc salts are also of therapeutic value. They
      promote copper excretion by inducing the synthesis of metallothionein in the
      intestine, thereby blocking copper absorption from the gut. Zinc salts have
      almost no side effects. They cannot be used as an initial treatment, but are very
      effective for maintenance therapy. The chelation therapy is ineffective in
      patients with acute liver failure with encephalopathy and hemolysis. In these
      cases, liver transplantation is the only hope for survival. Liver
      transplantations in patients with dominating psychoneurological symptoms are open
      to discussion.

PMID- 15156603
TI  - Results of treatment of Wilson's disease--own observations.
AB  - BACKGROUND: Causative treatment of genetically determined Wilson's disease (WD)
      has been impossible so far, although gene therapy could be real in the future.
      Nowadays the principle of treatment is the elimination of the excess of easily
      mobilized copper, bound by chelating agents, the most important of which is d
      penicillamine, through the kidneys. Blocking of the intestinal absorption of
      copper by administration of zinc preparations, which additionally induce hepatic
      metallothionein synthesis, is also possible. The aim of our study was to present
      own observations and results of treatment of Wilson's disease. MATERIAL/METHODS:
      During the last 16 years, we have observed 33 patients aged 13-60 (mean age 27
      years) with various forms of WD. The studied group consisted of 11 females and 21
      males, admitted to hospital or seen at the Specialistic Outpatient Department of
      Hepatology with various diagnoses. In addition to standard laboratory tests, the
      levels of ceruloplasmin, serum and urine copper, as well as the activity of some
      hepatic enzymes, proteins and HBV/HCV infection markers were determined. The
      patients were also examined by a neurologist and an ophthalmologist, with
      psychiatric consultation if necessary. Taking into account the overall clinical
      presentation, the patients were divided into the following groups according to
      the form of the disease: fulminant, acute, hepatic, hepatic with neurological and
      psychiatric symptoms, neuropsychiatric, asymptomatic. RESULTS: All the patients
      were initially treated with d-penicillamine. In most of them, no side effects
      were observed. The treatment was continued according to the levels of copper
      excreted with urine (for 10 years at the longest). After obtaining clinical
      improvement with reduced amount of copper excreted with 24-h urine, we tapered d
      penicillamine doses or even discontinued the drug, introducing zinc preparations.
      In asymptomatic carriers, zinc preparations were used throughout the period of
      treatment. CONCLUSIONS: Early institution of chelation treatment is associated
      with good prognosis both in hepatic and neurological forms of WD. Zinc
      preparations are effective and safe in neurological and oligosymptomatic forms of
      the disease.

PMID- 15156604
TI  - Serum selenium levels in alcoholic liver disease.
AB  - BACKGROUND: The pathomechanism of liver damage in chronic alcoholic liver disease
      has not been fully elucidated yet. It seems undoubted that one of the mechanisms
      of alcohol-induced liver damage involves free radical reactions leading to
      peroxidation of proteins and lipids. The most important defense mechanisms are
      associated with the activity of antioxidative enzymes, among which glutathione
      peroxidase (GSH-Px), belonging to so-called 'free radical scavengers' should be
      mentioned. Selenium, regarded as a bioelement, is present in GSH-Px. Involved in
      numerous redox reactions, it belongs to the factors protecting the organism from
      oxidative shock. The aim of the study was to determine the selenium levels in
      blood serum of chronic alcohol abusers and to find potential correlations with
      the parameters of liver damage. MATERIAL/METHODS: The study was carried out in a
      group of 25 subjects (21 males, 4 females), treated in the Clinic or Outpatient
      Department of Hepatology for chronic alcoholic liver disease. At the time of the
      study, the patients had abstained from drinking for a period from one month to a
      year. Selenium was determined with atomic absorption spectroscopy method, using
      the hydride generation technique. The control group consisted of 11 males and 7
      females. RESULTS: Statistical analyses of the control group indicated a
      significantly higher blood serum selenium level in males than in females. The
      patients demonstrated elevated aminotransferase activity, normal Falk, markedly
      increased GGTP. Mean INR was 1.4 and albumin concentration 3.3 g/l. Blood serum
      selenium levels in male patients were significantly lower in comparison with
      normal values. The analysis of correlations between some liver function
      parameters and selenium levels demonstrated a positive correlation between the
      levels of albumin and selenium. Serum selenium level was inversely proportional
      to ALAT activity. No correlations between selenium levels and INR levels, or GGTP
      activity were found. CONCLUSIONS: 1. Serum selenium levels differ in male and
      female populations. In healthy men, the level of Se in the serum is higher. 2.
      Antioxidative activity measured by serum Se level is low in men with chronic
      alcoholic liver disease (during the abstinence period). 3. Increased selenium
      level in the hair may indicate the presence of certain antioxidative reserve,
      which requires further studies.

PMID- 15156605
TI  - Acute hepatic failure in the course of alcohol-paracetamol syndrome--case report.
AB  - Acetaminophen belongs to the antipyretic and analgesic drugs most commonly used
      all over the world. In western Europe, primarily in Great Britain, as well as in
      the US, increasing incidence of acute liver failure due to the overdose of the
      drug has been reported. The report presents a description of alcohol-paracetamol
      syndrome, which led to the development of acute hepatic failure with numerous
      complications. Intensive symptomatic and causal treatment with N-acetylcysteine
      resulted in complete recovery.

PMID- 15156607
TI  - Progress of liver disease in chronic hepatitis C patients who failed antiviral
      therapy.
AB  - BACKGROUND: The natural history of chronic hepatitis C (CHC) is characterized by
      gradual progression of hepatic fibrosis, which can lead to cirrhosis. The aim of
      our study is to examine the influence of ineffective antiviral therapy on
      progress of the liver disease in CHC patients. MATERIAL/METHODS: Seventy-seven
      treated and non-treated CHC patients with two liver biopsies: baseline (BLB) and
      control (CLB) performed at least 12 months after treatment and at least 18 months
      from BLB in non-treated patients were studied. Twenty-eight CHC patients (age:
      40.3 +/- 9.2 yrs; 22M), non-responding to interferon therapy (all with
      pretreatment fibrosis), were compared with non-treated patients divided into
      subgroups NT1 (21 patients [age: 45.1 +/- 11.2 yrs; 10M] with fibrosis in BLB)
      and NT2 (28 patients [age: 34.7 +/- 12.6; 17M] without fibrosis in BLB). The
      baseline clinical data between study groups as well as activity grade and
      fibrosis staging scores of the paired biopsy samples were compared. RESULTS: All
      three groups were comparable in terms of mean duration of the disease and
      interval between biopsies. There were no significant differences of clinical
      features in T and NT1 groups. In CLB, the patients from NT1 group presented non
      significant worsening of staging and grading and in NT2 group a slight but
      statistically significant increase in grading was observed. In contrast, the
      treated patients had a slight, but significant improvement in liver histology.
      CONCLUSIONS: Antiviral treatment stopped the progression of liver disease in CHC
      despite the lack of biochemical and virological response. In non-treated patients
      a slight tendency to worsening of morphological parameters was observed.

PMID- 15156606
TI  - Treatment of acute hepatitis C.
AB  - BACKGROUND: We presented the results of treatment in patients with AHC and
      compared these findings with natural outcome of AHC in untreated patients.
      MATERIAL/METHODS: Ten treated AHC patients (5F/5M, mean age: 35.5 yrs; all HCV
      RNA-positive including 9 anti-HCV-positive). Antiviral treatment was started
      within 3 to 18 (median 9) weeks after the onset of acute hepatitis including
      eight patients with monotherapy of IFN and two patients with combined (IFN +
      ribavirin) therapy. CONTROL GROUP: Fifty consecutive untreated AHC patients
      (26F/24M, mean age: 40.8 yrs; all HCV-RNA-positive, including 29 anti-HCV
      positive) without contraindications to treatment with IFN. RESULTS: Only one
      treated patient presented no response and the other 9 patients presented rapid
      normalization of serum ALT levels in 4th-6th week of the therapy. In two
      patients, ALT increased in the course of therapy and after adding ribavirin the
      treatment was continued up to 48 weeks in total. At the end of treatment point,
      nine patients showed biochemical and virological response, but one relapsed both
      in biochemical and virological respect and virological relapse was observed in
      another one. Finally, sustained response was observed in 7 of 10 (70%) of treated
      compared with 22 of 50 (44%) untreated patients (p = n.s.). The beneficial effect
      of antiviral treatment was observed among patients with early anti-HCV
      seroconversion: 7 of 9 treated patients recovered persistently compared with 8 of
      29 untreated (p = 0.021). CONCLUSIONS: The antiviral therapy in AHC seems to be
      effective and should be widely used, especially for individuals with early anti
      HCV seroconversion. Ribavirin seems to be helpful for patients, who have not
      responded to interferon monotherapy.

PMID- 15156608
TI  - Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis-
      a case report and review of literature.
AB  - Adult giant cell hepatitis (AGCH) is a rare event and only about 100 cases have
      been reported within the last 20 years. The AGCH has been observed in association
      with viral infection, drug reactions or autoimmune disorders but in many cases
      its etiology remains unclear. AGCH manifests clinically as severe form of
      hepatitis histologically characterized by diffuse giant cell transformation of
      hepatocytes. We report the case of a 39-yr-old man with acute community-acquired
      hepatitis without previous pathology of the liver. Laboratory data revealed
      slight hypergammaglobulinemia and high titer of anti-smooth-muscle antibody with
      negative serology of hepatotropic viruses and absence of other known causes of
      hepatitis. Preliminary diagnosis of autoimmune hepatitis was established,
      additionally confirmed by excellent clinical and biochemical improvement during
      corticosteroid treatment. A liver biopsy showed the typical findings of
      panlobular syncytial giant cell hepatitis and positive HCV-RNA both in serum and
      liver. The above verified the diagnosis of acute type C hepatitis manifested
      histologically as adult giant cell hepatitis. After three months of treatment we
      withdrew corticosteroids as spontaneous clearance of HCV occurred and the lack of
      autoantibodies in serum as well as significant improvement of liver histology was
      ascertained. Within 30 months of the follow-up we have not observed biochemical
      and immunological abnormalities and control liver biopsy has shown no signs of
      hepatitis.

PMID- 15156609
TI  - Assessment of selected clinical factors as predictors of response to combined
      interferon-alpha plus ribavirin therapy among patients with chronic hepatitis C.
AB  - BACKGROUND: Combined interferon-alpha (IFN) plus ribavirin therapy is recommended
      as first-line regimen treatment of chronic hepatitis C (CHC) patients. The aim of
      the study was to evaluate the selected clinical factors in the prediction of
      response to IFN with ribavirin for initial therapy and retreatment of CHC.
      PATIENTS AND METHODS: Ninety eight consecutive CHC patients who completed the
      combined IFN with ribavirin therapy (24 or 48 weeks), including 79 naive patients
      (age: 41.0 +/- 10.9 yrs; 51M; NAIVE group) and 19 nonsustained responders to
      prior IFN monotherapy (age: 40.8 +/- 10.2 yrs; 10M; RETHERAPY group). Sustained
      Response (SR) was defined as persistent normalization of ALT and loss of serum
      HCV-RNA 6 months after the end of treatment; all other patients were defined as
      nonresponders (NR). Age, gender, pretreatment histology (assessed according to
      Ishak's scoring system) and baseline ALT, gamma-GTP and iron serum levels were
      compared in SR and NR patients, separately in NAIVE and RETHERAPY groups.
      RESULTS: The baseline clinical characteristics of NAIVE and RETHERAPY group did
      not differ significantly. 28 of 79 (35.4%) NAIVE patients and 9 of 19 (47.4%) RE
      THERAPY patients achieved SR to the therapy. NAIVE sustained responders presented
      significantly lower staging scores and gamma-GTP levels in comparison with
      nonresponders. Multivariate logistic regression analysis showed that only
      fibrotic score lower than 3 was independently (p = 0.04) associated with SR. In
      RETHERAPY group, only female gender was positively correlated with SR. The other
      analyzed parameters did not significantly differ between responders and
      nonresponders. CONCLUSIONS: The results of the present study suggest that
      sustained response to combined therapy in naive CHC patients is associated with
      absence or minimal hepatic fibrosis prior to the therapy. Among retherapy
      patients, females are more likely to achieve sustained response, irrespective of
      fibrosis stage.

PMID- 15156610
TI  - Presence of HCV RNA in hepatic tissue and effectiveness of treatment with
      interferon and ribavirin.
AB  - BACKGROUND: The aim of the study was to assess the prognostic value of HCV RNA
      detection in hepatic tissue for the response to treatment with interferon alfa
      (IFN) and ribavirin (RIB) in patients with chronic hepatitis C. PATIENTS AND
      METHODS: A group of 55 patients infected with HCV was examined before the
      commencement of treatment with IFN and RIB. In all of them HCV RNA was detected
      in the serum. The presence of HCV RNA in hepatic tissue was confirmed using a
      technique combining a new method of HCV RNA extraction from hepatic tissue and
      detection of HCV RNA with RT-PCR Cobas Amplicor Roche tests. The group of 55
      patients received IFN (3-6 MU, 3 times a week) and RIB (800-1200 mg daily) for 6
      to 12 months. The response to treatment was assessed 6 months after completion of
      the therapy. Sustained response (SR) was defined as absence of HCV RNA in the
      serum and normalization of ALT levels. RESULTS: The presence of HCV RNA in
      hepatic tissue was confirmed in 48 patients (group A), and in 7 (group B) HCV RNA
      was not detected in the liver. SR was observed in 17 patients from group A and 6
      from group B. Significant correlation (p < 0.05) was found between detection of
      HCV RNA in hepatic tissue and response to IFN + RIB therapy. CONCLUSIONS: As it
      follows from our results, the detection of HCV RNA in the hepatic tissue of a
      patient with chronic hepatitis C may be a negative prognostic factor for the
      patient's response to IFN + RIB therapy.

PMID- 15156611
TI  - Hepatitis C virus RNA level changes in sera during different regimens of
      treatment in patients with chronic hepatitis C.
AB  - BACKGROUND: Interferon alfa-2b (IFN) has been shown to be effective for chronic
      hepatitis C infection, but treatment efficacy is still limited. Sustained
      response after interferon alfa monotherapy is achieved in about 15-25%. Great
      efforts are made to identify more effective forms of therapy. Some of them
      include modifications of dosage of antiviral drugs, duration of the therapy and
      more optimal selection of patients for the treatment. Several virus- and host
      related predictive factors for response to antiviral treatment have been
      proposed. One of the key predictive factors of sustained response to therapy are
      the pretreatment levels of viremia as well as the dynamics of initial changes of
      HCV-RNA levels assessed during antiviral therapy. AIM: The aim of our study was
      to compare changes of HCV-RNA viremia in patients with chronic hepatitis C during
      different regimens of antiviral treatment. MATERIAL/METHODS: 21 patients
      chronically infected with HCV (anti-HCV positive, HCV-RNA positive by PCR) were
      enrolled in the study. 11 patients (Group I) were treated with interferon alfa-2b
      (IFN-alpha 2b) at 3 MU tiw doses administered subcutaneously for 12 months. 10
      patients (Group II) received 3 MU of IFN-alpha 2b daily during the first month
      and later the treatment was continued with the same dosage tiw for the next 11
      months. The response to the treatment was assessed according to the generally
      accepted criteria after 6-month follow-up. The initial decline of HCV-RNA after 4
      weeks of therapy was assessed. RESULTS: Results are presented in the Table. HCV
      RNA expressed in copy/ml. CONCLUSION: The initial decline of HCV-RNA level during
      the first 4 weeks of antiviral therapy with interferon correlates with the final
      response to the treatment. The greater decline of viremia was observed in the
      group of patients treated with the 'induction' variant of treatment.

PMID- 15156612
TI  - Blood serum glutathione alpha s-transferase (alpha GST) activity during antiviral
      therapy in patients with chronic hepatitis C.
AB  - BACKGROUND: Glutathione transferases (GST) belong to enzymes involved primarily
      in the processes of detoxification of exo- and endogenous substances.
      Immunohistochemical studies have demonstrated that alpha-GST present in the liver
      is localized exclusively in hepatocytes. The activity of alpha-GST is reported to
      reflect interstitial liver damage better than that of aminotransferases,
      especially in patients with autoimmune hepatitis, and, according to some authors,
      also in patients with chronic hepatitis C. The GST system has also been proposed
      to be indirectly involved in hepatocellular damage due to hepatitis C virus (HCV)
      infection. THE AIM OF THE STUDY: Was to assess the utility of alpha-GST as an
      accessory marker in monitoring antiviral therapy in patients with chronic
      hepatitis C. MATERIAL/METHODS: 21 patients (12 males and 9 females) with chronic
      HCV infections were evaluated. The diagnosis was based on clinical presentation
      and detection of anti-HCV, as well as the presence of HCV-RNA in blood serum
      detected by PCR. Fifteen patients (group I) were treated with interferon alpha-2b
      (IFN alpha-2b) at 3 MU s.c. doses administered three times a week (tiw) and
      ribavirin at 0.8 do 1.2 g/day doses, whereas 6 remaining patients (Group II) were
      treated with IFN alpha-2b alone at 5 MU s.c. tiw doses. The activity of alpha GST
      was determined with ELISA before and after 6 months of treatment, together with
      assessment of HCV-RNA viremia determining the decision concerning continuation of
      the therapy. RESULTS: The results are presented in Table 1 as mean values +/- SD.
      *p, 0.05. CONCLUSIONS: Combined antiviral treatment with IFN alpha-2b and
      ribavirin, and IFN alpha-2b monotherapy reduce blood serum alpha-GST activity in
      patients with chronic hepatitis C. alpha-GST is less useful as a liver damage
      parameter than ALT in monitoring of antiviral treatment.

PMID- 15156613
TI  - Autoimmune hepatitis in the material of Department and Regional Hospital of
      Infectious Diseases in Gdansk.
AB  - BACKGROUND: The aim of the study was the analysis of patients with autoimmune
      hepatitis (AIH), with respect to diagnostics, clinical course and treatment,
      based on the material from the wards of infectious diseases. MATERIAL/METHODS:
      The study was carried out in the group of 106 AIH patients--95 females aged 11-81
      (mean age 46 years) and 11 males aged 8-73 (mean age 35 years). The diagnosis of
      AIH was based on international criteria, including biochemical test results,
      autoantibodies, and liver tissue morphology. Serological test excluded hepatitis
      of viral etiology. Diagnostic procedures included also blood cell count,
      biochemical parameters of liver function with protein fractions, immunoassays
      (immunoglobulins, autoantibodies), according to commonly used methods. Liver
      biopsies were performed in 93 patients. RESULTS: The clinical presentation
      mimicked acute viral hepatitis in 75% of cases, in the remaining 25% corresponded
      to chronic viral hepatitis. 26% had other coincident disorders of autoimmune
      etiology. In 84% the initial stage of the disease was characterized with
      moderately severe course, in 11%--severe, 7% of the patients died--half of them
      at the initial stage of the disease. The following morphological patterns of
      hepatic abnormalities were observed: hepatitis chronica agresiva, fibrosis
      periportalis, hepatitis chronica agresiva in cirrhosim vertens, cirrhosis hepatis
      activa, hepatitis chronica persistence, hepatitis granulomatosa. Over 40% of
      patients demonstrated relapses of the disease due to discontinuation of treatment
      after obtaining clinical and biochemical remission. 51 patients were treated with
      glucocorticosteroid monotherapy, the same number with glucocorticosteroids
      combined with azathioprine, 1 female patient underwent liver transplantation. In
      nearly 30% of patients, the diagnosis of AIH was established after a period of
      persistence of pathologic symptoms of over a year. CONCLUSIONS: Late diagnoses of
      AIH indicate insufficient knowledge of the disease among physicians. The methods
      of treatment used in AIH are not sufficiently effective. Discontinuation of
      treatment should be preceded in each case by overall assessment of the pathologic
      process, including biochemical parameters, autoantibody level and liver
      histopathology.

PMID- 15156614
TI  - Assessment of gastric secretory function by 24-hour pH-metry in patients with
      hepatic cirrhosis due to HBV infection, before and after non-shunt type Sugiura
      procedure.
AB  - BACKGROUND: Assessment of gastric secretory function by 24-hour pH-metry in
      patients with hepatic cirrhosis due to HBV infection, before and after non-shunt
      type Sugiura procedure. AIM OF THE STUDY: Advanced chronic hepatopathies are very
      often accompanied by pathologic changes in the stomach as well as functional
      disturbances affecting the upper gastrointestinal tract. They include ulceration,
      erosions, and congestive (portal) gastropathy, reported with increasing
      frequency. Some of these patients undergo surgical treatment to prevent recurrent
      esophageal variceal bleeding. Because of considerable differences in gastric
      hydrochloric acid secretion, its assessment was attempted in patients with
      hepatic cirrhosis and portal hypertension before (group II) and after (group III)
      non-shunt type surgical procedure. MATERIAL/METHODS: The study was carried out in
      two groups of patients, consisting of 11 patients each, and a control group of 15
      healthy volunteers. Subjects over 65 years of age, with concurrent chronic
      conditions, history of surgical procedures (except for Sugiura procedure) and
      treated with drugs affecting gastric secretion were excluded from the study. All
      the subjects qualified for the study underwent pH-metry with a DL70 pH-meter
      equipped with a glass electrode. Median pH (Me) and mean pH values (arithmetic
      mean, AM) from 24 h were used in analysis. RESULTS: The following results were
      obtained--in the control group Me 1.57, AM. 1.97; in group II Me 2.04, AM 2.53.
      In the group of patients after Sugiura procedure Me was 2.83 and AM 3.12. No
      statistically significant differences in gastric secretion were found between the
      studied groups in statistical analysis using Cochran, Cox and Student-t tests.
      CONCLUSION: There are no statistically significant differences in gastric
      secretion determined by 24-hour pH-metry in patients with hepatic cirrhosis due
      to HBV infection and portal hypertension before and after non-shunt type Sugiura
      procedure.

PMID- 15156615
TI  - Assessment of correlation between histopathologic changes of gastric mucosa
      according to Whitehead's classification and extent of liver damage according to
      Knodell's scale in patients with chronic hepatopathy.
AB  - AIM OF THE STUDY: Patients with chronic liver damage often suffer from functional
      disturbances and pathologic changes in the stomach, including ulceration,
      erosions and chronic gastritis. It was attempted to establish whether there is a
      correlation between histopathologic abnormalities of the gastric mucosa and the
      extent of histopathologic changes in liver bioptates, i.e. inflammatory activity
      and fibrosis (Knodell's index) in patients with chronic hepatopathy.
      MATERIAL/METHODS: The study was carried out in 4 groups of patients: groups I--10
      subjects with autoimmune hepatitis, group II--9 patients with chronic toxic liver
      damage, group III--11 patients with chronic hepatitis caused by HBV, and group IV
      -36 patients with chronic hepatitis caused by HCV. All the patients underwent
      gastroscopy with collection of gastric mucosa bioptates (from the antrum and the
      gastric body) as well as liver biopsy. RESULTS: The most frequent gastroscopy
      finding in all the studied groups were signs of gastritis: in group I--90%, in
      group II--78%, in group III--64% and in group IV--99%. Gastric mucosa
      histopathology assessed according to Whitehead's classification most frequently
      led to the diagnosis of gastritis chronica profunda (Group I--80%, Group II--78%,
      Group III--73% and Group IV--58%). No correlation was found between inflammatory
      activity in the liver assessed according to Knodell's scale and the extent of
      changes in histopathology of the gastric mucosa (p = 0.1). A negative correlation
      which, however, does not reach significance level (p = 0.054), is observed
      between the extent of fibrosis in liver bioptates and histopathologic
      abnormalities in the gastric mucous membrane. CONCLUSION: No statistically
      significant correlation between the extent of gastric mucosa damage and severity
      of inflammatory lesions and hepatic fibrosis was found.

PMID- 15156617
TI  - Preliminary assessment of utility of radiofrequency ablation technique in
      treatment of primary hepatocellular carcinoma (HCC) in patients with hepatic
      cirrhosis.
AB  - BACKGROUND: Primary hepatocellular carcinoma very often develops in the cirrhotic
      liver. Surgical treatment of cirrhotic patients is associated with considerable
      risk. Even partial resection of the liver carries the risk of liver failure in
      such patients. Therefore, the thermoablation technique used in patients with
      liver tumors and cirrhosis, arouses considerable interest. The aim of the study
      was preliminary assessment of the value of radiofrequency (RFA) ablation in the
      treatment of HCC in patients with hepatic cirrhosis. MATERIAL/METHODS: From April
      2001 to April 2002, 14 patients aged 30-79 with cirrhosis and focal lesions of
      primary liver tumor type (carcinoma hepatocellulare) were treated with
      transcutaneous thermoablation. Transcutaneous thermoablation with Cool Tip
      Equipment probe (Radionics) was performed under local anesthesia induced after
      intravenous sedation, or under general anesthesia with propofol (TIVA). In case
      of single lesions up to 3 cm in diameter, the exposure to thermal waves lasted 12
      min, in case of larger lesions 2 to 4 sessions were used. The effects of RFA were
      assessed intraoperatively by means of USG, measuring the coagulation area, and
      then MRI was performed to confirm complete destruction of the lesions. The
      response to treatment was assessed by CT after 8 weeks. RESULTS: Among 8 patients
      with single focal lesions complete remission (CR) was obtained in 4, and partial
      remission (PR) in the remaining 4 cases. One subject with CR died 5 months later
      because of hemorrhage from esophageal varices. Among 6 patients with more than
      one HCC focus subjected to RFA, CR was obtained in 1, PR in 3, and one female
      patient who underwent the procedure in the period of non-compensated liver
      function, died 1.5 months later because of hepatic failure. Repeated
      thermoablation is considered in patients with PR. CONCLUSIONS: 1. Radiofrequency
      ablation is a safe method of treatment of HCC in patients with cirrhosis. 2. One
      of the advantages of RFA is that it can be performed repeatedly. 3. RFA can be
      combined with other methods.

PMID- 15156616
TI  - Disturbances of iron metabolism in chronic liver diseases.
AB  - BACKGROUND: Systematic biochemical and histopathological studies carried out in
      patients with diagnosed chronic liver diseases (cirrhosis, hepatocellular
      carcinoma) confirm the important pathogenetic role of commonly occurring
      accumulation of iron deposits, and not only in the classic form of
      hemochromatosis. The reports concern the pathologic role of iron storage in the
      liver often accompanying metabolic disturbance syndrome including obesity, type
      II diabetes and hypertension. The aim of the study was preliminary assessment of
      the incidence of iron metabolism disturbances in the population of patients with
      chronic liver diseases. MATERIAL/METHODS: Among 351 patients of the Department of
      Infectious Diseases who had histopathologic investigations of liver bioptates
      performed in 2000-2001, 99 subjects (28%) with morphological confirmation of iron
      deposition in the liver were selected. Retrospective analysis based on data from
      the patients' medical records took into consideration demographic information,
      results of laboratory tests (blood levels of hemoglobin, ALAT, iron, ferritin)
      and the ultimate diagnosis. The correlations between iron metabolism disturbances
      and the observed liver pathology were analyzed. RESULTS: The study group
      consisted of 99 subjects including 77 males (mean age 42.8 yrs) and 22 females
      (mean age 47.5 yrs). Most of them had been diagnosed with chronic hepatitis C, (N
      = 39). Liver damage due to hyperlipidemia was diagnosed in 12, and toxic liver
      damage in 11 patients. Subjects with chronic renal failure and after antitumor
      therapy accounted for 14%. In 7 patients, hemochromatosis was diagnosed or
      suspected. In that group, mean serum ferritin level amounted to 959.3 ng/ml. In
      79% of cases, ALT values fell within the 41-500 IU/l range, whereas iron and
      ferritin levels exceeded the normal limits in 49% and 71% of cases, respectively.
      The preliminary analysis of pathologic iron accumulation in liver bioptates in
      relation to biochemical parameters of iron metabolism measured in the blood did
      not allow unequivocal confirmation of linear correlation between these phenomena.
      CONCLUSIONS: 1. Over 1/4 of patients diagnosed because of chronic liver diseases
      demonstrated excessive accumulation of iron in liver bioptates. 2. The analyzed
      group consisted predominantly of males with chronic hepatitis C. 3. Metabolic or
      toxic liver damage was diagnosed n 1/3 of cases. 4. No unequivocal confirmation
      of correlation between pathologic iron accumulation in the liver and values of
      iron metabolism parameters in blood was obtained.

PMID- 15156618
TI  - Implications of practicing informatics in the public health sector.

PMID- 15156619
TI  - Disseminating public health practice guidelines in electronic medical record
      systems.
AB  - An evaluation of public health practice guidelines published by CDC was conducted
      to determine the feasibility of disseminating them through electronic medical
      record (EMR) systems. Of 1,069 guidelines evaluated, 360 contained at least one
      recommendation that could be presented as an alert or reminder to the clinician
      during the patient encounter. These guidelines were in the areas of: HIV (59),
      sexually transmitted diseases (8), health care associated infections (14),
      tuberculosis (TB) (25), immunizations/vaccine-preventable diseases (80), other
      infectious diseases (134), reproductive health diseases (8), cancers (9),
      diabetes (5), and other chronic diseases (18). Further efforts to disseminate CDC
      guidelines through EMR systems are in progress.

PMID- 15156621
TI  - Electronic medical billing records and public health surveillance: comparison of
      two systems used during the 1996 Atlanta Olympic Games.
AB  - For selected diagnoses of public health interest during the 1996 Olympic Games,
      the authors compared data concurrently obtained on the same patient population by
      two separate surveillance systems: (1) an existing hospital electronic medical
      billing records system and (2) a system based on manual record abstraction.
      Counts of total patient visits closely agreed, though the two systems differed
      considerably in some diagnostic categories, especially injuries. The authors
      concluded that while causation, risk factors, and illness severity are not
      reflected directly in standard International Classification of Diseases (ICD)
      codes, and "E" codes to indicate causation may not be used, special-purpose
      surveillance systems based on existing computerized medical records may be as
      effective as manual data abstracting.

PMID- 15156620
TI  - Public health, data standards, and vocabulary: crucial infrastructure for
      reliable public health surveillance.
AB  - The present, rapid adoption of electronic records in clinical care is likely to
      shift public health surveillance from passive, human-mediated abstraction to
      active, computer-generated reports. However, the accuracy and efficiency of this
      process depends upon the adoption of consistent information standards from beside
      to population and the relevance of these data to public health. This article
      outlines the current status of data standards of relevance to public health and
      expands upon the ideal goal state in which health information would be collected
      once and then reused for multiple health-related purposes, including public
      health surveillance.

PMID- 15156622
TI  - EpiQMS: an Internet application for access to public health data for citizens,
      providers, and public health investigators.
AB  - Access to epidemiologic data is critical to public health practice.
      Unfortunately, most published data are out of date and live databases are
      inaccessible because of issues of confidentiality, varying user needs, cost,
      security concerns, and other reasons. EpiQMS is a Web-based application that
      allows exploratory, statistical, and geographic analysis of public health data.
      Tables, graphs, and maps with adjustments for small areas are available at three
      levels: (1) the general public, (2) public health and medical practitioners, and
      (3) epidemiologists and health officers. The difference in each level is with
      respect to the presentation of small cell sizes and small geographies as set by
      the data set custodians.

PMID- 15156623
TI  - Development and evaluation of public health informatics at University of
      Washington.
AB  - Public Health Informatics (PHI) education began at the University of Washington
      (UW) with a Summer Institute in 1995. The Biomedical and Health Informatics
      graduate program, which is housed in the School of Medicine, is an
      interdisciplinary, multi-school program. It demonstrates the UW's cooperative
      efforts in advancing informatics, encompassing the schools of public health,
      medicine, nursing, dentistry, pharmacy, information and graduate schools in
      computer science. This article provides an overview of the developmental
      milestones related to activities in PHI and describes the evaluation strategy and
      assessment plan for PHI training at the UW (http://phig.washington.edu).

PMID- 15156624
TI  - Developing a public health Web site: the Los Angeles County experience.
AB  - The use of the Internet in public health practice is becoming increasingly
      widespread. The Internet is an important tool for supporting the mission and core
      functions of local health departments. However, most local health departments
      have limited resources and technical capacity to develop, deploy, and encourage
      use of large and complex Web sites. In Los Angeles County, the local health
      department was able to build and expand public health information systems on the
      Internet with a limited investment of financial and technical resources. The
      development process, key functions, and key factors in the success of this effort
      are described.

PMID- 15156625
TI  - Public health information systems: from promise to practice.

PMID- 15156626
TI  - Learning from clients: an opportunity for sexually transmitted disease programs.
AB  - This article summarizes sexually transmitted disease (STD) knowledge, health care
      seeking behaviors, and perceived advantages to seeking care from the perspective
      of 397 STD clinic clients interviewed between 1997 and 1999 in three northeastern
      cities. More than half reported a prior STD. Mean days delay in seeking treatment
      was 10.8. Reasons for delay included lack of knowledge especially about symptoms
      (44%) and inconvenience, especially clinic hours (46%). Major disadvantages to
      receiving care centered around embarrassment and stress (24%). Programs need to
      develop more intensive counseling for repeat clients, offer more flexible hours,
      address sources of stress inherent in their services, and develop better
      marketing strategies. Successful behavioral interventions, behavioral training,
      and creative approaches from the popular literature may be helpful.

PMID- 15156627
TI  - Consent for prenatal testing: a preliminary examination of the effects of named
      HIV reporting and mandatory partner notification.
AB  - The effect of named reporting and mandatory partner notification in New York
      State on the rate of consent for prenatal HIV testing was examined by
      retrospective chart review. In the six months prior to the introduction of
      mandatory partner notification and named reporting, 318/328 patients (96.95%)
      accepted HIV testing. In the six months after implementation, 303/305 patients
      (99.34%) accepted HIV testing. Although limited in power, no significant decline
      in the rate of consent for testing or the number of patients receiving testing
      was detected. [RR 1.02 (1.00 < RR < 1.05)].

PMID- 15156628
TI  - Public health worker competencies for emergency response.
AB  - Emergency preparedness is an expectation of public health organizations and an
      expectation of individual public health practitioners. Organizational performance
      standards for public health agencies have been developed during the last several
      years, providing a foundation for the development of competency statements to
      guide individual practice in public health program areas, like emergency
      response. This article provides results from a project that developed emergency
      preparedness and response competencies for individual public health workers.
      Documentation of the qualitative research methods used, which include competency
      validation with the practice community, can be applied to competency development
      in other areas of public health practice.

PMID- 15156630
TI  - Tools for public health assessment in the twenty-first century.

PMID- 15156629
TI  - The credentialing of a population-based health profession.

PMID- 15156631
TI  - Advancing public health through the assessment initiative.
AB  - The CDC Assessment Initiative provided funds to six states to promote the
      development of innovative partnerships between traditional public health agencies
      and other public and private partners. Novel and creative approaches and methods
      of assessment were developed to monitor progress toward achieving measurable
      national, state, and community health objectives. In this article, the strategies
      and accomplishments of the participant states are summarized.

PMID- 15156632
TI  - Measuring 2010 national objectives and leading indicators at the state and local
      level.
AB  - This article examines to what extent data are typically available at the state
      and local level to track the Healthy People 2010 (HP 2010) objectives. It is
      estimated that there is a data source to track 56 percent of the relevant HP 2010
      objectives at the state level and only 33 percent of the objectives can be
      tracked at the county level. The main solution for tracking more objectives at
      the state and county level is to expand the number of questions and coverage of
      the BRFSS and YRBS.

PMID- 15156633
TI  - The Missouri experience in providing tools and resources to promote community
      assessment.
AB  - The Missouri Department of Health (MDOH) has dedicated staff that provides
      technical assistance to communities that are conducting assessments and
      intervention strategies to meet community health needs. The MDOH developed a web
      site that is designed to make health data easily available at the local level.
      The Missouri Hospital Association partners in the process by making funds
      available to communities that have proposed interventions in response to their
      community assessment. This article describes this public/private relationship and
      some of the state and local experiences.

PMID- 15156634
TI  - Evaluation of community health assessment in Kansas.
AB  - This article evaluates the status of community health assessment in Kansas. It
      describes community characteristics associated with community health assessment
      completion, factors contributing to success, as well as barriers and limitations
      that prevented Kansas communities from initiating a community health assessment
      or completing the process. Survey findings show that certain community
      characteristics such as interagency cooperation, history of success at problem
      solving, and shared decision-making power are strongly associated with completion
      of a community health assessment. Results also indicate that factors such as lack
      of leadership, money, and time as well as poor functioning coalitions may hinder
      the completion of community health assessment.

PMID- 15156635
TI  - Use of a behavioral risk survey by employers to identify leading health problems
      among employees and their dependents.
AB  - In an effort to identify high-burden health conditions among employees and their
      families for worksite, community, and health care quality improvement
      interventions, The Mid-America Coalition on Health Care, with assistance from the
      Kansas Department of Health and Environment, conducted a broad behavioral risk
      survey among a random sample of employees of eight participating employers and
      their family members. By working with an established coalition of businesses,
      providers, payers, and other entities with a stake in controlling health care
      costs, state public health officials were able to assist the business community
      to adopt an acceptable approach to assessment of health risk and a community
      approach to risk reduction.

PMID- 15156636
TI  - Recommendations for addressing quality and health assessment initiatives in
      Minnesota.
AB  - A recent priority of the Assessment Initiative in Minnesota has been to develop
      recommendations for addressing quality and health assessment activities in the
      state. These recommendations consist of a comprehensive array of issues, most of
      which where there was fairly strong consensus and a few of which where there were
      differing perspectives among key stakeholders. There are some significant
      opportunities for advancing quality and health assessment activities in Minnesota
      in the context of state and national programs in health care and public health.

PMID- 15156637
TI  - Linking birth certificates with Medicaid data to enhance population health
      assessment: methodological issues addressed.
AB  - This study linked birth certificates with Minnesota Medicaid deliveries in order
      to identify Medicaid births. This article describes the link between methodology
      and results. Medicaid claims from 1997 were used to identify women with a
      delivery code. Identifiers for these women were linked to birth certificate
      files, with a match rate of 93.2 percent. Women's match status did not differ by
      maternal age. Women in some border counties matched at much lower rates than the
      rest of the population. The methodology was effective in linking Medicaid and
      birth certificate data and will be implemented as a data linkage protocol for
      Minnesota.

PMID- 15156638
TI  - The process to develop a meaningful community health assessment in New York
      State.
AB  - Conducting and producing a meaningful Community Health Assessment (CHA) is an
      important and essential public health service and a mandatory biennial activity
      for New York State's (NYS) Local Health Departments. The Assessment Initiative
      project has allowed the NYS Department of Health to better understand and
      identify strategies to strengthen CHAs and to develop training, education, and
      technical assistance programs. The Assessment Initiative project has benefited
      from participation, coordination, and sharing of resources and expertise with
      other community health improvement initiatives in NYS, including those that
      emphasize collaborative approaches to health improvement, workforce development,
      and expanding access to data.

PMID- 15156639
TI  - Measuring the impact of a public health data training program.
AB  - In spring and fall of 2000, 109 community health professionals participated in
      "Public Health Data: Our Silent Partner," a training program developed by the
      Centers for Disease Control and Prevention (CDC). The two-day training was
      offered four times in different locations in New York State in response to local
      health departments and community partners identifying a need for data analysis
      training. Participants completed evaluations during the training, and they were
      surveyed within a year of completing the training. This article discusses the
      impact of the training and suggests ways to increase the value of the training.

PMID- 15156640
TI  - Public health surveillance approaches in Oregon's Medicaid population.
AB  - The development of methods for public health surveillance in Medicaid populations
      is an important goal for public health practice. In Oregon, we developed
      approaches to case finding using claims and self-reported data obtained from the
      Medicaid beneficiary population. Disease rosters, derived from claims data, form
      the basis for analyses pertaining to particular health conditions. Self-reported
      information obtained through a telephone survey forms the basis for analyses
      pertaining to behavioral risk factors, disease history, and other information not
      available in claims data. We also describe some projects in which we plan to use
      combined claims and survey data. We describe our experiences with using these
      techniques and provide examples from projects in progress or planned. Our initial
      experiences suggest that these approaches enhance our ability to conduct public
      health surveillance in Oregon's Medicaid population.

PMID- 15156641
TI  - Tracking Oregon Medicaid patients' enrollment and health utilization patterns.
AB  - The Oregon Medicaid program consists of various sub-programs with different
      eligibility requirements and multiple health care delivery systems.
      Administrative events, such as the loss of Medicaid eligibility or a change in
      health plan enrollment, can cause disruptions in the continuity of medical care
      and may contribute to missed opportunities to provide appropriate medical
      services, including preventive care. Thus, in order to improve public health
      surveillance and describe the health care utilization patterns of Oregon's
      Medicaid beneficiaries, a standardized approach was developed to track the
      enrollment status of Medicaid patients for extended periods of time.

PMID- 15156642
TI  - Assessment partnerships between managed care and public health: the Massachusetts
      experience.
AB  - This article explores factors that facilitate or impede data sharing and linkage
      collaborations between state public health agencies and managed care
      organizations (MCOs). The exploration is based upon a review of both recent
      literature and the four years' experience of the Massachusetts Health Assessment
      Partnership (MHAP). MHAP has undertaken six collaborative data sharing and
      linkage projects that have involved diverse topics and methods. This article
      summarizes both exogenous and endogenous factors that have affected MHAP as a
      successful collaboration and indicates those factors that might be replicated in
      future collaborations between public health agencies and MCOs in other locations.

PMID- 15156644
TI  - Evaluation of mandated memoranda of understanding between local health
      departments and Medicaid managed care plans.
AB  - The success of mandating memoranda of understanding (MOU) in promoting
      collaboration between Medicaid managed care (MCMC) plans and local health
      departments (LHDs) was examined in this research project. The mandate resulted in
      MOUs that contributed to increases in collaborative activities, increased
      perceived quality of health care, and successful management of reimbursement to
      LHDs. Factors associated with success included a local initiative type of health
      plan, longer length of time that the MOUs were in place, and higher
      interorganizational collaborativeness. Concerns related to the MOU approval
      process and lack of contribution of the MOUs to quality of public health services
      were identified. MOUs promote collaborative relationships between MCMC plans and
      LHDs on health care issues important to both sectors.

PMID- 15156643
TI  - Quality oversight for Medicaid managed care plans: impact on providers.
AB  - The purpose of this study was to describe managed care organization (MCO)
      provider interactions around quality monitoring in Medicaid managed care. Heads
      of ambulatory pediatrics in institutions and private providers in offices in New
      York City (NYC) responded to questions regarding several forms of MCO-provider
      communications around quality. It appears that the current quality monitoring
      review process undertaken by managed care plans in provider sites in NYC is
      duplicative and overlapping. Feedback from the quality reviews is not being
      received by the providers who are giving care and incentives/disincentives are
      not felt. These constitute severe limitations to the current system of quality
      oversight.

PMID- 15156645
TI  - Public health competencies required by managed care organizations.
AB  - The authors developed a list of population-based public health competencies. They
      surveyed the chief executive officer, chief medical officer, and chief quality
      control person at a randomly selected group of managed care organizations drawn
      from the membership of the American Association of Health Plans. The authors
      asked them to rank those competencies that were essential for them in their work
      with their organization. The authors identified both the most commonly required
      competencies across all groups and the most essential for each specific job in
      the managed care organization. This article discusses these competencies and
      their implications for those who are responsible for ensuring that graduates have
      achieved required competencies.

PMID- 15156646
TI  - Assessment, program planning, and evaluation in population-based public health
      practice.
AB  - Public health practitioners in Minnesota developed and implemented a population
      based public health practice model for community assessment, program planning,
      and evaluation. The ultimate goal of this process is improvement in population
      health. Major challenges to the implementation of a population-based model are
      addressed through the use of a theory of action; interventions at community,
      systems, and individual levels; and intermediate evaluation indicators. Examples
      of resulting changes in public health practice are described.

PMID- 15156647
TI  - A model approach for developing effective local public health policies: a North
      Carolina County responds to large-scale hog production.
AB  - When intensive livestock operations or other large-scale industrial facilities
      pose a threat to public health, elected officials have a responsibility to ensure
      that the public's health is protected. Local policymakers need to guarantee that
      the process offers ample opportunity for balanced community input, and that the
      policy base is sound and well reasoned. Government officials need to manage the
      process so that balanced perspectives are presented and respectfully heard. A
      model approach, similar to the one described here, will assist local officials in
      crafting reasonable health rules that protect the public health and that diverse
      stakeholders can accept.

PMID- 15156648
TI  - Interagency collaboration in seven North Carolina counties.
AB  - This article describes the collaborative efforts of seven North Carolina counties
      involved in a home visitation program for new mothers. It explores factors that
      facilitated and impeded collaboration. Program staff reported strong leadership,
      shared vision, a heterogeneous mix of partners, establishment of trust, a
      positive attitude, role delineation, and open communication to be factors
      contributing to successful collaboration. Lack of guidance about how to
      collaborate, competition between programs and categorical funding, restrictive
      confidentiality policies that limit cross-agency access to information, and lack
      of time and energy were major barriers to achieving integrated service delivery
      systems.

PMID- 15156649
TI  - Legal options for achieving public health outcomes.
AB  - To achieve desired public health outcomes, state agencies can choose among
      several legal mechanisms; however, no "best practice" guidelines are available to
      help them choose the most effective mechanism for a given situation. This article
      offers such guidance by comparing the relative advantages and disadvantages of
      laws, regulations, policies, and contracts. Factors compared include flexibility,
      the need for legislative involvement, the nature of the rulemaking process,
      enforceability, ability to reach target populations, and generalizability.
      Contracts, in particular, are described as an effective but underutilized
      mechanism for achieving successful public health outcomes.

PMID- 15156650
TI  - The determination of organization stakeholder salience in public health.
AB  - Because interorganizational arrangements are encouraged as necessary to meet
      public health goals, it is critical for the managers of public health services at
      any level to consider stakeholder theory from an organizational perspective.
      Public health managers are responsible for the stakeholders in public health as
      well as public health as a stakeholder in other organizations. This article
      presents an innovative tool for the determination of organization stakeholder
      salience that assists managers in establishing priorities for interorganizational
      relationships during strategic planning and day-to-day decision making.

PMID- 15156652
TI  - [Pinching].

PMID- 15156653
TI  - [Can homeopathy survive the test of science?].

PMID- 15156651
TI  - [Inguinal herniation in foals. Literature review and a case report].
AB  - A literature review is given concerning the occurrence, clinical signs and
      possible treatment of the different types of inguinal herniation in foals. A six
      week old filly with a reducible inguinal hernia is described in detail.

PMID- 15156654
TI  - [Young perennial ryegrass staggers in a dairy herd].
AB  - Ryegrass staggers was diagnosed in a group of young stock on a dairy farm in the
      Netherlands. The cattle were fed on ryegrass hay originating from a farm in the
      region. The typical clinical signs observed in this herd were difficulty in
      rising, hypermetria of especially the front legs, incoordination, and tremors of
      the head and neck muscles. The morbidity of the illness was about 80 percent and
      there was no mortality. Four weeks after withdrawal of the hay, the animals
      recovered completely. The diagnosis was confirmed by demonstrating high
      concentrations of Lolitrem-B (1.7 ppm) in the hay. This neurotoxin is usually
      produced by the endophyte Neotyphodium lolii with which ryegrass may be infected.
      This is the first case of ryegrass staggers in cows reported in the Netherlands
      since 1992.

PMID- 15156655
TI  - [Companion Animal Parasite Council (CAPC), USA. Independent advisory council for
      controlling internal and external parasites who pose a public health threat to
      humans and animals].

PMID- 15156656
TI  - [Symposium 'healthy animals, healthy people'].

PMID- 15156657
TI  - [Tulathromycin, a new antibiotic for farm animals].

PMID- 15156658
TI  - [Autochthonous babesiosis in dogs in the Netherlands?].

PMID- 15156659
TI  - [Homeopathic treatment based on thorough examination].

PMID- 15156660
TI  - [More 'Bumblebee-o-pathic' reasoning].

PMID- 15156661
TI  - [Treatment of CVMP-affected fibrosarcoma not supported].

PMID- 15156662
TI  - [Incidence of 'recognized and admitted cases'].

PMID- 15156663
TI  - [European animal passport replaces the Dutch version in July 2004].

PMID- 15156664
TI  - Asian bird flu.

PMID- 15156665
TI  - Group's report finds states' bio-preparedness lacking.

PMID- 15156666
TI  - CPR compressions-first protocols being tested.

PMID- 15156667
TI  - Data deluxe: Texas system puts product suite to good use.

PMID- 15156668
TI  - Not your emergency: accepting your limitations.

PMID- 15156669
TI  - The power of peers.

PMID- 15156670
TI  - Failure on the board.

PMID- 15156672
TI  - Recent events underscore staging policies.

PMID- 15156671
TI  - Incomplete spinal cord injuries.

PMID- 15156674
TI  - EMS associations: more than just alphabet soup?

PMID- 15156673
TI  - Quarantine angst. What it might mean for EMS, public health.

PMID- 15156675
TI  - A basic approach to prehospital management of penetrating trauma.

PMID- 15156676
TI  - Selective immobilization. Current research and practice.

PMID- 15156677
TI  - Immobilization errors in EMS.

PMID- 15156678
TI  - Selective spinal immobilization.
AB  - As medicine moves further along toward science, it is important that EMS makes
      changes in practice based on sound research. NEXUS and other similar projects are
      examples of how to apply that principle: Examine the problem, suggest a solution
      and measure the effect. As more data are collected, I believe we will learn that
      EMTs can safely apply the same assessment principles in the field that are used
      in the hospital, and our patients will ultimately benefit from both.

PMID- 15156679
TI  - Asthma. An acute and chronic problem for EMS.

PMID- 15156680
TI  - Ambulance A & P. Steering, suspension and tires.

PMID- 15156681
TI  - Preplanning for special events.

PMID- 15156682
TI  - EMS bike deployment.

PMID- 15156683
TI  - Preventing bike injury--a primer.

PMID- 15156684
TI  - Heart hazards, heart health.

PMID- 15156686
TI  - To quit or not to quit.

PMID- 15156685
TI  - Watch your back.
AB  - Be aware of how you lift, and take corrective action to lift and move in a safe
      manner each and every time. It is never too late to practice safe lifting
      techniques. Avoid hasty activities and twisting motions. Consciously practice
      proper lifting and moving functions every time you lift or move, and remain aware
      of your posture when you are sitting or lying. Your spine will appreciate the
      consideration.

PMID- 15156687
TI  - Worker wellness.

PMID- 15156688
TI  - [Prevention in pediatrics].
AB  - Recent achievements in clinical research and progress in molecular biology and
      genetics have opened new perspectives in maintaining health and preventing
      disease. Due to its specialty, paediatrics may be particularly effective in
      utilizing these possibilities. Modern therapeutic procedures may themselves be
      preventive, in so far as they can ward off complications and late sequelae. In
      addition to application of new methods, physicians and district nurses dealing
      with children should go on with unchanged thoroughness in their traditionally
      successful preventive measures, such as infant care, vaccination, vitamin D
      prophylaxis, and others. Since health state of infancy and childhood have a
      significant influence on the quality of life in adulthood, support of paediatric
      health care and promoting a favourable social background for preventive
      activities will certainly have long-term advantages.

PMID- 15156689
TI  - [Prognosis for the fetus with congenital heart defects in the era of modern
      diagnostics and therapeutics].
AB  - BACKGROUND: Prenatal detection of structural heart diseases and rhythm
      disturbance has become possible using echocardiography. Authors have already
      documented the high diagnostic accuracy of intrauterin diagnosis of heart
      diseases in our country as well. AIM OF THIS STUDY: To examine the prognosis of
      fetal cardiac diseases diagnosed by echocardiography in the institute between
      1985-2001. METHODS: The prognosis of 223 (6.3%) cardiac anomalies found in 3468
      fetal echocardiograms was assessed by postnatal echo/surgery/or autopsy. RESULTS:
      The authors detected cardiac anomalies in 153, rhythm disturbance in 70 fetuses.
      They could follow (mean 4.2 yrs) the 83% of patients by postnatal echo/surgery or
      autopsy. They lost 46 pts (36%) by elective termination, intrauterine death, or
      during the postnatal period. 83% of these pts had hypoplastic left heart
      syndrome, fibroeleastosis, or aortic stenosis. Right heart anomalies (tetralogy
      of Fallot, critical pulmonary stenosis etc.) showed good prognosis with early
      surgical or catheter intervention. Isolated fetal supraventricular tachycardias
      can be successfully treated prenatally, and fetal complete heart block by
      emergency postnatal permanent pacemaker implantation. CONCLUSIONS: Fetal
      echocardiography must be considered in our country also such a method which can
      influence the natural history of fetal heart diseases. The result of infant
      cardiac surgery also dramatically improved, so we think this knowledge is very
      important during the counselling.

PMID- 15156691
TI  - [Clinical significance of blood glucose levels in the pathogenesis of
      (atherosclerotic) macroangiopathy].
AB  - Numerous authors suggested postprandial blood glucose elevation as a significant
      contributor in development of macroangiopathy. Epidemiological studies and animal
      experiments delivered supportive data about causal relationship between
      postprandial hyperglycaemia and macroangiopathy in type 2 diabetes. Interestingly
      there is no chronological correlation between presence of hyperglycaemia and
      development of macroangiopathy neither in type 2, nor in type 1 diabetics. Strict
      metabolic control does not result in slowing progression of macroangiopathy
      (glucose paradox). Premature macroangiopathy documented in the prediabetes phase
      of type 2 diabetes is strongly related to presence of insulin resistance,
      hyperinsulinaemia, high blood pressure, and dyslipidaemia; development of
      atherosclerosis in advanced stage of type 1 diabetes is also rather associated
      with presence of high blood pressure and dyslipidaemia but not that of
      hyperglycaemia. With regard to role of postprandial hyperglycaemia it should be
      emphasized, that not the postprandial blood glucose elevation per se, but rather
      the postprandial complex metabolic cluster (hyperinsulinaemia,
      hypertrygliceriadaemia, etc) is supposed to be related with development of
      macroangiopathy in patients with metabolic syndrome and type 2 diabetes.

PMID- 15156690
TI  - [Effect of ACE gene polymorphism on carbohydrate metabolism, on oxidative stress
      and on end-organ damage in type-2 diabetes mellitus].
AB  - ACE gene insertion/deletion (I/D) polymorphism is a well-known risk factor of
      hypertension, cardiovascular diseases and progression of diabetic nephropathy. In
      carriers of allele D, serum level of angiotensin-II is higher, which can be
      associated with increased oxidative stress and subsequent endothelial damage.
      Albuminuria is a sensitive marker of endothelial damage, while serum activity of
      the enzyme gamma-glutamyl transferase--that plays important role in the
      antioxidant defense--may refer to the level of oxidative stress. The present
      paper reports on a cross-sectional clinical study, where authors have examined on
      the relation between ACE gene insertion/deletion polymorphism and carbohydrate
      metabolism, hypertension as well as albuminuria in type 2 diabetics (n = 145). In
      patients carrying allele D, fructosamine levels were significantly higher (p =
      0.007) than in carriers of allele I. Patients with II + ID genotypes and those
      who were treated with insulin took more antihypertensive drugs than the ones with
      II genotype or orally treated (p = 0.015). They found a significant association
      between genotype and fructosamine level (p = 0.023). Association between genotype
      or modality of treatment of diabetes (oral vs, insulin) and combined treatment of
      hypertension (number of antihypertensive drugs) was of borderline significance.
      They found that fructosamin level of patients receiving ACE inhibitor was lower
      than that of patients not receiving ACE inhibitors. In patients with allele D,
      they have also found higher activity of gamma-GT and higher albuminuria. From
      this results and data of the literature the authors conclude that because of
      insulin resistance (in connection with the presence of allele D), these patients
      tend to have a worse metabolic state, more advanced glycation products, due to
      which oxidative stress and endothelial cell damage may develop. As albuminuria
      and activity of gamma-GT were both found higher in patients with allele D, and
      our patients did not suffer of any hepatic disease, authors take the consequence
      that gamma-GT is a marker of the oxidative stress caused by allele D. Endothelial
      damage may explain that these patients take a higher number of antihypertensive
      combination. Based on this, D allele may contribute--via increased glycation and
      oxidative stress--to the target organ damage in type 2 diabetes.

PMID- 15156692
TI  - [Therapy in acromegaly].

PMID- 15156693
TI  - [Therapy in tuberculosis].

PMID- 15156694
TI  - [Life and works of Gabor Veza, the first Hungarian secretary of public health].

PMID- 15156695
TI  - [Clinical aspects of hypothalamo-hypophyseal disorders].

PMID- 15156696
TI  - Improving the workplace environment to promote quality of care.
AB  - To improve patient care while containing costs, some hospitals and long-term-care
      facilities are redesigning their workplace environments--physically and/or
      procedurally--to attract nurses and their colleagues and make them places where
      they want to stay and work.

PMID- 15156697
TI  - Medicare Advisory Commission focuses on quality of care, patient safety.
AB  - The issue of quality of care dominated the new report on Medicare payment policy
      of the Medicare Payment Advisory Commission, submitted to Congress last month.
      The report notes that Medicare beneficiaries--mirroring trends in care for the
      rest of the population--face "significant gaps between care known to be effective
      and the care delivered"--especially where patient safety issues are concerned.

PMID- 15156698
TI  - Lack of financial incentives slows hospitals' jump to meet leapforg safety
      standards.

PMID- 15156699
TI  - Hospital emergency department diversion rates slow down.

PMID- 15156700
TI  - CT screening--whole-body and targeted.
AB  - At present, the Australasian College of Physical Scientists and Engineers in
      Medicine does not support the practice of self-referred whole-body CT screening
      of asymptomatic patients because: The procedure involves a non-trivial radiation
      dose, which assumes even greater significance in the context of an ongoing
      screening programme; There is a high likelihood of false positives requiring
      further intervention with its attendant risks; and There is no proven evidence to
      date that early detection of life-threatening disease by CT has a significant
      positive effect on patient outcome. The ACPSEM will continue to monitor
      scientific studies concerning this procedure.

PMID- 15156701
TI  - Use of water-equivalent plastic scintillator for intravascular brachytherapy
      dosimetry.
AB  - Beta irradiation has recently been investigated as a possible technique for the
      prevention of restenosis in intravascular brachytherapy after balloon dilatation
      or stent implantation. Present methods of beta radiation dosimetry are primarily
      conducted using radiochromic film. These film dosimeters exhibit limited
      sensitivity and their characteristics differ from those of tissue, therefore the
      dose measurement readings require correction factors to be applied. In this work
      a novel, mini-size (2 mm diameter by 5 mm long) dosimeter element fabricated from
      Organic Plastic Scintillator (OPS) material was employed. Scintillation photon
      detection is accomplished using a precision photodiode and innovative signal
      amplification and processing techniques, rather than traditional photomultiplier
      tube methods. A significant improvement in signal to noise ratio, dynamic range
      and stability is achieved using this set-up. In addition, use of the non
      saturating organic plastic scintillator material as the detector enables the
      dosimeter to measure beta radiation at very close distances to the source. In
      this work the plastic scintillators have been used to measure beta radiation dose
      at distances of less than 1 mm from an Sr-90 cardiovascular brachytherapy source
      having an activity of about 2.1 GBq beta radiation levels for both depth-distance
      and longitudinal profile of the source pellet chain, both in air and in liquid
      water, are measured using this system. The data obtained is compared with results
      from Monte Carlo simulation technique (MCNP 4B). Plastic scintillator dosimeter
      elements, when used in conjunction with photodiode detectors may prove to be
      useful dosimeters for cardiovascular brachytherapy beta sources, or other
      applications where precise near-source field dosimetry is required. The system
      described is particularly useful where measurement of actual dose rate in real
      time, a high level of stability and repeatability, portability, and immediate
      access to results are prime requirements.

PMID- 15156702
TI  - EEG coherence changes between right and left motor cortical areas during
      voluntary muscular contraction.
AB  - It is known that movements of the right side of the body are controlled by the
      left motor cortex of the brain. The aim of this study is to evaluate the
      contribution of right motor cortex of the brain in the central motor control of
      right-sided muscle contraction. EEG/EEG coherence analysis has been used to
      determine the functional coupling between the right and left motor cortical areas
      in twenty normal volunteers, during maximum voluntary contraction (MVC) and 50%
      MVC of right Adductor Pollicis muscle (APM). It shows that the maximum mean
      coherence values were: 0.751 during MVC at 10 and 12 Hz, and 0.274 during 50% of
      MVC at 22 Hz. The minimum mean coherence values were: 0.716 during MVC at 48 and
      50 Hz, and 0.242 during 50% MVC at 34 Hz. The high coherence values obtained
      during MVC, and to a lesser extent during 50% of MVC, could be attributed to the
      need of recruitment of both motor cortical areas during the decision phase of
      central motor control of voluntary muscular contraction. The "will" to perform
      maximum voluntary contraction could be a major factor, which contribute to the
      higher coherence values obtained during MVC than these associated with 50% of
      MVC.

PMID- 15156703
TI  - Comparison of measured and calculated radiotherapy doses in the chest region of
      an inhomogeneous humanoid phantom.
AB  - Errors in dose calculation by treatment planning computers are known to arise
      when calculation algorithms do not account for electron disequilibrium near
      interfaces between tissues of different density. The accuracy of a treatment
      planning system (Plato, Nucletron International BV) was investigated for two
      treatments in the chest region: tangential 6 MV photons to the chest wall and
      opposed AP-PA 18 MV photon fields to the mediastinum. Thermo-luminescent
      dosimeters were used to measure dose at 40 sites in the chest of a humanoid
      phantom (Rando, Alderson Associates). Measurements were compared with point doses
      calculated using two different versions of the Plato external beam calculation
      software: RTS 1.8 and the newer RTS 2.2. Measured and calculated doses differed
      by 3% or more at more than one quarter of all sites. The greatest discrepancies
      occurred for points located in lung, which were generally overestimated. The
      maximum discrepancies for the 6 MV tangential breast irradiation were 8.5% for
      RTS 1.8 and 3.5% for RTS 2.2. For the 18 MV opposed field irradiation, the
      maximum discrepancies were 11.4% and 8.1% respectively. RTS 2.2 was more accurate
      than RTS 1.8, with smaller mean and maximum discrepancies.

PMID- 15156704
TI  - Photography of the living human cornea in ultraviolet light.
AB  - The living human cornea was photographed in ultraviolet light of bandpass 315-326
      nm produced by a xenon arc light source and multilayer interference filters. The
      image was captured on black and white film using a quartz fluorite lens. The
      photographs revealed structural details not seen in visible wavelengths.

PMID- 15156705
TI  - A thermoluminescent dosimetry postal dose inter-comparison of radiation therapy
      centres in Malaysia.
AB  - A thermoluminescent dosimetry (TLD) postal dose inter-comparison was carried out
      amongst radiotherapy centres in Malaysia. The aim of this TLD inter-comparison
      was to compare the uniformity involved in the measurement of absorbed dose among
      the participating centres. A set of 5 TLD chips placed within acrylic trays were
      mailed to all participating centres for irradiation to an absorbed dose to water
      of 2 Gy. Measurements were made for 6 MV and 60Co photon beams. Results show an
      agreement of +/- 5% for all but three radiotherapy centres. The ratios of the TLD
      readings to that of the reference centre are comparable with other
      national/regional dose inter-comparisons. The importance of a proper ongoing
      quality assurance program is essential in maintaining the consistency and
      uniformity of doses delivered.

PMID- 15156706
TI  - Production of electron trees with a clinical electron accelerator.
AB  - Simple methods for generating 'electron trees' (patterns of charge deposition and
      discharge in a low-conducting medium) with a modified clinical electron
      accelerator are described.

PMID- 15156707
TI  - The calibration of a Scanditronix-Wellhofer thimble chamber for photon dosimetry
      using the IAEA TRS 277 code of practice.
AB  - This note investigates the calibration of a Scanditronix-Wellhofer type FC65-G
      ionisation chamber to be used in clinical photon dosimetry. The current
      Adaptation by the Australasian College of Physical Scientists and Engineers in
      Medicine (ACPSEM) of the IAEA TRS 277 dosimetry protocol makes no provision for
      this type of chamber. The absorbed dose to air calibration coefficient ND was
      therefore calculated from the air kerma calibration coefficient NK using the
      formalism of the IAEA TRS 277 protocol and it is shown that the value of the
      correction factor kmkatt for the FC65-G chamber is identical to that of the NE
      2571 chamber. ND was also determined experimentally from a cross calibration
      against an NE 2571 dosimetry. It was found that there is a good correspondence
      between the calculated and measured values. To establish to what extent the
      ACPSEM Adaptation can be used for the FC65-G chamber, values for the ratio of
      stopping powers in water and air (Sw,air)Q and the perturbation correction factor
      pQ were calculated using the TRS 277 protocol. From these results it is shown
      that over the range of beam qualities TPR20,10 = 0.59 to TPR20,10 = 0.78 the
      Adaptation can be used for the FC65-G chamber.

PMID- 15156709
TI  - Patient falls from hospital window: questionable nursing care? Case on point:
      Russ v. Titus Hospital District, 2004 WL100403 S.W.3d--TX.

PMID- 15156708
TI  - Rude, arrogant & incompetent RN alleges retaliatory termination.

PMID- 15156710
TI  - TX: Dr.'s expert opinion medical report deficient: Suit v. Visiting nurses over
      negligent infusion fails.

PMID- 15156711
TI  - TX: nursing home brings mandamus v. judge: were decubitius ulcers 'cause' of
      pt.'s death?

PMID- 15156712
TI  - Student nurse punctured sciatic nerve: was hospital liable? Case on point: Lovett
      v. Lorain Community Hospital, 2004 WL239927 N.E.2d --OH.

PMID- 15156713
TI  - Detection of ketosis and monitoring of diabetic ketoacidosis.

PMID- 15156714
TI  - Novel syndromes of ketosis-prone diabetes: implications for management and
      medical economics.

PMID- 15156715
TI  - Role of blood ketone testing in sick-day management.

PMID- 15156717
TI  - [75 years of the Polish Society of Surgical Orthopedics and the Polish Society of
      Orthopedics and Traumatology, 1928-2003].

PMID- 15156716
TI  - Challenges and opportunities in diabetes care: improving outcomes with education,
      disease management, and new technologies.
AB  - In summary, point-of-care testing of beta-hydroxybutyrate concentrations, whether
      in the home or the physician's office, augments blood glucose monitoring and
      serves as an important tool for the routine management of diabetes. Through the
      timely use of beta-hydroxybutyrate monitoring, patients may be able to avert
      episodes of DKA, preventing significant morbidity and potential mortality.
      Furthermore, health care systems can be spared the substantial expense of
      hospital treatment of DKA and its consequences. The challenge for diabetes
      professionals comes with the need to establish blood ketone monitoring a routine
      part of diabetes care, similar in importance to blood glucose monitoring for
      patients with insulin-treated diabetes.

PMID- 15156721
TI  - Language dynamics and change. Introduction to linguistic diversity in
      anthropological perspective.

PMID- 15156722
TI  - Universals of language maintenance, shift and change.
AB  - Since Greenberg the recognition of linguistic universals has been the backbone of
      language typology. Earlier Garvin had already divided universals into absolute
      and potential ones, the former uncontested cornerstones of linguistic theory, the
      latter commonly accepted generalizations among experienced professionals. The
      'universals' to be discussed here are of the latter type: tried and tested
      principles of language maintenance and of language change, whose applicability
      has been established in numerous language contact and conflict situations in
      different communities. Among the principles displayed and discussed are the
      following: Fishman's 'intergenerational dislocation' of language reproduction;
      Haugen's 'dialect fragmentation' of languages vs. Garvin's 'unification' and
      standardization; Fishman's claim of the complementary distribution of language
      functions as a guarantee of stable bilingualism; Wolck's disparate distribution
      of minority language maintenance along the social scale. Evidence for those and
      some other 'universals' of language maintenance and change will be provided from
      a 30-year longitudinal survey of Quechua-Spanish bilingualism in Peru; from
      Seneca-English bilingualism in New York; from studies of diglossia in Scotland
      and North Germany, of German-Hungarian bilingualism in Hungary from the Ladin
      survey in Italy and the Sorbian Project in Germany, and from the EUROMOSAIC
      survey.

PMID- 15156723
TI  - Suggesting a new European language policy.
AB  - Conflict is the most intriguing aspect of contact linguistics. Throughout history
      ever since the Tower of Babel was left unfinished, contacts between speakers of
      different languages have unavoidably resulted in conflicts between speakers of
      those languages. Without any doubt, the European Union (EU)--above all after the
      decision to enlarge the community--has accepted the multidisciplinary symbolic
      function of language and culture as a basis for European political unification.
      Accordingly, European Union policy makers have had to analyze conflicts caused by
      monolingualism and multilingualism, all aspects of contact linguistics. Can these
      conflicts be solved, minimized or neutralized by strategies of language planning,
      language policies and language politics? Initial results of European language
      policy strategies permit at least a cautious measure of optimism and open broad
      perspectives for the future of a New Multilingualism which will be discussed in
      our contribution.

PMID- 15156724
TI  - Linguistic diversity, global paradigms and taken-for-grantedness.
AB  - In the first part of this paper taken-for-granted hypotheses in linguistic
      diversity are presented. In the second part the two constellations of globalized
      ideologies are described constituting paradigms that these hypotheses illustrate:
      competition and solidarity. In the third part, a condensed version of emerging
      globalized concerns is given. Sociolinguistics and anthropological linguistics
      are disciplines that increasingly theorize and analyze within the solidarity
      paradigm. It is suggested that a systematic uprooting of competition as taken-for
      granted grounding of scientific research should allow for the development of
      theorization and successful applications of solidarity ideologies. In short, in
      this paper, our multifaceted taken-for-grantedness is challenged in many ways:
      (1) competition is ideological and many social movements are unmasking it by
      articulating solidarity as a basis for ideologies, (2) difference is not
      necessarily divisive but it is so in pervasive competition, (3) proponents of the
      Nation-State as a model of social organization have vested interests in
      competition, (4) competition has not favored the articulation of common human
      grounds but globalization helps to raise concerns and articulate
      commonness/solidarity in difference.

PMID- 15156725
TI  - The history of linguistic anthropology as a device for a new integrated
      perspective.
AB  - The history of the emergence of linguistic anthropology helps us not only to
      reflect on the path-dependency of our own scientific categories, but also to
      enlarge our own perspective beyond these categories. The following paper tries to
      develop on the basis of Latour's network theory a new integrated perspective that
      reflects our own historical position in the network of constructing scientific
      facts, in the context of political problems, of social claims of objects that we
      are using in order to constitute our scientific field.

PMID- 15156726
TI  - Getting language rights, shifting linguistic traditions.
AB  - "Endangerment," "loss," "death," and related terms are increasingly familiar in
      descriptions of sociolinguistic changes now occurring at an unprecedented scale
      due to forces of globalization. They can serve both as names for shared concerns
      of linguists and anthropologists, and as descriptions of otherwise different
      scenes of social encounter, because they are subject to multiple uses and
      interpretations. This paper focuses on tacit, enabling assumptions of three
      distinct strategies for framing and redressing "threats" to marginalized
      languages and speech communities. Recognition of their ideological grounds helps
      develop a sharper sense of their different uses, and the different social
      saliences which linguistic descriptions can have in and for marginalized
      communities.

PMID- 15156727
TI  - The birth of new languages in contemporary Europe.
AB  - The birth of a language is a historical process, which develops through almost
      six stages corresponding to six main properties (genetic distance, geographical
      isolation, adoption of a writing system, elaboration of a literary koine,
      national consciousness, official status), which are specific to Western
      civilization and limited to our concern, i.e. the languages in contemporary
      Europe. The two last properties are the most important and conclusive in
      achieving the full status of language in contrast with dialect, speech, idiom,
      vernacular and so on. Consequently, in this perspective the birth of a language
      can be stated when its use is felt as a token of national identity and its
      official status is recognized by politic power. The history of some interesting
      cases during the 20th century, such as Luxemburgish, Feroese and Macedonian will
      throw a light on the possible future scenario of the languages of the Former
      Yugoslavia. Other disputed, although not so dramatic cases, like Sardinian,
      Aranese, Moldavian and Ruthenian, are dealt with together with recurrent topics
      on minority languages. The conclusion is that, unlike the worldwide tendency, the
      number of languages will probably increase within the greater European Union in
      the course of the 21st century.

PMID- 15156728
TI  - A phenomenological view of language shift.
AB  - Sociolinguistic studies of language shift have in their majority framed their
      research object in a horizon of theoretically received variables such as class,
      ethnicity, locality, attitudes etc. In spite of a limited usefulness of such
      conceptual variables, and of a recently emerging focus on agency, negotiation,
      and praxis the best results we obtain have not questioned in a coherent and
      theoretically sound manner the continuing hegemony of mechanistic-metaphorical
      models (language death, language suicide). In this paper I propose to examine
      language shift as a multifaceted phenomenon, joining in this respect work by
      other linguistic anthropologists researching similar areas. I specifically argue
      that by replacing vertical concepts such as age and generation, and dichotomous
      logics such as center and periphery with phenomenologically inspired concepts
      such as typifications, consociateship, contemporariness, and stream of
      consciousness we are in a better position to generalize about language shift
      dynamics. Data for this work is derived primarily from the Albanian speech
      communities of modern Greece, but also from other communities for comparative
      purposes.

PMID- 15156729
TI  - Language and identity--the Afrikaans community in the UK.
AB  - The role of language in the identity package of Afrikaans-speaking South African
      expatriates in the UK is investigated in this paper. A description of the
      community is provided and the domains of use of their first language identified.
      The main research problem is the relationship between language and identity in a
      diasporic community such as this. THE MAIN FINDINGS OF THE STUDY: In all modes of
      communication, the percentage of Afrikaans (in a bilingual relation with English)
      progressively decreased the closer the ties between the interlocutors became. The
      identification of 73% of all respondents with positive language-related
      statements correlated with 82% of the group's support for various types of
      cultural activities involving visiting South Africans. IN CONCLUSION: The mix of
      functions pointed to a more complex configuration of bilingual and monolingual
      domains, with some elements of a heterolocal cultural enclave, in which similar
      domain types are maintained in parallel, but with differences in actual context
      of usage.

PMID- 15156730
TI  - A contrastive view of Irish language dynamics.
AB  - This paper presents an analysis of the linguistic anthropology which underpins
      the language dynamics of two Gaeltacht (Irish-speaking) areas, Ros Muc in
      Conamara, Co. Galway and Rath Cairn in Co. Meath. This research highlights what
      could be considered a socio-linguistic paradox: the community (Rath Cairn) which
      engages more vigorously in language maintenance endeavors, and exhibits a greater
      awareness of language policy and of linguistic ideology among members of the
      community, fares less favorably in socio-linguistic terms to the contrasting
      community (Ros Muc) which has to endure a more challenging socio-economic climate
      than that of Rath Cairn. The relative socio-economic success of the Rath Cairn
      community appears to be masking a greater malaise of socio-cultural fragility and
      language endangerment. In contrast, the language obsolescence issues faced by the
      Ros Muc community, though superficially not as severe, are enmeshed in what would
      be considered more pressing issues of socio-economic marginalization.

PMID- 15156731
TI  - Population behaviors and language maintenance--a case of the Korean-speaking
      community in China.
AB  - With the regard to language maintenance, one of the most successful in over fifty
      of ethno-linguistic communities in China is the Korean community with more than
      two millions of Korean-speakers, in which there have been Regulations Regarding
      the Ethnic Language Use, and a maintenance-orientated and bilingual education
      system. However, language attrition comes to be occurring in the Korean community
      because more than two hundred thousands of Korean-speaking migrants have streamed
      from the Korean-rural community to the Chinese-urban community for the last
      twenty years. This paper, in urban-anthropological and sociolinguistic
      perspectives, is aiming at an analysis of the cause of population moves and the
      urbanization process of the Korean community as well as their impact on the
      language maintenance and bilingual education in the Korean community. It is
      mainly divided into four sections, namely, (1) the situation of Korean-speaking
      community; (2) the problem of language maintenance; (3) the impact of Korean
      speakers moves on language maintenance; (4) the impact of negative growth of
      population, and (5) the impact of uneven ratio of female population.

PMID- 15156732
TI  - Cultural implications of attitudes and evaluative reactions toward dialect
      variation in Croatian youth.
AB  - As a consequence of political changes and war, during the last decade the
      migration processes have been intensified and in comers from other parts of
      Croatia and neighbouring countries have moved to the town of Zagreb and have
      changed it considerably. These demographic changes have also had an influence on
      the language used in the area and on language attitudes towards the Standard
      Croatian, local vernacular and other dialectal varieties. The aim of this study
      is to explore the awareness that speakers, Croatian adolescents resident in
      Zagreb, have of their own language variety and their attitudes toward different
      other dialect varieties. The data were collected using the speech guise method
      and a questionnaire in order to assess both conscious and unconscious components
      of these linguistic evaluations. The results obtained once again confirmed the
      expected prestige of the Standard variety in terms of its speaker's alleged
      highest competence, but also its low standing as far as social attractiveness is
      concerned. Non-standard local varieties showed the exactly opposite trend,
      although the evaluation of native and immigrant adolescents differed
      considerably.

PMID- 15156733
TI  - Identity and transculture in Vice Versa.
AB  - Quebec's struggle between francophones and anglophones has deeply affected other
      immigrant communities' identitarian practices. Within Montreal's eighties and
      nineties nationalist environment some Italo-Quebecois worked as a bridge between
      the two groups through the transcultural magazine Vice Versa. The article
      presents some findings from a case study that looks at how Vice Versa challenged
      dominant perceptions of identity and its role in society. It assumes that
      identity is negotiated between individuals, that language and ethnicity are key
      factors for social mobility and symbolic power on the marketplace, and that these
      function through hegemony. Through its use of untranslated French, English and
      Italian and its articles' contents Vice Versa's discourse on transculture
      undermines the assumption that identity is necessary for social interaction and
      negotiates new categories that dissolve ethnic boundaries. Vice Versa is a unique
      example of the emergence of a counter-hegemonic movement questioning identity at
      its roots.

PMID- 15156734
TI  - Japanese attitudes towards foreign languages.
AB  - The purpose of this study is to clarify Japanese attitudes towards foreign
      languages based on the kinds and changes of TV and radio programs that aired on
      the Japanese national broadcasting station (NHK) between 1955 and 2000. Foreign
      language programs are classified into three groups according to their content: 1)
      cultivation, 2) education, or 3) communication. For Japanese people, foreign
      languages are the measures of intelligence and intellect. Studying a foreign
      language is considered a sign of intelligence whether or not it is used for
      actual communication. The number of foreign language programs has increased
      tremendously since 1965 in part because the global economy has brought many
      countries in such close contact. Since 1990, programs for the purpose of
      communication have increased because of the necessity to communicate with foreign
      people. Japanese attitudes towards studying foreign languages have been changing
      gradually from an intellectual purpose to a communication purpose.

PMID- 15156736
TI  - New concepts and words in post-Soviet Russia.
AB  - The research of Anglicisms in European languages is a part of the project
      supervised by the scholars from the University of Cologne. The adaptation of loan
      words in the Russian language possesses some social and cultural peculiarities in
      contrast to other European countries due to the drastic political changes and
      dynamic introduction of the market economy. The investigation is based on the
      linguistic and social analysis of Anglicisms, which were imported into Russian in
      the late 90-s and the beginning of the new millennium. The research focus is
      concentrated on the study of the most frequent terms circulating on the pages of
      professional (literary, business, political) and other mass media sources. Three
      groups of the latest borrowings are discussed: neutral terms, which have proved
      to be rather stable within 20 years; expressive fashionable neologisms with the
      restricted sphere of application and evaluative words revealing either Western
      cultural values or socially marked concepts, typical of post-socialism.

PMID- 15156735
TI  - How are speech styles elaborated for presenting individual personality while
      bearing in mind social norms? Certain cases in Beppu City, Oita Prefecture,
      Japan.
AB  - The purpose of this paper is to examine how speech styles are elaborated for
      presenting individual personality. Through the narratives of ten selected
      interviewees, some social norms internalised by them emerged. Age, status and
      career are associated to the joo/ge (upper/lower) and the senpai/koohai
      (senior/junior) relationships. Whether it is the first meeting and the length of
      relationship are associated to shin/so (intimacy/distance) and uchi/soto (in
      group/out-group). In particular the notion of shin/so takes a role for adjusting
      speech styles. According to the narratives of individual episodes, there are
      several factors of determination of speech style, which are not necessarily
      following social norms. The way of constructing relationships, keeping power
      relations, protection and so on are influenced by regional characteristics, which
      include factors of determination of speech style such as generation, gender,
      solidarity, and jibunrashisa (like myself, personality) and so forth.

PMID- 15156737
TI  - New concepts and new words--how do languages cope with the problem of neology?
AB  - It is a well-known fact that languages react differently when foreign words
      denoting new concepts have to be integrated into the native system. The procedure
      mostly depends on the degree of purism present in a linguistic community: some
      languages are rather open to foreign influences and do not demonstrate any
      special hostility towards new words which are easily accepted and adapted to the
      phonological and morphological systems of the receiving language. Languages,
      which have a strong puristic tradition, usually channel their borrowings into the
      loan translation field using internal word formation resources as a means of
      creating neologisms. Regardless of whether they are built of native elements or
      appear as loans, neologisms are necessarily the result of linguistic changes.

PMID- 15156738
TI  - Ethno-cultural heritage of the peoples of west Pamir.
AB  - The paper presents a study on the West Pamir communities (Badakhshan, Tajikistan)
      based on language data of the Pamir languages of East-Iranian origin. At present,
      the ethnic groups of the West Pamir: Shughni, Rushani, Bartangi, Roshorvi, Khufi,
      Ishkashimi and Wakhi are communities of the Ismaili Shia Islam faith. The
      underlying concept of the paper is that ethnic and cultural key-concepts take
      place in the origin of the traditional beliefs and rituals and can be reliably
      reconstructed from the vocabulary of a particular community. Pamir languages
      vocabulary of the Pamir ethnic communities that uses East and West Iranian
      culturally significant terms may serve as a basis for understanding the genesis
      of Pamir Ismailism, its particular way of absorbing external cultures, and its
      present specific form. The purely linguistic criteria, like temporal dimension
      (linguistic chronology), and geographic dispersion and mobility, are believed to
      be critical for linking etymology to broader socio-cultural development context
      of the Pamir communities socio-historical and cultural life. Contemporary social
      and linguistic dynamics in the relations between nation, religion and language in
      Tajikistan needs systematic research, and reasonable interpretation.

PMID- 15156739
TI  - What do names tell us about our former occupations?
AB  - The paper will analyze some linguistic, primarily onomastic evidence of still
      existent or extinct crafts and occupations within the framework of the former
      social structure. Many one time crafts became extinct in the course of time, but
      traces of their former diffusion and importance can be reconstructed from their
      onomastic, primarily, anthroponomastic reflections. Similar surnames motivated by
      occupation can be found all across Europe. Some surname statistics in various
      European countries are given in the paper.

PMID- 15156740
TI  - Cultural diversity in crossing the boundaries between human and animal in
      language--Germanic and Slavic similes and metaphors.
AB  - The paper is concerned with the occurrence and the functions of nouns referring
      to animals in the context of similes and metaphors implementing the metaphoric
      scheme "Human is an Animal". These phraseological units are the result of
      repressing the boundary percepts lying between a Human and a Non-Human. The data
      (5500 entries) is excerpted from English, German, Czech, and Russian
      phraseological lexicons and texts. The paper deals with the following:
      classification of animals appearing in the data; the classes are defined as the
      cross-section between zones of social distance, e.g. relatives, servants,
      strangers, etc., and zones of physical distance, e.g. house, farm, remote, etc.;
      establishing indices of popularity of animals; discussion of Sus srofa (the pig)
      in terms of its symbolic values in Germanic and Slavic cultures. The functional
      analysis of animal nouns and their referents is supported by quantitative
      statements.

PMID- 15156741
TI  - Body metaphors--reading the body in contemporary culture.
AB  - This paper addresses the linguistic reframing of the human body in contemporary
      culture. Our aim is to provide a linguistic description of the ways in which the
      body is represented in modern English language. First, we will try to focus on
      body metaphors in general. We have collected a sample of 300 words and phrases
      functioning as body metaphors in modern English language. Reading the symbolism
      of the body we are witnessing changes in the basic metaphorical structuring of
      the human body. The results show that new vocabulary binds different fields of
      knowledge associated with machines and human beings according to a shared textual
      frame: human as computer and computer as human metaphor. Humans are almost
      blended with computers and vice versa. This metaphorical use of the human body
      and its parts reveals not only currents of unconscious though but also the
      structures of modern society and culture.

PMID- 15156742
TI  - Semantic couplets as an expression of cultural identity.
AB  - Semantic couplets in the Nahuatl language can function as discourse markers that
      have the pragmatic function of building identities among speech communities. The
      subsistence of these linguistic structures in present day institutional
      discourses points to similarities, not only in social, religious but also in
      linguistic practices of speech communities that are distant in time. Semantic
      couplets are presented as evidence that links modern speech events with those
      from pre-Hispanic times.

PMID- 15156743
TI  - On German-Croatian and Italian-Croatian language contact.
AB  - Croatia has always been a multilingual environment. The influence of German and
      Italian was empowered through direct political influence. During the second part
      of the 18th and in the 19th century native speakers of German and Italian used
      Croatian as a second language carrying out their duties at work. This
      bilingualism can tentatively be referred to as bureaucratic bilingualism. Native
      Croatian speakers used Italian and German as a second language in certain social
      areas. Such bilingualism can tentatively be called civic bilingualism. It can be
      assumed that starting with the 1960s civic German and Italian bilingualism no
      longer existed. Language contact within the daily life results in German and
      Italian loan words in Croatian which are still actively present and used in daily
      communication.

PMID- 15156744
TI  - "Nature" and "environment" in German and Portuguese sustainable development
      strategies for Johannesburg 2002.
AB  - The recent Johannesburg Summit on Sustainable Development was an important
      symbolic moment, in spite of the poor results some people claim to have emerged
      from it. The very fact that official written texts were produced for a wide
      discussion in many participating countries is a positive side-effect, as it
      enables the almost unique possibility of using parallel corpora for the analysis
      of the respective language and underlying assumptions. This could lead to the
      identification of some potential causes for conflicts and misunderstandings. Both
      texts were produced according to a (supposedly, at least) common intention, so
      they may be seen as functionally equivalent. In spite of that, there are
      obviously huge differences, not only in extension, but also in the type of
      lexical combinations and stylistic features used. Words like ambiente, in the
      Portuguese language, and Umwelt, in German, as well as natureza/Natur, appear in
      very different lexical environments, so that one can, by means of a distributive
      methodology, obtain a picture of what might be intended with their use in the two
      countries. Another issue brought about by this analysis was a reflection on the
      concept of "foreign" language. This raises the question not only of knowing
      whether, or to what extent, written texts like these are really intended to have
      an effect on (local) people's minds, but also about pragmatic/cultural
      constraints that have influenced their very shaping.

PMID- 15156745
TI  - Traces of cannibalistic instinct in food denomination.
AB  - Drawing attention to the associations evoked in the process of food denomination,
      the paper attempts to reveal the traces of cannibalistic instinct in this realm.
      By singling out some of the principal ways used in the semantic reticulum to name
      food, special attention is devoted to those names that allude to particular
      categories of enemies (devoured as wholes or as parts of the body). What is
      referred to as "anti-taboo" shows how the linguistic and more generally the
      anthropological 'substitution process' is a human reaction to the persistence of
      the cannibalistic taboo in the face of the belief that cannibalism is an impulse
      far removed from modern society. Finally it is noted that cannibalistic metaphors
      have been analysed in other fields, whereas in the area of food denomination they
      have been neglected. The suggestion is that the reason for such neglect may lie
      in an attempt to conceal our closeness to the cannibalistic instinct in the form
      of linguistic substitution.

PMID- 15156746
TI  - Mayan master speakers--the archive of the indigenous languages of Chiapas.
AB  - The Archive of the Indigenous Languages of Chiapas is an electronic database
      documenting the three principal Indian languages of Chiapas, Mexico. This report
      describes the design philosophy behind the archive, intended to distribute its
      results in digital form via the Internet. It illustrates some of the products of
      the Archive, ranging from standard linguistic description and lexicography,
      through semi-experimental elicitation, to ethnographically situated interaction
      characterized by different sorts of speech genre. It also discusses
      presentational and ethical issues derived from electronic distribution of digital
      media in linguistic documentation.

PMID- 15156747
TI  - Language and cultural contacts among Yukatekan Mayans.
AB  - The Yukatekan branch of the Maya language family, spread across the Yucatan
      Peninsula of Mexico, northern Guatemala, and Belize, began to diversify
      approximately 1,000 years ago. Today it has four branches: Mopan Maya, Itzaj
      Maya, Lakantun Maya and Yukatek Maya proper, which have widely varying language
      statuses. Lakantun and Itzaj Maya are seriously threatened, while Mopan appears
      to have a stable or growing population of approximately 10,000 speakers and
      Yukatek has a very large number of speakers, perhaps 750,000. However, even many
      Yukateks believe that their language is threatened and that shift to Spanish is
      underway. During the past millennia there has been a series of contacts involving
      migration, trade, warfare, and flight among the different branches, as well as
      with other Mayan languages and with the Spanish. This paper examines a variety of
      different kinds of contact, and how the different language varieties were
      involved and affected. One goal of the paper is to better understand how the
      dynamics of inter-cultural contacts affects language practices resulting in very
      different language statuses and ideologies.

PMID- 15156748
TI  - The politics and semiotics of sounds--Mayan linguistics and nation-building in
      Guatemala.
AB  - This paper discusses the development Mayan linguistics as an authoritative field
      of knowledge in Guatemala. In particular, it links missionary linguists' and Maya
      linguists' activities with shifting nationalist agendas from the 1920s in to the
      late 1980s. It is argued that during the historical and intellectual moment that
      linguistics becomes an authoritative epistemology, phonetic analysis functions as
      a creative index that constitutes "expert" knowledge for particular semiotic and
      ideological reasons tied to competing versions of the Guatemalan imagined
      community.

PMID- 15156749
TI  - Language revitalization in Native North America--issues of intellectual property
      rights and intellectual sovereignty.
AB  - Language revitalization, oral tradition and epistemology are expressions of
      Native peoples intellectual sovereignty, and thus the foundation for indigenous
      intellectual property rights. As the people of California move towards language
      and cultural revitalization the question arises: What constitutes or constructs
      the definitions of intellectual property and how can appropriation of indigenous
      knowledge be protected? Looking at the issues faced by the California's
      indigenous populace and by implication, other indigenous peoples in the United
      States, this essay examines how protection may be afforded under the United
      Nations definition of 'heritage'. Given that the holding safe of a 'culture' or
      'heritage' is inclusive of language, and thus has been determined to be a human
      right.

PMID- 15156751
TI  - On the cultural unity of Europe and a European dictionary project.
AB  - There is a cultural unity of Europe, notwithstanding the Reformation. This unity
      must be 'consciously' recognized, in order to develop the concept of European
      togetherness. The paper will examine the common roots of the European vocabulary,
      submitting the project for the compilation of some dictionaries, to which
      European colleagues will be called to contribute. European languages must be
      studied no more as 'national' languages, but in the context of the European
      tradition, emphasizing what they have in common, and not what separates them.
      Hence the necessity of compiling dictionaries on a new basis, of which early,
      summary indications are given.

PMID- 15156750
TI  - Vitality and erosion of Molise Croatian dialect.
AB  - This paper gives a presentation of the condition of an endangered language
      located on the southern part of the Italian peninsula, spoken by a small
      community of transplanted Slavic population who fled the Eastern Adriatic coast
      during the Turkish invasion of the Balkan peninsula and have lived in complete
      isolation from related Slavic languages for five centuries surrounded by a
      majority of Italian speaking population. The overview of contact induced changes
      shows a high level of interferences at all structural levels resulting in a
      relatively stable mixed idiom. Preservation and revitalization efforts are
      discussed particularly in relation to the importance of writing and codification
      of the language as well as possible steps that can be undertaken in view of the
      link between language and the group cultural identity.

PMID- 15156753
TI  - Out-of-school-hours learning in the United Kingdom.
AB  - In the United Kingdom, out-of-school-hours learning (OSHL) is incorporated into
      education policy. This is the story of how demonstration projects, political
      lobbying, and funding combined with training, youth work, and schools to make
      such innovation mainstream "across the pond."

PMID- 15156752
TI  - Blurring the lines for learning: the role of out-of-school programs as
      complements to formal learning.
AB  - As debates continue over the effectiveness of after-school programs, we need to
      create stronger links between schools and out-of-school activities. Where do such
      connections begin? How can we integrate skill-building and academic competence
      into the out-of-school-time context?

PMID- 15156754
TI  - After-school as intermediary space: theory and typology of partnerships.
AB  - This chapter explores the nature of after-school partnerships and sets forth a
      theory and typology describing the way in which the intersection of partners
      creates a unique intermediary space.

PMID- 15156755
TI  - Processes of adjustment in organized out-of-school activities: opportunities and
      risks.
AB  - Participation in organized out-of-school activities leads to long-term
      psychosocial and educational benefits for young people. Now we're learning which
      features of these activities best support individual children.

PMID- 15156756
TI  - The critical ingredient: caring youth-staff relationships in after-school
      settings.
AB  - After-school settings are interpersonal in nature, and the quality of the
      relationships that are forged can directly influence youths' attendance decisions
      and the developmental benefits they derive. Programs should more effectively
      capitalize on this potential for caring adult-staff relationships.

PMID- 15156757
TI  - Medical intellectuals: resisting medical orientalism.
AB  - In this paper, we propose analogies between medical discourse and Edward Said's
      "Orientalism." Medical discourse, like Orientalism, tends to favor institutional
      interests and can be similarly dehumanizing in its reductionism, textual
      representations, and construction of its subjects. To resist Orientalism, Said
      recommends that critics--"intellectuals"--adopt the perspective of exile. We
      apply Said's paradigm of intellectual-as-exile to better understand the work of
      key physician-authors who cross personal and professional boundaries, who engage
      with patients in mutually therapeutic relationships, and who take on the public
      responsibility of representation and advocacy. We call these physician-authors
      "medical intellectuals" and encourage others to follow in their path.

PMID- 15156758
TI  - Survivor of that time, that place: clinical uses of violence survivors'
      narratives.
AB  - Narratives by survivors of abuse offer compelling entries into the experiences of
      abuse and its effects on health. Reading such stories can enlarge the clinician's
      understanding of the complexities of abuse. Furthermore, attention to narrative
      can enhance the therapeutic options for abuse victims not only in mental health
      arenas, but also in other medical contexts. In this article we define the genre
      of survivor narratives, examine one such narrative in particular (Push by
      Sapphire, 1996), and explore the clinical implications of narrative in abuse
      victims' clinical care.

PMID- 15156759
TI  - "Am I not a woman?" The rhetoric of breast cancer stories in African American
      women's popular periodicals.
AB  - Representations of breast cancer are examined in three popular women's
      periodicals targeting African American readers: Ebony, Essence, and Black
      Elegance. The researcher focuses specifically on representations that reflect
      certain ideas/ideals about the sharing and creating of information about the
      disease and related issues, such as health care and body image. Magazine
      selections are analyzed and critiqued according to the epistemological principles
      outlined by Patricia Hill Collins in Black Feminist Thought. The author calls for
      further research into how and why particular social and cultural groups consume
      information about health and illness in particular ways.

PMID- 15156760
TI  - [Occupational exposure to chemical carcinogens in Poland, 2001].
AB  - This paper discusses occupational exposure to chemical carcinogens in Poland in
      2001 based on data obtained from the Central Register of Carcinogen Agents
      (CRCA). The data on 3017 enterprises, in which employees were exposed to chemical
      carcinogens (chemicals, mixtures and technological processes involving
      carcinogenic agents) were collected by CRCA in 2001. More than 10,000 workers
      were exposed to crystalline silica. Diesel engine exhausts, formaldehyde and
      benzo[a]pyrene. The majority of exposed workers were in three southwestern
      regions (voivodships) of Poland: Slaskie, Doinoslaskie and Malopolskie.

PMID- 15156761
TI  - [Hygienic standards of the occupational air quality established by the Experts on
      Chemical Agents, 2002].
AB  - In 2002, it was necessary to harmonize Polish law on admissible limits of
      occupational exposure with EU requirements. To this end, the Expert Group on
      Chemical Agents proposed maximum admissible concentration values for 29
      chemicals: acrylaldehyde (107-02-8); cresols, mix of isomers (95-48-7), 108-39-4,
      106-44-5, 1319-77-3); tetraphosphorus decaoxide (1314-56-3); ethylamine (75-04
      7); naphtalene (91-20-3); nitrobenzene (98-95-3); nitrogen oxide (110-54-5);
      nitrogen dioxide (10102-44-0); pyridine (110-86-1); butan-2-one (78-93-3); carbon
      oxide (630-08-0); 1,4-dichlorobenzene (106-46-7); 1,2-dichlorobenzene (95-50-1);
      hexane (110-54-5); aluminum hydroxide (21645-51-2); aluminum (fumes and dusts)
      (7429-90-5); amitrole (61-82-5); 2,2-bis(4-hydroxyphenyl)propane (bisphenol A)
      (80-05-7); 3a,4,7,7a-terahydro-4,7-metanoindene (dicyclopentadiene) (77-73-6);
      trimethoxyphosphane (121-45-9); methyl chloroacetate (96-34-4); 4-methoxyphenol
      (150-76-5); methyl formate (107-31-3); 2-phenoxyethanol (122-99-6);
      divinylbenzene (1321-74-0); Diesel exhausts (-); hexane-6-lactam (dusts and
      fumes) (105-60-2); 2-isopropoxyethanol (109-59-1); and methyl 2-cyanoacrylate
      (137-05-3).

PMID- 15156762
TI  - [Biological monitoring of chemical exposure].
AB  - The concept of biological monitoring (BM) has evoked a lot of interest among
      individual scientists and international organizations. Biological monitoring of
      exposure has thus far been applied to environmental and occupational toxicology
      or epidemiological studies. At present, BM plays no more than complementary role
      in industrial hygiene. Moreover, it is not clear whether BM belongs to
      occupational hygiene or to occupational medicine. Consequently, BM
      recommendations are not regarded as legal standards in most countries. Nowadays,
      when analytical problems have almost ceased to exist due to new laboratory
      techniques and quality assurance systems, the methods for interpreting the
      results have become a major issue. New, promising areas of BM application include
      determination of pesticides, antineoplastic drugs, hard metals, and unchanged
      volatile organic compounds in urine. The identification of new possible health
      based biomarkers of exposure and the development of more sensitive methods due to
      decreasing occupational exposure limits seem to be one of the most important
      issues.

PMID- 15156763
TI  - [Methods of assuring research quality in industrial hygiene laboratories].
AB  - Quality assurance is a part of quality management to ensure that the requirements
      of good quality are met. Quality assurance can be considered from two aspects,
      laboratory organization and management and technical activity, e.g. testing,
      analytical techniques or analytical equipment. Quality of testing in industrial
      hygiene laboratories can be achieved using appropriate methods of quality control
      of sampling and analytical processes. These methods should be well planned and
      properly documented, while statistical techniques should be used to verify the
      results. The outcome of quality control plans aimed at improving the quality of
      tests can contribute to the improvement of analytical proficiency, assuring
      quality, validation or revalidation of methods and estimation of measurement
      uncertainty.

PMID- 15156764
TI  - [Good laboratory practice in occupational hygiene].
AB  - Good laboratory practice (GLP) is the system that ensures quality assessment,
      defines the organization rules of institutions performing non-clinical studies in
      the area of human and environmental safety in general, and of chemicals and
      chemical preparations in particular as well as sets the conditions of planning,
      performing and monitoring of studies, the outcome of which is recorded, stored
      and reported. Occupational hygiene is an area of activities that involves
      anticipation, assessment and surveillance of health hazards in the work
      environment aimed at protecting health of workers and the population at large
      (IOHA). Assessment and control of harmful agents, which occur in the work
      environment, technological processes or methods of work should be carried out by
      research units (laboratories) with well documented competencies in the
      environment and/or biological monitoring, and those granted accreditation
      according to EN/ISO 17025. Anticipated risks should be based on analyses of
      physical, chemical and toxic properties of harmful agents, performed in line with
      the rules of good laboratory practice. Accredited laboratories and the quality of
      their tests are monitored by governmental agencies. The application of the GLP
      system provides: the opportunity to investigate analytical procedures and data
      (the documentation concerning each stage of a given analysis should ensure a
      complete reconstruction of the whole analytical process); the confirmed
      reliability of the results; the recognition of the results in European Union
      member states and by the Organization for Economic Cooperation and Development
      (OECD); the opportunity to avoid repetition of analyses and studies; a better
      care of the human health and environment.

PMID- 15156765
TI  - [Occupational bio hazards: current issues].
AB  - Over the last decade, there was noted a large advancement of knowledge on living
      organisms and their products posing a potential occupational risk. Novel risk
      factors, often new to science, were identified, the role and significance of
      already known factors better comprehended, and occupational groups endangered by
      biological hazards more thoroughly recognized. Novel viruses and prions, emerging
      in different parts of the world, may pose a particular threat to health and life
      of health care workers, agriculture workers and veterinarians. A new coronavirus
      (SCoV) that evoked a rapid outbreak of disease described as severe acute
      respiratory syndrome (SARS) in the first half of 2003 may serve as an example.
      The disease was particularly common among health care workers. Previously
      discovered zoonotic viruses, Nipah virus in pigs and Hendra virus in horses, may
      be a cause of fatal encephalitis in animal farmers. Hantaviruses (Puumala,
      Hantaan, Sin Nombre and others) infecting field rodents may be a cause of
      hemorrhagic fever with renal syndrome (HFRS) or pulmonary syndrome (HPS) in
      farmers and laboratory workers. Prions responsible for inducing a zoonotic
      variant of Creutzfeldt-Jakob disease (vCJD) are considered to be a potential
      cause of work-related infections in agricultural and health care workers,
      however, this assumption has not as yet been supported by any conclusive
      evidence. In many countries, blood-borne occupational infections with hepatitis C
      virus (HCV) is the major epidemiological problem among health care workers,
      mostly because no vaccine against this virus has been produced to date.
      Vaccinations effectively restricted the number of occupational infections with
      hepatitis B virus (HBV), and work-related infections with human immunodeficiency
      virus (HIV) causing acquired immunodeficiency syndrome (AIDS) are very rare.
      Hazardous bioserosols, occurring in many work environments, pose an occupational
      health hazard of particular importance. Many new biological factors present in
      organic dusts that may induce work-related allergic and immunotoxic diseases
      among farmers and workers of the agricultural and wood industries have been
      identified. Droplet aerosols, which are generated from water, oils, oil-water
      emulsions and other liquids in various work environments, may contain infectious
      agents (Legionella spp.) as well as allergic and/or toxic agents. It has been
      shown that allergens and endotoxins produced by Gram-negative bacteria occurring
      in oil mist from metalworking fluids may cause occupational respiratory diseases
      in workers of the metallurgic industry.

PMID- 15156766
TI  - [Allergy in the workplace--epidemiological prognoses and perspectives of hygienic
      prophylaxis].
AB  - Asthma and allergy are common among adults of the working age and their
      prevalence is growing in developed countries. The implementation of an effective
      surveillance, "sentinel" program, like the British SWORD is required so that
      public health strategies can be developed for occupational asthma and allergy in
      Poland. The use of personal dust samplers and specific immunoassays has
      facilitated the evaluations of exposure response relationships in workers exposed
      to high molecular weight sensitizers, e.g., wheat allergens, fungal alpha
      amylase, laboratory animal allergens. To introduce hygiene standards for
      occupational allergens their standardization is still required, let us hope that
      this tasks will be very soon accomplished.

PMID- 15156767
TI  - [The examination of induced sputum in diagnosis of pulmonary diseases, in
      general, and in occupational asthma, in particular].
AB  - Occupational bronchial asthma is one of the most frequent occupational lung
      diseases in many countries throughout the world. The diagnosis of this disease is
      based on clinical and occupational histories, positive immunological tests with
      potentially allergic agents and functional respiratory tests. However, over the
      recent years, the induced sputum method has become a new test with promising
      results for the study of occupational airway diseases. The current state of
      knowledge of the role of induced sputum in occupational asthma and other
      respiratory diseases is presented in this article.

PMID- 15156768
TI  - [Hygienic assessment of sources of electromagnetic fields using revised and new
      standards of maximum admissible intensities].
AB  - In 2001, the legal regulation on maximum admissible intensities (MAI) of
      electromagnetic fields (EMF) in the frequency range of 0-300 GHz was amended. In
      the existing regulation, the ranges for frequencies between 0 and 50 Hz and
      between 50 Hz and 1 kHz were not defined, and for the frequency of 50 Hz there
      were no regulations for the electric component. The amended regulation expands
      the obligation to measure and assess the magnetic component up to 3 GHz (formerly
      to 10 MHz only) and moderates the admissible level for extremities at the
      frequency below 800 kHz (magnetic component). In addition, the MAI values are
      thoroughly verified in the whole range of standardized frequencies. Formally, all
      kinds of power supplied equipment are the source of EMF. In practice, the
      measurement of all equipment and installations is not feasible or justified.
      According to the Database by the Chief Sanitary Inspector, the number of EMF
      sources recorded by the sanitary inspection in 2002 exceeded 60 thousand.
      Therefore, it was found advisable to analyze the results obtained from the
      studies of occupational exposure to EMF after the introduction of new MAI'2001 to
      select equipment and to find out whether equipment and installations generating
      EMF corresponding at most with protective zone needs to be controlled. The
      analysis covered 9 thousand of equipment and installations of various types (data
      collected by the Central Database on EMF sources and our own data), in particular
      EMF sources: strong EMF with endangered protective zone and non-identified levels
      of generated EMF; weak EMF but responsible for chronic exposure; and EMF sources
      occurring in large quantities in places where people work or have to stay longer
      (e.g., hospitals, treatment rooms, production halls). The analysis facilitated
      the hygienic evaluation of the equipment and installations according to MAI'2001.
      In all, 49% of equipment were found not to be the source of EMF with values from
      protective zones, and thus it is obvious that their control is not justified as
      exposure does not occur or in case of occupational exposure it can be neglected.
      The authors present a long list of equipment and installations with the maximum
      levels of generated EMF. The level of generated EMF was assessed according to the
      criterion of protective zones: intermediate, hazardous and dangerous.

PMID- 15156769
TI  - [The effect of low frequency noise on human mental performance].
AB  - There is a growing body of data showing that low frequency noise (LFN) defined as
      broadband noise with dominant content of low frequencies (10-250 Hz) differs in
      its nature from other noises at comparable levels. The aim of this study was to
      assess the influence of LFN on human mental performance. Subjects were 193 male
      paid volunteers. They performed standardized tests: the Signal Detection Test
      (test I), the Stroop Color-Word Test (test II), and two sub-tests of the General
      Aptitude Test Battery, i.e. the Math Reasoning Test (test III) and the Comparing
      of Names Test (test IV). Three different acoustic conditions were used in the
      experiment the background laboratory noise of about 30 dB(A), LFN and the
      broadband noise at comparable db(A) levels of 50 dB. The study subjects were
      assigned randomly to varied experimental conditions. After the test session, the
      subjects completed a questionnaire aimed at rating the subjective annoyance of
      exposure conditions during the tasks, and assessing individual sensitivity to
      noise in general and LFN in particular. The main effects of exposure and/or noise
      sensitivity on the tests' results or their interaction were found in three of the
      four tests performed (tests I, II and IV). The tendency towards weaker results in
      low frequency noise compared to other conditions was observed in persons
      classified in test II as more sensitive to LFN (higher value of reading
      interference). The significant effect of both exposure and sensitivity to noise
      on annoyance rating during test performance was also noted. The annoyance of LFN
      and reference noise was rated higher than that of background noise. LFN at 50
      dB(A) could be perceived as annoying and adversely affecting mental performance
      (concentration and visual perception), particularly in persons sensitive to LFN.

PMID- 15156770
TI  - [Individual protection devices--opinion and practice of occupational medicine
      physician].
AB  - Technological developments have led to changes in work conditions and the
      character of work itself that modify the responsibilities and tasks of
      occupational medicine physicians. Their major task is to protect workers' health
      through primary prevention, which means the employment of all available measures
      to prevent adverse health effects resulting from working conditions unfavorable
      to human health. Statistical data on the incidence of occupational diseases and
      accidents at work in Poland show that despite many beneficial changes, better
      labor organization or new technologies in production and services, social and
      economic consequences of exposure-related diseases induced by so called hard
      harmful agents in the work environments are still the major problem, hence the
      significance of prevention. Activities aimed at preventing hazards at workplace
      should be carried out by employers, safety and work hygiene services and
      physicians involved in prophylactics. In addition, the selection and supply of
      individual protectors as well as their use by workers to protect themselves
      against dangerous and harmful factors occurring in the work environment play an
      essential role. The authors discuss the significance of using individual
      protectors from the viewpoint of occupational medicine physicians, and the tasks
      of this group of physicians in the light of epidemiology of occupational diseases
      induced by various agents present in the work environment.

PMID- 15156772
TI  - [Comparison between calculation- and measurement-based assessments of the effects
      of ambient air dust concentration on the environment and health status of the
      population living in the vicinity of a mineral mining plant].
AB  - Airborne and PM10 fraction dust concentrations were measured at seven measurement
      points in the area occupied by the plant. A GRIMM 1.105 laser meter was used to
      determine automatically total dust and PM10 fraction concentrations at 1 min
      intervals. The measurements were continued for 1 to 3 days at selected
      measurement points. The results were used to calculate the 30-min and mean 24-h
      (C24) concentrations. Significant differences were found to exist in the
      assessment based on the calculated and measured results of the ambient air dust
      concentrations. The calculation-based assessment did not predict any values above
      admissible limits, while the measurement-based assessment resulted in dust
      concentration values dangerous to the exposed population living in the vicinity
      of the plant, over both short (days) and long (years) time intervals. In
      emergency situation, when the dust-collection system was inoperative, dust
      concentrations in the ambient atmosphere of the plant were even 100 times higher
      than the current admissible values.

PMID- 15156771
TI  - [Responsibilities of enterprises introducing new dangerous chemical substances
      and preparations].
AB  - The paper reviews the responsibilities of producers, importers and distributors
      set in a new Act of January 2001 on chemical substances and preparations (Off. J.
      2001, No. 11, item 84, with subsequent amendments). This Act together with
      executive provisions is aimed at harmonizing Polish legislation with EU
      requirements. The Act sets conditions, restriction and bans of production placing
      on the market and use of chemical substances and preparations in order to protect
      human health and environment against their harmful effects. The Act together with
      a number of executive provisions render those who introduce dangerous chemicals
      and chemical preparations, including distributors responsible for: classification
      and labelling of dangerous chemical substances and preparations; possessing,
      making available and up-dating safety data sheets; supplying packages containing
      certain dangerous substances with child-proof fastenings; notifying the Inspector
      for Chemical Substances and Preparations about placing a dangerous preparation on
      the market; notifying the Inspector about a new substance and conducting required
      studies; being properly qualified to handle dangerous substances. The Act
      strictly defines the term "placing a substance or a preparation on the market"-
      it means making a substance or a preparation available to third parties on the
      territory of The Republic of Poland, territories of the Member States of the
      European Union or the territory of Iceland, Liechtenstein and Norway, unless the
      Act provides otherwise; it also means introduction of a substance or a
      preparation from outside of the territory referred to above on the customs
      territory of The Republic of Poland, or that of the member states of the European
      Union and other states listed above. In addition, some of the responsibilities
      defined by the provisions of the law on chemical substances and preparations are
      also applicable to handling of biocidals, which are classified as dangerous
      substances. The Act also defines the terms "substance" and "chemical preparation"
      and sets the rules for classification and labelling of dangerous chemical
      substances and preparations (criteria for classification, rules for labelling,
      introduces the official classification and labelling of certain substances in the
      "list of dangerous substances"). The Act identifies methods to be used in the
      tests of physico-chemical properties, toxicity and ecotoxicity of chemical
      substances and preparations to meet the legal requirements and sets criteria to
      be followed by institutions involved in such testing.

PMID- 15156773
TI  - [Teratogenic effect of rubber components].
AB  - This study was performed to evaluate the effects of prenatal development of rats
      were exposed to Polnoks R and its monomer 2,2,4-trimethyl-1,2-dihydroquinoline
      (TMDHQ) by gavage every day on days 6-15 of gestation at doses equivalent 6%, 13%
      and 25% of LD50. Polnoks R and TMDHQ administered per os associated with
      significant maternal toxicity, embryonal lethality, retarded fetal development
      and congenital defects. Polnoks R induced skeletal malformations, internal
      hydrocephalus, and hydronephrosis. 2,2,4-trimethyl-1,2-dihydroquinoline produced
      internal malformations (exencephale, hydrocephalus, anophthalmia, hydronephrosis
      and renal hypoplasia) and skeletal malformations of ribs and vertebrae. Polnoks R
      monomer--2,2,4-trimethyl-1,2-dihydroquinoline is used as an antioxidant in
      elastomer and rubber productions. Polnoks R and its monomer 2,2,4-trimethyl-1,2
      dihydroquinoline are teratogenic to rats and induces CNS, kidneys and skeletal
      defects.

PMID- 15156774
TI  - [Integrated prophylactic care of employees--is it a future model?].
AB  - The author presents his own experience in the area of prophylaxis and cooperation
      with safety and health services as well as with occupational hygienists. The
      attention is turned to an essential difference between two terms "employees" and
      "workers". The proposed model of integrated prophylactic care is described and
      the need for cooperation between Trade Unions, National Insurance Company (ZUS)
      and Agricultural Insurance Company (KRUS) is highlighted. In the author's opinion
      the integrated occupational health services, safety and health services and
      occupational hygiene should be a future model of workers' health protection in
      Poland. Integrated units should cover with their activities all employees
      throughout the country.

PMID- 15156775
TI  - Functional assessment for persons with musculoskeletal pain and impairment.

PMID- 15156776
TI  - Measurement properties of performance-based assessment of functional capacity.
AB  - Performance-based functional assessments, including standardized functional
      capacity evaluation (FCE) batteries, are commonly used to determine the physical
      work abilities of individuals who have sustained musculoskeletal injury. The
      purpose of this paper is to critically examine research pertaining to the
      measurement properties of performance-based FCE, along with the theoretical bases
      for such measurement. While rater judgments of maximum performance during FCE
      appear reliable, FCEs do not appear to be purely tests of physical capacity as
      performance during assessment is influenced by multiple personal and
      environmental contextual factors. FCEs are more accurately considered behavioural
      tests influenced by multiple factors including physical ability, beliefs, and
      perceptions, and should be interpreted with in the subject's broader personal and
      environmental context.

PMID- 15156778
TI  - Psychosocial factors that can influence the self-assessment of function.
AB  - What has plagued the evaluation process in this area has been the level of
      agreement in the wide variation in the measures used to document a construct such
      as pain, as well as changes in that construct as reflected in the measurement of
      function. The present article reviews the major psychosocial barriers to
      assessment/recovery that have been implicated as influencing the self-assessment
      of function. The following are discussed: secondary gain; secondary loss;
      emotional distress (such as anger, anxiety and depression); psychopathology;
      somatization and symptom magnification; compliance and resistance; patient
      comprehension/mental status; and iatrogenic effects.

PMID- 15156779
TI  - Generating workplace accommodations: lessons learned from the integrated case
      management study.
AB  - Modified duty and other accommodations by employers have been shown to be helpful
      in managing workplace disability associated with injuries and illnesses. Benefits
      of accommodation have been attributed to both reduced physical and psychosocial
      exposures. Although many employers have adopted proactive return to work policies
      that emphasize temporary work modifications, standardized methods for specifying
      appropriate accommodations have been elusive. On the basis of the experiences and
      results of a randomized controlled study of case management services for work
      related upper extremity disorders, we describe issues pertaining to the
      application of self-report measures of function and exposure assessment for
      generating accommodations. Challenges of this approach are 1) including specific
      work tasks on measures of physical function; 2) improving concordance between
      ergonomic exposure categories and methods of accommodation; and 3) providing a
      structured process for negotiating employee and employer preferences. To improve
      the effectiveness and efficiency of accommodation efforts, new tools for
      assessing function and ergonomic exposures in the workplace should be developed
      to specify accommodations more directly.

PMID- 15156777
TI  - History, design characteristics, and uses of the pictorial activity and task
      sorts.
AB  - Development of the Pictorial Activity and Task Sort (PATS) technology in the
      field of Occupational Rehabilitation is described. The history of several PATS
      measures is traced, and each measure is briefly described. The use of these
      measures to efficiently collect data in functional capacity evaluation and to
      provide guidance in occupational rehabilitation is briefly described. Key design
      characteristics are presented and several recommendations are provided for future
      development of PATS.

PMID- 15156780
TI  - Practical aspects of functional capacity evaluations.
AB  - Physicians, employers, insurers, and benefits adjudicators often rely upon
      functional capacity evaluations (FCEs) to determine musculoskeletal capacity to
      perform physical work, often with legal or occupational consequences. Despite
      their widespread application for several decades, a number of scientific, legal,
      and practical concerns persist. FCEs are based upon a theoretical model of
      comparing job demands to worker capabilities. Validity of FCE results is optimal
      with accurate job simulation and detailed, intensive assessments of specific work
      activities. When test criteria are unrelated to job performance, or subjective
      evaluation criteria are employed, the validity of results is questionable.
      Reliability within a subject over time may be adequate to support the use of
      serial FCE data collection to measure progress in worker rehabilitation.
      Evaluation of sincerity of effort, ability to perform complex or variable jobs,
      and prediction of injury based upon FCE data is problematic. More research,
      especially studies linking FCE results to occupational outcomes, is needed to
      better define the appropriate role for these evaluations in clinical and
      administrative settings.

PMID- 15156781
TI  - A Festschrift for Edoardo Bisiach (and spatial neglect).

PMID- 15156782
TI  - Visual neglect can be object-based or scene-based depending on task
      representation.
AB  - Three patients with visual neglect were tested on their ability to detect target
      letters at ipsilesional and contralesional locations on a monitor, and at
      different locations within large shapes on the monitor. When patients were asked
      to detect targets within the entire monitor, they showed neglect for all the
      contralesional hemifield. In contrast when they were asked to detect targets
      within a particular object, they showed object-based neglect. In these two
      conditions the displays, the targets and the response were identical, with the
      only difference being the space that is represented for the task. These results
      show that the reference frame of visual neglect may be altered by task
      instructions changing how a structured visual scene is represented, with neglect
      applying to the contralesional side of this represented space.

PMID- 15156783
TI  - Hemispatial neglect and visual search: a large scale analysis.
AB  - Visual search tasks have standardly been divided into two categories: those in
      which the target is detected through a serial, attention-driven search and those
      in which the target is detected rapidly in parallel and, apparently, without
      attentional processing. Several studies have examined this distinction in
      patients with hemispatial neglect with the clear prediction that the former, but
      not the latter, should be impaired. These studies, however, have proved
      inconclusive. We have addressed this issue in a large sample of patients with
      unilateral hemispheric infarcts to the left or right hemisphere. In addition to
      measuring the patients' performance on both types of visual search tasks, we
      documented the presence and severity of neglect and of visual field defects in
      these same individuals. Patients with brain-damage with or without accompanying
      neglect were impaired at searching for the contralateral target on both forms of
      visual search, relative to normal control subjects, although this deficit was
      magnified in individuals with neglect and was also exacerbated by the presence of
      hemianopia. This pattern was also more pronounced in individuals with right-than
      with left-hemisphere lesions. The findings not only clarify the contradictory
      neuropsychological data but also provide clear evidence for the involvement of
      attentional processing in all forms of visual search.

PMID- 15156784
TI  - Hermann Zingerle's "Impaired perception of the own body due to organic brain
      disorders". 1913. An introductory comment, and an abridged translation.
AB  - In the late 1970's Edoardo Bisiach and his coworkers provided definitive evidence
      that spatial unilateral neglect involves a disorder of the internal
      representation of extra-personal space. A few years later Bisiach and Berti
      (1987) revived the so far neglected contribution of an Austrian neurologist,
      Hermann Zingerle (1913). Ninety years ago Zingerle had described the symptom
      complex of two right-brain-damaged patients, who showed left hemisomatoagnosia,
      unawareness of left hemiplegia, and left motor neglect. In addition to the
      detailed case reports, Zingerle had put forward a unitary interpretation of these
      deficits in terms of a disordered representation of one side of the body
      (dyschiria). A unitary representational account of these unilateral impairments
      was conspicuously absent in the contemporary neurological literature (Anton,
      Pick, Babinski), and attracted Bisiach's interest. An abridged translation of
      Zingerle's paper is provided. The clinical case reports and Zingerle's
      conclusions are discussed, with reference both to Bisiach's views, and to present
      knowledge of unilateral spatial neglect.

PMID- 15156785
TI  - Cognition in dyschiria: Edoardo Bisiach's theory of spatial disorders and
      consciousness.
AB  - An overview of Bisiach's theory of mental representations and consciousness is
      presented. Neuropsychological observations on space disorders led Bisiach to
      consider analogical representations (and not only symbolic representations) as
      truly 'cognitive', insofar as they are necessary for the normal functioning of
      linguistic processes. Bisiach's approach to the scientific study of
      consciousness, conceived both as the private aspect of phenomenal experience and
      as a monitoring process, is also discussed.

PMID- 15156786
TI  - The role of vision in spatial representation.
AB  - A complex link exists between vision and unilateral spatial neglect (USN).
      Firstly, USN is not a perceptual deficit, secondly, USN is not necessarily
      accompanied by a visual deficit and finally, USN can be observed in non-visual
      modalities as well as in mental spatial imagery. This apparent supramodality of
      USN stands in sharp contrast to the fact that neglect signs are often more severe
      and more durable in the visual than in other sensory modalities (Chokron et al.,
      2002). The influence of vision on spatial representation has rarely been studied.
      In the present study we assessed six right brain-damaged patients suffering from
      left USN on two tasks involving spatial representations: a clock-drawing task and
      a drawing from memory task in two experimental conditions, with and without
      visual control. We confirm that even in mental imagery, the absence of visual
      feedback may decrease and even suppress left neglect signs (Bartolomeo and
      Chokron, 2001b; 2002). Since vision is largely involved in the orientation of
      attention in space, suppressing visual control could reduce the magnetic
      attraction towards the right ipsilesional hemispace and in this way could allow a
      re-orientation of attention towards the left neglected hemispace. We discuss the
      theoretical and therapeutic implications of these findings.

PMID- 15156787
TI  - Auditory neglect: what and where in auditory space.
AB  - A sound that we hear in a natural setting allows us to identify the sound source
      and to localise it in space. Several lines of evidence indicate that the two
      aspects are processed in anatomically distinct cortical networks. Auditory areas
      that are part of the What or Where processing streams have been identified
      recently in man and in non-human primates. Comparison between anatomical and
      activation studies suggests that processing within either stream can be modulated
      by specific attentional factors. Attending to auditory events can be affected in
      neglect. Bisiach et al. (1984) described systematic directional errors to the
      ipsilesional space, which was considered a manifestation of hemispatial neglect
      and interpreted as a disruption of the neural network providing the internal
      representation of egocentric space. The other manifestation of auditory neglect
      is contralesional extinction in dichotic listening condition (Heilman and
      Valenstein, 1972). Recently two types of auditory neglect have been described,
      one corresponding to a primarily attentional deficit associated with basal
      ganglia lesions and the other to distortions of auditory space representations
      associated with parieto-prefrontal lesions (Bellmann et al., 2001). Based on
      studies of sound detection and sound recognition following hemispheric lesions we
      argue that the two types of neglect correspond to disturbed processing in either
      the What or the Where stream.

PMID- 15156788
TI  - Developmental neglect dyslexia in a Hebrew-reading child.
AB  - This paper describes for the first time a detailed study of a child with neglect
      dyslexia. NT is 10-year-old child, with left word-based neglect dyslexia, without
      clinical signs of visuo-spatial neglect. Since he is a native speaker of Hebrew,
      which is read from right to left, his neglect dyslexia manifests in omissions and
      substitutions of final letters. He is severely impaired in single words, with 96%
      of his errors being omissions and substitutions of final letters. When presented
      with more than one word, in word pairs, sentences or text, he neglects the left
      part of each word, but never omit whole words on the left side of the page. His
      reading improves considerably when the same word is presented vertically or when
      manipulations are done to shift his attention to the left--with coloured final
      letters, flashing light, or tapping his finger to the left of each word. NT's
      neglect dyslexia is very selective, with good reading of numbers and symbols, and
      even good performance on letter sequences when no reading is required. A
      dissociation is also detected between his impaired reading due to neglect
      dyslexia and his normal performance on conventional clinical tests of general
      visual neglect visual of line, object and letter cancellation, line bisection,
      object drawing and copying. His neglect dyslexia seems to be developmental as no
      abrupt onset is reported.

PMID- 15156789
TI  - Acceleration perception and spatial distortion in a left unilateral neglect
      patient.
AB  - To explain relative leftward overextension in a line extension task by left
      unilateral neglect subjects, Bisiach et al. (1998) suggested that the
      representation of space is distorted--i.e., dilated towards the left side. If
      perception of the velocity of a moving stimulus is due to a calculation of the
      distance covered per unit time in representational space, then a stimulus with
      uniform linear motion should be perceived as decelerating when moving leftwards
      in the visual field of a subject with left unilateral neglect. We investigated
      the perception of acceleration in a patient with left unilateral neglect and
      spatial distortion (revealed as relative left overextension in a line extension
      task) using a task in which the stimuli were right and left moving targets with
      variable acceleration. The patient's ability to perceive acceleration was much
      lower (higher acceleration threshold) for leftward movements than rightward
      movements. Fourteen months later unilateral neglect had improved, and the
      relative left overextension and decreasing acceleration threshold for leftward
      movements were reduced. By contrast, alterations in the perception of
      acceleration for leftward movements were not found in a patient with left
      unilateral neglect and left underextension and in a patient with right brain
      damage and left hemianopia. These findings in one patient with left spatial
      unilateral neglect and a relative left overextension in a line extension task are
      consistent with the hypothesis that representational space is distorted, with a
      disproportionate leftward expansion, that affects perception of movement.

PMID- 15156790
TI  - Perceptual and premotor neglect: is there an ideal task to categorise patients?
AB  - This review focuses on Edoardo Bisiach's particular input into the
      perceptual/premotor taxonomy within the neglect syndrome and assesses arguments
      and experimental designs that have been presented both for and against the
      dichotomy. Bisiach made most crucial contributions to this topic as well as
      increasing insights into the syndrome of hemispatial neglect more generally. Most
      importantly, he elucidated its relevance to visual neuropsychological and
      neuroscientific research.

PMID- 15156792
TI  - "Mind the gap": the size-distance dissociation in visual neglect is a cueing
      effect.
AB  - There is a growing body of evidence that the processes mediating the allocation
      of spatial attention within objects may be separable from those governing
      attentional distribution between objects. In the neglect literature, a related
      proposal has been made regarding the perception of (within-object) sizes and
      (between-object) distances. This proposal follows observations that, in size
      matching and bisection tasks, neglect is more strongly expressed when patients
      are required to attend to the sizes of discrete objects than to the (unfilled)
      distances between objects. These findings are consistent with a partial
      dissociation between size and distance processing, but a simpler alternative must
      also be considered. Whilst a neglect patient may fail to explore the full extent
      of a solid stimulus, the estimation of an unfilled distance requires that both
      endpoints be inspected before the task can be attempted at all. The attentional
      cueing implicit in distance estimation tasks might thus account for their
      superior performance by neglect patients. We report two bisection studies that
      address this issue. The first confirmed, amongst patients with left visual
      neglect, a reliable reduction of rightward error for unfilled "gap" stimuli as
      compared with solid lines. The second study assessed the cause of this reduction,
      deconfounding the effects of stimulus type (lines vs. gaps) and attentional
      cueing, by applying an explicit cueing manipulation to line and gap bisection
      tasks. Under these matched cueing conditions, all patients performed similarly on
      line and gap bisection tasks, suggesting that the reduction of neglect typically
      observed for gap stimuli may be attributable entirely to cueing effects. We found
      no evidence that a spatial extent, once fully attended, is judged any differently
      according to whether it is filled or unfilled.

PMID- 15156791
TI  - Judging the angles formed by visible and imaginary clock hands: a study of
      hemispatial effects in healthy volunteers.
AB  - Healthy, right-handed volunteers (six male, six female) either saw or imagined
      the hands of a clock set a particular time. In both conditions, they then judged
      whether the angle between the clock hands was greater than or less than 90
      degrees. Subjects pressed one of two response keys to indicate their decision,
      and hand of response (left/right) was counterbalanced within and between
      subjects. The subjects had significantly longer reaction times and made
      significantly more errors when the imaginary angles formed by the clock hands
      were located in left hemispace (e.g. 8:30) than right hemispace (e.g. 4:30). With
      visible hands, there was no reaction time difference between visual hemifields,
      although significantly more errors were made when the angle formed by the hands
      fell within the left visual field. In the perceptual task (visible hands),
      reaction times and error rates increased monotonically as the distance between
      the hands approximated more closely to 90 degrees. This psychophysical
      relationship was not found in the representational task (imaginary hands).
      Rather, there was a significant positive correlation between reaction times/error
      rates and the magnitude of the number indicative of the position of the minute
      hand. The latter finding is consistent with the hypothesis that the lateral
      asymmetry in the representational task (reaction times and error rates are higher
      in left hemispace) is due to the time taken to mentally rotate the imaginary
      minute hand in a clockwise direction. No such operation is required in the
      perceptual condition where the hands are clearly visible.

PMID- 15156793
TI  - Auditory deficits in visuospatial neglect patients.
AB  - Since the pioneering experimental work of Bisiach et al. (1984) on deficits in
      sound localisation associated with unilateral brain lesions and visual neglect, a
      number of systematic investigations have examined auditory processing in
      visuospatial neglect patients. Evidence from a variety of experimental paradigms
      has revealed some auditory deficits in detection and identification tasks, during
      bilateral stimulation; plus localisation deficits for single sounds. These
      deficits emerge predominantly for contra-lesional sounds, although some auditory
      disturbances applying to both contra- and ipsilesional sounds have also been
      documented. Here we review evidence suggesting that some of these auditory
      deficits arise in relatively high-level stages of spatial processing. In
      addition, we present new analyses showing that auditory deficits in
      identification and localisation tasks often correlate with clinical measures of
      visual neglect, across a variety of different studies and tasks. This empirical
      relation suggests that a disturbance of multisensory spatial processing may often
      account for the joint auditory and visual spatial deficits in neglect patients,
      although rarer dissociations between the modalities should also be considered.

PMID- 15156794
TI  - The anatomy of anosognosia for hemiplegia: a meta-analysis.
AB  - Anosognosia for hemiplegia is the denial of the contralesional motor deficits
      that may follow brain damage. Although this disturbance has been reported in the
      neurological literature since the beginning of the last century, only few
      longitudinal studies have addressed the issue of the anatomical substrate of the
      disorder. Here we present a comprehensive review of the literature on anosognosia
      for hemiplegia from 1938 to 2001, taking into account some of its clinical,
      epidemiological and anatomical aspects. In particular, an attempt has been made
      to identify the intra-hemispheric lesion locations most frequently associated to
      the denial behaviour. Our review shows that anosognosia for hemiplegia most
      frequently occurs in association to unilateral right-sided or bilateral lesions
      of different brain areas (cortical and/or subcortical). It seems to be equally
      frequent when the damage is confined to frontal, parietal or temporal cortical
      structures, and may also emerge as a consequence of subcortical lesions.
      Interestingly, the probability of occurrence of anosognosia is highest when the
      lesion involves parietal and frontal structures in combination, if compared to
      other combinations of lesioned areas. This pattern of lesions suggests the
      existence of a complex cortico-subcortical circuit underlying awareness of motor
      acts that, if damaged, can give raise to the anosognosic symptoms.

PMID- 15156795
TI  - Impaired working memory for location but not for colour or shape in visual
      neglect: a comparison of parietal and non-parietal lesions.
AB  - Patients with spatial neglect due to right hemisphere pathology may show
      'revisiting' behaviour during visual search and cancellation tasks, such that
      previously encountered targets are treated as if they are new discoveries.
      Revisiting behaviour is particularly evident when no visible trace is left to
      inform patients that a particular target has already been detected (Husain et
      al., 2001; Wojciulik et al., 2001), implying that spatial working memory may be
      impaired in neglect. To test whether working memory for location is selectively
      impaired relative to memory for colour and shape, we compared performances of
      right hemisphere neglect patients with parietal (n = 4) and non-parietal (n = 4)
      lesions on a change detection task. Patients were presented with a matrix
      containing four objects in different positions, and required to detect a change
      in the location, colour or shape of one of the objects following presentation of
      a brief visual mask. Parietal patients were selectively impaired in detecting
      location changes, regardless of the horizontal position of the object in the
      matrix, relative to colour and shape changes. This deficit of spatial working
      memory was not apparent for neglect patients with lesions that spared the
      parietal cortex. We conclude that the human parietal cortex is crucially involved
      in the updating and maintenance of spatial representations across saccades, and
      that neglect arising from parietal damage causes impairment in these re-mapping
      mechanisms.

PMID- 15156796
TI  - Geographic information has to be spatialized to be neglected: a representational
      neglect case.
AB  - A patient with unilateral neglect had to evoke mentally the map of France in two
      different conditions. In the first condition, he was asked to build an iconic
      representation of the map of France and to list all the towns that he could 'see'
      on this mental image within two minutes. In the second condition, he had to
      remember and name as many French towns as possible within two minutes, without
      being instructed to form a mental image. Left representational neglect was
      observed in the first condition only, i.e., when an iconic representation was
      required. These findings, which were replicated four months later, suggest a dual
      mode of coding, retrieval, or both, of geographic information and show that,
      although topographic, geographic data has to be spatialized to be neglected.

PMID- 15156797
TI  - The number space and neglect.
AB  - Recent cognitive models of numerical abilities have postulated that number
      processing may in part rely on a representation of quantities where magnitude is
      organized by spatial proximity, along a "mental number line" extending from left
      to right. We describe four experiments that examined whether such a spatial
      representation of number would be affected by the presence of unilateral neglect
      after right hemisphere damage. When asked to judge whether a single number shown
      at fixation was smaller or larger than "5", patients with neglect were
      selectively slower to respond to "4", but when asked to compare numbers to "7"
      they were selectively slower to respond to "6". This is consistent with a
      representational deficit for numbers located to the left of a reference point
      along the mental number line and was not found in other right brain-damage
      patients without neglect. No effect of represented number position was found in a
      non-numerical task requiring judgements of the physical size of single digit
      characters. Finally, when asked to classify numbers as indicating hours earlier
      or later than six o'clock, neglect patients showed a reverse pattern with slower
      responses to numbers larger than "6', consistent with a representational deficit
      for hour numbers located on the left side of an imagined clock-face. Our findings
      demonstrate that unilateral spatial neglect may produce specific representational
      deficits in number processing that implicate different spatial representations
      according to the task demands.

PMID- 15156798
TI  - Surgical video systems.
AB  - A surgical video system (SVS) is an integration of components used to perform
      minimally invasive surgery (MIS). In the operating room, an SVS consists of an
      endoscope, an attached video camera, a light source, a video processor, and one
      or more video displays. A single SVS can generally be used in any type of MIS
      procedure (e.g., general, orthopedic, urologic), provided that it is equipped
      with the appropriate type of endoscope. In this Evaluation, we tested seven
      systems from six manufacturers. We found that, on average, three-chip systems
      provide better overall image quality than one-chip systems. Three systems were
      judged as providing image quality slightly superior to that of all the other
      systems; however, the level of subjectivity involved in judging performance
      suggests that users should perform in-house trials before purchase. All the
      evaluated systems performed relatively well in performance testing, but most
      systems were rated Fair or Poor in several human factors and safety tests. In
      fact, only two systems did not receive any Poor ratings in the Light Source
      Safety Features tests. Although users bear much of the responsibility for
      ensuring that light sources are used safely, most manufacturers have not made
      simple design changes that would make unintentional misuse less likely. We would
      be more likely to rate systems that still exhibit these safety issues in the
      future as Not Recommended or Unacceptable.

PMID- 15156800
TI  - Disconnecting wall gas can interrupt ventilation on Drager Evita 2 dura and Evita
      4 ventilators: revised recommendations.

PMID- 15156799
TI  - Embolectomy catheter tip breaks off--whereabouts unknown.

PMID- 15156801
TI  - Inserting parameter modules upside down can cause shutdown of Datex-Ohmeda
      Monitors: revised recommendations.

PMID- 15156802
TI  - 75 years of serving: a look back at the issues and challenges that shaped GHA.

PMID- 15156803
TI  - 2004 Distinguished Service Award winners. Dr David Apple, Jr. Committed to the
      prevention of catastrophic injuries.

PMID- 15156804
TI  - 2004 Distinguished Service Award winners. Wayne T. Sikes. Dedicated to ensuring
      patients receive quality health care.

PMID- 15156805
TI  - St. David's: a matter of control.

PMID- 15156806
TI  - Ten year experience with use of Ilizarov bone transport for tibial defects.
AB  - Tibial defects greater than 4 cm and secondary to high-energy trauma or
      debridement for infected nonunion pose a significant challenge to the treating
      orthopaedic surgeon. Twelve patients who had been treated with Ilizarov bone
      transport for tibial defects over the past ten years were retrospectively
      reviewed. All patients were male with an average age of thirty-two. Ten of the
      twelve limbs were categorized as Grade IIIB fractures initially. The average
      tibial defect at initiation of bone transport was 9.45 cm (range 4 to 20 cm). The
      mean external fixator time (EFT) was 16.7 months with a mean external fixator
      index (EFI) of 2.0 months per centimeter. There were a total of 36 complications.
      Twenty were minor, fourteen were major without sequelae and two were major with
      sequelae. Overall bone results were good or excellent in nine patients. Overall
      functional results were good or excellent in eight patients. Ten patients
      achieved union after Ilizarov bone transport. Use of Ilizarov bone transport can
      be an effective tool for treating large tibial defects. However, the treatment
      time is lengthy with a considerable risk of complications.

PMID- 15156807
TI  - Radiosonographic substantiation of algorithms for examination of patients during
      operative lengthening of the tibia.
AB  - The muscles of 70 patients with lower limb shortening due to various etiologies
      were studied using three radiographic diagnostic methods: contrast radiography
      (CR), ultrasonography (US), and computed tomography (CT). The studies were
      performed before surgery, during lengthening using the Ilizarov external fixator,
      during the fixation period following distraction, and after apparatus removal.
      The data compiled using these modalities described alterations in the muscles
      during lengthening which enabled us to develop algorithms for patient examination
      during the process of lower extremity lengthening with the aim of solving
      tactical tasks.

PMID- 15156808
TI  - The effects of radiofrequency bipolar thermal energy on human meniscal tissue.
AB  - This study performed the first in vitro histological analysis of the effects of
      bipolar thermal energy on human meniscal tissue. Sixteen fresh human menisci were
      mounted on a cutting block and placed in a water bath simulating an arthroscopic
      environment. Each specimen was divided into four sections and randomized to one
      of four treatment options: 1. thermal ablation with a bipolar multielectrode 3 mm
      Covac wand (power 3 setting); 2. thermal ablation with a bipolar multielectrode 3
      mm Covac wand (power setting 7); 3. resection with a scalpel blade; and 4.
      resection with a motorized 4.5 full-radius resector. Six micron sections were cut
      and stained with Hematoxylin and Eosin and Masson's trichrome stain. Menisci were
      evaluated for the contour of the cut edge: straight, jagged, frayed, or combined.
      The zone of thermal necrosis and zone of thermal alteration were determined by
      examining the differential staining of the connective tissue and measuring the
      affected area. Menisci treated with the bipolar thermal probe were noted to have
      a smoother contoured edge in comparison to motorized cutters. The zone of thermal
      penetration for the Arthrocare power setting 3 averaged 0.18 mm (range: 0.09 to
      0.20; SD 0.04) and for Arthrocare power setting 7 averaged 0.33 mm (range: 0.26
      to 0.36; SD 0.03). The difference in thermal penetration between Arthrocare power
      settings 3 and 7 was 0.15 mm. This was statistically significant at p < 0.0001
      (95% CI: 0.11 to 0.19 mm). The zone of thermal penetration was non-existent for
      the shaver and scalpel groups. This study provides the first histological
      description of the effects of bipolar radiofrequency energy on meniscal tissue.
      It demonstrates that there is intra-substance thermal penetration and alteration
      of the meniscal tissue. Its clinical significance is unclear and further in vivo
      studies are needed to address its clinical applicability.

PMID- 15156809
TI  - Interobserver reliability and intraobserver reproducibility in suprascapular
      notch typing.
AB  - The size and shape of the suprascapular notch may be a factor in suprascapular
      nerve entrapment. The suprascapular notches of 623 scapulae were digitally
      photographed and used to determine notch type and area. Three researchers used to
      different classification systems for suprascapular notch typing. These systems
      were compared for interobserver reliability and intraobserver reproducibility
      using the kappa test. The mean kappa value for the classification used by
      Rengachary and colleagues was 0.468 and for the classification used by Ticker and
      associates was 0.531 for the inferior border of the notch and 0.736 for the
      superior border of the notch. The classification system used by Ticker and
      associates was more reliable and reproducible and produced both a superior and an
      inferior classification, making it possibly more clinically relevant than the
      classification system used by Rengachary and colleagues.

PMID- 15156810
TI  - Comparison of two headless screw designs for fixation of capitellum fractures.
AB  - In order to determine the effects of two different headless screw designs on
      fixation of simulated capitellum fractures six matched pairs of embalmed humeri
      had simulated capitellum fractures created. Fixation with Acutrac compression
      screws was compared to Herbert screws in a matched pair experimental design. All
      specimens were cyclically tested with simulated physiologic loading. Both
      displacement of the capitellum as a function of the number of cycles and failure
      loads were determined. Fixation by the Acutrac screws was significantly more
      stable than Herbert screws at 2000 cycles, 0.17 mm wersus 1.57 mm (p < 0.02) The
      Acutrac fixation also had a higher failure load, 154 N versus 118 N (p < 0.05).
      The Acutrac screws tested in this biomechanical study provided more stable
      fixation of simulated capitellum fractures than Herbert screws. This appears to
      be related to the design of these screws.

PMID- 15156811
TI  - The role of caudal epidural injections in the management of low back pain.
AB  - The value of caudal epidural steroid injections (CEI) in treatment of low back
      pain and sciatica is controversial. It is believed that CEI are mainly effective
      in treating acute radiculopathy at intermediate term follow up and have no long
      term benefit. The objective of this study was to evaluate the role of CEI in the
      management of low back pain. This study reviews all patients with low back pain
      and sciatica treated with CEI in a one-year period (1997) in the orthopaedic
      department at Aberdeen. The case notes of 163 out of a possible 175 patients (87
      female 76 male) with mean age of 51 years (range: 17 to 88 years) were reviewed.
      Data collected included primary symptoms, presentation time, presumed diagnosis,
      MRI diagnosis, grade of the surgeon ordering and performing the procedure, the
      quality and duration of response, and final outcome. Patients were regarded as
      having an Excellent response if they had good or excellent pain relief for more
      than 3 months, a Good response (6 weeks to 3 months), Fair (4 to 6 weeks), Brief
      (any pain relief for less than 4 weeks), and No relief. Forty-one percent of
      patients had either an excellent/good response to CEI while 34% were no better or
      worse. Patients presenting acutely or with predominantly leg pain symptoms did
      not respond any better to the CEI than chronic presentations or low back pain
      alone. Only 36 of 73 patients who were discharged had an Excellent/Good response.
      Therefore the response to CEI did not influence the decision to discharge half of
      the patients. The experience of the surgeon performing the procedure did not make
      a difference in the outcome. We found that the outcome of CEI was unpredictable.
      The clinical value of CEI remains unproven. The decision to perform the procedure
      may well remain a matter of personal choice and experience.

PMID- 15156812
TI  - Loading of the acetabulum by polyethylene and all-ceramic inserts in metal-backed
      acetabular cups.
AB  - Both static and dynamic loads were applied to metal-backed acetabular cups with
      ceramic or polyethylene inserts and the resulting load transmissions at a
      simulated bone interface were determined. Perfect fit and under-sized and over
      sized cavities were prepared in simulated bone substrates, lined with Fuji
      pressure sensitive film, and acetabular cups inserted with physiological loads.
      The magnitude and location of contact forces between the cup and bone were
      measured. These cups were then subjected to a controlled impact load and the
      intensity and frequency of the loads transmitted to the substrate were
      determined. The results suggest that a polyethylene backing for ceramics is not
      necessary as there were no major differences in the static and dynamic stresses
      transmitted to the cup-bone interface with all polyethylene or ceramic inserts.

PMID- 15156813
TI  - A new test for bipolar prosthesis disassociation.
AB  - Because of several failures by dissociation of a redesigned bipolar prosthesis, a
      new, dynamic test was developed. This dynamic cam-out test represents a closer
      simulation of one possible clinical mechanism of bipolar disassociation. The
      results of dynamic testing are affected by the bipolar design, particularly the
      locking mechanism that was the problem with the redesigned prosthesis.

PMID- 15156814
TI  - Angioleiomyoma of the Achilles tendon.
AB  - Angioleiomyoma, a relatively rare tumor of smooth muscle origin, has been
      reported in many anatomical sites. We present a patient who was referred with a
      diagnosis of nodular Achilles tendinopathy. At exploration, the mass was excised,
      and histopathology revealed it to be an angioleiomyoma. Tumoral masses should
      form part of the differential diagnosis of a subcutaneous lesion on an extremity,
      particularly the lower limb.

PMID- 15156816
TI  - Tuberculous pseudotumor of the proximal end of the fibula. A case report.
AB  - A 72-year-old asian woman who had immigrated from Vietnam 10 years ago presented
      with a soft tissue mass around the proximal fibula. Conventional radiographs and
      magnetic resonance imaging demonstrated a destructive lesion of the head of the
      fibula with an intact superior tibiofibular joint and an abscess surrounding the
      destroyed bone. Histopathology obtained by a CT-guided needle biopsy revealed
      necrotizing epithelioid granulomata without demonstrating acid-fast bacilli.
      However, culture grew Mycobacterium tuberculosis. When tuberculosis affects the
      end of a long tubular bone, the adjacent synovial joint is usually involved.
      Cases where joint involvement does not occur are extremely rare and unusual. We
      report such a case.

PMID- 15156815
TI  - Metasynchronous bilateral Achilles tendon rupture.
AB  - Although Achilles tendon ruptures are a common occurrence, bilateral ruptures of
      the Achilles tendon are not. We present the case of a 33-year-old female who
      sustained metasynchronous (i.e., very close in time) bilateral ruptures of her
      Achilles tendons with no obvious predisposing factors. She was treated using a
      percutaneous technique and six months following surgery has returned to her
      normal activities.

PMID- 15156817
TI  - Surgeon volunteerism. One orthopaedic surgeon's perspective.

PMID- 15156819
TI  - Osteochondral lesions of the talar dome.

PMID- 15156818
TI  - Prevention of heterotopic ossification at the elbow following trauma using
      radiation therapy.
AB  - The objective of this study was to determine the efficacy of postoperative single
      dose radiation therapy of 700 centigray on fracture/dislocations of the elbow in
      the prevention of heterotopic ossification. Eleven patients were reviewed for
      this study. Each patient sustained high-energy trauma to the extremity causing a
      fracture/dislocation of the elbow. After open reduction and internal fixation, a
      postoperative single dose of 700-centigray radiation therapy was administered to
      the patients within 72 hours of surgery. Primary outcome measurements were
      clinical physical examination of range of motion and radiographic analysis of
      heterotopic bone formation at 12 months follow-up. Three of eleven patients (27%)
      had radiographic evidence of heterotopic ossification formation. Ten of eleven
      patients (91%) however, were without functional limitations. All fractures healed
      without complications. There were no complications from the radiation therapy. A
      single dose of 700-centigray radiation therapy postoperatively within 72 hours
      may lessen the functional loss from heterotopic ossification formation without
      effecting healing at the fracture site.

PMID- 15156820
TI  - Management of acute scaphoid fractures.
AB  - Scaphoid fractures are a common injury in young, active populations. Non
      displaced fractures have a high union rate if promptly treated with cast
      immobilization. Displaced fractures and proximal pole fractures are best treated
      with operative fixation. There are a variety of techniques and implants available
      to the surgeon. The surgical approach and fixation device should be based on
      fracture characteristics and surgeon experience. Operative fixation of non
      displaced fractures is an option in patients who would prefer to avoid prolonged
      cast immobilization.

PMID- 15156822
TI  - Surgical management of the middle age arthritic knee.
AB  - There are several options available for management of the middle-aged arthritic
      knee. Arthroscopic techniques continue to evolve, but the true natural history of
      the arthritic process is probably not altered. Good to excellent short-term
      results can be expected with proper patient selection. Patient counseling is
      important in order to discuss the nature of the underlying disease process, the
      limited goals of the arthroscopic procedure, and the possible need for further
      surgery. Proximal tibial osteotomy for the treatment of medial compartment
      osteoarthritis can be effective for as long as 15 years. There is a deterioration
      of results over time that can often be correlated to the degree of correction
      achieved. Strict selection criteria can maximize success. Revision surgery to
      total knee replacement, albeit technically difficult, is a viable option with
      results similar to primary TKR. Unicompartmental knee arthroplasty remains a
      controversial procedure as its indications continue to evolve. Good to excellent
      results can be expected in 80% to 90% of patients at 10 years follow-up.
      Unicompartmental knee arthroplasty occupies a special niche in the treatment of
      unicompartmental osteoarthritis and supplements total knee replacement and high
      tibial osteotomy surgery.

PMID- 15156821
TI  - Athletic ergogenic aids.
AB  - Claims championing exotic substances that produce healing or ergogenic powers
      have been around for centuries. The competitive, peer-pressured environment
      enveloping today's athletes and adolescence makes these groups particularly
      susceptible to the uproar surrounding the current ergogenic aid market.
      Presently, it seems that rumor and anecdotal information overwhelms the available
      scientific data. While there is evidence that some touted ergogenic aids do
      indeed enhance performance, there are many unanswered questions about product
      safety, efficacy, and long-term consequences. A working knowledge of specific
      ergogenic aids is essential for the treating physician in order to best advise
      patients and athletes as to the possible benefits and risks of any substance they
      may be using.

PMID- 15156823
TI  - Rheumatoid arthritis of the wrist.
AB  - The wrist is the most commonly involved joint in the upper extremity of patients
      with rheumatoid arthritis. Up to 75% of patients will develop wrist problems
      during the course of the disease. Cartilage degeneration and synovitis cause the
      typical skeletal erosions, ligamentous laxity, deformity, and tendon problems
      seen in the disease. Treatment involves a multidisciplinary approach with careful
      coordination of the primary care physician, rheumatologist, orthopaedic surgeon,
      and other members of the care team. As rheumatoid arthritis is a systemic,
      polyarticular disease, it is critical to consider the entire patient in any
      management decision. Initial management is usually non-operative and involves
      pharmacological treatment, activity modification, and possibly bracing. Operative
      treatments are geared to limit the negative effects of the disease, namely pain,
      loss of function, and deformity. Numerous procedures have been described. Common
      procedures from tenosynovectomy/synovectomy, distal radio-ulnar joint
      arthroplasty, arthrodesis, and total wrist arthroplasty are reviewed.

PMID- 15156824
TI  - SLAP lesions of the shoulder.
AB  - SLAP lesions are becoming a more recognized cause of shoulder pain and
      disability. The diagnosis of these lesions is difficult due to vague symptoms and
      high degree of overlap with other shoulder disorders, and this requires a high
      index of suspicion. Advances in MR arthrography may lead to advances in
      preoperative diagnosis of labral tears, but definitive diagnosis, classification,
      and management is greatly facilitated with the use of the shoulder arthroscopy.
      Further basic science and clinical research should enhance our ability to manage
      patients with these lesions effectively.

PMID- 15156825
TI  - Liberal bioethics and contested surgeries.

PMID- 15156826
TI  - Intersex surgery.

PMID- 15156827
TI  - Extraordinary litmus tests.

PMID- 15156828
TI  - Stem cell banks: some consequences.

PMID- 15156829
TI  - Posthumous reproduction guidelines in Israel.

PMID- 15156830
TI  - Like a river.

PMID- 15156831
TI  - International human rights law and mental disability.

PMID- 15156832
TI  - Is the patient always right?

PMID- 15156833
TI  - Pushing the borders: the moral dilemma of international Internet pharmacies.

PMID- 15156834
TI  - Emily's scars. Surgical shapings, technoluxe, and bioethics.
AB  - Increasingly, medicine is used to remodel, revise, and revamp as much as to heal
      and mend. It is tempting to say that people make merely personal choices about
      these new uses. But such choices have implications for everybody, and they ought
      to be made cautiously, slowly, and in a way that opens them to discussion.

PMID- 15156836
TI  - ES cell research: in the shadow of the ban.

PMID- 15156835
TI  - Enough. The failure of the living will.
AB  - In pursuit of the dream that patients' exercise of autonomy could extend beyond
      their span of competence, living wills have passed from controversy to
      conventional wisdom, to widely promoted policy. But the policy has not produced
      results, and should be abandoned.

PMID- 15156837
TI  - Without borders.

PMID- 15156838
TI  - Caregivers of patients with chronic pain: responses to care.
AB  - PURPOSE: To explore the caregiving role of nonprofessional caregivers of patients
      with chronic pain. METHOD: Descriptive study of 30 caregivers. FINDINGS: Twenty
      eight (93%) caregivers demonstrated 1 to 6 defining characteristics of caregiver
      role strain, and 2 (7%) had at least two factors of risk for caregiver role
      strain. CONCLUSION: Caring for patients with chronic pain has a meaningful impact
      on caregivers' lives. PRACTICE IMPLICATIONS: Caregivers of patients with chronic
      pain deserve care, not only with the objective of optimizing relief for the
      patients, but also to help them seek and attain optimal functionality.

PMID- 15156839
TI  - Formulation of a plan of care for culturally diverse patients.
AB  - PURPOSE: To formulate a plan of care for a culturally diverse population and
      develop a resource for the healthcare team in providing culturally competent
      care. DATA SOURCES: Books, journal articles. DATA SYNTHESIS: Healthcare workers
      are challenged to provide appropriate care for an increasingly diverse
      population. A cluster of nursing diagnoses were used to develop a plan of care
      addressing the unique challenges of caring for a diverse population served by a
      community hospital. CONCLUSION: A care plan was devised and inserted into the
      nursing diagnosis-based nursing documentation computer system for easy access
      when needed. PRACTICE IMPLICATIONS: A care plan for a diverse population can
      promote respectful and excellent care for every patient.

PMID- 15156840
TI  - The changing face of AIDS.

PMID- 15156841
TI  - Unserved, unseen, and unheard: integrating programs for HIV-infected and HIV
      affected older adults.
AB  - This article explores the parallel structures and service delivery systems of the
      Older Americans' Act and the Ryan White CARE Act, argues that social workers
      should have a working knowledge of both pieces of public policy, and suggests
      integration or coordination of aging and HIV services. Two vignettes illuminate
      the issues and implications for HIV and aging network social workers. The authors
      argue that HIV social workers should know more about services for older people
      and that gerontological social workers should know more about HIV services so
      that HIV-infected and HIV-affected older people do not remain unserved, unseen,
      and unheard.

PMID- 15156842
TI  - Social support and maintenance of safer sex practices among people living with
      HIV/AIDS.
AB  - The study discussed in this article addressed the relationship of social support
      to the maintenance of long-term safer sex practices of 360 HIV-positive adults
      recruited from outpatient medical facilities. Medical professionals, friends, and
      siblings were reported the most frequent sources for assistance, whereas regular
      sexual partners, medical professionals, and community organizations were rated as
      the most helpful. Differences in social support use across ethnic, gender, and
      sexual orientation groups were observed. Those engaging in safer sex practices
      perceived the support they received as more helpful. These findings emphasize the
      link between positive support networks and avoidance of high-risk sexual behavior
      in HIV-positive individuals. Implications for the delivery of culturally
      appropriate, gender-specific, and community-based interventions are discussed.

PMID- 15156843
TI  - Health care seeking for HIV/AIDS among South Asians in the United States.
AB  - Health-related behavior is a function of the sociocultural and environmental
      contexts in which it occurs. With South Asian immigrants, a comprehensive
      approach that focuses on community and individual factors may be more effective
      than an individualistic one. This article explores the factors that may influence
      HIV/AIDS-related health care seeking by South Asian immigrants to the United
      States. It focuses on South Asians from Bangladesh, India, and Pakistan. The need
      to involve the community in any intervention process is discussed. An
      understanding of the determinants of HIV-related health care seeking and
      behavioral change factors can help social work practitioners develop effective
      interventions for and with South Asian immigrants.

PMID- 15156844
TI  - Keeping and disclosing a secret among people with HIV in Israel.
AB  - This study examined the association of key variables with the intention to
      disclose and actual disclosure to an additional significant other of being HIV
      infected. Sixty-five participants were recruited from five AIDS/HIV centers in
      Israeli hospitals. Participants completed questionnaires at entry to the study.
      They were asked about the extent to which they had already disclosed being HIV
      infected, their intentions regarding future disclosure, and their emotional
      state; six months later their disclosure was examined. Depression and shame
      affected the intention to disclose the secret. Disclosure was associated with
      being male, having a high level of depression and shame, and having a low level
      of education. Participants with high levels of guilt who stated that they
      intended to disclose the secret were most likely to have done so. Implications
      for practice are discussed.

PMID- 15156845
TI  - Stresses on grandparents and other relatives caring for children affected by
      HIV/AIDS.
AB  - This study investigated the needs of relative caregivers of children in the child
      welfare system whose parents had HIV. Families of children supported by the state
      child welfare agency were invited to participate in the study; 17 families
      reported that HIV affected them and 11 families did not identify HIV as an issue.
      The findings indicate that complex emotional and behavioral issues stressed the
      HIV-affected kin caregivers; these issues included the children's behavioral
      problems, HIV-related concerns, adolescent issues, emotional difficulties, and
      sexual abuse, HIV-affected caregivers had more concern about their health and
      multiple roles. Nonaffected caregivers were less likely to report severe
      parenting stress and more likely to report financial stress. HIV-affected
      caregivers require attention and intervention by social workers, child welfare
      workers, and case managers.

PMID- 15156846
TI  - The impact, meaning, and challenges of work: perspectives of individuals with
      HIV/AIDS.
AB  - This study used a qualitative methodology to examine the work needs and
      experiences of 29 individuals with HIV/AIDS. Findings revealed the value and
      significance of employment, concerns related to social security benefits and
      discrimination, informal and formal supports and barriers, and the needs of
      unemployed compared with employed individuals. Implications consider the best
      methods of helping individuals with HIV/AIDS obtain or maintain employment.

PMID- 15156847
TI  - Positive impact: a community-based mental health center for people affected by
      HIV.

PMID- 15156848
TI  - Challenges for social work in hemophilia care.

PMID- 15156849
TI  - Current trends and the future of HIV/AIDS services: a social work perspective.

PMID- 15156850
TI  - [The life history of Alexander Numan (1780-1852) during his time in Groningen].
AB  - Until the time Numan took on his professorship at the newly established
      Veterinary School in Utrecht in 1822, he had lived in the Province of Groningen.
      In order to understand why the minister of Public Education appointed a village
      doctor from the north of the country as professor for the practice of veteriary
      medicine, and after some years as director of the school, it was felt essential
      to investigate his earlier life period. The main sources used are two obituaries,
      resp. written by his son who was a professor of Law at Groningen University, and
      by his friend prof. Willem Vrolik who was the secretary of the Academy of
      Science, supplemented by family histories and some archival research. After a
      short description of his descent, youth adn education follows the main part
      devoted to his writings, his medical practice and membership of the Provincial
      Medical Commission and the Commission for Agriculture. In an appendix some
      genealogical data are presented on the family of his wife and their children.
      Alexander lost his father, who was a minister of the Reformed Church, when he was
      ten years old. He received his education in the circle of family members. A
      brother of his father, also a minister, teached him Greek and Latin. After this
      uncle had left the province, he lived in the home of another minister who teached
      him the modern languages. As this man was involved in politics of the Baravian
      Republic, young Alexander was exposed to many discussions on the polity of the
      State. After his mother had remarried with a medical doctor, this man, and also
      his brother who had a medical practice in another part of the province,
      complemented the education with an introduction in the sciences. Experiences in
      their dispensaries, where some knowledge of botany and chemistry could be
      obtained, and discussions when accompanying them on their visits to patients,
      were decisive in the choice of his profession. Only at the age of twenty he
      entered the Medical Faculty of Groningen University. Thanks to the elaborate
      preparatory studies, he was able to finish in three years. In 1804 he defended
      his thesis on a pharmaceutical subject. Immediately afterwards he set up practice
      in a village nearby the town of Groningen. He married two years later Catharina
      Dorothea Star Lichtenvoort, daughter of a wealthy lawyer. They had two children,
      a son born in 1807, and a daughter, born in 1808. Alexander built a flourishing
      medical and obstetrical practice, extending over a very large area, he teached
      apprentices in his dispensary, translated articles and a book by C.W. Hufeland
      and published case histories from his own practice. Several lectures given at
      local scientific societies were published. One deal with his thoughts on and
      experiences with animal magnetism, a topic very much en vogue in those days,
      especially in the Groningen Medical Faculty. In 1812 his translation of
      Allenmeines Viehazneibuch by J.N. Rohlwes was published, showing his interest in
      veterinary matters. As a book appeared not to be satisfatory enough for the needs
      of the Dutch farmers, he was invited by the board fo the 'Society for Public
      Welfare' (Maatschappij tot Nut van het Algemeen) to write an adapted version.
      This handbook (first ed. 1819) would receive many editions throughout the 19th
      century. This book together with his capacities as a teacher, his broad interests
      in medical and agricultural affairs, great scientific curiosity and appreciation
      by colleagues met in the several commissions made him an obvious candidate for
      the new post in Utrecht. Although he felt it difficult to leave his beloved
      homeland and terminate his practice, he felt great pride in accepting the post
      that would give him the opportunity to found a new discipline in his country. To
      be useful to society was one of the great motives of his life.

PMID- 15156851
TI  - [Development of animal husbandry in Groningen in the 18th and 19th century; a
      broad outline].
AB  - This overview is mainly focussed on the clay area forming the northern half of
      the province. It is the wealthiest and most characteristic part, being cultured
      since the Middle Ages as testified by the many churches that even small villages
      were able to construct. About 1700 the province of Groningen enjoyed already a
      modern economy, fitting in with that of the other coastal areas of Friesland,
      Zeeland and Holland (the last mentioned was the richest region of the world in
      the 17th and 18th century). As aspects of modernity at that time can be
      considered: 1) the use of modern agricultural methods with higher yields per
      hectare and higher milk yields per cow than produced in the land provinces on the
      sandy soils; 2) Agriculture was aimed at earning money by selling of hte
      products. In opposition to the farmers in the land provinces, who mainly produced
      for subsistence farming, the farmers in the coastal areas produced for the trade;
      3) A high degree of specialization was found in the rural areas. 30-40% of the
      families had own farms, 25% of the population were labourers, owing only small
      pieces of land and the rest of the working population had occupations outside
      agriculture (craftmen, shopkeepers, shipmasters, merchants etc.). Whereas on the
      sandy soils practically every family owned a farm, be it mostly a very small one.
      After reviewing the changes in the distribution of land in use of the production
      of fieldcrops or for meadows-always in function of the market value of the
      products-and after a discussion of type of cattle husbandry (breeding, fattening,
      dairying) it is concluded that a relative decrease of the importance of cattle
      husbandry in the clay region during the 18th - 19th century can be observed.
      Intensification of land use had a positive effect on crop-production. The much
      heard opinion that the cattle plague epizootic of 1768-1786 caused a transition
      in land use through a switch from animal husbandry to arable farming, is not held
      by the author. Economic factors were of prime importance here. The introduction
      of fertilizer in the 19th century took away the necessity to keep cattle for
      manure. And mechanization did the same for the horse in the 20th century. In some
      parts of the clay region, however, cattle husbandry returned in the second half
      of the 20th century, due to the low prices of the fieldcrops. The arable land is
      then transformed again in meadows. Attention is given to the role of veterinary
      care given by the farmers themselves and in a later phase by veterinary
      professionals.

PMID- 15156852
TI  - [Journal of the Turkish Society of Algology indexed in Index Medicus].

PMID- 15156854
TI  - [Threadworm].

PMID- 15156855
TI  - Safety of learning disability patients must be improved.

PMID- 15156856
TI  - Education needs review.

PMID- 15156857
TI  - Survey raises concerns.

PMID- 15156858
TI  - [The 105th Congress of the Japanese Society of Otolaryngology. Hiroshima, Japan.
      May 13-15, 2004. Abstracts].

PMID- 15156859
TI  - Euthanasia and persistent vegetative state individuals: the role and moral status
      of autonomy.
AB  - This paper offers a philosophical consideration and evaluation of several
      different criteria of moral standing, and discusses their implications for
      persistent vegetative state (PVS) individuals who were once competent. It is
      argued that the only criterion PVS individuals meet is that of being human, which
      is not the best test of moral standing. Accordingly it is, in principle, morally
      acceptable to perform passive or active euthanasia on PVS individuals or to use
      their bodies for research or for organ harvest. Nevertheless, the autonomous
      choices made by the persons the PVS individuals used to be can still impose moral
      obligations. Indeed, it is argued that the capacity for autonomy is a
      particularly appealing criterion of moral standing, and that the implications of
      this standard for PVS individuals confirm that appeal.

PMID- 15156860
TI  - [The Japanese Respiratory Society guidelines for the diagnosis and treatment of
      chronic obstructive pulmonary disease].

PMID- 15156861
TI  - Psychological issues in euthanasia, suicide, and assisted suicide.
AB  - This paper reviews various life-ending techniques such as euthanasia, suicide,
      and assisted suicide in order to better address the psychological issues related
      to these actions. Specific attention is paid to investigating when a death is
      deemed to be appropriate and the role that the level of appropriateness should
      play in the decisions of individuals to terminate a life. In addition, a number
      of additional psychological concepts such as locus of control and subjective
      norms are examined in terms of their importance for decisions regarding
      euthanasia and suicide.

PMID- 15156862
TI  - Assessing right to die attitudes: a conceptually guided measurement model.
AB  - This article discusses the current status of research regarding the assessment of
      attitudes toward euthanasia and other right to die constructs with a focus on
      conceptual and methodological issues hindering advancement in this area. Two
      models are presented: a conceptual model for differentiating the various right to
      die constructs, and a measurement model to guide scale development and
      refinement. The conceptual model defines the right to die constructs as a
      function of locus of decision and locus of action. Health status and age are
      hypothesized as important factors that in some instances are defining attributes
      in right to die constructs and in other instances are factors influencing
      people's attitudes toward the right to die. The measurement model considers the
      importance of construct specificity, individual characteristics, and conviction
      in the assessment of right to die attributes. An extant euthanasia attitude scale
      is presented and evaluated in terms of the models to demonstrate how they may be
      useful for advancing attitude research in this important area.

PMID- 15156864
TI  - On gender role violations and judgments made about euthanasia: a research note.
AB  - The impact of perceived gender role violations on the willingness of evaluators
      to label a deadly act to "end suffering" as euthanasia was explored in two
      studies. It was predicted that "killing" (even mercy killing) would be perceived
      as more role contradictory for a female actor than for a male actor. Therefore,
      it was expected that the deadly actions of a female actor would be judged as less
      justified (i.e., less likely to be labeled as euthanasia) than the same action
      committed by a male actor. A total of 486 undergraduates participated in one of
      two studies. It was found that although perceptions of justification for a deadly
      act were clearly influenced by whether or not the method of action taken was
      direct and proactive (commission) vs. indirect and passive (omission), the gender
      of the actor did not impact differently on the judgments of the participants.
      Possible explanations and future research directions are discussed.

PMID- 15156863
TI  - Community attitudes on the family of issues surrounding the death of terminal
      patients.
AB  - In two studies, respondents made recommendations for the medical treatment of a
      terminally ill elderly woman. The woman was or was not experiencing intractable
      pain, and had requested either heroic medical efforts or euthanasia. Respondents'
      recommendations were influenced by both the specific wishes of the patient and
      the pain the person was experiencing. However, participants were not completely
      swayed by the patient's wishes: only about half of the sample recommended
      euthanasia even when the patient was in intractable pain and had requested death;
      also, many subjects would not resuscitate the patient whose heart or lungs
      failed, even though she had requested heroic measures. Respondent attitudes
      toward euthanasia predicted recommendations in the expected directions. We
      suggest that there is less dissent on the issues that arise for medical
      treatments at the end of life than has been widely assumed.

PMID- 15156865
TI  - [The 77th general meeting of Japanese Leprosy Association. Saitama, Japan. May 20
      22, 2004. Abstracts].

PMID- 15156866
TI  - Euthanasia on trial: examining public attitudes toward non-physician-assisted
      death.
AB  - This study investigated the influence of various contextual effects on the
      decisions of subjects evaluating a case of nonphysician-assisted suicide.
      Subjects viewed a videotaped deposition of an individual emotionally or
      nonemotionally describing how he assisted in the death of his terminally ill wife
      by disconnecting her respirator or shooting her in the head. The deposition was
      followed by jury instructions that outlined the duties of the subject and, in
      some cases, was followed by a nullification instruction that informed the
      subjects of their right to ignore the law in this case if they felt it would
      culminate in an unfair verdict. After viewing the videotape, subjects were asked
      to rate the guilt of the individual as well as their confidence in this rating.
      Results indicate that the means of death and the type of instruction
      significantly affect guilt ratings. The implications of these findings are
      discussed.

PMID- 15156868
TI  - Practical reasons and reasonable practice: the case of euthanasia in The
      Netherlands.
AB  - Since the early 1970s the issue of euthanasia has been intensely debated in The
      Netherlands. Through these debates knowledge about medical practices involving
      the end of life was no longer confined to medical or legal quarters, but became
      public to a large extent. Following public opinion changes, the legal reaction to
      euthanasia changed. By prosecuting test cases the public prosecutors allowed the
      Dutch Supreme Court to formulate specific conditions in which euthanasia would go
      unpunished. The political debate about changing the criminal law, which still
      holds that euthanasia is a serious crime, developed at a much slower pace.
      Several extensive empirical studies were undertaken to gain valid knowledge about
      the medical practices. This article is concerned with a presentation of the
      various debates and the changes that took place in the fields of criminal law,
      politics, and medicine. The main conclusion is the hypothesis that a more open
      climate for medical practices concerning the end of life allows society to better
      control these practices.

PMID- 15156869
TI  - Fistula function and dialysis adequacy during ozonotherapy in chronically
      hemodialyzed patients.
AB  - There are a variety of complications related to chronic hemodialysis treatment,
      including thrombosis in hemodialysis access leading to blood recirculation, and
      in turn to the deterioration in hemodialysis effectiveness. Given that ozone
      decreases blood viscosity, increases erythrocyte deformability, and inhibits
      coagulation, the periodic blood ozonation may be of benefit in the attenuation of
      these disturbances. To gain insight into this issue,we originally evaluated the
      impact of ozonated autohemotherapy on recirculation in arteriovenous fistula,
      hemodialysis adequacy, and the frequency of dialyzer reuse. Twelve chronically
      hemodialyzed patients with peripheral arterial disease were enrolled in the
      prospective, placebo-controlled study. Nine sessions of autohemotherapy with the
      exposure of blood to oxygen, as a control, and nine sessions of autohemotherapy
      where the blood is exposed to ozone in a concentration of 50 microg/mL are
      administered in a single-blind manner. Access recirculation is measured by means
      of spectral technology(Crit Line Monitor, HemaMetrics, Kaysville, UT, U.S.A.),
      and hemodialysis adequacy is calculated using the Daugirdas formula and expressed
      as the Kt/V index. The Kt/V index and the frequency of dialyzer reuse do not
      change after ozonated autohemotherapy. Recirculation decreases after ozonotherapy
      in the majority of patients.on average by 35.3%, but the change does not reach
      the level of statistical significance (P = 0.064). We demonstrate that ozonated
      autohemotherapy does not influence dialysis adequacy and the frequency of
      dialyzer reuse. The improvement of fistula function, expressed as a decrease in
      recirculation, is not significant, although seen in the majority of patients.

PMID- 15156867
TI  - Cross-cultural research on euthanasia and abortion.
AB  - Based on cross-cultural studies of euthanasia and abortion, we hypothesized that
      attitudes toward euthanasia and abortion were socioculturally determined. Using a
      2 x 2 factorial design, we examined the effects of culture (America and China)
      and type of death (infanticide and geronticide). We found that students from the
      American culture were less likely to favor infanticide than those from the
      Chinese culture, and that students from the People's Republic of China believed
      infanticide to be more common and more prevalent than geronticide in Chinese
      society. Finally, we found that education, judgment of population density, and
      traditional family values were related to attitudes toward euthanasia, abortion,
      and female infanticide in the Chinese, but not in the American, culture.

PMID- 15156871
TI  - Survey finds 'heart' of nursing is missing.

PMID- 15156870
TI  - The systematic application of ethical codes in the counseling of persons who are
      considering euthanasia.
AB  - As health psychology develops, psychologists and counseling professionals are
      becoming progressively more involved with patients who have chronic terminal
      illnesses such as AIDS, Alzheimer's disease, and cancer. Consequently, they will
      be consulted increasingly by patients, caregivers, and lawyers in cases where
      euthanasia is being considered. There are numerous ethical dilemmas that could
      arise when counseling persons who are contemplating euthanasia. Professionals
      must consider carefully issues such as informed consent, bodily autonomy, respect
      for a person's dignity, patient welfare, as well as responsibility to society.
      The national psychological, social work, and medical associations of North
      America have each adopted a code of ethics. These codes may be used by counseling
      professionals to assist in the resolution of ethical dilemmas that may arise as a
      result of working with persons considering euthanasia. This paper discusses the
      relevance of these codes to the counseling of terminally ill patients.

PMID- 15156872
TI  - Valuing past achievements.

PMID- 15156873
TI  - Difficulties of definition.

PMID- 15156874
TI  - Neonatal euthanasia: attributions of students and nurses.
AB  - An attributional analysis of neonatal euthanasia was undertaken in two studies to
      compare the responsibility attributions of nursing and non-nursing students
      (Study 1) and nurses (Study 2) toward a physician for a critically ill neonate's
      death. In both studies, vignettes about a newborn's death differed with respect
      to the physician's treatment of the critically ill newborn. In the student study,
      the physician was attributed the least responsibility for the newborn's death
      when cardiopulmonary resuscitation was attempted but failed, followed by the
      physician's issuance of either a "Do Not Resuscitate" order or an order to turn
      off the infant's respirator. Greatest responsibility was attributed to the
      physician when he ordered the infant's nutritional and hydration support to be
      terminated. In addition, the student's major (nursing vs. non-nursing) and the
      nursing student's educational cohort impacted the level of physician
      responsibility attributed. In contrast, the nurses' study found that the
      termination of nutritional and hydrational support was viewed as different from
      the physician's other three actions.

PMID- 15156875
TI  - BNA's ruling on tights.

PMID- 15156876
TI  - [The 1st Gastroenterology School. Sarajevo, 8-10 April 2004. Clinical Center of
      Sarajevo University].

PMID- 15156877
TI  - Proceedings of the 2nd Congress of Medical Informatics of Bosnia and Herzegovina
      with international participation. University of Sarajevo, April 18-18 2004.
      Sarajevo.

PMID- 15156878
TI  - Grounded in the reality of their lives: listening to teens who make the abortion
      decision without involving their parents.

PMID- 15156880
TI  - Are we essentially persons? Olson, Baker, and a reply.

PMID- 15156879
TI  - Reconsidering surrogate decision making: Aristotelianism and Confucianism on
      ideal human relations.

PMID- 15156882
TI  - Curing the unique health identifier: a reconciliation of new technology and
      privacy rights.
AB  - The Health Insurance Portability and Accountability Act has mandated the
      assignment of a universal individual health identifier in 2003. Such an
      identifier can increase patient confidentiality, improve patient care, lower the
      cost of services to the patient, enhance administrative efficiency, and increase
      the opportunity for medical research. Nevertheless, national identification
      systems raise concerns about confidentiality and privacy. Instead of a mandatory,
      government-assigned number, this article proposes a technologically multi-tiered
      system that would be administered by a mixed government and private entity.
      Consumers could voluntarily opt-in to the system.

PMID- 15156881
TI  - Governing population genomics: law, bioethics, and biopolitics in three case
      studies.
AB  - Existing scholarship on population genomics has only superficially addressed
      issues of power and political process. Accordingly, questions of politics and
      governance pervade the analysis of three population genomics case studies that
      follow: the Human Genome Diversity Project, Iceland's Health Sector Database, and
      "Clinical Genomics" as defined by the Beth Israel-Ardais collaboration. An
      examination of these case studies reveals that the common law, U.S. regulatory
      law, and international law have not developed the political sophistication to
      make the traditional promises of biomedical ethics--respect for autonomy,
      justice, and beneficence--come to fruition. Further, comparisons of these
      projects illuminate three areas ripe for reframing--informed consent, expert
      ethical oversight, and commercial benefits. Four avenues of reform are suggested.

PMID- 15156883
TI  - Religious identity and the health care market: mergers and acquisitions involving
      religiously affiliated providers.

PMID- 15156884
TI  - Eugenics and equality: does the Constitution allow policies designed to
      discourage reproduction among disfavored groups?

PMID- 15156885
TI  - The moral, ethical, and legal controversy surrounding pluripotent stem cell
      research.

PMID- 15156886
TI  - FDA regulation of human cloning: usurpation or statesmanship?

PMID- 15156887
TI  - Double-take: a second look at cloning, science fiction and law.

PMID- 15156889
TI  - Who owns the human genome? What can ownership mean with respect to genes?

PMID- 15156888
TI  - Cloning and the preservation of family integrity.

PMID- 15156890
TI  - Conjoined twins: can the state mandate sacrifice surgery?

PMID- 15156891
TI  - Triage in the nation's medicine cabinet: the puzzling scarcity of vaccines and
      other drugs.
AB  - For a variety of reasons, vaccines and other critical pharmaceutical products
      have become increasingly scarce in the last few years, and persistent shortages
      involving dozens of essential drugs may imperil the public health. Pressures
      emanating from regulatory agencies, the courts, and insurers have conspired to
      make some lines of the pharmaceutical business less than attractive. Although
      concerns about unpredictable tort liability received most of the blame in the
      past, two other factors may help to account for the latest round of drug
      shortages: stringent federal control of manufacturing facilities and aggressive
      cost-containment efforts that further erode profit margins. Whatever the cause,
      scarce supplies necessitate efforts at rationing that pose their own difficulties
      for health care providers. Policymakers could avoid putting physicians to such
      tough choices regarding patients by focusing on ways to ensure the production of
      adequate quantities of these highly cost-effective medical technologies. Some
      commentators have called for greater public sector involvement, but this Article
      concludes that, in addition to bolstering its emergency stockpiles, the federal
      government instead needs to take steps designed to encourage private
      manufacturers to continue supplying critical pharmaceuticals. To this end, the
      government should adopt more flexible regulations governing manufacturing
      facilities, provide companies with greater protection from the vagaries of tort
      liability, and avoid pursuing excessive cost-control strategies. Otherwise,
      patients may continue to lose access to important therapeutic products.

PMID- 15156892
TI  - It takes two, baby: fathers, the tort of conversion, and its application to the
      abortion of pre-viability fetuses.

PMID- 15156893
TI  - Navigating the slippery slope of frozen embryo disputes: the case for a
      contractual approach.

PMID- 15156894
TI  - Embryos, stem cells, morality and public policy: difficult connections.

PMID- 15156896
TI  - Supporting the work of lesser geniuses: an argument for removing obstructions to
      human embryonic stem cell research.

PMID- 15156895
TI  - Federal funding of human embryo stem cell research: advocating a broader
      approach.

PMID- 15156897
TI  - Stem cell research: is the law preventing progress?

PMID- 15156898
TI  - Abnormal gastroesophageal flap valve is highly associated with endoscopic reflux
      esophagitis after Helicobacter pylori eradication.
AB  - BACKGROUND: Whether or not eradicating Helicobacter pylori worsens reflux
      esophagitis remains controversial. We investigated the relationship between
      gastroesophageal flap valve grading and endoscopic reflux esophagitis (in
      patients with peptic ulcer and gastritis) before and after H. pylori eradication
      in a case controlled study. Whether endoscopic assessment of the gastroesophageal
      flap valve allows prediction of endoscopic reflux esophagitis development or
      exacerbation was also assessed. MATERIALS AND METHODS: A total of 220 patients
      with peptic ulcer or chronic gastritis, who received H. pylori eradication
      therapy, were followed for at least 6 months (range, 6-34 months) for endoscopic
      changes. Another 88 age- and disease-matched H. pylori-positive controls, without
      eradication therapy, were also enrolled. Gastroesophageal flap valve grade (I-IV)
      was assessed using the Hill classification. RESULTS: Endoscopic reflux
      esophagitis incidence was significantly (p < .01) higher in abnormal
      gastroesophageal flap valve (grades III and IV) than in normal gastroesophageal
      flap valve (grades I and II) cases in both H. pylori eradication and control
      groups. The rate of new endoscopic reflux esophagitis after eradication was
      significantly (p < .01) higher in the abnormal than in the normal
      gastroesophageal flap valve group (54.5% vs. 9.1%). By contrast, the endoscopic
      reflux esophagitis exacerbation rate in patients with endoscopic reflux
      esophagitis before eradication was low (4.5%) and endoscopic reflux esophagitis
      improvement was observed in 40.9% of these patients. CONCLUSIONS: These results
      suggest gastroesophageal flap valve grading by endoscopy to be useful for
      predicting the risk of newly developing endoscopic reflux esophagitis after H.
      pylori eradication, in addition to predicting the presence of endoscopic reflux
      esophagitis.

PMID- 15156899
TI  - Recurrent peptic ulcers in patients following successful Helicobacter pylori
      eradication: a multicenter study of 4940 patients.
AB  - OBJECTIVE: Although curative treatment of Helicobacter pylori infection markedly
      reduces the relapse of peptic ulcers, the details of the ulcers that do recur is
      not well characterized. The aim of this study is to describe the recurrence rate
      and specific features of peptic ulcers after cure of H. pylori infection.
      METHODS: This was a multicenter study involving 4940 peptic ulcer patients who
      were H. pylori negative after successful eradication treatment and were followed
      for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured
      patients, background of patients with relapsed ulcers, time to relapse, ulcer
      size, and site of relapsed ulcers were investigated. RESULTS: Crude peptic ulcer
      recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric,
      duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively.
      Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5%
      and 1.3%, respectively. The recurrence rate was significantly higher in gastric
      ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs
      were significantly higher in those with gastric ulcer recurrence compared to
      duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at
      the same or adjacent sites as the previous ulcers). CONCLUSIONS: Curative
      treatment of H. pylori infection is useful in preventing ulcer recurrence.
      Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer
      tended to recur at the site of the original ulcers.

PMID- 15156900
TI  - False negative urea breath tests with H2-receptor antagonists: interactions
      between Helicobacter pylori density and pH.
AB  - BACKGROUND: We studied the effects of famotidine, sodium bicarbonate, and citric
      acid on the 13C-urea breath test (UBT). METHODS: Helicobacter pylori-infected
      volunteers received a UBT, 40 mg of famotidine at bedtime, and a second UBT
      (pudding test meal, 648 mg NaHCO3 tablet then 125 mg of urea in 200 ml of water
      containing 650 mg of NaHCO3). Experiment 2 consisted of four UBTs. Two were
      standard citric acid UBTs with 75 mg of urea and 2 g citric acid and two were
      sequential bicarbonate-citric acid UBTs. Sequential UBTs consisted of
      administration of a 648 mg bicarbonate tablet with 50 g of Polycose in 200 ml of
      water. Five minutes later, 125 mg of 13C-urea was given in 75 ml of water
      containing 650 mg of NaHCO3. Breath samples were collected after 15 minutes.
      Then, to acutely acidify the stomach, 4 g of citric acid was given in 200 ml of
      water. A second breath sample was collected 15 minutes after the citric acid. The
      standard UBTs were done before and after 6 days of famotidine (40 mg b.i.d.).
      Sequential UBTs were done after 1 and 6 days of famotidine therapy. Gastric
      biopsies for histology, culture, and mucosal cytokines were assessed before and
      after 6 days of famotidine. RESULTS: Eighteen subjects participated, 10 in each
      experiment; seven had endoscopy with biopsy. Famotidine/ bicarbonate resulted an
      approximately 50% fall in UBT values (p = .021) with 10% becoming negative. The
      gastric pH increased from 5.1 +/- 0.5 to 6.7 +/- 0.2 (p = .03) although no pH
      value predicted the occurrence of false negative results. Under famotidine acid
      suppression, NaHCO3 reduced the delta over baseline (DOB) by 63% (p = .021). This
      was reversed with citric acid. Histology showed a H2-receptor antagonist
      associated increase in the depth of gastric corpus inflammation. CONCLUSIONS: H2
      receptor antagonists differ from proton pump inhibitors as high intragastric pH
      may cause a reduction in urease activity, unrelated to a reduced bacterial load
      and reversed by citric acid.

PMID- 15156901
TI  - The TETRA study: a prospective evaluation of Helicobacter pylori 'test-and-treat'
      strategy on 736 patients in clinical practice.
AB  - AIMS: To prospectively evaluate the effectiveness of the test-and-treat strategy
      in a large group of dyspeptic patients in clinical practice. METHODS: Patients
      with ulcer-like dyspepsia, < 45 years, without alarm symptoms, were prospectively
      studied. Helicobacter pylori infection was diagnosed with the 13C-urea-breath
      test, and eradication or symptomatic treatment was prescribed accordingly.
      'Symptomatic improvement' was defined as the percentage of patients with a
      decrease of > or = 2 levels in the dyspepsia-severity-score or with no symptoms
      after treatment. Health status and use of health resources were also assessed.
      Endoscopy was performed in therapeutic failures. RESULTS: Out of 736 patients
      initially included, 422 received eradication, and 314 symptomatic therapy; 87%
      returned at 6 weeks and 67% at 6 months. At 6 months, 'symptomatic improvement'
      was achieved in 73% and 54% of the patients, in eradication and symptomatic
      groups, respectively (p < .001), and overall in 66%. A reduction of 78% in mean
      self-assessment visual analogical score was observed at 6 months. More than 50%
      of patients were 'much better' at control visits. Endoscopy (18%) and physician's
      visits (13%) were the main health resources used. No gastric or oesophageal
      cancer was diagnosed. CONCLUSION: This large prospective study shows that the
      test-and-treat strategy is effective and safe for management of dyspeptic
      patients in clinical practice.

PMID- 15156902
TI  - 13C-urea breath test to diagnose Helicobacter pylori infection in children aged
      up to 6 years.
AB  - BACKGROUND: 13C-urea breath test (13C-UBT) is an accurate noninvasive tool for
      diagnosis of Helicobacter pylori infection. It is considered the best method for
      epidemiological studies, but there are few studies to evaluate the 13C-UBT in
      infants and toddlers. AIM: To evaluate the 13C-UBT performed with infrared
      spectroscopy in children aged up to 6 years. PATIENTS: Sixty-eight patients (6
      months. to 5 years 11 months.) were evaluated prospectively and consecutively.
      METHODS: Helicobacter pylori infection was detected by positive culture, or rapid
      urease test and histological examination, both positive. 13C-UBT was performed
      with 50 mg of 13C-urea diluted in 100 ml of commercial orange juice. Two expired
      air samples were collected: before and 30 minutes after tracer ingestion. Cutoff
      of delta over baseline (DOB) was 4.0 per thousand and urea hydrolysis rate 10
      microg/minute. RESULTS: Fifteen of 68 (22.1%) patients were H. pylori infected.
      Sensitivity was 93.3% (95% CI; 86.8%-99.7%) and specificity was 96.2% (95% CI;
      93.6%-98.8%), and these values were equal for DOB and urea hydrolysis rate.
      Negative DOB values in noninfected patients ranged from -1.5 per thousand to 2.6
      per thousand and positive DOB values ranged from 10.8 per thousand to 105.5 per
      thousand. There was no relationship between DOB values and age. Conclusion. 13C
      UBT performed with infrared spectroscopy proved to be a reliable and accurate
      noninvasive diagnostic tool for H. pylori infection detection in children aged up
      to 6 years. Results far from cutoff value can clearly distinguish positive from
      negative 13C-UBT results in children up to 6 years old.

PMID- 15156903
TI  - Helicobacter pylori associated antigastric autoantibodies: role in Sjogren's
      syndrome gastritis.
AB  - BACKGROUND: Previous studies have shown that Helicobacter pylori seroprevalence
      in Sjogren's syndrome is comparable with that of the general population. However,
      the origin of the chronic gastropathy associated with this syndrome and the role
      of local autoimmunity--possibly triggered by bacterial infection--in its
      pathogenesis remain unclear. MATERIALS AND METHODS: We initially determined the
      prevalence of IgG anti H. pylori in dyspeptic subjects with and without Sjogren's
      syndrome. In subsets of both groups we then determined anti CagA and human tissue
      tested anticanalicular/antifoveolar autoantibodies. We also compared activity,
      atrophy and Mucosa Associated Lymphoid Tissue (MALT) scores, as well as symptoms,
      before and after bacterial eradication. RESULTS: Prevalence of H. pylori in
      Sjogren's syndrome patients was similar to controls: 31/54 (57%) vs. 93/150
      (62%). Anti CagA prevalence was also similar in the two groups. Twenty weeks
      after H. pylori eradication, histological activity decreased in both groups,
      however, atrophy and MALT decreased significantly only in controls. Sixteen
      months after H. pylori eradication, 75% of Sjogren's syndrome patients still
      complained of dyspepsia compared with 13% of controls. Finally, antigastric
      autoantibodies were present in 29% of tested Sjogren's syndrome patients vs. 28%
      of controls. CONCLUSIONS: H. pylori infection was equally prevalent among
      dyspeptic Sjogren's syndrome patients and dyspeptic controls. Likewise, there
      were no differences regarding anti CagA prevalence or antigastric autoantibodies
      among the two groups. The persistence of symptoms as well as of the lymphocytic
      infiltration and atrophy after H. pylori eradication in Sjogren's syndrome may
      underlie the 'endogenous' and still unknown nature of the gastropathy in this
      condition.

PMID- 15156904
TI  - Genotypes of the Helicobacter pylori vacA signal sequence differ with age in
      Korea.
AB  - BACKGROUND: Studies on Helicobacter pylori genotypes have focused on adults in
      developed countries, and data on the genotypes of Helicobacter pylori recovered
      from the children are rare. MATERIALS AND METHODS: One hundred and twenty-eight
      biopsy samples from patients with H. pylori infection were studied. The patients'
      ages ranged from 9 to 83 years. PCR analysis for vacA genotypes was performed
      using DNA extracted from biopsy specimens. RESULTS: Genotyping of the s-region
      showed s1a in 33 (25.8%) samples and s1c in 82 (64.1%) samples. When the
      specimens were grouped by age, the distribution of s-region genotype was found to
      be significantly different between groups (p = .002). The prevalence of s1a was
      45.2% in patients < 20 years old, but 14.9% in patients > or = 50 years old. On
      the other hand, the prevalence of s1c or recombinant s1a-s1c was higher in those
      > or = 50 years old. The distribution of the m-region did not differ
      significantly with age (p = .110). CONCLUSIONS: Strain populations infecting
      Korean adults and children differ.

PMID- 15156905
TI  - The incidence of Helicobacter pylori acquisition in children of a Canadian First
      Nations community and the potential for parent-to-child transmission.
AB  - BACKGROUND AND AIMS: We have previously reported that Wasagamack, a Canadian
      First Nations community has a seroprevalence rate of Helicobacter pylori of 95%
      and a prevalence rate among children aged 0-12 years as measured by stool antigen
      testing of 56%. We aimed to determine the rate of infection acquisition and
      possible modes of transmission of childhood Helicobacter pylori infection in this
      Canadian First Nations community. METHODS: Children who were previously negative
      for H. pylori by stool antigen testing in August 1999 were eligible for
      enrollment in August 2000; 50 (77%) eligible children underwent stool collection.
      H. pylori stool antigen status was tested using the Premier Platinum HpSA test.
      Drinking water samples, maternal saliva, breast milk, local berries and flies
      were tested by three complementary H. pylori-specific PCR assays. Soothers or
      bottle nipples, collected from 16 children whose H. pylori stool antigen status
      was determined, were bathed in sterile water and this water was tested by PCR.
      RESULTS: Stool was positive for H. pylori in 16% (8/ 50) of children retested.
      Five had no other siblings infected and three had infected siblings. The mothers
      of all children infected were positive for H. pylori. The median age of newly
      infected children was 6 years (range 1-13 years). By PCR, 78% (18/23) mothers'
      saliva samples, 69% (11/16) soother water samples and 9% (1/11) water samples
      from infected homes tested positive. All of 24 sequenced PCR-produced DNA
      fragments from samples showed 99% homology with that from ATCC type strain H.
      pylori. CONCLUSIONS: The rate of childhood H. pylori acquisition was 16% over 1
      year, and was not dependent on number of siblings infected. The finding of
      homologous H. pylori DNA in saliva and in soother water suggests the possibility
      of human to human transmission, particularly via an oral-oral route. Thus, there
      is the potential for further investigations in this population and other endemic
      communities that are directed at prevention of infection transmission via this
      modality.

PMID- 15156906
TI  - Evaluation of stool antigen test, PCR on ORAL samples and serology for the
      noninvasive detection of Helicobacter pylori infection in children.
AB  - BACKGROUND: Endoscopy represents the gold standard for the diagnosis of
      Helicobacter pylori infection. We evaluated three noninvasive tests in a group of
      children: the immunoassay for detection of H. pylori stool antigen, the
      polimerase chain reaction for identification of bacterial DNA on the oral cavity
      and the serum specific antibodies. MATERIALS AND METHODS: One hundred and ninety
      children underwent endoscopy for various gastrointestinal symptoms. H. pylori
      stool antigen and anti-H. pylori antibodies were assayed by commercial kits. The
      bacterial DNA on saliva and oral plaque was detected by a seminested PCR.
      RESULTS: Based on the positivity of culture or urease rapid test and histology,
      infection was detected in 47 patients. The statistical analysis showed that, for
      the detection of the infection, stool antigen assay is more effective in
      sensitivity and negative predictive value (91.5% and 96.5%), whereas specificity
      and positive predictive values appear slightly better in serology (89.6% and
      76.0%). Correlations between serum IgG both with patients' age (r = 0.21, p <
      .05) and H. pylori stool antigen (r = 0.47, p < .01) were found. The search for
      bacterial DNA on oral samples proved to be very specific (99.1% on saliva and
      98.2% on plaque), but insensitive (22.2% and 25.7%). CONCLUSIONS. In children H.
      pylori stool antigen represents a sensitive test, suitable for detecting H.
      pylori infection. Serum IgG proved to be more specific; the PCR on the oral
      cavity resulted as being a very specific, but insensitive test.

PMID- 15156907
TI  - The prevalence and incidence of Helicobacter pylori infections among young
      recruits during service in the Hungarian Army.
AB  - BACKGROUND: A vast number of data indicate that the prevalence of Helicobacter
      pylori infections is positively correlated with age and is different in various
      countries. Although our knowledge of transmission of H. pylori is very limited,
      it is reasonable to assume that it could be much more contagious in closed
      communities, for example in garrisons, than in normal populations. METHODS: Young
      male recruits (aged 19-23 years) in the Hungarian Army were tested for
      seropositivity at the beginning and at the end of their military service.
      RESULTS: The prevalence of H. pylori seropositivity was found to be 23% (*CI95%:
      21-24%) among the young male recruits. Seroconversion among the formerly
      seronegative persons after completing either their 9-month or 6-month military
      service was 30% (CI95%: 25-35%) and 23% (CI95%: 8-45%), respectively. In those
      groups, where either the H. pylori infection was eradicated by antibiotics or
      hygienic countermeasures were introduced, the infection rate was reduced from 23%
      to 11% (CI95%: 3-25%) and to 0% (CI95%: 0-6%); p > .2 and p < .002, respectively.
      CONCLUSION: Our data suggest that, although H. pylori has a very high
      contagiosity in closed communities, its spread can be reduced or even prevented
      by medication of the infected persons and/or by improving the hygienic conditions
      and introducing anti-infective sanitary regulations.

PMID- 15156908
TI  - Serological responses of FldA and small-molecular-weight proteins of Helicobacter
      pylori: correlation with the presence of the gastric MALT tissue.
AB  - PURPOSE: We tested whether the serological response to Flavodoxin-A (FldA)
      protein and anti-Helicobacter pylori immunoblots correlated to the degree of
      mucosaassociated lymphoid tissue (MALT) in the stomach. METHODS: Eighty H. pyloni
      infected patients with different degrees of MALT in the stomach were investigated
      with serum sampling and endoscopy on enrolment, the 2nd and the 12th months after
      anti-H. pylori therapy. All sera were tested for the anti-FldA protein and anti
      H. pylon immunoblots, including 19.5, 26.5, 30, 35, 89, and 116 KDa (CagA).
      Regression of follicular gastritis was assessed by histology. RESULTS: Patients
      with dense lymphoid follicles had higher prevalence rates of anti-FldA protein,
      19.5, 26.5, and 30 KDa antibodies of H. pylori (p < .05). Histologic downgrade of
      MALT was observed in 25% (10/40) of patients in the 2nd month and in 60% (23/38)
      in the 12th month after H. pylori therapy. After H. pylori eradication, the
      patients with MALT and dense lymphoid follicles had significantly negative
      seroconversions of 19.5, 26.5, 30, and 35 KDa antibodies (p < .05), but not of
      CagA and FldA. CONCLUSION: Patients with gastric MALT and dense lymphoid
      follicles had different anti-H. pylori serological responses to those with scanty
      or an absence of lymphoid follicles. The negative seroconversion of the smaller
      molecular-weight proteins, but not CagA and FldA, may correlate with the
      regression of MALT by H. pylori eradication.

PMID- 15156909
TI  - Pharmacoeconomics of gastrointestinal drug utilisation prior and post
      Helicobacter pylori eradication.
AB  - BACKGROUND: Eradication of Helicobacter pylori prevents recurrence of peptic
      ulcer. In pharmacoeconomic analyses it is often presumed that after successful
      eradication no more gastrointestinal drugs are used. We investigated this
      presumed positive monetary effect using General Practitioners prescribing data,
      including information in diagnosis. METHODS: From the RNG-database we identified
      patients with a H. pylori eradication in the years 1997-2000. H. pylori
      eradication was defined as a prescription of two antibiotics and one
      gastrointestinal drug on the same day. Patients were divided into a group with
      diagnosed ulcers and a group without diagnosed ulcers. Gastrointestinal drug
      costs were calculated for 4 months prior to eradication and 9-12 months post
      eradication. For comparison costs in all periods were expressed per patient per
      period. For statistical analysis the paired t-test was used. RESULTS: One hundred
      and two patients were eligible for evaluation. Of these patients 35 had a
      diagnosed ulcer and 67 had not. Generally the number of patients on
      gastrointestinal drugs decreased (61% prior vs. 33% post), however, the drug
      costs did not change (Euro 33 prior vs. Euro 34 post). Costs for proton pump
      inhibitors increased post eradication (Euro 14 prior vs. Euro 28 post). The ulcer
      and nonulcer group showed similar results. CONCLUSION: Helicobacter pylori
      eradication is thought to be cost effective, however, we did not find a decrease
      in costs for all gastrointestinal drugs. There may be a great pharmacoeconomical
      advantage when it is possible to predict which patients are more likely to 'fail'
      eradication therapy.

PMID- 15156910
TI  - Early epigastric pain after PPI administration: exacerbation of Helicobacter
      pylori corpus gastritis?

PMID- 15156911
TI  - Explaining phenotypic selection on plant attractive characters: male function,
      gender balance or ecological context?
AB  - It is widely agreed that the flowers of hermaphrodite plants evolve in response
      to selection acting simultaneously through male and female sexual functions, but
      we know very little about the pattern of gender-specific selection. We review
      three current hypotheses for gender-specific selection by viewing them within a
      single phenotypic selection framework. We compile data from phenotypic selection
      and manipulative studies and evaluate the fit between empirical data and the
      hypotheses. In this preliminary analysis, we find that neither the male-function
      hypothesis nor the gender-balance hypothesis is well supported. However, the
      context-dependence hypothesis is supported by the documented diversity of gender
      specific selection and by evidence that selection through female fertility is
      significantly correlated with pollen limitation of seed production. Future
      studies contributing to our understanding of selection through male and female
      function in plants need to quantify and manipulate the ecological context for
      reproduction, as well as describe male and female fitness responses to fine-scale
      trait manipulation.

PMID- 15156912
TI  - The role of subspecies in obscuring avian biological diversity and misleading
      conservation policy.
AB  - Subspecies are often used in ways that require their evolutionary independence,
      for example as proxies for units of conservation. Mitochondrial DNA sequence data
      reveal that 97% of continentally distributed avian subspecies lack the population
      genetic structure indicative of a distinct evolutionary unit. Subspecies
      considered threatened or endangered, some of which have been targets of expensive
      restoration efforts, also generally lack genetic distinctiveness. Although
      sequence data show that species include 1.9 historically significant units on
      average, these units are not reflected by current subspecies nomenclature. Yet,
      it is these unnamed units and not named subspecies that should play a major role
      in guiding conservation efforts and in identifying biological diversity. Thus, a
      massive reorganization of classifications is required so that the lowest ranks,
      be they species or subspecies, reflect evolutionary diversity. Until such
      reorganization is accomplished, the subspecies rank will continue to hinder
      progress in taxonomy, evolutionary studies and especially conservation.

PMID- 15156913
TI  - Diversity and population structure of a near-shore marine-sediment viral
      community.
AB  - Viruses, most of which are phage, are extremely abundant in marine sediments, yet
      almost nothing is known about their identity or diversity. We present the
      metagenomic analysis of an uncultured near-shore marine-sediment viral community.
      Three-quarters of the sequences in the sample were not related to anything
      previously reported. Among the sequences that could be identified, the majority
      belonged to double-stranded DNA phage. Temperate phage were more common than
      lytic phage, suggesting that lysogeny may be an important lifestyle for sediment
      viruses. Comparisons between the sediment sample and previously sequenced
      seawater viral communities showed that certain phage phylogenetic groups were
      abundant in all marine viral communities, while other phage groups were under
      represented or absent. This 'marineness' suggests that marine phage are derived
      from a common set of ancestors. Several independent mathematical models, based on
      the distribution of overlapping shotgun sequence fragments from the library, were
      used to show that the diversity of the viral community was extremely high, with
      at least 10(4) viral genotypes per kilogram of sediment and a Shannon index
      greater than 9 nats. Based on these observations we propose that marine-sediment
      viral communities are one of the largest unexplored reservoirs of sequence space
      on the planet.

PMID- 15156914
TI  - Global hot spots of biological invasions: evaluating options for ballast-water
      management.
AB  - Biological invasions from ballast water are a severe environmental threat and
      exceedingly costly to society. We identify global hot spots of invasion based on
      worldwide patterns of ship traffic. We then estimate the rate of port-to-port
      invasion using gravity models for spatial interactions, and we identify
      bottlenecks to the regional exchange of species using the Ford-Fulkerson
      algorithm for network flows. Finally, using stochastic simulations of different
      strategies for controlling ballast-water introductions, we find that reducing the
      per-ship-visit chance of causing invasion is more effective in reducing the rate
      of biotic homogenization than eliminating key ports that are the epicentres for
      global spread.

PMID- 15156915
TI  - Wavelength-selective and anisotropic light-diffusing scale on the wing of the
      Morpho butterfly.
AB  - We have found that cover scales on the wing of the butterfly Morpho didius
      possess specially designed microscopic structures for wavelength-selective
      reflection and contribute considerably to the brilliant blue colour of the wing.
      In addition, the cover scale functions as an anisotropic optical diffuser which
      diffuses light only in one plane, while it makes the range of reflection narrower
      in the orthogonal plane. The quantitative analyses for the wavelength-selection
      mechanism and the peculiar optical diffuser are given and the role of such a
      special optical effect is discussed from physical and biological viewpoints.

PMID- 15156916
TI  - The aerodynamic costs of warning signals in palatable mimetic butterflies and
      their distasteful models.
AB  - Bates hypothesized that some butterfly species that are palatable gain protection
      from predation by appearing similar to distasteful butterflies. When undisturbed,
      distasteful butterflies fly slowly and in a straight line, and palatable Batesian
      mimics also adopt this nonchalant behaviour. When seized by predators,
      distasteful butterflies are defended by toxic or nauseous chemicals. Lacking
      chemical defences, Batesian mimics depend on flight to escape attacks. Here, I
      demonstrate that flight in warning-coloured mimetic butterflies and their
      distasteful models is more costly than in closely related non-mimetic
      butterflies. The increased cost is the result of differences in both wing shape
      and kinematics. Batesian mimics and their models slow the angular velocity of
      their wings to enhance the colour signal but at an aerodynamic cost. Moreover,
      the design for flight in Batesian mimics has an additional energetic cost over
      that of its models. The added cost may cause Batesian mimics to be rare,
      explaining a general pattern that Bates first observed.

PMID- 15156917
TI  - Remarkable iridescence in the hindwings of the damselfly Neurobasis chinensis
      chinensis (Linnaeus) (Zygoptera: Calopterygidae).
AB  - The bright green dorsal iridescence of the hindwings of Neurobasis chinensis
      chinensis males, very rare in Odonata, is known to play a significant role in
      their courtship behaviour. The mechanism responsible for such high contrast and
      spectrally pure colour has been investigated and found to be optical
      interference, producing structural colour from distinct laminations in the wing
      membrane cuticle. The ventral sides of these iridescent wings are dark brown in
      colour. In a single continuous membrane of wing cuticle, this is an effect that
      requires a specialized structure. It is accomplished through the presence of high
      optical absorption (kappa = 0.13) within two thick layers near the ventral
      surface of the wing, which leads to superior dorsal colour characteristics. By
      simultaneously fitting five sets of optical reflectivity and transmissivity
      spectra to theory, we were able to extract very accurate values of the complex
      refractive index for all three layer types present in the wing. The real parts of
      these are n = 1.47, 1.68 and 1.74. Although there is often similarly significant
      dorsal and ventral colour contrast in other structurally coloured natural
      systems, very few system designs comprise only a single continuous membrane.

PMID- 15156918
TI  - Floral symmetry affects speciation rates in angiosperms.
AB  - Despite much recent activity in the field of pollination biology, the extent to
      which animal pollinators drive the formation of new angiosperm species remains
      unresolved. One problem has been identifying floral adaptations that promote
      reproductive isolation. The evolution of a bilaterally symmetrical corolla
      restricts the direction of approach and movement of pollinators on and between
      flowers. Restricting pollinators to approaching a flower from a single direction
      facilitates specific placement of pollen on the pollinator. When coupled with
      pollinator constancy, precise pollen placement can increase the probability that
      pollen grains reach a compatible stigma. This has the potential to generate
      reproductive isolation between species, because mutations that cause changes in
      the placement of pollen on the pollinator may decrease gene flow between
      incipient species. I predict that animal-pollinated lineages that possess
      bilaterally symmetrical flowers should have higher speciation rates than lineages
      possessing radially symmetrical flowers. Using sister-group comparisons I
      demonstrate that bilaterally symmetric lineages tend to be more species rich than
      their radially symmetrical sister lineages. This study supports an important role
      for pollinator-mediated speciation and demonstrates that floral morphology plays
      a key role in angiosperm speciation.

PMID- 15156919
TI  - Activation-threshold tuning in an affinity model for the T-cell repertoire.
AB  - Naive T cells respond to peptides from foreign proteins and remain tolerant to
      self peptides from endogenous proteins. It has been suggested that self tolerance
      comes about by a 'tuning' mechanism, i.e. by increasing the T-cell activation
      threshold upon interaction with self peptides. Here, we explore how such an
      adaptive mechanism of T-cell tolerance would influence the reactivity of the T
      cell repertoire to foreign peptides. We develop a computer simulation model in
      which T cells are tolerized by increasing their activation-threshold dependent on
      the affinity with which they see self peptides presented in the thymus. Thus,
      different T cells acquire different activation thresholds (i.e. different cross
      reactivities). In previous mathematical models, T-cell tolerance was deletional
      and based on a fixed cross-reactivity parameter, which was assumed to have
      evolved to an optimal value. Comparing these two different tolerance-induction
      mechanisms, we found that the tuning model performs somewhat better than an
      optimized deletion model in terms of the reactivity to foreign antigens. Thus,
      evolutionary optimization of clonal cross-reactivity is not required. A
      straightforward extension of the tuning model is to delete T-cell clones that
      obtain a too high activation threshold, and to replace these by new clones. The
      reactivity of the immune repertoires of such a replacement model is enchanced
      compared with the basic tuning model. These results demonstrate that activation
      threshold tuning is a functional mechanism for self tolerance induction.

PMID- 15156920
TI  - The reinfection threshold promotes variability in tuberculosis epidemiology and
      vaccine efficacy.
AB  - Population patterns of infection are determined largely by susceptibility to
      infection. Infection and vaccination induce an immune response that, typically,
      reduces susceptibility to subsequent infections. With a general epidemic model,
      we detect a 'reinfection threshold', above which reinfection is the principal
      type of transmission and, consequently, infection levels are much higher and
      vaccination fails. The model is further developed to address human tuberculosis
      (TB) and the impact of vaccination. The bacille Calmette-Guerin (BCG) is the only
      vaccine in current use against TB, and there is no consensus about its
      usefulness. Estimates of protection range from 0 to 80%, and this variability is
      aggravated by an association between low vaccine efficacy and high prevalence of
      the disease. We propose an explanation based on three postulates: (i) the
      potential for transmission varies between populations, owing to differences in
      socio-economic and environmental factors; (ii) exposure to mycobacteria induces
      an immune response that is partially protective against reinfection; and (iii)
      this protection is not significantly improved by BCG vaccination. These
      postulates combine to reproduce the observed trends, and this is attributed to a
      reinfection threshold intrinsic to the transmission dynamics. Finally, we
      demonstrate how reinfection thresholds can be manipulated by vaccination
      programmes, suggesting that they have a potentially powerful role in global
      control.

PMID- 15156921
TI  - Frequency-dependent incidence in models of sexually transmitted diseases:
      portrayal of pair-based transmission and effects of illness on contact behaviour.
AB  - We explore the transmission process for sexually transmitted diseases (STDs). We
      derive the classical frequency-dependent incidence mechanistically from a pair
      formation model, using an approximation that applies to populations with rapid
      pairing dynamics (such as core groups or non-pair-bonding animals). This
      mechanistic derivation provides a framework to assess how accurately frequency
      dependent incidence portrays the pair-based transmission known to underlie STD
      dynamics. This accuracy depends strongly on the disease being studied: frequency
      dependent formulations are more suitable for chronic less-transmissible
      infections than for transient highly transmissible infections. Our results thus
      support earlier proposals to divide STDs into these two functional classes, and
      we suggest guidelines to help assess under what conditions each class can be
      appropriately modelled using frequency-dependent incidence. We then extend the
      derivation to include situations where infected individuals exhibit altered
      pairing behaviour. For four cases of increasing behavioural complexity, analytic
      expressions are presented for the generalized frequency-dependent incidence rate,
      basic reproductive number (R0) and steady-state prevalence (i infinity) of an
      epidemic. The expression for R0 is identical for all cases, giving refined
      insights into determinants of invasibility of STDs. Potentially significant
      effects of infection-induced changes in contact behaviour are illustrated by
      simulating epidemics of bacterial and viral STDs. We discuss the application of
      our results to STDs (in humans and animals) and other infectious diseases.

PMID- 15156922
TI  - Concordant preferences for opposite-sex signals? Human pheromones and facial
      characteristics.
AB  - We have investigated whether preferences for masculine and feminine
      characteristics are correlated across two modalities, olfaction and vision. In
      study 1, subjects rated the pleasantness of putative male (4,16-androstadien-3
      one; 5alpha-androst-16-en-3-one) and female (1,3,5 (10),16-estratetraen-3-ol)
      pheromones, and chose the most attractive face shape from a masculine-feminine
      continuum for a long- and a short-term relationship. Study 2 replicated study 1
      and further explored the effects of relationship context on pheromone ratings.
      For long-term relationships, women's preferences for masculine face shapes
      correlated with ratings of 4,16-androstadien-3-one and men's preferences for
      feminine face shapes correlated with ratings of 1,3,5(10),16-estratetraen-3-ol.
      These studies link sex-specific preferences for putative human sex pheromones and
      sexually dimorphic facial characteristics. Our findings suggest that putative sex
      pheromones and sexually dimorphic facial characteristics convey common
      information about the quality of potential mates.

PMID- 15156923
TI  - Genetic sex determination, gender identification and pseudohermaphroditism in the
      knobbed whelk, Busycon carica (Mollusca: Melongenidae).
AB  - We report perhaps the first genic-level molecular documentation of a mammalian
      like 'X-linked' mode of sex determination in molluscs. From family inheritance
      data and observed associations between sex-phenotyped adults and genotypes in
      Busycon carica, we deduce that a polymorphic microsatellite locus (bc2.2) is
      diploid and usually heterozygous in females, hemizygous in males, and that its
      alleles are transmitted from mothers to sons and daughters but from fathers to
      daughters only. We also employ bc2.2 to estimate near-conception sex ratio in
      whelk embryos, where gender is indeterminable by visual inspection. Statistical
      corrections are suggested at both family and population levels to accommodate the
      presence of homozygous bc2.2 females that could otherwise be genetically mistaken
      for hemizygous males. Knobbed whelks were thought to be sequential
      hermaphrodites, but our evidence for genetic dioecy supports an earlier
      hypothesis that whelks are pseudohermaphroditic (falsely appear to switch
      functional sex when environmental conditions induce changes in sexual phenotype).
      These findings highlight the distinction between gender in a genetic versus
      phenotypic sense.

PMID- 15156924
TI  - 'Optimal' vortex rings and aquatic propulsion mechanisms.
AB  - Fishes swim by flapping their tail and other fins. Other sea creatures, such as
      squid and salps, eject fluid intermittently as a jet. We discuss the fluid
      mechanics behind these propulsion mechanisms and show that these animals produce
      optimal vortex rings, which give the maximum thrust for a given energy input. We
      show that fishes optimize both their steady swimming efficiency and their ability
      to accelerate and turn by producing an individual optimal ring with each flap of
      the tail or fin. Salps produce vortex rings directly by ejecting a volume of
      fluid through a rear orifice, and these are also optimal. An important
      implication of this paper is that the repetition of vortex production is not
      necessary for an individual vortex to have the 'optimal' characteristics.

PMID- 15156926
TI  - Hepatitis B: a comprehensive prevention, diagnosis, and treatment program--past,
      present, and future.

PMID- 15156925
TI  - Regional climatic warming drives long-term community changes of British marine
      fish.
AB  - Climatic change has been implicated as the cause of abundance fluctuations in
      marine fish populations worldwide, but the effects on whole communities are
      poorly understood. We examined the effects of regional climatic change on two
      fish assemblages using independent datasets from inshore marine (English Channel,
      1913-2002) and estuarine environments (Bristol Channel, 1981-2001). Our results
      show that climatic change has had dramatic effects on community composition. Each
      assemblage contained a subset of dominant species whose abundances were strongly
      linked to annual mean sea-surface temperature. Species' latitudinal ranges were
      not good predictors of species-level responses, however, and the same species did
      not show congruent trends between sites. This suggests that within a region,
      populations of the same species may respond differently to climatic change,
      possibly owing to additional local environmental determinants, interspecific
      ecological interactions and dispersal capacity. This will make species-level
      responses difficult to predict within geographically differentiated communities.

PMID- 15156927
TI  - Therapeutic advances in chronic hepatitis B.
AB  - In conclusion, most patients with CHB have their disease controlled by lamivudine
      therapy, and those with elevated ALT respond well. The incidence of YMDD-variant
      increases with duration of treatment, although patients with YMDD still gain
      clinical benefit from continued lamivudine therapy and seroconversion can still
      be achieved. Lamivudine has shown efficacy in HBeAg-negative patients and those
      with decompensated cirrhosis. In long-term use, lamivudine has been found to be
      well tolerated. Even in patients with YMDD-variant HBV, no increase in hepatic
      serious adverse events was seen. In patients with decompensated CHB the
      combination of lamivudine and adefovir dipivoxil showed significant efficacy.
      After only 24 weeks, clinical improvements in liver function were seen.

PMID- 15156928
TI  - Review of economic benefits of treating chronic hepatitis B with lamivudine.

PMID- 15156929
TI  - Hepatitis disease management programs in Malaysia.
AB  - The MLF since its inception in 1996 has endeavored to develop a coordinated
      approach towards the improved care and treatment of liver diseases in Malaysia.
      Its close liaison with the Malaysian MOH, local medical associations, and
      corporate bodies has contributed to the success of its many programs. Educating
      the public, research, and training have been important elements of successful
      hepatitis disease control programs. Hepatitis Days have been proven to be very
      successful in raising the awareness of the general public to hepatitis disease.
      Rapid screening and vaccination has also helped to remove the social stigma
      associated with the disease, eliminated the need for numerous clinic
      appointments, and rendered vaccination more accessible to the public. The MLF
      perspective emphasizes the need for collaborative effort between Government
      bodies and other agencies, such as non-governmental organizations, laboratories,
      and the medical fraternity, to ensure the overall success of hepatitis disease
      management programs.

PMID- 15156930
TI  - The importance and benefits of hepatitis A prevention in chronic liver disease
      patients.

PMID- 15156931
TI  - Shoulder pain in chronic spinal cord injury, Part I: Epidemiology, etiology, and
      pathomechanics.
AB  - STUDY DESIGN: Review of the literature. BACKGROUND/OBJECTIVE: Shoulder pain is
      extremely common in individuals with chronic spinal cord injury (SCI) and is a
      source of morbidity and functional loss. The purpose of this review is to outline
      the present knowledge of the epidemiology, etiology, and pathomechanics of
      musculoskeletal shoulder pain in individuals with chronic SCI. METHODS: Review of
      the literature using PubMed/MEDLINE, EMBASE, and bibliographies of selected
      articles. RESULTS: Shoulder pain is more common in individuals with tetraplegia
      and complete injuries and may occur more frequently in women. Musculoskeletal
      conditions, primarily injuries to the rotator cuff, are most common. Risk factors
      include the duration of injury, older age, higher body mass index, the use of a
      manual wheelchair, poor seated posture, decreased flexibility, and muscle
      imbalances in the rotator cuff and scapular stabilizing muscles. CONCLUSION: With
      a better understanding of the epidemiology, etiology, and basic pathomechanics of
      shoulder pain in SCI, physicians are in a better position to evaluate, treat, and
      prevent these disorders.

PMID- 15156932
TI  - The relationship of spinal cord injury trauma to alcohol misuse: a study of
      monozygotic twins.
AB  - BACKGROUND: Substance misuse frequently is correlated with serious trauma such as
      spinal cord injury (SCI). Two hypotheses to this effect are (a) substance abuse
      predates injury and is a risk factor or trigger for serious injury such as SCI;
      or (b)substance abuse begins postinjury, and alcohol or other drugs are used to
      ameliorate the physical and emotional distress that result from SCI. METHODS: To
      test these two hypotheses, 1 4 pairs of monozygotic twins, in which 1 of each
      pair had sustained an SCI, were studied. The twin without SCI was used as a
      control for preinjury substance misuse status for the twin with SCI. RESULTS: No
      significant differences between SCI and non-SCI co-twins' substance use patterns
      were found. CONCLUSION: These findings suggest that drinking patterns might not
      be significantly affected by SCI and that substance misuse might precede injury.

PMID- 15156933
TI  - Treatment of major depression in individuals with spinal cord injury.
AB  - OBJECTIVE: This study evaluated the effects of treating major depression in
      individuals with spinal cord injury (SCI), focusing on the degree of improvement
      and correlated changes that could be expected in 6 months of treatment. DESIGN: A
      pretreatment-posttreatment design was used. Random assignment to a nontreatment
      group could not be implemented ethically. Therefore, this study compared
      participants who declined treatment to persons who accepted treatment over a 24
      month period. SETTING AND PARTICIPANTS: Participants were outpatients of a large
      urban rehabilitation center in southern California. Twenty-eight participants who
      accepted treatment were assigned to a treatment group; 15 individuals who
      declined treatment were assigned to a nontreatment group. The age of the
      participants ranged from 20 to 74 years. Varying levels of SCI dysfunction were
      represented. INTERVENTIONS: A 6-month combination of psychotherapy and
      antidepressant medication. OUTCOME MEASURES: A depression inventory, a community
      activities checklist, and a life satisfaction scale. RESULTS: A significant (P <
      0.001) 57% reduction in depressive symptoms occurred in the treatment group,
      whereas there was no significant change in the nontreatment group. At the end of
      6 months, 30% of participants had no depression, 42% had minor depression, and
      29% still had major depression, but to a lesser degree. Community activities
      increased significantly over the treatment period, as did life satisfaction.
      CONCLUSION: The results suggest that depression is treatable in this population,
      although 6 months may not be sufficient to reach maximum benefit in all cases.
      This study further identified obstacles that limited the ability to randomize
      participants into treatment arms and made it difficult to deliver services to all
      those in need. Complications related to SCI, such as difficulties in
      transportation, likely restrict the ability to implement needed services to many
      individuals with SCI.

PMID- 15156934
TI  - Evaluation of cranberry supplement for reduction of urinary tract infections in
      individuals with neurogenic bladders secondary to spinal cord injury. A
      prospective, double-blinded, placebo-controlled, crossover study.
AB  - OBJECTIVE: To determine the effectiveness of cranberry supplement at preventing
      urinary tract infections (UTIs) in persons with spinal cord injury (SCI). DESIGN:
      A prospective, double-blinded, placebo-controlled, crossover study. PARTICIPANTS:
      21 individuals with neurogenic bladders secondary to SCI. MAIN OUTCOME MEASURES:
      Favorable or unfavorable response of cranberry supplement vs placebo on urinary
      bacterial counts and white blood cell (WBC) counts and the combination of
      bacterial and WBC counts. METHODS: Individuals with neurogenic bladders due to
      SCI were recruited and randomly assigned to standardized 400-mg cranberry tablets
      or placebo 3 times a day for 4 weeks. After 4 weeks and an additional 1-week
      "washout period," participants were crossed over to the other group. Participants
      were seen weekly, during which a urine analysis was obtained. UTI was defined as
      significant bacterial or yeast colony counts in the urine and elevated WBC counts
      (WBC count > or = 10 per high power field) in centrifuged urine. Participants
      with symptomatic infections were treated with appropriate antibiotics for 7 days
      and restarted on the cranberry tablet/ placebo after a 7-day washout period.
      Urinary pH between the cranberry and placebo groups was compared weekly. Data
      were analyzed using the Ezzet and Whitehead's random effect approach. RESULTS:
      There was no statistically significant treatment (favorable) effect for cranberry
      supplement beyond placebo when evaluating the 2 treatment groups for bacterial
      count, WBC count, or WBC and bacterial counts in combination. Urinary pH did not
      differ between the placebo and cranberry groups. CONCLUSION: Cranberry tablets
      were not found to be effective at changing urinary pH or reducing bacterial
      counts, urinary WBC counts, or UTIs in individuals with neurogenic bladders.
      Further long-term studies evaluating specific types of bladder management and
      UTIs will help to determine whether there is any role for the use of cranberries
      in individuals with neurogenic bladders.

PMID- 15156935
TI  - Effect of cranberry extract on bacteriuria and pyuria in persons with neurogenic
      bladder secondary to spinal cord injury.
AB  - OBJECTIVE: To determine whether antibacterial effects of cranberry extract will
      reduce or eliminate bacteriuria and pyuria in persons with spinal cord injury
      (SCI). DESIGN: Randomized, double-blind, placebo-controlled study. PARTICIPANTS:
      Participants were people with SCI residing in the community who were 1 year or
      longer postinjury with neurogenic bladder managed by intermittent catheterization
      or external collection device and a baseline urine culture demonstrating at least
      10(5) colonies per milliliter of bacteria. METHODS: Each participant ingested 2 g
      of concentrated cranberry juice or placebo in capsule form daily for 6 months.
      Baseline urinalysis and cultures were performed at the time of the initial clinic
      visit and monthly for 6 months. Microbiologic data were evaluated using analysis
      of variance with repeated measures. RESULTS: Twenty-six persons received
      cranberry extract and 22 persons received placebo. There were no differences or
      trends detected between participants and controls with respect to number of urine
      specimens with bacterial counts of at least 10(4) colonies per milliliter, types
      and numbers of different bacterial species, numbers of urinary leukocytes,
      urinary pH, or episodes of symptomatic urinary tract infection. CONCLUSION:
      Cranberry extract taken in capsule form did not reduce bacteriuria and pyuria in
      persons with SCI and cannot be recommended as a means to treat these conditions.

PMID- 15156936
TI  - Psychometric rigor of the Grasp and Release Test for measuring functional
      limitation of persons with tetraplegia: a preliminary analysis.
AB  - OBJECTIVE: The purpose of the study was to further develop the psychometric rigor
      of the Grasp and Release Test (GRT), a hand function assessment designed to
      measure tendon transfer and functional electrical stimulation (FES) outcomes on
      functional limitation of individuals with tetraplegia. METHODS: Nineteen
      participants (21 hands) between 7 and 20 years of age with cervical-level spinal
      cord injuries (SCIs) participated in this study. Three participants (5 hands) had
      strong C6 or C7 function and underwent bilateral surgical tendon transfers to
      restore volitional thumb and finger flexion. The remaining 16 participants (16
      hands) had C5- or weak C6-level SCI and underwent unilateral surgical
      implantation of the Freehand System for stimulated grasp and release. Preliminary
      evaluation of test-retest reliability, predictive validity, and sensitivity to
      change of the GRT was conducted. Reproducibility of test scores was evaluated by
      intraclass correlation coefficients (ICCs). RESULTS: Three objects-which included
      a fork, paperweight, and videotape-had perfect correlation. For the 3 remaining
      GRT objects, ICC values were significant (block = 0.87, peg = 0.93, can = 0.99; P
      < 0.01). For predictive validity, the relationships between 12-month Functional
      Independence Measure (FIM) scores and the peg, block, paperweight, and total
      number of GRT objects were nonsignificant. Correlation was significant between 12
      month FIM scores and the fork (rho = 0.624, P < 0.01), can (rho = 0.700, P <
      0.01), and videotape (rho = 0.503, P < 0.05). Sensitivity to change was evident
      by a significant difference between baseline and postrehabilitation GRT scores
      for the fork (z = 3.05, P < 0.01), paperweight (z = 2.83, P < 0.01), and can (z =
      2.66, P < 0.01), and between the total number of GRT objects that were
      manipulated following surgery as compared with the number prior to surgery (z =
      3.40, P < 0.05). CONCLUSION: Based on this study, the GRT has good test-retest
      reliability as evidenced by coefficients between 0.87 and 1.00, and is able to
      detect changes in hand function following tendon transfers and FES.

PMID- 15156937
TI  - Impact of a urinary tract infection educational program in persons with spinal
      cord injury.
AB  - OBJECTIVE: To test the hypotheses that an educational program reduces the
      frequency and severity of urinary tract infections (UTIs) in persons with spinal
      cord injury (SCI) and impacts health beliefs, locus of control, and self
      efficacy. DESIGN: Randomized controlled study. METHODS: Fifty-six participants
      were randomized to patient educational program or control groups after a 5- or 6
      month baseline period. The educational program group received written material on
      UTIs, a self-administered test, a review by nurse and physician, and a follow-up
      telephone call. Data were collected monthly throughout the baseline period and
      the 5- or 6-month follow-up period. OUTCOME MEASURE: The measures used were
      significant urine colony counts (UCCs), number of symptoms and UTIs, episodes of
      antibiotic treatment for UTIs, and 3 questionnaires (the Health Beliefs
      Questionnaire, the Multidimensional Health Locus of Control [MHLC] Scale, and a
      self-efficacy questionnaire). RESULTS: When controlling for baseline counts and
      the difference between groups at baseline, the treatment group had significantly
      fewer significant UCCs than did the control group (P = 0.009). A trend also was
      seen for fewer symptom reports (P = 0.094) and fewer number of antibiotic
      treatment episodes (P = 0.232) in the treatment group. In addition, whereas the
      treatment group tended to have higher scores on the internal MHLC Scale (P =
      0.066), they also perceived the severity of UTIs as greater than did the control
      group (P = 0.042) and had lower scores on the self-efficacy questionnaire (P =
      0.033). CONCLUSION: This is the first randomized controlled trial to demonstrate
      a significant reduction in bacterial load in the urine of persons with SCIs and
      an apparent reduction of symptoms and antibiotic treatment episodes for UTIs
      using a focused educational program. The increased scores on the internal MHLC
      Scale suggest that individuals in the treatment group felt that they had more
      control over their health behavior after receiving a UTI educational
      intervention.

PMID- 15156938
TI  - Effects of exogenous testosterone on testicular function during the chronic phase
      of spinal cord injury: dose effects on spermatogenesis and Sertoli cell and sperm
      function.
AB  - INTRODUCTION: Exogenous testosterone has been shown to attenuate spinal cord
      injury (SCI)-related regression of spermatogenesis in the rat. The current
      experiment investigated the effects of exogenous testosterone in testicular and
      sperm functions in the rat during the chronic phase of SCI. METHODS: Chronic SCI
      rats were given subcutaneous implants of testosterone-filled silastic capsules
      (TC). Northern blot cDNA hybridization was used to measure testicular levels of
      Sertoli cell- and germ cell-specific transcripts. Western blot and
      immunohistochemistry were used to determine protein level and cellular
      localization, respectively, of cyclic adenosine monophosphate-responsive element
      modulator (CREM) in the testes. Flow cytometry was used to determine sperm
      viability and mitochondrial potential. RESULTS: Spontaneous restoration of
      spermatogenesis occurred in 7 of the 8 untreated SCI rats. Although exogenous
      testosterone restored complete spermatogenesis in all SCI rats, regressed
      seminiferous epithelium remained in 30% to 70% of tubular cross sections in these
      rats. These effects were associated with altered responses of germ cell-specific
      mRNA transcripts to exogenous testosterone, and abnormal cellular distribution of
      CREM. Sperm of untreated SCI rats exhibited lowered motility, viability, and
      mitochondrial potential. Implantation of 10 cm of TC worsened sperm motility in
      sham control and SCI rats, but restored sperm viability and mitochondrial
      potential in SCI rats. CONCLUSION: Administration of exogenous testosterone to
      SCI rats during the chronic phase of injury failed to facilitate spermatogenic
      restoration over that achieved in untreated SCI rats. Abnormalities in
      postmeiotic spermatogenic differentiation could contribute to these effects, and
      perhaps the production of sperm with abnormal morphology and/or functions during
      the chronic phase of SCI.

PMID- 15156939
TI  - Internal consistency and responsiveness of the Skin Management Needs Assessment
      Checklist post-spinal cord injury.
AB  - OBJECTIVE: To evaluate the internal consistency and sensitivity to change of the
      Skin Management needs assessment checklist (SMnac), a measure specifically
      developed for the spinal cord injury (SCI) population to assess skin management
      ability and equip individuals with the skills they need to prevent pressure ulcer
      development. STUDY DESIGN: Consecutive series, psychometric evaluation study.
      SETTING: Spinal Cord Injuries Rehabilitation Unit, United Kingdom. PARTICIPANTS:
      317 participants with traumatic or nontraumatic SCI. MEASURE: This study used the
      SMnac, which assesses the ability to perform skin checking, pressure relief, and
      the prevention of skin insults based on the individual's perception of his or her
      ability to independently undertake skin management activities. RESULTS:
      Assessment of internal consistency produced a Cronbach's alpha for this scale of
      0.85. A paired-samples t test was used to evaluate the SMnac's sensitivity to
      change. There was a significant difference between the first and second SMnac
      scores (t = - 24.38, df = 186, P < 0.001). CONCLUSION: The SMnac has high
      internal consistency and sensitivity to change. The SMnac provides constructive
      assessment of skin management, specifying problems for individuals with SCI,
      standardizing the critical inputs required to meet rehabilitation targets, and
      measuring the effects of those inputs and their relationship to other mediating
      variables and expected outcome.

PMID- 15156940
TI  - Worsening myelopathy masked by peripheral nerve disorders.
AB  - BACKGROUND/OBJECTIVE: Peripheral nerve disorders--whether due to peripheral nerve
      entrapment or to polyneuropathy--can alter the signs of myelopathy, masking both
      the sensory loss and distal hyperreflexia. Diagnosis of worsening myelopathy may
      be missed when there is a coexisting peripheral nerve disorder. METHODS: This
      study is a case description and analysis of 3 consecutive cases identified over 2
      years. RESULTS: Three cases were identified in which the diagnosis of worsening
      myelopathy was missed and treatment was delayed because neurologic decline was
      attributed to a coexisting peripheral nerve disorder. This report describes 2
      cases of posttraumatic syringomyelia masked by superimposed peripheral nerve
      entrapments and 1 case of cervical myelopathy due to cervical spinal stenosis
      from ossification of the posterior longitudinal ligament masked by diabetic
      polyneuropathy. CONCLUSION: It is important to continually question whether the
      working diagnosis of peripheral nerve disorder explains the clinical findings,
      given neurologic decline; or whether a superimposed worsening myelopathy may
      coexist. Early diagnosis of worsening myelopathy is important, because prompt
      treatment of syringomyelia and myelopathy due to cervical spinal stenosis may
      yield better outcomes. Early diagnosis is aided by (a) considering alternative
      and multiple diagnoses, (b) assessing spinothalamic as well as posterior column
      sensation and assessing these sensory modalities for proximal as well as distal
      limbs, (c) assessing tendon hyperreflexia of proximal as well as distal limb
      muscles, and (d) utilizing electrodiagnostic tests that can identify myelopathy.

PMID- 15156941
TI  - Metabolic and cardiac responses to robotic-assisted locomotion in motor-complete
      tetraplegia: a case report.
AB  - BACKGROUND/OBJECTIVE: To examine acute metabolic responses to treadmill
      locomotion in a participant with motor-complete tetraplegia. METHODS: The
      participant--a woman with a chronic ASIA B C3-C4 spinal cord injury--walked on a
      treadmill with 40% body weight support (BWS) and robotic assistance. Oxygen
      consumption (VO2), minute ventilation (VE), and heart rate (HR) were measured
      during seated resting, supported standing, and 40 minutes of walking with
      stepping assistance from a Lokomat-driven gait orthosis. RESULTS: A resting VO2
      equal to 50 milliliters per minute was predictably low, and did not change after
      the participant assumed an upright posture. Both VO2 and VE increased immediately
      upon onset of locomotion, suggesting a neurogenic rather than a humoral
      regulatory response to movement. VO2 averaged 2.4 metabolic units (METS) during
      locomotion at an average expenditure of 2.98 kilocalories per minute. HR was
      unaltered by standing, but during locomotion averaged 1 7 beats higher than
      during resting. Increases in VE but not VO2 upon standing, and decreases in VO2
      but not VE immediately after walking, rule out changes in VE alone as the source
      for increased VO2 during walking. CONCLUSION: The data collected on this single
      participant show that treadmill locomotion with BWS and robotic assistance
      elicits a metabolic response to treadmill gaiting characterized by increased VO2,
      VE, HR, and caloric expenditure.

PMID- 15156942
TI  - The Southeastern Surgical Congress: past, present, and future.

PMID- 15156943
TI  - A Hamblin Letton Lecture. The continuing need to attract surgery students to
      surgical specialty careers: a step forward but at what expense?

PMID- 15156944
TI  - Rapamycin inhibits release of tumor necrosis factor-alpha from human vascular
      smooth muscle cells.
AB  - Neointimal proliferation with plaque formation is the principal cause of coronary
      artery disease. In the neointima, inflammatory cytokines like tumor necrosis
      factor-alpha (TNF-alpha) are expressed by vascular smooth muscle cells (VSMCs).
      These cytokines stimulate proliferation and migration of VSMCs, events that are
      crucial to neointima formation. Stents, liberating rapamycin, have been shown to
      reduce neointima formation in human coronary arteries. The purpose of this study
      was to determine if rapamycin could inhibit the production of TNF-alpha by VSMCs.
      With institutional review board approval, VSMCs were cultured from saphenous vein
      segments obtained from five patients. Cells were identified as VSMC by
      immunostaining for smooth muscle alpha-actin. Cells were exposed to bacterial
      lipopolysaccharide (LPS), LPS plus rapamycin, or LPS plus isoproterenol for 24
      hours. Cells with no treatment served as controls. The culture medium was then
      removed and analyzed for TNF-alpha. Additionally, the effect of treatment on
      viability was determined by assay of mitochondrial activity. TNF-alpha released
      into the culture medium is expressed as pg TNF-alpha/mg cell protein. Statistical
      analysis was by ANOVA. In control cells, TNF-alpha was undetectable in the
      culture medium. The addition of LPS (10 microg/mL) increased TNF-alpha release to
      4312 +/- 705 pg/mg at 24 hours. The addition of 1 ng/mL rapamycin with LPS
      reduced TNF-alpha production 50 per cent (P < 0.01 vs LPS alone). A similar
      reduction of TNF-alpha release was seen with 1 microM isoproterenol. LPS,
      rapamycin, or isoproterenol did not affect cell viability. These data show that
      rapamycin effectively inhibits the release of TNF-alpha from VSMCs stimulated
      with inflammatory mediators like LPS. Rapamycin is as effective as agents that
      raise intracellular cyclic AMP (e.g., isoproterenol). Therefore, a potential
      mechanism for the effectiveness of rapamycin-releasing stents is reduction of
      inflammatory cytokine expression by VSMCs.

PMID- 15156945
TI  - Congenital diaphragmatic hernia repair on extracorporeal life support: a decade
      of lessons learned.
AB  - Congenital diaphragmatic hernia (CDH) is a vexing anomaly that manifests with
      variable pulmonary compromise in neonates. More than one-third of neonates with
      CDH require extracorporeal membrane oxygenation (ECMO) for refractory pulmonary
      hypertension (PHN). To assess the outcome of neonates having CDH repair on ECMO,
      we reviewed our experience for babies treated between 1992 and 2003. Of 97
      neonates with CDH, 40 required ECMO, and 30 were repaired on bypass. Eighteen
      were supported by veno-venous bypass (VV) and 12 by veno-arterial bypass (VA).
      While on ECMO, transfusion requirements increased twofold postoperatively (15 to
      33 cc x kg(-1) day(-1), P = 0.03) and then significantly decreased after
      decannulation (1.5 cc x kg(-1) x day(-1), P < 0.01). Non-intracranial hemorrhage
      occurred in 7 (23%) infants and intracranial hemorrhage in 3 (10%). Twelve (40%)
      infants died; one (3%) on ECMO secondary to refractory PHN. The mean length of
      stay for the 18 (60%) survivors was 48 days. Comparisons between survivors and
      nonsurvivors showed a significantly increased mortality for infants placed on VA
      bypass (P < 0.01). However, no other variable was predictive of survival. We
      conclude that CDH repair on ECMO is technically feasible, shows similar survival
      to the Extracorporeal Life Support Organization (ELSO) registry, and is
      associated with few bleeding complications.

PMID- 15156946
TI  - Repair of giant abdominal hernias: does the type of prosthesis matter?
AB  - Closure of the abdominal wall after trauma or major surgery may be difficult due
      to visceral edema or fascial weakness; thus, the risk of developing a ventral
      hernia (VH) is high. Commonly, these hernias are repaired using a prosthetic
      mesh. Complications following mesh repair can develop. We hypothesize that the
      type of prosthetic material affects outcome. This is a retrospective chart review
      of patients admitted from 1996 to 2002 undergoing VH (> or = 20 x 10 cm) repair
      with prosthetic mesh. Data collected included age, sex, and race. Patients were
      stratified by prosthetic material as follows: Gore-Tex (GR), Marlex + Gore-Tex
      (MG), Marlex (MR), and Marlex + Vicryl (MV). For the purpose of clinical
      analysis, the groups were collapsed into subgroups: Gore-Tex exposure (GT) or non
      Gore-Tex exposure (NG). Outcome measures were hernia recurrence (HR), wound
      infection (WI), and fistula formation (FF). Statistical analysis utilized chi2
      test and Fisher's exact test. There were 55 VH repairs in 37 patients. The mean
      age was 43.9 (+/- 16.3), males out-numbered females 22 (59.5%) to 15 (40.5%). The
      majority of the patients were Caucasian (29; 78.4%). There were 30 trauma
      patients (81.1%), and 7 general surgery patients (18.9%). The HR for the study (n
      = 55) was 20 (36.4%), the WI was 17 (30.9%), and the FF was 3 (5.5%). GR group
      (6; 66.7%) had a significant higher wound IF rate than MR group (8; 26.7%) (Chi P
      = 0.02, Fisher P = 0.047). All other group comparisons (HR, WI, and FF) were N.S.
      The Gore-Tex versus non-Gore-Tex subgroup comparison results were as follows: GT
      (n = 18) had a WI 8 (44.4%), HR 6 (33.3%), and FF 0 (0%). NG (n = 37) had a WI 9
      (24.3%), HR 14 (37.8%), and a FF 3 (8.1%). There was a trend toward a higher
      wound infection in the GT versus NG, but it did not reach statistical
      significance. We conclude that 1) the wound infection rate was higher in the Gore
      Tex versus the Marlex group (Chi P = 0.02, Fisher P = 0.047). Wound infection in
      the presence of Gore-Tex usually mandates the removal of the mesh resulting in a
      hernia recurrence. 2) There was a trend toward a higher wound infection in the GT
      (44.4%) versus NG (24.3%), but it did not reach statistical significance.

PMID- 15156947
TI  - Sentinel lymph node mapping and biopsy for ductal carcinoma in situ and other
      controversial indications.
AB  - This review discusses the currently available literature regarding three
      controversial indications for sentinel node mapping for breast cancer patients.
      For women with ductal carcinoma in situ (DCIS), the use of sentinel lymph node
      mapping (SLNM) should be limited to women having a mastectomy. For patients with
      multifocal breast carcinoma, SLNM is accurate when a retroareolar injection
      technique is employed in the procedure. When treatment plans for node-negative
      patients call for neoadjuvant chemotherapy, accurate sentinel node mapping can be
      performed prior to the administration of chemotherapy. The resolution of these
      and other controversies should result in the expansion of the number of patients
      evaluated with SLNM in the future.

PMID- 15156948
TI  - Technical advances in sentinel lymph node biopsy for breast cancer.
AB  - Technical advances in the past several years have simplified and improved
      sentinel lymph node (SLN) biopsy for breast cancer. The use of alternative
      injection sites (skin or subareolar) yields high SLN identification rates and may
      shorten the learning curve associated with standard peri-tumoral injection. The
      dual-agent (radiocolloid plus blue dye) technique is now recommended to decrease
      false-negative rates, especially when surgeons are just learning how to perform
      SLN biopsy. Methylene blue may be an acceptable substitute for isosulfan blue dye
      and is associated with fewer hypersensitivity reactions. Hand-held gamma probes
      are now smaller and more maneuverable, with better shielding for directional
      detection of gamma rays. Routine preoperative lymphoscintigraphy can be avoided,
      thus facilitating operating room scheduling. Surgeons can use minimally invasive
      techniques to identify and remove internal mammary SLNs.

PMID- 15156949
TI  - The use of frozen section and immunohistochemistry for sentinel lymph node biopsy
      in breast cancer.
AB  - Intraoperative pathologic evaluation of the sentinel lymph node (SLN) may guide
      immediate (synchronous) completion axillary lymph node dissection (ALND) for up
      to two-thirds of patients with nodal disease for breast cancer. The false
      negative rates average one-third of cases, and one must be aware of false
      positive results as this would result in unnecessary and morbid completion ALND.
      Currently, the use of immunohistochemistry (IHC) is controversial. There is no
      question that cytokeratin staining improves the sensitivity; however, there is no
      evidence that any of these "positive" cells are clinically significant and
      warrant therapy. Prospective randomized trials will be necessary to confirm or
      debunk the hypothesis that "sub-micrometastatic" disease has clinical
      significance.

PMID- 15156950
TI  - Update on the NSABP and ACOSOG breast cancer sentinel node trials.
AB  - Sentinel lymph node biopsy in women with breast cancer has become routine in many
      surgical practices; yet basic questions regarding the procedure remain
      unanswered. The National Surgical Adjuvant Bowel and Breast Project (NSABP) and
      the American College of Surgeons Oncology Group (ACOSOG) trials address the
      issues of morbidity, efficacy, safety, and the significance of low-volume
      disease. NSABP B-32 randomizes women to sentinel lymph node biopsy followed by a
      standard level I and II axillary dissection or sentinel lymph node biopsy without
      dissection unless metastatic disease is noted by H&E examination. Overall
      survival, disease-free survival, and morbidity serve as end points. Further
      pathologic evaluation of the lymph nodes with immunohistochemistry will be
      performed by the study center. This study is nearing its anticipated accrual
      goal. Patients enrolled in the now-closed ACOSOG Z0010 trial underwent bone
      marrow aspiration just prior to sentinel node biopsy. Immunocytochemical analysis
      of the marrow will be compared to sentinel lymph node (SLN) biopsy to determine
      prognostic accuracy. ACOSOG Z0011 randomizes women undergoing breast-conserving
      therapy with low-volume axillary disease to completion axillary dissection or
      observation. Overall survival, disease-free survival, local regional control, and
      morbidity serve as end points. This trial is currently enrolling patients.

PMID- 15156951
TI  - Skin-sparing and nipple-sparing mastectomy: preoperative, intraoperative, and
      postoperative considerations.
AB  - The last several decades have witnessed significant advances in the surgical
      management of breast cancer. Although many have embraced breast conservation as
      the procedure of choice, some patients will still opt for mastectomy for a
      variety of reasons. Recently, the concept of skin sparing mastectomy and
      immediate breast reconstruction has emerged as an option that provides excellent
      cosmetic results while being oncologically safe. However, this surgical approach
      must be considered within a multidisciplinary context, and there are a number of
      perioperative issues that need to be considered. In addition, newer techniques,
      which spare the nipple and/or areola, warrant further examination.

PMID- 15156953
TI  - Augmentation of ischemia/reperfusion injury to endothelial cells by cyclosporin
      A.
AB  - Ischemia/reperfusion (I/R) carries significant injury to endothelial cells in
      transplanted organs and is an important factor in chronic rejection.
      Immunosuppressive drugs, notably cyclosporin A (CyA) and FK506, can potentially
      augment this injury. Here, our goal was to determine the combined effects of I/R
      and CyA or FK506 on endothelial cells. Transformed mouse endothelial cells (SVEC
      4-10) were subjected to ischemia or I/R for 2-24 hours by incubating cells in 100
      per cent N2 (ischemia) followed by 5 per cent CO2 and 95 per cent O2
      (reperfusion) for 24 hours. In separate experiments, CyA or FK506 was added to
      cells subjected to ischemia or I/R. Nonviable cells were determined by Trypan
      blue exclusion assay. All experiments (done in triplicate) were analyzed by
      Student's t test. Increasing ischemia times resulted in a greater number of
      nonviable cells (2% nonviable cells at 0 hours and 57% at 24 hours of I/R).
      Addition of CyA significantly increased the number of nonviable cells when
      compared with the control (I/R only) group (P = 0.014). Interestingly, FK506 did
      not increase the percentage of nonviable cells compared with the control group (P
      = 0.2). Unlike FK506, CyA augments I/R injury to endothelial cells in vitro.
      These findings could be relevant in chronic rejection and transplantation.

PMID- 15156952
TI  - Incurable colorectal carcinoma: the role of surgical palliation.
AB  - About 20 per cent of patients with carcinoma of the colon or rectum present with
      metastatic disease. Surgeons are frequently asked to consider resection or other
      operative procedures in these patients for palliation. We performed this review
      to determine whether patients presenting with known metastatic colorectal cancer
      derive benefit from surgical intervention. We performed a retrospective review of
      all patients with M1 carcinoma of the colon or rectum who were identified from
      the University of Mississippi Medical Center Cancer Registry from April 1985
      through February 2003. Patients who underwent hepatic and/or pulmonary resection
      with curative intent were excluded from analysis, as were patients with
      metachronous metastases. Eighty patients with M1 colorectal cancer who did not
      undergo surgery with curative intent were identified, and in 74 of these,
      complete medical records and follow-up were available. Forty-nine of the 74
      patients (66%) underwent an operation, and 25 were managed nonoperatively.
      Indications for surgery included bowel obstruction, active hemorrhage, severe
      anemia from gastrointestinal bleeding with requirement for blood transfusions,
      intractable pain, and perforation of the colon. Average survival was 11.2 months
      for operative patients versus 6.5 months for nonoperative patients (P < 0.05).
      Thirty-six patients who underwent resectional procedures had a postoperative
      hospitalization of 7.5 days and a median survival of 11.5 months. Thirteen
      patients who had a nonresectional procedure had an average postoperative stay of
      9 days and a median survival of 4 months. Median survival in those who did not
      undergo an operation was 4.8 months. Although metastatic colorectal carcinoma
      cannot usually be cured by surgical intervention, many patients who present with
      metastatic disease will benefit from palliative operations with relatively short
      hospitalizations and reasonable survival. Those who are not candidates for
      resection of the primary tumor have shorter survival times. Surgery can alleviate
      many of the distressing symptoms in patients with metastatic colorectal
      carcinoma.

PMID- 15156954
TI  - Pediatric blunt trauma resulting in major arterial injuries.
AB  - Ten children, aged 4 to 14 years, sustaining blunt arterial trauma from motor
      vehicle collisions (6), bicycle accidents (2), and falls (2) were identified over
      a 10-year period. The arteries injured included the common iliac (3), abdominal
      aorta (2), carotid (2), brachial (2), and the subclavian, renal, and femoral
      artery (1 each). One patient had three arterial injuries. Six patients had
      associated injuries including a pelvic and lumbar spine fracture, Horner's
      syndrome, liver laceration, skull fracture, open humerus fracture, small bowel
      serosal tear, and a brachial plexus injury. Definitive diagnosis was made using
      arteriography (6), computed tomography (CT) scan (2), and physical examination
      (2). The types of arterial injuries found included incomplete transection,
      complete transection with pseudo-aneurysm formation, traumatic arteriovenous (AV)
      fistulas, complete occlusion, and dissection. Repair was accomplished by
      hypogastric artery interposition or bypass grafting, synthetic grafting with
      polytetrafluoroethylene (PTFE), reverse saphenous vein grafting, or primary
      repair, depending on the circumstances. An AV fistula between the carotid artery
      and cavernous sinus was embolized. All grafts remained patent with exception of
      the aorto-renal bypass graft at follow-up ranging from 1 month to 3 years. The
      principles for repairing vascular injuries in children are slightly different
      than those in adults. Every effort should be made to use autogenous tissue such
      as the hypogastric artery or saphenous vein for repair if possible. If not, PTFE
      grafts can be used, although the long-term patency of these grafts in growing
      children is not known.

PMID- 15156955
TI  - Common bile duct papillary adenoma causing obstructive jaundice: case report and
      review of the literature.
AB  - Common bile duct (CBD) adenomas are rare tumors that often present in a fashion
      similar to their malignant counterparts. We report a case of a papillary CBD
      adenoma causing obstructive jaundice. We also present a review of the CBD
      adenomas found in the English literature through a Medline search (1970-2003). A
      74-year-old female presented with a 10-day history of pruritus, progressive
      painless jaundice, acholic stools, bilirubinuria, and 10-lb weight loss.
      Abdominal exam showed no masses. Abdominal ultrasound (U/S) showed cholelithiasis
      without choledocholithiasis. Endoscopic retrograde cholangiopancreatography
      (ERCP) and endoscopic U/S revealed a shelf-like stricture, 1.5 cm long and 0.9 cm
      in diameter, located in the distal CBD. At the time of biliary stent placement,
      fine-needle aspiration showed benign ductal epithelial cells in sheets and
      clusters. Abdominal CT scan showed a low attenuation 15 x 17 mm lesion in the
      head of the pancreas that abutted the superior mesenteric vein (SMV) but no
      metastatic lesions. We performed a standard pancreaticoduodenectomy (Whipple
      procedure). Final pathology showed a papillary adenoma without evidence of
      dysplasia in the distal common bile duct proximal to the ampulla of Vater. The
      incidence of these tumors and their potential for malignant degeneration is
      unknown. Pancreaticoduodenectomy is an effective means of treatment and cure for
      CBD adenoma.

PMID- 15156956
TI  - Impact of age on the outcome of liver resections.
AB  - The purpose of this study was to evaluate the influence of age on the outcome of
      liver resections. One hundred five consecutive hepatic resections were divided
      into two groups: > or = 65 years old [old group (O-group)] and < 65 years old
      [young group (Y-group)]. The two groups were first compared to evaluate the
      distribution of the variables potentially affecting the postoperative course,
      including primary diagnosis, concomitant diseases, previous upper abdominal
      surgery, type of operation (major or minor resection), associated procedures,
      presence and length of portal clamping, intraoperative blood losses and
      transfusions, and length of operation. The outcome of hepatic resections in the
      two groups was comparatively evaluated in terms of postoperative mortality,
      morbidity, transfusions, and length of postoperative hospitalization. The Y-group
      included 61 resections in 60 patients, mean age 52 +/- 10 years (mean +/- SD),
      range 23-64 years, whereas the O-group included 44 resections in 43 patients,
      mean age 71 +/- 4 years (mean +/- SD ), range 65-82 years. The O-group included
      more hepatocellular carcinomas (45.4% vs 18.0%, P = 0.002) and chronic liver
      diseases (40.9% vs 18.7%, P = 0.017); the median length of operation was slightly
      higher in the Y-group (300 minutes vs 270 minutes, P = 0.003). Both O-group and Y
      group were comparable (P = n.s.) when evaluated for all other listed variables.
      As far as concerns the outcome of hepatic resections in the two groups, the
      length of postoperative hospitalization was identical (median 9 days, 5-60 days),
      whereas transfusions of packed red cells (O-group vs Y-group: 25.0% vs 16.3%, P =
      0.30) or fresh frozen plasma (O-group vs Y-group: 13.6% vs 6.5%, P = 0.053) were
      not statistically different. Postoperative mortality included one case among
      young patients whereas no deaths were recorded among elderly patients.
      Postoperative morbidity was higher in Y-group than in O-group (31.5% vs 20.5%, P
      = 0.59). The age factor does not negatively affect the outcome of liver
      resections.

PMID- 15156957
TI  - Prognostic factors of insular versus papillary/follicular thyroid carcinoma.
AB  - The study aims were to characterize patients with insular thyroid cancer and to
      provide data on patient outcome after surgical therapy. We compared nine patients
      with insular thyroid cancer at the Department of Surgical Science of "La
      Sapienza" University of Rome with 27 patients of similar age and tumor size who
      had follicular and papillary cancer, for a minimum follow-up period of 24 months
      (range, 24-72 months). All of the patients examined underwent total
      thyroidectomy. Vascular invasion was observed in 44.4 per cent of insular
      carcinomas (P < 0.05 vs papillary carcinomas). No significant differences were
      observed regarding diagnostic method, multifocality, tumor nodes metastases
      (TNM), or stage. The death rate of patients with insular carcinoma (33.3%) was
      found to be higher than that of patients with follicular carcinoma (P < 0.05) and
      papillary carcinoma (P < 0.01). Relapsing lymph-node pathologies were observed in
      4 patients (44.4%) with insular carcinoma (P < 0.05 vs those with follicular and
      papillary carcinomas). Distant metastases were observed in 66.6 per cent of
      insular carcinomas (P < 0.005 vs follicular carcinoma and P < 0.001 vs papillary
      carcinoma). At the end of follow-up, 2 patients (22.2%) with insular carcinoma
      were disease-free (P < 0.001 vs those with follicular and papillary carcinomas).
      Our study demonstrates an unfavorable prognostic role of the insular phenotype of
      thyroid cancer, such that this tumor can be classified as an autonomous clinical
      and pathological entity.

PMID- 15156959
TI  - Budget-busting drug gets institutional oversight.

PMID- 15156958
TI  - Reducing medication errors in a surgical residency training program.
AB  - Medication errors contribute to in-hospital morbidity and mortality. Teaching
      hospitals and the surgical residency training programs they support should take
      proactive steps to reduce error frequency. In order to accomplish meaningful
      error reduction, we must first define the scope and nature of the problem.
      Pharmacists at the Monmouth Medical Center prospectively recorded medication
      prescribing errors made by surgical residents during 2 years. These data were
      reviewed to determine the types of medication errors made most frequently by
      surgical house officers. Seventy-five medication-prescribing errors were made by
      surgical house staff in the years 2001 and 2002. Thirty-three of these errors
      involved orders for antibiotic therapy. Errors that could not be directly
      attributed to knowledge deficits were responsible for 36 of the 75 errors (48%),
      whereas specific knowledge deficits were responsible for 39 of the 75 errors
      (52%). Twentyeight of the 36 errors not directly attributable to knowledge
      deficits (78%) were made at the postgraduate year one level, whereas only 15 of
      the 39 knowledge deficit errors (38%) were made at the postgraduate year one
      level. Though targeted education to address specific knowledge deficits may
      substantially reduce the occurrence of "knowledge deficit" medication errors
      within surgical residency training programs, more costly measures such as the
      implementation of physician computerized order entry will likely be needed to
      reduce maximally the frequency of medication ordering errors. Many prescribing
      errors cannot be attributed to specific knowledge deficits.

PMID- 15156960
TI  - HHS task force hears concerns about importation, drug prices.

PMID- 15156961
TI  - Experts debate drug importation.

PMID- 15156962
TI  - Pharmacists should heed antikickback law, experts advise.

PMID- 15156963
TI  - FDA improves communication about drug shortages.

PMID- 15156964
TI  - FDA approves generic OxyContin.

PMID- 15156965
TI  - Gefitinib: a new antineoplastic for advanced non-small-cell lung cancer.
AB  - PURPOSE: The pharmacology, pharmacokinetics, and safety of gefitinib and its role
      in the management of non-small-cell lung cancer are reviewed. SUMMARY: Gefitinib
      is indicated for patients with locally advanced or metastatic non-small-cell lung
      cancer who have not responded to chemotherapy with platinum-based regimens or
      docetaxel. Gefitinib is administered orally at a dosage of 250 mg/day. Peak
      plasma levels are attained within 3-7 hours and steady-state levels are achieved
      in 7-8 days. Food does not affect the drug's absorption. Gefitinib is metabolized
      by the cytochrome P-450 isoenzyme system and may be affected by other drugs that
      influence this enzyme activity. Its elimination half-life is 14-48 hours.
      Clinical trials have shown an average response rate of 93% when gefitinib is used
      as a second- or third-line agent. Median survival with gefitinib therapy is 3-6.6
      months. There was no response or survival benefit with the addition of gefitinib
      to standard two-drug combination chemotherapy regimens in two large, randomized,
      placebo-controlled trials. However, there is some evidence that the combination
      of gefitinib and docetaxel may be more active than docetaxel alone. Gefitinib has
      been shown to improve pulmonary symptoms and quality of life in patients who did
      not have an objective response to treatment. The most common adverse effects are
      diarrhea and skin rash. Severe interstitial lung disease, which may be fatal,
      occurs at a rate of approximately 1%. CONCLUSION: Gefitinib is active as a second
      or third-line agent in patients who have few therapeutic options available after
      initial and first-line salvage chemotherapy have failed.

PMID- 15156966
TI  - Discontinuation and reinstitution of medications during the perioperative period.
AB  - PURPOSE: The issues regarding the discontinuation and reinstitution of long-term
      therapies, including cardiovascular agents, anticoagulants and antiplatelet
      agents, central nervous system agents, and herbal medicines, in the perioperative
      period are discussed. SUMMARY: It is estimated that one fourth of all patients
      undergoing a surgical procedure are taking long-term medications. The issues
      surrounding the decision to discontinue such medications before surgery and when
      to reinstitute them are complex. In the preoperative period, it is important to
      avoid the use of medications that may negatively interact with anesthetic agents.
      Postoperatively, the concern shifts toward avoiding withdrawal symptoms that may
      develop and possible progression of the underlying disease if the medications are
      not restarted in a timely fashion. The potential for decreased gastrointestinal
      motility in the postoperative patient, which may reduce the efficacy of oral
      medications, must also be considered. Antihypertensive medications may cause
      cardiovascular complications, such as hypotension or myocardial ischemia.
      Psychoactive medications may cause prolonged sedation and withdrawal symptoms may
      develop. Antithrombotic agents may increase the risks of bleeding during surgery.
      Several herbal medicines may cause a combination of these effects. CONCLUSION:
      The decision to withhold and restart medications should be based on available
      clinical data and expert opinion. Health care professionals should exercise
      diligence in obtaining an accurate medication history on all preoperative
      patients and in reviewing the medications in the postoperative orders.

PMID- 15156968
TI  - Substance use by pharmacy and nursing practitioners and students in a
      northeastern state.
AB  - PURPOSE: The prevalence and predictors of substance use among pharmacists and
      nurses and pharmacy and nursing students were studied. METHODS: During summer
      2002, pharmacists and nurses in a northeastern state were mailed an anonymous
      survey to determine their use of alcohol, tobacco, and commonly abused drugs; to
      determine their ease of access to controlled substances; and to measure their
      family history of alcohol and drug problems. A similar but not identical survey
      was distributed to pharmacy and nursing students during spring 2000. RESULTS: A
      total of 262 usable questionnaires were received from pharmacists and nurses
      (response rate, 72.8%), and 138 usable questionnaires were received from students
      (35.3%). Large majorities of nursing students, pharmacy students, and nurses were
      women. A higher percentage of pharmacists reported having used an opioid or an
      anxiolytic at least once in their lives (24.8% and 14.3%, respectively) than
      nurses (14.5% and 7.8%). Higher percentages of nursing students and nurses
      reported having ever used an unprescribed drug (74.5% of nursing students and
      63.6% of nurses). CONCLUSION: A survey of pharmacy and nursing practitioners and
      students in a northeastern state provided important information on alcohol,
      tobacco, and illicit drug use among these groups and highlighted the need for
      prevention and intervention.

PMID- 15156967
TI  - Compliance in two medical centers with criteria for use of caspofungin and lipid
      based amphotericin B.
AB  - PURPOSE: Patterns of use and compliance with guidelines for use of lipid-based
      amphotericin B (LBA) and caspofungin at two medical institutions were studied.
      METHODS: Charts of all adult patients receiving LBA or caspofungin or both in
      combination at the University of California at San Francisco Medical Center
      (UCSF) and the University of California at San Diego Medical Center (UCSD)
      between January 1 and October 22, 2001, were reviewed. RESULTS: A total of 140
      episodes of use of LBA, caspofungin, or the combination were identified at the
      two institutions. The primary indication for therapy with LBA was candidiasis
      (34% of episodes), whereas caspofungin and the drug combination were most
      commonly used for aspergillosis (43% and 71% of episodes, respectively). UCSF
      used the antifungal agents in accordance with its guidelines in 25% of the
      episodes of use and UCSD in 56%. Despite a higher qualifying serum creatinine
      (SCr) concentration for use of LBA at UCSF than at UCSD, the mean SCr
      concentration upon use was lower at UCSF. Among UCSF patients who did not meet
      the strict SCr criteria for use of either agent, most had concomitant renal
      failure as defined by a creatinine clearance of <25 mL/min, known risk factors
      for amphotericin B-associated nephrotoxicity, or breakthrough fungal infections
      while receiving alternative antifungal therapy. The UCSF pharmacy and
      therapeutics committee recommended that these factors be included in the
      indications for use of these agents. CONCLUSION: Compliance with criteria for use
      of LBA and caspofungin at two medical centers was inconsistent, probably because
      the initial criteria were insufficient in defining the conditions that justified
      the drugs' use.

PMID- 15156969
TI  - Using a personal digital assistant to document pharmacotherapeutic interventions.

PMID- 15156970
TI  - Clinical pharmacy services in an emergency department.

PMID- 15156971
TI  - ASHP Guidelines on the Pharmacist's Role in the Development, Implementation, and
      Assessment of Critical Pathways.
AB  - Because pharmacotherapy is a central component of many critical pathways,
      pharmacists should take leadership roles in their development, implementation,
      and assessment. Pharmacists can improve the development of critical pathways by
      ensuring the evidence-based selection of medications, establishing measures for
      monitoring patients for drug efficacy and adverse effects, and evaluating the
      proposed critical pathway for patient safety. Pharmacists can improve the
      implementation of critical pathways by documenting processes and outcomes,
      ensuring proper patient selection and medication use, monitoring patients for
      drug efficacy and adverse effects, and providing for continuity of care.
      Pharmacists can improve the assessment of critical pathways by measuring and
      analyzing processes and outcomes, disseminating the results of those analyses,
      and reviewing the critical pathways' pharmacotherapy to keep pace with changes in
      best practices.

PMID- 15156972
TI  - Actions of the ASHP Board of Directors--meeting of January 15-16, 2004.

PMID- 15156973
TI  - Upchurch Lecture--2003.

PMID- 15156974
TI  - Endoscopic-assisted face lift: review of 200 cases.
AB  - The use of endoscopic techniques in facial esthetic surgery has gained increasing
      popularity in the last decade. Endoscopic forehead rejuvenation became a reliable
      technique and an attractive option for both the surgeon and the patient. The use
      of the endoscope in face and neck lift surgery did not gain the same popularity,
      as explained by the relative few indications for this technique. In this study,
      we retrospectively review a series of 200 patients who underwent endoscopic
      assisted face-lifts alone or in combination with other esthetic procedures. We
      divided the patients into 4 groups according to the type of incisions and the
      surgical approach used in each of them. We also reviewed the current status of
      using the endoscope in face and neck lift surgery. The technique described in
      this study uses limited access incisions (limited postauricular, submental, and
      temporal scalp) to reposition the ptotic facial elements, while avoiding the
      preauricular and postauricular scarring when indicated. Under endoscopic
      visualization, the composite face-lift flap elevates the malar fat pad above the
      zygomaticus muscle to the nasolabial fold. The lower-lid orbicularis oculi muscle
      is incorporated and lifted with composite flap through the lower blepharoplasty
      incision. The jowl area is contoured by tangential excision and tightening of the
      lateral platysma. Pretunneling and hydrodissection defines the plane of
      dissection and helps to reduce the bleeding during facial and cervical flap
      elevation. In this study, endoscopic techniques were applicable in selected
      patients undergoing facial rejuvenation with goals of decreased scarring.
      Indications for using the technique include young patients (eg, less than 50
      years) with a relatively small amount of skin excess or older patients with thick
      skin and minimal skin redundancy. The technique is particularly attractive to the
      male patient, by avoiding the preauricular incision and the disruption of the
      beard line. Patients with excess skin underwent the standard cervicofacial
      incision. In this group the endoscope was used as a tool for better magnification
      and illumination.

PMID- 15156975
TI  - Surgical anatomy of the midface as applied to facial rejuvenation.
AB  - Distinct anatomic structures provide attachments and support for the soft tissues
      of the central third of the face. Over time, laxity of these structures and
      descent of the malar fat pad contribute to the characteristic changes seen in the
      aging face. Mobilization of the midface soft tissues to allow reelevation of the
      malar fat pad is an effective method of rejuvenating the midface. A focused
      anatomic dissection of 8 fresh cadaver heads was performed to evaluate 4 soft
      tissue structures that control mobilization of the malar fat pad. Specifically,
      the orbicularis retaining ligaments, the lateral orbital thickening, prezygomatic
      space, and zygomatic cutaneous ligaments were evaluated. The anatomic
      relationship of these structures explains the visible effect of aging in the
      central third of the face. In addition, it correlates with the outcomes of
      surgical rejuvenation as demonstrated in clinical cases. Effective repositioning
      of the malar fat pad was found to be reliably obtained by release of the lateral
      orbital thickening and the orbital retaining ligaments. Suspension of the malar
      soft tissue is in a cephalad direction after release of these structures
      recreates a youthful facial architecture. Motor nerve injury is less likely to
      occur with this technique than with traditional lateral facelift approaches. The
      conclusion reached is that ptosis of the malar fat pad can be corrected safely
      and effectively utilizing either the lower lid blepharoplasty approach or
      temporal prehairline incision. These findings were consistent with clinical data
      from facial rejuvenation procedures.

PMID- 15156976
TI  - Bilateral breast reconstruction with the deep inferior epigastric perforator
      (DIEP) flap: an experience with 280 flaps.
AB  - Bilateral prophylactic mastectomy can reduce the incidence of breast cancer by 87
      to 93% in high-risk individuals and is an appealing option for many patients if
      reconstruction can be provided with acceptable morbidity and outstanding esthetic
      results. Autogenous breast reconstruction techniques have evolved over the last
      20 years to meet this goal. Familiarity with the deep inferior epigastric
      perforator (DIEP) flap led us to carry out simultaneous bilateral breast
      reconstruction with acceptable morbidity and superior esthetic outcome in 3
      patient groups: (1) after bilateral prophylactic mastectomy, (2) after
      therapeutic and contralateral prophylactic mastectomy, and (3) after explantation
      of bilateral implant failures. A retrospective review of our experience with 280
      flaps in 140 patients was performed. Average operating times, including time for
      implant removal or mastectomy and reconstruction, was 7.3 hours. Average
      hospitalization was 3.9 days. Significant perioperative complications occurred in
      9 patients (6.4%); all returned to the operating room. This included 7
      microvascular complications, 1 hematoma, 1 seroma, and 1 DVT. Less significant
      complications were divided into early and late. The early complications included
      1.8% partial flap necrosis, 4.2% abdominal apron necrosis greater than 5 cm2,
      2.9% seromas that required intervention, and 5.7% partial breast flap dehiscence.
      Late complications included 12.5% fat necrosis of any size and 2.1% hernia
      formation. Smoking, obesity, age, history of chest wall radiation, and flap size
      were evaluated as risk factors for increased morbidity.

PMID- 15156977
TI  - The case against medial pectoral releases: a retrospective review of 315 primary
      breast augmentation patients.
AB  - Although medial pectoral releases have been recommended as an important component
      of retropectoral breast augmentation surgery, there has been no study that
      documents the benefit or need for this potentially harmful surgical maneuver. In
      this study, 315 patients were retrospectively reviewed to determine the effect of
      medial pectoral muscle releases on breast implant position, visibility, and
      palpability. Five patients had incomplete data, leaving 310 patients available
      for photographic and clinical analysis at an average of 25.7 weeks
      postoperatively (range 5.61-91.6 weeks). All patients received textured, saline
      filled, round, retropectoral implants. Group I (n = 163) had partial medial
      pectoral releases to the level of the superior aspect of the areola. Group II (n
      = 152) had no releases; however, retropectoral pocket dissection was extended
      medially to the arc of the median raphe, where the tendinous origins of the
      pectoralis major muscle are firmly anchored to the anterior aspect of the
      sternum. To assess implant position, the ratio of the intermammary space to the
      lateral breast protrusion (IMS/LBP) was compared for all patients. There was a
      greater decrease in the average IMS/LBP ratio in group II compared with group I,
      (P = 0.0315). This indicates that subpectoral mobilization to the arc of the
      median raphe afforded a proportionally decreased intermammary space, better
      medial envelope fill, and less lateral implant displacement when compared with
      medial pectoral releases. Five patients (3%, P = 0.014) developed breast implant
      visibility and palpability on the medial aspect of the breast mounds, and 2
      patients (1.2%) developed hematomas in group I. One patient (0.6%) developed
      implant distortion with muscle flexion in group II. To explain these results, 6
      pectoral muscles were dissected in 3 female cadavers. Above the fifth rib and
      below the clavicular head, the secure, tendinous origin of the pectoralis major
      muscle arises from the central anterior aspect of the sternum forming an "arc of
      the median raphe." This anatomic feature allows pectoral muscle mobilization
      medially, negating the need for division. Maintaining the integrity of the
      pectoral muscle affords decreased implant visibility and palpability medially and
      decreased patient morbidity while delivering possibly improved esthetic
      proportions by decreasing the intermammary space.

PMID- 15156978
TI  - Factors that influence the completion of breast reconstruction.
AB  - Post mastectomy breast reconstruction continues to evolve in both timing and
      technique; however, multiple surgical procedures are usually required. The
      purpose of this report was to determine the number of secondary procedures
      required to complete the breast reconstruction and factors that influence this
      process. All patients who underwent breast reconstruction at Emory University
      Hospital between 1975 and 2000 were reviewed. The end point and inclusion
      criterion was completion to nipple reconstruction. Secondary procedures were
      determined per patient for either unilateral or bilateral reconstructions, and
      defined as any surgical manipulation of the reconstructed breast, contralateral
      breast, or donor site. The cohort was stratified by timing and method of
      reconstruction. Additional variables included risk factors, radiation therapy,
      and complications. A total of 888 patients completed the reconstructive process
      (738 unilateral and 150 bilateral). The average number of secondary procedures
      was 3.99 for unilateral, and 5.54 for bilateral. Delayed reconstructions had a
      higher number of secondary procedures in both groups. Transverse rectus abdominus
      musculocutaneous flap reconstruction tended to have more secondary procedures
      than implant or latissimus dorsi with or without implant reconstructions.
      Radiation therapy increased the number of secondary procedures in unilateral (3.9
      versus 4.6, P < 0.001) and in bilateral reconstructions (5.7 versus 6.4, P =
      0.032). The number of secondary procedures also increased exponentially with the
      number of risk factors (0-4), and patients with any complication had a higher
      number of secondary procedures for unilateral (4.5 versus 3.6, P < 0.001) and
      bilateral reconstructions (6.4 versus 4.5, P < 0.001). Secondary breast and donor
      site procedures were used as an outcome measure to formulate comparisons.
      Autologous tissue reconstruction required more secondary procedures, likely in
      part to donor site revisions. Delayed reconstruction, the need for radiation
      therapy, any complication, and more risk factors significantly increased the
      number of secondary procedures required to complete the reconstructive process.

PMID- 15156979
TI  - Use of staged rotation-advancement procedures for the treatment of incomplete
      bilateral clefts of the lip.

PMID- 15156980
TI  - Refinements of free tissue transfer for optimal outcome in lower extremity
      reconstruction.
AB  - Advances in microsurgery have revolutionized the management of severe lower
      extremity soft tissue injuries. However, the final optimal result, such as
      cosmesis, is only of secondary concern as limb salvage is the ultimate goal in
      reconstruction. In a continuous effort to obtain the best possible outcome for
      patients, several refinements of free tissue transfers in lower extremity
      reconstruction have been made. Over the past 2 years, 14 patients (8 males: 6
      females; ages 14 to 65 years) underwent lower extremity reconstructions with free
      muscle flaps (7 gracilis, 3 rectus abdominus, and 4 latissimus dorsi) and split
      thickness skin grafts for various soft tissue defects. All patients have obtained
      excellent cosmetic and reconstructive outcomes with an average of 1-year follow
      up. Based on our results, the following refinements are recommended: (1)
      selection of donor muscle flap appropriate to the size and contour requirements
      of the defect; (2) meticulous flap inset into the defect; and (3) if necessary,
      final flap debulking by tangential excision for optimal contouring.

PMID- 15156981
TI  - Quantifying bacterial bioburden during negative pressure wound therapy: does the
      wound VAC enhance bacterial clearance?
AB  - The bacterial colonization of a wound is a recognized detrimental factor in the
      multifactorial process of wound healing. The harmful effects on wound healing are
      recognized to correspond to a level of > 10(5) colonies of bacteria per gram of
      tissue. Negative pressure wound therapy has become an accepted treatment modality
      for acute and chronic wounds with accelerated healing rates observed. It has been
      previously reported that this therapy enhances bacterial clearance, which may
      account for the wound healing effects noted. We retrospectively reviewed 25
      patients' charts undergoing Wound VAC (Vacuum Assisted Closure Device; KCI
      International, San Antonio, TX) therapy with serial quantitative cultures and
      found that there is not a consistent effect of bacterial clearance with the Wound
      VAC. Furthermore, bacterial colonization increased significantly with Wound VAC
      therapy and remained in a range of 10(4)-10(6). Despite this finding, the
      beneficial effects of this treatment modality on wound healing were noted in most
      cases.

PMID- 15156982
TI  - Ex vivo fat graft preservation: effects and implications of cryopreservation.
AB  - There are a variety of recommended methods for harvesting, treating, and
      utilizing autologous fat grafts. Previous work with the MTT assay illustrated
      that various preimplantation handling techniques had minimal effect on the
      viability of fat samples. This assay was used to test the viability of harvested
      fat samples after being stored for up to 8 days in a variety of conditions.
      Surprisingly, freezing the fat before assaying also had no measurable detrimental
      effect, which led us to study this phenomenon in greater detail. The results
      demonstrated that fat stored at subzero temperatures showed remarkable
      maintenance of their mitochondrial metabolic activity as compared with fat stored
      in a 32 degrees C incubator. These data suggest exciting possibilities for
      storage and banking of human adipose tissue, which would reduce patient cost,
      discomfort, and time associated with multiple grafting procedures.

PMID- 15156983
TI  - Breast implants and fibromyalgia: a review of the epidemiologic evidence.
AB  - Although the collective epidemiologic literature does not support an association
      between silicone breast implants and any well-defined or atypical connective
      tissue disease, a recent study raised concern regarding an increased risk for
      fibromyalgia among women with extracapsular ruptured implants. In this review, we
      examine the results of 6 epidemiologic studies which have evaluated the
      occurrence of fibromyalgia among women with breast implants. Two large nationwide
      follow-up studies of women with breast implants in Sweden and Denmark reported
      relative risks for fibromyalgia of 1.0 (95% confidence interval [CI] 0.3 to 3.0)
      and for unspecified rheumatism (including fibromyalgia and myalgia) of 1.2 (95%
      CI 0.9 to 1.5), respectively. Similarly, both a case-control and a cross
      sectional study conducted within rheumatic disease clinics reported no
      association between silicone breast implants and the subsequent development of
      fibromyalgia. The single positive finding, that of a greater than 2-fold excess
      of self-reported fibromyalgia among women with magnetic resonance imaging
      diagnosed extra-capsular ruptures in one study, can be explained by selection
      bias and the use of an inappropriate reference group in the analyses. In the most
      recent study of indefinite connective tissue disease (including fibromyalgia) by
      rupture status, no association was found among unselected Danish women with
      ruptured implants (relative risk 1.0; 95% CI 0.3 to 3.0), and none of the women
      with extracapsular rupture reported fibromyalgia. Thus, the weight of the
      epidemiologic evidence is remarkably consistent and reassuring in failing to
      support an association between breast implants and subsequent fibromyalgia.

PMID- 15156984
TI  - Talc and capsular contracture.
AB  - Capsular contracture, constrictive tightening of scar tissue around implants, was
      historically the primary reason for reoperating breast-implanted women. Yet,
      capsular contracture remains of unknown etiology. Contamination with foreign
      material is one of several suspected causes. Talc, a known fibrogenic agent, was
      recently found in peri-implant scars. A comparison of 192 explanted women was
      designed to investigate the role of talc in the induction of capsular
      contracture. This study included women implanted with silicone gel-filled
      implants for whom tissue samples were available. Patients were evaluated for the
      occurrence of capsular contracture and the presence of intracellular talc
      particles in peri-implant tissues. There was a significant association between
      talc and capsular contracture (odds ratio = 18.0, 95% confidence interval = 5.9
      55, P < 1 x 10(-9)). This study indicates that talc was a major risk factor for
      capsular contracture in women augmented before 1992.

PMID- 15156985
TI  - Subperiosteal midface lifting: a simplified approach.
AB  - A simplified approach to subperiosteal midface lifting with suspension is
      described, which has been performed on 75 patients since 1986. In comparison with
      standard facelifting, this technique results in long-lasting vertical
      resuspension of ptotic midfacial tissues. To date there has been a high rate of
      patient satisfaction with no cases of nerve injury or hematoma. There is a rare
      incidence of minor complications.

PMID- 15156986
TI  - Submuscular augmentation mammaplasty using a perinipple incision.
AB  - The periareolar approach for submuscular augmentation mammaplasty sometimes shows
      a widened or hypertrophic scar and distorts the shape of the areolar-skin
      junction. The authors describe submuscular augmentation mammaplasty using a
      perinipple incision and muscle preservation techniques. The perinipple incision
      can be extended using a backcut within the areola according to the thickness of
      the index finger of the operator. The authors could reach the lateral edge of the
      pectoralis major and lift it while preserving anatomic continuity. The folded,
      smooth saline implant was introduced with a no-touch or minimal-touch technique.
      Implant volumes ranged from 175 to 325 mL. Ten to 25-mL volume was overfilled
      (within the recommended amount), particularly large volume was overfilled in
      patients who had a thin envelope to reduce the palpation of the edge of the
      implant. From August 2000 to December 2002, 306 patients underwent subpectoral
      augmentation mammaplasty via the perinipple approach. Eleven patients complained
      of rippling or a visible fold. There were 7 patients who required a partial
      capsulectomy through the perinipple incision again. The scar was well hidden but
      scar revision was needed in 17 patients as a result of skin slough on the areola
      flap. Of these cases, some were camouflaged using a medical tattooing procedure
      as well. Pain was reduced markedly compared with the axillary approach. In
      conclusion, the perinipple incision has a less visible scar in patients who have
      an ill-demarcated skin-areolar junction and provides a similar operative field
      compared with the periareolar incision. In addition, preservation of the normal
      skin-areola junction is cosmetically successful.

PMID- 15156987
TI  - Reconstruction of post-traumatic frontal-bone depression using hydroxyapatite
      cement.
AB  - The safety and efficacy of hydroxyapatite cement (Bone Source, Howmedica,
      Leibinger, Inc. Dallas, TX) use for the augmentation of post-traumatic frontal
      bone depression was evaluated in a study of 20 consecutive oriental patients
      between June 1998 and July 2000 inclusively. The size of the depressed frontal
      bone ranged from 5 x 5 cm to 8 x 5 cm. The cement was placed in contact with the
      frontal sinus for 12 patients, none of whom revealed a history of paranasal sinus
      mucoperiosteal disease. Follow-up averaged 28 months for all 20 patients.
      Postimplantation evaluations included serial photographs, repeated physical
      examination, and 3-dimensional computed tomography for all patients. The cement
      paste allowed for precise and easy contouring of the bony depression's
      restoration. Meticulous hemostasis is essential to ensure a dry surgical field
      and successful application of the cement. No infection of the surgical site or
      extrusion of the cement was noted for any of our patients, and the contour of the
      reconstructed frontal bone was acceptable esthetically without any secondary
      depression noted during the follow-up period. Three-dimensional computed
      tomographic scans taken 2 years subsequent to implantation revealed good
      preservation of the cement restoration material. Small areas of cement loss due
      to cement absorption into the ambient fluid were noted for 2 patients, but such
      resorption did not appear to esthetically influence the final results. The
      results from this clinical study indicated that hydroxyapatite cement is a
      biocompatible, alloplastic material useful for augmentation of post-traumatic
      frontal-bone depression with stable volume maintenance over time. Judicious use
      of the hydroxyapatite cement offers an alternative to autogenous bone grafts or
      the use of methyl methacrylate for augmentation of the craniofacial skeleton
      among oriental patients.

PMID- 15156989
TI  - Lower limb necrosis after use of the anterolateral thigh free flap: is
      preoperative angiography indicated?
AB  - The large and potentially sensate skin territory, the reliability, and the
      versatility of the anterolateral thigh flap have led to its use for the
      reconstruction of soft-tissue defects of the head and neck region, extremities,
      and trunk. Most authors describe the functional disturbances in the donor site as
      minimal and, to date, no cases of circulatory disturbance of the lower limb as a
      result of anterolateral thigh flap transplantation have been described. The
      authors report a patient with partial necrosis of the foot and calf caused by the
      interruption of the descending branch of the lateral circumflex femoral artery,
      which acted as a critical collateral for the obstructed superficial femoral
      artery. Based on their observations of this patient, the authors recommend
      preoperative angiography of the donor leg in patients in whom palpable popliteal
      pulsations are lacking. Intraoperatively, the chances of postoperative
      circulatory disturbance of the lower leg can be decreased by observation of the
      lower leg circulation after clamping of the flap's pedicle. Immediate arterial
      reconstruction using a venous graft is to be considered in cases in which the
      adequacy of circulation is debatable.

PMID- 15156988
TI  - Primary or delayed closure for the treatment of poststernotomy wound infections?
AB  - OBJECTIVE: The methods of primary versus delayed wound closure for the treatment
      of sternal wound infections after cardiac surgery were retrospectively compared.
      METHODS: From January 2001 to March 2003, 132 patients (median age 66 years, male
      to female ratio 88:44) with sternal wound infection after cardiac surgery were
      treated at our department. After thorough debridement, 35 patients received
      preconditioning of the wound before implementation of definitive therapy; the
      remainder (97 patients) were treated with immediate closure. RESULTS: From the 35
      patients with preconditioning, 19 patients proceeded to delayed primary closure,
      whereas the remaining 14 patients were referred to plastic reconstruction with a
      pectoralis muscle flap. Primary success rate in this group was 100%. In the
      immediate primary closure group, 33 patients experienced 1 or more therapy
      failures, resulting in a recurrence rate of 39%. Fifteen patients received a
      pectoralis muscle flap as definite treatment modality. CONCLUSIONS: Immediate
      primary closure is associated with a high rate of local infection recurrence.
      Surgical debridement and conditioning of the wound until resolution of infections
      with delayed primary closure or plastic reconstruction is suggested as the more
      appropriate treatment modality, with promising results.

PMID- 15156990
TI  - Multifactorial refractory heterotopic ossification.
AB  - Ectopic bone formation or "heterotopic ossification" can follow surgery, trauma,
      or neurologic injury, but the process is usually self-limited, localized to the
      site of injury, and responds to surgical treatment when necessary. Aggressive,
      systemic forms of heterotopic ossification exist that generate lesions that often
      resist surgical treatment and produce a high rate of recurrence. These entities
      typically manifest during infancy as genetic syndromes such as fibrodysplasia
      ossificans progressiva or progressive osseous heteroplasia. The authors describe
      a case of aggressive, systemic heterotopic ossification in an adult that followed
      a motor vehicle accident and multiple surgeries. The patient developed a large
      nonhealing wound around a focus of ectopic bone. Skin grafts failed as a result
      of the recurrence of ectopic bone, and the patient eventually required aggressive
      debridement and delayed rotational flap closure. A brief review of the clinical
      features and surgical treatment of heterotopic ossification is outlined.

PMID- 15156991
TI  - Consequences of radiation accidents.
AB  - Radiation injury attributable to radiotherapy is a topic that has attracted ample
      attention in the literature, especially in a vast number of publications in
      plastic surgery. However, the literature is clearly devoid of compilations
      regarding the effects of ionized radiation accidents. A case of a radiation
      accident is presented. It is nearly impossible to anticipate the extent of
      effects of external irradiation of the skin and subcutaneous tissues. The
      initially healed area should be expected to show late recurrent necrosis.
      Patients exposed to ionized external irradiation are no longer radioactive and
      can be treated as ordinary patients. However, these patients should be followed
      closely for years, keeping in mind the onset of late radiation effects like skin
      necrosis in various parts of the body, skin and other organ cancers, leukemia,
      infertility, hypothyroidism, and cataracts.

PMID- 15156992
TI  - Can academic plastic surgery survive?

PMID- 15156993
TI  - Breast-areola-nipple proportion.

PMID- 15156994
TI  - Ultrasound in the diagnosis and management of fluid collection complications
      following abdominoplasty.

PMID- 15156995
TI  - Canine ecology and socioeconomic factors associated with dogs unvaccinated
      against rabies in a Mexican city across the US-Mexico border.
AB  - A cross-sectional study was conducted to identify ecologic and socioeconomic
      factors associated with dogs unvaccinated against rabies in Mexicali, the capital
      city of Baja California, Mexico (located across the US-Mexico border). A total of
      1100 households were selected by random sampling from a list of all 180,000
      households. A questionnaire was filled in during a personal interview with the
      household head or another adult person to gather information of epidemiological
      interest (such as canine ecology, social and economic factors that might
      influence owners' decision to allow their dog to be vaccinated). There were 910
      dogs identified. The human-to-dog ratio was 4.3:1. The male-to-female dog ratio
      was 1.5:1. Out of 791 dogs > or = 3 months old, 577 (73%) were classified as
      vaccinated against rabies. Most dogs (95%) were not spayed. Neighborhood dogs had
      25 times higher risk of nonvaccination compared to dogs owned by a family. Dogs 3
      11 months old had three times higher risk of nonvaccination compared to dogs > or
      = 1 year old. Dogs that were obtained as a gift, born at home or found had two
      times higher risk of nonvaccination compared to dogs that were reportedly
      purchased. Crossbred dogs had 1.5 times higher risk of nonvaccination compared to
      purebred dogs. The canine-ecology structure is similar to that in regions were
      rabies is endemic.

PMID- 15156996
TI  - A placebo-controlled trial of two intranasal vaccines to prevent
      tracheobronchitis (kennel cough) in dogs entering a humane shelter.
AB  - A placebo-controlled field trial was conducted to compare the effectiveness of
      intranasal (IN) vaccines containing Bordetella bronchiseptica and canine
      parainfluenza virus, with (IN-BPA) or without (IN-BP) canine-adenovirus type 2,
      for prevention of kennel cough at a humane shelter. Dogs were examined on
      admission to the shelter and those without respiratory signs of disease were
      assigned daily, on a rotating basis, to receive one of three vaccines. We
      enrolled 972 healthy dogs. Dogs were monitored for up to 30 days post-vaccination
      for coughing and other clinical signs of respiratory disease. Thirty-three
      (10.7%; 95% confidence interval (CI): 7.2%, 14.2%) dogs in the IN-BP group, 36
      (10.2%; CI: 7.0%, 13.4%) [corrected] dogs in the IN-BPA group, and 42 (13.5%; CI:
      9.7%, 17.3%) [corrected] dogs in the IN-P group coughed spontaneously for > or =
      1 day within 30 days of vaccination (P = 0.37). The IN-BP and IN-BPA vaccines
      were 20.7 and 24.4% effective, respectively, in reducing coughing compared with a
      placebo vaccine. The strongest prognostic factor for coughing (regardless of
      vaccine group) was the number of days spent at the shelter, with each additional
      day increasing the risk of coughing by 3% (95% CI: 1.01, 1.06) [corrected] The
      low incidence of coughing in the shelter during this study precluded observation
      of differences in vaccine effectiveness. No differences in vaccine-associated
      adverse events (coughing, sneezing, nasal or ocular discharge) were noted during
      the first 3 days post-administration or thereafter.

PMID- 15156997
TI  - A mathematical model of the effects of chronic carriers on the within-herd spread
      of contagious bovine pleuropneumonia in an African mixed crop-livestock system.
AB  - Contagious bovine pleuropneumonia (CBPP) is a respiratory disease of cattle; CBPP
      is caused by Mycoplasma mycoides subsp. mycoides small colony. CBPP is a major
      cause for concern for African countries (because of mortality, animal-production
      losses and cost of control). The clinical form of the disease is the more
      infectious (contagion occurs essentially through coughing). However, chronic lung
      lesions with viable mycoplasmas can persist in recovering cattle. Animals
      presenting these lesions might have a time-delimitated infectious phase. Such
      carriers are suspected to generate field outbreaks (although this hypothesis
      remains debated). We investigated the potential quantitative effects of these
      chronic carriers on the within-herd CBPP spread. Data were collected during a
      longitudinal field herd survey in a mixed crop-livestock system in the Ethiopian
      highlands. Two stochastic Markov-chain models' outputs (seroconversion dynamics,
      basic reproduction ratio R0, cumulative clinical incidence and risk of herd
      infection) were compared given different hypotheses on the carrier
      infectiousness. The late seroconversions observed in the field data were fitted
      correctly only for the highest carrier infectiousness we considered (mean chronic
      duration of 1 year and carriers 50-times less infectious than clinical cases).
      Although sensitivities (in terms of disease impact in the herd) were in general
      negligible when the carrier infectiousness was low (e.g. when carriers were
      assumed to be 1000-times less infectious than clinical cases), they rapidly
      became important when the infectiousness increased.

PMID- 15156998
TI  - Relationship between antibodies against Mycobacterium avium subsp.
      paratuberculosis in milk and shape of lactation curves.
AB  - To analyze how infection with Mycobacterium avium subsp. paratuberculosis (MAP)
      affects the shape of lactation curves, a three-level hierarchical test-day model
      was set up with fat-corrected test-day milk yield (FCTM) as response. Milk
      samples from 6955 cows in 108 Danish dairy herds were tested with ELISA to detect
      antibodies against MAP. Optical densities (ODs) recorded on a continuous scale
      were standardized according to parity and stage of lactation. In addition to
      standardized ODs (stOD), seven fixed covariates, quadratic terms and first-order
      interactions were included in the model. Cow and cow nested in herd were included
      as random effects. Cows of first, second and higher parities were analyzed
      separately. The lactation curves after peak yield were significantly less
      persistent in young infected cows, where an increase of one stOD unit was
      associated with a depression of the milk yield per day through day 305 of 3.7 kg
      FCTM in first parity and 2.7 kg FCTM in second parity. In second-parity cows, the
      lactation curve also was both depressed through the entire lactation and more
      steep after 60 days in milk (DIM). In third and older parities, a significant
      effect of the quadratic term of stOD indicated exponentially increased losses
      with increased ODs.

PMID- 15156999
TI  - Comparison of the breeding performance of cows in cold and warm loose-housing
      systems in Finland.
AB  - Finland's cold loose-housing systems for dairy cows were compared with the more
      traditional warm loose-housing systems regarding the number of days from calving
      to-first-service, the first-service-pregnancy risk and the repeated-service
      conception hazard. 3131 calvings registered during the indoor periods in 1996 and
      1997 on 208 farms were modelled using multilevel survival analysis and logistic
      regression in a retrospective cohort study. Compared to cows in a warm loose
      housing system, cows in a cold loose-housing system had the same period from
      calving-to-first-service, a significant 6% lower first-service-pregnancy risk and
      the same repeated-service-conception hazard.

PMID- 15157000
TI  - Epidemiology and burden of illness of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, generally progressive autoimmune disease
      that causes functional disability, significant pain and joint destruction, and
      leads to premature mortality. It is estimated to affect between 0.5 and 1.0% of
      the adult population worldwide, increases in prevalence with age and affects more
      women than men. The magnitude of the severe long-term economic consequences of RA
      has been underestimated in the past. Most patients with the disease require
      continuous treatment to retard or stop progression and to control disease flares.
      Many also require surgery, such as total hip or knee replacement. In addition to
      these direct costs, work disability leads to reduced productivity and early
      retirement, and as a result, substantial indirect costs. The individual and his
      or her family must cope with the feeling of loss of contribution to society
      combined with redefined social roles, and the effects of pain, fatigue, low self
      esteem, mental distress and depression. A number of countries in North America
      and Europe have reported a decline in the incidence of RA in recent years,
      although geographical differences remain that may be associated with genetic,
      environmental or cultural factors. Nevertheless, patients with RA have not shared
      the improvements in survival rates seen with other diseases over the last 40
      years, and have a mean reduction in life expectancy of between 5 and 10 years.
      Disease severity, activity and disability are strongly linked to premature
      mortality in patients with RA. The high direct and indirect costs associated with
      RA, together with the substantial morbidity and mortality affecting millions of
      people worldwide, underline the potential benefits of improved treatments for
      this chronic disease to patients, their families and society.

PMID- 15157001
TI  - Pursuit of optimal outcomes in rheumatoid arthritis.
AB  - The aim of this review is to describe methods of quantifying disease activity and
      symptomatology and discuss treatment goals for rheumatoid arthritis (RA). The
      benefits and limitations of existing therapeutic approaches, the importance of
      early therapy in preventing disease progression and the place of biologicals in
      early therapy will be discussed. Disease activity and symptomatology in RA are
      often measured using a set of core endpoints that incorporate pain, patient
      global assessment, physical disability, swollen joints, tender joints, acute
      phase reactants, physician global assessment and radiographic imaging of joints.
      Imaging of joints is the only means by which to measure the effects of disease
      modifying antirheumatic drugs (DMARDs) on the irreversible joint damage that
      occurs during RA. There is increasing evidence that this damage and its
      functional consequences occur early in the onset of disease. The consensus is
      that patients with RA should be treated with DMARDs earlier rather than later in
      the disease process. Remission, or a state of sustained response or low disease
      activity that is not damaging or disabling, is the ideal goal of therapy for RA,
      but formal criteria defining a state of remission need to be revised and,
      ideally, updated to include a radiographic component. Currently available DMARDs
      are limited in their ability to achieve early, sustained response or remission,
      by delayed onset of action, cumulative toxicity and lack of long-term therapeutic
      response. It is hoped that the emergence of novel DMARDs--targeted biological
      agents, such as anti-tumour necrosis factor-alpha (anti-TNF-alpha)--will help to
      counteract such limitations and will allow early DMARD use to be adopted as
      standard practice in place of their use as a last resort therapy after failure of
      other treatment. One such biological agent, etanercept, has been shown to reduce
      radiographic disease progression and induce overall clinical response during the
      early stages of RA. It is significantly more effective and fast-acting than
      methotrexate, one of the most effective, commonly used DMARDs.

PMID- 15157003
TI  - Drugs that block tumour necrosis factor: experience in patients with rheumatoid
      arthritis.
AB  - Three biological response modifiers that inhibit tumour necrosis factor-alpha
      (TNF-alpha) are approved for treating rheumatoid arthritis (RA). Etanercept is a
      fusion protein comprising two soluble human TNF-alpha receptors linked to the Fc
      fragment of human immunoglobulin G1. Infliximab is a chimeric (human/mouse)
      monoclonal antibody and adalimumab is a humanised monoclonal antibody. In placebo
      controlled trials in established disease-modifying antirheumatic drug (DMARD)
      refractory RA, the anti-TNF-alpha agents have reduced disease activity, as
      monotherapy or in combination with methotrexate. In long-term, open-label studies
      with etanercept or adalimumab, clinical response was sustained for up to 5 years.
      In early RA, etanercept has similar efficacy to methotrexate. However, etanercept
      was more effective than methotrexate in preventing radiographic progression.
      Preventing or delaying disease progression and disability with etanercept therapy
      in early RA may reduce costs associated with long-term disease outcomes. Data
      also suggest a benefit of infliximab plus methotrexate or adalimumab plus
      methotrexate in early RA. All three agents have been shown to improve
      functionality as assessed by health assessment questionnaire (HAQ) disability
      scores. Health-related quality of life is also improved in terms of physical and
      mental health and vitality. Furthermore, etanercept and adalimumab are associated
      with a reduction in fatigue. Long-term etanercept or infliximab therapy is
      associated with increased job employment and etanercept also reduces healthcare
      utilisation. Mild, transient injection-site reactions occur in about 33% of
      patients treated with etanercept and 20% of patients treated with adalimumab. In
      patients treated with infliximab, 16-20% have infusion reactions. The incidence
      of serious infection associated with etanercept and infliximab was low, about 2
      3% in etanercept studies of up to 5 years duration, and 5% in a survey of more
      than 10 infliximab trials. This paper reviews the evidence for efficacy, safety
      and effectiveness of anti-TNF-alpha agents in RA.

PMID- 15157002
TI  - Patient-reported outcomes and their role in the assessment of rheumatoid
      arthritis.
AB  - Patients with rheumatoid arthritis (RA) face considerable physical, social and
      emotional disabilities. In this chronic disease, for which a cure is not yet
      available, improving patients' health-related quality of life (HRQoL) is of the
      utmost concern, particularly as the use of long-term and potentially toxic
      therapy increases. Early HRQoL outcome measures in RA focused on physical
      functioning, but the social and emotional aspects of the disease are now
      increasingly important. Thus, several generic and RA-specific HRQoL instruments
      have been developed, but no one tool covers all areas of HRQoL that affect the
      patient with RA. For this reason, a combination of generic and disease-specific
      tools is currently recommended for RA clinical trials.

PMID- 15157004
TI  - Review of health economics modelling in rheumatoid arthritis.
AB  - As the cost of drug treatment for rheumatoid arthritis (RA) constitutes only a
      small proportion of total costs of the disease to individuals and society,
      therapeutic interventions have the potential for significant economic benefit. To
      take advantage of this potential, clinicians need to gain a global, long-term
      perspective on patient care. Economic evaluations of RA therapies are critically
      important in influencing decisions regarding the role of costly, but highly
      effective new therapies, particularly in settings where there are financial
      constraints on healthcare provisions. Such evaluations, therefore, need to be
      methodologically similar with valid results to enhance their value to clinicians
      and policy decision-makers. This requires the use of appropriate elements in the
      numerator (i.e. total number of dollars spent on healthcare as a result of the
      intervention) and the denominator (net health effectiveness) components of the
      cost-effectiveness equation. Other important design factors also need to be
      managed properly to ensure validity of the evaluation. In this regard, the
      guidelines proposed by the Outcome Measures in Rheumatoid Arthritis Clinical
      Trials (OMERACT) Task Force represent a useful approach to help create common
      standards for economic evaluations in RA. Recently, the development of a number
      of decision analysis models in RA has helped predict the likely cost
      effectiveness of new interventions such as the anti-tumour necrosis factor (TNF)
      alpha agents, etanercept and infliximab, both of which have been found to be cost
      effective relative to other disease-modifying anti-rheumatic drugs (DMARDs) using
      short-term efficacy endpoints. In comparisons of these two agents in patients
      with DMARD-resistant RA, etanercept has been shown to be more cost-effective than
      the combination of methotrexate and infliximab, administered in various dosages,
      over a period of 1 year using American College of Rheumatology (ACR) response
      rates as the primary efficacy measure. However, the criteria for determining
      clinical efficacy is paramount and other studies that use radiographic
      progression as a measure of clinical effectiveness show no difference between
      etanercept and infliximab in clinical efficacy. Important issues that need to be
      considered in developing economic models in RA include consideration of the
      connection between the prevention of radiographic progression and downstream
      economic consequences, and the need to employ lifetime models wherever possible
      because a long time period is necessary to determine the true cost-effectiveness
      of agents that modify radiographic progression of RA, such as etanercept,
      infliximab, and adalimumab. In doing so, it is hoped that such studies will
      provide optimal information to facilitate important decisions on resource
      allocation.

PMID- 15157005
TI  - Brainstem evaluation in children with primary nocturnal enuresis.
AB  - We investigated the brainstem integrity in children with primary nocturnal
      enuresis (PNE) using auditory brainstem responses (ABR), blink reflex and
      exteroceptive suppression of the masseter muscle. We examined 23 children with
      PNE (16 male, 7 female; mean age: 10.4 years) and 19 control subjects (11 male, 8
      female; mean age: 11.8 years). ABR parameters such as wave latencies, amplitudes
      and interpeak latencies and blink reflex parameters such as R1 and R2 amplitude
      and latencies were not significantly different between the 2 groups. Although S2
      parameters of the exteroceptive suppression of the masseter muscle were easily
      and completely obtained from the control subjects, in the PNE group S2 onset
      latency and duration were not recorded in 26% of the study children (n = 6) (P =
      0.01). S2 duration time was significantly lowered in the enuretic group (left
      side: P = 0.001 and right side: P = 0.003). S2 duration time changes in the
      enuretic group supports a possible brainstem dysfunction in children with PNE.

PMID- 15157006
TI  - Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and
      after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema.
AB  - We evaluated the respiratory functions of patients with pulmonary emphysema who
      underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT)
      with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec
      (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the
      Hugh-Jones classification (H-J classification) before and after LVRS. In 69
      patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean
      age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V)
      who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks
      after LVRS and the others 3 months after LVRS) were judged statistically by the
      Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was
      improved with a significant difference (P < 0.05) compared to preoperative
      parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J
      classification at 3 months after LVRS, but was associated with RV and a 6-min
      walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic
      capability after LVRS.

PMID- 15157007
TI  - Frequency in the anomalous origin of the left main coronary artery with
      angiography in a Turkish population.
AB  - We estimated the frequency of anatomic variations in origin of the left coronary
      artery in a Turkish population by analyzing the angiographic data of 10,042
      consecutive adult patients undergoing coronary angiography. Among 10,042 adult
      patients, 5 (0.04%) patients (4 men and 1 woman, age range 40-74, median 58 years
      old) had anomalous origin of the left main coronary artery. The left main
      coronary artery arose from the right coronary sinus of Valsalva in 2 (0.019%)
      patients (both of them had a retro-aortic course), from above the left coronary
      sinus of Valsalva in 2 (0.019%) patients, and from above the non-coronary
      (posterior)-left coronary commisure in 1 (0.009%) patient. Anomalous origin of
      the left main coronary artery is potentially a serious condition, as it can lead
      to myocardial infarction and sudden cardiac death under physical exertion.
      Therefore, greater effort for early detection and surgical repair of this anomaly
      are warranted. The angiographic recognition of anomalous origin of this vessel
      may prove useful for physicians dealing with diagnosis and treatment of anomalies
      of the left main coronary artery.

PMID- 15157008
TI  - Relationship between serum lipid concentrations and posttraumatic stress disorder
      symptoms in soldiers with combat experiences.
AB  - The aim of our study was to assess concentrations of serum cholesterol, low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), and triglycerides in soldiers with combat-related posttraumatic stress
      disorder (PTSD), in comparison with combat-experienced soldiers without PTSD. The
      second aim of our study was to explore the relationship between PTSD symptoms
      such as re-experiencing, avoidance, increased arousal, and serum lipid levels. In
      53 soldiers with combat-related PTSD and 49 with combat experiences without PTSD,
      serum cholesterol, LDL-C, HDL-C, and triglycerides were assayed by an enzyme
      assay method. Soldiers with combat-related PTSD were found to have significantly
      higher concentrations of cholesterol (P = 0.001), LDL-C (P = 0.002), and
      triglycerides (P = 0.001) than soldiers without current PTSD. HDL-C was
      statistically lower (P < 0.001) in soldiers with combat-related PTSD than in
      those without PTSD. A positive correlation was found between increased arousal
      and cholesterol (r = 0.464; P = 0.039), or LDL-C (r = 0.479; P = 0.021)
      concentrations.

PMID- 15157009
TI  - Usefulness of body surface mapping to differentiate patients with Brugada
      syndrome from patients with asymptomatic Brugada syndrome.
AB  - We attempted to determine the usefulness of body surface mapping (BSM) for
      differentiating patients with Brugada syndrome (BS) from patients with
      asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were
      recorded in 7 patients with BS and 35 patients with ABS. Following the
      administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS
      and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were
      compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes
      at J0, J20 and J60 under control conditions were larger in patients with BS than
      in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under
      control conditions in patients with BS showed a higher peak of ST elevation in
      the median precordium compared to that for patients with ABS. Increases in ST
      elevation at J20, J40 and J60 following drug administration were greater in
      patients with BS than in patients with ABS (P < 0.05). Evaluation of the change
      in amplitude of the ST segment at E5 caused by Ic drug administration was also
      useful for differentiating between the 2 groups. In conclusion, BSM was useful
      for differentiating patients with BS from those with ABS.

PMID- 15157010
TI  - Finding the optimal setting of inflated air pressure for a multi-cell air cushion
      for wheelchair patients with spinal cord injury.
AB  - Pressure distribution patterns of the seating interface on the multi-cell air
      cushion (ROHO High Profile) of 36 adults with spinal cord injury (SCI)
      (Neurological level Th3 -L1) were measured at different air pressure levels by a
      pressure mat measurement system. Stress distribution relative to the inflated air
      pressure in the air cushion on the patients' wheelchairs was analyzed to
      determine the appropriate inflated air pressure of the cushion for patients. The
      maximum pressure points in all subjects were at the areas of the ischial
      tuberosities (82 to 347 mmHg). The optimal reduction in interface pressure at the
      ischial tuberosities was obtained just before bottoming out. The cushion air
      pressure at that point was between 17 and 42 mmHg, and correlated well to body
      weight (r = 0.495, P = 0.0021). In contrast, the maximum pressure levels did not
      correlate to body weight or the Body Mass Index (BMI). Pressure at the ischial
      area could be reduced, but not eliminated, by adjusting the air pressure. The
      maximum pressure levels seemed to be related to the shape of the buttocks,
      especially the amount of soft tissue, and exceeded the defined threshold for
      pressure ulcers (> 80 g/cm2).

PMID- 15157012
TI  - Chromosomal instability and double minute chromosomes in a breast cancer patient.
AB  - Cytogenetic analysis was performed in peripheral blood lymphocytes (PBL) of a
      woman with ductal breast carcinoma, who as a hospital employee was exposed
      professionally for 15 years to low doses of ionizing radiation. The most
      important finding after the chemotherapy in combination with radiotherapy was the
      presence of double minutes (DM) chromosomes, in combination with other
      chromosomal abnormalities (on 200 scored metaphases were found 2 chromatid
      breaks, 10 dicentrics, 11 acentric fragments, 2 gaps, and 3 double min
      chromosomes). In a repeated analysis (after 6 months), DM chromosomes were still
      present. To rule out the possibility that the patient was overexposed to ionizing
      radiation at work, her blood test was compared with a group of coworkers as well
      as with a group of professionally unexposed people. The data rejected this
      possibility, but the retroactive analysis showed that the patient even at the
      time of employment had a moderately increased number of chromosomal aberrations
      (3.5%) consisting of 3 isochromatids and 4 gaps, suggesting that her initial
      genomic instability enhanced the later development. The finding of a continuous
      presence of rare DM chromosomes in her PBL (4 and 10 months after
      radiochemotherapy) was considered as an indicator of additional risk, which might
      have some prognostic significance.

PMID- 15157011
TI  - Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients
      with benign prostatic hyperplasia: a prospective non-randomized study of
      loxoprofen sodium 60 mg once daily before sleeping.
AB  - We explored the effectiveness of loxoprofen sodium (loxoprofen), which is the
      most common non-steroidal anti-inflammatory drug (NSAID) in Japan, for patients
      with benign prostatic hyperplasia (BPH) complaining of nocturia. A total of 93
      BPH patients aged 49-84 years were enrolled in the study. These patients had
      received standard drug therapy with alpha1-blocker for BPH, followed by
      anticholinergic drugs, hypnotics, tricyclic antidepressants, and/or antiduretic
      hormone, but they still complained about 2 or more episodes of nocturia. They
      each took a single 60-mg tablet of loxoprofen prior to sleeping at night for 14
      days in addition to their BPH treatments. The effects were assessed by
      questionnaire before and after treatment as excellent (nocturia disappeared or
      decreased by 2 or more voids/night), improved (nocturia decreased by 1
      void/night), unchanged, or worsened (nocturia increased). Nocturia improved or
      disappeared in 74.2% of patients: excellent, improved, unchanged, and worsened
      results were obtained in 37.6%, 36.6%, 21.5%, and 4.3% of patients, respectively.
      The effects were better in patients whose baseline nocturia was > 2 times than in
      those with a lesser frequency at enrollment (P = 0.04). Loxoprofen can be an
      effective and useful treatment option for patients with BPH complaining of
      refractory nocturia.

PMID- 15157013
TI  - Cardiovascular effects of xylazine recorded with telemetry in the dog.
AB  - Cardiovascular effects of xylazine have not been studied with telemetry in dogs.
      In the present study, the effects on cardiovascular parameters after
      intramuscular (i.m.) administration of 2.0 mg/kg xylazine were studied via
      telemetry in unrestrained dogs. Telemetry transmitters were implanted
      subcutaneously (s.c.) with a pressure catheter in the femoral artery.
      Cardiovascular effects and body temperature effects were assessed after i.m.
      administration of xylazine. Heart rate decreased for about 10 min and was
      continuously depressed during 60 min. Thereafter, heart rate slowly increased but
      had not fully reached pre-dose values 4 h after treatment. Both systolic and
      diastolic blood pressure increased immediately after administration of xylazine.
      The systolic blood pressure showed a peak increase for about 5-10 min and then
      decreased below the baseline value not normalizing within 90 min. The diastolic
      blood pressure peaked 5-10 min after xylazine administration but did not return
      to baseline level until 50 min after administration. Body temperature decreased
      continuously for about 90 min and remained low for more than 4 h after treatment.
      An additional administration of xylazine to the same individuals after a recovery
      period of 4 weeks induced exactly the same response in systolic and diastolic
      blood pressure and in heart rate. By using the telemetric recording system it was
      possible to continuously evaluate xylazine-induced cardiovascular responses in a
      way that is not possible with conventional techniques.

PMID- 15157014
TI  - Expression of inflammatory cytokines (TNF-alpha, IL-1, IL-6 and IL-8) in colon of
      pigs naturally infected with Salmonella typhimurium and S. choleraesuis.
AB  - The expression of mRNA encoding tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 (IL-1), IL-6 and IL-8 was studied, by in situ hybridization with a
      non-radioactive digoxigenin-labelled probe, in formalin-fixed, paraffin wax
      embedded colonic tissue from pigs naturally infected with Salmonella typhimurium
      and S. choleraesuis. By in situ hybridization, a distinct positive signal for TNF
      alpha, IL-1, IL-6 and IL-8 was detected in colon from all 12 infected pigs.
      Hybridization signals for all four inflammatory cytokines were detected primarily
      inflammatory cells infiltrating the lamina propria and submucosa. In comparison,
      expression of all four inflammatory cytokines was minimal in non-lesional colon
      of infected pigs and in normal colon from control pigs. The results suggest that
      these cytokines play an important role in the pathophysiological processes in
      porcine salmonellosis.

PMID- 15157015
TI  - Long-term effects of dietary anion-cation balance on acid-base status and bone
      morphology in reproducing ewes.
AB  - The beneficial effects of anionic salts on calcium metabolism have been shown by
      supplementing rations with such salts during the last 3 weeks of pre-partum.
      However, there are few reports on the effects of anionic salts supplementation
      for periods of 4 weeks or longer on acid-base status, mineral metabolism and bone
      morphology. This study was conducted to evaluate the effects of the long-term
      dietary supplementation of anionic salts on the acid-base status, plasma minerals
      concentrations and bone morphology in sheep. Twenty-seven twin-bearing sheep were
      assigned to two experimental groups and a control group, depending on dietary
      cation-anion difference (DCAD) (+272.6, -88.9 and + 164.5 mEq/kg DM,
      respectively). Sheep assigned to each dietary treatment received their respective
      rations beginning 6 weeks prepartum and continuing until 12 days post-partum.
      Diets containing anionic salts induced a mild metabolic hyperchloraemic acidosis
      from 1 week pre-partum to 2 days post-partum that was completely compensated by
      non-respiratory mechanisms. These changes on acid-base status were accompanied by
      an increase of plasma ionized calcium levels. Plasma total calcium, phosphorus
      and magnesium concentrations were not affected by dietary treatment. Parathyroid
      hormone concentrations were related to the concentration of ionized calcium of
      plasma and were higher in sheep fed the cationic diet. Plasma osteocalcin levels
      were increased in sheep fed the anionic diet and cortical bone remodelling
      occurred in all the animals during late pregnancy in light and electron
      microscopy observation, but was particularly evident in the sheep fed the anionic
      diet. Bone turnover might be stimulated because of the role of the bone in
      buffering systemic acidosis. The data suggest that anionic salts ameliorated
      calcium metabolism around parturition by increasing bone resorption and the
      concentration of ionised calcium in plasma, possibly mediated by a mild
      hyperchloraemic metabolic acidosis induced by the salts.

PMID- 15157016
TI  - E-cadherin expression in canine mammary carcinomas with regional lymph node
      metastases.
AB  - E-cadherin (E-cad) is a cell adhesion molecule known for its tumour invasion
      suppressor function. This study investigated the immunohistochemical expression
      of E-cadherin in 19 cases of malignant mammary tumours of the dog and the
      relationship between E-cadherin expression in primary tumours and in regional
      lymph node metastases. E-cadherin expression is not always parallel in the
      primary tumour and in the lymph node metastasis. One year follow-up was available
      in 12 of 19 cases. Three different patterns of expression were revealed in the
      lymph node metastases compared with the primary tumour: downregulation when the
      protein expression was weaker in the metastasis than in the primary tumour;
      upregulation when E-cadherin was stronger in the lymph node than in the primary
      tumour, and a similarly intense expression when it was equal in the metastasis
      and in the tumour. The lymph node pattern revealed a prevalent upregulation or
      downregulation with respect to the primary tumour, whereas a similar expression
      of E-cadherin was encountered in less than 50% of cases.

PMID- 15157017
TI  - Total serum alkaline phosphatase activity in dogs with mammary neoplasms: a
      prospective study on 79 natural cases.
AB  - Increased total alkaline phosphatase (TALP) activity in the serum, long noticed
      in canine mammary tumours among other neoplasms, has not been yet associated with
      malignancy, osseous transformation of neoplastic tissue or histopathological
      typing. Therefore, the purpose of this study was to correlate this biochemical
      abnormality with the above-mentioned parameters, in 79 adult to elderly female
      dogs with mammary neoplasms, without evidence of metastatic or any other disease.
      Histopathology disclosed that 64 (81%) of these neoplasms were malignant and 15
      (19%) benign, belonging to various histological types. Radiology and
      histopathology revealed the presence of osseous tissue in 18 (22.8%) cases. The
      malignant neoplasms were subsequently allocated into group A including 46 (74.2%)
      of epithelial origin and group B with 16 (25.8%) neoplasms of both epithelial and
      mesenchymal origin ('malignant mixed' tumours). In addition, their benign
      counterparts were divided into group C (adenomas, fibroadenomas) and group D
      (benign mixed tumours) that included seven (46.7%) and eight (53.3%) tumours,
      respectively. Almost 55% of the dogs with malignant and 47% with benign tumours
      had increased serum-TALP activity. However, no significant difference in serum
      TALP activity was found between the dogs with malignant (mean +/- SE: 243.7 +/-
      37.4 U/l) and benign (167.9 +/- 38.4 U/l) neoplasms, with (238.9 +/- 45.3 U/l)
      and without (226.5 +/- 38.3 U/l) osseous transformation, with (298.5 +/- 85.6
      U/l) or without (201.2 +/- 30.5 U/l) myoepithelial cell proliferation and with
      different tumour size (T1/T2: 175.1 +/- 34.9 and T3: 254.5 +/- 42.5 U/l). In
      histopathological typing, the only difference noticed involved the malignant
      neoplasms of group A (190.5 +/- 25.5 U/l) compared with group B (378 +/- 124.6
      U/l) dogs. The higher increase of serum-TALP activity in 'malignant mixed'
      tumours could not be attributed to osseous transformation or new ALP isoenzyme
      production by myoepithelial cells. Increased serum-TALP activity is of no
      apparent diagnostic (as to tumour type) or prognostic value.

PMID- 15157019
TI  - Acellular and glutaraldehyde-preserved tendon allografts for reconstruction of
      superficial digital flexor tendon in bovines: Part I--Clinical, radiological and
      angiographical observations.
AB  - Sixteen tenorrhaphies were performed at the mid-metatarsal region in eight
      buffalo calves under lignocaine epidural analgesia. A 2 cm long gap was created
      in the superficial digital flexor (SDF) tendon and immediately repaired with
      acellular grafts in animals of group I, 1% glutaraldehyde-preserved tendon
      allografts in group II. In group III, the defect was repaired with autografts.
      This group served as control. The contralateral limb in each animal was operated
      after an interval of 60 days and the animals underwent the same procedure
      according to the designed groups. Diclofenac sodium and Enrofloxacin was given
      post-operatively for 5 days. Clinical examination revealed significant increase
      (P < 0.05) in rectal temperature, heart and respiratory rate for 3-4
      postoperative days in all the animals. Mild pain and exudation as well as early
      restoration of tendon gliding movements and weight-bearing were observed earlier
      in group I in comparison with group II. Air-tendograms revealed early
      organization, minimal adhesion formation and lesser thickening of tendon at the
      reconstructive site in the acellular group whereas in the glutaraldehyde group
      dense homogenous swelling with adhesions was seen along the flexors. Angiography
      on day 30 showed that the area of proximal and distal host tendon graft junction
      appeared hypervascularized, whereas the area occupied by the graft appeared
      relatively less vascularized. Normal vascularization was observed on day 90 in
      all the three groups.

PMID- 15157018
TI  - Expression of transforming growth factor-beta isoforms in the skin, kidney,
      pancreas and bladder in a German shepherd dog affected by renal
      cystadenocarcinoma and nodular dermatofibrosis.
AB  - The present study was performed to assess the expression of isoforms 1, 2 and 3
      of transforming growth factor (TGF)-beta in skin nodular dermatofibrosis lesions,
      kidney, bladder and pancreas from a 10-year-old female German shepherd dog (GSD)
      affected by renal cystadenocarcinoma and nodular dermatofibrosis (RCND) compared
      with normal GSDs (n = 2). Formalin-fixed, paraffin-embedded tissues obtained from
      the dog affected by RCND, diagnosed by renal ultrasonography and
      histopathological examination were analysed by immunohistochemistry using
      polyclonal antibodies to TGF-beta1, 2 and 3, and evaluated semiquantitatively
      using an immunoreactivity score. Similar expression of TGF-beta2 and TGF-beta3
      was observed in all tissue specimens in both the RCND-affected animal and normal
      dogs. In contrast, TGF-beta1 immunoreactivity was increased in the derma of the
      RCND canine. Comparable TGF-beta1 serum levels were found between the diseased
      and normal animals. The increased local cutaneous production of TGF-beta1 in the
      RCND dog, compared with the normal animals, suggests that this cytokine may play
      an important role in the induction of nodular dermatofibrosis associated with
      renal cystadenocarcinoma.

PMID- 15157020
TI  - Acellular and glutaraldehyde-preserved tendon allografts for reconstruction of
      superficial digital flexor tendon in bovines: Part II--Gross, microscopic and
      scanning electron microscopic observations.
AB  - Sixteen tenorrhaphies were performed at mid-metatarsal region in eight buffalo
      calves. A 2-cm long gap was created in the superficial digital flexor (SDF)
      tendon in all animals. The gap was immediately repaired with acellular grafts in
      animals of group I, 1% glutaraldehyde-preserved tendon allografts in group II,
      and in group III the defect was repaired with autografts (control group). The
      contralateral limb in each animal was operated after an interval of 60 days and
      the animals underwent the same procedure according to the designed groups. Gross
      observation revealed filling of host tendon-graft junction with fibrous
      connective tissue. Increased vascularity was seen in group I when compared with
      group II and III. Graft was resorbed in animals of group I and III, whereas
      partial absorption of graft was seen in group II. Histological observations on
      day 30 revealed restoration of cellularity in acellular graft and fragmentation
      and resorption of glutaraldehyde-preserved graft. Graft was replaced by newly
      formed fibrous connective tissue. Tissue reaction around polygalactin suture
      consisted of plasma cells, lymphocytes and macrophages. On day 90, most of the
      acellular graft was replaced by newly formed fibrous connective tissue. In group
      II the majority of graft portion remained at the site and was in a state of
      resorption. In the control group it was difficult to distinguish between the host
      tendon and the graft. Scanning electron microscopical observation showed densely
      packed neoformed tissue at host tendon-graft junction. Hydrolysis and invasion of
      connective tissue between polygalactin suture filaments, resorption of graft with
      cavity formation and dissolution of ground substance were observed.

PMID- 15157021
TI  - Treatment and follow-up of clinical cyathostominosis in horses.
AB  - The results of the treatment with moxidectin or ivermectin of 20 horses with
      clinical cyathostominosis were studied during a 3-week observation period. Both
      treatments were effective in completely eliminating larvae from the faeces within
      1 or 2 weeks, but no significant improvement in body weight or clinical
      parameters could be demonstrated over the observation period. The poor short time
      results of the treatment support the need for an adequate prevention of
      cyathostominosis in horses.

PMID- 15157022
TI  - Hepatic effects of halothane, isoflurane or sevoflurane anaesthesia in dogs.
AB  - The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic
      function and hepatocellular damage were investigated in dogs, comparing the
      activity of hepatic enzymes and bilirubin concentration in serum. An experimental
      study was designed. Twenty-one clinically normal mongrel dogs were divided into
      three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n
      = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between
      13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre
      anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The
      trachea was intubated and anaesthesia maintained with halothane, isoflurane or
      sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively.
      Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration
      rate, 12-14/min) was started immediately after intubation and the anaesthesia
      lasted for 60 min. Venous blood samples were collected before pre-medication, 24
      and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT)
      activities and bilirubin concentration were measured. Serum AST, ALT and GGT
      activities increased after anaesthesia in all groups. In the halothane group,
      serum AST and ALT activities significantly increased all the time after
      anaesthesia compared with baseline activities. But in the isoflurane group AST
      and ALT activities increased only between 2 and 7 days, and in the sevoflurane
      group 7 days after anaesthesia. GGT activity was increased in the halothane group
      between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after
      anaesthesia. All dogs recovered from anaesthesia without complications and none
      developed clinical signs of hepatic damage within 14 days. The results suggest
      that the use of halothane anaesthesia induces an elevation of serum activities of
      liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days
      after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia
      on the liver in dogs is safer than halothane anaesthesia in dogs.

PMID- 15157023
TI  - Platelets as an innate defence mechanism against Schistosoma mansoni infections
      in mice.
AB  - The interaction between Schistosoma mansoni and platelets of non-immune mice has
      been studied in vivo and in vitro. A moderate thrombocytopaenia was observed in
      mice 2 days after they had been infected percutaneously with 200 cercariae. A
      rabbit anti-mouse platelet antiserum, 25 microL of which injected subcutaneously
      induced a nearly 900% reduction in blood platelet count 24 h later, was used to
      investigate the effects of severe thrombocytopaenia on S. mansoni infections. In
      replicate experiments worm burdens were significantly increased in mice that were
      thrombocytopaenic at the time of infection when compared with untreated mice.
      Induction of thrombocytopaenia on day 4 after infection had no effect on worm
      count. Platelets isolated from non-immune mice were shown to adhere to the
      surfaces of and kill mechanically transformed schistosomula in vitro. Platelets
      may thus be an innate mechanism of defence against schistosome infection, and the
      thrombocytopaenia that occurs during patent schistosome infections may be a
      strategy that helps secondarily incoming parasites evade this type of host
      defensiveness.

PMID- 15157024
TI  - An anti-inflammatory oligopeptide produced by Entamoeba histolytica down
      regulates the expression of pro-inflammatory chemokines.
AB  - Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn
      Ser) with anti-inflammatory properties that, among others, inhibits the in vitro
      and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes
      from this effect [hence the name originally given. Monocyte Locomotion Inhibitory
      Factor (MLIF)]. A synthetic construct of this peptide displays the same effects
      as the native material. We now added MLIF to resting and PMA-stimulated cells of
      a human monocyte cell line and measured the effect upon mRNA and protein
      expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1alpha, MIP-1beta,
      MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The
      constitutive expression of these chemokines and the CC receptors was unaffected,
      whereas induced expression of MIP-1alpha, MIP-1beta, and I-309, and that of the
      CCR1 receptor--all involved in monocyte chemotaxis--was significantly inhibited
      by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not
      only be exerted directly on these cells, but also--and perhaps foremost--through
      a conglomerate down-regulation of endogenous pro-inflammatory chemokines.

PMID- 15157025
TI  - IFN-gamma is associated with risk of Schistosoma japonicum infection in China.
AB  - Before the start of the schistosomiasis transmission season, 129 villagers
      resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi
      Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method
      and 65 negative, were treated with praziquantel. Forty-five days later the 93
      subjects who presented for follow-up were all stool-negative. Blood samples were
      collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and
      soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole
      blood cultures were measured by ELISA. All the subjects were interviewed nine
      times during the subsequent transmission season to estimate the intensity of
      their contact with potentially infective snail habitats, and the subjects were
      all re-screened for S. japonicum by the Kato method at the end of the
      transmission season. Fourteen subjects were found to be infected at that time.
      There was some indication that the risk of infection might be associated with
      gender (with females being at higher risk) and with the intensity of water
      contact, and there was evidence that levels of SEA-induced IFN-gamma production
      were associated with reduced risk of infection.

PMID- 15157026
TI  - The Echinococcus granulosus antigen EgA31: localization during development and
      immunogenic properties.
AB  - EgA31 is a fibrillar protein from Echinococcus granulosus that behaves as a
      potent antigen during infestation of dogs. The localization of this antigen
      during development of the parasite was investigated by immunohistochemistry in
      optical and electron microscopy. The protein is mostly abundant in the
      microtriches and subtegumental cells of the adult, whereas it is absent from
      protoscolex microtriches. Eggs, the periphery of calcareous corpuscles, and the
      germinal layer were other sites of accumulation. Immunogenicity of different
      domains of the protein was assessed during experimental infection of dogs. It was
      shown that the polypeptide encoded by the Pst I-Hind III fragment of the complete
      cDNA is the most antigenic during the infection. The uses of such polypeptide for
      infection diagnosis and as a candidate vaccine protein are discussed.

PMID- 15157027
TI  - Human amoebic hepatic abscess: in situ interactions between trophozoites,
      macrophages, neutrophils and T cells.
AB  - Amoebic liver abscesses (ALA) are the most frequent and severe extraintestinal
      clinical presentations of amoebiasis. During the early establishment of amoebae
      in the liver parenchyma, as well as during the extension of the tissue necrosis,
      parasites interact with the parenchymal liver cells and, as a consequence of
      these interactions, hepatocytes can be destroyed and host immune cells can become
      activated. However, little is known about the nature of these interactions in the
      liver or about the factors involved in the local immune response. In this
      investigation we studied the localization of Entamoeba histolytica trophozoites,
      TCD4+, TCD8+ cells, CD68+ macrophages and CD15+ neutrophils in human ALA using
      immunohistochemical techniques. Trophozoites were found close to undamaged
      hepatocytes in both lysed and non-lysed areas with either sparse or abundant
      inflammatory infiltrate. CD8+ cells were more abundant than CD4+ T cells. CD 68+
      macrophages and CD15+ neutrophils were also detected, suggesting that
      neutrophils, macrophages and T cells might be related to the local host immune
      mechanisms in ALA. We also found that E. histolytica possesses proteins
      recognized by antibodies raised against inducible nitric oxide synthase.

PMID- 15157028
TI  - Identification of CD4+ T cell epitopes of Taenia solium paramyosin.
AB  - T cell mediated response is involved in a protective immune response against
      experimental cysticercosis conferred by immunization with Taenia solium
      paramyosin (TPmy) to BALB/c mice. In this study, we analysed the TPmy amino acid
      sequence for predicted CD4+ T cells epitopes. Five different regions of this
      protein showed that the residues anchor to bind the I-Ad molecule, synthetic
      peptides containing these epitopes were evaluated for their ability to induce
      lymphoproliferative responses of spleen cells from TPmy immunized mice. Among
      them, Tp176 (amino acids 176-192 sequence DDLQRQMADANSAKSRL) was the
      immunodominant T cell epitope of TPmy. Delineation of this epitope should
      facilitate analysis of the role of CD4+ T cell response in experimental
      cysticercosis.

PMID- 15157029
TI  - Infectivity and attenuation of Leishmania donovani promastigotes. II: Association
      of the loss of parasite infectivity with the terminal galactosylation of
      precursor acceptors present in virulent parasites by the developmentally
      regulated galactosyltransferase.
AB  - The beta1-4 galactosyltransferase enzyme of the Leishmania donovani
      promastigotes, was found to be developmentally regulated and expressed only in
      the attenuated parasites. The enzymatic product of soluble determinants of
      virulent promastigotes and the galactosyltransferase enzyme was found to
      stimulate the macrophage burst activity but inhibit in vitro intracellular
      parasitism. In contrast, removal of terminal galactose moieties from soluble
      determinants of attenuated parasites resulted in the inhibition of macrophage
      respiratory burst activity but did not now inhibit intracellular parasitism. We
      propose that the terminal galactosylation of acceptor substrates present in
      virulent parasites by the developmentally regulated galactosyltransferase is
      associated with loss of parasite virulence.

PMID- 15157030
TI  - Radiofrequeny lumbar facet denervation in the elderly.

PMID- 15157031
TI  - Family-peceived distress about appetite loss and bronchial secretion in the
      terminal phase.

PMID- 15157032
TI  - Paracetamol (acetaminophen) allergy.

PMID- 15157033
TI  - Successful treatment of CRPS 1 with anti-TNF.

PMID- 15157035
TI  - Barriers to caregiver administration of pain medication in hospice care.
AB  - Barriers to adequate pain management in hospice and palliative care settings are
      an important area of investigation. In this study, a Caregiver Pain Medicine
      Questionnaire (CPMQ) was developed and psychometrically tested. The CPMQ is a 22
      item self-report instrument that measures concern about reporting pain, concern
      about administering analgesics, and difficulty administering analgesics. One
      hundred fifty-one caregivers of patients admitted to three Chicagoland hospice
      agencies participated; these individuals were family members, hired caregivers in
      the home, or staff nurses in skilled care facilities. While only a small
      percentage of the caregivers expressed concern about communicating information
      about the patient's pain, more than a quarter were concerned about addiction,
      tolerance, and side effects from medications. A fourth of the caregivers had
      difficulty administering medications because of fear of doing something wrong and
      difficulty deciding which or what amount of medications to give. Male caregivers
      and hired caregivers had greater concerns, both about reporting information about
      the patient's pain and administering medications. Greater concerns were also
      evident among less educated caregivers, caregivers who worked in blue-collar
      jobs, and caregivers who were homemakers or retired. Concerns of caregivers in
      the home were significantly greater than staff nurse caregivers in skilled care
      facilities only in the belief that pain could not be controlled and concern about
      addiction. Caregivers who had greater concern about addiction and tolerance, and
      more difficulty administering medications, rated the patient's pain as less
      completely controlled. These findings remind hospice staff members of the
      importance of assessing specific caregiver concerns about medication
      administration and devising appropriate strategies to address them.

PMID- 15157034
TI  - Pain characteristics and treatment outcome for advanced cancer patients during
      the first week of specialized palliative care.
AB  - To examine pain in cancer patients referred for specialized palliative care, we
      described pain characteristics and medication on admission, examined changes in
      pain during the first week, and searched for predictors of initial pain intensity
      and treatment outcome. On arrival in the department (T0) and after one week (T1),
      pain was evaluated with the Edmonton Symptom Assessment System (ESAS) and EORTC
      QLQ-C30. Analgesics were recorded. We investigated the associations between
      initial pain scores as well as differences from T0 to T1, and clinical and
      sociodemographic parameters, initial medication, and medical interventions. Of
      267 eligible patients, initial pain scores were obtained from 175. Initial pain
      scores were high, although 81% of patients received opioid treatment at T0. Bone
      metastases, neuropathic pain, mixed pain pathophysiology, and breakthrough pain
      were associated with higher initial pain scores. Pain scores decreased during the
      first week. No single parameter convincingly predicted a better or worse outcome
      of pain treatment.

PMID- 15157036
TI  - End-of-life care in urban areas of China: a survey of 60 oncology clinicians.
AB  - Although cancer is a leading cause of death, little is known about cancer-related
      end-of-life care in China. We surveyed 60 Chinese oncology clinicians' practices
      and attitudes toward end-of-life care. Fewer than half reported available
      hospital-based hospice service, although mast urban cancer patients die in the
      hospital. Most clinicians reported they felt competent to care for dying patients
      -more competent in controlling pain, constipation, nausea, and vomiting, but less
      competent in managing depression, anorexia, and dyspnea. Regarding disclosure,
      most believed that patients should know and want to know their diagnosis and
      stage, whereas families strongly resist informing patients. Unrealistic family
      expectations, fears of depressing patients, and physician reluctance to stop
      treatment were barriers to disclosing prognosis to patients, to ending anti
      cancer therapy, and to starting palliative care. Results of the survey suggest
      specific training and research in symptom management that might improve end-of
      life care for Chinese cancer patients.

PMID- 15157037
TI  - Evaluation of efficacy of the perioperative administration of venlafaxine XR in
      the prevention of postmastectomy pain syndrome.
AB  - Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that may
      develop following breast surgery. Venlafaxine has been shown to be efficacious in
      the management of PMPS. The preemptive administration of venlafaxine has been
      shown to be efficacious in reducing the incidence of neuropathic pain in the rat
      model. We examined the efficacy of administering either venlafaxine or placebo
      for two weeks starting the night before surgery to 100 patients scheduled for
      either partial or radical mastectomy with axillary dissection. Patients were
      administered PCA morphine for the first 24 hours following surgery and then
      acetaminophen/oxycodone tablets. Pain scores were recorded at rest and movement
      on day 1, at 1 month, and at 6 months after surgery. At 6 months postoperatively,
      the presence of pain in the chest, arm, and axilla; edema; decreased sensation in
      the operative area; and phantom breast pain were recorded. There was no
      difference in postoperative opioid use. Pain scores with movement were lower in
      the venlafaxine group at 6 months. Pain scores at all other time intervals were
      similar. There was a significant decrease in the incidence of chest wall pain
      (55% vs. 19%, P = 0.0002), arm pain (45% vs. 17%, P = 0.003), and axilla pain
      (51% vs. 19%, P = 0.0009) between the control group and the venlafaxine group,
      respectively. No significant differences were noted between the two groups with
      regard to edema, phantom pain, or sensory changes. We conclude that the
      perioperative administration of venlafaxine beginning the night prior to surgery
      significantly reduces the incidence of PMPS following breast cancer surgery.

PMID- 15157038
TI  - Psychometric evaluation of the Pittsburgh Sleep Quality Index in cancer patients.
AB  - This report summarizes findings related to the psychometric properties (internal
      consistency and construct validity) of the Pittsburgh Sleep Quality Index (PSQI)
      and discusses issues related to its use based on data from two clinical studies
      with diverse samples of cancer patients. Subjects completed a questionnaire that
      included the PSQI, the Schwartz Cancer Fatigue Scale, and specific demographic,
      disease, and treatment variables. There were complete data on 170 (of 214) cases
      in Study 1 and 249 (of 259) cases in Study 2. The Cronbach's alpha for the Global
      Sleep Quality scale was 0.81 in Study 1 and 0.77 in Study 2 A comparison of
      Global Sleep Quality in two contrasting groups with low and high fatigue yielded
      statistically significant differences in both samples. Psychometric evaluation
      supports its internal consistency reliability and construct validity. However,
      the scoring is rather cumbersome and raises questions regarding level of
      measurement and appropriate analysis techniques.

PMID- 15157039
TI  - Gender differences in the perception of chest pain.
AB  - This study investigated gender differences in pain perception as characterized by
      pain symptoms in patients diagnosed with unstable angina pectoris. Twenty-nine
      women and 32 men were asked to characterize their chest pain using a semi-open
      questionnaire assessing pain intensity (by numerical rating), pain location, pain
      characteristics, complaints following chest pain, factors that evoked or reduced
      chest pain, and whether the chest pain was related to heart disease. Significant
      gender differences were found. Women scored the intensity of their chest pain
      significantly higher than men (Chi-square 14.8, P < 0.0001), and related their
      chest pain less to heart disease (Chi-square 24.6, P < 0.0001). The women
      described an atypical clinical picture of chest pain that was significantly
      different from men's. The results are discussed in light of pschological theories
      regarding gender differences in pain perception. These findings imply the need
      for special attention to the unique clinical pictures that appear for women and
      men.

PMID- 15157040
TI  - Understanding the causes of problematic pain management in sickle cell disease:
      evidence that pseudoaddiction plays a more important role than genuine analgesic
      dependence.
AB  - Treatment of painful episodes in sickle cell disease (SCD) is sometimes
      complicated by disputes between patients and staff and patient behaviors that
      raise concerns about analgesic misuse. Those concern-raising behaviors could
      indicate either drug seeking caused by analgesic dependence or pseudoaddiction
      caused by undertreatment of pain. To make a systematic assessment of concern
      raising behaviors and examine their associations with other factors, including
      DSM-IV symptoms of substance dependence, individual, in-depth interviews with SCD
      patients were conducted to apply pre-established criteria for concern-raising
      behaviors. These included disputes with staff tampering with analgesic delivery
      systems, passing prescribed analgesics from one person to another, being
      suspected or accused of analgesic misuse, self-discharging from hospital,
      obtaining analgesic prescriptions from multiple sources, using illicit drugs, and
      injecting analgesics. Assessments were also made of pain-related symptoms of
      substance dependence (where behaviors resemble substance dependence but reflect
      attempts to manage pain, increasing the risk of pseudoaddiction), non-pain
      related symptoms of substance dependence (where substance dependence reflects
      analgesic use beyond pain management), and pain coping strategies (using the Pain
      Coping Strategies Questionnaire). Inter-rater reliability for the assessment of
      concern-raising behaviors was high, with Kappa coefficients of 0.63 to 1.0. The
      most frequent concern-raising behaviors were disputes with staff about pain or
      analgesics. The least frequent were tampering with analgesic delivery systems and
      passing analgesics between patients in hospital. The odds of concern-raising
      behaviors in hospital were raised eightfold by less use of ignoring pain as a
      coping strategy, and more than doubled by each additional pain-related symptom of
      substance dependence. Non-pain-related symptoms of substance dependence had no
      independent effect on concern-raising behaviors. Concern-raising behaviors were
      more closely associated with pain behaviors that make patients vulnerable to
      misperceptions of substance dependence than they were with genuine substance
      dependence. The results show how pseudoaddiction can adversely influence hospital
      pain management, and suggest that more emphasis should be placed on patients'
      pain and analgesic needs when responding to concern-raising behaviors in
      hospital.

PMID- 15157041
TI  - Foundations of knowledge about neonatal pain.
AB  - This review appraises trends in the neonatal pain research literature. We
      searched the literature produced from 1941 to 2001. Information about the model
      of pain, measures of pain, design, and sample characteristics is included for
      each citation. Gaps in knowledge are attributed to specific conceptual and
      methodological problems, including the lack of basic knowledge about pain
      behavior, over-reliance on an invasive short-term pain model, pain measurement
      issues, and lack of knowledge about confounders. Ethological research methods
      could be used to expand basic knowledge about newborn pain.

PMID- 15157042
TI  - What has dry cough in common with pruritus? Treatment of dry cough with
      paroxetine.
AB  - Distressing persistent dry cough is commonly the consequence of sensitization of
      the cough reflex. A slight and transient peripheral nociceptive impulse, such as
      bronchitis, may be perpetuated for weeks because of sensitization of the cough
      reflex. Cough usually can be inhibited by opioids, but some types of cough can be
      out of opioid control or even be induced by opioids. We describe here a series of
      5 patients with dry cough that did not respond to codeine. Because two of these
      patients also suffered with pruritus, paroxetine was tried. In all patients,
      cough ceased within hours to days. The only observed adverse effect was
      sleepiness in the first days of therapy. Paroxetine should be investigated as
      antitussive in cases of opioid-resistant cough. The putative mechanism of action
      of paroxetine on pruritus and rough is discussed.

PMID- 15157043
TI  - The decision to prematurely terminate a trial of R-HuEPO due to thrombotic
      events.
AB  - Recombinant human erythropoietin (r-HuEPO) corrects cancer-related anemia and,
      thereby, improves quality of life. The purpose of the present study was to
      measure the impact of erythropoietin on hemoglobin and mood state in patients
      with metastatic breast cancer and mild anemia (Hgb < 12.0 g/dL). Women were
      randomized to receive usual care (G1) or usual care plus r-HuEPO (G2). Usual care
      included transfusions as necessary and fatigue education. R-HuEPO was begun at
      40,000U subcutaneously per week. At 4 weeks, the dose was increased to 60,000U if
      Hgb had not increased > or = 1.0 g/dL. The drug was discontinued at 8 weeks if
      hemoglobin improvement was < 1.0 g/dL. The study was terminated early (n = 27, G1
      = 13, G2 = 14) when 4/14 (28.5%) subjects in G2 developed thrombotic events (deep
      vein thrombosis [DVT] in 1; DVT plus pulmonary embolism [PE] in 1; DVT plus PE 1
      month after drug discontinuation in 1; and brachial vein thrombosis with infected
      Mediport in 1). In all four patients, Hgb levels were normal at the time of the
      event. No patient in G1 developed a thrombotic event. There were no significant
      differences in demographic characteristics or current chemotherapy regimen in G1
      vs. G2. The decision to terminate the trial was made after considerable
      deliberation. The increased incidence of thrombotic events in the r-HuEPO (G2)
      arm of this study exceeds that in prior studies in this population and prior r
      HuEPO trials. This may relate to the administration of r-HuEPO in this high-risk
      population, but the small sample size and possible predisposing risk factors
      preclude definitive conclusions.

PMID- 15157044
TI  - Loss of SMAD4 function in small intestinal adenocarcinomas: comparison of genetic
      and immunohistochemical findings.
AB  - Despite morphological similarities between adenocarcinomas of the small and the
      large intestine, recent evidence suggests that both tumor types follow different
      genetic pathways. In particular, inactivation of the APC tumor suppressor gene, a
      characteristic alteration of colorectal carcinomas, does not seem to play a
      significant role in sporadic small intestinal tumorigenesis. We could recently
      show that inactivating mutations of the SMAD4 gene frequently occur in small
      intestinal adenocarcinomas. To further elucidate the role of SMAD4 dysfunction
      for tumor development in the small intestine, we immunohistochemically analyzed
      20 sporadic, non-ampullary carcinomas for the expression of the SMAD4 protein. We
      further determined homozygous SMAD4 gene deletions by real time PCR and compared
      SMAD4 immunohistochemical data with SMAD4 genetic data. Immunohistochemistry was
      negative for the tumor cells in two (10%) cases and strongly reduced in four
      (20%). Negative immunohistochemical staining corresponded with homozygous gene
      deletions. A regular or only slightly reduced staining pattern was noted in 14
      carcinomas, including four tumors with previously identified SMAD4 missense and
      frame shift mutations. In conclusion, our data suggest a significant role of
      impaired SMAD4 function in the pathogenesis of small intestinal adenocarcinomas.
      Furthermore, our results show that SMAD4 immunohistochemistry may serve as a
      surrogate for analysis of homozygous gene deletions. However, the method fails to
      identify SMAD4 inactivation due to missense mutations.

PMID- 15157045
TI  - Biopathological profile of multiple synchronous homolateral and bilateral breast
      cancers.
AB  - It still needs to be verified whether multiple syncronous homolateral and
      bilateral breast cancers represent intramammary spread of a single tumor or two
      or more separate neoplastic events. To clarify this problem, we studied the
      biopathological profile of 46 homolateral and 20 bilateral cases. The cancers
      were always surgically removed and processed at the same time. The expression of
      estrogen receptors (ER), progesterone receptors (PR), MIB 1, p53, and c-erbB-2
      was determined. Computer-assisted image analysis (CAS 200) was used to evaluate
      ER, PR, MIB 1, and p53. The histological concordance was 95.6% in homolateral and
      50% in bilateral cases. The immunophenotype profile of multiple homolateral
      neoplasms showed a concordance between 93.47% for ER and 78.26% for p53. The
      results were statistically significant for all parameters except for p53. In
      bilateral cancers, there was a significant statistical concordance for ER. These
      data strongly suggest that both mechanisms may exert an influence and, in
      particular, that in the majority of homolateral carcinomas, there may be
      intramammary spread of tumor cells. In multiple bilateral tumors, however, the
      great diversity of the histological aspects and the differences in the
      immunophenotype pattern suggest that the vast majority of these may constitute
      independent multiple events.

PMID- 15157046
TI  - Nuclear markers (star volume, mitotic index, AgNOR and Ki-67) of the primary
      tumor and its metastasis in non-small cell lung carcinomas.
AB  - Although tumor growth is controlled by growth rate and cell cycle, it is also
      likely that the proliferative activity of tumor cells can influence the growth
      rate of the primary cancer and account for their aggressiveness. Variations in
      growth rate, cell cycle control and proliferative activity could, in part,
      explain differences in invasive and metastatic properties among non-small cell
      lung carcinomas (NSLC). The purpose of this report is to: (1) evaluate growth
      rate by using growth- and cell cycle-regulating markers (mitotic count, nuclear
      star volume, AgNOR, and Ki-67) as reflections of growth rate and (2) compare the
      indices of primary NSLC with the indices of their metastasis in a series of
      patients with advanced disease. Thirty-three patients with non-small cell lung
      cancer and hematogenous metastases were retrospectively studied by histochemical,
      immunohistochemical, and morphometrical investigations. Clinical variables were
      examined for differences in the frequency of histological subtypes, nuclear star
      volume, mitotic index, AgNOR area, and Ki-67 immunohistochemistry indices of
      expression in subgroups of patients stratified by primary tumor and hematogenic
      metastasis. The impact of these factors on overall follow-up was analyzed. In the
      samples available in this study, consisting of primary-met paired tumors, which
      are unique and rarely available for studies of lung cancer, we found that nuclear
      star volume and mitotic index in metastatic tumors were significantly higher than
      in the primary tumors. Although there was no significant difference between the
      Ki-67 index of metastatic and primary tumors, the Ki-67 index in metastatic brain
      tumors was significantly higher than in the corresponding primary tumors.
      Examination of Kaplan-Meier survival curves demonstrated that patients with
      metastatic tumors showing AgNOR area higher than 10.82 microm2 and nuclear star
      volume lower than 559.50 microm3 had approximately the same odds ratio (log rank
      of 4.16 and 3.25, p = 0.04 and 0.01, respectively) for survival with a median
      survival time equal to 17 months for both groups. Analysis of the remaining
      marker correlation had no impact on survival. We conclude that these results
      offer future possibilities for more complex studies, including the results of
      additional immunohistochemical analysis using molecular markers that are known to
      be important in regulating cell proliferation, e.g., cyclin D1, p27, and cyclin
      E. These would influence clinical decisions or different therapeutic approaches
      in advanced stage disease of non-small cell lung cancer.

PMID- 15157047
TI  - Immunohistochemical and in situ detection of cytomegalovirus in lung autopsies of
      children immunocompromised by secondary interstitial pneumonia.
AB  - Secondary interstitial pneumonia (SIP), a disease affecting patients
      immunocompromised by primary underlying diseases during their treatment in
      hospital, is frequently associated with cytomegalovirus (CMV) infection, a
      potentially treatable condition. However, in many cases, no infectious agent can
      be determined, and this clinical disease rapidly progresses to death.
      Theoretically, SIP could be caused by CMV, which may be present in such small
      amounts or such configuration that routine histopathological analysis or viral
      culture techniques cannot detect the virus. To test the hypothesis that
      immunohistochemistry (IH) and in situ detection by hybridization (ISH) provides
      more accurate results than the mere histological demonstration of CMV inclusions,
      these methods were applied to 37 autopsied lung sections obtained from children
      immunocompromised by primary underlying diseases and who died of SIP. As a
      result, the cases were subdivided into three groups: (1) children with SIP CMV
      inclusions (Diffuse alveolar damage-DAD-related) (n = 7); (2) children with SIP
      without classical viral inclusions (CMV-DAD-related) (n = 3); (3) children with
      SIP exhibiting nuclear cytopathic effect (not CMV-NSIP-related) (n = 27). In the
      first group, all three techniques yielded clearly positive results, whereas IH
      and ISH indicated that three of the children of the second group had CMV-related
      DAD without histological demonstration of CMV inclusions. In the third group,
      there were no positive CMV signals. These data indicate that DAD-related CMV
      infection is an important cause of SIP and of death in children immunosuppressed
      by primary underlying diseases, and that IH and in situ detection were more
      sensitive than the histological demonstration of CMV inclusions. A direct
      involvement of CMV in SIP exhibiting DAD is likely, but not in the non-specific
      interstitial pneumonia (NSIP) pattern. We conclude that all children with primary
      underlying diseases should be investigated for CMV SIP using sensitive IH and in
      situ tests in conjunction with histological routine procedures.

PMID- 15157048
TI  - Reduction of procarbazine-induced cleft palates by prenatal folic acid
      supplementation in rats.
AB  - We investigated the effects of prenatal folic acid supplementation on
      procarbazine (PCZ)-induced intra-uterine growth retardation (IUGR), cleft
      palates, and microgenia. Three groups of gravid rats were treated with 200 mg/kg
      body weight (BW) PCZ on day 13.5 of gestation (GD13.5). Two groups of them were
      additionally supplemented with 1 and 2.5 mg/kg folic acid, respectively, from
      GD13.5 through GD16.5. On GD19.5, all fetuses were delivered by caesarian
      sections and sexed subsequently. Numbers of live and dead fetuses as well as
      resorptions were counted. Data on fetal BW, crown-rump length, tail length,
      placental weight, and diameter were collected. Fetal heads were histologically
      scrutinized for the occurrence of cleft palates and microgenia. Folic acid at 2.5
      mg/kg diminished PCZ-induced IUGR. In male fetuses, both folic acid doses
      significantly reduced the incidence of cleft palates and microgenia, while in
      females, only the high folic acid dose was capable of lowering the occurrence
      frequency of cleft palates. We conclude that folic acid supplementation at the
      used doses confers a substantial protection against PCZ-induced IUGR and
      incidence of cleft palates and microgenia. However, these effects are gender
      related and dose-dependent.

PMID- 15157049
TI  - Vacuole formation in the endothelium of rat extremity vessels depends on fixation
      techniques and vessel type.
AB  - Applying immersion fixation for electron microscopy, huge clear endothelial
      membrane-bound vacuoles of 0.1-3 microm diameter were noted in the extremity
      veins of Sprague-Dawley rats. Histological and electron microscopic histochemical
      methods were applied to determine whether they were the product of programmed
      cell death or any other kind of cell damage. Image analyzer was used to measure
      the total area of the vacuoles in the endothelium cells. Neither lipid content
      nor acidic phosphatase activity could be identified in the vacuoles. In saphenous
      and brachial veins, the vacuoles occupied 20.6 +/- 2.21% and 18 +/- 2.45% of the
      endothelium, respectively. Venous endothelium of two different strains of rat
      also contained the vacuoles. No such structures appeared in extremity arteries.
      Long-term tilting did not influence vacuolization. Using in vivo whole body
      fixation, only pinocytotic and dense microvesicles, but no vacuoles were noted.
      In conclusion, the clear vacuolar structures represent neither lipid inclusions
      nor secondary lysosomes. The method of tissue fixation is critical when venous
      endothelial vesicles are investigated. It is presumed that the vacuoles
      originated from intra- or intercellular microstructures, and that in case of the
      collapsible vein segments, their size is increased under the pathological-hypoxic
      and low-pressure-conditions of in vitro fixation.

PMID- 15157050
TI  - Atypical lymphocytosis resembling non-Hodgkin's lymphoma in peritoneal effusion
      of infectious mononucleosis: a case report.
AB  - Peritoneal effusion appears to be an unusual complication of infectious
      mononucleosis (IM). The cytological features of peritoneal effusion from a
      patient affected by IM are presented. The patient was a 21-year-old Japanese
      woman, with typical and physical findings of IM. Ascites disappeared with
      resolution of acute IM. The cytospin smears of the ascitic fluid were highly
      cellular, consisting exclusively of lymphoid cells. Lymphoid cells were composed
      of large cells with broad basophilic cytoplasm, as well as of small to medium
      sized cells having scant cytoplasm and irregularly shaped nuclei. The overall
      cytomorphological pictures posed serious difficulties in differentiating this
      condition from those of peripheral T-cell lymphomas manifesting ascites. The
      majority of atypical lymphocytes, including large cells, expressed CD3 and CD8.
      The present case indicates that IM should be added to the list of lesions
      considered for the differential diagnosis of non-Hodgkin's lymphoma of the
      peritoneal fluid, particularly regarding young adults.

PMID- 15157052
TI  - Demonstration of MyoD1 expression in oncocytic cardiomyopathy: report of two
      cases and review of the literature.
AB  - Oncocytic cardiomyopathy is a rare arrhythmogenic disorder usually associated
      with female sex, difficult-to-control arrhythmias, or sudden death of infants and
      children. Morphologically, it is characterized by the presence of oncocytic
      cells, which are diffusely distributed or form the nodular structures within the
      myocardium, occasionally involving the valves, with a large number of
      mitochondria in cytoplasms. We present two cases of oncocytic cardiomyopathy. The
      first case had a fatal clinical outcome, and the other case was surgically
      treated. The nuclear expression of skeletal muscle transcription factor MyoD1 was
      demonstrated in the first case, supporting the theory that oncocytic
      cardiomyopathy is a conduction system developmental disorder. To confirm this
      hypothesis, it is necessary to further investigate myogenic transcription factor
      program in human cardiac conduction system cells.

PMID- 15157051
TI  - Lymph node lesion in infectious mononucleosis showing geographic necrosis
      containing cytologically atypically B-cells. A case report.
AB  - Lymph node lesions in infectious mononucleosis (IM) show a marked histological
      diversity and may occasionally be confused with malignant lymphoma. We report on
      a rare case of IM showing geographic lymph node necrosis as well as angiocentric
      lymphoproliferative lesions, and containing numerous centroblasts, immunoblasts
      and Reed-Sternberg (RS)-like cells. The patient was a 40-year-old Japanese man
      with signs and symptoms of classical IM. This was later confirmed serologically,
      but the necrotic area comprised 50% of a cervical lymph node. The large lymphoid
      cells, including RS-like cells, were CD3-, CD5-, CD15-, CD20+, CD30+, CD45RO-,
      CD79a+, LMPI+, and EBNA2+. In situ hybridization study also disclosed that these
      cells were associated with Epstein-Barr virus (EBV). The patient was disease free
      during a follow-up of 15 years. Although the classical IM syndrome rarely shows a
      close resemblance to lymphomatoid granulomatosis of the lymph node or to EBV+ B-
      cell lymphoproliferative disorders associated with an immunodeficient state on
      histology, it is important for pathologists to be aware of this type of lesion in
      diagnostic practice.

PMID- 15157053
TI  - A different perspective on care of the special needs patient: the UK model.

PMID- 15157054
TI  - Developmental stuttering: manifestations, treatment and dental implications.
AB  - Developmental stuttering (DS) is a disturbance in the normal fluency and time
      patterning of speech resulting in involuntary repetition, prolongation, or
      cessation of sound. The scientific literature has implicated the lack of strong
      left cerebral dominance and abnormal levels of the neurotransmitters dopamine and
      possibly serotonin in regions of the brain controlling the coordination of
      language processing and motor activity of the vocal apparatus as possible
      causative factors in DS. Speech-language therapy is the most common form of
      treatment, but antipsychotic, antidepressant, and anxiolytic medications may be
      prescribed for some children and adults with persistent stuttering. These
      medications may cause xerostomia and adversely interact with certain antibiotics,
      analgesics, and sedatives routinely used in dentistry. Some people who stutter
      have sensory-motor and tactile-proprioceptive deficits that impede accurate and
      timely movements of the mandible, lips, and tongue, necessitating protection of
      the airway by staff during dental care.

PMID- 15157055
TI  - Oral health: perceptions of need in a rural Iowa county.
AB  - Several studies have shown that oral health problems impact the quality of life
      of older adults. However, few data are available to describe the oral health
      status, barriers to care, and patterns of care for adults and older populations
      living in rural areas. The purpose of this study was to evaluate the perceived
      need for treatment of oral health problems by adult residents in a rural county
      in Iowa. The oral health component was part of a larger longitudinal health study
      of the residents. The sample was stratified into three groups by residence, that
      is, farm households, rural non-farm households and town households. The sample
      was subsequently post-stratified by gender and age group into young elderly, 65
      74 years old, and old elderly, 75 years and older. Dentition status varied
      according to age and was related to the perception of treatment needs. Edentulous
      persons had fewer perceived treatment needs and utilized a dentist less
      frequently. Place of residence, education, and marital status were not associated
      with the subjects' perceived problems with eating and chewing. However, persons
      with difficulty chewing were more likely to have some missing upper teeth, have a
      perceived need to have denture work, and have smoked for a number of years. The
      results suggest that this rural population is retaining more teeth and
      consequently may need and may seek dental services more often than previous more
      edentulous cohorts.

PMID- 15157056
TI  - Clinical evaluation of patients with epidermolysis bullosa: review of the
      literature and case reports.
AB  - Epidermolysis bullosa (EB) is a relatively rare inherited disorder, which
      includes blister and vesicle formation on the skin and mucous membranes as a
      result of trauma or heat. There are different forms of this disorder. Mild
      manifestations are relatively uncomfortable, usually involving the knees, elbows,
      and fingers. Severe forms of this disease compromise normal functioning of
      multiple organs, which may result in premature death. The lack of a specific
      treatment to cure EB makes genetic counseling and prenatal diagnosis of primary
      importance to control this disorder. Three case histories of persons with
      dystrophic recessive epidermolysis bullosa are reported, focusing on appropriate
      dental care for patients with EB.

PMID- 15157057
TI  - Evaluation of Class I ART restorations in Brazilian schoolchildren: three-year
      results.
AB  - Atraumatic Restorative Treatment (ART) has been adopted around the world to avoid
      unnecessary extractions, especially in non-industrialized countries. The
      development of specific glass ionomer cements marketed for the ART technique has
      contributed to the technical success rate. In this study, Ketac-Molar (3M ESPE,
      Dental Medzin, Germany) was used to restore 150 Class I cavities in 118 Brazilian
      public school children, aged from 7-12 years. At baseline and at subsequent
      recalls, CPI probes with a ball-end of 0.5 millimeters (mm) were used to assess
      loss of restorative material, and photographic color transparencies of
      restorations were made. After six months, 83 patients returned for follow-up
      examinations, with 71.8% of their restorations designated as acceptable. After
      three years, 49 patients with 57 ART-restorations were evaluated, with 21.0% of
      these restorations graded as acceptable. Another 29.8% of their restorations had
      been replaced by more permanent materials. The main objective of the ART
      technique is tooth retention; this was achieved for 94.7% of the restored teeth
      in a high caries risk population who returned for recalls.

PMID- 15157058
TI  - [Humanizing the announcement of cancer].

PMID- 15157059
TI  - [Hypertensive crisis: when and how to treat?].
AB  - A hypertensive emergency is a situation in which uncontrolled hypertension is
      associated with acute end-organ damage, such as aortic dissection, pulmonary
      edema, acute coronary syndromes, cerebral infarction or hemorrhage, hypertensive
      encephalopathy, acute renal failure and eclampsia. With the exception of stroke,
      blood pressure must be reduced quickly, usually by using intravenous
      antihypertensive agents. Blood pressure reduction should be gradual while
      maintaining organ perfusion, which may be easily compromised in elderly and
      chronically hypertensive patients. In the absence of new or worsening end-organ
      injury, the indication of immediate therapy should be carefully evaluated. If
      indicated, the use of an orally long-acting antihypertensive agent is preferred
      to avoid an acute and unpredictable fall in blood pressure. In particular, the
      use of short-acting nifedipine should be condemned.

PMID- 15157060
TI  - [Cardiac magnetic resonance. Myth and reality].
AB  - The authors report their own experience and a review of the current literature in
      the field of cardiac MR (CMR). Latest technical improvements now allow obtaining
      both anatomical and functional imaging of the beating heart and great vessels in
      most pathological conditions. Established CMR indications such as cardiac tumors,
      pericardial diseases, operated congenital heart diseases, valvular diseases,
      arythmogenic right ventricular dysplasia, specific cardiomyopathies and great
      vessels of the thorax are reviewed and updated. Current applications in post
      myocardial infarction such as perfusion and viability imaging sequences are
      described. Moreover, CMR applications in syndrome X and myocarditis are evoked.
      Medical contra-indications and technical limitations of CMR are also discussed.
      Finally, the authors insist on the interest of a real partnership between
      radiologists and cardiologists for these procedures.

PMID- 15157061
TI  - [Cannabis: experts agree more than they admit].
AB  - Cannabis is evermore present in society, whether within the general public or as
      a subject for scientific debate. Mass consumption of cannabis, for example, is
      stabilising around 22 percent of 18-year old who admit to having used it at least
      once during the previous month; however, this consumption rate falls off as they
      enter later adulthood. This article describes the emerging scientific consensus
      about the effects of this drug. The psychotropic effects of cannabis--the result
      of cannabinoids contained in its resin that activate specific receptors--include
      general euphoria, a mild release from inhibitions and, in certain cases, some
      distortion of sensory perception. Some patients also experience drowsiness, a
      stimulated appetite and anxiolysis, while others anticipate a more intense
      experience such as an altered state of consciousness. The toxicity of smoked
      cannabis and its acute, chronic secondary effects are described, as well as the
      problematic relationship between cannabis consumption and psychosis. The damages
      and toxic effects attributed to such consumption are presented via three, related
      themes: the growth of dependency, negative somatic consequences (including
      cognitive impairment and its consequences for driving an automobile, and damaging
      psychosocial effects. "Escalation theory" is criticized. In their conclusion, the
      authors cast doubt on the scientific grounds for penalisation of cannabis
      consumption, and recommend a "de-demonisation" of the drug. An analysis and
      discussion of the current penalties applied in Belgium are presented.

PMID- 15157063
TI  - [Tuberculous sacroiliitis: report of a case].
AB  - Our case concerns a 32-year old Cameroonian male presenting with tuberculous
      sacroiliitis. Diagnosis was made on the basis of a positive abscess needle
      aspirate. Tuberculous sacroiliitis is rare and generally an isolated phenomenon.
      Its insidious presentation leads to delayed diagnosis. The affection is often
      overlooked due to lack of awareness of the clinicians, the usually good condition
      of the patient and minimal signs of sacroiliac joint infection. Haematological
      data are frequently non contributory. High risk groups include developing
      countries immigrants, immunodepressed patients and low socioeconomic status.
      Accurate diagnosis is based on percutaneous synovial fluid or abscess aspirate
      bacteriology. CT-scan and NMR are the most helpful radiological examinations.

PMID- 15157062
TI  - [Memantine (Ebixa), glutaminergic modulator].
AB  - Alzheimer's disease (AD) is the most common etiology of dementia. Its incidence
      increases with age following an exponential trend of line between 60 and 90 years
      old. Anti-cholinesterasic drugs reduce modestly AD symptoms. However, they have
      no basic impact on the pathological evolution of the disease. Memantine offers
      another therapeutic approach in AD with a dissimilar mechanism of action,
      confronting neurotoxic effects of glutamate overload. It prevents the elevation
      of glutamate which destroys cholinergic neurons by inhibiting the N-methyl-D
      aspartate (NMDA) receptors. Its clinical efficiency has been demonstrated during
      28 weeks with 20 mg/day, in patients presenting moderate or severe AD and mild or
      moderately vascular dementia. Its use in association with anti-cholinesterasic
      (donepezil) revealed more interesting results with a significant improvement of
      cognitive functions and activities of daily live, compared to association placebo
      donepezil. We are waiting for results of further lenghter studies, including
      more, well-defined, patients.

PMID- 15157064
TI  - [External auditory meatus adenocarcinoma].
AB  - We report the case of a man presenting a deafness and a hemorrhagic ear discharge
      since one year. CT scanner and MRI reveal an invasive tumoral lesion of the
      external auditory meatus (EAM) expending into the posterior fossa. After surgery
      the diagnosis of high grade ceruminal gland adenocarcinoma is established whereas
      the malignancy was not obvious on earlier biopsy. Cancers arising in the EAM are
      uncommon and are essentially representating by squamous cell cancers and basal
      cell cancers. The precise diagnosis of a glandular tumor is a challenge for the
      pathologist because the limits between benign and malignant tumors are not
      obvious. Integration of clinical and radiological behavior and the histology of
      the tumor is necessary for a early diagnosis and a complete surgery.

PMID- 15157065
TI  - [The proper rules for publication].

PMID- 15157066
TI  - [Research in primary care].

PMID- 15157067
TI  - [The triumph of Toulouse-Lautrec].

PMID- 15157068
TI  - [Delivery of the highest award of Honorable Doctor to Mr. Philippe Bsquin,
      European Commissioner].

PMID- 15157069
TI  - Mutagenic mechanism of the A-T to G-C transition induced by 5-bromouracil: an ab
      Initio Study.
AB  - The tautomerisms of uracil, 5-bromouracil (BrU), G-U, G-BrU, A-U, and A-BrU have
      been studied theoretically in an effort to investigate the mutagenicity of BrU.
      The ab initio calculations have been performed using HF and B3LYP methods with
      various basis sets. The relative stability of all tautomers was established. The
      intermolecular interactions between U, BrU, U*, BrU* (asterisks denote enol
      forms), and water have been studied. It shows that the possibility of tautomerism
      from BrU to BrU* is much more likely than that from U to U*. Further research
      indicates that BrU* tends to pair with guanine more easily than U*. The proton
      transfer process has been investigated by potential energy surface (PES) scan and
      transition state analysis. The results show that the proton transfer between G-U*
      and G*-U is monodirectional barrier-free proton transfer (BFPT), which terminates
      the base mismatch induced by U*. On the other hand, the proton transfer between G
      BrU* and G*-BrU is bidirectional BFPT, which makes the base mismatch induced by
      BrU* sustained. On the basis of all of these calculated results, a new mutagenic
      mechanism for the A-T to G-C transition induced by 5-bromouracil is described in
      detail for the first time. It might give a new insight into the origin of the
      mutagenicity of the 5-Br derivative.

PMID- 15157070
TI  - Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from
      Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.
AB  - Di- and triketone inhibitors of (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) are
      both effective herbicides and therapeutics. The inhibitory activity is used to
      halt the production of lipophilic redox cofactors in plants and also in humans to
      prevent accumulation of toxic metabolic byproducts that arise from specific
      inborn defects of tyrosine catabolism. The three-dimensional structure of the
      Fe(II) form of HPPD from Streptomyces avermitilis in complex with the inhibitor 2
      [2-nitro-4-(triflouromethyl)benzoyl]-1,3-cyclohexanedione (NTBC) has been
      determined at a resolution of 2.5 A. NTBC coordinates to the active site metal
      ion, located at the bottom of a wide solvent-accessible cavity in the C-terminal
      domain of the protein. The iron is liganded in a predominantly five-coordinate,
      distorted square-pyramidal arrangement in which Glu349, His187, and His270 are
      protein-derived ligands and two other ligands are from the 5' and 7' oxygens of
      NTBC. There is a low-occupancy water molecule in the sixth coordination site in
      one of the protomers. The distance to His270 is unusually long at 2.5 A, and its
      orientation is somewhat distorted from ideal ligand geometry to within 2.8 A of
      the inhibitor nitro group. In contrast to the tetrameric quartenary structure
      observed for HPPD from other bacterial sources, the asymmetric unit is composed
      of two weakly associated protomers with a buried surface area of 1266 A(2) and a
      total of 12 hydrogen-bonding and no electrostatic interactions. The overall
      tertiary structure is similar to that of HPPD from Pseudomonas fluorescens (Serre
      et al., (1999) Structure 7, 977-988), although the position of the C-terminal
      alpha-helix is dramatically shifted. This C-terminal alpha-helix provides Phe364,
      which in combination with Phe336 sandwiches the phenyl ring of the bound NTBC; no
      other significant hydrogen-bonding or charge-pairing interactions are observed.
      Moreover, the structure reveals that, with the exception of Val189, NTBC makes
      contacts to only fully conserved amino acids. The combination of bidentate metal
      ion coordination and pi-stacked aromatic rings is suggestive of a binding mode
      for the substrate and/or a transition state, which may be the origin of the
      exceedingly high affinity these inhibitors have for HPPD.

PMID- 15157071
TI  - Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize
      one equivalent of lipoic acid.
AB  - Lipoyl synthase (LipA) catalyzes the formation of the lipoyl cofactor, which is
      employed by several multienzyme complexes for the oxidative decarboxylation of
      various alpha-keto acids, as well as the cleavage of glycine into CO(2) and
      NH(3), with concomitant transfer of its alpha-carbon to tetrahydrofolate,
      generating N(5),N(10)-methylenetetrahydrofolate. In each case, the lipoyl
      cofactor is tethered covalently in an amide linkage to a conserved lysine residue
      located on a designated lipoyl-bearing subunit of the complex. Genetic and
      biochemical studies suggest that lipoyl synthase is a member of a newly
      established class of metalloenzymes that use S-adenosyl-l-methionine (AdoMet) as
      a source of a 5'-deoxyadenosyl radical (5'-dA(*)), which is an obligate
      intermediate in each reaction. These enzymes contain iron-sulfur clusters, which
      provide an electron during the cleavage of AdoMet, forming l-methionine in
      addition to the primary radical. Recently, one substrate for lipoyl synthase has
      been shown to be the octanoylated derivative of the lipoyl-bearing subunit (E(2))
      of the pyruvate dehydrogenase complex [Zhao, S., Miller, J. R., Jian, Y.,
      Marletta, M. A., and Cronan, J. E., Jr. (2003) Chem. Biol. 10, 1293-1302].
      Herein, we show that the octanoylated derivative of the lipoyl-bearing subunit of
      the glycine cleavage system (H-protein) is also a substrate for LipA, providing
      further evidence that the cofactor is synthesized on its target protein.
      Moreover, we show that the 5'-dA(*) acts directly on the octanoyl substrate, as
      evidenced by deuterium transfer from [octanoyl-d(15)]H-protein to 5'
      deoxyadenosine. Last, our data indicate that 2 equiv of AdoMet are cleaved
      irreversibly in forming 1 equiv of [lipoyl]H-protein and are consistent with a
      model in which two LipA proteins are required to synthesize one lipoyl group.

PMID- 15157073
TI  - Effect of drastic sequence alteration and D-amino acid incorporation on the
      membrane binding behavior of lytic peptides.
AB  - The amphipathic alpha-helix is a common motif found in many cell lytic peptides
      including antimicrobial peptides. We have recently shown that significantly
      altering the amphipathic structure of a lytic peptide by reshuffling its sequence
      and/or replacing a few l-amino acids with their D-enantiomers did not
      significantly affect the antimicrobial activity of the peptides nor their ability
      to bind and permeate negatively charged (PE/PG) membranes. However, a pronounced
      effect was observed regarding their hemolytic activity and their ability to bind
      and permeate zwitterionic (PC/Cho) membranes. To shed light on these findings,
      here we used surface plasmon resonance (SPR) with mono- and bilayer membranes. We
      found that the L-amino acid (aa) peptides bound 10-25-fold stronger to PC/Cho
      bilayers compared with monolayers, whereas the diastereomers bound similarly to
      both membranes. A two-state reaction model analysis of the data indicated that
      this difference is due to the insertion of the L-aa peptides into the PC/Cho
      bilayers, whereas the diastereomers are surface-localized. In contrast, only an
      approximately 2-fold difference was found with negatively charged membranes.
      Changes in the amphipathicity markedly affected only the insertion of the L-aa
      peptides into PC/Cho bilayers. Furthermore, whereas the all-L-aa peptides bound
      similarly to the PC/Cho and PE/PG membranes, the diastereomers bound
      approximately 100-fold better to PE/PG compared with PC/Cho membranes, and
      selectivity was determined only in the first binding step. The effect of the
      peptides on the lipid order determined by using ATR-FTIR studies supported these
      findings. Besides shedding light on the mode of action of these peptides, the
      present study demonstrates SPR as a powerful tool to differentiate between non
      cell-selective compared with bacteria-selective peptides, based on differences in
      their membrane binding behavior.

PMID- 15157072
TI  - Identifying latent enzyme activities: substrate ambiguity within modern bacterial
      sugar kinases.
AB  - The ability of enzymes to catalyze the transformation of multiple, structurally
      related substrates could empower the natural evolution of new catalytic
      functions. The prevalence of such substrate ambiguity in modern catalysts,
      however, is largely unknown. To search for ambiguous sugar kinases, we generated
      a bacterium incapable of performing the first step of the glycolytic pathway, the
      phosphorylation of glucose. This organism cannot survive with glucose as its sole
      source of carbon. Within its genome, we find three DNA sequences that, when
      transcribed from a powerful extrachromosomal promoter, can complement the
      auxotrophy of the organism. These sequences contain the nanK, yajF, and ycfX
      genes. In vitro, the NanK, YajF, and YcfX proteins function as rudimentary
      glucokinases with ambiguous substrate specificites, displaying k(cat)/K(m) values
      for the phosphorylation of glucose that are 10(4)-fold lower than the k(cat)/K(m)
      value of endogenous bacterial glucokinase. Our findings suggest that modern
      genomes harbor a wealth of latent enzyme activities and that extant metabolic
      pathways are equivocal, in contrast to their usual depiction.

PMID- 15157074
TI  - Mechanism of the T286A-mutant alphaCaMKII interactions with Ca2+/calmodulin and
      ATP.
AB  - The role of adenosine 5'-triphosphate (ATP) in the activation mechanism of alpha
      Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII) was investigated
      using the T286A non-autophosphorylatable mutant of alphaCaMKII. Characterization
      of the T286A-alphaCaMKII mutant revealed k(cat) = 0.06 +/- 0.02 s(-1) for the
      T286A mutant, a 6 (+/- 2)-fold lower value compared to wild-type alphaCaMKII with
      100 microM smooth muscle myosin light chain (MLC) as substrate. MLC
      phosphorylation by the T286A mutant and wild-type alphaCaMKII was cooperative,
      with Hill coefficients 2.3 +/- 0.1 and 2.4 +/- 0.3, respectively. K(m) values for
      MLC were 96 +/- 28 microM with T286A-alphaCaMKII and 49 +/- 29 microM for wild
      type alphaCaMKII. Thus, while the activity of alphaCaMKII was sensitive to
      mutation of the Thr(286) residue to Ala, the mechanisms of the wild-type and
      T286A mutant enzyme appeared similar. K(d) for Ca(2+)/calmodulin was 2-fold
      reduced to 40 nM compared to that of wild-type alphaCaMKII (75 nM). ATP induced a
      9-fold stabilization of Ca(2+)/calmodulin binding to the T286A mutant enzyme.
      Fluorescence stopped-flow kinetic experiments revealed that two Ca(2+)/calmodulin
      enzyme complexes were formed, the first, unaffected by ATP, with association and
      dissociation rate constants of 2 x 10(7) M(-1) s(-1) and 5 s(-1), respectively,
      containing calmodulin in extended conformation. The second complex, in which
      calmodulin adopted a compact conformation, was formed with association rate
      constant 3 x 10(6) M(-1) s(-1) and dissociation at 0.15 s(-1) in the absence and
      0.015 s(-1) in the presence of ATP. These data show that ATP is involved in the
      activation mechanism by forming two classes of Ca(2+)/calmodulin.alphaCaMKII.ATP
      complex. It is likely that only one of the complexes is on the activation
      pathway.

PMID- 15157075
TI  - Aspartate transcarbamylase (ATCase) of Escherichia coli: a new crystalline R
      state bound to PALA, or to product analogues citrate and phosphate.
AB  - Structures of the R-state of Escherichia coli ATCase maintained with carbamyl
      phosphate and succinate, phosphonoacetamide and malonate, or N-phosphonacetyl-l
      aspartate (PALA) have previously been made in the space group P321, in which the
      two independent r (regulatory) and two independent c (catalytic) chains are
      repeated by crystallographic symmetry to yield the holoenzyme c(6)r(6),
      ((c(3))(2)(r(2))(3)). The exploration of a new crystalline R-state P2(1)2(1)2(1)
      was undertaken to examine the c(3).c(3) expansion of 11 A in the T-to-R
      transition, and to further test whether intermolecular contacts influence the
      binding of PALA. The results show that the expansion along the 3-fold axis is 10
      A, and that the binding modes of the six crystallographic independent PALA
      molecules are virtually identical to one another, and to modes described
      previously. As further test, the PALA, a bisubstrate analogue, was displaced by
      citrate and phosphate, where citrate is an analogue of product carbamylaspartate.
      The results support the conclusions about the binding of the three previously
      studied analogues, and further support, within about 0.5 A, the structure
      proposed for the transition state [Gouaux, J. E., Krause, K. L., and Lipscomb, W.
      N. (1987) Biochem. Biophys. Res. Commun. 142, 893-897; Jin, L., Stec, B.,
      Lipscomb, W. N., and Kantrowitz, E. R. (1999) Proteins: Struct., Funct., Genet.
      37, 729-742].

PMID- 15157076
TI  - Products in the T-state of aspartate transcarbamylase: crystal structure of the
      phosphate and N-carbamyl-L-aspartate ligated enzyme.
AB  - The structure of aspartate transcarbamylase of Escherichia coli ligated to
      products (phosphate and N-carbamyl-l-aspartate) has been determined at 2.37 A
      resolution (R-factor = 0.23, R(free) = 0.27). Results might indicate a product
      release mode, rather than close analogues to the transition state like those
      found in our earlier studies of other ligands (N-phosphonacetyl-L-aspartate,
      carbamyl phosphate plus malonate, phosphonoacetamide plus malonate, or citrate
      plus phosphate). Ordered product release, first carbamylaspartate (CLA) and then
      phosphate, might be facilitated by a 4 A movement of phosphate from the substrate
      analogue position to the product (phosphate) binding position, and by a somewhat
      similar release movement of the other product (CLA) relative to its analogue
      (citrate). This movement is consistent with earlier studies of binding of either
      pyrophosphate or phosphate alone [Honzatko, R. B., and Lipscomb, W. N. (1982) J.
      Mol. Biol. 160, 265-286].

PMID- 15157077
TI  - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase
      suprafamily: mechanistic evidence for a proton relay system in the active site of
      3-keto-L-gulonate 6-phosphate decarboxylase.
AB  - 3-Keto-L-gulonate 6-phosphate decarboxylase (KGPDC) and orotidine 5'
      monophosphate decarboxylase (OMPDC) are homologous enzymes that share the
      (beta/alpha)(8)-fold but catalyze mechanistically distinct reactions [Wise, E.,
      Yew, W. S., Babbitt, P. C., Gerlt, J. A., and Rayment, I. (2002) Biochemistry 41,
      3861-3869]. KGPDC catalyzes the Mg(2+)-dependent decarboxylation of 3-keto-L
      gulonate 6-phosphate, an intermediate in the catabolic pathway of L-ascorbate
      utilization by Escherichia coli K-12 [Yew, W. S., and Gerlt, J. A. (2002) J.
      Bacteriol. 184, 302-306]. OMPDC catalyzes a metal ion-independent reaction that
      likely proceeds without a vinyl anion intermediate [Appleby, T. C., Kinsland, C.,
      Begley, T., and Ealick, S. E. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 2005
      2010], although the mechanistic details are uncertain. An active site Lys located
      at the end of the third beta-strand in OMPDC has been proposed to be the general
      acid that delivers a solvent-derived proton to the UMP product; the active site
      of KGPDC contains a homologous Lys residue (Lys64). Herein, we report
      investigations of the KGPDC-catalyzed reaction that are consistent with a
      mechanism involving a Mg(2+)-stabilized cis-enediolate intermediate [Wise, E. L.,
      Yew, W. S., Gerlt, J. A., and Rayment, I. (2003) Biochemistry 42, 12133-12142]
      and implicate waters proximal to His136 and Arg139, both located at the end of
      the sixth beta-strand, as the general acids that deliver a solvent-derived proton
      to the intermediate to form the L-xylulose 5-phosphate product. On the basis of
      our mechanistic investigations, Lys64 stabilizes the cis-enediolate intermediate
      by forming hydrogen bonds to both O1 and O2 of the intermediate. Thus, although
      the active sites of OMPDC and KGPDC contain a conserved Lys at the end of the
      third beta-strand, their roles in catalysis are not conserved. Furthermore, a
      conserved Asp at the end of the third beta-strand in OMPDC participates in a
      hydrogen-bonded network that positions the acidic Lys residue; in the active site
      of KGPDC, the homologous Asp67 participates in stabilization of the enediolate
      intermediate and enforces a cis geometry. We conclude that the conserved active
      site residues perform different functions in the OMPDC- and KGPDC-catalyzed
      reactions, so the mechanisms of their reactions are completely distinct. This
      study further highlights the opportunistic nature of divergent evolution in
      conscripting the active site of a progenitor to catalyze a mechanistically
      distinct reaction.

PMID- 15157078
TI  - Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase
      suprafamily: crystallographic evidence for a proton relay system in the active
      site of 3-keto-L-gulonate 6-phosphate decarboxylase.
AB  - 3-Keto-L-gulonate 6-phosphate decarboxylase (KGPDC), a member of the orotidine
      monophosphate decarboxylase (OMPDC) suprafamily, catalyzes the Mg(2+)-dependent
      decarboxylation of 3-keto-L-gulonate 6-phosphate to L-xylulose 5-phosphate.
      Structural and biochemical evidence suggests that the KGPDC reaction proceeds via
      a Mg(2+)-stabilized 1,2-cis-enediolate intermediate. Protonation of the
      enediolate intermediate occurs in a nonstereospecific manner to form L-xylulose 5
      phosphate. Although the exact mechanism of proton delivery is not known, Glu112,
      His136, and Arg139 have been implicated in this process [Yew, W. S., Wise, E.,
      Rayment, I., and Gerlt, J. A. (2004) Biochemistry 43, 6427-6437]. Surprisingly,
      single amino acid substitutions of these positions do not substantially reduce
      catalytic activity but rather alter the stereochemical course of the reaction.
      Here, we report the X-ray crystal structures of four mutants, K64A, H136A, E112Q,
      and E112Q/H136A, each determined in the presence of L-threonohydroxamate 4
      phosphate, an analogue of the enediolate intermediate, to 1.7, 1.9, 1.8, and 1.9
      A resolution, respectively. These structures reveal that substitutions of Lys64,
      Glu112, and His136 cause changes in the positions of the intermediate analogue
      and two active site water molecules that were previously identified as possible
      proton donors. These changes correlate with the observed alterations in the
      reaction stereochemistry for these mutants, thereby supporting a reaction
      mechanism in which water molecules competitively shuttle protons from the side
      chains of His136 and Arg139 to alternate faces of the cis-enediolate
      intermediate. These studies further underscore the wide variation in the reaction
      mechanisms in the OMPDC suprafamily.

PMID- 15157080
TI  - Xylose isomerase in substrate and inhibitor michaelis states: atomic resolution
      studies of a metal-mediated hydride shift.
AB  - Xylose isomerase (E.C. 5.3.1.5) catalyzes the interconversion of aldose and
      ketose sugars and has an absolute requirement for two divalent cations at its
      active site to drive the hydride transfer rates of sugar isomerization. Evidence
      suggests some degree of metal movement at the second metal site, although how
      this movement may affect catalysis is unknown. The 0.95 A resolution structure of
      the xylitol-inhibited enzyme presented here suggests three alternative positions
      for the second metal ion, only one of which appears positioned in a catalytically
      competent manner. To complete the reaction, an active site hydroxyl species
      appears appropriately positioned for hydrogen transfer, as evidenced by precise
      bonding distances. Conversely, the 0.98 A resolution structure of the enzyme with
      glucose bound in the alpha-pyranose state only shows one of the metal ion
      conformations at the second metal ion binding site, suggesting that the linear
      form of the sugar is required to promote the second and third metal ion
      conformations. The two structures suggest a strong degree of conformational
      flexibility at the active site, which seems required for catalysis and may
      explain the poor rate of turnover for this enzyme. Further, the pyranose
      structure implies that His53 may act as the initial acid responsible for ring
      opening of the sugar to the aldose form, an observation that has been difficult
      to establish in previous studies. The glucose ring also appears to display
      significant segmented disorder in a manner suggestive of ring opening, perhaps
      lending insight into means of enzyme destabilization of the ground state to
      promote catalysis. On the basis of these results, we propose a modified version
      of the bridged bimetallic mechanism for hydride transfer in the case of
      Streptomyces olivochromogenes xylose isomerase.

PMID- 15157081
TI  - An electrostatically driven conformational transition is involved in the
      mechanisms of substrate binding and cooperativity in cytochrome P450eryF.
AB  - The effect of ionic strength (I) on substrate-induced spin transitions and
      cooperativity in cytochrome P450eryF was studied. At a saturating concentration
      of 1-pyrenebutanol (1-PB) increasing ionic strength in the 0.06-1.2 M range
      promotes the formation of the high-spin state of P450, which fraction increases
      from 26% at 0.06 M to 75% at 1.2 M. This effect was associated with a
      considerable decrease in cooperativity as revealed in the 1-PB-induced spin
      shift. While P450eryF exhibits distinct positive cooperativity (S(50) = 8.3
      microM, n = 2.4) with this substrate at low ionic strength (I = 0.06 M), n
      decreases to 1.2 (S(50) = 3.2 microM) at I = 0.66 M. Increasing ionic strength
      also increases the distance between the first (effector) molecule of 1-PB and the
      heme, as detected by the changes in the efficiency of FRET from 1-PB to the heme.
      The modification of Cys(154) with 7-(diethylamino)-3-(4'-maleimidylphenyl)-4
      methylcoumarin (CPM) largely suppresses these effects of ionic strength and
      causes a prominent decrease in the cooperativity. The same effect was observed
      when Cys(154) was substituted with isoleucine. Importantly, Cys(154) is located
      at the C-terminal end of helix E and is surrounded by salt bridges formed by
      arginine, glutamate, and aspartate residues located in helices D, E, F, and G.
      Our results suggest that the binding of the first substrate molecule causes an
      important conformational transition in the P450eryF that facilitates the
      substrate-induced spin shift. This transition is apparently accompanied by
      dissociation or rearrangement of several salt bridges in the proximity of
      Cys(154) and modulates accessibility and hydration of the heme pocket.

PMID- 15157082
TI  - Assembly of an active group II intron-maturase complex by protein dimerization.
AB  - Group II intron-encoded proteins promote both splicing and mobility of the intron
      RNA through formation of a specific RNA-protein complex. The Lactococcus lactis
      L1.LtrB intron encodes a maturase, LtrA, with reverse transcriptase homology and
      specific binding affinity for two domains of the intron RNA. The catalytically
      active ribonucleoprotein (RNP) has splicing, endonuclease, and reverse
      transcriptase activity, enabling efficient insertion of the intron sequence by a
      retro-homing mechanism. To determine the composition and assembly mechanism of
      the RNP complex, purified LtrA protein was analyzed for its ability to recognize
      a series of intron-derived RNAs. Equilibrium dissociation measurements show that
      LtrA recognizes two intronic domains, DI and DIV. However, distinct electrostatic
      requirements for binding imply different modes of molecular recognition in each
      case. Stoichiometric binding experiments show that the functional RNP complex
      consists of a dimeric protein species bound to a single intron RNA. Significant
      differences between the measured equilibrium dissociation constants and
      kinetically derived values suggest that conformational changes accompany assembly
      of the intron-maturase complex, and results of limited proteolysis and
      fluorescence spectroscopy experiments suggest that significant RNA-dependent
      structural changes within the maturase occur upon association with the intron.
      These results support a mutually induced fit model in which RNA-dependent
      conformational changes within LtrA enable stable association of the protein dimer
      with two independent intron domains to form a functional RNP.

PMID- 15157083
TI  - Thermodynamic basis of electron transfer in dihydroorotate dehydrogenase B from
      Lactococcus lactis: analysis by potentiometry, EPR spectroscopy, and ENDOR
      spectroscopy.
AB  - Dihydroorotate dehydrogenase B (DHODB) is a complex iron-sulfur flavoprotein that
      catalyzes the conversion of dihydroorotate to orotate and the reduction of
      NAD(+). The enzyme is a dimer of heterodimers containing an FMN, an FAD, and a
      2Fe-2S center. UV-visible, EPR, and ENDOR spectroscopies have been used to
      determine the reduction potentials of the flavins and the 2Fe-2S center and to
      characterize radicals and their interactions. Reductive titration using
      dithionite indicates a five-electron capacity for DHODB. The midpoint reduction
      potential of the 2Fe-2S center (-212 +/- 3 mV) was determined from analysis of
      absorption data at 540 nm, where absorption contributions from the two flavins
      are small. The midpoint reduction potentials of the oxidized/semiquinone (E(1))
      and semiquinone/hydroquinone (E(2)) couples for the FMN (E(1) = -301 +/- 6 mV;
      E(2) = -252 +/- 8 mV) and FAD (E(1) = -312 +/- 6 mV; E(2) = -297 +/- 5 mV) were
      determined from analysis of spectral changes at 630 nm. Corresponding values for
      the midpoint reduction potentials for FMN (E(1) = -298 +/- 4 mV; E(2) = -259 +/-
      5 mV) in the isolated catalytic subunit (subunit D, which lacks the 2Fe-2S center
      and FAD) are consistent with the values determined for the FMN couples in DHODB.
      During reductive titration of DHODB, small amounts of the neutral blue
      semiquinone are observed at approximately 630 nm, consistent with the measured
      midpoint reduction potentials of the flavins. An ENDOR spectrum of substrate
      reduced DHODB identifies hyperfine couplings to proton nuclei similar to those
      recorded for the blue semiquinone of free flavins in aqueous solution, thus
      confirming the presence of this species in DHODB. Spectral features observed
      during EPR spectroscopy of dithionite-reduced DHODB are consistent with the
      midpoint reduction potentials determined using UV-visible spectroscopy and
      further identify an unusual EPR signal with very small rhombic anisotropy and g
      values of 2.02, 1.99, and 1.96. This unusual signal is assigned to the formation
      of a spin interacting state between the FMN semiquinone species and the reduced
      2Fe-2S center. Reduction of DHODB using an excess of NADH or dihydroorotate
      produces EPR spectra that are distinct from those produced by dithionite. From
      potentiometric studies, the reduction of the 2Fe-2S center and the reduction of
      the FMN occur concomitantly. The study provides a detailed thermodynamic
      framework for electron transfer in this complex iron-sulfur flavoprotein.

PMID- 15157079
TI  - Crystal structure of Escherichia coli cytidine triphosphate synthetase, a
      nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion
      protein and homologue of anticancer and antiparasitic drug targets.
AB  - Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and glutamine, and
      regulate intracellular CTP levels through interactions with the four
      ribonucleotide triphosphates. We solved the 2.3-A resolution crystal structure of
      Escherichia coli CTPS using Hg-MAD phasing. The structure reveals a nearly
      symmetric 222 tetramer, in which each bifunctional monomer contains a
      dethiobiotin synthetase-like amidoligase N-terminal domain and a Type 1 glutamine
      amidotransferase C-terminal domain. For each amidoligase active site, essential
      ATP- and UTP-binding surfaces are contributed by three monomers, suggesting that
      activity requires tetramer formation, and that a nucleotide-dependent dimer
      tetramer equilibrium contributes to the observed positive cooperativity. A gated
      channel that spans 25 A between the glutamine hydrolysis and amidoligase active
      sites provides a path for ammonia diffusion. The channel is accessible to solvent
      at the base of a cleft adjoining the glutamine hydrolysis active site, providing
      an entry point for exogenous ammonia. Guanine nucleotide binding sites of
      structurally related GTPases superimpose on this cleft, providing insights into
      allosteric regulation by GTP. Mutations that confer nucleoside drug resistance
      and release CTP inhibition map to a pocket that neighbors the UTP-binding site
      and can accommodate a pyrimidine ring. Its location suggests that competitive
      feedback inhibition is affected via a distinct product/drug binding site that
      overlaps the substrate triphosphate binding site. Overall, the E. coli structure
      provides a framework for homology modeling of other CTPSs and structure-based
      design of anti-CTPS therapeutics.

PMID- 15157084
TI  - The factors governing the thermal stability of frataxin orthologues: how to
      increase a protein's stability.
AB  - Understanding the factors governing the thermal stability of proteins and
      correlating them to the sequence and structure is a complex and multiple problem
      that can nevertheless provide important information on the molecular forces
      involved in protein folding. Here, we have carried out a comparative genomic
      study to analyze the effects that different intrinsic and environmental factors
      have on the thermal stability of frataxins, a family of small mitochondrial iron
      binding proteins found in organisms ranging from bacteria to humans. Low
      expression of frataxin in humans causes Friedreich's ataxia, an autosomal
      recessive neurodegenerative disease. The human, yeast, and bacterial orthologues
      were selected as representatives of different evolutionary steps. Although
      sharing high sequence homology and the same three-dimensional fold, the three
      proteins have a large variability in their thermal stabilities. Whereas bacterial
      and human frataxins are thermally stable, well-behaved proteins, under the same
      conditions yeast frataxin exists in solution as an unstable species with
      apprechable tracts in a conformational exchange. By designing suitable mutants,
      we show and justify structurally that the length of the C-terminus is an
      important intrinsic factor that directly correlates with the thermal stabilities
      of the three proteins. Thermal stability is also gained by the addition of
      Fe(2+). This effect, however, is not uniform for the three orthologues nor highly
      specific for iron: a similar albeit weaker stabilization is observed with other
      mono- and divalent cations. We discuss the implications that our findings have
      for the role of frataxins as iron-binding proteins.

PMID- 15157085
TI  - Disulfide bonding arrangements in active forms of the somatomedin B domain of
      human vitronectin.
AB  - The N-terminal cysteine-rich somatomedin B (SMB) domain (residues 1-44) of the
      human glycoprotein vitronectin contains the high-affinity binding sites for
      plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR). We
      previously showed that the eight cysteine residues of recombinant SMB (rSMB) are
      organized into four disulfide bonds in a linear uncrossed pattern (Cys(5)-Cys(9),
      Cys(19)-Cys(21), Cys(25)-Cys(31), and Cys(32)-Cys(39)). In the present study, we
      use an alternative method to show that this disulfide bond arrangement remains a
      major preferred one in solution, and we determine the solution structure of the
      domain using NMR analysis. The solution structure shows that the four disulfide
      bonds are tightly packed in the center of the domain, replacing the traditional
      hydrophobic core expected for a globular protein. The few noncysteine hydrophobic
      side chains form a cluster on the outside of the domain, providing a distinctive
      binding surface for the physiological partners PAI-1 and uPAR. The hydrophobic
      surface consists mainly of side chains from the loop formed by the Cys(25)
      Cys(31) disulfide bond, and is surrounded by conserved acidic and basic side
      chains, which are likely to contribute to the specificity of the intermolecular
      interactions of this domain. Interestingly, the overall fold of the molecule is
      compatible with several arrangements of the disulfide bonds. A number of
      different disulfide bond arrangements were able to satisfy the NMR restraints,
      and an extensive series of conformational energy calculations performed in
      explicit solvent confirmed that several disulfide bond arrangements have
      comparable stabilization energies. An experimental demonstration of the presence
      of alternative disulfide conformations in active rSMB is provided by the behavior
      of a mutant in which Asn(14) is replaced by Met. This mutant has the same PAI-1
      binding activity as rVN1-51, but its fragmentation pattern following cyanogen
      bromide treatment is incompatible with the linear uncrossed disulfide
      arrangement. These results suggest that active forms of the SMB domain may have a
      number of allowed disulfide bond arrangements as long as the Cys(25)-Cys(31)
      disulfide bond is preserved.

PMID- 15157086
TI  - Substrate profiling of deubiquitin hydrolases with a positional scanning library
      and mass spectrometry.
AB  - Deconjugation of ubiquitin from cellular proteins is catalyzed by the deubiquitin
      hydrolase (DUB) family of enzymes and is an important component of the ubiquitin
      regulatory system affecting cellular function beyond simple maintenance of
      monomeric pools of ubiquitin. Specific deconjugation of ubiquitinated substrates
      has been described, but substrate recognition is poorly understood. To determine
      whether specificity may be conferred by recognition of a primary cognate
      sequence, the substrate preferences of two DUBs, UCH-L3 and isopeptidase T
      (IsoT), were profiled using a positional scanning branched peptide library. The
      sequence of the library was based on K48-branched diubiquitin,
      RLXXXXK(GGRLRLVL)QLEDGR, where X denotes a diversified position in the library
      (P1' '-P4' ' numbered from K48). Hydrolysis of the branched peptide was
      indicative of DUB activity and was detected and quantified by mass spectrometry.
      IsoT was active toward the library but demonstrated little preference for the
      diversified positions. In contrast, UCH-L3 exhibited minor amino acid preferences
      at P2' ' and P4' ' and a 10-fold preference for the basic residues Arg and Lys at
      P3' '. Kinetic analysis of substrates with optimized and suboptimized sequences
      (as defined by the library profile) confirmed the preference at P3' '. Substrate
      inhibition of UCH-L3 but not IsoT was noted for the optimized sequence at
      concentrations greater than 5 microM and with an IC(50) of 12.2 microM; the
      inhibition was determined to be competition with Ub-AMC (ubiquitin C-terminal 7
      amido-4-methylcoumarin).

PMID- 15157087
TI  - Orientating peptide residues and increasing the distance between pockets to
      enable fitting into MHC-TCR complex determine protection against malaria.
AB  - The erythrocyte binding antigen EBA-175 is a 175-kDa Plasmodium falciparum
      protein, which has been shown to be involved in the process of invasion of
      erythrocytes. It has been found that conserved peptide 1818 belonging to this
      protein has high red blood cell binding capacity and plays an important role in
      the invasion process. This peptide is neither immunogenic nor protective. Peptide
      1818 analogues had some of their previously recognized critical red blood cell
      binding residues substituted for amino acids having similar volume or mass but
      different polarity to make them fit into HLA-DRbeta(1)*1101 molecules; these 1818
      peptide analogues were then synthesized and inoculated into Aotus nancymaae
      monkeys, generating different immunogenic and/or protective immune responses.
      Short structures such as 3(10)-helix, classical, or distorted type-III beta-turns
      were found in the immunogenic and protective peptides once the secondary
      structure had been analyzed by NMR and its structure correlated with its
      immunological properties. These data suggest that peptide flexibility may lead to
      better fitting into immune system molecules, therefore making them excellent
      candidates for consideration as components of a subunit-based, multicomponent
      synthetic antimalarial vaccine.

PMID- 15157088
TI  - Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to
      EF-hand proteins.
AB  - EF-hands are Ca(2+) binding motifs that are widely distributed throughout the
      entire living organism kingdom. At present, relatively little is known at a
      quantum mechanical level about the mechanisms that allow Ca(2+) to be recognized
      specifically by EF-hands and to induce a conformational switch from a compact
      ("closed") conformation to an "open" state that exposes a large patch of
      hydrophobic residues. Here, we present a study of NMR (15)N chemical shifts based
      on ab initio quantum mechanical calculations carried out on a minimalist model
      system linking both Ca(2+) binding sites across the beta-sheet of an EF-hand
      domain. Calculated and experimentally determined chemical shift changes are
      correlated with structural changes induced upon metal binding. The effect of
      Ca(2+) binding on these (15)N shifts can be dissected into two main
      contributions: one from pi-polarization of beta-sheet amide groups and the other
      from rotation of an isoleucine side chain. By correlating this description with
      experimental evidence, different polarization states for the beta-sheet amide
      groups were identified and linked to the overall conformation of different EF
      hand domains. When all four beta-sheet amide groups are polarized, the ab initio
      calculations in our model indicate a cooperative stabilization effect due to the
      establishment of a circular network of donor-acceptor interactions connecting the
      two Ca(2+) ions across the beta-sheet. The emerging hypothesis from our analysis
      is that this cooperative network of interactions is essential for stabilizing the
      "open" conformation of an EF-hand domain.

PMID- 15157089
TI  - Tetrahedral intermediates in thiamin diphosphate-dependent decarboxylations exist
      as a 1',4'-imino tautomeric form of the coenzyme, unlike the michaelis complex or
      the free coenzyme.
AB  - Two circular dichroism signals observed on thiamin diphosphate (ThDP)-dependent
      enzymes, a positive band in the 300-305 nm range and a negative one in the 320
      330 nm range, were investigated on yeast pyruvate decarboxylase (YPDC) and on the
      E1 subunit of the Escherichia coli pyruvate dehydrogenase complex (PDHc-E1).
      Addition of the tetrahedral ThDP-acetaldehyde adduct, 2-alpha-hydroxyethylThDP,
      to PDHc-E1 generates the positive band at 300 nm, consistent with the formation
      of the 1',4'-iminopyrimidine tautomer, as also demonstrated for
      phosphonolactylthiamin diphosphate, a stable analogue of the tetrahedral ThDP
      pyruvate adduct 2-alpha-lactylThDP (Jordan, F. et al. (2003) J. Am. Chem. Soc.
      125, 12732-12738). Therefore, we suggest that all tetrahedral ThDP-bound covalent
      complexes will also prefer this tautomer, and that the 4'-aminopyrimidine of ThDP
      participates in multiple steps of acid-base catalysis on ThDP enzymes. Studies
      with YPDC and PDHc-E1, and their active center variants, in conjunction with
      chemical models, enabled assignment of the negative band at 330 nm to a charge
      transfer transition between the 4'-aminopyrimidine tautomer (presumed electron
      donor) and the thiazolium ring (presumed electron acceptor) of ThDP, with no
      significant contributions from any amino acid side chain of the proteins.
      However, in both YPDC and PDHc-E1, the presence of substrate or substrate
      surrogate was required to enable detection, suggesting that the band at 320-330
      nm be used as a reporter for the Michaelis complex, involving the amino tautomer,
      on both enzymes. As the positive band near 300 nm reports on the 1',4'-imino
      tautomer of ThDP, methods are now available for kinetic monitoring of both
      tautomeric forms.

PMID- 15157090
TI  - Limited proteolysis of human growth hormone at low pH: isolation,
      characterization, and complementation of the two biologically relevant fragments
      1-44 and 45-191.
AB  - The limited proteolysis approach was used to analyze the conformational features
      of human growth hormone (hGH) under acidic solvent conditions (A-state). Pepsin
      was used as the proteolytic probe because of its poor substrate specificity and
      its activity at low pH. Limited proteolysis of hGH in its A-state results in a
      selective cleavage of the Phe44-Leu45 peptide bond, leading to the production of
      fragments 1-44 and 45-191. The two fragments were isolated in homogeneous form
      for studying their conformational properties by means of spectroscopic methods.
      Fragment 1-44 was shown to retain little secondary and tertiary structure at
      neutral pH, while fragment 45-191 independently folds into a highly helical
      secondary structure. In particular, we have shown that the two peptic fragments
      are able to associate into a stable and native-like hGH complex 1-44/45-191. Our
      proteolysis data indicate that in acid solution hGH adopts a partly folded state
      characterized by a local unfolding of the first minihelix (residues 38-47)
      encompassing the Phe44-Leu45 peptide bond. Of interest, hGH has both insulin-like
      and diabetogenic effects. Two fragments of hGH occur in vivo and exert these two
      opposite activities, namely, fragment 1-43 showing an insulin-potentiating effect
      and fragment 44-191 showing a diabetogenic activity. The results of this study
      suggest that the conformational changes of hGH induced by an acidic pH promote
      the generation of the two physiologically relevant fragments by proteolytic
      processing of the hormone. Although pepsin cannot be the enzyme responsible for
      the in vivo processing of the hormone, we propose that limited proteolysis of hGH
      at low pH is physiologically relevant, since the hormone is exposed to an acidic
      environment in the cell. This study reports for the first time the analysis of
      the conformational features of the two individual functional domains of hGH and
      of their complex.

PMID- 15157091
TI  - The activity of selected RB69 DNA polymerase mutants can be restored by manganese
      ions: the existence of alternative metal ion ligands used during the
      polymerization cycle.
AB  - Site specific mutants in the pol active center of RB69 DNA polymerase have been
      produced and studied using rapid chemical-quench techniques. Pre-steady-state
      kinetic analysis carried out with Mg(2+) and Mn(2+) has enabled us to divide the
      mutants into two groups. One group had greatly reduced k(pols) values in the
      presence of Mg(2+) but responded to Mn(2+) which restored the k(pol) values for
      the nucleotidyl transfer reaction to near wild-type levels. The other group of
      mutants also had lower k(pol) values, relative to that of the wild-type
      polymerase, but could not be rescued by Mn(2+). The behavior of these mutants was
      interpreted in terms of the crystal structures of the available RB69 pol
      complexes. Our results on the metal ion dependence of the D621A and E686A
      mutants, together with knowledge of the position of their side chains in two
      different RB69 pol conformations, suggest that these acidic residues serve as
      alternative ligands for the metal ions destined to occupy the A and B catalytic
      sites. We infer that this occurs prior to the conformational change that produces
      the ternary RB69 pol complex in which the A and B metal ions are ligated by D623
      and D411 as the enzyme is poised for phosphoryl transfer.

PMID- 15157092
TI  - Key elements for protein foldability revealed by a combinatorial approach among
      similarly folded but distantly related proteins.
AB  - We have determined the key regions for protein foldability by creating multiple
      crossover libraries from two proteins that share similar fold but have low
      sequence identity and differ significantly in stability. One protein is the
      propeptide of a serine protease, subtilisin BPN', and the other is Pleurotus
      ostreatus proteinase A inhibitor 1 (POIA1). The propeptide has a compact
      structure when complexed with subtilisin but is unstructured when isolated,
      whereas POIA1 takes a stable structure. We selected four of the conserved amino
      acid residues for the boundaries of crossover sites and utilized these residues
      to make same cohesive-ends to assemble synthetic DNA fragments. Each segment has
      one or two secondary structure units, and the interchange of these structural
      elements produces 32 (= 2(5)) combinations, including the propeptide and POIA1.
      The stability of these mutants was first screened by formation of turbid zones on
      skim milk plates containing subtilisin BPN'. It was shown that six variants were
      foldable and structural units necessary for folding were identified. Further
      fragmentation and recombination of these mutants (the "multisection" method)
      revealed that two interactions between secondary structures are important; one is
      interaction between the loop-alpha1 and beta2-turn-beta3, and the other is
      hydrophobic interaction between the adjoining beta1 and beta4 strands. We were
      also able to specify the significant amino acid combinations for tolerance to
      proteolysis. These combinatorial methods not only elucidate how domains can be
      interchanged to make the whole protein foldable but also extract essential
      regions for the function, which is correlated with the instability of the
      molecule.

PMID- 15157093
TI  - Characterization of the complex of a trifluoromethyl-substituted shikimate-based
      bisubstrate inhibitor and 5-enolpyruvylshikimate-3-phosphate synthase by REDOR
      NMR.
AB  - A combination of (15)N[(19)F], (31)P[(15)N], and (31)P[(19)F] rotational-echo
      double-resonance NMR has been used to characterize the conformation of a bound
      trifluoromethylketal, shikimate-based bisubstrate inhibitor of 5
      enolpyruvylshikimate-3-phosphate synthase. The solid-state NMR experiments were
      performed on the complex formed in solution and then lyophilized at low
      temperatures in the presence of stabilizing lyoprotectants. The results of these
      experiments indicate that none of the side chains of the six arginines that
      surround the active site forms a compact salt bridge with the phosphate groups of
      the bound inhibitor.

PMID- 15157094
TI  - Identification of functionally important residues in the pyridoxal-5'-phosphate
      dependent catalytic antibody 15A9.
AB  - Antibody 15A9 is unique in its ability to catalyze the transamination reaction of
      hydrophobic D-amino acids with pyridoxal-5'-phosphate (PLP). Both previous
      chemical modification studies and a three dimensional (3-D) homology model
      indicated the presence of functionally important tyrosine residues in the antigen
      binding cavity of antibody 15A9. To gain further insight into the hapten, ligand
      binding, and catalytic mechanism of 15A9, all tyrosine residues in the
      complementarity-determining regions (CDRs) and the single arginine residue in
      CDR3 of the light chain were subject to an alanine scan. Substitution of
      Tyr(H33), Tyr(L94), or Arg(L91) abolished the catalytic activity and reduced the
      affinity for PLP and N(a)-(5'-phosphopyridoxyl)-amino acids, which are close
      analogues of covalent PLP-substrate adducts. The Tyr(H100b)Ala mutant possessed
      no detectable catalytic activity, while its affinity for each ligand was
      essentially the same as that of the wild-type antibody. The binding affinity for
      the hapten was drastically reduced by a Tyr(L32)Ala mutation, suggesting that the
      hydroxyphenyl group of Tyr(L32) participates in the binding of the extended side
      chain of the hapten. The other Tyr --> Ala substitutions affected both binding
      and catalytic activity only to a minor degree. On the basis of the information
      obtained from the mutagenesis study, we docked N(alpha)-(5'-phosphopyridoxyl)-D
      alanine into the antigen-binding site. According to this model, Arg(L91) binds
      the alpha-carboxylate group of the amino acid substrate and Tyr(H100b) plays an
      essential role in the catalytic mechanism of antibody 15A9 by facilitating the
      Calpha/C4' prototropic shift. In addition, the catalytic apparatus of antibody
      15A9 revealed several mechanistic features that overlap with those of PLP
      dependent enzymes.

PMID- 15157095
TI  - Crystal structures of RIalpha subunit of cyclic adenosine 5'-monophosphate (cAMP)
      dependent protein kinase complexed with (Rp)-adenosine 3',5'-cyclic
      monophosphothioate and (Sp)-adenosine 3',5'-cyclic monophosphothioate, the
      phosphothioate analogues of cAMP.
AB  - Cyclic adenosine 5'-monophosphate (cAMP) is an ancient signaling molecule, and in
      vertebrates, a primary target for cAMP is cAMP-dependent protein kinase (PKA).
      (R(p))-adenosine 3',5'-cyclic monophosphothioate ((R(p))-cAMPS) and its analogues
      are the only known competitive inhibitors and antagonists for cAMP activation of
      PKA, while (S(p))-adenosine 3',5'-cyclic monophosphothioate ((S(p))-cAMPS)
      functions as an agonist. The crystal structures of a Delta(1-91) deletion mutant
      of the RIalpha regulatory subunit of PKA bound to (R(p))-cAMPS and (S(p))-cAMPS
      were determined at 2.4 and 2.3 A resolution, respectively. While the structures
      are similar to each other and to the crystal structure of RIalpha bound to cAMP,
      differences in the dynamical properties of the protein when (R(p))-cAMPS is bound
      are apparent. The structures highlight the critical importance of the exocyclic
      oxygen's interaction with the invariant arginine in the phosphate binding
      cassette (PBC) and the importance of this interaction for the dynamical
      properties of the interactions that radiate out from the PBC. The conformations
      of the phosphate binding cassettes containing two invariant arginine residues
      (Arg209 on domain A, and Arg333 on domain B) are somewhat different due to the
      sulfur interacting with this arginine. Furthermore, the B-site ligand together
      with the entire domain B show significant differences in their overall dynamic
      properties in the crystal structure of Delta(1-91) RIalpha complexed with (R(p))
      cAMPS phosphothioate analogue ((R(p))-RIalpha) compared to the cAMP- and (S(p))
      cAMPS-bound type I and II regulatory subunits, based on the temperature factors.
      In all structures, two structural solvent molecules exist within the A-site
      ligand binding pocket; both mediate water-bridged interactions between the ligand
      and the protein. No structured waters are in the B-site pocket. Owing to the
      higher resolution data, the N-terminal segment (109-117) of the RIalpha subunit
      can also be traced. This strand forms an intermolecular antiparallel beta-sheet
      with the same strand in an adjacent molecule and implies that the RIalpha subunit
      can form a weak homodimer even in the absence of its dimerization domain.

PMID- 15157096
TI  - The crystal structure of Sulfolobus solfataricus elongation factor 1alpha in
      complex with magnesium and GDP.
AB  - Recent studies have shown that elongation factors extracted from archaea/eukarya
      and from eubacteria exhibit different structural and functional properties. Along
      this line, it has been demonstrated that, in contrast to EF-Tu, Sulfolobus
      solfataricus EF-1alpha in complex with GDP (SsEF-1alpha.GDP) does not bind
      Mg(2+), when the ion is present in the crystallization medium at moderate
      concentration (5 mM). To further investigate the role that magnesium plays in the
      exchange process of EF-1alpha and to check the ability of SsEF-1alpha.GDP to bind
      the ion, we have determined the crystal structure of SsEF-1alpha.GDP in the
      presence of a nonphysiological concentration (100 mM) of Mg(2+). The analysis of
      the coordination of Mg(2+) unveils the structural bases for the marginal role
      played by the ion in the nucleotide exchange process. Furthermore, nucleotide
      exchange experiments carried out on a truncated form of SsEF-1alpha, consisting
      only of the nucleotide binding domain, demonstrate that the low affinity of SsEF
      1alpha.GDP for Mg(2+) is due to the local architecture of the active site and
      does not depend on the presence of the other two domains. Finally, considering
      the available structures of EF-1alpha, a detailed mechanism for the nucleotide
      exchange process has been traced. Notably, this mechanism involves residues such
      as His14, Arg95, Gln131, and Glu134, which are strictly conserved in all archaea
      and eukarya EF-1alpha sequences hitherto reported.

PMID- 15157098
TI  - Antimitotic antifungal compound benomyl inhibits brain microtubule polymerization
      and dynamics and cancer cell proliferation at mitosis, by binding to a novel site
      in tubulin.
AB  - The antifungal agent benomyl [methyl-1-(butylcarbamoyl)-2-benzimidazolecarbamate]
      is used throughout the world against a wide range of agricultural fungal
      diseases. In this paper, we investigated the interaction of benomyl with
      mammalian brain tubulin and microtubules. Using the hydrophobic fluorescent probe
      1-anilinonaphthalene-8-sulfonic acid, benomyl was found to bind to brain tubulin
      with a dissociation constant of 11.9 +/- 1.2 microM. Further, benomyl bound to at
      a novel site, distinct from the well-characterized colchicine and vinblastine
      binding sites. Benomyl altered the far-UV circular dichroism spectrum of tubulin
      and reduced the accessibility of its cysteine residues to modification by 5,5'
      dithiobis-2-nitrobenzoic acid, indicating that benomyl binding to tubulin induces
      a conformational change in the tubulin. Benomyl inhibited the polymerization of
      brain tubulin into microtubules, with 50% inhibition occurring at a concentration
      of 70-75 microM. Furthermore, it strongly suppressed the dynamic instability
      behavior of individual brain microtubules in vitro as determined by video
      microscopy. It reduced the growing and shortening rates of the microtubules but
      did not alter the catastrophe or rescue frequencies. The unexpected potency of
      benomyl against mammalian microtubule polymerization and dynamics prompted us to
      investigate the effects of benomyl on HeLa cell proliferation and mitosis.
      Benomyl inhibited proliferation of the cells with an IC(50) of 5 microM, and it
      blocked mitotic spindle function by perturbing microtubule and chromosome
      organization. The greater than expected actions of benomyl on mammalian
      microtubules and mitosis together with its relatively low toxicity suggest that
      it might be useful as an adjuvant in cancer chemotherapy.

PMID- 15157097
TI  - Structural analysis of botulinum neurotoxin type E catalytic domain and its
      mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate in the
      catalytic pathway.
AB  - The seven serotypes of botulinum neurotoxins (A-G) produced by Clostridium
      botulinum share significant sequence homology and structural similarity. The
      functions of their individual domains and the modes of action are also similar.
      However, the substrate specificity and the peptide bond cleavage selectivity of
      their catalytic domains are different. The reason for this unique specificity of
      botulinum neurotoxins is still baffling. If an inhibitor leading to a therapeutic
      drug common to all serotypes is to be developed, it is essential to understand
      the differences in their three-dimensional structures that empower them with this
      unique characteristic. Accordingly, high-resolution structures of all serotypes
      are required, and toward achieving this goal the crystal structure of the
      catalytic domain of C. botulinum neurotoxin type E has been determined to 2.1 A
      resolution. The crystal structure of the inactive mutant Glu212-->Gln of this
      protein has also been determined. While the overall conformation is unaltered in
      the active site, the position of the nucleophilic water changes in the mutant,
      thereby causing it to lose its ability to activate the catalytic reaction. The
      structure explains the importance of the nucleophilic water and the charge on
      Glu212. The structural differences responsible for the loss of activity of the
      mutant provide a common model for the catalytic pathway of Clostridium
      neurotoxins since Glu212 is conserved and has a similar role in all serotypes.
      This or a more nonconservative mutant (e.g., Glu212-->Ala) could provide a novel,
      genetically modified protein vaccine for botulinum.

PMID- 15157099
TI  - Iodo-alpha-conotoxin MI selectively binds the alpha/delta subunit interface of
      muscle nicotinic acetylcholine receptors.
AB  - The embryonic mouse muscle nicotinic acetylcholine receptor (nAChR) is a ligand
      gated ion channel formed by alpha1, beta1, delta, and gamma subunits. The
      receptor contains two ligand binding sites at alpha/delta and alpha/gamma subunit
      interfaces. [(3)H]Curare preferentially binds the alpha/gamma interface. We
      describe the synthesis and properties of a high-affinity iodinated ligand that
      selectively binds the alpha/delta interface. An analogue of alpha-conotoxin MI
      was synthesized with an iodine attached to Tyr-12 (iodo-alpha-MI). The analogue
      potently blocks the fetal mouse muscle subtype of nAChR expressed in Xenopus
      oocytes. It failed, however, to block alpha3beta4, alpha4beta2, or alpha7 nAChRs.
      Iodo-alpha-MI potently blocks the alpha1beta1delta but not the alpha1beta1gamma
      subunit combination expressed in Xenopus oocytes indicating selectivity for the
      alpha/delta subunit interface. Alpha-conotoxin MI was subsequently
      radioiodinated, and its properties were further evaluated. Saturation experiments
      indicate that radioiodinated alpha-conotoxin MI binds to TE671 cell homogenates
      with a Hill slope of 0.95 +/- 0.0094. Kinetic studies indicate that the binding
      of [(125)I]alpha-conotoxin MI is reversible (k(off) = 0.084 +/- 0.0045 min(-1));
      k(on) is 8.5 x 10(7) min(-1) M(-1). The calculated k(d) is 0.98 nM. This potency
      is approximately 20-fold higher than the unmodified alpha-MI peptide. Unlike
      [(125)I]alpha-bungarotoxin, [(125)I]alpha-conotoxin MI binding to TE671 cell
      homogenates is fully displaceable by the small molecule antagonist d
      tubocurarine.

PMID- 15157100
TI  - NMR characterization of three-disulfide variants of lysozyme, C64A/C80A,
      C76A/C94A, and C30A/C115A--a marginally stable state in folded proteins.
AB  - Our earlier NMR study showed that a two-disulfide variant of hen lysozyme
      containing intra-alpha-domain disulfide bridges, C6-C127 and C30-C115, is
      partially folded, with the alpha domain tightly folded to the nativelike
      conformation and the beta domain flexible or unfolded. With a view that the
      formation of a third disulfide bridge is a key for the accomplishment of the
      overall chain fold, three-dimensional structures of three-disulfide variants of
      hen lysozyme lacking one disulfide bridge (C64A/C80A, C76A/C94A, and C30A/C115A)
      were studied in detail using NMR spectroscopy. Amide hydrogen exchange rates were
      measured to estimate the degree of conformational fluctuation in a residue
      specific manner. The structure of C76A/C94A was found to be quite similar to that
      of the wild type, except for the peptide segment of residues 74-78. The structure
      of C64A/C80A was considerably disordered in the entire region of the loop
      (residues 62-79). Further, it was found that a network of hydrogen bonds within
      the beta sheet and the 3(10) helix in the beta domain were disrupted and
      fluctuating. In C30A/C115A, the D helix was unstructured and the interface of the
      B helix with the D helix was significantly perturbed. However, the structural
      disorder generated in the hydrophobic core of the alpha domain was prevented by
      the C helix from propagating toward the beta domain. A marginally stable state in
      folded proteins is discussed based on the structures remaining in each three
      disulfide variant.

PMID- 15157101
TI  - Crystal structure of the C-terminal domain of the two-component system
      transmitter protein nitrogen regulator II (NRII; NtrB), regulator of nitrogen
      assimilation in Escherichia coli.
AB  - The kinase/phosphatase nitrogen regulator II (NRII, NtrB) is a member of the
      transmitter protein family of conserved two-component signal transduction
      systems. The kinase activity of NRII brings about the phosphorylation of the
      transcription factor nitrogen regulator I (NRI, NtrC), causing the activation of
      Ntr gene transcription. The phosphatase activity of NRII results in the
      inactivation of NRI-P. The activities of NRII are regulated by the signal
      transduction protein encoded by glnB, PII protein, which upon binding to NRII
      inhibits the kinase and activates the phosphatase activity. The C-terminal ATP
      binding domain of NRII is required for both the kinase and phosphatase activities
      and contains the PII binding site. Here, we present the crystal structure of the
      C-terminal domain of a mutant form of NRII, NRII-Y302N, at 1.6 A resolution and
      compare this structure to the analogous domains of other two-component system
      transmitter proteins. While the C-terminal domain of NRII shares the general
      tertiary structure seen in CheA, PhoQ, and EnvZ transmitter proteins, it contains
      a distinct beta-hairpin projection that is absent in these related proteins. This
      projection is near the site of a well-characterized mutation that reduces the
      binding of PII and near other less-characterized mutations that affect the
      phosphatase activity of NRII. Sequence alignment suggests that the beta-hairpin
      projection is present in NRII proteins from various organisms, and absent in
      other transmitter proteins from Escherichia coliK-12. This unique structural
      element in the NRII C-terminal domain may play a role in binding PII or in
      intramolecular signal transduction.

PMID- 15157102
TI  - Role of binding site loops in controlling nitric oxide release: structure and
      kinetics of mutant forms of nitrophorin 4.
AB  - Nitrophorins are ferric heme proteins that transport nitric oxide (NO) from blood
      sucking insects to victims. NO binding is tighter at lower pH values, as found in
      the insect salivary gland, and weaker at the pH of the victim's tissue,
      facilitating NO release and subsequent vasodilation. Previous structural analyses
      of nitrophorin 4 (NP4) from Rhodnius prolixus revealed a substantial NO-induced
      conformational change involving the A-B and G-H loops, which rearrange to
      desolvate the distal pocket and pack nonpolar residues against the heme-ligated
      NO. Previous kinetic analyses revealed a slow, biphasic, and pH-dependent NO
      release, which was proposed to be associated with loop movements. In this study,
      we created NP4 mutants D30A and D30N (A-B loop), D129A/L130A (G-H loop), and
      T121V (distal pocket). Eight crystal structures were determined, including
      complexes with NO, NH(3), and imidazole, to resolutions as high as 1.0 A. The NO
      induced conformational change is largely abolished in the loop mutants, but
      retained in T121V. Kinetic analyses using stopped-flow spectroscopy revealed the
      pH dependence for NO release is eliminated for D129A/L130A, considerably reduced
      for D30A and D30N, but retained for T121V. NO association rates were increased 2
      5-fold for T121V, but were unchanged in the loop mutants. Taken together, our
      findings demonstrate that the pH dependency for NO release is linked to loop
      dynamics and that solvent reorganization is apparently rate-limiting for
      formation of the initial iron-nitrosyl bond. Interestingly, the multiphasic
      kinetic behavior of rNPs was not affected by mutations, and its cause remains
      unclear.

PMID- 15157103
TI  - Multiplicity of strand incision at G:T base mismatches in DNA by human cell
      extracts.
AB  - Cell extract from the HT29 human colon carcinoma cell line (lacking mutator
      phenotype) was used to study the ATP-dependent G:T mismatch repair. We found that
      when a 45-bp (model) DNA with a single CpG/TpG mispair was incubated with the
      cell extract and ATP, it was incised immediately 5' and 3' to the mismatched T,
      and we noted that the actual 5'- and 3'-labeled fragments were similar to the
      cleaved products of thymine DNA glycosylase (TDG). This TDG-like cleavage product
      was enhanced (5-fold) with stimulation of several novel fragments, as inferred
      from the effect on incision at CpG/TpG site of the addition of G:U competitor DNA
      and ATP to the HT29 extract. The novel fragments were compatible with a strand
      incision on both sides of the mismatch (the third phosphodiester bond 5' and the
      second phosphodiester bond 3' to the mismatched T) and an incision 3' to the
      mismatched T, respectively. This suggests that while the ATP-dependent (TDG-like)
      incision activity, contrary to expectation, shows a lack of substrate
      competition, its catalytic property is likely modified by an interaction with G:U
      mispair. These multiple ATP-dependent incision events were not detected when
      extracts of the mismatch repair (MMR) defective HCT15 or HCT116 cell line were
      augmented with ATP and G:U. We postulate that these multiple ATP-dependent
      incision events possibly require the same MMR factors, and together they
      constitute a modified single ATP-dependent G:T incision activity. This activity
      toward the CpG/TpG was competitively inhibited by a 45-bp DNA with an ApG/TpT
      mispair; incision at a single site 5' to the latter mismatch compares with one of
      the multiple sites incised 5' to the former mismatch. These results suggest that
      one of several mismatch-incision factors is required by the human ATP-dependent
      G:T incision activity, in addition to MMR factors and ATP.

PMID- 15157105
TI  - DNA sequence alterations affect nucleosome array formation of the chicken
      ovalbumin gene.
AB  - The role of the large amount (more than half of the genome) of noncoding DNA in
      higher organisms is not well understood. DNA evolved to function in the context
      of chromatin, and the possibility exists that some of the noncoding DNA serves to
      influence chromatin structure and function. In this age of genomics and
      bioinformatics, genomic DNA sequences are being searched for informational
      content beyond the known genetic code. The discovery that period-10 non-T, A/T, G
      (VWG) triplets are among the most abundant motifs in human genomic DNA suggests
      that they may serve some function in higher organisms. In this paper, we provide
      direct evidence that the regular oscillation of period-10 VWG that occurs in the
      chicken ovalbumin gene sequence with a dinucleosome-like period facilitates
      nucleosome array formation. Using a linker histone-dependent in vitro chromatin
      assembly system that spontaneously aligns nucleosomes into a physiological array,
      we show that nucleosomes tend to avoid DNA regions with low period-10 VWG counts.
      This avoidance leads to the formation of an array with a nucleosome repeat equal
      to half the period value of the oscillation in period-10 VWG, as determined by
      Fourier analysis. Two different half-period deletions in the wild-type DNA
      sequence altered the nucleosome array, as predicted computationally. In contrast,
      a full-period deletion had an insignificant effect on the nucleosome array
      formed, also consistent with the prediction. An inversion mutation, with no DNA
      sequences deleted, again altered the nucleosome array formed, as predicted
      computationally. Hence, a VWG dinucleosome signal is plausible.

PMID- 15157104
TI  - Estrogen receptor-independent catechol estrogen binding activity: protein binding
      studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.
AB  - Primary evidence for novel estrogen signaling pathways is based upon well
      documented estrogenic responses not inhibited by estrogen receptor antagonists.
      In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has
      been shown to elicit biological responses independent of classical estrogen
      receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our
      research was designed to biochemically characterize the protein(s) that could be
      mediating the biological effects of catechol estrogens using enzymatically
      synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses
      identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable
      cytosolic binding sites in several ERalphaKO estrogen-responsive tissues.
      Specific catechol estrogen binding was competitively inhibited by unlabeled
      catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI
      182,780. Tissue distribution studies indicated significant binding differences
      both within and among various tissues in wild-type, ERalphaKO, and aromatase
      knockout female mice. Ligand metabolism experiments revealed extensive metabolism
      of labeled catechol estrogen, suggesting that catechol estrogen metabolites were
      responsible for the specific binding. Collectively, our data provide compelling
      evidence for the interaction of catechol estrogen metabolites with a novel
      binding protein that exhibits high affinity, specificity, and selective tissue
      distribution. The extensive biochemical characterization of this binding protein
      indicates that this protein may be a receptor, and thus may mediate ERalpha/beta
      independent effects of catechol estrogens and their metabolites.

PMID- 15157106
TI  - Mutagenic effects of 2-deoxyribonolactone in Escherichia coli. An abasic lesion
      that disobeys the A-rule.
AB  - Abasic sites are often referred to as noninstructive lesions. The C1'-oxidized
      abasic site (2-deoxyribonolactone, L) is produced by several DNA damaging agents,
      including gamma-radiolysis and the neocarzinostatin chromophore (NCS). The
      effects of a C1'-oxidized abasic site incorporated at a defined site in single
      stranded plasmid were examined in SOS polymerase-proficient and -deficient
      Escherichia coli. For comparison, experiments utilizing plasmids containing an
      abasic site (AP) were carried out side by side. In contrast to plasmid containing
      AP, dA and dG were incorporated most often when plasmid containing L was
      replicated. The ratio of dG:dA incorporation depended upon local sequence and
      varied from 0.9 to 2.2. High levels of translesion incorporation of dA are
      consistent with previous observations that treatment of DNA with the
      neocarzinostatin chromophore resulted in large amounts of G.C --> A.T transitions
      [Povirk and Goldberg (1986) Nucleic Acids Res. 14, 1417] and support the proposal
      that L is the source of these mutations. Both abasic lesions were 100% lethal in
      triple knockout cells lacking pol II, pol IV, and pol V. Analysis of translesion
      synthesis in repair-deficient cells revealed that pol V played a significant role
      in replication of L and AP. Significant levels of -1 frameshifts were formed in
      5'-d(CL) sequences in the presence of pol V and were the exclusive product in pol
      V-deficient cells. Frameshift products were not formed when the nucleotide on the
      5'-side of L was either dT or dG. Deleting pol II or pol IV had only modest
      effects on replication of L-containing plasmid but significantly decreased the
      amount of -1 frameshift product formed from an AP lesion. Experiments carried out
      side by side using otherwise identical plasmids containing an AP site illustrate
      the distinct properties of these two abasic lesions and that neither should be
      thought of as noninstructive.

PMID- 15157107
TI  - Translational control of apolipoprotein B mRNA: regulation via cis elements in
      the 5' and 3' untranslated regions.
AB  - Translational control of apolipoprotein B (apoB) mRNA has been previously
      documented; however, the molecular mechanisms that govern translation of apoB
      mRNA are unknown. We investigated the role of the untranslated regions (UTR) in
      the regulation of apoB mRNA translation first by analyzing apoB UTR sequences
      using M-fold, a program used to predict RNA secondary structure. M-fold analysis
      revealed hairpin-like elements within the 5'UTR and 3'UTR of apoB mRNA with
      potential to form stable secondary structure. Luciferase (LUC) reporter assays
      were conducted to assess the biological activity of the putative RNA motifs
      within the UTR sequences by transiently transfecting HepG2 cells with chimeric
      mRNAs containing the 5' and/or 3' apoB UTRs linked to a LUC reporter gene. We
      observed statistically significant increases in LUC activity for the 5'UTRpGL3
      and 5'/3'UTRpGL3 constructs. LUC mRNA levels remained constant for all
      constructs, suggesting that increased LUC activity was likely posttranscriptional
      in nature. When RNA isolated from transfected cells was translated in vitro,
      parallel increases in translatable LUC activity were observed. We also examined
      the role of UTR sequences within the context of the apoB coding sequence, using
      constructs containing the N-terminal 15% of apoB (apoB15). We observed a 40% and
      25% increase in total protein mass with the 5'UTR-apoB15 construct and the 5'UTR
      apoB15-3'UTR, respectively, over the control construct with no apoB UTR, with
      only a slight stimulation observed for apoB15 3'UTR. Radiolabeling analysis of
      apoB15 synthetic rate showed a more striking 4.5-fold stimulation of protein
      synthesis by 5'UTR while addition of both UTRs caused a 3.1-fold stimulation over
      the control construct. Deletion mutant analysis revealed that the stimulatory
      effect of the 5'UTR on apoB mRNA translation may be dependent on specific hairpin
      elements formed within the 5'UTR secondary structure. Overall, our data suggest
      that putative 5'UTR motifs are important for optimal translation of the apoB
      message whereas the presence of the 3'UTR appears to attenuate wild-type
      expression. Potential cis-trans interactions of these motifs with putative RNA
      binding proteins/translational factors are likely to govern apoB mRNA translation
      and protein synthesis and may play an important role in dysregulation of
      atherogenic lipoprotein production in dyslipidemic states.

PMID- 15157108
TI  - LC-MS/MS identification and yeast polymerase eta bypass of a novel gamma
      irradiation-induced intrastrand cross-link lesion G[8-5]C.
AB  - Reactive oxygen species can give rise to intrastrand cross-link lesions, where
      two neighboring nucleobases are covalently bonded. Here, we employed LC-MS/MS and
      demonstrated for the first time that gamma irradiation of a synthetic duplex
      oligodeoxyribonucleotide can give rise to an intrastrand cross-link lesion G[8
      5]C, where the C8 carbon atom of guanine and the C5 carbon atom of its 3'
      neighboring cytosine are covalently bonded. We also carried out in vitro
      replication studies of a substrate containing a site-specifically incorporated
      G[8-5]C, and our results showed that yeast Saccharomyces cerevisiae DNA
      polymerase eta (pol eta) was able to replicate past the cross-link lesion. Steady
      state kinetic analyses for nucleotide incorporation by pol eta showed that the 3'
      cytosine moiety of the cross-link did not significantly affect either the
      efficiency or the fidelity of nucleotide incorporation. The 5' guanine portion of
      the cross-link lesion, however, markedly reduced both the efficiency and the
      fidelity of nucleotide incorporation; the insertion of dGMP or dAMP was slightly
      favored over the insertion of the correct nucleotide, dCMP, which was in turn
      favored over the insertion of dTMP. The above results support that the oxidative
      cross-link lesion, if not repaired, can be mutagenic.

PMID- 15157109
TI  - Pre-steady-state kinetic studies of the fidelity and mechanism of polymerization
      catalyzed by truncated human DNA polymerase lambda.
AB  - DNA polymerase lambda (Pollambda), a member of the X-family DNA polymerases,
      possesses an N-terminal BRCT domain, a proline-rich domain, and a C-terminal
      polymerase beta-like domain (tPollambda). In this paper, we determined a minimal
      kinetic mechanism and the fidelity of tPollambda using pre-steady-state kinetic
      analysis of the incorporation of a single nucleotide into a one-nucleotide gapped
      DNA substrate, 21-19/41-mer (primer-primer/template). Our kinetic studies
      revealed an incoming nucleotide bound to the enzyme.DNA binary complex at a rate
      constant of 1.55 x 10(8) M(-1) s(-1) to form a ground-state ternary complex while
      the nucleotide dissociated from this complex at a rate constant of 300 s(-1).
      Since DNA dissociation from tPollambda (0.8 s(-1)) was less than 3-fold slower
      than polymerization, we measured saturation kinetics for all 16 possible
      nucleotide incorporations under single turnover conditions to eliminate the
      complication resulting from multiple turnovers. The fidelity of tPollambda was
      estimated to be in the range of 10(-2)-10(-4) and was sequence-dependent.
      Surprisingly, the ground-state binding affinity of correct (1.1-2.4 microM) and
      incorrect nucleotides (1.4-8.4 microM) was very similar while correct nucleotides
      (3-6 s(-1)) were incorporated much faster than incorrect nucleotides (0.001-0.2
      s(-1)). Interestingly, the misincorporation of dGTP opposite a template base
      thymine (0.2 s(-1)) was more rapid than all other misincorporations, leading to
      the lowest fidelity (3.2 x 10(-2)) among all mismatched base pairs. Additionally,
      tPollambda was found to possess weak strand-displacement activity during
      polymerization. These biochemical properties suggest that Pollambda likely fills
      short-patched DNA gaps in base excision repair pathways and participates in
      mammalian nonhomologous end-joining pathways to repair double-stranded DNA
      breaks.

PMID- 15157110
TI  - The stereoselectivity and catalytic properties of Xanthobacter autotrophicus 2
      [(R)-2-Hydroxypropylthio]ethanesulfonate dehydrogenase are controlled by
      interactions between C-terminal arginine residues and the sulfonate of coenzyme
      M.
AB  - 2-[(R)-2-Hydroxypropylthio]ethanesulfonate (R-HPC) dehydrogenase (DH) catalyzes
      the reversible oxidation of R-HPC to 2-(2-ketopropylthio)ethanesulfonate (2-KPC)
      in a key reaction in the bacterial conversion of chiral epoxides to beta-keto
      acids. R-HPCDH is highly specific for the R-enantiomer of HPC, while a separate
      enzyme, S-HPCDH, catalyzes the oxidation of the corresponding S-enantiomer. In
      the present study, the features of substrate and enzyme imparting
      stereospecificity have been investigated for R-HPCDH. S-HPC was a substrate for R
      HPCDH with a K(m) identical to that for R-HPC but with a k(cat) 600 times lower.
      Achiral 2-propanol and short-chain (R)- and (S)-2-alkanols were substrates for R
      HPCDH. For (R)-alkanols, as the carbon chain length increased, K(m) decreased,
      with the K(m) for (R)-2-octanol being 1700 times lower than for 2-propanol. At
      the same time, k(cat) changed very little and was at least 90% lower than k(cat)
      for R-HPC and at least 22 times higher than k(cat) for S-HPC. (S)-2-Butanol and
      (S)-2-pentanol were substrates for R-HPCDH. The K(m) for (S)-2-butanol was
      identical to that for (R)-2-butanol, while the K(m) for (S)-2-pentanol was 7.5
      times higher than for (R)-2-pentanol. Longer chain (S)-2-alkanols were
      sufficiently poor substrates for R-HPCDH that kinetic parameters could not be
      determined. Mutagenesis of C-terminal arginine residues of R-HPCDH revealed that
      R152 and R196 are essential for effective catalysis with the natural substrates R
      HPC and 2-KPC but not for catalysis with 2-alkanols or ketones as substrates.
      Short-chain alkylsulfonates and coenzyme M (2-mercaptoethanesulfonate) were found
      to modify the kinetic parameters for 2-butanone reduction by R-HPCDH in a
      saturable fashion, with the general effect of increasing k(cat), decreasing K(m),
      and increasing the enantioselectivity of 2-butanone reduction to a theoretical
      value of 100% (S)-2-butanol. The modulating effects of ethanesulfonate and
      propanesulfonate provided thermodynamic binding constants close to K(m) for the
      natural substrates R-HPC and 2-KPC. The effects of alkylsulfonates on modulating
      the enantioselectivity and kinetic properties of R-HPCDH were abolished in R152A
      and R196A mutants but not in mutants of other C-terminal arginine residues.
      Collectively, the results suggest that interactions between the sulfonate of CoM
      and specific arginine residues are key to the enantioselectivity and catalytic
      efficiency of R-HPCDH. A model is proposed wherein sulfonate-arginine
      interactions within an alkylsulfonate binding pocket control the catalytic
      properties of R-HPCDH.

PMID- 15157111
TI  - Iron bound to the high-affinity Mn-binding site of the oxygen-evolving complex
      shifts the pK of a component controlling electron transport via Y(Z).
AB  - Flash-probe fluorescence spectroscopy was used to compare the pH dependence of
      charge recombination between Y(Z)(*) and Q(a)(-) in Mn-depleted, photosystem II
      membranes [PSII(-Mn)] and in membranes with the high-affinity (HA(Z)) Mn-binding
      site blocked by iron [PSII(-Mn,+Fe); Semin, B. K., Ghirardi, M. L., and Seibert,
      M. (2002) Biochemistry 41, 5854-5864]. The apparent half-time for fluorescence
      decay (t(1/2)) in PSII(-Mn) increased from 9 ms at pH 4.4 to 75 ms at pH 9.0
      [with an apparent pK (pK(app)) of 7.1]. The actual fluorescence decay kinetics
      can be fit to one exponential component at pH <6.0 (t(1/2) = 9.5 ms), but it
      requires an additional component at pH >6.0 (t(1/2) = 385 ms). Similar
      measurements with PSII(-Mn,+Fe) membranes show that iron binding has little
      effect on the maximum and minimum t(1/2) values measured at alkaline and acidic
      pHs but that it does shift the pK(app) from 7.1 to 6.1 toward the more acidic
      pK(app) value typical of intact membranes. Light-induced Fe(II) blocking of the
      PSII(-Mn) membrane is accompanied by a decrease in buffer Fe(II) concentration.
      This decrease was not the result of Fe(II) binding, but rather of its oxidation
      at two sites, the HA(Z) site and the low-affinity site. Mossbauer spectroscopy at
      80 K on PSII(-Mn,+Fe) samples, prepared under conditions providing the maximal
      blocking effect but minimizing the amount of nonspecifically bound iron cations,
      supports this conclusion since this method detected only Fe(III) cations bound to
      the membranes. Correlation of the kinetics of Fe(II) oxidation with the blocking
      parameters showed that blocking occurs after four to five Fe(II) cations were
      oxidized at the HA(Z) site. In summary, the blocking of the HA(Z) Mn-binding site
      by iron in PSII(-Mn) membranes not only prevents the access of exogenous donors
      to Y(Z) but also partially restores the properties of the hydrogen bond net found
      in intact PS(II), which in turn controls the rate of electron transport to Y(Z).

PMID- 15157112
TI  - Hydroxyl radical generation by photosystem II.
AB  - The photogeneration of hydroxyl radicals (OH(*)) in photosystem II (PSII)
      membranes was studied using EPR spin-trapping spectroscopy. Two kinetically
      distinguishable phases in the formation of the spin trap-hydroxyl (POBN-OH)
      adduct EPR signal were observed: the first phase (t(1/2) = 7.5 min) and the
      second phase (t(1/2) = 30 min). The generation of OH(*) was found to be
      suppressed in the absence of the Mn-complex, but it was restored after readdition
      of an artificial electron donor (DPC). Hydroxyl radical generation was also lost
      in the absence of oxygen, whereas it was stimulated when the oxygen concentration
      was increased. The production of OH(*) during the first kinetic phase was
      sensitive to the presence of SOD, whereas catalase and EDTA diminished the
      production of OH(*) during the second kinetic phase. The POBN-OH adduct EPR
      signal during the first phase exhibits a similar pH-dependence as the ability to
      oxidize the non-heme iron, as monitored by the Fe(3+) (g = 8) EPR signal: both
      EPR signals gradually decreased as the pH value was lowered below pH 6.5 and were
      absent at pH 5. Sodium formate decreases the production of OH(*) in intact and Mn
      deleted PSII membranes. Upon illumination of PSII membranes, both superoxide, as
      measured by EPR signal from the spin trap-superoxide (EMPO-OOH) adduct, and
      H(2)O(2), measured colormetrically, were generated. These results indicated that
      OH(*) is produced on the electron acceptor side of PSII by two different routes,
      (1) O(2)(*)(-), which is generated by oxygen reduction on the acceptor side of
      PSII, interacts with a PSII metal center, probably the non-heme iron, to form an
      iron-peroxide species that is further reduced to OH(*) by an electron from PSII,
      presumably via Q(A)(-), and (2) O(2)(*)(-) dismutates to form free H(2)O(2) that
      is then reduced to OH(*) via the Fenton reaction in the presence of metal ions,
      the most likely being Mn(2+) and Fe(2+) released from photodamaged PSII. The two
      different routes of OH(*) generation are discussed in the context of
      photoinhibition.

PMID- 15157113
TI  - Transmembrane domain 5 of the LdNT1.1 nucleoside transporter is an amphipathic
      helix that forms part of the nucleoside translocation pathway.
AB  - Transporters of the equilibrative nucleoside transporter (ENT) family promote the
      uptake of nucleosides, nucleobases, and a variety of therapeutic drugs in
      eukaryotes from protozoa to mammals. Despite its importance, the translocation
      pathway that mediates the internalization of these substrates has not been
      identified yet in any of the ENT carriers. Previous genetic studies on the
      LdNT1.1 nucleoside transporter from Leishmania donovani defined two amino acid
      residues in predicted transmembrane domains (TMD) 5 and 7 that may line this
      translocation pathway. The role of TMD5 in forming a portion of the aqueous
      channel was investigated using the substituted-cysteine accessibility method. A
      series of 22 cysteine substitution mutants spanning predicted TMD5 were created
      from a fully functional, cysteine-less, parental LdNT1.1. Cysteine replacement at
      six positions (M(176)C, T(186)C, S(187)C, Q(190)C, V(193)C, and K(194)C) produced
      permeases that were inhibited by incubation with sulfhydryl-specific
      methanethiosulfonate reagents, denoting their solvent accessibility to the
      translocation pathway. Adenosine was able to block this thiol modification,
      implying that access to the domain becomes restricted as a consequence of the
      substrate binding. Strikingly, the Q(190)C substitution interacted differentially
      with the substrates adenosine and uridine, suggesting that binding of adenosine
      but not uridine might directly occlude this position. When superimposed on a
      helical model, all six mutants clustered along one face of the amphipathic alpha
      helix predicted for TMD5, strongly suggesting its involvement in the
      translocation pathway through LdNT1.1.

PMID- 15157114
TI  - Circumnavigating misfolding traps in the energy landscape through protein
      engineering: suppression of molten globule and aggregation in carbonic anhydrase.
AB  - The native state of the enzyme human carbonic anhydrase (HCA II) has been
      stabilized by the introduction of a disulfide bond, the oxidized A23C/L203C
      mutant. This stabilized protein variant undergoes an apparent two-state unfolding
      process with suppression of the otherwise stable equilibrium, molten-globule
      intermediate, which is normally very prone to aggregation. Stopped-flow
      measurements also showed that lower amounts of the transiently occurring molten
      globule were formed during refolding. This led to a markedly lowered tendency for
      aggregation during equilibrium denaturing conditions and, more importantly, to
      significantly higher reactivation yields upon refolding of the fully denatured
      protein. Thus, a general strategy to circumvent aggregation during the refolding
      of proteins could be to stabilize the native state of a protein at the expense of
      partially folded intermediates, thereby shifting the unfolding behavior from a
      three-state process to a two-state one.

PMID- 15157115
TI  - Reactions of H2, CO, and O2 with active [NiFe]-hydrogenase from Allochromatium
      vinosum. A stopped-flow infrared study.
AB  - The Ni-Fe site in the active membrane-bound [NiFe]-hydrogenase from
      Allochromatium vinosum can exist in three different redox states. In the most
      oxidized state (Ni(a)-S) the nickel is divalent. The most reduced state (Ni(a)
      SR) likewise has Ni(2+), while the intermediate state (Ni(a)-C) has Ni(3+). The
      transitions between these states have been studied by stopped-flow Fourier
      transform infrared spectroscopy. It is inferred from the data that the Ni(a)-S -
      > Ni(a)-C* and Ni(a)-C* --> Ni(a)-SR transitions induced by dihydrogen require
      one of the [4Fe-4S] clusters to be oxidized. Enzyme in the Ni(a)-S* state with
      all of the iron-sulfur clusters reduced reacts with dihydrogen to form the Ni(a)
      SR state in milliseconds. By contrast, when one of the cubane clusters is
      oxidized, the Ni(a)-S state reacts with dihydrogen to form the Ni(a)-C state with
      all of the iron-sulfur clusters reduced. The competition between dihydrogen and
      carbon monoxide for binding to the active site was dependent on the redox state
      of the nickel ion. Formation of the Ni(a)-S.CO state (Ni(2+)) by reacting CO with
      enzyme in the Ni(a)-SR and Ni(a)-S states (Ni(2+)) is considerably faster than
      its formation from enzyme in the Ni(a)-C* (Ni(3+)) state. Excess oxygen converted
      hydrogen-reduced enzyme to the inactive Ni(r)* state within 158 ms, suggesting a
      direct reaction at the Ni-Fe site. With lower O(2) concentrations the formation
      of intermediate states was observed. The results are discussed in the light of
      the present knowledge of the structure and mechanism of action of the A. vinosum
      enzyme.

PMID- 15157116
TI  - Hydrogen-induced activation of the [NiFe]-hydrogenase from Allochromatium vinosum
      as studied by stopped-flow infrared spectroscopy.
AB  - The reaction between hydrogen and the [NiFe]-hydrogenase from Allochromatium
      vinosum in its inactive form has been studied by stopped-flow infrared
      spectroscopy. The data, for the first time, clearly show that at room temperature
      enzyme in the unready state, either oxidized or reduced, does not react with
      hydrogen. Enzyme in the ready state reacts with hydrogen after a lag phase of
      about six seconds, whereby a specific reduction of the enzyme occurs. The lag
      phase and the rate of reduction of the ready enzyme are neither dependent on the
      enzyme concentration nor on the substrate concentration, i.e., substoichiometric
      and 8-fold excess amounts of H(2) reduce the ready enzyme at the same rate.
      Oxygen delays this reaction but does not prevent it. The infrared changes lead us
      to suggest that the hydroxyl group, bridging between the Ni and the Fe atom in
      the active site, becomes protonated during this reduction. At physiological
      temperatures, this property of the inactive ready enzyme enables a full
      development of activity by substoichiometric H(2) concentrations.

PMID- 15157119
TI  - The application of risk management in sport.
AB  - The process of risk management can be implemented as part of a best practice
      management system within the sport and leisure sector. The process enables risk
      factors that might lead to injuries to be identified and the levels of risk
      associated with activities to be estimated and evaluated. This information can be
      utilised proactively by sports governing bodies and participants to identify
      preventive and therapeutic interventions in order to reduce the frequency of
      occurrence and/or severity of injuries within their sports. The acceptability of
      risk within specific sports, however, is dependent on the perceptions of the
      participants involved.

PMID- 15157120
TI  - Gene doping in sports.
AB  - Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non
      therapeutic use of genes, genetic elements and/or cells that have the capacity to
      enhance athletic performance". New research in genetics and genomics will be used
      not only to diagnose and treat disease, but also to attempt to enhance human
      performance. In recent years, gene therapy has shown progress and positive
      results that have highlighted the potential misuse of this technology and the
      debate of 'gene doping'. Gene therapies developed for the treatment of diseases
      such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for
      insulin-like growth factor-1) and peripheral vascular diseases (the gene for
      vascular endothelial growth factor) are potential doping methods. With progress
      in gene technology, many other genes with this potential will be discovered. For
      this reason, it is important to develop timely legal regulations and to research
      the field of gene doping in order to develop methods of detection. To protect the
      health of athletes and to ensure equal competitive conditions, the International
      Olympic Committee, WADA and International Sports Federations have accepted
      performance-enhancing substances and methods as being doping, and have forbidden
      them. Nevertheless, the desire to win causes athletes to misuse these drugs and
      methods. This paper reviews the current status of gene doping and candidate
      performance enhancement genes, and also the use of gene therapy in sports
      medicine and ethics of genetic enhancement.

PMID- 15157121
TI  - Exercise and prostate cancer.
AB  - Prostate cancer is a leading cause of cancer morbidity and mortality in men. In
      addition to improved treatments, strategies to reduce disease risk are urgently
      required. This review summarises the literature that examines the association
      between exercise and prostate cancer risk. Between 1989 and 2001, 13 cohort
      studies were conducted in the US and internationally. Of these, nine showed an
      association between exercise and decreased prostate cancer risk. Five of 11 case
      control studies conducted between 1988 and 2002 reported an association between
      decreased risk of prostate cancer and high activity levels. Considering all
      studies performed between 1976 and 2002, 16 out of 27 studies reported reduced
      risk in men who were most active; in nine out of 16 studies the reduction in risk
      was statistically significant. Average risk reduction ranged from 10-30%. In
      aggregate, this evidence suggests a probable link between increased physical
      exercise and decreased prostate cancer risk. The ability of exercise to modulate
      hormone levels, prevent obesity, enhance immune function and reduce oxidative
      stress have all been postulated as mechanisms that may underlie the protective
      effect of exercise. Exercise may also be of benefit in men undergoing treatment
      for prostate cancer. Overall, study design and control of potential confounding
      factors varied greatly among studies, possibly contributing to the variation in
      results. Epidemiological studies that are better controlled, larger in scale and
      more carefully designed may help to more fully clarify the relationship between
      exercise and prostate cancer. In addition, intervention trials that test whether
      exercise programmes can reduce prostate cancer risk are currently underway to
      rigorously test the ability of exercise to reduce prostate cancer incidence.

PMID- 15157123
TI  - Effect of virtual reality graded exposure on anxiety levels of performing
      musicians: a case study.
AB  - This study examined the effect of computer generated virtual reality graded
      exposure on the physiological and psychological responses of performing
      musicians. Three upper division undergraduate saxophonists, two female and one
      male, performed while immersed in four virtual environments each designed to
      gradually increase the expected anxiety level of the performer. Heart rates and
      subjective measurements were taken throughout the exposure period. Results of
      this study indicated that virtual reality graded exposure did elicit
      physiological and psychological indications of increased anxiety in musical
      performance environments designed for that purpose. Findings also corroborated
      previous research that found gender to be a predictor of heart rate during
      performance.

PMID- 15157124
TI  - Assessment of use of music by patients participating in cardiac rehabilitation.
AB  - The primary cause of morbidity and mortality in the United States is heart
      disease. It is a costly and pervasive group of disorders that effect all ages,
      races, and genders. Behavioral medicine and health psychology have focused on
      prevention and psychosocial influences of cardiovascular diseases for the past 30
      years. Music therapy is a viable collaborative method in the psychosocial arena
      for alleviating risks and motivating rehabilitation from cardiac events. There is
      research to support the use of music to modulate heart health measurements such
      as heart rate and blood pressure, to enhance exercise programs, and to relieve
      stress symptoms. However, inconsistencies in the results of this research warrant
      continued collaboration of social scientists to find scientific means of
      establishing interventions with measurable outcomes. This project involved
      administering a music therapy survey in order to determine current use and
      preference for music in a cardiac rehabilitation program. Patients who were
      attending rehabilitation sessions in a large city hospital completed a survey on
      which they rated their level of use of music for exercise, relaxation, and
      enjoyment. The researcher also gathered information about musical preferences,
      musical experiences, and pertinent demographics. Patients, mostly white males
      over the age of 60, showed positive responses to the aesthetically pleasurable
      aspects of music. The use of music as a stimulus cue for exercise was decidedly
      absent. Nursing staff members were receptive to the project, and both staff and
      patients showed some interest for learning about music for therapeutic purposes.
      The results suggest that education about and development of music therapy in a
      cardiac rehabilitation program is warranted.

PMID- 15157125
TI  - Music therapy assessment for children with developmental disabilities: a survey
      study.
AB  - The purpose of this study was to survey music therapists working with children
      with developmental disabilities to examine and describe the following: (a) the
      major skill areas and subcategories most frequently assessed, (b) how these areas
      are assessed, (c) the common features of their current assessment tools, (d) the
      positive and/or negative aspects of their current assessment tools, and (e) the 3
      most important features desired in a standardized music therapy assessment for
      use in their clinical practice. Of the 207 respondents who expressed interest in
      completing a music therapy assessment survey in a pilot study, 108 surveys were
      returned for a 52% return rate; 95 (46%) were used as data for this study. The
      respondents most frequently assessed the following major skill areas: Motor
      (95%), Communication (83%), Social (79%), Cognitive (64%), and Music (35%). Of
      the 34 (36%) respondents who enclosed an actual assessment form with their
      survey, 100% require data collection through behavior observation. Respondents
      most frequently noted the following positive aspects of their forms: Thorough
      (34%), Individualized (26%), and Easy to Use (26%), and the following negative
      aspects of their forms: Subjective (28%), Limiting (26%), and Time Consuming
      (22%). The 3 most commonly desired features of a standardized assessment were the
      following: Easy to Use (23%), Comprehensive (19%), and Adaptable (13%).

PMID- 15157126
TI  - The effects of live music groups versus an educational children's television
      program on the emergent literacy of young children.
AB  - Research suggests that music is beneficial in teaching both social and academic
      skills to young children. The purpose of this study was to examine the effects of
      a music therapy program designed to teach reading skills versus the "Between the
      Lions" television program on the early literacy behaviors of Kindergarten
      children from a low socioeconomic background. Subjects (n = 86) were children,
      aged 5-7 years, enrolled in one of four different Kindergarten classes at a
      public elementary school in Northwest Florida. Each class was assigned one of
      four treatment conditions: Music/Video (sequential presentation of each
      condition), Music-Only, Video-Only, and no contact Control group. Growth in early
      literacy skills was measured using the Dynamic Indicators of Basic Early Literacy
      Skills (DIBELS) and 3 subtests of the Test of Early reading Ability-3rd edition
      (TERA-3). Teachers' perceptions of classroom literacy behaviors were measured
      using a pre and poststudy survey. This study also compared on- and off-task
      behavior of students during video versus music conditions. Results of the 7
      subtests measuring early literacy were varied. The Music/Video and Music-Only
      groups achieved the highest increases in mean scores from pre to posttest on 4 of
      the 7 subtests. Students in the Video-Only group scored significantly better on
      the phonemic segmentation portion of the DIBELS than peers in the Music/Video
      condition. Furthermore, strong correlations were found between the Letter Naming,
      Initial Sounds Fluency tests, and total raw score of the TERA-3 tests for both
      pre and posttesting. Additionally, graphic analysis of mean off-task behavior per
      session indicated that students were more off-task during both video conditions
      (video alone and video portion of Music/Video condition) than during the music
      conditions. Off-task behavior was consistently lower during music sessions for
      the duration of the study. This study confirmed that music increases the on-task
      behavior of students. Additionally, the combination of music and video enrichment
      showed gains in 4 of the 8 tests used to measure students' progress. This pattern
      supports the need for further investigation regarding benefits of enrichment
      programs specifically designed to enhance curricula for students from low
      socioeconomic backgrounds, particularly programs that incorporate music
      activities.

PMID- 15157127
TI  - Speech recognition in fluctuating and continuous maskers: effects of hearing loss
      and presentation level.
AB  - Listeners with normal-hearing sensitivity recognize speech more accurately in the
      presence of fluctuating background sounds, such as a single competing voice, than
      in unmodulated noise at the same overall level. These performance differences are
      greatly reduced in listeners with hearing impairment, who generally receive
      little benefit from fluctuations in masker envelopes. If this lack of benefit is
      entirely due to elevated quiet thresholds and the resulting inaudibility of low
      amplitude portions of signal + masker, then listeners with hearing impairment
      should derive increasing benefit from masker fluctuations as presentation levels
      increase. Listeners with normal-hearing (NH) sensitivity and listeners with
      hearing impairment (HI) were tested for sentence recognition at moderate and high
      presentation levels in competing speech-shaped noise, in competing speech by a
      single talker, and in competing time-reversed speech by the same talker. NH
      listeners showed more accurate recognition at moderate than at high presentation
      levels and better performance in fluctuating maskers than in unmodulated noise.
      For these listeners, modulated versus unmodulated performance differences tended
      to decrease at high presentation levels. Listeners with HI, as a group, showed
      performance that was more similar across maskers and presentation levels.
      Considered individually, only 2 out of 6 listeners with HI showed better overall
      performance and increasing benefit from masker fluctuations as presentation level
      increased. These results suggest that audibility alone does not completely
      account for the group differences in performance with fluctuating maskers;
      suprathreshold processing differences between groups also appear to play an
      important role. Competing speech frequently provided more effective masking than
      time-reversed speech containing temporal fluctuations of equal magnitude. This
      finding is consistent with "informational" masking resulting from competitive
      processing of words and phrases within the speech masker that would notoccur for
      time-reversed sentences.

PMID- 15157128
TI  - Effect of age on silent gap discrimination in synthetic speech stimuli.
AB  - The difficulty that older listeners experience understanding conversational
      speech may be related to their limited ability to use information present in the
      silent intervals (i.e., temporal gaps) between dynamic speech sounds. When
      temporal gaps are present between nonspeech stimuli that are spectrally invariant
      (e.g., noise bands or sinusoids), older listeners are less able to resolve
      temporal gaps than are younger listeners. It has also been demonstrated that
      temporal gap perception deteriorates as the frequency difference between the
      sounds bordering the silent gap increases, and this effect becomes more
      pronounced with age (J. Lister, J. Besing, and J. Koehnke, 2002; J. Lister, J.
      Koehnke, and J. Besing, 2000). In this study, the effect of age on the ability to
      discriminate temporal gaps in dynamic stimuli (i.e., changing in frequency and
      duration over time) was measured in a gap duration discrimination (GDD) task. The
      participants were two groups of listeners with normal hearing sensitivity through
      at least 4000 Hz: (a) ages 21-38 years and (b) ages 50-72 years. Stimuli
      simulated the frequency characteristics of 1 consonant (/s/), a steady-state
      vowel (/a/), a weak diphthong (/eI/), and a voiced bilabial plosive (/burst/) in
      6 combinations: (a) /s-a/, (b) /s-eI/, (c) /a-a/, (d) /eI-eI/, (e) /burst-a/, and
      (f) /burst-eI/. For each of the 6 phoneme combinations, 2 conditions of stimulus
      duration were used: (a) fixed, meaning that the durations of leading and trailing
      noises were fixed at values typical for the speech sounds being simulated, and
      (b) random, meaning that duration varied randomly within a range acceptable for
      accurate perception of the speech contrasts. Gap duration difference limens
      (GDDLs) were significantly larger for the older listeners than for younger
      listeners. For both groups, GDDLs were poorer for the spectrally dynamic marker
      pairs (e.g., /burst-eI/) than for the marker pairs that were relatively stable in
      frequency over time (/a-a/). GDD performance also was poorer for the random
      conditionthan for the fixed condition. Listener age and hearing sensitivity were
      significantly correlated, and age was not significantly correlated with GDD when
      controlling for hearing sensitivity. The authors conclude that temporal
      resolution (as measured by gap discrimination) is affected by age, stimulus
      complexity, and, perhaps, by hearing sensitivity in a speech context.

PMID- 15157129
TI  - The effect of asymmetrical signal degradation on binaural speech recognition in
      children and adults.
AB  - To determine the effect of asymmetrical signal degradation on binaural speech
      recognition, 28 children and 14 adults were administered a sentence recognition
      task amidst multitalker babble. There were 3 listening conditions: (a) monaural,
      with mild degradation in 1 ear; (b) binaural, with mild degradation in both ears
      (symmetric degradation); and (c) binaural, with mild degradation in one ear and
      severe degradation in the other ear (asymmetric degradation). Sentences and
      babble were degraded digitally to simulate mild and severe cochlear hearing loss.
      All participants demonstrated significant binaural advantage (average of 7 dB)
      when listening to symmetrically degraded signals as compared to when listening
      monaurally. In contrast, adults and children achieved little or no binaural
      benefit, on average, when listening to asymmetrically degraded signals. Moreover,
      overall performance of the adults was significantly worse when listening to
      binaural asymmetrically degraded signals than when listening to monaural signals,
      thus demonstrating evidence of binaural interference. In contrast to our original
      speculations, however, children did not show an overall demonstration of binaural
      interference. Relative performance in the binaural-asymmetric and the monaural
      conditions was not influenced by which ear (right or left) received the more
      degraded signal.

PMID- 15157130
TI  - Prevalence of voice disorders in teachers and the general population.
AB  - Over 3 million teachers in the United States use their voice as a primary tool of
      trade and are thought to be at higher risk for occupation-related voice disorders
      than the general population. However, estimates regarding the prevalence of voice
      disorders in teachers and the general population vary considerably. To determine
      the extent that teachers are at greater risk for voice disorders, 2,531 randomly
      selected participants from Iowa and Utah (1,243 teachers and 1,288 nonteachers)
      were interviewed by telephone using a voice disorder questionnaire. Prevalence
      the number of cases per population at risk at a specific time-was determined. The
      prevalence of reporting a current voice problem was significantly greater in
      teachers compared with nonteachers (11.0% vs. 6.2%), chi(2)(1) = 18.2, p <.001,
      as was the prevalence of voice disorders during their lifetime (57.7% for
      teachers vs. 28.8% for nonteachers), chi(2)(1) = 215.2, p <.001. Teachers were
      also significantly more likely than nonteachers to have consulted a physician or
      speech-language pathologist regarding a voice disorder (14.3% vs. 5.5%),
      chi(2)(1) = 55.3, p <.001. Women, compared with men, not only had a higher
      lifetime prevalence of voice disorders (46.3% vs. 36.9%), chi(2)(1) = 20.9, p
      <.001, but also had a higher prevalence of chronic voice disorders (>4 weeks in
      duration), compared with acute voice disorders (20.9% vs. 13.3%), chi(2)(1) =
      8.7, p =.003. To assess the association between past voice disorders and possible
      risks, adjusted odds ratios (ORs) were estimated using multiple logistic
      regression. The results identified that being a teacher, being a woman, being
      between 40 and 59 years of age, having 16 or more years of education, and having
      a family history of voice disorders were each positively associated with having
      experienced a voice disorder in the past. These results support the notion that
      teaching is a high-risk occupation for voice disorders. Important information is
      also provided regarding additional factors that might contribute to the
      development of voice disorders.

PMID- 15157131
TI  - Orofacial movements associated with fluent speech in persons who stutter.
AB  - This study was intended to replicate and extend previous findings that (a) during
      fluent speech persons who stutter (PS) and those who do not (NS) differ in their
      vocal tract closing movements (L. Max, A. J. Caruso, and V. L. Gracco, 2003) and
      (b) ratios relating lip and tongue speed to jaw speed increase with stuttering
      severity (M. D. McClean and C. R. Runyan, 2000). An electromagnetic system was
      used to record movements of the upper lip, lower lip, tongue, and jaw of 43 NS
      and 37 PS during productions of a nonsense phrase and a sentence. Measurement and
      analysis of movement speeds, durations, and ratios of lip and tongue speed to jaw
      speed were performed on fluent productions of a nonsense phrase and sentence.
      Statistical comparisons were made between PS with low and high stuttering
      severity levels (LPS and HPS) and NS. Significant variations across groups in
      movement speed and duration were observed, but the pattern of these effects was
      complex and did not replicate the results of the two earlier studies. In the
      nonsense phrase, significant reductions in lower lip closing duration, jaw
      closing duration, and jaw closing speed were seen in PS. In the sentence task,
      HPS showed elevated tongue opening and closing durations. For tongue opening in
      the sentence, LPS showed elevated speeds and HPS showed reduced speeds. The
      elevated speeds for LPS are interpreted as a contributing factor to speech
      disfluency, whereas the reduced speeds and increased durations in HPS are
      attributed to adaptive behavior intended to facilitate fluent speech. Significant
      group effects were not seen for the speed ratio measures. Results are discussed
      in relation to multivariate analyses intended to identify subgroups of PS.

PMID- 15157122
TI  - What is the relationship between exercise and metabolic abnormalities? A review
      of the metabolic syndrome.
AB  - Prevention of the metabolic syndrome and treatment of its main characteristics
      are now considered of utmost importance in order to combat the epidemic of type 2
      diabetes mellitus and to reduce the increased risk of cardiovascular disease and
      all-cause mortality. Insulin resistance/hyperinsulinaemia are consistently linked
      with a clustering of multiple clinical and subclinical metabolic risk factors. It
      is now widely recognised that obesity (especially abdominal fat accumulation),
      hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that,
      concurrently, constitute the distinctive insulin resistance or metabolic
      syndrome. Cross-sectional and prospective data provide an emerging picture of
      associations of both physical activity habits and cardiorespiratory fitness with
      the metabolic syndrome. The metabolic syndrome, is a disorder that requires
      aggressive multi-factorial intervention. Recent treatment guidelines have
      emphasised the clinical utility of diagnosis and an important treatment role for
      'therapeutic lifestyle change', incorporating moderate physical activity. Several
      previous narrative reviews have considered exercise training as an effective
      treatment for insulin resistance and other components of the syndrome. However,
      the evidence cited has been less consistent for exercise training effects on
      several metabolic syndrome variables, unless combined with appropriate dietary
      modifications to achieve weight loss. Recently published randomised controlled
      trial data concerning the effects of exercise training on separate metabolic
      syndrome traits are evaluated within this review. Novel systematic review and
      meta-analysis evidence is presented indicating that supervised, long-term,
      moderate to moderately vigorous intensity exercise training, in the absence of
      therapeutic weight loss, improves the dyslipidaemic profile by raising high
      density lipoprotein-cholesterol and lowering triglycerides in overweight and
      obese adults with characteristics of the metabolic syndrome. Lifestyle
      interventions, including exercise and dietary-induced weight loss may improve
      insulin resistance and glucose tolerance in obesity states and are highly
      effective in preventing or delaying the onset of type 2 diabetes in individuals
      with impaired glucose regulation. Randomised controlled trial evidence also
      indicates that exercise training decreases blood pressure in overweight/obese
      individuals with high normal blood pressure and hypertension. These evidence
      based findings continue to support recommendations that supervised or partially
      supervised exercise training is an important initial adjunctive step in the
      treatment of individuals with the metabolic syndrome. Exercise training should be
      considered an essential part of 'therapeutic lifestyle change' and may
      concurrently improve insulin resistance and the entire cluster of metabolic risk
      factors.

PMID- 15157132
TI  - Using visible speech to train perception and production of speech for individuals
      with hearing loss.
AB  - The main goal of this study was to implement a computer-animated talking head,
      Baldi, as a language tutor for speech perception and production for individuals
      with hearing loss. Baldi can speak slowly; illustrate articulation by making the
      skin transparent to reveal the tongue, teeth, and palate; and show supplementary
      articulatory features, such as vibration of the neck to show voicing and
      turbulent airflow to show frication. Seven students with hearing loss between the
      ages of 8 and 13 were trained for 6 hours across 21 weeks on 8 categories of
      segments (4 voiced vs. voiceless distinctions, 3 consonant cluster distinctions,
      and 1 fricative vs. affricate distinction). Training included practice at the
      segment and the word level. Perception and production improved for each of the 7
      children. Speech production also generalized to new words not included in the
      training lessons. Finally, speech production deteriorated somewhat after 6 weeks
      without training, indicating that the training method rather than some other
      experience was responsible for the improvement that was found.

PMID- 15157133
TI  - Brain correlates of stuttering and syllable production: gender comparison and
      replication.
AB  - This article reports a gender replication study of the P. T. Fox et al. (2000)
      performance correlation analysis of neural systems that distinguish between
      normal and stuttered speech in adult males. Positron-emission tomographic (PET)
      images of cerebral blood flow (CBF) were correlated with speech behavior scores
      obtained during PET imaging for 10 dextral female stuttering speakers and 10
      dextral, age- and sex-matched normally fluent controls. Gender comparisons were
      made between the total number of voxels per region significantly correlated with
      speech performance (as in P. T. Fox et al., 2000) plus total voxels per region
      that were significantly correlated with stutter rate and not with syllable rate.
      Stutter-rate regional correlates were generally right-sided in males, but
      bilateral in the females. For both sexes the positive regional correlates for
      stuttering were in right (R) anterior insula and the negative correlates were in
      R Brodmann area 21/22 and an area within left (L) inferior frontal gyrus. The
      female stuttering speakers displayed additional positive correlates in L anterior
      insula and in basal ganglia (L globus pallidus, R caudate), plus extensive right
      hemisphere negative correlates in the prefrontal area and the limbic and parietal
      lobes. The male stuttering speakers were distinguished by positive correlates in
      L medial occipital lobe and R medial cerebellum. Regions that positively
      correlated with syllable rate (essentially stutter-free speech) in stuttering
      speakers and controls were very similar for both sexes. The findings strengthen
      claims that chronic developmental stuttering is functionally related to abnormal
      speech-motor and auditory region interactions. The gender differences may be
      related to differences between the genders with respect to susceptibility (males
      predominate) and recovery from chronic stuttering (females show higher recovery
      rates during childhood).

PMID- 15157134
TI  - Use of electromagnetic midsagittal articulography in the study of swallowing.
AB  - The tongue functions as the primary articulator during the oropharyngeal stages
      of swallowing. However, detailed descriptions of the kinematics and
      spatiotemporal variability of tongue behaviors during swallowing are limited to a
      handful of analyses of data from the X-ray microbeam database. In this article, a
      new technique, electromagnetic midsagittal articulography (EMMA), is introduced
      for the high-resolution description of oral articulatory movements during
      swallowing. Data from 8 healthy, nondysphagic participants are used to illustrate
      the methods used for data collection and analysis. Movement data were collected
      for 3 fleshpoint positions on the tongue (blade, body, dorsum) during sequences
      of repeated discrete water swallows, and were characterized for variables of
      spatiotemporal variability and 4 discrete kinematic parameters (movement
      amplitude, peak velocity, duration, and kinematic stiffness). These data show
      that the movement trajectories measured using EMMA are consistent with
      descriptions from previous X-ray microbeam studies, indicating that EMMA is a
      feasible method for the detailed study of tongue movements during swallowing.

PMID- 15157135
TI  - Is voice amplification for teachers with dysphonia really beneficial?

PMID- 15157137
TI  - Comparison of conversation, freeplay, and story generation as methods of language
      sample elicitation.
AB  - The spontaneous language sample forms an important part of the language
      evaluation protocol (M. Dunn, J. Flax, M. Sliwinski, and D. Aram, 1996; J. L.
      Evans and H. K. Craig, 1992; L. E. Evans and J. Miller, 1999) because of the
      limitations of standardized language tests and their unavailability in certain
      languages, such as Afrikaans. This study examined 3 methods of language
      elicitation, namely conversation (CV), freeplay (FP), and story generation (SG),
      on the following 5 measures to determine which method is best for clinical
      practice: number of utterances, variety of syntactic structures, mean length of
      the utterance (MLU), number of syntactic errors, and proportion of complex
      syntactic utterances as elicited from ten 5-year-old, Afrikaans-speaking boys. FP
      elicited significantly more utterances than did SG but elicited a smaller
      proportion of complex syntactic structures than did CV and SG. Furthermore, SG
      elicited longer utterances than did CV or FP. It is recommended that SG be used
      in clinical practice with 5-year-olds if the clinician wishes to observe maximum
      behavior. Where typical behavior is to be evaluated, the clinician can select a
      language elicitation method that best suits the client's personality and
      communication style, bearing in mind that FP does elicit a larger language
      sample.

PMID- 15157138
TI  - The development of early literacy skills among children with speech difficulties:
      a test of the "critical age hypothesis".
AB  - This article presents a longitudinal study of the early literacy development of
      47 children with speech difficulties from ages 4 to 7 years. Of these children,
      19 with specific speech difficulties were compared with 19 children with speech
      and language difficulties and 19 normally developing controls. The risk of
      literacy difficulties was greater in the group with speech and language
      difficulties, and these children displayed deficits in phoneme awareness at 6
      years. In contrast, the literacy development of children with isolated speech
      problems was not significantly different from that of controls. A path analysis
      relating early speech, language, and literacy skills indicated that preschool
      language ability was a unique predictor of phoneme awareness at 5;8 (years;
      months), which, together with early reading skill, predicted literacy outcome at
      6;9. Once the effects of phoneme awareness were controlled, neither speech
      perception nor speech production processes predicted variation in literacy
      skills. However, it is noteworthy that children with persisting speech
      difficulties at 6;9 were particularly vulnerable to deficits in reading-related
      processes.

PMID- 15157139
TI  - Input that contradicts young children's strategy for mapping novel words affects
      their phonological and semantic interpretation of other novel words.
AB  - Children tend to choose an entity they cannot already label, rather than one they
      can, as the likely referent of a novel noun. The effect of input that contradicts
      this strategy on the interpretation of other novel nouns was investigated. In pre
      and posttests, 4-year-olds were asked to judge whether novel nouns referred to
      "name-similar" familiar objects or novel objects (e.g., whether japple referred
      to an apple or a binder clip). During an intervening treatment phase, they were
      asked to pick the referents of novel nouns from pairs of familiar objects
      (Experiments 1 and 3) or were taught subordinate names for familiar objects
      (Experiment 2). Most resisted the lure of phonological similarity in the pretest
      but increased selection of name-similar familiar objects over novel ones in the
      posttest. In Experiment 3, which involved monosyllables that differed in initial
      phoneme from the familiar words, treatment produced this effect only when
      accompanied by a rhyme-sensitization procedure. Experiment 2 included two other
      age groups: 2-year-olds, who were less resistant to phonological similarity in
      the pretest and responded to the treatment like the 4-year-olds; and adults, who
      nearly always selected the novel objects in the pretest and posttest. For
      children, the impact of treatment was positively associated with ability to
      detect phonological similarity and negatively associated with vocabulary size.

PMID- 15157140
TI  - Semantic features in fast-mapping: performance of preschoolers with specific
      language impairment versus preschoolers with normal language.
AB  - This study examined the receptive language skills of young children (4-6 years
      old) with specific language impairment (SLI). Specifically, the authors looked at
      their ability to fast-map semantic features of objects and actions and compared
      it to the performance of age-matched peers with normally developing language
      (NL). Children completed a computer task during which they were exposed to novel
      objects and actions with novel names. The children then were asked questions
      about the semantic features of these novel objects and actions. Overall, the
      questions about actions were more difficult for children than objects. The
      children with SLI were able to recognize fewer semantic features than were their
      peers with NL. They also performed poorly relative to their peers on a lexical
      label recognition task. These results lend support to the idea that children with
      SLI have broader difficulties with receptive vocabulary than simply a reduced
      ability to acquire labels.

PMID- 15157141
TI  - The interaction between vocabulary size and phonotactic probability effects on
      children's production accuracy and fluency in nonword repetition.
AB  - Adults' performance on a variety of tasks suggests that phonological processing
      of nonwords is grounded in generalizations about sublexical patterns over all
      known words. A small body of research suggests that children's phonological
      acquisition is similarly based on generalizations over the lexicon. To test this
      account, production accuracy and fluency were examined in nonword repetitions by
      104 children and 22 adults. Stimuli were 22 pairs of nonwords, in which one
      nonword contained a low-frequency or unattested two-phoneme sequence and the
      other contained a high-frequency sequence. For a subset of these nonword pairs,
      segment durations were measured. The same sound was produced with a longer
      duration (less fluently) when it appeared in a low-frequency sequence, as
      compared to a high-frequency sequence. Low-frequency sequences were also repeated
      with lower accuracy than high-frequency sequences. Moreover, children with
      smaller vocabularies showed a larger influence of frequency on accuracy than
      children with larger vocabularies. Taken together, these results provide support
      for a model of phonological acquisition in which knowledge of sublexical units
      emerges from generalizations made over lexical items.

PMID- 15157142
TI  - Assessment of phonemic awareness and word reading skills of people with complex
      communication needs.
AB  - A series of phonemic awareness (PA) and single-word reading tasks, which did not
      require spoken responses, was developed for administration to people with complex
      communication needs. The aims of the study were to (a) determine the construct
      validity of the PA tasks and (b) investigate the relationship between PA and
      single-word reading in adults with complex communication needs. Forty adults with
      physical and/or intellectual disability were administered these tasks and a
      standardized measure of receptive spoken vocabulary. In assessing construct
      validity, data from all participants, including those who used speech, were
      included in a factor analysis, which indicated that the PA tasks loaded onto a
      single factor. This factor was interpreted to be PA. The relationship between PA
      and single-word reading in adults with complex communication needs was determined
      using correlational and multiple regression analyses of data from 34 of the
      original participants who did not have functional speech skills. These analyses
      indicated that receptive spoken vocabulary accounted for a significant amount of
      variance on most tasks. Additional significant variance in performance on the
      single-word reading tasks was accounted for by performance on the PA tasks, in
      particular, Nonword Blending and Phoneme Analysis. These results indicate that
      the tasks developed provide a valid means of assessing PA and single-word reading
      skills. In addition, the results indicate that adults with complex communication
      needs demonstrate the same positive association between PA and reading as has
      been found in other groups of individuals with and without disability.

PMID- 15157143
TI  - Grade-related changes in the production of African American English.
AB  - This investigation examined grade as a source of systematic variation in the
      African American English (AAE) produced by students in preschool through fifth
      grades. Participants were 400 typically developing African American boys and
      girls residing in low- or middle-income homes in an urban-fringe community or
      midsize central city in the metropolitan Detroit area. Between preschoolers and
      kindergartners, and between first through fifth graders, there were no
      significant differences in the amounts of dialect produced during a picture
      description language elicitation context. However, there was a significant
      downward shift in dialect production at first grade. Students who evidenced
      dialect shifting outperformed their nonshifting peers on standardized tests of
      reading achievement and vocabulary breadth.

PMID- 15157144
TI  - Taxometric analyses of specific language impairment in 3- and 4-year-old
      children.
AB  - Specific language impairment (SLI), like many diagnostic labels for complex
      behavioral conditions, is often assumed to define a category of children who
      differ not only in degree but also in kind from children developing language
      normally. Although this assumption has important implications for theoretical
      models and clinical approaches, its validity has not been tested. In this study,
      distributions of language scores from children at ages 3 (N = 620) and 4 (N =
      623) years were analyzed using a taxometric procedure known as "mean above minus
      below a cut" (MAMBAC; P. E. Meehl and L. J. Yonce, 1994). Language scores were
      distributed dimensionally at both ages, failing to support the hypothesis of a
      qualitatively distinct group corresponding to children with SLI.

PMID- 15157146
TI  - Vascular zip codes in angiogenesis and metastasis.
AB  - In vivo screening of phage-displayed peptide libraries has revealed extensive
      molecular differences in the blood vessels of individual normal tissues.
      Pathological lesions also put their signature on the vasculature; in tumours,
      both blood and lymphatic vessels differ from normal vessels. The changes that
      characterize tumour blood vessels include selective expression of certain
      integrins. Peptides isolated by in vivo phage display for homing to tumours have
      been shown to be useful in directing therapeutic agents to experimental tumours.
      The targeting can enhance the efficacy of the therapy while reducing side
      effects. Phage screening has also revealed lung-specific vascular markers that
      promote tumour metastasis to the lungs by mediating specific adherence of tumour
      cells to the lung vasculature. These phage-screening studies have revealed a
      previously unsuspected degree of vascular specialization and provide potentially
      useful guidance devices for targeted therapies.

PMID- 15157147
TI  - Structural basis for ligand recognition by RGD (Arg-Gly-Asp)-dependent integrins.
AB  - Since the discovery of the RGD sequence motif as the essential cell attachment
      site in Fn (fibronectin), RGD-dependent ligand recognition by integrins has been
      the major focus of many integrin researches. Although many integrins recognize
      RGD-containing ligands, it is believed that residues outside the RGD motif
      provide specificity as well as high affinity for each integrin-ligand pair. These
      'secondary' sites are generally assumed to interact directly with the alpha
      subunit of integrin, whereas the RGD motif binds primarily to the beta subunit.
      This necessitates that the integrin-ligand interface comprises a relatively
      large, or even scattered, area. Molecular electron microscopy and single-particle
      analysis were performed on a headpiece fragment of integrin alpha5beta1 in the
      presence and absence of bound ligand (Fn fragment), and revealed a marked shape
      change of the beta subunit hybrid and I-like domains that is linked with the
      ligand docking. Furthermore, electron microscopy images revealed a focal rather
      than a large contact area at the alpha5beta1-Fn interface, raising a question
      about '2-site docking model'. Kinetic analysis of real-time binding data showed
      that the synergy site greatly enhances kon but has little effect on the stability
      or koff of the complex, suggesting that the synergy site exerts its positive
      effect on alpha5beta1 binding by facilitating the initial encounter, rather than
      by contributing to the protein-protein interaction surface. Thus the ligand
      recognition mechanism by integrins needs further refinement through more
      structural analyses of the complexes as well as kinetic analysis of binding data.

PMID- 15157148
TI  - Monoclonal antibodies as probes of integrin priming and activation.
AB  - Integrins are a family of heterodimeric, transmembrane receptors that mediate a
      range of cell-cell and cell-extracellular matrix interactions in an array of
      physiological and pathophysiological situations. Integrin-mediated cell adhesion
      is dynamically regulated in vivo to facilitate cell anchorage and movement, but
      prevents aberrant trafficking and aggregation. Following ligand engagement,
      integrin signalling imposes a spatial constraint on the assembly of signalling
      complexes and controls the transduction of mechanical force to the cytoskeleton.
      This transmembrane passage of signals via integrins is achieved both by
      clustering of receptors, which makes the ligand and effector engagement more
      favourable kinetically, and by induction of conformational changes, that
      theoretically creates ligand and effector binding sites de novo. Clustering and
      conformational changes can be triggered both from the inside of the cell
      (resulting in acquisition of ligand-competent conformers) and from the outside
      (ligand-induced signalling). In this paper, these processes will be described and
      distinguished by the terms priming and activation, respectively. Although both
      clustering and conformation are important for integrin function, the latter will
      be the main focus of this article; in particular, the importance of monoclonal
      antibodies for the study of integrin shape changes.

PMID- 15157149
TI  - Structural basis for integrin alphaIIbbeta3 clustering.
AB  - We have expressed two proteins that correspond to the transmembrane and
      cytoplasmic domains of integrin alphaIIb and beta3 subunits. Characterization of
      these proteins, dispersed in anionic and zwitterionic micelles, revealed that,
      rather than interacting with each other, the two proteins associated into
      homodimers and homotrimers respectively. Moreover, studies using the TOXCAT assay
      system confirmed that the alphaIIb and beta3 transmembrane domains can self
      associate in biological cell membranes. Transmembrane domain-mediated homo
      oligomerization provides a plausible structural basis for integrin clustering and
      could promote integrin activation as well. Indeed, replacing specific residues in
      the transmembrane helix of either alphaIIb or beta3 with an asparagine residue
      resulted in a facilitated homo-oligomerization of the mutated transmembrane
      helix, promoted the formation of integrin clusters on the cell surface and
      shifted alphaIIbbeta3 to its activated state. Thus these studies support the
      hypothesis that the transmembrane domains play a vital role in the function and
      regulation of alphaIIbbeta3.

PMID- 15157150
TI  - Hierarchical assembly of cell-matrix adhesion complexes.
AB  - The adhesion of cells to the extracellular matrix is a dynamic process, mediated
      by a series of cell-surface and matrix-associated molecules that interact with
      each other in a spatially and temporally regulated manner. These interactions
      play a major role in tissue formation, cellular migration and the induction of
      adhesion-mediated transmembrane signals. In this paper, we show that the
      formation of matrix adhesions is a hierarchical process, consisting of several
      sequential molecular events. One of the earliest steps in surface recognition is
      mediated, in some cells, by a 1 microm-thick cell-surface hyaluronan coat, which
      precedes the establishment of stable, cytoskeleton-associated adhesions. The
      earliest forms of these integrin-mediated contacts are dot-shaped FXs (focal
      complexes), which are formed under the protrusive lamellipodium of migrating
      cells. These adhesions recruit, sequentially, different anchor proteins that are
      involved in binding the actin cytoskeleton to the membrane. Conspicuous in its
      absence from FXs is zyxin, which is recruited to these sites only on retraction
      of the leading edge and the transformation of the FXs into a focal adhesion.
      Continuing application of force to focal adhesions results in the formation of
      fibrillar adhesions and reorganization of the extracellular matrix. The formation
      of these adhesions depends on actomyosin contractility and matrix pliability.

PMID- 15157151
TI  - Anoikis.
AB  - Anoikis is apoptosis induced by loss of cell adhesion or inappropriate cell
      adhesion. Adhesion on the extracellular matrix is important to determine whether
      a cell is in the correct location and to delete displaced cells by apoptosis. The
      ability to overcome this requirement has important implications for metastatic
      cancer. However, how adhesion signals are interpreted by a cell into a life or
      death decision is complex. In this paper, we will examine this from the point of
      view of the apoptotic machinery of the cell, and discuss the various ways in
      which adhesion can influence this process.

PMID- 15157152
TI  - Lipid rafts: microenvironments for integrin-growth factor interactions in neural
      development.
AB  - The development of a complex multicellular organ such as the nervous system
      requires precise regulation of cell migration, proliferation and survival. This
      regulation in turn requires the integration of long-range signals, such as growth
      factors, with short-range cues that define the precise location and cellular
      neighbours for any given cell. This short review examines one integrative
      mechanism, integrin-growth factor receptor interactions, and explores the role of
      lipid rafts in the molecular mechanisms that underlie the receptor interactions.

PMID- 15157153
TI  - Imaging protein-protein interactions in cell motility using fluorescence
      resonance energy transfer (FRET).
AB  - Protein-protein interactions and signal transduction pathways have traditionally
      been analysed using biochemical techniques or standard microscopy. Although
      invaluable in the delineation of protein hierarchy, these methods do not provide
      information on the true spatial and temporal nature of complex formation within
      the intact cell. Recent advances in microscopy have allowed the development of
      new methods to analyse protein-protein interactions at very high resolution in
      both fixed and live cells. The present paper provides a brief overview of using
      fluorescence resonance energy transfer to analyse directly molecular interactions
      and conformational changes in various proteins involved in the regulation of cell
      adhesion and motility.

PMID- 15157154
TI  - Talin controls integrin activation.
AB  - Tight, dynamic control of the affinity of integrin adhesion receptors for their
      extracellular ligands (integrin activation) is essential for the development and
      functioning of multicellular organisms. Integrin activation is controlled by
      intracellular signals that, through their action on integrin cytoplasmic domains,
      induce conformational changes in integrin extracellular domains, resulting in
      increased affinity for the ligand. Recent results indicate that the binding of
      talin, a major actin-binding protein, to integrin beta tails represents a final
      common step in integrin activation pathways. The major integrin-binding site lies
      within the talin FERM (four-point-one, ezrin, radixin, moesin) domain, and
      binding occurs via a variant of the classical PTB domain (phosphotyrosine-binding
      domain)-NPxY interaction. Formation of this talin-integrin complex plays a
      critical role in integrin activation, since mutations, in either talin or
      integrin beta tails, which disrupt complex formation, inhibit integrin
      activation. Furthermore, use of RNA interference to knockdown talin expression
      selectively reveals that talin is essential for integrin activation in response
      to physiological agonists. Thus the association of the cytoskeletal protein talin
      with integrin beta cytoplasmic domains is a critical step during integrin
      activation, and regulation of this step may be a final common element in the
      signalling pathways that control integrin activation.

PMID- 15157156
TI  - Integrin regulation of cell signalling and motility.
AB  - Integrins clearly play a key role in regulating both mitogenic signalling and
      cell migration. Thus integrins modulate the efficiency of the Erk (extracellular
      signal-regulated kinase)/MAP kinase (mitogen-activated protein kinase) pathway,
      acting at several distinct levels. We have shown that both cAMP-dependent protein
      kinase and PAKs (p21-activated kinases) play a role in integrin regulation of the
      Erk pathway, acting primarily at the level of Raf-1. Integrins and PAKs also play
      a role in the control of cell migration. Thus we have discovered a novel protein
      that links the alpha5beta1 integrin to migration controlled by Rho-family
      GTPases. This protein, termed Nischarin, is a large cytosolic macromolecule that
      is not related to well-known protein families. The N-terminus of Nischarin
      interacts with a short segment of the cytoplasmic domain of the alpha5 integrin
      subunit. Overexpression of Nischarin alters actin organization and inhibits Rac
      driven cell migration and tumour cell invasion. Use of effector domain mutants of
      Rac suggest that Nischarin acts downstream of Rac, probably at the level of PAK
      family kinases. These studies emphasize the intricate connection between
      integrins and Rho-family GTPases and their effectors in controlling both
      mitogenesis and migration.

PMID- 15157155
TI  - Integrin regulation of epidermal growth factor (EGF) receptor and of EGF
      dependent responses.
AB  - Integrin signalling co-ordinates with signalling originating from growth factor
      receptors in the co-operative control of cell proliferation, survival and
      migration. Increasing evidence suggests that integrins form physical complexes at
      the cell membrane with growth factor receptors, giving rise to signalling
      platforms at the adhesive sites. It is probable that at these sites integrins
      regulate adhesion and at the same time physically constrain and direct the
      response to soluble growth factors towards proliferation or survival stimuli.
      These co-operative effects might depend on integrin ability to activate growth
      factor receptors. In the present paper, we summarize our recent study showing
      that integrin-dependent adhesion triggers ligand-independent EGFR (epidermal
      growth factor receptor) activation to transduce downstream signalling. In
      addition, we also show that integrin-induced signalling pathways are necessary
      for EGF-dependent transcriptional response, demonstrating the requirement of the
      co-operation between cell-matrix adhesion and EGFR to achieve full biological
      responses.

PMID- 15157157
TI  - Granulocyte apoptosis: who would work with a 'real' inflammatory cell?
AB  - The neutrophil granulocyte is a key factor in cellular innate defence mechanisms
      against infection or tissue damage. Granulocyte apoptosis is now acknowledged to
      have a critical role in progression of inflammatory responses. Granulocytes are
      preprogrammed to die with important physiological mechanisms for non-inflammatory
      clearance. Shutdown of secretory capacity represents an important aspect of the
      programme of biochemical events that accompany neutrophil apoptosis together with
      surface molecular changes that serve to identify apoptotic cells as targets for
      phagocytic removal. Defining the underlying regulatory mechanisms together with
      the changes in patterns of gene/protein expression associated with granulocyte
      death remains a challenge. Use of novel strategies for inducing cell death will
      allow biochemical approaches to dissect the underlying pathways. Although study
      of granulocyte cell death has especial difficulties when compared with other cell
      types, there are clearly potential benefits for new therapeutic approaches to
      treat inflammatory diseases.

PMID- 15157158
TI  - Getting to grips with the granulocyte: manipulation of granulocyte behaviour and
      apoptosis by protein transduction methods.
AB  - Human granulocytes clearly play an important role in host defence against
      invading organisms, however they have also been implicated in the pathogenesis
      and progression of many chronic inflammatory diseases. In addition, these cells
      have been paramount in gaining a better understanding of many key-signalling
      pathways regulating fundamental biological processes. Since granulocytes are
      terminally differentiated and undergo relatively rapid constitutive apoptosis it
      has been difficult to manipulate intracellular events by transfection or
      transduction procedures. It has been shown in recent years that the HIV-TAT
      protein transduction system can be successfully used in granulocytes to
      manipulate key signalling mechanisms regulating functional responsiveness and
      survival. In this paper, we review recent literature highlighting important
      developments using this system in isolated human granulocytes and in inflammatory
      process in vivo where these cells play a prominent role.

PMID- 15157159
TI  - Characterization of the survival effect of tumour necrosis factor-alpha in human
      neutrophils.
AB  - Granulocyte apoptosis has been proposed as a fundamental, injury-limiting
      granulocyte-clearance mechanism. As such, inhibition of this process may prevent
      the resolution of inflammation. Our previous studies have shown that TNFalpha
      (tumour necrosis factor-alpha) has a bi-modal influence on the rate of
      constitutive neutrophil apoptosis in vitro, causing early acceleration and late
      inhibition of this process. The pro-apoptotic effect is uniquely TNFR1 (TNF
      receptor 1) and TNFR2-dependent and the latter survival process is mediated via
      phosphoinositide 3-kinase and NF-kappaB (nuclear factor-kappaB) activation. In
      the present study, we show that, in contrast with GM-CSF (granulocyte/macrophage
      colony-stimulating factor), the delayed addition (i.e. at 6 h) of TNFalpha
      increases its survival effect despite substantial loss of neutrophil TNFR1 and
      TNFR2 at that time. This paradox was resolved using PBMC (peripheral blood
      mononuclear cell)-deplete and 5% PBMC-replete neutrophil cultures, where the
      enhanced survival effect observed after delayed TNFalpha addition was shown to be
      PBMC-dependent. TNFR2-blocking antibodies had no effect on the late survival
      effect of TNFalpha, implying a TNFR1-dependent process. Finally, I-kappaBalpha
      (inhibitory kappaB-alpha) and NF-kappaB time-course studies demonstrated that the
      survival effects of both GM-CSF and TNFalpha could be explained by maintenance of
      functional NF-kappaB.

PMID- 15157160
TI  - Early events in spontaneous neutrophil apoptosis.
AB  - Neutrophils are very abundant, short-lived leucocytes and their death by
      apoptosis is central to homoeostasis and the resolution of inflammation, yet the
      trigger for apoptosis is still a topic of debate. Depolarization of the
      mitochondrial membrane has been supposed to initiate neutrophil spontaneous
      apoptosis, as neutrophils gradually lose the anti-apoptotic protein Mcl-1 and Bax
      translocates and inserts into the mitochondrial membrane. However, other reports
      show that caspase 8 is required for neutrophil apoptosis, suggesting the
      involvement of DR (death receptor) signalling. As DR ligation is not required for
      neutrophil apoptosis, this raises the intriguing possibility that activation of
      caspase 8 during neutrophil apoptosis occurs via a novel mechanism. In the
      present paper, we discuss the current evidence for mechanisms occurring in
      neutrophil apoptosis, which could trigger DR signalling in the absence of DR
      ligation.

PMID- 15157161
TI  - Regulation of granulocyte apoptosis by NF-kappaB.
AB  - Granulocyte apoptosis is a crucial part of the successful resolution of
      inflammation. In vitro results show that activation of NF-kappaB (nuclear factor
      kappaB) in granulocytes is a survival mechanism. NF-kappaB inhibitors increase
      the rate of constitutive apoptosis in neutrophils and eosinophils and cause these
      cells to respond to the pro-apoptotic effects of TNF-alpha (tumour necrosis
      factor-alpha). Results from both in vivo and in vitro experiments suggest that
      there are at least two important waves of NF-kappaB activation in inflammatory
      loci, which increase the expression of COX-2 (cyclooxygenase-2), itself an NF
      kappaB controlled gene. The first wave causes the production of inflammatory
      mediators such as PGE2 (prostaglandin E2), allowing the establishment of
      inflammation. The second wave causes the synthesis of PGD2 and its metabolites
      that induce granulocyte apoptosis by inhibiting NF-kappaB activation. These
      metabolites may therefore be important physiological mediators controlling the
      resolution of inflammation. Although NF-kappaB is an important target for anti
      inflammatory therapy, the timing of inhibition in vivo may be crucial, to ensure
      that production of PGD2 and its sequential metabolites can occur.

PMID- 15157162
TI  - What can we learn from highly purified neutrophils?
AB  - Neutrophil purification has traditionally been performed by centrifugation of
      leucocytes through density gradients. These reliable methods produce populations
      that are typically >95% pure neutrophils, and have allowed the widespread study
      of the function of these cells. Our recent work has suggested that residual
      monocytes may play a more important role than has been previously realized, and
      suggest that for some functional experiments, further purification of cells is
      required to understand fully the neutrophil phenotype.

PMID- 15157163
TI  - Gene profiling of in vitro and in vivo models of delayed neutrophil apoptosis: a
      common pathway?
AB  - Mechanisms responsible for the termination of an inflammatory response include
      the activation of a genetic programme of cellular suicide termed apoptosis, which
      leads to the elimination of the cellular effectors of acute inflammation,
      particularly the neutrophil. However, delays in this response result in the
      persistence of inflammation and the development of inflammatory disorders.
      Understanding the mechanism that inhibits the process of cell death may be
      helpful in the treatment of inflammatory disorders. Inflammatory cytokines have
      been shown to inhibit apoptosis through stabilization of the mitochondria and
      inhibition of the caspase cascade. To date, how these processes are inhibited
      remains the central question. We hypothesize that the decision for the delay in
      neutrophil apoptosis is made through signals delivered on the cell surface, which
      activate combinations of specific genes that inhibit the cell death pathway. Gene
      chip microarray experiments were performed in in vivo and in vitro models of
      delayed neutrophil apoptosis. Analysis has yielded changes in a large number of
      genes involved in inflammation, metabolism, signalling, mitochondrial function
      and apoptosis. A number of genes have been identified as suitable targets
      responsible for the regulation of neutrophil apoptosis and their expression was
      confirmed by real-time PCR and explored at the level of the protein. Their
      functional role in the apoptotic response is now being determined. One
      significant finding is that the gene patterns of delay in vitro and in vivo
      appear to be different, indicating the possibility for different pathways
      regulating the delay in neutrophil apoptosis.

PMID- 15157164
TI  - An apoptosis differentiation programme in human polymorphonuclear leucocytes.
AB  - Human PMNs (polymorphonuclear leucocytes or neutrophils) are essential to the
      innate immune response against bacterial pathogens and are a key part of the
      acute inflammatory response. Although progress has been made, the molecular basis
      for termination of inflammation during bacterial infection in humans is largely
      undefined. To that end, we used genomics strategies to gain new insight into
      processes that facilitate resolution of neutrophil-mediated inflammation and
      bacterial infection. On the basis of a series of recent studies, we propose that
      global changes in PMN gene expression after phagocytosis comprise an apoptosis
      differentiation programme, which represents the final stage of transcription
      regulated PMN maturation. Our studies indicate that the apoptosis differentiation
      programme regulates multiple post-phagocytic processes in human neutrophils, such
      as cell fate and proinflammatory activity, and is modulated by PMN-derived
      reactive oxygen species. Collectively, these studies establish a global model of
      host cell-pathogen interaction, which provides fundamental insight into the
      resolution of infection in humans.

PMID- 15157165
TI  - Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane
      blebbing and vesicle release, CD43 and CD16 down-regulation and
      phosphatidylserine externalization.
AB  - CD43 down-regulation during the apoptosis of PMN (polymorphonuclear cells) is not
      caused by proteolysis or internalization. Could it be released with bleb-derived
      membrane vesicles? Membrane blebbing was followed by microscopy on PMN
      'synchronized' by an overnight incubation at 15 degrees C before their
      spontaneous apoptosis at 37 degrees C. Released vesicles were quantified by flow
      cytometry. Membrane blebbing, release of bleb-derived membrane vesicles, decrease
      of CD43/CD16 expression and phosphatidylserine externalization occurred
      simultaneously. However, caspase and PKC inhibition prevented annexin binding but
      not blebbing, vesicle release or CD43 expression decrease; myosin light chain
      kinase inhibition prevented cell blebbing and vesicle release but had no effect
      on CD43/CD16 down-regulation or annexin V binding. By electron microscopy, CD43
      appeared poorly expressed on membrane blebs and concentrated at bleb 'necks'. In
      conclusion, CD43 down-regulation is not caused by cell blebbing. Cell blebbing,
      phospholipid 'flip-flop' and CD43/CD16 down-regulation are independent membrane
      events.

PMID- 15157166
TI  - Regulation of granulocyte apoptosis by phosphatidylinositol 3-kinase.
AB  - Granulocytes are critical components of the innate immune system whose lifespan
      is limited by an intrinsic, constitutive, apoptotic pathway. However, the
      lifespan of these cells can be extended at an inflammatory locus through
      interaction with survival factors. Although a wide variety of factors can
      modulate granulocyte survival, they often utilize a common subset of
      intracellular signal transduction pathways. Over the last decade, evidence has
      accumulated that the PI3K (phosphatidylinositol 3-kinase) family of lipid kinases
      may be critical in regulating the ability of granulocytes to survive at
      inflammatory loci. Studies utilizing both pharmacological inhibitors of PI3K and
      isoform-specific knockout mice have demonstrated that this enzyme is needed for
      the anti-apoptotic effects of granulocyte survival factors. More recently, a
      serine/threonine protein kinase, termed protein kinase B (also known as c-akt),
      has been demonstrated to be important in modulating the prosurvival effects of
      PI3K activation. This can occur through modulation of the expression or
      phosphorylation of members of the Bcl-2 (B-cell lymphocytic-leukaemia proto
      oncogene 2) family of apoptosis regulators. This review summarizes recent results
      that have implicated a role for PI3K in regulating granulocyte survival.

PMID- 15157167
TI  - Mammalian Sterile20-like kinase 1 and the regulation of apoptosis.
AB  - Mammalian Sterile20-like kinase 1 (Mst1) is a ubiquitously expressed
      serine/threonine kinase which represents a member of the rapidly expanding family
      of enzymes related to the yeast Sterile20 kinase. Although the physiological
      function of Mst1 and its role in intracellular signalling is still unclear,
      reports to date suggest that Mst1, similar to its yeast homologue, operates in
      the MAPK (mitogen-activated protein kinase) pathway and, in this capacity, may
      represent a putative MAPK kinase kinase kinase. Moreover, there is abundant
      evidence for a role of this enzyme in apoptosis, where not only is it a target
      for caspases, but may also serve as an activator of these proteases to amplify
      the apoptotic signalling pathway. This paper reviews the investigations that have
      led to our current understanding of the mechanisms by which Mst1 may be activated
      and thereby contribute to apoptosis.

PMID- 15157168
TI  - Regulation of neutrophil apoptosis by Mcl-1.
AB  - Neutrophils rapidly undergo spontaneous apoptosis, but this process can be
      considerably delayed by exposure to a variety of agents such as pro-inflammatory
      cytokines. The anti-apoptotic protein of the Bcl-2 family, Mcl-1, plays a key
      role in the regulation of neutrophil apoptosis. The protein has some unusual
      properties compared with other family members, including an extremely high
      turnover rate. Many factors, such as cytokines and local oxygen concentrations,
      can regulate cellular levels of Mcl-1 via transcription and post-transcriptional
      modification, control the survival time of neutrophils within tissues and thereby
      influence the inflammatory response.

PMID- 15157169
TI  - Mitochondria in apoptosis: past, present and future.
AB  - The role of mitochondria in cell death has been increasingly appreciated in the
      last few years and is now well established in a variety of cellular systems. At
      present we know that the involvement of mitochondria is regulated by proteins of
      the Bcl-2 (B-cell lymphocytic-leukaemia proto-oncogene 2) family, which
      biochemically act by altering the properties of mitochondrial membranes to
      facilitate the release of apoptogenic proteins like cytochrome c and Smac/Diablo
      that, once released into the cytosol, are crucial for activating the caspase
      cascade of cell degradation. The precise mechanism of the pro-apoptotic action is
      not fully understood yet, but could be clarified in the near future. Instrumental
      to this clarification is the emerging evidence that CL (cardiolipin), an unusual
      membrane lipid that is predominantly present in mitochondria, is required for the
      action of major pro-apoptotic proteins like Bid and Bax. New results obtained in
      myeloid cells further sustain this possibility and suggest that Bid may be
      involved in the metabolic cycle of CL re-modelling. In agreement with this
      postulate, preliminary results indicate a down-regulation of Bid in parallel to
      the genetic deficiency in CL re-modelling that is associated with a rare human
      disease, 'Barth Syndrome'. Intriguingly, this disease is characterized by
      neutropenia, suggesting a link between myeloid differentiation and cell death
      (and myeloid lymphoma pathogenesis too). I will project current results and
      trends towards future investigations on the involvement of CL and mitochondrial
      membranes in myeloid differentiation, cell death and disease.

PMID- 15157170
TI  - Macrophage apoptosis in host immunity to mycobacterial infections.
AB  - Macrophage apoptosis occurs within the granuloma, which is essential for
      successful immunity to tuberculosis. In vitro macrophage apoptosis is associated
      with the killing of intracellular Mycobacterium tuberculosis. A greater
      understanding of these observations will lead to new immunotherapies and improved
      vaccine design. The relevant apoptotic stimuli, the anti-mycobacterial mechanisms
      that they stimulate and their physiological relevance are reviewed in this paper.

PMID- 15157171
TI  - The role of oxidants and vitamin C on neutrophil apoptosis and clearance.
AB  - We have investigated the role of neutrophil oxidants in the surface changes that
      result in recognition and uptake of neutrophils by macrophages. We have shown
      that H2O2 produced by stimulated neutrophils is essential for the surface
      expression of phosphatidylserine. This does not occur in neutrophils from mice
      with chronic granulomatous disease and may explain the formation of granuloma in
      this condition. We have also investigated the role of intracellular vitamin C on
      neutrophil apoptosis. Cells from vitamin C-deficient mice were found to be less
      likely to undergo both spontaneous and oxidant-induced apoptosis, with eventual
      necrosis being the most probable outcome.

PMID- 15157172
TI  - The importance of resolution of inflammation in the pathogenesis of ANCA
      associated vasculitis.
AB  - The primary small-vessel systemic vasculitides are disorders that target small
      blood vessels, inducing vessel wall inflammation, and are associated with the
      development of anti-neutrophil cytoplasmic antibodies. Multiple organs are
      attacked, including the lungs and kidneys. Increasing knowledge of pathogenesis
      suggests that the antibodies activate neutrophils inappropriately, leading to
      endothelial and vascular damage. Cytokines, such as tumour necrosis factor, can
      facilitate damage by priming the neutrophils and activating endothelial cells.
      Apoptosis of infiltrating neutrophils is also disrupted by anti-neutrophil
      cytoplasmic antibody activation, and removal of these effete cells occurs in a
      pro-inflammatory manner, promoting persistent inflammation. The autoimmune
      response may be promoted by aberrant phagocytosis of apoptotic neutrophils by
      dendritic cells. Understanding the pathogenesis can help to rationalize existing
      therapies and indicate new approaches to therapy.

PMID- 15157173
TI  - Annexin 1 and neutrophil apoptosis.
AB  - ANXA1 (annexin 1), a member of the 'annexin' family of calcium- and phospholipid
      binding proteins, was originally identified as an endogenous mediator of the anti
      inflammatory actions of glucocorticoids. However, this protein exerts multiple
      inhibitory effects on the host inflammatory response, including a preferential
      regulation of the adhesion step of blood-borne neutrophil within the
      microenvironment of an inflamed vasculature. It is now emerging that ANXA1 is
      endowed with other roles, since the protein is abundant in inflammatory exudates
      as it is produced and released by the extravasated neutrophil. In the present
      paper, we review the novel proapoptotic effect of ANXA1 and discuss its potential
      with respect to the pathophysiology of inflammation and leucocyte recruitment.

PMID- 15157174
TI  - Advances in two-dimensional gel matching technology.
AB  - For many years, two-dimensional gel electrophoresis has been the method of choice
      for the investigation of complex mixtures of proteins. Although there are a
      number of emerging technologies that can be applied to proteomics, none can yet
      yield routinely the breadth of information available from two-dimensional gels.
      To be able to obtain instant information regarding molecular mass and pI, as well
      as to highlight quickly the expression changes or unique proteins across a gel
      series requires sophisticated and powerful image analysis software. The range of
      software products offered by Nonlinear Dynamics covers all levels of user
      application and throughput, from the user-guided Phoretix two-dimensional
      approach, when working with a small number of gels, to the automatic processing
      of large numbers of gels with minimal user intervention with Progenesis.
      Integration of the analysis software with powerful database components allows
      advanced gel comparisons and data mining to be performed with statistical
      verification of the results. Spot pick lists can be quickly created and
      automatically linked to a number of commercially available spot picking robots
      further increasing the support for proteomics research. The importance of image
      analysis for accurate, reliable and meaningful results will be discussed. Recent
      advances in development, with particular attention placed on the impact of noise
      contamination within gels, are illustrated and how the Progenesis product from
      Nonlinear Dynamics can be utilized to get the most from two-dimensional gel
      electrophoresis is shown.

PMID- 15157175
TI  - Aspects of the barley seed proteome during development and germination.
AB  - Analysis of the water-soluble barley seed proteome has led to the identification
      of proteins by MS in the major spots on two-dimensional gels covering the pI
      ranges 4-7 and 6-11. This provides the basis for in-depth studies of proteome
      changes during seed development and germination, tissue-specific proteomes,
      cultivar differences related to quality parameters, analysis of the genetic basis
      for spot variations and targeted investigations of specific proteins.

PMID- 15157177
TI  - Proteomic analysis of the Arabidopsis cell wall reveals unexpected proteins with
      new cellular locations.
AB  - We initiated a proteomic study as part of a programme aimed at discovering novel
      functions of the plant cell wall. Cell-wall fragments isolated from cell
      suspension cultures of Arabidopsis thaliana were stripped of protein sequentially
      using CaCl2 and a urea-based buffer. The protein fractions were separated by two
      dimensional gel electrophoresis and individual proteins were identified by MS. We
      identified a number of proteins considered to be resident in other organelles but
      not the cell wall on the basis of their classical biological function. These
      included citrate synthase, which is known to be targeted to mitochondria,
      peroxisomes and glyoxysomes, and luminal binding protein, which is an ER
      (endoplasmic reticulum)-resident protein. Searches of the Arabidopsis database
      revealed that there are several genes encoding putative citrate synthase and
      luminal binding protein. We have also performed detailed analyses of the protein
      sequences and this paper shows how each one contains encrypted targeting
      information that results in the export of the protein to the extracellular
      matrix. We discuss the presence of alternative non-classical secretory pathways
      in plants.

PMID- 15157176
TI  - The use of isotope-coded affinity tags (ICAT) to study organelle proteomes in
      Arabidopsis thaliana.
AB  - Organelle proteomics is the analysis of the protein contents of a subcellular
      compartment. Proteins identified in subcellular proteomic studies can only be
      assigned to an organelle if there are no contaminants present in the sample
      preparation. As a result, the majority of plant organelle proteomic studies have
      focused on the chloroplast and mitochondria, which can be isolated relatively
      easily. However, the isolation of components of the endomembrane system is far
      more difficult due to their similar sizes and densities. For this reason,
      quantitative proteomics methods are being developed to enable the assignment of
      proteins to a specific component of the endomembrane system without the need to
      obtain pure organelles.

PMID- 15157178
TI  - The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor
      structure on function.
AB  - The Cys-loop receptors constitute an important superfamily of LGICs (ligand-gated
      ion channels) comprising receptors for acetylcholine, 5-HT3 (5-hydroxytryptamine;
      5-HT3 receptors), glycine and GABA (gamma-aminobutyric acid; GABAA receptors). A
      vast knowledge of the structure of the Cys-loop superfamily and its impact on
      channel function have been accrued over the last few years, leading to exciting
      new proposals on how ion channels open and close in response to agonist binding.
      Channel opening is initiated by the extracellular association of agonists to
      discrete binding pockets, leading to dramatic conformational changes, culminating
      in the opening of a central ion pore. The importance of channel structure is
      exemplified in the allosteric modulation of channel function by the binding of
      other molecules to distinct sites on the channel, which exerts an additional
      level of control on their function. The subsequent conformational changes
      (gating) lead to channel opening and ion transport. Following channel pore
      opening, ion selectivity is determined by receptor structure in, and around, the
      ion pore. As a final level of control, cytoplasmic determinants control the
      magnitude (conductance) of ion flow into the cell. Thus the Cys-loop receptors
      are complex molecular motors, with moving parts, which can transduce
      extracellular signals across the plasma membrane. Once the full mechanical
      motions involved are understood, it may be possible to design sophisticated
      therapeutic agents to modulate their activity, or at least be able to throw a
      molecular spanner into the works!

PMID- 15157179
TI  - The transmembrane domain of the 5-HT3 receptor: its role in selectivity and
      gating.
AB  - The 5-HT3 (5-hydroxytryptamine) receptor is a typical member of the Cys-loop
      family of ligand-gated ion channels. No atomic resolution structures of these
      proteins have yet been published, and thus structure-function relationships in
      this family of proteins have been largely determined from experimental evidence
      combined with the use of homologous proteins and lower resolution images. Here,
      recent advances in our knowledge of the structure and function of the
      transmembranous part of the 5-HT3 receptor are reviewed. These show that the pore
      region, M2, is largely alpha-helical, and ion selectivity may be controlled by
      charged amino acid rings at each end of this pore region. The mechanism by which
      the pore opens is probably similar to that proposed for the nACh receptor, i.e. a
      twist of M2, caused by rotation in the extracellular domains, removes hydrophobic
      residues from the ion path.

PMID- 15157180
TI  - Structural elements involved in activation of the gamma-aminobutyric acid type A
      (GABAA) receptor.
AB  - Ligand-gated ion channels function as rapid signal transducers, converting
      chemical signals (in the form of neurotransmitters) into electrical signals in
      the postsynaptic neuron. This is achieved by the recognition of neurotransmitter
      at its specific-binding sites, which then triggers the opening of an ion channel
      ('gating'). For this to occur rapidly (< 1 ms), there must be an efficient
      coupling between the agonist-binding site and the gate, located more than 30
      angstroms (1 angstroms = 0.1 nm) away. Whereas a great deal of progress has been
      made in elucidating the structure and function of both the agonist-binding site
      and the ion permeation pathway in ligand-gated ion channels, our knowledge of the
      coupling mechanism between these domains has been limited. In this review, we
      summarize recent studies of the agonist-binding site and the ion channel in the
      gamma-aminobutyric acid type A receptor, and discuss those structural elements
      that may mediate coupling between them. We will also consider some possible
      molecular mechanisms of receptor activation.

PMID- 15157181
TI  - The 5-hydroxytryptamine type 3 (5-HT3) receptor reveals a novel determinant of
      single-channel conductance.
AB  - 5-HT3 (5-hydroxytryptamine type 3) receptors are cation-selective ion channels of
      the Cys-loop transmitter-gated ion channel superfamily. Two 5-HT3 receptor
      subunits, 5-HT3A and 5-HT3B, have been characterized in detail, although
      additional putative 5-HT3 subunit genes (HTR3C, HTR3D and HTR3E) have recently
      been reported. 5-HT3 receptors function as homopentameric assemblies of the 5-HT3
      subunit, or heteropentamers of 5-HT3A and 5-HT3B subunits of unknown
      stoichiometry. The single-channel conductances of human recombinant homomeric and
      heteromeric 5-HT3 receptors are markedly different, being <1 and approx. 16 pS
      respectively. Paradoxically, from the results of studies performed on the closely
      related nicotinic acetylcholine receptor, the channel-lining M2 domain of the 5
      HT3A subunit is predicted to enhance cation conduction, whereas that of the 5
      HT3B subunit would not. The present study describes a novel determinant of single
      channel conductance, out with the M2 domain, which accounts for this anomaly.
      Utilizing a panel of chimaeric 5-HT3A and 5-HT3B subunits, a profound determinant
      of single-channel conductance was traced to a putative amphipathic helix (the 'HA
      stretch') within the large cytoplasmic loop of the receptor. Replacement of three
      arginine residues (R432, R436 and R440) unique to the HA stretch of the 5-HT3A
      subunit with the aligned residues (Q395, D399 and A403) of the 5-HT3B subunit
      increased the single-channel conductance 28-fold. Significantly, from
      ultrastructural studies of the Torpedo nicotinic acetylcholine receptor, the key
      residues may be components of narrow openings within the inner vestibule of the
      channel, located in the cytoplasm, which contribute to the permeation pathway.
      Our findings indicate an important and hitherto unappreciated function for the HA
      stretch in the Cys-loop family of transmitter-gated ion channels.

PMID- 15157182
TI  - Differentiating the role of gamma-aminobutyric acid type A (GABAA) receptor
      subtypes.
AB  - The inhibitory tone maintained throughout the central nervous system relies
      predominantly on the activity of neuronal GABAA (gamma-aminobutyric acid type A)
      receptors. This receptor family comprises various subtypes that have unique
      regional distributions, but little is known about the role played by each
      subtype. The majority of the receptors contain a gamma2 subunit and are sensitive
      to modulation by BZs (benzodiazepines), but differ with regard to alpha and beta
      subunits. Mutagenesis studies combined with molecular modelling have enabled a
      greater understanding of receptor structure and dynamics. This can now be
      extended to in vivo activity through translation to genetically modified mice
      containing these mutations. Ideally, the mutation should leave normal receptor
      function intact, and this is the case with mutations affecting the BZ-binding
      site of the GABAA receptor. We have generated mutations, which affect the BZ site
      of different alpha subunits, to enable discrimination of the various behavioural
      consequences of BZ drug action. This has aided our understanding of the roles
      played by individual GABAA receptor subtypes in particular behaviours. We have
      also used this technique to explore the role of different beta subunits in
      conferring the anaesthetic activity of etomidate. This technique together with
      the development of subtype-selective compounds facilitates our understanding of
      the roles played by each receptor subtype.

PMID- 15157183
TI  - Tumour cell growth in culture: dependence on arginine.
AB  - The amino acid arginine has been shown to affect the growth of several tumours,
      although the mechanisms of its action are not clear. In the present study, using
      a human breast tumour cell line (MCF-7), we investigated the arginine
      requirements of tumour cells for optimal protein synthesis and growth, and the
      metabolic pathway responsible for the arginine-dependent growth. The results
      showed that MCF-7 cells are highly dependent on arginine for growth and that the
      requirement for arginine is much higher than for an indispensable amino acid,
      leucine, indicating that arginine is needed for pathways other than protein
      synthesis. In arginine-free cultures, growth could be completely restored by the
      urea cycle intermediate citrulline. However, arginine could not be replaced by
      the urea cycle intermediate and the direct precursor for polyamine synthesis,
      ornithine, or by the polyamine putrescine, suggesting that the high dependence on
      arginine is not due to a requirement for polyamine synthesis. Moreover,
      inhibition of NOS [NO (nitric oxide) synthase] did not affect cell protein
      synthesis and growth, and the arginine analogue and substrate for NOS,
      homoarginine, could not replace arginine, implying that the conversion of
      arginine into NO is not involved in the growth-promoting effects of arginine. The
      major determinant for the high dependence of MCF-7 cells for arginine was found
      to be the irreversible conversion of this amino acid into ornithine by the
      intracellular enzyme arginase. The conversion into ornithine caused a progressive
      depletion of arginine from the culture medium, which ultimately inhibited cell
      protein synthesis and halted growth. Intracellular arginase activity may be the
      major factor determining the requirement for arginine of all cells in culture.

PMID- 15157184
TI  - Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome.
AB  - Idiopathic NS (nephrotic syndrome) is characterized by massive proteinuria, due
      to a leak in the glomerular barrier to proteins. Genetic defects that affect the
      function and the composition of the glomerular capillary wall, in particular of
      the visceral epithelial cells, have recently been recognized as the cause of
      familial forms of NS. MCNS (minimal change NS) and FSGS (focal and segmental
      glomerulosclerosis) are common non-familial forms of NS in which the causative
      defect has not yet been identified. Several studies have shown that non-familial
      NS is associated with the presence of circulating permeability factors and with
      complex disturbances in the immune system. Thus far, there is no direct evidence
      that these factors directly alter glomerular permeability to proteins, and some
      of these factors may be a consequence, rather than a cause, of NS. In this
      review, we will briefly highlight the mechanisms that underlie proteinuria in
      general and focus on the immunological disturbances associated with idiopathic
      NS, with attention to potential mechanisms whereby the immune system may directly
      act on the glomerular capillary filter.

PMID- 15157185
TI  - Effect of esmolol on positive-pressure ventilation-induced variations of arterial
      pressure in anaesthetized humans.
AB  - Positive-pressure ventilation-induced variations in arterial pressure have been
      related to cardiac sympathetic activity in animals. However, the effect of beta
      adrenoceptor blockade on these variations in anaesthetized humans under positive
      pressure ventilation has not yet been investigated. In the present study, RAPV
      (respiratory-related arterial pressure variability) and %SPV (percentile systolic
      pressure variation) were determined before and after esmolol treatment in ten
      mechanically ventilated patients. RAPV and %SPV decreased significantly after
      intravenous esmolol (1 mg/kg of body weight) treatment (maximal decrease of RAPV,
      50% and %SPV, 35%). Linear regression analysis of RAPV and %SPV before and after
      esmolol treatment both revealed high correlation (r = 0.93 and 0.91
      respectively). The amplitudes of RAPV and %SPV also significantly increased in a
      graded way with higher tidal volumes. Thus we propose that esmolol suppresses the
      variations in arterial pressure induced by positive-pressure mechanical
      ventilation, and we suggest that RAPV and %SPV may be alternative choices for
      monitoring cardiac sympathetic regulation in anaesthetized patients under
      positive-pressure ventilation.

PMID- 15157188
TI  - Transmission electron microscopy of fluorapatite-gelatine composite particles
      prepared using focused ion beam milling.
AB  - In this paper, synthetic fluorapatite-gelatine composite particles are prepared
      for transmission electron microscopy (TEM) studies using two methods based on
      focused ion beam (FIB) milling. TEM studies on the FIB-prepared specimens are
      compared with TEM observations on samples prepared using an ultramicrotome. The
      results show that ultramicrotome slicing causes significant cracking of the
      apatite, whereas the ion beam can be used to make high-quality, crack-free
      specimens with no apparent ion beam-induced damage. The TEM observations on the
      FIB-prepared samples confirm that the fluorapatite composite particles are
      composed of elongated, preferentially orientated grains and reveal that the grain
      boundaries contain many small interstices filled with an amorphous phase.

PMID- 15157186
TI  - Trypanothione reductase from the human parasite Entamoeba histolytica: a new drug
      target.
AB  - Although there is a general agreement that the protist Entamoeba histolytica
      lacks glutathione, it has been a matter of dispute as to whether this human
      parasite contains the glutathione derivative known as trypanothione. In the
      present study, we describe a gene for the TR (trypanothione reductase) obtained
      from E. histolytica by PCR amplification of its DNA. After Northern-blot
      analysis, the radiolabelled DNA probe from Trypanosoma cruzi hybridizes with the
      total RNA of Entamoeba, showing that the TR gene is expressed as mRNA. We have
      demonstrated the presence of the NADPH-dependent TR activity in vitro with
      partially purified extracts and showed also that the thiol-bimane compound
      isolated and purified from E. histolytica trophozoites, unequivocally
      corresponds, by matrix-assisted laser-desorption ionization-time-of-flight MS, to
      the characteristic monoprotonated ion of trypanothione-(bimane)(2) with m/z
      1104.4 and the trypanothione-(bimane) with m/z 914.3. The PCR product consisted
      of 1476 bp (491 deduced amino acids), has sequences diagnostic for the reducing
      catalytic site (CVNVGC) as well as domains for binding NADPH, FAD I and FAD II
      that are present in all members of this group of disulphide-reducing enzymes, as
      well as those unique to TRs. The putative protein sequence is 86% identical with
      that of TR from T. cruzi and it is also clearly distinguishable from other
      related reductases by phylogenetic analysis. We can conclude, from these highly
      reliable experiments, that E. histolytica contains the TR enzyme and the thiol
      compound trypanothione that was previously supposed to occur only in
      trypanosomatids.

PMID- 15157189
TI  - FIB-induced damage in silicon.
AB  - The damage created in silicon transmission electron microscope specimens prepared
      using a focused ion beam miller is assessed using cross-sections of trenches
      milled under different beam conditions. Side-wall damage consists of an amorphous
      layer formed by direct interaction with the energetic gallium ion beam; a small
      amount of implanted gallium is also detected. By contrast, bottom-wall damage
      layers are more complex and contain both amorphous films and crystalline regions
      that are richer in implanted gallium. More complex milling sequences show that
      redeposition of milled material, enriched in gallium, can occur depending on the
      geometry of the mill employed. The thickness of the damage layers depends
      strongly on beam energy, but is independent of beam current. Monte Carlo
      modelling of the damage formed indicates that recoil silicon atoms contribute
      significantly to the damaged formed in the specimen.

PMID- 15157190
TI  - Using the FIB to characterize nanoparticle materials.
AB  - In the 1-100-nm size regime, the properties of materials can differ significantly
      from those of their bulk counterparts. The present study applies the focused ion
      beam (FIB) tool to the characterization of nanoscale structures for scanning and
      transmission electron microscopy. The strength of this method is its ability to
      manufacture samples that cannot be produced using traditional means. The films of
      nanoparticles examined here are examples of such systems; the films are found to
      be not fully dense, composed of chemically heterogeneous areas and mechanically
      different from the substrate. Distinct advantages of the application of the FIB
      for characterization of nanoscale structures are highlighted for several
      nanoparticle structures. This successful application of FIB techniques provides a
      pathway to integrate the study of nanoscale production techniques and their
      resulting structure-property relationships.

PMID- 15157191
TI  - Application of the dual-beam FIB/SEM to metals research.
AB  - The dual-beam microscope is a combination of a focused ion beam with an electron
      beam. The instrument used in this work is also equipped with an energy-dispersive
      X-ray system for local elemental analysis. This powerful tool gives access to
      specific features inside a material. Two different applications are presented in
      this paper: (1) cross-sections and transmission electron microscope specimens cut
      in order to investigate the interface between an aluminium substrate and its
      epoxy coating; and (2) a grain boundary in a Cu(3)Au alloy. In both cases, the
      dual beam succeeded where other methods failed.

PMID- 15157192
TI  - Circuit editing of copper and low-k dielectrics in nanotechnology devices.
AB  - Circuit editing of integrated circuit (IC) devices fabricated in 100-nm and
      smaller technologies has moved IC microsurgery into nanosurgery. Although the
      dimensions are challenging, an additional challenge is to mill the dielectric
      materials that are employed controllably. There are interesting biological
      similarities as carbon content and porosity increase in order to minimize the
      dielectric constant. These porous organic materials are extremely delicate and
      are readily carbonized under the ion beam. Besides minimizing carbonization, the
      etching of these materials must be minimized during the removal of a metallized
      area. A further challenge has been caused by the continuing tightening of
      fabrication specifications; the dielectric materials are dispersed (although not
      randomly) within the metallizations in order to reduce variations during a
      planarization process. In addition, to improve planarization tolerances, dummy
      metallizations are placed in regions where the need is only mechanical and not
      electrical. Neither of these 'extra' structures is readily available to assist in
      edit planning. To address these dielectrics and the structures in which they are
      found, several techniques--including chemistries--have been developed. Methods to
      increase the etching of metallization relative to the dielectric are reviewed,
      including chemistries that improve the selectivity of copper to dielectric.

PMID- 15157193
TI  - Thermal stability of Ti and Pt nanowires manufactured by Ga+ focused ion beam.
AB  - Ti and Pt nanowires have been produced by ultra high-vacuum molecular beam
      epitaxy deposition of Ti thin films and focused ion beam (FIB) deposition of Pt
      thin films, followed by cross-sectional FIB sputtering to form electron
      transparent nanowires. The thermal stability of the nanowires has been
      investigated by in situ thermal cycling in a transmission electron microscope.
      Epitaxial single crystal Ti nanowires on (0001)Al(2)O(3) substrates are
      microstructurally stable up to 550-600 degrees C, above which limited dislocation
      motion is activated shortly before the Ti-wires oxidize. The amorphous FIB
      deposited Pt wires are stable up to 580-650 degrees C where partial
      crystallization is observed in vacuum. Faceted nanoparticles grow on the wire
      surface, growing into free space by surface diffusion and minimizing contact area
      with the underlying wire. The particles are face-centred cubic (fcc) Pt with some
      dissolved Ga. Continued heating results in particle spheroidization, coalescence
      and growth, retaining the fcc structure.

PMID- 15157194
TI  - Using microscopic techniques to reveal the mechanism of anion exchange in
      crystalline co-ordination polymers.
AB  - Co-ordination polymers are currently attracting extensive interest due to their
      potential applications as supramolecular hosts, vessels, and frameworks for
      storage and separations. Many applications rely on the ion exchange capabilities
      of these compounds, and considerable debate surrounds the mechanism by which ion
      exchange occurs in co-ordination polymers. Here AFM and SEM were applied, for the
      first time, to investigate this class of materials. In situ AFM studies revealed
      the mechanism by which anion exchange and the subsequent structural
      transformations of the crystalline co-ordination polymers [[Ag(4,4'
      bipy)]BF(4)](infinity) and [[Ag(4,4'-bipy)]NO(3)](infinity) occur. The process is
      initiated by the dissolution of the metastable crystalline polymer, followed by
      the subsequent crystallization of the new stable phase on the surface of the
      original crystal. The formation of deep clefts in the metastable polymer crystal
      during the transformation allows the solution to access the successive
      crystalline layers. Thus, the entire process can be viewed as a self-perpetuating
      cascade of dissolution and recrystallization throughout the macroscopic crystal.
      SEM data consolidate the findings of AFM. These techniques collectively
      illustrate that the anion exchange, and subsequent structural transformation,
      proceeds via a solvent-mediated mechanism, rather than a purely solid-state one.

PMID- 15157195
TI  - Moderated histogram equalization, an automatic means of enhancing the contrast in
      digital light micrographs reversibly.
AB  - A means for improving the contrast in the images produced from digital light
      micrographs is described that requires no intervention by the experimenter: zero
      order, scaling, tonally independent, moderated histogram equalization. It is
      based upon histogram equalization, which often results in digital light
      micrographs that contain regions that appear to be saturated, negatively biased
      or very grainy. Here a non-decreasing monotonic function is introduced into the
      process, which moderates the changes in contrast that are generated. This method
      is highly effective for all three of the main types of contrast found in digital
      light micrography: bright objects viewed against a dark background, e.g.
      fluorescence and dark-ground or dark-field image data sets; bright and dark
      objects sets against a grey background, e.g. image data sets collected with phase
      or Nomarski differential interference contrast optics; and darker objects set
      against a light background, e.g. views of absorbing specimens. Moreover, it is
      demonstrated that there is a single fixed moderating function, whose actions are
      independent of the number of elements of image data, which works well with all
      types of digital light micrographs, including multimodal or multidimensional
      image data sets. The use of this fixed function is very robust as the appearance
      of the final image is not altered discernibly when it is applied repeatedly to an
      image data set. Consequently, moderated histogram equalization can be applied to
      digital light micrographs as a push-button solution, thereby eliminating biases
      that those undertaking the processing might have introduced during manual
      processing. Finally, moderated histogram equalization yields a mapping function
      and so, through the use of look-up tables, indexes or palettes, the information
      present in the original data file can be preserved while an image with the
      improved contrast is displayed on the monitor screen.

PMID- 15157196
TI  - Off-axis electron holography of electrostatic potentials in unbiased and reverse
      biased focused ion beam milled semiconductor devices.
AB  - Off-axis electron holography in the transmission electron microscope (TEM) is
      used to measure two-dimensional electrostatic potentials in both unbiased and
      reverse biased silicon specimens that each contain a single p-n junction. All the
      specimens are prepared for examination in the TEM using focused ion beam (FIB)
      milling. The in situ electrical biasing experiments make use of a novel specimen
      geometry, which is based on a combination of cleaving and FIB milling. The design
      and construction of an electrical biasing holder are described, and the effects
      of TEM specimen preparation on the electrostatic potential in the specimen, as
      well as on fringing fields beyond the specimen surface, are assessed.

PMID- 15157197
TI  - Robust incremental compensation of the light attenuation with depth in 3D
      fluorescence microscopy.
AB  - Summary Fluorescent signal intensities from confocal laser scanning microscopes
      (CLSM) suffer from several distortions inherent to the method. Namely, layers
      which lie deeper within the specimen are relatively dark due to absorption and
      scattering of both excitation and fluorescent light, photobleaching and/or other
      factors. Because of these effects, a quantitative analysis of images is not
      always possible without correction. Under certain assumptions, the decay of
      intensities can be estimated and used for a partial depth intensity correction.
      In this paper we propose an original robust incremental method for compensating
      the attenuation of intensity signals. Most previous correction methods are more
      or less empirical and based on fitting a decreasing parametric function to the
      section mean intensity curve computed by summing all pixel values in each
      section. The fitted curve is then used for the calculation of correction factors
      for each section and a new compensated sections series is computed. However,
      these methods do not perfectly correct the images. Hence, the algorithm we
      propose for the automatic correction of intensities relies on robust estimation,
      which automatically ignores pixels where measurements deviate from the decay
      model. It is based on techniques adopted from the computer vision literature for
      image motion estimation. The resulting algorithm is used to correct volumes
      acquired in CLSM. An implementation of such a restoration filter is discussed and
      examples of successful restorations are given.

PMID- 15157198
TI  - X-ray omni microscopy.
AB  - The science of wave-field phase retrieval and phase measurement is sufficiently
      mature to permit the routine reconstruction, over a given plane, of the complex
      wave-function associated with certain coherent forward-propagating scalar wave
      fields. This reconstruction gives total knowledge of the information that has
      been encoded in the complex wave-field by passage through a sample of interest.
      Such total knowledge is powerful, because it permits the emulation in software of
      the subsequent action of an infinite variety of coherent imaging systems. Such
      'virtual optics', in which software forms a natural extension of the 'hardware
      optics' in an imaging system, may be useful in contexts such as quantitative atom
      and X-ray imaging, in which optical elements such as beam-splitters and lenses
      can be realized in software rather than optical hardware. Here, we develop the
      requisite theory to describe such hybrid virtual-physical imaging systems, which
      we term 'omni optics' because of their infinite flexibility. We then give an
      experimental demonstration of these ideas by showing that a lensless X-ray point
      projection microscope can, when equipped with the appropriate software, emulate
      an infinite variety of optical imaging systems including those which yield
      interferograms, Zernike phase contrast, Schlieren imaging and diffraction
      enhanced imaging.

PMID- 15157199
TI  - High-resolution wide-field surface plasmon microscopy.
AB  - This paper describes the application of a Kohler illuminated high-resolution wide
      field microscope using surface plasmons to provide the image contrast. The
      response of the microscope to a grating structure in both the Fourier and the
      image planes is presented to demonstrate image formation by surface waves. The
      effect of spatial filtering in the back focal (Fourier) plane to enhance image
      contrast is described. We also discuss how the surface wave contrast mechanism
      affects the imaging performance of the microscope and discuss factors that can be
      expected to lead to even greater improvements in lateral resolution and
      sensitivity.

PMID- 15157200
TI  - Quantitative optical microscope with enhanced resolution using a pixelated liquid
      crystal spatial light modulator.
AB  - This paper presents a brief account of a novel optical microscope, which combines
      the advantages of two well-known techniques, namely phase contrast and phase
      stepping, to provide high contrast imaging and precision measurements. The
      inclusion of a programmable liquid crystal spatial light modulator provides for
      the phase stepping required, while also allowing flexibility for future
      improvements. The results shown reveal an important aspect of the system to
      facilitate quantitative sample measurements, with an enhancement of optical
      resolution compared with conventional optical imaging systems.

PMID- 15157201
TI  - About the role of the various types of secondary electrons (SE; SE; SE) on the
      performance of LVSEM.
AB  - The relative weight, delta(Beta), of the yield of secondary electrons, SE(2),
      induced by the backscattered electrons, BSE, with respect to that, delta(P), of
      secondary electrons, SE(1), induced by the primary electrons, PE, is deduced from
      simple theoretical considerations. At primary energies E(0) larger than E(M)
      (where the total SE yield delta = delta(P) + delta(B) is maximum), the dominant
      role of the backscattering events is established. It is illustrated in SEM by a
      direct comparison of the contrast between SE images and BSE images obtained at
      E(0) approximately 5 keV and E(0) approximately 15 keV on a stratified specimen.
      At energies E(0) less than E(M), the dominant role of SE(1) electrons with
      respect to SE(2) (and SE(3)) is established. It is illustrated by the better
      practical resolution of diamond images obtained with an in-lens detection in low
      voltage SEM E(0) approximately 0.2-1 keV range compared with that obtained with a
      lateral detector. The present contribution illustrates the improved performance
      of LVSEM in terms of contrast and of practical resolution as well as the
      importance of variable voltage methods for subsurface imaging. The common opinion
      that the practical lateral resolution is given by the incident spot diameter is
      also reconsidered in LVSEM.

PMID- 15157202
TI  - Assessment of a protocol for prophylactic antibiotics to prevent perioperative
      infection in urological surgery: a preliminary study.
AB  - BACKGROUND: The aim of the present study was to assess the usability and efficacy
      of our new protocol of prophylactic antibiotic use to prevent perioperative
      infection in urological surgery. METHODS: We prospectively investigated 339 cases
      of typical urological surgery in our department between April 2001 and March 2002
      (group I). We classified surgical procedures into four categories by invasiveness
      and contamination levels: category A, clean less invasive or endoscopic surgery;
      category B, clean invasive or clean contaminated surgery; category C, urinary
      tract diversion using the intestine; and category D, infected surgery.
      Antibiotics were administrated intravenously according to our protocol: category
      A, first or second generation cephems or penicillins during the operative day
      only; category B, first and second generation cephems or penicillins for 3 days;
      and category C, second or third generation cephems for 4 days. Category D was
      excluded from the analysis. To judge perioperative infections, the wound
      condition and general conditions were evaluated in terms of the surgical site
      infection (SSI) as well as remote infection (RI) up to postoperative day (POD)
      14. We retrospectively reviewed 308 patients who underwent urological surgery
      between April 2000 and March 2001 (group II) as reference cases that were
      administered antibiotics without any restriction. RESULTS: Perioperative
      infection rates (SSI + RI) in group I and group II were 25 of 339 (7.4%) and 35
      of 308 (11.4%), respectively. Surgical site infection rates of categories A, B,
      and C in group I were 1.8%, 7.6%, and 30.0%, respectively, while those in group
      II were 2.0%, 7.4%, and 46.2%, respectively. There was no significant difference
      in infection rates in terms of RI and SSI between group I and group II. The
      amounts, as well as the prices, for intravenously administrated antibiotics and
      oral antibiotics decreased to approximately half and one-fifth, respectively.
      CONCLUSION: Our protocol effectively decreased the amount of antibiotics used
      without increasing perioperative infection rates. Thus, our protocol of
      prophylactic antibiotic therapy would be recommended as an appropriate method for
      preventing perioperative infection in urological surgery.

PMID- 15157203
TI  - Prognostic significance of thrombocytosis in renal cell carcinoma patients.
AB  - BACKGROUND: Thrombocytosis has been reported in many types of malignancies and
      has been studied as a prognostic factor. In the present study, we examined the
      incidence of thrombocytosis in patients with renal cell carcinoma (RCC) in order
      to evaluate the prognostic value of thrombocytosis. METHODS: One hundred and
      ninety-six patients treated by radical nephrectomy for RCC were enrolled in this
      study. We divided the patients into a normal platelet count group and a
      thrombocytosis group according to the presurgical platelet count. The two groups
      were compared pathologically and clinically, including prognosis. RESULTS:
      Thrombocytosis was present in 16 patients (8.2%). Platelet counts had normalized
      after nephrectomy in all patients with thrombocytosis. There was no correlation
      between histological type or grade and thrombocytosis. However, there were
      correlations between thrombocytosis and tumor size and tumor stage. Patients with
      thrombocytosis had a worse prognosis than patients without thrombocytosis (P =
      0.0028). When adjusted for stage or tumor size, the correlation was limited to
      low stage (stage 1 + 2: P = 0.0041, stage 3 + 4: P = 0.2983) or small tumors
      (tumor size: </=4 cm, P = 0.0021; 4-7 cm, P = 0.0142; >7 cm, P = 0.8158).
      CONCLUSION: Thrombocytosis is an inexpensive and easy tool with which to evaluate
      the prognosis of RCC patients in daily medical practice.

PMID- 15157204
TI  - Results of the ureteral reimplantation with serous-lined extramural tunnel in
      orthotopic ileal W-neobladder.
AB  - BACKGROUND: Our experience in uretero-ileal anastomosis using the serous-lined
      extramural tunnel in orthotopic ileal W-neobladder is presented. METHODS: Between
      June 1998 and November 2001, 42 patients (40 men and two women) underwent radical
      cystectomy and orthotopic ileal neobladder for invasive bladder cancer. The
      ureters were reimplanted into serous-lined extramural tunnels as described by
      Abol-Enein and Ghoneim. However, we made minor modifications during the ureteral
      reimplantation in cases that necessitated distal ureteral excision and with
      grossly dilated ureters. Evaluation included clinical and radiographic studies to
      determine functional and oncological outcomes. RESULTS: There was no operative
      mortality. The mean follow-up period was 28 months (range 12-52). Early
      complications occurred in four patients (9.5%). An endarterectomy for acute
      popliteal arterial embolism, the excision of the pouchointestinal fistula and a
      temporary colostomy were performed in two of these four patients. The other two
      patients were treated conservatively. Late complications occurred in eight
      patients (19%). Reflux was observed in three renal units (3.7%),
      ureterointestinal strictures in another three renal units (3.7%) and urethroileal
      stenosis in two patients (4.8%). In all cases, stabilization or improvement of
      renal function was achieved. No metabolic complications were observed.
      CONCLUSIONS: Ileal W-neobladder with a serous-lined extramural tunnel is a safe,
      reliable form of lower urinary tract reconstruction. The method can be carried
      out with equal ease in grossly dilated ureters and in cases that necessitate
      distal ureteral excision.

PMID- 15157205
TI  - Prognostic value of nuclear area index in patients with bladder cancer.
AB  - BACKGROUND: To assess the prognostic usefulness of the nuclear area index (NAI),
      a new nuclear morphometric parameter expressed as the mean nuclear area (MNA)
      ratio of cancer to normal transitional cells in patients with bladder cancer, who
      have undergone radical cystectomy. METHODS: Measurements of the nuclear areas of
      cancer and normal transitional cells were carried out on the histological slides
      of 73 patients with bladder cancer. The clinical usefulness of MNA, NAI, grade,
      and TNM categories for the prediction of the cause-specific survival of the
      patients was examined. RESULTS: The median values of MNA and NAI in the 73
      patients were 39 micro m2 and 1.2, respectively. Cause-specific survival rates of
      the patients were calculated according to stage (T1-2 vs T3-4), grade (grade 2 vs
      grade 3), MNA (<39 micro m2 vs>/=39 micro m2) and NAI value (<1.2 vs>/=1.2).
      Using univariate analysis, all these parameters were statistically significant
      prognostic factors. However, by multivariate analysis, NAI was the only
      independent variable for the survival of the patients (P < 0.01). Cause-specific
      survival rates of patients with NAI values of less than 1.2 were significantly
      higher than those with NAI values of 1.2 or more, in both grade 2 and grade 3
      tumors. CONCLUSIONS: These results suggest that NAI could provide improved
      prognostic information for patients with bladder cancer.

PMID- 15157206
TI  - Rectosigmoidal bladder utilizing intussuscepted ileal segment: a surgical
      technique for urinary diversion and experiences in 30 patients.
AB  - BACKGROUND: We previously reported that the ileocecal rectal bladder consists of
      interposition of an intussuscepted ileocecal segment between the ureters and the
      rectum for those in whom the urethra is not available. Although the ileocecal
      rectal bladder has been well accepted by most patients, it requires an extensive
      preparation along the ascending colon. We present a modified operation technique
      (rectosigmoidal bladder) by using the ileal segment alone as an interposing
      antireflux component and by using the sigmoidal segment to augment the rectal
      capacity. METHODS: From February 1993 to July 2002, 30 patients with a median age
      of 64 years underwent construction of a rectosigmoidal bladder. Median follow-up
      period was 26 months (range, 13-125). The follow up was carried out using
      clinical and functional assessments such as evacuation status, serum chemistry
      and radiographic evaluation of the upper urinary tracts and rectosigmoidal pouch.
      To assess the postoperative health-related quality of life, we carried out a
      survey comparison of the ileocecal rectal bladder patients and the rectosigmoidal
      bladder patients. RESULTS: No operative or urinary diversion-related
      postoperative mortality was encountered. All rectosigmoidal bladders had
      sufficient capacity, with no evidence of urinary reflux or daytime incontinence.
      When compared with our previous procedure, the ileocecal rectal bladder, the
      present procedure had advantages with respect to complications with urine-fecal
      leak and acidosis. There were no differences in mean operation time, or in the
      health-related quality of life survey, between the two procedures. CONCLUSIONS:
      Our experience showed that this technique should be considered for those in whom
      the urethra is not available.

PMID- 15157207
TI  - Does transrectal ultrasound guided eight-core prostate biopsy improve cancer
      detection rates in patients with prostate-specific antigen levels of 4.1-10
      ng/mL?
AB  - BACKGROUND: To investigate retrospectively whether the eight-core biopsy method
      improves the prostate cancer detection rate when compared with the standard
      sextant biopsy method in patients with prostate specific antigen (PSA) levels of
      4.1-10 ng/mL. MATERIAL AND METHODS: Of 437 patients whose PSA levels ranged from
      4.1 to 10 ng/mL, 237 underwent a transrectal ultrasound guided sextant biopsy
      (sextant group), and 200 underwent an eight-core biopsy (eight-core group). Eight
      core samples were obtained from each of the far lateral regions in addition to
      the standard sextant biopsy cores. None of the patients had a previous history of
      prostate biopsy. RESULTS: Of the 237 patients in the sextant group, prostate
      cancer was detected in 47 patients (19.8%) and in 50 of the 200 patients in the
      eight- core group (25.0%). The rates of detection in the two methods were not
      statistically significant. However, in patients whose PSA density was less than
      0.1 ng/mL per cc, the cancer detection rates in the sextant group and the eight
      core group were 4.5% and 18.8%, respectively (P = 0.046). The morbidity and
      complications of the eight-core biopsy method were not notable. CONCLUSIONS: Only
      in patients with PSA levels of 4.1-10 ng/mL and density of less than 0.1 ng/mL
      per cc was the eight-core biopsy method an improvement on the sextant biopsy
      method in terms of prostate cancer detection rate. Accordingly, a number of cores
      greater than eight will be required to improve the cancer detection rates in
      patients with PSA levels of 4.1-10 ng/mL and PSA densities of more than 0.1 ng/mL
      per cc.

PMID- 15157208
TI  - Effects of sextant transrectal prostate biopsy plus additional far lateral cores
      in improving cancer detection rates in men with large prostate glands.
AB  - PURPOSE: To determine whether additional, far lateral cores improve the
      diagnostic performance of transrectal sextant biopsy in men with large prostate
      glands. METHODS: Men with prostate volumes of 50 mL or greater in transrectal
      ultrasonography who were suspected of prostatic adenocarcinoma were prospectively
      enrolled. Biopsy criteria were defined as 2.0 ng/mL or greater of serum total
      prostate-specific antigen and/or abnormal findings on digital rectal examination.
      Four cores of far lateral biopsies were added to the standard sextant technique.
      RESULTS: Of 104 patients enrolled in the present study and undergoing biopsy, 14
      (13.5%) were diagnosed as having prostate cancer and 27 (26.0%) were diagnosed as
      having prostatic intraepithelial neoplasia (PIN) or an atypical gland. There were
      no cases where cancer was only detected in the additional cores, whereas
      PIN/atypical gland was uniquely detected from the additional, far lateral sites
      in eight of the 27 patients who were diagnosed with this condition. CONCLUSIONS:
      Although the number of patients diagnosed as having PIN/atypical gland might
      increase with the addition of far lateral cores, this additional sampling does
      not improve cancer detection rates in men with large prostate glands.

PMID- 15157209
TI  - Long-term results of adjuvant hormonal therapy plus radiotherapy following
      radical prostatectomy for patients with pT3N0 or pT3N1 prostate cancer.
AB  - BACKGROUND: The objective of the present study was to evaluate the efficacy of
      adjuvant androgen suppression in conjunction with external beam irradiation after
      radical prostatectomy in patients with pathologically confirmed extraprostatic
      disease. METHODS: Between July 1988 and October 1999, 38 patients with pT3N0 or
      pT3N1 prostate cancer received adjuvant hormonal therapy and external beam
      irradiation following radical retropubic prostatectomy and pelvic
      lymphadenectomy. Administration of luteinizing hormone-releasing hormone analog
      or castration were initiated as an adjuvant androgen suppression within 4 weeks
      after surgery, whereas pelvic irradiation was performed at a median dose of 50 G
      within 3 months after surgery. The prognostic advantage of this combined adjuvant
      therapy was analyzed. RESULTS: During the median observation period of 92 months,
      biochemical recurrence occurred in four of the 38 patients and five patients
      died. Of these five patients, only one died of prostate cancer progression. The
      10-year biochemical recurrence-free, cancer-specific and overall survival rates
      of the 38 patients were 86.7%, 90.9% and 78.7%, respectively. Among several
      factors examined, only tumor grade was significantly associated with biochemical
      recurrence-free survival in these patients; however, there were no factors that
      were independent predictors for biochemical recurrence, based on multivariate
      analysis. Furthermore, biochemical recurrence-free survival in the 38 patients
      was significantly superior to that in 54 patients with locally advanced disease
      who did not receive any postoperative therapies until biochemical recurrence;
      however, there was no significant difference in cancer-specific and overall
      survival between these two groups. CONCLUSION: Despite retrospective analysis
      with a relatively small number of patients, results of the present study suggest
      favorable effects of the combined adjuvant treatments with androgen ablation and
      pelvic irradiation on cancer control for patients with pT3N0 or pT3N1 disease.
      However, considering the absence of a significant difference in cancer-specific
      and overall survival between patients with and without adjuvant treatments, it
      might not be necessary to routinely perform combined hormonal and radiation
      therapies in an adjuvant setting for pT3N0 or pT3N1 prostate cancer.

PMID- 15157210
TI  - Increased detection of clinically significant prostate cancer by additional
      sampling from the anterior lateral horns of the peripheral zone in combination
      with the standard sextant biopsy.
AB  - BACKGROUND: The objective of the present study was to investigate whether
      obtaining an increased number of biopsy cores by sampling additional areas, along
      with the standard sextant biopsy, results in a higher rate of detection of
      potentially insignificant prostate cancer. METHODS: We included 130 patients who
      underwent radical retropubic prostatectomy at our institution between January
      1999 and June 2003 after being diagnosed as having prostate cancer based on
      systematic prostate biopsies that included the areas examined by standard sextant
      biopsies and the bilateral anterior lateral horns (ALHs) of the peripheral zone
      (PZ). Several clinicopathological factors were analyzed, focusing on the
      significance of additional sampling from ALHs in relation to the incidence of
      potentially insignificant cancer, which was defined as organ confined disease
      with tumor volume less than 0.5 cc and Gleason scores <7. RESULTS: According to
      the location of positive biopsy results, these 130 patients were divided into
      three groups as follows: 61 patients (46.9%) with cancer detected from the cores
      taken by standard sextant biopsy only (group A), 15 (11.6%) from ALHs of the PZ
      only (group B), and 54 (41.5%) from both sites (group C). There were no
      significant differences in age, incidence of abnormal digital rectal examination,
      prostate volume, or biopsy Gleason score among these three groups; however,
      pretreatment serum PSA value in group C was significantly higher than that in
      groups A or B. Pathological examinations of radical prostatectomy specimens
      demonstrated that there were no significant differences in the incidence of
      lymphatic invasion, vascular invasion and perineural invasion, or Gleason score
      among the three groups; however, group C had a significantly larger tumor volume
      than groups A or B. Furthermore, insignificant tumor was detected in eight
      patients in group A (13.1%), two in group B (13.3%), and four in group C (7.4%).
      CONCLUSION: These findings suggest that the additional sampling of biopsy cores
      from ALHs does not appear to increase the detection of potentially insignificant
      cancer, and that biological tumor characteristics seem to be similar irrespective
      of cancer location on the needle biopsy.

PMID- 15157212
TI  - Combined adrenal adenoma and myelolipoma in a patient with Cushing's syndrome:
      case report and review of the literature.
AB  - Myelolipoma is an uncommon benign tumor of unknown etiology and adrenal
      myelolipoma is rarely associated with endocrine disorders. We report a 67-year
      old woman with Cushing's syndrome due to left adrenal adenoma associated with
      myelolipoma. The patient underwent laparoscopic left adrenalectomy and
      pathological examination revealed an adrenocortical adenoma associated with
      myelolipoma. To the best of our knowledge, 25 cases of endocrine dysfunction
      associated with myelolipoma have been reported in the English and Japanese
      literature. We review and discuss the pathogenesis of adrenal myelolipoma.

PMID- 15157211
TI  - Reversal of acquired cisplatin resistance by modulation of metallothionein in
      transplanted murine tumors.
AB  - BACKGROUND: The platinum-based chemotherapeutic agent cisplatin is involved in a
      broad spectrum of activities against human systemic malignancies. However,
      acquired resistance to cisplatin reduces its clinical efficacy. Elucidation of
      the molecular basis of cisplatin resistance is required to improve the
      effectiveness of cisplatin. In the present study, the mechanism of acquired
      resistance to cisplatin was studied in C3H mice inoculated with MBT-2 murine
      bladder tumor cells. METHODS: C3H mice were subcutaneously inoculated with 1.0 x
      10(6) MBT-2 cells/mouse on day 0. The mice were given intraperitoneal injections
      of 10 micro mol/kg cisplatin and subcutaneous injections of 1000 micro mol/kg
      propargylglycine, an inhibitor of gamma-cystathionase, once a day for 10
      consecutive days from day 11 to day 20. RESULTS: The metallothionein content of
      the tumors was increased to twice the control level by repeated administration of
      cisplatin. Co-administration of propargylglycine reduced metallothionein
      induction in the tumors and markedly enhanced the antitumor activity of
      cisplatin. In contrast, the glutathione content in the tumors did not change from
      the control level after cisplatin administration. The platinum accumulation in
      tumors treated with cisplatin alone was 1.7-fold greater than when
      propargylglycine was administered concomitantly. The platinum concentrations
      changed in accordance with the metallothionein contents. CONCLUSIONS: These
      observations suggest that metallothionein, but not glutathione or reduced
      platinum accumulation, might play a role in the acquired resistance to cisplatin
      of C3H mice inoculated with MBT-2. Moreover, reversal of this resistance might be
      possible by biochemical modulation of metallothionein.

PMID- 15157213
TI  - Spontaneous peripelvic extravasation of urine due to an inflammatory aneurysm of
      the abdominal aorta.
AB  - A 71-year-old man presented complaining of severe left flank pain. A computed
      tomography scan of the abdomen disclosed a left peripelvic extravasation of urine
      and a 4.0-cm abdominal aortic aneurysm with a significant amount of
      perianeurysmal thickening and prominent left hydroureter. The patient was
      diagnosed as having an inflammatory aneurysm of the abdominal aorta (IAAA) with
      peripelvic extravasations of urine. We report the results of a patient with IAAA
      with ureteral obstruction successfully treated with steroid therapy and a
      ureteral stent.

PMID- 15157214
TI  - Symptomatic renal metastasis 5 years after the management of a squamous cell
      carcinoma of the lung.
AB  - A case of solitary renal metastasis five years after the management of a primary
      squamous cell carcinoma of the lung is presented.

PMID- 15157215
TI  - Metastatic malignant ameloblastoma of the kidneys.
AB  - Ameloblastoma is an uncommon disease in the urological field. The resulting
      tumors or cysts are of odontogenic epithelial origin, are usually benign in
      nature and rarely metastasize to distant organs. We describe a case of metastatic
      ameloblastic carcinoma in both kidneys of a 38-year-old Japanese man, who had a
      history of malignant ameloblastoma and was referred to us for evaluation because
      of gross hematuria and left flank pain. Computed tomography showed irregular
      cystic masses in both kidneys. After we confirmed that the primary lesion and the
      lung metastatic lesion had not recurred, we treated the patient surgically.
      Approximately 4 months postoperatively the patient suffered a local recurrence of
      tumors that was very invasive and aggressive. The patient died 2 months later and
      the autopsy showed local metastasis only, without any metastatic lesion in the
      lungs or other organs. The present case showed that malignant ameloblastoma is
      highly aggressive, and in the case of metastases the prognosis is usually
      extremely poor.

PMID- 15157216
TI  - Cut-to-the-light technique and potassium titanyl phosphate laser ureterotomy for
      complete ureteral obstruction.
AB  - We describe a case of complete ureteral obstruction managed by endoscopic
      recanalization using a 'cut-to-the-light' technique followed by potassium titanyl
      phosphate (KTP) laser ureterotomy. A 53-year-old man developed a ureteral
      obstruction following the transurethral resection of a bladder tumor (TUR-Bt) at
      the left ureteral orifice. The length of the obstructed segment was estimated at
      1 cm based on combined antegrade and retrograde contrast studies.
      Histopathological analysis indicated that the obstruction was caused by fibrosis.
      The 'cut-to-the-light' technique was used for recanalization, and KTP laser
      ureterotomy was performed to obtain an adequate ureteral lumen. A 14 F/7 F
      endoureterotomy stent was removed 6 weeks after the operation. No significant
      complications and no signs of stenosis were observed 24 months after endoscopic
      repair. Endoscopic recanalization is a safe, effective technique for the
      management of a completely obliterated ureteral segment, especially in
      combination with subsequent KTP laser ureterotomy.

PMID- 15157217
TI  - Cavernous hemangioma of the urinary bladder in an 8-year-old child.
AB  - An 8-year-old boy was admitted to Ehime University Hospital, Ehime, Japan, for
      the further investigation of a 5-month episode of gross hematuria accompanied by
      lower abdominal pain. Magnetic resonance imaging revealed a solid tumor measuring
      3 cm in diameter of the bladder wall. Cystoscopy demonstrated a red, wide-based,
      nodular tumor situated on the dome of the bladder. Histological examination of
      tissue taken at hot biopsy showed fibrolipoma. In consideration of potential
      malignancy, a partial cystectomy was carried out after informed consent was
      given. Histological examination of the resected specimen showed it to be
      cavernous hemangioma.

PMID- 15157218
TI  - Medical management of recurrent aggressive angiomyxoma with gonadotropin
      releasing hormone agonist.
AB  - Patients with aggressive angiomyxoma may experience local recurrences. We report
      a case of recurrent aggressive angiomyxoma medically treated successfully with a
      gonadotropin-releasing hormone agonist. A 34-year-old woman with a huge perineal
      tumor underwent an extensive resection of the abdominoperineal tumor combined
      with total pelvic exenteration. Histology showed aggressive angiomyxoma and the
      tumor cells were immunoreactive for estrogen and progesterone receptors. Although
      the patient had experienced no local recurrence for 12 months under adjuvant
      therapy with a gonadotropin-releasing hormone agonist, a recurrence occurred 3
      months after the completion of adjuvant therapy. The patient underwent medical
      treatment with a gonadotropin-releasing hormone agonist and had a complete
      resolution of the recurrent tumor again. Hormonal treatment with a gonadotropin
      releasing hormone agonist can be applied for small primary aggressive
      angiomyxomas in addition to adjuvant therapy for residual tumors.

PMID- 15157219
TI  - Bulbous urethra involved in perineal extraskeletal myxoid chondrosarcoma in a
      child.
AB  - Extraskeletal myxoid chondrosarcoma is a rare soft-tissue sarcoma that usually
      occurs in deep soft tissues, especially those of the proximal extremities and
      limb girdles, but is rare in children. We present an unusual case of a tumor
      arising in the perineum and involving the bulbous urethra in a 21-month-old boy.
      The patient was treated with surgical excision and urethroplasty followed by
      combination chemotherapy.

PMID- 15157220
TI  - A rare case of leiomyosarcoma of the penis with a reappraisal of the literature.
AB  - Primary leiomyosarcomas arising in the penis are rare, with only 29 reported
      cases to date. We review the published records on this entity and describe an
      additional case of penile leiomyosarcoma occurring in a 53-year-old patient who
      underwent postectomy for a firm nodule in the prepuce. Four years later he
      experienced local recurrence which was successfully treated with partial
      penectomy.

PMID- 15157221
TI  - Gastrointestinal stromal tumor presenting as a scrotal mass.
AB  - We describe a huge abdominal gastrointestinal stromal tumor (GIST) extending
      through the right inguinal canal. The reported case illustrates that the scrotum
      might be a place of initial presentation of a GIST growing along preformed
      anatomical structures. Urologists should be aware of this condition that might be
      mistaken for a primarily testicular malignancy.

PMID- 15157222
TI  - The mitochondrial genomes of soft ticks have an arrangement of genes that has
      remained unchanged for over 400 million years.
AB  - There are two major groups of ticks: soft ticks and hard ticks. The hard ticks
      comprise the prostriate ticks and the metastriate ticks. The mitochondrial (mt)
      genomes of one species of prostriate tick and two species of metastriate ticks
      had been sequenced prior to our study. The prostriate tick has the ancestral
      arrangement of mt genes of arthropods, whereas the two metastriate ticks have
      rearrangements of eight genes and duplicate control regions. However, the
      arrangement of genes in the mt genomes of soft ticks had not been studied. We
      sequenced the mt genomes of two species of soft ticks, Carios capensis and
      Ornithodoros moubata, and a metastriate tick, Haemaphysalis flava. We found that
      the soft ticks have the ancestral arrangement of mt genes of arthropods, whereas
      the metastriate tick, H. flava, shares the rearrangements of mt genes and
      duplicate control regions with the other two metastriate ticks that have
      previously been studied. Our study indicates that gene rearrangements and
      duplicate control regions in mt genomes occurred once in the most recent common
      ancestor of metastriate ticks, whereas the ancestral arrangement of arthropods
      has remained unchanged for over 400 million years in the lineages leading to the
      soft ticks and the prostriate ticks.

PMID- 15157223
TI  - Identification of two cDNAs encoding synaptic vesicle protein 2 (SV2)-like
      proteins from epithelial tissues in the cat flea, Ctenocephalides felis.
AB  - Two distinct cDNAs that appear to encode proteins in the synaptic vesicle-2 (SV2)
      family were identified as expressed sequence tags from a Ctenocephalides felis
      hindgut and Malpighian tubule (HMT) cDNA library. To date, SV2 proteins have been
      described only in vertebrates, and have been detected only in synaptic vesicles
      in neuronal and endocrine tissues, where they are thought to regulate synaptic
      vesicle exocytosis. The cDNAs for the C. felis SV2-like proteins SVLP-1 and SVLP
      2 encode predicted full-length proteins of 530 and 726 amino acids, respectively.
      Of characterized proteins, the SVLP protein sequences were most similar to rat
      SV2B. Northern blot analysis revealed that both mRNAs were up-regulated in larval
      stages that feed and in adults after feeding, and were expressed primarily or
      exclusively in the HMT tissues in adult fleas. These results suggest that the
      flea SVLP-1 and SVLP-2 gene products may have roles that are specific for the HMT
      tissues, and may differ in function from vertebrate SV2 proteins.

PMID- 15157224
TI  - The mosquito ribonucleotide reductase R2 gene: ultraviolet light induces
      expression of a novel R2 variant with an internal amino acid deletion.
AB  - Abstract Using RT-PCR, we examined expression of the ribonucleotide reductase R2
      subunit (RNR-R2) in Aedes albopictus mosquito cells after treatment with
      ultraviolet light (UV). In control cells, a predominant band at 1.2 kb
      corresponded to the full-length cDNA. A smaller 650 bp band was unique to UV
      treated cells. Sequence analysis showed that the 650 bp band encoded a protein
      with an internal deletion of 179 amino acids, relative to Ae. albopictus RNR-R2.
      The N-terminal twenty amino acids were identical between AalRNR-R2 and
      AalDeltaR2; downstream of the deletion, the proteins differed at only four
      residues. In AalDeltaR2, the internal deletion spanned five residues critical to
      RNR-R2 enzymatic activity, including a key tyrosine residue that generates an
      essential free radical. The full-length 46 kDa and truncated 25 kDa RNR-R2
      proteins were shown to be expressed on Western blots, and to differ in their
      subcellular localization. Similarly, expression of the two proteins was
      differentially regulated during the cell cycle, and expression of AalDeltaR2
      predominated after UV treatment. AalDeltaR2 resembled a human RNR-R2 variant
      called p53R2, which was induced by agents that damage DNA. As was the case with
      p53R2 and its antisense RNA, levels of AalDeltaR2 were diminished after treatment
      of mosquito cells with RNAi corresponding to p53 from Drosophila melanogaster.
      Examination of the AalRNR-R2 homologue in the Anopheles gambiae genome suggested
      that AalDeltaR2 resulted from precise splicing between Exons 1, 4 and 5,
      eliminating Exons 2 and 3. The likelihood that AalDeltaR2 is a non-enzymatic,
      functional participant in DNA metabolism is suggested by enhancement of DNA
      repair in an in vitro system and by the presence of a similar gene (rnr4) in
      yeast.

PMID- 15157225
TI  - Stage-specific expression of two actin genes in the yellow fever mosquito, Aedes
      aegypti.
AB  - Abstract The expression patterns of two muscle-specific actin genes were studied
      in the yellow fever mosquito, Aedes aegypti. The coding sequence of AeAct-2
      exhibits between 82 and 85% similarity with coding sequences of the Drosophila
      melanogaster and predicted Anopheles gambiae actin genes. The transcription of
      the AeAct-2 gene was differentially regulated during developmental stages with
      higher levels of expression in larvae and lower levels in pupae and adults. The
      AeAct-2 gene is mainly expressed in the head and body wall tissues. Transcripts
      of the AeAct-3 gene are not detectable in larvae until late 4th instar and the
      level increased in male pupae and early male adults. The main site of expression
      of the AeAct-3 gene was the thoracic tissue. Thus, AeAct-3 is the first reported
      male-specific actin gene in mosquitoes.

PMID- 15157226
TI  - Population structure of the malaria vector Anopheles funestus in Senegal based on
      microsatellite and cytogenetic data.
AB  - The study of chromosomal inversions distribution within natural Anopheles
      funestus populations from West Africa revealed high levels of genetic
      structuring. In Burkina Faso, this was interpreted as evidence for incipient
      speciation, and two chromosomal forms were described, namely 'Folonzo' and
      'Kiribina'. Assignation of field collected specimens to one chromosomal form
      depends upon application of an algorithm based on chromosomal inversions. We
      assessed relevance and applicability of this algorithm on An. funestus
      populations from Senegal, where both forms occur. Furthermore, we estimated the
      level of genetic differentiation between populations using microsatellite loci
      spread over the whole genome. Significant genetic differentiation was revealed
      between geographical populations of An. funestus, and the pattern observed
      suggested isolation by distance. Chromosomal heterogeneity was not detected by
      microsatellite markers. Thus, although incipient speciation could not be ruled
      out by our data, our results suggest that differential environmental selection
      pressure acting on inversions should be considered a major factor in shaping
      their distribution in wild An. funestus populations.

PMID- 15157227
TI  - Molecular diversity and phylogenetic analysis of mariner-like transposons in the
      genome of the silkworm Bombyx mori.
AB  - Genome-wide screening of mariner-like elements (MLEs) in the silkworm Bombyx mori
      has revealed the presence of five different types of MLEs (Bmmar1, Bmmar2,
      Bmmar3, Bmmar4 and Bmmar5). We isolated and characterized sixty copies of the
      MLEs representing the five Bmmar types. Their nucleotide sequences, nucleotide
      compositions, deduced transposase sequences, codon preferences, and the copy
      numbers showed extensive variations. Phylogenetic analysis of the sequences
      revealed that Bmmar1, Bmmar2, and Bmmar3 have been in the B. mori genome for a
      long time, while Bmmar4 is probably a recent invader of the genome. Because of
      the long-term association of Bmmar1 and Bmmar2 with the genome, highly mutated
      miniature Bmmar1 and Bmmar2 are widespread in the genome, and the footprints of
      these elements are also present in different silkworm genes. However, miniature
      copies of Bmmar4 were not detected. This recently acquired element has very few
      mutations. None of the characterized copies had functional transposase open
      reading frames. They essentially exist as fossils in the genome.

PMID- 15157229
TI  - Transcriptional regulation in cowpea bruchid guts during adaptation to a plant
      defence protease inhibitor.
AB  - Cowpea bruchid, when fed on a diet containing the soybean cysteine protease
      inhibitor soyacystatin N (scN), activates an array of counter-defence genes to
      adapt to the negative effects of the inhibitor and regain its normal rate of
      feeding and development. A collection of 1920 cDNAs was obtained by differential
      subtraction with cDNAs prepared from guts of the 4th instar larvae of scN-adapted
      (reared on scN-containing diet) and scN-unadapted (reared on regular scN-free
      diet) cowpea bruchids. Subsequent expression profiling using DNA microarray and
      Northern blot analyses identified ninety-four transcript species from this
      collection that are responsive to dietary scN. scN-adapted insects induced genes
      encoding protein and carbohydrate digestive enzymes, probably to help meet their
      carbon and nitrogen requirements. Up-regulation of antimicrobial and
      detoxification protein genes may represent a generalized defence response. Genes
      down-regulated by scN reflected physiological adjustments of the cowpea bruchids
      to scN challenge. A large portion of the responsive genes, presumably involved in
      carrying out the counter-defence response, were of unknown function. The full
      length cDNA of an scN-inducible cathepsin B-like cysteine protease was obtained.
      Its transcriptional response to scN during larval development contrasts with the
      pattern of the cathepsin L family, the major digestive enzymes. These results
      suggest cathepsin B-like cysteine proteases may play a crucial role in cowpea
      bruchid adaptation to dietary scN.

PMID- 15157228
TI  - A novel lectin with a fibrinogen-like domain and its potential involvement in the
      innate immune response of Armigeres subalbatus against bacteria.
AB  - Mosquitoes have an efficient cellular innate immune response that includes
      phagocytosis of microbial pathogens and encapsulation of metozoan parasites. In
      this study, we describe a novel lectin in the mosquito, Armigeres subalbatus
      (aslectin or AL-1). The 1.27 kb cDNA clone for the AL-1 gene (AL-1) encodes a 279
      deduced amino acid sequence that contains a C-terminal fibrinogen-like domain. AL
      1 is transcribed in all life stages. AL-1 mainly exists in the haemolymph of
      adult female mosquitoes, and is upregulated following both Escherichia coli and
      Micrococcus luteus challenge. AL-1 specifically recognizes N-acetyl-d-glucosamine
      and is able to bind both E. coli and M. luteus. These results suggest that AL-1
      might function as a pattern recognition receptor in the immune response in Ar.
      subalbatus.

PMID- 15157230
TI  - Genetic structuring of boll weevil populations in the US based on RAPD markers.
AB  - Abstract Randomly amplified polymorphic DNA (RAPD) analysis was performed to
      infer the magnitude and pattern of genetic differentiation among boll weevil
      populations from eighteen locations across eight US states and north-east Mexico.
      Sixty-seven reproducible bands from six random primers were analysed for genetic
      variation within and between weevil populations. Genetic and geographical
      distances among all populations were positively correlated, reflecting a pattern
      of isolation by distance within a larger metapopulation. Gene flow between south
      central, western and eastern regions is limited, but migration between locations
      within regions appears to be relatively frequent up to distances of approximately
      300-400 km. However, estimates of effective migration were much lower than those
      estimated from mtDNA-RFLP data reported previously.

PMID- 15157231
TI  - Molecular characterization of insulin-like peptide genes and their expression in
      the African malaria mosquito, Anopheles gambiae.
AB  - Of the seven genes encoding insulin-like peptides (ILPs) in the mosquito,
      Anopheles gambiae, four are arrayed proximally as duplicate pairs on chromosome
      three. Amino acid substitutions encoded in the duplicate genes occur in the C
      peptide and not the B and A peptides. Except for one duplicated gene, sequence
      specific transcripts for all other AgamILPs were obtained from female mosquitoes.
      Transcript expression of each AgamILP was determined by RT-PCR in the head,
      thorax, and abdomen of all life stages and both sexes of this mosquito. Two
      AgamILPs were ubiquitously expressed, suggesting a growth factor function,
      whereas the other AgamILPs were expressed primarily in heads, as confirmed by the
      immunostaining of ILPs in the neurosecretory cells of female brains, thus
      indicating a hormonal function.

PMID- 15157232
TI  - Strain-specific quantification of Wolbachia density in Aedes albopictus and
      effects of larval rearing conditions.
AB  - The density of the endosymbiont Wolbachia can influence the expression of the
      crossing sterilities known as cytoplasmic incompatibility (CI), and also its rate
      of maternal transmission. Aedes albopictus mosquitoes contain a superinfection
      with the Wolbachia strains wAlbA and wAlbB. A strain-specific real-time
      quantitative PCR assay was developed and used to quantify relative Wolbachia
      strain densities within individual mosquitoes. The wAlbB strain was consistently
      found to be at higher density than wAlbA, which can explain a slightly lower rate
      of maternal transmission reported for wAlbA. The effects of larval crowding and
      nutritional stress were also examined. Larval crowding always reduced adult size,
      but reduced the density of Wolbachia strains relative to uncrowded conditions
      only if crowding was accompanied by restricted nutrient availability. Crowded
      rearing conditions never resulted in strain segregation or in a reduction in the
      penetrance of CI, however. The rate of maternal transmission and the penetrance
      of CI are the two most important variables that determine relative Wolbachia
      population invasion dynamics, and both are considerably higher here than have
      been reported in the Drosophila simulans model system.

PMID- 15157233
TI  - The moleskin gene product is essential for Caudal-mediated constitutive
      antifungal Drosomycin gene expression in Drosophila epithelia.
AB  - The homeobox gene, Caudal, encodes the DNA-binding nuclear transcription factor
      that plays a crucial role during development and innate immune response. The
      Drosophila homologue of importin-7 (DIM-7), encoded by moleskin, was identified
      as a Caudal-interacting molecule during yeast two-hybrid screening. Both mutation
      of the minimal region of Caudal responsible for moleskin binding and RNA
      interference (RNAi) of moleskin dramatically inhibited the Caudal nuclear
      localization. Furthermore, Caudal-mediated constitutive expression of antifungal
      Drosomycin gene was severely affected in the moleskin-RNAi flies, showing a local
      Drosomycin expression pattern indistinguishable from that of the Caudal-RNAi
      flies. These in vivo data suggest that DIM-7 mediates Caudal nuclear
      localization, which is important for the proper Caudal function necessary for
      regulating innate immune genes in Drosophila.

PMID- 15157234
TI  - Cloning, expression and partial characterization of a Haemaphysalis longicornis
      and a Rhipicephalus appendiculatus glutathione S-transferase.
AB  - The ticks Haemaphysalis longicornis and Rhipicephalus appendiculatus are
      important parasites worldwide. The current method for control of cattle ticks
      involves the use of chemicals. Nevertheless, parasite resistance is an ever
      increasing global problem. Glutathione S-transferases (GSTs) play a central role
      in detoxication of xenobiotic and endogenous compounds. Several authors have
      noted that an increase in GST activity is associated with resistance to
      insecticides and acaricides. In the present study, we report the cloning and
      expression of GST cDNAs from H. longicornis and R. appendiculatus. In addition,
      we determine the effect of three acaricides (ethion, deltamethrin and diazinon)
      on the enzymatic activity of rGSTs.

PMID- 15157235
TI  - Cloning and expression of type XII collagen isoforms during bovine adipogenesis.
AB  - In order to isolate candidate genes involved in bovine adipocyte differentiation,
      we have constructed a subtraction library from a clonal bovine intra-muscular pre
      adipocyte (BIP) cell line using the suppression subtractive hybridization method.
      We have isolated a set of subtracted cDNA fragments whose respective mRNA levels
      are up-regulated during the adipogenic differentiation of BIP cells, and cloned
      cDNAs from a differentiated BIP-lambda ZAP II cDNA library. Two cDNA clones were
      highly homologous to the sequence of mouse and human type XII collagen alpha-1,
      determined by a BLAST homology search. As type XII collagen has been reported to
      have four types of splicing isoform, two clones were determined to be XII-1 and
      XII-2 splicing isoforms, respectively, because of a difference in the C-terminal
      NC1 domain. From the expression analysis of type XII collagen, the XIIA-2 isoform
      was mainly expressed in differentiated BIP cells and adipose tissues. Although
      the function of type XII collagen has not been established as yet, these results
      suggest that type XII collagen may be associated with adipocyte differentiation
      and adipose formation in cattle and is a potentially useful marker for
      adipogenesis.

PMID- 15157236
TI  - Serial cultivation of chicken keratinocytes, a composite cell type that
      accumulates lipids and synthesizes a novel beta-keratin.
AB  - The epidermis of birds differs from that of mammals by the presence of
      intracellular lipid droplets and the absence of sebaceous glands. We describe
      here the cultivation of chicken epidermal keratinocytes; these cells cannot be
      grown in medium supplemented with the usual fetal bovine serum even in the
      presence of supporting 3T3 cells, but they can grow from single cells in the
      presence of supporting 3T3 cells and 10% chicken serum. As revealed by their cell
      structure, their protein composition, and their gene expression, chicken
      keratinocytes possess the general properties of mammalian keratinocytes. They
      ultimately undergo in culture a process of terminal differentiation in which
      their nucleus is destroyed and a cornified envelope is formed. Chicken
      keratinocytes also show important properties that mammalian keratinocytes do not
      possess: they accumulate neutral lipids, usually in the form of a single
      perinuclear droplet; they accumulate carotenoids; they synthesize beta-keratins;
      and their multiplication requires a non-lipid factor, present in chicken serum
      but not in fetal calf serum. The lipid-synthesizing function of sebocytes in
      mammals is carried out by the keratinocytes themselves in birds. The availability
      of cultured chicken keratinocytes should allow studies that were hitherto
      impossible such as the tracing of the keratinocyte lineage during development of
      the chicken embryo and the investigation of the complete life cycle of viruses
      that require specific chicken keratinocyte products (such as Marek's disease
      virus).

PMID- 15157237
TI  - A three-dimensional organotypic culture of the human uterine exocervix for
      studying mucosal epithelial differentiation and migrating leukocytes.
AB  - We report on a three-dimensional organotypic culture in vitro of explants from
      the human uterine exocervix. Exocervical fragments (2-3 mm3) from pre-menopausal
      women were cultured on sponges submerged in Dulbecco's Modified Eagle's Medium
      containing p-nonylphenol and 10% fetal bovine serum for up to 3 weeks and the
      viability and cellular responses were assayed. The fragments were analyzed by
      immunohistochemistry for the expression and distribution of a broad spectrum of
      cellular markers: p63, Ki-67, involucrin, high molecular weight cytokeratins,
      estrogen receptor-alpha, vimentin, CD45, and CD31. The fragments preserved their
      tissue architecture and cellular heterogeneity comparable to that observed in
      exocervical tissue in vivo. Prior to culture, the original epithelium was
      composed of stratified multilayered keratinocytes with integrated
      monocyte/dendritic-like cells in the basal and suprabasal layers. The epithelium
      began to exfoliate in culture and within 4 days appeared to have lost its
      differentiated high-zone layers of keratinocytes. After 10 days a new epithelium,
      slightly different from the original one, was formed; it displayed an increasing
      prominence of basal and suprabasal keratinocyte layers, containing infiltrating
      leukocytes that had probably migrated from the submucosa. The epithelium
      subsequently lost its organization, concomitant with a progressive involution of
      the stroma. Subepithelial capillaries appeared to be well maintained throughout
      the culture period. Aside from the maintenance of cellular heterogeneity within
      the fragments of exocervix, these culture systems are a valuable tool for
      studying the mechanisms of epithelial regeneration, and may prove to be a useful
      model for studying mucosal immunity.

PMID- 15157238
TI  - Epithelio-mesenchymal transition in a neoplastic ovarian epithelial hybrid cell
      line.
AB  - A hybrid cell line, IOSE-Ov29, was created through fusion of cells from the human
      ovarian adenocarcinoma line OVCAR3 and the non-tumorigenic SV40 Tag-transfected
      human ovarian surface epithelial line IOSE-29. OVCAR3 cells exhibit a
      differentiated epithelial phenotype, whereas line IOSE-29 expresses mesenchymal
      characteristics that were acquired in culture by epithelio-mesenchymal
      transition. Microsatellite analysis, comparative genomic hybridization (CGH), and
      MFISH showed the genotype of the IOSE-Ov29 cells to contain components of both
      parent cell lines, but to be predominantly OVCAR3 derived. IOSE-Ov29 resembled
      OVCAR3 and differed from IOSE-29 as shown by its unlimited life span,
      tumorigenicity, epithelial morphology, keratin, occludin, E-cadherin and CA125
      expression, increased expression of kinases of the PI3K pathway, and loss of cGMP
      dependent protein kinase expression. IOSE-29-derived properties included SV40 Tag
      expression, growth inhibition by activin, collagen type III secretion, increased
      adhesion and spreading on tissue culture plastic, and increased growth rate.
      Proliferation of all three lines was stimulated by FSH and ATP and inhibited by
      GnRH I and GnRH II. Interestingly, IOSE-Ov29 was more anchorage independent than
      either parent line and was the only line that invaded Matrigel in Boyden chambers
      and formed invasive branches in collagen gels. The results indicate that IOSE
      Ov29 is an IOSE-29/OVCAR3 hybrid, which differs from both parent lines
      genetically and phenotypically. Unexpectedly, fusion with the non-tumorigenic
      IOSE-29 cells enhanced malignancy-associated characteristics of OVCAR3,
      presumably as a result of the expression of IOSE-29-derived mesenchymal
      properties that are usually acquired by carcinoma cells through epithelio
      mesenchymal transition during metastatic progression.

PMID- 15157239
TI  - Culture of large vessel endothelial cells on floating collagen gels promotes a
      phenotype characteristic of endothelium in vivo.
AB  - The vascular endothelium in vivo is a remarkably quiescent cell layer that
      displays a highly differentiated and tissue-specific phenotype. Once established
      in culture, endothelial cells (EC) are phenotypically different from their in
      situ counterparts, displaying altered gene expression, increased mitotic index,
      and decreased cell density. To determine whether manipulating the
      microenvironment of cells in vitro would lead to a more differentiated phenotype,
      we cultured bovine aortic EC on floating collagen gels. EC cultured to confluence
      on floating gels for 24 or 48 hr display mitotic indices nearly identical to
      those of quiescent endothelium in vivo, nearly two log orders lower than that of
      EC cultured to confluence on plastic, and cell density on floating gels also
      resembles that observed for endothelium in vivo. Culture of EC on floating gels
      leads to decreased expression of platelet-derived growth factor-B, fibronectin,
      and fibronectin isoform ED-B, and increased levels of connexin40, relative to
      cells cultured on plastic. We conclude that culture of bovine aortic EC under
      standard culture conditions results in a phenotype reminiscent of development
      and/or wound healing, and that culturing them on a floating collagen gel leads to
      a more differentiated phenotype, reminiscent of that observed for large vessel EC
      in vivo.

PMID- 15157240
TI  - Early endodermal expression of the Xenopus Endodermin gene is driven by
      regulatory sequences containing essential Sox protein-binding elements.
AB  - The Endodermin gene is expressed in the early endoderm and the Spemann organizer
      of Xenopus embryos. It has previously been shown to be a direct target of the
      early endodermal transcription factor Xsox17 (Clements et al., 2003, Mech Dev
      120:337-348). Here we identify two adjacent control elements in the Endodermin
      promoter; these drive transcription of the gene in late-gastrula endoderm and
      contain consensus Sox-binding sites. We have analyzed one element in detail and
      show that it responds directly to Xsox17 and that the Sox sites are essential for
      endodermal expression in transgenic embryos. However, flanking regions on both
      sides are also essential, indicating that Xsox17 acts in concert with several DNA
      binding partners.

PMID- 15157241
TI  - Transfusion medicine illustrated. Unnecessary transfusions due to
      pseudothrombocytopenia.

PMID- 15157242
TI  - Apheresis platelet transfusions: does ABO matter?

PMID- 15157243
TI  - Significant numbers of apheresis-derived group O platelet units have "high-titer"
      anti-A/A,B: implications for transfusion policy.
AB  - Transfusion of group O single-donor apheresis PLTs (SDP) to group A recipients
      has resulted in intravascular hemolysis and mortality. Owing to low availability
      of type-specific SDPs, transfusion services sometimes issue ABO-mismatched PLTs.
      After observing two cases of acute hemolysis following infusion of O SDPs to
      group A patients, where both recipient eluates revealed anti-A specificity, a
      prospective study to determine the prevalence of "high-titer" anti-A/A,B in group
      O SDPs was commenced. One hundred group O SDP samples were tested. Titers of at
      least 64 and/or 256 from either buffered (generally reflective of IgM antibodies)
      or anti-IgG gel cards, respectively, were considered critically high. Twenty
      eight and 39 percent of samples revealed critically high anti-A/A,B IgM and IgG
      titers, respectively. IgM titers were at 1:64 (18%), 128 (6%), and 256 (4%),
      whereas IgG titers were at 1:256 (28%), 512 (7%), 1024 (2%), and 2048 (2%). The
      prevalence of critical anti-A/A,B titers in group O SDPs is relatively high.
      Thus, the risk of minor side ABO mismatch and potential intravascular hemolysis
      during group O SDP transfusion to group A recipients may be significant. Based on
      these data, a policy was instituted to test anti-A/A,B titers in O SDPs prior to
      "out-of-group" transfusion.

PMID- 15157244
TI  - Blood transfusion rates in the care of acute trauma.
AB  - BACKGROUND: Ten to 15 percent of all RBCs are used in the care of injury.
      Understanding patterns of RBC use is important. Routine resource allocation,
      planning for mass casualty situations, designing research, and optimizing triage
      all can be usefully informed. STUDY DESIGN AND METHODS: Blood Bank and Trauma
      Registry records were linked to produce a transfused blood product list for each
      patient directly admitted from the scene of injury to a large Level 1 trauma
      center in calendar year 2000. Categorical associations between demographic data,
      Injury Severity Score, transfused products, and outcome were sought. Special
      attention was paid to the groups receiving uncross-matched RBCs and more than 10
      units of RBCs. RESULTS: Eight percent (479/5645) of acute trauma patients
      received RBCs, using 5219 units and sustaining an overall mortality of 27
      percent. Sixty-two percent of RBCs were given in the first 24 hours of care.
      Three percent of patients (147 injured) received more than 10 units and received
      71 percent of all RBCs given. Mortality in this cohort was 39 percent. Ninety
      percent of the patients who received more than 10 units of RBCs received plasma,
      and 71 percent received PLTs. CONCLUSIONS: A small number of patients receives
      most of the blood products used in the treatment of injury. Transfusion of more
      than 10 units of RBCs identifies a subgroup where most patients received plasma
      and PLTs to treat actual or anticipated dilutional coagulopathy. There is no
      clear threshold beyond which blood use is futile.

PMID- 15157245
TI  - Incidence and specificity of HLA antibodies in multitransfused patients with
      acquired aplastic anemia.
AB  - BACKGROUND: This study aimed to establish the prevalence and characteristics of
      anti-HLA in antibody acquired aplastic anemia patients following cessation of
      antithymocyte globulin therapy and to characterize antibody in terms of epitope
      specificity. STUDY DESIGN AND METHODS: One hundred and fifty multitransfused,
      untransplanted patients from eight European centers were investigated by
      serologic methods. RESULTS: Sixty-two percent were antibody positive. Eighteen
      HLA-Class-I-specific antibodies (15 IgG, 3 IgM) were identified in 13 patients;
      13 antibodies were specific for HLA-A epitopes and 5 for HLA-B. Epitope analysis
      identified significant correlation between serum reactivity and amino acid
      substitutions associated with HLA-Class-I epitopes. An excess of antibodies to
      HLA-A1-associated cross-reactive groups was identified. There was no significant
      difference in antibody frequency in patients taking cyclosporine compared to
      those who were not. CONCLUSION: Data suggested a contribution from B cell memory
      of alloantigens introduced during pregnancy. In some cases, antibody production
      continued many years after the last transfusion, and although the target varied
      between individual patients, the antibody to HLA was focused on a few specific
      Class I epitopes, the majority of which mapped to the HLA-A molecule.

PMID- 15157246
TI  - Anemia and its treatment and outcomes in persons infected with human
      immunodeficiency virus.
AB  - BACKGROUND: Anemia is a common comorbidity with HIV. Before the highly active
      antiretroviral therapy (HAART) era, anemia was found to be associated with
      decreased survival. This study examined the prevalence of anemia since HAART's
      availability and the associations between anemia treatments and survival. STUDY
      DESIGN AND METHODS: Anemia prevalence in a cohort of HIV-infected persons was
      described. In a smaller cohort of HIV-infected anemic patients, survival was
      modeled with a time-dependent proportional hazards regression model adjusting for
      CD4+ T-lymphocyte count, plasma HIV RNA concentration load, hemoglobin (Hb)
      level, and other factors. RESULTS: Anemia (Hb level < 10.5 g/dL, or physician
      diagnosis) decreased from 13 to 5 percent (p < 0.05) in 1996 through 2001. Anemia
      prevalence was highest (24-35%) and did not decrease among patients with CD4
      count less than 100 cells per mL. In total, 216 severely anemic HIV-infected
      individuals (mean Hb level, 8.1 g/dL) followed for a median of 13 months had a 37
      percent mortality rate. Of these, 22 percent were untreated (13% mortality rate),
      42 percent received transfusion alone (52% mortality), 12 percent received
      epoetin alfa alone (19% mortality), and 24 percent received both (47% mortality).
      Transfusion was associated with a threefold excess mortality risk, but epoetin
      alfa prescription was not associated with mortality. CONCLUSION: The prevalence
      of anemia decreased in the HAART era, and transfusion was positively associated
      with risk of death, suggesting limiting use of transfusions in nonemergency
      situations.

PMID- 15157247
TI  - Efficacy and safety of phlebotomy to reduce transfusional iron overload in adult,
      long-term survivors of acute leukemia.
AB  - BACKGROUND: Transfusional iron overload is a frequent finding in long-term
      survivors of acute leukemia (AL). Only a few studies have reported the results of
      iron depletion therapy in this category of patients. STUDY DESIGN AND METHODS:
      Between January 1996 and July 2003, 26 consecutive adult patients who achieved
      complete remission of AL and developed transfusional iron overload underwent a
      weekly phlebotomy program at our transfusion center. Serum ferritin levels and
      transferrin saturation were monitored during the iron depletion therapy and the
      follow-up period. These AL patients were also checked for the presence of 12
      hereditary hemochromatosis (HH) gene mutations. RESULTS: After a mean follow-up
      of 57.8 months, therapeutic phlebotomy (mean number of units collected, 36.6) was
      effective in reducing mean ferritin concentration and transferrin saturation from
      1726.9 to 93.0 mg per L and from 54.7 to 23.3 percent, respectively. The presence
      of a HH gene mutation did not influence initial iron status or response to
      treatment. The phlebotomy program was well tolerated and no adverse events were
      recorded during or after collection. In three cases the time between phlebotomies
      was increased because of patient's poor compliance or low Hb levels. CONCLUSION:
      Our study shows that phlebotomies are a safe and effective method for reducing
      iron over-load in multiply transfused long-term AL survivors with secondary
      hemochromatosis.

PMID- 15157249
TI  - HPA-5b (Bra) neonatal alloimmune thrombocytopenia in Quebec: incidence and
      clinical outcome in 31 cases.
AB  - BACKGROUND: Clinical detection of neonatal allo-immune thrombocytopenia (NAITP)
      is often less than the incidence predicted in prospective studies. The aims of
      this study were to calculate the observed and expected incidence of NAITP in
      Quebec, Canada, and to evaluate the clinical outcome of infants with anti-HPA-5b
      NAITP. STUDY DESIGN AND METHODS: Records from 1998 to 2002 of the only PLT
      serology laboratory for the province of Quebec were reviewed, as were hospital
      charts of all HPA-5 cases. The number of expected NAITP cases was estimated with
      known alloantigen gene frequencies. RESULTS: Ninety cases of NAITP were
      identified. The clinical detection rate was 1 in 4100, with 9 to 30 percent of
      expected HPA-1a and 11 to 23 percent of expected HPA-5b NAITP cases detected.
      Seventy-eight percent of cases of HPA-5b NAITP were asymptomatic. Sixty-three
      percent of all deliveries but 94 percent of HPA-5b cases occurred in hospitals
      performing cord blood PLT counts. CONCLUSION: The NAITP detection rate was 25 to
      50 percent of the rate reported in prospective trials. The less severe clinical
      presentation of NAITP owing to HPA-5b was confirmed. The frequent routine
      determination of cord blood PLT counts may explain increased detection of
      asymptomatic NAITP involving anti-HPA-5b.

PMID- 15157248
TI  - An immediate hemolytic reaction induced by repeated administration of
      oxaliplatin.
AB  - BACKGROUND: Platinum-based chemotherapy agents have been associated with
      potentially fatal acute immune-mediated hemolytic anemia. The target antigen,
      cause of the positive direct antiglobulin test (DAT) and mechanism of hemolysis
      have been the subject of controversy. CASE REPORT: We report a patient who
      developed a DAT-positive hemolytic episode after a red cell (RBC) transfusion was
      delivered during the infusion of her 17th cycle of oxaliplatin. Standard
      pretransfusion testing was uncomplicated; however, after infusion, the serum was
      no longer compatible with the transfused units and a strong (4+) panreactive IgG
      antibody was detected. RESULTS: The patient's serum from 10 days after the
      episode, only when therapeutic concentrations of oxaliplatin were added, reacted
      with all RBCs tested using the indirect antiglobulin test (IAT) (3+). The effect
      was retained with a purified IgG fraction and almost eliminated with IgG-depleted
      serum. Immunoprecipitation analysis revealed a band with the molecular weight of
      the Band 3 anion channel only in the presence of the patient's serum and
      oxaliplatin. CONCLUSION: Our investigations indicated that oxaliplatin interacted
      with both an IgG antibody and a RBC membrane epitope probably located on the Band
      3 anion channel.

PMID- 15157250
TI  - Persistence of cefotetan on red blood cells.
AB  - BACKGROUND: Cefotetan can cause severe immune hemolytic anemia that may persist
      long after the drug is discontinued. To study the binding of cefotetan to RBCs,
      patients who received cefotetan were followed and tested for the presence of
      antibody to cefotetan. STUDY DESIGN AND METHODS: Patients receiving cefotetan
      were identified from pharmacy and nursing records. Blood samples obtained for
      routine hematology tests were analyzed. Cefotetan binding to patients' RBCs was
      tested using a previously characterized high-titer anticefotetan serum by gel
      technique. To determine the minimum amount of drug necessary for binding to
      occur, RBCs were incubated with serial dilutions of cefotetan at pH 7.4. RESULTS:
      Sixty patients receiving 1 to 25 g i.v. (median, 2 g) of cefotetan were followed
      for 1 to 123 days (median, 18 days). All were initially positive, for cefotetan
      on RBCs. Positivity persisted for up to 98 days after the last dose of drug.
      Fifteen patients became negative during follow-up. The first negative sample
      occurred at Day 30 to 123. Using the midpoint between the last positive and first
      negative to estimate of the duration of positivity, we estimate that cefotetan
      remains RBC-bound for 16.5 to 92 days (median, 67.5 days). During the follow-up
      period, five patients developed anticefotetan detectable in the serum. Twenty
      patients receiving other cephalosporin antibiotics showed no specific reactivity
      of their RBCs with anticefotetan. In vitro studies showed a minimum necessary
      drug concentration of 1 micromol/L at physiologic pH, which was not significantly
      altered by RBC pretreatment with ficin, sialydase, or DTT. CONCLUSIONS: Cefotetan
      is tightly bound to RBCs after intravenous administration and remains detectable
      for weeks after the last dose. Antibodies to cefotetan may occur in about 8
      percent of patients receiving the drug. The minimum necessary concentration for
      RBC binding is low compared to an estimated plasma concentration of 240
      micromol/L from a single i.v. dose of 1 g.

PMID- 15157251
TI  - RH locus contraction in a novel Dc-/D-- genotype resulting from separate genetic
      recombination events.
AB  - BACKGROUND: The rare phenotypes Dc- and D-- lack the expression of E/e and CcEe
      antigens, respectively; their cotransmission in a single family has not been
      reported. STUDY DESIGN AND METHODS: Six members of a Chinese family with two
      exhibiting the Dc- phenotype were studied using standard serologic methods. Rh
      genotypes were analyzed by Southern blot, and RH loci, by exon PCR. Rh
      transcripts were characterized by gene-specific RT-PCR and sequencing. RESULTS:
      Although Rh typing detected two members as Dc- homozygotes, RFLP analysis and
      exon PCR showed them to be Dc- heterozygotes with a partial deletion of RHCE.
      cDNA sequencing showed the expression in the family of normal RHD and RHCe as
      well as hybrid transcripts, RHD(1-9)/RHCE(10) and RHCE(1-3)/RHD(4-10). Thus, the
      Dc- members had the genotype of Dc-/ D-- and expressed both hybrid genes that
      were inherited from their parents, respectively. DISCUSSION: This is the first
      demonstration in a family that the Dc- and D-- complexes neither are linked with
      a normal RHD or RHCE gene. The segregation of these two different hybrid genes
      with single break points suggests their independent genetic origin and provides
      molecular insights into the dynamic nature of genomic rearrangements leading to
      RH locus contraction.

PMID- 15157252
TI  - Analysis of ABO discrepancies occurring in 35 French hospitals.
AB  - BACKGROUND: The risk of immunohemolytic reaction owing to ABO-mismatched
      mistransfusion is 100 to 1000 times higher than the risk of viral infection. Like
      analysis of incident reports, evaluation of near-miss events can provide useful
      insight into hazardous situations for mis-matched blood transfusion. The aim of
      this prospective study was to assess the incidence and root causes of all ABO
      discrepancies, detected by a central hematology laboratory, in blood samples
      referred from 35 district hospitals. STUDY DESIGN AND METHODS: ABO discrepancies
      were detected by comparing either two current blood specimens or a current and
      historical specimen collected over a 5-year study period. Discrepancies were
      investigated by retyping new samples, checking sample identification, and
      reviewing previous hospital records. RESULTS: A total of 118 ABO discrepancies
      were discovered in a series of 407,769 tests carried out during the study period.
      The incidence of ABO discrepancies was 1 per 3,400. This figure was 10 times
      higher than the incidence of ABO-mismatched transfusions. Most of these ABO
      discrepancies were due to phlebotomy errors, that is, collection from wrong
      patient. The second most common cause involved clerical errors during patient
      registration or identification. CONCLUSION: ABO discrepancies can result from
      errors made not only by the medical staff during phlebotomy but also to by the
      clerical staff during registration and identification. These findings emphasize
      the need to standardize data transmission between health care personnel.

PMID- 15157253
TI  - Effect of thrombopoietin alone and a combination of cytochalasin B and ethylene
      glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid-AM on the survival and
      function of autologous baboon platelets stored at 4 degrees C for as long as 5
      days.
AB  - BACKGROUND: PLTs stored at 22 degrees C have the potential for bacterial
      contamination, a problem that could be reduced by 4 degrees C storage.
      Nevertheless, PLTs stored at 4 degrees C exhibit a significantly reduced life
      span. This study was performed to determine whether treatment of PLTs with
      thrombopoietin or cytochalasin B plus ethylene glycol bis(beta-aminoethyl ether)
      N,N'-tetraacetic acid (EGTA)-AM could prevent exponential loss of PLTs stored at
      4 degrees C. STUDY DESIGN AND METHODS: Autologous baboon PLTs were stored at 22
      or 4 degrees C. The 4 degrees C stored PLTs were treated with 1.5 ng per mL
      thrombopoietin, with 1 micro mol per L cytochalasin B, and 80 micromol per L EGTA
      AM (cyto-EGTA) or not treated and labeled with (111)In-oxine to study their in
      vivo recovery and life span. PLT function was assessed by correction of an
      aspirin-induced prolonged bleeding time. Aggregation responses and morphology
      were also assessed. RESULTS: PLTs stored at 22 degrees C had normal in vivo
      recovery and linear survival. PLTs stored at 4 degrees C, whether or not they
      were treated with thrombopoietin, had normal recovery and exponential survival.
      Aggregation of cyto-EGTA-treated PLTs was similar for PLTs stored at 4 degrees C
      and fresh PLTs, but decreased in PLTs stored at 22 degrees C for 5 days. The
      addition of cyto-EGTA to PLTs before 4 degrees C storage inhibited morphologic
      changes that occurred in PLTs stored at 22 degrees C and cold-induced PLT
      clumping, but did not prevent exponential disappearance of the PLTs. CONCLUSION:
      Addition of thrombopoietin or cyto-chalasin B and EGTA-AM to PLTs before 4
      degrees C storage did not prevent exponential loss of PLTs.

PMID- 15157254
TI  - Posttransfusion 24-hour recovery and subsequent survival of allogeneic red blood
      cells in the bloodstream of newborn infants.
AB  - BACKGROUND: The feasibility, efficacy, and safety of transfusing stored
      allogeneic RBCs has been demonstrated for small-volume transfusions given to
      infants. We measured the posttransfusion recovery and intravascular survival of
      allogeneic RBCs stored up to 42 days to further elucidate their efficacy. STUDY
      DESIGN AND METHODS: Preterm infants were transfused with 1.0 mL of biotinylated
      RBCs plus 15 mL per kg of unlabeled allogeneic RBCs. Posttransfusion infant blood
      samples obtained at 10 minutes, and at 1, 2, 4, 7, 10, 14, and 21 days were used
      to determine the 24-hour posttransfusion recovery (PTR(24)), mean potential life
      span (MPL), and time to disappearance of 50 percent of biotinylated RBCs (T(50)).
      RESULTS: No significant differences were found between allogeneic RBCs stored 1
      to 21 days versus 22 to 42 days for PTR(24), MPL, or T(50), indicating comparable
      posttransfusion circulation, regardless of storage age. Although MPL and T(50)
      values in infants using biotinylated RBCs were short, compared to those expected
      using chromium-labeled RBCs in adults, they agreed with results reported by
      others using biotinylated RBCs. CONCLUSIONS: Satisfactory posttransfusion RBC
      recovery and survival, measured with biotinylated RBCs, support earlier clinical
      trials that established the efficacy and safety of stored allogeneic RBCs for
      small-volume transfusions given to infants. The relatively short MPL and T(50)
      values in some infants may underestimate true survival due to ongoing
      erythropoiesis and infant growth with commensurate increase in blood volume
      during the time of RBC survival studies. Because values in infants differ from
      those expected using chromium-labeled RBCs in adults, and the number of
      posttransfusion determinations was few, additional studies are needed to define
      the mechanisms involved.

PMID- 15157255
TI  - Photochemical inactivation of selected viruses and bacteria in platelet
      concentrates using riboflavin and light.
AB  - BACKGROUND: A medical device is being developed for the reduction of pathogens in
      PLT concentrates (PCs). The device uses broadband UV light and the compound
      riboflavin (vitamin B(2)). STUDY DESIGN AND METHODS: Pathogens were added to
      single-donor PLTs. After treatment, the infectivity of each pathogen was measured
      using established biologic assays. In vitro PLT performance was evaluated after
      treatment and after 5 days of storage using a panel of 10 in-vitro cell quality
      assays. RESULTS: In studies with viral pathogens, the Pathogen Reduction
      Technology (PRT) system provided average log reduction factors of 4.46 +/- 0.39
      for intracellular HIV, 5.93 +/- 0.20 for cells associated HIV, and 5.19 +/- 0.50
      for West Nile virus. For the nonenveloped porcine parvovirus, a reduction factor
      greater than 5.0 log was observed. Staphylococcus epidermidis and Escherichia
      coli bacteria were also tested with observed reduction factors to the limits of
      detection of 4.0 log or greater. PLT cell quality was adequately maintained after
      treatment and during storage. Although P-selectin expression, glucose
      consumption, and lactate production increased relative to controls, this was not
      beyond accepted levels. The pH of treated PCs also decreased slightly relative to
      control PLTs on Days 1 and 5. CONCLUSION: The data indicate that the device
      successfully reduced the number of selected pathogens in PCs. Despite the fact
      that significant differences exist between treated and control in-vitro
      variables, it is speculated that the clinical effectiveness of both products will
      not be significantly different, based on comparison to historical data for
      products in routine clinical use today.

PMID- 15157256
TI  - West Nile virus in plasma is highly sensitive to methylene blue-light treatment.
AB  - BACKGROUND: The epidemic of West Nile virus (WNV) in the US resulted in cases of
      transfusion-transmitted WNV. Effective pathogen reduction methods could have
      removed this infectious agent from the blood supply We have evaluated the
      efficacy of photodynamic treatment of fresh frozen plasma (FFP) with methylene
      blue (MB), a decontamination method applied in several European countries. STUDY
      DESIGN AND METHODS: FFP units (300 ml each) were spiked with WNV. MB was added,
      and the units were illuminated with white or monochromatic yellow light. WNV
      infectivity was determined by bioassay. WNV-RNA was quantitated by real-time PCR.
      The inactivation of WNV was investigated under standard and under suboptimal
      conditions, respectively. In addition, rechallenge experiments with multiple
      addition of WNV at maximal load (approx. 105 CFU/ml) and repeated illumination
      without replenishing MB were performed. RESULTS: Complete inactivation of WNV was
      achieved by MB (0.8-1 mmol/l) and illumination with white light (30,000-45,000
      Lux) within 2 min. White yellow light 20-40 J/cm(2) (2.5-5 min) were sufficient
      for inactivation by 5.75 log10-steps. The rechallenge experiments revealed the
      substantial reserve capacity of the procedure to inactivate WNV. Quantitative PCR
      indicated that the viral RNA was rapidly destroyed. CONCLUSION: All experimental
      data demonstrate the enormous potency of phototreatment with MB to inactivate WNV
      in plasma.

PMID- 15157257
TI  - Decreased platelet aggregation of platelet concentrate during storage recovers in
      the body after transfusion.
AB  - BACKGROUND: Previous reports have shown that storage decrease the ability of PLTs
      to aggregate in the form of PLT concentrate (PC). Nevertheless, there are few
      reports that have studied the PLT function in blood samples obtained from
      recipients after PLT transfusion. In this study, this issue was addressed by
      examining the ability of PLTs to aggregate after being transfused into the blood
      stream. STUDY DESIGN AND METHODS: PC was transfused to the patients with
      extremely low PLT counts resulting from chemotherapy. The maximum extent of PLT
      aggregation and size of the aggregates were compared between PLT in stored PC
      before transfusion with the PLT-rich plasma (PRP) from the recipients after
      transfusion and with PRP from patients with moderate decrease in PLT counts after
      chemotherapy. RESULTS: The maximum extent of PLT aggregation was significantly
      higher in PRP collected from the patients after transfusion compared to the
      extent obtained before transfusion. There were no significant differences in the
      maximum extents of PLT aggregation between the PRP collected from the recipients
      after PC transfusion and, in the same patients, when PLT counts were moderately
      low. CONCLUSION: These results suggest that the observed decreased in PLT
      aggregation after storage can improve in the body after transfusion, and
      transfused PLTs have similar aggregation ability compared to the PLTs derived
      from the patient.

PMID- 15157259
TI  - Patient care during infusion of hematopoietic progenitor cells.

PMID- 15157260
TI  - Collection of white blood cell-reduced plasma by apheresis.
AB  - BACKGROUND: WBC reduction of cellular blood components has been introduced in
      many countries. Owing to concerns of residual WBCs in plasma, a new method to
      collect WBC-reduced plasma by apheresis was studied. STUDY DESIGN AND METHODS: An
      apheresis machine (PCS2, Haemonetics) was used, in combination with the "high
      separation" core (HSC) bowl, a redesigned version of the blow-molded (BM) bowl.
      With the BM bowl collections as control group, various software settings were
      investigated applying the HSC bowl. The optimized program was validated for
      routine application. Results are expressed as means +/- SD. RESULTS: Plasma
      collected in the control group with the BM bowl (n = 25) had a volume of 622 +/-
      7 mL and contained 5.3 +/- 4.6 x 10(6) WBCs per L, 11 +/- 5 x 10(9) PLTs per L,
      and 0.063 +/- 0.051 x 10(9) RBCs per L. The collection efficiency was 17.8 +/-
      2.8 mL per minute, and the total procedure time was 36.1 +/- 6.3 minutes. The HSC
      bowl produced plasma that had a volume of 623 +/- 9 mL and contained 0.01 +/-
      0.02 x 10(6) WBCs per L, 2 +/- 2 x 10(9) PLTs per L, and 0.00040 +/- 0.0016 x
      10(9) RBCs per L (n = 134, all p < 0.001). The collection efficiency was 15.8 +/-
      2.2 mL per minute, and the collection time was 40.3 +/- 6.3 minutes (both p <
      0.001). CONCLUSION: The HSC bowl with the new software reliably produces WBC
      reduced apheresis plasma, with a slight elongation of the procedure time.

PMID- 15157258
TI  - A new automated cell washer device for thawed cord blood units.
AB  - BACKGROUND: The current available techniques to wash out DMSO from thawed
      umbilical cord blood (UCB) units are based essentially on standard centrifugation
      in an open system with various degrees of cell loss. STUDY DESIGN AND METHODS: We
      evaluated the capacity of a new automated closed device (Cytomate, Baxter, IL) to
      wash out the DMSO from thawed UCB units, saving at the same time the progenitor
      and accessory cells in terms of CD34+ cells and MNCs. We modified the standard
      software of the device and calculated the cell recovery on 25 UCB units.
      Moreover, we set up a new gas chromatographic method to exactly detect the DMSO
      removal rate. RESULTS: To evaluate the efficiency of the Cytomate device, we
      considered the postthawing (prewashing) versus postwashing cell recovery. The
      average recovery (%) in terms of total nucleated cells was 63.30 (range, 40.12
      89.00), CD34+ cells was 70.20 (range, 11.51-89.01), CD3+ cells was 61.01 (range,
      28.80-87.08), CD4+ cells was 62.53 (range, 30.62-96.73), CD8+ cells was 57.4
      (range, 26.87-94.72), CD19+ cells was 63.33 (range, 39.10-90.33), CD16+/56+ cells
      was 70.67 (range, 8.91-98.40), CFU-GM was 74.33 (range, 20.23-98.60), total CFUs
      was 82.34 (range, 14.83-247.12), and viability was 89.67(range, 70.74-98.30). The
      total working time required was, on average, 15 minutes (range, 7-20).
      CONCLUSIONS: The Cytomate device demonstrated a satisfying efficiency in cell
      recovery and in maintaining the clonogenic power of the UCB graft. The removal
      rate of DMSO was practically complete with evident advantages for the recipient.
      Finally, the entire manipulation performed in a closed system revealed to be
      safe, maintaining the sterility of the graft.

PMID- 15157261
TI  - Predonation water ingestion attenuates negative reactions to blood donation.
AB  - BACKGROUND: Novice blood donors are at increased risk for unpleasant blood
      donation-related symptoms (e.g., dizziness, weakness, and lightheadedness), and
      the experience of such symptoms can contribute to a decreased likelihood of
      repeat donation. Recent laboratory studies suggest that water ingestion produces
      hemodynamic effects that may be sufficient to reduce risk of syncope and related
      reactions during blood donation. STUDY DESIGN AND METHODS: Male and female
      volunteers were randomly assigned to ingest either 500 or 0 mL of water 30
      minutes before donating blood for the first time. In addition, bioimpedance
      analysis was used to assess predonation chronic hydration levels in all donors.
      Immediately after donation, participants completed the Blood Donation Reactions
      Inventory to assess subjective experience of negative physiologic reactions.
      RESULTS: Analysis of Blood Donation Reactions Inventory scores revealed that
      predonation water ingestion was associated with a 47-percent reduction of total
      donation-related symptoms (F [1,79]= 11.81, p = 0.001). Chronic hydration status
      was not related to reported reactions. CONCLUSION: Novice blood donors responded
      positively to predonation water consumption, and they were able to consume 500 mL
      in less than 5 minutes. Results of the present study suggests that predonation
      water ingestion may be a simple and cost-effective strategy to enhance the
      donation experience and possibly increase donor retention.

PMID- 15157262
TI  - Window-period human immunodeficiency virus transmission to two recipients by an
      adolescent blood donor.
AB  - BACKGROUND: Pooled NAT and donor screening have reduced the diagnostic window
      period for HIV in the blood donor population to approximately 10 to 15 days. This
      report describes two cases of transfusion-acquired HIV infection and verification
      of transmission from the donor to the recipients, and attempts to identify how
      the 18-year-old donor acquired her infection. STUDY DESIGN AND METHODS: After a
      repeat donor had a positive HIV test result, two recipients of the donor's
      previous donation were identified and tested. The donor and recipients were
      interviewed and blood samples were obtained for HIV DNA sequencing and
      phylogenetic analysis. RESULTS: The two recipients had positive HIV test results.
      Phylogenetic analysis showed a high genetic similarity among the viruses
      (bootstrap 100%), consistent with transmission from the donor to the recipients.
      Four of five men with whom the donor had sexual contact during the critical time
      period when infection most likely occurred were located and tested; results were
      negative for HIV. CONCLUSIONS: Pooled NAT of blood donations has not eliminated
      the window period for HIV identification during seroconversion.

PMID- 15157265
TI  - Hepatitis B virus-infected peripheral blood progenitor cell harvests in liquid
      nitrogen freezer containing non-infectious products.

PMID- 15157263
TI  - Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E
      virus strain in Hokkaido, Japan.
AB  - BACKGROUND: In industrialized countries, sporadic cases of hepatitis E have been
      reported in individuals who have never been in an endemic area. Hepatitis E virus
      (HEV) infection commonly occurs via the fecal-oral route but a potential risk of
      transfusion transmission route has been suggested. STUDY DESIGN AND METHODS: A 67
      year-old Japanese male patient who had never been abroad received a transfusion
      of blood from 23 voluntary donors and developed acute hepatitis with unknown
      etiology after transfusion. His blood samples were tested for viral markers of
      hepatitis viruses. RESULTS: HAV, HBV, HCV, CMV, and EBV were ruled out as
      causative agents in this case. The patient's blood sample in the acute phase
      contained HEV RNA as well as IgM and IgG anti-HEV. HEV RNA was also detected in
      one of the FFP units transfused. The donor had no history of traveling abroad and
      had a normal ALT level at the time of donation. The PCR products from the patient
      and the donor showed complete identity for two distinct regions of HEV within
      open reading frame 1. CONCLUSION: The patient was infected with HEV via
      transfused blood from a volunteer donor. A potential risk of posttransfusion
      hepatitis E should be considered even in nonendemic countries.

PMID- 15157266
TI  - ABO genotyping by minisequencing analysis.

PMID- 15157267
TI  - Platelet-derived growth factor-AB and transforming growth factor-beta 1 in
      platelet gels activated by single-donor human thrombin.

PMID- 15157268
TI  - Late-onset pure red blood cell aplasia owing to delayed lymphoid engraftment
      complicating ABO-mismatched hematopoietic stem cell transplantation.

PMID- 15157269
TI  - Acute hyperphosphatemia after plasma exchange with S/D-treated plasma.

PMID- 15157270
TI  - Methylene-blue-photoinactivated plasma and its contribution to blood safety.

PMID- 15157272
TI  - Vasectomy surgical techniques: a systematic review.
AB  - BACKGROUND: A wide variety of surgical techniques are used to perform vasectomy.
      The purpose of this systematic review was to assess if any surgical techniques to
      isolate or occlude the vas are associated with better outcomes in terms of
      occlusive and contraceptive effectiveness, and complications. METHODS: We
      searched MEDLINE (1966-June 2003), EMBASE (1980-June 2003), reference lists of
      retrieved articles, urology textbooks, and our own files looking for studies
      comparing two or more vasectomy surgical techniques and reporting on
      effectiveness and complications. From 2,058 titles or abstracts, two independent
      reviewers identified 224 as potentially relevant. Full reports of 219 articles
      were retrieved and final selection was made by the same two independent reviewers
      using the same criteria as for the initial selection. Discrepancies were resolved
      by involving a third reviewer. Data were extracted and methodological quality of
      selected studies was assessed by two independent reviewers. Studies were divided
      in broad categories (isolation, occlusion, and combined isolation and occlusion
      techniques) and sub-categories of specific surgical techniques performed.
      Qualitative analyses and syntheses were done. RESULTS: Of 31 comparative studies
      (37 articles), only four were randomized clinical trials, most studies were
      observational and retrospective. Overall methodological quality was low. From
      nine studies on vas isolation, there is good evidence that the no-scalpel
      vasectomy approach decreases the risk of surgical complications, namely
      hematoma/bleeding and infection, compared with incisional techniques. Five
      comparative studies including one high quality randomized clinical trial provided
      good evidence that fascial interposition (FI) increases the occlusive
      effectiveness of ligation and excision. Results of 11 comparative studies suggest
      that FI with cautery of the vas lumen provides the highest level of occlusive
      effectiveness, even when leaving the testicular end open. Otherwise, firm
      evidence to support any occlusion technique in terms of increased effectiveness
      or decreased risk of complications is lacking. CONCLUSIONS: Current evidence
      supports no-scalpel vasectomy as the safest surgical approach to isolate the vas
      when performing vasectomy. Adding FI increases effectiveness beyond ligation and
      excision alone. Occlusive effectiveness appears to be further improved by
      combining FI with cautery. Methodologically sound prospective controlled studies
      should be conducted to evaluate specific occlusion techniques further.

PMID- 15157273
TI  - Socioeconomic disparities in intimate partner violence against Native American
      women: a cross-sectional study.
AB  - BACKGROUND: Intimate partner violence (IPV) against women is a global public
      health problem, yet data on IPV against Native American women are extremely
      limited. We conducted a cross-sectional study of Native American women to
      determine prevalence of lifetime and past-year IPV and partner injury; examine
      IPV in relation to pregnancy; and assess demographic and socioeconomic correlates
      of past-year IPV. METHODS: Participants were recruited from a tribally-operated
      clinic serving low-income pregnant and childbearing women in southwest Oklahoma.
      A self-administered survey was completed by 312 Native American women (96%
      response rate) attending the clinic from June through August 1997. Lifetime and
      past-year IPV were measured using modified 18-item Conflict Tactics Scales. A
      socioeconomic index was created based on partner's education, public assistance
      receipt, and poverty level. RESULTS: More than half (58.7%) of participants
      reported lifetime physical and/or sexual IPV; 39.1% experienced severe physical
      IPV; 12.2% reported partner-forced sexual activity; and 40.1% reported lifetime
      partner-perpetrated injuries. A total of 273 women had a spouse or boyfriend
      during the previous 12 months (although all participants were Native American,
      59.0% of partners were non-Native). Among these women, past-year prevalence was
      30.1% for physical and/or sexual IPV; 15.8% for severe physical IPV; 3.3% for
      forced partner-perpetrated sexual activity; and 16.4% for intimate partner
      injury. Reported IPV prevalence during pregnancy was 9.3%. Pregnancy was not
      associated with past-year IPV (odds ratio = 0.9). Past-year IPV prevalence was
      42.8% among women scoring low on the socioeconomic index, compared with 10.1%
      among the reference group. After adjusting for age, relationship status, and
      household size, low socioeconomic index remained strongly associated with past
      year IPV (odds ratio = 5.0; 95% confidence interval: 2.4, 10.7). CONCLUSIONS:
      Native American women in our sample experienced exceptionally high rates of
      lifetime and past-year IPV. Additionally, within this low-income sample, there
      was strong evidence of socioeconomic variability in IPV. Further research should
      determine prevalence of IPV against Native American women from diverse tribes and
      regions, and examine pathways through which socioeconomic disadvantage may
      increase their IPV risk.

PMID- 15157274
TI  - The functional organization of mitochondrial genomes in human cells.
AB  - BACKGROUND: We analyzed the organization and function of mitochondrial DNA in a
      stable human cell line (ECV304, which is also known as T-24) containing
      mitochondria tagged with the yellow fluorescent protein. RESULTS: Mitochondrial
      DNA is organized in approximately 475 discrete foci containing 6-10 genomes.
      These foci (nucleoids) are tethered directly or indirectly through mitochondrial
      membranes to kinesin, marked by KIF5B, and microtubules in the surrounding
      cytoplasm. In living cells, foci have an apparent diffusion constant of 1.1 x 10(
      3) microm2/s, and mitochondria always split next to a focus to distribute all DNA
      to one daughter. The kinetics of replication and transcription (monitored by
      immunolabelling after incorporating bromodeoxyuridine or bromouridine) reveal
      that each genome replicates independently of others in a focus, and that newly
      made RNA remains in a focus (residence half-time approximately 43 min) long after
      it has been made. This mitochondrial RNA colocalizes with components of the
      cytoplasmic machinery that makes and imports nuclear-encoded proteins - that is,
      a ribosomal protein (S6), a nascent peptide associated protein (NAC), and the
      translocase in the outer membrane (Tom22). CONCLUSIONS: The results suggest that
      clusters of mitochondrial genomes organize the translation machineries on both
      sides of the mitochondrial membranes. Then, proteins encoded by the nuclear
      genome and destined for the mitochondria will be made close to mitochondrial
      encoded proteins so that they can be assembled efficiently into mitochondrial
      complexes.

PMID- 15157275
TI  - Correlation between thyroid hormone status and hepatic hyperplasia and
      hypertrophy caused by the peroxisome proliferator-activated receptor alpha
      agonist Wy-14,643.
AB  - BACKGROUND: The metabolic inhibitor rotenone inhibits hepatocellular
      proliferation and the incidence of liver cancer resulting from exposure to the
      PPARalpha agonist Wy-14,643, via unknown mechanisms. Since the absence of thyroid
      hormones diminishes hepatomegaly, an early biomarker for the
      hepatocarcinogenicity induced by PPARalpha agonists, this study was undertaken to
      investigate whether rotenone might interference with the ability of Wy-14,643 to
      alter the animal thyroid status. METHODS: Male B6C3F1 mice were given Wy-14,643
      (100 ppm), rotenone (600 ppm) or a mixture of both, in the feed for 7 days.
      Bromodeoxyuridine (BrDU), marker of cell replication, was delivered through
      subcutaneously implanted osmotic mini-pumps. At the end of the experiment, sera
      were collected and corticosterone and thyroid hormone levels were measured by
      solid-phase radioimmunoassay kits. In addition, liver tissue samples were stained
      immunohistochemically for BrDU to determine percentages of labeled cells.
      Further, cell surface area was determined from images generated by a Zeiss
      Axioplan microscope equipped with a plan Neofluar x40 0.75 na objective. Tracings
      of individual hepatocyte perimeters were then analyzed and cell-surface areas
      were calculated using MicroMeasure FL-4000. RESULTS: Wy-14,643 caused a
      significant increase in liver weights, hepatocyte BrDU labeling index (LI), and
      hepatocyte surface area. In animals which received both Wy-14,643 and rotenone
      simultaneously, all of these effects were significantly less pronounced compared
      with mice that received Wy-14,643 alone. Rotenone alone decreased liver weights,
      LI and surface area. The Free Thyroid Index (FTI), which provides an accurate
      reflection of the animal's thyroid status, was 5.0 +/- 0.3 in control mice. In
      animals exposed to rotenone, these values decreased to 2.0 +/- 0.9, but in
      animals which received Wy-14,643, levels increased significantly to 7.7 +/- 0.9.
      FTI values decreased to 3.4 +/- 0.8 in mice receiving both rotenone and Wy
      14,643. CONCLUSION: A strong correlation was observed between the animal thyroid
      status and both, hepatocyte proliferation (r2 = 0.62), and hepatocyte surface
      area (r2 = 0.83). These results support the hypothesis that the thyroid status of
      the animal plays a role in PPARalpha-induced hepatocellular proliferation and
      liver cell enlargement. Both these events are known to contribute to the
      expression of liver cancer in response to the activation of PPARalpha.

PMID- 15157276
TI  - APOAV (T-1131>C) variant has no effect on mother's height in a large population
      study.
AB  - The important role of APOAV gene T-1131>C variant in determination of plasma
      triglyceride levels has been proved on many population studies. Recently,
      associations between C-1131 allele and higher mother's height as well as with
      longer fetal birth length were suggested. In 1,305 females, aged between 28 and
      67 years and having at least one child, we have analyzed a putative association
      between T-1131>C APOAV variant (analyzed by PCR and restriction analysis) and
      body height. Mother's body height did not differ between T/T homozygotes (N =
      1093, 162.5 +/- 6.5 cm) and C allele carriers (N = 212, 162.1 +/- 6.4 cm). Thus
      we have failed to confirm, that mothers with APOAV C-1131 allele are higher than
      T/T-1131 homozygotes.

PMID- 15157279
TI  - Description and validation of a Markov model of survival for individuals free of
      cardiovascular disease that uses Framingham risk factors.
AB  - BACKGROUND: Estimation of cardiovascular disease risk is increasingly used to
      inform decisions on interventions, such as the use of antihypertensives and
      statins, or to communicate the risks of smoking. Crude 10-year cardiovascular
      disease risk risks may not give a realistic view of the likely impact of an
      intervention over a lifetime and will underestimate of the risks of smoking. A
      validated model of survival to act as a decision aid in the consultation may help
      to address these problems. This study aims to describe the development of such a
      model for use with people free of cardiovascular disease and evaluates its
      accuracy against data from a United Kingdom cohort. METHODS: A Markov cycle tree
      evaluated using cohort simulation was developed utilizing Framingham estimates of
      cardiovascular risk, 1998 United Kingdom mortality data, the relative risk for
      smoking related non-cardiovascular disease risk and changes in systolic blood
      pressure and serum total cholesterol total cholesterol with age. The model's
      estimates of survival at 20 years for 1391 members of the Whickham survey cohort
      between the ages of 35 and 65 were compared with the observed survival at 20-year
      follow-up. RESULTS: The model estimate for survival was 75% and the observed
      survival was 75.4%. The correlation between estimated and observed survival was
      0.933 over 39 subgroups of the cohort stratified by estimated survival, 0.992 for
      the seven 5-year age bands from 35 to 64, 0.936 for the ten 10 mmHg systolic
      blood pressure bands between 100 mmHg and 200 mmHg, and 0.693 for the fifteen 0.5
      mmol/l total cholesterol bands between 3.0 and 10.0 mmol/l. The model
      significantly underestimated mortality in those people with a systolic blood
      pressure greater than or equal to 180 mmHg (p = 0.006). The average gain in life
      expectancy from the elimination of cardiovascular disease risk as a cause of
      death was 4.0 years for all the 35 year-old men in the sample (n = 24), and 1.8
      years for all the 35 year-old women in the sample (n = 32). CONCLUSIONS: This
      model accurately estimates 20-year survival in subjects from the Whickham cohort
      with a systolic blood pressure below 180 mmHg.

PMID- 15157278
TI  - Assessing the impact of heart failure specialist services on patient populations.
AB  - BACKGROUND: The assessment of the impact of healthcare interventions may help
      commissioners of healthcare services to make optimal decisions. This can be
      particularly the case if the impact assessment relates to specific patient
      populations and uses timely local data. We examined the potential impact on
      readmissions and mortality of specialist heart failure services capable of
      delivering treatments such as b-blockers and Nurse-Led Educational Intervention
      (N-LEI). METHODS: Statistical modelling of prevented or postponed events among
      previously hospitalised patients, using estimates of: treatment uptake and
      contraindications (based on local audit data); treatment effectiveness and
      intolerance (based on literature); and annual number of hospitalization per
      patient and annual risk of death (based on routine data). RESULTS: Optimal
      treatment uptake among eligible but untreated patients would over one year
      prevent or postpone 11% of all expected readmissions and 18% of all expected
      deaths for spironolactone, 13% of all expected readmisisons and 22% of all
      expected deaths for b-blockers (carvedilol) and 20% of all expected readmissions
      and an uncertain number of deaths for N-LEI. Optimal combined treatment uptake
      for all three interventions during one year among all eligible but untreated
      patients would prevent or postpone 37% of all expected readmissions and a minimum
      of 36% of all expected deaths. CONCLUSION: In a population of previously
      hospitalised patients with low previous uptake of b-blockers and no uptake of N
      LEI, optimal combined uptake of interventions through specialist heart failure
      services can potentially help prevent or postpone approximately four times as
      many readmissions and a minimum of twice as many deaths compared with simply
      optimising uptake of spironolactone (not necessarily requiring specialist
      services). Examination of the impact of different heart failure interventions can
      inform rational planning of relevant healthcare services.

PMID- 15157280
TI  - Prediction of chronic disability in work-related musculoskeletal disorders: a
      prospective, population-based study.
AB  - BACKGROUND: Disability associated with work-related musculoskeletal disorders is
      an increasingly serious societal problem. Although most injured workers return
      quickly to work, a substantial number do not. The costs of chronic disability to
      the injured worker, his or her family, employers, and society are enormous. A
      means of accurate early identification of injured workers at risk for chronic
      disability could enable these individuals to be targeted for early intervention
      to promote return to work and normal functioning. The purpose of this study is to
      develop statistical models that accurately predict chronic work disability from
      data obtained from administrative databases and worker interviews soon after a
      work injury. Based on these models, we will develop a brief instrument that could
      be administered in medical or workers' compensation settings to screen injured
      workers for chronic disability risk. METHODS: This is a population-based,
      prospective study. The study population consists of workers who file claims for
      work-related back injuries or carpal tunnel syndrome (CTS) in Washington State.
      The Washington State Department of Labor and Industries claims database is
      reviewed weekly to identify workers with new claims for work-related back
      injuries and CTS, and these workers are telephoned and invited to participate.
      Workers who enroll complete a computer-assisted telephone interview at baseline
      and one year later. The baseline interview assesses sociodemographic, employment
      related, biomedical/health care, legal, and psychosocial risk factors. The follow
      up interview assesses pain, disability, and work status. The primary outcome is
      duration of work disability over the year after claim submission, as assessed by
      administrative data. Secondary outcomes include work disability status at one
      year, as assessed by both self-report and work disability compensation status
      (administrative records). A sample size of 1,800 workers with back injuries and
      1,200 with CTS will provide adequate statistical power (0.96 for low back and
      0.85 for CTS) to predict disability with an alpha of.05 (two-sided) and a hazard
      ratio of 1.2. Proportional hazards regression models will be constructed to
      determine the best combination of predictors of work disability duration at one
      year. Regression models will also be developed for the secondary outcomes.

PMID- 15157277
TI  - DNA and the chromosome - varied targets for chemotherapy.
AB  - The nucleus of the cell serves to maintain, regulate, and replicate the critical
      genetic information encoded by the genome. Genomic DNA is highly associated with
      proteins that enable simple nuclear structures such as nucleosomes to form higher
      order organisation such as chromatin fibres. The temporal association of
      regulatory proteins with DNA creates a dynamic environment capable of quickly
      responding to cellular requirements and distress. The response is often mediated
      through alterations in the chromatin structure, resulting in changed
      accessibility of specific DNA sequences that are then recognized by specific
      proteins. Anti-cancer drugs that target cellular DNA have been used clinically
      for over four decades, but it is only recently that nuclease specific drugs have
      been developed to not only target the DNA but also other components of the
      nuclear structure and its regulation. In this review, we discuss some of the new
      drugs aimed at primary DNA sequences, DNA secondary structures, and associated
      proteins, keeping in mind that these agents are not only important from a
      clinical perspective but also as tools for understanding the nuclear environment
      in normal and cancer cells.

PMID- 15157281
TI  - Knowledge and attitude towards HIV/AIDS among Iranian students.
AB  - BACKGROUND: Young people are of particular importance in state policies against
      Acquired Immunodeficiency Syndrome (AIDS). We intended to assess the knowledge
      and attitude of high school students regarding AIDS in Iran. METHODS: Through a
      cluster-sampling, 4641 students from 52 high schools in Tehran were assessed by
      anonymous questionnaires in February 2002. RESULTS: The students identified
      television as their most important source of information about AIDS. Only a few
      students answered all the knowledge questions correctly, and there were many
      misconceptions about the routes of transmission. Mosquito bites (33%), public
      swimming pools (21%), and public toilets (20%) were incorrectly identified as
      routes of transmission. 46% believed that Human Immunodeficiency Virus positive
      (HIV positive) students should not attend ordinary schools. Most of the students
      wanted to know more about AIDS. In this study knowledge level was associated with
      students' attitudes and discipline (p < 0.001). CONCLUSION: Although the
      knowledge level seems to be moderately high, misconceptions about the routes of
      transmission were common. There was a substantial intolerant attitude towards
      AIDS and HIV positive patients. We recommend that strategies for AIDS risk
      reduction in adolescents be developed in Iranian high schools.

PMID- 15157282
TI  - Resistance to gemcitabine in a human follicular lymphoma cell line is due to
      partial deletion of the deoxycytidine kinase gene.
AB  - BACKGROUND: Gemcitabine is an analogue of deoxycytidine with activity against
      several solid tumors. In order to elucidate the mechanisms by which tumor cells
      become resistant to gemcitabine, we developed the resistant subline RL-G from the
      human follicular lymphoma cell line RL-7 by prolonged exposure of parental cells
      to increasing concentrations of gemcitabine. RESULTS: In vitro, the IC50
      increased from 0.015 microM in parental RL-7 cells to 25 microM in the resistant
      variant, RL-G. Xenografts of both cell lines developed in nude mice were treated
      with repeated injections of gemcitabine. Under conditions of gemcitabine
      treatment which totally inhibited the development of RL-7 tumors, RL-G derived
      tumors grew similarly to those of untreated animals, demonstrating the in vivo
      resistance of RL-G cells to gemcitabine. HPLC experiments showed that RL-G cells
      accumulated and incorporated less gemcitabine metabolites into DNA and RNA than
      RL-7 cells. Gemcitabine induced an S-phase arrest in RL-7 cells but not in RL-G
      cells. Exposure to gemcitabine induced a higher degree of apoptosis in RL-7 than
      in RL-G cells, with poly-(ADP-ribose) polymerase cleavage in RL-7 cells. No
      modifications of Bcl-2 nor of Bax expression were observed in RL-7 or RL-G cells
      exposed to gemcitabine. These alterations were associated with the absence of the
      deoxycytidine kinase mRNA expression observed by quantitative RT-PCR in RL-G
      cells. PCR amplification of desoxycytidine kinase gene exons showed a partial
      deletion of the dCK gene in RL-G cells. CONCLUSIONS: These results suggest that
      partial deletion of the dCK gene observed after selection in the presence of
      gemcitabine is involved with resistance to this agent both in vitro and in vivo.

PMID- 15157283
TI  - Lithium facilitates apoptotic signaling induced by activation of the Fas death
      domain-containing receptor.
AB  - BACKGROUND: Lithium, a mood stabilizer widely used to treat bipolar disorder,
      also is a neuroprotectant, providing neurons protection from apoptosis induced by
      a broad spectrum of toxic conditions. A portion of this neuroprotection is due to
      lithium's inhibition of glycogen synthase kinase-3. The present investigation
      examined if the neuroprotection provided by lithium included apoptosis induced by
      stimulation of the death domain-containing receptor Fas. RESULTS: Instead of
      providing protection, treatment with 20 mM lithium significantly increased
      apoptotic signaling induced by activation of Fas, and this occurred in both
      Jurkat cells and differentiated immortalized hippocampal neurons. Other
      inhibitors of glycogen synthase kinase-3, including 20 microM indirubin-3'
      monoxime, 5 microM kenpaullone, and 5 microM rottlerin, also facilitated Fas
      induced apoptotic signaling, indicating that the facilitation of apoptosis by
      lithium was due to inhibition of glycogen synthase kinase-3. CONCLUSIONS: These
      results demonstrate that lithium is not always a neuroprotectant, and it has the
      opposite effect of facilitating apoptosis mediated by stimulation of death domain
      containing receptors.

PMID- 15157284
TI  - Patterns of linkage disequilibrium and haplotype distribution in disease
      candidate genes.
AB  - BACKGROUND: The adequacy of association studies for complex diseases depends
      critically on the existence of linkage disequilibrium (LD) between functional
      alleles and surrounding SNP markers. RESULTS: We examined the patterns of LD and
      haplotype distribution in eight candidate genes for osteoporosis and/or obesity
      using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE),
      type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin
      receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1
      (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3
      (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang
      haplotypes, two high-frequency haplotypes composed of completely mismatching SNP
      alleles, were examined. To quantify LD patterns, two common measures of LD, D'
      and r2, were calculated for the SNPs within the genes. The haplotype distribution
      varied in the different genes. Yin yang haplotypes were observed only in PTHR1
      and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the
      average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as
      the intermarker distance increased, however, there was a great difference in LD
      characteristics of different genes or even in different regions within gene.
      CONCLUSION: The differences in haplotype distributions and LD patterns among the
      genes underscore the importance of characterizing genomic regions of interest
      prior to association studies.

PMID- 15157286
TI  - Evolution of the brain: from behavior to consciousness in 3.4 billion years.
AB  - Once life began as single-cell organisms, evolution favored those able to seek
      nutrients and avoid risks. Receptors sensed the environment, memory traces were
      laid, and adaptive responses were made. Environmental stress, at times as
      dramatic as the collision of an asteroid, resulted in extinctions that favored
      small predators with dorsal nerve cords and cranially positioned brains.
      Myelination, and later thermoregulation, led to increasingly efficient neural
      processing. As somatosensory, visual, and auditory input increased, a neocortex
      developed containing both sensory and motor neural maps. Hominids, with their
      free hands, pushed cortical development further and began to make simple stone
      tools. Tools and increasing cognition allowed procurement of a richer diet that
      led to a smaller gut, thus freeing more energy for brain expansion. Multimodal
      association areas, initially developed for processing incoming sensory
      information, blossomed and began to provide the organism with an awareness of
      self and environment. Advancements in memory storage and retrieval gave the
      organism a sense of continuity through time. This developing consciousness
      eventually left visible traces, which today are dramatically evident on cave
      walls in France and Spain. We will take this journey from the single cell to
      human consciousness.

PMID- 15157285
TI  - Cytochalasin B triggers a novel pertussis toxin sensitive pathway in TNF-alpha
      primed neutrophils.
AB  - BACKGROUND: Cytochalasin B does not directly activate the oxygen-radical
      producing NADPH oxidase activity of neutrophils but transfers desensitized G
      protein coupled receptors (GPCR) into an active signaling state by uncoupling
      GCPR from the cytoskeleton. The receptor uncoupling results in respiratory burst
      activity when signals generated by reactivated formyl peptide receptors trigger
      the NADPH-oxidase to produce superoxide anions. RESULTS: Tumor necrosis factor
      alpha (TNF-alpha) primes neutrophils for subsequent activation by cytochalasin B.
      Pretreatment with TNF-alpha induced mobilization of receptor-storing neutrophil
      organelles, suggesting that receptor up-regulation significantly contributes to
      the response, but the receptor mobilization was not sufficient for induction of
      the cytochalasin B sensitive state. The TNF-alpha primed state resembled that of
      the desensitized non-signaling state of agonist-occupied neutrophil formyl
      peptide receptors. The fact that the TNF-alpha primed, cytochalasin B-triggered
      activation process was pertussis toxin sensitive suggests that the activation
      process involves a GPCR. Based on desensitization experiments the unidentified
      receptor was found to be distinct from the C5a receptor as well as the formyl
      peptide receptor family members FPR and FPRL1. Based on the fact the occupied and
      desensitized receptors for interleukin-8 and platelet activating factor could not
      be reactivated by cytochalasin B, also these could be excluded as receptor
      candidates involved in the TNF-alpha primed state. CONCLUSIONS: The TNF-alpha
      induced priming signals could possibly trigger a release of an endogenous GPCR
      agonist, amplifying the response to the receptor-uncoupling effect of
      cytochalasin B. However, no such substance could be found, suggesting that TNF
      alpha can transfer G-protein coupled receptors to a signaling state independently
      of agonist binding.

PMID- 15157287
TI  - A neuroforensic analysis of the wounds of President John F. Kennedy: Part 2--A
      study of the available evidence, eyewitness correlations, analysis, and
      conclusions.
AB  - A substantial body of literature exists surrounding the assassination and
      subsequent pathological examination of President John F. Kennedy. In the first
      part of this series, we provided a previously undocumented eyewitness account by
      a neurosurgeon of what transpired in Trauma Room 1 of Parkland Memorial Hospital
      on November 22, 1963. The current article reviews the copious literature and
      extensive controversy regarding President Kennedy's wounds. The autopsy report,
      ballistics data, official reviews of the autopsy data, and Dr. Grossman's
      observations are correlated in an effort to provide a neuroforensic analysis of
      the nature of the wounds that President Kennedy sustained. The final article of
      the series will relate the wounds to the timing of the shots and the location of
      the President as his limousine traversed Dealey Plaza and will discuss the sites
      from which the bullets could have been fired.

PMID- 15157288
TI  - Microsurgical approaches to the perimesencephalic cisterns and related segments
      of the posterior cerebral artery: comparison using a novel application of image
      guidance.
AB  - OBJECTIVE: To describe the exposure obtained through six approaches to the
      perimesencephalic cisterns with an emphasis on exposure of the posterior cerebral
      artery and its branches. METHODS: Dissections in 12 hemispheres exposed the
      crural, ambient, and quadrigeminal cisterns and related segments of the posterior
      cerebral artery. A Stealth Image Guidance workstation (Medtronic Surgical
      Navigation Technologies, Louisville, CO) was used to compare the approaches.
      RESULTS: The transsylvian approach exposed the interpeduncular and crural
      cisterns. The subtemporal approach exposed the interpeduncular and crural
      cisterns as well as the lower half of the ambient cistern. Temporal lobe
      retraction and the position of the vein of Labbe limited exposure of the
      quadrigeminal cistern. Occipital transtentorial and infratentorial
      supracerebellar approaches exposed the quadrigeminal and lower two-thirds of the
      ambient cistern. Transchoroidal approaches exposed the posterior third of the
      crural cistern, the upper two-thirds of the ambient cistern, and the proximal
      quadrigeminal cistern. Transchoroidal approaches exposed the posterior portion of
      the P2 segment (P2p) in 9 of 10 hemispheres and were the only approaches that
      exposed the lateral posterior choroidal arteries and the plexal segment of the
      anterior choroidal artery. Occipital transtentorial and infratentorial
      supracerebellar approaches provided access to the P3 segment in all cases and
      exposed the P2p segment in 4 of 10 hemispheres. The subtemporal approach provided
      access to the cisternal and crural segments of the anterior choroidal and medial
      posterior choroidal arteries and exposed the P2p segment in 3 of 10 hemispheres.
      CONCLUSION: Surgical approaches to lesions of the perimesencephalic cisterns must
      be tailored to the site of the pathological findings. The most challenging area
      to expose is the upper half of the ambient cistern, particularly the P2p segment
      of the posterior cerebral artery.

PMID- 15157289
TI  - Results of a prospective protocol of computed tomographic angiography in place of
      catheter angiography as the only diagnostic and pretreatment planning study for
      cerebral aneurysms by a combined neurovascular team.
AB  - OBJECTIVE: At many centers, patients undergo both computed tomographic
      angiography (CTA) and digital subtraction angiography (DSA). This practice
      negates most of the advantages of CTA, and it renders the risks and disadvantages
      of the two techniques additive. Previous reports in the literature have assessed
      the sensitivity and specificity of CTA compared with DSA; however, these
      investigations have not analyzed the clinical implications of a protocol that
      replaces DSA with CTA as the only diagnostic and pretreatment planning study for
      patients with cerebral aneurysms. METHODS: Since late 2001/early 2002, the
      combined neurovascular unit of the Massachusetts General Hospital has adopted a
      prospective protocol of CTA in place of DSA as the only diagnostic and
      pretreatment planning study for patients with cerebral aneurysms (ruptured and
      unruptured). We report the results obtained during the 12-month period from
      January 2002 to January 2003. RESULTS: During the study period, 223 patients with
      cerebral aneurysms underwent initial diagnostic evaluation for cerebral aneurysm
      by the combined neurovascular team of Massachusetts General Hospital. Of the 223
      patients, 109 patients had confirmed subarachnoid hemorrhage (Group A) and 114
      patients did not have SAH (Group B). All of these patients were included in the
      prospective CTA protocol. Cerebral aneurysm treatment was initiated on the basis
      of CTA alone in 93 Group A patients (86%), in 89 Group B patients (78%), and in
      182 patients (82%) overall. Treatment consisted of surgical clipping in 152
      patients (68%), endovascular coiling in 56 patients (25%), endovascular parent
      artery balloon occlusion in 4 patients (2%), and external carotid artery to
      internal carotid artery bypass and carotid artery surgical occlusion in 2
      patients (1%). Nine patients (4%) did not undergo treatment. The cerebral
      aneurysm detection rate by CTA was 100% for the presenting aneurysm (ruptured
      aneurysm in Group A or symptomatic/presenting aneurysm in Group B) in both
      groups. The detection rate by CTA for total cerebral aneurysms, including
      incidental multiple aneurysms, was 95.3% in Group A, 98.3% in Group B, and 97%
      overall. The overall morbidity associated with DSA (pretreatment or as
      intraoperative or postoperative clip evaluation) was one patient (1.3%) with a
      minor nonneurological complication, one patient (1.3%) with a minor neurological
      complication, and no patients (0%) with a major neurological complication.
      CONCLUSION: We have demonstrated promising results with a prospective protocol of
      CTA in place of DSA as the only diagnostic and pretreatment planning study for
      patients with ruptured and unruptured cerebral aneurysms. It seems safe and
      effective to make decisions regarding treatment on the basis of CTA, without
      performing DSA, in the majority of patients with ruptured and unruptured cerebral
      aneurysms.

PMID- 15157290
TI  - Is aspect ratio a reliable predictor of intracranial aneurysm rupture?
AB  - OBJECTIVE: This study was undertaken to assess the reliability of the aspect
      ratio (AR) (i.e., aneurysm depth to aneurysm neck) in predicting aneurysm
      rupture. It has been shown that the AR is a key factor in predicting
      intraaneurysmal blood flow and aneurysm rupture. METHODS: Seventy-five patients
      with subarachnoid hemorrhage and multiple aneurysms were studied. The sizes of
      the aneurysms and their ARs were determined by examining the angiographic films.
      By comparing the difference between ruptured and unruptured aneurysms in the same
      individual, each patient in effect served as his or her own control. Each
      ruptured aneurysm was confirmed during surgery. RESULTS: There were 75 ruptured
      and 107 unruptured aneurysms. The mean AR was 2.70 for ruptured aneurysms,
      compared with 1.8 for unruptured aneurysms. This difference between the ARs was
      statistically significant (P < 0.001). The difference in aneurysm sizes in the
      two groups also was significant (P < 0.001). CONCLUSION: AR on its own is as
      reliable a variable as the size of the aneurysm for predicting aneurysm rupture.

PMID- 15157291
TI  - The relationship of coexisting extranidal aneurysms to intracranial hemorrhage in
      patients harboring brain arteriovenous malformations.
AB  - OBJECTIVE: We hypothesized that coexisting extranidal arterial aneurysms (EAs)
      would be associated with an increased risk of incident intracranial hemorrhage
      (ICH) from brain arteriovenous malformation (BAVM) rupture. METHODS: To determine
      the presence of EAs and compare the sources and locations of ICH, we
      retrospectively reviewed the computed tomographic, magnetic resonance imaging,
      and angiographic studies of patients who presented between 1990 and 1999. EAs
      were defined as saccular luminal dilations of the parent feeding vessels that
      were proximally flow-related (i.e., at the circle of Willis), distally flow
      related (i.e., distal to the circle of Willis), and unrelated (i.e., in
      circulation distant from the BAVM). RESULTS: Of 314 BAVM patients, 138 (44%)
      presented with ICH. In the ICH group, 22 patients (16%) had aneurysmal ICH, 100
      (72%) had BAVM ICH, and 16 (12%) had ICH from an indeterminate source. There were
      61 patients with 1 or more EAs (29 patients with 42 flow-related proximal
      aneurysms, 39 patients with 48 flow-related distal aneurysms, and 10 patients
      with 20 unrelated aneurysms). Multivariate regression analysis revealed that ICH
      patients were more likely than non-ICH patients to have a coexisting EA (35
      versus 13%; odds ratio = 3.9; 95% confidence interval, 2.1-7.5; P < 0.001), but
      this effect was not present when only BAVM-related ICH was considered (odds ratio
      = 0.3; 95% confidence interval, 0.1-1.0; P = 0.052). Other independent predictors
      of ICH included small AVM size (<3 cm), exclusively deep venous drainage, and the
      presence of an intranidal aneurysm. CONCLUSION: Clinical presentation with ICH
      was associated with EA aneurysms, but the association was due to aneurysmal
      rather than BAVM rupture, suggesting that EAs and the BAVM ICH risks may be
      considered as separate entities in future studies.

PMID- 15157292
TI  - Endovascular occlusion of wide-necked aneurysms with a new intracranial
      microstent (Neuroform) and detachable coils.
AB  - OBJECTIVE: The long-term durability of the endovascular occlusion of cerebral
      aneurysms is one of the major factors limiting the more widespread use of this
      technique. Long-term occlusion of wide-necked aneurysms has improved with new
      assistive devices that seem to improve aneurysm occlusion while protecting the
      parent vessel. We report the use of a new intracranial stent--the Neuroform
      microstent--in the treatment of patients with wide-necked cerebral aneurysms.
      METHODS: Patients identified as harboring wide-necked intracranial aneurysms were
      evaluated for stent-assisted coiling. After appropriate anticoagulation was
      performed, depending on whether the aneurysm was ruptured or unruptured, the
      Neuroform stent was delivered across the neck of the aneurysm and deployed with a
      coil pusher. After stent placement, standard coil occlusion of the aneurysm was
      achieved in the majority of cases. RESULTS: Fifty-six patients were identified as
      having wide-necked intracranial aneurysms suitable for stent-assisted coiling. A
      total of 49 aneurysms in 48 patients were treated with this procedure. In eight
      cases, stent deployment failed. Forty-one of the aneurysms were initially
      stented, followed by coil placement. Six aneurysms were stented only, and one
      aneurysm was initially coiled, followed by stent placement. There were five
      deaths (8.9%), one of which occurred secondary to a stroke after the procedure
      (1.8%). Four patients (7%) experienced thromboembolic events, three of which were
      considered to have been secondary to the procedure (5.3%). In addition, there
      were two femoral pseudoaneurysms. The overall complication rate was 10.7%. Five
      patients were available for follow-up angiographic evaluation, and their cases
      are discussed. CONCLUSION: Intracranial stenting may overcome important technical
      limitations in current endovascular therapy by improving the occlusion of wide
      necked aneurysms while protecting the parent vessel.

PMID- 15157293
TI  - Correlation of serum brain natriuretic peptide with hyponatremia and delayed
      ischemic neurological deficits after subarachnoid hemorrhage.
AB  - OBJECTIVE: Serum brain natriuretic peptide (BNP) is elevated after subarachnoid
      hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and
      may exacerbate delayed ischemic neurological deficits. We examined the temporal
      relationship between serum BNP elevation, hyponatremia, and the onset of delayed
      ischemic neurological deficits and determined whether serum BNP levels correlated
      with the 2-week outcome after SAH. METHODS: Serum BNP and sodium were measured
      prospectively every 12 hours for 14 days in 40 consecutive patients admitted with
      SAH. All patients remained euvolemic, underwent transcranial Doppler assessment
      every 48 hours, and underwent angiography at the onset of delayed neurological
      deficits. New-onset neurological deficits were attributed to vasospasm only in
      the absence of other causes and when supported by transcranial Doppler or
      cerebral angiography. RESULTS: Sixteen patients (40%) experienced symptomatic
      cerebral vasospasm after SAH. A more than threefold increase in admission serum
      BNP was associated with the onset of hyponatremia (P < 0.05). Mean BNP levels
      were similar between vasospasm and nonvasospasm patients fewer than 3 days after
      SAH (126 +/- 39 pg/ml versus 154 +/- 40 pg/ml; P = 0.61) but were elevated in the
      vasospasm cohort 4 to 6 days after SAH (285 +/- 67 pg/ml versus 116 +/- 30 pg/ml;
      P < 0.01), 7 to 9 days after SAH (278 +/- 72 pg/ml versus 166 +/- 45 pg/ml; P <
      0.01), and 9 to 12 days after SAH (297 +/- 83 pg/ml versus 106 +/- 30 pg/ml; P <
      0.01). BNP level remained independently associated with vasospasm adjusting for
      Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval,
      1.1-1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4
      fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after
      vasospasm onset. Patients with increasing BNP levels from admission demonstrated
      no change (0 +/- 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 +/
      2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without
      increasing serum BNP levels. CONCLUSION: Increasing serum BNP levels
      independently were associated with hyponatremia, significantly increased the
      first 24 hours after onset of delayed ischemic neurological deficits, and
      predicted the 2-week Glasgow Coma Scale score.

PMID- 15157294
TI  - Large sphenoid wing meningiomas involving the cavernous sinus: conservative
      surgical strategies for better functional outcomes.
AB  - OBJECTIVE: The ability to resect meningiomas that involve the medial and anterior
      compartments of the cavernous sinus has been refuted. In this retrospective
      study, we determined the efficacy of total resection of meningiomas that invade
      the cavernous sinus but are restricted to the lateral compartment. METHODS: We
      reviewed the charts of 38 consecutive patients with sphenocavernous,
      clinoidocavernous, and sphenoclinoidocavernous meningiomas who underwent surgical
      treatment. We assessed early and late cranial nerve morbidity, extent of
      resection, and long-term outcome (mean, 96 mo). RESULTS: In all patients, tumors
      exceeded 3 cm diameter. In 22 of 24 patients, total microscopic excision was
      achieved in tumors that involved only the lateral compartment of the cavernous
      sinus and touched or partially encased the cavernous internal carotid artery
      (i.e., modified Hirsch Grades 0 and 1, respectively). In 2 of 24 patients,
      remaining tumor infiltrated the superior orbital fissure. All 14 patients who had
      tumors that encased (with or without narrowing) the cavernous segment of the
      internal carotid artery (Hirsch Grades 2-4) underwent incomplete resection. Among
      38 patients, mortality was 0%, late cranial nerve deficits remained in 6 (16%),
      and late Karnofsky Performance Scale scores exceeded 90 in 34 patients (90%).
      Four patients (10.5%) developed a recurrence or regrowth. Of 20 patients who were
      treated with either linear accelerator-based stereotactic radiosurgery or
      fractionated conformal radiotherapy, 11 had residual tumor and a moderate to high
      proliferative index, 4 had atypical tumors and 1 had angioblastic meningioma
      after total excision, 2 had regrowth, and 2 had recurrent tumors. In 18 (90%) of
      the 20 patients who underwent radiation, tumor size was reduced or controlled.
      CONCLUSION: On the basis of this study and a review of the literature, we
      demonstrate that sphenocavernous, clinoidocavernous, and sphenoclinoidocavernous
      meningiomas of Hirsch Grades 0 and 1 can be excised from the lateral compartment
      of the cavernous sinus without postoperative mortality and with acceptable rates
      of morbidity. Residual tumor in the medial compartment (Hirsch Grades 2-4) may be
      treated with some form of radiation therapy or observation.

PMID- 15157295
TI  - Gamma knife radiosurgery for benign cavernous sinus tumors: quantitative analysis
      of treatment outcomes.
AB  - OBJECTIVE: We review our 8-year experience with gamma knife radiosurgery (GKRS)
      for the treatment of patients with benign cavernous sinus tumors and present a
      quantitative analysis of factors relevant to treatment outcomes. METHODS: From
      1994 to 2002, a total of 139 patients with benign cavernous sinus tumors were
      treated in 145 sessions. Their median age was 53 years, and the median follow-up
      was 3.5 years. The tumors included 57 meningiomas, 76 pituitary tumors (49
      nonfunctional adenomas, 15 prolactinomas, 5 adrenocorticotropic hormone-secreting
      tumors, 6 growth hormone-secreting tumors, and 1 plurihormone-secreting tumor), 4
      schwannomas, 1 hemangioma, and 1 paraganglioma. Sekhar tumor grades were as
      follows: I, n = 28 (20%); II, n = 42 (30%); III, n = 42 (30%); IV, n = 19 (14%);
      and V, n = 8 (6%). The median tumor volume was 3.4 cm(3), and the median
      prescribed dose was 15 Gy defined to the 50% isodose line. RESULTS: A total of
      136 treated tumors (97.8%) were well controlled by GKRS, with low morbidity. For
      meningiomas, 29 tumors (51%) were unchanged and 26 (46%) were smaller at a median
      of 15.2 months. For pituitary tumors, 50 (66%) were unchanged and 25 (33%) were
      smaller at a median of 20.6 months. Improvement in cranial nerve (CN) function
      was seen in 19 (36.5%) of 52 patients with pre-GKRS deficits, and 3 patients
      (2.2%) developed new stable CN deficits after GKRS: 1 patient developed IVth CN
      palsy at 9 months, and 2 developed persistent VIth CN palsies at 43 and 45
      months, respectively, that required surgical correction. Two patients developed
      transient VIth CN palsies at 48 months that self-resolved after another year.
      Endocrine function normalized for all 6 treated patients with a growth hormone
      secreting tumor at a median of 18 months. One of the 5 adrenocorticotropic
      hormone-secreting tumors required retreatment after 17 months because of
      continued cortisol elevation. Thirteen (87%) of 15 prolactinoma patients had
      normalized prolactin levels within 2 years of the procedure; 2 patients relapsed
      by endocrine criteria at 18 and 22 months after GKRS. Two patients with
      normalized prolactin levels completed three normal pregnancies within 3 years of
      treatment. Six patients (4.3%) with a median tumor volume of 8 cm(3) developed
      radiation-induced injury at a median of 36 months after GKRS. Five of these
      patients also underwent external beam radiotherapy and received a median dose of
      52.2 Gy in 30 fractions. Quantitative analysis revealed that the radiation dose
      to critical structures (optic apparatus and pons) is correlated with their
      distance from tumor margins. Underdosed tumor volume, tumor volume, and total
      treated volume are correlated with treatment outcomes. CONCLUSION: GKRS is a safe
      and effective treatment for selected patients with benign cavernous sinus tumors
      and is an important adjunct for treating postoperative tumor residual and/or
      recurrent tumor. Continued analysis of treated patients over an extended time is
      needed to evaluate long-term disease control and potential late GKRS
      complications.

PMID- 15157296
TI  - Failure of gamma knife radiosurgery for mesial temporal lobe epilepsy: report of
      five cases.
AB  - OBJECTIVE: We sought to determine the efficacy of gamma knife radiosurgery (GKRS)
      in controlling mesial temporal lobe epilepsy. METHODS: From August 1999 to
      January 2001, five patients with drug-resistant mesial temporal lobe epilepsy due
      to hippocampal sclerosis underwent GKRS amygdalohippocampectomy. All of the
      patients underwent standard epilepsy preoperative evaluation at the comprehensive
      epilepsy center of the Cleveland Clinic Foundation. A marginal dose of 20 Gy to
      the 50% isodose line was delivered to the mesial temporal structures in all
      patients. Postoperative follow-up included serial neurological examinations,
      neuroimaging studies, and neuropsychological evaluations. RESULTS: None of the
      patients were seizure-free after GKRS. Two patients died, 1 month and 1 year
      after the procedure, as a result of complications related to recurrent seizures.
      At 1 year, T2-weighted magnetic resonance imaging changes were noted in all three
      patients, which suggested radiational changes. None of the three surviving
      patients had any seizure reduction, so 18, 20, and 22 months after GKRS, they
      underwent temporal lobectomy, which resulted in complete seizure control in all
      patients. CONCLUSION: GKRS at the 20-Gy dose level did not lead to seizure
      control in patients with mesial temporal lobe epilepsy due to hippocampal
      sclerosis.

PMID- 15157297
TI  - Anterior cervical fusion using dense cancellous allografts and dynamic plating.
AB  - OBJECTIVE: Dense cancellous grafts provide an open matrix for vascular and
      cellular penetration for early osseous integration. Thus, they provide a better
      biological fusion substrate than cortical or corticocancellous grafts. The aim of
      this study is to evaluate the efficacy of the dense cancellous allografts as a
      substrate for anterior cervical fusion along with instrumentation. METHODS: This
      is a retrospective study of 98 patients who underwent anterior cervical
      discectomy, fusion with dense cancellous allograft bone, and instrumentation
      using dynamic plating between January 2001 and March 2002. Of these procedures,
      60 involved single-level and 38 involved two-level fusions. Subsidence was
      assessed by plain x-rays at 1, 3, 6, and 12 months and fusion at 3, 6, and 12
      months after surgery. Fusion was defined as the appearance of bridging trabecular
      bone and absence of motion in flexion-extension films. RESULTS: The mean follow
      up period was 15 months (range, 12-25 mo). Successful fusion was observed in 70,
      84, and 96% of the patients at 3, 6, and 12 months, respectively. The average
      subsidences for single-level and two-level fusions were 2.0 and 3.2 mm,
      respectively. No allograft- or hardware-related complications were encountered in
      our series. CONCLUSION: Dense cancellous allografts are very effective as bone
      graft substitutes for achieving anterior cervical fusion along with
      instrumentation. Successful fusion was observed in 70% of our patients at 3
      months, with a fusion rate of 96% at 1 year. These allografts provide an
      effective replacement for autologous grafts in cervical interbody fusion.

PMID- 15157298
TI  - Back pain and disability after lumbar laminectomy: is there a relationship to
      muscle retraction?
AB  - OBJECTIVE: Preliminary studies have suggested that prolonged retraction of the
      paraspinal muscle during spinal surgery may produce ischemic damage. We report
      the continuous measurement of intramuscular pressure (IMP) during decompressive
      lumbar laminectomy and its relationship to subsequent back pain and disability.
      METHODS: Twenty patients undergoing two-level decompressive lumbar laminectomy
      for lumbar canal stenosis were recruited. Back pain and disability were assessed
      by use of the Visual Analog Score (VAS), Oswestry Disability Index (ODI), and
      Short-Form 36 (SF-36) Health Survey. During surgery, IMP was recorded
      continuously from the multifidus muscle by use of a pressure transducer. The
      intramuscular perfusion pressure (IPP) was estimated as the difference between
      the patient's mean arterial pressure and IMP. RESULTS: Two muscle retractors were
      used: the Norfolk and Norwich (n = 10) and the McCulloch (n = 10). The mean
      duration of deep muscle retraction was 62.7 +/- 8 minutes (range, 19-133 min). On
      application of deep muscle retraction, there was a rapid and sustained increase
      in IMP (P < 0.001), and overall, the calculated mean IPP approached 0 mm Hg or
      less during this period (P < 0.001). On release of deep muscle retraction, there
      was a rapid decrease in IMP to preoperative levels. The IPP was greater with the
      Norfolk and Norwich than the McCulloch retractor (P < 0.001). Compared with
      preoperative values, there was a decrease in ODI (P < 0.001) and VAS for back
      pain (P < 0.001) at discharge and 4 to 6 weeks and 6 months after surgery. In
      addition, there was a decrease in SF-36 scores at 6 months compared with
      preoperative values (P < 0.001). Total duration of muscle retraction greater than
      60 minutes was associated with worse VAS scores for back pain and ODI and SF-36
      scores for disability at 6 months after surgery (P < 0.05). There was no
      relationship between the VAS, ODI, and SF-36 scores and other parameters
      measured, including the mean IPP, retractor type, operating surgeon, and wound
      length. CONCLUSION: The McCulloch retractor generates a higher IMP than the
      Norfolk and Norwich retractor. However, postoperative improvement in VAS, ODI,
      and SF-36 scores in these patients was associated with a shorter duration of
      muscle retraction and not the degree of IMP or IPP generated. In this respect,
      periodic relaxation of the paraspinal muscle retractors during surgery to allow
      muscle perfusion may help to reduce postoperative back pain and disability.

PMID- 15157299
TI  - Management and outcomes in 318 operative common peroneal nerve lesions at the
      Louisiana State University Health Sciences Center.
AB  - OBJECTIVE: This study analyzes 318 operative knee-level common peroneal nerve
      lesions managed at the Louisiana State University Health Sciences Center between
      1967 and 1999. METHODS: Each patient was retrospectively evaluated for injury
      mechanism, preoperative neurological status, electrophysiological studies, lesion
      type, and operative technique, i.e., neurolysis, suture, or graft repair. All
      lesions in continuity had intraoperative nerve action potential recordings.
      RESULTS: There were 141 stretch/contusions without fracture/dislocations (44%),
      39 lacerations (12%), 40 tumors (13%), 30 entrapments (9%), 22 stretch/contusions
      with fracture/dislocations (7%), 21 compressions (7%), 13 iatrogenic injuries
      (4%), and 12 gunshot wounds (4%). After neurolysis, 107 (88%) of 121 knee-level
      common peroneal nerve lesions with recordable intraoperative nerve action
      potentials recovered useful function. Nineteen patients underwent end-to-end
      suture repair, and 16 (84%) of these achieved good recovery by 24 months. Graft
      repair was performed in 138 peroneal injuries. Thirty-six patients (26%) had
      grafts less than 6 cm long, of which 27 (75%) achieved Grade 3 or greater
      peroneal function. Twenty-four (38%) of 64 patients with 6- to 12-cm grafts, and
      only 6 (16%) of 38 patients with 13- to 24-cm grafts, attained good peroneal
      function. Longer grafts correlated with more severe injuries and thus poorer
      outcomes. Thirty-two (80%) of 40 tumors were resected with preservation of
      preoperative clinical function. CONCLUSION: Surgical exploration and repair of
      peroneal nerve lesions achieved good results with timely operations and thorough
      intraoperative evaluations. Useful function was achieved in 27 (75%) of 36
      patients with grafts less than 6 cm in length and in only 88 (44%) of 202
      patients with grafts greater than 6 cm in length.

PMID- 15157300
TI  - Chiari I malformation associated with ventral compression and instability: one
      stage posterior decompression and fusion with a new instrumentation technique.
AB  - OBJECTIVE AND IMPORTANCE: We describe an alternative surgical technique for
      treatment of Chiari I malformation associated with ventral compression and
      instability of the region. An expansive suboccipital cranioplasty and a rigid
      occipitocervical fixation are performed in one stage. METHODS: The
      occipitocervical fixation is performed by use of metal rods fixed on the cranial
      side by screws inserted into the diploic layer of occipital bone and on the
      caudal side by screws inserted into the pedicle of the axis or in a
      transarticular fashion into the lateral masses of axis and atlas vertebra. A
      large piece of autologous bone is placed in the region between the rostral edge
      of cranial decompression and the axis, with the aim of achieving both expansive
      suboccipital cranioplasty and occipitocervical fusion. RESULTS: We performed this
      procedure in two patients with Chiari I malformation associated with basilar
      invagination and occipitalization of the atlas. Postoperatively, decompression of
      the brainstem and restoration of normal cerebrospinal fluid flow at the
      craniovertebral junction were confirmed radiologically, and the patients were
      relieved of their symptoms. At 1 and 3 years of follow-up, respectively, solid
      bone fusion was observed between the occipital bone and axis in both patients.
      CONCLUSION: Simultaneous posterior decompression and occipitocervical fixation
      with an alternative instrumentation technique is discussed. The procedure can be
      performed regardless of the size of suboccipital craniectomy. Screw insertion
      into the diploic layer of the occipital bone has not been described previously.

PMID- 15157301
TI  - Cadaveric morphometric analysis for atlantal lateral mass screw placement.
AB  - OBJECTIVE: Atlantal lateral mass screws provide an alternative to C1/C2
      transarticular screws and, in some cases, can obviate the need for extending a
      fusion to the occiput. For these reasons, C1 lateral mass screws are becoming
      increasingly popular. However, the critical local anatomy and unfamiliarity with
      this new technique can make C1 screw placement more challenging. METHODS:
      Morphometric analysis was performed on 74 cadaveric spines obtained from the
      Department of Anatomy at the Keck School of Medicine, University of Southern
      California. Critical measurements were determined for screw entry points,
      trajectories, and lengths for application of the technique described by Harms and
      Melcher. RESULTS: The mean height and width for screw entry on the posterior
      surface of the lateral mass were 3.9 and 7.3 mm, respectively. The maximum
      medialized screw trajectory ranged from 25 to 45 degrees (mean, 33 degrees). The
      mean maximal screw length to obtain bicortical purchase was 22.5 mm, and the mean
      minimum screw depth was 14.4 mm. Screw depths varied on the basis of the entry
      point, trajectory, and vertebral morphology. The overhang of the posterior arch
      averaged 11.4 mm (range, 6.9-17 mm). All specimens could accommodate 3.5-mm
      lateral mass screws bilaterally with proper preparation of the entry site.
      CONCLUSION: Significant variations in the morphology of C1 exist. However, the
      large size of the atlantal lateral mass makes screw placement forgiving.
      Preoperative computed tomographic scans and intraoperative fluoroscopy are useful
      in guiding proper screw placement. Close attention should be paid to preparation
      of the screw entry site.

PMID- 15157302
TI  - Superficial temporal artery to middle cerebral artery bypass.
AB  - The superficial temporal artery to middle cerebral artery bypass is an elegant
      procedure that was developed and first performed by M. Gazi Yasargil. It has been
      used by neurosurgeons for more than 30 years in the management of neurovascular
      disorders such as cerebrovascular ischemic disease, moyamoya disease, and complex
      intracranial aneurysms. Mastering the technique requires not only precise and
      fine skills but also devoted training in the microsurgery laboratory. The
      technique presented in this article evolved from the long and vast experience of
      the senior author (DWN) in performing superficial temporal artery to middle
      cerebral artery bypasses for a variety of cerebrovascular conditions.

PMID- 15157303
TI  - Altered arterial homeostasis and cerebral aneurysms: a molecular epidemiology
      study.
AB  - OBJECTIVE: We hypothesized that patients with intracranial cerebral aneurysms
      (IAs) harbor a molecular defect in the process responsible for maintaining
      arterial integrity (arterial homeostasis). In this study, we undertook a
      preliminary assessment of differential expression of key molecules involved with
      each phase of homeostasis: arterial flow modulation, arterial tear and repair,
      and the ensuing extracellular matrix. METHODS: Key molecules from each phase of
      the arterial homeostatic process were selected: prostacyclin-stimulating factor,
      implicated with arterial flow modulation; PNUT and RAI, involved with tissue
      repair and arterial remodeling; and Type III collagen and fibronectin, which are
      key constituents of the extracellular matrix. A small sample of the IA dome was
      harvested at the time of surgical repair from both ruptured and unruptured domes.
      Pericranial vascular tissue was harvested from a sample of the superficial
      temporal artery (STA) or occipital artery from aneurysmal and nonaneurysmal
      patients undergoing craniotomy for unrelated conditions. Statistical analysis
      examining expression of each marker was performed initially using dichotomous
      analysis (presence or absence of expression), followed by an assessment of
      quantitative differences in expression. Initial analysis was restricted to the
      pair consisting of dome and STA harvested from each individual patient. This was
      followed by a pooled analysis in which all domes and STAs were respectively
      pooled. RESULTS: A total of 86 tissue samples were studied, including 24 IA
      domes, STA samples from 43 aneurysmal patients, and STA samples from 19
      nonaneurysmal patients. We found that the degree of prostacyclin-stimulating
      factor and RAI expression was reduced in ruptured aneurysm domes when compared
      with STAs from IA patients (odds ratio, 0.26; 95% confidence interval [CI], 0.08
      0.89; and odds ratio, 0.18; 95% CI, 0.03-0.94, respectively). Type III collagen
      expression also was reduced among ruptured domes when compared with STA (P =
      0.042). These differences were found to be independent of the effects of smoking
      with adjusted odds ratios of 0.25 (95% CI, 0.08-0.77) and 0.18 (95% CI, 0.04
      0.79), respectively, for prostacyclin-stimulating factor and RAI. No
      statistically significant differences were noted among the unruptured domes.
      CONCLUSION: These preliminary data suggest an impaired ability to express
      proteins responsible for flow modulation and arterial repair within the ruptured
      domes when compared with control pericranial tissue. The study generates a
      hypothesis of impaired arterial homeostasis with a reduced ability to modulate
      hemodynamic flow with perhaps increased microinjury. This is exacerbated further
      by an impaired molecular ability to repair the vessel wall, culminating in
      aneurysm rupture. The study has limitations based on the use of pericranial
      tissue as the control and the relatively small sample size. Nevertheless, this
      study suggests that altered arterial homeostasis warrants further investigation
      in hopes of better understanding IA pathogenesis.

PMID- 15157304
TI  - The transgenic arteriovenous fistula in the rat: an experimental model of gene
      therapy for brain arteriovenous malformations.
AB  - OBJECTIVE: To introduce the transgenic arteriovenous fistula model in the rat,
      constructed by interposing mouse aorta in a fistula between the common carotid
      artery and external jugular vein in a nude rat, and to describe the model's
      technical feasibility, long-term patency, and expression of reporter genes.
      METHODS: Carotid-jugular fistulae were surgically created in 112 rats. In 25
      immunodeficient nude rats, wild-type mouse thoracic aorta (TAo) was interposed in
      the fistula; in 10 immunocompetent rats, TAo was interposed; in 19 nude rats,
      transgenic TAo with reporter genes for beta-galactosidase or green fluorescent
      protein was interposed; in 18 nude rats, wild-type mouse ascending aorta was
      interposed; and in 40 rats, a simple fistula was constructed without an
      interpositional graft. Host tolerance and graft viability were analyzed by
      histopathology and immunohistochemistry for CD31 (mouse endothelial cell marker),
      endothelial nitric oxide synthase, smooth muscle actin, fibronectin, beta
      galactosidase, and green fluorescent protein. RESULTS: The transgenic
      arteriovenous fistula was technically feasible and immunologically tolerated in
      nude rats but not in immunocompetent rats. The overall angiographic patency rate
      was 41% with TAo grafts and 56% with ascending aorta grafts, both lower than the
      98% patency rate in fistulae with a single anastomosis and no interpositional
      graft. Mouse endothelium survived on the graft for 3 months according to CD31
      staining, but longer survival by transgenic smooth muscle cells resulted in
      continued expression of beta-galactosidase for 6 months and green fluorescent
      protein for 4 months. Endothelium and smooth muscle in the fistula were
      functional, with normal expression of endothelial nitric oxide synthase as well
      as smooth muscle actin and fibronectin, respectively. CONCLUSION: The transgenic
      arteriovenous fistula model enhances other carotid-jugular fistula models by
      integrating transgenic tissue, thereby creating an experimental system for
      investigating the molecular biology of and gene therapies for arteriovenous
      malformations.

PMID- 15157305
TI  - Chemokine expression in nerve allografts.
AB  - OBJECTIVE: Chemokines (chemoattractant cytokines) play a major role in
      trafficking of cells to areas of inflammation. Infiltration of allograft tissues
      by immunocompetent cells is critical for rejection of donor tissues. The role of
      chemokines in nerve allograft rejection is not clear. We hypothesized that
      chemokines are responsible for attracting macrophages and T lymphocytes into
      nerve allograft tissue, initiating the graft rejection process. METHODS: Lewis
      rats received 4-cm-long peroneal nerve allografts and isografts from ACI and
      Lewis rats, respectively. Twelve hours to 10 days after transplantation, grafts
      were removed and total cellular ribonucleic acid was extracted. Intragraft gene
      expression of several chemokines (cytokine-induced neutrophil chemoattractant,
      macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1, MIP
      1 alpha, and regulated upon activation normal T-cell expressed and secreted
      [RANTES]) were analyzed by reverse transcription-polymerase chain reaction.
      RESULTS: The cytokine-induced neutrophil chemoattractant was expressed in
      allografts and isografts at early time points (12 h to 6 d). Monocyte
      chemoattractant protein-1 messenger ribonucleic acid expression was similarly
      high in both isografts and allografts from 12 hours until 8 days after
      transplantation. MIP-1 alpha, MIP-2, and RANTES were expressed only in
      allografts. Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1 alpha)
      chemokines revealed an early onset (12-24 h), a plateau from 1 to 4 days, and
      expression abruptly declining by Day 6. The lymphocyte chemoattractant RANTES had
      delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline.
      CONCLUSION: Induction of specific chemokine genes precedes nerve allograft
      infiltration by immunocompetent cells. MIP-1 alpha, MIP-2, and RANTES may be
      responsible for recruiting macrophages, granulocytes, and lymphocytes,
      respectively, to the rejecting allograft. In future studies, blockade of these
      specific chemokines or their receptors may prove to delay or prevent nerve
      allograft rejection.

PMID- 15157306
TI  - Epidermal growth factor receptor antagonists: novel therapy for the treatment of
      high-grade gliomas.
AB  - Overactivation of epidermal growth factor receptor (EGFR) signaling has been
      recognized as an important step in the pathogenesis and progression of multiple
      forms of cancer of epithelial origin. This knowledge has led to a surge of
      interest in novel anticancer therapies targeting key constituents of the EGFR
      signal transduction pathway. Several molecular strategies have been developed
      recently to modulate either EGFR or the downstream signal beyond the cell surface
      receptor. The important role of aberrant EGFR signaling in the progression of
      malignant gliomas makes EGFR-targeted therapies of particular interest in this
      form of cancer. The use of anti-EGFR therapies against malignant brain tumors,
      although in its infancy, promises to yield exciting results as these new drugs
      probably will enhance the usefulness of existing therapies.

PMID- 15157309
TI  - Historical background of stereotactic surgery: Reflections on stereotactic
      surgery and the introduction of microelectrode recording in montreal.

PMID- 15157307
TI  - The spinal cord and its roots according to Galen.
AB  - Galen's methodological approach to medicine anticipated modern rules. His
      experiments on the spinal cord contributed greatly to our knowledge of this
      structure by reporting the variegated pattern of neurological impairment after
      sectioning at different levels. His approach to injuries of the spinal roots and
      peripheral nerves documents both diagnostic skill and intellectual honesty.

PMID- 15157308
TI  - Preclinical evaluation of a novel intracerebral microinjection instrument
      permitting electrophysiologically guided delivery of therapeutics.
AB  - OBJECTIVE: This series of studies was designed to evaluate the function of a new
      neurosurgical instrument for precision injection of therapeutics within the
      central nervous system. METHODS: An intracerebral microinjection instrument was
      designed to 1) allow multiple injections to be placed in three-dimensional space
      within a target structure from a single proximal brain penetration, 2) incur
      minimal injury at the site of injection, 3) enable accurate microvolume
      injections, and 4) permit electrophysiological recording during the injection
      procedure. Rats received injections of fluorescent microspheres or suspensions of
      labeled cells to test instrument function and level of induced trauma. A rodent
      model of stroke was used to test the instrument's ability to record
      electrocorticograms or somatosensory evoked potentials from normal and damaged
      tissue. RESULTS: Microliter volumes of fluorescent microspheres were accurately
      placed at predetermined sites within the rat striatum. Reactive gliosis was
      markedly reduced using the intracerebral microinjection instrument when compared
      with standard cannulas. In a stroke model, electrophysiological recording with
      the instrument allowed discrimination between viable and nonviable ischemic
      tissue, and function of pathways or circuits was assessed using evoked
      potentials. Embryonic stem cells grafted immediately after electrophysiological
      recordings demonstrated robust long-term survival. CONCLUSION: The intracerebral
      microinjection instrument enables electrophysiologically guided microinjection of
      therapeutics to target areas with exquisite accuracy while incurring minimal
      local trauma and reactive gliosis at the injection site. The instrument also
      permits minimally invasive, multiple injections to be disseminated in three
      dimensional space within the target region from a single proximal penetration of
      the brain.

PMID- 15157310
TI  - Extensive spinal cord infarction after posterior fossa surgery in the sitting
      position: case report.
AB  - OBJECTIVE AND IMPORTANCE: Spinal cord injury is a rare complication of
      neurosurgery performed with the patient in the sitting position. Previous reports
      showed that the level of injury is usually located at or near the C5 segmental
      spinal level, and the term midcervical quadriplegia has been proposed. Extensive
      spinal cord and lower brainstem infarction also can occur after posterior fossa
      surgery performed with the patient in the sitting position. CLINICAL
      PRESENTATION: We describe a 45-year-old woman who was operated on in the sitting
      position because of a fourth ventricular pilocytic astrocytoma. After surgery,
      the patient experienced quadriplegia. INTERVENTION: T2-weighted magnetic
      resonance imaging scans revealed a long, hyperintense area within the
      cervicothoracic spinal cord that was extended to the lower pons and was
      consistent with infarction. There was no evidence of previous spine disease. The
      patient died 6 weeks later of respiratory failure. CONCLUSION: We speculate that
      alteration of spinal cord blood flow by stretching of the cervical spinal cord
      and spinal epidural venous engorgement might have caused this devastating
      complication.

PMID- 15157311
TI  - Extracranial vertebral artery aneurysm ruptured into the thoracic cavity with
      neurofibromatosis type 1: case report.
AB  - OBJECTIVE AND IMPORTANCE: We are sometimes involved in the care of patients with
      neurofibromatosis Type 1 because of the associated disorders of cervicocerebral
      vessels. However, extracranial vertebral artery aneurysm in neurofibromatosis
      Type 1 is very rare. We present the first reported case of a rupture of an
      extracranial vertebral artery aneurysm into the thoracic cavity in a patient with
      neurofibromatosis Type 1. CLINICAL PRESENTATION: A 52-year-old woman who
      presented with a decrease in left-sided grip and numbness of the left upper limb
      was admitted. During history taking, she developed shock. Radiological
      examination revealed that a left extracranial vertebral artery aneurysm had
      ruptured into the thoracic cavity. With consciousness decreasing gradually
      because of hemorrhagic shock, the patient became comatose. INTERVENTION: Balloon
      occlusion of the vertebral artery proximal to the aneurysm was performed and
      surgical ligation was attempted, but cardiac arrest occurred immediately after
      the beginning of surgery, and the patient died. The vertebral artery proximal to
      the aneurysm was removed for pathological examination. CONCLUSION: In this case,
      the changes noted were interpreted as changes showing fragility of the vascular
      wall secondary to neurofibromatosis Type 1. Patients with neurofibromatosis Type
      1 exhibit disorders of cervicocerebral vessels, and in some cases progression may
      follow a violent course. Periodic follow-up of such patients and early diagnosis
      are important.

PMID- 15157312
TI  - Unanticipated complication of percutaneous radiofrequency trigeminal rhizotomy:
      rhinorrhea: report of three cases and a cadaver study.
AB  - OBJECTIVE AND IMPORTANCE: Several neurosurgical procedures have been developed
      for the treatment of idiopathic trigeminal neuralgia: vascular decompression of
      the trigeminal root in the brainstem, percutaneous trigeminal ganglion
      procedures, and external beam radiosurgery. Percutaneous radiofrequency
      electrodes target the trigeminal fibers in the gasserian ganglion through the
      foramen ovale. Several complications of radiofrequency trigeminal rhizotomy (RF
      TR) have been described, including puncture of the carotid artery, the cavernous
      sinus, and the cranial nerves. This study presents a very rare complication of
      percutaneous RF-TR, rhinorrhea, and attempts to define its mechanism. CLINICAL
      PRESENTATION: Of 2375 patients with idiopathic trigeminal neuralgia who underwent
      2958 percutaneous RF-TR procedures, 3 developed subsequent rhinorrhea, which
      resolved spontaneously in 2 to 3 days. TECHNIQUE: Two formalin-fixed cadavers
      were dissected to demonstrate the relationship between the foramen ovale and the
      tuba auditiva and the mechanism of rhinorrhea. CONCLUSION: This article presents
      a very rare complication of RF-TR. Rhinorrhea and/or cerebrospinal fluid fistulae
      in the nasopharyngeal cavity are benign complications of RF-TR that result from
      puncturing both the membranous portion of the tuba auditiva (eustachian tube) and
      Meckel's cave with the rhizotomy needle.

PMID- 15157313
TI  - Vertebral body granuloma of the cervical region after pencil injury.
AB  - OBJECTIVE AND IMPORTANCE: Granuloma formation has been reported as a rare
      complication of pencil lead injury. Insufficient data exist regarding pencil lead
      injuries of the cervical spine. We present the findings in an 18-year-old male
      patient with secondary granuloma formation after a penetrating transoral pencil
      injury. We suggest that imaging characteristics and a detailed history will
      assist with the diagnosis of such lesions. CLINICAL PRESENTATION AND
      INTERVENTION: The patient was an 18-year-old man who presented with cervical
      pain. His history included falling as a child while having a pencil in his mouth.
      T2-weighted imaging studies documented a 1- x 1-cm enhancing lesion posterior to
      the vertebral body at the C3 level. The patient underwent a C3 vertebrectomy, and
      specimens were notable for infection, pencil lead, and granuloma formation.
      CONCLUSION: In the evaluation of a potential granuloma or mass lesion of the
      cervical spine in a child or adolescent, the differential diagnosis may include a
      neoplasm. Although computed tomography is an ideal tool to detect foreign
      objects, including pencil leads, only awareness of the potential for pencil lead
      injuries and that pencil lead fragments may remain unrecognized on computed
      tomographic scans will assist the physician in diagnosing such injuries.

PMID- 15157314
TI  - Temporal lobotomy in the surgical management of epilepsy: technical report.
AB  - OBJECTIVE: To describe the technique of temporal lobotomy and demonstrate that it
      may produce results equivalent to anterior temporal lobectomy in the control of
      drug-resistant complex partial seizures of anterior temporal lobe origin.
      METHODS: Patient selection and evaluation was similar to that for other patients
      undergoing anterior temporal lobectomy, with the exception that the 10 selected
      patients all demonstrated extensive lobar or hemispheral atrophy on magnetic
      resonance imaging or computed tomographic scans. The lobotomy technique involved
      posterior and superior disconnection, each of which was broken down into lateral
      and mesial components. RESULTS: At last follow-up, seven patients were seizure
      free, one had rare seizures, and two had a less than 90% decrease in seizures.
      These outcomes are similar to those in our overall temporal lobectomy series. One
      patient who underwent left-sided temporal lobotomy had a speech fluency deficit
      postoperatively. CONCLUSION: Temporal lobotomy seems to be an effective
      disconnective procedure in the treatment of drug-resistant temporal lobe
      epilepsy. Larger series will be needed to better define its role in the
      management of this condition.

PMID- 15157316
TI  - [The study on methylation of gene IGSF4 promoter in acute leukemia cells].
AB  - To study whether gene IGSF4 was inactived by methylation in leukocytic cells,
      expression of IGSF4 was examined before and after treatment with demethylating
      agent in U937, Molt4 and HL-60 leukemia cell lines by means of RT-PCR. The
      methylation of promoter in U937, Molt4 and HL-60 cells as well as 21 acute
      leukemia patients was analyzed by MS-PCR. The results showed that methylation of
      IGSF4 promoter was inactived and could be reversed by treatment with a
      demethylating agent in U937, Molt4 and HL-60 cell. IGSF4 promoter methylation was
      detected in 57.1% of acute leukemia patients. There is no difference in incidence
      of IGSF4 promoter methylation between acute myelocytic leukemia and acute
      lymphocytic leukemia. In conclusion, IGSF4 is frequently inactived in acute
      leukemia and is a good candidate for the leukemia suppressor gene. As a normal
      suppressor gene, it may play an important role in inhibiting the development of
      leukemia, and the methylation of gene IGSF4 may be a good index in monitoring
      relapse of leukemia.

PMID- 15157317
TI  - Mutation analysis of hematopoietic cell phosphatase gene in acute leukemia.
AB  - The hematopoietic cell phosphatase (HCP or SHP-1), the SH2 domain contain protein
      tyrosine phosphatase, is a crucial negative regulator in the process of
      hematopoietic cell development, proliferation and receptor-mediated mitogenic
      signaling pathways, and its mutation is responsible for the over-expansion and
      inappropriate activation of myelomonocytic population in motheaten mice. The aim
      of the study was to evaluate the role of the HCP gene in leukemogenesis. Bone
      marrow and/or peripheral blood from 32 acute myeloid leukemia (AML) patients, 9
      acute lymphocytic leukemia (ALL) patients, 8 leukemia cell lines and 50 normal
      controls were analyzed by reverse transcription-polymerase chain reaction (RT
      PCR) based on single strand conformation polymorphism (SSCP) and sequencing. RT
      PCR showed that all samples expressed HCP gene, only one missense mutation at
      codon 225 (AAC to AGC, Asn to Ser) within N-terminal SH2 domain was found in an
      ALL patient. In addition, four polymorphic base substitutions were detected in
      codon 69, 85, 86 and 266, respectively. In conclusion, mutation of HCP gene is an
      infrequent genetic aberration which may only play a role in pathogenesis of a
      small part of leukemia, however, its significance needs to be further clarified.

PMID- 15157318
TI  - [Ex vivo expansion of megakaryocyte progenitor cells from human cord blood in
      serum-free culture].
AB  - Prolonged thrombocytopenia is a puzzling problem following umbilical cord blood
      (CB) transplantation. It might be the result of inadequate megakaryocyte
      progenitors and the arrest in the megakaryocyte maturation. It is an important
      method to solve the problem by transfusing ex-vivo expanded CB megakaryocyte
      progenitor cells into the patients to shorten the duration of platelet recovery.
      However, the most optimal condition of expansion has not been established so far.
      In the study, cord blood mononuclear cells (MNC) were cultured in serum-free
      medium with TPO, IL-3, SCF and IL-6. The numbers of MNC, CFU-MK and CD41(+) cells
      were measured at 0, 6, 10 and 14 days, in order to find the best cytokine
      combination and optimal harvest time point for clinical use. The results showed
      that the megakaryocyte progenitors most efficiently expanded with the cytokine
      combination including TPO, IL-3, SCF and IL-6. The time point of maximal CFU-MK
      growth is day 10. At 10 days, the numbers of CFU-MK and CD41(+) cells expanded by
      6.8- and 8.8-fold respectively. In conclusion, in vitro, the cytokine cocktail
      including TPO, IL-3, SCF and IL-6 was the most optimal cytokine combination which
      stimulates the ex vivo expansion of megakaryocyte progenitors in CB MNC and serum
      free medium. The maximal CFU-MK colonies were harvested at 10 days, that may be
      an optimal harvest time for clinical transfusion.

PMID- 15157319
TI  - The effects of interferon-gamma on the expression of the cyclin D isoforms in
      cord blood hematopoietic stem/progenitor cells.
AB  - To explore the hematopoiesis inhibition mechanisms of interferon-gamma (IFN
      gamma), the effects of IFN-gamma on the expression of the cyclin D in the
      umbilical cord blood hematopoietic stem/progenitor cells were observed. In the
      experiments the CD34(+) cells were isolated from the cord blood with MIDI-MACS
      system; semi-solid methylcellulose culture technique was used to measure the
      formation of CFU-GM; the expression levels of cyclin D isoforms were assayed by
      semi-quantitative RT-PCR, after the hematopoietic stem/progenitor cells were
      incubated with IFN-gamma. The results indicated that IFN-gamma could inhibit the
      formation of CFU-GM and down-regulate the expression of cyclin D2 and cyclin D3
      at the mRNA level. It is concluded that the IFN-gamma could inhibit the
      proliferation of hematopoietic stem cells and down-regulate the expression of
      cyclin D, that may be one mechanism underlying the hematopoietic inhibition of
      IFN-gamma.

PMID- 15157320
TI  - [The effect of all-trans retinoid acid and sodium selenite (Na2SeO3) on VEGF and
      its receptor expression in HL-60 cells].
AB  - In order to investigate the effect of non-medullar toxicity drug - all trans
      retinoid acid (ATRA) and cancer preventive trace element-selenium compound -
      sodium selenite (Na(2)SeO(3)) on the expression of vascular endothelial growth
      factor (VEGF) and its receptor in HL-60 cells, the expression of VEGF and its
      receptor in HL-60 cells were detected by ELISA technique and flow cytometry
      before and after treatment with two drugs. The results showed that the mean VEGF
      concentrations in the cultural supernatant of 5 and 10 micro mol/L ATRA-treated
      HL-60 cells for 48 and 72 hours were lower than those of the control group
      without adding ATRA. The differences between the ATRA-treated groups and the
      control group were statistically significant (P = 0.001, P = 0.000, P < 0.01,
      respectively). The levels of VEGF-R on the surface of HL-60 cells also decreased
      after treatment with ATRA of 5 and 10 micro mol/L for 72 hours, but at 48 hours
      the expression rates of VEGF-R on HL-60 cells of the two ATRA treated groups were
      not significantly decreased. At 48 and 72 hours, Na(2)SeO(3) of 5 and 10 micro
      mol/L had no obvious effect on HL-60 secreting VEGF, but notablely inhibited the
      expression of VEGF-R. In conclusion, ATRA could inhibit the expression of VEGF
      and its receptor in HL-60 cell. Na(2)SeO(3) could not inhibit the expression of
      VEGF in HL-60 cell, but could decrease the receptor expression of VEGF, which
      mechanism should be further studied. ATRA and Na(2)SeO(3) had not obvious
      medullar-inhibition, but anti-angiogenesis activity. It is suggested that
      combination of two drugs with conventional therapy may enhance the effect of
      radiotherapy and chemotherapy, and reduce the dose and thus toxicity of
      chemotherapeutic agents.

PMID- 15157321
TI  - [Combined analysis on morphology, immunology, cytogenetics and molecular biology
      (MICM) classification of 55 patients with acute promyelocytic leukemia].
AB  - To investigate the value of bone marrow morphology, immunology, cytogenetics and
      molecular biology (MICM) examination in the diagnosis of acute promyelocytic
      leukemia (APL) and their relations of each other, the MICM data of 55 APL
      patients were analyzed retrospectively. The result showed that the accuracy rate
      of morphological diagnosis based on FAB classification could reach 96.4%; CD33
      and CD13 antigen were co-expressed the highest in immunophenotyping
      (CD33(+)CD13(+) occupied 96.4%); cytogenetic abnormality containing t (15;
      17)(q22; 21) accounted for 87.3%, translocation of chromosomes (simple type) of
      100% t (15; 17)(q22; 21) occupied 75%, other involved chromosomes included 1, 8,
      9, 11, 12, 21; the positive rate of PML/RARalpha gene also reached 96.4%; the
      accuracy rate of APL diagnosis by combining MICM measure was 100%. In conclusion,
      the bone marrow morphology still remains to be base for diagnosis of APL, but the
      combined analysis of MICM could obviously enhance the accuracy of diagnosis for
      APL. The MICM examination may provide a new approach to find subtype of APL.

PMID- 15157322
TI  - [Inhibiting effect of vascular endothelial growth factor (VEGF) antisense
      oligodeoxynucleotides on VEGF expression in U937 cell].
AB  - To study the effect of VEGF fully phosporothioated antisense oligodeoxynucleotide
      (VEGF-ASODN) on VEGF expression in acute monocyte leukemic cell line U937 in
      vitro, U937 cells were incubated with VEGF-ASODN at concentrations of 10, 20 and
      30 micro mol/L or scrambled sequence as compared with negative control. The
      expression of VEGF mRNA was measured by semi-quantitative RT-PCR. The expression
      of VEGF protein was measured by Western blot. The result showed that VEGF-ASODN
      had obviously inhibitive effect on expression of VEGF in U937 cell, as compared
      with scrambled sequence and negative control (P < 0.05). Scrambled sequence group
      had no significant difference compared with negative control group (P > 0.05). It
      is concluded that the expressions of VEGF mRNA and protein in leukemic cell line
      U937 are down-regulated by VEGF-ASODN.

PMID- 15157323
TI  - [Inhibiting effects of stroma cell drived factor 1 (SDF-1) on proliferation of
      human acute myelocytic leukemia cell HL-60].
AB  - This study was aimed to investigate the importance of chemokine SDF-1 in
      maintaining proliferation ability of acute myelocytic leukemia cell line HL-60
      when the effects of SDF-1 on HL-60 cell proliferation were inhibited. Marrow
      stromal cells were cultured and co-cultured with HL-60 cells, and SDF-1 activity
      was blocked with anti-CXCR4 McAb. HL-60 cell activity was detected by MTT while
      cell cycle and the expression of CXCR4 on HL-60 cell membrane were observed by
      flow cytometry meanwhile. The internal calcium ionic concentration in HL-60 cell
      was detected as well before and after treated with 12G5. The results showed that
      12G5 down-regulated the expression of CXCR4 on HL-60 cell membrane; HL-60 cells
      at G(0)/G(1) phase increased, but decreased at S phase; survive rate of leukemia
      cells reduced; the intercellular calcium ionic concentration of HL-60 cell
      decreased after treated with 12G5. It was concluded that brockage of the SDF-1
      activity may inhibit proliferation of leukemia cell at certain level.

PMID- 15157324
TI  - [Study on the relationship between [Ca2+]i and the MDR formation in K562/A02
      cells].
AB  - To explore the relationship of multidrug resistance formation in K562/A02 cells
      with the intracellular concentration of [Ca(2+)]i, the cytotoxicities of
      daunorubicin (DNR) were assayed by MTT method, the variations of [Ca(2+)]i of
      K562 cells and K562/A02 cells after treatment of Tet, DRL and DNR alone or in
      combination were detected by using Fura-2/AM. The results showed as follows: (1)
      The cytotoxicities of DNR to cell line K562/A02 were enhanced by 1 micro mol/L
      Tet or 5 micro mol/L DRL. Their IC(50) was (7.28 +/- 2.06) micro g/ml and (7.58
      +/- 3.44) micro g/ml; multiple of their reversal effect was 2.94 and 2.82, but
      IC(50) of combined Tet and DRL was (1.66 +/- 0.41) micro g/ml. Its reverse effect
      distinctly increased by 12.9 times. (2) The [Ca(2+)]i in K562/A02 cells were
      higher than that in K562 cells. (3) One micro mol/L Tet and 5 micro mol/L DRL
      alone increased the [Ca(2+)]i in K562/A02 cells time-dependently and there was
      antagonism when both were used. It is concluded that high [Ca(2+)]i is supposed
      to be a reason of MDR in K562/A02 cells, the action of resistance modifying
      agents (RMA) in MDR reverse course, however, needs further research.

PMID- 15157326
TI  - [Cytogenetic and clinical characteristics in 31 cases of blood diseases with
      aberrations at short arm of chromosome 12].
AB  - To investigate the cytogenetic and clinical characteristics in patients with
      abnormalities at the short arm of chromosome 12, chromosome specimens were
      prepared by 24-hour culture of bone marrow cells and undergone karyotype analysis
      by G-banding technique. The results showed that aberration at the short arm of
      chromosome 12 were detected in 16 cases with 12p balanced translocation, in 10
      cases with 12p deletion, 6 cases with 12p addition, and in 1 case with inversion
      12. By complex karyotype classification, 12p translocation included 6 simple
      aberrations, 6 complex aberrations, and 4 highly complex aberrations; while 12p
      deletion were mainly composed of highly complexity of aberration. Patients
      consisted of acute leukemia, myelodysplastic syndrome, chronic myelogenous
      leukemia and so on. Clinical follow-up data were available in 14 patients, in
      which 8 cases of acute leukemia were treated with conventional chemotherapy only.
      Three of them attained complete remission, and the median survival time in 8
      patients was 5.5 months. In conclusion, the aberrations at short arm of
      chromosome 12 were involved in a broad spectrum of haematological malignancies,
      and the karyotypes showed most complexity of aberration with low remission rate
      and short survival in clinic.

PMID- 15157325
TI  - [Effects of leukemia bone marrow stromal cells on resistance of co-cultured HL-60
      to idarubicin].
AB  - To study the role of hematopoietic microenvironment abnormality in development of
      minimal residual disease and its mechanism, the viability of HL-60 cells was
      investigated by means of bone marrow stromal cell culture system or co-culture
      system of bone marrow stromal cell with HL-60 cells and idarubicin (IDA), flow
      cytometry and ELISA. The results showed that viability of HL-60 cells gradually
      decreased along with the increase of IDA dose and prolongation of culture time.
      Amount of HL-60 cells co-cultured with leukemia bone marrow stramal cells was
      significantly increased as compared with that of the control (P < 0.05). Bone
      marrow stromal cells or stromal cell conditioned medium reduced the effect of IDA
      on HL-60 cells in culture. In conclusion, leukemia bone marrow stromal cells
      contribute to increasing resistance of HL-60 cells to chemotherapeutic agents,
      and play some role in developing minimal residual disease.

PMID- 15157327
TI  - [Hematological abnormality and clinical characteristics in systemic lupus
      erythematosus].
AB  - To investigate the hematological abnormality and clinical characteristics in
      systemic lupus erythematosus (SLE), the hematological data of 58 SLE and the
      curative effects of corticosteroid and immunosuppressive agents on SLE were
      retrospectively analysed by using SPSS/PC software. The results showed that the
      incidence of hematological abnormalities in 58 cases was as follows: 50 cases of
      hemogram abnormality (86.2%), 41 of anemia (70.7%), 34 of thrombocytopenia
      (58.7%), 37 of leukopenia (63.8%). Peripheral cytopenia of every cell lineage was
      common in SLE. The cell abnormalities of two or three lineages were seen in 41
      cases (70.7%). The initial symptoms with hematological abnormality were found in
      12 cases (20.7%), 7 out of 12 cases were erroneously diagnosed as hematology
      diseases (12.1%). In 30 out of 58 patients, the results of bone marrow
      examination showed that 23 had hyperplasia (76.7%) and 7 were hypoplasia. In 25
      out of 38 cases, splenomegaly (65.8%) was found by B ultrasonography. In 25
      patients with SLE receiving Coombs test, 3 were positive (12.0%). PAIg increased
      in 16 out of 22 cases of thrombocytopenia (72.7%). 26 cases of SLE with two or
      three lineage cytopenia in peripheral blood were treated by corticosteroid and
      immunosuppressive agent. The hemogram improved in all patients including 6 cases
      of bone marrow hypoplasia. It is concluded that the hematological abnormalities
      are frequent in SLE patients, which are short of specialty. The cytopenia of two
      or more lineage in peripheral blood is most common when bone marrow shows
      hyperplastic. The therapy with corticosteroid and immunosuppressive agents is
      efficacious.

PMID- 15157328
TI  - [Effect of ligustrazine on the expression of LFA-1 and ICAM-1 in bone marrow
      transplantation recipient mice].
AB  - The objective of study was to investigate the effect of ligustrazine on the
      expression of LFA-1 and ICAM-1 in bone marrow and the mechanism of hematopoietic
      reconstitution after bone marrow transplantation (BMT). The 150 mice were
      randomly divided into 3 groups: normal group, saline group and ligustrazine
      group. The normal group was not treated. The saline group was given normal saline
      (0.2 ml/mouse, twice a day) through gastric tube, while the ligustrazine group
      was given ligustrazine (0.2 ml/mouse, twice a day) through gastric tube. At days
      7, 14, 21 and 28 after BMT, the survival rate, colony forming unit of spleen (CFU
      S), peripheral blood cells, bone marrow mononuclear cells (BMMNC), histologic
      changes of bone marrow, as well as the expression level of LFA-1 and ICAM-1 were
      observed. The results showed that in ligustrazine group CFU-S counts on day 10
      and survival rate, WBC and Plt amount in peripheral blood, BMMNC counts,
      hematopoietic tissue volume as well as the expression level of LFA-1 at 7, 14,
      21, 28 days after BMT were higher than in saline group (P < 0.01 or P < 0.05).
      However, mature RBC volume and expression level of ICAM-1 were lower than in the
      saline group (P < 0.01 or P < 0.05). Furthermore, fat tissue volume was higher at
      7 and 14 days (P < 0.01) and was lower at 21 and 28 days (P < 0.01) after BMT
      than in the saline group. It is concluded that ligustrazine could improve bone
      marrow microenvironment and promote hematopoietic reconstitution.

PMID- 15157329
TI  - [Experimental study on quantitative monitoring engraftment of an adult with mixed
      umbilical cord blood transplantation].
AB  - The purpose of this research was to monitor quantitatively and study the dynamic
      changes and development rules of engraftment, chimera types, as well as relative
      amount of donor cells after allogeneic transplantation of mixed umbilical-cord
      blood from two units. An adult patient with acute myeloid leukemia received two
      units HLA one locus mismatched unrelated umbilical cord blood transplantation
      (2.5 x 10(7)/kg karyocytes in umbilical cord blood unit 1, and 1.53 x 10(7)/kg
      karyocytes in umbilical cord blood unit 2). Nine STR loci of the blood sample
      before and after transplantation were determined by quantitative detecting
      technique with fluorescence labeling polymerase chain reaction, while the
      engraftment and chimera types were qualitatively evaluated by comparing
      differential loci between the recipient and the donors. Then the relative
      proportion of chimera from two units of umbilical-cord blood in the patient after
      transplantation was calculated according to the differential gene peak areas of
      two donors on 377XL DNA sequencer after fluorescence scanning, and the
      engraftment level and the development rules of donor cells were analyzed. In
      addition, the results were also compared with that of HLA loci distinct analysis
      for engraftment. The results showed that two umbilical cord blood units at 15
      days after transplantation were engrafted simultaneously and revealed a complete
      chimerism of the two. The relative amounts of chimera from unit 1 vs that of unit
      2 were 51.3% vs 48.7%; subsequently relative amounts of chimera from unit 1 went
      up to 70.0% at 30 days, and that from unit 2 declined to 30.0%. However, at 52
      days, only the genotype of umbilical cord blood unit 1 was detected, so that the
      engraftment turned to a complete chimerism of a single donor type. The one with
      fewer karyocytes was rejected and the one with more karyocytes finally engrafted
      in long-term. It is concluded that quantitatively detecting STR chimera with
      fluorescence labeling polymerase chain reaction can depict precisely the
      engraftment level and the change course of two umbilical cord blood units. It
      provides an accurate and reliable experimental basis for clinical umbilical cord
      blood application and donor selection, and is proved to be feasible for adult
      transplantation by using dual unit of umbilical-cord blood with HLA one locus
      mismatched at the same time.

PMID- 15157330
TI  - [Pulmonary complications in haploidentical bone marrow transplantation].
AB  - To explore the occurrence patterns of pulmonary complications at different stages
      in haploidentical bone marrow transplantation, a series of clinical data as the
      onset time, etiology, management choices and prognosis in 18 patients with
      pulmonary disorders were summarized. The results showed that in 18 out of 70
      patients after bone marrow transplantation occurred pulmonary complications which
      included pneumonia affected by bacteria (7 cases), fungus (5 cases) and
      cytomegalovirus (CMV, 4 cases), bronchiolitis obliterans organizing pneumonia
      (BOOP, 1 case), and idiopathic pneumonia syndrome (1 case), out of which 8 cases
      died. Fungal and CMV pneumonia occurred predominantly 2 to 3 months after
      transplantation, whereas bacterial pneumonia was observed in the duration of 3 to
      12 months and 4 cases of them suffered from secondary fungal infections during
      treatment. BOOP and idiopathic pneumonia syndrome were diagnosed 12 months and 50
      days after transplantation respectively. IN CONCLUSION: pulmonary complications
      were commonly seen in haploidentcal bone marrow transplantation, and fungal
      pneumonia might be the main cause that needs intensive management.

PMID- 15157331
TI  - [In vivo transfection and expression of human coagulant factor VIII cDNA in
      mice].
AB  - The aim is to observe the expression of human factor VIII gene in mice tranduced
      in vivo and ex vivo. The vector pLNC-FVIII BD was generated by cloning a B-domain
      deleted (760aa-1639aa) FVIII cDNA (FVIIIBD cDNA) into retroviral vector pLNCX. 2
      x 10(6) of mouse bone marrow stroma cells transduced by LNC-FVIII BD were infused
      into 4-week-old BALB/c mice by tail-vein injection. pLNC-FVIII BD was conjugated
      with PAMAM dendrimer to form complex PAMAM-pLNC-FVIII BD, with which C57BL/6J
      were injected by tail vein (200 micro l contained 15 micro g/mouse) and
      sacrificed at days 1, 2, 7, 14, 21 and 28, respectively after injection. Tissue
      such as liver, spleen, lung and kindney were harvested, with which the
      transcription were detected by means of RT-PCR. In addition, blood was collected
      to be measured human FVIII Ag, human FVIIIc and anti-FVIII of human inhibitors.
      The results showed that the highest level of human FVIII in the recipient BALB/c
      mice was 8.6 +/- 1.44 ng/ml detected on the first day post-injection; anti-FVIII
      antibodies were detected from the first week post-injection, and then the level
      of FVIII Ag decreased and cannot be measured on the fourth week. In the C57BL/6J
      mice physiological level of human FVIII was expressed in plasma at 48 hours after
      injection and the average human FVIIIc was 0.62 U/ml and the average human FVIII
      Ag was 115.5 ng/ml, and gradually reduced later. Anti-FVIII of human inhibitors
      was not revealed all the time. Syngene image scanning demonstrated that the
      transcription of the human FVIII BD cDNA occurred mainly in spleen and lung, and
      secondarily in liver and kidney. No side effects of PAMAM-pLNC-FVIII BD were
      observed in mice tissue by pathological examination at 4 weeks. In conclusion,
      retrovirus-transduced bone marrow stroma cells effectively produced human FVIII
      after ex vivo transduction, but the development of anti-FVIII antibodies in
      recipient mice influenced the expression level. The human FVIII gene can
      successfully be transduced in vivo through injecting PAMAM-pLNC-FVIII BD cDNA
      into mice intravenously. There was physiological level expression of human FVIII
      in plasma at 48 hours after injection and the average human FVIIIc is 0.62 U/ml
      and the peak in the six mice was 0.89 U/ml, and gradually reduced later.

PMID- 15157332
TI  - [Purification and characterization of platelet aggregation inhibitor component
      from venom of agkistrodon halys pallas].
AB  - Snake venom proteins,particularly from the viper and elapid families, have been
      known to contain a number of platelet active components including what cause
      platelet aggregation or inhibit platelet aggregation. Some of them have potential
      clinical usefulness for the treatment of human hemorrhagic or thrombotic disease.
      Agkistrodon halys pallas belonging to viper family is only growing in China. The
      aim of this study was to purify a human platelet aggregation inhibitor from venom
      of Agkistrodon halys pallas and determine its biochemical character. Whether a
      component could inhibit human platelet aggregation was act as a method to follow
      the tracks of the protein. Crude venom of Agkistrodon halys pallas was loaded
      onto a DEAE-Sepharose CL-6B chromatography column could gain 6 peaks. A platelet
      inhibitor with molecular mass of 65 kD on SDS-PAGE, was purified from peak 2 by
      Sephadex G-75 gel filtration and SP-Sepharose, Mono Q on FPLC. It could inhibit
      human platelet aggregation induced by ADP, collagen without activities of
      phospholipase A2, esterase, fibrinogenolytic. It is concluded that a platelet
      inhibitor can be isolated and purified from venom of Agkistrodon halys pallas and
      its inhibition of platelet aggregation is does-dependent.

PMID- 15157333
TI  - [Expression of von willebrand factor-A3 domain in E coli and its biological
      function].
AB  - The interaction among collagen, von Willebrand factor (vWF) and glycoprotein Ib
      axis is the first step in hemostasis and thrombosis, especially under high shear
      condition. To develop a new remedy of anti-thrombosis, mRNA from endothelial
      cells was extracted, and reverse transcription PCR was adopted to amplify DNA of
      interest. After sequencing, recombinant expression vector was constructed. The
      amplified DNA fragment of vWF domain A3 was inserted into expression vector with
      6 x his taq, pET20b(+), the recombinant was transformed into E coli (strain DE3)
      and induced by IPTG. Recombinant vWF-A3 was designated as a recombinant fragment
      comprising residues 918 - 1114 of mature vWF subunit. It was purified through Ni
      NTA resin column and refolded in Tris buffer containing GSH and GSSG. The results
      showed that rvWF-A3 was expressed successfully in E coli (strain DE3), accounting
      for 46% of total bacterial protein with its purity of over 95%. It was identified
      that rvWF-A3 is capable to bind collagen and inhibit the wild vWF binding to
      collagen by competition. It is concluded that rvWF-A3 fragment might be an
      effective antithrombotic agent for preventing arterial thrombosis.

PMID- 15157334
TI  - [The diagnostic value of platelet glycoprotein-specific autoantibody detection in
      idiopathic thrombocytopenic purpura].
AB  - To detect levels of platelet glycoprotein-specific autoantibody in idiopathic
      thrombocytopenic purpura (ITP), chronic aplastic anemia (CAA), hematologic
      malignancies and healthy volunteers, and evaluate the clinical significance of
      platelet glycoprotein-specific autoantibody level in diagnosis for ITP, anti
      GPIb/IX, anti-GPIIb/IIIa, anti-GPIV and anti-GPV auto-antibodies were detected
      contemporaneously by a modified monoclonal antibody immobilization of platelet
      antigen assay (modified MAIPA). The results showed that the total positive rate
      of antibodies against platelet GPIb/IX, GPIIb/IIIa, GPIV, GPV were 69.99%, 10%,
      20% and 0% in ITP, CAA, hematologic malignancy group and healthy volunteers
      respectively. There was significant difference between ITP and CAA (chi(2) =
      20.71, P < 0.005), between ITP and hematologic malignancy group (chi(2) = 12.22,
      P < 0. 005). There was no positive finding in the healthy control. It is
      concluded that platelet glycoprotein-specific autoantibody has high value for the
      diagnosis of ITP,many kinds of antibodies detection at one time can enhance
      sensitivity, MAIPA is a specific assay for the diagnosis of idiopathic
      thrombocytopenic purpura.

PMID- 15157335
TI  - [The effects of mycophenolic acid on the maturation and immunologic function of
      murine bone marrow-derived dendritic cells].
AB  - Mycophenolate mofetil (MMF) is a newly developed immunosuppressor, widely used in
      allogeneic bone marrow transplant. The purpose of this study was to evaluate the
      effects of mycophenolic acid (MPA), the active metabolite of MMF in vivo, on the
      maturation and immunologic function of murine bone marrow-derived dendritic cells
      (DC), and to explore the underlying mechanisms of MMF in graft versus host
      disease. Cultured DC were treated with MPA at doses of 0.01 and 0.1 micro mol/L.
      The immunophenotype of DC in control and treated groups was analyzed by flow
      cytometry. The capability of antigen presentation and the stimulatory activity of
      the DC on allogeneic T cells were tested by incorporation of (3)H-TdR and mixed
      lymphocyte reaction respectively. IL-12 production in culture supernatant and the
      levels of Th1/Th2 cytokines such as IL-2, IFN-gamma, IL-4 and IL-10 in mixed
      lymphocyte reaction (MLR) supernatant were examined by ELISA assay. The results
      showed that DCs cultured in the presence of MPA expressed low levels of CD40,
      CD80 and CD86, and exhibited weak activity in stimulating the proliferation of
      allogeneic T cells and antigen presenting function with a concurrent reduction of
      IL-12 production. Allogeneic T cells stimulated by MPA-treated DC expressed
      higher levels of Th2 cytokines such as IL-4 and IL-10 but lower levels of Th1
      cytokines such as IL-2 and IFN-gamma than those stimulated by DC without MPA
      treatment. It is concluded that MPA, and hence MMF, exerts a negative effect on
      the maturation and immunologic functions of DC in culture, and drives a shift of
      Th1 to Th2 cytokines in MLR.

PMID- 15157336
TI  - [Preliminary in vitro study on modification of RBC with mPEG-BTC for resolving
      the problem of clinical difficulty in blood matching].
AB  - The aim of this study was to find an effective solution for difficulty of blood
      matching. Twenty nine cases with clinical difficult in blood matching were
      collected, classified by their etiological factors, and analyzed with all the
      antibodies in serum. RBC from health donor were incubated with mPEG-BTC at 25
      degrees C for 1 hour. The coagulation of patient serum and donor RBC before and
      after mPEG-BTC camouflage was detected and compared by polybrene and antihuman
      globulin reagents. The result showed that 29 cases with difficult blood matching
      mainly suffered form blood diseases and tumors. The main antibody were Rh and
      autoantibody. Donor RBC modified by mPEG showed no coagulation with the blood
      serum in the patients with problems of blood matching. In conclusion, the
      modification of RBC with mPEG-BTC provides a useful strategy for resolving
      problem of clinical difficulty in blood matching.

PMID- 15157337
TI  - [Determination and comparison of anti-SARS antibody in children and adults].
AB  - To investigate the positive rate of anti-SARS antibody in children and adults
      without SARS, 197 paediatric patients under 14 years old from inpatient and
      outpatient department of our hospital, 156 healthy children pupils from primary
      school, 453 adult patients over 18 years old from inpatient and outpatient
      department of our hospital and other 502 healthy adult blood donors were
      selected. Anti-SARS antibodies were determined by anti-SARS specific antibody
      detection kit and ELISA method. The results showed that both the positive rates
      of IgG antibody in paediatric patients and healthy children were about 2% (4/197
      and 3/156), while the positive rates in adult patients and healthy adults were
      about 0.2% (1/453 and 1/502). The difference between the positive rates of
      children and adults was significant (chi(2) = 11.61, P < 0.001). IgM antibody was
      negative in all the samples. It is concluded that the anti-SARS IgG antibody
      positive rate in children was obvious higher than that in adults. This may be the
      cause why the cases with SARS in children is much less than in adults.

PMID- 15157338
TI  - [Special morphological changes of pathologic cells in two cases of Waldenstrom's
      macroglobulinemia].
AB  - Waldenstrom's macroglobulinemia (WM) is one of malignant hematological disease on
      account of abnormal proliferation of B lymphocyte clone and the pathologic cells
      of WM possess ability to secrete monoclonal immunoglobulin M. In this study, the
      diagnosis and morphological characteristics of 2 patients with WM were analyzed.
      The results showed that a special kind of "foam cells" were found by cytochemical
      staining examinations in both cases, which displayed characteristics of
      lymphocytes, but neither monocyte-macrophage nor fatty cells. The periodic acid
      Shiff's reaction (PAS) demonstrated strong positive, especially on the inclusion
      bodies in pathologic cell plasma while the acid phosphatase, and alpha-butanoic
      acetate esterase stainings, resulted both in negative. In conclusion, the cells
      found in the two cases reported may be described as gemmy ring-like lymphocyte in
      morphology, a special subtype of ring-like lymphocyte.

PMID- 15157339
TI  - [Significance of detecting platelet associated antibody and platelet membrane
      glycoprotein for diagnosis of immune thrombocytopenia].
AB  - The aim of this study was to explore application value of detecting platelet
      associated antibody and platelet membrane glycoprotein in the diagnosis and
      prognosis for immune thrombocytopenia. The platelet associated immunoglobulin
      (PAIg) and platelet membrane glycoprotein (CD41, CD61, GPIIb/IIIa) in 76 cases of
      immune thrombocytopenia and 30 healthy subjects were determined by FCM. The
      results showed that PAIg level in ITP patients included PAIgG (31.25 +/- 18.06)%,
      PAIgM (32.41 +/- 15.51)%, PAIgA (23.39 +/- 16.67)% which were remarkedly higher
      than in health control (10.48 +/- 5.05)%, (9.40 +/- 4.42)% and (7.23 +/- 3.61)%
      (P < 0.001). In patients with secondary immune thrombocytopenia (chronic aplastic
      anemia, SLE, Evans syndrome, liver cirrhosis hypersplenism, etc), PAIg level was
      higher than that in control group, while the platelet membrane glycoprotein in
      the blood of these patients was lower than that in control group. The level of
      PAIg decreased (P < 0.05) after treatment, but platelet membrane glycoprotein
      increased (P < 0.01). The result suggested that measurements for platelet
      membrane glycoprotein and platelet associated antibody by FCM were practical with
      high sensitivity, rapidity and simplicity used as a routine method in diagnosis
      and evaluation of the therapeutic effects in immune thrombocytopenia patients.

PMID- 15157340
TI  - [Evaluation of bone marrow biopsy and smear examinations in differential
      diagnosis for patients with pancytopenia by simultaneously compartive study].
AB  - To simultaneously compare and evaluate the examinations of bone marrow smear and
      trephine biopsy in differential diagnosis and therapeutical effect of
      pancytopenia patients, the differences between bone marrow smear and trephine
      biopsy in degree of cellularity, misdiagnosis rate and therapeutical effect for
      71 patients with pancytopenia were analyzed. The results showed that the degree
      of cellularity in bone marrow biopsy for cytologic morphology was higher than
      that from the smear, but misdiagnosis rate in the biopsy was lower than that in
      the smear. In conclusion, bone marrow biopsy is necessary to the differential
      diagnosis and more valuable for evaluation of therapeutical effect and prognosis
      of pancytopenia patients.

PMID- 15157341
TI  - [Progress of research on protein composition and gene therapy of Fanconi anaemia 
      review].
AB  - Fanconi anaemia (FA) is an autosomal recessive inherited disorder caused by
      defects in hematopoietic stem cells. The clinical manifestations of FA are
      diverse and complicated. FA cells display high hypersensitivity to agents which
      produce interstrand DNA cross-links such as mitomycin C (MMC) or diepoxybutane
      (DEB). At least eight complementation groups with defects in eight genes (FANCA,
      FANCB, FANCC, FANCD(1), FANCD(2), FANCE, FANCF and FANCG) have been identified by
      gene analysis. Six genes (corresponding to subtypes A, C, D(2), E, F and G) have
      been coloned, and the encoded FA proteins interact in a common cellular pathway -
      "FA Pathway", through which modulate DNA repair. The progress of research on FA
      molecular mechanism provides gene therapy of FA with theory basis. FA cells
      transduced with the use of retrovirus carring the normal FA gene cDNA manifestate
      phenotypic correction of hypersensitivity to DNA cross-linking agents, such as
      MMC. In this review the clinical manifestations and gene composition of FA, and
      the functions of encoded FA proteins were summarized. The hematopoietic stem cell
      transplantation and gene therapy for FA patients were discussed.

PMID- 15157342
TI  - Killer cell inhibitory receptors involved in graft-versus-host disease and graft
      versus-leukemia effect in allogeneic hematopoietic stem cell transplantation -
      review.
AB  - Killer cell inhibitory receptors (KIR) are members of the immunoglobulin
      superfamily (Ig-SF) and transmembrane molecules type I expressed on human natural
      killer cells and some T lymphocytes. They are ligands for HLA class I antigens.
      According to the "missing-self" hypothesis, KIR deliver inhibitory signals that
      prevent target-cell lysis upon binding to the self MHC class I antigens. KIR
      regulates NK cell function concerned with the control graft-versus-host disease
      (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem
      cell transplantation (HSCT). The KIR repertoire is substantially influenced by
      the polymorphic and polygeneic nature of the KIR gene family, and there exist the
      polymorphism of KIR ligands mainly HLA-C molecule. So it is difficult to achieve
      the beneficial effect of NK cells on the outcome of partly HLA-mismatched
      hematopoietic cell transplantation. This review aims to provide background and
      previous observations on the KIRs which are thought to influence the outcome of
      HSCT.

PMID- 15157343
TI  - [Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy -
      review].
AB  - Tumor antigen-specific cytotoxic T lymphocytes are important anti-cancer cells.
      The focuses of this review are to introduce the molecular basis of antigen
      presentation and CTL recognition, to summarize the identification of tumor
      associated antigens and their T cell epitopes, to highlight the current insights
      into the immunogenicity of TAA peptides and the principles of peptide-based
      vaccines against cancer, and to comment on future prospects for CTL therapy.

PMID- 15157345
TI  - Risperidone is effective for wandering and disturbed sleep/wake patterns in
      Alzheimer's disease.
AB  - Behavioral and psychological symptoms of dementia (BPSD), especially
      aggressiveness, wandering, and sleep disturbance, are a major burden for
      caregivers. Daily sleep/wake patterns and wandering of institutionalized patients
      with Alzheimer's disease (AD) were visually monitored, and 34 patients who
      manifested wandering were selected and randomly classified into 2 groups: the
      risperidone group and the nonrisperidone group. After an administration of low
      dose risperidone for the risperidone group, the BPSD were reassessed. The binding
      potentials of dopamine D2 receptor for preadministration and postadministration
      of risperidone were assessed using positron emission tomography (PET) for 1 case.
      After the use of risperidone, aggressiveness and wandering were reduced and the
      nighttime sleeping hours were increased. The PET revealed that the binding
      potential of dopamine receptor was increased after administration of the drug,
      associated with improved sleep/wake patterns and behavioral abnormality. Possible
      serotonergic modulation of dopaminergic function might explain the
      neurobiological basis of the effect of risperidone.

PMID- 15157344
TI  - How does an Alzheimer's disease patient's role in medical decision making change
      over time?
AB  - As persons with Alzheimer's disease (AD) lose their ability to make decisions,
      someone else has to make decisions for them. We performed a prospective cohort
      study of 77 AD patient-caregiver dyads to examine when this transition occurs.
      When dementia severity surpassed a threshold marked by a Mini-Mental State
      Examination (MMSE) score less than 20, the level of caregiver-reported patient
      involvement in the medical decision-making process declined (Moderate [MMSE = 19
      12]: Odds Ratio [OR] = 2.35, 95% confidence interval [95% CI] = 1.01-5.49; P
      =.048; Severe [MMSE < 12]: OR = 29.38, 95% CI = 5.98-144.25, P <.001).
      Furthermore, older patients (OR = 1.06, 95% CI = 1.00-1.12, P =.049) and mounting
      caregiver burden (OR = 1.12, 95% CI = 1.04-1.26, P =.003) were significant
      independent predictors of transitions to the caregiver-dominated medical decision
      making process. These results provide clinicians with prognostic information that
      can help caregivers understand how their role in decision making will change over
      the course of a patient's dementing illness.

PMID- 15157346
TI  - The frequency of executive cognitive impairment in elderly rehabilitation
      inpatients.
AB  - The aim of this study was to determine the frequency of executive cognitive
      dysfunction in a sample of elderly patients in 2 rehabilitation wards in
      Wellington, New Zealand. All patients in 2 wards over a 2-month period were
      approached and invited to complete a brief neuropsychological battery. Sixty-two
      patients volunteered, of whom 52 completed at least 3 of the 4 measures of
      executive functioning. The frequency of executive dysfunction in the resulting
      sample of 52 was determined. Impaired executive function was defined as impaired
      performance on at least 2 executive function tests. The authors administered the
      Hayling-Brixton tests, the verbal fluency test, the Trail-Making Test, the Mini
      Mental State Examination (MMSE), and the Geriatric Depression Scale. Patients'
      behavior was rated for executive problems on the Dysexecutive Questionnaire by
      themselves and by a nurse. The frequency of executive impairment was high at 13
      out of 52 patients (25%). Only 1 of these 13 patients with executive difficulties
      was impaired according to their MMSE score. Screening for executive impairment
      among older rehabilitation inpatients is a necessary part of their medical
      management and rehabilitation. This should involve more than just administering
      the MMSE at admission. Several brief methods for screening for executive
      impairment are now available.

PMID- 15157347
TI  - Clock Drawing Test-Modified and Integrated Approach (CDT-MIA): description and
      preliminary examination of its validity and reliability in dementia patients
      referred to a specialized psychogeriatric setting.
AB  - The authors developed a scoring system for clock drawing, based on modification
      and integration of 3 established scoring methods. The Clock Drawing Test-Modified
      and Integrated Approach (CDT-MIA) is a 4-step, 20-item instrument, with a maximum
      score of 33, which emphasizes differential scoring of contour, numbers, hands,
      and center. It was administered to 139 patients (93 with and 46 without
      dementia). Dementia patients revealed significantly more impairment on the CDT
      MIA total score and hours and hands subscores. Correlations between CDT-MIA and 2
      CDTs were high. With receiver operating characteristics (ROC) curves, the area
      constructed under CDT-MIA curve was large. The best trade-off between sensitivity
      and specificity for CDT-MIA was the cut-point 23 (91% and 80%, respectively). The
      internal consistency of CDT-MIA was high, and there was a high degree of
      interrater reliability. Thus, CDT-MIA was found to be a valid and reliable
      evaluation instrument for dementia patients in a specialized setting.

PMID- 15157348
TI  - Validation of a 26-point telephone version of the Mini-Mental State Examination.
AB  - The objective of this study was to assess the convergent validity of a 26-point
      Telephone Mini-Mental State Examination (MMSE) in a longitudinal cohort of 46
      Alzheimer's disease (AD) patients. Paired in-person and telephone MMSE
      observations were collected within 35 days of each other. The setting was the
      Stanford/VA Alzheimer's Center in Palo Alto, California, and patients'
      residences. The 30-point Folstein MMSE was administered in-person, and a 26-point
      telephone version of the MMSE, adapted from the Adult Lifestyles and Function
      Interview (ALFI)-MMSE. Total scores for the in-person and telephone MMSE versions
      correlated strongly (Pearson's r =.88, P <.001). Hearing impairment and education
      level did not significantly affect telephone-based performance. The Telephone
      MMSE can be used to validly estimate in-person MMSE scores of patients with AD.
      Use of this practical measure can enhance reassessment if returning to the clinic
      is difficult or if a change in the patient's medical condition merits a check of
      mental status by telephone.

PMID- 15157349
TI  - Depressive symptoms and bone mineral density in older men.
AB  - Most studies examining the relation between depression and bone mineral density
      (BMD) have been limited to psychiatric patients or to community-dwelling, older
      women. We conducted a cross-sectional and prospective cohort study to determine
      whether depressive symptoms are associated with low BMD in community-dwelling,
      older men. We recruited 515 men 50 years of age or older from population-based
      listings of age-eligible men. Participants completed the Geriatric Depression
      Scale (short form) and were considered depressed if they scored 6 or more out of
      15 possible points. BMD was measured in the spine and hip using dual energy x-ray
      absorptiometry in all participants, and again an average of 3.6 years later in a
      random subset of 100 participants. The prevalence of depressive symptoms (GDS =
      6) was 3.1% (16 of 515). We found no difference in mean BMD or mean percent
      change in BMD per year of the hip and lumbar spine in men who had 6 or more
      depressive symptoms compared with men who reported 5 or fewer symptoms of
      depression. These findings suggest that depressive symptoms are not associated
      with BMD in community-dwelling, older men.

PMID- 15157350
TI  - The relationship between functional disability and depressive mood in Japanese
      older adult inpatients.
AB  - Depression is commonly found in older adult patients and is often associated with
      handicaps. The authors administered the Comprehensive Geriatric Assessment (CGA),
      including basic activities of daily living (BADL), instrumental activities of
      daily living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression
      Scale (GDS)-15, and a socioenvironmental questionnaire to 198 patients who were
      admitted to Nagoya University Hospital, to examine the relationship between
      depressive mood and various physical and socioenvironmental outcomes. The overall
      GDS-15 score was correlated with the BADL and IADL. The factor analysis extracted
      4 factors from the GDS-15 subscales. The factors labeled "loss of morale and
      hope" and "memory loss and reduction of social activity" were highly correlated
      with both ADLs, social variables, and the MMSE score. The results reveal that
      factor analysis of GDS-15 will help in understanding the etiology of depressive
      mood, thereby contributing to better therapeutic approaches.

PMID- 15157351
TI  - Treatment effects from UPBEAT: a randomized trial of care management for
      behavioral health problems in hospitalized elderly patients.
AB  - The purpose of this study was to examine the impact of the Unified
      Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) Program, an
      interdisciplinary mental health care management program, on the behavioral health
      symptoms of elderly veterans. Participants, 60 years and older, included 2637
      veterans recruited from medical/surgical units who screened positively for
      significant depressive or anxiety symptoms and/or at-risk alcohol drinking.
      Participants were randomized to UPBEAT or to usual care. Primary outcomes were
      measured at baseline and at 6, 12, and 24 months. Participant nonadherence to the
      protocol was common and is a major limitation. There were no differences between
      UPBEAT and usual care patients on symptom or functional outcomes at any follow-up
      point. Exploratory analyses suggested that among participants with more physical
      health problems, there were greater improvements in depressive symptoms in those
      assigned to UPBEAT care. Despite a theoretical and practically sound
      intervention, participation was low and treatment outcomes, while generally good,
      appeared unaffected by the addition of the program.

PMID- 15157352
TI  - HIV type 1 transmission by human bite.

PMID- 15157353
TI  - Hepatitis C virus (HCV) relapses after anti-HCV therapy are more frequent in HIV
      infected patients.
AB  - The response to standard or pegylated interferon (IFN) plus ribavirin (RBV) seems
      to be lower in hepatitis C virus (HCV)/HIV-coinfected subjects than in HCV
      monoinfected patients. Thus, the principles guiding anti-HCV therapy in HIV
      negative patients may not apply in the setting of HIV infection. We examined the
      rate of HCV relapse in 58 HCV/HIV-coinfected subjects who showed undetectable HCV
      RNA (<600 IU/ml) at the end of anti-HCV combination therapy. Overall, 19 (32.8%)
      patients relapsed after discontinuing treatment, a rate significantly higher than
      that seen in HIV negatives, which is in the range of 15-20%. There were no
      significant differences between HCV genotypes (33.3% for HCV genotypes 2-3 versus
      31.8% for HCV genotypes 1-4) and/or the use of either standard or pegylated IFN
      (37% versus 29%, respectively). Thus, extended periods of anti-HCV therapy might
      reduce HCV relapses in HIV-coinfected patients initially responding to therapy.

PMID- 15157354
TI  - High prevalence of antiretroviral resistance in treated Ugandans infected with
      non-subtype B human immunodeficiency virus type 1.
AB  - This study examined the emergence and prevalence of drug-resistant mutations in
      reverse transcriptase and protease coding regions in human immunodeficiency virus
      type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV).
      Genotypic resistance testing was performed on 50 and 16 participants who were
      enrolled in a cross-sectional and longitudinal observational cohort,
      respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as
      subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV
      experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations
      or more in reverse transcriptase. Resistance mutations in protease were less
      prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon
      sample collection. Mutations conferring drug resistance were also selected in 3
      of 16 participants in the longitudinal cohort, i.e., less than 8 months after the
      initiation of ARV treatment. Rapid emergence of ARV resistance was associated
      with poor adherence to treatment regimens, which was related to treatment costs.
      ARV resistance did, however, appear at a slightly higher prevalence in HIV-1
      subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this
      observational study suggests that ARV-resistant HIV-1 isolates are emerging
      rapidly in ARV-treated individual in Uganda and possibly other developing
      countries.

PMID- 15157355
TI  - Disease progression in heterosexual patients infected with closely related
      subtype B strains of HIV type 1 with differing coreceptor usage properties.
AB  - Previously we described a heterosexual outbreak of HIV-1 subtype B in a town in
      the north of England (Doncaster) where 11 of 13 infections were shown to be
      linked by phylogenetic analysis of the env gp120 region. The 11 infections were
      related to a putative index case, Don1, and further divided into two groups based
      on the patients' disease status, their viral sequences, and other epidemiological
      information. Here we describe two further findings. First, we found that viral
      isolates and gp120 recombinant viruses derived from patients from one group used
      the CCR5 coreceptor, whereas viruses from the other group could use both the CCR5
      and CXCR4 coreceptors. Patients with the X4/R5 dual tropic strains were
      symptomatic when diagnosed and progressed rapidly, in contrast to the other
      patient group that has remained asymptomatic, implying a link between the tropism
      of the strains and disease outcome. Second, we present additional sequence data
      derived from the index case, demonstrating the presence of sequences from both
      clades, with an average interclade distance of 9.56%, providing direct evidence
      of a genetic link between these two groups. This new study shows that Don1
      harbored both strains, implying he was either dually infected or that over time
      intrahost diversification from the R5 to R5/X4 phenotype occurred. These events
      may account for/have led to the spread of two genetically related strains with
      different pathogenic properties within the same heterosexual community.

PMID- 15157357
TI  - When integrated in a subepithelial mucosal layer equivalent, dendritic cells keep
      their immature stage and their ability to replicate type R5 HIV type 1 strains in
      the absence of T cell subsets.
AB  - Many potential targets of human immunodeficiency virus type 1 (HIV-1) reside in
      the human reproductive tract, including dendritic cells (DC). The ability of
      these cells to replicate HIV-1 is dependent on many factors such as their
      differentiation/maturation stage. Nevertheless, precise mechanisms underlying the
      early steps of transmucosal infection are still unknown. Our purpose was to
      investigate DC/HIV-1 interactions in a subepithelial mucosal layer equivalent
      (SEMLE) reconstructed in vitro. We used mixed interstitial DC (IntDC)/Langerhans
      cell (LC)-like cell subpopulations generated in vitro from CD34(+) progenitors.
      These cells were either integrated in SEMLE or maintained in suspension.
      Experimental infections were performed with a type X4 strain (HIV-1(LAI)) and a
      type R5 strain (HIV-1(Ba-L)). Proviral DNA was detected by in situ polymerase
      chain reaction (PCR) and viral replication was quantified by measuring p24 core
      protein release in the culture media. Our results showed that SEMLE enable DC to
      retain immature stage and reproduce the tropic selection that occurs in vivo.
      Indeed, IntDC/LC were infected by both types of HIV-1 strains, regardless of the
      infection schedule, whereas only type R5 virus replicated in DC in the absence of
      T cell subsets. Furthermore, the ability of DC to replicate HIV-1(BaL) was lost
      after 14 days of culture unless the cells had previously been integrated in
      SEMLE. These results suggest that this 3D model maintains the ability of DC to
      replicate type R5 virus by delaying their maturation. In conclusion, this in
      vitro model mimics human submucosa and can be considered as relevant for studying
      the preliminary steps of transmucosal HIV-1 infection.

PMID- 15157356
TI  - HIV type 1 that select tRNA(His) or tRNA(Lys1,2) as primers for reverse
      transcription exhibit different infectivities in peripheral blood mononuclear
      cells.
AB  - The replication in human peripheral blood mononuclear cells (PBMC) of unique HIV
      1 that select tRNA(His) or tRNA(Lys1,2) for reverse transcription was compared to
      the wild-type virus that uses tRNA(Lys,3). HIV-1 with only the primer-binding
      site (PBS) changed to be complementary to these alternative tRNAs initially
      replicated more slowly than the wild-type virus in PBMC, although all viruses
      eventually reached equivalent growth as measured by p24 antigen. Viruses with
      only a PBS complementary to the 3' terminal 18 nucleotides of tRNA(His) or
      tRNA(Lys1,2) reverted to use tRNA(Lys3). HIV-1 with mutations in the U5-PBS to
      allow selection of tRNA(His) and tRNA(Lys1,2) following long-term growth in SupT1
      cells were also evaluated for growth and PBS stability following replication in
      PBMC. Although both viruses initially grew slower than wild type, they maintained
      a PBS complementary to the starting tRNA and did not revert to the wild-type PBS
      after long-term culture in PBMC. Analysis of the U5-PBS regions following long
      term culture in PBMC also revealed few changes from the starting sequences. The
      virus that stably used tRNA(His) was less infectious than the wild type. In
      contrast, the virus that stably used tRNA(Lys1,2) evolved to be as infectious as
      wild-type virus following extended culture in PBMC. The results of these studies
      highlight the impact of the host cell on the tRNA primer selection process and
      subsequent infectivity of HIV-1.

PMID- 15157358
TI  - Interactions of processed Nef (58-206) with virion proteins of HIV type 1.
AB  - The Nef protein plays a major role in vivo in promoting HIV and SIV replication
      and pathogenesis. In vitro, Nef has been shown to down-regulate cell surface
      molecules, such as CD4 and MHC-I, alter T cell signaling, and enhance virion
      infectivity. These effects are attributed to interactions of Nef with cellular
      proteins. In addition, HIV Nef is incorporated into viral particles, mainly
      localizing in the virion cores. However, no report has been published to date
      regarding Nef interactions with virion proteins. By immunoprecipitation, Nef was
      found to bind to viral enzymes. Using yeast two-hybrid and GST pulldown
      procedures to find out direct potential partners of Nef, Nef was consistently
      found to interact with viral integrase (IN). The interaction between Nef and IN
      was stronger when Nef was present as the viral protease-cleaved isoform. We
      hypothesize that the interaction of Nef with viral integrase or other virion
      proteins may explain the presence of Nef in viral cores. In addition, this
      interaction suggests that Nef may accompany the reverse transcription and the
      preintegration complexes during the early steps of the infection cycle and
      potentially affect infectivity during these steps.

PMID- 15157359
TI  - Analysis of full-length HIV type 1 env genes indicates differences between the
      virus infecting T cells and dendritic cells in peripheral blood of infected
      patients.
AB  - Dendritic cells (DC) are targets for HIV-1 infection and may harbor distinct
      populations of virus variants. To test this hypothesis full length env genes have
      been amplified and sequenced from DC and T cells purified from the blood of five
      symptomatic HIV-1-infected patients. For three of the patients, showing slow and
      slow/standard disease progression, distinct subsets of HIV variants infected DC
      and T cells, and the diversity of the DC-derived env genes was less than that
      observed in T cells. Amino acid substitutions differentiating DC and T cell
      variants were dispersed throughout the length of the glycoproteins and were
      patient/HIV-1 strain specific. However, the V1 and V2 domains of T cell-derived
      clones were generally shorter than those from DC. These findings suggest that
      there may be distinct populations of HIV-1 variants infecting blood DC and T
      cells in patients showing slow and slow/standard disease progression.

PMID- 15157360
TI  - Simultaneous presence of endogenous retrovirus and herpes virus antigens has
      profound effect on cell-mediated immune responses: implications for multiple
      sclerosis.
AB  - Retroviruses have been suggested as possible pathogenic factors in multiple
      sclerosis (MS), supported by the observation that endogenous retroviruses are
      activated in MS patients. Different members of the herpes family of which several
      are neurotropic have also been suggested as factors in MS pathogenesis. Further,
      interactions between retroviruses and herpes viruses have been implied in the
      development of MS. The objective of the study was investigation of cell-mediated
      immune responses of MS patients to retrovirus and herpes virus antigens,
      particularly antigen combinations, with analyses of the influence of retrovirus
      antigens on cellular immunological reactivity toward other viral antigens.
      Cellular immunity as measured by blast transformation assays was analyzed using
      freshly isolated peripheral blood mononuclear cells from 47 MS patients and 36
      healthy volunteers. Combinations of the endogenous retrovirus HERV-H and herpes
      virus antigens resulted in highly increased cellular immune responses among both
      the MS patients and healthy subjects. The increase was synergistic in character
      in most samples. Very pronounced effects were obtained using HHV-6A and HSV-1
      antigens. Blast transformation assays combining antigens from two different
      herpes viruses or combinations of measles and herpes antigens showed no synergy.
      The obtained data indicate a pronounced synergistic effect on the cellular immune
      response when retrovirus and herpes antigens are present together. The cause of
      the synergy is unknown so far. The effect on the immune response may influence
      the disease progression.

PMID- 15157362
TI  - Native HIV type 1 virion surface structures: relationships between antibody
      binding and neutralization or lessons from the viral capture assay.
AB  - Despite a vigorous antibody response following HIV-1 infection, antibodies which
      neutralize primary isolates tend to be of low titer or sporadic. Similarly,
      antibodies produced in response to HIV-1 vaccines in human and animals react with
      HIV but, only on occasion, do these antibodies neutralize primary isolates. The
      failure of the immune system to respond in an effective manner is related to the
      inherent structural properties of the HIV-1 envelope expressed on the native
      virion and the pathogenesis of HIV infection. Identification of effective
      antibody interactions with HIV, as judged by inhibition of virus, is crucial for
      the development of broadly effective HIV vaccines and immune therapeutics. It has
      been proposed that antibodies must bind and neutralize virus to be effective at
      controlling HIV infection. We propose that this hypothesis may limit the
      identification of effective antibodies that are desperately needed given the
      difficulty in preventing and treating HIV. We provide evidence that the viral
      capture assay (VCA) is an important adjunct to the study of antibody interactions
      with primary isolate virus. Further, we propose that antibodies that are
      ineffective in traditional neutralization assays may also be effective at
      limiting viral spread and preventing viral infection.

PMID- 15157361
TI  - Protective immunity to SIV challenge elicited by vaccination of macaques with
      multigenic DNA vaccines producing virus-like particles.
AB  - We utilized SIV(mne) infection of Macaca fascicularis to assess the efficacy of
      DNA vaccination alone, and as a priming agent in combination with subunit protein
      boosts. All SIV(mne) structural and regulatory genes were expressed using the
      human cytomegalovirus Immediate Early-1 promoter in plasmids that directed the
      formation of virus-like particles in vitro. Macaques (n = 4) were immunized
      intradermally and intramuscularly four times over 36 weeks with 3 mg plasmid DNA.
      A second group (n = 4) received two DNA priming inoculations followed by two
      intramuscular boosts consisting of 250 microg recombinant Env gp160 and 250
      microg recombinant Gag-Pol particles in MF-59 adjuvant. These regimens elicited
      modest cellular immunity prior to challenge. Humoral immune responses to Env
      gp160 were elicited and sustained by both vaccine protocols, and as expected
      antibody titers were higher in the protein subunit-boosted animals. Neutralizing
      antibodies prior to challenge were measurable in two of four subunit-boosted
      macaques. The two vaccine regimens elicited comparable helper T cell responses at
      the time of challenge. Vaccinees and mock-immunized controls (n = 4) were
      challenged intrarectally at week 38 with uncloned SIV(mne). Following challenge
      all macaques became infected, but both vaccine regimens resulted in reduced peak
      virus loads (p = 0.07) and significantly improved maintenance of peripheral
      CD4(+) T cell counts postchallenge (p = 0.007, DNA alone and p = 0.01, all
      vaccinees). There was no significant difference between the two vaccine groups in
      levels of plasma viremia or maintenance of CD4(+) T cell counts postchallenge.

PMID- 15157363
TI  - Immune responses to HTLV-I(ACH) during acute infection of pig-tailed macaques.
AB  - Human T cell lymphotropic virus type 1 (HTLV-I) is causally linked to adult T
      cell leukemia/lymphoma (ATL) and a chronic progressive neurological disease, HTLV
      I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A nonhuman
      primate model that reproduces disease symptoms seen in HTLV-I-infected humans
      might facilitate identification of initial immune responses to the virus and an
      understanding of pathogenic mechanisms in HTLV-I-related disease. Previously, we
      showed that infection of pig-tailed macaques with HTLV-I(ACH) is associated with
      multiple signs of disease characteristic of both HAM/TSP and ATL. We report here
      that within the first few weeks after HTLV-I(ACH) infection of pig-tailed
      macaques, serum concentrations of interferon (IFN)-alpha increased and
      interleukin-12 decreased transiently, levels of nitric oxide were elevated, and
      activation of CD4(+) and CD8(+) lymphocytes and CD16(+) natural killer cells in
      peripheral blood were observed. HTLV-I(ACH) infection elicited virus-specific
      antibodies in all four animals within 4 to 6 weeks; however, Tax-specific
      lymphoproliferative responses were not detected until 25-29 weeks after infection
      in all four macaques. IFN-gamma production by peripheral blood cells stimulated
      with a Tax or Gag peptide was detected to varying degrees in all four animals by
      ELISPOT assay. Peripheral blood lymphocytes from one animal that developed only a
      marginal antigen-specific cellular response were unresponsive to mitogen
      stimulation during the last few weeks preceding its death from a rapidly
      progressive disease syndrome associated with HTLV-I(ACH) infection of pig-tailed
      macaques. The results show that during the first few months after HTLV-I(ACH)
      infection, activation of both innate and adaptive immunity, limited virus
      specific cellular responses, sustained immune system activation, and, in some
      cases, immunodeficiency were evident. Thus, this animal model might be valuable
      for understanding early stages of infection and causes of immune system
      dysregulation in HTLV-I-infected humans.

PMID- 15157364
TI  - Touching the void--taking decisions and finding solutions.

PMID- 15157365
TI  - Enuresis in children and young people: a public health nurse approach in New
      Zealand.
AB  - The involuntary passing of urine at age six and older is called enuresis. Wetting
      during the day is called diurnal enuresis and wetting at night while asleep is
      called nocturnal enuresis. Nocturnal enuresis is second only to allergy as the
      commonest chronic disorder in childhood. Many children (adolescents are included
      in the term 'children') who are nocturnal enuretics exhibit behaviours such as
      low self-esteem, withdrawal, less ambition and increased anxiety. These children
      are often low achievers within the school system and become a problem for their
      family and school. In this article the author discusses a child/adolescent
      centred primary nocturnal enuresis program and service that is administered by a
      group of public health nurses in South Auckland, New Zealand.

PMID- 15157366
TI  - Improving transition: a qualitative study examining the attitudes of young people
      with chronic illness transferring to adult care.
AB  - Transition is a process that attends to the medical, psychosocial and educational
      needs of young people as they transfer to adult-orientated care. With a growing
      population of adolescents surviving with chronic illness well into adulthood, it
      is remarkable that empirical research has paid little attention to transition.
      This qualitative study examined the attitudes of young people with chronic
      illness who were facing transition, considering what young people wanted from a
      transition service and the ways in which provision could be improved from a
      service-user's perspective. A purposive sample of seven adolescents (aged 14-17)
      attending a hospital youth club were interviewed. To increase the likelihood of
      successful transition, strategies need to be informal, flexible, highly
      individualized and prepare adolescents steadily for adult services.

PMID- 15157367
TI  - An initial evaluation of the design of pediatric psychology consultation service
      with children with diabetes.
AB  - The objective of this study was to review the process of psychology consultation
      with an outpatient pediatric diabetes service, and provide data regarding
      assessment and outcome. The purpose was to demonstrate that the inclusion of
      psychology in the care of the child would enhance the effectiveness of treatment
      delivery. Over a one-year period, 91 psychological consultations were reviewed
      for information related to reasons for referral, diagnosis, and treatment.
      Processes of assessment and collaboration are described. Nearly half of all the
      participants that were referred for a consultation met the criteria for a
      psychiatric disorder, including Attention-Deficit Hyperactivity Disorder, mood
      disorder or anxiety. Paired t-tests revealed significant improvement in metabolic
      control from referral to the next clinic appointment. Psychological consultation
      appears to have a positive impact on selected health outcomes. Given the large
      number of children with psychiatric disorder, psychological intervention may
      facilitate adherence and reduce complications associated with poor metabolic
      control.

PMID- 15157368
TI  - The family life-path theory: a tool for nurses working in partnership with
      families.
AB  - The purpose of this article is to describe the family life-path theory. The
      theory may offer nurses an alternative model for use in working in partnership
      with the family of a child with a long-term illness. It is important that nurses
      have a deep understanding of a family's everyday life. The better nurses know the
      family and the context in which it lives, the more individual advice and coping
      strategies that they are able to find in partnership with a family, and thus to
      support the family in achieving a good quality of life. The theory describes the
      life of a family of a child with asthma as a lifepath. The dimensions of the
      family's life-path are environment, the child's becoming ill, the family's view
      of health, their attitude towards illness, everyday routines and social network.
      The unpredictability of asthma, optimism about the future and normalization of
      life are factors that guide families towards achievement of a good quality of
      life for their child.

PMID- 15157369
TI  - Bone marrow transplantation from a parental perspective.
AB  - The present study focuses on the parents of the first group of children in Sweden
      to receive a bone marrow transplant and survive. Its aim was to get in-depth
      knowledge of the parents' situation during this critical time. The result of 10
      years of research (1988-98), the study deals with the situation to which the
      parents had to adapt and the strategies that they used to handle their situation
      within a long-term perspective. Two series of qualitative interviews with the
      parents of 20 children who had undergone bone marrow transplantation were carried
      out. A self-report questionnaire for coping was also used. The result shows that
      the child's illness and treatment played an important role in the parents' lives
      for many years. Those parents who managed to put reason before emotion rated
      their coping as better. A sense of participation was also a useful coping
      strategy.

PMID- 15157370
TI  - Health needs of young offenders.
AB  - Health services' input to the Youth Offending Teams (YOTs) is an integral
      component of the YOTs' philosophy. Fifty young people aged 14-18 years, who
      attended two representative YOTs consecutively, completed a health checklist and
      a strengths and difficulties questionnaire. They were interviewed on the health
      of the nation outcome scales for children and adolescents and their perceptions
      of health needs and services. The young people reported high rates of accidents
      and injuries, admissions to hospital, emotional and peer relationships
      difficulties. Their perceptions of what mental illness means varied between
      stigma, aggression, lack of coping, previous experiences and physical ill-health.
      Only five young people expressed a wish to receive mental health help. The
      findings are discussed in relation to health services provision to the YOTs.

PMID- 15157372
TI  - At the crossroads of evolutionary computation and music: self-programming
      synthesizers, swarm orchestras and the origins of melody.
AB  - This paper introduces three approaches to using Evolutionary Computation (EC) in
      Music (namely, engineering, creative and musicological approaches) and discusses
      examples of representative systems that have been developed within the last
      decade, with emphasis on more recent and innovative works. We begin by reviewing
      engineering applications of EC in Music Technology such as Genetic Algorithms and
      Cellular Automata sound synthesis, followed by an introduction to applications
      where EC has been used to generate musical compositions. Next, we introduce
      ongoing research into EC models to study the origins of music and detail our own
      research work on modelling the evolution of melody.

PMID- 15157371
TI  - Children with specific language impairment: parental accounts of the early years.
AB  - Parent views of specific language impairment have received little attention in
      the literature, even though speech and language development is the single
      greatest area of concern for parents. This article examines parental views of
      events up to, and including, language unit admission for their children. A series
      of qualitative interviews was conducted with parents. Parents felt that, apart
      from speech and language difficulties, the children were developing normally.
      They placed a low value on speech and language therapy, and saw language unit
      admission as the only intervention that 'worked'. Initially, some children were
      placed in mainstream school, where their failure to keep up with peers resulted
      in transfer to a language unit. Parent views provide a unique understanding of
      the impact of specific language impairment on the child and family. Such
      information is essential for the early diagnosis and treatment of this condition.

PMID- 15157373
TI  - Ideal evaluation from coevolution.
AB  - In many problems of interest, performance can be evaluated using tests, such as
      examples in concept learning, test points in function approximation, and
      opponents in game-playing. Evaluation on all tests is often infeasible.
      Identification of an accurate evaluation or fitness function is a difficult
      problem in itself, and approximations are likely to introduce human biases into
      the search process. Coevolution evolves the set of tests used for evaluation, but
      has so far often led to inaccurate evaluation. We show that for any set of
      learners, a Complete Evaluation Set can be determined that provides ideal
      evaluation as specified by Evolutionary Multi-Objective Optimization. This
      provides a principled approach to evaluation in coevolution, and thereby brings
      automatic ideal evaluation within reach. The Complete Evaluation Set is of
      manageable size, and progress towards it can be accurately measured. Based on
      this observation, an algorithm named DELPHI is developed. The algorithm is tested
      on problems likely to permit progress on only a subset of the underlying
      objectives. Where all comparison methods result in overspecialization, the
      proposed method and a variant achieve sustained progress in all underlying
      objectives. These findings demonstrate that ideal evaluation may be approximated
      by practical algorithms, and that accurate evaluation for test-based problems is
      possible even when the underlying objectives of a problem are unknown.

PMID- 15157374
TI  - Combating coevolutionary disengagement by reducing parasite virulence.
AB  - While standard evolutionary algorithms employ a static, absolute fitness metric,
      coevolutionary algorithms assess individuals by their performance relative to
      populations of opponents that are themselves evolving. Although this arrangement
      offers the possibility of avoiding long-standing difficulties such as premature
      convergence, it suffers from its own unique problems, cycling, over-focusing and
      disengagement. Here, we introduce a novel technique for dealing with the third
      and least explored of these problems. Inspired by studies of natural host
      parasite systems, we show that disengagement can be avoided by selecting for
      individuals that exhibit reduced levels of "virulence", rather than maximum
      ability to defeat coevolutionary adversaries. Experiments in both simple and
      complex domains are used to explain how this counterintuitive approach may be
      used to improve the success of coevolutionary algorithms.

PMID- 15157375
TI  - Dynamic subset selection based on a fitness case topology.
AB  - A large training set of fitness cases can critically slow down genetic
      programming, if no appropriate subset selection method is applied. Such a method
      allows an individual to be evaluated on a smaller subset of fitness cases. In
      this paper we suggest a new subset selection method that takes the problem
      structure into account, while being problem independent at the same time. In
      order to achieve this, information about the problem structure is acquired during
      evolutionary search by creating a topology (relationship) on the set of fitness
      cases. The topology is induced by individuals of the evolving population. This is
      done by increasing the strength of the relation between two fitness cases, if an
      individual of the population is able to solve both of them. Our new topology
      based subset selection method chooses a subset, such that fitness cases in this
      subset are as distantly related as is possible with respect to the induced
      topology. We compare topology-based selection of fitness cases with dynamic
      subset selection and stochastic subset sampling on four different problems. On
      average, runs with topology-based selection show faster progress than the others.

PMID- 15157376
TI  - [Bring the long-time EEG monitoring into play in diagnosis of childhood
      epilepsy].

PMID- 15157377
TI  - [Oral aspirin caused Reye's syndrome in a child].

PMID- 15157378
TI  - [Raise the diagnosis level of attention deficit hyperactivity disorder in
      children].

PMID- 15157379
TI  - [Pay enough attention to human infection with avian influenza virus].

PMID- 15157380
TI  - [The 7th National Conference of Pediatric Hepatology was held in Chongqing].

PMID- 15157381
TI  - [Diagnosis of childhood narcolepsy and significance of HLA in its diagnosis].
AB  - OBJECTIVE: Narcolepsy is a lifelong sleep disorder characterized by excessive
      daytime sleepiness, and features of rapid eye movement (REM) sleep, such as
      cataplexy, sleep paralysis and hypnagogic hallucinations. The present study aimed
      to investigate the diagnostic basis of childhood narcolepsy and possible role of
      HLA Class II alleles in the onset of this disease. METHODS: The clinical data of
      40 narcoleptic children were analyzed. All patients received Multiple Sleep
      Latency Test (MSLT) and they were analyzed in combination with clinical features.
      Polymerase chain reaction/sequence specific primers (PCR/SSP) methods were used
      to detect the HLA-DRB1 and DQB1 alleles. RESULTS: Narcolepsy was diagnosed in 40
      children. The age range was 3 to 14 years (mean 8.5 +/- 2.5 years), 29 were male
      and 11 female. Their mean course of disease was 6.5 months, 14 patients (30%)
      were less than 3 months old, 21 patients (52%) were less than 6 months old. All
      the patients had excessive daytime sleepiness, cataplexy appeared in 37 cases,
      hypnagogic hallucination in 22 and sleep paralysis in 6. Mean sleep latency on
      MSLT was less than 5 min, the average number of sleep-onset rapid eye movement
      (SOREM) was 4.33 +/- 0.26 episodes (2-5 episodes), the latency of SOREM episodes
      were 4.0 +/- 1.8 min (0.25-4.9 min). Thirty-five patients were DRB1 1501 and DQB1
      0602 positive (Pc < 0.01), 2 were DRB1 1502 and DQB1 0601 positive, while 3 were
      DRB1 15 and DQB1 6 negative. CONCLUSIONS: Some pediatric patients with narcolepsy
      were different from adult patients in that the pediatric cases had a sudden onset
      and shorter disease course. Diagnosis of this disease was based on the clinical
      manifestations, MSLT and absence of any medical or psychiatric disorder that
      could account for the symptoms. The authors demonstrated that DRB1 1501 and DQB1
      0602 were susceptibility genes for narcolepsy and those who were DRB1 15 negative
      could not be excluded.

PMID- 15157382
TI  - [Clinical feature of Rett syndrome and MeCP2 genotype/phenotype correlation
      analysis].
AB  - OBJECTIVE: Rett syndrome (RTT) is a neurodevelopmental disorder which causes
      severe mental retardation. This study aimed at elucidating clinical features of
      66 Chinese RTT cases diagnosed by The Department of Pediatric Neurology, Peking
      University First Hospital since 1987, and at analysis of the MeCP2 genotype /
      phenotype correlation. METHODS: Sixty-six RTT cases were followed up every one to
      two years to get the information of their clinical manifestations and the
      response to the L-carnitine treatment which was administered to the patients at a
      dose of 80-100 mg/(kg d). MeCP2 mutation analysis by PCR and sequencing were
      performed on 39 cases. RESULTS: In this cohort of cases, the onset of the disease
      occurred between 3 and 38 months of age, 89% of the cases lost their purposeful
      hand use at 7 months to six years of age, all the cases had stereotype hand
      movement which presented at 1 to 5 years of age, 85% of the cases lost language
      ability at 11 months to eight years of age, 21% of the cases lost the ability of
      walking at ages of 2 years and 9 months to 15 years. The symptoms/signs such as
      small head circumference, seizures, breathing irregularities, teeth grinding,
      scoliosis/ kyphosis were presented in many of the cases. The clinical
      manifestations were improved in 6 cases after L-carnitine treatment. MeCP2 gene
      mutation was found in 64% of the cases. Two cases with non-sense mutation C502t
      (amino acid change R168X) died, two cases with missense mutation C397T (amino
      acid change R133C) and one case with missense mutation A398T (amino acid change
      R133H) preserved several words. CONCLUSION: Deceleration of the head growth, loss
      of acquired purposeful hand use, stereotype hand movement and language
      deterioration were the main characteristics of RTT. L-carnitine could improve the
      clinical manifestation of some cases. There are some correlations between MeCP2
      genotype and phenotype.

PMID- 15157383
TI  - [Myasthenia gravis in children: clinical study of 77 patients].
AB  - OBJECTIVE: To study the clinical characteristics of myasthenia gravis (MG) in
      children and the changes in AchR-Ab-seronegative (SNMG) MG and AchR-Ab
      seropositive MG (SPMG) patients. METHODS: The study was done on 77 MG patients
      who were diagnosed at The Pediatric Hospital, Fudan University from 1992 to 2002.
      This clinical trial was a non-randomized, controlled open study. RESULTS: (1) The
      age of onset ranged from 3 months to 16 years, and the most common ages of onset
      were before 3 years; 32 cases were males and 45 females. The extraocular muscles
      were more frequently involved. According to the modified Osserman's criteria, 54
      patients (70%) were classified as type I, 21 cases (27%) as type II and 2 cases
      (3%) as type III. (2) Eighteen of 55 cases (35%) were positive for anti
      acetylcholine receptor antibodies (AchRab) and 16 of 55 cases (31%) were positive
      for acetylcholine premembrane receptor antibody (PremRab) on the initial
      examination. The clinical state of the patient during the examination did not
      show any clear correlation with the level of these antibodies. There was no
      significant difference between clinical type and AchRab positive rate among the
      three groups. Two of 18 patients (11%) were positive for thymoma associated
      antibody (Tintinab). The serological test on follow-up showed that 6 of 10 SNMG
      cases (60%) turned to be SPMG. In 85% of the cases the results of CD cells
      examination was abnormal, most of them showed reduced levels of CD4(+) or CD3(+)
      and CD8(+). (3) The thymus proliferation was found in 22 patients (42%) by CT and
      changes of thymoma were found in 2 cases (4%) and were confirmed by operation.
      (4) In 50% of the cases the electromyography (EMG) was abnormal. (5) After
      anticholinesterase drugs and steroids treatment the prognosis of patients with MG
      was usually good. CONCLUSIONS: MG in our children's hospital has increased, the
      age of onset became younger, and type II MG cases increased. Seronegative
      patients could turn positive, so monitoring the patient's serology is helpful for
      finding more SPMG cases. Steroids have been proven effective and safe in
      treatment of MG in children. Patients in methylprednisolone group experienced
      less side effects of steroid therapy than group treated with oral prednisone.

PMID- 15157384
TI  - [Neuroprotective effect of naloxone in brain damage caused by repeated febrile
      seizure].
AB  - OBJECTIVE: The brain damage caused by repeated febrile seizure (FS) during
      developing age is harmful to the intellectual development of children. So how to
      decrease the related damage is a very important issue. The main purpose of the
      present study was to find out whether the non-specific opiate antagonist naloxone
      at low dose has the neuroprotective effect on seizure-induced brain damage.
      METHODS: Warm water induced rat FS model was developed in this study. Forty-seven
      rats were randomly divided into two groups: normal control group (n = 10) and
      hyperthermic seizure groups (n = 37). The latter was further divided into FS
      control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone
      is different in two naloxone-treated groups (12/each group), in one group the
      dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced
      in each rat of hyperthermic seizure groups with the interval of 2 days. The rats
      were weighed and injected intraperitoneally with naloxone once the FS occurred in
      naloxone-treated group, while the rats of the other groups were injected with
      0.9% sodium chloride. Latency, duration and grade of FS in different groups were
      observed and compared. HE-staining and the electron microscopy (EM) were used to
      detect the morphologic and ultrastructural changes of hippocampal neurons.
      RESULTS: In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/-
      0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P
      < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49),
      although no significant gap was observed on FS latency between them. In FS
      control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of
      disordered neurons with confused polarity and vacuoles formed. Nuclei were with
      various size, some rounded and some oblong. While in naloxone-treated groups, the
      arrangement of neurons was regular, only a small quantity of neurons had changed
      polarity and vacuoles formed. Most nuclei were oblong and in the same size. In
      hippocampal CA(1) region and dentate gyrus of rats from FS control group, EM
      showed that the most mitochondrion volumes obviously increased with vacuoles
      formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body
      emerged. Minor to moderate dilation of rough endoplasmic reticulum and Golgi's
      complex was also observed. However, in naloxone-treated groups, the number of
      neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than
      that in FS control group. No apoptosis body was observed. The comparison between
      them showed much lighter brain damage in naloxone-treated groups than in FS
      control group. CONCLUSION: Although low-dose naloxone could not totally stop the
      occurrence of febrile seizure, it could lighten the brain damage resulted from
      repeated FS to some extent.

PMID- 15157385
TI  - [Suggestions for rational use of electroencephalography in pediatrics].

PMID- 15157386
TI  - [Summary of the National Conference on Epilepsy and the 10th Symposium on
      Pediatric Neurology].

PMID- 15157387
TI  - [Reactivity and antigenic cross-reactivity of latex in children with allergic
      disorders].
AB  - OBJECTIVE: To explore the relationship between latex allergen and clinical
      presentation as well as allergenic cross-reactivity between latex and other
      allergens, to know the incidence of latex allergy in Chinese children and
      elucidate the allergenic cross-reactivity of latex with other allergens. METHODS:
      Totally 265 children with allergic disorders were assayed with 13 international
      standard allergen agents by means of SPT. RESULTS: In 79 children with latex
      allergenic SPT position, 53 were boys and 26 were girls with an average age of
      5.6 years, and 14 cases had episodes occurred in winter, 14 cases in spring, 24
      cases in summer, and 27 cases in autumn. Of them, 66 cases presented as asthma, 5
      cases atopic skin disorders, 1 case anaphylactoid purpura, 1 case hives and 6
      cases only had mild cough. Statistical analysis showed that the positive
      percentage of the latex SPT had no obvious relation with sex and age, but was
      higher in summers and autumns than in winters and springs (P < 0.01). Children
      with allergic symptoms had higher positive rate in latex allergenic SPT than
      those without them, that is, the positive percentage of the latex SPT
      significantly increased among children presenting with some allergic symptoms,
      such as asthma, hives and atopic skin disorders (P < 0.01). All the children with
      latex allergenic SPT position had cross-reactivity with acarid allergen, 62.0%
      approximately 43.0% with animal protein allergens including milk, cats, shrimp,
      dogs, eggs in the order of decreasing cross-reaction rate, and 10.1% - 3.8% with
      mold and plant farina allergens. But the cross-reactivity between latex and mold
      or tree farina I were not statistically significant. CONCLUSION: Thirty percent
      of the children with allergic disorders were latex allergenic SPT positive. Latex
      allergenic SPT positive results were significantly correlative to allergic
      clinical presentation and season, while were not relative to sex and age. The
      cross-reactivity of latex with acarid was most common, followed by animal protein
      allergens, while the cross-reactivity with mold and plant farina allergen was
      rare.

PMID- 15157388
TI  - [Relativity of nuclear factor-kappaB (P65/Rel-A) and angiotensin II type 1
      receptor expression in early stage of lesions of adriamycin nephrosis in young
      rats and the effects of intervention].
AB  - OBJECTIVE: To investigate the trend and potential pathogenic role of nuclear
      factor (NF)-kappaB P(65)/Rel-A mRNA and angiotensin-II (AngII) receptor type 1
      (AT(1)) proteins expression, and the relativity between them in early stage of
      renal tubulointerstitial lesions in young rats with adriamycin nephrosis and the
      interfering effects of treatment with angiotensin converting enzyme inhibitor
      (ACEI) benazepril and ACEI combined with AngII type 1 receptor antagonist
      (AT(1)RA) Losartan. METHODS: Male young Wistar rats with adriamycin nephrosis
      were used as experimental models. At different time points (weeks 1, 2, and 3 in
      early nephritic phase, the urinary protein and blood biochemical parameters were
      measured, and P(65)/Rel-A mRNA was detected; AT(1) protein expression was
      determined by in situ hybridization and immunohistochemical methods. The
      relativity between them was evaluated. RESULTS: In the early phase of
      tubulointerstitial lesions, following adriamycin injection and proteinuria
      aggravated progressively, at week 3, the proteinuria level had reached heavy
      proteinuria (123.2 +/- 7.7 mg/24 h). The serum parameters reflecting renal
      function were elevated. The inflammatory cells infiltrated into renal tissues,
      especially in tubulointerstitial regions, were increased markedly. Swelling of
      tubular epithelial cells, broadened tubulointerstitial areas, and protein casts
      in tubule were observed. In situ hybridization and immunochemical staining showed
      that AT(1) protein was expressed in tubular epithelial cell cytoplasm and on
      nuclear membranes (AT(1): 1st week 19.8 +/- 1.1%, 2nd week 25.0 +/- 2.6%, 3rd
      week 37.1 +/- 1.0% (control: 10.3 +/- 0.8%, 10.4 +/- 1.6%, 10.2 +/- 1.5%); and
      P(65)/Rel-A mRNA expression in the same locations was upregulated. P(65)/Rel-A
      translocation from cytoplasm into nucleus increased markedly simultaneously. The
      positive signal of hybridization dominated in cytoplasm gradually became dominant
      in the nuclei as the pathological changes progressed. The semiquantitative
      expression of P(65)/Rel-A was 24.0 +/- 3.3% at week 1, 34.2 +/- 2.4% at week 2,
      39.9 +/- 6.4% at week 3, while the values of controls were 8.5 +/- 0.4%, 8.7 +/-
      1.0%, and 8.4 +/- 0.9%, respectively. There was a positive correlation between
      AT(1) and P(65)/Rel-A expression in localization and time phase (r = 0.857, P <
      0.01). However, the tendency of those factor's expression was all decreased in
      each treated group, the semiquantitative results were AT(1): 14.6 +/- 2.1%, 13.7
      +/- 2.3%, 11.4 +/- 1.1%; P(65)/Rel-A: 18.5 +/- 3.4%, 22.8 +/- 1.6%, 26.7 +/- 4.9%
      at 1, 2, 3 weeks in ACEI treated group; AT(1): 12.4 +/- 1.5%, 11.1 +/- 1.0%, 10.3
      +/- 0.8%; P(65)/Rel-A: 17.9 +/- 5.0%, 21.3 +/- 6.0%, 22.5 +/- 2.5% in AT(1)RA
      (Losartan) group, respectively. The significant difference were observed between
      all groups in different time points (P < 0.05). CONCLUSIONS: The present study
      suggested that NF-kappaB (P(65)/Rel-A) mRNA expression and its activity was
      enhanced significantly that synchronized with aggravating injures in
      tubulointerstitial lesions initial period induced by proteinuria-loading in
      nephrotic young rats. This tendency was related with AngII and its receptors
      system that may accelerate lesions progressing in many renal diseases.

PMID- 15157390
TI  - [Changes of sleep architecture in children with obstructive sleep apnea
      syndrome].
AB  - OBJECTIVE: To explore how obstructive sleep apnea syndrome (OSAS) affects
      children's sleep architecture. METHODS: Eighty-three children with OSAS were
      reviewed; every patient was monitored with polysommography for 7 hours at night
      for 11 parameters, including the number of arousal, snoring index, nadir O(2)
      desaturation, stage I %, stage II %, show wave sleep (SWS)% and rapid eye
      movement (REM)%. The basis for diagnosis of OSAS was the widely accepted
      pediatric diagnostic criteria of apnea/hypopnea index, apnea/ hypopnea index of >
      1 episode/hour, nadir O(2) desaturation < 92%. Sleep was scored manually
      according to the standard set by Rechtschaffen. RESULTS: In OSAS group, the
      number of arousal was 22.5 +/- 1.4, snoring index was 70.6 +/- 16.5, and/or
      SaO(2) was (73.8 +/- 1.9)%. OSAS group had increased stage I : (45.8 +/- 2.0)%
      vs. (2.3 +/- 1.1)%, t = 22.46, P < 0.01 and decreased stage II : (23.9 = 1.7)% vs
      (47.9 = 4.4)%, t = - 14.18, P < 0.01, SWS (15.6 +/- 1.8)% vs. (21.1 +/- 5.0)%, t
      = - 3.123, P < 0.01, REM (14.7 +/- 1.5)% VS. (28.2 +/- 4.1)%, T = -8.923, p <
      0.01. CONCLUSION: The severity of OSAS relates to changes of sleep architecture
      in children. Intermittent nocturnal hypoxia secondary to apnea/hypopnea, and
      frequent electroencephalogram arousals from sleep may result in significant sleep
      fragmentation. Children with OSAS had learning problems and failure to thrive.

PMID- 15157389
TI  - [Medically unexplained dyspnea in children: a review of 34 cases].
AB  - OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14%
      patients complaining of dyspnea. Its occurrence in children is seldom recognized.
      In the present paper, 34 children with medically unexplained dyspnea (age 10 to
      18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are
      reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical:
      it was based on the presence of dyspnea and other complaints which cannot be
      explained by an organic disease. The patients answered Nijmegen questionnaire and
      state and trait anxiety (STAI), and performed hyperventilation provocation test.
      Twenty sessions of breathing therapy were applied and 13 out of 34 children were
      followed up after the therapy. RESULTS: Among the children, 75% started to have
      symptoms at the age of 13 to 16 years, though the age of first episode could be
      as early as 8 years. In most of the cases, the course was chronic clinically. In
      addition to marked dyspnea, their clinical profile included symptoms of
      hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm.
      The symptoms of anxiety were less frequent in children and accordingly the level
      of anxiety evaluated by means of STAI was lower in children compared to adult
      patients. The precipitating psychological factors appeared to be related to
      middle school competition. Pressure from exams, reprimand from stern and
      unsympathetic teachers coupled with high parental expectation could be
      emotionally damaging to psychologically susceptible children. Thirteen patients
      were followed up after 2-3 months of breathing therapy with emphasis on abdominal
      breathing and slowing down of expiration. After therapy, the sum score of the
      Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of
      hyperventilation were improved. The level of anxiety was minimally modified.
      CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and
      treatment because of the high rate of chronicity of the disorder.

PMID- 15157392
TI  - [Transcatheter closure of secundum atrial septal defect in children].
AB  - OBJECTIVE: This study was undertaken to investigate the indication, methodology
      and complication of transcatheter closure of secundum atrial septal defect (ASD).
      ASD transcatheter occlusion techniques have become alternative to surgical
      procedures. A number of different devices are available for transcatheter ASD
      closure. The type and incidence of complications depend partially upon different
      devices. METHODS: A retrospective analysis was performed on the patients treated
      from October 1998 to January 2003. Transcatheter closure of ASD with Amplatzer
      septal occluder (ASO) was performed in 119 patients, of whom 3 patients were
      multiple ASD, 3 associated with pulmonary stenosis (PS) and 3 patent ductus
      arteriosus (PDA). The age of the cases ranged from 0.8 to 17 years (mean 7.5 +/-
      2.8 years) and the body weight ranged from 6.7 to 88 kg (mean 23.7 +/- 7.8 kg).
      They all met with criteria for transcatheter closure. The balloon-stretched
      diameter of ASD was determined with fluoroscopy, ultrasound and measuring plate.
      A choice of device size was identical to or 1 approximately 2 mm larger than the
      stretched diameter (SD). A simultaneous PDA closure with device or balloon
      dilation was done in six cases associated with PDA or PS, respectively. Follow-up
      was performed based on the echocardiographic and clinical findings. RESULTS: In
      119 cases examined with transesophageal echocardiography (TEE) or trans-thoracic
      echocardiography (TTE), ASD mean diameter was (12.9 +/- 5.6) mm (6.5 - 34.5 mm),
      pulmonary mean pressure was (29.0 +/- 5.0) mmHg (25.0 - 62.0 mmHg), and SD was
      (15.7 +/- 4.8) mm (8.0 - 38.0 mm). The diameters of these devices were (15.0 +/-
      5.0) mm (8 - 38 mm). The devices were successfully implanted in 112 cases. Of
      them, 3 patients had multiple ASD with one device occlusion. 6 cases associated
      with PDA or PS were treated successfully with PDA occlusion or balloon
      dilatation, respectively. The immediate, one month and one year complete
      occlusion rates were 93.8% (105/112), 97.3% (109/112) and 98.2% (110/112),
      respectively. Residual shunt remained in 2 cases. No complication occurred except
      transient atrial premature beats and grade II type 1 A-V block in 5 cases (4.5%)
      and 1 cases (0.9%), respectively. The whole time period of the procedure ranged
      from 25 to 68 minutes. The total follow up period was from one month to 4.3
      years. No unsatisfactory device position or embolization or clinical evidence of
      bacterial arteritis was found during the follow-up period. CONCLUSION:
      Transcatheter closure of secundum ASD using the ASO is a safe and effective
      alternative to surgical repair. Transcatheter closure of secundum ASD associated
      with small anterior, inferior or posterior rim is feasible using ASO. ASO can be
      performed in infants and young children only if the diameter of disk is smaller
      than the diameter of atrial septum. Multiple ASD is not the contraindication for
      intervention. If the diameter of ASD is over 36 mm, the device choice should
      depend on the maximum diameter of ASD determined with echocardiography. TTE is
      suitable for the smaller ASD and TEE for the bigger ASD. It is very important to
      avoid air embolism and atrial perforation during the procedure.

PMID- 15157391
TI  - [Two cases of Askin tumor misdiagnosed as pulmonary tuberculosis].

PMID- 15157393
TI  - [Radiofrequency catheter ablation of septum originated tachycardia in children].
AB  - OBJECTIVE: The study was undertaken to analyze retrospectively the results of
      radiofrequency catheter ablation (RFCA) on septum originated tachycardia in
      children with arrhythmia. The 98 children were all treated with RFCA on septum
      originated tachycardia in which the ablation sites were located near the bundle
      of His. METHODS: Fifty female and forty-eight male cases were included in this
      analysis. They were at the age of 8.1 +/- 2.3 years and their body weight was (28
      +/- 9) kg. The arrhythmia they suffered from consisted of atrioventricular nodal
      reentry tachycardia (AVNRT) (n = 62), atrioventricular reentry tachycardia (AVRT)
      on septum (n = 25), atria Itachycardia on Koch areas (n = 3) and left ventricular
      tachycardia (ILVT) on the septum (n = 8). Swartz SRO long sheath was used on the
      right site ablation. Titration of capacity and degreed time of increase were used
      in the ablation. RESULTS: Radiofrequency ablation was successful in all cases.
      Eleven cases had relapse after the procedure. They accepted RFCA again and then
      the treatment succeeded. One case of AVRT at the posterior septum experienced
      complete atrioventricular block (AVB) during ablation. Two weeks later this case
      was implanted with permanent pacemaker. CONCLUSIONS: The septal site is narrow
      and small in children. Atrioventricular node is tender. If the above facts were
      neglected, it was very likely to cause AVB, especially in children accepting the
      procedures of electrophysiologic study an RFCA on the septal site. Attention
      should be paid to the followings during such procedures: ablation in the sinus
      rhythm; ablation following the principle, titration of capacity and degreed time
      of increase; ablation at the right site long sheath; thermo-ablation catheter
      application and ablation on the two sides of septum in the posterior septum
      ablation procedure. The end-point of ablation in children should be the
      elimination of tachycardia and the delta wave, disassociation of VA or passing
      through bundle of His at pacing in the ventricle, disappearance of jumping
      conduction or no echo or one echo but without AVNRT after infusion of
      isoprenaline and stimulation procedure. Avoiding bundle of His injury is
      important during the procedure of ablation in children.

PMID- 15157395
TI  - [Continuous intravenous infusion of midazolam for treatment of status epilepticus
      in children].

PMID- 15157394
TI  - [CD25 monoclonal antibody for GVHD prophylaxis in non-T-cell depleted
      haploidentical bone marrow transplantation for treatment of childhood leukemia].
AB  - OBJECTIVE: Allogeneic bone marrow transplantation (Allo-BMT) has improved long
      term survival in children patients with refractory leukemia. For patients who do
      not have an HLA-identical sibling, the treatment option is limited. Using related
      mismatch donors or parental donors for Allo-BMT was at high risk for acute severe
      GVHD. The purpose of this study was to explore the effects of CD25 monoclonal
      antibody on reducing the incidence of severe acute GVHD in haploidentical bone
      marrow transplantation for the treatment of childhood leukemia. METHODS: Ten
      children with leukemia received haplotype Allo-BMT from HLA two or three loci
      mismatched related donors. Most patients were classified as in high risk
      category. The donors of patients were given G-CSF (Lenograstim Chugai) 250
      microg/day for seven doses prior to marrow harvest. The non-T-cell depleted
      haploidentical bone marrow was infused. In addition to combination of CSA, MTX,
      ATG (Fresenius Hemocare, Germany) and mycophenolate mofetil (MMF) for GVHD
      prophylaxis, CD(25) monoclonal antibody (Simulect, Novartis Pharma Switzerland)
      was administered to prevent acute severe GVHD.A total of 40 mg Simulect was given
      in two doses of 20 mg each by 30 min intravenous infusion 2 h before
      transplantation and day 4 after transplantation. The outcomes were compared with
      those of 8 children patients with leukemia who received haploidentical bone
      marrow transplantation without CD(25) antibody for GVHD prophylaxis. RESULTS: All
      patients were engrafted and sustained full donor-type engraftment. 100% donors
      hematopoietic cells after transplantation was determined by cytogenetic evidence
      analysis. The median days of granulocyte exceeding 0.5 x 10(9)/L and pallets
      exceeding 20 x 10(9)/L were 19 and 22 days, respectively. Patients were monitored
      till up to days 100 for the sign of aGVHD. None developed the grade II-IV acute
      GVHD. However, the incidence of the grade II-IV acute GVHD in control group was
      50% (P = 0.0147). Eight patients could be evaluated for chronic GVHD. All
      experienced chronic GVHD confined to the skin. The median follow-up duration was
      12 months (range 9 - 24 months). Two patients died from transplant related
      mortality, one had patient relapsed disease and died. The remaining seven
      patients were alive in disease-free situation. CONCLUSION: The use of Simulect in
      haploidentical bone marrow transplantation for the treatment of children patients
      with leukemia is effective for preventing acute severe GVHD and may reduce
      transplant-related mortality.

PMID- 15157396
TI  - [Evaluation of inhalation therapy with pediatric asthma quality of life
      questionnaire in children with asthma].

PMID- 15157397
TI  - [Present status of studies on neural stem cells transplantation in newborn
      animals and for ischemic brain injuries].

PMID- 15157398
TI  - [A case of chronic inflammatory demyelination polyradiculopathy related to
      Campylobacter jejuni infection in human and animals].

PMID- 15157399
TI  - [Present status of studies on avian influenza and human infection with avian
      influenza virus].

PMID- 15157400
TI  - [Progresses in studies on residual cardiovascular problems in children with
      postoperative tetralogy of Fallot].

PMID- 15157401
TI  - [Significance of autoantibodies in rheumatic diseases].

PMID- 15157402
TI  - [A case of variant childhood benign Rolandic epilepsy].

PMID- 15157403
TI  - [Airway obstruction at several sites caused severe obstructive sleep apnea with
      hypopnea syndrome in a child].

PMID- 15157404
TI  - Low-Grade Gliomas in Adults.
AB  - Adult patients with a magnetic resonance scan suggestive of a supratentorial low
      grade glioma should generally undergo at least a stereotactic biopsy to confirm
      the diagnosis and rule out an anaplastic glioma or a non-neoplastic lesion. Early
      tumor treatment should be given to patients with newly diagnosed low-grade
      gliomas who are over age 50 years, those who have headaches or neurologic
      deficits other than seizures, or those whose neuroimaging studies show tumor
      growth or mass effect. For younger patients presenting with seizures and no other
      neurologic symptoms, it is reasonable to defer therapy until there is clinical or
      radiographic tumor progression. When it is judged that intervention is necessary,
      patients should undergo the maximal surgical tumor resection, which preserves or
      improves neurologic function. For younger (<50 years) astrocytoma patients with a
      good tumor resection, radiation may be deferred until tumor progression. Early
      radiation should be given to astrocytoma patients who are older than 50 years of
      age at diagnosis (regardless of the type of surgery) or to younger patients who
      are judged to require early intervention but who are not candidates for
      aggressive surgical resection. The radiation dose for low-grade glioma should be
      4500 to 5000 cGy, preferably with three-dimensional conformal ports. The same
      guidelines for management apply to patients with low-grade oligodendroglioma or
      oligoastrocytoma, except that chemotherapy is a reasonable alternative to
      radiation when it is judged that treatment other than surgical resection is
      required.

PMID- 15157405
TI  - Management of Brain Metastases.
AB  - Advances in neurosurgery and the development of stereotactic radiosurgery have
      expanded treatment options available for patients with brain metastases. However,
      despite several randomized clinical trials and multiple uncontrolled studies,
      there is not a uniform consensus on the best treatment strategy for all patients
      with brain metastases. The heterogeneity of this patient population in terms of
      functional status, types of underlying cancers, status of systemic disease
      control, and number and location of brain metastases make such consensus
      difficult. Nevertheless, in certain situations, there is Class I evidence that
      supports one approach or another. The primary objectives in the management of
      this patient population include improved duration and quality of survival. Very
      few patients achieve long-term survival after the diagnosis of a brain
      metastasis.

PMID- 15157407
TI  - Intracerebral Meningiomas.
AB  - Meningiomas are extra-axial brain tumors of middle to late adult life, and they
      have a female predominance. Overall, 90% of meningiomas are benign, 6% are
      atypical, and 2% are malignant. Most patients diagnosed with a meningioma decide
      to have it removed surgically and are advised to do so based on their neurologic
      symptoms. Complete surgical resection is usually curative. For incompletely
      resected or recurrent tumors not previously irradiated, radiotherapy is
      administered. Radiotherapy may be administered as conventional external beam
      irradiation or stereotactically. Stereotactic radiotherapy, as linear accelerator
      or gamma-knife radiosurgery is increasingly used. Advocates of stereotactic
      radiotherapy have suggested this therapy in lieu of surgery particularly for poor
      surgical risk patients, patients with meningiomas in eloquent or surgically
      inaccessible locations, and patients of advanced age. When the meningioma is
      unresectable or all other treatments (surgery, radiotherapy) have failed,
      immunochemotherapy may be considered. Hydroxyurea, interferon-alpha, tamoxifen,
      and mifepristone have been modestly successful in patients with recurrent
      meningiomas, whereas cyclophosphamide, adriamycin, and vincristine,
      ifosfamide/mesna, or adriamycin/dacarbazine have been administered to patients
      with aggressive or malignant meningiomas.

PMID- 15157406
TI  - Epidural Spinal Cord Compression.
AB  - Epidural spinal cord compression is a neurologic emergency requiring immediate
      attention. The therapy instituted depends on several factors, including the
      patient's condition at the time of presentation, the nature of the underlying
      malignancy, the extent of systemic disease burden, and patient prognosis. The
      most essential aspect of treatment is the establishment of the diagnosis. If one
      suspects malignant cord compression an emergency, magnetic resonance imaging of
      the entire spinal axis is indicated. If magnetic resonance imaging is
      unavailable, post-myelographic computed tomography is an alternative. However,
      treatment should not be delayed until imaging is performed, particularly if
      neurologic deficits are present. Pain should be adequately addressed and opioids
      administered if necessary. Steroids should be given. If significant neurologic
      deficits are present, a high-dose corticosteroid bolus, followed by standing
      doses, should be given. However, if pain is the predominant symptom, steroids can
      be withheld pending immediate imaging or lower doses can be given without a
      bolus. Neurosurgical consultation should be obtained, and surgery should be
      considered if the patient's condition permits. This is particularly true if
      spinal instability or significant kyphosis is present or compression is secondary
      to bony fragments. Other indications include patients with limited systemic
      disease burden in whom better survival is predicted and possibly those with
      radioresistant tumors. The type of surgery performed should be tailored to the
      distribution of disease within the spine and accessibility through anterior body
      cavities. Radiation therapy, an effective noninvasive treatment that can be
      delivered quickly and safely, is an appropriate option as well. This is
      particularly true in radio-responsive tumors, such as myeloma and lymphoma, in
      which surgery may be avoided entirely. Chemotherapy may play a role as adjuvant
      therapy in some tumors.

PMID- 15157408
TI  - Obstructive Sleep Apnea.
AB  - Obstructive sleep apnea (OSA) is a major public health problem in the US that
      afflicts at least 2% to 4% of middle-aged Americans and incurs an estimated
      annual cost of 3.4 billion dollars. At Stanford, we utilize a multispecialty team
      approach combining the expertise of sleep medicine specialists (adult and
      pediatric), maxillofacial and ear, nose, and throat surgeons, and orthodontists
      to determine the most appropriate therapy for complicated OSA patients. The major
      treatment modality for children with OSA is tonsillectomy and adenoidectomy with
      or without radiofrequency treatment of the nasal inferior turbinate. Children
      with craniofacial anomalies resulting in maxillary or mandibular insufficiency
      may benefit from palatal expansion or more invasive maxillary/mandibular surgery.
      Continuous positive airway pressure (PAP) therapy is used in children with OSA
      who are not surgical candidates or have failed surgery. As a last resort,
      tracheotomy may be used in patients with persistent or severe OSA who do not
      respond to other measures. The cornerstone of treatment in adults utilizes PAP:
      continuous PAP, bilevel PAP, or auto PAP. Treatment of nasal obstruction,
      appropriate titration, attention to mask-fit issues, desensitization for
      claustrophobia, use of heated humidification for nasal dryness and nasal pain
      with continuous PAP, patient education, regular follow-up, use of compliance
      software (in selected individuals), and referral to support groups (AWAKE) are
      measures that can improve patient compliance. Adjunctive treatment modalities
      include lifestyle/behavioral/pharmacologic measures. Oral appliances can be used
      in patients with symptomatic mild sleep apnea or upper airway resistance
      syndrome. Patients who are unwilling or unable to tolerate continuous PAP or who
      have obvious upper airway obstruction may benefit from surgery. Surgical success
      depends on appropriate patient selection, the procedure performed, and the
      experience of the surgeon. Phase I surgeries have a success rate of 50% to 60%,
      whereas phase II surgeries have a success rate greater than 90%.

PMID- 15157409
TI  - Sleep Problems Across the Life Cycle in Women.
AB  - Across the life cycle of women, the quality and quantity of sleep can be markedly
      impacted by internal (eg, hormonal changes and vasomotor symptoms) and external
      (financial and child-care responsibilities; marital issue) factors. This paper
      will outline some of the major phases of the life cycle in women that have been
      associated with sleep problems. The main messages from this paper include 1) that
      very little systematic, large-scale research has been performed in virtually
      every area reviewed; and 2) once identified, the sleep problem is generally best
      addressed by the standard therapeutic approach, except in the case of pregnant
      and lactating women in which concern for the fetus and child must be considered
      in the treatment decision. This paper is organized into sections that address
      sleep problems associated with the menstrual cycle, pregnancy, postpartum, and
      perimenopause. Anecdotal reports recommend treatment that addresses the specific
      physical discomfort experienced by the woman (eg, analgesics for premenstrual
      pain, pregnancy pillows for backache, and hormone replacement therapy for hot
      flashes). The importance of developing standard treatment recommendations is
      stressed because the development of chronic insomnia has been linked to
      precipitating events. In addition, primary sleep disorders (eg, sleep apnea or
      restless legs syndrome) have been shown to increase during pregnancy and
      menopause, but treatment recommendations may be contraindicated or are not
      specific for women.

PMID- 15157410
TI  - Non-Rapid Eye Movement Parasomnias.
AB  - Non-rapid eye movement parasomnias are unique physical or experiential phenomena
      that disrupt sleep. Non-rapid eye movement parasomnias are common in children,
      but they typically outgrow them. Sleep-stage shifts caused by sleep-disordered
      breathing and associated arousals may be precipitating events for episodes of
      parasomnia. Seizure disorders should always be considered in the differential
      diagnosis for the evaluation of parasomnias. Violent or injurious sleepwalking
      should be rapidly evaluated and treated.

PMID- 15157411
TI  - Sleep, Sleep Apnea, and Epilepsy.
AB  - Sleep disorders occur commonly in patients with epilepsy, and can be responsible
      for symptoms of daytime somnolence and also can contribute to the intractability
      of epilepsy. The most important aspect of treating sleep disorders, especially
      sleep apnea, is the recognition of the problem. In a busy clinical practice,
      symptoms of sleep disorders are frequently overlooked or mistaken. Whenever sleep
      disruption or excessive daytime somnolence is potentially problematic, the
      patient should be referred to a sleep specialist and, if indicated, diagnostic
      testing performed (usually polysomnography with or without multiple sleep latency
      tests). The author also recommends that all patients receive basic counseling
      about sleep hygiene, because its principles are often helpful to patients in
      general. Even in the absence of a sleep disorder, the choice of an anticonvulsant
      can be partly tailored to the sleep needs of the patient, with alerting drugs
      (lamotrigine and felbamate) dosed early in the day and relatively sedating agents
      (phenobarbital and phenytoin) dosed later or at bedtime.

PMID- 15157412
TI  - Silence sets on a sensory map.
AB  - Recent efforts to understand the contribution of neuronal activity in the
      creation of the olfactory sensory map have focused on odor-evoked events. In this
      issue of Neuron, Yu et al. discover a new role for neuronal activity in the
      organization and maintenance of the olfactory system. Their results highlight the
      role of spontaneous activity and synaptic transmission in axon outgrowth and
      olfactory neuron survival.

PMID- 15157414
TI  - Splitting the spotlight of visual attention.
AB  - Can the brain attend to more than a single location at one time? In this issue of
      Neuron, McMains and Somers report psychophysical and fMRI evidence showing that
      subjects can attend to two separate locations concurrently and that divided
      spatial attention leads to separate zones of attentional enhancement in early
      visual cortex.

PMID- 15157413
TI  - Selective dopamine filter of glutamate striatal afferents.
AB  - Corticostriatal glutamate afferents and mesostriatal dopamine afferents commonly
      converge onto the same postsynaptic spines of medium projection neurons. The
      consequent synaptic triad provides an ideal configuration for dopamine modulation
      of glutamatergic transmission. In this issue of Neuron, Bamford et al. report
      that dopamine inhibits glutamate release in a selective manner by activating
      presynaptic D2 receptors.

PMID- 15157415
TI  - The potion's magic.
AB  - During remembering, a perception of the past is constructed that includes sensory
      details of the original episode. In this issue of Neuron, Gottfried and
      colleagues provide evidence for selective piriform activation during recognition
      of visual cues previously paired with scents. These data provide evidence of
      sensory-specific reactivation of olfactory cortex during remembering.

PMID- 15157416
TI  - p75NTR is positively promiscuous: novel partners and new insights.
AB  - Although identified almost 20 years ago, the precise physiological role of the
      p75 neurotrophin receptor (p75NTR) has remained elusive. Recent studies have
      revealed that p75NTR is a component of three distinct receptor platforms that
      bind different ligands and that, under differing circumstances, facilitate cell
      survival, cell death, or growth inhibition. These recent developments provide new
      insights into the functions of this enigmatic receptor.

PMID- 15157417
TI  - Excitation-neurogenesis coupling in adult neural stem/progenitor cells.
AB  - A wide variety of in vivo manipulations influence neurogenesis in the adult
      hippocampus. It is not known, however, if adult neural stem/progenitor cells
      (NPCs) can intrinsically sense excitatory neural activity and thereby implement a
      direct coupling between excitation and neurogenesis. Moreover, the theoretical
      significance of activity-dependent neurogenesis in hippocampal-type memory
      processing networks has not been explored. Here we demonstrate that excitatory
      stimuli act directly on adult hippocampal NPCs to favor neuron production. The
      excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors
      on the proliferating precursors. Excitation through this pathway acts to inhibit
      expression of the glial fate genes Hes1 and Id2 and increase expression of
      NeuroD, a positive regulator of neuronal differentiation. These activity-sensing
      properties of the adult NPCs, when applied as an "excitation-neurogenesis
      coupling rule" within a Hebbian neural network, predict significant advantages
      for both the temporary storage and the clearance of memories.

PMID- 15157418
TI  - Spontaneous neural activity is required for the establishment and maintenance of
      the olfactory sensory map.
AB  - We have developed a genetic approach to examine the role of spontaneous activity
      and synaptic release in the establishment and maintenance of an olfactory sensory
      map. Conditional expression of tetanus toxin light chain, a molecule that
      inhibits synaptic release, does not perturb targeting during development, but
      neurons that express this molecule in a competitive environment fail to maintain
      appropriate synaptic connections and disappear. Overexpression of the inward
      rectifying potassium channel, Kir2.1, diminishes the excitability of sensory
      neurons and more severely disrupts the formation of an olfactory map. These
      studies suggest that spontaneous neural activity is required for the
      establishment and maintenance of the precise connectivity inherent in an
      olfactory sensory map.

PMID- 15157419
TI  - New synaptic bouton formation is disrupted by misregulation of microtubule
      stability in aPKC mutants.
AB  - The Baz/Par-3-Par-6-aPKC complex is an evolutionarily conserved cassette critical
      for the development of polarity in epithelial cells, neuroblasts, and oocytes.
      aPKC is also implicated in long-term synaptic plasticity in mammals and the
      persistence of memory in flies, suggesting a synaptic function for this cassette.
      Here we show that at Drosophila glutamatergic synapses, aPKC controls the
      formation and structure of synapses by regulating microtubule (MT) dynamics. At
      the presynapse, aPKC regulates the stability of MTs by promoting the association
      of the MAP1Brelated protein Futsch to MTs. At the postsynapse, aPKC regulates the
      synaptic cytoskeleton by controlling the extent of Actin-rich and MT-rich areas.
      In addition, we show that Baz and Par-6 are also expressed at synapses and that
      their synaptic localization depends on aPKC activity. Our findings establish a
      novel role for this complex during synapse development and provide a cellular
      context for understanding the role of aPKC in synaptic plasticity and memory.

PMID- 15157420
TI  - G protein-coupled receptor kinase function is essential for chemosensation in C.
      elegans.
AB  - G protein-coupled receptors (GPCRs) mediate diverse signaling processes,
      including olfaction. G protein-coupled receptor kinases (GRKs) are important
      regulators of G protein signal transduction that specifically phosphorylate
      activated GPCRs to terminate signaling. Despite previously described roles for
      GRKs in GPCR signal downregulation, animals lacking C. elegans G protein-coupled
      receptor kinase-2 (Ce-grk-2) function are not hypersensitive to odorants.
      Instead, decreased Ce-grk-2 function in adult sensory neurons profoundly disrupts
      chemosensation, based on both behavioral analysis and Ca(2+) imaging. Although
      mammalian arrestin proteins cooperate with GRKs in receptor desensitization, loss
      of C. elegans arrestin-1 (arr-1) does not disrupt chemosensation. Either
      overexpression of the C. elegans Galpha subunit odr-3 or loss of eat-16, which
      encodes a regulator of G protein signaling (RGS) protein, restores chemosensation
      in Ce-grk-2 mutants. These results demonstrate that loss of GRK function can lead
      to reduced GPCR signal transduction and suggest an important role for RGS
      proteins in the regulation of chemosensation.

PMID- 15157421
TI  - A highly Ca2+-sensitive pool of vesicles contributes to linearity at the rod
      photoreceptor ribbon synapse.
AB  - Studies of the properties of synaptic transmission have been carried out at only
      a few synapses. We analyzed exocytosis from rod photoreceptors with a combination
      of physiological and ultrastructural techniques. As at other ribbon synapses, we
      found that rods exhibited rapid kinetics of release, and the number of vesicles
      in the releasable pool is comparable to the number of vesicles tethered at ribbon
      style active zones. However, unlike other previously studied neurons, we
      identified a highly Ca(2+)-sensitive pool of releasable vesicles with a
      relatively shallow relationship between the rate of exocytosis and [Ca(2+)](i)
      that is nearly linear over a presumed physiological range of intraterminal
      [Ca(2+)]. The low-order [Ca(2+)] dependence of release promotes a linear
      relationship between Ca(2+) entry and exocytosis that permits rods to relay
      information about small changes in illumination with high fidelity at the first
      synapse in vision.

PMID- 15157422
TI  - Postfusional control of quantal current shape.
AB  - Whether glutamate is released rapidly, in an all-or-none manner, or more slowly,
      in a regulated manner, is a matter of debate. We analyzed the time course of
      excitatory postsynaptic currents (EPSCs) at glutamatergic neuromuscular junctions
      of Drosophila and found that the decay phase of EPSCs was protracted to a
      variable extent. The protraction was more pronounced in evoked and spontaneous
      quantal EPSCs than in action potential-evoked multiquantal EPSCs; reduced in
      quantal EPSCs from endophilin null mutants, which maintain release via kiss-and
      run; and dependent on synaptotagmin isoform, calcium, and protein
      phosphorylation. Our data indicate that glutamate is released from individual
      synaptic vesicles for milliseconds through a fusion pore. Quantal glutamate
      discharge time course depends on presynaptic calcium inflow and the molecular
      composition of the release machinery.

PMID- 15157423
TI  - Cataplexy-active neurons in the hypothalamus: implications for the role of
      histamine in sleep and waking behavior.
AB  - Noradrenergic, serotonergic, and histaminergic neurons are continuously active
      during waking, reduce discharge during NREM sleep, and cease discharge during REM
      sleep. Cataplexy, a symptom associated with narcolepsy, is a waking state in
      which muscle tone is lost, as it is in REM sleep, while environmental awareness
      continues, as in alert waking. In prior work, we reported that, during cataplexy,
      noradrenergic neurons cease discharge, and serotonergic neurons greatly reduce
      activity. We now report that, in contrast to these other monoaminergic "REM-off"
      cell groups, histamine neurons are active in cataplexy at a level similar to or
      greater than that in quiet waking. We hypothesize that the activity of histamine
      cells is linked to the maintenance of waking, in contrast to activity in
      noradrenergic and serotonergic neurons, which is more tightly coupled to the
      maintenance of muscle tone in waking and its loss in REM sleep and cataplexy.

PMID- 15157424
TI  - Physiological properties of hypothalamic MCH neurons identified with selective
      expression of reporter gene after recombinant virus infection.
AB  - Neurons that synthesize melanin-concentrating hormone (MCH) may modulate arousal
      and energy homeostasis. The scattered MCH neurons have been difficult to study,
      as they have no defining morphological characteristics. We have developed a viral
      approach with AAV for selective long-term reporter gene (GFP) expression in MCH
      neurons, allowing the study of their cellular physiology in hypothalamic slices.
      MCH neurons showed distinct membrane properties compared to other neurons
      infected with the same virus with a cytomegalovirus promoter. Transmitters of
      extrahypothalamic arousal systems, including norepinephrine, serotonin, and the
      acetylcholine agonist muscarine, evoked direct inhibitory actions. Orexigenic
      neuropeptide Y was inhibitory by pre- and postsynaptic mechanisms; an
      anorexigenic melanocortin agonist had no effect. In contrast, the hypothalamic
      arousal peptide hypocretin/orexin evoked a direct inward current and increased
      excitatory synaptic activity and spike frequency in the normally silent MCH
      neurons. Together, these data support the view that MCH neurons may integrate
      information within the arousal system in favor of energy conservation.

PMID- 15157425
TI  - Heterosynaptic dopamine neurotransmission selects sets of corticostriatal
      terminals.
AB  - Dopamine input to the striatum is required for voluntary motor movement,
      behavioral reinforcement, and responses to drugs of abuse. It is speculated that
      these functions are dependent on either excitatory or inhibitory modulation of
      corticostriatal synapses onto medium spiny neurons (MSNs). While dopamine
      modulates MSN excitability, a direct presynaptic effect on the corticostriatal
      input has not been clearly demonstrated. We combined optical monitoring of
      synaptic vesicle exocytosis from motor area corticostriatal afferents and
      electrochemical recordings of striatal dopamine release to directly measure
      effects of dopamine at the level of individual presynaptic terminals. Dopamine
      released by either electrical stimulation or amphetamine acted via D2 receptors
      to inhibit the activity of subsets of corticostriatal terminals. Optical and
      electrophysiological data suggest that heterosynaptic inhibition was enhanced by
      higher frequency stimulation and was selective for the least active terminals.
      Thus, dopamine, by filtering less active inputs, appears to reinforce specific
      sets of corticostriatal synaptic connections.

PMID- 15157426
TI  - Early amygdala reaction to fear spreading in occipital, temporal, and frontal
      cortex: a depth electrode ERP study in human.
AB  - The amygdala involvement in fear processing has been reported in behavioral,
      electrophysiological, and functional imaging studies. However, the literature
      does not provide precise data on the temporal course of facial emotional
      processing. Intracranial event-related potentials to facial expressions were
      recorded in epileptic patients implanted with depth electrodes during a
      presurgical evaluation. Specific potentials to fear beginning 200 ms poststimulus
      were observed in amygdala, both individually in two patients and in a ten patient
      population study. These potentials occurred 100 ms earlier than potentials to
      disgust recorded in insula in a previous study. Potentials to fear were confined
      in amygdala during a first transient period and then, during a second period of
      sustained activity, spread to occipito-temporal, anterior temporal, and
      orbitofrontal cortex in two patients. This study clarifies the temporal course of
      the involvement of these structures known to be part of a neural network
      recruited to process emotional information.

PMID- 15157427
TI  - Multiple spotlights of attentional selection in human visual cortex.
AB  - Spatially directed attention strongly enhances visual perceptual processing. The
      metaphor of the "spotlight" has long been used to describe spatial attention;
      however, there has been considerable debate as to whether spatial attention must
      be unitary or may be split between discrete regions of space. This question was
      addressed here through functional MR imaging of human subjects as they performed
      a task that required simultaneous attention to two briefly displayed and masked
      targets at locations separated by distractor stimuli. These data reveal
      retinotopically specific enhanced activation in striate and extrastriate visual
      cortical representations of the two attended stimuli and no enhancement at the
      intervening representation of distractor stimuli. This finding of two spotlights
      was obtained within a single cortical hemisphere and across the two hemispheres.
      This provides direct evidence that spatial attention can select, in parallel,
      multiple low-level perceptual representations.

PMID- 15157429
TI  - Secretory lysosomes - a special mechanism of regulated secretion in haemopoietic
      cells.
AB  - The secretory granules o f cells derived from the haemopoietic lineage are
      'secretory lysosomes' containing both lysosomal hydrolases and secretory
      proteins. Studies on cytotoxic T lymphocytes (CTLs) have elucidated several of
      the mechanisms that regulate protein sorting to, and secretion from, this unusual
      secretory organelle. In particular, recent findings from a CTL mutant have led to
      the hypothesis that CTLs, and other cells of the haemopoietic lineage, use
      specialized sorting and secretory mechanisms in which the lysosome functions as a
      regulated secretory granule.

PMID- 15157428
TI  - Remembrance of odors past: human olfactory cortex in cross-modal recognition
      memory.
AB  - Episodic memory is often imbued with multisensory richness, such that the recall
      of an event can be endowed with the sights, sounds, and smells of its prior
      occurrence. While hippocampus and related medial temporal structures are
      implicated in episodic memory retrieval, the participation of sensory-specific
      cortex in representing the qualities of an episode is less well established. We
      combined functional magnetic resonance imaging (fMRI) with a cross-modal
      paradigm, where objects were presented with odors during memory encoding. We then
      examined the effect of odor context on neural responses at retrieval when these
      same objects were presented alone. Primary olfactory (piriform) cortex, as well
      as anterior hippocampus, was activated during the successful retrieval of old
      (compared to new) objects. Our findings indicate that sensory features of the
      original engram are preserved in unimodal olfactory cortex. We suggest that
      reactivation of memory traces distributed across modality-specific brain areas
      underpins the sensory qualities of episodic memories.

PMID- 15157430
TI  - JAKs and STATs branch out.
AB  - The JAK-STAT signal-transduction pathway is utilized by a wide range of cytokines
      to regulate gene expression. Cytokines activate members of the JAK family o f
      protein tyrosine kinases, which in turn activate, by tyrosine phosphorylation,
      one or more STAT transcription factor family members. Activated STATs form
      dimers, translocate to the nucleus and bind to response elements to induce
      transcription. Recent findings are beginning to connect JAKs and STATs with other
      signalling pathways: JAKs may phosphorylate and activate signalling proteins
      other than STATs, and STATs can be phosphorylated by non-]AK tyrosine kinases.
      STAT activity can also be modulated by serine phosphorylation.

PMID- 15157431
TI  - 14-3-3 and its possible role in co-ordinating multiple signalling pathways.
AB  - Members of the 14-3-3 family are homo- and the heterodimeric proteins mediating
      interaction between diverse components of many biological activities. The role of
      these proteins has been unclear for some time, but they are now gaining
      acceptance as a novel type of chaperone protein that modulates interactions
      between components of signal-transduction pathways. It is becoming apparent from
      recent studies that phosphorylation of the binding partner and possibly also the
      14-3-3 proteins themselves is important in regulating these interactions.
      Analysis of the major sites of phosphorylation in Raf has led to the
      identification of a novel sequence motif, R(S)X(1,2)S(P)X(P), that may represent
      a conserved interaction site for 14-3-3-binding proteins.

PMID- 15157432
TI  - Structure and function of the centriole in animal cells: progress and questions.
AB  - The centriole is a well-recognized, yet poorly understood, organelle present in
      many eukaryotic cells. Despite excellent electron-microscopic descriptions of its
      basic triplet microtubule structure, almost nothing is known of its specific
      molecular components. Here, Bodo Lange and Keith Gull survey centriole structure,
      duplication and maturation within the cell cycle and focus attention on the
      possible roles and function of centrioles as components of the centrosome in
      animal cells.

PMID- 15157433
TI  - Getting it together in plant virus movement: cooperative interactions between
      bipartite geminivirus movement proteins.
AB  - To move cell-to-cell and systemically infect the host, plant viruses must cross
      the barrier posed by the plant cell wall. Plant viruses accomplish this through
      strategies that alter the architecture of the infected cell, eliminating this
      barrier through the action of viral-encoded 'movement proteins'. Detailed studies
      of a number of cytoplasmically replicating viruses suggest that movement proteins
      interact with components of the cytoskeleton and transport systems of the plant
      cell to allow passage of progeny into adjacent cells. Recent work on the two
      movement proteins encoded by the phloem-restricted geminivirus squash leaf curl
      virus has defined unique aspects of nuclear transport and protein protein
      interaction in the movement of this nuclear-replicating virus, and suggests that
      post-translational phosphorylation may be important in the regulation of movement
      protein function.

PMID- 15157434
TI  - Virtual conferences.
AB  - An interview with Barry Hardy, conducted in May and June 1996 by e-mail and on 12
      June 1996 at a MOO site. The development of the Internet has provided the
      opportunity o f conducting meetings and conferences electronically. In this
      interview, Barry Hardy outlines the main principles involved in staging and
      attending a 'virtual meeting', and issues an invitation to the readers o f trends
      in CELL BIOLOGY to become involved in organizing the first international
      electronic cell-biology conference.

PMID- 15157435
TI  - Wnt signal transduction: more than one wat to skin a (beta-)cat?
AB  - Genetic and biochemical studies have suggested that signal transduction by the
      Wnt pathway is very different to the familiar protein-kinase cascade of the Ras
      pathway. Among the more intriguing findings is that beta-catenin, a component of
      intercellular adhesive junctions, is a central component in the Wnt signalling
      pathway. Recent studies suggest ways in which beta-catenin might serve as a focal
      point for regulation of adhesion, gene expression and cell proliferation.

PMID- 15157436
TI  - Signal-mediated nuclear export pathways of proteins and RNAs.
AB  - Although it has been known for several years that most nuclear-encoded RNAs and
      some patients can be exported from the nucleus to the cytoplasm, the molecular
      mechanisms of these transport processes have been poorly understood. Recently,
      signals that can induce the rapid and active nuclear export of macromolecules
      have been identified in the HIV-1 Rev protein, the inhibitor of cAMP-dependent
      protein kinase (PKI) and the hnRNP A1 protein. Thus, nuclear export appears to be
      mechanistically similar to nuclear import that it requires specific signal
      receptor systems.

PMID- 15157437
TI  - Getting to the heart of beta-tubulin.

PMID- 15157438
TI  - Rho: a connection between membrane receptor signalling and the cytoskeleton.
AB  - The Rho family of GTP-binding proteins has yielded fresh insights into cell
      signalling in relation to motility, shape and the control of the actin
      cytoskeleton. Rho itself is probably near the top of several diverse signalling
      cascades and has been implicated in cell adhesion, actin filament organization,
      control of mitogen-activated protein kinase pathways and phospholipid synthesis
      and turnover. As a member of the Ras superfamily, Rho is regulated by GDP-GTP
      exchange factors (GEFs) that have homology to the dbl oncogene, and by GTPase
      activating proteins (GAPs). These proteins regulate the nucleotide (GDP or GTP)
      bound to Rho, thus determining the activity of Rho and the interactions of Rho
      with many of its downstream targets. In the past year, many new targets of Rho
      have been identified, which hopefully will uncover molecular connections among
      the diverse downstream effects of Rho activation.

PMID- 15157439
TI  - Crosstalk between cell adhesion molecules: vinculin as a paradigm for regulation
      by conformation.
AB  - With the identification of ever more protein components associated with cellular
      adhesion sites, the nature of the mechanisms underlying assembly and maintenance
      of these important cellular structures was in danger of becoming completely
      intangible. However, new information on how the interaction between the different
      proteins can be regulated is beginning to shed more light on this problem. In
      particular, recent biochemical and electron microscopic data on the overall
      structure and function of vinculin, one of the key structural proteins involved
      in cellular adhesion, leads to a novel model for the regulation of cellular
      adhesion.

PMID- 15157440
TI  - Principles of selective transport: coat complexes hold the key.
AB  - The transport of protein through the secretory pathway of eukaryotic cells relies
      on small vesicular carriers, which mediate the movement of cargo between
      different compartments. Here, Meir Aridor and Bill Balch summarize what is
      currently known about the role of the cytosolic coat complexes in directing the
      formation and selective composition of vesicular carriers, and propose that a
      selective-transport model should now form the basis for study of membrane traffic
      in the secretory pathway.

PMID- 15157441
TI  - Probing the mobility of membrane proteins inside the cell.
AB  - Studies using a variety of microscopy-based approaches have led to a consensus
      that most cell-surface proteins are highly mobile and diffuse rapidly within
      fenced microdomains. Little attention, however, has so far been given to the
      analysis of the mobility of intracellular membrane proteins because of their
      comparative inaccessibility. Recent advances in microinjection, confocal
      microscopy and the construction of epitope-tagged proteins or of hybrids with an
      intrinsically fluorescent protein have allowed intracellular membrane proteins to
      be studied using approaches previously applied to characterize the mobility of
      cell-surface proteins. Confocal fluorescence recovery after photobleaching (c
      FRAP) experiments show that intracellular membrane proteins may also be highly
      mobile.

PMID- 15157442
TI  - Meeting of cell-cell adhesion, communication and signalling at the junction.

PMID- 15157443
TI  - ICE/CED-3 proteasesin apoptosis.
AB  - An expanding family of cysteine proteases, of which interleukin-1beta-converting
      enzyme (ICE) is the prototype, has been shown to play a key role in mammalian
      cell apoptosis. ICE is both a structural and functional homologue of the nematode
      'death gene' ced-3. Here, Moira Whyte discusses how functional characterization
      of these ICE-like proteases and identification of their substrates is helping to
      elucidate the biochemical processes underlying the stereotyped morphology of
      apoptosis and to identify potential targets for therapy.

PMID- 15157444
TI  - Centrosomes and microtubules: wedded with a ring.
AB  - How centrosomes nucleate microtubule growth is a question that has puzzled cell
      biologists for decades. It has been suspected for some time that a centrosome
      contains multiple copies of a basic microtubule-nucleating structure, each of
      which is responsible for nucleating a single microtubule. This suspicion has now
      been confirmed. A ring of gamma-tubulin molecules, associated with a large
      protein complex, apparently serves as the long-sought-after microtubule
      nucleating structure.

PMID- 15157445
TI  - Cell-cell transfer of GPI-linked molecules.

PMID- 15157448
TI  - Cell_adhesion@ exciting.important. edu/com.

PMID- 15157449
TI  - Solid-state protein networks?

PMID- 15157450
TI  - Antigen presentation: immunologists co-opt cell biology.

PMID- 15157451
TI  - Competition is not our enemy.

PMID- 15157452
TI  - Phospholipids: synthesis, sorting, subcellular traffic - the yeast approach.
AB  - Most of the enzymes and genes required for lipid biosynthesis and degradation in
      the budding yeast Saccharomyces cerevisiae have now been identified and the
      global mechanisms that regulate their activity are being established. Synthesis
      of phospholipids is restricted to specific subcellular compartments, and the
      lipids migrate from their site of formation to their final destination. In
      addition to synthesis, remodelling and degradation of phospholipids controls the
      content of the lipid portion of cellular membranes, while highly specific
      phospholipases catalyse the release of lipid-based second messengers. In this
      review, we describe the current understanding of the organization and regulation
      of phospholipid metabolism in yeast, and discuss the mechanisms that have been
      proposed for intracellular lipid transport.

PMID- 15157453
TI  - Peptide presentation by MHC class I molecules.
AB  - The presentation of peptides by class I histocompatibility molecules plays a
      central role in the cellular immune response to virally infected or transformed
      cells. The main steps in this process include the degradation of both self and
      'foreign' proteins to short peptides in the cytosol, translocation of peptides
      into the lumen of the endoplasmic reticulum, binding of a subset of peptides to
      assembling class I molecules and expression of class-I-peptide complexes at the
      cell surface for examination by cytotoxic T cells. A molecular understanding of
      most of these steps is emerging, revealing a remarkable coordination between the
      processes of peptide translocation, delivery and binding to class I molecules.

PMID- 15157455
TI  - Modelling tissues on the computer.

PMID- 15157454
TI  - GSK3: a SHAGGY frog story.
AB  - Glycogen synthase kinase 3 was discovered in mammals several years ago but only
      recently has it become clear that this enzyme is acutely regulated by hormones
      such as insulin and by growth factors. In mammals, it appears to be controlled by
      a signalling pathway linked to phosphoinositide 3-kinase and may regulate a range
      of biosynthetic processes. Evidence is now accumulating that GSK3 plays a key
      role in the regulation of cell fate and differentiation in many eukaryotic
      species.

PMID- 15157456
TI  - The role of intracellular cholesterol transport in cholesterol homeostasis.
AB  - How cholesterol is transported among the membranes of the cell is obscure.
      Similarly, the mechanisms governing the abundance of cell cholesterol are not
      entirely understood. It may be, however, that a link exists between the
      intracellular transport of cholesterol and its homeostasis. We propose that
      cholesterol circulates between the plasma membrane, which contains the bulk of
      the sterol, and organelle membranes, which contain only traces. A putative sensor
      translates small fluctuations in plasma membrane cholesterol into relatively
      large changes in this flux, thereby setting the magnitude of the intracellular
      pools. The cholesterol concentration in the endoplasmic reticulum and
      mitochondrial membranes then governs the activities of proteins embedded therein
      that mediate cholesterol transformations. This arrangement creates a feedback
      loop through which the intracellular effectors regulate the abundance of plasma
      membrane cholesterol.

PMID- 15157457
TI  - Actin' like actin?
AB  - The most biologically significant property of actin is its ability to self
      associate and form two-stranded polymeric microfilaments. In living cells, these
      micro filaments form the actin cytoskeleton, essential for maintenance of the
      shape, passive mechanical properties and active motility of eukaryotic cells.
      Recently discovered actin-related proteins (ARPs) appear to share a common
      ancestor with conventional actin. At present, six classes of ARPs have been
      discovered, three of which have representatives in diverse species across
      eukaryotic phyla and may share functional characteristics with conventional
      actin. The three most ubiquitous ARPs are predicted to share a common core
      structure with actin and contain all the residues required for ATP binding.
      Surface residues involved in protein protein interactions, however, have
      diverged. Models of these proteins based on the atomic structure of actin provide
      some clues about how ARPs interact with each other, with conventional actin and
      with conventional actin-binding proteins.

PMID- 15157458
TI  - Actin-related protein 1 and cytoplasmic dynein-based motility - what's the
      connection?
AB  - The actin-related protein Arp1 works in conjunction with the microtubule-based
      motor cytoplasmic dynein to drive many types of intracellular motility. In
      vertebrate cells, Arp1 is present exclusively in the form of a 37-nm filament
      that constitutes the backbone of dynactin, a 1.2-MDa macromolecular complex
      containing nine other polypeptides. Dynactin has been proposed to function as the
      link between dynein and its cargo. Recent work indicates that the dynactin
      subunit p150(Glued) mediates the interaction of the dynactin molecule with dynein
      and microtubules, leaving the Arp1 filament as a possible cargo-binding domain.
      Mechanisms for binding of F-actin to membranes are discussed as models of the
      Arp1-membrane interaction.

PMID- 15157459
TI  - Fumonisins: fungal toxins that shed light on sphingolipid function.
AB  - Fumonisins are sphinganine analogues produced by Fusarium moniliforme and related
      fungi. They inhibit ceramide synthase and block the biosynthesis o f complex
      sphingolipids, promoting accumulation o f sphinganine and sphinganine 1
      phosphate. Disruption o f sphingolipid metabolism by fumonisin B(1) alters cell
      cell interactions, the behaviour o f cell-surface proteins, the activity o f
      protein kinases, the metabolism of other lipids, and cell growth and viability.
      This multitude of effects probably accounts for the toxicity and carcinogenicity
      of these mycotoxins. Naturally occurring inhibitors o f sphingolipid metabolism
      such as fumonisins are proving to be powerful tools for studying the diverse
      roles of sphingolipids in cell regulation and disease.

PMID- 15157460
TI  - Pumping iron in the '90s.
AB  - The role o f iron in cell division, cell death and human disease has recently
      gained increased attention. The best studied process for iron uptake into
      mammalian cells involves traps ferrin and its receptor. This review discusses
      evidence supporting the existence of other routes by which iron can enter
      mammalian cells. Specifically, iron uptake by the cell-surface GPI-linked traps
      ferrin homologue, melanotransferrin or p97, is described and possible functions
      of this traps ferrin-independent pathway are proposed.

PMID- 15157461
TI  - The spindle-assembly checkpoint: aiming for a perfect mitosis, every time.
AB  - Checkpoints reduce the frequency of errors in cell division by delaying the
      progress of the cell cycle until certain processes are complete. The spindle
      assembly checkpoint prevents the onset of anaphase until a bipolar spindle is
      present and all chromosomes are attached to the spindle. Evidence from yeast and
      mammalian cells suggests that kinetochores are at least one source of the signal
      that stops the cell cycle. Recent studies in budding yeast have begun to define
      the signal-transduction pathway involved in the spindle-assembly checkpoint, but
      details of the endpoint of the pathway, where these signals interact with the
      cell-cycle machinery, remain to be characterized.

PMID- 15157462
TI  - Mapping the three-dimensional organization of microtubules in mitotic spindles of
      yeast.

PMID- 15157463
TI  - Fusion and confusion in the secretory pathway.

PMID- 15157464
TI  - Transfer of exogenous glycosylphos-phatidylinositol (GPI)-linked molecules to
      plasma membranes.
AB  - Purified GPI-linked molecules incorporate spontaneously in vitro into mammalian
      cell plasma membranes. Recent evidence suggests that the transferred molecules
      insert stably into the external leaflet of the acceptor cell plasma membrane
      through their acyl chains and behave subsequently in a way similar to endogenous
      GPI-linked molecules. Transfer of GPI-linked proteins between cells has also been
      documented in vivo and may explain the uptake by host cells o f pathogen-derived
      virulence factors carrying a GPI anchor. In this comment article, Subburaj
      Ilangumaran, Peter Robinson and Daniel Hoessli review what is known about GPI
      transfer and discuss the use of GPI transfer for transient cell-surface
      expression of foreign proteins.

PMID- 15157465
TI  - pH, EF-1alpha and the cytoskeleton.
AB  - One of the unexpected cellular components found interacting with the cytoskeleton
      is elongation factor 1 alpha (EF-1alpha). How this interaction is regulated is
      not clear, but pH may be a potent regulator. Interestingly, pH also regulates the
      amount of protein translation occurring in many cell systems. In this paper, the
      authors suggest that sequestration of EF-1alpha in the cytoskeleton may play a
      key role in regulating the spatial distribution of macromolecular assembly in a
      way that is dependent on cytoplasmic pH.

PMID- 15157466
TI  - Membrane tension.

PMID- 15157468
TI  - Vaults are the answer, what is the question?
AB  - Vaults are large cytoplasmic ribonucleoprotein (RNP) particles of eukaryotic
      cells, whose considerable abundance and striking evolutionary conservation argue
      for an important general cellular function. Early studies on vaults focused on
      the structural features and cellular distribution of the particle and will only
      be summarized briefly here. In this article, we discuss the molecular
      characterization of vault components and describe genetic studies carried out in
      Dictyostelium. The recent finding that the major vault protein is elevated in non
      P-glycoprotein multidrug resistant cancer cells has direct implications
      concerning the function of the vault particle and indicates a potential role for
      vaults in resistance of tumour cells to anticancer drugs.

PMID- 15157469
TI  - CLIPs for organelle-microtubule interactions.
AB  - Interactions of intracellular membranes with microtubules play a fundamental role
      in the dynamic organization of cytoplasmic organelles. The microtubule-based
      motors kinesin and cytoplasmic dynein are responsible for directed movement of
      vesicles and organelles, but in vitro assays indicate the existence of another
      class of proteins linking membranes to microtubules. CLIP-170, a cytoplasmic
      linker protein that mediates binding of endosomes to microtubules, provides a
      paradigm for understanding how these proteins may complement the role of motors
      in regulating microtubule-dependent membrane trafficking.

PMID- 15157470
TI  - Mechanisms restricting DNA replication to once per cell cycle: MCMS, pre
      replicative complexes and kinases.
AB  - An important aspect of cell behaviour is that DNA replication happens only once
      per cell cycle. Replicated DNA is unable to re-replicate until cell division has
      occurred. Unreplicated DNA is in a replication-competent or 'licensed' state. The
      ability to replicate is lost in S phase and regained following passage through
      mitosis. Recent evidence has implicated an MCM (minichromosome maintenance)
      protein complex and the Cdc6 protein in determining replication competence.
      Regeneration of replication competence upon passage through mitosis entails
      changes in protein kinase activity, of which the MCMs are a likely target.
      Features of the mechanism that restricts DNA replication to once per cell cycle
      appear to be conserved throughout eukaryotes.

PMID- 15157471
TI  - Nuclear targeting of SV40 and adenovirus.
AB  - Import o f viral DNA into the nucleus is essential for the successful replication
      o f DNA tumour viruses. To achieve this goal, viruses have adapted strategies to
      traverse the barriers between the plasma membrane and the nucleus o f a host
      cell. Two DNA tumour viruses, simian virus 40 and adenovirus, achieve the nuclear
      entry step in slightly different ways. SV40 DNA enters the nucleus through the
      nuclear pore complexes (NPCs) in apparently intact virions. By contrast,
      adenovirus particles dissociate near the NPC before the viral DNA is imported
      into the nucleus. In both cases, karyophilic protein components o f the viruses
      appear to mediate nuclear entry o f the viral genomes. In this article, we
      discuss how an understanding o f the cell biology o f virus entry can help us
      understand the process o f nuclear transport.

PMID- 15157472
TI  - The yeast two-hybrid system: prospects for protein linkage maps.

PMID- 15157473
TI  - The beaded filament of the eye lens: an unexpected key to intermediate filament
      structure and function.
AB  - In 1959, an unusual filamentous polymer, now called the beaded filament, was
      described in the lens of the eye. The constituent proteins, assembly properties
      and functions of the beaded filament have been elusive. The recent publication of
      the sequences for two major lens filament proteins (CP49 and filensin) and the
      reconstitution in vitro of structures closely resembling beaded filaments,
      suggests that the beaded filament is related structurally to intermediate
      filaments (IFs). The association of the lenticular chaperones, the alpha
      crystallins, with the filament contributes to the characteristic beaded
      morphology, as well as giving important clues to the function of this unusual
      filament in the lens. These recent results have several implications for IF
      function and assembly.

PMID- 15157474
TI  - In search of membrane receptors for microtubule-based motors - is kinectin a
      kinesin receptor?
AB  - The past few years have seen an explosion in the number of molecular motors
      reported in the literature. By us the energy of hydrolysis, these motors move
      various organelles along cytoskeletal 'tracks' within the cell. It is thought
      that some of the specificity of movement resides in receptors on the surface of
      the cargo organelles, but, in general, little is known about these molecules. In
      this article, Janis Burkhardt discusses the evidence that the protein kinectin
      serves as a membrane receptor for kinesin, and describes how motor-receptor
      proteins may interact with other components of the motility machinery to generate
      regulated movement of membrane organelles.

PMID- 15157475
TI  - Are there similarities between the polarization of the C. elegans embryo and of
      an epithelial cell?

PMID- 15157476
TI  - Organelle transport along microtubules - the role of KIFs.
AB  - Organelle transporters are very important for cellular morphogenesis and other
      cellular functions, conveying and targeting important materials to the correct
      destination, often at considerable velocities. One of the first proteins to be
      identified as a motor was kinesin, and recently at least 10 new kinesin
      superfamily proteins (KIFs) have been described. Characterization of some of them
      reveals that each member can convey a specific organelle or cargo, although there
      is some redundancy. It has also become clear that there are distinct subclasses
      of KIFs that form monomeric, heterodimeric and homodimeric motors. Here, Nobutaka
      Hirokawa reviews what is known about the kinesin superfamily and discusses how a
      study of the different types of motors is helping to elucidate the mechanism of
      mechanical force generation.

PMID- 15157477
TI  - Snapshots of membrane-translocating proteins.
AB  - To learn about the molecular mechanism of protein translocation across the
      membrane of the endoplasmic reticulum (ER), the environment of nascent chains
      during the translocation process has been characterized using a variety of
      crosslinking approaches. These techniques have led to the identification of
      several proteins that interact transiently with the newly synthesized protein in
      the cytosol, during its passage across the membrane of the ER and in the ER
      lumen. Furthermore, lipids have been found to be in contact with membrane
      inserted nascent chains, suggesting that the polypeptide enters the membrane in a
      protein-lipid interface.

PMID- 15157478
TI  - Dissecting desaturation: plants prove advantageous.
AB  - Fatty acid desaturases play important roles in controlling the physical
      properties o f membranes and in the synthesis of signal molecules such as
      prostaglandins and pheromones. Most desaturases are membrane proteins that have
      been recalcitrant to characterization by conventional biochemical methods. Only
      one enzyme o f this class has been characterized from animals or fungi. In this
      context, plants have proved to be useful sources of experimental materials.
      Substantial progress has been made in characterizing and manipulating nine
      classes of desaturases that control the fatty acid composition o f both plant
      membranes and plant storage lipids, which account for approximately -30% of the
      calories in the human diet.

PMID- 15157479
TI  - Use of photocrosslinkers in cell biology.

PMID- 15157480
TI  - Communicate your science! ... Writing research reports.

PMID- 15157481
TI  - Learning on the web.

PMID- 15157482
TI  - The search for the primary function of the Ran GTPase continues.
AB  - It has been nearly 20 years since the discovery of the first component of the Ran
      GTPase pathway. Since then, nearly 100 articles, more than half of which have
      been published in the past three years, have reported the identification of
      additional components of the system and the existence of their structural and
      functional homologues in organisms ranging from yeast to man. The Ran system
      affects a vast array of nuclear processes including RNA metabolism, DNA
      replication, chromosome condensation and decondensation, and nucleocytoplasmic
      transport of protein and RNA. The current challenge is to identify the molecular
      targets that link the Ran-GTPase system to this collection o f nuclear processes.

PMID- 15157483
TI  - Modulation of membrane dynamics and cell motility by membrane tension.
AB  - The plasma membrane of most cells is drawn tightly over the cytoskeleton of the
      cell, resulting in a significant tension being developed in the membrane. The
      tension in the membrane can be calculated from the force required to separate it
      from the cytoskeleton; and the force itself can be measured rapidly by using
      laser tweezers. Recent observations indicate that decreasing membrane tension
      stimulates endocytosis and increasing tension stimulates secretion. Thus,
      membrane tension provides a simple physical mechanism to control the area of the
      plasma membrane. Here, we speculate that tension is a global parameter that the
      cell uses to control physically plasma membrane dynamics, cell shape and cell
      motility.

PMID- 15157484
TI  - Phosphoinositide 3-kinases and membrane traffic.
AB  - Phosphoinositide 3-kinases (PI 3-kinases) and their 3-phosphoinositide products
      were identified initially as components of intracellular signalling pathways
      emanating from cell surface receptors. A new role for 3-phosphoinositides in the
      constitutive movement o f proteins from one intracellular compartment to another
      was proposed with the discovery of homology between the product of a yeast gene
      important for vacuolar sorting, Vps34p, and a mammalian PI 3-kinase. Recent
      studies have implicated PI 3-kinase as an essential component in membrane traffic
      at specific steps o f the trans-Golgi-network-endosomal pre-lysosomal system.
      Evidence largely emerging from the insulin-stimulated glucose transport system
      suggests that PI 3-kinase may also mediate the effects o f growth factors on
      membrane traffic events. These studies suggest a possible link between growth
      factor-stimulated and constitutive membrane traffic in the endosomal system.

PMID- 15157485
TI  - Topology of glycosphingolipid degradation.
AB  - Glycosphingolipids (GSLs) form cell-type-specific patterns on the surface of
      eukaryotic cells. Degradation of plasma-membrane-derived GSLs in the lysosomes
      after internalization through the endocytic pathway is achieved through the
      concerted actions of hydrolysing enzymes and sphingolipid activator proteins. The
      latter are proteins necessary for the degradation of GSLs possessing short
      oligosaccharide chains. Some activator proteins bind to GSLs and form water
      soluble complexes, which lift out of the membrane and give the water-soluble
      hydrolysing enzymes access to the regions of the GSL that would otherwise be
      obscured by the membrane. The inherited deficiency of both lysosomal hydrolases
      and sphingolipid activator proteins gives rise to sphingolipid storage diseases.
      An analysis of these diseases suggests a new model for the topology of
      endocytosis and lysosomal digestion, which is discussed in this article.

PMID- 15157486
TI  - Cytoplasmic chaperones in precursor targeting to mitochondria: the role of MSF
      and hsp 70.
AB  - Despite extensive study since the early 1980s, the mechanism by which newly
      synthesized protein precursors are unfolded in the cytoplasm and targeted
      correctly to the mitochondrial surface prior to translocation through the
      mitochondrial membranes is understood poorly. Recently, an N-ethylmaleimide (NEM)
      sensitive cytoplasmic factor called mitochondrial import stimulation factor
      (MSF), which catalyses the ATP-dependent unfolding of precursor proteins, was
      described. Unlike the more general chaperone proteins of the hsp70 families, MSF
      not only unfolds proteins but also targets the unfolded precursor proteins to the
      mitochondria. Here, Mihara and Omura summarize what is known about MSF and
      speculate on how it, and other cytoplasmic factors, may be involved in
      mitochondrial import.

PMID- 15157487
TI  - Actin-based bacterial motility: towards a definition of the minimal requirements.
AB  - At the border line between microbiology and cell biology, the spectacular
      capacity o f some intracellular bacterial pathogens, including Listeria
      monocytogenes, Shigella flexneri and several Rickettsias, to use actin
      polymerization as a driving force for intracellular movement, cell-to-cell
      spreading and dissemination within the infected tissue is being increasingly
      studied. Now that it is possible to manipulate the bacterial surface proteins
      involved in this process - ActA o f L. monocytogenes and IcsA of S. flexneri -
      these bacterial systems are providing experimental models in which to investigate
      the role o f actin filament dynamics in cell motility.

PMID- 15157488
TI  - gamma-Tubulin and microtubule organization in plants.
AB  - In animal cells, microtubule assembly is usually initiated at one specialized
      structure, the centrosome. By contrast, in plant cells, microtubule assembly
      begins at a variety of locations within the cell. A member of the tubulin gene
      family, gamma-tubulin, is localized to the centrosome in animal cells and is
      important in the assembly of microtubules in vivo. Recent reports have identified
      gamma-tubulin genes in plants and have described the complex intracellular
      distribution of the encoded polypeptides. Here, Harish Joshi and Barry Palevitz
      comment upon how this information may help elucidate the organizing principles of
      the complex arrays of microtubules in plant cells.

PMID- 15157489
TI  - The membrane-recruitment-and-recycling hypothesis of gastric HCl secretion.
AB  - In the unstimulated oxyntic (or parietal) cell, the primary pump for gastric HCl
      secretion, the H+/K+-ATPase, is retained within the cytoplasm in a membranous
      compartment of tubulovesicles. Neural or hormonal stimulation of acid secretion
      induces extensive membrane transformations consistent with a fusion and
      recruitment of tubulovesicles to the apical plasma membrane. The consequent
      placement of H+/K+-ATPase in parallel with K(+) and Cl(-) channels provides the
      necessary ionic flow and ATP-driven exchange for net HCl secretion. Current
      evidence is consistent with a recruitment and recycling of membrane transporters,
      such as H+/K+-ATPase, through docking/fusion machinery analogous to that in many
      other systems.

PMID- 15157490
TI  - From coiled tubules to a secretory canaliculus: a new model for membrane
      transformation and acid secretion by gastric parietal cells.
AB  - The acid-secreting gastric parietal cell has a unique secretory membrane system.
      This membrane system exists in an inactive (non-secreting) and an active
      (secreting) form. The current accepted model to explain the transformation events
      associated with the conversion of the non-secreting membrane to the secreting
      membrane, and vice versa, invokes membrane recycling of elongated vesicle
      structures. However, recent studies employing cryopreparation have shown that the
      non-secreting membrane in these cells is actually a complex network of helically
      coiled tubules. Here, we present an alternative model to explain how the membrane
      in parietal cells is activated to secrete HCl.

PMID- 15157495
TI  - Mechanisms of protein import across the mitochondrial outer membrane.
AB  - Mitochondria import the majority of their proteins from the cytosol. At the
      mitochondrial outer membrane, import is initiated through a series of reactions,
      which include preprotein recognition, unfolding, insertion and translocation.
      These processes are facilitated by a multisubunit complex, the TOM complex.
      Specific roles can now be assigned to several components of this complex.
      Although the import machinery of the outer membrane can insert and translocate a
      few proteins on its own, completion of translocation o f most preproteins is
      dependent upon coupling to both the membrane potential and mt-Hsp70/ATP-driven
      transport across the inner membrane, mediated by the TIM complex.

PMID- 15157496
TI  - rum1: a CDK inhibitor regulating G1 progression in fission yeast.
AB  - In all eukaryotes, entry into mitosis from G2 phase is initiated by a complex of
      the cdc2 kinase and a B-type cyclin. It has now been shown that, in fission
      yeast, B-type cyclins also activate cdc2 in G1, thus governing cell-cycle
      commitment, as well as the onset of S phase. In this article, Karim Labib and
      Sergio Moreno review the evidence that ruml inhibits the kinase activity of cdc2
      associated with B-type cyclins and is an important regulator o f G1 progression
      in fission yeast.

PMID- 15157497
TI  - The role of nuclear import and export in influenza virus infection.
AB  - Infection with influenza virus involves a complex series of nuclear import and
      export events. Early in infection, incoming viral ribonucleoproteins (vRNPs) are
      imported into the nucleus. Later, viral transcripts are exported from the
      nucleus, newly synthesized structural proteins are transported back into the
      nucleus and, finally, newly assembled vRNPs are exported. All these import and
      export steps, and, in particular, the bidirectional traffic of vRNPs rely on the
      transport machinery of the cell, but are regulated both by viral and cellular
      factors. The viral MI protein serves as the master organizer in determining the
      directionality of vRNP transport.

PMID- 15157498
TI  - Communicate your science ! ... Super seminar slides.

PMID- 15157499
TI  - Microscopy animations on the web.

PMID- 15157500
TI  - 'Smoothening' the path for hedgehogs.
AB  - Studies of the HEDGEHOG signalling pathway in Drosophila have revealed a
      functional link between two genes, cubitus interruptus and patched, whose human
      homologues are, respectively, a proto-oncogene and a tumour suppressor. While the
      former has been implicated as a transcription factor, controversy has surrounded
      the function of the transmembrane protein encoded by the latter. Somewhere in the
      signal-transduction pathway between these two lies protein kinase A (PKA), and
      now SMOOTHENED, whose similarity to G-protein-coupled receptors suggests a link
      with PKA, has also been implicated in the pathway. This article summarizes the
      current understanding of the pathway and the interactions between these proteins.

PMID- 15157501
TI  - The role of vascular endothelial growth factor in blood vessel formation.
AB  - Angiogenic growth factors and their endothelial receptors function as signalling
      molecules during vascular growth and development. Vascular endothelial growth
      factor (VEGF) and its receptors represent a key regulatory system of embryonic
      vascular development and of both physiological and pathological
      neovascularization.

PMID- 15157502
TI  - Cell adhesion: integrating circuitry.

PMID- 15157503
TI  - Cell adhesion and angiogenesis.
AB  - Cell-adhesion mechanisms play a fundamental role during angiogenesis. This
      article summarizes the role of various cell-adhesive events in blood vessel
      formation, including general aspects of cell-matrix and cell-cell interactions.
      In particular, the authors discuss the role of integrin alphavbeta3 in vascular
      cell survival, proliferation and invasion during the complex process of
      angiogenesis.

PMID- 15157504
TI  - Traffic COPs and the formation of vesicle coats.
AB  - Forward and retrograde trafficking of secretory proteins between the endoplasmic
      reticulum and the Golgi apparatus is driven by two biochemically distinct vesicle
      coats, COPI and COPII. Assembly of the coats on their target membranes is thought
      to provide the driving force for membrane deformation and the selective packaging
      of cargo and targeting molecules into nascent transport vesicles. This review
      describes our current knowledge on these issues and discusses how the two coats
      may be differentially targeted and assembled to achieve protein sorting and
      transport within the early secretory pathway.

PMID- 15157505
TI  - Phospholipase D in vesicle budding.

PMID- 15157506
TI  - Stable intercellular bridges in development: the cytoskeleton lining the tunnel.
AB  - A wide variety of intercellular junctions that are involved with cell adhesion or
      signal transduction have been described in recent years. A widespread but less
      well-characterized type of intercellular junction is the stable intercellular
      bridge. Several organisms use stable intercellular bridges as cytoplasmic
      connections, probably to allow rapid transfer of information and organelles
      between cells. Here, the authors take a detailed look at the assembly of
      intercellular bridges called ring canals in the Drosophila germline and discuss
      how examination of mutants that disrupt Drosophila ovarian ring canal assembly
      indicates that these bridges are required for intercellular transport of
      cytoplasm.

PMID- 15157507
TI  - Growing up in a dangerous environment: a network of multiple targeting and
      folding pathways for nascent polypeptides in the cytosol.
AB  - The first events in the lives of proteins are the most hazardous. Starting at the
      ribosome, nascent polypeptides undergo complex folding processes endangered by
      aggregation reactions. Proteins with organellar destinations require correct
      targeting to the translocation machineries and prevention from premature folding.
      The high precision and speed of these processes is ensured by a cystosolic system
      consisting of molecular chaperones, folding catalysts and targeting factors. This
      review focuses on the interactions of this system with nascent polypeptides and
      discusses new concepts for protein folding in the cytosol. It is proposed that
      folding and targeting are promoted by a flexible network of multiple unassisted
      and assisted pathways.

PMID- 15157508
TI  - RNA: traffic report.

PMID- 15157509
TI  - Arabinogalactan-proteins: a class of extracellular matrix proteoglycans involved
      in plant growth and development.
AB  - Arabinogalactanproteins (AGPs) are proteoglycans of the extracellular matrix o f
      most plants. Since the late 1980s, AGPs have attracted widespread attention from
      plant biologists following reports of their involvement in plant development. In
      particular, the use of monoclonal antibodies to carbohydrate epitopes of AGPs has
      demonstrated stage- and tissue-specificity and has led to suggestions that they
      are involved in tissue morphogenesis. The recent cloning of the genes for several
      AGP protein backbones allows us to consider new strategies to address their
      function. Here, we summarize our knowledge of AGPs and consider parallels with
      animal proteoglycans as a possible framework for future work.

PMID- 15157510
TI  - Armadillo repeats in the SpKAP115 subunit of kinesin-II.

PMID- 15157511
TI  - Careers in science and engineering.

PMID- 15157512
TI  - A link between cell-surface receptors and ICE proteases.

PMID- 15157513
TI  - Molecular mechanisms of self-incompatibility in flowering plants and fungi -
      different means to the same end.
AB  - Hermaphrodite flowering plants and fungi face the same sexual dilemma - how to
      avoid self-fertilization. Both have evolved ingenious recognition systems that
      reduce or eliminate the possibility of selfing. These self-incompatibility (SI)
      systems offer unique opportunities to study recognition and signalling in non
      animal cells and also represent model systems for studying the evolution of
      breeding systems at a molecular level. In this review, the authors discuss recent
      molecular data that predict an astonishing diversity in the cellular mechanisms
      of SI operating in flowering plants and fungi.

PMID- 15157514
TI  - Synaptic proteins and the assembly of synaptic junctions.
AB  - Synapses are highly specialized contact sites between neurons and their target
      cells where information in the form of chemical substances travels from a pre- to
      a postsynaptic cell. In the central nervous system of mammals, most nerve cells
      are innervated by functionally distinct types of synapses, each requiring a
      specific set of molecular constituents for proper function. Various molecular
      players that may be involved in the assembly of synaptic junctions have been
      identified recently.

PMID- 15157515
TI  - Selection of polarized growth sites in yeast.
AB  - The budding yeast Saccharomyces cerevisiae responds to intracellular and
      extracellular cues to direct cell growth. Genetic analysis has revealed many
      components that participate in this process and has provided insight into the
      mechanisms by which these proteins function. Several of these components, such as
      the septins, pheromone receptors and GTPase proteins, have homologues in
      multicellular eukaryotes, suggesting that many aspects of polarized cell growth
      may be conserved throughout evolution. This review discusses our current
      understanding of the molecular mechanisms of growth-site selection during the
      different stages of the yeast life cycle.

PMID- 15157516
TI  - Chromophore-assisted laser inactivation (CALI): probing protein function in situ
      with a high degree of spatial and temporal resolution.

PMID- 15157517
TI  - The subunit-exchange model of histone acetylation.
AB  - Increased histone acetylation has long been linked to gene activation, but little
      is known about how acetylation levels are regulated, largely because the histone
      acetyltransferase activities (HATs) responsible for this modification have been
      cloned only recently. Comparison of the biochemical nature of the Tetrahymena HAT
      A complex with the genetic and biochemical properties of the Saccharomyces Gcn5p
      Ado complex leads us to propose that histone acetylase assemblies may be modular
      in nature and that this modularity may be an intimate part of the association of
      these enzymes with chromatin. The 'subunit-exchange' model provides a mechanism
      for the regulation and targeting of both histone acetylases and deacetylases and
      has implications for the control of cell growth, proliferation and tumorigenesis.

PMID- 15157518
TI  - Highly divergent Caenorhabditis and Saccharomyces tubulins evolved recently from
      genes encoding gamma-tubulin.

PMID- 15157520
TI  - Cortical domains and the mechanisms of asymmetric cell division.
AB  - Asymmetric cell divisions are central to the generation of cell-fate diversity
      because factors that are present in a mother cell and distributed unequally at
      cell division can generate distinct daughters. The process o f asymmetric cell
      division can be described as consisting of three steps: setting up an asymmetric
      cue in the mother cell, localizing factors with respect to this cue, and
      positioning the plane o f cell division so that localized factors are partitioned
      asymmetrically between daughters. This review describes how specialized cortical
      domains play a key role in each of these steps and discusses our current
      understanding of the molecular nature o f cortical domains and the mechanisms by
      which they may orchestrate asymmetric cell divisions.

PMID- 15157521
TI  - A question of balance: the role of cyclin-kinase inhibitors in development and
      tumorigenesis.
AB  - Cyclin-kinase inhibitors (CKIs) are versatile negative regulators of cell
      proliferation that function in developmental decisions, checkpoint control and
      tumour suppression. Phenotypic examination of mice lacking individual CKIs has
      begun to reveal the specialized roles that each of these proteins play in vivo.
      This review focuses on what has been learned about the role of CKIs in
      development and cancer through the generation of knockout animals. The authors
      discuss whether differences in knockout phenotypes between CKIs reflect
      differential use of these inhibitors by the organism or a fundamental difference
      between the inhibitors, and suggest a balance hypothesis to explain the different
      effects observed.

PMID- 15157522
TI  - Chemical inhibitors of cyclin-dependent kinases.
AB  - Transient activation o f cyclin-dependent kinases (CDKs) is responsible for
      transition through the successive phases of the cell-division cycle. Major
      changes in the expression and regulation of CDKs have been described in human
      tumours. Enzymatic screening is starting to uncover chemical inhibitors o f CDKs
      that arrest the cell cycle at various steps. This review summarizes our knowledge
      of the first generation inhibitors, their molecular mechanisms of action and
      their effects on the cell cycle and apoptosis, and discusses their potential as
      synchronizing agents, as ligands for affinity chromatography and as therapeutic
      agents.

PMID- 15157523
TI  - Sphingolipid synthesis and membrane formation by Plasmodium.
AB  - Plasmodium falciparum is a protozoan parasite that causes the most virulent o f
      human malarias. The asexual blood-stage organism invades and multiplies in a
      vacuole in the mature erythrocyte. During intravacuolar growth, it induces the
      formation of a novel network o f tubovesicular membranes, the TVM, that is not
      present in uninfected red blood cells. Recent data suggest that sphingomyelin
      biosynthesis by the parasite is an essential requirement for the assembly o f the
      TVM. Furthermore, sphingolipid synthesis as well as the formation and function o
      f the TVM may provide new targets for chemotherapy against malaria parasites.

PMID- 15157524
TI  - Insulin receptor substrate 1 and 2 (IRS1 and IRS2): what a tangled web we weave.
AB  - The insulin receptor is a transmembrane tyrosine kinase that is essential for
      mediating multiple intracellular signalling cascades that lead ultimately to the
      biological actions of insulin Tyrosine phosphorylation o f the cytosolic proteins
      insulin receptor substrate 1 and 2 (IRS1 and IRS2) produces protein 'scaffolding'
      for the assembly of effector proteins containing Src homology 2 (SH2) domains,
      thereby generating multisubunit signalling complexes. Although IRS1 was
      originally isolated as a specific insulin receptor substrate, both IRS1 and IRS2
      appear to play a broader role, functioning also as proximal substrates in growth
      hormone and cytokine receptor signalling. Current data establish IRS1 and IRS2 as
      critical effectors integrating various cell-type-specific signals into distinct,
      but overlapping, biological responses.

PMID- 15157525
TI  - Viruses: the Trojan horses of the cell.

PMID- 15157526
TI  - Portals of entry: uncovering HIV nuclear transport pathways.
AB  - The ability to infect non-dividing cells sets aside lentiviruses such as HIM from
      the animal onco-retroviruses which are only able to infect actively dividing
      cells. This difference in lentivirus and oncovirus biology can be attributed to
      the relative ability of the reverse transcription complex (preintegration
      complex) of the virus to enter the nucleus. For lentiviruses such as HIV, active
      transport processes facilitate this translocation. By contrast, nuclear membrane
      breakdown at mitosis is required before the reverse transcription complex o f
      onco-retroviruses can enter the nucleus. Several components o f the HIV reverse
      transcription complex that facilitate its nuclear transport have now been
      identified and an analysis o f these import factors is yielding insight into how
      opposing targeting functions o f viral proteins are regulated.

PMID- 15157527
TI  - Semaphorins: mediators of repulsive growth cone guidance.
AB  - During development, neuronal growth cones encounter a variety of guidance cues
      while mediating axon path finding, target recognition and synapse formation. It
      is clear that repulsive guidance mechanisms play an essential role in these
      processes. The semaphorin gene family, which is conserved from invertebrates to
      mammals, includes members that mediate repulsive guidance. Molecular and cellular
      analysis of this gene family is providing insight into how inhibitory cues
      function during neurodevelopment.

PMID- 15157528
TI  - Meiotic metaphase arrest in animal oocytes: its mechanisms and biological
      significance.
AB  - Metaphase arrest in meiosis I or II before fertilization is a common and unique
      feature of oogenesis in many animal species. How and why oocytes from many
      species are arrested at metaphase, rather than after the completion of meiosis,
      has long remained a mystery. This article reviews recent advances in our
      understanding of the mechanisms and biological significance of meiotic metaphase
      arrest in animal oocytes.

PMID- 15157529
TI  - Telomere functions: lessons from yeast.
AB  - Telomeres are specialized DNA protein structures that form the ends of eukaryotic
      chromosomes. In yeast, loss of even a single telomere causes a prolonged, but
      transitory, cell-cycle arrest. During this arrest, many broken chromosomes
      acquire a new telomere by one of three pathways, although at the cost of a
      partial loss of heterozygosity. In addition, a substantial fraction of the
      chromosomes lacking a telomere is lost, which generates an aneuploid cell. In
      these cases, the broken chromosome is usually replicated and segregated for ten
      or more cell divisions in unstable form. Extrapolation from yeast suggests that
      the gradual loss of telomeric DNA that accompanies ageing in humans may initiate
      the kinds of chromosomal rearrangements and genetic changes that are associated
      with tumorigenesis.

PMID- 15157530
TI  - Mitosis in motion.

PMID- 15157532
TI  - Microscopy and the world wide web.

PMID- 15157531
TI  - Communicate your science! ... Producing punchy posters.

PMID- 15157534
TI  - A simple scheme for probehead background suppression in one-pulse 1H NMR.
AB  - A very simple method for reducing probehead background signal in one-pulse 1H
      nuclear magnetic resonance (NMR) spectra is presented. Two one-pulse spectra are
      recorded, the first with pulse length tp1, the second with an L-times longer
      pulse, e.g. with L = 2. The second spectrum scaled by 1/L is subtracted from the
      first. Since the weak pulses experienced by spins outside the coil are in the
      linear regime, the background from outside the coil is effectively subtracted
      out. The background suppression efficiency is approximately 1.5b2, where b is the
      ratio of the B1 field inside the coil relative to that outside the coil.
      Experimentally, background suppression by at least a factor of 10 was achieved.
      Examples of background suppression in 1H wideline as well as 1H fast magic-angle
      spinning (MAS) one-pulse spectra of clay and polymer samples are shown.

PMID- 15157533
TI  - Molecular dynamics as studied by static-powder and magic-angle spinning 2H NMR.
AB  - The 2H NMR magic-angle spinning (MAS) technique is compared to the static-powder
      quadrupole echo (QE) and Jeener-Brockaert (JB) pulse sequences for a quantitative
      investigation of molecular dynamics in solids. The linewidth of individual
      spinning sidebands of the one-dimensional MAS spectra are observed to be
      characteristic of the correlation time from approximately 10(-2) to approximately
      10(-8) s so that the dynamic range is increased by approximately three orders of
      magnitude when compared to the QE experiment. As a consequence, MAS 2H NMR is
      found to be more sensitive to the presence of an inhomogeneous distribution of
      correlation times than the QE and JB experiments which rely upon lineshape
      distortions due to anisotropic T2 and T1Q relaxation, respectively. All these
      results are demonstrated experimentally and numerically using the two-site flip
      motion of dimethyl sulfone and of the nitrobenzene guest in the alpha-p-tert
      butylcalix[4]arene-nitrobenzene inclusion compound.

PMID- 15157535
TI  - A simple, inexpensive, and precise magic angle spinning speed controller.
AB  - Certain magic-angle spinning heteronuclear dipolar recoupling experiments using
      rotor-synchronized pulse trains require very precise control of the sample
      spinning rate. An inexpensive spinning speed controller for use in magic-angle
      solid-state NMR experiments is described which can control the spinning rate to
      within +/- 0.2 Hz. The apparatus is based on a simple micro-controller and is
      self-contained. Experimental results are presented that show the importance of
      good spinning speed control.

PMID- 15157537
TI  - Separation of aromatic-carbon 13C NMR signals from di-oxygenated alkyl bands by a
      chemical-shift-anisotropy filter.
AB  - Selection of alkyl-carbon and suppression of aromatic-carbon 13C nuclear magnetic
      resonance (NMR) signals has been achieved by exploiting the symmetry-based,
      systematic difference in their 13C chemical-shift anisotropies (CSAs). Simple
      three- or five-pulse CSA-recoupling sequences with "gamma-integral" cleanly
      suppress the signals of all sp2- and sp-hybridized carbons. The chemical-shift
      anisotropy-based dephasing is particularly useful for distinguishing the signals
      of di-oxygenated alkyl (O-C-O) carbons, found for instance as anomeric carbons in
      carbohydrates, from bands of aromatic carbons with similar 13C isotropic chemical
      shifts. The alkyl signals are detected with an efficiency of > 60%, with little
      differential dephasing. Combined with C-H dipolar dephasing, the CSA filter can
      identify ketal (unprotonated O-C-O) carbons unambiguously for the first time.
      Conversely, after short cross polarization and the CSA filter, O-CH-O (acetal)
      carbon signals are observed selectively. The methods are demonstrated on various
      model compounds and applied to a humic acid.

PMID- 15157538
TI  - The low-temperature 13C and 2H spectra and relaxation rates of methyl groups
      depend on the azimuth of B0 in the molecular frame. Those of 1H do not. Why?
AB  - It is shown that the answer to the question asked in the title is: Because the
      axial symmetry axes of the H-H dipolar coupling tensors in a -CH3 group are
      perpendicular to the (assumed) threefold axis of the group. By contrast, those of
      the 13C-H dipolar and 2H quadrupolar coupling tensors are not. The use of
      "symmetry adapted" spin functions and of a symmetry adapted form of the (dipolar)
      coupling Hamiltonian greatly simplifies the analysis.

PMID- 15157536
TI  - Molecular dynamics of amide ions in potassium amide (KNH2) studied with
      orientation-dependent deuterium spin lattice relaxation.
AB  - The reorientational molecular dynamics of the amide ions were investigated in
      three different phases of KND2 by means of 2H NMR line-shape analyses of solid
      echo, T1Z as well as T1Q distorted spectra in a temperature range of 80-420 K.
      The correlation times of the amide dynamics cover roughly eight decades in this
      temperature range. Due to the nonzero asymmetry parameter (eta approximately 0.2)
      of the electric field gradient tensor the calculation of the orientation
      dependent spectral densities Jm(theta, phi) required for the interpretation of
      the T1Z and T1Q distorted spectra cannot be simplified as in the case eta = 0 and
      a numerical approach was used for the calculation of Jm(theta, phi), which allows
      a maximum flexibility for simulating different models of motion. The amide ion
      dynamics in the low-temperature phase can be described as a superposition of a
      thermally activated large angle jump of the amide ions about their two-fold axes
      in an asymmetric four-well potential and strongly anisotropic molecular
      librations. The asymmetry of the potential surface of the jump process was found
      to be a function of temperature. Activation energy EA, attempt frequency tau0(-1)
      and DND bond angle epsilon were determined to 15.5(2) kJ/mol, 62(6) x 10(12) s(
      1) and 104.7(3) degrees. In the middle- and high-temperature phases the amide
      ions perform 90 degrees jumps about the crystallographic four-fold axes. For the
      high-temperature modification the correlation times were observed to follow an
      Arrhenius law with EA = 6.3(2) kJ/mol and tau0(-1) = 32(3) x 10(12) s(-1).

PMID- 15157539
TI  - Probing through bond connectivities with MQMAS NMR.
AB  - Polarization transfer from quadrupolar (27Al) to spin-1/2 (31P) nuclei via J
      coupling is employed to measure two-dimensional 27Al-31P heteronuclear
      correlation spectra with isotropic resolution. The proposed experiment, MQ-J
      HETCOR, uses multiple quantum magic angle spinning (MQMAS) NMR for elimination of
      the second-order quadrupolar broadening and INEPT, INEPTR, INEPT+ and DEPT
      sequences for the polarization transfer. The experimental conditions leading to
      best sensitivity and resolution are detailed using AlPO4-14 as a test sample.

PMID- 15157554
TI  - Interferences in hormone immunoassays.
AB  - Despite the numerous potential interferences that were discussed in this article,
      immunoassays, in general, are robust measurement systems. There is no practical
      way to identify specimens a priori that are likely to have immunoassay
      interference. Therefore, laboratories must rely on communication from clinicians
      to identify suspicious test values that may be caused by assay interference.
      After laboratories are alerted, multiple investigations can be undertaken. The
      common causes of immunoassay interferences (see Box I) are dependent on the
      analytic format. Competitive assays are most likely to have problems with cross
      reactivity, whereas immunometric assays most often have problems with heterophile
      antibodies. The simple steps to test for dilutional linearity, spiked recovery,
      heterophile antibody blocking,and testing with alternate technology can help in
      the evaluations of cases that are suspected to have assay interference.

PMID- 15157555
TI  - Thyroid disease: pathophysiology and diagnosis.
AB  - The thyroid is a butterfly-shaped gland that is located in the front of the neck
      just above the trachea; it weighs approximately 15 g to 20 g in the adult human.
      The thyroid produces and releases into the circulation at least two potent
      hormones, thyroxine (T4) and triiodothyronine (T3), that influence basal
      metabolic processes or enhance oxygen consumption in nearly all body tissues.
      Thyroid hormones also influence linear growth; brain function, including
      intelligence and memory; neural development; dentition; and bone development.

PMID- 15157556
TI  - Thyroglobulin: a specific serum marker for the management of thyroid carcinoma.
AB  - Thyroglobulin measurements in tissue and serum play an integral role in the
      evaluation of patients who have thyroid cancer. Immunohistochemical detection of
      thyroglobulin in surgical specimens is useful in the differential diagnosis of
      tumors of unknown origin; however, the most important application of
      thyroglobulin measurement in clinical practice is in the postsurgical management
      of differentiated thyroid cancer. Serum thyroglobulin is a highly specific and
      sensitive tumor marker for detecting persistent or recurrent thyroid cancer and
      for monitoring clinical status. The reappearance of circulating thyroglobulin
      after total thyroid ablation is pathognomonic for the presence of tumor. The
      measurement of thyroglobulin in serum is challenging, however, and several
      analytical problems limit assay performance. Thyroglobulin autoantibody
      interference is a particularly significant concern that requires all
      thyroglobulin samples to be screened for their presence. No immunoassay is
      totally free from interference by thyroglobulin autoantibodies. Measurement of
      thyroglobulin mRNA to detect circulating tumor cells may help to overcome some of
      the limitations of current protein-detection methods; serum thyroglobulin will
      continue to remain the "gold standard." The complex functional features of
      thyroid carcinomas make sole reliance upon any one diagnostic technique,
      including thyroglobulin assessments, potentially misleading. Thyroglobulin
      measurements are a critical component of a multifaceted diagnostic approach to
      this disease.

PMID- 15157557
TI  - Diagnosis and management of medullary thyroid carcinoma.
AB  - Successful treatment of MTC depends heavily on early diagnosis and treatment.
      Often, this is not possible for sporadic MTC; however, genetic testing for
      hereditary MTC makes this possible if genetic carriers have surgery before C
      cells undergo malignant transformation. All patients who have MTC should be
      tested for RET mutations, including putative sporadic cases. The leukocytes of
      suspected carriers and sporadic MTC cases should be tested for MEN2-associated
      germ-line mutations by polymerase chain reaction amplification of the appropriate
      RET gene exons, including 10, 11,13, 14, 15, and 16 (see Table I). When a RET
      mutation is found, all first-degree relatives must be screened to determine which
      individuals carry the gene. If these exons are negative, the other 15 should be
      sequenced because a small risk of hereditary MTC remains if no germ-line mutation
      is found. The probability that a first-degree relative will inherit an autosomal
      dominant gene for MTC from an individual who has sporadic MTC in whom no germ
      line mutation is found is 0.18% . Patients who have MEN2B or RET codon 883 or 918
      mutation should have a total thyroidectomy within the first 6 months of life,
      preferably within the first month of life. Patients who have 634 mutations, which
      account for approximately 70% of all MTC mutations, should undergo thyroidectomy
      by age 5 years. The recommendations for the timing of prophylactic thyroidectomy
      are not consistent for the less common mutations (see Table 2). There is a
      balance between performing prophylactic thyroidectomy earlier than at the
      youngest age at with MTC has been reported to occur for a specific RET mutation
      (see Fig. 3 and Table 2) and the complications of thyroidectomy, including
      permanent hypoparathyroidism and laryngeal nerve damage. Preoperative measurement
      of plasma free metanephrine and neck ultrasonography always should be done if the
      diagnosis of MTC is known preoperatively. Initial treatment of MTC is total
      thyroidectomy, regardless of its genetic type or putative sporadic nature,
      because surgery offers the only chance for a cure. Treatment with 1311 has no
      place in the management of MTC. Plasma CT measurements provide an accurate
      estimate of tumor burden and are especially useful in identifying patients who
      have residual tumor. Pentagastrin- or calcium-stimulated plasma CT testing is
      useful in identifying CCH or early MTC in carriers of RET mutations that are
      associated with late onset MTC. Pheochromocytoma may occur before or after MTC
      and is an important cause of mortality, even in young patients. HPT is an
      important aspect of MEN2A and requires surgery according to current guidelines
      for the management of primary HPT. Early thyroidectomy and appropriate management
      of pheochromocytoma clearly have modified the course of this disease, but more
      research is necessary in kindreds who have rare MTC mutations. Moreover, new
      treatments for widespread MTC are necessary because current chemotherapy agents
      offer little benefit. New drugs that lock the action of tyrosine kinase offer
      some hope.

PMID- 15157558
TI  - Advances in metanephrine testing for the diagnosis of pheochromocytoma.
AB  - Pheochromocytoma is a lethal tumor of chromaffin cells of the adrenal medulla
      that produces episodes of hypertension with the symptoms of palpitations, severe
      headaches, and sweating. The diagnosis of pheochromocytoma is a challenging one;
      autopsy series suggest that many pheochromocytomas are not clinically suspected,
      and the undiagnosed tumor can be associated with morbid consequences. The testing
      of catecholamines, metanephrines, and Vanillylymandelic acid commonly is used for
      screening of pheochromocytoma. The diagnostic value of various biochemical
      tests,as reported in recent Mayo and National Institutes of Health studies, have
      been compared and discussed in detail. The recent developments in the
      methodologies of metanephrines testing also are presented.

PMID- 15157560
TI  - Current controversies in testosterone testing: aging and obesity.
AB  - The interpretation of the total serum testosterone concentration is problematic
      because it is related directly to the serum SHBG concentration.Frequently, an
      estimate of the serum free testosterone concentration is obtained to better
      assess the clinical status of the patient. We reviewed five methods for the
      determination of free testosterone or a surrogate test/index and the problems
      with these methods. The calculated free testosterone or BAT (highly positively
      correlated) are recommended as the preferred tests to assess biologically-active
      testosterone, although interlaboratory values may differ because standards are
      not available. The controversies in evaluating gonadal function are illustrated
      by the andropause (elevated SHBG) and obese men (decreased SHBG).

PMID- 15157559
TI  - Steroid hormones: relevance and measurement in the clinical laboratory.
AB  - Steroid hormones are synthesized in the adrenal cortex, the gonads, and the
      placenta; are all derived from cholesterol and many are of clinical importance.
      This article addresses the relevance and methods of measurement of steroid
      hormones in the clinical laboratory.

PMID- 15157561
TI  - Rational use of the laboratory for childhood and adult growth hormone deficiency.
AB  - No laboratory test has sufficient diagnostic sensitivity and specificity to serve
      as a gold standard for the diagnosis for GHD: therefore, test results must be
      interpreted after assessment of risk for GHD is determined on clinical grounds.
      Growth data are particularly crucial for diagnosis of childhood GHD;history of
      known pituitary damage and presence or absence of other pituitary hormone
      deficiencies are the critical elements for the diagnosis of adult GHD. New
      reference preparations are available for GH and IGF-I and should greatly aid
      interassay comparisons when the preparations are universally adopted.GH
      stimulation testing remains a key part of the diagnosis of adult GHD, but is
      currently being de-emphasized for the diagnosis of pediatric GHD. Better
      interassay comparative data and organized clinical collaboration between
      clinicians and test manufacturers/laboratories to set rational clinical
      diagnostic cutoffs would improve greatly the clinical usefulness of GH
      stimulation testing. The availability of statistically sound age- and sex-related
      normative data for IGF-I and IGFBP3 make these key tests for the diagnosis of
      childhood GHD. Although IGF-I may not be a perfect test for the diagnosis of
      adult GHD, it may be sufficiently informative in many cases to warrant using it
      ona routine basis. IGF-I also has a role in monitoring the safety of adult
      patients who are on GH treatment; studies are underway to determine if IGF-I may
      be useful in the future for optimization of GH dosaging.

PMID- 15157562
TI  - The use of biochemical markers in osteoporosis.
AB  - Osteoporosis is a skeletal disease in which there is a loss of, or de-crease in,
      bone mass with a deterioration of the microarchitecture of bone tissue. The
      disease is progressive, taking place over a period of years, and involves
      derangements in the processes of bone turnover. These derangements can be
      classified as those in which osteoclast activity (resorption) is stimulated so
      that more bone is re-moved than formed or in which osteoblast activity
      (formation) is hindered such that refilling of the resorption cavity is
      incomplete. Regardless of the process, a key pathologic development is the net
      loss of bone mass. This article reviews the use of biochemical markers in
      osteoporosis.

PMID- 15157563
TI  - Measurement of parathyroid hormone and application of parathyroid hormone in
      intraoperative monitoring.
AB  - There has been a clear progression in assays for the analysis of PTH and its
      clinical applications. This includes the innovative use of PTH as a point-of-care
      assay as an intraoperative measure of the success of parathyroid surgery. The
      rapid PTH assay has served as a model for the development of other rapid hormone
      assays, such as for adrenocorticotropic hormone,although the clinical usefulness
      of these other applications is less well established. Knowledge of the
      circulating forms of PTH continues to progress. Information about the biologic
      and immunologic activities of these forms will aid in the interpretation and
      clinical use of current assays and in the development of new assays with improved
      specificities. The clinical laboratory will continue to play a vital role in
      providing testing and support for this important mediator of mineral metabolism.

PMID- 15157564
TI  - Adipocyte biology and adipocytokines.
AB  - Adipose tissue actively participates in regulation of food intake, energy
      expenditure, fuel metabolism, and a variety of other physiologic processes
      through its endocrine, paracrine, and autocrine secretory products (Table 4).
      Abnormal synthesis of these secretory products may be related to the pathogenesis
      of insulin resistance and its complications in patients who have adipose tissue
      disorders, such as obesity and lipodvstrophies.

PMID- 15157565
TI  - The role and assessment of ventricular peptides in heart failure.
AB  - Although heart failure may be diagnosed readily in its advanced stages, it may be
      difficult to diagnose clinically in its early stages.Thus, there is a critical
      need for an inexpensive, simple, rapid,and objective test for heart failure. This
      article discusses the role and assessment of ventricular natriuretic peptides and
      related pep-tides in heart failure.

PMID- 15157566
TI  - Endocrine autoantibodies.
AB  - The autoantibody assays that exist and that are being refined are of increasing
      importance to a broad spectrum of endocrine disorders. This is particularly true
      for type IA diabetes, which is one of the best-studied organ-specific autoimmune
      diseases. Autoantibodies are used as valuable markers in prediction and
      prevention studies of type IA diabetes. Autoantibodies related to other endocrine
      organs are also important because multiple related autoimmune endocrine and non
      endocrine disorders are increased in frequency in patients and their families
      with autoimmunity. The availability of highly sensitive and specific autoantibody
      assays for the various endocrine disorders can allow physicians to better
      diagnose and promptly treat these conditions.

PMID- 15157567
TI  - Autoimmune polyglandular syndrome type 1 and the autoimmune regulator.
AB  - The autoimmune polyglandular syndrome type I (APSI) is an auto-somal recessive
      disorder that is characterized by chronic mucocutaneous candidiasis, multiple
      autoimmune endocrinopathies, and ectodermal dystrophies. The gene that is
      responsible for APSI has been identified as autoimmune regulator (AIRE). More
      than 50 different mutations have been discovered in patients who have APSI and
      the defects include nonsense and missense mutations, small insertions and
      deletions that lead to frameshift, and splice site mutations. The 545-amino acid
      protein that is encoded by AIRE contains several structural motifs that are
      suggestive of a transcriptional regulator. We provide an overview of the clinical
      and genetic features ofAPSI as well as the structure and functions of the AIRE
      protein.

PMID- 15157570
TI  - The susceptibility of early developmental phases of an acid-tolerant and acid
      sensitive fish species to acidity and aluminum.
AB  - The mortality of roach (Rutilus rutilus) embryos increased during the early
      embryonic phase following exposure to Al and acidity from pH 6.7 to 5.0. No roach
      hatched at pH<5.00 or at pH 5.00 in the presence of Al. By contrast, increased
      embryonic mortality in pike (Esox lucius) occurred mainly during and after the
      normal hatching period due to the acidity-dependent prolongation and inhibition
      of hatching at pH 4.00. Newly hatched fry of both species were more sensitive to
      Al than the embryos. A reduction in the development of yolk-sac fry occurred in
      pike at pH 4.00 and in roach at pH 5.00, and in the presence of Al at pH< or
      =5.00 and pH< or =5.75, respectively. Thus, the most susceptible early
      developmental phase to acidity differed between the acid-sensitive roach and the
      acid-tolerant pike, although the newly hatched fry was the developmental phase
      most sensitive to Al for both species.

PMID- 15157569
TI  - The influence of nonylphenol on life-history of the earthworm Dendrobaena
      octaedra Savigny: linking effects from the individual- to the population-level.
AB  - We conducted a study to look at the effects of nonylphenol (NP) on the life
      history of the parthenogenetic earthworm, Dendrobaena octaedra. During a 196-day
      study, we observed that the growth rate of juveniles and the percentage of worms
      producing cocoons were the only traits significantly affected by NP, while the
      total number of cocoons produced was marginally affected. Despite some fairly
      large changes in the average values of individual life-history traits caused by
      NP, the effects were difficult to detect statistically due to large
      interindividual variability. A declining trend was observed for population growth
      rate (lambda) with increasing NP concentration, but the decline was not
      statistically significant. The percent reduction in lambda was less than the
      percent reduction in the most sensitive life-history trait (fecundity). An
      elasticity analysis showed that lambda was more sensitive to changes in survival
      than to changes in reproductive traits. However, neither juvenile nor adult
      survival were affected by NP, and decomposition analysis showed that the minor
      changes in lambda were mainly caused by effects of NP on time to first
      reproduction, time between reproduction events and fecundity. The present study
      suggests that extrapolation from laboratory studies to population effects in the
      field may be greatly enhanced by combining ecotoxicological and demographic
      methods.

PMID- 15157572
TI  - Effects of zearalenone on mRNA expression and activity of cytochrome P450 1A1 and
      1B1 in MCF-7 cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous pollutant and promoter
      of carcinogenesis with both estrogenic and antiestrogenic effects in mammal
      epithelium. Zearalenone (ZEA) is a naturally occurring estrogenic contaminant of
      moldy feeds and is present in high concentrations in dairy products and cereals.
      Numerous studies describe a possible correlation between xenoestrogens and breast
      cancer risk. A potential mechanism for the etiology of breast cancer involves
      altered cytochrome P450 (CYP) enzymes. Since cocontamination of multiple
      compounds in our environmental and occupational circumstances likely happens and
      since few studies have addressed the molecular consequences of combinations of
      contaminants, we decided to investigate the effects of ZEA on basal and TCDD
      induced mRNA expression and enzymic activity of CYP1A1 and CYP1B1 in human breast
      cancer MCF-7 cells. CYP1A1 enzyme activity was measured by the CYP1A1-referential
      activity assay, ethoxyresorufin O-deethylase (EROD), in MCF-7 cells. To
      investigate CYP1B1 activity, we employed the microsomal EROD assay prepared from
      baculovirus-infected insect cells expressing human cDNA CYP1B1. Reverse
      transcription-polymerase chain reaction was used to detect mRNA expression of
      CYP1A1 and CYP1B1 in MCF-7 cells. The results demonstrated that 10nM TCDD could
      readily induce a significant increase in the enzyme activity and mRNA expression
      of CYP1A1 in MCF-7 cells and 5 nM estradiol (E2) significantly reduced both basal
      and TCDD-induced activity and mRNA expression in MCF-7 cells. The same pattern
      was observed with 50nM ZEA. The estrogen receptor antagonist 4-hydroxytamoxifen
      could attenuate these inhibitive effects of both E2 and ZEA. Interestingly, Both
      E2 and ZEA could promote basal and TCDD-induced CYP1B1 activity but with no
      effect on CYP1B1 mRNA expression. These results suggest that the effect of ZEA on
      the TCDD-induced CYP1A1 activity and gene expression involved the estrogen
      receptor pathway and that the increase in the CYP1B1/CYP1A1 ratio underlying the
      basal or TCDD-treated condition might constitute one of the mechanisms underlying
      the synergic carcinogenic action of these compounds.

PMID- 15157571
TI  - A stream mesocosm study on the ecological effects of a C12-15 linear alcohol
      ethoxylate surfactant.
AB  - The responses of fish, invertebrates, and periphyton during a 56-day exposure to
      a C(12-15) linear alcohol ethoxylate surfactant were studied in stream mesocosms.
      An individual stream consisted of a slow-flowing pool section and a faster
      flowing riffle section. The surfactant has an average distribution of nine
      ethoxylate groups per mole of alcohol. Eight stream mesocosms were used to test
      the effects of seven concentrations of the surfactant. Time-averaged, mean,
      measured concentrations were 20, 40, 70, 160, 300, 390, and 740 microg/L, which
      represented 70-100% of nominal concentrations. The exposure of aquatic
      communities to the C(12-15)AE-9 surfactant in stream mesocosms resulted in no
      observed-effect concentrations (NOECs) for individual endpoints ranging from 160
      to 740 microg/L. Among the more sensitive responses were Oncorhynchus mykiss time
      to swim up and fry growth, abundance of juvenile Gammarus pulex in drift samples,
      Baetis abundance in the riffle sediment and in samples collected from tiles
      placed in the riffle, and Simulium density in the riffle tiles, all with NOECs of
      160 microg/L. Responses of the riffle sediment invertebrate assemblages assessed
      using multivariate methods support a NOEC of 160 microg/L. Abundances of G.
      pulex, Copepoda, and Agapetus sampled in the pools and pool tiles were not
      affected at the highest surfactant concentration tested after 56 days. Surfactant
      effects on periphyton and community leaf processing were seen at 300-390
      microg/L. Based upon the responses of several taxa representing different trophic
      levels, a mesocosm NOEC of 160 microg/L can be stated for the C(12-15)AE-9
      surfactant. This study provided additional data that can be used to reduce the
      uncertainty in extrapolating laboratory data to the field for the environmental
      risk assessment of alcohol ethoxylates.

PMID- 15157573
TI  - Genotoxic effects of cadmium chloride and azadirachtin treated singly and in
      combination in fish.
AB  - The genotoxic effects of cadmium chloride (CdCl(2)) and azadirachtin (Aza) were
      assessed singly and conjointly in a fish, Oreochromis mossambicus, with endpoints
      such as chromosome aberrations, abnormal red cell nuclei, abnormal sperm
      morphology, and protein content (both qualitative and quantitative) of selected
      tissues, namely, muscle, heart, eye, brain, gill, liver, spleen, and kidney. The
      primary objectives were, first, to examine if CdCl(2), a common pollutant, and
      Aza, a natural product of the neem plant used extensively as an 'ecofriendly'
      agent for many purposes, had any genotoxic effect of their own on nontarget
      aquatic organisms of economic importance; and second, if Aza could have any
      ameliorating effect on CdCl(2)-induced genotoxicity in O. mossambicus tissues. As
      compared with distilled water-treated controls, both CdCl(2) and Aza induced
      genotoxicity in O. mossambicus, the former in greater quantity than that produced
      by Aza. However, Cd-induced toxicity in O. mossambicus appeared to be ameliorated
      to some extent by Aza.

PMID- 15157574
TI  - Anguilla anguilla L. genotoxic and liver biotransformation responses to abietic
      acid exposure.
AB  - Adult eels (Anguilla anguilla L.) were exposed for 8, 16, 24, and 72 h to 0, 0.1,
      0.3, 0.9, and 2.7 microM abietic acid (AA). Genotoxicity was measured as
      erythrocytic nuclear abnormalities (ENA), as well as DNA strand breaks in blood
      and liver. Liver cytochrome P450 (P450) content, liver ethoxyresorufin O
      deethylase (EROD), and glutathione S-transferase (GST) activities were determined
      as biotransformation biomarkers. Liver alanine transaminase (ALT) activity was
      also measured as an indication of tissue damage. Low AA concentrations, such as
      0.1 and 0.3 microM, result in a delayed induction of A. anguilla L. liver EROD
      activity, whereas the higher AA concentration (2.7 microM AA) also has a delayed
      effect probably as a consequence of liver tissue high inhibitory concentration.
      The current eel liver GST activity results demonstrate that only low AA
      concentrations promote liver increases in GST, whereas high AA concentrations,
      such as 0.9 and 2.7 microM, do not alter it. The results concerning eel liver ALT
      activity indicate that significant liver damage is induced by high AA
      concentrations, such as 2.7 and 0.9 microM. The eel ENA result analysis reveals
      that AA is a weak ENA inducer in A. anguilla L. Blood DNA integrity results
      suggest that low AA concentrations promote late decreases in blood DNA integrity;
      nevertheless, high AA concentrations are early blood genotoxic inducers compared
      with low AA doses. According to the present research results with respect to eel
      liver DNA damage, all of the AA exposure concentrations decreased liver DNA
      integrity.

PMID- 15157575
TI  - Binary mixture of DDT and Arochlor1254: effects on sperm release by Danio rerio.
AB  - A long-term toxicity test with zebrafish was carried out with different
      concentrations of DDT, Arochlor1254 (A54), and their 1:1 mixture under flow
      through conditions. By collecting and counting the number of sperm released
      during separate mating events we observed that gametes are released
      asynchronously. Sperms are released in the form of sperm trails laid on the nest
      surface; subsequently active spermatozoa leave the trails and move in the water
      for several minutes. Sperm trails consist of bands of viscous material in which
      sperm are embedded. The water samples for the estimation of sperm presence were
      collected gradually within 180 min after 24 h, 2 weeks, 1 month, and 2 months of
      exposure. It was established that the reductions in count, activity of sperm, and
      average life span of sperm trails were significant (P<0.05) at the tested
      concentrations, 5 and 50 microg/L after 1 month and 2 weeks of exposure to each
      chemical tested and to their mixture, respectively. In conclusion, this study
      demonstrates that DDT and A54 could react synergically and increase the
      alteration in sperm release and activity as well as the life span of their
      trails.

PMID- 15157576
TI  - Effects of cypermethrin and carbofuran on certain hematological parameters and
      prediction of their recovery in a freshwater teleost, Labeo rohita (Hamilton).
AB  - Sublethal effects of cypermethrin and carbofuran on hematological parameters and
      their complete recovery were studied in Labeo rohita as a function of exposure
      time. Exposure of Labeo rohita to sublethal levels of cypermethrin and carbofuran
      resulted in significantly (P<0.05) lower values for erythrocyte count (RBC),
      hemoglobin content (Hb), and hematocrit compared with the control group. In
      contrast, there was a significant increase (P<0.05) in leukocyte count (TLC) in
      the pesticide-treated group. Mean cell volume (MCV) and mean cell hemoglobin
      (MCH) increased in response to both pesticides during the study. The rate of
      recovery or extrapolation time between Days 0 and 28 of the recovery period
      revealed that RBC completely recovered from cypermethrin toxicity on Days 80,
      86.6, and 90 and TLC recovered on Days 60, 62.7, and 63.3 in fish exposed to
      0.16, 0.40, and 0.80 microL/L cypermethrin, respectively. In the case of
      carbofuran toxicity, the complete recovery for RBC was on Days 100, 101.5, and
      102, and for TLC, on Days 77, 77.6, and 79.3 in fish exposed to 0.06, 0.15, and
      0.30 mg/L carbofuran, respectively. TLC recovered faster than RBC. RBC and TLC of
      fish exposed to carbofuran took more time to complete recovery than RBC and TLC
      in fish exposed to cypermethrin.

PMID- 15157577
TI  - Toxic effects of cypermethrin and alphamethrin on reproduction and oxidative
      metabolism of the freshwater snail, Lymnaea acuminata.
AB  - Effects of sublethal exposure to cypermethrin and alphamethrin on the
      reproductive physiology and oxidative metabolism of the freshwater snail, Lymnaea
      acuminata, were studied. Sublethal exposure to both pyrethroids caused increases
      in the numbers of egg masses and eggs at all concentrations, but the survival
      rate of the snails was significantly reduced 28 days after of hatching. Both
      pyrethroids altered the oxidative metabolism in hepatopancreas and ovotestis
      tissues of the snails. Stress conditions result in less availability of oxygen
      and in turn less ATP production in tissues, adversely affecting oxidative
      metabolism and reproduction in L. acuminata.

PMID- 15157578
TI  - Effects of cypermethrin on marine plankton communities: a simulated field study
      using mesocosms.
AB  - In earlier single-species toxicity tests we showed the negative effects on the
      calanoid copepod Acartia tonsa upon exposure to cypermethrin, a pesticide used in
      treatment for sea lice in salmon farming. In the present study we assessed
      effects at a higher level of biological organization and under a more realistic
      exposure scenario using mesocosms. The results showed that simulated field
      studies (SFSs) could be conducted with the mesocosms designed here. When
      cypermethrin was applied inside these mesocosms, its concentration decreased
      exponentially following a first-order kinetics model. The pesticide immediately
      reduced zooplankton density and biodiversity not only directly, by killing
      copepods, but also indirectly, by increasing the numbers of rotifers. Zooplankton
      density recovered after treatment, but zooplankton biodiversity remained altered.
      In an open environment, however, the rapid dissipation of the pesticide, coupled
      with population processes of compensation, migration, and immigration, may lead
      to recovery of the affected zooplankton communities.

PMID- 15157579
TI  - Long-term effects of fenoxycarb on two mayfly species in artificial indoor
      streams.
AB  - The effects of the juvenile hormone analog fenoxycarb (CAS No. 72490-01-8) were
      investigated in artificial indoor streams. The results from aufwuchs and two
      mayfly species (Rhithrogena semicolorata and Ephemerella ignita) are presented.
      Four concentrations ranging from 0.05 to 50 microg/L (with a spacing factor of
      10) were tested. Fenoxycarb disappeared rapidly from the water phase (DT(50)
      approximately 5 days in the highest concentration, less in the other
      concentrations). Physico-chemical parameters and aufwuchs were not affected by
      fenoxycarb. The mayfly R. semicolorata, introduced at the start of the
      experiment, was affected by treatments of 5 and 50 microg/L. For the larvae in
      the streams a LC(50) of 3.3 microg/L and for the larvae in the enclosures a
      LC(50) of 2.5 microg/L were calculated. The second species (E. ignita) was
      introduced 72 days after the application, at which time no fenoxycarb was
      detectable in the water of the streams (limit of detection of 0.5 ng/L). The
      emergence of E. ignita was affected in the highest treatment (50 microg/L).
      Ninety percent of the emerged imagoes showed morphological abnormalities at the
      abdomen.

PMID- 15157581
TI  - Polymetallic complexes in microemulsions for the hydrolysis of 4-nitrophenyl
      phosphate: a bio-mimetic model for decontamination of organophosphates in the
      environment.
AB  - Reactions of several metal ions and polymetallic complexes toward hydrolysis of 4
      nitrophenyl phosphate (NPP) were investigated at 10(-3)M concentration in oil-in
      water microemulsions and aqueous media. The reactions were monitored by measuring
      the absorbance of the nitrophenolate ion produced in the reaction aliquots with
      time. The order of effectiveness of the metal ions and polymetallic complexes at
      neutral pH toward hydrolysis of NPP was found to be Turnbull's
      Blue>magnetite>Fe(III)>Fe(II)>Co(II)>Ca(II)>Cu(II). The possible application of
      these systems for sites contaminated with chemical warfare agents such as
      organophosphates is discussed.

PMID- 15157580
TI  - Impact of nitrophenols on the photosynthetic electron transport chain and ATP
      content in Nostoc muscorum and Chlorella vulgaris.
AB  - Concentration-dependent inhibition of the photosynthetic electron transport chain
      (photosystem I (PS I), photosystem II (PS II) and whole chain reaction) and ATP
      content was observed in Nostoc muscorum and Chlorella vulgaris grown with o
      nitrophenol, m-nitrophenol, or 2,4-dinitrophenol. Although the extents of
      inhibition of the photosynthetic electron transport chain in both organisms were
      similar, PS II was more sensitive than PS I and whole chain reaction to the
      nitrophenols. Depletion of the ATP pool was noted in nitrophenol-grown cultures,
      probably as a consequence of nearly complete inhibition of the photosynthetic
      electron transport chain.

PMID- 15157582
TI  - Increasing allergy potency of Zinnia pollen grains in polluted areas.
AB  - There is much evidence that allergic symptoms represent a major health problem in
      polluted cities. The aim of this research is to elucidate some microscopic
      effects of air pollutants on pollen structure, proteins, and allergenicity. A
      scanning electron microscopy study of pollen grains indicated that in polluted
      areas, airborne particles accumulate on the surface of pollen grains and change
      the shape and tectum of pollen. Also, many vesicles are released from polluted
      pollen grains and the pollen material agglomerates on the surface of pollen
      grains. SDS-PAGE revealed that different proteins exist in mature and immature
      pollen grains. There were no significant differences between protein bands of
      polluted and nonpolluted pollen grains, but in polluted pollen, protein content
      decreases in response to air pollution, causing the release of pollen proteins.
      The results indicate that mature pollen have more allergenicity than immature
      pollen. According to the experiments polluted pollen grains are more effective
      than nonpolluted pollen grains in inducing allergic symptoms. Air pollutants can
      cause allergic symptoms, but when associated with allergen pollen grains, their
      allergenicity power is increased.

PMID- 15157583
TI  - Hematological changes due to chronic exposure to natural gas leakage in polluted
      areas of Masjid-i-Sulaiman (Khozestan province, Iran).
AB  - An overwhelming number of studies have given consistent findings that
      environmental or occupational exposure to oil products results in a significant
      decrease in circulating erythrocytes, hemoglobin, platelets, total white blood
      cells, and absolute numbers of lymphocytes and neutrophils. Some parts of Masjid
      i-Sulaiman (located in the southwest of Iran) are contaminated by subsurface
      leakage of natural gas, which contains a high level of hydrogen sulfide. The
      amount of all reactive sulfur compounds in air of contaminated areas of MIS was
      estimated as equal to 0.023+/-0.002 ppm of SO(2). In the present report the
      hematological findings of 99 persons from polluted areas of MIS were compared
      with those of 396 individuals from the general population of MIS matched by age
      (+/-3 years) and sex. The CBC test and the WBC differential were analyzed in one
      central laboratory according to standard hematological methods, by Coulter S
      (Biomedical). The multiple linear regression method was applied in order to
      detect differences among exposed and unexposed groups for hematological markers.
      The absolute mean number of red blood cells, percentages of hematocrit, level of
      hemoglobin, and absolute number of platelets were significantly higher among the
      exposed subjects compared with the control group. However, the absolute mean
      numbers of white blood cells, lymphocytes, and neutrophils were significantly
      decreased in the exposed group compared with the control.

PMID- 15157585
TI  - Drugs that affect the fetus and newborn infant via the placenta or breast milk.
AB  - In general, drugs that are taken by a mother during pregnancy or after birth may
      be transferred to the fetus or the infant (through breast milk). Many factors are
      involved that determine the amount of drugs that are transferred and their
      potential effects on the fetus or infant. A careful assessment of the risk versus
      benefit is necessary and should be individualized. In the breastfed infant, many
      measures can be undertaken further so that the amount of drug transferred to the
      infant is minimized.

PMID- 15157584
TI  - Suboptimal chlorine treatment of drinking water leads to selection of multidrug
      resistant Pseudomonas aeruginosa.
AB  - The present study was undertaken to investigate the spectrum of bacteria present
      in the River Gomti water before and after chlorination for drinking purposes. We
      observed that the strains of Pseudomonas aeruginosa that survived chlorination on
      three out of seven occasions were resistant to almost all the antibiotics tested.
      The chlorine-resistant bacteria had mucoid colonies and grew better at 24 degrees
      C. All attempts to isolate the plasmid responsible for chlorine resistance were
      unsuccessful. Laboratory experiments using different strains of the P. aeruginosa
      in distilled water showed that only the resistant strain survived chlorine
      treatment at a dose of < or =500 microg/L. Similar results were obtained when
      water collected from seven different sites on the River Gomti was treated with
      graded doses of chlorine. At the higher dose of chlorine, all the bacteria died
      in 30 min, whereas with lower doses all the bacteria survived. The present study
      underscores the importance of measuring water chlorine concentrations to assure
      they are sufficiently high to remove pathogenic bacteria from drinking water. To
      our knowledge, this is the first report in the literature of the selection of
      multidrug-resistant bacteria by suboptimal chlorine treatment of water.

PMID- 15157586
TI  - Preparing the neonate for transport.
AB  - Evaluation and stabilization of a neonate while arranging for neonatal transport
      are often stressful undertakings marked by urgency. Available resources may be
      limited, which further exacerbates anxiety of parents, staff, and physician. Even
      with limited resources, however, staff should be trained to evaluate and assess
      newborn babies and notify a physician quickly of any concerns. A preplanned
      transport algorithm gives a physician time to stabilize and manage the newborn
      while arranging for transport. Conditions that require neonatal transport are
      outlined, with a brief description of the subsequent hospital course, as
      anticipatory information for the parents.

PMID- 15157587
TI  - Discharge criteria for the term newborn.
AB  - The birthing process represents a traumatic eviction from the warm, quiet womb
      with a constant supply of food to the cold, bright world with nothing to eat.
      Tremendous physiologic strains are suddenly placed on the newborn infant. In a
      time frame of a few days, the neonate must transition successfully to
      extrauterine life, and the family must be prepared for the care of their newborn
      at home. This article reviews the physiologic and social issues that face the
      newborn and mother, discusses the specific issues created by early discharge, and
      provides suggested criteria for the timing of discharge of the well term neonate.

PMID- 15157588
TI  - Infants of diabetic mothers.
AB  - Advances in the management of the mother with diabetes have reduced the rate of
      morbidity and mortality for her infant. Aggressive control of maternal glycemic
      status is warranted, because most morbidities are epidemiologically and
      pathophysiologically closely linked to fetal hyperglycemia and hyperinsulinemia.
      The burgeoning public health problem of overweight and obesity in children will
      likely result in an increased incidence of metabolic syndrome X, characterized by
      insulin resistance and type II diabetes in adulthood. An early manifestation of
      this may be glucose intolerance during pregnancy in overweight women without
      diabetes. Clinicians must continue to have a high degree of suspicion for the
      diagnosis of diabetes during gestation and screen offspring of women with
      gestational diabetes for neonatal sequelae.

PMID- 15157590
TI  - Meconium stained fluid: approach to the mother and the baby.
AB  - Meconium aspiration syndrome is a common problem that most pediatricians will
      encounter in the delivery room and normal newborn nursery. Approximately 13% of
      all live births are complicated by meconium-stained amniotic fluid. Like many
      aspects of the perinatal period, optimal care of an infant born through meconium
      stained amniotic fluid involves collaboration between obstetrician and
      pediatrician, each with separate but important roles. As always, effective
      communication and advanced preparation and anticipation of potential problems
      form the cornerstone of this partnership. Together the health of infants may be
      improved.

PMID- 15157589
TI  - Abnormal fetal growth: intrauterine growth retardation, small for gestational
      age, large for gestational age.
AB  - The two extremes of abnormal fetal growth are restricted growth and excessive
      growth, both of which originate from alterations in the uterine metabolic milieu.
      The fetus must adapt to these conditions to survive. In both instances, however,
      the inciting insult and the subsequent adaptation of the fetus carry long-term
      health consequences. In some instances, these changes may have generational
      implications. Counseling and care by pediatricians should be directed at the
      continuum of age ranges, including the expectant mother, the newborn, the child
      and adolescent, and future generations.

PMID- 15157591
TI  - A consideration of neonatal resuscitation.
AB  - There are currently two major areas of resuscitation of the newborn which have
      come into question: the use of intermittent positive pressure ventilation and the
      use of oxygen. There is evolving evidence that volutrauma associated with IPPV,
      especially in the premature infant, may induce changes in the lung which can lead
      to chronic lung disease. There is reason to believe that the use of continuous
      positive airway pressure in premature infants who are making respiratory efforts
      may be less harmful than the use of IPPV. With regard to the use of oxygen, it is
      clear that most infants can be successfully resuscitated with room air. Although
      we can identify markers for oxidative stress in newborns when resuscitated with
      100% oxygen, the clinical importance of these markers remain an open issue. If
      the presence of these markers after resuscitation is shown to relate to clinical
      problems, then the use of oxygen may need to be considered.

PMID- 15157592
TI  - Early identification of infants at risk for developmental disabilities.
AB  - Early identification of infants at risk for developmental delay is of the utmost
      importance to initiate appropriate intervention. Although early detection can be
      a challenge, the primary care practitioner is in the ideal position to recognize
      and refer these children. Early recognition requires an in-depth knowledge of the
      child's history, general physical examination, and developmental level and an
      understanding of the expected developmental precursors of a skill. Referral to
      appropriate interventional resources leads to a formalized developmental and
      neurologic evaluation. If necessary, the development of an interdisciplinary
      comprehensive plan of remediation can occur and a definitive diagnosis can be
      made. If no significant problem is found, a decision to provide expectant
      observation is warranted.

PMID- 15157593
TI  - Differential diagnosis and management of neonatal hypoglycemia.
AB  - Persistent hypoglycemia in the neonate is most often caused by hyperinsulinemia.
      Recent discoveries in the molecular and biochemical regulation of insulin
      secretion have increased dramatically our understanding of disorders responsible
      for syndromes of hyperinsulinemic hypoglycemia. This article focuses on defects
      and disorders of the KATP channel, activating mutation of glucokinase and
      glutamate dehydrogenase, and other disorders that may be associated with specific
      phenotypes to permit appropriate targeted therapies. It is essential to evaluate
      these entities carefully because of the emerging evidence that at least half, if
      not more, have focal disease, which can be cured by local excision rather than
      diffuse disease, which may not be cured even after near total pancreatectomy with
      risk for future diabetes. Delay in diagnosis may be associated with developmental
      delay. The mechanisms of hypoglycemia remain incompletely understood.

PMID- 15157594
TI  - Neonatal hearing screening: to do or not to do.
AB  - Over the last two decades there has been a great deal of discussion concerning
      hearing loss in infants and the most appropriate diagnostic strategies to
      identify these children so that early intervention can be provided. This article
      reviews the developments that have transpired to allow universal newborn hearing
      screening programs to become the standard of care throughout most of North
      America. The article also examines ongoing controversies in universal newborn
      hearing screening and future needs to enhance universal newborn hearing
      screening, with the ultimate goal being early intervention for children
      identified with hearing loss through these programs.

PMID- 15157595
TI  - Low Apgar scores and the definition of birth asphyxia.
AB  - Nonreassuring fetal heart rate patterns, prolonged labor, meconium-stained fluid,
      a low 1-minute Apgar score, and mild to moderate acidemia have no predictive
      value for long-term neurologic injury without signs of encephalopathy and
      seizures. It is important to provide proper resuscitation, support infants, and
      allow time for evaluation. We have time and the tools to provide fairly
      predictive information to the families. It is important to use this knowledge
      wisely in communicating honestly with families, because difficult decisions
      undoubtedly will arise.

PMID- 15157596
TI  - Palliative care of the infant with lethal anomalies.
AB  - Although many families of infants with prenatally diagnosed lethal anomalies may
      receive counseling by clinicians with perinatal, neonatal, or genetic expertise
      and deliver their babies in a tertiary care center, pediatricians may be called
      on to support and care for these infants. Their involvement may begin prenatally,
      at the time of delivery, in the newborn nursery, or upon discharge home from a
      NICU. The goal of this article is to help the general pediatrician gain some
      comfort in knowing which cases might be considered and provide some tools and
      ideas for counseling a family from any point of involvement.

PMID- 15157597
TI  - The Baby-Friendly way: the best breastfeeding start.
AB  - In 1991, the World Health Organization and the United Nations Children's Fund
      launched the Baby-Friendly Hospital Initiative. "Baby-Friendly" is a designation
      that a hospital or birthing site can receive by demonstrating compliance with the
      "Ten Steps to Successful Breastfeeding." Baby-Friendly is more than a catchy name
      or a snappy slogan. With Baby-Friendly policies in place, breastfeeding
      initiation and duration rates increase and infant illness decreases. This article
      reviews the development of the Baby-Friendly Hospital Initiative, describes the
      components of the initiative, and evaluates current data that favor the universal
      implementation of the Baby-Friendly Hospital Initiative.

PMID- 15157598
TI  - The pediatrician's role in recognizing and intervening in postpartum depression.
AB  - Increasing evidence of postpartum depression is encouraging pediatricians to
      include screening and intervention for postpartum depression in standard newborn
      and infant care. Pediatricians have the most frequent exposure to mothers and
      infants in the most high-risk time period and they have a vested interest in the
      well-being of the child and mother. Because the time required to achieve basic
      screening and referral services is minimal, there is enough evidence that
      postpartum screening and intervention are crucial components of comprehensive
      newborn and infant care. It is incumbent upon pediatricians to screen for and
      intervene in cases of postpartum depression to provide thorough care for infants
      and their families.

PMID- 15157599
TI  - The call from the newborn screening laboratory: frustration in the afternoon.
AB  - Newborn screening programs in the United States are evolving in concert with
      technologic advances in analytic chemistry and medicine. Many more disorders are
      being identified on dried filter paper blood spots without fundamentally altering
      the basic principles first put forward in the 1960s. Some disorders have been
      added without researchers knowing if there is a true benefit to early diagnosis
      and treatment; some disorders currently being detected will merit little or no
      follow-up in the future. The general principles underlying newborn screening are
      discussed, as are the individual disorders screened in most programs. The
      expanding and evolving impact of tandem mass spectrometry on newborn screening is
      also explored.

PMID- 15157600
TI  - Anomalies, abnormalities, and care of the umbilicus.
AB  - This article discusses various anomalies and abnormalities of the umbilical cord
      and issues related to cord care. The issue of screening newborns with an isolated
      single umbilical artery for renal abnormalities is addressed. The clinical
      presentation of infants with omphalomesenteric and urachal duct remants along
      with the more common umbilical granuloma is reviewed. All three of these
      abnormalities can present with a wet or draining cord. The need for umbilical
      cord treatment with antimicrobial/antiseptic agents versus dry cord care is
      discussed, as are serious infections that involve the cord.

PMID- 15157602
TI  - Theoretical conformation of the closed and open states of the acetylcholine
      receptor channel.
AB  - We conduct a theoretical analysis to show the recently imaged structure of the
      acetylcholine receptor pore is in a non-conducting state. A hypothesised open
      state consistent with a lower resolution image is created and shown to have high
      conductance.

PMID- 15157603
TI  - Interaction of mitochondrial voltage-dependent anion channel from rat brain with
      plasminogen protein leads to partial closure of the channel.
AB  - Voltage-dependent anion channel (VDAC) is reported to be the receptor for
      plasminogen kringle5. In this paper, the interaction of VDAC from rat brain
      mitochondria with plasminogen protein has been investigated through bilayer
      electrophysiological studies. We report for the first time that interaction of
      plasminogen with VDAC leads to partial closure of the channel on a lipid bilayer.
      This could be a mechanism of modulation of VDAC gating in a cellular system.

PMID- 15157604
TI  - Targeting of proteins involved in sterol biosynthesis to lipid particles of the
      yeast Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, three enzymes of the sterol biosynthetic
      pathway, namely Erg1p, Erg6p and Erg7p, are located in lipid particles. Whereas
      Erg1p (squalene epoxidase) is also present in the endoplasmic reticulum (ER) to a
      significant amount, only traces of Erg6p (sterol C-24 methyltransferase) and
      Erg7p (lanosterol synthase) are found in the ER. We have chosen these three Erg
      proteins as typical representatives of lipid particle proteins to study targeting
      to their destination. Lipid particle proteins do not contain obvious targeting
      motifs, but the only common structural feature is the presence of one or two
      hydrophobic domains near the C-termini. We constructed truncated versions of
      Erg1p, Erg6p and Erg7p to test the role of these hydrophobic domains in
      subcellular distribution. Our results demonstrate that lack of the hydrophobic
      domains prevents at least in part the association of the proteins with lipid
      particles and causes their retention to the ER. This result strongly supports the
      view that ER and lipid particles are related organelles.

PMID- 15157605
TI  - Incorporation of the V-ATPase inhibitors concanamycin and indole pentadiene in
      lipid membranes. Spin-label EPR studies.
AB  - The incorporation of concanamycin A, a potent inhibitor of vacuolar ATPases, into
      membranes of dimyristoyl phosphatidylcholine has been studied by using EPR of
      spin-labelled lipid chains. At an inhibitor/lipid ratio of 1:1 mol/mol,
      concanamycin A broadens the chain-melting transition of the phospholipid bilayer
      membrane, and effects the lipid chain motion in the fluid phase. The outer
      hyperfine splitting of a spin label at the C-5 position and the line widths of a
      spin label at the C-14 position of the lipid chain are increased by concanamycin
      A. Considerably larger membrane perturbations are caused by equimolar admixture
      of a designed synthetic 5-(5,6-dichloro-2-indolyl)-2,4-pentadienoyl V-ATPase
      inhibitor. These results indicate that concanamycin A intercalates readily
      between the lipid chains in biological membranes, with minimal perturbation of
      the bilayer structure. Essentially identical results are obtained with
      concanamycin A added to preformed membranes as a concentrated solution in DMSO,
      or mixed with lipid in organic solvent prior to membrane formation. Therefore,
      the common mode of addition in V-ATPase inhibition assays ensures incorporation
      of concanamycin into the lipid bilayer milieu, which provides an efficient
      channel of access to the transmembrane domains of the V-ATPase.

PMID- 15157606
TI  - New insights into water-phospholipid model membrane interactions.
AB  - Modulating the relative humidity (RH) of the ambient gas phase of a
      phospholipid/water sample for modifying the activity of phospholipid-sorbed water
      [humidity-controlled osmotic stress methods, J. Chem. Phys. 92 (1990) 4519 and J.
      Phys. Chem. 96 (1992) 446] has opened a new field of research of paramount
      importance. New types of phase transitions, occurring at specific values of this
      activity, have been then disclosed. Hence, it is become recognized that this
      activity, like the temperature T, is an intensive parameter of the
      thermodynamical state of these samples. This state can be therefore changed
      (phase transition) either, by modulating T at a given water activity (a given
      hydration level), or, by modulating the water activity, at a given T. The
      underlying mechanisms of these two types of transition differ, especially when
      they appear as disorderings of fatty chains. In lyotropic transitions, this
      disordering follows from two thermodynamical laws. First, acting on the activity
      (the chemical potential) of water external to a phospholipid/water sample, a
      transbilayer gradient of water chemical potential is created, leading to a
      transbilayer flux of water (Fick's law). Second, water molecules present within
      the hydrocarbon region of this phospholipid bilayer interact with phospholipid
      molecules through their chemical potential (Gibbs-Duhem relation): the
      conformational state of fatty chains (the thermodynamical state of the
      phospholipid molecules) changes. This process is slow, as revealed by osmotic
      stress time-resolved experiments. In thermal chain-melting transitions, the first
      rapid step is the disordering of fatty chains of a fraction of phospholipid
      molecules. It occurs a few degrees before the main transition temperature, T(m),
      during the pretransition and the sub-main transition. The second step, less
      rapid, is the redistribution of water molecules between the different parts of
      the sample, as revealed by T-jump time-resolved experiments. Finally, in
      lyotropic and thermal transitions, hydration and conformation are linked but the
      order of anteriority of their change, in each case, is probably not the same. In
      this review, first, the interactions of phospholipid submolecular fragments and
      water molecules, in the interfacial and hydrocarbon regions of phospholipid/water
      multibilayer stacks, will be described. Second, the coupling of the
      conformational states of phospholipid and water molecules, during thermal and
      lyotropic transitions, will be demonstrated through examples.

PMID- 15157607
TI  - Variant glycosylation: an underappreciated regulatory mechanism for beta1
      integrins.
AB  - Although it has been known for many years that beta1 integrins undergo
      differential glycosylation in accordance with changes in cell phenotype, the
      potential role of N-glycosylation as a modulator of integrin function has
      received little attention. One reason for the relatively limited interest in this
      topic likely relates to the fact that much of the prior research was correlative
      in nature. However, new results now bolster the hypothesis that there is a causal
      relationship between variant glycosylation and altered integrin activity. In this
      review, the evidence for variant glycosylation as a regulatory mechanism for
      beta1 integrins are summarized, with particular emphasis on: (1). outlining the
      instances in which cell phenotypic variation is associated with differential
      beta1 glycosylation, (2). describing the specific alterations in glycan structure
      that accompany phenotypic changes and (3). presenting potential mechanisms by
      which variant glycosylation might regulate integrin function.

PMID- 15157609
TI  - Structural studies of the putative helix 8 in the human beta(2) adrenergic
      receptor: an NMR study.
AB  - The recently reported crystal structure of bovine rhodopsin revealed a
      cytoplasmic helix (helix 8) in addition to the seven transmembrane helices. This
      domain is roughly perpendicular to the transmembrane bundle in the presence of an
      interface and may be a loop-like structure in the absence of an interface.
      Several studies carried out on this domain suggested that it might act as a
      conformational switch between the inactive and activated states of this G-protein
      coupled receptor (GPCR). These results raised the question whether helix 8 may be
      an important feature of other GPCRs as well. To explore this question, we
      determined the structure of a peptide representing the putative helix 8 domain in
      another receptor that belongs to the rhodopsin family of GPCRs, the human beta(2)
      adrenergic receptor (hbeta(2)AR), using two-dimensional (1)H nuclear magnetic
      resonance (NMR). The key results from this structural study are that the putative
      helix 8 domain is helical in detergent and in DMSO while in water this region is
      disordered; the conformation is therefore dependent upon the environment.
      Comparison of data from five GPCRs suggests that these observations may be
      generally important for GPCR structure and function.

PMID- 15157608
TI  - Hydrocortisone and dexamethasone in very deformable drug carriers have increased
      biological potency, prolonged effect, and reduced therapeutic dosage.
AB  - We characterised biological properties of novel formulations of two low-potency
      glucocorticosteroids, dexamethasone and hydrocortisone, which have an equivalent
      dose ratio of 1:50 in vasoconstriction tests. The rate of such carrier-mediated,
      mainly non-diffusive glucocorticosteroids transport with very deformable lipid
      vesicles (Transfersomes) through the skin, and the corresponding cutaneous drug
      biodistribution data, were complemented with the drug bio-efficacy studies. The
      minimum effective drug dose that reduces arachidonic acid-induced murine ear
      oedema by 50% was used as one bioactivity indicator. The minimum drug amount
      ensuring such an effect in mouse skin decreases appreciably when a corticosteroid
      is applied epicutaneously with very deformable vesicles rather than a lotion or a
      creme. Specifically, the minimum effective dose for hydrocortisone in very
      deformable carriers is 2-3 microg cm(-2) whereas for the creme- or lotion-like
      preparations at least 10 microg cm(-2) is required. Such three- to fivefold
      relative increase of hydrocortisone potency is accompanied by at least 13%, and
      more often >20%, absolute drug potency enhancement. The delivery of
      hydrocortisone with very deformable carriers moreover prolongs the suppression of
      the drug-induced oedema nearly 2-fold (to approximately 24 h per application).
      The effective dose of dexamethasone delivered with very deformable vesicles into
      murine skin is reduced >10 times compared with the creme- or lotion-based
      products. Specifically, less than 0.1 microg cm(-2) dexamethasone in very
      deformable vesicles suppresses the arachidonic acid-induced murine ear oedema
      >50%, on the average. Dexamethasone use on the skin in such vesicles extends the
      duration of drug action fourfold, compared with a commercial creme, i.e. to >48 h
      per application. Epicutaneous use of glucocorticosteroids in very deformable
      vesicles also diminishes such drug's abrasion sensitivity and may increase the
      general robustness of drug effect. Lower frequency of skin treatment, which
      ensures adequate biological response, is a result of this. Topical corticosteroid
      delivery with very deformable vesicles, Transfersomes, thus improves the
      therapeutic risk-benefit ratio, arguably due to better targeting into and longer
      drug presence in the skin.

PMID- 15157610
TI  - Thermodynamic and mechanical properties of model mitochondrial membranes.
AB  - Cardiolipin is a unique four-tailed, doubly negatively charged lipid found
      predominantly within the inner mitochondrial membrane, and is thought to be
      influential in determining membrane potential and permeability. To determine the
      role of cardiolipin in modulating the properties of membranes, this study
      investigates the thermodynamics of mixed cardiolipin and phosphatidylcholine
      monolayers and bilayers. Gibbs free energy analysis of mixed monolayers indicates
      that at low cardiolipin concentrations (5-10 mol%), there is a positive deviation
      from ideality on a pure water subphase, while at physiological salt
      concentrations a negative deviation from ideality is observed. The mechanical
      properties of bilayers containing cardiolipin were measured using micropipette
      aspiration. Both apparent area compressibility modulus, as well as lysis tension,
      decrease with increasing cardiolipin content. This destabilization indicates a
      decrease in the cohesive energy of the membrane. This interplay between
      interactions of lipids in monolayers and bilayers, suggests cardiolipin plays a
      dual role in modulating membrane properties. Cardiolipin enhances lateral
      interactions between lipids within monolayer leaflets, while simultaneously
      decreasing the cohesive energy of membranes at physiologically relevant
      concentrations. Taken together, these findings correlate with the decreased
      permeability and creation of folds in the inner mitochondrial membrane.

PMID- 15157612
TI  - Investigation of the membrane localization and distribution of flavonoids by high
      resolution magic angle spinning NMR spectroscopy.
AB  - To investigate the structural basis for the antioxidative effects of plant
      flavonoids on the lipid molecules of cellular membranes, we have studied the
      location and distribution of five different flavonoid molecules (flavone,
      chrysin, luteolin, myricetin, and luteolin-7-glucoside) with varying polarity in
      monounsaturated model membranes. The investigated molecules differed in the
      number of hydroxyl groups attached to the polyphenolic benzo-gamma-pyrone
      compounds. To investigate the relation between hydrophobicity and membrane
      localization/orientation, we have applied (1)H magic angle spinning NMR
      techniques measuring ring current induced chemical shift changes, nuclear
      Overhauser enhancement cross-relaxation rates, and lateral diffusion
      coefficients. All investigated flavonoids show a broad distribution along the
      membrane normal with a maximum in the lipid/water interface. With increasing
      number of hydroxyl groups, the maximum of this distribution is biased towards the
      lipid headgroups. These results are confirmed by pulsed field gradient NMR
      measurements of the lateral diffusion coefficients of phospholipids and
      flavonoids, respectively. From the localization of different flavonoid protons in
      the membrane, a model for the orientation of the molecules in a lipid bilayer can
      be deduced. This orientation depends on the position of the polar center of the
      flavonoid molecule.

PMID- 15157611
TI  - Evidence for facilitated diffusion of urea across the gill basolateral membrane
      of the rainbow trout (Oncorhynchus mykiss).
AB  - Recent in vivo evidence suggests that the mechanism of branchial urea excretion
      in the ammoniotelic rainbow trout (Oncorhynchus mykiss) is carrier-mediated.
      Further characterization of this proposed mechanism was achieved by using an in
      vitro isolated basolateral membrane vesicle (BLMV) preparation in which isolated
      gill membranes were used to determine a variety of physiological properties of
      the transporter. BLMV demonstrated two components of urea uptake, a linear
      component at concentrations up to 17.5 mmol x l(-1) and a saturable component
      (K(0.5)=0.35+/-0.01 mmol x l(-1); V(max)=0.14+/-0.02 micromol mg protein(-1) h(
      1)) with a Hill constant of 1.35+/-0.18 at low, physiologically relevant urea
      concentrations (<2 mmol x l(-1)). Saturable uptake of urea at 1 mmol x l(-1) by
      BLMV was reduced by 88.5% when incubated with 0.25 mmol x l(-1) phloretin, a
      potent blocker of UT-type facilitated diffusion urea transport mechanisms. BLMV
      also demonstrated differential handling of urea versus urea analogues at 1 mmol x
      l(-1) concentrations and total analogue/total urea uptake ratios were 32% for
      acetamide and 84% for thiourea. Saturable urea uptake at 1 mmol x l(-1) was
      significantly reduced by almost 100% in the presence of 5 mmol x l(-1) thiourea
      but was not affected by 5 mmol x l(-1) acetamide or 5 mmol x l(-1) N-methylurea.
      Lastly, total urea uptake at 1 mmol x l(-1) by BLMV was sensitive to temperatures
      above and below the temperature of acclimation with a Q(10)>2 suggesting a
      protein carrier-mediated process. Combined, this evidence indicates that a
      facilitated diffusion urea transport mechanism is likely present in the
      basolateral membrane of the rainbow trout gill.

PMID- 15157613
TI  - Mechanism of formation of multilayered 2D crystals of the enzyme IIC-mannitol
      transporter.
AB  - We have recently reported the crystallization by reconstitution into lipid
      bilayer structures of Enzyme IIC(mtl), the transmembrane C-domain of the mannitol
      transporter from E. coli. The projected structure was determined to a resolution
      of 0.5 nm [J. Mol. Biol. 287 5 (1999) 845]. However, further investigation proved
      that these crystals were multilamellar stacks instead of 2D crystals, and
      therefore were unsuitable for three-dimensional structural analysis by electron
      crystallography. Understanding the crystallogenesis of these crystals could
      reveal the mechanism of formation of multilayers. In the present study, cryo
      electron microscopy (cryo-EM) and turbidimetry are used to study the successive
      steps of reconstitution of Enzyme IIC(mtl) into phospholipid-containing
      structures and its crystallization under different conditions. Our experimental
      approach enabled us to distinguish the separate steps of reconstitution and
      crystallization. The salt concentration especially influenced the nature of the
      vesicles, either half open unilamellar or aggregated multilamellar, formed during
      reconstitution of Enzyme IIC(mtl). The presence of DOPE and DOPC and the
      temperature influenced the type of lipid structures that were formed during the
      crystallization phase of Enzyme IIC(mtl). Cryo-EM showed that protein
      crystallization is closely associated with the formation of isotropic lipid
      (cubic) phases. We believe that DOPE is responsible for the formation of these
      lipid cubic phases, and that crystallization is driven by exclusion of protein
      from these phases and its concentration into the lamellar phases. This mechanism
      is inextricably associated with the formation of multilayers.

PMID- 15157614
TI  - Molecular cloning and localization of a PMCA P-type calcium ATPase from the coral
      Stylophora pistillata.
AB  - Plasma-membrane calcium pumps (PMCAs) are responsible for the expulsion of Ca(2+)
      from the cytosol of all eukaryotic cells and are one of the major transport
      systems involved in long-term regulation of resting intracellular Ca(2+)
      concentration. An important feature of stony corals, one of the major groups of
      calcifying animals, is the continuous export of large quantities of Ca(2+) for
      skeletogenesis. Here, we report the cloning and functional expression of the
      stpPMCA gene from the coral Stylophora pistillata, and whose features resemble
      those of the plasma-membrane Ca(2+)-ATPase family of mammalian cells. This is the
      first known example of a Ca(2+)-ATPase from the phylum Cnidaria, and thus, the
      most phylogenetically distant PMCA sequence in the animal kingdom described to
      date. We demonstrate that the localization of stpPMCA within calicoblastic cells
      is fully coherent with its role in calcification. We also show that the coral
      Ca(2+) pump is more closely related to vertebrate PMCAs than to Caenorhabditis
      elegans PMCAs. The cloning of evolutionarily conserved genes from cnidarian
      species repeatedly shows that these genes encode similar functional domains.
      Moreover, this high level of gene conservation further validates the use of
      cnidarian model systems for studying processes shared by Eumetazoans.

PMID- 15157615
TI  - Transfection efficiency and cytotoxicity of cationic liposomes in salmonid cell
      lines of hepatocyte and macrophage origin.
AB  - The transfection efficiency of liposome-based DNA formulations was studied in
      different salmonid cell lines of hepatocyte and macrophage origin. Parallel
      assessment of cell viability was carried out to define the balance between
      transfection efficiency and toxicity. For all cell lines, transfection efficiency
      varied with the lipoplex charge ratio and the amount of DNA added to the
      liposomes. The hepatocyte-derived cell line was most readily transfected while
      lower transfection efficiency was observed for the macrophage cell lines. The
      cationic liposomes showed a dose-dependent toxicity and were found to be most
      toxic for cells of macrophage origin. This was in line with the observation that
      higher amounts of lipids were associated with the cells of macrophage origin than
      the hepatocytes. Complexing DNA with the liposomes reduced the toxicity for all
      three cell lines, most markedly, however, for macrophage cell lines. The
      differences in the transfection and toxicity patterns between the cell lines are
      probably caused by differences in membrane composition as well as differences in
      phagocytic activity and processing of the liposomes/lipoplexes.

PMID- 15157616
TI  - Preparation and stability of lipid-coated nanocapsules of cisplatin: anionic
      phospholipid specificity.
AB  - Cisplatin nanocapsules represent a novel lipid formulation of the anti-cancer
      drug cis-diamminedichloroplatinum(II) (cisplatin), in which nanoprecipitates of
      cisplatin are coated by a phospholipid bilayer consisting of a 1:1 mixture of
      zwitterionic phosphatidylcholine (PC) and negatively charged phosphatidylserine
      (PS). Cisplatin nanocapsules are characterized by an unprecedented cisplatin-to
      lipid ratio and exhibit increased in vitro cytotoxicity compared to the free drug
      [Nat. Med. 8, (2002) 81]. In the present study, the stability of the cisplatin
      nanocapsules was optimized by varying the lipid composition of the bilayer coat
      and monitoring in vitro cytotoxicity and the release of contents during
      incubations in water and in mouse serum. The release of cisplatin from the PC/PS
      (1:1) nanocapsules in water increased with increasing temperature with a t(1/2)
      of 6.5 h at 37 degrees C. At 4 degrees C, cisplatin was retained in the
      nanocapsules for well over 8 days. Replacement of PS by either
      phosphatidylglycerol or phosphatidic acid revealed that nanocapsules prepared of
      PS were more stable, which was found to be due to the ability of PS to form a
      stable cisplatin-PS coordination complex. Mouse serum had a strong destabilizing
      effect on the cisplatin nanocapsules. The PC/PS formulation lost over 80% of
      cisplatin within minutes after resuspension in serum. Incorporation of
      poly(ethylene glycol 2000) (PEG)-derivatized phosphatidylethanolamine and
      cholesterol in the bilayer coat extended the lifetime of the cisplatin
      nanocapsules in mouse serum to almost an hour. The results demonstrate that
      specificity in the interaction of cisplatin with anionic phospholipids is an
      important criterium for the formation and stability of cisplatin nanocapsules.

PMID- 15157617
TI  - The role of lipid charge density in the serum stability of cationic lipid/DNA
      complexes.
AB  - To evaluate the role of lipid charge density in the serum stability of DOTAP
      Chol/DNA complexes (lipoplexes), lipid-DNA interactions, extent of aggregation,
      supercoil content, and in vitro transfection efficiency of lipoplexes were
      investigated. In general, higher serum concentration destabilized, and increasing
      molar charge ratio of DOTAP to negatively charged phosphates in the DNA
      (DOTAP(+)/DNA(-)) stabilized lipoplexes in serum as assessed by the criteria used
      in this study. The increase of cholesterol content led to increased serum
      stability, and DOTAP:Chol (mol/mol 1:4)/DNA lipoplex with DOTAP(+)/DNA(-) ratio 4
      was the most serum stable formulation of all the formulations examined, and
      maintained lipid-DNA interactions, did not aggregate and exhibited high in vitro
      transfection efficiency in 50% (v/v) serum. The increased stability of this
      formulation could not be explained by the decreased charge density of the lipid
      component. Furthermore, no single parameter examined in the study could be used
      to consistently predict the in vitro transfection efficiency of lipoplexes in
      serum. Surprisingly, no correlation between the maintenance of supercoiled DNA
      content and in vitro transfection efficiency was found in the study.

PMID- 15157618
TI  - Targeting of immunoliposomes to endothelial cells using a single-chain Fv
      fragment directed against human endoglin (CD105).
AB  - We generated immunoliposomes targeting proliferating endothelial cells by
      chemically coupling a single-chain Fv fragment (scFv A5) directed against human
      endoglin to the liposomal surface. For this purpose, we introduced an additional
      cysteine residue at the C-terminus of the scFv fragment. This scFv' fragment was
      expressed in soluble form in bacteria and allowed for a site-directed coupling to
      sulfhydryl-reactive lipids incorporated into the lipid bilayer. The
      immunoliposomes (ILA5) showed rapid and strong binding to human endoglin
      expressing endothelial cells (HUVEC, HDMEC), while no binding was observed with
      various endoglin-negative cell lines and blood lymphocytes. In vitro, ILA5 were
      stable for several hours in serum- or plasma-containing medium. Incubation of
      endothelial cells with ILA5 at 37 degrees C led to increased binding and
      internalisation of the liposomes as evidenced by a perinuclear accumulation. In
      vitro, doxorubicin-loaded ILA5 showed an increased cytotoxicity towards
      endothelial cells compared to untargeted liposomes and free doxorubicin. Since
      the vasculature of tumours is easily accessible to drug carrier systems, the
      described endothelial cell-specific immunoliposomes may be useful for the
      development of efficacious and safe vascular targeting agents in cancer therapy.

PMID- 15157619
TI  - Drug release rate influences the pharmacokinetics, biodistribution, therapeutic
      activity, and toxicity of pegylated liposomal doxorubicin formulations in murine
      breast cancer.
AB  - The pharmacokinetics (PK), biodistribution (BD), and therapeutic activity of
      pegylated liposomal doxorubicin formulations with different drug release rates
      were studied in an orthotopic 4T1 murine mammary carcinoma model. The focus of
      these experiments was to study the effects of different release rates on the
      accumulation of liposomal lipid and doxorubicin (DXR) into the tumor and
      cutaneous tissues of mice (skin and paws). These tissues were chosen because the
      clinical formulation of pegylated liposomal doxorubicin (Caelyx)/Doxi) causes
      mucocutaneous reactions such as palmar-plantar erythrodysesthesia (PPE).
      Liposomes with different doxorubicin (DXR) leakage rates were prepared by
      altering liposome fluidity through changing the fatty acyl chain length and/or
      degree of saturation of the phosphatidylcholine component of the liposome.
      Liposomes with fast, intermediate, and slow rates of drug release were studied.
      The plasma PK of the liposomal lipid was similar for all formulations, while the
      plasma PK of the DXR component was dependent on the liposome formulation.
      Liposomal lipid accumulated to similar levels in tumor and cutaneous tissues for
      all three formulations tested, while the liposomes with the slowest rates of DXR
      release produced the highest DXR concentrations in both cutaneous tissues and in
      tumor. Liposomes with the fastest drug release rates resulted in low DXR
      concentrations in cutaneous tissues and tumor. The formulation with intermediate
      release rates produced unexpected toxicity that was not related to the lipid
      content of the formulation. The liposomes with the slowest rate of drug leakage
      had the best therapeutic activity of the formulations tested.

PMID- 15157620
TI  - Electron holography of non-stained bacterial surface layer proteins.
AB  - We report transmission electron microscopy (TEM) investigations on bacterial
      surface layers (S-layers) which belong to the simplest biomembranes existing in
      nature. S-layers are regular 2D protein crystals composed of single protein or
      glycoprotein species. In their native form, S-layers are weak phase objects
      giving only poor contrast in conventional TEM. Therefore, they are usually
      examined negatively stained. However, staining with heavy metal compounds may
      cause the formation of structural artefacts. In this work, electron microscopy
      studies of non-stained S-layers of Bacillus sphaericus NCTC 9602 were performed.
      Compared to other proteins, these S-layers are found relatively stable against
      radiation damage. Electron holography was applied where information about phase
      and amplitude of the diffracted electron wave is simultaneously obtained. In
      spite of small phase shifts observed, the phase image reconstructed from the
      hologram of the non-stained S-layer is found to be sensitive to rather slight
      structure and thickness variations. The lateral resolution, obtained so far, is
      less than that of conventional electron microscopy of negatively stained S
      layers. It corresponds to the main lattice planes of 12.4 nm observed in the
      reconstructed electron phase image. In addition, as a unique feature of electron
      holography the phase image provides thickness information. Thus, the existence of
      double layers of the protein crystals could be easily visualized by the height
      profile of the specimen.

PMID- 15157621
TI  - Cholesterol modulates ligand binding and G-protein coupling to serotonin(1A)
      receptors from bovine hippocampus.
AB  - The serotonin(1A) (5-HT(1A)) receptor is an important member of the superfamily
      of seven-transmembrane domain G-protein-coupled receptors. We have examined the
      modulatory role of cholesterol on the ligand binding activity and G-protein
      coupling of the bovine hippocampal 5-HT(1A) receptor by depleting cholesterol
      from native membranes using methyl-beta-cyclodextrin (MbetaCD). Removal of
      cholesterol from bovine hippocampal membranes using varying concentrations of
      MbetaCD results in a concentration-dependent reduction in specific binding of the
      agonist 8-OH-DPAT to 5-HT(1A) receptors. This is accompanied by alterations in
      binding affinity and sites obtained from analysis of binding data. Importantly,
      cholesterol depletion affected G-protein-coupling of the receptor as monitored by
      the GTP-gamma-S assay. The concomitant changes in membrane order were reported by
      changes in fluorescence polarization of membrane probes such as DPH and TMA-DPH,
      which are incorporated at different locations (depths) in the membrane.
      Replenishment of membranes with cholesterol led to recovery of ligand binding
      activity as well as membrane order to a considerable extent. Our results provide
      evidence, for the first time, that cholesterol is necessary for ligand binding
      and G-protein coupling of this important neurotransmitter receptor. These results
      could have significant implications in understanding the influence of the
      membrane lipid environment on the activity and signal transduction of other G
      protein-coupled transmembrane receptors.

PMID- 15157622
TI  - Anionic amphiphile and phospholipid-induced conformational changes in human
      neutrophil flavocytochrome b observed by fluorescence resonance energy transfer.
AB  - The integral membrane protein flavocytochrome b (Cyt b) comprises the catalytic
      core of the human phagocyte NADPH oxidase complex and serves to initiate a
      cascade of reactive oxygen species that participate in the elimination of
      infectious agents. Superoxide production by the NADPH oxidase complex has been
      shown to be specifically regulated by the enzymatic generation of lipid second
      messengers following phagocyte activation. In the present study, a Cyt b-specific
      monoclonal antibody (mAb 44.1) was labeled with Cascade Blue (CCB) and used in
      resonance energy transfer (RET) studies probing the effects of a panel of lipid
      species on the structure of Cyt b. The binding of CCB-mAb 44.1 to immunoaffinity
      purified Cyt b was both highly specific and resulted in significant quenching of
      the steady state donor fluorescence. Titration of the CCB-mAb 44.1:Cyt b complex
      with the anionic amphiphile lithium dodecyl sulfate (LDS) resulted in a saturable
      relaxation of fluorescence quenching due to conformational changes in Cyt b at
      concentrations of the amphiphile required for maximum rates of superoxide
      production by Cyt b in cell-free assays. Similar results were observed for the
      anionic amphiphile arachidonic acid (AA), although no relaxation of fluorescence
      quenching was observed for arachidonate methyl ester (AA-ME). Saturable
      relaxation of fluorescence quenching was also observed with the anionic, 18:1
      phospholipids phosphatidic acid (DOPA) and phosphatidylserine (DOPS), while no
      relaxation was observed upon addition of the neutral 18:1 lipids
      phosphatidylcholine (DOPC), phosphatidylethanolamine (DOPE) or diacylglycerol
      (DAG) at similar levels. Further examination of a variety of phosphatidic acid
      (PA) species demonstrated DOPA to both potently induce conformational changes in
      Cyt b and to cause more dramatic conformational changes than PA species with
      shorter, saturated acyl chains. The data presented in this study support the
      hypothesis that second messenger lipids, such as AA and PA, directly bind to
      flavocytochrome b and modulate conformational states relevant to the activation
      of superoxide production.

PMID- 15157623
TI  - Intestinal zinc uptake in freshwater rainbow trout: evidence for apical pathways
      associated with potassium efflux and modified by calcium.
AB  - Understanding the mechanisms of intestinal zinc uptake in fish is of considerable
      interest from both nutritional and toxicological perspectives. In this study,
      properties of zinc transport across the apical membrane of freshwater rainbow
      trout intestinal epithelia were examined using right-side-out brush border
      membrane vesicles (BBMV's). Extravesicular calcium was found to have complex
      actions on zinc uptake. At a low zinc concentration of 1 microM, calcium (0.1-2
      mM) significantly stimulated zinc uptake. In contrast, calcium inhibited zinc
      uptake at higher zinc levels (100 microM). Lanthanum and cadmium in the external
      medium did not block zinc uptake, suggesting that interactions between zinc and
      calcium were not exerted at a calcium channel. Copper also failed to exercise any
      inhibitory action. Zinc association with the BBMV's was enhanced by an outward
      potassium gradient. This stimulatory effect was only present at a zinc
      concentration of 100 microM. The potassium channel blocker, tetraethylammonium
      chloride inhibited zinc uptake at this relatively high zinc concentration,
      suggesting the presence of a low affinity zinc uptake pathway linked to potassium
      efflux. The present study provides evidence that the mechanism of intestinal zinc
      uptake in rainbow trout is pharmacologically very different from that of the
      piscine gill and the mammalian intestine.

PMID- 15157624
TI  - Characterization of the main transition of dinervonoylphosphocholine liposomes by
      fluorescence spectroscopy.
AB  - The structural dynamics of the main phase transition of large unilamellar
      dinervonoylphosphocholine (DNPC) vesicles was investigated by steady state and
      time-resolved fluorescence spectroscopy of the membrane incorporated fluorescent
      lipid analog, 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine
      (PPDPC). These data were supplemented by differential scanning calorimetry (DSC)
      and fluorescence anisotropy measured for 1-palmitoyl-2-(3-(diphenylhexatrienyl)
      propanoyl)-sn-glycero-3-phosphocholine (DPHPC). The collected data displayed
      several discontinuities in the course of the main transition and the
      pretransition. The discontinuities seen in the fluorescence properties may
      require modification of the existing models for phospholipid main transition as a
      first order process. From our previous study on dipalmitoylphosphocholine (DPPC),
      we concluded the transition to involve a first-order process resulting in the
      formation of an intermediate phase, which then converts into the liquid
      crystalline state by a second order process. Changes in the physical properties
      of the DNPC matrix influencing probe behavior were similar to those reported
      previously for PPDPC in DPPC. In gel state DNPC [(T-T(m))<-10] the high values
      for excimer/monomer emission ratio (I(e)/I(m)) suggest enrichment of the probe in
      clusters. In this temperature range, excimer fluorescence for PPDPC (mole
      fraction X(PPDPC)=0.02) is described by two formation times up to (T-T(m))
      approximately -10, with a gradual disappearance of the fractional intensity
      (I(R1)) of the shorter formation time (tau(R1)) with increasing temperature up to
      (T-T(m)) approximately -10. This would be consistent with the initiation of the
      bilayer melting at the PPDPC clusters and the subsequent dispersion of the one
      population of PPDPC domains. A pronounced decrement in I(e) starts at (T-T(m))=
      10, continuing until T(m) is reached. No decrease was observed in fluorescence
      quantum yield in contrast to our previous study on DPPC/PPDPC large unilamellar
      vesicles (LUVs) [J. Phys. Chem., B 107 (2003) 1251], suggesting that a lack of
      proper hydrophobic mismatch may prevent the formation of the previously reported
      PPDPC superlattice. With further increase in temperature and starting at (T-T(m))
      approximately -1, I(e), tau(R2), and excimer decay times (tau(D)) reach plateaus
      while increment in trans-->gauche isomerization continues. This behavior is in
      keeping with an intermediate phase existing in the temperature range -1<(T
      T(m))<4 and transforming into the liquid disordered phase as a second order
      process, the latter being completed when (T-T(m))-->4 and corresponding to
      approximately 50% of the total transition enthalpy.

PMID- 15157625
TI  - Revisiting the pestilence of Helicobacter pylori: insights into geographical
      genomics and pathogen evolution.
AB  - Helicobacter pylori causes chronic gastritis and plays important roles in peptic
      ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT)
      lymphoma. It is believed that H. pylori infects over 50% of the worlds'
      population. However, only a small subset of infected people experience H. pylori
      associated illnesses. Associations with disease-specific factors remain
      enigmatic. The contribution of comparative genomics to our understanding of the
      genome organisation and diversity of H. pylori is exemplified herein. The
      discovery of the cag pathogenicity island has revolutionised our understanding of
      the molecular pathogenesis of gastroduodenal ulcers. Another type IV secretion
      system, the comB gene cluster, provides a novel transformation system.
      Identification of this cluster has boosted our perception of horizontal gene
      transfer and gene mosaicism in H. pylori as a result of natural competence.
      Recent discovery of a third type IV secretion system called tfs3 encoding cluster
      in the so called plasticity zone of the H. pylori has gained significant
      attention, although its role is not clear. Study of the evolution of
      polymorphisms and sequence variation in H. pylori populations on a global basis
      is contributing to understanding of the history of human population migration and
      co-evolution of this pathogen with its human host. Possible symbiotic
      relationships were debated since the discovery of this pathogen. The debate has
      been further intensified as recent studies have posed the intriguing possibility
      that H. pylori infection may be advantageous in some humans. This analogy is
      based on increased incidence of diseases like gastro-oesophageal reflux disease
      (GERD), Barrett's oesophagus and adenocarcinoma of the oesophagus following H.
      pylori eradication in some patients.

PMID- 15157626
TI  - Molecular players of homologous recombination in protozoan parasites:
      implications for generating antigenic variation.
AB  - A major impediment to vaccine development against infections caused by protozoan
      parasites such as Plasmodium falciparum and Trypanosoma is the extraordinary
      ability of these parasites to rapidly change their surface molecules, a
      phenomenon known as antigenic variation. A prominent determinant of antigenic
      variation in these organisms is associated with rearrangements of genes,
      especially those known as var in P. falciparum and vsg in Trypanosoma. However,
      mechanisms underlying generation of anitgenic diversities among these protozoan
      parasites are poorly understood. The hypothesis that links all the different
      sections in this review is that antigenic variations in the protozoan parasites
      is coupled with genetic rearrangements, which occur during the course of DNA
      break repair. Here, we provide comprehensive and up-to-date information on Rad51
      in these organisms, an eukaryotic homologue of bacterial RecA, and homologous
      recombination mechanisms. In trypanosomes both Rad51-dependent and -independent
      mechanisms have been suggested to play roles in antigenic variation. Finally, we
      speculate on how might similar DNA repair mechanisms contribute to genetic
      rearrangement associated with antigenic variation in the apicomplexan Plasmodium
      parasites, an immune evasion strategy.

PMID- 15157627
TI  - Evolution and conservation of microsatellite markers for Leishmania tropica.
AB  - Sixteen polymorphic microsatellite markers were developed for phylogenetic
      analysis of Leishmania tropica. The phylogenetic tests done demonstrated that
      they do provide a powerful tool for epidemiological studies. They were also
      tested for their ability to differentiate strains of other species of Leishmania,
      confirming that microsatellite markers developed for one leishmanial species
      cannot generally be used for other leishmanial species. In addition to length
      variation, a high degree of allelic heterozygosity was seen among the strains
      investigated, suggestive of sexual recombination within the species L. tropica.

PMID- 15157628
TI  - Variation in the structure of Toxoplasma gondii and the roles of selfing, drift,
      and epistatic selection in maintaining linkage disequilibria.
AB  - Previous studies of Toxoplasma gondii, based on samples dominated by clinical
      isolates, have concluded that its population structure is clonal, despite the
      sexual reproduction that occurs in cats. To determine whether this applies to non
      clinical isolates, we compared patterns of linkage disequilibrium (LD) among
      seven loci in samples of T. gondii from Brazil and the US. LD was detected in
      both locations, but it was substantially lower in Brazil. The lower LD in Brazil
      can be explained by a higher rate of sexual reproduction between different
      genotypes (outcrossing) because of a higher rate of transmission. The extent of
      LD between pairs of physically unlinked loci varied significantly in each
      location. Moreover, the magnitude of LD between corresponding locus pairs in
      Brazil and the US was correlated, despite minimal gene exchange between the
      continents (mean FST = 0.19). The heterogeneity among locus pairs and the
      correlation in LD between physically unlinked locus pairs from different
      continents suggests that locus-specific factors, such as epistatic selection are
      involved in maintaining LD in T. gondii. Possibly, the unique life cycle of T.
      gondii with its unpredictable transmission among diverse host species and
      distinct ecological habitats requires specific combinations of alleles from
      multiple loci. The usefulness of typing isolates based on physically unlinked
      loci is questioned not only by the geographic variation in the reproductive
      population structure, but mainly by the low overall predictability of the
      genotype of one locus based on the genotype in another (unlinked) locus. This
      predictability ranged between 23 and 45%, but was close to nil for a considerable
      fraction of locus pairs.

PMID- 15157630
TI  - Discrimination of all genotypes of Giardia duodenalis at the glutamate
      dehydrogenase locus using PCR-RFLP.
AB  - A PCR-RFLP genotyping tool was developed and used to characterise morphologically
      identical isolates of Giardia duodenalis from a variety of host species. Primers
      were designed to amplify a 432bp region of the glutamate dehydrogenase gene (gdh)
      from genetic Assemblages AI, AII, BIII, BIV, C, D and E of G. duodenalis. DNA
      extracted from cultured Giardia trophozoites, Giardia cysts purified from faeces
      and directly from whole faeces was amplified and sequenced at the gdh and 18SrDNA
      loci. The gdh sequences were identical with published gdh sequences for each
      assemblage with a few exceptions. However, in some cases genotyping results
      obtained using gdh differed from 18SrDNA genotyping results. From gdh sequence
      information a PCR-RFLP profile was identified for each of the genetic
      assemblages. PCR-RFLP is a reproducible, reliable and sensitive method for
      genotyping Giardia. Eight human, 12 cat, 9 dog and 16 cattle faecal isolates were
      genotyped using PCR-RFLP. This method allows G. duodenalis isolates from human
      beings, their companion animals and livestock to be genotyped directly from
      faeces, leading to valuable information about Giardia genotypes in population
      without the need for in vitro/in vivo amplification.

PMID- 15157629
TI  - High recombination rate in herpes simplex virus type 1 natural populations
      suggests significant co-infection.
AB  - Herpes simplex virus type 1 (HSV-1) is highly prevalent in all human populations
      and has been presumed to evolve in a clonal manner because of a lack of evidence
      for significant levels of co-infection. Different HSV-1 populations have distinct
      distributions of strains and the long timescale evident from HSV-1 population
      diversity has led to the suggestion that studies of virus variability may yield
      information about host population history. In this sequencing study of three
      segments of the HSV-1 genome in population samples from the UK and Korea,
      evidence of recombination was widespread both at the level of reassortment
      between widely separated loci and within shorter contiguous sequences and the
      estimated rate of recombination was comparable to that of mutation. Since
      recombination requires the coexistence of two viral genomes, these results
      suggest that co-infection by genetically distinct strains may be a more important
      aspect of HSV-1 epidemiology than previously realized. With its capacity to make
      new combinations of variants available for selection, substantial recombination
      requires a radically revised model for the rate and mode of evolution of the
      virus.

PMID- 15157631
TI  - Genetic variability of Brazilian Toxoplasma gondii strains detected by random
      amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and simple
      sequence repeat anchored-PCR (SSR-PCR).
AB  - The genetic variability of 19 Toxoplasma gondii strains isolated from humans and
      animals in Brazil was detected by both random amplified polymorphic DNA
      polymerase chain reaction (RAPD-PCR) and simple sequence repeat anchored-PCR (SSR
      PCR) for the first time. Two reference strains, RH (highly virulent) and ME49
      (avirulent), were submitted to both assays. Besnoitia sp., Plasmodium falciparum
      and Babesia bigemina were used as outgroups. RAPD-PCR and SSR-PCR profiles were
      used for building phenetic trees by unweighted pair group method with arithmetic
      averages (UPGMA). Phenograms built with TREECONW software showed great similarity
      in the topology of the trees. Both phenograms presented two major clusters that
      grouped T. gondii strains according to their murine virulence. The strains AS28,
      BV and N, which are highly virulent for BALB/c mice, were clustered with the
      reference strain RH, the highly virulent strain of T. gondii that has been most
      commonly studied. The group formed by the cystogenic strains showed that the
      strains which presented a level of virulence more similar to that of ME49 strain
      (avirulent) also presented a closer genetic relationship. Genetic variation
      within each lineage was significantly lower (P < 0.05) than that between the
      lineages. Regarding outgroups, Besnoitia sp. presented the closest relationship
      to T. gondii while P. falciparum was the most distant. The results presented here
      demonstrate that intraspecific genetic variability separates Brazilian T. gondii
      strains into two groups which correlate with murine virulence phenotype.

PMID- 15157632
TI  - Phylogeny of the Picornaviridae and differential evolutionary divergence of
      picornavirus proteins.
AB  - A rooted phylogenetic analysis of the viral family Picornaviridae identified
      several major clusters within this viral family. The genus Parechovirus,
      including Ljungan virus, was found to be basal to the family. Within the family,
      there were two major subgroups: (1) a cluster including viruses assigned to the
      genera Enterovirus and Rhinovirus; and (2) a cluster including Teschovirus,
      Cardiovirus, Erbovirus, Aphthovirus, and probably Kobuvirus. Within the former
      cluster, the genera Enterovirus and Rhinovirus were found not to be monophyletic.
      Principal components analysis was used to identify different patterns with regard
      to the relative sequence divergence of the 11 polyproteins encoded by the
      picornavirus genome. In comparisons of closely related pairs of viruses, the
      nonstructural proteins were generally more conserved than the capsid proteins 1B,
      1C, and 1D. This pattern is most likely explained by the predominance of host
      antibody-driven selection on the differentiation of closely related viral
      genomes. However, the same pattern was not seen in more distantly related pairs
      of viruses, which showed a number of distinct patterns with regard to the
      relative conservation of the 11 proteins.

PMID- 15157633
TI  - Spliced leader RNA gene promoter sequence heterogeneity in CL-Brener Trypanosoma
      cruzi reference strain.
AB  - Trypanosoma cruzi is divided into two phylogenetic lineages, T. cruzi I and T.
      cruzi II, which contain different spliced leader (SL) RNA gene promoter
      sequences: Class I SL gene promoter sequences are found in T. cruzi II, and Class
      II sequences in T. cruzi I. We analysed different SL RNA promoter sequences from
      CL-Brener reference strain, belonging to T. cruzi II lineage, and detected
      sequences that differed within the -80/+1 highly conserved region. Indeed, many
      of these divergent SL promoters present features of T. cruzi I promoters. Some of
      these sequences were grouped into the T. cruzi I sequences clade by Bayesian
      analysis. The results presented herein show that sequence heterogeneity in SL RNA
      gene promoter not only exists between T. cruzi strains but also within CL-Brener
      strain. These CL-Brener "T. cruzi I-like" sequences could be considered a
      molecular trace of a hybrid origin of the SL RNA gene and a new evidence for the
      presence of sequences of T. cruzi I origin into a T. cruzi II strain. The
      possible origins of these sequences are discussed.

PMID- 15157634
TI  - The best defence against bioweapons has already been invented by evolution.
AB  - Bioweapons are considered from the viewpoint of the mutual evolution of
      microbe/victim ecological systems. Cases considered include accidental,
      experimental, and real exploitation of bioweapons as well as other cases in the
      history of epidemics, and also experimental investigations. It is proposed here
      that speculations about bioweapon's very high mass annihilating ability are based
      on over-extrapolation from limited data selected from the ancient history of
      epidemics and on a false supposition that all people are susceptible to any
      bioweapon's infectious agent. The history of epidemics, clinical and genetic
      observations, data from experimental investigations, and results of accidental,
      experimental, and real exploitation of bioweapons do not confirm the mass
      annihilating capability of bioweapons. Many people possess constitutional
      (genetic) immunity presumably formed by natural selection over many human
      generations. This genetic protection exists in an individual prior to infection.
      The power of constitutional immunity played an important role during all human
      evolution. Its protective capability continues to defend humanity from mass
      annihilation by both epidemics and bioweapons. In this context of constitutional
      immunity for the majority of individuals, the main goal of modern medicine is to
      identify and defend the defenseless ones.

PMID- 15157635
TI  - Antituberculosis drugs and hepatotoxicity.

PMID- 15157637
TI  - Endometriosis: epidemiology and aetiological factors.
AB  - Estimates of the frequency of endometriosis vary widely. Based on the few
      reliable data, the prevalence of the condition can reasonably be assumed to be
      around 10%. Although no consistent information is available on the incidence of
      the disease, temporal trends suggest an increase among women of reproductive age.
      This could be explained-at least in part-by changing reproductive habits.
      Numerous epidemiological studies have indicated that nulliparous women and women
      reporting short and heavy menstrual cycles are at increased risk of developing
      endometriosis; data on other risk factors are less consistent. These
      epidemiological findings strongly support the menstrual reflux hypothesis.
      Additional evidence in favour of this theory includes the demonstration of viable
      endometrial cells in the menstrual effluent and peritoneal fluid, experimental
      implantation and growth of endometrium within the peritoneal cavity, observation
      of some degree of retrograde menstruation in most women undergoing laparoscopy
      during menses, and an association between obstructed menstrual outflow and
      endometriosis.

PMID- 15157638
TI  - Impact of endometriosis on women's health: comparative historical data show that
      the earlier the onset, the more severe the disease.
AB  - Looking at endometriosis from the bigger picture -- as a systemic endocrine,
      immunological, and gastrointestinal disease -- opens the door to broader
      treatments. The bigger-picture understanding of the disease also makes clear a
      variety of patterns of presenting symptoms, again clarifying the diagnosis. Data
      from over 7000 confirmed cases clearly show that delay in diagnosis (the average
      time to diagnosis is >9 years) is a major problem and that current treatments are
      far from satisfactory. In conclusion, the impact of endometriosis, a disease that
      already produces intense symptoms, is worsened by a current lack of understanding
      of the disease beyond its pelvic definition.

PMID- 15157639
TI  - Genetics of endometriosis: heritability and candidate genes.
AB  - Endometriosis is a complex gynecologic disorder that affects as many as 10-15% of
      premenopausal women. Epidemiologic studies have confirmed that this disease is a
      genetic disorder of polygenic/multifactorial inheritance. The disorder has long
      been recognized to show heritable tendencies with recurrence risks of 5-7% for
      first-degree relatives. The current investigational goal is to determine the
      number and location of causative genes, a process that has been made possible by
      recent advances in molecular technology. This chapter discusses heritability
      studies supporting polygenic/multifactorial inheritance, the scientific basis of
      genome-wide strategies for identifying causative genes and potential candidate
      genes.

PMID- 15157640
TI  - Pathogenesis of endometriosis.
AB  - Many women harbour spots of peritoneal endometriosis without having any symptoms;
      this is referred to as the phenomenon endometriosis. Some of these women go on to
      develop symptomatic endometriosis. Although we know the factors potentially
      involved in the aetiology and pathogenesis of endometriosis, the exact mechanism
      by which the phenomenon endometriosis develops into the disease endometriosis,
      with its associated signs and symptoms, remain obscure. The widely accepted
      theory is Sampson's transplantation theory. Recent findings indicate that certain
      properties of the endometrium, and the influence of the local environment, are
      crucial in the development of endometriosis. Early endometriosis lesion formation
      is described in detail, as this seems to be a key process in the development of
      peritoneal endometriosis.

PMID- 15157641
TI  - Immunology of endometriosis.
AB  - Endometriosis is a benign gynecologic disorder characterized by the ectopic
      growth of misplaced endometrial cells. A unifying hypothesis to explain
      endometriosis has not been elucidated as yet but numerous investigations have
      implicated disturbances in the immune response as fundamental to its etiology and
      pathogenesis. Clearly, the immune system is involved in endometriosis. It is not
      clear, however, whether and to what extent this involvement is a primary response
      leading to the initiation, promotion, and progression of the disease or a
      secondary response to the ectopic endometrial growth in an attempt to restore
      homeostasis. Thus, although numerous studies have shown alterations in cell
      mediated and humoral immunity in subjects with endometriosis, the importance of
      these changes remains obscure. This review considers the past two decades of
      investigation of immune function changes in women with endometriosis with the
      expectation that this information will ultimately provide the basis for
      developing new approaches to patient management.

PMID- 15157642
TI  - Steroid receptor action.
AB  - The ovarian hormones oestradiol and progesterone exert their actions on target
      cells predominantly through the binding and activation of the oestrogen receptor
      (ER) and progesterone receptor (PR), respectively. These receptors are members of
      the steroid/thyroid hormone superfamily of ligand-dependent transcription factors
      and bind to the control regions (promoters) of specific genes, where they recruit
      co-activators or co-repressors and the transcriptional machinery necessary to
      elicit gene expression. The ability of a nuclear receptor to modulate gene
      transcription is further dependent on its interaction with other transcription
      factors, which in turn can be regulated by either distinct or multiple
      cytoplasmic signalling pathways. This chapter summarises the extraordinary
      diversity of factors involved in determining the cellular response to a hormonal
      signal and emphasises the role of ER and PR in regulating ovarian and uterine
      functions.

PMID- 15157643
TI  - Diagnosis of endometriosis: pelvic endoscopy and imaging techniques.
AB  - Although laparoscopy is the gold standard for the diagnosis of endometriosis, the
      need for this invasive diagnostic tool is a major stumbling-block in both
      effective clinical management and for research into this common and debilitating
      disease. As visual inspection of the pelvis has also major limitations,
      particularly for the diagnosis of posterior pelvis, bowel and bladder
      endometriosis, it is not surprising that considerable efforts are being made to
      improve the diagnosis by imaging techniques. Peritoneal endometriosis and ovarian
      endometriomata are predominantly haemorrhagic lesions. During laparoscopy, these
      lesions are readily identified by the presence of old or recent bleeding. Both
      transvaginal sonography and magnetic resonance (MR) imaging have a low
      sensitivity for the diagnosis of peritoneal and ovarian implants and adhesions.
      Transvaginal sonography is useful in the diagnosis of ovarian endometriomata,
      providing the diameter is larger than 2 cm. As transvaginal sonography costs less
      than MR imaging, transvaginal sonography might be the preferred method of
      confirming a sizeable endometrioma. Posterior pelvis endometriosis is an
      infiltrating adenomyotic lesion with microendometriomata. High-resolution
      transvaginal ultrasonography, and in particular MR imaging, are increasingly used
      to diagnose the presence and extent of infiltrating lesions and the involvement
      of rectosigmoid and ureters.

PMID- 15157644
TI  - Serum and endometrial markers.
AB  - Endometriosis is a benign but aggressive disease. It occurs when shed endometrium
      from the female reproductive tract grows at a site outside the uterus. The
      physiological changes in endometriosis-abnormal tissue growth, invasion, and
      adhesion phenomena-are similar to those seen in tumorous tissues. Although the
      etiology of endometriosis is not well understood, the disease is widely accepted
      to result from the ectopic implantation of refluxed menstrual tissues. In
      addition, immunologic changes, genetic factors, and environmental factors might
      also affect a woman's susceptibility to develop endometriosis. Thus far,
      laparoscopic examination is required to confirm the presence of endometriosis;
      there is no reliable marker for its diagnosis. Many studies are therefore
      focusing on identifying markers for the diagnosis and follow-up of endometriosis.
      This chapter provides a systematic review of these studies, including recent
      findings from our group on the identification of molecules, in serum and/or
      endometrium, which are associated with the development of endometriosis at
      different stages. From this research, we hope to be able to suggest how to
      approach the potential markers. The identification of highly sensitive and
      specific markers of endometriosis should facilitate the development of accurate
      and non-invasive techniques for diagnosis and prognosis.

PMID- 15157645
TI  - New medical treatments for endometriosis.
AB  - The medical treatment of endometriosis has long centered upon producing a
      hypoestrogenic environment by producing pituitary suppression or a progestin
      dominant environment. However, as more is uncovered regarding the pathogenesis
      and pathophysiology of this disease, more targeted therapies can be developed.
      Current research has focused upon medications designed to attack specific aspects
      of the development and maintenance of endometriosis. These include progesterone
      receptor modulators, gonadotropin releasing hormone (GnRH) antagonists, aromatase
      inhibitors, tumor necrosis factor alpha (TNF-alpha) inhibitors, angiogenesis
      inhibitors, matrix metalloproteinase inhibitors, pentoxifylline (and other
      general immune modulators), and estrogen receptor beta agonists. It is hoped that
      this new wave of medications will improve the response to medical therapy for
      this disorder.

PMID- 15157646
TI  - Surgical management of endometriosis.
AB  - The efficacy of medical and surgical treatment of endometriosis-associated
      infertility and pelvic pain is a source of ongoing controversy. Complete
      resolution of endometriosis is not yet possible and current therapy has three
      main objectives: (1) to reduce pain; (2) to increase the possibility of
      pregnancy; and (3) to delay recurrence for as long as possible. It is possible
      that a consensus will never be reached on the optimal treatment of minimal and
      mild endometriosis. In case of moderate and severe endometriosis-associated
      infertility, the combined approach (operative laparoscopy with a gonadotropin
      releasing hormone (GnRH) agonist) should be considered as 'first-line' treatment.
      The mean pregnancy rate of 50% reported in the literature following surgery
      provides scientific proof that operative treatment should first be undertaken to
      give our patients the best chance of conceiving naturally. In case of
      rectovaginal adenomyotic nodules, surgery must be considered as first-line
      therapy, medical therapy being relatively in-efficacious.

PMID- 15157647
TI  - Endometriosis and the development of malignant tumours of the pelvis. A review of
      literature.
AB  - For several decades, endometriosis has been suspected of playing a role in the
      aetiology of ovarian cancer. The literature concerning a possible histogenesis of
      ovarian cancer from benign endometriosis is reviewed in this chapter.
      Epidemiological evidence from large-cohort studies confirms endometriosis as an
      independent risk factor for ovarian cancer. Further circumstantial evidence for
      this link was found in the common risk factors for ovarian cancer and
      endometriosis. These risk factors influence retrograde menstruation and
      endometriosis in the same positive or negative way. Based on data in the
      literature, the prevalence of endometriosis in epithelial ovarian cancer has been
      calculated to be 4.5, 1.4, 35.9, and 19.0% for serous, mucinous, clear-cell and
      endometrioid ovarian carcinoma, respectively. The risk of malignant
      transformation in ovarian endometriosis was calculated at 2.5% but this might be
      an underestimate. In addition, some authors described atypical endometriosis in a
      spatial and chronological association with ovarian cancer. Finally, molecular
      studies have detected common alterations in endometriosis and ovarian cancer.
      These data suggest that some tumours, especially endometrioid and clear-cell
      carcinomas, can arise from endometriosis. Moreover, endometriosis-associated
      ovarian cancer represents a distinct clinical entity, with a more favourable
      biological behaviour, given a lower stage distribution and better survival than
      non-endometriosis-associated ovarian cancer.

PMID- 15157649
TI  - Apoptosis may contribute to false-positive results in the in vitro micronucleus
      test performed in extreme osmolality, ionic strength and pH conditions.
AB  - Conditions in which clastogens produce positive responses have been increasingly
      challenged, and several situations have been described in which clastogenic
      responses would be considered not to be relevant. For example, extreme culture
      conditions lead to high variations of pH, osmolality or ionic strength. Apoptosis
      is induced in extreme culture conditions and contributes to false-positive
      results in the in vitro micronucleus test performed with CTLL-2 cells. These
      cells can enter apoptosis when exposed to apoptosis stimuli or after IL-2
      deprivation, whereas the CTLL-2 Bcl2 cell line is protected from apoptosis due to
      the over-expression of the apoptosis inhibitor Bcl2 in bcl2-transfected CTLL-2
      cells. The two cell lines were treated in extreme culture conditions of either pH
      or osmolality or were submitted to high ionic strength. The apoptosis level was
      measured in parallel with the in vitro micronucleus test using the annexin V-FITC
      method. Data obtained in the two cell lines suggested that apoptosis caused by
      extreme culture condition induces the formation of micronucleated cells, which
      leads to false-positive results in the in vitro micronucleus test.

PMID- 15157648
TI  - DNA lesions and cytogenetic changes induced by N-nitrosomorpholine in HepG2, V79
      and VH10 cells: the protective effects of Vitamins A, C and E.
AB  - INTRODUCTION: N-Nitrosomorpholine (NMOR), present in the workplace of tyre
      chemical factories, is a known hepatocarcinogen. This compound belongs to the
      group of N-nitrosamines, which are indirect-acting and require metabolic
      activation. However, the mechanism of its carcinogenic effect is not completely
      clear. AIMS: The objective of this study was (i) to compare the DNA-damaging and
      clastogenic effects of NMOR in three cell lines (HepG2, V79 and VH10) with
      different levels of metabolizing enzymes and (ii) to determine the protective
      effects of Vitamins A, C and E against deleterious effects of NMOR. METHODS: The
      exponentially growing cells were pre-treated with Vitamins A, C and E and treated
      with NMOR. Genotoxic effects of NMOR were evaluated by single-cell gel
      electrophoresis (SCGE, comet assay), while the chromosomal aberration assay was
      used for the study of clastogenic effects. KEY RESULTS: NMOR-induced a
      significant dose-dependent increase of DNA damage as analyzed by SCGE, but the
      extent of DNA migration in the electric field was unequal in the different cell
      lines. Although the results obtained by SCGE confirmed the genotoxicity of NMOR
      in all cell lines studied, the number of chromosomal aberrations was
      significantly increased only in HepG2 and V79 cells, while no changes were
      observed in VH10 cells. In HepG2 cells pre-treated with Vitamins A, C and E we
      found a significant decrease of the percentage of tail DNA induced by NMOR. The
      reduction of the clastogenic effects of NMOR was observed only after pretreatment
      with Vitamins A and E; Vitamin C did not alter the frequency of NMOR-induced
      chromosomal aberrations under the experimental conditions of this study.
      CONCLUSIONS: The fat-soluble Vitamins A and E, which are dietary constituents,
      reduce the harmful effects of N-nitrosomorpholine in human hepatoma cells HepG2,
      which are endowed with the maximal capacity for metabolic activation of several
      drugs.

PMID- 15157650
TI  - Mutations induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the
      lacZ and cII genes of Muta Mouse.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) found in chewing tobacco,
      snuff, cigarettes, and cigars is a tobacco-specific nitrosamine and classified as
      a possible human carcinogen (Class 2B) by the International Agency for Research
      on Cancer (IARC). NNK given intraperitoneally was seen to induce lung and liver
      adenomas. To evaluate the genotoxicity of NNK in vivo, NNK was intraperitoneally
      administered to Muta Mouse at two concentrations (125 and 250 mg/kg, once a week
      for 4 weeks) followed by the measurement of mutant frequencies in the lacZ and
      cII genes from lung and liver in the same mice. Characterization of the types of
      the mutation was determined by sequencing the cII genes from mutant plaques. The
      mutant frequencies in both target genes from both organs dose-dependently
      increased up to 10 times compared to those of the control group. For the types of
      mutations, the ratio of the G:C to A:T mutation in the total number of mutants
      was less than the ratio of A:T to T:A and A:T to C:G transversion, contrary to a
      previous report. The A:T to T:A transversion was the most highly induced mutation
      both in the lung and liver cII genes. The increasing rate of mutant frequencies
      in lung and liver over the vehicle control was 55 and 56 times, respectively,
      while the increasing rate of G:C to A:T transition was only 1.9 and 2.8 times,
      respectively. These observations show that NNK predominantly induces DNA adducts
      leading to A:T to T:A and/or A:T to C:G mutations in the transgene.

PMID- 15157651
TI  - Further characterization of loss of heterozygosity enhanced by p53 abrogation in
      human lymphoblastoid TK6 cells: disappearance of endpoint hotspots.
AB  - Loss of heterozygosity (LOH) is the predominant mechanism of spontaneous
      mutagenesis at the heterozygous thymindine kinase locus (tk) in TK6 cells. LOH
      events detected in spontaneous TK(-) mutants (110 clones from p53 wild-type cells
      TK6-20C and 117 clones from p53-abrogated cells TK6-E6) were analyzed using 13
      microsatellite markers spanning the whole of chromosome 17. Our analysis
      indicated an approximately 60-fold higher frequency of terminal deletions in p53
      abrogated cells TK6-E6 compared to p53 wild-type cells TK6-20C whereas
      frequencies of point mutations (non-LOH events), interstitial deletions, and
      crossing over events were found to increase only less than twofold by such p53
      abrogation. We then made use of an additional 17 microsatellite markers which
      provided an average map-interval of 1.6Mb to map various LOH endpoints on the
      45Mb portion of chromosome 17q corresponding to the maximum length of LOH tracts
      (i.e. from the distal marker D17S932 to the terminal end). There appeared to be
      four prominent peaks (I-IV) in the distribution of LOH endpoints/Mb of Tk6-20C
      cells that were not evident in p53-abrogated cells TK6-E6, where they appeared to
      be rather broadly distributed along the 15-20Mb length (D17S1807 to D17S1607)
      surrounding two of the peaks that we detected in TK6-20C cells (peaks II and
      III). We suggest that the chromosomal instability that is so evident in TK6-E6
      cells may be due to DNA double-strand break repair occurring through non
      homologous end-joining rather than allelic recombination.

PMID- 15157652
TI  - In vitro and in vivo chromosomal aberrations induced by megazol.
AB  - With the re-emergence of Human African Trypanosomiasis (HAT) on the one hand,
      which are increasingly resistant to current therapies, and the stage-dependent
      effectiveness or even the prohibitive cost of these therapies on the other hand,
      megazol, a 5-nitroimidazole thiadiazole highly active against various
      trypanosomal species, was assessed for its genotoxic potential. Very little
      information has become available until now. Two batches of megazol were provided
      by two different suppliers: Far-Manguinhos, a part of the Fiocruz foundation,
      under the Brazilian Minister of Health, and Delphia, a French company. These two
      batches, obtained by different synthetic routes, were studied by means of the in
      vitro micronucleus assay on L5178Y mouse lymphoma cells, in its microscale
      version. Both batches of magazol displayed a strong genotoxic activity in this
      screening assay. A second batch from Delphia was then investigated by use of two
      tests, i.e. the in vitro metaphase analysis with human lymphocytes and the in
      vivo micronucleus test in rat bone-marrow. Megazol was shown to be a potent
      inducer of in vitro and in vivo chromosomal aberrations. Although megazol is a
      potent trypanocidal agent and is orally bio-available, its toxicity dictates that
      it should not be developed further for the treatment of HAT and Chagas disease.
      All development work has therefore been discontinued.

PMID- 15157653
TI  - Genotoxicity of municipal landfill leachate on root tips of Vicia faba.
AB  - The genotoxicity of municipal landfill leachate was studied using the Vicia faba
      root-tip cytogenetic bioassay. Results show that landfill leachates collected in
      different seasons decreased the mitotic index (MI) and caused significant
      increases of micronucleus (MN) frequencies and anaphase aberration (AA)
      frequencies in a concentration-dependent manner (concentration expressed as
      'chemical oxygen demand' measured by the method of potassium dichromate oxidation
      (COD(Cr))). In addition, a seasonal difference in genotoxicity induced by
      leachate was observed. The results confirm that leachate is a genotoxic agent in
      plant cells and imply that exposure to leachate in the aquatic environment may
      pose a potential genotoxic risk to organisms. The results also show that the V.
      faba cytogenetic bioassay is efficient, simple and reproducible in genotoxicity
      studies of leachate, and that there is a correlation between the genotoxicity and
      the chemical measurement (COD(Cr)) of leachate.

PMID- 15157654
TI  - Smoking-related DNA adducts in anal epithelium.
AB  - Several studies have identified tobacco smoking as a risk factor for anal cancer
      in both women and men. Samples of anal epithelium from haemorrhoidectomy
      specimens from current smokers (n = 20) and age-matched life-long non-smokers (n
      = 16) were analysed for DNA adducts by the nuclease P(1) digestion enhancement
      procedure of 32P-postlabelling analysis. The study included 14 men and 22 women.
      Both qualitative and quantitative differences in the adduct profiles were
      observed between the smokers and non-smokers. The mean adduct level was
      significantly higher in the smokers than in the non-smokers (1.88 +/- 0.71)
      (S.D.) versus 1.36 +/- 0.60 adducts per 10(8) nucleotides, P = 0.02, two-tailed
      unpaired t-test with Welch's correction); furthermore, the adduct pattern seen in
      two-dimensional chromatograms revealed the smoking-related diagonal radioactive
      zone in 17/20 smokers, but not in any of the non-smokers (P < 0.00001, Fisher's
      exact test). These results indicate that components of tobacco smoke inflict
      genotoxic damage in the anal epithelium of smokers and provide a plausible
      mechanism for a causal association between smoking and anal cancer.

PMID- 15157655
TI  - Dihydroxyacetone, the active browning ingredient in sunless tanning lotions,
      induces DNA damage, cell-cycle block and apoptosis in cultured HaCaT
      keratinocytes.
AB  - Dihydroxyacetone (DHA), the active substance in sunless tanning lotions reacts
      with the amino groups of proteins to form a brown-colored complex. This non
      enzymatic glycation, known as the Maillard reaction, can also occur with free
      amino groups in DNA, raising the possibility that DHA may be genotoxic. To
      address this issue we investigated the effects of DHA on cell survival and
      proliferation of a human keratinocyte cell line, HaCaT. Dose- and time-dependent
      morphological changes, chromatin condensation, cytoplasmic budding and cell
      detachment were seen in cells treated with DHA. Several dead cells were observed
      after long-time (24 h) incubation with 25 mM DHA or more. Furthermore, an
      extensive decline in proliferation was observed 1 day after DHA exposure for 24
      h. When applied in different concentrations (5-50 mM) and for different time
      periods (1, 3 or 24 h) DHA caused a G(2)/M block after the cyclin B(1)
      restriction point. Exit from this cell-cycle block was associated with massive
      apoptosis, as revealed by a clonogenic assay, TUNEL staining and electron
      microscopy. Furthermore, DHA caused DNA damage as revealed by the alkaline comet
      assay. Preincubation with antioxidants prevented the formation of DNA strand
      breaks. The DHA toxicity may be caused by direct redox reactions, with formation
      of ROS as the crucial intermediates. The genotoxic capacity of DHA raises a
      question about the long-term clinical consequences of treatment of the skin with
      this commonly used compound.

PMID- 15157656
TI  - Clastogenic effect of ethanol in chronic and abstinent alcoholics.
AB  - Alcoholism is one of the main causes of damage for human health, being relevant
      to study the induction of chromosomal aberrations (CA) by ethanol, and to
      investigate the individual susceptibility to diseases caused by alcoholism. A
      cytogenetic study was performed in human peripheral blood lymphocytes of 29 heavy
      chronic alcoholics, 11 alcoholics in abstinence, and 10 controls. The values of
      the chromosomal aberrations, mitotic indexes (MI) and proliferation indexes (PI)
      were determined. A molecular cytogenetic study was also carried out using
      fluorescence in situ hybridization (FISH) method with DNA library probes for
      chromosomes 1, 3 and 6, in lymphocytes from chronic alcoholic individuals in
      comparison with a control group. The results showed that the CA frequencies for
      chronic alcoholics (5.15 CA/100 cells) and alcoholics in abstinence (3.87 CA/100
      cells) were higher than those obtained for control individuals (1.72 CA/100
      cells). The mean translocation frequencies (equivalent to the genome) were
      calculated for six chronic alcoholics (0.267 translocations/100 cells) and six
      alcoholics in abstinence (0.167 translocations/100 cells), whose values were
      significantly higher than those observed for six control individuals (0.067
      translocations/100 cells). The CA frequencies were not statistically different
      when smoker and non-smoker alcoholics were compared, indicating that although the
      smoking habit had significantly increased (four-fold) the CA frequency in healthy
      control individuals, a lack of interaction effect was observed within the group
      of alcoholics when smokers and non-smokers were compared. The CA frequencies
      presented by alcoholics in abstinence were similar to those obtained for chronic
      alcoholics. Therefore, chronic ethanol intoxication can lead to chromosome damage
      and disturbances in the metabolism of endogenous and exogenous compounds, which
      may persist for a long time, and constitute a relevant factor of risk for the
      development of neoplasias.

PMID- 15157657
TI  - 6-Dimethylaminopurine (6-DMAP), which is used to produce most cloned animals, is
      mutagenic in Salmonella typhimurium TA1535.
AB  - 6-Dimethylaminopurine (6-DMAP) and cycloheximide have recently been used for
      successful production of cloned mammals. We investigated whether 6-DMAP or
      cycloheximide are mutagenic agents in the Ames test. Whereas cycloheximide showed
      no differences compared to the negative control in any of the tester strains, 6
      DMAP was clearly mutagenic in Salmonella typhimurium strain TA1535. Here, we
      strongly propose that innocuous chemicals be used in the production of cloned
      animals.

PMID- 15157658
TI  - The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g.
      acute leukemia.
AB  - In the past decades, a lot of effort has been put in identifying the role of
      matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in
      angiogenesis, tumor growth and metastasis is degradation of extracellular matrix
      (ECM) and release and/or activation of growth factors through their degradative
      activity. The degradative activity finally results in cancer progression. MMP
      inhibitors (MMPIs) have already been designed and tested, based on the
      degradative role of MMPs in cancer progression. First clinical trials with MMPIs
      have been performed with disappointing results, showing that in order to use MMP
      inhibition the mechanisms underlying MMP-expression in cancer have to be further
      elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular
      level and discusses the role for MMPs and MMP-inhibition in cancer with special
      focus on acute leukemia.

PMID- 15157659
TI  - Experimental therapy of malignant mesothelioma: new perspectives from anti
      angiogenic treatments.
AB  - We reviewed the published literature of clinical studies in malignant
      mesothelioma (MM), including phase II as well as older single-agent and
      combination chemotherapy trials with more than 15 patients. While response rates
      exceeding 30% have been achieved with established cytotoxic drugs in MM therapy,
      novel chemotherapeutic agents and their combinations appear more promising. This
      applies especially to the anti-metabolites (i.e. pemetrexed) that produced
      response rates of up to 45% in combination with platinum compounds. Moreover,
      agents targeting novel proliferative and survival pathways in MM are developed to
      improve treatment outcomes. Here, we focused on the role of several angiogenic
      growth factors in MM biology and the data of MM-oriented studies on angiostatic
      agents tested in a phase I-II trial. It seems likely that no single treatment
      modality will be effective by itself. Studies that use combinations of the newer
      agents, including angiostatic drugs, with chemotherapy, should be conducted.

PMID- 15157661
TI  - Review of the prognostic factors in medulloblastoma of children and adults.
AB  - Medulloblastoma (MB) is rare in adults, accounting for 1% of all primary tumours
      of the central nervous system (CNS). Based on the assumption that the disease
      pattern in adults is similar to that in children, adults with medulloblastoma are
      treated using paediatric protocols. Thanks to progress made in recent years, long
      term survival is now possible, with overall ranging from 50 to 60% at 5 years and
      40 to 50% at 10 years. However, effective therapy may have devastating long-term
      side effects, including neuro-psychic and neuro-endocrine sequelae and cognitive
      dysfunction, especially in young adults. Great interest has been expressed in new
      biological and molecular prognostic factors, which, combined with clinical
      variables, may allow a more satisfactory stratification of patients.

PMID- 15157660
TI  - Enhancement of radiotherapy with DNA topoisomerase I-targeted drugs.
AB  - Since its discovery more than a century ago, ionizing radiation has become a
      mainstay therapy for patients suffering from cancers. Currently, radiotherapy
      provides cure or palliative care for approximately one half of the cancer
      population. The anticancer efficacy of radiotherapy is, however, largely limited
      by its lack of tumor specificity and, consequently, normal tissue toxicity. There
      is an urgent need to develop systemic adjuncts that can enhance the efficacy and
      the selectivity of radiotherapy toward tumor cells. DNA topoisomerase I (TOP1)
      targeted drugs such as camptothecin derivatives represent a novel class of
      chemotherapeutic agents that have recently been shown to be excellent radiation
      sensitizers. Combined modality therapy with TOP1-targeted drugs and radiotherapy
      represents a new promising cancer therapy. The mechanism of enhancement of
      radiotherapy by TOP1-targeted drugs is under intense investigation. Clinical
      trials using combinations of radiation and camptothecin derivatives are also
      currently ongoing in various solid tumors including brain, head and neck, and
      lung cancers. A better understanding of the radiosensitization (RS) mechanism of
      TOP1-targeted drugs is pivotal to their clinical application, as well as in
      guiding the development of better radiation sensitizers.

PMID- 15157662
TI  - The economics of the colony-stimulating factors in the prevention and treatment
      of febrile neutropenia.
AB  - Healthcare costs continue to rise with hospitalization representing the single
      largest component of direct medical costs associated with cancer care.
      Neutropenia and its complications including febrile neutropenia remain the major
      dose-limiting toxicity associated with systemic cancer chemotherapy. Febrile
      neutropenia often occurs early in the course of chemotherapy and is associated
      with substantial morbidity, mortality and cost. The colony-stimulating factors
      (CSFs) have been used effectively in a variety of clinical settings to prevent or
      treat febrile neutropenia and to assist patients receiving dose-intensive
      chemotherapy. A meta-analysis of the available randomized controlled trials
      (RCTs) has confirmed the efficacy of prophylactic CSFs. Economic models based on
      measures of resource utilization derived from RCTs have provided estimates of
      expected treatment costs along with febrile neutropenia risk threshold estimates
      for the cost saving use of the CSFs. Recent studies have demonstrated the
      potential value of targeting the CSFs toward patients at greatest risk based on
      accurate and valid predictive models.

PMID- 15157663
TI  - Cancer of pancreas.
AB  - Cancer of the pancreas is the tenth most frequent cancer in Europe, accounting
      for some 3% of cancer in both sex. Smoking has been clearly established as a
      major risk factor affecting the carcinogenesis of pancreatic carcinoma. Diet has
      also been associated with pancreatic cancer, although no conclusive data are yet
      available. Different genetic alterations have been observed in pancreatic
      neoplasms. Typical symptoms of pancreatic cancer are: jaundice, abdominal pain
      and weight loss. The prognosis of pancreatic carcinoma depends mainly on radical
      surgery and the presence of negative resection margins, as well as on the
      biological tumour stage, which also influences the treatment strategy. The
      treatment of pancreatic cancer is undertaken with two aims. Radical surgery is
      indicated for patients with early stage of disease, mainly stage I and partially
      II. In all other cases, the aim of treatment is the palliation of different very
      distressing symptoms related to this neoplasm.

PMID- 15157664
TI  - Histiocyte disorders.

PMID- 15157665
TI  - Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement.
AB  - The ubiquitous protein chaperone hsp90 has been shown to regulate more than 100
      proteins involved in cellular signalling. These proteins are called 'client
      proteins' for hsp90, and a multiprotein hsp90/hsp70-based chaperone machinery
      forms client protein.hsp90 heterocomplexes in the cytoplasm and the nucleus. In
      the case of signalling proteins that act as transcription factors, the client
      protein.hsp90 complexes also contain one of several TPR domain immunophilins or
      immunophilin homologs that bind to a TPR domain binding site on hsp90. Using
      several intracellular receptors and the tumor suppressor p53 as examples, we
      review evidence that dynamic assembly of heterocomplexes with hsp90 is required
      for rapid movement through the cytoplasm to the nucleus along microtubular
      tracks. The role of the immunophilin in this system is to connect the client
      protein.hsp90 complex to cytoplasmic dynein, the motor protein for retrograde
      movement toward the nucleus. Upon arrival at the nuclear pores, the
      receptor.hsp90.immunophilin complexes are transferred to the nuclear interior by
      importin-dependent facilitated diffusion. The unliganded receptors then
      distribute within the nucleus to diffuse patches from which they proceed in a
      ligand-dependent manner to discrete nuclear foci where chromatin binding occurs.
      We review evidence that dynamic assembly of heterocomplexes with hsp90 is
      required for movement to these foci and for the dynamic exchange of transcription
      factors between chromatin and the nucleoplasm.

PMID- 15157666
TI  - TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene
      expression.
AB  - The balance between production and degradation of type I collagen plays a
      critical role in the development and maintenance of organ and tissue integrity.
      It also represents the most crucial element governing the process of tissue
      repair. The synthesis of type I collagen gene is highly regulated by different
      cytokines at the transcriptional level. Especially, transforming growth factor
      beta (TGF-beta), a key player in the physiopathology of tissue repair, enhances
      type I collagen gene expression. In contrast, tumor necrosis factor alpha (TNF
      alpha), whose matrix-remodelling function is opposite to that of TGF-beta,
      reduces type I collagen gene expression. This review focuses on transcriptional
      regulation of type I collagen by TGF-beta and TNF-alpha and on the molecular
      mechanisms that control the antagonistic activity of TNF-alpha against TGF-beta
      driven type I collagen gene expression.

PMID- 15157667
TI  - Antigen receptor-mediated signaling pathways in transitional immature B cells.
AB  - Engagement of antigen receptors on immature B cells induces apoptosis, while at
      the mature stage, it stimulates cell activation and proliferation. The difference
      in B cell receptor (BCR)-mediated signaling pathways regulating death or survival
      of B cells is not fully understood. We aimed to characterize the pathway leading
      to BCR-driven apoptosis. Transitional immature B cells were obtained from the
      spleen of sublethally irradiated and auto-reconstituted mice. We have detected a
      short-lived BCR-driven activation of mitogen-activated protein kinases (ERK1/2
      and p38 MAPK) and Akt/PKB in transitional immature B cells that correlated with
      the lack of c-Fos expression, reduced phosphorylation of Akt substrates and a
      susceptibility for apoptosis. Simultaneous signaling through BCR and CD40
      protected immature B cells from apoptosis, however, without inducing Bcl-2
      expression. The BCR-induced apoptosis of immature B cells is a result of the
      collapse of mitochondrial membrane potential and the subsequent activation of
      caspase-3.

PMID- 15157668
TI  - Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase
      Ialpha by a novel mechanism.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) plays an important role during actin
      polymerization and is produced by the type I phosphatidylinositol 4-phosphate 5
      kinases (PIP5KI), which are activated by phosphatidic acid (PA). As
      diacylglycerol kinases (DGKs) generate PA by phosphorylating diacylglycerol
      (DAG), we investigated whether DGKs were involved in controlling PIP2 levels by
      regulating PIP5KI activity. Here we show that expression of DGKzeta significantly
      enhances PIP5KIalpha activity in thrombin-stimulated HEK293 cells, and DGK
      activity is required for this stimulation. We also observed that DGKzeta co
      immunoprecipitated and co-localized with PIP5KIalpha, suggesting that they reside
      in a regulated signaling complex. To explore the role of DGKzeta in actin
      polymerization, we examined the subcellular distribution of DGKzeta, PIP5KIalpha
      and actin, and found that these proteins co-localized with actin in lamellipodial
      protrusions. Supporting that PIP5KIalpha regulation occurs at the sites of actin
      polymerization, we found that PIP2 also accumulated in the actin-rich regions of
      lamellipodia. Significantly, in wounding assays, DGKzeta, PIP5KIalpha and PIP2
      accumulated at the leading edge of migrating A172 cells, where massive actin
      polymerization is known to occur. Combined, these data support a novel function
      for DGKzeta: by generating PA, it stimulates PIP5KIalpha activity to increase
      local PIP2, which regulates actin polymerization.

PMID- 15157669
TI  - Role of the Sec14-like domain of Dbl family exchange factors in the regulation of
      Rho family GTPases in different subcellular sites.
AB  - Mechanisms underlying subcellular region-specific regulation of Rho family
      GTPases through Dbl family guanine nucleotide exchange factors (GEFs) remain
      totally unknown. Here we show that the Sec14-like domain, which lies in the N
      terminus of the Dbl family GEFs Dbl and Ost, directs the subcellular localization
      of these GEFs and also their substrate Cdc42. When coexpressed with Cdc42 in
      human adenocarcinoma HeLa cells, Dbl-I and Ost-I, which lack the Sec14-like
      domain, translocated Cdc42 to the plasma membrane, where Dbl-I or Ost-I was
      colocalized. In marked contrast, Dbl-II and Ost-II, which contain the Sec14-like
      domain, were colocalized with Cdc42 in endomembrane compartments. Furthermore,
      ruffle membrane formation upon epidermal growth factor treatment was mediated by
      Dbl-I or Ost-I, but neither Dbl-II nor Ost-II, supporting a notion that GEFs with
      or without the Sec14-like domain are linked to different upstream signals. By
      employing a novel method to detect the active GTP-bound form of Cdc42 in situ, we
      demonstrate that Dbl-I and Ost-I, but neither Dbl-II nor Ost-II, indeed activate
      colocalized Cdc42.

PMID- 15157670
TI  - Changes in intracellular cAMP reported by a Redistribution assay using a cAMP
      dependent protein kinase-green fluorescent protein chimera.
AB  - We report on a novel method to monitor changes in intracellular cAMP
      concentration ([cAMP]i) within intact living cells using a chimeric fusion of the
      catalytic subunit of cAMP-dependent protein kinase to green fluorescent protein
      (PKAcat-GFP). In stably transfected unstimulated fibroblasts, fusion protein
      fluorescence is highly concentrated in aggregates throughout the cytoplasm and
      absent in the nucleus. Elevation of [cAMP]i disperses GFP fluorescence from the
      cytoplasmic aggregates within minutes. Spot-photobleach measurements show that
      the rate of exchange of GFP-labeled catalytic subunits at these aggregates
      increases in proportion to [cAMP]i. For any given stimulus, the response curve
      for dispersal of GFP fluorescence from aggregates agrees closely with the
      increase in total [cAMP]i as measured by standard in vitro methods (SPA). The
      redistribution of fluorescence is completely reversible: reduction of [cAMP]i
      results in return of fluorescence to the cytoplasmic aggregates. Consistent
      behaviour of PKAcat-GFP is seen in different cell backgrounds. We demonstrate
      that PKA Redistribution assays are suitable for measurement of changes in [cAMP]i
      brought about by both Gs- and Gi-protein-coupled receptor stimulation as well as
      by inhibition of cAMP phosphodiesterases.

PMID- 15157671
TI  - Inhibition of phospholipase C-epsilon by Gi-coupled receptors.
AB  - We recently reported that several Gs-coupled receptors stimulate phospholipase C
      (PLC)-epsilon via increased formation of cyclic AMP and subsequent activation of
      the small GTPase Rap2B by the cyclic AMP-activated exchange factor Epac1. Here we
      show by studies in HEK-293 and N1E-115 neuroblastoma cells that this stimulation
      induced by Gs-coupled receptors or the direct adenylyl cyclase activator,
      forskolin, is potently inhibited by Gi-coupled receptors, known to inhibit cyclic
      AMP formation. PLC inhibition by the overexpressed M2 muscarinic receptor and the
      endogenously expressed sphingosine-1-phosphate and delta-opioid receptors was
      fully pertussis toxin-sensitive and accompanied by a reduction in Rap2B
      activation induced by Gs-coupled receptors. In contrast, Rap2B activation and PLC
      stimulation induced by membrane-permeable cyclic AMP analogues, including an Epac
      specific activator, or PLC stimulation caused by constitutively active Rap2B were
      not affected by the Gi-coupled receptors. In summary, our data indicate that Gi
      coupled receptors can inhibit PLC-epsilon, most likely by suppressing formation
      of cyclic AMP required for Epac-mediated Rap2B activation.

PMID- 15157672
TI  - A novel receptor function for the heat shock protein Grp78: silencing of Grp78
      gene expression attenuates alpha2M*-induced signalling.
AB  - The activated proteinase inhibitor alpha2-macroglobulin (alpha2M*) binds to two
      receptors, the low density lipoprotein receptor-related protein (LRP-1) and the
      alpha2M* signalling receptor (alpha2MSR). Silencing LRP-1 gene expression in
      macrophages by RNA interference does not block alpha2M* activation of signalling
      cascades. We now demonstrate that transfection of macrophages with a double
      stranded RNA homologous in sequence to the Grp78 gene markedly decreased
      induction of inositol 1,4,5-trisphosphate (IP3) and subsequent IP3-dependent
      elevation of [Ca2+]i induced by alpha2M*. Concomitantly, alpha2M*-induced
      increase in [3H]thymidine uptake was abolished in these transfected cells.
      Insulin treatment significantly upregulates alpha2MSR and it also caused a marked
      increase in Grp78 expression which could be blocked by RNA interference. alpha2M*
      treatment of cells activates the Ras- and PI 3-kinase-dependent signalling
      pathways. Suppressing Grp78 expression leads to the loss of these activation
      events in transfected macrophages. We thus conclude that Grp78 is the alpha2M*
      signalling receptor.

PMID- 15157673
TI  - Fine-tuning of helper T cell activation and apoptosis by antigen-presenting
      cells.
AB  - The role of antigen-presenting cells (APC) in regulating helper T cell responses
      and activation-induced cell death (AICD) was investigated in vitro. T cell
      activation was monitored by measuring the early rise of intracellular free
      calcium [Ca+]ic, mRNA and cell surface expression of activation and apoptotic
      molecules, the production of cytokines and the activation of transcription
      factors. Our results demonstrate that the unique characteristics of a given APC
      can modify the threshold, kinetics and magnitude of the T cell response. The
      rapid and sustained rise of intracellular free calcium correlated well with the
      extent of cytokine production and the expression of activation molecules. Fas
      dependent AICD could be induced by the most potent antigen-presenting cell (2PK3)
      only. Our results demonstrate that the response and fate of effector/memory CD4+
      helper T lymphocytes is highly dependent on the individual properties of the APC
      they encounter.

PMID- 15157674
TI  - Regulation of protein kinase B/Akt activity and Ser473 phosphorylation by protein
      kinase Calpha in endothelial cells.
AB  - Protein kinase Balpha (PKBalpha/Akt-1) is a key mediator of multiple signaling
      pathways involved in angiogenesis, cell proliferation and apoptosis among others.
      The unphosphorylated form of Akt-1 is virtually inactive and its full activation
      requires two phosphatidylinositol-3,4,5-triphosphate-dependent phosphorylation
      events, Thr308 by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser473 by an
      undefined kinase that has been termed PDK2. Recent studies have suggested that
      the Ser473 kinase is a plasma membrane raft-associated kinase. In this study we
      show that protein kinase Calpha (PKCalpha) translocates to the membrane rafts in
      response to insulin growth factor-1 (IGF-1) stimulation. Overexpression of
      PKCalpha increases Ser473 phosphorylation and Akt-1 activity, while inhibition of
      its activity or expression decreases IGF-1-dependent activation of Akt-1.
      Furthermore, in vitro, in the presence of phospholipids and calcium, PKCalpha
      directly phosphorylates Akt-1 at the Ser473 site. We conclude, therefore, that
      PKCalpha regulates Akt-1 activity via Ser473 phosphorylation and may function as
      PDK2 in endothelial cells.

PMID- 15157675
TI  - Novel effect of Y-24180, a presumed specific platelet activation factor receptor
      antagonist, on Ca2+ levels and growth of human prostate cancer cells.
AB  - In human prostate cancer PC3 cells, the effect of Y-24180, a presumed specific
      platelet activation factor (PAF) receptor antagonist, on intracellular Ca2+
      concentration ([Ca2+]i) was measured by using fura-2 as a Ca2+-sensitive
      fluorescent probe. Y-24180 (1-10 microM) caused a rapid and sustained [Ca2+]i
      rise in a concentration-dependent manner. The [Ca2+]i rise was prevented by 40%
      by removal of extracellular Ca2+, but was not changed by dihydropyridines,
      verapamil and diltiazem. In Ca2+-free medium, thapsigargin, an inhibitor of the
      endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which
      the increasing effect of 10 microM Y-24180 on [Ca2+]i was reduced by 67%;
      conversely, depletion of Ca2+ stores with 10 microM Y-24180 abolished
      thapsigargin-induced [Ca2+]i rise. U73122, an inhibitor of phospholipase C,
      inhibited ATP-, but not Y-24180-induced [Ca2+]i rise. Activation of protein
      kinase C with phorbol-12-myristate-13-acetate (PMA) enhanced Y-24180-induced
      [Ca2+]i rise by 70%. Overnight treatment with 0.1-10 microM Y-24180 inhibited
      cell proliferation in a concentration-dependent manner. Collectively, these
      results suggest that Y-24180 acts as a potent and cytotoxic Ca2+ mobilizer in
      prostate cancer cells, by stimulating both extracellular Ca2+ influx and
      intracellular Ca2+ release. Since alterations in Ca2+ movement may interfere with
      many cellular signalling processes unrelated to modulation of PAF receptors,
      caution must be applied in using this reagent as a selective PAF receptor
      antagonist.

PMID- 15157676
TI  - Ceramide-induced enhancement of secretory phospholipase A2 expression via
      generation of reactive oxygen species in tumor necrosis factor-alpha-stimulated
      mesangial cells.
AB  - Since prostanoids such as prostaglandin E2 play a pivotal role in modulating
      renal function, we investigated the involvement of ceramide in expression of
      secretory phospholipase A2 (sPLA2) and cyclooxygenase-2 (COX-2) in tumor necrosis
      factor-alpha (TNF-alpha)-stimulated mesangial cells. TNF-alpha stimulation
      increased ceramide generation in parallel with a decrease in sphingomyelin.
      Pretreatment with exogenous sphingomyelinase (SMase) dose-dependently enhanced
      TNF-alpha-stimulated increases in COX-2 protein and sPLA) activity. SMase also
      augmented TNF-alpha-mediated nuclear factor kappaB (NF-kappaB) activation. N
      acetylcysteine (NAC), an antioxidant, completely inhibited the SMase-induced
      increase in sPLA2 activity, whereas NAC inhibited partially the activity
      stimulated with TNF-alpha alone. Under the conditions, NAC completely inhibited
      reactive oxygen species (ROS) production induced by SMase followed by TNF-alpha.
      These results suggest that ceramide elicits up-regulation of NF-kappaB through
      ROS production, which, in turn, leads to stimulation of COX-2 and sPLA2
      expression. Therefore, ceramide may be implicated in the pathogenesis of renal
      abnormalities.

PMID- 15157677
TI  - Acupuncture: who is missing the point?

PMID- 15157678
TI  - Process and change in cognitive behaviour therapy for chronic pain.

PMID- 15157679
TI  - Potent opioids for chronic musculoskeletal pain: flying blind?

PMID- 15157680
TI  - A new view on how AMPA receptors and their interacting proteins mediate
      neuropathic pain.

PMID- 15157681
TI  - Decrease in non-selective, non-sustained attention induced by a chronic visceral
      inflammatory state as a new pain evaluation in rats.
AB  - The aim of this study was to develop a new behavioral pain test based on the
      evaluation of cognitive capacity impairments in rats with colitis and to
      determine the impact of different acute analgesic treatments. Colitis was induced
      in rats by an enema containing 2,4,6-trinitrobenzen sulfonic acid. Visual non
      selective, non-sustained attentional level was assessed by a new behavioral
      testing procedure. Animals were familiarized on three consecutive days with an
      open field containing four small, similar, familiar objects. On the day of
      testing, one of the objects was randomly replaced by a new one. Attentional level
      was determined by the ability of the rat to perceive this small modification to
      its familiar environment. The effect of morphine, acetaminophen, aspirin or
      ibuprofen treatment was assessed on testing day and compared with that observed
      during a Von Frey test to assess referred tactile hypersensitivity of the skin of
      the lower back. Rats with colitis had decreased attentional level but no change
      in their locomotor activity, interest in the environment or memory encoding.
      Morphine (1 mg/kg, s.c. and 10 microg/rat, i.t.) and acetaminophen (200 mg/kg,
      p.o.) had a beneficial effect on attentional level and on referred tactile
      hypersensitivity. Testing for the latter showed that aspirin and ibuprofen (400
      mg/kg, p.o.) were ineffective. The decrease in visual non-selective, non
      sustained attention induced by chronic inflammatory painful state can be relieved
      by effective analgesic treatments. This finding could lead to the development of
      a new behavioral test to assess spontaneous pain in chronic painful subjects.

PMID- 15157682
TI  - Associations between pain and neuromuscular activity in the human jaw and neck
      muscles.
AB  - The aim of this study was to test the effects of glutamate-evoked jaw or neck
      muscle pain on electromyographic (EMG) activity of jaw and neck muscles in
      humans. EMG recordings were made from left (MAL) and right (MAR) masseter
      muscles, and right sternocleidomastoid (SCM) and splenius (SP) muscles in three
      different head positions (head rest, head back, head right) or during maximal jaw
      clenching in 19 men. Glutamate (1 M) or isotonic saline was injected into MAR or
      SP, and induced pain was recorded on visual analogue scales. EMG activity in MAL
      and MAR was increased in the head back position compared to head rest and head
      right positions, whereas EMG activity in SCM and SP was progressively increased
      as the head was moved from rest position to head back to head right positions.
      Glutamate-evoked MAR pain was associated with increases in EMG activity in MAR,
      SCM and SP at rest but not in the head back or head right positions. Glutamate
      evoked SP pain was associated with an increase in SP EMG activity at rest and a
      decrease in SCM EMG activity in the head right position. Decreases in jaw clench
      related EMG activity were observed in MAL, MAR and SCM muscles only during
      glutamate-evoked MAR pain. Isotonic saline injections induced no pain or EMG
      changes. In conclusion, experimental neck pain is not associated with tonic
      increases in jaw EMG activity although jaw muscle pain can be linked to increases
      in neck EMG activity with the head and jaw at rest.

PMID- 15157683
TI  - Relationship between changes in coping and treatment outcome in patients with
      Fibromyalgia Syndrome.
AB  - The present study utilized a sample of 198 individuals with Fibromyalgia Syndrome
      (FMS) to examine the association between treatment process variables (beliefs,
      coping strategies) and treatment outcomes (pain severity, activity level,
      emotional distress and life interference) related to a 4-week multidisciplinary
      fibromyalgia treatment program. Multiple regression analyses were utilized to
      evaluate these relationships pretreatment to posttreatment as well as from
      pretreatment to 3- and 6-month follow-ups. The results indicated that outcomes
      were most closely related to: (1) an increased sense of control over pain, (2) a
      belief that one is not necessarily disabled by FM, (3) a belief that pain is not
      necessarily a sign of damage, (4) decreased guarding, (5) increased use of
      exercise, (6) seeking support from others, (7) activity pacing and (8) use of
      coping self-statements. These findings are consistent with a cognitive
      behavioural model of fibromyalgia, and suggest targets for therapeutic change.

PMID- 15157684
TI  - Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective
      study.
AB  - Intrathecal (IT) opioid therapy is a treatment alternative for patients with
      severe chronic non-malignant pain. Several uncontrolled retrospective and
      prospective outcome studies have suggested a benefit in chronic non-malignant
      pain patients, but uncertainties about patient selection in these studies weaken
      the results. This study evaluated long-term outcome of IT opioid therapy in
      chronic non-malignant pain prospectively, and included two comparative groups to
      improve understanding of selection criteria and relative severity of intrathecal
      pump recipients (PRs). The study subjects included 38 PRs while the comparative
      groups included 31 intrathecal candidates who either had an unsuccessful trial,
      or declined the IT therapy, and another group of 41 newly referred patients. The
      following data were analyzed at study entry, and at 6 monthly intervals for a 3
      year period: Symptom Check List 90 (SLC-90), SF-36 Health survey, Beck Depression
      Inventory, McGill Pain Questionnaire (short form), Oswestry Disability Index,
      Pain Drawings and Pain rating on visual analogue scale. Data analysis suggests
      the study group of PRs had improvements in pain, mood, and function from baseline
      to 36 months. These same parameters improved among new referrals (less severe
      patients receiving conservative pain management) while non-recipients
      significantly worsened. Although PRs improved, they were still worse off at 36
      months than new referrals were at baseline. The study showed that when patients
      with extremely severe pain problems are selected as pump candidates, they will
      likely improve with the therapy, but their overall severity of pain and symptoms
      still remains high.

PMID- 15157685
TI  - A double-blind placebo-controlled comparison of tramadol/acetaminophen and
      tramadol in patients with postoperative dental pain.
AB  - The objective of this study was to compare the analgesic efficacy of
      tramadol/acetaminophen (APAP) (total dose 75 mg/650 mg) and tramadol (total dose
      100 mg) for the control of pain after oral surgery. A total of 456 patients with
      moderate-to-severe pain within 5 h after extraction of two or more third molars
      were randomized to receive two identical encapsulated tablets containing
      tramadol/APAP 37.5 mg/325 mg, tramadol 50 mg, or placebo. Tramadol/APAP was
      superior to tramadol (P < 0.001) or placebo (P < 0.001) on all efficacy measures:
      total pain relief (PAR) over 6 h (7.4, 2.5, and 1.5, respectively, on a scale of
      0-24); sum of pain intensity differences (PIDs) (3.1, 0.6, and 0.1, respectively,
      on a scale of -6 to 18); and sum of PAR and PID (10.5, 3.1, and 1.6,
      respectively, on a scale of -6 to 42). Median times to onset of perceptible and
      meaningful PAR were 37.6 and 126.5 min, respectively, for the tramadol/APAP group
      (P < 0.001) for each, compared with tramadol and placebo arms). The most common
      adverse events with active treatment were nausea, dizziness, and vomiting; these
      events occurred more frequently in the tramadol group than in the tramadol/APAP
      group. This study established the superiority of tramadol/APAP 75 mg/650 mg over
      tramadol 100 mg in the treatment of acute pain following oral surgery.

PMID- 15157686
TI  - Spousal congruence on disability, pain, and spouse responses to pain.
AB  - We examined congruence between chronic pain patients and their spouses on their
      reports of patient pain severity, patient disability, and spouse responses to
      pain. Patients reported that they were more physically and psychosocially
      disabled than their spouses reported them to be. However, spouses reported that
      the patients' pain was more severe than patients reported. Depressive disorders
      in the patient and gender interacted with patient-spouse ratings. For physical
      and psychosocial disability, depressed patient couples reported significantly
      larger differences in disability ratings than non-depressed patient couples. In
      addition, female patients' disability was rated as more severe by the female
      patients than by their husbands. Male patient couples did not report differences
      on physical disability. Findings relating to other forms of disability and to
      spouse responses are also described. The results are discussed in the context of
      an interpersonal perspective of chronic pain and have implications for the
      assessment of pain and disability.

PMID- 15157687
TI  - Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking
      induced by chronic inflammatory pain.
AB  - Previous studies from our laboratory have demonstrated that both chronic
      inflammatory pain, induced by intraplantar injection of complete Freund's
      adjuvant (CFA), and prolonged (48 h) stimulation of mu-opioid receptors (muOR) by
      systemic administration of a variety of selective agonists, resulted in enhanced
      plasma membrane targeting of delta-opioid receptors (deltaOR) in neurons of the
      dorsal spinal cord. To determine whether deltaOR trafficking induced by chronic
      inflammation was dependent on the activation of muOR, we investigated by
      immunogold cytochemistry the effects of intraplantar CFA injection on the plasma
      membrane density of deltaOR in muOR knockout (KO) mice. In untreated wild-type
      (WT) mice, only a small proportion of deltaOR was associated with neuronal plasma
      membranes in the dorsal horn of the spinal cord. The CFA-induced inflammation
      produced a significantly higher ratio of plasma membrane to intracellular
      receptors, as well as a 75% increase in the membrane density of immunoreactive
      deltaOR, in dendrites of the ipsilateral dorsal horn as compared to untreated
      mice. This increase in the membrane density of deltaOR was likely due to a
      recruitment of receptors from intracellular stores since no difference in the
      overall deltaOR immunolabeling density was evident between CFA-treated and
      untreated mice. Most importantly, the CFA-induced changes in deltaOR plasma
      membrane insertion seen in WT animals were not present in the spinal cord of muOR
      KO mice. These results demonstrate that the integrity of muOR is necessary for
      CFA-induced changes in deltaOR trafficking to occur and suggest that these
      changes could be elicited by stimulation of muOR by endogenous opioids released
      in response to chronic inflammatory pain.

PMID- 15157688
TI  - Modulation of morphine analgesia by site-specific N-methyl-D-aspartate receptor
      antagonists: dependence on sex, site of antagonism, morphine dose, and time.
AB  - Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors can modulate
      morphine analgesia in experimental animals and humans. However, this literature
      is highly inconsistent, with NMDA receptor antagonists variously shown to
      potentiate, attenuate or produce no effect on morphine analgesic magnitude. A
      number of factors influencing this modulation have been proposed, but no one has
      examined such factors simultaneously, and all existing studies in mice were
      conducted exclusively in male subjects. Thus, the influence of systemic
      administration of site-specific NMDA receptor antagonists-including
      dextromethorphan, dextrorphan, MK-801, LY235959, L-701,324, and Ro 25-6981-on
      morphine analgesia (15-45 mg/kg; 15, 30 and 60 min post-injection) was studied in
      male and female mice using the 49 degrees C tail-withdrawal test. We found that
      oral and intraperitoneal dextromethorphan, a low-affinity non-competitive
      antagonist, dose-dependently potentiated low-dose morphine analgesia but
      attenuated high-dose morphine analgesia. Dextrorphan and MK-801 were found to
      potentiate low- but not high-dose morphine analgesia. The competitive glutamate
      site antagonist, LY235959, and glycine-site antagonist, L-701,324, potentiated
      morphine analgesia at all doses. In contrast, the polyamine (NR2B) site
      antagonist, Ro 25-6981, attenuated morphine analgesia at all doses. Strikingly,
      the non-competitive antagonists produced no modulation of morphine analgesia
      whatsoever in female mice, whereas no sex differences were observed using
      competitive or NR2B antagonists. These findings indicate that NMDA modulation of
      morphine analgesia is critically influenced by sex, site of antagonism, morphine
      dose and time after injection. Our data suggest that NMDA antagonism via
      competitive or glycine site antagonism might result in more reliable clinical
      effects on morphine analgesia in both sexes.

PMID- 15157689
TI  - Effects of TRPV1 receptor antagonists on stimulated iCGRP release from isolated
      skin of rats and TRPV1 mutant mice.
AB  - Capsaicin antagonists including ruthenium red, capsazepine and iodo
      resiniferatoxin (I-RTX) have recently been shown to inhibit the activation by
      noxious heat of the capsaicin receptor (TRPV1) expressed in non-neuronal host
      cells, and natively, in cultured dorsal root ganglion cells. Noxious heat has
      been shown to release immunoreactive calcitonin gene-related peptide (iCGRP) from
      the isolated rat skin. In this model, ruthenium red, I-RTX as well as capsazepine
      10 microM caused no alteration in iCGRP release at 32 degrees C by themselves
      whereas capsazepine 100 microM doubled it reversibly. In wild-type mice 100
      microM capsazepine also stimulated iCGRP release while it was without effect in
      TRPV1 knockout littermates. In the rat skin, both ruthenium red and capsazepine
      (10/100 microM) reduced and abolished, respectively, capsaicin-induced iCGRP
      release while I-RTX (1/10 microM) was ineffective. Only ruthenium red 100 microM
      showed an unspecific effect inhibiting iCGRP release induced by KCl. Ruthenium
      red and capsazepine (10/100 microM) caused no significant alteration of iCGRP
      release induced by heat stimulation at 47 degrees C. Employing 45 degrees C
      stimulation intensity, capsazepine and I-RTX (in the higher concentrations)
      showed a significant facilitatory effect on the heat response suggesting a
      partial agonistic action of the compounds. It is concluded that noxious heat
      induced iCGRP release in the isolated rat skin occurs through a mechanism that is
      not inhibited by TRPV1 antagonism reflecting a different pharmacological profile
      of noxious heat transduction in terminals of sensory neurons compared to that in
      cultured cell bodies and TRPV1-transfected host cells.

PMID- 15157690
TI  - Dose-dependent effect of caffeine on reducing leg muscle pain during cycling
      exercise is unrelated to systolic blood pressure.
AB  - This double-blind, within-subjects experiment examined the effects of ingesting
      two doses of caffeine on perceptions of leg muscle pain and blood pressure during
      moderate intensity cycling exercise. Low caffeine consuming college-aged males
      (N=12) ingested one of two doses of caffeine (5 or 10 mg.kg(-1) body weight) or
      placebo and 1 h later completed 30 min of moderate intensity cycling exercise
      (60% VO2peak). The order of drug administration was counter-balanced. Resting
      blood pressure and heart rate were recorded immediately before and 1 h after drug
      administration. Perceptions of leg muscle pain as well as work rate, blood
      pressure, heart rate, and oxygen uptake (VO2) were recorded during exercise.
      Caffeine increased resting systolic pressure in a dose-dependent fashion but
      these blood pressure effects were not maintained during exercise. Caffeine had a
      significant linear effect on leg muscle pain ratings [F(2,22)=14.06; P < 0.0001;
      eta2=0.56 ]. The mean (+/-SD) pain intensity scores during exercise after
      ingesting 10 mg.kg(-1) body weight caffeine, 5 mg.kg(-1) body weight caffeine,
      and placebo were 2.1+/-1.4, 2.6+/-1.5, and 3.5+/-1.7, respectively. The results
      support the conclusion that caffeine ingestion has a dose-response effect on
      reducing leg muscle pain during exercise and that these effects do not depend on
      caffeine-induced increases in systolic blood pressure during exercise.

PMID- 15157691
TI  - Effect of acupuncture treatment on chronic neck and shoulder pain in sedentary
      female workers: a 6-month and 3-year follow-up study.
AB  - The study was carried out to examine whether acupuncture treatment can reduce
      chronic pain in the neck and shoulders and related headache, and also to examine
      whether possible effects are long-lasting. Therefore, 24 female office workers
      (47+/-9 years old, mean+/-SD) who had had neck and shoulder pain for 12+/-9 years
      were randomly assigned to a test group (TG) or a control group (CG). Acupuncture
      was applied 10 times during 3-4 weeks either at presumed anti-pain acupoints (TG)
      or at placebo-points (CG). A physician measured the pain threshold (PPT) in the
      neck and shoulder regions with algometry before the first treatment, and after
      the last one and six months after the treatments. Questionnaires on muscle pain
      and headache were answered at the same occasions and again 3 years after the last
      treatment. The intensity and frequency of pain fell more for TG than for CG (Pb <
      or = 0.04) during the treatment period. Three years after the treatments TG still
      reported less pain than before the treatments (Pw < 0.001) contrary to what CG
      did (Pb < 0.04) The degree of headache fell during the treatment period for both
      groups, but more for TG than for CG (Pb=0.02) Three years after the treatments
      the effect still lasted for TG (Pw < 0.01) while the degree of headache for CG
      was back to the pre-treatment level (Pb < 0.001) PPT of some muscles rose during
      the treatments for TG and remained higher 6 months after the treatments (Pw <
      0.05) which contrasts the situation for CG. Adequate acupuncture treatment may
      reduce chronic pain in the neck and shoulders and related headache. The effect
      lasted for 3 years.

PMID- 15157692
TI  - Nicotine differentially activates inhibitory and excitatory neurons in the dorsal
      spinal cord.
AB  - Nicotinic agonists have well-documented antinociceptive properties when
      administered subcutaneously or intrathecally in mice. However, secondary mild to
      toxic effects are observed at analgesic doses, as a consequence of the activation
      of the large family of differentially expressed nicotinic receptors (nAChRs). In
      order to elucidate the action of nicotinic agonists on spinal local circuits, we
      have investigated the expression and function of nAChRs in functionally
      identified neurons of neonate mice spinal cord. Molecular markers, amplified at
      the single-cell level by RT-PCR, distinguished two neuronal populations in the
      dorsal horn of the spinal cord: GABAergic/glycinergic inhibitory interneurons,
      and calbindin (CA) or NK1 receptor (NK1-R) expressing, excitatory interneurons
      and projection neurons. The nicotinic response to acetylcholine of single cells
      was examined, as well as the pattern of expression of nAChR subunit transcripts
      in the same neuron. Beside the most expressed subunits alpha4, beta2 and alpha7,
      the alpha2 subunit transcript was found in 19% of neurons, suggesting that
      agonists targeting alpha2* nAChRs may have specific actions at a spinal level
      without major supra-spinal effects. Both inhibitory and excitatory neurons
      responded to nicotinic stimulation, however, the nAChRs involved were markedly
      different. Whereas GABA/glycine interneurons preferentially expressed
      alpha4alpha6beta2* nAChRs, alpha3beta2alpha7* nAChRs were preferentially
      expressed by CA or NK1-R expressing neurons. Recorded neurons were also
      classified by firing pattern, for comparison to results from single-cell RT-PCR
      studies. Altogether, our results identify distinct sites of action of nicotinic
      agonists in circuits of the dorsal horn, and lead us closer to an understanding
      of mechanisms of nicotinic spinal analgesia.

PMID- 15157693
TI  - Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated
      phenotypic hypoalgesia.
AB  - Although the N-arachidonoyl ethanolamine (anandamide) binds to cannabinoid
      receptors and has been implicated in the suppression of pain, its rapid
      catabolism in vivo by fatty acid amide hydrolase (FAAH) has presented a challenge
      in investigating the physiological functions of this endogenous cannabinoid. In
      order to test whether anandamide and other non-cannabinoid fatty amides modulate
      nociception, we compared FAAH (+/+) and (-/-) mice in the tail immersion, hot
      plate, and formalin tests, as well as for thermal hyperalgesia in the carrageenan
      and the chronic constriction injury (CCI) models. FAAH (-/-) mice exhibited a CB1
      receptor-mediated phenotypic hypoalgesia in thermal nociceptive tests. These mice
      also exhibited CB1 receptor-mediated hypoalgesia in both phases of the formalin
      test accompanied with a phenotypic anti-edema effect, which was not blocked by
      either CB1 or CB2 antagonists. Additionally, FAAH (-/-) mice displayed thermal
      anti-hyperalgesic and anti-inflammatory effects in the carrageenan model that
      were mediated, in part, by CB2, but not CB1 receptors. In contrast, no genotype
      differences in pain behavior were evident following CCI, which was instead found
      to obliterate the phenotypic hypoalgesia displayed by FAAH (-/-) mice in the tail
      immersion and hot plate tests, suggesting that nerve injury may promote adaptive
      changes in these animals. Collectively, these findings demonstrate a cannabinoid
      receptor-mediated analgesic phenotype in FAAH (-/-) mice. In more general terms,
      these findings suggest that selective inhibitors of FAAH might represent a viable
      pharmacological approach for the clinical treatment of pain disorders.

PMID- 15157694
TI  - Redox modulation of peripheral T-type Ca2+ channels in vivo: alteration of nerve
      injury-induced thermal hyperalgesia.
AB  - We reported recently that redox agents, including the endogenous amino acid L
      cysteine, modulate T-type Ca2+ currents in primary sensory neurons in vitro, and
      alter mechanical and thermal nociception in peripheral nociceptors in vivo in
      intact animals [Neuron 31 (2001) 75]. Here, we studied the effects of locally
      applied redox agents (L-cysteine and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB)
      on thermal hyperalgesia in animals with neuropathic pain due to chronic
      constrictive injury (CCI) of the sciatic nerve. We found that, following
      injection into the peripheral receptive fields, the endogenous reducing agent L
      cysteine increased thermal hyperalgesia in a dose-dependent manner in rats with
      CCI of the sciatic nerve as well as in sham-operated rats. However, the magnitude
      of the increase was smaller and duration of effect was shorter in rats with CCI
      of the sciatic nerve compared to sham-operated animals. DTNB, an exogenous
      oxidizing agent, induced dose-dependent alleviation of thermal hyperalgesia in
      rats with CCI of the sciatic nerve and caused analgesia in sham-operated rats.
      DTNB completely blocked L-cysteine-induced thermal hyperalgesia in both animal
      groups. Mibefradil, a potent and preferential T-type Ca2+ channel blocker,
      abolished L-cysteine-induced increase in thermal hyperalgesia in both animal
      groups suggesting the involvement of T-type Ca2+ channels in peripheral
      nociception. These results indicate for the first time that redox modulation of T
      type Ca2+ channels in rat peripheral nociceptors is operational in pain states
      caused by peripheral axonal injury. Since thermal hyperalgesia is a common
      symptom of axonal injury, locally applied oxidizing agents could be used as a
      novel treatment to ameliorate neuropathic pain.

PMID- 15157695
TI  - Effects of intrathecal injections of melatonin analogs on capsaicin-induced
      secondary mechanical allodynia and hyperalgesia in rats.
AB  - Melatonin, its agonists/antagonists were administered intrathecally (i.t.)
      before/after intradermal injection of capsaicin. Capsaicin produced an increase
      in the paw withdrawal frequency (PWF) in the presumed area of secondary
      mechanical allodynia and hyperalgesia. Melatonin agonists in the absence of a
      capsaicin injection decreased the PWF significantly, whereas melatonin
      antagonists given intrathecally alone were ineffective in the absence of a
      capsaicin injection. Pre-treatment with a melatonin agonist i.t. caused a
      reduction in the PWF after capsaicin. In contrast, the PWF increased after
      capsaicin with pre-administration of a melatonin antagonist i.t. Combined pre
      treatment with melatonin and a melatonin antagonist i.t. prevented the change in
      PWF induced by melatonin alone after capsaicin. Intrathecal post-treatment with a
      melatonin agonist reduced the enhanced PWF that followed an injection of
      capsaicin, but treatment with a combination of a melatonin agonist and its
      antagonist did not alter the responses. The PWF was unaffected when melatonin
      analogs were applied i.t. at the T6 level or were injected intramuscularly
      adjacent to the L4 vertebra. In spinal rats, the data showed comparable effects
      of melatonin analogs on capsaicin-induced secondary mechanical hyperalgesia.
      Animal motor function tested by 'activity box' showed that motion activity was
      not affected by i.t. melatonin or its antagonist. These results suggest that
      activation of the endogenous melatonin system in the spinal cord can reduce the
      generation, development and maintenance of central sensitization, with a
      resultant inhibition of capsaicin-induced secondary mechanical allodynia and
      hyperalgesia.

PMID- 15157696
TI  - Outcomes in acute pain trials: systematic review of what was reported?
AB  - Single-dose clinical trial methods for evaluating analgesics have been used
      successfully for over 50 years. The aims of this review were to examine which
      pain measurement scales have been used in high quality acute pain trials, to
      investigate other common measurements or characteristics, to confirm that
      different scales used by standard methods give the same estimate of analgesic
      effect, to investigate remedication methodologies and the potential of 'time to
      remedication' as a standard outcome. Published reports of randomised, double
      blind, placebo-controlled trials, investigating at least 20 adult patients (10
      patients per treatment arm) experiencing moderate or severe pain using at least
      one standard pain intensity or pain relief scale were sought. Key design
      features, outputs and outcomes were catalogued for each report. The main outcomes
      reported were misleading, detailing only the mean values of data with a
      demonstrably skewed distribution. After 50 years, the reporting of results from
      acute pain trials warrants a fresh look. Possible improvements include reporting
      the number of patients with certain levels of pain relief, or the actual number
      (percentage) of patients with a certain level of pain relief at a certain time,
      or more useful information on remedication from trials of at least 12 h duration.
      Most useful would be all three. Further exploration would only be possible from
      analysis at the individual patient level.

PMID- 15157697
TI  - Allodynia in patients with post-stroke central pain (CPSP) studied by statistical
      quantitative sensory testing within individuals.
AB  - The disinhibition hypothesis of post-stroke central pain (CPSP) suggests that
      'the excessive response (dysesthesia/hyperalgesia/allodynia) is accompanied by a
      em leader loss of sensation' resulting from a lesion of a 'lateral nucleus' of
      thalamus or of 'cortico-thalamic paths' [Brain 34 (1911) 102]. One recent
      elaboration of this hypothesis proposes a submodality specific relationship, such
      that injury to a cool-signaling lateral thalamic pathway disinhibits a
      nociceptive medial thalamic pathway, thereby producing both burning, cold,
      ongoing pain and cold allodynia. The current study quantitatively evaluated the
      sensory loss and sensory abnormalities to discern submodality relationships
      between these sensory features of CPSP. The present results were statistically
      tested within individuals so that sensory loss and sensory abnormality are
      directly related by occurrence in the same individual. The results demonstrate
      that individuals with CPSP and normal tactile detection thresholds experience
      tactile allodynia significantly more often than those with tactile hypoesthesia.
      Most patients (11/13) exhibited hypoesthesia for the perception of cool stimuli,
      but few of these (2/11) showed cold allodynia. The most dramatic case of cold
      allodynia occurred in a patient who had a normal detection threshold for cold.
      Individuals with cold hypoesthesia, strictly contralateral to the cerebro
      vascular accident (CVA or stroke), were often characterized by the presence of
      burning, cold, ongoing pain, and by the absence, not the presence, of cold
      allodynia. Overall, these results in CPSP suggest that tactile allodynia occurs
      in disturbances of thermal/pain pathways that spare the tactile-signaling
      pathways, and that cold hypoesthesia is neither necessary nor sufficient for cold
      allodynia.

PMID- 15157698
TI  - Differential modulation of nociceptive dural input to [hypocretin] orexin A and B
      receptor activation in the posterior hypothalamic area.
AB  - The novel neuropeptides orexin A and B are selectively synthesised in the lateral
      and posterior hypothalamus and are involved in hypothalamic regulation of
      autonomic and neuroendocrine functions. Recent findings point also to a role in
      nociception. As the posterior hypothalamus is involved in the central modulation
      of nociception we studied the effects of hypocretin/orexin receptor activation in
      the posterior hypothalamic area (PH) of the rat on dural nociceptive input.
      Orexins were microinjected into the PH and the effects on responses of neurones
      in the caudal trigeminal nucleus studied. Injection of orexin A decreased the A-
      and C-fibre responses to dural electrical stimulation as well as spontaneous
      activity. Responses to noxious thermal stimulation of the facial skin were also
      decreased by orexin A. Injection of orexin B into the PH, however, elicited
      increased responses to dural stimulation in A- and C-fibre responses and resulted
      in increased spontaneous activity. Responses to facial thermal stimulation were
      also increased by orexin B. Control injection of saline into the PH had no
      significant effect. The results show a differential modulation of dural
      nociceptive input by orexin A and B receptor activation in the PH. The results
      support the role of the PH in the nociceptive processing of meningeal input. As
      both peptides are also involved in hypothalamic regulation of neuroendocrine and
      autonomic functions, orexinergic mechanisms in the PH may provide a link for
      endocrine and autonomic changes as well as nociceptive phenomena seen in primary
      headache disorders.

PMID- 15157699
TI  - Mechanical allodynia following contusion injury of the rat spinal cord is
      associated with loss of GABAergic inhibition in the dorsal horn.
AB  - The present study investigated whether mechanical allodynia following contusive
      spinal cord injury (SCI) of the thoracic segments 12 and 13 of the rat was
      associated with a reduction in gamma-aminobutyric acid (GABA)ergic inhibition
      adjacent to the site of injury. Five to 7 days following SCI, extracellular
      recordings were obtained from dorsal horn neurones located 1-2 segments caudal to
      the injury, in non-allodynic and allodynic halothane anaesthetised rats and from
      comparable neurones in normal rats. To assess spinal GABAergic inhibition in the
      three groups of animals, spontaneous and evoked cell firing rates were recorded
      before, during and after microiontophoretic application of the GABA(A) receptor
      antagonist bicuculline. Administration of bicuculline to normal animals resulted
      in significant and reversible increases in the receptive field size, spontaneous
      firing rate, response to brushing and pinching the skin and afterdischarge
      activity of dorsal horn neurones, as well as decreasing paired-pulse depression
      of responses evoked by transcutaneous electrical stimulation. In non-allodynic
      SCI animals, bicuculline ejection led to significant changes in receptive field
      size, paired-pulse depression and responses to brush and pinch stimulation that
      were comparable to those observed in normal animals. By contrast, in allodynic
      SCI animals, bicuculline ejection had little or no effect on dorsal horn neurone
      responses to mechanical skin stimuli and paired-pulse depression despite reliably
      blocking the inhibition of cell firing produced by similarly applied GABA. The
      demonstration of reduced GABAergic inhibition predominantly in the allodynic SCI
      rats suggests that such a deficiency contributed to this pain-related behaviour
      acutely following SCI.

PMID- 15157700
TI  - Reasons for missing interviews in the daily electronic assessment of pain, mood,
      and stress.
AB  - Electronic diary assessment methods offer the potential to accurately
      characterize pain and other daily experiences. However, the frequent assessment
      of experiences over time often results in missing data. It is important to
      identify systematic reasons for missing data because such a pattern may bias
      study results and interpretations. We examined the reasons for missing electronic
      interviews, comparing self-report and data derived from electronic diary
      responses. Sixty-two patients with temporomandibular disorders were asked to rate
      pain intensity, pain-related activity interference, jaw use limitations, mood,
      and perceived stress three times a day for 8 weeks on palmtop computers.
      Participants also were asked the number of and reason(s) for missing electronic
      interviews. The average electronic diary completion rate was 91%. The
      correspondence between self-report and electronic data was high for the overall
      number of missed electronic interviews (Spearman correlation=0.77, P < 0.0001).
      The most common self-reported reasons for missing interviews were failure to hear
      the computer alarm (49%) and inconvenient time (21%). Although there was some
      suggestion that persistent negative mood and stress were associated with missing
      electronic interviews in a subgroup of patients, on the whole, the patient
      demographic and clinical characteristics, treatment, and daily fluctuations in
      pain, activity interference, mood, and stress were not associated significantly
      with missing daily electronic interviews. The results provide further support for
      the use of electronic diary methodology in pain research.

PMID- 15157701
TI  - Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain
      during pain--an fMRI analysis.
AB  - Neuroimaging studies with positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI) have delineated a human pain network in vivo.
      Despite the recognition of cerebral structures engaged in pain transmission, the
      cerebral mechanisms involved in pain modulation are still not well understood.
      Here, we investigated healthy volunteers using fMRI during experimental heat pain
      and distraction induced by a visual incongruent color-word Stroop task. A
      factorial design permitted categorical and covariation analysis of four
      conditions, namely innocuous and noxious heat; with and without distraction. Pain
      without distraction evoked an activation pattern similar to that observed in
      previous neuroimaging pain studies. Distraction was associated with a significant
      reduction of the visual analogue scale (VAS) ratings for pain intensity and
      unpleasantness and a reduction of pain-related activation in multiple brain
      areas, particularly in the so-called 'medial pain system'. Distraction
      significantly increased the activation of the cingulo-frontal cortex including
      the orbitofrontal and perigenual anterior cingulate cortex (ACC), as well as the
      periaquaeductal gray (PAG) and the posterior thalamus. Covariation analysis
      revealed functional interaction between these structures during pain stimulation
      and distraction, but not during pain stimulation per se. According to our
      results, the cingulo-frontal cortex may exert top-down influences on the PAG and
      posterior thalamus to gate pain modulation during distraction.

PMID- 15157702
TI  - Antinociceptive action of a p38alpha MAPK inhibitor, SD-282, in a diabetic
      neuropathy model.
AB  - Diabetes can induce a bewildering list of sensory changes, including alteration
      in pain sensitivity. Painful diabetic neuropathy is refractory to most common
      analgesics. This study examined the effect of a p38alpha MAPK inhibitor, SD-282,
      on mechanical allodynia, thermal hyperalgesia, and formalin-evoked nociception in
      streptozotocin-induced diabetic rats. Four-week diabetic rats exhibited
      mechanical allodynia, decreased mechanical thresholds, and C- and Adelta-fiber
      mediated thermal hyperalgesia. Mechanical and thermal responses were measured in
      diabetic rats following acute and repeated intraperitoneal administration of
      vehicle, 15 or 45 mg/kg SD-282. Mechanical allodynia was reversed by acute and
      repeated administration of 15 and 45 mg/kg SD-282. Repeated administration of 15
      or 45 mg/kg SD-282 prevented the exacerbation of C-, but not Adelta-fiber,
      mediated thermal hyperalgesia. Repeated administration of 45 mg/kg SD-282
      attenuated flinching behaviors during the quiescent period and the second phase
      of the formalin response in diabetic rats. Acute and repeated administration of
      15 or 45 mg/kg SD-282 had no effect on mechanical, thermal or formalin responses
      in age-matched control rats. These results indicate a potential therapeutic value
      of p38alpha MAPK inhibitors in the treatment of aberrant pain sensitivity
      produced by diabetes.

PMID- 15157703
TI  - Systematic review of prognostic cohort studies on shoulder disorders.
AB  - Shoulder complaints are common and have an unfavourable outcome in many patients.
      Only 50% of all new episodes of shoulder disorders end in complete recovery
      within 6 months. There is no consensus about prognostic indicators that can
      identify patients at high and low risk of chronicity. By a systematic search of
      the literature we identified 16 studies focusing on the prognosis of shoulder
      disorders. The methodological quality of these 16 studies was assessed. Six of
      these were considered to be of relatively 'high quality'. There was a wide
      variety among the studies in length of follow-up, study population, evaluated
      prognostic factors, type of outcome measure and method of analysis. Due to this
      large heterogeneity, we refrained from statistical pooling. Instead, we used a
      best-evidence synthesis. There is strong evidence that high pain intensity
      predicts a poorer outcome in primary care populations and that middle age (45-54)
      is associated with poor outcome in occupational populations. There is moderate
      evidence that a long duration of complaints, and high disability score at
      baseline predict a poorer outcome in primary care. These results need to be
      interpreted with caution because of the small number of studies on which these
      conclusions are based, and the large heterogeneity among studies regarding follow
      up, outcome measures, and analysis.

PMID- 15157704
TI  - Activation of peripheral cannabinoid receptors attenuates cutaneous hyperalgesia
      produced by a heat injury.
AB  - Accumulating evidence suggests that cannabinoids can produce antinociception
      through peripheral mechanisms. In the present study, we determined whether
      cannabinoids attenuated existing hyperalgesia produced by a mild heat injury to
      the glabrous hindpaw and whether the antihyperalgesia was receptor-mediated.
      Anesthetized rats received a mild heat injury (55 degrees C for 30 s) to one
      hindpaw. Fifteen minutes after injury, animals exhibited hyperalgesia as
      evidenced by lowered withdrawal latency to radiant heat and increased withdrawal
      frequency to a von Frey monofilament (200 mN force) delivered to the injured
      hindpaw. Separate groups of animals were then treated with an intraplantar
      (i.pl.) injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2 at
      doses of 1, 10, or 30 microg in 100 microl. WIN 55,212-2 attenuated both heat and
      mechanical hyperalgesia dose-dependently. The inactive enantiomer WIN 55,212-3
      did not alter mechanical or heat hyperalgesia, suggesting the effects of WIN
      55,212-2 were receptor-mediated. The CB1 receptor antagonist AM 251 (30 microg)
      co-injected with WIN 55,212-2 (30 microg) attenuated the antihyperalgesic effects
      of WIN 55,212-2. The CB2 receptor antagonist AM 630 (30 microg) co-injected with
      WIN 55,212-2 attenuated only the early antihyperalgesic effects of WIN 55,212-2.
      I.pl. injection of WIN 55,212-2 into the contralateral paw did not alter the heat
      injury induced hyperalgesia, suggesting that the antihyperalgesia occurred
      through a peripheral mechanism. These data demonstrate that cannabinoids
      primarily activate peripheral CB1 receptors to attenuate hyperalgesia. Activation
      of this receptor in the periphery may attenuate pain without causing unwanted
      side effects mediated by central CB1 receptors.

PMID- 15157705
TI  - Electrophysiological characterization of N-methyl-D-aspartate receptors in rat
      dorsal root ganglia neurons.
AB  - In the peripheral nervous system, N-methyl-D-aspartate receptors (NMDAR)
      expressed on the central and peripheral terminals of primary afferent neurons are
      involved in nociception. We used single cell imaging of intracellular calcium
      concentration ([Ca2+]i) and patch clamp techniques to characterize the functional
      properties of NMDARs on adult rat dorsal root ganglia (DRG) neurons in primary
      culture and selectively on those innervating the distal colon. In Mg2+-free
      extracellular solution, rapid perfusion of DRG neurons with 250 microM NMDA and
      10 microM glycine caused a significant increase in [Ca2+]i, and elicited inward
      currents in whole cell patch clamp recordings when the holding potential was -60
      mV. Both effects were reversibly inhibited by 200 microM ketamine in a use
      dependent manner. The EC50 values for NMDA and glycine were 64 and 1.9 microM
      with Hill slope coefficients of 1.4 and 1.3, respectively. At negative
      potentials, extracellular Mg2+ blocked currents in a concentration- and voltage
      dependent manner. The IC50 for Mg2+ at a holding potential of -100 mV was 2.0
      microM. The NMDAR subtype-selective antagonist, ifenprodil, inhibited 94% of the
      NMDA and glycine-induced current with an IC50 of 2.6 microM. There was no
      evidence of multiple binding sites for ifenprodil. There was no significant
      difference in the NMDAR current density on DRG neurons that had innervated the
      colon, nor was there a difference in the EC50 for ifenprodil. These results
      demonstrate that functional NMDARs expressed by DRG neurons innervating both
      somatic and visceral tissues of adult rats are composed predominantly of NR2B
      subunits.

PMID- 15157706
TI  - Modulation of the gait deficit in arthritic rats by infusions of muscimol and
      bicuculline.
AB  - Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was
      used to examine the role of GABA(A) receptors in the development of pain. Drug
      solutions were administered continuously at 5+/-0.75 microl/h for 14 days via
      Alzet osmotic pumps (2ML2) placed under the skin of the back. The GABA(A)
      receptor agonist, muscimol, produces a dose-dependent reversal of the gait
      deficits seen in arthritic rats without reducing the tibiotarsal joints
      inflammatory edema or the histological picture of joint erosion and inflammation.
      The higher infusion rate for muscimol, 20 microg/h, caused the gait for the
      arthritic rats to be indistinguishable from that of normal non-arthritic rats. In
      normal, non-arthritic rats, muscimol did not show any effect on gait. The GABA(A)
      receptor antagonist bicuculline showed small but significant exacerbation of
      stride length (P < 0.05) single and double stance time (P < 0.05) and swing time
      deficits (P < 0.05) in the arthritic rats, but no changes in measures of gait in
      the normal control rat. The results suggest that the development of arthritic
      pain is increased in the absence of GABA(A) receptor tone and that increasing
      GABA(A) receptor tone can reduce arthritic pain but does not affect the disease
      process.

PMID- 15157707
TI  - Development and validation of the Child Activity Limitations Interview: a measure
      of pain-related functional impairment in school-age children and adolescents.
AB  - Recurrent pain in childhood are common and frequently impact children's everyday
      functioning. However, there are currently limited tools available to measure the
      impact of recurrent pain on children's daily activities, in particular, that can
      be used to identify appropriate targets for intervention and measure response to
      such interventions. The purpose of this study was to develop and validate a new
      measure, the Child Activity Limitations Interview (CALI), to improve the
      assessment of functional impairment due to recurrent pain in school-age children
      and adolescents, and to compare this measure to the Functional Disability
      Inventory. Participants included 189 children, aged 8-16 years (M=12.4, SD 2.5),
      60% female, 40% minority, who were part of a longitudinal study of recurrent pain
      in children with headaches, juvenile idiopathic arthritis, and sickle cell
      disease. Measures of socio-demographics, pain, anxiety and depression, and
      functional disability were completed. A subset of participants (47%) were re
      administered the CALI 1 month later and completed prospective ratings of pain and
      activity limitations using the CALI in daily diaries. Internal consistency of the
      CALI was excellent (alpha=0.88, child version; alpha=0.95, parent version). One
      month test-retest reliability (r = 0.33, child report) and cross-informant
      reliability (r = 0.43) were moderate. Results demonstrate support for face,
      construct, and concurrent validity as well as responsiveness to pain symptom
      fluctuation. Findings demonstrate that the CALI is a promising measure for
      assessing and monitoring subjective report of functional impairment in school-age
      children and adolescents with recurrent and chronic pain.

PMID- 15157708
TI  - Absence of an association between axotomy-induced changes in sodium currents and
      excitability in DRG neurons from the adult rat.
AB  - It is generally believed that nerve injury results in neuronal hyperexcitability
      that reflects in part a change in Na+ currents. However, there are conflicting
      data on the nature of Na+ current changes and the association between alterations
      in Na+ currents and increases in excitability. One potential source of
      conflicting data is that injured and spared neurons may respond differently to
      nerve injury; these subpopulations of neurons have not been distinguished in
      previous studies with the axotomy model of nerve injury (complete transection of
      the sciatic nerve). The present study was performed to determine the relationship
      between changes in Na+ channels and changes in neuronal excitability in
      identified injured dorsal root ganglion neurons post-axotomy. Small (< 45 pF)
      neurons labeled with a DiI injection into the sciatic nerve were studied 10 days
      and 4 weeks post-axotomy. Ten days post-axotomy, tetrodotoxin-resistant (TTX-R)
      Na+ current (INa) was decreased and TTX-sensitive (TTX-S) INa was increased,
      however, excitability was unchanged. Four weeks post-axotomy, neurons had become
      hyperexcitable while TTX-R INa remained reduced and TTX-S INa had returned to
      control levels. Thus, axotomy-induced changes in Na+ currents were not correlated
      with an axotomy-induced change in excitability. Additional analysis of axotomized
      neurons suggested that concomitant changes in other ionic currents occurred.
      These results suggest that neuronal excitability following axotomy is dependent
      on the sum of changes in ionic currents, and the overall effect on excitability
      may not always correspond to that predicted by a change in a single class of
      voltage-gated ion channel.

PMID- 15157709
TI  - Gender differences in post-operative pain and patient controlled analgesia use
      among adolescent surgical patients.
AB  - The aim of this study was to explore gender differences in anticipatory emotional
      distress, coping strategies, post-operative pain perception, and patient
      controlled analgesia (PCA) use among adolescent surgical patients. One hundred
      and two 12-18-year-old adolescents undergoing surgeries with overnight hospital
      stay were recruited. Participants completed pre-operative measures of anxiety and
      anticipated pain. Post-operatively, they reported on coping skills, post
      operative anxiety, and pain. Data on PCA use were recorded from medical records.
      Girls reported higher levels of pre-operative state anxiety and anticipated more
      pain. After surgery, girls and boys differed on their lowest daily pain ratings
      and average daily pain ratings, with girls reporting more pain in both cases.
      Reports of highest daily pain were similar across genders. Gender was found to
      moderate the relationship between anticipatory distress and post-operative pain,
      such that higher anticipatory distress before surgery predicted more post
      operative pain for girls, but not for boys. Patterns of PCA use did not vary by
      gender on post-operative days 0 or 1. Findings suggest that adolescent boys' and
      girls' pain experiences are different in several important respects, although
      somewhat less divergent than has been reported in samples of adult males and
      females. Results have implications for the development of targeted intervention
      strategies to help adolescents cope effectively with acute post-operative pain.

PMID- 15157711
TI  - Exercise lowers pain threshold in chronic fatigue syndrome.
AB  - Post-exertional muscle pain is an important reason for disability in patients who
      are diagnosed to have Chronic Fatigue Syndrome (CFS). We compared changes in pain
      threshold in five CFS patients with five age and sex matched controls following
      graded exercise. Pain thresholds, measured in the skin web between thumb and
      index finger, increased in control subjects with exercise while it decreased in
      the CFS subjects. Increased perception of pain and/or fatigue after exercise may
      be indicative of a dysfunction of the central anti-nociceptive mechanism in CFS
      patients.

PMID- 15157710
TI  - Genetic influence on variability in human acute experimental pain sensitivity
      associated with gender, ethnicity and psychological temperament.
AB  - While a variety of cultural, psychological and physiological factors contribute
      to variability in both clinical and experimental contexts, the role of genetic
      factors in human pain sensitivity is increasingly recognized as an important
      element. This study was performed to evaluate genetic influences on variability
      in human pain sensitivity associated with gender, ethnicity and temperament. Pain
      sensitivity in response to experimental painful thermal and cold stimuli was
      measured with visual analogue scale ratings and temperament dimensions of
      personality were evaluated. Loci in the vanilloid receptor subtype 1 gene
      (TRPV1), delta opioid receptor subtype 1 gene (OPRD1) and catechol O
      methyltransferase gene (COMT) were genotyped using 5' nuclease assays. A total of
      500 normal participants (306 females and 194 males) were evaluated. The sample
      composition was 62.0% European American, 17.4% African American, 9.0% Asian
      American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage.
      Female European Americans with the TRPV1 Val(585) Val allele and males with low
      harm avoidance showed longer cold withdrawal times based on the classification
      and regression tree (CART) analysis. CART identified gender, an OPRD1
      polymorphism and temperament dimensions of personality as the primary
      determinants of heat pain sensitivity at 49 degrees C. Our observations
      demonstrate that gender, ethnicity and temperament contribute to individual
      variation in thermal and cold pain sensitivity by interactions with TRPV1 and
      OPRD1 single nucleotide polymorphisms.

PMID- 15157712
TI  - Catastrophizing and perceived partner responses to pain.
AB  - This study examined the relationship between catastrophizing and patient
      perceived partner responses to pain behaviors. The Catastrophizing subscale of
      the Cognitive Coping Strategy Inventory and the West Haven-Yale Multidimensional
      Pain Inventory were completed by 62 adult chronic pain patients. Consistent with
      past research, catastrophizing and patient-perceived solicitous partner behaviors
      were positively correlated with negative pain outcomes. The communal coping
      theory of catastrophizing suggests that catastrophizing might be undertaken to
      solicit support and empathy from others. However, catastrophizing was not related
      to perceived solicitous partner behavior in this study. Rather, catastrophizing
      was associated with perceived punishing partner responses. Implications are that
      catastrophizing and perceived solicitous partner behaviors are independently
      associated with pain and that catastrophizing may not be reinforced by empathy
      from significant others.

PMID- 15157713
TI  - Ontogeny of analgesia elicited by non-nutritive suckling in acute and persistent
      neonatal rat pain models.
AB  - Significant analgesic and calming effects in human infants and neonatal rodents
      are produced by orogustatory and orotactile stimuli associated with nursing.
      These naturally occurring analgesic stimuli may help to protect the vulnerable
      developing nervous system from the long-term effects of neonatal tissue injury.
      However, the efficacy of orotactile-induced analgesia across the pre-weaning
      period, as well as its effects on persistent inflammatory pain, is unknown. Here,
      we investigated the developmental profile of analgesia produced by orotactile
      stimulation during non-nutritive suckling in rats. The effects of suckling, as
      compared to non-suckling littermates, on nocifensive withdrawal responses to
      thermal and mechanical stimuli were examined at postnatal (P) days P0, P3, P10,
      P17 and P21. In some rats, Complete Freund's adjuvant (CFA) was injected in a
      fore- or hindpaw to produce inflammation. For thermal stimuli, suckling
      significantly increased forepaw withdrawal latencies at P3, P10 and P17, while
      hindpaw responses were increased at P3 and P10, but not at P17. In inflamed pups,
      suckling increased fore- and hindpaw response latencies at P10 and P17, but not
      at P0 or P21. Suckling-induced analgesia was naloxone-insensitive. For mechanical
      stimuli, suckling-induced analgesia was present at P3, P10 and P17, but not at
      P21, for both fore- and hindpaws in naive and inflamed animals. Additionally,
      suckling had a small but significant effect at P0 for the forepaw in inflamed
      pups. In nearly all experiments, the peak effect of suckling for thermal and
      mechanical stimuli occurred at P10. These results indicate that orotactile
      analgesia, like orogustatory analgesia, is absent or minimal at P0, appears
      consistently at approximately P3 and is maximal at P10. Unlike gustatory
      analgesia in rats however, orotactile analgesia persists at least to P17.
      Orotactile stimulation during suckling effectively reduces transient pain
      elicited by thermal and mechanical stimuli, as well as persistent hyperalgesia
      and allodynia caused by inflammation.

PMID- 15157715
TI  - New techniques for surgical management of trigeminal neuralgia.

PMID- 15157714
TI  - Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980
      vs. 2000.
AB  - The treatment of pain has received increasing attention over the past decade
      promoted by national guidelines, the 'pain as the 5th vital sign' campaign and
      direct-to-consumer advertising. We examined national trends in office visits and
      analgesic treatment for musculoskeletal pain in the office setting, comparing
      data from 1980 and 2000. We analysed the National Ambulatory Medical Care Survey
      (NAMCS)--a nationally representative survey of visits to office-based physicians-
      using data from 1980-81 (n=89,000 visits) and 1999-2000 (n=45,000 visits). During
      this time, NSAID prescriptions increased for both acute (19 vs. 33%, RR=1.74; 95%
      CI, 1.52-1.95) and chronic (25 vs. 29%, RR=1.16; 95% CI, 0.97-1.35)
      musculoskeletal pain visits. In 2000, one-third of the NSAID prescriptions were
      for COX II agents. Opioids increased for acute pain (8 vs. 11%, RR=1.38; 95% CI,
      0.92-1.83) and doubled for chronic pain (8 vs. 16%, RR=2.0; 95% CI, 1.52-2.48).
      The use of more potent opioids (hydrocodone, oxycodone, morphine) for chronic
      musculoskeletal pain increased from 2 to 9% of visits (RR=4.5; 95% CI, 2.18
      6.87). This corresponds to 5.9 million visits where potent opioids were
      prescribed in 2000--an increase of 4.6 million visits from 1980 (assuming the
      total number of outpatient visits was constant at the 2000 level). In spite of
      the increased attention to pain treatment, there has not been an increase in
      office visits for musculoskeletal pain complaints. The threshold for prescribing
      NSAIDS and opioids, however, has dropped.

PMID- 15157717
TI  - "Marchand S, Kupers RC, Bushnell MC, Duncan GH. Analgesic and placebo effects of
      thalamic stimulation. Pain 2003;105:481-8".

PMID- 15157719
TI  - Comment on: Increased pain sensitivity in fibromyalgia: effects of stimulus type
      and mode of presentation, Petzke et al., Pain 105 (2003) 403-413, and the related
      editorial: Hyperalgesia versus response bias in fibromyalgia, Fillingim, Pain,
      105 (2003) 385-386.

PMID- 15157721
TI  - Transforaminal epidural steroid delivery and diagnosing the level of nerve root
      pathology: comments on Baker et al., Pain 103/1-2, 2003.

PMID- 15157723
TI  - Letter to the editor from Dr Kenneth McHenry referring to Giardino 15220.

PMID- 15157725
TI  - Cellular and genetic regulation of the development of the cerebellar system.
AB  - Recent advances in molecular biology have drastically changed our vision on the
      development of the nervous system, the cerebellum in particular. After a
      classical descriptive period, we are now in a modern mechanistic epoch as we
      begin to answer crucial questions in our quest to understand the mechanisms
      underlying the emergence of brain complexity. This review begins with an analysis
      of the role of the "isthmic organizer" in the induction and specification of the
      cerebellar territory and progresses through cerebellar development to the
      formation of cerebellar maps. It gathers information about the control of the
      proliferation of granule cell precursors by Purkinje cells and the role of
      Shh/Gli-patched signaling. The migratory routes for cerebellar and precerebellar
      neurons, together with the long-range and short-range cues guiding gliophilic
      and, particularly, neurophilic migrations, are also discussed. Because these cues
      are similar to those involved in axon guidance, both processes are under the same
      molecular constraints. Finally, using primarily the olivocerebellar projection as
      a model, the cellular and molecular mechanisms involved in the formation of
      cerebellar maps are discussed. During embryonic development, Purkinje cells in
      the cerebellum and neurons in the inferior olive follow a simultaneous, but
      independent, process of intrinsic parcellation, giving rise to subsets of
      biochemically different cortical compartments. The occurrence of positional
      information shared between olivary axons and their postsynaptic targets, the
      Purkinje cells, provides a molecular code for the formation of coarse-grained
      maps. Activity-dependent mechanisms are required for the transition from crude to
      fine-grained maps. This important refinement, which confers ultimate specificity
      to the maps, is under the regulation of parallel fiber-Purkinje cell synaptic
      activity.

PMID- 15157726
TI  - The functional neuroanatomy of the human orbitofrontal cortex: evidence from
      neuroimaging and neuropsychology.
AB  - The human orbitofrontal cortex is an important brain region for the processing of
      rewards and punishments, which is a prerequisite for the complex and flexible
      emotional and social behaviour which contributes to the evolutionary success of
      humans. Yet much remains to be discovered about the functions of this key brain
      region, and new evidence from functional neuroimaging and clinical
      neuropsychology is affording new insights into the different functions of the
      human orbitofrontal cortex. We review the neuroanatomical and neuropsychological
      literature on the human orbitofrontal cortex, and propose two distinct trends of
      neural activity based on a meta-analysis of neuroimaging studies. One is a
      mediolateral distinction, whereby medial orbitofrontal cortex activity is related
      to monitoring the reward value of many different reinforcers, whereas lateral
      orbitofrontal cortex activity is related to the evaluation of punishers which may
      lead to a change in ongoing behaviour. The second is a posterior-anterior
      distinction with more complex or abstract reinforcers (such as monetary gain and
      loss) represented more anteriorly in the orbitofrontal cortex than simpler
      reinforcers such as taste or pain. Finally, we propose new neuroimaging methods
      for obtaining further evidence on the localisation of function in the human
      orbitofrontal cortex.

PMID- 15157727
TI  - Mounting a community-randomized trial: sample size, matching, selection, and
      randomization issues in PRISM.
AB  - This paper discusses some of the processes for establishing a large cluster
      randomized trial of a community and primary care intervention in 16 local
      government areas in Victoria, Australia. The development of the trial in terms of
      design factors such as sample size estimates and the selection and randomization
      of communities to intervention or comparison is described. The intervention
      program to be implemented in Program of Resources, Information and Support for
      Mothers (PRISM) was conceived as a whole community approach to improving support
      for all mothers in the first 12 months after birth. A cluster-randomized trial
      was thus the design of choice from the outset. With a limited number of
      communities available, a matched-pair design with eight pairs was chosen. Sample
      size estimates, adjusting for the cluster randomization and the pair-matched
      design, showed that with eight pairs, on average, 800 women from each community
      would need to respond to provide sufficient power to determine a 3% reduction in
      the prevalence of maternal depression 6 months after birth-a reduction deemed to
      be a worthwhile impact of the intervention to be reliably detected at 80% power.
      The process of selecting suitable communities and matching them into pairs
      required careful collection of data on numbers of births, size of the local
      government areas (LGAs), and an assessment of the capacity of communities to
      implement the intervention. Ways of dealing with boundary issues associated with
      potential contamination are discussed. Methods for the selection of feasible
      configurations of sets of pairs and the ultimate allocation to intervention or
      comparison are provided in detail. Ultimately, all such studies are a balancing
      act between selecting the minimum number of communities to detect a meaningful
      outcome effect of an intervention and the maximum size budget and other resources
      allow.

PMID- 15157728
TI  - Widening eligibility to phase II trials: constant arcsine difference phase II
      trials.
AB  - This paper presents a method for undertaking Phase II trials in which not all
      patients are considered equally likely to respond to treatment. In ovarian
      cancer, for example, it has been shown that response is less likely in patients
      who have failed the previous treatment after only a short interval compared to
      those who have a protracted failure-free interval [Gynecol. Oncol. 36 (1990)
      207]. The method is analogous to those used in phase III trials which estimate
      relative rather than absolute effects; a constant odds ratio, for example,
      encompasses multiple relationships between response rates. Phase II trials
      commonly test the null hypothesis H(0): P<or=p(0) against the alternate
      hypothesis H(1): P>or=p(1), where the response rate p(1) is the minimum required
      level of efficacy and p(0) the highest level which would indicate that the
      treatment is of no further interest. This approach can be extended by using the
      arcsine transformation to allow p(0) and p(1) to vary between patients, thus for
      the ith patient p(0i)=(sin c(i))(2) and the efficacy level is set to p(1i)=(sin
      (c(i)+b))(2). The value of the arcsine parameter b therefore determines efficacy
      and the test for efficacy in the trial then becomes a test of the null hypothesis
      H(0): B<or=0 against the alternate hypothesis H(1): B>or=b. The value of b is
      determined by considering representative values of p(0) and p(1) and setting
      b=(sin(-1) radical p(1)-sin(-1) radical p(0)); b is thus the constant arcsine
      difference (CAD) between p(0i) and p(1i). The variance of B is 1/4n, which is
      independent of P, trial designs are therefore independent of P, implying that all
      patients for whom this difference is identical can be entered into the same
      trial. This paper considers single-stage and two-stage CAD Phase II trials.

PMID- 15157729
TI  - Quality of life intervention for prostate cancer patients: design and baseline
      characteristics of the active for life after cancer trial.
AB  - Prostate cancer patients receiving androgen ablation therapy experience
      significant physical and psychological sequelae associated with their disease and
      treatment. Because physical activity improves physical and psychological well
      being, a lifestyle physical activity intervention may help slow or reverse the
      associated decline in quality of life (QOL). No studies have evaluated an
      intervention to improve multiple QOL domains in patients receiving androgen
      ablation therapy. Active for Life After Cancer is a three-group randomized
      controlled trial designed to evaluate the effectiveness of a lifestyle physical
      activity intervention (Lifestyle Program) in improving QOL. The Lifestyle
      Program, a 6-month behavioral skills training group, is compared to an
      Educational Support Program and Standard Care. The purpose of this paper is to
      describe the design of the randomized trial and present baseline data that will
      characterize the QOL of the sample. Challenges to recruitment for the trial also
      will be presented and discussed.

PMID- 15157730
TI  - The Prevention of Early Asthma in Kids study: design, rationale and methods for
      the Childhood Asthma Research and Education network.
AB  - Pediatric asthma remains an important public health concern as its prevalence and
      cost to the health care system is rising. In order to promote innovative research
      in asthma therapies, the National Heart, Lung and Blood Institute created the
      Childhood Asthma Research and Education Network in 1999. As its first study, the
      steering committee of the Childhood Asthma Research and Education Network
      designed a randomized clinical trial to determine if persistent asthma could be
      prevented in children at a high risk to develop the disease. This communication
      presents the design of its first clinical trial, the Prevention of Asthma in Kids
      (PEAK) trial and the organization of the Childhood Asthma Research and Education
      Network that developed and implemented this trial. Studies of the natural history
      of asthma have shown that, in persistent asthma, the initial asthma-like symptoms
      and loss of lung function occur predominately during the first years of life.
      Therefore, in the Prevention of Asthma in Kids study, children 2 and 3 years old
      with a positive asthma predictive index were randomized to twice daily treatment
      with fluticasone 88 microg or placebo via metered-dose inhaler and Aerochamber
      for 2 years. The double blind treatment period was followed by a 1-year
      observational period. Lung function was measured by spirometry and oscillometry
      technique at 4-month intervals throughout the study. Bronchodilator reversibility
      and exhaled nitric oxide (ENO) studies were performed at the end of the treatment
      and observation periods. The primary outcome measure was the number of asthma
      free days. Other secondary outcomes included number of exacerbations, use of
      asthma medications and lung function. These measures were chosen to reflect the
      progression of the disease from intermittent wheezing to persistent asthma and
      measurement of the extent of airflow limitation and airway reactivity.

PMID- 15157731
TI  - Multicenter trial of early treatment for retinopathy of prematurity: study
      design.
AB  - The Early Treatment for Retinopathy of Prematurity (ETROP) study was a
      randomized, prospective multicenter trial comparing the safety and efficacy of
      earlier vs. conventionally timed ablation of the peripheral retina for the
      management of moderate to severe retinopathy of prematurity (ROP). Approximately
      7000 infants with birth weights <1251 g were screened at 26 centers over a 2-year
      period to achieve the sample size of 401 consented infants for the randomized
      trial. In order to minimize treatment of eyes with ROP that were likely to
      undergo spontaneous regression of the disease, a risk analysis model, RM-ROP2,
      was used to select for inclusion in the randomized trial only prethreshold eyes
      that had a high risk of an adverse outcome. The primary outcome measure was
      grating visual acuity measured by Teller acuity card testing conducted by masked
      testers in eyes randomized to earlier treatment vs. eyes randomized to
      conventional management when infants were 9 months post-term. Results were
      categorized into favorable (>or=1.85 cycles/degree) vs. unfavorable (<1.85
      cycles/degree). The secondary outcome measure was retinal structure, assessed by
      ophthalmological examinations conducted at 6 and 9 months post-term. Here we
      describe a unique approach used in the ETROP study to select high-risk
      prethreshold ROP eyes for randomization and details about design of the study.
      Study results indicated that earlier intervention in selected high-risk
      prethreshold eyes results in improved vision in premature infants with ROP.

PMID- 15157732
TI  - Samples of exact k-stage group sequential designs for Phase II and Pilot studies.
AB  - That the test of H(0): p=p(0) versus H(1): p>p(0) can be based on a binomially
      distributed random variable is widely known among users of statistical methods.
      What is not generally known is that under certain very general conditions, it is
      possible to find an exact k-stage group sequential test whose total sample size
      is bounded above by the sample size for the single stage binomial test. That is,
      it is possible to find k-stage tests for detecting H(1) for which the sum of the
      sample sizes at each of the stages is bounded above by the sample size for the
      standard binomial test. This result is somewhat remarkable since the total sample
      size under the group sequential test setting can be strictly less than the sample
      size for the uniformly most powerful (UMP) one-stage binomial test. In other
      words, exact group sequential tests cannot only save the average sample size but
      can also save the maximum sample size when they are compared to the standard
      binomial test. In this paper, implications of existing theory are explored and a
      web application written by the authors is presented. No new theory is
      established. Applications are described and methods are demonstrated that use the
      web application to rapidly create efficient designs for Phase II and Pilot
      studies that put a minimum number of patients at risk and that facilitate the
      rapid progression through a scientific research agenda. While couched here in the
      context of clinical trials, the results may be used in any field of inquiry where
      inferences are made based on the size of a binomial random variable.

PMID- 15157733
TI  - Structure and function of poly(A) binding proteins.
AB  - Poly (A) tails are found at the 3' ends of almost all eukaryotic mRNAs. They are
      bound by two different poly (A) binding proteins, PABPC in the cytoplasm and
      PABPN1 in the nucleus. PABPC functions in the initiation of translation and in
      the regulation of mRNA decay. In both functions, an interaction with the m7G cap
      at the 5' end of the message plays an important role. PABPN1 is involved in the
      synthesis of poly (A) tails, increasing the processivity of poly (A) polymerase
      and contributing to defining the length of a newly synthesized poly (A) tail.

PMID- 15157735
TI  - Polymorphisms of the porcine androgen receptor gene affecting its amino acid
      sequence and expression level.
AB  - Diverse physiological effects of the androgen receptor (AR), a nuclear
      transcription factor, and its mapping position within a quantitative trait loci
      (QTL) region on chromosome X propose it as an interesting candidate gene for pig
      reproduction and performance. Therefore, the aims of this study were isolation of
      the gene and detection of polymorphisms as a tool for association study and
      analysis of functional properties of the porcine AR. The mRNA and promoter
      sequences were obtained and screened for polymorphisms. Based on comparative
      sequencing, eight single nucleotide polymorphisms (SNPs), TG- and T
      insertion/deletetion polymorphisms (INDELs) upstream transcription initiation
      sites, three SNPs in the 5'-untranslated region (UTR), one microsatellite
      (CCTTT)n in the intron of 5'-UTR, and a CAG-INDEL in exon 1 were detected. Two
      haplotypes originated from Duroc and Berlin Miniature Pig were segregating in the
      DUMI-F2 resource population. Characterization of the porcine AR promoter showed
      two conserved transcription start sites, a consensus sequence of GC-box and a
      homopurine/homopyrimidine stretch at similar locations compared to the human, rat
      and mouse as well as sequences similar to androgen response elements (ARE). The
      AR mRNA expression levels determined by real-time RT-PCR in various tissues of
      female pigs were high in ovary (100%) and adrenal gland (83.9% relative to
      ovary), moderate in uterus (61.6%) and liver (47.4%), and low in pituitary gland
      (1.3%) as well as in tonsil, muscle, mammary gland, leukocyte and jejunum (less
      than 1%). Detection of the AR mRNA transcripts in liver revealed that hemizygous
      males carrying the AR haplotype descended from Berlin Miniature pig had higher
      relative AR expressions than did those with the Duroc haplotype. Here we showed
      that the porcine AR is a highly polymorphic gene. Polymorphisms identified in the
      present study affect the predicted amino acid sequence as well as consensus
      transcription factor binding sites and are associated with the allele-specific
      differences of the AR mRNA transcript level in liver, reinforcing AR as a
      potential candidate gene for traits related to pig reproduction and performance.

PMID- 15157734
TI  - Characterization of a homologue of the Rel/NF-kappaB transcription factor from a
      beetle, Allomyrina dichotoma.
AB  - A cDNA encoding a Rel/NF-kappaB homologue was cloned from a beetle, Allomyrina
      dichotoma, by reverse transcriptase-polymerase chain reactions (RT-PCR) taking
      advantage of the conserved Rel homology domain (RHD) to synthesize primers. The
      Rel/NF-kappaB homologue was designated A. dichotoma (A.d.) Rel A. The amino acid
      sequence of the A.d. Rel A RHD was compared with those of insect RHDs. The result
      showed that it has 70% identity with Tribolium castaneum Dorsal, 66% with
      Drosophila melanogaster Dorsal, 61% with Anopheles gambiae Gambif1, and 55% with
      D. melanogaster Dif. A putative phosphorylation site in the RHD, RRPS, and two
      putative nuclear localization signals were conserved in A.d. Rel A. A recombinant
      fusion protein containing the A.d. Rel A RHD was confirmed to bind specifically
      to the NF-kappaB site of a gene encoding A.d. coleoptericin A, an antibacterial
      peptide from A. dichotoma. The activity of A.d. Rel A in modulating a gene
      construct of the A.d. coleoptericin A promoter-luciferase reporter by expressing
      the A.d. coleoptericin A cDNA in a Bombyx mori cell line was analyzed. The result
      showed that A.d. Rel A strongly activates the A.d. coleoptericin A gene
      construct, whereas A.d. Rel A failed to activate the gene construct containing
      the mutated NF-kappaB site, suggesting the importance of the interaction between
      the NF-kappaB site and A.d. Rel A in the signal transduction for gene expression
      of antibacterial peptides in A. dichotoma.

PMID- 15157736
TI  - Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of
      the rat placenta.
AB  - Metastin is encoded by a putative human metastasis suppressor gene KiSS-1, and is
      the cognate ligand of a G-protein-coupled receptor designated OT7T175. To study
      the physiological function(s) of metastin, we cloned rat and mouse KiSS-1 cDNAs
      both encoding 130-amino acid KiSS-1 proteins. Sequence analysis suggested that
      processing of the rat and mouse KiSS-1 proteins produces 52-amino-acid peptides,
      each with an amidated carboxyl terminal and with a single possible disulfide
      bond, corresponding to rat and mouse metastins. The carboxyl-terminal sequence of
      metastin, known to be essential for functional receptor interaction, was found to
      be highly conserved among humans and rodents. Real-time PCR analysis indicated
      that rat KiSS-1 mRNA showed the highest expression level in the cecum and colon.
      Since KiSS-1 mRNA and metastin are known to be abundant in human placenta, we
      further studied the localization of KiSS-1 and OT7T175 mRNAs in rat placenta by
      in situ hybridization. KiSS-1 and OT7T175 mRNAs were specifically detected in
      trophoblast giant cells at embryonic day 12.5, and the transcripts in the cells
      gradually decreased during placental maturation. These results suggest that
      metastin/OT7T175 signaling may participate in implantation of the mammalian
      embryo, placenta formation, and maintenance of pregnancy.

PMID- 15157737
TI  - Cloning and characterization of the promoter region of human focal adhesion
      kinase gene: nuclear factor kappa B and p53 binding sites.
AB  - Focal adhesion kinase (FAK) gene encodes focal adhesion kinase that localizes at
      contact points of cells with extracellular matrix. It was shown that FAK
      expression is increased in a variety of malignancies, both at early and advanced
      stages of tumorigenesis. To understand mechanisms of FAK gene expression and
      regulation, we cloned and characterized the 5' promoter region of the FAK gene.
      The 1.2-kb fragment with FAK promoter was placed upstream of the luciferase
      reporter gene in a pGL3-Basic vector and transfected into different cell lines.
      Endogenous high-FAK-expressing cell lines showed high levels of luciferase
      activity in contrast to low-FAK-expressing cells, indicating on transcriptional
      level of FAK regulation. Serial deletion constructs revealed that a approximately
      600 base pair region (-564 to +47) is required for the maximal FAK promoter
      activity. The 5'-flanking region of FAK is GC-rich and contains several potential
      transcription factor binding sites, including two NF-kappa B and p53 binding
      sites. Inhibition of NF-kappa B with NF-kappa B super-repressor decreased FAK
      luciferase activity. Induction with TNF-alpha increased luciferase activity
      confirming a role of NF-kappa B transcription factor in the FAK transcriptional
      activation. The binding of NF-kappa B and p53 transcription factors to the FAK
      promoter region was demonstrated by electrophoretic mobility shift assay (EMSA).
      Cotransfection of NF-kappa B and p53 plasmids with FAK promoter luciferase
      constructs demonstrate induction and inhibition, respectively, of FAK luciferase
      activity. The results provide a molecular basis for analysis of FAK
      transcriptional regulation.

PMID- 15157738
TI  - Genomic and phylogenetic footprinting at the epsilon-globin silencer region in
      intact human cells.
AB  - Chromatin structure at the silencer region of the epsilon-globin promoter was
      investigated using novel nitrogen mustards as probes of protein--DNA
      interactions. Sites of protection and enhancement that corresponded to known
      transcription factor binding sites were detected in both K562 and HeLa cells at
      this gene region. Protection was observed at several sites including the GATA
      1/YY1 motifs. Of particular interest was a large 155 bp footprint that was
      observed at the epsilon-globin gene silencer region of the promoter. This large
      footprint was consistent with the presence of a positioned nucleosome core in
      intact human cells at this silencer region. Additionally, the DNA sequence at the
      epsilon-globin silencer and promoter was compared for 11 mammalian species.
      Significant areas of conservation were found that correlated with known
      transcription factor binding motifs. This phylogenetic footprinting analysis was
      compared to the genomic footprinting data at the epsilon-globin silencer region.

PMID- 15157740
TI  - Molecular cloning and characterization of three adult rat beta-globin gene
      promoters.
AB  - We analyzed the promoter regions of the adult rat beta (IIbeta, IIIbeta, and
      0beta)-globin genes. The results indicated that (1) the activities of the minimal
      promoters of these three genes are proportional to the gene expression levels in
      vivo, and (2) erythroid-specific repressor regions are located immediately
      upstream of the minimal promoter sequences and are regulated by the same
      transcription factor.

PMID- 15157739
TI  - Retinoids increase alpha-1 acid glycoprotein expression at the transcriptional
      level through two distinct DR1 retinoic acid responsive elements.
AB  - In the present study, we analyzed the influence of retinoic acids on the
      expression of alpha-1 acid glycoprotein (AGP). We show that in rat primary
      hepatocytes, 9-cis retinoic acid and all-trans retinoic acid increase AGP gene
      expression at the transcriptional level. Transient transfections of rat primary
      hepatocytes with a reporter construct driven by the rat AGP gene promoter
      indicated that retinoids regulate AGP gene expression via the -763/-138 region of
      the AGP promoter. Furthermore, cotransfection experiments with retinoic acid
      receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha) expression
      vectors in NIH3T3 cells demonstrated that both RXRalpha/RXRalpha homodimer and
      RXRalpha/RARalpha heterodimer are competent for ligand-induced transactivation of
      the AGP promoter. Unilateral deletion and site-directed mutagenesis identified
      two retinoic-acid responsive elements (RARE), RARE-I and RARE-II, which
      interestingly correspond to a direct repeat of two TGACCT-related hexanucleotides
      separated by a single bp only (DR1-type response element). Cotransfection assays
      showed that RXRalpha and RARalpha activate AGP gene transcription through these
      two elements either as a homodimer (RXRalpha/RXRalpha) or as a heterodimer
      (RXRalpha/RARalpha). The RXRalpha/RXRalpha homodimer acts most efficiently
      through the RARE-I response element to promote AGP transactivation, whereas the
      RXRalpha/RARalpha heterodimer mediates transactivation better via the RARE-II
      responsive element.

PMID- 15157741
TI  - Role of specificity protein-1, PPARgamma, and pituitary protein transcription
      factor-1 in transcriptional regulation of the murine CORS-26 promoter.
AB  - The collagenous repeat-containing sequence of 26-kDa protein (CORS-26) was
      recently described as a new gene that is induced during adipocyte
      differentiation. Since the transcription factors specificity protein-1 (SP-1) and
      PPARgamma have been demonstrated to modulate transcriptional activation of
      adipocytic genes, we investigated the putative role of SP-1 and PPARgamma in the
      regulation of the murine CORS-26 promoter. Computer-based sequence analysis
      revealed two putative SP-1 binding sites and binding sites for PPARgamma and Pit
      1 within the TATA-box containing promoter. Electrophoretic mobility shift assays
      (EMSA) with nuclear extracts from 3T3-L1 adipocytes and appropriate promoter
      fragments demonstrated that SP-1 binds specifically to both SP-1 binding sites.
      Specificity was demonstrated by (i) the appearance of supershift bands, (ii)
      competition experiments and, (iii) by using oligonucleotides carrying mutated SP
      1 binding sites. Functional promoter activity was analyzed by Luciferase reporter
      gene assays and SP-1 was shown to exert inhibitory effects on the transcriptional
      activation of the murine CORS-26 gene. Additionally, specific binding activity of
      PPARgamma and Pit-1 to the CORS-26 promoter was demonstrated. Taken together, the
      present data demonstrate the functionality of the proximal murine CORS-26
      promoter, which is regulated specifically by two SP-1 binding sites via SP-3
      independent repressive effects of SP-1 on transcriptional activation. Pit-1 and
      PPARgamma can bind specifically to the promoter and might play an additive
      functional role in gene regulation of murine CORS-26.

PMID- 15157742
TI  - Chicken ovalbumin upstream promoter-transcription factor I represses the
      transcriptional activity of the human muscle glycogen phosphorylase promoter in
      C2C12 cells.
AB  - The responsiveness of the 1.13 kb proximal human muscle glycogen phosphorylase
      (MGP) gene promoter to the chicken ovalbumin upstream promoter-transcription
      factor (COUP-TF) repressor, known to be ablated during muscle cell
      differentiation, was examined. Constitutive expression of COUP-TFI repressed the
      activity of the promoter in C2C12 muscle cells and sequential deletion analysis
      mapped the sensitive region between nucleotides -362 and -185, which included a
      putative consensus COUP-TF binding half-site at -198/-193. Mutation of this site
      abolished transcriptional response to COUP-TFI of the -362 construct. A -209/-180
      probe bound in vitro to COUP-TFI and to protein extracts from proliferating but
      not fusing myoblasts. Thus, COUP-TF may be involved in repression of the human
      MGP gene promoter at the myoblast stage.

PMID- 15157743
TI  - Structural organization of the murine microsomal glutathione S-transferase gene
      (MGST1) from the 129/SvJ strain: identification of the promoter region and a
      comprehensive examination of tissue expression.
AB  - The structure and regulation of the murine microsomal glutathione transferase
      gene (MGST1) from the 129/SvJ strain is described and demonstrates considerable
      difference in nucleotide sequence and consequently in restriction enzyme sites as
      compared to other mouse strains. A comparison of the amino acid sequence for
      MGST1 revealed one difference in exon 2 between the 129/SvJ strain (arginine at
      position 5) and the sequence previously reported for the Balb/c strain (lysine).
      The promoter region immediately upstream of the dominant first exon is
      functional, transcriptionally responds to oxidative stress, and is highly
      homologous to the human region. Oxidative stress also induced the production of
      endogenous MGST1 mRNA. The tissue-specific expression of MGST1 mRNA was studied,
      and as anticipated, was indeed highest in liver. There was, however, marked mRNA
      expression in several tissues not previously studied including smooth muscle,
      epidymus, ovaries, and endocrine glands in which the expression of various
      peroxidases is also very high (salivary and thyroid). Overall, there was a good
      agreement between the mRNA content detected and previous reports of MGST1
      activity with the exception of brain tissue.

PMID- 15157744
TI  - Isolation and characterization of two nuclear genes encoding glutathione and
      thioredoxin reductases from the yeast Kluyveromyces lactis.
AB  - Response to oxidative stress has been hitherto scarcely studied in the
      respiratory yeast Kluyveromyces lactis. The genes coding for reductases of
      glutathione and thioredoxin, KlGLR1 and KlTRR1, respectively, have been cloned
      and characterized in this work. H(2)O(2) treatment increased transcription and
      enzyme activity of KlTRR1 but not of KlGLR1, suggesting a different situation
      from that reported for the fermentative yeast Saccharomyces cerevisiae. A
      consensus for Yap1p binding is functional in the KlTRR1 promoter.

PMID- 15157745
TI  - Effect of repeat exposure on neuroendocrine and symptom responses to
      pentagastrin.
AB  - The cholecystokinin (CCK-B) agonist pentagastrin stimulates dose-dependent
      release of adrenocorticotropin (ACTH) and cortisol in humans, likely via direct
      pharmacological action at pituitary CCK-B receptors. Pentagastrin also produces
      side effects, however, which may be experienced as novel or anxiety arousing and
      could contribute to ACTH release. Available data suggest that pentagastrin's
      activation of the hypothalamic-pituitary-adrenal (HPA) axis is unrelated to
      anxiety symptoms themselves, but novelty effects have not been examined in this
      model and do strongly activate this system in animals. To further explore the
      impact of novelty and anxiety symptoms on HPA responses, pentagastrin was
      administered twice to 12 subjects (six male, six female) under single-blind
      conditions. Repeat pentagastrin injection was associated with a slight
      habituation in the magnitude of symptom and HPA axis responses, but robust HPA
      and symptom responses were seen following both injections. No relationships were
      found between anxiety symptoms and HPA activity and the modest symptomatic and
      neuroendocrine habituation appeared to occur independently. Pentagastrin may
      release ACTH and cortisol through direct pharmacological action, perhaps enhanced
      on first exposure by psychologically mediated novelty effects. Novelty, per se,
      is not likely the primary mediator of the HPA response. This model may be useful
      for further study of cognitive-emotional modulators of HPA axis activity.

PMID- 15157746
TI  - Relationship between baseline cortisol, social functioning and depression: a
      mediation analysis.
AB  - Both elevated cortisol secretion and low social support have been commonly found
      in depressed patients, but their respective roles in depression remain unclear.
      In fact, it may not be a lack of social support but a failure to obtain it that
      is important. The present study used mediation analysis to study the
      interrelationships among cortisol, social functioning and depression. Sixty
      healthy volunteers were recruited from the community. Depression and social
      functioning were measured by the Beck Depression Inventory and the Social
      Adaptation Self-evaluation Scale, respectively. Salivary samples were collected
      to measure the cortisol. Using mediation analysis, it was found that elevated
      cortisol secretion was a vulnerability factor for low social functioning, leading
      to higher depression scores. Hypercortisolaemia may be a predisposing factor and
      may interact with a low level of social functioning leading to depression.

PMID- 15157747
TI  - Sensory gating deficits during the mid-latency phase of information processing in
      medicated schizophrenia patients.
AB  - Sensory gating during preattentive phases of information processing has been
      extensively examined. Sensory gating processes that occur during subsequent
      phases of information processing have not been fully examined. The relationship
      between P50 sensory gating and schizophrenia symptoms remains underspecified and
      the clinical correlates of N100 and P200 gating are yet to be examined. Sensory
      gating indices derived from the mid-latency auditory evoked responses during
      preattentive (P50) and attentive (N100, P200) phases of information processing
      were collected from schizophrenia patients who were stable and mainly being
      treated with atypical antipsychotic medications (n=23) and age- and gender
      matched healthy control subjects (n=23). Schizophrenia patients had demonstrable
      habituation or sensory gating difficulties throughout the mid-latency range of
      information processing. Moreover, we found no correlations between P50-derived
      sensory gating indices and the amplitude or latency of the more attention-related
      P300 evoked response. A number of N100 and P200 gating measures correlated with
      P300 variables. Finally, we found no correlations between sensory gating indices
      and schizophrenia symptoms clusters. These results suggest that sensory gating is
      a pervasive abnormality in schizophrenia patients that is not limited to the
      preattentive phase of information processing. Furthermore, the data suggest that
      N100 and P200 gating indices may influence subsequent information processing.

PMID- 15157748
TI  - Longitudinal assessment of psychopathological domains over late-stage
      schizophrenia in relation to duration of initially untreated psychosis: 3-year
      prospective study in a long-term inpatient population.
AB  - There remains uncertainty regarding any progressive nature of psychopathology and
      cognitive dysfunction in late-stage schizophrenia, and whether duration of
      initially untreated psychosis (DUP) might be associated with such 'progression'.
      This study examines longitudinally, over 3 years, the psychopathology and
      neuropsychology in 82 inpatients with DSM-IV schizophrenia, many of whom were
      admitted in the pre-neuroleptic era. Increase in executive dysfunction exceeded
      that in general cognitive impairment. Positive but not negative symptom severity
      decreased modestly; the primary predictor of negative symptom severity was DUP.
      On index assessment, psychopathology evidenced a three-factor structure; at
      follow-up, psychomotor poverty evidenced greater prominence and cohesion, and was
      on both occasions predicted primarily by DUP, while reality distortion was
      altered and disorganisation disassembled into alternative elements. It would
      appear that as years of chronic, refractory illness accrue, psychomotor poverty
      becomes more sharply delineated and dominant within the overall structure of
      psychopathology, and its prominence is predicted enduringly by DUP.

PMID- 15157749
TI  - Cognitive functioning in adolescents with schizophrenia spectrum disorders.
AB  - In contrast to studies of cognitive functioning in adults with schizophrenia,
      there has been a relative paucity of studies assessing adolescents with
      schizophrenia. We investigated cognitive functioning in 22 adolescents with
      schizophrenia spectrum disorders compared with 30 healthy adolescents. The
      patient group demonstrated impaired performance on all of the functions
      investigated except sustained attention. Against the background of this broad
      impairment, executive function and psychomotor speed were the most impaired,
      sustained attention was spared, while preattentional processing, early visual
      information processing, visual long-term memory, auditory short-term memory and
      working memory emerged as relative deficits. The study shows that adolescents
      with schizophrenia spectrum disorders demonstrate a similar pattern of cognitive
      functioning to adults in all areas, except sustained attention.

PMID- 15157750
TI  - Maintaining and updating semantic context in schizophrenia: an investigation of
      the effects of multiple remote primes.
AB  - Conflicting findings regarding the ability of people with schizophrenia to
      maintain and update semantic contexts have been due, arguably, to vagaries within
      the experimental design employed (e.g. whether strongly or remotely associated
      prime-target pairs have been used, what delay between the prime and the target
      was employed, and what proportion of related prime-target pairs appeared) or to
      characteristics of the participant cohort (e.g. medication status, chronicity of
      illness). The aim of the present study was to examine how people with
      schizophrenia maintain and update contextual information over an extended
      temporal window by using multiple primes that were either remotely associated or
      unrelated to the target. Fourteen participants with schizophrenia and 12 healthy
      matched controls were compared across two stimulus onset asynchronies (SOAs)
      (short and long) and two relatedness proportions (RP) (high and low) in a crossed
      design. Analysis of variance statistics revealed significant two- and three-way
      interactions between Group and SOA, Group and Condition, SOA and RP, and Group,
      SOA and RP. The participants with schizophrenia showed evidence of enhanced
      remote priming at the short SOA and low RP, combined with a reduction in the time
      course over which context could be maintained. There was some sensitivity to
      biasing contextual information at the short SOA, although the mechanism over
      which context served to update information appeared to be different from that in
      the controls. The participants with schizophrenia showed marked performance
      decrements at the long SOA (both low and high RP). Indices of remote priming at
      the short (but not the long) SOA correlated with both clinical ratings of thought
      disorder and with increasing length of illness. The results support and extend
      the hypothesis that schizophrenia is associated with concurrent increases in
      tonic dopamine activity and decreases in phasic dopamine activity.

PMID- 15157751
TI  - Effects of depressive symptoms and anxiety on hemostatic responses to acute
      mental stress and recovery in the elderly.
AB  - Depression and anxiety are prospectively associated with cardiac morbidity and
      mortality. Increased clotting diathesis may mediate this link. We hypothesized
      that there would be an association between mood and hemostatic changes that occur
      during and following recovery from acute mental stress. Forty-eight community
      dwelling elderly subjects underwent a laboratory speech stressor task. Plasma von
      Willebrand factor (vWF), thrombin/antithrombin III (TAT) complexes, D-dimer,
      tissue-type plasminogen activator (t-PA), and type I plasminogen activator
      inhibitor (PAI-1) were measured at rest, after conclusion of the speech, and 14
      min afterwards (recovery). Mood was assessed with the Hamilton Rating Scales for
      Depression (Ham-D) and Anxiety (Ham-A). Mental stress elicited a hypercoagulable
      state as evidenced by increases in TAT and D-dimer, and by a decrease in t-PA.
      Overall, hypercoagulability had increased after recovery. Ham-D scores and Ham-A
      scores correlated with increases in D-dimer over the testing interval (i.e. area
      under the curve). Ham-A (but not Ham-D) uniquely explained 8% and 17% of the
      variance in resting D-dimer and D-dimer area under the curve, respectively. The
      independent association of anxiety symptoms with resting and stress-induced
      fibrin formation (D-dimer) may be a mechanism linking mood with cardiovascular
      disease risk in the elderly.

PMID- 15157752
TI  - Neuropsychological function in college students with and without posttraumatic
      stress disorder.
AB  - Previous research on the neuropsychology of posttraumatic stress disorder (PTSD)
      has identified several neurocognitive deficits that co-occur with the disorder.
      However, it remains unclear whether these deficits are due to trauma exposure,
      PTSD symptomatology or psychiatric/substance abuse comorbidity. We examined
      trauma exposure, PTSD symptoms and neuropsychological performance in 235
      undergraduate students, i.e. a non-clinical sample. The sample comprised 146
      subjects with trauma exposure (38 with current PTSD and 108 without lifetime
      PTSD) and 89 no-trauma comparison (NC) subjects who were administered tests of
      attention, working memory, psychomotor speed, word generation and executive
      functioning. Relationships of neuropsychological functioning to measures of
      psychiatric symptoms and substance abuse were examined. Current PTSD (PTSD+),
      trauma-exposed without PTSD (PTSD-) and NC subjects did not differ significantly
      on the vast majority of neuropsychological tests. There were very few significant
      associations between neuropsychological performance and clinical variables, and
      those that were statistically significant were small in magnitude. The striking
      lack of differences in neuropsychological performance between the three groups
      suggests that college students with trauma exposure, regardless of the presence
      of PTSD symptoms, may be cognitively resilient. Neuropsychological impairment may
      not be an invariant feature of PTSD, but when it is present, it may be associated
      with poorer functional outcomes.

PMID- 15157753
TI  - Coping strategies and behavioral/emotional problems among Chinese adolescents.
AB  - This study was carried out to describe strategies used to cope with stress and to
      explore the association between coping strategies and behavioral/emotional
      problems in a community sample of adolescents from Mainland China. Participants
      completed a self-administered questionnaire incorporating the Chinese Trait
      Coping Style Questionnaire, the Chinese version of the Youth Self-Report of Child
      Behavior Checklist, and a number of demographic questions. Results indicated that
      Chinese adolescents often used multiple coping strategies when faced with stress.
      Principal factor analysis followed by oblique rotation revealed two dimensions of
      coping strategies in Chinese adolescents: active coping and avoidant coping. A
      series of logistic regression analyses showed that avoidant coping was
      significantly associated with increased risk for internalizing and externalizing
      problems, but active coping was associated with reduced risk, after adjustment
      for child's age and sex and father's occupation. These findings provide evidence
      of the association between coping and mental health problems in Chinese
      adolescents.

PMID- 15157754
TI  - Anxiety and somatic symptoms as predictors of treatment-related adverse events in
      major depressive disorder.
AB  - The purpose of this study was to examine the relationship between the degree of
      anxiety or somatic symptoms present before treatment with the subsequent
      diagnosis of treatment-related adverse events (TRAEs) in patients with major
      depressive disorder (MDD) enrolled in an 8-week open trial of fluoxetine (20 mg).
      Baseline symptom questionnaires (SQ) were completed by 170 MDD patients enrolled
      in the trial. We then tested whether pre-treatment scores for anxiety and somatic
      symptoms predicted (1) whether patients were subsequently diagnosed with TRAEs;
      (2) whether they were subsequently diagnosed with moderate or severe TRAEs; or
      (3) whether a greater number of TRAEs were diagnosed during the trial. We found
      that depressed patients who presented with prominent somatic symptoms were
      significantly more likely to report at least one moderate or severe side effect
      during the course of treatment, but not more likely to report a greater number of
      side effects. Pre-treatment anxiety was not related to the development of side
      effects.

PMID- 15157755
TI  - Strategy choices in simple and complex addition: Contributions of working memory
      and counting knowledge for children with mathematical disability.
AB  - Groups of first-grade (mean age = 82 months), third-grade (mean age = 107
      months), and fifth-grade (mean age = 131 months) children with a learning
      disability in mathematics (MD, n = 58) and their normally achieving peers (n =
      91) were administered tasks that assessed their knowledge of counting principles,
      working memory, and the strategies used to solve simple (4+3) and complex (16+8)
      addition problems. In all grades, the children with MD showed a working memory
      deficit, and in first grade, the children with MD used less sophisticated
      strategies and committed more errors while solving simple and complex addition
      problems. The group differences in strategy usage and accuracy were related, in
      part, to the group difference in working memory and to group and individual
      differences in counting knowledge. Across grade-level and group, the switch from
      simple to complex addition problems resulted in a shift in the mix of problem
      solving strategies. Individual differences in the strategy mix and in the
      strategy shift were related, in part, to individual differences in working memory
      capacity and counting knowledge.

PMID- 15157756
TI  - Categorical perception of speech stimuli in children at risk for reading
      difficulty.
AB  - Children determined to be at risk (n = 24) or not at risk (n = 13) for reading
      difficulty listened to tokens from a voice onset time (VOT) (/ga/-/ka/) or tone
      series played in a continuous unbroken rhythm. Changes between tokens occurred at
      random intervals and children were asked to press a button as soon as they
      detected a change. For the VOT series, at-risk children were less sensitive than
      not-at-risk children to changes between tokens that crossed the phonetic
      boundary. Maps of group stimulus space produced using multidimensional scaling of
      reaction times for the VOT series indicated that at-risk children may attend less
      to the phonological information available in the speech stimuli and more to
      subtle acoustic differences between phonetically similar stimuli than not-at-risk
      children. Better phonological processing was associated with greater sensitivity
      to changes between VOT tokens that crossed the phonetic boundary and greater
      relative weighting of the phonological compared to the acoustic dimension across
      both groups.

PMID- 15157757
TI  - More evidence on size modification in spatial axes systems of varying complexity.
AB  - Pictorial space can be conceptualized as aggregate space (where figures compete
      for limited available space) or as axial space (where space is infinite and
      exists independently of figures). That these two kinds of space concepts follow a
      developmental sequence was tested by investigating size regulation mechanisms in
      7- to 12-year-old children's figure drawings. An earlier longitudinal study had
      shown that the more figures were drawn and the more complex the spatial axes
      system, the smaller the figures. Two studies confirmed that object-driven size
      reduction was the size regulation mechanism in younger children, whereas axes
      driven size reduction was the only factor regulating figure size in 12-year-old
      children. Size reduction occurred in a gradual fashion in younger children,
      whereas size reduction was more pronounced in crossed axes systems in older
      children. In addition, 7-year-old children showed a dynamic and fluid interaction
      between internal and external task demands for size regulation.

PMID- 15157758
TI  - The development of young children's memory strategies: First findings from the
      Wurzburg Longitudinal Memory Study.
AB  - This article reports the first findings of the Wurzburg Longitudinal Memory
      Study, which focuses on children's verbal memory development, particularly the
      acquisition of memory strategies. At the beginning of the study, 100 kindergarten
      children (mean age 6 1/2 years) were tested on various memory measures, including
      sort-recall, text recall, short-term memory capacity, and metamemory. Assessments
      were repeated twice, with adjacent measurement points separated by 6-month time
      intervals. One major goal of the initial phase of the study concerned the
      exploration of the utilization deficiency phenomenon, which refers to the fact
      that young children who spontaneously use a memory strategy for the first time do
      not experience immediate memory benefits. Results obtained for the sort-recall
      task showed that, among those children who acquired a sorting strategy between
      Times 1 and 2, only a small proportion experienced the utilization deficiency
      problem. Additional analyses demonstrated that these few children also performed
      more poorly on the short-term memory tasks and the text recall measure when
      compared with the groups of efficient strategy users, suggesting that utilization
      deficiency is accompanied by a more general memory capacity problem. Overall, the
      findings revealed enormous variability in the early acquisition of memory
      strategies, indicating that the utilization deficiency phenomenon might not be as
      frequent as is assumed in the relevant literature.

PMID- 15157759
TI  - Complete development of Cryptosporidium parvum in host cell-free culture.
AB  - The present study describes the complete in vitro development of Cryptosporidium
      parvum (cattle genotype) in RPMI-1640 maintenance medium devoid of host cells.
      This represents the first report in which Cryptosporidium is shown to multiply,
      develop and complete its life cycle without the need for host cells. Furthermore,
      cultivation of Cryptosporidium in diphasic medium consisting of a coagulated new
      born calf serum base overlaid with maintenance medium greatly increased the total
      number of Cryptosporidium stages. Type I and II meronts were detected giving rise
      to two morphologically different merozoites. Type I meronts, which appear as
      grape-like clusters as early as 48 h post culture inoculation, release
      merozoites, which are actively motile, and circular to oval in shape. Type II
      meronts group in a rosette-like pattern and could not be detected until day 3 of
      culturing. Most of the merozoites released from type II meronts are generally
      spindle-shaped with pointed ends, while others are rounded or pleomorphic. In
      contrast to type I, merozoites from type II meronts are less active and larger in
      size. Sexual stages (micro and macrogamonts) were observed within 6-7 days of
      culturing. Microgamonts were darker than macrogamonts, with developing
      microgametes, which could be seen accumulating at the periphery. Macrogamonts
      have a characteristic peripheral nucleus and smooth outer surface. Oocysts at
      different levels of sporulation were seen 8 days post culture inoculation.
      Cultures were terminated after 4 months when the C. parvum life cycle was still
      being perpetuated with the presence of large numbers of excysting and intact
      oocysts. Culture-derived oocysts obtained after 46 days p.i. were infective to 7-
      to 8-day-old ARC/Swiss mice. The impact of C. parvum developing in cell-free
      culture is very significant and will facilitate many aspects of Cryptosporidium
      research.

PMID- 15157760
TI  - Trypanosoma cruzi: long-term sub-cultures in two different culture media do not
      confirm the existence of highly versatile multilocus genotypes.
AB  - Trypanosoma cruzi Y reference strain is found in many laboratories under at least
      two highly distinct genotypes, A and B corresponding to the 'discrete typing
      units' T. cruzi IIb and T. cruzi IId, respectively. Previous work has reported
      reversible switches between these genotypes according to the culture media used
      in the experiments: genotype A would be associated with blood-enriched culture
      media, while genotype B would be associated with blood-free culture media. We
      tried to reproduce this observation, but used a different cloning method of
      individual organisms. Our cloning was verified visually under the microscope,
      while the previous studies relied on a cloning by dilution only. The subclones so
      obtained were submitted to long-term exposure to both media, and no change was
      observed in isoenzyme and random amplified polymorphic DNA genotypes. The
      discrepancy is probably explained by the cloning method: clones obtained from the
      previous method (dilution and plating) could come from several parasite cells
      while only one cell generates a clone when micro-manipulation is used.

PMID- 15157761
TI  - Proteinase inhibitors TPCK and TLCK prevent Entamoeba histolytica induced
      disturbance of tight junctions and microvilli in enteric cell layers in vitro.
AB  - Tight junctions and microvilli constitute an anti-invasive barrier at the luminal
      side of enteric cell layers. Both subcellular structures are disrupted following
      adhesion of Entamoeba histolytica trophozoites to enteric cell layers in vitro.
      It was our aim to analyse the molecular mechanism underlying this disruption.
      Therefore, we cocultured enteric T84 cell layers established on filter inserts
      with E. histolytica trophozoites and tested various modulators of enteric
      molecules, involved in the functional regulation of tight junctions, as well as
      inhibitors of trophozoite virulence factors on their capacity to maintain the
      transepithelial electrical resistance. Pretreatment of trophozoites with the
      proteinase inhibitor N-Tosyl-Phenylalanine chloromethyl ketone or N-Tosyl-l
      Lysine chloromethyl ketone prevented the decrease in transepithelial electrical
      resistance whereas none of the modulators used to pretreat enterocytes were
      successful. Moreover, zymography and Western blot analysis revealed that both N
      Tosyl-Phenylalanine chloromethyl ketone and N-Tosyl-l-Lysine chloromethyl ketone
      inhibited E. histolytica cysteine proteinases and prevented proteolysis of tight
      junction molecules ZO-1 and ZO-2 and of villin, the major actin bundling molecule
      in microvilli. Immunocytochemistry with an antibody against ezrin, an actin
      binding molecule in microvilli, and phase contrast microscopy demonstrated that
      pretreatment of trophozoites with N-Tosyl-Phenylalanine chloromethyl ketone or N
      Tosyl-l-Lysine chloromethyl ketone also prevented disturbance of microvilli and
      destruction of Caco-2 enteric cell layers in cocultures. Taken together, our
      results indicate that trophozoites use their proteinases to overcome microvilli
      and tight junction barriers during the invasion of enteric cell layers, that
      these phenomena could be prevented by pretreatment of trophozoites with N-Tosyl
      Phenylalanine chloromethyl ketone or N-Tosyl-l-Lysine chloromethyl ketone, and
      that such pretreatment disabled trophozoites to destroy enteric cell layers in
      vitro.

PMID- 15157762
TI  - A real-time PCR assay for quantifying Plasmodium falciparum infections in the
      mosquito vector.
AB  - Transmission-blocking vaccines prevent the development of Plasmodium parasite
      within the mosquito vector, thereby thwarting the spread of malaria through a
      community. The gold standard for determining the efficacy of a transmission
      blocking vaccine is the standard membrane feeding assay. This assay requires the
      dissection of mosquitoes and microscopic counting of oocysts present on the
      mosquito mid-gut, typically at 7-10 days p.i. Here we describe a real-time
      quantitative PCR assay that is rapid, target-specific and robust, with a
      sensitive detection threshold and which may be employed earlier p.i. than the
      standard membrane feeding assay and is applicable to preserved material. The real
      time PCR assay utilises the LightCycler platform and SYBR Green I detection
      system to amplify 180 bp of the asexual form of the Plasmodium falciparum rRNA
      gene. It has a quantitative range of greater than four orders of magnitude and a
      detection threshold of 10 parasites. Validation experiments using a monoclonal
      antibody of known blocking activity revealed the real-time PCR assay to give
      equivalent results to the standard membrane feeding assay. In addition, the PCR
      assay can establish the effect of such a monoclonal antibody on the parasites'
      development within the oocyst and on the sporozoite (the transmissible stage)
      yield, providing a more pertinent assessment of transmission blocking activity
      than is possible by the standard membrane feeding assay. This assay may also be
      employed to monitor the sporogonic development of P. falciparum parasites within
      the mosquito vector.

PMID- 15157763
TI  - A Leishmania donovani gene that confers accelerated recovery from stationary
      phase growth arrest.
AB  - We have isolated a gene, LdGF1, from the protozoan parasite Leishmania donovani.
      Overexpression of this gene confers a strong selective advantage in liquid
      culture after stationary phase growth arrest. We could show that recombinant L.
      donovani or Leishmania major, when overexpressing LdGF1, recover faster from a
      stationary phase growth arrest than control parasite strains. While no advantage
      of LdGF1 overexpression could be observed in log phase cultures or after a
      hydroxyurea-induced S-phase growth arrest, recovery from a cell cycle arrest due
      to serum deprivation was faster in LdGF1-overexpressing strains. This was found
      to be due to an accelerated release from a G(1) cell cycle arrest. By contrast,
      in a BALB/c mouse infection system, overexpression of LdGF1 in L. major resulted
      in reduced virulence. We conclude that increased levels of LdGF1 are beneficiary
      during recovery from G(1) cell cycle arrest, but pose a disadvantage inside a
      mammalian host. These results are discussed in the context of the observed loss
      of virulence during in vitro passage of Leishmania parasites.

PMID- 15157764
TI  - Optimal parasite infection strategies: a state-dependent approach.
AB  - Many macroparasites spend a crucial phase of their life-cycle as free-living
      infective stages. Despite their importance, however, little theoretical work has
      considered how evolution may shape the behaviour of these stages. Here, we
      develop what we believe to be the first stochastic dynamic programming model of
      parasite life-history strategies to investigate how a trade-off between resource
      depletion and host encounter rate may shape the optimal infection strategy of a
      macroparasite. The optimal strategy depends strongly on the probability of host
      contact and, depending on the relative costs and benefits, macroparasites should
      adopt either a passive 'ambushing' (sit-and-wait) strategy, an active 'cruising'
      strategy or a mixed strategy with an initial cruising phase, followed by a switch
      to ambushing when energy reserves fall to a threshold level. Under no
      circumstances does the model predict ambush-then-cruise. We use our model to help
      interpret previously published data on entomopathogenic nematode foraging
      behaviour, showing how this framework could facilitate our understanding of
      macroparasite behaviour during this key stage of the life-cycle.

PMID- 15157766
TI  - A comparison of the immunosuppressive effects of salivary gland extracts from two
      laboratory strains of Boophilus microplus.
AB  - This study addresses three questions related to the immune response of cattle to
      tick salivary gland extracts. Firstly, is there a difference in the inhibition of
      proliferation of Concanavalin A (ConA) stimulated bovine lymphocytes induced by
      salivary gland extracts of the N and Y strains of Boophilus microplus? Second, is
      there a difference in the development rate of the Y and N tick strains? Third,
      does the host affect the inhibitory effect of salivary gland extract on the
      proliferation of ConA stimulated lymphocytes from the two tick strains? Salivary
      gland extract of the Y strain inhibited in vitro proliferation of lymphocytes
      stimulated by ConA significantly more than that of the N strain, when each strain
      was raised on different animals. A difference in the development rate was
      observed between the tick strains when raised on the same animal, with female
      ticks of the Y strain developing faster and reaching a greater fully engorged
      weight than ticks of the N strain. The difference in their rate of development
      did not appear to contribute to a difference in inhibitory effects of the
      salivary gland extracts and there was no difference between the inhibitory
      effects of salivary gland extracts from both strains. However, when Y strain
      ticks were raised on different animals, there was a significant difference in the
      inhibition of lymphocyte proliferation between the two salivary gland extracts.
      Therefore, it was concluded that there is no difference between the inhibitory
      effects of the two tick strains and that the host has an influence on salivary
      gland extract composition of B. microplus and its inhibitive properties.

PMID- 15157765
TI  - Molecular characterisation of five trypsin-like peptidase transcripts from the
      salmon louse (Lepeophtheirus salmonis) intestine.
AB  - Four novel trypsin-like S1A peptidase transcripts (LsTryp2-5) from the marine
      parasitic copepod Lepeophtheirus salmonis were characterised based on analyses of
      1918 expressed sequence tags from two adult female libraries. In addition, one
      previously described salmon louse trypsin, LsTryp1, has been further
      characterised. The five peptidases possessed all residues typically found in
      trypsins in correct sequence contexts. Interestingly, two cysteine residues,
      possibly involved in a disulphide bridge not previously reported in trypsins are
      conserved in all louse trypsin sequences. Phylogenetic analyses showed that the
      five louse peptidases form a monophyletic group with other crustacean trypsins
      (Brachyurin Ts). Quantitative PCR analyses demonstrated increased transcript
      levels from planktonic to early host-attached stages and from preadult to
      sexually mature adult stages. Furthermore, sex-specific differences in
      transcription regulation were found. In situ hybridisation demonstrated that all
      five trypsin-like peptidases are transcribed throughout the undifferentiated
      midgut, indicating a digestive function. The sequence characteristics,
      histological localisation and transcript regulation suggest that LsTryp1-4 encode
      typical digestive trypsins. LsTryp5, however, showed some sequence and regulatory
      peculiarities that rendered its function less clear. Our findings support earlier
      suggestions for the function of the midgut cells and suggest the existence of an
      additional undifferentiated cell-type.

PMID- 15157767
TI  - Genetic epidemiology of Sarcoptes scabiei (Acari: Sarcoptidae) in northern
      Australia.
AB  - Utilising three hypervariable microsatellite markers we have previously shown
      that scabies mites on people are genetically distinct from those on dogs in
      sympatric populations in northern Australia. This had important ramifications on
      the formulation of public health control policies. In contrast phylogenetic
      analyses using mitochondrial markers on scabies mites infecting multiple animal
      hosts elsewhere in the world could not differentiate any genetic variation
      between mite haplotype and host species. Here we further analyse the intra
      specific relationship of Sarcoptes scabiei var. hominis with S. scabiei var.
      canis by using both mitochondrial DNA and an expanded nuclear microsatellite
      marker system. Phylogenetic studies using sequences from the mitochondrial genes
      coding for 16S rRNA and Cytochrome Oxidase subunit I demonstrated significant
      relationships between S. scabiei MtDNA haplotypes, host species and geographical
      location. Multi-locus genotyping using 15 microsatellite markers substantiated
      previous data that gene flow between scabies mite populations on human and dog
      hosts is extremely rare in northern Australia. These data clearly support our
      previous contention that control programs for human scabies in endemic areas with
      sympatric S. scabiei var. hominis and var. canis populations must focus on human
      to-human transmission. The genetic division of dog and human derived scabies
      mites also has important implications in vaccine and diagnostic test development
      as well as the emergence and monitoring of drug resistance in S. scabiei in
      northern Australia.

PMID- 15157768
TI  - Molecular basis of non-virulence of Trypanosoma cruzi clone CL-14.
AB  - We investigated the properties of metacyclic trypomastigotes of non-virulent
      Trypanosoma cruzi clone CL-14, as compared to the parental isolate CL. In
      contrast to the CL isolate, which produces high parasitemias in mice, metacyclic
      forms of clone CL-14 failed to produce patent infection. In vitro, the number of
      clone CL-14 parasites that entered epithelial HeLa cells, after 1 h incubation,
      was approximately four-fold lower than that of the CL isolate and at 72 h post
      infection intracellular replication was not apparent whereas cells infected with
      the CL isolate contained large number of parasites replicating as amastigotes. CL
      isolate metacyclic forms were long and slender, with the kinetoplast localised
      closer to the nucleus than to the posterior end, whereas clone CL-14 parasites
      were shorter, with the kinetoplast very close to the posterior end. Cysteine
      proteinase cruzipain and trans-sialidase activities were lower in CL isolate than
      in clone CL-14. The surface profile was similar, except that the expression of
      gp82, the stage-specific glycoprotein that promotes CL isolate mucosal infection
      in vivo and host cell invasion in vitro, was greatly reduced on the surface of
      clone CL-14 metacyclic forms. Genistein, a specific inhibitor of protein tyrosine
      kinase, which is activated in CL isolate by binding of gp82 to its host cell
      receptor, did not affect host cell entry of clone CL-14. In contrast with CL
      isolate, the infectivity of clone CL-14 was not affected by phospholipase C
      inhibitor U73122 but was diminished by a combination of ionomycin plus NH(4)Cl,
      which releases Ca(2+) from acidic vacuoles. Internalisation of clone CL-14, but
      not of CL isolate, was significantly increased by treating parasites with
      neuraminidase, which removes sialic acid from the mucin-like surface molecule
      gp35/50. Taken together, our data suggest an association between the non
      virulence of clone CL-14 metacyclic forms and the reduced expression of gp82,
      which precludes the activation of signal transduction pathways leading to
      effective host cell invasion.

PMID- 15157769
TI  - Eimeria maxima TRAP family protein EmTFP250: subcellular localisation and
      induction of immune responses by immunisation with a recombinant C-terminal
      derivative.
AB  - EmTFP250 is a high molecular mass, asexual stage antigen from Eimeria maxima
      strongly associated with maternally derived immunity to this protozoan parasite
      in hatchling chickens. Cloning and sequence analysis has predicted the antigen to
      be a novel member of the thrombospondin-related anonymous protein (TRAP) family
      of apicomplexan parasites. Members of the TRAP family are microneme proteins and
      are associated with host cell invasion and apicomplexan gliding motility. In
      order to assess the immunogenicity of EmTFP250, a C-terminal derivative encoding
      a low complex, hydrophilic region and putative transmembrane domain/cytosolic
      tail was expressed in a bacterial host system. The recombinant protein was used
      to immunise mice and chickens and found to induce strong IgG responses in both
      animal models as determined by specific ELISAs. Using Western blotting,
      protective maternal IgG antibodies previously shown to recognise native EmTFP250
      recognised the recombinant protein and, in addition, antibodies raised against
      the recombinant protein were shown to recognise native EmTFP250. Localisation
      studies employing immuno-light microscopy and immuno-electron microscopy showed
      that antibodies to the recombinant protein specifically labeled micronemes within
      merozoites of E. maxima. Furthermore, antibodies to the recombinant EmTFP250
      derivative showed similar labeling of micronemes within merozoites of Eimeria
      tenella. This study is further suggestive of a functional importance for EmTFP250
      and underscores its potential as a candidate for a recombinant vaccine targeting
      coccidiosis in chickens.

PMID- 15157770
TI  - Comparative analysis of two 14-3-3 homologues and their expression pattern in the
      root-knot nematode Meloidogyne incognita.
AB  - 14-3-3 proteins are highly conserved ubiquitous proteins found in all eukaryotic
      organisms. They are involved in various cellular processes including signal
      transduction, cell-cycle control, apoptosis, stress response and cytoskeleton
      organisation. We report here the cloning of two genes encoding 14-3-3 isoforms
      from the plant parasitic root-knot nematode Meloidogyne incognita, together with
      an analysis of their expression. Both genes were shown to be transcribed in
      unhatched second stage larvae, infective second stage larvae, adult males and
      females. The Mi-14-3-3-a gene was shown to be specifically transcribed in the
      germinal primordium of infective larvae, whereas Mi-14-3-3-b was transcribed in
      the dorsal oesophageal gland in larvae of this stage. The MI-14-3-3-B protein was
      identified by mass spectrometry in in vitro-induced stylet secretions from
      infective larvae. The stability and distribution of MI-14-3-3 proteins in host
      plant cells was assessed after stable expression of the corresponding genes in
      tobacco BY2 cells.

PMID- 15157771
TI  - Glass formation in plant anhydrobiotes: survival in the dry state.
AB  - Anhydrobiotes can resist complete dehydration and survive the dry state for
      extended periods of time. During drying, cytoplasmic viscosity increases
      dramatically and in the dry state, the cytoplasm transforms into a glassy state.
      Plant anhydrobiotes possess large amounts of soluble non-reducing sugars and
      their state diagrams resemble those of simple sugar mixtures. However, more
      detailed in vivo measurements using techniques such as Fourier transform infrared
      spectroscopy and electron paramagnetic resonance spectroscopy reveal that these
      intracellular glasses are complex systems with properties quite different from
      those of simple sugar glasses. Intracellular glasses exhibit a high molecular
      packing and slow molecular mobility, resembling glasses made of mixtures of
      proteins and sugars, which potentially interact with additional cytoplasmic
      components such as salts, organic acids, and amino acids. Above the glass
      transition temperature, the cytoplasm of biological systems still exhibits a high
      stability and low molecular mobility, which could serve as an ecological
      advantage. All desiccation-tolerant organisms form glasses upon drying, but
      desiccation-sensitive organisms generally lose their viability during drying at
      water contents at which the glassy state has not yet been formed, suggesting that
      other factors are necessary for desiccation tolerance. Nevertheless, the
      formation of intracellular glasses is indispensable to survive the dry state.
      Storage stability of seeds and pollens is related to the molecular mobility and
      packing density of the intracellular glass, suggesting that the characteristic
      properties of intracellular glasses provide stability for long-term survival.

PMID- 15157772
TI  - Longevity of cryogenically stored seeds.
AB  - Though cryogenic storage is presumed to provide nearly infinite longevity to
      cells, the actual shelf life achieved under ultra-cold temperatures has not been
      addressed theoretically or empirically. Here, we report measurable changes in
      germination of dried seeds stored under liquid nitrogen conditions for >10 years.
      There was considerable variability in the extent of deterioration among species
      and accessions within a species. Aging time courses for lettuce seeds stored at
      temperatures between 50 and -196 degrees C were fit to a form of the Avrami
      equation to determine rate coefficients and predict half-life of accessions. A
      reduction in the temperature dependency on aging rate, determined as a break in
      the Arrhenius plot, occurred at about -15 degrees C, and this resulted in faster
      deterioration than anticipated from extrapolation of kinetics measured at higher
      temperatures. The break in Arrhenius behavior occurred at temperatures in between
      the glass transition temperature (28 degrees C) and the Kauzmann temperature (-42
      degrees C) and also coincided with a major triacylglycerol phase change (-40 to 
      7 degrees C). In spite of the faster than anticipated deterioration, cryogenic
      storage clearly prolonged shelf life of lettuce seeds with half-lives projected
      as approximately 500 and approximately 3400 years for fresh lettuce seeds stored
      in the vapor and liquid phases of liquid nitrogen, respectively. The benefit of
      low temperature storage (-18 or -135 degrees C) on seed longevity was
      progressively lost if seeds were first stored at 5 degrees C. Collectively, these
      results demonstrate that lowering storage temperature progressively increases
      longevity of seeds. However, cryogenic temperatures were not sufficient to stop
      deterioration, especially if initial stages of aging were allowed to progress at
      higher storage temperatures. This work contributes to reliable assessments of the
      potential benefit and cost of different genebanking strategies.

PMID- 15157773
TI  - Beneficial effects of supplemental buffer and substrate on energy metabolism
      during small bowel storage.
AB  - Successful preservation of small bowel (SB) is closely correlated with the
      maintenance of cellular energetics. This study was designed to assess the ability
      of a modified UW solution supplemented with buffer and glucose to facilitate ATP
      production during cold storage. In part A, rats SB (n = 4) were flushed
      vascularly as follows: Group 1, UW solution (control); Group 2, HUW solution
      (UW+90 mM histidine). Inclusion of histidine resulted in a >3-fold increase in
      buffering capacity over the pH range 7.4-6.8. Positive effects of histidine on
      ATP and energy charge were apparent after 4-10h storage. Examination of the key
      regulatory enzyme, Phosphofructokinase (PFK), reflected a sustained activation
      was over 1-4h in the HUW group only. In part B, groups were vascularly flushed as
      follows: Group 1, HUW solution (control); Group 2, Group 1+20mM glucose; and
      Group 3, Group 2+luminal flush. Elevated ATP and total adenylates over 2-10h in
      Group 3 compared to control were a direct consequence of improved glycolytic
      activity. This data supports the hypothesis that tissue energetics can be
      significantly improved during cold storage using a histidine-buffered UW solution
      supplemented with carbohydrate substrate.

PMID- 15157774
TI  - Effects of dimethyl sulfoxide and glycine on cryopreservation induced damage of
      plasma membranes and mitochondria to striped bass (Morone saxatilis) sperm.
AB  - Intact plasma membrane and functional mitochondria are important attributes for
      the fertilization capacity of fish sperm. In the present study, dimethyl
      sulfoxide (Me(2)SO) and glycine were investigated in an effort to improve plasma
      membrane integrity and mitochondrial function in cryopreserved striped bass
      (Morone saxatilis) sperm. Prior to freezing, no concentration of Me(2)SO (2.5, 5
      or 10%) was found to affect (P>0.05) the integrity of plasma membranes after
      sperm were exposed for 10 min. However, mitochondrial function decreased (P>0.05)
      with increasing Me(2)SO concentration. Both fluorescent staining and microscopic
      examination of the ultrastructure of post-thaw plasma membranes indicated that
      with increasing Me(2)SO concentration, plasma membranes were better protected,
      and 10% Me(2)SO had the highest percentage of sperm with plasma membranes intact.
      However, sperm mitochondrial function decreased (P>0.05) with increasing Me(2)SO
      concentration. The inverse relationship between plasma membrane integrity and
      mitochondrial function, given the Me(2)SO concentration, suggests that care must
      be taken to select Me(2)SO concentration that will maximize the protection of
      both plasma membranes and mitochondrial function. The addition of glycine to the
      cryomedia increased (P<0.05) the percentage of sperm with post-thaw functional
      mitochondria and ATP content. However glycine did not provide (P<0.05) protection
      to post-thaw plasma membrane integrity. The highest percentage of sperm with both
      intact plasma membranes and functional mitochondria was obtained with 7.5%
      Me(2)SO and 75 mM glycine.

PMID- 15157775
TI  - Advanced hepatic tissue destruction in ablative cryosurgery: potentials of
      intermittent freezing and selective vascular inflow occlusion.
AB  - Recent studies indicate that cryosurgery represents a promising approach to treat
      non-resectable liver tumors. To improve parenchymal tissue destruction, a variety
      of modifications of the freeze-thaw procedure have been suggested, including
      repetitive freezing and portal-triad cross-clamping. The aim of the present study
      was to analyze whether intermittent freezing by application of a double freeze
      thaw procedure or selective vascular inflow occlusion are more effective than a
      single freeze-thaw cycle to achieve complete hepatic tissue destruction. Using a
      porcine model, intrahepatic cryolesions were induced by freezing the hepatic
      tissue for a total of 15 min (n=6, SF). Additional animals (n=6) underwent a
      double freeze-thaw cycle of 7.5 min each (DF). A third group of animals (n=6) was
      treated by a single 15-min freeze-thaw cycle during selective vascular inflow
      occlusion (VO-SF). Seven days after freezing, DF did not change the volume of the
      cryolesion (25.4+/-1.7 cm(3)) compared to SF (29.9+/-3.7 cm(3)), however,
      resulted in enhanced destruction of hepatocyte nuclear morphology (DF-score:
      2.4+/-0.2 versus SF-score: 1.1+/-0.3; p<0.05) and attenuated leukocyte
      infiltration within the margin of the cryolesion (DF-score: 1.5+/-0.2 versus SF
      score: 2.8+/-0.1; p<0.05). VO-SF was also effective to significantly enhance
      destruction of hepatocyte nuclear morphology (2.8+/-0.1; p<0.05 versus SF), but,
      additionally, markedly increased the volume of the cryolesions (43.3+/-5.3 cm(3);
      p<0.05 versus SF and DF). Interestingly, VO-SF further increased the number of
      apoptotic cells, while leukocyte infiltration (2.3+/-0.3) was not affected
      compared to that after SF-treatment. Thus, our data indicate that both DF and VO
      SF are effective to enhance parenchymal cell destruction within the margin of the
      cryolesion. VO-SF additionally increases the volume of the lesion and may
      therefore be most attractive for successful clinical application.

PMID- 15157776
TI  - Subzero nonfreezing cryopresevation of rat hearts using antifreeze protein I and
      antifreeze protein III.
AB  - The purpose of the present study was to evaluate whether AFPs protect the heart
      from freezing and improve survival and viability in subzero cryopreservation.
      Hearts were subject to 5 preservation protocols; University of Wisconsin solution
      (UW) at 4 degrees C, UW at -1.3 degrees C without nucleation, UW at -1.3 degrees
      C with nucleation, UW AFP I (15 mg/cm(3)) at -1.3 degrees C with nucleation, and
      in UW AFP III (15 mg/cm(3)) at -1.3 degrees C with nucleation. Hearts were
      preserved for 24, 28, and 32 h, rewarmed and connected to the working isolated
      perfusion system. Data [heart rate (HR), coronary flow (CF), and developed
      pressure (dP)] was collected 30 and 60 min after reperfusion. Hearts preserved at
      -1.3 degrees C without AFPs froze, while hearts preserved with AFP did not freeze
      when nucleation was initiated and survived. Survival and dP of hearts preserved
      for 24h at -1.3 degrees C using AFP III was better than those preserved at 4
      degrees C, (dP; 1.4 vs. 0.8, p<0.05). Four of six hearts and six of six hearts
      died when preserved at 4 degrees C for 28 and 32 h, respectively, all of the
      hearts that were preserved at -1.3 degrees C with or without AFPs survived after
      28 h (n=18) and 32 h (n=18). CF was higher in UW -1.3 degrees C group without
      attempted nucleation than in AFP I and AFP III groups after 28 and 32 h (3.4 vs.
      1.7, p<0.05, and 3.4 vs. 1.7, p<0.05, respectively). In conclusion, AFPs were
      found to protect the heart from freezing and improve survival and dP (AFP III) in
      prolonged subzero preservation.

PMID- 15157777
TI  - Thermal properties of ethylene glycol aqueous solutions.
AB  - Preventing ice crystallization by transforming liquids into an amorphous state,
      vitrification can be considered as the most suitable technique allowing complex
      tissues, and organs cryopreservation. This process requires the use of rapid
      cooling rates in the presence of cryoprotective solutions highly concentrated in
      antifreeze compounds, such as polyalcohols. Many of them have already been
      intensively studied. Their glass forming tendency and the stability of their
      amorphous state would make vitrification a reality if their biological toxicity
      did not reduce their usable concentrations often below the concentrations
      necessary to vitrify organs under achievable thermal conditions. Fortunately, it
      has been shown that mixtures of cryoprotectants tend to reduce the global
      toxicity of cryoprotective solutions and various efficient combinations have been
      proposed containing ethanediol. This work reports on the thermal properties of
      aqueous solutions with 40, 43, 45, 48, and 50% (w/w) of this compound measured by
      differential scanning calorimetry. The glass forming tendency and the stability
      of the amorphous state are evaluated as a function of concentration. They are
      given by the critical cooling rates v(ccr)above which ice crystallization is
      avoided, and the critical warming rates v(cwr) necessary to prevent ice
      crystallization in the supercooled liquid state during rewarming. Those critical
      rates are calculated using the same semi-empirical model as previously. This work
      shows a strong decrease of averaged critical cooling and warming rates when
      ethanediol concentration increases, V(ccr) and V(cwr) = 1.08 x 10 (10) K/min for
      40% (w/w) whereas V(ccr) = 11 and V(cwr) = 853 K/min for 50% (w/w). Those results
      are compared with the corresponding properties of other dialcohols obtained by
      the same method. Ethylene glycol efficiency is between those of 1,2-propanediol
      and 1,3-propanediol.

PMID- 15157779
TI  - Ice nucleation in solutions and freeze-avoiding insects-homogeneous or
      heterogeneous?
AB  - This article challenges the common view that solutions and cold-hardy freeze
      avoiding insects always freeze by heterogeneous nucleation. Data are presented to
      show that the nucleation temperatures of a variety of solutions and freeze
      avoiding insects are a function of the water volume as described by the data
      previously published by Bigg in 1953. The article also points out that the
      relationships between melting point depression and depression of nucleation
      temperature are different for samples undergoing homogeneous nucleation and those
      undergoing heterogeneous nucleation. Aqueous solutions and freeze-avoiding
      insects display a relationship like that of homogeneously nucleated samples. It
      is also argued that the identity of the "impurities" assumed to cause
      heterogeneous nucleation in aqueous solutions and insects is obscure and that the
      "impurities" have features which make their existence rather unlikely.

PMID- 15157778
TI  - Sperm cryopreservation of green swordtail Xiphophorus helleri, a fish with
      internal fertilization.
AB  - Sperm cryopreservation for fishes with internal fertilization is essentially
      unexplored although many species of these fishes are valuable biomedical research
      models. To explore methods for sperm cryopreservation within the live-bearing
      genus Xiphophorus, this study used X. helleri to evaluate the effects of
      cryoprotectant, osmotic pressure, cooling rate, equilibration time, and sperm-to
      extender ratio. Sperm motility and survival duration after thawing showed
      significant differences among different cryoprotectants with the highest motility
      at 10 min after thawing obtained with 14% glycerol. With subsequent use of 14%
      glycerol as the cryoprotectant, the highest motility after thawing was observed
      with Hanks' balanced salt solution (HBSS) at 300 mOsmol/kg. Samples cooled from 5
      to -80 degrees C at 20 degrees C/min yielded the highest post-thaw motility
      although no significant difference was found in the first 4h after thawing for
      cooling rates across the range of 20-35 degrees C/min. Evaluation of
      equilibration time revealed no significant difference between 20 min and 2h, but
      the highest motility at 10 min after thawing was found with a 20-min
      equilibration. Dilution ratios of sperm-to-extender at 1:20, 1:60, and 1:120
      showed no significant differences in motility and survival duration after
      thawing, but the dilution of sperm solutions with HBSS (320 mOsmol/kg)
      immediately after thawing reduced the decline of sperm motility, and
      significantly prolonged the survival duration. Based on these findings, the
      highest average sperm motility (77%) at 10 min after thawing was obtained when
      sperm were suspended in HBSS at 300 mOsmol/kg with 14% glycerol as
      cryoprotectant, diluted at a ratio of sperm to HBSS-glycerol of 1:20,
      equilibrated for 10 min, cooled at 20 degrees C/min from 5 to -80 degrees C
      before being plunged in liquid nitrogen, and thawed in a 40 degrees C water bath
      for 7s. If diluted immediately after thawing, sperm frozen by the protocol above
      retained continuous motility after thawing for more than 8 days when stored at 4
      degrees C.

PMID- 15157780
TI  - Ex-vivo study of flow dynamics and endothelial cell structure during extended
      hypothermic machine perfusion preservation of livers.
AB  - Liver transplantation is often the only effective treatment for end stage liver
      diseases resulting from cirrhosis, hepatitis, progressive jaundice, and biliary
      atresia. Hypothermic machine perfusion (HMP) preservation may enhance donor pool
      by extending preservation time and reclaiming marginal donor livers including
      those from non-heart beating donors (NHBD), as demonstrated in the kidney.
      However, current HMP protocols have not been successful in improving extended
      preservation of livers and the major cause of preservation injury remains
      unknown. An intravital microscopy study was conducted to understand the flow
      dynamics of sinusoidal perfusion during 24h HMP with cold modified University of
      Wisconsin (UW) solution. Fluorescein isothiocynate (FITC) labeled albumin was
      utilized to visualize microvascular space and FITC labeled red blood cells (RBCs)
      were used to visualize flow dynamics during HMP. A heterogeneous flow pattern
      with regions of red cell stasis was observed after 24-h HMP. To examine the cause
      of red cell stasis, intravital and confocal microscopy studies of endothelial
      cells (ECs) structure labeled with DiI acetylated low-density lipoprotein (DiI
      acLDL) were conducted. These studies suggest that morphological changes in EC
      structures occurred during 24h HMP, which may cause obstruction to the sinusoidal
      flow. Histological findings confirm these results. As a result, heterogeneous
      flow pattern, red cell stasis, and edema occur, which may lead to the failure of
      these tissues following extended HMP.

PMID- 15157781
TI  - The osmotic characteristics of human fetal liver-derived hematopoietic stem cell
      candidates.
AB  - Hematopoietic stem cells derived from fetal liver have promising therapeutic
      potential for allotransplantation but require a specific protocol to minimize the
      damage produced by cryopreservation procedures. In this study, a fundamental
      approach was applied for designing a cell preservation protocol. To this end, the
      biophysical characteristics that describe the osmotic reaction of CD34(+)CD38(-)
      human fetal liver stem cell candidates were studied using fluorescent microscopy.
      The osmotically inactive volume of the stem cell candidates was determined as 48%
      of the isotonic volume. The permeability coefficients for water and Me(2)SO were
      determined at T = +22 degree C: L(p) = 0.27 +/- 0.03 microm x min(-1)atm(-1),
      P(Me(2)SO)) = 2.09 +/- 0.85 x 10 (-4) cm x min(-1), sigma (Me(2)SO)) = 0.63 +/-
      0.03 and at T = +12 degree C: L(p) = 0.15 +/-0.02 microm x min(-1)atm(-1),
      P(Me(2)SO)) = 6.44 +/-1.42 x 10 (-5) cm x min(-1), sigma (Me(2)SO)) = 0.46 +/-
      0.05. The results obtained suggest that post-hypertonic and hypotonic stress are
      the possible reasons for damage to a CD34(+)CD38(-) cell during the
      cryopreservation procedure.

PMID- 15157782
TI  - Blastocysts derived from in vitro-fertilized cat oocytes after vitrification and
      dilution with sucrose.
AB  - Experiments were conducted to find an optimal incubation period in a sucrose
      solution during dilution of cryoprotectants for obtaining a higher level of
      survival and development of cat oocytes cryopreserved by vitrification method. In
      the first experiment, in vitro-matured fresh oocytes were exposed to 0.5M sucrose
      solution for 1 or 5 min before in vitro fertilization (IVF). The percentage of
      development to the blastocyst stage significantly decreased in oocytes exposed
      for 5 min, compared with oocytes exposed for 1 min and control oocytes without
      exposure to sucrose (P<0.05). In the second experiment, oocytes that had been
      vitrified in 40% ethylene glycol and 0.3M sucrose were liquefied and then
      incubated in 0.5M sucrose for 0.5, 1 or 5 min to dilute the cryoprotectant. The
      percentage of cleavage (>or=2-cell stage) of vitrified-liquefied oocytes
      incubated for 0.5 min was significantly higher (P<0.05) than that of other
      groups. Development of vitrified-liquefied oocytes to the morula and blastocyst
      stages after IVF was observed only in oocytes incubated in sucrose for 0.5 min.
      The present study indicates that the oocytes have sensitivity to the toxic effect
      of sucrose and that the incubation period during dilution of the cryoprotectant
      is of critical importance for developmental competence of vitrified-liquefied cat
      oocytes.

PMID- 15157783
TI  - The use of flow cytometry in the evaluation of cell viability of cryopreserved
      sperm of the marine shrimp (Litopenaeus vannamei).
AB  - Although the cryopreservation of penaeid prawn sperm or embryos has definite
      applications in the aquaculture industry, there is no protocol routinely used for
      this procedure. One of the main problems relies on the limitations for the
      determination of sperm cell viability. In this study, we evaluated the toxicity
      and cryoprotectant effect of four agents, at three different concentrations, in
      sperm suspension, spermatic mass, and complete spermatophore of the marine shrimp
      Litopenaeus vannamei. Cells were frozen by fast and slow cooling rates. After
      thawing, they were analyzed by optical microscopy and flow cytometry, which was
      also utilized to determine spermatic viability by DNA staining with propidium
      iodine. Considering viability by morphotype analysis, the best result was
      obtained when the spermatic mass was frozen by slow cooling rate in the presence
      of methanol (61.6%). There was a positive correlation between morphotype analysis
      and flow cytometry, although the percentage of viable cells was always lower when
      determined by the later. These results show that flow cytometry is a valuable
      tool to evaluate sperm cell viability in decapod species and it is more sensitive
      technique than optical microscopy.

PMID- 15157784
TI  - Theoretical analysis of unidirectional intercellular ice propagation in
      stratified cell clusters.
AB  - A recently published theoretical analysis of intercellular ice propagation in
      stratified cell clusters comprising concentric spherical layers, by Zhang, Xu,
      Sandison, and Zhang [Cryobiology 47 (2003) 143], has been examined and is shown
      to be flawed. New equations are derived subject to simplifying assumptions
      implicit in the theoretical model presented by Zhang and co-workers. The
      conclusion by Zhang and colleagues that intercellular ice propagation can be
      assumed to be instantaneous is demonstrated to be invalid.

PMID- 15157785
TI  - Extensive freezing necessary to ensure liver tumor ablation.

PMID- 15157788
TI  - Intrauterine devices and reproductive health: American women in feast and famine.
AB  - Intrauterine contraception has been available in the United States since the
      early 1960s. During the past 4 decades, American women have mainly used nine
      different devices and accumulated approximately 47 million person-years of use.
      Interest in IUDs, as expressed by both use patterns and market forces that
      created and retired products, varied tremendously over this period. In the peak
      years, women had unfettered access to, and choice of, IUDs, over time
      availability has declined. The American experience with IUDs involved a unique
      combination of factors: invention, expansion of publicly funded services, mass
      media, medical missteps, conflicting research, medical opinion and tort law. The
      IUD generated a controversial balance sheet of risks, benefits and reputation
      that still impacts reproductive health today.

PMID- 15157787
TI  - The federal abortion ban: a clinical and moral dilemma, and international policy
      setback.

PMID- 15157789
TI  - Costs and net health effects of contraceptive methods.
AB  - BACKGROUND: Pregnancy and contraceptive methods both have important health
      effects that include risks and benefits. The net impact of contraception on
      women's health has not been reported previously. STUDY DESIGN: This is a cost
      utility analysis using a Markov model evaluated by Monte Carlo simulation using
      the societal perspective for costs. The analysis compared 13 methods of
      contraception to nonuse of contraception with respect to healthcare costs and
      quality-adjusted life years (QALYs). Discounting was applied for future costs and
      health effects. The base-case analysis applies to women of average health and
      fertility, ranging from 15 to 50 years of age, who are sexually active in a
      mutually monogamous relationship; smoking rates observed in women of reproductive
      age were used. Sensitivity analysis extended the analysis to nonmonogamous status
      and smoking status. RESULTS: Compared with use of no contraception, contraceptive
      methods of all types result in substantial cost savings over 2 years, ranging
      from US$5907 per woman for tubal sterilization to US$9936 for vasectomy and
      health gains ranging from 0.088 QALYs for diaphragm to 0.147 QALYs for depot
      medroxyprogesterone acetate. Compared with nonuse, even with a time horizon as
      short as 1 year, use of any method other than sterilization results in financial
      savings and health gains. Most of the financial savings and health gains were due
      to contraceptive effects. In a population of patients, even modest increases in
      the use of the most effective methods result in financial savings and health
      gains. CONCLUSIONS: Every method of contraception dominates nonuse in most
      clinical settings. Increasing the use of more effective methods even modestly at
      the expense of less effective methods will improve health and reduce costs.
      Methods that require action by the user less frequently than daily are both less
      costly and more effective than methods requiring action on a daily basis.

PMID- 15157790
TI  - The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study.
AB  - This open-label, nonrandomized study compared changes in hemostatic variables
      during NuvaRing and oral levonorgestrel 150 microg/ethinylestradiol 30 microg
      (LNG/EE) use for six cycles. Eighty-seven women started the study, 44 with
      NuvaRing and 43 with the LNG/EE oral contraceptive. For most procoagulation
      variables, there was no difference between NuvaRing and oral LNG/EE; only Factor
      VII levels increased in the NuvaRing group and decreased in the LNG/EE group. The
      majority of assessed variables show that anticoagulation and fibrinolytic
      activity was comparable between the NuvaRing and oral LNG/EE groups. Antithrombin
      activity and protein C activity both tended to be higher with NuvaRing. Levels of
      tissue plasminogen activator decreased in both groups but the reduction was
      smaller with NuvaRing. There were no significant differences in fibrin turnover
      between the treatment groups. The data show that both NuvaRing and oral LNG/EE
      are associated with a minimal effect on hemostatic variables.

PMID- 15157792
TI  - Serum resistin levels in women taking combined oral contraceptives containing
      desogestrel or gestodene.
AB  - Resistin is a hormone secreted by adipose tissue that could be involved in the
      development of insulin resistance. Previous studies confirmed that endogenous sex
      steroids may influence serum resistin concentration in women. The aim of our
      study was to investigate the influence of combined oral contraceptives containing
      desogestrel or gestodene on circulating levels of resistin. Fifty-three women
      were enrolled in the study. Thirteen patients received 20 microg
      ethinylestradiol/150 microg desogestrel, 15 women were treated with 20 microg
      ethinylestradiol/75 microg gestodene, 11 with 30 microg ethinylestradiol/150
      microg desogestrel and 14 with 30 microg ethinylestradiol/75 microg gestodene.
      Blood samples for estimation of serum resistin and insulin levels were drawn
      before administration of oral contraceptive and after 6 cycles of therapy. We
      found that serum resistin level remained unchanged in women receiving
      ethinylestradiol/desogestrel and was reduced in women treated with formulations
      containing gestodene. We conclude that ethinylestradiol combined with desogestrel
      or gestodene is unlikely to induce insulin resistance through resistin pathway.

PMID- 15157791
TI  - Cycle control, quality of life and acne with two low-dose oral contraceptives
      containing 20 microg ethinylestradiol.
AB  - OBJECTIVES: Poor cycle control and tolerability can be reasons for irregular pill
      intake. This study compared the tolerability of two low-dose oral contraceptives
      and their effect on cycle control. METHODS: In this open, group-comparative,
      randomized multicenter trial in Germany and the Netherlands, women received
      either 20 microg ethinylestradiol plus 150 microg desogestrel (20EE/DSG; n = 500)
      or 20 microg ethinylestradiol plus 100 microg levonorgestrel (20EE/LNG; n = 498)
      for six treatment cycles. Cycle control, dysmenorrhea and premenstrual syndrome
      (PMS) were assessed using diary cards. Tolerability was assessed using the self
      administered questionnaires Psychological General Well-Being Index (PGWBI) and
      the Profile of Mood States (POMS). Acne was assessed by objective (acne counts)
      and subjective (no, moderate, mild, severe) acne scoring of the facial area at
      baseline and treatment cycles 1, 3 and 6. RESULTS: A total of 404 (78.1%) and 384
      (75.3%) women in the 20EE/DSG and 20EE/LNG groups, respectively, completed the
      trial. The occurrence rate of irregular bleeding and spotting was statistically
      significantly higher with 20EE/LNG than with 20EE/DSG (0.18 vs. 0.13; p < 0.05).
      The mean number of bleeding-spotting days per cycle was statistically
      significantly higher with 20EE/LNG than with 20EE/DSG (0.63 vs. 0.48; p < 0.05).
      Early withdrawal bleeding was more frequent with 20EE/LNG (0.15 vs. 0.08; p <
      0.005), whereas continued withdrawal bleeding was more frequent with 20EE/DSG
      (0.32 vs. 0.45; p < 0.001); absence of withdrawal bleeding was comparable (0.06
      vs. 0.04, respectively). Thirteen subjects in the 20EE/LNG group and three in the
      20EE/DSG group discontinued due to unacceptable bleeding (p < 0.05). Dysmenorrhea
      and PMS decreased comparably in both groups. There were no differences between
      groups for the mean total scores of PGWBI or POMS at all time-points. Fewer acne
      lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles (p < 0.05). The
      subjective acne scores supported this finding. CONCLUSIONS: 20EE/DSG provided
      better cycle control than 20EE/LNG with less treatment discontinuation due to
      unacceptable bleeding. There were no apparent differences between the two groups
      regarding tolerability and quality of life. There was less acne with 20EE/DSG.

PMID- 15157793
TI  - Effectiveness of preabortion counseling on postabortion contraceptive use.
AB  - In a randomized trial, the effect of preabortion counseling was evaluated and
      contraceptive use postabortion described. The 420 women, who were assigned into
      either an intervention group (n = 210) or a control group (n = 210), were
      followed-up 4-6 months later, a total of 148 and 128 women in each respective
      group. No significant difference was found between the two groups regarding
      contraceptive use after abortion (86%, 85%), which indicates no immediate
      intervention effect. The women, in both groups, who had previously undergone
      abortion were less likely to use contraception. The main contraceptive methods
      used by intervention and control groups were oral contraceptives (61% and 58%,
      respectively) and injectables (12% and 11%). Choice of method was mainly based on
      women's prior perception of effectiveness and convenience of use. A majority of
      the women in both groups could not specify their contraceptive plans. A
      postrandomization inequality regarding age, education and parity in the two
      groups had, however, to be taken into account. Intensive contraceptive counseling
      before abortion may not be effective, but those who are at higher risk of
      unplanned pregnancy need special attention.

PMID- 15157794
TI  - Implanon use in Thai women above the age of 35 years.
AB  - A prospective study of Implanon implant use in women older than 35 was conducted
      in Bangkok, Thailand. The purposes of this study were to evaluate the menstrual
      pattern and side effects of Implanon in 51 women followed for 6 months. Their
      mean age was 39.7 years. Most acceptors had completed primary school. No
      accidental pregnancies occurred in 6 months of use. The most common menstrual
      pattern in these acceptors was irregular bleeding followed by amenorrhea. The
      major side effect was irregular bleeding. There was no significant change in body
      weight, body mass index and diastolic blood pressure during the 6-month follow-up
      period, but systolic blood pressure declined. Implanon implant use is a safe and
      effective contraceptive method and should become another choice for contraception
      in women aged above 35 years who have contraindications for oral contraceptive
      use.

PMID- 15157795
TI  - Ethnic Chinese women's perceptions about condoms, withdrawal and rhythm methods
      of birth control.
AB  - OBJECTIVE: To gain a better understanding of ethnic Chinese women's perceptions
      and experiences of using barrier and rhythm methods of contraception in order to
      improve contraceptive counseling at abortion clinics. DESIGN: Qualitative
      descriptive study. SETTING: Urban abortion clinic. PARTICIPANTS: Forty ethnic
      Chinese women presenting for abortion. METHOD: Data were collected in semi
      structured interviews by one interviewer who is fluent in English, Mandarin and
      Cantonese. Transcribed interviews were systematically analyzed to identify
      salient themes. MAIN FINDINGS: All of the women interviewed had used condoms
      (none with spermicide), 20 had used rhythm and 17 withdrawal, usually a
      combination of two or three of these methods. Many women noted that these methods
      are under male control and talked about the difficulty negotiating their use with
      partners. The majority of women using rhythm were unable to correctly identify
      "safe periods."

PMID- 15157796
TI  - Restoration of fertility in vasectomized men using percutaneous vasal or
      epididymal sperm aspiration.
AB  - OBJECTIVE: To restore fertility of vasectomized men using percutaneous epididymal
      sperm aspiration (PESA) and percutaneous vasal sperm aspiration (PVSA) via
      intrauterine insemination (IUI). PATIENTS: Twenty-eight vasectomized men who
      required restoration of their fertility with PESA, PVSA and IUI. RESULTS: Of 28
      vasectomy reversal subjects, 16 cycles of IUI using vasal sperm by percutaneous
      aspiration were performed in 16 subjects and 6 pregnancies were achieved. IUIs
      with epididymal sperm by percutaneous aspiration were carried out in 12 subjects
      with epididymal obstruction due to vasovasostomy for vasectomy reversal, and 2
      pregnancies were achieved using caudal and epididymal sperm by percutaneous
      aspiration, respectively. CONCLUSION: The PESA-IUI and PVSA-IUI techniques are
      attractive, economical and effective for vasectomy reversal. The pregnancy by IUI
      using PESA and PVSA reveals that the caput epididymal sperm possess fertilization
      capacity in female reproductive tract and provides a new approach for the
      restorative fertility of vasectomized men.

PMID- 15157797
TI  - The reliability of the anchoring concept for suspension of bioactive substances
      in the human uterus evaluated by measuring the removal force: results after long
      term use.
AB  - OBJECTIVE: The objective of the present study is to report on the force needed to
      remove the implanted GyneFix intrauterine contraceptive device (IUD) from the
      uterine cavity. This study is the first long-term study on the retrieval of the
      anchored IUD. STUDY DESIGN: A two-center, noncomparative study to measure the
      force needed to remove the IUD in 251 women. A dynamometer (Pesola, Switzerland)
      was used to measure the removal force in newtons. RESULTS: The results of this
      study show a mean removal force of 6.2 and 6.1 newtons, respectively (range, 0
      10), in parous and nulligravid or nulliparous women (p = 0.62). There was no
      difference in removal force for those women with a duration of use either less
      than 60 months or longer than 60 months (median of 6 newtons in both groups; p =
      0.22). CONCLUSIONS: The force needed to remove the GyneFix IUD suggests that the
      implantation technology used in the insertion of the device is reliable, provided
      the anchoring knot is properly inserted in the fundal myometrium. The results of
      this study indicate that early expulsion of the device could be explained by
      failure to implant the knot adequately (no implantation or partial implantation),
      which requires a degree of skill. The present study does not provide an
      explanation for the occurrence of late expulsion, although some speculations can
      be made.

PMID- 15157798
TI  - The effect of Nestorone on gonadotropic cells in pituitary of rats.
AB  - The implant containing Nestorone is a promising long-acting contraceptive
      especially suitable for lactating women. In this study, two experiments were
      designed to observe the effect of Nestorone on the gonadotropic cells in
      pituitary of rats for analyzing its antiovulation mechanism. In the first
      experiment, the ED50 of Nestorone on inhibiting ovulation was found to be 1.32
      mg/kg. The serum luteinizing hormone (LH) levels were significantly lower 60 h
      after being treated with Nestorone at 8:30-9:00 a.m. on Day 2 (D2) of estrus.
      Image analysis showed that the average size of the LH cells in groups treated
      with Nestorone at 2 or 4 mg/kg was larger than that of the control. In the group
      treated with 4 mg/kg, most of gonadotropic cells were regular round in shape.
      And, abundant granules in cytoplasm were found in those cells, which indicated
      that the LH stored in cells was not released. In the second experiment, the rats
      were treated with Nestorone at 5 mg/kg at 11:30-12:00 a.m. on D2 of estrus. The
      normal or higher expression of LHbeta mRNA in pituitary suggested that the
      synthesis of LH was not inhibited by the treatment with Nestorone. The expression
      of PR mRNA in pituitary was significantly lower than that of the control at 33 h
      after treatment. This might be a direct effect of Nestorone, since there were no
      differences in the serum E2 and P4 levels between the treated and the control
      group. It is concluded that Nestorone prevents ovulation through inhibition of LH
      secretion and it has no effect on synthesis of LH. Progesterone receptors in
      pituitary might be involved in this process, but further study is needed to gain
      more evidence.

PMID- 15157799
TI  - The force required to remove the frameless 0-suture IUD anchoring system:
      comparison between pre- and postmenopausal women.
AB  - OBJECTIVE: The objective of this short communication is to measure and compare
      the force needed to remove the implanted "0-suture" GyneFix intrauterine
      contraceptive device (IUD) and the "0-suture" FibroPlant trade mark -LNG
      intrauterine system (IUS) from the uterus of pre- and postmenopausal women. STUDY
      DESIGN: A nonrandomized comparative study in 119 pre- and postmenopausal women. A
      dynamometer (Pesola) was used to measure the removal force in newtons. RESULTS:
      The results of this study show a mean removal force of 8.5 and 9.5 newtons,
      respectively (range, 3-11 and 4.5-11), in pre- and postmenopausal women, which is
      significantly different (p = 0.003). CONCLUSIONS: The force needed to remove the
      IUD/IUS anchored in the myometrium of the uterine fundus of pre- and
      postmenopausal women is higher than the removal force found in previous studies
      in which the IUD consisted of a slightly thinner anchoring thread (00 instead of
      0 suture). The statistically significantly different removal force between the
      two groups has no clinical implications. The difference may reflect the increased
      compactness of the uterine tissue in the postmenopausal uterus.

PMID- 15157800
TI  - Effect of anesthesia on CBF, MAP and fMRI-BOLD signal in response to apnea.
AB  - Systemic effects of anesthesia on the dynamics of the apnea-induced Blood Oxygen
      Level Dependent (BOLD) signal is still not clear. In the present study, the
      dynamics of the fMRI-BOLD signal and blood flow using laser Doppler flowmetry
      (LDF) was studied in rats in response to apnea. Two anesthetics namely
      pentobarbital and urethane, hypothesized to have distinct effects on the mean
      arterial blood pressure (MAP) were used. During normoxic baseline conditions, MAP
      decreased in response to apnea in rats anesthetized with pentobarbital but
      increased with urethane. However, MAP did not change significantly in response to
      apnea during hyperoxic or hypercapnic baseline conditions with both anesthetics.
      LDF increased in response to apnea during normoxia, hyperoxia or hypercapnia and
      was influenced by MAP during normoxia. Apnea-induced BOLD signal dynamics was
      similar with both anesthetics, dominated by an alteration in arterial blood
      oxygenation and independent of changes in MAP. Our results suggest that
      anesthesia-dependent MAP change modulates the apnea-induced cerebral blood flow
      (CBF) response but has a minimal effect on the fMRI-BOLD signal probably due to
      uncoupling of CBF and oxygen consumption.

PMID- 15157802
TI  - The adult central nervous cholinergic system of a neurogenetic model animal, the
      zebrafish Danio rerio.
AB  - The central nervous cholinergic system of the zebrafish (Danio rerio), a model
      animal for neurogenetics, is documented here using immunohistochemical methods
      for visualizing choline acetyltransferase (ChAT), the acetylcholine synthesizing
      enzyme. Neuronal cell bodies containing ChAT are present in the telencephalon
      (lateral nucleus of ventral telencephalic area), preoptic region
      (anterior/posterior parvocellular and magnocellular preoptic nuclei),
      diencephalon (habenula, dorsal thalamus, posterior tuberculum), mesencephalon
      (Edinger-Westphal (EW) nucleus, oculomotor nerve nucleus, rostral tegmental
      nucleus, tectal type XIV neurons), isthmic region (nucleus lateralis valvulae,
      secondary gustatory-viscerosensory nucleus, nucleus isthmi (NI), perilemniscal
      nucleus, superior reticular nucleus (SRN)) and rhombencephalon (trochlear,
      trigeminal, abducens, facial, glossopharyngeal-vagal motor nerve nuclei, rostral
      and caudal populations of octavolateralis efferent neurons). In addition, some
      ChAT positive neurons are present in the rhombencephalic reticular formation, the
      central gray, and in cells accompanying the descending trigeminal tract. Obvious
      ChAT positive terminal fields are present in the supracommissural nucleus of area
      ventralis telencephali and the medial zone of area dorsalis telencephali,
      parvocellular superficial pretectal nucleus, torus semicircularis, medial
      octavolateralis nucleus, facial, glossopharyngeal, and vagal lobes, and in the
      inferior lobe (around the periventricular nucleus of the lateral recess and in
      the diffuse nucleus). The identification of all central nervous cholinergic
      systems provided here in this model system is pivotal for future detailed studies
      of their development and maintenance, e.g., with regard to the zebrafish ventral
      telencephalic and isthmic superior reticular neuronal populations, likely
      representing the homologues of at least part of the cholinergic basal forebrain
      and pedunculopontine/laterodorsal tegmental ascending activating systems of
      mammals, respectively.

PMID- 15157801
TI  - Effects of triflusal on oxidative stress, prostaglandin production and nitric
      oxide pathway in a model of anoxia-reoxygenation in rat brain slices.
AB  - Acetylsalicylic acid (ASA) is the most widely used drug in the prevention of
      ischemic vascular accidents, mainly because of its antithrombotic effect.
      Recently, evidence of a neuroprotective effect has appeared. The aim of this
      study was to evaluate the neuroprotective effect of triflusal, a fluorinated
      derivative of ASA, in a model of anoxia-reoxygenation in rat brain slices. Rats
      (n=10 per group) were treated for 7 days with 1, 10 or 50 mg/kg/day p.o. of
      triflusal or ASA or solvent (control group), then brain slices were obtained and
      subjected to a period of anoxia followed by 180 min of reoxygenation. We measured
      oxidative stress parameters (lipid peroxidation, glutathione system),
      prostaglandins (PGE(2)), nitric oxide pathway activity (NO) (nitrites+nitrates,
      constitutive and inducible NO synthase activity) and cell death (lactate
      dehydrogenase (LDH) efflux). Triflusal decreased cell death in rat brain slices
      subjected to reoxygenation after anoxia by 21%, 42% and 47% with 1, 10 and 50
      mg/kg/day, respectively. This effect was proportionately greater than the effect
      of ASA (0%, 25% and 24%). The antioxidant effects of triflusal on the biochemical
      mechanisms of cell damage studied here were also greater than the effects of ASA:
      lipid peroxidation was reduced by 29%, 35% and 36% with triflusal, and 0%, 19%
      and 29% with ASA. Inducible NO synthase activity was reduced by 25%, 27% and 30%
      with triflusal, and 0%, 25% and 24% with ASA. Triflusal can be considered an
      alternative to ASA as a neuroprotective agent, at least in the experimental model
      of anoxia-reoxygenation used in the present study.

PMID- 15157803
TI  - Paraquat-induced apoptotic cell death in cerebellar granule cells.
AB  - We examined the toxicity of paraquat, a possible environmental risk factor for
      neurodegenerative disorders like Parkinson's disease (PD). Paraquat is
      structurally similar to the neurotoxin MPP+ that can induce Parkinsonian-like
      features in rodents, non-human primates and human. Exposure of cerebellar granule
      cells to relatively low concentrations of paraquat (5 microM) produces apoptotic
      cell death with a reduction in mitochondrial cytochrome c content, proteolytic
      activation and caspase-3 activity increase and DNA fragmentation. Paraquat
      induced apoptosis was significantly attenuated by co-treatment of cerebellar
      granule cells with the radical scavenger vitamin E, suggesting that paraquat
      induced free radicals serve as important signal in initiation of cell death. As a
      decrease in mitochondrial cytochrome c content is also prevented by allopurinol,
      we suggest that xanthine oxidase plays an important role in the free radical
      production that precedes the apoptotic cascade and cell death after paraquat
      exposition.

PMID- 15157804
TI  - Differential thapsigargin-sensitivities and interaction of Ca2+ stores in human
      SH-SY5Y neuroblastoma cells.
AB  - In human SH-SY5Y neuroblastoma cells, two distinct intracellular Ca2+ stores, a
      KCl-/caffeine-sensitive and a carbachol-/IP3-sensitive store, were demonstrated
      previously. In this study, responses of these two intracellular Ca2+ stores to
      thapsigargin were characterized. Ca2+-release from these stores was evoked either
      by high K+ (100 mM KCl) or by 1 mM carbachol, and changes in the intracellular
      Ca2+ level were monitored using Fura-2 fluorimetry. A sequential stimulation
      protocol (KCl-->carbachol or vice versa) allowed evaluation of the individual
      contribution of different Ca2+ stores to the evoked intracellular Ca2+ ([Ca2+]i)
      transients and the dynamic interaction between them. Thapsigargin (0.05 nM - 20
      microM) alone induced a [Ca2+]i-transient. Both the carbachol- and the KCl-evoked
      [Ca2+]i-transients were inhibited by thapsigargin, but with very different
      sensitivities. Thapsigargin inhibited the carbachol-evoked [Ca2+]i-transients
      with (IC50 = 0.353 nM) or without (IC50 = 0.448 nM) a KCl-prestimulation, but an
      additional small component, with a much lower sensitivity (IC50=4814 nM), was
      observed in the absence of a KCl-prestimulation. In contrast, the KCl-evoked
      [Ca2+]i-transients displayed only one component with a very low sensitivity to
      thapsigargin in both absence (IC50=3343 nM) and presence (IC50=6858 nM) of a
      carbachol-prestimulation. These findings suggest that the sarco-/endoplasmic
      reticular Ca2+ ATPases associated with the KCl-/caffeine- and carbachol-/IP3
      sensitive intracellular Ca2+ stores differ from each other, either in types or in
      their post-translational modification. Such difference might play important role
      in the regulation of neuronal Ca2+ homeostasis.

PMID- 15157805
TI  - Effects of gonadal steroids on the input-output relationship of the corticospinal
      pathway in humans.
AB  - Most of our knowledge about gonadal steroid effects on the nervous system come
      from studies of limbic structures, while virtually nothing is known about the
      action of these hormones on the motor system. We carried out experiments on six
      healthy volunteer males to determine the threshold and gain of the input-output
      relationship (i.e. stimulus intensity vs. response size) of the corticospinal
      motoneurones in relation to the transient increase of gonadal steroids induced by
      a single intramuscular injection of human chorionic gonadotropin (hCG). The motor
      cortex was excited by focal transcranial magnetic stimuli and the evoked
      responses from the first dorsal interosseous (FDI) were recorded with surface
      electromyographic electrodes. In some experiments, the threshold and recruitment
      curve of the soleus H reflex were determined to assess the gonadal steroid
      effects on spinal motoneurones. All the subjects showed a significant decrease of
      cortical motor threshold concomitant with a significant increase of testosterone
      and oestradiol plasma concentrations. By contrast, there was no significant
      change of the slope of the curve expressing the relationship between the
      intensity of magnetic stimulation and the size of the muscle response. Both the
      threshold and slope of the H reflex were unaffected by the gonadal steroid
      levels. Latencies of the maximal FDI response to cortical and cervical magnetic
      stimulation were also unmodified. We conclude that gonadal steroids are involved
      in regulating the threshold of corticospinal motoneurones in humans. Our
      observations confirm that the threshold and gain of corticospinal motoneurones
      are determined by different neural mechanisms.

PMID- 15157806
TI  - Protective cap over CA1 synapses: extrasynaptic glutamate does not reach the
      postsynaptic density.
AB  - Numerous data indicate that nonsynaptic release of glutamate occurs both in
      normal and pathophysiological conditions. When reaching receptors in the
      postsynaptic density (PSD), glutamate (Glu) could affect the synaptic
      transmission. We have tested this possibility in the hippocampal CA1 synapses of
      rats, either by applying exogenous Glu to the CA1 neurons or by disruption of Glu
      transporter activity. L-Glu (400 microM) was directly applied to the hippocampal
      slices acutely isolated from the rats. It produced a strong inhibition of both
      ortho- and antidromically elicited action potentials fired by CA1 neurons while
      the excitatory postsynaptic current (EPSC) measured in these neurons remained
      totally unaffected. The optical isomer D-Glu which is not transported by the
      systems of Glu uptake inhibited not only orthodromic and antidromic spikes, but
      also EPSC. Non-specific glutamate transporter inhibitor DL-threo-beta
      hydroxyaspartic acid (THA, 400 microM) mimicked the effects of exogenous Glu and
      produced strong inhibition of both orthodromic and antidromic spikes, without any
      influence on the amplitude of EPSCs. Dihydrokainate (DHK, 300 microM), selective
      inhibitor of GLT-1 subtype of glutamate transporter, exerted a significant
      inhibitory action on the orthodromically evoked spikes and also on the EPSC. Our
      results indicate that extrasynaptic and PSD membranes of CA1 neurons form
      separate compartments differing in the mechanisms and efficiency of external Glu
      processing: the protection of PSD markedly prevails.

PMID- 15157807
TI  - Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio
      rerio).
AB  - Connections of the medial precommissural subpallial ventral telencephalon, i.e.,
      dorsal (Vd, interpreted as part of striatum) and ventral (Vv, interpreted as part
      of septum) nuclei of area ventralis telencephali, were studied in the zebrafish
      (Danio rerio) using two tracer substances (DiI or biocytin). The following major
      afferent nuclei to Vd/Vv were identified: medial and posterior pallial zones of
      dorsal telencephalic area, and the subpallial supracommissural and
      postcommissural nuclei of the ventral telencephalic area, the olfactory bulb,
      dorsal entopeduncular, anterior and posterior parvocellular preoptic and
      suprachiasmatic nuclei, anterior, dorsal and central posterior dorsal thalamic,
      as well as rostrolateral nuclei, periventricular nucleus of the posterior
      tuberculum, posterior tuberal nucleus, various tuberal hypothalamic nuclei,
      dorsal tegmental nucleus, superior reticular nucleus, locus coeruleus, and
      superior raphe nucleus. Efferent projections of the ventral telencephalon
      terminate in the supracommissural nucleus of area ventralis telencephali, the
      posterior zone of area dorsalis telencephali, habenula, periventricular
      pretectum, paracommissural nucleus, posterior dorsal thalamus, preoptic region,
      midline posterior tuberculum (especially the area dorsal to the posterior tuberal
      nucleus), tuberal (midline) hypothalamus and interpeduncular nucleus. Strong
      reciprocal interconnections likely exist between septum and preoptic
      region/midline hypothalamus and between striatum and dorsal thalamus
      (dopaminergic) posterior tuberculum. Regarding ascending activating/modulatory
      systems, the pallium shares with the subpallium inputs from the (noradrenergic)
      locus coeruleus, and the (serotoninergic) superior raphe, while the subpallium
      additionally receives such inputs from the (dopaminergic) posterior tuberculum,
      the (putative cholinergic) superior reticular nucleus, and the (putative
      histaminergic) caudal hypothamalic zone.

PMID- 15157809
TI  - A C-fiber reflex inhibition induced by electroacupuncture with different
      intensities applied at homotopic and heterotopic acupoints in rats selectively
      destructive effects on myelinated and unmyelinated afferent fibers.
AB  - The aims of this study were to explore the C-fiber reflex inhibition induced by
      electroacupuncture with different intensities applied at homotopic or heterotopic
      acupoints, and to determine the influence selectively destroyed myelinated and
      unmyelinated afferent fibers on the C-fiber reflex inhibition. In the ipsilateral
      local acupoint, the general behavior of the C-fiber reflex can be depressed by
      electroacupuncture below the threshold of Adelta-fiber activation.
      Electroacupuncture stimulation within the intensity of Adelta-fiber activation
      applied to the ipsilateral limb pretreated with cobra venom did not elicit
      inhibition of C-fiber reflex in rats with demyelinated sciatic nerve. However,
      heterotopic electroacupuncture below the threshold of Adelta-fiber activation was
      totally ineffective. In contralateral heterotopic acupoints, the C-fiber reflex
      can be depressed only by electroacupuncture with stimulating intensities
      exceeding thresholds of Adelta and C-fiber activation. Electroacupuncture stimuli
      applied to capsaicin-pretreated limb in the intensities of threshold of Adelta
      fiber and treble thresholds of C-fiber activation produced only a little
      inhibition of C-fiber reflex. Inhibitory intensity was roughly similar to that
      induced by the stimulation with intensity for the activation of Adelta-fiber in
      normal animal. In the spinalized animals transections at T6-T7 segments,
      regardless of intensities, the homotopic electroacupuncture stimulation only
      induced moderate depression of C-fiber reflex similar to that of Adelta-fiber
      activation; whereas, no matter what intensities of application, the inhibitory
      effects of C-fiber reflex disappeared totally by using heterotopic noxious
      electroacupuncture in these animals.

PMID- 15157808
TI  - Antiobesity effect of YM348, a novel 5-HT2C receptor agonist, in Zucker rats.
AB  - The purpose of the present study was to investigate the potency of (S)-2-(7-ethyl
      1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), a 5-HT2C receptor
      agonist, as an antiobesity agent in Zucker rats. Single oral administration of
      YM348 at 0.1, 0.3, 1 and 3 mg/kg significantly reduced food intake in a dose
      dependent manner. This effect of YM348 on food intake was inhibited by SB242084,
      a selective 5-HT2C receptor antagonist. In addition, single administration of
      YM348 significantly increased body temperature and calorie expenditure at doses
      of 0.3, 1 and 3 mg/kg, and 1 and 3 mg/kg p.o., respectively. The increasing
      effect of YM348 on body temperature and calorie expenditure was inhibited by
      SB242084. Chronic subcutaneous infusion of YM348 (3 and 30 mg/kg/day) for 2 weeks
      also decreased food intake. However, this hypophagic effect of YM348 was marked
      during the initial week of infusion but only minor in the second. In contrast, no
      diminution of effect on body temperature and calorie expenditure was seen on
      repeated administration of YM348 (1 mg/kg p.o.). Two weeks' subcutaneous infusion
      of YM348 (3 and 30 mg/kg/day) resulted in a significant decrease in body weight
      gain throughout the experiment. These results suggest that the maintenance of
      thermogenesis contributed to the reduced body weight by YM348. The ability of
      YM348 to decrease body weight in Zucker rats suggests its strong potential for
      development as an antiobesity agent in humans.

PMID- 15157810
TI  - Asymmetric activation of extracellular signal-regulated kinase 1/2 in rat
      vestibular nuclei by unilateral labyrinthectomy.
AB  - The expression of phosphorylated extracellular signal-regulated kinase 1/2 (pERK
      1/2) was evaluated in the vestibular nuclei (VN) of rats following unilateral
      labyrinthectomy (UL). Immunohistochemistry revealed a significant asymmetrical
      increase in pERK 1/2 expression in the VN, 5 min after UL, after which pERK 1/2
      immunoreactivity decreased rapidly and was undetectable by 90 min after UL. These
      results suggest that unilateral deafferentation of the vestibular system triggers
      intracellular signal pathways that activate ERK 1/2 in the VN.

PMID- 15157811
TI  - Eugenol exhibits antidepressant-like activity in mice and induces expression of
      metallothionein-III in the hippocampus.
AB  - Here we show that eugenol has an antidepressant-like activity comparable to that
      of imipramine using a forced swim test and a tail suspension test in mice.
      Furthermore, we show that both eugenol and imipramine induce brain-derived
      neurotrophic factor (BDNF) in the hippocampus with and without induction of
      metallothionein-III (MT-III), respectively. It may be possible that MT-III
      expression is involved in the exhibition of antidepressant-like activity of
      eugenol, not of imipramine.

PMID- 15157813
TI  - Psychophysiological reactions in dental phobic patients with direct vs. indirect
      fear acquisition.
AB  - Dental phobic patients with reported traumatic experiences at onset of dental
      anxiety were compared to subjects with an indirect fear acquisition in their
      psychophysiological responses to video scenes showing dental procedures. It has
      been suggested that individuals with conditioned fear would respond with higher
      levels of physiological arousal in response to threat compared to subjects with
      indirect fear acquisition. Although the overall pattern indicates support for
      this hypothesis, subjects grouped on the basis of their reported fear-etiology
      did not statistically differ in recorded muscle tension, heart rate or skin
      conductance reactions to fear-provoking conditions.

PMID- 15157812
TI  - Vesicular glutamate transporter immunoreactivity in the central and peripheral
      endings of muscle-spindle afferents.
AB  - Expression of vesicular glutamate transporters (VGLUTs: VGLUT1, VGLUT2 and
      VGLUT3) in muscle spindle afferents was examined in rats. VGLUT1 immunoreactivity
      was detected in the sensory endings on the equatorial and juxta-equatarial
      regions of intrafusal fibers as well as in many axon terminals within lamina IX
      of the spinal cord. VGLUT1 might be expressed not only in the central axon
      terminals but also in the peripheral sensory endings of muscle-spindle afferents.

PMID- 15157814
TI  - "Air bag" organoleptic behavioral experiment for managing fear of oral malodor.
AB  - People suffering from the fear of oral malodor believe that they have halitosis,
      even though offensive oral malodor is absent. Management of such patients is
      challenging. A simple innovative technique, "air bag" breathing method can be
      used as a behavioral experiment to provide the patient with evidence that may
      disconfirm their pertinent belief. In this method air samples are collected in an
      odor free plastic bag from the patient and healthy volunteers and the patient
      blindly rates the odor quality of each sample.

PMID- 15157815
TI  - The relationship between experiential avoidance and the severity of
      trichotillomania in a nonreferred sample.
AB  - In this study 436 adults, who reported being diagnosed with trichotillomania
      (TTM), completed an anonymous survey examining the relationship between
      experiential avoidance (i.e., escape from or avoidance of unwanted thoughts or
      emotions) and TTM severity. Results showed a significant positive correlation
      between measures of experiential avoidance and TTM severity, indicating that more
      experientially avoidant individuals tended to exhibit more severe TTM. Subsequent
      analyses found that persons who scored higher on a measure of experiential
      avoidance reported more frequent and intense urges to pull, were less able to
      control their urges, and experienced more pulling-related distress than persons
      who were not experientially avoidant. Conversely, results also showed that
      individuals who were more experientially avoidant were no more likely to actually
      pull and were no less successful in actually stopping themselves from pulling
      than non-avoidant individuals. The results of this study suggest that
      experiential avoidance may be an important issue in understanding and possibly
      treating some persons with TTM.

PMID- 15157816
TI  - Towards a cognitive model and measure of dissociation.
AB  - Dissociation comprises a range of psychological processes, which have largely
      been the subject of psychodynamic discussion. Dissociative phenomena are for the
      most part unaddressed by cognitive theorists. Current measures are atheoretical
      and our understanding of dissociation has been hampered by the absence of clear
      psychological models. This paper describes a new cognitive model of dissociation
      and the development and validation of a theoretically based measure-the Wessex
      Dissociation Scale (WDS). The WDS has adequate internal consistency, shows
      convergent validity with the Dissociative Experiences Scale (DES-II), and is
      equivalent to the DES-II in its associations with severe psychopathology.
      However, the WDS has some advantages over the DES-II, in that it is sensitive to
      milder manifestations of dissociation, demonstrating links to less severe
      pathologies. The findings described here provide preliminary support for the
      usefulness of the cognitive model, and the varied consequences of dissociative
      processes. The clinical and research utility of the model and the scale are
      discussed.

PMID- 15157817
TI  - Factor structure of the Psychiatric Diagnostic Screening Questionnaire (PDSQ), a
      screening questionnaire for DSM-IV axis I disorders.
AB  - We examined the factor structure of the Psychiatric Diagnostic Screening
      Questionnaire (PDSQ), a 125-item self-report scale that screens for 15 of the
      most common Axis I psychiatric disorders for which patients seek treatment in
      outpatient settings. The sample consisted of 2440 psychiatric outpatients.
      Thirteen factors were extracted. Ten mapped directly onto the DSM-IV diagnosis
      for which they were designed and one represented suicidal ideation. The remaining
      two factors reflected closely related disorders: Panic Disorder/Agoraphobia, and
      Somatization/Hypochondriasis. A psychosis factor was not extracted. Overall, the
      factor structure of the PDSQ was consistent with the DSM-IV nosology upon which
      it was developed.

PMID- 15157819
TI  - Inflammatory bowel disease: causes and consequences.

PMID- 15157818
TI  - Encoding processes in social anxiety.
AB  - According to current theories, memory processes play an important role in the
      maintenance of social fears. However, the empirical evidence regarding memory
      processes in social anxiety is controversial, and little is known about specific
      memory processes, such as encoding. The present study employs a release from
      proactive interference (RPI) technique to explore encoding-related processes in
      social anxiety. Eighty-four high and low socially anxious college students
      participated in the RPI task. The main hypothesis was that RPI effects that
      involve socially threatening words are greater in high than in low socially
      anxious subjects. Contrary to this hypothesis, however, greater RPI effects were
      found in low rather than in high socially anxious subjects if a social threat
      dimension was encoded. This suggests that low socially anxious individuals show
      more specific encoding strategies of threatening information than high socially
      anxious individuals.

PMID- 15157820
TI  - Inflammatory bowel disease: a complex group of genetic disorders.
AB  - Inflammatory bowel disease (IBD) are complex genetic disorders resulting from the
      complex interplay between several genetic and environmental risk factors. The
      number of IBD genes is currently unknown but it is expected to be equal or higher
      to 8. None of these genes are expected to be neither necessary nor sufficient for
      disease development. Among the candidate genes investigated to date, only
      CARD15/NOD2 has been definitively associated with Crohn Disease (CD) but not
      Ulcerative Colitis (UC). This gene explains about 20% of the genetic
      predisposition to CD. Because it is involved in the innate immunity, it allows to
      speculate that CD is the result of a defect in host-bacteria interaction.
      However, it is not known if CD is caused by specific bacteria or the gut flora as
      a whole.

PMID- 15157821
TI  - Epidemiology of IBD during the twentieth century: an integrated view.
AB  - Current incidence figures on ulcerative colitis and Crohn's disease--presented in
      a recent multicenter study in Europe--are given, and differences in the frequency
      and clinical appearances of the two conditions are discussed. Trends in the
      frequency and clinical appearance of inflammatory bowel disease during the
      twentieth century are summarized, as well as the differences over time and from
      place to place. Correlations between age, sex, localization of disease and
      clinical symptoms are given. Risk of progression to more extensive disease in
      patients with proctitis is shown. Incidences of inflammatory bowel disease in
      childhood and among migrated ethnic groups are discussed. Survival and cancer
      risk among patients with ulcerative colitis and Crohn's disease are shown from
      long-term clinical epidemiological studies of well-defined patient groups. Trends
      in these important prognostic parameters over time are shown, as well as factors
      influencing prognosis of the diseases.

PMID- 15157822
TI  - Tobacco and IBD: relevance in the understanding of disease mechanisms and
      clinical practice.
AB  - Current smoking protects against ulcerative colitis and, after onset of the
      disease, improves its course, decreasing the need for colectomy. However, smoking
      increases the risk of developing Crohn's disease and worsens its course,
      increasing the need for steroids, immunosuppressants and reoperations. Smoking
      cessation aggravates ulcerative colitis and improves Crohn's disease. The effects
      of smoking are the sum of contradictory effects of various substances, including
      nicotine and carbon monoxide, and are modulated by gender, genetic background,
      disease location and activity, cigarette dose and nicotine concentration. Smokers
      with ulcerative colitis should not be discouraged from stopping smoking but
      encouraged to stop, to reduce their risk of cardiopulmonary tobacco-related
      diseases. In Crohn's disease, smoking cessation has become a major therapeutic
      goal, particularly in young women and in patients with ileal involvement. A large
      amount of supportive information, use of nicotine-replacement therapies and
      antidepressants, and individual counselling might aid the patient in quitting.

PMID- 15157823
TI  - Environmental risk factors (excluding tobacco and microorganisms): critical
      analysis of old and new hypotheses.
AB  - The increase in incidence in both ulcerative colitis and Crohn's disease during
      the 20th century has led to an abundance of different hypotheses on what sort of
      exposures are responsible. There has been a special focus on dietary factors, as
      well as on other exposures introduced on a population-based level, including fast
      food, cola drinks, toothpaste, antibiotics and oral contraceptives. The aim of
      this review is to critically assess the results from the different observational
      studies that have investigated these hypotheses, and also to propose research
      agendas that should be pursued in the future. The conclusion is that infectious
      exposures and early bacterial colonization, which are associated with better
      hygiene early in life and that influence immune function, and possibly oral
      contraceptives, remain the only exposures of interest for future research into
      the aetiology of ulcerative colitis and Crohn's disease.

PMID- 15157825
TI  - IBD: a family affair.
AB  - The recent molecular advances in the understanding of the genetics of
      inflammatory bowel disease (IBD) have their grounding in studies examining IBD
      within different family groups and populations. The risk of IBD is highest in
      first-degree relatives of an IBD proband but more distant relatives are also at
      increased risk. The risk is higher for relatives of a CD proband. The risks of
      developing IBD for 'high-risk' relatives might be as great as 1 in 3 but in
      general first-degree relatives have a 1 in 10-20 risk. Three recent systematic
      studies have identified a total of 326 European twin pairs to examine disease
      concordance rates. The derived heritability in Crohn's disease is greater than
      for many complex diseases and is currently under detailed examination. Strong
      concordance has been shown, in particular for disease type and disease location,
      in multiplex families and twin studies. More than 75% children are diagnosed with
      IBD at a younger age than their parents but true genetic anticipation appears
      unlikely.

PMID- 15157824
TI  - Specificities of inflammatory bowel disease in childhood.
AB  - In parallel with overall population trends, the incidence of paediatric
      ulcerative colitis (UC) has remained stable, whereas that of paediatric Crohn's
      disease (CD) has increased in recent decades. Still rare among preschool
      children, the incidence of both UC and CD rises steadily from middle childhood
      through adolescence. There is an unexplained preponderance of males with early
      onset CD, and an equal gender distribution in paediatric UC. Observations on the
      familiality of paediatric inflammatory bowel disease (IBD) suggest that genetic
      susceptibility is particularly important to disease pathogenesis in young
      patients. In comparison to adult-onset disease, childhood UC is usually extensive
      but the anatomic localization of paediatric CD varies, as in adults. UC manifests
      uniformly as bloody diarrhea whereas the symptomatology of paediatric CD is much
      more diverse. Linear growth impairment frequently complicates chronic intestinal
      inflammation in paediatric CD. Key contributing factors have been defined; better
      immunomodulatory therapy and emerging biologic agents will potentially reduce its
      prevalence.

PMID- 15157826
TI  - Genome scan analyses and positional cloning strategy in IBD: successes and
      limitations.
AB  - The past decade has witnessed a tremendous expansion of our knowledge-base of
      genetics of inflammatory bowel disease. To a large extent, this progress reflects
      the scientific innovation and impact of the human genome project, which has
      fueled many laboratory-based studies focusing on the molecular genetics of
      Crohn's disease and ulcerative colitis. The complementary strategies of genome
      wide linkage scanning and candidate gene analysis uncovered a number of genetic
      loci associated with IBD susceptibility. Notably, the identification of the IBD1
      and IBD5 loci is a major scientific discovery. Although many issues related to
      the function and expression of these genes await elucidation, there is a shared
      optimism that pivotal clinical applications will emerge from these
      investigations.

PMID- 15157827
TI  - Towards an understanding of the role of NOD2/CARD15 in the pathogenesis of
      Crohn's disease.
AB  - With the recent discovery of NOD2 as the first susceptibility gene linked with
      Crohn's disease, research is now focused on attempting to explain the biological
      role of NOD2 and how mutations can contribute to the development of this
      inflammatory disease. Biochemical studies have revealed that NOD2 is in fact a
      protein involved in the innate immune detection of bacterial products. More
      specifically, NOD2 recognizes a fragment of peptidoglycan, called muramyl
      dipeptide, that is found in the cell walls of both Gram-negative and Gram
      positive bacteria. This recognition event triggers a pro-inflammatory signalling
      cascade regulated by the transcription factor NF-kappa B. The complex cellular
      responses emanating from the interaction of NOD2 and its ligand are thought to
      touch on many aspects of immune function, including bacterial killing, cytokine
      release, stimulation and maturation of antigen-presenting cells, and the
      regulation of the adaptive immune response. Defining these NOD2-regulated
      responses, and how mutations in the gene encoding this protein disrupt these
      responses, will be key to understanding the pathogenesis of Crohn's disease.

PMID- 15157828
TI  - NOD2/CARD15: relevance in clinical practice.
AB  - So far, the relevance of NOD2/CARD15 genotyping for clinical practice is modest.
      The current data almost unanimously show that NOD2/CARD15 mutations in Crohn's
      disease are associated with small-bowel involvement. More studies are needed to
      determine whether NOD2/CARD15 mutations are also associated with a fibrostenotic
      behaviour of the disease. If CARD15 variants would predict a more aggressive
      disease course, then a more aggressive treatment is justified in these patients
      after NOD2/CARD15 genetic testing. It is not clear whether NOD2/CARD15 genotyping
      is helpful in differentiating indeterminate colitis patients. Although CARD15
      variants do not predict response to the TNF alpha monoclonal antibodies, the role
      of the gene in response to other drugs is not known. Finally, screening
      unaffected relatives of CD patients is not recommended until preventive
      strategies are available.

PMID- 15157830
TI  - Pharmacogenetics of inflammatory bowel disease.
AB  - The therapeutic efficacy and toxicity of many commonly employed drugs show
      interindividual variations that relate to several factors, including genetic
      variability in drug-metabolizing enzymes, transporters or targets. The study of
      the genetic determinants influencing interindividual variations in drug response
      is known as pharmacogenetics. The ability to identify, through preliminary
      genetic screening, the patients most likely to respond positively to a medication
      should facilitate the best choice of treatment for each patient; drugs likely to
      exhibit low efficacy or to give negative side-effects can be avoided. Among the
      medications used for inflammatory bowel disease, the best studied
      pharmacogenetically is azathioprine. The hematopoietic toxicity of azathioprine
      is due to single nucleotide polymorphisms in the thiopurine S-methyltransferase
      enzyme. Additionally, likely gene targets have been investigated to predict the
      response to glucocorticoids and infliximab, a monoclonal antibody against tumour
      necrosis factor that induces remission in approximately 30-40% of patients.
      However, no genetic predictor of response has been identified in either case.

PMID- 15157832
TI  - The regulation of thyroid function during normal pregnancy: importance of the
      iodine nutrition status.
AB  - The main change in thyroid function associated with the pregnant state is the
      requirement of an increased production of thyroid hormone that depends directly
      upon the adequate availability of dietary iodine and integrity of the glandular
      machinery. Physiologic adaptation takes place when the iodine intake is adequate,
      while this is replaced by pathologic alterations when there is a deficient iodine
      intake. Pregnancy acts typically, therefore, as a revelator of underlying iodine
      restriction. Iodine deficiency (ID) has important repercussions for both the
      mother and the fetus, leading to sustained glandular stimulation,
      hypothyroxinemia and goitrogenesis. Furthermore, because severe ID may be
      associated with an impairment in the psycho-neuro-intellectual outcome in the
      progeny-because both mother and offspring are exposed to ID during gestation (and
      the postnatal period), and because ID is still prevalent today in several
      European countries-it has been proposed already in the early 1990s that iodine
      supplements be given systematically to pregnant and breast-feeding women.
      Particular attention is required to ensure that pregnant women receive an
      adequate iodine supply, by administering multivitamin tablets containing iodine
      supplements, in order to achieve the ideal recommended dietary allowance of 200
      250 microg iodine/day.

PMID- 15157829
TI  - The contribution of HLA genes to IBD susceptibility and phenotype.
AB  - The human leukocyte antigen (HLA) region located on chromosome 6p encodes the
      highly polymorphic, classical class I and II genes essential for normal
      lymphocyte function; it also encodes a further 224 genes. Many early studies
      investigating this region were limited by small sample size, poor statistical
      methodology, population stratification and variable disease definition. Although
      more recent studies have improved study design, investigators are still
      challenged by the complex patterns of linkage disequilibrium across this gene
      dense region, and by the disease heterogeneity characteristic of all genetically
      complex disorders. However, a number of important observations have emerged from
      recent studies: (1) the HLA harbours gene(s) that determine susceptibility to
      colonic inflammation in both ulcerative colitis (UC) and Crohn's disease (CD);
      (2) most of the specific associations with UC and CD appear to differ; (3)
      associations between different ethnic groups differ; (4) markers in the HLA might
      predict the course of disease and the development of complications, notably the
      extraintestinal manifestations of disease.

PMID- 15157833
TI  - Female infertility and the thyroid.
AB  - Difficulty to conceive or subfertility constitutes a major psychological burden.
      Assisted reproductive technology changed significantly the outcome of couples
      faced with subfertility. These techniques consequently increased tremendously our
      understanding of the mechanisms underlying reproductive failure and opened new
      perspectives for future interventions, not only to increase cumulative conception
      rates after ART, but also spontaneous pregnancy rates. Thyroid dysfunction
      adversely affects fertility. Many studies imply a role for immunology, including
      thyroid autoimmunity in conception failure. In this review we attempt to update
      the available information on the adverse effect of thyroid dysfunction and/or
      thyroid autoimmunity on subfertility and we propose a rationale for testing and
      potential treatment options.

PMID- 15157835
TI  - Male reproductive function in relation with thyroid alterations.
AB  - Despite the high prevalence of thyroid diseases in the general population, the
      impact of the latter on male reproductive function has been the subject of only a
      few well-controlled clinical studies. Hyperthyroidism appears to cause
      alterations in the sex steroid hormone metabolism as well as in spermatogenesis
      and fertility. Sperm motility is mainly affected. These abnormalities reverse
      after restoration of euthyroidism. The effects of hypothyroidism on male
      reproduction appear to be more subtle than those of hyperthyroidism and
      reversible. Severe juvenile hypothyroidism may be associated with precocious
      puberty. Hypothyroidism in adults is associated with disturbances in the sex
      steroid hormone metabolism as well as infertility, although available data
      concerning the latter are scarce. Radioiodine ((131)I) treatment for
      dfferentiated thyroid cancer may cause transient impairment of testicular
      function Gonadal damage may be cumulative in those requiring multiple
      administrations and sperm banking should be considered in such patients.

PMID- 15157834
TI  - Thyroid autoimmunity and the risk of miscarriage.
AB  - Approximately one-third of all pregnancies end in miscarriage. The etiology of
      recurrent abortion remains unknown in approximately 50% of all women. In the
      early 1990s it was discovered that unselected euthyroid women who present with
      thyroid antibodies (thyroid peroxidase and thyroglobulin) in the first trimester
      of pregnancy have a two-four-fold increase in their miscarriage rates. The
      majority of studies investigating women with recurrent abortion have also found a
      significant increase in thyroid antibody positivity compared with controls.
      Although the etiology of miscarriage in thyroid antibody women remains unknown,
      recent data have revealed a potential direct effect of thyroglobulin antibodies
      on pregnancy loss in a murine model. Uncontrolled studies assessing the effect of
      levothyroxine on decreasing the miscarriage rate in euthyroid antibody positive
      women, have demonstrated a decreased miscarriage rate.

PMID- 15157836
TI  - Self-recognition and the role of fetal microchimerism.
AB  - The course and severity of the autoimmune thyroid diseases (AITD) is known to be
      influenced by pregnancy as evidenced by disease suppression during pregnancy and
      initiation, or exacerbation, of disease postpartum. AITD is also known to affect
      both fertility and pregnancy outcome as evidenced by increased fetal loss.
      However, the precise mechanisms of this influence have not been fully understood.
      Here we have reviewed the mechanisms of self-recognition thought to be active in
      AITD and we have included recent information on the potential role of fetal
      microchimerism (exposure of paternal antigen to the mother during and after
      pregnancy).

PMID- 15157837
TI  - Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal
      aspects.
AB  - Hypothyroidism during pregnancy is associated with adverse outcomes that can be
      ameliorated or prevented by adequate therapy with thyroxine. Currently, there are
      no guidelines for universal screening for thyroid dysfunction in pregnant women
      or in women of reproductive age. Therefore, it is important to recognize those
      groups of women who may be at higher risk for development of hypothyroidism so
      that serum TSH testing may be performed with appropriate initiation of thyroxine
      therapy. In addition, the thyroxine therapy of women with established
      hypothyroidism should be optimized prior to conception and during pregnancy when
      the thyroxine dosage requirement generally increases early in gestation. The
      diverse etiologies of maternal hypothyroidism may require different increments in
      thyroxine dose during pregnancy, and generally the postpartum dosage requirement
      returns to pre-pregnancy levels.

PMID- 15157839
TI  - Physiological and pathological aspects of the effect of human chorionic
      gonadotropin on the thyroid.
AB  - Human chorionic gonadotropin (hCG) is a glycoprotein hormone that has structural
      similarity to TSH. At the time of the peak hCG levels in normal pregnancy, serum
      TSH levels fall and bear a mirror image to the hCG peak. This reduction in TSH
      suggests that hCG causes an increased secretion of T4 and T3. Women with
      hyperemisis gravidarum often have high hCG levels that cause transient
      hyperthyroidsm. In the vast majority of such patients, there will be spontaneous
      remission of the increased thyroid function when the vomiting stops in several
      weeks. When there are clinical features of hyperthyroidism, it is be reasonable
      to treat with antithyroid drugs or a beta-adrenergic blocker, but treatment is
      rarely required beyond 22 weeks of gestation. Hyperthyroidism or increased
      thyroid function has been reported in many patients with trophoblastic tumors,
      either hydatiditform mole or choriocarcinoma. The diagnosis of hydatidiform mole
      is made by ultrasonography that shows a 'snowstorm' appearance without a fetus.
      Hydatidiform moles secrete large amounts of hCG proportional to the mass of the
      tumor. The development of hyperthyroidism requires hCG levels of >200 U/ml that
      are sustained for several weeks. Removal of the mole cures the hyperthyroidism.
      There have been many case reports of hyperthyroidism in women with
      choriocarcinoma and high hCG levels. The principal therapy is chemotherapy,
      usually given at a specialized center. With effective chemotherapy, long-term
      survival exceeds 95%. A unique family with recurrent gestational hyperthyroidism
      associated with hyperemesis gravidarum was found to have a mutation in the
      extracellular domain of the TSH receptor that made it responsive to normal levels
      of hCG.

PMID- 15157838
TI  - Maternal thyroid hormones early in pregnancy and fetal brain development.
AB  - During the last few decades our understanding of the possible role of thyroid
      hormones during brain development has increased and contributed to resolve
      previously discordant hypotheses, although much remains to be clarified. Thyroid
      hormones of maternal origin are present in the fetal compartment, despite the
      very efficient uterine-placental 'barrier', necessary to avoid potentially toxic
      concentrations of free T4 and T3 from reaching fetal tissues before they are
      required for development. T3 remains low throughout pregnancy, whereas FT4 in
      fetal fluids increases rapidly to adult levels, and is determined by the maternal
      availability of T4. It is present in embryonic fluids 4 weeks after conception,
      with FT4 steadily increasing to biologically relevant values. T3, generated from
      T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly
      bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are
      important for the spatial and temporal regulation of T3 bioavailability, tailored
      to the differing and changing requirements of thyroid hormone-sensitive genes in
      different brain structures, but other regulatory mechanism(s) are likely to be
      involved. Maternal transfer constitutes a major fraction of fetal serum T4, even
      after onset of fetal thyroid secretion, and continues to have an important
      protective role in fetal neurodevelopment until birth. Prompt treatment of
      maternal hypothyroidism, identified by increased TSH, is being advocated to
      mitigate a negative effect on the woman and her child. However, even a moderate
      transient period of maternal hypothyroxinemia at the beginning of rat
      neurogenesis disrupts neuronal migration into cortical layers. These findings
      reinforce the epidemiological evidence that early maternal hypothyroxinemia-when
      neuronal migratory waves are starting-is potentially damaging for the child.
      Detection of an inappropiate first trimester FT4 surge that may not result in
      increased TSH, may be crucial for the prevention of learning disabilities in a
      significant number of unborn children.

PMID- 15157840
TI  - Hyperthyroidism in pregnancy.
AB  - Graves' disease may complicate the course of pregnancy; pregnancy on the other
      hand may alter the natural course of the disease. It is imperative for women of
      childbearing age affected by the disease to be informed about the potential
      maternal and fetal problems if the condition is not properly managed.
      Preconception control in women with diabetes has resulted in a dramatic decrease
      in the number of perinatal complications. The same approach should be encouraged
      for women with thyroid diseases. Ideally, the women suffering from
      hyperthyroidism or any other thyroid disease should be metabolically compensated
      at time of conception-the need for contraception until the disease is controlled
      should be openly discussed. A multidisciplinary approach by a health care team is
      of paramount importance during pregnancy, with the involvement of the
      obstetrician, perinatologist, endocrinologist, neonatologist, pediatrician and
      anesthesiologist. In many situations the assistance of social workers,
      nutritionists, and other health care professionals may be needed. The future
      mother and her family should be aware of the potential complications for both
      mother and her offspring if proper management guidelines are not carefully
      followed.

PMID- 15157842
TI  - Postpartum thyroiditis.
AB  - Postpartum thyroiditis (PPT) is the occurrence, in the postpartum period, of
      transient hyperthyroidism and/or transient hypothyroidism, with most women
      returning to the euthyroid state by 1 year postpartum. The prevalence of PPT
      varies from 1.1 to 16.7%, with a mean prevalence of 7.5%. Women with type I
      diabetes mellitus have a three-fold increase in the prevalence of PPT. PPT is an
      autoimmune disorder which is a transient form of Hashimoto's thyroiditis
      occurring postpartum as a consequence of the immunologic flare following the
      immune suppression of pregnancy. Women experience symptoms in both the
      hyperthyroid and hypothyroid phase, but the association between PPT and
      postpartum depression remains undefined. Approximately 25% of women with a
      history of PPT will develop permanent hypothyroidism in the ensuing 10 years.
      Treatment for the hyperthyroid phase, when required, is a short dose of beta
      blockers. Women with a TSH greater than 10 mU/l, or between 4 and 10 mU/l with
      symptoms or attempting pregnancy, require thyroid hormone replacement. Whether or
      not to screen for PPT remains controversial.

PMID- 15157844
TI  - EU clinical trials directive: 0% inspiration, 100% perspiration?

PMID- 15157841
TI  - Fetal and neonatal thyroid function in relation to maternal Graves' disease.
AB  - The abundance of published data on the neonatal effects of maternal Graves'
      disease (GD) contrasts with the paucity of information on fetal effects. In our
      yet unpublished study, we prospectively studied 72 pregnant women with a history
      of Graves' disease. Fetal ultrasonography was done at 22 and 32 weeks of
      gestational age. Fetal goiter was found at 32 weeks in 11 of the fetuses of the
      41 mothers with positive TSH-receptor antibodies and/or antithyroid treatment and
      in none of the fetuses of the 31 other mothers. In the 11 fetuses with goiter,
      ultrasound findings (thyroid Doppler and bone maturation), fetal heart rate, and
      maternal antibody and antithyroid drug status effectively discriminated between
      hypothyroidism (n=7) and hyperthyroidism (n=4). One fetus with hyperthyroidism
      died in utero at 35 weeks from heart failure. Treatment was successful in the ten
      other fetuses. One fetus without goiter had moderate hypothyroidism at birth.
      This study showed that it is of the utmost importance to have the fetal thyroid
      scrutinized by an expert ultrasonographist and to have team work with
      obstetricians and paediatric endocrinologists in pregnant mothers with GD. This
      allowed us to accurately determine fetal thyroid status and to adapt the
      treatment in mothers successfully. Fetal hyperthyroidism does exist and needs an
      appropriate aggressive treatment.

PMID- 15157845
TI  - IMAGES and FAST-MAG: magnesium for acute ischaemic stroke.

PMID- 15157846
TI  - The telltale scan: APOE epsilon4 in multiple sclerosis.

PMID- 15157847
TI  - CGRP antagonists in the acute treatment of migraine.

PMID- 15157848
TI  - Obstructive sleep apnoea and stroke.
AB  - Many patients with stroke have concomitant sleep apnoea, which can affect
      recovery potential. Although stroke can lead to the development of sleep
      disordered breathing, the current evidence suggests that sleep-disordered
      breathing may function as a risk factor for stroke. In this review, we focus on
      the association between obstructive sleep apnoea and stroke reviewing both the
      epidemiological data with respect to causation and the biological data, which
      explores pathogenesis. There is convincing evidence to believe that sleep apnoea
      is a modifiable risk factor for stroke; however, prospective studies are needed
      to establish the cause-and-effect relationship.

PMID- 15157849
TI  - An active and socially integrated lifestyle in late life might protect against
      dementia.
AB  - The recent availability of longitudinal data on the possible association of
      different lifestyles with dementia and Alzheimer's disease (AD) allow some
      preliminary conclusions on this topic. This review systematically analyses the
      published longitudinal studies exploring the effect of social network, physical
      leisure, and non-physical activity on cognition and dementia and then summarises
      the current evidence taking into account the limitations of the studies and the
      biological plausibility. For all three lifestyle components (social, mental, and
      physical), a beneficial effect on cognition and a protective effect against
      dementia are suggested. The three components seem to have common pathways, rather
      than specific mechanisms, which might converge within three major aetiological
      hypotheses for dementia and AD: the cognitive reserve hypothesis, the vascular
      hypothesis, and the stress hypothesis. Taking into account the accumulated
      evidence and the biological plausibility of these hypotheses, we conclude that an
      active and socially integrated lifestyle in late life protects against dementia
      and AD. Further research is necessary to better define the mechanisms of these
      associations and better delineate preventive and therapeutic strategies.

PMID- 15157850
TI  - Oestrogen and attacks of migraine with and without aura.
AB  - During women's reproductive years, migraine is three times more common than in
      men of a similar age. Although this female preponderance is commonly assumed to
      be associated with the additional trigger of fluctuating sex hormones of the
      menstrual cycle, few studies have been done to confirm or refute this. This
      review is confined to the relation between oestrogen and attacks of migraine. The
      evidence for an association between oestrogen "withdrawal" and attacks of
      migraine without aura is presented, as well as evidence for an association
      between high oestrogen states and attacks of migraine with aura. Only clinical
      data are presented here.

PMID- 15157851
TI  - Disease modification in Parkinson's disease.
AB  - Several separate gene mutations have now been identified in familial Parkinson's
      disease and important environmental influences modulating risk for the idiopathic
      form of the disease have also been recognised. These insights have provided
      important clues in the development of disease modifying therapies. Some compounds
      have already been shown to potentially delay disease progression in early
      clinical trials. The most important challenge, particularly for those drugs that
      might have a symptomatic effect, is defining appropriate markers that will
      confirm a neuroprotective effect.

PMID- 15157852
TI  - Are statins a treatment option for multiple sclerosis?
AB  - BACKGROUND: Treatment options for multiple sclerosis (MS) are limited. The
      immunomodulatory drugs interferon beta and glatiramer acetate are only partly
      effective in reducing the relapse rate, slowing disease progression, and
      diminishing the number and volume of lesions on MRI. Mitoxantrone is an
      immunosuppressant approved for the treatment of active forms of relapsing
      remitting or secondary progressive MS, but is dose-limited owing to its potential
      cardiotoxicity. Thus, identifying new effective therapeutic options with few side
      effects is highly desirable. RECENT DEVELOPMENTS: Evidence has emerged that
      statins, which are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase,
      have immunomodulatory effects. Recent reports showed that statins prevent and
      reverse chronic and relapsing experimental autoimmune encephalomyelitis, an
      animal model of MS. Furthermore, in vitro experiments with human immune cells
      have shown an immunomodulatory profile of statins comparable to that of
      interferon beta. An open label clinical trial of simvastatin for MS revealed a
      significant decrease in the number and volume of new MRI lesions and a favourable
      safety profile. WHERE NEXT?: The obvious advantage of statins over existing MS
      therapies is their oral route of dosing. Statins might be beneficial for MS
      patients as monotherapy or as an add-on to established disease modifying drugs.
      As the evidence of the benefit of statins in MS is currently insufficient, large
      controlled clinical trials are needed. The first of these trials is about to
      start.

PMID- 15157853
TI  - How the brain repairs itself: new therapeutic strategies in inflammatory and
      degenerative CNS disorders.
AB  - In the early 20th century, seminal work by Tello and Cajal showed that the CNS
      has the ability to regenerate itself after injury. In the most recent years, this
      pivotal observation has been rejuvenated by detailed in vitro and in vivo
      evidence supporting the idea of an innate self-maintenance programme to sustain
      brain homoeostasis and repair. These observations support the idea that chronic
      inflammatory and degenerative disorders of the brain might result from defective
      repair mechanisms rather than uncontrollable pathogenetic events. Investigation
      of the molecular and cellular events sustaining intrinsic brain-repair mechanisms
      and a better understanding of why they fail over time in chronic disorders might,
      therefore, provide an attractive conceptual framework within which to develop new
      and efficacious therapies for neurological diseases.

PMID- 15157854
TI  - Pushing the envelope.

PMID- 15157855
TI  - Effect of Fenton-like oxidation on enhanced oxidative degradation of para
      chlorobenzoic acid by ultrasonic irradiation.
AB  - Sonolysis, Fenton-like oxidation (FeOOH-H2O2), and a combination of the two
      processes were used to facilitate the degradation of para-chlorobenzoic acid (a
      model compound for free radical mediated reactions). The objective of this study
      was to investigate the effect of FeOOH and H2O2 dosages on the degradation of
      para-chlorobenzoic acid (p-CBA) using ultrasound/FeOOH-H2O2. The oxidation rate
      of p-CBA was measured at various concentrations of H2O2 and FeOOH particles and
      pH conditions. pH's below the pKa of p-CBA (3.98), showed significantly better
      degradation of p-CBA than at higher values from 5 to 9. The rates of degradation
      of p-CBA by FeOOH-H2O2 were enhanced in the presence of ultrasound. The first
      order rate constant, k for p-CBA degradation by ultrasound was 4.5 x 10(-3) min(
      1), and in the presence of FeOOH-H2O2 this was found to be substantially faster
      (1.54 x 10(-2) min(-1)). The observed rate enhancements for the degradation of p
      CBA can be attributed primarily to the continuous cleaning and chemical
      activation of the FeOOH surfaces by acoustic cavitation and the accelerated mass
      transport rates of reactants and products between the solution phase and the
      FeOOH surface. This new process provides a viable alternative to existing
      oxidation technologies.

PMID- 15157857
TI  - Treatment of transplanted adriamycin-resistant ovarian cancers in mice by
      combination of adriamycin and ultrasound exposure.
AB  - Ovarian cancer models were established in cyclophosphamide immunosuppressed mice
      by subrenal capsular cell fibrin clot transplantation. SKOV3 cancers were treated
      by adriamycin alone, or adriamycin combined with ultrasound exposure. SKOV3/ADR
      cancers were treated with adriamycin, as well as verapamil and insonation were
      administrated alone or concurrently. The results were: (1) Insonation alone could
      not suppress growth of tumours. (2) In SKOV3 cancers, ultrasound exposure
      potentiated the efficiency of adriamycin. (3) In SKOV3/ADR cancers, insonation
      reversed adriamycin resistance, but verapamil was not effective and no synergism
      existed between it and ultrasound. These findings revealed that ultrasound
      exposure enhanced the efficiency of adriamycin to both chemosensitive and
      chemoresistant ovarian cancers in vivo. Mechanisms were discussed.

PMID- 15157856
TI  - High power ultrasound effects on lipid oxidation of refined sunflower oil.
AB  - The effects of high power ultrasound treatment (20 kHz) on some components of
      refined sunflower oil were studied in order to verify if and to what extent
      modifications in the lipidic fraction can occur. Traditional parameters including
      free acidity, total polar compounds, peroxide value, and conjugated dienes
      concentration were determined in refined sunflower oil samples before,
      immediately after the ultrasonic treatment and during storage. Differences
      between treated and untreated samples were detected only for peroxide values
      (PV). The PV increased from 5.38 meq. O2/kg oil for untreated oil to 6.33 meq.
      O2/kg oil for sunflower oil sonicated (20 kHz; 150 W; 2 min). The fatty acid
      composition was obtained by high resolution gas chromatography. No significant
      changes were observed regarding the decrease in fatty acid composition before and
      immediately after the treatment. Regarding the volatile fraction, some off
      flavour compounds for example hexanal and limonene resulting from the ultrasonic
      degradation of sunflower oil were identified by gas chromatography coupled to
      mass spectrometry (GC-MS).

PMID- 15157858
TI  - A sonochemical method for the selective synthesis of alpha-HgS and beta-HgS
      nanoparticles.
AB  - A novel sonochemical method for the selective synthesis of alpha-HgS (cinnabar)
      and beta-HgS (metacinnabar) nanoparticles in aqueous solutions is reported in
      this paper. alpha-HgS and beta-HgS nanoparticles have been selectively prepared
      by choosing sodium thiosulfate and thiourea as the sulfur source respectively. To
      study the crystalline structure, size, morphology and composition of the
      products, characterization techniques including X-ray powder diffraction,
      transmission electron microscopy, selected area electron diffraction, X-ray
      photoelectron spectroscopy and energy-dispersive X-ray analysis are employed. The
      optical properties of the nanoparticles are investigated by UV-visible absorption
      spectroscopic measurements. The direct band gap of the as-prepared alpha-HgS
      nanoparticles with an average size of 12 nm is calculated to be 2.8 eV according
      to the absorption spectrum. In the case of the beta-HgS nanoparticles with an
      average size of 13 nm, a broad absorption peak is observed in the UV-visible
      absorption spectrum, which can be ascribed to the special surface state of this
      sample. Probable mechanisms for the sonochemical formation of alpha-HgS and beta
      HgS nanoparticles in aqueous solutions are presented. The optimum pH value of the
      stock solutions and the effect of sonication time on the particle size are also
      investigated.

PMID- 15157859
TI  - Preparation of polyacrylamide and gamma-zirconium phosphate nanocomposites by
      intercalative polymerization.
AB  - A new inorganic-organic nanocomposite of polyacrylamide (PAM) and gamma-zirconium
      phosphate (gamma-ZrP) was prepared by intercalative polymerization. Intercalation
      of acrylamide (AM) monomer in gamma-ZrP was investigated by sonochemical and
      refluxing methods. High-intensity ultrasound does not induce the polymerization
      of AM but enhances greatly the intercalation rate. On the other hand, ultrasound
      also enhanced hydrolyzation of -CONH2 and shrinkage of PAM gel. The interlayer
      distance of AM-intercalated gamma-ZrP is 16.4 A. The polymerization and
      intercalation of AM occurred nearly at the same time by refluxing method. The
      same gamma-ZrP/PAM nanocomposites were obtained with (NH4)2S2O8 treatment.

PMID- 15157860
TI  - Reduction of selenious acid induced by ultrasonic irradiation--formation of Se
      nanorods.
AB  - Single crystalline Selenium nanorods are formed via the reduction of selenious
      acid induced by ultrasonic irradiation. The products were characterized by XRD,
      TEM and ED techniques. The possible mechanism for the formation of selenium
      nanorods was discussed.

PMID- 15157861
TI  - Sonochemistry of antitumor quinones in argon-saturated aqueous solutions:
      enhanced ferricytochrome c reduction.
AB  - Sonolysis of argon-saturated aqueous antitumor quinone solutions resulted in an
      enhancement in ferricytochrome c (Cyt c) reduction. Partial inhibition of these
      reduction enhancements by addition of superoxide dismutase evidences the
      production of superoxide ions. No correlation between quinone hydrophobicity or
      redox potential is observed in the extent of Cyt c reduction. The semiquinone of
      the parent quinone as well as other quinone-derived reductants are proposed as
      the electron shuttle intermediates which reduce Cyt c.

PMID- 15157862
TI  - Evidence for liquid phase reactions during single bubble acoustic cavitation.
AB  - We extended the recent experiment by Lepoint et al. [Sonochemistry and
      Sonoluminescence, NATO ASI Series, Series C 524, Kluwer Academic Publishers,
      Dordrecht/Boston/London, 1999, p. 285], involving a so-called single bubble
      sonochemistry process, to a three-phase system. We have found experimental
      evidence that a single cavitating bubble can activate the oxidation of I- ions
      after the injection of a CCl4 liquid drop in the bubble trapping apparatus. The
      solvent drop (CCl4 is almost water insoluble) is pushed towards the bubble
      position and forms a thin film on the bubble surface. When the acoustic pressure
      drive is increased above 100 kPa, the three-phase system gives rise to a dark
      filament, indicating the complexation reaction between starch (added to the water
      phase) and I2. I2 species is the product of surface reactions involving bubble
      induced decomposition of CCl4. Further increase of the acoustic drive causes the
      thin CCl4 film to separate from the bubble and stops I2 production. The study of
      the chemical activity of this three-phase system could give new advances on
      dynamics of the bubble collapse.

PMID- 15157863
TI  - Ultrasound enhancement of biocide efficiency.
AB  - In order to take account of the likely increase in costs of biocides in the light
      of increasing legislation and concern for the environment, there is a need to
      maximise the efficiency of biocides for the control of biofouling. The use of
      ultrasound in conjunction with biocides offers such an opportunity. Tests have
      been carried out using ultrasound generated at 20 kHz in conjunction with the
      oxidising biocide ozone, in a laboratory pilot plant, to investigate the effects
      of mutuality. The preliminary results reported in this paper suggest that the
      combined effect of ultrasound and the biocide is better than either separately
      employed. Clearly substantially more work is required in order to maximise
      effectiveness for minimum cost.

PMID- 15157864
TI  - Ultrasonically induced phthalocyanine degradation: decolouration vs. metal
      release.
AB  - The ultrasonically induced degradations of nickel(II) 2,9,16,23-tetraphenoxy-29H,
      31H-phthalocyanine and vanadyl 2,9,16,23-tetraphenoxy-29H, 31H-phthalocyanine in
      a biphasic system consisting of chloroform and water are investigated.
      Decolourisation of the organic phase containing the metallo-phthalocyanines is
      found to occur rapidly (approximately minutes for 8 ml of ca. 5 microM solution).
      Analysis of the aqueous solute via ICP-OES, reveals significant amounts of the
      released nickel ultimately transfers into the aqueous phase but at a rate much
      slower than that of decolourisation, whereas the vanadium remains within the
      organic phase suggesting only partial degradation despite efficient
      decolourisation.

PMID- 15157865
TI  - Improved wastewater disinfection by ultrasonic pre-treatment.
AB  - The objective of our work is to evaluate the scientific and economic potential of
      US application as a pre-treatment step in combination with UV to optimise the
      disinfection process of wastewaters. Ultrasound application of 20 s at low
      density of 30 W/l changed the particle size distribution (PSD) of the samples,
      the mean particle diameter dropped from 70 to 11 microm. Generally it is assumed
      that bioparticles bigger than 50 microm are difficult to disinfect by UV. We
      observed that the relevant particle size range >50 microm in samples taken from
      the primary clarifier was reduced by at least three-quarters by low ultrasound
      doses. As expected, these changes in PSD notably effect the disinfection
      efficiency of UV. Whereas UV treatment of secondary clarifier's effluents alone
      led to a reduction of fecal coliforms by 2.5 log units, pre-treatment by
      sonication (only 5 s at densities of 50 and 310 W/l) clearly enhanced the
      disinfection efficiency: reductions of CFU (colony forming unit) concentration
      now ranged between 3.3 and 3.7 log units. We noticed an influence of the
      bacteria's morphology on the disinfection efficiency of the combined process (US
      plus UV). Gram-positive streptococci seem less vulnerable to ultrasound exposure
      than thinner-walled gram-negative bacteria like the entire group of coliforms.
      The application of an ultrasound step might be also useful in terms of cost
      effectiveness. In our lab-scale tests 30 s of UV treatment alone were required to
      reduce the number of fecal coliforms by 3.7 log units. When applied in
      combination, 5 s of ultrasonic followed by only 5 s of UV irradiation had the
      same result and energy consumption was only 43%.

PMID- 15157866
TI  - Affinium Pharmaceuticals, Inc.: structure-guided drug discovery.

PMID- 15157867
TI  - Hydra Biosciences: inducing nature's regenerative power.

PMID- 15157868
TI  - A hot spot for protein kinase inhibitor sensitivity.
AB  - ATP binding site-directed protein kinase inhibitors are potent weapons in the war
      on cancer. However, specific mutations at an inhibitor-sensitivity "hot spot" can
      render these molecules ineffective. In this issue of Chemistry & Biology, Daub
      and coworkers have used an array of known kinase inhibitors to systematically
      characterize the desensitizing effects of hot spot mutations.

PMID- 15157869
TI  - Recombination of fragmented proteins.
AB  - Directed evolution is a powerful method for generating novel molecules with
      desirable properties. In developing a new sensor to screen for protein-protein
      interactions, Tafelmeyer et al. report a clever strategy to evolve heterodimeric
      "split proteins" from a monomer in this issue of Chemistry & Biology.

PMID- 15157870
TI  - Target identification in chemical genetics: the (often) missing link.

PMID- 15157871
TI  - Chemical dimerizers and three-hybrid systems: scanning the proteome for targets
      of organic small molecules.
AB  - The integration of technological advances in areas as diverse as chemical
      biology, proteomics, genomics, automation, and bioinformatics has led to the
      emergence of novel screening paradigms for analyzing the molecular basis of drug
      action. This review summarizes recent advances in three-hybrid technologies and
      their application to the characterization of small molecule-protein interactions
      and proteome-wide identification of drug receptors.

PMID- 15157872
TI  - Genetic and genomic approaches to identify and study the targets of bioactive
      small molecules.
AB  - Natural and synthetic bioactive small molecules form the backbone of modern
      therapeutics. These drugs primarily exert their effect by targeting cellular host
      or foreign proteins that are critical for the progression of disease. Therefore,
      a crucial step in the process of recognizing valuable new drug leads is
      identification of their protein targets; this is often a time consuming and
      difficult task. This report is intended to provide a comprehensive review of
      recent developments in genetic and genomic approaches to overcome the hurdle of
      discovering the protein targets of bioactive small molecules.

PMID- 15157873
TI  - Phosphoinositide signaling; from affinity probes to pharmaceutical targets.
AB  - Lipid signaling by phosphoinositides (PIP(n)s) involves an array of proteins with
      lipid recognition, kinase, phosphatase, and phospholipase functions.
      Understanding PIP(n) pathway signaling requires identification and
      characterization of PIP(n)-interacting proteins. Moreover, spatiotemporal
      localization and physiological function of PIP(n)-protein complexes must be
      elucidated in cellular and organismal contexts. For protein discovery to
      functional elucidation, reporter-linked phosphoinositides or tethered PIP(n)s
      have been essential. The phosphoinositide 3-kinase (PI 3-K) signaling pathway has
      recently emerged as an important source of potential "druggable" therapeutic
      targets in human pathophysiology in both academic and pharmaceutical
      environments. This review summarizes the chemistry of PIP(n) affinity probes and
      their use in identifying macromolecular targets. The process of target validation
      will be described, i.e., the use of tethered PIP(n)s in determining PIP(n)
      selectivity in vitro and in establishing the function of PIP(n)-protein complexes
      in living cells.

PMID- 15157874
TI  - The flip side: Identifying small molecule regulators of nuclear receptors.
AB  - Members of the nuclear hormone receptor superfamily function as ligand-activated
      transcription factors to regulate genetic networks controlling cell growth and
      differentiation, inflammatory responses, and metabolism. The ability to modulate
      nuclear receptor-dependent gene expression with small molecules has made the
      superfamily a favored target for drug discovery. Not surprisingly, small
      molecules that regulate receptor activity are currently used to treat a number of
      human disorders. Over the last 10 years, the availability of a common platform of
      functional assays suitable for any nuclear receptor has facilitated the
      identification of endogenous and synthetic ligands that have been used as tools
      to uncover previously unanticipated endocrine signaling pathways. Recent progress
      in understanding the molecular basis for ligand-dependent gene regulation
      suggests that a new era of "designer" ligands with tissue- and/or gene-selective
      activity will quickly be upon us.

PMID- 15157875
TI  - Identification of a small molecule that inhibits herpes simplex virus DNA
      Polymerase subunit interactions and viral replication.
AB  - The interaction between the catalytic subunit Pol and the processivity subunit
      UL42 of herpes simplex virus DNA polymerase has been characterized structurally
      and mutationally and is a potential target for novel antiviral drugs. We
      developed and validated an assay for small molecules that could disrupt the
      interaction of UL42 and a Pol-derived peptide and used it to screen approximately
      16,000 compounds. Of 37 "hits" identified, four inhibited UL42-stimulated long
      chain DNA synthesis by Pol in vitro, of which two exhibited little inhibition of
      polymerase activity by Pol alone. One of these specifically inhibited the
      physical interaction of Pol and UL42 and also inhibited viral replication at
      concentrations below those that caused cytotoxic effects. Thus, a small molecule
      can inhibit this protein-protein interaction, which provides a starting point for
      the discovery of new antiviral drugs.

PMID- 15157876
TI  - New aminocoumarin antibiotics formed by a combined mutational and chemoenzymatic
      approach utilizing the carbamoyltransferase NovN.
AB  - Five new aminocoumarin antibiotics were produced by a combined mutational and
      chemoenzymatic approach. For this purpose, the 3"-carbamoyltransferase NovN from
      the novobiocin producer Streptomyces spheroides was overexpressed in the
      heterologous host S. lividans as an N-terminal His(6) fusion protein and purified
      by nickel affinity chromatography. Five different 3"-unsubstituted aminocoumarin
      derivatives were isolated from mutants of the clorobiocin producer S.
      roseochromogenes, carrying single or multiple gene defects. All five compounds
      were readily accepted as substrates by NovN, and the 3"-carbamoylated products
      were isolated on a preparative scale. Their structures were elucidated by (1)H
      NMR and mass spectroscopy, and their inhibitory activity on gyrase in vitro as
      well as their antibacterial activity was determined. The results give further
      insight into the structure-activity relationships of aminocoumarin antibiotics.

PMID- 15157877
TI  - Taxol biosynthesis: Molecular cloning and characterization of a cytochrome P450
      taxoid 7 beta-hydroxylase.
AB  - Biosynthesis of the anticancer drug Taxol in yew species involves eight
      cytochrome P450-mediated oxygenations and four coenzyme A-dependent acylations of
      the diterpenoid core. A family of cytochrome P450 genes, obtained from a yew cell
      cDNA library, were functionally expressed and screened with taxusin (taxa
      4(20),11(12)-dien-5 alpha,9 alpha,10 beta,13 alpha-tetraol tetraacetate) as a
      surrogate substrate. One clone converted this substrate to an oxygenated
      derivative that was identified as 7 beta-hydroxytaxusin. The structure and
      properties of this 7 beta-hydroxylase are similar to those of other taxoid
      hydroxylases. Kinetic and binding assays indicated selectivity of the 7 beta
      hydroxylase for polyoxygenated and acylated taxoid substrates, an observation
      consistent with the operation of this enzyme in the central portion of the Taxol
      biosynthetic pathway. Although the 7 beta-hydroxyl of Taxol is not essential for
      antimitotic activity, this functional group provides a convenient means for
      preparing taxoid derivatives.

PMID- 15157878
TI  - An amphotericin B-ergosterol covalent conjugate with powerful membrane
      permeabilizing activity.
AB  - Amphotericin B-sterol conjugates were synthesized and examined for their membrane
      permeabilizing activity. Ergosterol and cholesterol, each connected with
      amphotericin B via an ethylenecarbamate or hexamethylenecarbamate linker, were
      examined by K(+) flux assays using liposomes and by single-channel recording
      across phospholipid membrane. Among four conjugates tested, AmB-ergosterol
      bearing an ethylenecarbamate linker exhibited the most powerful activity, which
      substantially exceeded that of the cholesterol homolog. Single-channel recording
      clearly exhibited that the ergosterol conjugate elicited channel current with the
      conductance of 28 pS, which was comparable with those by AmB, and revealed a
      higher channel open probability than the cholesterol conjugate. These results
      imply that direct interaction between amphotericin B and ergosterol is reproduced
      by their conjugate, which may serve as a model compound for understanding the
      drug's selective toxicity.

PMID- 15157879
TI  - Transforming a (beta/alpha)8--barrel enzyme into a split-protein sensor through
      directed evolution.
AB  - Split-protein sensors have become an important tool for the analysis of protein
      protein interactions in living cells. We present here a combinatorial method for
      the generation of new split-protein sensors and demonstrate its application
      toward the (beta/alpha)(8)-barrel enzyme N-(5'-phosphoribosyl)-anthranilate
      isomerase Trp1p from Saccharomyces cerevisiae. The generated split-Trp protein
      sensors allow for the detection of protein-protein interactions in the cytosol as
      well as the membrane by enabling trp1 cells to grow on medium lacking tryptophan.
      This powerful selection complements the repertoire of the currently used split
      protein sensors and provides a new tool for high-throughput interaction
      screening.

PMID- 15157880
TI  - Characterization of a conserved structural determinant controlling protein kinase
      sensitivity to selective inhibitors.
AB  - Some protein kinases are known to acquire resistance to selective small molecule
      inhibitors upon mutation of a conserved threonine at the ATP binding site to a
      larger residue. Here, we performed a comprehensive mutational analysis of this
      structural element and determined the cellular sensitivities of several disease
      relevant tyrosine kinases against various inhibitors. Mutant kinases possessing a
      larger side chain at the critical site showed resistance to most compounds
      tested, such as ZD1839, PP1, AG1296, STI571, and a pyrido[2,3-d]pyrimidine
      inhibitor. In contrast, indolinones affected both wild-type and mutant kinases
      with similar potencies. Resistant mutants were established for pharmacological
      analysis of betaPDGF receptor-mediated signaling and allowed the generation of a
      drug-inducible system of cellular Src kinase activity. Our data establish a
      conserved structural determinant of protein kinase sensitivity relevant for both
      signal transduction research and drug development.

PMID- 15157881
TI  - Identification of selective inhibitors for the glycosyltransferase MurG via high
      throughput screening.
AB  - Nucleotide-glycosyltransferases (NDP-Gtfs) play key roles in a wide range of
      biological processes. It is difficult to probe the roles of individual
      glycosyltransferases or their products because, with few exceptions, selective
      glycosyltransferase inhibitors do not exist. Here, we investigate a high
      throughput approach to identify glycosyltransferase inhibitors based on a
      fluorescent donor displacement assay. We have applied the screen to E. coli MurG,
      an enzyme that is both a potential antibiotic target and a paradigm for a large
      family of glycosyltransferases. We show that the compounds identified in the
      donor-displacement screen of MurG are selective for MurG over other enzymes that
      use similar or identical substrates, including structurally related enzymes. The
      donor displacement assay described here should be adaptable to many other NDP
      Gtfs and represents a new strategy to identify selective NDP-Gtf inhibitors.

PMID- 15157884
TI  - Protocols for experimentation with Schizosaccharomyces pombe.

PMID- 15157882
TI  - On the gene delivery efficacies of pH-sensitive cationic lipids via endosomal
      protonation: a chemical biology investigation.
AB  - In an effort to probe the importance of endosomal protonation in pH-sensitive,
      cationic, lipid-mediated, non-viral gene delivery, we have designed and
      synthesized a novel cholesterol-based, endosomal pH-sensitive, histidylated,
      cationic amphiphile (lipid 1), its less pH-sensitive counterpart with an electron
      deficient, tosylated histidine head group (lipid 2) as well as a third new
      cholesterol-based, cationic lipid containing no histidine head group (lipid 3).
      For all the novel liposomes and lipoplexes, we evaluated hysicochemical
      characteristics, including lipid:DNA interactions, global surface charge, and
      sizes. As anticipated, lipid 2 showed lower efficacies than lipid 1 for the
      transfection of 293T7 cells with the cytoplasmic gene expression vector pT7Luc at
      lipid:DNA mole ratios of 3.6:1 and 1.8:1; both lipids were greatly inhibited in
      the presence of Bafilomycin A1. This demonstrates the involvement of imidazole
      ring protonation in the endosomal escape of DNA. Conversely, endosome escape of
      DNA with lipid 3 seemed to be independent of endosome acidification. However,
      with nuclear gene expression systems in 293T7, HepG2, and HeLa cells, the
      transfection efficacies of lipid 2 at a lipid:DNA mole ratio of 3.6:1 were found
      to be either equal to or somewhat lower than those of lipids 1 and 3.
      Interestingly, at a lipid:DNA mole ratio of 1.8:1, lipids 2 and 3 were remarkably
      more transfection efficient than lipid 1 in both HepG2 and HeLa cells.
      Mechanistic implications of such contrasting relative transfection profiles are
      delineated.

PMID- 15157883
TI  - Synthetic glycoprotein mimics inhibit L-selectin-mediated rolling and promote L
      selectin shedding.
AB  - L-selectin is a leukocyte cell-surface protein that facilitates the rolling of
      leukocytes along the endothelium, a process that leads to leukocyte migration to
      a site of infection. Preventing L-selectin-mediated rolling minimizes leukocyte
      adhesion and extravasation; therefore, compounds that inhibit rolling may act as
      anti-inflammatory agents. To investigate the potential role of multivalent
      ligands as rolling inhibitors, compounds termed neoglycopolymers were synthesized
      that possess key structural features of physiological L-selectin ligands.
      Sulfated neoglycopolymers substituted with sialyl Lewis x derivatives (3',6
      disulfo Lewis x or 6-sulfo sialyl Lewis x) or a sulfatide analog (3,6-disulfo
      galactose) inhibited L-selectin-mediated rolling of lymphoid cells. Functional
      analysis of the inhibitory ligands indicates that they also induce proteolytic
      release of L-selectin. Thus, their inhibitory potency may arise from their
      ability to induce shedding. Our data indicate that screening for compounds that
      promote L-selectin release can identify ligands that inhibit rolling.

PMID- 15157885
TI  - Choosing and using Schizosaccharomyces pombe plasmids.
AB  - A wide range of plasmids has been developed for molecular studies in the fission
      yeast Schizosaccharomyces pombe. This includes general purpose episomes,
      expression vectors, epitope tagging plasmids, and integration vectors. This
      review describes the typical features of S. pombe vectors, including replication
      origins, positive and negative selection markers, and constitutive and inducible
      promoter systems. We will also discuss vectors with epitope tags and how these
      can be used to modify episomal or endogenous gene sequences. Considerations for
      choosing and using a plasmid are presented and specialized methods are described.

PMID- 15157887
TI  - The N-degron approach to create temperature-sensitive mutants in
      Schizosaccharomyces pombe.
AB  - Conditional mutants are a vital tool for analysis of gene function. The use of
      temperature-sensitive mutants in Schizosaccharomyces pombe has significantly
      promoted understanding of many cellular processes. A portable heat-inducible
      amino-terminal degron (N-degron) for conditional degradation of a gene product
      has been previously described in Saccharomyces cerevisiae. This paper describes
      the adaptation of the N-degron method to create temperature-sensitive (ts)
      mutants in S. pombe. A ts derivative of the mouse dihydrofolate reductase with an
      amino-terminal arginine (Arg-DHFR(ts)) previously described in S. cerevisiae was
      fused to the N-terminus of Bir1p, a nuclear protein involved in mitotic
      chromosome segregation in S. pombe. This fusion allele, referred to as bir1-td,
      conferred a chromosome segregation defect at 36 degrees C, as with previously
      described alleles of bir1. Deletion of the S. pombe E3 ubiquitin ligase (N
      recognin), Ubr11p, reversed the temperature-dependent lethality of bir1-td,
      providing evidence for N-end rule mediated destruction of Bir1p. The methods we
      describe should therefore facilitate analysis of essential genes in fission yeast
      for which conditionally lethal mutants are unavailable.

PMID- 15157886
TI  - Strategies for gene disruptions and plasmid constructions in fission yeast.
AB  - Molecular genetic analyses in Schizosaccharomyces pombe are greatly enhanced by
      our ability to delete chromosomal genes via homologous recombination and to
      introduce genes expressed from autonomous plasmids. In this paper, we describe a
      novel approach to generating marked deletion cassettes that bypasses the need for
      the long, PAGE-purified oligonucleotides required in the currently used PCR-based
      deletion approach. We also describe additional uses of this two-step PCR method
      for constructing chromosomal insertion cassettes. Finally, we describe how gap
      repair in S. pombe can facilitate plasmid constructions in a manner that
      circumvents the reliance on compatible restriction sites in the DNA molecules
      that are being joined. Several applications of this gap repair plasmid
      construction strategy are discussed.

PMID- 15157889
TI  - Imaging green fluorescent protein fusions in living fission yeast cells.
AB  - The use of green fluorescent protein (GFP) fusions as biosensors for examining
      protein localization and dynamics has revolutionized cell biology. Here, we
      describe the methods developed for imaging of GFP-fusions in the fission yeast
      Schizosaccharomyces pombe using fluorescence microscopy, with a focus on the use
      of time-lapse imaging to analyze the dynamics of microtubules. We discuss the
      considerations in fluorescence microscopy, cell preparation, data acquisition,
      and image analysis appropriate for analysis of living cells.

PMID- 15157888
TI  - In vivo labeling of fission yeast DNA with thymidine and thymidine analogs.
AB  - In vivo labeling of DNA with thymidine and thymidine analogs has long been a
      cornerstone of replication studies. Unfortunately, yeast lack a thymidine salvage
      pathway and thus do not incorporate exogenous thymidine. Specifically, yeast
      neither efficiently take up exogenous thymidine from their growth media nor
      phosphorylate it to thymidylate, the precursor of dTTP. We have overcome these
      problems in fission yeast by expressing the human equilibrative nucleoside
      transporter 1 (hENT1) along with herpes simplex virus thymidine kinase (tk).
      hENT1 tk cells are healthy and efficiently incorporate exogenous thymidine and
      thymidine analogs. We present protocols for labeling DNA with tritiated
      thymidine, for in situ detection of incorporated BrdU by immunofluorescence, for
      double labeling with CldU and IdU, for CsCl gradient separation of IdU-labeled
      DNA, and for using hENT1 and tk as both positive and negative selection markers.

PMID- 15157890
TI  - Nucleocytoplasmic transport and nuclear envelope integrity in the fission yeast
      Schizosaccharomyces pombe.
AB  - The nuclear envelope is essential for compartmentalizing the nucleus from the
      cytoplasm in all eukaryotic cells. There is a tremendous flux of both RNA and
      proteins across the nuclear envelope, which is intact throughout the entire cell
      cycle of yeasts but breaks down during mitosis of animal cells. Transport across
      the nuclear envelope requires the recognition of cargo molecules by receptors,
      docking at the nuclear pore, transit through the nuclear pore, and then
      dissociation of the cargo from the receptor. This process depends on the
      RanGTPase system, transport receptors, and the nuclear pore complex. We provide
      an overview of the nuclear transport process, with particular emphasis on the
      fission yeast Schizosaccharomyces pombe, including strategies for predicting and
      experimentally verifying the signals that determine the sub-cellular localization
      of a protein of interest. We also describe a variety of reagents and experimental
      strategies, including the use of mutants and chemical inhibitors, to study
      nuclear protein import, nuclear protein export, nucleocytoplasmic protein
      shuttling, and mRNA export in fission yeast. The RanGTPase and its regulators
      also play an essential transport independent role in nuclear envelope re-assembly
      after mitosis in animal cells and in the maintenance of nuclear envelope
      integrity at mitosis in S. pombe. Several experimental strategies and reagents
      for studying nuclear size, nuclear shape, the localization of nuclear pores, and
      the integrity of the nuclear envelope in living fission yeast cells are
      described.

PMID- 15157891
TI  - Tandem affinity purification and identification of protein complex components.
AB  - As with the budding yeast Saccharomyces cerevisiae, the completion of the
      Schizosaccharomyces pombe genome sequence has opened new opportunities to
      investigate the functional organization of a eukaryotic cell. These include
      analysis of gene expression patterns, comprehensive gene knockout and synthetic
      lethal screens, global protein localization analysis, and direct protein
      interaction mapping. We describe here the tandem affinity purification or TAP
      approach combined with DALPC mass spectrometry to identify components of protein
      complexes as we have applied it to S. pombe. This approach can theoretically be
      applied to the entire proteome as has been done in S. cerevisiae to gain insight
      into functional protein assemblies and to elucidate functions of uncharacterized
      proteins.

PMID- 15157892
TI  - Cell wall analysis.
AB  - The cell wall is a rigid structure essential for survival of the fungal cell.
      Because of its absence in mammalian cells, the cell wall is an attractive target
      for antifungal agents. Thus, for different reasons, it is important to know how
      the cell wall is synthesized and how different molecules regulate that synthesis.
      The Schizosaccharomyces pombe cell wall is mainly formed by glucose
      polysaccharides and some galactomannoproteins. Here, we describe a fast and
      reliable method to analyze changes in S. pombe cell wall composition by using
      specific enzymatic degradation and chemical treatment of purified cell walls.
      This approach provides a powerful means to analyze changes in (1,3)beta-glucan
      and (1,3)alpha-glucan, two main polysaccharides present in fungal cell walls.
      Analysis of cell wall polymers will be useful to search for new antifungal drugs
      that may inhibit cell wall biosynthesis and/or alter cell wall structure.

PMID- 15157894
TI  - Assaying the DNA damage checkpoint in fission yeast.
AB  - Cell cycle checkpoints exist to ensure the proper maintenance and stable
      inheritance of genomic information. The pathways that insure the faithful
      execution of these checkpoints are well conserved throughout evolution. In the
      fission yeast, Schizosaccharomyces pombe, a major cell cycle checkpoint exists
      that responds to the presence of damaged DNA and prevents this damage from being
      propagated to future generations. Fission yeast is an ideal system to investigate
      these pathways because there exist specific techniques that allow one to assay
      the fidelity of this DNA damage checkpoint pathway.

PMID- 15157893
TI  - Analysis of chromatin in fission yeast.
AB  - The use of fission yeast as a model system for studies of chromosome biology has
      contributed to several key advances in the last few years. The structure of its
      large complex centromeres and composition of its transcriptionally silent
      heterochromatin resemble those of metazoa. The application of chromatin
      immunoprecipitation to fission yeast has been instrumental in these advances and
      we describe an improved version of this technique in detail. In addition, we
      describe several other techniques, which are useful in the analysis of chromatin
      in fission yeast.

PMID- 15157896
TI  - Acute changes in dietary omega-3 fatty acid intake lowers soluble interleukin-6
      receptor in healthy adult normal weight and overweight males.
AB  - OBJECTIVE: To determine the effect of a short-term isocaloric exchange of alpha
      linolenic acid (ALA, 18:3n3) for linoleic acid (LA, 18:2n6) on fasting levels of
      soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-alpha
      receptors 1 and 2 (sTNFR1 and sTNFR2) in healthy normal weight and
      overweight/obese adult males. DESIGN: Four-day clinical intervention study with
      0.5% or 5% of total energy from ALA. Fasting (10 h) blood samples were obtained
      on the morning of day 5 in both diet treatments to measure sTNFR1, sTNFR2, and
      sIL6R. SUBJECTS: Nine normal weight (BMI < 25 kg/m2) and seven overweight (BMI >
      or = 25 kg/m2) healthy males. RESULTS: Fasting sIL6R decreased significantly from
      the control (C) diet following four days on the high ALA isocaloric (ISO) diet in
      normal weight and overweight/obese subjects (normal weight: C = 34.89 +/- 3.17
      ng/ml, ISO = 30.91 +/- 2.24 ng/ml, p < 0.05; overweight/obese: C = 38.19 +/- 3.92
      ng/ml, ISO = 33.57 +/- 2.47 ng/ml, p , 0.05). The dietary intervention did not
      have a significant effect on fasting sTNFR1 or sTNFR2. CONCLUSIONS: The results
      suggest that an isocaloric exchange of ALA for LA can reduce fasting sIL6R
      concentration by approximately 11% after a four-day dietary intervention in both
      overweight/obese and normal weight subjects. The data also suggest that longer
      exposure to a similar diet may have the potential to reduce inflammatory burden
      and thus lower the risk of both cardiovascular disease as well as diabetes.

PMID- 15157895
TI  - Inhibition of joint inflammation and destruction induced by anti-type II collagen
      antibody/lipopolysaccharide (LPS)-induced arthritis in mice due to deletion of
      macrophage migration inhibitory factor (MIF).
AB  - OBJECTIVE: Previous studies have demonstrated that neutralization of macrophage
      migration inhibitory factor (MIF) by anti-MIF antibody decreases joint
      destruction in the collagen-induced arthritis model. The present study was
      undertaken to investigate whether selective deletion of MIF inhibits inflammation
      and joint destruction of the anti-type II collagen antibody (anti-CII
      Ab)/lipopolysaccharide (LPS)-induced arthritis in mice, in order to determine the
      role of this cytokine in inflammatory arthritis. DESIGN: Anti-CII Ab/LPS-induced
      arthritis was induced in MIF-deficient and wild-type mice. The effects of anti
      MIF polyclonal antibody administration on anti-CII Ab-induced arthritis were also
      evaluated. RESULTS: The expression of MIF protein and mRNA was induced in anti
      CII Ab/LPS-induced arthritis joint tissues. Histopathological arthritis scores
      for synovial inflammation induced by anti-CII Ab/LPS -induced arthritis were
      significantly decreased in anti-MIF Ab-treated mice and in MIF-deficient mice
      compared to wild-type mice. In addition, mRNA levels of MMP-13 and MIP-2 in anti
      CII Ab/LPS-induced arthritis joint tissues were significantly reduced in MIF
      deficient mice compared to wild-type control mice. CONCLUSIONS: These results
      indicate that MIF plays a critical role in inflammation and joint destruction in
      the anti-CII Ab/LPS-induced arthritis model in mice, in part via induction of MMP
      13 and neutrophil infiltration through the induction of MIP-2.

PMID- 15157898
TI  - IgG-derived Fc down-regulates virus-induced plasmacytoid dendritic cell (pDC)
      IFNalpha production.
AB  - Interferon alpha (IFNalpha) produced primarily by plasmacytoid dendritic cells
      (pDC) is a potent component of the anti-viral innate immune response, and
      modulates adaptive immunity. Primary control of IFNalpha production occurs at a
      cellular level and is highly dependent upon regulatory factors and their
      products. Recent studies have identified up-regulation of IFNalpha production
      mediated by the adaptive immune response in the form of immune specific IgG.
      These studies establish a role for the external control of IFNalpha production.
      The current work demonstrates that the Fc portion of IgG is a potent inhibitor of
      IFNalpha produced by pDCs in response to HIV, HSV, and VSV. Fc down-regulation
      occurs after IFNalpha production can be detected by bioassay, and suggests the
      existence of late regulatory events in the control of IFNalpha production. Down
      regulation of IFNalpha is not caused by Fc-induced necrosis, apoptosis or
      neutralization of IFNalpha activity. Demonstration of Fc-mediated down-regulation
      of IFNalpha provides additional evidence of the role of IgG in the regulation of
      IFNalpha production.

PMID- 15157897
TI  - Differential regulation of cytokine and chemokine production in
      lipopolysaccharide-induced tolerance and priming.
AB  - LPS pretreatment of human pro-monocytic THP-1 cells induces tolerance to
      secondary LPS stimulation with reduced TNFalpha production. However, secondary
      stimulation with heat-killed Staphylococcus aureus (HKSa) induces priming as
      evidenced by augmented TNFalpha production. The pro-inflammatory cytokine,
      IFNgamma, also abolishes suppression of TNFalpha in LPS tolerance. The effect of
      LPS tolerance on HKSa and IFNgamma-induced inflammatory mediator production is
      not well defined. We hypothesized that LPS, HKSa and IFNgamma differentially
      regulate pro-inflammatory mediators and chemokine production in LPS-induced
      tolerance. THP-1 cells were pretreated for 24 h with LPS (100 ng/ml) or LPS (100
      ng/ml) + IFNgamma (1 microg/ml). Cells were subsequently stimulated with LPS or
      HKSa (10 microg/ml) for 24 h. The production of the cytokines TNFalpha, IL-6, IL
      1beta, and GMCSF and the chemokine IL-8 were measured in supernatants. LPS and
      HKSa stimulated TNFalpha (3070 +/- 711 pg/ml and 217 +/- 9 pg/ml, respectively)
      and IL-6 (237 +/- 8.9 pg/ml and 56.2 +/- 2.9 pg/ml, p < 0.05, n = 3,
      respectively) in control cells compared to basal levels (< 25 pg/ml). LPS induced
      tolerance to secondary LPS stimulation as evidenced by a 90% (p < 0.05, n = 3)
      reduction in TNFalpha. However, LPS pretreatment induced priming to HKSa as
      demonstrated by increased TNFalpha (2.7 fold, from 217 to 580 pg/ml, p < 0.05, n
      = 3 ). In contrast to suppressed TNFalpha, IL-6 production was augmented to
      secondary LPS stimulation (9 fold, from 237 to 2076 pg/ml, p < 0.01, n = 3) and
      also primed to HKSa stimulation (62 fold, from 56 to 3470 pg/ml, p < 0.01, n =
      3). LPS induced IL-8 production and to a lesser extent IL-1beta and GMCSF. LPS
      pretreatment did not affect secondary LPS stimulated IL-8 or IL-1beta, although
      HKSa stimulation augmented both mediators. In addition, IFNgamma pretreatment
      reversed LPS tolerance as evidenced by increased TNFalpha levels while IL-6, IL
      1beta, and GMCSF levels were further augmented. However, IL-8 production was not
      affected by IFNgamma. These data support our hypothesis of differential
      regulation of cytokines and chemokines in gram-negative- and gram-positive
      induced inflammatory events. Such changes may have implications in the
      pathogenesis of polymicrobial sepsis.

PMID- 15157899
TI  - Adipose tumor necrosis factor-alpha is reduced during onset of insulin resistance
      in Sprague-Dawley rats.
AB  - Overexpression of mRNA for tumor necrosis factor-alpha (TNF-alpha) has been
      observed in adipose tissue in several rodent models of insulin resistance. The
      purpose of the present study was to examine the expression of TNF-alpha protein
      during the onset of insulin resistance in maturing Sprague-Dawley (S-D) rats.
      Compared to 2 months, rats aged 5 and 12 months were glucose intolerant and
      fasting glucose was elevated at 12 months (p < 0.05). Compared to 2 months,
      insulin concentrations following glucose loading were elevated at 5 months (p <
      0.05) and also at 12 months, but to a lesser degree. In isolated strips of soleus
      muscle, insulin-stimulated glucose transport was reduced by 38% and 59% between 2
      and 5 months and between 2 and 12 months, respectively (p < 0.05), with no
      changes in basal transport. Insulin resistance was associated with decreased
      content of TNF-alpha protein in visceral and subcutaneous fat. TNF-alpha protein
      content was also decreased in tibialis anterior muscle, but was unchanged in
      soleus and red gastrocnemius muscles. Liver was the only tissue examined that
      showed an increase in TNF-alpha protein content. In vitro secretion of TNF-alpha
      protein was markedly reduced in explants of visceral and subcutaneous fat from
      mature, insulin-resistant animals, but TNF-alpha bioactivity in subcutaneous fat
      was maintained with age. These results indicate that the onset of insulin
      resistance in mature S-D rats is associated with reduced adipose expression of
      TNF-alpha. Our findings do not support the adipose-endocrine model of TNF-alpha
      in insulin resistance. Our findings do support a paracrine role for TNF-alpha or
      for a reduction in endogenous TNF-alpha inhibitors in insulin resistance.

PMID- 15157900
TI  - Are the immune responses different in middle-aged and young mice following bone
      fracture, tissue trauma and hemorrhage?
AB  - Although immune responses following soft-tissue trauma-hemorrhage are markedly
      different in young (6-8 weeks) and aged (18-20 months) mice, it remains unknown
      if there are any differences in immune responses in middle-aged and young mice
      following bone fracture, soft-tissue trauma-hemorrhage (Fx-TH). To study this,
      young (6-8 weeks) and middle-aged (approximately 12 months) C3H/HeN male mice
      were subjected to sham operation or Fx-TH followed by resuscitation with Ringer's
      lactate. The mice were sacrificed 2 h thereafter and splenocytes, bone marrow
      cells (BM) and Kupffer cells (KC) were harvested, purified and stimulated with
      ConA (for splenocytes) or LPS (for BM and KC) in vitro. Splenocyte release of Th1
      (IL-2 and IFN-gamma) cytokines was decreased and Th2 (IL-4 and IL-10) cytokine
      release was increased following Fx-TH in both young and middle-aged mice.
      However, the decrease in IL-2 and increase in IL-10 were significantly more in
      middle-aged mice compared to young mice (p < 0.05). Furthermore, splenocyte
      proliferation was decreased more in middle-aged mice compared to young mice
      following Fx-TH (p < 0.05). Additionally, TNF-alpha production was more in BM
      from middle-aged compared to BM from young mice after Fx-TH (p < 0.05). The
      production of IL-6 and IL-10 was also significantly higher in KC from middle-aged
      mice compared to young ones following Fx-TH. These results suggest that at middle
      age, the immune responses to Fx-TH are significantly different from those
      observed in young mice in different compartments of the body. Although the
      mechanism of the difference in various compartments in middle-aged vs. young mice
      following Fx-TH remains unknown, the decreased IL-2 production along with other
      altered T cell and macrophage functions may contribute to an increased
      susceptibility to sepsis in middle-aged vs. young individuals.

PMID- 15157901
TI  - Molecular complexes of IQ and 4-hydroxy-coumarin: a mutagen-anti-mutagen system.
AB  - Molecular complexes formed between a cooked food mutagen-carcinogen (2-amino-3
      methylimidazo[4,5-f] quinoline, IQ) and a potent anti-mutagen (4-hydroxy
      coumarin, 4HC) were synthesized and crystallized from a solution. The active
      functional groups in IQ and in 4HC that may involve in the formation of these
      complexes are investigated by UV-visible, infrared, and NMR spectroscopy. The
      geometrical conformations and heat of formation of IQ:4HC complexes were
      optimized by semi-empirical molecular orbital calculations. The experimental and
      theoretical results indicate that the complexes exist in multiple conformations.
      The energetically favorable ones are formed via hydrogen-bonding type of
      interactions between amino group in IQ and carbonyl group in 4HC, and also
      between quinoline-nitrogen (and imidazole-nitrogen) in IQ and hydroxyl group in
      4HC. The observed complex formation could serve as a model for understanding the
      active molecular sites responsible for the initial mutagenic activity in cooked
      food mutagens as well as the anti-mutagenic activity in coumarins.

PMID- 15157902
TI  - Biolocalisation and photochemical properties of two novel macrocyclic
      photosensitisers: a spectroscopic study.
AB  - Biolocalisation and photochemical properties of novel macrocyclic
      photosensitisers, guanidiniocarbonyl-substituted tetraphenylporphyrin (1) and
      sugar-substituted sapphyrin (2) were investigated by spectroscopic methods. Both
      photosensitisers absorb in far visible region and showed good tumour
      localisation. Photosensitiser 2 demonstrated significantly larger absolute and
      relative to normal tissue (T/N) amount in tumour (330 microg g(-1) wet tissue,
      T/N=19.0) than photosensitiser 1 did (13 microg g(-1) wet tissue, T/N=2.1).
      According to iodometric and uric acid assays, compound 1 produced large amount of
      1O2 (phidelta=0.60-0.68), while compound 2 showed non-significant 1O2 production
      (phidelta=0.04). The electronic spectroscopic study confirms that only
      photosensitiser 1 is able to mediate photooxidation of model compounds (BSA,
      poly(Trp), Tyr, Trp, and GMP) after light irradiation. Pour photochemical
      activity of compound 2 was explained by its self-aggregation. Raman spectroscopic
      study indicated that monomerised photosensitiser 2 effectively damaged BSA and
      calf thymus DNA after light excitation at the conditions of high excess of these
      macromolecules.

PMID- 15157903
TI  - Routine measurement of erythemally effective UV irradiance on inclined surfaces.
AB  - Measurements of erythemally weighted UV radiation are usually related to a
      horizontal surface. The radiation is weighted with the sensitivity of the human
      skin, but the surface of the human body has only few horizontal surfaces.
      Therefore the UV radiation on inclined surfaces has to be quantified to
      investigate UV effects on humans. To fulfill this task three fully automatic
      measuring systems were built to measure the erythemally weighted UV radiation in
      27 directions within 2 min. This system measures routinely during the whole day
      and has now been in operation for nearly three years (in total 2000 measurement
      days) under any kind of meteorological conditions. The measurements provide the
      informations needed for further investigations concerning the UV effects on
      humans. The calibration of the erythemally weighting radiometers was performed in
      a way to provide reliable UV index measurements for all directions. The results
      of four exemplary measurement days in summer and winter for clear sky and
      overcast conditions are presented.

PMID- 15157904
TI  - Intraspecific responses in grain quality of 10 wheat cultivars to enhanced UV-B
      radiation under field conditions.
AB  - Field studies were conducted to determine the potential for intraspecific
      responses in grain quality of 10 wheat (Triticum aestivum) cultivars to enhanced
      ultraviolet-B (UV-B, 280-315 nm) radiation. The plants were exposed to 5 kJm(-2)
      supplemental UV-B radiation, simulating a depletion of 20% stratospheric ozone.
      In wheat cultivars tested, intraspecific responses in 16 amino acid contents and
      total amino acid contents in grains were found. Out of tested wheat cultivars,
      Dali 905, Mianyang 20, Wenmai 3, Chuxiong 8807 and Huining 18 showed significant
      increase in proteins, and Yunmai 39 and Huining 18 showed significant increase
      while Dali 905 and Chuxiong 8807 showed significant decrease in total sugar,
      respectively. No wheat cultivar showed significant change in rough starch
      content. Out of 10 cultivars 9 had a positive quality response index (QRI), while
      only Yunmai 39 showed negative response (QRI -1.19). According to QRI, the
      tolerance of 10 wheat cultivars to UV-B radiation had the following sequence,
      Huining 18>Mianyang 20>Mianyang 26>Wenmai 3>Dali 905>Longchun 16>Fengmai
      24>Liaochun 9>Chuxiong 8807>Yunmai 39. Intraspecific responses in grain quality
      of 10 wheat cultivars to enhanced UV-B radiation existed under field conditions.

PMID- 15157906
TI  - Hair color changes and protein damage caused by ultraviolet radiation.
AB  - Ultraviolet and visible radiations are known to damage hair. However,
      quantitative data relating damage to hair type, proteins and color to the
      radiation wavelength are missing. We studied the effect of UV plus visible, UVA
      plus visible, visible mercury-vapor lamp radiation and sunlight on (blended)
      virgin dark-brown, blond and red hair and (one head) virgin black and curly dark
      brown hair. All hair types showed a substantial increase in protein loss in water
      after lamp and sun irradiation. The damaging effect of UVB was about 2-5 times
      higher than that of UVA plus visible radiation, depending on the hair type.
      Significant color changes were also observed in every hair type, after lamp and
      sun irradiation, being more pronounced for the light colored hairs. The
      luminosity difference parameter was the major contributor to the hair color
      changes, but significant changes in the red-green and yellow-blue parameters of
      every hair were observed. In this case, the damaging effect is ascribable mainly
      to UVA radiation. No significant changes in the mechanical properties or
      topography were observed in any case. We discuss these results in terms of hair
      type and composition and melanin types.

PMID- 15157905
TI  - Effects of different protocol doses of low power gallium-aluminum-arsenate (Ga-Al
      As) laser radiation (650 nm) on carrageenan induced rat paw ooedema.
AB  - The purpose of the present study was to investigate the effect of the low power
      laser therapy on the acute inflammatory process. Male Wistar rats were used. The
      rat paw oedema was induced by sub-plantar injection of carrageenan, the paw
      volume was measured before and 1, 2, 3 and 4 h after the injection using a
      hydroplethysmometer. To investigate the mechanism action of the Ga-Al-As laser on
      inflammatory oedema, parallel studies were performed using adrenallectomized rats
      or rats treated with sodium diclofenac. Different laser irradiation protocols
      were employed for specific energy densities (EDs), exposure times and repetition
      rates. The rats were irradiated with the Ga-Al-As laser during 80 s each hour.
      The ED that produced an anti-inflammatory effect were 1 and 2.5 J/cm(2), reducing
      the oedema by 27% (P<0.05) and 45.4% (P<0.01), respectively. The ED of 2.5
      J/cm(2) produced anti-inflammatory effects similar to those produced by the
      cyclooxigenase inhibitor sodium diclofenac at a dose of 1 mg/kg. In
      adrenalectomized animals, the laser irradiation failed to inhibit the oedema. Our
      results suggest that low power laser irradiation possibly exerts its anti
      inflammatory effects by stimulating the release of adrenal corticosteroid
      hormones.

PMID- 15157907
TI  - The binding properties of photosensitizer methylene blue to herring sperm DNA: a
      spectroscopic study.
AB  - Methylene blue (MB) is a phenothiazinium photosensitizer with promising
      applications in the photodynamic therapy (PDT) for anticancer treatment. The
      binding properties of MB to herring sperm DNA have been investigated by the
      measurements of absorption spectra, quenching experiments and the elucidation of
      the photobleaching processes. Remarkable hypochromic and bathochromic effects of
      MB in the presence of increasing amounts of DNA have been observed in the
      absorption spectra. The quenching of MB by the DNA bases obeys the Stern-Volmer
      equation and ferrocyanide quenching of MB in the absence and presence of DNA is
      also measured as extended experiments. Results from the above spectral
      measurements are all consistent with the intercalative binding mode of MB to DNA
      with the Kb value of 1.89 x 10(4) M(-1). The photobleaching processes of MB and
      its DNA complex have also been studies, which indicate that the photobleaching of
      MB and its DNA complex proceeds with different mechanisms and the reactive oxygen
      species are responsible for the self-sensitized photooxidation of MB.

PMID- 15157908
TI  - Investigation on DNA assembly to neutral red-cyclodextrin complex by molecular
      spectroscopy.
AB  - DNA assembling to neutral red (NR) and cyclodextrins (CDs)-NR inclusion complex
      has been investigated by means of absorption, fluorescence and resonance light
      scattering (RLS). Depending on the molar ratio R of NR:DNA, the binding of NR
      with DNA involved in two processes at pH 7.50 and ionic strength 0.0045. The
      first process occurs in R>2.5, where the neutral form of NR was predominant and
      enhanced RLS was observed, indicating the aggregation of NR neutral form
      molecules on the molecular surface of DNA. The second process occurs in R<2.5,
      where an absorption band at 540 nm and a fluorescent excitation and emission band
      at 550 and 607 nm respectively provided compelling evidence that the binding of
      NR to DNA leaded to extensive NR protonation even at pH 7.50, and that a
      protonated NR (the acidic form of NR) can form DNA adducts with a binding mode
      different from that of the unprotonated form (the neutral form of NR). The
      results were also illustrated by the CDs-NR supramolecular system. The
      experimental data showed that CDs including beta-CD, hydroxypropyl-beta-CD (HP
      beta-CD) and sulfobutylether-beta-CD (SBE-beta-CD) superior to include the
      neutral form of NR, in addition, the inclusion complex decomposed when it bound
      to DNA. Thus, the decomposed NR was also protonated to form DNA adducts with
      intercalative mode. In fact, CDs played a role to carry guest molecule to
      intercalate DNA. A related mechanism is proposed.

PMID- 15157909
TI  - Spectroscopic studies on electron transfer between plastocyanin and cytochrome
      b6f complex.
AB  - This paper reports the results of the research on the interaction between the
      highly active cytochrome b(6)f complex and plastocyanin, both isolated from the
      same source - spinachia oleracea plants. An equilibrium constant K between the
      cytochrome f of the cytochrome b(6)f complex and plastocyanin has been estimated
      by two independent spectroscopic techniques: steady-state absorption spectroscopy
      and stopped-flow. The second-order rate constants k2 for forward and backward
      electron transfer between cytochrome f and plastocyanin have been found between
      1.4-2 x 10(7) and 8-10 x 10(6) M(-1)s(-1), respectively, giving the value of an
      equilibrium constant of about 2+/-0.4 or a difference in redox potential between
      plastocyanin and cytochrome f of cytochrome b(6)f complex of ca. 17 mV. The value
      of K=1.7+/-0.3 has been estimated from steady-state experiments in which the
      initial and final concentrations of participating components after mixing have
      been estimated via differential spectra analysis or spectra deconvolution. We
      propose a method of evaluation of the final plastocyanin concentration after the
      electron transfer reaction between cytochrome bf complex and plastocyanin that
      overcomes the interference by the strong chlorophyll absorption in the spectral
      region where oxidised plastocyanin has its low extinction absorption band. The
      data from both experiments, in the system devoid of quinol being the electron
      donor to cytochrome b(6), suggest that in case of electron transfer from
      cytochrome f to plastocyanin electron transfer can either bypass cytochrome f or
      the Rieske iron-sulfur protein can be reduced prior to its movement to the quinol
      binding site of cytochrome b(6). The role of the Rieske protein in forward and
      backward electron transfer reactions is discussed.

PMID- 15157910
TI  - Estimation of leaf transmittance in the near infrared region through reflectance
      measurements.
AB  - A method, which allows one to compensate for the incomplete collection of
      transmitted light (T) by an integrating sphere, has recently been developed, and
      shown to be reliable provided that the absorptance (A) of the leaf in the NIR
      region (750-800 nm) can be neglected, allowing one to set R+T=1, where R denotes
      the reflectance; this implies that proper compensation can only be applied to
      healthy leaves, which do not absorb in the NIR region. To overcome this
      limitation, the feasibility of an alternative, requiring neither measurements of
      T nor an elaborate analysis of radiative transport through a leaf, is explored.
      Not surprisingly, this simplistic alternative provides results which (in general)
      do not agree with those found by using the compensation method, but the two
      approaches converge in the spectral regions where absorptance is low (that is,
      where R+T> or =0.9). The "T-through-R" method, as described here, thus provides
      an additional check on the correction factor used in conjunction with the
      integrating sphere, and extends the applicability of the compensation method to
      situations where NIR absorptance is not negligible, e.g., in the presence of
      'browning' pigments produced upon the oxidation of polyphenols during leaf
      senescence.

PMID- 15157911
TI  - Effect of binary and ternary polyethyleneglycol and/or beta-cyclodextrin
      complexes on the photochemical and photosensitizing properties of Naproxen.
AB  - The effect of the polyethylene glycol and/or beta-cyclodextrin on the
      photolability of aqueous solutions of the anti-inflammatory drug Naproxen was
      studied. In all systems studied, the photodegradation process followed zero-order
      kinetics, leading to the same photoproducts as in the absence of these additives.
      Kinetic studies revealed that the presence of polyethylene glycol (PEG) reduced
      drug photodegradation (phi=0.11 in water and phi=0.045 in the presence of 1% of
      PEG). By contrast, the binary inclusion complex, Naproxen:beta-CD, did not
      protect the drug from degradation, phi=0.11. However, the ternary complex,
      Naproxen:beta-CD:PEG, reduced the efficiency of the photodegradative process to a
      considerable extent, with phi=0.022 in this system. In all cases the presence of
      the different additives elicited a change in the photomixture composition, the
      alcoholic derivative being the major photoproduct formed. Nevertheless, the
      change in the efficiency of the process and the amount of the photoproducts
      formed in the different systems were not related with the biodamage produced by
      the drug. In this sense, the presence of free Naproxen clearly sensitized the
      photoperoxidation of linoleic acid. The photosensitizing effect decreased as the
      PEG concentration increased and was completely abolished by both the binary
      (Naproxen:beta-CD) and ternary (Naproxen:beta-CD:PEG) complexes. In light of
      these observations, it is possible to speculate that in these systems the
      prevention of biodamage would be due to a decrease in the contact between the
      short-lived species generated during Naproxen photodegradation and biological
      structures, rather than to the nature or amount of the photoproducts.

PMID- 15157912
TI  - Organogenesis and tissue engineering.

PMID- 15157913
TI  - Therapeutic cloning applications for organ transplantation.
AB  - A severe shortage of donor organs available for transplantation in the United
      States leaves patients suffering from diseased and injured organs with few
      treatment options. Scientists in the field of tissue engineering apply the
      principles of cell transplantation, material science, and engineering to
      construct biological substitutes that will restore and maintain normal function
      in diseased and injured tissues. Therapeutic cloning, where the nucleus from a
      donor cell is transferred into an enucleated oocyte in order to extract
      pluripotent embryonic stem cells, offers a potentially limitless source of cells
      for tissue engineering applications. The present chapter reviews recent advances
      that have occurred in therapeutic cloning and tissue engineering and describes
      applications of these new technologies that may offer novel therapies for
      patients with end-stage organ failure.

PMID- 15157914
TI  - Cell therapy using human embryonic stem cells.
AB  - Cell therapy refers to the transplantation of healthy, functional and propagating
      cells to restore the viability or function of deficient tissues. Stem cells are
      characterized by self-renewal and the potential to form differentiated cells. In
      early mammalian embryos, at the blastocyst stage, the inner cell mass is
      pluripotent. Thus, it has been recognized that human embryonic stem cells
      (hESCs), which are derived from such cells of blastocysts, may serve as a source
      of numerous types of differentiated cells. The first part of this review
      summarizes different techniques for the derivation and maintenance of
      undifferentiated hESCs. In the second part, issues concerning the safety and bulk
      production, which may enable hESCs use in future clinical applications, are
      presented. The last part of this review details accumulated data regarding the in
      vitro differentiation potential of hESCs.

PMID- 15157915
TI  - Treatment for end-stage renal disease: an organogenesis/tissue engineering
      odyssey.
AB  - The means by which kidney function can be replaced in humans with end-stage renal
      disease (ESRD) include dialytic therapies and renal allotransplantation.
      Dialysis, is lifesaving, but often poorly tolerated. Transplantation of human
      kidneys is limited by the availability of donor organs. During the past decades,
      several different approaches have been applied towards new means to replace renal
      function through organogenesis and tissue engineering. These include: (1)
      incorporation of new nephrons into the kidney; (2) growing new kidneys in situ;
      (3) use of stem cells; (4) generation of histocompatible tissues using nuclear
      transplantation; and (5) bioengineering of an artificial kidney. The development
      of these approaches has depended upon understanding and integrating discoveries
      made in a diversity of scientific disciplines. The means by which such
      integration has driven advances in the treatment of ESRD provides a generic
      roadmap for the successful application of organogenesis and tissue engineering to
      organ replacement therapy.

PMID- 15157916
TI  - Advances in cell therapy for renal failure.
AB  - Cell therapy is one of the most exciting fields in translational medicine. It
      stands at the intersection of a variety of rapidly developing scientific
      disciplines: stem cell biology, immunology, tissue engineering, molecular
      biology, biomaterials, transplantation biology, regenerative medicine and
      clinical research. Cell-based therapy may develop into a new therapeutic platform
      to treat a vast array of clinical disorders. Blood transfusions and bone marrow
      transplantation are prime examples of the successful application of cell-based
      therapeutics; but recent advances in cellular and molecular biology have expanded
      the potential applications of this approach. Although recombinant genetic
      engineering to produce a variety of therapeutics, such as human erythropoietin
      and insulin has proven successful, these treatments are unable to completely
      correct or reverse disease states, because most common disease processes are not
      due to the deficiency of a single protein but develop due to alterations in the
      complex interactions of a variety of cell components. In these complex
      situations, cell-based therapy may be a more successful strategy by providing a
      dynamic, interactive and individualized therapeutic approach that responds to the
      pathophysiological condition of the patient. In this regard, cells may provide
      innovative methods for drug delivery of biologics, immunotherapy, and tissue
      regenerative or replacement engineering [Nature 392 (1998) 518-524, Nat
      Biotechnol 20 (2002) 339-343]. The translation of this discipline to medicinal
      practice has tremendous potential, but in many applications technological issues
      need to be overcome. Since many cell-based indications are already being
      evaluated in the clinic, the field appears to be on the threshold of a number of
      successes. This review will focus on our group's use of human stem/progenitor
      cells in the treatment of acute and chronic renal failure as extensions to
      current successful renal substitution processes of hemodialysis and
      hemofiltration.

PMID- 15157917
TI  - Organogenesis of kidneys following transplantation of renal progenitor cells.
AB  - One novel solution to the shortage of human organs available for transplantation
      envisions 'growing' new organs in situ via xenotransplantation of developing
      anlagen from animal embryos. We and others have shown that renal progenitor cells
      (metanephroi) transplanted into animal hosts undergo organogenesis
      (differentiation and growth), become vascularized by blood vessels of host origin
      and exhibit excretory function. Metanephroi can be stored for up to 3 days in
      vitro prior to transplantation with no impairment in growth or function post
      implantation. Metanephroi can be transplanted across both concordant (rat to
      mouse) and highly disparate (pig to rodent) xenogeneic barriers. Here we review
      studies exploring the potential therapeutic use of embryonic kidney
      transplantation as a means to achieve renal organogenesis.

PMID- 15157918
TI  - Engraftment of human early kidney precursors.
AB  - Kidney transplantation has been one of the major medical advances of the past 30
      years; however, it is becoming increasingly apparent that the supply of organs is
      limited and will not improve with current medical practice. This review
      summarizes recent data whereby precursors of the adult kidney found in embryos
      and fetal tissue have been grafted into murine hosts to examine their feasibility
      as an alternative source for renal transplantation. When obtained at specific
      time points during human gestation, kidney precursors meet with specific demands;
      they grow tremendously, differentiate exclusively along the nephric lineage with
      no evidence of malignant transformation, become vascularised, to a larger extent,
      by host vessels, and produce urine in host animals. In addition, they exhibit
      decreased immunogenicity compared to adult counterparts. Organogenesis is best
      achieved when utilizing early undifferentiated progenitors rather than later
      gestation kidneys. Nevertheless, in order for these transplants to be applicable
      for human transplantation, both a functional urinary anastomosis and derivation
      of blood supply sufficient to correct biochemical abnormalities remain to be
      established.

PMID- 15157919
TI  - Organogenesis of endocrine pancreas from transplanted embryonic anlagen.
AB  - The number of donor human pancreas organs that can be transplanted directly or
      used for islet of Langerhans isolation is limited. We and others have shown that
      it is possible to 'grow' new pancreatic tissue in situ by transplanting embryonic
      organ-specific pancreatic precursor cells. This technology takes advantage of the
      fact that selective development of islets takes place post transplantation of
      embryonic pancreas and that the developing organ can attract its blood supply
      from an appropriate vascular bed post transplantation, enabling the
      transplantation of pancreas in 'cellular' form. Whole pancreatic anlagen
      implanted into a host peritoneum develop into a novel organ consisting of
      functional islets of Langerhans surrounded by stroma or individual alpha and beta
      cells within omental fat. Transplantation of developing pancreas to achieve
      organogenesis of its endocrine components could lead to a novel treatment for
      diabetes mellitus.

PMID- 15157921
TI  - Cellular therapies for liver replacement.
AB  - Insufficient donor organs for orthotopic liver transplantation worldwide have
      urgently increased the requirement for new therapies for acute and chronic liver
      disease. Whilst none are yet clinically proven there are at least two different
      approaches for which there is extensive experimental data, some human anecdotal
      evidence and some data emerging from Phase 1 clinical trials. Both approaches
      involve bio-engineering. In vivo tissue engineering involves isolated liver cell
      transplantation into the liver and/or other ectopic sites and in vitro tissue
      engineering, using an extracorporeal hepatic support system or bioartificial
      liver. Some questions are common to both these approaches, such as the best cell
      source and the therapeutic mass required, and are discussed. Others are specific
      to each approach. For cell transplantation in vivo the initial engraftment and
      repopulation will make a critical difference to the outcome, and development of
      markers for transplanted cells has enabled significant advances in understanding,
      and therefore manipulating, the process. Moreover, the role of immunosuppression
      is also important and novel approaches to natural immunosuppression are
      discussed. For use in a bioartificial liver, the ability for hepatocytes to
      perform ex vivo at in vivo levels is critical. Three dimensional culture improves
      cell performance over monolayer cultures. Alginate encapsulated cells offer a
      suitable 3-D environment for a bioartificial liver since they are both easily
      manipulatable and cryopreservable. The use of cells derived from stem cells or
      foetal rather than adult liver cells is also emerging as a potential human cell
      source which may overcome problems associated with xenogeneic cells.

PMID- 15157920
TI  - In vitro-generation of surrogate islets from adult stem cells.
AB  - Type 1 diabetes is one of the more costly chronic diseases of children and
      adolescents throughout North America and Europe, exhibiting an average estimated
      prevalence rate of nearly 0.2%. It occurs in genetically predisposed individuals
      when the immune system attacks and destroys specifically the insulin-producing
      beta cells of the pancreatic islets of Langerhans. While routine insulin therapy
      can provide diabetic patients with their daily insulin requirements, non
      compliance and undetected hyperglycemic excursions often lead to subsequent long
      term microvascular and macrovascular complications. The only real cure for type 1
      diabetes is replacement of the beta cell mass, currently being accomplished
      through ecto-pancreatic transplantation and islet implantation. Both of these
      procedures suffer from a chronic shortage of available donor tissue in comparison
      to the number of potential recipients. To circumvent this need, three alternative
      approaches are being intensively investigated: (1) the production of surrogate
      cells by genetically modifying non-endocrine cells to secrete insulin in response
      to glucose challenge; (2) the trans-differentiation of non-endocrine
      stem/progenitor cells or mature cells to glucose-responsive adult tissue; and (3)
      the regulated differentiation of islet stem/progenitor cells to produce large
      numbers of mature, functional islets. In recent years, each of these approaches
      has made impressive advances, leading to the most important question, 'how soon
      will this new science be available to the patient?' In the present review, we
      discuss some of the recent advances, focusing primarily on the differentiation of
      islet stem cells to functional endocrine pancreas that may form the basis for
      future treatment.

PMID- 15157922
TI  - Emerging insights into liver-directed cell therapy for genetic and acquired
      disorders.
AB  - Treatment of acute or chronic liver diseases by cell transplantation is an
      attractive prospect because organ shortages greatly restrict liver
      transplantation. Moreover, a variety of genetic deficiency states affecting
      extrahepatic organs are amenable to liver-directed cell therapy. While the
      initial clinical experience with liver cell transplantation has been encouraging,
      further advances in several areas are necessary to improve these results.
      Insights into how engraftment and proliferation of transplanted cells may be
      modulated to obtain therapeutically effective masses of transplanted cells will
      be important in this pursuit. Studies of cell therapy in animal models of
      specific diseases have provided insights into the development of clinically
      relevant strategies for various disorders. Also, identification of suitable cell
      types, including stem/progenitor cells that could be expanded and manipulated in
      cell culture conditions, has begun to provide important new information for cell
      therapy. Similarly, advances in cryopreservation of cells and prevention of
      allograft rejection offer ways to accomplish cell therapy in an effective manner.
      Taken together, these advances indicate that liver-directed cell therapy will be
      well positioned in the near future to play significant roles in transplantation
      medicine.

PMID- 15157923
TI  - Hepatic tissue engineering.
AB  - Fulminant hepatic failure (FHF) attributes to rising medical cost and accounts
      for many deaths each year in the United States. Currently, the only solution is
      organ transplantation. Due to increasing donor organ shortage, many in need of
      transplantation continue to remain on the waiting list. Liver Assist Devices
      (LADs) are being used to temporarily sustain liver function and bridge the period
      between FHF and transplantation. Hepatic Tissue Engineering is a step toward
      alleviating the need for donor organs; yet many challenges must be overcome
      including scaffold choice, cell source and immunological barriers. Bioreactors
      have aided in hepatocyte survival and have proven to sustain viable cells for
      several weeks. Achieving the necessary functions required for hepatic replacement
      is aided by the incorporation of growth factors and mitogens many that now can be
      bound to the polymer scaffold and released in a timely manner. Utilizing concepts
      such as MicroElectroMechanical systems (MEMs) technology, our laboratory is able
      to mimic the natural vasculature of the liver and sustain functional and viable
      hepatocytes. Expanding and improving upon this platform technology, advancements
      made will continue toward the development of a fully functioning and implantable
      liver.

PMID- 15157924
TI  - Muscle-derived stem cells for musculoskeletal tissue regeneration and repair.
AB  - Muscle recently has been identified as a good source of adult stem cells that can
      differentiate into cells of different lineages. The most well-known muscle
      progenitor cells are satellite cells, which not only contribute to the
      replenishment of the myogenic cell pool but also can become osteoblasts,
      adipocytes and chondrocytes. Other populations of stem cells that appear to be
      distinct from satellite cells also have been discovered recently. Muscle-derived
      stem cells (MDSCs) can be divided into two major categories based on these cells'
      varied abilities to differentiate into myogenic lineages. Interestingly, MDSCs
      that can differentiate readily into myogenic cells are usually CD45-. In
      contrast, MDSCs with less myogenic potential are CD45+. Various lines of evidence
      suggest that different populations of MDSCs are closely related. Furthermore,
      MDSCs appear to be closely related to endothelial cells or pericytes of the
      capillaries surrounding myofibers. When used in tissue engineering applications,
      MDSCs--particularly those genetically engineered to express growth factors--have
      been demonstrated to possess great potential for the regeneration and repair of
      muscle, bone and cartilage. Further research is necessary to delineate the
      relationship between different populations of MDSCs and between MDSCs and other
      adult stem cells, to investigate their developmental origin, and to determine the
      regulatory pathways and factors that control stem cell self-renewal,
      proliferation and differentiation. This knowledge could greatly enhance the
      usefulness of muscle-derived stem cells, as well as other adult stem cells, for
      tissue repair and regeneration applications.

PMID- 15157925
TI  - The cellular repair of the brain in Parkinson's disease--past, present and
      future.
AB  - Damage to the central nervous system was once considered irreparable. However,
      there is now growing optimism that neural transplant therapies may one day enable
      complete circuit reconstruction and thus functional benefit for patients with
      neurodegenerative conditions such as Parkinson's disease (PD), and perhaps even
      those with more widespread damage such as stroke patients. Indeed, since the late
      1980s hundreds of patients with Parkinson's disease have received allografts of
      dopamine-rich embryonic human neural tissue. The grafted tissue has been shown to
      survive and ameliorate many of the symptoms of the disease, both in the clinical
      setting and in animal models of the disease. However, practical problems
      associated with tissue procurement and storage, and ethical concerns over using
      aborted human fetal tissue have fuelled a search for alternative sources of
      suitable material for grafting. In particular, stem cells and xenogeneic
      embryonic dopamine-rich neural tissue are being explored, both of which bring
      their own practical and ethical dilemmas. Here we review the progress made in
      neural transplantation, both in the laboratory and in the clinic with particular
      attention to the development of stem cell and xenogeneic tissue based therapy.

PMID- 15157926
TI  - Stem cell transplantation and other novel techniques for promoting recovery from
      spinal cord injury.
AB  - A number of potential approaches aim to optimize functional recovery after spinal
      cord injury. They include minimizing the progression of secondary injury,
      manipulating the neuroinhibitory environment of the spinal cord, replacing lost
      tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded
      axons, and maximizing the intrinsic regenerative potential of endogenous
      progenitor cells. We review the application of stem cell transplantation to the
      spinal cord, emphasizing the use of embryonic stem cells for remyelinating
      damaged axons. We speculate that harnessing the potential of endogenously born
      stem cells already present in the spinal cord represents an important therapeutic
      target. We also discuss the potential application of peripheral nervous system
      reconstruction to recovery from spinal cord injury. The principles of peripheral
      nerve regeneration and concepts of nerve grafting are reviewed. Particular
      attention is given to peripheral nerve allotransplantation for repairing
      extensively injured tissue when autologous donor nerve material is scarce. The
      potential role of nerve transfers for reconstructing the injured spinal cord,
      particularly the cauda equina and lumbosacral plexus, are also described.

PMID- 15157927
TI  - Heart valve tissue engineering.
AB  - Valvular heart disease is a significant cause of morbidity and mortality world
      wide. Classical replacement surgery involves the implantation of mechanical
      valves or biological valves (xeno- or homografts). Tissue engineering of heart
      valves represents a new experimental concept to improve current modes of therapy
      in valvular heart surgery. Various approaches have been developed differing
      either in the choice of scaffold (synthetic biodegradable polymers,
      decellularised xeno- or homografts) or cell source for the production of living
      tissue (vascular derived cells, bone marrow cells or progenitor cells from the
      peripheral blood). The use of autologous bone marrow cells in combination with
      synthetic biodegradable scaffolds bears advantages over other tissue engineering
      approaches: it is safe, it leads to complete autologous prostheses and the cells
      are more easily obtained in the clinical routine. Even though we demonstrated the
      feasibility to construct living functional tissue engineered heart valves from
      human bone marrow cells, so far their general potential to differentiate into non
      hematopoietic cell lineages is not fully exploited for tissue engineering
      applications.

PMID- 15157928
TI  - Xenogeneic extracellular matrix as a scaffold for tissue reconstruction.
AB  - Bioscaffolds derived from xenogeneic extracellular matrix (ECM) have been used in
      numerous tissue engineering applications. The safety and efficacy of such
      scaffolds when used for the repair and reconstruction of numerous body tissues
      including musculoskeletal, cardiovascular, urogenital and integumentary
      structures has been shown in both preclinical animal studies and in human
      clinical studies. More than 200,000 human patients have been implanted with
      xenogeneic ECM scaffolds. These ECM scaffolds are typically prepared from porcine
      organs such as small intestine or urinary bladder, which are subjected to
      decellularization and terminal sterilization without significant loss of the
      biologic effects of the ECM. The composition of these bioscaffolds includes the
      structural and functional proteins that are part of native mammalian
      extracellular matrix. The three-dimensional organization of these molecules
      distinguishes ECM scaffolds from synthetic scaffold materials and is associated
      with constructive tissue remodeling instead of scar tissue. The biologic response
      to these xenogeneic bioscaffolds, including the immune response, is discussed
      herein.

PMID- 15157929
TI  - From A&E to ICU: how nurses can support the Surviving Sepsis Campaign.

PMID- 15157930
TI  - The role and accountability of senior health care support workers in intensive
      care units.
AB  - BACKGROUND: Nurses have always looked to support their activities through the
      presence of unregistered co-workers. In the later part of the 20th century this
      workforce has evolved from a predominance of students to increasing use of
      variously prepared second level nurses, nursing assistants and Health Care
      Support Workers. METHOD: The study evaluated the development of 'advanced'
      support workers for intensive care settings, examining the views of the multi
      disciplinary team, the support workers, and making observations of the work
      undertaken. Ethical approval was gained via a multi-centre committee. Individual
      interviews, focus groups and fieldwork provided rich qualitative data. It is
      this, and the views of support workers themselves on which we focus in this
      report. RESULTS: Senior support workers have a potentially important, but as yet
      insufficiently clear role to play. Key tasks such as taking arterial blood gas
      symbolise their rite of passage into the role. Expectations vary by locality and
      by person and there is great concern over accountability for work done.
      Delegation of work depends as much on experience as training and individuals are
      reluctant to delegate to staff they have not personally assessed and come to know
      as 'competent'. CONCLUSION: These workers should have clear and adequately
      remunerated career pathways open to them, in particular into nursing and allied
      health disciplines, and should probably be licensed to practice.

PMID- 15157931
TI  - Bridging the gap between the intensive care unit and general wards-the ICU
      Liaison Nurse.
AB  - The acute care system in our public hospitals has seen an increase in acuity for
      multiday patients with associated pressure on access to the intensive care unit
      (ICU) beds for both elective and emergency patients. When an ICU bed has not been
      available at this hospital, it has resulted in elective surgery being cancelled
      and/or emergency patients requiring an ICU admission being transferred to other
      hospitals. Apart from the problems either of these situations can cause to
      patients and their families, both government and hospital managements expect that
      access to an ICU (or other) bed will be available for patients in our community
      who require this level of care. To maximise access to our ICU beds it was
      necessary to ensure that length of stay (LOS) in ICU was kept to the minimum
      required for each individual patient and that re-admission rates to ICU for
      preventable complications were reduced. This paper relates our experience of
      developing and introducing an advanced practice nursing position (the ICU Liaison
      Nurse) in 1998, to oversee the transition of patients discharged from ICU to the
      general wards. Between 1997 and 2002 with the development of the ICU Liaison
      Nurse (ICU LN) post, medical readmissions to ICU were reduced from 2.3 to 0.5%.
      It is now 5 years since the position was introduced and the role has evolved over
      this time so that today the ICU LN not only bridges the gap between ICU and ward
      based care, but when necessary can be involved in the care of patients on the
      ward whose condition has deteriorated to the point where transfer into ICU may be
      necessary.

PMID- 15157932
TI  - Which nursing issues need a European guideline: proposal for respiratory
      management.
AB  - Over the past 30 years, nursing care and health systems have undergone
      significant changes in many aspects. Particularly, in the last decade, research
      and the expansion of Evidence-Based Practice (EBP) have played a significant role
      in this process. EBP is the application of the best available evidence, which in
      practice means more effective interventions, more efficient use of resources and
      fewer side effects for patients. From a research point of view, EBP can
      facilitate the identification of knowledge gaps and thereby help establish
      research priorities. Furthermore, research evidence may suggest that a change in
      practice is necessary. When this occurs, one of the best ways to implement such
      change is through the use of guidelines. Clinical Practice Guidelines (CPG) are
      "systematically developed statements to assist practitioner decisions about
      appropriate healthcare for specific clinical circumstances". Whenever possible,
      CPG help to infuse research into practice and to promote quality and
      standardisation of care. Nursing care will have a considerably greater impact if
      evidence-based care is applied. For this reason, it is important to identify the
      available evidence of respiratory management in order to establish nursing CPG
      across Europe. The aim of this paper is to analyse the framework in which these
      guidelines should be applied and to identify which nursing issues should have
      CPG. Based on the North American Nursing Diagnosis Association (NANDA), Nursing
      Interventions Classification (NIC) and the Nursing Outcomes Classification (NOC),
      this study establishes the main nursing diagnoses for a patient with Acute
      Respiratory Failure (ARF). Moreover, the current situation regarding respiratory
      management and the safety of nursing practice procedures are described.

PMID- 15157933
TI  - Practical considerations in the administration of intravenous vasoactive drugs in
      the critical care setting: the double pumping or piggyback technique-part one.
AB  - Part I of this review aims to identify the factors associated with safe
      administration of continuous intravenous vasoactive drug therapy, specifically
      epinephrine and norepinephrine. Intravenous vasoactive drugs are administered in
      the critical care setting to maintain patients' cardiovascular function by
      continuous intravenous infusion. To ensure uninterrupted administration, one
      infusion is commenced when the other is almost empty. A technique often employed
      to achieve this is known as 'double pumping' or 'piggybacking'. Due to the
      absence of a standardised protocol for administering continuous intravenous
      vasoactive medication and technological developments in infusion pumps, a review
      of current literature was undertaken. Despite a paucity of evidence regarding
      safe administration of these drugs, recommendations from the available literature
      included ensuring that critical care nurses are competent and formally trained in
      the use of equipment and the administration of continuous intravenous vasoactive
      medication. Furthermore, the infusion pump should feature minimal start up delay,
      a sensitive occlusion alarm system and the absence of a bolus in the event of
      infusion occlusion. This may reduce patients experiencing adverse haemodynamic
      responses due to alterations to the infusion. Indeed, a review of the 'double
      pumping' or 'piggybacking' technique in the clinical setting is required to
      establish current practice and develop evidence based guidelines.

PMID- 15157934
TI  - Subarachnoid haemorrhage and vasospasm: using physiological theory to generate
      nursing interventions.
AB  - Caring for critically ill patients with a subarachnoid haemorrhage and preventing
      its most prevalent and devastating complication, vasospasm, requires an in-depth
      understanding of the mechanisms which underpin the physiology of SAH. This is
      essential to provide appropriate nursing practice derived from theory. All too
      often practitioners are asked to follow unsubstantiated regimes without question
      of the origins of practices. This paper approaches the physiological theory
      underpinning the mechanisms surrounding subarachnoid haemorrhage and the altered
      cerebral and extracerebral dysfunction which can occur. Physiological theory is
      analysed to generate nursing interventions which may be individually tailored to
      provide comprehensive nursing care with a sound underpinning to its practice. The
      foundations of effective management of SAH lies within prevention, early
      diagnosis, and correction of complications [Neurosurg. Clin. North Am. 9 (3)
      (1998) 595]. In order for such identification to take place, it is essential to
      have an understanding of the physiological theory that underpins the basis of
      care interventions. These interventions should compliment all other theoretical
      input that influences patient care and nursing practice, contributing to a
      holistic, dynamically formulated plan of care.

PMID- 15157935
TI  - It happened to an ICU nurse : an experience on the receiving end of intensive
      care.
AB  - After working in intensive care for thirteen years, I believed I understood some
      of the experiences of our patients and their families. However, my own experience
      on the receiving end of intensive care has demonstrated how little I knew and has
      changed not only my own views and perceptions, but has stimulated changes to
      practice in one icu.

PMID- 15157936
TI  - Maintaining copper homeostasis: regulation of copper-trafficking proteins in
      response to copper deficiency or overload.
AB  - Copper is an essential micronutrient that plays a vital role as a catalytic co
      factor for a variety of metalloenzymes. The redox chemistry of copper also makes
      it a potentially toxic metal if not properly used. Therefore, elaborate
      mechanisms have evolved for controlling its cellular uptake, elimination, and
      distribution. In the last decade, our understanding of the systems involved in
      maintaining copper homeostasis has improved considerably with the
      characterization of copper transporters that mediate cellular copper uptake or
      efflux and with the identification of copper chaperones, a family of proteins
      required for delivering copper to specific targets in the cell. Despite the
      distinct roles of these proteins in copper trafficking, all seem able to respond
      to changes in copper status. Here, we describe recent advances in our knowledge
      of how copper-trafficking proteins respond to copper deficiency or overload in
      mammalian cells in order to maintain copper balance.

PMID- 15157937
TI  - Effect on rat arterial blood pressure of chemically generated peroxyl radicals
      and protection by antioxidants.
AB  - Convincing evidence suggests that blood redox changes play a role in the
      development of various cardiovascular disorders including hypertension.
      Nutritional antioxidants have been suggested to play a role in cardiovascular
      disease prevention. In this study, we investigated in vivo changes in rat
      arterial blood pressure induced by acute exposition to an increased load of
      peroxyl radicals and by the administration of selected antioxidants after
      chemically induced oxidative stress. Hydrosoluble and liposoluble peroxyl
      radicals, generated by 2,2'-azobis-(2-amidinopropane) dihydrochloride and 2,2'
      azobis 2,4-di-methylvaleronitrile, induced a dose-dependent decrease in rat blood
      pressure. All antioxidants tested (6-hydroxy-2,5,7,8-tetramethylchroman-2
      carboxylic acid, vitamin C, glutathione and dithiothreitol) returned peroxyl
      radical-induced hypotension to normal. Of the various antioxidants tested,
      glutathione was the most effective in restoring blood pressure after peroxyl
      radical generation. Treatment of rats with a thiol-chelating agent (N
      ethylmaleimide) and an oxidizing agent (5,5'-dithiobis-2-nitrobenzoic) inhibited
      peroxyl radical-mediated hypotension. Our results suggest that acute exposition
      to peroxyl radicals have a hypotensive effect on blood pressure and that thiols
      play an active role in the redox regulation of blood pressure. Other experiments
      are needed to clarify the role played by oxidative potentials on blood pressure
      and the mechanism of action of nutritional antioxidants.

PMID- 15157938
TI  - Physiologic estradiol levels enhance hypothalamic expression of the long form of
      the leptin receptor in intact rats.
AB  - Estradiol is a potent hypophagic agent that reduces food intake and body weight
      without a concomitant fall in plasma leptin levels. We investigated whether the
      hypophagic effect of estradiol is mediated by stimulating POMC and/or inhibiting
      NPY neuronal pathways in the hypothalamus, which respectively inhibit and
      stimulate feeding. We examined hypothalamic gene expression of Ob-Rb, NPY, POMC,
      MC4-R, and AgRP in intact Wistar rats treated with estradiol for 48 hours. Food
      intake and body weight were reduced in estradiol-treated rats but fat mass was
      unchanged; plasma leptin and insulin levels were not significantly different from
      untreated, freely fed controls. In untreated rats that were pair-fed to match the
      estradiol-treated group, body weight was also reduced without changes in fat
      mass, although leptin and insulin levels decreased significantly. Ob-Rb
      expression was increased in both hypophagic groups despite serum leptin were only
      decreased in pair-fed animals, suggesting an estradiol-stimulating effect on Ob
      Rb expression. No significant differences were found in POMC, AgRP, or MC4-R
      expression among any of the experimental groups. A significant but small decrease
      in NPY expression was also found in both hypophagic groups; this was explained by
      the combined effect of both surgery and reduced food intake. These results
      indicate that estradiol mediated hypophagia in intact rats could be brought about
      by an enhanced hypothalamic leptin sensitivity but is unlikely to be driven by
      changes in NPY or melanocortin system.

PMID- 15157939
TI  - Globus pallidus: a target brain region for divalent metal accumulation associated
      with dietary iron deficiency.
AB  - Recently, iron deficiency has been connected with a heterogeneous accumulation of
      manganese in the rat brain. The striatum is particularly vulnerable, for there is
      a significant negative correlation between accumulated manganese and gamma
      aminobutyric acid levels. The effect of dietary iron deficiency on the
      distribution of zinc and copper, two other divalent metals with essential
      neurobiological roles, is relatively unexplored. Thus, the primary goal of this
      study was to examine the effect of manipulating dietary iron and manganese levels
      on the concentrations of copper, iron, manganese and zinc in five rat brain
      regions as determined with inductively coupled plasma mass spectrometry analysis.
      Because divalent metal transporter has been implicated as a transporter of brain
      iron, manganese, and to a lesser extent zinc and copper, another goal of the
      study was to measure brain regional changes in transporter levels using Western
      blot analysis. As expected, there was a significant effect of iron deficiency (P
      < 0.05) on decreasing iron concentrations in the cerebellum and caudate putamen;
      and increasing manganese concentrations in caudate putamen, globus pallidus and
      substantia nigra. Furthermore, there was a significant effect of iron deficiency
      (P < 0.05) on increasing zinc concentration and a statistical trend (P = 0.08)
      toward iron deficiency-induced copper accumulation in the globus pallidus.
      Transporter protein in all five regions increased due to iron deficiency compared
      to control levels (P < 0.05); however, the globus pallidus and substantia nigra
      revealed the greatest increase. Therefore, the globus pallidus appears to be a
      target for divalent metal accumulation that is associated with dietary iron
      deficiency, potentially caused by increased transporter protein levels.

PMID- 15157940
TI  - Caffeine suppresses the expression of the Bcl-2 mRNA in BeWo cell culture and rat
      placenta.
AB  - Chronic caffeine exposure during pregnancy has an effect on fetal growth;
      however, the adverse effects of caffeine on embryogenesis are not well understood
      and controversial. We used cDNA microarray technology to determine whether
      caffeine alters gene expressions in a human cytotrophoblast-like cell line, BeWo.
      We found that the expression of the B-cell CLL/lymphoma 2 (Bcl-2) gene in BeWo
      cells was down-regulated by caffeine, suggesting that chronic exposure during the
      gestational period could exert an influence on embryogenesis. We then focused on
      the Bcl-2- and Bcl-2-associated X protein gene, Bax, to study the responsive gene
      expression in BeWo cells as well as placentas of pregnant rats fed a diet
      supplemented with caffeine (2 mg/100 g body weight) during gestation, and
      analyzed the gene expressions using LightCycler-based quantitative real-time
      polymerase chain reaction assays. We found a significantly decreased level of Bcl
      2 mRNA expression, which demonstrated the influence of caffeine on placental
      function.

PMID- 15157941
TI  - Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor
      alpha in rats with sucrose-induced metabolic syndrome.
AB  - Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing
      abnormalities associated with the metabolic syndrome and mortality from coronary
      heart disease. We investigated the effects of dietary fish oil on the metabolic
      syndrome in a high-sucrose-fed rat model. The model was achieved by the
      administration of 30% sucrose in drinking water in male Wistar rats during 21
      weeks. After the metabolic syndrome rat model was established, fish oil was
      administered during 6 weeks. The metabolic syndrome rats showed significant
      increases in body weight, systolic blood pressure, serum insulin, total lipids,
      triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin,
      and serum tumor necrosis factor-alpha (TNF-alpha). They also presented abdominal
      and epididymal fat accumulation and fatty liver. After fish oil diet
      administration, metabolic syndrome rats had a significant reduction in blood
      pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and
      total lipids, but no change was observed in TNF-alpha concentration or fat
      accumulation. In conclusion, fish oil reversed the alterations on metabolic
      parameters and blood pressure exerted by sucrose administration, although it had
      no effect on TNF-alpha production and adiposity. This confirms the theory that
      the molecular etiology of the metabolic syndrome is multifactorial, as is the
      effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and
      multifaceted actions.

PMID- 15157942
TI  - Fish oil supplementation in F1 generation associated with naproxen, clenbuterol,
      and insulin administration reduce tumor growth and cachexia in Walker 256 tumor
      bearing rats.
AB  - Weanling female Wistar rats were supplemented with fish oil (1 g/kg body weight)
      for one generation. The male offspring received the same supplementation until to
      adult age. Rats supplemented with coconut fat were used as reference. Some rats
      were inoculated subcutaneously with a suspension (2 x 10(7) cells/mL) of Walker
      256 tumor. At day 3, when the tumor was palpable, rats were treated with naproxen
      (N) (0.1 mg/mL), clenbuterol (Cb) (0.15 mg/kg body weight), and insulin (I) (10
      U/kg body weight). At day 14 after tumor inoculation, the animals were killed.
      Tumor was removed and weighed. Blood, liver, and skeletal muscles were also
      collected for measurements of metabolites and insulin. In both tumor-bearing
      untreated rats and tumor-bearing rats supplemented with coconut fat, tumor
      growth, triacylglycerol, and blood lactate levels were higher, and glycogen
      content of the liver, blood glucose, cholesterol and HDL-cholesterol levels were
      lower as compared with the non-tumor-bearing and fish oil supplemented groups.
      Fish oil supplementation of tumor-bearing rats led to a partial recovery of the
      glycogen content in the liver and a full reversion of blood glucose, lactate,
      cholesterol, and HDL-cholesterol levels. The treatment with N plus Cb plus I
      attenuated cancer cachexia and decreased tumor growth in both coconut fat and
      fish oil supplemented rats. In conclusion, chronic fish oil supplementation
      decreased tumor growth and partially recovered cachexia. This beneficial effect
      of fish oil supplementation was potentiated by treatment with naproxen plus
      clenbuterol plus insulin.

PMID- 15157943
TI  - Iron deficiency in the pregnant rat has differential effects on maternal and
      fetal copper levels.
AB  - Iron deficiency during pregnancy causes problems both for the mother and fetus.
      Iron deficiency is known to have secondary effects on copper metabolism. In this
      study, we use a rat model to examine the effect of iron deficiency on copper
      levels in maternal and fetal tissue. We assess whether the effects of iron
      deficiency on copper metabolism are due to alterations in mRNA levels of proteins
      of copper transport. Rowett Hooded Lister rats were fed diets with four different
      iron contents before and during pregnancy. Maternal and fetal samples were
      collected on day 21 of gestation. Copper and iron levels of liver and placenta
      were analyzed, mRNA levels of genes involved in copper transport were studied,
      and copper oxidase activity measured. Reduced dietary iron was found to increase
      maternal liver copper, inversely correlating with iron levels. Correspondingly,
      copper and ceruloplasmin increased in maternal serum. The placenta showed the
      greatest increase in copper levels. As the iron content of the maternal diet
      decreased so did the iron and copper levels in the fetal liver. In all tissues
      examined, mRNA expression for CTR1, ATOX1, ATP7A, and ATP7B was unchanged by iron
      deficiency. However, copper oxidase activity in maternal serum and placenta was
      increased. Our study in a rat model demonstrates that iron deficiency during
      pregnancy has a differential effect on copper metabolism in the mother and fetus.
      It is clear from this study that the changes in copper levels that accompany iron
      deficiency are not mediated by changes in transcription of the genes involved in
      copper transport.

PMID- 15157944
TI  - Effects of garlic extract consumption on blood lipid and oxidant/antioxidant
      parameters in humans with high blood cholesterol.
AB  - Effects of garlic extract supplementation on blood lipid profile and
      oxidant/antioxidant status were investigated in volunteer subjects with high
      blood cholesterol. A total of 23 volunteer subjects with high blood cholesterol
      (>5.98 mmol/L) participated in the study. Of them, 13 patients were evaluated as
      a hypertensive group and the others a normotensive group. Before (first sample)
      and after (second sample) garlic extract consumption for 4 months, routine blood
      analyses including lipid parameters and liver and kidney function tests were
      performed. Additionally, blood oxidant (malondialdehyde [MDA], oxidation
      resistance [OR]), and antioxidant (antioxidant potential [AOP], nonenzymatic
      superoxide radical scavenger activity [NSSA]) parameters were measured. Serum
      total cholesterol, low-density lipoprotein (LDL) and very-low-density lipoprotein
      (VLDL) cholesterols, and triglyceride levels were found to be significantly
      lowered, but HDL high-density lipoprotein cholesterol level increased after the
      extract use. The total:HDL cholesterol ratio was also found to be significantly
      decreased after the extract use. There were no meaningful differences with regard
      to other routine biochemical parameters. Additionally, blood AOP, OR, and NSSA
      values were found increased and MDA level decreased in the second samples
      relative to the first ones. Systolic and diastolic blood pressure values were
      also found to be significantly lowered after extract supplementation in the
      hypertensive group, but no similar changes were observed in the normotensive
      group. We conclude that garlic extract supplementation improves blood lipid
      profile, strengthens blood antioxidant potential, and causes significant
      reductions in systolic and diastolic blood pressures. It also leads to a decrease
      in the level of oxidation product (MDA) in the blood samples, which demonstrates
      reduced oxidation reactions in the body.

PMID- 15157945
TI  - Cytokines and sleep: the first hundred years.

PMID- 15157946
TI  - Sleep apnea: a model for studying cytokines, sleep, and sleep disruption.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, characterized
      by repeated disruptions of breathing during sleep. The sleep fragmentation and
      accompanying hypoxemia lead to many negative consequences including cardiac
      arrhythmias, nocturnal hypertension, confusion, cognitive impairment, daytime
      sleepiness, as well as depressive symptoms. From the perspective of
      psychoneuroimmunology (PNI), OSA holds promise as a model for studying sleep and
      cytokines because of its many relevant characteristics, including neuroimmune
      interactions, mood changes, and behaviors that directly affect the course of the
      disorder. In this minireview we briefly summarize the existing literature on
      cytokines and sleep and then discuss work on cytokines and OSA. We believe that
      the study of OSA presents researchers with an excellent opportunity to tease
      apart the many complex and interwoven components of sleep that are relevant to
      PNI.

PMID- 15157947
TI  - Pain, psychological variables, sleep quality, and natural killer cell activity in
      midlife women with and without fibromyalgia.
AB  - In women with fibromyalgia (FM), central nervous system (CNS) dysfunction in
      pain, mood, and sleep processes could be associated with changes in immune system
      indicators. The primary purpose of this study was to compare pain, psychological
      variables, subjective and objective sleep quality, lymphocyte phenotypes and
      activation markers, and natural killer activity (NKA) in midlife women with and
      without FM. A secondary purpose was to explore relationships among these
      variables in a step-wise regression. Subjects had pain pressure tender points
      assessed, completed a psychiatric interview and questionnaires (Beck Depression
      Inventory, SCL-90, Profile of Mood States, subjective sleep), and underwent
      polysomnograhic assessment for two consecutive nights. Lymphocyte phenotypes,
      activation markers, and NKA were assessed from blood drawn the morning after
      sleep laboratory night 2. Compared to controls, women with FM had lower pain
      thresholds, more psychological distress, higher depression scores, and reduced
      subjective and objective sleep quality. They also had fewer NK cells (p <.009)
      and more NK cells that expressed the IL-2 receptor (p <.04), but these
      differences were not statistically significant after correction for multiple
      comparisons. NKA was not statistically significantly lower in the women with FM
      compared to controls. In a multiple regression of age, tender point threshold,
      depression, psychological distress, and sleep efficiency, only the effect of
      group was significant (F = 5.479, p <.03) on NKA. In conclusion, we found little
      evidence to support the hypothesis that pain, mood, and sleep symptoms are
      associated with changes in the enumeration of peripheral lymphocytes or function
      in FM.

PMID- 15157948
TI  - Basal circadian and pulsatile ACTH and cortisol secretion in patients with
      fibromyalgia and/or chronic fatigue syndrome.
AB  - The objective of this study was to evaluate and compare the basal circadian and
      pulsatile architecture of the HPA axis in groups of patients with FMS, CFS, or
      both syndromes with individually matched control groups. Forty patients with
      either FMS (n = 13), FMS and CFS (n = 12), or CFS (n = 15) were matched by age
      (18-65), sex, and menstrual status to healthy controls. Subjects were excluded if
      they met criteria for major Axis I psychiatric disorders by structured clinical
      interview (SCID). Subjects were admitted to the General Clinical Research Center
      where meals and activities were standardized. Blood was collected from an
      intravenous line every 10 min over 24 h for analysis of ACTH and cortisol.
      Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37
      subject pairs. There was a significant delay in the rate of decline from
      acrophase to nadir for cortisol levels in patients with FMS (P <.01). Elevation
      of cortisol in the late evening quiescent period was evident in half of the FMS
      patients compared with their control group, while cortisol levels were
      numerically, but not significantly, lower in the overnight period in patients
      with CFS compared with their control group. Pulsatility analyses did not reveal
      statistically significant differences between patient and control groups. We
      conclude that the pattern of differences for basal circadian architecture of HPA
      axis hormones differs between patients with FMS and CFS compared to their matched
      control groups. The abnormalities in FMS patients are consistent with loss of HPA
      axis resiliency.

PMID- 15157949
TI  - Exploring the cytokine and endocrine involvement in narcolepsy.
AB  - Narcolepsy is a disabling neurological sleep disorder characterized by excessive
      daytime sleepiness and abnormal REM sleep manifestations. Recently, the role of
      cytokines and growth hormone in the regulation of sleep and narcolepsy has been
      considered, and data suggest that proinflammatory cytokines may be involved in
      sleep and narcoleptic symptoms. Serum and clinical data were obtained from the
      Stanford Center for Narcolepsy Research for 39 Narcoleptics (22 Females, 17
      Males, age 39+/-14.9) and 40 controls (13 Females, 27 Males, age 46+/-17.9).
      Plasma levels of TNF-alpha, IL-6, and human growth hormone (hGH) were measured by
      ELISA. TNF-alpha and IL-6 were significantly increased in narcoleptic subjects
      compared to controls (p=.001). Interestingly, hGH was significantly increased in
      narcoleptic subjects (p <.0001). There was also a significant difference in the
      epworth sleepiness scale (ESS) (17.7+/-4.6 vs. 5.5+/-3.2, p <.0001). These data
      indicate that narcoleptics, relative to controls, had higher serum levels of TNF
      alpha, IL-6, and hGH. These data suggest that the dysregulation of sleep observed
      in narcoleptics correlates with the immune and endocrine dysregulation seen in
      these subjects, and the observed changes may in fact contribute to the higher
      likelihood of disturbed sleep and/or increased incidence of infection. Additional
      work is required to fully characterize connections between cytokines and
      narcoleptic symptomatology.

PMID- 15157950
TI  - Cellular adhesion molecule expression, nocturnal sleep, and partial night sleep
      deprivation.
AB  - Sleep is hypothesized to have a role in the regulation of the immune system. This
      study evaluated the nocturnal expression of cellular adhesion molecules, Mac-1
      and L-selectin on monocytes and lymphocytes during a full nights sleep and
      following a partial night of sleep deprivation (PSD). Healthy male subjects
      (n=16) had an increase in the percentage of Mac-1 positive lymphocytes across the
      baseline night. Whereas, the percentage of Mac-1 positive lymphocytes was reduced
      and L-selectin positive lymphocytes and monocytes were greater during the PSD
      night as compared to the baseline night. These data indicate that acute sleep
      disruption is associated with alterations in cellular adhesion molecule
      expression, with implications for the regulation of immune cell trafficking.

PMID- 15157951
TI  - Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans.
AB  - Recent human studies suggested a supportive influence of regular nocturnal sleep
      on immune responses to experimental infection (vaccination). We hypothesized here
      that sleep could ease such responses by shifting the balance between T helper 1
      (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby
      favoring cellular over humoral responses to infection. We compared the Th1/Th2
      cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00
      and 07:00 h) and while remaining awake during the same nocturnal interval, in a
      within-subject cross-over design. Blood was collected every 2 h. Production of T
      cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2),
      interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--was measured
      at the single cell level using multiparametric flow cytometry. Also, several
      immunoactive hormones--prolactin, growth hormone (GH), thyroid stimulating
      hormone (TSH), cortisol, and melatonin--were measured, the release of which is
      known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep
      induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity,
      as indicated by an increased (p <.05) ratio of IFN-gamma/IL-4 producing T helper
      cells. However, the Th1 shift was only of moderate size and replaced by Th2
      dominance during late sleep (p <.05). It could be mediated via release of
      prolactin and GH which both were distinctly increased during sleep (p <.001).
      Though unexpected, the most pronounced effect of sleep on T cell cytokine
      production was a robust decrease in TNF-alpha producing CD8+ cells probably
      reflecting increased extravasation of cytotoxic effector and memory T cells.

PMID- 15157952
TI  - Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent
      African American alcoholics.
AB  - Animal studies reveal that cytokines play a key role in the regulation of sleep.
      Alcoholic patients show profound alterations of sleep and a defect in the
      homeostatic recovery of sleep following sleep loss. In this study, we
      investigated whether nocturnal plasma levels of interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF) were associated with disordered sleep in alcohol
      dependence by testing the temporal relationships between these inflammatory
      cytokines and sleep, before and after sleep deprivation. All-night
      polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 h were
      conducted across baseline, partial sleep deprivation, and recovery nights in
      abstinent African American alcoholics (n=16) and matched controls (n=15). Coupled
      with prolonged sleep latency and increased rapid eye movement sleep, alcoholics
      showed nocturnal elevations of IL-6 and TNF as compared to controls after
      adjustment for alcohol consumption and body mass index. Following sleep
      deprivation, alcoholics showed greater nocturnal levels of IL-6 and greater
      nocturnal increases of TNF as compared to controls. Pre-sleep IL-6 levels at
      23:00 h correlated with prolonged sleep latency after adjustment for potential
      confounders whereas IL-6 levels at 03:00 h correlated with rapid eye movement
      sleep in the second half of the night. Taken together, these findings indicate
      that circulating levels of proinflammatory cytokines may have a negative
      influence on sleep initiation. These findings have implications for determining
      why sleep is disordered in alcoholics and may aid in the development of novel
      treatments to optimize sleep in this population.

PMID- 15157953
TI  - Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in
      healthy volunteers.
AB  - There is very little published information on the diurnal variation of cytokines
      and their receptors, in healthy individuals during normal sleep-wake patterns or
      during sustained wakefulness. The aim of the current investigation was to
      characterize concentrations of soluble tumor necrosis factor receptors (sTNF-Rs)
      and interleukin-2 receptor (sIL-2R) during normal sleep and wakefulness, as well
      as during a 24 h vigil. Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R
      did not differ significantly between nocturnal sleep and nocturnal wakefulness.
      Rhythmic analysis (2-h intervals) revealed significant diurnal variations for
      both sTNF-R p55 and sTNF-R p75, but not levels of sIL-2R. Diurnal variations of
      both sTNF-Rs were characterized by a single cosine curve with an average peak
      near 06:00 h in the morning. This peak occurred well before that of cortisol, and
      fluctuated inversely with the diurnal rhythm of temperature. These diurnal
      variations in sTNF-Rs levels are consistent with the hypothesis that the TNF
      system plays a role in normal diurnal temperature regulation.

PMID- 15157954
TI  - A regulatory role of prolactin, growth hormone, and corticosteroids for human T
      cell production of cytokines.
AB  - The release of the pituitary hormones, prolactin and growth hormone (GH), and of
      adrenal corticosteroids is subject to a profound regulation by sleep. In addition
      these hormones are known to be involved in the regulation of the immune response.
      Here, we examined their role for in vitro production of T-cell cytokines.
      Specifically, we hypothesized that increased concentrations of prolactin and GH
      as well as a decrease in cortisol, i.e., hormonal changes characterizing early
      nocturnal sleep, could be responsible for a shift towards T helper 1 (Th1)
      cytokines during this time. Whole blood was sampled from 15 healthy humans in the
      morning after regular sleep and was activated in vitro with ionomycin and two
      concentrations of phorbol myrestate acetate (PMA, 8 and 25 ng/ml) in the absence
      or presence of prolactin, prolactin antibody, GH, glucocorticoid receptor (GR)
      antagonist RU-486, or mineralocorticoid receptor (MR) antagonist spironolactone.
      Hormones were examined at physiological concentrations. Production of T-cell
      derived cytokines was measured at the single cell level using multiparametric
      flow cytometry. Generally, effects were more pronounced after stimulation with 8
      rather than 25 ng/ml PMA. The following changes reached significance (p <.05):
      prolactin (versus prolactin antibody) increased tumor necrosis factor-alpha (TNF
      alpha) and interferon-gamma (IFN-gamma) producing CD4+ and CD8+ cells and
      interleukin-2 (IL-2) producing CD8+ cells. Compared with control, prolactin
      antibody decreased, whereas GH increased IFN-gamma+CD4+ cells. RU-486 increased
      TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. Surprisingly strong
      effects were found after MR blocking with spironolactone which increased TNF
      alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. No effects on IL-4+CD4+
      cells were observed, while the IFN-gamma/IL-4 ratio shifted towards Th1 after
      spironolactone and after RU-486 plus GH. Results suggest that enhanced prolactin
      and GH concentrations as well as low cortisol levels during early nocturnal sleep
      synergistically act to enhance Th1 cytokine activity.

PMID- 15157955
TI  - Macrophage participation in influenza-induced sleep enhancement in C57BL/6J mice.
AB  - Mice develop changes in sleep during the nonspecific immune response that occurs
      during the initial few days after inoculation with influenza virus. T
      lymphocytes, neutrophils, macrophages, and natural killer (NK) cells all
      participate in the early host response to influenza infection. All of these cell
      types are potential sources of endogenous substances that modulate sleep, but the
      contributory role of each cell type to the alteration of somnolence during
      infection has not been determined. To investigate which cell types contribute to
      the sleep enhancement that develops during influenza infection in mice, the sleep
      patterns of C57BL/6J mice with perturbations of particular facets of host immune
      response capabilities were assessed before and after influenza infection.
      Targeted mutation of the gene Ccl3 (macrophage inflammatory protein 1 alpha)
      prevented development of the dark phase sleep enhancement that is characteristic
      of C57BL/6J mice after influenza infection. Other experimental treatments that
      impair macrophage or monocyte function also produced significant (administration
      of pentoxifylline or CNI-1493) or marginally significant (deletion of the
      interferon-gamma gene or intranasal administration of carrageenan) changes in
      influenza-induced sleep enhancement in C57BL/6J mice. In contrast, functional
      impairments of NK cells, neutrophils, and T lymphocytes did not significantly
      influence sleep responses. These data therefore support a contributory role for
      macrophages, but not for NK cells, neutrophils, and T lymphocytes, in eliciting
      the sleep response typical of influenza-infected C57BL/6J mice.

PMID- 15157957
TI  - Sleep, but not febrile responses of Fisher 344 rats to immune challenge are
      affected by aging.
AB  - Sleep is altered in response to infection and immune challenge in humans and non
      human animals. Although there are changes in sleep and facets of immune function
      with aging, sleep responses of aged subjects to immune challenge have received
      little, if any attention. To test the hypothesis that aging affects sleep
      responses to immune challenge, intracerebroventricular injections of interleukin
      1 (IL-1) were given to young and aged rats and subsequent sleep-wake behavior was
      determined. Under basal conditions and in the absence of an immune challenge,
      sleep patterns of young (3 months) and aged (25-27 months) Fisher 344 rats did
      not differ. In young animals, IL-1 (2.5 ng) enhanced non-rapid eye movement
      (NREM) sleep, inhibited rapid eye movement (REM) sleep, and induced fever. In
      aged animals, IL-1 administration did not alter NREM sleep, but REM sleep was
      inhibited and brain temperature increased to the same extent observed in young
      animals. These results show that alterations in sleep following immune challenge
      are impacted by aging, whereas febrile responses are not. Since it has been
      postulated that enhanced NREM sleep may facilitate recovery from microbial
      infection, the present results also suggest that the lack of NREM sleep responses
      of aged rats to immune challenge may contribute to the increased infection
      induced morbidity and mortality of aged organisms.

PMID- 15157956
TI  - The role of nitric oxide synthases in the sleep responses to tumor necrosis
      factor-alpha.
AB  - It is well established that cytokines such as tumor necrosis factor-alpha
      (TNFalpha) and interleukin-1beta (IL-1beta) are involved in physiological sleep
      regulation, yet their downstream somnogenic mechanisms remain largely
      uninvestigated. Nitric oxide (NO) is an effector molecule for some TNFalpha
      actions. Neuronal nitric oxide synthase (nNOS) and inducible nitric oxide
      synthase (iNOS) gene knockout (KO) mice sleep differently than their respective
      controls. In this study, we tested the hypothesis that NO mediates TNFalpha
      induced sleep using iNOS and nNOS KO mice and their corresponding wild-type
      controls. Systemic administration of TNFalpha increased non-rapid eye movement
      sleep (NREMS) in the two control strains and in the iNOS KO mice during the first
      4 h post-injection but failed to increase NREMS in nNOS KO mice. Rapid eye
      movement sleep (REMS) was suppressed by TNFalpha in nNOS controls but not in the
      other strains examined. The results suggest that TNFalpha affects sleep, in part,
      through nNOS.

PMID- 15157958
TI  - Dose and time-dependent protection of the antioxidant N-L-acetylcysteine against
      impulse noise trauma.
AB  - Noise-induced hearing loss is one of the most common causes of hearing
      disability, and at present there is no effective biological protection or cure.
      Firearms and some industrial equipment can generate very high levels of impulse
      noise, which is known to cause sensorineural hearing loss. It has been shown that
      antioxidants such as N-L-acetylcysteine (NAC) can protect the inner ear from
      oxidative damage. The present study investigates whether NAC (i.p.) can protect
      the cochlea from impulse noise trauma. Rats were exposed to 50 noise pulses at
      160 dB SPL peak value. Electrophysiological hearing thresholds were assessed with
      auditory brainstem response (ABR) up to 4 weeks after noise exposure. Animals
      exposed to impulse noise, without treatment of NAC, had larger threshold shifts
      in the frequency range 4-40 kHz than animals injected with NAC. Hair cell loss
      was significantly reduced using a schedule of three NAC injections in the rats.
      These results suggest that NAC can partially protect the cochlea against impulse
      noise trauma.

PMID- 15157959
TI  - Unique responses of auditory cortex networks in vitro to low concentrations of
      quinine.
AB  - The anti-malarial drug quinine has several side effects including tinnitus. The
      aim of the study was to determine if cultured auditory networks growing on
      microelectrode arrays exhibited unique dynamic states when exposed to quinine.
      Eight auditory cortex networks (ACN), eight frontal cortex networks (FCN), and
      five inferior colliculus networks (ICN) were used in this study. Response of ACNs
      to quinine was biphasic, with an excitatory phase followed by inhibition. FCNs
      and ICNs revealed only inhibitory responses. The concentrations at which the
      spike rate was inhibited by 50% (IC50 mean +/- SE) were 42.5 +/- 3.9, 28.7 +/-
      4.8 and 23.9 +/- 2.1 microM for ACNs, FCNs, and ICNs, respectively. Quinine
      increased the regularity and coordination of bursting in all three tissues. The
      increased burst pattern regularity of ICNs coupled with the excitatory responses
      seen only in ACNs between 1 and 10 microM show a unique susceptibility of
      auditory tissues to quinine that may be related to the underlying mechanism that
      triggers tinnitus-like activity.

PMID- 15157960
TI  - Ensemble spontaneous activity in the guinea-pig cochlear nerve.
AB  - Spectral analysis of electrical noise recorded from the round window (RW) of the
      cochlea is referred to as the ensemble spontaneous activity (ESA) of the cochlear
      nerve. The ESA is considered to represent the summed spontaneous activity of
      single fibers of the auditory nerve and changes in the spectral characteristics
      of the ESA have been observed in humans with tinnitus. Experiments were
      undertaken to determine the relationship of the ESA to auditory
      neurotransmission. The ESA consisted of energy centered at approximately 900 Hz,
      similar to the spectral peak of single auditory neuron discharges. The amplitude
      of the ESA was correlated with good auditory sensitivity in the 12-30 kHz region
      of the cochlea. Constant pure tones of 12-22 kHz suppressed the ESA reducing its
      amplitude in a frequency and intensity dependent manner implying that the ESA
      recorded at the RW is generated or dominated by neurons in the basal region of
      the cochlea. The ESA was significantly suppressed by round window perfusion of
      the P2X receptor agonist adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) (10 mM)
      the glutamate receptor antagonist 6-7-dinitroquinoxaline-2,3-dione (DNQX) (1 mM),
      and the sodium channel antagonist tetrodotoxin (TTX) (20 microM). Following
      intravenous furosemide injection (40 mg/kg) reduction and recovery of the ESA
      correlated with similar changes in the endocochlear potential (EP). Following
      DNQX and ATPgammaS an additional spectral peak at 200 Hz was often observed. This
      peak has been postulated to be a correlate of tinnitus in humans but had not
      previously been observed in a guinea-pig model of tinnitus. These data confirm
      the spectral characteristics of the ESA in guinea-pigs and show it is dependent
      on the sensitivity of the auditory nerve and intact auditory neurotransmission.
      In addition these experiments support the view that the ESA represents summed
      spontaneous neural activity in the cochlea and provide a platform for studies of
      the influence of ototoxic compounds on the spontaneous neural outflow of the
      cochlea as a model of tinnitus.

PMID- 15157961
TI  - Acoustomechanical properties of open TTP titanium middle ear prostheses.
AB  - OBJECTIVE: The purpose of the study was to identify acoustcomechanical properties
      of various biostable and biocompatible materials to create a middle ear
      prosthesis with the following properties: (i) improved handling including a good
      view of the head of the stapes or footplate and adjustable length, (ii) improved
      acoustical characteristics that are adequate for ossiculoplastic. The identified
      material should serve to build CE and FDA approved prostheses for clinical use in
      patients. METHODS: Test models made of Teflon, polyetheretherketone,
      polyethylenterephtalate, polysulfone, gold, Al2O3 ceramics, carbon and titanium
      were investigated for their potential to fulfill the requirements. Acoustical
      properties were investigated by laser Doppler velocimetry (LDV) in mechanical
      middle ear models (MMM). Measured data were fed in to a recently created computer
      model of the middle ear (multibody systems approach, MBS). Using computer-aided
      design (CAD) measured and computed data allowed creation and fine precision of
      titanium prostheses (Tubingen Titanium Protheses, TTP). Their handling was tested
      in temporal bones. Acoustomechanical properties were investigated using the MBS
      and mechanical middle ear models. MAIN OUTCOME MEASURES: Input impedance, mass,
      stiffness, and geometry of test models and prostheses were determined.
      Furthermore, their influence on the intraprosthetic transfer functions and on
      coupling to either tympanic membrane or stapes was investigated. RESULTS: Final
      results were FDA- and CE-approved filigreed titanium prostheses with an open head
      that fulfilled the four requirements detailed above. The prostheses (TTP) were
      developed in defined lengths of between 1.75 and 3.5 mm (partial) and 3.0 and 6.5
      mm (total) as well as in adjustable lengths (TTP-Vario). CONCLUSIONS: The results
      suggest acoustomechanical advantages of TTPs because they combine a significantly
      low mass with high stiffness. In contrast to closed prostheses, the open head and
      filigreed design allow an excellent view of the prosthesis foot during coupling
      to the head or footplate of stapes, contributing to an improved intraoperative
      reliability of prosthesis coupling.

PMID- 15157962
TI  - Evaluation of cochlear function in an acute endolymphatic hydrops model in the
      guinea pig by measuring low-level DPOAEs.
AB  - During and after microinjection of artificial endolymph into scala media of the
      guinea pig, the 2f1- f2 -DPOAE at 4.5 kHz generated by low-level primaries was
      recorded. Reproducible changes were measured when 1.1 microl of artificial
      endolymph was injected at a rate of 1.65 nl/s (1.53-1.83). This volume
      corresponds with an acute endolymphatic hydrops of 23%. After the onset of
      injection the inner ear pressure immediately increased to a mean higher level of
      22 Pa, whereas the 2f1- f2 -amplitude and -phase did not change for about 1 min.
      Thereafter, the amplitude decreased 2.6 dB (+/- 0.7) on average and slowly
      regained almost its initial value, with recovery frequently starting within the
      period of injection. In an attempt to explain the observed changes in 2f1- f2 
      amplitude the basilar membrane displacement towards scala tympani at the 2f1- f2
      generation site is estimated to be 19 nm for a 1.1 microl increase of endolymph
      volume. A small deflection of the outer hair cell stereocilia and as a
      consequence a change in cell conductance may explain the 2f1- f2 -amplitude
      changes. However, the precise mechanism of cochlear function change caused by
      endolymph volume increase (hydrops) remains to be elucidated.

PMID- 15157963
TI  - Mechanical properties of sensory and supporting cells in the organ of Corti of
      the guinea pig cochlea--study by atomic force microscopy.
AB  - Mammalian hearing is refined by amplification of the motion of the cochlear
      partition. To understand the cochlear amplification, mechanical models of the
      cochlea have been used. When the dynamic behavior of the cochlea is analyzed by a
      model, elastic properties of the cells in the organ of Corti must be determined
      in advance. Recently, elastic properties of outer hair cells (OHCs) and pillar
      cells have been elucidated. However, those of other cells have not yet been
      clarified. Therefore, in this study, using an atomic force microscope (AFM),
      elastic properties of Hensen's cells, Deiters' cells and inner hair cells (IHCs)
      in the apical turn and those in the basal and second turns were estimated. As a
      result, slopes indicative of cell elastic properties were (8.9 +/- 5.8) x 10(3)
      m(-1) for Hensen's cells (n = 30), (5.5 +/- 5.3) x 10(3) m(-1) for Deiters' cells
      (n = 20) and (3.8 +/- 2.6) x 10(3) m(-1) for IHCs (n = 20), and Young's modulus
      were 0.69 +/- 0.45 kPa for Hensen's cells and 0.29 +/- 0.20 kPa for IHCs. There
      was no significant difference between elastic properties of each type of cell in
      the apical turn and those in the basal and second turns. However, it was found
      that there is a significant difference between Young's moduli of cells estimated
      in this study and those of the OHCs and pillar cells reported previously.

PMID- 15157964
TI  - Round window gentamicin application: an inner ear hair cell damage protocol for
      the mouse.
AB  - It is important to develop an inner ear damage protocol for mice that avoids
      systemic toxicity and produces damage in a relatively rapid fashion, allowing for
      study of early cellular and molecular mechanisms responsible for hair cell death
      and those that underlie the lack of hair cell regeneration in mammals. Ideally,
      this damage protocol would reliably produce both partial and complete lesions of
      the sensory epithelium. We present a method for in vivo induction of hair cell
      damage in the mouse via placement of gentamicin-soaked Gelfoam in the round
      window niche of the inner ear, an adaptation of a method developed to study hair
      cell regeneration in chicks. A total of 82 subjects underwent the procedure.
      Variable doses of gentamicin were used (25, 50, 100 and 200 microg). Saline
      soaked Gelfoam, sham-operations and the contralateral, non-operated cochlea were
      used as controls. Survival periods were 1, 3 and 14 days. Damage was assessed on
      scanning electron microscopy. We found that this method produces relatively rapid
      hair cell damage that varies with dose and can extend the entire length of the
      sensory epithelium. In addition, this protocol produces no systemic toxicity and
      preserves the contralateral ear as a control.

PMID- 15157965
TI  - The Digital Cytocochleogram.
AB  - The Mouse Cochlea Database (MCD) is a collection of resources that include
      digital images and bibliographic information on the mouse cochlea and is
      available at: http://mousecochlea.ccgb.umn.edu. The purpose of this communication
      is to report on the development of one MCD resource: the Digital Cytocochleogram.
      A cytocochleogram is a graphic representation of the anatomical state of the hair
      cells along the complete width and length of the organ of Corti. The Digital
      Cytocochleogram provides Internet users with a complete collection of digital
      images of one or more surface preparations of the mouse organ of Corti from which
      morphometric information can be obtained. By moving a mouse driven, screen cursor
      over a digital image, the location and approximate frequency region of the
      anatomical structure is displayed. Users can also measure the straight-line
      distance between any two structures on the image. The Digital Cytocochleogram
      resource uses two software programs, the Coordinate Finder and Viewer, which are
      written as CGI scripts. The Coordinate Finder program maps each digital image to
      an X,Y coordinate system. The total length of the organ of Corti from all tissue
      segments is computed using an arc-distance approximation formula, with the
      lateral border of the inner pillar cell headplates serving as a trace line or
      reference location. After all of the digital images of the tissue segments are
      mapped, they are placed on the MCD Website where users can use the Viewer program
      to view and morphometrically assess structures using a web browser. A single,
      complete surface preparation from a normal mouse is presently available on the
      MCD website. As the MCD grows, additional images of surface preparations at
      different magnifications from normal, mutant, and experimentally altered mouse
      cochleas will become available.

PMID- 15157966
TI  - Sex differences in distortion product otoacoustic emissions as a function of age
      in CBA mice.
AB  - Age-related hearing loss--presbycusis--is the number one communication problem of
      the aged. A major contributor to presbycusis is the progressive degeneration of
      cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions
      (DPOAEs) are effective in vivo, physiological measures of hearing, assessing the
      health and functioning of the OHCs in mammals. We and others have previously
      demonstrated that DPOAE amplitudes decline with age in humans and mice. The
      present study's objective was to measure age-related declines in the OHCs in CBA
      mice (slow, progressive age-related hearing loss) by comparing DPOAEs and
      auditory brainstem responses (ABRs) generated from females and males. Young adult
      (2.1-2.9 months) and middle-aged CBA (14.0-16.4 months) mice were tested, as well
      as old CBAs (24.3-29.0 months). DPOAE-grams were obtained with L1 = 65 and L2 =
      50 dB SPL, f1/f2 = 1.25, using eight points per octave covering a frequency range
      from 5.6 to 44.8 kHz (geometric mean frequency). ABRs ranged from 3 to 48 kHz.
      Analyses revealed that DPOAE levels decreased with age for middle-aged and old
      male CBAs, but for female CBAs, declines did not occur until old age - after
      menopause. In contrast, ABR amplitudes for female and male young adult and middle
      aged CBAs were the same. Female ABR thresholds were lower than males for old
      CBAs. In conclusion, we discovered that pre-menopausal CBA female mice have
      healthier OHCs relative to middle-aged males, but much of this relative advantage
      is lost post-menopause. Understanding sex differences in age-related sensory
      disorders will be quite helpful for the goals of preventing, slowing or curing
      sensory problems in old age for both women and men.

PMID- 15157967
TI  - Effects of masker component phase on the forward masking produced by complex
      tones in normally hearing and hearing-impaired subjects.
AB  - For normally hearing subjects, harmonic complex tones that give "peaky" waveforms
      on the basilar membrane (Schroeder-positive phase, sine phase or cosine phase)
      lead to less forward masking than complex tones that give less peaky waveforms
      (Schroeder-negative phase or random phase), but have the same power spectrum.
      This difference has been attributed mainly to the combined effects of peripheral
      compression and suppression, both of which depend on the operation of the active
      mechanism in the cochlea. If this explanation is correct, the phase effect should
      be reduced or absent for subjects with moderate cochlear hearing loss. We
      measured growth-of-masking functions for forward maskers containing the first 40
      harmonics of a 100-Hz fundamental, with components added either in cosine phase
      or random phase, using both normally hearing subjects and subjects with moderate
      cochlear hearing loss. The signal frequency was 1 or 2 kHz. For the normally
      hearing subjects, the mean slopes of the growth-of-masking functions at 1 and 2
      kHz, respectively, were 0.53 and 0.44 for the random-phase masker and 0.31 and
      0.26 for the cosine-phase masker. For high masker levels, the former produced
      considerably more masking than the latter. The phase effect was smaller for the
      hearing-impaired than for the normally hearing subjects, which is consistent with
      the idea that it is partly caused by peripheral compression and suppression.
      However, three of the five hearing-impaired subjects showed a significant effect
      of masker phase for at least one signal frequency. In one case, this occurred
      when the hearing loss at the signal frequency was 65 dB. The slopes of the growth
      of-masking functions were consistently less than one for the hearing-impaired
      subjects. Further testing suggested that the efferent system was not involved in
      producing the phase effect.

PMID- 15157968
TI  - Effect of an initial noise induced hearing loss on subsequent noise induced
      hearing loss.
AB  - The effect of previous noise induced hearing loss (NIHL) on subsequent NIHL was
      studied in rats. Three groups of animals were initially exposed to different
      durations of 113 dB SPL broad band noise (21 days, 3 days or 0 days--unexposed).
      Their permanent threshold shifts (PTS) from this exposure (PTS1) were evaluated
      using auditory nerve-brainstem evoked responses (ABR). All the animals were then
      noise-exposed for an additional 12 days, and the incremental PTS following this
      exposure (PTS2) was also assessed. The 21 day group showed the greater PTS1 [mean
      +/- SD: 27.03 +/- 6.78 dB, compared with 11.67 +/- 10.47 dB (3 day group)] and
      the lowest PTS2 [9.84 +/- 8.19 dB, compared with 13.33 +/- 14.60 dB (3 day group)
      and 24.04 +/- 12.4 dB (0 day group)]. This group also showed the highest total
      PTS and lowest SD following the two noise exposures [36.88 +/- 6.29 dB, compared
      with 25.00 +/- 12.68 dB (3 day group) and 26.35 +/- 11.93 dB (0 day group)]. The
      results may be explained by the lower effective intensity of the second noise
      exposure for the animals with a large PTS1 compared to those with little or no
      NIHL from the first noise exposure.

PMID- 15157969
TI  - Level dependence of distortion product otoacoustic emissions in the leopard frog,
      Rana pipiens pipiens.
AB  - The inner ear of frogs holds two papillae specialized in detecting airborne
      sound, the amphibian papilla (AP) and the basilar papilla (BP). We measured input
      output (I/O) curves of distortion product otoacoustic emissions (DPOAEs) from
      both papillae, and compared their properties. As in other vertebrates, DPOAE I/O
      curves showed two distinct segments, separated by a notch or kneepoint. The slope
      of the low-level segment was conspicuously different between the AP and the BP.
      For DPOAE I/O curves from the AP, slopes were < or = 1 dB/dB, similar to what is
      found in mammals, birds and some lizards. For DPOAE I/O curves from the BP these
      slopes were much steeper (approximately 2 dB/dB). Slopes found at high stimulus
      levels were similar in the AP and the BP (approximately 2 dB/dB). This
      quantitative difference between the low-level slopes for DPOAEs from the AP and
      the BP may signify the involvement of different mechanisms in low-level DPOAE
      generation for the two papillae, respectively.

PMID- 15157970
TI  - Auditory streaming based on temporal structure in hearing-impaired listeners.
AB  - The influence of temporal cues on sequential stream segregation was investigated
      using five elderly hearing-impaired listeners. In experiment 1, an alternating
      pattern of A and B tones was used. Each tone was a harmonic complex with a 100-Hz
      fundamental, with one of three passbands (1250-2500, 1768-3636, or 2500-5000 Hz)
      and one of three component-phase relationships (cosine, alternating, or random).
      The complexes had an overall level of 96 dB SPL. The detection of a change in
      relative timing of the A and B tones was measured in a two-interval-forced-choice
      paradigm. The sequence in one interval remained isochronous while the sequence in
      the other started isochronously but became increasingly irregular with the
      addition of a cumulative delay between the A and B tones. Component phase
      relationship and passband difference both had significant effects on the minimum
      detectable delay, indicating that temporal structure produced obligatory stream
      segregation. In experiment 2, subjects continuously reported whether tones
      presented in a 30-s ABA-ABA- sequence were perceived as segregated or integrated.
      Differences in component phase between A and B significantly increased perceived
      segregation, but passband did not. In conclusion, stream segregation due to
      differences in temporal structure is robust in elderly subjects with cochlear
      hearing loss and comparable to that found previously in young normally hearing
      subjects.

PMID- 15157971
TI  - Interresponse times and the structure of choice.
AB  - This paper presents some analyses of available data on interresponse-time
      emission on concurrent variable-interval schedules arranged either continuously
      or as discrete components, and in which either reinforcer rates or magnitudes
      were varied. Ratios of frequencies of interresponse times in a series of temporal
      bins varied in their sensitivity to reinforcement: Sensitivity values were least
      for interresponse times around 0.2-0.4s, were higher in the region 0-0.2s, and
      were highest at values greater than 0.4s. Relative frequencies of interresponse
      times were greatest around 0.2-1.6s. As a result, time allocation to alternatives
      were mainly determined by IRTs between 0.8 and 6.4s, and least by IRTs less than
      0.8s. If inter-bout times reflect time allocation to unmeasured responses, then
      time spent emitting unmeasured behavior may be the main constituent of time
      allocation on concurrent schedules. An analysis of log survivor plots supported
      this suggestion, and further suggested that a full understanding of time
      allocation in choice requires accepting that unmeasured responses do not result
      from a unitary process, but from many disparate contributing processes. These
      other behaviors can be revealed through Gaussian log-normal analyses of
      interresponse-time distributions.

PMID- 15157972
TI  - Varying initial-link and terminal-link durations in concurrent-chains schedules:
      a comparison of three models.
AB  - In Experiment 1, pigeons responded on concurrent-chains schedules with equal
      variable-interval schedules as initial links and fixed delays to food as terminal
      links. One terminal-link delay was always three times as long as the other. As
      terminal-link delays increased, response percentages on the key with the shorter
      terminal link increased according to a curvilinear function. This result
      supported the predictions of the hyperbolic value-added model and the contextual
      choice theory but not delay-reduction theory. In Experiment 2, the terminal links
      were always delays of 2s and 12s, followed by food, and the durations of the
      initial links varied across conditions. As initial-link durations increased,
      pigeons' response percentages on the key with the shorter terminal link
      decreased, but toward an asymptote greater than 50%, indicating a continued
      preference for the shorter terminal link with very long initial links. This
      result was more consistent with the predictions of the hyperbolic-value added
      model than with those of the contextual-choice model or of delay-reduction
      theory.

PMID- 15157973
TI  - Amount-dependent temporal discounting?
AB  - Amount-dependent temporal discounting has been demonstrated for human choice
      between outcomes differing in amount and delay. In the only study to date with
      non-humans, Grace reported no evidence for amount-dependent temporal discounting
      with pigeons in a concurrent-chains procedure. The present experiments repeated
      Grace's procedure but with modifications to enhance the discrimination between
      small and large magnitude outcomes. In Experiment 1, sensitivity of pigeons'
      initial-link choice to the terminal link delay ratio was greater with large
      reinforcer durations in the terminal links than with small reinforcer durations.
      This result is consistent with a greater rate of temporal discounting for larger
      reinforcers (the reverse of the result for humans), but can also be explained as
      enhanced discrimination of delay ratios with larger reinforcer durations. The
      results of a second experiment supported Grace's conclusion that amount-dependent
      temporal discounting does not characterize pigeons' choice in concurrent chains.
      Because reinforcer amount was held constant between choice alternatives in the
      present experiments and that of Grace, but varied in the human studies, our
      results question whether prior demonstrations of amount-dependent discounting
      reflect the effects of reinforcer delay or of reinforcer amount. Differences in
      the procedures used to study discounting in humans (titration procedures) and non
      humans (concurrent chains) may contribute to the divergent results across
      species.

PMID- 15157974
TI  - Quantitative analyses of methamphetamine's effects on self-control choices:
      implications for elucidating behavioral mechanisms of drug action.
AB  - The purpose of the present research was to utilize quantitative methods to
      identify behavioral mechanisms involved in the effects of stimulant drugs on
      choice in a self-control procedure. A logarithmic equation based upon a
      combination of the matching law and hyperbolic discounting was used to separate
      drug-induced changes in sensitivity to reinforcement delay from drug-induced
      changes in sensitivity to reinforcement amount. Pigeons responded under a
      concurrent-chains schedule. In the initial link, two keys were illuminated
      simultaneously and access to the terminal link was controlled by a single random
      interval (RI) schedule; pecks on one or the other key lead to its terminal link
      with a 0.5 probability. In the terminal links, one alternative provided 1-s
      access to food (the smaller reinforcer) and the other alternative provided 4-s
      access to food (the larger reinforcer). The signaled delay to the smaller
      reinforcer always was 2s, whereas the signaled delay to the larger reinforcer
      increased from 2 to 40s within each session, across 10-min blocks. In general,
      intermediate doses of methamphetamine increased preference for the larger more
      delayed reinforcer. Quantitative analyses indicated that, in most cases,
      methamphetamine decreased sensitivity to reinforcement delay. In a few instances,
      concomitant decreases in sensitivity to reinforcement amount also occurred. These
      results suggest that a reduced sensitivity to reinforcement delay may be
      important behavioral mechanism of the effects of stimulants on self-control
      choices, and that this effect sometimes can be accompanied by a decreased
      sensitivity to reinforcement amount.

PMID- 15157975
TI  - The behavioral economics of consumer brand choice: patterns of reinforcement and
      utility maximization.
AB  - Purchasers of fast-moving consumer goods generally exhibit multi-brand choice,
      selecting apparently randomly among a small subset or "repertoire" of tried and
      trusted brands. Their behavior shows both matching and maximization, though it is
      not clear just what the majority of buyers are maximizing. Each brand attracts,
      however, a small percentage of consumers who are 100%-loyal to it during the
      period of observation. Some of these are exclusively buyers of premium-priced
      brands who are presumably maximizing informational reinforcement because their
      demand for the brand is relatively price-insensitive or inelastic. Others buy
      exclusively the cheapest brands available and can be assumed to maximize
      utilitarian reinforcement since their behavior is particularly price-sensitive or
      elastic. Between them are the majority of consumers whose multi-brand buying
      takes the form of selecting a mixture of economy -- and premium-priced brands.
      Based on the analysis of buying patterns of 80 consumers for 9 product
      categories, the paper examines the continuum of consumers so defined and seeks to
      relate their buying behavior to the question of how and what consumers maximize.

PMID- 15157976
TI  - Why cooperate? An economic perspective is not enough.
AB  - Cooperation is usually explained from an economic perspective focused mainly on
      the tangible outcomes received by individuals that are also dependent on the
      behavior of others, with little reference to the actual behaviors used when
      cooperating. The potential consequences of social dimensions associated with
      cooperative behaviors are minimized in Skinnerian and game-theory models by means
      of anonymous subjects that behave individually while physically isolated in
      separate chambers. When cooperation and non-cooperation occur in the real world,
      however, they are often associated not only with different outcomes but also with
      different behaviors. Unlike non-cooperation, cooperative behaviors are usually
      intrinsically social, influenced by the presence and behaviors of familiar
      partners. Research is described that addresses whether the social dimensions of
      cooperative actions go beyond mere description of behaviors to also explain why
      cooperation occurs. One way to resolve the relative importance of economic and
      social factors for explanations of cooperation is to measure choice between the
      options of cooperation and non-cooperation. The economic perspective, linked to
      models derived from game theory, frames the question as a choice determined by
      differences in tangible outcomes such as food or money that, in evolutionary
      terms, are surrogates for gains in fitness. From a behavioral perspective, the
      choice between cooperation and non-cooperation is also determined by social
      dimensions associated only with cooperation. The influence of social cooperation
      on preference was examined by means of two rectangular chambers interconnected by
      a T-maze. In one chamber, pairs of laboratory rats were reinforced with saccharin
      solution for coordinating back-and-forth shuttling; in the second chamber, a
      single animal was reinforced for back-and-forth shuttling performed in isolation.
      With outcomes equalized between the two options, cooperation was preferred by the
      majority of subjects. Moreover, variation in the relative rate of reinforcement
      during cooperation was not a strong predictor of choice whereas the level of
      intra-pair coordination was positively related to preference. Implications of
      this result are discussed for both method and theory, including the hypothesis
      that the preference is influenced by intrinsic reinforcements evoked by
      cooperating. The consequences for evolutionary fitness would then arise not only
      from tangible outcomes but from the relationships that develop when cooperating
      even when immediate and tangible pay-offs are absent, insufficient or sub
      optimal. The impact of cooperative relationships on fitness may therefore not
      occur immediately but in the future, and perhaps in another context, when they
      influence outcomes that have a significant impact on survival and reproduction.

PMID- 15157977
TI  - Behavior-analytic approaches to decision making.
AB  - Behavior analysis has much to offer the study of phenomena in the area of
      judgement and decision making. We review several research areas that should
      continue to profit from a behavior-analytic approach, including the relative
      merit of contingency-based and rule-governed instruction of solving algebra and
      analogy problems, and the role of conditioned reinforcement and the inter-trial
      interval in a type of Prisoner's Dilemma Game. We focus on two additional areas:
      (1) the study of base-rate neglect, a notorious reasoning fallacy and (2) the
      study of the sunk-cost effect, which characterizes ill-conceived investment
      decisions. In each of these two cases we review studies with humans and pigeons
      as subjects.

PMID- 15157978
TI  - A behavior analysis of absolute pitch: sex, experience, and species.
AB  - Absolute pitch (AP) perception refers to the ability to identify, classify, and
      memorize pitches without use of an external reference pitch. In tests of AP,
      several species were trained to sort contiguous tones into three or eight
      frequency ranges, based on correlations between responding to tones in each
      frequency range and reinforcement. Two songbird species, zebra finches and white
      throated sparrows, and a parrot species, budgerigars had highly accurate AP, they
      discriminated both three and eight ranges with precision. Relative to normally
      reared songbirds, isolate reared songbirds had impaired AP. Two mammalian
      species, humans and rats, had equivalent and weak AP, they discriminated three
      frequency ranges to a lackluster standard and they acquired only a crude
      discrimination of the lowest and highest of eight frequency ranges. In
      comparisons with mammals even isolate songbirds had more accurate AP than humans
      and rats.

PMID- 15157979
TI  - Dissociating explicit and procedural-learning based systems of perceptual
      category learning.
AB  - A fundamental question is whether people have available one category learning
      system, or many. Most multiple systems advocates postulate one explicit and one
      implicit system. Although there is much agreement about the nature of the
      explicit system, there is less agreement about the nature of the implicit system.
      In this article, we review a dual systems theory of category learning called
      competition between verbal and implicit systems (COVIS) developed by Ashby et al.
      The explicit system dominates the learning of verbalizable, rule-based category
      structures and is mediated by frontal brain areas such as the anterior cingulate,
      prefrontal cortex (PFC), and head of the caudate nucleus. The implicit system,
      which uses procedural learning, dominates the learning of non-verbalizable,
      information-integration category structures, and is mediated by the tail of the
      caudate nucleus and a dopamine-mediated reward signal. We review nine studies
      that test six a priori predictions from COVIS, each of which is supported by the
      data.

PMID- 15157980
TI  - Ambiguity, logic, simplicity, and dynamics: Wittgensteinian evaluative criteria
      in peer review of quantitative research on categorization.
AB  - Research on categorization has changed over time, and some of these changes
      resemble how Wittgenstein's views changed from his Tractatus Logico-Philosophicus
      to his Philosophical Investigations. Wittgenstein initially focused on
      unambiguous, abstract, parsimonious, logical propositions and rules, and on
      independent, static, "atomic facts." This approach subsequently influenced the
      development of logical positivism and thereby may have indirectly influenced
      method and theory in research on categorization: much animal research on
      categorization has focused on learning simple, static, logical rules
      unambiguously interrelating small numbers of independent features. He later
      rejected logical simplicity and rigor and focused instead on Gestalt ideas about
      figure-ground reversals and context, the ambiguity of family resemblance, and the
      function of details of everyday language. Contemporary contextualism has been
      influenced by this latter position, some features of which appear in contemporary
      empirical research on categorization. These developmental changes are illustrated
      by research on avian local and global levels of visual perceptual analysis,
      categorization of rectangles and moving objects, and artificial grammar learning.
      Implications are described for peer review of quantitative theory in which
      ambiguity, logical rigor, simplicity, or dynamics are designed to play important
      roles.

PMID- 15157981
TI  - Molar and molecular views of choice.
AB  - The molar and molecular views of behavior are not different theories or levels of
      analysis; they are different paradigms. The molecular paradigm views behavior as
      composed of discrete units (responses) occurring at moments in time and strung
      together in chains to make up complex performances. The discrete pieces are held
      together as a result of association by contiguity. The molecular view has a long
      history both in early thought about reflexes and in associationism, and, although
      it was helpful to getting a science of behavior started, it has outlived its
      usefulness. The molar view stems from a conviction that behavior is continuous,
      as argued by John Dewey, Gestalt psychologists, Karl Lashley, and others. The
      molar paradigm views behavior as inherently extended in time and composed of
      activities that have integrated parts. In the molar paradigm, activities vary in
      their scale of organization--i.e., as to whether they are local or extended--and
      behavior may be controlled sometimes by short-term relations and sometimes by
      long-term relations. Applied to choice, the molar paradigm rests on two simple
      principles: (a) all behavior constitutes choice; and (b) all activities take
      time. Equivalence between choice and behavior occurs because every situation
      contains more than one alternative activity. The principle that behavior takes
      time refers not simply to any notion of response duration, but to the necessity
      that identifying one action or another requires a sample extended in time. The
      molecular paradigm's momentary responses are inferred from extended samples in
      retrospect. In this sense, momentary responses constitute abstractions, whereas
      extended activities constitute concrete particulars. Explanations conceived
      within the molecular paradigm invariably involve hypothetical constructs, because
      they require causes to be contiguous with responses. Explanations conceived
      within the molar paradigm retain direct contact with observable variables.

PMID- 15157982
TI  - SQAB 2003. Proceedings of the meeting of the Society for the Quantitative
      Analyses of Behavior. May 23-24, 2003, San Francisco, California, USA.

PMID- 15157984
TI  - C-fos regulates neuropeptide Y expression in mouse dentate gyrus.
AB  - Excitotoxicity by which excitatory amino acid induces neuronal cell death may
      underlie mechanisms of neurodegenerative diseases. We previously found that c-fos
      is critically involved in neuronal excitability and survival. Mice that carry
      hippocampal mutations of c-fos exhibited hyper-excitability, hyper-excitotoxicity
      and higher mortality in kainic acid (KA)-induced seizures compared to wild-type
      mice. To further understand the neuroprotective signal transduction pathways
      regulated by c-fos in the hippocampal formation, we identified 172 genes that are
      either regulated by KA or are differentially expressed in wild-type and
      hippocampal-specific c-fos mutant mice using cDNA microarrays. One gene encodes
      the neuropeptide Y (NPY). We confirmed that c-fos regulates the expression of NPY
      by using immunohistochemistry. We found that c-fos is critical in up-regulation
      of NPY expression in the granule cell layer of dentate gyrus in response to KA
      administration. As NPY is an important endogenous anti-epileptic agent, our
      result is consistent with a hypothesis that the neuroprotective function of c-fos
      is mediated in part by regulation of NPY expression.

PMID- 15157983
TI  - Cannabinoids enhance N-methyl-D-aspartate-induced excitation of locus coeruleus
      neurons by CB1 receptors in rat brain slices.
AB  - We studied the effect of cannabinoids on the activity of N-methyl-d-aspartate
      (NMDA) receptors in the locus coeruleus from rat brain slices by single-unit
      extracellular recordings. As expected, NMDA (100 microM) strongly excited (by
      nine fold) the cell firing activity of the locus coeruleus. Perfusion with the
      endocannabinoid anandamide (1 and 10 microM) or the anandamide transport
      inhibitor AM 404 (30 microM) enhanced the NMDA-induced excitation of locus
      coeruleus neurons. Similarly, the synthetic agonists R(+)-WIN 55212-2 (10 microM)
      and CP 55940 (30 microM) enhanced the effect of NMDA. In the presence of the
      CB(1) receptor antagonists SR 141716A (1 microM) or AM 251 (1 microM), the
      enhancement induced by anandamide (10 microM) was blocked. Our results suggest
      that cannabinoids modulate the activity of NMDA receptors in the locus coeruleus
      through CB(1) receptors.

PMID- 15157985
TI  - Chronic administration of 2-(2-benzofuranyl)-2-imidazoline (2-BFI) induces region
      specific increases in [3H]2-BFI binding to rat central imidazoline I2 sites.
AB  - Chronic administration of I(2) ligands increases the density of central I(2)
      sites as measured in brain homogenates. Here, we have used autoradiography to
      examine whether the increase in I(2) site density induced by chronic
      administration of 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is uniform across
      brain regions. We dosed rats with 2-BFI 7 mg/kg or with saline vehicle i.p. over
      96 days. Compared with vehicle-treated rats, this treatment significantly
      increased specific [(3)H]2-BFI binding only in the arcuate nucleus and area
      postrema, by 63% and 67% respectively. There were no significant effects in the
      pineal gland or interpeduncular nucleus which, like the arcuate nucleus and area
      postrema, are rich in I(2) sites. These data indicate that chronic administration
      of 2-BFI selectively alters radioligand binding in two I(2) rich brain ideas,
      namely the arcuate nucleus and area postrema, suggesting there may be more than
      one population of I(2) sites in the rat brain.

PMID- 15157986
TI  - Tau protein in cerebrospinal fluid: a possible marker of poor outcome in patients
      with early relapsing-remitting multiple sclerosis.
AB  - We analyzed the prognostic value of Tau protein, a marker of axonal damage,
      detected in the cerebrospinal fluid (CSF) of patients with relapsing-remitting
      multiple sclerosis (RRMS). We sampled the CSF from 32 patients with probable or
      definite RRMS, having had the disease for less than 5 years. We studied the
      relationship between Tau protein concentration in the CSF (CSF-TAU) and
      disability, time to next relapse and time to experience a one point increase on
      the Expanded Disability Status Scale (EDSS). CSF-TAU was correlated with the
      Progression Index at the end of follow-up. Patients with higher CSF-TAU
      experienced a more rapid one point increase in the EDSS. CSF-TAU was the only
      independent variable to predict the time to next relapse. CSF-TAU, as a marker of
      axonal loss, may help us to predict short-term outcome in patients with early
      RRMS.

PMID- 15157987
TI  - Is there interaction between vision and local fatigue of the lower limbs on
      postural control and postural stability in human posture?
AB  - An investigation of the interaction between local fatigue and vision on postural
      control and postural stability was carried out. Fatigue was effected in a sitting
      position and was assumed based on a shortening of the exertion time of the soleus
      muscles (60% of their maximal voluntary contractions). Postural stability was
      assessed by centre of gravity motion, which was computed from centre of pressure
      motion, evaluating postural control. Ten healthy male subjects were asked to
      stand as still as possible with eyes open (EO) and eyes closed (EC) before and
      after the fatigue protocol. Results showed that fatigue produced similar effects
      for the two vision conditions on postural control and postural stability analyzed
      separately, increasing postural control and leaving postural stability unchanged.
      Local fatigue essentially produced an increase of neuromuscular activity in high
      frequencies. However, this increase was more pronounced for the EO, as compared
      to the EC condition.

PMID- 15157988
TI  - Density, but not shape, of hippocampal dendritic spines varies after a seizure
      inducing acute dose of monosodium glutamate in rats.
AB  - Dendritic spines are the main postsynaptic neuronal targets of excitatory inputs
      in cortical neurons, and both spine density and shape possess a well known
      adaptive synaptic-stimulation-dependent plastic capacity. Eighteen Sprague-Dawley
      adult male rats were used. Monosodium glutamate-treated rats (4 g/kg of body
      weight, i.p.) showed tonic and clonic epileptic seizures, as well as less
      dendritic spines in the apical arborization of their hippocampal CA1 pyramidal
      cells, compared to both control groups. No changes were seen in the proportional
      density of thin, stubby, mushroom-shaped, wide, or ramified spines between
      groups. Excessive glutamate-mediated excitatory activity on receptors could have
      led dendritic spines to shrink until they disappeared, while the spine-type
      proportion may be kept balanced as an adaptive response.

PMID- 15157989
TI  - Non-selective opioid receptor antagonism of the antidepressant-like effect of
      venlafaxine in the forced swimming test in mice.
AB  - The opioid system has been implicated in mood disorders as well as in the
      mechanism of action of antidepressants. Since the opioid component in venlafaxine
      (VLX) is still a matter of discussion, we investigated the role of opioid
      receptors in the antidepressant-like effect of VLX in the forced swimming test in
      mice. The non-selective opiate antagonist naloxone at high dose (2 mg/kg, s.c.)
      antagonized the effect of VLX. In contrast, beta-funaltrexamine (40 mg/kg, s.c.),
      which preferentially blocks mu(1)/mu(2) opioid receptors, naloxonazine (35 mg/kg,
      s.c.), a selective mu(1) opioid antagonist, naltrindole (10 mg/kg, s.c.), a
      selective delta opioid antagonist, and Nor-binaltorphimine (10 mg/kg, s.c.),
      which selectively blocks kappa-opioid receptors, were all ineffective. Thus,
      although apparently mediated by the opioid system, the behavioural effect of VLX
      does not involve specific opioid receptors.

PMID- 15157990
TI  - Chronic nicotine and smoking treatment increases dopamine transporter mRNA
      expression in the rat midbrain.
AB  - Previous pharmacokinetics and electrophysiological results indicated an important
      role of nicotine in the modulation of dopamine transporter (DAT). To elucidate
      the expression changes of DAT on chronic nicotine and smoke administration, the
      effects of nicotine and passive cigarette smoke on DAT mRNA expression in the
      ventral tegmental area (VTA) and the substantia nigra (SN) area were examined
      using in situ hybridization and RNase protection assay. The results showed that
      chronic nicotine and smoke exposure highly unregulated DAT mRNA in the VTA and SN
      areas, including the dorsal part of substantia nigra pars compacta. Smoke for 30
      min showed the highest increasing effect, whereas nicotine and smoke for 10 min
      only had slightly increasing effects. However, smoke for 1 h showed an increasing
      effect to a lesser extent than 30 min. These results revealed a new aspect of
      nicotine's modulation on the DAT, and may have important roles in
      neuropsychological disorders related to the midbrain abnormalities such as drugs
      addiction.

PMID- 15157991
TI  - Isolation and transplantation of dopaminergic neurons generated from mouse
      embryonic stem cells.
AB  - Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when
      co-cultured with PA6 stromal cells, but the resulting cultures contain a variety
      of unidentified cells. In order to label live DA neurons in mixed populations, we
      introduced a GFP reporter under the control of the tyrosine hydroxylase (TH) gene
      promoter into ES cells. GFP expression was observed in TH-immunoreactive cells
      that differentiated from the ES cells that carried the TH-GFP reporter gene. DA
      neurons expressing GFP were sorted from the mixed cell population by fluorescence
      activated cell sorting of cells exhibiting GFP fluorescence, and the sorted
      GFP(+) cells obtained were transplanted into a rat model of Parkinson's disease.
      Some of these cells survived and innervated the host striatum, resulting in a
      partial recovery from parkinsonian behavioral defects. This strategy of isolation
      and transplantation of ES-cell-derived DA neurons should be useful for cellular
      and molecular studies of DA neurons and for clinical application in the treatment
      of Parkinson's disease.

PMID- 15157992
TI  - The angiotensin I converting enzyme insertion/deletion polymorphism influences
      therapeutic outcome in major depressed women, but not in men.
AB  - Angiotensin converting enzyme (ACE) is expressed in the central nervous system
      (CNS), where its primary function comprises degradation of neuropeptides
      including substance P (SP). Because of the possible antidepressant effects of SP
      antagonists, the influence of SP on both pathophysiology and mitigation of
      depression has been hypothesized. It was shown that ACE plasma concentration is
      determined by an insertion/deletion (I/D) polymorphism represented by the
      presence or absence of a 287 bp DNA fragment within the ACE gene. Because the D
      allele was associated with higher ACE levels this may have a positive impact on
      the therapeutic efficacy of antidepressant treatment. Thus, variations in CNS
      expression of ACE might influence the response to various antidepressant
      therapies. We could show a divergent clinical outcome in relation to different
      genotypes in 313 depressed patients who were treated with various
      antidepressants. A lower HAM-D17 score after 4 weeks of treatment in D/D and I/D
      in comparison to I/I genotypes was detected; the duration of hospitalization was
      shorter in D allele carriers. The D allele seems to be a predictor for a faster
      onset of different antidepressant therapies. The patients' gender influences
      these outcome effects significantly. After subdivision of the patients according
      to their gender only female patients contributed significantly to the genotype
      dependent therapeutic outcome. Our investigation gives the first hint that the
      speed of onset of antidepressant therapies may be dependent on both variants of
      the ACE genes and the gender of the patients.

PMID- 15157993
TI  - The timecourse of induction of brain-derived neurotrophic factor mRNA and protein
      in the rat hippocampus following voluntary exercise.
AB  - In this study we examined the timecourse of induction of brain-derived
      neurotrophic factor (BDNF) mRNA and protein after 1, 3, 5, 7, 14 and 28 days of
      exercise in the rat. To measure the expression of mRNA for individual BDNF exons
      we utilized a semi-quantitative RT-PCR technique, while BDNF protein was assessed
      using commercial ELISA kits. We demonstrated that the distance run by animals
      increased significantly (P<0.05) after 4 weeks. BDNF protein was significantly
      (P<0.05) increased after 4 weeks of exercise, while the mRNA for individual BDNF
      exons increased significantly (P<0.05) over the timecourse (exon I after 1 and 28
      days and exons II and V after 28 days). The Morris water maze was then utilized
      to demonstrate that 3 weeks of prior exercise enhanced the rate of learning on
      this task. Exercise, therefore, was shown to modulate BDNF induction in a time
      dependent manner, and this may translate to improvements in neurotrophin-mediated
      tasks within the CNS.

PMID- 15157994
TI  - Lack of association between Alzheimer's disease and the promoter region
      polymorphisms of the nicastrin gene.
AB  - The biological analysis of nicastrin (NCSTN) shows its crucial role in gamma
      cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated
      altered gamma-cleavage activity, suggesting its potential implication in
      Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found
      two promoter single nucleotide polymorphisms (SNPs) at putative transcription
      binding sites, -796T/G and -1216C/A. The association study using the promoter
      SNPs showed no significant genetic effect upon the development of AD. Haplotype
      analysis with the promoter SNPs and coding SNPs demonstrated no significant
      difference between familial AD cases and controls. Moreover, the genotype of each
      promoter SNP did not have an association with age-at-onset in AD. Our
      investigation suggests that the two promoter SNPs are unrelated to the
      development of AD, however, further investigation at the promoter region of NCSTN
      may be necessary to address its potential implication of gene expression in AD.

PMID- 15157995
TI  - Endothelial nitric oxide synthase phosphorylated at Ser116 is localized in nerve
      fibers of the rat glandulae palatinae.
AB  - It is known that total endothelial nitric oxide synthase (eNOS) is localized in
      peripheral nerve fibers, but the existence of the phosphorylation site/s of eNOS
      in peripheral nerve fibers is unknown. In the perfusion-fixed and decalcified
      sections of rat palates, eNOS and eNOS phosphorylated at Ser(116) were identified
      in the nerve fibers of the glandulae palatinae. The localization of eNOS
      phosphorylated at Ser(1177) and Thr(495) in nerve fibers was undetectable. It is
      concluded that eNOS is phosphorylated at Ser(116) in nerve fibers of the
      glandulae palatinae under basal conditions. The basal Ser(1177) and Thr(495)
      phosphorylation of eNOS are missing in nerve fibers of the glandulae palatinae.

PMID- 15157996
TI  - Neuroprotective effect of gamma-glutamylethylamide (theanine) on cerebral
      infarction in mice.
AB  - In the present study, we examined the neuroprotective effect of gamma
      glutamylethylamide (theanine) on the ischemic brain damage in a middle cerebral
      artery occlusion model in mice. Theanine was injected i.p. 3 h after the
      occlusion or immediately before and 3 h after the occlusion. Theanine (1 mg/kg)
      significantly decreased the size of the cerebral infarcts 1 day after the
      occlusion. In contrast, theanine did not affect the cerebral blood flow, brain
      temperature and physiological variables (pH, pCO(2), pO(2) and hematocrit) in
      this model. These results suggest that theanine directly provides neuroprotection
      against focal cerebral ischemia and may be clinically useful for preventing
      cerebral infarction.

PMID- 15157997
TI  - Proton magnetic resonance spectroscopy in children with spastic diplegia.
AB  - The objective of this prospective study was the application of proton magnetic
      resonance spectroscopy in children with spastic diplegia (SD) to determine the
      metabolite profile of SD children in the left basal ganglia, and to assess the
      relationship of this profile with motor and mental development. Patients with SD
      showed reduced ratios of N-acetylaspartate (NAA)/creatine (Cr), NAA/choline
      (Cho), NAA/myo-inositol (mI), Cho/NAA, Cho/Cr and Cho/mI in the basal ganglia
      compared to a well-matched control group. On the other hand, we noted increased
      Cr/NAA, Cr/Cho and mI/NAA ratios in the SD patients as compared with controls.
      NAA/mI ratios were positively correlated with the severity scale of cerebral
      palsy in SD children. There was also a significant correlation between Cr/NAA and
      mental retardation. Increased Cr/NAA, Cr/Cho and mI/NAA ratios in SD children may
      suggest the existence of the compensatory mechanisms in these patients. The
      NAA/mI ratio could be used as an additional marker of SD severity and Cr/NAA as a
      marker of the mental retardation.

PMID- 15157998
TI  - Abnormal left superior temporal gyrus volumes in children and adolescents with
      bipolar disorder: a magnetic resonance imaging study.
AB  - Abnormalities in left superior temporal gyrus (STG) have been reported in adult
      bipolar patients. However, it is not known whether such abnormalities are already
      present early in the course of this illness. Magnetic resonance imaging (MRI)
      morphometric analysis of STG was performed in 16 DSM-IV children and adolescents
      with bipolar disorder (mean age+/-SD 15.5+/-3.4 years) and 21 healthy controls
      (mean age+/-SD 16.9+/-3.8 years). Subjects underwent a 3D spoiled gradient
      recalled acquisition MRI examination. Using analysis of covariance with age,
      gender and intra-cranial brain volume as covariates, we found significantly
      smaller left total STG volumes in bipolar patients (12.5+/-1.5 cm(3)) compared
      with healthy controls (13.6+/-2.5 cm(3)) (F=4.45, d.f.=1, 32, P=0.04). This
      difference was accounted for by significantly smaller left and right STG white
      matter volumes in bipolar patients. Decreased white matter connections may be the
      core of abnormalities in STG, which is an important region for speech, language
      and communication, and could possibly underlie neurocognitive deficits present in
      bipolar patients.

PMID- 15158000
TI  - Ultrastructural characteristics of circadian pacemaker neurones, immunoreactive
      to an antibody against a pigment-dispersing hormone in the fly's brain.
AB  - Neurones immunoreactive to an antibody against a pigment-dispersing hormone (PDH
      ir) are considered to be pacemaker cells in the neuronal circadian system of
      flies. We investigated the ultrastructure of PDH-ir varicosities, possible
      releasing sites of the PDH-like peptide, in the distal medulla of the optic lobe
      and in the dorsal protocerebrum of the two fly species Drosophila melanogaster
      and Musca domestica. In both species PDH-ir varicosities show accumulation of
      dense core vesicles (DCVs). PDH-like peptide is localized in the DCVs as shown by
      post-embedding immuno-electron microscopy. Localization of PDH-like peptide in
      DCVs and normally lacking synaptic specializations at PDH-ir varicosities in the
      medulla are interpreted as a non-synaptic paracrine release of peptide.

PMID- 15157999
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits cell proliferation through
      arylhydrocarbon receptor-mediated G1 arrest in SK-N-SH human neuronal cells.
AB  - The neurotoxic mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has not
      been completely elucidated. In this study we investigated the possible role of
      cell cycle regulators and their dependence on arylhydrocarbon receptor (AhR) in
      the TCDD-mediated inhibition of cell proliferation using a human neuronal cell
      system. TCDD suppressed DNA synthesis of SK-N-SH human neuronal cells determined
      by [(3)H]thymidine incorporation which was significantly prevented either by
      pretreatment with alpha-naphthoflavone (alpha-NF), a partial AhR antagonist, or 8
      methoxypsoralen (MOP), a binding inhibitor of activated AhR to dioxin response
      elements. Cell cycle analysis showed that TCDD induced a G(1) cell cycle arrest,
      which was also significantly prevented by pretreatment with alpha-NF and MOP.
      TCDD did not alter the expression of cyclin D, cyclin E, p21 and p53. However,
      TCDD induced an enhanced expression of p27 and a hypophosphorylation of pRb,
      which was prevented by alpha-NF and MOP. Combined, these results suggest that the
      TCDD-induced inhibition of neuronal cell proliferation may be due to the AhR
      dependent G(1) arrest through an enhanced expression of p27 and a
      hypophosphorylation of pRB.

PMID- 15158001
TI  - Analysis of polymorphisms at the tumor suppressor gene p53 (TP53) in contributing
      to the risk for schizophrenia and its associated neurocognitive deficits.
AB  - Owing to the role of the nuclear phosphoprotein p53 in the regulation of
      neurodegeneration and neurodevelopmental processes, some authors have suggested
      TP53 as a candidate gene for schizophrenia and/or the neurocognitive deficits
      commonly observed in these patients. In the present study we have analyzed two
      polymorphisms (Pro72Arg and 16 bp insertion) located on the TP53 gene in order to
      investigate their role in the risk of developing schizophrenia and their effect
      on the neurocognitive profile of these patients in the context of an association
      study. The distribution of genotypes, alleles and haplotypes did not differ
      between cases and controls. Additionally, we did not detect any influence of this
      genetic variability in the neurocognitive functions of schizophrenic patients.
      Our findings suggest that the analyzed variability of the TP53 gene does not
      influence (i) the risk of suffering from schizophrenia and (ii) the deficits in
      the neurocognitive profile of these patients.

PMID- 15158002
TI  - Lack of association between angiotensin I-converting enzyme insertion/deletion
      gene functional polymorphism and panic disorder in humans.
AB  - Family and twin studies have indicated that genes influence susceptibility to
      panic disorder, but the genes involved remain unknown. The neuropeptide
      angiotensin II has been found to be involved in anxiety and regulation of
      respiration which are important in the pathophysiology of panic attacks. Assuming
      that angiotensins may be candidate genes in panic disorder, we analyzed the
      association between panic disorder and angiotensin I-converting enzyme (ACE)
      insertion (I)/deletion (D) gene functional polymorphism. We recruited 101
      patients with panic disorder diagnosed according to DSM-IV criteria, and 184
      control subjects in the study. No significant differences in the frequency of the
      genotype or allele in the polymorphism between patient and control groups were
      found (genotype, chi(2)=0.56, d.f.=2, P=0.77; allele, chi(2)=0.074, d.f.=1,
      P=0.78). This study suggests that the ACE I/D gene polymorphism is not directly
      associated with panic disorder in our Japanese patient group.

PMID- 15158003
TI  - Suprasegmental speech cues are automatically processed by the human brain: a
      mismatch negativity study.
AB  - This study investigates the electrical brain activity correlates of the automatic
      detection of suprasegmental and local speech cues by using a passive oddball
      paradigm, in which the standard Hungarian word 'banan' ('banana' in English) was
      contrasted with two deviants: a voiceless phoneme deviant ('panan'), and a stress
      deviant, where the stress was on the second syllable, instead of the obligatory
      first one. As a result, we obtained the mismatch negativity component (MMN) of
      event-related brain potentials in each condition. The stress deviant elicited two
      MMNs: one as a response to the lack of stress as compared to the standard
      stimulus, and another to the additional stress. Our results support that the MMN
      is as valuable in investigating processing characteristics of suprasegmental
      features as in that of phonemic features. MMN data may provide further insight
      into pre-attentive processes contributing to spoken word recognition.

PMID- 15158004
TI  - Very slow potential oscillations in locus coeruleus and dorsal raphe nucleus
      under different illumination in freely moving rats.
AB  - Recent findings have revealed very slow (<0.5 Hz) oscillatory phenomena in the
      structures of the brain visual system. It has been proposed that very slow brain
      potentials in an extremely slow domain, less than 0.1 Hz, recorded from the
      lateral geniculate complex and primary visual cortex are associated with periodic
      influences originating from the locus coeruleus and dorsal raphe nucleus. The
      present study was performed to test the hypothesis that extremely slow brain
      potential oscillatory patterns in the locus coeruleus and dorsal raphe nucleus
      during several types of visual stimulation--light exposure, darkness, and
      photostimulation--are similar to those in the primary visual cortex and lateral
      geniculate complex under the same conditions of illumination. The results support
      this hypothesis. Specifically, spectral patterns of multisecond oscillations in
      the range of 0.02-0.04 Hz and fluctuations in the domain of minutes (below 0.002
      Hz) were present in both the locus coeruleus and dorsal raphe nucleus and were
      similar to those found in the primary visual cortex and lateral geniculate
      complex. Additionally, we detected significant increases in the power spectra of
      multisecond oscillations in both nuclei in response to photostimulation (P<0.05).
      Our tentative conclusion is that extremely slow potentials in the locus coeruleus
      and dorsal raphe nucleus contribute to the regulation of extremely slow activity
      in the brain visual system.

PMID- 15158005
TI  - Telomerase induction in astrocytes of Sprague-Dawley rat after ischemic brain
      injury.
AB  - Telomerase, a reverse transcriptase, consists of an RNA template and protein
      polymerase. This ribonucleoprotein protects the linearized chromosomal end region
      and elongates the telomere during chromosomal replication. Telomerase is not
      expressed in adult somatic cells but it shows high activity in most cells during
      embryonic development. We report, by RT-PCR and immunohistochemical results, that
      the induction of telomerase protein catalytic subunit (TERT) in transient middle
      cerebral artery occlusion induced brain injury. TERT mRNA emerged 24 h after
      ischemia. We examined which brain cell expressed TERT in the penumbra region of
      injured brain. The expression of TERT began from 24 h and remained until 5 days
      after ischemia. We identified that TERT was co-localized with the astrocyte
      marker, GFAP, at 3 days after ischemia. This is strong evidence that TERT is
      induced in astrocytes when the brain is damaged by ischemia, and that this enzyme
      may play an important role in ischemic brain injury.

PMID- 15158006
TI  - Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's
      disease: a 1H magnetic resonance spectroscopy study.
AB  - We quantified the differential effects of the spin-spin relaxation times (T2) of
      tissue water and cerebral spinal fluid in order to examine hippocampal T2 changes
      as a non-invasive bio-marker of Alzheimer's disease (AD). We measured T2 in the
      right hippocampus of ten patients fulfilling the NINCDS-ADRDA criteria for AD and
      40 healthy adult volunteers using localized proton magnetic resonance
      spectroscopy. The T2 values of AD patients (73 +/- 8 ms) were significantly
      shorter (P < 0.01) than those of healthy age-matched controls (81 +/- 5 ms), and
      there was a reduction in T2 for healthy older vs. healthy younger adults (87 +/-
      5 ms, P < 0.05). The reduced T2 values with aging are consistent with age-related
      decreases in tissue water content. Our results suggest that there may be a severe
      reduction in tissue water content in AD.

PMID- 15158007
TI  - A single pulmonary mechano-sensory unit possesses multiple encoders in rabbits.
AB  - Morphological studies have shown that axons of slowly adapting pulmonary stretch
      receptors (SARs) may supply more than one receptor structure. Thus, a single-unit
      of SARs may contain multiple encoders. We recorded SAR activities and searched
      for multiple receptive fields (MRFs) by probing the lung in anesthetized, open
      chest and mechanically ventilated rabbits. One-third of SARs had clear MRFs.
      Selectively blocking fields with lidocaine, we found that each has its own
      encoder and discharge characteristics. Unit activity of SARs results from encoder
      interactions and undergoes significant integration before reaching the central
      nervous system.

PMID- 15158008
TI  - The human pulvinar and attentional processing of visual distractors.
AB  - The processing of a target is degraded when noise is present in proximity, and
      performance increases as the target-noise distance increases. We tested a group
      of healthy volunteers and a group of patients, who suffered strokes in the
      posterior thalamus, in a task where the target-noise distance was manipulated.
      Whilst controls exhibited the expected pattern of results, thalamic patients
      exhibited little signs of noise interference. Interference occurred when the
      target-noise distance was 0 degrees (the target and noise were superimposed), but
      it was absent for distances equal to and bigger than 1 degree. The results
      suggest that the coarse grain of visual attention reported previously might be
      due to some aspects of attention processing underlain by the pulvinar and acting
      to grab the visual context or background of a target.

PMID- 15158009
TI  - Pharmacological but not physiological concentrations of melatonin reduce iron
      induced neuronal death in rat cerebral cortex.
AB  - Iron-mediated oxidative stress occurs in a wide variety of neurological
      disorders. The present study has investigated whether melatonin can alter the
      proportion of neurons that die in the 24 h period following 1.0 microl
      intracortical injections of 1.0 mM ferric ammonium citrate (FAC) or 0.9% saline.
      Rats which received systemic infusions of melatonin (5 mg/kg body weight per day)
      displayed a 40% reduction (P = 0.019) in the proportion of neurons killed by FAC.
      By contrast, reduction of endogenous melatonin by continuous light exposure did
      not significantly affect the extent of neuronal death. Furthermore, elevated or
      reduced melatonin levels did not alter the number of neurons killed by saline
      injections. We conclude that pharmacological concentrations of melatonin protect
      neurons against iron-induced injury.

PMID- 15158010
TI  - Alterations in monoamine levels after cocaine-induced status epilepticus and
      death in striatum and prefrontal cortex of mice.
AB  - Seizures and death are the more important toxic consequences related to cocaine
      overdose. Some reports have shown that pharmacological manipulations in
      dopaminergic, serotonergic and noradrenergic systems alter the occurrence of
      cocaine-induced convulsions and death. Based on this fact, this work was
      performed to determine the changes in monoamine levels (DA, 5-HT and NE) and
      their metabolites (DOPAC, HVA and 5-HIAA) after cocaine-induced status
      epilepticus (SE) and death in striatum and prefrontal cortex (PFC). The
      monoamines and their metabolites were assayed by reverse-phase high-performance
      liquid chromatography with electrochemical detection. Animal SE in striatum
      presented a decrease in DA and NE levels and an increase in HVA although in PFC
      there was an increase in DA, 5-HT and NE. Animals that died from cocaine-induced
      seizures in striatum showed an increase only in NE levels, but on the other hand
      in PFC a decrease occurred in DA and NE levels. Taken together these results
      indicated that cocaine-induced SE and death altered monoamine levels in different
      ways depending on the brain area studied, suggesting that different mechanisms
      are involved.

PMID- 15158011
TI  - Serotonin transporter polymorphism related to amygdala excitability and symptom
      severity in patients with social phobia.
AB  - A functional polymorphism in the promoter region of the human serotonin
      transporter (5-HTT) gene has been related to negative affect and amygdala
      activity. We studied amygdala activation during social anxiety provocation in
      relation to affective ratings and 5-HTT genetic variation. [H2(15)O]positron
      emission tomography was used to estimate amygdala blood flow during private and
      public speaking (baseline and anxiety conditions) in 17 patients with social
      phobia. Genotyping identified patients with long and short alleles in the
      promoter region of the 5-HTT. Individuals with one or two copies of the short
      allele exhibited significantly increased levels of anxiety-related traits, state
      anxiety, and enhanced right amygdala responding to anxiety provocation, compared
      with subjects homozygous for the long allele. Thus, 5-HTT genetic variation was
      associated with symptom severity and amygdala excitability in social phobia.

PMID- 15158012
TI  - Gender differences in hemispheric organization during divergent thinking: an EEG
      investigation in human subjects.
AB  - This study examined the gender-related differences in EEG patterns during the
      experimental condition of divergent thinking. The EEG of 36 males and 27 females
      was recorded from 16 scalp electrodes in rest and while students were solving a
      creative problem. The spectral power density along with EEG coherence estimates
      were analyzed in each of the six frequency bands in the 4-30 Hz range. Gender
      related differences in the EEG patterns were found during successful divergent
      thinking. Creative men were characterized by massive increases of amplitude and
      interhemispheric coherence in the beta2 whereas creative women showed more local
      increases of the beta2 power and coherence. On the contrary, the task-induced
      desynchronization of the alpha1 rhythm in creative women was topographically more
      expanded as compared with men who demonstrated greater interhemispheric coherence
      than women did. Our results propose a different hemispheric organization in men
      and women during creative thinking.

PMID- 15158013
TI  - Essential components for a glutamatergic synapse between Merkel cell and nerve
      terminal in rats.
AB  - The exact role of Merkel cells and their possible involvement in mechanosensation
      is unclear. The aim of this study was to determine, in the adult rat sinus hair
      follicle, the expression pattern of a number of vesicular proteins involved in
      neurotransmitter release to provide a clearer understanding of Merkel cell
      signalling mechanisms. We identified prominent expression and co-localization of
      the glutamatergic vesicle loading proteins VGLUT1 and VGLUT2 at the site of the
      sinus hair follicle known to be densely populated with Merkel cells. We also
      found expression of the vesicle recycling proteins synaptogyrin and syntaxin-6 in
      the same region of the hair follicle. Our data suggest that glutamate signalling
      is involved in Merkel cell mechanosensation and that vesicular trafficking is
      commonplace in the Merkel cell-neurite complex.

PMID- 15158014
TI  - Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve
      regeneration.
AB  - Bone marrow mesenchymal stem cells can trans-differentiate into neuronal
      phenotypes. We examined the differentiation of marrow stromal cells (MSCs) in
      culture and during nerve regeneration. MSCs from adult rats were exposed to glial
      growth factor (GGF) to stimulate glial differentiation. Subsequently
      differentiated MSCs were retrovirally labelled with green fluorescent protein and
      transplanted into 1 cm nerve conduits in the rat sciatic nerve. Fifteen days post
      operatively the conduits were examined for axonal and Schwann cell regeneration
      and MSC integration. In vitro, MSCs exposed to GGF expressed S100 and glial
      fibrillary acidic protein. Following transplantation, MSCs maintained S100
      expression and enhanced nerve regeneration, with significant Schwann cell
      regeneration compared to control (2.7 +/- 0.21 vs. 2.05 +/- .21 mm; P < 0.05).
      MSCs not exposed to GGF prior to transplantation expressed S100 in vivo
      indicating glial differentiation in response to local cytokines and growth
      factors.

PMID- 15158015
TI  - Mismatch negativity to frequency changes: no evidence from human event-related
      brain potentials for categorical speech processing of complex tones resembling
      vowel formant structure.
AB  - Based on a memory-comparison process, changes in the pitch of repetitive sounds
      are pre-attentively detected, reflected by the mismatch negativity (MMN) event
      related brain potential. In the present investigation of categorical speech
      perception, complex tones were used that consisted of vowel-defining F1 and F2
      formant information while not being perceived as speech. MMN was obtained in
      oddball blocks. The auditory system tracks two simultaneous changes in formant
      frequencies of 50 Hz while also abstracting from three levels of intensity
      variation. Lower frequency deviants elicited larger MMN. No effects of language
      categorical processing were observed.

PMID- 15158016
TI  - Putrescine as a marker of the effects of 2-chloropropionic acid in the rat brain.
AB  - The neurotoxin 2-chloropropionic acid (2CPA, 750 mg/kg, per os) induces ataxia in
      rats causing neuropathological changes (necrosis and edema) localized mainly in
      the cerebellum (CB). It has been described that putrescine (PUT) is a good marker
      of severe brain damage. We measured the concentration of PUT (by HPLC) in ataxic
      rat brains 3 days after 2CPA dosing. PUT was 9-fold higher than normal values in
      CB, 5-fold higher in midbrain (MB) and medulla oblongata + pons (MO) and 3-fold
      higher in the remaining areas studied. Treatment with glycerol, a reducer of
      brain edema, lowered the concentration of PUT only in CB, MB and MO. Histological
      damage was found in CB and the spinal trigeminal nucleus (located in the
      pontomedullar brainstem). We suggest that PUT can act as a marker of both
      neuronal necrosis and brain edema.

PMID- 15158017
TI  - Cholecystokinin and prostaglandins inhibit responses of vagal afferent activity
      to systemic administration of nicotine in anesthetized rats.
AB  - Systemic administration of nicotine suppresses food intake. Since gastric vagal
      afferents convey satiation signals to the hypothalamus in response to
      cholecystokinin, we investigated the possibility that nicotine increases afferent
      activity of the gastric vagal nerves by stimulating release of cholecystokinin.
      Furthermore, involvement of prostaglandins in the responses of gastric vagal
      afferents to nicotine was also investigated because prostaglandins stimulate
      gastric vagal afferent activity. Experiments were performed in urethane
      anesthetized rats. Intravenous administration of 300 microg/kg but not 3 or 30
      microg/kg nicotine produced biphasic increases in afferent activity. The maximum
      of the first increase was reached within 1 min, while that of the second increase
      was reached 10-15 min after nicotine injection. Pretreatment with MK-329, a type
      A cholecystokinin receptor antagonist, significantly reduced the first increase,
      without influencing the second increase. Pretreatment with indomethacin, a
      cyclooxygenase inhibitor, further reduced the first increase and abolished the
      second increase. These results suggest that nicotine can exert its anorexic
      effect via an increase in gastric vagal afferent activity which is caused by
      enhanced release of both cholecystokinin and prostaglandins.

PMID- 15158018
TI  - Ischemic preconditioning decreases intracellular zinc accumulation induced by
      oxygen-glucose deprivation in gerbil hippocampal CA1 neurons.
AB  - In normal gerbils, intracellular zinc ions ([Zn2+]i) and calcium ions ([Ca2+]i)
      accumulate in hippocampal CA1 neurons after global ischemia. We examined whether
      ischemic preconditioning modifies these changes in gerbil hippocampal slices. In
      normal slices, large increases in [Zn2+]i and [Ca2+]i were observed in the
      stratum radiatum of the CA1 area after oxygen-glucose deprivation. In
      preconditioned slices, there were significantly decreased peak levels of [Zn2+]i
      and [Ca2+]i in CA1. However, there were no differences in the peak levels of
      these ions in CA3 and dentate gyrus. These results suggest that modified [Zn2+]i
      and [Ca2+]i accumulation after an ischemic insult might be important for the
      mechanisms of ischemic tolerance induced by preconditioning.

PMID- 15158019
TI  - Chronic ethanol inhibits CXC chemokine ligand 10 production in human A172
      astroglia and astroglial-mediated leukocyte chemotaxis.
AB  - Astroglia are the most prevalent cell type in the human central nervous system
      (CNS) and perform important roles in normal tissue homeostasis, during
      pathological events and following trauma. Astroglial-derived chemokines have
      important neurotrophic effects and are important to CNS immunocompetence and
      response to injury, in part, due to their direct role in leukocyte and microglial
      cell recruitment. However, while ethanol is known to induce CNS pathologies and
      to be peripherally immunosuppressive, ethanol effects on chemokine expression in
      human astroglia are essentially unknown. We have demonstrated that chemotaxis of
      human U937 leukocytic cells, across a 0.5 microm pore polycarbonate transmembrane
      insert, is induced in response to culture media collected from 10 microg/ml
      lipopolysaccharide (LPS) + 10 ng/ml interleukin (IL)-1beta-stimulated A172 human
      astroglia cells. The involvement of the chemokine CXCL10 (also known as
      interferon-gamma inducible protein or IP-10) in astroglial-induced chemotaxis of
      U937 cells has been indicated, as chemotaxis can be reduced by an anti-CXCL10
      neutralizing antibody. Interestingly, chemotaxis of U937 cells, in response to
      astroglial-exposed media, is reduced when astroglia are chronically (9 days)
      exposed to 50 mM ethanol before stimulation with LPS + IL-1beta. Furthermore, we
      observed that LPS + IL-1beta-stimulated CXCL10 production is inhibited in human
      A172 astroglia exposed to chronic 50 mM ethanol. Thus, alterations in astroglial
      CXCL10 expression may disrupt CNS immunocompetence and play an important role in
      ethanol-induced CNS pathologies.

PMID- 15158020
TI  - Protective effects of S-nitrosoglutathione against neurotoxicity of 3
      nitropropionic acid in rat.
AB  - Mitochondrial dysfunction and oxidative stress are often linked to various
      neurodegenerative disorders including ischemic stroke and Huntington's disease
      (HD). S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier recently
      identified as a potent antioxidant capable of neutralizing oxidative stress. In
      the present study, we explore the neuroprotective effects of GSNO against
      metabolic insults induced by 3-nitropropionic acid (3-NP), a mitochondrial
      complex II inhibitor commonly used as a pharmacological model for HD, in primary
      culture of fetal rat cortical and striatal neurons. Application of GSNO (1-5
      microM) substantially reduced neuronal loss caused by 3-NP (1-5 mM) exposure
      based on MTT reduction, lactate dehydrogenase (LDH) release, and Hoechst staining
      assays. The protective effect of GSNO appeared to be more potent than N-acetyl-l
      cysteine (NAC), a glutathione precursor, at the same concentrations. These
      results suggest that manipulation of GSNO metabolism may exert protective effects
      against mitochondrial dysfunction often observed in neurodegenerative disorders.

PMID- 15158021
TI  - Locomotor recovery and mechanical hyperalgesia following spinal cord injury
      depend on age at time of injury in rat.
AB  - We tested the effect of age at the time of spinal cord injury (SCI) on locomotor
      recovery, in open field tests, and mechanical hyperalgesia, using paw withdrawal
      frequency (PWF) in response to noxious mechanical stimuli, in male Sprague-Dawley
      rats after spinal hemisection at T13 in young (40 days), adult (60 days) and
      middle-age (1 year) groups. Behavioral outcomes were measured weekly for 4 weeks
      in both SCI and sham groups. Following SCI, the young and adult groups recovered
      significantly more locomotor function, at a more rapid rate, than did the middle
      age group. The PWF of the young group was significantly increased, the adult
      group was significantly decreased, and the middle-age group showed no significant
      change in fore- and hindlimbs when compared to other age groups, pre-injury and
      sham controls. These results support age-dependent behavioral outcomes after SCI.

PMID- 15158022
TI  - Spinal pathways mediating coeruleospinal antinociception in the rat.
AB  - In a previous study, we showed in rats that axons of some locus
      coeruleus/subcoeruleus (LC/SC) neurons involved in coeruleospinal modulation of
      nociception descend through the ipsilateral side of the spinal cord and cross the
      midline at spinal segmental levels. The present study was designed to investigate
      a possible spinal pathway of these descending axons from the LC/SC. Extracellular
      recordings were made from the left dorsal horn with a carbon filament electrode
      (4-6 M(omega)). To block impulses from the LC/SC which descend through spinal
      pathways ipsilateral to the recording sites, a hemisection of the spinal cord
      ipsilateral to the recording sites was performed at the C2 level with fine
      forceps in all rats tested. In these rats, responses of dorsal horn neurons to
      noxious heat (53 degrees C) applied to receptive fields were inhibited during
      electrical stimulation (100 microA, 100 Hz, 0.1 ms pulses) of the LC/SC. The
      transection of the dorsolateral funiculus contralateral to the recording sites
      did not affect LC/SC stimulation-produced inhibition. Following transection of
      the ventrolateral funiculus (VLF) contralateral to the recording sites, LC/SC
      stimulation failed to inhibit heat-evoked responses. These results suggest that
      interruption of descending inhibition from the LC/SC produced by the VLF
      transections is due to the blockage of axons descending in the ventrolateral
      quadrant of the spinal cord, but not in the dorsolateral quadrant.

PMID- 15158023
TI  - The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression
      in the striatum of the rat.
AB  - Retigabine activates inward potassium rectifying KCNQ channels. This stabilizes
      the membrane potential via hyperpolarization in vitro and retigabine has also
      been shown to inhibit convulsions in vivo. This study was carried out to
      determine whether retigabine inhibited haloperidol-dependent activation of
      neurons in the striatum as measured by expression of c-Fos. Groups of male rats
      were treated with retigabine (10 mg/kg i.p.), haloperidol (1 mg/kg i.p.), or the
      two in combination (at 15 min interval) and fixed 60 min after haloperidol
      treatment. Haloperidol produced a large increase in the number of c-Fos-positive
      nuclei in different degrees in all parts of the striatum. Pretreatment with
      retigabine completely blocked haloperidol-induced c-Fos in both the ventral and
      dorsal striatum suggesting that retigabine via activation of the KCNQ channel
      interacts with haloperidol and inhibits neuronal excitation in the striatum.

PMID- 15158025
TI  - Synaptic stimulation of Aplysia peptidergic neurons can activate hormone
      secretion in the absence of an afterdischarge.
AB  - For over 20 years, the bag cell neurons of the marine mollusk Aplysia have been
      used to investigate second-messenger pathways that mediate effects of synaptic
      stimulation on ion currents and membrane excitability, presumably leading to
      exocytotic release of the neuropeptide egg-laying hormone (ELH). It is widely
      cited that a train of action potentials, called an afterdischarge, is necessary
      for activating cellular events leading to ELH secretion. Using a combination of
      electrophysiology, optical imaging of calcium signaling, and radioimmunoassay of
      ELH secretion, we show that an afterdischarge is not required for ELH secretion.
      Electrical stimulation that failed to produce afterdischarges but did lead to
      prolonged membrane depolarization and a rise in intracellular calcium
      concentration was sufficient to stimulate significant ELH release.

PMID- 15158024
TI  - Both 3,4-dihydroxyphenylalanine and dopamine releases are regulated by Ca2+
      induced Ca2+ releasing system in rat striatum.
AB  - To clarify the striatal Ca2+-dependent monoaminergic exocytosis mechanisms, this
      study determined the effects of the Ca2+-induced Ca2+ releasing system (CICR),
      containing inositol-trisphosphate-receptor (IP3R) and ryanodine-receptor (RyR),
      on striatal releases of dopamine and its precursor, 3,4-dihydroxyphenylalanine
      (DOPA), using microdialysis. The basal dopamine release is regulated by IP3R but
      not by RyR, whereas basal DOPA release does not require CICR. The K+-evoked
      releases of DOPA and dopamine were enhanced by IP3R agonist, whereas RyR agonist
      reduced it. Additionally, inhibition of dopamine release induced by RyR
      hyperactivation was prevented by inhibition of L-type voltage-sensitive Ca2+
      channel activity. These present results suggest that CICR-associated regulation
      of striatal releases of DOPA and dopamine is restrictive during the resting
      stage, whereas CICRs play an important role as a reserve mechanism of exocytosis
      of striatal DOPA and dopamine during the hyperexcitable stage.

PMID- 15158026
TI  - Glutamate-induced cell death of immortalized murine hippocampal neurons:
      neuroprotective activity of heme oxygenase-1, heat shock protein 70, and sodium
      selenite.
AB  - HT22 immortalized hippocampal neurons serve as a cellular model system to study
      oxidative stress, an imbalance of cellular redox homeostasis. Glutamate induces
      HT22 cell death by inhibiting the uptake of cystine into the cells via the
      cystine/glutamate transport system xc-, thus leading to reduced levels of
      glutathione. Here, we show that glutamate-induced cell death is attenuated in
      HT22 cells overexpressing heat shock protein 70 or heme oxygenase-1. Moreover,
      supplementing the culture medium with sodium selenite completely protected HT22
      against oxidative glutamate toxicity. In contrast, neither heat shock protein 70
      nor heme oxygenase-1 expression or increased concentrations of sodium selenite
      protected HT22 cells against serum withdrawal-induced cell death. These data
      indicate that glutamate-induced cell death differs substantially from that
      induced by growth factor deprivation.

PMID- 15158027
TI  - Folic acid in the monkey brain: an immunocytochemical study.
AB  - The present report describes the first visualization of folic acid-immunoreactive
      fibers in the mammalian central nervous system using a highly specific antiserum
      directed against this vitamin. The distribution of folic acid-immunoreactive
      structures was studied in the brainstem and thalamus of the monkey using an
      indirect immunoperoxidase technique. We observed fibers containing folic acid,
      but no folic acid-immunoreactive cell bodies were found. In the brainstem, no
      immunoreactive structures were visualized in the medulla oblongata, pons, or in
      the medial-caudal mesencephalon, since at this location immunoreactive fibers
      containing folic acid were only found at the rostral level in the dorsolateral
      mesencephalon (in the mesencephalic-diencephalic junction). In the thalamus, the
      distribution of folic acid-immunoreactive structures was more widespread. Thus,
      we found immunoreactive fibers in the midline, in nuclei close to the midline
      (dorsomedial nucleus, centrum medianum/parafascicular complex), in the ventral
      region of the thalamus (ventral posteroinferior nucleus, ventral posteromedial
      nucleus), in the ventrolateral thalamus (medial geniculate nucleus, lateral
      geniculate nucleus, inferior pulvinar nucleus) and in the dorsolateral thalamus
      (lateral posterior nucleus, pulvinar nucleus). The highest density of fibers
      containing folic acid was observed in the dorsolateral mesencephalon and in the
      pulvinar nucleus. The distribution of folic acid-immunoreactive structures in the
      monkey brain suggests that this vitamin could be involved in several mechanisms,
      such as visual, auditory, motor and somatosensorial functions.

PMID- 15158028
TI  - Morphology, chemistry and distribution of neoformed spherulites in agricultural
      land affected by metallurgical point-source pollution.
AB  - Metal distribution patterns in superficial soil horizons of agricultural land
      affected by metallurgical point-source pollution were studied using optical and
      electron microscopy, synchrotron radiation and spectroscopy analyses. The site is
      located in northern France, at the center of a former entry lane to a bunker of
      World War II, temporarily paved with coarse industrial waste fragments and
      removed at the end of the war. Thin sections made from undisturbed soil samples
      from A and B horizons were studied. Optical microscopy revealed the occurrence of
      yellow micrometer-sized (Ap horizon) and red decamicrometer-sized spherulites
      (AB, B(1)g horizons) as well as distinct distribution patterns. The chemical
      composition of the spherulites was dominated by Fe, Mn, Zn, Pb, Ca, and P.
      Comparison of calculated Zn stocks, both in the groundmass and in spherulites,
      showed a quasi-exclusive Zn accumulation in these neoformed features. Their
      formation was related to several factors: (i) liberation of metal elements due to
      weathering of waste products, (ii) Ca and P supply from fertilizing practices,
      (iii) co-precipitation of metal elements and Ca and P in a porous soil
      environment, after slow exudation of a supersaturated soil solution in more
      confined mineral media.

PMID- 15158029
TI  - Assessment of macro and microelement accumulation capability of two aquatic
      plants.
AB  - The concentrations of four macroelements (C, N, P, S) and eight trace metals (Cd,
      Cr, Cu, Fe, Mn, Ni, Pb, Zn) were measured in the leaves and roots of the emergent
      plant, Phragmites communis Trin., and in the shoots and roots of the submersed
      Najas marina L., taken from Lake Averno (Naples, Italy). Phragmites communis
      leaves showed higher concentrations of carbon, nitrogen and phosphorus than
      roots, while the roots exhibited significantly higher concentrations of sulphur
      and trace metals. Najas marina roots also showed higher concentrations of sulphur
      and trace metals than shoots, but these differences were less marked than in
      Phragmites communis except for sulphur. Sulphur was the only macronutrient to
      show the highest concentrations in the roots. Phragmites communis roots had
      higher values of Cr, Cu, Fe, Mn and Ni than Najas marina roots. By contrast, Cd,
      Cr, Fe, Ni, Pb and Zn concentrations were higher in Najas marina shoots than in
      Phragmites communis leaves. Phragmites communis, available through the year,
      showing high capability to accumulate trace metals in the roots, appears a good
      monitor of lake contamination, better than Najas marina.

PMID- 15158030
TI  - Effect of anions and cations on cadmium sorption kinetics from aqueous solutions
      by chitin: experimental studies and modeling.
AB  - The effect of ions, including Na(+), Mg(2+), Ca(2+), Cl(-), SO(4)(2-) and CO(3)(2
      ), at various initial concentrations, on the kinetics of cadmium sorption by
      chitin was studied at 25 degrees C and free initial pH solution in batch
      conditions. The presence of these ions in solution was found to inhibit the
      uptake of cadmium by chitin to different degrees: sodium and chloride ions have
      no significant effect. For Mg(2+), Ca(2+), SO(4)(2-) and CO(3)(2-) ions, the
      effects ranged from a large inhibition of cadmium by Ca(2+) and CO(3)(2-) to a
      weak inhibition by Mg(2+) and SO(4)(2-). These results indicate that the uptake
      sites of these ions are the same. No ion was found to enhance cadmium uptake. The
      results also showed that the kinetics of sorption are best described by a pseudo
      second-order expression than a first or second-order model.

PMID- 15158031
TI  - Trichloroacetic acid cycling in Sitka spruce saplings and effects on sapling
      health following long term exposure.
AB  - Trichloroacetic acid (TCA, CCl(3)COOH) has been associated with forest damage but
      the source of TCA to trees is poorly characterised. To investigate the routes and
      effects of TCA uptake in conifers, 120 Sitka spruce (Picea sitchensis (Bong.)
      Carr) saplings were exposed to control, 10 or 100 microg l(-1) solutions of TCA
      applied twice weekly to foliage only or soil only over two consecutive 5-month
      growing seasons. At the end of each growing season similar elevated TCA
      concentrations (approximate range 200-300 ng g(-1) dwt) were detected in both
      foliage and soil-dosed saplings exposed to 100 microg l(-1) TCA solutions showing
      that TCA uptake can occur from both exposure routes. Higher TCA concentrations in
      branchwood of foliage-dosed saplings suggest that atmospheric TCA in solution is
      taken up indirectly into conifer needles via branch and stemwood. TCA
      concentrations in needles declined slowly by only 25-30% over 6 months of winter
      without dosing. No effect of TCA exposure on sapling growth was measured during
      the experiment. However at the end of the first growing season needles of
      saplings exposed to 10 or 100 microg l(-1) foliage-applied TCA showed
      significantly more visible damage, higher activities of some detoxifying enzymes,
      lower protein contents and poorer water control than needles of saplings dosed
      with the same TCA concentrations to the soil. At the end of each growing season
      the combined TCA storage in needles, stemwood, branchwood and soil of each
      sapling was <6% of TCA applied. Even with an estimated half-life of tens of days
      for within-sapling elimination of TCA during the growing season, this indicates
      that TCA is eliminated rapidly before uptake or accumulates in another
      compartment. Although TCA stored in sapling needles accounted for only a small
      proportion of TCA stored in the sapling/soil system it appears to significantly
      affect some measures of sapling health.

PMID- 15158032
TI  - Organotin compounds in precipitation, fog and soils of a forested ecosystem in
      Germany.
AB  - Organotin compounds (OTC) are highly toxic pollutants and have been mostly
      investigated so far in aquatic systems and sediments. The concentrations and
      fluxes of different organotin compounds, including methyl-, butyl-, and octyltin
      species in precipitation and fog were investigated in a forested catchment in NE
      Bavaria, Germany. Contents, along with the vertical distribution and storages in
      two upland and two wetland soils were determined. During the 1-year monitoring,
      the OTC concentrations in bulk deposition, throughfall and fog ranged from 1 ng
      Sn l(-1) to several ten ng Sn l(-1), but never over 200 ng Sn l(-1). The OTC
      concentrations in fog were generally higher than in throughfall and bulk
      deposition. Mono-substituted species were the dominant Sn species in
      precipitation (up to 190 ng Sn l(-1)) equaling a flux of up to 70 mg Sn ha(-1) a(
      1). In upland soils, OTC contents peaked in the forest floor (up to 30 ng Sn g(
      1)) and decreased sharply with the depth. In wetland soils, OTC had slightly
      higher contents in the upper horizons. The dominance of mono-substituted species
      in precipitation is well reflected in the contents and storages of OTC in both
      upland and wetland soils. The ratios of OTC soil storages to the annual
      throughfall flux ranged from 20 to 600 years. These high ratios are probably due
      to high stability and low mobility of OTC in soils. No evidence was found for
      methylation of tin in the wetland soils. In comparison with sediments,
      concentrations and contents of organotin in forest soils are considerably lower,
      and the dominant species are less toxic. It is concluded that forested soils may
      act as sinks for OTC deposited from the atmosphere.

PMID- 15158033
TI  - Polybrominated diphenyl ethers (PBDEs) and their methoxylated derivatives in pike
      from Swedish waters with emphasis on temporal trends, 1967-2000.
AB  - Temporal trends of five tetra- to hexabromodiphenyl ethers [BDE47, BDE99, BDE100,
      BDE153 and BDE154) and two methoxy-tetraBDEs [6-methoxy-2,2',4,4'- tetraBDE (6
      MeO-BDE47) and 2'-methoxy-2,3',4,5'- tetraBDE (2'-MeO-BDE68)] in pike from Lake
      Bolmen for the years 1967-2000, are presented. All BDE congeners show increasing
      trends up to the mid-1980s (Sigma5PBDE from 60 to 1600 pg/g wet weight in 1989,
      i.e. a more than 25-fold increase), and then decrease or level off. The
      decreasing trends of PBDEs after the 1980s were considerably slower in the
      present study than was found in a study of an environmental matrix from the
      Baltic Proper covering the same time period. This difference suggests local
      sources near Lake Bolmen. The MeO-BDEs show initially decreasing concentrations,
      which for 6-MeO-BDE47 continues until the early 1990s. The concentrations of 6
      MeO-BDE47 in herring from five locations along the Swedish coast increased from
      south to north in the Baltic Sea. No correlation between the concentrations of
      the BDE congeners and the MeO-BDEs was observed, indicating sources other than
      PBDEs for these compounds. The presence of MeO-BDEs in fish from lakes with
      different characteristics suggests a natural production not favoured by
      eutrophication, or dependent on sampling season and geographical location.

PMID- 15158034
TI  - Responses of hybrid poplar clones and red maple seedlings to ambient O(3) under
      differing light within a mixed hardwood forest.
AB  - The responses of ramets of hybrid poplar (Populus spp.) (HP) clones NE388 and
      NE359, and seedlings of red maple (Acer rubrum, L.) to ambient ozone (O(3)) were
      studied during May-September of 2000 and 2001 under natural forest conditions and
      differing natural sunlight exposures (sun, partial shade and full shade). Ambient
      O(3) concentrations at the study site reached hourly peaks of 109 and 98 ppb in
      2000 and 2001, respectively. Monthly 12-h average O(3) concentrations ranged from
      32.3 to 52.9 ppb. Weekly 12-h average photosynthetically active radiation (PAR)
      within the sun, partial shade and full shade plots ranged from 200 to 750, 50 to
      180, and 25 to 75 micromol m(-2) s(-1), respectively. Ambient O(3) exposure
      induced visible foliar symptoms on HP NE388 and NE359 in both growing seasons,
      with more severe injury observed on NE388 than on NE359. Slight foliar symptoms
      were observed on red maple seedlings during the 2001 growing season. Percentage
      of total leaf area affected (%LAA) was positively correlated with cumulative O(3)
      exposures. More severe foliar injury was observed on plants grown within the full
      shade and partial shade plots than those observed on plants grown within the sun
      plot. Lower light availability within the partial shade and full shade plots
      significantly decreased net photosynthetic rate (Pn) and stomatal conductance
      (g(wv)). The reductions in Pn were greater than reductions in g(wv), which
      resulted in greater O(3) uptake per unit Pn in plants grown within the partial
      shade and full shade plots. Greater O(3) uptake per unit Pn was consistently
      associated with more severe visible foliar injury in all species and/or clones
      regardless of differences in shade tolerance. These studies suggest that plant
      physiological responses to O(3) exposure are likely complicated due to multiple
      factors under natural forest conditions.

PMID- 15158035
TI  - Influence of light fleck and low light on foliar injury and physiological
      responses of two hybrid poplar clones to ozone.
AB  - Five-month old hybrid poplar clones NE388 and NE359 were exposed to square-wave
      30, 55, and 80 ppb O(3) (8 h/day, 7 day/week) under constant high light (HL) and
      light fleck (LF) during 28 May-29 June 1999, and exposed to 30 and 55 ppb O(3)
      under HL, LF, and constant low light (LL) during 22 May-28 June 2000 within
      Continuously Stirred Tank Reactors (CSTR) in a greenhouse. Ramets of these two
      hybrid clones received similar total photosynthetically active radiation (PAR)
      within the LF and LL treatments. Visible foliar symptoms, leaf gas exchange, and
      growth were measured. More severe O(3) induced foliar symptoms were observed on
      ramets within the LF and LL treatments than within the HL treatment for both
      clones. The LF treatment resulted in significantly greater foliar injury than the
      LL treatment for NE388. The LF and LL treatments generally resulted in lower
      photosynthetic rates (Pn) for both clones, but did not affect stomatal
      conductance (g(wv)); therefore, the ratios of g(wv)/Pn and the O(3) uptake/Pn
      were greatest in plants grown under the LF treatment, followed by those grown
      under LL treatment; plants grown under HL had the lowest ratios of g(wv)/Pn and
      O(3) uptake/Pn. Greater ratios of g(wv)/Pn and O(3) uptake/Pn were consistently
      associated with more severe visible foliar symptoms. The negative impacts of the
      LF treatment on growth were greater than those of the LL treatment. Results
      indicate that not only the integral, but also the pattern of photo flux density,
      may affect carbon gain in plants. Increased foliar injury may be expected under
      light fleck conditions due to the limited repair capacity as a result of
      continuity of O(3) uptake while photosynthesis decreases under LL conditions.

PMID- 15158036
TI  - Tracing sewage pollution using linear alkylbenzenes (LABs) in surface sediments
      at the south end of the Southern California Bight.
AB  - Distribution and isomeric composition of LABs in surface marine sediments were
      evaluated at the southern end of the southern California Bight. LABs are used as
      tracers of wastewater discharges. The area studied extends from the Mexico-USA
      border to the Todos Santos Bay, Baja California in the south. The area was
      partitioned into a northern, central and a southern stratum. GC-MS was used for
      the analysis of LABs concentration. The average value of total LABs concentration
      was 17.4, 32.0 and 24.9 ng/g for the north, central and southern strata,
      respectively. LABs were not correlated with either sediments grain size (%<63
      microm) or sediment organic carbon contents. The highest concentrations values of
      LABs were found in the northern and central strata near the 200 m isobath. Based
      on the I/E index, the estimated average percentage degradation was 21.3, 15.9,
      and 8.4% for the northern, central and southern strata respectively. Based on the
      isomeric composition of LABs, the largest degradation value was found in the
      northern stations. Internal isomers did not show significant enrichment, however,
      short-chained isomers (LAB(10), LAB(11)) showed enrichment. It was found that 67
      out of the 68 stations measured had concentrations above detection limits. This
      suggests extensive contact of wastewater discharges with marine sediments in the
      area. An estimate of the amount of LABs per year based on detergent consumption
      per capita is provided.

PMID- 15158038
TI  - Occurrence of PAHs, PCBs and organochlorine pesticides in the Tonghui River of
      Beijing, China.
AB  - Tonghui River, a typical river in Beijing, People's Republic of China, was
      studied for its water and sediment quality, by determining the levels of 16
      polycyclic aromatic hydrocarbons (PAHs), 12 polychlorinated biphenyls (PCBs) and
      18 organochlorine pesticides in water and sediment samples. Total PAHs, PCBs and
      organochlorine pesticides concentrations in water varied from 192.5 to 2651 ng/l,
      31.58-344.9 ng/l and 134.9-3788 ng/l, respectively. The total PAHs, PCBs and
      organochlorine pesticides concentrations in surficial sediments were 127-928
      ng/g, 0.78-8.47 ng/g and 1.79-13.98 ng/g dry weight, respectively. The results
      showed that the concentration of these selected organic pollutants in sediment
      was higher than those in surface water. It may be due to the fact that organic
      hydrophobic pollutants tend to stay in the sediments. The PAHs were dominated by
      2-, 3-ring components in water samples and by 3- and 4-ring compounds in
      sediment. For organochlorines, alpha-HCH, delta-HCH, Heptachlor, Endosulfan II,
      DDT are the major organochlorine pesticides in water while Heptachlor, Dieldrin
      and DDE composed of 95% of total organochlorine pesticides in sediment. For HCHs
      (HCHs=alpha-HCH+beta-HCH+gamma-HCH+delta-HCH), the predominance of alpha-HCH of
      total HCHs were clearly observed in water and sediment. PCB18, PCB31 and PCB52
      were predominant in water, on average these compounds collectively accounted for
      67% of total PCBs. But in sediment, the predominant compounds were PCB28, PCB31
      and PCB153, which accounted for 71% of total PCBs in sediment. The levels of
      micro pollutants in our study areas were compared with other studies.

PMID- 15158037
TI  - Sediment trace metal profiles in lakes of Killarney Park, Canada: from regional
      to continental influence.
AB  - The lakes in Killarney Provincial Park (KPP) located 40-60 km southwest of
      Sudbury, Ontario are beginning to recover after decades of being severely
      affected by acidification and atmospheric pollutants. Detailed profiles of acid
      recoverable trace elements (As. Cd, Cu, Co. Fe, Mn, Ni, Pb and Zn) were obtained
      after aqua regia digestion and ICP-OES analysis of sediment cores taken from six
      Park lakes. Results permitted the identification of two types of profiles. The
      first type applies to elements such as Fe, Mn, As and Co for which historical
      deposition and recent recovery are strongly masked by diagenetic remobilization.
      The second type of profile applies to elements such as Cd, Cu, Ni, Pb and Zn on
      which the history of industrialisation in North America and mining activities in
      Sudbury can be superimposed. Based on sediment data of trace elements less
      affected by diagenetic remobilization (Cd, Cu, Ni, Pb, Zn), chemical recovery
      indices can be estimated from depth profiles. Indices of maximum (C(p)) and
      surface (C(s)) contamination were calculated by dividing the concentration of a
      given metal by the pre-industrial level. The ratio of the two indices provided a
      simple estimation of the chemical recovery of lakes that does not consider the
      influence of the watershed or the lake pH. Profiles of metals in sediment of KPP
      complement the water quality monitoring data and tend to indicate that this area
      is in transition from dominant influence of regional pollution sources to
      becoming controlled by continental atmospheric deposition.

PMID- 15158039
TI  - Macroinvertebrate response to acid mine drainage: community metrics and on-line
      behavioural toxicity bioassay.
AB  - The hypothesis is tested that toxicity of acid mine drainage can be detected by a
      selection of existing macroinvertebrate community and bioindicator metrices
      supplemented by toxicity tests with the local mosquitofish Gambusia holbrooki
      Girard and the shrimp Atyaephyra desmaresti Millet. The behavioural responses of
      A. desmaresti to acid mine drainage were recorded in the Multispecies Freshwater
      Biomonitor, based on behaviour and survival as parameters. Bioassessment methods
      were based on community diversity, structure, function, and bioindicators and
      supplemented by chemical analysis (temperature, pH, metals). The Biological
      Monitoring Working Party adapted for the Iberian Peninsula, the number of
      predators (Coleoptera, Hemiptera) and the number of Ephemeroptera and Trichoptera
      taxa differentiated the sites well. The on-line toxicity test revealed pH
      dependent acute toxicity of the acid mine drainage for the shrimp (LC(50)-48 h:
      pH-AMD=5.8) and a pH- dependent decrease in locomotory activity with the lowest
      observed-response-times (LORTs) within 5 h of exposure. Shrimp were more
      sensitive to acid mine drainage than fish (LC(50)-48 h: pH-AMD=4.9). A new
      multimetric index combining toxicity testing and bioassessment methods is
      proposed.

PMID- 15158040
TI  - Effect of cropping and tillage on the dissipation of PAH contamination in soil.
AB  - This study examined the effect of regular tillage and cropping on the dissipation
      rate of PAHs in contaminated soil. Lysimeters were placed under natural climatic
      conditions for 2 years and designed to measure the concentration of PAHs in soil
      and leachates and their toxicity. The soil initially contained 2077 microg PAHs
      g(-1). The largest decrease in PAHs concentration occurred during the first 6
      months. No further significant decrease was observed after this time. The surface
      soil layer always contained significantly less PAHs than the deeper layer,
      regardless of the treatments. Less than 8.4 x 10(-8)% of the PAH initially
      present in the soil (e.g. less or equal to 33 microg PAHs per lysimeter) were
      leached from the soils during the experiment and the leachates presented no
      toxicity (as measured by the Microtox test). The toxicity of the soils decreased
      with time and was significantly lower on the cropped soil compared to the other
      treatments, despite the residual concentration of PAHs being the highest in this
      soil. This study demonstrated that the dissipation rates of PAHs were slow after
      using natural attenuation even when tillage and cropping were performed at the
      soil surface.

PMID- 15158041
TI  - Scale-dependence of land use effects on water quality of streams in agricultural
      catchments.
AB  - The influence of land use on water quality in streams is scale-dependent and
      varies in time and space. In this study, land cover patterns and stocking rates
      were used as measures of agricultural development in two pasture and one native
      grassland catchment in New Zealand and were related to water quality in streams
      of various orders. The amount of pasture per subcatchment correlated well to
      total nitrogen and nitrate in one catchment and turbidity and total phosphorous
      in the other catchment. Stocking rates were only correlated to total phosphorous
      in one pasture catchment but showed stronger correlations to ammonium, total
      phosphorous and total nitrogen in the other pasture catchment. Winter and spring
      floods were significant sources of nutrients and faecal coliforms from one of the
      pasture catchments into a wetland complex. Nutrient and faecal coliform
      concentrations were better predicted by pastural land cover in fourth-order than
      in second-order streams. This suggests that upstream land use is more influential
      in larger streams, while local land use and other factors may be more important
      in smaller streams. These temporal and spatial scale effects indicate that water
      monitoring schemes need to be scale-sensitive.

PMID- 15158042
TI  - Analysis of gene expression data using functional principal components.
AB  - The large amount of data involved in DNA microarrays implies the development of
      efficient computer algorithms to analyze the gene expressions, and thus to study
      the transcriptome. Numerous techniques already exist and we propose a new method
      based on the key idea that gene profiles may be considered as continuous curves.
      The analysis of the set of curves stemming from the DNA microarray may be then
      performed using a functional analysis which can exhibit the main modes of
      variations in this set, gather genes with similar variations and extract
      characteristic parameters of gene profiles. We aim here at introducing this
      method, called the Functional Principal Component Analysis. A prospective study
      has been performed on two available datasets, concerning on the one hand the
      sporulation data of the Saccharomyces cerevisiae, and on the other hand data of
      tumor cell lines. Results are very promising: the method is able to extract
      characteristic parameters from the datasets, to extract significant modes of
      variations in the set of gene profiles, and to link these variations to
      biological processes already studied in literature.

PMID- 15158043
TI  - Design and implementation of an SVM-based computer classification system for
      discriminating depressive patients from healthy controls using the P600 component
      of ERP signals.
AB  - A computer-based classification system has been designed capable of
      distinguishing patients with depression from normal controls by event-related
      potential (ERP) signals using the P600 component. Clinical material comprised 25
      patients with depression and an equal number of gender and aged-matched healthy
      controls. All subjects were evaluated by a computerized version of the digit span
      Wechsler test. EEG activity was recorded and digitized from 15 scalp electrodes
      (leads). Seventeen features related to the shape of the waveform were generated
      and were employed in the design of an optimum support vector machine (SVM)
      classifier at each lead. The outcomes of those SVM classifiers were selected by a
      majority-vote engine (MVE), which assigned each subject to either the normal or
      depressive classes. MVE classification accuracy was 94% when using all leads and
      92% or 82% when using only the right or left scalp leads, respectively. These
      findings support the hypothesis that depression is associated with dysfunction of
      right hemisphere mechanisms mediating the processing of information that assigns
      a specific response to a specific stimulus, as those mechanisms are reflected by
      the P600 component of ERPs. Our method may aid the further understanding of the
      neurophysiology underlying depression, due to its potentiality to integrate
      theories of depression and psychophysiology.

PMID- 15158044
TI  - Data quality aspects of a database for abdominal septic shock patients.
AB  - Since many years, medical researchers have investigated the mechanisms that may
      cause a septic shock. Despite many approaches that analyzed smaller parts of the
      relevant data or single variables, respectively, no larger database with all the
      possible relevant data existed. Our work was to bridge this gap. We built a large
      database for abdominal septic shock patients. While building it, we were
      confronted with many problems concerning the database realization and the data
      quality. Thus, we will demonstrate how we built our database and how we assured
      data quality. This is of interest for all medical or computer scientists who are
      concerned with building medical databases with retrospective data, e.g. for data
      mining purposes.

PMID- 15158045
TI  - Software for interactive segmentation of the carotid artery from 3D black blood
      magnetic resonance images.
AB  - A semiautomatic algorithm for segmenting organ surfaces from 3D medical images is
      presented in this work. The algorithm is based on a deformable model, and allows
      the user to initialize the model by combining and molding primitive shapes such
      as cylinders and spheres to form an initial approximate model of the organ
      surface. The initial model is automatically deformed to better fit organ
      boundaries. The algorithm was applied to segment the carotid bifurcation from 3D
      black blood magnetic resonance (MR) images of 5 subjects. The algorithm-segmented
      surfaces were compared to surfaces segmented manually by an experienced user. On
      average, approximately 3 min were required to segment an image using the
      algorithm, whereas 1h was required for manual segmentation. The average distance
      between corresponding points on the manually and algorithm-segmented surfaces was
      0.37 mm, whereas the average maximum distance was 2.03 mm. Moreover, algorithm
      segmented surfaces exhibited less intra-operator variability than those segmented
      manually.

PMID- 15158046
TI  - Adjusted survival curves with inverse probability weights.
AB  - Kaplan-Meier survival curves and the associated nonparametric log rank test
      statistic are methods of choice for unadjusted survival analyses, while the
      semiparametric Cox proportional hazards regression model is used ubiquitously as
      a method for covariate adjustment. The Cox model extends naturally to include
      covariates, but there is no generally accepted method to graphically depict
      adjusted survival curves. The authors describe a method and provide a simple
      worked example using inverse probability weights (IPW) to create adjusted
      survival curves. When the weights are non-parametrically estimated, this method
      is equivalent to direct standardization of the survival curves to the combined
      study population.

PMID- 15158047
TI  - A computer software for simulating single-compartmental model of neurons.
AB  - In this paper, a new computer software package, Yalzer, is introduced for
      simulating single-compartmental model of neurons. Passive or excitable membranes
      with voltage-gated ion channels can be modeled, and current clamp and voltage
      clamp experiments can be simulated. In the Yalzer, first-order differential
      equations used to define the dynamics of the gate variables and the membrane
      potential are solved by two separate integration methods with variable time
      steps: forward Euler and exponential Euler methods. Outputs of the simulation are
      shown on a spreadsheet template for allowing flexible data manipulation and can
      be graphically displayed. The user can define the model in detail, and examine
      the excitability of the model and the dynamics of voltage-gated ion channels. The
      software package addresses to ones who want to run simple simulations of neurons
      without need to any programming language skills or expensive software. It can
      also be used for educational purposes.

PMID- 15158048
TI  - A SAS macro for estimating transition probabilities in semiparametric models for
      recurrent events.
AB  - In many clinical studies involving event history analysis, the event of interest
      is non-fatal and may occur more than once for each subject. Models based on the
      theory of counting processes have been developed to deal with such data, the
      recurrences being considered as transitions in a Markovian process. Under this
      setting, the experimental units can move between states over time, and it is
      possible to estimate the corresponding transition probabilities employing
      regression models that incorporate the influence of covariates. Despite of this,
      most of the softwares are concerned only in the estimation of regression
      parameters and do not provide transition probabilities estimates. The aim of this
      paper is to present a SAS macro developed to estimate the transition
      probabilities, considering three approaches for the regression modeling. The
      macro is flexible enough to allow the user to select the model to be fit
      providing, for a given set of covariates, plots of the estimates for the
      predicted transition probabilities as a function of time.

PMID- 15158049
TI  - OptiRNAi, an RNAi design tool.
AB  - RNA interference (RNAi), a recently developed reverse genetics tool, has many
      advantages compared to traditional gene knockout methods. Appropriate selection
      of double stranded RNAs identical to a specific region(s) of the target gene is
      critical for the successful implementation of this technology. Recently, Elbashir
      et al. [Methods 26 (2002) 199] has established empirical criteria for siRNA
      sequence selection that significantly improved the success rate for RNAi
      attempts. We have developed OptiRNAi, a computational tool, which uses the
      Elbashir et al. criteria to predict appropriate target sequences for siRNA
      production. Specificity of these siRNAs for the target of interest can then be
      assessed by the investigator using the embedded Blast search engine optimized for
      RNAi design. Thus, OptiRNAi is an efficient and user friendly tool for RNAi
      design based on criteria that are more stringent than other available tools.

PMID- 15158050
TI  - Automated quantitative analysis of angiogenesis in the rat aorta model using
      Image-Pro Plus 4.1.
AB  - This paper explains the automated image-processing steps for the quantification
      of microvascular growth formation in the rat thoracic aortic ring model, an ex
      vivo model using excised rings of rat aorta embedded in a collagen matrix which
      produce outgrowths of microvessels. This model of angiogenesis is useful to study
      the mechanism by which external agents inhibit or stimulate endothelial cell
      proliferation and tube formation. The manual quantification of blood vessel
      growth in this model is normally a time-consuming, error prone process. Former
      automated image analysis methods of the ring model are outdated and cannot be
      used with current software technology. A macro was created using Image-Pro Plus
      4.1 software which was chosen for image analysis because it allows a high degree
      of control and replication of image-processing steps. The accuracy of this macro
      was determined by comparing automated counts to manual counts in 161 aortic
      rings. The square root of the manual count versus the square root of the
      automated count resulted in a root mean square value of 0.8305.

PMID- 15158051
TI  - The regulatory software of cellular metabolism.
AB  - Understanding the regulation of metabolic pathways in the cell is like unraveling
      the 'software' that is running on the 'hardware' of the metabolic network.
      Transcriptional regulation of enzymes is an important component of this software.
      A recent systematic analysis of metabolic gene-expression data in Saccharomyces
      cerevisiae reveals a complex modular organization of co-expressed genes, which
      could increase our ability to understand and engineer cellular metabolic
      functions.

PMID- 15158052
TI  - Is whole-culture synchronization biology's 'perpetual-motion machine'?
AB  - Whole-culture or batch synchronization cannot, in theory, produce a synchronized
      culture because it violates a fundamental law that proposes that no batch
      treatment can alter the cell-age order of a culture. In analogy with the history
      of perpetual-motion machines, it is suggested that the study of these whole
      culture 'synchronization' methods might lead to an understanding of general
      biological principles even though these methods cannot be used to study the
      normal cell cycle.

PMID- 15158053
TI  - Reply: whole-culture synchronization - effective tools for cell cycle studies.
AB  - Studies of gene expression during the eukaryotic cell cycle in whole-culture
      synchronized cultures have been published using many methodologies. These
      procedures alter the state of the cell cycle for a population of cells, rather
      than purifying a population of cells that are in the same state. Criticism of
      these methods (e.g. see Cooper, this issue, pp. 266-269, ) suggests that these
      studies are flawed, and posits that such methodologies cannot be used to study
      the cell cycle because they alter the size and age distributions of the cultures.
      We believe that whole-culture cell cycle studies work even though they alter the
      size and age distributions: these cells still progress through the cell cycle and
      although we do not suggest that the methods are perfect, we will explain how
      these microarray studies have successfully identified cell cycle regulated genes
      and why these results are biologically meaningful.

PMID- 15158054
TI  - Rejoinder: whole-culture synchronization cannot, and does not, synchronize cells.
AB  - There have been numerous proposals suggesting that whole-culture methods - in
      which all cells in a growing culture are treated identically - can synchronize
      cells. An explicit defense of these methods has been presented (Spellman and
      Sherlock, this issue, pp. 270-273, ). Here, this defense of whole-culture
      'synchronization' is subjected to a critical evaluation leading to the conclusion
      that whole-culture synchronization cannot synchronize cells - at all. Whole
      culture methods cannot produce a set of cells that reflects the size and genome
      composition of cells of any particular cell-cycle age during the normal cell
      cycle. Thus, in addition to the well-recognized problem of artifacts, it is
      proposed that experiments using whole-culture treatments (usually starvation or
      inhibition methods) are not suitable for cell-cycle analysis because these
      methods do not produce a synchronized culture.

PMID- 15158055
TI  - Final words: cell age and cell cycle are unlinked.
AB  - Cooper has a simple belief: that the cell cycle is connected to age and size.
      Furthermore, as a result of this connection in his mind he believes that there
      are no possible manipulations that can operate on a batch culture to synchronize
      cells within the cell cycle, such that those cells can undergo a semblance of a
      normal cell cycle. His formulation of this argument is as a 'fundamental law',
      the law of conservation of cell-age order (LCCAO). The first part of this law -
      'there is no batch treatment of the culture that can lead to an alteration of the
      cell-age order' - can probably be proved true, in the mathematical sense, and
      certainly makes intuitive sense. Unfortunately the corollaries of this law are
      rather suspect, drawing inferences from cell age to cell size to the cell cycle.

PMID- 15158056
TI  - Nucleus transfer in mammals: noninvasive approaches for the preparation of
      cytoplasts.
AB  - The production of cloned animals is a difficult and complex procedure that
      requires two basic steps. First, the cytoplast must be prepared by the
      enucleation of metaphase II oocytes. Second, the nucleus is transferred either by
      fusion or by direct microinjection into the cytoplast. The preparation of
      cytoplasts is a crucial step because they must be able to reprogram the
      transferred nucleus and to secure the development of reconstructed embryos.
      Moreover, the classical mechanical enucleation of metaphase II oocytes is rather
      technically difficult, requiring good equipment and considerable
      micromanipulation skill. For this reason the simplification of this step is
      permanently in the centre of interest of those scientists who are involved in the
      production of clones.

PMID- 15158057
TI  - Governing UK Biobank: the importance of ensuring public trust.
AB  - In the autumn of 2003, UK Biobank published the first draft of its Ethics and
      Governance Framework. Subsequently, this document has been available for
      interested parties to comment on and the UK Biobank Board of Directors is
      expected to adopt the final version in 2004. Here, we aim to contribute to this
      process and highlight to a wider audience some of the inconsistencies in the
      issues of consent, governance and right of withdrawal that emerge from the draft
      of the Framework. These issues will have implications for securing the public
      trust and long-term support that the success of the project depends on.
      Therefore, they must be considered carefully because the UK Biobank will be the
      first ever genetic database of a general population of this size to become
      operational, and will be used as a model for other projects of this kind.

PMID- 15158058
TI  - The contribution of farm animals to human health.
AB  - Farm animals and their products have a longstanding and successful history of
      providing significant contributions to human nutrition, clothing, facilitation of
      labour, research, development and medicine and have thus been essential in
      improving life expectancy and human health. With the advent of transgenic
      technologies the potential of farm animals for improving human health is growing
      and many areas remain to be explored. Recent breakthroughs in reproductive
      technologies, such as somatic cloning and in vitro embryo production, and their
      merger with molecular genetic tools, will further advance progress in this field.
      Here, we have summarized the contribution of farm animals to human health,
      covering the production of antimicrobial peptides, dietary supplements or
      functional foods, animals used as disease models and the contribution of animals
      to solving urgent environmental problems and challenges in medicine such as the
      shortage of human cells, tissues and organs and therapeutic proteins. Some of
      these areas have already reached the level of preclinical testing or commercial
      application, others will be further advanced only when the genomes of the animals
      concerned have been sequenced and annotated. Provided the necessary precautions
      are being taken, the transmission of pathogens from animals to humans can be
      avoided to provide adequate security. Overall, the promising perspectives of farm
      animals and their products warrant further research and development in this
      field.

PMID- 15158059
TI  - Biotechnological applications of bioluminescence and chemiluminescence.
AB  - Recent progress in molecular biology has made available several biotechnological
      tools that take advantage of the high detectability and rapidity of
      bioluminescence and chemiluminescence spectroscopy. These developments provide
      inroads to in vitro and in vivo continuous monitoring of biological processes
      (e.g. gene expression, protein-protein interaction and disease progression), with
      clinical, diagnostic and drug discovery applications. Furthermore, combining
      luminescent enzymes or photoproteins with biospecific recognition elements at the
      genetic level has led to the development of ultrasensitive and selective
      bioanalytical tools, such as recombinant whole-cell biosensors, immunoassays and
      nucleic acid hybridization assays. The high detectability of the luminescence
      analytical signal makes it appropriate for miniaturized bioanalytical devices
      (e.g. microarrays, microfluidic devices and high-density-well microtiter plates)
      for the high-throughput screening of genes and proteins in small sample volumes.

PMID- 15158060
TI  - Targeted gene therapy: frontiers in the development of 'smart drugs'.
AB  - Chronic diseases, particularly malignancies and immune-mediated inflammatory
      diseases (IMIDs), are a challenging frontier for clinical diagnosis and
      treatment, as well as for biomedical research. Current treatment regimens are
      frequently insufficient and thus new treatment strategies are needed. Novel
      therapies for disabling such diseases should provide improvements with respect to
      safety, efficacy and cost. To fulfill these three key criteria, recent research
      efforts have focused on the development of 'smart drugs'. This review highlights
      some examples of the rapidly expanding possibilities that current biotechnology
      has to offer in the development of novel therapeutic strategies for complex
      diseases such as IMIDs. Special attention is given to advances in, and
      limitations of, controlled and targeted gene product application in inflammatory
      diseases.

PMID- 15158061
TI  - Taming plastids for a green future.
AB  - Plant genetic engineering will probably contribute to the required continued
      increase in agricultural productivity during the coming decades, and moreover,
      plants can potentially provide inexpensive production platforms for
      pharmaceuticals and nutraceuticals. With the advent of technologies for altering
      the genetic information inside chloroplasts, a new attractive target for genetic
      engineering has become available to biotechnologists. Potential advantages over
      conventional nuclear transformation include high transgene expression levels and
      increased biosafety because of maternal organelle inheritance in most crops. This
      review summarizes the state of the art in chloroplast genetic engineering and
      describes how reverse genetics approaches enhance our understanding of
      photosynthesis and other important chloroplast functions. Furthermore, promising
      strategies by which chloroplast genetic engineering might contribute to the
      successful modification of plant metabolism are discussed.

PMID- 15158062
TI  - Development of enzyme-linked immunosorbent assay for detecting antibodies to
      replication-competent murine leukemia virus.
AB  - A method for detecting the antibodies to replication-competent retrovirus (RCR)
      was developed. Specific fragments of murine leukemia virus (MLV) Gag or Env
      protein were cloned and expressed in Escherichia coli, and used subsequently to
      develop the ELISA system. It was found that CA of Gag and SU of Env, but not the
      transmembrane portion of Env, could be used in ELISA. ELISA conditions such as
      coating buffer and blocking solution were optimized using sera obtained from mice
      immunized with amphotropic MLV particles. In an optimized ELISA system, serum
      samples from normal healthy individuals provided very low absorbance values.
      ELISA was performed using serum samples from patients who had received skin
      fibroblasts engineered with MLV-based retroviral vector. Experimental samples
      presented absorbance values comparable to those found with control serum samples
      from normal, healthy individuals, showing no evidence of RCR infection.

PMID- 15158063
TI  - Methods for detecting the HSV-1 LAT anti-apoptosis activity in virus infected
      tissue culture cells.
AB  - Plasmids expressing the herpes simplex virus type 1 (HSV-1) latency-associated
      transcript (LAT) reduce apoptosis in transient transfection assays in tissue
      culture. LAT also reduces apoptosis in the context of the virus in trigeminal
      ganglia of rabbits and mice at approximately 6-7 days post-infection during the
      switch from acute to latent HSV-1 infection, a time at which LAT is the only
      abundantly transcribed viral gene. Analysis of LAT's anti-apoptosis function is
      complicated in tissue culture by the expression of at least five additional viral
      gene products that can block apoptosis, and by the fact that apoptosis usually
      occurs in only a fraction of the cells. Here, we present two approaches for
      detecting LAT's anti-apoptosis activity in the context of the whole virus in
      tissue culture. Using a combination of serum starvation to both partially
      synchronize the cells and induce apoptosis, and Hoechst staining to detect
      chromatin condensation, we found that there was a small window of time post
      infection during which Schwann cells infected with the LAT(-) mutant dLAT2903
      reproducibly had more apoptotic nuclei than identically treated cells infected
      with the LAT(+) parental virus HSV-1 strain McKrae. Using serum starvation and/or
      UV treatment and a method to isolate fragmented DNA away from large chromosomal
      DNA, we found a similar window of time post-infection during which Neuro2A cells
      infected with dLAT2903 had increased DNA fragmentation (as judged by a DNA
      laddering assay) compared to identically treated cells infected with wild type
      McKrae or the LAT(+) marker rescued dLAT2903R virus. These assays should permit
      the use of culture assays, rather than labor intensive animal models, to examine
      LAT's anti-apoptosis activity in the context of the virus in a large number of
      existing LAT mutant viruses.

PMID- 15158064
TI  - Ultra-sensitive detection of two garlic potyviruses using a real-time fluorescent
      (Taqman) RT-PCR assay.
AB  - A method for the detection of Onion yellow dwarf virus (OYDV) and Leek yellow
      stripe virus (LYSV), the two most prevalent garlic potyviruses, has been
      developed that combines IC-RT-PCR/RT-PCR with the use of TaqMan probes.
      Comparisons with ELISA results obtained with identical OYDV and LYSV infected
      samples showed sensitivity in detecting these viruses increased up to 10(6)-fold.
      OYDV and LYSV were detected using different fluorochromes in the probe, thus
      allowing unequivocal diagnosis for each of them. The polyvalence of the designed
      virus-specific primers and probes was shown through their application to the
      detection of three isolates from very different geographical areas and from
      different hosts. A second version of the method avoids the need for an
      immunocapture step through the performance of a TaqMan RT-PCR assay directly on
      extracts of garlic cloves. This modification on the proposed basic method allows
      the analysis of bulb samples in 3-4h but did not give reproducible results with
      leaves. Both versions of the new diagnostic method bear great potential for their
      implementation in virus-free certification schemes in garlic, a vegetatively
      propagated crop for which such a certification is critical for a high-quality
      product.

PMID- 15158066
TI  - The effect of sample degradation and RNA stabilization on classical swine fever
      virus RT-PCR and ELISA methods.
AB  - Classical swine fever (CSF), also known as hog cholera, is a highly contagious
      viral infection of swine caused by a member of the genus pestivirus of the
      family, Flaviviridae. The need for accurate laboratory diagnosis of CSF is
      particularly important as it is more reliable than clinical diagnosis. CSF is
      endemic in many tropical countries where the climate is characterized by high
      ambient temperature and humidity. This study details the effect of sample quality
      on CSF antigen-capture ELISA (AC-ELISA) and reverse transcriptase-polymerase
      chain reaction (RT-PCR) methods. RT-PCR assessment of AC-ELISA-positive spleen
      samples stored in a conventional glycerol/saline buffer demonstrated that the RT
      PCR was detrimentally affected by poor sample quality. To provide a more accurate
      representation of this effect, a 14 days study was performed to determine the
      effect of tropical ambient conditions on CSF virus-positive spleen samples stored
      in two transport media; glycerol/saline and a proprietary RNA preservation
      solution (RNAlater). A protective effect was demonstrated in both assays with
      RNAlater as samples were positive in both assays until day 14 post-exposure.
      Samples stored in glycerol/saline were negative at RT-PCR at day 3 post-exposure
      although AC-ELISA was still positive at day 14 post-exposure.

PMID- 15158065
TI  - Application of the trak-C HCV core assay for monitoring antiviral activity in HCV
      replication systems.
AB  - The Ortho trak-C immunoassay has recently established detection of the HCV core
      antigen as a viable indirect marker of HCV replication in clinical samples. In
      this study, trak-C is used to monitor HCV replication in three pre-clinical
      models: the cellular HCV replicon system, transient transfection of HCV genomes,
      and the murine Alb-uPa/SCID HCV infection model. All of these systems utilize
      full-length HCV genomes that direct the expression of core, facilitating its
      detection with monoclonal antibodies. When performed with purified protein, the
      assay detects HCV core with a lower limit of detection at 1.5pg, and exhibits
      linear detection up to 100pg. When assaying extracts prepared from Huh-7 clone 21
      5 cells harboring a full-length HCV replicon, core is detectable from as few as
      63 cell equivalents. The assay was used to determine the sensitivity of Huh 21-5
      cells to the antiviral effects of interferon (IFN). Inhibition by IFN-alpha using
      core detection was comparable to that observed using branched-DNA (bDNA 3.0)
      detection of HCV RNA. Replication of transfected full-length HCV 1a Con1 genomes
      in Huh-7 cells was also detectable using the trak-C assay. Finally, in the
      transgenic murine HCV infection model, the course of viral amplification was
      detected from serum using trak-C with kinetics similar to those observed with RNA
      detection. Given its ease of use and the lack of requirement for RNA
      purification, the trak-C assay has several advantages over RNA-based methods of
      viral monitoring.

PMID- 15158067
TI  - Multiplex real-time quantitative RT-PCR assay for hepatitis B virus, hepatitis C
      virus, and human immunodeficiency virus type 1.
AB  - A multiplex real-time quantitative reverse transcription (RT)-PCR assay was
      developed for simultaneous detection, identification and quantification of
      hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus
      type 1 (HIV-1) in plasma or serum samples. Genomic amplification of one virus was
      unaffected by the simultaneous amplification of the other two. Competition
      between HCV and HIV-1 amplifications slightly affected the yield of HIV-1
      amplification. However, quantitation was possible when a single virus was
      present. The 95% detection limits were 30, 167 and 680IU/ml for HBV DNA, HCV RNA
      and HIV-1 RNA, respectively. The multiplex assay detected with similar efficiency
      strains of HBV genotypes A-F, HCV genotypes 1-6, and HIV-1 subtypes A-G. Applied
      to 267 pools of 10 plasmas from blood donors, multiplex screening indicated that
      the assay was reproducible, sensitive, and specific. This assay has the potential
      to be used for large-scale nucleic acid testing (NAT) of blood donations.

PMID- 15158068
TI  - A simple and rapid single-step multiplex RT-PCR to detect Norovirus, Astrovirus
      and Adenovirus in clinical stool samples.
AB  - A single-step multiplex reverse transcription-polymerase chain reaction (RT-PCR)
      assay that detects and identifies Norovirus, Astrovirus and Adenovirus in
      clinical stool samples is described. Four hundred sixty stool samples were tested
      from patients with non-rotavirus acute gastroenteritis, that were either stored
      at -80 degrees C and tested retrospectively, or tested immediately after viral
      nucleic acid extraction in a prospective manner, including outbreaks of
      gastroenteritis that occurred in Germany during the winter of 2003. The multiplex
      RT-PCR was validated against simplex RT-PCR with published primers for Norovirus
      (JV12/JV13 and p289/p290) and Astrovirus (Mon340/348), and against simplex PCR
      for Adenovirus. In both retrospective and prospective settings, the multiplex RT
      PCR was equally sensitive and specific in detecting non-rotavirus infections
      compared with simplex RT-PCR/PCR. The specificity of the multiplex RT-PCR was
      assessed by sequencing of the amplicons that showed high nucleotide identities to
      Norovirus genogroup I/1, I/4, II/2, or II/4 clades, as well as to Astrovirus
      serotypes 1, 2, 4, or 8. The multiplex RT-PCR was also more sensitive than
      Astrovirus and Norovirus antigen enzyme immunoassays (IDEIA, Dako), as well as
      Astrovirus isolation in cell culture. This novel multiplex RT-PCR is an
      attractive technique for the rapid, specific, and cost-effective laboratory
      diagnosis of non-rotavirus acute gastroenteritis.

PMID- 15158069
TI  - A convenient method for positive selection of retroviral producing cells
      generating vectors devoid of selectable markers.
AB  - Early retroviral vectors containing both a therapeutic gene and a dominant
      selectable marker gene, offered some distinct advantages with respect to gene
      therapy, in that they simplified the generation, isolation, and titration of
      retroviral producer cell clones, as well as the evaluation and selection of
      successfully targeted cells. However, a number of problems were engendered by
      this strategy: the promoter driving the selectable marker gene could interfere
      with transcription of the therapeutic gene, and immune responses could be induced
      to cells expressing foreign proteins of selection marker origin. Simplified
      retroviral vectors, which lack a selection marker gene, were constructed to
      address these problems, but the inability to use a selection marker has made
      identification and cloning of virus producing transfected cells a heavy burden.
      To maintain the benefits of simplified retroviral vectors, while providing a
      facile means to select packaging cells transfected with retroviral DNA, we cloned
      the bacterial selection marker gene encoding neomycin phosphotransferase (neo)
      into the plasmid backbone of the vector, but outside of the provirus, resulting
      in efficient selection of transfected packaging cells and generation of packaged
      virus which lacks the neo gene. This novel approach generates greater numbers of
      high infectious titer producing clones, after selection in G418 media, than does
      a co-transfection approach, due to integration of higher construct copy numbers
      per cell. No transmission of the selection marker gene to target cells was
      observed following retroviral transduction. Thus, our strategy eliminates the
      adverse consequences of a selection-based method, while diminishing the burden of
      identification of packaging cells transfected with vectors devoid of selectable
      markers.

PMID- 15158070
TI  - Detection and quantitation of HBV DNA in the WHO International Standard for HIV-1
      RNA (NIBSC code: 97/656).
AB  - Nucleic-acid amplification technology (NAT) assays have been implemented for HCV
      and HIV-1 in the United States, and many parts of Europe, Australia and Asia.
      Nucleic acid detection assays utilize many different technologies, and the WHO
      International Standards for nucleic acid tests are widely used to compare them.
      Currently, several laboratories are developing an assay for simultaneous
      detection of HCV RNA, HIV-1 RNA and HBV DNA. In the course of such development it
      was observed that the WHO International Standard for HIV-1 RNA (97/656) was
      positive for HBV DNA. In this report we confirm the presence of HBV DNA in the
      HIV-1 international standard through the qualitative Procleix-Ultrio assay.
      Further, using the TaqMan technology, through quantitative Bead Capture-TaqMan
      assay, we report that approximately 1000IU/ml dilution of HIV RNA contains
      approximately 4500IU/ml of HBV DNA.

PMID- 15158071
TI  - Herpes simplex virus genotyping: multiple optional PCR-based RFLP systems and a
      non-isotopic single-strand conformation polymorphism method.
AB  - Polymerase chain reaction (PCR)-based methods for herpes simplex virus (HSV)
      types I/II genotyping are described. These methods are based on the single
      stranded conformation properties of DNA molecules obtained by PCR (PCR-SSCP) and
      restriction fragment analysis of PCR products (PCR-RFLP). With the aim to analyse
      these two genotyping techniques, genomic DNA from the standard viral strains KOS
      and G, and also 79 normal cervical samples were studied for HSV I/II. Sequence
      analysis showed 19 different RFLP possible systems for HSV typing. Five systems
      were used in this study and all led to the expected fragments obtained by
      sequence analysis. PCR-SSCP showed distinct patterns for both viral types and had
      100% of concordance with PCR-RFLP results. The prevalence of herpes simplex virus
      in the normal cervical samples were 21.5% (17 out of 79), the most frequent viral
      type was HSV-2, with a prevalence of 71% (12 out of 17). Both techniques appeared
      suitable for HSV I/II genotyping and are easy to perform in most clinical
      laboratories.

PMID- 15158072
TI  - The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total
      rhombencephalic neurons and prevents the reduction of fetal serotonin neurons.
AB  - Previously, this laboratory showed that in utero and in vitro ethanol exposure
      significantly reduces developing serotonin (5-HT) neurons and that treatment with
      a 5-HT1A agonist such as buspirone or ipsapirone prevents the ethanol-associated
      loss. The present study investigated whether ethanol decreases fetal
      rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also
      investigated whether ipsapirone prevents the ethanol-associated deficit of fetal
      rhombencephalic neurons by reducing apoptosis. The results of these studies
      strongly suggest that the ethanol-associated reduction in fetal rhombencephalic
      neurons that accompanies both in utero and in vitro exposure to physiological
      concentrations of ethanol is associated with increased apoptosis in these
      neurons. A physiological concentration of ethanol (i.e., 50 mM) increases
      apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons.
      It also appears that the 5-HT1A agonist ipsapirone provides neuroprotection to
      these neurons by reducing apoptosis. Another mechanism by which ethanol
      associated apoptosis can be blocked is by including serum proteins in the media
      at a concentration of 1% or higher; this concentration of serum proteins is high
      in comparison to the protein concentration in cerebrospinal fluid.

PMID- 15158073
TI  - Sensory deficits in mice hypomorphic for a mammalian homologue of unc-53.
AB  - The migration of cells and the extension of cellular processes along pathways to
      their defined destinations are crucial in the development of higher organisms.
      Caenorhabditis elegans unc-53 plays an important role in cell migration and the
      outgrowth of cellular processes such as axons. To gain further insight into the
      biological function of unc53H2, a recently identified mammalian homologue of unc
      53, we have generated mice carrying a mutation of unc53H2 and provide evidence
      that unc53H2 is involved in neuronal development and, more specifically, the
      development of different sensory systems. The unc53H2 hypomorphic mouse showed a
      general impaired acuity of several sensory systems (olfactory, auditory, visual
      and pain sensation) which in case of the visual system was corroborated by the
      morphological observation of hypoplasia of the optic nerve. We hypothesize that
      in analogy with its C. elegans homologue, unc53H2 may play a role in the
      processes of cellular outgrowth and migration.

PMID- 15158074
TI  - Adolescent enrichment partially reverses the social isolation syndrome.
AB  - Early environmental experience produces profound neural and behavioural effects.
      For example, animals reared in isolation show increased anxiety, neophobia, and
      poorer performance in learning and spatial memory tasks. We investigated whether
      later enrichment reverses some or all of the deficits induced by isolation
      rearing. Eighty-four male Long-Evans rats (21 days old) were reared under
      different conditions: enriched (group housed with toys), isolated (one rat/cage),
      standard (two rats/cage), isolated-enriched, enriched-isolated, isolated
      standard, or enriched-standard. In the latter four conditions, animals were
      housed in the first environment until adolescence (66 days). Following the 90-day
      rearing period, all animals were assessed in a battery of behavioural tests and
      cortical thickness was measured postmortem. Isolation rearing led to significant
      differences in behavioural tests measuring anxiety, spatial learning, and
      locomotor activity; switching the rearing condition partially reversed these
      changes. Rearing condition did not affect pain thresholds in the tail flick test
      or aversive associative learning in the conditioned taste aversion test. Enriched
      rats had the thickest cortex; isolated rats the thinnest. None of the switch
      groups differed significantly from standard-reared rats in this measure. Taken
      together, these results provide novel and interesting information regarding the
      effects of pre- or post-adolescent enrichment experience on behavioural and
      neural expression of the social isolation syndrome.

PMID- 15158075
TI  - Vitamin E amelioration of ethanol neurotoxicity involves modulation of apoptotis
      related protein levels in neonatal rat cerebellar granule cells.
AB  - Developmental ethanol exposure leads to a variety of abnormalities in the central
      nervous system (CNS). Mechanisms proposed as underlying these effects include
      alterations of protective antioxidant support, increased generation of harmful
      free radicals, and altered expression of apoptosis-related proteins. In prior
      studies, exogenous antioxidant application has been found to reduce ethanol
      neurotoxicity, but the mechanisms by which this protection is afforded have not
      been defined. This study was designed to investigate the interactions between
      ethanol and the antioxidant vitamin E (alpha-tocopherol), with respect to
      neuronal survival and levels of proteins related to the Bcl-2 survival-regulatory
      gene family. Neonatal rat cerebellar granule cell cultures were used as a model
      system. It was found that ethanol significantly impaired neuronal survival in
      these preparations, and that survival in the presence of ethanol was enhanced by
      inclusion of vitamin E in the culture medium. This elevated survival was
      paralleled by increased levels of anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl,
      activated Akt kinase), and concurrent downregulation of pro-apoptotic proteins
      (e.g., Bcl-xs). These results suggest that such alterations may represent an
      important mechanism whereby antioxidants protect against the neurotoxic effects
      of ethanol in the developing CNS. The possible manner by which these changes are
      effected are considered.

PMID- 15158076
TI  - Transgenic mice ectopically expressing HOXA5 in the dorsal spinal cord show
      structural defects of the cervical spinal cord along with sensory and motor
      defects of the forelimb.
AB  - Mutation of murine Hoxa5 has shown that HOXA5 controls lung, gastrointestinal
      tract and vertebrae development. Hoxa5 is also expressed in the spinal cord, yet
      no central nervous system phenotype has been described in Hoxa5 knockouts. To
      identify the role of Hoxa5 in spinal cord development, we developed transgenic
      mice that express HOXA5 in the dorsal spinal cord in the brachial region. Using
      HOXA5-specific antibodies, we show this expression pattern is ectopic as the
      endogenous protein is expressed only in the ventral spinal cord at this anterio
      posterior level. This transgenic line (Hoxa5SV2) also displays forelimb-specific
      motor and sensory defects. Hoxa5SV2 transgenic mice cannot support their body
      weight in a forelimb hang, and forelimb strength is decreased. However, Rotarod
      performance was not impaired in Hoxa5SV2 mice. Hoxa5SV2 mice also show a delayed
      forelimb response to noxious heat, although hindlimb response time was normal.
      Administration of an analgesic significantly reduced the hang test defect and
      decreased the transgene effect on forelimb strength, indicating that pain
      pathways may be affected. The morphology of transgenic cervical (but not lumbar)
      spinal cord is highly aberrant. Nissl staining indicates superficial laminae of
      the dorsal horn are severely disrupted. The distribution of cells and axons
      immunoreactive for substance P, neurokinin-B, and their primary receptors were
      aberrant only in transgenic cervical spinal cord. Further, we see increased
      levels of apoptosis in transgenic spinal cord at embryonic day 13.5. Our evidence
      suggests apoptosis due to HOXA5 misexpression is a major cause of loss of
      superficial lamina cells in Hoxa5SV2 mice.

PMID- 15158077
TI  - Prenatal alteration and distribution of the GABA(B1) and GABA(B2) receptor
      subunit mRNAs during rat central nervous system development.
AB  - The prenatal developmental expression changes and distribution of the gamma
      aminobutyric acid (GABA)(B1) and GABA(B2) receptor subunit were investigated
      using in situ hybridization and RNase protection assay (RPA). We defined a
      different expression pattern of GABA(B1) subunit mRNA to that of GABA(B2)
      subunit. GABA(B1) subunit mRNA signals were moderately expressed in the cerebral
      cortex neuroepithelium of discrete brain regions on gestational day (GD) 11.5 and
      12.5 and were highly expressed in the brain and spinal cord on GD 13.5 and 15.5.
      However, GABA(B2) subunit mRNAs were not detected on GD 11.5 and 12.5 and were
      first weakly detected on GD 13.5. On GD 15.5, 17.5, and 19.5, these subunit mRNAs
      were found in the retina, hippocampus, cerebral cortex, spinal cord, and
      cerebellum area. On GD 19.5 and 21.5, these subunits mRNA signals increased in
      the cerebral cortex, hippocampus, thalamus, and cerebellum, but decreased in the
      spinal cord, spinal ganglion, and midbrain, reaching similar levels to that of
      the adult brain. On GD 21.5, these subunit mRNAs were similarly expressed in
      almost all brain areas with a higher expression level of GABA(B1) subunit mRNA
      than GABA(B2) subunit mRNA. Our results found that GABA(B1) and GABA(B2) subunit
      mRNAs showed different expression patterns, with the GABA(B1) subunit expressed
      earlier and higher. We suggest that GABA(B1) and GABA(B2) subunits might have a
      role in the fetal brain during the gestational period for pre- and post
      synaptogenesis, proliferation, differentiation, and neuronal maturation, and
      GABA(B1) subunit may be more important than GABA(B2) subunit during rat prenatal
      development.

PMID- 15158078
TI  - Selective serotonin reuptake inhibitor disrupts organization of thalamocortical
      somatosensory barrels during development.
AB  - To further investigate the role of the transiently expressed serotonin (5-HT)
      transporter (5-HTT) in the development of thalamic fibers projecting to cortical
      barrels and the potential developmental changes in neuronal circuitry caused by a
      selective serotonin reuptake inhibitor (SSRI), paroxetine (5 mg/kg, twice daily,
      s.c.) or saline was administered to rat pups from postnatal day 0 (P0) to P8.
      Pups were perfused on P8 for 5-HT immunostaining (-im) to confirm the 5-HT uptake
      blockade, and 5-HTT-im and phospholipase C-beta1 (PLC-beta1)-im to label the
      thalamic afferents to barrels and barrel cells respectively. Paroxetine treatment
      completely blocked 5-HT uptake into the thalamocortical fibers as indicated by
      the negative 5-HT-im in cortical barrel areas. Organization of thalamic afferents
      to barrels, indicated by 5-HTT-im or PLC-beta1, was altered in paroxetine-treated
      pups in the following manners: (1) segregation of thalamocortical fibers was
      partially disrupted and thalamocortical fibers corresponding to anterior snouts
      and row A mystacial vibrissae were fused; (2) sizes of the unfused
      thalamocortical fiber patches related to the long caudal vibrissae in rows B, C,
      D and E were significantly decreased without changes in the brain weights and
      cortical areas representing these vibrissae; and (3) thalamocortical fibers
      corresponding to C4 and D4 vibrissae tended to be closer to each other along the
      arc while the relative positions of thalamocortical fibers related to the rest of
      the vibrissae were normal. Our study demonstrated that 5-HTT plays an important
      role in the refinement, but not the formation, of barrel-like clusters of
      thalamocortical fibers and that the development of neural circuitry in rodent
      somatosensory cortex was affected by exposure to a SSRI during thalamocortical
      synaptic formation.

PMID- 15158079
TI  - Transient dopamine synthesis modulation in prefrontal cortex: in vitro studies.
AB  - The present study provides further evidence for transient D1 autoreceptor-like
      synthesis modulation in prefrontal cortex, but not striatum, of developing rats.
      DOPA accumulation was attenuated in a concentration-dependent manner in slices
      from the prefrontal cortex and striatum at 15 days of age by the partial D1
      agonist SKF 38393 (0.01-10 microM) and the full D1 agonist SKF-81297 (0.01-10
      microM) following NSD-1015; the response was no longer apparent by 40 days. Both
      agonists had greater potency in prefrontal cortex than striatum, and SKF-81297
      exerted greater maximal inhibitory effects than SKF-38393. The inhibitory effects
      of both agonists were antagonized by pre-incubation with the D1 antagonist SCH
      23390 in cortex, but not in striatum.

PMID- 15158080
TI  - Developmental expression of Ca(v)1.3 (alpha1d) calcium channels in the mouse
      inner ear.
AB  - Voltage-gated calcium channels are important for neurotransmission at the level
      of inner hair cells (IHCs) and outer hair cells (OHCs). These channels open when
      mechanical stimulation depolarises the hair cell membrane and the resulting
      calcium influx triggers neurotransmitter release. Voltage-gated calcium channels
      expressed in hair cells are known to be of the L-type with a predominance of the
      Ca(v)1.3 subunit. The present study describes the developmental expression of the
      Ca(v)1.3 protein in the cochlea and the vestibular system using
      immunohistochemical technique. In the adult organ of Corti (OC), Ca(v)1.3 was
      localized in both sensory and non-sensory cells with a more intense expression in
      IHCs and Deiters cells when compared to OHCs. In both hair cell types,
      immunoreactivity was observed in the apical pole, basolateral membrane and at the
      basal pole (synaptic zone). Similar results were obtained in the vestibular
      organs. During development, Ca(v)1.3 immunoreactivity was observed in the cochlea
      as early as embryonic day 15, with expression increasing at birth. At these early
      stages of cochlear development, Ca(v)1.3 was expressed in all cell types
      surrounding the scala media. In the OC, the labeling was observed in IHCs, OHCs
      and supporting cells. The Ca(v)1.3 expression reached an adult-like pattern by
      the end of the second postnatal week. The present findings suggested that, in
      addition to their implication in hair cells synaptic transmission, Ca(v)1.3
      calcium channels also play an important role in vesicle recycling and transport,
      as suggested by their extrasynaptic location at the apical pole of the hair
      cells. The Ca(v)1.3 channels in Deiters cells could participate in active calcium
      induced changes in micromechanics of these supporting cells. An early expression
      during development suggested that these calcium channels are in addition
      important in the development of the cochlear and vestibular sensory epithelium.

PMID- 15158081
TI  - Morphological development and maturation of the GABAergic synapses in the mouse
      cerebellar granular layer.
AB  - In the adult central nervous system (CNS), gamma-amino butyric acid (GABA) is a
      predominant inhibitory neurotransmitter, which regulates glutamatergic activity.
      Recent studies have revealed that GABA serves as an excitatory transmitter in the
      immature CNS, and is involved in brain morphogenesis. To elucidate how GABA
      exerts its effect on immature neurons and how GABAergic synapses are formed, we
      examined both development of pre- and post-synaptic elements of the GABAergic
      synapses formed between granule and Golgi cells in the mouse cerebellar granular
      layer. Immunohistochemistry for glutamic acid decarboxylase (GAD) demonstrated
      that GABA was localized throughout the Golgi cells before postnatal day 7 (P7),
      and became confined to the axon terminals during the second postnatal week.
      Electron microscopic analysis demonstrated that GABAergic synapses were clearly
      detected at P10. In situ hybridization and immunohistochemistry for the GABA(A)
      receptor alpha1 and alpha6 subunits, which are mainly involved in inhibitory
      synaptic transmission, demonstrated that both subunits appeared at P7.
      Distribution of both subunits expanded in the granular layer with special
      reference to the development of GABAergic synapses. Furthermore, the majority of
      the subunits accumulated adjacent to the GABAergic terminals. These results
      suggested that in the granular layer, GABA might be non-synaptically secreted
      from Golgi cell axons and dendrites during the first postnatal week. From the
      second postnatal week, GABA is synaptically released and begins to mediate
      inhibitory transmission. Furthermore, it was suggested that GABAergic innervation
      could initiate expression and trafficking of the GABA(A) receptors containing the
      alpha1 and alpha6 subunits.

PMID- 15158082
TI  - Neuroprotective effects of estradiol in newborn female rat hippocampus.
AB  - Perinatal brain injury, consequent to hypoxic/ischemic events, is associated with
      the release of excess excitatory neurotransmitters, including glutamate. We have
      previously shown that administration of a glutamate receptor agonist, kainic acid
      (KA), to postnatal day 0 (PN0) and PN1 rats results in damage selective to the
      dentate gyrus of females. Pretreatment with the gonadal steroid estradiol
      prevents KA-induced damage to the female dentate gyrus. To begin to elucidate the
      cellular mechanism of the neuroprotective effects of estradiol in neonatal
      females, we have employed the estrogen receptor antagonists Tamoxifen and ICI
      182,780 in vivo and in vitro, respectively. Peripheral administration of
      Tamoxifen, which crosses the blood-brain barrier, prevented estradiol-mediated
      neuroprotection against KA-induced damage in the dentate gyrus. The highly
      selective estrogen receptor antagonist ICI 182,780, which does not penetrate into
      the brain from the periphery, also prevented estradiol's protective effects on KA
      induced cell death in cultured hippocampal neurons but only late in the time
      course of injury. The data suggest that the neuroprotection afforded by estradiol
      against KA-induced injury in the female is estrogen receptor mediated but may
      include an additional mechanism that is not antagonized at the receptor.

PMID- 15158083
TI  - Spatial, temporal, and cellular distribution of the activated extracellular
      signal regulated kinases 1 and 2 in the developing and mature rat cerebellum.
AB  - The extracellular signal regulated kinases 1 and 2 (ERK1/2) are important members
      of an intracellular signaling cascade that is involved in many aspects of the
      cellular physiology and development of neurons and glia. ERK1/2 are expressed in
      many brain regions including the cerebellum; however, their role during
      cerebellar development is poorly understood. Immunohistochemical approaches using
      phosphorylation-state specific antiserum that recognizes only the activated
      ERK1/2 (pERK) were used to characterize the spatial and temporal patterns of
      activated-ERK in the developing and adult rat cerebellum. The distribution and
      cell type-specificity of pERK-immunoreactivity (IR) followed an age-related
      pattern, with the density of pERK-IR Purkinje cells decreasing between P6 and P15
      and increasing at later times. Immunopositive granule cell neurons increased from
      P6 to P12, became decreased during much of late postnatal cerebellar development,
      and absent in adults. Co-localization of pERK with glial fibrillary acidic
      protein or the neuronal marker beta-tubulin revealed that activated ERK is
      present in maturing Purkinje and granule cells, and the soma of Bergmann glia on
      P4, P10 and P15; pERK was detected in astrocytes on P10 and P15. Associated with
      weaning, there was a general increase in activated-ERK in all cell types on P22.
      In adults, pERK-IR was confined to the Purkinje cell layer and scattered cells in
      the corpus medullare. In summary, a high degree of developmental plasticity was
      observed in the spatiotemporal distribution of cerebellar pERK-IR suggesting that
      the ERK-pathway plays a dynamic role in regulating neuronal and glial migration,
      proliferation and differentiation in the developing cerebellum. In the mature
      cerebellum, ERK signaling may also mediate postsynaptic information processing.

PMID- 15158084
TI  - The proximal 2-kb of the Hoxa3 promoter directs gene expression in distinct
      branchial compartments and cranial ganglia.
AB  - Developing structures such as hindbrain, neural crest cells or spinal cord
      express Hoxa3. Here, we have investigated the regulatory role of a 2-kb fragment
      spanning the proximal promoter of Hoxa3 by a reporter-based approach in mice. We
      show that this fragment promotes reporter activity in ganglionic and branchial
      compartments known to express Hoxa3 but for which no cis-regulatory elements have
      been identified so far. We also show that the 2-kb promoter fragment is active in
      rhombomere 4 and in the ganglion of the cranial nerve complex VII/VIII that are
      devoid of Hoxa3 expression.

PMID- 15158085
TI  - Apoptosis in acute leukemia.
AB  - In leukemias and malignant tumors the balance between apoptosis and cell
      proliferation is dysregulated. This review deals with the apoptosis in acute
      leukemia. There are several publications about the molecular basis of decreased
      apoptosis in acute lymphoid leukemia (ALL) and AML. However, there have been
      contradictory results. Different results are published about the correlation of
      the spontaneous and induced apoptosis in leukemia with prognosis. The potential
      causes of these contradictions are discussed.

PMID- 15158086
TI  - Ajoene (natural garlic compound): a new anti-leukaemia agent for AML therapy.
AB  - The reputation of garlic (Allium sativum) as an effective remedy for tumours
      extends back to the Egyptian Codex Ebers of 1550 b.c. Several garlic compounds
      including allicin and its corresponding sulfide inhibit the proliferation and
      induce apoptosis of several human non-leukaemia malignant cells including breast,
      bladder, colorectal, hepatic, prostate cancer, lymphoma and skin tumour cell
      lines. Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) is a garlic-derived
      compound produced most efficiently from pure allicin and has the advantage of a
      greater chemical stability than allicin. Several clinical trials and in vitro
      studies of ajoene have demonstrated its best-known anti-thrombosis, anti
      microbial and cholesterol lowering activities. Recently, topic application of
      ajoene has produced significant clinical response in patients with skin basal
      cell carcinoma. Ajoene was shown to inhibit proliferation and induce apoptosis of
      several human leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM
      1. Also, ajoene induces 30% apoptosis in myeloblasts from chronic myeloid
      leukaemia patient in blast crisis. More significantly, ajoene profoundly enhanced
      the apoptotic effect of the two chemotherapeutic drugs: cytarabine and
      fludarabine in human CD34-positive resistant myeloid leukaemia cells through
      enhancing their bcl-2 inhibitory and caspase-3 activation activities. The two key
      anti-leukaemia biological actions of ajoene were the inhibition of proliferation
      and the induction of apoptosis. Studies have shown the anti-proliferation
      activity of ajoene to be associated with a block in the G2/M phase of cell cycle
      in human myeloid leukaemia cells. The apoptosis inducing activity of ajoene is
      via the mitochondria-dependent caspase cascade through a significant reduction of
      the anti-apoptotic bcl-2 that results in release of cytochrome c and the
      activation of caspase-3. Since acute myeloid leukaemia (AML) is a heterogeneous
      malignant disease in which disease progression at the level of CD34-positive
      cells has a major impact on resistance to chemotherapy and relapse and the
      inability to undergo apoptosis is a crucial mechanism of multi-drug resistance in
      AML patients. The recent findings of the potent enhancing activity of ajoene on
      chemotherapy-induced apoptosis in CD34-positive resistant human myeloid leukaemia
      cells suggest a novel promising role for the treatment of refractory and/or
      relapsed AML patients as well as elderly AML patients. Further studies are
      warranted to evaluate similar enhancing effect for ajoene in blast cells from AML
      patients in primary cultures before its introduction in pilot clinical study.

PMID- 15158087
TI  - Is "aberrant" antigen expression in acute leukemia always an abnormal finding?

PMID- 15158088
TI  - VEGF and myeloid leukemias.
AB  - Vascular endothelial growth factor and vascular endothelial growth factor
      receptors participate in the growth and survival of myeloid leukemic progenitors.
      With the development of multiple anti-angiogenic agents, there is potential that
      some of these novel agents will have anti-leukemic activity. Since these agents
      work by mechanisms distinct from current cytotoxic chemotherapies, they may be
      useful both in chemoresistant leukemia patients and in combinations to improve
      remission rates and remission durations.

PMID- 15158089
TI  - Effects of SU5416, a small molecule tyrosine kinase receptor inhibitor, on FLT3
      expression and phosphorylation in patients with refractory acute myeloid
      leukemia.
AB  - Acute myeloid leukemia (AML) is associated with dysregulated hematopoietic cell
      proliferation and increased bone marrow angiogenesis, each regulated by signaling
      through receptor tyrosine kinases (RTKs). SU5416 is a small molecule inhibitor of
      VEGF receptors, c-kit and FLT3 and therefore provides a novel opportunity to
      target both angiogenesis and proliferation in AML. SU5416 was assessed in a phase
      II hematological malignancy trial in the US, where partial responses were
      observed in two of 33 patients. Since AML provides a unique platform to evaluate
      mechanism of action of small molecule inhibitors, investigation of the effect of
      SU5416 on FLT3 expression and phosphorylation in blood and bone marrow was an
      additional focus of this trial. Phosphorylated FLT3 was detected by
      immunoprecipitation/Western analysis in peripheral blood samples from 17 of 22
      patients, and seven exhibited strong inhibition of phosphorylation immediately
      following a 1h SU5416 infusion, demonstrating that SU5416 can modulate RTK
      phosphorylation in humans. Although no clear correlation with clinical response
      was observed, analysis of patient plasma drug levels suggested that a threshold
      SU5416 concentration of 15 microM was associated with FLT3 inhibition. This
      observation was supported by data from an ex vivo model where AML cells were
      spiked into human blood, established to mimic the clinical setting and enable
      more rigorous analysis of effect of SU5416. In addition, FLT3 protein levels were
      downregulated in patient bone marrow samples, analyzed by an RIA assay. To
      identify putative predictors of response, patient plasma was analyzed for levels
      of secreted ligands of SU5416 targets; SCF and FLT3 ligand. Baseline levels of
      SCF in patients with stable or progressive disease were significantly higher than
      those in normal donors, whereas FLT3 ligand levels in patients who exhibited
      progressive disease were significantly lower than those in normal donors. The
      translational and clinical analyses described in this report provide some
      insights into the mechanism and duration of action of SU5416.

PMID- 15158091
TI  - Real-time quantification of TEL-AML1 fusion transcripts for MRD detection in
      relapsed childhood acute lymphoblastic leukaemia. Comparison with antigen
      receptor-based MRD quantification methods.
AB  - Response to therapy of ALL assessed by molecular methods has been proved to be a
      predictor of outcome. Alternatively to established but very labour-intensive DNA
      based PCR-techniques the TEL-AML1 fusion transcript can serve as a marker for MRD
      monitoring. MRD quantification using TEL-AML1 is of particular interest if the
      results are directly comparable to data obtained by established DNA-based assays.
      Investigation of the potential of MRD monitoring using LightCycler technology for
      TEL-AML1 real-time quantification and comparison to results from established DNA
      based MRD assays revealed corresponding results. Accordingly, TEL-AML1 MRD
      quantification is a sensitive, specific and rapid method that can supplement
      clone-specific MRD detection.

PMID- 15158090
TI  - Simultaneous expression of CD13, CD22 and CD25 is related to the expression of Fc
      epsilon R1 in non-lymphoid leukemia.
AB  - Like CD19 or CD56, CD22 in non-lymphoid leukemia has been considered an
      aberrantly expressed antigen. CD22 had been believed to be restricted to B
      lymphoid, however, it was also found to be expressed in human basophils. Mature
      basophils are unique granulocytes expressing CD13, CD22 and CD25. To estimate
      whether the expression of CD22 in non-lymphoid leukemia is aberrant or related to
      basophilic character, we analyzed 108 patients with primary and secondary
      leukemia. Among non-lymphoid leukemias, surface CD22 expression was more
      frequently observed in peroxidase-negative AML and secondary leukemia, and was
      usually observed simultaneously with CD13 and CD25. Samples obtained from 17
      cases were further analyzed, and all the Fc epsilon R1-positive cases were
      observed in peroxidase-negative AML and secondary non-lymphoid leukemia, and
      mostly expressed CD13, CD22 and CD25. Therefore, surface CD22 expression in non
      lymphoid leukemia was thought to relate to basophilic phenotype in some cases.
      Like CD22, some of the so-called aberrantly expressed antigens may not actually
      be aberrant, but are expressed in a stage of differentiation and maturation of
      progenitors. Moreover, CD22 may be one of target molecules for treatment of CD22
      positive, poorly prognostic leukemia.

PMID- 15158092
TI  - Telomerase activity is not a prognostic factor in chronic lymphocytic leukemia.
AB  - We measured telomerase activity (TA) in bone marrow samples from 214 patients
      with CLL and correlated it with patients' characteristics and survival. In >50%
      of cases (126/214; 59%) no detectable TA was found. There was no difference in TA
      between previously treated (n = 153) and untreated (n = 61) patients (P = 0.4),
      or patients with various Rai (0-IV) stages (P = 0.85). TA correlated
      significantly with white blood cell and lymphocyte count (P = 0.02 and 0.01,
      respectively) but not with bone marrow cellularity, beta2-microglobulin (beta2M),
      or other patient characteristics. Patients who had no TA had slightly lower
      beta2M and lower lymphocyte counts (P = 0.5 and 0.04, respectively) as compared
      with patients with detectable TA. However, there was no correlation between TA
      and survival. This data suggests that TA may not play a significant role in the
      clinical behavior of CLL.

PMID- 15158093
TI  - Population-based study of lymphoma in Germany: rationale, study design and first
      results.
AB  - A multi-centre, population-based case-control study of lymphoma among adults was
      conducted in Germany from 1999-2003. The study comprised 700 incident cases
      (Hodgkin lymphomas and non Hodgkin's lymphoma, NHL) in the age range 18-80 years
      and 700 age-, sex- and area-matched controls obtained from population registries.
      Diagnosis was based on the REAL/WHO classification. Information on demographic
      characteristics, lifestyle, medical history and occupation was obtained by in
      person interviews. Each participant was asked for a 24 ml blood sample. First
      results are focused on basic demographic characteristics, contact to animals,
      childhood diseases and vaccinations. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated using conditional logistic regression. The ORs for
      lymphoma were decreased for exposure to sheep and goats (OR = 0.7; 95% CI = 0.5
      0.9), for rabbits and hare (OR = 0.7; 95% CI = 0.5-0.9), measles infection (OR =
      0.6; 95% CI = 0.5-0.9), Bordetella pertussis infection (OR = 0.7; 95% CI = 0.6
      0.95), and tetanus vaccination (OR = 0.5; 95% CI = 0.3-0.9). Increased risk of
      lymphoma was associated with exposure to cattle (OR = 1.3; 95% CI = 1.03-1.7) and
      immunization for tuberculosis (OR = 1.5; 95% CI = 0.997-2.4). The results of this
      study are partly consistent with the hygiene hypothesis. The inconsistencies of
      some of the findings with an explanation by the Th1/Th2 paradigm, however,
      warrant further research and may indicate that broader explanatory concepts are
      needed.

PMID- 15158095
TI  - Stromal cell protection of B-lineage acute lymphoblastic leukemic cells during
      chemotherapy requires active Akt.
AB  - Several studies document ALL cell response to survival signals from bone marrow
      stromal cells. The current study suggests a requirement for active Akt in ALL
      cells for optimal stromal cell protection during chemotherapy. ALL cells
      expressing dominant negative Akt were not efficiently rescued from Ara-C or
      etoposide-induced apoptosis by stromal cell co-culture. In addition, inhibition
      of ALL cell PI-3 kinase activity diminished stromal cells support of tumor cells
      during treatment. ALL cell lines co-cultured with bone marrow stromal cells
      during chemotherapy maintained higher levels of phosphorylated Akt protein and
      reduced PP2A activity when compared to ALL cells treated in medium alone.
      Chemotherapy-induced PARP and Bcl-2 cleavage was reduced in ALL cells cultured
      with a stromal cell layer compared to tumor cells exposed to drug in medium
      alone. However, interaction with stromal cells was not able to efficiently block
      treatment-induced PARP or Bcl-2 cleavage in leukemic cells with blunted Akt
      activity. These data suggest a pivotal role for Akt in mediating stromal cell
      regulation of ALL cell apoptosis.

PMID- 15158094
TI  - Metabolic response patterns of nucleotides in B-cell chronic lymphocytic
      leukaemias to cladribine, fludarabine and deoxycoformycin.
AB  - Nucleotides (NTPs and dNTPs) have been measured in patient-derived chronic
      lymphocytic leukaemia (CLL) cells stimulated with TPA plus ionomycin and then
      exposed to cladribine, fludarabine or deoxycoformycin (1 microM, 16 h). dNTPs
      were not measurable in 10(8) unstimulated CLL cells which are quiescent. Time
      dependent changes in nucleotides in CLL cells showed that the mechanism of action
      changed as the drug triphosphate accumulated. dCf induced substantial
      accumulation of dATP in CLL cells in culture, and similar levels of dATP in the
      same patient during subsequent treatment with dCf. Determination of "metabolic
      response patterns" of nucleotides in CLL cells treated with drugs might
      distinguish patients with susceptible and refractory CLL prior to chemotherapy.

PMID- 15158096
TI  - DNA microarray screening of differential gene expression in bone marrow samples
      from AML, non-AML patients and AML cell lines.
AB  - This study used cDNA microarray technology to compare gene expression profiles in
      acute myeloblastic leukaemia (AML) with cDNA dot-blot and real time PCR analysis
      of cDNA transcripts to confirm array data. Patient AML marrow samples and AML
      cell lines were compared with normal/non-AML samples. Screening revealed five
      particular genes to be significantly differentially expressed across the sample
      groups. The migration-inhibitory factor-related-proteins 8 and 14 (MRP-8 and MRP
      14) genes, the products of which inhibit cell migration and differentiation were
      the most highly expressed in non-malignant cells. The high-mobility-group-protein
      gene (HMG-1) was up regulated in leukaemic samples and cell lines, which may be
      associated with aggressive disease. Also upregulated in malignant samples were
      genes encoding c-myc and glutathione-S-transferase pi (GSTP), the latter
      implicated in chemotherapy resistance. Faulty expression of such genes may
      contribute to the pathogenesis of AML and resistance to treatment.

PMID- 15158098
TI  - Effect of antisense VEGF cDNA transfection on the growth of chronic myeloid
      leukemia K562 cells in vitro and in nude mice.
AB  - To further elucidate the role of vascular endothelial growth factor (VEGF) in the
      pathogenesis of chronic myeloid leukemia (CML), we transfected K562 cells with a
      VEGF(121)cDNA sense vector (S), an antisense (AS) vector or vector (V) alone. The
      growth of transfected cells was investigated by MTT and colony-formation assays,
      and apoptosis was measured by flow cytometry (FCM) of Annexin-V-FITC/PI dual
      labeled cells. Transfected cells were subcutaneously transplanted into nude mice
      and the microvessel density (MVD) of tumor masses was determined by vWF
      immunohistochemistry staining. We tested the supernatant of different transfected
      K562 cells against human bone marrow endothelial cells (BMECs), and examined the
      synergic effects of antisense VEGF(121)cDNA and IFNalpha or STI571 on the
      proliferation and apoptosis of K562 cells. We found that K562/AS transfectants
      exhibited a 49% reduction in VEGF secretion, whereas K562/S transfectants
      exhibited a 3-fold increase in VEGF secretion, all in comparison to the vector
      controls. K562 cells transfected with antisense VEGF(121)cDNA showed growth
      retardation in vitro. In transplanted nude mice in vivo, transfection of
      implanted cells with antisense VEGF(121)cDNA resulted in decreased tumor MVD, and
      increased apoptosis in the presence of IFNalpha. Taken together, these results
      suggest that VEGF may be involved in the pathogenesis of CML through autocrine
      and paracrine mechanisms, and that anti-VEGF therapy alone or in combination with
      conventional treatment may be beneficial for CML patients.

PMID- 15158097
TI  - Ribosomal p70S6K basal activity increases upon induction of differentiation of
      myelomonocytic leukemic cell lines HL60, AML14 and MPD.
AB  - The role of ribosomal p70S6K in the cell cycle has been studied extensively, and
      it is known that this enzyme is crucial for cell advancement through G(1).
      Conversely, the participation of p70S6K in cell differentiation is not well
      understood. We have studied the response of p70S6K to the cytokine granulocyte
      macrophage colony stimulating factor (GM-CSF) in three differentiation-capable
      leukemic cell lines (MPD, AML-14 and HL-60) and in normal mature neutrophils.
      Immature leukemic cells starved for 16 h showed a robust ( approximately 3.5-fold
      over controls) p70S6K phosphorylation on T(421)/S(424) residues in response to an
      acute (5 min) 10 nM GM-CSF stimulation. On the other hand, cells that had been
      induced to differentiate and express granulocytic phenotypes, showed an increased
      ( approximately 6-fold) basal level of p70S6K T(421)/S(424) phosphorylation over
      immature cells, as well as an increased baseline tyrosyl phosphorylation of the
      GM-CSF receptor beta subunit (GM-CSF.Rbeta). However, the differentiated cells
      displayed a weak ( approximately 1.4-fold over controls) response to GM-CSF even
      at prolonged incubation times (20 min). In vitro p70S6K enzymatic activity
      paralleled p70S6K T(421)/S(424) phosphorylation in both high basal, unstimulated,
      levels in immature cells and a low degree of response to GM-CSF. Lastly,
      peripheral blood mature neutrophils had low basal GM-CSF.Rbeta and p70S6K
      activity, with both parameters being robustly stimulated following addition of GM
      CSF, a situation in contrast with the cell lines, indicative perhaps of their
      incomplete terminal differentiation. In summary, these findings show the increase
      in basal phosphorylation of p70S6K upon granulocytic differentiation of myeloid
      leukemic cells and their responses to GM-CSF that are closely paralleled with
      tyrosyl phosphorylation of its receptor, and help in pointing to specific cell
      signaling molecules that are different in leukemic blasts from normal leukocytes.

PMID- 15158099
TI  - Imatinib-mesylate for all patients with hypereosinophilic syndrome?

PMID- 15158101
TI  - Chronic disease control in public health practice: looking back and moving
      forward.

PMID- 15158102
TI  - Patient self-management: a key to effectiveness and efficiency in care of chronic
      disease.

PMID- 15158103
TI  - Integrating population smoking cessation policies and programs.

PMID- 15158104
TI  - Addressing the chronic disease burden with tobacco control programs.

PMID- 15158105
TI  - The growing burden of chronic disease in America.

PMID- 15158106
TI  - From research to policy: Targeting the primary prevention of childhood lead
      poisoning.
AB  - Public policy can be an effective method of promoting public health and
      preventing disease in a population. The proposing and passing of a municipal
      ordinance regulating power-sanding of leaded paint in New Orleans is a policy
      level intervention that implements a primary prevention measure to address a
      community-wide risk. The process of achieving policy change involves defining the
      problem and the proposed intervention, integrating the resources of the
      individuals and groups with a stake in the situation, and disseminating
      information to the general public and to legislators. The implementation of the
      ordinance regulating power-sanding in New Orleans is a community-level lead
      poisoning prevention strategy.

PMID- 15158107
TI  - State implementation of the Breast and Cervical Cancer Prevention and Treatment
      Act of 2000: a collaborative effort among government agencies.
AB  - The National Breast and Cervical Cancer Early Detection Program
      (NBCCEDP),administered by the Centers for Disease Control and Prevention through
      grants to states, tribes, and territories, has successfully provided breast and
      cervical cancer screening and diagnostic services to low-income women since 1990.
      On October 24, 2000, Congress passed the Breast and Cervical Cancer Prevention
      and Treatment Act (BCCPTA) authorizing states, if they chose, to provide Medicaid
      coverage for treatment services for women screened under theNBCCEDP. Under
      BCCPTA, uninsured women younger than age 65 who are screened through the NBCCEDP
      and found to have breast or cervical cancer (or precancerous conditions) may gain
      access to Medicaid services for and during their cancer treatment. Implementation
      of the BCCPTA requires collaboration and coordination among many government
      agencies, including the Centers for Disease Control and Prevention, Centers for
      Medicare & Medicaid Services, state Medicaid directors, and directors of state
      and tribal grant programs. This article describes the implementation of the
      program and demonstrates to policy makers that coordinating resources among
      government agencies can facilitate the rapid adoption of public health programs
      as pathways for specific populations to gain access to publicly funded health
      insurance coverage.

PMID- 15158108
TI  - Enabling the nation's schools to help prevent heart disease, stroke, cancer,
      COPD, diabetes, and other serious health problems.
AB  - In the United States, more than 53 million young people attend nearly 120,000
      schools, usually for 13 of their most formative years. Modern school health
      programs--if appropriately designed and implemented--could become one of the most
      efficient means the nation might employ to reduce the establishment of four main
      chronic disease risks: tobacco use, unhealthy eating patterns, inadequate
      physical activity, and obesity. The U.S. Centers for Disease Control and
      Prevention and its partners have developed four integrated strategies to help the
      nation's schools reduce these risks. Participating national, state, and local
      agencies (1) monitor critical health risks among students, and monitor school
      policies and programs to reduce those risks; (2) synthesize and apply research to
      identify, and to provide information about, effective school policies and
      programs; (3) enable state, large city, and national education and health
      agencies to jointly help local schools implement effective policies and programs;
      and (4) evaluate implemented policies and programs to iteratively assess and
      improve their effectiveness.

PMID- 15158109
TI  - The National Tobacco Control Program: focusing on policy to broaden impact.
AB  - Tobacco use is the single most preventable cause of death and disease in the
      United States, causing more than 440,000 premature deaths annually. We can
      dramatically reduce the health and economic burden of tobacco use by employing
      proven tobacco control and prevention strategies. Policy interventions offer the
      greatest opportunity to influence decisions regarding tobacco use at the societal
      level. Tobacco control policy can drive social, environmental, and systems
      changes, and has a substantially greater impact than interventions that target
      individuals. A policy approach engages the larger community and empowers it to
      establish healthy social norms. Health departments, the primary governmental
      institutions charged with protecting the health of the public, play many
      different roles in advancing policy. The National Tobacco Control Program funds
      state health departments to educate the public and decision makers regarding
      evidence-based policy strategies. This article outlines those strategies,
      critical success factors, and challenges associated with policy-based
      interventions.

PMID- 15158110
TI  - Using the Essential Public Health Services as strategic leverage to strengthen
      the public health response to diabetes.
AB  - If current trends continue, health systems will soon be overwhelmed by type 2
      diabetes mellitus. Successful population-based diabetes prevention and control
      efforts require a sound and continually improving infrastructure. In states and
      U.S. territories, the Diabetes Prevention and Control Programs supported by the
      U.S. Centers for Disease Control and Prevention's Division of Diabetes
      Translation serve as a fulcrum for building and refining the infrastructure that
      links diverse and dynamic partners dedicated to increasing the years and quality
      of life and achieving health equity among people with and at risk for diabetes.
      The National Public Health Performance Standards offer a conceptual framework
      that articulates the requisite infrastructure and services provided by an
      interconnected network of intersectoral partners to strengthen the public health
      response to diabetes. These standards associated with the Essential Public Health
      Services are valuable tools to assess the status of the performance of the health
      system's infrastructure to guide improvement. The process of engaging system
      partners in a system-wide assessment informs and leverages cross-sectoral assets
      to improve health outcomes for citizens in communities shouldering the growing
      burden of diabetes.

PMID- 15158111
TI  - Reducing disparities for African Americans with diabetes: progress made by the
      REACH 2010 Charleston and Georgetown Diabetes Coalition.
AB  - Racial and Ethnic Approaches to Community Health (REACH 2010) is a U.S. Centers
      for Disease Control and Prevention demonstration program that responds to the
      U.S. Department of Health and Human Services' goal to eliminate racial and ethnic
      disparities in health status by the year 2010. As part of REACH 2010, community
      projects were funded to develop, implement, and evaluate community action plans
      to improve health care and outcomes for racial and ethnic populations. This
      article describes the program and details the progress of the REACH 2010:
      Charleston and Georgetown Diabetes Coalition in reducing disparities in care.
      Approaches employed by the Coalition included community development, empowerment,
      and education related to diabetes; health systems change associated with access,
      care, and education; and coalition advocacy. Racial disparities were identified
      for 12,000 African Americans with diabetes in this urban/rural South Carolina
      community. After 24 months, significant differences that initially ranged from
      11% to 28% in African Americans (when compared with whites/others) were not
      observed on 270 chart audits for A1C, lipid and kidney testing, eye examinations,
      and blood pressure control. Future efforts will focus on maintaining progress,
      eliminating other disparities, and identifying the contributions of each
      intervention in eliminating racial disparities.

PMID- 15158112
TI  - Physical activity policy and program development: the experience in Finland.
AB  - This article describes the development of sports and physical activity policies
      and programs in Finland during the past 30 years. The past two decades have been
      marked by a shift in emphasis from competitive and elite sports to health
      enhancing physical activity for all, as seen most clearly in two successive
      sports acts and a government resolution. The new, increasingly multisectoral
      policies have led to substantial changes in the public funding of sports
      organizations, services, and construction of sports sites. Furthermore, three
      successive five-year national physical activity promotion programs have been
      launched. As a result, increased and new types of opportunities to participate in
      physical activity have become available, and the infrastructure and networks for
      provision of services have been strengthened. Until the mid 1990s, leisure time
      physical activity increased in Finland, but during the last seven to eight years,
      both leisure time and commuting physical activity have been stable. This finding
      may be an indication of the difficulty to increase physical activity in an
      industrialized country with already relatively high levels of physical activity
      even when systematic, long-term policies and measures are applied.

PMID- 15158113
TI  - Physical Activity Policy Development: a synopsis of the WHO/CDC Consultation,
      September 29 through October 2, 2002, Atlanta, Georgia.
AB  - Physical activity is an important part of the World Health Organization's
      integrated approach to the prevention and control of noncommunicable disease and
      the promotion of health, and, in particular, to the evolving World Health
      Organization Global Strategy on Diet and Physical Activity. To assist in these
      efforts, a joint World Health Organization/Centers for Disease Control and
      Prevention Consultation on Physical Activity Policy Development took place in
      Atlanta, Georgia, from September 29 through October 2, 2002. This article
      summarizes the context and outcomes of the consultation. It also includes
      elaboration of a Comprehensive Physical Activity Policy Framework developed as a
      product of the meeting.

PMID- 15158114
TI  - International physical activity policy development: a commentary.
AB  - Scientific evidence demonstrates, in different degrees for developing and
      developed countries, that physical activity is associated with substantial
      health, economic, and societal benefits. However, for varying environmental,
      social, and individual reasons, people do not tend to engage in the levels of
      physical activity that would be beneficial to them. Environmental and policy
      interventions hold particular promise for promoting physical activity because
      both are designed to influence large groups. Recent multisectoral actions have
      increased the visibility of physical activity promotion and its synergism with
      other important community and national issues. Together, these efforts have
      created an unprecedented opportunity to advance the development of international
      physical activity policy.

PMID- 15158115
TI  - Changes in health behaviors among older Americans, 1990 to 2000.
AB  - OBJECTIVES: The authors used a large population-based survey to examine changes
      from 1990 to 2000 in age distribution by sex and race or ethnicity, to estimate
      both state-specific and national trends in the proportion of older Americans, and
      to examine changes in risk factors and quality-of-life indicators among those
      Americans. METHODS: The Behavioral Risk Factor Surveillance System (BRFSS), a
      cross-sectional telephone survey of adults aged > or =18 years. BRFSS data were
      analyzed for the District of Columbia and all states that participated from 1990
      to 2000. SAS and SUDAAN were used in the analyses to account for the complex
      sampling design. RESULTS: The percentage of Americans aged > or =75 years
      increased 23.0% from 1990 to 2000, with the magnitude of the increase varying by
      state. In 2000, Florida had the highest percentage of persons aged > or =75
      (10.27%) and Alaska the lowest (3.49%). Compared with 1990, older Americans in
      2000 were more likely to be obese (16.3% vs. 13.5%) or diabetic (14.3% vs.
      11.0%). Older Americans in 2000 were also more likely to exercise, consume more
      fruits and vegetables daily, and to have recently obtained a routine medical
      checkup. In addition, they were less likely to smoke tobacco or drink any
      alcohol. CONCLUSIONS: Increases in the population of older people will have a
      tremendous impact on health care in the states and will affect their future plans
      for serving the elderly. Although older Americans are living more healthfully
      than previously, there is an enormous need for targeted health promotion programs
      to prevent chronic diseases in this age group.

PMID- 15158116
TI  - Community and confinement: The evolving experience for isolation for leprosy in
      Carville, Louisiana.

PMID- 15158117
TI  - Olmstead V. L.C. and the Americans with Disabilities Act: implications for public
      health policy and practice.

PMID- 15158118
TI  - The use of knockout mouse technology to achieve tissue selective expression of
      angiotensin converting enzyme.
AB  - The resin angiotensin system (RAS) plays an essential role in blood pressure
      regulation and electrolyte homeostasis. The effecter peptide of the RAS,
      angiotensin II, is produced by angiotensin converting enzyme (ACE) in multiple
      tissues. Genetic deletion of ACE in mice resulted a phenotype of low blood
      pressure, anemia and kidney defects. However, it is not clear whether the lack of
      the systemic or the local production of angiotensin II caused these defects. To
      understand the role of local angiotensin II production, we developed a method to
      achieve tissue specific ACE expression through homologous recombination. In this
      review, we discuss mouse models in which endothelial ACE was eliminated and
      replaced by hepatic ACE. These studies suggest that both circulating angiotensin
      II and local angiotensin II production play a role in angiotensin II generation;
      the elimination of local angiotensin II generation up-regulates systemic
      production and maintains physiologic homeostasis.

PMID- 15158119
TI  - Pyk2/CAKbeta signaling: a novel Ca(2+)-dependent pathway leading to cardiac
      hypertrophy.

PMID- 15158120
TI  - Beta(1)-integrins modulate beta-adrenergic receptor signaling.

PMID- 15158121
TI  - Ca(2+)-sensitive tyrosine kinase Pyk2/CAK beta-dependent signaling is essential
      for G-protein-coupled receptor agonist-induced hypertrophy.
AB  - G-protein-coupled receptor agonists including endothelin-1 (ET-1) and
      phenylephrine (PE) induce hypertrophy in neonatal ventricular cardiomyocytes.
      Others and we previously reported that Rac1 signaling pathway plays an important
      role in this agonist-induced cardiomyocyte hypertrophy. In this study reported
      here, we found that a Ca(2+)-sensitive non-receptor tyrosine kinase, proline-rich
      tyrosine kinase 2 (Pyk2)/cell adhesion kinase beta (CAKbeta), is involved in ET-1
      and PE-induced cardiomyocyte hypertrophy medicated through Rac1 activation. ET
      1, PE or the Ca(2+) inophore, ionomycin, stimulated a rapid increase in tyrosine
      phosphorylation of Pyk2. The tyrosine phosphorylation of Pyk2 was suppressed by
      the Ca(2+) chelator, BAPTA. ET-1- or PE-induced increases in [(3)H]-leucine
      incorporation and expression of atrial natriuretic factor and the enhancement of
      sarcomere organization. Infection of cardiomyocytes with an adenovirus expressing
      a mutant Pyk2 which lacked its kinase domain or its ability to bind to c-Src,
      eliminated ET-1- and PE-induced hypertrophic responses. Inhibition of Pyk2
      activation also suppressed Rac1 activation and reactive oxygen species (ROS)
      production. These findings suggest that the signal transduction pathway leading
      to hypertrophy involves Ca(2+)-induced Pyk2 activation followed by Rac1-dependent
      ROS production.

PMID- 15158122
TI  - Overexpression of the integrin beta(1A) subunit and the beta(1A) cytoplasmic
      domain modifies the beta-adrenergic regulation of the cardiac L-type
      Ca(2+)current.
AB  - Integrins are a family of cell-surface receptors that link the extracellular
      matrix (ECM) to the cellular cytoskeleton. The goal of this study was to
      determine the importance of the integrin beta(1) subunit in regulating cardiac L
      type Ca(2+) channel function. Neonatal rat ventricular myocytes were cultured on
      collagen membranes and infected with adenovirus expressing either the human
      beta(1A) integrin (Adbeta(1A)) or a chimeric protein consisting of the
      cytoplasmic tail domain of the beta(1A) integrin and the
      extracellular/transmembrane domain of the interleukin-2 receptor (AdTAC-beta(1)).
      Expression of the free beta(1) integrin tail (TAC-beta(1)), but not the full
      length beta(1A) integrin, altered cell morphology and disrupted normal cell
      adhesion. When compared with myocytes infected with control virus, neither
      Adbeta(1A) nor AdTAC-beta(1) infection produced any significant change in the
      current vs. voltage relationship of the whole-cell Ca(2+) current (I(Ca)) or the
      kinetics of I(Ca) decay. Expression of TAC-beta(1), but not beta(1A), induced a
      negative shift in the Ca(2+) channel steady-state inactivation curve. Application
      of the beta-adrenergic receptor agonist isoproterenol produced over a 90%
      increase in I(Ca) in control cells, but caused only an 18% increase in myocytes
      overexpressing the full-length beta(1A) integrin. In addition, beta-adrenergic
      stimulation resulted in a 5-10-fold increase in intracellular cAMP levels in
      control cells, but produced no significant response in Adbeta(1A)-infected cells.
      In contrast, expression of TAC-beta(1) was associated with an augmentation in the
      Ca(2+) channel response to isoproterenol (160% increase) and the Ca(2+) channel
      agonist BayK8644. Thus, integrin/ECM interactions may be critical in the
      regulation of I(Ca)

PMID- 15158123
TI  - Transient glucose deprivation causes upregulation of heme oxygenase-1 and
      cyclooxygenase-2 expression in cardiac fibroblasts.
AB  - Transient glucose deprivation (TGD) has been shown to induce a resistance to a
      subsequent ischemia and reperfusion injury in the heart. Induction of
      cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) is known to mediate the
      powerful defensive adaptation of the heart against oxidative stress. In this
      study, we found that a 30-min incubation in the absence of glucose resulted in a
      rapid increased expression of COX-2 and HO-1 in cardiac fibroblasts as examined
      by real-time quantitative polymerase chain reaction (PCR) and western blot
      analysis. Interestingly, TGD increased the generation of reactive oxygen species
      (ROS) and caused the transient phosphorylation of p38 mitogen-activated protein
      kinase (MAPK) as well as the translocation of protein kinase C (PKC)- from the
      cytosolic to the membrane fraction. However, no significant change in the
      distribution of PKC-delta isoform was observed compared with the control.
      Pretreatment of the cells with an antioxidant, N-acetylcysteine (NAC), resulted
      in the inhibition of p38 MAPK phosphorylation and PKC- translocation during TGD.
      In addition, the induction of COX-2 and HO-1 expression by TGD was prevented by
      pretreatment with NAC or SB203580, a p38 MAPK inhibitor. Surprisingly,
      pretreatment with chelerythrine, an inhibitor of PKC, strongly augmented the HO-1
      mRNA expression but blocked the COX-2 mRNA induction by TGD. These results
      demonstrate that briefly removing glucose from cultured cardiac fibroblasts
      induces COX-2 and HO-1 expression via generation of ROS and p38 MAPK
      phosphorylation, while the translocation of PKC- to the membrane fraction may
      participate in the induction of COX-2 but not in the HO-1 expression.

PMID- 15158124
TI  - Effects of follicle stimulating hormone on estradiol-17 beta production and P-450
      aromatase (CYP19) activity and mRNA expression in brown trout vitellogenic
      ovarian follicles in vitro.
AB  - In order to determine whether follicle stimulating hormone (FSH) regulates P-450
      aromatase (P-450 arom) in salmonid fish, we investigated the in vitro effects of
      FSH on estradiol (E(2)) production and P-450 arom activity and expression in
      brown trout (Salmo trutta) vitellogenic ovarian follicles. Brown trout ovarian
      follicles were incubated in the presence of coho salmon FSH and the production of
      E(2) into the medium was measured by RIA, the activity of P-450 arom by the
      tritiated water release assay and the expression of P-450 arom by Northern
      blotting using a homologous cDNA probe obtained by RT-PCR. Results from this
      study indicate that the dose- and time-dependent stimulatory effects of FSH on
      E(2) production are dependent on new RNA and protein synthesis. The basal and FSH
      stimulated E(2) production was completely blocked by fadrozole, a specific
      aromatase inhibitor. FSH was capable of stimulating P-450 arom activity but this
      stimulation was only detectable with short incubation times (30 min) since longer
      incubation times with FSH resulted in the inhibition of P-450 arom activity. In
      addition, FSH increased the steady-state P-450 arom mRNA levels. In conclusion,
      our results indicate, for the first time in teleost fish, that FSH stimulates the
      expression of P-450 arom, as well as its activity, albeit after a short-term
      treatment with FSH, and that FSH plays a fundamental role in the regulation of
      the production of E(2) in the salmonid ovary.

PMID- 15158126
TI  - Low submetamorphic doses of dexamethasone and thyroxine induce complete
      metamorphosis in the axolotl (Ambystoma mexicanum) when injected together.
AB  - Entanglement of functions between the adrenal (or interrenal) and thyroid axis
      has been well described for all vertebrates and can be tracked down up to the
      level of gene expression. Both thyroid hormones and corticosteroids may induce
      morphological changes leading to metamorphosis climax in the neotenic Mexican
      axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis
      was induced with an injection of 25 microg T(4) on three alternate days as judged
      by a decrease in body weight and tail height together with complete gill
      resorption. This injection also resulted in elevated plasma concentrations of
      T(3) and corticosterone. Previous results have indicated that the same dose of
      dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127
      (2002) 157). In a second series of experiments low doses of T(4) (0.5 microg) or
      DEX (5 microg) were ineffective to induce morphological changes. However, when
      these submetamorphic doses were injected together, morphological changes were
      observed within one week leading to complete metamorphosis. It is concluded that
      thyroid hormones combined with corticosteroids are essential for metamorphosis in
      the axolotl and that only high doses of either thyroid hormone or corticosteroid
      can induce morphological changes when injected separately.

PMID- 15158125
TI  - Tilapia islet grafts are highly alloxan-resistant.
AB  - We have previously shown that dose-response studies performed in streptozotocin
      (STZ)-diabetic nude mouse recipients bearing established, functioning islet
      xenografts can be used to directly compare in vivo STZ-sensitivity between donor
      species and that tilapia (fish) islet grafts are exceedingly STZ-resistant. Using
      this method, we tested whether tilapia islets are sensitive to alloxan. Tilapia
      or rat islets were transplanted under the renal capsules of STZ-diabetic nude
      mice. Recipients with normal glucose tolerance tests (GTTs) on day 30-35 were
      injected with increasing i.v. doses of alloxan and blood glucose levels were
      followed for 5-7 days and then GTTs were repeated. Next, mice were killed and
      their grafts/native pancreata examined histologically (including insulin stains).
      Control nude mice were also injected with increasing i.v. doses of alloxan. Based
      upon non-fasting blood glucose levels, GTT, and graft histology, the following
      observations were made: (1) Tilapia islet xenografts were uniformly resistant to
      i.v. doses of 75 mg/kg (n=3), 150 mg/kg (n=4), and 300 mg/kg (n=3). (2) Rat islet
      recipients became uniformly severely diabetic after alloxan i.v. doses of 50-70
      mg/kg (n=6) (i.e., equivalent to the dosage needed to induce diabetes in rats).
      (3) Control nude mice were severely diabetic at doses of 75 mg/kg (4/5) and 150
      mg/kg (n=3/3). Alloxan dose-response studies were also performed in tilapia.
      Interestingly, tilapia appeared more sensitive than tilapia islet grafts.
      Although 75 mg/kg i.v. had little effect in tilapia, higher doses caused severe
      beta cell necrosis, diabetes, and systemic damage; however, this seeming
      discrepancy can be explained as tilapia have about one-quarter of the blood
      volume of mice (i.e., as a percentage of body weight) and so the actual
      concentration in the blood was about 4-fold higher at each dose. We conclude that
      tilapia beta cells are highly resistant to the beta cell toxin alloxan.

PMID- 15158127
TI  - Noninvasive monitoring of adrenocortical activity in carnivores by fecal
      glucocorticoid analyses.
AB  - Measurement of glucocorticoid metabolites in feces has become an accepted method
      for the noninvasive evaluation of adrenocortical activity. The objective of this
      study was to determine if a simple cortisol enzyme immunoassay (EIA) was suitable
      for monitoring adrenocortical activity in a variety of carnivore species.
      Performance of the cortisol EIA was gauged by comparison to a corticosterone
      radioimmunoassay (RIA) that has been used for measuring glucocorticoid
      metabolites in feces of numerous species. Tests for parallelism and extraction
      efficiency were used to compare the cortisol EIA and corticosterone RIA across
      eight species of carnivores (Himalayan black bear, sloth bear, domestic cat,
      cheetah, clouded leopard, black-footed ferret, slender-tailed meerkat, and red
      wolf). The biological relevance of immunoreactive glucocorticoid metabolites in
      feces was established for at least one species of each Carnivora family studied
      with an adrenocorticotropic hormone (ACTH) challenge. High performance liquid
      chromatography (HPLC) analysis of fecal extracts for each species revealed (1)
      the presence of multiple immunoreactive glucocorticoid metabolites in feces, but
      (2) the two immunoassays measured different metabolites, and (3) there were
      differences across species in the number and polarities of metabolites identified
      between assay systems. ACTH challenge studies revealed increases in fecal
      metabolite concentrations measured by the cortisol EIA and corticosterone RIA of
      approximately 228-1145% and approximately 231-4150% above pre-treatment baseline,
      respectively, within 1-2 days of injection. Concentrations of fecal
      glucocorticoid metabolites measured by the cortisol EIA and corticosterone RIA
      during longitudinal evaluation (i.e., >50 days) of several species were
      significantly correlated (P<0.0025, correlation coefficient range 0.383-0.975).
      Adrenocortical responses to physical and psychological stressors during
      longitudinal evaluations varied with the type of stimulus, between episodes of
      the same stimulus, and among species. Significant elevations of glucocorticoid
      metabolites were observed following some potentially stressful situations
      [anesthesia (2 of 3 subjects), restraint and saline injection (2 of 2 subjects),
      restraint and blood sampling (2 of 6 episodes), medical treatment (1 of 1
      subject)], but not in all cases [e.g., gonadotropin injection (n=4), physical
      restraint only (n=1), mate introduction/breeding (n=1), social tension (n=1),
      construction (n=2) or relocation (n=1)]. Results reinforced the importance of an
      adequate baseline period of fecal sampling and frequent collections to assess
      adrenocortical status. The corticosterone RIA detected greater adrenocortical
      responses to exogenous ACTH and stressful exogenous stimuli in the Himalayan
      black bear, domestic cat (female), cheetah, clouded leopard, slender-tailed
      meerkat, and red wolf, whereas the cortisol EIA proved superior to resolving
      adrenocortical responses in the black-footed ferret and domestic cat (male).
      Overall results suggest the cortisol EIA tested in this study offers a practical
      method for laboratories restricted in the usage of radioisotopes (e.g.,
      zoological institutions and field facilities) to integrate noninvasive monitoring
      of adrenocortical activity into studies of carnivore behavior and physiology.

PMID- 15158129
TI  - Changes in expression of AVT and AVT receptor (VT1) gene in hypothalamus and
      shell gland in relation to egg laying in white leghorn hen.
AB  - Oviposition is a complex phenomenon involving various regulatory mechanisms at
      the neuroendocrine levels. Present study was designed to access the changes in
      arginine vasotocin (AVT) and its receptor (VT1) gene expression in relation to
      the time of egg laying of white leghorn hen. The expression of AVT gene (Northern
      blot analysis and in situ hybridization) in the hypothalamus and localization of
      ir-AVT in the magnocellular neurons of paraventricular nuclei was studied 2 h
      before (-2 h), immediately after (0 h) and 2 h after (+2 h) egg laying.
      Simultaneous changes in the AVT and VT1 receptor gene in the shell gland, which
      finally responds to AVT for smooth muscle contraction and expulsion of egg, were
      also determined by semi-quantitative reverse transcriptase-polymerase chain
      reaction. The findings indicated increased hypothalamic AVT gene expression
      immediately after egg laying (0 h) when compared to 2 h before and 2 h after egg
      laying. AVT receptor gene expression in the shell gland also followed the same
      pattern. However, AVT gene expression in the shell gland, unlike that of
      hypothalamus was higher at -2 h compared to 0 and +2 h of oviposition. While
      highly significant increase was noted in plasma AVT concentration at the time of
      egg laying, other parameters such as plasma osmolality and ionic concentration
      (Na(+), K(+), Ca(2+), and Cl(-)) did not show any change. It is suggested that in
      addition to increased hypothalamic AVT transcript and peripheral release, local
      synthesis of AVT in the shell gland (paracrine release) may contribute to the
      contraction of shell gland smooth muscles during egg laying. Moreover, these
      findings clearly indicate temporal correlation of AVT and its receptor gene
      expression in different tissues during oviposition.

PMID- 15158128
TI  - Expression of natriuretic peptides, nitric oxide synthase, and guanylate cyclase
      activity in frog mesonephros during the annual cycle.
AB  - Natriuretic peptides (NPs), a family of structurally related hormones and nitric
      oxide (NO), generated by nitric oxide synthase (NOS), are believed to be involved
      in the regulation of fluid balance and sodium homeostasis. Differential
      expression and regulation of these factors depend on both physiological and
      pathological conditions. Both NPs and NO act in target organs through the
      activation of guanylate cyclase (GC) and the generation of guanosine 3',5'-cyclic
      monophosphate (cGMP), which is considered a common messenger for the action of
      these factors. The present study was designed to investigate--by histochemical
      methods--the expression of some NPs (proANP and ANP) and isoforms of NOS
      (neuronal NOS, nNOS, and inducible NOS, iNOS) in the mesonephros of Rana
      esculenta in different periods of the year including hibernation, to evaluate
      possible seasonal changes in their expression. We also studied the enzyme
      activity of NOS-related nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPHd) and of GC. The experiments were performed on pieces of kidney of R.
      esculenta collected in their natural environment during active and hibernating
      life. The study was carried out using immunohistochemical techniques to
      demonstrate proANP, ANP, and some NOS isoforms. Antigen capture by enzyme linked
      immunosorbent assay (ELISA) was also performed to determine the presence of NPs
      in the frog kidney extract. Enzyme histochemistry was used to demonstrate the NOS
      related NADPHd activity at light microscopy; GC activity was visualized at the
      electron microscope, using cerium as capture agent. The application of the
      immunohistochemical techniques demonstrated that frog mesonephros tubules express
      different patterns of distribution and/or expression of ANP and NOS during the
      annual cycle. Comparing the results obtained on active and hibernating frogs has
      provided interesting data; the NOS/NADPHd and GC activities showed some
      variations as well. Furthermore, the presence of NPs in the frog kidney extract
      was evidenced by dose-dependent response in the ELISA. The data suggest that both
      ANP and NO are intra-renal paracrine and/or autocrine factors which may modulate
      the adaptations of frog renal functions to seasonal changes through the action of
      the cGMP generated from GC activity.

PMID- 15158130
TI  - Receptors for vasoactive intestinal peptide and pituitary adenylate cyclase
      activating polypeptide in turkey cerebral cortex: characterization by [125I]-VIP
      binding and effects on cyclic AMP synthesis.
AB  - Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) in turkey cerebral cortex were characterized using
      two approaches: (1) in vitro radioreceptor binding of [125I]-VIP, and (2) effects
      of peptides from the PACAP/VIP/secretin family on cyclic AMP formation. The
      binding of [125I]-VIP to turkey cortical membranes was rapid, stable, and
      reversible. Saturation analysis resulted in a linear Scatchard plot, suggesting
      binding to a single class of high affinity receptor binding sites with a Kd of
      0.70 nM and a Bmax of 52 fmol/mg protein. Various peptides displaced the specific
      binding of 0.12 nM [125I]-VIP to turkey cerebral cortical membranes in a
      concentration-dependent manner. The relative rank order of potency of the tested
      peptides to inhibit [125I]-VIP binding to turkey cerebrum was: PACAP38
      approximately PACAP27 approximately chicken VIP approximately mammalian VIP >>>
      PHI >> secretin, chicken VIP16-28 (inactive). About 65% of specific [125I]-VIP
      binding sites in turkey cerebral cortex was sensitive to Gpp(NH)p, a
      nonhydrolysable analogue of GTP. PACAP38, PACAP27, chicken VIP and, to a lesser
      extent, mammalian VIP potently stimulated cyclic AMP formation in turkey cerebral
      cortical slices in a concentration-dependent manner, displaying EC50 values of
      8.7 nM (PACAP38), 21.3 nM (PACAP27), 67.4 nM (chicken VIP), and 202 nM (mammalian
      VIP). On the other hand, PHI and secretin very weakly affected the nucleotide
      production. The obtained results indicate that cerebral cortex of turkey contains
      VPAC type receptors that are positively linked to cyclic AMP-generating system
      and are labeled with [125I]-VIP.

PMID- 15158131
TI  - Establishment of a real-time RT-PCR for the determination of absolute amounts of
      IGF-I and IGF-II gene expression in liver and extrahepatic sites of the tilapia.
AB  - We developed a one-tube two-temperature real-time RT-PCR that allows to
      absolutely quantify the gene expression of hormones using the standard curve
      method. As our research focuses on the expression of the insulin-like growth
      factors (IGFs) in bony fish, we established the technique for IGF-I and IGF-II
      using the tilapia (Oreochromis niloticus) as model species. As approach, we used
      primer extension adding a T7 phage polymerase promoter (21 nt) to the 5' end of
      the antisense primers. This procedure avoids the disadvantages arising from
      plasmids. Total RNA extracted from liver was subjected to conventional RT-PCR to
      create templates for in vitro transcription of IGF-I and IGF-II cRNA. Correct
      template sizes including the T7 promoter were verified (IGF-I: 91 nt; IGF-II: 94
      nt). The PCR products were used to create IGF-I and IGF-II cRNAs which were
      quantified in dot blot by comparison with defined amounts of standardised
      kanamycin mRNA. Standardised threshold cycle (Ct) values for IGF-I and IGF-II
      mRNA were achieved by real-time RT-PCR and used to create standard curves. To
      allow sample normalisation the standard curve was also established for beta-actin
      as internal calibrator (template: 86 nt), and validation experiments were
      performed demonstrating similar amplification efficiencies for target and
      reference genes. Based on the standard curves, the absolute amounts of IGF-I and
      IGF-II mRNA were determined for liver (IGF-I: 8.90+/-1.90 pg/microg total RNA,
      IGF-II: 3.59+/-0.98 pg/microg total RNA) and extrahepatic sites, such as heart,
      kidney, intestine, spleen, gills, gonad, and brain considering the different
      lengths of cRNAs and mRNAs by correction factors. The reliability of the method
      was confirmed in additional experiments. The amplification of descending
      dilutions of cRNA and total liver RNA resulted in parallel slopes of the
      amplification curves. Furthermore, amplification plots of the standard cRNA and
      the IGF-I and IGF-II mRNAs showed signals starting at the expected Ct values.
      Thus, the one-tube RT-PCR described here is highly sensitive (detection level
      approximately 2 pg/microg total RNA) and allows precise absolute quantification.
      The method is rapid as there are neither separate reverse transcriptions nor post
      amplification steps, and can be executed with low risk of contamination.
      Therefore, it will be helpful when investigating gene expression in any species
      and tissue whenever absolute levels are of concern.

PMID- 15158132
TI  - Cloning and characterization of teneurin C-terminus associated peptide (TCAP)-3
      from the hypothalamus of an adult rainbow trout (Oncorhynchus mykiss).
AB  - Neuropeptides that evolved early in metazoan evolution may possess much larger
      networks of paralogous genes than later evolving peptides due to the increased
      exposure to gene and genomic duplication events. The corticotropin-releasing
      factor family of peptides, which also include invertebrate CRF-like peptides, are
      a candidate group that appear to have an early origin. We have attempted to find
      additional paralogous genes to the CRF family by doing a low-stringency screen of
      a rainbow trout hypothalamic cDNA library using a hamster urocortin probe. A
      clone was identified that represented the rainbow trout ortholog of teneurin-3.
      The C-terminal region of the last exon teneurin transmembrane protein gene
      possesses a neuropeptide-like sequence with a primary structure similarity to the
      corticotropin-releasing factor family of peptides. We have called this sequence
      teneurin C-terminal associated peptide (TCAP). The predicted peptide is 40
      residues long and possesses an expected pyroglutamyl residue in the first
      position and an amidated carboxy terminus. A synthetic version of the rainbow
      trout (rt) TCAP-3 is potent at increasing the concentration of cAMP and
      stimulating proliferation in a neuronal cell line. The synthetic peptide can also
      either increase or decrease the expression of the teneurin-1 gene, depending upon
      its concentration. The teneurin/TCAP system may represent a novel and highly
      conserved regulatory signalling system in the vertebrate brain.

PMID- 15158133
TI  - Calcium cycling in heart failure: how the fast became too furious.

PMID- 15158134
TI  - Ghrelin in the heart and growth hormone: which is chicken, which is egg?

PMID- 15158136
TI  - Adenosine receptors, heart rate, and cardioprotection.

PMID- 15158135
TI  - Unveiling the transcriptional control of the developing cardiac conduction
      system.

PMID- 15158137
TI  - Altered cAMP-mediated signalling and its role in the pathogenesis of dilated
      cardiomyopathy.
AB  - Alterations in the level and function of proteins involved in cAMP-mediated
      signalling are important in the pathophysiology and treatment of dilated
      cardiomyopathy. What is unclear is the extent to which these alterations, which
      attenuate receptor-stimulated cAMP generation, contribute to the pathogenesis of
      dilated cardiomyopathy and the extent to which they constitute a beneficial
      compensatory response. Studies in animals involving overexpression and ablation
      of proteins or peptides involved in cAMP-mediated signalling have yielded
      disparate results that are difficult to reconcile with a simple hypothesis. Our
      ability to understand these differences is limited by the lack of information on
      how these different genetic manipulations affect the phosphorylation of
      individual substrates of protein kinase A (PK-A) through which cAMP signals are
      transduced. This is important in view of evidence that the phosphorylation of
      individual PK-A substrates can be regulated selectively in different
      intracellular compartments, and that the phosphorylation of some PK-A substrates
      is increased in dilated cardiomyopathy while the phosphorylation of others is
      reduced. Approaches that quantify changes in the phosphorylation of individual PK
      A substrates in models of dilated cardiomyopathy will provide information that
      may allow a better understanding of the pathogenesis of the syndrome and a more
      rational approach to its treatment.

PMID- 15158138
TI  - Cardiovascular and renal function of angiotensin II type-2 receptors.
AB  - While all of the well-known cardiovascular and renal effects of angiotensin II
      (ANG) are attributed to the ANG type-1 (AT(1)) receptor, much less is known about
      the function of ANG type-2 (AT(2)) receptors. This review focuses on progress
      made in AT(2) receptor research over the past 10 years mainly enabled by the
      availability of AT(2) receptor-deficient mice. Two general mechanisms regarding
      AT(2) receptor-mediated actions emerge from recent experiments. Firstly, AT(2)
      receptor stimulation inhibits growth and promotes apoptosis, an important
      mechanism during development and tissue remodeling. Secondly, ANG stimulates the
      release of nitric oxide (NO)/cGMP via AT(2) receptor activation, as described in
      the aorta, heart, and kidney. This effect appears to be indirectly mediated by
      the modulation of bradykinin release. Thus, activation of AT(2) receptors may be
      potentially protective and appears to oppose the effects mediated by AT(1)
      receptors. The question whether AT(2) receptors are activated in patients with
      elevated ANG levels when treated with AT(1) receptor antagonists and whether
      these effects are relevant awaits further clarification.

PMID- 15158139
TI  - Phospholamban gene ablation improves calcium transients but not cardiac function
      in a heart failure model.
AB  - Decreased amplitude and slower kinetics of cardiomyocyte intracellular calcium
      (Ca(i)(2+)) transients may underlie the diminished cardiac function observed in
      heart failure. These alterations occur in humans and animals with heart failure,
      including the TNF1.6 mouse model, in which heart failure arises from cardiac
      specific overexpression of tumor necrosis factor alpha (TNF alpha). OBJECTIVE:
      Since ablation of phospholamban expression (PLBKO) removes inhibition of the
      sarcoplasmic reticulum (SR) Ca(2+) pump, enhances SR Ca(2+) uptake and increases
      contractility, we assessed whether ablation of phospholamban expression could
      improve cardiac function, limit remodeling, and improve survival in the TNF1.6
      model of heart failure. METHODS: We bred PLBKO with TNF1.6 mice and characterized
      the progeny for survival, cardiac function (echocardiography), cardiac remodeling
      (hypertrophy, dilation, fibrosis), and Ca(2+)(i) transients and contractile
      function of isolated cardiomyocytes. RESULTS: PLB ablation did not improve
      survival, cardiac function, or limit cardiac chamber dilation and hypertrophy in
      TNF1.6 mice (TKO mice). However, contractile function and Ca(2+)(i) transients
      (amplitude and kinetics) of isolated TKO cardiomyocytes were markedly enhanced.
      This discordance between unimproved cardiac function, and enhanced Ca(2+)(i)
      cycling and cardiomyocyte contractile parameters may arise from a continued
      overexpression of collagen and decreased expression of gap junction proteins
      (connexin 43) in response to chronic TNF alpha stimulation. CONCLUSIONS:
      Enhancement of intrinsic cardiomyocyte Ca(2+)(i) cycling and contractile function
      may not be sufficient to overcome several parallel pathophysiologic processes
      present in the failing heart.

PMID- 15158140
TI  - Growth hormone releasing peptide (ghrelin) is synthesized and secreted by
      cardiomyocytes.
AB  - OBJECTIVE: Ghrelin, the endogenous ligand of growth hormone secretagogue receptor
      (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of
      growth hormone (GH) and promotes appetite and adiposity. It has also been
      reported to increase myocardial contractility, induce vasodilation, and protect
      against myocardial-infarction-induced heart failure. Though principally gastric
      in origin, it is also produced by other tissues. This work investigated whether
      cardiomyocytes synthesize and secrete ghrelin, and how its production in these
      cells responds to stress and exogenous apoptotic agents. METHODS: Ghrelin and its
      receptor expression was studied by RT-PCR, immunohistochemistry, and competitive
      binding studies in mouse adult cardiomyocyte cell line HL-1, and primary cultured
      human cardiomyocytes. Ghrelin accumulation in cardiomyocyte culture medium was
      measured by radioimmunoassay. Viability and apoptosis assays were carried on by
      MTT and Hoechst dye vital staining, respectively. RESULTS: RT-PCR showed that HL
      1 cells produce mRNAs for both ghrelin and GHS-R, and that GHS-R1a is expressed
      in human cardiomyocytes; and competitive binding studies using (125)I-labelled
      ghrelin showed efficient constitutive expression of GHS-R at the surface of HL-1
      cells. Immunohistochemistry confirmed the presence of ghrelin in the cytoplasm of
      HL-1 cells and of isolated human cardiomyocytes in primary culture.
      Radioimmunoassay showed that ghrelin was secreted by HL-1 cells and human
      cardiomyocytes into the culture medium. Ghrelin did not modify the viability of
      HL-1 cells subjected to 12-h starvation, but did protect against the apoptosis
      inducer cytosine arabinoside (AraC). Finally, production of ghrelin mRNA in HL-1
      cardiomyocytes was reduced by AraC but increased if exposure to AraC was preceded
      by GH treatment. CONCLUSIONS: Ghrelin is synthesized and secreted by isolated
      murine and human cardiomyocytes, probably with paracrine/autocrine effects, and
      may be involved in protecting these cells from apoptosis.

PMID- 15158141
TI  - The transcriptional repressor Tbx3 delineates the developing central conduction
      system of the heart.
AB  - OBJECTIVE: The molecular mechanisms that regulate the formation of the conduction
      system are poorly understood. We studied the developmental expression pattern and
      functional aspects of the T-box transcription factor Tbx3, a novel marker for the
      murine central conduction system (CCS). METHODS: The patterns of expression of
      Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular
      chamber-type myocardium in the developing heart, were analyzed in mice by in situ
      hybridization and three-dimensional reconstruction analysis. The function of Tbx3
      in regulating Nppa and Cx40 promoter activity was studied in vitro. RESULTS: In
      the formed heart, Tbx3 is expressed in the sinoatrial node (SAN),
      atrioventricular node (AVN), bundle and proximal bundle branches (BBs), as well
      as the internodal regions and the atrioventricular region. Throughout cardiac
      development, Tbx3 is expressed in an uninterrupted myocardial domain that extends
      from the sinoatrial node to the atrioventricular region. This expression domain
      is present in the looping heart tube from E8.5 onwards. Expression of the chamber
      type myocardial markers is specifically absent from the Tbx3 expression domain.
      Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the
      synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5. CONCLUSION: We
      identified the T-box transcription factor Tbx3 as a novel and accurate marker for
      the central conduction system. Our analysis implicates a role for Tbx3 in
      repressing a chamber-specific program of gene expression in regions from which
      the components of the central conduction system are subsequently formed.

PMID- 15158142
TI  - Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in
      mice overexpressing A(3) adenosine receptors.
AB  - OBJECTIVE: An increased expression of adenosine receptors is a promising target
      for gene therapy aimed at protecting the myocardium against ischemic damage, but
      may alter cardiac electrophysiology. We therefore studied the effects of heart
      directed overexpression of A(3) adenosine receptors (A(3)ARs) at different gene
      doses on sinus and atrio-ventricular (AV) nodal function in mice. METHODS AND
      RESULTS: Mice with heart-specific overexpression of A(3)AR at high (A(3)(high))
      or low (A(3)(low)) levels and their wild-type littermates were studied.
      Telemetric electrocardiogram (ECG) recordings in adult freely moving A(3)(high)
      mice showed profound sinus bradycardia resulting in either ventricular escape
      rhythms or an incessant bradycardia-tachycardia syndrome (minimal heart rate
      A(3)(high) 217+/-25*; WT 406+/-21 beats/min, all values as mean+/-S.E.M., n=7 per
      genotype, *p<0.05). Exercise attenuated bradycardia in A(3)(high) mice (maximal
      heart rate A(3)(high) 650+/-13*; WT 796+/-13 beats/min) and first-degree AV nodal
      block was present (PQ interval A(3)(high) 36+/-4*; WT 23+/-5 ms). Isolated hearts
      showed complete heart block (10/17 A(3)(high)* vs. 1/17 WT). Atrial bradycardia
      and AV block were already present 3 weeks after birth. Doppler echocardiography
      revealed atrial dysfunction and progressive atrial enlargement that was moderate
      at 3 and 8 weeks, and progressed at 12 and 21 weeks of age (all p<0.05 vs. WT).
      Atrial contractility and sarcoendoplasmic Ca(2+) ATPase (SERCA) 2a protein
      expression were reduced in isolated left A(3)(high) atria at the age of 14 weeks.
      Fibrosis was present in left A(3)(high) atria at 14 weeks, but not at 5 weeks of
      age. A(3)(low) mice had first-degree AV block without arrhythmias or structural
      changes. CONCLUSIONS: Heart-directed overexpression of A(3)AR resulted in gene
      dose-dependent AV block and pronounced sinus nodal dysfunction in vivo. Profound
      bradycardia heralded atrial and ventricular dilatation, dysfunction, and
      fibrosis. In contrast to A(1) adenosine receptors (A(1)AR), the effects of A(3)AR
      overexpression were attenuated during exercise. This may have implications for
      the physiology of sinus nodal regulation and for therapeutic attempts to increase
      the expression of adenosine receptors.

PMID- 15158144
TI  - Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte
      model for atrial fibrillation.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a progressive disease. Previously,
      clinical and animal experimental studies in AF revealed a variety of myocyte
      remodeling processes including L-type Ca(2+) channel reduction and structural
      changes, which finally result in electrical remodeling and contractile
      dysfunction. There are indications that myocyte remodeling is mediated by Ca(2+)
      overload induced calpain activation. To study in more detail the mechanisms
      underlying myocyte remodeling and to develop strategies for drug-interference, we
      utilised a paced cell model for AF. METHODS AND RESULTS: HL-1 atrial myocytes
      were subjected to a 10 times increase in rate over basal values by electrical
      field stimulation at 5 Hz. It was found that 24-h pacing reduced plasmalemmal
      levels of L-type Ca(2+) channel alpha 1C subunit by -72% compared to controls. No
      changes in amount of the potassium channel subunits Kv4.3 and Kv1.5 were found.
      Pacing also induced marked structural changes; myolysis and nuclear condensation,
      paralleled by a 14-fold increase in calpain activity. The pacing-induced
      reduction of L-type Ca(2+) channel protein was fully prevented by treatment with
      verapamil, the active stereoisomer of methoxyverapamil D600, the calpain
      inhibitors PD150606 and E64d, and LaCl(3). Interestingly, PD150606, E64d and
      LaCl(3), but not (methoxy)verapamil, prevented structural changes. CONCLUSIONS:
      Paced HL-1 atrial myocytes undergo myocyte remodeling similar to that found in
      myocytes from patients with AF. Calcium influx independent of the L-type Ca(2+)
      channel and subsequent activation of calpain represent key features in the
      progression towards overt structural changes. Calpain inhibition may therefore
      represent a useful lead for therapeutic intervention in AF.

PMID- 15158143
TI  - The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte
      contractility via a direct inhibition of Ik,slow currents.
AB  - OBJECTIVE: Phosphoinositide 3-kinase (PI3K) is a key component in regulating
      myocardial growth, survival and contractility. LY294002 and wortmannin are two
      PI3K inhibitors used widely to establish the role of PI3K. The goal of this study
      was to examine the effects of acute application of LY294002 and wortmannin on
      cardiac myocyte contractility and underlying mechanisms. METHODS: Patch-clamp,
      indo-1 epifluorescence and video-edge detection techniques were used to measure
      outward K(+) currents, action potentials (AP), Ca(2+) transients and shortening
      of myocytes isolated from mouse left ventricular free wall. RESULTS: In field
      stimulated myocytes, LY294002 (10 micromol/l) increased Ca(2+) transient
      amplitude by 23%, and cell shortening amplitude by 60% in the absence or presence
      of wortmannin, while wortmannin alone had no effect. LY294002 (but not
      wortmannin) prolonged AP duration by specifically inhibiting slowly inactivating
      K(+) currents (i.e., the 4-aminopyrydine-sensitive I(k,slow1) and the
      tetraethylammonium-sensitive I(k,slow2)), leading to an increase in sarcoplasmic
      reticular Ca(2+) levels. It appeared that the AP prolongation was responsible for
      elevated contractility since AP-clamp of myocytes with prolonged APs (recorded in
      LY294002-treated myocytes) induced a 29% increase in cell shortening compared
      with control APs, while LY294002 application did not increase contractility in
      voltage-clamp studies using either step or AP depolarizations. CONCLUSIONS: The
      putative PI3K inhibitor LY294002 increases Ca(2+) release and myocyte
      contractility via direct inhibition of cardiac I(k,slow) and AP prolongation,
      thus limiting the usefulness of this agent in the analyses of the role of PI3K in
      heart function.

PMID- 15158145
TI  - Functional consequences of detubulation of isolated rat ventricular myocytes.
AB  - OBJECTIVE: Recent work has suggested that Na(+)/Ca(2+) exchange (NCX) and L-type
      Ca(2+) current (I(Ca)) are located predominantly in the t-tubules of cardiac
      ventricular myocytes, which therefore represent a microdomain for the regulation
      of intracellular Na(+) (Na(i)) and Ca(2+) (Ca(i)). The aim of this study was to
      investigate the role of the t-tubules in the response of Ca(i) and contraction to
      interventions that alter the transsarcolemmal Na(+)gradient. METHODS:
      Enzymatically isolated and detubulated Wistar rat ventricular myocytes were
      investigated using fluorescence microscopy and optical detection of cell length.
      RESULTS: In unstimulated cells, spontaneous contractile activity increased when
      extracellular [Na(+)] was decreased or strophanthidin (100 microM) was added to
      the bathing solution, but the increase was significantly smaller in detubulated
      cells than in control cells. In electrically stimulated cells, strophanthidin
      increased Na(i) to a similar extent in normal and detubulated cells, although the
      associated increase in Ca(2+) transient amplitude and contraction were
      significantly smaller in detubulated cells. Similarly, tetrodotoxin (TTX, 10
      microM) attenuated the Ca(2+) transient and contraction less in detubulated than
      in control cells. Increasing stimulation rate (0.05-1 Hz) caused little change or
      a small increase in contraction amplitude in control cells, but a significant
      decrease in contraction amplitude in detubulated cells, although the change of
      Na(i) caused by increasing stimulation rate from 0 to 1 Hz was not significantly
      different in the two cells types. CONCLUSION: It is concluded that although some
      Na/K ATPase, NCX and Na(+)channel activity is present on the surface membrane,
      the t-tubules play a major role in the modulation of contraction via NCX,
      allowing changes of the transsarcolemmal Na(+)gradient to be translated into
      changes of Ca(i).

PMID- 15158146
TI  - Enhanced sarcolemmal Ca2+ efflux reduces sarcoplasmic reticulum Ca2+ content and
      systolic Ca2+ in cardiac hypertrophy.
AB  - OBJECTIVE: Recent work has identified reductions in the systolic Ca(2+) transient
      in cardiac disease states. The aim of the present study was to identify the
      mechanisms responsible for perturbations of intracellular calcium homeostasis in
      isolated cardiac myocytes and determine if such changes can quantitatively
      explain the reduced systolic Ca(2+) transient. METHODS: Left ventricular
      hypertrophy (LVH) was induced by aortic coarctation in adult ferrets. Changes in
      intracellular Ca(2+) regulation, sarcolemmal Ca(2+) fluxes and SR function were
      measured in single left ventricular cardiac myocytes. RESULTS: Cardiac
      hypertrophy was associated with a 29% increase in action potential duration
      (APD(90)); a 48% reduction in the amplitude of and 19% slowing in the rate of
      decay of the systolic Ca(2+) transient; a 20% decrease in SR Ca(2+) content and a
      36% increase in inward Na(+)-Ca(2+) exchange current for a given change in
      [Ca(2+)](i) (all P<0.05). Peak L-type Ca(2+) current density, integrated Ca(2+)
      influx and SERCA2a protein levels remained unchanged in hypertrophy. By
      determining the relationship between SR Ca(2+) content and systolic Ca(2+), the
      reduction in SR Ca(2+) content quantitatively explained the smaller systolic
      Ca(2+) transient. The reduced SR Ca(2+) content also accounted for a smaller
      fractional release of Ca(2+) from the SR and lower gain of excitation contraction
      coupling in cardiac hypertrophy. The increased sarcolemmal-mediated Ca(2+) efflux
      was sufficient to explain the reduction in SR Ca(2+) content. CONCLUSIONS: The
      findings indicate that the primary mechanism underlying the smaller systolic
      Ca(2+) transient amplitude in cardiac hypertrophy is decreased SR Ca(2+) content
      occurring as a consequence of reduced SR Ca(2+)-ATPase-mediated Ca(2+) uptake and
      increased sarcolemmal-mediated Ca(2+) efflux from the cell. The increased Na(+)
      Ca(2+) exchange-mediated current for a given change in intracellular Ca(2+)
      concentration provides a mechanism for the development of arrhythmias in the face
      of a reduced SR Ca(2+) load in cardiac hypertrophy.

PMID- 15158147
TI  - Transcriptional regulation of FGF-2 gene expression in cardiac myocytes.
AB  - OBJECTIVE: Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect
      through cell surface receptor signaling and may play a role in the normal
      maintenance of a healthy myocardium. One mechanism of FGF-2 release from
      contracting cardiomyocytes is through transient sarcolemmal disruption, with
      accumulation in the extracellular matrix. Continuous FGF-2 release would require
      a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity
      in cardiomyocytes as a potential target for optimizing cardioprotection. METHODS
      AND RESULTS: To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM),
      were transfected with approximately 1 or 0.1 kb of rat FGF-2 promoter sequences
      linked to luciferase, -1058FGF-2p.luc and -110FGF-2p.luc, and treated with or
      without FGF-2. FGF-2 promoter activity was significantly increased approximately
      2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains
      putative binding sites for the early growth response-1 (Egr-1) and stimulating
      protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased 
      1058FGF-2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1
      and overlapping Sp1 sites did not blunt the response of -110FGF-2p.luc to FGF-2
      treatment but did significantly reduce basal promoter activity. Transgenic mice
      expressing -1058FGF-2p.luc were treated with isoproterenol (IsP) to increase
      heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated
      significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels
      were also detected. In contrast, no effect of IsP was seen on -1058FGF-2p.luc or 
      110FGF-2p.luc in transfected NRCMs. CONCLUSIONS: FGF-2 released from
      cardiomyocytes may act to regulate its own synthesis at the transcriptional
      level. The mechanism does not appear to require an intact Egr-1 site in the
      proximal promoter region. This may, however, reflect redundancy in the control of
      FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.

PMID- 15158148
TI  - Norepinephrine induces apoptosis in neonatal rat cardiomyocytes through a
      reactive oxygen species-TNF alpha-caspase signaling pathway.
AB  - OBJECTIVE: Norepinephrine (NE)-induced apoptosis in cardiomyocytes is an
      important cause of heart failure. Previous studies revealed that reactive oxygen
      species (ROS) are involved in apoptosis. Tumor necrosis factor-alpha (TNF), a
      well-known mediator that stimulates apoptosis, is not only produced by
      macrophages but also by cardiomyocytes. Until now, the role of TNF and its
      relationship to ROS in NE-induced apoptosis of cardiomyocytes have never been
      investigated. METHODS: Neonatal rat cardiomyocytes were treated with various
      concentrations of NE. Apoptosis of cardiomyocytes was determined using the TUNEL
      assay. The level of secreted TNF was measured by ELISA and TNF mRNA expression
      was determined by semiquantitative reverse transcriptional polymerase chain
      reaction. Caspase activity was measured by a fluorogenic protease assay kit. Anti
      TNF antibodies, caspase inhibitors and antioxidants (N-acetyl-L-cysteine or
      vitamin C) were added to determine if they could inhibit the apoptotic effect of
      NE. RESULTS: NE induced apoptosis of cardiomyocytes in a dose- and time-dependent
      manner. NE up-regulated TNF mRNA expression and increased TNF secretion and
      caspase-2,-3,-6, and -9 activities. A neutralizing anti-TNF antibody and caspase
      2 and -3 inhibitors significantly attenuated NE-induced apoptosis. Antioxidants
      completely abrogated NE-induced TNF secretion, caspase activation, and apoptotic
      death. CONCLUSION: NE induced apoptosis in neonatal rat cardiomyocytes through a
      ROS-TNF-caspase signaling pathway.

PMID- 15158150
TI  - Tumor necrosis factor alpha as an endogenous stimulator for circulating coupling
      factor 6.
AB  - OBJECTIVE: We recently showed that mitochondrial coupling factor 6 (CF6) is
      present as a pressor substance and a prostacyclin inhibitor in systemic
      circulation. However, the regulation mechanism for circulating CF6 is unknown. We
      investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the
      generation and release of CF6. METHODS AND RESULTS: We used two kinds of cells,
      human umbilical vein endothelial cells (HUVEC) and ECV-304. The concentration of
      CF6 in the medium increased with time in both ECV-304 and HUVEC. Treatment of ECV
      304 and HUVEC with TNF-alpha enhanced the release of CF6 in a dose-dependent
      manner concomitantly with the decrease in CF6 content in the mitochondria at 24
      h. The released CF6 was characterized to be an active full-length peptide by
      Western blot. The ratio of CF6 to GAPDH mRNA, measured by real-time polymerase
      chain reaction, was 1.7 fold increased at 1 h after exposure to TNF-alpha in ECV
      304 and HUVEC. This enhanced gene expression and release was blocked or
      suppressed by 70% by stable transfection of dominant negative mutant I kappa B
      kinase alpha whose efficacy was confirmed by blockade of translocation of NF
      kappa B p65 protein and of degradation of I kappa B alpha protein. Flow cytometry
      analysis revealed that the cell surface-associated CF6 was significantly
      increased at 24 h after TNF-alpha in a dose-dependent manner. CONCLUSIONS: TNF
      alpha stimulates the gene expression of CF6 via activation of NF-kappa B
      signaling pathway, and promotes the release of CF6 from ECV-304 and HUVEC.

PMID- 15158149
TI  - Critical timing of L-arginine treatment in post-ischemic myocardial apoptosis
      role of NOS isoforms.
AB  - BACKGROUND: The role of nitric oxide (NO) in apoptotic cell death has been
      extensively studied in recent years. However, reported results are inconsistent
      and often controversial, and the mechanisms underlying its diverse effects in
      apoptosis regulation remain unidentified. The present study attempted to
      determine whether in vivo administration of L-arginine, the substrate for NOS, at
      different time points during the course of myocardial ischemia and reperfusion
      may differentially regulate post-ischemic myocardial apoptosis, and if so, to
      investigate the mechanisms involved. METHODS AND RESULTS: Male adult rats were
      subjected to 30 min of myocardial ischemia followed by 5 h of reperfusion. L
      Arginine was administered as a bolus at either 10 min before (early treatment) or
      3 h after reperfusion (late treatment). There was no difference in myocardial
      eNOS expression between any groups studied. Myocardial iNOS expression was
      detected at 3 h after reperfusion but not at 1 h after reperfusion.
      Administration of L-arginine 10 min before reperfusion markedly decreased TUNEL
      positive staining cardiomyocytes, reduced myocardial caspase-3 activity,
      inhibited iNOS expression, and reduced myocardial nitrotyrosine content. In
      strict contrast, administration of L-arginine 3 h after reperfusion, a time point
      when iNOS was expressed, resulted in a significant increase in myocardial NO(x)
      content, myocardial injury, and toxic peroxynitrite formation as measured by
      nitrotyrosine. CONCLUSION: Our results demonstrated for the first time that L
      arginine administered at different time points during ischemia/reperfusion
      exerted different effects on post-ischemic myocardial injury, and suggests that
      stimulation of eNOS reduces nitrative stress and decreases apoptosis whereas
      stimulation of iNOS increases nitrative stress and enhances myocardial
      reperfusion injury.

PMID- 15158151
TI  - A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in
      male spontaneously hypertensive rats.
AB  - OBJECTIVE: Sexual dimorphism has been observed in arterial hypertension. Blood
      pressure levels are lower in female than in male spontaneously hypertensive rats
      (SHR). Angiotensin II (Ang II) plays a major role in the regulation of blood
      pressure. The aim of this study was to compare Ang II vascular reactivity and
      AT(1) and AT(2) receptor gene expression in female and male SHR. METHODS: SHR
      animals were divided into four groups: (I) male, (II) female in physiological
      estrus, (III) ovariectomized and (IV) ovariectomized treated with estrogen.
      Arterial blood pressure, AT(1) and AT(2) mRNA expression were determined. Ang II
      responses in aorta and mesenteric vessels were also evaluated. RESULTS: In female
      SHR, aorta and mesenteric microvessels were hyporeactive to Ang II in comparison
      to male SHR. In ovariectomized females, Ang II vasoconstriction was similar to
      that of males. Estrogen treatment abolished this difference. The mRNA expression
      for AT(1) was higher in aorta and mesenteric vessels from males than in females.
      In ovariectomized SHR, mRNA expression for AT(1) was comparable to that of males.
      Treatment with estrogen reversed the over expression observed. Whereas AT(2) gene
      expression did not differ, a lower ratio AT(1)/AT(2) was found in female than in
      male vessels. A higher mRNA expression for AT(1) was observed in kidney from male
      than in female. Ovariectomy resulted in up-regulation of this subtype receptor.
      Treatment with estrogen reversed the overexpression. AT(2) gene expression was
      higher in kidney from female than male SHR. Ovariectomy reduced AT(2) gene
      expression and estrogen treatment reversed the alteration observed in kidney.
      CONCLUSION: There is sexual dimorphism in vascular reactivity and in receptor
      gene expression to Ang II in SHR. We conclude that estrogen modulates AT(1) and
      AT(2) receptor gene expression and that this might explain at least partially the
      lower blood pressure observed in female SHR.

PMID- 15158152
TI  - Green tea catechins inhibit neointimal hyperplasia in a rat carotid arterial
      injury model by TIMP-2 overexpression.
AB  - OBJECTIVE: Although it has been demonstrated that the antioxidant properties of
      tea catechins reduce atherosclerotic lesions in various animal models of
      hyperlipidemia, it is not yet clear whether these catechins prevent
      hyperlipidemia-independent arterial remodeling induced by balloon angioplasty. We
      evaluated the influence of the administration of the tea extract on vascular
      remodeling in a rat carotid artery balloon-injury model. METHODS AND RESULTS:
      Male Wistar rats were supplied drinking water with or without green tea extract
      (1 mg/ml) supplement. Administration of the tea extract reduced the area of the
      intima (30%) and the ratio of the intimal area to the medial area (36.2%) in
      injured arteries compared with those of control rats at 14 days after the injury.
      Real-time RT-PCR, Western blot, and gelatin zymography revealed a significant
      increase in tissue inhibitor of matrix metalloproteinase (MMP)-2 (TIMP-2)
      expression as well as a significant reduction of gelatinolytic net activity and
      activated MMP-2 levels in the injured arteries as a result of the administration
      of the tea extract compared with those of control group. Similarly,
      epigallocatechin-3-gallate, a major constituent of green tea catechins,
      significantly upregulated TIMP-2 expression in cultured smooth muscle cells.
      Immunohistochemical analysis showed that the increase of TIMP-2 protein occurred
      preferentially in the developing neointima. CONCLUSION: These results indicate
      that catechins inhibit intimal hyperplasia in a rat balloon-injury model through
      the upregulation of TIMP-2 expression to modulate MMP activity.

PMID- 15158153
TI  - Suppression of early atherosclerosis in LDL-receptor deficient mice by oral
      tolerance with beta 2-glycoprotein I.
AB  - BACKGROUND: Atherosclerosis is considered analogous to chronic inflammatory
      diseases. Beta 2-glycoprotein I (beta 2GPI) is a phospholipid binding protein
      shown to serve as a target for prothrombotic antiphospholipid antibodies. It has
      recently been demonstrated to drive an immune mediated reaction and enhance
      murine atherosclerosis. Oral tolerance is a method in which feeding a given
      antigen, downregulates the respective immune responses towards it, and attenuates
      concomitant organ specific disorders. Herein, we tested the hypothesis, that
      inhibiting cellular immunity to beta 2GPI would result in suppression of fatty
      streak formation in mice. METHODS AND RESULTS: LDL receptor deficient mice were
      fed different doses of human or bovine beta 2GPI or BSA and than switched to an
      atherogenic diet. To determine the effect of feeding on lymph node proliferative
      indices, separate groups of mice were fed beta 2GPI and then immunized with the
      respective antigen. Feeding either human or bovine beta 2GPI was effective in
      attenuating atherosclerosis as compared to control fed animals. Oral feeding with
      of beta 2GPI inhibited lymph node cell reactivity to beta 2GPI in mice immunized
      against the human protein. Oral tolerance was also capable of reducing reactivity
      to oxidized LDL in mice immunized against oxLDL. IL-4 and IL-10 production was
      upregulated in lymph node cells of beta 2GPI-tolerant mice immunized against beta
      2GPI, upon priming with the respective protein. CONCLUSION: Thus, oral
      administration of beta 2GPI is an effective means of suppressing atherogenesis in
      mice and should further be investigated.

PMID- 15158155
TI  - Expression of alpha 4 and alpha 7 nicotinic receptors in the brainstem of female
      rabbits after coitus.
AB  - Coital signaling in the female rabbit involves sequential events in the brainstem
      and hypothalamus, resulting in a massive release of hypothalamic gonadotropin
      releasing hormone (GnRH) that peaks within 1-2 h after mating. The neural
      connections between coitus and GnRH release involves norepinephrine (NE) and
      acetylcholine (ACh) since administration of antagonists against NE (dibenamine or
      phentolamine) or ACh (atropine, alpha-bungarotoxin (alpha-BTX) or scopolamine)
      blocks or attenuates ovulating events. Moreover, hypothalamic NE release and
      brainstem tyrosine hydroxylase (TH, the rate-limiting enzyme for NE synthesis)
      expression in the noradrenergic areas increase prior to, or in concert with, the
      preovulatory GnRH surge. How ACh is involved in the control of ovulation in the
      rabbit is lesser known. In the present study, the number of brainstem neurons
      expressing TH, alpha4 and alpha7 subunits of the nicotinic ACh receptor (nAChR)
      before and after coitus was determined by immunocytochemistry. Compared to non
      mated female rabbits, the number of alpha4, alpha7 and TH single-labeled neurons
      as well as alpha4/TH and alpha7/TH double-labeled neurons increased in the A1, A2
      and A6 brainstem noradrenergic areas at 1 h, but not 2 h, after coitus. The
      results suggest that the participation of ACh in the control of coitus-induced
      ovulation may include activation of alpha4beta2 and alpha7 nAChRs in neurons
      within or adjacent to the brainstem noradrenergic areas in female rabbits.

PMID- 15158154
TI  - Cathepsin S expression is up-regulated following balloon angioplasty in the
      hypercholesterolemic rabbit.
AB  - OBJECTIVE: Neointimal development following balloon angioplasty involves many
      factors including smooth muscle cell (SMC) migration and proliferation and
      extracellular matrix (ECM) remodeling. Further, in hypercholesterolemic (HC)
      conditions, there is an influx of macrophage foam cells (FCs) into the restenotic
      lesion, which also involves degradation of the basement membrane and surrounding
      ECM. The ECM remodeling that occurs during restenosis has been shown to be
      mediated by various proteases. Here we have investigated the role of cathepsin S
      (CatS), a cysteine protease, in this process. METHODS AND RESULTS: We have
      demonstrated by Taqman quantitative PCR, Western blot, and immunohistochemistry
      that CatS is up-regulated in restenotic lesions of HC rabbits following balloon
      injury of the iliofemoral artery. CatS mRNA expression was elevated 28-fold in
      balloon-injured vessels relative to uninjured contralateral vessels in HC rabbits
      8 weeks post-angioplasty (p<0.05). CatS protein expression was detected within 1
      day post-injury, persisted throughout the entire time course evaluated (60 days
      post-injury), and was co-localized with SMCs, macrophages, and FCs. In contrast,
      cystatin C (CysC), the endogenous inhibitor of cathepsins, was only minimally up
      regulated following injury. CysC mRNA expression was elevated 3.5-fold in balloon
      injured vessels relative to uninjured contralateral vessels in HC rabbits 8 weeks
      post-angioplasty (p<0.005), and up-regulation of protein expression was not
      detected until days 28 and 60 post-injury. Additional biochemical studies using
      recombinant rabbit CatS revealed that rabbit CatS digests laminin, fibronectin,
      and type I collagen. Further, CatS expression was evaluated in SMCs that were
      induced to migrate through a matrix-coated Boyden chamber upon platelet-derived
      growth factor (PDGF) stimulation. The addition of a selective CatS inhibitor
      reduced SMC migration dose-dependently with an 80% reduction in migration at 30
      nM (p<0.005). Additionally, we have shown that CatS protein expression by human
      macrophages was increased upon stimulation with oxidized low density lipoprotein
      (ox-LDL), implying augmentation of CatS production during foam cell formation.
      CONCLUSION: Taken together, our results indicate an enhanced expression of CatS
      during neointima formation and it is associated with invading SMCs, macrophages,
      and FCs, highlighting the importance of CatS in the pathogenesis of restenosis.

PMID- 15158156
TI  - Prevention of catecholaminergic oxidative toxicity by 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl and its recycling complex with polynitroxylated
      albumin, TEMPOL/PNA.
AB  - Reactive oxygen species (ROS) generated from dopamine and its oxidation products
      have been implicated in the pathogenesis and toxicity from treatment of
      Parkinson's disease-associated autonomic neuropathy, and antioxidant therapies
      have been proposed as treatment and prophylaxis for this disorder. However, many
      antioxidants are rapidly and, under physiological conditions, irreversibly
      oxidized, rendering them redox-inactive. We have examined the potential of 4
      hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl and polynitroxylated albumin
      (TEMPOL/PNA), an antioxidant complex that facilitates recycling of inactivated
      antioxidant to its redox-active form, as a protective agent against the toxicity
      of the catecholaminergic ROS generator, 6-hydroxydopamine (6-OHDA). TEMPOL/PNA is
      more effective against depression of activity level by 6-OHDA than the non
      recycling antioxidant, TEMPOL, in a murine model of catecholaminergic oxidative
      damage. TEMPOL/PNA is also less toxic than TEMPOL in mice, allowing
      administration of higher doses of antioxidant. Both TEMPOL and TEMPOL/PNA give
      rise to prevention of apoptosis and to translocation of NF-kappaB from the
      cytoplasm to the nucleus of PC12 cells treated with 6-OHDA, but in vivo,
      TEMPOL/PNA maintains redox-active blood levels of TEMPOL for almost 5 h, whereas
      administration of TEMPOL alone results in clearance of blood redox activity
      within 1 h. PNA enhances the therapeutic index of TEMPOL, and the recycling
      antioxidant that results from their adjunctive administration may prove useful in
      disorders involving oxidative stress.

PMID- 15158157
TI  - Differential presynaptic modulation of excitatory and inhibitory autaptic
      currents in cultured hippocampal neurons.
AB  - Short-term synaptic plasticity has an important role in higher cortical function.
      Hyperpolarization may effect a form of short-term plasticity by promoting
      recovery from sodium channel inactivation or by activating axonal A-type
      potassium channels. To determine whether one or both processes occur, we examined
      the effect of hyperpolarizing prepulses on autaptic currents in cultured
      postnatal rat hippocampal neurons. As expected of enhanced recovery from sodium
      channel inactivation, hyperpolarizing prepulses reversibly increased fast
      excitatory autaptic currents (eacs) mediated by alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors (AMPARs), slow eacs mediated by N-methyl-D
      aspartate receptors (NMDARs), and inhibitory autaptic currents (iacs) mediated by
      gamma-aminobutyric acidA receptors (GABAARs). Hyperpolarizing prepulses augmented
      nearly all fast and slow eacs but only half of the iacs. This change occurred
      without a change in autaptic current kinetics. Of note, hyperpolarizing prepulses
      did not significantly reduce autaptic currents in any neuron studied. The rapidly
      dissociating competitive antagonists kynurenate and L-2-amino-5-phosphonovaleric
      acid (LAPV) inhibited fast and slow eacs, respectively, to the same extent with
      and without a hyperpolarizing prepulse. In addition, hyperpolarizing prepulses
      revealed a slow eac even after the slow eac evoked without a prepulse was
      completely blocked by the open channel blocker, (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). Finally,
      hyperpolarizing prepulses did not alter currents evoked by exogenous applications
      of glutamate and GABA. These findings suggest that hyperpolarizing prepulses
      preferentially enhance eacs over iacs, and that they do so, in part, by
      overcoming conduction block or by activating silent synapses.

PMID- 15158158
TI  - Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's
      disease: linkage of poorer cognitive performance to tau pathology in forebrain.
AB  - APPsw transgenic mice bearing the "Swedish" amyloid precursor protein (APP)
      mutation and JNPL3 transgenic mice bearing the P301L (Tau) mutation were compared
      to control non-transgenic (NT) mice in an extensive behavioral test battery
      administered between 5 and 8.5 months of age. APP mice were impaired in a variety
      of cognitive-based tasks prior to overt Abeta plaque development, making
      involvement of mutant APP overexpression and/or oligomeric Abeta assemblies most
      likely. Although Tau mice, as a group, were not impaired in any single behavioral
      measure, a collective assessment of behavioral measures through discriminant
      function analysis showed that Tau mice were impaired in overall behavioral
      (cognitive) performance. Moreover, correlation analyses involving Tau mice alone
      revealed linkage between poorer cognitive performance in all three water maze
      tasks and the number of neurofibrillary tangle (NFT)-containing neurons in
      neocortex and hippocampus. These findings indicate that: (1) APP mice show early
      and extensive cognitive impairment before evident Abeta deposition, and (2) the
      process or product of NFT formation in Tau mice is sufficient to deleteriously
      impact cognitive performance.

PMID- 15158159
TI  - Transcriptional activation of p62/A170/ZIP during the formation of the
      aggregates: possible mechanisms and the role in Lewy body formation in
      Parkinson's disease.
AB  - Formation of intracellular inclusion bodies due to defects in the protein
      degradation machinery is associated with the pathogenesis of neurodegenerative
      diseases. Sequestosomal protein p62/A170/ZIP, which is an oxidative stress
      related protein and a ubiquitin-binding protein, is a component protein of Lewy
      bodies that are observed in patients with Parkinson's disease. The association of
      p62 with poly-ubiquitinated proteins may be an important step in the formation of
      intracellular protein aggregates like Lewy bodies. To study the role of p62 in
      the formation of protein aggregates in PC12 cells, we monitored the intracellular
      localizations of p62 and ubiquitinated proteins and the levels of both components
      during treatment with MG132, a proteasome inhibitor. In the early stage of
      aggregate formation, p62 did not always co-localize with ubiquitin. In contrast,
      these proteins were always co-localized in later stages. After the treatment of
      the cells with MG132, we found that the expression level of p62 increased due to
      the transcriptional activation of the gene and that higher molecular sizes of
      p62, corresponding to mono- and di-ubiquitinated formes, were also formed. Both
      the transcriptional inhibitor actinomycin D and an antisense oligonucleotide of
      p62 inhibited the MG132-mediated increase of p62, the sequestration of
      ubiquitinated proteins, and the enlargement of the aggregates. Furthermore, p62
      positive aggregates were observed primarily in surviving cells. Together, these
      results suggest that p62 plays an important role in the protection of cells from
      the toxicity of misfolded proteins by enhancing aggregate formation especially in
      the later stages.

PMID- 15158160
TI  - Traumatic brain injury increases TGF beta RII expression on endothelial cells.
AB  - Transforming growth factor beta (TGFbeta) modulates a variety of growth related
      functions following traumatic injury. The cellular response to TGFbeta is
      predominantly mediated through TGFbeta receptor I (TGFbetaRI) and receptor II
      (TGFbetaRII) on the cell surface and SMAD proteins intracellularly. We
      investigated the expression of TGFbeta receptors in the acute and chronic phases
      of a traumatic cerebral injury (TCI) by immunohistochemistry and in cultures of
      murine brain microvascular endothelial (EN) cells using cytofluorimetry. Here, we
      report that TGFbetaRII expression significantly increases on brain endothelial
      cells in the chronic phase of TCI. SMAD3 and SMAD4 protein expression were also
      upregulated suggesting the activation of TGFbeta receptor intracellular
      signaling. When TGFbetaRI and TGFbetaRII expression was studied in in vitro
      cultures of murine brain microvessel EN cells, TGFbetaRII showed increased
      expression on proliferating cells that are incorporating BrdU. These data show a
      differential expression of TGFbetaRI and TGFbetaRII on brain microvessel EN cells
      in the acute and chronic phases of TCI that might be associated with EN
      proliferation following injury.

PMID- 15158161
TI  - Magnetic resonance spectroscopic analysis of Alzheimer's disease mouse brain that
      express mutant human APP shows altered neurochemical profile.
AB  - Transgenic mice that express mutant human amyloid precursor protein (APPTg2576)
      develop beta-amyloid (Abeta) plaques throughout the cortex starting at 10-12
      months of age. We examined the neurochemical profile of APPTg2576 mice using in
      vitro and in vivo magnetic resonance spectroscopy (MRS); gross abnormalities
      using magnetic resonance imaging (MRI) and plaque distribution; size and number
      using immunohistochemistry. Transgenic mice were anesthetized with halothane and
      scanned at 4.7 T using T2-weighted imaging and in vivo MRS of frontal cortex. In
      vitro MRS was run from brain extracts of frontal cortex in both APP and wild-type
      mice. Mice were also perfused and brains were collected and cut for
      immunohistochemistry. We found that N-acetylaspartate (NAA), glutamate and
      glutathione were decreased by 17%, 22% and 36%, respectively, in the cerebral
      cortex of APP transgenic mice at 19 months of age when Abeta deposits are
      widespread. Taurine was increased 21% compared to wild-type. Decreased levels of
      NAA and increased levels of taurine are consistent with decreased neuronal
      viability and increased glial volume, and are similar to findings of decreased
      NAA and increased myo-inositol in human Alzheimer's disease (AD) brains.
      Correlation between the severity of Abeta deposition and altered neurochemical
      profile remains to be studied. Nevertheless, the altered neurochemical profile
      may be a valuable marker to test therapeutics in this mouse model.

PMID- 15158162
TI  - Neonatal neurosteroid administration alters parvalbumin expression and neuron
      number in medial dorsal thalamus of adult rats.
AB  - The neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone)
      is a potent endogenous modulator of GABAA receptor function. A single neonatal
      allopregnanolone administration (10 mg/kg, i.p.) was previously shown to alter
      the localization of parvalbumin-positive neurons in the prefrontal cortex at
      maturity. Cells in the prefrontal cortex receive the majority of their inputs
      from the medial dorsal nucleus of the thalamus. We investigated whether neonatal
      allopregnanolone administration alters the neuronal population of the medial
      dorsal nucleus of the thalamus. We show that the number of parvalbumin-expressing
      neurons is increased while the total neuron number is decreased in the medial
      dorsal nucleus after allopregnanolone administration. EAAT3 (excitatory amino
      acid transporter type 3, the neuron-specific glutamate reuptake transporter)
      immunoreactivity was unchanged in adjacent sections. These findings suggest that
      neonatal allopregnanolone administration disrupts the normal development of the
      prefrontal cortex and medial dorsal thalamus, indicating that neurosteroid levels
      are important for proper development of thalamocortical systems and may play a
      role in neurodevelopmental disorders such as schizophrenia.

PMID- 15158163
TI  - TorsinA negatively controls neurite outgrowth of SH-SY5Y human neuronal cell
      line.
AB  - Early onset generalized dystonia is a severe form of primary dystonia linked to a
      mutation of the DYT1(TOR1A) gene on chromosome 9q34. DYT1 gene codifies for human
      torsinA, an AAA+ ATPase associated with the membranes of endoplasmic reticulum
      (ER) and the synaptic vesicles and proposed to be involved in trafficking of
      tubular-vesicular membrane through neuronal processes. In this study, the
      presence and the intracellular distribution of torsinA protein in SH-SY5Y
      neuroblastoma cells were evaluated by immunofluorescence and Western blot
      analysis following differentiation with retinoic acid and BDNF. Protein
      expression was then inhibited by transient antisense transfection and the
      possible effect on neurite outgrowth was observed. In SH-SY5Y cells torsinA, with
      an apparent MW of 38 kDa, is endogenously present and distributed, with a
      punctate pattern, in the cytosol and along the neurites. The protein showed high
      intensity of immunoreactivity in the neurite varicosities and was partially co
      localized with vesicles markers. Terminally differentiated cells showed an
      increase of protein expression. Oligonucleotide antisense treatment induced a
      significant response to differentiating stimuli, lead to sprouting of longer
      neurites and increase in growth cone areas. A relationship between torsinA and
      tau protein, which is involved in axon elongation and establishment of neuronal
      polarity, was demonstrated by co-immunoprecipitation experiments. These findings
      suggest that torsinA, throughout the interaction with microtubule associated
      proteins, may contribute to control neurite outgrowth and could be involved in
      maintaining cell polarity.

PMID- 15158164
TI  - Substance P inhibits potassium and calcium currents in inner ear spiral ganglion
      neurons.
AB  - Substance P (SP), a member of the tachykinin family of neurotransmitters and
      neuromodulators, has been identified on spiral ganglion neurons (SGNs) in the
      inner ear; however, its high affinity receptor, neurokinin-1 (NK1), has not been
      identified and the physiological effects of SP on SGNs are not well understood.
      To address these issues, immunolabeling, RT-PCR, Western blots and whole-cell
      patch-clamp recordings were made from SGNs in P0-P5 mouse cochlear organotypic
      cultures. The NK1 receptor was detected on SGNs by immunocytochemistry, the
      protein was detected in cochlear tissues by Western blots, and the mRNA for the
      NK1 receptor was also found in cochlear tissues of postnatal mice (P2) by RT-PCR.
      Application of SP (1 to 25 microM) significantly increased the latency of SGN
      action potentials (APs) (mean increase 7.8 +/- 4 ms; 25 microM of SP), prolonged
      the duration of the action potential and made the resting potential (RP) more
      positive (mean 9.0 +/- 7 mV) relative to normal values (-54 +/- 6 mV). SP (1 to
      25 microM) also suppressed voltage-activated potassium currents (IK+) and calcium
      currents (ICa2+). Puffing 25 microM of SP onto SGNs suppressed IK+ by 43 +/- 9%
      (n = 7) and ICa2+ by 40.6 +/- 5.6% (n = 7); both currents recovered when SP was
      washed out. A SP antagonist blocked the SP-induced suppression of IK+ and ICa2+.
      These results indicate that SP acting through NK1 receptors can have direct
      neuromodulatory effects on SGNs.

PMID- 15158165
TI  - Inhibition of pyruvate kinase activity by cystine in brain cortex of rats.
AB  - Cystinosis is a metabolic disturb associated with excessive lysosomal cystine
      accumulation secondary to defective cystine efflux. Patients affected by this
      disease develop a variable degree of symptoms depending of the involved tissues.
      Accumulation of cystine in the brain may lead to severe neurological symptoms.
      However, the mechanisms by which cystine is neurotoxic are not fully understood.
      Considering that pyruvate kinase (PK) is a thiolic enzyme crucial for the
      glycolytic pathway, and disulfides like cystine may alter thiolic enzymes by
      thiol/disulfide exchange, the main objective of the present study was to
      investigate the effect of cystine on PK activity in the brain cortex of
      developing Wistar rats. We also performed kinetic studies and investigated the
      effects of GSH, a biologically occurring thiol groups protector, and cysteamine
      (CysN), the drug used for cystinosis treatment, on the enzyme activity. We
      observed that cystine inhibited the enzyme activity by two different mechanisms,
      one through the competition with ADP and phosphoenolpyruvate (PEP), and the other
      non-competitively, probably through oxidation of the thiol groups of PK. We also
      observed that GSH and cysteamine fully prevented and reversed the inhibition
      caused by cystine. Considering that cysteamine is used in patients with
      cystinosis because it causes parenkimal organ cystine depletion, the present data
      provides a possible new beneficial effect for the use of this drug.

PMID- 15158166
TI  - The biogenic trace amine tyramine induces a pronounced hydroxyl radical
      production via a monoamine oxidase dependent mechanism: an in vivo microdialysis
      study in mouse striatum.
AB  - Tyramine is a biogenic trace amine that releases monoamines and is a good
      substrate for monoamine oxidase (MAO)-A/B. Here we investigated whether tyramine
      affects hydroxyl radical formation in the intact and lesioned dopaminergic
      system. Male C57bl/6 mice received systemic and local tyramine administrations.
      Hydroxyl radical formation and dopamine (DA) overflow were determined in the
      striatum using in vivo microdialysis in combination with the salicylate
      hydroxylation assay. Systemic injection of tyramine neither enhanced
      extracellular dopamine nor induced hydroxyl radical formation. In contrast, when
      tyramine was incorporated into the dialysate fluid, hydroxyl radical formation
      and extracellular dopamine levels were significantly enhanced. Systemic
      pretreatment with the MAO-A/B inhibitor tranylcypromine or with the dopaminergic
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly
      diminished the tyramine-induced hydroxyl radical formation by 73.1% and 80.6%,
      respectively. We conclude that the mechanism of tyramine-induced hydroxyl free
      radical formation involves MAO metabolism and requires an intact dopaminergic
      system. Pharmacological intervention on the MAO-mediated formation of hydroxyl
      free radicals seems to be a promising strategy to prevent oxidative damage in the
      nigrostriatal dopaminergic system.

PMID- 15158167
TI  - Amphetamine-induced behavioral activation is associated with variable changes in
      basal ganglia output neurons recorded from awake, behaving rats.
AB  - Systemic or intra-striatal administration of d-amphetamine (AMPH) elicits a dose
      dependent pattern of behavioral activation and neuronal firing in the striatum.
      To determine if the AMPH-induced striatal firing pattern is expressed in the
      substantia nigra pars reticulata (SNr), a main target of striatal efferents and
      the primary output nucleus of the basal ganglia, we recorded the activity of 214
      SNr units in alert, behaving rats responding to either systemic (1.0 or 5.0
      mg/kg, sc) or intra-striatal (20 microg/microl/min) AMPH. Both routes of
      administration increased behavior but the strongest effects occurred after
      systemic injection. A dose of 1.0 mg/kg progressively increased locomotion, head
      movements, and sniffing, whereas after 5.0 mg/kg behavioral responding became
      progressively more focused and stereotyped. The collective response of SNr
      neurons was a net increase in firing rate that was most apparent after the low
      systemic dose and intra-striatal infusion. Further analysis revealed significant
      unit populations that were either excited, inhibited or showed no change.
      Although excitations predominated over inhibitions in all cases, a sizable
      population of units was unresponsive: approximately 25% to systemic AMPH and
      almost half to intra-striatal infusion. Subsequent injection of haloperidol (0.5
      or 1.0 mg/kg, sc), a dopamine receptor antagonist, reversed both the behavioral
      and electrophysiological effects of AMPH. Thus, as in striatum, dopamine appears
      to play a critical role in AMPH-induced changes in SNr activity. Interestingly,
      however, SNr activity did not closely parallel the striatal response, suggesting
      that patterns of neuronal responding to AMPH in striatum are not reliably relayed
      to SNr.

PMID- 15158168
TI  - Repeated cocaine injections have no influence on tyrosine hydroxylase activity in
      the rat nucleus accumbens core or shell.
AB  - Numerous reports have demonstrated augmented cocaine-evoked release of dopamine
      in the nucleus accumbens of rats pre-treated with cocaine. However, the extent to
      which repeated cocaine injections affect basal levels of dopamine is unclear.
      There have been reports of increases, decreases, or no change in basal levels of
      extracellular accumbal dopamine resulting from repeated psychostimulant
      administration. The present study assessed the activity of tyrosine hydroxylase,
      the rate-limiting enzyme in dopamine synthesis, in the nucleus accumbens
      following either acute or repeated cocaine administration. The in vivo
      microdialysis technique was used to measure accumulation of the dopamine
      precursor DOPA following intra-accumbal administration of the DOPA decarboxylase
      inhibitor NSD 1015 through the microdialysis probe. This method provides an
      estimate of tyrosine hydroxylase activity within the nucleus accumbens. Results
      indicate that neither acute nor repeated cocaine administration produced any
      change in DOPA accumulation in either the nucleus accumbens shell or core. These
      data indicate that dopamine synthesis is not altered by cocaine administration.

PMID- 15158169
TI  - Cortical control of generalized absence seizures: effect of lidocaine applied to
      the somatosensory cortex in WAG/Rij rats.
AB  - The role of the somatosensory cortex (SmI) in the incidence of spike-wave
      discharges (SWDs) was studied in a genetic model of absence epilepsy, WAG/Rij
      rats. SWDs were recently shown to initiate at the perioral area of the SmI and
      spread over the cortex and thalamus within a few milliseconds [J. Neurosci. 22
      (2002) 1480]. It was hypothesized that functional deactivation of the SmI might
      reduce the appearance of SWDs. This was tested using unilateral microinjections
      (1 microl) of 2% lidocaine into the SmI in 13 WAG/Rij rats. Electrocorticogram
      (ECoG) was recorded in free moving animals from four cortical sites after
      lidocaine and control (saline) injections. Lidocaine effectively diminished the
      power of the ECoG spectra mostly in the area surrounding the injection site.
      Deactivation of the perioral region of the SmI reduced the incidence of SWDs at
      the entire cortex in both hemispheres. The number of SWDs gradually reached
      control level at the end of the second hour after injections of lidocaine. These
      data show that proper functioning of SmI is important for the occurrence of SWDs,
      supporting the idea that absence seizures might have a focal cortical origin.

PMID- 15158170
TI  - Lamina-selective changes in the density of synapses following perturbation of
      monoamines and acetylcholine in the rat medial prefrontal cortex.
AB  - The rat medial prefrontal cortex is known to have diverse brain functions such as
      learning and memory, attention, and behavioral flexibility. Although these
      functions are affected by monoamines (dopamine (DA), noradrenaline (NA) and
      serotonin (5-HT)) and acetylcholine (ACh), the detailed mechanisms remain
      unclear. These neuromodulators also have effects on synapse formation and
      maintenance, and regulate plasticity in the central nervous system (CNS). To
      clarify the effects of these neuromodulators on changes in the density of
      synapses in the rat medial prefrontal cortex, we separately administered a D1- or
      D2-antagonist, NA neurotoxin, 5-HT synthetic inhibitor, or muscarinic ACh
      antagonist for 1 week, and counted the number of synapses on electron microscopic
      photographs taken from the prelimbic area of the medial prefrontal cortex. The
      density of synapses in lamina I was regulated by DA via D1-like receptors, and
      that in laminae II/III was decreased by depletion of NA or ACh. However, 5-HT did
      not have a regulatory effect on the synaptic density throughout the layers in
      this brain region. The data in this study and our previous studies indicate that
      there are appreciable regional differences in the magnitude of biogenic amine
      mediated synaptic plasticity in the rat CNS. These neuromodulators may have a
      trophic-like effect on the selected neuronal circuit to maintain synaptic
      contacts in the rat CNS. The synaptic density in the medial prefrontal cortex
      regulated by monoamines and ACh could be important not only for synaptic
      plasticity in this region but also for pharmacotherapeutic drug treatment.

PMID- 15158171
TI  - Differential modulation of withdrawal reflexes by a cannabinoid in the rabbit.
AB  - Inhibition of spinal and trigeminal withdrawal reflexes by morphine and by the
      cannabinoid agonist HU 210 has been studied in anaesthetized and in decerebrated
      rabbits. In intact, pentobarbitone-anaesthetized animals, the jaw-depressor
      reflex (JDR) evoked by stimulation of the tongue, and the reflex elicited in the
      ankle flexor tibialis anterior (TA) by stimulation of the toes were inhibited to
      the same extent by morphine (1-30 mg kg(-1) i.v. cumulative). In spinalized,
      anaesthetized rabbits morphine depressed the JDR to the same level as in non
      spinal preparations, but the effect of the opioid on the TA reflex was
      significantly reduced. All effects of morphine were reversed by naloxone (0.25 mg
      kg(-1), i.v.). In anaesthetised intact animals, HU 210 depressed the JDR at a
      dose of 100 nmol kg(-1) i.v. cumulative, reduced reflexes evoked in the knee
      flexor muscle semitendinosus (ST) by stimulation at the toes at a dose of 30 nmol
      kg(-1) i.v. cumulative, but had no consistent or significant effects on the TA
      reflex to toe stimulation. The same results were obtained in spinalized,
      anaesthetised animals. In decerebrated, spinalized rabbits with no anaesthesia,
      HU 210 (30 nmol kg(-1)) depressed both ST and TA reflexes evoked by toe
      stimulation. These data reveal that trigeminal and spinal withdrawal reflexes are
      equally sensitive to morphine provided the spinal cord is intact, suggesting that
      at least part of the action of systemic morphine is due to activation of
      descending inhibition. The present results also show for the first time that
      cannabinoid agonists can inhibit trigeminal withdrawal reflexes. HU 210 had
      differential effects on the three reflexes studied depending on the presence or
      absence of anaesthesia. This is the first occasion on which we have found
      pharmacological distinctions between withdrawal reflexes, and indicates that
      spinal sensorimotor processing is more heterogeneous than has been suspected
      previously.

PMID- 15158172
TI  - Human acupuncture points mapped in rats are associated with excitable muscle/skin
      nerve complexes with enriched nerve endings.
AB  - As part of our ongoing investigation into the neurological mechanisms of
      acupuncture, we have tried to correlate the distribution of afferent nerve
      endings with acupuncture points (AP) in the rat hind limbs. In vivo extracellular
      microfilament recordings of Aalpha/Abeta/Adelta fibers were taken from peripheral
      nerves to search for units with nerve endings or receptive fields (RF) in the
      skin or the muscles. The location of the RFs for each identified unit was marked
      on scaled diagrams of the hind limb. Noxious antidromic stimulation-induced Evans
      blue extravasation was used to map the RFs of C-fibers in the skin or muscles.
      Results indicate that, for both A- and C-fibers, the distribution of RFs was
      closely associated with the APs. In the skin, the RFs concentrate either at the
      sites of APs or along the orbit of meridian channels. Similarly, the majority of
      sarcous sensory receptors are located at the APs in the muscle. Results from our
      studies strongly suggest that APs in humans may be excitable muscle/skin-nerve
      complexes with high density of nerve endings.

PMID- 15158173
TI  - Failure of gamma-hydroxybutyric acid both to increase neuroactive steroid
      concentrations in adrenalectomized-orchiectomized rats and to induce tolerance to
      its steroidogenic effect in intact animals.
AB  - Gamma-Hydroxybutyric acid (GHB), a drug proposed in the treatment of alcohol
      withdrawal syndrome, increases the cerebrocortical and plasma concentrations of
      the neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone
      (THDOC). In the present study, we examined the role of hypothalamic-pituitary
      adrenal (HPA) axis in the effect of GHB by measuring the concentrations of these
      steroids in the brain and plasma of adrenalectomized-orchiectomized (Adx-Orx)
      rats. The acute administration of GHB (500 mg/kg, i.p.) induced in 30 min an
      increase in the concentrations of allopregnanolone, THDOC and their precursors
      pregnenolone and progesterone in different brain areas (cerebral cortex,
      hypothalamus and cerebellum) and plasma of sham-operated rats but had no effect
      on the concentrations of these compounds in Adx-Orx rats, suggesting that
      activation of the HPA axis mediates the effect of GHB on brain and plasma
      concentrations of neuroactive steroids. Moreover, we evaluated whether repeated
      exposure of GHB induces tolerance to its steroidogenic effects. Chronic
      administration of GHB (500 mg/kg, i.p., twice a day for 10 days) to intact
      animals failed to affect the levels of progesterone, allopregnanolone, or THDOC
      measured 3 or 48 h after the last drug administration, whereas a challenge
      injection of GHB or ethanol was still able to increase the concentrations of
      these steroids in brain and plasma. These results indicate that repeated exposure
      to GHB fails to induce tolerance or cross-tolerance to the steroidogenic action
      of GHB or ethanol, respectively.

PMID- 15158174
TI  - Comparison of the effect of TAK-147 (zanapezil) and E-2020 (donepezil) on
      extracellular acetylcholine level and blood flow in the ventral hippocampus of
      freely moving rats.
AB  - The effects of zanapezil (TAK-147) and donepezil (E2020) on extracellular
      acetylcholine (ACh) levels were investigated by HPLC-microdialysis of ventral
      hippocampus (VH) in freely moving intact rats. The results showed that the basal
      ACh release rate in the VH is 116.7 +/- 12.4 to 158.4 +/- 22.86 fmol/20 microl.
      At 2, 5 and 10 mg/kg, single p.o., each drug increased ACh level by 9.4%, 106.5%,
      50.8% (TAK-147) and 14.8%, 76.1%, 120.94% (E2020), respectively. The ED50 values
      were 4.52 mg/kg (1.43 - 14.29; R=0.52) and 4.07 mg/kg (1.77 - 9.37; R=0.985) for
      TAK-147 and E2020, respectively. Analysis of data revealed that the relative TAK
      147/E2020 potency ratio is 0.773, but the effect of E2020 was accompanied by more
      prominent skeletal muscle fasciculation, gnawing, increased defecation and to
      lesser extent salivation. Moreover, the significant effect of TAK-147 was
      observed earlier (20 min) than E2020 (60 min). In this study, we also
      investigated the effect of both drugs at dose of 5 mg/kg p.o. on blood flow in
      the VH using Laser Doppler Flowmetry. The results showed that the average blood
      flow rate in the VH is 6.5 +/- 0.9 ml/min/100 g. TAK-147 did not change blood
      flow, but E2020 increased blood flow in a biphasic manner. The first increment
      was obtained between 5 and 40 min (11.5 +/- 2.2 to 12.7 +/- 2.2 ml/min/100 g),
      and the second one 80-105 min (10.7 +/- 1.6 to 13.4 +/- 3.6 ml/min/100 g). In
      conclusion, the present results indicate that both TAK-147 and E2020 increase ACh
      level in the VH. E2020 showed greater potency than TAK-147, but it induced more
      fasciculation and other side effects than TAK-147. Moreover, the blood flow
      increasing properties of E2020 could be beneficial in some patients with
      Alzheimer' disease especially those with chronic vascular dementia, but at the
      same time, it could also indicate less specific ACh increasing activity than TAK
      147 and higher risk of cerebral hemorrhage. On the other hand, the fast and
      specific effect of TAK-147 may be useful for cure of early stages of Alzheimer's
      disease (AD).

PMID- 15158175
TI  - Astrocytes contribute to regulation of extracellular calcium and potassium in the
      rat cerebral cortex during spreading depression.
AB  - This study used spreading depression (SD), which is characterized by
      redistribution of ions, to examine the role of astrocytes in the regulation of
      extracellular potassium ([K+]o) and calcium ([Ca2+]o) levels. Recurrent spreading
      depression episodes were induced by application of 3 M potassium chloride to the
      cortex of adult anesthetized rats while monitoring the extracellular direct
      current (DC) potential shifts and changes in [K+]o or [Ca2+]o 6-7 mm away. The
      reversible glial toxins, fluorocitrate (FC) and fluoroacetate (FA), were injected
      locally into the cortex at doses that are selective for reducing glial function.
      The peak changes and area under the curve for [K+]o and [Ca2+]o, recovery rate
      for [K+]o, and interval between spreading depression episodes were measured
      before and at various times after administration of the toxins. Both
      fluorocitrate and fluroacetate slowed the recovery of the [K+]o and altered the
      recovery of the [Ca2+]o. Local injection of glutamate uptake inhibitors or barium
      had no effect on the peak changes in [K+]o or the rate of recovery of the [K+]o.
      The slowing of the recovery rate is consistent with the hypothesis that glial
      cells play a role in the return of [K+]o to baseline after spreading depression
      in the cortex in vivo. The change in movement of calcium after administration of
      FC suggests that astrocytes normally extrude calcium during spreading depression,
      resulting in rapid recovery of the levels of [Ca2+]o with an overshoot. These
      findings demonstrate that astrocytes contribute to the regulation of both
      potassium and calcium during and after a stress to the ionic homeostatic
      mechanisms.

PMID- 15158176
TI  - Cross reactivity of polyclonal GFAP antiserum: implications for the in-vitro
      characterisation of brain endothelium.
AB  - Following a recent claim, based on glial acidic fibrillary protein (GFAP)
      expression, that brain-derived astrocytes in culture are in fact endothelial
      cells, we immuno-labelled primary cultures of rat brain astrocytes and
      endothelium with various GFAP antisera. Both cell types stained positively with a
      polyclonal antibody, although monoclonal antiserum labelled only astrocytes. We
      conclude that staining of endothelial cells with the polyclonal GFAP antiserum is
      due to cross reactivity with another protein.

PMID- 15158177
TI  - HIV secreted protein Tat prevents long-term potentiation in the hippocampal CA1
      region.
AB  - HIV-associated dementia (HAD) is a complication of advanced HIV disease. Both
      viral products and host cytokines are believed to be involved in the pathogenesis
      of HIV-associated neurological manifestations. Among the viral products released
      by HIV-infected cells is the soluble protein Tat. We investigated the effect of
      exposure of organotypic hippocampal slices to 100 nM recombinant Tat 1-86 on long
      term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) at
      Schaffer collateral/commissural fiber-CA1 synapses. Exposure to Tat 1-86
      prevented the induction of LTP without affecting post-tetanic potentiation. Tat 1
      72delta31-61, which lacks the neurotoxic domain of Tat, had no significant effect
      on LTP. Tat's ability to disrupt synaptic plasticity may be relevant to the
      pathogenesis of the cognitive impairments seen in patients with HIV disease.

PMID- 15158178
TI  - Interleukin-18 stimulates synaptically released glutamate and enhances
      postsynaptic AMPA receptor responses in the CA1 region of mouse hippocampal
      slices.
AB  - The present study examined the effects of the proinflammatory cytokine
      interleukin-18 (IL-18) on mouse hippocampal synaptic transmission. IL-18 (100
      ng/ml) significantly increased amplitude and frequency of alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA) receptor-mediated miniature excitatory
      postsynaptic currents (AMPA-mEPSCs), that are monitored from CA1 pyramidal
      neurons of mouse hippocampal slices. IL-18 (100 ng/ml) enhanced slope of basal
      field excitatory postsynaptic potentials (fEPSPs) that are recorded from the CA1
      region of mouse hippocampal slices. There was no significant difference in the
      expression of Schaffer collateral/CA1 long-term potentiation (LTP) between in the
      presence and absence of IL-18, although IL-18 tended to inhibit saturation levels
      of the potentiation induced by tetanic stimulation in a dose-dependent manner at
      concentrations ranged from 10 ng/ml to 1 microg/ml. Paired-pulse facilitation in
      the presence of IL-18 (100 ng/ml) was not influenced after tetanic stimulation,
      while that in the absence of IL-18 was depressed. The results of the present
      study, thus, suggest that IL-18 stimulates synaptically released glutamate and
      enhances postsynaptic AMPA receptor responses in CA1 pyramidal neurons of mouse
      hippocampal slices, thereby facilitating basal hippocampal synaptic transmission
      without affecting the LTP.

PMID- 15158179
TI  - Peripheral cuing by abrupt-onset cues: the influence of color in S-R
      corresponding conditions.
AB  - Research on visuospatial attention indicates that a peripheral abrupt-onset cue
      at target position (valid condition) facilitates processing of the target,
      whereas a cue at another position interferes. This validity effect seems to be
      contingent on a similarity of the cue's color to the set of target colors (cf. J.
      Exp. Psychol.: Human Percep. Perform. 18 (1992) 1030). In Experiments 1-3, we
      confirm this contingency with cues that have the potential to activate responses.
      Thus, attentional capture and response capture are apparently governed by the
      same principle. In Experiment 2, it is demonstrated that color priming is not
      responsible for the contingency. In Experiment 3, it is shown that a more
      efficient reallocation of attention after color-dissimilar cues than after color
      similar cues might contribute to the contingency.

PMID- 15158180
TI  - The effects of aging on location-based and distance-based processes in memory for
      time.
AB  - Retrieving when an event occurred may depend on an estimation of the age of the
      event (distance-based processes) or on strategic reconstruction processes based
      on contextual information associated with the event (location-based processes).
      Young and older participants performed a list discrimination task that has been
      designed to dissociate the contribution of both types of processes. An adapted
      Remember/Know/Guess procedure [Can. J. Exp. Psychol. 50 (1996) 114] was developed
      to evaluate the processes used by the participants to recognize the stimuli and
      retrieve their list of occurrence. The results showed that aging disrupts
      location-based processes more than distance-based processes. In addition, a
      limitation of speed of processing and working-memory capacities was the main
      predictor of age-related differences on location-based processes, whereas working
      memory capacities mediated partly age differences on distance-based processes.

PMID- 15158181
TI  - The effect of a reason's truth-value on the judgment of a fallacious argument.
AB  - Informal reasoning fallacies are arguments that are psychologically persuasive
      but not valid. In the context of informal reasoning fallacies, the truth-value of
      the reason in support of a given claim is irrelevant to judging the validity of
      the argument as a whole. This property stands in sharp contrast with the general
      role of the reason's truth-value in judging arguments in general. The aim of this
      study was to test the hypothesis that in the context of informal reasoning
      fallacies the truth-value of a reason influences pupils' judgment of the extent
      to which the reason supports the claim. The results of the study confirm the
      research hypothesis.

PMID- 15158182
TI  - Action priming by briefly presented objects.
AB  - Three experiments investigated how visual objects prime the actions they afford.
      The principal concern was whether such visuomotor priming depends upon a
      concurrent visual input--as would be expected if it is mediated by on-line dorsal
      system processes. Experiment 1 showed there to be essentially identical
      advantages for making afforded over non-afforded responses when these were made
      to objects still in view and following brief (30 or 50 ms) object exposures that
      were backward masked. Experiment 2 showed that affordance effects were also
      unaffected by stimulus degradation. Finally, Experiment 3 showed there to be
      statistically equal effects from images of objects and their names. The results
      suggest that an active object representation is sufficient to generate affordance
      compatibility effects based on associated actions, whether or not the object is
      concurrently visible.

PMID- 15158183
TI  - Abilities and strategies of blind and sighted subjects in visuo-spatial imagery.
AB  - An active visuo-spatial memory task was used in order to determine the
      characteristics of mental imagery in subjects with and without visual experience.
      Subjects were instructed to generate a mental representation of verbally
      presented 2D patterns that were placed in a grid and to indicate how many pattern
      elements were in corresponding positions in the two halves of the grid according
      to a specific grid axis (vertical or horizontal). Unexpectedly, results showed a
      similar performance in early blind, late blind and sighted subjects. However,
      subjects' debriefing showed that the three groups used different strategies. The
      sighted and the late blind subjects took advantage of a visuo-spatial strategy.
      They generated a mental image of the matrix and they simplified this image to
      maintain only the relevant information in memory. In contrast, the early blind
      subjects encoded each pattern element by its location in a (X,Y) coordinate
      system without visual representation. This indicates that both early and late
      blind subjects are able to perform an active visuo-spatial imagery task as well
      as sighted subjects although they use different strategies.

PMID- 15158184
TI  - Interaction of pathogenic bacteria with rabbit appendix M cells: bacterial
      motility is a key feature in vivo.
AB  - Rabbit appendix consists mainly of lymphoid follicles (LF) covered by M cells,
      the specialized antigen-sampling cells of the mucosal immune system, and
      surrounded by glandular epithelium. Until now, these M cells have been
      characterized morphologically and histologically by using cellular markers. Here,
      the adhesion and transport of pathogenic bacteria were investigated to assess the
      function of M cells of the appendix. We used the enteroinvasive motile Salmonella
      typhimurium and the rabbit enteropathogenic non-motile Escherichia coli RDEC-1,
      which are known to target specifically rabbit M cells of Peyer's patches (PPs).
      We found that S. typhimurium efficiently attached and was transported through
      appendix M cells in vivo. In contrast to S. typhimurium, RDEC-1 targeted M cells
      only ex vivo, when bacteria were allowed to have direct contact with the surface
      of the follicle. The difference in interaction of the two bacteria with appendix
      M cells led us to investigate whether this could be correlated with the lack of
      motility of RDEC-1. We used an aflagellate mutant of S. typhimurium and found
      that it had the same infection phenotype as RDEC-1. Gene complementation restored
      the efficiency of infection to that of S. typhimurium wild-type strain. In
      conclusion, we show that M cells of the appendix display features of the
      canonical M cells of PP, since they efficiently sample luminal pathogenic
      bacteria. However, due to the morphology of the appendix, motile bacteria appear
      to be more potent in their interactions with appendix M cells.

PMID- 15158185
TI  - T-box transcription-factor-deficient mice display increased joint pathology and
      failure of infection control during staphylococcal arthritis.
AB  - To study the impact of T-box transcription factor (T-bet) on initiation and
      progression of Staphylococcus aureus sepsis and arthritis, T-bet-deficient mice
      (T-bet(-/-)) and their wild-type controls (T-bet(+/+)) were intravenously
      inoculated with 8 x 10(6) S. aureus. Already 48 h after inoculation of S. aureus,
      T-bet-deficient mice displayed increased frequency (62% versus 19%, P = 0.002) as
      well as severity of arthritis compared with wild-type controls. The bacterial
      counts were significantly increased in T-bet(-/-) mice compared with T-bet(+/+)
      as measured in kidneys 72 h after the inoculation (4.3 +/- 1.8 x 10(7) versus 3.2
      +/- 3.2 x 10(6) colony-forming units (CFU); P = 0.003). As expected, T-bet
      deficient mice displayed significantly decreased production of IFN-gamma (10-15
      fold) at 24 and 72 h after bacterial inoculation compared with wild-type mice.
      Interestingly, in the absence of T-bet, serum IL-4 was decreased at 24 h. IL-6
      did not differ at early stage of infection but was sixfold increased in T-bet(-/
      ) mice over T-bet(+/+) animals at 72 h postinoculation. Ten days after the
      inoculation, T-bet(-/-) mice still displayed significantly more pronounced weight
      loss and increased serum IL-6 levels, probably due to increased bacterial burden
      compared with T-bet(+/+) mice. The cumulative mortality was 19% in T-bet mice
      (5/27) and 0% (0/27) in control animals (P = 0.05). In conclusion, T-bet plays an
      important role in early response to S. aureus infection, protecting against
      bacterial accumulation, cachexia and septic death. Furthermore T-bet
      downregulates joint inflammation in the early phase of disease.

PMID- 15158186
TI  - Induced expression of the antimicrobial peptide melittin inhibits experimental
      infection by Mycoplasma gallisepticum in chickens.
AB  - The in vivo action of the antimicrobial peptide melittin, expressed from a
      recombinant plasmid vector, on chickens experimentally infected with Mycoplasma
      gallisepticum was studied. The plasmid vector pBI/mel2/rtTA includes the melittin
      gene under the control of an inducible tetracycline-dependent human
      cytomegalovirus promoter and the gene coding for the trans-activation protein
      rtTA. Aerosol administration of the vector, followed by infecting the chickens
      with M. gallisepticum 1226, is shown to inhibit development of infection. The
      inhibitory action was confirmed by a complex of clinical, pathomorphological,
      histological and serological studies, and also by comparing the M. gallisepticum
      reisolation frequency from the respiratory tract and internal organs. The data
      suggest that plasmid vectors expressing genes of antimicrobial peptides can be
      considered as potential agents for the prevention and treatment of mycoplasma
      infections in poultry farming.

PMID- 15158187
TI  - Toll-like receptor 2 is dispensable for acquired host immune resistance to
      Candida albicans in a murine model of disseminated candidiasis.
AB  - Previous work by our group showed that Toll-like receptor 2 (TLR2) is essential
      for activation of innate immunity, playing a major role in the response of
      macrophages to Candida albicans, triggering cytokine and chemokine expression,
      and therefore TLR2 -/- mice are more susceptible to systemic primary candidiasis.
      In this work, we used a murine model of systemic C. albicans infection, in which
      resistance to reinfection with virulent wild-type cells is induced by prior
      exposure of mice to a low-virulence agerminative strain of C. albicans (primary
      sublethal infection), to study the influence of TLR2 gene deletion on (i) the
      ability to develop an acquired resistance upon vaccination; (ii) the development
      of the acquired humoral response; and (iii) the production of Th1 cytokines IFN
      gamma, IL-12 and TNF-alpha. Our results indicate that, although TLR2 -/- mice
      have a very impaired production of Th1 cytokines compared with control mice, they
      are equally capable of mounting a specific humoral response to the fungus and
      developing a vaccine-induced resistance.

PMID- 15158188
TI  - Binding of laminin to Paracoccidioides brasiliensis induces a less severe
      pulmonary paracoccidioidomycosis caused by virulent and low-virulence isolates.
AB  - The pathogenic fungus Paracoccidioides brasiliensis is the causative agent of
      paracoccidioidomycosis (PCM). This pulmonary mycosis, acquired by inhalation of
      airborne propagules, may disseminate to several internal organs and tissues,
      leading to severe disease. Adhesion to host cell components is the first step
      involved in dissemination of pathogens. Previous studies showed that laminin, the
      most abundant glycoprotein of the basement membrane, binds to P. brasiliensis
      yeast cells, enhancing their pathogenicity in the hamster testicle model. As PCM
      is primarily a pulmonary infection, we studied the influence of previous
      treatment of yeast cells with laminin on the course of the intratracheal
      infection of resistant and susceptible mice using high-virulence (Pb18) and low
      virulence (Pb265) P. brasiliensis isolates. Laminin treatment did not alter
      fungal loads, delayed-type hypersensitivity reactions, levels of pulmonary
      cytokines and production of specific antibodies in any group of Pb18-infected
      mice. However, early in the infection, a less intense inflammatory reaction was
      detected in the lungs of the laminin-treated groups. In addition, laminin
      treatment of Pb265 resulted in a less severe infection as revealed by the lower
      fungal loads recovered from lungs. Antibody and cytokine levels, however, did not
      change after laminin treatment. Altogether, our results demonstrate that laminin
      binding to yeast cells diminishes P. brasiliensis pathogenicity. The lower
      inflammatory response observed with the virulent isolate and the decreased
      pulmonary fungal burden with the low-virulence isolate indicate an inhibitory
      effect of laminin treatment on P. brasiliensis infectivity and interaction with
      pulmonary host cells or extracellular matrix proteins.

PMID- 15158190
TI  - Complete development of Cryptosporidium parvum in rabbit chondrocytes (VELI
      cells).
AB  - Cryptosporidium parvum is an intracellular protozoan parasite that causes severe
      infection in humans and animals. The great difficulties in treating people and
      animals suffering from cryptosporidiosis have prompted the development of in
      vitro experimental models. The aim of this study was to demonstrate that C.
      parvum can complete its entire life cycle-from sporozoite to infective oocyst-in
      VELI cells (a line derived from primary culture of rabbit auricular
      chondrocytes). Successful infections were produced by inoculating cell cultures.
      Infection of MDCK, HTC-8 and VELI cells with C. parvum closely paralleled in vivo
      infections with regard to host cell location and chronology of parasite
      development. Oocysts which were produced in VELI cells were infective for infant
      NMRI mice. The growth of C. parvum in VELI cells provides a model, both simple
      and inexpensive, for testing anticryptosporidial drugs and studying host-parasite
      interactions.

PMID- 15158189
TI  - The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the
      parasite strain.
AB  - Previous studies provided evidence that the role of TNF in the control of
      Leishmania (Leishmania) major might vary with the parasite strain. Here, we
      analyzed the development and outcome of cutaneous leishmaniasis in C57BL/6 wild
      type (B6.WT) and TNF-deficient (B6. TNF(-/-)) mice infected with two different
      isolates of L. (L.) major (FRIEDLIN vs. BNI). L. (L.) major BNI caused
      progressive, fatal disease in B6.TNF(-/-) mice. In contrast, B6.TNF(-/-) mice
      infected with the L. (L.) major FRIEDLIN strain exhibited partial resistance
      characterized by chronic, non-healing skin lesions without lethality. Analysis of
      the tissue parasite numbers showed that the numbers of L. (L.) major FRIEDLIN and
      BNI parasites were comparable in footpads and lymph nodes of B6.TNF(-/-) mice,
      whereas in the spleen the parasite numbers were strikingly lower in the case of
      L. (L.) major FRIEDLIN. In vitro, cytokine-activated inflammatory macrophages
      killed L. (L.) major FRIEDLIN more efficiently than L. (L.) major BNI. These
      results suggest that in the absence of TNF, the course of leishmaniasis depends
      on the biology of the inoculated L. (L.) major strain, which most likely explains
      the previously published discrepant results on the role of TNF in leishmaniasis.

PMID- 15158192
TI  - Influenza A viruses possessing type B hemagglutinin and neuraminidase: potential
      as vaccine components.
AB  - A licensed live attenuated influenza vaccine is available as a trivalent mixture
      of types A (H1N1 and H3N2) and B vaccine viruses. Thus, interference among these
      viruses could restrict their replication, affecting vaccine efficacy. One
      approach to overcoming this potential problem is to use a chimeric virus
      possessing type B hemagglutinin (HA) and neuraminidase (NA) in a type A vaccine
      virus background. We previously generated a type A virus possessing a chimeric HA
      in which the entire ectodomain of the type A HA molecule was replaced with that
      of the type B HA, and showed that this virus protected mice from challenge by a
      wild-type B virus. In the study described here, we generated type A/B chimeric
      viruses carrying not only the chimeric (A/B) HA, but also the full-length type B
      NA instead of the type A NA, resulting in (A/B) HA/NA chimeric viruses possessing
      type B HA and NA ectodomains in the background of a type A virus. These (A/B)
      HA/NA chimeric viruses were attenuated in both cell culture and mice as compared
      with the wild-type A virus. Our findings may allow an effective live influenza
      vaccine to be produced from a single master strain, providing a model for the
      design of future live influenza vaccines.

PMID- 15158191
TI  - Risk factors for severe malaria in Bamako, Mali: a matched case-control study.
AB  - The aim of this case-control study was to identify epidemiological risk factors
      for severe malaria among children living in Bamako, a malaria-endemic area. For
      this, 260 healthy community controls were matched to 130 patients with severe
      malaria. Conditional multiple logistic regression analysis indicated that all
      examined independent factors associated with severe malaria are directly related
      to characteristics of the child's mother, with the exception of the child's own
      yellow fever vaccination history (odds ratio (OR): 1.93, 95% confidence intervals
      (CI(95%)) [1.10-3.37]). The following characteristics were all associated with a
      decreased risk of severe malaria in the child: maternal education (OR: 0.52,
      CI(95%) [0.31-0.86]), the mother's adequate knowledge about malaria (OR: 0.46,
      95% CI(95%) [0.25-0.86]), her use of mosquito bed nets (OR: 0.53, CI(95%) [0.30
      0.92]) and breast-feeding for at least 2 years (OR: 0.57, CI(95%) [0.33-0.94]).
      Conversely, chronic maternal disease (OR: ?3.16, CI(95%) [1.31-7.61]) was
      associated with an increased risk of severe malaria. These findings strongly
      support the hypothesis that maternal factors are central to the development of
      severe malaria in children. Programmes aiming to improve both maternal health and
      maternal education may reduce the incidence of severe malaria in children and
      should therefore be advocated in Bamako and in areas with similar epidemiological
      patterns for malaria.

PMID- 15158193
TI  - Ex vivo survival of peripheral blood mononuclear cells in sheep induced by bovine
      leukemia virus (BLV) mainly occurs in CD5- B cells that express BLV.
AB  - Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis
      (EBL). In a previous report, we found that in a sheep model, only CD5(-) B cells
      proliferated clonally, while CD5(+) B cells rapidly decreased when the disease
      progressed to the lymphoma stage. We demonstrate here that, although both CD5(+)
      and CD5(-) B cells, but not CD4(+) T, CD8(+) T and gammadeltaTCR(+)T cells, are
      protected from spontaneous ex vivo apoptosis in sheep infected with wild-type and
      a mutant BLV that encodes a mutant Tax D247G protein with elevated trans
      activation activity, only CD5(-) B cells become the main target for ex vivo
      survival when the disease proceeds to the persistent lymphocytotic stage, which
      showed an increased expansion of the CD5(-) B cells. In addition, we identified,
      by four-color flow cytometric analysis, that in CD5(-) B cells, the apoptotic
      rates of cells that expressed wild-type and mutant BLV were greatly decreased
      compared with those of BLV-negative cells. There was only a slight reduction in
      the apoptotic rates in BLV-positive cells from CD5(+) B cells. In addition,
      supernatants from peripheral blood mononuclear cell (PBMC) cultures from wild
      type- and mutant BLV-infected sheep mainly protected CD5(-) B cells from
      spontaneous apoptosis. Our results suggest that, although BLV can protect both
      CD5(+) and CD5(-) B cells from ex vivo apoptosis, the mechanisms accounting for
      the ex vivo survival between these two B-cell subsets differ. Therefore, it
      appears that the phenotypic changes in cells that express CD5 at the lymphoma
      stage could result from a difference in susceptibility to apoptosis in CD5(+) and
      CD5(-) B cells in BLV-infected sheep.

PMID- 15158194
TI  - Regional distribution of two related Northeast Asian genotypes of JC virus, CY-a
      and -b: implications for the dispersal of Northeast Asians.
AB  - JC virus (JCV) is a useful marker to trace human dispersal. Two genotypes of JCV
      (MY and CY) are mainly distributed in Northeast Asia. The population history of
      people carrying MY has been studied in some detail but that of people carrying CY
      remains poorly understood. To gain insights into the population history of
      Northeast Asians carrying CY we analyzed the genetic variation in CY isolates. We
      constructed a neighbor-joining phylogenetic tree from 28 complete CY DNA
      sequences: on the resultant tree the CY DNA sequences diverged into two clades,
      designated CY-a and -b, each clustered with a high bootstrap probability. The
      split into CY-a and -b was estimated to have occurred about 10 000 years ago,
      based on K(s) values (synonymous substitutions per synonymous site) and the
      suggested rate of synonymous nucleotide substitutions. Comparison of the 28
      complete CY sequences revealed six nucleotide mismatches between CY-a and -b, one
      of which showed a restriction fragment length polymorphism (RFLP). We then PCR
      amplified a region of the genome containing this polymorphic site from many CY
      isolates in various Northeast Asian populations and classified the isolates into
      CY-a or -b according to the RFLP analysis. CY-a was more abundant than CY-b in
      various Chinese and Japanese populations but CY-b was more abundant than CY-a in
      South Koreans. On the basis of the present findings we inferred the population
      history in East Asians carrying CY.

PMID- 15158195
TI  - Identification of enolase as a laminin-binding protein on the surface of
      Staphylococcus aureus.
AB  - We have previously demonstrated that Staphylococcus aureus, a highly invasive
      bacteria, presents a 52-kDa surface protein that mediates its binding to laminin.
      In order to better characterize this receptor, we excised this putative laminin
      receptor from two-dimensional (2-D) PAGE and used it as antigen for raising a
      mouse hyperimmune serum which was for screening an S. aureus expression library.
      A single clone of 0.3 kb was obtained, and its sequence revealed 100% homology
      with S. aureus alpha-enolase. Moreover, amino acid sequencing of the 52-kDa
      protein eluted from the 2-D gel indicated its molecular homology with alpha
      enolase, an enzyme that presents a high evolutionary conservation among species.
      In parallel, monoclonal antibodies raised against the S. aureus 52-kDa band also
      recognized yeast alpha-enolase in western blot analysis. These monoclonal
      antibodies were also able to promote capture of iodine-labeled bacteria when
      adsorbed to a solid phase, and this capture was inhibited by the addition of
      excess rabbit muscle alpha-enolase. Finally, the cell surface localization of S.
      aureus alpha-enolase was further confirmed by flow cytometry. Hence, alpha
      enolase might play a critical role in the pathogenesis of S. aureus by allowing
      its adherence to laminin-containing extracellular matrix.

PMID- 15158196
TI  - Innate immune recognition of microbes through Nod1 and Nod2: implications for
      disease.
AB  - Nod1 and Nod2 are cytosolic proteins involved in intracellular recognition of
      microbes and their products. Recently, it was shown that these proteins recognize
      different moieties of bacterial peptidoglycan (PGN) mediating non-specific
      pathogen resistance and possibly generating signals for the adaptive immune
      response. Moreover, mutations in the gene encoding Nod2 are associated with
      increased susceptibility to chronic inflammatory disorders.

PMID- 15158198
TI  - Biofilm formation and dispersal in Xanthomonas campestris.
AB  - Xanthomonas campestris pathovar campestris is the causal agent of black rot
      disease of cruciferous plants. A cell-cell signalling system encoded by genes
      within the rpf cluster is required for the full virulence of this plant pathogen.
      This system has recently been implicated in regulation of the formation and
      dispersal of Xanthomonas biofilms.

PMID- 15158197
TI  - Syndecans and HIV-1 pathogenesis.
AB  - The exploitation of receptors represents a common microbial strategy to survive
      in the hostile environment of the host. A growing body of evidence suggests that
      HIV-1 exploits a specific class of receptors-the syndecans-to facilitate
      colonization of the host.

PMID- 15158199
TI  - What kind of message does IL-12/IL-23 bring to macrophages and dendritic cells?
AB  - The present review illustrates the current knowledge on the autocrine effect of
      IL-12, and the putative contribution of IL-23, on macrophages and dendritic
      cells, focusing on cell activation and microbicidal activity. Here, we present
      convincing evidence that IL-12 is not only a connective element between accessory
      cells and lymphocytes, but it is also a key molecule for programming the
      macrophage and dendritic cell functions.

PMID- 15158200
TI  - The mystery of guttural pouch mycosis: the paradox of advancing knowledge of a
      rare disease.

PMID- 15158201
TI  - The time is right for acute phase protein assays.

PMID- 15158202
TI  - Muscular dystrophies: expanding our knowledge in companion animals.

PMID- 15158203
TI  - Chlamydial infections of domestic ruminants and swine: new nomenclature and new
      knowledge.

PMID- 15158204
TI  - Keratinocytes and veterinary dermatology: a century of refined culture.

PMID- 15158206
TI  - Current research on acute phase proteins in veterinary diagnosis: an overview.
AB  - The acute phase proteins (APP) are a group of blood proteins that contribute to
      restoring homeostasis and limiting microbial growth in an antibody-independent
      manner in animals subjected to infection, inflammation, surgical trauma or
      stress. In the last two decades, many advances have been made in monitoring APP
      in both farm and companion animals for clinical and experimental purposes. Also,
      the mechanism of the APP response is receiving attention in veterinary science in
      connection with the innate immune systems of animals. This review describes the
      results of recent research on animal APP, with special reference to their
      induction and regulatory mechanisms, their biological functions, and their
      current and future applications to veterinary diagnosis and animal production.

PMID- 15158205
TI  - An epidemiological approach to prevention and control of three common heritable
      diseases in canine pedigree breeds in the United Kingdom.
AB  - This paper reviews recent epidemiological research in the United Kingdom for
      controlling deafness in Dalmatians, glaucoma in flat coated retrievers and great
      Danes and hip dysplasia in flat coated retrievers, Newfoundlands, Gordon setters
      and Labrador retrievers. These studies assessed the prevalence of the disease,
      identified the factors affecting prevalence, and developed predictive statistical
      models of offspring/parent relationships. For each disease/breed combination, the
      research identified those sires and dams that might justifiably be regarded as
      suitable/unsuitable as potential parents in a selective breeding strategy to
      control or prevent the disease. Future progress in the control of these diseases
      is likely to come from greater understanding of their mode of inheritance.
      Insight, even for these complex diseases, can be derived from further detailed
      statistical evaluation of datasets such as those described in this paper.

PMID- 15158207
TI  - Postweaning multisystemic wasting syndrome: a review of aetiology, diagnosis and
      pathology.
AB  - This review paper concentrates on the aetiology, diagnosis, and pathological
      aspects of postweaning multisystemic wasting syndrome (PMWS). PMWS was first
      recognized in Canada in 1996 as a new emerging disease which caused wasting in
      postweaned pigs. Since then, PMWS has been recognized in pigs in many countries.
      The syndrome is caused by a DNA virus referred to as porcine circovirus 2 (PCV2),
      which is classified in the family Circoviridae. PMWS primarily occurs in pigs
      between 25 and 120 days of age with the highest number of cases occurring between
      60 and 80 days of age. The diagnosis of PMWS must meet three criteria: (i) the
      presence of compatible clinical signs, (ii) the presence of characteristic
      microscopic lesions, and (iii) the presence of PCV2 within these lesions. In
      order to establish the diagnosis, techniques are required that link virus and
      tissue lesions, such as immunohistochemistry and in situ hybridization, but not
      polymerase chain reaction or virus isolation. The three criteria considered
      separately are not diagnostic of PMWS. For example, the detection of PCV2 alone
      does not indicate PMWS but merely PCV2 infection. A hallmark of microscopic
      lesions of PMWS is granulomatous inflammation in the lymph nodes, liver, spleen,
      tonsil, thymus, and Peyer's patches. Large, multiple, basophilic or amphophilic
      grape-like intracytoplasmic inclusion bodies are often seen in the cytoplasm of
      macrophages and multinucleated giant cells.

PMID- 15158208
TI  - The activity of the feline thyroglobulin promoter is compromised by flanking
      adenoviral sequence.
AB  - The use of human adenovirus (Ad) vectors for transcriptionally targeted thyroid
      gene therapy was investigated, aiming to develop a novel therapy for feline
      hyperthyroidism. Ad5 (El, E3 deleted) vectors were constructed in which the
      feline thyroglobulin promoter controls expression of the reporter gene
      chloramphenicol acetyl transferase (CAT). In FRTL-5 cells, CAT expression from
      adenoviral constructs harbouring the expression cassette was much reduced
      compared to controls transfected with the same cassette in a plasmid backbone,
      despite higher transduction efficiencies when viral vectors were used.
      Transfections with the "shuttle" plasmids utilised to create the adenoviral
      vectors also resulted in reduced expression compared to controls. In both viruses
      and shuttle plasmids, consistently lower expression was noted when the cassette
      was in the left to right orientation than the right to left. These results
      suggest cis acting elements in the flanking adenoviral sequences may compromise
      the activity of the feline thyroglobulin promoter and thus make Ad5 an unsuitable
      vector for transcriptionally targeted gene therapy in feline hyperthyroidism.

PMID- 15158209
TI  - The mystery of fungal infection in the guttural pouches.
AB  - Advances in the understanding of guttural pouch physiology and novel therapeutic
      approaches to mycotic infections in the horse are reviewed. It is suggested that
      the guttural pouches may contribute to the regulation of arterial blood
      temperature, cooling the circulation to the brain to below body temperature.
      Aspergillus spp. is the major organism found in a guttural pouch affected with
      mycosis but it is unclear why this agent becomes aggressive. Conventional therapy
      aims to prevent fatal haemorrhage and to treat any neurological lesions but it is
      desirable to try to prevent the disease. A technique consisting of inserting a
      transarterial coil into the internal carotid, external carotid and maxillary
      arteries in normal and affected horses has been reported to be rapid, safe and
      effective in occluding the arteries and in inducing regression of the mycotic
      lesions without adjunctive medical treatment. When faced with acute and
      uncontrollable epistaxis in the field, the most effective means to reduce
      haemorrhage is probably the occlusion of both common carotid arteries. However,
      how such arterial occlusions can result in the successful management of guttural
      pouch mycosis without antifungal medication remains a mystery.

PMID- 15158210
TI  - Metabolic parameters and blood leukocyte profiles in cows from herds with high or
      low mastitis incidence.
AB  - The objective of this study was to determine whether there were differences in
      metabolic parameters and blood leukocyte profiles between cows in herds with high
      or low yearly mastitis incidence. In this study, 271 cows from 20 high yielding
      dairy herds were examined. According to the selection criteria, all herds had low
      somatic cell counts. Ten of the selected herds represented low mastitis treatment
      incidence (LMI) and ten herds had high mastitis treatment incidence (HMI). The
      farms were visited once and blood samples were taken from each cow that was in
      the interval from three weeks before to 15 weeks after parturition. The
      eosinophil count was significantly lower among cows from the HMI herds in the
      period from four weeks to 15 weeks after parturition. The plasma concentrations
      of beta-hydroxybutyrate, glucose, insulin and urea did not differ between groups,
      but the concentration of nonesterified fatty acids was significantly higher among
      HMI cows during the period three weeks after parturition. The concentration of
      the amino acid tryptophan in plasma was significantly lower among the HMI cows
      prior to parturition. Glutamine was significantly lower in cows from HMI herds
      during the first three weeks after parturition. Arginine was consistently lower
      in HMI cows, although the decrease was only significant during the period from
      four to fifteen weeks after parturition. The results suggest that there were
      differences in the metabolism and immune status between herds with high or low
      yearly mastitis treatment incidence indicating an increased metabolic stress in
      HMI cows.

PMID- 15158211
TI  - Growth characteristics of porcine chlamydial strains in different cell culture
      systems and comparison with ovine and avian chlamydial strains.
AB  - Porcine Chlamydiaceae were cultivated under various culture conditions and we
      compared their growth characteristics with those of ruminant and avian strains.
      The combination of centrifugation assisted cell culture infection and
      cycloheximide treatment of Vero cell coverslip cultures provided the highest
      inclusion numbers with all chlamydial strains. Interestingly, the use of Iscove's
      modified Dulbecco's medium instead of Eagle's minimal essential medium
      significantly increased Chlamydia suis inclusion counts. C. suis and
      Chlamydophila pecorum inclusion numbers were markedly increased in CaCo cells,
      compared with Vero cells. This accelerated growth of porcine Chlamydiaceae under
      certain cultivation conditions may be helpful for the propagation of low
      chlamydial numbers or for their isolation from field samples. The intracellular
      distribution of porcine Chlamydiaceae in polarised CaCo cells clearly
      demonstrated differences between the chlamydial strains: C. pecorum 1710S
      inclusions were predominantly localised in the apical cytoplasm, C. suis S45
      inclusions, however, were mostly situated in lower cytoplasmatic compartments.
      These findings might reflect biological differences in vivo.

PMID- 15158212
TI  - A high yield method for growing primary canine keratinocytes.
AB  - From a small amount of starting material, a large quantity of canine
      keratinocytes can be generated for experimental purposes using a refined method
      of explant culture to initiate the growth of basal cells with a high
      proliferative potential. The dividing capacity of cultures was promoted by a
      system selecting clonogenic cells onto an i3T3 feeder layer in combination with
      carefully monitoring cell morphology and passaging to select out excessive
      numbers of differentiated keratinocytes. Levels of contaminating dermal
      fibroblasts, which if left unchecked will overgrow keratinocytes, were kept to a
      minimum by a combination of careful explant micro-dissection to remove dermis,
      eliminating explants with signs of fibroblast growth as well as using cholera
      toxin, EGF and i3T3 feeder layers. The advantage of the method described is that
      it does not rely on the provision of large quantities of starting material
      thereby reducing the need for repeated tissue sampling, and passage numbers of
      five or six can be routinely achieved. This technique can therefore be useful to
      experimenters who require a regular and reliable source of cells for their
      studies.

PMID- 15158213
TI  - Electrodiagnostic evaluation in feline hypertrophic muscular dystrophy.
AB  - Standard needle electromyography (EMG) of 56 muscles and nerve conduction
      velocities (NCV) of the ulnar and common peroneal nerves were investigated in
      each of six cats affected with hypertrophic feline muscular dystrophy, 10 related
      heterozygote carriers and 10 normal cats. The EMG findings were considered normal
      in carrier and control cats, and consisted of 33% normal readings, 22% myotonic
      discharges, 18% fibrillation potentials, 11% prolonged insertional potentials,
      10% complex repetitive discharges and 6% positive sharp waves in affected cats.
      Muscles of the proximal limbs were most frequently affected. No differences in
      NCV were found between the three cat groups. It was concluded that dystrophin
      deficient dystrophic cats have widespread and frequent EMG changes, predominantly
      myotonic discharges and fibrillation potentials, which are most pronounced in the
      proximal appendicular muscles.

PMID- 15158214
TI  - Re-emergence of foot-and-mouth disease in Botswana.
AB  - The re-emergence of foot-and-mouth disease (FMD) in Botswana is reported. The
      disease outbreak occurred in the Matsiloje Extension Area of Francistown
      veterinary district situated in the northeastern part of the country in an Office
      International des epizooties (OIE) recognized FMD free zone without vaccination.
      The disease affected cattle only and did not spillover into sheep and goats
      resident in the same extension area, as demonstrated by lack of seroconversion to
      FMD when tested. The virus isolate associated with the outbreak was identified as
      FMD virus; Southern African Territories (SAT) type SAT-2. The disease outbreak is
      discussed in relation to FMD outbreaks that have occurred previously within and
      outside Botswana.

PMID- 15158215
TI  - Conservation of the uvrC gene sequence in Mycoplasma bovis and its use in routine
      PCR diagnosis.

PMID- 15158216
TI  - Ultrasonographic localisation of thrombi in the caudal vena cava and hepatic
      veins in a heifer.

PMID- 15158217
TI  - High field body MR imaging: preliminary experiences.
AB  - Whole-body magnetic resonance (MR) scanners at high field strengths (> or =3 T)
      have been introduced in expectation of a larger signal-to-noise ratio (SNR),
      which would decrease the length of scan time or improve the spatial resolution.
      In this paper, the advantages and disadvantages of the high field MR imaging are
      discussed. Although the building of the radio frequency (RF) coil, safety and the
      specific absorption rate (SAR) are issues, the application of high field MR
      imaging is promising. The optimization of all parameters including injection rate
      of Gd-DTPA is necessary for high field MR imaging to obtain maximal results;
      however, we hope that high field MR imaging can be used in routine clinical
      applications in the future.

PMID- 15158218
TI  - Left hemisphere and male sex dominance of cerebral hemiatrophy (Dyke-Davidoff
      Masson Syndrome).
AB  - Although radiological findings of cerebral hemiatrophy (Dyke-Davidoff-Masson
      Syndrome) are well known, there is no systematic study about the gender and the
      affected side in this syndrome. Brain images in 26 patients (mean aged 11) with
      cerebral hemiatrophy were retrospectively reviewed. Nineteen patients (73.5%)
      were male and seven patients (26.5%) were female. Left hemisphere involvement was
      seen in 18 patients (69.2%) and right hemisphere involvement was seen in eight
      patients (30.8%). We conclude that male gender and left side involvement are
      frequent in cerebral hemiatrophy disease.

PMID- 15158219
TI  - Neurosarcoidosis: findings in MRI.
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown etiology.
      Neurologic manifestations occur usually as a part of the spectrum of the systemic
      disease. The aim of this retrospective study was to evaluate the role of magnetic
      resonance imaging (MRI) in the diagnosis of patients with neurosarcoidosis (NS).
      Seven patients with sarcoidosis could be included into the study. All patients
      had neurological symptoms and were evaluated with MRI revealing a wide spectrum
      of findings: periventricular and white matter lesions, multiple or solitary supra
      and infratentorial brain lesions, leptomeningeal enhancement, involvement of
      brain nerves and intramedullar lesions. These findings are not specific for
      sarcoidosis and must be considered with the clinical course of the patient in
      arriving at the correct diagnosis.

PMID- 15158220
TI  - Intradural disc herniation with cranial migration of an excluded fragment.
AB  - Intradural herniation is a rare complication of the intervertebral disc disease.
      The history and present clinical findings may suggest the diagnosis. Although the
      myelographic signs are well known, intradural hernias have seldom been
      illustrated by magnetic resonance imaging (MRI). We present the case of an
      intradural disc hernia with cranial migration of a sequestrated fragment
      illustrated by both myelography and MRI. To our knowledge, such a case has never
      been reported in the literature so far.

PMID- 15158221
TI  - Sickle cell cerebrovascular disease: usual and unusual findings on MR imaging and
      MR angiography.
AB  - This paper demonstrates usual and unusual findings on MR imaging (MRI) including
      fluid-attenuated inversion recovery (FLAIR), diffusion- and perfusion-weighted
      image and MR angiography (MRA) in 30 patients with sickle cell cerebrovascular
      disease. This paper also illustrates the underlying pathophysiology of sickle
      cell cerebrovascular disease by using the cases with usual and unusual MR
      findings, including long-time follow-up cases during transfusion therapy. MRI and
      MRA are useful in defining the basis for stroke and assessing the effects of
      chronic transfusion therapy.

PMID- 15158222
TI  - Chordoma mimicking the trigeminal schwannoma: a case report.
AB  - Intracranial chordomas are rare tumor arising from the remnants of embryologic
      notochord. Bony destruction and tumor calcification are their characters. Now we
      represent an extra-axial tumor with an unusual dumbbell shape in the right
      Meckel's cave and the appearance mimics the trigeminal schwannomas. However, the
      histopathological findings reveal a chordoma. Bony destruction in the right
      petrous bone and clivus provides a hint to make appropriate diagnosis.

PMID- 15158223
TI  - Pulmonary cryptococcosis in immunocompetent patients: HRCT characteristics.
AB  - We analyzed the high-resolution CT (HRCT) findings of cryptococcosis in
      immunocompetent patients. The predominant manifestations were multiple nodules
      (n=6) and a single nodule (n=7). Regarding the pattern of multiple nodules, two
      cases of cavities or necrosis, four cases of surrounding centrilobular
      micronodules and five cases of "acinar" nodules were seen. No "tree-in-bud"
      appearance was detected. Five of seven cases of a single nodule were classified
      as polygonal, and two of them were round. Two cases accompanied micronodules and
      one case cavitation. Although no "tree-in-bud" appearance was observed, pulmonary
      cryptococcosis mimics tuberculosis.

PMID- 15158224
TI  - Radiologic aspects of abdominal hydatidosis in children: a study of 31 cases in
      Turkey.
AB  - OBJECTIVE: To determine the location and radiological characteristics in children
      with abdominal hydatid disease (HD). MATERIALS AND METHODS: Thirty-one children
      (average age: 7.2 years) with abdominal HD were studied. The number, location,
      diameter and internal architecture of the cysts were assessed with abdominal
      ultrasonography (US) and computed tomography (CT). Density measurements and
      enhancement patterns were determined on CT. RESULTS: Twenty-one children had
      hepatic HD. The remaining 10 children had both hepatic and extrahepatic cysts.
      There were splenic cysts in five children, peritoneal cysts in two children and
      combined splenic and peritoneal cysts in three children. The most common site of
      the cysts was the liver (64%), followed by the spleen (20%) and the peritoneal
      cavity (16%). The seven intraabdominal cysts, which were not detected by US, were
      20 mm or less in diameter. CONCLUSION: CT may demonstrate additional small
      intrahepatic or unsuspected extrahepatic cysts. Although rare, splenic or
      peritoneal hydatidosis should be included in the differential diagnosis of a
      cystic splenic or peritoneal lesion. Familiarity with atypical locations of HD
      may be helpful in making a prompt, accurate diagnosis. We think that in
      particular patients, especially those who had diagnostic problem and who are
      under surgical planning, CT should be performed additionally.

PMID- 15158225
TI  - CT features of bladder small cell carcinoma.
AB  - Computed tomography (CT) features of six patients with pathologically proven
      bladder small cell carcinoma (SCC) were analyzed retrospectively. CT revealed
      these tumors as large, enhancing, broad-based polypoid intramural masses with or
      without cystic portions, extending to the perivesical area. Tumor calcification
      was found in one patient, and lymphadenopathy in four patients. The staging at
      the time of diagnosis was C in three patients, and D1 in another three patients.
      Follow-up CT showed brain metastasis in one patient, and liver metastasis in two
      patients.

PMID- 15158226
TI  - Chondrolipoma in the palm of a child: sonographic and MR findings.
AB  - Chondrolipoma is a rare form of benign mesenchymoma. We report the case of a
      chondrolipoma in the palm of a 9-year-old boy with corresponding sonographic,
      magnetic resonance (MR) and pathological findings.

PMID- 15158227
TI  - Lymphomatoid granulomatosis in a pediatric patient.
AB  - We report the radiology and pathology of a pediatric patient with lymphomatoid
      granulomatosis (LG) and review the literature, with an emphasis on the
      radiological findings and on the small subset of pediatric patients with this
      rare condition.

PMID- 15158228
TI  - Melorheostosis with scleroderma.
AB  - The association of linear scleroderma with melorheostosis is very rare. Until
      now, only a few cases have been reported in the English literature. We describe a
      case of melorheostosis of a rib associated with overlying skin changes.

PMID- 15158229
TI  - Radiologic demonstration of temporal development of bizarre parosteal
      osteochondromatous proliferation.
AB  - We report a case of bizarre parosteal osteochondromatous proliferation (BPOP) in
      which radiologic examinations showed temporal development of BPOP following a
      traumatic event. This evidence supports the theory that BPOP is caused by trauma.

PMID- 15158230
TI  - Spinous process fractures associated with Baastrup disease.
AB  - Patients with Baastrup disease may experience pain owing to irritation of the
      periosteum or adventitial bursae between abutting spinous processes. We are not
      aware of any reports in the literature that describe stress fractures of the
      spinous fractures in patients with Baastrup disease. In this case report, we
      present two cases of spinous process fractures in lumbar vertebrae associated
      with Baastrup disease and describe their appearance with conventional
      radiography, bone scintigraphy, computed tomography (CT) and magnetic resonance
      (MR) imaging.

PMID- 15158231
TI  - Percutaneous retrieval of 20 centrally dislodged Port-A catheter fragments.
AB  - A total of 20 patients with centrally embolized Port-A catheter fragments
      underwent the percutaneous retrieval procedures at our hospital. The causes of
      the dislodgement of these catheters included bad connection between the port and
      catheter, angulation or distortion at the anastomosis site, severing the catheter
      during insertion and removal of the catheter, improper catheter position and
      fatigue of the catheter. Consequently, improper procedure handling by the
      inexperienced surgeons could be considered as the most frequent cause of
      embolization. The percutaneous retrieval procedures were successful in all
      centrally embolized fragments. Of 20 successful retrievals, 16 were performed
      will loop snare catheters and 4 with Dormia basket retrievers.

PMID- 15158234
TI  - [Autologous blood predeposit: do we throw out the baby with the bath water?].

PMID- 15158235
TI  - [Myasthenia gravis, pregnancy and delivery: a series of ten cases].
AB  - OBJECTIVE: To study the reciprocal interferences between pregnancy and myasthenia
      gravis (MG) and to describe obstetric and anaesthetic management during labour
      and the post-partum period. STUDY DESIGN: Retrospective, single centre study.
      METHODS: The files of 10 patients with MG, who delivered between October 1994 and
      May 2002, were examined. RESULTS: No stillbirth occurred and all pregnancies were
      brought to term. All patients were maintained on their long-term
      anticholinesterase medications during pregnancy. Seven exacerbations were
      detected and controlled, five by increasing the anticholinesterase treatment, one
      by using plasmapheresis and one by using intravenous immunoglobulins. No patient
      required admission to the intensive care unit during pregnancy. All patients had
      a pre-anaesthetic visit at/near 33 weeks of gestation. Delivery was induced for
      six patients. Regional analgesia was performed early in labour (epidural, n = 7;
      combined spinal-epidural = 2) using low concentrations of local anaesthetic and
      no complication was detected. Three patients required a caesarean section for an
      obstetrical indication. Seven patients delivered vaginally using instrumental
      extraction (n = 5). During the post-partum period, four patients were monitored
      in the intensive care unit during 48 h and close neurological follow-up disclosed
      no exacerbation during the first 6 post-partum weeks. CONCLUSIONS: MG has no
      significant effect on the course of pregnancy and delivery, but MG exacerbation
      can occur, especially in the first trimester. Regional analgesia is medically
      indicated and must be performed early in labour, using low concentration of local
      anaesthetic to lessen the risk of motor block.

PMID- 15158236
TI  - [Impact of the law of the 4 March 2002 relative to patients' rights on request
      for medical information received in a medical dispatching center and mobile
      intensive care unit (Samu 93)].
AB  - INTRODUCTION: Law of the 4 March 2002 allowed patient's access to his medical
      record. This law could increase the number of requests in medical dispatching
      centers and prehospital intensive care units. OBJECTIVE: The aim of this study
      was to evaluate the impact of this law on the number of requests for medical
      information received in our unit. METHODS: Since the promulgation of the law,
      from March to December 2002, medical requests were prospectively collected and
      classified in categories including request for transmission of medical record.
      Requests received before the law, from January 2000 to February 2002 were
      classified according to the same items. Number of requests received during the
      two periods were compared according to the total number of medical record managed
      in our medical dispatching center and prehospital intensive care unit. RESULTS:
      The total number of requests for medical information significantly increased
      since the law of March 2002 (results are expressed as cases per month per 10 000
      record: 4.8 +/- 2.5 vs. 8.0 +/- 4.5; p = 0.04). Specific request for
      transmissions of medical record significantly increased since the law (1.3 +/-
      1.6 vs. 3.0 +/- 3.0; P = 0.046). This increase was progressive and constant since
      March 2002. DISCUSSION: Physicians and patients should take in consideration
      consequences of this law. Physician should be vigilant with the quality of their
      medical dossiers. Interpretation of this law and its ethics consequences will
      probably be discussed again as one should not exclude perverse impact of this
      law. In effect, insurances and mutual insurances companies could find in this law
      a way to obtain medical information, such as circumstances of death, previously
      unavailable. CONCLUSION: The law of 4 March 2002 relative to patients' rights
      significantly increased number of requests for medical information received in
      our dispatching center and prehospital intensive care unit.

PMID- 15158237
TI  - [Do we need autologous blood donation?].
AB  - The aim of preoperative autologous blood donation (ABD) was to reduce both the
      risk of transfusion transmitted disease and the need of blood from donors. Since
      ABD has been developed, the conditions of surgery and the criteria of choice have
      been modified thus leading to actualise the evaluation of this therapy. The first
      theoretical advantage of ABD is prevention of transfusion-transmitted disease
      namely viral infections such as HIV or hepatitis virus or emerging virus.
      Actually, the very low residual risk that remains from allogeneic transfusion
      after appropriate selection of donors, leukoreduction and nuclear acid testing
      does not argue for ABD. On the other hand, the risk of bacterial contamination
      must be taken in account for both ABD and homologous transfusion. A meta-analysis
      showed that ABD reduces the exposure to homologous transfusion (OR: 0.17).
      Clinical studies showed that patients who predonated autologous blood were more
      likely to receive any blood transfusions (autologous and/or allogeneic) than
      those who did not (OR: 3.31). More, the reduction of exposure to allogeneic
      transfusion may be questioned in view of prescription bias. Additionally, ABD is
      poorly cost-effective. It leads to significant blood wastage as in most of the
      studies about half of the units are discarded. In conclusion the interest of ABD
      has not been sufficiently evaluated. The interest of this therapy remains to be
      demonstrated.

PMID- 15158238
TI  - [Changes in blood gases with temperature: implications for clinical practice].
AB  - OBJECTIVE: To understand changes in blood gases results with core temperature.
      METHODS: Analysis from two case reports. RESULTS: Hypothermia induces a decrease
      in PaCO(2) with a related increase in pH, thus a physiologic alkalosis. Decrease
      in PaCO(2) is due to an increase of gas solubility and a decrease of peripheral
      consumption that can be estimated from comparison between corrected and non
      corrected for temperature blood gases. For O(2), variations of temperature induce
      variations of solubility but also of haemoglobin affinity for O(2). During
      hyperthermia, haemoglobin affinity for O(2) is decreased with a decreased SvO(2)
      for a same PvO(2). SvO(2) ischemic or therapeutic thresholds are thus modified
      with core temperature. CONCLUSION: Blood gases cannot be understood without
      patient core temperature. Physiologic variations of PaCO(2) and pH must probably
      be tolerated. Ischemic threshold should be estimated on PvO(2), not only on
      PvO(2).

PMID- 15158239
TI  - [Postnatal maturation of the diaphragm muscle: ultrastructural and functional
      aspects].
AB  - OBJECTIVE: In the diaphragm muscle, postnatal maturation is associated with major
      histological and biochemical modifications, as well as a progressive development
      of the sarcoplasmic reticulum (SR), which in turn are responsible for the
      progressive postnatal improvement in diaphragmatic contractility. However, the
      mechanisms by which postnatal maturation induces this improvement in
      diaphragmatic contractility remain poorly understood and controversial. The aim
      of this review is to analyze the data from the literature regarding the process
      involved in the postnatal improvement in diaphragmatic contractility. DATA
      SOURCES: References obtained from Pubmed((R)) databank using keywords (diaphragm
      muscle, postnatal maturation, contractility, muscular fatigue, cross-bridge).
      DATA SYNTHESIS: From a cytological point of view, the postnatal development of
      the diaphragm muscle is processed in two successive generations of fiber types,
      corresponding to the progressive adaptation of the diaphragm muscle to its
      physiological function. Indeed, the proportion in type I (slow, aerobic) and type
      IIB fibers (fast, anaerobic) progressively increases with postnatal maturation,
      while the proportion in type IIA fibers (fast, intermediate) progressively
      decreases. The histochemical classification of the type of fiber corresponds to
      the expression of the different isoforms of myosin heavy chains (MHC). Two types
      of MHC: MHC embryologic (MCH-emb) and MHC neonatal (MCH-neo), and one type of
      myosin light chains (MLC) are expressed in the foetal skeletal muscles, then are
      progressively eliminated during postnatal maturation. For many authors, this
      progressive transition from immature MHC (MCH-emb and neo) to adult MHC (by
      chronological order of appearance: MHC-2A, MHC-lente, MHC-2X, MHC-2B) could be
      responsible for the progressive improvement in postnatal diaphragmatic
      contractility. This transition could be modulated by external factors, mainly
      including neural and hormonal stimuli. For others, this transition in MHC
      expression do not play a major role, and other factors, including the postnatal
      maturation of the ryanodine receptor (RyR) or developmental changes in cross
      bridges (CB) properties should play a central role. The most recent hypotheses
      proposed included the possibility of a postnatal transition in the expression of
      structural proteins, which are playing a major role in the maintenance of the
      stability of the sarcomer, and therefore in force generation.

PMID- 15158240
TI  - [Surgery to save body-packers].
AB  - Cocaine body packing may expose to the risk of intestinal obstruction or acute
      cocaine poisoning. During the last five years (1998-2002), 17 symptomatic body
      packers were admitted to our intensive care unit, for a closed monitoring.
      Clinical evolution of three patients required a surgical intervention. The first
      patient had a laparotomy, in the presence of an occlusive syndrome, to recover
      the packets of cocaine. The second patient presented peritonitis, in relation to
      an ileal perforation, treated with an intestinal segment resection followed by a
      double ileostomy. The third patient presented severe ventricular dysrhythmia, due
      to cocaine toxicity, after a bullet disruption in the stomach. Adrenaline and
      labetalol-combined therapy as well as gastric incision to recover the bullets
      were needed to allow cardiovascular stabilization. In these three cases, the
      surgical treatment allowed patient survival.

PMID- 15158241
TI  - [Haemorrhagic colitis after colonoscopy].
AB  - We report the case of a 43-year-old woman with an acute haemorrhagic colitis
      after colonoscopy with ambulatory anaesthesia. The diagnosis is likely to have
      been glutaraldehyde induced colitis (used for disinfection of the endoscope). The
      patient recovered spontaneously completely.

PMID- 15158242
TI  - [Severe bone marrow necrosis associated with septic shock in the intensive care
      unit].
AB  - Unexplained cytopenias can be related to bone marrow necrosis (BMN) in critically
      ill patients as it can be encountered in several diseases or life-threatening
      conditions. We present the case of a 39-year-old woman with pancytopenia
      revealing a BMN in the setting of an acute pyelonephritis with septic shock,
      multiple organ failure and sickle cell trait. After a short review on the
      subject, we suggest that various haematological abnormalities occurring in
      critically ill patients may be related to a mild to severe marrow necrosis.

PMID- 15158243
TI  - [Spinal anaesthesia and Moya Moya disease].
AB  - Moya Moya is a rare disease of uncertain origin, characterised by stenosis of one
      or both of the internal carotid arteries and responsible of several neurological
      signs. We present the case of a boy with Moya Moya disease who was scheduled for
      an epiphisiodesis of the lateral malleola and had a spinal anaesthesia with
      hyperbaric bupivacaine 0.5% 10 mg without any perioperative complications. Any
      anaesthetic method could be used, provided special attention is given to avoid
      changes of capnea and blood pressure to preserve cerebral blood flow and palliate
      to cerebral flow steal.

PMID- 15158245
TI  - [Increase in bispectral index induced by antihyperalgesic dose of ketamine].
AB  - We report two cases of sudden increase in Bispectral Index (BIS) after the
      injection of low-dose ketamine for the prevention of postoperative hyperalgesia.
      The two patients were anaesthetised with a continuous infusion of remifentanil
      associated with propofol for one and isoflurane for the other. Changes in BIS
      occurred while the two patients were in a stable phase of surgery (beginning of
      parietal closure and suture of an anastomosis) and had a stable target
      concentration of anaesthetic agents. No others signs of awakening were observed.
      The BIS value returned progressively to 40-50 despite no increase in target
      concentration. None of the patients complained of intra-operative recall.

PMID- 15158244
TI  - [Sheehan's syndrome: an erratic diagnosis in the early postpartum].
AB  - Post-partum pituitary necrosis (Sheehan's syndrome) is a rare complication of the
      post-partum haemorrhage. The diagnosis can be erratic and often delayed. We
      report the case of a patient who had headaches and meningitis signs few hours
      after a post-partum haemorrhage. Magnetic Resonance Imaging (MRI) performed at
      day 2 showed a specific hypophysitis. The onset of asthenia, loss of weight,
      polyuro-polydipsy, persistent amenorrhoea and absence of lactation led to
      hormonal investigation. This permitted to diagnose global antehypopituitarism
      associated with diabetes insipidus. Progressive pituitary atrophy due to necrosis
      was found using MRI follow-up over 1 year. Our report summarises
      pathophysiological features of Sheehan's syndrome and early clinical and
      biological signs are discussed. MRI of the sellar region may be useful to early
      suspect the diagnosis.

PMID- 15158246
TI  - [Anaesthesia and amiodarone-associated hyperthyroidism].
AB  - Amiodarone can induce severe hyperthyroidism that justifies its withdrawal and
      initiation of antithyroid drugs. Impossibility to stop amiodarone, failure to
      control hyperthyroidism and unfavourable evolution can lead to thyroidectomy.
      Cardiac manifestations, persistence of hyperthyroidism and interactions between
      amiodarone and anaesthetic or haemodynamic drugs may contraindicate anaesthesia.
      We report nine consecutive cases of amiodarone-associated hyperthyroidism that
      prompted us to perform thyroidectomy under general anaesthesia. The features and
      anaesthetic data of patients were noted. The antithyroid medical treatment failed
      in all patients. After thyroidectomy, evolution was favourable in all nine cases,
      without any intra or postoperative complication, in spite of the extent of
      hyperthyroidism and the severity of the associated cardiac problems. Despite
      potential high risks, thyroidectomy for amiodarone-induced hyperthyroidism does
      not seem to increase morbidity or mortality and allows a quick return to
      euthyroidism and reintroduction of amiodarone.

PMID- 15158247
TI  - [When and how to start sedation in a neuro-intensive care patient?].
AB  - Sedatives drugs are part of the everyday care in the neuro-ICU. Reasons to sedate
      patients in neuro-ICU are as usual to ensure the comfort and to secure the
      patients, to permit nursing as well as to permit adaptation to the ventilator.
      But some objectives are specific in neuro-ICU as optimisation of cerebral
      haemodynamics and oxygenation, and to avoid a convulsive state or a dysautonomic
      syndrome. Starting the sedation usually necessitate a tracheal intubation and
      mechanical ventilation. Patients presenting with intracranial hypertension are at
      risk of developing cerebral ischaemia in case of cerebral haemodynamics
      alteration associated with anaesthetic drugs injection. Morphinomimetics increase
      intracranial pressure (ICP), but cerebral perfusion pressure and oxygenation
      (CPP) remain usually unaltered. Injection of an intravenous bolus of thiopental
      or propofol lowers ICP and CPP, but also the cerebral tissular oxygen
      consumption: the cerebral oxygenation seems therefore protected. The
      succinylcholine used for emergency tracheal intubation has no effect on the
      cerebral haemodynamic. Some more studies are needed to better understand the
      cerebral oxygenation at the local level when sedative drugs are injected or
      perfused in patients with intracranial hypertension.

PMID- 15158249
TI  - [Evaluation of the depth of sedation in neurocritical care: clinical scales,
      electrophysiological methods and BIS].
AB  - The primary goal of sedation is to achieve security and comfort of mechanically
      ventilated ICU patients. Delivery of pharmacologic agents must avoid over
      sedation, which increases morbidity by prolongation of the duration of mechanical
      ventilation. Similarly, under sedation may favour life-threatening events such as
      accidental extubation. Many clinical scales have been generated to regularly
      measure the level of sedation (consciousness and tolerance to the ICU
      environment). No electrophysiological monitor (BIS) has proved reliability for
      measuring the depth of sedation or analgesia yet. The presence of brain damage in
      ICU patients makes the level of sedation impossible to interpret. Glasgow coma
      scale, which is exclusively devoted to the consciousness domain, is the only
      recommendation that can be made in neurocritical care at the present time.

PMID- 15158248
TI  - [The agents used for sedation in neurointensive care unit].
AB  - Sedation and analgesia can be routinely prescribed in head injury patients. The
      goals of such sedation are three: brain protection, prevention and treatment of
      intracranial hypertension and therapeutic facilitation. In such situation, the
      use of sedative and analgesic therapy should respect the rate of cerebral blood
      flow/cerebral oxygen consumption coupling while preserving cerebral perfusion
      pressure and decreasing the intracranial pressure. This treatment should have an
      analgesic and myorelaxing action with short and predictable time of action. The
      ideal sedation agent with all these properties does not exist. Only the
      combination of several different pharmacological classes of compounds may reach
      this goal. Benzodiazepines are the most frequently used agents. In most of the
      cases they are associated with analgesic agents such as opioid or ketamine.
      Opioids may be the basic analgesic agents because they do not produce brain
      haemodynamic modifications if arterial pressure is maintained. Among them,
      sufentanil, thanks to its pharmacokinetics properties, remains the most
      prescribed opioid. However, in the future, remifentanil that presents a fast
      elimination may be more frequently used for neurological follow up of patients.
      Ketamine whose use is subject of debate, has the main advantage of maintaining
      haemodynamic status. Ketamine has no side effects on brain haemodynamic when used
      with propofol or midazolam. Taking into account their deleting effect on
      haemodynamic status and immune system, barbituric are no longer used as long term
      sedative agents. However, their use is still recommended in the cases of
      refractory intracranial hypertension. Propofol remains the ideal sedative agent
      because of its short duration action but its use is limited by its cost. Its use
      may be recommended for short time sedations with or without an opioid drug. The
      curare use should be restrain to refractory intracranial hypertension to usual
      treatments and happening during stimulation.

PMID- 15158251
TI  - [Complete ptosis following peribulbar anaesthesia for cataract surgery].

PMID- 15158250
TI  - [Sedation interruption in neurointensive care].
AB  - The reasons for sedation in neurointensive care can be divided into two main
      groups: (i) general indications, as for other intensive care patients, such as to
      allow the necessary treatments (therapeutic facilitation), controlling the states
      of agitations em leader; (ii) specific indications due to the neuro-physiologic
      effect of the sedatives: facilitation of the control of the intracranial pressure
      and lowering of the cortical excitability during the epileptic fits and thereby
      helping the recovery of the cerebral tissue and diminishing the secondary brain
      insults. It is important to remember that sedation is usually combined with the
      administration of opioids, which can potentiate the effect of the sedative drugs.
      The interruption of the sedation can be long- or short-termed. The definitive
      interruption is possible once the clinical and cerebral state of the patient does
      not justify any sedation, whereas the brief interruption allows a neurological
      reassessment. The amount of literature on sedation in intensive care is opposed
      to the few studies on neurointensive care: in January 2003, the American Society
      of Intensive Care has published recommendations for this topic without mentioning
      the interruption of sedation in neurointensive care patients. The aim of this
      article is to review the literature about the effects of the interruption of the
      sedation in neurointensive care patients.

PMID- 15158252
TI  - [Intussusception due to a lipoma: a rare cause of acute abdominal pain in adult].

PMID- 15158253
TI  - [Nosocomial transmission of hepatitis C from patient to patient in general
      anesthesia in the northern inter-region in 2001-2002].

PMID- 15158254
TI  - [Publication of questions and answers for teaching the second part of the second
      cycle of medical studies].

PMID- 15158255
TI  - Staphylococcal methicillin resistance: fine focus on folds and functions.
AB  - Globalisation has entailed a massive increase in trade and human mobility
      facilitating the rapid spread of infectious agents, including those that are drug
      resistant. A particularly serious threat to human health is posed by methicillin
      resistant staphylococcal strains which have acquired molecular mechanisms to
      evade the action of beta-lactam antibiotics (BLAs). Full expression of high-level
      methicillin resistance involves a complex network of molecules and depends
      primarily on sufficient expression of a penicillin-binding protein with low
      sensitivity towards BLAs. Other factors include the fine-tuned regulation of
      autolytic activity of cell-wall components, as well as an optimal rate of
      peptidoglycan precursor formation and a highly specific peptidoglycan precursor
      structure. Three-dimensional structural data are available on several of the
      pieces involved in the jigsaw puzzle and provide a molecular basis for the
      understanding of methicillin resistance and for the design of new therapeutic
      strategies.

PMID- 15158256
TI  - Nucleotide sequence and transcriptional analysis of the type A2 neurotoxin gene
      cluster in Clostridium botulinum.
AB  - The nucleotide sequences of the upstream regions of the botulinum neurotoxin type
      A1 (BoNT/A1) cluster of Clostridium botulinum strain NCTC 2916 and the BoNT/A2
      cluster of strain Kyoto-F were determined. A novel gene, designated orfx3, was
      identified following the orfx2 gene in both clusters. ORF-X2 and ORF-X3 exhibit
      similarity to the BoNT cluster associated P-47 protein. The BoNT/A1 and BoNT/A2
      clusters share a similar gene arrangement, but exhibit differences in the spacing
      between certain genes. Sequences with similarity to transposases were identified
      in these intergenic regions, suggesting that these differences arose from an
      ancestral insertion event. Transcriptional analysis of the BoNT/A2 cluster
      revealed that the genes of the cluster are primarily synthesized as three
      polycistronic transcripts. Two divergent polycistronic transcripts, one encoding
      the orfx1, orfx2, and orfx3 genes, the second encoding the p47, ntnh, and bont/a2
      genes, are transcribed from conserved BoNT cluster promoters. The third
      polycistronic transcript, expressed at low levels, encodes the positive
      regulatory botR gene and the orfx genes. This is the first complete analysis of a
      botulinum toxin A2 cluster.

PMID- 15158258
TI  - Effect of a pyruvate kinase (pykF-gene) knockout mutation on the control of gene
      expression and metabolic fluxes in Escherichia coli.
AB  - The metabolic regulation of Escherichia coli lacking a functional pykF gene was
      investigated based on gene expressions, enzyme activities, intracellular
      metabolite concentrations and the metabolic flux distribution obtained based on
      (13)C-labeling experiments. RT-PCR revealed that the glycolytic genes such as
      glk, pgi, pfkA and tpiA were down regulated, that ppc, pckA, maeB and mdh genes
      were strongly up-regulated, and that the oxidative pentose phosphate pathway
      genes such as zwf and gnd were significantly up-regulated in the pykF mutant. The
      catabolite repressor/activator gene fruR was up-regulated in the pykF mutant, but
      the adenylate cyclase gene cyaA was down-regulated indicating a decreased rate of
      glucose uptake. This was also ascertained by the degradation of ptsG mRNA, the
      gene for which was down-regulated in the pykF mutant. In general, the changes in
      enzyme activities more or less correlated with ratios of gene expression, while
      the changes in metabolic fluxes did not correlate with enzyme activities. For
      example, high flux ratios were obtained through the oxidative pentose phosphate
      pathway due to an increased concentration of glucose-6-phosphate rather than to
      favorable enzyme activity ratios. In contrast, due to decreased availability of
      pyruvate (and acetyl coenzyme A) in the pykF mutant compared with the wild type,
      low flux ratios were found through lactate and acetate forming pathways.

PMID- 15158257
TI  - Metabolic flux analysis for a ppc mutant Escherichia coli based on 13C-labelling
      experiments together with enzyme activity assays and intracellular metabolite
      measurements.
AB  - The physiology and central metabolism of a ppc mutant Escherichia coli were
      investigated based on the metabolic flux distribution obtained by (13)C-labelling
      experiments using gas chromatography-mass spectrometry (GC-MS) and 2-dimensional
      nuclear magnetic resonance (2D NMR) strategies together with enzyme activity
      assays and intracellular metabolite concentration measurements. Compared to the
      wild type, its ppc mutant excreted little acetate and produced less carbon
      dioxide at the expense of a slower growth rate and a lower glucose uptake rate.
      Consequently, an improvement of the biomass yield on glucose was observed in the
      ppc mutant. Enzyme activity measurements revealed that isocitrate lyase activity
      increased by more than 3-fold in the ppc mutant. Some TCA cycle enzymes such as
      citrate synthase, aconitase and malate dehydrogenase were also upregulated, but
      enzymes of glycolysis and the pentose phosphate pathway were downregulated. The
      intracellular intermediates in the glycolysis and the pentose phosphate pathway,
      therefore, accumulated, while acetyl coenzyme A and oxaloacetate concentrations
      decreased in the ppc mutant. The intracellular metabolic flux analysis uncovered
      that deletion of ppc resulted in the appearance of the glyoxylate shunt, with
      18.9% of the carbon flux being channeled via the glyoxylate shunt. However, the
      flux of the pentose phosphate pathway significantly decreased in the ppc mutant.

PMID- 15158259
TI  - Acquired resistance to bile increases fructose-6-phosphate phosphoketolase
      activity in Bifidobacterium.
AB  - Two Bifidobacterium strains with acquired resistance to bile were used in this
      study. Significant differences on membrane-associated protein profiles were found
      between the bile resistant derivatives and their corresponding original strains.
      One of the major species detected in one of the resistant derivatives had an
      apparent denatured molecular mass of approximately 90 kDa, and was identified as
      xylulose-5-phosphate/fructose-6-phosphate phosphoketolase, the key enzyme of
      Bifidobacterium carbohydrate catabolism. Phosphoketolase activity was
      considerably higher in membrane preparations and cell-free extracts of the two
      bile resistant derivatives. This correlated to a greater consumption rate of
      glucose in resistant strains. Fructose-6-phosphate phosphoketolase activity in
      the strain Bifidobacterium bifidum CECT4549 and its resistant derivative was
      found to be partially associated with the cytoplasmic membrane through weak
      interactions.

PMID- 15158260
TI  - Strain improvement for cephalosporin production by Acremonium chrysogenum using
      geneticin as a suitable transformation marker.
AB  - An Acremonium chrysogenum strain improvement program based on the transformation
      with cephalosporin biosynthetic genes was carried out to enhance cephalosporin C
      production. Best results were obtained with cefEF and cefG genes, selecting
      transformants with increased cephalosporin C production and lower accumulation of
      biosynthetic intermediates. Phleomycin resistant transformants, designated B1 and
      C1, showed a single copy random integration event, higher levels of cefEF
      transcript and, according to immunoblotting analyses, higher amounts of
      deacetylcephalosporin C acetyltransferase (DAC-AT) protein than their parental
      strains. Moreover, DAC-AT activity was higher in the transformants. Plasmids
      carrying geneticin resistance markers based on the nptII gene from Tn5 and the
      aphI gene from Tn903 were constructed to transform again B1 and C1, showing that
      the cassette Pgdh-nptII-trpC was able to confer geneticin resistance to A.
      chrysogenum and demonstrating that geneticin is a helpful selection marker.

PMID- 15158261
TI  - Hydroxylation of carbazoles by Aspergillus flavus VKM F-1024.
AB  - Carbazole was metabolized by Aspergillus flavus VKM F-1024 forming few
      monohydroxylated products. The structure of metabolites was determined by TLC,
      GC, MS and (1)H NMR analyses. 3-Hydroxycarbazole was revealed as a major
      bioconversion product, 1-hydroxy- and 2-hydroxycarbazoles were observed as minor
      products. In the presence of 1-benzoylindole, the hydroxylation position shifted
      toward preferable accumulation of 2-hydroxycarbazole and the formation of 2,6-
      and 2,7-dihydroxycarbazoles. This effect and microbial formation of these
      metabolites have never been reported before. At the conversion of N-acetyl- and N
      benzoylcarbazoles, carbazole was the major product, while 1-, 2- and 3
      monohydroxycarbazoles were formed in small amounts.

PMID- 15158262
TI  - Identification of an oxidative stress-sensitive protein from Campylobacter
      jejuni, homologous to rubredoxin oxidoreductase/rubrerythrin.
AB  - An oxidative stress-sensitive protein was found in the microaerophile
      Campylobacter jejuni. A novel 27-kDa protein was found to decrease concomitantly
      with a decrease in viability from either exogenous H(2)O(2) stress or endogenous
      oxidative stresses in aerobic conditions. Sequence analyses revealed that the 27
      kDa protein was identical to Cj0012c in C. jejuni NCTC11168 and its deduced 215
      amino acid sequence has similarity to two non-heme iron proteins found in other
      bacteria, rubredoxin oxidoreductase (Rbo) and rubrerythrin (Rbr). Thus, we
      designated the protein as Rrc (Rbo/Rbr-like protein of C. jejuni). In H(2)O(2)
      treated cells, Western blot analysis showed some bands smaller than Rrc, and RT
      PCR showed similar expression of Rrc mRNA to the control without treatment,
      suggesting that the sensitive response of Rrc to oxidative stress is due to
      degradation of the protein.

PMID- 15158263
TI  - Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium
      baratii isolated from human feces.
AB  - Ursodeoxycholic acid-producing bacteria are of clinical and industrial interest
      due to the multiple beneficial effects of this bile acid on human health. This
      work reports the first isolation of 7-epimerizing bacteria from feces of a
      healthy volunteer, on the basis of their capacity to epimerize the primary bile
      acid, chenodeoxycholic acid, to ursodeoxycholic acid. Five isolates were found to
      be active starting from unconjugated chenodeoxycholic acid and its tauro
      conjugated homologue, but none of these strains could epimerize the glyco
      conjugated form. Biochemical testing and 16S ribosomal DNA sequencing converged
      to show that all five isolates were closely related to Clostridium baratii (99%
      sequence similarity), suggesting that this bacterial species could be responsible
      at least partially, for this bioconversion in the human gut.

PMID- 15158264
TI  - Phosphorylation of glucosamine-6-phosphate synthase is important but not
      essential for germination and mycelial growth of Candida albicans.
AB  - A site-directed mutagenesis of the GFA1 gene encoding Candida albicans
      glucosamine-6-phosphate (GlcN-6-P) synthase afforded its GFA1S208A version. A
      product of the modified gene, lacking the putative phosphorylation site for
      protein kinase A (PKA), exhibited all the basic properties identical to those of
      the wild-type enzyme but was no longer a substrate for PKA. Comparison of the C.
      albicans Deltagfa1/GFA1 and Deltagfa1/GFA1S208A cells, grown under conditions
      stimulating yeast-to-mycelia transformation, revealed that the latter
      demonstrated lower GlcN-6-P synthase specific activity, decreased chitin content
      and formed much fewer mycelial forms. All these findings, as well as the observed
      effects of specific inhibitors of protein kinases, suggest that a loss of the
      possibility of GlcN-6-P synthase phosphorylation by PKA strongly reduces but not
      completely eliminates the germinative response of C. albicans cells.

PMID- 15158265
TI  - The release of secretory vesicle in encysting Giardia lamblia.
AB  - Giardia is an intestinal parasite that undergoes adaptation for survival outside
      the host. It secretes an extracellular cyst wall using a poorly understood
      process. An encystation-specific secretory vesicle (ESV) was previously described
      containing cyst wall proteins. The process of release of these vesicles has been
      suggested to occur after fragmentation of large ESV in small secretory vesicles,
      followed by exocytosis, but it was not demonstrated. The release of the ESV was
      studied by transmission electron microscopy. It was observed: (1) the moment of
      vesicle release; (2) that a large vesicle is exocytosed and does not fragment
      into small vesicles; (3) membrane fusion is distinct from traditional exocytosis
      since it is incomplete; (4) the occurrence of membrane fragmentation and that
      those membranes reseal to form ghosts; (5) these membrane ghosts may be
      endocytosed, adhered to flagellar surface or/and form empty vesicles in the
      extracellular medium.

PMID- 15158266
TI  - Generation of Leishmania mutants lacking antibiotic resistance genes using a
      versatile hit-and-run targeting strategy.
AB  - The development of a method to create defined mutants of Leishmania parasites
      lacking foreign genes conferring resistance to antibiotics has both experimental
      and practical applications. Mutants deficient in specific virulence genes have
      potential as attenuated live vaccines, but these can only be of clinical
      relevance if the antibiotic resistance genes used for selection of the mutants
      are subsequently removed. In addition, the limited number of antibiotic
      resistance genes that can be used for genetic manipulation of Leishmania means
      that a system for recycling them for subsequent use would be highly beneficial
      when multiple genetic modifications are wanted. In the method we report here, a
      cassette carrying in tandem the hygromycin resistance gene as a positive marker
      and thymidine kinase gene as a negative marker is first integrated into the locus
      of interest and then replaced by a null targeting fragment containing no
      exogenous DNA. The application of this hit-and-run strategy for removal of one
      allele of the CPB cysteine peptidase gene array of Leishmania infantum is
      described.

PMID- 15158267
TI  - An origin for arsenobetaine involving bacterial formation of an arsenic-carbon
      bond.
AB  - Lysed-cell extract of a Pseudomonas sp. was shown to catalyse bioconversion of
      dimethylarsinoylacetate to arsenobetaine and dimethylarsinate. Provision of the
      universal methyl donor S-adenosylmethionine to bioconversion mixtures promoted
      both the rate and extent of arsenobetaine formation. These findings suggest that
      in the proposed biosynthesis of arsenobetaine from dimethylarsinoylethanol,
      oxidation (i.e. the formation of the carboxymethyl group of
      dimethylarsinoylacetate) would precede the reduction and methylation at the
      arsenic atom. The presence of enzyme(s) capable of methylating
      dimethylarsinoylacetate in a bacterial isolate from marine mussel (Mylitus
      edulis), highlights a possible direct involvement of prokaryotic organisms in the
      biosynthesis of organoarsenic compounds within marine animals.

PMID- 15158268
TI  - Characterisation and expression of a gene encoding a mutarotase from the fungus
      Rhizopus nigricans.
AB  - A gene coding for a mutarotase was isolated and characterised from the
      filamentous fungus Rhizopus nigricans. In order to determine the encoded enzyme's
      activity a recombinant protein was prepared in the baculovirus expression system
      and the mutarotase activity was determined. Expression studies showed that the
      gene is repressed by high as well as low concentrations of glucose and
      derepressed during deficiency of glucose. Besides the regulation at the level of
      transcription, an accelerative effect of glucose in growth medium on the
      mutarotase mRNA decay was also demonstrated. Moreover, a Southern hybridisation
      performed at lower temperatures suggested that the R. nigricans genome harbours a
      nucleotide sequence, that is homologous to the isolated gene.

PMID- 15158269
TI  - Tuber aestivum and Tuber uncinatum: two morphotypes or two species?
AB  - Tuber spp. are ectomycorrhizal fungi that establish symbioses with shrubs and
      trees. Because of their different smell and taste, Tuber uncinatum and Tuber
      aestivum are two truffle morphotypes with a different market value, but whether
      or not T. uncinatum and T. aestivum are different taxa is still an open debate
      among mycologists. In order to identify molecular keys characterizing both T.
      aestivum and T. uncinatum morphotypes, ITS/RFLPs analyses were carried out on a
      large collection of samples from all over Italy and from other European
      countries, followed by a study of the phylogenesis of ITS, beta-tubulin and EF 1
      alpha genes, on representative samples. The present study provides compelling
      evidence that: (i) T. uncinatum and T. aestivum belong to the same species, (ii)
      neither morphotype presents a specific molecular fingerprint, but they may even
      share identical alleles at any of the loci analysed; (iii) T. aestivum is most
      likely under a selfing reproductive mode. Our findings suggest that ecological,
      rather than genetic causes may account for differences in sporal morphology,
      taste and smell between T. aestivum and T. uncinatum truffles.

PMID- 15158270
TI  - Identification Leptospira santarosai serovar shermani specific sequences by
      suppression subtractive hybridization.
AB  - In Taiwan, leptospirosis is caused mainly by Leptospira santarosai serovar
      shermani. Suppression subtractive hybridization was employed to isolate DNA
      fragments present in pathogenic L. santarosai serovar shermani but absent in non
      pathogenic L. biflexa serovar patoc. Analysis of 23 subtracted DNA clones
      revealed 25 gene fragments by BLASTX program. Eight clones showed similarity to
      transposase genes and three clones displayed homology with either translation or
      metabolism related genes. Four clones were similar to outer membrane protein,
      penicillin-binding protein, CreD-like protein and the protein of two-component
      signal transduction system, respectively. One clone had TPR repeat domain and
      five clones had significant similarity with hypothetical proteins of unknown
      functions. The remaining four clones exhibited no homology with any known genes.
      These results indicate that subtractive hybridization can successfully identify
      genes that are absent from the non-pathogenic Leptospira and provide a starting
      point for clarifying the differential genes expression between pathogenic and non
      pathogenic Leptospira species.

PMID- 15158271
TI  - Inhibition of plant protein synthesis by the cyanobacterial hepatotoxin,
      cylindrospermopsin.
AB  - Cylindrospermopsin, a cyanobacterial guanidine alkaloid hepatotoxin and protein
      synthesis-inhibitor, was assayed for its effects on the germination of pollen
      from tobacco (Nicotiana tabacum cv Samsun NN). Pollen germination, measured by
      Alcian Blue dye-binding, was inhibited by cylindrospermopsin between 5 and 1000
      microg ml(-1). As a protein synthesis-inhibitor, cylindrospermopsin did not
      inhibit pollen germination to the same extent as cycloheximide on a gravimetric
      basis, but significantly reduced the amount of (14)C-(U)-l-leucine labelling in
      pollen tubes. The inhibition of tobacco pollen germination may be amenable for
      development as a bioassay for cylindrospermopsin, although this would require a
      pre-concentration step for the monitoring of environmental samples. Implications
      of these observations for current spray-irrigation practices are discussed.

PMID- 15158272
TI  - Expression from the Escherichia coli dapA promoter is regulated by intracellular
      levels of diaminopimelic acid.
AB  - Dihydropicolinate synthase (DHDPS; E.C. 4.2.1.52) catalyses the first committed
      step of lysine biosynthesis in plants and bacteria. Plant DHDPS enzymes, which
      are responsible solely for lysine biosynthesis, are strongly inhibited by lysine
      (I0.5 =10 microM), whereas the bacterial enzymes which are less responsive or
      insensitive to lysine inhibition have the additional function of meso
      diaminopimelate biosynthesis which is required for cell wall formation. Previous
      studies have suggested that expression of the Escherichia coli dapA gene,
      encoding DHDPS, is unregulated. We show here that this is not the case and that
      expression of LacZ from the dapA promoter (PdapA) increases in response to
      diaminopimelic acid limitation in E. coli K-12.

PMID- 15158273
TI  - Maturation of the murine cecal microbiota as revealed by terminal restriction
      fragment length polymorphism and 16S rRNA gene clone libraries.
AB  - The maturation of murine cecal microbiota was determined by terminal restriction
      fragment polymorphism (T-RFLP) and 16S rRNA gene clone libraries. Cecal
      microbiota in specific pathogen free (SPF) mice aged four to 10 weeks were
      collected. The cluster of samples in 4-week-old mice was different from those of
      other ages based on T-RFLP profiles. The majority of clones obtained in this
      study belonged to the Clostridium coccoides (C. coccoides) group, the Bacteroides
      group or the Lactobacillus group. Phylogenetic analysis showed characteristic
      clusters composed of new operational taxonomic unit (OTU) of the C. coccoides and
      Bacteroides groups. The existence of a large number of yet unidentified bacteria
      inhabiting the murine cecum was demonstrated by 16S rRNA gene clone libraries. T
      RFLP analysis data were more complex and more sensitive than the patterns
      generated by computer simulation of 16S rRNA gene clone library analysis data. T
      RFLP revealed development with maturation of cecal microbiota including
      unidentified bacteria of SPF mice.

PMID- 15158274
TI  - CreA-mediated carbon catabolite repression of beta-galactosidase formation in
      Aspergillus nidulans is growth rate dependent.
AB  - Carbon catabolite repression by the CreA-transcriptional repressor is widespread
      in filamentous fungi, but the mechanism by which glucose triggers carbon
      catabolite repression is still poorly understood. We investigated the hypothesis
      that the growth rate on glucose may control CreA-dependent carbon catabolite
      repression by using glucose-limited chemostat cultures and the intracellular beta
      galactosidase activity of Aspergillus nidulans, which is repressed by glucose, as
      a model system. Chemostat cultures at four different dilution rates (D = 0.095,
      0.068, 0.045 and 0.015 h-1) showed that formation of beta-galactosidase activity
      is repressed at the two highest Ds, but increasingly derepressed at the lower Ds,
      the activity at 0.015 h-1 equalling that in derepressed batch cultures. Chemostat
      cultures with the carbon catabolite derepressed A. nidulans mutant strain
      creADelta4 revealed a dilution-rate independent constant beta-galactosidase
      activity of the same range as that found in the wild-type strain at D = 0.015 h
      1. Two other enzymes--isocitrate lyase, which is almost absent on glucose due to
      a CreA-independent mechanism; and galactokinase, which is formed constitutively
      and independent of CreA--were measured as controls. They were formed at constant
      activity at each dilution rate, both in the wild-type strain as well as in the
      carbon catabolite derepressed mutant strain. We conclude that the growth rate on
      glucose is a determinant of carbon catabolite repression in A. nidulans, and that
      below a certain growth rate carbon catabolite derepression occurs.

PMID- 15158275
TI  - Biochemical requirements for PCBCK1 kinase activity, the Pneumocystis carinii
      MEKK involved in cell wall integrity.
AB  - Fungal cell wall assembly is a complicated process involving multiple enzymes and
      coordinated signaling pathways. The cell wall integrity MAPK pathway acts to
      stabilize the fungal cell wall during conditions of elevated temperature by
      regulation of glucan synthesis. The upstream kinase, BCK1, is a critical
      component of this pathway. Pneumonia is a significant cause of death from the
      fungal opportunistic pathogen Pneumocystis in immunocompromised states,
      especially with HIV infection. We have previously shown that PCBCK1 functions in
      the cell wall integrity pathway in yeast as a functional protein kinase. Kinases
      have specific requirements for enzymatic function which have not been
      investigated in fungi. Here we examine the biochemical requirements for PCBCK1
      kinase activity expressed in Saccharomyces cerevisiae bck1Delta yeast. PCBCK1
      requires 10 mM MgCl(2), pH 6, temperature 30 degrees C, and 10 microM ATP for
      kinase activity. Interference of the Pneumocystis cell wall integrity pathway is
      an attractive target for drug development since glucan synthesis machinery is not
      present in humans.

PMID- 15158276
TI  - Enzymes used for the determination of HbA1C.
AB  - To develop an enzymatic measurement of HbA(1C), two key enzymes, i.e., fructosyl
      peptide oxidase and Aspergillus protease were characterized. Fructosyl peptide
      oxidase from Eupenicillium terrenum was a flavoenzyme that could catalyze the
      oxidation of N-(1-deoxyfructosyl)-Val-His. The enzyme showed high specificity
      toward alpha-glycated molecules, therefore it seemed suitable for the HbA(1C)
      assay. Since high levels of FPOX expression seemed toxic to host cells, we
      applied a gene expression system using a bacteriophage vector and achieved high
      levels of expression in Escherichia coli. Next, we found that Aspergillus
      protease was able to digest N-(1-deoxyfructosyl)-hexapeptide, a glycated peptide
      that was released from the beta-chain of HbA(1C) by Glu-C endoproteinase. We
      showed that the N-(1-deoxyfructosyl)-Val-His released from N-(1-deoxyfructosyl)
      hexapeptide by Aspergillus protease could be assayed enzymatically using
      fructosyl peptide oxidase, therefore these enzymes could be applied to the
      enzymatic measurement of HbA(1C).

PMID- 15158277
TI  - CO2 reduction to the level of formylmethanofuran in Methanosarcina barkeri is non
      energy driven when CO is the electron donor.
AB  - A Methanosarcina barkeri mutant lacking Ech hydrogenase does not catalyze CH(4)
      formation from H(2)/CO(2) since, as was shown previously, the energy-driven
      reduction of CO(2) to formylmethanofuran by H(2) is blocked. CH(4) formation by
      this mutant could be restored in the presence of CO or pyruvate. Furthermore,
      CH(4) formation from H(2)/CO(2) plus CO by the Deltaech mutant was not inhibited
      by the protonophore TCS. These data show that in vivo the reduction of CO(2) to
      formylmethanofuran can be coupled to the oxidation of CO or pyruvate via a common
      electron carrier and that the reduction of this electron carrier by H(2),
      catalyzed by Ech hydrogenase, is the energy-driven step in formylmethanofuran
      synthesis from CO(2), H(2) and methanofuran.

PMID- 15158278
TI  - Cloning and functional characterization of the Rhizopus oryzae high affinity iron
      permease (rFTR1) gene.
AB  - Rhizopus oryzae is the most common etiologic agent of mucormycosis. Clinical and
      animal model data clearly demonstrate that the presence of elevated available
      serum iron predisposes the host to develop mucormycosis. Therefore, the high
      affinity iron permease (rFTR1) which encodes a protein required to scavenge iron
      from the environment, is highly likely to be a critical determinant of virulence
      for R. oryzae. We have cloned rFTR1 by using a PCR approach relying on degenerate
      primers designed from the conserved regions of Saccharomyces cerevisiae high
      affinity iron permease. Sequence analysis of a 2.0 kb EcoRI genomic clone
      revealed a single open reading frame of 1107 bp that lacked introns. The putative
      rFtr1p had significant homology to known fungal high affinity iron permeases from
      Candida albicans (46% identity) and S. cerevisiae (44% identity). In R. oryzae,
      rFTR1 was expressed in iron-depleted and not in iron-rich media. Finally, rFTR1
      restored the ability of an ftr1 null mutant of S. cerevisiae to grow on iron
      limited medium and to take up radiolabeled iron, whereas S. cerevisiae
      transformed with the empty vector did not. These data demonstrate that we have
      cloned the gene encoding a R. oryzae high affinity iron permease and the putative
      rFtr1p is involved in assimilation of iron from iron-depleted environments.

PMID- 15158279
TI  - Differential transcription of beta-glucosidase and cellobiose dehydrogenase genes
      in cellulose degradation by the basidiomycete Phanerochaete chrysosporium.
AB  - Transcriptional analysis of beta-glucosidase gene (bgl) and cellobiose
      dehydrogenase gene (cdh) in relation to cellobiose metabolism in the
      basidiomycete Phanerochaete chrysosporium was performed using real-time
      quantitative RT-PCR. Addition of glucose to cellulose-degrading culture
      significantly decreased the number of both transcripts. In contrast, addition of
      cellobiose repressed only transcription of bgl but no effect for that of cdh.
      Moreover, to investigate induction of the two genes, the mycelia grown on glucose
      medium were transferred to medium containing glucose, cellobiose or no carbon
      source. In cellobiose medium, the number of bgl transcripts was slightly lower,
      whereas that of cdh transcripts was 2.3-fold higher than those in glucose medium.
      Consequently, cellobiose represses transcription of bgl, whereas it induces that
      of cdh.

PMID- 15158280
TI  - Design of 16S rRNA-targeted oligonucleotide probes and microbial community
      analysis in the denitrification process of a saline industrial wastewater
      treatment system.
AB  - Three 16S rRNA-targeted oligonucleotide probes, namely, PSMg437 targeting several
      members of the genus Pseudomonas, Hlm474 targeting several members of the genus
      Halomonas, and Clw844 targeting several members of the genus Colwellia, were
      designed. The microbial community structure and nitrogen removal ability of
      nitrate-containing saline wastewater treatment systems with anaerobic packed bed
      and fluidized bed were monitored. Direct cell counting using fluorescence in situ
      hybridization (FISH) images revealed that various phylogenetic groups were evenly
      distributed in the anaerobic packed bed whereas members of the genus Halomonas
      were dominant particularly in the anaerobic fluidized bed. These results suggest
      that the microbial communities produced by different flow conditions correlated
      with denitrification ability in saline industrial wastewater treatment systems.

PMID- 15158281
TI  - Tubercle bacilli generate a novel cell wall-associated pigment after long-term
      anaerobic culture.
AB  - Many cases of tuberculosis result from reactivation of previously acquired latent
      infections. Models to study such persister forms often involve gradual depletion
      of oxygen during culture as poor aeration is a characteristic of non-progressive
      TB granulomas. Anaerobically cultured bacilli develop a thickened outer-most cell
      wall layer. Here, we analyzed this layer from anaerobically cultured
      Mycobacterium tuberculosis and Mycobacterium bovis BCG. By six weeks of
      anaerobiosis a pigment was detected at levels > 60-fold higher in anaerobic than
      aerobic bacilli. This pigment was responsible for the electron-dense appearance
      of the thickened cell wall layer and gave an electrospray mass spectrometry peak
      at 409 Da (M+Na)+ or (M+H)+. We termed this pigment APP1, anaerobically produced
      pigment 1, the first pigment identified in M. tuberculosis.

PMID- 15158283
TI  - The role of off-farm employment in tropical forest conservation: labor,
      migration, and smallholder attitudes toward land in western Uganda.
AB  - The potential for off-farm employment (OFE) to contribute significantly to forest
      conservation in the tropics is a widely held logic among donors, governments, and
      social scientists. While an aggregate level examination of OFE cases can support
      this logic, there is disagreement as to the operative aspects of specific
      linkages and assumptions. This study examines the case of the tea industry in
      western Uganda, and uses a combination of fieldwork and remote sensing to pursue
      a more nuanced examination of the role of migration and non-monetary aspects of
      OFE on forest conservation in both a national park and unprotected forest
      contexts. Results indicate that the tea industry does serve as an off-farm
      employer to a limited number of local smallholders but these benefits are offset
      by the industry's overwhelming dependence on migrant labor which sees OFE as
      temporary, then seeks to settle locally. There is also evidence that the tea
      industry is contributing to conservation efforts of Kibale National Park by
      unintentionally serving as a physical buffer zone, which inhibits both human
      encroachment on the park and wildlife encroachment on smallholder crops. The
      latter represents a site-specific phenomenon that holds much potential for future
      management plans of the area and exemplifies the importance of considering the
      site-specific circumstances associated with OFE development.

PMID- 15158284
TI  - Abatement cost curves: a viable management tool for enabling the achievement of
      win-win waste reduction strategies?
AB  - Environmental regulation of industrial activity is generally believed to have a
      negative impact on the industry. Recent literature has suggested, however, that
      reducing industrial waste outputs can, in some circumstances, result in a 'win
      win', or at least 'win-draw', scenario for industry and the environment. The
      viability of using the abatement cost curve method as a management tool to enable
      the achievement of a 'win-win' state is investigated here. Copper pollution in
      the Humber Estuary is used as a case-study, and the abatement cost curve
      methodology proves to be a valuable tool in identifying barriers to achieving the
      win-win state, and also in providing future direction for the waste management
      strategy. Abatement cost curves are concluded to be powerful management tools
      which greatly improve the transparency of waste reduction information.

PMID- 15158282
TI  - Transcriptional analysis and operon structure of the tagA-orf2-orf3-mop-tagD
      region on the Vibrio pathogenicity island in epidemic V. cholerae.
AB  - The Vibrio pathogenicity island (VPI) in epidemic Vibrio cholerae is an essential
      virulence gene cluster. The VPI can excise from the chromosome and form
      extrachromosomal circular excision products. The VPI is 41.2-kb in size and
      encodes 29 potential proteins, several of which have no known function and whose
      regulation is not well understood. To determine the transcriptional organization
      of the tagA-orf2-orf3-mop-tagD region located at the 5'-(left) end of the VPI, we
      used reverse-transcriptase-PCR (RT-PCR), Northern blot analysis and DNA
      sequencing. RT-PCR primers were designed to transcribe and amplify regions
      spanning two or more open reading frames so as to establish the transcriptional
      organization. RT-PCR and Northern blot results demonstrated that the tagA-tagD
      region is transcribed as a polycistronic message and organized into several
      potential operons including tagA-orf2, orf3-mop, orf3-mop-tagD and tagD alone.
      Transcriptional lacZ fusions supported the existence of a promoter upstream of
      orf3 that was toxT-dependent. Interestingly, our data suggests that the orf3
      promoter can drive the expression of either a long transcript (orf3-mop-tagD) or
      a short transcript (orf3-mop) without tagD. Our data also suggests that tagD can
      be expressed from two different promoters and that tagD is either transcribed
      alone or co-expressed with orf3-mop under certain conditions. These studies
      provide new insight into the genetic structure, transcriptional organization and
      regulation of a cluster of virulence genes on the VPI of epidemic V. cholerae.

PMID- 15158285
TI  - Azadirachta indica leaf powder as an effective biosorbent for dyes: a case study
      with aqueous Congo Red solutions.
AB  - In the present work, the leaves of Azadirachta indica (locally known as the Neem
      tree) in the form of a powder were investigated as a biosorbent of dyes taking
      aqueous Congo Red solution as a model system. The sorbent was made from mature
      Neem leaves and was investigated in a batch reactor under variable system
      parameters such as concentration of the aqueous dye solution, agitation time,
      adsorbent amount, pH, and temperature. An amount of 0.6 g of the Neem leaf powder
      (NLP) per litre could remove 52.0-99.0% of the dye from an aqueous solution of
      concentration 2.87 x 10(-2) mmol l(-1) with the agitation time increasing from 60
      to 300 min. The interactions were tested with respect to both pseudo first-order
      and second-order reaction kinetics; the latter was found to be more suitable.
      Considerable intra-particle diffusion was found to occur simultaneously. The
      sorption process was in conformity with Langmuir and Freundlich isotherms
      yielding values of the adsorption coefficients in the following ranges:
      Freundlich n: 0.12-0.19, Kf: 0.1039-0.2648 L g(-1); Langmuir qm: 41.24-128.26 g
      kg(-1), b: 443.3-1898.0 l mmol(-1), which supported favourable adsorption. The
      Langmuir monolayer capacity (qm) was high and the values of the coefficient b
      indicated the equilibrium, dye + NLP = dye...NLP being shifted overwhelmingly
      towards adsorption. Thermodynamically, the sorption process was exothermic with
      an average heat of adsorption of -12.75 kJ mol(-1). The spontaneity of the
      sorption process was also confirmed by the favourable values of Gibbs energy
      (mean values: -1.09 to -1.81 kJ mol(-1)) and entropy of adsorption (range: -18.97
      to -56.32 J mol(-1)K(-1)). The results point to the effectiveness of the Neem
      leaf powder as a biosorbent for removing dyes like Congo Red from water.

PMID- 15158286
TI  - Landscape changes in agrarian landscapes in the 1990s: the interaction between
      farmers and the farmed landscape. A case study from Jutland, Denmark.
AB  - Recent landscape changes in a farmed landscape are analysed and related to farm
      and farmer characteristics. It is assumed that farm and farmer characteristics
      serve as mediators of large scale or macro driving forces of change-in the
      present case, a changing farming context including demands for a more
      environmentally friendly farming practise and a reduced output. The results are
      based on multivariate analyses of data collected from structured interviews of
      160 farmers in a case study area, in central Jutland, measuring 5000 ha. The
      analysis shows that farmers are highly involved in landscape changes. The
      investigated landscape changes include creation and removal of landscape elements
      as well as certain management changes. The most common activity was creation of
      elements: hedgerows, small woodlands and conversion of rotational arable land to
      permanent grassland, whereas removal of elements, mainly hedgerows and semi
      natural grasslands, were seen less frequently. Management changes like
      abandonment of permanent grassland were widespread. The results indicate a
      general extensification of the land use and the authors interpret the results
      partly as an indication of a change from productivism to a more multifunctional
      agricultural regime. The observed landscape changes at the farm level show a low,
      but structured relationship with the current farm and farmer characteristics,
      meaning that landscape changes were undertaken by various farmers and on various
      farms. On a general level, however, the age of the farmer and the duration of
      farm ownership seem to have a major influence on the landscape changes.

PMID- 15158288
TI  - Tradeable hunting obligations--a new approach to regulating red deer numbers in
      the Scottish Highlands?
AB  - The population of red deer (Cervus elaphus) in Scotland has doubled over the last
      30 years and there is increasing concern among conservationists about the long
      term impact of increased grazing on native woodlands and other sensitive nature
      conservation sites. Currently, the government relies on a voluntary approach to
      deer control, but landowners seem unable or unwilling to shoot sufficient numbers
      to meet cull targets. The aim of this paper is to examine alternatives to the
      'voluntary approach' supported by insights from a mail questionnaire of
      landowners and recreational hunters. In principle, subsidies or taxation is
      possible but the Deer Commission for Scotland, the government agency responsible,
      has neither the necessary funding or the legislative power to introduce such a
      scheme. A tradable culling 'obligations' system on the other hand would build on
      the voluntary principle by allowing individual landowners to 'trade' culling
      obligations to neighbouring estates. Compared to traditional regulatory
      approaches, they are less bureaucratic and inefficient and have the potential to
      meet environmental targets at least cost as landowners can trade their culling
      obligation to another estate or hunting club should they wish to do so. Overall,
      the State's role would be restricted to setting the annual cull and the
      administration of the permit system for which a small charge could be levied per
      deer.

PMID- 15158289
TI  - Cumulative environmental impacts and integrated coastal management: the case of
      Xiamen, China.
AB  - This paper examines the assessment of cumulative environmental impacts and the
      implementation of integrated coastal management within the harbour of Xiamen,
      China, an urban region in which the coastal zone is under increasing pressure as
      a result of very rapid economic growth. The first stage of analysis incorporates
      components of a cumulative effects assessment, including (a) identification of
      sources of environmental impacts, notably industrial expansion, port development,
      shipping, waste disposal, aquaculture and coastal construction, (b) selection of
      a set of valued ecosystem components, focusing on circulation and siltation,
      water quality, sediment, the benthic community, and mangrove forests, and (c) use
      of a set of key indicators to examine cumulative impacts arising from the
      aggregate of human activities. In the second stage of analysis, the paper
      describes and assesses the development of an institutional framework for
      integrated coastal management in Xiamen, one that combines policy and planning
      (including legislative and enforcement mechanisms) with scientific and monitoring
      mechanisms (including an innovative 'marine functional zoning' system). The paper
      concludes that the integrated coastal management framework in Xiamen has met all
      relevant requirements for 'integration' as laid out in the literature, and has
      explicitly incorporated consideration of cumulative impacts within its management
      and monitoring processes.

PMID- 15158287
TI  - Feasibility versus sustainability in urban water management.
AB  - Decision making in urban water management is exemplified by the case of Austria:
      Although researchers define a comprehensible concept of sustainability,
      practitioners emphasize feasibility and accept limitations in sustainability.
      Could the specification of particular methods, chosen from some decision support
      methodology, remedy this situation? While an integrative assessment of
      sustainability should not be based on prescribed or standardized criteria, or
      even a certain assessment method, it should force the decision makers to make
      their chosen premise more visible. To this end a change of the decision making
      process is proposed, which will allow the decision makers to adapt the decision
      making process to the circumstances of a specific project in a way that is
      accepted by the stakeholders.

PMID- 15158290
TI  - Effect of pre-hydrolysis on floc structure.
AB  - Morphological changes in flocs were elucidated by small-angle light scattering,
      free settling tests and microscopic observation to determine the effects of pre
      hydrolysis (alkaline treatment and ultrasonication) on two sludges--primary raw
      sludge from the Malabar Sewage Treatment Plant, Sydney (sludge M) and biological
      sludge collected at the nitrogen removal unit of St Marys Sewage Treatment Plant
      in Sydney (sludge S). Ultrasonication or alkaline treatment released a marked
      amount of insoluble organic matter in a soluble form. The latter treatment was
      more efficient than the former. Meanwhile, the pre-hydrolyzed flocs had more
      compact structures than the original ones, as shown by their higher free-settling
      fractal dimension, lower areal porosity and smaller internal pores. In
      particular, alkaline treatment yielded flocs with more compact interiors than did
      ultrasonication. Such detailed structural information could not be elicited by
      monitoring the change in floc size. The greater resistance to mass transfer of
      the hydrolyzed flocs thus produced does not reduce the efficiency of subsequent
      digestion, indicating that the surface reaction rate on the solid surface might
      have dominated since the pre-hydrolysis steps modified the local chemical
      environment to promote digestion.

PMID- 15158291
TI  - Obesity epidemics: secular trend or globalization consequence? Beyond the
      interaction between genetic and environmental factors.

PMID- 15158292
TI  - Management of diabetes in childhood: are children small adults?
AB  - Diabetes in childhood is the most common chronic disease and generally fits the
      type 1 category, even though other forms of non-autoimmune diabetes are now
      emerging in this age. At variance with adults, children and adolescents undergo
      physiological process, which may frequently require adjustments of clinical
      management of diabetes. Moreover, the hormonal and psychological changes during
      puberty may be crucial in conditioning management. Furthermore, common illnesses
      frequently affecting children may also destabilise metabolic control.
      Consequently, education in children is the cornerstone of treatment. This review
      focuses on the several and peculiar aspects of practical management of diabetes
      in paediatric age, which require professional figures such as paediatricians,
      nurses, dieticians, psychologists, social assistants originally trained in
      paediatric area, able to deal with the age-related medical, educational,
      nutritional and behavioural issues of diabetes.

PMID- 15158293
TI  - Higher calorie prescription improves nutrient delivery during the first 5 days of
      enteral nutrition.
AB  - AIMS: It is unclear whether prescribing a higher amount of calories by enteral
      nutrition (EN) increases actual delivery. This prospective controlled study aimed
      at comparing the progression of EN of two study populations with different levels
      of calorie prescriptions, during the first 5 days of EN. METHODS: The daily
      calorie prescription of group 1 (n=346) was 25 and 20 kcal/kg body weight for
      women <60 and > or =60 years, respectively, and 30 and 25 kcal/kg body weight for
      men <60 and > or =60 years, respectively. The prescription of group 2 (n=148) was
      5 kcal/kg body weight higher than in group 1. Calorie intakes were expressed as
      percentage of resting energy expenditure (REE) and protein intakes as percentage
      of requirements estimated as 1.2 g/kg body weight/day. Patients were classified
      as <60 and > or =60 years and as medical or surgical patients. Statistical
      analysis was performed with ANOVA for repeated measures. RESULTS: Calorie and
      protein deliveries increased in both groups independently of age and ward
      categories (P< or =0.0001). Group 2 showed faster progressions of calorie and
      protein intakes than group 1 in patients altogether (P< or =0.002), > or =60
      years (P< or =0.01) and in surgical patients (P< or =0.02). Differences of
      calorie and protein intakes between day 1 and day 5 were significantly higher in
      group 2 than group 1 for patients altogether (75+/-61 vs. 56+/-54% of REE; 41+/
      30 vs. 31+/-/-27% of protein requirements), those over 60 years (76+/-67 of REE
      vs. 52+/-59 of protein requirements) and surgical patients (81+/-52 vs. 58+/-57%
      of REE; 44+/-27 vs. 33+/-29% of protein requirements). CONCLUSIONS: Increasing
      the levels of EN prescriptions improved calorie and protein deliveries. While the
      mean energy delivery over 5 days was sufficient to cover requirements, the
      protein delivery by EN was insufficient, despite our nutritional support team.

PMID- 15158294
TI  - Effect of chronic renal failure with metabolic acidosis on alanine metabolism in
      isolated liver cells.
AB  - BACKGROUND & AIMS: Decreased ureagenesis and gluconeogenesis from alanine have
      been reported during chronic renal failure in rat. This study addressed the
      respective roles of plasma-membrane transport and intracellular metabolism in
      these abnormalities of alanine pathways. METHODS: In hepatocytes isolated from
      uremic and control rats, we investigated: (1) the influence of uremia on
      gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics
      of alanine plasma-membrane transport; (3) the relationships between intracellular
      alanine concentrations and its metabolism. Plasma-membrane alanine transport was
      assessed after addition of alanine (2 mM) by measuring its intracellular
      accumulation from 0 to 10 min, in the presence of a transaminase inhibitor.
      Alanine metabolism was studied in perifused hepatocytes by measuring
      intracellular alanine concentration together with urea, glucose and lactate
      production in the presence of increasing concentrations of alanine (0-8 mM).
      RESULTS: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05)
      a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma
      membrane transport decreased by 20% during uremia. During perifusions, uremia
      induced a 30-40% decrease in urea, glucose, and lactate production without
      modifying intracellular alanine concentration. CONCLUSIONS: In uremic rats with
      acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane
      transport and intracellular transamination steps.

PMID- 15158295
TI  - Perioperative administration of parenteral fish oil supplements in a routine
      clinical setting improves patient outcome after major abdominal surgery.
AB  - BACKGROUND & AIMS: It is hypothesized that provision of pre- and/or postoperative
      omega-3 fatty acids to surgical patients in clinical routine improves clinical
      outcome. METHODS: Retrospective evaluation of a 2-year-longitudinal data base of
      ICU patients (n=249) elected for major abdominal surgery. Group I (n=110):
      postoperative standard parenteral nutrition (1.2 g amino acids, 0.3 g glutamine
      dipeptide, 0.6 g lipids, 4 g/kg glucose; energy ratio glucose to lipid 2:1);
      group II (n=86): part of postoperative lipid emulsion replaced by fish oil; group
      III (n=53): in addition 2-3 days preoperative fish oil supplementation (max. 100
      ml/d). RESULTS: A decrease in mortality was observed in group III compared to
      group I (P=0.02). The number of patients requiring mechanical ventilation was
      lower with perioperative fish oil (n=34 in groups I and II. 10 in III, P<0.05).
      The number of days in ICU was not different (group I: 7.6 days, group II: 7.0,
      group III: 7.3), the length of hospital stay was shorter in group I (group I:
      29.2 days, group II: 24.9, group III: 22.2, P<0.05 vs I). CONCLUSIONS: In a
      retrospective evaluation, perioperative provision of parenteral fish oil (ca. 10
      g/day) beneficially influences patient outcome probably by modulating the immune
      response.

PMID- 15158296
TI  - Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in
      mild hypercholesterolaemic individuals.
AB  - BACKGROUND: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc
      FOS) has been shown to increase significantly bifidus counts and to produce high
      amounts of short-chain fatty acids (SCFA), presumed to influence glucose and
      lipid metabolism. AIM: To evaluate the effects of moderate intake of sc-FOS on
      glucose and lipid metabolism in individuals with mild hypercholesterolaemia.
      DESIGN: A randomized double-blind sequential cross-over study. SUBJECTS AND
      METHODS: Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years
      (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l
      and plasma triglycerides <3.45 mmol/l, participated in the study. The study was
      performed after a wash-out period of 1 month and a run-in period of 1 month to
      stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20
      g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run
      in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or
      placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a
      duration of 2 months and thereafter switched to the other treatment for
      additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL)
      cholesterol and triglyceride concentrations were measured in the fasting state at
      the end of run-in and of each treatment period. At the end of the two treatment
      periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%,
      fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo;
      plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the
      test meal were evaluated. RESULTS: No significant difference in fasting
      parameters was detected between the two treatments. After sc-FOS and placebo
      plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l
      (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.).
      No significant differences were observed in cholesterol and triglyceride content
      of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma
      Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/
      35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were
      not significantly different between sc-FOS and placebo, while postprandial
      insulin response (incremental area) was significantly reduced after sc-FOS
      compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02).
      CONCLUSIONS: A moderate intake of sc-FOS has no major effects on lipid
      metabolism, both in the fasting and in the postprandial period, in individuals
      with mild hypercholesterolaemia. A small but significant increase of Lp(a)
      concentrations was observed with sc-FOS consumption together with a reduction of
      the postprandial insulin response; however, the clinical relevance of these small
      effects is unclear.

PMID- 15158297
TI  - Outcome of percutaneous endoscopic gastrostomy (PEG): comparison of two policies
      in a 4-year experience.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the technique of choice
      for long-term enteral nutrition. Though safe and technically simple, PEG has been
      associated with significant morbidity and mortality. AIM: We compared the outcome
      of strategies applied in two different periods; the original approach of PEG
      insertion during hospitalization (upon request), and PEG insertion 30 days after
      hospital discharge. METHODS: A cohort of 127 patients scheduled for PEG insertion
      from 1.1.1997 to 31.12.2000, was evaluated. In 61 consecutive patients admitted
      from 1.1.1997 to 31.12.1998 the PEG insertion was planned during hospitalization,
      as close to the time of the physician's request (period 1). Sixty-six consecutive
      patients admitted from 1.1.1999 to 31.12.2000 were scheduled for the PEG
      insertion 30 days after discharge (period 2). The 30-day mortality rate was
      calculated from the time of the request. Univariate and multivariate analyses
      were used to find predictive factors for 30-day mortality. RESULTS: There were 61
      patients with a mean age of 78+/-13 in period 1, and 66 patients with a mean age
      of 77.8+/-15.5 in period 2. There was no significant difference between patients
      of the two periods in regard to age, sex, underlying disease, nutritional and
      mental status. Patients received PEG 30 days after hospital discharge had a 40%
      lower 30-day mortality rate than patients who received PEG during hospitalization
      from the time of request for PEG (P=0.01) and a 87.5% lower rate when calculated
      from the time of insertion (P<0.0001). In-hospital PEG insertion, bed-ridden and
      disorientation were found to be independent factors predictive of 30-day
      mortality after PEG insertion (P=0.016,P=0.001, and P=0.0005, respectively).
      CONCLUSION: PEG insertion during hospitalization increases mortality and should
      be avoided. A grace period of 30 days with nasogastric tube feeding before PEG
      insertion may prevent mortality and achieve a long-term enteral nutrition.

PMID- 15158298
TI  - Maldigestion and malabsorption of 13C labelled tripalmitin in gastrostomy-fed
      patients with cystic fibrosis.
AB  - BACKGROUND & AIMS: Some patients with cystic fibrosis continue to have excessive
      losses of stool lipid, despite the use of pancreatic enzyme replacement therapy
      to improve digestion. The aim of this study was to explore the residual capacity
      of the gastrointestinal tract to digest and absorb dietary lipid using stable
      isotopic methodology in ten patients with cystic fibrosis who were gastrostomy
      fed in comparison to eight healthy children. We sought to test the hypothesis
      that a reduction in the availability of dietary lipid may arise from
      malabsorption of the products of digestion, rather than maldigestion alone.
      METHODS: All subjects consumed [1,1,1-(13)C] tripalmitin (10mg/kg body weight)
      with a standardised meal but the patients with cystic fibrosis did not take their
      habitual pancreatic enzymes. Total enrichment of (13)C was measured by isotope
      ratio mass spectrometry in stools collected over 3 days. Maldigestion and
      malabsorption was differentiated by measuring (13)C-label excretion in stool
      triglyceride and fatty acid fractions, respectively. RESULTS: The patients with
      cystic fibrosis had elevated (13)C-label losses in total stools (56.7%, 6.8
      77.9%)(median and range; % administered dose), triglyceride (6.6%, 0-31.2%) and
      fatty acid (16.7%, 3.4-50.3%) fractions compared to healthy children (1.9%, 0
      10.9%, P<0.001; triglyceride: 0.2%, 0-0.6%, p<0.01; fatty acid 0.9%, 0-6.5%,
      P<0.001). CONCLUSIONS: These results highlight differences between gastrostomy
      fed patients with cystic fibrosis to both digest and absorb dietary lipid. There
      is a need to extend these observations and apply this approach to patients both
      with and without pancreatic enzyme replacement therapy.

PMID- 15158299
TI  - Correction of anemia in patients with congestive heart failure increases resting
      energy expenditure.
AB  - BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to
      affect resting energy expenditure (REE). The aim of this study was to evaluate
      the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND
      METHODS: Nine anemic patients with compensated CHF and CRF were studied before
      and after correction of anemia. REE was studied by an open circuit indirect
      calorimeter, body composition by dual-energy-X-ray absorption and total body and
      extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5
      non-anemic CHF patients who did not receive any new treatment served as controls.
      RESULTS: After the correction of their anemia patients tended to increase weight
      (P<0.06), but no significant changes were observed in body composition. Daily
      caloric intake increased significantly (P<0.02). Ejection fraction increased
      (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in
      the normal range before correction but increased significantly afterwards (1402+/
      256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006,
      respectively). CONCLUSION: Correction of anemia in patients with CHF increases
      their REE. This can be related either to improved tissue oxygenation and/or to
      increased caloric intake.

PMID- 15158300
TI  - Body composition and cardiovascular risk factors in pretransplant hemodialysis
      patients.
AB  - BACKGROUND: Obesity, hyperlipemia and cardiovascular complications contribute to
      a significant proportion of morbidity and mortality of renal transplant patients
      and have negative effects on renal survival. Aim of the present study was to
      evaluate the main abnormalities in body composition and the prevalence of some
      cardiovascular risk factors in a population of hemodialyzed (HD) patients
      awaiting renal transplantation. METHODS: We studied 151 HD patients, all included
      in a waiting list for renal transplantation, 97 males and 54 females, with mean
      age 47.4+/-12 years. Patients were divided into three groups according to their
      body mass index (BMI) (kg/m2): 18.5 to 24.9 (normoweight, NW); 25.0 to 29.9
      (overweight, OW); > or =30 (obese, OB). The body composition measurements were
      obtained the day after the mid-week HD session using bioelectrical impedance
      analysis (BIA). RESULTS: We found that 47 patients were NW (31%), while 56 were
      OW (37%), and 48 were OB (32%). BIA-measured body cell mass was (BCM)
      significantly increased in the OW as compared with the NW group (P<0.001), but,
      of note, no significant difference was found in OB group in comparison with the
      OW. Total cholesterol and triglycerides plasma levels were significantly elevated
      in OW and OB patients with respect to NW (P<0.05) and an increased prevalence of
      diabetes was seen in OB patients (NW: 6%, OW: 5%, OB: 12%). CONCLUSIONS: These
      data show that a large proportion of patients awaiting renal transplant are
      overweight or obese and a consistent part of them have other cardiovascular risk
      factors associated. Furthermore, obese HD patients have a BCM lower than
      predicted on the basis of BMI and show an altered metabolic profile. A better
      understanding of the characteristics of patients included in the renal transplant
      waiting list is crucial in order to design prospective studies that aim to define
      the proper risk profile for the selection of patients.

PMID- 15158301
TI  - Selenium concentrations in maternal and umbilical cord blood at 24-42 weeks of
      gestation: basis for optimization of selenium supplementation to premature
      infants.
AB  - BACKGROUND & AIMS: Selenium (Se) deficiency may have deleterious effects on
      premature infants. Umbilical cord (UC) Se concentrations presumably reflect fetal
      Se concentrations and represent reference values that should be achieved in
      premature infants. We aimed to establish reference data of Se serum
      concentrations in parturient women and their neonates across gestation. SUBJECTS
      AND METHODS: Parturient mothers and their newborn infants born after 24-42 weeks
      of gestation were enrolled. Only appropriate for gestational age (GA) singleton
      infants were included. Se serum concentrations were measured by atomic absorption
      spectrometry, in blood samples from parturient mothers and their infants
      (umbilical blood). Demographic, perinatal and labor data were obtained, and their
      correlations with umbilical Se serum concentrations, maternal Se serum
      concentrations, and the maternal-umbilical Se difference were examined. RESULTS:
      UC Se serum concentrations increased as gestation progressed (P<0.01). A
      statistically significant linear relationship was found between UC Se serum
      concentrations and GA (R=0.341, P<0.0001), birth weight (R=0.237, P=0.002), and 5
      min Apgar score (R=0.202, P<0.01). Using multiple regression analysis, only GA
      was significantly associated with UC serum Se concentration (P=0.012). Maternal
      Se serum concentration were stable throughout gestation, and maternal-umbilical
      Se difference was negatively correlated with GA (R=-0.337, P<0.0001) and birth
      weight (R=-0.369, P<0.0001). CONCLUSIONS: UC Se serum concentration increases and
      the maternal-umbilical Se difference declines with gestation progression,
      probably reflecting fetal accretion of Se. With the current Se supplementation in
      premature infants, Se concentrations are lower than those measured in our study.
      We, therefore, suggest a two-fold increase or more in the recommended Se dosage.

PMID- 15158302
TI  - Acute reduction of circulating arginine in mice does not compromise whole body NO
      production.
AB  - The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We
      have now studied the role of acutely reducing circulating arginine on whole body
      NO production in mice. Measurements were performed in 4 groups of mice, treated
      with saline (SAL) or arginase (ASE), and SAL or bacterial endotoxin (LPS). After
      5 h, a 57% reduction in circulating arginine was obtained by intravenous
      injections of arginase (SAL/SAL: 138+/-7; ASE/SAL: 59+/-10 microM, P<0.05).
      Reduced circulating arginine caused a reduction in plasma arginine flux (SAL/SAL:
      82+/-6; ASE/SAL: 63+/-5 nmol/(10 g b.w. min), P<0.05), but did not change whole
      body NO production. LPS treatment caused an increase in NO production (SAL/SAL:
      1.3+/-0.3 SAL/LPS 2.3+/-0.4 nmol/(10 g b.w. min), P<0.05), presumably by NOS-2
      and was unaffected by reducing circulating arginine. Also, intestinal citrulline
      and renal arginine production were not increased in LPS-challenged mice with
      reduced circulating arginine levels. The present study indicates that an acute
      decrease in circulating arginine does not compromise whole body NO production and
      provides evidence against a role for renal arginine production to counteract an
      acute reduction of circulating arginine.

PMID- 15158303
TI  - Glutamine-enriched enteral nutrition increases in vitro interferon-gamma
      production but does not influence the in vivo specific antibody response to KLH
      after severe trauma. A prospective, double blind, randomized clinical study.
AB  - BACKGROUND & AIMS: Severe trauma leads to an immune suppression, characterized by
      a Type 2 T-lymphocyte response, contributing to the susceptibility of infectious
      complications. Plasma concentrations of glutamine (GLN), the preferred fuel for
      immunocompetent cells, severely decrease after trauma. Since administering
      glutamine-enriched enteral nutrition (EN) reduces infectious complications in
      trauma patients, we compared the effect of glutamine-enriched EN with an
      isocaloric, isonitrogenous enteral control (Con) feeding, on the Type 1 and 2 T
      lymphocyte responses. METHODS: Thirty-eight trauma patients (Injury Severity
      Score >20) were sensitized with Keyhole Limpet Hemocyanin (KLH) within 12 h after
      trauma (17 GLN group). Healthy volunteers served as controls (HV, n=17). In vitro
      interferon-gamma (IFN-gamma), IL-4 and IL-10 productions of phytohemagglutinin
      (PHA)-stimulated PBMCs were determined by ELISA technique. KLH-specific IgG, IgM,
      IgA, IgG1, IgG2, IgG3, IgG4 and IgE were measured in serum. RESULTS: Both patient
      groups had a low in vitro (IFN-) production of stimulated PBMCs on d1. On d14,
      the IFN-gamma production increased significantly in the glutamine group as
      compared to the controls. IL-4 production was not different between the groups on
      day 1 (d1). On d14, IL-4 decreased in the control group as compared to the
      glutamine group. KLH-specific antibodies reached comparable levels in both
      patients groups and healthy volunteers at d14. CONCLUSIONS: In conclusion, trauma
      caused a suppressed in vitro cellular immune response presented by a low IFN
      gamma production and depressed the IgG and IgM response to KLH directly after
      trauma. Glutamine increased IFN-gamma production (d14), maintained a normal IL-4
      production, but was not acquired for the development of KLH-specific humoral
      response on d14, in sync suggesting that dietary glutamine supports the
      restoration of the Type-1 T-lymphocyte responsiveness.

PMID- 15158304
TI  - The association of serum lipids, lipoproteins and apolipoproteins with selected
      trace elements and minerals in phenylketonuric patients on diet.
AB  - OBJECTIVE: Classical phenylketonuria (PKU) is an inborn error of metabolism
      characterized by high Phenylalanine (Phe) levels in blood and treated with a
      special low Phe diet which can be defined as "nonatherogenic". Since coronary
      heart disease (CHD) was reported to be a disease of zinc and copper imbalance, we
      aimed indirectly to evaluate the effect of the special diet on the size of LDL
      particles and to investigate whether some minerals and trace elements are
      involved in their lipoprotein metabolism. METHODS: Eighty-six (N=86) PKU patients
      were divided into two groups. Group A (N=44) on a strict diet and group B (N=42)
      who did not adhere to their treatment. Healthy children (N=98) were the controls.
      Serum total cholesterol (t-Chol), triacylglycerol, High-density lipoprotein (HDL)
      and t-Chol in very-low-density lipoprotein (VLDL) and low-density lipoprotein
      (LDL) were measured with enzymatic methods, whereas Apolipoprotein AI (Apo AI),
      Apolipoprotein AII (Apo AII) and Apolipoprotein B (Apo B) were determined by
      nephelometric techniques. LDL/Apo B positively correlated with LDL size.
      Magnesium (Mg), calcium (Ca), copper (Cu) and zinc (Zn) measurements were
      performed by atomic absorption spectrometry. RESULTS: t-Chol, LDL, VLDL, Apo B,
      the ratio t-Chol/HDL, Apo AI/Apo B and LDL/Apo B as well as copper levels and the
      ratio Zn/Cu in group A statistically significantly differed as compared to those
      of group B and Controls. Positive correlations were found between Mg and HDL and
      Apo AI in all the groups whereas the mineral correlated with t-Chol, Apo B and
      the ratio LDL/Apo B only in the group A of patients. Copper negatively correlated
      with triacylglycerol, LDL, and Apo B and positively with t-Chol in group A. Zinc
      showed negative relationships in HDL and Apo A in all the studied groups. The
      ratio Zn/Cu negatively correlated with triacylglycerol and LDL in all the groups
      and positively with the ratios Apo AI/Apo B and LDL/Apo B in group A. CONCLUSION:
      Some of the minerals and trace elements were correlated with the lipids and
      lipoproteins and were also involved in the size of LDL particles in PKU patients
      on strict diet. Larger and less atherogenic LDL particles were associated with a
      high Zn/Cu ratio.

PMID- 15158305
TI  - Nutrition given to critically ill patients during high level/complex care (on
      Italian ICUs).
AB  - BACKGROUND & AIMS: Within a prospective study on costs in 45 Italian intensive
      units we reviewed nutrition support practice given during critical illness.
      METHODS: From June to October 1999, patients with an ICU stay longer than 47 h
      were studied. Nutrition (i.e. fasting, parenteral, enteral and mixed) and calorie
      supply by the enteral route were monitored during the first consecutive days (up
      to seven) of invasive support of organ failure (high-care). RESULTS: 388 patients
      received high-care for at least 1 day, 200 patients had seven consecutive high
      care-days. Some form of nutrition was given in 90.7% of patients, 9.3% were never
      fed (25.8% of the cardiac patients). Parenteral nutrition was given in 13.9% of
      patients (78.9% of the abdominal surgery patients), 39.7% received only enteral
      nutrition, and 36.4% received mixed nutrition. Finally, 77.1% of the patients
      received nutrient by gut. Nutrition was given in 78.5% of 2115 collected days,
      44.1% of the first high-care-days and 93.5% of the 7th days were positive for
      nutrition. Enteral calorie load on the first day was similar for enteral and
      mixed nutrition (range 8-14 kcal/kg), it was higher for exclusive enteral
      nutrition between the 4th and the 7th day (15-19 vs. 11-14 kcal/kg). It differed
      according to diagnosis group. CONCLUSIONS: In Italian ICUs, in complex critically
      ill patients, nutrition is consistently given in critical illness, gut is widely
      used except in abdominal surgery patients.

PMID- 15158306
TI  - Glucose-based total parenteral nutrition does not stimulate glucose uptake by
      humans tumours.
AB  - BACKGROUND: Since glucose represents the preferred fuel for cancer cells, there
      is some debate about the potential stimulation of tumour metabolism induced by a
      glucose-based total parenteral nutrition (TPN) in cancer patients. METHODS: We
      investigated the uptake of [18]2-fluoro-2-deoxy-D-glucose (FDG) through the
      positron emission tomography of the healthy liver and of the tumour in 12
      patients with liver metastases from colorectal cancer. We determined whether FDG
      uptake by the tumour in fasting conditions was affected by the subsequent
      administration of a glucose-based (GTPN) or a lipid-based (LTPN) containing
      glucose 4 mg/kg/min or lipid 2 mg/kg/min, respectively, as non-protein energy
      source. RESULTS: The data showed that FDG uptake by the metastases was 3-3.6
      times higher than by the healthy liver in fasting conditions and it was not
      significantly affected by the subsequent administration of GTPN or LTPN.
      CONCLUSIONS: We speculated that, despite glucose being the preferred fuel for
      cancer cells, its disproportionately high uptake even in fasting conditions makes
      the glucose consumption unable to be modulated by a further supply of glucose or
      lipid.

PMID- 15158308
TI  - Ancel Keys centenary and the definition of healthy diet.

PMID- 15158307
TI  - Pomegranate juice consumption for 3 years by patients with carotid artery
      stenosis reduces common carotid intima-media thickness, blood pressure and LDL
      oxidation.
AB  - Dietary supplementation with polyphenolic antioxidants to animals was shown to be
      associated with inhibition of LDL oxidation and macrophage foam cell formation,
      and attenuation of atherosclerosis development. We investigated the effects of
      pomegranate juice (PJ, which contains potent tannins and anthocyanins)
      consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the
      progression of carotid lesions and changes in oxidative stress and blood
      pressure. Ten patients were supplemented with PJ for 1 year and five of them
      continued for up to 3 years. Blood samples were collected before treatment and
      during PJ consumption. In the control group that did not consume PJ, common
      carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ
      consumption resulted in a significant IMT reduction, by up to 30%, after 1 year.
      The patients' serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas
      serum LDL basal oxidative state and LDL susceptibility to copper ion-induced
      oxidation were both significantly reduced, by 90% and 59%, respectively, after 12
      months of PJ consumption, compared to values obtained before PJ consumption.
      Furthermore, serum levels of antibodies against oxidized LDL were decreased by
      19%, and in parallel serum total antioxidant status (TAS) was increased by 130%
      after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year
      of PJ consumption by 12% [corrected] and was not further reduced along 3 years of
      PJ consumption. For all studied parameters, the maximal effects were observed
      after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had
      no additional beneficial effects on IMT and serum PON1 activity, whereas serum
      lipid peroxidation was further reduced by up to 16% after 3 years of PJ
      consumption. The results of the present study thus suggest that PJ consumption by
      patients with CAS decreases carotid IMT and systolic blood pressure and these
      effects could be related to the potent antioxidant characteristics of PJ
      polyphenols.

PMID- 15158309
TI  - Role of a nutrition support team in reducing the inappropriate use of parenteral
      nutrition.

PMID- 15158311
TI  - [Obstetric medicine: a key-role for the internist].

PMID- 15158312
TI  - [Auto-antibodies to anti-ENA SSA/RO (52 and 60 kDa): an auto-immunity
      laboratory's experience].
AB  - PURPOSE: Anti-SSA/Ro and anti-SSB/La autoantibodies are frequently encountered in
      SLE or SGS where anti-SSA subtypes 52 and 60 kDa seems to be differently found in
      connection with the disease type: anti-SSA/Ro 60 kDa more frequently found in SLE
      and anti-SSA/Ro 52 kDa in SGS. We try to find if it was interesting in
      identifying these specificities for all anti-ENA screening. METHOD: The study
      included 162 patients' sera found anti-SSA 52 and/or anti-SSA 60 and/or anti-SSB
      positive among 1600 screening tests from the different hospital's services. We
      used two assays: first, dotblot (Innolia-Ana Update INGEN) as a screening test
      and second, an Elisa (ENA-LISA BMD) as confirmation. Thirty-eight control sera
      were found negative with dotblot. RESULTS: Only one subtype of anti-SSA (52 or 60
      kD) or anti-SSB was found for 55 sera (44 anti-SSA 52, 10 anti-SSA 60, 1 anti
      SSB) and 107 sera were found positive for two or more (73 anti-SSA 52 + 60 and 34
      anti-SSA 52 or 60 with another anti-ENA). While anti-SSA 60 kDa alone or not was
      always positive with the Elisa test, neither anti-SSA 52 alone was anti-SSA
      Elisa's positive. Diseases associations results show a greater linking of anti
      SSA 60 kDa with SLE, a frequent linking of combined reactivity anti-SSA 52/60 in
      SLE and SGS and a greater spreading of anti-SSA 52 kDa alone among pathological
      groups, showing an autoimmune disease's linking in 68%. Among SGS, 29% had only
      anti-SSA 52 kDa. CONCLUSION: We suggest screening specific tests for identifying
      anti-SSA/Ro 52 kDa reactivity which are missed by routine testing (tests using
      animal's antigens) and could represent an additional serum marker in Connective
      Tissue Diseases.

PMID- 15158313
TI  - [Muscle diseases in an internal medicine department].
AB  - PURPOSE: (1) To describe the causes of muscular symptoms in patients undergoing a
      muscle biopsy in an internal medicine department; (2) to evaluate the diagnostic
      value of electromyography (EMG), CPK level and muscle biopsy. METHODS: A
      retrospective study including 90 patients from June 1995 to March 2001. RESULTS:
      The diagnosis were: inflammatory diseases (n = 35), non-organic (n = 24),
      peripheral neuropathy (n = 8), undetermined organic diseases (n = 7), metabolic
      diseases (n = 5), toxic diseases (n = 4), infectious diseases (n = 4),
      amyloidosis (n = 3). Diagnosis value of EMG, CPK and biopsy for organicity were:
      sensibility: 82%, 47% and 29%; specificity: 46%, 91%, 100%; positive predictive
      value: 78%, 94% and 100%; negative predictive value: 50%, 40% and 36%. Muscle
      biopsy is always normal when CPK and EMG are normal. It allows a diagnosis in one
      out of three cases if EMG and CPK are differing. It is also indicated when CPK
      are normal and EMG is myogenic. CONCLUSION: Numerous diseases account for
      muscular symptoms. The low rate of diagnostic muscle biopsy imposes a
      comprehensive clinical approach of the patient and justify the implication of
      internal medicine physicians in his care. Early intervention of a psychosomatic
      medicine practitioner in the diagnostic procedure should be evaluated to diminish
      the number of non-contributory biopsies.

PMID- 15158314
TI  - [Use of muscular MRI in inflammatory myopathies].
AB  - PURPOSE: Inflammatory myopathies include polymyositis (PM), dermatomyositis (DM)
      and inclusion body myositis (IBM) which differ in terms of clinical, immuno
      histological presentations, evolution and treatment. Diagnosis is based on the
      muscular biopsy but histological distinction between PM and IBM can be difficult;
      biopsies can be insufficient as well as during follow-up to detect active areas
      within the muscle. CURRENT KNOWLEDGE AND KEY POINTS: Muscular MRI is an important
      tool both in the diagnosis and the follow-up of IMM in the following
      circumstances: Distinction between PM and IBM: fatty infiltration and involvement
      of the anterior group of the thighs are characteristic of IBM whereas isolated
      inflammation and involvement of the three thighs or posterior muscle groups are
      characteristic of PM. Biopsy guidance on the inflammatory lesions depicted on the
      STIR sequence either initially or after a non-conclusive biopsy. To
      differentiate, active disease from steroid myopathy. FUTURE PROSPECTS AND
      PROJECTS: Several multicentric trials are in development both in spectro and
      morphologic MRI to study hypoxic phenomenon in early course of IMM and muscular
      volume evaluation both in normal subjects, congenital or acquired myopathies.

PMID- 15158315
TI  - [Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and
      the prognosis of systemic sclerosis].
AB  - PURPOSE: Systemic sclerosis (SSc) like other connective tissue diseases is
      characterized by the occurrence of antinuclear auto-antibodies (ANA). We reviewed
      the diagnostic value and prognostic value of ANA in SSc. CURRENT KNOWLEDGE AND
      KEY POINTS: LeRoy proposed new criteria of limited forms of SSc which take into
      account the immunological profile of the patients. Anticentromere,
      antitopoisomerase I, antifibrillarin, anti-PM-Scl, antifibrillin or anti-RNA
      polymerase I or III are considered as specific anti-autobodies. Whereas
      anticentromere antibodies are more associated with limited SSc and
      antitopoisomerase I with diffuse SSc, other auto-antibodies were associated with
      other organ involvement : anti-RNA-polymerase I or III and renal crisis, anti-U1
      RNP and pulmonary hypertension and pulmonary fibrosis, etc. Patient with
      persistent antitopoisomerase I antibodies have a poor survival, those with
      antitopoisomerase antibodies that disappear with time have a better prognosis.
      FUTURE PROSPECTS AND PROJECTS: A better identification of the patients with SSc,
      an individual biological profile and organ involvement may help better management
      of the disease and better access to clinical trials. The development of new
      immunological tests and their clinical application should help us in that way.

PMID- 15158316
TI  - [Medical practice analysis in internal medicine: a national descriptive study].
AB  - PURPOSE: This descriptive and epidemiological study was conducted in Mars 2002 in
      Internal Medicine in order to (1) participate in elaborating a White Book about
      the speciality, (2) analyse the post-university formation needs of the
      specialists in Internal Medicine. METHODS: A questionnaire was sent to all
      specialists in Internal Medicine listed on the ADELI file (n = 2155). For the
      first three patients seen in consultation and during hospital stay, questioned
      specialists had to mention the age, sex, origin, motive of the visit, nature of
      symptoms, complexity of the problem and the nature of the required abilities.
      They also had to precise the main diagnosis of all patients seen in the same day.
      RESULTS: Three hundred and sixty answers have been received. Three hundred and
      thirty two were exploitable. Five thousand six hundred and eleven main diagnosis
      were listed. Fifteen percent of the questioned specialists did practise in other
      specialities than Internal Medicine. Orphaned diseases were the most common
      pathologies carried out in consultation (17%). Patients seen during their
      hospital stay suffered more frequently from infectious, haematological and
      malignant diseases. In 55% of the cases, patients were seen in second or third
      line after a visit to a general practitioner or another specialist. The abilities
      of the Internal Medicine specialist alone were sufficient in 70% of the cases to
      solve the problem. Complexity of the problem was evaluated by the specialists
      themselves at about 45/100 on an analogical scale. CONCLUSIONS: This study inform
      the medical community about the type of patients treated by the specialists in
      Internal Medicine, precise the exact nature of their professional exercise and
      their real need in medical post-university formation.

PMID- 15158317
TI  - [Isoprostanes: a putative key role in vascular diseases].
AB  - PURPOSE: Isoprostanes are arachidonic acid metabolites produced by a free-radical
      dependent mechanism. CURRENT KNOWLEDGE AND KEY POINTS: The 15-series F2
      isoprostanes and some 15-series E2-isoprostanes mediate vasoconstriction in
      different vascular beds and species. Furthermore, 15-F2t-IsoP induces smooth
      muscle cells mitogenesis and monocyte adhesion to endothelial cells. In clinical
      studies, 15-F2t-IsoP levels are increased in vascular disorders involving
      atherosclerosis, ischemia-reperfusion and inflammation. FUTURE PROSPECTS AND
      PROJECTS: Whether the effects observed in vitro are observed consistently in vivo
      at physiological concentrations and whether these effects contribute to
      pathological states in vivo is still debated.

PMID- 15158318
TI  - [Report of four women with Duchenne or Becker muscular dystrophy].
AB  - INTRODUCTION: Duchenne and Becker muscular dystrophy are X-linked and affect
      mainly males. The authors report four female cases. EXEGESIS: Four patients
      presented muscular deficiency predominant to lower limbs and chronic disease.
      Female distrophinopathy is understandable by three mechanisms: Turner's syndrome,
      translocation X-chromosome with an autosome and skewed X-chromosome inactivation.
      CONCLUSION: Diagnosis of female Duchenne and Becker muscular dystrophy is really
      difficult if there is not male case in family.

PMID- 15158319
TI  - [Paraneoplastic limbic encephalitis].

PMID- 15158320
TI  - [Lactic acidosis occurring after inhaled beta2 agonists during an asthma attack].

PMID- 15158321
TI  - [Antiphospholipid syndrome revealed by portal vein thrombosis in a patient with
      celiac disease].

PMID- 15158322
TI  - [Endocarditis due to Bacteroides fragilis revealed by portal thrombosis: a case
      report].

PMID- 15158323
TI  - [Hyperpigmentation in pernicious anaemia].

PMID- 15158324
TI  - [Drug-induced eruption after treatment of hyperkeratotic crusted scabies with
      ivermectin].

PMID- 15158325
TI  - Hepatocyte transplantation.

PMID- 15158326
TI  - The resistance of the cirrhotic liver: a new target for the treatment of portal
      hypertension. 1985.

PMID- 15158327
TI  - Different expression pattern of hepcidin genes in the liver and pancreas of
      C57BL/6N and DBA/2N mice.
AB  - BACKGROUND/AIMS: Male C57BL/6 and DBA/2 mice differ in their liver iron content.
      The aim of this study was to examine possible differences in the expression of
      hepcidin genes (Hamp and Hamp2) between the two strains. METHODS: Hepatic mRNAs
      were quantified by real-time PCR. RESULTS: Ferroportin1, transferrin receptor 2
      and HAMP mRNA levels displayed no significant strain differences. However, HAMP2
      mRNA levels were higher in DBA/2N mice. In both strains, HAMP2 mRNA content was
      sex-dependent, with higher values in female animals. Both hepatic HAMP and HAMP2
      mRNA levels were elevated by iron overload, but treatment with lipopolysaccharide
      increased only HAMP mRNA. Lipopolysaccharide also elevated the amount of HAMP
      mRNA in the pancreas, while pancreatic HAMP2 mRNA levels were decreased. Sequence
      analysis of hepcidin amplicons from DBA/2N mice predicted an Asn-->Lys
      substitution at position 73 of the HAMP peptide and a Ser-->Phe substitution at
      position 76 of the HAMP2 peptide. CONCLUSIONS: Hepatic Hamp2 expression displays
      considerable strain- and sex-dependent variation. Lipopolysaccharide increases
      expression of Hamp both in the liver and pancreas, but Hamp2 does not respond to
      lipopolysaccharide treatment. The significance of the amino acid substitutions in
      hepcidin peptides in DBA/2N mice is at present unknown.

PMID- 15158328
TI  - Model for end stage liver disease score predicts mortality across a broad
      spectrum of liver disease.
AB  - BACKGROUND/AIMS: The utility of the model for end stage liver disease (MELD)
      score in non-transplant patients, particularly in those with less severe chronic
      liver disease remains uncertain. We studied and compared the predictive abilities
      of the MELD score and the Child-Turcotte-Pugh (CTP) score for intermediate (1
      year) and long-term (5-year) mortality. METHODS: One thousand six hundred and
      eleven patients with chronic liver disease were studied. Observed and predicted
      survival curves were plotted to evaluate the predictive ability of the MELD score
      for survival. Receiver operating characteristic (ROC) curves was used to compare
      the MELD and CTP score. A multivariable model was constructed to examine
      predictors of mortality. RESULTS: The MELD score was a good predictor of 1-year
      mortality in chronic liver disease (c-statistics for all subgroups >/=0.75) and
      of 3- and 6-month mortality in alcoholic hepatitis (c-statistic >/=0.83). The CTP
      score had similar predictive abilities as the MELD. Hepatic encephalopathy was a
      strong independent predictor of death (Hazard ratio-2.8, P<0.0001). CONCLUSIONS:
      The MELD score is a valid prognostic score for intermediate term mortality in a
      heterogeneous population with chronic liver disease although the CTP score is
      equivalent in predicting survival. Inclusion of hepatic encephalopathy adds
      additional prognostic value to the MELD score.

PMID- 15158329
TI  - Linkage disequilibrium between HLA class II region and autoimmune hepatitis in
      pediatric patients.
AB  - BACKGROUND/AIMS: Susceptibility HLA class II alleles associated with autoimmune
      hepatitis (AIH) were only described in case-control studies. METHODS: The
      transmission/disequilibrium test was used in 50 simplex families with AIH, to
      determine if affected offspring received the disease-associated allele more
      frequently than its alternate. HLA-DRB1 and DQB1 allele genotyping and autoimmune
      regulator (AIRE) polymorphisms located in exons 6, 8 and 10 were investigated by
      PCR-based methods. RESULTS: HLA-DRB1*03 allele was significantly transmitted from
      heterozygous parent to affected offspring (81.5%) with type 1 AIH compared to
      random expected frequency (50.0%; P=0.004) or to unaffected offspring (42.8%;
      P=0.03). HLA-DRB1*1301 allele showed an excess transmission to affected children
      (100%) than expected frequency (P<0.0001) or unaffected offspring (P=0.001). The
      transmission of DQB1*201 or DQB1*0603 alleles showed significant deviation in
      patients compared to random frequencies: (84.8%; P<0.0001 for DQB1*0201 or 100%;
      P<0.0001 for DQB1*0603). HLA-DQB1*0201 showed a strong association with type 2
      AIH in children (100.0%, P=0.0005). CONCLUSIONS: HLA-DRB1 gene is the major
      genetic determinant in HLA class II region for children with type 1 AIH. Type 2
      AIH is associated with the HLA-DQB1gene. Finally, AIRE gene abnormality does not
      contribute to the development of isolated AIH.

PMID- 15158330
TI  - Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic
      stellate cells in the early phase of liver regeneration in the rat.
AB  - BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are known to play a role in
      hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC
      activation at various times after 70% partial hepatectomy (PHx) in the rat.
      METHODS: The hepatic microcirculation was studied using intravital fluorescence
      microscopy (IVFM). Desmin and alpha-SMA within liver tissue were detected by
      immunohistochemistry. In isolated parenchymal liver cells (PLCs) and HSCs, double
      immunostaining was used to identify activated HSC. RESULTS: Using IVFM,
      hepatocyte-clusters were often seen in vivo at 3 days after PHx (PHx3). Distance
      between HSC fell from 61.7+/-2.1 microm in controls to 36.1+/-1.4 microm
      (P<0.001) while the HSC/hepatocyte ratio rose (0.71+/-0.01 to 1.08+/-0.03;
      P<0.001). In >80% of in vivo microscopic fields in the PHx3 group, clusters of
      HSCs were observed especially near hepatocyte-clusters. At PHx1 and PHx3, >20% of
      cells in the PLC-fraction were HSCs which adhered to hepatocytes. At PHx3, in
      addition to desmin staining, isolated HSCs were also positive for BrdU and alpha
      SMA, and formed clusters. HSCs in the HSC-fraction were only positive for desmin
      which indicated that adherence to hepatocytes is required for HSC activation.
      CONCLUSIONS: Our data suggest that HSCs are activated by adhering to hepatocytes
      in the early phase of liver regeneration.

PMID- 15158331
TI  - Sulfur-containing amino acids attenuate the development of liver fibrosis in rats
      through down-regulation of stellate cell activation.
AB  - BACKGROUND/AIMS: We tested the pharmacological action of sulfur-containing amino
      acids on the development of liver fibrosis in rats and on the function of
      cultured stellate cells. METHODS: Liver fibrosis was induced in rats by
      thioacetamide administration or by ligating the common bile duct. DNA synthesis
      of cultured stellate cells was evaluated by BrdU incorporation. The expression of
      proteins and phospho-proteins was determined by western blot analysis. mRNA
      expression was evaluated by RT-PCR. RESULTS: Oral administration of l-cysteine or
      l-methionine attenuated the deposition of collagen in liver tissues in the two
      fibrotic models, accompanying a reduction in the expression of smooth muscle
      alpha-actin and platelet-derived growth factor receptor beta and mRNAs of
      collagens, transforming growth factor-betas and tissue inhibitors of matrix
      metalloproteinase. In cultured stellate cells, l-cysteine and l-methionine
      suppressed the DNA synthesis and the expression of growth factor receptors,
      smooth muscle alpha-actin and type I collagen. They hampered the phosphorylation
      of p44/42 MAPK and Akt under platelet-derived growth factor-BB stimulation.
      Stellate cells were found to express methionine adenosyltransferase 2A.
      CONCLUSIONS: l-Cysteine and l-methionine regulate the activation of stellate
      cells. Their oral supply aids the suppression of the progression of liver
      fibrosis.

PMID- 15158332
TI  - Simultaneous abrogation of NOS-2 and COX-2 activities is lethal in partially
      hepatectomised mice.
AB  - BACKGROUND/AIMS: We have investigated the role of the nitric oxide (NO) and
      prostaglandins (PGs), respectively, synthesized by nitric oxide synthase 2 (NOS
      2) and cyclooxygenase-2 (COX-2), in the outcome of liver regeneration after
      partial hepatectomy (PH). METHODS: Liver mass recovery and molecular parameters
      related to cell proliferation and apoptotic death have been determined. RESULTS:
      NOS-2 and COX-2 are normally both expressed in the remnant liver after PH, and
      inhibition of either one delays regeneration. We found, however, that
      simultaneous suppression of the activities of NOS-2 (by gene knockout) and COX-2
      (by pharmacological inhibition) resulted in animal death between 24 and 72 h
      after PH. Analysis of liver mass recovery and molecular parameters related to
      cell proliferation and apoptotic death revealed increased liver-cell apoptosis
      and an insufficient proliferative response. Broad-specificity caspase inhibitors,
      such as z-Val-Ala-Asp.fmk (z-VAD), or administration of NO-donors, rescued
      animals from death, revealing a critical apoptotic bias at this stage of
      proliferation. CONCLUSIONS: These findings demonstrate that simultaneous
      signaling by NO and prostaglandins plays an important role in the mechanism of
      liver regeneration after PH by protecting the remnant tissue from apoptotic
      death.

PMID- 15158333
TI  - Protective effect of a human C5a receptor antagonist against hepatic ischaemia
      reperfusion injury in rats.
AB  - BACKGROUND/AIMS: Complement activation is induced by ischaemia-reperfusion (I/R)
      and the complement factor C5a plays an important role in organ specific I/R
      injuries. This study investigated the efficacy of a small molecule C5a receptor
      (C5aR) antagonist against hepatic I/R injury. METHODS: Total hepatic ischaemia or
      partial hepatic ischaemia were induced in rats, followed by a period of
      reperfusion. The C5aR antagonist, AcF-[OPdChaWR], was administered at 1 mg/kg
      i.v. or 10 mg/kg p.o. or s.c. before induction of ischaemia. Total hepatic I/R
      induced mortality was measured and partial hepatic ischaemia injury was assessed
      by measuring the serum levels of liver enzymes, tissue or serum TNFalpha, liver
      and lung myeloperoxidase activity, the number of infiltrating neutrophils,
      neutrophilia and liver histopathology. RESULTS: C5aR antagonist treatment reduced
      total hepatic I/R-induced mortality. In partial hepatic I/R rats, treatment with
      the C5aR antagonist significantly attenuated the increases in liver enzymes,
      serum and tissue TNFalpha, myeloperoxidase activity, infiltrating neutrophils,
      neutrophilia, and also reduced liver histopathology. CONCLUSIONS: This study
      shows that an orally active, small molecule C5aR antagonist is effective in
      reducing the markers of tissue damage caused by I/R in the rat, suggesting an
      important role for C5a in I/R injuries in the liver.

PMID- 15158334
TI  - Primary cirrhotic hepatocytes resist TGFbeta-induced apoptosis through a ROS
      dependent mechanism.
AB  - BACKGROUND/AIMS: The cirrhotic liver manifests dysregulated hepatocyte growth by
      poor regenerative capacity, formation of regenerative nodules, and malignant
      transformation to hepatocellular carcinoma. The purpose of this study was to
      determine if dysregulated hepatocyte growth occurs through deficient apoptosis.
      METHODS: Hepatocytes were isolated from normal and CCl(4)-treated mice and
      treated with TGFbeta, TNFalpha, and UV-C, known apoptotic agents. RESULTS:
      Cirrhotic hepatocytes were less sensitive to TGFbeta- (45+/-5 vs. 15+/-3%;
      P<0.003), TNFalpha- (59+/-21 vs. 21+/-8%; P=0.02), and UV-C-induced (31+/-4 vs.
      17+/-4%; P<0.03) apoptosis compared to normal hepatocytes. In normal hepatocytes,
      TGFbeta-induced apoptosis occurred through a ROS-, MPT-, and caspase-dependent
      pathway. Cirrhotic hepatocytes lacked caspase activation, had decreased
      procaspase-8 expression, failed to undergo the MPT, and had increased basal ROS
      activity compared to normal hepatocytes. After treatment with trolox, an
      antioxidant that reduced basal ROS activity, cirrhotic hepatocytes underwent
      apoptosis in response to TGFbeta treatment. CONCLUSIONS: These findings suggest
      that increased ROS activity in cirrhotic hepatocytes plays a critical role in
      mediating cirrhotic hepatocyte resistance to apoptosis. Cirrhotic hepatocyte
      resistance to TGFbeta-induced apoptosis is ROS-dependent and is a mechanism of
      dysregulated growth in the chronically inflamed liver.

PMID- 15158335
TI  - The combination of tamoxifen and 9cis retinoic acid exerts overadditive anti
      tumoral efficacy in rat hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Medical treatment for hepatocellular carcinoma (HCC) remains
      elusive. While an acyclic retinoid improved tumor-free survival after hepatoma
      resection, tamoxifen finally proved ineffective. Combination therapy of both
      agents has not been investigated in vitro and in vivo. METHODS: MH7777A hepatoma
      cells were incubated with tamoxifen (TAM) and 9-cis retinoic acid (CRA) alone or
      in combination. Proliferation rate and apoptosis were assessed by BrdU
      incorporation and flow cytometry. In vivo efficacy was studied using the Morris
      hepatoma model in immunocompetent rats. End points were macroscopic tumor growth,
      metastasis and immunohistochemistry for proliferative and apoptotic tumor cells
      (PCNA and TUNEL staining). RESULTS: In vitro, CRA and TAM monotherapy was
      effective only in the highest concentration. Combination therapy significantly
      enhanced apoptosis rate and growth inhibition in hepatoma cells. While in vivo
      monotherapy did not reduce tumor growth or metastasis, their combination reduced
      tumor size after 28 days by 64.5+/-28%. This was paralleled by an increase in
      TUNEL positive and a decrease in PCNA positive cells. CONCLUSIONS: The
      combination of TAM and CRA enhances their anti-tumoral efficacy in vitro as well
      as in vivo, while monotherapy is ineffective. This combination could be a
      promising adjunctive therapy of HCC.

PMID- 15158336
TI  - Mitoinhibitory effects of the tumor promoter 2-acetylaminofluorene in rat liver:
      loss of E2F-1 and E2F-3 expression and cdk 2 kinase activity in late G1.
AB  - BACKGROUND/AIMS: Examine the mitoinhibitory effect of the liver tumor promoter 2
      acetylaminofluorene (2-AAF) in vivo, with focus on the proteins regulating G1-
      and S progression. METHODS: cdk 2 kinase assay to examine histone H1
      phosphorylation. cdk 4 kinase assay to examine whether active cdk 4/cyclin D
      complexes, capable of phosphorylating Rb, are formed. Western blot to monitor
      protein expression. RESULTS: cdk 4 kinase-mediated Rb phosphorylation was
      increased by AAF treatment. Nuclear expression of the transcription factors E2F-1
      and E2F-3 was downregulated, while E2F-4 was decreased. 2-AAF treatment also
      markedly reduced cdk 2 kinase activity/histone H1 phosphorylation during G1/S
      transition. Western blot showed loss of nuclear as well as cytoplasmic cyclin A
      and cyclin B protein after 2-AAF treatment, while the Rb protein level was
      markedly increased during G1. The cell cycle dependent elevation of nuclear p107
      protein, seen in control livers, was not observed in AAF-treated animals.
      CONCLUSIONS: Effects of 2-AAF; Very low cdk 2 kinase activity that could possibly
      block G1/S-transition; increased pRb level together with diminished levels of
      transcription factors E2F-1 and -3, that could be responsible for reducing the
      expression of E2F target genes such as cyclin A and E2F-1.

PMID- 15158337
TI  - Thioacetamide-induced liver regeneration involves the expression of
      cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes.
AB  - BACKGROUND/AIMS: A regeneration process intended to restore organ function
      follows liver hepatotoxicity induced by a necrogenic dose of thioacetamide (TAM).
      METHODS: The expression of genes related to inflammation such as nitric oxide
      synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) has been analyzed in the course
      of the regenerative response, using NOS-2 KO mice or animals treated with
      selective inhibitors of COX-2. RESULTS: All animals lacking both activities
      survived to the hepatotoxic administration. However, animals deficient for NOS-2
      exhibited more severe organ damage in view of the levels of hepatic serum markers
      of function, as well as an attenuated activation of NF-kappaB. The levels of
      C/EBPs were determined as markers of hepatocyte de-differentiation and
      regeneration, and the expression of COX-2 in TAM treated animals was concomitant
      with a decrease in C/EBP-alpha level. Analysis of cyclin D1, E and PCNA
      correlated with hepatocytes entering into the S phase of cell cycle by the effect
      of TAM. CONCLUSIONS: These data indicate that hepatocytes from TAM-treated mice
      express NOS-2 and COX-2 proteins and initiate the regeneration process that
      follows acute liver injury. However, the absence of NO delays hepatocyte
      regeneration, whereas COX-2-inhibition appears to decrease liver damage.

PMID- 15158338
TI  - Evidence for a relation between the viral load and genotype and hepatitis C virus
      specific T cell responses.
AB  - BACKGROUND/AIMS: The reason why patients with hepatitis C virus (HCV) genotype
      non-1 infection respond better to antiviral therapy than patients with genotype 1
      infection is not known. The aim of this study is to explore the relation between
      the viral genotype, viral load, and the endogenous T cell response. METHODS: The
      viral genotype, the viral load, and the endogenous proliferative T cell response
      to the non-structural 3 protein (NS3) was analysed using serum and peripheral
      blood mononuclear cells from 103 patients with chronic HCV infection. RESULTS:
      Among 71 nontreated patients a T cell response was more common among those
      infected by genotype 3, as compared to those infected with genotype 1 (P<0.05).
      Among 32 patients undergoing antiviral therapy, presence of a T cell response was
      more common in genotype non-1 infected patients than in those infected by
      genotype 1 (P<0.01). Presence of a T cell response was related to a more rapid
      viral clearance (P<0,05), a negative HCV RNA test at week 12 (P<0.05), and a
      shorter viral half-life (P<0.05). CONCLUSIONS: The presence of an NS3-specific T
      cell response is related to the viral genotype and to a more rapid clearance of
      HCV RNA during antiviral therapy.

PMID- 15158339
TI  - Much gained by integrating contact tracing and vaccination in the hepatitis B
      antenatal screening program in Amsterdam, 1992-1999.
AB  - BACKGROUND/AIMS: Hepatitis B control in Europe concentrates on antenatal
      screening to reduce vertical transmission. To reduce horizontal transmission and
      the pool of infectious individuals, the Municipal Health Service of Amsterdam
      integrated tracing and immunising of contacts in the antenatal screening program.
      METHODS: An eight year (1992-1999) descriptive study of this public health
      program, where contacts are tested for serological markers of previous infection,
      and vaccination is offered to susceptible contacts. Chronically infected contacts
      are counselled and referred for treatment if justified. RESULTS: For 738 newly
      identified women testing positive for the hepatitis B surface antigen, 1219
      contacts were reported; 1100 (90.4%) contacts participated, 476 (43%) had
      serological markers of previous infection, of whom 119 (25%) were infectious. Of
      603 eligible contacts, 568 (94%) completed the vaccination series. Country of
      origin was an independent predictor of contact participation and compliance with
      completion of the vaccination series. Postvaccination titres for antibodies
      against the surface antigen were below 10 IU/L in 4.5% of contacts under 30, in
      12.2% of those over 30. CONCLUSIONS: Tracing and immunising susceptible contacts
      of women screened as HBsAg-positive, should be an integral component of any
      country's HBV control program.

PMID- 15158340
TI  - Quantitation of hepatitis B lamivudine resistant mutants by real-time
      amplification refractory mutation system PCR.
AB  - BACKGROUND/AIMS: Lamivudine is an antiviral drug that is used to treat hepatitis
      B virus (HBV) infection. Long-term therapy does not completely suppress viral
      replication, and resistant mutants emerge. Resistance is mediated by changes in
      the tyrosine-methionine-apartate-aspartate (YMDD) motif in the catalytic site of
      the HBV polymerase gene. We describe a method to detect and quantify mutant viral
      populations using amplification refractory mutation system (ARMS) PCR. METHODS:
      We developed a real-time ARMS-PCR to detect point mutations in the polymerase
      gene. Using real-time PCR (LightCycler) with a ResonSense probe, PCRs were
      performed using clones of the HBV polymerase gene containing the different YMDD
      mutations. Dilution series of the templates were made and tested against each of
      the primer pairs. This method was applied to quantify mutant virus in patient
      serum samples. RESULTS: As little as 0.01% mutant DNA in 10(5)-10(9) copies wild
      type DNA were detected. The method is more sensitive than amplicon sequencing,
      which is the current method of mutant determination in the YMDD motif.
      CONCLUSIONS: This study demonstrates a rapid, highly sensitive and reproducible
      method of quantifying mutant HBV virus in lamivudine treated patients. It can be
      used to monitor patients before and during lamivudine therapy.

PMID- 15158341
TI  - Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in
      previously untreated patients infected with HCV genotypes 2 or 3.
AB  - BACKGROUND/AIMS: Treatment duration in patients with chronic hepatitis C in the
      era of standard interferon-alpha plus ribavirin was tailored according to
      hepatitis C virus (HCV) genotype: patients infected with HCV-1 were treated for
      48 weeks, patients infected with HCV-2/3 for 24 weeks. The aim of the present
      study was to investigate this schedule for HCV-2/3 infected patients in the era
      of pegylated interferon-alpha plus ribavirin. METHODS: Patients chronically
      infected with HCV-2 (n=42) or HCV-3 (n=182) were treated with peginterferon alfa
      2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800-1400 mg/day based
      on body weight for 24 weeks. RESULTS: The end of treatment (EOT) and sustained
      virologic response (SVR) was higher in patients infected with HCV-2 (100 and 93%,
      respectively) than in patients infected with HCV-3 (93 and 79%, respectively).
      Baseline viremia (P=0.020), treatment duration >16 weeks (P<0.001) and steatosis
      (<5%, P=0.015) were significant independent predictors of SVR. Adverse events
      resulted in discontinuation in 5% and dose reduction in 22% of patients.
      CONCLUSIONS: Treatment for 24 weeks with peginterferon alfa-2b and ribavirin is
      sufficient in HCV 2 or 3 infected patients. The lower SVR in patients infected
      with HCV-3 compared with HCV-2 infected patients may be related to higher levels
      of steatosis in this population.

PMID- 15158342
TI  - Inhibition of hepatitis C virus NS3-mediated cell transformation by recombinant
      intracellular antibodies.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a major worldwide health
      problem, causing chronic hepatitis, liver cirrhosis and primary liver cancer. In
      addition to its role in the viral polyprotein-processing, the viral NS3 serine
      protease has been implicated in interactions with various cell constituents
      resulting in phenotypic changes including malignant transformation. NS3 is
      currently regarded a prime target for anti-viral drugs thus specific inhibitors
      of its activities should be of importance. With the aim of inhibiting NS3
      mediated cell transformation, we used antibody-phage display to isolate NS3
      specific single-chain antibodies (scFv). METHODS: We have isolated and
      characterized eight anti-NS3 scFvs. We investigated the phenotypic changes that
      NS3-expressing cells undergo upon intracellular expression of these antibodies in
      different subcellular compartments (intracellular immunization), assayed by their
      proliferation rate and their ability to grow anchorage independently. The
      intracellular location of NS3 and the scFvs were analyzed by immunofluorescent
      staining using confocal microscopy. RESULTS: Nuclear targeted anti-NS3
      intrabodies shuttle NS3 from the cytosol to the nucleus with concomitant
      inhibition of cell proliferation and loss of the transformed phenotype.
      CONCLUSIONS: Intracellular immunization-based gene therapy strategies may emerge
      as a promising antiviral approach to interfere with the life cycle and
      tumorigenicity of HCV.

PMID- 15158343
TI  - Real-time quantification of hepatitis B virus core-promoter and pre-core mutants
      during hepatitis E antigen seroconversion.
AB  - BACKGROUND/AIMS: Detection of hepatitis B virus (HBV) core-promoter A(1762)T
      G(1764)A and pre-core G(1896)A mutants has relied on qualitative assays. We
      tested the hypothesis that the quantity of A(1762)T-G(1764)A and G(1896)A mutants
      might have clinical impact, by quantifying these mutants before and after HBe
      antigen (HBeAg) seroconversion in 58 patients. METHODS: A real-time quantitative
      polymerase chain reaction (Q-PCR) was developed, using minor groove binder (MGB)
      conjugated TaqMan probes to impart reaction specificity for wildtype/mutant HBV
      populations. RESULTS: Significant quantities (>20%) of core-promoter A(1762)T
      G(1764)A mutant existed in 65% of patients before and after HBeAg seroconversion,
      and were significantly changed (>20% increase/decrease) in 13% of patients after
      seroconversion. Quantity of A(1762)T-G(1764)A mutants was positively correlated
      with alanine aminotransferase (ALT) (P<0.001) and HBV DNA (P<0.001) levels, both
      before and after HBeAg seroconversion. Significant quantities of pre-core
      G(1896)A mutant existed in about 90% of patients before and after HBeAg
      seroconversion, and were changed in 16% of patients after seroconversion.
      Quantity of G(1896)A mutant was negatively correlated with ALT (P=0.044) and HBV
      DNA (P=0.007) levels. CONCLUSIONS: The A(1762)T-G(1764)A and G(1896)A mutants
      existed in a high proportion of patients before and were unaffected after HbeAg
      seroconversion. The quantities of A(1762)T-G(1764)A mutant were positively and
      G(1896)A mutant negatively correlated with liver inflammation and viral
      replication.

PMID- 15158344
TI  - Hepatic iron concentration does not predict response to standard and pegylated
      IFN/ribavirin therapy in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Iron overload is common among patients with chronic hepatitis C
      (CHC). In this study the role of hepatic iron concentration (HIC) and serum iron
      parameters was assessed to determine response to standard and pegylated
      interferon (IFN)/ribavirin combination therapy in patients with CHC. METHODS:
      Liver biopsies were obtained from 169 IFN-naive patients (m=115, f=54, age:
      40.8+/-10.7) with CHC. 140 patients were treated with standard IFN/ribavirin, 29
      patients with pegylated-IFN/ribavirin. Biopsy specimens were evaluated according
      to the DiBisceglie scoring system and iron grading. HIC was determined by atomic
      absorption spectroscopy. Ferritin and transferrin saturation and presence of HFE
      C282Y and H63D gene mutations were determined at baseline. RESULTS: Nonresponders
      to combination therapy had higher serum ferritin levels at baseline (p<0.01).
      There was no difference of HIC, transferrin saturation levels, and the HFE
      mutation status between responders and nonresponders. Logistic regression
      analysis revealed serum ferritin as an independent predictor of response. HIC
      correlated with the DiBisceglie score (r=0.352, p<0.001), iron grading (r=0.352,
      p<0.001) and serum ferritin (r=0.335, P<0.001). CONCLUSIONS: Pretreatment liver
      iron concentration does not predict response to combination therapy in patients
      with CHC. In contrast, high baseline serum ferritin levels are predictors of poor
      response to antiviral therapy.

PMID- 15158345
TI  - The role of hepatic stellate cells in liver regeneration.

PMID- 15158346
TI  - The cirrhotic hepatocyte: navigating between Scylla and Charybdis.

PMID- 15158347
TI  - Interferon-alpha for hepatitis C: antiviral or immunotherapy?

PMID- 15158348
TI  - Optimizing PEG-interferon and ribavirin combination therapy for patients infected
      with HCV-2 or HCV-3: is the puzzle completed?

PMID- 15158349
TI  - Genetic alterations in hepatocellular adenomas: recent findings and new
      challenges.

PMID- 15158350
TI  - Multiple infarcted regenerative nodules in liver cirrhosis after gastric variceal
      bleeding.

PMID- 15158351
TI  - Staging for hepatocellular carcinoma: look for a perfect classification system.

PMID- 15158355
TI  - Bronchobiliary fistula associated with intrahepatic biloma after transcatheter
      arterial chemoembolization for hepatocellular carcinoma.

PMID- 15158353
TI  - No age-related decrease in frequency of heterozygotes for the HFE C282Y
      haemochromatosis mutation.

PMID- 15158356
TI  - Successful outcome of acute sickle cell intrahepatic cholestasis in a patient
      with sickle/beta+ thalassaemia and chronic hepatitis C virus infection.

PMID- 15158357
TI  - Budd Chiari syndrome associated with angiomyolipoma of the liver.

PMID- 15158358
TI  - The answer: angiotensin II. The question: what do inflammation, oxidant stress
      and fibrogenesis have in common?

PMID- 15158359
TI  - Differential effects on cellular iron metabolism of the physiologically relevant
      diatomic effector molecules, NO and CO, that bind iron.
AB  - Both nitrogen monoxide (NO) and carbon monoxide (CO) are biologically relevant
      diatomic effector molecules that mediate a variety of biological functions
      through their avid binding to iron (Fe). Previous studies showed that NO can
      inhibit Fe uptake from transferrin (Tf) and increase Fe mobilisation from cells
      [J. Biol. Chem. 276 (2001) 4724]. We used CO gas, a CO-generating agent
      ([Ru(CO)3Cl2]2), and cells stably transfected with the CO-producing enzyme, haem
      oxygenase 1 (HO1), to assess the effect of CO on Fe metabolism. These results
      were compared to the effects of NO produced by a variety of NO-generating agents,
      including S-nitrosoglutathione (GSNO), spermine-NONOate (SperNO) and S-nitroso-N
      acetylpenicillamine (SNAP). Incubation of cells with CO inhibited 59Fe uptake
      from 59Fe-Tf by cells, and like NO, reduced ATP levels. Hence, the ability of
      both agents to inhibit 59Fe uptake may be partially mediated by inhibition of
      energy-dependent processes. These results showing a CO-mediated decrease in 59Fe
      uptake from 59Fe-Tf using exogenous CO were in agreement with studies
      implementing cells transfected with HO1. Like NO, CO markedly prevented 59Fe
      uptake into ferritin. In comparison to the avid ability of exogenous CO to
      inhibit 59Fe uptake, it had less effect on cellular 59Fe mobilisation.
      Experiments with HO1-transfected cells compared to control cells showed that 59Fe
      mobilisation was slightly enhanced. In contrast to NO, CO did not affect the RNA
      binding activity of the iron regulatory protein 1 that plays an important role in
      Fe homeostasis. Our studies demonstrate that subtle differences in the chemistry
      of NO and CO results in divergence of their ability to affect Fe metabolism.

PMID- 15158360
TI  - Activation of the Interleukin-6 promoter by a dominant negative mutant of c-Jun.
AB  - The human IL-6 promoter contains multiple regulatory elements such as those
      binding transcription factors belonging to the NF-kappaB (-75/-63), C/EBP (-158/
      145 and -87/-76) and AP-1 (-283/-277) families. Herein, we report that ectopic
      expression of c-Jun, C/EBPdelta, and the p65 subunit of NF-kappaB synergistically
      activates an IL-6 promoter construct containing only a TATA box and a kappaB
      binding site. These results suggest that interactions among NF-kappaB, C/EBP, and
      AP-1, which are all activated by the most powerful physiological inducers of the
      IL-6 gene, namely TNF-alpha and IL-1, may be crucial for maximal activation of
      the IL-6 promoter in response to the two cytokines. Furthermore, we show that a
      mutated form of c-Jun lacking the transactivation domain (TAM-67) was a much
      stronger activator of the IL-6 promoter than c-Jun. In combination with p65
      and/or C/EBPdelta, TAM-67 also synergistically activated the IL-6 promoter, while
      it inhibited TNF-alpha induced AP-1 activity directing an AP-1-responsive
      reporter plasmid. Lastly, electrophoretic mobility shift assay (EMSA) results
      strongly suggest the formation of complexes between p65, C/EBPdelta, and/or c-Jun
      or TAM-67 on the kappaB site, supporting the idea that the functional synergism
      is determined by a physical interaction. These data provide new insight into the
      molecular mechanisms regulating the formation of the transcription complex
      responsible for IL-6 promoter activation.

PMID- 15158361
TI  - Activation of extracellular-signal regulated kinase is required for phagocytosis
      by Lymnaea stagnalis haemocytes.
AB  - Haemocytes are the primary defence cells of molluscs. In the present study,
      extracellular-signal regulated kinase (ERK) 1/2-like proteins were identified
      within Lymnaea stagnalis haemocytes, with apparent molecular weights of 44 and 43
      kDa, respectively. Mitogen-activated protein kinase (MAPK) activity assays have
      confirmed that the L. stagnalis ERK possesses kinase activity towards Elk-1.
      Challenge of haemocytes with bacterial lipopolysaccharide (LPS) resulted in a
      transient activation of ERK, and immunocytochemistry revealed that phospho-ERK
      was present in both the perinuclear region and the nucleus following challenge.
      MAPK/ERK kinase (MEK) inhibitors blocked ERK activation confirming that MEK lies
      upstream of ERK in haemocytes. Moreover, phagocytosis assays, using various
      inhibitors, showed that ERK activity was vital for efficient phagocytosis and
      that ERK may be activated by both Ras-dependent and Ras-independent mechanisms.
      Overall, this study has furthered knowledge of ERK signalling in molluscan
      immunity and has shown that the ERK pathway regulates the phagocytic activity of
      molluscan haemocytes.

PMID- 15158362
TI  - Dual role for poly(ADP-ribose)polymerase-1 and -2 and poly(ADP
      ribose)glycohydrolase as DNA-repair and pro-apoptotic factors in rat germinal
      cells exposed to nitric oxide donors.
AB  - We describe the involvement of poly(ADP-ribose)polymerase 1 and 2 (PARP-1 and -2)
      and poly(ADP-ribose)glycohydrolase (PARG) in the response of rat germinal cells
      to the action of the NO donors, 3-morpholino-sydnonimine (SIN-1) and spermine
      nonoate (SNO). Primary spermatocytes and round spermatids showed a differential
      sensitivity to DNA damage induced by acute exposure to SIN-1 and SNO.
      Spermatocytes were able to repair DNA damage caused by the release of NO from SNO
      but neither spermatocytes nor spermatids could recover from the release of NO and
      O2*- from SIN-1. Addition of the PARPs inhibitor, 3-aminobenzamide, and the PARG
      inhibitor, gallotannin (GT), to germ cell cultures impaired DNA repair
      significantly. Consistent with the DNA repair seen in primary spermatocytes, both
      SIN-1 and SNO induced PARPs activation in these cells. In the case of SIN-1,
      there was an immediate but transient response while SNO induced a delayed but
      more sustained increase in PARPs activity. Chronic exposure of spermatocytes to
      SIN-1 and SNO, however, committed the cells to apoptosis, which coincided with
      proteolysis of PARP-1. The data indicate a dual role for PARPs and PARG in
      germinal cells as key proteins in processes that sense and repair DNA damage as
      well as in the commitment to apoptosis following prolonged oxidative stress.

PMID- 15158363
TI  - Agonist-induced regulation and trafficking of kappa opioid receptors.
AB  - Chronic or repeated administration of kappa opioid agonists leads to tolerance to
      the subsequent drug administration. The mechanisms underlying tolerance are
      complex and changes at the receptor level contribute in part to the development
      of tolerance. This review focuses on agonist-induced phosphorylation,
      desensitization, internalization and down-regulation of the kappa opioid
      receptor. In vivo studies on the rat and guinea pig brains are reviewed, followed
      by in vitro investigations on cells and tissues endogenously expressing the kappa
      opioid receptor. The bulk of the article describes the studies performed after
      cloning of the opioid receptors on regulation and trafficking of the kappa opioid
      receptors (KORs) expressed in various cell systems. Topics reviewed and discussed
      include biochemical mechanisms of desensitization, internalization and down
      regulation, differences in the regulation of the rat and the human kappa opioid
      receptors (rKOR and hKOR, respectively) and the structural basis for the species
      variations, differential abilities of agonists in inducing regulation of the
      hKOR, the relationship (or the lack thereof) of KOR internalization to activation
      of p42/p44 mitogen-activated kinase and to adenylyl cyclase superactivation, the
      role of the PDZ domain-containing protein NHERF-1/EBP50 in the trafficking of the
      hKOR and the relationship between receptor phosphorylation and tolerance
      development in mice. There are still questions remained to be answered. Among the
      issues to be resolved are the signals that direct the sorting of internalized
      hKORs to the recycling and degradation pathways, the recycling pathway(s) of the
      internalized hKOR, the molecular bases of differential regulation of the KORs by
      agonists and the occurrence of agonist-induced KOR internalization occur in vivo
      and, if so, its role in tolerance and dependence.

PMID- 15158364
TI  - Intracoronary endothelin-1 infusion combined with systemic isoproterenol
      treatment: antagonistic arrhythmogenic effects.
AB  - Endothelin-1 secretion and sympathetic activation may play important role in
      cardiovascular pathophysiology. In vivo interactions between these systems are
      not defined. We aimed to study the electrophysiological and haemodynamic effects
      of simultaneous intracoronary endothelin-1 and intravenous isoproterenol
      infusions. 18 anaesthetised open chest dogs were studied after AV-ablation. Mean
      arterial blood pressure, coronary blood flow, left ventricular contractility,
      standard electrocardiograms, right and left ventricular epi- and endocardial
      monophasic action potential (MAP) signals were recorded. Intracoronary endothelin
      1 (30 pmol/min) was given to Group ET (n=6), intravenous isoproterenol (0.2
      microg/kg/min) to Group ISO (n=6), both endothelin-1 and isoproterenol to Group
      ET+ISO (n=6) for 30 min. MAP duration increased in all studied regions of Group
      ET, decreased in all studied regions of Group ISO and ET+ISO (control vs. maximal
      changes of left ventricular epicardial MAP 90% duration, Group ET: 296+/-22 vs
      369+/-20 ms, p<0.05, Group ISO: 298+/-18 vs 230+/-27 ms, p<0.01, Group ET+ISO:
      302+/-18 vs 231+/-10 ms, p<0.01). In Group ET, early after depolarisations (3/6),
      polymorphic non-sustained ventricular tachycardias (6/6), and ventricular
      fibrillation (3/6) could be observed. In Group ISO, monomorphic non-sustained
      ventricular tachycardias (5/6) and atrial fibrillation (3/6) appeared. In Group
      ET+ISO, mono- and polymorphic non-sustained ventricular tachycardias occurred
      (5/6), neither ventricular fibrillation nor atrial fibrillation developed. An
      additive effect of endothelin-1 and isoproterenol on left ventricular
      contractility was observed. Isoproterenol treatment showed antagonistic effect
      against endothelin-1 induced MAP duration prolongation, early after
      depolarisation and ventricular fibrillation formation, while endothelin-1 showed
      protective effect against the development of isoproterenol induced atrial
      fibrillation.

PMID- 15158365
TI  - Armepavine oxalate induces cell death on CCRF-CEM leukemia cell line through an
      apoptotic pathway.
AB  - Drug-induced cell death can occur as a result of DNA damage, which in turn may
      lead to the reduction of bcl-2 expression and activation of caspase-3 expression.
      In the present study, we investigated the effect of armepavines and
      atherosperminine on the cell survival rate and expression of bcl-2 and caspase-3
      in CCRF-CEM cells. Our data have revealed that armepavine oxalate reduced the
      survival rate of CCRF-CEM cells in a dose- and time-dependent manner by MTT
      assay. However, no significant effects of armepavine MeI and atherosperminine N
      oxide on the survival rate of the CCRF-CEM cell were observed. Armepavine oxalate
      induced cell death was considered to be apoptotic on the basis of observed
      formation of the DNA ladder and the typical apoptotic morphological change by
      Hoechst 33258 staining. The expression of bcl-2 protein in CCRF-CEM cells treated
      with 30 microM armepavine oxalate was significantly decreased in western blotting
      analysis. In contrast, the expression of active caspase-3 in the cells was
      increased by armepavine oxalate in a dose-dependent manner. These findings
      indicate the involvement of bcl-2 and caspase-3 in the apoptotic process of CCRF
      CEM cells induced by armepavine oxalate. The increased expression of active
      caspase-3 as well as decreased expression of bcl-2 support the assumption the
      armepavine oxalate-treated cells may be capable to complete the entire apoptotic
      process ending in cell fragmentation.

PMID- 15158366
TI  - Peripheral neuronal nitric oxide synthase activity mediates the antinociceptive
      effect of Crotalus durissus terrificus snake venom, a delta- and kappa-opioid
      receptor agonist.
AB  - Previous work has shown that nitric oxide (NO) mediates the antinociceptive
      effect of Crotalus durissus terrificus venom on carrageenin-induced hyperalgesia.
      In the present study the role of constitutive neuronal or of inducible form of
      nitric oxide synthase on venom effect was determined. The rat paw prostaglandin
      E(2) (PGE(2))-induced mechanical hyperalgesia model was used for nociceptive
      evaluation. The venom (200 microg/kg) administered per oz immediately before
      prostaglandin induced antinociception that persisted for 120 h. The
      characterisation of the antinociceptive effect of the venom in this model of
      hyperalgesia showed that kappa and delta-opioid receptors are involved in this
      effect. 7-nitroindazole (7-NI), a neuronal nitric oxide synthase (NOS) inhibitor,
      but not L-N(6)-(1-iminoethyl)lysine (L-NIL), an inhibitor of the inducible form
      of NOS, injected by intraplantar (i.pl.) route, antagonized the antinociceptive
      effect of the venom. The i.pl. administration of 1H-(1,2,4)oxadiazolo[4,3
      a]quinoxaline-1-one (ODQ), a selective guanylate cyclase inhibitor, blocked
      antinociception, whereas Rp-cGMP triethylamine, a cGMP-dependent protein kinase
      inhibitor, partially reversed this effect. These data indicate that peripheral
      kappa- and delta-opioid receptors are involved in the antinociceptive effect of
      Crotalus durissus terrificus on prostaglandin E(2)-induced hyperalgesia.
      Peripheral nitric oxide, generated by neuronal NO synthase, and cGMP/PKc are
      responsible, at least partially, for the molecular mechanisms of venom effect.

PMID- 15158367
TI  - In vivo trafficking of endothelial progenitor cells their possible involvement in
      the tumor neovascularization.
AB  - Circulating endothelial progenitor cell (EPCs) have been reported to contribute
      to vasculogenesis in adult organisms. To investigate the possible recruitment of
      EPCs and organization to form tumor vasculature, we investigated the in vivo real
      time trafficking of EPCs non-invasively by using positron emission tomography
      (PET). A conditionally immortalized endothelial cell line derived from rat bone
      marrow (TR-BME1) was labeled with [2-(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) and
      chased the accumulation in the rat tumor with PET. TR-BME1 cells were accumulated
      in the tumor tissues time-dependently. To investigate that the accumulation of
      the cells is specific or not, rats were previously irradiated with gamma-ray to
      suppress the influence of non-labeled EPCs derived from its bone marrow and used
      for PET analysis. The accumulation of TR-BME1 cells in the tumor was enhanced in
      gamma-ray-irradiated rats compared with that of non-irradiated ones, suggesting
      that TR-BME1 cells accumulated in the tumor specifically like as EPCs. Then the
      involvement of matrix metalloproteinases (MMPs) in EPC recruitment was examined.
      An inhibitor of MMP, MMI270, which suppressed invasion and tube formation
      abilities of TR-BME1 cells, only slightly suppressed the accumulation of TR-BME1
      cells in the tumor of rats. These results suggest that EPCs are recruited in the
      tumor tissues for formation of tumor vasculature, and demonstrate the usefulness
      of TR-BME1 cells for studies on EPC related phenomena.

PMID- 15158368
TI  - Hyperphosphorylation of rat liver proteasome subunits: the effects of ethanol and
      okadaic acid are compared.
AB  - In experimental alcoholic liver disease, protein degradation by the ATP-ubiquitin
      proteasome pathway is inhibited. Failure of the proteasome to eliminate
      cytoplasmic proteins leads to the accumulation of oxidized and otherwise modified
      proteins. One possible explanation for the inhibition of the proteasome is
      hyperphosphorylation of proteasome subunits. To examine this possibility, the 26S
      proteasomes from the liver of rats fed ethanol and a pair-fed control were
      studied by isolating the proteasomes in a purified fraction. The effect of
      ethanol on the phosphorylation of proteasomal subunits was compared with the
      hyperphosphorylation of the proteasomes caused by okadaic acid given to rats in
      vivo. Ethanol ingestion caused an inhibition of the chymotrypsin-like activity of
      the purified proteasome. The 2D electrophoresis and Western blot analysis of the
      purified 20S and 26S proteasomes from the ethanol-fed rats indicated that
      hyperphosphorylation of proteasomal subunits had occured. The proteasomal alpha
      type subunits C9/alpha3 and C8/alpha7 were hyperphosphorylated compared to the
      controls. Chymotrypsin-like activity was also inhibited by okadaic acid treatment
      similar to ethanol feeding. The 26S proteasome fraction examined by isoelectric
      focusing gel revealed many hyperphosphorylated bands in the proteasomes from the
      okadaic acid treated and the ethanol fed rat livers compared with the controls.
      In conclusion hyperphosphorylation of the proteasome subunits occurs in the
      ethanol treated proteasomal subunits which could be one mechanism of the
      inhibition of the 26S proteasome caused by ethanol feeding.

PMID- 15158369
TI  - Suppression by 17beta-estradiol of monocyte adhesion to vascular endothelial
      cells is mediated by estrogen receptors.
AB  - Several observational studies have shown that estrogen replacement therapy
      decreases cardiovascular mortality and morbidity in postmenopausal women.
      However, The Women's Health Initiative (WHI) study has found that women receiving
      estrogen plus progestin had a significantly higher risk of breast cancer,
      coronary heart disease, stroke, and pulmonary embolus. In the present study, we
      examined whether estrogen prevents mechanisms that relate to plaque formation by
      inhibiting monocyte adhesion to endothelial cells. ECV304 cells, an endothelial
      cell line that normally expresses minimal estrogen receptor (ER)alpha, were
      transfected with an ERalpha expression plasmid. Treatment with tumor necrosis
      factor (TNF)-alpha increased expression of vascular cell adhesion molecule (VCAM)
      1 mRNA, activation of nuclear factor-kappaB (NF-kappaB), and U937 cell adhesion
      in ECV304 cells. These effects of TNF-alpha were not significantly inhibited by
      pretreatment of native ECV304 cells with 17beta-estradiol (E(2)). In ECV304 cells
      overexpressing ERalpha, E(2) significantly inhibited the effects of TNF-alpha on
      NF-kappaB activation, VCAM-1 expression, and U937 cell adhesion. These findings
      suggest E(2) suppresses inflammatory cell adhesion to vascular endothelial cells
      that possess functional estrogen receptors. The mechanism of suppression may
      involve inhibition of NF-kappaB-mediated up-regulation of VCAM-1 expression
      induced by atherogenic stimuli. E(2) may prevent plaque formation, as first stage
      of atheroscrelosis through inhibiting adhesion monocytes to endothelial cell.
      Actions of estrogen replacement therapy can be assessed in terms of densities of
      functional ERalpha.

PMID- 15158370
TI  - Cigarette smoke concentrate increases 8-epi-PGF2alpha and TGFbeta1 secretion in
      rat mesangial cells.
AB  - Epidemiological studies have shown that cigarette smoke, an oxidant agent, is a
      risk factor for the development of diabetic nephropathy (DN), in which
      pathogenesis transforming growth factor beta(1) (TGFbeta(1)) plays a key role. In
      our experimental model we exposed mesangial cell cultures to cigarette smoke
      concentrate (CSC) to study the effect of smoking on the pathogenesis of DN. Thus,
      we analyzed the effect of CSC on TGFbeta(1) and lipid peroxidation (8-epi
      PGF(2alpha)) in rat mesangial cells. Furthermore, since the protein kinase C
      (PKC) pathway appears to be a key factor for the enhanced production of
      TGFbeta(1), we also analyzed the effect of the selective PKCbeta inhibitor
      LY379196 on TGFbeta(1) response to CSC. CSC induced an increase of both
      TGFbeta(1) and 8-epi-PGF(2) compared to basal conditions (5 mM glucose). The CSC
      induced increase in TGFbeta(1) secretion was significantly suppressed by
      LY379196. These data suggest that smoking could increase TGFbeta(1) production,
      probably due to oxidative stress and PKCbeta activation. This finding supports
      the concept that smoking is a risk factor for DN development.

PMID- 15158371
TI  - Changes in G1-phase populations in human glioblastoma and neuroblastoma cell
      lines influence p66/Be neutron-induced micronucleus yield.
AB  - Some photon resistant tumours are sensitive to neutrons but no predictive methods
      exist which could identify such tumours. In a recent study addressing this
      clinically important issue, we demonstrated that relative biologic effectiveness
      (RBE) values for p(66)/Be neutrons estimated from micronucleus (MN) data
      correlate positively with RBE values obtained from conventional clonogenic
      survival data. However, not all photon-resistant cell lines showed high RBE
      values when the MN endpoint was used. Now, we examine how the functional status
      of the p53 tumour suppressor gene and radiation-induced changes in cell cycle
      phase populations may contribute to this discrepancy. No significant association
      was established between p53 status and MN yield for both photon and neutron
      irradiation. The data demonstrated that neutron-, but not photon-, induced MN
      yield is dependent on the intrinsic ability of cells to activate a G1-phase
      arrest. In cell lines of comparable photon sensitivity, those showing more
      extensive depletion of the G1 population express significantly more micronuclei
      per unit dose of neutrons. These results suggest that differences in cell cycle
      kinetics, and not the p53 status, may constitute an important factor in damage
      induction by high linear energy transfer (LET) irradiation and need to be
      considered when radiation toxicity in clinical radiobiology or radiation
      protection is assessed using damage endpoints.

PMID- 15158373
TI  - Thermodynamical model and prediction of gas/solid adsorption isotherms.
AB  - A thermodynamic model of gas/solid adsorption has been constructed from two
      elements. One of those is the original Gibbs equation. The second is functions
      psi(theta) or psi(P) calculable from measured isotherms. The model provides the
      possibility of calculating the relative change in free energy of the surface, and
      based on the model, implicit isotherm equations of general validity and in
      integral form can be derived. The prediction of isotherms can be made based on
      characteristic adsorption functions (CAFs). The CAFs concentrate in one function
      all measured isotherms having the same change in relative free energy of the
      surface. From CAFs any isotherm can be predicted if one measured point is known
      or one required datum of the isotherm can be defined. The maximum average
      deviation between the measured adsorbed amounts and those calculated from the
      CAFs is +/-10%. The CAFs are very sensitive to the internal structure of
      adsorbents (micro-, meso-, and macropores and nanostructures). It is the goal of
      future investigations to determine the exact connections related to the CAFs and
      to the structure of adsorbents.

PMID- 15158372
TI  - Cannabidiol increases Fos expression in the nucleus accumbens but not in the
      dorsal striatum.
AB  - Preclinical and clinical studies suggest that cannabidiol (CBD), a major
      component of Cannabis sativa, could produce antipsychotic effects without causing
      extra-pyramidal side-effects. In the present paper we employed the detection of
      Fos protein to investigate neuronal activation in the dorsal striatum and nucleus
      accumbens of male Wistar rats after systemic administration of CBD (120 mg/kg),
      haloperidol (1 mg/kg) or clozapine (20 mg/kg). Only haloperidol was able to
      increase the number of Fos immunoreactive neurons (FIr) in the dorsal striatum
      (vehicle: 0.07 +/- 0.07/0.1 mm(2), haloperidol: 28.3 +/- 8.9/0.1 mm(2), p <
      0.01). In contrast, both haloperidol and CBD significantly increased FIr in the
      nucleus accumbens (Vehicle: 0 +/- 0/0.1 mm(2), haloperidol: 7.2 +/- 2.7/0.1
      mm(2), CBD: 4.0 +/- 1.9/0.1 mm(2), p < 0.05). Clozapine also produced a barely
      significant increase in FIr (3.0 +/- 1.7/0.1 mm(2), p = 0.062). These results
      show that CBD is able to induce FIr in a limbic- but not in a motor-related area.

PMID- 15158374
TI  - Molecular properties and intermolecular forces--factors balancing the effect of
      carbon surface chemistry in adsorption of organics from dilute aqueous solutions.
AB  - Presented paper recapitulates the results of 6 years' study concerning the effect
      of carbon surface chemical composition on adsorption of paracetamol, phenol,
      acetanilide, and aniline from dilute aqueous solutions on carbons. Adsorption
      desorption isotherms, enthalpy, and kinetics of adsorption data are shown for the
      measurements performed at three temperatures (300, 310, and 320 K) at two pH
      levels (1.5 and 7) on commercial activated carbons. The data were obtained for
      four carbons: the initial carbon D43/1 and forms modified by applying
      concentrated HNO3, fuming H2SO4, and gaseous NH3. The modification procedures do
      not change the porosity in a drastic way, but lead to drastic changes of the
      composition of carbon surface layer. By applying MOPAC (a general-purpose
      semiempirical molecular orbital package), the physicochemical constants
      characterizing the molecules of adsorbates are calculated, including the
      distribution of the Mulliken charges, the dipole moments and ionization
      potentials, and the energies of interaction with the unique positive and negative
      charges. They are correlated with the parameters characterizing the adsorption
      (and kinetics) process of studied molecules on the mentioned above carbons. The
      mechanisms proposed in the literature for the description of adsorption from
      dilute aqueous solutions are verified, and a general mechanism of adsorption is
      proposed.

PMID- 15158375
TI  - A simplified approach for evaluation of the polarity parameters for polymer using
      the K coefficient of the Mark-Houwink-Sakurada equation.
AB  - Since two solvent polarity parameters, e.g., the Et(30) defined by Reichardt and
      the pi* defined by Kamlet and Taft, respectively, plotted with the K coefficient
      of the Mark-Houwink-Sakurada equation, presented good linear fits, this paper
      suggests applying the extrapolating method in the same way as the Zisman plot to
      obtain similar polarity parameters for polymers. In order to verify those
      obtained polarity parameter values for various polymers, literature-reported
      polarity values determined using other techniques are referenced and indicate
      that this paper introduced a simplified approach that can be applied to evaluate
      the polarity parameters for polymers. In this paper, since we observe that
      various polymers are of interest to present absolutely different slope
      tendencies, e.g., positive and negative, it is also suggested that polarity
      properties of polymers may be reinterpreted.

PMID- 15158376
TI  - Adsorption of fluoride ions onto carbonaceous materials.
AB  - The characteristics of fluoride ion adsorption onto carbonaceous materials were
      derived as adsorption isotherms at different temperatures and in different pH
      solutions. The fluoride ion was adsorbed into pores in carbonaceous materials
      produced from wood; the larger the specific surface area, the more fluoride ions
      adsorbed. Bone char was the most effective adsorbent. The composition of bone
      char includes calcium phosphate, calcium carbonate, and so on. This suggests that
      the phosphate ion in bone char was exchanged with a fluoride ion. Moreover, the
      mechanism of fluoride ion adsorption onto bone char is clearly chemical in nature
      because the amount of fluoride ion adsorbed onto bone char increased with
      increasing temperature and decreasing pH. The amount of fluoride ion adsorbed
      onto bone char was also shown to depend on the concentration of sodium chloride
      in solution because of the "salting-out" effect. The adsorption of fluoride ion
      onto bone char is endothermic. Bone char can be utilized to remove fluoride ions
      from drinking water.

PMID- 15158377
TI  - Study on adsorption kinetic of aromatic hydrocarbons onto activated carbon in
      gaseous flow method.
AB  - The adsorption behavior of benzene, toluene, o-xylene, m-xylene, and p-xylene
      onto activated carbon was investigated using the flow method. The removal
      efficiency of aromatic hydrocarbons in the gaseous phase was estimated based on
      the adsorption kinetic constants and the saturated amount of aromatic
      hydrocarbons adsorbed on the activated carbon. The saturated amount of benzene
      and toluene adsorbed was greater than that of xylene adsorbed because the
      molecular sizes of benzene and toluene are smaller than that of xylene. The
      adsorption kinetic constant increased in the order of xylene, toluene, and
      benzene. Those of the three xylene isomers were similar. These results indicated
      that the adsorption rate of benzene by the activated carbon was the fastest and
      the kinetic constant depended upon the different between the boiling point and
      the melting point and the molecular size of the aromatic hydrocarbons.

PMID- 15158378
TI  - Adsorption of tetraalkylammonium ions on microporous and mesoporous activated
      carbons prepared from vinylidene chloride copolymer.
AB  - The adsorption of tetraalkylammonium ions on microporous (AC-micro) and
      mesoporous (AC-meso) activated carbons prepared from vinylidene chloride
      copolymer was investigated. The adsorbed amounts on AC-micro decreased in the
      order of tetraethyl-, tetrapropyl-, hexadecyltrimetyl-, and tetrahexylammonium
      bromide. Consequently it is suggested that the pore size of the activated carbon
      plays an important role in the adsorption. The adsorbed amounts on AC-meso
      increased with increasing alkyl chain length. In the case of mesoporous activated
      carbon, hydrophobic interaction between tetraalkylammonium ions and the surface
      of activated carbons contributes to in the adsorption.

PMID- 15158379
TI  - Anomalous adsorption behavior observed during the characterization of a
      polystyrene film prepared on a mesoporous material.
AB  - Discrepancies in the results obtained during the adsorption of nitrogen, argon,
      and water on two mesoporous samples are compared and contrasted. A silica-based
      mesoporous oxide and the same sample coated with a film of polystyrene were
      chosen with respect to their different surface chemistries. The nitrogen BET
      surface is overestimated on the pure silica sample and underestimated for the
      polymer-coated sample. These differences can be related to the specific
      interaction (strong or weak) of nitrogen with these surfaces. Water has
      difficulty in wetting either surface. Moreover, in the case of the polymer-coated
      material, water is unable to fill the mesopores via capillary condensation.

PMID- 15158380
TI  - Equilibrium sorption of heavy metals and phosphate from single- and binary
      sorbate solutions on goethite.
AB  - The amounts of Cu(II), Zn(II), and phosphate sorbed from single- and binary
      sorbate systems on goethite (alpha-FeOOH) were measured. Experiments were carried
      out as a function of equilibrium pH (2-7), sorbate concentration (0.21-1.57 mM),
      and temperature (15-35 degrees C). The aqueous phase contained 0.1 M NaNO3 to
      maintain ionic strength constant. A convenient method was used to obtain sorption
      isotherms of single Cu(II), Zn(II), and phosphate at a fixed equilibrium pH,
      which could be well described by the Langmuir equation. Thermodynamic parameters
      for the sorption of single Cu(II) and phosphate including the free energies,
      isosteric enthalpies, and entropies were determined. In contrast to the single
      sorbate systems, the sorption of metals was inhibited in the binary Cu(II)-Zn(II)
      system, whereas the sorption of both sorbates was enhanced in the binary Cu(II)
      phosphate system under the conditions studied. The validity of the Langmuir
      competitive model for the prediction of the sorption isotherms in a binary Cu(II)
      Zn(II) system was also discussed.

PMID- 15158381
TI  - Adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II), and As(V) on
      bacterially produced metal sulfides.
AB  - The adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II) and As(V) onto
      bacterially produced metal sulfide (BPMS) material was investigated using a batch
      equilibrium method. It was found that the sulfide material had adsorptive
      properties comparable with those of other adsorbents with respect to the specific
      uptake of a range of metals and, the levels to which dissolved metal
      concentrations in solution can be reduced. The percentage of adsorption increased
      with increasing pH and adsorbent dose, but decreased with increasing initial
      dissolved metal concentration. The pH of the solution was the most important
      parameter controlling adsorption of Cd(II), Cu(II), Fe(II), Ni(II), Pb(II),
      Zn(II), and As(V) by BPMS. The adsorption data were successfully modeled using
      the Langmuir adsorption isotherm. Desorption experiments showed that the
      reversibility of adsorption was low, suggesting high-affinity adsorption governed
      by chemisorption. The mechanism of adsorption for the divalent metals was thought
      to be the formation of strong, inner-sphere complexes involving surface hydroxyl
      groups. However, the mechanism for the adsorption of As(V) by BPMS appears to be
      distinct from that of surface hydroxyl exchange. These results have important
      implications to the management of metal sulfide sludge produced by bacterial
      sulfate reduction.

PMID- 15158382
TI  - Adsorption of acid dyes from aqueous solution on activated bleaching earth.
AB  - In the present study, activated bleaching earth was used as clay adsorbent for an
      investigation of the adsorbability and adsorption kinetics of acid dyes (i.e.,
      acid orange 51, acid blue 9, and acid orange 10) with three different molecular
      sizes from aqueous solution at 25 degrees C in a batch adsorber. The rate of
      adsorption has been investigated under the most important process parameters
      (i.e., initial dye concentration). A simple pseudo-second-order model has been
      tested to predict the adsorption rate constant, equilibrium adsorbate
      concentration, and equilibrium adsorption capacity by the fittings of the
      experimental data. The results showed that the adsorbability of the acid acids by
      activated bleaching earth follows the order: acid orange 51 > acid blue 9 > acid
      orange 10, parallel to the molecular weights and molecular sizes of the acid
      dyes. The adsorption removals (below 3%) of acid blue 9 and acid orange 10 onto
      the clay adsorbent are far lower than that (approximately 24%) of acid orange 51.
      Further, the adsorption kinetic of acid orange 51 can be well described by the
      pseudo-second-order reaction model. Based on the isotherm data obtained from the
      fittings of the adsorption kinetics, the Langmuir model appears to fit the
      adsorption better than the Freundlich model. The external coefficients of mass
      transfer of the acid orange 51 molecule across the boundary layer of adsorbent
      particle have also been estimated at the order of 10(-4)-10(-5) cm s(-1) based on
      the film-pore model and pseudo-second-order reaction model.

PMID- 15158383
TI  - Alteration of the surface charge of aluminum goethites by a sulfonic acid buffer.
AB  - Four samples of synthetic low-substitution Al-goethites (mol% Al<10) were
      incubated with 10 mM NaClO4 and 5 mM MES buffer (MES buffer (2-[N
      morpholino]ethanesulfonic acid) at pH 5. It was found that MES buffer, although
      commonly used to control pH, profoundly affected the results of our
      electrophoretic mobility measurements. The presence of MES buffer caused a large
      decrease in EM values for unsubstituted goethite, from 5.7 +/- 0.7 to 1.8 +/- 0.4
      m2 v(-1) s(-1), while increases in Al substitution in goethite led to a
      progressive increase in EM values. The charge reversal following addition of MES
      buffer to suspension containing Al-goethites was explained by specific sorption
      that, at pH 5, is thought to occur via cation surface complexation because of (i)
      sulfonate induced-dipole or (ii) N and O lone-pair dipole-dipole interactions
      with structural Fe.

PMID- 15158384
TI  - Cadmium complexation by bacteriogenic iron oxides from a subterranean
      environment.
AB  - This study quantifies the metal sorption characteristics of subterranean
      bacteriogenic iron oxides (BIOS) and their organic phases (intermixed intact and
      fragmented bacteria). A Cd2+ ion-selective electrode was used to generate high
      resolution metal sorption data as a function of increasing pH. A multisite
      Langmuir model, along with a linear programming regression method (LPM), was
      applied to fit experimental data. This approach found two discrete Cd2+ binding
      sites for the BIOS with average -log10 equilibrium constants (pK(S,j)) of 1.06 +/
      0.19 and 2.24 +/- 0.28. Three discrete sites were obtained for the bacterial
      fraction, with pK(S,j) values of -0.05 +/- 0.12, 1.18 +/- 0.02, and 3.81 +/-
      0.16. This indicated that the BIOS surface had a lower affinity for Cd2+ than
      that of the bacteria. pK(S,j) values for the BIOS were similar to those reported
      for pure iron oxide phases, while the organic fraction pK(S,j) spectrum was
      consistent with previous spectra for intact bacteria. Individual binding site
      densities of 0.04 +/- 0.01 and 0.05 +/- 0.02 and 0.29 +/- 0.05, 0.11 +/- 0.01,
      and 0.09 +/- 0.02 micromol/mg of BIOS corresponded to the iron oxide mixture and
      bacteria fraction, respectively. These values indicated high concentrations of
      strong affinity Cd2+ complexing groups on the bacterial surface. Comparison of
      total site densities of 0.08 +/- 0.02 and 0.48 +/- 0.06 micromol/mg of BIOS for
      the mixture and the bacterial phase, respectively, suggested a nonadditive
      character for the BIOS surface reactivity. This was emphasized by a higher
      affinity for Cd2+, as well as an increase in total site concentration observed
      for the bacterial phase. LPM was able to distinguish between the BIOS mixture and
      its organic fraction Cd2+ complexation characteristics. This approach is
      therefore a useful tool for the study of natural sorbent materials controlling
      metal partitioning in contaminated and pristine environments.

PMID- 15158386
TI  - Ionizable polyelectrolyte brushes: brush height and electrosteric interaction.
AB  - Semi-analytical scaling theory is used to describe quenched and annealed (weakly
      charged, ionizable, charge-regulating) polyelectrolyte brushes in electrolyte
      solutions of arbitrary salt concentration. An Alexander-De Gennes box model with
      homogeneous distribution of polymer segments and the free ends located at the
      edge of the brush is assumed, as is local electroneutrality in the brush. For
      annealed polyelectrolyte and in the low-salt regime, the theory predicts that for
      sufficiently dense brushes, the salt concentration has a small influence on brush
      height, while the brush expands with increasing grafting density, in agreement
      with experiment. Expressions are presented for the interaction free energy of
      compressed ionizable and quenched polyelectrolyte brushes (proportional to the
      force between particles or curved surfaces). In all cases, the required
      prefactors are explicitly stated. The theory is compared directly with published
      experiments on the influence of salt concentration, pH, and grafting density on
      the thickness and interaction force of polystyrene sulfonate (quenched) and
      poly(meth)acrylic acid (annealed) brushes. In general, trends are well reproduced
      but significant deviations remain.

PMID- 15158385
TI  - Prediction of multicomponent liquid adsorption using excess quantities I.
      Statistical thermodynamic derivation of the basic equation of excess formalism.
AB  - The utilization of excess quantities as the basis of a thermodynamic approach can
      simplify the prediction of multicomponent liquid adsorption from binary data.
      From statistical thermodynamics, the fundamental equation is derived for the
      prediction of ternary or higher order data from adsorption data for the
      constituent binary mixtures. An additive expression is obtained for the double
      Gibbs free excess energies, valid for adsorption on liquid mixture/air interfaces
      as well as liquid mixture/solid interfaces.

PMID- 15158387
TI  - An interpretation of amphoteric gel hardness variation through potential and
      hardness measurement.
AB  - The hardness variation of amphoteric gel according to the surrounding solution
      conditions is quite unique. It hardens and softens reversibly regardless of its
      molecular network density. But this has been understood merely qualitatively. For
      the purpose of elucidation of the details of its behavior, we performed
      quantitative potential and hardness measurements on it. We observed the constant
      potential of amphoteric gels, approximately -60 mV, regardless of their swelling
      ratio and hardness. Such observations can be interpreted as the maintenance of
      the constant charge density of *COO- for any amphoteric gel, and they are further
      interpreted as intermolecular salt-linkage formation/disruption dominating the
      hardness of amphoteric gels.

PMID- 15158388
TI  - Extension of Colacicco's experiment supporting the adsorption theory.
AB  - The pervasive concept of the cause of the potential occurring across a
      semipermeable membrane intervening between two ionic solutions is called the
      membrane theory; hence, this potential is called the membrane potential. Although
      almost nobody has doubted its validity, research results defying it have been
      continuously reported by a small number of researchers. They have claimed that
      the cause the potential lies in the adsorption of ions onto adsorption sites,
      which is the adsorption theory. One such research report by G. Colacicco (Nature
      207 (1965) 936) was employed for our experimental work reported in this paper in
      order to examine the validity of the membrane theory and the adsorption theory.
      The results we obtained are in conflict with the membrane theory but appear to be
      in full agreement with the long dismissed adsorption theory. This paper urges the
      reexamination of the membrane theory and the reconsideration of the adsorption
      theory from a nonbiased standpoint.

PMID- 15158389
TI  - Surface density as a significant parameter for the enzymatic activity of two
      forms of alkaline phosphatase immobilized on phospholipid Langmuir-Blodgett
      films.
AB  - Rat osseous plate alkaline phosphatase, a glycosylphosphatidylinositol (GPI)
      anchored phosphomonohydrolase, was immobilized on Langmuir-Blodgett (LB) films.
      Enzyme solubilization either with polyoxyethylene-9-lauryl ether or with a
      glycosylphosphatidylinositol-specific phospholipase C resulted in a GPI-anchor
      containing and a GPI-anchor-depleted form, respectively. Both forms were adsorbed
      on dimyristoylphosphatidic acid LB films and restricted to the outermost layer.
      The surface density and enzyme activity were determined using a quartz crystal
      microbalance and p-nitrophenylphosphatase activity, respectively. The detergent
      solubilized form was co-spread with dimyristoylphosphatidic acid on the air/water
      interface and transferred to solid supports, providing an enzyme maximum surface
      density of 530 ng/cm2. Maximal phosphohydrolytic activity, corresponding to 43%
      of that observed in homogeneous medium, was obtained at a surface density of 179
      ng/cm2. The phospholipase C-solubilized form was adsorbed directly from solution,
      reaching a maximum surface density of 1541 ng/cm2, although the
      phosphomonohydrolase activity was 10 times lower than that obtained for the
      anchor-containing form. The combined analysis of surface density and enzymatic
      activity suggests that the alignment of the protein molecules on the LB lipid
      films induced by the glycosylphosphatidylinositol anchor facilitates the access
      of the substrate to the active site. This access is hampered by increasing enzyme
      surface densities and depends on a specific orientation of the adsorbed enzyme.

PMID- 15158390
TI  - Sorption of lead, copper, cadmium, zinc, and nickel by marine algal biomass:
      characterization of biosorptive capacity and investigation of mechanisms.
AB  - The marine algae Sargassum sp., Padina sp., Ulva sp., and Gracillaria sp.,
      harvested locally, were investigated for their biosorption performance in the
      removal of lead, copper, cadmium, zinc, and nickel from dilute aqueous solutions.
      It was found that the biosorption capacities were significantly affected by
      solution pH, with higher pH favoring higher metal-ion removal. Kinetic and
      isotherm experiments were carried out at the optimal pH: at pH 5.0 for lead and
      copper, and at pH 5.5 for cadmium, zinc, and nickel. The metal removal rates were
      rapid, with 90% of the total adsorption taking place within 60 min. Sargassum sp.
      and Padina sp. showed the highest potential for the sorption of the metal ions,
      with the maximum uptake capacities ranging from 0.61 to 1.16 mmol/g for Sargassum
      sp. and 0.63 to 1.25 mmol/g for Padina sp. The general affinity sequence for
      Padina sp. was Pb>Cu>Cd>Zn>Ni, while that for Sargassum sp. was Pb>Zn>Cd>Cu>Ni.
      XPS and FTIR analysis of Sargassum sp. and Padina sp. revealed the chelating
      character of the ion coordination to carboxyl groups. It was confirmed that
      carboxyl, ether, alcoholic, and amino groups are responsible for the binding of
      the metal ions.

PMID- 15158391
TI  - Preparation, structure, and magnetic properties of polystyrene coated by Fe3O4
      nanoparticles.
AB  - A novel method of fabricating core-shell structure particles, comprising nearly
      monodisperse polystyrene (PS) spheres as cores and Fe3O4 as shells, is submitted.
      In this research, the magnetite (Fe3O4) shell was prepared by seeded growth from
      the reaction of FeCl2 with diethylene glycol (DEG) in aqueous solutions. The
      thickness of the shell were controlled in the range of 0-60 nm by using slow
      injection. The composition and the structure of the shell were characterized by X
      ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), thermogravimetric analysis (TG), and vibrating-sample
      magnetometry (VSM). It is found that there are some differences between the
      magnetic composite spheres shelled with Fe3O4 and pure Fe3O4 particles, such as
      the size of the magnetites and the ferromagnetic property. Furthermore, the
      spheres exhibited the superparamagnetic characterization when the thickness of
      the Fe3O4 shell was less than 15 nm.

PMID- 15158392
TI  - Stability of silicon and titanium carbide suspensions in electrolyte,
      poly(ethylene oxide), and PEO-surfactant solutions.
AB  - It has been shown that the coagulation values of counterions for SiC and TiC
      suspensions with particle radius from 0.5 to 5 microm obey a z(2.5-3.5) law and
      there is an insufficient change in the critical concentration of 1-1 electrolytes
      (CCE) when the surface potential of particles increases more than two times.
      Also, the CCE values hardly depend on the position of counterions in the
      lyotropic sequence. This is explained by aggregation of SiC and TiC particles at
      a secondary minimum, which is proved by calculations of the potential curves of
      interparticle interactions using the DLVO theory. The adsorption of poly(ethylene
      oxide) on the surfaces studied does not cause--in contradiction to dispersions
      with smaller particles--an unlimited growth in the stability of suspensions. This
      is due to the aggregation of large particles with adsorbed PEO, as in polymer
      free dispersions, under barrierless conditions in which the coordinates of the
      secondary minimum are determined by superposition of molecular attractive forces
      and steric repulsive forces of adsorbed polymeric chains, without a contribution
      from the electric repulsion term. PEO-anionic surfactant complexes possess higher
      stabilizing capacity compared to the individual components of the mixture. Our
      results show that the adsorbed polymer layers may hinder the aggregation both in
      the primary and in the secondary minimum for not very large particles only, the
      critical size of which depends on the dispersed phase nature and the molecular
      mass of the polymer.

PMID- 15158393
TI  - Dispersion of nanosized aqueous suspensions of barium titanate with ammonium
      polyacrylate.
AB  - The colloidal stability of nanosized barium titanate (BaTiO3) aqueous suspensions
      with ammonium polyacrylate (PAA-NH4) at different pH values has been investigated
      by means of zeta potential, adsorption isotherm, sedimentation, and rheology
      characterization. The isoelectric point of BaTiO3 powders is at pH 2.5 and the
      value of zeta potential is at its maximum near pH 10. The amount of leached
      barium ion decreases with increasing pH, but the change decreases with increasing
      initial pH. Adsorption of PAA-NH4 onto the surface of BaTiO3 decreases its zeta
      potential. Results show that PAA-NH4 adsorption follows Langmuir monolayer
      adsorption isotherms and the amount of PAA-NH4 required to stabilize nanosized
      BaTiO3 suspensions decreases as the pH increases. The mechanism of stabilization
      of BaTiO3 is shown to be electrosteric under the experimental conditions. Good
      agreement between zeta potential, sedimentation, and rheological tests is found,
      which identifies an optimum pH value of about 10 and an optimum dispersant
      concentration of about 2.0 wt%, independent of the solids volume fraction of
      suspensions.

PMID- 15158394
TI  - An NMR study of the freezing of emulsion-containing drops.
AB  - Various nuclear magnetic resonance (NMR) techniques were used to monitor the
      freezing behaviour of suspended 2-mm-diameter drops. The drops were composed of
      hydrocarbon oils emulsified in either water or water/sucrose mixtures. As such
      they were good model systems for the study of spray freezing, sharing structural
      similarities with potential products such as ice cream. In particular, simple 1H
      NMR spectroscopy was used to monitor and individually quantify the freezing or
      solidification behaviour of the various constituent species of the drops. In
      addition, the effect of freezing on the emulsion droplet size distribution (and
      hence emulsion stability) was also measured based on NMR self-diffusion
      measurements. The effect of freeze/thaw cycling was also similarly studied. The
      nucleation temperature of the emulsion droplets was found to depend on the
      emulsion droplet size distribution: the smaller the droplets, the lower the
      nucleation temperature. Emulsion droplet sizing indicated that oil-in-sucrose
      solution emulsions were more stable, showing minimal coalescence, whereas oil-in
      water emulsions showed significant coalescence during freezing and freeze/thaw
      cycling.

PMID- 15158395
TI  - An approach to the method for determination of surface potential on solid/liquid
      interface: theory.
AB  - The electrochemical properties on solid particle surfaces in an aqueous system
      have found wide application in many fields. However, for some of them there are
      no reliable methods of determination. What is particularly worth mentioning is
      the surface potentials of solid particles. Though this is a most important
      property and a most basic parameter in colloid interface electrochemistry, no
      reliable method for its determination is available yet. In the present paper,
      based on the diffuse double-layer theory, mathematical relations are constructed
      between the average concentration of ions positively adsorbed in the diffuse
      double layer and the surface potential of solid particles, thus transforming the
      determination of surface potential of solid particles into that of the average
      concentration of ions in the diffuse double layer, and then by applying the
      standard relationships of Gouy-Chapman theory, the mathematical relations of the
      average concentration of ions in the diffuse double layer with surface charge
      density, electrical field strength at surface, and specific surface area of solid
      particles are constructed.

PMID- 15158396
TI  - Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model
      for Gram-negative bacteria.
AB  - The antimicrobial activity of silver nanoparticles against E. coli was
      investigated as a model for Gram-negative bacteria. Bacteriological tests were
      performed in Luria-Bertani (LB) medium on solid agar plates and in liquid systems
      supplemented with different concentrations of nanosized silver particles. These
      particles were shown to be an effective bactericide. Scanning and transmission
      electron microscopy (SEM and TEM) were used to study the biocidal action of this
      nanoscale material. The results confirmed that the treated E. coli cells were
      damaged, showing formation of "pits" in the cell wall of the bacteria, while the
      silver nanoparticles were found to accumulate in the bacterial membrane. A
      membrane with such a morphology exhibits a significant increase in permeability,
      resulting in death of the cell. These nontoxic nanomaterials, which can be
      prepared in a simple and cost-effective manner, may be suitable for the
      formulation of new types of bactericidal materials.

PMID- 15158397
TI  - Formation of particles of metal hydroxides in water solution of polymer.
AB  - The stages of the formation of metal hydroxide particles in water medium were
      described. The first stage is the formation of complexes between the stabilizer
      and metal ion or of metal polyions containing a few metal ions. Dependence
      between the number of metal ions in polyion and its charge on the pH is
      described. The second stage is the formation of the metal hydroxide particles by
      the aggregation of polyions or their adsorption on/in the stabilizer. The
      distribution of the polyion number in the particles in polyion aggregation is
      described by the equation p(k) = k(ks-1)(k-1)/ksk and in polyion adsorption on/in
      the stabilizer particles is more narrow and is described by the equation p(k) =
      exp(-ks)/ks(-k)/k!, where k and ks are the number and the average number of
      polyions in the particle.

PMID- 15158398
TI  - Influence of pyrophosphate or polyethylene oxide on the aggregation and gelation
      of aqueous laponite dispersions.
AB  - The influence of pyrophosphate or polyethylene oxide (PEO) on the aggregation and
      gelation of dispersions of model disklike clay particles (Laponite) is studied
      using light scattering and rheology. Pyrophosphate adsorbs onto the positively
      charged rim and inhibits bond formation between the rim and the negatively
      charged faces of the particles. At low concentrations of pyrophosphate the
      aggregation of Laponite is only retarded, without significant modification of the
      structure of the aggregates and gels. The decrease of the aggregation rate can be
      explained by an increase of the energy barrier to the formation of bonds in
      proportion to the pyrophosphate concentration. Addition of a large amount of
      pyrophosphate leads to the breakup of Laponite aggregates and gels. PEO adsorbs
      onto the Laponite particles and inhibits aggregation by steric hindrance. The
      reduction of the aggregation rate depends on the molar mass and is maximal at
      about 1000 g/mol. Higher molar mass PEO bridges between the particles and leads
      to the formation of clusters or a weak gel immediately after mixture.

PMID- 15158399
TI  - Influence of adsorbing species on properties of equilibrium silver iodide
      clusters.
AB  - Thermodynamically stable AgI clusters were studied in the presence of high- and
      low-molecular-weight additives: polyethyleneimine (PEI) and dimethylformamide
      (DMF), respectively. Clusters containing up to 20 silver iodide pairs, roughly
      twice as many as in the system without PEI or DMF, have been observed. We show
      that the mechanism stabilizing these clusters is mixed adsorption with iodide
      ions at the AgI-electrolyte interface. We make it plausible that more strongly
      adsorbing additives give rise to ultralow interfacial tensions of the AgI
      electrolyte interface, with perspectives for "reversible colloids."

PMID- 15158400
TI  - The peculiarities of homogeneous nucleation of reactive Cu0 colloidal particles
      in the presence of functional oligoperoxides.
AB  - A method is proposed that combines the stage of formation of colloidal metal and
      metal-oxide particles with the stage of their surface modification by functional
      surface-active oligoperoxides (FSAP), which are sorbed irreversibly.
      Investigation of copper particle homogeneous nucleation kinetics witnesses the
      significant influence of supermolecular micelle-like structures formed by FSAP in
      solution on the reduction rate of Cu2+ cations caused by a phenomenon analogous
      to micellar catalysis. The rate constants of copper reduction in different local
      zones of the process have been determined. Particle homogeneous nucleation
      kinetics in the presence of surface-active oligoperoxides has been found to
      correspond to the main regularities of the Michaelis-Menten equation describing
      micellar catalysis. The carrying out of copper particle formation in distinct
      zones correlates well with the particle size distribution. The presence of
      reactive ditertiary peroxidic fragments on the particle surface as a result of
      FSAP sorption confers reliable protection from oxidation, hydrophobicity, and
      ability to form free radicals and participate in elementary stages of radical
      processes.

PMID- 15158401
TI  - pH-dependent surface charging and points of zero charge II. Update.
AB  - Recently published PZC (points of zero charge) of metal oxides and related
      materials are compiled to update the previous compilations (M. Kosmulski,
      Chemical Properties of Material Surfaces, Dekker, New York, 2001; J. Colloid
      Interface Sci. 253 (2002) 77). The electroacoustic method has been widely used;
      it has become a standard tool, and it has proved to produce IEP (isoelectric
      points) comparable with those obtained by means of classical electrokinetic
      methods. The recently published numerical values of PZC/IEP of various materials
      corroborate the old results, with one exception: the PZC of magnetite found at pH
      8 is substantially higher than the values reported in the old literature. New
      approaches to the electrokinetics of sparingly soluble salts have recently been
      proposed; e.g., the hysteresis in electrokinetic curves of (nominally) BaTiO3 has
      been interpreted in terms of changes in the surface stoichiometry caused by
      leaching.

PMID- 15158402
TI  - H2 generation during dry grinding of kaolinite.
AB  - H2 generation during mechanochemical treatment of kaolinite by dry grinding was
      examined by X-ray diffraction analysis, Fourier transform infrared spectroscopy,
      and BET surface area measurement. The H2 concentration in the mill pot, measured
      by gas chromatography, increased with grinding time up to a maximum concentration
      of 156 ppm (0.35 micromol) after 600 min. This H2 generation is considered to
      occur as a result of three processes: (1) structural destruction characterized by
      the delamination and loss of hydroxyl groups as a result of dry grinding, (2)
      transformation of liberated hydroxyls into water molecules by mechanochemical
      effects such as prototropy, and (3) H2 generation through reaction between
      surface water molecules and mechanoradicals created by the rupture of Si-O or Al
      O-Si bonds. Although the surface area plateaued after 240 min grinding, the H2
      concentration continued to increase, indicating that surface mechanoradicals are
      created during this later grinding stage. Thus, H2 generation can be used as an
      indicator of mechanoradical formation during mechanochemical treatment.

PMID- 15158403
TI  - Modification of surface crystal formation on mother crystal by additive
      molecules.
AB  - Additive molecules and excess reactant species (NaOH and NH4F) in NaF
      crystallization were used to control surface crystal formation on a mother
      crystal. When the surface integration was inhibited or bulk diffusion
      facilitated, more surface crystals were found on the mother crystal due to an
      increase in the interfacial supersaturation on the crystal. The inclusion of KCl
      as an additive and increases in the reactant concentration and agitation speed
      resulted in a higher population of surface crystals on the mother crystal,
      because surface integration was inhibited. However, surface crystal formation was
      suppressed by the polymer gelatin due to retardation of the bulk diffusion by the
      gelatin layer formed around the crystal. In addition, surface crystal formation
      significantly changed according to the feeding mode, and the excess species of
      NaOH originating from the NH4F feeding mode were more effective in facilitating
      surface crystal formation than the excess species of NH4F coming from the NaOH
      feeding mode due to the smaller ionic radii of NaOH than of NH4F.

PMID- 15158404
TI  - Effect of surfactants on the rate of solid-liquid mass transfer with gas
      generation at the interface.
AB  - The effect of Triton X-100 (nonionic surfactant) and cetyltrimethylammonium
      bromide (CTAB), cationic surfactant, on the mass transfer coefficient of the
      cathodic reduction of ferricyanide ions and anodic oxidation of ferrocyanide ions
      at hydrogen- and oxygen-evolving electrodes, respectively, was studied. It was
      found that the limiting current decreases by amounts ranging from 26.67 to 54.67%
      for Triton X-100 and from 20 to 46.0% for CTAB in the case of cathodic reduction
      of ferricyanide ions under natural convection at H2-evolving electrodes and from
      23.81 to 51.43% for Triton X-100 and from 18.10 to 40.95% for CTAB in the case of
      anodic oxidation of ferrocyanide ions under natural convection at O2-evolving
      electrodes, depending on the concentration of surfactant. Also the effects of
      Triton X-100 and CTAB on the gas hold-up and cell voltage were studied. The
      presence of surfactant in electrolytes was found to decrease the mass transfer
      coefficient by an amount ranging from 5.37 to 95.9%, depending on the operating
      conditions. Gas hold-up, cell voltage, and power consumption were found to
      increase in the presence of surfactant.

PMID- 15158405
TI  - The rhodamine B intercalation of montmorillonite.
AB  - Using photometric methods the dissociation constants and weight fractions of
      rhodamine B dimer in water solutions at different concentrations were determined.
      The montmorillonite (SWy) samples were fully intercalated with rhodamine B (RhB)
      solutions at various monomer/dimer ratios. The amount of rhodamine B in fully
      intercalated montmorillonite (RhB-SWy) increases with increasing concentration of
      dye in water solutions, i.e., with increasing dimer/monomer ratio. The sum of
      exchangeable guest cations in RhB-SWy is approximately constant (0.900 meq g(-1))
      for all samples, because RhB-SWy samples with prevailing dye monomer also contain
      higher amounts of non-exchanged alkali elements. The experimental data are
      supported by calculated structure models that illustrate the changes in RhB-SWy
      structure depending on monomeric and/or dimeric arrangement of guests. The
      analysis of the calculated structure models confirmed the existence of two phases
      with different basal spacings, d approximately 1.8 and approximately 2.3 nm,
      revealed by X-ray diffraction.

PMID- 15158407
TI  - Investigation of the effects of Au-colloid modification on cobalt
      hexacyanoferrate film growth and mass transport by electrochemical quartz crystal
      microbalance.
AB  - The growth of cobalt hexacyanoferrate (CoHCF) films on bare and Au-colloid
      modified electrodes in nitrate or sulfate solutions was monitored by
      electrochemical quartz crystal microbalance. The average efficiency of CoHCF film
      growth for Au colloid modified electrodes is 23 and 12 ng cm(-2) s(-1) in KNO3
      and K2SO4 solutions, respectively, while those values for the bare gold electrode
      are 15 and 9 ng cm(-2) s(-1), respectively. In K2SO4 solution, the apparent molar
      masses for the Au-colloid-modified electrode at lower and higher potential is
      58.4 and 37.3 g mol(-1), respectively, which is larger than those for the bare
      gold electrode (51.7 and 26.3 g mol(-1), respectively). The respective results
      were also obtained in KNO3 solution. Furthermore, the difference of the apparent
      molar masses at lower and higher potential for Au-colloid-modified electrodes is
      smaller than that for bare gold electrodes in the same electrolyte. Additionally,
      the mechanism of charge propagation is dependent on different anions in
      electrolyte solutions at higher potentials where the second redox reaction of
      CoHCF occurs. Therefore, the existence of Au colloids can accelerate CoHCF film
      growth and weaken the effect of anions on mass transport.

PMID- 15158406
TI  - Al2O3-coated 3-N-propylpyridinium chloride silsesquioxane polymer film:
      preparation and electrochemical property study of adsorbed cobalt
      tetrasulfophthalocyanine.
AB  - Porous Al2O3 presenting a specific surface area of SBET = 105 m2 g(-1) was coated
      with 3-N-propylpyridinium chloride silsesquioxane polymer. The ion exchange
      capacity of this polymer grafted onto an Al2O3 surface, resulting in a material
      designated as AlSiPy(+)Cl-, was 1.09 mmol g(-1). Furthermore, a cobalt(II)
      tetrasulfophthalocyanine anionic complex was immobilized on the chemically
      modified surface by an ion exchange reaction with a yield of 40 micromol g(-1)
      (the surface density of the electroactive species is 3.80 x 10(-11) mol cm(-2)).
      The electrochemical properties of the material obtained, AlSiPy/CoTsPc, were
      tested for the catalytic oxidation of oxalic acid at 0.77 V vs SCE in 1.0 mol l(
      1) KCl solution. Furthermore, a chronoamperometric technique was used with the
      electrode to test its potential use as a sensor for oxalic acid. The electrode
      response to oxalic acid concentrations between 1.0 and 3.5 mmol l(-1) was linear
      with an estimated detection limit of 0.5 mmol l(-1). The charge transfer
      resistance of the material, measured using the electrochemical impedance
      spectroscopy technique, was 43 Omega cm2.

PMID- 15158408
TI  - A stochastic model in liquid penetration through fibrous media.
AB  - The statistical genesis of the process of liquid penetration through fibrous
      media can be regarded as the interaction and the resulting balance among media
      and liquid cells that comprise the ensemble. A stochastic method, Ising's model,
      combined with Monte Carlo simulation, can therefore be employed in the study of
      liquid penetration through fibrous media. This process is driven by the
      difference of energy of the system after and before a liquid moves from one cell
      to the other. The energy of the system comprises the internal energy, work done
      by external force to the system, and the mechanical energy. For experimental
      verification, the process of water penetration through isotropic fiber mats, both
      spontaneously and under pressure, is examined. Simulation results are in good
      agreement with the experiments, indicating a good prospect of the method to be
      applied in this area.

PMID- 15158409
TI  - Influence of ammonium nitrate in phase transitions of Langmuir and Langmuir
      Blodgett films at air/solution and solid/solution interfaces.
AB  - The effect of ammonium nitrate on the phase transitions in Langmuir films of
      amphiphiles-stearic acid, stearyl amine (STAM), stearyl alcohol,
      dihexadecylphosphate, and the quarternized ammonium salt
      dioctadecyldimethylammonium bromide have been studied at air/water interface and
      in local ordering of their Langmuir-Blodgett films (LB films). The study shows
      that except for the stearyl amine (STAM) all other monolayers exhibit a liquid
      expanded to liquid-condensed transition with slight expansion in area in the
      presence of ammonium nitrate. STAM monolayers show a new phase transition, which
      possibly arises due to the differently ionized amino groups, and change in
      solvation sheath due to an ion-dipole type interaction between the amino groups
      and the ammonium ion in the subphase. Mixed films of the amine with the acid and
      alcohol did not show such intermediate phases indicating that competing H-bonds
      between polar groups themselves and dipolar couplings between the polar groups
      and ammonium nitrate play a major role in the organization of the molecules at
      the interface. The above effect resulting in a change in the local order is borne
      out by Brewster angle micrographs (BAM) of the Langmuir films of STAM at
      air/solution interface. Such behavior is also seen at solid/liquid interfaces
      where the polar component of surface energy undergoes a drastic change for the
      amine films transferred onto solid substrates from the air/ammonium nitrate
      solution interface.

PMID- 15158410
TI  - Fabricating high-quality opal films with uniform structure over a large area.
AB  - Films of opal, a colloidal crystalline lattice with closely packed structure, are
      anticipated to become a fundamental material in photonic crystal engineering. One
      of the technological issues is forming the opal film with a flat and uniform
      surface over a large area. This article describes a new and simple method for
      forming an opal film without special equipment. The opal film is formed by drying
      a colloidal suspension covered on a hydrophilic solid substrate. In the
      conventional method, a ring-shaped opal usually forms at the edge (contact line)
      of the suspension on the substrate. The new method improved the process of drying
      the colloidal suspension free from the ring formation. The driving force of this
      ring formation is based on capillary flow in the suspension from inside to
      outside because of the high evaporation rate at the contact line. To prevent
      capillary flow, the contact line of the suspension was covered with hydrophobic
      silicone liquid. As a result, ring formation was depressed and flat opal films
      with uniform structure were formed. The structure comprised cubic closely packed
      (111) planes, and the opal films were grown to grain sizes larger than 200
      microm. In addition, the coating area of the opal film was greater than 75 cm2
      using a 4-in. silicone wafer. This new method should be useful for coating high
      quality opal film over large areas on solid substrates.

PMID- 15158411
TI  - Surface tensions for isomeric chlorobutanes with isomeric butanols.
AB  - A drop volume tensiometer was employed to measure the surface tensions for the
      binary mixtures of each of the isomers of chlorobutane with each of the isomers
      of butanol at a temperature of 298.15 K. From these data the surface tension
      deviations were calculated. The results have been compared with the predictions
      obtained by the group contribution method proposed by Suarez.

PMID- 15158412
TI  - Bubble-size dependence of the critical electrolyte concentration for inhibition
      of coalescence.
AB  - The interaction of pairs of bubbles with equal diameters grown on adjacent
      capillaries in aqueous magnesium sulfate solutions is observed for varying
      electrolyte concentrations and bubble diameters. As in previous investigations, a
      sharp transition from coalescence to bubble detachment without coalescence is
      observed with increasing electrolyte concentration. The critical electrolyte
      concentration for this transition is found to increase with decreasing bubble
      diameter for bubble diameters of 1.4 to 4.2 mm.

PMID- 15158414
TI  - Interfacial tensiometry as a novel methodology for the determination of
      surfactant adsorption at a liquid surface.
AB  - At low surfactant concentration the loss of molecules in the bulk phase due to
      adsorption can be significant if the surface-area-to-bulk-volume ratio is large.
      This loss of molecules, however, can be used to determine the adsorption of a
      surfactant if the experiments are performed under well-controlled conditions.
      Experiments are performed with the model surfactant tridecyldimethylphosphine
      oxide (C13DMPO) using drop profile analysis and ring tensiometry. Taking into
      account the different area/volume ratios and the measured equilibrium surface
      tensions as a measure of the final surfactant bulk concentration, the adsorption
      of C13DMPO is determined.

PMID- 15158413
TI  - Hydrodynamically induced chemical oscillation at a water/nitrobenzene interface.
AB  - By measuring a time course of interfacial tension and interfacial electrical
      potential, we successfully observed oscillatory phenomena that were based on
      alternatively appearing adsorption and desorption processes of anionic surfactant
      molecules (sodium dodecyl sulfate (SDS)) at the water/nitrobenzene interface.
      These oscillation patterns were drastically modified by slightly changing the
      rate of SDS aqueous solution injection into the water phase. When 10 mM of SDS
      aqueous solution was injected at a low rate, for example, at less than 1
      microl/min, abrupt adsorption was repeatedly followed by slow desorption of DS-
      ions; in other words, the sequence of the oscillation and relaxation processes
      was repeated. However, when it was injected at a higher rate, no remarkable
      periodic phenomenon occurred after the first oscillation. In addition, the rapid
      adsorption process was observed to be accompanied by a flip motion of the
      liquid/liquid interface and a flow along the interface. This is caused by a
      Marangoni convection that is brought about by the generation of heterogeneity of
      interfacial tension. Furthermore, by estimating the flow speed, it was determined
      that the faster flow tends to quench the periodic oscillation patterns.

PMID- 15158415
TI  - Moving of a nonhomogeneous, porous floc normal to a rigid plate.
AB  - The boundary effect on the moving of a porous, nonhomogeneous, spherical floc
      normal to a rigid plate is analyzed theoretically for the case of low to medium
      Reynolds number. In particular, the drag force acting on the floc under various
      conditions is evaluated. A two-layer structure is adopted to simulate the
      nonhomogeneous nature of a floc. We show that if a floc is away from the plate,
      the streamlines surrounding the floc are distorted, but the degree of distortion
      becomes less significant if the floc is near the plate. The modified drag
      coefficient of a porous floc is orders of magnitude smaller than that of the
      corresponding rigid particle. For a fixed volume-averaged permeability, the
      effect of the presence of the plate on the behavior of a nonhomogeneous floc is
      more significant than that of a homogeneous floc, and this effect depends largely
      on the structure of a floc. The nonhomogeneous structure of a floc leads to a
      positive deviation from a Stokes-law-like correlation in the modified drag
      coefficient, and the smaller the volume-averaged permeability of a floc the
      greater the deviation. The presence of the plate has the effect of reducing this
      deviation. The nonhomogeneous structure of a floc on its modified drag
      coefficient is pronounced when it is close to a boundary.

PMID- 15158416
TI  - Electroacoustics in low-temperature ionic liquids.
AB  - Titanium dioxide was used as a model colloid to demonstrate the possibility of
      obtaining reliable values of the electrophoretic mobility in low-temperature
      ionic liquids. Mobilities as low as -0.98 +/- 0.16 x 10(-10) and -1.25 +/- 0.33 x
      10(-10) m2 V(-1) s(-1) were found in dry and wet 1-butyl-3-methylimidazolium
      triflate, respectively. These values are lower by two orders of magnitude than
      typical mobilities in stable aqueous dispersions due to a high viscosity of the
      ionic liquids.

PMID- 15158418
TI  - Stokes number effects in Lagrangian stochastic models of dispersed two-phase
      flows.
AB  - The statistical properties of fluid velocities along particle trajectories in
      turbulent flows have a conditional dependency upon particle velocity. It is shown
      that the formulation of Lagrangian stochastic (LS) models for particle
      trajectories in terms of the well-mixed condition for these conditional velocity
      statistics is exactly analogous to the formulation of second-order LS models for
      fluid-particle trajectories. The particle aerodynamic response time is shown to
      be incorporated at second order, which together with the Lagrangian timescale
      introduced at first order, defines the Stokes number. Reynolds-number effects can
      be incorporated at third order. The corresponding Fokker-Planck equation is shown
      to be identical to that advocated by Pozorski and Minier [Phys. Rev. E 59 (1999)
      855], who included the fluid velocities "seen" by a particle in the probability
      density function (pdf) formalism of Reeks and co-workers as a means of
      circumventing the closure problem (prescribing a closure for the particle flux
      induced by the fluid) associated with that approach. It is demonstrated that the
      neglect of Stokes-number effects accounts, in part, for the tendency of first
      order LS models to underpredict particle deposition velocities in the diffusion
      impaction regime.

PMID- 15158417
TI  - Fundamental limits of optical microrheology.
AB  - We estimate the fundamental limits of different microrheological techniques based
      on optical detection. It is suggested that particle tracking systems using
      nondifferential detection have a minimum detectable displacement given by
      0.2(lambda0/NA)(1/square root of (SNR)), where lambda0 is the wavelength, NA is
      the numerical aperture of the focusing objective, and SNR is the signal-to-noise
      ratio of the system. This limit has important consequences in microrheology,
      since the noise contributes with an apparent diffusion constant of Dl
      approximately 0.02(lambda0/NA)2(B/SNR), where B is the bandwidth of the detection
      unit. As the SNR of ordinary microscopes is limited, one should be extra careful
      when probing soft materials with low diffusion constants. On the other hand, in
      differential systems based on laser detection, the SNR is considerably increased
      due to reduced laser noise, and the minimum detectable displacement is given by
      0.4(lambda0/NA)(1/SNR). One may therefore expect to measure the diffusion
      constant with higher accuracy if the SNR is large. Finally, we find that total
      internal reflection microscopy (TIRM) has a minimum detectable displacement given
      by 0.1lambda0/SNR.

PMID- 15158419
TI  - Streaming current, permeability, and microelectrophoresis of polystyrene latices
      in methanol-ethanol mixtures.
AB  - The influence of the solvent (methanol-ethanol mixtures) on the electrokinetic
      behavior of polystyrene latices with sulfate groups was studied (methanol content
      was increased by 0.2 at a constant KBr concentration of 1 mM). Viscosity,
      density, and dielectric constant (eta, rho, and epsilon) were determined at
      experimental conditions. Two latices (with different surface charge densities and
      sizes) were used. Electrophoresis measurements were used for dilute dispersions.
      Streaming current and hydrodynamic permeability were measured for porous plugs.
      Linear trends in the electrokinetic measurements were observed in the whole molar
      fraction range. The experimental data obtained from different techniques allow
      determining the zeta potential according to a well-established classical
      relationship. The results obtained were analyzed on the basis of the solvent
      mixture properties and the electrical interface behavior. In addition,
      permeability data provided valuable information to interpret effects at the solid
      liquid interface of the porous plug.

PMID- 15158420
TI  - Effect of acidic treatment on metal adsorptions of pitch-based activated carbon
      fibers.
AB  - In this work, the pitch-based activated carbon fibers (ACFs) were prepared by
      nitric acid to investigate the multi-metal adsorption in interfacial and textural
      points of view. N2/77 K adsorption isotherm characteristics, including the
      specific surface area and micropore volume, were studied by BET specific surface
      area and t-plot methods, respectively. As a result, the specific surface area of
      the almost neutral ACFs in nature significantly decreased with nitric acid
      treatment, probably due to the widening of micropores. However the total acidity,
      including the carboxyl groups, on carbon surfaces was extremely induced during
      the acidic surface treatment. From the adsorptions of Cu2+ and Ni2+, it was
      revealed that the adsorption capacity of metal ions was mainly influenced by the
      weakly acidic functional groups such as lactones on the carbon surfaces at pH <
      pI (isoelectric point), and by the strongly acidic functional groups such as
      carboxyl groups at pH > pI.

PMID- 15158421
TI  - Delamination and restacking of hybrid layered double hydroxides assessed by in
      situ XRD.
AB  - Delamination and restacking of dodecyl-sulfate-intercalated hydrotalcite in CCl4
      and toluene were followed by in situ low-angle XRD. It is shown that exfoliation
      of hybrid layered double hydroxides must be rationalized in terms of the
      miscibility of the solvent and the aliphatic chains of the intercalated
      amphiphilic anions. The macroscopic appearance of diluted systems, however, is
      determined by the interaction between the edges of the exfoliated lamella.

PMID- 15158422
TI  - A developmental examination of gender differences in brain engagement during
      evaluation of threat.
AB  - BACKGROUND: Females appear to be more sensitive and responsive to social cues,
      including threat signals, than are males. Recent theoretical models suggest that
      developmental changes in brain functioning play important roles in the emergence
      of such gender differences. METHODS: We used functional magnetic resonance
      imaging to examine developmental and gender differences in activation of neural
      structures thought to mediate attention to emotional faces depicting varying
      degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and
      anterior cingulate cortex during the evaluation of threat conveyed by faces.
      Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned
      while they rated how threatening pictures of neutral and emotional (angry,
      fearful, or happy) faces appeared. RESULTS: Results indicate significant
      interactions among age, gender, and face type for activation during explicit
      threat monitoring. In particular, adult women activated orbitofrontal cortex and
      amygdala selectively to unambiguous threat (angry) cues, while adult men showed a
      less discriminating pattern of activation. No gender differences were evident for
      adolescents, who as a group resembled adult males. CONCLUSIONS: These findings
      suggest that there are gender differences in patterns of neural responses to
      emotional faces that are not fully apparent until adulthood.

PMID- 15158423
TI  - Fear conditioning in virtual reality contexts: a new tool for the study of
      anxiety.
AB  - BACKGROUND: Context conditioning has been suggested to model clinical anxiety,
      but context, as manipulated in animal models, has not been translated to human
      studies. A virtual environment might prove to be the ideal tool for innovative
      experimental paradigms to study explicitly cued fear and contextual anxiety in
      humans. METHODS: Subjects were guided through a virtual environment that
      consisted of two rooms connected by a street scene. In each of the rooms, a blue
      and a yellow panel on a wall served as explicit conditioned stimuli (CS). The
      panels were displayed several times. One of the panels (CS+) was associated with
      a shock in one of the rooms (shock room). No shock was administered in the other
      room (safe room). Acoustic startle stimuli were administered in the presence and
      in the absence of the panels to assess explicit cued conditioning to the CS and
      context conditioning to the rooms, respectively. RESULTS: Startle was potentiated
      by the CS+ in both rooms, which suggests generalization of fear across contexts.
      After acquisition, startle was potentiated in the shock room, compared with the
      safe room, in the absence of the CS+. CONCLUSIONS: These results support the
      future use of virtual reality to design new conditioning experiments to study
      both fear and anxiety.

PMID- 15158424
TI  - Reduced auditory efferent activity in childhood selective mutism.
AB  - BACKGROUND: Selective mutism is a psychiatric disorder of childhood characterized
      by consistent inability to speak in specific situations despite the ability to
      speak normally in others. The objective of this study was to test whether reduced
      auditory efferent activity, which may have direct bearings on speaking behavior,
      is compromised in selectively mute children. METHODS: Participants were 16
      children with selective mutism and 16 normally developing control children
      matched for age and gender. All children were tested for pure-tone audiometry,
      speech reception thresholds, speech discrimination, middle-ear acoustic reflex
      thresholds and decay function, transient evoked otoacoustic emission, suppression
      of transient evoked otoacoustic emission, and auditory brainstem response.
      RESULTS: Compared with control children, selectively mute children displayed
      specific deficiencies in auditory efferent activity. These aberrations in
      efferent activity appear along with normal pure-tone and speech audiometry and
      normal brainstem transmission as indicated by auditory brainstem response
      latencies. CONCLUSIONS: The diminished auditory efferent activity detected in
      some children with SM may result in desensitization of their auditory pathways by
      self-vocalization and in reduced control of masking and distortion of incoming
      speech sounds. These children may gradually learn to restrict vocalization to the
      minimal amount possible in contexts that require complex auditory processing.

PMID- 15158425
TI  - Maternal behavior modulates X-linked inheritance of behavioral coping in the
      defensive burying test.
AB  - BACKGROUND: Complex behavioral traits such as coping strategies in response to
      stress are usually formed by genetic and environmental influences. METHODS: By
      exploiting the phenotypic and genotypic differences between the Wistar Kyoto
      (WKY) and Fischer 344 (F344) inbred rat strains, we recently identified three X
      chromosome-linked quantitative trait loci contributing to differences in coping
      strategies in the defensive burying (DB) paradigm. In this article we study the
      influence of postnatal maternal environment in these behaviors by characterizing
      the maternal behavior of these strains and the effect of cross-fostering on DB
      behavior of male offspring from reciprocal crossing (F1). RESULTS: Maternal
      behavior of WKY rats can be quantitatively characterized by less contact and more
      periods of neglect of their F1 pups. In contrast, F344 mothers engaged in more
      active behaviors such as licking/grooming and arched-back nursing. Cross
      fostering male F1 pups at birth did not influence the latency to bury measure in
      DB; however, duration of burying and prod approaches were influenced by both
      genotype and maternal environment in an additive manner. CONCLUSIONS: These
      results demonstrate that different measures of behavioral coping in the DB
      paradigm are influenced by maternal environment to differing degrees and in
      addition by genetic factors.

PMID- 15158426
TI  - Reduction of anxiety after restricted feeding in the rat: implication for eating
      disorders.
AB  - BACKGROUND: Eating-disorder patients exhibit not only abnormal eating attitudes
      but also pathologic anxiety-like behaviors. The specific nature of the
      relationship between dieting and anxiety-like behavior is unknown. METHODS: To
      investigate the adaptational changes that resulted from chronic restricted
      scheduled feeding (2-hour access per day for 2 weeks) and subsequent free
      refeeding, longitudinal changes in the microstructure of feeding behavior were
      studied in male rats. To study the relationship between restricted feeding and
      anxiety-like behavior, separate rats were tested in the elevated plus-maze under
      the following conditions: 1) free feeding; 2) acute food restriction (2-hour
      access for 1 day); 3) chronic food restriction (for 10 days); or 4) postrecovery
      (after 10 days of free feeding subsequent to chronic food restriction). RESULTS:
      The effects of chronic food restriction on meal structure diminished within a few
      days after refeeding. Decreased anxiety-like behavior was seen during acute and
      chronic food restriction and did not reflect nonspecific behavioral activation.
      Anxiolytic-like effects persisted after 10 days of refeeding. CONCLUSIONS:
      Chronic food restriction produced reductions in anxiety-like behavior that
      persisted beyond the normalization of food intake patterns. The findings might
      have etiologic and pathophysiologic relevance for the restrained eating pattern
      in eating-disorder patients with comorbid anxious symptoms.

PMID- 15158427
TI  - The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model
      of drug relapse.
AB  - BACKGROUND: Brain noradrenaline is involved in footshock stress-induced
      reinstatement of drug seeking in a rat relapse model. We studied whether
      yohimbine, an alpha-2 adrenoceptor antagonist that increases noradrenaline
      release and induces anxiety-like responses in human and nonhuman subjects, would
      reinstate methamphetamine seeking in rats. METHODS: In experiment 1, the effect
      of yohimbine (1.25-2.5 mg/kg) on reinstatement was compared with that of
      intermittent footshock (5 min;.2-.6 mA) in rats that were trained to lever press
      for intravenous methamphetamine (9-11 days) and subsequently underwent 7 days of
      extinction training. In experiment 2, the effect of yohimbine on reinstatement of
      drug seeking was determined during early (1 day) and late (21 or 51 days)
      withdrawal periods. On the test days, rats were first given 3-hour extinction
      sessions and were then tested for reinstatement induced by yohimbine. RESULTS: In
      experiment 1, both yohimbine and footshock stress reinstated methamphetamine
      seeking after extinction. In experiment 2, extinction responding was higher after
      21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant
      time-dependent changes in yohimbine-induced reinstatement were observed.
      CONCLUSIONS: Results indicate that yohimbine is a potent stimulus for
      reinstatement of methamphetamine seeking in a rat relapse model.

PMID- 15158428
TI  - Serotonin transporter promoter and intron 2 polymorphisms: relationship between
      allelic variants and gene expression.
AB  - BACKGROUND: Two polymorphic regions of serotonin transporter (5-HTT) gene: a 44
      base pair (bp) insertion/deletion in the promoter region (5-HTTLPR) and a 17 bp
      variable number of tandem repeats in second intron (VNTR-2), seem to modulate the
      gene's transcription in allele-dependent manner. METHODS: We have earlier
      demonstrated association with 5-HTT gene in families multiply affected by
      schizophrenia. Here, we investigated separate and combined effects of VNTR-2 and
      5-HTTLPR on the rate of peripheral 5-HTT transcription in a sample of offspring
      from those families. Relative 5-HTT mRNA levels were determined in 53 permanent
      lymphoblast cell lines by semiquantitative real-time polymerase chain reaction
      using beta-actin as reference. RESULTS: Since the low-expressing alleles (short
      [S], 10) appeared to act dominantly, genotypes were grouped as "high-expressing"
      (long [L]/L, 12/12) versus "low-expressing" (S, 10). At both loci, nonsignificant
      differences in 5-HTT mRNA levels ( approximately 30%) were observed between
      "high"- and "low-expressing" genotypes. In order to search for the potential
      combined effect of 5-HTTLPR and VNTR-2, levels of 5-HTT mRNA were compared among
      three groups of samples having "low-expressing" genotype at none, one, or both
      loci. Increase in number of "low-expressing" genotypes significantly reduced
      relative 5-HTT gene expression (p <.02). CONCLUSIONS: Our results indicate weak
      individual influence, but possible combined effect, of 5-HTTLPR and VNTR-2
      polymorphisms on 5-HTT gene expression.

PMID- 15158429
TI  - Fluoxetine and olanzapine have synergistic effects in the modulation of
      fibroblast growth factor 2 expression within the rat brain.
AB  - BACKGROUND: The combination of the antidepressant fluoxetine (FLX) and the
      atypical antipsychotic olanzapine (OLA) appears to be more effective for the
      treatment of resistant depression than single drugs. We hypothesize that such
      combination may determine a specific modulation of neuroplastic genes, which
      could contribute to therapeutic activity. METHODS: We investigated the expression
      of the neurotrophic molecule basic fibroblast growth factor 2 (FGF-2) after acute
      or chronic administration of FLX and OLA, alone or in combination. Ribonuclease
      (RNase) protection assay and Western blot analysis were employed to determine FGF
      2 expression in different brain structures and to identify the intracellular
      pathways possibly involved in FGF-2 modulation. RESULTS: After single injection,
      we found that FGF-2 mRNA levels were selectively upregulated in the prefrontal
      cortex only when the two drugs were coadministered, an effect paralleled by a
      significant increase of phosphorylated protein kinase B (P-Akt) levels.
      Conversely, chronic treatment with a combination of FLX and OLA (FLX+OLA)
      increased FGF-2 mRNA levels in prefrontal cortex, as well as in hippocampus and
      striatum. CONCLUSIONS: Based on these data, we hypothesize a role of endogenously
      synthesized FGF-2 in the effects of FLX/OLA combination on brain function and
      plasticity, which could contribute to its superior efficacy for the treatment of
      resistant depression.

PMID- 15158430
TI  - Fluoxetine administration potentiates the effect of olanzapine on locus coeruleus
      neuronal activity.
AB  - BACKGROUND: As many as 30% of individuals diagnosed with depression are
      nonresponsive to traditional antidepressant medication. Augmentation and
      combination strategies have emerged in an attempt to address this issue. Atypical
      antipsychotics (e.g., olanzapine), when added to a selective serotonin reuptake
      inhibitor (e.g., fluoxetine) have shown great promise in the treatment of these
      treatment-resistant patients. As of yet, the precise neural mechanisms
      responsible for the beneficial clinical effect of these combinations are not
      completely understood. METHODS: Separate groups of rats received either saline or
      fluoxetine (10 mg/kg/day) for 24 hours or 3 weeks via subcutaneously implanted
      osmotic pumps. The effects of either intravenous saline or olanzapine (.3, 1.0,
      or 3.0 mg/kg) on locus coeruleus (LC) neuronal activity were then assessed via
      extracellular single-unit recordings. RESULTS: Acute administration of olanzapine
      produced a significant elevation of the firing rate and burst firing of LC cells,
      and chronic, but not acute, administration of fluoxetine decreased baseline and
      burst firing of LC cells; however, when given in combination, an interaction of
      fluoxetine and olanzapine was observed, with olanzapine causing a significantly
      greater increase in LC firing rate and burst firing after acute and chronic
      administration of fluoxetine. CONCLUSIONS: These results provide a potential
      neural mechanism for the beneficial clinical effects of the olanzapine/fluoxetine
      combination. The increase in baseline and burst firing of LC neurons in the
      groups receiving both fluoxetine and olanzapine would result in enhanced
      norepinephrine release in projection areas (e.g., prefrontal cortex), which could
      lead to a reduction in depressive symptoms.

PMID- 15158431
TI  - Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in
      posttraumatic stress disorder.
AB  - BACKGROUND: The aim of this study was to determine whether there is increased
      responsiveness to corticosteroids in posttraumatic stress disorder (PTSD) by
      examining the differential effects of dexamethasone (DEX) on the inhibition of
      lysozyme activity. METHODS: 60 mL of blood was withdrawn at 8:00 am, and
      mononuclear leukocytes were isolated from the blood of 26 men with, and 18 men
      without, PTSD. An aliquot of live cells was incubated with a series of
      concentrations of DEX to determine the rate of inhibition of lysozyme activity; a
      portion of cells was frozen for the determination of glucocorticoid receptors
      (GR). RESULTS: Subjects with PTSD showed evidence of a greater sensitivity to
      glucocorticoids as reflected by a significantly lower mean concentration (nmol/L)
      of dexamethasone at which 50% of lysozyme activity is inhibited (IC(50-DEX))
      (PTSD+ = 4.9 +/-.53; PTSD- group = 7.2 +/-.64). The lysozyme IC(50-DEX) was
      significantly correlated with age at exposure to the first traumatic event in
      subjects with PTSD (r =.44, n = 26, p =.025). The number of cytosolic
      glucocorticoid receptors was also correlated with age at exposure to the focal
      traumatic event (r = -.44, n = 25, p =.03) in PTSD. CONCLUSIONS: This is the
      first in vitro demonstration of an alteration in target tissue sensitivity to
      glucocorticoids in PTSD. The lower lysozyme IC(50-DEX) might be related to the
      risk factor of prior exposure to trauma.

PMID- 15158432
TI  - Comment on "Neuronavigated repetitive transcranial magnetic stimulation in
      patients with tinnitus: a short case series".

PMID- 15158434
TI  - The ErbB/HER receptor protein-tyrosine kinases and cancer.
AB  - The ErbB/HER protein-tyrosine kinases, which include the epidermal growth factor
      receptor, consist of a growth-factor-binding ectodomain, a single transmembrane
      segment, an intracellular protein-tyrosine kinase catalytic domain, and a
      tyrosine-containing cytoplasmic tail. The genes for the four members of this
      family, ErbB1-ErbB4, are found on different human chromosomes. Null mutations of
      any of the ErbB family members result in embryonic lethality. ErbB1 and ErbB2 are
      overexpressed in a wide variety of tumors including breast, colorectal, ovarian,
      and non-small cell lung cancers. The structures of the ectodomains of the ErbB
      receptors in their active and inactive conformation have shed light on the
      mechanism of receptor activation. The extracellular component of the ErbB
      proteins consists of domains I-IV. The activating growth factor, which binds to
      domains I and III, selects and stabilizes a conformation that allows a
      dimerization arm to extend from domain II to interact with an ErbB dimer partner.
      As a result of dimerization, protein kinase activation, trans
      autophosphorylation, and initiation of signaling occur. The conversion of the
      inactive to active receptor involves a major rotation of the ectodomain. The ErbB
      receptors are targets for anticancer drugs. Two strategies for blocking the
      action of these proteins include antibodies directed against the ectodomain and
      drugs that inhibit protein-tyrosine kinase activity. A reversible ATP competitive
      inhibitor of ErbB1 (ZD1839, or Iressa) and an ErbB1 ectodomain directed antibody
      (IMC-C225, or Erbitux) have been approved for the treatment of non-small cell
      lung cancer and colorectal cancer, respectively. An ErbB2/HER2 ectodomain
      directed antibody (trastuzumab, or Herceptin) has also been approved for the
      treatment of breast cancer. Current research promises to produce additional
      agents based upon these approaches.

PMID- 15158435
TI  - Endosome disruption enhances the functional nuclear delivery of Tat-fusion
      proteins.
AB  - Tat protein from human immunodeficiency virus can deliver biologically active
      proteins in vivo and is of considerable interest for protein therapeutics. The
      mechanism responsible for Tat-fusion protein internalization is still poorly
      understood and controversial. The punctuate distribution, timing, and temperature
      sensitivity observed in our experiments with Tat-fusion proteins are consistent
      with endocytosis. After a few hours, Tat-fusion proteins accumulated around the
      nucleus without any significant visible nuclear targeting. Using a Cre/Lox based
      functional assay, lysosomotropic agents known to disrupt endosome integrity,
      increased by up to 23-fold the nuclear delivery of functional Tat-Cre recombinase
      without increasing cell uptake in a similar fashion. This shows that endosome
      disruption can significantly increase Tat-fusion protein access to the cytosol
      and nucleus. In addition, we found that internalized Tat-fusion proteins
      persisted several hours and that inhibitors of lysosome acidification did not
      increase functional nuclear delivery of Tat-Cre. This suggests that Tat-fusion
      proteins enter via the endosomal pathway, circumvent lysosomal degradation, and
      are then sequestered in the periphery of the nucleus. Most importantly, our work
      indicates that an inadequate intracellular trafficking is the main factor
      limiting the efficiency of protein cargo delivery using Tat.

PMID- 15158436
TI  - 70-kDa-heat shock protein presents an adjustable lectinic activity towards O
      linked N-acetylglucosamine.
AB  - Numerous works demonstrated that the dynamic O-GlcNAc glycosylation could protect
      against the proteasomal degradation by modifying the target proteins and the
      proteasome itself. Considering that Hsp70 is a crucial component in the quality
      control of protein conformation in the proteasomal pathway, we investigated the
      possibility that Hsp70 physically interacts with O-GlcNAc proteins through a
      lectinic activity. First, we demonstrate that in HepG2 cells, Hsp70 can
      specifically bind to O-GlcNAc residues but also is itself modified by O-GlcNAc.
      Second, when cells were deprived of glucose (nutrient stress), Hsp70 lectinic
      activity markedly increased whereas its glycosylation dramatically decreased. On
      the other hand, a 42 degrees C thermic stress did not affect any of these
      features. Lastly, the nature of O-GlcNAc modified proteins co-immunoprecipitating
      with Hsp70 was similar for cells submitted to the thermic and to nutrient stress.
      These results strongly suggest that O-GlcNAc influences protein stability through
      specific interaction with 70-kDa-heat shock protein members.

PMID- 15158437
TI  - Determination of amino acid pairs sensitive to variants in human copper
      transporting ATPase 2.
AB  - In this study, we use our probabilistic approach to analyze the amino acid pairs
      in human copper-transporting ATPase 2 (ATP7B) in order to determine which amino
      acid pairs are more sensitive to 125 variants from missense mutant human ATP7B.
      The results show 97.6% of 125 variants occur at randomly unpredictable amino acid
      pairs, which account for 80.9% of amino acid pairs in ATP7B, and the chance of
      occurring of variant is about 9 times higher in randomly unpredictable amino acid
      pairs than in predictable pairs. Thus, the randomly unpredictable amino acid
      pairs are more sensitive to variants in human ATP7B.

PMID- 15158439
TI  - Anti-oxidant adaptation in the AML cells supersensitive to hydrogen peroxide.
AB  - The purpose of this study was to investigate the adaptive mechanisms of hydrogen
      peroxide-supersensitive AML cells against the reactive oxygen species (ROS).
      Their scavenging capacity against ROS was determined using a fluorometric probe
      in the doxorubicin-resistant AML-2/DX100 cell characterized by the down
      regulation of catalase. AML-2/DX100 cells had more scavenging capacity against
      endogenous pro-oxidants than did the parental cells AML-2/WT, suggesting that an
      anti-oxidant adaptation against ROS occurred. cDNA microarrays for 8000 human
      genes revealed that among 21 anti-oxidant genes, each four gene was up- and down
      regulated more than 1.5-fold in AML-2/DX100 compared with AML-2/WT. The mRNA
      expression of glutathione S-transferase Pi, peroxiredoxin 2, thioredoxin 2, and
      glutaredoxin was elevated whereas that of peroxiredoxin 3, metallothionein-1F,
      superoxide dismutase 2, and thioredoxin reductase 1 was depressed. The result
      indicates that the down-regulation of certain anti-oxidant mechanisms can be
      compensated for by the up- and down-regulation of the other anti-oxidant
      mechanisms.

PMID- 15158438
TI  - Cloning of a full-length cDNA of human testis-specific spermatogenic cell
      apoptosis inhibitor TSARG2 as a candidate oncogene.
AB  - A novel human gene full-length cDNA sequence-TSARG2 was identified from a human
      testis cDNA library using the SRG2 gene (GenBank Accession No. ), which was
      significantly up-regulated in cryptorchidism, as an electronic probe. TSARG2 was
      1223 bp in length. The putative protein encoded by this gene was 305 amino acids
      with a theoretical molecular weight of 34,751 and isoelectric point of 9.85. The
      sequence shared no significant homology with any known protein in databases
      except SRG2. Northern blot analysis revealed that 1.7 kb TSARG2 transcript was
      detected selectively in human testis. Furthermore, results of in situ
      hybridization assay confirmed that TSARG2 was expressed in seminiferous tubules,
      more precisely in spermatogonia and spermatocyte. No mutation was found by PCR
      SSCP in 122 cases of azoospermia, severe oligzoospermia, and cryptorchidism. The
      green fluorescence produced by pEGFP-C1/TSARG2 was detected on the nucleus of
      COS7 cells after 24h post-transfection. The pcDNA3.1(-)/TSARG2 plasmid was
      constructed and introduced into MCF7 cells by liposome transfection. TSARG2 can
      accelerate MCF7 cells to traverse the S-phase and enter the G2-phase compared
      with the control without transfection of TSARG2, which suggested that this gene
      plays an important role in the development of cryptorchid testis and is a testis
      specific apoptosis candidate oncogene.

PMID- 15158440
TI  - Reduced expression of Bax in ceramide-resistant HL-60 subline.
AB  - Ceramide, the backbone of sphingolipids, has been reported to be involved in
      various cellular responses including apoptosis. We recently established and
      characterized a C2-ceramide-resistant HL-60 subline designated HL-CR. HL-CR cells
      were resistant to not only ceramide but also anti-cancer drugs including
      daunorubicin, etoposide, and cytosine arabinoside. To elucidate the mechanisms by
      which HL-CR cells became resistant to various apoptosis-inducing stimuli, the
      levels of Bcl-2 family proteins, which play crucial roles in drug-induced
      apoptosis, were compared between HL-CR and parental HL-60 cells. Among Bcl-2
      family members, Bax, a pro-apoptotic Bcl-2 family protein, was highly expressed
      in HL-60 but was hardly detected in HL-CR cells. Transient transfection of bax
      expressing plasmid, but not the vector alone, induced apoptosis in HL-CR cells.
      These results suggest that reduced expression of Bax might play a role in
      resistance to various apoptosis-inducing stimuli in HL-CR cells.

PMID- 15158441
TI  - RNAi induction and activation in mammalian muscle cells where Dicer and eIF2C
      translation initiation factors are barely expressed.
AB  - Dicer plays an important role in the course of RNA interference (RNAi), i.e., it
      digests long double-stranded RNAs into 21-25 nucleotide small-interfering RNA
      (siRNA) duplexes functioning as sequence-specific RNAi mediators. In this study,
      we investigated the expression levels of Dicer and eIF2C1 approximately 4, which,
      like Dicer, appear to participate in mammalian RNAi, in various mouse tissues.
      Results indicate that the levels of eIF2C1 approximately 4 as well as Dicer are
      lower in skeletal muscle and heart than in other tissues. To see if RNAi could
      occur under such a condition with low levels of expression of Dicer and eIF2C1
      approximately 4, we examined RNAi activity in mouse skeletal muscle fibers. The
      results indicate that RNAi can be induced by synthetic siRNA duplexes in muscle
      fibers. We further examined RNAi activity during myogenic differentiation of
      mouse C2C12 cells. The data indicate that although the expression levels of Dicer
      and eIF2C1 approximately 4 decrease during the differentiation, RNAi can be
      induced in the cells. Altogether, the data presented here suggest that muscle
      cells retain the ability to induce RNAi, although Dicer and eIF2C1 approximately
      4 appear to be barely expressed in them.

PMID- 15158442
TI  - The lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase
      I: evidence for the impairment of neuropeptide degradation in late-infantile
      neuronal ceroid lipofuscinosis.
AB  - Late-infantile neuronal ceroid lipofuscinosis (CLN2), previously known as the
      late-infantile form of Batten disease, is a lysosomal storage disease which
      results from mutations in the gene that codes for tripeptidyl peptidase-I (TPP
      I). This disease is characterised by progressive neurodegeneration in young
      children although the molecular mechanisms responsible for neuronal cell death
      are unclear. TPP-I is an exopeptidase which removes N-terminal tripeptides from
      small peptides, including several peptide hormones. We report that the
      degradation of the neuropeptide, neuromedin B, by mouse brain cells is restricted
      to lysosomes and that the pattern of degradation products is consistent with a
      predominant role for TPP-I. Neuromedin B is degraded by a similar pathway in a
      mouse neuronal cell line and also in cultured human fibroblasts. A specific
      inhibitor of TPP-I is able to abolish neuromedin B degradation in a variety of
      cell types. Fibroblasts from CLN2 patients, which are deficient in TPP-I
      activity, are unable to degrade neuromedin B. These observations suggest that TPP
      I is the predominant proteolytic enzyme responsible for the intracellular
      degradation of neuromedin B. The inability of cells from CLN2 patients to degrade
      neuromedin B and other neuropeptides may contribute to the pathogenesis of the
      disease.

PMID- 15158443
TI  - Comparison of the pH-induced conformational change of different clostridial
      neurotoxins.
AB  - Clostridial neurotoxins are internalized inside acidic compartments, wherefrom
      the catalytic chain translocates across the membrane into the cytosol in a low pH
      driven process, reaching its proteolytic substrates. The pH range in which the
      structural rearrangement of clostridial neurotoxins takes place was determined by
      8-anilinonaphthalene-1-sulfonate and tryptophan fluorescence measurements. Half
      conformational change was attained at pH 4.55, 4.50, 4.40, 4.60, 4.40, and 4.40
      for tetanus neurotoxin and botulinum neurotoxin serotypes /A, /B, /C, /E, and /F,
      respectively. This similarity indicates the key residues for the conformation
      transition are strongly conserved. Acidic liposomes support the conformational
      rearrangement shifting the effect versus higher pH values, whereas zwitterionic
      liposomes do not. The disulfide bridge linking the light and the heavy chains
      together needs to be oxidized to allow toxin membrane insertion, indicating that
      in vivo its reduction follows exposure to the cytosol after penetration of the
      endosomal membrane.

PMID- 15158444
TI  - A high-throughput method for development of FRET-based indicators for
      proteolysis.
AB  - SCAT3 is a fluorescence resonance energy transfer (FRET)-based indicator for
      activity of caspase-3, which is composed of an enhanced cyan fluorescent protein,
      a caspase-3-sensitive linker, and an enhanced yellow fluorescent protein with
      efficient maturation property (Venus). Despite its considerable promise, however,
      greater responsivity of fluorescence to the proteolysis has been desired for
      better understanding of spatio-temporal pattern of the activation of caspase-3
      during apoptosis. In the present study, the length of linker regions of SCAT3 has
      been thoroughly optimized by use of a PCR technique. The bacterial colonies
      expressing the constructs were screened for high FRET efficiency using our home
      made fluorescence image analyzer. The FRET signal of an improved SCAT3 changed by
      about tenfold during apoptotic events in mammalian cells, enabling visualization
      of caspase-3 activation with better spatial resolution than before. This new high
      throughput method will be applicable to development and improvement of FRET-based
      indicators for proteolysis.

PMID- 15158445
TI  - Interaction of D-lactate dehydrogenase protein 2 (Dld2p) with F-actin:
      implication for an alternative function of Dld2p.
AB  - D-Lactate dehydrogenase protein 2 [Yeast 15 (1999) 1377; Biochem. Biophys. Res.
      Commun. 295 (2002) 910] was initially identified as the actin interacting protein
      2 (Aip2p) using a two-hybrid screen to search for proteins that interact with
      actin [Nat. Struct. Biol. 2 (1995) 28], but no other evidence indicating an
      interaction between Aip2p and actin cytoskeleton has been reported so far. During
      our search for the protein conformation modifying activity, we serendipitously
      identified Aip2p isolated from Saccharomyces cerevisiae as exhibiting an
      interaction with F-actin both in vitro and in vivo. Incubation with Aip2p
      facilitated the formation of the circular form of F-actin in vitro, which
      exhibited an aberrant trypsin susceptibility. Overexpression of Aip2p induced
      multi-buds in yeast cells, whereas reduced expression interfered with the
      formation of the cleavage furrow for the cell division, which was rescued by the
      introduction of wild-type Aip2p. While Aip2p-treated F-actin in the circular form
      was negligibly stained by rhodamine-labeled phalloidin (rhodamine-phalloidin) in
      vitro, rhodamine-phalloidin staining profiles in actin interacting protein 2 gene
      (AIP2)-modified cells suggested a correlation between the conformation of F-actin
      and the expression of Aip2p in vivo. AIP2-deleted cells became sensitive to
      osmotic conditions, a hallmark of actin dysfunction. Finally, immunoprecipitation
      of yeast cells using anti-Aip2p antibody demonstrated that Aip2p associates with
      actin. These properties suggest that Aip2p may interact with F-actin in vivo and
      play an important role in the yeast cell morphology.

PMID- 15158446
TI  - Rab11-FIP3 localises to a Rab11-positive pericentrosomal compartment during
      interphase and to the cleavage furrow during cytokinesis.
AB  - The Rab11-family interacting protein 3 (Rab11-FIP3), also known as Arfophilin and
      Eferin, is a Rab11 and ADP-ribosylation factor (ARF) binding protein of unknown
      function. Here, we sought to investigate the subcellular localisation and
      elucidate the function of Rab11-FIP3 in eukaryotic membrane trafficking.
      Utilising a polyclonal antibody specific for Rab11-FIP3, we have demonstrated by
      immunofluorescence microscopy that Rab11-FIP3 colocalises with Rab11 in a
      distinctive pericentrosomal location in A431 cells. Additionally, we found that
      Rab11-FIP3 localises to punctate vesicular structures dispersed throughout A431
      cells. We have demonstrated that both Rab11 and Rab11-FIP3 localise to the
      cleavage furrow during cytokinesis, and that Rab11-FIP3 localisation is dependent
      on both microtubule and actin filament integrity. We show that Rab11-FIP3 does
      not enter brefeldin A (BFA) induced membrane tubules that are positive for the
      transferrin receptor (TfnR). Furthermore, we show that expression of an amino
      terminally truncated mutant of Rab11-FIP3 (Rab11-FIP3((244-756))) does not
      inhibit transferrin (Tfn) recycling in HeLa cells. It is likely that Rab11-FIP3
      is involved in trafficking events other than Tfn trafficking; these may include
      the transport of endosomally derived membrane to the cleavage furrow during
      cytokinesis.

PMID- 15158447
TI  - Translocation and association of ROCK-II with RhoA and HSP27 during contraction
      of rabbit colon smooth muscle cells.
AB  - The focus of the paper is to understand the role of HSP27 in mediating the
      association of RhoA with ROCK-II in sustained contraction of smooth muscle cells
      from the rabbit colon. In circular smooth muscle cells; acetylcholine-induced
      contraction (10(-7)M) was associated with translocation of ROCK-II to the
      particulate fraction, which remained sustained at 4 min after stimulation
      (135.1+/-8.1% increase, P </= 0.05). There was also an increased association of
      ROCK-II with RhoA particulate fraction (147.46+/-9.31 and 148.22+/-9.41, n = 3, P
      </= 0.05) and with HSP27 (155.6+/-10.7% increase, P </= 0.05) in the particulate
      fraction. Pre-incubation of cells with Y27632 resulted in the inhibition of the
      association of ROCK-II with RhoA in the particulate fraction. Acetylcholine (10(
      7)M) induced sustained phosphorylation of MLC (122.75+/-9.97%, P </= 0.05 and
      174.65+/-28.36%, P </= 0.05 increase in the di phospho-MLC at 30s and 4 min,
      respectively), which was inhibited upon pre-incubation with Y27632. Results
      suggest that ROCK-II undergoes a translocation to the particulate fraction with
      RhoA and with HSP27, suggesting that translocation and association of ROCK-II
      with RhoA is mediated by HSP27. Maintenance of the functional association of RhoA
      with ROCK-II in the particulate fraction mediated by HSP27 appears to be
      important to retain MLC in the phosphorylated state and hence the sustained
      contraction.

PMID- 15158449
TI  - Induction of apoptosis by ionizing radiation and CI-1033 in HuCCT-1 cells.
AB  - CI-1033 is a quinazoline-based HER family tyrosine kinase inhibitor that is
      currently being evaluated as a potential anticancer agent. The present study
      examines the molecular mechanism by which CI-1033 induces apoptosis either as a
      single agent or in combination with radiation. Although CI-1033 alone did not
      induce apoptosis, the simultaneous exposure of cells to CI-1033 and radiation
      induced significant levels of apoptosis. The sequential treatment of cells with
      CI-1033 followed by radiation induced an even greater effect with 62.6% of cells
      undergoing apoptosis but this enhanced effect was not seen if cells were treated
      first with radiation and then CI-1033. The combination treatment induces
      apoptosis of HuCCT-1 via upregulation of FasL and Bid cleavage. These data
      suggest that modulation of the Fas-FasL pathway and activation of Bid could be
      useful for increasing the anti-tumor effect of CI-1033 in this type of cancer.

PMID- 15158448
TI  - Sall1, a causative gene for Townes-Brocks syndrome, enhances the canonical Wnt
      signaling by localizing to heterochromatin.
AB  - The Spalt (sal) gene family plays an important role in regulating developmental
      processes of many organisms. Mutations of human SALL1 cause the autosomal
      dominant disorder, Townes-Brocks syndrome (TBS), and result in ear, limb, anal,
      renal, and heart anomalies. Targeted deletion of mouse Sall1 results in kidney
      agenesis or severe dysgenesis. Molecular mechanisms of Sall1, however, have
      remained largely unknown. Here we report that Sall1 synergistically activates
      canonical Wnt signaling. The transcriptional activity of Sall1 is related to its
      nuclear localization to punctate nuclear foci (pericentromeric heterochromatin),
      but not to its localization or association with beta-catenin, the nuclear
      component of Wnt signaling. In contrast, the RNA interference of Sall1 reduces
      reporter activities of canonical Wnt signaling. The N-terminal truncated Sall1,
      produced by mutations often found in TBS, disturbs localization of native Sall1
      to heterochromatin, and also down-regulates the synergistic transcriptional
      enhancement for Wnt signal by native Sall1. Thus, we propose a new mechanism for
      Wnt signaling activation, that is the heterochromatin localization of Sall1.

PMID- 15158450
TI  - Metabotropic glutamate receptors are expressed in adult human glial progenitor
      cells.
AB  - Glial precursor cells (GPCs) are present in the adult human central nervous
      system (CNS) and they can be isolated and maintained in culture for in vitro
      studies. This study analysed expression of mGluR3 and mGluR5 metabotropic
      glutamate receptor (mGluR) mRNAs in GPCs. A2B5 surface antigen positive GPCs were
      isolated using immunomagnetic selection from dissociated temporal lobe
      subcortical white matter cells. The separated GPCs were maintained in cultures
      and characterised by immunoreactivity for the differentiation markers A2B5 and
      human platelet-derived growth factor-alpha receptor (PDGFalphaR). Reverse
      transcription followed by multiplex PCR analysis showed that the GPCs expressed
      both mGluR3 and mGluR5a mRNAs. Double immunostaining for glial progenitor markers
      and mGluR5 proteins demonstrated that all A2B5 and PDGFalphaR-positive cells were
      also positive for mGluR5. The results indicate that GPCs present in the adult
      human CNS express mGluR3 and mGluR5a. These neurotransmitter receptors may be
      involved in the proliferation and differentiation of glial cells.

PMID- 15158451
TI  - Phosphorylation of the mitochondrial protein Sab by stress-activated protein
      kinase 3.
AB  - Mitogen-activated protein kinases (MAPKs) transduce extracellular signals into
      responses such as growth, differentiation, and death through their
      phosphorylation of specific substrate proteins. Early studies showed the
      consensus sequence (Pro/X)-X-(Ser/Thr)-Pro to be phosphorylated by MAPKs. Docking
      domains such as the "kinase interaction motif" (KIM) also appear to be crucial
      for efficient substrate phosphorylation. Here, we show that stress-activated
      protein kinase-3 (SAPK3), a p38 MAPK subfamily member, localizes to the
      mitochondria. Activated SAPK3 phosphorylates the mitochondrial protein Sab, an in
      vitro substrate of c-Jun N-terminal kinase (JNK). Sab phosphorylation by SAPK3
      was dependent on the most N-terminal KIM (KIM1) of Sab and occurred primarily on
      Ser321. This appeared to be dependent on the position of Ser321 within Sab and
      the sequence immediately surrounding it. Our results suggest that SAPK3 and JNK
      may share a common target at the mitochondria and provide new insights into the
      substrate recognition by SAPK3.

PMID- 15158452
TI  - The exocyst localizes to the primary cilium in MDCK cells.
AB  - Primary cilia play a role in the maintenance of tubular epithelial
      differentiation and ciliary dysfunction can result in abnormal cyst formation,
      such as occurs in autosomal dominant polycystic kidney disease (ADPKD). We
      previously showed that the exocyst, an eight-protein complex involved in the
      biogenesis of polarity from yeast to mammals, is centrally involved in cyst
      formation [Mol. Biol. Cell. 11 (2000) 4259]. Here we show that the exocyst
      complex localizes to the primary cilium in Madin-Darby canine kidney (MDCK)
      tubular epithelial cells. We further show that the exocyst is overexpressed in
      both cell lines and primary cell cultures of ADPKD origin, suggesting that the
      exocyst may be involved in the pathogenesis of ADPKD.

PMID- 15158454
TI  - Zinc(II)-mediated inhibition of ribonuclease Sa by an N-hydroxyurea nucleotide
      and its basis.
AB  - Ribonuclease Sa (RNase Sa) is a secretory ribonuclease from Streptomyces
      aureofaciens. Herein, 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is shown to
      be a competitive inhibitor of catalysis by RNase Sa. Inhibition is enhanced by
      nearly 10-fold in the presence of Zn(2+), which could coordinate to the N
      hydroxyurea group along with enzymic residues. The carboxylate of Glu54 is the
      putative base that abstracts a proton from the 2' hydroxyl group during catalysis
      of RNA cleavage by RNase Sa. Replacing Glu54 with a glutamine residue has no
      effect on the affinity of N-hydroxyurea 1 for the enzyme, but eliminates the
      zinc(II)-dependence of that affinity. These data indicate that an N-hydroxyurea
      nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of RNase Sa, and
      suggest that the carboxylate of Glu54 is a ligand for that Zn(2+). These findings
      further the development of a new class of ribonuclease inhibitors based on the
      complex of an N-hydroxyurea nucleotide and zinc(II).

PMID- 15158453
TI  - Regulation of translation elongation and phosphorylation of eEF2 in rat
      pancreatic acini.
AB  - While pancreatic protein synthesis and the initiation of translation are
      regulated by hormones and neurotransmiters, whether the elongation process is
      also regulated is unknown. Stimulatory doses of cholecystokinin (CCK) (100 pM),
      bombesin (10 nM), and carbachol (10 microM) increased elongation rates (measured
      as ribosomal half-transit time) in pancreatic acini in vitro. At the same time
      these secretagogues reduced elongation factor 2 (eEF2) phosphorylation, the main
      factor known to regulate elongation, and increased the phosphorylation of the
      eEF2 kinase. The mTOR inhibitor rapamycin reversed the dephosphorylation of eEF2
      induced by CCK, as did treatment with the p38 MAPK inhibitor SB202190, the MEK
      inhibitor PD98059, and the phosphatase inhibitor calyculin A. Neither rapamycin,
      SB202190, PD98059 nor calyculin A had an effect on CCK mediated eEF2 kinase
      phosphorylation. Translation elongation in pancreatic acinar cells is likely
      regulated by eEF2 through the mTOR, p38, and MEK pathways, and modulated through
      PP2A.

PMID- 15158455
TI  - Laser-induced time-resolved photoacoustic calorimetry study on photo-dissociation
      of human and bovine oxyhemoglobin.
AB  - The dynamics of the enthalpy and volume changes related to the photo-dissociation
      of oxygen from human and bovine oxyhemoglobin are investigated by nanosecond time
      resolved photoacoustic calorimetry (PAC). The values of enthalpy and volume
      change associated with the above process are deltaH = 37.8 +/- 3 kcal/mol, deltaV
      = 5.0 +/- 1 ml/mol for human HbO(2); and deltaH = 35.7 +/- 3.5 kcal/mol, deltaV =
      4.8 +/- 1 ml/mol for bovine HbO(2), respectively. A possible explanation for the
      similar values between both human and bovine oxyhemoglobin is proposed. In
      addition, the PAC results for human HbO(2) and HbCO are compared and discussed.

PMID- 15158456
TI  - Involvement of clusterin in 15-deoxy-delta12,14-prostaglandin J2-induced vascular
      smooth muscle cell differentiation.
AB  - To establish an in vitro model of vascular smooth muscle cell (VSMC)
      differentiation, we examined the effect of 15-deoxy-delta12,14-prostaglandin J(2)
      (15d-PGJ(2)) on the expression of VSMC differentiation markers. After the
      addition of 15d-PGJ(2) to confluent human umbilical artery smooth muscle cells
      synchronized in the G(0) phase, cells showed a "hill and valley" appearance and
      thereafter aggregated and formed macroscopic nodules. Cells forming nodules
      expressed high levels of SM2, the most specific VSMC differentiation marker,
      comparable to medial VSMCs in vivo. 15d-PGJ(2) significantly increased the mRNA
      and protein expression levels of clusterin, a secreted glycoprotein reported to
      induce nodule formation and differentiation of VSMCs. Moreover, addition of an
      anti-clusterin antibody completely inhibited the nodule formation induced by 15d
      PGJ(2) and induced apoptosis. Our results suggested that clusterin is involved in
      15d-PGJ(2)-induced nodule formation and cell differentiation in VSMCs.

PMID- 15158458
TI  - Cold exposure induces tyrosine phosphorylation of BIT through NMDA receptors in
      the rat hypothalamus.
AB  - The hypothalamus has a central role in maintaining homeostases of physiological
      conditions including body temperature and energy balance. To examine molecular
      responses to cold exposure in the hypothalamus, we examined changes in protein
      tyrosine phosphorylation in the suprachiasmatic nucleus of the hypothalamus after
      acute cold exposure in rats. It was found that brain immunoglobulin-like molecule
      with tyrosine-based inhibitory motifs (BIT, also called SHPS-1, SIRPalpha or
      p84), a transmembrane glycoprotein with two ITIM motifs, showed enhanced tyrosine
      phosphorylation after cold exposure. Its tyrosine phosphorylation induced by cold
      exposure was also found in other hypothalamic nuclei including the
      paraventricular nucleus, lateral hypothalamic area, ventromedial hypothalamus,
      and arcuate nucleus. This phosphorylation was blocked by AP-5, an NMDA receptor
      antagonist, indicating that it was mediated by NMDA receptors. These results
      suggest that BIT is involved in the mechanism of neuronal responses to cold
      exposure in the hypothalamus.

PMID- 15158457
TI  - TcZFP1: a CCCH zinc finger protein of Trypanosoma cruzi that binds poly-C
      oligoribonucleotides in vitro.
AB  - We have identified two zinc finger proteins of Trypanosoma cruzi, the protozoan
      parasite that causes Chagas disease in humans. These proteins, named tcZFP1 and
      tcZFP2, share the unusual zinc finger motif (CCCH) found in a diverse range of
      RNA-binding proteins involved in various aspects of the control of cell
      homeostasis and differentiation. We report here the functional expression of a
      recombinant tcZFP1, and the relative affinity and stability of the specific
      complexes formed between the protein and synthetic oligoribonucleotides
      containing C-rich sequences.

PMID- 15158459
TI  - A simple method for selection of trypsin chromogenic substrates using
      combinatorial chemistry approach.
AB  - A tetrapeptide combinatorial library, considered as chromogenic substrates of
      bovine beta-trypsin, was synthesized by the solid phase method. The peptides
      contain an analog of p-nitroanilide, obtained by attaching 5-amino-2-nitrobenzoic
      acid (Anb(5,2)) to the C-termini. Deconvolution of the peptide library, performed
      in solution using an iterative method, yielded four efficient trypsin substrates.
      The most active one, Phe-Val-Pro-Arg-Anb(5,2)-NH(2), appeared to be 125-fold more
      active than Bz-D,L-Arg-pNA (BAPNA) used as a reference compound. The reported
      method of designing trypsin chromogenic substrate libraries is straightforward.
      Such p-nitroanilides may be useful for the investigation of any protease
      substrate specificity.

PMID- 15158460
TI  - A recombinant adenoviral vector encoding functional vasoactive intestinal
      peptide.
AB  - Vasoactive intestinal peptide (VIP) is a small neuropeptide, which exerts
      pleiotropic functions. Based on its immunomodulatory, secretory, and possibly
      trophic effects, VIP is a valuable candidate molecule for the management of
      autoimmune disease. The purpose of this study was to develop a recombinant viral
      vector capable of directing the expression of functional VIP. The vector
      rAd5CMVhVIP was constructed and used to infect 293 cells. VIP expression was
      measured by an ELISA and function was evaluated by measurement of intracellular
      cAMP formation. rAd5CMVhVIP directed VIP expression and the transgenic VIP
      elicited a dose-dependent increase of intracellular cAMP, mediated through the
      VIP receptor VPAC(1). This is the first report showing the construction of a
      recombinant viral vector encoding biologically active VIP.

PMID- 15158461
TI  - Expression analysis of PCSTE3, a putative pheromone receptor from the lung
      pathogenic fungus Pneumocystis carinii.
AB  - The fungal pathogen Pneumocystis carinii remains the most prevalent opportunistic
      infection in patients infected with HIV. Fungal pheromone receptors are seven
      transmembrane domain G-protein-coupled receptors which are expressed on specific
      mating types, and have ligand-binding extracellular domains for specific
      pheromones from cells of the opposite mating type. We have cloned and
      characterized PCSTE3 from P. carinii, which encodes a seven transmembrane domain
      protein orthologous to the Saccharomyces cerevisiae pheromone receptor Ste3. We
      detect PCSTE3 by indirect immunofluorescence using antibodies designed to
      extracellular domains of the receptor in yeast expressing the protein. Using a
      downstream Fus1-lacZ reporter gene, we determined that PCSTE3 does not recognize
      a- or alpha-factor pheromones as ligands for the receptor. We isolated P. carinii
      life cycle stages and examined PCSTE3 expression by immunofluorescence microscopy
      and flow cytometry, and found PCSTE3 expression exclusively on a population of
      trophic forms. PCSTE3 receptor expression was not found on cysts.

PMID- 15158462
TI  - Contribution of the SgIGSF adhesion molecule to survival of cultured mast cells
      in vivo.
AB  - Spermatogenic immunoglobulin superfamily (SgIGSF) is a recently identified
      adhesion molecule, and the microphthalmia transcription factor (MITF) was
      essential for its expression in mast cells. Since the tg mutant allele is
      practically a null mutation of the MITF gene, cultured mast cells (CMCs) derived
      from (WBxC57BL/6)F(1) (F(1))-tg/tg mice did not express SgIGSF whereas CMCs from
      F(1)-wild-type (+/+) mice expressed it abundantly. When cocultured with NIH/3T3
      fibroblasts, F(1)-tg/tg CMCs showed poor adhesion to NIH/3T3 fibroblasts. When
      injected intraperitoneally, F(1)-tg/tg CMCs showed poor survival in the
      peritoneal cavity of mast cell-deficient F(1)-W/Wv mice. SgIGSF was expressed in
      tg/tg CMCs ectopically through retroviral transfection and through expression of
      a transgene. The resulting tg/tg CMCs showed not only a better adhesion to
      NIH/3T3 fibroblasts but also a better survival in the peritoneal cavity than
      control F(1)-tg/tg CMCs. SgIGSF-mediated adhesion seemed to play a role in the
      survival of CMCs in the peritoneal cavity.

PMID- 15158463
TI  - Bright fluorescence of a novel protein from Vibrio vulnificus depends on NADPH
      and the expression of this protein is regulated by a LysR-type regulatory gene.
AB  - A blue fluorescent protein, BfgV, belonging to the short-chain
      dehydrogenase/reductase superfamily, was found in a non-bioluminescent pathogen
      Vibrio vulnificus CKM-1. This protein has fluorescence spectra with two
      excitation peaks at 283 and 352 nm, and one emission peak at 456 nm. BfgV
      fluoresces through effectively augmenting the intrinsic fluorescence of NADPH
      bound to it. Escherichia coli transformants expressing this protein can emit eye
      detectable fluorescence. A LysR-type transcriptional regulator gene bfgR was
      found at the vicinal upstream region of bfgV in CKM-1 genome. The clues that
      products of bfgR can specifically bind to bfgR-bfgV intergenic promoter region
      and the deletion of bfgR significantly decreases the expression of bfgV reveal
      bfgR is a repressor gene of bfgV in V. vulnificus CKM-1.

PMID- 15158464
TI  - Myosin X transports Mena/VASP to the tip of filopodia.
AB  - Myosin X (M10) is a two-headed actin based motor expressed in a variety of cell
      types, that is thought to play a role in cargo movement in mammalian cells, but
      its cellular function is unknown. Here we found that M10 binds to Mena/VASP,
      which facilitates actin polymerization by competing with actin capping proteins.
      Immunocytochemistry revealed that endogenous M10 co-localized with Mena/VASP at
      the tip of filopodia. Consistently, both EGFP-M10 and RFP-VASP were found at the
      tip of filopodia. The result raises a hypothesis that M10 transports Mena/VASP
      towards the tip of filopodia. Supporting this idea, the amount of VASP at the tip
      of filopodia was proportional to that of M10. Furthermore, we directly visualized
      the movement of M10 and VASP in living HeLa cells under fluorescence microscope.
      EGFP-M10 and RFP-VASP move together from the root to the tip of the filopodia.
      Interestingly, the amount of M10 at the tip of filopodia was linearly related to
      the length of filopodia, consistent with the actin filament extending function of
      VASP. These results show that M10 is a specific motor carrying Mena/VASP from the
      root to the tip of the filopodia where extension of actin filament takes place.

PMID- 15158465
TI  - Identifying gp85-regions involved in Epstein-Barr virus binding to B-lymphocytes.
AB  - Epstein-Barr virus lacking glycoprotein gp85 cannot infect B-cells and epithelial
      cells. The gp85 belongs to the molecular complex required for virus invasion of B
      lymphocyte or epithelial cells. Moreover, there is evidence that gp85 is
      necessary for virus attachment to epithelial cells. Thirty-six peptides from the
      entire gp85-sequence were tested in epithelial and lymphoblastoid cell line
      binding assays to identify gp85-regions involved in virus-cell interaction. Five
      of these peptides presented high binding activity to Raji, Ramos, P3HR-1, and
      HeLa cells, but not to erythrocytes; Raji-cell affinity constants were between 80
      and 140nM. Of these five peptides, 11435 ((181)TYKRVTEKGDEHVLSLVFGK(200)), 11436
      ((201)TKDLPDLRGPFSYPSLTSAQ(220)), and 11438 ((241)YFVPNLKDMFSRAVTMTAAS(260))
      bound to a 65kDa protein on Raji-cell surface. These peptides and antibodies
      induced by them (recognising live EBV-infected cells) inhibited Epstein-Barr
      virus interaction with cord blood lymphocytes. It is thus probable that gp85
      regions defined by peptides 11435, 11436, and 11438 are involved in EBV invasion
      of B-lymphocytes.

PMID- 15158466
TI  - Molecular evolution of the ATPase subunit of three archaeal sugar ABC
      transporters.
AB  - The sequence of genes encoding extracellular amylopullulanase and putative
      maltodextrin ATP binding cassette (ABC) transporter of a hyperthermophilic
      archaeon, Thermococcus litoralis, was determined. The mdxK gene, which encodes an
      ATPase subunit of the putative maltodextrin ABC transporter, has extraordinarily
      high similarity with the malK gene, which encodes an ATPase subunit of
      trehalose/maltose ABC transporter of the same organism. DNA sequence comparison
      revealed that the malK gene was generated through the duplication of the mdxK
      gene before lateral gene transfer of the mal gene cluster from T. litoralis to
      Pyrococcus furiosus.

PMID- 15158467
TI  - Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma
      during adipogenesis.
AB  - Treatment of 3T3-L1 preadipocytes with differentiation inducers triggers a
      cascade in which C/EBPbeta is rapidly expressed, followed by C/EBPalpha and
      PPARgamma. C/EBPalpha and PPARgamma then activate the expression of adipocyte
      genes that produce the differentiated phenotype. Circumstantial evidence
      indicates that C/EBPbeta activates transcription of the C/EBPalpha and PPARgamma
      genes, both of which possess C/EBP regulatory elements in their proximal
      promoters. Although C/EBPbeta is expressed immediately upon induction of
      differentiation, acquisition of DNA binding activity is delayed for approximately
      14h. Chromatin immunoprecipitation (ChIP) analysis conducted 24h after induction
      revealed that C/EBPbeta binds to C/EBP regulatory elements in the proximal
      promoters of the C/EBPalpha and PPARgamma genes. After an additional delay ChIP
      analysis showed that C/EBPalpha binds to its own promoter and to the promoters of
      the PPARgamma and 422/aP2 genes. These findings support the view that once
      expressed, C/EBPalpha is responsible for maintaining the expression of PPARgamma
      and C/EBPalpha, as well as adipocyte proteins (e.g., 422/aP2) in the terminally
      differentiated state. Together these findings provide compelling evidence that
      C/EBPbeta, C/EBPalpha, and PPARgamma participate in a cascade during
      adipogenesis.

PMID- 15158468
TI  - A molecular beacon assay for measuring base excision repair activities.
AB  - The base excision repair (BER) pathway plays a key role in protecting the genome
      from endogenous DNA damage. Current methods to measure BER activities are
      indirect and cumbersome. Here, we introduce a direct method to assay DNA excision
      repair that is suitable for automation and industrial use, based on the
      fluorescence quenching mechanism of molecular beacons. We designed a single
      stranded DNA oligonucleotide labelled with a 5'-fluorescein (F) and a 3'-Dabcyl
      (D) in which the fluorophore, F, is held in close proximity to the quencher, D,
      by the stem-loop structure design of the oligonucleotide. Following removal of
      the modified base or incision of the oligonucleotide, the fluorophore is
      separated from the quencher and fluorescence can be detected as a function of
      time. Several modified beacons have been used to validate the assay on both cell
      free extracts and purified proteins. We have further developed the method to
      analyze BER in cultured cells. As described, the molecular beacon-based assay can
      be applied to all DNA modifications processed by DNA excision/incision repair
      pathways. Possible applications of the assay are discussed, including high
      throughput real-time DNA repair measurements both in vitro and in living cells.

PMID- 15158470
TI  - Many commonly used siRNAs risk off-target activity.
AB  - Using small interfering RNA (siRNA) to induce sequence specific gene silencing is
      fast becoming a standard tool in functional genomics. As siRNAs in some cases
      tolerate mismatches with the mRNA target, knockdown of genes other than the
      intended target could make results difficult to interpret. In an investigation of
      359 published siRNA sequences, we have found that about 75% of them have a risk
      of eliciting non-specific effects. A possible cause for this is the popular BLAST
      search engine, which is inappropriate for such short oligos as siRNAs.
      Furthermore, we used new special purpose hardware to do a transcriptome-wide
      screening of all possible siRNAs, and show that many unique siRNAs exist per
      target even if several mismatches are allowed. Hence, we argue that the risk of
      off-target effects is unnecessary and should be avoided in future siRNA design.

PMID- 15158469
TI  - AU-rich elements in the mRNA 3'-untranslated region of the rat receptor for
      advanced glycation end products and their relevance to mRNA stability.
AB  - Several putative polyadenylation sequences and an adenylate plus timidylate rich
      element (ARE) are present at the 3' end of the rat advanced glycation end
      products receptor (RAGE) gene. Two transcripts are generated by the use of
      alternative polyadenylation sequences, one containing the ARE sequence in its 3'
      untranslated region (3'-UTR). Transfections of CHO-k1 or NRK cells with
      constructs expressing the 3'-UTRs of the transcripts fused to a green
      fluorescence protein mRNA show that the ARE sequence has a negative effect on
      protein expression correlating with a decrease in the amount of mRNA, as shown in
      CHO-k1 transfected cells. When transfected cells were incubated in the presence
      of Actinomycin D the amount of fluorescence decreased in cells transfected with
      the ARE sequence, indicating that this sequence induces lower mRNA stability.
      Thus, alternative polyadenylation signals and an ARE sequence provide a novel
      mechanism for the regulation of the rat RAGE gene expression.

PMID- 15158471
TI  - Improved and automated prediction of effective siRNA.
AB  - Short interfering RNAs are used in functional genomics studies to knockdown a
      single gene in a reversible manner. The results of siRNA experiments are highly
      dependent on the choice of siRNA sequence. In order to evaluate siRNA design
      rules, we collected a database of 398 siRNAs of known efficacy from 92 genes. We
      used this database to evaluate previously proposed rules from smaller datasets,
      and to find a new set of rules that are optimal for the entire database. We also
      trained a regression tree with full cross-validation. It was however difficult to
      obtain the same precision as methods previously tested on small datasets from one
      or two genes. We show that those methods are overfitting as they work poorly on
      independent validation datasets from multiple genes. Our new design rules can
      predict siRNAs with efficacy >/= 50% in 91% of cases, and with efficacy >/=90% in
      52% of cases, which is more than a twofold improvement over random selection.
      Software for designing siRNAs is available online via a web server at or as a
      standalone version for high-throughput applications.

PMID- 15158472
TI  - The RING domain of PIASy is involved in the suppression of bone morphogenetic
      protein-signaling pathway.
AB  - Bone morphogenetic proteins (BMPs) play central roles in differentiation,
      development, and physiologic tissue remodeling. Recently, we have demonstrated
      that a protein inhibitor of activated STAT, PIASy, suppresses TGF-beta signaling
      by interacting with Sma and MAD-related protein 3 (Smad3). In this study, we
      examined a PIASy-dependent inhibitory effect on BMP signaling. PIASy expression
      was induced by BMP-2 stimulation and suppressed BMP-2-dependent Smad activity in
      hepatoma cells. Furthermore, BMP-2-regulated Smads directly bound to PIASy. We
      also demonstrated that the RING domain of PIASy played an important role in PIASy
      mediated suppression of Smad activity. We here provide evidence that the
      inhibitory action of PIASy on BMP-regulated Smad activity was due to direct
      physical interactions between Smads and PIASy through its RING domain.

PMID- 15158473
TI  - Following the rule: formation of the 6-helix bundle of the fusion core from
      severe acute respiratory syndrome coronavirus spike protein and identification of
      potent peptide inhibitors.
AB  - Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is a newly
      identified member of Family Coronaviridae. Coronavirus envelope spike protein S
      is a class I viral fusion protein which is characterized by the existence of two
      heptad repeat regions (HR1 and HR2) (forming a complex called fusion core). Here
      we report that by using in vitro bio-engineering techniques, SARS-CoV HR1 and HR2
      bind to each other and form a typical 6-helix bundle. The HR2, either as a
      synthetic peptide or as a GST-fusion polypeptide, is a potent inhibitor of virus
      entry. The results do show that SARS-CoV follows the general fusion mechanism of
      class I viruses and this lays the ground for identification of virus fusion/entry
      inhibitors for this devastating emerging virus.

PMID- 15158474
TI  - An excised patch membrane sensor for arachidonic acid released in mouse
      hippocampal slices under stimulation of L-glutamate.
AB  - An excised patch membrane sensor for arachidonic acid (AA) is described, whose
      response stems from AA-induced channel-type transport of ions across the excised
      patch membrane. The patch membrane sensor was prepared in situ by excising mouse
      hippocampal cell membranes with patch pipets having a tip diameter of < 0.5
      microm. The sensor responds to AA, giving rise to a channel-type current, and its
      magnitude (apparent conductance) increased with increasing AA concentration in
      the range from 10 to 30 nM. The detection limit was 2.1 nM (S/N = 3). The
      induction of channel-type currents was selective to AA over fatty acids such as
      palmitic acid, stearic acid, oleic acid, gamma-linolenic acid, and
      docosahexaenoic acid and AA metabolites such as 12-HETE, 5-HETE, and
      prostaglandin D(2). The sensor was applied to quantification of AA released from
      various neuronal regions (CA1, CA3, and DG) of mouse hippocampus under
      stimulation of 100 microM L-glutamate. The release of AA from each region was
      observed 1 min after the stimulation and the concentration of AA 5 min after the
      stimulation varied among the neuronal sites, i.e., 8+/-1 nM (n = 5) for CA1, 15+/
      3 nM (n = 3) for CA3, and 6+/-2 nM (n = 9) for DG. The L-glutamate-evoked release
      of AA was partly inhibited by ionotropic glutamate receptor antagonists (APV and
      DNQX) and completely blocked by phospholipase A2 (PLA2) inhibitor (MAFP),
      suggesting that the release of AA occurred by glutamate receptor-mediated
      activation of PLA2. The potential use of the present sensor for detecting local
      concentration of AA at various neuronal sites is discussed.

PMID- 15158475
TI  - Screening for topoisomerase I binding compounds by high-performance liquid
      chromatography-mass spectrometry.
AB  - A new rapid compound screening approach for topoisomerase I binding activity is
      presented. DNA topoisomerase I is used as a target protein to capture binding
      compounds from a mixture of combinatorial compounds by bioaffinity
      ultrafiltration. Using high-performance liquid chromatography combined with
      electrospray ionization mass spectrometry, small-molecule active compounds were
      identified. We also have successfully applied this method to identifying
      compounds from cells grown in culture.

PMID- 15158476
TI  - Use of protein-acrylamide copolymer hydrogels for measuring protein concentration
      and activity.
AB  - We report the development and characterization of a polyacrylamide-based protein
      immobilization strategy for surface-bound protein assays, including concentration
      detection, binding affinity, and enzyme kinetics. Glutathione S-transferase (GST)
      fusion proteins have been labeled with an acrylic moiety and attached to acrylic
      functionalized glass surfaces through copolymerization with acrylic monomer. The
      specific attachment of GST-green fluorescent protein (GFP) fusion protein was
      more than sevenfold greater than the nonspecific attachment of nonacrylic-labeled
      GST-GFP; 0.32 ng/mm(2) of surface-attached GST-GFP was detectable by direct
      measurement of GFP fluorescence and this lower detection limit was reduced to
      0.080 ng/mm(2) using indirect antibody-based detection. The polyacrylamide-based
      surface attachment strategy was also used to measure the kinetics of substrate
      phosphorylation by the kinase c-Src. Michaelis-Menten kinetic constants for the
      reaction occurring in solution were K(m) = 2.7 +/- 1.0 microM and V(max) = 8.1 +/
      3.1 (arbitrary units). Kinetic values for the reaction utilizing surface
      immobilized substrate were K(m) = 0.36 +/- 0.033 microM and V(max) = 9.7 +/- 0.63
      and were found to be independent of the acrylamide concentration within the
      copolymer. Such a surface attachment strategy should be applicable to the
      proteomics field and addresses denaturation and dehydration problems associated
      with protein microarray development.

PMID- 15158477
TI  - Dual-polarization interferometry: an analytical technique to measure changes in
      protein structure in real time, to determine the stoichiometry of binding events,
      and to differentiate between specific and nonspecific interactions.
AB  - The study of solution-phase interactions between small molecules and immobilized
      proteins is of intense interest, especially to the pharmaceutical industry. An
      optical sensing technique, dual polarization interferometry, has been employed
      for the detailed study of a model protein system, namely, d-biotin interactions
      with streptavidin immobilized on a solid surface. Changes in thickness and
      density of an immobilized streptavidin layer as a result of the binding of d
      biotin have been directly measured in solution and in real time. The results
      obtained from this approach are in excellent agreement with X-ray
      crystallographic data for the structural changes expected in the streptavidin-D
      biotin system. The mass changes measured on binding d-biotin also agree closely
      with anticipated binding capacity values. Determination of the density changes
      occurring in the protein adlayer provides a means for differentiation between
      specific and nonspecific interactions.

PMID- 15158478
TI  - Quantitative gas chromatography/mass spectrometry determination of C
      mannosylation of tryptophan residues in glycoproteins.
AB  - C-mannosylation of Trp residue is one of the most recently discovered types of
      glycosylation, but the identification of these mannosylated residues in proteins
      is rather tedious. In a previous paper, it was reported that the complete
      analysis of all constituents of glycoproteins (sialic acids, monosaccharides, and
      amino acids) could be determined on the same sample in three different steps of
      gas chromatography/mass spectrometry of heptafluorobutyrate derivatives. It was
      observed that during the acid-catalyzed methanolysis step used for liberation of
      monosaccharide from classical O- and N-glycans, Trp and His were quantitatively
      transformed by the addition of a methanol molecule on their indole and imidazole
      groups, respectively. These derivatives were stable to acid hydrolysis used for
      the liberation of amino acids. Since monosaccharide derivatives were also
      stabilized as heptafluorobutyrate derivatives of O-methyl-glycosides, it was
      suggested that C-mannosides of Trp residues could quantitatively be recovered.
      Based on the analyses of standard compounds, peptides and RNase 2 from human
      urine, we report that C((2))-mannosylated Trp could be quantitatively recovered
      and identified during the step of amino acid analysis. Analyses of different
      samples indicated that this type of glycosylation is absent in bacteria and
      yeasts.

PMID- 15158479
TI  - Chloroplast biogenesis 89: development of analytical tools for probing the
      biosynthetic topography of photosynthetic membranes by determination of resonance
      excitation energy transfer distances separating metabolic tetrapyrrole donors
      from chlorophyll a acceptors.
AB  - The thorough understanding of photosynthetic membrane assembly requires a deeper
      knowledge of the coordination and regulation of the chlorophyll (Chl) and
      thylakoid apoprotein biosynthetic pathways. As a working hypothesis we have
      recently proposed three different Chl-thylakoid apoprotein biosynthesis models: a
      single-branched Chl biosynthetic pathway (SBP)-single location model, a SBP
      multilocation model, and a multibranched Chl biosynthetic pathway (MBP)
      sublocation model. The detection of resonance excitation energy transfer between
      tetrapyrrole precursors of Chl, and several Chl-protein complexes, has made it
      possible to test the validity of the proposed Chl-thylakoid apoprotein
      biosynthesis models by resonance excitation energy transfer determinations. In
      this work, resonance excitation energy transfer techniques that allow the
      determination of distances separating tetrapyrrole donors from Chl-protein
      acceptors in green plants by using readily available electronic spectroscopic
      instrumentation are developed. It is concluded that the calculated distances are
      compatible with the MBP-sublocation model and incompatible with the operation of
      the SBP-single location Chl-protein biosynthesis model.

PMID- 15158480
TI  - A multiplexing single nucleotide polymorphism typing method based on restriction
      enzyme-mediated single-base extension and capillary electrophoresis.
AB  - Millions of single nucleotide polymorphisms (SNPs) have been identified in recent
      years. This provides a great opportunity for large-scale association and
      population studies. However, many high-throughput SNP typing techniques require
      expensive and dedicated instruments, which render them out of reach for many
      laboratories. To meet the need of these laboratories, we here report a method
      that uses widely available DNA sequencer for SNP typing. This method uses a type
      II restriction enzyme to create extendable ends at target polymorphic sites and
      uses single-base extension (SBE) to discriminate alleles. In this design, a
      restriction site is engineered in one of the two polymerase chain reaction (PCR)
      primers so that the restriction endonuclease cuts immediately upstream of the
      targeted SNP site. The digestion of the PCR products generates a 5'-overhang
      structure at the targeted polymorphic site. This 5'-overhang structure then
      serves as a template for SBE reaction to generate allele-specific products using
      fluorescent dye-terminator nucleotides. Following the SBE, the allele-specific
      products with different sizes can be resolved by DNA sequencers. Through primer
      design, we can create a series of PCR products that vary in size and contain only
      one restriction enzyme recognition site. This allows us to load many PCR products
      in a single capillary/lane. This method, restriction-enzyme-mediated single-base
      extension, is demonstrated by typing multiple SNPs simultaneously for 44 DNA
      samples. By multiplexing PCR and pooling multiplexed reactions together, this
      method has the potential to score 50-100 SNPs/capillary/run if the sizes of PCR
      products are arranged at every 5-10 bases from 100 to 600 base range.

PMID- 15158481
TI  - Monitoring for dynamic biological processing by intramolecular bioluminescence
      resonance energy transfer system using secreted luciferase.
AB  - Proteolytic processing plays crucial roles in physiological and
      pathophysiological cellular functions such as peptide generation, cell cycle, and
      apoptosis. We developed a novel biophysical bioluminescence resonance energy
      transfer (BRET) system between a secreted Vargula luciferase (Vluc) and an
      enhanced yellow fluorescent protein (EYFP) for visualization of cell biological
      processes. The bioluminescence spectrum of the fusion protein (Vluc-EYFP) is
      bimodal (lambdamax = 460 nm (Vluc) and 525nm (EYFP)), indicating that the excited
      state energy of Vluc transfers to EYFP (in short, BRET). The BRET signal can be
      measured in the culture medium and pursue quantitative production of two
      neuropeptides, nocistatin (NST) and nociceptin/orphanin FQ (N/OFQ) in living
      cells. NST and N/OFQ are located in tandem on the same precursor, but NST
      exhibits antagonistic action against N/OFQ-induced central functions. Insertion
      of a portion of the NST-N/OFQ precursor (Glu-Gln-Lys-Gln-Leu-Gln-Lys-Arg-Phe-Gly
      Gly-Phe-Tyr-Gly) in Vluc-EYFP makes the fusion protein cleavable at Lys-Arg in
      NG108-15 cells, and proprotein convertase 1 enhances this digestion. The change
      in BRET signals quantifies the processing of the fusion protein. Our novel
      intramolecular BRET system using a secreted luciferase is useful for
      investigating peptide processing in living cells.

PMID- 15158482
TI  - Electron microscopy as a quantitative method for investigating tau
      fibrillization.
AB  - Fibrillization of tau protein is a hallmark lesion in Alzheimer's disease. To
      clarify the utility of electron microscopy as a quantitative assay for tau
      fibrillization in vitro, the interaction between synthetic tau filaments and
      carbon/formvar-coated grids was characterized in detail. Filament adsorption onto
      grids was hyperbolic when analyzed as a function of time or bulk protein
      concentration, with no evidence for competitive displacement or elution from
      other components in the reaction mixture. Filament length measurements were
      linear with filament concentration so long as the concentration of total tau
      protein in the sample was held constant, suggesting that measurement of filament
      lengths was accurate under these conditions. Furthermore, exponential filament
      length distributions were not significantly affected by adsorption time or
      filament concentration, suggesting that preferential binding among filaments of
      differing lengths was minimal. However, monomeric tau protein was found to be a
      strong competitor of filament adsorption, indicating that comparison of filament
      length measurements at different bulk tau concentrations should be interpreted
      with caution.

PMID- 15158483
TI  - Carbon nanotube aqueous sol-gel composites: enzyme-friendly platforms for the
      development of stable biosensors.
AB  - A new type of composite material based on carbon nanotubes and an aqueous sol-gel
      process has been developed. The electrochemical characteristics of these
      composites were investigated and compared to composites made with an alkoxy
      silane sol-gel process. The use of carbon nanotubes, as the conductive part of
      the composite, facilitated fast electron transfer rates. The feasibility of this
      type of composite for the development of biosensors was demonstrated using l
      amino acid oxidase. The stability of the enzyme was increased when it was
      encapsulated in the aqueous sol-gel, and the sensor retained more that 50% of its
      response after 1 month of testing.

PMID- 15158484
TI  - Cell surface detection of membrane protein interaction with homogeneous time
      resolved fluorescence resonance energy transfer technology.
AB  - Direct or indirect interactions between membrane proteins at the cell surface
      play a central role in numerous cell processes, including possible synergistic
      effects between different types of receptors. Here we describe a method and tools
      to analyze membrane protein-protein interaction at the surface of living cells.
      This technology is based on the use of specific antibodies directed against each
      partner and labeled either with europium cryptate or with Alexa Fluor 647. This
      allows the measurement of a fluorescence resonance energy transfer (FRET) signal
      in a time-resolved manner if both antibodies are in close proximity. This
      approach is here validated using the heterodimeric gamma-aminobutyrate B receptor
      as a model. We show that after washing out the unbound antibodies, the time
      resolved FRET signal can be measured together with the expression level of both
      partners via the quantification of the donor and the acceptor fluorophores bound
      to the cells. Thanks to the high sensitivity of this method and to the low
      concentration of antibodies required, we show that the signal can also be
      measured directly after the incubation period without washing out the unbound
      antibody (homogeneous time-resolved FRET). As such, this method is highly
      sensitive, reproducible, and compatible with the development of high-throughput
      screening protocols.

PMID- 15158485
TI  - Assay method for Escherichia coli photolyase activity using single-strand cis-syn
      cyclobutane pyrimidine dimer DNA as substrate.
AB  - A high-performance liquid chromatography method for the assay of Escherichia coli
      photolyase activity was developed. When cis-syn cyclobutane pyrimidine dimer was
      used as substrate, the Michaelis constant (K(m)) value for the photolyase
      activity was 100 nM. The linear range of the calibration curve of the photolyase
      activity was 0.026-6.64 microU/assay tube. The correlation coefficient for this
      linearity was 0.998. The limit of detection (S/N = 3) was 26 nU/assay tube. The
      photolyase activity was increased 1.6-fold in the presence of 5,10
      methenyltetrahydrofolic acid in the enzyme reaction mixture.

PMID- 15158486
TI  - Kinetic measurements of phosphoglucomutase by direct analysis of glucose-1
      phosphate and glucose-6-phosphate using ion/molecule reactions and Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - A method for the direct determination of kinetic constants for phosphoglucomutase
      and its phosphorylated products is described. Fourier transform ion cyclotron
      resonance gas-phase ion/molecule reactions between trimethyl borate and glucose
      phosphate, phosphorylated at either the 1 or the 6 position, generate mass
      spectra distinguishable with regard to product ion distribution. A multicomponent
      quantification method is utilized to determine the composition of a binary
      mixture of the two positional isomers. Using this method, the conversion between
      glucose-1-phosphate and glucose-6-phosphate can be directly monitored without the
      use of coupling enzymes. The values of K(m) for glucose-1-phosphate and glucose-6
      phosphate were determined using the substrate-velocity plot and the Haldane
      relationship, respectively. Values of V(max) for both the forward and the reverse
      directions were measured, and the equilibrium constant for the reversible
      reaction was determined using this methodology. Kinetic parameters measured
      correlate well with those obtained using traditional methods. The assay was
      demonstrated to be accurate and particularly convenient to determine kinetic
      constants for enzymatic systems that involve the interconversion of
      phosphorylated positional isomers.

PMID- 15158488
TI  - Construction of a full-length human T cell leukemia virus type I genome from MT-2
      cells containing multiple defective proviruses using overlapping polymerase chain
      reaction.
AB  - Human T cell leukemia virus type I (HTLV-I), the etiological agent of adult T
      cell leukemia, integrates into the host genome as a provirus. Multiple defective
      copies of the integrated provirus are often present in the host genome. For this
      reason it is difficult to clone the intact provirus from HTLV-I-infected cells
      using conventional techniques. Here, we used overlapping polymerase chain
      reaction (PCR) to construct a full-length provirus of HTLV-I directly from an
      HTLV-I-transformed cell line, MT-2, which contains multiple defective proviruses.
      First, four overlapping proviral HTLV-I fragments (1.4-3.9 kb each) were
      constructed from genomic MT-2 DNA using PCR. Next, the complete HTLV-I proviral
      DNA (9 kb) was generated from these fragments using asymmetric PCR and cloned
      into a plasmid vector. 293 T cells transfected with this plasmid produced virus
      like particles, and we show that these particles are capable of infecting a human
      T cell line. We propose that this cloning technique constitutes a powerful tool
      for constructing infectious molecular clones from cells of patients infected with
      HTLV-I or other viruses.

PMID- 15158487
TI  - A high-affinity reversible protein stain for Western blots.
AB  - We describe a reversible staining technique, using MemCode, a reversible protein
      stain by which proteins can be visualized on nitrocellulose and polyvinylidine
      fluoride (PVDF) membranes without being permanently fixed to the membrane itself.
      This allows subsequent immunoblot analysis of the proteins to be performed. The
      procedure is applicable only to protein blots on nitrocellulose and PVDF
      membranes. MemCode is a reversible protein stain composed of copper as a part of
      an organic complex that interacts noncovalently with proteins. MemCode shows
      rapid protein staining, taking 30s to 1 min for completion. The method is simple
      and utilizes convenient application conditions that are compatible with the
      matrix materials and the protein. The stain is more sensitive than any previously
      described dye-based universal protein staining system. The turquoise-blue-stained
      protein bands do not fade with time and are easy to photograph compared to those
      stained with Ponceau S. Absorbance in the blue region of the spectrum offers good
      properties for photo documentation and avoids interference from common biological
      chromophores. The stain on the protein is easily reversible in 2 min for
      nitrocellulose membrane and in 10 min for PVDF membrane with MemCode stain
      eraser. The stain is compatible with general Western blot detection systems, and
      membrane treatment with MemCode stain does not interfere with conventional
      chemiluminescent or chromogenic detection using horseradish peroxide and alkaline
      phosphatase substrates. The stain is also compatible with N-terminal sequence
      analysis of proteins.

PMID- 15158490
TI  - Approach for defining endogenous reference genes in gene expression experiments.
AB  - The quantification of gene expression by real-time polymerase chain reaction
      (PCR) has revolutionized the field of gene expression analysis. Due to its
      sensitivity and flexibility it is becoming the method of choice for many
      investigators. However, good normalization protocols still have to be implemented
      to facilitate data exchange and comparison. We have designed primers for 10
      unrelated genes and developed a simple protocol to detect genes with stable
      expression that are suitable for use as endogenous reference genes for further
      use in the normalization of gene expression data obtained by real-time PCR. Using
      this protocol, we were able to identify human proteosome subunit Y as a reliable
      endogenous reference gene for human umbilical vein endothelial cells treated for
      up to 18 h with TNFalpha, IL-4, or IFNgamma and for B cells isolated from healthy
      controls and patients suffering from IgA nephropathy. Other optional endogenous
      reference genes that can be considered are phosphomannomutase (PPMM) and actin
      for endothelial cells and glyceraldehyde-3-phosphate dehydrogenase and PPMM for B
      cells.

PMID- 15158491
TI  - Origin of the anomalous circular dichroism spectra of many apomyoglobin mutants.
AB  - Several authors have reported that many sperm whale apomyoglobin mutants show
      anomalous circular dichroism spectra. These mutants have a low molar ellipticity
      compared to the wild-type protein but in several cases have the same stability of
      unfolding. A model in which native apomyoglobin is not folded in the same manner
      as that in other proteins and in which mutants show progressive reductions in
      their degree of folding has been suggested to explain this phenomenon. However,
      nuclear magnetic resonance of the native apomyoglobin conformation has shown that
      this state is folded and compact, raising the possibility that the anomalous
      circular dichroism spectra could have another explanation. We studied several
      mutants with anomalous circular dichroism spectra and found that these proteins
      were all contaminated with nucleic acid that contributed to the ultraviolet
      absorption and caused uncertainty in the determination of protein concentration.
      The resulting overestimation of the concentration of apomyoglobin explains the
      phenomenon of anomalous circular dichroism spectra. We describe a procedure to
      remove the contaminant nucleic acid which yields accurate protein concentration
      measurements and provides the normal circular dichroism spectra. Our findings
      support a well-structured native conformation for apomyoglobin and may also be of
      the interest to scientists working with the purification of recombinant proteins.

PMID- 15158489
TI  - A proteomic approach to identify phosphoproteins encoded by cDNA libraries.
AB  - We report a method for large-scale rapid analysis of phosphoproteins in tissues
      or cells by combining immobilized metal affinity chromatography (IMAC) with phage
      display cDNA library screening. We expressed a testis cDNA library as fusion
      proteins on phage and, using IMAC, enriched for sequences encoding
      phosphoproteins. Selected clones were polymerase chain reaction amplified and
      sequenced. The majority of the clones sequenced (80%) encoded known proteins
      previously identified as phosphoproteins. Immunoblotting with phosphotyrosine
      antibodies confirmed that some of the selected sequences encoded tyrosine
      phosphorylated proteins when expressed on phage. An advantage of this method is
      the rapid identification of phosphoproteins encoded by a cDNA library, which can
      identify proteins that are potentially phosphorylated in vivo. When this method
      is combined with limited enzymatic digestion and tandem mass spectrometric
      techniques, the specific phosphorylation site in a protein can be identified.
      This technique can be used in proteomics studies to effectively detect
      phosphorylated proteins and avoid time-consuming and expensive peptide
      sequencing.

PMID- 15158492
TI  - Importance of product/reactant equilibration in the kinetics of the
      phosphoglucose isomerization reaction by differential stopped flow
      microcalorimetry.
AB  - The kinetics for the isomerization of fructose-6-phosphate to glucose-6-phosphate
      (F6P --> G6P) by baker's yeast phosphoglucose isomerase (PGI) with regard to
      k(cat) and K(m) were determined from analysis of differential stopped flow
      microcalorimeter measurements using the integrated form of the Michaelis-Menten
      rate equation. Values for K(m) (F6P --> G6P) that were determined at pH 8.0 and
      ionic strength 0.1M at 293.4, 298.4, 303.4, and 311.5K exhibited a linear
      dependence on the substrate concentration at each temperature because of the
      substrate-product equilibrium. The minimum values for K(m) ranged from 2.62+/
      0.55 mM at 293.4K to 7.8+/-4.8mM at 311.5K and were the same as the minimum
      values for the reverse reaction (G6P --> F6P) at 293.4 K and 298.4 K. Minimum
      values for k(cat) increased with temperature, from 2.78+/-0.34s(-1) at 293.4K to
      11.4+/-1.0s(-1) at 311.5K, and for the reverse reaction, G6P --> F6P, from
      0.852+/-0.086 s(-1) at 293.4K to 1.46+/-0.06s(-1) at 298.4K. The enzyme
      efficiency at 311.5K is close to the collision rate for a diffusion-controlled
      process in solution. The [F6P]/[G6P] equilibrium constants were determined from
      comparison of the values of k(cat) in both directions and were 0.307+/-0.053 at
      293.4K and 0.395+/-0.033 at 298.4K. The heats of reaction in the F6P --> G6P
      direction increased from -8.96+/-0.26 kJmol(-1) at 311.5K to -8.27+/-0.40 kJmol(
      1) at 293.4K, a value in fair agreement with 7.01+/-0.32 kJmol(-1) in the
      opposite G6P --> F6P direction.

PMID- 15158494
TI  - Determination of endogenous and supplied deuterated abscisic acid in plant
      tissues by high-performance liquid chromatography-electrospray ionization tandem
      mass spectrometry with multiple reaction monitoring.
AB  - A specific, sensitive, and accurate method for determination of abscisic acid
      (ABA) in plant tissues is described. The method employs reversed-phase high
      performance liquid chromatography and electrospray ionization-tandem mass
      spectrometry for multiple reaction monitoring of underivatized ABA and deuterated
      ABA analogs. Specific analogs were used to study the mechanism of ABA
      fragmentation, to select appropriate standards, and to identify compounds
      suitable for metabolic studies involving the supply of differentially labeled
      ABA. Limits of detection and quantification of 1.9 and 4.7 pg, respectively, were
      obtained over a linear calibration range of 0-1.5 ng ABA (on-column injected)
      using 5.8', 8', 8'-d(4) ABA as the internal standard. Accuracy and precision were
      within 15% for routine quality control samples. The method of standard additions,
      as applied to Arabidopsis thaliana seed extracts, was also used to validate the
      method for analysis of plant tissue samples. The utility of the method was
      further demonstrated by determining levels of ABA in western white pine seeds and
      of ABA and supplied 8', 8', 8', 9', 9', 9'-d(6) ABA in Brassica napus tissues,
      using 5.8', 8', 8'-d(4) ABA or 8', 8', 8'-d(3) ABA as the internal standard.
      Limits of quantification as low as 0.89 ng/g were achieved by optimizing the
      extraction procedure for each type of plant tissue.

PMID- 15158493
TI  - Analysis of small-molecule interactions using Biacore S51 technology.
AB  - Biacore S51 is a new surface plasmon resonance-based biosensor developed by
      Biacore AB (Uppsala, Sweden). The instrument was engineered specifically to
      support small-molecule drug discovery and development. The platform includes
      increased sensitivity, larger sample handling capabilities, and automated data
      processing to improve throughput. Compared to previously released Biacore
      instruments, the most significant design change relates to the introduction of
      the hydrodynamic-addressing flow cell. This design allows two reaction surfaces
      and a reference surface to be placed within the same flow cell, thereby improving
      data quality and extending the kinetic range of the instrument. Using a set of
      small-molecule inhibitors of the enzyme carbonic anhydrase II, we tested the
      reproducibility, sensitivity, and dynamic range of the biosensor. Given the S51's
      performance capabilities, it should play an active role in secondary screening by
      providing high-resolution information for small-molecule/target interactions.

PMID- 15158496
TI  - Using multiplexed real-time polymerase chain reaction to rapidly identify single
      copy transgenic animals.

PMID- 15158495
TI  - Delaying photobleaching and recovering luminescence of a DNA molecular light
      switch in DNA analysis.

PMID- 15158498
TI  - A method for removing ethylenediaminetetraacetic acid from apo-proteins.

PMID- 15158497
TI  - Chemiluminescence from the Sakaguchi reaction.

PMID- 15158500
TI  - Manipulation of intracellular pH by electroporation: an alternative method for
      fast calibration of pH in living cells.

PMID- 15158499
TI  - Escherichia coli methionine aminopeptidase with Tyr168 to alanine substitution
      can improve the N-terminal processing of recombinant proteins with valine at the
      penultimate position.

PMID- 15158501
TI  - Decolorization of synthetic dyes by solid state cultures of Lentinula (Lentinus)
      edodes producing manganese peroxidase as the main ligninolytic enzyme.
AB  - The ability of the white-rot fungus Lentinula (Lentinus) edodes to decolorize
      several synthetic dyes was investigated using solid state cultures with corn cob
      as substrate. Cultures, containing amido black, congo red, trypan blue, methyl
      green, remazol brilliant blue R, methyl violet, ethyl violet and Poly R478 at 200
      ppm, were completely decolorized after 18 days of incubation. Partial
      decolorization was observed in the cultures containing 200 ppm of brilliant
      cresyl blue and methylene blue. High manganese peroxidase activity (2600 U/g
      substrate), but very low lignin peroxidase (<10 U/g substrate) and laccase (<16
      U/g substrate) activities were detected in the cultures. In vitro, the dye
      decolorization was markedly decreased by the absence of manganic ions and H2O2.
      These data suggest that manganese peroxidase appear to be the main responsible
      for the capability of L. edodes to decolorize synthetic dyes.

PMID- 15158502
TI  - Batch biological treatment of nitrogen deficient synthetic wastewater using
      Azotobacter supplemented activated sludge.
AB  - Biological treatment of nitrogen deficient wastewaters are usually accomplished
      by external addition of nitrogen sources to the wastewater which is an extra cost
      item. As an alternative for effective biological treatment of nitrogen deficient
      wastewaters, the nitrogen fixing bacterium, Azotobacter vinelandii, was used in
      activated sludge and also in pure culture. Total organic carbon (TOC) removal
      performances of Azotobacter-added and free activated sludge cultures were
      compared at different initial TN/TOC ratios. The rate and extent of TOC removal
      were comparable for all cultures when initial TN/TOC ratio was larger than 0.12;
      however, both the rate and extent of TOC removal from nitrogen deficient
      (TN/TOC<12%) synthetic wastewater were improved by using Azotobacter-added
      activated sludge as compared to the Azotobacter-free activated sludge culture.
      More than 90% TOC removal was obtained with pure Azotobacter or Azotobacter-added
      activated sludge culture from a nitrogen deficient synthetic wastewater.

PMID- 15158503
TI  - Coliform concentration reduction and related performance evaluation of a down
      flow anaerobic fixed bed reactor treating low-strength saline wastewater.
AB  - Low-strength saline wastewater may be generated by tourist facilities, industries
      and communities located in coastal areas. Sea salts, mostly chlorides, when
      present in wastewaters at high concentrations, can cause inhibition on biological
      treatment processes. In this study, a laboratory down-flow anaerobic fixed bed
      reactor (DFAFBR) was used for treating saline wastewater. This wastewater was
      simulated by dilution of piggery manure in a synthetic saline water to obtain a
      final total COD concentration in the range of 1100-2900 mg/l and a salt
      concentration of 15 g/l. The DFAFBR was operated at hydraulic retention times
      (HRT) of 96, 48, 24 and 12 h. The results showed that at sea salts concentrations
      in the range from 5 to 15 g/l, total coliform concentration reduction
      efficiencies higher than 97% were achieved. A decrease in the total and faecal
      coliform concentration reduction efficiencies from 99.5% to 90.5% and 92.5%,
      respectively, was observed when the HRT decreased from 96 to 12 h. Enumeration of
      coliform bacteria isolated from the biofilm in different zones of the reactor
      showed that more than 94% of the total amount was removed in the upper zone. A
      HRT of 24 h was required to obtain total COD, organic-N, total-P and faecal
      coliform concentration reduction efficiencies higher than 72%, 51%, 39% and 98%,
      respectively. A concentration of 8.4 g/l for chlorides, 1.25 g/l for sulphates
      and 4.6 g/l for sodium did not affect the process performance.

PMID- 15158505
TI  - Survival and viability of Ascaris suum and Oesophagostomum dentatum in ensiled
      swine faeces.
AB  - The survival and viability of eggs from Ascaris suum and Oesophagostomum dentatum
      and of infective larvae (L3) from O. dentatum were determined in the ensiled
      solid fraction of swine faeces after 0, 7, 14, 28 and 56 days of ensiling. The
      experiment had two treatments, un-ensiled and ensiled manure, in a split-plot
      design. Each of 50 containers was inoculated with 40,000 eggs of both A. suum and
      O. dentatum, and another 50 containers were inoculated with 32,747 L3 of O.
      dentatum each. A. suum eggs were not destroyed by the ensiling process, although
      their viability was diminished. O. dentatum eggs and larvae were destroyed during
      the first 7-14 days of the ensiling process.

PMID- 15158504
TI  - Pecan shell-based granular activated carbon for treatment of chemical oxygen
      demand (COD) in municipal wastewater.
AB  - The present investigation was undertaken to compare the adsorption efficiency of
      pecan shell-based granular activated carbon with the adsorption efficiency of the
      commercial carbon Filtrasorb 200 with respect to uptake of the organic components
      responsible for the chemical oxygen demand (COD) of municipal wastewater.
      Adsorption efficiencies for these two sets of carbons (experimental and
      commercial) were analyzed by the Freundlich adsorption model. The results
      indicate that steam-activated and acid-activated pecan shell-based carbons had
      higher adsorption for organic matter measured as COD, than carbon dioxide
      activated pecan shell-based carbon or Filtrasorb 200 at all the carbon dosages
      used during the experiment. The higher adsorption may be related to surface area
      as the two carbons with the highest surface area also had the highest organic
      matter adsorption. These results show that granular activated carbons made from
      agricultural waste (pecan shells) can be used with greater effectiveness for
      organic matter removal from municipal wastewater than a coal-based commercial
      carbon.

PMID- 15158506
TI  - Anaerobic biodegradation of no. 2 diesel fuel in soil: a soil column study.
AB  - Soil and sediments are contaminated with petroleum hydrocarbons in many parts of
      the world. Anaerobic degradation of petroleum hydrocarbon is very relevant in
      removing oil spills in the anaerobic zones of soil and sediments. This research
      investigates the possibility of degrading no. diesel fuel under anaerobic
      conditions. Anaerobic packed soil columns were used to simulate and study in situ
      bioremediation of soil contaminated with diesel fuel. Several anaerobic
      conditions were evaluated in soil columns, including sulfate reducing, nitrate
      reducing, methanogenic, and mixed electron acceptor conditions. The objectives
      were to determine the extent of diesel fuel degradation in soil columns under
      various anaerobic conditions and identify the best conditions for efficient
      removal of diesel fuel. Diesel fuels were degraded significantly under all
      conditions compared to no electron supplemented soil column (natural
      attenuation). However, the rate of diesel degradation was the highest under mixed
      electron acceptor conditions followed in order by sulfate reducing, nitrate
      reducing, and methanogenic conditions. Under mixed electron acceptor condition
      81% of diesel fuel was degraded within 310 days. While under sulfate reducing
      condition 54.5% degradation of diesel fuel was observed for the same period. This
      study showed evidence for diesel fuel metabolism in a mixed microbial population
      system similar to any contaminated field sites, where heterogeneous microbial
      population exists.

PMID- 15158507
TI  - Subcellular localization of copper in the root cells of Allium sativum by
      electron energy loss spectroscopy (EELS).
AB  - Ultrastructural investigation of the root cells of Allium sativum L. exposed to
      three different concentrations of Cu (1, 10 and 100 microM) for 9 days was
      carried out using transmission electron microscopy (TEM) and electron energy loss
      spectroscopy (EELS). The results presented here indicate that excess Cu induces
      ultrastructural changes such as strong vacuolization, condensed nuclear
      chromatin, decreased endoplasmic reticulum (ER) and ribosome and serious
      plasmolysis. EELS analysis indicated that electron dense granules containing Cu
      appeared in the cells after Cu treatment. The vacuoles of the root tip cells were
      the main Cu-accumulation site. Small amounts of copper were also localized to
      cytoplasmic vesicles or cell walls of cortical cells. The results of the present
      investigation have significant importance in further understanding the mechanisms
      of absorption, transportation and accumulation of heavy metals in plants grown in
      polluted soil.

PMID- 15158508
TI  - Carbon, nitrogen and phosphorus mineralization in two soils amended with
      distillery yeast.
AB  - The possibility of using yeast from alcohol distilleries as a source of nutrients
      in soil was investigated. The following treatments were used: no fertilization
      (control), 0.5% (w/w) yeast, 1% (w/w) yeast, and NPK. The decomposition of yeast
      was monitored for 90 days in two soils. The CO2 production and the microbial
      biomass were increased by an average of 1- to 3-fold by yeast incorporation
      compared to control. Protease activity also was enhanced 3- to 8-fold in the
      soils supplemented with yeast compared to control. The phosphatase activities
      were higher than control only during the first days. While nitrate contents
      increased in all treatments compared to control, available P only increased in
      the soils amended with 1% yeast or NPK by 45-119% and 309-489%, respectively.
      These results indicate that there exists an excellent potential for the use of
      yeast in the soil as a source of nitrate and available P for plant nutrition.

PMID- 15158510
TI  - UV spectroscopy: a tool for monitoring humification and for proposing an index of
      the maturity of compost.
AB  - Composting organic matter is an interesting way to valorize waste. Compost is a
      product obtained after a humification process. The humification of organic matter
      during composting was studied by the quantification and monitoring of the
      evolution of humic substances. The final objective was to be able to evaluate the
      state of humification based on a spectrum of total humic substances using the
      method of UV spectral deconvolution. This study presented a new index obtained by
      UV spectroscopy using the deconvolution of an unknown spectrum of compost with 3
      reference spectra. This index was compared to the maturity indices usually used,
      such as total extraction of humic substances (rate of extraction), IP (index of
      polymerization) or the humic acid to fulvic acid ratio. This new parameter, which
      was easy and quick to determine, gave precise information about the quality of
      the compost. It made it possible to disregard the values of aberrant
      concentrations caused by the classical protocol of extraction. Compared to the
      humic acid to fulvic acid ratio, the new index obtained by UV spectral
      deconvolution showed more representative results: the humic acid to fulvic acid
      ratio for an apparently non-mature compost was abnormally high, suggesting that
      the compost was mature, whereas the UV index proposed showed that the compost was
      really young and not yet humified.

PMID- 15158509
TI  - Evaluation of Argentinean white rot fungi for their ability to produce lignin
      modifying enzymes and decolorize industrial dyes.
AB  - The decolorizing capacity of 26 white rot fungi from Argentina was investigated.
      Extracellular production of ligninolytic enzymes by mycelium growing on solid
      malt extract/glucose medium supplemented with different dyes (Malachite Green,
      Azure B, Poly R-478, Anthraquinone Blue, Congo Red and Xylidine), dye
      decolorization and the relationship between these two processes were studied.
      Only ten strains decolorized all the dyes, all ten strains produced laccase,
      lignin peroxidase and manganese peroxidase on solid medium. However, six of the
      strains could not decolorize any of the dyes; all six strains tested negative for
      lignin peroxidase, and produced less than 0.05 U/g agar of manganese peroxidase.
      Comparing the isolates with the well-known dye-degrader Phanerochaete
      chrysosporium, a new fungus was identified: Coriolus versicolor f. antarcticus,
      potentially a candidate for use in biodecoloration processes. Eighteen day-old
      cultures of this fungus were able to decolorize in an hour 28%, 30%, 43%, 88% and
      98% of Xylidine (24 mg/l), Poly R-478 (75 mg/l), Remazol Brilliant Blue R (9
      mg/l), Malachite Green (6 mg/l) and Indigo Carmine (23 mg/l), respectively.
      Laccase activity was 0.13 U/ml, but neither lignin peroxidase nor manganese
      peroxidase were detected in the extracellular fluids for that day of incubation.

PMID- 15158511
TI  - A test of four plant species to reduce total nitrogen and total phosphorus from
      soil leachate in subsurface wetland microcosms.
AB  - Four wetland plant species (Scirpus validus, Carex lacustris, Phalaris
      arundinacea, and Typha latifolia) were grown in monoculture and as a four-species
      mixture to compare effectiveness of nutrient removal in controlled 18.93-l
      outdoor subsurface treatment wetland microcosms. A nutrient treatment that
      mimicked single-resident domestic effluent consisted of two levels of nitrogen
      (N) and phosphorus (P) [low (56 mg/l N and 31 mg/l P) and high (112 mg/l N and 62
      mg/l P)] of nutrient solution applied three times weekly. The plants were
      established and maintained for one year before the nutrient treatment and monthly
      water sampling commenced; water sampling began July 31, 2001 and ended October
      23, 2001. We tested four hypotheses: (1) vegetated microcosms are more effective
      at reducing concentrations of total N and total P from soil leachate than
      unvegetated, (2) there is a differential species effect on the potential to
      reduce N and P, (3) plant mixtures are more effective than monocultures at
      reducing N and P, and (4) the microcosms will be least effective at reducing N
      and P concentrations in October compared to August. We found support for
      hypotheses 1, 2, and 4, but our results are inconclusive for the third
      hypothesis. Total N and total P in the soil leachate were significantly higher
      from unvegetated microcosms compared to vegetated. S. validus was most effective
      and P. arundinacea was generally least effective at reducing N and P in
      monocultures, with treatment capabilities similar to unvegetated microcosms. The
      four-species mixture was generally highly effective at nutrient removal, however
      the results were not significantly different from the monocultures. At the end of
      the growing season (October) treatment efficiency was significantly less than
      earlier months, especially for the unvegetated treatment.

PMID- 15158513
TI  - Performance of a fixed-bed reactor packed with carbon felt during anaerobic
      digestion of cellulose.
AB  - The anaerobic digestion of cellulose was assessed in batch and semi-continuous
      studies using a carbon felt fixed-bed reactor. In the batch operation, the
      volatile solids reduction (%) and the cumulative methane production during the
      mesophilic and thermophilic digestion were 52.2% and 15.9%, 96.7 and 49.2 ml/g
      total solid fed, respectively. After 99 days of semi-continuous mesophilic
      digestion, the degradation of cellulose reached its highest level of 67.6% at the
      hydraulic retention time of 9 days. The methane production and methane
      concentration of biogas from the bioreactor were maintained at a steady state.
      The fixed-bed reactor with carbon felt would be suitable for the efficient
      anaerobic digestion of cellulose. The biomass distribution in the reactor was, in
      the liquid phase 0.73 g/l-reactor, in the felt 1.59 g/l-reactor, and on the felt
      surface 9.86 g/l-reactor, which indicated that most of the microbes were
      immobilized on the carbon felt fixed-bed in the reactor.

PMID- 15158512
TI  - Biosorption of uranium by lake-harvested biomass from a cyanobacterium bloom.
AB  - The aim of this work was to study some basic aspects of uranium biosorption by
      powdered biomass of lake-harvested cyanobacterium water-bloom, which consisted
      predominantly of Microcystis aeruginosa. The optimum pH for uranium biosorption
      was between 4.0 and 8.0. The batch sorption reached the equilibrium within 1 h.
      The isotherm fitted the Freundlich model well. Although the Langmuir model fitted
      the experiment data well at pH 3.0, 5.0 and 7.0, it did not fit at pH 9.0 and
      11.0 at all. This implies that different biosorption mechanisms may be involved
      at different pH values. 0.1 N HCl was effective in uranium desorption. The
      results indicated that the naturally abundant biomass of otherwise nuisance
      cyanobacterium bloom exhibited good potential for application in removal of
      uranium from aqueous solution.

PMID- 15158514
TI  - Dynamics of biological and chemical parameters during vermicomposting of solid
      textile mill sludge mixed with cow dung and agricultural residues.
AB  - In India, thousands of tons of textile mill sludge are produced every year. We
      studied the ability of epigeic earthworm Eisenia foetida to transform textile
      mill sludge mixed with cow dung and/or agricultural residues into value added
      product, i.e., vermicompost. The growth, maturation, mortality, cocoon
      production, hatching success and the number of hatchlings were monitored in a
      range of different feed mixtures for 11 weeks in the laboratory under controlled
      environmental conditions. The maximum growth and reproduction was obtained in
      100% cow dung, but worms grew and reproduced favorably in 80% cow dung + 20%
      solid textile mill sludge and 70% cow dung + 30% solid textile mill sludge also.
      Addition of agricultural residues had adverse effects on growth and reproduction
      of worms. Vermicomposting resulted in significant reduction in C:N ratio and
      increase in TKN, TP, TK and TCa after 77 days of worm activity in all the feeds.
      Vermicomposting can be an alternate technology for the management of textile mill
      sludge if mixed with cow dung in appropriate quantities.

PMID- 15158515
TI  - Allelopathic potential of Citrus junos fruit waste from food processing industry.
AB  - The allelopathic potential of Citrus junos fruit waste after juice extraction was
      investigated. Aqueous methanol extracts of peel, inside and seeds separated from
      the fruit waste inhibited the growth of the roots and shoots of alfalfa (Medicago
      sativa L.), cress (Lepidium sativum L.), crabgrass (Digitaria sanguinalis L.),
      lettuce (Lactuca sativa L.), timothy (Pheleum pratense L.), and ryegrass (Lolium
      multiflorum Lam.). The inhibitory activity of the peel extract was greatest and
      followed by that of the inside and seed extracts in all bioassays. Significant
      reductions in the root and shoot growth were observed as the extract
      concentration was increased. The concentrations of abscisic acid-beta-d
      glucopyranosyl ester (ABA-GE) in peel, inside and seeds separated from the C.
      junos fruit waste were determined, since ABA-GE was found to be one of the main
      growth inhibitors in C. junos fruit. The concentration was greatest in the peel,
      followed by the inside and seeds; there was a good correspondence between these
      concentrations and the inhibitory activities of the extracts. This suggests that
      ABA-GE may also be involved in the growth inhibitory effect of C. junos waste.
      These results suggested that C. junos waste may possess allelopathic potential,
      and the waste may be potentially useful for weed management.

PMID- 15158516
TI  - Influence of the origin of the inoculum and the acclimation strategy on the
      degradation of 4-chlorophenol.
AB  - The influence of the inoculum source and the acclimation strategy on the 4
      chlorophenol (4CP) degradation in a sequencing batch reactor (SBR) was studied.
      Three different sources of inocula were obtained from the aeration tank of
      domestic, municipal and industrial wastewater treatment plants. The acclimation
      was performed using two strategies, the first one fixing the reaction time,
      independent of the removal efficiency (fixed time) and the second one fixing a
      removal efficiency of 90% as 4CP (variable time). The degradative activity was
      followed for each condition. Bacterial identification was carried out at the
      beginning and at the end of the experiments. Variable time strategy produced a
      microbial community with higher specific activity compared with those obtained
      for the fixed time strategy. The microbial activity was dependent of the origin
      of the inoculum. Each inoculum presented different specific activity to 4CP
      degradation. It was observed that the use of the fixed time strategy for the
      acclimation reduced the bacterial community diversity.

PMID- 15158517
TI  - Heavy metals removal by the microalga Scenedesmus incrassatulus in continuous
      cultures.
AB  - The microalga Scenedesmus incrassatulus was grown under continuous regime in the
      presence of chromium(VI), cadmium(II) and copper(II), as single metal species and
      as mixtures of two or three metals, in a laboratory scale system. We used an
      artificial wastewater with low free ion activities (as determined by MINEQL+) due
      to the presence of EDTA (a strong chelating agent) but with total concentrations
      not suitable for acceptable environments. Chromium(VI) and cadmium(II) had
      positive interaction that increased the removal percentages of both these metals;
      we could not, however, detect any interaction with copper(II). S. incrassatulus
      was able to remove all the tested metals to some extent (25-78%), but bivalent
      metals were not removed as efficiently as reported in batch cultures, probably
      due to the high pH values there recorded. Chromium(VI) was more efficiently
      removed in continuous cultures than in batch culture, because the uptake of
      chromate could be favored by actively growing algae.

PMID- 15158519
TI  - What is the contribution of obesity to the metabolic syndrome?
AB  - Many prospective studies show that obesity is accompanied by increased risk for
      cardiovascular disease. Obesity affects metabolism of lipids and glucose,
      regulation of blood pressure, thrombotic and fibrinolytic processes, and
      inflammatory reactions. Multiple aberrations exist in each of these systems;
      obesity acting alone probably is not sufficient to produce full-blown metabolic
      syndrome. There must be other factors, including genetic and aging factors. It is
      difficult to sort out all pathogenic factors that link obesity to cardiovascular
      disease risk. It is worthwhile to investigate individually the components of the
      obesity-induced metabolic syndrome for their atherogenic potential, because out
      of that investigation likely will come new targets for clinical or public health
      intervention to reduce the risk for cardiovascular disease.

PMID- 15158518
TI  - Composting of tannery effluent with cow manure and wheat straw.
AB  - Wastewater from the leather industry in Leon (Guanajuato, Mexico) is discharged
      into the Turbio river without treatment. Tannery wastewater contains utilizable
      nutrients, but also toxic organic compounds which might affect soil processes and
      plant growth, and pathogens, which might pose a threat to the local farming
      community. Tannery effluent was composted with cow manure and wheat straw for 90
      days to reduce pathogens and toxic organic compounds and monitored. The compost
      was characterized by an electrolytic conductivity (EC) of 28.1 ms cm(-1), cation
      exchange capacity of 17.7 meq 100 g(-1), an absorbance at 645 nm of 0.0175, a
      respiration rate of 0.062 mg CO2-C kg(-1) compost-C day(-1), pH 8.5 and C:N ratio
      7:1 with a germination index for cress (Lepidium sativum) of 48% after 90 days.
      Less than 10 faecal coliforms and no Salmonella sp., Shigella sp. or eggs of
      helminthes were detected in the compost while total coliforms decreased by log10
      of 2. Total concentrations of lead (Pb) were 8.9 mgkg(-1) dry compost, chromium
      (Cr) 77 mg kg(-1) dry compost, cadmium (Cd) 0.4 mg kg(-1) dry compost, copper
      (Cu) 10.3 mg kg(-1) dry compost and sodium (Na) 14,377 mg kg(-1) dry compost. The
      compost characteristics indicated that it was mature, but the germination index
      for cress of less than 50% suggested possible remaining phytotoxic compounds.
      However, the large salt concentrations (especially Na), might have inhibited
      cress development and thus reduced the germination index. The large salt
      concentration might thus limit the use of this kind of compost.

PMID- 15158520
TI  - The metabolic syndrome or the insulin resistance syndrome? Different names,
      different concepts, and different goals.
AB  - The goal of this article is to differentiate the insulin resistance syndrome from
      the metabolic syndrome. In the case of the insulin resistance syndrome, the
      abnormalities and clinical syndromes that are increased in prevalence in insulin
      resistant individuals have been summarized, with a brief discussion of the causal
      relationship between insulin resistance, compensatory hyperinsulinemia, and
      associated consequences. Discussion of the metabolic syndrome has focused on the
      five criteria chosen by the adult treatment panel III to diagnose the syndrome,
      evaluating them in terms of their relationship to insulin resistance and their
      role as cardiovascular disease risk factors.

PMID- 15158521
TI  - Lipodystrophies: rare disorders causing metabolic syndrome.
AB  - Recent advances in the understanding of the molecular basis of genetic
      lipodystrophies have promoted understanding of how adipose tissue disorders can
      cause the metabolic syndrome and its complications. These discoveries hold
      promise for elucidating pathways and mechanisms by which common disorders of
      obesity cause metabolic complications. Novel therapeutic approaches for patients
      with lipodystrophies also may have implications for treatment of the metabolic
      syndrome in patients with regional adiposity. This article reviews these recent
      advances in our knowledge of the clinical features, metabolic abnormalities, and
      pathogenetic or other bases of various types of lipodystrophies.

PMID- 15158522
TI  - Prevalence of the metabolic syndrome in US populations.
AB  - The prevalence of the metabolic syndrome using either the National Cholesterol
      Education Program Adult Treatment Panel III or World Health Organization
      definitions is high and likely increasing among US adults. The large number of
      people with the metabolic syndrome has serious implications for public health and
      clinical practice. The associated costs are likely to be substantial. Future
      increases in the incidence of cardiovascular disease and diabetes could occur.
      Because patients with the metabolic syndrome will make up a large proportion of
      the practices of health care professionals, health care professionals must be
      knowledgeable about the metabolic syndrome and be prepared to diagnose it.

PMID- 15158524
TI  - Cardiovascular risk assessment in metabolic syndrome: view from PROCAM.
AB  - The near-epidemic proportions of diabetes mellitus and the metabolic syndrome
      over the past years are widely ascribed to a changing socioeconomic environment
      that contributes to excessive nutritional intake and sedentary lifestyle.
      Paradoxically, this gives room for expectations, because timely lifestyle and
      dietary intervention could decelerate the progression of diabetes, reduce the
      rate of development of cardiovascular complications, and reduce costs associated
      with treatment and rehabilitation. This approach,however, depends on the
      development of tools that allow precise estimation of risk of cardiovascular
      complications before the onset of diabetes mellitus and the risk of developing
      type 2 diabetes itself. This article reviews the progress that has been made
      toward reaching these goals based on the results of the PROspective
      Cardiovascular Munster (PROCAM) study.

PMID- 15158523
TI  - The metabolic syndrome: prevalence in worldwide populations.
AB  - The concept of the metabolic syndrome has now been in existence for several
      decades; however, it has only been since some agreement on definitions of the
      syndrome was reached that it has been possible to compare the prevalence among
      populations worldwide. Just as the prevalence of the individual components of the
      syndrome varies among populations, so does the prevalence of the metabolic
      syndrome itself. Differences in genetic background, diet,levels of physical
      activity, population age and sex structure, levels of over- and undernutrition,
      and body habitus all influence the prevalence of both the metabolic syndrome and
      its components. Regardless of the underlying genetic and environmental influences
      that mediate the prevalence of the metabolic syndrome, a higher prevalence will
      undoubtedly lead to undesirable outcomes such as cardiovascular disease.

PMID- 15158525
TI  - Metabolic abnormalities: high-density lipoproteins.
AB  - The dyslipidemia typically found in subjects with the metabolic syndrome includes
      an elevated concentration of plasma triglyceride,a low-density lipoprotein
      fraction in which the particles are smaller and denser than normal, and a low
      concentration of highdensity lipoprotein (HDL) cholesterol. This article is
      concerned with the low HDL component. It provides an overview of HDL structure
      and metabolism and describes the functions of HDLs that may be cardioprotective.
      The article then outlines what is known about the concentration and subpopulation
      distribution of HDLs in the metabolic syndrome. Possible mechanisms responsible
      for the low HDL are discussed. The consequences of a low HDL concentration in
      this syndrome are addressed before the article concludes with a discussion of
      whether low HDL in the metabolic syndrome should be a therapeutic target.

PMID- 15158526
TI  - Metabolic abnormalities: triglyceride and low-density lipoprotein.
AB  - Increased plasma triglyceride and reduced high-density lipoprotein cholesterol
      are key features of the metabolic syndrome. Although elevated low-density
      lipoprotein cholesterol is not an integral characteristic of this syndrome, there
      is commonly an increase in the proportion of small, dense low-density lipoprotein
      particles. Together, these abnormalities constitute the atherogenic dyslipidemia
      of the metabolic syndrome. This article reviews the pathophysiology of altered
      triglyceride and low-density lipoprotein metabolism in the metabolic syndrome,
      outlines the relationship of these lipoprotein abnormalities to increased risk of
      coronary heart disease,and highlights the application of this information to
      clinical practice. The role of reduced high-density lipoprotein in the metabolic
      syndrome is discussed elsewhere in this issue.

PMID- 15158527
TI  - Hypertension, insulin resistance, and the metabolic syndrome.
AB  - Impaired glucose homeostasis, hypertriglyceridemia, low high-density lipoprotein
      cholesterol, high blood pressure, and central obesity tend to cluster in patients
      to generate a syndrome, the metabolic syndrome. In the adult population, the
      metabolic syndrome prevalence ranges between 15% and 25%. Poor fibrinolysis and
      low-grade inflammation also are associated with the metabolic syndrome,and they
      contribute to make it a condition that predisposes to cardiovascular disease.
      Insulin resistance and attendant hyperinsulinemia are the characteristic features
      of the metabolic syndrome and probably are responsible for impairment in glucose
      homeostasis,dyslipidemia, and higher blood pressure through cause-and-effect
      relationships. While awaiting the results of clinical trials with cardiovascular
      endpoints, we should treat the metabolic syndrome with aggressive lifestyle
      intervention and consider drugs that improve the whole cardiovascular risk
      profile.

PMID- 15158528
TI  - Metabolic syndrome: an appraisal of the pro-inflammatory and procoagulant status.
AB  - Inflammation and hypercoagulability predispose to atherothrombosis and seem to be
      important features of the metabolic syndrome. The most convincing evidence is the
      association with increased levels of C-reactive protein. The hemostatic
      abnormality that has been most consistently associated with insulin resistance is
      an elevated plasminogen activator inhibitor-1 level. In contrast, markers of
      hypercoagulability have been associated inconsistently with hyperinsulinemia and
      glucose intolerance. Fibrinogen clusters with inflammatory factors, which
      suggests involvement of adipose tissue-generated inflammatory cytokines. Elevated
      von Willebrand's factor and factor VIII levels aggregate with indicators of
      endothelial injury,whereas vitamin K-dependent coagulation proteins correlate
      with triglyceride levels.

PMID- 15158529
TI  - Metabolic syndrome: part I.

PMID- 15158530
TI  - Pulsatile secretion pattern of vasopressin under basal conditions, after water
      deprivation, and during osmotic stimulation in dogs.
AB  - Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration
      in response to hypertonicity is regarded as the gold standard for the assessment
      of VP release in polyuric conditions. Yet the interpretation of the VP curve as a
      function of Posm may be hampered by the occurrence of VP pulses. To determine
      whether VP is secreted in a pulsatile fashion in the dog and whether stimulation
      of VP release changes the secretion pattern of VP, we measured VP at 2-min
      intervals for 2 h under basal conditions, after 12 h of water deprivation, and
      during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs.
      Vasopressin was secreted in a pulsatile fashion with a wide variation in number
      of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water
      deprivation, total and basal VP secretion, the number of significant VP pulses,
      as well as the pulse characteristics did not differ from the basal situation.
      During osmotic stimulation, there was a large increase in both basal and
      pulsatile VP secretion, and the number of VP pulses and VP pulse height and
      amplitude were significantly increased. The VP pulse amplitude correlated
      significantly with the basal plasma VP concentration during osmotic stimulation.
      It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The
      basal and pulsatile VP secretion increases during osmoreceptor-mediated
      stimulation. The VP pulses may occur to the magnitude that they may be
      interpreted as erratic bursts, when occurring in the hypertonic saline infusion
      test.

PMID- 15158531
TI  - Urinary glucocorticoid excretion in the diagnosis of hyperadrenocorticism in
      ferrets.
AB  - Hyperadrenocorticism in ferrets is usually associated with unaltered plasma
      concentrations of cortisol and adrenocorticotropic hormone (ACTH), although the
      urinary corticoid/creatinine ratio (UCCR) is commonly elevated. In this study the
      urinary glucocorticoid excretion was investigated in healthy ferrets and in
      ferrets with hyperadrenocorticism under different circumstances. In healthy
      ferrets and in one ferret with hyperadrenocorticism, approximately 10% of plasma
      cortisol and its metabolites was excreted in the urine. High-performance liquid
      chromatography (HPLC) revealed one third of the urinary corticoids to be
      unconjugated cortisol; the other peaks mainly represented cortisol conjugates and
      metabolites. In 21 healthy sexually intact ferrets, the UCCR started to increase
      by the end of March and declined to initial values halfway the breeding season
      (June). In healthy neutered ferrets there was no significant seasonal influence
      on the UCCR. In two neutered ferrets with hyperadrenocorticism the UCCR was
      increased, primarily during the breeding season. In 27 of 31 privately owned
      ferrets with hyperadrenocorticism, the UCCR was higher than the upper limit of
      the reference range (2.1 x 10(-6)). In 12 of 14 healthy neutered ferrets
      dexamethasone administration decreased the UCCR by more than 50%, whereas in only
      1 of the 28 hyperadrenocorticoid ferrets did the UCCR decrease by more than 50%.
      We conclude that the UCCR in ferrets primarily reflects cortisol excretion. In
      healthy sexually intact ferrets and in ferrets with hyperadrenocorticism the UCCR
      increases during the breeding season. The increased UCCR in hyperadrenocorticoid
      ferrets is resistant to suppression by dexamethasone, indicating ACTH-independent
      cortisol production.

PMID- 15158532
TI  - Influence of prenatal testosterone treatment on foetal and prepubertal LHbeta
      subunit mRNA and plasma LH concentrations in the female pig.
AB  - The aim of this study was to investigate the potential role of foetal androgens
      in determining the sexual dimorphism in LH gene expression. Starting on day 30
      p.c. pregnant sows were treated i.m. with testosterone propionate (TP) three
      times at 2-day intervals (TP30 treatment) or received additional TP treatment
      starting on day 40 p.c. (TP30/40). Sows were allowed to farrow and after frequent
      blood samples for LH determination were collected prepubertally (6 months) from
      the female offspring anterior pituitary LHbeta subunit mRNA levels were
      determined. In Experiment 2 pregnant sows were treated as TP30 before or received
      similar treatment starting on day 40 p.c. (TP40), but anterior pituitary LHbeta
      mRNA and plasma LH concentrations were determined at day 80 p.c. TP30 or TP30/40
      treatment did not affect mean plasma LH concentrations nor LHbeta mRNA levels at
      6 months of age but caused marked masculinization of external genitalia. At day
      80 p.c. LHbeta mRNA and plasma LH levels were higher in female than in male
      foetuses. TP40 treatment suppressed LHbeta mRNA and plasma LH levels while TP30
      treatment had no effect on LHbeta mRNA levels but caused masculinization of
      external genitalia in contrast to TP40. Our findings support the notion that the
      peak in plasma testosterone observed by others in the male pig foetus 5 weeks
      p.c. not only determines sexual differentiation of the LH surge mechanism but
      also LH gene expression in the foetus. The critical period for this process seems
      to succeed phenotypic differentiation (which appears to be largely completed
      before day 40 p.c.). The tonic mode of prepubertal LH gene expression and LH
      secretion in female pigs is not affected greatly by testosterone treatment at the
      stages of development that were investigated.

PMID- 15158533
TI  - Identification of interferon-tau isoforms expressed by the peri-implantation goat
      (Capra hircus) conceptus.
AB  - Interferon-tau (IFN-tau) is the maternal recognition of pregnancy factor in
      pecoran ruminants. The aims of this study were to identify the various IFN-tau
      transcripts in the peri-implantation caprine (ca) conceptus and to compare these
      nucleotide sequences phylogenetically with established mRNA sequences from the
      goat. Conceptuses (n = 5) were collected from Boer crossbred and Angora female
      goats by laparotomy at days 17 and 18 of pregnancy. Total cellular RNA was
      extracted and RT-PCR was performed by standard procedures using a DNA polymerase
      with proofreading activity and gene-specific primers complimentary to non-coding
      regions of the published caIFN-tau sequence. Nine distinct nucleotide sequences
      were isolated that encode five distinct caIFN-tau proteins. These caIFN-tau have
      greater sequence homology with ovine IFN-tau (94-96% nucleotide identity; 90-93%
      amino acid identity) than with bovine IFN-tau (<92% nucleotide identity; <85%
      amino acid identity). The novel caIFN-tau isoforms contained pronounced
      nucleotide and amino acid sequence identity with one another (97-99% nucleotide
      identity; 94-99% amino acid identity) but only moderate sequence identity with
      the previously identified caIFN-tau (94-96% nucleotide identity; 87-90% amino
      acid identity). In conclusion, multiple caIFN-tau mRNA species are expressed
      during peri-implantation conceptus development and distinct clusters of caIFN-tau
      genes appear to have evolved in this species.

PMID- 15158534
TI  - Peripheral leptin effect on food intake in young chickens is influenced by age
      and strain.
AB  - The acute effect of leptin on the regulation of food intake was investigated in
      layer and broiler chickens. In an initial study, we observed that a single
      intraperitoneal injection of recombinant chicken leptin (1 mg/kg BW) dramatically
      reduced (38%) food intake in 56-day-old layer chickens, more moderately reduced
      (15%) food intake in 9-day-old layer chicks, and had no significant effect in 9
      day-old broiler chicks. In a subsequent study, body weight and plasma
      concentrations of leptin were measured weekly in layer and broiler chicks from
      day 1 to 35 of age and brain leptin receptor and neuropeptide Y (NPY) mRNA
      expression were analyzed at 1, 9, and 35 days of age. At day 1 of age, peripheral
      concentrations of leptin were significantly greater in layer than broiler chicks.
      Subsequently, despite increases in body weight and differences in growth rates
      between layer and broiler chicks from day 8 to day 35 of age, peripheral
      concentrations of leptin were constant and similar in both genotypes. Leptin
      receptor and NPY mRNA were expressed in brain from day 1 in chicks of both
      genotypes and increased significantly to day 35 of age. These observations
      provide evidence that the inhibitory effect of leptin on the regulation of food
      intake in growing chicks is an age dependent process. Furthermore, acquisition of
      the anorectic effect of leptin is likely to be associated with greater expression
      of the leptin receptor and NPY mRNAs than to changes in blood levels of leptin.
      Finally, this study provides evidence that chickens selected for high growth
      rates may be less sensitive or responsive to peripheral concentrations of leptin
      than chickens with low growth rates (layers), suggesting that the faster growth
      of broiler chicks may be related to a lessened responsiveness to anorexigenic
      factors.

PMID- 15158536
TI  - Androgen receptor mRNA expression in the bovine ovary.
AB  - Previous studies have shown that androgen receptor (AR) is expressed in granulosa
      cells of healthy, growing ovarian follicles in rats and primates. However, AR
      expression in the bovine ovary has not been examined. Therefore, a 346-base pair
      segment of the bovine AR was cloned and sequenced. Using a ribonuclease
      protection assay, AR expression was detected in total RNA from bovine ovarian
      cortex. Expression (absence or presence) of AR mRNA was detected by in situ
      hybridization in bovine ovarian cortex. Follicles (n = 32) were classified as
      follows: type 1 (1 layer of flattened granulosa cells), type 2 (1-1.5 layers of
      cuboidal granulosa cells), type 3 (2-3 layers of granulosa cells), type 4 (4-6
      layers of cuboidal granulosa cells and formation of thecal layer), and type 5 (>6
      layers of cuboidal granulosa cells, defined theca layer, and antrum formation).
      Frequency of AR mRNA expression increased (P < 0.001) as follicles entered the
      growing pool. Expression of AR mRNA was absent in type 1 follicles (n = 8), but
      present in the granulosa cells of 41% of type 2 follicles (n = 12). In types 3-5
      follicles, AR mRNA expression was present in granulosa cells of 100% of follicles
      examined (n = 4, 4, and 4, respectively) and was greater than type 1 follicles (P
      = 0.002). These data provide evidence of AR mRNA expression in bovine follicles
      and suggest that AR mRNA increases during early follicle development.

PMID- 15158535
TI  - Prostaglandin F2alpha (PGF2alpha) independent and dependent regulation of the
      bovine luteal endothelin system.
AB  - We have examined the genes of the endothelin system that are targets for
      regulation by prostaglandin F2alpha (PGF2alpha). The effects of a luteolytic dose
      of PGF2alpha ) on the mRNA encoding endothelin converting enzyme-1 (ECE-1), pre
      pro endothelin-1 (pp ET-1) and the ET receptors ETA, ETB, in bovine corpus luteum
      (CL) during the early (days 1 and 4), mid (day 10) or late (day 17) luteal phases
      were examined. The effect of the PGF(2alpha) treatment on ECE-1 protein, Big ET-1
      and the biologically active mature ET-1 peptide were also examined. Most
      importantly, the direct ECE-1 activity was determined. Before day 10 of the
      cycle, in a PGF2alpha-independent manner, the amounts of mRNA encoding ET-1, ECE
      1, ETA, and ETB were increased steadily from day 1. After day 10 of the cycle,
      expression of mRNA encoding pp ET-1 and ETA acquired responsiveness to exogenous
      PGF2alpha and both genes were up-regulated by the PGF2alpha treatment. This
      effect of PGF2alpha was also detected for the proteins corresponding to the
      mature ET-1. The enzymatic activity of ECE-1 remained unchanged throughout the
      lifespan of the CL in spite of the detected changes in mRNA and protein. The
      results suggest that the luteal endothelin system is regulated in a PGF2alpha
      independent and -dependent manner. Importantly, an alteration in luteal ET-1
      availability is most likely achieved by modulating the expression of mRNA
      encoding pp ET-1 and not by the amount or activity of ECE-1. This interpretation
      is supported by the observation that the activity of ECE-1 remained unchanged
      throughout the ovarian cycle. The combined effects of greater ET-1 availability
      and gene expression encoding the ETA receptor in the late luteal phase could
      render the CL, at this developmental stage, more sensitive or responsive to ET-1.
      If the luteal tissue is responsive to the available ET-1 during the early phase
      of the ovarian cycle, an additional role for ET-1 should be considered beyond
      mediating the luteolytic actions of PGF2alpha. Agents blocking the actions of ET
      1 might be the best approach to interfere with the luteal ET system and test its
      physiological role(s) in vivo.

PMID- 15158537
TI  - Commentary: Botulinum toxin in clinical medicine: part II.

PMID- 15158538
TI  - Facial anatomy.
AB  - Botulinum toxin acts at the neuromuscular endplate, which requires precise
      delivery of the drug to achieve a desired clinical result. A thorough
      understanding of the complex anatomic structures of the face and their effect on
      facial form and function, coupled with an appreciation of facial esthetics and
      the balanced muscle actions that produce resting and active facial form, will
      result in accurate and reproducible clinical effects. Utilizing some general
      anatomic principles in combination with specific individual facial features and
      variations will enable the physician to consistently find the optimum injection
      sites and combination of other therapies for desired outcomes.

PMID- 15158539
TI  - Facial esthetics and patient selection.
AB  - Preventing patient dissatisfaction is a primary goal when performing botulinum
      toxin-A injections. By taking the correct approach with careful patient
      selection, ensuring safety and minimizing the risk of complications and side
      effects, the practitioner can largely eliminate patient dissatisfaction with this
      therapy. Basic understanding of facial esthetics and concepts of beauty are
      helpful to optimize patient satisfaction.

PMID- 15158540
TI  - Cosmetic uses of botulinum toxins for lower aspects of the face and neck.
AB  - The ability of botulinum toxin A (BTX-A) to improve the appearance of facial
      lines was first reported among patients who had been receiving injections for
      facial dystonias or surgical procedures. Since that time, there has been very
      extensive use of this treatment for relaxation of a wide variety of facial
      muscles and also for platysmal lines of the neck. Considerable experience over
      the last decade or longer confirms the safety and efficacy of BTX-A in the
      treatment of upper facial lines. BTX-A has been used also lower facial
      indications, but published papers are mainly uncontrolled observations on
      patients. Unlike the placebo-controlled studies on the upper face, there is a
      lack of controlled studies for lower face and neck BTX-A treatment. This article
      will summarize the use of BTX-A for the lower face and its role as combination
      treatment. Examples of combinations that may be used with BTX-A resurfacing,
      nonablative skin rejuvenation and skin fillers. Although little used at present,
      Botulinum Toxin B will be briefly discussed.

PMID- 15158541
TI  - Botulinum toxin type B (Myobloc): pharmacology and biochemistry.
AB  - Purified toxin complexes have found a niche in the treatment of clinical
      disorders involving muscle hyperactivity. This report describes the fundamental
      biochemical properties of the commercially available form of Botulinum Toxin Type
      B and compares these attributes to the Type A form of the Toxin. Both neurotoxins
      act to inhibit the release of acetylcholine at the neuromuscular junction,
      causing muscle paralysis. The different serotypes are structurally and
      functionally similar; however, specific differences in neuronal acceptor binding
      sites, intracellular enzymatic sites, and species sensitivities suggest that each
      serotype is its own unique pharmacologic entity. Data are provided on the
      biochemical properties and long-term stability of the Type B product, which is
      uniquely formulated as a liquid product.

PMID- 15158542
TI  - The cosmetic use of botulinum toxin type B in the upper face.
AB  - Facial wrinkles involving the forehead, glabellar, and/or periorbital regions are
      a common esthetic problem and are directly related to overactivity of the
      underlying facial musculature. For instance, the development of glabellar
      wrinkles is related, at least in part, to the dynamics of the underlying
      procerus, corrugator supercilii, and orbicularis oculi muscles. Facial lines are
      considered problematic because they produce the appearance of aging. In some
      cases, they can also be misinterpreted as manifestations of negative emotions
      (eg, anger, anxiety, sadness), fatigue, or stress. In recent years, botulinum
      toxin injections have become one of the most popular therapies for the treatment
      of hyperfunctional facial lines. After injection, the toxin acts to paralyze or
      weaken facial mimetic muscles. This reduces or eliminates the appearance of
      wrinkles and is extremely safe.

PMID- 15158543
TI  - Botulinum toxin types A and B: comparison of efficacy, duration, and dose-ranging
      studies for the treatment of facial rhytides and hyperhidrosis.
AB  - One of the most common etiologic forces for the persistence of facial rhytides is
      the repetitive contraction of the intrinsic muscles that are necessary for facial
      expression. These include the forehead lines, crow's feet, glabellar rhytides,
      and wrinkles in the lower face. Although filling agents such as collagen and
      laser procedures can help reduce the appearance of these lines, they do not
      address the underlying forces that cause these wrinkles to persist. Botulinum
      toxin type-A and type-B are neurotoxins that address these issues and result in
      the relaxation of the intrinsic facial muscles and subsequent resolution of these
      dynamic facial rhytides. This article will compare the efficacy, duration, dose
      ranging studies, and safety in the treatment of facial rhytides with both types
      of toxins. In addition, the treatment of hyperhidrosis with type-A and type-B
      botulinum toxin will also be discussed.

PMID- 15158544
TI  - Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive
      syndromes associated with hyperhidrosis.
AB  - For a long period the therapeutic modalities to treat focal hyperhidrosis (HH)
      were very limited. Due to this the problem of focal HH was delt with
      stepmotherly. Nowadays we can consider BTX as the therapy of choice for axillary
      HH after topical treatment with aluminium salts have failed. The amount of
      successful reports on botulinum toxin (BTX) in the treatment of focal HH brought
      a change and the interest for this specific disorder grew. This article gives
      details on anatomy and physiology of sweating and mechanism of BTX. Further
      distinctive syndromes associated with HH, which all can be treated with BTX like
      localized unilateral hyperhidrosis (LUH), Ross' Syndrome and Frey' Syndrome are
      presented. A diagnosis of primary HH is usually based on the patients's history,
      typical younger age and visible signs of excessive sweating. Before treatment it
      is important to objectify focal HH with performing sweat tests such like Minor
      starch test and/or gravimetry. The total number of sweat glands is somewhere
      between 2 and 4 million and only about 5% are active at the same time, indicating
      the enormous potential for sweat production. The eccrine sweat gland is a long
      branched tubular structure with highly coiled secretory portion and a straight
      ductular portion. Sweat is produced by clear and dark cells and is a clear
      hypotonic, odorless fluid. In response to nerve impulses, Acetylcholine (ACh) is
      released from the presynaptic nerve endings and then binds to postsynaptic
      cholinergic receptors presumably present in the basolateral membrane of the clear
      cells. This activates a complex in- and efflux of electrolytes creating the
      hypotonic sweat. Injection of BTX leads to temporary chemodenervation with the
      loss or reduction of activity of the target organ. BTX is consisted of a heavy
      and a light chain. The structural architecture of BTX comprises three domains-L,
      H(N) and H(C)-each with a specific function in the mechanism of cell
      intoxication. The heavy chain is responsible for binding to the nerve cell,
      whereas the light chain catalyzes the proteolysis of one of the three SNARE
      proteins (Snap-25, Vamp or Syntaxin) depending to the serotype of BTX (7
      serotypes A-G). Once cleaved by BTX, the SNARE proteins cannot become part of the
      complex capable of mediating the vesicle membrane fusion and therefore prevents
      the release of ACh and hence transmission of the nerve impulse.

PMID- 15158545
TI  - Hyperhidrosis and botulinum toxin A: patient selection and techniques.
AB  - Focal idiopathic excessive eccrine sweating presents most commonly as an
      affliction of three anatomically distinct area: the axillae, the palms and soles,
      and the upper face. The true incidence is not known, but about half of the
      patients referred to us with this condition have at least one first-degree
      relative similarly affected. Only a fraction of patients afflicted are thought to
      seek medical care because of the social stigma, lack of understanding on the part
      of medical providers as to the cause and nature of the problem, and, until now,
      lack of effective nonsurgical therapy. A large social sample is required to
      accurately measure both the incidence and the exact nature of the genetic
      influence.

PMID- 15158546
TI  - Inguinal, or Hexsel's hyperhidrosis.
AB  - Inguinal Hyperhidrosis (IH) is a focal and primary form of hyperhidrosis in which
      the individual has intense sweating in the inguinal region. It usually appears in
      adolescence, not later than the age of 25, in the most cases, and continues into
      adulthood. With a sample of 26 patients we described Inguinal Hyperhidrosis (IH).
      Fifty percent of the patients have a positive family history of this condition or
      other forms of focal or generalized hyperhidrosis, which suggests a familial
      pattern. Biopsies performed on the inguinal area in a patient with IH and control
      patient showed normal histology. Excessive perspiration in the inguinal area
      significantly affects the quality of life of the patients. It is an embarrassing
      condition that produces large wet stains on the clothes, therefore making daily
      activities difficult and compromising the emotional, professional and social life
      of the affected patients. The therapies commonly used for other forms of focal
      hyperhidrosis are not yet referred in the literature specifically for IH.
      Intradermal injections from botulinum toxin provide positive results for the
      patients and controls the sweating for 6 months or more. It is a simple, safe and
      effective treatment for this condition and the results significantly improve the
      quality of life of the affected individuals.

PMID- 15158547
TI  - Botulinum toxin-B and the management of hyperhidrosis.
AB  - A new serotype of botulinum toxin has recently arrived in the US. Botulinum toxin
      type B (BTX-B), known as Myobloc in the United States and as Neurobloc in Europe,
      is one of seven different antigenic members of the botulinum toxin family, five
      of which the human nervous system is susceptible to. Like botulinum toxin type A
      (BTX-A), BTX-B has been used for a myriad of both dermatologic and
      nondermatologic problems since its recent approval by the FDA for the treatment
      of cervical dystonia in December 2000. It is currently not approved however, for
      a cosmetic use but has been used for this purpose in an "off-label" fashion. It
      has followed in the therapeutic footsteps of BTX-A in the prevention and
      treatment of facial wrinkles such as crow's feet and glabellar frown lines. In
      addition, one of its current and popular uses is in the management of
      hyperhidrosis, a disease in search of a long needed treatment. This past year
      researchers have been investigating the efficacy as well as defining the dosing
      and application regiments of BTX-B in the treatment of hyperhidrosis. In
      addition, recent studies have been examining its side effect profile, which may
      be very different than that seen with BTX-A. There are only a handful of studies
      in the literature examining the cosmetic applications of BTX-B. This chapter will
      review what is currently known about BTX-B and its current use in regards to the
      treatment of hyperhidrosis.

PMID- 15158548
TI  - Contraindications and complications with the use of botulinum toxin.
AB  - Cosmetic use of BTX has skyrocketed in recent years, especially since the
      approval of BTX-A for treatment of glabellar lines. Complications and adverse
      reactions can easily arise, particularly for the novice injector. This paper
      provides insights from an experienced physician on how to avoid these
      complications, and how to treat them when and if they occur. The main cosmetic
      uses for BTX are analyzed for possible complications and adverse events.
      Injection techniques are discussed. Comparisons between BTX-A and BTX-B are given
      to point out the need for different injection techniques based on the product
      being used. Treatment recommendations for the Glabella, Brow, Crow's Feet, Upper
      Lip Wrinkling/Lines, Depressor Anguli Oris, Nasolabial Folds, Mentalis, Neck and
      Hyperhidrosis are discussed, as well as systemic complications. It is important
      for the injecting physician to be familiar with these potential complications,
      even though the use of BTX has been safe and generally well tolerated, because it
      will lead to even greater success with the use of BTX.

PMID- 15158549
TI  - Botulinum neurotoxin for the treatment of migraine and other primary headache
      disorders.
AB  - Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of
      disorders of involuntary muscle contraction, including cervical dystonia,
      blepharospasm and hemifacial spasm. It inhibits neurouscular signaling by
      blocking the release of acetylcholine at the neuromuscular junction. The
      biological effects of the toxin are transient with normal neuronal signaling
      returning within approximately 3-6 months post injection. Recently, clinical
      findings suggest that BoNT/A may inhibit pain associated with migraine and other
      headache types. The mechanism by which this toxin inhibits pain is under
      investigation, recent findings suggest that it inhibits the release of
      neurotransmitters from nociceptive nerve terminals and in this way may exert an
      analgesic effect. A number of retrospective open-label chart reviews and three
      placebo-controlled double-blind trials have demonstrated that localized
      injections of BTX-A significantly reduce migraine frequency, severity, and
      migraine-associated disability. The majority of patients in these studies
      experienced no BoNT/A mediated side effects; however, a small percentage of
      patients did report transient minor side effects including blepharoptosis,
      dipolpia, and injection-site weakness. Currently there are several large-scale
      randomized, placebo-controlled clinical trials in progress evaluating the
      efficacy, optimal dosing and side effect profile of this toxin as a novel
      treatment for migraine and other headache types. These studies may provide
      further evidence that BoNT/A is an effective option for the preventive treatment
      of migraine.

PMID- 15158550
TI  - Noncosmetic uses of botulinum toxin.
AB  - Since the introduction of botulinum toxin (BTX) as a therapeutic tool in the
      1970s, the number of uses for this substance has increased exponentially. BTX's
      mechanism of action involves degrading the SNARE proteins blockading the release
      of acetylcholine into the neuromuscular junction. In many body systems, decrease
      of contractility, strength, and tension of certain muscle groups result in
      improved clinical outcomes. Applications now include cosmetic, gastroenterologic,
      otolaryngologic, genitourinary, neurologic, and dermatologic uses. In fact, BTX
      can be considered as a potential treatment in any situation involving
      inappropriate or exaggerated muscle contraction. Currently, the FDA has approved
      BTX-A (Botox) for treating glabellar lines, blepharospasm, strabismus, hemifacial
      spasm, cervical dystonia, and spasticity. With the addition of cosmetic
      applications to the FDA's approval list, the use of BTX has increased
      dramatically.

PMID- 15158551
TI  - Botox: beyond wrinkles.
AB  - First used and approved over a decade ago for the treatment of strabismus (or
      misaligned eyes), botulinum toxin (BTX) has demonstrated efficacy in
      blepharospasm, hemifacial spasm, spastic lower eyelid entropion, and a number of
      other disorders seen in the traditional medical environment that are
      characterized by abnormal muscle contraction. Moreover, other conditions-notably
      some pain and gastrointestinal disorders-have responded to BTX injections.

PMID- 15158552
TI  - A cross-sectional epidemiological survey of bovine trypanosomosis and its vectors
      in the Savelugu and West Mamprusi districts of northern Ghana.
AB  - The epidemiology of bovine trypanosomosis was investigated in two districts
      (Savelugu and West Mamprusi) of Northern Ghana with different land use and
      environmental characteristics. The land use intensity and environmental change
      was suspected to be higher in the Savelugu District. A cross-sectional
      entomological survey conducted along the White Volta river and its tributaries
      confirmed the presence of only Glossina palpalis gambiensis and G. tachinoides.
      The challenge index as measured by the product of tsetse density and tsetse
      infection rate was much higher in the West Mamprusi (19.6) than in the Savelugu
      district (4.7). A total of 1013 cattle (508 in Savelugu and 505 in West Mamprusi)
      were bled from a random selection of 16 villages in the Savelugu District and 13
      villages in the West Mamprusi District. Blood samples were examined for
      trypanosomes by the buffy coat technique (BCT). Blood samples that were positive
      in the BCT or negative in the BCT but with packed cell volume (PCV) values below
      21 were further tested with a polymerase chain reaction for trypanosomal DNA.
      Plasma samples of all cattle were serologically tested with an indirect ELISA for
      trypanosomal antibodies. The parasitological and serological prevalence of bovine
      trypanosomoses was significantly higher in West Mamprusi (16 and 53%,
      respectively) than in Savelugu District (8 and 24%, respectively). An evaluation
      of animal health at the village herd level, using PCV as an index of anaemia,
      provided various epidemiological scenarios prevalent in the entire study area.

PMID- 15158553
TI  - Use of remote sensing and geographical information systems to identify
      environmental features that influence the distribution of paramphistomosis in
      sheep from the southern Italian Apennines.
AB  - A geographic information system (GIS) was constructed using remote sensing (RS)
      and landscape feature data together with Calicophoron daubneyi positive survey
      records from 197 georeferenced ovine farms with animals pasturing in a 3971 km(2)
      area of the southern Italian Apennines. The objective was to study the spatial
      distribution of this rumen fluke, identify environmental features that influence
      its distribution, and develop a preliminary risk assessment model. The GIS for
      the study area was constructed utilizing the following environmental variables:
      normalized difference vegetation index (NDVI), land cover, elevation, slope,
      aspect, and total length of rivers. These variables were then calculated for
      "buffer zones" consisting of the areas included in a circle of 3 km diameter
      centered on 197 farms. The environmental data obtained from GIS and RS and from
      data taken by the veterinarians on the field (stocking rate and presence of
      streams, springs and brooks on pasture) were analyzed by univariate (Spearman and
      ANOVA) and multivariate (discriminant) statistical analyses using the farm
      coprological status (positive/negative) as the dependent variable. Sheep on 32 of
      the 197 (16.2%) farms, were positive for C. daubneyi, with an average intensity
      of 52 epg. A multivariate stepwise discriminant analysis model was developed that
      included moors and heathland, sclerophyllous and coniferous forest vegetation,
      autumn-winter NDVI and presence of streams, springs and brooks on pasture. The
      variables entered in the model were also correlated with C. daubneyi positive
      farms in the univariate tests and are consistent with the environmental
      requirements of C. daubneyi and its snail intermediate host.

PMID- 15158554
TI  - The role of the subterranean rodent Ctenomys talarum (Rodentia: Octodontidae) in
      the life cycle of Taenia taeniaeformis (Cestoda: Taeniidae) in urban
      environments.
AB  - This work is the first report of subterranean rodent Ctenomys talarum (Rodentia:
      Octodontidae) as intermediate host of Taenia taeniaeformis in urban areas of Mar
      de Cobo (Buenos Aires Province, Argentina) and to experimentally reproduce in
      domestic dogs the adult stage of this parasite. Prevalence, mean abundance and
      mean intensity of infection with T. taeniaeformis larvae in the liver and
      peritoneal cavity of C. talarum were 64%, 15.3 and 9.8, respectively. Ten adults
      of T. taeniaeformis were obtained from experimentally infected dogs. Information
      about the role of subterranean rodents in the life cycle of this parasite is also
      given. The above mentioned data indicate that T. taeniaeformis is a frequent
      parasite of this species of rodents, at least within the study area. Also
      explanations for the high prevalence of larval forms of this parasite in C.
      talarum populations are given.

PMID- 15158555
TI  - Onchocerca ochengi acquisition in zebu Gudali cattle exposed to natural
      transmission: parasite population dynamics and IgG antibody subclass responses to
      Ov10/Ov11 recombinant antigens.
AB  - Ngaoundere Gudali zebu cattle naturally exposed to Simulium damnosum s.l. and
      Culicoides spp. bites were examined during 4 years for O. ochengi adult worm
      acquisition, Onchocerca ochengi and Onchocerca gutturosa skin microfilaria
      dynamics, and IgG1 and IgG2 antibody subclass responses. Eleven animals acquired
      a total of 465 O. ochengi nodules (average of 17 per female and 72 per male). The
      O. ochengi nodule load was highly variable in individual animals and exacerbated
      in mature male cattle. Three patterns of acquisition of O. ochengi (resistant to
      new infestation, early susceptibility and late susceptibility), not associated
      with Simulium biting intensity (P > 0.05), were distinguished. The minimum
      prepatent periods for O. ochengi nodules, O. ochengi microfilariae and O.
      gutturosa microfilariae were 10, 20 and 21 months, respectively. The O. ochengi
      microfilaria density significantly (P < 0.001) increased with age, was higher in
      young mature bulls than female animals (P < 0.001) and finally reached highest
      levels (P < 0.005) during the dry season. Antibody responses to Ov10/Ov11
      recombinant O. volvulus antigens were predominantly of the IgG1 subclass. High
      levels of this subclass (not IgG2) observed in new born calves declined to almost
      zero levels at the age of 5-8 months but IgG1 levels significantly increased (P <
      0.05) with age subsequently during patency. Put together the acquisition and
      accumulation of O. ochengi parasites in zebu cattle, apart from being season, sex
      (gender) and host age associated, may also suggest a density-dependent regulation
      of parasite establishment in a proportion of the exposed population.

PMID- 15158556
TI  - Variability in the resistance of the Nigerian West African Dwarf goat to
      abbreviated escalating trickle and challenge infections with Haemonchus
      contortus.
AB  - The West African Dwarf (WAD) goat is known to be relatively resistant to
      infection with Haemonchus contortus. An experiment was carried out to assess
      variability in resistance under escalating trickle and single pulse challenge
      infection protocols. Thirty two 7-8 month old goats were subjected to trickle
      infection beginning with a thrice weekly dose of 100 L3 and increasing to 500 L3
      by week 5, the last dose being administered on D30. Infection was abbreviated
      with fenbendazole on D32 and the animals challenged with 4000 L3 (=404-741L3/kg
      body weight) on D46 and necropsied on D81. The goats exhibited marked individual
      variability in faecal egg counts (FEC) and worm burdens (Wb). For convenience, we
      arranged the goats into FEC classes 1, 2 and 3, corresponding to peak counts of
      <1000, 1000-2500 and >2500 epg and Wb classes 1, 2 and 3, with counts of <50, 50
      100 and >100 worms, respectively, broadly reflecting relatively resistant,
      intermediate and poorly resistant response phenotypes. Wb classes broadly
      reflected the FEC phenotypes and although there were no significant differences
      between the Wb of the FEC classes at necropsy, significant differences in FEC
      were detected when analysis was carried out only on Wb classes. There was also a
      significant positive correlation between FEC class on each of the days of
      challenge (D67 to D80) and worm burden at necropsy. In general, the goats showed
      strong resistance/tolerance to challenge, with more than 80% having Wb not
      exceeding 5% of the challenge dose, and only in class three goats were weight
      loss and anaemia detected in some animals. PCV and weight changes also closely
      reflected the FEC and Wb classes, with a significant negative correlation between
      each and Wb. Infection level did not significantly affect the sizes of either
      male or female worms and no significant difference was detected between the
      levels of circulating eosinophils in any FEC or Wb class. Overall, the data are
      consistent with the existence of a range of response phenotypes, which reflect
      variations in resistance of WAD goats to H. contortus infection, the genetic
      basis of which will be explored in future experiments.

PMID- 15158557
TI  - Humoral immune response of water buffalo monitored with three different antigens
      of Toxocara vitulorum.
AB  - Humoral immune response of water buffalo naturally infected with Toxocara
      vitulorum was monitored using three different antigens of this parasite in serum
      and colostrum of buffalo cows and calves. Soluble extract (Ex) and
      excretory/secretory (ES) larval antigens and perienteric fluid antigen (Pe) of
      adult T. vitulorum were used to measure the antibody levels by an indirect ELISA.
      Serum of 7-12 buffalo cows for the first 365 days and colostrum of the same
      number of buffalo cows for the first 60 days of parturition, and serum of 8-10
      buffalo calves for the first 365 days after birth were assayed. The ELISA
      detected antibodies against all three T. vitulorum antigens in the colostrum and
      serum of 100% of buffalo cows and calves examined. The highest antibody levels
      against Ex, ES and Pe antigens were detected in the buffalo cow sera during the
      perinatal period and were maintained at high levels through 300 days after
      parturition. On the other hand, colostrum antibody concentrations of all three
      antigens were highest on the first day post-parturition, but decreased sharply
      during the first 15 days. Concomitantly to the monitoring of immune response, the
      parasitic status of the calves was also evaluated. In calves, antibodies
      passively acquired were at the highest concentrations 24 h after birth and
      remained at high levels until 45 days coincidentally with the peak of T.
      vitulorum infection. The rejection of the worms by the calves occurred
      simultaneously with the decline of antibody levels, which reached their lowest
      levels between 76 and 150 days. Thereafter, probably because of the presence of
      adults/larvae stimulation, the calves acquired active immunity and the antibodies
      started to increase slightly in the serum and plateaued between the days 211 and
      365. All three antigens were detected by the serum antibodies of buffalo calves;
      however, the concentration of anti-Pe antibody was higher than anti-EX and anti
      ES, particularly after 90 days of age. By conclusion, the buffalo cows develop
      immunity and keep high levels of antibodies against T. vitulorum-Ex, ES and Pe
      antigens and these antibodies are transferred to their calves through the
      colostrum. This passively acquired immunity does not protect the calves against
      the acquisition of the infection, but these antibodies, passively or actively
      acquired, may have an important role during worm rejection by the calves and
      prevention of intestinal reinfection.

PMID- 15158558
TI  - Report in Europe of nasal myiasis by Rhinoestrus spp. in horses and donkeys:
      seasonal patterns and taxonomical considerations.
AB  - Two species of Rhinoestrus (i.e. Rhinoestrus purpureus (Brauer) and Rhinoestrus
      usbekistanicus Gan) cause nasal myiasis in horses, donkeys and zebras. In the
      past 15 years myiasis caused by R. purpureus has been reported in Egypt and by R.
      usbekistanicus in Senegal and Niger, both in horses and in donkeys. With the aim
      to investigate the presence of this myiasis in autochthonous horses and donkeys
      from southern Italy and to study the seasonal trend of larval infection, 212
      native horses were necropsied in two slaughterhouses in the Apulia region (site
      A) from January to November 2003, and 120 native horses and two donkeys in one
      slaughterhouse in Sicily (site B) from January to October 2003. Thirteen of 212
      and 5 of 120 horses examined from sites A and B, respectively, were infected by
      nasal bot fly larvae. Both donkeys examined were positive. Two hundred and
      thirteen larvae, representing all stages, were collected from the throat region,
      the turbinates and beyond the lamina cribrosa of the ethmoid bone, in the
      cerebral cavity. Third larval stages were retrieved from April to September with
      the highest mean burden in site A in May and in July in site B. The simultaneous
      presence all three larval stages at site B suggests the existence of two or more
      overlapping generations. Larvae were identified on the basis of peritreme
      structures and arrangement of the spines on the dorsal surface of the third
      segment. Some L3 collected from sites A and B presented morphological
      characteristics of both R. usbekistanicus and R. purpureus. The presence of mixed
      features on the L3 of Rhinoestrus collected from the same animals may be
      explained by the existence of a single species of Rhinoestrus presenting
      different morphotypes or of two species of Rhinoestrus which are both present in
      southern Italy since this area is midway between eastern and African countries
      where these two species have been reported.

PMID- 15158559
TI  - Comparative inter-species pharmacokinetics of phenoxyacetic acid herbicides and
      related organic acids. evidence that the dog is not a relevant species for
      evaluation of human health risk.
AB  - Phenoxyacetic acids including 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro
      2-methylphenoxyacetic acid (MCPA) are widely utilized organic acid herbicides
      that have undergone extensive toxicity and pharmacokinetic analyses. The dog is
      particularly susceptible to the toxicity of phenoxyacetic acids and related
      organic acids relative to other species. Active renal clearance mechanisms for
      organic acids are ubiquitous in mammalian species, and thus a likely mechanism
      responsible for the increased sensitivity of the dog to these agents is linked to
      a lower capacity to secrete organic acids from the kidney. Using published data
      describing the pharmacokinetics of phenoxyacetic and structurally related organic
      acids in a variety of species including humans, inter-species comparative
      pharmacokinetics were evaluated using allometic parameter scaling. For both 2,4-D
      and MCPA, the dog plasma half-life (t(1/2)) and renal clearance (Clr; mL/h) rates
      did not scale as a function of body weight across species; whereas for all other
      species evaluated, including humans, these pharmacokinetic parameters reasonably
      scaled. This exceptional response in the dog is clearly illustrated by comparing
      the plasma t(1/2) at comparable doses of 2,4-D and MCPA, across several species.
      At a dosage of 5mg/kg, in dogs, the plasma t(1/2) for 2,4-D and MCPA were
      approximately 92-106 and 63 h, respectively, which is substantially longer than
      in the rat (approximately 1 and 6 h, respectively) or in humans (12 and 11 h,
      respectively). This longer t(1/2), and slower elimination in the dog, results in
      substantially higher body burdens of these organic acids, at comparable doses,
      relative to other species. Although these results indicate the important role of
      renal transport clearance mechanisms as determinants of the clearance and
      potential toxicity outcomes of phenoxyacetic acid herbicides across several
      species, other contributing mechanisms such as reabsorption from the renal
      tubules is highly likely. These findings suggest that for new structurally
      similar organic acids, a limited comparative species (rat versus dog)
      pharmacokinetic analysis early in the toxicology evaluation process may provide
      important insight into the relevance of the dog. In summary, the substantial
      difference between the pharmacokinetics of phenoxyacetic acids and related
      organic acids in dogs relative to other species, including humans, questions the
      relevance of using dog toxicity data for the extrapolation of human health risk.

PMID- 15158560
TI  - Effects of S-adenosylmethionine on intrabiliary glutathione degradation induced
      by long-term administration of cyclosporin A in the rat.
AB  - We investigate the ability of S-adenosylmethionine (SAMe) to antagonize the
      cyclosporine A (CyA)-induced inhibition of biliary glutathione efflux induced by
      long-term administration of CyA (10 mg/kg per day-CyA(10) or 20 mg/kg per day
      CyA(20) for 4 weeks) in rats. CyA treatment reduced the liver content of total
      glutathione and caused a significant increase in the oxidized-to-reduced
      glutathione ratio and the thiobarbituric acid-reactive substances (TBARS)
      concentration. When the rats were concurrently treated with SAMe (10 mg/kg twice
      daily) and CyA, all these parameters did not significantly differ from control
      values. Treatment with CyA induced a significant increase in liver GGT activity
      that was attenuated by coadministration of SAMe. Biliary efflux of total
      glutathione was significantly reduced in animals treated with CyA. These changes
      were abolished by SAMe administration. Following inhibition of the intrabiliary
      catabolism of the tripeptide by acivicin, glutathione efflux rates increased to a
      lesser extent in animals cotreated with SAMe when compared to those receiving
      only CyA. The significant decrease in biliary efflux of oxidized glutathione
      induced by CyA was totally (S + CyA(10)) or partially (S + CyA(20)) prevented by
      coadministration of SAMe. Our observations confirm that SAMe cotreatment in rats
      antagonizes CyA-induced inhibition in the biliary efflux of glutathione and
      suggest that protection against intrabiliary glutathione degradation plays a
      major role in this protective effect.

PMID- 15158561
TI  - Rat liver glutathione S-transferase activity stimulation following acute cadmium
      or manganese intoxication.
AB  - The effect of cadmium or manganese administration on rat liver glutathione S
      transferase (GST) has been investigated. The activity of this enzyme in liver
      cytosol, where almost all the cellular activity is present, had increased by more
      than 36% 24 h after a single i.p. injection of CdCl(2) (2.5 mg kg(-1) b.w.) or
      MnCl(2) (2.0 mg kg(-1) b.w.). After shorter and longer time intervals, a lower
      enzyme activity stimulation was observed in both cases. When liver cytosol was
      incubated for 10 min with 75 microM CdCl(2) or 40 microM MnCl(2), no effect was
      observed on enzyme activity. The increase in GST following cadmium or manganese
      administration was blocked by prior administration of actinomycin D, indicative
      of a possible transcription-dependent response. The liver soluble GST from both
      control and metal-treated rats was not at all affected by Vitamin E, in the range
      of 20-300 microM. By contrast, hematin was seen to be a competitive inhibitor of
      this liver enzyme from both types of rats by using CDNB as substrate and the K(i)
      value was equal to 0.22 microM. The possibility that under the conditions used
      class alpha GST isoenzymes are affected by cadmium or manganese is discussed.

PMID- 15158562
TI  - Chromosomal aberrations, micronuclei and nuclear buds induced in human
      lymphocytes by 2,4-dichlorophenoxyacetic acid pesticide formulation.
AB  - Pesticides of worldwide application are used in agriculture in vast amounts each
      year, of which herbicides are the most prominent class. Phenoxyacetic herbicides
      constitute one of the largest groups of herbicides sold in the world. Among them,
      for many years 2,4-dichlorophenoxyacetic acid (2,4-D) has been the one most used.
      In this study we used Deherban A, a commercial formulation of 2,4-D to determine
      its possible genotoxic effect on human lymphocytes in vitro by chromosomal
      aberration analysis and micronucleus assay including the scoring of nuclear buds.
      Two different concentrations of pesticide formulation were used so that final
      concentrations of 2,4-D were 0.4 and 4 microg/ml, both in the presence and in the
      absence of the liver microsomal fraction as metabolic activator. Both
      concentrations of pesticide caused an increase in chromatid and chromosome
      breaks, number of micronuclei and number of nuclear buds. Presence of the S9 mix
      additionally elevated the number of chromatid breaks and micronuclei in treated
      lymphocytes.

PMID- 15158563
TI  - Pronounced induction of testicular PGF(2 alpha) and suppression of testosterone
      by cadmium-prevention by zinc.
AB  - In order to investigate the effects of cadmium (Cd) on testicular prostaglandin
      F(2 alpha) (PGF(2 alpha)) production, adult male Sprague-Dawley rats were exposed
      to CdCl(2) by subcutaneous injections. Dose-response as well as temporal-response
      experiments were performed, and PGF(2 alpha) levels were determined by
      radioimmunoassay (RIA). The highest cadmium dose (10 micromol/kg) caused a
      dramatic elevation of testicular PGF(2 alpha), which was established to occur 48
      h after exposure. At this point of time, cadmium-treated animals displayed PGF(2
      alpha) levels 16.7 times higher than saline-injected controls. No significant
      differences were found with the lower doses used (1 and 5 micromol/kg). In
      addition, the influence of pre-treatment with zinc (Zn) was assessed. The very
      strong stimulatory effect on PGF(2 alpha) synthesis (22.3-fold) detected after
      exposure to 20 micromol/kg cadmium, was completely absent in the group given zinc
      (1 mmol/kg) prior to cadmium exposure. Plasma testosterone concentrations were
      determined in the three experiments, and all groups with strongly elevated PGF(2
      alpha) levels showed drastically lowered concentrations of testosterone. Zinc pre
      treatment abolished not only the cadmium-induced rise in PGF(2 alpha) but also
      the testosterone reduction. Additionally, cadmium was found to inhibit the
      expression of steroidogenic acute regulatory protein (StAR), which is responsible
      for the rate-limiting step in steroidogenesis. The present findings establish
      that cadmium can cause a strong induction of testicular PGF(2 alpha) production,
      which might help to explain the well-known antisteroidogenic effect of this heavy
      metal. Such an inhibitory effect could be due to reduced levels of StAR.

PMID- 15158564
TI  - The role of reactive oxygen species in microcystin-LR-induced DNA damage.
AB  - Microcystins are cyclic heptapeptides produced by different freshwater
      cyanobacterial species such as Microcystis aeruginosa. They have been shown to
      induce DNA damage in vitro and in vivo, however, the mechanisms of their
      genotoxic activity remain unclear. With the comet assay we demonstrate that, in
      human hepatoma HepG2 cells, microcystin-LR (MCLR) induced DNA strand breaks which
      were transiently present and probably produced during the cellular repair of MCLR
      induced DNA damage. Digestion of DNA from MCLR-treated HepG2 cells with purified
      formamidopyrimidine-DNA glycosylase (Fpg), which recognizes specific oxidized
      purines, displayed a greater extent of DNA strand breaks than non-digested DNA,
      providing evidence that MCLR induced oxidation of purines. The number of DNA
      strand breaks detected after digestion with Fpg increased with time of exposure
      of the cells to MCLR, indicating that oxidized purines were not repaired. Using
      the 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluoroprobe we showed that MCLR,
      at non-cytotoxic concentrations, induced a time and dose dependent increase of
      intracellular reactive oxygen species (ROS) formation in HepG2 cells. The role of
      ROS in MCLR-induced DNA damage was further confirmed by exposing the cells to
      MCLR in the presence of different ROS scavengers. The formation of DNA strand
      breaks and oxidized purines was completely prevented by a superoxide dismutase
      mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), an iron chelator,
      deferoxamine (DFO), a precursor of glutathione (GSH) and intracellular ROS
      scavenger, N-acetyl-L-cysteine (NAC), and partly by hydroxyl radical scavengers
      dimethylsulphoxide (DMSO) and 1,3-dimethyl-2-thiourea (DMTU). The results provide
      evidence that the genotoxicity of MCLR is mediated by ROS.

PMID- 15158565
TI  - Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective
      proliferative stimulus induced by fumonisin B1.
AB  - In order to investigate the role of sphingolipid disruption in the cancer
      promoting potential of fumonisin B(1) (FB(1)) in the development of hepatocyte
      nodules, male Fischer 344 rats were subjected to cancer initiation (FB(1)
      containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2
      acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a
      secondary FB(1) dietary regimen. Sphinganine (Sa) and sphingosine (So) levels
      were measured by high performance liquid chromatography in control, surrounding
      and nodular liver tissues of the rats. The disruption of sphingolipid
      biosynthesis by the secondary FB(1) treatment in the control rats was
      significantly (P < 0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The
      nodular and surrounding Sa levels returned to baseline following FB(1) initiation
      and 2-AAF/PH promotion. When comparing the groups subjected to the secondary
      FB(1) treatment, the initiation effected by FB(1) was less (P < 0.01) sensitive
      to the accumulation of Sa in the nodular and surrounding tissues than DEN
      initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB(1)
      initiation was marginally increased in the nodules compared to the surrounding
      liver after 2-AAF/PH promotion and significantly (P < 0.05) higher with the
      secondary FB(1) treatment. Although, the FB(1)-induced hepatocyte nodules were
      not resistant to the disruption of sphingolipid biosynthesis, the nodular So
      levels were increased and might provide a selective growth stimulus possibly
      induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate
      (S1P).

PMID- 15158566
TI  - Evaluation for reliability and feasibility of the draft protocol for the enhanced
      rat 28-day subacute study (OECD Guideline 407) using androgen antagonist
      flutamide.
AB  - As part of an international validation project to establish a test protocol for
      the 'Enhanced OECD Test Guideline no. 407', a 28-day repeated dose study of
      flutamide was performed (1) to examine which of the current and/or additional
      parameters can detect endocrine effects of test chemicals most reliably and
      sensitively, (2) to investigate whether it is actually feasible to routinely
      include all additional parameters into the testing routine, and (3) to assess
      intra-laboratory variability by performing two identical studies (experiments A
      and B) in parallel using groups of five animals each per dose and sex. Groups of
      five male and five female CD(SD)IGS rats were treated by oral gavage with 0, 1,
      10 and 100 mg flutamide/kg body weight for at least 28 days. The dose level
      considered to be around the MTD (100 mg/kg) exerted the expected antiandrogenic
      effects on androgen related tissues: significant decrease of the weights of
      androgen dependent organs and the sperm count and increase in histopathological
      lesions. At the middle dose (10 mg/kg), significant decrease of prostate weight
      (ventral and dorso-lateral parts combined) was observed and it was suggested that
      weight measurement of androgen dependent organs provides the most reliable and
      sensitive endpoint with this protocol. As for the feasibility, because of many
      items in this protocol, selection should be based on the sensitivity. From our
      data, addition of weight measurement of androgen dependent organs to the items of
      the existing OECD 407 guideline might allow accurate screening for endocrine
      disruptors. At the dose level considered to be around the MTD, the findings
      achieving statistical significance in one experiment with five animals/dose/sex
      could be reproduced in the second experiment, and evaluation with the small
      groups was consistent with findings using the combined groups of 10
      animals/dose/sex. The results demonstrate that the protocol can reliably detect
      antiandrogenic effects of flutamide.

PMID- 15158567
TI  - Risk factors for Salmonella enterica subsp. enterica infection in senegalese
      broiler-chicken flocks.
AB  - Our objective was to assess the association of managerial practices, general
      hygiene and Salmonella infection in Senegalese broiler flocks. Seventy broilers
      farms were studied from January 2000 to December 2001 around Dakar. A
      questionnaire was submitted to the farmers and samples of fresh broiler droppings
      were taken. A 28.6% of the flocks were infected by Salmonella (mainly Hadar and
      Brancaster serovars). Salmonella infection of the previous flock (OR = 6.82) and
      of day-old chicks (OR = 3.73), frequent poultry farmers' visits (OR = 5.38) and
      keeping sick birds inside the farm (OR = 5.32) increased the risk of Salmonella
      infection. But, using antibiotics on day-old chicks (OR = 0.17) and a detergent
      for cleaning (OR = 0.16) decreased the risk.

PMID- 15158569
TI  - Memory decay and performance-related information bias in the reporting of scores
      by event riders.
AB  - We used data from a case-control study investigating risk factors for horse falls
      in the cross-country phase of eventing in Great Britain (GB) to examine evidence
      for memory decay and information bias. Responses to two questions obtained by
      telephone for 173 cases and 521 controls were examined for evidence of
      differential reporting according to the respondent's case-control status and
      performance in the dressage and cross-country phases of competitions. Information
      bias was found in the accuracy of reporting dressage penalty scores when analysed
      as a function of performance level (good/poor). Poor dressage performers were
      less likely to report accurate dressage scores than good performers. The accuracy
      of reporting dressage scores decreased as the time between the event and
      questionnaire completion increased, with no case-control interaction. Competitors
      who incurred cross-country jumping penalties at the event preceding the selected
      event reported their cross-country scores with less accuracy when compared with
      competitors who incurred no penalties. No information bias was found when the
      reporting of dressage and cross-country scores were analysed as a function of
      respondent category (case/control).

PMID- 15158568
TI  - Breakdown severity during a bovine tuberculosis episode as a predictor of future
      herd breakdowns in Ireland.
AB  - A retrospective cohort study of Irish cattle herds investigated whether the
      severity of a herd's bovine tuberculosis (BTB) breakdown was a predictor of the
      hazard of a future BTB breakdown in that herd. Data on 10,926 herds not having
      had BTB in 1995 (the "non-exposed" group) were obtained using a 10% random sample
      from all herds without BTB in 1995. Data on 6757 herds that had a new BTB
      breakdown in 1995 (the "exposed" group) were obtained and categorized into five
      increasing exposure-severity classes based on the total number of standard
      reactors (to the single intra-dermal comparative cervical tuberculin test)
      detected during the breakdown. Exposed herds were deemed to be free of BTB after
      they passed a 6-month check test; non-exposed herds were deemed free as of the
      date of the first negative herd-test in 1995. In the 5 years after 1995, 18% of
      the non-exposed herds had a BTB breakdown, whereas 31% of the exposed herds had a
      subsequent breakdown. Relative to the hazard for non-exposed herds, the hazard
      for the first future singleton standard reactor breakdown, was 1.6-times higher
      for exposed herds with only 1 standard reactor in 1995, and 1.8-times higher for
      those exposed herds with 4-8 standard reactors during the 1995 episode. When the
      outcome for future breakdowns was 2 or more standard reactors, the hazard ratios
      ranged from 1.6 for exposed herds with only 1 standard reactor in 1995 up to 2.9
      in exposed herds with 8 or more standard reactors during the 1995 episode. The
      latter hazard ratio varied over time, decreasing to 1.7 after 3 years of risk.
      The hazard of a future BTB breakdown increased directly with number of cattle in
      the herd, a positive history of previous BTB in the herd, and the local herd
      prevalence of BTB. The presence of confirmed BTB lesions in reactor cattle was
      not predictive of the future breakdown hazard when the effects of other factors
      were controlled.

PMID- 15158570
TI  - Characterisation of smallholder pig production in Kikuyu Division, central Kenya.
AB  - A three-phase study was conducted in high-potential farming and peri-urban area
      in Kikuyu Division central Kenya to obtain farm and management data and to
      monitor health and productivity of pigs in smallholder farms. The first phase was
      a cross-sectional study in which 87 farms (that had been selected from a total of
      179 farms using a simple random selection) were visited once and data on
      important farm and management factors were gathered using semi-structured
      questionnaires. The second phase was a pilot study that was conducted in the 87
      study farms for a period of 3 months to pretest the data-collection tools and to
      evaluate the general research methodology for the longitudinal study. The third
      phase was a prospective 12-month observational study in which health and
      productivity of pigs were monitored monthly in 76 herds that were still active
      and had participated in the previous studies. The initial voluntary enrollment
      among the eligible farms was 99%. The median farm size was 1 acre. All the farms
      kept crossbreed pigs of Large White or Landrace (median nine pigs per farm). The
      median number of sows per herd was one. Most farmers engaged in farrow-to-finish
      pig-production system and most (60%) did not keep a breeding boar. The pigs were
      stall-fed the year round. Guard rails/piglet devices were present in 22% of the
      herds. Few (8%) farmers disinfected pig pens (especially the farrowing area).
      None of the farmers reported the use of vaccination against pig diseases. Most
      farmers (84 and 96%) indicated that they controlled for mange and worm
      infestations, respectively. To control mange, 50% of the farmers used acaricides,
      34% used engine oil and 12% used both. Anthelmintics were used to control worms.
      No farmer had a particular control programme in place for both worms and mange.
      Artificial heating for piglets was not used in any of the farms. High costs of
      feeds (which were of variable qualities) lack of credit and genetically high
      quality breeding boars and diseases were ranked highly by the farmers as the main
      production constraints. Thirteen percent (11/87) of farmers withdrew during the
      pilot study; 10 farmers had sold their pigs and one had died. Thirty-three
      percent (25/76) of the farms withdrew during the longitudinal study for various
      reasons that included death of pigs (3%; 2/76) and sale of the pigs (30%; 23/76)
      mainly because of financial need.

PMID- 15158571
TI  - Health and production measures for smallholder pig production in Kikuyu Division,
      central Kenya.
AB  - A longitudinal study was carried out in Kikuyu Division (a peri-urban area in
      central Kenyan highlands) between January 1999 and December 1999 to estimate the
      baseline parameters on reproductive performance of the sow, as well as health and
      productivity of grower and preweaning pigs of smallholder herds. Data were
      collected on 155 breeding pigs, 795 grower pigs and 801 preweaning piglets in 74,
      50 and 40 smallholder herds, respectively, using record cards that were updated
      during monthly visits. The sow-level medians were: weaning-to-service interval 3
      months; interfarrowing interval 6.4 months; number of live-born piglets 9.0; and
      number of piglets weaned per litter 7.5. The piglet crude morbidity incidence
      risk was 29%. The cause-specific incidence risks for the important health
      problems encountered in preweaned piglets were diarrhea (4.3%), pruritus (17.1%),
      and skin necrosis (4.2%). The estimated crude mortality incidence risk to 8 weeks
      of age was 18.7%. The cause-specific mortality incidence risks to 8 weeks of age
      for the important causes of mortality were overlying (9.9%), savaging (2.4%),
      unviable piglets (2.0%) and unknown (1.9%). Overall, 78.8% of the total live-born
      piglet mortality occurred during the first week postpartum with 69% of these
      deaths being caused by overlying. The grower-pig crude morbidity incidence risk
      was 20% and the cause-specific incidence risks of the important health problems
      encountered were gut edema (1.3%), pruritus (21.1%), and unknown (2.3%). The
      crude mortality incidence risk was 3.8% and the important causes were gut edema
      and unknown causes (cause-specific mortality incidence risks of 1.3 and 1.6%,
      respectively). The median weight:age ratio and average daily weight gain for the
      grower pigs were 5.1 kg/month of age and 0.13 kg/day, respectively. For
      preweaning pigs, the median average daily weight gain was 0.13 g/day.

PMID- 15158572
TI  - A model of the spread of the bovine viral-diarrhoea virus within a dairy herd.
AB  - Wet BVDSim (a stochastic simulation model) was developed to study the dynamics of
      the spread of the bovine viral-diarrhoea virus (BVDV) within a dairy herd. This
      model took into account herd-management factors (common in several countries),
      which influence BVDV spread. BVDSim was designed as a discrete-entity and
      discrete-event simulation model. It relied on two processes defined at the
      individual-animal level, with interactions. The first process was a semi-Markov
      process and modelled the herd structure and dynamics (demography, herd
      management). The second process was a Markov process and modelled horizontal and
      vertical virus transmission. Because the horizontal transmission occurs by
      contacts (nose-to-nose) and indirectly, transmission varied with the separation
      of animals into subgroups. Vertical transmission resulted in birth of
      persistently infected (PI) calves. Other possible consequences of a BVDV
      infection during the pregnancy period were considered (pregnancy loss, immunity
      of calves). The outcomes of infection were modelled according to the stage of
      pregnancy at time of infection. BVDV pregnancy loss was followed either by
      culling or by a new artificial insemination depending on the modelled farmer's
      decision. Consistency of the herd dynamics in the absence of any BVDV infection
      was verified. To explore the model behaviour, the virus spread was simulated over
      10 years after the introduction of a near-calving PI heifer into a susceptible 38
      cow herd. Different dynamics of the virus spread were simulated, from early
      clearance to persistence of the virus 10 years after its introduction.
      Sensitivity of the model to the uncertainty on transmission coefficient was
      analysed. Qualitative validation consisted in comparing the bulk-milk ELISA
      results over time in a sample of herds detected with a new infection with the
      ones derived from simulations.

PMID- 15158573
TI  - A meta-analysis of the milk-production response after anthelmintic treatment in
      naturally infected adult dairy cows.
AB  - Meta-analysis was used to estimate the effects of anthelmintic treatment on milk
      production in dairy cows. The literature search included peer-reviewed journals
      (both full articles and abstracts), conference proceedings and theses and
      included documents written in English, Spanish, French, Portuguese or Italian.
      The study outcome was defined as the difference in milk production (kg/cow per
      day) between treated and untreated cows. Random effect meta-analyses were
      performed on 75 trials published between 1972 and 2002. The combined estimate
      after controlling for publication bias and/or small-study effect was of 0.35
      kg/cow per day. Significant variation among studies was detected and although
      several variables were associated with the study outcome, they did not
      significantly reduce the unexplained variability among trials. Trials reporting
      the use of endectocides had higher milk-production response compared with trials
      using older anthelmintics. Similarly, whole-herd treatment trials or trials which
      applied the treatment in mid-lactation or strategically throughout the year had
      higher response compared with calving or dry-period treatment trials. Trials
      reporting the results as total 305-day milk production had lower response
      compared with trials which measured production as daily milk weight. Primiparous
      cows trials had lower responses compared with multiparous cows trials.

PMID- 15158574
TI  - Sheep-farm risk factors for ivermectin resistance in Ostertagia circumcincta in
      Western Australia.
AB  - On-farm risk factors associated with ivermectin resistance on sheep farms in
      Western Australia were identified from data derived from a postal survey of 235
      farmers who had conducted a fecal egg-count-reduction test in 1999, 2000, or both
      years. A response of 54% was achieved. We developed a logistic-regression model.
      Contributory main effects in the final model were selling 10% more sheep in 2000
      than is the usual policy (OR = 4.00), farm purchased since 1975 (OR = 2.34), and
      number of winter flock anthelmintic treatments in the previous 5 years (OR =
      1.04). A secondary logistic-regression model assessed risk factors for farms
      selling 10% more sheep than usual in 2000; these farmers appeared less committed
      to their sheep enterprises than other farmers. These results are discussed in
      relation to current hypotheses of anthelmintic resistance. This is the first time
      that the farmer's management of the flock has been implicated in the development
      of anthelmintic resistance.

PMID- 15158575
TI  - Incidence of respiratory disorders during housing in non-weaned Charolais calves
      in cow-calf farms of Pays de la Loire (Western France).
AB  - We assessed the incidence rate of respiratory disorders during the 1999-2000
      housing period in non-weaned calves reared in a specific cow-calf farming system
      in western France, examined its variations according to age of the calf, housing
      facility and meteorological conditions, and described the different time
      distribution patterns of incident cases within the barns. Treatments for
      respiratory disorders were recorded by the farmers on a specific sheet according
      a written definition provided. A case "occurred" on a given day if the calf
      concerned was treated for respiratory disorder on this day but not in the
      previous 14 days. At the barn level, episodes of respiratory disorder were
      determined based on the time-distribution of incident cases. An episode started
      on a given day if at least one case occurred on this day in the barn concerned
      without any cases occurring in the previous 14 days. Data were suitable for
      analysis for 6813 calves, in 199 barns, located in 137 farms, where no
      metaphylactic treatment (mass treatment of ill and not-ill calves at the barn
      level) was implemented. The incidence rate of respiratory disorders was 1.89
      cases per 1000 calf-days at-risk. The proportion of reoccurrent cases was 8.6%.
      During the 1999-2000 housing period, cases occurred more frequently between 1
      November and 20 January. The incidence rate of cases peaked between 14 and 20
      days of age and was lower after 105 days of age. Large variation in incidence
      existed among barns. In one-third of the buildings, no case was observed. A
      higher incidence of cases was observed in loose-housing yards compared to tied
      cow stalls. No clear trend between daily meteorological measurements and daily
      incidence rate of cases was evidenced. A total of 11 barn-level episodes occurred
      in 9 tied-cow stalls and 229 barn-level episodes occurred in 120 loose-housing
      yards. Large variations in the characteristics of episodes (duration, incidence
      of sick calves) and in their time-distribution existed between barns.

PMID- 15158576
TI  - Dementia with Lewy bodies: a review.
AB  - The dementia with Lewy bodies (DLB) is the second major type of senile,
      degenerative dementia, after the Alzheimer disease (AD). It is characterized by
      the presence of cytoplasmic inclusions of alpha-synuclein in the cerebral cortex
      and in the nuclei of the brain stem. DLB patients frequently have complex visual
      hallucinations, depressive symptoms, Parkinsonian manifestations and cognitive
      deficits, showing important associations with the Parkinson disease and the AD.
      The DLB should be differentiated from atypical Parkinsonisms, but the
      differential diagnosis often remains difficult and unsafe. Clinical and
      neuropathological findings, as well as neuroimaging are valuable tools in
      establishing specific diagnosis of DLB. Acetylcholinesterase inhibitors, dopamine
      agonists, benzodiazepines of short or medium half-life, and antidepressants may
      be useful in the treatment of DLB, depending on the dominant symptoms of the
      given patients.

PMID- 15158578
TI  - The relationship between quality of life, Mini-Mental State Examination, and the
      Instrumental Activities of Daily Living in patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) affects the cognitive function and capacity for
      independent living of the elderly, however little is known about the measurement
      of patient's overall health-related quality of life (HRQoL) and its relationship
      to these effects. We examined the relationship between patient/caregiver-rated
      HRQoL and cognition (using the Mini-Mental State Examination (MMSE)) or
      Instrumental Activities of Daily Living (IADL). One hundred AD patients
      participating in an open-label trial of donepezil were followed for 6 months.
      Cognition and function were assessed using the MMSE (clinician-rated) and IADL
      scale (caregiver-rated). Patient QoL, as assessed by the Assessment of Quality of
      Life (AQoL) scale, was rated separately by patients and their primary caregivers.
      Mean patient-rated AQoL was 0.60, whilst caregiver-rated AQoL was 0.50. Patient
      and caregiver AQoL assessments correlated (r = 0.37, P = 0.0038) for all levels
      of disease severity. Patient-rated AQoL scores ranged from 0.52 for patients with
      severe AD, to 0.71 for patients with mild AD. Caregiver-rated AQoL scores ranged
      from 0.40 to 0.59. There were approximately linear relationships between the AQoL
      and MMSE scores (patient-rated r = 0.30, P < 0.0001; caregiver-rated r = 0.28, P
      < 0.0001), and AQoL and IADL scores (patient-rated r = 0.36, P < 0.0001;
      caregiver-rated r = 0.43, P < 0.0001). Patient self-assessment of AQoL is a
      useful instrument for measuring HRQoL in AD that displays an approximately linear
      relationship with MMSE, IADL, and caregiver-rated AQoL.

PMID- 15158577
TI  - Depression in Japanese community-dwelling elderly--prevalence and association
      with ADL and QOL.
AB  - This cross-sectional study examined the prevalence of screening-based depression
      and compared the scores of activities of daily living (ADL) and quality of life
      (QOL) between community-dwelling elderly subjects with and without depression in
      Japan. Elderly subjects aged 65 or older living in four rural towns participated
      in 2000 or 2001 (n = 5363, female 58.3%, mean (S.D.) age 74.6 (7.0) years).
      Depressive symptoms were assessed using a 15-item Geriatric Depression Scale (GDS
      15) and ADL, higher functions, and medical and social histories were assessed by
      self-report questionnaires. For assessing subjective QOL, a 100 mm visual
      analogue scale was used. One thousand seven hundred ninety-eight participants
      (33.5%, range, 32.3-34.6%) had suggestive depression using cutoff 5/6 of GDS-15.
      Subjects with depression revealed significantly lower scores for ADL and QOL than
      those without depression. Prevalence of screening-based depression was similar in
      the four different rural Japanese towns. However, the reported prevalence of
      depression varies enormously in different country. Primary physicians and
      caregivers should pay more attention to depression in the community-dwelling
      elderly population, especially below the threshold of major depression as minor
      depression or dysthymia.

PMID- 15158579
TI  - Distortion of iron status indices by acute inflammation in older hospitalized
      patients.
AB  - The relation between acute inflammation and biochemical indices of iron and
      nutritional status in older in-patients have been investigated. Thirty-nine
      consecutive patients (25 men and 14 women; median age 79 years) with acute
      inflammation episode were evaluated. C-reactive protein (CRP) > or = 3 mg/dl was
      considered to indicate acute inflammation. Iron and nutritional status were
      explored measuring hemoglobin (Hb), hematocrit (Ht), red blood cell (RBC), white
      blood cell (WBC), mean erythrocyte volume (MCV), mean corpuscular hemoglobin
      (MCH), and serum levels of iron (Fe), transferrin (T), percentage transferrin
      saturation (%TS), ferritin (SF), albumin (Alb) and pre-albumin (pre-Alb), the day
      after admission (T-basal), the day of onset of inflammation (T0), and
      successively (T5, T8-15, and T-final). CRP and WBC were significantly higher at
      T0 than T-basal (CRP: +1014%, P < 0.01; WBC: +30%, P < 0.01) but had reduced on
      days T8-15 compared to T0 (CRP: -90%, P < 0.01; WBC: -26%, P < 0.01). Fe serum
      levels fell at the beginning of the acute phase (T0: -24% versus T-basal; P <
      0.01), but had recovered at T-final (+36% versus T5; P < 0.01). T levels also
      varied significantly (P < 0.01) (T0: -16% versus T-basal; T-final: +18% versus
      T5). SF was slightly higher than normal at T-basal and increased further during
      inflammation (+41% at T5 versus T-basal) to reduce at T-final (-36% versus T5; P
      < 0.01). At T-final, pre-Alb and Alb were significantly higher than at T5 (pre
      Alb +63%, P < 0.01; Alb +20%, P < 0.05). The indices of iron status are disrupted
      in elderly patients during acute inflammation, just as they are in chronic
      inflammation, and cannot therefore be used to diagnose sideropenic anemia. The
      only variables not influenced by inflammation are MCV and %TS. Low values of
      these, associated with other symptoms of anemia, suggest sideropenic anemia,
      irrespective of the values of the other indices of iron status. With the
      appearance of inflammation, nutritional indices tend to decline as liver activity
      shifts to the production of acute phase proteins.

PMID- 15158580
TI  - Knowledge and lifestyle behaviors of healthy older adults related to modifying
      the onset of vascular dementia.
AB  - The purpose of this study was to examine the relationship between knowledge and
      practice of lifestyle behaviors in healthy older adults related to the prevention
      of vascular dementia. Data were derived from a convenience sample of 281 Canadian
      participants 55 years of age and older. Lifestyle was measured using the health
      promoting lifestyle profile (HPLP). Seven knowledge sub-scales were developed
      consistent to the HPLP. Multivariate analysis found that four independent
      variables accounted for 26% of the variance of a healthy lifestyle score and
      included those who reported a lower level of stress, indicated a higher knowledge
      of interpersonal relations, had a better general health self-assessment and
      higher medical knowledge. These Canadian results were compared with those from a
      study conducted in Australia and found to be similar. The study argues that
      health professionals and health education programs can better promote and
      increase awareness of healthy lifestyle behaviors by assisting older adults to
      apply this knowledge in their daily lives. Specifically, the study discusses
      policy and practice implications with regards to lifestyle issues relating to
      health responsibility, physical activity, spirituality, stress management,
      interpersonal relationships and nutrition.

PMID- 15158581
TI  - Catecholaminergic nerve fibers in bronchus-associated lymphoid tissue: age
      related changes.
AB  - Age-related changes of the catecholaminergic nerve fibers of the trachea,
      bronchial smooth muscle, lung capillaries and bronchus-associated lymphoid tissue
      (BALT) were studied in male Wistar rats aged 3 months (young), 12 months (adult)
      and 24 months (old/aged). Catecholamine histo- and immuno-fluorescence techniques
      were used, associated with image analysis and high pressure liquid chromatography
      with electrochemical detection of nor-epinephrine (nor-adrenaline). In young
      rats, blue-green fluorescent nerve fibers supply the trachea-bronchial smooth
      muscle and tracheal and bronchial glands. These structures are innervated by a
      delicate network of nerve fibers, being rich in varicosities. Pulmonary
      capillaries are sparsely innervated. The highest nor-epinephrine concentration
      was found in the trachea and bronchi, followed by BALT. The density and the
      pattern of noradrenergic nerve fibers of the trachea-bronchial tree or of the
      pulmonary vessels were similar in young and adult rats. In aged rats, a loss of
      noradrenergic nerve fibers, involving primarily the supply to the smooth muscle
      of the trachea-bronchial tree, was observed. Fluorescence microscopic techniques
      demonstrated a higher sensitivity than nor-epinephrine assay in detecting changes
      of the sympathetic nerve supply of the trachea-bronchial tree, pulmonary vessels
      and BALT. The possible significance of reduced noradrenergic nerve supply of the
      trachea-bronchial-pulmonary tree in aged rats is discussed.

PMID- 15158582
TI  - Antioxidative effects related to the potential anti-aging properties of the
      Chinese prescription Kangen-karyu and Carthami Flos in senescence-accelerated
      mice.
AB  - The popular oxidative stress theory predicts that enhancement of the
      antioxidative defense system to attenuate free radical-induced damage counteracts
      the aging process. We used senescence-accelerated mice (SAM) because SAM has been
      shown to suppress the antioxidative defense system and mitochondrial dysfunction
      induced by oxidative stress. We investigated the antioxidative effects of the
      Chinese prescription Kangen-karyu and its crude drug component Carthami Flos. The
      administration of Kangen-karyu extract at 100 mg/kg body weight per day for 10
      weeks inhibited generation of nitric oxide, superoxide and the hydroxyl radical
      (*OH), while Carthami Flos extract showed only *OH-scavenging activity. Diet
      supplemented with Kangen-karyu and Carthami Flos extracts enhanced the activities
      of the antioxidative enzymes superoxide dismutase in hepatic tissue and
      glutathione peroxidase in renal tissue, and reduced the hepatic lipid
      peroxidation level which increased with aging, indicating the protective action
      against oxidative stress by enhancing the antioxidative status. Hepatic and renal
      dysfunction with aging was also ameliorated by the administration of Kangen-karyu
      and Carthami Flos supplements. Furthermore, the observed antioxidative properties
      of the Chinese prescription Kangen-karyu were more evident than those of Carthami
      Flos. These findings suggest that the protective activity of Kangen-karyu against
      the oxidative tissue damages during aging may be due partly to synergistic and/or
      additive effects of its crude preparation. The present study strongly indicates
      that Kangen-karyu counteract the oxidative stress and ameliorating tissue damage
      possibly associated with aging in SAM.

PMID- 15158584
TI  - Use of hospitals at age 90. A population-based study.
AB  - People live longer than ever before, and the rapidly growing population of the
      oldest-old are increasingly frequent users of health care services. To determine
      the extent and causes of hospital care in the population aged 90, we examined the
      hospital discharge registers for the annual cohorts of Tampere residents born in
      1907-1910 at age 90. The basic population consisted of 1077 people, 20.6% of who
      were men and 79.4% women. Close on one-fifth or 18.7% of this group died during
      the year under review. During this year, 43.2% of men and 50.3% of women had been
      admitted to hospital. Men spent significantly fewer days in hospital than women:
      the mean length of stay for men was 19 days, for women 46 days. Of the 90-year
      olds, 6.7% were permanently staying in hospitals. The most common diagnoses at
      discharge were cardiovascular diseases, infections, psychiatric diseases
      including dementia, and trauma. Of those who had been admitted to hospital once
      or more within the year, 31.7% died during the follow-up time, while the figure
      for those not admitted was only 6.2%. People aged 90 are an important group of
      hospital users. In the future, hospitals need to be prepared to provide adequate
      care for the most common diseases affecting the growing population of the oldest
      old.

PMID- 15158583
TI  - Physiological and pathological age-associated changes in diurnal rhythm of energy
      expenditure in rats.
AB  - Although the idea that energy metabolism of rats decreases with age has been
      widely accepted, few studies with regard to the diurnal rhythm of energy
      expenditure have been reported. Whether age alone altered the diurnal rhythm of
      energy expenditure was examined in Sprague-Dawley (SD) rats. The same
      determination was conducted in Otsuka Long Evans Tokushima Fatty (OLETF) rats to
      examine the effect of insulin resistance and diabetes. OLETF rats were developed
      as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity.
      The characteristic features of OLETF rats are late onset of hyperglycemia at
      about 18 weeks of age, followed by insulin deficiency at about 65 weeks. Age
      associated changes in diurnal rhythm of energy expenditure were not observed in
      SD rats. In OLETF rats, the diurnal rhythm of energy expenditure with two peaks
      was observed at 8 weeks of age, while these two peaks disappeared at 24 weeks of
      age (with NIDDM). Then, the pattern of diurnal rhythm at 44 weeks of age (with
      advanced NIDDM) was resembled to that of 62 weeks of age (with insulin
      deficiency). In conclusion, we clarified the changes in diurnal rhythm of energy
      expenditure associated with the progress of diabetes, while age alone did not
      alter the diurnal rhythm.

PMID- 15158585
TI  - Immunopurification applied to the study of virus protein composition and
      encapsidation.
AB  - A protocol for obtaining small amounts of highly pure virus preparations starting
      from reduced volumes (<5 ml) of infected tissue culture supernatants is
      described. This procedure was adapted to the study of transmissible
      gastroenteritis coronavirus (TGEV) protein composition and RNA encapsidation.
      This protocol relies on virion capture by monoclonal antibodies specific for a
      virion membrane protein. These antibodies were bound to protein A-coated ELISA
      wells armed with rabbit anti-mouse IgG antibodies. As an example, the
      purification of (35)S-labelled TGEV virions was performed. The quality of virus
      preparations was assessed by quantifying common contaminating RNAs by real-time
      RT-PCR. The most critical factors influencing the purity degree are analysed and
      discussed.

PMID- 15158586
TI  - Diagnosis of Ostreid herpesvirus 1 in fixed paraffin-embedded archival samples
      using PCR and in situ hybridisation.
AB  - In 1994, some of the high mortality episodes that affected oysters cultured in
      France were associated with herpesviral infections. Through histology analysis,
      however, viral presence could only be suspected and confirmation of histological
      diagnosis by transmission electron microscopy was performed in only a few cases.
      Subsequently, the characterisation and genome sequencing of Ostreid herpesvirus 1
      (OsHV-1) made possible the development of specific molecular detection (PCR and
      in situ hybridisation (ISH)). Using both molecular tools, attempts were made to
      screen for OsHV-1 a number of fixed, paraffin-embedded oyster samples collected
      and processed in 1994. The aim was to compare these techniques and to estimate
      the accuracy of histology-based indication of viral infection. Existing DNA
      extraction protocols were adapted for oyster samples and two pairs of specific
      primers targeting small fragments (less than 200bp) were designed (C(9)/C(10) and
      B(4)/B(3)). The poor consistency observed between the results of PCR with both
      primer pairs was confirmed by statistical analysis. C(9)/C(10), which targets a
      repeated region of the OsHV-1 genome, appears to be the primer of choice for
      viral detection in archival samples. In situ hybridisation may furnish
      complementary information concerning the localisation of viral foci. Under
      certain conditions, retrospective examination of archival samples by molecular
      techniques may therefore provide valuable epidemiological data.

PMID- 15158587
TI  - Detection of HIV-1 antiretroviral resistance from patients with persistently low
      but detectable viraemia.
AB  - We modified the Abbott diagnostics HIV-1 Viroseq version 2 assay trade mark in
      order to detect the presence of HIV-1 drug resistance mutations in patients with
      viraemia below 1000 copies/ml of plasma. One hundred and forty-four patients with
      a detectable HIV-1 plasma viral load below 1000 copies/ml were selected and HIV-1
      genetic analysis carried out using a modification of the Abbott Diagnostics
      Viroseq 2.0 assay trade mark. The procedure differs from the standard protocol in
      that a nested PCR amplification step was introduced. The oligonucleotide primers
      for the first round of PCR were those supplied in the RT-PCR module of the kit.
      The nested PCR primers were primers A and H taken from the sequencing module. One
      hundred and twenty-eight out of 144 (89%) plasma samples with an HIV-1 viral load
      of less than 1000 copies/ml (ranging from 54 to 992 copies) were successfully
      sequenced. HIV-1 genotypes were obtained from 68 out of 81 (84%) samples with a
      viral load of greater than 50 but less than 300 copies/ml and 60/63 (95%) of
      samples with a viral load of greater than 300 but less than 1000 copies/ml.
      Serial dilution of a sample with a high viral load did not affect the detection
      of resistance mutations. Multiple sequencing of samples with low viral load did
      not result in detection of additional mutations, although, in one sample the
      K103N mutation was detected in 3/6 replicates while wild-type was detected in 2/6
      and a mixture of wild-type/mutant in 1/6. Samples from patients infected with
      both clade B and non-B clades of HIV-1 could be genotyped at low copy number.
      Modification of the Abbott Viroseq assay allows reproducible sequencing of the
      HIV-1 genome from patients with low, but detectable, plasma virus burden.

PMID- 15158588
TI  - Localization of infection-related epitopes on the non-structural protein 3ABC of
      foot-and-mouth disease virus and the application of tandem epitopes.
AB  - By means of overlapping peptides expressed in Escherichia coli in combination
      with Western-blotting, infection specific linear epitopes were identified on the
      non-structural protein 3ABC of FMDV. The epitopes reacted with sera from pigs or
      guinea pigs infected with different serotypes of FMDV, but not with sera from
      normal or vaccinated animals. A protein was constructed by tandem repeat of the
      epitope covering amino acid residues 141-190 on 3ABC. An ELISA based on the
      protein with tandem epitopes could be used as a diagnostic antigen for
      differentiating infected pigs from vaccinated ones.

PMID- 15158590
TI  - Generation of a DNA microarray for determination of E6 natural variants of human
      papillomavirus type 16.
AB  - Infection with high-risk types of human papillomavirus (HPV) is necessary for the
      development of cervical cancer. However, the majority of the HPV infections are
      efficiently cleared by the immune system and only a minority persist and induce
      the development of malignant lesions. Several studies provided evidence that
      intratype genetic variations are implicated in determining the clinical outcome
      of HPV infections. In this study, we describe a DNA chip based on arrayed primer
      extension (APEX) for the analysis of the natural variants of HPV16, the most
      frequently detected type in cervical cancer world-wide. We show that HPV16 E6
      variants are detected efficiently by APEX. In addition, APEX is a valid assay for
      the simultaneous detection of different HPV16 variants. Thus, it could be used
      for clinical studies aiming to analyse multiple infections with different HPV16
      subtypes. Finally, since APEX combines the advantages of dideoxy DNA sequencing
      with the high-throughput potential of the microarray, it is suitable for the
      simultaneous analysis of a number of variable regions of HPV16 genome in large
      scale studies.

PMID- 15158589
TI  - Development of a microtiter plate fluorescent assay for inhibition studies on the
      HTLV-1 and HIV-1 proteinases.
AB  - The proteinase of human T-cell leukemia virus type-1 (HTLV-1), similar to the
      proteinase of human immunodeficiency virus type-1 (HIV-1), is a potential target
      for chemotherapy, since the virus is associated with a number of human diseases.
      A microtiter plate fluorescent assay was developed for the HTLV-1 and HIV-1
      proteinases for direct comparison of the inhibition profiles of the enzymes. It
      was established that, except for Indinavir, none of the inhibitors designed
      against the HIV-1 proteinase were able to inhibit the HTLV-1 proteinase in the
      studied concentration range, while two reduced peptide bond-containing peptides
      having the sequence of HTLV-1 cleavage sites were inhibitors of the HTLV-1
      proteinase. One of these was potent enough to be used for active site titration
      of the HTLV-1 proteinase.

PMID- 15158591
TI  - Differential amplification and quantitation of Marek's disease viruses using real
      time polymerase chain reaction.
AB  - Quantitative real-time PCR (qPCR) assays for the three serotypes of Marek's
      disease virus (MDV) have been developed. An internal control qPCR assay that
      detects chicken alpha2 (VI) collagen gene was also developed to allow
      quantitation of MDV. To reduce costs and time, the assays for MDV1 and the
      internal control were combined into a duplex assay. The sensitivity, specificity,
      precision, and reproducibility of each assay are reported. The MDV qPCR assays
      were specific to their target gene when compared using Australian field and
      vaccine strains of MDV and 10-100-fold more sensitive than standard PCR. Using
      DNA from infected spleen tissue, the lower limit of detection of total DNA (viral
      and host combined) was 0.025 ng for the MDV1 and collagen assays, and 0.25 ng for
      the HVT and MDV2 assays. All assays were found to be highly reproducible for Ct
      values, but less so for calculated concentrations. MDV1 and HVT were quantitated
      in spleen tissue of twenty experimentally infected chickens 7-35 days after
      infection. The relative abundance of MDV1 exhibited a clear peak at day 14 post
      infection, whereas HVT displayed an increasing trend over the 35 days post
      infection. The duplex assay was optimized such that it was able to accurately
      quantitate MDV1 in samples of very high, medium, and very low relative abundance
      of MDV1. These qPCR assays will be useful for reliable differentiation and
      quantitation of MDV for a range of research and industry applications.

PMID- 15158592
TI  - Quantitation of MLV-based retroviral vectors using real-time RT-PCR.
AB  - Murine leukaemia virus-based vectors quantitation is a time consuming process
      that can take up to five days. In order to reduce this time a real-time RT-PCR
      was developed. This method quantifies vectors without an RNA extraction step,
      using AMV reverse transcriptase and LightCycler technology. Besides a low
      quantitation time, this method has the advantages of using a plasmid DNA standard
      curve with good reproducibility, and of having a high sensitivity (3 x 10(2)
      particles/microl) as well as an excellent intra- and inter-assay reproducibility.
      Although the method described quantifies vector particles with RNA whether these
      particles are infectious or not, it is possible to use it to determine infectious
      particles concentration after the establishment of a correlation between
      particles with RNA and infectious particles, for a given set of conditions. This
      method can also be used to study vector stability by comparison of infectious
      particles, total particles and particles with RNA.

PMID- 15158593
TI  - Herpes simplex virus type-2 specific glycoprotein G-2 immunomagnetically captured
      from HEp-2 infected tissue culture extracts.
AB  - Monoclonal antibody H1206 anti-HSV-2 gG-2 bound to tosylactivated paramagnetic
      Dynabeads (Dynal) has been used to isolate HSV-2 type-specific gG-2 from
      solubilized HEp-2 HSV-2 infected cell extracts. The immunomagnetically captured
      type-specific glycoprotein reacted strongly with monoclonal antibody H1206 and
      demonstrated a single band with apparent molecular weight of 100000 (100 kDa) and
      a doublet band with an apparent molecular weight of 60000-64000 (60-64 kDa). We
      observed the same exact banding pattern when monoclonal H1206 was immunoblotted
      with Helix pomatia lectin purified HSV-2 gG-2. The immunomagnetically purified gG
      2 was unreactive to monoclonal antibody H1379 anti-HSV-1 gG-1 and four human HSV
      antibody negative sera. In addition, 20 human HSV antibody positive sera obtained
      from the Centers for Disease Control (CDC), Atlanta, GA, were used for the
      evaluation of our methodology. Immunoblotting of the human HSV antibody positive
      samples were in agreement with the CDC HSV serological designation. Sera
      characterized by reactivity to the immunomagnetically purified gG-2 in
      conjunction with Western blot has the potential to be used as a confirmatory
      serological test or to determine the accuracy of clinical serological
      immunoassays used to determine HSV-2 seropositivity.

PMID- 15158594
TI  - Characterization and expression of the pseudorabies virus early gene UL54.
AB  - Pseudorabies virus (PRV) is an alphaherpesvirus, and its gene organization and
      regulation are similar to the well-characterized human simplex virus (HSV).
      Sequence analysis of the complete coding region of PRV UL54 gene revealed that
      the UL54 gene consisted of 1092 nucleotides encoding a protein of 363 amino acids
      and the gene showed homology to HSV immediate-early protein ICP27. Detection of
      the UL54 transcript in infected cells by reverse transcription-polymerase chain
      reaction (RT-PCR) demonstrated that the UL54 gene belonged to the early kinetic
      class based on sensitivity to cycloheximide and insensitivity to phosphonoacetic
      acid (PAA). To study the structure and function of UL54 protein, this gene was
      subcloned on Escherichia coli expression vector pET28b for overexpression, and
      the expressed product was applied to generate specific antibody against UL54
      protein. The specificity of the mouse immuneserum was confirmed by its ability to
      react with a 40kDa viral protein present in the PRV infected cells in Western
      immunblotting assay, detected as early as 4h after infection. In addition,
      immunoperoxidasing staining of PRV infected cells undertaken with this antibody
      demonstrated mainly nuclear staining pattern. Furthermore, the RNA binding
      potential of UL54 protein was demonstrated by its binding activity to poly(G) RNA
      homopolymer in Northwestern blotting assay.

PMID- 15158595
TI  - Analytical performance of several classical swine fever laboratory diagnostic
      techniques on live animals for detection of infection.
AB  - The diagnostic properties of several assays on live animals were studied using
      data from different experiments. These experiments involved 128 classical swine
      fever virus (CSFV) infected pigs (weaner pigs, fatteners and sows). Since all
      pigs in the study were infected with CSFV, only the proportion of test positive
      results and the time until a test positive result is obtained were evaluated. The
      RT-nPCR detected the highest proportion of infected pigs (98.9%), whereas the
      Antigen ELISA gave the worst detection results (74.7%). Within the group of test
      positive animals, infection was detected earliest using the leukocyte count and
      latest using Antigen ELISA. Using the virus neutralisation test, antibodies
      against CSFV were detectable on average 7.6 days after the onset of viraemia in
      virus isolation in whole blood. Using survival analysis, the time until the first
      positive diagnosis and the proportion of detected animals were combined in one
      test. Results showed that RT-nPCR performed significantly better than either
      virus isolation in different blood fractions or antigen ELISA. It is concluded
      that the RT-nPCR technique is the best diagnostic tool available for early
      detection of a classical swine fever infection.

PMID- 15158597
TI  - Application of real-time RT-PCR for the quantitation and competitive replication
      study of H5 and H7 subtype avian influenza virus.
AB  - Avian influenza (AI) viruses are endemic in wild birds and if transmitted to
      poultry can cause serious economic losses. In the study of AI, the quantitation
      of virus shed from infected birds is valuable in pathogenesis studies and to
      determine the effectiveness of vaccines, and is performed routinely by
      cultivation of virus containing samples using embryonating chicken eggs (ECE) and
      expressed by 50% egg infectious dose (EID(50)). Although, this assay is accurate
      and is the standard test for infectious virus titration, the method is laborious,
      requires a large number of ECE, and takes at least 7 days to determine results.
      In this study, a one-tube hydrolysis fluorescent probe based real-time RT-PCR
      (RRT-PCR) was applied for the quantitation of AI virus and compared with
      conventional virus titration method. A strong positive correlation was observed
      between the amount of RNA determined by quantitative RRT-PCR and the EID(50)s
      determined by conventional methods. This RRT-PCR test was further applied in the
      study of competitive replication of co-infected H5 and H7 subtype viruses in
      chickens. Using hemagglutinin subtype specific probes, we were able to determine
      the amount of individual subtype virus, which could not have easily been done
      with conventional methods. This RRT-PCR based quantitation of AI virus, which is
      specific, sensitive, easy to perform, and rapid, will be useful for virological,
      pathogenesis, and protection studies.

PMID- 15158596
TI  - Quantitation of canine coronavirus RNA in the faeces of dogs by TaqMan RT-PCR.
AB  - A TaqMan fluorogenic reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay was developed for the detection and quantitation of canine coronavirus
      (CCoV) RNA in the faeces of naturally or experimentally infected dogs. The CCoV
      fluorogenic RT-PCR assay, which targeted the ORF5 (M gene), was more sensitive
      than a conventional RT-PCR assay targeting the same gene, showing a detection
      limit of 10 copies of CCoV standard RNA, and was linear from 10 to 10(8) copies,
      allowing quantitation of samples with a wide range of CCoV RNA loads. A total of
      78 faecal samples of diarrhoeic dogs were tested simultaneously by conventional
      and fluorogenic RT-PCR: 29 were negative by both techniques, whereas 27 tested
      positive by conventional RT-PCR and 48 by the established CCoV fluorogenic assay.
      One sample, which was positive by conventional RT-PCR, gave no signal in the
      fluorogenic assay. In addition, by the fluorogenic assay CCoV shedding in the
      faecal samples of an experimentally infected dog was monitored for 28 days. The
      high sensitivity, simplicity and reproducibility of the CCoV fluorogenic RT-PCR
      assay, combined with its wide dynamic range and high throughput, make this method
      especially suitable for efficacy trials on CCoV vaccines.

PMID- 15158598
TI  - Phage display of the Equine arteritis virus nsp1 ZF domain and examination of its
      metal interactions.
AB  - A putative zinc finger (ZF) domain in the Equine arteritis virus (EAV) nsp1
      protein was described recently to be required for viral transcription. The nsp1
      ZF (50 aa) was expressed on the surface of M13KE gIII phage, fused to the N
      terminus of the phage pIII protein. To evaluate the functionality of the ZF
      domain, a binding assay was developed, based on the use of immobilized Ni(2+)
      ions (Ni-NTA). Phages displaying ZF bound significantly better to Ni-NTA than did
      phages displaying negative-control peptides, which also contained metal
      coordinating residues. Also, binding of ZF-displaying phages could be inhibited
      by an anti-nsp1 serum, or by mutation of residues predicted to be important for
      zinc coordination. Finally, binding was abolished by low concentrations (0.1%)
      Tween 20, and rescued by including Zn(2+), Ni(2+) or Cu(2+), but not Mg(2+), in
      the binding buffer, suggesting that formation of secondary structure was involved
      in binding of the ZF to Ni-NTA. These findings provide the first experimental
      evidence that the putative nsp1 ZF domain can coordinate divalent metal ions, and
      that this property is associated with the secondary structure of the domain. The
      Ni-NTA binding assay developed in the present study may have general applications
      in the study of other ZF domains.

PMID- 15158599
TI  - A non-isotopic method for the determination of activity of the thermostable NAD
      dependent DNA ligase from Thermus thermophilus HB8.
AB  - A simple and accurate method for determination of enzymatic activity of the NAD
      dependent DNA ligase of Thermus thermophilus HB8 has been developed that requires
      no radiolabeled substrates. lambda-DNA digested with BstEII provides two
      substrate DNA molecules (fragments 1 and 4) containing 12 base pair cohesive ends
      that are stably annealed at the assay temperature of 45 degrees C. One cohesive
      end unit is defined as the amount of enzyme required to achieve 50% ligation of
      fragment 1 in 15 min at 45 degrees C. Percent ligation is determined by analysis
      of reaction products, produced in reactions containing serial dilutions of
      enzyme, separated by agarose gel electrophoresis and photographed using a digital
      imaging device. Imaging software quantifies the amounts of fragment 1 and non
      substrate fragment 7 present in the each lane (reaction). The latter is used to
      normalize the amount of fragment 1. This normalization process corrects for
      variations in sample loading, electrophoretic artifacts, and optical distortion
      of the gel image. A negative control containing no enzyme allows calculation of
      percent substrate ligated into product. Unit activity is then calculated from a
      dose-response curve in which percent of fragment 1 ligated is plotted against the
      log(10) of the enzyme dilution factor.

PMID- 15158600
TI  - Evaluation of a prototype HCV NS5b assay for typing strains of hepatitis C virus
      isolated from Tunisian haemodialysis patients.
AB  - Hepatitis C virus (HCV) strains isolated from 68 haemodialysis Tunisian patients
      exhibiting chronic infection were genotyped targeting the NS5b region of the HCV
      genome using a prototype assay developed by Bayer HealthCare-Diagnostics (TRUGENE
      NS5b HCV). The overall results were compared to those obtained with another assay
      of the same company based on sequencing of the 5' non-coding region (TRUGENE HCV
      5'NC genotyping kit). All strains could be typed by the 5'NC typing kit, but only
      62 (91; 2%) by the NS5b prototype assay. All the 62 strains typed by both methods
      exhibited the same pattern at the type level: 57 were type 1, 3 were type 2, and
      2 were type 4. At the subtype level, eight strains that gave undetermined results
      by the 5'NC kit were successfully typed by the NS5b kit; eight additional strains
      exhibited discrepant results. The overall agreement between the two assays was
      74.2% at the subtype level. In conclusion, the NS5b region appears to be much
      more accurate than the 5'NC region to subtype HCV strains, especially in those
      isolated from patients attending haemodialysis centres where the subtype
      distribution suggests frequent nosocomial transmissions.

PMID- 15158601
TI  - Distinguishing hepatitis B virus (HBV) genotype D from non-D by a simple PCR.
AB  - Different HBV genotypes have characteristic geographical distribution, which is
      important epidemiologically. HBV strains have been classified into eight
      different genotypes (A-H) on the basis of >8% differences in the entire genomic
      sequence. Genotypes A and D are predominant in Europe, Africa, and the USA,
      genotypes B and C are restricted to East Asia, genotype E is found in Africa, and
      genotype F is found in indigenous populations in Central and South America.
      Genotype D is prevalent in the Turkish population. HBV genotype D shows a 33-bp
      deletion in the pre-S1 region that accounts for their smaller genomic size (3182
      bp). This deletion can be used to facilitate the identification of genotype D. A
      primer in the pre-S1 region was designed to discriminate genotype D from non-D by
      PCR. Sixty genotype D (40 acute and 20 chronic) and 4 genotype A sera identified
      by restriction fragment length polymorphism (RFLP) were included in the study.
      Using this simple PCR method, all genotype D sera were identified correctly and
      the test was able to detect HBV DNA at 1000 genomes per ml. An advantage of this
      method is that it can differentiate in a mixture of genotypes (genotype D from
      non-D) provided that one isn't present below 1 x 10(4) copies/ml. In conclusion
      this method is rapid (approximately 5h) and it will contribute to the
      epidemiological study of HBV in high prevalence areas of genotype D. It can also
      differentiate between genotype D from non-D in cases of co-infection.

PMID- 15158602
TI  - Inhibition of EGFP expression by siRNA in EGFP-stably expressing Huh-7 cells.
AB  - The RNA interference (RNAi) is a powerful tool to silence gene expression post
      transcriptionally, and causes the degradation of an mRNA containing the same
      sequence. In this present study, an alternative approach was used to in vitro
      synthesize enhanced green fluorescent protein (EGFP) specific short interfering
      RNA (siRNA) using T7 RNA polymerase, and a pEGFP-N1 transfected, human hepatoma
      cell line Huh-7 derived Huh-7-N cell clone was established. When introduced the
      siRNA into the EGFP expressing Huh-7-N cells, the EGFP specific siRNA was able to
      specifically inhibit the expression of EGFP in Huh-7-N. In comparison with that
      in wild-type Huh-7 or that in Huh-7 co-transfected with pEGFP-N1, the inhibition
      of EGFP specific siRNA in Huh-7-N cells is more significant and repeatable. It is
      concluded that a cell clone Huh-7-N, which stably expresses EGFP, has been
      established, and the in vitro synthesized EGFP siRNA can be used in silencing the
      EGFP gene expression. This Huh-7-N/EGFP specific siRNA system has been proved
      reliable and convenient, and can also be applied widely as control in other RNA
      interference studies.

PMID- 15158603
TI  - Virus inactivation by nucleic acid extraction reagents.
AB  - Many assume that common methods to extract viral nucleic acids are able to render
      a sample non-infectious. It may be that inactivation of infectious virus is
      incomplete during viral nucleic acid extraction methods. Accordingly, two common
      viral nucleic acid extraction techniques were evaluated for the ability to
      inactivate high viral titer specimens. In particular, the potential for TRIzol LS
      Reagent (Invitrogen Corp., Carlsbad, CA) and AVL Buffer (Qiagen, Valencia, CA)
      were examined to render suspensions of alphaviruses, flaviviruses, filoviruses
      and a bunyavirus non-infectious to tissue culture assay. The dilution series for
      both extraction reagents consistently caused cell death through a 100-fold
      dilution. Except for the DEN subtype 4 positive control, all viruses had titers
      of at least 10(6)pfu/ml. No plaques were detected in any extraction reagent plus
      virus combination in this study, therefore, the extraction reagents appeared to
      inactivate completely each of the high-titer viruses used in this study. These
      results support the reliance upon either TRIzol LS Reagent or AVL Buffer to
      render clinical or environmental samples non-infectious, which has implications
      for the handling and processing of samples under austere field conditions and low
      level containment.

PMID- 15158604
TI  - Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory
      and autoimmune diseases.
AB  - Commensal microflora (normal microflora, indigenous microbiota) consists of those
      micro-organisms, which are present on body surfaces covered by epithelial cells
      and are exposed to the external environment (gastrointestinal and respiratory
      tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin
      surfaces exceeds the number of cells forming human body. Commensal bacteria co
      evolved with their hosts, however, under specific conditions they are able to
      overcome protective host responses and exert pathologic effects. Resident
      bacteria form complex ecosystems, whose diversity is enormous. The most abundant
      microflora is present in the distal parts of the gut; the majority of the
      intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal
      bacteria cannot be cultured by conventional microbiological techniques. Molecular
      biological methods help in analysing the structural and functional complexity of
      the microflora and in identifying its components. Resident microflora contains a
      number of components able to activate innate and adaptive immunity. Unlimited
      immune activation in response to signals from commensal bacteria could pose the
      risk of inflammation; immune responses to mucosal microbiota therefore require a
      precise regulatory control. The mucosal immune system has developed specialised
      regulatory, anti-inflammatory mechanisms for eliminating or tolerating non
      dangerous, food and airborne antigens and commensal micro-organisms (oral,
      mucosal tolerance). However, at the same time the mucosal immune system must
      provide local defense mechanisms against environmental threats (e.g. invading
      pathogens). This important requirement is fulfilled by several mechanisms of
      mucosal immunity: strongly developed innate defense mechanisms ensuring
      appropriate function of the mucosal barrier, existence of unique types of
      lymphocytes and their products, transport of polymeric immunoglobulins through
      epithelial cells into secretions (sIgA) and migration and homing of cells
      originating from the mucosal organised tissues in mucosae and exocrine glands.
      The important role of commensal bacteria in development of optimally functioning
      mucosal immune system was demonstrated in germ-free animals (using
      gnotobiological techniques). Involvement of commensal microflora and its
      components with strong immunoactivating properties (e.g. LPS, peptidoglycans,
      superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various
      complex, multifactorial and multigenic diseases, including inflammatory bowel
      diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy,
      multiorgan failure, colon cancer has been recently suggested. Animal models of
      human diseases reared in defined gnotobiotic conditions are helping to elucidate
      the aetiology of these frequent disorders. An improved understanding of commensal
      bacteria-host interactions employing germ-free animal models with selective
      colonisation strategies combined with modern molecular techniques could bring new
      insights into the mechanisms of mucosal immunity and also into pathogenetic
      mechanisms of several infectious, inflammatory, autoimmune and neoplastic
      diseases. Regulation of microflora composition (e.g. by probiotics and
      prebiotics) offers the possibility to influence the development of mucosal and
      systemic immunity but it can play a role also in prevention and treatment of some
      diseases.

PMID- 15158605
TI  - Antigen presentation by the endothelium: a green light for antigen-specific T
      cell trafficking?
AB  - The functional consequences of recognition of antigen displayed by the
      endothelium during T cell extravasation in the development of an immune response
      have been a matter of debate for a long time. Most investigations have focused on
      the induction of proliferative responses and cytokine production by T cells. In
      parallel, endothelial cells have been shown to express costimulatory molecules
      with positive and negative regulatory effects on T cell responses. Recent studies
      have provided an alternative view of the antigen presenting cell function of
      endothelial cells, suggesting that cognate recognition of the endothelium by
      trafficking T cells is a key event in selecting the migration of antigen-specific
      lymphocytes into the site of inflammation.

PMID- 15158606
TI  - Induction of cellular immune response and anti-Salmonella enterica serovar typhi
      bactericidal antibodies in healthy volunteers by immunization with a vaccine
      candidate against typhoid fever.
AB  - Typhoid fever remains a serious public health problem. We have developed a
      vaccine from Salmonella enterica serovar typhi (S. typhi) outer-membrane proteins
      (OMPs) known as porins. A single subcutaneous dose of 10 microg of porins induced
      a five-fold (P = 0.05) seroconversion index consisting of IgM and IgG at 7 and 15
      days after vaccination as well as the production of IgG1 and IgG2 isotypes. The
      porins-based vaccine induced a two-fold increase (P = 0.05) in bactericidal
      titres in volunteers, whom also developed a T-cell response characterized by the
      production of interferon-gamma (INF-gamma). Side effects after vaccination were
      mild and transient. The data showed that our S. typhi porins-based candidate
      vaccine is safe and immunogenic in healthy humans.

PMID- 15158607
TI  - Location of the epitope for an anti-CD8alpha antibody 53.6.7 which enhances
      CD8alpha-MHC class I interaction indicates antibody stabilization of a higher
      affinity CD8 conformation.
AB  - MHC class I tetramers are widely used, usually in combination with an antibody to
      CD8, to detect antigen specific T cells. Some anti-CD8alpha antibodies block the
      interaction of murine MHC class I tetramers with CD8 T cells, while others such
      as 53.6.7, enhance. To understand the molecular basis for this effect, we mapped
      the epitope for the enhancing antibody 53.6.7 and three other blocking antibodies
      using a panel of murine CD8alpha (Lyt-2) mutants expressed on COS-7
      transfectants. Mutations in residues that contact MHC class I affected binding of
      the blocking antibodies. In contrast, antibody 53.6.7 was affected by a mutation
      in the residue T81A located on the D-E loop. In the cocrystal of CD8alphaalpha
      with MHC class I, two different complexes (A and B) were observed, indicating the
      existence of different CD8 conformations. The T81 residue does not make contact
      with MHC class I in either complex, however, neighboring residues in the D-E loop
      make very different contacts in the two different complexes. The most likely
      explanation for antibody enhancement of tetramer bindings is that binding of
      53.6.7 to CD8alphabeta stabilizes a conformation with a higher affinity for
      interaction with MHC class I and suggests that the CD8 binding site is flexible.

PMID- 15158609
TI  - Phagocytosis of M. paratuberculosis fails to activate expression of NADH
      dehydrogenase and nucleolin-related protein in bovine macrophages.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is a
      facultative intracellular bacterium and causal agent of Johne's disease in
      cattle. Following phagocytosis, M. paratuberculosis resides and replicates in
      macrophage phagosomes that fail to mature. Differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) was used as a high throughput
      initial screen to begin to test the hypothesis that macrophage gene expression
      patterns would be differentially affected by M. paratuberculosis when compared to
      readily degraded bacteria or non-degradable latex beads. Gene expression profiles
      from immortalized bovine macrophage cells (BOMAC) exposed to M. paratuberculosis
      were compared to gene expression profiles for BOMAC cells exposed to Escherichia
      coli, latex beads or PBS. Amplicons representing genes specifically activated or
      repressed during M. paratuberculosis phagocytosis were cloned for further
      investigation. Northern blot hybridizations preformed using DDRT-PCR-derived
      amplicons 3-1-4, 5-2-10, 5-4-2 and 4-1-6 confirmed stimuli dependent differential
      gene expression. Expression pattern observed for amplicon 3-1-4 represents genes
      that are up-regulated following phagocytosis of E. coli or latex beads, but not
      M. paratuberculosis. Amplicon 5-2-10 exhibited a pattern of expression
      representative of genes that are up-regulated strongly following phagocytosis of
      E. coli or latex beads but only moderately following M. paratuberculosis
      phagocytosis. Expression pattern of the gene for amplicon 5-4-2 was
      representative of genes that are specifically suppressed following M.
      paratuberculosis phagocytosis, while the amplicon 4-1-6 gene expression pattern
      represented genes that are generally suppressed following phagocytosis of any of
      the three stimuli. DNA sequencing and Genbank database analysis of these
      amplicons revealed that amplicon 3-1-4, whose expression failed to activate
      following M. paratuberculosis phagocytosis, had high levels of similarity to a
      Rattus norvegicus nucleolin-related protein (NRP). Amplicon 5-2-10, which
      increased expression moderately following M. paratuberculosis phagocytosis, was a
      near perfect match to bovine nicotinamide adenine dinucleotide dehydrogenase
      (FNADH dehydrogenase) subunit 1 (ND1). Failure to activate these two genes at
      levels observed following phagocytosis of either E. coli or latex beads may
      uncover new mechanisms for the survival of M. paratuberculosis within bovine
      macrophage cells.

PMID- 15158608
TI  - Monoclonal antibodies recognizing EVETPIRN epitope of influenza A virus M2
      protein could protect mice from lethal influenza A virus challenge.
AB  - Based on the fact that the 24 amino acid extracellular domain of M2 protein (M2e)
      is nearly invariant in all influenza A strains, several different M2e vaccine
      constructs and vaccination modalities have been developed by others and us.
      Although most of these vaccines could induce efficient and broad-spectrum
      immunity inhibiting influenza A virus infection in mice model, information of the
      refined protective epitope on M2e was scarce. In this paper, two M2e specific
      monoclonal antibodies (mAbs) conferring protective immunity in vivo were
      reported, which in passive administration could protect 75% mice from five LD(50)
      (50% lethal dose) challenge of influenza virus A/PR/8/34. In addition, higher M2e
      specific antibody titer (over 1:1600) could be detected after 12h of
      intraperitoneal passive administration in mice sera. Peptide mapping assay
      indicated that both mAbs strongly interacted with N-terminus and middle part
      peptides of M2e (NM2, aa2-12; MM2, aa8-18), but not with the C-terminus peptide
      (CM2, aa13-24). More importantly, M2e specific mAbs could recognize EVETPIRN (aa6
      13) peptide, which were the overlapping region of NM2 and MM2 peptide and the
      neighboring amino acid residues. In contrast, M2e domain that was deleted EVETPIR
      sequence could not be recognized by either mAb in immunoblotting assay. All these
      results indicated that the epitope EVETPIRN (aa6-13) on M2e could be responsible
      for the induction of the protective immunity.

PMID- 15158610
TI  - Down-regulatory effect of N-chlorotaurine on tryptophan degradation and neopterin
      production in human PBMC.
AB  - N-Chlorotaurine (NCT) plays an important role in the human defense system as a
      main component of long-lived oxidants, and shows bactericidal, fungicidal, and
      virucidal activity. Besides this role, NCT seems to act regulatory on
      immunocompetent cells by altering cytokine production. NCT inhibited nitric
      oxide, TNF-alpha, and prostaglandin E(2) (PGE(2)) production in activated rodent
      macrophages, and suppressed superoxide anion, IL-6, and IL-8 formation in human
      polymorphonuclear leukocytes. In this study, the influence of NCT on the
      production of neopterin and the activation of the enzyme indoleamine-2,3
      dioxygenase (IDO) was investigated in human peripheral blood mononuclear cells
      (PBMC). Both events are well established to be triggered by IFN-gamma and
      therefore related to Th1-type immune activation. Mitogen-induced neopterin
      production as well as tryptophan degradation were drastically reduced upon
      addition of NCT. Results fit in the concept of a reduction of pro-inflammatory
      cytokines by this compound. In contrast to earlier results, where NCT was
      suggested to act primarily down-regulatory on Th2 cells, we propose also a strong
      suppressive effect of NCT on Th1-type immunity.

PMID- 15158611
TI  - Cross-linking of CD40 using anti-CD40 antibody, 5C11, has different effects on
      XG2 multiple myeloma cells.
AB  - A multiple myeloma (MM) cell line, XG2, has high-level expression of CD40, a
      tumor necrosis factor receptor (TNFR) family member. CD40 is present on the
      surfaces of a large variety of cells, including B cells, endothelial cells,
      dendritic cells and some carcinoma cells, and delivers signals regulating diverse
      cellular responses, such as proliferation, differentiation, growth suppression,
      cell death. In this research, we study the effects of cross-linking of CD40 on
      myeloma cells using different concentrations of anti-CD40 monoclonal antibody
      (mAb), 5C11. We found that low concentrations of 5C11 induced proliferation of
      XG2, while high concentrations of 5C11 resulted in homotypic aggregation of XG2,
      and strongly suppression of its proliferation and apoptosis after 24 h of
      treatment. These dose-dependent effects of 5C11 were verified by flow cytometry,
      Western blotting and immunoprecipitation. Autocrine or paracrine induction of IL
      6, and up-regulation of membrane TNF and phosphorylation of TNFR1 may partially
      explain the contradictory biological effects of CD40 cross-linking on XG2 by anti
      CD40 mAb.

PMID- 15158612
TI  - The spectrum of lymphoid subsets preferentially recruited into the liver reflects
      that of resident populations.
AB  - Intrahepatic lymphocytes (IHL) differ phenotypically from cells found in the
      peripheral blood or in lymphoid organs. The liver contains T-cells that are also
      found in lymphoid organs but a higher proportion of these T-cells compared to
      those in lymphoid organs express activation or memory markers and very few naive
      T-cells are present within the liver. Furthermore, subsets such as NK and NK T
      cells, which are detected at comparably lower levels within the lymphoid organs
      are increased within the liver. To investigate whether a preferential recruitment
      of certain lymphoid subsets from the circulation contributes to the composition
      of intrahepatic lymphocytes, we compared their frequency in the liver with their
      organ tropisms. CFSE-labeled murine lymphoid cells were injected intravenously
      and their distribution within liver and spleen was analyzed after 24 h.
      Especially CD45RB(low) memory T-cells, NK and NK T-cells, which are also present
      at high proportions within IHL, became predominantly recruited into the liver. In
      contrast, subsets such as naive CD62L(high) T-cells and B-cells, which are
      predominantly represented within the lymphoid organs, preferentially migrated
      into the spleen. These findings indicate that the pattern of migratory
      preferences reflects the representation of various subsets within the
      intrahepatic lymphocytes surprisingly well, suggesting that the composition of
      intrahepatic lymphocytes is largely shaped by the dynamics of entry and exit of
      cells into the organ.

PMID- 15158613
TI  - CD44-chondroitin sulfate interactions mediate leukocyte rolling under
      physiological flow conditions.
AB  - CD44 on leukocytes binds to its glycosaminoglycan (GAG) ligand, hyaluronic acid,
      and mediates the rolling of leukocytes on vascular endothelial cells. We
      previously reported that the recombinant CD44 protein binds to other GAGs,
      including chondroitin sulfates (CS), although the physiological significance of
      this interaction has remained unclear. Here we report that the CD44 expressed on
      mouse lymphoma BW5147 cells supports cell binding to immobilized CS under static
      conditions and mediates cell rolling in CS-coated glass capillary tubes under
      shear stresses ranging from 0.5 to 1.5 dyn/cm(2), which is within the
      physiological range of forces in venules. Both interactions were completely
      inhibited by pretreating the cells with an anti-CD44 antibody or by pretreating
      the CS with chondroitinase ABC, but not hyaluronidase. To address the role of the
      CD44-CS interaction in vivo, we examined the tissue localization of the CS that
      interacts with CD44. Interestingly, a recombinant CD44 fusion protein bound to
      hepatic sinuosoidal endothelial cells where CS was also expressed, as assessed by
      immunohistochemistry. These findings support the involvement of the CD44-CS
      interaction in the primary adhesion of lymphocytes to endothelial cells and raise
      the possibility that this interaction plays a role in the capture of CD44
      positive cells, such as activated T cells and certain tumor cells, by the hepatic
      sinusoidal vasculature.

PMID- 15158614
TI  - Erythroid cells in immunoregulation: characterization of a novel suppressor
      factor.
AB  - Nucleated erythroid cells (EC) have been previously reported to possess a potent
      natural suppressor (NS) activity for B-cell responses. In this study, we
      demonstrate that murine EC are able to reduce not only lipopolysaccharide (LPS)
      driven B-cell proliferation, but also proliferative and cytotoxic T-cell
      responses generated in a primary allogeneic mixed lymphocyte culture (MLC); and
      that a soluble low molecular weight factor may be involved in such EC-derived
      immunoregulation. In addition, the erythroid cell-derived suppressor factor (ESF)
      was found to be capable of effectively reducing the allergen-driven proliferation
      of peripheral blood mononuclear cells (PBMC) isolated from allergic patients.
      From the data presented herein, it appears that ESF is heat-stable (80 degrees C
      for 20 min) and has molecular weight (MW) lower or close to 0.5 kDa. ESF activity
      is resistant to both enzyme (trypsin plus chymotrypsin) proteolysis and action of
      the enzymes such as lipase and phospholipase C. On the other hand, ESF is
      effectively inactivated by neuraminidase treatment, suggesting the presence in
      its structure of sialic residue(s). The neuraminidase-sensitive, ESF-like
      activity is readily detected in the medium conditioned with normal mouse bone
      marrow (BM) cells. On fractionation of low MW erythroid products on a reversed
      phase C16 column in a linear acetonitrile gradient (5-95%), ESF activity is
      detected in the first peak alone with the shortest time of its retention by the
      column. The results suggest that (1) by producing ESF, EC may regulate both B-
      and T-cell-mediated immune processes and (2) based on its physicochemical and
      biological characteristics, ESF can be distinguished from each of earlier
      characterised suppressor mediators of bone marrow origin.

PMID- 15158615
TI  - Effect of rLcrV and rYopB from Yersinia pestis on murine peritoneal macrophages
      in vitro.
AB  - The interaction between macrophages and bacterial pathogens is crucial in the
      pathogenesis of infectious diseases. The 70 kb plasmid encodes low calcium
      response V (LcrV) or V antigen and a group of highly conserved yersinia outer
      proteins (Yops) are essential for full virulence. In present study, we
      investigated the effect of rLcrV and rYopB on macrophage functions in vitro. It
      is observed that rLcrV and rYopB inhibited the LPS induced expression of TNF
      alpha, IFN-gamma, KC, IP-10, and IL-12 in macrophages. rLcrV and rYopB caused
      increased expression of IL-10 and TLR2, whereas inhibited TLR4 expression in LPS
      treated macrophages. IL-10 and TLR2 antibodies reversed the rLcrV and rYopB
      induced inhibition of TNF-alpha production by LPS treated macrophages, whereas IL
      4 and TLR4 antibodies had no effect. Our data suggests a possible role of IL-10
      and TLR2 in rLcrV and rYopB mediated inhibition of macrophage function.

PMID- 15158616
TI  - Induction of secretory and tumoricidal activities in peritoneal macrophages
      activated by an acidic heteropolysaccharide (ARAGAL) from the gum of
      Anadenanthera colubrina (Angico branco).
AB  - The immunomodulatory and anti-tumoral effects of an acidic heteropolysaccharide
      containing mainly galactose and arabinose (ARAGAL), isolated from the gum of the
      leguminous tree Anadenanthera colubrina (Angico branco) native to Brazil, were
      studied. It has been demonstrated that activation of mice peritoneal macrophages
      both in vivo and in vitro, increases phagocytic ability and anion superoxide
      production. In order to obtain further insights on the biological effects of
      ARAGAL, the capacity of eliciting peritoneal macrophages and tumor necrosis
      factor-alpha (TNF-alpha) production, and anti-tumoral effect against Sarcoma 180
      (S-180), are now evaluated. Cell eliciting activity was observed in ARAGAL
      treated animals in a dose dependent manner. Treatment of animals with 50, 100 or
      200 mg/kg of ARAGAL increased peritoneal exudate cell (PEC) numbers by
      approximately 18, approximately 44 and approximately 88%, respectively. ARAGAL
      also increased 26-fold TNF-alpha production by peritoneal macrophages.
      Macrophages, treated in vitro for 18 h with ARAGAL, were able to kill Sarcoma 180
      cells, as observed by their structures inside the macrophage cytoplasm. ARAGAL
      (100 mg/kg) showed anti-tumoral activity against S-180 in ascites or solid
      tumors, the tumoral inhibition being 63 and 38%, respectively. The results
      suggest a possible role as a BRM for ARAGAL.

PMID- 15158618
TI  - NK cell depletion diminish tumour-specific B cell responses.
AB  - Natural killer (NK) cells can exercise immediate cytotoxicity against malignant
      cells and thus far modulate the development of tumour directed T cell immunity.
      To investigate the impact of NK cells on the development of tumour directed B
      cell immunity mice were immunised with IMR5-75 human neuroblastoma cells with or
      without prior in vivo NK cell depletion. Flow cytometry analyses gave evidence
      for an impaired IgG response against the cells immunised with. Dissection of Th1
      (IgG2a) and Th2 (IgG1) oriented B cell responses revealed Th1 responses as
      primarily affected, while Th2 oriented B cell responses as measured by flow
      cytometry and GD2 ganglioside-specific ELISA were enforced. The data reveal an
      unexpected impact of NK cells on the development of tumour directed B cell
      responses. Consequently, NK cell function has also to be taken into account when
      developing B cell-based cancer immunotherapy.

PMID- 15158617
TI  - HSP60 and CpG-DNA-oligonucleotides differentially regulate LPS-tolerance of
      hepatic Kupffer cells.
AB  - BACKGROUND/AIMS: Hepatic Kupffer cells (KC) are major regulators of the immune
      response to gut-derived bacterial products; uncontrolled activation of KC by
      bacterial components is of pathogenic relevance in alcoholic hepatitis and septic
      shock. METHODS: We examined the role of bacterial lipopolysaccharide (LPS),
      bacterial and autologous HSP60 and bacterial DNA, which are recognized by innate
      Toll-like receptors, during activation of murine KC. RESULTS: In cultivated KC,
      autologous HSP60 induced a state of LPS-hyporesponsiveness; bacterial DNA did not
      mitigate the response to subsequent LPS-challenge in vitro; in contrast, pre
      treatment of mice with bacterial DNA even significantly increased serum TNF
      levels, liver function tests and mortality in a model of LPS-induced hemorrhagic
      liver failure. CONCLUSION: HSP60 and CpG-DNA differentially modulated the
      threshold of KC activation by LPS and might therefore contribute to the
      regulation of inflammatory immunity to gut-derived bacterial compounds.

PMID- 15158619
TI  - Class I and class II MHC polymorphisms in Mexican patients with Behcet's disease.
AB  - Behcet's disease is a multi-system inflammatory disorder of unknown etiology. The
      disease is more prevalent in Eastern Mediterranean countries and Japan where
      there is a linkage to HLA-B51. Mexican Mestizos are suitable subjects for
      studying the role of ethnicity in the susceptibility to Behcet's disease. High
      resolution HLA class I and class II typing was performed by polymerase chain
      reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot and PCR
      single-strand polymorphism in 32 patients with Behcet's disease and 99 healthy
      ethnically-matched controls. A significant increased frequency of HLA-B(*)44 (P =
      0.02; OR = 2.78; CI 95% = 1.1-7.7), HLA-B(*)52 (P = 0.02; OR = 5.33; CI 95% =
      1.07-29.1), and HLA-B(*)56 (P = 0.003; OR = 4.19; CI 95% = 3.37-5.21) as well as
      HLA-DRB1(*)01 and HLA-DRB1(*)13 (p = 0.007; OR = 3.36; CI 95% = 1.22-9.27) was
      found in Mexican patients with Behcet's disease when compared to controls. The
      low frequency of native markers in Mexican Mestizo patients with Behcet's disease
      suggests that genetic admixture between Eastern Mediterraneans and Orientals with
      Amerindians is a recent event that increased the risk of developing Behcet's
      disease in the Mexican population.

PMID- 15158620
TI  - Blood cell gene expression profiling in rheumatoid arthritis. Discriminative
      genes and effect of rheumatoid factor.
AB  - To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid
      arthritis (RA) and to identify genes differentially expressed in patients and
      healthy individuals, total RNA was isolated from peripheral blood mononuclear
      cells (PBMC) from eight RF-positive and six RF-negative RA patients, and seven
      healthy controls. Gene expression of about 10,000 genes were examined using
      oligonucleotide-based DNA chip microarrays. The analyses showed no significant
      differences in PBMC expression patterns from RF-positive and RF-negative
      patients. However, comparisons of gene expression patterns from all fourteen RA
      patients and healthy controls identified a subset of discriminative genes. These
      results were validated by real time reverse transcription polymerase chain
      reaction (RT-PCR) on another group of RA patients and healthy controls. This
      confirmed that the following genes had a significantly higher expression in RA
      patients than in healthy controls: CD14 antigen, defensin alpha-1 and alpha-3
      (DEFA), fatty-acid-Coenzyme A ligase, long-chain 2 (FACL), ribonuclease 2
      (RNASE2), S100 calcium-binding protein A8 and A12 (S100A8 and S100A12). In
      contrast, the expression of MHC class II, DQ beta1 (HLA-DQB1) was significantly
      reduced in RA patients compared to healthy controls. CONCLUSIONS: With the
      analytical procedure employed, we did not find any indication that RF-positive
      and RF-negative RA are two fundamentally different diseases. Most of the genes
      discriminative between RA patients and healthy individuals are known to be
      involved in immunoinflammatory responses, especially those related to altered
      phagocytic functions.

PMID- 15158622
TI  - OTC statins: a bad decision for public health.

PMID- 15158621
TI  - Peripheral parameters of oxidative stress in patients with infiltrative Graves'
      ophthalmopathy treated with corticosteroids.
AB  - Infiltrative ophthalmopathy, which may develop in patients with Graves' disease,
      is considered an inflammatory disorder of autoimmune background. There is growing
      evidence that changed reactive oxygen species (ROS) metabolism plays an important
      role in pathogenesis of autoimmune diseases. Corticotherapy is a principal method
      of ophthalmopathy treatment, and its therapeutic effect is partially connected
      with influence on ROS generation systems. This study was undertaken to
      investigate corticosteroids treatment influence on blood extracellular indices of
      ROS metabolism in Graves' ophthalmopathy patients. Plasma indices of free radical
      generation and scavenging were determined in 22 euthyroid patients with active
      infiltrative Graves' ophthalmopathy initially, after intensive corticotherapy and
      after completing of steroid treatment. Age- and sex-matched 24 healthy volunteers
      and 25 euthyroid Graves' patients without overt ophthalmopathy served as
      controls. In the ophthalmopathy patients hydrogen peroxide (H(2)O(2)), lipid
      hydroperoxides (ROOH), thiobarbituric acid-reacting substances (TBARS) and
      ceruloplasmin (CP) levels and superoxide dismutase (SOD) and catalase (CAT)
      activities were increased, whereas glutathione peroxidase (GPx) and glutathione
      reductase (GR) activities were reduced. Intensive corticotherapy resulted in
      normalization (partial for ROOH) of ROS metabolism peripheral markers. After the
      withdrawal of corticosteroids a reduction of ophthalmopathy clinical activity was
      present, yet a marked restoration of increased oxidative stress indices was
      observed, along with activation of antioxidant defence systems (not significant
      for CAT activity). These data demonstrate that corticosteroids are effective in
      reduction of peripheral oxidative stress present in infiltrative Graves'
      ophthalmopathy, but this effect tends to be transient.

PMID- 15158623
TI  - Beyond randomised versus observational studies.

PMID- 15158624
TI  - In-vitro model offers insight into the pathophysiology of severe malaria.

PMID- 15158625
TI  - Tongue transplantation.

PMID- 15158626
TI  - Rape of individuals with disability: AIDS and the folk belief of virgin
      cleansing.

PMID- 15158627
TI  - Whole brain radiation therapy with or without stereotactic radiosurgery boost for
      patients with one to three brain metastases: phase III results of the RTOG 9508
      randomised trial.
AB  - BACKGROUND: Brain metastases occur in up to 40% of all patients with systemic
      cancer. We aimed to assess whether stereotactic radiosurgery provided any
      therapeutic benefit in a randomised multi-institutional trial directed by the
      Radiation Therapy Oncology Group (RTOG). METHODS: Patients with one to three
      newly diagnosed brain metastases were randomly allocated either whole brain
      radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost.
      Patients were stratified by number of metastases and status of extracranial
      disease. Primary outcome was survival; secondary outcomes were tumour response
      and local rates, overall intracranial recurrence rates, cause of death, and
      performance measurements. FINDINGS: From January, 1996, to June, 2001, we
      enrolled 333 patients from 55 participating RTOG institutions--167 were assigned
      WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate
      analysis showed that there was a survival advantage in the WBRT and stereotactic
      radiosurgery group for patients with a single brain metastasis (median survival
      time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group
      were more likely to have a stable or improved Karnofsky Performance Status (KPS)
      score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%,
      respectively; p=0.03). By multivariate analysis, survival improved in patients
      with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).
      INTERPRETATION: WBRT and stereotactic boost treatment improved functional
      autonomy (KPS) for all patients and survival for patients with a single
      unresectable brain metastasis. WBRT and stereotactic radiosurgery should,
      therefore, be standard treatment for patients with a single unresectable brain
      metastasis and considered for patients with two or three brain metastases.

PMID- 15158628
TI  - Effects of morphine analgesia in ventilated preterm neonates: primary outcomes
      from the NEOPAIN randomised trial.
AB  - BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We
      undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN)
      trial to investigate whether pre-emptive morphine analgesia decreases the rate of
      a composite primary outcome of neonatal death, severe intraventricular
      haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates.
      METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly
      assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading
      dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(
      1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1))
      were continued as long as clinically justified (maximum 14 days). Open-label
      morphine could be given on clinical judgment (placebo group 242/443 [54.6%],
      morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS:
      Baseline variables were similar in the randomised groups. The placebo and
      morphine groups had similar rates of the composite outcome (105/408 [26%] vs
      115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429
      [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who
      were not given open-label morphine, rates of the composite outcome (53/225 [24%]
      vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209)
      were higher in the morphine group than the placebo group. Placebo-group neonates
      receiving open-label morphine had worse rates of the composite outcome than those
      not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001).
      Morphine-group neonates receiving open-label morphine were more likely to develop
      severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION: Pre-emptive
      morphine infusions did not reduce the frequency of severe IVH, PVL, or death in
      ventilated preterm neonates, but intermittent boluses of open-label morphine were
      associated with an increased rate of the composite outcome. The morphine doses
      used in this study decrease clinical signs of pain but can cause significant
      adverse effects in ventilated preterm neonates.

PMID- 15158629
TI  - Zinc for severe pneumonia in very young children: double-blind placebo-controlled
      trial.
AB  - BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in young
      children. Early reversal of severity signs--chest indrawing, hypoxia, and
      tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant,
      would shorten duration of severe pneumonia and time in hospital. METHODS: In a
      double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh,
      270 children aged 2-23 months were randomised to receive elemental zinc (20 mg
      per day) or placebo, plus the hospital's standard antimicrobial management, until
      discharge. The outcomes were time to cessation of severe pneumonia (no chest
      indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on
      room air) and discharge from hospital. Discharge was allowed when respiratory
      rate was 40 per minute or less for 24 consecutive hours while patients were
      maintained only on oral antibiotics. FINDINGS: The group receiving zinc had
      reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51
      0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate
      more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and
      overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to
      1 hospital day for both severe pneumonia and time in hospital. All effects were
      greater when children with wheezing were omitted from the analysis.
      INTERPRETATION: Adjuvant treatment with 20 mg zinc per day accelerates recovery
      from severe pneumonia in children, and could help reduce antimicrobial resistance
      by decreasing multiple antibiotic exposures, and lessen complications and deaths
      where second line drugs are unavailable.

PMID- 15158630
TI  - Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the
      nasal mucosa of atopic children but not adults.
AB  - BACKGROUND: Exposure to bacterial products in early life could protect against
      development of atopy. We examined the effect of bacterial lipopolysaccharide on
      allergic inflammation and expression of cytokines and lipopolysaccharide receptor
      (toll-like receptor 4 TLR4) in nasal mucosa of 15 atopic children and ten atopic
      adults. METHODS: Explanted mucosa was cultured with allergen with or without
      lipopolysaccharide (0.1 mg/L) for 24 h. Immunocytochemistry and in-situ
      hybridisation were used to phenotype the cells and cytokines. FINDINGS: In
      explants from atopic children, lipopolysaccharide prevented allergen-induced T
      helper type 2 (Th2) inflammation and upregulated Th1 cytokine reactivity and
      expression. These effects were blocked by antibody to interleukin 10. In children
      but not in adults, lipopolysaccharide caused increases of three times in T-cell
      reactivity, five times in T-cell proliferation, and four times in expression of
      interleukin 10 compared with mucosa stimulated with allergen alone. This
      difference in response was mirrored by lipopolysaccharide-induced increases in
      TLR4 reactivity in children but not adults. TLR4 receptor was expressed by CD3
      positive T cells, and TLR4-positive cells contained interleukin 10.
      Lipopolysaccharide increased expression of cells positive for both CD3 and TLR4;
      both TLR4 and interleukin 10; and both CD4 and CD25. INTERPRETATION:
      Lipopolysaccharide inhibits allergic inflammation in nasal mucosa of atopic
      children by skewing local immune responses from Th2 to Th1 and upregulating
      production of interleukin 10. These effects are mediated by TLR4. Our results
      emphasise an important difference between adults and children in their ability to
      respond to bacterial products. These differences could have a role in normal
      maturation of the immune system.

PMID- 15158631
TI  - Recurrent acroparaesthesia during febrile infections.

PMID- 15158632
TI  - Viral shedding patterns of coronavirus in patients with probable severe acute
      respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is thought to be caused by a novel
      coronavirus, SARS-associated coronavirus. We studied viral shedding of SARS
      coronavirus to improve diagnosis and infection control. Reverse-transcriptase PCR
      was done on 2134 specimens of different types. 355 (45%) specimens of
      nasopharyngeal aspirates and 150 (28%) of faeces were positive for SARS
      coronavirus RNA. Positive rates peaked at 6-11 days after onset of illness for
      nasopharyngeal aspirates (87 of 149 [58%], to 37 of 62 [60%]), and 9-14 days for
      faeces (15 of 22 [68%], to 26 of 37 [70%]). Overall, peak viral loads were
      reached at 12-14 days of illness when patients were probably in hospital care,
      which would explain why hospital workers were prone to infection. Low rate of
      viral shedding in the first few days of illness meant that early isolation
      measures would probably be effective.

PMID- 15158633
TI  - Genomic imprinting in disruptive spermatogenesis.
AB  - The possibility of imprinting disease transmission by assisted reproductive
      technologies has been raised after births of children with Angelman's and
      Beckwith-Wiedemann's syndromes. To investigate whether imprinting defects were
      associated with disturbed spermatogenesis, we studied two oppositely imprinted
      genes in spermatozoan DNA from normozoospermic and oligozoospermic patients. In
      the mesodermal specific transcript gene (MEST), bisulphite genomic sequencing
      showed that maternal imprinting was correctly erased in all 123 patients.
      However, methylation of the H19 gene did not change in any of 27 normozoospermic
      individuals (0%, 95% CI 0-13%), compared with methylation changes in eight
      moderate (17%, 8-31%, p=0.026) and 15 severe (30%, 18-45%, p=0.002)
      oligozoospermic patients. Our data suggest an association between abnormal
      genomic imprinting and hypospermatogenesis, and that spermatozoa from
      oligozoospermic patients carry a raised risk of transmitting imprinting errors.

PMID- 15158634
TI  - Primary open-angle glaucoma.
AB  - Primary open-angle glaucoma is a progressive optic neuropathy and, perhaps, the
      most common form of glaucoma. Because the disease is treatable, and because the
      visual impairment caused by glaucoma is irreversible, early detection is
      essential. Early diagnosis depends on examination of the optic disc, retinal
      nerve fibre layer, and visual field. New imaging and psychophysical tests can
      improve both detection and monitoring of the progression of the disease. Recently
      completed long-term clinical trials provide convincing evidence that lowering
      intraocular pressure prevents progression at both the early and late stages of
      the disease. The degree of protection is related to the degree to which
      intraocular pressure is lowered. Improvements in therapy consist of more
      effective and better-tolerated drugs to lower intraocular pressure, and more
      effective surgical procedures. New treatments to directly treat and protect the
      retinal ganglion cells that are damaged in glaucoma are also in development.

PMID- 15158636
TI  - Drug intervention trials in sepsis: divergent results.
AB  - CONTEXT: Important advances have been made in our understanding of severe sepsis.
      Outcome can be improved by targeted interventions, including early and
      appropriate antibiotic therapy and goal-directed resuscitation, and might be
      further improved by selective decontamination of the digestive tract, tight
      control of glucose, and possibly by giving corticosteroids to selected patients.
      Drugs that target specific steps in the septic cascade include cytokine
      inhibitors, anti-endotoxins, and the three naturally occurring anticoagulants.
      Only one of these trials, which assessed the efficacy of activated protein C,
      reported significant improvements in outcome. Translation of these results into
      practice has been hampered by high drug costs, and by apparent discrepancies
      between interim results and final outcomes in two of the trials with natural
      anticoagulants. STARTING POINT: Recently, Steven Opal and colleagues (Crit Care
      Med 2004; 32: 332-41) reported a randomised trial with platelet-activating-factor
      acetylhydrolase to suppress the inflammatory response in septic patients. No
      effects on outcome were observed (mortality 24% with placebo vs 25% with the
      intervention). By contrast, Jose Garnacho-Montero and colleagues, in a cohort
      study (Crit Care Med 2003; 31: 2742-51), saw large mortality reductions with
      initially appropriate choice of antibiotics in septic patients (19.8% reduction
      overall and 43.4% in patients with septic shock). These benefits were higher than
      those even in the most successful trial with an antisepsis agents, underscoring
      the importance of basic measures in severe sepsis. WHERE NEXT? Initial management
      in severe sepsis should include early goal-directed fluid resuscitation,
      appropriate antibiotic treatment, and surgical-site control. Intensive-care units
      should be run by specialists, with adequate medical and nursing staffing. Tight
      regulation of glucose, selective decontamination of the digestive tract, and
      moderate-dose corticosteroids in selected cases should be considered. Expensive
      new drugs, such as activated protein C, might further improve outcome, but should
      be considered only when organisational aspects and supportive care have been
      optimised.

PMID- 15158637
TI  - Those confounded vitamins: what can we learn from the differences between
      observational versus randomised trial evidence?

PMID- 15158638
TI  - When are observational studies as credible as randomised trials?

PMID- 15158639
TI  - Depressing misrepresentation?

PMID- 15158640
TI  - Depressing misrepresentation?

PMID- 15158641
TI  - Etanercept and methotrexate in rheumatoid arthritis.

PMID- 15158643
TI  - African women, bride price, and AIDS.

PMID- 15158644
TI  - Etanercept and methotrexate in rheumatoid arthritis.

PMID- 15158645
TI  - Stem-cell therapy for myocardial diseases.

PMID- 15158647
TI  - Stem-cell therapy for myocardial diseases.

PMID- 15158648
TI  - Preventive oncology.

PMID- 15158649
TI  - Trachoma still ignored in developing countries.

PMID- 15158650
TI  - Preventive oncology.

PMID- 15158651
TI  - Traditional Japanese dietary basics: a solution for modern health issues?

PMID- 15158652
TI  - Selective quotation of evidence in vaccines research.

PMID- 15158653
TI  - Moacyr Scliar.

PMID- 15158655
TI  - Eugenics.

PMID- 15158656
TI  - Kieran Sweeney.

PMID- 15158658
TI  - Victor Ginsburg (1930-2003): an unforgettable lab chief and mentor and a founder
      of glycobiology.

PMID- 15158661
TI  - The third chains of living organisms--a trail of glycobiology that started from
      the third floor of building 4 in NIH.
AB  - Application of a finger-printing method to the analysis of human milk
      oligosaccharides led to the finding that several oligosaccharides were missing in
      the milk of non-secretor or Lewis-negative individuals. This finding helped us in
      opening the door of elucidating the enzymatic basis of blood types in human.
      Based on these successful studies, a strategy to establish reliable techniques to
      elucidate the structures and functions of the N-linked sugar chains of
      glycoproteins was devised. It was to contrive enzymatic and chemical means to
      release quantitatively the N-linked sugar chains as oligosaccharides, and finger
      print them by using appropriate methods to demonstrate the sugar pattern of a
      glycoprotein. These methods enabled us to determine that the N-linked sugar
      chains of glycoproteins can be classified into three subgroups: high mannose
      type, complex-type, and hybrid-type. By comparative studies of the sugar patterns
      of a glycoprotein produced by different organs and different animals, occurrences
      of organ- and species-specific glycosylation were found in many glycoproteins. By
      comparative studies of the glycosylation patterns of the subunits constructing
      human chorionic gonadotropin and other glycoproteins, occurrence of site-directed
      N-glycosylation was also found, indicating that the processing and maturation of
      the N-linked sugar chains of a glycoprotein might be controlled by the structure
      of polypeptide moiety. Furthermore, these methods enabled us to elucidate the
      structural alteration of the sugar chains of a glycoprotein induced by diseased
      state of the producing cells, such as rheumatoid arthritis and malignancy. Recent
      studies of glycoproteins in the brain-nervous system through aging revealed that
      N-glycosylation of P(0) in the rat spinal cord is induced by aging. Therefore,
      glycobiology is expanding tremendously into fields such as pathological and
      gerontological research.

PMID- 15158662
TI  - The discovery, biology, and drug development of sialyl Lea and sialyl Lex.
AB  - The discoveries of sialylated, fucosylated lacto-, and neolacto-type carbohydrate
      structures were accomplished with the aid of analytical methods and monoclonal
      antibodies such as the immunostaining of thin layer chromatograms. Based on the
      use of such antibodies, these structures, notably sialyl Le(a) and sialyl Le(x),
      were demonstrated to be highly expressed in many malignant cancers. A diagnostic
      assay using one of these antibodies (CA19-9) is now established as one of the
      more commonly used assays for pancreatic and gastrointestinal cancers worldwide.
      Upon further study, several laboratories have demonstrated that the level of
      expression of these carbohydrate tumor markers is also positively correlated with
      patient survival and is a prognostic indicator of metastatic disease. Concurrent
      with this finding, both sialyl Le(a) and sialyl Le(x) were shown to bind to a
      family of carbohydrate-binding proteins involved in the extravasation of cells
      from the bloodstream, called the selectins. Thus, sialyl Le(a) and sialyl Le(x)
      expressed on cell surfaces play functional roles in medical conditions that
      require extravasation of cells from the bloodstream which include a wide range of
      inflammatory diseases and cancer metastasis. Many studies have confirmed the
      function of sialyl Le(a) and sialyl Le(x) in animal models of these diseases and
      the inhibition of binding of sialyl Le(a) and sialyl Le(x) to the selectins is a
      validated drug target in the pharmaceutical industry. Thus, a new class of drugs,
      arising from the field of glycobiology, is based on the rational design of small
      molecule drugs that mimic the structures sialyl Le(a) and sialyl Le(x) and can
      potently inhibit their functional binding to the selectins.

PMID- 15158663
TI  - Victor Ginsburg's influence on my research of the role of sialic acids in
      biological recognition.
AB  - Sialic acids are monosaccharides with relatively strong acidity which belong to
      the most important molecules of higher animals and also occur in some
      microorganisms. They are bound to complex carbohydrates and occupy prominent
      positions, especially in cell membranes. Their structural diversity is high and,
      correspondingly, the mechanisms for their biosynthesis complex. Sialic acids are
      involved in a great number of cell functions. Due to their cell surface location
      these acidic molecules shield macromolecules and cells from enzymatic and
      immunological attacks and thus contribute to innate immunity. In contrast to this
      masking role, enabling, for example, blood cells and serum glycoproteins a longer
      life-time, sialic acids also represent recognition sites for various
      physiological receptors, such as the selectins and siglecs, as well as for toxins
      and microorganisms and thus allow their colonization. The recognition function of
      sialic acids can again be masked by O-acetylation, which modifies the interaction
      with receptors. Many viruses use sialic acids for the infection of cells. As
      sialic acids play also a decisive role in tumor biology, they prove to be rather
      versatile molecules that modulate biological and pathological cellular events in
      a sensitive way. Thus, they are most prominent representatives of mediators of
      molecular and cellular recognition.

PMID- 15158664
TI  - Polyagglutination NOR: new glycosphingolipid antigens recognized by a new type of
      common human anti-alpha-galactosyl antibodies.

PMID- 15158665
TI  - Sensing the host environment: recognition of hemoglobin by the pathogenic yeast
      Candida albicans.
AB  - Adhesion to host cells and tissues is important for several steps in the
      pathogenesis of disseminated Candida albicans infections. Although such adhesion
      is evident in vivo and for C. albicans grown in vitro in complex medium, some
      adhesive activities are absent when cultures are grown in defined media. However,
      addition of hemoglobin to defined media restores binding and adhesion to several
      host proteins. This activity of hemoglobin is independent of iron acquisition and
      is mediated by a cell surface hemoglobin receptor. In addition to regulating
      expression of adhesion receptors, hemoglobin rapidly induces expression of
      several genes. One of these, a heme oxygenase, allows the pathogen to utilize
      exogenous heme or hemoglobin to acquire iron and to produce the cytoprotective
      molecules alpha-biliverdin and carbon monoxide. The specific recognition of and
      responses to hemoglobin demonstrate a unique adaptation of C. albicans to be both
      a commensal and an opportunistic pathogen in humans.

PMID- 15158666
TI  - The role of sulfatide in thrombogenesis and haemostasis.
AB  - In 1961, Wago et al. reported a potential anticoagulant role for sulfatide using
      animal experiments. Since then there have been many studies of sulfatide in the
      field of thrombogenesis/haemostasis, yielding contradictory conclusions. Some
      report that sulfatide has anti-thrombotic activity because it prolongs clotting
      time, inhibits platelet adhesion, and prolongs bleeding. Others report that
      sulfatide induces thrombosis in animal models. This mini-review is a chronologic
      review of reports examining the role of sulfatide in thrombogenesis/haemostasis
      together with the introduction of data from our laboratory and a discussion of
      the possible mechanisms underlying these curious phenomena.

PMID- 15158667
TI  - Glycolipid-mediated cell-cell recognition in inflammation and nerve regeneration.
AB  - Cell surface complex carbohydrates have emerged as key recognition molecules,
      mediating physiological interactions between cells. Typically, glycans on one
      cell surface are engaged by complementary carbohydrate binding proteins (lectins)
      on an apposing cell, initiating appropriate cellular responses. Although many
      cell surface lectins have been identified in vertebrates, only a few of their
      endogenous carbohydrate ligands have been established. Each major class of cell
      surface glycans-glycoproteins, glycolipids, and proteoglycans-has been implicated
      as physiologically relevant lectin ligands. The current minireview focuses on
      findings that implicate glycosphingolipids as especially important molecules in
      cell-cell recognition in two different systems: the recognition of human
      leukocytes by E-selectin on the vascular endothelium during inflammation and the
      recognition of nerve cell axons by myelin-associated glycoprotein in myelin-axon
      stabilization and the regulation of axon regeneration.

PMID- 15158668
TI  - Carbohydrate-to-carbohydrate interaction in basic cell biology: a brief overview.

PMID- 15158670
TI  - The septation apparatus, a chitin-requiring machine in budding yeast.

PMID- 15158669
TI  - Antigenic glycans in parasitic infections: implications for vaccines and
      diagnostics.
AB  - Infections by parasitic protozoans and helminths are a major world-wide health
      concern, but no vaccines exist to the major human parasitic diseases, such as
      malaria, African trypanosomiasis, amebiasis, leishmaniasis, schistosomiasis, and
      lymphatic filariasis. Recent studies on a number of parasites indicate that
      immune responses to parasites in infected animals and humans are directed to
      glycan determinants within cell surface and secreted glycoconjugates and that
      glycoconjugates are important in host-parasite interactions. Because of the
      tremendous success achieved recently in generating carbohydrate-protein conjugate
      vaccines toward microbial infections, such as Haemophilus influenzae type b,
      there is renewed interest in defining parasite-derived glycans in the prospect of
      developing conjugate vaccines and new diagnostics for parasitic infections.
      Parasite-derived glycans are compelling vaccine targets because they have
      structural features that distinguish them from mammalian glycans. There have been
      exciting new developments in techniques for glycan analysis and the methods for
      synthesizing oligosaccharides by chemical or combined chemo-enzymatic approaches
      that now make it feasible to generate parasite glycans to test as vaccine
      candidates. Here, we highlight recent progress made in elucidating the
      immunogenicity of glycans from some of the major human and animal parasites, the
      potential for developing conjugate vaccines for parasitic infections, and the
      possible utilization of these novel glycans in diagnostics.

PMID- 15158671
TI  - Lipid rafts-protein association and the regulation of protein activity.
AB  - Lipid rafts are membrane microdomains enriched in saturated phospholipids,
      sphingolipids, and cholesterol. They have a varied but distinct protein
      composition and have been implicated in diverse cellular processes including
      polarized traffic, signal transduction, endo- and exo-cytoses, entrance of
      obligate intracellular pathogens, and generation of pathological forms of
      proteins associated with Alzheimer's and prion diseases. Raft proteins can be
      permanently or temporarily associated to lipid rafts. Here, we review recent
      advances on the biochemical and cell biological characterization of rafts, and on
      the emerging concept of the temporary residency of proteins in rafts as a
      regulatory mechanism of their biological activity.

PMID- 15158672
TI  - The cytoplasmic tail of the cation-independent mannose 6-phosphate receptor
      contains four binding sites for AP-1.
AB  - The trafficking of the cation-independent mannose 6-phosphate receptor between
      the trans-Golgi network and endosomes requires binding of sorting determinants in
      the cytoplasmic tail of the receptor to adaptor protein complex-1 (AP-1). Using a
      GST pull-down binding assay, four binding motifs were identified in the
      cytoplasmic tail: a tyrosine-based motif ((26)YSKV(29)), an internal dileucine
      based motif ((39)ETEWLM(44)), and two casein kinase 2 sites ((84)DSEDE(88) and
      (154)DDSDED(159)). The YSKV motif mediated the strongest interaction with AP-1
      and the two CK2 motifs bound AP-1 only when they were phosphorylated. The COOH
      terminal dileucines were not required for interaction with AP-1.

PMID- 15158673
TI  - Functional characterization of a novel Toxoplasma gondii glycosyltransferase: UDP
      N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3.
AB  - We report the functional characterization of a new UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase (ppGalNAc-T) (EC 2.4.1.41) from the human disease
      causing parasite, Toxoplasma gondii. This glycosyltransferase is denoted as T.
      gondii ppGalNAc-T3. These enzymes are responsible for the initial step of mucin
      type O-glycosylation: the transfer of GalNAc from the UDP-GalNAc nucleotide sugar
      donor onto a peptide acceptor. Following an in silico analysis of the publicly
      available T. gondii DNA database, we used molecular biology approaches to
      identify and isolate the cDNA encoding this enzyme. The resulting type II
      membrane protein contains N-terminal cytoplasmic, transmembrane, and C-terminal
      lumenal domains. Conceptual translation of the cDNA sequence also reveals a stem
      region and the presence of several important sequence motifs. When the
      recombinant construct was expressed in stably transfected Drosophila melanogaster
      S2 cells, the purified protein exhibited glycosyltransferase activity in vitro
      against glycopeptide, but not "naked" peptide, acceptors. In addition, using
      reverse transcriptase-PCR, T. gondii ppGalNAc-T3 mRNA was equivalently expressed
      during the tachyzoite and bradyzoite developmental stages. The identification of
      T. gondii ppGalNAc-T3 as a functional "follow-up" glycopeptide
      glycosyltransferase further confirms that this human parasite has its own
      enzymatic O-glycosylation machinery.

PMID- 15158674
TI  - Probing genetic variation and glycoform distribution in lectins of the Erythrina
      genus by mass spectrometry.
AB  - Six leguminous lectins from the seeds of plants of the Erythrina genus, namely E.
      caffra (ECafL), E. cristagalli (ECL), E. flabelliformis (EFL), E. lysistemon
      (ELysL), E. rubrinerva (ERL), and E. vespertilio (EVL), were examined to
      establish their sequence homology and to determine the structure and sites of
      attachment of their glycans. Tryptic digests of these lectins were analyzed by
      capillary electrophoresis coupled to electrospray mass spectrometry (CE-ESMS).
      Assignments were made by comparing the molecular masses of the observed tryptic
      peptides with those of Erythrina corallodendron lectin (ECorL), the sequence of
      which had been established previously. Glycan structure and genetic variations in
      the amino acid sequence were probed by tandem mass spectrometry. Small
      differences were found between the sequences of the various lectins examined and
      all of them exhibited C-terminal processing resulting in proteins with a C
      terminal Asn residue. The major glycan of these glycoproteins was shown to be the
      heptasaccharide Man(3)XylFucGlcNAc(2), consistent with previous investigations on
      ECL and ECorL. A minor glycan heterogeneity was observed for most lectins
      examined except for that of ECafL and ECorL where an extra hexose residue was
      observed on the reducing GlcNAc residue of the heptasaccharide.

PMID- 15158676
TI  - Polylactosamine synthesis and branch formation of N-glycans in beta1,4
      galactosyltransferase-1-deficient mice.
AB  - Analysis of glycans from erythrocyte membrane glycoproteins from beta1,4
      galactosyltransferase-1 (beta4GalT-1)-deficient mice revealed moderately
      decreased galactosylation but comparable polylactosamine content compared to
      control beta4GalT-1(+/-) mice. The increased expression of more branched N
      glycans was observed in beta4GalT-1(-/-) mice, and its extent was more remarkable
      in elder beta4GalT-1(-/-) mice (28 weeks old) than in younger beta4GalT-1(-/-)
      mice (6-9 weeks old). In relation to this issue, the less galactosylation of
      biantennary glycans was observed in the elder group, suggesting that beta4GalTs
      actually compete with N-acetylglucosaminyltransferases IV and V in erythroid
      cells. In contrast, approximately 80% of core 2 O-glycans were not beta1,4
      galactosylated regardless of age of the knockout mice. These results suggest that
      beta4GalT-1 expressed in erythroid cells may regulate a constant branch formation
      of N-glycans and plays a predominant role in beta1,4-galactosylation of core 2 O
      glycan.

PMID- 15158675
TI  - Cloning and expression of the trehalose-phosphate phosphatase of Mycobacterium
      tuberculosis: comparison to the enzyme from Mycobacterium smegmatis.
AB  - Two open reading frames in the Mycobacterium tuberculosis genome, Rv3372 and
      Rv2006, have about 25% sequence identity at the amino acid level to the trehalose
      phosphate phosphatase (TPP) purified from Mycobacterium smegmatis. However, the
      protein produced from the cloned Rv3372 gene has a molecular weight of about
      45kDa whereas the trehalose-P phosphatase purified from M. smegmatis has a
      molecular weight of about 27kDa. We expressed the Rv3372 protein in Escherichia
      coli and show here that it is a trehalose-P phosphatase with very similar
      properties to the M. smegmatis TPP, i.e., complete specificity for trehalose
      phosphate as the substrate, an almost absolute requirement for Mg(2+), and a pH
      optimum of 7-7.5. On the other hand, in contrast to the M. smegmatis enzyme, the
      Rv3372 protein was much less stable to heat and much less sensitive to inhibition
      by diumycin and moenomycin. In fact, both of these antibiotics stimulate enzyme
      activity at low concentrations and only inhibit the activity at higher antibiotic
      concentrations. Antibody prepared against the 27kDa TPP does not cross react with
      the 45kDa TPP nor does antibody against the 45kDa TPP cross react with the 27kDa
      TPP. Nevertheless, studies of secondary structure by circular dichroism indicate
      that the two enzymes are quite similar in structure. The product of the other
      gene, Rv2006, is a 159kDa protein with no detectable phosphatase activity. Thus,
      its function is currently unknown.

PMID- 15158677
TI  - Controlled glycosylation of therapeutic antibodies in plants.
AB  - Recombinant therapeutic monoclonal antibodies (mAb) can be expressed, assembled,
      and glycosylated in plants. Transgenic plants, producing anti-rabies mAb and anti
      colorectal cancer mAb, were obtained from Agrobacterium-mediated transformation.
      The heavy chain (HC) of anti-rabies mAb was fused to the Lys-Asp-Glu-Leu (KDEL)
      endoplasmic reticulum retention signal whereas the HC of anti-colorectal cancer
      mAb was not fused to the KDEL sequence. Gel release of glycans and detection by
      high-performance liquid chromatography (HPLC), together with computer assisted
      analysis and matrix-assisted laser desorption/ionization time-of-flight (MALD
      TOF) mass spectrometry, revealed that the plant-derived anti-rabies mAb with KDEL
      contained mainly oligomannose type N-glycans while the plant-derived anti
      colorectal cancer mAb carried mainly biantennary glycans with and without a
      pentose sugar, that is thought to be xylose. This finding indicates that the KDEL
      sequence can affect the N-glycosylation processing of antibody in plant cells.
      The plant-derived mAbs with addition of a KDEL sequence did not contain any of
      the known antigenic glycan epitopes that are frequently found in other plant
      glycans or in mammalian-derived mAbs. The altered glycosylation on both plant
      derived mAbs did not affect the activities that are required for therapy. These
      results indicate that plant genetic engineering could provide an effective and
      inexpensive means to control the glycosylation of therapeutic proteins such as
      mAbs, by the addition of a KDEL signal as a regulatory element.

PMID- 15158678
TI  - Galactosylceramide expression factor-1 induces myogenesis in MDCK and C3H10T1/2
      cells.
AB  - We previously reported that galactosylceramide expression factor-1 (GEF-1), a rat
      homolog of hepatocyte growth factor-regulated tyrosine kinase substrate
      (Hrs/Hgs), induces galactosylceramide and/or sulfatide expression and
      morphological changes in epithelial cells. Here, we show that GEF-1 induces
      myogenesis in MDCK and C3H10T1/2 cells. GEF-1 overexpression in MDCK cells
      (MDCK/GEF-1) appeared to promote trans-differentiation to myoblasts that
      expressed MyoD and myosin heavy chain (MHC). MDCK/GEF-1 cells also expressed
      several DNA-binding proteins (MyoD and MEF-2) that are essential for myogenesis.
      These results suggest that GEF-1 induces MDCK cells to enter an early stage of
      myogenesis. Subsequently, we tested whether GEF-1 could induce myogenesis in
      C3H10T1/2 mouse fibroblasts, which have the potential to differentiate into
      myoblast-like cells. Indeed, GEF-1 induced morphological changes that were
      consistent with myoblast-like cells, and both MyoD and MHC were expressed. Our
      results suggest that GEF-1 may induce MDCK and C3H10T1/2 cells to trans
      differentiate into myoblast-like cells.

PMID- 15158679
TI  - Mutation of active site residues in the chitin-binding domain ChBDChiA1 from
      chitinase A1 of Bacillus circulans alters substrate specificity: use of a green
      fluorescent protein binding assay.
AB  - A fluorescent binding assay was developed to investigate the effects of
      mutagenesis on the binding affinity and substrate specificity of the chitin
      binding domain of chitinase A1 from Bacillus circulans WL-12. The chitin-binding
      domain was genetically fused to the N-terminus of a green fluorescent protein,
      and the polyhistidine-tagged hybrid protein was expressed in Escherichia coli.
      Residues likely to be involved in the binding site were mutated and their
      contributions to binding and substrate specificity were evaluated by affinity
      electrophoresis and depletion assays. The experimental binding isotherms were
      analyzed by non-linear regression using a modified Langmuir equation. Non
      conservative substitution of tryptophan residue (W687) nearly abolished chitin
      binding affinity and dramatically lowered chitosan binding while retaining the
      original level of curdlan binding. Double mutation E668K/P689A had altered
      specificity for several substrates and also impaired chitin binding
      significantly. Other substitutions in the binding site altered substrate
      specificity but had little effect on overall affinity for chitin. Interestingly,
      mutation T682A led to a higher specificity towards chitinous substrates than the
      wildtype. Furthermore, the ChBD-GFP hybrid protein was tested for use in
      diagnostic staining of cell walls of fungi and yeast and for the detection of
      fungal infections in tissue samples.

PMID- 15158680
TI  - Recognition by TNF-alpha of the GPI-anchor glycan induces apoptosis of U937
      cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) binds to TNF-alpha receptors (TNFR) to
      produce a hexameric (TNF-alpha)(3)-(TNFR)(3) structure that stimulates apoptosis.
      We found by using ELISA that TNF-alpha binds to the glycosylphosphatidylinositol
      (GPI) anchor glycans of carcinoembryonic antigen, human placental alkaline
      phosphatase (hAP), and Tamm-Horsfall glycoprotein. These binding abilities were
      inhibited by 10(-6)M mannose-6-phosphate. Treatment of hAP with mild acid and
      phosphatase, which releases the N-acetylglucosamine (GlcNAc) beta1 -->phosphate-
      >6 residue from the GPI-anchor glycan of hAP, abrogated the binding of TNF-alpha
      to hAP. Thus, TNF-alpha binds to the GlcNAcbeta1-->phosphate-->6Man residue in
      GPI-anchor glycans. To investigate whether the carbohydrate-binding ability of
      TNF-alpha is related to its physiological functions, human lymphoma U937 cells
      were used. TNF-alpha stimulates U937 cell apoptosis in a dose-dependent manner
      and the presence of mannose-6-phosphate inhibited this. TNF-alpha-dependent
      tyrosine phosphorylation of several proteins in U937 cells was also diminished by
      mannose-6-phosphate. Phosphatidylinositol-specific phospholipase C-pretreatment
      also inhibited this tyrosine phosphorylation. These data suggest that TNF-alpha
      stimulates U937 cell apoptosis by forming a high-affinity nanomeric (TNF
      alpha)(3)-(TNFR)(3)-(GPI-anchored glycan)(3) complex. The GPI-anchored
      glycoprotein involved remains to be identified.

PMID- 15158682
TI  - Challenges to prevent dengue among German travelers to endemic areas.

PMID- 15158681
TI  - Rapid cell senescence-associated changes in galactosylation of N-linked
      oligosaccharides in human lung adenocarcinoma A549 cells.
AB  - Rapid senescence was induced into human lung adenocarcinoma A549 cells by
      transforming growth factor-beta1. Lectin blot analysis of membrane glycoprotein
      samples showed that the binding of Ricinus communis agglutinin-I to protein bands
      increased markedly while those of other lectins together with protein components
      did not change significantly with senescence. This indicates that the beta-1,4
      galactosylation of N-linked oligosaccharides is stimulated by rapid senescence.
      Analysis of the enzymatic background of senescence showed 1.5 times higher beta
      1,4-galactosyltransferase (beta-1,4-GalT) activity and 2-5 times higher
      expression levels of beta-1,4-GalT II, III, V, and VI genes are associated with
      rapid senescence. Incubation of the cells on RCA-I-coated plates in the absence
      of fetal calf serum showed that the viability of the senescent cells is half that
      of the control cells. Therefore, it is hypothesized that galactose residues
      expressed by rapid senescent can induce a lethal signal in cells if they interact
      with appropriate receptors.

PMID- 15158684
TI  - Ultrasonographic diagnosis and medical treatment of human cystic echinococcosis
      in asymptomatic school age carriers: 5 years of follow-up.
AB  - Hydatidosis or cystic echinococcosis (CE) caused by Echinococcus granulosus is
      endemic in the Province of Rio Negro, Argentina. The objective of this
      investigation was to evaluate the results of a program carried out in endemic
      areas of the Province of Rio Negro, Argentina, in the years 1997-2002. Abdominal
      ultrasonography was used, classifying the cases detected according to WHO
      guidelines. A treatment algorithm was defined which included observation,
      albendazol therapy, PAIR or surgery, according to cyst type and size. A total of
      5745 schoolchildren were evaluated, detecting hydatid cyst carriers in 70 (1.2%).
      Of these; 40 (57.1%) were included in follow-up protocol, 25 (35.7%) in treatment
      protocol with albendazol, 2 (2.9%) with PAIR and 3 (4.3%) with conventional
      surgery. After a mean of 44 months, among 25 cases treated with albendazol, in 2
      (8%) cysts underwent total involution, in 17 (68%) they presented positive
      changes, in one (4%) they remained unchanged and in 4 (16%) they progressed to
      type II, while 1 (4%) displayed negative evolutionary changes. Out of 39 cases
      under observation alone protocol, in 8 cases (21%) cysts underwent total
      involution, in 7 (18%) they presented positive changes, in 11 (28%) they remained
      unchanged, in 2 (5%) they progressed to Type II and in 11 (28%) they presented
      negative evolutionary changes and had to be included in the other protocol types.
      In this study, conventional surgery, was applied to 10% of detected cases. The
      combination of ultrasonographic screening and albendazol treatment showed
      promising results.

PMID- 15158685
TI  - Comparison of schistosome transmission in a single- and a double-cropped area in
      the rice irrigation scheme, 'Office du Niger', Mali.
AB  - Rice is becoming increasingly important as a staple food in West Africa and there
      is a need to increase production to meet the demand and one way to achieve this
      is to harvest two annual crops. It is possible that such intensified irrigation
      could affect transmission of schistosomes and this study attempts to compare
      schistosome transmission in single and double-cropped areas of an irrigation
      scheme, 'Office du Niger', in Mali. Double cropping has been practised for some
      years in the Niono area while in the Kolongotomo area still only a single crop is
      grown. Parasitological surveys conducted in 10 villages (5 from each of these 2
      areas) showed that Schistosoma haematobium was less prevalent in the area with
      single cropping than in the area with double cropping. In order to compare
      transmission patterns between the two areas, all human-water contact sites around
      four villages (two from each area) were identified and included in transmission
      studies. From August 1996 to June 1997, eight surveys were conducted, at
      intervals of approximately 45 days, in each of these sites to record density of
      the intermediate hosts, density of infected snails, environmental factors
      (especially density of aquatic macrophytes), and frequency of human-water
      contacts. Although the data provide useful information on transmission patterns
      in Niono and Kolongotomo areas, they fail to demonstrate clear-cut differences in
      snail population dynamics and transmission patterns between the two areas. A key
      element in snail habitats in both areas is the abundance of aquatic macrophytes,
      especially the submerged species. Snail control using environmental modification
      should focus on controlling these plants in human-water contact sites.

PMID- 15158686
TI  - Bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse
      granulocyte-macrophage colony-stimulating factor and an enkephalin fragment
      peptide Tyr-Gly-Gly.
AB  - We have earlier shown that recombinant mouse granulocyte-macrophage colony
      stimulating factor (rmGM-CSF) and methionine-enkephalin co-treatment can protect
      mice from malaria. We now report the bioimmunotherapeutic effect of rmGM-CSF and
      a synthetic enkephalin fragment peptide Tyr-Gly-Gly (TGG) co-treatment on blood
      induced Plasmodium berghei infection in Swiss mice. Mice were completely
      aparasitimic following co-treatment with rmGM-CSF (10.0 microg/kg) and TGG (2.0
      mg/kg x 3 per day, intraperitoneally (i.p.)) starting from day -1 to day +4;
      however, in monotherapy, neither of these agents showed any detectable
      bioimmunotherapeutic effect. Curiously, similar co-treatment with rmGM-CSF (10.0
      microg/kg) and higher doses of TGG (10.0 mg/kg) did not protect the mice. The
      combined bioimmunotherapeutic effect of these agents was abrogated by the
      separate administration each of rabbit neutralizing anti-rmGM-CSF antibody, non
      selective opioid receptor antagonist naltrexone (10.0 mg/kg x 6 per day, i.p.),
      and silica (3.0 mg per mouse, intravenously (i.v.)). The peritoneal and splenic
      macrophages from the protected mice showed a significant (P<0.05) increase in
      their pool-size and the phagocytic activity, ex vivo. Furthermore, the protected
      mice, as compared to the unprotected ones, showed a significant (P<0.05) maximum
      increase in their serum nitrate and nitrite, interferon-gamma (IFN-gamma), and
      tumor necrosis factor-alpha (TNF-alpha) levels in their splenic homogenates, on
      the day before the beginning of the resolution of parasitaemia. Selective
      inhibitors of both inducible (aminoguanidine) and all forms (L-N(G)-monomethyl
      arginine) of nitric oxide (NO) synthase, significantly (P<0.05) augmented the
      mortality of co-treated mice, suggesting the role of NO in protection. These data
      show that, in P. berghei-infected mice, co-treatment with rmGM-CSF and
      conditional doses of TGG can impart protection, apparently through partly NO
      dependent and macrophage-mediated mechanism(s).

PMID- 15158688
TI  - Surveillance of imported infectious diseases in Europe: report from the 4th
      TropNetEurop workshop.

PMID- 15158687
TI  - Detection of Schistosoma mansoni cercariae in plankton samples by PCR.
AB  - A PCR assay on the basis of a tandemly repeated DNA sequence was employed for the
      detection of Schistosoma mansoni in artificial plankton samples. It was highly
      specific, since as few as 1fg DNA from this species were sufficient to obtain a
      clear signal, while 10pg DNA of Schistosoma rodhaini were required and no PCR
      products were obtained with even 10ng DNA of planktonic organisms and any other
      trematode species tested. In areas with transmission of different Schistosoma
      species 10pg DNA should be used for amplification, which would allow detection of
      20 S. mansoni cercariae in 0.05g plankton without interference caused by DNA of
      other Schistosoma species. In other areas 10ng DNA from plankton samples can be
      amplified, detecting less than one S. mansoni cercaria specifically in 0.05g
      plankton. This assay might help to identify S. mansoni in samples from field
      studies, where a multitude of different organisms hinder a correct species
      identification.

PMID- 15158689
TI  - Zebrafish as a model host for streptococcal pathogenesis.
AB  - Streptococcal pathogens continue to evade concerted efforts to determine clear
      cut virulence mechanisms, although numerous genes have been implicated in
      pathogenesis. A single species can infect a diversity of tissues, suggesting the
      expression of specific virulence factors based on the local tissue environment or
      stage of infection. In an effort to identify the interactions that occur between
      the host and pathogen that lead to activation of virulence mechanisms and
      contribute to specific streptococcal disease states, we have developed a unique
      animal model, the zebrafish (Danio rerio), to characterize specific virulence
      mechanisms utilized within various tissues in vivo. We are using this model host
      to study infection by two streptococcal species that represent two forms of
      streptococcal disease: a natural pathogen of fish and humans, Streptococcus iniae
      and a human-specific pathogen, Streptococcus pyogenes. S. iniae primarily causes
      a fatal systemic disease in the zebrafish following intra-muscular injection,
      with similar pathologies to that seen in human infections caused by Streptococcus
      agalactiae and S. pneumoniae. While the fatal infection by S. pyogenes causes a
      locally spreading necrotic disease confined to the muscle with pathology similar
      to what is observed in a human infection of necrotizing fasciitis. By studying
      pathogens that are virulent for both fish and humans and that mediate disease
      states in the zebrafish that are identical to those found in human streptococcal
      infections, we will be able to identify common virulence strategies shared by a
      number of Gram-positive pathogens.

PMID- 15158690
TI  - Role of proteases in host cell invasion by Toxoplasma gondii and other
      Apicomplexa.
AB  - The process of invasion by apicomplexan parasites is a carefully coordinated
      process involving the regulated release of specialized secretory organelles.
      Several lines of evidence suggest that proteases are critical for the assembly
      and trafficking of organellar content proteins. Further, invasion is accompanied
      by cleavage and shedding of secreted proteins as host cell invasion occurs.
      Recent studies in Toxoplasma gondii and other Apicomplexa have led to the
      identification of proteases that may mediate these processing events. Among these
      are subtilases, subtilisin-like serine proteinases that have essential roles in
      processing of secreted proteins in prokaryotes and eukaryotes. Other studies
      suggest that cysteine proteinases or rhomboid proteases, a newly described class
      of serine proteinases, may be important. In addition to providing insights into
      the invasion process, characterization of invasion proteases may lead to
      identification of novel targets for antiparasitic chemotherapy.

PMID- 15158692
TI  - Neuronal nitric oxide synthase knock-out mice show impaired cognitive
      performance.
AB  - Nitric oxide (NO) plays a role in a series of neurobiological functions,
      underlying behavior and memory. The functional role of nNOS derived NO in
      cognitive functions, however, is elusive. We decided to study cognitive functions
      in the Morris water maze (MWM) and the multiple T-maze (MTM) in 3-month-old male
      nNOS-knock-out mice (nNOS KO). To study the influence of neurology and behavior,
      we performed tests in an observational battery, the rota-rod, the elevated plus
      maze (EPM), the open field (OF), and a social interaction test. In the memory and
      relearning task of the MWM, most nNOS KO failed whereas performing better in the
      MTM. nNOS KO displayed significantly increased frequency of grooming, center
      crossings, and entries into the center in the OF. The observational battery
      revealed significantly increased scores for touch-escape reaction, body position,
      locomotion, and pelvic- and tail-elevation together with reduced vocalization. In
      the EPM, the time spent in the closed arm and the grooming frequency were
      significantly increased whereas urination was absent. We conclude that nNOS KO
      show impaired spatial performance in the MWM and herewith confirm the role of
      nNOS in cognitive functions such as processing, maintenance, and recall of
      memory. It must be taken into account that the major behavioral findings of
      increased grooming and anxiety-related behaviors may have led to impaired
      function in the MWM. The fact that nNOS KO performed well in the MTM, reflecting
      a low stress situation points to the interpretation that nNOS inhibition affects
      cognitive functions under stressful conditions (MWM) only.

PMID- 15158691
TI  - Endogenous production and exogenous exposure to nitric oxide augment doxorubicin
      cytotoxicity for breast cancer cells but not cardiac myoblasts.
AB  - We studied the effect of nitric oxide (*NO) on the anticancer activity of
      doxorubicin. When MCF-7 human breast cancer cells were exposed to an aqueous
      solution of *NO delivered as a bolus 30 min prior to doxorubicin, the cytotoxic
      effect as measured in a clonogenic assay was increased (doxorubicin alone, 40%
      survival, doxorubicin plus *NO, 5% survival). The *NO donor diethylamine nitric
      oxide, but not inactivated donor, also yielded an increase in doxorubicin
      cytotoxicity. The sequence was important since the simultaneous application of
      *NO with doxorubicin yielded only a small augmentation of effect, and the
      exposure of the cells to doxorubicin prior to the *NO obliterated the
      augmentation. Prior depletion of glutathione by incubation of the cells for 24h
      with D,L-buthionine-S,R-sulfoximine (BSO) further increased the cytotoxicity so
      that BSO plus *NO plus doxorubicin killed all of the clones. MCF-7 cells
      transduced with inducible nitric oxide synthase gene (iNOS) through an adenoviral
      vector overexpressed iNOS and produced increased amounts of nitrite, an indicator
      of increased *NO production. These iNOS transduced cells were more susceptible to
      doxorubicin than vector control or wild-type cells. Cell cycle progression of
      iNOS transduced cells was not different from controls. Likewise, iNOS
      transduction resulted in no change in cellular glutathione levels. For
      comparison, we examined the effect of iNOS transduction on the sensitivity of MCF
      7 to edelfosine, a membrane-localizing anticancer drug without direct DNA
      interaction. Insertion of the iNOS had no effect on killing of the MCF-7 cells by
      this ether lipid class drug. We also tested the effect of iNOS transduction on
      doxorubicin sensitivity of H9c2 rat heart-derived myoblasts. We found no
      augmentation of cytotoxicity by *NO, and this observation offers potential
      therapeutic tumor selectivity by using *NO with doxorubicin. Therefore, we
      conclude that *NO produced intracellularly by iNOS overexpression or delivered as
      a bolus sensitizes human breast cancer cells in culture to doxorubicin, but not
      to a cardiac cell line or to edelfosine. This augmentation is not due to a
      modulation of cell cycle distribution or measurable cellular glutathione
      resulting from the transduction.

PMID- 15158693
TI  - Nitric oxide synthase inhibition during synaptic maturation decreases synapsin I
      immunoreactivity in rat brain.
AB  - During the development of the brain, nitric oxide and synapsins, the latter being
      phosphoproteins associated to presynaptic membrane vesicles, are abundant in
      presynaptic terminals and play important and similar roles in neurotransmitter
      release, morphogenesis, synaptogenesis, and synaptic plasticity. These mechanisms
      are fundamental for neuronal development and plasticity and constitute important
      factors for the formation of neuroanatomical structures. Neural nitric oxide
      synthase (nNOS), synapsin I, and nNOS adapter protein (CAPON) constitute a
      ternary complex necessary for specific NO and synapsin functions at a presynaptic
      level. It is not known whether NO absence may affect the presence and/or activity
      of synapsins during brain development. To understand the role of NO in
      synaptogenesis, we studied the effects of NOS inhibition on synapsin I expression
      at a postnatal stage. Rat pups were treated with a competitive NOS antagonist, N
      nitro-L-arginine methyl ester, from postnatal days 3 to 23. Control pups received
      exclusively an equivalent volume of saline solution. Histochemical and
      immunochemical techniques for NADPH-d and synapsin I, respectively, were carried
      out. NOS inhibition elicited a significant reduction in synapsin I immunoreactive
      density and NADPH-d activity in the brain in the analyzed areas-prefrontal
      cortex, hippocampus, and dorsal thalamus. These data show that the alterations
      originated by NO and synapsin deficiencies produce a diminution in synaptic
      density. Thus, functions that depend on the formation of synaptic connections
      such as learning and memory could be affected by NO deficiency.

PMID- 15158694
TI  - Echinococcus multilocularis laminated-layer components and the E14t 14-3-3
      recombinant protein decrease NO production by activated rat macrophages in vitro.
AB  - Echinococcus multilocularis and Echinococcus granulosus cause alveolar and cystic
      (unilocular) echinococcosis, respectively, in humans and animals. It is known
      that these parasites can affect, among other molecules, nitric oxide (NO)
      production by periparasitic host cells. Nevertheless, detailed dissection of
      parasite components specifically affecting cell NO production has not been done
      to date. We compare the effect of E. granulosus and E. multilocularis defined
      metacestode structural (laminated-layer associated) and metabolic (14-3-3
      protein, potentially related with E. multilocularis metacestode tumor-like
      growth) components on the NO production by rat alveolar macrophages in vitro. Our
      results showed that none of these antigens could stimulate macrophage NO
      production in vitro. However, a reversed effect of some Echinococcus antigens on
      NO in vitro production was found when cells were previously exposed to LPS
      stimulation. This inhibitory effect was found when E. multilocularis laminated
      layer (LL) or cyst wall (CW) soluble components from both species were used. Pre
      stimulation of cells with LPS also resulted in a strong, dose-dependent reduction
      of NO and iNOS mRNA production after incubation of cells with the E14t protein.
      Thus, the E. multilocularis 14-3-3 protein appears to be one of the components
      accounting for the suppressive effect of the CW and LL metacestode extracts.

PMID- 15158695
TI  - EPR quantification of vascular nitric oxide production in genetically modified
      mouse models.
AB  - With increasing use of genetically modified mice to study endothelial nitric
      oxide (NO) biology, methods for reliable quantification of vascular NO production
      by mouse tissues are crucial. We describe a technique based on electron
      paramagnetic resonance (EPR) spectroscopy, using colloid iron (II)
      diethyldithiocarbamate [Fe(DETC)2], to trap NO. A signal was seen from C57BL/6
      mice aortas incubated with Fe(DETC)2, that increased 4.7-fold on stimulation with
      calcium ionophore A23187 [3.45+/-0.13 vs 0.73+/-0.13au (arbitrary units)]. The
      signal increased linearly with incubation time (r(2) = 0.93), but was abolished
      by addition of N(G)-nitro-l-arginine methyl ester (L-NAME) or endothelial
      removal. Stimulated aortas from eNOS knockout mice had virtually undetectable
      signals (0.14+/-0.06 vs 3.17+/-0.21 au in littermate controls). However, the
      signal was doubled from mice with transgenic eNOS overexpression (7.17+/-0.76 vs
      3.37+/-0.43 au in littermate controls). We conclude that EPR is a useful tool for
      direct NO quantification in mouse vessels.

PMID- 15158696
TI  - Attenuation of iNOS mRNA exacerbates hypoperfusion and upregulates endothelin-1
      expression in hippocampus and cortex after brain trauma.
AB  - Nitric oxide (NO, a vasodilator) and endothelin-1 (ET-1, a powerful
      vasoconstrictor) participate in the regulation of brain's microcirculation
      influencing each other's expression and synthesis. Following injury to the brain,
      NO is derived largely from the inducible form of nitric oxide synthase (iNOS). We
      used Marmarou's model of traumatic brain injury (TBI) to study the cerebral blood
      flow and expression (mRNA) of ET-1 in rats that were pretreated with antisense
      iNOS oligodeoxynucleotides (ODNs). Intracerebroventricular application of iNOS
      ODNs resulted in reduced synthesis of iNOS as detected by Western blot analysis.
      The cerebral blood flow (measured by laser Doppler flowmetry), generally
      decreased after TBI, was further markedly reduced in the treated animals and
      remained at low levels up to 48 h post-TBI. The expression of ET-1 (detected by
      in situ hybridization in cortex and hippocampus) was increased 2-3-fold following
      TBI alone and this increase reached 5-6-fold in animals pretreated with antisense
      iNOS ODNs. The results indicate that most likely, NO, generated primarily by
      iNOS, suppresses ET-1 production and that a decrease of NO results in
      upregulation of ET-1 via transcriptional and translational mechanisms. Increased
      availability of ET-1 at the vascular bed and the neuropil may contribute to the
      altered microvascular reactivity and reduced perfusion of the brain following
      TBI.

PMID- 15158697
TI  - A novel potent inhibitor of inducible nitric oxide inhibitor, ONO-1714, reduces
      intestinal ischemia-reperfusion injury in rats.
AB  - The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS)
      may contribute to the pathophysiology of intestinal injury induced by ischemia
      reperfusion. The aim of the present study was to examine the effect of selective
      iNOS inhibition by a cyclic amidine analogue, ONO-1714, on reperfusion-induced
      small intestinal injury and inflammation in rats. Intestinal damage was induced
      in male Sprague-Dawley rats by clamping both the superior mesenteric artery and
      the celiac trunk for 30 min, followed by reperfusion. The luminal nitrite
      concentration in the small intestine was measured by Griess reaction and the iNOS
      mRNA expression by RT-PCR. The severity of the intestinal mucosal injury and
      inflammation were evaluated by several biochemical markers and by the
      histological findings. The rats which were killed after ischemia-reperfusion had
      increased luminal concentrations of nitrite and iNOS mRNA expression, in addition
      to severe intestinal inflammation characterized by significant increases in
      myeloperoxidase activity, a marker of neutrophil infiltration, and by the mucosal
      content of CINC-1 cytokine, a neutrophil chemotactic cytokine. Administration
      with ONO-1714 significantly inhibited the luminal NO production. Reperfusion
      after 30-min ischemia resulted in an increase in luminal protein and hemoglobin
      concentrations, with levels reaching a maximum after 60 min of reperfusion. In
      contrast, pre-treatment with ONO-1714 2h before the ischemia inhibited the
      increases in luminal protein and hemoglobin concentration in a dose-dependent
      manner (0.001-0.1mg/kg). The contents of the thiobarbituric acid-reactive
      substances (a marker of oxidative lipid peroxidation) were significantly
      increased by ischemia-reperfusion, and this increase was reduced by ONO-1714.
      After reperfusion, the increase in tissue-associated myeloperoxidase activity, an
      index of neutrophil infiltration, was significantly inhibited by pre-treatment
      with ONO-1714. ONO-1714 also inhibited increases in intestinal CINC-1 protein and
      mRNA expression, as determined by ELISA and RT-PCR, respectively. In conclusion,
      the improvement of reperfusion-induced intestinal injury by ONO-1714 suggested
      that an excess of NO, produced by iNOS, may have contributed to the
      initiation/amplification of intestinal inflammatory injury by various mechanisms,
      including nitrosative and oxidative damage as well as the enhancement of
      inflammatory cytokine release.

PMID- 15158698
TI  - Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and
      maximal electroshock seizure models.
AB  - There is emerging evidence to support the efficacy of some antiepileptic drug
      (AED) combinations in refractory epilepsy. Definitive clinical studies are,
      however, difficult to perform. Experimental seizure models can be employed to
      identify potentially useful combinations for subsequent clinical evaluation. We
      have investigated the anticonvulsant effects of topiramate (TPM) in combination
      with 13 other AEDs in the pentylenetetrazol (PTZ) and maximal electroshock (MES)
      seizure models. Single drugs and combinations were administered by
      intraperitoneal injection and anticonvulsant effects determined at 1-hour post
      dosing. TPM was without significant effect in the PTZ test. In contrast,
      phenobarbital, primidone, ethosuximide, sodium valproate, felbamate and tiagabine
      all increased the latency to the first generalised seizure. Combinations of TPM
      and active adjunctive drug were universally effective. Combinations of TPM with
      clobazam, lamotrigine and levetiracetam were also anticonvulsant, despite the
      inactivity of the constituent compounds when administered alone. TPM reduced the
      incidence of MES-induced seizures in a dose-dependent manner, as did
      phenobarbital, phenytoin, primidone, carbamazepine, sodium valproate, clobazam,
      lamotrigine, felbamate and tiagabine. All combination treatments were similarly
      effective. These findings suggest that combinations of TPM with lamotrigine and
      levetiracetam may demonstrate anticonvulsant synergism and merit further
      investigation in additional model systems and with recourse to more quantitative
      mathematical analysis.

PMID- 15158700
TI  - The specialist nurse role in the treatment of refractory epilepsy.
AB  - The main aim of epilepsy treatment is rapid and complete control of seizures
      without antiepileptic drug (AED) side effects. This outcome is achieved in 60-70%
      of newly diagnosed patients. In refractory epilepsy, new AEDs render some
      additional patients seizure free but make treatment more complex. The choice of
      AEDs, their differing pharmacokinetics, efficacy, tolerability and potential
      interactions are multiplied. Up to of 75% of patients develop AED side effects,
      most AEDs can cause paradoxical reactions, and when AED doses are changed
      seizures may worsen. Despite the increased complexity of epilepsy treatment and
      the biomedical and psychosocial consequences of uncontrolled seizures, many
      patients have difficulty accessing specialist services. A service that involves
      the epilepsy nurse specialist (ENS) giving patients and General Practitioners
      (GPs) free access to treatment advice has recently been established to improve
      care. Over a 2-week period 60 treatment-related telephone or outpatient
      consultations were provided out of a total of 124 contacts. Changes to the AED
      regimen were implemented in 44/60, and the GP was notified by letter in 31/44.
      The audit results are presented and epilepsy treatment including AED efficacy,
      tolerability, interactions and side effects are discussed.

PMID- 15158699
TI  - EEG in childhood absence epilepsy.
AB  - We performed a longitudinal clinico-electroencephalographic study of 23 children
      who were diagnosed as having absence epilepsy on their initial visits to our
      facility and we analysed those factors which lead to an unfavourable prognosis.
      SUBJECTS AND METHODS: We divided the 23 patients into three groups according to
      their clinical courses: Group A: eight patients who responded well to the therapy
      and became seizure free without relapse of epileptic discharges on EEGs; Group B:
      thirteen patients who suffered from relapse of epileptic discharges on EEGs
      despite clinical seizure cessation; Group C: two patients who continued to suffer
      from seizures. RESULTS: (1) Fifty-six percent of all patients had focal epileptic
      discharges, including a surprising 63% of patients in Group A. (2) "Lead in" in
      the ictal EEGs and automatisms during seizures were most commonly observed in
      patients in Group B, although there were no significant differences between the
      three groups. (3) The epilepsy of one patient in Group C evolved into complex
      partial seizures or absence status during her clinical course. She seemed to
      suffer from so-called "frontal absence", despite the fact that her initial EEG
      did not show any focal abnormalities. (4) Patients in Group B were treated with
      lower AED dosages than those in Group A. In addition, one patient in Group C was
      treated irregularly. CONCLUSION: We conclude that it is not uncommon for patients
      with absence epilepsy to show focal abnormalities on EEGs and clinical ictal
      automatisms. Thus, the existence of clinical ictal automatisms and focal signs in
      electroencephalographic features are not sufficient indicators of the final
      outcome. Furthermore, it appears that regular and adequate drug therapy is
      important for a favourable prognosis.

PMID- 15158701
TI  - How can paediatric epilepsy services best be delivered in secondary care?
AB  - OBJECTIVE: To produce practical evidence-based guidelines for the management of
      paediatric epilepsy in secondary care settings. DESIGN: Question-specific
      systematic literature review and local service audit. MAIN OUTCOME MEASURES:
      Grade of recommendation for specific management issues. RESULTS: There is little
      good quality research to support many existing epilepsy guidelines for secondary
      care. CONCLUSION: Practical guidelines for the provision of children's epilepsy
      services can be evidence influenced but until more relevant research is
      undertaken, not evidence based.

PMID- 15158702
TI  - Diffusion changes suggesting predominant vasogenic oedema during partial status
      epilepticus.
AB  - Diffusion-weighted imaging (DWI) has demonstrated a focal area of cytotoxic
      oedema during partial status epilepticus (PSE). However, vasogenic oedema related
      to the breakdown of the blood-brain-barrier (BBB) and ictal hyperperfusion could
      be the predominant DWI findings in the epileptogenic area during PSE. We report a
      case of PSE with ictal aphasia, right hemiparesis, and repetitive focal motor
      seizure of the right side. T2-weighted image (T2WI) and apparent diffusion
      coefficient (ADC) maps obtained during PSE showed an increased signal in the left
      temporo-parietal area, indicative of vasogenic oedema. EEG documented the ictal
      activities and single photon emission tomography (SPECT) showed asymmetrically
      increased perfusion in the corresponding area. Follow-up T2WI, DWI, and ADC maps
      obtained 3 months later showed the disappearance of the previous abnormalities.
      However, T2WI showed cortical atrophy and newly developed white matter changes in
      the corresponding area. This case shows that DWI findings may be variable during
      PSE, dependent on the predominance of cytotoxic and vasogenic oedema.

PMID- 15158703
TI  - Aetiology of epilepsy in surgically treated patients in China.
AB  - The aim of this retrospective, multicenter clinical study was to evaluate the
      aetiology of epilepsy in surgically treated patients in China. The detailed
      clinical records of all intractable partial epilepsy (IPE) were reviewed in five
      tertiary referral centres from June 1991 to June 2000. 1650 patients (927 males,
      723 females) were recruited. 41.4% had aetiological factors, including the
      histories of major brain trauma (20.9%), febrile seizure (6.5%), meningitis
      (5.4%), encephalitis (5.0%), prenatal distress (2.1%), birth trauma (0.8%) and
      family history of seizure (0.7%). The pathological lesions were divided into
      eight groups according to the nature of the lesion: scar (19.2%), vascular
      malformations (VM) (17.7%), hippocampal sclerosis (HS) (16.2%), tumours (15.0%),
      gliosis (12.1%), neuronal migration disorders (NMDs) (7.4%), intracranial
      infection (4.5%), and other lesions (7.9%). In conclusion, effective management
      of these aetiological factors and pathological lesions may be essential to deal
      with IPE. Scar, HS, VM, NMDs are the most likely consequences of antecedent
      morbid events.

PMID- 15158704
TI  - Heraldic seizure.
AB  - BACKGROUND: The term heraldic seizures indicates epileptic seizures caused by
      cerebrovascular disease, believed to be triggered by silent ischemia and
      occurring before a stroke. This fact widens the spectrum of possible
      interrelations between epilepsy and cerebrovascular disease outside the well
      known context of post-stroke epilepsy. METHODS: This is a case report of a
      healthy 67-year-old male who had a new onset epileptic seizure prior to a lobar
      intracerebral hemorrhage (ICH). This man began to suffer myoclonic jerks in his
      left arm which progressed to a generalized tonic-clonic seizure. At the emergency
      area the physical and neurological examination were unremarkable and a CT scan
      was normal. The next day the patient developed left hemiparesis, hemianopsia and
      confusion and a new CT scan showed right parietal-occipital ICH. CONCLUSIONS:
      This case report exemplifies the concept of heraldic seizures, showing a patient
      who had a focal seizure preceding an intracerebral hemorrhage. Our etiologic
      diagnostic work led us to a diagnosis of probable amyloid angiopathy. We suggest
      that cerebral amyloid angiopathy (CAA) may be the underlying cause, since it may
      be the origin of both the late event (ICH) and the heralding seizures, resulting
      from concurrent ischemia.

PMID- 15158705
TI  - Illness representations among people with non-epileptic seizures attending a
      neuropsychiatry clinic: a qualitative study based on the self-regulation model.
AB  - A qualitative study was carried out in order to investigate illness
      representations of people with non-epileptic seizures (NES) in relation to
      Leventhal's self-regulation or common sense model. Nine participants with NES
      took part in semi-structured interviews and transcripts were analysed using an
      approach from interpretative phenomenological analysis. Data were coded according
      to the five elements of the self-regulation model (identity, cause, time-line,
      consequences, controllability) and two additional themes. Particularly evident
      was participants' confusion about their experience, what to call their condition,
      and its cause. It was therefore difficult for participants to express clear ideas
      about the time-line of their illness and its control or cure. Also evident was a
      tendency to categorise illness in dualistic terms as either organic or
      psychological. There was some dissatisfaction with doctors where ideas about the
      nature of the illness did not match. It is concluded that a clear idea of illness
      identity and cause may be necessary for successful management.

PMID- 15158706
TI  - Effect of vagus nerve stimulation on adults with pharmacoresistant generalized
      epilepsy syndromes.
AB  - INTRODUCTION: Although vagus nerve stimulation (VNS) therapy is approved for the
      treatment of partial onset seizures, its efficacy for generalized seizures has
      not been fully evaluated. This Investigational Device Exemption assessed the
      outcome of VNS therapy among patients with generalized epilepsy syndromes.
      METHODS: Sixteen patients with pharmacoresistant generalized epilepsy syndromes
      and stable antiepileptic drug (AED) regimens were implanted with the VNS therapy
      device and were evaluated for changes in seizure frequency and type between
      baseline and follow-up of 12-21 months. RESULTS: The patients experienced a
      statistically significant overall median seizure frequency reduction of 43.3% (P
      = 0.002, Wilcoxon signed rank test) after 12-21 months of VNS therapy. Types of
      seizures that may involve a fall or collapse decreased with reductions in the
      frequency of myoclonic (60% reduction, n = 9; P = 0.016, Wilcoxon signed rank
      test), tonic (75% reduction, n = 8, NS), atonic (98.6%, n = 3, NS), and clonic
      seizures (86.7%, n = 1, NS). CONCLUSION: The benefits of reduced seizure
      frequency and reduced risk of injury merit consideration of VNS therapy for
      patients with pharmacoresistant generalized seizure syndromes.

PMID- 15158707
TI  - Ictal chronology and interictal spikes predict perfusion patterns in temporal
      lobe epilepsy: a multivariate study.
AB  - Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal
      SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the
      lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive
      variables for the occurrence of TPP and APP. Fifty-one TLE patients were
      submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and
      multivariate (MVA) analysis were performed upon clinical data, distribution of
      interictal spikes, and ictal chronology of seizures. From MVA, a final predictive
      model (FPM) was determined to better predict TPP and APP. Forty patients showed
      TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in
      the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P =
      0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the
      electrographic seizure occurring after completion of tracer injection, and longer
      clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic
      clonic seizures did not result in more APP. We concluded that analysis of ictal
      SPECT in TLE requires the knowledge of TPP and APP, the distribution of
      interictal spikes on temporal lobes and the ictal chronology of seizures. BIS
      showed that beyond a more complex epileptogenicity and seizure propagation, they
      may also lead to APP.

PMID- 15158708
TI  - Focal nonconvulsive status epilepticus associated to PLEDs and intense focal
      hyperemia in an AIDS patient.
AB  - PURPOSE: Periodic lateralised epileptiform discharges (PLEDs) can be seen
      associated to nonconvulsive status epilepticus (NCSE), although their
      pathophysiological meaning remains questionable. Functional neuroimaging has
      suggested that, in this setting, PLEDs may indeed be an ictal pattern. In this
      report we describe perfusional changes in a patient with AIDS, PLEDs and NCSE.
      METHODS: A 37-year-old man with AIDS, cryptococcosis and recurrent epileptic
      seizures was admitted. After initial treatment, he remained comatose, and had MRI
      and serial EEG recordings performed. Technetium-99m-ethyl cysteinate dimer (99mTc
      ECD) SPECT scans were also obtained, before and after continuous benzodiazepine
      infusion. RESULTS: EEG disclosed PLEDs over the right fronto-polar region while
      MRI revealed meningeal thickening and scattered unspecific findings. SPECT
      revealed marked focal hyperperfusion overlapping the areas with PLEDs, both
      resolved after continuous midazolam infusion and clinical improvement.
      CONCLUSIONS: This report demonstrates association of PLEDs, NCSE, and focal
      hyperperfusion on SPECT, additionally supporting the concept of PLEDs as an ictal
      pattern. Considering that status epilepticus may eventually not be detected by
      conventional approaches alone, we advocate the use of functional neuroimaging to
      assess suspected patients with impaired consciousness.

PMID- 15158709
TI  - Structure, function, and mechanism of ribonucleotide reductases.
AB  - Ribonucleotide reductase (RNR) is the enzyme responsible for the conversion of
      ribonucleotides to 2'-deoxyribonucleotides and thereby provides the precursors
      needed for both synthesis and repair of DNA. In the recent years, many new
      crystal structures have been obtained of the protein subunits of all three
      classes of RNR. This review will focus upon recent structural and spectroscopic
      studies, which have offered deeper insight to the mechanistic properties as well
      as evolutionary relationship and diversity among the different classes of RNR.
      Although the three different classes of RNR enzymes depend on different metal
      cofactors for the catalytic activity, all three classes have a conserved cysteine
      residue at the active site located on the tip of a protein loop in the centre of
      an alpha/beta-barrel structural motif. This cysteine residue is believed to be
      converted into a thiyl radical that initiates the substrate turnover in all three
      classes of RNR. The functional and structural similarities suggest that the
      present-day RNRs have all evolved from a common ancestral reductase.
      Nevertheless, the different cofactors found in the three classes of RNR make the
      RNR proteins into interesting model systems for quite diverse protein families,
      such as diiron-oxygen proteins, cobalamin-dependent proteins, and SAM-dependent
      iron-sulfur proteins. There are also significant variations within each of the
      three classes of RNR. With new structures available of the R2 protein of class I
      RNR, we have made a comparison of the diiron centres in R2 from mouse and
      Escherichia coli. The R2 protein shows dynamic carboxylate, radical, and water
      shifts in different redox forms, and new radical forms are different from non
      radical forms. In mouse R2, the binding of iron(II) or cobalt(II) to the four
      metal sites shows high cooperativity. A unique situation is found in RNR from
      baker's yeast, which is made up of heterodimers, in contrast to homodimers, which
      is the normal case for class I RNR. Since the reduction of ribonucleotides is the
      rate-limiting step of DNA synthesis, RNR is an important target for cell growth
      control, and the recent finding of a p53-induced isoform of the R2 protein in
      mammalian cells has increased the interest for the role of RNR during the
      different phases of the cell cycle.

PMID- 15158710
TI  - Protein disulfide isomerase.
AB  - During the maturation of extracellular proteins, disulfide bonds that chemically
      cross-link specific cysteines are often added to stabilize a protein or to join
      it covalently to other proteins. Disulfide formation, which requires a change in
      the covalent structure of the protein, occurs as the protein folds into its three
      dimensional structure. In the eukaryotic endoplasmic reticulum and in the
      bacterial periplasm, an elaborate system of chaperones and folding catalysts
      ensure that disulfides connect the proper cysteines and that the folding protein
      does not make improper interactions. This review focuses specifically on one of
      these folding assistants, protein disulfide isomerase (PDI), an enzyme that
      catalyzes disulfide formation and isomerization and a chaperone that inhibits
      aggregation.

PMID- 15158711
TI  - Thermodynamic stability of the C-terminal domain of the human inducible heat
      shock protein 70.
AB  - The stability of the substrate-binding region of human inducible Hsp70 was
      studied by a combination of spectroscopic and calorimetric methods. Thermal
      denaturation of the protein involves four accessible states: the native state,
      two largely populated intermediates, and the denatured state, with transition
      temperatures of 52.8, 56.2 and 71.2 degrees C, respectively, at pH 6.5. The
      intermediate spectroscopic properties resemble those of molten globules but they
      still retain substantial enthalpy and heat capacity of unfolding. Moreover, the
      similar heat capacities of the first intermediate and the native state suggests
      that the hydrophobic core of the intermediate would be highly native-like and
      that its formation would involve an increased disorder in localized portions of
      the structure rather than formation of a globally disordered state. The structure
      of the C-terminal of Hsp70 is destabilized as the pH separates from neutrality.
      The intermediates become populated under heat shock conditions at acidic and
      basic pHs. Denaturation by guanidine chloride also indicated that the protein
      undergoes a sequential unfolding process. The free energy change associated to
      the loss of secondary structure at 20 degrees C (pH 6.5) is 3.1 kcal.mol(-1) at
      high salt conditions. These values agree with the free energy changes estimated
      from differential scanning calorimetry for the transition between the second
      intermediate and the final denatured state.

PMID- 15158712
TI  - PLUNC in human nasal lavage fluid: multiple isoforms that bind to
      lipopolysaccharide.
AB  - Here, we demonstrate the presence of multiple isoforms of palate lung nasal
      epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were
      separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of
      the proteins was performed using MALDI-TOF MS (matrix assisted laser
      desorption/ionization time of flight mass spectrometry) of tryptic and
      asparginase cleavages. The identification was verified by amino acid sequencing
      after analysis of collision-induced dissociation (CID) fragmentation spectra with
      nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift
      after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms
      is glycosylated. We also demonstrate that PLUNC in NLF binds to
      lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF
      only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These
      results show that PLUNC is expressed as multiple LPS-binding isoforms in human
      NLF. The possibility that PLUNC may play a role in the innate immune response of
      the upper airways is inferred.

PMID- 15158713
TI  - Two extracellular proteins with alkaline peroxidase activity, a novel cytochrome
      c and a catalase-peroxidase, from Bacillus sp. No.13.
AB  - A novel cytochrome c and a catalase-peroxidase with alkaline peroxidase activity
      were purified from the culture supernatant of Bacillus sp. No.13 and
      characterized. The cytochrome c exhibited absorption maxima at 408 nm (Soret
      band) in its oxidized state, and 550 (alpha-band), 521 (beta-band), and 415
      (Soret band) nm in its reduced state. The native cytochrome c with a relative
      molecular mass of 15,000 was composed of two identical subunits. The cytochrome c
      showed over 50 times higher peroxidase activity than those of known c-type
      cytochromes from various sources. The optimum pH and temperature of the
      peroxidase activity were about 10.0 and 70 degrees C, respectively. The
      peroxidase activity is stable in the pH range of 6.0 to 10.8 (30 degrees C, 1-h
      treatment), and at temperatures up to 80 degrees C (pH 8.5, 20-min treatment).
      The heme content was determined to be 1 heme per subunit. The amino acid sequence
      of the cytochrome c showed high homology with those of the c-type cytochromes
      from Bacillus subtilis and Bacillus sp. PS3. The catalase-peroxidase showed high
      catalase activity and considerable peroxidase activity, the specific activities
      being 55,000 and 0.94 micromol/min/mg, respectively. The optimum pH and
      temperature of the peroxidase activity were in the range of 6.4 to 10.1 and 60
      degrees C, respectively. The catalase-peroxidase showed a lower K(m) value (0.67
      mM) as to H(2)O(2) than known catalase-peroxidases.

PMID- 15158714
TI  - Circular dichroism and fluorescence of a tyrosine side-chain residue monitors the
      concentration-dependent equilibrium between U-shaped and coiled-coil
      conformations of a peptide derived from the catalytic core of HIV-1 integrase.
AB  - The peptide denoted K159 (30 residues) derives from the catalytic core (CC)
      sequence of HIV-1 integrase (IN, residues 147-175). In the crystal structure of
      CC, the corresponding segment belongs to the alpha4 helix (residues 148-168,
      including residues Glu 152, Lys 156 and Lys 159, crucial for enzyme activity and
      DNA recognition), a loop (residues 169-171) and a part of the alpha5 helix (171
      175), involved in enzyme dimerization. We used the fluorescence and the circular
      dichroism (CD) properties in the near-UV of the aromatic side chain of a tyrosine
      residue added at the C-terminal end of K159 in order to analyze the behavior of
      the concentrated and diluted peptide in aqueous trifluoroethanol (TFE), in an
      attempt to connect the information obtainable at high (NMR), medium (CD) and low
      (fluorescence) concentrations of the peptide. Altogether, the C-terminal tyrosine
      residue provided indirect information on the global conformation of K159 and on
      the local orientation and environment of the residue. The propensity of TFE to
      stabilize alpha-helical conformations in peptides was confirmed in CD and
      fluorescence experiments at relatively high (20-160 microM) and low (2-16 microM)
      concentrations, respectively. At relatively high concentration, stabilization of
      the peptide into alpha-helical conformation favored its auto-association likely
      in parallel coiled-coil dimers, as pointed out in our previous work [Eur. J.
      Biochem. 253 (1998) 236]. This was further confirmed by ANS (1-anilinonaphtalene
      8-sulfonic acid) analysis and fluorescence temperature coefficient measurement.
      With diluted K159, a Stern-Volmer analysis with positively and negatively charged
      quenchers indicated that, when the intermolecular interactions were absent, the
      tyrosine was in a positively charged environment, as if the peptide folded into a
      U-shaped conformation similar to that present in the crystal structure of the
      enzyme.

PMID- 15158716
TI  - The two subfamilies of rice glutelin differ in both primary and higher-order
      structures.
AB  - Rice glutelin, which accounts for 70-80% of the total proteins of the seeds,
      consists of two nutritionally different subfamilies (A and B types). Although the
      similarity in primary sequences between the two subfamilies is as high as 60%, we
      established conditions to discriminate the two subfamilies when low amounts of
      antigen are analyzed by immunoblot methods. The glutelin alpha polypeptides can
      be resolved into six bands labeled alpha1 to alpha6 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Gel filtration analysis showed
      that glutelin exists as a polymerized and a smaller molecular weight form.
      Immunoblot analysis of SDS-PAGE resolved polypeptides showed that alpha2, alpha3,
      and alpha4 are an A type and that these A types as well as alpha1, a B type, are
      polymerized. The polymerization tendency clearly differed between the two
      subfamilies except for alpha1, which may be derived from GluB-4 as suggested by
      analysis using Escherichia coli expression systems of glutelin cDNA regions
      corresponding to alpha polypeptides. GluB-4 and all the A type subunits have an
      extra Cys residue in the hypervariable regions, corresponding to the C-terminal
      region of alpha polypeptide. Accordingly, the extra Cys residue is hypothesized
      to be responsible for the polymerization of glutelin.

PMID- 15158715
TI  - Saturation mutagenesis, complement selection, and steady-state kinetic studies
      illuminate the roles of invariant residues in active site loop I of the
      hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi.
AB  - Hypoxanthine phosphoribosyltransferases (HPRTs) are potential drug targets in the
      treatment of diseases caused by parasites. Also, defects in the human HPRT can
      result in gouty arthritis or Lesch-Nyhan syndrome. Active site loop I of HPRTs
      has been implicated in interactions between enzyme subunits that can influence
      the relative efficiencies of forward and reverse reactions, but the functional
      roles for invariant loop I residues (analogous with human Leu67 and Gly69) are
      poorly understood. Herein, saturation mutagenesis, complement selection, and
      steady-state kinetics were used to investigate the functional roles for Leu67 and
      Gly69. Seventy clones from a library of mutants were sequenced and more than 30
      different mutations, or combinations of mutations, were identified. Several
      recombinant HPRTs with mutations at positions 67 and/or 69 supported the growth
      of a bacterial auxotroph on selective media, but only two of the mutants (L67M
      and G69S) could be recovered in the soluble fraction from bacteria induced to
      over-express the enzyme. The results of steady-state kinetic studies for L67M are
      consistent with the side chain of this residue participating in hydrophobic
      interactions between dimer subunits that are important for the proper positioning
      of main chain atoms that influence enzyme chemistry and the binding of PRPP, PPi,
      and hypoxanthine. The results for mutations at position 69 are consistent with
      only hydrogen or a small polar side chain being tolerated at this site. Kinetic
      studies of G69S suggest that side chains of residues at position 69 that project
      into the active site likely interfere with the binding of PRPP and PPi, as well
      as the positioning of a metal ion that indirectly influences the binding of
      purine bases and purine moieties of nucleotide substrates.

PMID- 15158717
TI  - Mutagenesis of the three conserved valine residues: consequence on the
      foldability of insulin.
AB  - Natural polypeptide chain usually can spontaneously fold into tightly compact
      native structure. This capability is the so-called foldability. However, how the
      foldability is encoded in the polypeptide chain is still poorly understood. The
      structure of insulin has been well solved and extensively investigated.
      Therefore, insulin provides a good model for investigating the role of individual
      residue to the sequence foldability. In insulins from different species there are
      three highly conserved Val residues (A3Val, B12Val, and B18Val), but their
      contribution to the insulin foldability is still unknown. Here, a single-chain
      insulin (PIP) was used to investigate the contribution of the three conserved
      valine residues to the foldability. Five PIP mutants, [A3S]PIP, [A3T]PIP,
      [B12A]PIP, [B18T]PIP, and [B18L]PIP, were used in the studies, and their
      structural changes, secretion efficiency, structural stability, disulfide
      stability, and in vitro refolding efficiency were analyzed. The effects of the
      mutations on the PIP foldability are multifold: as a whole, mutation of A3Val has
      only moderate effect; while mutation of B12Val has significant detriment;
      hydrophobic replacement of B18Val is more tolerant than hydrophilic substitution
      as foldability is concerned. Therefore, the three highly conserved valine
      residues have different contributions to the insulin foldability, and their
      contribution might be ranked as B12Val>B18Val>A3Val.

PMID- 15158718
TI  - Molecular cloning, functional expression in Escherichia coli and enzymatic
      characterisation of a cysteine protease from white clover (Trifolium repens).
AB  - This paper presents the cloning and biochemical characterisation of the cysteine
      protease Tr-cp 14 from white clover (Trifolium repens). The predicted amino acid
      sequence of Tr-cp 14 is 71%, 74% and 74% identical to the cysteine proteases XCP1
      and XCP2 from Arabidopsis thaliana, and p48h-17 from Zinnia elegans,
      respectively. These cysteine proteases have previously been shown to be involved
      in programmed cell death during tracheary element differentiation. The precursor
      polypeptide of Tr-cp 14 was expressed in Escherichia coli, purified from
      inclusion bodies and refolded. The precursor polypeptide could be processed to
      its active mature form autocatalytically at pH 5.0 and had a requirement for 20
      mM l-cysteine for optimal activity. Mature Tr-cp 14 showed a preference for
      synthetic aminomethylcoumarin substrates with either Leu or Phe in the P2
      position when tested with Arg in P1. A substrate with Arg in both the P1 and P2
      position was not accepted as substrate.

PMID- 15158719
TI  - Effect of pH and ionic strength on the cytolytic toxin Cyt1A: a fluorescence
      spectroscopy study.
AB  - Cyt1A is a cytolytic toxin produced by Bacillus thuringiensis var. israelensis.
      Due to its toxicity in vivo against mosquitoes and black flies, it is used as an
      environmentally friendly insecticide, although its mode of action is not
      completely understood. The toxin is membrane-active, but its membrane-bound
      conformation is unknown. In the absence of direct structural data, fluorescence
      spectroscopy was used to obtain indirect information on Cyt1A conformation
      changes in the environment mimicking the vicinity of the lipid membrane (lower pH
      and increased ionic strength). With decreasing pH, Cyt1A's surface hydrophobicity
      increased, which is consistent with an increased interaction with model membranes
      at low pH values, as observed previously. The pK(a) value of this conformation
      change is 4.4+/-0.1. Intrinsic tryptophan fluorescence decreased with decreasing
      pH, and the pK(a) value was the same as the one determined with synthetic probes.
      The protein has two types of hydrophobic binding sites, and at low pH these sites
      bind more probe molecules (bis-ANS) with a higher affinity than at pH 7.4. When
      bound to the lipid, the toxin exhibited conformation similar to the molten
      globule state and showed some characteristics also observed at low pH. However,
      the conformation of the lipid-bound toxin did not depend on pH. Neutral salts
      like NaCl and KCl induced conformational changes at neutral pH, but not at low
      pH. These changes were most probably due to specific interactions of the salt
      ions with the charged amino acids on the protein surface rather than due to
      general effects such as Hofmeister and Debye-Huckel. Our results might contribute
      to elucidating the mode of action of Cyt1A, and perhaps also to improving the
      formulation of the insecticidal preparations.

PMID- 15158721
TI  - Effect of reactive site loop elongation on the inhibitory activity of C1
      inhibitor.
AB  - The serine protease inhibitor C1-Inhibitor (C1-Inh) inhibits several complement-
      and contact-system proteases, which play an important role in inflammation. C1
      Inh has a short reactive site loop (RSL) compared to other serpins. RSL length
      determines the inhibitory activity of serpins. We investigated the effect of RSL
      elongation on inhibitory activity of C1-Inh by insertion of one or two alanine
      residues in the RSL. One of five mutants had an increased association rate with
      kallikrein, but was nevertheless a poor inhibitor because of a simultaneous high
      stoichiometry of inhibition (>10). The association rate of the other variants was
      lower than that of wild-type C1-Inh. These data suggest that the relatively weak
      inhibitory activity of C1-Inh is not the result of its short RSL. The short RSL
      of C1-Inh has, surprisingly, the optimal length for inhibition.

PMID- 15158720
TI  - Synthetic peptides corresponding to ligand-binding region of death receptors,
      DR5, Fas, and TNFR, specifically inhibit cell death mediated by the death
      ligands, respectively.
AB  - Apoptosis as well as cell growth and cell differentiation play an important role
      in the maintenance of homeostasis in multicellular organisms. Disruption of
      apoptosis causes serious diseases, such as cancer, chronic inflammatory diseases,
      and autoimmune diseases; therefore, the control of apoptosis is one of the most
      promising therapeutic approaches to these apoptosis-disrupted diseases. Apoptosis
      is mediated by soluble factors, which belong to the TNF superfamily, such as TNF
      alpha, FasL, and TRAIL. Here, we report that we deduced ligand-binding domains
      based on the structure of apoptosis ligand-receptor complex, and the synthetic
      peptide corresponding to residues 91-102 of DR5 indeed showed specific binding to
      TRAIL molecule and inhibited TRAIL-induced cell death both in L929 cells and in
      HeLa cells. The other death receptor-derived peptides, which are the
      corresponding regions of TNFR1 and Fas, also showed specific binding to TNF-alpha
      and FasL and inhibited the ligand-induced cell death, respectively. These results
      suggest that the position of the ligand-binding region is conserved among these
      death-receptor family members, whereas the primary amino acid sequence determines
      ligand specificity.

PMID- 15158722
TI  - Lack of evidence for phosphorylation of Arabidopsis thaliana PII: implications
      for plastid carbon and nitrogen signaling.
AB  - The PII signal transduction protein is regulated by covalent modification in most
      prokaryotic organisms. In enteric bacteria PII is uridylylated on a specific
      tyrosine residue in the T-loop region, while in certain cyanobacteria it is
      phosphorylated at the serine residue two positions away from the equivalent
      modified tyrosine of enteric bacteria. Covalent modification functions primarily
      to signal cellular nitrogen status in prokaryotes. Here we have examined the
      phospho-status of Arabidopsis thaliana PII under various growth conditions
      employing a variety of techniques, including in vivo labeling, phosphospecific
      antibodies, protein phosphatase treatment, mass spectrometry and protein kinase
      assays. All results indicate that plant PII is not regulated by phosphorylation.
      Edman sequencing of immunoprecipitated A. thaliana PII revealed the N-terminal
      sequences AQISSD and QISSDY, indicating that the mature protein is cleaved from
      its transit peptide in vivo at the site(s) predicted by ChloroP. Western blot
      analysis also demonstrated that plant PII protein expression varies little with
      nutrient regime.

PMID- 15158723
TI  - Secretion of active xylanase C from Streptomyces lividans is exclusively mediated
      by the Tat protein export system.
AB  - The bacterial twin-arginine translocation (Tat) pathway transports folded
      proteins across the cytoplasmic membrane. The precursors targeted to the Tat
      pathway have signal peptides bearing the consensus motif (S/T-R-R-X-F-L-K). The
      xylanase C (XlnC) of Streptomyces lividans is a 20-kDa secreted enzyme. The XlnC
      signal peptide is 49 amino acids long and contains the S-R-R-G-F-L-G sequence,
      which is similar to the twin-arginine consensus motif. In S. lividans, XlnC
      secretion was impaired in a tatC insertion mutant, which is unable to secrete
      proteins that are dependent on the Tat system. When the signal peptide of XlnC
      was replaced by the Sec-dependent signal peptide of xylanase A, XlnC was secreted
      as an inactive form and demonstrated rapid proteolytic degradation in the culture
      supernatant, thus indicating that XlnC was specifically secreted through the Tat
      system. Deletions of the n-region of the XlnC signal sequence showed that a
      minimum of six amino acids residues preceding the twin-arginine motif was
      required to secrete XlnC. Replacement of one or both arginines by lysine residues
      in the twin arginine motif decreased four- and sevenfold, respectively, the
      enzyme production but did not abolish it. However, pulse chase experiments showed
      that the half-life of the precursor was from 2 to 3 h instead of 11 min for the
      wild- type precursor. Since XlnC is not associated with cofactors to exhibit
      activity, it is therefore a newly identified prokaryotic non-redox Tat substrate.

PMID- 15158724
TI  - Mapping of functional sites on the primary structure of the contractile tail
      sheath protein of bacteriophage T4 by mutation analysis.
AB  - In order to determine the functional roles of amino acid residues in gp18 (gp:
      gene product), the contractile tail sheath protein of bacteriophage T4, the
      mutation sites and amino acid replacements of available and newly created
      missense mutants with distinct phenotypes were determined. Amber mutants were
      also utilized for amino acid insertion by host amber suppressor cell strains. It
      was found that mutants that gave rise to a particular phenotype were mapped in a
      particular region along the polypeptide chain. Namely, all amino acid
      replacements in the cold-sensitive mutants (cs, which grows at 37 degrees C, but
      not at 25 degrees C) and the heat-sensitive mutant (hs, lose viability by
      incubation at 55 degrees C for 30 min) except for one hs mutant were mapped in a
      limited region in the C-terminal domain. On the other hand, all the temperature
      sensitive mutants (ts, grow at 30 degrees C, but not at 42 degrees C) and
      carbowax mutants (CBW, can adsorb to the host bacterium in the presence of high
      concentrations of polyethylene glycol, where wild-type phage cannot) were mapped
      in the N-terminal protease-resistant domain, except for one ts mutant. The
      results suggested that the C-terminal region of gp18 is important for contraction
      and assembly, whereas the N-terminal protease-resistant domain constitutes the
      protruding part of the tail sheath.

PMID- 15158725
TI  - Effects of mutagenesis of residue 221 on the properties of bacterial and
      mitochondrial elongation factor EF-Tu.
AB  - During protein biosynthesis, elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA
      (aa-tRNA) to the A-site of ribosomes. This factor is highly conserved throughout
      evolution. However, several key residues differ between bacterial and mammalian
      mitochondrial EF-Tu (EF-Tu(mt)). One such residue is Ser221 (Escherichia coli
      numbering). This residue is conserved as a Ser or Thr in the bacterial factors
      but is present as Pro269 in EF-Tu(mt). Pro269 reorients the loop containing this
      residue and shifts the adjoining beta-strand in EF-Tu(mt) compared to that of E.
      coli EF-Tu potentially altering the binding pocket for the acceptor stem of the
      aa-tRNA. Pro269 was mutated to a serine residue (P269S) in EF-Tu(mt). For
      comparison, the complementary mutation was created at Ser221 in E. coli EF-Tu
      (S221P). The E. coli EF-Tu S221P variant is poorly expressed in E. coli and the
      majority of the molecules fail to fold into an active conformation. In contrast,
      EF-Tu(mt) P269S is expressed to a high level in E. coli. When corrected for the
      percentage of active molecules, both variants function as effectively as their
      respective wild-type factors in ternary complex formation using E. coli Phe
      tRNA(Phe) and Cys-tRNA(Cys). They are also active in A-site binding and in vitro
      translation assays with E. coli Phe-tRNA(Phe). In addition, both variants are as
      active as their respective wild-type factors in ternary complex formation, A-site
      binding and in vitro translation assays using mitochondrial Phe-tRNA(Phe).

PMID- 15158727
TI  - Molten globule-like folding intermediate of asialofetuin at acidic pH.
AB  - In our earlier communication on acid-induced unfolding of bovine serum fetuin
      (BSF), we showed the existence of a molten globule (MG)-like state of BSF at pH
      1.8. The MG state was characterized by higher content of secondary structure than
      native and almost complete loss of tertiary structure and more solvent exposed
      hydrophobic surface [Biochim. Biophys. Acta 1649 (2003) 164]. In this work we
      have shown the presence of an MG-like partially folded intermediate of
      asialofetuin at around pH 1.8, which is much different from the MG state observed
      in BSF in secondary structure contents. The results show that asialofetuin at pH
      1.8 retains approximately 45% secondary structure, as evident from far-UV CD
      spectra. The near-UV CD spectra showed almost complete loss of tertiary
      structure. The intrinsic fluorescence and acrylamide quenching of the lone
      tryptophan residue showed that in acid-induced state, it is buried in the
      interior in a nonpolar environment. The temperature dependence of far-UV CD
      signal of asialofetuin at pH 1.8 exhibits a weak cooperative thermal transition.
      A significant increase in ANS fluorescence showed extensive solvent exposure of
      nonpolar cluster. Size exclusion chromatography (SEC) indicates a slight increase
      in the hydrodynamic size of acid-induced protein. These results suggest that
      asialofetuin at pH 1.8 represents the MG-like folding intermediate. Moreover, our
      results showed that glycosylation might play a role in stabilization of secondary
      structure during acid and/or thermal denaturation.

PMID- 15158726
TI  - Behavior of caldesmon upon interaction of thin filaments with myosin subfragment
      1 in ghost fibers.
AB  - Caldesmon is a component of smooth muscle thin filaments which inhibits their
      interaction with myosin. We have used polarized fluorescence technique to study
      the behavior of caldesmon during the interaction of myosin subfragment 1 (S1)
      with thin filaments reconstituted in rabbit skeletal muscle ghost fibers by
      incorporation of smooth muscle tropomyosin and caldesmon labeled with acrylodan
      at cysteine residue located in the C-terminal region. Significant changes in
      acrylodan fluorescence intensity upon addition of skeletal muscle S1 reflected
      substantial displacement of caldesmon from thin filaments, while alterations in
      the calculated fluorescence parameters indicated the simultaneous rearrangement
      of the remaining caldesmon fraction. The orientation of caldesmon in the S1-thin
      filament complex relative to the fiber axis changes by approximately 7 degrees
      and the mobility of the fluorescent probe by about 9%. The alterations in
      caldesmon orientation were proportional to the strength of S1 binding and
      diminished respectively upon addition of ADP and ADP-V(i). The changes in
      orientation of acrylodan-caldesmon evoked by the interaction of S1 with thin
      filaments were more pronounced than that in AEDANS-F-actin which suggests that
      the spatial arrangement of caldesmon in the complex is governed not only by F
      actin but also by S1. The results may indicate that the changes in spatial
      arrangement of caldesmon are adjusted to the conformation of F-actin and S1
      characteristic for particular steps of the ATP hydrolysis cycle.

PMID- 15158728
TI  - Inhibitory effect of ATP analogs and actin on the modification of myosin
      subfragment 1 with 9-anthroylnitrile.
AB  - The fluorescent probe, 9-anthroylnitrile (ANN), can selectively attach to Ser-180
      at the ATP-binding site of subfragment 1 (S1) of skeletal muscle myosin [J. Biol.
      Chem. 278 (2003) 31891]. We have found that MgATP, MgATPgammaS, MgADP.AlF(4) or
      MgPP(i), but not MgADP, inhibit the incorporation of ANN into S1. The inhibitory
      effect of the nucleotide gamma-phosphate group (or its analog) on the
      modification of S1 with ANN can be explained by the contribution of Ser-180 to
      the binding of the nucleotide gamma-phosphate at the active site of S1. We have
      also observed that the incorporation of ANN into S1.MgADP complex is inhibited by
      actin. These experimental data strongly support the existence of nucleotide
      promoted conformational changes revealed by crystal structures of S1 complexes
      with various nucleotide analogs. They also convincingly show an effect of actin
      on the environment of Ser-180 at the nucleotide binding site of S1.

PMID- 15158729
TI  - Stability of the allergenic soybean Kunitz trypsin inhibitor.
AB  - The soybean Kunitz trypsin inhibitor (SKTI) is a 21.5 kDa allergenic protein that
      belongs to the family of all antiparallel beta-sheet proteins that are highly
      resistant to thermal and chemical denaturation. Spectroscopic and biochemical
      techniques such as circular dichroism (CD), ANS fluorescence and proteolysis were
      used to study its molecular structure under denaturing conditions such as acid
      and heat to which these allergens are commonly exposed during food processing.
      Reduction of native SKTI leads to its complete and rapid proteolysis by pepsin in
      simulated gastric fluid (SGF). Limited proteolysis with chymotrypsin during
      renaturation after heating showed that the native structure reforms at around 60
      degrees C reversing the denaturation. CD spectra revealed that under acid
      denaturing conditions, SKTI shows major changes in conformation, indicating the
      possibility of a molten structure. The existence of this intermediate was
      established by ANS fluorescence studies at different concentrations of HCl. The
      remarkable stability of SKTI to both thermal and acid denaturation may be
      important for its role as a food allergen.

PMID- 15158730
TI  - Inhibition of E. coli CTP synthase by the "positive" allosteric effector GTP.
AB  - Cytidine 5'-triphosphate (CTP) synthase catalyzes the ATP-dependent formation of
      CTP from UTP using either ammonia or l-glutamine as the source of nitrogen. When
      glutamine is the substrate, GTP is required as a positive allosteric effector to
      promote catalysis of glutamine hydrolysis. We show that at concentrations
      exceeding approximately 0.15 mM, GTP actually behaves as a negative allosteric
      effector of E. coli CTP synthase, inhibiting glutamine-dependent CTP formation.
      In addition, GTP inhibits NH(3)-dependent CTP formation in a concentration
      dependent manner. However, GTP does not inhibit the enzyme's intrinsic
      glutaminase activity. Although the activation of CTP synthase by GTP does not
      display cooperative behavior, inhibition of both CTP synthase-catalyzed ammonia-
      and glutamine-dependent CTP synthesis by GTP do exhibit positive cooperativity.
      These results suggest that GTP binding affects CTP synthase catalysis in two
      ways: it activates enzyme-catalyzed glutamine hydrolysis and it inhibits the
      utilization of NH(3) as a substrate by the synthase domain.

PMID- 15158731
TI  - Identification and structural analysis of the antimicrobial domain in hipposin, a
      51-mer antimicrobial peptide isolated from Atlantic halibut.
AB  - Hipposin is a potent 51-mer antimicrobial peptide (AMP) from Atlantic halibut
      with sequence similarity to parasin (19-mer catfish AMP), buforin I (39-mer toad
      AMP), and buforin II (an active 21-mer fragment of buforin I), suggesting that
      the antimicrobial activity of these peptides might all be due to a common
      antimicrobial sequence motif. In order to identify the putative sequence motif,
      the antimicrobial activity of hipposin fragments against 20 different bacteria
      was compared to the activity of hipposin, parasin and buforin II. Neither parasin
      nor the 19-mer parasin-like fragment HIP(1-19) (differs from parasin in only
      three residues) that is derived from the N-terminal part (residues 1-19) of
      hipposin had marked antimicrobial activity. In contrast, the fragment HIP(16-36)
      (identical to buforin II) that is derived from the middle part of hipposin
      (residues 16-36) had such activity, indicating that this part of hipposin
      contained an antimicrobial sequence motif. The activity was enhanced when the
      parasin-like N-terminal sequence was also present, as the fragment HIP(1-36)
      which consists of residues 1-36 in hipposin was more potent than HIP(16-36).
      Extending HIP(1-36) with three C-terminal residues-thereby constructing the
      buforin I-like peptide HIP(1-39) (differs from buforin I in only three residues)
      increased the activity further. Also, the presence of the C-terminal part of
      hipposin (residues 40-51) increased the activity, as hipposin was clearly the
      most potent of all the peptides that were tested. Circular dichroism structural
      analysis of the peptides revealed that they were all non-structured in aqueous
      solution. However, trifluoroethanol and the membrane-mimicking entities
      dodecylphosphocholine micelles and negatively charged liposomes induced
      (amphiphilic) alpha-helical structuring in hipposin. Judging from the structuring
      of the individual fragments, the tendency for alpha-helical structuring appeared
      to be greater in the C-terminal and the buforin II-like middle region of hipposin
      than in the parasin-like N-terminal region.

PMID- 15158732
TI  - Temperature-induced structural changes in putidaredoxin: a circular dichroism and
      UV-VIS absorption study.
AB  - Putidaredoxin (Pdx) is an 11,400-Da iron-sulfur protein that sequentially
      transfers two electrons to the cytochrome P450cam during the enzymatic cycle of
      the stereospecific camphor hydroxylation. We report two transitions in the Pdx UV
      VIS absorption and circular dichroism (CD) temperature dependencies, occurring at
      16.3+/-0.5 degrees C and 28.4+/-0.5 degrees C. The 16.3 degrees C transition is
      attributed to the disruption of the hydrogen bonding of the active center
      bridging sulfur atom with cysteine 45 and alanine 46. The transition at 28.4
      degrees C occurs exclusively in the Pdx(ox) at very nearly the same temperature
      as the earlier reported biphasicity in the redox potential. The formal potential
      temperature slope constancy reflects the relative stability of the concentration
      ratio of both oxidation states. The lower temperature transition affects both
      Pdx(red) and Pdx(ox) to a comparable extent, and their concentration ratio
      remains constant. In contrast, the 28.4 degrees C transition preferentially
      destabilizes Pdx(ox) thereby accelerating the formal potential negative shift and
      lower redox reaction entropy. There is evidence to suggest that disrupting
      hydrogen bonding of the iron ligating cysteines 45, 39 with residues threonine
      47, serine 44, glycine 41, and serine 42 causes the 28.4 degrees C transition.
      The sensitivity of the UV-VIS absorption and CD spectroscopy to subtle structural
      protein backbone transitions is demonstrated.

PMID- 15158733
TI  - Differential substrate behaviour of phenol and aniline derivatives during
      oxidation by horseradish peroxidase: kinetic evidence for a two-step mechanism.
AB  - The catalytic constant (k(cat)) and the second-order association constant of
      compound II with reducing substrate (k(5)) of horseradish peroxidase C (HRPC)
      acting on phenols and anilines have been determined from studies of the steady
      state reaction velocities (V(0) vs. [S(0)]). Since k(cat)=k(2)k(6)/k(2)+k(6), and
      k(2) (the first-order rate constant for heterolytic cleavage of the oxygen-oxygen
      bond of hydrogen peroxide during compound I formation) is known, it has been
      possible to calculate the first-order rate constant for the transformation of
      each phenol or aniline by HRPC compound II (k(6)). The values of k(6) are
      quantitatively correlated to the sigma values (Hammett equation) and can be
      rationalized by an aromatic substrate oxidation mechanism in which the substrate
      donates an electron to the oxyferryl group in HRPC compound II, accompanied by
      two proton additions to the ferryl oxygen atom, one from the substrate and the
      other the protein or solvent. k(6) is also quantitatively correlated to the
      experimentally determined (13)C-NMR chemical shifts (delta(1)) and the calculated
      ionization potentials, E (HOMO), of the substrates. Similar dependencies were
      observed for k(cat) and k(5). From the kinetic analysis, the absolute values of
      the Michaelis constants for hydrogen peroxide and the reducing substrates
      (K(M)(H(2)O(2)) and K(M)(S)), respectively, were obtained.

PMID- 15158734
TI  - Identification and characterization of NuhA, a novel Nudix hydrolase specific for
      ADP-ribose in the cyanobacterium Synechococcus sp. PCC 7002.
AB  - We cloned the gene for a novel Nudix hydrolase in the cyanobacterium
      Synechococcus sp. PCC 7002 and termed it nuhA. The deduced amino acid sequence of
      NuhA included the Nudix motif, GX(5)EX(7)RELXEEXGV, which is common to Nudix
      hydrolases, and in addition, a proline at the 15th amino acid from the C-terminus
      of the Nudix motif, which is characteristic of the subfamily of ADP-ribose
      pyrophosphatases. The recombinant NuhA with a hexahistidine tag was overexpressed
      in Escherichia coli and purified. The recombinant NuhA hydrolyzed ADP-ribose
      specifically among various nucleoside diphosphate derivatives. The hydrolytic
      activity for ADP-ribose required Mg(2+) and was optimal at pH 9.5. The V(max) and
      K(m) values of hydrolysis were 23.6 units mg(-1) and 0.094 mM, respectively. NuhA
      contained an uncharacterized domain in the C-terminal region, termed Pfam-B-3116,
      which is conserved in several hypothetical proteins. The mutated NuhA deficient
      in the Pfam-B-3116 domain failed to form the hexamers that are characteristic of
      NuhA, and exhibited a significantly higher K(m) value for ADP-ribose, suggesting
      that the Pfam-B-3116 domain might be responsible for oligomerization of NuhA and
      full binding affinity for ADP-ribose. These unique features suggest that NuhA is
      a novel type of ADP-ribose pyrophosphatase.

PMID- 15158735
TI  - In situ FTIR ATR spectroscopic study of the interaction of immobilized human
      tumor necrosis factor-alpha with a monoclonal antibody in aqueous environment.
AB  - By in situ FTIR ATR measurements, the antibody (AB) recognition of human tumor
      necrosis factor-alpha (TNFalpha) immobilized on the Ge surface of a multiple
      internal reflection element (MIRE) was investigated. The experiments were
      performed in aqueous environment in a flow-through cell. After immobilization of
      TNFalpha on the Ge-MIRE by direct adsorption from aqueous solution, the
      immobilisate reached stability after about 1 h under flow-through conditions. The
      remaining sites of the Ge surface were saturated by bovine serum albumin (BSA) in
      order to prevent unspecific binding of anti-TNFalpha AB which was then added. The
      obtained FTIR ATR spectra were shown to result exclusively from AB specifically
      interacting with TNFalpha, since the absence of immunoglobulin binding to BSA
      adsorbed to the Ge MIRE was verified by a reference experiment. Finally, the
      stability of all adsorbed protein immobilisates was monitored under flow-through
      conditions for 10.5 h. The TNFalpha-AB complex showed a decrease of 7.4%, whereas
      the BSA adsorbate remained stable. IR measurements were performed with polarized
      light in order to study orientational effects of the immobilized proteins. The
      dichroic ratios and surface concentrations of all used proteins are available
      after quantitative analysis of the amide II bands.

PMID- 15158736
TI  - Proteomic analysis of rat atrial secretory granules: a platform for testable
      hypotheses.
AB  - The recent development of powerful proteomic tools has enabled investigators to
      directly examine the population of proteins present in defined biological
      systems. We report here the first proteomic analysis of atrial secretory
      granules. Approximately 100 distinct protein components of the atrial secretory
      granule proteome were detected using subcellular fractionation and one
      dimensional SDS-PAGE in conjunction with peptide mass fingerprinting by MALDI-TOF
      mass spectrometry. Of this number, 61 proteins were clearly identified by high
      probability data matches and repeated observation. The majority of the proteome
      was found to be membrane-associated with the most prominent proteins being
      peptidylglycine alpha-amidating monooxygenase (PAM) and pro-atrial natriuretic
      peptide (pro-ANP). This proteomic analysis of the rat atrium secretory granule
      produced an assembly of proteins with a diverse array of reported functions. The
      identified proteins fall into seven functional categories: (1) granular
      transport, docking and fusion; (2) signal transduction; (3) calcium
      binding/calcium-dependent; (4) cellular architecture/chaperoning; (5)
      peptide/protein processing; (6) hormone; (7) proton transport. The novel finding
      of several protein processing enzymes and signal transduction proteins offer new
      perspectives on how pro-ANP is stored and processed to ANP during release.
      Accordingly, defining the proteome of the atrial secretory granule provides a
      framework for the development of new hypotheses that address key mechanisms
      governing granule function and ANP secretion.

PMID- 15158737
TI  - Biochemical characterization and crystallization of recombinant 3
      phosphoglycerate kinase of Plasmodium falciparum.
AB  - Human malaria parasite Plasmodium falciparum depends largely on glycolytic
      pathway for energy metabolism during the intraerythrocytic life stage. Therefore,
      enzymes of the glycolytic pathway could offer potential drug targets provided
      novel biochemical and/or structural features of the parasitic enzymes, which
      distinguish them from the host counterpart, could be identified. 3
      Phosphoglycerate kinase (EC 2.7.2.3) catalyzes an important phosphorylation step
      leading to the production of ATP in the glycolytic pathway. We have expressed
      recombinant 3-phosphoglycerate kinase of P. falciparum in Escherichia coli. The
      recombinant protein purified from the soluble fraction of E. coli is
      enzymatically active. The apparent K(m) values determined for adenosine
      triphosphate (ATP) and 3-phosphoglycerate (3-PGA) are 0.63 and 0.52 mM,
      respectively. The enzyme activity was temperature-sensitive. Suramin was found to
      inhibit the recombinant enzyme with an IC(50) value of 7 microM. We have
      crystallized the enzyme form in hexagonal space group P6(1)22 (or its
      enantiomorphic space group) with unit cell parameters a=b=130.7, c=263.9 A.
      Native data have been collected at 3.0-A resolution.

PMID- 15158738
TI  - Crystallization and preliminary X-ray diffraction analysis of an acidic
      phospholipase A(2) complexed with p-bromophenacyl bromide and alpha-tocopherol
      inhibitors at 1.9- and 1.45-A resolution.
AB  - An acidic phospholipase A(2) (PLA(2)) isolated from Bothrops jararacussu snake
      venom was crystallized with two inhibitors: alpha-tocopherol (vitamin E) and p
      bromophenacyl bromide (BPB). The crystals diffracted at 1.45- and 1.85-A
      resolution, respectively, for the complexes with alpha-tocopherol and p
      bromophenacyl bromide. The crystals are not isomorphous with those of the native
      protein, suggesting the inhibitors binding was successful and changes in the
      quaternary structure may have occurred.

PMID- 15158739
TI  - Crystallization and preliminary X-ray crystallographic study of the leech
      protease inhibitor guamerin and its complex with bovine pancreatic chymotrypsin.
AB  - Guamerin, a small peptide inhibitor of the serine protease from Hirudo nipponia,
      was expressed in yeast and crystallized using the vapor diffusion method, with
      MPD as precipitant. The crystal was found to belong to the monoclinic P2(1) space
      group with unit cell parameters a=136.06, b=206.59, c=227.39 A, beta=105.03
      degrees. The guamerin/bovine pancreatic chymotrypsin complex was also
      crystallized using PEG 8K as precipitant. The space group was identified as
      P2(1)2(1)2(1) with unit cell parameters of a=44.01, b=44.30, c=122.47 A. The
      diffraction data of the complex were collected up to a resolution of 2.4 A using
      a synchrotron-radiation source under cryogenic condition.

PMID- 15158740
TI  - Laboratory testing in autoimmune rheumatic diseases.
AB  - There are a number of pathological conditions in which tissue damage occurs in
      association with immune activation directed against components of normal tissue.
      The initial damaging events usually involve cells of the immune system, the T
      cells, but the cell damage releases antigens that become targets for an antibody
      response. The detection and quantification of autoantibodies has become an
      important component in the diagnosis and management of autoimmune rheumatic
      diseases such as rheumatoid arthritis, systemic lupus erythematosus, the systemic
      vasculitides and systemic sclerosis. Each of these diseases is associated with a
      particular autoantibody or group of autoantibodies. They are usually detected by
      their reaction against tissue components using subjective methods such as
      indirect immunofluorescence. Any positive samples are further analysed using more
      specific and quantitative methods for the 'quantification' of the specific
      autoantibody concentration. It is important that these autoantibodies are not
      considered to be 'gold standard' tests: they are no more than markers of the
      disease with significant limitations. They are best used as part of a diagnostic
      panel rather than as a marker indicating one particular disease. Techniques are
      gradually improving, giving numerical results rather than titres, but a lack of
      standardization makes these results extremely variable. Many of the markers show
      no correlation with disease activity. Their use should be restricted to the
      initial investigation and not repeated every time the patient is followed up.
      Other markers do, however, correlate with disease activity and can be used to
      monitor disease. When investigating patients who have symptoms associated with
      autoimmune rheumatic diseases, analytes such as immunoglobulins, complement
      components and C-reactive protein may all be measured.

PMID- 15158741
TI  - Scleroderma--clinical and pathological advances.
AB  - The spectrum of scleroderma spans Raynaud's phenomenon, localized forms of skin
      fibrosis and the clinically most important forms of systemic sclerosis that
      involve inflammatory, vascular and fibrotic pathology. A closer relationship
      between these disparate conditions is now appreciated, and skin sclerosis is no
      longer regarded as mandatory for the diagnosis of systemic sclerosis. There have
      been recent and substantial changes in disease classification, the appreciation
      of its natural history and the investigation and treatment of organ-based
      complications. Although scleroderma still has a high case-specific mortality,
      there have been major improvements in the management of renal and pulmonary
      disease, and areas such as gastrointestinal tract involvement can also often be
      improved. Each of these areas is reviewed, and progress in understanding
      pathogenesis also described. The management of organ-based complications has
      benefited from advances in other branches of medicine. Angiotensin-converting
      enzyme inhibitors for scleroderma renal crisis, proton pump inhibitors for reflux
      oesophagitis and advanced therapies for classes III and IV pulmonary arterial
      hypertension exemplify progress in the treatment of systemic sclerosis. There is
      also the prospect of targeted, cytokine-directed treatments that may for the
      first time offer the prospect of genuine disease-modifying intervention in early
      stage disease. In parallel with these developments, there has been substantial
      progress in disease assessment with the construction and initial validation of
      tools to assess skin biomechanics, functional impairment and the severity and
      activity of systemic sclerosis. It is likely that clinical trials performed over
      the next few years will transform the management of systemic sclerosis and help
      to dispel its reputation as one of the least treatable of the autoimmune
      rheumatic diseases.

PMID- 15158742
TI  - Behcet's disease.
AB  - Behcet's disease is a systemic vasculitis characterized by recurrent oral and
      genital ulcers, and ocular inflammation, and which may involve the joints, skin,
      central nervous system and gastrointestinal tract. It is most common in those of
      Mediterranean and Eastern origin, although it also affects Caucasians. The
      aetiology of the disease remains unknown, but the most widely held hypothesis of
      disease pathogenesis is that of a profound inflammatory response triggered by an
      infectious agent in a genetically susceptible host. Supporting this is the
      consistent association of disease susceptibility with polymorphisms in the human
      leukocyte antigen complex, particularly HLA-B*51. The diagnosis is a clinical
      one, and although there is no single laboratory test specific for the diagnosis
      of Behcet's disease, the 1990 classification criteria perform well in a clinical
      context. Whereas many favoured treatments for single or multisystem disease still
      lack a sound evidential base, cyclosporin and azathioprine perform well in
      clinical trials, and evidence is accumulating for the efficacy of anti-tumour
      necrosis factor therapy in particular clinical situations. This review will focus
      on recent developments in the understanding of disease pathogenesis and clinical
      diagnosis, and review the evidence base for both established and new agents in
      the therapeutic strategy.

PMID- 15158743
TI  - Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disease characterized by inflammation of the
      exocrine glands, leading to impaired function. Here, I review the relatively
      short history of the syndrome and explain why it is frequently underdiagnosed,
      undertreated and under-researched. Attempts to provide classification criteria
      have culminated in the revised American-European Consensus Criteria, which
      provide a sound basis for both clinical management and research. The recognition
      that Sjogren's syndrome is a disease of considerable morbidity has led to a more
      aggressive approach to therapy ranging from topical therapies to systemic
      treatment with secretagogues such as pilocarpine and cemiveline, and
      immunomodulatory drugs such as hydroxychloroquine and interferon-alpha. The
      central role of the glandular epithelial cell is identified as the key to
      understanding the pathogenesis of the disease. Hypofunction rather than
      destruction of these cells is now regarded as the main mechanism of secretory
      failure in Sjogren's syndrome.

PMID- 15158744
TI  - Adult inflammatory myopathies.
AB  - The major inflammatory myopathies of adults-dermatomyositis, polymyositis and
      inclusion body myositis-are uncommon and can be difficult to distinguish from
      many conditions that mimic them clinically. They have a high morbidity; they are
      not infrequently the first sign of an associated malignancy; and they may be a
      part of another connective tissue disease. Their pathogenetic features suggest
      that they are different illnesses. Dermatomyositis and polymyositis are clearly
      inflammatory, both clinically and histologically, and both generally respond to
      therapy directed towards inflammation. Inclusion body myositis is now generally
      recognized as the most common myopathy presenting in patients over the age of 50
      years, and it responds only modestly and sometimes not at all to
      immunosuppressive therapy. In this review, we have summarised the major newly
      recognized features of pathogenesis, the involvement of extramuscular organs, the
      differential diagnosis, diagnostic approaches and the main lines of therapy.

PMID- 15158745
TI  - Paediatric idiopathic inflammatory muscle disease.
AB  - The paediatric idiopathic inflammatory myopathies (IIMs) are a group of rare but
      serious systemic autoimmune conditions of childhood. The most common of the
      paediatric IIMs is juvenile dermatomyositis (JDM), while polymyositis and
      inclusion body myositis are rare in children. JDM has a significantly different
      spectrum of disease from adult dermatomyositis. Juvenile myositis can also occur
      as part of other systemic autoimmune diseases such as scleroderma and systemic
      lupus erythematosus. There has recently been significant progress towards the
      development and validation of tools to measure disease activity and damage in the
      paediatric IIMs. In addition, several new therapeutic avenues have been used to
      treat JDM. This review will discuss developments in the diagnostic criteria for
      JDM, the clinical types and course of these conditions, recent progress in
      disease assessment, treatment options and new developments in research into the
      pathogenesis of paediatric IIM.

PMID- 15158746
TI  - Pregnancy and autoimmune diseases.
AB  - Until about 15 years ago, the general advice to women with autoimmune rheumatic
      diseases, especially systemic lupus erythematosus, systemic sclerosis and
      vasculitic syndromes, was to avoid pregnancy as there was a high risk of maternal
      and fetal morbidity and mortality. However, it is now clear that these risks can
      be reduced in general by avoiding pregnancy when the diseases are active and
      continuing appropriate medication to reduce the chances of disease flare during
      pregnancy. This article will review the evidence for this advice and will also
      consider other issues that should be discussed with women before they attempt to
      become pregnant. This will include the influence of pregnancy on the individual
      autoimmune diseases, as well as the potential impact of the diseases and drug
      therapy on fertility and pregnancy outcomes. Anti-phospholipid antibody syndrome
      has emerged as a major cause of fetal loss, pre-eclampsia and premature birth.
      The clinical and laboratory diagnosis of this condition will not be covered, but
      the reader is referred to an excellent recent review. Much of the data on
      pregnancy and autoimmune rheumatic diseases come from retrospective analyses, but
      some prospective studies have been reported over the past 10 years. There have
      been very few meta-analyses or randomized clinical trials.

PMID- 15158747
TI  - Pulmonary manifestations of systemic autoimmune disease.
AB  - Patients with systemic autoimmune disease may present with a number of different
      pulmonary manifestations. In order to recognise, diagnose and manage these
      manifestations, it is necessary to have a working knowledge of the anatomy and
      physiology of the thorax. This chapter will describe the clinical symptoms and
      clinical examination findings in patients who may have underlying pulmonary
      disease. It will describe the investigations that can be used to confirm or
      refute a possible diagnosis and describe approaches to managing these complex
      clinical cases. The importance of multidisciplinary team working using the skills
      of clinicians, radiologists and pathologists will be highlighted. The use of high
      resolution computed tomography scanning of the thorax to help to delineate the
      type of interstitial lung disease will be described and some of the newer
      modalities available for the treatment of pulmonary hypertension introduced. By
      the end of the chapter, the reader should understand that patients with a single
      underlying autoimmune disease may present with one or more pulmonary
      manifestations and that different autoimmune diseases may present with similar
      pulmonary manifestations. This heterogeneity poses both diagnostic and treatment
      challenges, and many questions still remain regarding optimal treatment.

PMID- 15158748
TI  - Renal manifestations of systemic autoimmune disease: diagnosis and therapy.
AB  - Renal involvement is relatively common in certain systemic autoimmune diseases,
      but can be clinically silent. Active surveillance is, therefore, essential
      because the early recognition of renal involvement may influence the extent of
      renal recovery. Blood pressure control is also essential, regardless of the
      underlying disease. In systemic lupus erythematosus, therapy usually depends on
      the renal biopsy findings as not all forms of renal involvement respond in the
      same way. Typically, for aggressive disease, therapy is with steroids and a
      cytotoxic agent, usually cyclophosphamide initially and then azathioprine. In
      systemic vasculitis with renal involvement, a similar approach is adopted,
      therapy including steroids and cyclophosphamide initially and then steroids and
      azathioprine. With severe fulminant disease, plasma exchange or pulsed
      intravenous methylprednisolone is added initially. Scleroderma renal crises are
      managed by blood pressure control using angiotensin-converting enzyme inhibitors
      and other agents as required. Dialysis and transplantation can be successful in
      these conditions.

PMID- 15158749
TI  - Skin manifestations of systemic autoimmune connective tissue disease: diagnostics
      and therapeutics.
AB  - Skin disease can significantly affect the quality of life of patients suffering
      from rheumatic diseases. In addition, important relationships exist between the
      cutaneous and systemic manifestations of rheumatic disease. It is thus important
      for practicing rheumatologists to have a solid working understanding of the
      subject of rheumatic skin disease. Unfortunately, it is not possible within the
      scope of this chapter to provide a comprehensive overview of the recognition and
      management of all of the cutaneous manifestations of lupus erythematosus (LE),
      much less those of dermatomyositis (DM)/polymyositis and scleroderma/systemic
      sclerosis (SSc) as well. As can be seen in in the text, the cutaneous
      manifestations of polygenic autoimmune disorders such as LE can be as
      heterogeneous clinically as are its systemic manifestations. This discussion will
      therefore focus on recent key developments concerning the diagnosis and
      management of the more common skin changes that the practicing rheumatologist is
      likely to encountered in the three major rheumatic diseases: LE, DM and SSc.

PMID- 15158750
TI  - Direct inhibition of the ubiquitin-proteasome pathway by ester bond-containing
      green tea polyphenols is associated with increased expression of sterol
      regulatory element-binding protein 2 and LDL receptor.
AB  - Green tea has been shown to lower plasma cholesterol, associated with up
      regulation of the low-density lipoprotein receptor (LDLR) although the
      responsible molecular mechanism is unknown. Previously, we reported that ester
      bond-containing green tea polyphenols (GTPs), such as (-)-epigallocatechin-3
      gallate [(-)-EGCG], potently inhibit the tumor cellular proteasome activity,
      which may contribute to the cancer-preventative effect of green tea. In the
      current study, we hypothesize that the proteasome is a heart disease-associated
      molecular target of GTPs. We have shown that ester bond-containing GTPs,
      including (-)-EGCG, potently inhibit the proteasomal activity in intact
      hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cells, as evident by
      accumulation of ubiquitinated proteins and three natural proteasome targets (p27,
      IkappaB-alpha and Bax). (-)-EGCG selectively inhibits the chymotrypsin-like, but
      not trypsin-like, activity of the proteasome. Associated with proteasome
      inhibition by ester bond-containing GTPs, there was a significant, time- and
      concentration-dependent increase in levels of the cleaved, activated, but not the
      precursor, form of sterol regulatory element-binding protein 2 (SREBP-2), an
      essential factor for LDLR transcription. Subsequently, LDL receptor expression
      was increased dramatically in HepG2 and HeLa cells treated with (-)-EGCG. Our
      results suggest that ester bond-containing GTPs inhibit ubiquitin/proteasome
      mediated degradation of the active SREBP-2, resulting in up-regulation of LDLR.
      This identified molecular mechanism may be related to the previously reported
      cholesterol-lowering and heart disease-preventative effects of green tea.

PMID- 15158751
TI  - Permeability behaviour of lipid vesicles prepared from plant plasma membranes-
      impact of compositional changes.
AB  - Exposure of oat seedlings to repeated moderate water deficit stress causes a
      drought acclimation of the seedlings. This acclimation is associated with changes
      in the lipid composition of the plasma membrane of root cells. Here, plasma
      membranes from root cells of acclimated and control plants were isolated using
      the two-phase partitioning method. Membrane vesicles were prepared of total
      lipids extracted from the plasma membranes. In a series of tests the vesicle
      permeability for glucose and for protons were analysed and compared with the
      permeability of model vesicles. Further, the importance of critical components
      for the permeability properties was analysed by modifying the lipid composition
      of the vesicles from acclimated and from control plants. The purpose was to add
      specific lipids to vesicles from acclimated plants to mimic the composition of
      the vesicles from control plants and vice versa. The plasma membrane lipid
      vesicles from acclimated plants had a significantly increased permeability for
      glucose and decreased permeability for protons as compared to control vesicles.
      The results point to the importance of the ratio phosphatidylcholine
      (PC)/phosphatidylethanolamine (PE), the levels of cerebrosides and free sterols
      and the possible interaction of these components for the plasma membrane as a
      permeability barrier.

PMID- 15158752
TI  - Omega-hydroxylation of farnesol by mammalian cytochromes p450.
AB  - Studies have shown that mammalian cytochromes p450 participate in the metabolism
      of terpenes, yet their role in the biotransformation of farnesol, an endogenous
      15-carbon isoprenol, is unknown. In this report, [(14)C]-farnesol was transformed
      to more polar metabolites by NADPH-supplemented mammalian microsomes. In
      experiments with microsomes isolated from acetone-treated animals, the production
      of one polar metabolite was induced, suggesting catalysis by CYP2E1. The
      metabolite was identified as (2E, 6E, 10E)-12-hydroxyfarnesol. In studies with
      purified CYP2E1, 12-hydroxyfarnesol was obtained as the major product of farnesol
      metabolism. Among a series of available human p450 enzymes, only CYP2C19 also
      produced 12-hydroxyfarnesol. However, in individual human microsomes, CYP2E1 was
      calculated to contribute up to 62% toward total 12-hydroxyfarnesol production,
      suggesting CYP2E1 as the major catalyst. Mammalian cells expressing CYP2E1
      demonstrated further farnesol metabolism to alpha,omega-prenyl dicarboxylic
      acids. Since such acids were identified in animal urine, the data suggest that
      CYP2E1 could be an important regulator of farnesol homeostasis in vivo. In
      addition, CYP2E1-dependent 12-hydroxyfarnesol formation was inhibited by
      pharmacological alcohol levels. Given that farnesol is a signaling molecule
      implicated in the regulation of tissue and cell processes, the biological
      activity of ethanol may be mediated in part by interaction with CYP2E1-dependent
      farnesol metabolism.

PMID- 15158753
TI  - Chlorpromazine interaction with phosphatidylserines: a (13)C and (31)P solid
      state NMR study.
AB  - Chlorpromazine (CPZ), a cationic, amphiphilic phenothiazine derivative is widely
      used as an antipsychotic drug because it antagonizes dopaminergic receptors.
      (13)C and (31)P solid-state NMR techniques were employed on phospholipid bilayers
      with and without CPZ. Phosphatidylserine from pig brain (PBPS), 1-palmitoyl-2
      oleoyl phosphatidylserine (POPS), synthetic 1,2-dipalmitoyl phosphatidylcholine
      (DPPC) and chlorpromazineHCl were used to make phospholipid bilayers containing
      two types of phospholipids: DPPC (60%)/PBPS (40%) as well as POPS and PBPS
      bilayers without and with 10% CPZ. CPZ is found to prefer binding to the
      phosphate of phosphatidylserine, but also binding to the carboxyl of the serine
      head group in the DPPC/PBPS/CPZ bilayer is present. (31)P-NMR spectra indicate an
      effect of acyl chain unsaturation on the anisotropic motion of the charged serine
      head group. This implies that the serine head group anisotropic motion is
      restricted by intermolecular rather than intramolecular effects. The degree of
      phospholipid acyl chain unsaturation determines part of the CPZ bilayer
      interaction. The PBPS bilayer has the 22:6 acyl chain at 34 mol% and the
      C(4)?C(5) group of this acyl appears to be a determinant for CPZ bilayer
      interdigitation.

PMID- 15158754
TI  - T3 and Triac inhibit leptin secretion and expression in brown and white rat
      adipocytes.
AB  - Leptin regulates appetite, inhibits food intake, and seems to increase energy
      expenditure. We investigated the effect of triiodothyroacetic acid (Triac), a
      metabolite of T3, which seems to be more thermogenic than T3, on leptin secretion
      and mRNA expression. Rat primary cultures of white and brown adipocytes were
      treated with increasing concentrations of Triac and T3. The effect of different
      types of serum and insulin concentrations was also tested. Serum inhibited leptin
      secretion and mRNA expression. Leptin secretion was also clearly inhibited by
      Triac and T3 in a dose-dependent manner and with similar potency. In the presence
      of norepinephrine (NE), Triac and T3 had a similar inhibitory effect, but the
      inhibition was almost complete in white adipocytes. Parallel results were found
      at the mRNA level, where Triac and T3 had similar inhibitory potency, both alone
      and with NE. We also show that insulin induced dose- and time-dependent increases
      in leptin secretion, reaching maximum levels at 0.5 and 3 nM insulin for white
      and brown adipocytes, respectively. Leptin secretion was higher in white than in
      brown adipocytes. The increases in leptin secretion were preceded by increases in
      leptin mRNA. In conclusion, these data demonstrate for the first time that Triac,
      like T3 and serum, inhibits leptin secretion and expression in white and brown
      adipocytes, whereas insulin has the opposite effect.

PMID- 15158755
TI  - Sphingosine-1-phosphate receptors: receptor specificity versus functional
      redundancy.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that has recently been
      shown to bind cell surface S1P receptors (previously called endothelial
      differentiation gene (Edg) receptors), which are members of the G-protein-coupled
      family of receptors. Signaling via S1P is a complex process, as cells usually
      express a number of these receptors on their surfaces. Many of the S1P receptors
      share common G-proteins, invoking the question of how these receptors are
      specific in their actions. This review describes the coupling pathways of S1P
      receptors, and highlights the in vitro and in vivo evidence for the "uniqueness"
      of each receptor in activating downstream signaling pathways, taking the effect
      of S1P on migration as an example.

PMID- 15158756
TI  - The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (-77G-->A)
      polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and
      hyperlipidemic subjects.
AB  - BACKGROUND: Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in
      cellular cholesterol homeostasis. Two isoforms of ACAT have been reported (ACAT-1
      and ACAT-2). ACAT inhibitors cannot only prevent atherosclerosis formation, but
      may also induce its regression in animals. In humans, an ACAT inhibitor was shown
      to have a lipid-lowering effect. The present study was carried out to clarify the
      relationship between ACAT-1 gene variants and hyperlipidemia. METHODS AND
      RESULTS: To identify genetic variants, we screened 30 subjects with
      hyperlipidemia by direct sequencing. As a result, a missense variant (R526G) and
      a variant in the 5' untranslated region (-77G-->A) were identified. The genotype
      frequencies of each variant were determined in 178 unrelated normolipidemic and
      441 unrelated hyperlipidemic subjects. The alleles frequencies of the R526G
      variant in normolipidemic and hyperlipidemic subjects were 0.676 and 0.633,
      respectively. The alleles frequencies of the -77G-->A variant in normolipidemic
      and hyperlipidemic subjects were 0.503 and 0.515, respectively. Differences in
      allele frequencies between normolipidemic and hyperlipidemic subjects were not
      significant in both variants. R526G variant did not affect plasma concentrations
      of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic
      subjects, plasma concentrations of HDL-C and apoA-I in subjects with -77G-->A
      variant were significantly higher than those in subjects without variant.
      CONCLUSION: Two variants in ACAT-1 gene were identified in subjects with
      hyperlipidemia. -77G-->A variant affects plasma HDL concentrations only in
      hyperlipidemic subjects. These data suggest that the intracellular FC
      concentration might modulate plasma HDL concentrations.

PMID- 15158757
TI  - Evidence of luminal phosphatidylcholine secretion in rat ileum.
AB  - BACKGROUND: Intestinal mucus not only facilitates substrate absorption, but also
      forms a hydrophobic, phosphatidylcholine (PC) enriched, barrier against luminal
      gut contents. METHODS: For evaluation of the origin of PC in intestinal mucus, we
      first analyzed the mucus PC in mice with absent biliary phospholipid secretion
      (mdr2 (-/-) mice) using electrospray ionization (ESI) tandem mass spectroscopy
      (MS/MS). Second, in situ perfused rat jejunum, ileum and colon were analyzed
      after i.v. bolus injections of 155 pmol [(3)H]-PC. Additional in vitro
      experiments were performed with isolated mucosal cells after incubation with the
      PC precursor [(3)H]-choline. RESULTS: In mdr2 (-/-) mice and control animals no
      significant quantitative difference in mucus PC was found, indicating that mucus
      PC is of intestinal and not biliary origin. In situ perfusion studies detected
      intestinal secretion of [(3)H]-PC, which was stimulated in presence of 2 mM
      taurocholate (TC). Secretion rates of [(3)H]-PC were highest in ileum (9.0+/-0.8
      fmol h(-1)xcm(-1)), lower in jejunum (4.3+/-0.5) and minimal in colon (0.8+/
      0.2). It compares to an intestinal secretion of native PC originating to 64% from
      bile, 9% from jejunum, 28% from ileum, and 1% from colon. Complementary in vitro
      studies showed 30-min secretion rates for [(3)H]-PC to be highest in enterocytes
      from ileum (26.5+/-5.3% of intracellular [(3)H]-PC) and jejunum (19.8+/-2.9%),
      and significantly lower in colonocytes (8.4+/-1.3%). CONCLUSION: PC in the
      intestinal mucus originates from secretion by ileal and jejunal enterocytes.

PMID- 15158758
TI  - Rapid exchange of pancreatic lipase between triacylglycerol droplets.
AB  - Two types of experiments were performed to study the reversibility of interfacial
      adsorption of pancreatic lipase (PL) to fat droplets during lipolysis. Lipolysis
      was measured in olive oil/gum arabic emulsions containing radiolabeled triolein
      in the presence of bile salts and lecithin at rate-limiting concentrations of
      porcine PL (PPL) or human PL (HPL). The lipolysis rate in a labeled emulsion,
      i.e. release of [(14)C]oleic acid, was immediately reduced by around 50% upon
      dilution with an equal amount of an unlabeled emulsion. Further, lipolysis was
      rapidly and completely suppressed when a non-exchanging lipase inhibitor was
      present in the second emulsion. These results indicate hopping of lipase between
      emulsion droplets. Alternative explanations were excluded. Hopping of PL between
      triolein droplets stabilized with gum arabic at supramicellar bile salt
      concentrations was observed only in the presence, not in the absence, of
      lecithin. Displacement from a trioctanoin-water interface of active HPL by an
      inactive mutant (S152G) was studied in the presence of bile salts by measuring
      HPL distribution between the water phase and the oil-water interface. Colipase
      was limiting for HPL binding to the oil-water interface (colipase to lipase molar
      ratio: 0.5) and, thus, for lipolysis. Upon adding S152G, which has the same
      affinity for colipase, inactive and active HPL were found to compete for binding
      at the oil-water interface. When equal amounts of HPL and HPL S152G were used,
      the lipolysis rate dropped to half the maximum rate recorded with HPL alone,
      suggesting that half the active HPL was rapidly desorbed from the oil-water
      interface. Therefore, under various conditions, PL does not remain irreversibly
      adsorbed to the oil-water interface, but can exchange rapidly between oil
      droplets, via an equilibrium between soluble and lipid-bound PL.

PMID- 15158759
TI  - Interaction of dietary fat types and sesamin on hepatic fatty acid oxidation in
      rats.
AB  - The interaction of sesamin, one of the most abundant lignans in sesame seed, and
      types of dietary fats affecting hepatic fatty acid oxidation was examined in
      rats. Rats were fed purified experimental diets supplemented with 0% or 0.2%
      sesamin (1:1 mixture of sesamin and episesamin), and containing 8% of either
      palm, safflower or fish oil for 15 days. Among the groups fed sesamin-free diets,
      the activity of various fatty acid oxidation enzymes was higher in rats fed fish
      oil than in those fed palm and safflower oils. Dietary sesamin increased enzyme
      activities in all groups of rats given different fats. The extent of the increase
      depended on dietary fat type, and a diet containing sesamin and fish oil in
      combination appeared to increase many of these parameters synergistically. In
      particular, the peroxisomal palmitoyl-CoA oxidation rate and acyl-CoA oxidase
      activity levels were much higher in rats fed sesamin and fish oil in combination
      than in animals fed sesamin and palm or safflower oil in combination. Analyses of
      mRNA levels revealed that a diet containing sesamin and fish oil increased the
      gene expression of various peroxisomal fatty acid oxidation enzymes and
      PEX11alpha, a peroxisomal membrane protein, in a synergistic manner while it
      increased the gene expression of mitochondrial fatty acid oxidation enzymes and
      microsomal cytochrome P-450 IV A1 in an additive manner. It was concluded that a
      diet containing sesamin and fish oil in combination synergistically increased
      hepatic fatty acid oxidation primarily through up-regulation of the gene
      expression of peroxisomal fatty acid oxidation enzymes.

PMID- 15158760
TI  - Calmodulin antagonist W-7 inhibits de novo synthesis of cholesterol and
      suppresses secretion of de novo synthesized and preformed lipids from cultured
      hepatocytes.
AB  - The effects of a calmodulin antagonist W-7 were studied on the synthesis and
      secretion of lipids in primary rat hepatocytes and McArdle-RH7777 cells. In time
      course experiments, W-7 (20 microM) inhibited secretion of newly synthesized
      triacyl[(3)H]glycerol by 35%. When the cells were pre-treated overnight with W-7
      (20 microM), followed by incubation with [(3)H]oleate, a significant decrease in
      the secretion of triacylglycerol (TG) and cholesteryl ester (CE) was observed. De
      novo synthesis of cholesterol from acetate or mevalonolactone was inhibited by W
      7, but not glycerolipid synthesis from glycerol and oleic acid precursors.
      Concentration-response curves for the effects of overnight pre-incubation with W
      7 followed labeling with [(3)H]glycerol and [(14)C]mevalonolactone revealed that:
      (1). the inhibitory effect of W-7 was concentration-dependent and appeared even
      at the lowest concentration examined (1 microM). W-7 at a concentration of 20
      microM suppressed secretion of TG by 60% (P<or=0.002), phosphatidylcholine (PC)
      by 31% (P<or=0.05), CE by 59% (P<or=0.002) and cholesterol by 64% (P<or=0.002).
      (2). The incorporation of [(14)C]mevalonolactone into cellular cholesterol and CE
      was decreased significantly, while W-7 did not have any significant effect upon
      incorporation of [(3)H]glycerol into glycerolipids, except at the highest
      concentration examined (50 microM), where synthesis of both TG and PC was
      significantly suppressed. (3). While the percentage of secreted de novo
      synthesized glycerolipids and CE decreased proportionally with increasing
      concentration of W-7, the percentage of secreted newly made cholesterol remained
      unaffected at any concentration of W-7. In the absence of W-7, about 19% of newly
      formed cholesterol became esterified into CE, whereas W-7 increased cholesterol
      esterification in a concentration-dependent manner. (4) W-7 (20 microM) also
      suppressed the secretion of preformed cholesterol by 24% and CE by 55% but did
      not affect the recruitment of preformed cholesterol for esterification. About
      6.5% of pre-labeled cholesterol and 20% of CE were directed to secretion, which
      was suppressed in the presence of W-7 by 17% (P<or=0.09) and 48% (P<or=0.001),
      respectively. These results suggest that, W-7 in the range of 1-20 microM
      inhibited de novo synthesis of cholesterol and the secretion of both de novo
      synthesized and preformed lipids.

PMID- 15158761
TI  - Prostaglandin F(2alpha) is protective for apoptosis stimulated synergistically
      with 12-O-tetradecanoyl phorbol-beta-acetate and nordihydroguaiaretic acid in
      Madin-Darby canine kidney cells.
AB  - We recently found that 12-O-tetradecanoyl phorbol-beta-acetate (TPA) induced
      apoptosis in cultured Madin-Darby canine kidney (MDCK) cells. The present study
      shows that the apoptosis was mediated by the activation of caspases including
      caspase-3 and -7. Moreover, nordihydroguaiaretic acid (NDGA), a general
      lipoxygenase (LOX) inhibitor, synergistically stimulated the TPA-induced
      apoptosis despite no activation with NDGA alone. TPA preferentially increased the
      transcription of cyclooxygenase (COX)-2 in MDCK cells, whereas the expression of
      LOXs was almost negligible. These findings suggested that the effect of NDGA was
      independent of the inhibition of LOXs. The study using a cell-permeable 2',7'
      dichlorofluorescin diacetate confirmed the more remarked production of reactive
      oxygen species at 6 h after the cells were treated with a mixture of TPA and
      NDGA. Calcium ionophore A23187 was markedly effective to attenuate the TPA
      induced apoptosis, indicating that elevated endogenous prostaglandins (PGs)
      served as survival factors through not only the activation of phospholipase A(2)
      by A23187 but also the induction of COX-2 by TPA. Consistent with this
      indication, exogenous addition of PGF(2alpha), a predominant prostanoid in MDCK
      cells, was the most potent to protect the cells from the apoptosis induced by a
      mixture of TPA and NDGA.

PMID- 15158762
TI  - Expression of the lysophospholipid receptor family and investigation of
      lysophospholipid-mediated responses in human macrophages.
AB  - Some of the biological effects of lipoproteins have been attributed to their
      association with lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC),
      sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC). These
      lysophospholipids mediate multiple biological responses via several G protein
      coupled receptors (GPR). The expression of these receptors, however, has not been
      systematically investigated in primary human monocytes and macrophages as major
      cells involved in atherosclerosis. The mRNAs for all 15 receptors described so
      far were detected in monocytes, macrophages, foam cells and high density
      lipoprotein (HDL(3))-treated cells using real time RT-PCR. Immunoblots revealed
      that S1P(1), S1P(2), S1P(4), LPA(1), LPA(2) and GPR65 are expressed in monocytes
      and macrophages, while S1P(5) and LPA(3) have not been detected. S1P(3) was
      induced during differentiation but down-regulated by lipid-loading and HDL(3),
      whereas LPA(1) was down-regulated in differentiated macrophages. The influence of
      S1P on macrophages was investigated and the induction of CD32 indicates an
      enhanced phagocytic activity. Altogether, these data give insights into the
      expression and regulation of lysophospholipid receptors in primary human
      monocytes, macrophages and foam cells.

PMID- 15158763
TI  - Detection of conjugated C16 PUFAs in rat tissues as possible partial beta
      oxidation products of naturally occurring conjugated linoleic acid and its
      metabolites.
AB  - In a previous paper, we showed that naturally occurring conjugated linoleic acid
      (CLA) from butter fat is metabolized in vivo to higher metabolites such as
      conjugated diene (CD) 18:3, CD 20:3 and CD 20:4, all the while retaining the
      conjugated diene structure. In this paper, we describe the detection of two more
      metabolites with characteristic conjugated diene UV spectra. HPLC retention
      times, UV and MS spectra identified the CLA metabolites as CD 16:2 and CD 16:3.
      The accumulation of CD 16:2 was significantly higher than that of CD 16:3 in all
      tissues examined. Tissue distributions of CD 16:2 and CD 16:3 were similar, with
      plasma and adipose tissue showing the highest levels, while kidney had the lowest
      and the liver an intermediate level. CD 16 fatty acids accounted for about 20% of
      the total CLA metabolites. The kidney, however, was an exception where CD 16
      fatty acids accounted for only 11% of total metabolites. Analyses of liver lipid
      classes showed that CD 16:2 and CD 16:3 were preferentially incorporated into
      neutral lipids. This preferential incorporation was very similar to CLA as shown
      previously. We hypothesize that CD 16:2 and CD 16:3 may be derived from partial
      beta-oxidation of CLA and CD 20:4, respectively, even though we cannot rule out
      that CD 16:3 may also be derived from CD 18:3 and CD 20:3. Incubation of skin
      human fibroblasts from X-linked adrenoleukodystrophy (ALD) patients with c9,t11
      CLA showed that CD 16:2 formation in ALD cells was about 50% lower than control
      cells. This result may tempt to hypothesize that, at least in part, CD 16:2 is
      beta-oxidized in peroxisomes.

PMID- 15158764
TI  - New cancer therapeutics: target-specific in, cytotoxics out?
AB  - The International Conference on Molecular Targets and Therapeutics, jointly
      sponsored by the American Association for Cancer Research (AACR), National Cancer
      Institute (NCI) and European Organization for Research and Treatment of Cancer
      (EORTC), was held in Boston on November 17-21, 2003. It offered updates of the
      latest developments and emerging trends in anti-cancer research. One of the most
      exciting areas was the development of molecular target-specific therapeutics that
      have the potential to maximize therapeutic benefit while minimizing toxicity to
      normal cells. Signifying the coming of age of tumour-specific targets and agents
      was the recurring theme, to urgently develop and validate biomarker assays as
      surrogate endpoints; both for showing that targeted agents act as expected and
      for providing proof of concept in the scientific rationale of new agents. Given
      the dominance of protein tyrosine kinase inhibitors in small-molecule drug
      design, a strong case was made for the implementation of phospho-proteomics or
      signal transduction signatures and pharmaco-proteomics or chemotherapeutic scans
      in phase I/II trials--or for the future "Nanolab", eloquently described by Leroy
      Hood. However, molecular targeted agents-other than imanitib (Gleevec)--have yet
      to enter broad clinical use and several presentations described efforts for
      improving classical (cytotoxic) chemotherapeutic agents by targeting them
      selectively to tumour cells.

PMID- 15158765
TI  - HIV resistance to the fusion inhibitor enfuvirtide: mechanisms and clinical
      implications.
AB  - The increasing prevalence of HIV isolates resistant to one or multiple
      antiretroviral drugs has fueled the search for new agents that work by novel
      mechanisms. Enfuvirtide (ENF), licensed in 2002, is the first marketed
      antiretroviral (ARV) agent that targets viral entry. ENF blocks the virus
      replication cycle by binding to gp41, a critical component of the machinery used
      by HIV to enter host cells. As with all ARVs, HIV can evolve resistance to ENF.
      However, resistance to ENF appears to be somewhat more complex and can derive
      through either direct or indirect pathways. Direct resistance occurs when
      mutations in the first heptad repeat of gp41, which constitutes the ENF-binding
      site, reduce ENF binding. Indirect resistance is not attributable to changes in
      the ENF-binding site per se, but rather to changes in the HIV envelope
      glycoprotein (gp120) that reduce ENF susceptibility by more complex mechanisms.
      The extensive gp120 amino-acid sequence heterogeneity found in primary viral
      isolates results in unusually broad variability in susceptibility to ENF, and
      indeed to other classes of HIV entry inhibitors. Clinical data reported to date
      do not provide clear evidence that virological outcome of ENF therapy can be
      predicted by either genotypic or phenotypic analysis of viruses present in
      patients at initiation of ENF therapy. Although ENF offers an exciting
      opportunity to treat multi-drug resistant HIV, these observations suggest a
      greater understanding of ENF resistance may be required to ensure the most
      effective use of ENF in infected patients. Many aspects of the complexities
      observed in ENF resistance are likely to be relevant for other classes of HIV
      entry inhibitors currently in development.

PMID- 15158766
TI  - ROS stress in cancer cells and therapeutic implications.
AB  - Reactive oxygen species (ROS) are constantly generated and eliminated in the
      biological system, and play important roles in a variety of normal biochemical
      functions and abnormal pathological processes. Growing evidence suggests that
      cancer cells exhibit increased intrinsic ROS stress, due in part to oncogenic
      stimulation, increased metabolic activity, and mitochondrial malfunction. Since
      the mitochondrial respiratory chain (electron transport complexes) is a major
      source of ROS generation in the cells, the vulnerability of the mitochondrial DNA
      to ROS-mediated damage appears to be a mechanism to amplify ROS stress in cancer
      cells. The escalated ROS generation in cancer cells serves as an endogenous
      source of DNA-damaging agents that promote genetic instability and development of
      drug resistance. Malfunction of mitochondria also alters cellular apoptotic
      response to anticancer agents. Despite the negative impacts of increased ROS in
      cancer cells, it is possible to exploit this biochemical feature and develop
      novel therapeutic strategies to preferentially kill cancer cells through ROS
      mediated mechanisms. This article reviews ROS stress in cancer cells, its
      underlying mechanisms and relationship with mitochondrial malfunction and
      alteration in drug sensitivity, and suggests new therapeutic strategies that take
      advantage of increased ROS in cancer cells to enhance therapeutic activity and
      selectivity.

PMID- 15158767
TI  - Evolution of the serine beta-lactamases: past, present and future.
AB  - We present a protein structure-based phylogeny of Classes A, C and D of the
      serine beta-lactamases, and a new, detailed, sequence-based phylogeny of the
      Class A beta-lactamases. In addition, we discuss the historical evolution of
      Classes C and D. The evolutionary histories of all three classes indicate that
      the serine beta-lactamases are ancient enzymes, originating over two billion
      years ago, and that some have been on plasmids for millions of years. We also
      discuss the recent, antibiotic-era, evolution of the serine beta-lactamases in
      response to the clinical use of beta-lactam antibiotics. We also discuss a method
      that is being used to predict the future evolution of beta-lactamases in response
      to selection with new drugs.

PMID- 15158768
TI  - Anti-vascular tumor therapy: recent advances, pitfalls and clinical perspectives.
AB  - Anti-vascular tumor therapy represents a promising new strategy for cancer
      treatment. Anti-vascular treatment may be divided in anti-angiogenic and vascular
      targeting therapy. Whereas anti-angiogenic drugs aim on the inhibition of new
      vessel formation, vascular targeting compounds are designed to selectively
      destruct preexisting tumor blood vessels leading to secondary tumor cell death.
      Both anti-angiogenic drugs and vascular targeting agents have proven effective
      anti-tumoral activity in numerous preclinical studies over the last decade. In
      vivo, a combination with anti-vascular tumor therapy enhances the effects of
      other treatment modalities as chemo- and radiotherapy. Phase I clinical studies
      revealed a number of well-tolerated candidates. As monotherapy, however, anti
      angiogenic treatment lacked efficacy in randomized clinical studies so far. In
      contrast, combination of anti-angiogenic therapy with chemotherapy was highly
      effective in an encouraging, large randomized phase III trial on metastatic
      colorectal cancer. This review will outline recent advances in the preclinical
      and clinical development of anti-vascular therapy with focus on vascular
      targeting. Conceptual differences between anti-angiogenic and vascular targeting
      therapies will be discussed with emphasis on specific problems and pitfalls in
      the conversion into the clinic.

PMID- 15158769
TI  - Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and
      irradiation: mechanisms and clinical implications.
AB  - Activation of cell surface death receptors by their cognate ligands triggers
      apoptosis. Several human death receptors (Fas, TNF-R1, TRAMP, DR4, DR5, DR6, EDA
      R and NGF-R) have been identified. The most promising cytokine for anticancer
      therapy is TRAIL/APO-2L, which induces apoptosis in cancer cells by binding to
      death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. The cytotoxic activity of TRAIL is
      relatively selective to cancer cells compared to normal cells. Signaling by TRAIL
      and its receptors is tightly regulated process essential for key physiological
      functions in a variety of organs, as well as the maintenance of immune
      homeostasis. Despite early promising results, recent studies have identified
      several TRAIL-resistant cancer cells of various origins. Based on molecular
      analysis of death-receptor signaling pathways several new approaches have been
      developed to increase the efficacy of TRAIL. Resistance of cancer cells to TRAIL
      appears to occur through the modulation of various molecular targets. They may
      include differential expression of death receptors, constitutively active Akt and
      NFkappaB, overexpression of cFLIP and IAPs, mutations in Bax and Bak genes, and
      defects in the release of mitochondrial proteins in resistant cells. Conventional
      chemotherapeutic and chemopreventive drugs, and irradiation can sensitize TRAIL
      resistant cells to undergo apoptosis. Thus, these agents enhance the therapeutic
      potential of TRAIL in TRAIL-sensitive cells and sensitize TRAIL-resistant cells.
      TRAIL and TRAIL-receptor antibodies may prove to be useful for cancer therapy,
      either alone or in association with conventional approaches such as chemotherapy
      or radiation therapy. This review discusses intracellular mechanisms of TRAIL
      resistance and various approaches that can be taken to sensitize TRAIL-resistant
      cancer cells.

PMID- 15158770
TI  - Pathogenicity of pap-negative avian Escherichia coli isolated from septicaemic
      lesions.
AB  - Recent studies by DNA-DNA hybridisation assays conducted on a large collection of
      Escherichia coli strains isolated from chickens, ducks and turkeys suffering from
      colibacillosis, showed that 76% of the strains were negative for the presence of
      the pap gene cluster. The objective of this paper was to study the virulence
      associated with the avian E. coli strains negative for the P fimbriae, but
      carrying the f17 or the afa-8 gene cluster coding for adhesins associated with
      strains pathogenic for mammals. Three strains carrying the f17 fimbriae and three
      carrying the afa-8 adhesin-encoding gene cluster were studied in three in vivo
      experimental models of avian colibacillosis: subcutaneous inoculation of 1-day
      old chicks, inoculation of specific-pathogen-free (SPF) chickens via the intra
      thoracic air sac, and intra-tracheal inoculation of axenic chickens. The results
      showed that the six P-negative E. coli isolates carrying the f17 or the afa-8
      gene cluster were lethal for 1-day-old chicks. They were also able to reproduce
      clinical signs and lesions of colibacillosis (aerosacculitis, pericarditis,
      perihepathitis), with bacteraemia and septicaemia, in SPF chickens inoculated via
      the thoracic air sacs as well as in axenic chickens inoculated by the intra
      tracheal route. Further studies with f17 and afa-8 allelic mutants constructed by
      disruption must be performed to confirm a role of F17 fimbrial and Afa-VIII
      afimbrial adhesins in the pathogenesis of avian colibacillosis.

PMID- 15158771
TI  - Down-regulation of gp63 in Leishmania amazonensis reduces its early development
      in Lutzomyia longipalpis.
AB  - The zinc protease (gp63) of promastigotes was found to play a role in the sand
      fly part of the Leishmania life cycle. Lutzomyia longipalpis females were fed
      with promastigotes (10(6) per ml) of a Leishmania amazonensis clone whose gp63
      was up- and down-regulated by directional cloning into P6.5 for sense- and anti
      sense transcription. Early development was found to differ significantly between
      the sense- and anti-sense transfectants 2 days post-feeding. The sense
      transfectants overexpressing gp63 were found similar to those with the vector
      alone: both developed in the gut at high rates of approximately 90-100% and at a
      high density with moderate to heavy parasite loads in >70% of the infected
      females. In contrast, the anti-sense transfectants with gp63 down-regulated
      developed at a lower rate (approximately 70%) and, significantly, at a very low
      density, with moderate to heavy parasite loads only in approximately 30% of the
      infected females. On day 9 post-feeding, all three groups of transfectants
      developed at a similar rate of approximately 50% with comparable parasite loads.
      Thus, gp63 plays a role at the early stage of L. amazonensis establishment in L.
      longipalpis.

PMID- 15158772
TI  - Protective role of ETA endothelin receptors during the acute phase of Trypanosoma
      cruzi infection in rats.
AB  - Chagas' disease, caused by Trypanosoma cruzi, has an acute phase characterized by
      blood-circulating trypomastigotes and amastigote proliferation in several cell
      types, especially muscle cells. In the chronic phase, around 70% of infected
      people are asymptomatic (latent form). The remainder develop chagasic
      cardiomyopathy and/or digestive syndromes. There is evidence for aggravation of
      the chronic cardiac pathology by endothelin-mediated vasoconstriction. Holtzman
      rats have proven to be a good model for Chagas' disease acute phase and latent
      chronic phase. Now, we investigate the effects of prolonged treatment with an
      endothelin ET(A) receptor antagonist, BSF 461314, during the acute phase on
      parasitemia, coronary flow, tissue parasitism and the inflammatory process. Using
      isolated heart in Langendorff's preparation, endothelial dysfunction was observed
      only in non-treated infected animals. Histoquantitative analyses carried out in
      heart and diaphragm showed higher tissue parasitism and/or inflammatory process
      in BSF 461314-treated animals. Our data indicate that endothelin ET(A) receptors
      contribute to the initial mechanisms of parasite control. Impairment of the
      endothelium-dependent vasodilatation favors hazardous effects. However, blocking
      endothelin ET(A) receptors can prevent the latter.

PMID- 15158773
TI  - A monoclonal antibody to glucosylceramide inhibits the growth of Fonsecaea
      pedrosoi and enhances the antifungal action of mouse macrophages.
AB  - Fungal glucosylceramides (GlcCer) are conserved lipid components in a large
      variety of pathogenic and non-pathogenic fungal species, but their biological
      functions are still unclear. Recent studies demonstrate that GlcCer are
      immunologically active components inducing the production of antifungal
      antibodies. In this work, a major GlcCer was purified and characterized from
      mycelial forms of Fonsecaea pedrosoi, the most frequent causative agent of
      chromoblastomycosis. As determined by fast atom bombardment mass spectrometry
      (FAB-MS) analysis, the purified molecule was identified as the conserved
      structure N-2'-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8
      sphingadienine. A monoclonal antibody (Mab) against this structure was used in
      indirect immunofluorescence with the different morphological stages of F.
      pedrosoi. Only the surface of young dividing cells was recognized by the
      antibody. Treatment of F. pedrosoi conidia with the Mab against GlcCer resulted
      in a clear reduction in fungal growth. In addition, the Mab also enhanced
      phagocytosis and killing of F. pedrosoi by murine cells. These results suggest
      that, in F. pedrosoi, GlcCer seem to be cell wall components targeted by
      antifungal antibodies that directly inhibit fungal development and also enhance
      macrophage function, supporting the use of monoclonal antibodies to GlcCer as
      potential tools in antifungal immunotherapy.

PMID- 15158774
TI  - Safety and efficacy of immune-stimulating complex-based antigen delivery systems
      for neonatal immunisation against respiratory syncytial virus infection.
AB  - To protect against human respiratory syncytial virus (hRSV)-induced bronchiolitis
      in early infancy, vaccines need to be designed which are effective in the
      neonatal period. To test the safety and efficacy of adjuvants in neonatal mice,
      we injected hRSV surface proteins combined with immune-stimulating complexes
      (ISCOMs) prepared from fractions A, C or A + C of Quillaja saponins. All were
      well tolerated in adults, but A + C ISCOMS proved lethal in neonates; A or C
      fractions alone were well tolerated by neonates up to the adult dose. hRSV-ISCOM
      A induced antibody responses similar to combined fractions, and potent in vitro
      cytotoxic T cell responses. Adult-like in vitro cytotoxicity against hRSV
      infected targets and precursor cytotoxic T cell frequencies were observed within
      one week of neonatal priming and hRSV-ISCOM A-primed neonates showed virtually
      complete protection against subsequent viral challenge. hRSV challenge was
      associated with some pulmonary eosinophilia in both age groups, with higher IL-4
      production by lung CD4+ T cells in mice primed as neonates. This was, however,
      accompanied by only minor (approximately 10%) and transient illness and weight
      loss. Thus, the identification of hRSV antigen delivery systems with an age
      appropriate adjuvanticity/reactogenicity balance may be feasible even in the
      vulnerable early-life period.

PMID- 15158775
TI  - Association of adherence and motility in interleukin 8 induction in human
      intestinal epithelial cells by Vibrio cholerae.
AB  - Interleukin 8 (IL-8) mRNA expression in Vibrio cholerae-infected human intestinal
      epithelial cells Int407 was determined by quantitative real-time RT-PCR and
      secretion measured by ELISA. Incubation of Int407 with V. cholerae O395 resulted
      in increased IL-8 mRNA expression as early as within 2 h of infection. Kinetics
      of IL-8 secretion reached a peak at about 8 h (780 pg/ml) and decreased
      thereafter. Induction of IL-8 was significantly high among various toxin
      producing strains of V. cholerae belonging to serovar O1, O139 and non-O1
      compared to non-toxinogenic strains. Induction of IL-8 was maximum in V. cholerae
      O395, required live cells and was dependent on de novo protein synthesis. The
      bacterial culture supernatant and crude cell envelope showed IL-8 stimulating
      activity. Infection of the monolayer with V. cholerae O395 cheY4 null mutant
      (O395YN), defective in adherence and motility, resulted in highly reduced levels
      of IL-8 expression, while hyperadherent and hypermotile mutant (O395Y) with the
      cheY4 gene duplicated also showed very high IL-8 expression. Another
      hyperadherent icmF insertion mutant (O395F) with reduced motility showed almost
      half the amount of IL-8 expression compared to O395Y. These results clearly
      indicate that both motility and adherence to intestinal epithelial cells are
      possible triggering factors contributing to IL-8 mRNA expression by V. cholerae.

PMID- 15158776
TI  - Lipid rafts in lymphocyte activation.
AB  - The existence of sphingolipid- and cholesterol-rich membrane microdomains called
      "lipid rafts", as well as their role in lymphocyte biology, has been widely
      debated during the last few years. Plasma membrane microdomains seem to be
      primarily involved in initiation and propagation of the signal transduction
      cascade associated with lymphocyte activation. In this review, we discuss the
      recent literature suggesting that, during lymphocyte activation and chemotaxis,
      lipid rafts act as platforms to compartmentalise signalling and facilitate
      specific protein-protein interactions.

PMID- 15158777
TI  - Pathogenic consequences of Neisseria gonorrhoeae pilin glycan variation.
AB  - A Neisseria gonorrhoeae (gonococcus, GC) pilin glycosylation gene, pgtA, can
      either possess or lack phase-variation ability. Many GC, particularly the
      disseminated strains, carry a phase-variable pgtA. However, other GC,
      predominantly the uncomplicated gonorrhea isolates, carry a pgtA lacking phase
      variability. These and other results suggest GC pilin glycan's pathogenic
      involvement.

PMID- 15158778
TI  - Regulation of picornavirus gene expression.
AB  - Members of the Picornaviridae are positive- strand RNA viruses that cause a
      variety of human diseases such as poliomyelitis, the common cold, myocarditis,
      and hepatitis. Although the diseases caused by picornaviruses are diverse, the
      genome organization and mechanisms of gene expression are highly conserved among
      family members. This review will discuss the mechanisms of viral gene expression
      including cap-independent translation initiation, host cell translation shut off,
      viral polyprotein processing, and RNA replication.

PMID- 15158779
TI  - The binding of guanine-guanine mismatched DNA to naphthyridine dimer immobilized
      sensor surfaces: kinetic aspects.
AB  - Naphthyridine dimer composed of two naphthyridine chromophores and a linker
      connecting them strongly, and selectively, binds to the guanine-guanine mismatch
      in duplex DNA. The kinetics for the binding of the G-G mismatch to the
      naphthyridine dimer was investigated by surface plasmon resonance assay. The
      sensor surface was prepared by immobilizing naphthyridine dimer through a long
      poly(ethylene oxide) linker with the ligand density of 9.1 x 10(-12) fmolnm(-2).
      The kinetic analyses revealed that the binding of the G-G mismatch was sequence
      dependent on the flanking base pairs, and the G-G mismatches flanking at least
      one G-C base pair bound to the surface via a two-step process with a 1:1 DNA
      ligand stoichiometry. The first association rate constant for the binding of the
      G-G mismatch in the 5'-CGG-3'/3'-GGC-5' sequence to the naphthyridine dimer
      immobilized sensor surface was 3.2 x 10(3)M(-1)s(-1) and the first dissociation
      rate constant was 1.4 x 10(-2)s(-1). The association and dissociation rate
      constants for the second step were insensitive to the flanking sequences, and
      were almost of the same order of magnitude as the first dissociation rate
      constant. This indicates that the second step had only a small energetic
      contribution to the binding. The association constant calculated from kinetic
      parameters was 2.7 x 10(5)M(-1), which is significantly smaller than the apparent
      association constants obtained from experiments in solution. Electrospray
      ionization time-of-flight (ESI-TOF) mass spectrometry on the complex produced
      from the G-G mismatch and naphthyridine dimer showed the formation of the 1:1
      complex and a 1:2 DNA-ligand complex in solution. The latter complex became the
      dominant complex when a six-fold excess of naphthyridine dimer was added to DNA.

PMID- 15158780
TI  - YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory
      activity from Chromobacterium sp. QS3666.
AB  - The structure elucidation and biological activity of novel YM-254890 (1)
      analogues and semi-synthetic derivatives are described. Three natural analogues,
      YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the
      fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated
      derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890.
      Their structures were determined by one- and two-dimensional NMR studies and mass
      spectrometry. Among these compounds, two natural analogues 2-3 which possessed
      acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar
      to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1.
      This indicates that the acyl beta-HyLeu residue plays an important role in
      activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha
      residue is not critical to activity. The other hydrogenated derivative 5 had
      significantly less activity, which could be attributed to conformational
      differences.

PMID- 15158781
TI  - Synthesis and in vitro antimicrobial activities of 2-hydroxy-6-methyl-7
      (arylamino)-1,7-dihydropurin-8-ones.
AB  - A number of 2-hydroxy-6-methyl-7-(arylamino)-1,7-dihydropurin-8-ones have been
      synthesized. 3-Oxo-2-(arylhydrazono)butyric acid ethyl ester were acetylated and
      treated with triethyl amine and formamide in presence of 1,4-dioxane to yield N
      (5-acetyl-4-ethoxy-2-oxo-2,5-dihydro-imidazol-1-yl)-N-arylacetamide, which on
      refluxation with urea and freshly prepared sodium ethoxide yielded the title
      compound. All the newly synthesized compounds have been characterized by
      spectroscopic and elemental analysis data. The synthesized compounds were
      screened against a representative panel of susceptible and resistant Gram
      positive and Gram-negative bacteria using a standard antibiotic drug purinthol as
      control. Quantitative structure-activity relationship has also been interpreted
      in terms of correlation of biological activity with molecular refractive index
      parameters (M(R)) and Hammett substituent constant (sigma).

PMID- 15158782
TI  - Synthesis, conformation, and immunogenicity of monosaccharide-centered
      multivalent HIV-1 gp41 peptides containing the sequence of DP178.
AB  - Several monosaccharide-centered multivalent HIV-1 gp41 peptides containing the
      sequence of DP178 were synthesized. Conformational studies showed that
      multivalent assembly enhanced the alpha-helical content of the peptide.
      Therefore, 2-, 3-, or 4-alpha-helix bundles of peptide DP178 could be obtained by
      assembling the peptide on a suitable bi-, tri-, or tetravalent template.
      Immunization studies indicated that while peptide DP178 alone was poorly
      immunogenic, the tetravalent peptide MVP-1 raised high titers of antibodies in
      mice that recognize not only peptide DP178 but also the native HIV-1 glycoprotein
      gp41, even in the absence of a carrier protein or adjuvant. The study suggests
      that carbohydrate-centered multivalent peptides provide not only a model for
      mimicking protein alpha-helix-bundle structure, but also an effective immunogen
      for raising high-titer antibodies against HIV-1 envelope glycoprotein gp41.

PMID- 15158783
TI  - New class of potent antinociceptive and antiplatelet 10H-phenothiazine-1
      acylhydrazone derivatives.
AB  - In this work, we reported the synthesis and evaluation of the analgesic,
      antiinflammatory, and antiplatelet properties of new phenothiazine-attached
      acylhydrazone derivatives (6), designed exploring the molecular hybridization
      approach between antipsychotic chlorpromazine (4) and other heterocyclic
      derivatives (3) and (5) developed at LASSBio. Target compounds were synthesized
      in very good yields exploiting diphenylamine (7) as starting material, through
      regioselective functionalization of the C-1 position of 10H-phenothiazine ring.
      The evaluation of platelet antiaggregating profile lead us to identify a new
      potent prototype of antiplatelet derivative, that is (6a) (IC(50)=2.3 microM),
      which acts in arachidonic acid pathway probably by inhibition of platelet COX-1
      enzyme. Additionally, the change of para-substituent group of acylhydrazone
      framework permitted us to identify hydrophilic carboxylate derivative (6g) and
      hydrophobic bromo derivative (6b) as two new leads of analgesics more active than
      dipyrone used as standard and with selective peripheral or central mechanism of
      action.

PMID- 15158784
TI  - A novel 3D-QSAR comparative molecular field analysis (CoMFA) model of imidazole
      and quinazolinone functionalized p38 MAP kinase inhibitors.
AB  - In this study we describe a new comparative molecular field analysis (CoMFA)
      model of dihydroquinazolinone and tetrasubstituted imidazole compounds with p38
      MAPK inhibitory activity. A series of 51 (a training set of 40 and a test set of
      11) dihydroquinazolinone [Bioorg. Med. Chem. Lett. 2003, 13, 277.] and
      tetrasubstituted imidazole [J. Med. Chem. 1999, 42, 2180.] derivatives known as
      p38 mitogen-activated protein kinase (p38 MAPK) selective inhibitors was studied
      by quantitative structure-activity relationship (3D-QSAR) analysis using
      comparative molecular field analysis. The 3D-QSAR models were generated and
      evaluated by a scheme that combines a genetic algorithm (GA) optimization with
      partial least squares (PLS) regression and by crossvalidation using the leave-one
      out technique. The model was able to efficiently predict the activities of the
      compounds of the test set, suggesting that it can be used for the planning of new
      p38 MAPK inhibitor candidates useful to treat chronic inflammatory states.

PMID- 15158785
TI  - Design, synthesis, and biological evaluation of novel 7-azaindolyl-heteroaryl
      maleimides as potent and selective glycogen synthase kinase-3beta (GSK-3beta)
      inhibitors.
AB  - Two approaches were developed to synthesize the novel 7-azaindolyl
      heteroarylmaleimides. The first approach was based upon the palladium-catalyzed
      Suzuki cross-coupling or Stille cross-coupling of 2-chloro-maleimide 5 with
      various arylboronic acids or arylstannanes. The second approach was based upon
      the condensation of ethyl 7-azaindolyl-3-glyoxylate 12 with various acetamides.
      The hydroxypropyl-substituted 7-azaindolylmaleimide template was first used to
      screen different heteroaryls attached to the maleimide. Replacement of
      hydroxypropyl with different chain lengths and different functional groups were
      studied next. Many compounds synthesized were demonstrated to have high potency
      at GSK-3beta, good GS activity in HEK293 cells and good to excellent metabolic
      stability in human liver microsomes. Three representative compounds (21, 33, and
      34) were demonstrated to have good selectivity against a panel of 80 kinase
      assays. Among them, compound 33 exhibited very weak inhibitions at the other 79
      kinase assays, and behaved as a highly selective GSK-3beta inhibitor.

PMID- 15158786
TI  - Synthesis and antiproliferative activity of 2,6-diamino-9-benzyl-9-deazapurine
      and related compounds.
AB  - Treatment of 6-bromomethyl- or 6-dibromomethyl-5-nitropyrimidine-2,4-diamine with
      KCN gave the same product--(2,6-diamino-5-nitropyrimidinyl)acetonitrile.
      Benzylation of the nitrile took place on the alpha-carbon to the cyano group
      preferentially affording the corresponding mono- and dibenzyl derivative, whose
      reductive cyclization resulted in 7-benzyl-5H-pyrrolo[3,2-d]pyrimidine-2,4
      diamine and 7,7-dibenzyl-7H-pyrrolo[3,2-d]pyrimidine-2,4,6-triamine,
      respectively. Suitability of the protection of N(2) and N(4) atoms with benzyl,
      acetyl, or benzoyl groups was also investigated. The in vitro evaluation of cell
      growth inhibition on CCRF-CEM, HL-60, HeLa S3, and L1210 cell lines showed
      significant activity in 8 new compounds. The most potent compounds were the above
      mentioned 6-dibromomethyl derivative (IC(50)=0.54, 1.7, 5.0, and 1.9 molL(-1))
      and 7,N(2),N(4)-tribenzyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine (IC(50)=1.9,
      2.7, 7.3, and 1.0 molL(-1)).

PMID- 15158787
TI  - Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2
      (phosphonomethoxy)ethoxy]pyrimidine and related compounds.
AB  - Synthesis of 2,4-diamino-5-cyano-6
      [[(diisopropoxyphosphoryl)methoxy]ethoxy]pyrimidine was based on the formation of
      the pyrimidine ring by cyclization followed by modification of the side chain by
      alkylation. The 5-cyano group was also transformed to a 5-formyl and 5
      hydroxymethyl group by reduction. As a side product an unexpected dimer was
      formed. Resulting compounds were converted to the free phosphonic acids by
      treatment with bromotrimethylsilane followed by hydrolysis. The 5-cyano and 5
      formyl derivatives showed pronounced antiretroviral activity, comparable to that
      of the reference drugs adefovir and tenofovir.

PMID- 15158788
TI  - Structural requirements of dictyopyrones isolated from Dictyostelium spp. in the
      regulation of Dictyostelium development and in anti-leukemic activity.
AB  - Cellular slime molds are fascinating to the field of developmental biology, and
      have long been used as excellent model organisms for the study of various aspects
      of multicellular development. We have recently isolated alpha-pyronoids, named
      dictyopyrones A-D (1-4), from various species of Dictyostelium cellular slime
      molds, and it was shown that compound 3 may regulate Dictyostelium development.
      In this study, we synthesized dictyopyrones A-D (1-4) and their analogues,
      investigated the physiological role of the molecules in cell growth and
      morphogenesis in D. discoideum, and further verified their effects on human
      leukemia K562 cells. Nitrogen-containing compounds 22 and 37 strongly inhibited
      cell growth in K562 leukemia cells, indicating that these compounds may be
      utilized as novel lead compounds for anti-leukemic agents.

PMID- 15158790
TI  - Reactions of some cyclopentenones with selected cysteine derivatives and
      biological activities of the product thioethers.
AB  - The conjugate addition reaction between glutathione, N-Boc-cysteine methyl ester,
      N-acetyl cysteine methyl ester and N-acetyl cysteine and several substituted
      cyclopentenones is described. The reversibility of this process was demonstrated
      by thio-adduct metathesis on treatment of the adduct with a different cysteinyl
      derivative. The levels at which these compounds inhibit the function of nuclear
      factor kappa B (NF-kappaB) and potentiate heat shock factor (HSF) are reported
      and the possible relevance of these studies concerning the antiviral and anti
      inflammatory activities of the cyclopentenone prostanoids is discussed.

PMID- 15158789
TI  - Design and synthesis of methyl 2-methyl-7,7-dihalo-5-phenyl-2
      azabicyclo[4.1.0]hept-3-ene-4-carboxylates with calcium channel antagonist
      activity.
AB  - A group of methyl 2-methyl-7,7-dihalo-5-(substituted-phenyl)-2
      azabicyclo[4.1.0]hept-3-ene-4-carboxylates were prepared by reaction of
      dihalocarbenes (:CX2, X = Br, Cl) with methyl 1-methyl-4-(substituted-phenyl)-1,4
      dihydropyridine-3-carboxylates. In vitro calcium channel antagonist activities
      were determined using a guinea pig ileum longitudinal smooth muscle assay. The
      title compounds exhibited weaker CC antagonist activity (10(-5)-10(-6)M range)
      than the reference drug nifedipine (1.4 x 10(-8)M). Structure-activity
      relationship studies showed that the position of a nitro substituent on the C-5
      phenyl ring where the relative potency order was ortho > meta > para, and the
      size and/or electronegativity of the C-7 geminal-dihalo substituents (Br > Cl),
      were determinants of calcium channel antagonist activity. This class of compounds
      did not exhibit any inotropic effect on guinea pig left atria. A
      dihalocyclopropyl moiety is a potential bioisostere for the 2-methyl-3
      methoxycarbonylvinyl moiety present in the calcium channel antagonist nifedipine.

PMID- 15158792
TI  - Induced circular dichroism spectra reveal binding of the antiinflammatory
      curcumin to human alpha1-acid glycoprotein.
AB  - This paper reports the first experimental evidence on binding of the plant
      derived curcumin molecule to human alpha1-acid glycoprotein (AGP), an acute phase
      protein in blood. Oppositely signed induced circular dichroism (CD) bands
      measured in the visible spectral region in pH7.4 phosphate buffer indicate that
      the protein binds this natural polyphenol molecule in a left-handed chiral
      conformation. Decreasing of the intrinsic fluorescence of AGP upon addition of
      curcumin confirmed the binding to take place. Fluorescence quenching titration
      curve of AGP allowed to calculate the association constant of the ligand (Ka = 4
      x 10(4) M(-1)). Modification of near UV CD spectrum of the protein suggests that
      curcumin induces changes in the tertiary structure of AGP, which leads to the
      decrease of binding affinity. By using rac-warfarin and amitriptyline, selective
      high affinity ligands of F1-S and A genetic variants of AGP, CD displacement
      experiments showed that curcumin is able to bind to both variants. Molecular
      docking calculations performed on curcumin-AGP and warfarin-AGP complexes suggest
      the existence of two alternative binding sites for curcumin; either at the open
      end of the central hydrophobic cavity or in a surface cleft of the protein.

PMID- 15158791
TI  - Radiosynthesis and pharmacological evaluation of [11C]EMD-95885: a high affinity
      ligand for NR2B-containing NMDA receptors.
AB  - EMD-95885, 6-[3-[4-(4-fluorobenzyl)piperidino]propionyl]-3H-benzoxazol-2-one (1)
      has been described as a selective antagonist for the NMDA receptors containing
      NR2B subunits, displaying an IC50 of 3.9 nM for this subtype. EMD-95885 (1) has
      been synthesized in good overall yield and labelled with carbon-11 ( T1/2 : 20.4
      min) at its benzoxazolinone moiety using [11C]phosgene. The pharmacological
      profile of [11C]EMD-95885 ([11C]-1) was evaluated in vivo in rats with
      biodistribution studies and brain radioactivity monitored with intracerebral
      radiosensitive beta-microprobes. The brain uptake of [11C]-1 was homogeneous (0.4
      0.6%ID/mL) across the different brain structures studied. This in vivo brain
      regional distribution of [11C]-1 was not consistent with the known distribution
      of NR2B subunits. Also as a measure of specificity the hippocampus/cerebellum
      ratio reached 0.8 throughout the time course of the experiment supporting the
      lack of specificity. Competition studies with the NR2B prototypic ligand
      ifenprodil and EMD-95885 (1), 30 min before the radioligand injection, displayed
      homogeneous reduction of [11C]-1 uptake of 40-60%. Pre-treatment of rats with DTG
      (sigma ligand), MDL105519 (glycine site antagonist) and MK801 (ion channel
      blocker) had no inhibitory effect on [11C]-1 uptake. Use of haloperidol as a
      blocking drug also resulted in a homogeneous inhibition of [11C]-1 uptake by 66
      60%, which does not reflect binding to dopamine or sigma receptors. Due to the
      homogeneous radioligand uptake and inhibition and no measure of cerebral blood
      flow effects during these blocking studies it is uncertain whether any specific
      binding is observed. In view of these results, [11C]EMD-95885 ([11C]-1) does not
      have the required properties for imaging NR2B containing NMDA receptors using
      positron emission tomography.

PMID- 15158793
TI  - Novel bicyclic sugar modified nucleosides: synthesis, conformational analysis and
      antiviral evaluation.
AB  - Methodology previously described by us was applied to the formation of novel
      conformationally restrained bicyclic sugar modified nucleosides, with
      introduction of an oxazole and a thiocarbamate ring at the 2('),3(')-positions of
      the ribonucleosides. Two novel alkyl derivatives of 2('),3(')-dideoxy-2('),3(')
      oxazole-beta-d-uridine and a novel uridine 2('),3(')-thiocarbamate were
      successfully synthesised. Conformational evaluation of all the synthesised
      compounds was conducted using the theoretical potential energy calculation via
      the macromodel v.6.0 molecular modelling programme. The conformationally
      restrained nucleosides described were evaluated against a wide range of DNA and
      RNA viruses. None of the compounds showed specific antiviral effects at subtoxic
      concentrations.

PMID- 15158794
TI  - Versatile approach for the synthesis of novel seven-membered iminocyclitols via
      ring-closing metathesis dihydroxylation reaction.
AB  - Seven-membered iminocyclitols with diverse diastereomers were prepared starting
      with d- and l-serines and employing ring-closing olefin metathesis and
      dihydroxylation reaction sequence. The iminocyclitols were assayed for
      glycosidase inhibition and compound 20 was found to be a competitive inhibitor
      for beta-glucosidase with Ki 26.3 microM.

PMID- 15158795
TI  - Paclitaxel-HSA interaction. Binding sites on HSA molecule.
AB  - Paclitaxel (trade name Taxol) is one of the world's most effective anticancer
      drugs. It is used to treat several cancers including tumours of the breast, ovary
      and lung. In the present work the interaction of paclitaxel with human serum
      albumin (HSA) in aqueous solution at physiological pH has been investigated
      through CD, fluorescence spectroscopy and by the antibody precipitate test.
      Binding of paclitaxel to albumin impact on protein structure and it influences
      considerably albumin binding of other molecules like warfarin, heme or bilirubin.
      The paclitaxel-HSA interaction causes the conformational changes with the loss of
      helical stability of protein and local perturbation in the domain IIA binding
      pocket. The relative fluorescence intensity of the paclitaxel-bound HSA
      decreased, suggesting that perturbation around the Trp 214 residue took place.
      This was confirmed by the destabilization of the warfarin binding site, which
      includes Trp 214, and high affinity bilirubin binding site located in subdomain
      IIA.

PMID- 15158796
TI  - Polymeric and dendrimeric pyridoxal enzyme mimics.
AB  - Pyridoxal was covalently attached to polyethylenimine polymers, but the resulting
      materials were found to degrade rapidly. In comparison, the dendrimeric
      pyridoxals, which possess only one pyridoxal unit at the core of every dendrimer
      molecule were found to be relatively stable compounds. A total of 12
      poly(amidoamine) type dendrimers were synthesized. They range from G1 to G6 with
      either NMe(2) or NHAc termini. The NMe(2)-terminated pyridoxal dendrimers
      racemize alpha-amino acids 50-100 times faster than does simple pyridoxal, while
      the NHAc-terminated pyridoxal dendrimers racemize alpha-amino acids only 3-5
      times faster than does simple pyridoxal. Both the NMe(2)- and NHAc-terminated
      pyridoxal dendrimers decarboxylate 2-amino-2-phenyl-propionic acid 1-3 times
      faster than simple pyridoxal. The interior polarity in the pyridoxal dendrimers
      is similar to that of 85:15 water-DMF solution. Furthermore, we successfully
      incorporated eight lauryl groups to the G5 pyridoxal dendrimer at known
      positions. The laurylated dendrimer exhibits lower racemization and
      decarboxylation rates than do the unlaurylated ones, in contrast to the positive
      rate effects of laurylation in polyethylenimine-pyridoxamines in our previous
      transamination studies.

PMID- 15158798
TI  - Chiral, nonracemic (piperazin-2-yl)methanol derivatives with sigma-receptor
      affinity.
AB  - Starting with the proteinogenic amino acid (S)-serine a series of chiral
      nonracemic (piperazin-2-yl)methanols 3 with various N-4 substituents is
      described. The key step in the synthesis of 3 is the reaction of the
      chloroacetamide 5 with various primary amines to yield the diastereomeric
      bicyclic piperazinediones cis-6 and trans-6. The scope and limitation of this
      transformation is thoroughly investigated. The alpha1- and sigma2-receptor
      affinities of the piperazines 3 are determined in receptor binding studies with
      guinea pig brain and rat liver membrane preparations using [3H]-labeled (+)
      pentazocine and ditolylguanidine, respectively. It was found, that an additional
      phenyl residue in the N-4 substituent is favorable to high sigma1-receptor
      affinity. In this series the p-methoxybenzyl substituted piperazine 3d reveals
      the highest sigma1-receptor affinity (Ki=12.4 nM) with selectivity toward sigma2
      , NMDA-, kappa-opioid, and mu-opioid receptors.

PMID- 15158797
TI  - Parallel synthesis of a library of bidentate protein tyrosine phosphatase
      inhibitors based on the alpha-ketoacid motif.
AB  - Protein tyrosine phosphatases (PTPases) regulate intracellular signal
      transduction pathways by controlling the level of tyrosine phosphorylation in
      cells. These enzymes play an important role in a variety of diseases including
      type II diabetes and infection by the bacterium Yersinia pestis, which is the
      causative agent of bubonic plague. This report describes the synthesis, using
      parallel solution-phase methods, of a library of 104 potential inhibitors of
      PTPases. The library members are based on the bis(aryl alpha-ketocarboxylic acid)
      motif that incorporates a carboxylic acid on the central benzene linker. This
      carboxylic acid was coupled with a variety of different aromatic amines through
      an amide linkage. The aromatic component of the resulting amides is designed to
      make contacts with residues that surround the active site of the PTPase. The
      library was screened against the Yersinia PTPase and PTP1B. Based upon the
      screening results, four members of the library were selected for further study.
      These four compounds were evaluated against the Yersinia PTPase, PTP1B, TCPTP,
      CD45, and LAR. Compound 14 has an IC(50) value of 590nM against PTP1B and is a
      reversible competitive inhibitor. This affinity represents a greater than 120
      fold increase in potency over compound 2, the parent structure upon which the
      library was based. A second inhibitor, compound 12, has an IC(50) value of 240nM
      against the Yersinia PTPase. In general, the selectivity of the inhibitors for
      PTP1B was good compared to LAR, but modest when compared to TCPTP and CD45.

PMID- 15158799
TI  - Definition of an electronic profile of compounds with inhibitory activity against
      hematin aggregation in malaria parasite.
AB  - Malaria is one of the most important parasitic diseases, affecting almost half of
      the world and posing a threat to the other half. Xanthone derivatives can behave
      as antimalarial drugs in the same mechanistic way as chloroquine and other
      related quinolines. This action is due to the inhibition of the detoxification
      pathway of the parasite, responsible for the production of hemozoin. We report a
      study of the electronic properties of the xanthonic and quinolinic compounds
      based on DFT calculations, in order to determine a pattern that could be applied
      to the development of new potentially active antimalarial molecules. As a result,
      a new interpretation of structure-activity relationship of the quinoline
      antimalarial drugs, and of the active hydroxylated xanthones is proposed here. We
      conclude that electronic features rather than steric factors control primarily
      the inhibitory activity of the studied compounds against hematin aggregation,
      concurring to a potential antimalarial activity.

PMID- 15158800
TI  - QSAR modeling of globulin binding affinity of corticosteroids using AM1
      calculations.
AB  - A quantitative structure-activity analysis of binding affinity of a series of 30
      steroids for corticosteroid-binding globulin was performed using Wang-Ford
      charges of the non-hydrogen common atoms obtained from molecular electrostatic
      potential surface of AM1 optimized energy-minimized geometries of the compounds.
      Attempts were made to include lipophilicity (logP) and molar refractivity (MR)
      values of the whole molecules in the multivariate relations. The final relations
      were subjected to 'leave-one-out' cross-validation to check their predictive
      potential. It was found from the study that the charges of different atoms of the
      steroid nucleus [atoms 3, 4, 5 (ring A), 8, 9 (fusion points of rings B and C)
      and 16 (ring D)] contribute significantly to the binding affinity. This suggests
      the importance of these atoms/sites for the globulin binding affinity, which is
      also supported by previous reports on structure-activity relations of
      corticosteroids. Further, molar refractivity shows parabolic relation with the
      binding affinity, which indicates the possibility of dispersion interactions. The
      statistical qualities of the final equations generated in the present study
      (predicted variance 77-82%; explained variance 83-87%) are better than those of
      some of the previously reported models.

PMID- 15158801
TI  - Two novel antibiotics, Sch 419558 and Sch 419559, produced by Pseudomonas
      fluorescens: effect on activity by overexpression of RpoE.
AB  - Two new secondary metabolites designated as Sch 419558 (1) and Sch 419559 (2),
      were isolated from the fermentation broth of Pseudomonas fluorescens. Structure
      elucidation of 1 and 2 was accomplished by spectroscopic data analyses including
      MS and NMR experiments. Both compounds were identified as lipopeptides containing
      valine and threonine linked with 1-amino-1-hydroxy-heptadec-9-en-2-one or 1-amino
      1-hydroxy-pentadecan-2-one carbon chains, respectively. Characterization of the
      amino acids was further confirmed by amino acid analysis. Compounds 1 and 2
      exhibited antibacterial activity against a sensitized E. coli strain with minimum
      inhibitory concentration of 0.3 and 0.6 microg/mL, respectively. Overexpression
      of RpoE in the E. coli strain increased the MIC over 60-fold for compounds 1 and
      2.

PMID- 15158802
TI  - Antitumor agents. Part 227: Studies on novel 4'-O-demethyl-epipodophyllotoxins as
      antitumor agents targeting topoisomerase II.
AB  - Eight novel epipodophyllotoxin derivatives (6-13), which were designed to
      overcome drug resistance and enhance topoisomerase II inhibition, were
      synthesized and evaluated. Two of these compounds (7 and 8) showed better
      preclinical activity profiles, including cell growth inhibition, cell killing,
      and in vitro topoisomerase II inhibition, as compared to the prototype molecule
      etoposide (1). They also retained the superior drug-resistance profile of GL-331
      (4), an epipodophyllotoxin derivative currently in clinical evaluation.

PMID- 15158803
TI  - GABA receptor antagonists and insecticides: common structural features of 4-alkyl
      1-phenylpyrazoles and 4-alkyl-1-phenyltrioxabicyclooctanes.
AB  - Fipronil [5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4
      trifluoromethylsulfinylpyrazole] is one of the most important insecticides.
      Structure-activity studies described here reveal that fipronil retains its very
      high binding potency at the human beta3 and house fly gamma-aminobutyric acid
      (GABA) receptors and toxicity to house flies on replacing the pyrazole
      trifluoromethylsulfinyl moiety with tert-butyl or isopropyl and the phenyl
      trifluoromethyl substituent with ethynyl, trifluoromethoxy, bromo or chloro.
      Among the compounds studied, those with other alkyl groups at the 4-position of
      the pyrazole, as well as phenyl substitution without one or both of the 2,6
      dichloro groups, are less effective. 5-Amino-4-tert-butyl-3-cyano-1-(2,6-dichloro
      4-ethynylphenyl)pyrazole is highly effective and almost isosteric with 4-tert
      butyl-3-cyano-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane (the most
      potent 4-alkyl-1-phenyltrioxabicyclooctane) as a noncompetitive GABA antagonist
      and insecticide. These findings are interpreted as three binding subsites in the
      GABA receptor: a hydrophobic site undergoing steric interaction with the tert
      butyl or equivalent group; a hydrogen bonding site to pyrazole N-2; a pi bonding
      site to the face of the phenyl moiety; with supplemental enhancement by the 3
      cyano and 4-ethynyl substituents.

PMID- 15158804
TI  - Omega-pyridiniumalkylethers of steroidal phenols: new compounds with potent
      antibacterial and antiproliferative activities.
AB  - Novel omega-pyridiniumalkylethers of two steroidal phenols were synthesized as
      compounds with potential antimicrobial activity. 3-Hydroxy-estra-1,3,5(10)-triene
      17-one and 1-hydroxy-4-methyl-estra-1,3,5(10)-triene-17-one were reacted with
      omega,omega'-dibromoalkanes to omega-bromoalkoxy-estra-1,3,5(10)-trienes followed
      by reaction with pyridine to obtain the desired steroidal omega-pyridiniumalkoxy
      compounds as bromides. Their antimicrobial activity against strains of
      multiresistant Staphylococcus aureus (MRSA), a vancomycin resistant Enterococcus
      faecalis and fast growing mycobacteria depends clearly on the length of the alkyl
      chain. A strong broadband activity has been found for the compounds with eight or
      10 C-atoms; in some cases better than ciprofloxacin or cetylpyridinium salts. In
      addition, the antiproliferative and cytotoxic activity depends on the chain
      length, too. The differentiation between antibacterial and cytotoxic activity is
      better for the steroid hybrid molecules than the cetylpyridinium salts. These new
      compounds can serve as lead compounds for further optimization.

PMID- 15158805
TI  - Antitumor agents. Part 235: Novel 4'-ester etoposide analogues as potent DNA
      topoisomerase II inhibitors with improved therapeutic potential.
AB  - Eight 4'-ester epipodophyllotoxin derivatives (9-16) were designed and
      synthesized with the aim to overcome drug-resistance and improve water-solubility
      simultaneously. These compounds were superior to etoposide (1) in causing
      cellular protein-linked DNA breaks and inhibiting KB and 1-resistant KB-7d cell
      replication. Compounds 9 and 10 showed significant inhibitory activity against
      DNA topoisomerase II in vitro. Compound 10 also exhibited an in vitro DNA
      cleavage pattern similar to that of GL-331 (5). A hypothetical model on the
      action mode of 1-analogues is proposed based on the results.

PMID- 15158806
TI  - Lipase-mediated stereoselective hydrolysis of stampidine and other
      phosphoramidate derivatives of stavudine.
AB  - Enzymatic hydrolysis of stampidine and other aryl phosphate derivatives of
      stavudine were investigated using the Candida Antarctica Type B lipase. Modeling
      studies and comparison of the hydrolysis rate constants revealed a chiral
      preference of the lipase active site for the putative S-stereoisomer. The in
      vitro anti-HIV activity of these compounds correlated with their susceptibility
      to lipase- (but not esterase-) mediated hydrolysis. We propose that stampidine
      undergoes rapid enzymatic hydrolysis in the presence of lipase according to the
      following biochemical pathway: During the first step, hydrolysis of the ester
      group results in the formation of carboxylic acid. Subsequent step involves an
      intramolecular cyclization at the phosphorous center with simultaneous
      elimination of the phenoxy group to form a cyclic intermediate. In the presence
      of water, this intermediate is converted into the active metabolite Ala-d4T-MP.
      We postulate that the lipase hydrolyzes the methyl ester group of the l-alanine
      side chain to form the cyclic intermediate in a stereoselective fashion. This
      hypothesis was supported by experimental data showing that chloroethyl
      substituted derivatives of stampidine, which possess a chloroethyl linker unit
      instead of a methyl ester side chain, were resistant to lipase-mediated
      hydrolysis, which excludes the possibility of a direct hydrolysis of stampidine
      at the phosphorous center. Thus, our model implies that the lipase-mediated
      formation of the cyclic intermediate is a key step in metabolism of stampidine
      and relies on the initial configuration of the stereoisomers.

PMID- 15158807
TI  - Bisubstrate analogue structure-activity relationships for p300 histone
      acetyltransferase inhibitors.
AB  - p300 and CBP are important histone acetyltransferases (HATs) that regulate gene
      expression and may be anti-cancer drug targets. Based on a previous lead
      compound, Lys-CoA, we have used solid phase synthesis to generate a series of 11
      new analogues and evaluated these compounds as HAT inhibitors. Increased spacing
      between the CoA moiety and the lysyl moiety generally decreases inhibitory
      potency. We have found two substituted derivatives that show about 4-fold
      increased potency compared to the parent compound Lys-CoA. These structure
      activity studies allow for a greater understanding of the optimal requirements
      for potent inhibition of HAT enzymes and pave the way for a novel class of anti
      cancer therapeutics.

PMID- 15158810
TI  - [An example of hospital-based pharmacoepidemiology in paediatrics: tolerance to
      fluoroquinolones].

PMID- 15158808
TI  - QSAR and ADME.
AB  - The prediction from structure of ADME (absorption, distribution, metabolism,
      elimination) of drug candidates is an important goal to achieve since it can
      considerably reduce the cost of drug development. Using our database of 10,700
      QSAR, we are now reaching the point where we can make many useful comparisons
      that illustrate how ADME is a practical way to describe the way organic compounds
      react with living systems. We also show that Caco-2 cells are useful to model
      absorption, but the most generally useful parameter is the octanol/water
      partition coefficient. It should be noted, however, that in our opinion, an in
      silico prediction of ADME is still a long way in the future.

PMID- 15158811
TI  - [Systemic lupus erythematosus of paediatric onset: long-term follow-up of a
      cohort including 104 patients (1975-1985)].

PMID- 15158812
TI  - [Renal involvement in systemic lupus in children: when and how to screen?].

PMID- 15158813
TI  - [Cutaneous manifestations of lupus in children].

PMID- 15158814
TI  - [Disseminated lupus erythematosus: new pathophysiological and therapeutic
      approaches].

PMID- 15158815
TI  - [Lung development and malformations].

PMID- 15158816
TI  - [Lung abnormalities: from fetus to adult, which management: prenatal diagnosis
      and prognosis].

PMID- 15158817
TI  - [Long-term outcome of lung malformation in children].

PMID- 15158818
TI  - [Mechanisms of action of psychoactive substances during brain ontogenesis].

PMID- 15158819
TI  - [Children born to drug addicted mothers].

PMID- 15158820
TI  - [Neurodevelopment of children exposed to antiepileptic drugs and psychoactive
      medication during pregnancy].

PMID- 15158821
TI  - [Organ transplantation in children].

PMID- 15158822
TI  - [Trends for immunosuppression concepts in organ transplantation].

PMID- 15158823
TI  - [Transplantation using reduced organs].

PMID- 15158824
TI  - [Request for organ donation in intensive care medicine].

PMID- 15158825
TI  - [Digestive tract immunology and Crohn disease].

PMID- 15158826
TI  - [Bacterial colonization of the intestine in young children and immune system
      modulation].

PMID- 15158827
TI  - [Diagnosis and global management of children with neurofibromatosis 1].

PMID- 15158828
TI  - [Contributions of research to the understanding learning disorders in
      neurofibromatosis type 1].

PMID- 15158829
TI  - [Specificity of benign and malignant tumoral complications of type 1
      neurofibromatosis].

PMID- 15158830
TI  - [Orthopaedic complications of neurofibromatosis].

PMID- 15158831
TI  - [Genetics and the SHOX gene].

PMID- 15158832
TI  - [Puberty in girls with Turner syndrome].

PMID- 15158833
TI  - [Health in young adult women with Turner syndrome in France].

PMID- 15158834
TI  - [From morphological features to diagnostics of unexplained mental retardation: a
      new clinical classification?].

PMID- 15158835
TI  - [Usefulness of neurological examination].

PMID- 15158836
TI  - [Diagnostic approach in patients with severe and syndromic mental retardation].

PMID- 15158837
TI  - [X-linked mental retardation: a continuous spectrum from syndromic forms towards
      non-specific forms].

PMID- 15158838
TI  - [Intestinal flora: development, characteristics and influence of the type of
      feeding].

PMID- 15158839
TI  - [Biological effects of intestinal flora modifiers].

PMID- 15158840
TI  - [Low-grade glial tumours].

PMID- 15158841
TI  - [Radiation therapy for brain tumours in children].

PMID- 15158842
TI  - [Use of procalcitonin at the pediatric emergency room].

PMID- 15158843
TI  - [Procalcitonin and neonatal infection].

PMID- 15158844
TI  - [Procalcitonin in pediatric resuscitation].

PMID- 15158845
TI  - [Status of tobacco prevention practices in ambulatory and hospital care].

PMID- 15158846
TI  - [Balance between precautionary principle and adolescence process: thoughts of
      pediatric psychiatry].

PMID- 15158847
TI  - [Which role for education in tobacco smoking prevention among adolescents?].

PMID- 15158848
TI  - [Education aspects of smoking prevention: how to communicate with adolescents?].

PMID- 15158849
TI  - [Preclinical models for hepatocyte transplantation].

PMID- 15158850
TI  - [Diagnostic approach in oral disorder in young children].

PMID- 15158852
TI  - [Post-traumatic anorexia: challenging multidisciplinary management].

PMID- 15158854
TI  - [Indications for early intervention in the prevention and management of
      neurodevelopmental disorders].

PMID- 15158855
TI  - [Which kind of early intervention for neurodevelopmental disorders?].

PMID- 15158856
TI  - [Can the impact of early intervention be demonstrated and how should it be
      done?].

PMID- 15158857
TI  - [Does early intervention improve the prognosis of disabled children? Report of
      1700 families].

PMID- 15158858
TI  - [Obesity in adolescents: activism, pessimism, realism?].

PMID- 15158859
TI  - [Obesity in adolescence. A childhood story...].

PMID- 15158860
TI  - [Management of obesity in adulthood: point of view of the adult's physician].

PMID- 15158862
TI  - [Obesity in adolescents: which are the treatment objectives? Point of view of the
      adolescents' physician].

PMID- 15158861
TI  - [Management of common obesity in adolescents: point of view of the pediatric
      nutritionist].

PMID- 15158864
TI  - [Fetal cardiology].

PMID- 15158863
TI  - [Prevention Obesity 94: an example of realistic procedure].

PMID- 15158865
TI  - [Management of congenital heart diseases using interventional catheterism].

PMID- 15158866
TI  - [Surgery for congenital heart diseases].

PMID- 15158867
TI  - [Which kind of congenital heart disease may allow a normal life in children?].

PMID- 15158868
TI  - [Problems associated with congenital heart disease during adolescence and
      adulthood].

PMID- 15158869
TI  - [Professional rehabilitation of adults with congenital heart disease].

PMID- 15158870
TI  - [Increasing number of twins and its consequences on health at birth].

PMID- 15158871
TI  - [Polymorphism of twin pregnancy: anatomic-clinical forms].

PMID- 15158872
TI  - [Mortality and morbidity among twins].

PMID- 15158873
TI  - [Perinatal death in a twin: living between loss and attachment].

PMID- 15158874
TI  - [Psychological impact of the birth of twins on children and their parents].

PMID- 15158875
TI  - [Indication for digestive endoscopy in gastro-oesophageal reflux in children].

PMID- 15158876
TI  - [Gastroesophageal reflux in children: indications of non-endoscopic
      investigations].

PMID- 15158877
TI  - [Are prokinetic drugs still indicated for gastro-oesophageal reflux in
      children?].

PMID- 15158878
TI  - [Should proton pump inhibitors be prescribed in cases other than peptic
      esophagitis?].

PMID- 15158879
TI  - [Epidemiology of poisoning in children].

PMID- 15158880
TI  - [Severe poisoning: management in pediatric resuscitation].

PMID- 15158881
TI  - [Management of acute accidental poisoning in children].

PMID- 15158882
TI  - [New forms of poisoning in children].

PMID- 15158883
TI  - [Apparent life threatening event in infants].

PMID- 15158884
TI  - [Apparent life threatening event in infants: clinical rationale for
      gastrointestinal tract investigations].

PMID- 15158885
TI  - [Apparent life threatening events in infants: rationale for cardiac
      investigations].

PMID- 15158886
TI  - [Causes of apparent life threatening events in infants: questions, exams,
      investigations for clinical use].

PMID- 15158887
TI  - [Guidelines, consensus and quality of care: what are we talking about?].

PMID- 15158888
TI  - [Field application of consensus statements: the example of rhinopharyngitis].

PMID- 15158889
TI  - [Management of acute bronchiolitis in infants].

PMID- 15158890
TI  - [Limitation for the use of guidelines: an example of oral rehydratation
      solutions].

PMID- 15158891
TI  - [Volume expansion in children].

PMID- 15158892
TI  - [Fluids and vascular access for emergency plasma volume expansion].

PMID- 15158893
TI  - [Emergency fluid resuscitation: errors and traps].

PMID- 15158894
TI  - [Fluid resuscitation in pediatric emergencies. Traps and errors].

PMID- 15158895
TI  - The use of dynamic vapour sorption and near infra-red spectroscopy (DVS-NIR) to
      study the crystal transitions of theophylline and the report of a new solid-state
      transition.
AB  - This study was undertaken to see if the combined technique of DVS-NIR could add
      to the understanding of transitions between physical forms of theophylline. There
      was excellent correlation between the mass changes and the intensity of the NIR
      peaks, showing that the hydrate was being formed and lost. This was characterised
      by the peaks at 1478 and 1972 nm representing an -OH deformation. NIR spectra for
      desorption shows that the dehydrate retains partial structure of both the
      anhydrate and hydrate crystal lattices. During rehydration of the dehydrate a new
      transition was discovered. An unexpected mass loss occurred between 40 and 50%
      RH. Usually, a mass loss during water sorption is characteristic of
      crystallisation of an amorphous material, although in this case it could be that
      the sample is crystalline. NIR data showed that during this transition the
      dehydrate peaks reverted back to the peak positions seen for anhydrous
      theophylline. The absorption of water into the dehydrate allowed the freedom of
      movement for the stable anhydrous lattice to form. It was concluded that DVS-NIR
      is a useful tool to study solid-state transitions and that the transition exists
      for conversion of theophylline dehydrate to anhydrate which is facilitated
      through water sorption.

PMID- 15158896
TI  - Insulin microcrystal suspension as a long-acting formulation for pulmonary
      delivery.
AB  - Pulmonary delivery provides the most promising non-parenteral route of insulin
      administration. Insulin was used as a model protein to demonstrate the
      feasibility of using protein crystals for the pulmonary delivery of a sustained
      release protein drug formulation. Insulin microcrystals with a mean diameter of 3
      microm were prepared using a seed zone method. The yield of crystallization was
      very high (95.8 +/- 0.97%), and the microcrystals were recovered with high
      efficiency (>98%) by centrifugation. Morphological examination using scanning
      electron microphotography showed the microcrystals to be of a homogeneous
      rhombohedral shape, with some rhombus forms, without aggregates. After the
      administration of 32 U/kg of the microcrystal suspension to STZ-induced diabetic
      SD rats by intratracheal instillation, the blood glucose levels were reduced and
      hypoglycemia was prolonged over 13 h, as compared to the insulin solution. The
      percent minimum reductions of the blood glucose concentration (% MRBG) produced
      by the microcrystal suspension and insulin solution reached 36.5 and 37.2%,
      respectively, of the initial level, and the percent total reductions in blood
      glucose (% TRBG(13 h)) were 34.4 and 25.0%, respectively. In the case of
      inhalation using a sieve-type ultrasonic nebulizer, the % MRBG produced by the
      microcrystal suspension and insulin solution were 21.7 and 26.3%, respectively,
      of the initial level, and the % TRBG(13 h) were 66.7 and 58.4%, respectively.
      However, the hypoglycemic effects of the microcrystal suspension were prolonged
      over 7 h, which compares favorably with the insulin solution (P<0.5 by unpaired t
      test). These results could be attributed to the sustained-release of insulin from
      the microcrystals, which were deposited widely throughout the entire lung.

PMID- 15158897
TI  - Influence of the punch diameter and curvature on the yield pressure of MCC
      compacts during Heckel analysis.
AB  - The volume reduction behaviour of powders has been quantified by means of the 'in
      die' yield pressure (YP) using Heckel analysis. However, because different YPs
      are reported for the same material, the experimental conditions influencing this
      material-constant were investigated. Silicified microcrystalline cellulose was
      compressed into flat-faced and convex tablets using a compaction simulator
      instrumented with load and displacement transducers. During compression, upper
      and lower punch force and displacement data were recorded and corrected for punch
      deformation. A symmetrical triangle wave compression profile was used and the
      instantaneous punch velocity was kept constant (5mm/s). Individual tablet height
      and weight were used for Heckel analysis. The influence of the 'effective
      compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD)
      (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was
      statistically evaluated using Response Surface Modelling software. A quadratic
      surface response equation, describing the relationship between P(EFF), PD, FD and
      YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced
      (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly
      determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor
      influence on the YP, although more pronounced for the concave punches. The method
      used resulted in reproducible P(EFF) and tensile strength values and the flat
      faced tablets showed less weight variation. Flat-faced punches are preferred over
      punches with a concave surface when investigating the volume reduction behaviour
      of a powder by means of Heckel analysis and the experimental parameters should be
      reported.

PMID- 15158898
TI  - Solid-state characterization of rifampicin samples and its biopharmaceutic
      relevance.
AB  - Polymorphism of rifampicin has been postulated to be responsible for its variable
      bioavailability from solid oral dosage forms. In this regard, it was believed
      that form II is the preferred form and the content of amorphous needs to be
      critically monitored. However, there was no study in literature that determines
      solubility advantage associated with rifampicin polymorphs and further the
      desired raw material characteristics for the consistent bioavailability. Hence,
      this investigation was undertaken with an objective to determine biopharmaceutic
      relevance of rifampicin physical forms and to propose critical raw material
      specifications for rifampicin bulk material. For this purpose, solid-state
      properties of standard form I, form II, amorphous and commercial samples acquired
      from rifampicin manufacturers were characterized by differential scanning
      calorimetry (DSC), Fourier transformed infrared spectroscopy (FTIR), hot stage
      microscopy (HSM), thermogravimetric analysis (TGA), powder X-ray diffraction (p
      XRD), solid-state nuclear magnetic resonance (NMR) and molecular modelling. In
      addition, intrinsic dissolution of standard samples, powder dissolution as well
      as particle size distribution of all the samples and powder dissolution of
      various sieve fraction of commercial samples were done in order to study the
      influence of polymorphism and other factors on rate and extent of dissolution. It
      was found that rifampicin in commercial bulk samples exist as various
      combinations of form I, form II and amorphous. As physical forms show comparable
      intrinsic dissolution rate (IDR) at all the pH values, solubility advantage
      associated with rifampicin polymorphs is negligible. Nevertheless, powder
      dissolution of commercial samples was influenced by particle size. In powder
      dissolution of different sieve fractions of commercial samples, fine particles
      below 100 microm have shown high rate and extent of dissolution irrespective of
      polymorphic content, whereas particles above 100 microm exhibited reduced
      dissolution. In intrinsic dissolution, thermodynamically unstable form II
      exhibited lower IDR than stable form I. Further, this difference is evident only
      at pH 2.0 and at all other pH values there was no difference in IDR of these two
      forms. For this unexpected finding, two hypotheses based on differences in H
      bonding of the polymorph have been proposed.

PMID- 15158899
TI  - Modified particle swarm optimization algorithm for variable selection in MLR and
      PLS modeling: QSAR studies of antagonism of angiotensin II antagonists.
AB  - A version of modified particle swarm optimization (PSO) algorithm has been
      proposed. The PSO algorithm has been modified to adopt to the discrete
      combinatorial optimization problem and reduce the probability of sinking into
      local optima. In the modified PSO algorithm, the velocity represents the
      probability of element in each particle taking value 1 or 0. The modified
      discrete PSO algorithm is proposed to select variables in MLR and PLS modeling
      and to predict antagonism of angiotensin II antagonists. The modified C(p) is
      employed as fitness function. The results were compared to those obtained by GAs.
      Experimental results have demonstrated that the modified PSO is a useful tool for
      variable selection which converges quickly towards the optimal position.

PMID- 15158901
TI  - Food effects on tablet disintegration.
AB  - The aims of the present study was to investigate if food components, as
      represented by a multi-component nutritional drink for tube feeding, could affect
      tablet disintegration of standard tablets in vitro as well as in vivo and propose
      a mechanism for potential food effects on tablet disintegration. The tablet
      disintegration was delayed between 5 min and more than 1h in the simulated
      gastric fed medium compared to a simple buffer. This effect was dependent on the
      tablet composition. A similar delay in tablet disintegration was also found in
      vivo after administration of the nutritional drink to three Labradors as observed
      by removing the tablet from the stomach at different times through a gastric
      fistula. The delay in tablet disintegration appeared to be caused by
      precipitation of a film, mainly consisting of protein, on the tablet surface as
      indicated by disintegration studies with pure nutrients, identification by IR
      spectroscopy of contents of precipitates obtained in a model study were the
      nutrients were incubated with different tablet excipients and visual observations
      of tablets exposed to the simulated fed medium. The drug dissolution of a soluble
      compound, metoprolol tartrate, from a standard tablet was also strongly delayed
      in the simulated fed medium. In conclusion, food, could significantly delay
      tablet disintegration and drug dissolution in the stomach by formation of a film
      around the tablets. This effect could be monitored by a simple in vitro
      disintegration test using a test medium based on a nutritional drink. More
      studies are needed to investigate the significance of the slow tablet
      disintegrations on bioavailability and for which types of food the present effect
      occurs.

PMID- 15158900
TI  - Lipophilicity-related inhibition of blood platelet aggregation by nipecotic acid
      anilides.
AB  - Using N-[4-(hexyloxy)phenyl]piperidine-3-carboxamide (17c) as a structural lead,
      a number of isomers, derivatives, and ring-opened analogs were synthesized and
      tested for their ability to block the in vitro aggregation of human platelets
      induced by adenosine 5'-diphosphate (ADP). For the most active compounds,
      inhibition of the platelet aggregation triggered by arachidonic acid (AA) and ADP
      induced intraplatelet calcium mobilization was also demonstrated. Based on
      quantitative structure-activity relationships (QSARs), we proved the impact of
      hydrophobicity on antiplatelet activity by a nonlinear (parabolic or bilinear)
      relationship between pIC(50) and lipophilicity, as assessed by RP-HPLC capacity
      factors and ClogP (i.e. calculated 1-octanol-water partition coefficients). This
      study highlighted the following additional SARs: quasi-isolipophilic isomers of
      17c (isonipecotanilides and pipecolinanilides) and ring-opened analogs (e.g.
      anilide of beta-alanine) exhibited lower antiplatelet activity; methylation of
      the piperidine nitrogen of 17c has no effect, whereas alkylation with an n-propyl
      group decreases the activity by a factor of approximately 2, most likely due to a
      conformation-dependent decrease in lipophilicity.

PMID- 15158902
TI  - Influence of particle size and shape on flowability and compactibility of binary
      mixtures of paracetamol and microcrystalline cellulose.
AB  - The influence of the size and shape of paracetamol particles on the flow and
      compression behavior of blends (1:1) of microcrystalline cellulose (MCC) was
      investigated. The effect of paracetamol particle shape was investigated by using
      two differently prepared samples, micronized and novel engineered Solution
      Atomization and Xstallization by Sonication (SAXS) particles, which exhibited
      similar particle size ranges (2-6 microm). The results were compared to data
      obtained for an untreated paracetamol sample. The blends containing SAXS
      particles exhibited increased bulk and tapped density and improved flow, compared
      to the blend containing micronized particles. This may reflect differences in
      shape since the SAXS particles exhibited spherical morphology. The
      compressibility of the blend containing untreated paracetamol was greater than
      blends containing the SAXS and micronized materials, which may reflect the
      different drug particle sizes and shapes. However, blends containing the needle
      shaped particles of pure untreated sample, exhibited poor compactibility after
      storage at 10% RH. It was found that increasing the moisture content in the
      blends by storage at 44% RH resulted in an increase in the compactibility of the
      samples containing untreated and SAXS paracetamol with the blends containing
      micronized paracetamol being relatively unaffected. In general, tablets prepared
      from blends containing smaller particles of paracetamol exhibited significantly
      greater compactibility compared to tablets prepared containing the larger
      particle sized untreated paracetamol. The use of small, spherical drug particles
      may result in improvements in the bulk density, densification and compactibility
      of blends of paracetamol and microcrystalline cellulose.

PMID- 15158903
TI  - Reversible, temperature-dependent, and AM404-inhibitable adsorption of anandamide
      to cell culture wells as a confounding factor in release experiments.
AB  - Relatively little is known about the process whereby the endocannabinoid
      anandamide (AEA) is released from cells. A simple way of studying this process is
      to sample the appearance in the medium of tritium following preloading of cells
      with [(3)H]AEA under conditions where its metabolism is prevented. However, this
      approach may be complicated by the ability of AEA to be adsorbed reversibly to
      the cell culture wells. In the present study, it is found that cell culture wells
      adsorb almost half of the added AEA in a manner prevented by fatty acid-free
      bovine serum albumin, and by the prototypical uptake inhibitors AM404 and VDM11
      with IC(50) values of 3 and 1 microM, respectively. After incubation followed by
      washing of the plates, AEA is released into the medium from the wells by a first
      order process (K approximately 0.1 min(-1)) that is temperature-dependent and
      increased by AM404 and fatty acid-free bovine serum albumin. When assays were run
      with 0.15% fatty acid-free bovine serum albumin during the loading, washing and
      release phases of the assay, the release from the well was greatly reduced and a
      first order, temperature-sensitive release from C6 glioma cells could be
      unmasked. It is concluded that the reversible adsorption of AEA by cell culture
      wells can be a confounding factor in release experiments.

PMID- 15158904
TI  - Compression behaviour and tablet-forming ability of spray-dried amorphous
      composite particles.
AB  - The aim of this study was to investigate the compression behaviour and tablet
      forming ability of spray-dried amorphous two- and three-component composite
      particles. Particles of lactose alone, two-component particles of lactose and
      PVP, and three-component particles of lactose, PVP and a small amount of
      polysorbate 80 were prepared by spray-drying. Two qualities of PVP with different
      molecular weights were used for the preparation of both types of particles. The
      particles were characterised with respect to permeametry surface area, moisture
      content, particle and bulk density, glass transition and crystallisation
      temperature, and heat of crystallisation. The tablet tensile strength of the
      different particles formed at a series of applied pressures was determined and
      compression parameters were derived from the Heckel and Kawakita equations. The
      presence of PVP gave particles that were less prone to deform permanently during
      compression while the presence of surfactant gave particles that were less able
      to form tablets. In conclusion, the compression behaviour and tablet-forming
      ability of spray-dried amorphous lactose can be modulated by the addition of
      stabilising polymers or surfactants to the spray feed solution.

PMID- 15158905
TI  - Bioavailability of carbamazepine:beta-cyclodextrin complex in beagle dogs from
      hydroxypropylmethylcellulose matrix tablets.
AB  - The bioavailability of a carbamazepine:beta-cyclodextrin (CBZ:betaCD) complex
      from hydroxypropylmethylcellulose (HPMC) matrix tablets was evaluated in beagle
      dogs. A solubility study demonstrated the improvement of CBZ aqueous solubility
      by adding increasing amounts of betaCD. The 1:1 CBZ:betaCD molar ratio was chosen
      to produce the complex, which was obtained by spray-drying. Matrix tablets were
      prepared by direct compressing either a CBZ:betaCD complex or a physical mixture
      of both substances with HPMC. Both matrix formulations displayed a controlled
      release profile when compared to the reference formulation (Tegretol CR 200). CBZ
      presented a significantly higher bioavailability from matrix tablets containing
      the CBZ:betaCD complex than that obtained from Tegretol CR 200). Although a high
      inter-subject variability was observed, the results pointed to the feasibility of
      using betaCD in order to modulate CBZ release and absorption, as well as to
      reduce the drug dosage maintaining the same plasma levels.

PMID- 15158906
TI  - Pharmacokinetic interactions between phenylpropanolamine, caffeine and
      chlorpheniramine in rats.
AB  - As the mechanism involved in the serious adverse effects associated with
      phenylpropanolamine (PPA) has not yet been clarified, and as PPA in usual cases
      is not being ingested without other drugs combination, the aim of this study was
      to characterize the possibility of pharmacokinetic interactions between PPA and
      most often combined drugs existing in the same dosage. The pharmacokinetics of
      PPA in rat brain and blood were evaluated when administered alone (group I),
      combined with caffeine (group II), combined with chlorpheniramine (group III),
      combined with both caffeine and chlorpheniramine (group IV) and finally when
      existed in one of the available OTC products (group V). This product contains
      multiple ingredients of PPA, caffeine and chlorpheniramine. In brain the
      pharmacokinetic parameters of PPA were significantly affected with the combined
      administration of caffeine and/or chlorpheniramine. The single intraperitoneal
      administration of caffeine (5 mg/kg) with PPA (2.5 mg/kg) to rats caused 1.6-fold
      increase in the AUC of PPA in brain compared to the single administration of PPA,
      and was comparable to the 1.5-fold increase caused by chlorpheniramine (0.4
      mg/kg). The multiple combinations caused an increase in the AUC by 1.9-fold,
      which is comparable to the increase in the AUC of PPA obtained from the OTC
      product (2.2-fold). On the other hand, there was no significant difference in the
      pharmacokinetics of PPA in blood between the groups except for the C(max) of PPA
      in groups I and IV. The observed adverse effects associated with PPA use could be
      related to the significant increase in its levels in the brain.

PMID- 15158907
TI  - The prion-like protein Doppel fails to interact with itself, the prion protein
      and the 37 kDa/67 kDa laminin receptor in the yeast two-hybrid system.
AB  - The prion-like protein termed Doppel (Dpl) shows approx. 25% sequence identity
      with all known prion proteins (PrP). We recently showed that the cellular PrP is
      dimeric under native conditions, a finding which was confirmed by the
      investigation of its crystal structure. Human PrP further interacts with its
      cellular receptor, the 37 kDa/67 kDa laminin receptor (LRP/LR). Here we report
      that human Doppel fails to interact with (i). itself, (ii). the human 37 kDa/67
      kDa LRP/LR, and (iii). the human cellular prion protein (huPrP) in the yeast two
      hybrid system. Our findings suggest that Dpl and PrP are not related or are only
      marginally related with respect to their ligand binding behaviour.

PMID- 15158908
TI  - High concentrations of magnesium modulate vascular endothelial cell behaviour in
      vitro.
AB  - Magnesium supplementation has been reported to prevent cardiovascular diseases
      through the decrease of plasma lipids and to improve endothelial function in
      patients with coronary artery disease. In the present work, we evaluated whether
      high magnesium concentrations can directly affect the function of cultured
      endothelial cells, which play a crucial role in maintaining the functional
      integrity of the vascular wall. We cultured human umbilical vein endothelial
      cells for various times in media containing different concentration of magnesium
      (range 2 to 10 mM) and compared them to the corresponding controls (1 mM Mg).
      High Mg concentrations stimulated endothelial proliferation, enhanced the
      motogenic response to angiogenic factors and attenuated the response to
      lipopolysaccharide (LPS). In addition, we demonstrate that high concentrations of
      magnesium did not modulate the levels of plasminogen activator inhibitor-1, but
      enhanced the synthesis of nitric oxide, in part through the up-regulation of
      endothelial nitric oxide synthase. Our results demonstrate a direct role of
      magnesium in maintaining endothelial function. We therefore anticipate that
      magnesium may have a protective effect against atherosclerosis and could play a
      role in promoting the growth of collateral vessels in chronic ischemia. Moreover,
      because it induces the synthesis of nitric oxide, this cation could be a helpful
      tool in hypertension as well as in preventing thrombosis.

PMID- 15158909
TI  - Low magnesium promotes endothelial cell dysfunction: implications for
      atherosclerosis, inflammation and thrombosis.
AB  - Because (i). endothelial cells are important players in cardiovascular diseases
      and (ii). Mg deficiency promotes atherosclerosis, thrombosis and hypertension, we
      evaluated whether low concentrations of Mg could directly affect endothelial
      behavior. We found that low Mg concentrations reversibly inhibit endothelial
      proliferation, and this event correlates with a marked down-regulation of the
      levels of CDC25B. The inhibition of endothelial proliferation is due to an up
      regulation of interleukin-1 (IL-1), since an antisense oligonucleotide against IL
      1 could prevent the growth inhibition observed in cells exposed to low
      concentrations of the cation. We also report the up-regulation of Vascular Cell
      Adhesion Molecule-1 (VCAM) and Plasminogen Activator Inhibitor (PAI)-1 after Mg
      deficiency. VCAM is responsible, at least in part, of the increased adhesion of
      monocytoid U937 cells to the endothelial cells grown in low magnesium. In
      addition, endothelial migratory response is severely impaired. By cDNA array, we
      identified several transcripts modulated by exposure to low Mg, some of which-c
      src, ezrin, CD9, cytohesin and zyxin-contribute to endothelial adhesion to
      substrates and migration. In conclusion, our results demonstrate a direct role of
      low magnesium in promoting endothelial dysfunction by generating a pro
      inflammatory, pro-thrombotic and pro-atherogenic environment that could play a
      role in the pathogenesis cardiovascular disease.

PMID- 15158910
TI  - The role of interleukin-10 in the regulation of the systemic inflammatory
      response following trauma-hemorrhage.
AB  - Pro-inflammatory cytokine release after shock is central in the development of
      subsequent multiple organ dysfunction syndrome. Some studies suggest that
      interleukin-10 (IL-10) is an immunosuppressive mediator after injury or sepsis,
      while others suggest that IL-10 is an important regulator of the pro-inflammatory
      response. We hypothesized that in a model of trauma and hemorrhagic shock (TH),
      IL-10 regulates pro-inflammatory cytokine activity via an autocrine effect on
      cytokine mRNA transcription in Kupffer cells early after TH. To study this, male
      C3H/HeN mice were sham-operated or subjected to TH. Plasma levels of TNF-alpha,
      IL-6 and PGE(2) were elevated following TH. A sharp peak in IL-10 levels was
      observed at 2 h after the insult. Kupffer cell (KC) depletion prior to TH reduced
      plasma IL-6, IL-10 and TNF-alpha levels, whereas treatment with anti-IL-10 after
      TH increased IL-6 and TNF-alpha levels. Kupffer cell mRNA expression for IL-6, IL
      10 and TNF-alpha was elevated in the TH group and further increased by anti-IL-10
      treatment. These findings indicate that KC-dependent IL-10 regulates the early
      systemic inflammatory response after TH. Thus, while IL-10 is an important
      mediator of immunosuppression following traumatic injury, it also is beneficial
      with regard to its ability to counter-regulate the early inflammatory response
      under such conditions.

PMID- 15158911
TI  - Products of lipid peroxidation induce missorting of the principal lysosomal
      protease in retinal pigment epithelium.
AB  - Phagocytosis of photoreceptor outer segments (OS) by retinal pigment epithelium
      (RPE) is essential for OS renewal and survival of photoreceptors. Internalized,
      oxidatively modified macromolecules perturb the lysosomal function of the RPE and
      can lead to impaired processing of photoreceptor outer segments. In this study,
      we sought to investigate the impact of intracellular accumulation of oxidatively
      damaged lipid-protein complexes on maturation and distribution of cathepsin D,
      the major lysosomal protease in the RPE. Primary cultures of human RPE cells were
      treated with copper-oxidized low density lipoprotein (LDL) and then challenged
      with serum-coated latex beads to stimulate phagocytosis. Three observations were
      noted to occur in this experimental system. First, immature forms of cathepsin D
      (52 and 46 kDa) were exclusively associated with latex-containing phagosomes.
      Second, maturation of cathepsin D was severely impaired in RPE cells loaded with
      oxidized LDL (oxLDL) prior to the phagocytic challenge. Third, pre-treatment with
      oxLDL caused sustained secretion of pro-cathepsin D and the latent form of
      gelatinase A into the extracellular space in a dose-dependent manner. These data
      stimulate the hypothesis that intracellular accumulation of poorly degradable,
      oxidized lipid-protein cross-links, may alter the turnover of cathepsin D,
      causing its mistargeting into the extracellular space together with the enhanced
      secretion of a gelatinase.

PMID- 15158912
TI  - H3 mRNA level as a new proliferative marker in astrocytomas.
AB  - Replication-dependent H3.1 and H3.2 histones are encoded by 11 genes. The H3 mRNA
      levels in brain astrocytomas using real-time RT-PCR assay was examined. The
      sequence of primers and probe used in amplification was designed basing on the
      reference sequence GenBank accession no. The H3 mRNA levels correlated with tumor
      grade (R=0.56, P=0.0012), Ki-67 proliferative antigen labeling index (R=0.58,
      P=0.0008) and patient survival time (R=-0.50, P=0.005), discriminating low-grade
      and high-grade tumors. Quantification of H3 mRNA with real-time RT-PCR using the
      proposed pair of primers may supplement classic proliferative tests and
      predictive factors in brain astrocytomas.

PMID- 15158913
TI  - Two novel missense mutations in ABCA1 result in altered trafficking and cause
      severe autosomal recessive HDL deficiency.
AB  - Extremely low concentrations of high density lipoprotein (HDL)-cholesterol and
      apolipoprotein (apo) AI are features of Tangier disease caused by autosomal
      recessive mutations in ATP-binding cassette transporter A1 (ABCA1). Less
      deleterious, but dominantly inherited mutations cause HDL deficiency. We
      investigated causes of severe HDL deficiency in a 42-year-old female with
      progressive coronary disease. ApoAI-mediated efflux of cholesterol from the
      proband's fibroblasts was less than 10% of normal and nucleotide sequencing
      revealed inheritance of two novel mutations in ABCAI, V1704D and L1379F. ABCA1
      mRNA was approximately 3-fold higher in the proband's cells than in control
      cells; preincubation with cholesterol increased it 5-fold in control and 8-fold
      in the proband's cells, but similar amounts of ABCA1 protein were present in
      control and mutant cells. When transiently transfected into HEK293 cells,
      confocal microscopy revealed that both mutant proteins were retained in the
      endoplasmic reticulum, while wild-type ABCA1 was located at the plasma membrane.
      Severe HDL deficiency in the proband was caused by two novel autosomal recessive
      mutations in ABCA1, one (V1704D) predicted to lie in a transmembrane segment and
      the other (L1379F) in a large extracellular loop. Both mutations prevent normal
      trafficking of ABCA1, thereby explaining their inability to mediate apoA1
      dependent lipid efflux.

PMID- 15158914
TI  - Splicing alterations in human renal allografts: detection of a new splice variant
      of protein kinase Par1/Emk1 whose expression is associated with an increase of
      inflammation in protocol biopsies of transplanted patients.
AB  - Protein kinase Emk1/Par1 (GenBank accession no. X97630) has been identified as a
      regulator of the immune system homeostasis. Since immunological factors are
      critical for the development of chronic allograft nephropathy (CAN), we reasoned
      that expression of Par1/Emk1 could be altered in kidney allografts undergoing
      CAN. In this paper, we have analysed the association among renal allograft
      lesions and expression of Par1/Emk1, studied by RT-PCR on total RNA from 51
      protocol biopsies of transplanted kidneys, five normal kidneys, and five
      dysfunctional allografts. The most significant result obtained has been the
      detection of alterations in the normal pattern of alternative splicing of the
      Par1/Emk1 transcript, alterations that included loss of expression of
      constitutively expressed isoforms, and the inclusion of a cryptic exon to
      generate a new Emk1 isoform (Emk1C). Expression of Emk1C was associated with an
      increase in the extension of the interstitial infiltrate (0.88+/-0.33 in
      Emk1C([+]) vs. 0.41+/-0.50 in Emk1C([-]); P<0.011), and with a trend to display
      higher interstitial scarring (0.66+/-0.70 vs. 0.29+/-0.52; P=0.09) in protocol
      biopsies when evaluated according to the Banff schema. Moreover, a higher mean
      arterial pressure (MAP) was also observed (110+/-11 vs. 99+/-11 mm Hg; P=0.012).
      From these results we propose that Par1/Emk1 could have a role in the development
      of CAN in kidney allografts.

PMID- 15158915
TI  - Identification of hepatic molecular mechanisms of action of alpha-tocopherol
      using global gene expression profile analysis in rats.
AB  - The recent discovery that vitamin E (VE) regulates gene activity at the
      transcriptional level indicates that VE may exert part of its biological effects
      by mechanisms which may be independent of its well-recognised antioxidant
      function. The objective of this study was the identification of hepatic vitamin E
      sensitive genes and examination of the effects of VE on their corresponding
      biological endpoints. Two groups of male rats were randomly assigned to either a
      VE-sufficient diet or to a control diet deficient in VE for 290 days. High
      density oligonucleotide microarrays comprising over 7000 genes were used to
      assess the transcriptional response of the liver. Differential gene expression
      was monitored over a period of 9 months, at four different time-points, and rats
      were individually profiled. This experimental strategy identified several VE
      sensitive genes, which were chronically altered by dietary VE. VE supplementation
      down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid
      reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase
      was significantly up-regulated. Measurement of the corresponding biological
      endpoints such as activated partial thromboplastin time, plasma
      dihydrotestosterone and hepatic glutathione substantiated the gene chip data
      which indicated that dietary VE plays an important role in a range of metabolic
      processes within the liver.

PMID- 15158916
TI  - Air pollutants increase gene expression of the vasoconstrictor endothelin-1 in
      the lungs.
AB  - Inhalation of urban pollutants elevates the circulating levels of the vasoactive
      peptides endothelin (ET)-1 and ET-3 in rats. This effect could explain the
      association between episodic variations of urban pollutants and acute
      cardiopulmonary morbidity and mortality documented in epidemiological studies.
      Because the lungs are the primary source of circulating ET-1 and the main site of
      clearance from circulation, we investigated the response of endothelin system
      genes in the lungs of Fischer-344 rats after 4-h nose-only inhalation of 0.8 ppm
      ozone plus 49 mg/m(3) EHC-93 (Ottawa particles). The mRNA levels for preproET-1,
      preproET-3, endothelin-converting enzyme (ECE)-1, and ET receptor subtypes A and
      B were determined at 2 h, and 1, 2, 3, 7, and 14 days after exposure. The
      pollutants induced preproET-1 and ECE-1 (P<0.05) after 2 h, consistent with the
      notion of increased synthesis and conversion of the peptide ET-1 in lung
      endothelial cells. PreproET-3 mRNA was down-regulated at 2 h post-exposure
      (P<0.05), and returned to control levels by 24 h, indicating that induction of ET
      3 in the lungs is not responsible for the sustained elevation of ET-3 in plasma
      reported after inhalation of pollutants. Our results indicate that lung
      endothelin system genes respond rapidly and transiently to inhalation of urban
      pollutants, consistent with the dynamics of urban pollutant health effects in the
      human population.

PMID- 15158917
TI  - Calcium phosphate and calcium oxalate crystal handling is dependent upon CLC-5
      expression in mouse collecting duct cells.
AB  - Defects in an intracellular chloride channel CLC-5 cause Dent's disease, an
      inherited kidney stone disorder. Using a collecting duct model, mIMCD-3 cells, we
      show expression of dimeric mCLC-5. Transient transfection of antisense CLC-5
      reduces CLC-5 protein expression. Binding of both calcium phosphate
      (hydroxyapatite) and calcium oxalate monohydrate (COM) crystals overlaid onto
      mIMCD-3 cultures was affected by altered CLC-5 expression. Calcium phosphate
      crystal agglomerations (>10 microm) were minimal in control (9%) and sense (13%)
      CLC-5-transfected cells, compared to 66% of antisense CLC-5-transfected cells
      (P<0.001). Small calcium phosphate crystals (<10 microm) were found associated
      with 45% of sense CLC-5-treated cells, of which the majority (11/14 cells)
      appeared to be internalised within the cell. Calcium oxalate agglomerations (>10
      microm) were also largely absent for controls or sense mCLC-5 transfectants (11%
      and 9% of cells, respectively) with COM crystal agglomerates predominating in
      antisense CLC-5 transfectants (66%, P<0.0001). We conclude that collecting duct
      cells with reduced CLC-5 expression lead to a tendency to form calcium crystal
      agglomeration, which may help explain the nephrocalcinosis and nephrolithiasis
      seen in Dent's disease.

PMID- 15158918
TI  - Mental disorders in a forensic sample of sexual offenders.
AB  - OBJECTIVE: - The present study examined the prevalence of DSM IV axis I disorders
      and DSM IV personality disorders among sexual offenders in Forensic State
      Hospitals in Germany. METHOD: - Current and lifetime prevalence rates of mental
      disorders were investigated based on clinical structured interviews among sexual
      offenders (n = 55). Additionally, subgroups were analyzed on the basis of
      diagnostic research criteria, with 30 sexual offenders classified as paraphiliacs
      and 25 sexual offenders as having an impulse control disorder (without
      paraphilia). RESULTS: - Anxiety disorders, mood disorders, and substance use
      disorders were common among sexual offenders, as were cluster B and cluster C
      personality disorders. While social phobia was most common among paraphilic
      sexual offenders, major depression was most prevalent in impulse control
      disordered sexual offenders. CONCLUSION: - The results replicate recent findings
      of high psychiatric morbidity in sexual offenders placed in forensic facilities.
      Furthermore, differential patterns of co-morbid mental disorders were found in
      paraphiliacs and impulse control disordered sexual offenders. With regard to an
      effective therapy and relapse prevention co-morbid mental disorders should be a
      greater focus in the assessment of subgroups of sexual offenders.

PMID- 15158919
TI  - Personality trait risk factors for attempted suicide among young women with
      eating disorders.
AB  - OBJECTIVE: - Clinical observations and a review of the literature led us to
      hypothesize that certain personality and character traits could provide improved
      understanding, and thus improved prevention, of suicidal behaviour among young
      women with eating disorders. METHOD: - The clinical group consisted of 152 women
      aged between 18 and 24 years, with DSM-IV anorexia nervosa/restrictive type (AN-R
      = 66), anorexia nervosa/purging type (AN-P = 37), bulimia nervosa/non-purging
      type (BN-NP = 9), or bulimia nervosa/purging type (BN-P = 40). The control group
      consisted of 140 subjects. The assessment measures were the Minnesota Multiphasic
      Personality Inventory-second version (MMPI-2) scales and subscales, the Beck
      Depression Inventory (BDI) used to control for current depressive symptoms, plus
      a specific questionnaire concerning suicide attempts. RESULTS: - Suicide attempts
      were most frequent in subjects with purging behaviour (30.0% for BN-P and 29.7%
      for AN-P). Those attempting suicide among subjects with eating disorders were
      mostly students (67.8%). For women with AN-R the scales for 'Depression' and
      'Antisocial practices' represented significant suicidal risk, for women with AN-P
      the scales for 'Hysteria', 'Psychopathic deviate', 'Shyness/Self-consciousness',
      'Antisocial Practices', 'Obsessiveness' and 'Low self-esteem' were risk
      indicators and for women with BN-P the 'Psychasthenia', 'Anger' and 'Fears'
      scales were risk indicators. CONCLUSION: - This study provides interesting
      results concerning the personality traits of young women with both eating
      disorders and suicidal behaviour. Students and those with purging behaviour are
      most at risk. Young women should be given more attention with regard to the risk
      of suicide attempts if they: (a). have AN-R with a tendency to self-punishment
      and antisocial conduct, (b). have AN-P with multiple physical complaints, are not
      at ease in social situations and have antisocial behaviour, or (c). if they have
      BN-P and tend to be easily angered with obsessive behaviour and phobic worries.
      The MMPI-2 is an interesting assessment method for the study of traits indicating
      a risk of suicidal behaviour in young subjects, after controlling for current
      depressive pathology.

PMID- 15158920
TI  - Attempted suicide and psychiatric consultation.
AB  - This study investigated the differences in clinical characteristics between
      suicide attempters referred or not referred to psychiatric consultation after a
      suicide attempt and factors affecting such referral to psychiatric aftercare
      after attempted suicide. All 1198 consecutive suicide attempters treated in
      hospital emergency rooms in Helsinki during a 12-month period were identified.
      Data were gathered on any psychiatric consultation after the attempt and on all
      health care contacts 1 year before and after the index attempt. We found that
      half of the suicide attempters who were not referred to psychiatric consultation
      were without any aftercare recommendation and treatment contact soon after their
      attempt. Factors predicting referral to psychiatric consultation were age,
      psychotic disorder, lack of substance use disorder and, most strongly, the
      hospital where the suicide attempt was treated. Although the characteristics of a
      patient attempting suicide do play a role in determining whether a psychiatric
      consultation will take place or not, the most important factor is the
      consultation practices of the particular hospital. This in turn influences the
      probability of adequate aftercare.

PMID- 15158921
TI  - Preventing human rights abuses in psychiatric establishments: the work of the
      CPT.
AB  - The mission of the European Committee for the prevention of torture and inhuman
      or degrading treatment or punishment (CPT) is to visit all places where people
      are detained and deprived of their liberty by a public authority, in States which
      are signatories to the Convention. Within this context, the CPT has visited many
      closed psychiatric establishments. We have studied reports, which were made
      public concerning 78 psychiatric establishments visited by the CPT between 1990
      and 2001. No act considered to be torture was reported by the CPT, but several
      cases of deliberate ill-treatment of patients are described. Many serious cases
      of dysfunction concerning staff, treatment, the use of seclusion and restraint as
      well as lack of adequate safeguards, were also noted by the CPT. The
      recommendations, comments and requests for information issued by the CPT are
      intended to promote the reform of these establishments in order to promote human
      rights, in the States visited. These recommendations as well as the CPT's annual
      reports, serve as reference standards for psychiatric practice, which respect
      human rights.

PMID- 15158922
TI  - Attitudes concerning involuntary treatment of mania: results of a survey within
      self-help organizations.
AB  - PURPOSE: - The objective of the study was to determine the level of involuntary
      treatment that mood disorder patients and their families wish in the event of a
      manic or hypomanic episode. METHOD: - A survey was conducted within two self-help
      organizations during two conventions gathering over 500 patients, along with
      families and caregivers. A clinical vignette depicting an uncollaborative
      hypomanic patient beginning to endanger his professional and financial situation
      and to put undue stress upon his family was presented and followed by an eight
      item questionnaire. The level of coercive treatment seen as appropriate was
      measured by visual analogue scales. RESULTS: - The 503 respondents disagreed
      partially with the statement that the patient should decide by himself about his
      hospitalization and partially favored some involuntary treatment over treatment
      refusal. There was no difference between patients, relatives and caregivers
      related to acceptance of coercive hospitalization and treatment. Respondents
      assigned a major role to treating teams and family members in decisions for
      coercive treatment. CONCLUSION: - Most respondents (including a majority of
      patients) support a moderate degree of coercive treatment in the event of a
      hypomanic or manic state. Surveys of opinions from concerned people could
      influence, practice, legislation and possibly advance directives that could be
      written by patients or patients organizations.

PMID- 15158923
TI  - Neurological soft signs and dermatoglyphic anomalies in twins with schizophrenia.
AB  - Schizophrenia is associated with altered neural development. We assessed
      neurological soft signs (NSS) and dermatoglyphic anomalies (total a-b ridge count
      (TABRC) and total finger ridge count) in 15 pairs of twins concordant and
      discordant for schizophrenia. Within-pair differences in both NSS and TABRC
      scores were significantly greater in discordant compared to concordant
      monozygotic pairs. There was no significant difference in NSS and TABRC scores
      between subjects with schizophrenia and their co-twins without the illness.
      However, monozygotic discordant twins with schizophrenia had higher ABRCs on
      their right hands compared to their co-twins without the illness. These findings
      suggest that an unidentified environmental event acting between weeks 6 and 15 of
      gestation affects the development of monozygotic twins who go on to develop
      schizophrenia but does not have a corresponding effect on their co-twins who do
      not develop the illness. The effect of such an event on dermatoglyphic profiles
      appears lateralised to the right hand in affected twins.

PMID- 15158924
TI  - Psychiatric morbidity, disability and service use amongst primary care attenders
      in France.
AB  - Attenders (n = 124, response rate 84%) of five GPs in Montpellier completed
      questionnaires on health (reason for visit, cause of problem, GHQ-12), disability
      (WHODAS II) and service use (CSRI). For each patient, the GP filled in a brief
      form including a rating of severity of physical and psychological illness.
      Overall 30.6% of patients were classified as GHQ cases indicating probable non
      psychotic psychiatric morbidity and 58.9% were rated as having a physical illness
      by the GP. Patients with psychiatric morbidity showed as high levels of
      disability as those with a physical illness, with however a greater number of
      domains of life affected. They also had a greatly increased number of disability
      days and used services to a greater extent than those without psychiatric
      morbidity, these links being stronger than with physical illness. Use of the
      WHODAS II and the CSRI has not been previously reported in France. This study
      shows that they could be useful instruments for depicting disability and service
      use in general practice. The findings from this initial study indicate the need
      for greater research in primary care focusing on accurate detection and treatment
      of patients so that disability and excess service use associated with psychiatric
      morbidity might be reduced.

PMID- 15158925
TI  - Pathways to psychiatric care and reform of the public health care system in
      Poland.
AB  - OBJECTIVE: - Since 01.01.1999 a reform of the health care system in Poland has
      been realised based on the general health insurance act. We attempt to use the
      pathway method, especially measuring of time intervals along pathways, as a way
      of making accessibility to mental health services operational. METHOD: - In a
      period of 2 months all patients aged 15 and over who had not sought care from any
      public or private psychiatric service during the previous 365 days, were
      interviewed by psychiatrists, using the Polish version of the WHO Encounter Form.
      RESULTS: - A total of 228 patients were seen. The study reveals that the median
      interval between first seeing a primary care giver and arrival at a mental health
      service was 12 weeks, which is much longer than all other European centres in
      previous studies. CONCLUSION: - Making use of the pathway method and, in
      particular, median interval analysis between the onset of the mental health
      problem and seeing mental health professionals (MHPs) has shown practically
      limited access of patients, with a new episode of care to psychiatric services in
      both epidemiological catchment areas. This method seems to be a simple and
      inexpensive way of monitoring the accessibility to MHP in the period of health
      care reform.

PMID- 15158926
TI  - Quality of life in schizophrenics with and without the deficit syndrome.
AB  - We investigated the relations between deficit as part of schizophrenic
      symptomatology and the popular but unclear concept of quality of life (QOL). In a
      47-patient sample, subjective QOL was compared in schizophrenics with and without
      the deficit syndrome. Self- and hetero-rated QOL is more impaired in deficit
      patients. Differences between deficit and non-deficit groups are more significant
      as the index used for measuring QOL gets less "behavioral" and more "psycho
      pathological". These results are consistent with existing literature. The
      "behavioral" dimensions of Heinrichs' quality of life scale (QLS) are less
      discriminative between deficit and non-deficit schizophrenics, but they are more
      independent of the symptoms. They might have a special clinical meaning, which
      needs to be defined. The concepts of QOL (as used in QLS) and deficit
      symptomatology are partially redundant. QLS might be an inappropriate, or at
      least un-specific measure of QOL.

PMID- 15158927
TI  - Mania and hypomania with olanzapine use.

PMID- 15158928
TI  - Clozapine treatment of a borderline personality disorder with severe self
      mutilating behaviours.

PMID- 15158929
TI  - Duplication 15q14 --> pter: a rare chromosomal abnormality underlying bipolar
      affective disorder.
AB  - We have followed up a patient with 8q24.2 --> qter and 15q14 --> pter duplication
      due to a maternal reciprocal translocation, a condition related to Prader-Willi
      Syndrome. Apart from dysmorphic features, the patient suffered from recurring
      episodes of bipolar psychosis. Interestingly, PET scanning revealed revealed
      prominent bilateral hypometabolism in the frontal, temporal, and parietal lobes
      as well as in the cerebellum. Possible implications of this rare chromosomal
      abnormality with regards to psychiatric disorders are discussed, with emphasis on
      recent evidence suggesting chromosome 15q13-15 as a susceptibility locus for
      psychosis.

PMID- 15158930
TI  - DSM-IV mental disorders and neurological complications in children and
      adolescents with human immunodeficiency virus type 1 infection (HIV-1).
AB  - AIM: - To study the types of psychiatric problem encountered in children infected
      with the human immunodeficiency virus (HIV) and their relationship to central
      nervous system disorder and the severity of infection. METHODS: - 17 HIV-infected
      children presenting with psychiatric problems were included. Mental disorders
      were evaluated according to DSM-IV criteria. Neurological disorders and
      progressive encephalopathy (presence or absence) diagnosis were evaluated by
      clinical and radiological examination. The severity of infection was assessed by
      the percentage of CD4 lymphocytes. RESULTS: - The most frequent diagnoses were
      major depression (MDD: 47%) and attention deficit hyperactivity disorder (ADHD:
      29%). Major depression diagnosis was significantly associated with neuroimaging
      or clinical neurological abnormalities (p < 0.01). In contrast, no association
      was found between hyperactivity diagnosed according to DSM-IV criteria and
      central nervous system disorder. Percentage of CD4 lymphocytes were close to 0
      for more than 80% of children presenting with psychiatric complications.
      CONCLUSION: - The very low % of CD4 lymphocytes of these children suggest that
      the appearance of a psychiatric complication should be regarded as a factor
      indicating severe HIV infection. Depressive disorders may be a clinical form of
      encephalopathy.

PMID- 15158931
TI  - Adjunctive citalopram is effective on hallucinations and depersonalization
      symptoms: a case report.

PMID- 15158932
TI  - Microbubble contrast agents for echocardiography: rationale, composition,
      ultrasound interactions, and safety.
AB  - Imaging the small blood vessels within the myocardium, which contains only a
      small fraction of the total coronary blood volume, is a significant challenge for
      ultrasound imaging. Recent advances in microbubble design and ultrasound
      technology have improved our ability to image the microcirculation. It is
      essential to understand the fundamentals of microbubble behavior in an ultrasound
      field and how it impacts technology and safety.

PMID- 15158933
TI  - Imaging technologies and techniques.
AB  - Equipment manufacturers provide contrast-specific detection techniques that have
      excellent sensitivity and excellent agent-to-tissue specificity along with
      helpful tools that improve workflow efficiency dramatically. Excellent contrast
      agents have been approved for LV opacification and are available worldwide.
      Techniques designed for low-MI imaging offer real-time acquisition capabilities
      and lead to faster examinations. Techniques designed for medium-MI imaging offer
      better sensitivity than low-MI techniques while maintaining the benefit of rapid
      image acquisition. Techniques designed for high-MI imaging offer the best
      sensitivity with longer acquisition times. These techniques are viable means for
      imaging contrast agents tailored to clinical needs. Progress by contrast agent
      manufacturers, equipment manufacturers, and physicians will continue to drive
      improvements in the areas of detection and clinical workflow for improved patient
      care.

PMID- 15158934
TI  - Implementing contrast echocardiography in the laboratory.
AB  - Contrast echocardiography is an important and a significant addition to a modern
      echocardiography laboratory. Its successful implementation is dependent on a team
      approach between sonographers, nurses, and physicians. A practical plan is one
      that includes a proper understanding of indications, logistical matters,
      technical and performance standards, and reimbursement issues.

PMID- 15158935
TI  - Assessment of left ventricular function with contrast echocardiography.
AB  - Echocardiography continues to be the primary noninvasive imaging modality for the
      assessment of cardiac structure and function because of significant advances in
      ultrasound imaging technology over the last two decades, yet quantification of
      the LV function has remained an elusive goal. The introduction of contrast agents
      has represented a major advance in clinicians' ability to visualize the
      endocardium and to assess LV function accurately, particularly in patients who
      have poor acoustic windows. Ongoing and future refinements in imaging technology
      used with contrast enhancement have placed automated quantification of LV
      function on the brink of widespread clinical use.

PMID- 15158936
TI  - The coronary microcirculation in health and disease.
AB  - Apart from being the site of nutrient and gas exchange for the myocardium, the
      capillary bed is a dynamic participant in the regulation of coronary and
      myocardial blood flow. MBV also responds to changes in myocardial oxygen demand.
      Because MCE can be used to assess MBF and MBV in vivo, it can be used to provide
      unique insights into tissue perfusion.

PMID- 15158938
TI  - Myocardial contrast echocardiography in acute coronary syndromes.
AB  - MCE is a reliable, bedside technique for assessment of a patient with acute
      coronary syndrome. It can be used to estimate the myocardial risk-area and
      infarct size and to establish peri-infarct viability. This information is
      critical in both management decision-making and in assigning prognosis in the
      setting of acute coronary syndromes.

PMID- 15158937
TI  - Myocardial contrast echocardiography in the detection of coronary stenosis.
AB  - The need for the capillary bed to maintain normal hydrostatic pressure results in
      capillary derecruitment distal to a stenosis during hyperemia. This
      pathophysiologic behavior is seen irrespective of the method by which coronary
      driving pressure is reduced. The functional consequences of the decrease in MBV
      are an increase in myocardial vascular resistance and a concomitant reduction in
      hyperemic MBF. These phenomena form the basis for the detection of CAD with MCE,
      which isa unique noninvasive tool that allows the separate assessment of both MBV
      and MBF velocity. Because of its excellent spatial and temporal resolution,
      portability, widespread availability,and relatively low cost, MCE should provide
      an attractive method for the noninvasive detection of CAD and for the
      quantification of stenosis severity.

PMID- 15158939
TI  - Myocardial contrast echocardiography in chronic ischemic and nonischemic
      cardiomyopathies.
AB  - The coronary microcirculation is integral in the pathophysiology of both ischemic
      and non-ischemic cardiomyopathies. MCE is a unique tool for studying
      microcirculatory integrity, not only to aid diagnosis and determination of
      prognosis but also to guide interventions and management. The expanding paradigm
      of microcirculatory disturbances may in the future also include hypertensive and
      diabetic heart disease.

PMID- 15158940
TI  - Targeted ultrasound imaging using microbubbles.
AB  - Targeted ultrasound imaging uses acoustically active contrast agents bearing a
      ligand on the surface that binds to a function-specific molecule. These
      ultrasound contrast agents are typically gas-filled microbubbles, nongaseous
      liposomes, or lipid-encapsulated perfluorocarbon emulsions. Binding of the
      contrast agent to the target results in persistent contrast enhancement during
      ultrasound imaging. This approach has been applied to the ultrasound imaging of
      pathophysiologic processes such as inflammation associated with ischemia
      reperfusion, heart transplant rejection, atherosclerotic plaque, thrombus, and
      apoptosis.

PMID- 15158941
TI  - Drug and gene delivery and enhancement of thrombolysis using ultrasound and
      microbubbles.
AB  - This article reviews some important characteristics of microbubbles that give
      them therapeutic properties. It discusses the use of microbubbles and ultrasound
      for targeted delivery of adenovirus and nonviral vectors to myocytes and
      endothelial cells and for the dissolution of thrombus or potentiation of
      fibrinolytic agents for acutely thrombosed vessels. Potential applications, such
      as induction of angiogenesis, inhibition of neointimal hyperplasia, and in the
      setting of acute myocardial infarction and ischemic stroke,are discussed briefly.

PMID- 15158942
TI  - Contrast for vascular imaging.
AB  - This article discusses the use of standard contrast agents that, when coupled
      with high-resolution carotid ultrasound, offers the dramatic potential to improve
      measurement of intimal medial thickness, better defining luminal endothelial
      surface, improving the determination of plaque ulceration, and offering the
      dramatic capabilities to visualize directly neovasculature growth of the vasa
      vasorum. The technique may identify vulnerable plaques and may also show their
      alterations with therapeutic pharmacologic interventions. In the coronary
      circulation, use of contrast significantly enhances the ability to image the
      epicardial coronary arteries to obtain data on coronary flow reserve for the
      diagnosis of coronary artery disease.

PMID- 15158945
TI  - Poly-epsilon-caprolactone microspheres and nanospheres: an overview.
AB  - Poly-epsilon-caprolactone (PCL) is a biodegradable, biocompatible and
      semicrystalline polymer having a very low glass transition temperature. Due to
      its slow degradation, PCL is ideally suitable for long-term delivery extending
      over a period of more than one year. This has led to its application in the
      preparation of different delivery systems in the form of microspheres,
      nanospheres and implants. Various categories of drugs have been encapsulated in
      PCL for targeted drug delivery and for controlled drug release. Microspheres of
      PCL either alone or of PCL copolymers have been prepared to obtain the drug
      release characteristics. This article reviews the advancements made in PCL-based
      microspheres and nanospheres with special reference to the method of preparation
      of these and their suitability in developing effective delivery systems.

PMID- 15158946
TI  - Hemolysate-filled polyethyleneimine and polyurea microcapsules as potential red
      blood cell substitutes: effect of aqueous monomer type on properties of the
      prepared microcapsules.
AB  - In this paper, we describe the synthesis and characterization of rabbit
      hemolysate-filled polyethyleneimine (PEI)- or polyurea (PU)-type artificial red
      blood cells (ARBCs) with different membrane compositions. These microcapsules
      were prepared by making use of the interfacial polymerization (IP) reaction
      between the water-soluble amine monomers (triethylamine (TEA), ethylene glycol
      bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGATA), diethylenetriamine
      (DETA), tetramethyl diaminomethane (TMDAM), piperazine hexahydrate (PPHH), l
      lysine monohydrochloride (LLMH) or PEI) and 2,4-toluylene diisocyanate (TDI) as
      an oil-soluble shell monomer. The resultant microcapsules were spherical and with
      mean diameters of 8.71-63.33 microm. Microcapsules having sulfonic acid groups on
      their surfaces were prepared by using a combination of the functional amines
      (DETA, LLMH or PEI) and 4,4'-diaminostilbene-2,2'-disulfonic acid (DASSA). Oxygen
      binding abilities of the ARBCs were measured by a Clark-type oxygen electrode.
      The obtained results revealed that the highest oxygen-binding abilities were
      obtained with the PU-ARBCs prepared with DETA alone or in combination with EGATA.
      Unfortunately, these microcapsules exhibited large diameters and wider size
      distribution curves (span values (S) = 1.3, 1.7, geometric standard deviation
      sigma(g) = 1.85, 2.18, respectively). However, the novel ARBCs (sulfonated PU-PEI
      graft copolymer membrane microcapsules (SPU/PEI-ARBCs)) prepared had good oxygen
      affinity, the smallest mean diameter (d = 8.71 microm) and the best distribution
      (S = 0.9, sigma(g) = 1.48) and a flow behavior identical to rabbit RBCs.
      Therefore, these unique microcapsules can be recommended for scale-up
      considerations as a promising blood substitute.

PMID- 15158947
TI  - Modification of physicochemical and mechanical properties of shellac by partial
      hydrolysis.
AB  - The shellac was modified by partial hydrolysis with 2.0% (w/w) NaOH for different
      times. The hydrolysed shellac was then evaluated for physicochemical and film
      properties in comparison with native shellac. The tablets coated with native and
      hydrolysed shellac were also evaluated. The results demonstrated that acid value
      (AV) of shellac increased with prolongation of hydrolysis time. The solubility of
      shellac in buffer solution (pH < or = 7) gradually increased with increasing
      hydrolysis time. The films prepared from hydrolysed shellac were more flexible
      and soft than those prepared from native shellac. The increasing of flexibility
      was correlated with the increasing of soft resin in shellac. The water vapor
      permeability of hydrolysed shellac film was lower than that of native shellac
      film. The higher acid permeability of the tablet coated with hydrolysed shellac
      was observed. In ethanol-based film coating, shellac had lower solubility and
      thus lower drug dissolution from coated tablets was observed. In ammonia-based
      film coating, the solubility of shellac was improved higher nearby pH 7.0 by an
      ammonium neutralisation method because of forming well-soluble salts, thereby
      higher drug dissolution was obtained. Partial hydrolysis provided modified
      shellac, which is more effective for ammonium salt formation, thus very higher
      drug dissolution was achieved in the ammonia-based coated tablets.

PMID- 15158948
TI  - Acetaminophen-containing chewable tablets with suppressed bitterness and improved
      oral feeling.
AB  - The aim of this study was to develop acetaminophen chewable tablets with
      suppressed bitterness and improved oral feeling by examination of hard fats as
      the matrix base and of sweetening agents as corrigents. Witepsol H-15, W-35, S
      55, E-75 and E-85, and Witocan H and 42/44 were used as hard fats. Witocan H and
      42/44 were selected in view of improved oral feeling. Witocan H/Witocan 42/44
      mixture tablets showed different melting characteristics and drug release rates
      dependent on their ratios, and those with the Witocan H/Witocan 42/44 ratio of
      92.5% (w/w) and more showed good drug release. Sucrose, xylitol, saccharin,
      saccharin sodium, aspartame and sucralose were used as sweetening agents, and
      applied alone or with Benecoat BMI-40 or cocoa powder. The Witocan H tablet with
      1% (w/w) saccharin plus 5% (w/w) Benecoat BMI-40 (Sc1-B5), and the Witocan
      H/Witocan 42/44 (92.5:7.5, w/w) mixture tablet with 1% (w/w) aspartame plus 5%
      (w/w) Benecoat BMI-40 suppressed bitterness and sweetness excellently, but the
      former tablet showed better drug release. Thus, the Witocan H tablet with Sc1-B5
      is suggested as the best acetaminophen chewable tablet, exhibiting suppressed
      bitterness, low sweetness, improved oral feeling and good drug release.

PMID- 15158949
TI  - Effect of beta-sitosterol on the characteristics of vesicular gels containing
      chlorhexidine.
AB  - Previous studies confirm that beta-sitosterol is very effective in altering the
      molecular packing of soybean lecithin bilayers even more than the cholesterol.
      The primary aim of the present study was to evaluate the influence of the beta
      sitosterol portion in the lipid bilayer on the physical-chemical characteristics
      of the prepared gel systems, and its influence on the consequent drug release
      from the liposomes obtained from vesicular phospholipid gels (VPG-s) by
      redispersion. VPG-s were prepared of different molar ratios of lecithin:sterol
      components (10:90-35:65 mol%). The mixture was hydrated with the aqueous solution
      of chlorhexidin digluconate in order to achieve 30% (w/w) final concentration of
      the lipid mixtures and 4% (w/w) concentration of the drug in each homogenized VPG
      sample. To characterize the obtained VPG systems optical microscopic examinations
      using polarized light, differential scanning calorimetry (DSC), photon
      correlation spectroscopy (PCS), and dynamic surface tension measurements were
      carried out. Vertical type diffusion cell was applied to determine the amount of
      released chlorhexidine digluconate. As a result of the surface tension-decreasing
      effect of beta-sitosterol, the membrane deformability and the dispersity of the
      system increased. The increased dispersity and fluidity significantly increased
      the extent of released chlorhexidine from the vesicles.

PMID- 15158950
TI  - Development of a controlled release formulation based on SLN and NLC for topical
      clotrimazole delivery.
AB  - Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are
      colloidal carrier systems providing controlled release profiles for many
      substances. Clotrimazole-loaded SLN and NLC were prepared by the hot high
      pressure homogenization technique in order to evaluate the physical stability of
      these particles, as well as the entrapment efficiency of this lipophilic drug and
      its in vitro release profile. The particle size was analyzed by PCS and LD
      showing that the particles remained in their colloidal state during 3 months of
      storage at 4, 20 and 40 degrees C. For all tested formulations the entrapment
      efficiency was higher than 50%. The obtained results also demonstrate the use of
      these lipid nanoparticles as modified release formulations for lipophilic drugs
      over a period of 10 h.

PMID- 15158951
TI  - Influence of cryogenic grinding on properties of a self-emulsifying formulation.
AB  - Recently, self-emulsifying drug delivery systems (SEDDS) have been developed as a
      method to deliver lipophilic drugs. Gelucire 44/14 is an excipient, from the
      lauroyl macrogolglycerides family, producing a fine oil-in-water emulsion when
      introduced into an aqueous phase under gentle agitation as SEDDS, improving
      thereby solubility of poorly water-soluble drugs and their bioavailability. The
      aims of this study were to process Gelucire 44/14 into a powder by cryogenic
      grinding to produce solid oral dosage forms and to investigate influence of this
      process on different properties of a formulation made of Gelucire 44/14 and
      ketoprofen (90/10). Cryogenic grinding produced Gelucire 44/14 in a powder form
      and this process did not change its physical properties, emulsification
      capacities and dissolution performances of the formulation tested. However,
      interactions took place between ketoprofen and Gelucire 44/14 with a decrease of
      the melting peak and a reduction of the droplet size of the formed emulsion. The
      influence of drug-Gelucire 44/14 interactions must be investigated case by case
      in any formulations.

PMID- 15158952
TI  - Evaluation of new propofol aqueous solutions for intravenous anesthesia.
AB  - The aim of this study was to evaluate the potential of using three new aqueous
      formulations of propofol for intravenous (i.v.) anesthesia. The first formulation
      can be prepared by using hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as a
      solubilizer. Phase-solubility analysis showed a linear increase in the solubility
      of propofol to a maximum of 16.6 mg/ml in 30% (w/v) HP-gamma-CD. Moreover, phase
      solubility studies demonstrated that 18% (w/v) HP-beta-CD or SBE-beta-CD and 24%
      HP-gamma-CD solutions, respectively, are required to dissolve 10mg of propofol in
      1 ml of the vehicle; the corresponding solutions, however, are slightly
      hypertonic. Autoclaving the 10 mg/ml CD-based formulations for 15 min at 121
      degrees C caused a change in pH which was more evident for the HP-beta-CD-based
      formulation while, in any case, no detectable fall in propofol concentration was
      observed. The second formulation herein evaluated is a co-solvent mixture (i.e.,
      propylene glycol:water (1:1), v/v) which is able to dissolve 10 mg/ml of the
      anesthetic agent. However, although it is simple to prepare, the stability of
      this formulation is limited. The third aqueous formulation can be prepared by
      using the prolinate ester of propofol and its water-soluble derivative dissolved
      in water at equimolar concentration. The efficacy of all these formulations as
      i.v. anesthetic agents was assessed using a pharmacodynamic measure (onset and
      duration of loss of the righting reflex, LORR), and compared with that of the
      commercial propofol formulation (Diprivan, 10 mg/ml) in rats. It was found that
      minimizing the amount of cyclodextrin in all CD-based formulations, anesthetic
      effects comparable to those of propofol in Diprivan were still observed.
      Moreover, the prolinate ester constituted an effective i.v. anesthetic
      formulation with the same duration of action but with a longer induction time
      than Diprivan.

PMID- 15158953
TI  - Characterization and drug-permeation profiles of microporous and dense cellulose
      acetate membranes: influence of plasticizer and pore forming agent.
AB  - The use of pore forming agents and plasticizers are efficient ways to obtain
      membranes for controlled drug permeation through polymeric membranes. The
      challenge of the present study was to combine these two strategies to obtain
      cellulose acetate (CA) membranes, where poly(caprolactone triol) (PCL-T) was used
      as a plasticizer and water, dissolved in a casting solution, was used as a pore
      forming agent. First, the influence of water on membrane morphology, porosity and
      the permeation coefficient of a model drug (paracetamol) was analyzed. The
      influence of different amounts of PCL-T on the permeation coefficient of the CA
      membranes was then evaluated. Finally, both strategies were combined to obtain
      porous CA/PCL-T membranes. The membrane microstructure was analyzed using
      scanning electron microscopy (SEM), the CA crystallinity was determined via
      differential scanning calorimetry (DSC), and membrane permeability was
      investigated using paracetamol. The addition of water, a non-solvent, during the
      membrane casting process was found to be a simple and effective way to change
      membrane porosity and consequently the drug-permeation profile. When small
      quantities of non-solvent were used to obtain low porosity membranes, the
      presence of a plasticizer agent could be used to better modulate drug permeation.
      Combining the addition of PCL-T with the use of a non-solvent resulted in a
      series of CA membranes with paracetamol-permeation coefficient values in the
      range of ca. 10(-7) to 10(-5) cm s(-1).

PMID- 15158954
TI  - New hypoglycaemic agents selected by molecular topology.
AB  - New compounds showing hypoglycaemic activity have been designed through a
      computer aided method based on quantitative structure-activity relationship
      (QSAR) and molecular connectivity. After calculation of topological indices for a
      set of 89 compounds including active and inactive with regards to hypoglycaemic
      action, linear discriminant analysis was performed so that a useful model to
      predict such an activity was achieved. Later on, the discriminant model was
      applied on a huge database so that fourteen compounds were selected as potential
      new hypoglycaemics. From them, just five were finally selected for experimental
      test on expected hypoglycaemic activity. Among the selected compounds, l
      arabitol, Acid blue 161, 1,4-butanediol diglycidil ether and Acid red 151 stand
      out, which are comparable in potency to standard drugs such as tolbutamide. Acid
      blue has a glycaemia profile similar to that of tolbutamide but does not lead to
      a severe hypoglycaemic condition, while the profile of the other agents is near
      normality.

PMID- 15158955
TI  - Impact of excipients on the absorption of P-glycoprotein substrates in vitro and
      in vivo.
AB  - The efflux transporter, P-glycoprotein (P-gp), located in the apical membranes of
      intestinal absorptive cells, can reduce the bioavailability of a wide range of
      orally administered drugs. A number of surfactants/excipients have been shown to
      inhibit P-gp, and thus potentially enhance drug absorption. In this study, the
      improved everted gut sac technique was used to screen excipients for their
      ability to enhance the absorption of digoxin and celiprolol in vitro. The most
      effective excipients with digoxin were (at 0.5%, w/v): Labrasol > Imwitor 742 >
      Acconon E = Softigen 767 > Cremophor EL > Miglyol > Solutol HS 15 > Sucrose
      monolaurate > Polysorbate 20 > TPGS > Polysorbate 80. With celiprolol, Cremophor
      EL and Acconon E had no effect, but transport was enhanced by Softigen 767 > TPGS
      > Imwitor 742. In vivo, the excipients changed the pharmacokinetic profile of
      orally administered digoxin or celiprolol, but without increasing the overall
      AUC. The most consistent change was an early peak of absorption, probably due to
      the higher concentration of excipient in the proximal intestine where the
      expression of P-gp is lower. These studies show that many excipients/surfactants
      can modify the pharmacokinetics of orally administered drugs that are P-gp
      substrates.

PMID- 15158956
TI  - In vitro evaluation of PLA nanoparticles containing a lipophilic drug in water
      soluble or insoluble form.
AB  - Cloricromene (AD6), an anti-ischemic drug, is rapidly metabolised into a stable
      and active metabolite (cloricromene acid, AD6-acid) poorly soluble in water and
      less lipophilic than cloricromene. The aim of this study was to evaluate which of
      the two forms has more possibility to be efficiently encapsulated in
      nanoparticles based on poly(D,L-lactide) and prepared using the nanoprecipitation
      method. Increasing the theoretical loading of AD6, an increase in drug actual
      loading and in the mean particle size occurred, while no formation of
      nanoparticles was observed when the highest theoretical loading (50 mg) was
      employed. Changing the pH of the aqueous phase the drug content dramatically
      increased. However, at a pH value of 11 a more rapid hydrolysis of AD6 occurred.
      When AD6-acid was embedded in the nanoparticles, suitable results concerning both
      drug content and encapsulation efficiency were achieved. A good control in the
      release of AD6 from the AD6-loaded nanoparticles was observed while the
      liberation of AD6-acid from the AD6-acid-loaded nanoparticles was faster than the
      dissolution of the AD6-acid free. These results confirm that the most easy
      encapsulable form in nanoparticles is AD6-acid probably owing to its poor water
      solubility. Further studies will be carried out in order to evaluate if the
      increase in the liberation of AD6-acid by nanoencapsulation may have outcomes in
      its bioavaibility in vivo.

PMID- 15158958
TI  - Milling of agglomerates in an impact mill.
AB  - Milling of agglomerates is one of the common unit operations during preparation
      of oral dosage forms like capsules and tablets. In literature the breakage of
      granules is mostly determined after single impact at an ideally formed granule or
      of single particles. In this paper the breakage behavior of agglomerates after
      milling with multiple impacts has been studied. It investigates the effects of
      the formulation and the influences of the mill settings. With respect to the
      formulation it has been found that both the size of the particles before
      granulation and the amount of binder used determine the breakage behavior. Both
      parameters have an influence on the strength of the granule to be milled, where
      initial particle size has the largest effect. A relation has been found between
      the strength of granules and the degree of size reduction. Regarding the mill
      settings, there are no mill parameters which influence the formation of fines
      independently. Formation of fines is always the result of the total degree of
      size reduction. It is not possible to achieve a large degree of size reduction
      without intensive fines formation. The results indicate that it is possible to
      achieve every desired average particle size. However, when formation of dust has
      to be reduced, multiple milling steps with separation of in-size particles is
      necessary.

PMID- 15158957
TI  - A hydroxyethylated cholesterol-based cationic lipid for DNA delivery: effect of
      conditioning.
AB  - We have synthesised a novel cholesterol-based cationic lipid to promote DNA
      transfer in cells. This lipid, dimethyl hydroxyethyl aminopropane carbamoyl
      cholesterol iodide (DMHAPC-Chol) contains a biodegradable carbamoyl linker and a
      hydroxyethyl group in the polar amino head moiety and is characterised by NMR.
      Liposomes prepared from this lipid and dioleoyl phosphatidyl ethanolamine (DOPE)
      in equimolar proportion showed a weak cytotoxicity as revealed by MTT assays and
      are efficient to deliver plasmids DNA evaluated by the expression of reporter
      genes in vitro and in vivo. In this paper, we present an original method to
      determine the lipid concentration based on the colorimetric detection of the
      colipid DOPE and the measure of the molar ratio DOPE/cationic lipid in the
      liposome by FTIR spectroscopy. The liposomes and lipid/DNA complexes structures
      were characterized by transmission electron microscopy (TEM) and by quasi-elastic
      light scattering (QLS). TEM indicated that the complexes correspond to aggregates
      containing globular substructures with liposomes size. The method of immuno-gold
      labelling was used to detect plasmid in the complex and reveals the presence of
      DNA inside the aggregates. Transfection results showed efficient DNA transfer
      depending on the charge ratio and liposomes conditioning. Gel retardation results
      indicated that at a molar charge ratio between X = 1.5 and X = 2.5 (depending on
      the liposome conditioning), all DNA was taken by liposomes. We showed that
      conditioning by freeze-drying (lyophilization) facilitates storage and improves
      transfection efficiency. When the liposomes were lyophilized prior to DNA
      addition or when the complexes were subjected to freeze-thawing cycles, the
      obtained complexes showed a transfection with levels enhanced up to four and five
      fold respectively for the lyophilized liposomes and freeze-thawed complexes. NMR
      was used to characterize the modifications under freezing which showed an effect
      on 31P spectra.

PMID- 15158959
TI  - Transdermal permeation of WIN 55,212-2 and CP 55,940 in human skin in vitro.
AB  - Synthetic cannabinoids have a promising future as treatments for nausea, appetite
      modulation, pain, and many neurological disorders. Transdermal delivery is a
      convenient and desirable dosage form for these drugs and health conditions. The
      aim of the present study was to investigate the in vitro transdermal permeation
      of two synthetic cannabinoids, WIN 55,212-2 and CP 55,940. Transdermal flux, drug
      content in the skin, and lag times were measured in split-thickness human
      abdominal skin in flow-through diffusion cells with receiver solutions of 4%
      bovine serum albumin (BSA) or 0.5% Brij 98. Differential thermal analysis (DSC)
      was performed in order to determine heats of fusion, melting points, and relative
      thermodynamic activities. The in vitro diffusion studies in 0.5% Brij 98
      indicated that WIN 55,212-2 diffuses across human skin faster than CP 55,940. The
      WIN 55,212-2 skin disposition concentration levels were also significantly higher
      than that of CP 55,940. Correspondingly, CP 55,940 was significantly metabolized
      in the skin. WIN 55,212-2 flux and skin disposition were significantly lower into
      4% BSA than into 0.5% Brij 98 receiver solutions. There was no significant
      difference in the flux, lag time, and drug content in the skin of CP 55,940 in 4%
      BSA versus 0.5% Brij 98 receiver solutions. The DSC studies showed that CP 55,940
      had a significantly lower melting point, smaller heat of fusion, and
      corresponding higher calculated thermodynamic activity than the more crystalline
      WIN 55,212-2 mesylate salt. The permeation results indicated that WIN 55,212-2
      mesylate, CP 55,940, and other potent synthetic cannabinoids with these
      physicochemical properties could be ideal candidates for the development of a
      transdermal therapeutic system.

PMID- 15158960
TI  - Surface studies on acrylic bone cement.
AB  - Poly(methyl methacrylate) (PMMA) is used to fill the gap between the prosthesis
      and the surrounding bone in cemented arthroplasties. Biocompatibility problems
      related to bone cement application limit the clinical success of these cemented
      arthroplasties. Being the cement surface in close connection with the living
      bone, it is reasonable to assume that surface properties such as, surface
      composition and surface energy, will play a role in the biomaterial performance.
      X-ray photoelectron spectroscopy (XPS) analysis and surface energy studies were
      carried out during 4 months, in order to assess a possible correlation between
      aging time and surface changes. The aging of PMMA, in a biological model fluid,
      strongly influences the composition and wettability of the cement surface. These
      changes may be explained through the hydrolysis of PMMA ester groups and the
      subsequent hydrogen bonding. Although our study does not exactly reproduce the in
      vivo environment surrounding a prosthesis, it suggests that the changes in the
      composition and wettability of the surface may modulate the host response towards
      the implant, thus contributing to its loosening.

PMID- 15158961
TI  - A novel spray-drying technique to produce low density particles for pulmonary
      delivery.
AB  - To date, all marketed DPI products rely on jet-milled, micronized drugs.
      Micronization often leads to drug powders exhibiting a large hydrophobic surface
      area resulting in strong cohesive forces, agglomeration and unsuitable
      aerosolization properties. In the current study, a new approach to prepare low
      density drug particles is described. Briefly, an oil-in-water emulsion consisting
      of an aqueous phase containing the dissolved model drug salbutamol sulphate,
      suitable surfactants, such as poloxamer or phosphatidylcholine, and optionally a
      bulking agent like lactose or a cyclodextrin derivative, and a lipid-phase that
      essentially consists of a liquefied propellant is spray-dried. By means of this
      process particles of very low density (0.02 g/cm3) and a drug load of 40% were
      prepared. The particle exhibit a porous to hollow structure, are thin-walled and
      of irregular shape. Depending on the composition of the aqueous phase, mean
      geometric particle sizes of <5 microm were obtained. It could be shown that a
      higher amount of poloxamer in the feed emulsion resulted in particles with
      improved dispersibility. Reducing the vapour pressure of the inner propellant
      phase by addition of dichloromethane decreased the agglomeration tendency of the
      powders as a result of the irregular particle morphology and, hence, resulted in
      higher fine particle fractions.

PMID- 15158962
TI  - Selected papers from the 11th International Pharmaceutical Technology Symposium.
      September 9-11, 2002. Istanbul, Turkey.

PMID- 15158963
TI  - Unmasking the dynamic interplay between efflux transporters and metabolic
      enzymes.
AB  - Drug efflux by intestinal P-glycoprotein (P-gp) is known to decrease the
      bioavailability of many CYP3A4 substrates. We have demonstrated that the
      interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase
      the opportunity for drug metabolism by determining bidirectional extraction
      ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4
      substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as
      well as two negative control, CYP3A4 only substrates, midazolam and felodipine.
      Studies were carried out under control conditions, with a P-gp inhibitor (GG918)
      and with a dual inhibitor (cyclosporine). Measurement of intracellular
      concentration changes is an important component in calculating the extraction
      ratios. We hypothesize that the inverse orientation of P-gp and CYP3A4 in the
      liver will result in an opposite interactive effect in that organ. In vivo rat
      intestinal perfusion studies with K77 and rat liver perfusion studies with
      tacrolimus under control conditions and with inhibitors of CYP3A4
      (troleandomycin), P-gp (GG918) and both CYP3A4/P-gp (cyclosporine) lend support
      to our hypotheses. These results serve as a template for predicting enzyme
      transporter (both absorptive and efflux) interactions in the intestine and the
      liver.

PMID- 15158965
TI  - Magnetically modulated therapeutic systems.
AB  - Magnetically targeted drug delivery by particulate carriers is an efficient
      method of delivering drugs to localized disease sites, such as tumors. High
      concentrations of chemotherapeutic or radiological agents can be achieved near
      the target site without any toxic effects to normal surrounding tissue. Non
      targeted applications of magnetic microspheres and nanospheres include their use
      as contrast agents (MRI) and as drug reservoirs that can be activated by a magnet
      applied outside the body. Historic and current applications of magnetic
      microspheres will be discussed, as well as future directions and problems to be
      overcome for the efficient and beneficial use of magnetic carriers in clinical
      practice. More information about the field and an extensive bibliography is
      available at "."

PMID- 15158964
TI  - Devices based on intelligent biopolymers for oral protein delivery.
AB  - The primary goal of bioadhesive controlled drug delivery is to localize a
      delivery device within the body to enhance the drug absorption process in a site
      specific manner. An important contributor to good adhesion is the presence of
      molecular adhesion promoters such as polymer-tethered structure (e.g.,
      poly(ethylene glycol) chains grafted to crosslinked networks) or even linear
      chains which are free to diffuse across the gel/gel interface. Recently, we have
      developed a very promising class of carriers for drug and especially protein
      delivery. Copolymer networks of poly(methacrylic acid) grafted with poly(ethylene
      glycol) exhibit reversible, pH-dependent swelling behavior due to the formation
      of interpolymer complexes between protonated pendant acid groups and the etheric
      groups on the graft chains. Gels containing equimolar amounts of MAA/EG exhibited
      the lowest degree of swelling at low pH increased complexation. The average
      network mesh size or correlation length was dramatically affected by the pH of
      the swelling solution. The in vitro release of insulin from P(MAA-g-EG) gels
      containing PEG grafts of molecular weight 1000 indicates a significant release of
      insulin as the gel decomplexes and insulin is freed through the structure. The
      results of additional in vitro studies have shown that insulin release rates can
      be controlled by appropriate adjustment of the structure of the gels.

PMID- 15158966
TI  - Gel and solid matrix systems for the controlled delivery of drug carrier
      associated nucleic acids.
AB  - In order to achieve a sustained pharmacological activity of oligonucleotides
      (ODNs) and avoid repeated administrations, we have developed a new concept of
      delivery system that combine sustained release and improved intracellular
      penetration. These systems are designed for the intravitreal delivery of
      antisense ODNs. The first concept consisted in using liposomes dispersed in a
      thermosensitive gel (poloxamer 407). After intravitreal administration in a
      rabbit model, liposomes and liposomes-gel formulations provided, 1-day
      postinjection, significantly higher drug levels than the control solution of the
      oligothymidilate pdT16. In addition, there was no significant difference in the
      amounts of pdT16 found in the vitreous humor between the liposomes and liposomes
      gel. Nevertheless, because of their better stability in the absence of poloxamer,
      liposomes alone allowed to a larger extent to control the delivery of ODNs as
      compared to liposome-gel formulations since 37% of the ODNs were still found in
      the vitreous 15 days after administration. In addition, the ODNs found in the
      vitreous humor were protected against degradation by their encapsulation within
      liposomes. The second approach consisted in designing microspheres allowing to
      release in a controlled fashion pdT16. The ODN was encapsulated within
      poly(lactide-co-glycolide) microspheres alone or associated with polyethylenimine
      (PEI) at different nitrogen/phosphate (N/P) ratios. The introduction of PEI in
      the internal aqueous phase resulted in a strong increase of the ODN encapsulation
      efficiency. PEI affected microsphere morphology inducing the formation of very
      porous particles yielding to an accelerated release of pdT16. Porosity and
      controlled delivery was prevented by introducing sodium chloride in the external
      preparation medium. When incubated with HeLa cells, microspheres encapsulating
      pdT16/PEI complexes allowed an improvement of the intracellular penetration of
      the released ODN. Both liposomes and microspheres are suitable for local delivery
      of ODNs.

PMID- 15158967
TI  - Active and intelligent inhaler device development.
AB  - The dry powder inhaler, which has traditionally relied on the patient's
      inspiratory force to deaggregate and deliver the active agent to the target
      region of the lung, has been a successful delivery device for the provision of
      locally active agents for the treatment of conditions such as asthma and chronic
      obstructive pulmonary disease (COPD). However, such devices can suffer from poor
      delivery characteristics and/or poor reproducibility. More recently, drugs for
      systemic delivery and more high value compounds have been put into DPI devices.
      Regulatory, dosing, manufacturing and economic concerns have demanded that a more
      efficient and reproducible performance is achieved by these devices. Recently
      strategies have been put in place to produce a more efficient DPI
      device/formulation combination. Using one novel device as an example the paper
      will examine which features are important in such a device and some of the
      strategies required to implement these features. All of these technological
      advances are invisible, and may be irrelevant, to the patient. However, their
      inability to use an inhaler device properly has significant implications for
      their therapy. Use of active device mechanisms, which reduce the dependence on
      patient inspiratory flow, and sensible industrial design, which give the patient
      the right clues to use, are important determinants of performance here.

PMID- 15158968
TI  - Tumor targeting based on the effect of enhanced permeability and retention (EPR)
      and the mechanism of receptor-mediated endocytosis (RME).
AB  - This review is focused on the macromolecular drug carrier systems by the effect
      of enhanced permeability and retention (EPR) and the mechanism of receptor
      mediated endocytosis (RME). The effect of EPR is thought to be useful for the
      targeting of the macromolecular drugs to the tumor tissues on a vasculolymphatic
      level. The RME reveals the selective recognition, high affinity binding, and
      immediate internalization for the ligand on a cellular level. In the receptor,
      recognizing transferrin, a level of expression on the tumor cells is higher than
      that on the normal cells. We have used serum albumin and transferrin as drug
      carriers to deliver mitomycin C (MMC) to the tumor tissues and into the tumor
      cells. The properties of the conjugates of MMC to serum albumin and transferrin
      were examined in vitro and in vivo. We concluded that MMC could be delivered to
      the tumor tissue and cells by the use of albumin and transferrin as drug
      carriers.

PMID- 15158969
TI  - Polymeric anticancer drugs with pH-controlled activation.
AB  - The paper is dealing with the synthesis and properties of new, nontargeted or
      antibody-targeted pH-sensitive polymer-doxorubicin (DOX) conjugates designed as
      anticancer drugs facilitating site-specific therapy. These conjugates are stable
      and inactive during transport in the body but activate inside target cells as a
      result of pH changes outside and inside the cells. Cytotoxicity of the conjugates
      depends on the detailed structure of the polymer and of the spacer between the
      drug and polymer carrier. In both protective and therapeutic regimes of drug
      administration, the in vivo antitumor activity of the pH-sensitive conjugates
      containing DOX was significantly enhanced (T-cell lymphoma EL 4, C57BL/16 mice)
      in comparison with the free DOX or classic PK1, the PHPMA-DOX conjugate
      clinically tested at present.

PMID- 15158970
TI  - Cathepsin K inhibitor-polymer conjugates: potential drugs for the treatment of
      osteoporosis and rheumatoid arthritis.
AB  - The role of the newly discovered cysteine protease, cathepsin K, in osteoporosis
      and rheumatoid arthritis is reviewed. The current development of cathepsin K
      inhibitors and their targeted delivery using synthetic polymer carriers are
      discussed. Future challenges and possible strategies to improve these delivery
      systems are addressed.

PMID- 15158971
TI  - Preparation and characterization of water-soluble pH-sensitive nanocarriers for
      drug delivery.
AB  - pH-sensitive drug delivery systems can be engineered to release their contents or
      change their physicochemical properties in response to variations in the acidity
      of the surroundings. The present work describes the preparation and
      characterization of novel polymeric micelles (PM) composed of amphiphilic pH
      responsive poly(N-isopropylacrylamide) (PNIPAM) or poly(alkyl(meth)acrylate)
      derivatives. On one hand, acidification of the PNIPAM copolymers induces a coil
      to-globule transition that can be exploited to destabilize the intracellular
      vesicle membranes. In this work, PNIPAM-based PM were loaded with either
      doxorubicin or aluminium chloride phthalocyanine and their cytotoxicity was
      assessed in murine tumoral models. On the other hand, poly(alkyl(meth)acrylate)
      copolymers can be designed to interact with either hydrophobic drugs or polyions
      and release their cargo upon an increase in pH.

PMID- 15158972
TI  - Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems
      for insulin.
AB  - An oral delivery system for insulin was developed and functional activity was
      tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles
      containing insulin was synthesized in the presence of PEG-3350 and modified by
      aggregating the particles with caseins to obtain the calcium phosphate-PEG
      insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC
      formulation were tested in NOD mice under fasting or fed conditions to evaluate
      the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h
      following the treatments using an ACCU CHECK blood glucose monitoring system.
      Orally administered and subcutaneously injected free insulin solution served as
      controls in the study. Based on the results obtained we propose that: (1). the
      biological activity of insulin is preserved in CAPIC formulation; (2). insulin in
      CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic
      effect after oral administration to diabetic mice; (3). CAPIC formulation
      protects insulin from degradation while passing through the acidic environment of
      the GI track until it is released in the less acidic environment of the
      intestines where it can be absorbed in its biologically active form; (4). CAPIC
      formulation represents a new and unique oral delivery system for insulin and
      other macromolecules.

PMID- 15158973
TI  - Biodegradable dextran hydrogels crosslinked by stereocomplex formation for the
      controlled release of pharmaceutical proteins.
AB  - Hydrogels are based on hydrophilic polymers, which are crosslinked to prevent
      dissolution in water. Because hydrogels can contain large amounts of water, they
      are interesting devices for the delivery of proteins. In this contribution a
      biodegradable dextran hydrogel is described which is based on physical
      interactions and is particularly suitable for the controlled delivery of
      pharmaceutically active proteins. The unique feature of our system is that the
      preparation of the hydrogels takes place in an all-aqueous solution, by which the
      use of organic solvents is avoided. Furthermore, chemical crosslinking agents are
      not needed to create the hydrogels, since crosslinking is established physically
      by stereocomplex formation between enantiomeric oligomeric lactic acid chains.
      The hydrogel is simply obtained after mixing aqueous solutions of dextran(l)
      lactate and dextran(d)-lactate. In this contribution, the formation of the
      hydrogels as well as their protein release properties and degradation behavior
      are discussed.

PMID- 15158974
TI  - Molecularly designed water soluble, intelligent, nanosize polymeric carriers.
AB  - Intelligent polymers, also referred as "stimuli-responsive polymers" undergo
      strong property changes (in shape, surface characteristics, solubility, etc.)
      when only small changes in their environment (changes in temperature, pH, ionic
      strength light, electrical and magnetic field, etc.). They have been used in
      several novel applications, drug delivery systems, tissue engineering scaffolds,
      bioseparation, biomimetic actuators, etc. The most popular member of these type
      of polymers is poly(N-isopropylacrylamide) (poly(NIPA)) which exhibits
      temperature-sensitive character, in which the polymer chains change from water
      soluble coils to water-insoluble globules in aqueous solution as temperature
      increases above the lower critical solution temperature (LCST) of the polymer.
      Copolymerization of NIPA with acrylic acid (AAc) allows the synthesis of both pH
      and temperature-responsive copolymers. This paper summarizes some of our related
      studies in which NIPA and its copolymers were synthesized and used as intelligent
      carriers in diverse applications.

PMID- 15158975
TI  - Polymeric prodrugs.
AB  - In 1975 Prof. H. Ringsdorf proposed a model for rational design of polymeric
      prodrugs [J. Polym. Sci. Symp. 51 (1975) 135]. The model has been the most
      important basis for research in the field, since it was the first model that took
      into account both the chemical and biological aspects needed for the design of
      polymeric prodrugs. This paper deals with the most important properties that were
      discovered by designing polymeric prodrugs: prolongation of action of the drug,
      controlled release of the drug, passive tumor accumulation by the EPR-effect and
      alteration of body distribution and cell uptake. Over the years, other objectives
      have been formulated and other properties of polymer-drug conjugates were
      discovered. One recent example, the immunoprotective ability of polymeric
      prodrugs, is described in more detail in this paper.

PMID- 15158976
TI  - Chemistry of polymer biodegradation and implications on parenteral drug delivery.
AB  - Most polymeric implants are biodegraded by one of two common chemical degradation
      mechanisms: (i). hydrolysis and (ii). oxidation. The chemical structure is among
      the most important factors which affect the biodegradation of polymeric implants.
      Hydrolytic biodegradations are often accompanied by substantial decrease of pH,
      whilst oxidative biodegradation processes are usually very slow due to
      consumption of stoichiometric amounts of oxidising agents. A dramatic
      acceleration of the biodegradation can be expected, if the biodegradation can be
      initiated by catalytic amounts of oxidation agents. Poly(ethylene carbonate)
      (PEC) and poly(trimethylene carbonate) (PTMC) are presumably biodegraded by such
      catalytic oxidation processes. Their biodegradation shows all the characteristics
      of surface erosion. Poly(ethylene carbonate) is utilised as a surface eroding
      biocompatible polymer for controlled delivery of peptide and protein drugs.

PMID- 15158977
TI  - Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms.
AB  - Controlled release gastroretentive dosage forms (CR-GRDF) enable prolonged and
      continuous input of the drug to the upper parts of the gastrointestinal (GI)
      tract and improve the bioavailability of medications that are characterized by a
      narrow absorption window. CR-GRDF provide a means to utilize all the
      pharmacokinetic (PK) and pharmacodynamic (PD) advantages of controlled release
      dosage forms for such drugs. Thus, CR-GRDF may improve therapy with clinically
      used medications, as well as enable oral administration of drugs, or drug
      candidates, that hitherto had to be infused parenterally. This manuscript
      discusses the complexity of the PK and PD factors that influence the treatment
      benefits of CR-GRDF and summarizes the results of our recent in vivo
      investigations in animal models (rats and dogs) and in human subjects. We found
      that a CR-GRDF formulation was superior to the other modes of administration for
      levodopa and riboflavin, but not for metformin. The PK and PD rationales of GRDFs
      for the studied drugs are presented and discussed. We conclude that due to the
      complexity of the PK and PD factors for a certain drug, the rationale for
      continuous administration obtained by CR-GRDF should be assessed and established
      in vivo.

PMID- 15158978
TI  - Combined cancer therapy by micellar-encapsulated drug and ultrasound.
AB  - A new modality of drug targeting to tumors that is under development in our lab
      is based on the drug encapsulation in polymeric micelles followed by a localized
      release at the tumor site triggered by focused ultrasound. The rationale behind
      this approach is that drug encapsulation in micelles decreases systemic
      concentration of drug and provides for a passive drug targeting to tumors via the
      enhanced penetration and retention (EPR) effect, thus, reducing unwanted drug
      interactions with healthy tissues. In addition, polymeric micelles sensitize
      multidrug resistant (MDR) cells to the action of drugs. Upon the accumulation of
      drug-loaded micelles at the tumor site, ultrasonic irradiation of the tumor is
      used to provide for the effective intracellular drug uptake. Ultrasound releases
      drug from micelles and enhances the intracellular uptake of both released and
      encapsulated drug. An important advantage of ultrasound is that it is
      noninvasive, can penetrate deep into the interior of the body, can be focused and
      carefully controlled. The results of the in vitro application of this technique
      for delivering anthracyclin drugs to ovarian carcinoma A2780 drug-sensitive and
      MDR cells are described.

PMID- 15158979
TI  - The healing effect of TGF-alpha on gastric ulcer induced by acetylsalicylic acid
      in rats.
AB  - The present study was designed to investigate the effects of microemulsion and
      aqueous solution containing transforming growth factor alpha (TGF-alpha) and/or
      aprotinin administered intragastrically (i.g.) on healing of acute gastric ulcers
      induced by acetylsalicylic acid (ASA). The microemulsion was prepared by
      modification of the microemulsion formulation described in our previous study.
      Acute gastric lesions were induced by the application of ASA (150 mg/kg in 1.5 ml
      of 0.2N HCl i.g.). TGF-alpha in solution or microemulsion formulations were
      administered at a dose of 10 microg/kg per 24h i.g. for 2 days. The effects of
      TGF-alpha on the healing was evaluated with the measurement of ulcer score, basal
      gastric acid secretion, total protein content of gastric fluid, gastric mucus
      level and histological analysis. The results indicated that the highest decrease
      in ulcer area was observed in group treated with microemulsion containing TGF
      alpha plus aprotinin (TA-ME). TGF-alpha in microemulsion formulation was more
      effective than TGF-alpha in solution formulation in the increase of gastric mucus
      secretion, in the decrease of gastric acid secretions and ulcer scores.
      Histological evaluation of the gastric mucosa samples revealed that, best
      recovery was obtained in the TA-ME treated group.

PMID- 15158980
TI  - Development of a buccal bioadhesive nicotine tablet formulation for smoking
      cessation.
AB  - Bioadhesive buccal tablet formulations for delivery of nicotine into the oral
      cavity were developed. Carbomer (Carbopol)974P NF) (CP) and alginic acid sodium
      salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl
      methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated
      into the formulations as a pH increasing agent. In vitro release and bioadhesion
      studies were performed on the developed tablets. In the formulations containing
      CP:HPMC, the NHT released increased with the increasing HPMC concentration
      whereas a decrease was observed with increasing HPMC concentration in
      formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets
      containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05)
      but increased significantly with the increasing CP concentration (P>0.05). A
      decrease in pH of the dissolution medium to acidic values was avoided by
      incorporation of magnesium hydroxide into the formulations. The developed
      formulations released NHT for 8h period, and remained intact except for the
      formulation containing CP:HPMC at 20:80 ratio.

PMID- 15158981
TI  - Phytochemical and antiinflammatory studies on Terminalia catappa.
AB  - The antiinflammatory activity of Terminalia catappa leaves ethanolic extract was
      studied using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in
      acute and chronic models. A bioassay-oriented fractionation procedure showed that
      the activity concentrates in the chloroform fraction. Ursolic acid (1) and
      2alpha,3beta,23-trihydroxyurs-12-en-28-oic acid (2), isolated from the chloroform
      fraction, exhibited strong antiinflammatory activities. The results suggest that
      the triterpenic acids 1 and 2 are responsible for the antiinflammatory activity
      of T. catappa leaves.

PMID- 15158982
TI  - Scopoletin suppresses pro-inflammatory cytokines and PGE2 from LPS-stimulated
      cell line, RAW 264.7 cells.
AB  - Scopoletin (1-50 microg/ml) inhibited the release of PGE2, TNF-alpha, IL-1beta
      and IL-6 and suppressed the expression of COX-2 in a concentration-dependent
      manner. These results suggest that scopoletin might suppress the production of
      such pro-inflammatory cytokines and exert inhibitory activity on LPS-induced PGE2
      production through the depression of COX-2 expression.

PMID- 15158983
TI  - Determination of hesperetin, cinnamic acid and nicotinic acid in propolis with
      micellar electrokinetic capillary chromatography.
AB  - Micellar electrokinetic capillary chromatography (MEKC) has been used to
      determine hesperetin, cinnamic acid and nicotinic acid in propolis. After
      systematically study the effect of buffer concentration and pH, micellar
      concentration, organic modifier, applied voltage and injection time, the
      analytical conditions were optimized. Under the optimized conditions, the three
      analytes could be well separated in 20 min. A good linearity between the peak
      current and the concentration was found in the range of 0.02-0.60 mg/ml, 0.05
      1.20 mg/ml and 0.10-1.40 mg/ml with correlation coefficients of 0.9989, 0.9995
      and 0.9990 for hesperetin, cinnamic acid and nicotinic acid, respectively. The
      detection limits were 0.006 mg/ml (hesperetin), 0.017 mg/ml (cinnamic acid) and
      0.036 mg/ml (nicotinic acid). The validity of the method was verified by
      analyzing the three analytes in propolis oral liquids.

PMID- 15158984
TI  - Ethnopharmacology of ogliastra (villagrande strisaili, sardinia, Italy).
AB  - The use of medicinal and aromatic plants was investigated in a group of 200
      elderly people (60-104-year-old) from Villagrande Strisaili (Ogliastra, Sardinia,
      Italy), recording the use of 78 species for the treatment of various ailments,
      especially of the respiratory tract, the mouth, and the skin. Seventeen plants
      had never been described as medicinal species in peninsular Italy, while a few
      others turn out to have an original use for Sardinia.

PMID- 15158985
TI  - Production of two volatile glucosinolate hydrolysis compounds in Nasturtium
      montanum and Cleome chelidonii plant cell cultures.
AB  - Callus and suspension cultures established from Nasturtium montanum and Cleome
      chelidonii were shown to produce glucosinolates by analysis of their hydrolysis
      products. Large increases in two glucosinolate hydrolysis products were noted
      when cultures were supplemented with L-cysteine and L-methionine, and further
      increases were produced in N. montanum with l-tryptophan supplementation.

PMID- 15158986
TI  - Immunomodulatory activities of fractions from hot aqueous extract of wood from
      Clausena excavata.
AB  - The effects of fractions from hot aqueous extract, acetone extract and the
      folklore preparation of Clausena excavata were studied on mouse splenocyte
      proliferation. The fractions of hot aqueous and acetone extracts were found to be
      the most active. On the contrary, the fractions from the crude folklore
      preparation resulted less active. This result could partly explain the popularity
      of this plant in folk medicine as a remedy for cancer and HIV patients in the
      eastern part of Thailand.

PMID- 15158987
TI  - Anticonvulsant activity of Mimosa pudica decoction.
AB  - The decoction of Mimosa pudica leaves given intraperitoneally at dose of 1000
      4000 mg/kg protected mice against pentylentetrazol and strychnine-induced
      seizures. M. pudica had no effect against picrotoxin-induced seizures It also
      antagonized N-methyl-D-aspartate- induced turning behavior. These properties
      could explain its use in African traditional medicine.

PMID- 15158988
TI  - Rosmarinic acid from Zataria multiflora tops and in vitro cultures.
AB  - Rosmarinic acid (RA) was obtained from Zataria multiflora tops' extract and its
      structure was confirmed by spectroscopic methods. Various in vitro cultures were
      established on Murashige and Skoog (MS) or Modified Tobacco (MT) medium
      containing growth hormones. The results indicated that cultures of Z. multiflora
      biosynthesize RA (55-355 mg/100 g dry wt.) and the highest accumulation were
      reached on MT media containing NAA 2 mg/l.

PMID- 15158989
TI  - Haematological evaluation of ethanolic extract of Allium ascalonicum in male
      albino rats.
AB  - The haematological effect of ethanolic extract of Allium ascalonicum was
      evaluated in male albino rats during a 21 day administration at the doses of 50,
      100 and 200 mg/kg b.w, orally. Parameters evaluated include the serum lipids, red
      and white cell indices. The results showed that the extract administered
      decreased most of the parameters relating to red cell and increased most of those
      parameters relating to white cells. It also decreased the total cholesterol
      (TCH), high density lipoprotein cholesterol (HDL) and low density lipoprotein
      cholesterol (LDL) with no significant effect on the triglyceride levels.

PMID- 15158990
TI  - Oleanene constituents of Lantana cujabensis.
AB  - A new compound, 3beta,25-epoxy-3alpha-hydroxy-22beta-isobutanoyloxyolean-12-ene
      28-oic acid (1), and two known triterpenoids lantanilic acid (2) and camaric acid
      (3) were isolated from the stem and leaves of Lantana cujabensis. Their
      structures were elucidated by spectroscopic methods. The ethanol extracts did not
      show significant in vitro antiplasmodial activity against chloroquine-sensitive
      or resistant strains of Plasmodium falciparum.

PMID- 15158991
TI  - Morinda lucida extract induces endothelium-dependent and -independent relaxation
      of rat aorta.
AB  - The effect of an aqueous extract of Morinda lucida (ML) on vascular tone was
      tested using rat aortic rings precontracted with noradrenaline (10(-7) mol/l).
      Relaxation responses were determined with endothelium-intact, L-NAME-treated,
      methylene blue-treated and endothelium-denuded tissues. In the concentration
      range of 0.25-9.0 mg/ml, ML elicited vasorelaxation in noradrenaline
      precontracted rings. This relaxation response was partially attenuated by removal
      of the endothelium, and completely inhibited by pretreatment of rings with L-NAME
      and methylene blue. Thus, ML-induced relaxation of vascular smooth muscle occurs
      via endothelium-dependent and -independent mechanisms, the former of which
      involves the nitric oxide-cGMP pathway.

PMID- 15158992
TI  - Hematopoietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its
      application to a biological response modifier.
AB  - Ginsenoside Rg3, which is obtained as a by-product during the steaming of red
      ginseng, at 300 microg/ml enhanced the proliferation of the total spleen and bone
      marrow (BM) cells in both the cyclophosphamide (CYC)-treated and non-CYC-treated
      groups.

PMID- 15158993
TI  - HPLC-DAD-MS identification of bioactive secondary metabolites from Ferula
      communis roots.
AB  - A simple HPLC method was developed to distinguish between 'poisonous' and 'non
      poisonous' chemotypes of Ferula communis. The method was performed on a C8
      reverse phase analytical column using a binary eluent (aqueous TFA 0.01%-TFA
      0.01% in acetonitrile) under gradient condition. The two chemotypes showed
      different fingerprints. The identification of five coumarins and eleven daucane
      derivatives by HPLC-diode array detection (HPLC-DAD) and HPLC-MS is described. A
      coumarin, not yet described, was detected.

PMID- 15158994
TI  - Cytotoxicity and antibacterial activity of extractives from Wedelia calendulacea.
AB  - The cytotoxicity and antibacterial activity of petroleum ether, chloroform and
      methanol extracts of Wedelia calendulacea were assayed by brine shrimp lethality
      bioassay and standardized disk diffusion method against 19 bacterial strains.
      Three diterpenes isolated from the plant were also evaluated for in vitro
      antibacterial activities. The LC50 for the crude extracts against the brine
      shrimp nauplii were found to be 4.59 microg/ml, 7.99 microg/ml and 14.88
      microg/ml, respectively, whereas the positive control, vincristine sulfate showed
      an LC50 of 0.58 microg/ml. Among the crude extracts and pure compounds tested, (
      )-kaur-16-en-19-oic acid isolated from the chloroform extract showed the highest
      inhibitory activity against most of the bacterial strains with mean zone of
      inhibition of 10-21 mm at 200 microg/disc.

PMID- 15158995
TI  - Antibacterial and brine shrimp lethality tests of biflavonoids and derivatives of
      Rheedia gardneriana.
AB  - The hydroalcoholic extract of the leaves from Rheedia gardneriana yielded
      volkensiflavone (1), fukugetin (2), fukugiside (3), GB2a-I-7-O-glucoside (4) and
      epicatechin (5). Compounds 1-5, and some derivatives of 1 and 2 were evaluated
      for lethality to brine shrimp larvae and for antibacterial activity.

PMID- 15158996
TI  - Effect of Helicteres isora root extracts on glucose tolerance in glucose-induced
      hyperglycemic rats.
AB  - The ethanol, ethyl acetate and butanol extracts of Helicteres isora root showed
      significant oral hypoglycemic activity on glucose loaded rats at a dose of 250
      mg/kg. The butanol extract showed maximum antihyperglycemic activity and effect
      being comparable to that of glibenclamide.

PMID- 15158997
TI  - Antimicrobial and cytotoxic activities of the fruit essential oil of Xylopia
      aethiopica from Nigeria.
AB  - The fruits essential oil of Xylopia aethiopica showed activity against four
      microorganisms and cytotoxicity to carcinoma cells (Hep-2 cell line) at 5 mg/ml
      concentration.

PMID- 15158998
TI  - Variability in the content of active constituents and biological activity of
      Glycyrrhiza glabra.
AB  - Nine samples of Glycyrrhiza glabra were collected in various sites of Calabria,
      Italy, with the aim to determine the variability in the confront of active
      constituents and in antibacterial and antifungal activities of the extracts. The
      samples showed remarkable differences in chemical composition and biological
      activity.

PMID- 15158999
TI  - Antiproliferative activity of Thai medicinal plant extracts on human breast
      adenocarcinoma cell line.
AB  - Ethanolic extracts of selected nine Thai medicinal plants were tested for
      antiproliferative activity against SKBR3 human breast adenocarcinoma cell line
      using MTT assay. Garcinia mangostana showed the most potent activity. However,
      all plant extracts showed activity in potential range for further investigation
      on cancer cells.

PMID- 15159000
TI  - Hyaluronidase and protease activities from Indian snake venoms: neutralization by
      Mimosa pudica root extract.
AB  - The aqueous root extract of Mimosa pudica dose dependently inhibited the
      hyaluronidase and protease activities of Indian snakes (Naja naja, Vipera
      russelii and Echis carinatus) venom.

PMID- 15159001
TI  - Trypanocidal properties of Mikania stipulacea and Mikania hoehnei isolated
      terpenoids.
AB  - The in vitro trypanocidal properties of isolated terpenoids from Mikania
      stipulacea and Mikania hoehnei were investigated in Trypanosoma cruzi Y strain.
      Both compounds, the diterpene ent-9alpha-hydroxy-15beta-E-cinnamoyloxy-16-kauren
      19-oic acid (1) and the sesquiterpene lactone 8beta-hydroxyzaluzanin D (2) were
      active.

PMID- 15159002
TI  - The in vitro antibacterial/synergistic activities of Withania somnifera extracts.
AB  - The methanol, hexane and diethyl ether extracts from both leaves and roots of
      Withania somnifera were evaluated for the antibacterial/synergistic activity by
      agar plate disc-diffusion assay against Salmonella typhimurium and Escherichia
      coli. Different concentrations of Tibrim, a combination of rifampicin and
      isoniazid, were tested to find out the minimum inhibitory concentration (MIC),
      which came out to be 0.1 mg/ml for S. typhimurium and E. coli. From the six
      extracts tested, only methanol and hexane extracts of both leaves and roots were
      found to have potent antibacterial activity. A synergistic increase in the
      antibacterial effect of Tibrim was noticed when MIC of Tibrim was supplemented
      with these extracts.

PMID- 15159003
TI  - Antifungal potential of Indian medicinal plants.
AB  - Fourteen Indian plants, selected based on their use in respiratory and other
      disorders in traditional systems of medicine, were analyzed for their potential
      activity against fungi. The antifungal activity was investigated by disc
      diffusion, microbroth dilution and percent spore germination inhibition tests
      against pathogenic Aspergilli. Methanolic extracts of Solanum xanthocarpum and
      Datura metel inhibited the growth of Aspergillus fumigatus, A. flavus and A.
      niger and their in vitro MICs were found to be 1.25-2.50 mg/ml by both microbroth
      dilution and percent spore germination assays. In disc diffusion assay, a
      concentration of 0.062 mg/disc of methanol extract of D. metel showed significant
      activity against Aspergilli. S. xanthocarpum exhibited similar activity at 0.125
      mg/disc.

PMID- 15159004
TI  - Biological activity of phenolic compounds from Alchornea glandulosa.
AB  - From the isopropyl acetate fraction obtained by partition of the leaves ethanolic
      extract of Alchornea glandulosa, six phenolic compounds were isolated and
      identified. General lethality of the extract, fractions and compounds were
      assayed with Brine Shrimp Test (BST) and with Antifeedant Activity Bioassay (AAB)
      against neonate larvae of Spodoptera frugiperda. Aqueous fraction and ethyl
      gallate, one of the major constituents of the polar fraction, have shown the
      highest toxicity in BST. Ethanolic extract, isopropyl acetate fraction and gallic
      acid reduced significantly larval growth of S. frugiperda neonates.

PMID- 15159005
TI  - Antimicrobial activity of the macrofungus Pholiota adiposa.
AB  - The 60% methanolic extract of Pholiota adiposa exhibited antimicrobial activity.

PMID- 15159006
TI  - In vitro antioxidant activity of species collected in Parana.
AB  - Hydroalcoholic extracts of 10 medicinally used species collected from the area
      covered by a reservoir due to a dam built for the Salto Caxias Hydro-electric
      power plant in the State of Parana, Southern Brazil, and Casearia sylvestris,
      were investigated for their potential antioxidant activity against DPPH (1,1
      diphenyl-2-picrylhydrazyl) free radicals and by the phosphomolybdenum method. The
      extract of Bauhinia microstachya was found to be the most potent in both models.

PMID- 15159007
TI  - Antifungal activity of fruit pulp extract from Psidium sartorianum.
AB  - The methanol extract of the fruit pulp of Psidium sartorianum was evaluated
      against seven Candida spp. and nine other fungal strains that are human
      pathogens. The extract showed a significant activity against seven Trichophyton
      species. Candida species were insensitive.

PMID- 15159008
TI  - Biological screening of Bangladeshi mango mistletoe bark extracts.
AB  - The ethyl acetate extract of the Bangladeshi mango mistletoe (Loranthus globosus)
      bark was found to be most effective against both Gram (+) and Gram (-) bacteria
      and it also showed good cytotoxicity with a LC50 10.83 microg/ml.

PMID- 15159009
TI  - Antimicrobial activity of Memecylon malabaricum leaves.
AB  - The petroleum ether, chloroform and methanol extracts of Memecylon malabaricum
      leaves were tested for antimicrobial activity. Only methanol extract has shown
      activity against bacteria both Gram (+) and Gram (-), and fungi.

PMID- 15159010
TI  - Antibacterial and antifungal activities of Euroschinus papuanus.
AB  - The crude methanolic extracts of the leaves, stem bark, stem heart wood, root
      bark and root heart wood of Euroschinus papuanus and the fractions obtained on
      partitioning with petrol, dichloromethane (D), ethyl acetate (E) and butanol (B),
      exhibited a broad spectrum antibacterial activity. Fractionation drastically
      enhanced the activity. Excellent activity was demonstrated by the E fractions of
      stem heart wood, D of root bark, and E of root heart wood. Antifungal activity
      was exhibited by the B fractions of leaves, stem heartwood and root bark.

PMID- 15159011
TI  - A new phenolic glycoside from Sorocea ilicifolia stem bark.
AB  - A new phenolic glycoside, 3,4-dimethoxyphenyl-1-O-beta-d-apiofuranosyl (1-->2)
      beta-d-glucopyranoside (1), was isolated from the acetone extract of the Sorocea
      ilicifolia stem bark, along with the known compounds, 3,4,5-trimethoxyphenyl-1-O
      beta-apiofuranosyl (1-->6)-beta-d-glucopyranoside, benzyl-O-beta-d-apiofuranosyl
      (1-->2)-beta-d-glucopyranoside, sorocein A, mulberrofuran K, kuwanon J, sorocein
      B, chalcomoracin, and kuwanol E.

PMID- 15159012
TI  - A new nitroethylphenolic glycoside from Semiaquilegia adoxoides.
AB  - The isolation of a new nitroethylphenolic glycoside, 4-hydroxy-1-(2-nitroethyl)
      benzene 4-O-(6'-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside (1), from the
      roots of Semiaquilegia adoxoides is reported.

PMID- 15159013
TI  - Chemical constituents from Tillandsia recurvata.
AB  - The CHCl3 extract of Tillandsia recurvata yielded 5,3'-dihydroxy-6,7,8,4'
      tetramethoxyflavanone (1), 1,3-di-O-cinnamoyl-glycerol (2) and ethyl ester of
      caffeic acid. Their structures were elucidated by means of spectroscopic methods
      such as mass spectroscopy and 1 and 2D-NMR.

PMID- 15159015
TI  - Insulin can modulate MCF-7 cell response to paclitaxel.
AB  - Insulin regulates metabolism through homologous receptor tyrosine kinases, and
      plays a role in proliferation of breast cancer cells. Our research studied
      whether insulin, administered separately or in combination with paclitaxel,
      interferes with paclitaxel-mediated biological activity in human breast cancer
      cells. Not only did insulin influence paclitaxel-mediated cell microtubule
      reorganization, but it also influenced MCF-7 cell sensitivity to paclitaxel.
      Furthermore, combined administrations of insulin and paclitaxel affected MAPK
      pathway, Raf-1 activation and p53 expression levels. Our findings indicate that
      insulin seems to modulate MCF-7 cell response to paclitaxel; consequently,
      elevated levels of insulin could influence tumor cell resistance.

PMID- 15159014
TI  - GST profiling may be useful in the screening for thyroid nodule malignancy.
AB  - Screening tools are of utmost necessity in order to identify individuals at risk
      for thyroid nodule cancer. The polymorphic inheritance of human drug-metabolizing
      enzymes, such as those encoded by the Glutathione-S-Transferase (GST) system,
      plays an important role in the development of most human cancers. GSTP1 enzyme is
      the most important detoxification enzyme in human head and neck tissues. An
      aminoacid substitution (1105V) in the GSTP1 gene result in two genotypes, GSTP1AB
      and GSTP1BB. Those produce a variant enzyme with lower activity and less
      capability of effective detoxification of carcinogens than the wild type GSTP1AA.
      In order to look for the influence of GSTP1 enzymes inheritance pattern on
      thyroid cancer risk we used a PCR-SSCP-sequencing approach to compare the
      genotypes of 98 malignant nodules, including 77 papillary carcinomas (PC) and 21
      follicular carcinomas (FC), to 44 benign nodules and to 157 healthy control
      individuals. Individuals with history of previous thyroid disease, exposure to
      radiation and antecedents of malignancy were excluded. Patients with PC and FC
      showed a significant over-representation of the variants of GSTP1 allele compared
      to the control population (p < 0.0001 The risk for thyroid cancer in individuals
      with the variant GSTP1 enzymes, after adjusting for gender, age, tobacco and
      drugs use, increased 7,092 (CI: 2,307-21,802) and 9,625 (CI: 2.484-37.291) times
      for PC and FC, respectively. We suggest that GST genotype may be associated with
      an increased susceptibility to thyroid cancer. GSTP1 profiling from peripheral
      blood may be a simple and useful tool in the screening for thyroid nodule
      malignancy. Glutathione-S-Transferase system; GSTP; Thyroid cancer; Screening.

PMID- 15159017
TI  - Regulatory mechanism of glutathione S-transferase P-form during chemical
      hepatocarcinogenesis: old wine in a new bottle.
AB  - The expression of glutathione S-transferase P-form (GST-P) is markedly up
      regulated in the initial phase of chemical hepatocarcinogenesis. It is unlikely
      that a specific genetic change is associated with this common response to a
      variety of carcinogens. Here, we describe how GST-P gene expression is induced by
      carcinogenic treatment, focusing on the changes in the network of liver-enriched
      transcription factors, including CCAAT/enhancer-binding proteins. Although the
      balance of positive and negative transcription factors regulates the expression
      of the GST-P gene, additional factors such as the altered regulation of growth
      control may certainly be necessary for these cells to develop into preneoplastic
      foci. Furthermore, our genetic analyses on the tumor susceptibility of (F344 x
      DRH)F2 rats support the hypothesis that the formation of GST-P-positive lesions
      is required but is not directly associated with final malignant transformation.

PMID- 15159016
TI  - Black tea protects immunocytes from tumor-induced apoptosis by changing Bcl-2/Bax
      ratio.
AB  - It is known that cancer is associated with altered immune function. We
      demonstrated earlier that black tea inhibits tumor growth in a dose-dependent
      manner. Here, we report that apoptosis was the cause of immunocyte death in
      Ehrlich's ascites carcinoma (EAC)-bearing mice and anti-tumor dose of black tea
      restored EAC-induced immunosuppression by inhibiting apoptosis. A search for the
      molecular mechanism revealed that EAC burden increased the expression of the pro
      apoptotic proteins p53 and Bax in splenic lymphocytes although did not change the
      level of pro-proliferative protein Bcl-2. Interestingly, anti-tumor dose of black
      tea down-regulated p53, decreased Bax while augmenting Bcl-2 in these cells. As a
      result, Bcl-2/Bax ratio was increased and the immunocytes were protected from
      tumor-induced apoptosis. Thus, unlike many other anti-cancer agents, black tea is
      not only devoid of immunosuppressive effect but also acts as immuno-restorer in
      tumor-bearing host. These results, thus, raise the possibility of inclusion of
      black tea in successful therapeutic regimen against cancer.

PMID- 15159018
TI  - The anti-ischemia agent ranolazine promotes the development of intestinal tumors
      in APC(Min/+) mice.
AB  - Ranolazine was shown to improve exercise parameters in patients with chronic
      angina. It works by switching myocardial energy metabolism from fatty acids to
      glucose, thus increasing the efficiency of ATP production under hypoxic
      conditions. Tumors are hypoxic and may also respond to ranolazine. We found that
      ranolazine caused a dose-dependent increase in tumor number in APC(Min/+) mice, a
      model of spontaneous intestinal tumorigenesis. Tumors from drug-treated mice were
      also more dysplastic and invasive than those from untreated mice. These findings
      have implications for the use of ranolazine in patients with a history of
      malignant neoplasms or adenomatous polyps.

PMID- 15159019
TI  - Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles.
AB  - The following study examines the feasibility of nanoshell-assisted photo-thermal
      therapy (NAPT). This technique takes advantage of the strong near infrared (NIR)
      absorption of nanoshells, a new class of gold nanoparticles with tunable optical
      absorptivities that can undergo passive extravasation from the abnormal tumor
      vasculature due to their nanoscale size. Tumors were grown in immune-competent
      mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT).
      Polyethylene glycol (PEG) coated nanoshells (approximately 130 nm diameter) with
      peak optical absorption in the NIR were intravenously injected and allowed to
      circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4
      W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy
      and tumor free >90 days later. Control animals and additional sham-treatment
      animals (laser treatment without nanoshell injection) were euthanized when tumors
      grew to a predetermined size, which occurred 6-19 days post-treatment. This
      simple, non-invasive procedure shows great promise as a technique for selective
      photo-thermal tumor ablation.

PMID- 15159020
TI  - Down-regulation of protein kinase Ceta by antisense oligonucleotides sensitises
      A549 lung cancer cells to vincristine and paclitaxel.
AB  - Previous studies point to protein kinase C (PKC) isozyme eta as a resistance
      factor in cancer cells. Therefore, we investigated whether down-regulation of
      PKCeta with second generation antisense oligonucleotides (ODNs) would sensitise
      A549 human lung carcinoma cells to cytostatics. The effects were compared to the
      outcome of Bcl-xL down-regulation. Upon treatment with antisense ODNs, PKCeta and
      Bcl-xL were both significantly reduced on mRNA and protein level. Down-regulation
      of either PKCeta or Bcl-xL in combination with vincristine or paclitaxel resulted
      in a significant increase in caspase-3 activity compared to that in the control
      oligonucleotide treated cells. In addition, PKCeta down-regulation augmented
      vincristine-induced dissipation of mitochondrial transmembrane potential. In
      conclusion, these results confirm that PKCeta might represent a considerable
      resistance factor and an interesting target to improve anticancer chemotherapy.

PMID- 15159021
TI  - Gene expression profiling reveals novel targets of estramustine phosphate in
      prostate cancer cells.
AB  - Estramustine phosphate (EMP) is a compound widely used for the treatment of
      hormone-refractory prostate cancer. In order to better understand the precise
      molecular mechanism(s) by which EMP exerts its effects on hormone-resistant PC3
      prostate cancer cells, we have utilized microarray to interrogate 22,215 known
      genes to determine the gene expression profiles altered by EMP treatment. The
      purpose of this investigation was to identify gene expression profile first and
      then in future studies determine the specific role of these genes in EMP-induced
      apoptosis in prostate cancer cells. We found a total of 726 genes which showed >2
      fold change after EMP treatment. Clustering analysis showed 12 different types of
      expression alteration. These genes were also subjected to cluster analysis
      according to their biological functions. We found that EMP regulated the
      expression of genes, which are critically involved in the regulation of cell
      growth, cell cycle, apoptosis, iron homeostasis, cytoskeleton and cell signaling
      transduction. Real-time quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) analysis was used to confirm the results of microarray, and the
      results of real-time quantitative RT-PCR were consistent with the microarray
      data. From these results, we conclude that EMP caused changes in the expression
      of a large number of genes that are related to the control of cell survival and
      physiological behaviors. The gene expression profiles may provide comprehensive
      molecular mechanism(s) by which EMP exerts its pleiotropic effects on prostate
      cancer cells. EMP-induced regulation of these genes may be further exploited for
      devising therapeutic strategies for prostate cancer.

PMID- 15159023
TI  - DLC1 is unlikely to be a primary target for deletions on chromosome arm 8p22 in
      head and neck squamous cell carcinoma.
AB  - Allelic imbalance on chromosome arm 8p is common in head and neck squamous cell
      carcinoma (HNSCC). DLC1, a tumour suppressor gene inactivated in liver
      carcinogenesis and encoding a Rho GTPase activating protein (RhoGAP) maps to one
      of the deleted regions (8p21.3-22). In order to determine whether inactivation of
      DLC1 is involved in HNSCC, we have screened tumour cell lines for DLC1 mutations
      and expression. Pathological mutations were not identified in any of the 17 cell
      lines tested. Seven polymorphisms were identified; 13 of the 17 of cell lines
      were homozygous for all seven polymorphisms compared to only 2 of 17 controls
      suggesting a loss of heterozygosity in a majority of the cell lines. DLC1
      expression was observed in all 11 HNSCC cell lines tested, thus excluding the
      possibility of transcriptional silencing of DLC1 by promoter hypermethylation.
      Overall, our data suggest that hemizygous deletions of the DLC1 locus are
      frequent in HNSCCs but this gene is unlikely to be primary target for
      inactivation on this chromosomal arm.

PMID- 15159022
TI  - Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma
      cells.
AB  - Several studies have documented the important association between hepatitis C
      virus (HCV) infection and hepatocellular carcinoma. The mechanisms involved are
      still unknown and could involve viral proteins. We investigated the effect of HCV
      core protein on DNA repair after UV-induced DNA damage. Therefore, we developed
      and characterized stably transfected HepG2 cell lines that express HCV-core
      protein as demonstrated by immunohistochemistry. These cells were significantly
      less capable to repair the DNA damage than control cells. This suppression of DNA
      repair by HCV-core protein renders the cells more sensitive to acquire mutations
      that in combination with enhanced in vivo cell turnover in the infected liver
      might increase the likelihood of malignant transformation of HCV-infected cells
      by other viral factors or upon exposure to environmental factors (food, drugs,
      smoking, alcohol, etc.). Interestingly, expression of the full-length HCV core
      did increase the cell doubling time in one of the cell lines we had developed
      that could not be attributed to an increase in apoptosis or change in telomerase
      activity in these cells.

PMID- 15159024
TI  - Molecular and functional characteristics of erbB2 in normal and cancer breast
      cells.
AB  - The expression pattern of erbB2 and its transmembrane polymorphisms (Ile654Val
      and Ile655Val) were investigated in a panel of human normal and neoplastic breast
      cell lines to evaluate whether the expression pattern was affected by changes in
      the gene structure. At least two peptides of lower molecular mass forms (95 and
      68 kDa) than the holoreceptor (185 kDa), comprehensive of the tyrosine kinase
      domain, were detected in all cells. Both peptides were also phosphorylated,
      suggesting a functional role in signal transduction. The presence of the
      polymorphisms found in two cell lines was unrelated to the expression of the
      lower molecular mass proteins.

PMID- 15159025
TI  - RA-VII, a cyclic depsipeptide, changes the conformational structure of actin to
      cause G2 arrest by the inhibition of cytokinesis.
AB  - In L1210 cells, RA-VII (0.1-100 nM) caused the concentration-dependent inhibition
      of the proliferation and G2 arrest. Treatment of PC12 cells with 10 nM RA-VII
      changed cell shape round with binucleation, suggesting the inhibition of
      cytokinesis. The fluorescence intensity of FITC-phalloidin bound to F-actin was
      enhanced by RA-VII. In surface plasmon resonance experiments, the signal of F
      actin was modified by RA-VII in close agreement with a concentration of FITC
      phalloidin binding to F-actin. These results suggest that RA-VII causes the
      conformational change of F-actin and the stabilization of actin filaments to
      induce G2 arrest.

PMID- 15159026
TI  - A DNA methylation pattern similar to normal tissue is associated with better
      prognosis in human cervical cancer.
AB  - Promoter hypermethylation has been recognized to play an important role in
      carcinogenesis. We analyzed the methylation status of 25 genes in 14 normal
      cervical tissue specimens and in 65 tissue specimens from cervical cancer
      patients using the MethyLight technique. Most of the analyzed genes have been
      shown to be methylated in various cancers. RB1 was never methylated in any
      analyzed cervical tissue. DNA methylation status of the remaining 24 genes in
      every tissue sample was subsequently analyzed using unsupervised agglomerative
      hierarchical cluster analysis to group specimens and CpG regions. We observed
      four clusters. All normal cervical tissue specimens were grouped together in one
      cluster. Neither grade, nor histological type nor age demonstrated any
      significant association with clusters formed. Interestingly, statistically
      significantly less patients whose tumor DNA methylation pattern clustered
      together with normal cervical tissue died within our observation period, as
      compared to those patients out of the three remaining clusters (P < 0.03)
      Cervical cancer patients, whose DNA methylation pattern clustered together with
      normal cervical tissue revealed a strong trend to better survival (P = 0.066)
      compared to patients grouped in the remaining cluster. This study shows for the
      first time that working solely with DNA methylation pattern a subgroup of
      cervical cancer patients can be defined that demonstrated strong similarity to
      non-neoplastic probands and had a better prognosis.

PMID- 15159027
TI  - Overexpressed progesterone receptor form B inhibit invasive activity suppressing
      matrix metalloproteinases in endometrial carcinoma cells.
AB  - In this study, we focused on the influence of progesterone and its receptor in
      invasion and MMPs on endometrial carcinoma cells. The growth of Ishikawa cells,
      to which an progesterone receptor form B (PR-B) expressing vector was
      transfected, was inhibited by progesterone as was the inhibition of the
      expression of cyclin D1. By invasion assay, in conditions with progesterone, the
      invasiveness of Ishikawa cells was inhibited as well as the expression of
      (metalloproteinase) MMP-1, -2, -7 and -9 and Ets-1 decreased. These results
      suggest that activation of PR-B by progesterone results in tumor suppression by
      inhibiting cell growth and invasiveness via suppression of the expression of
      MMPs.

PMID- 15159028
TI  - Expression of the RNA-binding protein CRD-BP in brain and non-small cell lung
      tumors.
AB  - The coding region determinant-binding protein (CRD-BP) is an RNA binding protein
      that recognizes c-myc and IGF-II leader 3 mRNAs as well as the oncofetal H19 RNA.
      CRD-BP exhibits an oncofetal pattern of expression and has been detected in the
      majority of colon (81%), breast (58.5%) and sarcoma (73%) tumors. The study of
      CRD-BP expression was extended in brain tumors and Non small cell lung (NSCL)
      carcinomas and 12/24 malignant, 2/5 benign neuroepithelial tumors and 4/15 of
      NSCL carcinomas were found positive. All normal matching tissues tested were
      found negative. The highest frequency (60%) of CRD-BP positive tumors was
      observed in meningiomas, either benign (11/18) or atypical (3/3). These findings
      confirm that CRD-BP expression is restricted in tumors; the frequency of its de
      novo expression may vary according to tumor type and appears to be an early event
      in the transformation process.

PMID- 15159029
TI  - Regulation of cytokine production in carcinoembryonic antigen stimulated Kupffer
      cells by beta-2 adrenergic receptors: implications for hepatic metastasis.
AB  - Elevated Carcinoembryonic antigen (CEA) levels in the serum indicate a poor
      prognosis for colorectal cancer patients. Induction of proinflammatory cytokines
      by CEA interaction with Kupffer cells has been proposed as a mechanism for
      hepatic metastasis formation. Studies show that the cytokine response in
      circulating and peritoneal macrophages is regulated by beta-adrenergic receptor
      signals, though little information is available regarding Kupffer cells. We
      investigated the relationship between beta-adrenergic receptor stimulation and
      the response of Kupffer cells to CEA. Comparisons between unstimulated and CEA
      stimulated rat Kupffer cells, using cDNA arrays, showed up-regulation (>4 fold)
      of the beta2-adrenergic receptor mRNA. Peak up-regulation occurred after 30 min
      with a decline at 1 h. We examined the effects of the specific beta2-adrenergic
      receptor agonist terbutaline on cytokine production by CEA stimulated rat Kupffer
      cells. Pre-treatment of Kupffer cells with terbutaline followed by CEA caused a
      significant increase in IL-6 and IL-10 production, but a significant reduction in
      TNF-alpha production (>3 fold). mRNA levels reflected those of the ELISA assays
      for IL-6 and IL-10 but not for TNF-alpha. For IL-6 and TNF-alpha, these changes
      were serum independent, while IL-10 was serum dependent. This response is
      different from LPS treated Kupffer cells where all three cytokines showed serum
      dependency. Overall, these data suggest that Kupffer cell stimulation by CEA is
      under beta-adrenergic receptor control and induction of the beta-receptor is an
      early event following CEA binding to its receptor. Control of TNF-alpha
      production is negatively affected by terbutaline, while that of IL-6 and IL-10 is
      positively controlled suggesting that very different beta-adrenergic receptor
      signaling pathways are involved.

PMID- 15159030
TI  - Novel therapeutics for treatment of long-QT syndrome and torsade de pointes.
AB  - Long-QT syndrome is a clinically and genetically heterogeneous syndrome
      characterized by lengthening of the QT interval and increased dispersion of the
      ventricular repolarization on surface electrocardiogram and a propensity to
      malignant ventricular arrhythmias, torsade de pointes and ventricular
      fibrillation, which may lead to sudden cardiac death. Long-QT syndrome mostly
      affects adolescents and young adults with structurally and functionally normal
      hearts and is caused by aberrations in potassium and sodium ion channels.
      Standard therapies for long-QT syndrome include correction of the underlying
      cause, alleviation of the precipitating factors, magnesium sulfate,
      isoproterenol, antiadrenergic therapy (beta-adrenergic receptor blockers, left
      cervicothoracic sympathectomy), cardiac pacing, and implantable cardioverter
      defibrillator. The potential therapies include sodium channel blockers
      (mexiletine, flecainide, lidocaine, pentisomide, phenytoin), potassium, potassium
      channel activators (nicorandil, pinacidil, cromakalim), alpha-adrenergic receptor
      blockers, calcium channel blockers, atropine, and protein kinase inhibitors. The
      purpose of this review is to outline the established therapies and update the
      recent advances and potential future strategies in the treatment of long-QT
      syndrome and torsade de pointes.

PMID- 15159031
TI  - Elucidating the B bump on the mitral valve M-mode echogram in patients with
      severe left ventricular systolic dysfunction.
AB  - BACKGROUND: The B bump on mitral valve M-mode echogram is predictive of
      significant elevation of left ventricular end-diastolic pressure (LVEDP).
      However, its pathophysiologic mechanism remains unclear. METHODS: We
      investigated, by means of Doppler echocardiography, the hemodynamic events that
      take place at late diastole in left atrium (LA) and left ventricle (LV). The
      study group consisted of 10 consecutive and strictly selected patients with
      severe dilated LV dysfunction. The noninvasive validated index used for
      definition of high LVEDP was the difference between the durations of atrial
      reverse (AR) wave in pulmonary venous flow (PVF) and atrial (A) wave in mitral
      flow (MF). Peak velocities of PVF and MF were measured. The time interval from
      ECG P wave to the end of B bump (P-B) and from P wave to the end of AR (P-AR)
      were measured and correlated. Mitral diastolic regurgitation (DR) was searched
      with M-mode color Doppler. RESULTS: All patients presented with restrictive
      diastolic signs on MF and PVF. The mean value of AR time minus A time was 61+/-12
      ms. There was a strong linear correlation between P-B and P-AR (r=0.94, p<0.001).
      Only five patients had DR. No patient had LV inflow during B bump. CONCLUSIONS:
      (1) Mitral B bump is essentially a late diastolic phenomenon in which the
      leaflets keep a semi-open position without LV inflow effectiveness. (2) The
      resultant LA pressure which prolongates the duration of AR wave beyond A wave,
      analogously work over mitral leaflets, pushing them toward LV generating the
      bump. (3) DR is caused by LVEDP higher than LA pressure and coexists with B bump
      without a cause-effect relationship.

PMID- 15159032
TI  - Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic
      shock.
AB  - OBJECTIVE: The objectives of this study were to determine myocardial injury in
      patients with septic shock by measuring serum cardiac troponin I (cTnI), to
      evaluate relationship between elevated cTnI and myocardial dysfunction and to
      determine if cTnI is a predictor of outcome in these patients. METHODS: Thirty
      seven consecutive patients with septic shock were included in the study. Serum
      cTnI was measured at study entry and after 24 and 48 h. Transthoracic
      echocardiogram, electrocardiogram and regular biochemical and hemodynamic
      assessments were performed. RESULTS: Sixteen (43%) patients had elevated serum
      cTnI. These patients had higher need for inotropic/vasopressor support (94% vs.
      53%, p=0.018), higher APACHE II score (28 vs. 20, p=0.004), higher incidence of
      regional wall motion abnormalities on echocardiography (56% vs. 6%, p=0.002),
      lower ejection fraction (46% vs. 62%, p=0.04) and higher mortality (56% vs. 24%,
      p=0.04) compared to normal cTnI patients. By multiple logistic regression
      analysis, serum cTnI and APACHE II score were independent predictor of death and
      length of stay in intensive care unit. Serum cTnI, APACHE II score, anion gap and
      serum lactate were independent predictor of need for inotropic/vasopressor
      support. Receiver-operating characteristics of serum cTnI as a predictor of death
      in septic shock were significant. The elevated serum level of cTnI correlated
      with the lower left ventricular ejection fraction (p<0.001). CONCLUSIONS:
      Myocardial injury can be determined in patients with septic shock by serum cTnI.
      Serum cTnI concentration correlates with myocardial dysfunction in septic shock.
      High serum cTnI predicts increased severity of sepsis and higher mortality. A
      close monitoring of patients with septic shock and elevated levels cTnI is
      warranted.

PMID- 15159033
TI  - Heart rate dynamics during three forms of meditation.
AB  - OBJECTIVE: This study was designed to quantify and compare the instantaneous
      heart rate dynamics and cardiopulmonary interactions during sequential
      performance of three meditation protocols with different breathing patterns.
      BACKGROUND: We analyzed beat-to-beat heart rate and continuous breathing signals
      from 10 experienced meditators (4 females; 6 males; mean age 42 years; range 29
      55 years) during three traditional interventions: relaxation response, breath of
      fire, and segmented breathing. RESULTS: Heart rate and respiratory dynamics were
      generally similar during the relaxation response and segmented breathing. We
      observed high amplitude, low frequency (approximately 0.05-0.1 Hz) oscillations
      due to respiratory sinus arrhythmia during both the relaxation response and
      segmented breathing, along with a significantly (p<0.05) increased coherence
      between heart rate and breathing during these two maneuvers when compared to
      baseline. The third technique, breath of fire, was associated with a different
      pattern of response, marked by a significant increase in mean heart rate with
      respect to baseline (p<0.01), and a significant decrease in coherence between
      heart rate and breathing (p<0.05). CONCLUSIONS: These findings suggest that
      different meditative/breathing protocols may evoke common heart rate effects, as
      well as specific responses. The results support the concept of a "meditation
      paradox," since a variety of relaxation and meditative techniques may produce
      active rather than quiescent cardiac dynamics, associated with prominent low
      frequency heart rate oscillations or increases in mean resting heart rate. These
      findings also underscore the need to critically assess traditional frequency
      domain heart rate variability parameters in making inferences about autonomic
      alterations during meditation with slow breathing.

PMID- 15159036
TI  - Monitoring of atherosclerosis.
AB  - Population-based epidemiological studies of atherosclerosis using autopsy
      material is now impossible to perform in most countries due to declining autopsy
      rates. Based on epidemiological studies of atherosclerosis using autopsy material
      in five European cities which were carried out with an interval of 25 years in
      the 1960s and 1980s, respectively, we have shown that atherosclerosis in young so
      called practically healthy people, 20-39 years of age, who died from accidental
      causes, closely reflects the level of atherosclerosis in the population as a
      whole. These people can thus be used for monitoring the development of
      atherosclerosis in a population since they are normally a subject to a medico
      legal autopsy; therefore, material for such studies can be obtained. Furthermore,
      histomorphological studies of specimens that are taken from practically healthy
      people at standard places of coronary arteries and aortas also reflect this
      general level of atherosclerosis. These studies also provide information on the
      atherosclerotic process and its relation to various risk factors.

PMID- 15159034
TI  - Intracoronary radiotherapy with a (188)rhenium liquid-filled PTCA balloon system
      in in-stent restenosis: acute and long-term angiographic results, as well as 1
      year clinical follow-up.
AB  - BACKGROUND: Intracoronary radiotherapy with beta- and gamma-emitters has been
      shown to reduce the risk of restenosis after balloon angioplasty and after
      coronary stenting. The present study addresses the question whether intracoronary
      radiotherapy using the (188)rhenium liquid-filled PTCA balloon system is
      feasible, safe and effective in cases of in-stent restenosis. Acute and long-term
      angiographic results as well as clinical events within 1 year after the procedure
      were evaluated. METHODS AND RESULTS: From September 1999 to April 2000, 41
      patients (mean age 60+/-10 years, 33 male, 8 female) with symptomatic in-stent
      restenosis underwent repeat PTCA and immediate intracoronary brachytherapy. After
      successful repeat PTCA (residual stenosis less than 30% in diameter), a second
      standard PTCA catheter was inflated with liquid (188)rhenium in the redilated in
      stent restenosis for 315-880, mean 540+/-155 s with low pressure (3 atm) in order
      to reach 30 Gy at 0.5 mm depth of the vessel wall. In all patients with
      successful reintervention, intracoronary radiotherapy was unproblematically
      performed; in 16 patients, 21 new stents were implanted during the procedure
      either immediately before or after radiation therapy. During follow-up, four
      episodes of stent thrombosis with subsequent myocardial infarction occurred in
      three patients (8 days, 37 days, 5 months and 6 months after the procedure,
      respectively). This complication was seen exclusively in patients with newly
      implanted stents. One patient of the stent group died suddenly 46 days after the
      procedure. All 40 surviving patients underwent repeat angiography in cases of
      repeat angina or routinely 6 months after brachytherapy, respectively. In the
      redilated target vessels without new stenting, restenosis (stenosis >50% in
      diameter) or reocclusion was observed in only 5 of 25 (=20%) cases, but in the
      restented target lesions, in 10 of 15 (=67%). Event-free survival (death,
      myocardial infarction, TVR) at 1 year after repeat dilatation and subsequent
      brachytherapy was 80% for patients not newly stented, but only 44% for patients
      with new stents. CONCLUSIONS: Intracoronary radiation therapy with the liquid
      filled beta-emitting (188)rhenium balloon is a safe and effective therapy in
      cases of in-stent restenosis. The positive effect of irradiation, however, is
      abolished if a new stent is needed. In the not newly stented patients, 1-year
      follow-up is encouraging.

PMID- 15159035
TI  - To what extent are the effects of diet on coronary heart disease lipid-mediated?
AB  - BACKGROUND: Cohort and case-control studies support the effect of diet on
      coronary heart disease. The objective of this study was to analyze the strength
      of the influence of dietary fat subtypes and other nutrients on serum lipids
      levels in patients with a first acute myocardial infarction. METHODS: We studied
      139 patients with a first myocardial infarction and no previous history of
      vascular disease. Serum lipids were determined, and nutrient intake was analyzed
      using a validated 118-food item questionnaire. RESULTS: Multiple regression
      models found weak but significant associations between the intake of different
      fatty acids and total to HDL cholesterol ratio (atherogenic index) when we
      adjusted for age, gender and body mass index (BMI). Positive associations with
      serum HDL cholesterol concentration were observed for energy-adjusted intake of
      red wine, alcohol intake, and omega-3 fatty acids intake. However, these
      nutrients explained less than 12% of the variability in the atherogenic index,
      and less than 17% in the variability of HDL. CONCLUSIONS: Our results suggest
      only a modest contribution of the investigated nutrients on serum lipids
      (atherogenic index and HDL cholesterol) in coronary patients. Alternative
      mechanisms of dietary factors not directly related with serum lipids or, more
      likely, a global effect of diet on inflammatory and antioxidant parameters should
      be studied in order to better understand the nature of dietary habits' influence
      on cardiovascular disease.

PMID- 15159037
TI  - Efficacy of internal cardioversion for chronic atrial fibrillation in patients
      with and without left ventricular dysfunction.
AB  - Internal cardioversion can restore sinus rhythm with energies below 6-10 J, often
      without anaesthesia/sedation. We investigated its safety and short-/medium-term
      efficacy in patients with persistent atrial fibrillation (AF) with left
      ventricular dysfunction (defined as ejection fraction < or = 40%). Among 34
      patients with persistent AF who agreed to receive internal cardioversion, 16 had
      left ventricular dysfunction and 18 did not (the groups were similar as regards
      age, duration of AF and pretreatment with amiodarone). Internal CV was performed
      delivering 3.0/3.0-ms biphasic shocks between coil catheters using a step-up
      protocol. Sinus rhythm was always restored. General anaesthesia (administered
      only when discomfort was not tolerated) was required only in 2 of the 16 (12.5%)
      patients with left ventricular dysfunction. The defibrillation threshold was
      similar in patients with and without left ventricular dysfunction (10.2+/-6.9 vs.
      8.4+/-4.9 J; p=0.37). Short-term (within 72 h) AF recurrence rates in the
      presence and absence of left ventricular dysfunction were 19% (3/16) and 6%
      (1/18), respectively (p=0.51). After cardioversion, all patients received
      antiarrhythmic drugs (mostly amiodarone in patients with left ventricular
      dysfunction and class IC agents in the remainder). With mean follow-up periods of
      about 220 days, AF recurrence rates among patients with and without left
      ventricular dysfunction were 50% (8/16) and 28% (5/18), respectively (p=0.328).
      We conclude that even in patients with left ventricular dysfunction, internal CV
      is safe and effective, minimizing risks from anaesthesia. Although these patients
      may have a higher risk of short- or medium-term AF recurrence, 6-month
      maintenance of sinus rhythm is possible in about 50% of cases.

PMID- 15159038
TI  - Brain natriuretic peptide kinetics during dynamic exercise in patients with
      chronic heart failure.
AB  - BACKGROUND: The kinetics of brain natriuretic peptide (BNP) secretion in chronic
      heart failure (CHF) during dynamic exercise have been the subject of
      controversial debate. The present study was therefore aimed to further clarify
      whether marked changes in BNP levels occur during and directly after vigorous
      exercise in CHF patients. METHODS: We prospectively studied 37 patients with CHF
      (60+/-10 years, LVEF 26+/-6%) and 20 healthy controls (58+/-11 years, LVEF 60+/
      3%). Standardized exercise testing was performed in all CHF patients and
      controls. Venous blood samples for measurement of BNP were obtained prior to
      symptom-limited exercise, at peak exercise and at 1 and 5 min of recovery time.
      RESULTS: BNP concentrations were significantly higher in CHF compared to controls
      at rest, peak exercise and at 1 and 5 min of recovery. BNP levels did not change
      significantly during exercise in the control group. In CHF patients, BNP levels
      showed no marked difference at rest (428+/-421 pg/ml), peak exercise (507+/-450
      pg/ml, n.s.), 1 min (560+/-460 pg/ml, n.s.) and 5 min recovery (526+/-424 pg/ml,
      n.s.). Strikingly, 6 of 37 CHF patients (16%) showed a decrease in BNP at
      exercise compared to rest but none of the controls. CONCLUSIONS: BNP levels in
      CHF patients and healthy controls are not significantly altered by vigorous
      exercise. In contrast to controls, 16% of CHF patients showed a decrease in BNP
      levels at exercise. In CHF, BNP levels were inversely correlated with peak VO(2),
      VO(2)-AT and LVEF.

PMID- 15159039
TI  - A comparison of HDL and LDL cholesterol for prevalent coronary calcification.
AB  - BACKGROUND: Coronary calcification is a marker for coronary atherosclerosis. It
      has been postulated that high levels of high density lipoprotein cholesterol (HDL
      C) are associated with a reduced amount of atherosclerotic disease while previous
      reports have found a lack of association between low density lipoprotein
      cholesterol (LDL-C) and coronary calcification (CAC). The purpose of this study
      was to compare the correlation and predictive power of HDL-C with LDL-C for
      prevalent coronary calcification. METHODS: A total of 6093 subjects were studied
      with respect to coronary calcification, serum cholesterol indices, personal
      health history and body morphology. Analyses consisted of correlation
      coefficients, logistic regression and sensitivity analysis to determine the
      strength of association between HDL-C and coronary calcification after
      controlling for covariates. RESULTS: The correlation between HDL-C and coronary
      calcium score (CCS) was three times that of LDL-C. Individuals with an HDL-C
      level <40 mg/dl had significantly higher calcium scores while increases in HDL-C
      were associated with a significant reduction in risk for the presence of any
      calcified plaque. Results of multivariate logistic regression revealed that HDL-C
      is predictive of calcified plaque development independent of LDL-C. Sensitivities
      and positive predictive values for both HDL-C and LDL-C were low. CONCLUSIONS:
      Increasing levels of HDL-C were associated with less coronary calcification and a
      smaller probability of having any calcified disease supporting the
      antiatherogenic hypothesis for HDL-C. HDL-C predicts the presence of any
      calcified atherosclerotic plaque independently of LDL-C. However, neither
      parameter seems suitable as a screening tool for predicting prevalent calcified
      atheromatous disease.

PMID- 15159040
TI  - On-line intracardiac echocardiography alone for Amplatzer Septal Occluder
      selection and device deployment in adult patients with atrial septal defect.
AB  - BACKGROUND: During the last few years, several different devices have been
      proposed for atrial septal defect (ASD) percutaneous closure. For the Amplatzer
      Septal Occluder (ASO) device, accurate balloon sizing is considered of paramount
      importance because the prosthesis waist has to be exactly adjusted to the defect
      diameter (+/-1 mm). In this study, we aimed to demonstrate the possibility of
      marked misinterpreting of the actual defect size using the balloon technique in
      patients with secundum ASD and to evaluate the accuracy of intracardiac
      echocardiography (ICE) measurements as a new method for selecting the size of ASO
      device. METHODS: Between February 1999 and December 2000, 166 consecutive adult
      patients underwent percutaneous transvenous secundum ASD occlusion using the ASO
      device. In 124 patients (control group), ASD were closed by conventional methods.
      In 13 patients (pilot group), balloon pulling technique was used in size
      selection, whereas ICE was used on-line to monitor device placement and off-line
      to assess its possibilities for accurate quantitative measurements and
      qualitative evaluation. In 31 patients (study group), ICE was used as the sole
      imaging tool both for guiding device selection and monitoring the procedure. All
      patients underwent complete transthoracic echocardiographic study before
      discharge and during follow-up visits at 3 and 12 months. RESULTS: Successful
      device implantation was accomplished in 163 of the 166 patients (98.2%). Short
      term follow-up results were available in all eligible patients at least 3 months.
      Complete occlusion was demonstrated in 91.4% and 92.2% of patients in the control
      and pilot groups, respectively, increasing to 97.3% in the study group (p<0.01
      vs. both control and pilot groups). There were no significant differences in mean
      ASO diameters in the control and pilot groups (20+/-7.7 and 22+/-5.4 mm,
      respectively), whereas the mean size of the devices used in the study group was
      significantly larger (27.4+/-6.2 mm, p<0.01 vs. both control and pilot groups).
      In the pilot group, the underestimation effect of the balloon strategy was
      evident, with a mean 12.3% larger diameter required on ICE measurements.
      Moreover, a misalignment between the ASO and the atrial septum was seen on ICE in
      9 of 13 patients of the pilot group, whereas good apposition of the ASO on the
      septum secundum was seen in all patients of the study group. CONCLUSION: ICE is a
      safe and effective method for selecting ASO size and continuous monitoring of the
      procedure. In contrast to the previously reported implantation procedure (device
      to-defect ratio 1:1), a device 10-20% larger than invasively measured stretched
      defect diameter should be chosen and implanted on the basis of the ICE data.

PMID- 15159041
TI  - Effects of smoking on nitric oxide synthesis in epicardial normal and
      atheromatous coronary arteries.
AB  - The effects of an intracoronary infusion of N(G)-monomethyl-L-arginine (LNMMA)
      followed by intracoronary administration of nitroglycerin in non-stenotic
      proximal and distal coronary segments were studied in 11 patients with coronary
      artery disease and in 19 subjects with "normal arteriograms". In normal subjects,
      LNMMA induced significant constriction (p<0.01) of proximal and distal vessels in
      non-smokers and smokers. In normal non-smokers, the reduction in coronary luminal
      diameter of proximal segments was significantly greater compared to normal
      smokers (p<0.05). In patients with coronary artery disease, LNMMA induced
      significant constriction of proximal and distal vessels in smokers, and only
      distal constriction in non-smokers (p<0.01). The reduction in coronary luminal
      diameter of the distal segments in normal smokers, and in both groups in patients
      with coronary artery disease was significantly greater compared with proximal
      segments (p<0.05). Therefore, the difference in vasomotor response to LNMMA in
      relation to smoking is localised to the proximal coronary segments.

PMID- 15159042
TI  - A novel method for the detection of transient myocardial ischaemia using body
      surface electrocardiac mapping.
AB  - BACKGROUND: The limitations of the 12-lead ECG in the detection of myocardial
      ischaemia are well known. This study sought to test the hypothesis that a Body
      Surface Mapping (BSM) system can detect and localise the transient regional
      ischaemia induced by elective percutaneous coronary intervention (PCI) in
      patients with stable angina. METHODS AND RESULTS: 25 patients undergoing elective
      single vessel PCI were studied: 11 with RCA lesions, 9 with LAD lesions and 5
      with circumflex lesions. Patients had BSM readings every 30 s following the
      inflation of a dilating balloon in the target vessel for 1 min. BSMs were
      analysed for ST segment change at 60 ms after the J point (ST60). Peak ST changes
      were analysed and colour map reconstruction made. Characteristic ST segment
      changes in each arterial domain were observed following inflation of the balloon.
      Maximal change occurred in a standard V lead on only 2/46 occasions.
      Statistically significant rapid rise and fall of ST 60 readings were observed
      indicating the onset recovery and location of the transient ischaemia. A novel
      method for the presentation of colour map reconstruction that removes baseline
      noise has been developed. CONCLUSIONS: These data confirm the hypothesis that
      this BSM system can detect and display transient myocardial ischaemia. BSM may
      represent a novel clinical tool for the assessment of clinical ischaemia.

PMID- 15159044
TI  - Hemolysis parameters of St. Jude Medical: Hemodynamic Plus and Regent valves in
      aortic position.
AB  - BACKGROUND: Elevated plasma lactate dehydrogenase (LDH) concentration may reflect
      hemolysis due to mechanical heart valve dysfunction. Thus, knowledge of LDH
      levels in patients with properly working prostheses is required. Because
      hemolysis parameters for the SJM Hemodynamic Plus (HP) and Regent series are
      currently not available, the purpose of our study was to determine these data.
      METHODS: At 12-19 months follow-up after isolated aortic valve replacement with
      SJM HP(R) or Regent prostheses, we examined 102 patients by transthoracic
      echocardiography and determined plasma LDH, haptoglobin, bilirubin and
      hemoglobin. RESULTS: Five patients with properly working prostheses were excluded
      because of increased LDH due to non-cardiac reasons. In four patients with
      paravalvular leakage, LDH was 244, 307, 446 and 628 U/l, respectively. In
      patients with properly working prostheses, LDH was 287+/-52 (range: 163-374) U/l
      for HP(R) (n=33) and 274+/-48 (151-386) U/l for Regent valves (n=60, p=0.2).
      Haptoglobin was <1g/l in all patients; in 91% of HP and 75% of Regent valves,
      haptoglobin was below detection limit. Bilirubin and hemoglobin as well as red
      blood cell count (RBC) were normal in all patients except for five patients with
      renal anemia, two patients with paravalvular leakage and four patients with
      macrocytosis due to alcohol abuse. There was no correlation between LDH and
      transvalvular gradient (r=-0.02) or valve size (r=0.25). CONCLUSIONS: In patients
      with SJM HP(R) or Regent valves in aortic position, LDH values > 400 U/l indicate
      valvular dysfunction or leakage if non-cardiac causes for hemolysis are excluded.
      However, paravalvular leakage can be present without substantially increased LDH.
      Haptoglobin has no diagnostic value as it is almost always markedly reduced.
      Hemolysis does not correlate with transvalvular gradient or prosthesis size.

PMID- 15159043
TI  - Activation of coagulation occurs after electrical cardioversion in patients with
      chronic atrial fibrillation despite optimal anticoagulation with warfarin.
AB  - BACKGROUND: There is evidence for the activation of the coagulation system and a
      hypercoagulable state following cardioversion. The aim of the study was to
      determine whether electrical cardioversion in patients with chronic atrial
      fibrillation induced a prothrombotic state despite optimal anticoagulation. We
      studied the effects of electrical cardioversion on plasma levels of fibrinogen,
      antithrombin III, protein C and D-dimers. METHODS: We studied 24 patients with
      chronic atrial fibrillation who were on optimal anticoagulation and were referred
      for electrical cardioversion. Samples of venous blood were taken 2 h pre and post
      cardioversion and 1 month later. RESULTS: Plasma median concentrations of
      fibrinogen decreased significantly from 3.8 g/l (interquartile range 3.1-4.2 g/l)
      before cardioversion to 3.5 g/l (interquartile range 2.9-3.9 g/l) 2 h after
      cardioversion levels (P=0.004). The fibrinogen levels at 1 month post
      cardioversion (3.45 g/l, interquartile range 3.1-3.9 g/l) were also significantly
      lower than baseline (P=0.02). Plasma median levels of antithrombin III fell from
      93.5 U/dl (interquartile range 89.3-97.0 U/dl) pre cardioversion to 89.5 U/dl
      (interquartile range 83.0-93.0 U/dl) 2 h after cardioversion (P=0.001) and
      returned to normal by 1 month (94.0 U/dl; interquartile range 89.3-98.5 U/dl;
      P=0.0001). There were no significant changes in plasma median D-dimer or protein
      C levels at any time. CONCLUSIONS: We have demonstrated a significant fall in the
      plasma fibrinogen and antithrombin III levels in patients with chronic atrial
      fibrillation early after electrical cardioversion, indicating thrombin
      generation. This study suggests that there are haemostatic changes of
      thrombogenesis induced by cardioversion despite optimal anticoagulation with
      warfarin.

PMID- 15159045
TI  - Chlamydia pneumoniae infection is associated with coronary artery disease but not
      implicated in inducing plaque instability.
AB  - BACKGROUND: Many authors have shown an association between Chlamydia pneumoniae
      (C. pneumoniae) infection and coronary artery disease. However, whether C.
      pneumoniae infection plays an important role in triggering an acute coronary
      event remains to be elucidated. METHODS: Sixty-four consecutive patients with
      unstable angina (group A), 56 consecutive patients with stable exertional angina
      (group B) and 74 control subjects (group C) were studied. The IgM, IgG and IgA
      anti-C. pneumoniae titers were assessed (microimmunofluorescence test Labsystem),
      values > or =1:16, > or =1:32 and > or =1:16 being respectively considered
      positive. RESULTS: IgM antibodies were found in 10.9% of group A and 12.5% of
      group B patients, whereas no subject of group C showed IgM titers (A vs. B, p=ns;
      C vs. A and B, p<0.05). Positive IgG titers were found in 76.6%, 82% and 44.6% in
      groups A, B and C, respectively (A vs. B, p=ns; C vs. A and B, p<0.05). Positive
      IgA titers were found in 62.5%, 61% and 31.1% in groups A, B and C, respectively
      (A vs. B, p=ns; C vs. A and B, p<0.05). Acute infection was observed in 10.9% and
      12.5% of patients in groups A and B, respectively (p=ns); reinfection in 17% and
      11%; no patient of the control group had signs of acute infection or reinfection.
      Chronic infection was observed in 34.4% and 37.5% in group A and B, respectively
      (p=ns). CONCLUSION: C. pneumoniae infection is associated with coronary artery
      disease, but no difference in serology is present between unstable and stable
      angina. Therefore, it does not seem implicated in triggering an acute coronary
      event.

PMID- 15159046
TI  - Sinus node function after cardiac surgery: is impairment specific for the maze
      procedure?
AB  - BACKGROUND: Maze surgery is a final solution for intractable atrial fibrillation
      (AF), but an adverse effect on postoperative sinus node function has been
      reported. Whether this also applies to other types of cardiac surgery is unclear.
      METHODS: We assessed postoperative rhythm by means of repeated exercise tolerance
      testing, ambulatory electrocardiography, and non-invasive testing of autonomic
      function between 1 and 12 months after four types of cardiac surgery. Fourteen
      patients without structural cardiac disease and medically refractory AF underwent
      the maze III procedure, 11 patients with mitral valve disease and preoperative AF
      underwent valvar surgery combined with a (simplified) maze III procedure, and 8
      patients with mitral valve disease in sinus rhythm (SR) underwent isolated valvar
      surgery. The control group consisted of eight patients with sinus rhythm who
      underwent coronary artery bypass surgery (CABG). RESULTS: One month after
      surgery, the chronotropic response to exercise was depressed, mean heart rate was
      high, and heart rate variability (HRV) was low, especially after maze III,
      combined surgery, and isolated valvar surgery. Twelve months after surgery,
      moderate improvements were observed. After CABG, considerably fewer abnormalities
      were observed, and HRV parameters recovered to a large extent. Non-invasive
      testing of autonomic function indicated disturbed vagal modulation of heart rate
      in all three groups with atrial incision. CONCLUSION: Thus, attenuation of HRV
      and vagal modulation of sinus node function are not confined to maze surgery but
      also apply to isolated mitral valve surgery. Atrial incision therefore appears to
      be crucial and presumably produces autonomic nervous damage followed by partial
      reinnervation. Nevertheless, cardiac surgery in general seems initially to impair
      sinus node function with partial recovery in the consecutive 12 months.

PMID- 15159047
TI  - Can cardiac vagal tone be estimated from the 10-second ECG?
AB  - BACKGROUND: Heart rate variability (HRV) recorded over 5 min or 24 h is used
      increasingly to measure autonomic function and as a prognostic indicator in
      cardiology. Measuring HRV during a standard 10-s ECG would save time and cut
      costs. The aim of this study, therefore, was to discover whether indices of HRV
      calculated over 10 s could predict cardiac vagal tone (CVT) recorded over a 5-min
      period by the NeuroScope, a new instrument that selectively measures vagal tone.
      METHODS: A total of 50 subjects had ECGs taken at the beginning, middle and end
      of a 5-min measurement of CVT. Standard deviation of normal-to-normal RR interval
      (SDNN), root mean square of successive differences in RR intervals (rMSSD), and
      the average absolute difference (AAD) in RR intervals were calculated from RR
      intervals derived from the ECGs. Subjects were divided into a training set (n=40)
      and a test set (n=10). RESULTS: Regression equations derived from the training
      set predicted 5-min mean CVT in the test set with r(2) of 95.8%, 92.9% and 87.9%
      for AAD, rMSSD and SDNN, respectively. Indices obtained from the third ECG in
      each set tended to give a closer relationship with CVT than those derived from
      the first and second ECGs: this could be because of the greater spread of the
      independent variables in the third set. An underlying linear physiological
      phenomenon could not be excluded, however, without continuing the measurements
      over a longer time. CONCLUSIONS: These results demonstrate that AAD and rMSSD
      calculated from a 10-s ECG can accurately predict 5-min mean CVT as measured by
      the NeuroScope.

PMID- 15159048
TI  - Impacts of 17beta-estradiol, including environmentally relevant concentrations,
      on reproduction after exposure during embryo-larval-, juvenile- and adult-life
      stages in zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) were exposed for 3 weeks to low concentrations of
      estradiol including environmentally relevant concentrations (5, 25 and 100 ng/l),
      encompassing either their embryo-larvae (from fertilization to 21 day post
      fertilization (dpf)), juvenile (from 21 to 42 dpf) or adult life stages (>200
      dpf) with a view to investigating the most sensitive life stage of the zebrafish
      to 17beta-estradiol (E2). At all sampling points, whole-body vitellogenin
      concentrations and gonadal development were analyzed in order to investigate the
      effects of estrogen exposure on these endpoint in the zebrafish. In the adult
      stage, additional endpoints were measured including secondary sexual
      characteristics (manifestation of the uro-genital papillae (UGP) in males),
      gonadal growth (the gonado-somatic index (GSI)) and sex ratio. For all the
      different life stage exposures, reproductive performance of the F0 generation was
      assessed (egg production) and survival and development of the F1 embryo-larvae.
      Exposure to low concentrations of E2 resulted in vitellogenin induction whatever
      the life stage exposed but these effects were reversible after depuration. The
      effective concentration for vitellogenin induction in zebrafish early life stages
      was 100 ng E2/l, and in adult male zebrafish the effective concentration for
      vitellogenin induction (between 5 and 25 ng/l) was lower than for the early life
      stage fish. Exposure to E2 prior to (from fertilization to 21 dpf) and during the
      time of sex differentiation (from 21 to 42 dpf) also caused disruptions in the
      process of sexual differentiation (resulting in formation of a retrogonadal
      cavity in presumptive male, germ cell development and leading to a significant
      change of the sex ratio towards the female sex at the dose of 100 ng E2/l for the
      fish exposure as embryo-larvae) and altered patterns of egg production in the
      subsequent adults. Exposure of adult fish to E2 resulted in a modification of the
      secondary sexual characteristic in males at 25 and 100 ng E2/l as well as a dose
      dependent inhibition of egg production. The findings from this study show that
      the nature and intensity of the reproductive effects of E2 are dependent of the
      time and concentration of exposures of zebrafish to E2, some of these effects
      being permanent (effect on the sexual differentiation) while others being
      reversible (effect on the Vtg induction). This study demonstrated that early life
      stages of zebrafish are sensitive to low concentrations of E2 and provides
      relevant data that could be used for the adaptation of existing fish early life
      stage test for the in vivo testing of estrogenic compounds. The data presented
      raise further concerns about the effects of steroid estrogens in the environment
      on fish reproductive health.

PMID- 15159049
TI  - Unprecedented genomic diversity of AhR1 and AhR2 genes in Atlantic salmon (Salmo
      salar L.).
AB  - Aryl hydrocarbon receptor (AhR) genes encode proteins involved in mediating the
      toxic responses induced by several environmental pollutants. Here, we describe
      the identification of the first two AhR1 (alpha and beta) genes and two
      additional AhR2 (alpha and beta) genes in the tetraploid species Atlantic salmon
      (Salmo salar L.) from a cosmid library screening. Cosmid clones containing
      genomic salmon AhR sequences were isolated using a cDNA clone containing the
      coding region of the Atlantic salmon AhR2gamma as a probe. Screening revealed 14
      positive clones, from which four were chosen for further analyses. One of the
      cosmids contained genomic AhR sequences that were highly similar to the rainbow
      trout (Oncorhynchus mykiss) AhR2alpha and beta genes. SMART RACE amplified two
      complete, highly similar but not identical AhR type 2 sequences from salmon cDNA,
      which from phylogenetic analyses were determined as the rainbow trout AhR2alpha
      and beta orthologs. The salmon AhR2alpha and beta encode proteins of 1071 and
      1058 residues, respectively, and encompass characteristic AhR sequence elements
      like a basic-helix-loop-helix (bHLH) and two PER-ARNT-SIM (PAS) domains. Both
      genes are transcribed in liver, spleen and muscle tissues of adult salmon. A
      second cosmid contained partial sequences, which were identical to the previously
      characterized AhR2gamma gene. The last two cosmids contained partial genomic AhR
      sequences, which were more similar to other AhR type 1 fish genes than the four
      characterized salmon AhR2 genes. However, attempts to amplify the corresponding
      complete cDNA sequences of the inserts proved very difficult, suggesting that
      these genes are non-functional or very weakly transcribed in the examined
      tissues. Phylogenetic analyses of the conserved regions did, however, clearly
      indicate that these two AhRs belong to the AhR type 1 clade and have been
      assigned as the Atlantic salmon AhR1alpha and AhR1beta genes. Taken together,
      these findings demonstrate that multiple AhR genes are present in Atlantic salmon
      genome, which likely is a consequence of previous genome duplications in the
      evolutionary past of salmonids. Plausible explanations for the high incidence of
      AhR genes in fish and more specifically in salmonids, like rapid divergences in
      specialized functions, are discussed.

PMID- 15159050
TI  - Reduction of cytochrome P4501A with age in Atlantic tomcod from the St. Lawrence
      Estuary, Canada: relationship with emaciation and possible effect of
      contamination.
AB  - This study reports a reduction of ethoxyresorufin-O-deethylase (EROD) activity in
      large-sized, older Atlantic tomcod (Microgadus tomcod) collected in the St.
      Lawrence Estuary (Quebec, Canada) and investigates its relationship over a 4-year
      period to sex, gonadosomatic index (GSI), condition factor (CF) and cytochrome
      P4501A (CYP1A) mRNA levels. In addition, the concentrations of polychlorinated
      biphenyls (PCBs) were measured in a subsample of fish. The reduction of EROD
      activity with age was observed each year in both sexes and was not related to the
      GSI. A high proportion of large-sized fish, with a body length greater or equal
      to 225 mm, were emaciated (CF < or = 0.55). A 6-16-fold reduction of EROD
      activity and a 2-4-fold reduction of CYP1A mRNA levels were observed in large
      sized emaciated females compared to small-sized non-emaciated females.
      Concentrations of PCBs in liver increased from 1000 to 4000 ng/g lipid weight as
      the hepatic lipid content and the CF decreased. The inter-annual variation of
      EROD activity was associated with the variation in CF with lowest EROD activity
      and CF in 1999. When emaciated fish were excluded from the analyses, EROD
      activity was still lower (2-5-fold) in large compared to small fish and was no
      longer related to CF. For similar levels of CYP1A mRNA, EROD activity was lower
      in large compared to small fish. Thus, there was post-transcriptional inhibition
      of CYP1A activity in large-sized tomcod, indicative of cellular dysfunction. This
      response may be related to aging, chronic exposure to toxic contaminants or to
      selective pressures favoring less responsive individuals. This study demonstrates
      that fish age, size, and CF are important variables to consider in studies using
      EROD activity as an indicator of environmental contamination. The main finding
      was that a large part of the reduction of CYP1A with age in St. Lawrence Estuary
      tomcod was associated with severe emaciation of a large proportion of large-sized
      fish. Hepatic concentrations of contaminants covaried with the CF and the effects
      of these two variables on CYP1A could not be discriminated.

PMID- 15159051
TI  - Effects of prolonged copper exposure in the marine gulf toadfish (Opsanus beta).
      I. Hydromineral balance and plasma nitrogenous waste products.
AB  - Acute (96 h) and prolonged (30 days) copper exposure induced osmoregulatory
      disturbance and impaired nitrogenous waste excretion in the marine teleost, the
      gulf toadfish (Opsanus beta), which was found to be extremely tolerant to acute
      copper exposure with a 96 h LC50 exceeding 340 microM but exhibited disturbed
      mineral balance in response to both acute and prolonged exposure to approximately
      12 microM copper. The main cause of copper toxicity was found to be Na+ and Cl-
      regulatory failure leading to elevated plasma [Na+] and [Cl-] and osmolality
      which in turn led to fluid loss from muscle tissue. Analysis of intestinal fluid
      composition revealed a complicated pattern of effects of copper exposure.
      Intestinal transport physiology was directly influenced by copper exposure with
      Cl- absorption being the most sensitive parameter. Evidence for increased Na+ and
      fluid absorption when the fish exhibited elevated plasma osmolality indicates
      that the intestine may also exhibit a compensatory response to impairment of
      branchial transport processes, suggesting at least two target organs (gill and
      intestine) for copper toxicity in marine fish. Plasma Mg2+ was elevated from
      approximately 1.5 mM to as much as 4.0 mM, likely as a result of increased
      branchial permeability. While plasma [ammonia] clearly responded to copper
      exposure, plasma [urea] exhibited a much more sensitive and pronounced response
      to both acute and prolonged copper exposure, resulting in as much as a three-fold
      increase in circulating urea levels. This response is most likely the result of
      the unique ability of this teleost to convert ammonia to urea.

PMID- 15159054
TI  - Proceedings and abstracts of the XXth International Complement Workshop.
      Honolulu, Hawaii, USA. June 13-18, 2004.

PMID- 15159052
TI  - Effects of prolonged copper exposure in the marine gulf toadfish (Opsanus beta)
      II: copper accumulation, drinking rate and Na+/K+ -ATPase activity in
      osmoregulatory tissues.
AB  - Gulf toadfish were exposed to sublethal levels of copper (12.8 or 55.2 microM)
      for 30 days. Drinking in control fish averaged 1 ml kg(-1)h(-1) but exposure to
      55.2 microM copper resulted in a complex biophasic pattern with initial (3 h and
      1 day) inhibition of drinking rate, followed by an elevation of drinking rate
      from day 3 onwards. Drinking led to copper accumulation in the intestinal fluids
      at levels three to five times higher than the ambient copper concentrations,
      which in turn resulted in intestinal copper accumulation. The gill exhibited more
      rapid accumulation of copper than the intestine and contributed to early copper
      uptake leading to accumulation in internal organs. Muscle, spleen and plasma
      exhibited little if any disturbance of copper homeostasis while renal copper
      accumulation was evident at both ambient copper concentrations. The liver
      exhibited the highest copper concentrations and the greatest copper accumulation
      of all examined internal organs during exposure to 55.2 microM. Elevated biliary
      copper excretion was evident from measurements of gall bladder bile copper
      concentrations and appeared to protect partially against internal accumulation in
      fish exposed to 12.8 microM copper. No inhibition of Na+/K+ -ATPase activity in
      either gills or intestine was seen despite copper accumulation in these organs.
      Calculations of inorganic copper speciation suggest that Cu(CO3)(2)2- complexes
      which dominate in seawater and intestinal fluids are of limited availability for
      uptake while the low levels of ionic Cu2+, CuOH+ and CuCO3 may be the forms taken
      up by the gill and the intestinal epithelium.

PMID- 15159053
TI  - Androgenic and estrogenic effects of the synthetic androgen 17alpha
      methyltestosterone on sexual development and reproductive performance in the
      fathead minnow (Pimephales promelas) determined using the gonadal recrudescence
      assay.
AB  - The effects of the androgen, 17alpha-methyltestosterone were assessed on sexual
      development and reproductive performance in the fathead minnow (Pimephales
      promelas) using a gonadal recrudescence assay. In this assay, mature male and
      female fathead minnow, previously kept under simulated winter conditions (15
      degrees C; 8:16 h light:dark regime) were transferred to simulated summer
      conditions (25 degrees C water temperature; 16:8 h light:dark regime) to induce
      gonadal recrudescence. To assess sexual development fish were exposed to nominal
      concentrations of 0, 0.1, 1, 5 and 50 microg/L 17alpha-methyltestosterone. After
      3 weeks of chemical exposure, effects on condition (condition factor, CF), plasma
      vitellogenin (VTG), secondary sex characteristics, gonad growth (gonadosomatic
      index; GSI) and gonad histology were investigated. Reproductive performance,
      including reproductive output (egg production), spawning behaviour, and
      fertilisation rate were measured over a subsequent 3-week-period in breeding
      adults maintained in clean water. 17alpha-Methyltestosterone had no effects on
      the condition of fish at any of the doses tested. 17alpha-Methyltestosterone
      induced both androgenic and estrogenic effects with females generally more
      affected by 17alpha-methyltestosterone than males: atretic follicles and male
      specific sex characteristics (androgenic effect) were induced in females at > or
      = 0.1 and > or = 1 microg/L 17alpha-methyltestosterone, respectively. An
      inhibitory effect on ovary growth occurred at an exposure concentration of 50
      microg/L 17alpha-methyltestosterone. In males 1 microg/L 17alpha
      methyltestosterone induced a concentration-response induction of plasma
      vitellogenin (estrogenic effect) likely due to its conversion into 17alpha
      methylestradiol, rather to the competition with endogenous steroids and their
      cross reactivity with the estrogen receptor. In the fish breeding studies,
      concentration-dependent reductions in egg number, fertilisation rate and
      increases in abnormal sexual behaviour in females were observed. All of these
      effects occurred at exposure concentrations of > or = 5 microg/L 17alpha
      methyltestosterone. Thus, it could be assumed that the observed estrogenic
      effects in male fathead minnow were likely to the conversion of 17alpha
      methyltestosterone into the estrogen 17alpha-methylestradiol, rather to the
      acting of 17alpha-methyltestosterone itself. In conclusion to this, showing
      hormonally activity of 17alpha-methyltestosterone in fish down to 100 ng/L,
      indicates that its potency was close to the range of several naturally occurring
      estrogens.

PMID- 15159055
TI  - Primitive complement system--recognition and activation.
AB  - The complement system, composed of more than 30 serum and cell surface
      components, is collaborating in recognition and elimination of pathogens as a
      part of both the innate and acquired immune systems. The two collagenous lectins,
      mannose-binding lectin (MBL) and ficolins, are one of the pattern recognition
      molecules acting in innate immunity and upon recognition of the pathogens, they
      trigger the activation of the lectin complement pathway through attached serine
      proteases (MASPs). A similar lectin-base complement system, consisting of the
      lectin-protease complex and C3, is present in ascidians, our closest invertebrate
      relatives and functions in an opsonic manner. On the other hand, ongoing genome
      projects in both vertebrates and invertebrates revealed that most domains used by
      mammalian complement components are found in both protostomes and deuterostomes.
      However, the unique combinations of them as found in mammalian complement
      components are present only in deuterostomes, indicating the deuterostome origin
      of the complement system. Unexpectedly, the complement system of an invertebrate
      deuterostome, ascidian, shows a similar level of complexity as that of mammals,
      suggesting that expansion of complement genes by gene duplications occurred
      independently both in the ascidian and vertebrate lineages. Although most
      characteristic domain structures of the mammalian complement components are found
      in ascidians, detailed evolutionary analysis casts doubt on their mutual
      reactivity in several points. Thus, another integrative step seems to have been
      required to establish the modern complement system of higher vertebrates.

PMID- 15159056
TI  - Mannan-binding lectin--a soluble pattern recognition molecule.
AB  - The immune system must discriminate between self and non-self. Mannan-binding
      lectin (MBL) is a recognition molecule able to differentiate between the
      carbohydrates found on self glycoproteins and the carbohydrate patterns found on
      infectious non-self surfaces. It exists in a complex with MBL-associated serine
      proteases (MASPs). When MBL binds to suitable carbohydrate pattern it causes
      activation of MASPs leading to triggering of the complement cascade. This results
      in limiting the infection and the orchestration of subsequent adaptive immune
      response. The plasma concentration of MBL is determined by genetic polymorphisms.
      Deficiency of MBL is a risk factor for infection, especially when other functions
      in the immune system are also compromised. MBL has a potential to react against
      altered-self structures, as found on apoptotic cells, cancers or ischemic
      reperfused tissue. The focus of the current review is to summarize the recent
      progress in our understanding of MBL functions.

PMID- 15159057
TI  - The anaphylatoxins bridge innate and adaptive immune responses in allergic
      asthma.
AB  - The complement system has long been recognized for its role as a lytic effector
      system that protects against microbial pathogens, as well as for its role in
      mediating acute and chronic inflammatory responses. Many of the inflammatory
      sequelae of complement activation can be related to the complement cleavage
      fragments C3a and C5a, the so-called anaphylatoxins (ATs). Cloning and subsequent
      gene targeting of their corresponding receptors, as well as generation of
      specific C3a and C5a inhibitors, have fueled new interest in studies aimed at
      defining the roles of the anaphylatoxins in inflammatory diseases. Traditionally,
      the anaphylatoxins have been considered mediators of end-stage effector
      mechanisms. However, recent data from animal models of allergic asthma suggest
      that C3a and C5a provide a critical link between innate and adaptive immunity.
      This review is aimed at outlining our current knowledge of when and where
      anaphylatoxins contribute to and control the development of allergic asthma. The
      accumulated data suggest a model in which C3a and C5a play important but opposing
      roles during allergen-induced T-cell polarization: C3a promotes Th2 responses,
      whereas C5a prevents Th2 polarization. During the effector phase, both
      anaphylatoxins trigger the inflammatory response and contribute to
      bronchoconstriction.

PMID- 15159058
TI  - Dendritic cells and complement: at the cross road of innate and adaptive
      immunity.
AB  - The interaction between different components of the immune system plays a pivotal
      role in the overall development of immune responses. Dendritic cells (DCs) and
      complement are essential components of innate immunity. They have been shown to
      be relevant both in the induction of adaptive immune responses and in maintenance
      of tolerance. However, hyperactivity of these systems has also been demonstrated
      to be detrimental in various disease states. Despite increased insight into
      dendritic cell biology, relatively little is known about possible interactions
      between dendritic cells and complement. This review focuses on novel findings,
      which have started to shed light on these intriguing components of the innate
      immune system.

PMID- 15159059
TI  - The complement system in B cell regulation.
AB  - Early studies of animals bearing natural deficiencies in complement C3 and C4 and
      mice transiently deficient in C3 suggested that the complement system played a
      role in humoral immunity. Identification and characterization of the complement
      receptors CD21 and CD35 and their expression on B lymphocytes provided evidence
      for a direct role for complement in "linkage of innate and adaptive immunity".
      More recent studies of mice bearing targeted deficiencies in complement proteins
      C3, C4 or the receptors CD21/CD35 has confirmed the importance of complement in B
      cell responses in vivo and extended our understanding to distinct stages in B
      cell differentiation in which complement participates in humoral immunity. In
      this review, a role for complement is described in five distinct stages of B cell
      differentiation.

PMID- 15159060
TI  - The alternative pathway of complement in disease: opportunities for therapeutic
      targeting.
AB  - The alternative pathway of complement is receiving increasing attention as a
      therapeutic target because of recent findings in several animal models that
      support its essential role in tissue injury and disease pathogenesis. Although
      the contribution of alternative pathway activation to serum complement activation
      in vitro is relatively modest, its role in generating activated pro-inflammatory
      fragments at extra-vascular sites is substantial. Several potential mechanisms
      might underlie this exaggerated effect, including local synthesis of alternative
      pathway components, disease-induced alterations of regulatory proteins, and
      influx of inflammatory cells that contain alternative pathway components into
      sites of injury. This review examines several animal models in which the
      alternative pathway is centrally involved in disease pathogenesis and which
      suggest a potential role for alternative pathway inhibitors as therapies for
      human disease. It is also expected that several clinically relevant studies will
      be presented at the XXth International Complement Workshop that will identify
      additional areas of interest with regard to this pathway.

PMID- 15159061
TI  - From atoms to systems: a cross-disciplinary approach to complement-mediated
      functions.
AB  - With an ever-increasing wealth of information made available to researchers from
      expanding genomic sequence and protein structure databases, traditional
      experimentation and research are being drastically revisited. The unidirectional
      study of single molecules and pathways is being replaced by a combinatorial and
      cross-disciplinary platform that investigates interactive biological systems and
      dynamic networks. The complement system constitutes an ideal paradigm of how this
      concept is being applied in the field of contemporary immunology. Our laboratory
      has adopted such a cross-disciplinary approach in elucidating key aspects of
      complement functions and determining the role of several complement proteins in
      both inflammatory and developmental processes. Here we discuss recent findings
      pertaining to the rational development of complement inhibitors, our studies on
      protein-protein interactions and our progress in the study of viral immune
      evasion and complement evolution. Furthermore, we present recent studies
      implicating complement components in complex developmental processes, such as
      organ regeneration, hematopoietic development, and stem cell engraftment.

PMID- 15159062
TI  - Initiation of complement activation following oxidative stress. In vitro and in
      vivo observations.
AB  - Ischemia and reperfusion of organs/tissues induce a state of inflammation that
      can lead to tissue injury. Focus on development of effective therapeutics based
      on sound pre-clinical work and the role of leukocytes in models of human disease
      has not lead to a successful clinical trial for anti-leukocyte technologies. For
      the past >30 years, it has been known that complement activation plays a role in
      the inflammation and tissue injury associated with ischemia/reperfusion (I/R)
      injury. In the last 10 years, several complement inhibitors have made their way
      from the bench to bedside. Will a complement inhibitor eventually be approved for
      clinical treatment of I/R type diseases? What pathway(s) are involved in I/R
      injury, and what role do they play? What specific complement components are
      needed for resolution of inflammation and what components need to be inhibited to
      decrease tissue injury? This short review will focus on the current state of the
      art knowledge about complement, complement pathways, complement components and
      several promising clinical biologics that inhibit complement activation. This
      review is not a complete review of complement in ischemia/reperfusion injury, but
      it raises important questions about the role of complement, its pathways and the
      current knowledge in the area of ischemia/reperfusion injury.

PMID- 15159063
TI  - cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding
      cellular proteins involved in inflammation and infection.
AB  - The first component of complement, C1, is a multi-molecular complex comprising of
      C1q and the Ca(2+)-dependent tetramer C1r(2)-C1s(2). The traditional role of C1q
      within the complex is that of recognition signal-a signal, which is instantly
      converted into a highly specific intramolecular proteolytic activation of the
      C1r(2)-C1s(2) tetramer thereby triggering activation of the classical pathway.
      Another important function of C1q is its ability to bind to a wide range of cell
      types resulting in the induction of cell-specific biological responses. These
      cells include polymorphonuclear leukocytes, monocytes, lymphocytes, dendritic
      cells, endothelial cells and platelets. Interaction of C1q with endothelial cells
      and platelets, for example, leads to cellular activation followed by release of
      biological mediators and/or expression of adhesion molecules, all of which
      contribute, directly or indirectly to the inflammatory process. These specific
      responses are mediated by the interaction of C1q with C1q binding proteins or
      receptors on the cell surface. To date, four types of putative C1q binding cell
      surface expressed proteins/receptors have been described. These include cC1q
      R/CR, or calreticulin (CR), a 60 kDa protein, which is also known as collectin
      receptor; gC1q-R/p33, a 33 kDa homotrimeric protein; C1q-Rp (CD93), a 120 kDa, O
      sialoglycoprotein; and CR1 (CD35), the receptor for C3b. Although the specific
      role of each of these molecules in a given C1q-mediated cellular response is yet
      to be worked out, all of them may, in one form or another, participate in the
      inflammatory processes associated with vascular or atherosclerotic lesions,
      autoimmune diseases, or infections. The main focus of our laboratory for the past
      20 years has been to elucidate the structure and function of cC1q-R/CR and gC1q
      R/p33, both of which have been isolated and characterized on the basis of their
      ability to bind C1q. The purpose of this article is therefore to provide an up to
      date overview of these two proteins with particular emphasis on their unique
      structural and functional features, their multi-faceted nature and most
      importantly their role in infection and inflammation.

PMID- 15159065
TI  - Recombinant cobra venom factor.
AB  - Cobra venom factor (CVF) is the complement-activating protein from cobra venom.
      CVF is a three-chain protein that functionally resembles C3b, the activated form
      of complement component C3. Like C3b, CVF forms a C3/C5 convertase with factor B
      in the presence of factor D and Mg(2+). Although CVF exhibits functional activity
      of C3b, it structurally resembles the C3b degradation product C3c, which is not
      able to form a C3/C5 convertase. CVF has become an important research tool to
      decomplement laboratory animals in order to study the role of complement in host
      defense, immune response, and pathogenesis of disease. As the Asian cobras of the
      Naja species are on the list of endangered species, cobra venom as the source for
      CVF has become increasingly difficult to obtain. Methods have been developed to
      recombinantly produce active forms of CVF. This manuscript reviews the production
      of recombinant pro-CVF using both prokaryotic and eukaryotic expression systems.
      The recombinant production of pro-CVF in two insect cell expression systems
      (baculovirus-infected Sf9 Spodoptera frugiperda cells, stably transfected S2
      Drosophila melanogaster cells) generates three forms of pro-CVF: single-chain pro
      CVF resembling pro-C3, a two-chain form of pro-CVF resembling C3, and another two
      chain form of pro-CVF resembling C3b. All three forms of pro-CVF exhibit
      functional activity of mature, natural CVF. Recombinant pro-CVF supports the
      activation of factor B in the presence of factor D and Mg(2+), forms a
      bimolecular convertase pro-CVF,Bb that exhibits cleaving activity for both C3 and
      C5, and depletes the serum complement activity. The activity of pro-CVF and the
      resulting C3/C5 convertase is indistinguishable from CVF and the CVF,Bb
      convertase. Recombinant production of functionally active forms of pro-CVF
      ensures the availability of an important research reagent for future research
      involving complement depletion. The experimental systems to recombinantly produce
      active forms of CVF will also be invaluable for studies to delineate the
      structure/function relationship of CVF and its differences from C3, and to
      generate human C3 derivatives with CVF-like function ("humanized CVF") for
      therapeutic complement depletion.

PMID- 15159064
TI  - A role for lipid rafts in C1q-triggered O2- generation by human neutrophils.
AB  - Calreticulin, a candidate C1q receptor, was shown recently to be present on the
      surface of human neutrophils in association with glycosylphosphatidylinositol
      (GPI) anchored proteins, particularly CD59. In this study, we show that
      antibodies to CD59, as well as to every other GPI-anchored protein tested,
      inhibited the C1q-triggered release of O(2)(-) from PMN. Methyl beta cyclodextrin
      (M beta CD) treatment of the cells to disrupt lipid rafts also prevented C1q
      triggered O(2)(-) production. beta(2) integrin-dependent co-stimulation is
      required for O(2)(-) production from PMN, however M beta CD had no effect on LFA
      1 or Mac-1-mediated adhesion, soluble iC3b binding to PMN, or spreading and
      migration, all of which suggested that PMN integrin function remained intact.
      Flow cytometric analysis of PMN treated with M beta CD showed upregulation of PMN
      granule-associated integrins and a corresponding increase in integrin activation
      reporter epitopes, in contrast to the decreased expression of GPI-anchored
      antigens. These data support a model where lipid rafts and their associated GPI
      anchored proteins are critical for C1q-triggered O(2)(-) production, consistent
      with a model where calreticulin serves as the C1q receptor for O(2)(-) production
      from PMN.

PMID- 15159066
TI  - Sexual abuse and suicidal behavior.

PMID- 15159067
TI  - Sexual abuse and suicidality: gender differences in a large community sample of
      adolescents.
AB  - OBJECTIVE: A cross-sectional study of gender specific relationships between self
      reported child sexual abuse and suicidality in a community sample of adolescents.
      METHOD: Students aged 14 years on average (N = 2,485) from 27 schools in South
      Australia completed a questionnaire including items on sexual abuse and
      suicidality, and measures of depression (Centre for Epidemiological Studies
      Depression Scale), hopelessness (Beck Hopelessness Scale), and family functioning
      (McMaster Family Assessment Device General Functioning Subscale). Data analysis
      included logistic regression. RESULTS: In boys, self-report sexual abuse is
      strongly and independently associated with suicidal thoughts, plans, threats,
      deliberate self-injury, and suicide attempts, after controlling for current
      levels of depression, hopelessness, and family dysfunction. In girls, the
      relationship between sexual abuse and suicidality is mediated fully by
      depression, hopelessness, and family dysfunction. Girls who report current high
      distress about sexual abuse, however, have a threefold increased risk of suicidal
      thoughts and plans, compared to non-abused girls. Boys who report current high
      distress about sexual abuse have 10-fold increased risk for suicidal plans and
      threats, and 15-fold increased risk for suicide attempts, compared to non-abused
      boys. Fifty-five percent (n = 15) of sexually abused boys attempted suicide
      versus 29% (n = 17) girls. CONCLUSIONS: A history of sexual abuse should alert
      clinicians, professionals and carers in contact with adolescents, to greatly
      increased risks of suicidal behavior and attempts in boys, even in the absence of
      depression and hopelessness. Distress following sexual abuse, along with
      depression and hopelessness indicate increased risk of suicidal behavior in
      girls, as well as boys.

PMID- 15159068
TI  - The effects of child sexual abuse in later family life; mental health, parenting
      and adjustment of offspring.
AB  - OBJECTIVE: To investigate links between child sexual abuse (occurring before 13
      years), later mental health, family organization, parenting behaviors, and
      adjustment in offspring. METHOD: The present study investigates a subsample of
      the Avon Longitudinal Study of Parents and Children an ongoing study of women and
      their families in the area of Avon, England. A sample of 8292 families met
      inclusion criteria for identifiable family type and completed self-report data on
      prior sexual assault. Further data were collected on life course variables,
      socioeconomic variables, psychological well-being, relationship quality, parent
      child relationship quality, and children's adjustment. RESULTS: After adjustment
      for other childhood adversity, prior child sexual abuse was associated with a
      range of outcomes in adulthood, including current membership of a nontraditional
      family type (single mother and stepfather) poorer psychological well-being,
      teenage pregnancy, parenting behaviors, and adjustment problems in the victim's
      later offspring. The relationship of child sexual abuse with aspects of the
      parent-child relationship in later life and with the offspring's adjustment
      difficulties were mediated in part by mother's mental health--chiefly anxiety.
      CONCLUSION: Findings indicate that child sexual abuse has long-term repercussions
      for adult mental health, parenting relationships, and child adjustment in the
      succeeding generation.

PMID- 15159069
TI  - Risk behaviors and resiliency within physically abused adolescents.
AB  - OBJECTIVE: This study examines the relationship between physical abuse and
      several risk behaviors, and thriving behaviors, and the relationship between
      potential protective factors and engagement in risk and thriving behaviors among
      victims of physical abuse. Three categories of potential protective factors were
      examined: (1) individual characteristics, (2) family processes, and (3) extra
      familial factors. We expected that high levels of protective factors would reduce
      engagement in risk behaviors (i.e., alcohol use, tobacco use, drug use, sexual
      activity, antisocial behavior, attempted suicide, and purging) among abused
      adolescents. RESULTS: Across all the risk behaviors, abused adolescents reported
      a higher frequency of engagement than non-abused adolescents. Several protective
      factors were identified for the seven risk behaviors. Peer group characteristics
      was a significant predictor in all seven of the logistic regressions, followed by
      positive school climate (six models), religiosity (five models), other adult
      support (five models), family support (four models), view of the future (two
      models), and involvement in extra-curricular activities (two models). The
      variance accounted for by the models ranged from 2% (risk behavior of purging) to
      26% (risk behavior of alcohol use and antisocial behavior). CONCLUSIONS: The
      findings indicate that, with the exception of sexual activity, the majority of
      abused adolescents were not engaging in risk behaviors; however, significantly
      more abused adolescents were engaging in risk behaviors than their non-abused
      counterparts. In addition, that protective factors were found to exist at various
      levels of the adolescents' ecology has strong implications for practice.

PMID- 15159070
TI  - Associations between types of maltreatment and substance use during adolescence.
AB  - OBJECTIVE: The aim of this study was to investigate associations between four
      categories of maltreatment and substance use among adolescents. METHOD: All 10th
      through 12th graders n = 2,187) at six public high schools in a rural Oregon
      county filled out an anonymous survey that included questions about their
      experience of emotional, sexual, and physical abuse and their use of a variety of
      substances. Substance use was subsequently categorized as: (1) tobacco use, (2)
      alcohol use, and (3) illicit drug use. Experience of maltreatment was
      subsequently categorized as: (1) no type of maltreatment, (2) emotional abuse,
      (3) physical abuse, (4) sexual abuse, and (5) sexual and physical abuse. RESULTS:
      Results showed that all four categories of maltreatment were associated with
      increased levels of all three categories of substance use. Statistical
      comparisons of the magnitude effects of different types of maltreatment on
      substance use indicated a linear trend with the effects of emotional abuse being
      significantly lower than those of physical or sexual abuse, and the effects of
      the combination of physical and sexual abuse being significantly higher than the
      other types. CONCLUSION: Results suggested that all types of maltreatment,
      including emotional abuse, are related to significantly higher levels of
      substance use and should be considered serious risk factors for substance use
      during adolescence. Results also indicated that the strength of association
      between maltreatment and substance use varies by type of maltreatment. Youth who
      have experienced both physical and sexual abuse are at especially high risk of
      substance use.

PMID- 15159071
TI  - The impact of individual forms of childhood maltreatment on health behavior.
AB  - OBJECTIVE: This study examines the unique contribution of five types of
      maltreatment (sexual abuse, physical abuse, emotional abuse, physical neglect,
      emotional neglect) to adult health behaviors as well as the additive impact of
      exposure to different types of childhood maltreatment. METHOD: Two hundred and
      twenty-one women recruited from a VA primary care clinic completed questionnaires
      assessing exposure to childhood trauma and adult health behaviors. Regression
      models were used to test the relationship between childhood maltreatment and
      adult health behaviors. RESULTS: Sexual and physical abuse appear to predict a
      number of adverse outcomes; when other types of maltreatment are controlled,
      however, sexual abuse and physical abuse do not predict as many poor outcomes. In
      addition, sexual, physical, and emotional abuse and emotional neglect in
      childhood were all related to different adult health behaviors. The more types of
      childhood maltreatment participants were exposed to the more likely they were to
      have problems with substance use and risky sexual behaviors in adulthood.
      IMPLICATIONS: The results indicate that it is important to assess a broad
      maltreatment history rather than trying to relate specific types of abuse to
      particular adverse health behaviors or health outcomes.

PMID- 15159072
TI  - In vitro effect of nanoleakage expression on resin-dentin bond strengths analyzed
      by microtensile bond test, SEM/EDX and TEM.
AB  - This study evaluated the effect of multiple consecutive adhesive resin coatings
      of adhesive bonded to human dentin on nanoleakage and resin-dentin bond strength.
      Resin bonded dentin specimens were prepared using a total-etch adhesive (One-Step
      Plus) applied as multiple consecutive coating, or using two self-etch adhesive
      systems (iBond or Fluoro Bond). For the total-etch adhesive, resin application
      and air evaporation were performed 1, 2, 3, or 4 times. The self-etch adhesives
      were applied according to manufacturers' instructions. Resin-dentin bonded beams
      were prepared and immersed in water (control) or ammoniacal silver nitrate. After
      storage, microtensile bond strengths were measured. The fractured surfaces were
      examined by scanning and transmission electron microscopy (SEM and TEM), and
      energy-dispersive X-ray spectrometry (EDX). No significant differences in bond
      strength were found between water and silver nitrate storage groups. Several
      types of silver depositions (spotted, reticular, or water trees) were found in
      adhesive joints. The bond strengths of the single coated specimens of the total
      etch adhesive were significantly lower than those receiving 2-4 coatings. Single
      coats produced more nanoleakage than multiple coats. However, no correlation was
      found between the bond strengths and nanoleakage between the different adhesives
      (total-etch adhesive with different conditions or self-etch adhesives).

PMID- 15159073
TI  - Biomimetic growth of apatite on hydrogen-implanted silicon.
AB  - Hydrogen in silicon has been widely applied in semiconductor fields. In this
      paper, the application of hydrogen-implanted silicon wafer in biomedical fields
      was explored by investigating its bioactivity. Hydrogen implanted silicon wafers
      were prepared using plasma immersion ion implantation. The surface structures of
      the 1.4 x 10(17) cm(-2) hydrogen-implanted silicon wafers were investigated using
      atomic force microscopy and transmission electron microscopy (TEM). The hydrogen
      depth profiles were acquired by SIMS and the crystal quality of the as-implanted
      silicon was studied by channeling Rutherford backscattering spectrometry (RBS).
      The bioactivity of the implanted silicon was evaluated using the biomimetic
      growth of apatite on its surface after it was soaked in simulated body fluid for
      a period of time. The TEM, SIMS and RBS results indicate the formation of an
      amorphous hydrogenated silicon (a-Si:Hx) layer has been formed on the surface of
      the hydrogen-implanted silicon wafer. After immersion in SBF for 14 days, bone
      like apatite is observed to nucleate and grow on the surface. With longer soaking
      time, more apatite appeared on the surface of the hydrogen implanted silicon but
      our control experiments did not reveal any apatite formation on the surface of
      the un-implanted silicon wafer, hydrogenated crystalline silicon wafer (with
      hydrogen, but no amorphous surface), or argon-implanted silicon wafer (amorphous
      surface but without hydrogen). Our results indicated that the bioactivity of
      silicon wafer can be improved after hydrogen implantation and the formation of
      the amorphous hydrogenated silicon (a-Si:Hx) surface also plays a synergistic
      role to improve the bioactivity.

PMID- 15159074
TI  - Histomorphometric, ultrastructural and microhardness evaluation of the
      osseointegration of a nanostructured titanium oxide coating by metal-organic
      chemical vapour deposition: an in vivo study.
AB  - Over the past decade the increase of elderly population has determined a rise in
      the incidence of bone fractures, and the improvement of the implant-bone
      interface remains an open problem. Metal-organic chemical vapour deposition
      (MOCVD) has recently been proposed as a technique to coat orthopaedic and dental
      prostheses with metal nanostructured oxide films either through the decomposition
      of oxygenated compounds (single-source precursors) or the reaction of oxygen-free
      metal compounds with oxygenating agents. The present study was performed to
      assess the in vivo biocompatibility of commercially pure Ti (control material:
      TI/MA) implants ( psi 2 mm x 5 mm length) coated with nanostructured TiO2 films
      by MOCVD (Ti/MOCVD) and then inserted into rabbit femoral cortical
      (middhiaphysis) and cancellous (distal epiphysis) bone. Histomorphometric,
      ultrastructural and microhardness investigations were carried out. Four and 12
      weeks after surgery, significant (p<0.0005) increases in AI of Ti/MOCVD implants
      were observed as compared to Ti/MA implants (distal femoral epiphysis: 4
      weeks=8.2%, ns; 12 weeks=52.3%, p <0.005; femoral diaphysis: 4 weeks=20.2%, p
      <0.0005; 12 weeks=10.7%, p <0.005). Bone microhardness results showed significant
      increases for the Ti/MOCVD versus Ti/MA implants at 200 microm in the femoral
      diaphysis (4 weeks=14.2, p <0.005) and distal femoral epiphysis (12 weeks=14.5, p
      <0.01) at 4 and 12 weeks, respectively. In conclusion, the current findings
      demonstrate that the nanostructured TiO2 coating positively affects the
      osseointegration rate of commercially pure Ti implants and the bone
      mineralization at the bone-biomaterial interface in both cortical and cancellous
      bone.

PMID- 15159075
TI  - Biocompatibility of poly(epsilon-caprolactone)/poly(ethylene glycol) diblock
      copolymers with nanophase separation.
AB  - In this study, we prepared diblock copolymers of poly(epsilon-caprolactone) (PCL)
      and poly(ethylene glycol) (PEG) by aluminum alkoxide catalysts. The biological
      responses to the spin cast surface of different PCL/PEG diblock copolymers were
      investigated in vitro. Our results showed that surface hydrophilicity improved
      with the increased PEG segments in diblock copolymers and that bacteria adhesion
      was inhibited by increased PEG contents. PCL-PEG 23:77 showed nanotopography on
      the surface. The number of adhered endothelial cells, platelets and monocytes on
      diblock copolymer surfaces was inhibited in PCL-PEG 77:23 and enhanced in PCL-PEG
      23:77. Nevertheless, the platelet and monocyte activation on PCL-PEG 23:77 was
      reduced. PCL-PEG 23:77 had better cellular response as well as lower degree of
      platelet and monocyte activation. The current study was the first one to
      demonstrate that surface nanotopography could influence not only cell adhesion
      and growth but also platelet and monocyte activation.

PMID- 15159076
TI  - In vitro biocompatibility assessment of poly(epsilon-caprolactone) films using
      L929 mouse fibroblasts.
AB  - Biodegradable and biocompatible materials are the basis for tissue engineering.
      As an initial step for developing vascular grafts, the in vitro biocompatibility
      of poly(epsilon-caprolactone) (PCL), recently suggested for several clinical
      applications, was evaluated in this study using L929 mouse fibroblasts. Different
      cellular aspects were analyzed in order to know the cell viability during cell
      culture on PCL films: adhesion, proliferation, morphology, LDH release and
      mitochondrial function. Since topography and other surface characteristics of
      materials play an essential part in cell adhesion, PCL membranes with either
      smooth or rough surface were prepared, characterized and used to carry out cell
      cultures. During short culture times, PCL produced a significant stimulation of
      mitochondrial activity evaluated by reduction of the MTT reagent. The results
      provide evidences of good adhesion, growth, viability, morphology and
      mitochondrial activity of cells on PCL films. Therefore, it can be concluded that
      PCL is a suitable and biocompatible material as a scaffold for vascular graft
      development.

PMID- 15159077
TI  - Immobilization of cell adhesive RGD peptide onto the surface of highly porous
      biodegradable polymer scaffolds fabricated by a gas foaming/salt leaching method.
AB  - A cell adhesive peptide moiety, Gly-Arg-Gly-Asp-Tyr (GRGDY), was immobilized onto
      the surface of highly porous biodegradable polymer scaffolds for enhancing cell
      adhesion and function. A carboxyl terminal end of poly(D,L-lactic-co-glycolic
      acid) (PLGA) was functionalized with a primary amine group by conjugating
      hexaethylene glycol-diamine. The PLGA-NH2 was blended with PLGA in varying ratios
      to prepare films by solvent casting or to fabricate porous scaffolds by a gas
      foaming/salt leaching method. Under hydrating conditions, the activated GRGDY
      could be directly immobilized to the surface exposed amine groups of the PLGA-NH2
      blend films or scaffolds. For the PLGA blend films, the surface density of GRGDY,
      surface wettability change, and cell adhesion behaviors were characterized. The
      extent of cell adhesion was substantially enhanced by increasing the blend ratio
      of PLGA-NH2 to PLGA. The level of an alkaline phosphatase activity, measured as a
      degree of cell differentiation, was also enhanced as a result of the introduction
      of cell adhesive peptides.

PMID- 15159078
TI  - The modulation of tissue-specific gene expression in rat nasal chondrocyte
      cultures by bioactive glasses.
AB  - Since bone repair may occur, following endochondral ossification, we have
      investigated the behaviour of chondrocytes isolated from nasal septum cartilage
      of foetal rats and cultured up to 21 days in the presence of a melt-derived
      bioactive glass (Bioglass 45S5) and a less reactive glass with 60 wt% silica
      content (60S). In both cultures, chondrocytes proliferate and form typical
      cartilaginous nodules on day 5 of cultures. However, on day 12, the nodules in
      contact with 45S5 granules became darker than in 60S cultures, corresponding to
      the emergence of matrix biomineralization. Transmission electron microscopy
      showed a collagen-rich matrix composed of densely packed fibres and mineralized
      foci formed of needle-shaped crystals in contact with an electron-dense layer
      located at the periphery of the material. The specific activity of alkaline
      phosphatase was significant higher in 45S5 cultures on day 15 than in 60S
      cultures. Real time RT-PCR was used to monitor gene expression levels of specific
      chondrogenic markers. The transcription factor Sox9 was expressed throughout the
      culture period, but with no significant differences between the two kinds of
      cultures. In contrast, Runx2 expression was higher in experiment cultures on day
      12. Type II collagen mRNA and aggrecan, showed an almost similar expression
      pattern with a strong expression at the beginning of cultures but higher in
      experiment cultures. Indian hedgehog was strongly expressed between day 9 and 12
      with a significant stimulation in 45S5 cultures. Similarly, type X collagen mRNA
      seemed to be up-regulated in 45S5 cultures on day 20. In conclusion, this study
      shows hat 45S5 Bioglass has the ability to support the growth of chondrocytes and
      to stimulate some chondrogenic molecular markers.

PMID- 15159080
TI  - Long-term culture of embryonic rat cardiomyocytes on an organosilane surface in a
      serum-free medium.
AB  - Potential applications of engineered, functional, cardiac muscle extends from
      basic research through drug discovery to engineering heart tissue for
      transplantation. One of the central questions in cardiac tissue engineering is to
      understand and control the complex interactions between the cardiac muscle cells
      and their environment. Recent progress in chemistry, material science, and cell
      biology have made possible the control of the extracellular environment (soluble
      factors and also cell-substrate signaling) in in vitro systems. In this study we
      report on the development of a defined system (artificial surface, serum-free
      medium combination, consistent cell preparation), which promotes the
      differentiation and long-term survival of rat embryonic cardiomyocytes. Cardiac
      muscle cells plated on a N-1 (3-(trimethoxysilyl) propyl) diethylenetriamine
      (DETA) surface in serum-free medium survived for more than 8 weeks in vitro and
      maintained their contractile and electrophysiological properties. Our methods are
      also compatible with advanced cell patterning techniques such as microcontact
      printing and photolithography which now could enable systematic spacial
      modifications to create growth substrates for the study of the role of contact
      signaling in cardiac myocyte development and physiology. It also provides a test
      bed for the long-term evaluation of soluble compounds such as toxins and drug
      candidates in a defined system.

PMID- 15159079
TI  - Global gene expression of cells attached to a tissue engineering scaffold.
AB  - A goal of tissue engineering is to produce a scaffold material that will guide
      cells to differentiate and regenerate functional replacement tissue at the site
      of injury. Little is known about how cells respond on a molecular level to tissue
      engineering scaffold materials. In this work we used oligonucleotide microarrays
      to interrogate gene expression profiles associated with cell-biomaterial
      interactions. We seeded collagen-glycosaminoglycan meshes, a widely used tissue
      engineering scaffold material, with human IMR-90 fibroblasts and compared
      transcript levels with control cells grown on tissue culture polystyrene. Genes
      involved in cell signaling, extracellular matrix remodeling, inflammation,
      angiogenesis and hypoxia were all activated in cells on the collagen-GAG mesh.
      Understanding the impact of a scaffold on attached cells will facilitate the
      design of improved tissue engineering materials.

PMID- 15159081
TI  - Controlling surface nano-structure using flow-limited field-injection
      electrostatic spraying (FFESS) of poly(D,L-lactide-co-glycolide).
AB  - Improved control of surface micro- and nano-structure may lead to enhanced
      performance of degradable biomedical devices such as surgical dressings, vascular
      grafts, tissue engineering scaffolds, sutures, and structures for guided tissue
      regeneration. An electrohydrodynamic method called flow-limited field-injection
      electrostatic spraying (FFESS) has been developed as an improved technique for
      the controlled deposition of polymeric material. Injecting charge using a nano
      sharpened tungsten needle in a process called field ionization can efficiently
      induce an ionic state in a solution of poly(D,L-lactide-co-glycolide) increasing
      its capacity to carry charge. As a result, sprays have been produced that are
      finer and more precisely controlled than sprays produced by conventional
      electrospraying techniques, which employ hypodermic needles as the spray nozzle.
      Here, the effect of FFESS variables including applied voltage, polymer solution
      flow rate, and solvent properties (surface tension, viscosity, vapor pressure) on
      spray performance have been qualitatively evaluated. Under certain conditions,
      increasing the applied voltage produced an increasingly rough surface morphology.
      Similarly, by reducing solvent surface tension and increasing solvent vapor
      pressure, more distinct surface structures could be formed including uniform
      nanoparticles. Working ranges of the important parameters for the production of
      specific structure types such as smooth or porous surfaces, non-woven or melded
      fibers, and distinct or melded nanoparticles have been defined. FFESS technology
      provides a simple yet powerful technique for fabricating biomedical devices with
      a precisely defined nano-structure potentially capable of utilizing a broad range
      of biocompatible polymeric materials.

PMID- 15159082
TI  - The effect of salt and pH on the phase-transition behaviors of temperature
      sensitive copolymers based on N-isopropylacrylamide.
AB  - The salt and pH effects on the phase transition behaviors of temperature
      sensitive hydrophilic and amphiphilic polymers containing copolymers of N
      isopropylacrylamide as hydrophilic segments were investigated by UV and dynamic
      light scattering studies. The polymers used for this study include two
      hydrophilic polymers of HO-terminated poly(N-isopropylacrylamide-co-N,N
      dimethylacrylamide) (1) and HO-functionalized poly(N-isopropylacrylamide-co-N
      hydroxylmethylacrylamide) (3), and their amphiphilic derivatives of poly(N
      isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide) (2) and
      cholesteryl-grafted poly(N-isopropylacrylamide-co-N-hydroxylmethylacrylamide)
      (4). With the increase of NaCl concentration, significant salt effects on their
      phase transition behaviors were observed. (1) Significant decreases in the lower
      critical solution temperatures of all polymers were observed, the salt effects
      were also characterized by a newly defined 'phase transition salt concentration';
      (2) time-course UV spectroscopic studies showed that the phase transitions became
      faster and more complete with the increase of NaCl concentration, which were
      demonstrated by a newly defined 'phase transition constant'; (3) the salt exerted
      stronger effects on phase transition behaviors of the amphiphilic polymers than
      that of the hydrophilic polymers, and on polymer 4 than polymer 2. In contrast,
      the phase transition behaviors of the polymers were less sensitive to pH. The
      present studies provide important information for the design and synthesis of
      temperature-sensitive polymers and polymeric micelles that are important drug
      delivery carriers for hydrophobic drugs.

PMID- 15159084
TI  - Relationship between triple-helix content and mechanical properties of gelatin
      films.
AB  - This paper reports a study on the influence of the renaturation level of gelatin
      on the mechanical and swelling properties of gelatin films. Films at different
      renaturation level were obtained from gelatin samples with different Bloom index.
      It was verified that the triple-helix content, calculated from the values of the
      enthalpy of denaturation associated to the endothermal transition at about 41
      degrees C of gelatin, increases with the Bloom index. The d.s.c. data are further
      supported by the results of the X-ray diffraction investigation carried out on
      the same samples. The increase of triple-helix content provokes a significant
      reduction in the degree of swelling, and a remarkable improvement of the
      mechanical properties of the films. The elastic Young's modulus, E, increases
      linearly with the renaturation level, from 3.6 to 12.0 MPa. Crosslinking with GTA
      1% remarkably reduces the degree of swelling of all the samples, and induces a
      further increase of the Young's modulus, which reaches values up to 27 MPa.

PMID- 15159083
TI  - Biocompatibility of NGF-grafted GTG membranes for peripheral nerve repair using
      cultured Schwann cells.
AB  - We previously developed a biodegradable composite with potentially good
      biocompatibility composed by tricalcium phosphate and gluataraldehyde cross
      linking gelatin (GTG) with good mechanical property feasible for surgical
      manipulation. The purpose of this study was to evaluate the feasibility of
      immobilizing nerve growth factor (NGF) onto the composite (GTG) with carbodiimide
      (GEN composite). Cultured Schwann cells were seeded onto the GTG and GEN
      composites. For comparison, GTG membrane soaked in NGF solution without
      carbodiimide (GN composite) as cross-linking agent was also used to culture
      Schwann cells. Cell morphology was observed by a scanning electron microscope.
      Cell survival, cytotoxicity and cellular metabolism on the NGF-grafted GTG
      membrane were assessed quantitatively in terms of cell protein content, leakage
      of cytosolic lactate dehydrogenase (LDH) activity and by the well-established MTT
      assay, respectively. The result of LDH study did not show significant difference
      among GTG, NGF-modified GTG and control group. This indicated that GTG composite,
      whether cross-linking with NGF or not, has little cytotoxic effect. Comparing the
      protein content and MTT assay among GEN, GN composite and control group, the data
      confirmed more attachment of Schwann cells on GEN composite. Although GTG cross
      linking with NGF did not promote Schwann cell proliferation, the techniques we
      used in this study provided a method to fabricate a novel biomaterial
      incorporation of Schwann cells and covalently immobilized NGF.

PMID- 15159085
TI  - Adolescents' experiences of parental employment and parenting: connections to
      adolescents' well-being.
AB  - This paper examines whether the relationship between parental work and
      adolescents' well-being would be mediated through parenting behaviour. The
      primary focus was on the experiences of adolescents. Questionnaire-based data
      from families (both parents and one children, n = 77) and adolescents (n = 126)
      were collected in Finland in 2000 and 2001, respectively. The adolescents were on
      average 14 years old. Results showed that the relationships between parents'
      negative work experiences and adolescents' depression (all perceived by
      adolescents) were partially mediated by adolescents' experience of lessened
      autonomy granting in parenting and increased conflicts between parents and
      adolescents. In addition, the relations between fathers' negative work
      experiences and adolescents' negative attitude regarding school (all reported by
      adolescents) were mediated by adolescents' perceptions of increased conflicts
      between fathers and adolescents.

PMID- 15159087
TI  - The reciprocal relationship between early adolescent attachment and internalizing
      and externalizing problem behaviour.
AB  - The aim of the present study is to examine the reciprocal relationship between
      parental attachment and adolescent internalizing and externalizing problem
      behaviour. In this longitudinal study, 288 adolescents (mean age 13.5 years)
      reported on their attachment relationships with their parents and on problem
      behaviour three times, with 1-year-intervals between measurement waves. Results
      show that attachment and both indicators of adolescent problem behaviour remain
      stable over time, although there were differences in stability between
      constructs. Reciprocal negative effects were found between attachment and
      internalizing problem behaviour, and between attachment and externalizing problem
      behaviour.

PMID- 15159086
TI  - Indices of lifetime polydrug use among adolescents.
AB  - The functional equivalency for three indices of lifetime polydrug use was
      examined in a sample of adolescents (N = 794). The following indices were
      included in analyses: (a) a count of lifetime self-report of substances used; (b)
      an index weighted by the severity of the substances used; and (c) a hierarchical
      index of substance use. Analyses for each index was conducted twice with
      abstinent youth (no report of substances over their lifetime) included and
      excluded from analyses. Relationships between the indices with gender, age,
      ethnicity, and country of origin were examined. The only difference between the
      indices found was for ethnicity in the full sample. African Americans had higher
      scores on the hierarchical substance use index than Latinos or Asian/Pacific
      Islanders. With the exception of the relationship between the hierarchical index
      and ethnicity, the relationships between the other demographic variables with
      indices were consistent. Implications for utilizing the count or weighted index
      versus a hierarchical index of lifetime polydrug use are discussed.

PMID- 15159088
TI  - Adolescent adjustment in a nationally collected sample: identifying group
      differences by adoption status, adoption subtype, developmental stage and gender.
AB  - The current study investigated group differences in adolescent adjustment by
      adoption status and adoption subtype in a national sample, in contrast to group
      differences based on developmental stage or gender. Secondary analyses of the
      National Longitudinal Study of Adolescent Health were performed to describe group
      differences in a broad range of adjustment measures (a) between adoptees and non
      adoptees, (b) between different-race adoptees and same-race adoptees and, (c)
      across adolescent developmental stage and gender groups. Based upon a
      developmental deviance hypothesis, the current study hypothesized that early
      adolescent different-race adoptees would fair better across measures of academic
      performance, familial relationships, psychological adjustment, and physical
      health than their middle and late adolescent counterparts. Group comparisons
      revealed little evidence of increased maladjustment among adopted adolescents
      compared to non-adopted study participants. In addition, group comparisons
      revealed few differences across indices of adolescent adjustment by adoption
      subtype (i.e. by the degree of racial congruence adopted child and adoptive
      parent). However, significant group differences in adolescent adjustment were
      found based on participants' developmental stage and gender. The implications of
      the findings are discussed.

PMID- 15159089
TI  - Adolescents' outcome expectancies about relational aggression within
      acquaintanceships, friendships, and dating relationships.
AB  - Adolescents' (N = 292) relational aggression and outcome expectancies for
      relational aggression in three different relationship contexts (acquaintanceship,
      friendship, and dating) were assessed. With respect to each type of relationship,
      adolescents were questioned about the emotional and dyadic consequences of
      relational aggression, and about whether the victim of relational aggression
      would retaliate. It was also of interest to assess whether adolescents' personal
      involvement in relational aggression was associated with these judgments. The
      results suggest that adolescents' involvement in relational aggression and
      outcome expectancies for relational aggression often varies by gender, age,
      relationship context, and type of relational aggression. Additionally, in several
      instances, adolescents' personal involvement in relational aggression was
      associated with outcome expectancies for relational aggression. For example,
      after gender and age had been accounted for, participants' own relational
      aggression predicted beliefs about whether the victim of relational aggression
      would want to continue a friendship and a dating relationship. Implications of
      the results and future directions for research are discussed.

PMID- 15159090
TI  - Adolescents define sexual orientation and suggest ways to measure it.
AB  - Researchers disagree on how to assess adolescent sexual orientation. The relative
      importance of various dimensions (e.g. attraction, relationships, behavior, self
      labeling) is unknown, which calls into question the validity of studies assessing
      adolescent sexual orientation. To address this issue, 50 male and female
      adolescents of varied sexual orientations participated in focus groups and
      interviews. Two types of sexual attraction-one a physiologic reaction and the
      other a cognitive response-were central to adolescent sexual orientation.
      Participants did not perceive sexual behavior and self-identification as
      necessarily relevant. Preliminary items to measure sexual attraction were
      developed based on these adolescents' perceptions.

PMID- 15159091
TI  - Youth engaging in online harassment: associations with caregiver-child
      relationships, Internet use, and personal characteristics.
AB  - To date, research focused on "traditional" (i.e. in-person) youth bullying
      behaviour has documented serious psychosocial challenges for those involved. How
      this literature translates to youth engaging in aggressive behaviours online has
      yet to be examined. Using the largest US sample of youth Internet users to date,
      psychosocial characteristics of youth engaging in Internet harassment were
      examined. Results from the nationally representative survey suggested that
      Internet harassment is a significant public health issue, with aggressors facing
      multiple psychosocial challenges including poor parent-child relationships,
      substance use, and delinquency. Comparisons to traditional bullies were made,
      with similarities and differences noted.

PMID- 15159092
TI  - Practising homelessness: a typology approach to young people's daily routines.
AB  - In a study exploring the relationship between typology and risk, we investigated
      the daily routines of a heterogeneous sample of young men and women from two
      sites who had been homeless for varying periods (N = 1289). Cluster analysis
      yielded four groups-'Partnered', 'Socially engaged', 'Service connected-harm
      avoidant', and 'Transgressive'-based on where and with whom they congregated and
      slept during the day and night and how they spent most of their time. Although
      the patterns of responses differed between the groups, there was overlap in the
      extent of engagement in specific activities, including risk practices.
      Interpretation of the impact of homeless young people's engagement in risk
      practices needs to take account of the interaction between their harmful and non
      harmful practices.

PMID- 15159094
TI  - Brief report: Initial psychometric properties of the everyday discrimination
      scale in black adolescents.
AB  - This study explored select psychometric properties of the Everyday Discrimination
      Scale in 120 Black adolescents (65 males and 55 females). Youth completed the
      Everyday Discrimination Scale and the Child Behaviour Checklist-Youth Self-Report
      Form. A t-test analysis revealed that Everyday Discrimination Scale scores were
      not significantly different for males and females (p > 0.18). The alpha
      reliability coefficient was 0.87, with item-total correlations that ranged from
      0.50 to 0.70 (mean=0.61). The split-half reliability was 0.83 (p < 0.0001). A
      principal component analysis yielded one factor, which accounted for
      approximately 49% of the standardized variance. Correlation analyses indicated
      that the Everyday Discrimination Scale score was significantly related to
      internalizing and externalizing symptoms (ps < 0.0002).

PMID- 15159093
TI  - The relationship of peer victimization to social anxiety and loneliness in
      adolescent females.
AB  - This study examined the relationship of overt and relational victimization to
      social anxiety, loneliness, and prosocial behaviours in a sample of female
      adolescents. The Social Experience Questionnaire, Social Anxiety Scale for
      Adolescents, and Asher Loneliness Scale were administered to 561 girls in the
      ninth, tenth, and eleventh grades of an urban parochial high school. Consistent
      with prior work, overt and relational victimization were positively associated
      with fear of negative evaluation, social avoidance of general and new situations,
      and loneliness. In addition, prosocial behaviours from peers moderated the
      effects of relational victimization on loneliness. Implications of these findings
      for the role of peer victimization and prosocial behaviours in female
      relationships are discussed.

PMID- 15159095
TI  - Brief report: Social and neighbourhood correlates of adolescent drunkenness: a
      pilot study in Cape Town, South Africa.
AB  - AIM: To identify social and neighbourhood correlates of drunkenness among
      adolescents. DESIGN: A cross-sectional, community study. PARTICIPANTS: A multi
      stage cluster sampling strategy was used to select 90 adolescents aged 11-17
      years from nine distinct communities in Cape Town, South Africa. The sample was
      stratified by race, income, and gender. Randomly selected adolescents from each
      household were interviewed by trained interviewers. INSTRUMENT: A questionnaire
      that included questions on substance use behaviour, peers, neighbourhood factors
      and recreational activities. RESULTS: A third of the sample indicated having been
      drunk at least once in their lifetime. Older adolescents and adolescents whose
      friends drink were significantly more likely to have been drunk. The risk of
      having been drunk was also associated with being white and with being exposed to
      public drunkenness on a daily or at least weekly basis. Gender was not associated
      with reporting of lifetime drunkenness. Attendance at religious services (at
      least weekly) was found to be a significant protective factor against
      drunkenness. CONCLUSION: The study highlights a number of environmental factors
      that should be considered in tackling adolescent drunkenness.

PMID- 15159096
TI  - Genetic parameters of libido in Brazilian Nellore bulls.
AB  - Genetic, environmental and phenotypic correlations between libido, testicular
      measurements, body weight and semen traits were estimated by multiple-trait
      restricted maximum likelihood (MTDFREML) under animal models. Reproductive
      records, collected from 1992 to 1997, of 288 Nellore bulls were used. Estimates
      of heritability for libido unadjusted, adjusted for scrotal circumference and
      adjusted for body weight, were 0.34 +/- 0.10, 0.31 +/- 0.10, and 0.19 +/- 0.11,
      respectively. Genetic correlations between libido and body weight, scrotal
      circumference, testis length, testis width, testis volume and testis consistency
      were, respectively, 0.69, -0.43, -0.31, -0.16, 0.10, 0.87, and between libido and
      semen volume, sperm motility, vigor, gross motility, major, minor and total
      defects were, respectively, 0.71, 0.51, 0.12, 0.16, 0.31, 0.26 and 0.43. Results
      suggested that selection for libido would be effective and that it would lead to
      desirable correlated response for scrotal circumference, physical and
      morphological semen traits and undesirable correlated response in body weight.

PMID- 15159097
TI  - Endometrial cytology and ultrasonography for the detection of subclinical
      endometritis in postpartum dairy cows.
AB  - The objectives of the study were to validate the use of endometrial cytology (EC)
      and ultrasonography (US) to diagnose subclinical endometritis in clinically
      normal postpartum dairy cows, and to measure the impact of subclinical
      endometritis on reproductive performance. Holstein cows from two dairy farms were
      examined at Visit 1 (V1) at 20-33 days in milk (DIM), and clinically normal cows
      (n = 228), based on the absence of abnormal discharge on external inspection and
      vaginoscopy, were selected. The reproductive tract of selected cows was evaluated
      by transrectal palpation, US and EC. All cows in the study were re-examined at
      Visit 2 (V2) at 34-47 DIM (2 weeks after V1) and were subsequently followed for a
      minimum of 8 months (until pregnant or culled). Survival analysis was used to
      derive a case definition of subclinical endometritis, based on factors associated
      with decreased relative pregnancy rate. Positive EC at V1 (>18% polymorphonuclear
      leukocytes; PMN) or fluid in uterus at V1 (FIU1) were associated with a
      significant reduction in the relative pregnancy rate and identified cows with
      subclinical endometritis. Similarly, a positive EC (>10% PMN) at V2 or fluid in
      the uterus at V2 (FIU2), identified cows with subclinical endometritis. Cows with
      subclinical endometritis at V1 and at V2 had a relative pregnancy rate of 41 and
      51% (hazard ratio for pregnancy of 0.59 and 0.49), respectively, compared to cows
      without subclinical endometritis. Given EC or US findings, no diagnostic criteria
      based on transrectal palpation of the uterus had predictive value for risk of
      pregnancy. In conclusion, subclinical endometritis, diagnosed by EC or US, was
      associated with reduced relative pregnancy rate.

PMID- 15159098
TI  - Preliminary study on the cryopreservation of tropical bagrid catfish (Mystus
      nemurus) spermatozoa; the effect of extender and cryoprotectant on the motility
      after short-term storage.
AB  - The effects of different extenders, and cryoprotectants on the motility of
      tropical bagrid catfish (Mystus nemurus) spermatozoa were evaluated after short
      term storage. Three extenders, physiological saline, Ringer or saline at three
      levels of sperm to extender dilutions (1:20, 1:30, or 1:40) and four
      cryoprotectants (DMSO, ethanol, glycerol or methanol) at three concentrations (5,
      10, or 15%) were examined in two separate experiments. In the first experiment,
      milt was suspended in the respective extender at the three milt to extender
      dilution ratios in two sets of tubes. Extended milt in the first set of tubes was
      stored at -4 degrees C, and motility assessed after 24h, while the second set was
      kept at 23 degrees C and sperm motility was assessed immediately and at 30-min
      intervals thereafter. Ringer retained sperm motility better than the other
      extenders at all dilution levels at temperatures of 23 and -4 degrees C
      respectively. At 23 degrees C, the sperm motility was almost completely lost
      after 150 min except for those in Ringer at 1:20 dilution level which still had a
      motility of 18% (compared to those kept at -4 degrees C for 24, which had
      motility from 39 to 71%, regardless of extender). In the second experiment,
      various cryoprotectants were added to solutions of milt (that was diluted in
      Ringer at 1:20 ratio and cryopreserved in liquid nitrogen for 15 days). Sperm
      cryopreserved in 10% methanol had the highest motility (58%) compared with those
      in the other cryoprotectants at all concentrations.

PMID- 15159099
TI  - Sexing in vitro produced bovine embryos, at different stages of development,
      using rat H-Y antiserum.
AB  - The male-specific H-Y antigen is present on mammalian cell membranes and has been
      identified by various methods, including antiserum cytotoxicity. The objective of
      the present study was to determine the sex of in vitro produced (IVP) bovine
      embryos, at varying stages of development, by culturing in the presence of rat
      monoclonal H-Y antibodies. Embryos derived from IVM/IVF were classified according
      to the interval after IVF (48, 96 or 120 h) as Category 1, 2 or 3 if they had 4
      to 8, <32, and >32 cells, respectively. Embryos of each category were cultured
      for 24h in TCM-199 supplemented with bovine oviductal epithelial cells, fetal
      calf serum (FCS), and antibiotics (Control group), to which the following had
      been added: guinea pig serum (GPS; C' group); H-Y antiserum (HY group); or GPS
      and H-Y antiserum (C' + HY group). After culture, embryos were designated as
      "affected" when development was arrested or one or more blastomeres was
      degenerate; embryos lacking these changes were designated "unaffected." The sex
      of each embryo was subsequently determined by chromosome analysis. After 48h of
      IVF (Category 1), within each of the four treatments, the proportion of
      unaffected embryos was higher than the proportion of unaffected embryos (81%
      versus 19%, P < 0.05). Similarly, the Control, C' and HY groups of Categories 2
      and 3 embryos had different proportions of unaffected versus affected embryos
      (75% versus 25%, P < 0.05). In all these groups, the male:female ratio did not
      significantly differ from 1:1. In contrast, in the C' + HY group of Categories 2
      and 3 embryos, the ratio of unaffected versus affected embryos was 41% versus 59%
      (P < 0.05) and the male:female ratio differed (P < 0.05) from the expected 1:1
      ratio (approximately 0.3:1 and 4.5:1 for unaffected versus affected,
      respectively). In conclusion, when bovine embryos were cultured in the presence
      of rat monoclonal H-Y antibodies and compliment, alterations occurred in embryos
      that were beyond the 8-cell stage; we inferred that the antibodies cross-reacted
      with H-Y antigens.

PMID- 15159100
TI  - Different strains of noncytopathic bovine viral diarrhea virus (BVDV) vary in
      their affinity for in vivo-derived bovine embryos.
AB  - Washing procedures (without trypsin treatment) recommended by the International
      Embryo Transfer Society (IETS) for use on in vivo-derived embryos effectively
      removed a cytopathic strain (NADL) of bovine viral diarrhea virus (BVDV) after
      artificial exposure. However, these washing procedures have not been evaluated
      using other isolates of BVDV, including representative non-cytopathic strains.
      Thus, the objective of this study was to evaluate the efficacy of the IETS
      procedures following artificial exposure of in vivo-derived bovine embryos to two
      different strains and biotypes of BVDV. One hundred and twenty-nine zona
      pellucida-intact (ZP-I) morulae and blastocysts (MB) and 56 non-fertile and
      degenerated (NFD) ova were collected 7 days following exposure to bulls from 32,
      BVDV-negative, superovulated cows. After collection, all MB and NFD ova were
      washed according to IETS standards. Subsequently, half of the MB and NFD ova were
      exposed for 1h to approximately 10(6)-cell culture infective doses (50% endpoint)
      per milliliter of viral strain SD-1, and the other half were exposed to the same
      concentration of CD-87. After exposure, groups of > or =3 and < or = 10 MB or NFD
      ova were washed using methods that met or exceeded IETS standards. Then, the
      washed groups were sonicated, and sonicate fluids were assayed for presence of
      virus using virus isolation and a reverse transcription nested polymerase chain
      reaction. No virus was detected in any group of MB or NFD ova that had been
      exposed to the CD-87 isolate. However, virus was detected in association with 50%
      of the groups of MB and 33% of the groups of NFD ova that had been exposed to the
      SD-1 isolate. Therefore, standard embryo-washing procedures recommended by the
      IETS are more effective for removal of some isolates of BVDV than for others. It
      remains to be determined if the quantity of a high-affinity isolate of BVDV
      associated with individual washed embryos would infect recipients via the
      intrauterine route. Further, it should be determined if an alternative embryo
      processing procedure, washing and trypsin treatment, would be more effective for
      removal of high-affinity isolates.

PMID- 15159101
TI  - Deslorelin on Day 8 or 12 postovulation does not luteinize follicles during an
      artificially maintained diestrous phase in the mare.
AB  - Practical estrus synchronization schemes are needed for mares. The Ovsynch
      synchronization protocol for cattle involves the administration of gonadotropin
      releasing hormone (GnRH) to induce ovulation or luteinization of dominant
      follicles during the luteal phase and prostaglandin 7 days later to cause
      regression of any luteal tissue and development of a preovulatory follicle. An
      Ovsynch-type synchronization program potentially could be developed for horses if
      luteinization or ovulation of diestrous follicles occurred in response to GnRH
      treatment. The objective of this study was to determine if administration of the
      GnRH agonist, deslorelin acetate, on Day 8 or 12 postovulation would induce
      luteinization or ovulation of diestrous follicles in the mare. The model used was
      cycling mares maintained in an artificial luteal phase by administration of a
      synthetic progestin following prostaglandin-induced luteal regression. On the day
      of ovulation, 21 light horse mares were randomly assigned to one of three groups:
      (1) no GnRH, altrenogest from Days 5 to 15 postovulation with prostaglandin on
      Day 15; (2) GnRH on Day 8, altrenogest from Days 5 to 15 with prostaglandin given
      on Day 6 to induce luteolysis of the primary corpus luteum, an implant containing
      2.1mg of deslorelin acetate inserted on Day 8 and removed on Day 10, with a
      second prostaglandin treatment on Day 15; (3) GnRH on Day 12, altrenogest from
      Days 9 to 19, prostaglandin on Day 10, a deslorelin acetate implant injected on
      Day 12 (subsequently removed on Day 14), and a second dose of prostaglandin
      administered on Day 19. Follicular development was monitored every other day from
      Day 5 until a 30-mm sized follicle was observed, and then daily to detection of
      ovulation. Serum progesterone concentrations were determined daily for 12
      consecutive days. Progesterone concentrations in Group 1 remained elevated until
      approximately Day 12 postovulation. Prostaglandin administration on Day 15
      resulted in complete luteolysis in all seven mares. In Group 2, progesterone
      concentrations in six of seven mares declined to baseline after prostaglandin
      treatment. No increase in serum progesterone was noted in any of the six mares
      that were given GnRH on Day 8, including three mares that had diestrous follicles
      > or =30mm in diameter at the time of treatment. Similarly, progesterone
      concentrations in six of seven mares in Group 3 declined to baseline after
      prostaglandin and there was no increase in progesterone after administration of
      GnRH on Day 12. No ultrasound evidence of luteinization or ovulation of diestrous
      follicles were noted after GnRH administration in any mares of Group 2 or 3. In
      conclusion, administration of the GnRH agonist deslorelin acetate to mares failed
      to induce luteinization or ovulation of diestrous follicles. Consequently, the
      Ovsynch program (as used in cattle) has little efficacy for synchronization of
      estrus in mares.

PMID- 15159102
TI  - Morphological and ultrastructural analysis of sheep primordial follicles
      preserved in 0.9% saline solution and TCM 199.
AB  - The objective was to determine the morphological and ultrastructural features of
      sheep primordial follicles preserved in either 0.9% saline solution or TCM 199 at
      different temperatures. Soon after death, the ovarian pair of each ewe (n = 5)
      was divided into 25 fragments. One fragment was immediately fixed for
      morphological evaluation (control). The other 24 fragments were randomly
      distributed in tubes containing 2 ml of 0.9% saline solution or TCM 199 and
      maintained at 4, 20 or 39 degrees C for 2, 4, 12, or 24h. Based on histological
      assessment, storage of ovarian fragments in 0.9% saline solution at 20 degrees C
      for up to 24h and in both solutions at 39 degrees C for 4, 12 or 24h increased (P
      < 0.01) the percentage of degenerate primordial follicles compared with controls.
      In contrast, preservation at 4 degrees C in both solutions, kept the percentage
      of morphologically normal primordial follicles similar to control values.
      Although histological integrity of primordial follicles was maintained in
      fragments stored at 20 degrees C for up to 24h in TCM 199, these results were not
      confirmed by ultrastructural analysis. Based on transmission electron microscopy,
      only primordial follicles stored at 4 degrees C for up to 24h, at 20 degrees C
      for up to 12h and at 39 degrees C for up to 2h in both solutions were
      ultrastructurally normal. In conclusion, sheep primordial follicles were
      successfully preserved at 4 degrees C for up to 24h, at 20 degrees C for up to
      12h and at 39 degrees C for 2h in 0.9% saline solution or TCM 199.

PMID- 15159103
TI  - Efficacy, safety and reversibility of bisdiamine as a male contraceptive in cats.
AB  - Bisdiamines have potential as a male contraceptive due to their ability to arrest
      spermatogenesis. The bisdiamine WIN 18,446, has proven safe and effective in grey
      wolves, domestic dogs, rats, and humans, but the unique drug metabolism of cats
      make extrapolation to felids inappropriate. This study used domestic cats to test
      the efficacy and safety of bisdiamines in felids. Five domestic cats were given
      150mg/kg WIN 18,446, mixed in food daily from Day 0 to Day 76, and were monitored
      until Day 152. Cats were observed daily and weighed weekly. Physical exam,
      hematology, clinical chemistry and urinalysis were conducted on Days 0, 7, 14,
      28, 76, and 152 of the trial. Serum testosterone concentrations were measured on
      Days 0, 75, and 152. Unilateral orchectomies were performed on Days 76 and 152,
      and testes evaluated by histopathology. Spermatogenic arrest occurred in all cats
      during the treatment period, but normal spermatogenesis was restored by Day 152.
      Serum testosterone concentrations were lower on Day 76 (2.62 +/- 2.5 ng/ml; P <
      0.01) than Day 0 (7.3 +/- 1.0 ng/ml), but returned to pre-treatment
      concentrations in four of five cats by Day 152 (6.16 +/- 2.1 ng/ml; P >0.05).
      Clinical pathology parameters remained within reference ranges during the
      treatment period; however, urine calcium oxalate crystals were noted only during
      treatment in three cats. Bisdiamine (WIN 18,446) was a safe and effective
      contraceptive for male cats, but testosterone concentrations decreased during
      treatment.

PMID- 15159104
TI  - Influence of season of birth on growth and reproductive development of Brahman
      bulls.
AB  - Seasonal effects on reproduction are more dramatic in Bos indicus than Bos taurus
      cattle. This experiment evaluated reproductive development of fall- (n=7) versus
      spring- (n = 10) born Brahman bulls to determine if season of birth affects
      reproductive development. Measurements of growth and reproductive development
      began after weaning and continued at bi-weekly intervals until each bull reached
      sexual maturity. Different stages of sexual development were classified according
      to characteristics of the ejaculate and included first sperm in the ejaculate,
      puberty (> 50 x 10(6) sperm/ejaculate), and sexual maturity (two ejaculates with
      > 500 = 10(6) sperm/ejaculate). Average daily increases in all measured traits
      were similar in fall- and spring-born bulls and there were no differences in age,
      body weight, scrotal circumference, or paired testis volume between groups at
      first sperm or puberty. However, fall-born bulls were older (P < 0.05) than
      spring-born bulls at sexual maturity (553 days versus 481 days, respectively) as
      the interval between puberty and sexual maturity was longer (P < 0.05) in fall-
      than in spring-born bulls (82 days versus 54 days, respectively). The prolonged
      interval between puberty and sexual maturity in fall-born calves coincided with a
      short photoperiod (winter) whereas the short interval between puberty and sexual
      maturity in spring-born calves coincided with a long photoperiod (summer). In
      conclusion, season of birth affected sexual development; photoperiod might be
      involved in regulating testicular function immediately after puberty in Brahman
      bulls.

PMID- 15159105
TI  - Changes in EGF concentrations during estrous cycle in bovine endometrium and
      their alterations in repeat breeder cows.
AB  - The objective of the present study was to determine if abnormalities in the
      cyclic changes of endometrial EGF concentrations can be a diagnostic tool for
      repeat breeder cows. First, the profile of EGF concentrations during the estrous
      cycle was determined using endometrial tissues obtained from 31 Holstein cows
      after slaughter. Cyclic cows had two peaks of EGF concentrations. Then,
      endometrial tissues were obtained from 12 control and 20 repeat breeder cows by
      biopsy on Days 3, 7, and 14 of the same estrous cycle. Endometrial EGF
      concentrations in biopsied samples of the controls were similar to those found in
      slaughterhouse materials; they were high on Days 3 and 14 (9.2 and 10.4 ng/g
      tissue, respectively) and low on Day 7 (3.8 ng/g tissue). Concentrations of EGF
      in repeat breeder cows had a different profile; they were similar on Days 3, 7,
      and 14 (4.4, 3.4, and 4.0 ng/g tissue, respectively). In conclusion, changes in
      endometrial EGF concentrations were altered in repeat breeders; these alterations
      may be a potential diagnostic marker for repeat breeder cows.

PMID- 15159106
TI  - Pre-weaning performance and health of pigs born to cloned (fetal cell derived)
      swine versus non-cloned swine.
AB  - The objective of this study was to compare the pre-weaning performance of pigs
      derived from cloned versus non-cloned parents. Five cloned gilts and one cloned
      boar were used to produce five litters of pigs. One of five cloned females and
      the cloned boar were derived from two genetically unmanipulated fetal fibroblast
      cell lines. The remaining female clones were derived from a fetal fibroblast cell
      line in which random insertion of a alpha-1,3-galactosyltransferase gene
      targeting construct had occurred. Fetal cell lines had similar genetic
      backgrounds and were derived from three different fetuses in three different
      litters. Five litters of pigs were also generated from matings between two non
      cloned boars and five non-cloned gilts. The mean gestation length, mean litter
      size, mean birth and weaning weights for male and female pigs were similar for
      litters derived from cloned parents versus non-cloned parents. The proportions of
      pigs born live and pigs that survived to weaning were also similar for pigs born
      to cloned as compared to non-cloned parents. In summary, matings between cloned
      swine derived from fetal fibroblast cell lines yielded litters of pigs that were
      similar in the number born, piglet birth weight and perinatal and pre-weaning
      mortality to litters produced by non-cloned swine.

PMID- 15159107
TI  - Prostaglandin F2alpha-induced estrus in ewes exhibiting estrous cycles of
      different duration.
AB  - Effects of prostaglandin F(2alpha) (PGF(2alpha)), administered during the mid
      luteal phase of the estrous cycle, were examined in ewes exhibiting estrous
      cycles classified as short (< or =16.5 days, short-cycle ewes, n = 10) or long (>
      or =18 days, long-cycle ewes, n = 9) based on the durations of two estrous cycles
      (cycles -2 and -1) before treatment. The ewes received (i.m.) 20mg of PGF(2alpha)
      on day 10 of the third estrous cycle (cycle 0) followed, 36 h later, by 25 microg
      of gonadotropin releasing hormone (GnRH) to time the events of ovulation.
      Duration of subsequent estrous cycles +1 and +2 were recorded, and then the ewes
      were treated with the same combination of PGF(2alpha) and GnRH beginning on day
      10 of estrous cycle +3. Ovaries were recovered 6h after GnRH administration to
      assess development of pre-ovulatory follicles. The proportion of ewes that
      exhibited estrus after PGF(2alpha) and GnRH treatment on cycle 0 was not
      different (P > 0.05) between short- and long-cycle ewes. Onset of estrus occurred
      sooner (P < 0.05) after PGF(2alpha) injection in short-cycle ewes than in long
      cycle ewes (1.9 +/- 0.1 days and 2.3 +/- 0.1 days, duration of cycle 0 was 11.9
      and 12.3 days, respectively). Duration of estrous cycle +1 was 1.2 days longer (P
      < 0.01) than cycle -1 in short-cycle ewes. However, duration of estrous cycle +1
      did not change (P > 0.05) after PGF(2alpha) and GnRH administration in ewes
      having long cycles. Pre-ovulatory follicles did not differ (P > 0.05) in numbers,
      diameter, layers of granulosa cells nor concentrations of progesterone and
      estradiol-17beta in follicular fluid between short- and long-cycle ewes after
      PGF(2alpha) and GnRH treatment. In conclusion, ewes having short or long estrous
      cycles responded differently to PGF(2alpha) and GnRH treatment with respect to
      the interval to onset of estrus and duration of the subsequent estrous cycle.

PMID- 15159108
TI  - Collection and evaluation of semen from captive howler monkeys (Alouatta caraya).
AB  - Semen samples (n=58) were collected by electroejaculation from nine adult male
      howler monkeys (Alouatta caraya) between November 2000 and August 2001 at the
      National Primates Center, Ananindeua, Brazil. The ejaculates were free of
      coagulum. Mean (+/-S.D.) values were: volume, 0.09 +/- 0.05 ml; pH, 8.1 +/- 0.5;
      concentration 649.5 +/- 926.7 x 10(6) sperm/ml; progressive motility, 75.8 +/-
      18.1%; forward progressive sperm motility (scale, 0-5), 3.5 +/- 1.0; live
      spermatozoa, 68.3 +/- 15.0%; primary defects, 9.6 +/- 4.5%; and secondary
      defects, 11.8 +/- 4.6%. There were high correlations between motility and live
      sperm (r = 0.91, P < 0.01), motility and forward progressive sperm motility (r =
      0.84, P < 0.01) and between forward progressive sperm motility and live sperm (r
      = 0.78, P < 0.01). There were no alterations observed during clinical
      examinations and hematological analysis performed before and after semen
      collection. Therefore, the method was considered safe and efficient. It can be
      used for the evaluation of the breeding potential of male howler monkeys in
      captivity and for the establishment of new assisted reproductive technology (ART)
      for threatened species of neotropical primates.

PMID- 15159109
TI  - Semen characteristics, cryopreservation, and successful artificial insemination
      in the Blue rock pigeon (Columba livia).
AB  - The present study was undertaken in the Blue rock pigeon (Columba livia) to
      evaluate the annual semen characteristics, to identify a suitable extender for
      semen short-term storage, to determine a protocol for cryopreservation of semen
      and finally to check whether intracloacal insemination would lead to the birth of
      a chick. Semen characteristics such as semen volume, sperm concentration, sperm
      motility, and percentage of normal spermatozoa were maximum during the monsoon
      season. TALP was observed to be the most suitable semen extender and the sperm
      survived best at 37 degrees C at a dilution of 1:100 in TALP. Further,
      cryopreservation studies on pigeon semen indicated that 8% DMSO with or without
      egg yolk (20%) proved to be a better cryoprotectant compared to glycerol and
      polyethylene glycol. In addition, the slow freezing protocol was better than the
      fast-freezing protocol and about 40% of the cryopreserved spermatozoa were motile
      following thawing. Computer-aided semen analysis indicated that pigeon
      spermatozoa were extremely active immediately after dilution in TALP and
      exhibited linear trajectories persisting up to 9h. But, with time there was a
      time-dependent decrease in the velocity parameters (VAP, VSL, and VCL).
      Cryopreserved spermatozoa following thawing also exhibited linear trajectories
      but had reduced velocity as evident from the significant decrease in VAP, VSL,
      and VCL. Further, artificial inseminations using fresh semen resulted in 45%
      fertilization and birth of a live chick.

PMID- 15159110
TI  - Development of in vivo derived diploid and tetraploid pig embryos in a modified
      medium NCSU 37.
AB  - The aim of this study was to assess development of diploid and tetraploid in vivo
      derived pig embryos cultured in a modified medium NCSU 37 in an atmosphere with
      reduced concentration of oxygen. The tetraploid embryos were produced by
      electrofusion of two-cell embryos that had been cultured in vitro from the one
      cell stage before fusion (cultured two-cell embryos) or by fusion of freshly
      recovered two-cell embryos. Development to blastocyst stage of tetraploid
      embryos, generated from the cultured two-cell embryos was significantly inferior
      to the development of control one-cell embryos (29.1 +/- 9.7% versus 66.8 +/-
      9.7%; P < 0.05). However, development of tetraploid embryos produced from the
      freshly recovered two-cell embryos and control two-cell embryos was very similar
      (89.9 +/- 6.1% versus 81.3 +/- 3.4%). Detection of chromosomes 1 and 10 by in
      situ hybridization showed that more than 85% of the cultured control embryos were
      diploid while 15% of the embryos were mosaic. Among the fused embryos 50% were
      tetraploid, 29% mosaic and 21% diploid. These data indicate that the modified
      medium NCSU 37 provides optimum environment for pre-implantation development of
      pig diploid and tetraploid embryos.

PMID- 15159111
TI  - Improvement in spermatogenic function after subcutaneous implantation of a
      capsule containing an aromatase inhibitor in four oligozoospermic dogs and one
      azoospermic dog with high plasma estradiol-17beta concentrations.
AB  - A capsule containing an aromatase inhibitor (4-androsten-4-ol-3,17-dione) was
      subcutaneously implanted in four oligozoospermic beagle dogs and one azoospermic
      beagle dog with high plasma estradiol-17beta (E2) concentrations (15-19 pg/ml)
      and low plasma testosterone (T) concentrations (0.6-0.8 ng/ml) for 8 weeks and
      the effect of the aromatase inhibitor on spermatogenic dysfunction was assessed.
      Plasma E2 and T concentrations and semen quality were examined at 1 week
      intervals from 3 weeks before to 12 weeks after the start of treatment.
      Testicular biopsies were done twice (capsule implantation and removal). Plasma E2
      concentrations of all dogs decreased (9-14 pg/ml) and plasma T concentrations
      increased (2.0-2.6 ng/ml) from 3 weeks after capsule implantation to capsule
      removal. The mean number of spermatozoa ejaculated by all four oligozoospermic
      dogs between 4 and 9 weeks after implantation was higher (127 x 10(6) to 205 x
      10(6)) than before implantation (20 x 10(6) to 38 x 10(6)) (P < 0.05 and 0.01).
      Very low numbers (2 x 10(4) to 4 x 10(4)) of immotile spermatozoa were observed
      between 7 and 8 weeks after implantation in the semen collected from the dog with
      azoospermia. Before implantation, a few spermatozoa were seen in only one-fifth
      of the seminiferous tubules in this dog; 8 weeks after implantation, the mean
      diameter and mean number of round spermatids in the seminiferous tubules in all
      five dogs were higher than before implantation (P < 0.05). Implantation of the
      capsule containing the aromatase inhibitor in infertile dogs with abnormally high
      plasma E2 concentrations improved their spermatogenic function, concurrent with
      decreased plasma E2 and increased plasma T.

PMID- 15159113
TI  - Rate of abnormalities in lambs from in vitro produced embryos transferred on Day
      2 compared with Day 6 postfertilization.
AB  - The effect of transferring ovine IVP embryos on Day 2 versus Day 6
      postinsemination was investigated. Oocytes were collected from 35 cull ewes and
      cultured separately for each donor. Embryos were exposed to serum in the
      maturation and fertilization media, and then cultured in a serum-free SOF system
      under serum-conditioned silicone oil. Cleaved Day 2 postfertilization embryos
      were randomly allocated for immediate transfer versus Day 6 transfer. Parturition
      was induced (with 15 mg dexamethasone) between Days 141 and 143 of pregnancy;
      those failing to initiate parturition by Day 146 had a Caesarean section.
      Stillborn lambs and those dying within several days of birth were necropsied.
      Lambs were weighed at birth; lambs (n = 132) derived from the same flock (from
      natural breeding or AI) were used as a control. An estimate of the 99th
      percentile of the normal population was used as the point above which lambs from
      three litter-size categories were classified as abnormally large (analysis was
      repeated for 95% confidence and median estimates of this value). Thirty-eight
      lambs were born from early transfer, 45 from late transfer and 12 from unobserved
      lambings (parentage could not be determined). Lambs from early transfer were
      heavier at birth (P = 6.0 x 10 (-11)). The early treatment group had fewer lambs
      produced per embryo transferred (P = 0.0002), fewer live lambs per embryo
      transferred (P = 0.00009) and fewer normal lambs per embryo transferred (P=
      0.0002). There was an effect of donor on the number of dead lambs per embryo
      transferred (P = 0.017). The number of dystocias per transfer was not
      significantly different for early versus late transfer groups. However, the
      probabilities of survival for cleaved embryos were 27.3% and 13.1% in the early
      and late transfer treatment, respectively. There were more lambs produced per
      cleaved embryo with early transfer (P = 0.004) and there was an effect of donor
      within ram and replicate (P = 0.04) on the number of lambs produced. The odds
      ratio for early/late treatment was 2.449 with a confidence interval of 1.368
      4.382. Day 2 transfer of cleaved embryos did not prevent the production of
      oversized or abnormal offspring; however, there was an increased chance of a
      cleaved embryo producing a lamb when transferred on Day 2 rather than Day 6
      postfertilization.

PMID- 15159112
TI  - Initial studies on sperm cryopreservation of a live-bearing fish, the green
      swordtail Xiphophorus helleri.
AB  - Swordtails and platyfish of the genus Xiphophorus are valuable models for
      biomedical research and are also commercially raised as ornamental fish valued by
      aquarists. While research use and commercial interest increases yearly in these
      fish, cryopreservation of sperm is unexplored in this genus. Xiphophorus are live
      bearing fishes characterized by small body sizes, limited sperm volumes, and
      internal fertilization, an atypical reproductive mode for fish. These attributes
      make research involving cryopreservation of Xiphophorus germplasm challenging. To
      explore methods for sperm cryopreservation, this study evaluated the effect of
      different loading volumes of sperm suspension in 0.25-ml French straws, different
      dilution ratios of sperm to extender, an osmolality range of extender without
      cryoprotectant and with dimethyl sulfoxide (DMSO) as cryoprotectant, and short
      term storage at room temperature and 4 degrees C after thawing. No significant
      difference in sperm motility due to straw loading volume was observed after
      thawing. Sperm motility was observed to decrease with increasing dilution. The
      osmolality of Hanks' balanced salt solution (HBSS) without cryoprotectant in
      which the highest sperm motility (67%) was observed was 320 +/- 3 mOsm/kg, which
      was also the osmolality of X. helleri blood plasma. When cryopreserved with 10%
      DMSO, however, the highest motilities within 10 min after thawing were observed
      with HBSS in the range of 240-300 mOsm/kg. Sperm suspended in HBSS at 320 mOsm/kg
      with a dilution factor of 100 maintained motility for 24h at room temperature,
      but persisted for 10 days when stored at 4 degrees C. These results provided the
      first evidence that cryopreservation may be applied to conservation of genetic
      resources in live-bearing fishes.

PMID- 15159114
TI  - Effects of PDC-109 on bovine sperm functional activity in presence or absence of
      heparin.
AB  - PDC-109, a heparin-binding protein (from the seminal vesicles) that binds to
      sperm surface phospholipids at ejaculation, may modulate several aspects of sperm
      activity. The objectives of the present study were to determine: (1) in the
      presence or absence of heparin, the effects of exogenous PDC-109 on sperm
      motility (Makler chamber), viability (Hoechst 33258) and membrane functional
      integrity (hypoosmotic swelling test) of bovine spermatozoa; (2) the role of PDC
      109 as a capacitation-inducing factor; and (3) its ability to induce the acrosome
      reaction (fluorescein staining). After 4-h capacitation in the presence of
      heparin, the addition of PDC-109 (0.5, 1.5 or 3.0mg/ml) significantly decreased
      the percentages of motile, progressive, and viable cells; these effects were also
      detected in the absence of heparin. However, PDC-109 elicited a twofold increase
      (from 14 to 28%) in the proportion of acrosome-reacted spermatozoa, but only in
      the presence of heparin. Progesterone (10 microM) or angiotensin II (100 or 1000
      nM) stimulated the acrosome reaction after capacitation in the presence of PDC
      109 without heparin (from 10 to 17, 23 and 22%, respectively). In conclusion, PDC
      109 appears to modulate sperm functional activity, with some effects manifest in
      the absence of heparin.

PMID- 15159115
TI  - Luteal function and conception in lactating cows and some factors influencing
      luteal function after first insemination.
AB  - The objective of this study was to investigate the types and incidence of luteal
      sub-function in lactating cows after artificial insemination (AI) and their
      relationship with pregnancy, and to clarify the relationship between luteal
      function and parity, body condition score (BCS), milk yield, and dietary intake.
      In 19 cows, milk samples were collected daily from AI to confirmation of
      pregnancy. Milk progesterone concentrations were determined by EIA. Based on peak
      progesterone concentration and the day of onset of luteal phase, 15 of 30
      progesterone profiles (50%) were normal, with progesterone concentration reaching
      1.0 ng/ml within 5 days after insemination and > or =2.0 ng/ml thereafter. In
      addition, 6 (20%) were insufficient, (progesterone concentration remained < 2.0
      ng/ml), 5 (17%) were delayed (progesterone reached 1.0 ng/ml after 5 days), 2
      (7%) were both delayed and insufficient, one (3%) was short (progesterone >1.0
      ng/ml for only 7 days), and one (3%) remained basal. Cows with a normal profile
      had a higher (P < 0.05) pregnancy rate than those with an abnormal profile (87%
      versus 33%, respectively). The amount of progesterone secreted in milk after
      first AI, as indicated by progesterone area under curve (AUC), was negatively
      correlated with milk yield (r = -0.83, P < 0.01), dry matter intake (r = -0.81, P
      < 0.05), total digestible nutrients (r = -0.82, P< 0.05), and digestible crude
      protein (r = -0.79, P <0.05). Cows that produced more milk and consumed more dry
      matter had less progesterone during the luteal phase. In conclusion, abnormal
      luteal function was associated with reduced pregnancy rates and high milk
      production and increased dietary intake during breeding were associated with
      reduced progesterone concentrations.

PMID- 15159116
TI  - A simple ultrasound test to predict the superstimulatory response in cattle.
AB  - We tested the hypotheses that: (1) the superstimulatory response is related to
      the intrinsic number of follicles recruited into a follicular wave; and (2) the
      number of follicles recruited into a wave is correlated to the number of
      follicles recruited into the successive wave. A positive correlation will form
      the basis of a test for predicting the superstimulatory response. Cows (n = 141)
      were treated with estradiol and progesterone to synchronize follicular wave
      emergence (first synchronization) and ranked according to the number of follicles
      > or =2mm at wave emergence to select the upper and lower 10% of the herd.
      Follicular wave emergence was synchronized again in the high-end (n = 16) and low
      end (n = 20) groups (second synchronization), and cows were treated with FSH
      twice daily for 3 days. High-end cows had a greater number of follicles (P <
      0.001) than low-end cows at the time of wave emergence after both the first and
      second synchronizations in the 2-3 and 4-6mm categories. The numbers of 2-3 and 4
      6mm follicles at wave emergence after the first and second synchronizations were
      positively correlated (P < 0.001; r = 0.77 and 0.71, respectively). Endogenous
      FSH peak at the time of wave emergence was higher in the low-end group than in
      the high-end group. Superstimulatory treatment resulted in more than double the
      number of follicles (P < 0.003) in the 5-7mm and > or =8mm categories in the high
      end group than in the low-end group (16.8 +/- 2.2 versus 8.1 +/- 0.9 and 22.7 +/-
      4.1 versus 9.7 +/- 1.6, respectively). The number of follicles > or =5 and > or
      =8mm at the end of superstimulation was positively correlated (P < 0.001) with
      the total number of follicles > or =2mm at the time of wave emergence after both
      the first (r = 0.64 and 0.54, respectively) and second ( r = 0.65 and 0.5,
      respectively) synchronizations. Based on the results of this study, the
      superstimulatory response can be predicted by the number of follicles > or =2mm
      at wave emergence. For practical purposes, practitioners can expect the number of
      follicles > or =5mm after ovarian superstimulation to be approximately 71% of the
      number of follicles > or =2mm at the time of wave emergence. Results validated
      the proposed simple ultrasound-based test for predicting the superstimulatory
      response of individual cows.

PMID- 15159117
TI  - Regulatory roles of ubiquitin-proteasome pathway in pig oocyte meiotic maturation
      and fertilization.
AB  - The ubiquitin-proteasome pathway is involved in the degradation of proteins
      related to cell cycle progression including cyclins. The present study, using two
      specific proteasome inhibitors, for the first time investigated the roles of
      ubiquitin-proteasome in cell cycle progression during pig oocyte meiotic
      maturation and after fertilization. In contrast to its effect in rodent oocytes,
      proteasome inhibition strongly prevented germinal vesicle breakdown (GVBD). After
      GVBD, proteasome inhibition disrupted meiotic apparatus organization, cell cycle
      progression, and first polar body (PB1) extrusion. Sperm penetration into the
      oocytes was completely inhibited when proteasome inhibitors were added at the
      beginning of insemination. However, sperm chromatin decondensation and metaphase
      interphase transition were not affected when inhibitors were added once sperm
      penetrated. The results suggest that ubiquin-proteasome complex is one of the
      critical regulators of meiotic cell cycle, but proteasome inhibitors do not
      affect major fertilization events when added after sperm penetration into the
      oocytes in the pig.

PMID- 15159118
TI  - Ultrasonographic evaluation of uterine involution and postpartum follicular
      dynamics in French jennies (Equus asinus).
AB  - Uterine involution and follicular dynamics during postpartum period were studied
      ultrasonographically in French jennies. For the study of uterine involution in
      postpartum jennies (n = 6, Group S), sonographic measurements of different parts
      of the uterus and endometrium were made at three-day interval, starting from the
      day of foaling and continued up to 33 days postpartum. Uterine dimensions were
      also recorded in non-pregnant jennies (n = 3, Group C) throughout a cycle and
      compared with the dimensions of Group S jennies observed on the day of complete
      involution. Follicular dynamics of first and second postpartum ovulatory cycles
      were studied and compared with that of the single estrous cycle of Group C
      jennies. Jugular venous blood samples of Group S jennies were collected at weekly
      intervals for 49 days, commencing at the appearance of first preovulatory
      follicle, to support the sonographic findings. The average involution period was
      22.5 +/- 1.7 days. However, it was significantly delayed (P < 0.05) in jennies
      which came into first postpartum ovulatory heat within Day 9 than those who came
      later (25.0 +/- 1.0 versus 20.0 +/- 1.0). The endometrial layer was not
      discernible beyond Day 15 postpartum and thus was found to be unreliable index of
      uterine involution. The follicular growth rate (mm per day) and diameter (mm) of
      preovulatory follicle in postpartum jennies were similar to that in normal
      cycling jennies (P > 0.05). The first and second ovulations occurred at 14.6 +/-
      0.8 and 39.0 +/- 0.8 days postpartum in Group S jennies. All the corpora lutea,
      either echogenic or centrally non-echogenic were functionally similar and had
      similar life span (P > 0.05). In conclusion, the postpartum reproductive events
      related to uterine involution and ovarian cyclicity apparently resemble that of
      mares.

PMID- 15159119
TI  - Estradiol benzoate given 0 or 24 h after the end of a progestagen treatment in
      postpartum suckled beef cows.
AB  - The objective of Experiment 1 was to compare the effects of estradiol benzoate
      (EB) given 0 or 24h after the end of a progestagen treatment on ovulation and CL
      formation in anestrous cows. Twenty cows were treated with an intravaginal sponge
      containing 250 mg of medroxiprogesterone acetate (MPA). At sponge insertion, each
      cow received 3 mg EB and 10 mg MPA im. At device removal, cows received 0.7 mg EB
      either at that time (EB0) or 24h later (EB24). Ultrasound examinations and blood
      sampling to determine plasma progesterone concentrations were performed to detect
      ovulation and CL formation. Ovulation occurred in 77.8 and 81.8% cows in the EB0
      and EB24 groups, respectively. Diameter of the ovulatory follicle (EB0 = 10.9 +/-
      0.5mm; EB24 = 12.1 +/- 0.8 mm; P = 0.26) and the interval from sponge removal to
      ovulation (median = 3 days; P = 0.64) did not differ between treatments. Among
      the cows that ovulated (n = 16), short-lived CL were present in 2/7 and 2/9 cows
      in the EB0 and EB24 groups, respectively. Plasma progesterone concentrations and
      CL area did not differ between treatments (P > 0.05). In Experiment 2, cows were
      treated with the same protocol as in Experiment 1, but at sponge withdrawal all
      cows received 250 microg cloprostenol and timed artificial insemination (TAI) was
      performed 48 h after sponge removal. In Replicate 1 (n = 204 multiparous cows),
      pregnancy rates were 45.0 and 47.5% for EB0 and EB24, respectively (P > 0.05). In
      Replicate 2 (n = 69 primiparous cows) pregnancy rate did not differ between EB0
      and EB24 (51.4% versus 52.9%). In conclusion, EB given 0 or 24h after the end of
      a progestagen treatment had the same effect on ovulation rate, time to ovulation,
      diameter of the ovulatory follicle, incidence of short-lived CL, luteal tissue
      area, and plasma progesterone concentrations of normal lifespan CL, and pregnancy
      rate after TAI in suckled beef cows.

PMID- 15159120
TI  - Seasonal variation in testicular volume and sexual behavior of Chios and Serres
      rams.
AB  - The seasonality of testicular volume and sexual behavior in two Greek breeds of
      sheep, Chios and Serres, was studied using 10 mature rams of each breed. The rams
      were kept out of breeding during 2 consecutive years. Live weight was recorded at
      monthly intervals. Testicular volume was measured at 2-week intervals using an
      orchidometer. Sexual behavior was recorded at 4-week intervals by exposing rams
      to oestradiol-treated ovariectomized ewes. The total number of mounts and
      matings, and the reaction time to first mount and mating were recorded. Chios
      rams were heavier than Serres rams (87.4 +/- 2.0 kg versus 76.4 +/- 1.9 kg,
      respectively). All traits varied significantly with month but only testicular
      volume exhibited a clear seasonal trend in both breeds, with a maximum volume in
      July-August and a minimum in February-April. Number of mounts showed clear
      seasonal trend in the Chios breed, with maximum in November. Number of mounts was
      significantly correlated with length of daylight (-0.18 and -0.21 for Chios and
      Serres, respectively; P < 0.01) and relative humidity (0.14 and 0.17 for Chios
      and Serres, respectively; P < 0.05). Testicular volume was positively correlated
      with air temperature (0.28; P < 0.01) and relative humidity (-0.23; P < 0.01) in
      the Serres breed only. Results of this study suggest that the testicular volume
      and number of mounts exhibit seasonal variation in the Chios and Serres rams.

PMID- 15159121
TI  - Germ cell apoptosis in the testes of normal stallions.
AB  - Apoptosis in testicular germ cells has been demonstrated in many mammalian
      species. However, little is known about the stallion (Equus caballus) and rates
      of apoptosis during spermatogenesis. Morphological and biochemical features of
      apoptosis reported in other species were used to confirm that the TdT-mediated
      dUTP Nick end labeling (TUNEL) assay is an acceptable method for identification
      and quantification of apoptotic germ cells in histological tissue sections from
      stallion testis. Seminiferous tubules from eight stallions with normal testis
      size and semen quality were evaluated according to stage of seminiferous
      epithelium to determine the germ cell types and stages where apoptosis most
      commonly occurs. Spermatogonia and spermatocytes were the most common germ cell
      types labeled by the TUNEL assay. A low rate of round and elongated spermatids
      were labeled by the TUNEL assay. Mean numbers of TUNEL-positive germ cells per
      100 Sertoli cell nuclei were highest in stages IV (15.5 +/- 1.0) and V (13.5 +/-
      1.1) of the seminiferous epithelial cycle (P < 0.001). An intermediate level of
      apoptosis was detected in stage VI (P < 0.02). These stages (IV-VI) correspond to
      meiotic divisions of primary spermatocytes and mitotic proliferation of B1 and B2
      spermatogonia. Establishing basal levels of germ cell apoptosis is a critical
      step towards understanding fertility and the role of apoptosis in regulating germ
      cell numbers during spermatogenesis.

PMID- 15159122
TI  - Effect of undegradable protein supply on testicular size, spermiogram parameters
      and sexual behavior of mature Assaf rams.
AB  - Eighteen mature Assaf rams were used to study the effect of undegradable protein
      (UDP) supply on testicular size, sperm production and quality, testosterone
      secretion and reproductive behavior. Animals were allocated to three groups of
      six animals each and fed during 10 weeks with different diets which were designed
      to supply approximately 0.5MJ of metabolisable energy (ME)/kg LBW(0.75) and 9g of
      effective rumen degradable protein (ERDP)/MJ of fermentable ME to all animals and
      to induce differences in rumen UDP intake (0.97, 1.72 and 3.08g of UDP/kg
      LBW(0.75) for LP, MP and HP diets, respectively). Neither plasma testosterone
      concentration nor reproductive behavior parameters (number of services, number of
      mounts without ejaculation and reaction time to first mount) were affected (P >
      0.05) by protein intake. Nevertheless, there were significant (P < 0.05)
      differences between diets in both testicular size and sperm production. Scrotal
      circumference was lower in LP compared to MP and HP groups, no significant
      differences being observed between these latter two groups at any time. In
      relation to sperm production, the lowest and the highest values were always
      observed in LP and HP groups, respectively. MP group showed intermediate values,
      significantly different from those of LP and HP groups on Week 5 and only from
      those of LP group on Week 9. The present results provide a better understanding
      of the effect of protein nutrition and suggest that UDP should be supplied to
      Assaf rams during the mating season to improve their reproductive performance.

PMID- 15159123
TI  - Exogenous gamma-glutamyl cycle compounds supplemented to in vitro maturation
      medium influence in vitro fertilization, culture, and viability parameters of
      porcine oocytes and embryos.
AB  - High concentrations of intracellular glutathione (GSH) enhance in vitro
      production of porcine embryos. Objectives were: (1) to determine the effects of
      gamma-glutamyl cycle compound supplements to the IVM medium on IVF and IVC; and
      (2) to evaluate embryo viability. Porcine oocytes were matured in NCSU 23 medium
      supplemented with either l-cysteine (3.3 mM), l-cysteamine (150 P < 0.05microM),
      l-cysteine and l-cystemaine, l-glycine (1, 2.5, or 5 mM), l-glutamate (1, 2.5, or
      5 mM), l-alpha-aminobutyrate (3.3mM), beta-mercaptoethanol (BME) (25 microM), l
      cysteine and BME, or l-alpha-aminobutyrate and BME. Increases (P < 0.05) in GSH
      concentrations were observed using l-cysteine, 1.0 mM l-glutamate, l-alpha
      aminobutyrate, and l-alpha-aminobutyrate with BME. Oocytes matured with l-alpha
      aminobutyrate and BME had a lower (P < 0.05) occurrence of polyspermy during IVF
      compared to controls and a greater percentage (P < 0.05) of embryos reaching the
      blastocyst stage compared to other treatment groups. For Objective 2, oocytes
      were matured in NCSU 23 or NCSU 23 supplemented with l-alpha-aminobutyrate with
      BME. Embryo cell death was determined using an Annexin V-FITC assay.
      Supplementation had no effect on the time of cell death. Embryo mortality was
      increased (P < 0.05) from 24 to 42 h post-IVF, with the greatest occurrence
      around 36 h. In conclusion, supplementing l-alpha-aminobutyrate and BME into the
      IVM medium increased intracellular GSH concentrations, decreased the occurrence
      of polyspermy during IVF, and increased embryo development parameters during IVC,
      but did not affect cell death during embryo development. The onset of cell death
      occurred from 24 to 42 h post-IVF, with the greatest occurrence around 36 h post
      IVF.

PMID- 15159124
TI  - Effects of levamisole on hyaluronidase activity and sperm characteristics in
      rams.
AB  - The aim of this study was to determine the effects of levamisole on sperm
      characteristics and hyaluronidase activity of blood serum and semen. For this
      purpose, 12 Akkaraman rams (2-3 years old) were used. Levamisole hydrochloride
      was administered orally at a dose of 7.5mg/kg body weights once daily for 2 days.
      Serum and semen samples were collected from the rams at post-treatment 1, 2, 4,
      24, 48, 72, 96, 120, 144, 216, 288 and 384 h and examined for sperm
      characteristics and hyaluronidase activity. The results showed that the use of
      levamisole caused significant (P < 0.01) increase in serum hyaluronidase activity
      at all times except the 72 h, and in semen hyaluronidase activity at 1, 2, 4, 24,
      72, 96 and 120 h compared to the control group. In addition, the levamisole
      caused significant (P < 0.05) decreases in semen volume, sperm motility,
      concentration and total sperm number at all times. There was no correlation
      between semen hyaluronidase activity and the sperm characteristics. In
      conclusion, levamisole did not have any deleterious effect on hyaluronidase
      enzyme. However, the use of this drug in rams during the breeding season is
      harmful due to the decrease of sperm characteristics.

PMID- 15159125
TI  - Parturition in gilts: duration of farrowing, birth intervals and placenta
      expulsion in relation to maternal, piglet and placental traits.
AB  - Large White x Meishan F2 crossbred gilts (n = 57) were observed continuously
      during farrowing while the placentae of their offspring were labeled in order to
      examine the duration of farrowing and placenta expulsion in relation to maternal
      , piglet- and placental traits and the duration of birth interval in relation to
      birth weight, birth order and placental traits. Independently from each other,
      litter size, gestation length and offspring directed aggression significantly (P
      0.05) affected duration of farrowing. An increase in litter size was associated
      with an increase of duration of farrowing and an increase in gestation length was
      associated with a decrease of duration of farrowing. Aggressive gilts took longer
      to farrow, compared to non-aggressive ones. After taking into account litter
      size, gestation length and offspring directed aggression, placental thickness
      (i.e., placental weight corrected for placental surface area) was significantly
      (P < 0.05) related to duration of farrowing, i.e., litters with on average
      thicker placentae took longer to farrow. The latter effect is the result of the
      fact that individual placental thickness significantly (P < 0.01) affected
      individual birth interval, independent of birth weight. The piglet has to break
      its own membranes to be able to start its journey through the uterus towards the
      birth channel. Apparently, a thicker placenta offers more resistance and thus
      prolongs the process of birth. Independent of placental thickness, birth interval
      significantly (P < 0.01) decreased with an increase in birth order (first born to
      last born). The high variation of birth intervals for the last born piglets,
      caused a slight increase in average birth interval for the latter piglets.
      Litters with on average more areolae per placenta took significantly (P < 0.001)
      less time to be born than litters with on average less areolae per placenta
      (independent of total number of piglets born and other placental traits), while
      birth intervals within litters were not affected by this trait. Thus, these
      results are probably due to a gilt trait rather than a piglet trait. Since the
      number of areolae represent the number of uterine glands present, the gilt trait
      might be uterine development. Duration of placenta expulsion significantly (P <
      0.01) increased with an increase of duration of farrowing. Furthermore, the first
      placenta was expelled significantly (P < 0.01) earlier relative to last piglet
      when duration of farrowing was protracted, while there was no relation of the
      time interval between first placenta and last piglet and the duration of placenta
      expulsion. In conclusion, the most important finding of this study is that
      placental thickness rather than birth weight appears to play an important role in
      the duration of birth intervals and as a result, of duration of parturition in
      gilts.

PMID- 15159126
TI  - Vitrification of porcine embryos at various developmental stages using different
      ultra-rapid cooling procedures.
AB  - In this study, three different vitrification systems (open pulled straw: OPS;
      superfine open pulled straw: SOPS; and Vit-Master technology using SOPS: Vit
      Master-SOPS) were compared in order to investigate the influence of cooling rate
      on in vitro development of vitrified/warmed porcine morulae, early blastocysts,
      or expanded blastocysts. Embryos were obtained surgically on Day 6 of the estrous
      cycle (D0 = onset of estrus) from weaned crossbred sows, classified and pooled
      according their developmental stage. A subset of embryos from each developmental
      stage was cultured to evaluate the in vitro development of fresh embryos; the
      remaining embryos were randomly allocated to each vitrification system. After
      vitrification and warming, embryos were cultured in vitro for 96 h in TCM199 with
      10% fetal calf serum at 39 degrees C, in 5% CO(2) in humidified air. During the
      culture period, embryos were morphologically evaluated for their developmental
      progression. The developmental stage of embryos at collection affected the
      survival and hatching rates of vitrified/warmed embryos (P < 0.001). The
      vitrification system or the interaction of vitrification system and developmental
      stage had no effect on these parameters (P > 0.05). Vitrified expanded
      blastocysts showed the best development in vitro (P < 0.001), with survival and
      hatching rates similar to those of fresh expanded blastocysts. The hatching rate
      of fresh morula or early blastocyst stage embryos was higher than their vitrified
      counterparts. In conclusion, under our experimental conditions, cooling rates
      greater than 20,000 degrees C/min, as occurs when SOPS or Vit-Master-SOPS systems
      are used, do not enhance the efficiency of in vitro development of vitrified
      porcine embryos.

PMID- 15159127
TI  - The use of estradiol and/or GnRH in a two-dose PGF protocol for breeding
      management of beef heifers.
AB  - The objective was to determine reproductive performance following AI in beef
      heifers given estradiol to synchronize ovarian follicular wave emergence and
      estradiol or GnRH to synchronize ovulation in a two-dose PGF-based protocol. In
      Experiment 1, 561 cycling (confirmed by ultrasonography), Angus heifers received
      500 microg cloprostenol, i.m. (PGF) twice, 14 days apart (days 0 and 14) and were
      equally allocated to four groups in a 2 x 2 factorial design. On Day 7, heifers
      received either 2 mg estradiol benzoate (EB) and 50 mg progesterone (P), i.m. in
      oil (EBP group) or no treatment (NT group). Half the heifers in each group
      received 1mg EB, i.m. in oil on Day 15 (24h after the second PGF treatment) with
      TAI 28 h later (52 h after PGF), and the other half received 100 microg GnRH,
      i.m. on Day 17 (72 h after PGF) concurrent with TAI. All heifers were observed
      for estrus twice daily from days 13 to 17; those detected in estrus more than 16
      h before scheduled TAI were inseminated 4-16 h later and considered nonpregnant
      to TAI. Overall pregnancy rate (approximately 35 days after AI) was higher in
      heifers that received EBP than those that did not (61.6% versus 48.2%,
      respectively; P < 0.002); but was lower in heifers that received EB after PGF
      than those that received GnRH (50.0% versus 59.8%; P < 0.02). Although estrus was
      detected prior to TAI in 77 of 279 heifers (27.6%) treated with EBP (presumably
      due to induced luteolysis), they were inseminated and 53.2% became pregnant.
      Overall pregnancy rates were 51.4, 68.3, 45.0, and 55.0% in the NT/GnRH,
      EBP/GnRH, NT/EB, and EBP/EB groups, respectively (P < 0.05). In Experiment 2, 401
      cycling, Angus heifers were used. The design was identical to Experiment 1,
      except that 1.5mg estradiol-17beta (E-17beta) plus 50mg progesterone (E-17betaP)
      and 1mg E-17beta were used in lieu of EBP and EB, respectively. All heifers
      receiving E-17beta 24h after the second injection of PGF (NT/E-17beta and E
      17betaP/E-17beta) were TAI 28 h later without estrus detection, i.e. 52 h after
      PGF. Heifers in the other two groups received 100 microg GnRH, i.m. 72 h after
      PGF and were concurrently TAI; heifers in these two groups that were detected in
      estrus prior to this time were inseminated 4-12h later and considered nonpregnant
      to TAI. Estrus rate during the first 72 h after the second PGF treatment was
      higher (P < 0.05) in the E-17betaP/GnRH group (45.0%; n = 100) than in the
      NT/GnRH group (16.0%; n = 100), but conception rate following estrus detection
      and AI was not different (mean, 57.4%; P = 0.50). Overall pregnancy rate was not
      significantly different among groups (mean, 46.9%; P = 0.32). In summary, the use
      of EB or E-17beta to synchronize follicular wave emergence and estradiol or GnRH
      to synchronize ovulation in a two-dose, PGF-based protocol resulted in acceptable
      fertility to TAI. However, when 2mg EB was used to synchronize follicular wave
      emergence, early estrus occurred in approximately 28% of heifers, necessitating
      additional estrus detection. A combination of estrus detection and timed-AI in a
      two-dose PGF protocol resulted in highly acceptable pregnancy rates.

PMID- 15159128
TI  - Lobeline produces conditioned taste avoidance in rats.
AB  - Previous results indicate that pretreatment with lobeline attenuates
      methamphetamine (METH) self-administration in rats, but not by acting as a
      substitute reinforcer. Given these findings, it has been suggested that lobeline
      may serve as a useful pharmacotherapy for psychostimulant abuse. However, because
      lobeline produces emesis and nausea in humans, the present study examined whether
      lobeline has direct effects on taste avoidance behavior in rats within the same
      dose range shown previously to decrease METH self-administration. Two experiments
      utilized a Pavlovian conditioning procedure to determine if lobeline produces
      conditioned taste avoidance (CTA) in rats. In Experiments 1 and 2, rats consumed
      either novel milk or salt solutions, respectively, and within 10 min, were
      injected with lobeline (0.3-3.0 mg/kg) or METH (0.3-3.0 mg/kg). A single-bottle
      test conducted 48 h after flavor-drug pairings indicated that the dose of
      lobeline that reduced METH self-administration in a previous study (i.e., 3.0
      mg/kg) also produced reliable CTA for milk and salt solution. These findings
      suggest a need to develop lobeline analogs that reduce METH self-administration,
      but do not produce CTA following the consumption of a novel solution.

PMID- 15159129
TI  - Antidepressant- and anxiolytic-like activity of magnesium in mice.
AB  - The antidepressant- and anxiolytic-like effects of magnesium, an N-methyl-d
      aspartate (NMDA) glutamate receptor inhibitor, were studied in mice using the
      forced swim test and elevated plus-maze test, respectively. The doses of 20 and
      30 mg Mg/kg, reduced immobility time in the forced swim test exerting
      antidepressant-like activity. In the elevated plus-maze test, magnesium at the
      same doses produced anxiolytic-like effect. The doses of magnesium active in both
      tests did not affect locomotor activity. To evaluate the tolerance to these
      effects, we also performed experiments on the following acute/chronic magnesium
      treatment schedule: chronic saline and saline challenge at 0.5 h before
      behavioral experiments or serum magnesium determination (S+S), chronic saline and
      magnesium challenge (S+Mg), chronic magnesium and saline challenge (Mg+S),
      chronic magnesium and magnesium challenge (Mg+Mg). The antidepressant- and
      anxiolytic-like effect of magnesium was demonstrated in groups treated acutely
      and chronically with magnesium (Mg+Mg), but not in the Mg+S group. Moreover,
      these effects seem to be connected with at least 58% increase in serum magnesium
      concentration. The results indicate that magnesium induces the antidepressant-
      and anxiolytic-like effects without tolerance to these activities, which suggests
      a potential antidepressant and anxiolytic activity of magnesium in these
      disorders in humans.

PMID- 15159130
TI  - Sex differences in voluntary oral nicotine consumption by adolescent mice: a dose
      response experiment.
AB  - Recent studies with adolescent rodents offer valuable information regarding the
      neurochemical and behavioral effects of adolescent nicotine exposure. One hundred
      twenty-one male and 125 female adolescent (35 days of age) C57BL/6J mice were
      tested for voluntary nicotine consumption by providing 24-h access to both
      saccharin-only (SAC) and one of six nicotine-containing solutions [10, 25, 50,
      75, 100, 200 ug (-)-freebase nicotine/ml in 2% SAC] in the home cage for 7 days.
      Although males and females drank similar volumes (ml) of nicotine, the female
      mice consumed more nicotine adjusted for body weight (mg/kg) and as a percentage
      of total fluid intake than did the male mice. In contrast, there was no sex
      difference in overall serum cotinine levels (adjusted for liver weight). For all
      mice, nicotine consumption and serum cotinine levels increased in a dose
      dependent manner, and the volume of nicotine intake (ml), percent nicotine
      intake, and nicotine dosage (mg/kg) on the last day of the experiment were
      positively correlated with cotinine levels. Cotinine levels were inversely
      related to body weight only for females. Sex differences in nicotine consumption,
      but not in cotinine levels, suggest sex differences in pharmacokinetic processes
      that may contribute to oral nicotine consumption behavior during periadolescence.

PMID- 15159131
TI  - Antianxiety and antidepressant effects of riparin III from Aniba riparia (Nees)
      Mez (Lauraceae) in mice.
AB  - This work presents behavioral effects of methyl ethers of N-(2,6
      dihydroxybenzoyl) tyramine (riparin III) isolated from the unripe fruit of Aniba
      riparia on the open field, elevated plus maze (EPM), rotarod, hole board,
      barbiturate-induced sleeping time, tail suspension and forced swimming tests in
      mice. Riparin III was administered intraperitoneally to male mice at single doses
      of 25 and 50 mg/kg. The results showed that riparin III with both doses had no
      effects on spontaneous motor activity in mice or in the rotarod test, but
      decreased the number of grooming and rearing. At the dose of 50 mg/kg, riparin
      III increased the number of entries in the open arms of the EPM test as compared
      with control. Similarly, in the hole-board test, both doses increased the number
      of head dips. There was a reduction on the sleeping latency with both doses and a
      prolongation of the pentobarbital-induced sleeping time with the dose of 25
      mg/kg. In the tail suspension test, similar to imipramine (30 mg/kg), riparin III
      at the dose of 50 mg/kg presented a reduction in the immobility time. In the
      forced swimming test, both doses of riparin III decreased the immobility time.
      These results showed that riparin III potentiated the barbiturate-induced
      sleeping time and presented antidepressant- and anxiolytic-like effects.

PMID- 15159132
TI  - Spermidine/spermine N1-acetyltransferase overexpression in mice induces
      hypoactivity and spatial learning impairment.
AB  - The present work addresses the role of polyamines in learning and general
      behavior by subjecting transgenic mice overexpressing polyamine catabolic enzyme,
      spermidine/spermine N(1)-acetyltransferase (SSAT) and their syngenic littermates
      to neurobehavioral profiling assessment (SHIRPA) and to radial eight-arm maze.
      The general health and physiological conditions as well as the entire behavioral
      battery comprising of 34 parameters were recorded. The eight-arm radial maze (8
      RAM) task included an initial acquisition task for 9 days followed by a 2-day
      retention test after a 2-week break. In addition, blood samples were taken for
      hormone analysis. Transgenic mice, which showed reduced motor activity,
      aggression and muscle tone, spent more time in the radial maze during initial
      acquisition and retention tasks as compared with syngenic mice. Moreover, the
      learning performance of transgenic females was significantly inferior to syngenic
      females. Interestingly, the levels of several hormones were significantly altered
      in SSAT transgenic mice; circulating adrenocorticotropic hormone (ACTH) and
      corticosterone levels were markedly increased while testosterone and thyroidal
      hormone levels were decreased. These changes may be related to the dramatic
      increase in brain putrescine levels in SSAT-overexpressing (SSAT-OE) mice, but it
      is likewise possible that the behavioral changes and learning impairment are
      attributable to more peripheral mechanisms (such as alterations in steroid
      hormone metabolism), which in turn, could be a consequence of the disturbed
      polyamine homeostasis.

PMID- 15159133
TI  - Effect of acute and chronic olanzapine treatment on phencyclidine-induced
      behavioral sensitization in rats with neonatal dopamine loss.
AB  - In agreement with previous work, adult rats given selective lesions to dopamine
      (DA)-containing neurons as neonates exhibited a greater behavioral sensitization
      to repeated phencyclidine (PCP) treatment in comparison to sham-lesioned
      controls. Acute administration of olanzapine (1-5 mg/kg ip) or clozapine (15
      mg/kg ip) decreased sensitized PCP-induced activity in both lesioned and control
      animals. Acute haloperidol (0.5 mg/kg ip) had no impact on PCP responsiveness in
      lesioned animals, but significantly antagonized PCP effects in sham-lesioned
      controls. Ketanserin, a selective 5-HT(2A)/5-HT(2C)-receptor antagonist,
      significantly reduced PCP activation in both lesioned and control rats,
      suggesting that the efficacy of atypical antipsychotics against PCP-induced
      sensitized responses may be mediated by one of the 5-HT(2)-receptor subtypes. A 6
      week chronic regimen of orally administered olanzapine, clozapine, or haloperidol
      failed to block the sensitization induced by repeated PCP exposure. However, a 10
      month oral olanzapine treatment significantly blunted the behavioral
      sensitization to repeated PCP exposure in lesioned animals, even after withdrawal
      from chronic olanzapine for more than 3 weeks. A 10-month oral haloperidol
      treatment had no effect on the sensitization induced by repeated PCP dosing. The
      persistent effect of chronic olanzapine administration on PCP sensitization may
      be relevant to the chronic therapeutic efficacy of atypical antipsychotics
      treating schizophrenia-a clinical syndrome linked to enhanced sensitivity to N
      methyl-d-aspartate (NMDA)-receptor antagonists.

PMID- 15159134
TI  - Assessing subjective and psychomotor effects of the herbal medication valerian in
      healthy volunteers.
AB  - Valerian is the common name given to the genus Valeriana, an odiferous,
      herbaceous perennial plant widely distributed in the temperate regions of Asia,
      Europe, and North America. It is among the most widely used herbal medicines in
      the world. Numerous clinical studies have demonstrated valerian's ability to
      improve sleep; however, to the best of our knowledge, no study has systematically
      assessed subjective and psychomotor/cognitive effects of valerian in young
      healthy adults across a range of doses. In the present study, we sought to
      determine whether valerian extract (Valeriana officinalis) altered mood and/or
      impaired psychomotor/cognitive performance in young healthy volunteers. We
      examined the effects of valerian extract (600, 1200, and 1800 mg) and 10 mg
      diazepam (positive control) compared to placebo in 10 young healthy volunteers.
      Dependent measures included subjective and psychomotor variables. The valerian
      extract had no significant effects on any of the dependent measures. Diazepam,
      though, produced subjective effects as measured by four different rating scales,
      and impaired psychomotor/cognitive performance. The data suggest that acute
      administration of valerian does not have mood-altering or psychomotor/cognitive
      effects in young healthy volunteers.

PMID- 15159135
TI  - Sedative and motor-impairing effects of neuropeptide Y and ethanol in selectively
      bred P and NP rats.
AB  - Past findings suggest a positive association between endogenous neuropeptide Y
      (NPY) activity and ethanol-induced sedation, and there is evidence for additive
      effects of administered NPY with sedative-hypnotics. The present investigation
      examined the effects of intracerebroventricular NPY injection on ethanol-induced
      sedation and motor impairment in selectively bred alcohol-preferring (P) and 
      nonpreferring (NP) rats. In Experiment 1, P and NP rats were assessed for loss
      and recovery of righting reflex (RR) following infusion with either NPY (10.0
      microg) or aCSF followed by ethanol injection (2.5 g/kg ip). NPY reduced time to
      lose RR and increased time to regain RR similarly in P and NP rats. Blood-ethanol
      levels (BELs) were lower at time of recovery in NPY-treated rats relative to aCSF
      controls. Thus, NPY enhanced ethanol-induced sedation. In Experiment 2, P and NP
      rats pretreated with either saline or ethanol (1.0 g/kg ip) were assessed for
      motor activity following infusion with either NPY (2.5, 5.0, or 10.0 microg) or
      aCSF. Ethanol alone and NPY alone suppressed motor activity, but there were no
      additive effects between the two. Taken together, these results provide partial
      support for past observations of additivity between NPY and drug-induced
      sedation, and suggest a role for NPY in the neurobehavioral effects of acute
      ethanol exposure.

PMID- 15159136
TI  - Susceptibility to audiogenic seizure and neurotransmitter amino acid levels in
      different brain areas of IL-6-deficient mice.
AB  - Interleukin-6-deficient (IL-6(-/-)) mice and their normal littermate (WT) were
      studied to evaluate their susceptibility to seizures induced by electroshock and
      audiogenic stimuli at different ages. No significant changes in maximal
      electroshock susceptibility were evidenced between the two strains, while
      audiogenic seizures (AGS) can be induced only in IL-6(-/-) mice. The effects of
      age and genetic condition on AGSs were evaluated. The behavioural and
      electrocortical changes during audiogenic stimulus were observed. In addition,
      the levels of neurotransmitter amino acids in five brain areas (of both strains)
      were measured at 60 days of age. Aspartate level significantly increased in the
      brain stem (BS) and hippocampus (HI), while it decreased in the diencephalon (DE)
      of IL-6(-/-) mice. Glutamate content significantly decreased in the cerebellum
      (CB), DE and HI. GABA levels significantly decreased in all the areas studied.
      Glycine significantly decreased in the BS, CB and DE, while taurine decreased
      only in the DE. The levels of glutamine significantly decreased in all the areas
      examined, except in the cortex (CX). The changes of neuroactive amino acid
      levels, particularly in the BS, might explain the characteristic of high
      propensity to AGS of IL-6(-/-) mice. The present data support the validity of IL
      6(-/-) mice as a novel epileptic model for the study of the pathophysiology and
      pharmacology of epilepsy.

PMID- 15159137
TI  - GABAA receptors modulate cannabinoid-evoked hypothermia.
AB  - Cannabinoids evoke hypothermia by stimulating central CB(1) receptors. GABA
      induces hypothermia via GABA(A) or GABA(B) receptor activation. CB(1) receptor
      activation increases GABA release in the hypothalamus, a central locus for
      thermoregulation, suggesting that cannabinoid and GABA systems may be
      functionally linked in body temperature regulation. We investigated whether GABA
      receptors modulate the hypothermic actions of [4,5-dihydro-2-methyl-4(4
      morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one]
      (WIN 55212-2), a selective cannabinoid agonist, in male Sprague-Dawley rats. WIN
      55212-2 (2.5 mg/kg im) produced a rapid hypothermia that peaked 45-90 min
      postinjection. The hypothermia was attenuated by bicuculline (2 mg/kg ip), a
      GABA(A) antagonist. However, SCH 50911 (1-10 mg/kg ip), a GABA(B) blocker, did
      not antagonize the hypothermia. Neither bicuculline (2 mg/kg) nor SCH 50911 (10
      mg/kg) by itself altered body temperature. We also investigated a possible role
      for CB(1) receptors in GABA-generated hypothermia. Muscimol (2.5 mg/kg ip), a
      GABA(A) agonist, or baclofen (5 mg/kg ip), a GABA(B) agonist, evoked a
      significant hypothermia. Blockade of CB(1) receptors with SR141716A (2.5 mg/kg
      im) did not antagonize muscimol- or baclofen-induced hypothermia, indicating that
      GABA-evoked hypothermia does not contain a CB(1)-sensitive component. Our results
      implicate GABA(A) receptors in the hypothermic actions of cannabinoids and
      provide further evidence of a functional link between cannabinoid and GABA
      systems.

PMID- 15159138
TI  - Intranasal cocaine in humans: acute tolerance, cardiovascular and subjective
      effects.
AB  - Although recent research has focused on "crack" cocaine, the majority of the
      cocaine users in the United States insufflate ("snort") cocaine rather than smoke
      it. Furthermore, the intranasal route of administration is often the first way
      that many cocaine-dependent individuals used cocaine. Numerous studies have
      reported on the effects of repeated doses of smoked or intravenous cocaine, the
      relationship between cocaine plasma level and cocaine's effects, and the
      development of acute tolerance to smoked or intravenous cocaine. Significantly
      less information is available about similar effects of intranasal cocaine. The
      purpose of this study was to determine the dose-dependent effects of repeated
      intranasal cocaine in humans. Ten experienced male cocaine users were admitted to
      the hospital on two separate occasions for four days each, with a minimal two
      week interval between admissions. During each admission, an intranasal cocaine
      (0.06, 0.34, 0.69, and 1.37 mg/kg) dose-response curve was determined during four
      laboratory sessions: Two administrations of the same cocaine dose occurred each
      session at 40-min intervals. Intranasal cocaine produced dose-related increases
      in ratings of "positive" drug effects, heart rate, and blood pressure. Plasma
      cocaine levels peaked following the second cocaine insufflation of each session,
      while metabolite levels increased during each session. Although the plasma
      cocaine level approximately doubled following the second cocaine administration,
      the ratings of positive drug effects, heart rate, and blood pressure did not
      increase after the second cocaine administration. These data demonstrate that, as
      observed with smoked and intravenous cocaine, acute within-session tolerance
      develops during repeated intranasal cocaine administration.

PMID- 15159139
TI  - Effect of felbamate and its combinations with conventional antiepileptics in
      amygdala-kindled rats.
AB  - We investigated the effect of felbamate, administered singly and in combination
      with carbamazepine, phenobarbital, phenytoin or clonazepam, on various behavioral
      and electrographic correlates of seizures in amygdala-kindled rats. Felbamate (5
      or 10 mg/kg) significantly increased afterdischarge threshold, shortened seizure
      and afterdischarge durations but remained without effect on seizure severity.
      Furthermore, the combination of felbamate (2.5 mg/kg) with carbamazepine (7.5
      mg/kg; both drugs at their subeffective doses), was associated with the reduction
      in seizure severity and afterdischarge duration. In relation to the
      afterdischarge duration, the antiseizure potency of felbamate and carbamazepine,
      in combination, was comparable with that of carbamazepine (10 mg/kg) administered
      alone. Neither carbamazepine (7.5 and 10 mg/kg) nor felbamate (2.5-10 mg/kg)
      affected seizure severity, whereas the combined administration of felbamate (2.5
      mg/kg) with carbamazepine (7.5 mg/kg) led to significant reduction in seizure
      severity from the fifth to the third stage of Racine's scale. Among the
      conventional antiepileptic drugs evaluated in this study, only valproate (100
      mg/kg) and clonazepam (0.1 mg/kg) exerted similar action on seizure severity.
      However, the combinations of felbamate (2.5 mg/kg), with subeffective doses of
      valproate, phenobarbital, phenytoin or clonazepam, were not associated with any
      protective action. As blood and brain felbamate and carbamazepine concentrations
      were unaffected, a pharmacokinetic interaction can be excluded and a
      pharmacodynamic interaction concluded. These data suggest that felbamate and
      carbamazepine, administered in combination, may be useful in patients with drug
      resistant partial epilepsy.

PMID- 15159140
TI  - Normal spatial and contextual learning for ketamine-treated rats in the
      pilocarpine epilepsy model.
AB  - Cognitive impairments frequently accompany epileptic disorders. Here, we examine
      two neuroprotective agents, the noncompetitive NMDA antagonist ketamine and the
      dopaminergic antagonist acepromazine, for their efficacy in attenuating cognitive
      impairments in the lithium-pilocarpine (LI-PILO) model of rat limbic epilepsy.
      Declarative-like cognitive behaviors were assessed in a Morris water maze task
      that consisted successively of spatial and nonspatial (cued platform) training.
      Whereas the ketamine-treated (Ket) LI-PILO rats performed equally in all respects
      to nonseized control rats for the spatial and nonspatial components of the water
      maze task, the acepromazine-treated (Ace) LI-PILO rats failed to demonstrate
      learning in either the hidden or cued platform variants of the task and did not
      demonstrate any place learning in the platform-removed probe trials. We further
      assessed nondeclarative (associative) cognitive behaviors with a standard
      contextual fear-conditioning protocol. LI-PILO rats treated with acepromazine
      failed to learn the Pavlovian relationship; Ket LI-PILO rats performed
      equivalently to nonseized controls. Cumulatively, these data suggest robust
      cognitive sparing for LI-PILO rats with pharmacological NMDA receptor antagonism
      following induction of status epilepticus (SE). This cognitive sparing occurs
      despite earlier findings that the mean amount of total brain damage with LI-PILO
      is equivalent for Ket and Ace rats.

PMID- 15159141
TI  - Chronic aspartame affects T-maze performance, brain cholinergic receptors and
      Na+,K+-ATPase in rats.
AB  - This study demonstrated that chronic aspartame consumption in rats can lead to
      altered T-maze performance and increased muscarinic cholinergic receptor
      densities in certain brain regions. Control and treated rats were trained in a T
      maze to a particular side and then periodically tested to see how well they
      retained the learned response. Rats that had received aspartame (250 mg/kg/day)
      in the drinking water for 3 or 4 months showed a significant increase in time to
      reach the reward in the T-maze, suggesting a possible effect on memory due to the
      artificial sweetener. Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label
      muscarinic cholinergic receptors and atropine (10(-6) M) to determine nonspecific
      binding in whole-brain preparations, aspartame-treated rats showed a 31% increase
      in receptor numbers when compared to controls. In aspartame-treated rats, there
      was a significant increase in muscarinic receptor densities in the frontal
      cortex, midcortex, posterior cortex, hippocampus, hypothalamus and cerebellum of
      80%, 60%, 61%, 65%, 66% and 60%, respectively. The midbrain was the only area
      where preparations from aspartame-treated rats showed a significant increase in
      Na(+),K(+)-ATPase activity. It can be concluded from these data that long-term
      consumption of aspartame can affect T-maze performance in rats and alter receptor
      densities or enzymes in brain.

PMID- 15159142
TI  - Aphrodisiac properties of Montanoa tomentosa aqueous crude extract in male rats.
AB  - Cihuapatli, the Mexican zoapatle (Montanoa tomentosa) has an extensive
      ethnomedical history of use as a traditional remedy for reproductive impairments.
      During the study of the ejaculatory function in rats and by testing a set of
      Mexican plants with medicinal properties, we observed that crude extracts of M.
      tomentosa facilitated ejaculation. Thus, we decided to analyze the possibility
      that this plant possessed sexual stimulant properties. To that aim, copulatory
      behavior of sexually active male rats receiving doses of 38, 75 and 150 mg/kg of
      the aqueous crude extract of M. tomentosa, as it is prepared in traditional
      medicine, was assessed. In addition, we evaluated the effect of the 75-mg/kg dose
      of the extract on males with anesthetization of the genital area and on sexual
      behavior of sexually inactive male rats (noncopulators). Results showed that
      acute oral administration of crude extracts of M. tomentosa facilitates
      expression of sexual behavior in sexually active male rats, significantly
      increases mounting behavior in genitally anesthetized animals and induces the
      expression of sexual behavior in noncopulating males. Altogether, these data
      reveal a facilitatory action of this extract on sexual activity and particularly
      on sexual arousal. Present findings provide experimental evidence that the crude
      extract preparation of M. tomentosa, used as a traditional remedy, possesses
      aphrodisiac properties.

PMID- 15159143
TI  - The role of alpha-adrenoceptor mechanism(s) in morphine-induced conditioned place
      preference in female mice.
AB  - It has been shown that the alpha-adrenergic system is involved in some effects of
      opioids, including analgesia and reward. Gender differences also exist between
      males and females in response to alpha-adrenergic agents. This study was designed
      to determine the effects of alpha-adrenoceptor agonists and antagonists on the
      acquisition or expression of morphine-induced conditioned place preference (CPP)
      in female mice. The experiments showed that subcutaneous injections of morphine
      (0.5-8 mg/kg) induced CPP in a dose-dependent manner in mice. Intrapritoneal
      administration of the alpha-1-adrenoceptor agonist, phenylephrine (0.03, 0.1 and
      0.3 mg/kg), and alpha-2 adrenoceptor agonist, clonidine (0.0001, 0.0005 and 0.001
      mg/kg), as well as alpha-1-adrenoceptor antagonist, prazosin (0.01, 0.05 and 0.1
      mg/kg) or alpha-2 adrenoceptor antagonist, yohimbine (0.005, 0.01 and 0.05 mg/kg)
      did not induce motivational effects and also did not alter locomotor activity in
      the animals. In the second set of experiments, the drugs were used before testing
      on Day 5, to test their effects on the expression of morphine-induced CPP.
      Intrapritoneal administration of phenylephrine and clonidine decreased the
      expression of morphine-induced CPP. In contrast, after application of prazosin or
      yohimbine, the expression of morphine-induced CPP was increased. Administration
      of lower (0.03 mg/kg) and higher doses of phenylephrine (0.1 and 0.3 mg/kg)
      during acquisition of morphine CPP decreased and increased the morphine CPP,
      respectively. Similarly, the administration of prazosin and clonidine decreased
      while yohimbine increased the morphine CPP. It may be concluded that alpha
      adrenoceptor mechanism(s) influence morphine-induced CPP in female mice.

PMID- 15159144
TI  - Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse
      model of Parkinson's disease.
AB  - The biochemical, behavioral and immunohistochemical manifestations were
      investigated in mice subjected to four experimental schedules with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) hydrochloride treatment. The mice were
      treated intraperitoneally with MPTP (20 mg/kg in saline) four times a day at 2-h
      intervals showed severe and persistent depletions of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum
      and behavioral deficits, as compared with those (1) treated with MPTP (15 mg/kg
      in saline ip) once a day for 14 consecutive days; (2) MPTP (30 mg/kg in saline
      ip) twice a day for five consecutive days; and (3) MPTP (10 mg/kg in saline ip)
      four times a day at 1-h intervals for two consecutive days. The
      immunohistochemical study has shown that the acute treatment with MPTP caused
      severe loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)
      immunoreactive dopaminergic neurons and marked increase in glial fibrillary
      acidic protein (GFAP)-immunoreactive astrocytes in the striatum and the
      substantia nigra. Thus acute treatment of mice with MPTP was accompanied by
      sustained nigral degeneration and motor abnormalities. Furthermore, our results
      with Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase
      (Mn-SOD) immunostainings suggest that altered capacity of free radicals quenching
      may play a key role in the development of the neurons and interneuron damage
      after MPTP neurotoxicity. Thus, our findings provide valuable information on age
      related disease progression and mechanisms of neurodegeneration.

PMID- 15159145
TI  - Delay fear conditioning modifies phospholipase C-beta 1a signaling in the
      hippocampus and frontal cortex.
AB  - The use of the single-trial fear conditioning paradigm allows for control over
      the exact moment when an animal is exposed to a learning event, making it
      possible to study both the initial neurobiological changes that are associated
      with learning and changes that take place over long periods of time. In the
      present study, we performed detailed analyses of the alterations in
      phosphatidylinositol-specific phospholipase C-beta1a (PLC-beta1a) levels and
      enzyme activities in subcellular fractions prepared from the hippocampal
      formation (HPF) and medial frontal cortex (MFC) 1, 3, 5, 7, 24, and 72 h
      following single-trial fear conditioning. We observed tissue- and time-dependent
      changes in both PLC-beta1a enzyme activity and anti-PLC-beta1a immunoreactivity
      in each subcellular fraction. Based on these observations, we hypothesize that
      changes in PLC-beta1a catalytic activity and subcellular distribution play
      important roles in neuronal signaling processes that are required for fear
      conditioned learning and memory.

PMID- 15159146
TI  - Antidepressant-like effects of the acute and chronic administration of nicotine
      in the rat forced swimming test and its interaction with fluoxetine [correction
      of flouxetine].
AB  - An antidepressant action of nicotine (NIC) has recently been suggested.
      Flouxetine, a selective serotonin reuptake inhibitor, is currently the most
      widely used antidepressant. In the present study, we analyzed the effects of the
      administration of NIC, fluoxetine (FLX), and the combination of both drugs given
      acutely, subchronically, and chronically as well as 7 days after chronic
      administration of these drugs on the forced swim test. Results showed that NIC
      induced a significant reduction of the time in immobility during the forced swim
      test (antidepressant effect), with a concomitant increase in swimming activity
      (serotonergic activation), after acute administration. These effects remain the
      same after subchronic and chronic administration. FLX failed to induce any effect
      after acute administration but did induce a significant decrease of immobility
      and an increase of swimming after subchronic administration. The effect of the
      chronic administration was significantly larger compared to subchronic
      administration. The combination of both drugs induced a larger effect than that
      observed after a single administration but only after subchronic treatment. No
      effect was observed after the end of the 7-day treatments. Data suggest that NIC
      has an antidepressant action that is expressed faster than FLX but remains the
      same later. Thus, cholinergic-serotonergic interactions could play an important
      role in the treatment of depression.

PMID- 15159147
TI  - Morphine and endomorphin-1 differently influence pronociceptin/orphanin FQ system
      in neuropathic rats.
AB  - In the present study, we investigated the influence of intrathecal (i.t.)
      administration of morphine and endomorphin-1 on the level of
      pronociceptin/orphanin FQ and opioid receptor-like 1 (ORL1) receptor mRNAs in the
      lumbar part of the spinal cord in the rat model of neuropathic pain. The ligation
      of the sciatic nerve did not change the levels of pronociceptin/orphanin FQ and
      ORL1 receptor mRNAs in laminae I-VI of the dorsal horn when measured by in situ
      hybridisation 2 and 7 days after the nerve injury, but ORL1 receptor mRNA level
      in the ventral horn was significantly increased. Two micro-opioid receptor
      agonists, morphine and endomorphin-1, whose effectiveness in neuropathic pain is
      different, also disparately influenced nociceptin/orphanin FQ system in this pain
      model, inasmuch as an increase in pronociceptin/orphanin FQ and ORL1 receptor
      mRNAs was observed in laminae I-VI after morphine administration (5 microg i.t.)
      but not after endomorphin-1 treatment (5 microg i.t.). Moreover, the injection of
      ORL1 receptor antagonists (PhePsi; 30 microg i.t.) before morphine potentiated
      the effect of morphine in neuropathic pain model. Therefore, the activation of
      the endogenous nociceptin/orphanin FQ system, which is known to exhibit
      antiopioidergic activity, apart from its analgesic action, could be the reason
      for lower responsiveness to morphine in neuropathic pain.

PMID- 15159148
TI  - Early administration of nicotinamide prevents learning and memory impairment in
      mice induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine.
AB  - BACKGROUND AND PURPOSE: NAD has been reported to improve the dementia of the
      Alzheimer type or sensory register, short- and long-term memory loss in the aged.
      Although nicotinamide has been confirmed to decrease infarct volumes and
      neurological deficit findings in several animal stroke models, it is not clear
      whether its neuroprotective effects can prevent memory damage sequelae. METHODS:
      We have addressed this topic by designing two behavioral paradigms. A memory
      impairment and cognitive change model was used in mice following 1-methyl-4
      phenyl-l, 2, 3, 6-tetrahydropyridine (MPTP) exposure. Step-down and step-through
      tests were performed to examine the effects of nicotinamide on learning and
      memory impairment. RESULTS: It was found that the early administration of
      nicotinamide (2 h after the injection of MPTP) could decrease error numbers,
      lessen stimulation time and prolong residence duration on the safety platform in
      the step-down test. Delayed administration of nicotinamide resulted in decreased
      effects. Similar results were found in the step-through test. Nicotinamide
      administrated 12 h after the induction of a memory-impairment model still exerted
      its effects on memory dysfunction. CONCLUSIONS: The injection of MPTP can cause a
      loss of brain functions including learning and memory. Learning and memory
      dysfunction probably occurs secondary to damage to arterioles and dopaminergic
      neurons by MPTP. By inhibiting oxidative stress, increasing NAD synthesis and ATP
      production and inhibiting poly (ADP-ribose) polymerase, nicotinamide is known to
      rescue the still viable, but injured, cells. This rescue process may partially
      restore learning and memory.

PMID- 15159149
TI  - Effects of oxazepam on methamphetamine-induced conditioned place preference.
AB  - Our laboratory has been investigating the role for the hypothalamo-pituitary
      adrenal (HPA) axis and benzodiazepines in the behavioral effects of cocaine for
      several years now. The following represents our initial investigation of the
      influence of benzodiazepines on methamphetamine reward using conditioned place
      preference. In these experiments, methamphetamine (0.5 mg/kg ip) resulted in a
      robust conditioned place preference that was attenuated when the rats were
      pretreated with oxazepam (10 mg/kg ip) on the day of preference testing. These
      data suggest a potential role for benzodiazepines in the behavioral effects of
      methamphetamine. Additional research will be necessary to determine if the nature
      of these effects is similar with what has been observed with cocaine.

PMID- 15159150
TI  - Disinfectant decay and disinfection by-products formation model development:
      chlorination and ozonation by-products.
AB  - Comprehensive disinfectant decay and disinfection by-product formation (D/DBP)
      models in chlorination and ozonation were developed to apply to various types of
      raw and treated waters. Comparison of several types of models, such as empirical
      power function models and empirical kinetic models, was provided in order to
      choose more robust and accurate models for the D/DBP simulations. An empirical
      power function model based on dissolved organic carbon and other parameters
      (Empirically based models for predicting chlorination and ozonation by-products:
      haloacetic acids, chloral hydrate, and bromate, EPA Report CX 819579, 1998)
      showed a strong correlation between measured and predicted trihalomethane (THM)
      and haloacetic acid (HAA) formation for raw waters. Internal evaluation of
      kinetic-based models showed good predictions for chlorine decay and THM/HAA
      formation, but no significant improvements were observed compared to the
      empirical power function model simulations. In addition, several empirical models
      for predicting ozone decay and bromate (ozonation disinfection by-product)
      formation were also evaluated and/or developed. Several attempts to develop
      kinetic-based and alternative models were made: (i) a two-stage model (two
      separate decay models) was adapted to ozone decay and (ii) an ozone demand model
      was developed for bromate formation. Generally, internal evaluation of kinetic
      based models for ozone decay showed significant improvements, but no significant
      improvements for the simulation of bromate formation were observed compared to
      the empirical power function model simulations. Additional efforts were performed
      to reduce the gaps between specific models and their actual application. For
      instance, temperature effects and configuration of ozone contactors were
      considered in actual application.

PMID- 15159151
TI  - Effects of substrate loading rate on biofilm structure.
AB  - The effects of substrate surface loading rate on biofilm growth and structure
      were investigated by chemical, biochemical and microscopic methods. Three tubular
      reactors were operated at equal C:N ratio of 0.1, with substrate loading rates of
      1.2, 0.6 and 0.3g-C/m(2)/day. Substrate loading positively influenced the biofilm
      growth rate. Denser biofilms with lower porosities were formed at higher
      substrate loading. Slowly growing biofilms having porous structures were found to
      have higher specific activities. Nitrification was suppressed under the higher
      substrate loading conditions even at the equal C:N ratio of 0.1, thus proving
      that the spatial competition between nitrifiers and heterotrophs as one limiting
      criteria for stable nitrification. The spatial organization of the ammonia
      oxidizers was biofilm structure related. The strain variability of ammonia
      oxidizers was substrate loading dependent. These findings suggest that substrate
      loading is a key parameter in determining biofilm structure and function.

PMID- 15159152
TI  - Membrane gas transfer under conditions of creeping flow: modeling gas composition
      effects.
AB  - A computational model was developed to predict gas transfer and gas composition
      changes in membrane modules designed for addition of gases to groundwater. The
      model was verified using pilot-scale gas transfer experiments. The modeling and
      experimental results suggest that back diffusion of dissolved gases into the
      membrane has a significant effect on gas transfer via hollow-fiber membrane. In
      the experimental study, N(2) back-diffusion reduced the partial pressure of O(2)
      within the membrane and decreased the concentration gradient for gas transfer.
      The model was able to simulate both the dynamic and steady-state gas transfer
      behavior of the membranes under a variety of operating conditions. This model can
      be used to estimate gas transfer as a function of different membrane module
      design and operating conditions.

PMID- 15159153
TI  - Modeling the sorption kinetics of divalent metal ions to hematite.
AB  - The sorption kinetics of the divalent metals Zn, Co, Ni, and Cd to hematite were
      studied in single sorbate systems with high sorbate/sorbent ratios (from 1.67 to
      3.33mol sorbate/mol sorption sites) in 10mM Na-piperazine N,N'-bis 2-ethane
      sulfonic acid (Na-PIPES) solution at pH 6.8. The experimental data showed a rapid
      initial sorption (half-time about 1min) followed by slower sorption that
      continued for 1-5 days. The sequence of fast to slow sorption kinetics was
      modeled by slow inner-sphere (IS) complexation in equilibrium with outer-sphere
      (OS) complexes. Although the OS reaction was fast and considered to be in
      equilibrium, the extent of OS complexation changed over time due to increased
      surface potential from the IS complexes. For example, the model showed that the
      dimensionless OS complexation function, K(os), decreased from 0.014 initially to
      0.0016 at steady state due to sorption of 4x10(-5)M Zn(II) to 2gL(-1) hematite.
      Sorption rate constants, k(ads), for the various divalent metals ranged from 6.1
      to 82.5M(-1)s(-1). Desorption rate constants, k(des), ranged from 5.2x10(-7) to
      6.7x10(-5)s(-1). This study suggests that the conversion from OS to IS complex
      was the rate-determining step for the sorption of divalent metals on crystalline
      adsorbents.

PMID- 15159154
TI  - Making chlorine greener: investigation of alternatives to sulfite for
      dechlorination.
AB  - Inorganic and organic chloramines pose a threat to aquatic ecosystems that are
      exposed to discharges of treated and disinfected wastewater. Conventionally
      practiced dechlorination with sulfite reduces the most refractory organic
      chloramines too slowly to produce wastewater effluents that meet current
      ecosystem protection criteria in the United States (i.e. total residual chlorine
      < or =0.011mg Cl(2)/L in freshwaters). Seeking faster dechlorinating agents, we
      have measured the rates that four test chloramines (NH(2)Cl, N-Cl-piperidine, N
      Cl-leucylalanine and N-Cl-alanylalanine) react with 10 selected reducing agents
      at pH 7.4 and pH 8.4. The aqueous-phase reducing agents that offer speed
      advantages over sulfite alone include dithionite, thiosulfate, and iodide
      mediated sulfite. Ascorbic acid was the most reactive of the sulfur-free agents
      but was found to be slow relative to sulfite. The potential biological oxygen
      demand might constrain the choice of aqueous reductants. Metallic iron is shown
      to reduce inorganic and organic chloramines effectively. The implications of
      these results for wastewater chlorine reduction and analysis are discussed.

PMID- 15159155
TI  - Anaerobic biodegradation of aircraft deicing fluid in UASB reactors.
AB  - A central composite design was employed to methodically investigate anaerobic
      treatment of aircraft deicing fluid (ADF) in bench-scale Upflow Anaerobic Sludge
      Blanket (UASB) reactors. A total of 23 runs at 17 different operating conditions
      (0.8% 1.6% ADF (6000-12,000mg/L COD), 12-56h HRT, and 18-36gVSS/L) were conducted
      in continuous mode. The development of four empirical models describing process
      responses (i.e. COD removal efficiency, biomass-specific acetoclastic activity,
      methane production rate, and methane production potential) as functions of ADF
      concentration, hydraulic retention time, and biomass concentration is presented.
      Model verification indicated that predicted responses (COD removal efficiencies,
      biomass-specific acetoclastic activity, and methane production rates and
      potential) were in good agreement with experimental results. Biomass-specific
      acetoclastic activity was improved two-fold from 0.23gCOD/gVSS/d for inoculum to
      a maximum of 0.55gCOD/gVSS/d during ADF treatment in UASB reactors. For the
      design window, COD removal efficiencies were higher than 90%. The predicted
      methane production potentials were close to theoretical values, and methane
      production rates increased as the organic loading rate is increased. ADF toxicity
      effects were evident for 1.6% ADF at medium organic loadings (SOLR above
      0.5gCOD/gVSS/d). In contrast, good reactor stability and excellent COD removal
      efficiencies were achieved at 1.2% ADF for reactor loadings approaching that of
      highly loaded systems (0.73gCOD/gVSS/d).

PMID- 15159156
TI  - The use of isotopic and lipid analysis techniques linking toluene degradation to
      specific microorganisms: applications and limitations.
AB  - Phospholipid fatty acid (PLFA) analysis combined with (13)C-labeled tracers has
      been used recently as an environmental forensics tool to demonstrate microbial
      degradation of pollutants. This study investigated the effectiveness and
      limitations of this approach, applied to the biodegradation of toluene by five
      reference strains that express different aerobic toluene degradation pathways:
      Pseudomonas putida mt-2, P. putida F1, Burkholderia cepacia G4, B. pickettii
      PKO1, and P. mendocina KR1. The five strains were grown on mineral salts base
      medium amended with either 10 mM natural or [(13)C-ring]-labeled toluene. PLFA
      analysis showed that all five strains incorporated the toluene carbon into
      membrane fatty acids, as demonstrated by increases in the mass of fatty acids and
      their mass-spectrometry fragments for cells grown on (13)C-labeled toluene.
      Because of its ubiquitous presence and high abundance in bacteria, C16:0 fatty
      acid might be a useful biomarker for tracking contaminant degradation and (13)C
      flow. On the other hand, the (13)C-label (which was supplied at relatively high
      concentrations) generally exerted an inhibitory effect on fatty acid
      biosynthesis. Differences in fatty acid concentrations between cells grown on
      natural versus (13)C-labeled toluene would affect the interpretation of lipid
      profiles for microbial community analysis as indicated by principal component
      analysis of fatty acids. Therefore, caution should be exercised in linking lipid
      data with microbial population shifts in biodegradation experiments with (13)C
      labeled tracers.

PMID- 15159157
TI  - The effects of micro-aeration on the phylogenetic diversity of microorganisms in
      a thermophilic anaerobic municipal solid-waste digester.
AB  - We demonstrated previously that micro-aeration allows construction of an
      effective thermophilic methane-fermentation system for treatment of municipal
      solid waste (MSW) without production of H(2)S. In the present study, we compared
      the microbial communities in a thermophilic MSW digester without aeration and
      with micro-aeration by fluorescence in situ hybridization (FISH), denaturing
      gradient gel electrophoresis (DGGE), phylogenetic analysis of libraries of 16S
      rRNA gene clones and quantitative real-time PCR. Moreover, we studied the
      activity of sulfate-reducing bacteria (SRB) by analysis of the transcription of
      the gene for dissimilatory sulfite reductase (dsr). Experiments using FISH
      revealed that microorganisms belonging to the domain Bacteria dominated in the
      digester both without aeration and with micro-aeration. Phylogenetic analysis
      based on 16S rRNA gene and analysis of bacteria by DGGE did not reveal any
      obvious difference within the microbial communities under the two aeration
      conditions, and bacteria affiliated with the phylum Firmicutes were dominant. In
      Archaea, the population of Methanosarcina decreased while the population of
      Methanoculleus increased as a result of micro-aerations as revealed by the
      analysis of 16S rRNA gene clones and quantitative real-time PCR. Reverse
      transcription and PCR (RT-PCR) demonstrated the transcription of dsrA not only in
      the absence of aeration but also in the presence of micro-aeration, even under
      conditions where no H(2)S was detected in the biogas. In conclusion, micro
      aeration has no obvious effects on the phylogenetic diversity of microorganisms.
      Furthermore, the activity of SRBs in the digester was not repressed even though
      the concentration of H(2)S in the biogas was very low under the micro-aeration
      conditions.

PMID- 15159158
TI  - Combination of ferric and MIEX for the treatment of a humic rich water.
AB  - Seasonal periods of high rainfall have been shown to cause elevated natural
      organic matter (NOM) loadings at treatment works. These high levels lead to
      difficulties in removing sufficient NOM to meet trihalomethane (THM) standards,
      and hence better alternative treatments are required. Here the removal of NOM was
      investigated by a new ion exchange process (MIEX) using both bulk and
      fractionated NOM. Initial results showed that in excess of 80% of the raw water
      dissolved organic carbon (DOC) and greater than 85% of the UV absorbance from the
      bulk raw water could be removed by the use of MIEX alone. It was also seen that
      the removal of the more recalcitrant isolated fractions was increased. When MIEX
      was combined with a significantly reduced dose of coagulant a slight improvement
      on the overall DOC and UV removals was observed, however a significant decrease
      in the amount of THM formation potential (THMFP) in the final water was seen.
      This combined with the reduction in coagulant would imply a more efficient
      process during the times when the water becomes increasingly difficult to treat.

PMID- 15159159
TI  - Adsorption kinetics of polyethylene glycol from aqueous solution onto activated
      carbon.
AB  - The adsorption equilibrium and kinetics of polyethylene glycol (PEG) in three
      aqueous systems were examined in this study. Langmuir isotherm was used to
      satisfactorily predict the adsorption capacity of PEG on activated carbon F-400
      and applied to the investigation of adsorption kinetics. The surface diffusion,
      pore diffusion, and branched pore kinetics models successfully described the
      adsorption behavior of PEG on F-400 in the completely stirred tank reactor. The
      pore diffusion coefficients obtained from the pore diffusion model were compared
      with those computed by the experimental data of the short fixed-bed reactor
      combined with the assumption of non-hindered pore diffusion. In addition, the
      effects of initial concentrations of PEG and the relative importance of external
      and internal mass transfers for the adsorption were also taken into account and
      discussed in this study.

PMID- 15159160
TI  - Dynamics of nematodes in a high organic loading rotating biological contactors.
AB  - Nematode diversity and dynamics of a full-scale rotating biological contactor
      plant (RBC) has been studied. Analysis of biofilm composition showed a well
      established zoning of microfauna among the three RBC sections analysed. Nematodes
      appeared to be the dominant group within the larger microfauna populations with
      average abundances between 200 and 300ind/mg or 8000 and 17000ind/cm(2). The most
      abundant nematode species were Diplogasteritus nudicapitatus and Paroigolaimella
      coprophages and, to a lesser extent, Paroigolaimella bernensis and Steinernema
      intermedia. The relationship between nematodes and filamentous bacteria
      (specifically the genus Beggiatoa) was the most significant biotic relationship
      found, and to a lesser extent, nematodes with ciliates. The relationship between
      the abundance of nematode species and the physical-chemical variables suggests
      that nematodes may be good indicators of low pollutant load levels in the entry
      of the RBC system. Finally, the results indicate that nematodes may have a
      relevant role for a good biofilm development.

PMID- 15159161
TI  - Kinetics and mechanisms of DMSO (dimethylsulfoxide) degradation by UV/H(2)O(2)
      process.
AB  - The objective of this study was to elucidate the degradation pathways of
      dimethylsulfoxide (DMSO) during its mineralization caused by UV/H(2)O(2)
      treatment. In order to accomplish this, we measured the concentration time
      profiles of DMSO and its degradation intermediates during the UV/H(2)O(2)
      treatment. In addition, we proposed a kinetic model that could account for the
      degradation pathways of DMSO during its UV/H(2)O(2) treatment. The results show
      that the degradation of DMSO by the UV/H(2)O(2) treatment can be classified into
      two major pathways, and this is supported by both the analysis of the
      intermediates and total organic carbon (TOC) measurements. Firstly, DMSO was
      degraded into sulfate (SO(4)(2-)) through the formation of methansulfinate
      (CH(3)SO(2)(-)) and methansulfonate (CH(3)SO(3)(-)) as sulfur-containing
      intermediates. One of the two carbon constituents of DMSO was highly resistant to
      mineralization, due to the formation of methansulfonate, which reacted very
      slowly with (.-)OH k = 0.8 x 10(7) M(-1)s(-1)). Secondly, the other carbon
      constituent of DMSO was relatively easily mineralized through the formation of
      formaldehyde (HCHO) and formate (HCO(2)(-)) as non-sulfur-containing
      intermediates. The kinetic model proposed in this study for the degradation of
      DMSO by (.-)OH in the UV/H(2)O(2) process was able to successfully predict the
      patterns of concentration time-profiles of all components during the UV/H(2)O(2)
      treatment of DMSO.

PMID- 15159162
TI  - The occurrence of campylobacters in water sources in South Africa.
AB  - Campylobacter spp., mainly C. jejuni and C. coli, are recognized as significant
      human bacterial pathogens, being responsible for increasing numbers of
      gastroenteritis cases worldwide. Several reports have indicated that
      environmental waters are potential reservoirs and transmitting vehicles for these
      bacteria. The purpose of this study was thus to examine the occurrence of
      campylobacters in drinking and environmental water sources of South Africa, a
      country with a warmer climate and higher microbial pollution levels than those
      previously addressed in the Northern Hemisphere where similar investigations have
      been undertaken. Various types of water samples (five drinking water, four ground
      water, 11 surface water and four raw sewage) were collected from different parts
      of South Africa. Detection was by enrichment in Bolton broth prior to plating on
      both selective mCCDA or through a 0.6microm membrane filter on non-selective
      blood agar isolation media. Out of 100 initially selected Campylobacter-like
      isolates, only 22 did not grow aerobically and were subsequently identified as
      Campylobacter spp. by biochemical tests. However, the results obtained by 16S
      rRNA sequence analysis indicated that only three of these strains (13.6%) were
      Campylobacter jejuni and the remaining 19 strains were identified as Arcobacter
      butzleri. The spread of Arcobacter via water warrants further investigation,
      especially in view of the higher levels of detection and pathogenic nature of
      these bacteria.

PMID- 15159163
TI  - A study on the relationship between biodegradability enhancement and oxidation of
      1,4-dioxane using ozone and hydrogen peroxide.
AB  - Advanced oxidation involving O(3)/H(2)O(2) was used to eliminate 1,4-dioxane and
      to enhance the biodegradability of dioxane-contaminated water. Oxidation
      experiments were carried out in a bubble column reactor operating in fed-batch.
      The rate of dioxane removal and enhancement in biodegradability was investigated
      at hydrogen peroxide to ozone ratios between 0 and 0.6mol:mol and pH between 5
      and 11. A theoretical model was also applied to predict the experimental data and
      to investigate the effects of dioxane concentration, pH, and H(2)O(2)
      concentration. The model predictions fit the experimental data well and there was
      a linear correlation between dioxane oxidation and BOD enhancement. At low
      dioxane concentrations, the oxidation rate was first order and it gradually
      approached zero order with increasing dioxane concentration. Also, the
      biodegradability of the solution increased with pH up to about 9 and it stayed
      constant with further pH increase. Hydrogen peroxide initially enhanced dioxane
      removal and biodegradability enhancement of the solution. However, at
      H(2)O(2):O(3) ratios greater than about 0.4-0.45mol:mol, i.e. about 2.90mM for
      H(2)O(2) concentration, H(2)O(2) had negative impacts and resulted in reduced
      dioxane removal and biodegradability increase.

PMID- 15159164
TI  - Fluorescence of leachates from three contrasting landfills.
AB  - Landfill leachates are composed of a complex mixture of degradation products
      including dissolved organic matter, which includes a wide range of potentially
      fluorescent organic molecules and compounds. Here we investigate the excitation
      emission matrix fluorescence of landfill leachates from three contrasting
      landfill sites. Landfill fluorescence properties are all characterized by intense
      fluorescence at lambda(ex) =220-230nm, and lambda(em) =340-370nm which we suggest
      derives from fluorescent components of the Xenobiotic Organic Matter fraction
      such as naphthalene, as well as at lambda(ex) =320-360nm, and lambda(em) =400
      470nm from a higher molecular weight fulvic-like fraction. Landfill leachates are
      characterized by intense fluorescence, with approximately 10(2) intensity units
      of fluorescence at lambda(ex)=220-230nm, and lambda(em)=340-370nmmg(-1) of total
      organic carbon, demonstrating leachate detection limits of <0.1mgl(-1) total
      organic carbon. We demonstrate that for all landfill sites, leachate fluorescence
      intensity has a strong correlation with ground water quality determinants
      ammonia, total organic carbon and biochemical oxygen demand. We investigate both
      within-site and between-site leachate fluorescence properties, and demonstrate
      that although there is significant within-site variability, leachates from all 3
      sites can be statistically discriminated using just fluorescence properties (65%
      success rate) or with a combination of fluorescence and basic geochemical
      parameters (85%). Our findings suggest that fluorescence can be used as a rapid
      and sensitive tracer of leachate contamination of ground water, as well as help
      discriminate, together with geochemical determinants, leachates from different
      landfill sources.

PMID- 15159167
TI  - Motivation concepts in behavioral neuroscience.
AB  - Concepts of motivation are vital to progress in behavioral neuroscience.
      Motivational concepts help us to understand what limbic brain systems are chiefly
      evolved to do, i.e., to mediate psychological processes that guide real behavior.
      This article evaluates some major motivation concepts that have historic
      importance or have influenced the interpretation of behavioral neuroscience
      research. These concepts include homeostasis, setpoints and settling points,
      intervening variables, hydraulic drives, drive reduction, appetitive and
      consummatory behavior, opponent processes, hedonic reactions, incentive
      motivation, drive centers, dedicated drive neurons (and drive neuropeptides and
      receptors), neural hierarchies, and new concepts from affective neuroscience such
      as allostasis, cognitive incentives, and reward 'liking' versus 'wanting'.

PMID- 15159165
TI  - Rapid enumeration of virus-like particles in drinking water samples using SYBR
      green I-staining.
AB  - We studied the suitability of SYBR green I-staining for determining total counts
      of virus-like particles and bacteria in drinking water. Low background
      fluorescence and lack of unspecific staining made drinking water samples an
      excellent matrix for SYBR green I-staining. Direct microscopic count method is a
      rapid and economical tool for assessing the total number of virus-like particles
      in aquatic samples, compared to culture-dependent or molecular biology methods.
      We applied this method to show the efficiency of a large-scale drinking water
      purification process in the removal of virus-like particles and bacteria from
      lake water.

PMID- 15159168
TI  - Anabolic neuropeptides.
AB  - The hypothalamus and other brain regions that control energy homeostasis contain
      neuronal populations that produce specific neuropeptides which have experimental
      effects on feeding behavior and body weight. Here, we describe examples of
      neuropeptides that exert 'anabolic' effects, notably stimulation of feeding and
      increased body weight. Neuropeptide Y (NPY) neurons in the hypothalamic arcuate
      nucleus (ARC) are inhibited by leptin and insulin, and thus are stimulated in
      states of energy deficit and fat loss, e.g., underfeeding. NPY neuronal
      overactivity contributes to enhanced hunger and food-seeking activity under these
      conditions. The lateral hypothalamic area (LHA) contains specific neuronal
      populations that affect feeding in different ways. Neurons expressing the
      appetite-stimulating peptide orexin A are stimulated by starvation (but not food
      restriction) and by hypoglycemia, but only if food is withheld. Orexin neurons
      are apparently activated by low glucose but are promptly inhibited by visceral
      feeding signals, probably mediated via vagal sensory pathway and the nucleus of
      the solitary tract (NTS); a short-term role in initiating feeding seems most
      likely. Other LHA neurons express melanin-concentrating hormone (MCH), which
      transiently increases food intake when injected centrally. MCH neurons may be
      regulated by leptin, insulin and glucose. Glucose-sensing neurons in the
      hypothalamus and elsewhere are sensitive to other cues of nutritional state,
      including visceral satiety signals (transmitted via the vagus) and orexin A.
      Thus, long- and short-term humoral and neural signals interact with each other to
      meet diverse nutritional needs, and anabolic neuropeptides are important in the
      overall integration of energy homeostasis. Clarifying the underlying mechanisms
      will be essential to understanding normal energy balance and the pathogenesis and
      treatment of disorders, such as obesity and cachexia.

PMID- 15159169
TI  - Leptin signaling.
AB  - The discovery of leptin was a major breakthrough in our understanding of the role
      of adipose tissue as a storage and secretory organ. Leptin was initially thought
      to act mainly to prevent obesity; however, studies have demonstrated profound
      effects of leptin in the response to fasting, regulation of neuroendocrine and
      immune systems, hematopoiesis, bone and brain development. This review will focus
      on the signaling pathways which mediate these diverse effects of leptin in the
      brain and other physiologic systems.

PMID- 15159170
TI  - Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse:
      physiological and molecular characteristics.
AB  - The development of the metabolic syndrome in an increasing percentage of the
      populations of Western societies, particularly in the United States, requires
      valid models for establishing basic biochemical changes and performing
      preclinical studies on potential drug targets. The C57BL/6J mouse has become an
      important model for understanding the interplay between genetic background and
      environmental challenges such as high-fat/high-calorie diets that predispose to
      the development of the metabolic syndrome. This review highlights metabolic and
      signal transduction features that are altered during the course of disease
      progression, many of which mirror the human situation.

PMID- 15159171
TI  - Gastrointestinal mechanisms of satiation for food.
AB  - Satiation for food comprises the physiological processes that result in the
      termination of eating. Satiation is evoked by physical and chemical qualities of
      ingested food, which trigger afferent signals to the brain from multiple sites in
      the GI tract, including the stomach, the proximal small intestine, the distal
      small intestine and the colon. The physiological nature of each signal's
      contribution to satiation and overall control of food intake is likely to vary,
      depending on the level of the GI tract from which the signal arises. This article
      is a critical, though non-exhaustive, review of our current understanding of the
      mechanisms and adaptive value of satiation signals from the stomach and
      intestine.

PMID- 15159172
TI  - Ingested fat and satiety.
AB  - Apolipoprotein A-IV (apo A-IV) is secreted by the intestine associated with
      chylomicron. Intestinal apo A-IV synthesis is stimulated by fat absorption,
      probably mediated by chylomicron formation. The stimulation of apo A-IV synthesis
      in the jejunum and ileum is attenuated by intravenous leptin infusion. Intestinal
      apo A-IV synthesis is also stimulated by a factor from the ileum, probably
      peptide tyrosine-tyrosine (PYY), which has been demonstrated to affect satiety.
      Apo A-IV has been proposed to physiologically control food intake, and this
      inhibitory effect is centrally mediated. Recently, apo A-IV was demonstrated in
      the hypothalamus. The hypothalamic apo A-IV level was reduced by food deprivation
      and restored by lipid feeding. Intracerebroventricular administration of apo A-IV
      antiserum stimulated feeding and decreased the hypothalamic apo A-IV mRNA level,
      implying that feeding is normally limited by endogenous apo A-IV. Central
      administration of neuropeptide Y (NPY) significantly increased hypothalamic apo A
      IV mRNA levels in a dose-dependent manner. The stimulation of intestinal
      synthesis and secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV
      is capable of short-term regulation of food intake. Evidence also suggests apo A
      IV's involvement in long-term regulation of food intake and bodyweight. The
      chronic ingestion of high fat blunts the intestinal apo A-IV response to lipid
      feeding and may therefore explain why chronic intake of high fat predisposes
      animals and humans to obesity.

PMID- 15159173
TI  - Energy balance and reproduction.
AB  - The physiological mechanisms that control energy balance are reciprocally linked
      to those that control reproduction, and together, these mechanisms optimize
      reproductive success under fluctuating metabolic conditions. Thus, it is
      difficult to understand the physiology of energy balance without understanding
      its link to reproductive success. The metabolic sensory stimuli, hormonal
      mediators and modulators, and central neuropeptides that control reproduction
      also influence energy balance. In general, those that increase ingestive behavior
      inhibit reproductive processes, with a few exceptions. Reproductive processes,
      including the hypothalamic-pituitary-gonadal (HPG) system and the mechanisms that
      control sex behavior are most proximally sensitive to the availability of
      oxidizable metabolic fuels. The role of hormones, such as insulin and leptin, are
      not understood, but there are two possible ways they might control food intake
      and reproduction. They either mediate the effects of energy metabolism on
      reproduction or they modulate the availability of metabolic fuels in the brain or
      periphery. This review examines the neural pathways from fuel detectors to the
      central effector system emphasizing the following points: first, metabolic
      stimuli can directly influence the effector systems independently from the
      hormones that bind to these central effector systems. For example, in some cases,
      excess energy storage in adipose tissue causes deficits in the pool of oxidizable
      fuels available for the reproductive system. Thus, in such cases, reproduction is
      inhibited despite a high body fat content and high plasma concentrations of
      hormones that are thought to stimulate reproductive processes. The deficit in
      fuels creates a primary sensory stimulus that is inhibitory to the reproductive
      system, despite high concentrations of hormones, such as insulin and leptin.
      Second, hormones might influence the central effector systems [including
      gonadotropin-releasing hormone (GnRH) secretion and sex behavior] indirectly by
      modulating the metabolic stimulus. Third, the critical neural circuitry involves
      extrahypothalamic sites, such as the caudal brain stem, and projections from the
      brain stem to the forebrain. Catecholamines, neuropeptide Y (NPY) and
      corticotropin-releasing hormone (CRH) are probably involved. Fourth, the
      metabolic stimuli and chemical messengers affect the motivation to engage in
      ingestive and sex behaviors instead of, or in addition to, affecting the ability
      to perform these behaviors. Finally, it is important to study these metabolic
      events and chemical messengers in a wider variety of species under natural or
      seminatural circumstances.

PMID- 15159174
TI  - Salt appetite: a neurohormonal viewpoint.
AB  - Sodium is a key component of virtually every mammalian physiological function. As
      such, many animals have evolved specialized mechanisms for detecting and
      ameliorating deficits in body sodium, including the development of a robust salt
      appetite, where normally aversive concentrations of salt are readily consumed
      during periods of sodium deprivation. Here, we review research spanning more than
      half a century focusing on the condition and detection of sodium deprivation, the
      important and unique function of taste in sodium homeostasis, as well as the
      neurohormonal interactions leading to behaviors aimed at the reversal of sodium
      deficits. Based on the present literature, we propose a model for the interaction
      of forebrain and brainstem systems for the mediating circuitry giving rise to
      salt appetite and discuss the remarkable parallel between what is known about the
      neurohormonal interactions that regulate salt appetite and those involved in
      energy homeostasis.

PMID- 15159175
TI  - Opioids and alcoholism.
AB  - Although far from conclusive, evidence implicating the endogenous opioid system
      in the development and maintenance of alcoholism is growing. Currently available
      data suggest that ethanol increases opioid neurotransmission and that this
      activation is part of the mechanism responsible for its reinforcing effects.
      Findings from preclinical research indicate that ethanol consumption and ethanol
      induced dopamine (DA) release are both reduced by opioid antagonists. Individual
      differences in endogenous opioid activity have been linked to inherited risks for
      alcoholism in studies comparing ethanol-preferring and nonpreferring rats, as
      well as in studies using targeted gene mutation (knockout) strategies. To a large
      extent, findings from human studies have paralleled those from the preclinical
      work. Persons who differ in family history of alcoholism have been shown to also
      differ in basal beta-endorphin activity, beta-endorphin response to alcohol, and
      subjective and HPA axis hormonal response to opioid antagonists. Findings from
      clinical trials indicate that opioid antagonists may reduce ethanol consumption
      in alcoholics, particularly in persons who have resumed drinking. Nevertheless,
      many questions remain unanswered about the use of opioid antagonists in
      alcoholism treatment and about the exact role of the opioid system in ethanol
      preference and reward. The progression of knowledge in this field suggests that
      many of these questions are imminently answerable, as our ability to characterize
      relationships between opioid activity and human behavior continues to develop.
      This paper summarizes both the progress that has been made and the gaps that
      remain in our understanding of the interactions between the endogenous opioid
      system and risk for alcoholism.

PMID- 15159176
TI  - Eating disorders: clinical features and pathophysiology.
AB  - Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders of eating and weight
      related behavior that together afflict some 1-3% of women in the United States.
      One of the remarkable features about each of the eating disorders is how
      persistent the disordered eating behavior becomes once it has begun. Substantial
      psychological, social, and physiological disturbances are associated with eating
      disorders, and it has been very difficult to disentangle those factors that may
      result from the disturbed behavior from the factors that may have predisposed
      individuals to, or precipitated the development of, the disorder. This article
      will briefly review the definitions, phenomenology, and identified risk factors
      for development of each of the major eating disorders. Pathophysiology will be
      discussed, with a particular focus on candidate factors that might sustain
      disordered eating behavior, as informed by clinical and basic science research.
      Future research directions will be suggested.

PMID- 15159177
TI  - Nursing and men's health movement: considerations for the 21st century.
AB  - Men's health is a holistic, comprehensive approach that addresses the physical,
      mental, emotional, social, and spiritual life experiences and health needs of men
      throughout their lifespan. The men's health movement consists of various
      movements that are melding into a central focus on men's health and well being.
      Current health policy is attempting to establish an Office of Men's Health. A
      men's health nurse practitioner role is proposed for development.

PMID- 15159178
TI  - Men's health and psychosocial issues affecting men.
AB  - Contemporary scholars are calling on men to rethink "the male deal." As Samuels
      describes it, "In the male deal, the little boy, at around the age of 3 or 4.
      strikes a bargain with the social world in which he lives. If he will turn away
      from soft things, feminine things, maternal things...then the world will reward
      his gender certainty by giving him all the goodies in its possession." But the
      "deal" can have damaging effects, as shown in the studies reviewed in this
      article. Clinicians can help men to rethink the restrictions of the "male deal"
      so that they may experience the freedom of a wider emotional repertoire and move
      toward greater joy and wholeness.

PMID- 15159179
TI  - Male battering of intimate partners: theoretical underpinnings, intervention
      approaches, and implications.
AB  - Male battering of intimate partners is a serious men's health issue related to
      violence that calls for the profession of nursing to engage in practice,
      research, education, and policy initiatives. It inflicts damage and harm to
      society, and no one is insulated from the problem completely because of its
      social, health, and legal implications. Scholars and practitioners lack an
      adequate understanding of the confluence of myriad sociological, psychological,
      biological, and environmental risk factors in the developmental pathways to male
      battering. Prevention at the primary and secondary level of intervention is
      thwarted. Existing models of intervention have been useful in confronting the
      problem of male battering, but large-scale evaluations and clinical trials of
      intervention approaches are needed. Interventionists operate from varied
      theoretical perspectives, so that there is no general consensus on what
      constitutes best practices. Nursing, health-related, sociological, and criminal
      justice professionals have an excellent and timely opportunity to improve the
      health, safety, and well-being of individuals, families, and communities by
      addressing male battering in their scholarship and practice endeavors.

PMID- 15159180
TI  - Men's cardiovascular and pulmonary health.
AB  - Heart disease in men is declining steadily, but it remains the number one killer
      of men in the United States. CLRD, influenza/pneumonia, and lung cancer are three
      more causes of top 10 mortalities in men. Epidemiological and clinical studies
      conclude that CVD is largely preventable through lifestyle modification. CHD,
      COPD, occupational lung disease, and lung cancer are all preventable by primary
      prevention (ie, no cigarette smoking). All men should be counseled about the
      grave significance of heart and lung disease as a cause of illness and death, the
      importance of primary prevention, and the great variability in symptom
      presentation. Nurses are in the ideal position to educate patients, families, and
      colleagues about heart and lung disease.

PMID- 15159181
TI  - Changing men's involvement in reproductive health and family planning.
AB  - The shift in focus on men's reproductive health was influenced by the 1994 Cairo
      (ICPD) Action Plan to promote gender equality and equity, empower women, and
      improve family health in society. Changing and improving the way in which men are
      involved in reproductive health can only have a positive impact on women's,
      men's, and children's health. Educating and counseling men about contraceptive
      choices is essential if they are to be supportive of women's reproductive health.
      Research on new male contraceptive methods must continue if the bias of women
      shouldering the major responsibility for contraception is to be eliminated.

PMID- 15159182
TI  - Penile and testicular disorders.
AB  - Circumcision, priapism, phimosis, Peyronie's disease, orchitis, epididymitis, and
      testicular torsion are conditions of the male penis and testicles that warrant
      increased attention by health care providers in practice. Healthy outcomes for
      penile and testicular disorders can be achieved through education, enhanced
      screening, and adequate comprehensive treatment. Penile and testicle disorders
      provide researchers and clinicians with many opportunities for research and
      practice that can improve the condition of men's health.

PMID- 15159183
TI  - Cancers of the prostate, penis, and testicles: epidemiology, prevention, and
      treatment.
AB  - Cancer is a disease that most people fear. Nurses are required to provide
      information on how to avoid cancer, and, once the diagnosis is made, how to cope
      with it. Prevention and early detection of the cancers described in this article
      are in the very early stages of knowledge development, but general health
      promotion guidance can be offered on how to avoid most cancers (ie, no tobacco
      use, a high-fiber and low fat diet, exercise, and maintaining a normal weight).
      Nurses also can advise patients to be screened for colorectal cancer at the
      appropriate ages and time intervals and to be aware as new developments occur in
      the scientific base for screenings in the areas of prostate, penile, and
      testicular cancer. Finally, coping with these forms of cancer often requires the
      patient to make major lifestyle and psychological changes, especially if surgery
      in the genital area occurs. Decreased libido, incontinence, and impotence are
      major complications that can occur with these illnesses. The male cancers
      described vary tremendously in their prevalence, incidence, mortality, treatment,
      and survival rates. Within this group, there are remarkably positive outcomes and
      outcomes much in need of improvement. Penile and testicular cancers are the
      bright spots in this picture; both are uncommon, and both are eminently
      treatable. Prostate cancer, on the other hand, is quite common, difficult to
      screen, difficult to treat without major sexual problems, and yet receives
      relatively little funding from the NIH. Although as many men die from prostate
      cancer as women die from breast cancer, NIH funds breast cancer research at much
      higher levels than prostate cancer. According to the latest data available at the
      NIH Web site, during the 1990s, the amount of NIH funding varied from four times
      more for breast cancer (1993) to 2.9 times more in 1999. For fiscal year 2002,
      NIH is providing $522 million in funding for breast cancer and $278 million for
      prostate cancer. Private foundation funds for prostate cancer are much smaller
      than those available for breast cancer. Both types of cancer are extremely
      important to address, and both should receive adequate research attention. Nurses
      can advocate for more funding for prostate cancer, from basic science approaches
      to behavioral science strategies.

PMID- 15159184
TI  - Male sexuality in theory and practice.
AB  - Male sexuality is a complex phenomenon shaped by personal, cultural,and social
      factors. This article has argued that male sexual function is an important
      consideration in conditions such as prostate cancer. There are surely other
      conditions where it is understood even more poorly. Although theorists tend to
      explore male sexuality in relation to vague concepts such as power,
      phallocentrism, and aggression, sexuality becomes a personal reality in illness
      contexts. Using insights from a study into prostate cancer, it has been suggested
      that men assess embodied risks, such as impotence, in highly individual ways. The
      uncertainty that characterizes this cancer further compounds the difficulties
      involved, despite attempts of professionals to provide adequate levels of
      information and support. Researchers and practitioners alike should begin to
      question the gap between theoretical constructions of male sexuality and its
      reality in healthcare situations. More attention should be paid to understanding
      the importance of sexual function for men who are living with conditions such as
      prostate cancer. Those men who face up to the threat of such embodied changes,
      and who learn to cope with physical and emotional (and sexual) vulnerability, may
      learn to evaluate their lives in new ways. As Kenneth, one of the participants in
      this study said of his experience of cancer, "It just seems unnecessary for them
      to have to go through that to learn and understand themselves and be honest with
      themselves about what is really important."

PMID- 15159185
TI  - Sexually transmitted diseases in men.
AB  - Sexually transmitted diseases are the most common infectious diseases in the
      United States. Physicians, nurses, and other health care providers are
      uncomfortable discussing sexual issues with their clients. Therefore many health
      care needs are not addressed, and many opportunities for education aimed at
      preventing STDs are missed. In the periodic health history, the health care
      provider must elicit information about sexual practices (vaginal,oral, or anal
      intercourse), sexual orientation (heterosexual, homosexual, or bisexual), sexual
      risk behaviors (ie, unprotected intercourse with multiple partners),
      contraceptive use (particularly condoms), and prior STDs. Based on this
      information, the health care practitioner moves to more specific questions
      regarding sexual health. The health care practitioner asks about sores on the
      penis, dripping or discharge from the penis, staining of the underwear,
      testicular pain, and scrotal swelling. For the client who engages in oral sex,
      the health care practitioner asks about sore throat. For the client who engages
      in anal intercourse ask about diarrhea, rectal bleeding, anal itching, and pain.
      Probe the desire phase, the arousal phase (erection), and the ejaculation phase.
      Ask about the desire for fatherhood and concerns about fatherhood. An important
      part of health care is prevention. Culturally specific and sensitive information
      should be available for patients. Patient education should not consist of simply
      handing a brochure to a man. Using the brochure as a guide for including all the
      necessary information and ascertaining the man's understanding may be a very
      effective method of patient education. For men who are at increased risk for STDs
      or who present with symptoms of STDs, offering diagnostic testing is necessary.
      Men who have multiple sexual partners especially need diagnostic testing and
      prevention counseling. The CDC recommends annual HIV and hepatitis C testing for
      men who have sex with men and other men who have increased risk for contracting
      HIV. Another important consideration at the periodic screening examination is the
      vaccinations that are to be recommended. Men who have sex with men should receive
      hepatitis A and hepatitis B vaccine. Additionally, it is recommended that all
      adolescents should receive hepatitis B vaccine.

PMID- 15159186
TI  - Women's conditions occurring in men: breast cancer, osteoporosis, male menopause,
      and eating disorders.
AB  - Each of the four disorders discussed in this article emphasizes its significance
      in the morbidity and mortality of men. Recent research has improved the ability
      to identify many of the key risk factors that could predispose men to breast
      cancer, osteoporosis, male menopause, and eating disorders. There is a
      significant need for further research into each of these conditions, as most
      studies have been conducted on women. The myths that these disorders are just a
      feminist issue can be ignored no longer. Nurses are in a prime position to help
      men identify and analyze their risks and help them select appropriate prevention
      and screening strategies to improve their knowledge and quality of life.

PMID- 15159187
TI  - Occupational health injuries: a brief review of three disorders.
AB  - Carpal tunnel syndrome, NIHL, and work-related hernias are preventable
      occupational injuries that result in decreased productivity because of lost
      workdays. The treatment paradigm focuses almost exclusively on preventing further
      loss or injury through employee education. There is a dearth of studies related
      to NIHL and hernias. These areas should provide a fertile ground for nurse
      researchers who are interested in improving occupational health outcomes for the
      nation's work force by being part of an interdisciplinary team that investigates
      these areas of concern. The key is that prevention is cheaper than treatment for
      these injuries.

PMID- 15159188
TI  - Issues in gay men's health.
AB  - Health care for gay men is a complicated mix of physical, psychosocial,and
      cultural phenomena that needs further empirical study and research. Gay men's
      health issues are unique and need to be incorporated into clinical practice to
      provide comprehensive and culturally appropriate care to MSM.

PMID- 15159189
TI  - Healthy aging: health promotion and disease prevention.
AB  - Successful aging includes the ability to perform functional tasks. This ability
      to perform functional tasks, or functional ability, is influenced by
      musculoskeletal and cardiovascular functioning and the presence and severity of
      symptoms of chronic disease. Empirical evidence indicates that musculoskleletal
      and cardiovascular functioning and symptoms of chronic disease in later life are
      strongly related to lifestyle choices involving physical activity and nutritional
      intake. Previous researchers have demonstrated that increases in physical
      activity and appropriate changes in nutritional intake can be effective
      interventions to prevent and treat symptoms of chronic disease and improve
      musculoskeletal and cardiovascular functioning. As a result of this evidence,
      several organizations have developed physical activity and nutritional intake
      recommendations aimed at maintaining or increasing the functional ability of
      older adults. These physical activity recommendations include engaging in
      cardiorespiratory, flexibility, strength, and balance training 3 to 5 days per
      week. Broad nutritional recommendations for older adults include a low-fat, plant
      based diet including fruits, vegetables, whole grains, 8 glasses of water per
      day, and a vitamin and mineral supplement.

PMID- 15159191
TI  - Comprehension of idioms in adolescents with language-based learning disabilities
      compared to their typically developing peers.
AB  - Adolescents with language-based learning disabilities (LBLD) often interpret
      idioms literally. When idioms are provided in an enriched context, comprehension
      is compromised further because of the LBLD student's inability to assign multiple
      meanings to words, assemble and integrate information, and go beyond a local
      referent to derive a global, coherent meaning. This study tested the effects of
      context and familiarity on comprehension of 24 idioms in 22 adolescents with
      LBLD. The students completed the Idiom Comprehension Test (ICT) [Language,
      Speech, and Hearing Services in Schools 30 (1999) 141; LSHSS 34 (2003) 69] in one
      of two conditions: in a story or during a verification task. Within each
      condition were three familiarity levels: high, moderate, and low. The LBLD
      adolescents' data were then compared to previously collected data from 21 age-,
      gender-, and reading ability-matched typically developing (TD) peers. The
      relations between reading and language literacy and idiom comprehension were also
      examined in the LBLD adolescents. Results showed that: (a) the LBLD adolescents
      generally performed poorly relative to their TD counterparts; however, the groups
      performed comparably on the high and moderate familiarity idioms in the
      verification condition; (b) the LBLD adolescents performed significantly better
      in the verification condition than in the story condition; and (c) reading
      ability was associated with comprehension of the low familiarity idioms in the
      story condition only. Findings are discussed relative to implications for speech
      language pathologists (SLPs) and educators working with adolescents with LBLD.
      LEARNING OUTCOMES: As a result of this activity, the participant will be able to
      (1) describe the importance of metalinguistic maturity for comprehension of
      idioms and other figures of speech; (2) understand the roles of context and
      familiarity when assessing idiom comprehension in adolescents with LBLD; and (3)
      critically evaluate assessments of idiom comprehension and determine their
      appropriateness for use with adolescents with LBLD.

PMID- 15159192
TI  - Pediatricians' opinions about otitis media and speech-language-hearing
      development.
AB  - Twenty-five pediatricians responded to a confidential survey about their opinions
      on the relationship between otitis media and children's speech-language-hearing
      status. Results found that pediatricians did not necessarily agree that otitis
      media has an impact on speech-language-hearing development. Pediatricians
      reported that an early otitis media onset (birth to age 2) affects speech
      language development, but they also reported that parents and daycare
      environments could mitigate any otitis media effect. Pediatricians reported a
      possible otitis media impact on hearing status, but they did not necessarily
      agree that an otitis media history required referral for audiological testing.
      Clinical implications are discussed for collaboration among pediatricians, speech
      language pathologists, and audiologists. LEARNING OUTCOMES: (1) The reader will
      become familiar with pediatricians' opinions about the impact of otitis media on
      speech-language development. (2) The reader will become familiar with strategies
      to support interdisciplinary collaboration between pediatricians, speech-language
      pathologists, and audiologists.

PMID- 15159193
TI  - Stuttering and the basal ganglia circuits: a critical review of possible
      relations.
AB  - The possible relation between stuttering and the basal ganglia is discussed.
      Important clues to the pathophysiology of stuttering are given by conditions
      known to alleviate dysfluency, like the rhythm effect, chorus speech, and
      singing. Information regarding pharmacologic trials, lesion studies, brain
      imaging, genetics, and developmental changes of the nervous system is reviewed.
      The symptoms of stuttering are compared with basal ganglia motor disorders like
      Parkinson's disease and dystonia. It is proposed that the basal ganglia
      thalamocortical motor circuits through the putamen are likely to play a key role
      in stuttering. The core dysfunction in stuttering is suggested to be impaired
      ability of the basal ganglia to produce timing cues for the initiation of the
      next motor segment in speech. Similarities between stuttering and dystonia are
      indicated, and possible relations to the dopamine system are discussed, as well
      as the interaction between the cerebral cortex and the basal ganglia. Behavioral
      and pharmacologic information suggests the existence of subtypes of stuttering.
      LEARNING OUTCOMES: As a result of this activity, the reader will (1) become
      familiar with the research regarding the basal ganglia system relating to speech
      motor control; (2) become familiar with the research on stuttering with
      indications of basal ganglia involvement; and (3) be able to discuss basal
      ganglia mechanisms with relevance for theory of stuttering.

PMID- 15159194
TI  - Phonation offset in tracheoesophageal speech.
AB  - Tracheoesophageal (TE) speakers often have difficulty producing the voiced
      voiceless distinction. Phonation offset (POff) as a TE speaker transitions from a
      vowel to a stop consonant may be altered, possibly contributing to listener
      misperceptions. The purposes of this study were to: (1) compare the duration of
      POff in TE versus laryngeal speakers, and (2) compare POff between TE productions
      that were accurately versus inaccurately perceived. Phonation offset and offset
      duration as a proportion of the stop gap (%POff) were greater for the TE versus
      the laryngeal samples. There was no difference in POff or %POff when comparing
      accurately to inaccurately perceived TE samples. Tracheoesophageal speakers may
      have less ability to halt neoglottal vibration compared to laryngeal speakers'
      ability to stop glottal vibration. Comparable POff for accurately and
      inaccurately perceived TE samples suggests that POff may not be a particularly
      salient acoustic feature to the voicing distinction, at least for stop
      consonants. LEARNING OUTCOMES: (1) As a result of this activity, participants
      will be able to describe what phonation offset is relative to the voicing
      distinction. (2) As a result of this activity, participants will be able to
      describe phonation offset in tracheoesophageal speakers relative to laryngeal
      speakers. (3) As a result of this activity, participants will be able to describe
      whether phonation offset in tracheoesophageal speech has perceptual saliency for
      listeners.

PMID- 15159195
TI  - Information technology and road transport industry: how does IT affect the lorry
      driver?
AB  - A quasi-experimental design was used to study the effect of on board computer
      systems (OBC-systems) on the Dutch lorry drivers' psychosocial work environment
      (i.e., control and demands) and coinciding mental health (i.e., need for recovery
      after work) and job attitudes (i.e., organisational commitment). The intervention
      group (n = 26) started working with an OBC-system between 1998 and 2000 and was
      compared with two matched reference groups (n = 26 in both groups). All
      participants were from a cohort of 650 drivers who participated in a prospective
      study on occupational stress and health. All outcome variables were quantified by
      standardised and validated questionnaires. Results showed that the application of
      OBC-systems negatively affected the drivers' job control and organisational
      commitment. However, OBC-systems did not influence the drivers' psychological job
      demands and need for recovery after work. Accordingly, it is concluded that the
      application of OBC-systems negatively affects the lorry driver's psychosocial
      work environment and job attitudes.

PMID- 15159196
TI  - Validation of an instrument for patient handling assessment.
AB  - Nursing personnel are at high risk from work-related musculoskeletal disorders,
      especially back symptoms. Handling patients has been established as one of the
      factors playing an important role in the etiology of occupational low back pain.
      The aim of this study was to develop an instrument for patient handling
      assessment and to determine its validity and reliability. Instrument validity was
      established based on content and construct validity. Reliability was estimated
      through homogeneity, stability (test-retest) and equivalence (interrater) tests.
      Reliability estimated by internal consistency reached a Cronbach's Alpha
      coefficient of 0.81. Pearson's correlation coefficient for test-retest
      reliability was r = 0.92. There was an excellent agreement between observers,
      according to the k values (Kappa = 0.92). Interobserver (interrater) reliability
      was assessed by Pearson's correlation coefficient, reaching an r value of 0.84.
      The agreement between both observers was also fairly good (Kappa = 0.84). The
      results of the current study show that the instrument seems to be reliable and
      valid for patient handling assessment.

PMID- 15159197
TI  - Effects of load carriage, load position, and walking speed on energy cost of
      walking.
AB  - PURPOSE: The purpose of this study was to examine the effects of load, load
      position, and walking speed on the energy cost of walking per unit distance (Cw:
      ml/kg/m). METHODS: Eight young male subjects walked on a treadmill at various
      speeds with and without load in the hands, on the back, and on the legs. The Cw
      values were determined from the ratio of 2-min steady-state oxygen consumption
      (Vo2) above resting value (net Vo2) to the walking speed (v): Cw = net Vo2/v.
      RESULTS: An energy-saving phenomenon was observed when the load was carried on
      the back at slower speeds. This phenomenon diminished at faster speeds,
      particularly when walking faster than 90 m/min. It was also observed when the
      load was carried in the hands at slower speeds. CONCLUSIONS: These findings
      partly supported our hypothesis that an energy-saving phenomenon would be
      observed due to an interaction between rotative torque around the center of body
      mass and excessive burden on the lower muscles as a function of speed.

PMID- 15159198
TI  - The effect of forearm support on musculoskeletal discomfort during call centre
      work.
AB  - Using a computer keyboard with the forearms unsupported has been proposed as a
      causal factor for neck/shoulder and arm/hand diagnoses. Recent laboratory and
      field studies have demonstrated that forearm support might be preferable to
      working in the traditional "floating" posture. The aim of this study was to
      determine whether providing forearm support when using a normal computer
      workstation would decrease musculoskeletal discomfort in intensive computer users
      in a call centre. A randomised controlled study (n = 59), of 6 weeks duration was
      conducted. Thirty participants (Group 1) were allocated to forearm support using
      the desk surface with the remainder (Group 2) acting as a control group. At 6
      weeks, the control group was also set up with forearm support. Both groups were
      then monitored for another 6 weeks. Questionnaires were used at 1, 6 and 12 weeks
      to obtain information about discomfort, workstation setup, working posture and
      comfort. Nine participants (Group 1 n = 6, Group 2 n = 3) withdrew within a week
      of commencing forearm support either due to discomfort or difficulty in
      maintaining the posture. At 6 weeks, the group using forearm support generated
      significantly fewer reports of discomfort in the neck and back, although the
      difference between the groups was not statistically significant. At 12 weeks,
      there were fewer reports of neck, back and wrist discomfort when preintervention
      discomfort was compared with post intervention discomfort. These findings
      indicate that for the majority of users, forearm support may be preferable to the
      "floating" posture implicit in current guidelines for computer workstation setup.

PMID- 15159199
TI  - Processes, barriers, and outcomes described by ergonomics consultants in
      preventing work-related musculoskeletal disorders.
AB  - Despite the importance of reducing work-related musculoskeletal disorders, there
      appears to have been little evaluation of routine ergonomics consultancy
      interventions aimed at reducing risks leading to these conditions. In many
      instances, the effectiveness of advice depends on organisations accepting and
      implementing measures recommended, involving changes of both individual and
      collective behaviour. Behaviour change theory, developed elsewhere, suggests that
      if change is to take place, recipients need to hold positive attitudes and
      beliefs relating to the desirable behaviour. To investigate the extent to which
      this is accommodated by current ergonomics consultancy practices, 14 ergonomics
      consultants were interviewed to explore the consultancy process from which
      recommendations are developed, exploring the factors that are assessed by
      consultants, perceived barriers to promoting change, and the extent to which
      evaluation of outcomes takes place. Consultants' recommendations generally
      focused on physical aspects of the work environment and did not take explicit
      account of employees' knowledge or attitudes. Little evaluation of outcomes was
      conducted by the consultants interviewed. Implications of these findings for
      improving the efficacy of interventions to reduce work-related musculoskeletal
      disorders within organisations are discussed.

PMID- 15159200
TI  - Measurement protocol of women's nude breasts using a 3D scanning technique.
AB  - It has been difficult to obtain accurate surface data for women's breasts, since
      the borderline of the breast is ambiguous at the skin surface. In this paper, we
      scanned 37 women's nude breasts using 3D phase shifting moire and explored a
      measurement protocol to get a reliable boundary of the breast and thereby
      provided new shape parameters for breasts. The folding line method was useful for
      finding a continuous and natural boundary for the breasts, so that the breasts
      base and volume could be measured more accurately. The global average radius of
      the curvature of the bottom breast line was suggested as a useful shape parameter
      for the design of a comfortable and form-fitting brassiere, especially for those
      who have a skewed bottom breast curve. It is also expected that data on breast
      volume based on natural anatomy would be a useful reference for surgical
      operation on the breast.

PMID- 15159201
TI  - Universal product design involving elderly users: a participatory design model.
AB  - Recent studies have shown that people prefer to age in their familiar
      environments, thus guiding designers to provide a safe and functionally
      appropriate environment for ageing people, regardless of their physical
      conditions or limitations. Therefore, a participatory design model is proposed
      where human beings can improve their quality of life by promoting independence,
      as well as safety, useability and attractiveness of the residence. Brainstorming,
      scenario building, unstructured interviews, sketching and videotaping are used as
      techniques in the participatory design sessions. Quality deployment matrices are
      employed to find the relationships between the elderly user's requirements and
      design specifications. A case study was devised to apply and test the conceptual
      model phase of the proposed model.

PMID- 15159202
TI  - Determining the effects of eyewear fogging on visual task performance.
AB  - The effect of fog on eyewear was evaluated by having individuals perform a target
      detection task in environments that typically cause eyewear to fog while wearing
      either eyewear that had been treated with anti-fog coating, eyewear not treated,
      or no eyewear. Detection was higher with eyewear that had been treated with anti
      fog coating compared to uncoated lenses and no difference was observed between
      wearing coated eyewear and wearing no eyewear. The study concluded that fogging
      of lenses has a significant effect on visual detection and the use of anti-fog
      coating is relatively effective. However, in environments where prolonged fogging
      occurs water droplets form on anti-fog coated lenses which disrupts visual
      performance in a manner similar to the fog it is trying to prevent. It is
      recommended that anti-fog coating be considered when purchasing protective
      eyewear, and a bench test be developed to assess the coatings applied to eyewear.

PMID- 15159203
TI  - Microgravity simulation: physical and psychological workload evaluation tests in
      an underwater environment.
AB  - As weightlessness is not completely reproducible on Earth, usability evaluation
      of space systems is often simulated through tests in an aquatic environment. A
      Neutral Buoyancy Facility test programme was organized in a special pool to
      simulate Extra-Vehicular Activities on the Columbus module of the future
      International Space Station with the aim of assessing various aspects of crew
      interface design. This study was designed to evaluate workload using visibility,
      accessibility and operability tests. Diving workload was determined through basic
      physiological measurements, such as pulmonary ventilation and heart rate during
      underwater operations. As anxiety can influence physiological processes, and
      consequently also the workload evaluation determined through these parameters, we
      developed an evaluation methodology to investigate the anxiety level based on a
      specific questionnaire submitted to all subjects before and after the dives.
      Heart rate increased in underwater work to a value approximately 50% larger than
      the value obtained in the resting condition while sitting outside the pool. This
      increase in heart rate was accompanied by an increase in pulmonary ventilation of
      200% larger than the value recorded in the rest condition while sitting outside
      the water. The extent of these increases was notable in all the test subjects,
      who varied in age and stature. Recorded values of workload, heart rate and
      pulmonary ventilation were evaluated on the basis of Christensen's
      (Arbeitsphysiol. 14 (1950) 251) and Wells' (J. Appl. Physiol. 10 (1957) 51)
      classifications. Through this analysis it was possible to determine that the
      workload, indicated by performance on our neutral buoyancy tests, corresponds to
      moderate physiological work. For test subjects, anxiety related to underwater
      performance was light. Among the causes of anxiety all the subjects indicated the
      lack of confidence with neutral buoyancy tests and a feeling of lack of safety,
      typical of aquatic environments. We can conclude that context did not produce
      considerable psychological effects, and consequently that the psychological load
      did not influence heart rate and pulmonary ventilation values that can therefore
      be directly related to task workload.

PMID- 15159204
TI  - Development and evaluation of an affordable lift device to reduce musculo
      skeletal injuries among home support workers.
AB  - Home support workers (HSWs) work in clients' homes assisting with rehabilitation
      and activities of daily living. Like all health-care professionals, HSWs are at
      an increased risk for developing back injuries. Lift devices have been shown to
      reduce injuries to the worker. Presently, there are few lifting devices for home
      use that cost under $4000 CDN. Our study involved designing a safe and affordable
      lift device (retail cost under $2000 CDN) to be used by HSWs in the home and
      evaluating it in a typical bathroom. Thirty-eight HSWs and three seniors
      evaluated the BCIT lift, a commercially available lift (BHM Medical Inc.) and the
      manual method of transfer and lift. Results indicated that the BCIT lift was an
      improvement over the manual method of transferring, and approximated the more
      expensive, automatic lift in terms of perceived exertion, ease of use and safety.
      Feedback provided to the researchers has been incorporated into a new,
      ergonomically sound and marketable lift device.

PMID- 15159205
TI  - Assessing floor slipperiness in fast-food restaurants in Taiwan using objective
      and subjective measures.
AB  - Slips and falls are major problems in occupational injuries in which floor
      slipperiness is a critical issue. Most of the studies on slipperiness assessments
      were conducted in laboratories. Field assessments are rarely reported in the
      literature. This study investigated floor slipperiness in seven kitchen areas of
      10 western-style fast-food restaurants in Taiwan using both objective and
      subjective measurements which were conducted by friction measurements and by
      employees' ratings of floor slipperiness, respectively. The friction measurement
      results showed that the sink area had the lowest average friction in the
      kitchens. Employees, however, rated both the sink and back vat (chicken fry)
      areas as the most slippery areas. The Pearson's and Spearman's correlation
      coefficients between the averaged friction coefficients and subjective ratings
      for all 70 evaluated areas across all 10 restaurants were 0.49 and 0.45,
      respectively, with p < 0.0001 for both. The results indicate that average
      friction coefficient and perception are in fair agreement, suggesting that both
      might be reasonably good indicators of slipperiness.

PMID- 15159206
TI  - Using a customized DNA microarray for expression profiling of the estrogen
      responsive genes to evaluate estrogen activity among natural estrogens and
      industrial chemicals.
AB  - We developed a DNA microarray to evaluate the estrogen activity of natural
      estrogens and industrial chemicals. Using MCF-7 cells, we conducted a
      comprehensive analysis of estrogen-responsive genes among approximately 20,000
      human genes. On the basis of reproducible and reliable responses of the genes to
      estrogen, we selected 172 genes to be used for developing a customized DNA
      microarray. Using this DNA microarray, we examined estrogen activity among
      natural estrogens (17beta-estradiol, estriol, estrone, genistein), industrial
      chemicals (diethylstilbestrol, bisphenol A, nonylphenol, methoxychlor), and
      dioxin. We obtained results identical to those for other bioassays that are used
      for detecting estrogen activity. On the basis of statistical correlations
      analysis, these bioassays have shown more sensitivity for dioxin and
      methoxychlor.

PMID- 15159207
TI  - Toxicogenomics of subchronic hexachlorobenzene exposure in Brown Norway rats.
AB  - Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic
      effects in man and rat. Reported adverse effects are hepatic porphyria,
      neurotoxicity, and adverse effects on the reproductive and immune system. To
      obtain more insight into HCB-induced mechanisms of toxicity, we studied gene
      expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were fed
      a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric lymph nodes
      (MLN), thymus, blood, liver, and kidney were collected and analyzed using the
      Affymetrix rat RGU-34A GeneChip microarray. Most significant (p < 0.001) changes,
      compared to the control group, occurred in spleen, followed by liver, kidney,
      blood, and MLN, but only a few genes were affected in thymus. This was to be
      expected, as the thymus is not a target organ of HCB. Transcriptome profiles
      confirmed known effects of HCB such as stimulatory effects on the immune system
      and induction of enzymes involved in drug metabolism, porphyria, and the
      reproductive system. In line with previous histopathological findings were
      increased transcript levels of markers for granulocytes and macrophages. New
      findings include the upregulation of genes encoding proinflammatory cytokines,
      antioxidants, acute phase proteins, mast cell markers, complements, chemokines,
      and cell adhesion molecules. Generally, gene expression data provide evidence
      that HCB induces a systemic inflammatory response, accompanied by oxidative
      stress and an acute phase response. In conclusion, this study confirms previously
      observed (immuno)toxicological effects of HCB but also reveals several new and
      mechanistically relevant gene products. Thus, transcriptome profiles can be used
      as markers for several of the processes that occur after HCB exposure.

PMID- 15159208
TI  - Metal particulate matter components affect gene expression and beat frequency of
      neonatal rat ventricular myocytes.
AB  - Soluble particulate matter (PM) components (e.g., metals) have the potential to
      be absorbed into the bloodstream and transported to the heart where they might
      induce the expression of inflammatory cytokines and remodel electrical
      properties. We exposed cultured rat ventricular myocytes to similar
      concentrations of two metals [zinc (Zn) and vanadium (V)] found commonly in PM
      and measured changes in spontaneous beat rate. We found statistically significant
      reductions in spontaneous beat rate after both short-term (4-hr) and long-term
      (24-hr) exposures, with a more substantial effect seen with Zn. We also measured
      the expression of genes associated with inflammation and a number of sarcolemmal
      proteins associated with electrical impulse conduction. Exposure to Zn or V (6.25
      50 microM) for 6 hr produced significant increases in IL-6, IL-1 alpha, heat
      shock protein 70, and connexin 43 (Cx43). After 24 hr exposure, Zn induced
      significant changes in the gene expression of Kv4.2 and KvLQt (potassium channel
      proteins), the alpha 1 subunit of the L-type calcium channel, and Cx43, as well
      as IL-6 and IL-1 alpha. In contrast, V produced a greater effect on Cx43 and
      affected only one ion channel (KvLQT1). These results show that exposure of rat
      cardiac myocytes to noncytotoxic concentrations of Zn and V alter spontaneous
      beat rate as well as the expression of ion channels and sarcolemmal proteins
      relevant to electrical remodeling and slowing of spontaneous beat rate, with Zn
      producing a more profound effect. As such, these data suggest that the cardiac
      effects of PM are largely determined by the relative metal composition of
      particles.

PMID- 15159209
TI  - Inhibition of Ape1 nuclease activity by lead, iron, and cadmium.
AB  - Many environmental metals are co-carcinogens, eliciting their effects via
      inhibition of DNA repair. Apurinic/apyrimidinic (AP) endonuclease 1 (Ape1) is the
      major mammalian abasic endonuclease and initiates repair of this
      cytotoxic/mutagenic lesion by incising the DNA backbone via a Mg(2+)-dependent
      reaction. In this study we examined the effects of arsenite [As(III)], cadmium
      [Cd(II)], cobalt [Co(II)], iron [Fe(II)], nickel [Ni(II)], and lead [Pb(II)] at
      concentrations ranging from 0.3 to 100 microM on the incision activity of Ape1 in
      the presence of 1 mM MgCl(subscript)2(/subscript). Pb(II) and Fe(II) inhibited
      Ape1 activity at each of the concentrations tested, with an
      IC(subscript)50(/subscript) (half-maximal inhibitory concentration) of 0.61 and
      1.0 microM, respectively. Cd(II) also inhibited Ape1 activity but only at
      concentrations > 10 microM. No inhibition was seen with As(III), Co(II), or
      Ni(II). A similar inhibition pattern was observed with the homologous Escherichia
      coli protein, exonuclease III, but no inhibition was seen with the structurally
      distinct AP endonuclease E. coli endonuclease IV, indicating a targeted effect of
      Pb(II), Fe(II), and Cd(II) on the Ape1-like repair enzymes. Excess nonspecific
      DNA did not abrogate the metal inactivation, suggesting a protein-specific
      effect. Notably, Cd(II), Fe(II), and Pb(II) [but not As(III), Co(II), or Ni(II)]
      inhibited AP endonuclease activity in whole-cell extracts but had no significant
      effect on single nucleotide gap filling, 5'-flap endonuclease, and nick ligation
      activities, supporting the idea of selective inactivation of Ape1 in cells. Our
      results are the first to identify a potential DNA repair enzyme target for lead
      and suggest a means by which these prevalent environmental metals may elicit
      their deleterious effects.

PMID- 15159210
TI  - Toxicogenomics through the eyes of informatics: conference overview and
      recommendations.
AB  - Virginia Bioinformatics Institute, in conjunction with National Institutes of
      Environmental Health Sciences, hosted a conference, "Toxicogenomics through the
      Eyes of Informatics," in Bethesda, Maryland, USA, on 12-13 May 2003. Researchers
      around the world met to discuss how the application of bioinformatics tools,
      methodologies, and technologies will enhance our understanding of how cells and
      organisms respond to toxins. Conference topics included statistical methods,
      quantitative molecular data sets, computational algorithms for data analysis,
      computational modeling and simulation, challenges and opportunities in
      computational biology, and information technology infrastructure for data and
      tool management. This meeting report is a summary of conference presentations,
      survey results, current toxicogenomics concerns, and future directions of the
      toxicogenomics community. In conclusion this report discusses toxicogenomics as
      related to environmental agents, cell-chemical reactions, and gene-environment
      interactions.

PMID- 15159211
TI  - Metabolomics--a new exciting field within the "omics" sciences.

PMID- 15159213
TI  - Drawing comparisons at Duke.

PMID- 15159215
TI  - Hexachlorobenzene exposure: widespread toxicant produces pervasive effects.

PMID- 15159214
TI  - Metabolomics: what's happening downstream of DNA.

PMID- 15159216
TI  - Pseudopollen in Dendrobium unicum Seidenf. (Orchidaceae): reward or deception?
AB  - BACKGROUND AND AIMS: In 1987, Kjellsson and Rasmussen described the labellar
      trichomes of Dendrobium unicum Seidenf. and proposed that these hairs function as
      pseudopollen. Pseudopollen is a mealy material that superficially resembles
      pollen, is usually laden with food substances and is formed when labellar hairs
      either fragment into individual cells or become detached from the labellum.
      However, the trichomes of D. unicum are very different from pseudopollen-forming
      hairs found in other orchid genera such as Maxillaria and Polystachya. Moreover,
      Kjellsson and Rasmussen were unable to demonstrate the presence of food
      substances within these trichomes and argued that even in the absence of food
      substances, the hairs, in that they superficially resemble pollen, can still
      attract insects by deceit. The aim of this paper is to investigate whether the
      labellar trichomes of D. unicum contain food reserves and thus reward potential
      pollinators or whether they are devoid of foods and attract insects solely by
      mimicry. METHODS: Light microscopy, histochemistry and transmission electron
      microscopy. KEY RESULTS: Dendrobium unicum produces pseudopollen. Pseudopollen
      here, however, differs from that previously described for other orchid genera in
      that the pseudopollen-forming trichomes consist of a stalk cell and a 'head' of
      component cells that separate at maturity, in contrast to Maxillaria and some
      Polystachya spp. where pseudopollen is formed by the fragmentation of moniliform
      hairs. Moreover, the pseudopollen of Maxillaria and Polystachya largely contains
      protein, whereas in D. unicum the main food substance is starch. CONCLUSIONS:
      Flowers of D. unicum, rather than attracting insects solely by deceit may also
      reward potential pollinators.

PMID- 15159217
TI  - Night temperature has a minimal effect on respiration and growth in rapidly
      growing plants.
AB  - BACKGROUND AND AIMS: Carbon gain depends on efficient photosynthesis and adequate
      respiration. The effect of temperature on photosynthetic efficiency is well
      understood. In contrast, the temperature response of respiration is based almost
      entirely on short-term (hours) measurements in mature organisms to develop Q(10)
      values for maintenance and whole-plant respiration. These Q(10) values are then
      used to extrapolate across whole life cycles to predict the influence of
      temperature on plant growth. METHODS: In this study, night temperature in young,
      rapidly growing plant communities was altered from 17 to 34 degrees C for up to
      20 d. Day temperature was maintained at 25 degrees C. CO(2) gas-exchange was
      continuously monitored in ten separate chambers to quantify the effect of night
      temperature on respiration, photosynthesis and the efficiency of carbon gain
      (carbon use efficiency). KEY RESULTS: Respiration increased only 20-46 % for each
      10 degrees C rise in temperature (total respiratory Q(10) of between 1.2 to about
      1.5). This change resulted in only a 2-12 % change in carbon use efficiency, and
      there was no effect on cumulative carbon gain or dry mass. No acclimation of
      respiration was observed after 20 d of treatment. CONCLUSIONS: These findings
      indicate that whole-plant respiration of rapidly growing plants has a small
      sensitivity to temperature, and that the sensitivity does not change among the
      species tested, even after 20 d of treatment. Finally, the results support
      respiration models that separate respiration into growth and maintenance
      components.

PMID- 15159218
TI  - Glucose localization in maize ovaries when kernel number decreases at low water
      potential and sucrose is fed to the stems.
AB  - BACKGROUND AND AIMS: Around the time of anthesis, young ovary development in
      maize (Zea mays) is vulnerable to 2 or 3 d of water deficits that inhibit
      photosynthesis. Abortion can result, and fewer kernels are produced. A breakdown
      of stored ovary starch is associated with the abortion and was investigated in
      the present study by localizing the breakdown product glucose in the ovaries.
      METHODS: Ovary glucose was localized with fluorescent Resorufin. Insoluble
      invertase was localized in vivo and soluble invertase in situ. Sucrose was
      infused into the stems to vary the sugar flux to the ovaries. KEY RESULTS: At
      high water potential (high Psi(w)), photosynthesis was rapid in the parent. The
      upper pedicel of the ovaries had a high activity of insoluble acid invertase and
      a large amount of glucose and starch. Because the invertase was wall-bound,
      sucrose hydrolysis appeared to occur in the pedicel apoplast. Soluble invertase
      was undetected inside the pedicel cells but was present in the nucellus cells
      where low concentrations of glucose occurred. This created a glucose gradient
      between pedicel and nucellus that favoured glucose uptake by the developing
      ovary. At low Psi(w), photosynthesis was inhibited, pedicel glucose and starch
      were depleted, the glucose gradient became negligible, and abortion occurred.
      When sucrose was fed, glucose, starch and the glucose gradient were maintained
      somewhat and were normally distributed in the ovaries. Abortion was diminished.
      CONCLUSIONS: The apoplast hydrolysis of sucrose unloaded from phloem is similar
      to that described by others during later development when embryo and endosperm
      are present and separated from the parent by an apoplast. The disappearance of
      the glucose gradient at low Psi(w) may have inhibited glucose movement into the
      ovary. The low glucose in the ovaries may have a role in the abortion response.

PMID- 15159219
TI  - Micromorphological studies on seeds of orobanche species from the iberian
      peninsula and the balearic islands, and their systematic significance.
AB  - BACKGROUND AND AIMS: Previous research has made clear the intrinsic taxonomic
      difficulties in identifying species in the genus Orobanche. The aim of this
      study, therefore, was to investigate the systematic utility of seed
      characteristics. METHODS: Light and scanning electron microscopy was used to
      examine the seeds of 33 taxa of Orobanche from the Iberian Peninsula and the
      Balearic Islands. KEY RESULTS: Characters such as size, shape and ornamentation
      of the seeds were not found to be very useful in differentiation of taxa;
      however, other characters of the epidermal seed coat cells proved to be very
      helpful in this respect. Ornamentation of the periclinal walls could be used to
      discriminate four morphological types. Other features related to the anticlinal
      walls of the cells, such as thickness, presence/absence of a narrow trough, or
      relative depth, all contributed to the characterization of a large number of
      species. CONCLUSIONS: The usefulness of micromorphological studies on seeds of
      Orobanche in relation to differentiating taxa is demonstrated, and a key is
      provided to distinguish species or groups of species.

PMID- 15159220
TI  - Cardiovascular disease risk in women with diabetes needs attention.

PMID- 15159221
TI  - Energy requirements during pregnancy: old questions and new findings.

PMID- 15159222
TI  - Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of
      potential mechanisms.
AB  - Increasing evidence from animal and in vitro studies indicates that n-3 fatty
      acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic
      acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit
      carcinogenesis. The epidemiologic data on the association between fish
      consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk
      are, however, somewhat less consistent. This review highlights current knowledge
      of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids.
      Moreover, a possible explanation of why some epidemiologic studies failed to find
      an association between n-3 fatty acid intake and cancer risk is provided. Several
      molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process
      have been proposed. These include suppression of arachidonic acid-derived
      eicosanoid biosynthesis; influences on transcription factor activity, gene
      expression, and signal transduction pathways; alteration of estrogen metabolism;
      increased or decreased production of free radicals and reactive oxygen species;
      and mechanisms involving insulin sensitivity and membrane fluidity. Further
      studies are needed to evaluate and verify these mechanisms in humans to gain more
      understanding of the effects of n-3 fatty acid intake on cancer risk.

PMID- 15159223
TI  - Biomarkers of satiation and satiety.
AB  - This review's objective is to give a critical summary of studies that focused on
      physiologic measures relating to subjectively rated appetite, actual food intake,
      or both. Biomarkers of satiation and satiety may be used as a tool for assessing
      the satiating efficiency of foods and for understanding the regulation of food
      intake and energy balance. We made a distinction between biomarkers of satiation
      or meal termination and those of meal initiation related to satiety and between
      markers in the brain [central nervous system (CNS)] and those related to signals
      from the periphery to the CNS. Various studies showed that physicochemical
      measures related to stomach distension and blood concentrations of
      cholecystokinin and glucagon-like peptide 1 are peripheral biomarkers associated
      with meal termination. CNS biomarkers related to meal termination identified by
      functional magnetic resonance imaging and positron emission tomography are
      indicators of neural activity related to sensory-specific satiety. These measures
      cannot yet serve as a tool for assessing the satiating effect of foods, because
      they are not yet feasible. CNS biomarkers related to satiety are not yet specific
      enough to serve as biomarkers, although they can distinguish between extreme
      hunger and fullness. Three currently available biomarkers for satiety are
      decreases in blood glucose in the short term (<5 min), which have been shown to
      be involved in meal initiation; leptin changes during longer-term (>2-4 d)
      negative energy balance; and ghrelin concentrations, which have been implicated
      in both short-term and long-term energy balance. The next challenge in this
      research area is to identify food ingredients that have an effect on biomarkers
      of satiation, satiety, or both. These ingredients may help consumers to maintain
      their energy intake at a level consistent with a healthy body weight.

PMID- 15159224
TI  - Combined effects of energy density and portion size on energy intake in women.
AB  - BACKGROUND: Increases in both the portion size and energy density of food have
      both been shown to increase energy intake, but the combined effects of such
      increases have not been investigated. OBJECTIVE: The objective was to determine
      the combined effects of energy density and portion size on energy intake in
      women. DESIGN: This study used a within-subjects design. Once a week for 6 wk, 39
      women were served breakfast, lunch, and dinner ad libitum. The main entree at
      lunch was formulated in 2 versions that varied in energy density (5.23 or 7.32
      kJ/g), each of which was served in 3 different portion sizes (500, 700, or 900
      g). The 2 versions were matched for macronutrient composition and palatability.
      Breakfast and dinner were standard meals. RESULTS: Increases in portion size and
      energy density led to independent and additive increases in energy intake (P
      <0.0001). Subjects consumed 56% more energy (925 kJ) when served the largest
      portion of the higher energy-dense entree than when served the smallest portion
      of the lower energy-dense entree. Subjects did not compensate for the additional
      intake by eating less at the subsequent meal. Despite substantial differences in
      energy intake, no systematic differences in ratings of hunger and fullness across
      conditions were observed. CONCLUSIONS: The energy density and the portion size of
      a food act independently to affect energy intake. The findings indicate that
      large portions of foods with a high energy density may facilitate the
      overconsumption of energy.

PMID- 15159225
TI  - Dietary fatty acids affect plasma markers of inflammation in healthy men fed
      controlled diets: a randomized crossover study.
AB  - BACKGROUND: The effect of individual dietary fatty acids on emerging risk factors
      for cardiovascular disease that are associated with subclinical inflammation is
      unknown. OBJECTIVE: The goal was to evaluate the role of dietary fat and specific
      fatty acids, especially trans fatty acids, in altering concentrations of markers
      of inflammation in humans fed controlled diets. DESIGN: In a randomized crossover
      design, 50 men consumed controlled diets for 5 wk that provided 15% of energy
      from protein, 39% of energy from fat, and 46% of energy from carbohydrate. Eight
      percent of fat or fatty acids was replaced across diets with the following:
      cholesterol, oleic acid, trans fatty acids (TFAs), stearic acid (STE), TFA+STE
      (4% of energy each), and 12:0-16:0 saturated fatty acids (LMP). RESULTS:
      Fibrinogen concentrations were higher after consumption of the diet enriched in
      stearic acid than after consumption of the carbohydrate diet. C-reactive protein
      concentrations were higher after consumption of the TFA diet than after
      consumption of the carbohydrate diet, but were not significantly different after
      consumption of the TFA and TFA+STE diets than after consumption of the LMP diet.
      Interleukin 6 concentrations were lower after consumption of the oleic acid diet
      than after consumption of the LMP, TFA, and STE diets. E-selectin concentrations
      were higher after consumption of the TFA diet than after consumption of the
      carbohydrate diet. Consumption of the TFA but not the TFA+STE diet resulted in
      higher E-selectin concentrations than did the LMP diet. CONCLUSIONS: These data
      provide evidence that dietary fatty acids can modulate markers of inflammation.
      Although stearic acid minimally affects LDL cholesterol, it does appear to
      increase fibrinogen concentrations.

PMID- 15159226
TI  - Moderate fish-oil supplementation reverses low-platelet, long-chain n-3
      polyunsaturated fatty acid status and reduces plasma triacylglycerol
      concentrations in British Indo-Asians.
AB  - BACKGROUND: The mechanisms involved in the increased mortality from coronary
      artery disease in British Indo-Asians are not well understood. OBJECTIVES: This
      study aimed to investigate whether British Indo-Asian Sikhs have higher plasma
      triacylglycerol concentrations, lower platelet phospholipid levels, and lower
      dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age
      and weight-matched Europeans and whether moderate dietary fish-oil intake can
      reverse these differences. DESIGN: A randomized, double-blind, placebo
      controlled, parallel, fish-oil intervention study was performed. After a 2-wk run
      in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive
      either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g
      docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk.
      RESULTS: At baseline, the Indo-Asians had significantly higher plasma
      triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet
      phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA
      and DHA) than did the Europeans. A significant decrease in plasma
      triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid
      arachidonic acid concentrations and a significant increase in plasma HDL
      concentrations and platelet phospholipid EPA and DHA levels were observed after
      fish-oil supplementation. No significant effect of ethnicity on the responses to
      fish-oil supplementation was observed. CONCLUSIONS: Moderate fish-oil
      supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA
      levels in Indo-Asians and should be considered as an important, yet simple,
      dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic
      lipoprotein phenotype.

PMID- 15159227
TI  - Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long
      chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol
      reduction in Indian Asians.
AB  - BACKGROUND: Indian Asians in Western countries have a higher rate of coronary
      artery disease than do the indigenous white populations, and this higher rate may
      be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids
      (PUFAs). OBJECTIVE: The objective of the study was to test the hypothesis that a
      high background dietary intake of n-6 PUFA attenuates the effects of fish-oil
      supplementation on insulin sensitivity and associated blood lipids of the
      metabolic syndrome. DESIGN: Twenty-nine Indian Asian men were recruited to
      participate in a 12-wk dietary intervention trial. Volunteers were randomly
      assigned to receive either a moderate or a high n-6 PUFA diet featuring modified
      oils and spreads over a 6-wk period. After this 6-wk period, both groups were
      supplemented with 4.0 g fish oil/d (2.5 g eicosapentaenoic acid + docosahexaenoic
      acid) for an additional 6 wk in combination with the dietary treatment.
      Volunteers participated in a postprandial study and an insulin sensitivity test
      after the 6-wk dietary intervention and again after the fish-oil supplementation
      period. RESULTS: There was no significant time x treatment interaction for blood
      lipids or insulin action after dietary intervention with the moderate or high n-6
      PUFA diets in combination with fish oil. After the 6-wk period of fish oil
      supplementation, fasting and postprandial plasma triacylglycerol concentrations
      decreased significantly. CONCLUSION: The background dietary n-6 PUFA
      concentration did not modulate the effect of fish-oil supplementation on blood
      lipids or measures of insulin sensitivity in this ethnic group.

PMID- 15159228
TI  - Low plasma vitamin B-6 concentrations and modulation of coronary artery disease
      risk.
AB  - BACKGROUND: Low concentrations of pyridoxal-5'-phosphate (PLP), the active
      metabolite of vitamin B-6, are associated with high C-reactive protein (CRP)
      concentrations. Both low PLP and elevated inflammatory markers, such as high
      sensitivity CRP (hs-CRP) and fibrinogen, are related to higher risk of coronary
      artery disease (CAD). OBJECTIVES: The objectives were to evaluate the relation
      between PLP and acute-phase reactants in affecting CAD risk and to estimate the
      risk of CAD related to low plasma PLP, either alone or in combination with high
      concentrations of acute-phase reactants and other classic risk factors for CAD.
      DESIGN: A case-control study was conducted with 742 participants: 475 with severe
      multivessel CAD and 267 free from coronary atherosclerosis (CAD-free). We
      measured plasma PLP, fibrinogen, hs-CRP, and serum lipid concentrations and all
      major biochemical CAD risk factors, including total homocysteine. RESULTS: A
      significant, inverse, graded relation was observed between PLP and both hs-CRP
      and fibrinogen (P < 0.001). The prevalence of PLP concentrations in the lower
      half of the population (<50th percentile: 36.3 nmol/L) was significantly higher
      among CAD patients than among CAD-free subjects (P < 0.001). The odds ratio for
      CAD risk related to low PLP concentrations after adjustments for the major
      classic CAD risk factors, including hs-CRP and fibrinogen, was 1.89 (95% CI:
      1.18, 3.03; P = 0.008). The CAD risk as a result of low PLP was additive when
      considered in combination with elevated hs-CRP concentrations or with an
      increased ratio of LDL to HDL. CONCLUSION: Low plasma PLP concentrations are
      inversely related to major markers of inflammation and independently associated
      with increased CAD risk.

PMID- 15159229
TI  - Dietary fat and cholesterol and the risk of cardiovascular disease among women
      with type 2 diabetes.
AB  - BACKGROUND: Nutritional therapy is a cornerstone of diabetes management, but no
      epidemiologic studies have investigated the relation between specific dietary
      fatty acids and cholesterol and cardiovascular disease (CVD) risk among diabetic
      patients. OBJECTIVE: This study assessed the relation between specific dietary
      fatty acids and cholesterol and CVD risk among women with type 2 diabetes.
      DESIGN: Among 5672 women with type 2 diabetes from the Nurses' Health Study, diet
      was assessed prospectively and updated periodically. Relative risks of CVD were
      estimated from Cox proportional hazards analysis after adjustment for potential
      confounders. RESULTS: Between 1980 and 1998, we identified 619 new cases of CVD
      (nonfatal myocardial infarction, fatal coronary heart disease, and stroke). The
      relative risk (RR) of CVD for an increase of 200 mg cholesterol/1000 kcal was
      1.37 (95% CI: 1.12, 1.68; P = 0.003). Each 5% of energy intake from saturated
      fat, as compared with equivalent energy from carbohydrates, was associated with a
      29% greater risk of CVD (RR: 1.29; 95% CI: 1.02, 1.63; P = 0.04). The ratio of
      polyunsaturated to saturated fat (P:S) was inversely associated with the risk of
      fatal CVD. We estimated that replacement of 5% of energy from saturated fat with
      equivalent energy from carbohydrates or monounsaturated fat was associated with a
      22% or 37% lower risk of CVD, respectively. CONCLUSIONS: A higher intake of
      cholesterol and saturated fat and a low P:S were related to increased CVD risk
      among women with type 2 diabetes. Among diabetic persons, replacement of
      saturated fat with monounsaturated fat may be more effective in lowering CVD risk
      than is replacement with carbohydrates.

PMID- 15159230
TI  - Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but
      not in protein mass.
AB  - BACKGROUND: Tuberculosis is an important cause of wasting. The functional
      consequences of wasting and recovery may depend on the distribution of lost and
      gained nutrient stores between protein and fat masses. OBJECTIVE: The goal was to
      study nutrient partitioning, ie, the proportion of weight change attributable to
      changes in fat mass (FM) versus protein mass (PM), during antimycobacterial
      treatment. DESIGN: Body-composition measures were made of 21 men and 9 women with
      pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All
      subjects underwent dual-energy X-ray absorptiometry and deuterium bromide
      dilution tests, and a four-compartment model of FM, total body water (TBW), bone
      minerals (BM), and PM was derived. The ratio of PM to FM at any time was
      expressed as the energy content (p-ratio). Changes in the p-ratio were related to
      disease severity as measured by radiologic criteria. RESULTS: Patients gained 10%
      in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44%
      gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results
      were similar in men and women. The p-ratio decreased from baseline to month 1 and
      then fell further by month 6. Radiologic disease severity was not correlated with
      changes in the p-ratio. CONCLUSIONS: Microbiological cure of tuberculosis does
      not restore PM within 6 mo, despite a strong anabolic response. Change in the p
      ratio is a suitable parameter for use in studying the effect of disease on body
      composition because it allows transformation of such effects into a normal
      distribution across a wide range of baseline proportion between fat and protein
      mass.

PMID- 15159231
TI  - Comparison of self-reported with objectively assessed energy expenditure in black
      and white women before and after weight loss.
AB  - BACKGROUND: Weight maintenance is less successful in black women than in white
      women after weight loss. OBJECTIVE: We compared objectively assessed total energy
      expenditure (TEE) with estimates of energy expenditure (EE) from self-reported
      physical activity (PA) in overweight black and white women before and after
      weight loss. We also compared those values with values in never-overweight
      control subjects. DESIGN: A total of 20 white and 21 black premenopausal women
      were evaluated while overweight and weight reduced; 20 white and 14 black control
      subjects (matched with women in the weight-reduced state) were evaluated once.
      Weight loss of >/=10 kg was achieved by energy restriction in the overweight
      subjects. The evaluations were as follows: body composition (dual-energy X-ray
      absorptiometry), free-living TEE (doubly labeled water), Tecumseh Occupational
      Activity Questionnaire, Minnesota Leisure Time PA Questionnaire, and Baecke
      Activity Questionnaire. RESULTS: Questionnaire estimates of TEE were
      overestimated when compared with TEE (P < 0.001). Overweight women overestimated
      TEE 49% more than did never-overweight control subjects. After weight loss, white
      women reduced overestimation of EE 48% (P < 0.05), so that their overestimation
      of EE was not different from that of black and white control subjects. Black
      women overestimated to the same extent both before and after weight loss.
      CONCLUSIONS: Premenopausal women overestimate PA estimates on questionnaires.
      Overestimation of PA in weight-reduced black women is greater than in weight
      reduced white women and never-overweight black and white women.

PMID- 15159232
TI  - Combining wheat bran with resistant starch has more beneficial effects on fecal
      indexes than does wheat bran alone.
AB  - BACKGROUND: Wheat bran (WB) increases fecal bulk and hastens colonic transit,
      whereas resistant starch (RS) has effects on colonic fermentation, including
      increasing concentrations of butyrate. OBJECTIVE: We hypothesized that a diet
      combining WB with RS would produce more favorable changes in fecal variables (eg,
      fecal bulk, rapid transit time, lower pH, and higher butyrate) than would WB
      alone. DESIGN: This was a randomized crossover block-design study for which 20
      volunteers with a family history of colorectal cancer were recruited. The study
      included 3 diets: control, WB (12 g fiber/d), and WBRS (12 g WB fiber/d plus 22 g
      RS/d), each continued for 3 wk. In each diet, the major source of protein was
      lean red meat. During 5 consecutive days (days 15-19) of each dietary period, the
      subjects collected their total fecal output for analysis. RESULTS: The WB diet
      resulted in greater fecal output (by 23% and 21% for wet and dry weights,
      respectively) and a lesser transit time (-11 h) than did the control diet but did
      not have major effects on fermentation variables. Compared with the control diet,
      the WBRS diet resulted in greater fecal output (by 56%) and a shorter transit
      time (-10 h), lower fecal pH (-0.15 units), higher fecal concentration (by 14%)
      and daily excretion (by 101%) of acetate, higher fecal concentration (by 79%) and
      daily excretion (by 162%) of butyrate, a higher fecal ratio of butyrate to total
      short-chain fatty acids (by 45%), and lower concentrations of total phenols (
      34%) and ammonia (-27%). CONCLUSIONS: Combining WB with RS had more benefits than
      did WB alone. This finding may have important implications for the dietary
      modulation of luminal contents, especially in the distal colon (the most common
      site of tumor formation).

PMID- 15159233
TI  - Low antioxidant vitamin intakes are associated with increases in adverse effects
      of chemotherapy in children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Chemotherapy leads to an increase in reactive oxygen species, which
      stresses the antioxidant defense system. Children with acute lymphoblastic
      leukemia rarely are overtly malnourished, which makes this population ideal for
      an investigation of the relations between dietary antioxidant consumption, plasma
      antioxidant concentrations, and chemotherapy-induced toxicity. OBJECTIVE: This
      study was conducted to investigate the effect of therapy on antioxidant intakes
      in children with acute lymphoblastic leukemia, the relation between dietary
      antioxidant intakes and plasma antioxidant concentrations, and the relation
      between the incidence of side effects due to treatment and antioxidant intake.
      DESIGN: We conducted a 6-mo observational study of 103 children with acute
      lymphoblastic leukemia. Plasma micronutrient concentrations, dietary intakes, and
      incidence of side effects of chemotherapy were ascertained at diagnosis and after
      3 and 6 mo of therapy. RESULTS: Throughout the 6-mo study period, subjects
      ingested vitamin E, total carotenoid, beta-carotene, and vitamin A in amounts
      that were 66%, 30%, 59%, and 29%, respectively, of the US recommended dietary
      allowance or of the amounts specified in the third National Health and Nutrition
      Examination Survey. Greater vitamin C intakes at 6 mo were associated with fewer
      therapy delays, less toxicity, and fewer days spent in the hospital. Greater
      vitamin E intakes at 3 mo were associated with a lower incidence of infection.
      Greater beta-carotene intakes at 6 mo were associated with a decreased risk of
      toxicity. CONCLUSION: A large percentage of children undergoing treatment for
      acute lymphoblastic leukemia have inadequate intakes of antioxidants and vitamin
      A. Lower intakes of antioxidants are associated with increases in the adverse
      side effects of chemotherapy.

PMID- 15159234
TI  - Long-term high copper intake: effects on indexes of copper status, antioxidant
      status, and immune function in young men.
AB  - BACKGROUND: Short-term high copper intake does not appear to affect indexes of
      copper status or functions related to copper status, but the effects of long-term
      high copper intake are unknown. OBJECTIVE: A study was conducted in men to
      determine the effect of long-term high copper intake on indexes of copper status,
      oxidant damage, and immune function. DESIGN: Nine men were confined to a
      metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing
      an average of 1.6 mg Cu/d. The men continued the study under free-living
      conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men
      then returned to the MRU for 18 d of the same diet as during the first period,
      except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity,
      ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity,
      erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary
      thiobarbituric acid-reactive substances were measured during each MRU period.
      RESULTS: Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase
      were significantly higher at the end of the second MRU period than at the end of
      the first. Urinary copper excretion, hair copper concentrations, and urinary
      thiobarbituric acid-reactive substances were significantly higher during the
      second MRU period than during the first. Polymorphonuclear cell count, the
      percentage of white blood cells, lymphocyte count, and interleukin 2R were
      affected by copper supplementation. Antibody titer for the Beijing strain of
      influenza virus was significantly lower in supplemented subjects after
      immunization than in unsupplemented control subjects. CONCLUSIONS: Under highly
      controlled conditions, long-term high copper intake results in increases in some
      indexes of copper status, alters an index of oxidant stress, and affects several
      indexes of immune function. The physiologic implications of these changes are
      unknown.

PMID- 15159235
TI  - Lutein, zeaxanthin, macular pigment, and visual function in adult cystic fibrosis
      patients.
AB  - BACKGROUND: Pancreatic insufficiency in cystic fibrosis (CF), even with
      replacement pancreatic enzyme therapy, is often associated with decreased
      carotenoid absorption. Because the macular pigment of the retina is largely
      derived from 2 carotenoids, lutein and zeaxanthin, the decreased serum
      concentrations seen in CF may have consequences for ocular and retinal health
      OBJECTIVES: Our aims were to determine plasma carotenoid concentrations,
      determine absorption and distribution of macular pigment, and assess retinal
      health and visual function in CF patients. DESIGN: In 10 adult CF patients (ages
      21-47 y) and 10 age- and sex-matched healthy control subjects, we measured
      macular pigment density in vivo, measured serum lutein and zeaxanthin
      concentrations, and comprehensively assessed visual performance (including
      contrast sensitivity, color discrimination, and retinal function) under
      conditions of daylight illumination. RESULTS: Serum lutein and zeaxanthin were
      significantly reduced (P < 0.005) in CF patients ( +/- SD: 87 +/- 36.1 and 27 +/-
      15.8 nmol/L, respectively) compared with control subjects (190 +/- 72.1 and 75 +/
      23.6 nmol/L, respectively). Although macular pigment optical density was
      significantly lower (P < 0.0001) in the CF group (0.24 +/- 0.11) than in the
      control group (0.53 +/- 0.12), no significant differences in visual function were
      observed. CONCLUSIONS: Adults with CF have dramatically low serum and macular
      concentrations of carotenoids (lutein and zeaxanthin), but their ocular status
      and visual function are surprisingly good. The clinical implications of low
      plasma concentrations of carotenoids in CF are yet to be clarified.

PMID- 15159236
TI  - Zinc absorption from low-phytate hybrids of maize and their wild-type isohybrids.
AB  - BACKGROUND: Identification of allelic variants in a single gene that determine
      the phytate content of maize kernels and the subsequent breeding of low-phytate
      maize have facilitated studies designed to determine quantitatively the effects
      of maize phytate on the bioavailability of minerals in maize. OBJECTIVE: The
      objective was to determine the relation between the fractional absorption of zinc
      (FAZ) and the phytate content and phytate:zinc molar ratios of maize tortillas
      prepared from hybrids with different phytate contents. DESIGN: Six healthy adults
      were fed, as the only food for 2 d, maize tortillas prepared from 1 of 2 low
      phytate mutants: lpa1-1 (lpa1-1-LP) or Nutridense Low Phytate (ND-LP), which have
      phytate reductions of approximately 60% and approximately 80%, respectively,
      compared with their respective wild-type isohybrids. Four additional subjects
      were fed tortillas prepared from the corresponding wild-type isohybrids (lpa1-1
      WT and ND-WT) according to the same study design. Meals were extrinsically
      labeled with zinc stable isotopes, and FAZ was determined with a dual-isotope
      tracer ratio technique. Overall FAZ values were examined in relation to dietary
      phytate and phytate:zinc molar ratios by using a mixed nonlinear regression
      model. RESULTS: The mean (+/-SD) FAZ values from tortillas prepared from ND-LP,
      lpa1-1-LP, lpa1-1-WT, and ND-WT were 0.38 +/- 0.07, 0.28 +/- 0.04, 0.15 +/- 0.07,
      and 0.13 +/- 0.05, respectively. A negative relation (P < 0.001) was found
      between FAZ and both dietary phytate and the phytate:zinc molar ratio. The effect
      of dietary zinc (8-14 mg Zn/d) under these experimental conditions was not
      significant. CONCLUSIONS: FAZ from maize tortillas is positively related to the
      extent of phytate reduction achieved with low-phytate hybrids.

PMID- 15159237
TI  - The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress
      and antioxidative defense in healthy nonsmokers.
AB  - BACKGROUND: Fruit and vegetables contain both nutritive and nonnutritive factors
      that might contribute to redox (antioxidant and prooxidant) actions. OBJECTIVE:
      We investigated the relative influence of nutritive and nonnutritive factors in
      fruit and vegetables on oxidative damage and enzymatic defense. DESIGN: A 25-d
      intervention study with complete control of dietary intake was performed in 43
      healthy male and female nonsmokers who were randomly assigned to 1 of 3 groups.
      In addition to a basic diet devoid of fruit and vegetables, the fruit and
      vegetables (Fruveg) group received 600 g fruit and vegetables/d; the placebo
      group received a placebo pill, and the supplement group received a vitamin pill
      designed to contain vitamins and minerals corresponding to those in 600 g fruit
      and vegetables. Biomarkers of oxidative damage to protein and lipids and of
      antioxidant nutrients and defense enzymes were determined before and during
      intervention. RESULTS: Plasma lipid oxidation lag times increased during
      intervention in the Fruveg and supplement groups, and the increase was
      significantly higher in the former. Plasma protein carbonyl formation at lysine
      residues also increased in both of these groups. Glutathione peroxidase activity
      increased in the Fruveg group only. Other markers of oxidative damage, oxidative
      capacity, or antioxidant defense were largely unaffected by the intervention.
      CONCLUSIONS: Fruit and vegetables increase erythrocyte glutathione peroxidase
      activity and resistance of plasma lipoproteins to oxidation more efficiently than
      do the vitamins and minerals that fruit and vegetables are known to contain.
      Plasma protein carbonyl formation at lysine residues increases because of the
      vitamins and minerals in fruit and vegetables.

PMID- 15159238
TI  - Human milk as a source of ascorbic acid: no enhancing effect on iron
      bioavailability from a traditional complementary food consumed by Bangladeshi
      infants and young children.
AB  - BACKGROUND: Iron bioavailability from traditional complementary foods based on
      cereals and legumes can be expected to be low unless ascorbic acid-rich foods are
      incorporated into the diet. OBJECTIVE: We evaluated human milk as a source of
      ascorbic acid for enhancing iron bioavailability from khichuri, a complementary
      food based on rice and lentils. DESIGN: Erythrocyte incorporation of stable iron
      isotopes 14 d after administration was used as a proxy for iron bioavailability.
      Children aged 8-18 mo (n = 31) were breastfed (32-90 mg ascorbic acid/kg human
      milk) immediately after intake of 4 servings of khichuri labeled with (57)Fe
      (test meal B) and were offered water after intake of 4 servings of khichuri
      labeled with (58)Fe (test meal A). Test meals were fed twice daily during 4 d in
      the order of AABBAABB or BBAABBAA. RESULTS: The mean intakes of human milk and
      ascorbic acid were 274 g (range: 60-444 g) and 14 mg (range: 4-28 mg,
      respectively). The mean molar ratio of ascorbic acid to iron was 2.3 (range: 0.7
      4.6). The geometric mean iron bioavailability from khichuri fed with or without
      human milk was 6.2% and 6.5%, respectively (P = 0.76, paired Student's t test).
      CONCLUSIONS: Although human milk contributed significant quantities of ascorbic
      acid, no significant difference in iron bioavailability was found between
      khichuri consumed with water and that consumed with human milk. These results
      indicate either that the molar ratio of ascorbic acid to iron was not
      sufficiently high to overcome the inhibitory effect of phytic acid in khichuri
      (30 mg/serving) or that components of human milk modified the influence of
      ascorbic acid on iron bioavailability.

PMID- 15159239
TI  - Energy requirements during pregnancy based on total energy expenditure and energy
      deposition.
AB  - BACKGROUND: Energy requirements during pregnancy remain controversial because of
      uncertainties regarding maternal fat deposition and reductions in physical
      activity. OBJECTIVE: This study was designed to estimate the energy requirements
      of healthy underweight, normal-weight, and overweight pregnant women and to
      explore energetic adaptations to pregnancy. DESIGN: The energy requirements of 63
      women [17 with a low body mass index (BMI; in kg/m(2)), 34 with a normal BMI, and
      12 with a high BMI] were estimated at 0, 9, 22, and 36 wk of pregnancy and at 27
      wk postpartum. Basal metabolic rate (BMR) was measured by calorimetry, total
      energy expenditure (TEE) by doubly labeled water, and activity energy expenditure
      (AEE) as TEE - BMR. Energy deposition was calculated from changes in body protein
      and fat. Energy requirements equaled the sum of TEE and energy deposition.
      RESULTS: BMR increased gradually throughout pregnancy at a mean (+/-SD) rate of
      10.7 +/- 5.4 kcal/gestational week, whereas TEE increased by 5.2 +/- 12.8
      kcal/gestational week, which indicated a slight decrease in AEE. Energy costs of
      pregnancy depended on BMI group. Although total protein deposition did not differ
      significantly by BMI group (mean for the 3 groups: 611 g protein), FM deposition
      did (5.3, 4.6, and 8.4 kg FM in the low-, normal-, and high-BMI groups; P =
      0.02). Thus, energy costs differed significantly by BMI group (P = 0.02). In the
      normal-BMI group, energy requirements increased negligibly in the first
      trimester, by 350 kcal/d in the second trimester, and by 500 kcal/d in the third
      trimester. CONCLUSION: Extra energy intake is required by healthy pregnant women
      to support adequate gestational weight gain and increases in BMR, which are not
      totally offset by reductions in AEE.

PMID- 15159240
TI  - Children's food consumption during television viewing.
AB  - BACKGROUND: Television viewing is associated with childhood obesity. Eating
      during viewing and eating highly advertised foods are 2 of the hypothesized
      mechanisms through which television is thought to affect children's weight.
      OBJECTIVES: Our objectives were to describe the amounts and types of foods that
      children consume while watching television, compare those types with the types
      consumed at other times of the day, and examine the associations between
      children's body mass index (BMI) and the amounts and types of foods consumed
      during television viewing. DESIGN: Data were collected from 2 samples. The first
      sample consisted of ethnically diverse third-grade children, and the second
      consisted predominantly of Latino fifth-grade children. Three nonconsecutive 24-h
      dietary recalls were collected from each child. For each eating episode reported,
      children were asked whether they had been watching television. Height and weight
      were measured by using standard methods and were used to calculate BMI. RESULTS:
      On weekdays and weekend days, 17-18% and approximately 26% of total daily energy,
      respectively, were consumed during television viewing in the 2 samples. Although
      the fat content of the foods consumed during television viewing did not differ
      significantly from that of the foods consumed with the television off, less soda,
      fast food, fruit, and vegetables were consumed with the television on. The amount
      of food consumed during television viewing was not associated with children's
      BMI, but in the third-grade sample, the fat content of foods consumed during
      television viewing was associated with BMI. CONCLUSIONS: A significant proportion
      of children's daily energy intake is consumed during television viewing, and the
      consumption of high-fat foods on weekends may be associated with BMI in younger
      children.

PMID- 15159241
TI  - Diet and blood pressure in 2.5-y-old Danish children.
AB  - BACKGROUND: Blood pressure tracks from childhood into adulthood, and early diet
      may have long-term effects on hypertension. OBJECTIVE: The study's aim was to
      investigate whether intakes of n-3 long-chain polyunsaturated fatty acids (n-3 LC
      PUFAs) during lactation and current intakes of macronutrients affect blood
      pressure in 2.5-y-old Danish children. DESIGN: Mothers (n =122) with low fish
      intakes were randomly assigned to receive supplementation with 4.5 g fish oil or
      olive oil/d during the first 4 mo of lactation. The trial also included 53
      mothers with high fish intakes. One hundred five of these women's children
      attended a 2.5-y follow-up examination at which anthropometric data and blood
      pressure were obtained. Mothers then kept a 7-d dietary record of food consumed
      by their children. A full set of data from 73 children was analyzed for effects
      of fish oil supplementation and cross-sectional correlations with current diet.
      RESULTS: We found no significant effect of the mothers' fish oil intakes during
      the first 4 mo of lactation on the blood pressure of the children 2.5 y later.
      Greater protein intakes measured as a percentage of energy were associated cross
      sectionally with significantly lower diastolic and systolic blood pressures in
      the children at age 2.5 y after control for outdoor temperature, age, sex,
      weight, and height (P = 0.028 and 0.035, respectively). Greater protein intakes
      measured as g/d were also associated with significantly lower systolic blood
      pressures (P = 0.008). A 1-SD increase in protein intake corresponded with a
      decrease of approximately 3 mm Hg in systolic blood pressure. CONCLUSION: The
      blood pressure of young Danish children was not significantly affected by intakes
      of n-3 LC-PUFAs via breast milk, but greater protein intakes at 2.5 y were
      associated with lower blood pressure.

PMID- 15159242
TI  - Relation of leptin pulse dynamics to fat distribution in HIV-infected patients.
AB  - BACKGROUND: HIV-infected patients are affected by changes in fat distribution,
      ie, significant losses of subcutaneous fat in association with metabolic
      abnormalities. OBJECTIVE: The objective was to investigate the relation between
      leptin secretion and subcutaneous fat loss in HIV-infected patients. DESIGN: We
      investigated leptin pulse dynamics, measured every 20 min overnight from 2000 to
      0800 in 41 HIV-infected patients with a mean (+/-SEM) age of 42.7 +/- 1.1 y and
      body mass index (in kg/m(2)) of 24.7 +/- 0.4 and in 20 healthy control subjects
      (age: 42.8 +/- 1.8 y; body mass index: 24.6 +/- 0.5). Leptin pulse variables were
      compared with total body fat, abdominal subcutaneous fat, and abdominal visceral
      fat in univariate and multivariate regression analyses. RESULTS: The number of
      leptin pulses was not significantly different between the HIV-infected and
      control subjects. Subcutaneous fat correlated significantly with mean leptin
      secretion (r = 0.72, P <0.0001), leptin pulse amplitude (r = 0.62, P <0.0001),
      and leptin nadir (r = 0.62, P <0.0001) in the HIV-infected patients. In stepwise
      regression modeling, subcutaneous fat (P <0.0001), but not visceral fat, was
      significantly associated with leptin secretion (overall R(2) for the model =
      0.57, P <0.0001) in the HIV-infected patients. For each 1-cm(2) decrease in
      abdominal subcutaneous fat area, leptin decreased by 0.044 ng/mL when visceral
      fat was controlled for. Subcutaneous fat was also significantly related to leptin
      in the control subjects. CONCLUSIONS: This is the first study to investigate the
      relation between fat distribution and leptin pulse dynamics in HIV-infected
      patients. There was a significant reduction in leptin secretion with subcutaneous
      fat loss in this population.

PMID- 15159243
TI  - Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid
      binding protein 2 gene is dependent on the type of fat ingested.
AB  - BACKGROUND: The alanine-for-threonine substitution at codon 54 (A54T
      polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been
      associated with hypertriglyceridemia and insulin resistance. Obese and diabetic
      T54 carriers have greater postprandial lipemia than do A54 homozygotes. The T54
      protein isoform is also associated with increased triacylglycerol secretion in
      vitro. OBJECTIVE: We investigated diet-gene interactions by measuring
      postprandial lipids, glucose, insulin, and C-peptide in healthy, nonobese A54
      homozygotes and T54 carriers after ingestion of 3 different fats. DESIGN: Eleven
      A54 homozygotes and 11 T54 carriers were given 3 oral-fat-tolerance tests
      (butter, safflower oil, and olive oil). Cholesterol and triacylglycerol were
      measured in plasma and in chylomicron fractions. RESULTS: There was no main
      effect of FABP2 genotype for chylomicron triacylglycerol, glucose, or C-peptide.
      The area under the insulin curve and the ratio of insulin to C-peptide were lower
      in T54 carriers than in A54 homozygotes [312 +/- 29 ( +/- SEM) compared with 425
      +/- 31 pmol. h/L (P = 0.05) and 0.23 +/- 0.03 compared with 0.40 +/- 0.05 (P =
      0.04), respectively], which suggests greater hepatic insulin clearance in T54
      carriers. An association between genotype and chylomicron cholesterol was seen
      only after olive oil: values were higher (P = 0.02) in T54 carriers (0.087 +/-
      0.006 mmol. h/L) than in A54 homozygotes (0.058 +/- 0.004 mmol. h/L). The main
      effect of fat was significant for the areas under the chylomicron cholesterol and
      chylomicron triacylglycerol curves [higher values for safflower (0.635 +/- 0.053
      and 2.48 +/- 0.30 mmol. h/L, respectively) and olive (0.592 +/- 0.052 and 2.48 +/
      0.32 mmol. h/L, respectively) oils than for butter (0.425 +/- 0.043 and 1.69 +/-
      0.20 mmol. h/L, respectively); P < 0.05]. CONCLUSIONS: The A54T polymorphism
      results in a diet-gene interaction: the T54 group had increased chylomicron
      cholesterol after olive oil only. Nevertheless, the greater hepatic insulin
      clearance in T54 carriers suggests that the polymorphism may not be deleterious
      in nonobese subjects.

PMID- 15159244
TI  - Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy
      overweight humans.
AB  - BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may
      reduce body fat mass (BFM) and increase lean body mass (LBM), but the long-term
      effect of CLA was not examined. OBJECTIVE: The objective of the study was to
      ascertain the 1-y effect of CLA on body composition and safety in healthy
      overweight adults consuming an ad libitum diet. DESIGN: Male and female
      volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were included
      in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3
      groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil).
      Change in BFM, as measured by dual-energy X-ray absorptiometry, was the primary
      outcome. Secondary outcomes included the effects of CLA on LBM, adverse events,
      and safety variables. RESULTS: Mean (+/- SD) BFM in the CLA-triacylglycerol and
      CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%, respectively, lower than that
      in the placebo group (P < 0.001). Subjects receiving CLA-FFA had 1.8 +/- 4.3%
      greater LBM than did subjects receiving placebo (P = 0.002). These changes were
      not associated with diet or exercise. LDL increased in the CLA-FFA group (P =
      0.008), HDL decreased in the CLA-triacylglycerol group (P = 0.003), and
      lipoprotein(a) increased in both CLA groups (P < 0.001) compared with month 0.
      Fasting blood glucose concentrations remained unchanged in all 3 groups. Glycated
      hemoglobin rose in all groups from month 0 concentrations, but there was no
      significant difference between groups. Adverse events did not differ
      significantly between groups. CONCLUSION: Long-term supplementation with CLA-FFA
      or CLA-triacylglycerol reduces BFM in healthy overweight adults.

PMID- 15159245
TI  - The Role of Conjugated Linoleic Acid in Human Health. Proceedings of a workshop.
      Winnipeg, Canada, March 13-15, 2003.

PMID- 15159246
TI  - Perspective on the safety and effectiveness of conjugated linoleic acid.
AB  - The amount of scientific literature on conjugated linoleic acid (CLA) is growing
      at a phenomenal rate. Animal studies and clinical trials indicate the possibility
      that CLA could be useful in improving human health in a number of areas, eg,
      controlling body fat gain and enhancing immunity while also reducing inflammation
      and other adverse effects typically associated with immune enhancement. The
      background of this growing research field and mechanistic insights from animal
      and cell culture experiments are briefly reviewed. Experimental and clinical data
      relating to the safety and effectiveness of CLA in humans are presented and
      discussed.

PMID- 15159247
TI  - Analysis of conjugated linoleic acid and trans 18:1 isomers in synthetic and
      animal products.
AB  - The chemistry of conjugated fatty acids, specifically octadecadienoic acids
      (18:2; commonly referred to as conjugated linoleic acid, or CLA), has provided
      many challenges to lipid analysts because of their unique physical properties and
      the many possible positional and geometric isomers. After the acid-labile
      properties of CLAs during analytic procedures were overcome, it became evident
      that natural products, specifically dairy fats, contain one dominant (c9,t11
      CLA), 3 intermediate (t7,c9-, t9,c11-, and t11,c13-CLA), and up to 20 more minor
      CLA isomers. The best analytic techniques to date include a combination of gas
      chromatography that uses 100-m highly polar capillary columns, silver ion-HPLC,
      and a combination of silver ion-thin-layer chromatography and gas chromatography
      to analyze the CLA and trans 18:1 isomers, because some of them serve as
      precursors of CLA in biological systems. These analytic techniques have assisted
      commercial suppliers to prepare pure CLA isomers and have permitted the
      evaluation of individual CLA isomers for their nutritional and biological
      activity in animal and human systems. It is increasingly evident that different
      CLA isomers have distinctly different physiologic and biochemical properties.
      These techniques are essential to evaluate dairy fats for their CLA content, to
      design experimental diets to increase the amount of CLA in dairy fats, and to
      determine the CLA profile in these CLA-enriched dairy fats. These improved
      techniques are used to evaluate the CLA profile in pork products from pigs fed
      different commercial CLA mixtures.

PMID- 15159248
TI  - Metabolic effects of conjugated linoleic acid in humans: the Swedish experience.
AB  - Conjugated linoleic acid (CLA) comprises a group of unsaturated fatty acid
      isomers with a variety of biological effects. CLA reduces body fat accumulation
      in animal models and has been ascribed significant effects on lipid and glucose
      metabolism. It has been suggested that the trans-10,cis-12 isomer is the active
      isomer with regard to antiobesity and insulin-sensitizing properties. The
      metabolic effects in humans are not well characterized. We have investigated and
      published the effects of CLA (given as the commercially available mixture and as
      the purified trans-10,cis-12 isomer) on anthropometry, lipid and glucose
      metabolism, and markers of lipid peroxidation. The results from those studies
      indicate that CLA might slightly decrease body fat in humans, particularly
      abdominal fat, but there is no effect on body weight or body mass index. There is
      no simultaneous improvement in lipid or glucose metabolism. Rather, the trans
      10,cis-12 CLA isomer unexpectedly caused significant impairment of the peripheral
      insulin sensitivity as well as of blood glucose and serum lipid concentrations.
      In addition, CLA markedly elevated lipid peroxidation. Thus, the metabolic
      effects of CLA in humans seem complex, and further studies, especially of
      specific isomers and of longer duration, are needed.

PMID- 15159249
TI  - Metabolic syndrome and effects of conjugated linoleic acid in obesity and
      lipoprotein disorders: the Quebec experience.
AB  - The health hazards of obesity are well established. However, the fact that all
      obese individuals are not at equal risk of developing a disease is being
      increasingly recognized. The regional distribution of body fat has been
      identified as an important component of the obesity-related health hazards. Among
      obese individuals, those who accumulate fat predominantly in the abdominal area
      are more likely to present several metabolic perturbations of the metabolic
      syndrome, such as increased plasma triacylglycerol and apolipoprotein B
      concentrations, an elevated ratio of total cholesterol to HDL cholesterol,
      reduced plasma HDL-cholesterol concentrations, and small, dense LDL particles.
      This short review focuses on the risk associated with specific features of
      metabolic syndrome with use of data from the Quebec Cardiovascular Study, an
      ongoing prospective study of traditional and nontraditional risk factors for
      ischemic heart disease in men. Recent data on the effect of conjugated linoleic
      acid on risk factors associated with metabolic syndrome are briefly reviewed.
      Data available to date suggest that conjugated linoleic acid might not be an
      appropriate dietary alternative for the treatment of metabolic syndrome and its
      complications.

PMID- 15159250
TI  - Dietary conjugated linoleic acid and body composition.
AB  - Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of
      conjugated dienoic derivatives of linoleic acid. The major dietary source of CLA
      for humans is ruminant meats, such as beef and lamb, and dairy products, such as
      milk and cheese. The major isomer of CLA in natural food is cis-9,trans-11
      (c9,t11). The commercial preparations contain approximately equal amounts of
      c9,t11 and trans-10,cis-12 (t10,c12) isomers. Studies have shown that CLA,
      specifically the t10,c12-isomer, can reduce fat tissue deposition and body lipid
      content but appears to induce insulin resistance and fatty liver and spleen in
      various animals. A few human studies suggest that CLA supplementation has no
      effect on body weight and could reduce body fat to a much lesser extent than in
      animals. To draw conclusions on this form of dietary supplementation and to
      ultimately make appropriate recommendations, further human studies are required.
      The postulated antiobesity mechanisms of CLA include decreased energy and food
      intakes, decreased lipogenesis, and increased energy expenditure, lipolysis, and
      fat oxidation. This review addresses recent studies of the effects of CLA on
      lipid metabolism, fat deposition, and body composition in both animals and humans
      as well as the mechanisms surrounding these effects.

PMID- 15159251
TI  - Insulin resistance-associated cardiovascular disease: potential benefits of
      conjugated linoleic acid.
AB  - Type 2 diabetes and associated cardiovascular disease have reached global
      epidemic proportions. Recent data from the World Health Organization
      Multinational Study of Vascular Disease in Diabetes indicate that cardiovascular
      disease is the leading cause of mortality (52% of deaths) in individuals with
      type 2 diabetes. Although insulin resistance plays a critical role in the
      pathogenesis of type 2 diabetes-related cardiovascular disease, other related
      risk factors often cluster in a single patient; the combination of insulin
      resistance and these risk factors is known as the metabolic syndrome. According
      to the World Health Organization definition, this constellation of risk factors
      includes hypertension, elevated plasma triacylglycerol, reduced HDL cholesterol,
      central obesity, and microalbuminuria. The Multiple Risk Factor Intervention
      Trial showed that, although diabetes or insulin resistance is an independent risk
      factor for cardiovascular disease mortality, these other components of the
      metabolic syndrome confer additive risk. Thus, to effectively address
      cardiovascular disease in persons with diabetes, intervention would ideally
      target all these factors. Conjugated linoleic acid could represent a candidate
      agent. The therapeutic potential of conjugated linoleic acid against insulin
      resistance-associated cardiovascular disease is discussed on the basis of the
      reported effects of conjugated linoleic acid on individual components of the
      metabolic syndrome.

PMID- 15159252
TI  - Dietary conjugated linoleic acid and insulin sensitivity and resistance in rodent
      models.
AB  - Dietary conjugated linoleic acid (CLA) is being investigated for beneficial
      effects for disease prevention and treatment in a variety of experimental models,
      including obesity and type 2 diabetes. To date, rodent studies suggest that trans
      10,cis-12 (t10,c12) CLA is associated with greater insulin resistance, despite
      lower body fat, and that a CLA mixture (and perhaps c9,t11) could be beneficial
      for the management of insulin resistance. Studies investigating the mechanisms by
      which CLA operates at the cellular level show that the primary targets for CLA
      are members of the nuclear receptor family, particularly the lipostat
      transcription factors peroxisome proliferator-activated receptor alpha
      (PPARalpha), PPARgamma, sterol regulatory element-binding protein 1c, and liver X
      receptor alpha. Consequently, the effects of CLA on glucose metabolism are likely
      secondary effects mediated through factors such as PPARgamma coactivator 1 that
      are controlled by these nuclear receptors. The different responses of normal
      compared with insulin-resistant obese rodents suggest that interactions of CLA
      isomers with the cellular components that contribute to development of metabolic
      syndrome require further investigation.

PMID- 15159253
TI  - Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density
      lipoprotein metabolism.
AB  - Conjugated linoleic acids (CLAs) are isomeric forms of the 18:2 fatty acid that
      contain conjugated sites of unsaturation. Although CLAs are minor components of
      the diet, they have many reported biological activities. For nearly a decade, the
      potential for CLA to modify the atherosclerotic process has been examined in
      animal models, and studies of supplementation of the human diet with CLA were
      started with the anticipation that such an intervention could also reduce the
      risk of cardiovascular disease. Central to the hypothesis is the expectation that
      dietary modification could alter plasma lipid and lipoprotein metabolism toward a
      more cardioprotective profile. This review examines the evidence in support of
      the hypothesis and the mechanistic studies that lend support for a role of CLA in
      hepatic lipid and lipoprotein metabolism. Although there are still limited
      studies in strong support of a role for CLA in the reduction of early
      atherosclerotic lesions, there has been considerable progress in defining the
      mechanisms of CLA action. CLA could primarily modulate the metabolism of fatty
      acids in the liver. The tools are now available to examine isomer-specific
      effects of CLA on hepatic lipid and lipoprotein metabolism and the potential of
      CLA to modify hepatic gene expression patterns. Additional animal and cell
      culture studies will increase our understanding of these unusual fatty acids and
      their potential for health benefits in humans.

PMID- 15159254
TI  - A test of Ockham's razor: implications of conjugated linoleic acid in bone
      biology.
AB  - The philosopher William of Ockham is recognized for the maxim that an assumption
      introduced to explain a phenomenon must not be multiplied beyond necessity, or
      that the simplest explanation is probably the correct explanation. The general
      truth is that conjugated linoleic acids (CLAs) are nutrients. However, the
      demonstration that these isomers of octadecadienoic acid protect against cancers
      in rodents stimulated curiosity that directed significant resources to
      characterize the biological functions of these fatty acids in cell and animal
      models. The benefits to human subjects given supplements of CLA were at best
      modest. The disappointing results in humans should be taken as an opportunity to
      critically evaluate all findings of CLA use and to consolidate the common actions
      of this nutrient so that future investigations focus on specific isomers and the
      most reasonable mechanisms. As such, the principal and consistently reported
      benefits of CLA have been in improving cancer outcomes, reducing body fat in
      growing animals, and modulating cell functions. Recognizing where related actions
      of CLA converge in specific disease conditions and physiologic states is how
      research efforts should be directed to minimize the pursuit of superfluous
      theories. Here, we briefly review the current biological effects of CLA and
      attempt to integrate their potential effect on the physiology and health of the
      skeletal system. Thus, the purpose of this review is to advance the science of
      CLA and to identify areas of research in which these nutrients affect bone
      metabolism and skeletal health.

PMID- 15159256
TI  - Evidence for potential mechanisms for the effect of conjugated linoleic acid on
      tumor metabolism and immune function: lessons from n-3 fatty acids.
AB  - Conjugated linoleic acid (CLA) and the long-chain polyunsaturated n-3 fatty acids
      have been shown in vivo and in vitro to reduce tumor growth. Tumor growth could
      occur by slowing or stopping cell replication (by interfering with transition
      through the cell cycle), increasing cell death (via necrosis and/or apoptosis),
      or both. The anticancer effects of fatty acids, shown in vivo, could also be
      mediated by effects on the host's immune system. Although it is widely recognized
      that n-3 fatty acids can alter immune and inflammatory responses, considerably
      less is known about CLA. For n-3 fatty acids, several candidate mechanisms have
      been proposed for their immune effects, including changes in 1) membrane
      structure and composition, 2) membrane-mediated functions and signals (eg,
      proteins, eicosanoids), 3) gene expression, and 4) immune development.
      Considerable work has been done that shows the potential importance of CLA as an
      anticancer treatment; however, many questions remain as to how this effect
      occurs. This review summarizes the CLA and cancer literature and then uses the
      evidence for the anticancer immune and tumor properties of the long-chain n-3
      fatty acids docosahexaenoic and eicosapentaenoic acids to suggest future research
      directions for mechanistic studies on CLA and cancer.

PMID- 15159255
TI  - Conjugated linoleic acid reduces parathyroid hormone in health and in polycystic
      kidney disease in rats.
AB  - BACKGROUND: Feeding conjugated linoleic acid (CLA) is reported to reduce
      prostaglandin E(2) synthesis, which is required for parathyroid hormone (PTH)
      release. OBJECTIVE: This study was undertaken to determine whether CLA would
      suppress hyperparathyroidism and the resulting high-turnover bone disease in a
      rat model of polycystic kidney disease (PKD). DESIGN: Outcome measurements were
      conducted after 8 wk of feeding diets supplemented with and without CLA (1% of
      dietary fat) to Han:SPRD-cy male rats (n = 52). PTH, bone formation, and
      resorption were assessed in addition to femur bone mass with use of dual-energy X
      ray absorptiometry. RESULTS: CLA feeding resulted in attenuation of PTH
      concentrations in both PKD-affected and nonaffected rats (by 60%) but did not
      significantly alter bone formation and resorption. CONCLUSION: Reduction in PTH
      may open possibilities for CLA as an adjunctive therapy in secondary
      hyperparathyroidism.

PMID- 15159257
TI  - Immunomodulatory properties of conjugated linoleic acid.
AB  - In vitro studies of the use of immune cells and animal models demonstrate that
      conjugated linoleic acid (CLA), a lipid, modulates immune function. In addition,
      recent publications demonstrate that 2 active CLA isomers (ie, cis-9,trans-11 CLA
      and trans-10,cis-12 CLA) modulate immune function in humans. Aspects of both the
      innate and adaptive immune responses are affected by dietary CLA supplementation.
      CLA consists of a mixture of isomers, which reduced immune-induced wasting and
      enhanced ex vivo lymphocyte proliferation in broilers and decreased tumor
      necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production in rat
      models. In mice, ex vivo lymphocyte proliferation and IL-2 production were
      increased. Furthermore, evidence suggests that the cis-9,trans-11 and trans
      10,cis-12 CLA isomers exert distinct effects on immune function. Specifically,
      these 2 isomers have differential effects on specific T cell populations and
      immunoglobulin subclasses in animal and human studies. Herein, a systematic
      review of the literature and relevant new data are presented with an aim to
      compare data and to present an overview covering the innate and adaptive
      components of the immune response that are regulated by CLA. In addition,
      potential mechanisms of action are discussed and the need for future studies on
      the immunomodulatory properties of CLA are outlined in detail. The understanding
      of the mechanism(s) by which CLA increases immune function will aid in the
      development of nutritionally based therapeutic applications to augment host
      resistance against infectious diseases and to treat immune imbalances, which
      result in inflammatory disorders, allergic reactions, or both.

PMID- 15159258
TI  - Conjugated linoleic acid-enriched beef production.
AB  - Canadian beef consumption is approximately 31 kg per annum, or a third of all
      meats consumed. Beef is a nutrient-rich food, providing good quality protein,
      vitamins B-6 and B-12, niacin, iron, and zinc. However, animal fats have gained
      the reputation of being less healthy. The identification of the anticarcinogenic
      effects of beef extracts due to the presence of conjugated linoleic acid (CLA)
      has heightened interest in increasing the amount of CLA deposited in beef. Beef
      cattle produce CLA and deposit these compounds in the meat; thus, beef consumers
      can receive bioformed CLA. Beef contains both of the bioactive CLA isomers,
      namely, cis-9, trans-11 and trans-10, cis-12. The relative content of these CLA
      isomers in beef depends on the feeds consumed by the animals during production.
      Feeding cattle linoleic acid-rich oils for extended periods of time increases the
      CLA content of beef. Depending on the type and relative maturity of the pasture,
      beef from pasture-fed cattle may have a higher CLA content than beef from grain-
      or silage-fed cattle. In feedlot animals fed high-grain diets, inclusion of
      dietary oil along with hay during both the growth and finishing phases led to an
      increase in CLA content from 2.8 to 14 mg/g beef fat, which would provide 77 mg
      CLA in an 85-g serving of beef. The CLAs appear to be concentrated in
      intramuscular and subcutaneous fat of beef cattle, with the CLA trans-10, cis-12
      isomer being greater in the subcutaneous fat.

PMID- 15159259
TI  - Conjugated linoleic acid pork research.
AB  - The driving force behind most conjugated linoleic acid (CLA) research in swine
      has been related to potential improvements in animal production. Early work that
      used rodent models indicated that feeding CLA could potentially reduce body fat,
      increase lean content, increase growth rate, and improve feed conversion
      efficiency. Producer-backed funding organizations were, therefore, receptive to
      proposals to extend this research to pigs, and many studies have been completed
      worldwide. In general, improvements in body composition were found, but evidence
      indicating that CLA improves growth rate or feed conversion was limited.
      Inclusion of CLA into pig diets was, however, shown to increase muscle marbling
      fat and fat hardness, and both of these characteristics have the potential to
      increase carcass value. Currently, Badische Anilin- & Soda-Fabrik AG (BASF) has
      the international marketing license to include synthetic CLA in animal feeds, but
      to date this practice is not approved in Canada or the United States. If and when
      approval is granted, the next step in realizing CLA's economic potential would be
      to seek approval for claiming CLA enrichment in pork and pork products. Given the
      ability of swine to accumulate relatively high amounts of CLA in their tissues,
      pork and pork products could become an important vehicle for delivery of
      physiologically significant amounts of CLA to consumers.

PMID- 15159260
TI  - Regulatory issues related to functional foods and natural health products in
      Canada: possible implications for manufacturers of conjugated linoleic acid.
AB  - The Canadian Food and Drugs Act and Regulations, through its definitions of food
      and drug, currently restricts health-related claims for foods, food ingredients,
      and natural health products (NHPs). Over the past few decades, scientific
      research has led to a large body of information that demonstrates the benefits
      for health of many food and NHP ingredients. Health Canada recognized the
      constraints of the current regulatory environment and started to develop
      regulations related to the allowance of health claims for functional foods and
      NHPs, including those foods and NHPs that would contain conjugated linoleic acid
      isomers. Health Canada has 3 initiatives under way in the area of health claims
      for foods: 1) to adopt the generic health claims of the United States within a
      Canadian context, 2) to develop scientific standards of evidence and a guidance
      document for supporting the validity of product-specific claims, and 3) to
      develop an overall regulatory framework for functional foods. In 2000, Health
      Canada announced approval for the use of 5 generic diet-related health claims:
      sodium and hypertension, calcium and osteoporosis, saturated and trans fat and
      cholesterol and coronary artery disease, fruits and vegetables and cancer, and
      sugar alcohols and dental caries. Under a separate initiative, Natural Health
      Products Regulations were published in the Canada Gazette Part II on June 18,
      2003. The NHP Regulations came into force on January 1, 2004, with a transition
      period ranging from 2 y (for site licensing) to 6 y (for product licensing, for
      products already issued a drug identification number).

PMID- 15159261
TI  - Osteoporosis screening: time to take responsibility.

PMID- 15159262
TI  - Acute mesenteric ischemia: a clinical review.
AB  - Acute mesenteric ischemia is a life-threatening vascular emergency that requires
      early diagnosis and intervention to adequately restore mesenteric blood flow and
      to prevent bowel necrosis and patient death. The underlying cause is varied, and
      the prognosis depends on the precise pathologic findings. Despite the progress in
      understanding the pathogenesis of mesenteric ischemia and the development of
      modern treatment modalities, acute mesenteric ischemia remains a diagnostic
      challenge for clinicians, and the delay in diagnosis contributes to the continued
      high mortality rate. Early diagnosis and prompt effective treatment are essential
      to improve the clinical outcome.

PMID- 15159263
TI  - Prevalence of the metabolic syndrome and its relation to all-cause and
      cardiovascular mortality in nondiabetic European men and women.
AB  - BACKGROUND: Few studies have evaluated the associations between the metabolic
      syndrome (by any definition) and mortality. This study examined the age- and sex
      specific prevalence of the metabolic syndrome and its association with all-cause
      and cardiovascular mortality in nondiabetic European men and women. METHODS: The
      study was based on 11 prospective European cohort studies comprising 6156 men and
      5356 women without diabetes and aged from 30 to 89 years, and had a median follow
      up of 8.8 years. A modification of the World Health Organization definition of
      the metabolic syndrome was used. The subjects were considered to have the
      metabolic syndrome if they had hyperinsulinemia and 2 or more of the following:
      obesity, hypertension, dyslipidemia, or impaired glucose regulation; however,
      other definitions were also studied. Hazard ratios for all-cause and
      cardiovascular mortality were estimated with Cox models in each cohort. Meta
      analyses were performed to assess the overall association of the metabolic
      syndrome with mortality risk. RESULTS: The age-standardized prevalence of the
      metabolic syndrome was slightly higher in men (15.7%) than in women (14.2%). Of
      the 1119 deaths recorded during follow-up, 432 were caused by cardiovascular
      disease. The overall hazard ratios for all-cause and cardiovascular mortality in
      persons with the metabolic syndrome compared with persons without it were 1.44
      (95% confidence interval [CI], 1.17-1.84) and 2.26 (95% CI, 1.61-3.17) in men and
      1.38 (95% CI, 1.02-1.87) and 2.78 (95% CI, 1.57-4.94) in women after adjustment
      for age, blood cholesterol levels, and smoking. CONCLUSIONS: The overall
      prevalence of the metabolic syndrome in nondiabetic adult Europeans is 15%.
      Nondiabetic persons with the metabolic syndrome have an increased risk of death
      from all causes as well as cardiovascular disease.

PMID- 15159264
TI  - Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular
      weight heparin in the initial treatment of venous thromboembolism.
AB  - BACKGROUND: Few reports have addressed the value of unfractionated heparin (UFH)
      or low-molecular-weight heparin in treating the full spectrum of patients with
      venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism.
      METHODS: In an open, multicenter clinical trial, 720 consecutive patients with
      acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with
      pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to
      treatment with subcutaneous UFH with dose adjusted by activated partial
      thromboplastin time by means of a weight-based algorithm (preceded by an
      intravenous loading dose), or fixed-dose (adjusted only to body weight)
      subcutaneous nadroparin calcium. Oral anticoagulant therapy was started
      concomitantly and continued for at least 3 months. We recorded the incidence of
      major bleeding during the initial heparin treatment and that of recurrent VTE and
      death during 3 months of follow-up. RESULTS: Fifteen (4.2%) of the 360 patients
      assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%)
      of the 360 patients assigned to nadroparin (absolute difference between rates,
      0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH
      (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major
      bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2%
      to 1.7%). Overall mortality was 3.3% in each group. CONCLUSIONS: Subcutaneous UFH
      with dose adjusted by activated partial thromboplastin time by means of a weight
      based algorithm is as effective and safe as fixed-dose nadroparin for the initial
      treatment of patients with VTE, including those with pulmonary embolism and
      recurrent VTE.

PMID- 15159265
TI  - Benefits of 2 years of intense exercise on bone density, physical fitness, and
      blood lipids in early postmenopausal osteopenic women: results of the Erlangen
      Fitness Osteoporosis Prevention Study (EFOPS).
AB  - BACKGROUND: Growing evidence indicates that physical exercise can prevent at
      least some of the negative effects on health associated with early menopause.
      Here we determine the effects of intense exercise on physical fitness, bone
      mineral density (BMD), back pain, and blood lipids in early postmenopausal women.
      METHODS: The study population comprised 50 fully compliant women, with no
      medication or illness affecting bone metabolism, who exercised over 26 months
      (exercise group [EG]), and 33 women who served as a nontraining control group
      (CG). Two group training sessions per week and 2 home training sessions per week
      were performed in the EG. Both groups were individually supplemented with calcium
      and cholecalciferol. Physical fitness was determined by maximum strength and
      cardiovascular performance. Bone mineral density was measured at the lumbar spine
      (dual-energy x-ray absorptiometry [DXA] and quantitative computed tomography
      [QCT]), the proximal femur (DXA), and the forearm (DXA). In serum samples taken
      from a subset of the study participants, we determined bone formation (serum
      osteocalcin) and resorption (serum cross-links) markers as well as blood lipid
      levels. Vasomotor symptoms related to menopause and pain were also assessed.
      RESULTS: After 26 months, significant exercise effects determined as percentage
      changes compared with baseline were observed for physical fitness (isometric
      strength: trunk extensors [EG +36.5% vs CG +1.7%], trunk flexors [EG +39.3% vs CG
      -0.4%], and maximum oxygen consumption [EG +12.4% vs CG -2.3%]); BMD (lumbar
      spine [DXA L1-L4, EG +0.7% vs CG -2.3%], QCT L1-L3 trabecular region of interest
      [EG +0.4% vs CG -6.6%], QCT L1-L3 cortical region of interest [EG +3.1% vs CG 
      1.7%], and total hip [DXA, EG -0.3% vs CG -1.7%]); serum levels (total
      cholesterol [EG -5.0% vs CG +4.1%] and triglycerides [EG -14.2% vs CG +23.2%]);
      and pain indexes at the spine. CONCLUSION: General purpose exercise programs with
      special emphasis on bone density can significantly improve strength and endurance
      and reduce bone loss, back pain, and lipid levels in osteopenic women in their
      critical early postmenopausal years.

PMID- 15159266
TI  - Cardiorespiratory fitness attenuates the effects of the metabolic syndrome on all
      cause and cardiovascular disease mortality in men.
AB  - BACKGROUND: The metabolic syndrome is a prevalent condition that carries with it
      an increased risk of type 2 diabetes mellitus, cardiovascular disease (CVD), and
      mortality. OBJECTIVE: To determine the relationship between cardiorespiratory
      fitness (CRF) and mortality in healthy men and in those with the metabolic
      syndrome. METHODS: The sample included 19 223 men, aged 20 to 83 years, who
      received a clinical evaluation between 1979 and 1995 with mortality follow-up
      through December 31, 1996. There were 15 466 healthy men (80.5%) and 3757 men
      with the metabolic syndrome (19.5%). RESULTS: A total of 480 deaths (161 due to
      CVD) occurred during 196 298 man-years of follow-up. After adjustment for age,
      year of examination, smoking status, alcohol consumption, and parental CVD, the
      relative risks (RRs) (95% confidence interval) of all-cause and CVD mortality
      were 1.29 (1.05-1.57) and 1.89 (1.36-2.60), respectively, for men with the
      metabolic syndrome compared with healthy men. After the inclusion of CRF, the
      associations were not significant. The RRs comparing unfit with fit men for all
      cause mortality were 2.18 (1.66-2.87) in healthy men and 2.01 (1.38-2.93) in men
      with the metabolic syndrome, whereas the RRs for CVD mortality for unfit vs fit
      men were 3.21 (2.03-5.07) in healthy men and 2.25 (1.27-3.97) in men with the
      metabolic syndrome. A significant dose-response relationship between CRF and
      mortality was also observed in men with the metabolic syndrome. CONCLUSION: In
      this sample, CRF provided a strong protective effect against all-cause and CVD
      mortality in healthy men and men with the metabolic syndrome.

PMID- 15159267
TI  - Disability and chronic fatigue syndrome: a focus on function.
AB  - BACKGROUND: Evidence was sought in the published literature on how best to
      measure, monitor, and treat disability in patients with chronic fatigue syndrome
      (CFS). METHODS: A systematic review was performed of English-language literature
      published between January 1, 1988, and November 15, 2001. Interventional and
      observational studies of adults with CFS were eligible if they reported measures
      of disability and employment. A qualitative synthesis of results relating
      impairment measures to employment was performed. RESULTS: Of 3840 studies
      identified, 37 reported employment status and some measure of mental or physical
      impairment associated with disability. Most patients with CFS in these studies
      were unemployed. In 22 studies, the employment status of control subjects was
      also available. Only depression seemed to be associated with unemployment in
      patients with CFS. No other measurable impairment seemed to be consistently
      associated with disability or work outcomes. Only cognitive behavior therapy,
      rehabilitation, and exercise therapy interventions were associated with restoring
      the ability to work. No specific patient characteristics were identified as best
      predictors of positive employment outcomes. No quantitative syntheses of results
      were performed. CONCLUSIONS: For questions of disability and employment in CFS,
      the limitations inherent in the current literature are extensive.
      Methodologically rigorous, longitudinal, and interventional studies are needed to
      determine baseline characteristics that are associated with the inability to work
      and interventions that are effective in restoring the ability to work in the CFS
      population. Simple and consistent evaluations of functional capacity in patients
      with CFS are needed.

PMID- 15159268
TI  - Bone mineral density thresholds for pharmacological intervention to prevent
      fractures.
AB  - BACKGROUND: Treatment intervention thresholds for prevention of osteoporotic
      fractures can be derived from reports from the World Health Organization
      (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria).
      It is not known how well these thresholds work to identify women who will
      fracture and are therefore candidates for treatment interventions. We used data
      from the National Osteoporosis Risk Assessment (NORA) to examine the effect of
      different treatment thresholds on fracture incidence and numbers of women with
      fractures within the year following bone mineral density measurement. METHODS:
      The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean
      age, 64.5 years). At baseline, bone mineral density was assessed by peripheral
      bone densitometry at the heel, finger, or forearm. New fractures during the next
      12 months were self-reported. RESULTS: New fractures were reported by 2259 women,
      including 393 hip fractures; only 6.4% had baseline T scores of -2.5 or less
      (World Health Organization definition for osteoporosis). Although fracture rates
      were highest in these women, they experienced only 18% of the osteoporotic
      fractures and 26% of the hip fractures. By National Osteoporosis Foundation
      treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or -1.5 or
      less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of
      osteoporotic fractures and 53% of hip fractures occurred in these women.
      CONCLUSIONS: Using peripheral measurement devices, 82% of postmenopausal women
      with fractures had T scores better than -2.5. A strategy to reduce overall
      fracture incidence will likely require lifestyle changes and a targeted effort to
      identify and develop treatment protocols for women with less severe low bone mass
      who are nonetheless at increased risk for future fractures.

PMID- 15159269
TI  - An approach to identifying osteopenic women at increased short-term risk of
      fracture.
AB  - BACKGROUND: Identification and management of women to reduce fractures is often
      limited to T scores less than -2.5, although many fractures occur with higher T
      scores. We developed a classification algorithm that identifies women with
      osteopenia (T scores of -2.5 to -1.0) who are at increased risk of fracture
      within 12 months of peripheral bone density testing. METHODS: A total of 57 421
      postmenopausal white women with baseline peripheral T scores of -2.5 to -1.0 and
      1-year information on new fractures were included. Thirty-two risk factors for
      fracture were entered into a classification and regression tree analysis to build
      an algorithm that best predicted future fracture events. RESULTS: A total of 1130
      women had new fractures in 1 year. Previous fracture, T score at a peripheral
      site of -1.8 or less, self-rated poor health status, and poor mobility were
      identified as the most important determinants of short-term fracture. Fifty-five
      percent of the women were identified as being at increased fracture risk. Women
      with previous fracture, regardless of T score, had a risk of 4.1%, followed by
      2.2% in women with T scores of -1.8 or less or with poor health status, and 1.9%
      for women with poor mobility. The algorithm correctly classified 74% of the women
      who experienced a fracture. CONCLUSIONS: This classification tool accurately
      identified postmenopausal women with peripheral T scores of -2.5 to -1.0 who are
      at increased risk of fracture within 12 months. It can be used in clinical
      practice to guide assessment and treatment decisions.

PMID- 15159270
TI  - Efficacy of extended-release niacin with lovastatin for hypercholesterolemia:
      assessing all reasonable doses with innovative surface graph analysis.
AB  - BACKGROUND: Combination therapy to improve the total lipid profile may achieve
      greater coronary risk reductions than lowering low-density lipoprotein
      cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin
      tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and
      raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these
      serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses.
      METHODS: Men (n = 85) and women (n = 79) with type IIa or IIb primary
      hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each
      arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d,
      increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg,
      increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant
      lovastatin dose and escalating niacin ER doses. RESULTS: For primary comparisons,
      mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin
      (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%, P<.001) and with niacin
      ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%, P<.001).
      Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an
      additional 4% and increased HDL-C levels 8%. The maximum recommended dose
      (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%,
      triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were
      dose dependent and generally additive. Graphs of the dose-response relationships
      as 3-dimensional surfaces documented the strength and consistency of these
      responses. CONCLUSIONS: Niacin ER/lovastatin combination therapy substantially
      improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose
      response surfaces provide a practical guide for dose selection.

PMID- 15159271
TI  - Socioeconomic status and outcome following acute myocardial infarction in elderly
      patients.
AB  - BACKGROUND: Although the Medicare entitlement provides universal hospital care
      coverage for elderly Americans, disparities in care processes after acute
      myocardial infarction still exist. Whether these disparities account for
      increased mortality among elderly poor patients is not known. METHODS: To
      determine the association between socioeconomic status and acute myocardial
      infarction treatment, procedure use, and 30-day and 1-year mortality, we analyzed
      data from 132 130 elderly Medicare beneficiaries hospitalized for acute
      myocardial infarction between January 1994 and February 1996. Patients were
      categorized into 10 groups of increasing income using the median income of the
      ZIP code of residence. RESULTS: The highest-income beneficiaries received higher
      rates of evidence-based medical therapy and had lower adjusted 30-day and 1-year
      mortality rates compared with the middle-income beneficiaries (30-day relative
      risk, 0.89 [95% confidence interval, 0.85-0.94]; and 1-year relative risk, 0.92
      [95% confidence interval, 0.88-0.97]). Conversely, the lowest-income
      beneficiaries received lower rates of evidence-based medical treatment and had
      higher adjusted 30-day and 1-year mortality rates relative to the middle-income
      beneficiaries (30-day relative risk, 1.09 [95% confidence interval, 1.04-1.13];
      and 1-year relative risk, 1.05 [95% confidence interval, 1.00-1.10]). Coronary
      revascularization rates were similar among income groups. CONCLUSIONS: Despite
      the Medicare entitlement, there remain significant socioeconomic disparities in
      medical treatment and mortality among elderly patients following acute myocardial
      infarction. Income was independently associated with short- and long-term
      mortality. More research is required to determine the mechanisms contributing to
      adverse outcomes among poor elderly patients and to determine whether expansion
      of Medicare coverage will alleviate these disparities.

PMID- 15159272
TI  - Trends in complexity of diabetes care in the United States from 1991 to 2000.
AB  - BACKGROUND: During the decade from 1991 to 2000, the standard of care for
      diabetes mellitus evolved to require more intensive management of glycemia, blood
      pressure, and cholesterol levels. METHODS: To assess changes in the complexity of
      outpatient management of diabetes, we used nationally representative data from
      the National Ambulatory Medical Care Survey. For 4708 primary care visits by
      patients with diabetes from 1991 to 2000, we characterized trends in the number
      of prescribed medicines, management of hyperglycemia, hypertension, and
      hyperlipidemia, provision of diabetes-related ambulatory services, and visit
      length. RESULTS: From 1991 to 2000, the annual proportion of primary care visits
      listing at least 5 prescription medicines increased from 18.2% to 29.9% (P<.001).
      We found increases in visits listing oral medications for control of glucose
      levels (37.2% to 50.5%; P<.001), antihypertensive agents (35.9% to 42.3%;
      P<.001), and medications for lowering of lipid levels (4.1% to 17.3%; P<.001),
      whereas visits listing insulin treatment decreased from 25.3% in 1991 to 15.3% in
      2000 (P<.001). Provision of diabetes-related ambulatory services remained stable
      (blood pressure measurement, cholesterol level testing, and dietary and smoking
      cessation counseling) or increased (exercise counseling; P =.01). The proportion
      of visits longer than 20 minutes increased from 17.8% in 1991 to 20.9% in 2000 (P
      =.02 for trend). CONCLUSIONS: Office-based management of diabetes has changed
      significantly during the study decade. We found a marked increase in medical
      regimen complexity, a modest increase in visit length, and stable or increased
      provision of diabetes-related screening and counseling services. The increasing
      complexity of medical care combined with limited time during clinic visits may
      represent a barrier to achieving evidence-based goals of diabetes care.

PMID- 15159273
TI  - The association between obesity and screening mammography accuracy.
AB  - BACKGROUND: Obesity is increasing among American women, especially as they age.
      The influence of obesity on the accuracy of screening mammography has not been
      studied extensively. METHODS: We analyzed 100 622 screening mammography
      examinations performed on members of a nonprofit health plan. The relationship
      between body mass index (weight in kilograms divided by the square of height in
      meters) and measures of screening accuracy was assessed. Body mass index was
      categorized as underweight or normal weight (<25), overweight (25-29), obesity
      class I (30-34), and obesity classes II to III (> or =35). RESULTS: Compared with
      underweight or normal weight women, overweight and obese women were more likely
      to be recalled for additional tests after adjusting for important covariates,
      including age and breast density (overweight odds ratio [OR], 1.17; 95%
      confidence interval [CI], 1.11-1.23); obesity class I OR, 1.27; 95% CI, 1.19
      1.35; obesity classes II-III OR, 1.31; 95% CI, 1.22-1.41). As body mass index
      increased, women were more likely to have lower specificity (overweight OR, 0.86;
      95% CI, 0.81-0.90; obesity class I OR, 0.79; 95% CI, 0.74-0.84; and obesity
      classes II-III OR, 0.77; 95% CI, 0.71-0.82). No statistically significant
      differences were noted in sensitivity. Adjusted receiver operating characteristic
      analysis showed statistically significant improvement in the area under the curve
      (AUC) for underweight or normal weight women (AUC = 0.941) vs overweight women
      (AUC = 0.916, P =.02) and underweight or normal weight women vs obesity classes
      II and III women (AUC = 0.904, P =.02). CONCLUSIONS: Obese women had more than a
      20% increased risk of having false-positive mammography results compared with
      underweight and normal weight women, although sensitivity was unchanged.
      Achieving a normal weight may improve screening mammography performance.

PMID- 15159274
TI  - Fatal mesenteric fibromuscular dysplasia: a case report and review of the
      literature.
AB  - Fibromuscular dysplasia is a rare nonatherosclerotic, noninflammatory angiopathy
      of uncertain etiology and high morbidity. Because of its propensity to affect
      medium-sized vessels in a variety of locations, presenting symptoms may vary
      substantially, resulting in a delayed or missed diagnosis. We describe a 57-year
      old woman who, on multiple occasions, presented with progressive gastrointestinal
      symptoms and eventually underwent surgical revascularization for celiac and
      superior mesenteric artery stenosis of uncertain etiology. Her postoperative
      course was complicated by bowel ischemia, multiple organ failure, and death.
      Autopsy findings proved useful in determining the underlying disease process and
      cause of death. This case report and a review of the literature illustrate the
      high morbidity and mortality that are caused by mesenteric fibromuscular
      dysplasia, the challenge in establishing a correct diagnosis, and the importance
      of early detection and treatment.

PMID- 15159275
TI  - Auranofin induces apoptosis and when combined with retinoic acid enhances
      differentiation of acute promyelocytic leukaemia cells in vitro.
AB  - 1. Acute promyelocytic leukaemia (APL) is characterized by a block in
      differentiation at the promyelocyte stage. Here, we describe the effects of
      auranofin (AF), a coordinated gold compound, on apoptosis and differentiation of
      APL cells. 2. Nucleosomal DNA fragmentation assay and Hoechst 33342 staining
      indicated that AF induced apoptosis in APL-derived NB4 cells at low
      concentrations (0.5-1.0 microm). The AF-induced apoptosis involved caspase-3
      activation and specific cleavage of poly-ADP-ribose polymerase. 3. The AF-treated
      NB4 cells also produced reactive oxygen species (ROS) and cotreatment with N
      acetyl-l-cysteine protected the NB4 cells from AF-induced apoptosis. 4.
      Expression of the CD11b cell surface marker and C/EBPepsilon was increased when
      the cells were treated for 4 days with 0.3 microm AF and a physiological
      concentration of all-trans retinoic acid (ATRA, 5 nm). Treatment with AF in
      combination with ATRA markedly increased the number of cells with differentiated
      features, such as lobed or multiple nuclei and numerous granules and vacuoles. At
      these low concentrations, neither AF nor ATRA alone induced significant cell
      differentiation. 5. These findings suggest not only that AF induces caspase-3
      dependent apoptosis via a mechanism involving ROS, but also that the combined
      treatment with AF and ATRA induces differentiation of NB4 cells. Our results
      demonstrate a novel characteristic of AF from which an effective drug treatment
      of APL might be developed.

PMID- 15159276
TI  - Alpha-1D adrenoceptors are involved in reserpine-induced supersensitivity of rat
      tail artery.
AB  - 1. We examined reserpine-induced chemical denervation supersensitivity with
      special reference to alpha-1 adrenoceptor (AR) subtypes. 2. Chronic treatment
      with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen
      of rats. Noradrenaline in the thoracic aorta was negligible before and after
      reserpine treatment. 3. The treatment with reserpine produced supersensitivity in
      the contractile responses of the rat tail artery to phenylephrine, 5-HT and KCl,
      resulting in leftward shift of concentration-response curves (11.6-, 2.5- and 1.1
      fold at EC(50) value, respectively). These results suggest a predominant
      sensitization of the alpha-1 AR-mediated response by reserpine treatment. 4. BMY
      7378 at a concentration (30 nm) specific for blocking the alpha-1D AR subtype,
      but not KMD-3213 at a concentration (10 nm) selective for blocking the alpha-1A
      AR subtype, inhibited the supersensitivity of the phenylephrine-induced response
      in the reserpine-treated artery. On the other hand, the response to phenylephrine
      in reserpine-untreated artery was selectively inhibited by the same concentration
      of KMD-3213, but not by BMY 7378. Prazosin, a subtype-nonselective antagonist,
      blocked the responses to phenylephrine with the same potency, regardless of
      reserpine treatment. 5. In the thoracic aorta and spleen, no supersensitivity was
      produced in the responses to phenylephrine by reserpine treatment. 6. In a tissue
      segment-binding study using [(3)H]-prazosin, the total density and affinity of
      alpha-1 ARs in the rat tail artery were not changed by treatment with reserpine.
      However, alpha-1D AR with high affinity for BMY 7378 was significantly detected
      in reserpine-treated tail artery, in contrast to untreated artery. Decreases in
      alpha-1A AR with high affinity for KMD-3213 and alpha-1B AR with low affinities
      for KMD-3213 and BMY 7378 were also estimated in reserpine-treated tail artery.
      7. Alpha-1D AR mRNA in rat tail artery increased to three-folds by reserpine
      treatment, whereas the levels of alpha-1A and 1B mRNAs were not significantly
      changed. 8. The present results suggest that chronic treatment with reserpine
      affects the expression of alpha-1 AR subtypes of rat tail artery and that the
      induction of alpha-1D ARs with high affinity for catecholamines is in part
      associated with reserpine-induced supersensitivity.

PMID- 15159277
TI  - Comparative anti-inflammatory activities of antagonists to C3a and C5a receptors
      in a rat model of intestinal ischaemia/reperfusion injury.
AB  - 1. Complement activation is implicated in the pathogenesis of intestinal
      ischaemia-reperfusion injury (I/R), although the relative importance of
      individual complement components is unclear. A C3a receptor antagonist N(2)-[(2,2
      diphenylethoxy)acetyl]-l-arginine (C3aRA) has been compared with a C5a receptor
      antagonist (C5aRA), AcF-[OPdChaWR], in a rat model of intestinal I/R. 2. C3aRA
      (IC(50)=0.15 microm) and C5aRA (IC(50)=0.32 microm) bound selectively to human
      polymorphonuclear leukocyte (PMN) C3a and C5a receptors, respectively. Effects on
      circulating neutrophils and blood pressure in the rat were also assessed. 3.
      Anaesthetised rats, subjected to intestinal ischaemia (30 min) and reperfusion
      (120 min), were administered intravenously with either (A) the C3aRA (0.1-1.0 mg
      x kg(-1)); the C5aRA (1.0 mg x kg(-1)); the C3aRA+C5aRA (each 1.0 mg x kg(-1));
      or vehicle, 45 min prior, or (B) the C3aRA (1.0 mg x kg(-1)) or vehicle, 120 min
      prior to reperfusion. 4. The C3aRA and C5aRA, administered 45 min prior to
      reperfusion, displayed similar efficacies at ameliorating several disease markers
      (increased oedema, elevated ALT levels and mucosal damage) of rat intestinal I/R.
      The combination drug treatment did not result in greater injury reduction than
      either antagonist alone. However, doses of the C3aRA (0.01-10 mg x kg(-1)) caused
      transient neutropaenia, and the highest dose (10 mg x kg(-1)) also caused a rapid
      and transient hypertension. 5. The C3aRA (1.0 mg x kg(-1)), delivered 120 min
      prior to reperfusion to remove the global effect of C3aRA-induced neutrophil
      sequestration, did not attenuate the markers of intestinal I/R, despite
      persistent C3aR antagonism at this time. 6. C3aR antagonism does not appear to be
      responsible for the anti-inflammatory actions of this C3aRA in intestinal I/R in
      the rat. Instead, C3aRA-mediated global neutrophil tissue sequestration during
      ischaemia and early reperfusion may account for the protective effects observed.

PMID- 15159279
TI  - Attenuation of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced
      rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists.
AB  - 1. Studies were designed to examine the effects of alpha(1) (alpha(1)AR)- plus
      beta(3)-adrenoreceptor (beta(3)AR) antagonists on 3,4
      methylenedioxymethamphetamine (MDMA, Ecstasy)-induced hyperthermia and measures
      of rhabdomyolysis (creatine kinase (CK)) and renal function (blood urea nitrogen
      (BUN) and serum creatinine (sCr)) in male Sprague-Dawley rats. 2. MDMA (40 mg x
      kg(-1), s.c.) induced a rapid and robust increase in rectal temperature, which
      was significantly attenuated by pretreatment with the alpha(1)AR antagonist
      prazosin (100 microg x kg(-1), i.p.) plus the beta(3)AR antagonist SR59230A (5 mg
      x kg(-1), i.p.). 3. CK levels significantly increased (peaking at 4 h) after MDMA
      treatment and were blocked by the combination of prazosin plus SR59230A. 4. At 4
      h after MDMA treatment, BUN and sCr levels were also significantly increased and
      could be prevented by this combination of alpha(1)AR- plus beta(3)AR-antagonists.
      5. The results from this study suggest that alpha(1)AR and beta(3)AR play a
      critical role in the etiology of MDMA-mediated hyperthermia and subsequent
      rhabdomyolysis.

PMID- 15159278
TI  - Mechanisms involved in carbachol-induced Ca(2+) sensitization of contractile
      elements in rat proximal and distal colon.
AB  - 1. Mechanisms involved in Ca(2+) sensitization of contractile elements induced by
      the activation of muscarinic receptors in membrane-permeabilized preparations of
      the rat proximal and distal colon were studied. 2. In alpha-toxin-permeabilized
      preparations from the rat proximal and distal colon, Ca(2+) induced a rapid
      phasic and subsequent tonic component. After Ca(2+)-induced contraction reached a
      plateau, guanosine 5'-triphosphate (GTP) and carbachol (CCh) in the presence of
      GTP further contracted preparations of both the proximal and distal colon (Ca(2+)
      sensitization). Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced
      Ca(2+) sensitization more significantly in the proximal colon than in the distal
      colon. 3. Y-27632 at 10 microm had no effect on Ca(2+)-induced contraction or
      slightly inhibited phorbol-12,13-dibutyrate-induced Ca(2+) sensitization in
      either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor,
      inhibited GTP plus CCh-induced Ca(2+) sensitization in the distal colon, but not
      in the proximal colon. The component of Ca(2+) sensitization that persisted after
      the chelerythrine treatment was completely inhibited by Y-27632. 4. In beta-escin
      permeabilized preparations of the proximal colon, C3 exoenzyme completely
      inhibited GTP plus CCh-induced Ca(2+) sensitization, but PKC(19-31) did not. In
      the distal colon, C3 exoenzyme abolished GTP-induced Ca(2+) sensitization. It
      inhibited CCh-induced sensitization by 50 % and the remaining component was
      inhibited by PKC(19-31). 5. These results suggest that both protein kinase C and
      rho pathways in parallel mediate the Ca(2+) sensitization coupled to activation
      of muscarinic receptors in the rat distal colon, whereas the rho pathway alone
      mediates this action in the proximal colon.

PMID- 15159280
TI  - Upregulation of orphan nuclear receptor Nur77 following PGF(2alpha), Bimatoprost,
      and Butaprost treatments. Essential role of a protein kinase C pathway involved
      in EP(2) receptor activated Nur77 gene transcription.
AB  - 1. Using gene chip technology, we first identified that PGF(2alpha) (FP agonist)
      and Butaprost (EP(2) agonist) induced about a five-fold upregulation of Nur77
      mRNA expression in hFP-HEK 293/EBNA and hEP(2)-HEK293/EBNA cells. Northern Blot
      analysis revealed that PGF(2alpha)- and Butaprost-induced upregulation of Nur77
      expression are dose- and time-dependent. 2. Both PGF(2alpha) and Butaprost
      upregulated Nur77 gene expression through the protein kinase C (PKC) pathway.
      These data are the first showing a link between EP(2) receptor stimulation and
      protein kinase C activation. Calcineurin was found to be involved downstream of
      the PKC pathway in PGF(2alpha)-induced Nur77 expression, but not in Butaprost
      induced Nur77 expression. 3. We also used Nur77 as a marker gene to compare the
      effects of PGF(2alpha), Butaprost, and Bimatoprost (a prostamide) on Nur77
      expression in human primary trabecular meshwork and ciliary smooth muscle (SM)
      cells, which are target cells for antiglaucoma drugs. The results showed that
      PGF(2alpha) and Butaprost, but not Bimatoprost, induced upregulation of Nur77
      expression in human TM cells. PGF(2alpha), but not Bimatoprost, dramatically
      induced upregulation of Nur77 mRNA expression in human ciliary SM cells, whereas
      Butaprost slightly upregulated Nur77 mRNA expression in SM cells. 4. Nur77
      promoter deletion analysis indicated that PGF(2alpha), but not Bimatoprost,
      activated Nur77 promoter-luciferase reporter in hFP-HEK 293/EBNA cells. Butaprost
      was less efficacious in inducing Nur77 promoter-luciferase reporter activity in
      hEP(2)-HEK293/EBNA cells relative to PGF(2alpha) in the comparable assay. The
      data for Nur77 promoter functional analysis were matched to the Northern blot
      analysis. 5. It appears that PGF(2alpha) and Butaprost activate Nur77
      transcription mechanisms through the activation of FP and EP(2) receptor-coupled
      signaling pathways, whereas Bimatoprost stimulates neither FP nor EP(2)
      receptors.

PMID- 15159281
TI  - Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct
      size in rats: involvement of nitric oxide.
AB  - 1. The effects of short-term oral administration of red wine polyphenolic
      compounds (RWPC, 20 mg x kg(-1) day(-1) for 7 days) on haemodynamics, ex vivo
      cardiac responsiveness and ischaemia-reperfusion injury were investigated in
      rats. The involvement of nitric oxide (NO) was evaluated using the NO synthase
      inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 2 mg x kg(-1) day(-1) for
      7 days), at a dose which did not affect blood pressure. 2. Ex vivo reactivity of
      hearts from RWPC-treated rats showed lower basal developed pressure, greater
      heart rate and decreased inotropic responses to either beta-adrenoceptor or
      muscarinic receptor stimulation with isoprenaline or carbachol, respectively.3.
      RWPC treatment did not modify cardiac expression of endothelial NO synthase or
      Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary
      effluent. 4. In ischaemia-reperfusion, RWPC treatment reduced infarct size and
      oxidative stress, as shown by the myocardial content of the end products of lipid
      peroxidation, malondialdehyde and 4-hydroxynonenal, without affecting post
      ischaemic contractile dysfunction. All the observed effects of RWPC were
      prevented by l-NAME treatment. 5. Altogether, these data show that short-term
      treatment with RWPC decreases blood pressure and cardiac responsiveness, and
      protects against post-ischaemic infarction via decreased oxidative stress. All
      the above effects of RWPC are sensitive to NO synthase inhibition that implies an
      involvement of NO-dependent pathway. This study suggests a basis for the
      beneficial effects of plant-derived polyphenols against cardiovascular disease.

PMID- 15159282
TI  - Acute and late effects on induction of allodynia by acromelic acid, a mushroom
      poison related structurally to kainic acid.
AB  - 1. Ingestion of a poisonous mushroom Clitocybe acromelalga is known to cause
      severe tactile pain (allodynia) in the extremities for a month and acromelic acid
      (ACRO), a kainate analogue isolated from the mushroom, produces selective damage
      of interneurons of the rat lower spinal cord when injected either systemically or
      intrathecally. Since ACRO has two isomers, ACRO-A and ACRO-B, here we examined
      their acute and late effects on induction of allodynia. 2. Intrathecal
      administration of ACRO-A and ACRO-B provoked marked allodynia by the first
      stimulus 5 min after injection, which lasted over the 50-min experimental period.
      Dose-dependency of the acute effect of ACRO-A on induction of allodynia showed a
      bell-shaped pattern from 50 ag x kg(-1) to 0.5 pg x kg(-1) and the maximum effect
      was observed at 50 fg x kg(-1). On the other hand, ACRO-B induced allodynia in a
      dose-dependent manner from 50 pg x kg(-1) to 50 ng x kg(-1). 3. N-methyl-d
      aspartate (NMDA) receptor antagonists and Joro spider toxin, a Ca(2+)-permeable
      AMPA receptor antagonist, inhibited the allodynia induced by ACRO-A, but not by
      ACRO-B. However, other AMPA/kainate antagonists did not affect the allodynia
      induced by ACRO. 4. Whereas no neuronal damage was observed in the spinal cord in
      ACRO-A-treated mice, induction of allodynia by ACRO-A (50 fg x kg(-1)) and ACRO-B
      (50 ng x kg(-1)) was selectively lost 1 week after i.t. injection of a sublethal
      dose of ACRO-A (50 ng x kg(-1)) or ACRO-B (250 ng x kg(-1)). Higher doses of ACRO
      A, however, could evoke allodynia dose-dependently from 50 pg x kg(-1) to 500 ng
      x kg(-1) in the ACRO-A-treated mice. The allodynia induced by ACRO-A (500 ng x
      kg(-1)) was not inhibited by Joro spider toxin or NMDA receptor antagonists.
      These properties of the late allodynia induced by ACRO-A were quite similar to
      those of the acute allodynia induced by ACRO-B. 5. ACRO-A could increase
      [Ca(2+)](i) in the deeper laminae, rather than in the superficial laminae, of the
      spinal cord. This increase was not blocked by the AMPA-preferring antagonist
      GYKI52466 and Joro spider toxin. 6. Taken together, these results demonstrate the
      stereospecificity of ACRO for the induction of allodynia and suggest the presence
      of a receptor specific to ACRO.

PMID- 15159283
TI  - Selectins and integrins but not platelet-endothelial cell adhesion molecule-1
      regulate opioid inhibition of inflammatory pain.
AB  - 1. Control of inflammatory pain can result from activation of opioid receptors on
      peripheral sensory nerves by opioid peptides secreted from leukocytes in response
      to stress (e.g. experimental swim stress or surgery). The extravasation of
      immunocytes to injured tissues involves rolling, adhesion and transmigration
      through the vessel wall, orchestrated by various adhesion molecules. 2. Here we
      evaluate the relative contribution of selectins, integrins alpha(4) and beta(2),
      and platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the opioid
      mediated inhibition of inflammatory pain. 3. We use flow cytometry, double
      immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral
      hind paw inflammation induced by complete Freund's adjuvant. 4. In inflamed
      tissue, 43-58% of hematopoietic cells (CD45(+)) expressed opioid peptides. L
      selectin and beta(2) were coexpressed by 7 and 98% of opioid-containing
      leukocytes, respectively. Alpha(4) integrin was expressed in low levels by the
      majority of leukocytes. Opioid-containing cells, vascular P- and E-selectin and
      PECAM-1 were simultaneously upregulated. 5. Swim stress produced potent opioid
      mediated antinociception in inflamed tissue, unaffected by blockade of PECAM-1.
      However, blockade of L- and P-selectins by fucoidin, or of alpha(4) and beta(2)
      by monoclonal antibodies completely abolished peripheral stress-induced
      antinociception. This coincided with a 40% decrease in the migration of opioid
      containing leukocytes to inflamed tissue. 6. These findings establish selectins
      and integrins alpha(4) and beta(2), but not PECAM-1, as important molecules
      involved in stress-induced opioid-mediated antinociception in inflammation. They
      point to a cautious use of anti-inflammatory treatments applying anti-selectin,
      anti-alpha(4) and anti-beta(2) strategies because they may impair intrinsic pain
      inhibition.

PMID- 15159284
TI  - Presynaptic cannabinoid CB(1) receptors are involved in the inhibition of the
      neurogenic vasopressor response during septic shock in pithed rats.
AB  - 1. Our study was undertaken to investigate whether bacterial
      endotoxin/lipopolysaccharide (LPS) affects the neurogenic vasopressor response in
      rats in vivo by presynaptic mechanisms and, if so, to characterize the type of
      presynaptic receptor(s) operating in the initial phase of septic shock. 2. In
      pithed and vagotomized rats treated with pancuronium, electrical stimulation (ES)
      (1 Hz, 1 ms, 50 V for 10 s) of the preganglionic sympathetic nerve fibers or
      intravenous bolus injection of noradrenaline (NA) (1-3 nmol x kg(-1)) increased
      the diastolic blood pressure (DBP) by about 30 mmHg. Administration of LPS (0.4
      and 4 mg x kg(-1)) under continuous infusion of vasopressin inhibited the
      neurogenic vasopressor response by 25 and 50%, respectively. LPS did not affect
      the increase in DBP induced by exogenous NA. 3. The LPS-induced inhibition of the
      neurogenic vasopressor response was counteracted by the cannabinoid CB(1)
      receptor antagonist SR 141716A (0.1 micromol x kg(-1)), but not by the CB(2)
      receptor antagonist SR 144528 (3 micromol x kg(-1)), the vanilloid VR1 receptor
      antagonist capsazepine (1 micromol x kg(-1)) or the histamine H(3) receptor
      antagonist clobenpropit (0.1 micromol x kg(-1)). The four antagonists by
      themselves did not affect the increase in DBP induced by ES or by injection of NA
      in rats not exposed to LPS. 4. We conclude that in the initial phase of septic
      shock, the activation of presynaptic CB(1) receptors by endogenously formed
      cannabinoids contributes to the inhibition of the neurogenic vasopressor
      response.

PMID- 15159285
TI  - Steroid prophylaxis for prevention of nerve function impairment in leprosy:
      randomised placebo controlled trial (TRIPOD 1).
AB  - OBJECTIVE: To determine whether addition of low dose prednisolone to multidrug
      treatment can prevent reaction and nerve function impairment in leprosy. DESIGN:
      Multicentre, double blind, randomised, placebo controlled, parallel group trial.
      SETTING: Six centres in Bangladesh and Nepal. PARTICIPANTS: 636 people with newly
      diagnosed multibacillary leprosy. INTERVENTION: Prednisolone 20 mg/day for three
      months, with tapering dose in month 4, plus multidrug treatment, compared with
      multidrug treatment alone. MAIN OUTCOME MEASURES: Signs of reaction, impairment
      of sensory and motor nerve function, and nerve tenderness needing full dose
      prednisolone at four months and one year. RESULTS: Prednisolone had a significant
      effect in the prevention of reaction and nerve function impairment at four months
      (relative risk 3.9, 95% confidence interval 2.1 to 7.3), but this was not
      maintained at one year (relative risk 1.3, 0.9 to 1.8). Fewer events occurred in
      the prednisolone group at all time points up to 12 months, but the difference at
      12 months was small. Subgroup analysis showed a difference in response between
      people with and without impairment of nerve function at diagnosis. CONCLUSIONS:
      The use of low dose prophylactic prednisolone during the first four months of
      multidrug treatment for leprosy reduces the incidence of new reactions and nerve
      function impairment in the short term, but the effect is not sustained at one
      year. The presence of nerve function impairment at diagnosis may influence the
      response to low dose prednisolone.

PMID- 15159286
TI  - Incidence of high-strain patterns in human coronary arteries: assessment with
      three-dimensional intravascular palpography and correlation with clinical
      presentation.
AB  - BACKGROUND: Rupture of thin-cap fibroatheromatous plaques is a major cause of
      acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D
      intravascular palpography with high sensitivity and specificity. We used this
      technique in patients undergoing percutaneous intervention to assess the
      incidence of mechanically deformable regions. We further explored the relation of
      such regions to clinical presentation and to C-reactive protein levels. METHOD
      AND RESULTS: Three-dimensional palpograms were derived from continuous
      intravascular ultrasound pullbacks. Patients (n=55) were classified by clinical
      presentation as having stable angina, unstable angina, or AMI. In every patient,
      1 coronary artery was scanned (culprit vessel in stable and unstable angina,
      nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable
      angina patients had significantly fewer deformable plaques per vessel (0.6+/-0.6)
      than did unstable angina patients (P=0.0019) (1.6+/-0.7) or AMI patients
      (P<0.0001) (2.0+/-0.7). Levels of C-reactive protein were positively correlated
      with the number of mechanically deformable plaques (R2=0.65, P<0.0001).
      CONCLUSIONS: Three-dimensional intravascular palpography detects strain patterns
      in human coronary arteries that represent the level of deformation in plaques.
      The number of highly deformable plaques is correlated with both clinical
      presentation and levels of C-reactive protein. Further studies will assess the
      potential role of the technique to identify patients at risk of future clinical
      events

PMID- 15159287
TI  - Serum total homocysteine concentrations and risk of stroke and its subtypes in
      Japanese.
AB  - BACKGROUND: To date, no prospective studies have examined the association between
      serum homocysteine levels and the risk of stroke and stroke subtypes in Asian
      populations. METHODS AND RESULTS: A prospective, nested, case-control study of
      Japanese subjects 40 to 85 years of age was conducted by using frozen serum
      samples from 11 846 participants in cardiovascular risk surveys collected from
      1984 to 1995 for one community and 1989 to 1995 for the other two communities. By
      the end of 2000, we identified 150 incident strokes, the subtypes of which were
      confirmed by imaging studies. Three control subjects per case were selected by
      matching for sex, age, community, year of serum storage, and fasting status.
      Serum total homocysteine levels were measured by high-performance liquid
      chromatography. Compared with control subjects, total (n=150), hemorrhagic
      (n=52), and ischemic (n=98) strokes had higher geometric mean values of total
      homocysteine and higher proportions of homocysteine > or =11.0 micromol/L. The
      multivariate odds ratios (95% CI) for highest (> or =11.0 micromol/L) versus
      lowest quartiles (<7.0 micromol/L) of homocysteine after adjustment for body mass
      index, smoking, alcohol intake, hypertension, serum total cholesterol, and other
      cardiovascular risk factors were 2.99 (1.51 to 5.93) for total stroke, 3.89 (1.60
      to 9.46) for ischemic stroke, 3.36 (1.27 to 8.90) for lacunar infarction, and
      1.63 (0.44 to 6.00) for hemorrhagic stroke. The respective multivariate odds
      ratios associated with a 5-micromol/L increase in homocysteine were 1.40 (1.09 to
      1.80), 1.52 (1.07 to 2.14), 1.48 (1.01 to 2.18), and 1.10 (0.76 to 1.59). The
      excess risk of total and ischemic strokes did not vary significantly according to
      sex, age, smoking status, or hypertensive status. CONCLUSIONS: High total
      homocysteine concentrations were associated with the increased risk of total
      stroke, more specifically ischemic stroke and lacunar infarction, among Japanese
      men and women.

PMID- 15159288
TI  - Aldosterone potentiates angiotensin II-induced signaling in vascular smooth
      muscle cells.
AB  - BACKGROUND: In a double-transgenic human renin and human angiotensinogen rat
      model, we found that mineralocorticoid receptor (MR) blockade ameliorated
      angiotensin II (Ang II)-induced renal and cardiac damage. How Ang II and
      aldosterone (Ald) might interact is ill defined. METHODS AND RESULTS: We
      investigated the effects of Ang II (10(-7) mol/L) and Ald (10(-7) mol/L) on
      extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)
      signaling in vascular smooth muscle cells (VSMCs) with Western blotting and
      confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 minutes.
      Ald achieved the same at 10 minutes. Ang II+Ald had a potentiating effect by 2
      minutes. Two oxygen radical scavengers and the epidermal growth factor receptor
      (EGFR) antagonist AG1478 reduced Ang II-, Ald-, and combination-induced ERK1/2
      phosphorylation. Preincubating the cells with the MR blocker spironolactone (10(
      6) mol/L) abolished Ang II-induced ROS generation, EGFR transactivation, and
      ERK1/2 phosphorylation. CONCLUSIONS: Ald potentiates Ang II-induced ERK-1/2 and
      JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early
      signaling induced by Ang II and Ald in VSMCs. These in vitro data may help
      explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.

PMID- 15159289
TI  - Determinants of arterial nitrate-mediated dilatation in children: role of
      oxidized low-density lipoprotein, endothelial function, and carotid intima-media
      thickness.
AB  - BACKGROUND: Impaired arterial dilatation response to nitroglycerin has been
      observed in adults with risk factors for atherosclerosis and in patients with
      established atherosclerotic disease. This defect parallels changes in vascular
      endothelial function and may be attributed to increased oxidative stress. Because
      atherosclerosis begins in childhood, we examined the correlates of nitrate
      mediated dilatation (NMD) in children, including brachial artery endothelial
      function, oxidized LDL, and carotid artery intima-media thickness (IMT). METHODS
      AND RESULTS: Brachial artery flow-mediated endothelium-dependent dilatation (FMD)
      and nitrate-mediated smooth muscle function, IMT of the carotid bulb, and
      brachial artery and oxidized LDL were measured in 142 children (mean age, 11
      years; range, 8 to 17 years), including 87 healthy children, 41 diabetic
      children, and 14 children with familial hypercholesterolemia. NMD correlated
      directly with FMD (r=0.46, P<0.001) and inversely with brachial artery baseline
      diameter (r=-0.36, P<0.001), age (r=-0.25, P=0.003), body mass index (r=-0.31,
      P<0.001), diabetes (r=-0.22, P=0.008), oxidized LDL (r=-0.18, P=0.045), and IMT
      (r=-0.33, P<0.001). In a multivariate regression model, the significant
      correlates for NMD were FMD response (beta=0.003, P<0.001), brachial artery
      diameter (beta=-0.03, P=0.01), oxidized LDL (beta=-0.07, P=0.02), and IMT (beta=
      0.15, P=0.03). CONCLUSIONS: Reduced endothelial function, increased oxidative
      stress, and preclinical carotid atherosclerosis are independent determinants of
      impaired NMD in children. These data thus suggest that primary nitrate tolerance
      occurs in children at risk for atherosclerosis.

PMID- 15159290
TI  - Long-term outcome of renal transplant recipients in the United States after
      coronary revascularization procedures.
AB  - BACKGROUND: Retrospective studies in dialysis patients have reported increased
      survival after coronary artery bypass (CAB) compared with coronary artery
      stenting and PTCA. The purpose of this study was to compare the long-term outcome
      of renal transplant recipients after stent, PTCA, or CAB with or without internal
      mammary grafting (CAB [IMG+] or CAB [IMG-]). METHODS AND RESULTS: Renal
      transplant recipients hospitalized from 1995 to 1999 for first coronary
      revascularization procedure were retrospectively identified from the United
      States Renal Data System database. Event-free survival for the end points of all
      cause death, cardiac death, acute myocardial infarction (AMI), and the combined
      end point of cardiac death or AMI was estimated by the life-table method. The
      impact of independent predictors on survival was examined in a comorbidity
      adjusted Cox model. In-hospital mortality rate was 2.3% for 909 stent patients,
      4.3% for 652 PTCA patients, 9.4% for 288 CAB (IMG-) patients, and 5.0% for 812
      CAB (IMG+) patients. Two-year all-cause survival (+/-SE) was: stent, 82.5+/-2.8%;
      PTCA, 81.6+/-3.1%; CAB (IMG-), 74.4+/-5.4%; and CAB (IMG+), 82.7+/-2.8%. The
      relative risks of all-cause and cardiac death were not significantly different
      among revascularization groups. The relative risk of cardiac death or AMI (versus
      PTCA) was 0.90 (95% CI, 0.69 to 1.17) for stent, 0.80 (95% CI, 0.55 to 1.17) for
      CAB (IMG-), and 0.57 (95% CI, 0.42 to 0.76) for CAB (IMG+). CONCLUSIONS: Renal
      transplant recipients in the United States have comparable long-term survival
      after percutaneous and surgical coronary revascularization procedures. The most
      favorable long-term outcome occurs after surgical coronary revascularization.

PMID- 15159291
TI  - CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid
      arthritis patients.
AB  - BACKGROUND: Peripheral blood expansion of an unusual CD4+ T-cell subset lacking
      surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients
      to develop more aggressive disease. However, the potential association between
      CD4+CD28null T cells and early atherosclerotic changes in RA has never been
      investigated. METHODS AND RESULTS: The number of circulating CD4+CD28null cells
      was evaluated in 87 RA and 33 control subjects who also underwent evaluation of
      carotid artery intima-media thickness (IMT) and endothelial function via flow
      mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with
      control subjects. The frequency of CD4+CD28null cells was significantly higher in
      patients than in control subjects. Twenty patients with persistent expansion of
      circulating CD4+CD28null cells had more marked increase of carotid artery IMT and
      stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-alpha
      led to a partial reappearance of the CD28 molecule on the CD4+ cell surface.
      CONCLUSIONS: Circulating CD4+CD28(null) lymphocytes are increased in RA. Patients
      with persistent CD4+CD28null cell expansion show preclinical atherosclerotic
      changes, including arterial endothelial dysfunction and carotid artery wall
      thickening, more significantly than patients without expansion. These findings
      suggest a contribution of this cell subset in atheroma development in RA.
      Moreover, the demonstration that tumor necrosis factor-alpha blockade is able to
      reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of
      interest for possible innovative therapeutic strategies in cardiovascular
      diseases.

PMID- 15159292
TI  - Surgical ventricular restoration improves mechanical intraventricular
      dyssynchrony in ischemic cardiomyopathy.
AB  - BACKGROUND: In ischemic cardiomyopathy, dyssynchrony of left ventricular (LV)
      mechanical contraction produces adverse hemodynamic consequences. This study
      tests the capacity of geometric rebuilding by surgical ventricular restoration
      (SVR) to restore a more synchronous contractile pattern after a mechanical,
      rather than electrical, intervention. METHODS AND RESULTS: A prospective study of
      the global and regional components of dyssynchrony was conducted in 30 patients
      (58+/-8 years of age) undergoing SVR at the Cardiothoracic Center of Monaco. The
      protocol used simultaneous measurements of ventricular volumes and pressure to
      construct pressure/volume (P/V) and pressure/length (P/L) loops. Angiograms were
      done before and after SVR to study a 600-ms cycle during atrial pacing at 100
      bpm. Mean QRS duration was similar, at 100+/-17 ms preoperatively and 114+/-28 ms
      postoperatively (NS). Preoperative LV contraction was highly asynchronous,
      because P/V loops showed abnormal isometric phases with a right shifting.
      Endocardial time motion was either early or delayed at the end-systolic phase so
      that P/L loops were markedly abnormal in size, shape, and orientation.
      Postoperatively, SVR resulted in leftward shifting of P/V loops and increased
      area; endocardial time motion and P/L loops almost normalized to allow a better
      contribution of single regions to global ejection. The hemodynamic consequences
      of SVR were improved ejection fraction (30+/-13% to 45+/-12%; P=0.001); reduced
      end-diastolic and end-systolic volume index (202+/-76 to 122+/-48 and 144+/-69 to
      69+/-40 mL/m(2); P=0.001); more rapid peak filling rate (1.75+/-0.7 to 2.32+/-0.7
      EDV/s; P=0.0001); peak ejection rate (1.7+/-0.7 to 2.6+/-0.9 Sv/s; P=0.0002), and
      mechanical efficiency (0.56+/-0.15 to 0.65+/-0.18; P=0.04). CONCLUSIONS: SVR
      produces a mechanical intraventricular resynchronization that improves LV
      performance.

PMID- 15159293
TI  - Prognostic assessment of patients with acute myocardial infarction treated with
      primary angioplasty: implications for early discharge.
AB  - BACKGROUND: The aim of this study was to create a practical score for risk
      stratification in patients with ST-segment elevation myocardial infarction
      (STEMI) treated with primary angioplasty and to assess the feasibility of early
      discharge in low-risk patients. METHODS AND RESULTS: A prognostic score was built
      according to 30-day mortality rates in 1791 patients undergoing primary
      angioplasty for STEMI. For the identified low-risk patients without any
      contraindication to early discharge, we estimated and compared the costs of
      conventional care (prolonged 24-hour hospitalization) with the costs of shifting
      the care from inpatient to outpatient setting (early discharge) between 48 and 72
      hours. Independent predictors of 30-day mortality included in the score were age,
      anterior infarction, Killip class, ischemic time, postprocedural Thrombolysis In
      Myocardial Infarction (TIMI) flow, and multivessel disease. This score was able
      to identify a large cohort (73.4%) of low-risk (score < or =3) patients, with a
      good discriminatory capacity (c statistic=0.907). The mortality rate was 0.1% at
      2 days and 0.2% between 2 and 10 days in patients with a score < or =3. The
      incremental cost-effectiveness ratio for late discharge in low-risk patients was
      estimated at 1949.33. Therefore, this policy would save 1 life per 1097 low-risk
      patients, at additional costs of 194 933.33, in comparison with an early
      discharge policy. CONCLUSIONS: This score is a practical and useful index for
      risk stratification after primary angioplasty for STEMI, with a significant
      impact on clinical decision-making and the related costs. It reliably identifies
      a large group of patients at very low risk, who may safely be discharged early
      after primary angioplasty.

PMID- 15159294
TI  - Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation
      of atrial fibrillation.
AB  - BACKGROUND: Radiofrequency ablation for atrial fibrillation is becoming widely
      practiced. METHODS AND RESULTS: Two patients undergoing circumferential pulmonary
      vein ablation for atrial fibrillation in different centers developed symptoms
      compatible with endocarditis 3 to 5 days after the procedure. Their clinical
      condition deteriorated rapidly, and both suffered multiple gaseous and/or septic
      embolic events causing cerebral and myocardial damage. One patient survived after
      emergency cardiac and esophageal surgery; the other died of extensive systemic
      embolization. An atrio-esophageal fistula was identified in both patients.
      CONCLUSIONS: Atrio-esophageal fistulas can occur after catheter ablation in the
      posterior wall of the left atrium. This diagnosis should be excluded in any
      patient with symptoms or signs of endocarditis after left atrial ablation, and
      expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower
      power and temperature settings for applications of radiofrequency energy along
      the posterior left atrial wall may prevent further cases of fistula formation.

PMID- 15159295
TI  - Intra-arrest cooling improves outcomes in a murine cardiac arrest model.
AB  - BACKGROUND: Recent clinical studies have demonstrated that hypothermia to 32
      degrees to 34 degrees C provides significant clinical benefit when induced after
      resuscitation from cardiac arrest. However, cooling during the postresuscitation
      period was slow, requiring 4 to 8 hours to achieve target temperatures after
      return of spontaneous circulation (ROSC). Whether more rapid cooling would
      further improve survival remains unclear. We sought to determine whether cooling
      during cardiac arrest before ROSC (ie, "intra-arrest" hypothermia) has survival
      benefit over more delayed post-ROSC cooling, using a murine cardiac arrest model.
      METHODS AND RESULTS: A model of potassium-induced cardiac arrest was established
      in C57BL/6 mice. After 8 minutes of untreated cardiac arrest, resuscitation was
      attempted with chest compression, ventilation, and intravenous fluid. Mice were
      randomized to 3 treatment groups (n=10 each): an intra-arrest hypothermia group,
      in which mice were cooled to 30 degrees C just before attempted resuscitation,
      and then rewarmed after 1 hour; a post-ROSC hypothermia group, in which mice were
      kept at 37 degrees C for 20 minutes after successful ROSC and then were cooled to
      30 degrees C for 1 hour; and a normothermic control group, in which mice were
      kept at 37 degrees C. The intra-arrest hypothermia group demonstrated better 72
      hour survival than delayed hypothermia and normothermia groups (6/10 versus 1/10
      and 1/10 survivors, respectively, P<0.05), with similar differences seen at 6
      hour survival and on neurological scoring. CONCLUSIONS: Timing of hypothermia is
      a crucial determinant of survival in the murine arrest model. Early intra-arrest
      cooling appears to be significantly better than delayed post-ROSC cooling or
      normothermic resuscitation.

PMID- 15159296
TI  - Race-specific differences in endothelial function: predisposition of African
      Americans to vascular diseases.
AB  - BACKGROUND: The prevalence of the endothelium-impaired function disorders, such
      as hypertension and diabetes mellitus, and the severity of their complications
      are considerably greater in blacks than whites. Evidence has accumulated that
      superoxide (O2-) production and its interaction with nitric oxide (NO), yielding
      the strong oxidant peroxynitrite (ONOO-), play central roles in vascular
      pathophysiology. We hypothesized that the differences in endothelial NO/O2-/ONOO-
      metabolism may highlight the potential predisposition to endothelial dysfunction
      and cardiovascular complications prevalent in blacks. METHODS AND RESULTS: Highly
      sensitive tandem electrochemical NO/O2-/ONOO- nanosensors were positioned in
      single human umbilical vein endothelial cells (HUVECs) isolated from blacks and
      whites, and the kinetics of NO/O2-/ONOO- release were recorded in vitro. HUVECs
      were also analyzed by Western immunoblotting and enzyme activity assays for
      NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with whites, HUVECs
      from blacks elicited reduced release of bioactive NO with an accompanying
      increase in the release of both O2- and ONOO-. The greater potency of NO
      production because of eNOS upregulation in HUVECs from blacks is associated with
      a decrease in the NO bioavailability. This is due to increased NO degradation by
      excess O2- produced primarily by 2 enzymatic sources: NAD(P)H-oxidase and
      uncoupled eNOS. CONCLUSIONS: Compared with whites, the steady-state NO/O2-/ONOO-
      balance in endothelial cells from blacks is kept closer to the redox states
      characteristic for the endothelium-impaired function disorders. This may explain
      the differences in racial predisposition to the endothelium dysfunction during
      ongoing vascular disturbances with the hallmark of enhanced NO inactivation
      within the endothelium by oxidative stress.

PMID- 15159297
TI  - SNPs, haplotypes, and cancer: applications in molecular epidemiology.

PMID- 15159298
TI  - Epstein-Barr virus and breast cancer: state of the evidence for viral
      carcinogenesis.
AB  - As the etiology and progression of breast cancer remain incompletely understood,
      novel routes of disease pathogenesis are important to consider. Viral pathogens
      have not been much explored, but recent interest has focused on Epstein-Barr
      virus (EBV). Studies of an association of this ubiquitous herpesvirus with breast
      cancer have had notably inconsistent results, marked by varying EBV presence
      (from 0% to 50% of tumors) and the absence of certain viral characteristics found
      in other EBV-related malignancies. The research has been plagued by the technical
      challenges of localizing EBV to tumor cells and by a tendency to overlook
      epidemiological cofactors, shown in all other EBV-related cancers to impact the
      EBV association. Breast cancer studies to date have used several viral detection
      methods of varying or uncertain sensitivity and specificity; most have involved
      small and/or poorly characterized case series and paid insufficient attention to
      epidemiological cofactors relevant to breast cancer and to EBV-related
      malignancies. Given these limitations and the established complexity of the
      connection of EBV with other cancers, a definitive judgment regarding the
      presence of this virus in breast cancer cannot yet be rendered. Recent advances
      in laboratory methodologies should help overcome the challenges of EBV detection
      in breast cancers. Further research is warranted, given the potential for an EBV
      association to inform not only breast cancer etiology but also early detection,
      treatment, and prevention.

PMID- 15159299
TI  - Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary
      phytoestrogen intake and their relation to breast cancer risk in European
      prospective investigation of cancer and nutrition-norfolk.
AB  - Subjects of this study consisted of 333 women (aged 45-75 years) drawn from a
      large United Kingdom prospective study of diet and cancer, the European
      Prospective Investigation of Cancer and Nutrition-Norfolk study. Using newly
      developed gas chromatography/mass spectrometry and liquid chromatography/mass
      spectrometry methods incorporating triply (13)C-labeled standards, seven
      phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol,
      enterodiol, and enterolactone) were measured in 114 spot urines and 97 available
      serum samples from women who later developed breast cancer. Results were compared
      with those from 219 urines and 187 serum samples from healthy controls matched by
      age and date of recruitment. Dietary levels were low, but even so, mean serum
      levels of phytoestrogens were up to 600 times greater than postmenopausal
      estradiol levels. Phytoestrogen concentrations in spot urine (adjusted for
      urinary creatinine) correlated strongly with that in serum, with Pearson
      correlation coefficients > 0.8. There were significant relationships (P < 0.02)
      between both urinary and serum concentrations of isoflavones across increasing
      tertiles of dietary intakes. Urinary enterodiol and enterolactone and serum
      enterolactone were significantly correlated with dietary fiber intake (r = 0.13
      0.29). Exposure to all isoflavones was associated with increased breast cancer
      risk, significantly so for equol and daidzein. For a doubling of levels, odds
      ratios increased by 20-45% [log(2) odds ratio = 1.34 (1.06-1.70; P = 0.013) for
      urine equol, 1.46 (1.05-2.02; P = 0.024) for serum equol, and 1.22 (1.01-1.48; P
      = 0.044) for serum daidzein]. These estimates of risk are similar to those
      established for estrogens and androgens in postmenopausal breast cancer but need
      confirmation in larger studies.

PMID- 15159300
TI  - Population-based case-control study of CYP11A gene polymorphism and breast cancer
      risk.
AB  - The CYP11A gene encodes the cholesterol side-chain cleavage enzyme (P450scc) that
      catalyzes the first and rate-limiting step for the biosynthesis of sex hormones.
      A pentanucleotide repeat [(TAAAA)n] polymorphism in the 5' of the CYP11A gene has
      been reported to be related to the risk of polycystic ovary syndrome, an
      inherited endocrine disorder characterized by hyperandrogenemia. We investigated
      the association of this polymorphism with breast cancer risk in a population
      based case-control study conducted among Chinese women in Shanghai. Genotype
      assays were completed for 1015 incident breast cancer cases and 1082 community
      controls. Three common alleles with 4, 6, or 8 TAAAA repeats were identified in
      the study population. The frequency of the 8 repeat allele was more common in
      cases (12.6%) than controls (8.5%) (odds ratio = 1.6, 95% confidence interval =
      1.3-1.9; P < 0.0001). Compared to subjects who did not carry this allele,
      adjusted odds ratios were 1.5 (95% confidence interval = 1.2-1.9) and 2.9 (1.3
      6.7) (P for trend, <0.001), respectively, for those who carried one and two
      copies of this allele. This positive association was observed in both pre- and
      postmenopausal women and all strata defined by major breast cancer risk factors,
      including years of menstruation, body mass index, and waist-to-hip ratio. The
      results from this study indicate that the TAAAA repeat polymorphism near the
      promoter region of the CYP11A gene may be an important susceptibility factor for
      breast cancer risk.

PMID- 15159301
TI  - A prospective study of breast cancer risk using routine mammographic breast
      density measurements.
AB  - Mammographic breast density is a major risk factor for breast cancer but
      estimates of the relative risk associated with differing density patterns have
      varied widely. It is also unclear how menopausal status influences this
      association and to what extent the effects of density are due to its correlation
      with other risk factors. Most recent investigations of breast density have been
      case-control studies, which provide indirect estimates of relative risk. We have
      prospectively followed 61,844 women for an average of 3.1 years to directly
      estimate risk among women in the four mammographic breast density categories
      defined by the American College of Radiology's Breast Imaging Reporting and Data
      System (BI-RADS). The study was population-based and used density assessments
      routinely made by community radiologists. Cox regression was used to obtain age
      adjusted relative risk estimates and to control for other risk factors. Risk
      increased with density and the risk associated with extremely dense breasts,
      relative to entirely fatty breasts, was 4.6 (95% confidence interval, 1.7-12.6)
      for premenopausal women and 3.9 (95% confidence interval, 2.6-5.8) for
      postmenopausal women. Estimates for pre- and postmenopausal women did not differ
      significantly. Although breast density was significantly related to body mass
      index, age at first childbirth, and postmenopausal hormone use (P < 0.001),
      adjustment for these variables only slightly altered the relative risk estimates.
      Our results correspond well to those from case-control studies using more
      quantitative measures of mammographic breast density and suggest that routine
      Breast Imaging Reporting and Data System density measurements may be useful in
      models for assessing breast cancer risk in individual women.

PMID- 15159302
TI  - What factors are associated with diagnostic follow-up after abnormal mammograms?
      Findings from a U.S. National Survey.
AB  - The purpose of this study was to identify factors associated with diagnostic
      follow-up after an abnormal mammogram in a national sample of women in the U.S.
      The sample was selected from the year 2000 National Health Interview Survey and
      included 1901 women aged 30 and above who reported ever having an abnormal
      mammogram. The outcome measure was receipt of at least some diagnostic follow-up
      after an abnormal mammogram. Bivariate and multivariate logistic regression
      analyses were used to explore the associations between sociodemographic
      characteristics, general health and health behaviors, cancer risk and risk
      perceptions, and health care utilization characteristics and follow-up.
      Approximately 9% of women who reported ever having abnormal mammograms reported
      not completing any additional diagnostic follow-up. Controlling for all other
      factors, women with less than a high school education were less likely to report
      follow-up after an abnormal mammogram than were women who had at least completed
      college (odds ratio = 0.56; 95% confidence interval: 0.32, 0.98). Younger women
      and women in poorer health were also less likely to report follow-up. Women who
      perceived a high versus low level of cancer in their family were more likely to
      report follow-up (odds ratio = 1.65; 95% confidence interval: 1.04, 2.62),
      controlling for all other factors. In a national sample of women with abnormal
      mammograms, a substantial number did not complete any diagnostic follow-up,
      potentially reducing the effectiveness of mammography screening programs in the
      U.S. Additional research on subsequent screening behaviors for women with
      incomplete follow-up and in-depth exploration of the roles of patient-provider
      interactions and health care system factors related to the index abnormal
      mammogram is warranted.

PMID- 15159303
TI  - Fertility intentions following testing for a BRCA1 gene mutation.
AB  - OBJECTIVE: To test whether fertility intentions differed among persons who tested
      positive, tested negative, or did not know their genetic status for a mutation of
      the BRCA1 gene. METHOD: Participants were members of a large Utah-based kindred
      with an identified mutation at the BRCA1 locus. Participants received genetic
      counseling prior to testing and were interviewed at baseline before testing and
      at three points after receiving test results from a genetic counselor. The sample
      included men and women who completed all interviews, were between ages 18 and 45,
      and were fertile, resulting in a sample of 101 respondents. The primary dependent
      variable measured whether a subject indicated that they were moderately or very
      sure at all three post-testing interviews that they intended to have additional
      children. Effects of BRCA1 mutation status on fertility intentions were estimated
      using multivariate logistic regressions where we controlled for gender, age,
      marital status, and baseline fertility intentions. RESULTS: Female carriers were
      less likely to want additional children in relation to female noncarriers (odds
      ratio 0.12, 95% confidence interval 0.01-1.23; P = 0.074). No differences were
      found among men. There was a significant difference in the effect of mutation
      status on fertility intentions between males and females (Gender x Carrier status
      interaction; P = 0.009). Persons who did not know their mutation status were less
      likely to want more children than noncarriers (odds ratio 0.09, 95% confidence
      interval 0.01-0.75; P = 0.027). CONCLUSION: Predictive genetic testing for late
      onset cancer susceptibility affects family planning decision-making. Persons
      contemplating predictive testing should be informed about possible effects such
      testing may have on their plans for future fertility.

PMID- 15159304
TI  - Relation between intervention exposures, changes in attitudes, and mammography
      use in the North Carolina Breast Cancer Screening Program.
AB  - OBJECTIVE: Many past interventions have been based on the assumption that
      improving attitudes about mammography can increase mammography use. We studied
      changes in breast cancer and mammography attitudes over time in mediating the
      effect of intervention exposures on mammography use in the North Carolina Breast
      Cancer Screening Program. Data came from interviews with a cohort of 331 black
      women who said they had heard of mammography at baseline interview. METHODS: We
      created scores and score changes for mammography (7 items) and breast cancer (11
      items) attitudes at baseline (1993-1994) and follow-up interviews (1996-1997). We
      modeled intervention exposures, attitude changes, and mammography use in linear
      risk and logistic regression. Intervention exposures were defined for mammography
      discussion with a project lay health advisor ("LHA advice"), mammography
      discussion with anyone besides a doctor or nurse, and project awareness. RESULTS:
      Positive change in mammography attitudes was associated with intervention
      exposures and mammography use and appeared to account for a large percentage (34
      98%) of the effect of mammography discussion variables on increased mammography
      use. Greatest effect of attitude improvement was found for women without a recent
      mammogram at baseline and with the least positive baseline attitude scores.
      CONCLUSION: Using cohort data enabled us to examine the role of attitude change
      over time on mammography use. Breast cancer screening programs should target
      women with the most negative mammography attitudes and the least mammography use
      to start with and concentrate their messages on improving attitudes specific to
      mammography rather than improving attitudes about breast cancer risk.

PMID- 15159305
TI  - Increased plasma levels of insulin-like growth factor 2 and insulin-like growth
      factor binding protein 3 are associated with endometrial cancer risk.
AB  - Circulating insulin-like growth factors (IGFs) and their binding proteins have
      been associated with increased risk of breast, prostate, colon, and lung cancer.
      To examine the association of IGFs and endometrial cancer risk, we measured the
      plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80
      women with endometrial cancer and 80 age-matched control subjects with no history
      of cancer. Mean plasma levels of IGF-2 were significantly higher in women with
      cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.001). In contrast,
      significantly lower mean plasma levels of IGF-1 (155 mg/ml versus 185 ng/ml, P <
      0.01) and IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P < 0.001) were observed among
      cases compared to the control group. Women in the highest quartile of IGF-2 were
      found to have 9.67 (95% confidence interval 3.29-28.43) times the risk of
      endometrial cancer than women in the lowest quartiles. Women in the highest
      quartile of IGFBP-3 were associated with a significantly decreased risk for
      developing endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09
      0.60). These data suggest that increased plasma levels of IGF-2 and decreased
      levels of IGFBP-3 are associated with an increased risk of endometrial cancer.
      Further validation of these results is needed to determine the potential
      usefulness of risk assessment.

PMID- 15159306
TI  - Factors predicting prostate specific antigen testing among first-degree relatives
      of prostate cancer patients.
AB  - First-degree relatives (FDRs) of prostate cancer patients are known to be at
      increased risk for the disease, yet relatively little is known about their
      screening behaviors. The current lack of consensus about the value of prostate
      cancer screening underscores the importance of examining why some men at
      increased risk participate in screening and others do not. In this study,
      variables from Protection Motivation Theory were used to identify predictors of
      prostate specific antigen (PSA) testing in this at-risk population. Toward this
      end, scales assessing perceived vulnerability, perceived severity, response
      efficacy, and self-efficacy for prostate cancer screening were administered to 82
      unaffected male FDRs aged 40 and older. When recontacted approximately 14 months
      later, 50% of FDRs were found to have undergone PSA testing in the interim. Older
      age, prior prostate cancer screening, and a greater sense of personal efficacy
      about being able to undergo prostate cancer screening were found to be
      significant (P < 0.05) predictors of subsequently undergoing PSA testing. These
      findings provide partial support for the predictive validity of Protection
      Motivation Theory variables and suggest the importance of considering efficacy
      beliefs in attempting to understand decision-making about PSA testing in at-risk
      individuals.

PMID- 15159307
TI  - A gain of function TGFB1 polymorphism may be associated with late stage prostate
      cancer.
AB  - Transforming growth factor beta (TGFbeta) is known to exert both positive and
      negative effects on different stages of tumor formation. Of the TGFbetaisoforms,
      TGFbeta1 is highly expressed in prostate cancer and leads to tumor promotion and
      metastasis. Increased expression of TGFbeta1 is associated with more aggressive
      tumors and poor prognosis. Several polymorphisms in TGFB1 have been identified,
      and two variants in strong linkage disequilibrium, C-509T and T+29C, show
      increased serum levels. Because of the potential role of TGFB1 variants in
      prostate cancer and progression, we hypothesized that these two TGFB1 variants
      would be associated with prostate cancer risk, particularly later, more
      aggressive stage tumors. To test this, we conducted a nested case-control study
      of 492 men diagnosed with prostate cancer from the Physicians Health Study and
      492 age-matched controls. In this study, cases who were homozygous for the T
      allele at position -509 had a 2.4-fold increased risk of more advanced stage of
      prostate cancer [95% confidence interval (95% CI) 1.03-5.43; P = 0.04]. The T
      allele frequencies in cases and controls were 32.7% and 31.4%, respectively. The
      same polymorphism showed a 1.23 nonsignificant odds ratio (OR) for overall
      prostate cancer risk (95% CI 0.80-1.87). Cases who were homozygous for the C
      allele at position +29 did not show any significant increase in risk for either
      total prostate cancer (OR 1.19, 95% CI 0.82-1.74) or advanced stage prostate
      cancer (OR 1.33, 95% CI 0.66-2.68). The C allele frequency in cases and controls
      were 39.9% and 38.5%, respectively. Our data suggest that the TGFB1 C-509T
      variant that affects expression of TGFbeta1 may play a role in advanced stage
      prostate cancer.

PMID- 15159308
TI  - Physical activity and risk of ovarian cancer: a prospective cohort study in the
      United States.
AB  - Increased physical activity may lower the risk of ovarian cancer by reducing the
      frequency of ovulation, decreasing body fat, or diminishing chronic inflammation.
      Previous epidemiological studies examining the association between physical
      activity and risk of ovarian cancer have been inconsistent. We investigated the
      association of physical activity with ovarian cancer in a prospective cohort of
      27,365 individuals from the Breast Cancer Detection Demonstration Project. During
      227,045 person-years of follow-up, 121 cases of ovarian cancer were ascertained.
      Usual physical activity during the past year was assessed by a self-administered
      questionnaire. After adjusting for potential risk factors for ovarian cancer, the
      relative risks (95% confidence intervals) across increasing quintiles of total
      physical activity were 1.0, 0.73 (0.43-1.25), 0.84 (0.50-1.40), 0.56 (0.31-1.00),
      and 0.70 (0.41-1.21), respectively (P for trend = 0.13). In this prospective
      cohort study among U.S. women, we found no overall significant association
      between physical activity and risk of ovarian cancer, although the results are
      suggestive of an inverse association.

PMID- 15159309
TI  - Selenium and lung cancer: a quantitative analysis of heterogeneity in the current
      epidemiological literature.
AB  - While numerous laboratory investigations have shown that selenium may have
      anticarcinogenic activity, the epidemiological data have been inconsistent. In
      this report, meta-analysis was used to quantitatively summarize the existing
      epidemiological evidence on selenium and lung cancer and identify sources of
      heterogeneity among studies. When all studies were combined, the summary relative
      risk (RR) for subjects with higher selenium exposures was 0.74 [95% confidence
      interval (CI) 0.57-0.97]. In subgroup analyses based on the average selenium
      level in the study population, the summary RR for areas where selenium levels
      were low was 0.72 (95% CI 0.45-1.16), while the RR for areas where selenium
      levels were higher was 0.86 (95% CI 0.61-1.22). In both studies in high selenium
      areas where RRs were markedly below 1.0, protective effects were only found when
      subjects in the lowest category of selenium exposure were used as referents. No
      clear protective effects were seen when highly exposed subjects were compared
      with those in the middle exposure categories. The summary RR was lower in studies
      assessing selenium exposure using toenails (RR 0.46, 95% CI 0.24-0.87) than in
      studies using serum selenium (RR 0.80, 95% CI 0.58-1.10) or studies assessing
      dietary intake (RR 1.00, 95% CI 0.77-1.30). Overall, these results suggest that
      selenium may have some protective effect against lung cancer in populations where
      average selenium levels are low. The evidence for these findings is greater in
      studies of toenail selenium than in studies involving other measures of exposure.

PMID- 15159310
TI  - Body mass index, leptin and leptin receptor polymorphisms, and non-hodgkin
      lymphoma.
AB  - In a population-based case-control study, obesity was associated with elevated
      odds ratios (ORs) for non-Hodgkin lymphoma (NHL), and the two major subtypes,
      diffuse large cell (DLCL) and follicular lymphoma (FL). Those who were obese
      (body mass index >/= 30) were up to three times more likely to develop NHL or its
      major subtypes than persons with body mass index of 20 to <25. Obesity-related
      genetic factors including common polymorphisms in the leptin gene (LEP A19G and G
      2548A) and its receptor (LEPR Q223R) were investigated in DNA available for 376
      patients and 805 controls. Leptin is an adipocyte-derived hormone that regulates
      food intake and modulates immune and inflammatory responses through its receptor.
      Among those with the LEP 19G allele, an increased risk estimate was found for all
      NHL [OR = 1.6, confidence interval (CI) 1.1-2.3], DLCL (OR = 1.6, CI 0.86-3.0),
      and FL lymphoma (OR = 1.9, CI 0.98-3.6). Gene-gene interaction existed between
      the -G2548A and LEPR Q223R polymorphisms. Specifically, among those with LEPR
      223RR, the risk estimate for NHL was increased in LEP -2548GA (OR = 1.7, CI 0.88
      3.1) and LEP -2548AA (OR = 2.3,CI 1.1-4.6) relative to LEP -2548GG genotypes.
      These results suggest that genetic interactions between leptin and its receptor
      may promote immune dysfunction associated with obesity and NHL and that the
      emerging obesity epidemic is consistent with the increasing incidence of NHL in
      developed countries.

PMID- 15159311
TI  - Common gene polymorphisms in the metabolic folate and methylation pathway and the
      risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.
AB  - Folate and methionine metabolism is involved in DNA synthesis and methylation
      processes. Polymorphisms in the genes of folate metabolism enzymes have been
      associated with some forms of cancer. In a case-control study, we evaluated
      whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR
      C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase
      reductase (MTRR A66G) genes may have a role in altering susceptibility to adult
      acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed
      DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual
      carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds
      ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types.
      Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20,
      95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR
      677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR
      0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes
      revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally,
      those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL
      risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show
      any significant difference for all the polymorphisms investigated, but in the low
      grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG
      homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95%
      CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data
      are in accordance with the hypothesis that polymorphisms in the genes for folate
      and methionine metabolism might play a greater role in the occurrence of ALL than
      NHL by influencing DNA synthesis and/or DNA methylation.

PMID- 15159312
TI  - High-throughput association testing on DNA pools to identify genetic variants
      that confer susceptibility to acute myeloid leukemia.
AB  - We have evaluated the use of allele-specific PCR (AS PCR) on DNA pools as a tool
      for screening inherited genetic variants that may be associated with risk of
      adult acute myeloid leukemia (AML). Two DNA pools were constructed, one of 444
      AML cases, and another of 823 matched controls. The pools were validated using
      individual genotyping data for GSTP1 and LTalpha variants. Allele frequencies for
      variants in GSTP1 and LTalpha were estimated using quantitative AS PCR, and when
      compared to individual genotyping data, a high degree of concordance was seen. AS
      primer pairs were designed for nine candidate genetic variants in DNA repair and
      cell cycle/apoptotic regulatory genes, including Cyclin D1 [codon 870 splice site
      variant (A>G)]; BRCA1, P871L; ERCC2, K751Q; FAS -1377 (G>A); hMLH1 -93 (G>A) and
      V219I; p21, S31R; and the XRCC1 R194W and R399Q variants. For six of these
      assays, there was at least 95% concordance between AS PCR genotyping and an
      alternative approach carried out on individual samples. Furthermore, these six AS
      PCR assays all accurately estimated allele frequencies in the pools that had been
      calculated using individual genotyping data. A significant disease association
      was seen with AML for the -1377 variant in FAS (odds ratio 1.76, 95% confidence
      interval 1.26-2.44). These data suggest that quantitative AS PCR can be used as
      an efficient screening technique for disease associations of genetic variants in
      DNA pools made from case-control studies.

PMID- 15159313
TI  - Identifying functional genetic variants in DNA repair pathway using protein
      conservation analysis.
AB  - The role of DNA repair in initiation, promotion, and progression of malignancy
      suggests that variations in DNA repair genes confer altered cancer risk.
      Accordingly, DNA repair gene variants have been studied extensively in the
      context of cancer predisposition. Single nucleotide polymorphisms (SNPs) are the
      most common genetic variations in the human genome. A fraction of SNPs are
      located within the genes, which are likely to alter the gene expression and
      function. SNPs that change the encoded amino acid sequence of the proteins (non
      synonymous; nsSNPs) are potentially genetic disease determinant variations.
      However, as not all amino acid substitutions are supposed to lead to a change in
      protein function, it will be necessary to have a priori prediction and
      determination of the functional consequences of amino acid substitutions per se,
      and then together with other genetic and environmental factors to study their
      possible association with a trait. Here we report the analysis of nsSNPs in 88
      DNA repair genes and their functional evaluation based on the conservation of
      amino acids among the protein family members. Our analysis demonstrated that >30%
      of variants of DNA repair proteins are highly likely to affect the function of
      the proteins drastically. In this study, we have shown that three nsSNPs, which
      were predicted to have functional consequences (XRCC1-R399Q, XRCC3-T241M, XRCC1
      R280H), were already found to be associated with cancer risk. The strategy
      developed and applied in this study has the potential to identify functional
      protein variants of DNA repair pathway that may be associated with cancer
      predisposition.

PMID- 15159314
TI  - Assessment of polymorphic variants in the melanocortin-1 receptor gene with
      cutaneous pigmentation using an evolutionary approach.
AB  - The melanocortin-1 receptor gene (MC1R) encodes a membrane-bound receptor protein
      that is central to melanin synthesis. The coding region of MC1R is highly
      polymorphic and associations of variants with pigmentation phenotypes and risk
      for cutaneous neoplasms have been reported. We sought to determine the
      distribution and frequency of MC1R variants and their relationship to
      pigmentation characteristics in 179 Caucasian controls from the United States.
      One hundred thirty-five (75.4%) subjects carried one or more variants, and we
      determined that carriage of the previously designated "red hair color" (RHC)
      alleles, R151C, R160W, and D294H was strongly associated with fair pigmentation
      phenotypes including light hair and eye color, tendency to burn, decreased
      tendency to tan, and freckling. We used SIFT software to define MC1R protein
      positions that were predicted intolerant to amino acid substitutions; detected
      variants that corresponded to intolerant substitutions were D84E, R142H, R151C,
      I155T, R160W, and D294H. Carriage of one or more of these putative functionally
      important variants or the frameshift variant ins86A was significantly associated
      with fair pigmentation phenotypes. Analyses limited to carriage of ins86A and the
      three non-RHC alleles identified by SIFT were attenuated and no longer reached
      statistical significance. This is the first study to describe MC1R variants among
      control subjects from the U.S. Our results indicate that the frequency of
      variants is similar to that previously observed among non-U.S. Caucasians. Risk
      variants defined by either the published literature or by evolutionary criteria
      are strongly and significantly associated with all fair pigmentation phenotypes
      that were measured.

PMID- 15159315
TI  - Micronuclei as biomarkers of carcinogen exposure in populations exposed to
      arsenic through drinking water in West Bengal, India: a comparative study in
      three cell types.
AB  - Contamination of groundwater by arsenic, a paradoxical human carcinogen, has
      become a cause of global public health concern. In West Bengal, India, the
      groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various
      adverse health effects including cancer have been reported from these districts
      and are associated with prolonged arsenic exposure. A cross-sectional biomarker
      study was conducted to evaluate and compare the frequencies of micronuclei in
      peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the
      inhabitants of North 24 Parganas, one of the arsenic-affected districts. The
      three cell types were collected from 163 residents exposed to high levels of
      arsenic in drinking water (214.7213 +/- 9.0273 microg/l) and from 154 unexposed
      subjects residing in the unaffected East Midnapur district with very little or no
      exposure to arsenic through drinking water (9.2017 +/- 0.3157 microg/l). Our
      analysis revealed that micronuclei frequencies in the exposed group were
      significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63
      fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in
      micronuclei frequencies significant at P < 0.01). The results indicate that
      chronic ingestion of arsenic in drinking water by the exposed subjects is linked
      to the enhanced incidence of micronuclei in all the three cell types, slightly
      higher level of micronuclei being observed in lymphocytes compared with oral
      mucosa and urothelial cells.

PMID- 15159316
TI  - Myeloperoxidase (MPO) -463G->A reduces MPO activity and DNA adduct levels in
      bronchoalveolar lavages of smokers.
AB  - The myeloperoxidase (MPO) -463G-->A genetic polymorphism is associated with a
      reduced risk for lung cancer, but the underlying mechanism is not yet elucidated.
      Therefore, the impact of this polymorphism on MPO activity and lipophilic DNA
      adducts was studied in respectively bronchoalveolar lavage (BAL) fluid and cells,
      from 106 smoking Caucasian lung patients. MPO activity was determined
      spectrophotometrically, aromatic DNA adducts by (32)P-postlabeling and MPO
      genotypes by RFLP analysis. Frequencies of MPO -463AA (13%), MPO -463AG (36%),
      and MPO -463GG (51%) were in line with earlier observations. MPO
      activity/neutrophil was lower in MPO -463AA (median 0.04 pU/cell) than in MPO 
      463AG (median 0.07 pU/cell) and MPO -463GG (median 0.14 pU/cell; P = 0.059)
      individuals. DNA adducts in BAL cells were measured in 11 MPO -463AA subjects and
      equal numbers of MPO -463AG and MPO -463GG subjects matched for smoking, age,
      gender, and clinical diagnosis. DNA adduct levels in MPO -463AA individuals
      (median 0.62 adducts/10(8) nucleotides) were lower than in MPO -463AG (median
      1.51 adducts/10(8) nucleotides) and MPO -463GG (median 3.26 adducts/10(8)
      nucleotides; P = 0.003) subjects. Overall, no significant correlation was
      observed between amount of inhaled tar/day and DNA adduct levels. However,
      correlations improved considerably on grouping according to the MPO genotype; MPO
      -463AA subjects were the least responsive (R(2) = 0.73, slope = 0.4, P = 0.01)
      followed by MPO -463AG subjects (R(2) = 0.70, slope = 1.3, P = 0.01) and MPO 
      463GG patients (R(2) = 0.67, slope = 2.8, P = 0.02). These data demonstrate that
      MPO -463AA/AG genotypes are associated with (a) reduced MPO activity in BAL fluid
      and (b) reduced smoking-related DNA adduct levels in BAL cells in a gene-dose
      manner. These data provide a plausible biological explanation for the reduced
      risk for lung cancer as observed in MPO -463AA/AG compared with MPO -463GG
      subjects.

PMID- 15159317
TI  - Effects of reduced cigarette smoking on levels of 1-hydroxypyrene in urine.
AB  - We investigated the effects of smoking fewer cigarettes/day (CPD) on urinary
      levels of 1-hydroxypyrene (1-HOP), a biomarker of carcinogenic polycyclic
      aromatic hydrocarbon (PAH) uptake. We randomly assigned 151 smokers to either a
      reduction group or a waitlist group. In the reduction group, we measured urinary
      1-HOP at two baseline intervals. Then, the smokers were expected to reduce their
      CPD by 25% in weeks 0-2, 50% in weeks 2-4, and 75% in weeks 4-6 and to maintain
      reduced smoking through week 26. In the waitlist group, four baseline
      measurements were taken and then the smokers joined the reduction group. Urinary
      1-HOP was quantified at weeks 4, 6, 8, 12, and 26 after baseline. Statistically
      significant reductions in urinary 1-HOP were observed at most time points
      examined in groups of smokers who reduced to different extents. Reductions in the
      waitlist group were also generally significantly greater than baseline levels.
      The reductions in 1-HOP were usually modest (ranging from 14% to 35% in all
      groups and time points examined), which partially reflects the fact that there
      are sources of pyrene exposure other than cigarette smoke. Thus, cessation of
      smoking would only be expected to result in partial reductions of 1-HOP. The
      observed reductions in 1-HOP were not fully consistent with reductions in CPD
      probably due to uncontrolled dietary factors. Collectively, the results
      demonstrate that some smokers can achieve substantial reductions in 1-HOP,
      reflecting reduced uptake of polycyclic aromatic hydrocarbons, by reducing CPD,
      but there was not a consistent relationship between these parameters.

PMID- 15159318
TI  - Urinary excretion of flavonoids reflects even small changes in the dietary intake
      of fruits and vegetables.
AB  - BACKGROUND: Due to the random and systematic measurement errors associated with
      current dietary assessment instruments, there is a need to develop more objective
      methods of measuring the intake of foods of importance to human health.
      OBJECTIVE: The purpose of this study was to test whether urinary excretion of
      flavonoids could be used to identify subjects who are meeting Norwegian
      recommendations for fruit and vegetable intake (5 servings per day) from
      individuals who are consuming the national average amount of fruits and
      vegetables (2 servings per day). DESIGN: Twenty-four-hour urine samples were
      collected in a strict crossover controlled feeding study. Forty healthy subjects
      (19-34 years) were included in the study. After a 1-week run-in period, one group
      was given a controlled diet that included 2 servings (300 g) of fruits and
      vegetables daily for 14 days, while the other group was given a diet containing 5
      servings (750 g) per day. Following a 2-week washout and a 1 week run-in period,
      the regimens were switched between the groups. RESULTS: An increased intake of
      mixed fruits and vegetables from 2 to 5 servings per day significantly enhanced
      urinary excretion of eriodictyol, naringenin, hesperetin, quercetin, kaempferol,
      isorhamnetin, and tamarixetin. The citrus flavonoids naringenin and hesperetin
      showed a steep dose-response relationship to dietary intake of fruits and
      vegetables, whereas the association to eriodictyol, quercetin, kaempferol,
      isorhamnetin, and tamarixetin was more moderate. CONCLUSION: The present study
      indicates that urinary excretion of dietary flavonoids may be used to assess
      changes of mixed fruit and vegetable intake corresponding to an increase from the
      present national intake in Norway to the recommended amount of 5 servings of
      fruits and vegetables daily.

PMID- 15159319
TI  - Single-dose pharmacokinetic study of lycopene delivered in a well-defined food
      based lycopene delivery system (tomato paste-oil mixture) in healthy adult male
      subjects.
AB  - This report details the findings of a single-dose Phase I pharmacokinetic and
      toxicity study of a food-based formulation of lycopene in healthy adult male
      subjects. Five dosing groups (n = 5 per group) were sequentially treated with
      increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were
      collected for a total of 28 days (672 h) after administration of single doses of
      lycopene. The mean time (t(max)) to reach maximum total lycopene concentration
      (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between
      4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination
      half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201
      micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene
      exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to
      increments in dose, with larger increases observed at the lowest end of the
      dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h
      with the differences observed among the dosing groups not reaching statistical
      significance. These findings may reflect a process of absorption that is
      saturable at very low dosing levels or may be explained by the large
      interindividual variability in attained lycopene concentrations that were
      observed within each dosing group. Pharmacokinetic parameters for trans- and cis
      lycopene isomers were calculated and are reported here. The formulation was well
      tolerated with minimal side effects, which were mainly of gastrointestinal nature
      and of very low grade.

PMID- 15159320
TI  - Results of a phase I multiple-dose clinical study of ursodeoxycholic Acid.
AB  - BACKGROUND: The hydrophilic bile acid, ursodeoxycholic acid (UDCA), may
      indirectly protect against colon carcinogenesis by decreasing the overall
      proportion of the more hydrophobic bile acids, such as deoxycholic acid (DCA), in
      aqueous phase stool. In the AOM rat model, treatment with UDCA resulted in a
      significant decrease in adenoma formation and colorectal cancer. It was
      hypothesized that there is a dose-response relationship between treatment with
      the more hydrophilic bile acid, UDCA, and a reduction in the proportion of the
      more hydrophobic bile acid, DCA, in the aqueous stool phase, suggesting the
      potential of UDCA as a chemopreventive agent. METHODS: Eighteen participants were
      randomized to 300, 600, or 900 mg/day UDCA for 21 days in this multiple-dose,
      double-blinded study. Seventy-two-hour stool samples were collected pretreatment
      and on days 18-20 of UDCA treatment for bile acid measurements. Pharmacokinetics
      were performed and blood bile acids were measured at days 1 and 21 of UDCA
      treatment. RESULTS: There were no serious adverse events associated with UDCA
      treatment. There was a dose-response increase in the posttreatment to baseline
      ratio of UDCA to DCA from the 300 mg/day to the 600 mg/day group, but not between
      the 600 and the 900 mg/day groups, in both aqueous and solid phase stool. This
      posttreatment increase was statistically significant in aqueous phase stool for
      the 300 and 600 mg/day treatment groups (P = 0.038 and P = 0.014, respectively),
      but was only marginally significant in the 900 mg/day treatment group (P =
      0.057). Following the first dose administration, a dose-dependent increase in
      plasma ursodeoxycholic concentrations was observed in fasting subjects; however,
      when these levels were measured postprandially following 3 weeks of treatment,
      the areas under the plasma concentration-time profile (AUC) were not
      statistically different and remained relatively unchanged over time. CONCLUSIONS:
      UDCA treatment did not decrease the quantity of DCA in fecal water or solids;
      however, it did decrease the proportion of DCA in fecal water and solids in
      relation to UDCA. Thus, 3 weeks of UDCA treatment resulted in an overall increase
      in hydrophilicity of bile acids in the aqueous phase stool, with a peak effect
      observed with a daily dose of 600 mg/day. Much larger studies are needed to
      determine the effect of ursodeoxycholic administration on deoxycholic
      concentration, overall hydrophilicity of stool bile acids, and the long-term
      effects on intermediate biomarkers of cellular damage.

PMID- 15159321
TI  - Effects of a moderate intensity exercise intervention on estrogen metabolism in
      postmenopausal women.
AB  - Physical activity has been associated with reduced breast cancer risk,
      potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone
      (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) also has been
      associated with reduced breast cancer risk. Studies suggest that body composition
      and exercise can influence estrogen metabolism. We determined the effects of a 12
      month moderate intensity aerobic exercise intervention on urinary 2-OH E(1),
      16alpha-OH E(1), and their ratio in overweight and obese, previously sedentary,
      postmenopausal women, ages 50-75 years. Women were randomized to a 12-month
      exercise intervention (n = 87) or stretching control group (n = 86); 170
      completed the study. Urinary 2- and 16alpha-OH E(1) were measured in spot urines
      collected at baseline, 3, and 12 months. Body composition was measured at
      baseline and 12 months. Differences between exercisers and controls for excretion
      of estrogen metabolites were determined using general estimating equations.
      Further analyses assessed change in estrogen metabolites and their ratio by
      subgroups of change in body composition. Overall, there were no significant
      effects of the exercise intervention on 2-OH E(1), 16alpha-OH E(1), or their
      ratio (P > 0.05). There appeared to be an effect of change in intra-abdominal fat
      and adherence to the exercise intervention on change in the estrogen metabolites
      or their ratio. However, this did not reflect a potentially desirable change in
      estrogen metabolites associated with the exercise intervention. Thus, this 12
      month moderate intensity exercise intervention did not significantly alter
      urinary excretion of 2-OH E(1), 16alpha-OH E(1), or their ratio in this
      population of women.

PMID- 15159322
TI  - Predictors of participation in psychosocial telephone counseling following
      genetic testing for BRCA1 and BRCA2 mutations.
AB  - Although adjunctive educational and psychosocial programs are now being developed
      for BRCA1 and BRCA2 (BRCA1/2) mutation carriers, limited information is available
      about whether mutation carriers will want to receive such programs or about the
      characteristics of individuals who participate. The goals of the present study
      were to describe rates of completing a psychosocial telephone counseling (PTC)
      intervention that was offered to female BRCA1/2 mutation carriers and to identify
      sociodemographic and psychological factors associated with decisions to complete
      the intervention. Subjects were 66 BRCA1/2 mutation carriers who were randomized
      to receive a PTC intervention following receipt of genetic test results.
      Sociodemographic and psychological factors were evaluated before notification of
      assignment to the PTC intervention. Completion of the intervention was determined
      from study records. Overall, 75.8% of subjects completed the PTC intervention.
      Compared to unaffected subjects, those affected with breast and/or ovarian cancer
      were 76% less likely to complete the intervention [odds ratio (OR) = 0.24, 95%
      confidence interval (CI) = 0.06, 0.98, P = 0.05]. In addition, subjects with
      higher levels of cancer-specific distress [OR = 4.74, 95% CI = 1.02, 22.03, P =
      0.05] and those with greater perceptions of social support [OR = 5.81, 95% CI =
      1.29, 26.16, P = 0.02] were also most likely to complete the intervention. The
      results of this study suggest that while most BRCA1/2 mutation carriers are
      likely to complete an adjunctive psycho-educational program, personal history of
      cancer, cancer-specific distress, and perceptions of social support are likely to
      influence participation.

PMID- 15159323
TI  - Methylated DNA collected by tampons--a new tool to detect endometrial cancer.
AB  - This proof of principle study aimed to define a new and simple strategy for
      detection of endometrial cancer using epigenetic markers. We investigated DNA
      isolated from vaginal secretion collected from tampon for aberrant methylation of
      five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15
      patients with endometrial cancer and 109 patients without endometrial cancer. All
      endometrial cancer patients revealed three or more methylated genes, whereas 91%
      (99 of 109) of the patients without endometrial cancer had no or fewer than three
      genes methylated in their vaginal secretion. The methods developed in this study
      provide the basis for a prospective clinical trial to screen asymptomatic women
      who are at high risk for endometrial cancer.

PMID- 15159325
TI  - Exercise-induced premature ventricular beats: should we do anything differently?

PMID- 15159324
TI  - Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps.
AB  - Two isoforms of prostaglandin H synthase (PTGS = COX) are key enzymes in
      prostaglandin synthesis and primary targets for aspirin and other non-steroidal
      anti-inflammatory drugs (NSAIDs). Use of aspirin or other NSAIDs is associated
      with a lower risk and reduced recurrence of colorectal adenomas, established
      precursors of adenocarcinoma. This study investigated risk of colorectal
      adenomatous and hyperplastic polyps associated with several polymorphisms in the
      coding region of PTGS1. Within the Minnesota polyp case-control study, patients
      with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n =
      621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15
      L16del, P17L, L237M); these had been predicted to affect protein function based
      on sequence-homology software. Age- and sex-adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) were computed. Whereas there was no appreciable
      difference in adenoma or hyperplastic polyp risk associated with R8W, P17L, and
      L237M, an increased risk was observed for individuals heterozygous for the L15
      L16del polymorphism (OR = 3.6, 95% CI 1.2-11.2). The variant L15-L16del allele
      appeared to be associated with a stronger increase in adenoma risk among nonusers
      of aspirin/other NSAIDs. The reduced risk observed with aspirin/other NSAID use
      was limited to those wild type for P17L [PP users: OR = 0.6 (0.5-0.8) versus PP
      nonusers: 1.0 (referent) (P interaction = 0.03)]. To our knowledge, this study
      represents the first investigation of polymorphisms in PTGS1 and risk of
      colorectal polyps. The L15-L16del variant allele may result in an increased risk
      of colorectal adenomas, whereas P17L may be relevant to the pharmacogenetics of
      aspirin. These preliminary findings require confirmation in larger studies of
      colorectal neoplasia.

PMID- 15159326
TI  - Specialization and its discontents: the pernicious impact of regulations against
      specialization and physician ownership on the US healthcare system.

PMID- 15159327
TI  - Evolution of the American hospital system: subspecialization and physician
      ownership.

PMID- 15159328
TI  - Doctors and hospitals: healthcare's Rubik's cube.

PMID- 15159329
TI  - Molecular and cell-based therapies for protection, rescue, and repair of ischemic
      myocardium: reasons for cautious optimism.

PMID- 15159330
TI  - Mutation in the KCNQ1 gene leading to the short QT-interval syndrome.
AB  - BACKGROUND: The electrocardiographic short QT-interval syndrome forms a distinct
      clinical entity presenting with a high rate of sudden death and exceptionally
      short QT intervals. The disorder has recently been linked to gain-of-function
      mutation in KCNH2. The present study demonstrates that this disorder is
      genetically heterogeneous and can also be caused by mutation in the KCNQ1 gene.
      METHODS AND RESULTS: A 70-year man presented with idiopathic ventricular
      fibrillation. Both immediately after the episode and much later, his QT interval
      was abnormally short without any other physical or electrophysiological
      anomalies. Analysis of candidate genes identified a g919c substitution in KCNQ1
      encoding the K+ channel KvLQT1. Functional studies of the KvLQT1 V307L mutant
      (alone or coexpressed with the wild-type channel, in the presence of IsK)
      revealed a pronounced shift of the half-activation potential and an acceleration
      of the activation kinetics leading to a gain of function in I(Ks). When
      introduced in a human action potential computer model, the modified biophysical
      parameters predicted repolarization shortening. CONCLUSIONS: We present an
      alternative molecular mechanism for the short QT-interval syndrome. Functional
      and computational studies of the KCNQ1 V307L mutation identified in a patient
      with this disorder favor the association of short QT with mutation in KCNQ1.

PMID- 15159331
TI  - Images in cardiovascular medicine. Left ventricular pseudoaneurysm: clinical role
      of cardiovascular magnetic resonance imaging.

PMID- 15159332
TI  - Exercise capacity and the risk of death in women.

PMID- 15159333
TI  - Insulin sensitivity, glucose metabolism, and membrane fluidity in hypertensive
      subjects.

PMID- 15159334
TI  - Cardiac memory and cortical memory.

PMID- 15159335
TI  - Proximal aortic diameter and aortic pressure-flow relationship in systolic
      hypertension.

PMID- 15159336
TI  - Extracorporeal membrane oxygenation support for acute pulmonary embolism.

PMID- 15159341
TI  - Medicare on the hustings.

PMID- 15159337
TI  - Clopidogrel-atorvastatin interaction.

PMID- 15159344
TI  - Discontinuation of benzodiazepines.

PMID- 15159345
TI  - Recognizing neuroleptic malignant syndrome.

PMID- 15159346
TI  - Cat naps.

PMID- 15159347
TI  - Discontinuation of benzodiazepines.

PMID- 15159348
TI  - Sustainability of health care in Canada.

PMID- 15159349
TI  - Sustainability of health care in Canada.

PMID- 15159350
TI  - Reducing adverse events.

PMID- 15159352
TI  - ED problems result of bed shortages, doctors contend.

PMID- 15159354
TI  - Breast cancer patients sue over radiotherapy wait times.

PMID- 15159356
TI  - Cesarean sections at all-time high.

PMID- 15159357
TI  - US adopts bar codes for drug products.

PMID- 15159358
TI  - Responding to tragic error: lessons from Foothills Medical Centre.

PMID- 15159359
TI  - Is a perfect storm brewing on the health care front?

PMID- 15159360
TI  - Prevention of osteoporosis and osteoporotic fractures in postmenopausal women:
      recommendation statement from the Canadian Task Force on Preventive Health Care.

PMID- 15159361
TI  - Asthma drug zafirlukast (Accolate): serious hepatic events.

PMID- 15159362
TI  - West Nile virus: round five.

PMID- 15159364
TI  - Sturge-Weber syndrome diagnosed in a 45-year-old man.

PMID- 15159365
TI  - Relation between randomized controlled trials published in leading general
      medical journals and the global burden of disease.
AB  - BACKGROUND: More than two-thirds of the world's population live in low-income
      countries, where health priorities are different from those of people living in
      more affluent parts of the world. We evaluated the relation between the global
      burden of disease and conditions or diseases studied in randomized controlled
      trials (RCTs) published in general medical journals. METHODS: A MEDLINE search
      identified 373 RCTs that had been published in 6 international peer-reviewed
      general medical journals in 1999. Manual review excluded non-RCTs, brief reports
      and trials in which the unit of randomization was not the patient; 286 RCTs
      remained eligible for analysis. We identified the RCTs that studied any of the 40
      leading causes of the global burden of disease. Five of these conditions were
      considered unsuitable for study with an RCT design and were excluded from
      subsequent analysis. To provide a practical perspective, we asked 12 experts
      working with international health organizations to rate the relevance to global
      health of the articles that studied any of the top 10 causes of the global burden
      of disease, as measured by disability-adjusted life years (DALYs) and mortality,
      using a 5-point Likert scale. RESULTS: Among the 286 RCTs in our sample, 124
      (43.4%) addressed 1 of the 35 leading causes of the global burden of disease. Of
      these, ischemic heart disease, HIV/AIDS and cerebrovascular disease were the most
      commonly studied conditions. Ninety articles (31.5%) studied 1 of the top 10
      causes of the global burden of disease. The mean rating (and standard deviation)
      for international health relevance assigned by experts was 2.6 (1.5) out of 5.
      Only 14 (16%) of the 90 trials received a rating of 4 or greater, indicating high
      relevance to international health. Almost half of the 40 leading causes of the
      global burden of disease were not studied by any trial. INTERPRETATION: Many
      conditions or diseases common internationally are underrepresented in RCTs
      published in leading general medical journals. Trials published in these journals
      that studied one of these high-priority conditions were generally rated as being
      of little relevance to international health.

PMID- 15159366
TI  - The Canadian Adverse Events Study: the incidence of adverse events among hospital
      patients in Canada.
AB  - BACKGROUND: Research into adverse events (AEs) has highlighted the need to
      improve patient safety. AEs are unintended injuries or complications resulting in
      death, disability or prolonged hospital stay that arise from health care
      management. We estimated the incidence of AEs among patients in Canadian acute
      care hospitals. METHODS: We randomly selected 1 teaching, 1 large community and 2
      small community hospitals in each of 5 provinces (British Columbia, Alberta,
      Ontario, Quebec and Nova Scotia) and reviewed a random sample of charts for
      nonpsychiatric, nonobstetric adult patients in each hospital for the fiscal year
      2000. Trained reviewers screened all eligible charts, and physicians reviewed the
      positively screened charts to identify AEs and determine their preventability.
      RESULTS: At least 1 screening criterion was identified in 1527 (40.8%) of 3745
      charts. The physician reviewers identified AEs in 255 of the charts. After
      adjustment for the sampling strategy, the AE rate was 7.5 per 100 hospital
      admissions (95% confidence interval [CI] 5.7- 9.3). Among the patients with AEs,
      events judged to be preventable occurred in 36.9% (95% CI 32.0%-41.8%) and death
      in 20.8% (95% CI 7.8%-33.8%). Physician reviewers estimated that 1521 additional
      hospital days were associated with AEs. Although men and women experienced equal
      rates of AEs, patients who had AEs were significantly older than those who did
      not (mean age [and standard deviation] 64.9 [16.7] v. 62.0 [18.4] years; p =
      0.016). INTERPRETATION: The overall incidence rate of AEs of 7.5% in our study
      suggests that, of the almost 2.5 million annual hospital admissions in Canada
      similar to the type studied, about 185 000 are associated with an AE and close to
      70 000 of these are potentially preventable.

PMID- 15159367
TI  - Evidence for global health.

PMID- 15159368
TI  - Health care as a risk factor.

PMID- 15159369
TI  - Malaria.
AB  - Malaria is a parasitic infection of global importance. Although relatively
      uncommon in developed countries, where the disease occurs mainly in travellers
      who have returned from endemic regions, it remains one of the most prevalent
      infections of humans worldwide. In endemic regions, malaria is a significant
      cause of morbidity and mortality and creates enormous social and economic
      burdens. Current efforts to control malaria focus on reducing attributable
      morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated
      bed nets have been successful in some endemic areas. For travellers to malaria
      endemic regions, personal protective measures and appropriate chemoprophylaxis
      can significantly reduce the risk of infection. Prompt evaluation of the febrile
      traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis,
      and appropriate antimalarial therapy are essential in order to optimize clinical
      outcomes of infected patients. Additional approaches to malaria control,
      including genetic manipulation of mosquitoes and malaria vaccines, are areas of
      ongoing research.

PMID- 15159375
TI  - Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed
      lymph nodes through high endothelial venules.
AB  - Recruitment of dendritic cells (DCs) to lymph nodes (LNs) is pivotal to the
      establishment of immune response. Whereas DCs have been proven to undergo
      afferent lymphatic pathway to enter LNs from peripheral tissues, a question
      remains if DCs also migrate into LNs directly from the circulation. Here we
      demonstrate that plasmacytoid DC (pDC) precursors can transmigrate across high
      endothelial venules (HEVs) of inflamed LNs in mice. Bacterial infection induces a
      significant number of pDC and myeloid DC (mDC) precursors into the circulation.
      Both subsets express a common set of chemokine receptors except CXCR3, display
      parallel mobilization into the blood, but show distinct trafficking pathway to
      the LNs. In a short-term homing assay, whereas mDC precursors migrate to
      peripheral tissues and subsequently to draining LNs, pDC precursors directly
      enter the LNs in a CXCL9 and E-selectin dependent manner. Tumor necrosis factor
      alpha controls not only DC precursor mobilization into the blood but also
      chemokine up-regulation on LN HEVs. A similar trafficking pathway is observed
      also in viral infection, and CXCR3(-/-) mice-derived pDC precursors show
      defective trans-HEV migration. This study clarifies the inflammation-dependent,
      chemokine-driven distinct property of DC precursor trafficking.

PMID- 15159376
TI  - Autoantibodies purified from therapeutic preparations of intravenous
      immunoglobulins (IVIg) induce the formation of autoimmune complexes in normal
      human serum: a role in the in vivo mechanisms of action of IVIg?
AB  - Although intravenous immunoglobulins (IVIg) are widely used in the treatment of
      many autoimmune and inflammatory diseases, the mechanisms of action are still
      unclear in most cases. We have recently reported the presence of soluble
      autoimmune complexes (auto-IC) in human serum after the addition of a dose of
      IVIg similar to the one used in therapy. Here, we report the isolation and
      characterization of the responsible auto-IgG present in IVIg. The auto-IgG were
      purified by affinity chromatography on serum proteins immobilized on Sepharose.
      The purified auto-IgG constituted approximately 3% of the IgG present in IVIg and
      recognized a wide variety of structures in ELISA as well as many serum proteins
      on western blots. Auto-IC were formed in human serum following the addition of an
      amount of purified auto-IgG sufficient to over-saturate the auto-IgG inhibitory
      mechanisms known to be present in normal serum. These results indicate that most
      of the IgG present in IVIg are not involved in the formation of the soluble auto
      IC, raising the possibility of preparing from IVIg a novel product which could be
      used for the treatment of the autoimmune diseases in which IC are thought to play
      an important role.

PMID- 15159377
TI  - Determining virological, serological and immunological parameters of EBV
      infection in the development of PTLD.
AB  - Post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)
      seronegative solid organ transplant recipients remains a significant problem,
      particularly in the first year post-transplant. Immune monitoring of a cohort of
      high-risk patients indicated that four EBV seronegative transplant recipients
      developed early-onset PTLD prior to evidence of an EBV humoral response. EBV
      status has been classically defined serologically, however these patients
      demonstrated multiple parameters of EBV infection, including the generation of
      EBV-specific CTL, outgrowth of spontaneous lymphoblastoid cell lines, and
      elevated EBV DNA levels, despite the absence of a classic EBV antibody response.
      As EBV serology is influenced by both immunosuppression and cytomegalovirus
      immunoglobulin treatment, both the EBV-specific CTL response and elevated EBV
      levels are more reliable indicators of EBV infection post-transplant.

PMID- 15159378
TI  - An increased frequency of autoantibody-inducing CD4+ T cells in pre-diseased
      lupus-prone mice.
AB  - Pathogenic autoantibody production in murine models of lupus is dependent on
      autoreactive CD4+ helper T cells. However, the mechanisms which permit the
      selection and maintenance of this autoantibody-inducing CD4+ T-cell repertoire
      are currently unknown. We hypothesized that the peripheral CD4+ T-cell repertoire
      of lupus-prone mice was enriched with autoantibody-inducing specificities. To
      test this, we utilized the splenic focus assay to determine if pre-diseased lupus
      prone (NZB x NZW)F(1) mice have an elevated frequency of autoreactive CD4+ T
      lymphocytes capable of supporting autoantibody production. The splenic focus
      limiting dilution assay permits anti-nuclear antibodies to be generated from
      contact-dependent T-B interactions in vitro. We show that young, pre-diseased
      lupus-prone mice have an elevated frequency of autoantibody-inducing CD4+ T
      cells. Interestingly, these autoantibody-inducing CD4+ T-cell responses are also
      present in the thymus. Therefore, an elevated frequency of autoantibody-inducing
      CD4+ T cells predisposes lupus-prone mice to the development of autoantibodies.

PMID- 15159379
TI  - Tempol attenuates excitatory actions of angiotensin II in the rostral
      ventrolateral medulla during emotional stress.
AB  - Superoxide has been shown to be an important intracellular mediator of actions of
      angiotensin II. Recently, we found that blockade of angiotensin II type-1
      receptors in the rostral ventrolateral medulla (RVLM) abrogated the pressor
      effect of emotional stress in rabbits. In the present study, we examined the
      influence of superoxide dismutase mimetics, tempol and tiron, in RVLM on
      cardiovascular stress response in conscious rabbits. Air-jet stress evoked a
      sustained increase in blood pressure (+14+/-2 mm Hg), tachycardia (+52+/-7 bpm),
      and renal sympathoactivation (+58+/-8%). Bilateral microinjections of tempol or
      tiron (20 nmol) into RVLM did not alter resting cardiovascular parameters, but
      attenuated the pressor, sympathetic, and tachycardiac response to stress by 40%
      to 55%. By contrast, 3-carbamoylproxyl, which is structurally close to tempol but
      has a lower superoxide scavenging activity, did not alter the stress response.
      Neither tempol nor tiron altered the sympathoexcitatory response to glutamate
      microinjections into RVLM or to baroreceptor unloading. Microinjections of nitric
      oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10 nmol)
      into RVLM did not affect the stress response. Coinjections of tempol and L-NAME
      decreased the pressor response to stress by 35+/-3%. Tempol attenuated the
      pressor response to microinjection of angiotensin II into RVLM by 59+/-15%,
      whereas L-NAME did not alter this response. These results suggest that superoxide
      dismutase mimetics in RVLM attenuate, partially via a nitric oxide-independent
      mechanism, the pressor effect of emotional stress in rabbits. Together with our
      previous studies, these results also indicate that superoxide is a key mediator
      of excitatory actions of angiotensin II in RVLM during acute stress.

PMID- 15159380
TI  - Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female
      rats.
AB  - Postmenopausal estrogen deficiency increases the incidence of cerebrovascular
      disease. However, hormone replacement therapy is associated with an increased
      cardiovascular risk. Tamoxifen is a selective estrogen receptor modulator with
      estrogenic effects on cardiovascular risk factors, but its long-term impacts on
      cerebral vasculature are unknown. We hypothesized that chronic 17beta-estradiol
      or tamoxifen treatment exerted similar effects in reducing cerebrovascular
      tension in ovariectomized rats. We therefore determine whether (1) chronic 17beta
      estradiol treatment could influence vasomotor activities, (2) chronic tamoxifen
      therapy could exert an estrogen-like or estrogen-antagonistic effect, and (3)
      acute exposure to estrogen could mimic the effect of 17beta-estradiol. Isometric
      tension was measured in cerebral arteries from female rat groups: control,
      ovariectomy, ovariectomy plus 17beta-estradiol treatment, ovariectomy plus
      tamoxifen treatment, and ovariectomized rats treated with tamoxifen and 17beta
      estradiol. Ovariectomy enhanced cerebrovascular contractions to endothelin-1 or
      CaCl2, but not to U46619 or phenylephrine. 17beta-Estradiol therapy reversed
      these effects. Chronic tamoxifen treatment exerted estrogen-like actions by
      reversing ovariectomy-induced enhancement of vessel tone without antagonizing the
      effect of chronic 17beta-estradiol treatment. Ovariectomy enhanced the relaxing
      potency of nicardipine, and 17beta-estradiol treatment prevented this effect.
      Acute exposure to 10(-9) mol/L 17beta-estradiol or 10(-8) mol/L tamoxifen did not
      modulate contractions in rings from nonoperated female rats. In conclusion,
      ovariectomy differentially enhances agonist-induced cerebrovascular tone, an
      effect that was reversed by estrogen therapy. Tamoxifen does not act as an
      estrogen antagonist; instead, it functions as an estrogen agonist during estrogen
      deficiency. Thus, tamoxifen may confer beneficial effects similar to estrogen in
      cerebrovascular vessels.

PMID- 15159381
TI  - Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia
      Aging Study.
AB  - Hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and
      neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to
      global ischemia, which may lead to atrophy. We investigated the association of
      midlife blood pressure (BP) and late-life HA in a sample of Japanese-American men
      born between 1900 and 1919. BP was measured on 3 occasions between 1965 and 1971.
      In 1994 to 1996 a subsample underwent magnetic resonance imaging (MRI) of the
      brain. Hippocampal volume was estimated by manually drawing regions of interest
      on relevant scan slices; HA was defined as the lowest quartile of hippocampal
      volume. Also assessed on the MRI were cortical and subcortical infarcts, lacunes,
      and white matter hyperintensities. The risk (OR, 95% CI) was estimated for HA
      associated with systolic (<140 versus > or =140 mm Hg) and diastolic (<90 versus
      > or =90 mm Hg) BP and with antihypertensive treatment. Analyses were adjusted
      for sociodemographic factors, other cardiovascular risk factors, apolipoprotein E
      allele, and correlated brain pathology. Those never treated with antihypertensive
      medication had a significantly increased risk for HA (OR 1.7; CI=1.12; 2.65). The
      nontreated subjects with high systolic BP had an increased risk (OR=1.98;
      CI=0.89; 4.39) for HA. Results were similar for untreated men with high diastolic
      BP (OR=3.51; CI=1.26; 9.74). In conclusion, treatment with antihypertensive
      treatment modifies the association of BP and HA, such that high levels of BP
      adversely affect the hippocampus in persons never treated with antihypertensives.

PMID- 15159382
TI  - Full structural characterization of the lipid A components from the Agrobacterium
      tumefaciens strain C58 lipopolysaccharide fraction.
AB  - For the first time, the complete structure of the lipid A from the
      lipopolysaccharide of an Agrobacterium species is here reported. In particular,
      the structure of the lipid A from A. tumefaciens strain C58, a soil pathogen
      bacterium strictly related to Rhizobiaceae, was determined. The structural study,
      carried out by chemical analysis, mass spectrometry, and nuclear magnetic
      resonance spectroscopy, revealed that lipid A fraction consisted of a mixture of
      species all sharing the bis-phosphorylated glucosamine disaccharide backbone that
      could be designated in two main structural motifs, according to the acylation
      pattern. The main species was a penta-acylated lipid A bearing two unsubstituted
      14:0 (3-OH) fatty acids in ester linkage and two 16:0 (3-OH) in amide linkage;
      the one on GlcN II was O-acylated by a long chain fatty acid, 28:0 (27-OH). This
      in turn was esterified by a 3-hydroxy-butyroyl residue at its hydroxy group. The
      second species, in lesser amounts, was identified as a tetra-acylated lipid A and
      lacked the 14:0 (3-OH) residue on GlcN I. Other species deriving from these two
      lacked a phosphate group or 3-hydroxy-butyroyl residue or otherwise carried a
      26:0 (25-OH) as long chain fatty acid. The lipid A structure of phytopathogen A.
      tumefaciens strain C58 presents deep structural analogies with lipid A of
      symbiotic Rhizobium, and the hypothesis is advanced that it can be a strategy of
      the bacterium to escape or attenuate the plant response.

PMID- 15159383
TI  - Structural characterization by (13)C-NMR spectroscopy of products synthesized in
      vitro by polysaccharide synthases using (13)C-enriched glycosyl donors:
      application to a UDP-glucose:(1-->3)-beta-D-glucan synthase from blackberry
      (Rubus fruticosus).
AB  - A simple and sensitive method for the characterization of products synthesized in
      vitro by polysaccharide synthases is described. It relies on the use of (13)C
      enriched nucleotide sugars as substrates and on the analysis of the newly
      synthesized polysaccharides by (13)C-nuclear magnetic resonance (NMR)
      spectroscopy. The method was validated with a (1-->3)-beta-d-glucan synthase from
      blackberry, but it may be applied to the study of any glycosyltransferase. The
      chemical synthesis of UDP-d-[U-(13)C]glucose was achieved in a classical
      procedure with an overall yield of 50%. A uniformly labeled (1-->3)-beta-d-glucan
      was synthesized from this substrate, using detergent extracts of blackberry cell
      membranes as a source of synthase. One hundred micrograms of product was
      sufficient for liquid and solid-state (13)C-NMR spectroscopy analyses. The method
      is at least 100 times more sensitive than in the case of nonenriched
      polysaccharides. It allows the unequivocal identification and direct structural
      characterization of the products synthesized in vitro, as opposed to conventional
      methods that rely on the use of radioactive substrates and enzymatic hydrolysis
      of the polysaccharides with specific glycoside hydrolases. The method proves that
      the glycan analyzed was synthesized de novo because the final product is enriched
      in (13)C. Information on the 3D organization of the polymer may also be obtained
      by solid-state NMR spectroscopy.

PMID- 15159384
TI  - A homolog of prokaryotic thiol disulfide transporter CcdA is required for the
      assembly of the cytochrome b6f complex in Arabidopsis chloroplasts.
AB  - The c-type cytochromes are defined by the occurrence of heme covalently linked to
      the polypeptide via thioether bonds between heme and the cysteine sulfhydryls in
      the CXXCH motif of apocytochrome. Maintenance of apocytochrome sulfhydryls in a
      reduced state is a prerequisite for covalent ligation of heme to the CXXCH motif.
      In bacteria, a thiol disulfide transporter and a thioredoxin are two components
      in a thio-reduction pathway involved in c-type cytochrome assembly. We have
      identified in photosynthetic eukaryotes nucleus-encoded homologs of a prokaryotic
      thiol disulfide transporter, CcdA, which all display an N-terminal extension with
      respect to their bacterial counterparts. The extension of Arabidopsis CCDA
      functions as a targeting sequence, suggesting a plastid site of action for CCDA
      in eukaryotes. Using PhoA and LacZ as topological reporters, we established that
      Arabidopsis CCDA is a polytopic protein with within-membrane strictly conserved
      cysteine residues. Insertional mutants in the Arabidopsis CCDA gene were
      identified, and loss-of-function alleles were shown to impair photosynthesis
      because of a defect in cytochrome b(6)f accumulation, which we attribute to a
      block in the maturation of holocytochrome f, whose heme binding domain resides in
      the thylakoid lumen. We postulate that plastid cytochrome c maturation requires
      CCDA, thioredoxin HCF164, and other molecules in a membrane-associated trans
      thylakoid thiol-reducing pathway.

PMID- 15159385
TI  - Identification of HAX-1 as a protein that binds bile salt export protein and
      regulates its abundance in the apical membrane of Madin-Darby canine kidney
      cells.
AB  - ATP-binding cassette (ABC)-type proteins are essential for bile formation in
      vertebrate liver. BSEP, MDR1, MDR2, and MRP2 ABC transporters are targeted to the
      apical (canalicular) membrane of hepatocytes where they execute ATP-dependent
      transport of bile acids, drugs, amphipathic cations, phospholipids, and
      conjugated organic anions, respectively. Changes in activity and abundance of
      transporters in the canalicular membrane regulate bile flow; however, little is
      known regarding cellular proteins that bind ABC transporters and regulate their
      trafficking. A yeast two-hybrid screen identified HAX-1 as a binding partner for
      BSEP, MDR1, and MDR2. The interactions were validated biochemically by
      glutathione S-transferase pull-down and co-immunoprecipitation assays. BSEP and
      HAX-1 were over-represented in rat liver subcellular fractions enriched for
      canalicular membrane vesicles, microsomes, and clathrin-coated vesicles. HAX-1
      was bound to BSEP, MDR1, and MDR2 in canalicular membrane vesicles and co
      localized with BSEP and MDR1 in the apical membrane of Madin-Darby canine kidney
      (MDCK) cells. RNA interference of HAX-1 increased BSEP levels in the apical
      membrane of MDCK cells by 71%. Pulse-chase studies indicated that HAX-1 depletion
      did not affect BSEP translation, post-translational modification, delivery to the
      plasma membrane, or half-life. HAX-1 depletion resulted in an increased peak of
      metabolically labeled apical membrane BSEP at 4 h and enhanced retention at 6 and
      9 h. HAX-1 also interacts with cortactin. Expression of dominant negative
      cortactin increased steady state levels of BSEP 2-fold in the apical membrane of
      MDCK cells, as did expression of dominant negative EPS15. These findings suggest
      that HAX-1 and cortactin participate in BSEP internalization from the apical
      membrane.

PMID- 15159386
TI  - Regulation of penicillin G acylase gene expression in Escherichia coli by
      repressor PaaX and the cAMP-cAMP receptor protein complex.
AB  - The pga gene of Escherichia coli W ATCC11105 encodes a penicillin G acylase whose
      expression is regulated at both the transcriptional and post-transcriptional
      level. In this work we have shown that PaaX is the repressor of pga expression,
      and we have identified its binding consensus as TGATTC(N27)GAATCA. We conclude
      that the process of "PAA induction" actually involves relief of pga from
      repression by PaaX. Other features of the pga promoter have also been
      characterized. (i) It has a native class III cAMP-receptor protein (CRP)
      dependent promoter with two CRP-binding sites. (ii) The downstream CRP-binding
      site II has higher affinity. (iii) Binding of cAMP-CRP to both sites (I + II) is
      required for maximal expression. We have also shown that the PaaX-binding site
      overlaps with the CRP-binding site I. This implies that PaaX and the cAMP-CRP
      compete for binding to the region around the CRP-binding site I and therefore
      have antagonistic effects on pga expression.

PMID- 15159387
TI  - Genetic complementation between mutant b subunits in F1F0 ATP synthase.
AB  - In Escherichia coli, a parallel homodimer of identical b subunits constitutes the
      peripheral stalk of F(1)F(0) ATP synthase. Although the two b subunits have long
      been viewed as a single functional unit, the asymmetric nature of the enzyme
      complex suggested that the functional roles of each b subunit should not
      necessarily be considered equivalent. Previous mutagenesis studies of the
      peripheral stalk suffered from the fact that mutations in the uncF(b) gene
      affected both of the b subunits. We developed a system to express and study
      F(1)F(0) ATP synthase complexes containing two different b subunits. Two
      mutations already known to inactivate the F(1)F(0) ATP synthase complex have been
      studied using this experimental system. An evolutionarily conserved arginine,
      b(Arg-36), was known to be crucial for F(1)F(0) ATP synthase function, and the
      last four C-terminal amino acids had been shown to be important for enzyme
      assembly. Experiments expressing one of the mutants with a wild type b subunit
      demonstrated the presence of heterodimers in F(1)F(0) ATP synthase complexes.
      Activity assays suggested that the heterodimeric F(1)F(0) complexes were
      functional. When the two defective b subunits were expressed together and in the
      absence of any wild type b subunit, an active F(1)F(0) ATP synthase complex was
      assembled. This mutual complementation between fully defective b subunits
      indicated that each of the two b subunits makes a unique contribution to the
      functions of the peripheral stalk, such that one mutant b subunit is making up
      for what the other is lacking.

PMID- 15159388
TI  - Combined mutation of catalytic glutamate residues in the two nucleotide binding
      domains of P-glycoprotein generates a conformation that binds ATP and ADP
      tightly.
AB  - Combined mutation of "catalytic carboxylates" in both nucleotide binding domains
      (NBDs) of P-glycoprotein generates a conformation capable of tight binding of 8
      azido-ADP (Sauna, Z. E., Muller, M., Peng, X. H., and Ambudkar, S. V. (2002)
      Biochemistry 41, 13989-14000). Here we characterized this conformation using pure
      mouse MDR3 P-glycoprotein and natural MgATP and MgADP. Mutants E552A/E1197A,
      E552Q/E1197Q, E552D/E1197D, and E552K/E1197K had low but real ATPase activity in
      the order Ala > Gln > Asp > Lys, emphasizing the requirement for Glu
      stereochemistry. Mutant E552A/E1197A bound MgATP and MgADP (1 mol/mol) with K(d)
      9.2 and 92 microm, showed strong temperature sensitivity of MgATP binding and
      equal dissociation rates for MgATP and MgADP. With MgATP as the added ligand, 80%
      of bound nucleotide was in the form of ATP. None of these parameters was vanadate
      sensitive. The other mutants showed lower stoichiometry of MgATP and MgADP
      binding, in the order Ala > Gln > Asp > Lys. We conclude that the E552A/E1197A
      mutation arrests the enzyme in a conformation, likely a stabilized NBD dimer,
      which occludes nucleotide, shows preferential binding of ATP, does not progress
      to a normal vanadate-sensitive transition state, but hydrolyzes ATP and releases
      ADP slowly. Impairment of turnover is primarily due to inability to form the
      normal transition state rather than to slow ADP release. The Gln, Asp, and Lys
      mutants are less effective at stabilizing the occluded nucleotide, putative
      dimeric NBD, conformation. We envisage that in wild-type the occluded nucleotide
      conformation occurs transiently after MgATP binds to both NBDs with associated
      dimerization, and before progression to the transition state.

PMID- 15159389
TI  - NMR structure of a type IVb pilin from Salmonella typhi and its assembly into
      pilus.
AB  - The structure of the N-terminal-truncated Type IVb structural pilin (t-PilS) from
      Salmonella typhi was determined by NMR. Although topologically similar to the
      recently determined x-ray structure of pilin from Vibrio cholerae toxin
      coregulated pilus, the only Type IVb pilin with known structure, t-PilS contains
      many distinct structural features. The protein contains an extra pair of beta
      strands in the N-terminal alphabeta loop that align with the major beta-strands
      to form a continuous 7-stranded antiparallel beta-sheet. The C-terminal disulfide
      bonded region of t-PilS is only half the length of that of toxin-coregulated
      pilus pilin. A model of S. typhi pilus has been proposed and mutagenesis studies
      suggested that residues on both the alphabeta loop and the C-terminal disulfide
      bonded region of PilS might be involved in binding specificity of the pilus. This
      model structure reveals an exposed surface between adjacent subunits of PilS that
      could be a potential binding site for the cystic fibrosis transmembrane
      conductance regulator.

PMID- 15159390
TI  - Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive
      contacts.
AB  - Classical cadherin adhesion molecules are fundamental determinants of cell-cell
      recognition that function in cooperation with the actin cytoskeleton. Productive
      cadherin-based cell recognition is characterized by a distinct morphological
      process of contact zone extension, where limited initial points of adhesion are
      progressively expanded into broad zones of contact. We recently demonstrated that
      E-cadherin ligation recruits the Arp2/3 actin nucleator complex to the plasma
      membrane in regions where cell contacts are undergoing protrusion and extension.
      This suggested that Arp2/3 might generate the protrusive forces necessary for
      cell surfaces to extend upon one another during contact assembly. We tested this
      hypothesis in mammalian cells by exogenously expressing the CA region of N-WASP.
      This fragment, which potently inhibits Arp2/3-mediated actin assembly in vitro,
      also effectively reduced actin assembly at cadherin adhesive contacts. Blocking
      Arp2/3 activity by this strategy profoundly reduced the ability of cells to
      extend cadherin adhesive contacts but did not affect cell adhesiveness. These
      findings demonstrate that Arp2/3 activity is necessary for cells to efficiently
      extend and assemble cadherin-based adhesive contacts.

PMID- 15159392
TI  - Extensive domain motion and electron transfer in the human electron transferring
      flavoprotein.medium chain Acyl-CoA dehydrogenase complex.
AB  - The crystal structure of the human electron transferring flavoprotein
      (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of
      protein-protein interaction, imparting both specificity and promiscuity in the
      interaction of ETF with a range of structurally distinct primary dehydrogenases.
      ETF partitions the functions of partner binding and electron transfer between (i)
      the recognition loop, which acts as a static anchor at the ETF.MCAD interface,
      and (ii) the highly mobile redox active FAD domain. Together, these enable the
      FAD domain of ETF to sample a range of conformations, some compatible with fast
      interprotein electron transfer. Disorders in amino acid or fatty acid catabolism
      can be attributed to mutations at the protein-protein interface. Crucially,
      complex formation triggers mobility of the FAD domain, an induced disorder that
      contrasts with general models of protein-protein interaction by induced fit
      mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the
      basis for the interaction of ETF with structurally diverse protein partners.
      Solution studies using ETF and MCAD with mutations at the protein-protein
      interface support this dynamic model and indicate ionic interactions between MCAD
      Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive
      conformations of the FAD domain leading to enhanced electron transfer rates
      between both partners.

PMID- 15159393
TI  - Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium.
AB  - Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes.
      Therefore, the concept of stimulating myocyte mitotic divisions has dramatic
      implications for cardiomyocyte regeneration and hence, cardiovascular disease.
      Previous reports describing manipulation of cell cycle proteins have not shown
      induction of cardiomyocyte mitosis after birth. We now report that cyclin A2,
      normally silenced in the postnatal heart, induces cardiac enlargement because of
      cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into
      adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an
      increase in cardiomyocyte mitosis, noted in transgenic hearts at all time points
      examined, particularly during postnatal development. Several stages of mitosis
      were observed within cardiomyocytes and correlated with the nuclear localization
      of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These
      results reveal a previously unrecognized critical role for cyclin A2 in mediating
      cardiomyocyte mitosis, a role that may significantly impact upon clinical
      treatment of damaged myocardium.

PMID- 15159391
TI  - Intron retention generates a novel Id3 isoform that inhibits vascular lesion
      formation.
AB  - The expression of intron-containing messages has been shown to occur in a variety
      of diseases including lactic acidosis, Cowden Syndrome, and several cancers.
      However, it is unknown whether these intron-containing messages result in protein
      production in vivo. Indeed, intron-containing RNAs are typically retained in the
      nucleus, targeted for degradation, or are repressed translationally. Here, we
      show that during vascular lesion formation in rats, an alternative isoform of the
      helix-loop-helix transcription factor Id3 (Id3a) generated by intron retention is
      abundantly expressed. We demonstrate that Id3 is expressed early in lesion
      formation when the proliferative index of the neointima is highest and that Id3
      promotes smooth muscle cell (SMC) proliferation and S-phase entry and inhibits
      transcription of the cell-cycle inhibitor p21(Cip1). Using an Id3a-specific
      antibody developed by our laboratory, we show that Id3a protein is induced during
      vascular lesion formation and that Id3a expression peaks late when the
      proliferative index is low or declining and extensive apoptosis is observed.
      Furthermore, Id3a fails to promote SMC growth and S-phase entry or to inhibit
      p21(Cip1) promoter transactivation. In contrast, Id3a stimulates SMC apoptosis
      and inhibits endogenous Id3 production. Adenoviral delivery of Id3a inhibited
      lesion formation in balloon-injured rat carotid arteries in vivo. These data
      describe a novel feedback loop whereby intron retention generates an Id3 isoform
      that acts to limit SMC growth during vascular lesion formation, providing the
      first evidence that regulated intron retention can modulate a pathologic process
      in vivo.

PMID- 15159394
TI  - Jak2 tyrosine kinase mediates oxidative stress-induced apoptosis in vascular
      smooth muscle cells.
AB  - In vascular smooth muscle cells, Jak2 tyrosine kinase becomes activated in
      response to oxidative stress in the form of hydrogen peroxide. Although it has
      been postulated that hydrogen peroxide-induced Jak2 activation promotes cell
      survival, this has never been tested. We therefore examined the role that Jak2
      plays in vascular smooth muscle cell apoptosis following hydrogen peroxide
      treatment. Here, we report that Jak2 tyrosine kinase activation by hydrogen
      peroxide is required for apoptosis of vascular smooth muscle cells. Upon
      treatment of primary rat aortic smooth muscle cells with hydrogen peroxide, we
      observed laddering of genomic DNA and nuclear condensation, both hallmarks of
      apoptotic cells. However, apoptosis was prevented by either the expression of a
      dominant negative Jak2 protein or by the Jak2 pharmacological inhibitor AG490.
      Moreover, expression of the proapoptotic Bax protein was induced following
      hydrogen peroxide treatment. Again, expression of a dominant negative Jak2
      protein or treatment of cells with AG490 prevented this Bax induction. Following
      Bax induction by hydrogen peroxide, mitochondrial membrane integrity was
      compromised, and caspase-9 became activated. In contrast, in cells expressing a
      Jak2 dominant negative we observed that mitochondrial membrane integrity was
      preserved, and no caspase-9 activation occurred. These data demonstrate that the
      activation of Jak2 tyrosine kinase by hydrogen peroxide is essential for
      apoptosis of vascular smooth muscle cells. Furthermore, this report identifies
      Jak2 as a potential therapeutic target in vascular diseases in which vascular
      smooth muscle cell apoptosis contributes to pathological progression.

PMID- 15159396
TI  - Plasticity of extended subsites facilitates divergent substrate recognition by
      Kex2 and furin.
AB  - Yeast Kex2 and human furin are subtilisin-related proprotein convertases that
      function in the late secretory pathway and exhibit similar though distinguishable
      patterns of substrate recognition. Although both enzymes prefer Arg at P(1) and
      basic residues at P(2), the two differ in recognition of P(4) and P(6) residues.
      To probe P(4) and P(6) recognition by Kex2p, furin-like substitutions were made
      in the putative S(4) and S(6) subsites of Kex2. T252D and Q283E mutations were
      introduced to increase the preference for Arg at P(4) and P(6), respectively.
      Glu(255) was replaced with Ile to limit recognition of P(4) Arg. The effects of
      putative S(4) and S(6) mutations were determined by examining the cleavage by
      purified mutant enzymes of a series of fluorogenic substrates with systematic
      changes in P(4) and/or P(6). Whereas wild Kex2 exhibited little preference type
      for Arg at P(6), the T252D mutant and T252D/Q283E double mutant exhibited clear
      interactions with P(6) Arg. Moreover, the T252D and T252D/Q283E substitutions
      altered the influence of the P(6) residue on P(4) recognition. We infer that
      cross-talk between S(4) and S(6), not seen in furin, allows wild type and mutant
      forms of Kex2 to adapt their subsites for altered modes of recognition. This
      apparent plasticity may allow the subsites to rearrange their local environment
      to interact with different substrates in a productive manner. E255I-Kex2
      exhibited significantly decreased recognition of P(4) Arg in a tetrapeptide
      substrate with Lys at P(1), although the general pattern of selectivity for
      aliphatic residues at P(4) remained unchanged.

PMID- 15159395
TI  - Expression of the alpha7 isoform of hepatocyte nuclear factor (HNF) 4 is
      activated by HNF6/OC-2 and HNF1 and repressed by HNF4alpha1 in the liver.
AB  - The hepatocyte nuclear factor (HNF) 4alpha gene possesses two promoters, proximal
      P1 and distal P2, whose use results in HNF4alpha1 and HNF4alpha7 transcripts,
      respectively. Both isoforms are expressed in the embryonic liver, whereas
      HNF4alpha1 is almost exclusively in the adult liver. A 516-bp fragment,
      encompassing a DNase I-hypersensitive site associated with P2 activity that is
      still retained in adult liver, contains functional HNF1 and HNF6 binding sites
      and confers full promoter activity in transient transfections. We demonstrate a
      critical role of the Onecut factors in P2 regulation using site-directed
      mutagenesis and embryos doubly deficient for HNF6 and OC-2 that show reduced
      hepatic HNF4alpha7 transcript levels. Transient transgenesis showed that a 4-kb
      promoter region is sufficient to drive expression of a reporter gene in the
      stomach, intestine, and pancreas, but not the liver, for which additional
      activating sequences may be required. Quantitative PCR analysis revealed that
      throughout liver development HNF4alpha7 transcripts are lower than those of
      HNF4alpha1. HNF4alpha1 represses P2 activity in transfection assays and as
      deduced from an increase in P2-derived transcript levels in recombinant mice in
      which HNF4alpha1 has been deleted and replaced by HNF4alpha7. We conclude that
      although HNF6/OC-2 and perhaps HNF1 activate the P2 promoter in the embryo,
      increasing HNF4alpha1 expression throughout development causes a switch to
      essentially exclusive P1 promoter activity in the adult liver.

PMID- 15159397
TI  - BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S
      arrest following ionizing radiation-induced DNA damage.
AB  - BRCA1 is a major player in the DNA damage response. This is evident from its
      loss, which causes cells to become sensitive to a wide variety of DNA damaging
      agents. The major BRCA1 binding partner, BARD1, is also implicated in the DNA
      damage response, and recent reports indicate that BRCA1 and BARD1 co-operate in
      this pathway. In this report, we utilized small interfering RNA to deplete BRCA1
      and BARD1 to demonstrate that the BRCA1-BARD1 complex is required for ATM/ATR
      (ataxia-telangiectasia-mutated/ATM and Rad3-related)-mediated phosphorylation of
      p53(Ser-15) following IR- and UV radiation-induced DNA damage. In contrast,
      phosphorylation of a number of other ATM/ATR targets including H2AX, Chk2, Chk1,
      and c-jun does not depend on the presence of BRCA1-BARD1 complexes. Moreover,
      prior ATM/ATR-dependent phosphorylation of BRCA1 at Ser-1423 or Ser-1524
      regulates the ability of ATM/ATR to phosphorylate p53(Ser-15) efficiently.
      Phosphorylation of p53(Ser-15) is necessary for an IR-induced G(1)/S arrest via
      transcriptional induction of the cyclin-dependent kinase inhibitor p21.
      Consistent with these data, repressing p53(Ser-15) phosphorylation by BRCA1-BARD1
      depletion compromises p21 induction and the G(1)/S checkpoint arrest in response
      to IR but not UV radia-tion. These findings suggest that BRCA1-BARD1 complexes
      act as an adaptor to mediate ATM/ATR-directed phosphorylation of p53, influencing
      G(1)/S cell cycle progression after DNA damage.

PMID- 15159399
TI  - Comparative biochemical analysis suggests that vinculin and metavinculin
      cooperate in muscular adhesion sites.
AB  - Metavinculin, the muscle-specific splice variant of the cell adhesion protein
      vinculin, is characterized by a 68-amino acid insert within the C-terminal tail
      domain. The findings that mutations within this region correlate with hereditary
      idiopathic dilated cardiomyopathy in man suggest a specific contribution of
      metavinculin to the molecular architecture of muscular actin-membrane attachment
      sites, the nature of which, however, is still unknown. In mice, metavinculin is
      expressed in smooth and skeletal muscle, where it co-localizes with vinculin in
      dense plaques and costameres, respectively, but is of conspicuously low abundance
      in the heart. Immunoprecipitates suggest that both isoforms are present in the
      same complex. On the molecular level, both vinculin isoforms are regulated via an
      intramolecular head-tail interaction, with the metavinculin tail domain having a
      lower affinity for the head as compared with the vinculin tail. In addition,
      metavinculin displays impaired binding to acidic phospholipids and reduced
      homodimerization. Only in the presence of phospholipid-activated vinculin tail,
      the metavinculin tail domain is readily incorporated into heterodimers.
      Mutational analysis revealed that the metavinculin insert significantly alters
      binding of the C-terminal hairpin loop to acidic phospholipids. In summary, our
      data lead to a model in which unfurling of the metavinculin tail domain is
      impaired by the negative charges of the 68-amino acid insert, thus requiring
      vinculin to fully activate the metavinculin molecule. As a consequence,
      microfilament anchorage may be modulated at muscular adhesion sites through
      heterodimer formation.

PMID- 15159398
TI  - The galactolipid digalactosyldiacylglycerol accumulates in the peribacteroid
      membrane of nitrogen-fixing nodules of soybean and Lotus.
AB  - The peribacteroid membrane (PBM) surrounding nitrogen fixing rhizobia in the
      nodules of legumes is crucial for the exchange of ammonium and nutrients between
      the bacteria and the host cell. Digalactosyldiacylglycerol (DGDG), a galactolipid
      abundant in chloroplasts, was detected in the PBM of soybean (Glycine max) and
      Lotus japonicus. Analyses of membrane marker proteins and of fatty acid
      composition confirmed that DGDG represents an authentic PBM lipid of plant origin
      and is not derived from the bacteria or from plastid contamination. In
      Arabidopsis, DGDG is known to accumulate in extraplastidic membranes during
      phosphate deprivation. However, the presence of DGDG in soybean PBM was not
      restricted to phosphate limiting conditions. Complementary DNA sequences
      corresponding to the two DGDG synthases, DGD1 and DGD2 from Arabidopsis, were
      isolated from soybean and Lotus. The two genes were expressed during later stages
      of nodule development in infected cells and in cortical tissue. Because nodule
      development depends on the presence of high amounts of phosphate in the growth
      medium, the accumulation of the non-phosphorus galactolipid DGDG in the PBM might
      be important to save phosphate for other essential processes, i.e. nucleic acid
      synthesis in bacteroids and host cells.

PMID- 15159400
TI  - The DNase-I binding loop of actin may play a role in the regulation of actin
      myosin interaction by tropomyosin/troponin.
AB  - Various lines of evidence suggest that communication between tropomyosin and
      myosin in the regulation of vertebrate-striated muscle contraction involves yet
      unknown changes in actin conformation. Possible participation of loop 38-52 in
      this communication has recently been questioned based on unimpaired Ca(2+)
      regulation of myosin interaction, in the presence of the tropomyosin-troponin
      complex, with actin cleaved by subtilisin between Met(47) and Gly(48). We have
      compared the effects of actin cleavage by subtilisin and by protease ECP32,
      between Gly(42) and Val(43), on its interaction with myosin S1 in the presence
      and absence of tropomyosin or tropomyosin-troponin. Both individual modifications
      reduced activation of S1 ATPase by actin to a similar extent. The effect of ECP
      cleavage, but not of subtilisin cleavage, was partially reversed by stabilization
      of interprotomer contacts with phalloidin, indicating different pathways of
      signal transmission from the N- and C-terminal parts of loop 38-52 to myosin
      binding sites. ECP cleavage diminished the affinity to tropomyosin and reduced
      its inhibition of acto-S1 ATPase at low S1 concentrations, but increased the
      tropomyosin-mediated cooperative enhancement of the ATPase by S1 binding to
      actin. These effects were reversed by phalloidin. Subtilisin-cleaved actin more
      closely resembled unmodified actin than the ECP-modified actin. Limited
      proteolysis of the modified and unmodified F-actins revealed an allosteric effect
      of ECP cleavage on the conformation of the actin subdomain 4 region that is
      presumably involved in tropomyosin binding. Our results point to a possible role
      of the N-terminal part of loop 38-52 of actin in communication between
      tropomyosin and myosin through changes in actin structure.

PMID- 15159401
TI  - Biochemical and functional characterization of protein kinase CK2 in ascidian
      Ciona intestinalis oocytes at fertilization. Cloning and sequence analysis of
      cDNA for alpha and beta subunits.
AB  - The ubiquitous and pleiotropic dual specificity protein kinase CK2 has been
      studied and characterized in many organisms, from yeast to mammals. Generally,
      the enzyme is composed of two catalytic (alpha and/or alpha') and two regulatory
      (beta) subunits, forming a differently assembled tetramer. Although prone to
      controversial interpretation, the function of CK2 has been associated with
      fundamental biological processes such as signal transduction, cell cycle
      progression, cell growth, apoptosis, and transcription. Less known is the role of
      CK2 during meiosis and the early phase of embryogenesis. In this work, we studied
      CK2 activity during oocyte activation, a process occurring at the end of oocyte
      maturation and triggered by fertilization. In ascidian Ciona intestinalis, an
      organism whose complete genome has been published recently, CK2 was
      constitutively active in unfertilized and fertilized oocytes. The enzymatic
      activity oscillated through meiosis showing three major peaks: soon after
      fertilization (metaphase I exit), before metaphase II, and at the exit from
      metaphase II. Biochemical analysis of CK2 subunit composition in activated
      oocytes indicated that CK2-alpha was catalytically active as a monomer,
      independently from its regulatory subunit beta; however, CK2-beta was only
      detectable in unfertilized oocytes where it was associated with a bona fide
      identified ascidian mitogen-activated protein kinase. After fertilization, CK2
      beta was undetectable, suggesting its rapid degradation. Protein sequence
      analysis of CK2-alpha and -beta cDNA indicated a high identity compared with
      vertebrate homologs. In addition, the absence of putative phosphorylation sites
      for Cdc2 kinase on both alpha and beta subunits suggested an important role for
      CK2 in regulating meiotic cell cycle in C. intestinalis oocytes.

PMID- 15159402
TI  - Identification of interaction partners and substrates of the cyclin A1-CDK2
      complex.
AB  - The CDK2-associated cyclin A1 is essential for spermatogenesis and contributes to
      leukemogenesis. The detailed molecular functions of cyclin A1 remain unclear,
      since the molecular networks involving cyclin A1-CDK2 have not been elucidated.
      Here, we identified novel cyclin A1/CDK2 interaction partners in a yeast triple
      hybrid approach. Several novel proteins (INCA1, KARCA1, and PROCA1) as well as
      the known proteins GPS2 (G-protein pathway suppressor 2), Ku70, receptor for
      activated protein kinase C1/guanine nucleotide-binding protein beta-2-like-1, and
      mRNA-binding motif protein 4 were identified as interaction partners. These
      proteins link the cyclin A1-CDK2 complex to diverse cellular processes such as
      DNA repair, signaling, and splicing. Interactions were confirmed by GST pull-down
      assays and co-immunoprecipitation. We cloned and characterized the most
      frequently isolated unknown gene, which we named INCA1 (inhibitor of CDK
      interacting with cyclin A1). The nuclear INCA1 protein is evolutionarily
      conserved and lacks homology to any known gene. This novel protein and two other
      interacting partners served as substrates for the cyclin A1-CDK2 kinase complex.
      Cyclin A1 and all interaction partners were highly expressed in testis with
      varying degrees of tissue specificity. The highest expression levels were
      observed at different time points during testis maturation, whereas expression
      levels in germ cell cancers and infertile testes decreased. Taken together, we
      identified testicular interaction partners of the cyclin A1-CDK2 complex and
      studied their expression pattern in normal organs, testis development, and
      testicular malignancies. Thereby, we establish a new basis for future functional
      analyses of cyclin A1. We provide evidence that the cyclin A1-CDK2 complex plays
      a role in several signaling pathways important for cell cycle control and
      meiosis.

PMID- 15159403
TI  - Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C
      mediated calcium signal.
AB  - Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine
      receptors, several lines of evidence indicate that they are functionally linked.
      However, a mechanism for this linkage has not been elucidated. In this study, we
      demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted
      in an increase of intracellular calcium levels via a signaling pathway not
      activated by either receptor alone or when only one of the co-expressed receptors
      was activated by a selective agonist. Calcium signaling by D1-D2 receptor co
      activation was abolished following treatment with a phospholipase C inhibitor but
      not with pertussis toxin or inhibitors of protein kinase A or protein kinase C,
      indicating coupling to the G(q) pathway. We also show, by co-immunoprecipitation
      from rat brain and from cells co-expressing the receptors, that D1 and D2
      receptors are part of the same heteromeric protein complex and, by
      immunohistochemistry, that these receptors are co-expressed and co-localized
      within neurons of human and rat brain. This demonstration that D1 and D2
      receptors have a novel cellular function when co-activated in the same cell
      represents a significant step toward elucidating the mechanism of the functional
      link observed between these two receptors in brain.

PMID- 15159404
TI  - Oligomerization of the sensory and motor neuron-derived factor prevents protein O
      glycosylation.
AB  - The sensory and motor neuron-derived factor (SMDF) is a neuregulin that promotes
      Schwann cell proliferation and differentiation. Hence, understanding axon
      myelination is important to unveil the mechanisms involved in SMDF biogenesis,
      membrane delivery, and compartmentalization. SMDF is a type II membrane protein
      expressed as two distinct polypeptides of approximately 40 and 83 kDa. Whether
      the 83-kDa polypeptide results from posttranslational modifications of the
      protein monomers or protein dimerization remains unknown. Here we have addressed
      this question and shown that the 83-kDa polypeptide is an O-glycosylated form of
      the protein. Deletion of the N-terminal domain fully abrogates the SMDF O
      glycosylation, indicating that incorporation of O-glycans occurs in the
      intracellular domain of the protein. Notably, O-glycosylated forms are excluded
      from partitioning into lipid raft microdomains. In addition, we found that
      heterologously expressed SMDF monomers interact in intact living cells as
      evidenced from fluorescence resonance energy transfer of cyan fluorescent
      protein/yellow fluorescent protein.SMDF fusion proteins. A stepwise deletion
      approach demonstrated that SMDF self-association is primarily determined by its
      transmembrane segment. Notably, biochemical analysis revealed that SMDF multimers
      are exclusively composed of the 40-kDa polypeptide. Collectively, these findings
      indicate that the 40-kDa form corresponds to unmodified SMDF, which may be
      present as multimers, whereas the 83-kDa polypeptide is a monomeric O
      glycosylated form of the protein. Furthermore, our observations imply a role for
      oligomerization as a potential modulator of the distribution in membrane domains
      and O-glycosylation of the protein.

PMID- 15159405
TI  - The interaction between HIV-1 Gag and APOBEC3G.
AB  - APOBEC3G, a member of an RNA/DNA cytidine deaminase superfamily, has been
      identified as a cellular inhibitor of HIV-1 infectivity, possibly through the dC
      to dU deamination of the first minus strand cDNA synthesized during reverse
      transcription. Virions incorporate APOBEC3G during viral assembly in non
      permissive cells, and this incorporation is inhibited by the viral protein Vif.
      The mechanism of APOBEC3G incorporation into HIV-1 is examined in this report. In
      the absence of Vif, cytoplasmic APOBEC3G becomes membrane-bound in cells
      expressing HIV-1 Gag, and its incorporation into Gag viral-like particles (VLPs)
      is proportional to the amount of APOBEC3G expressed in the cell. The expression
      of Vif, or mutant Gag unable to bind to membrane, prevents the APOBEC3G
      association with membrane. HIV-1 Gag alone among viral proteins is sufficient for
      packaging of APOBEC3G into Gag VLPs, and this incorporation requires the presence
      of Gag nucleocapsid. The presence of amino acids 104-156 in APOBEC3G, located in
      the linker region between two zinc coordination motifs, is also required for its
      incorporation into Gag VLPs. Evidence against an RNA bridge facilitating the
      Gag/APOBEC3G interaction includes data indicating that 1) the incorporation of
      APOBEC3G occurs independently of viral genomic RNA, 2) a Gag/APOBEC3G complex is
      immunoprecipitated from cell lysate after RNase treatment, and 3) the zinc
      coordination motif, rather than the regions flanking this motif, have been
      implicated in RNA binding in another family member, APOBEC1.

PMID- 15159406
TI  - Directed evolution of human estrogen receptor variants with significantly
      enhanced androgen specificity and affinity.
AB  - Human estrogen receptor alpha (hERalpha) and human androgen receptor exhibit
      exquisite ligand specificity, which underlies their remarkable ability to effect
      ligand-regulated gene transcription in a highly distinctive and specific manner.
      Here we used a directed evolution approach to create hERalpha variants with
      enhanced androgen specificity and affinity with the goal to better understand the
      molecular basis of ER ligand specificity and the evolutionary mechanism of
      nuclear receptors. We developed a sensitive yeast two-hybrid system to screen for
      hERalpha variants with increased transactivation potency toward testosterone.
      After two rounds of directed evolution, we identified five hERalpha variants with
      dramatically improved transactivation potency toward testosterone in both yeast
      and mammalian cells. These variants showed up to 7,600-fold improvement in the
      binding affinity for testosterone and only slightly reduced affinity toward
      17beta-estradiol. Detailed analysis of these evolved variants and a few site
      directed mutants generated de novo led to several unexpected findings including
      the following. 1) Only two beneficial mutations were needed to create hERalpha
      variants with near nanomolar affinity for testosterone. 2) Some beneficial
      mutations were synergistic, context-dependent, or non-additive. 3) Of the five
      identified beneficial mutations, four of them were not in the ER ligand binding
      pocket and yet exerted important action on ligand specificity. 4) The single
      ligand-contacting mutation E353Q plays a dominant role in discriminating
      androgens and estrogens. These results, viewed in conjunction with the ligand
      exploitation model of nuclear receptor evolution, suggest that the mutation E353Q
      may represent a key event in the evolution of androgen receptors from an
      ancestral estrogen receptor and that ligand promiscuity may play an important
      role in the creation of new nuclear receptors via divergent evolution.

PMID- 15159407
TI  - MEKK1 signaling through p38 leads to transcriptional inactivation of E47 and
      repression of skeletal myogenesis.
AB  - Activation of the Raf kinase signal transduction pathway in skeletal myoblasts
      causes a complete cessation of myofiber formation and muscle gene expression. The
      negative impacts of the signaling pathway are realized through downstream
      activation of mitogen and extracellular kinase (MEK) phosphorylation-dependent
      events and MEK-independent signal transmission. MEKK1, a kinase that can
      physically associate with Raf, may contribute to the MEK-independent signaling in
      response to elevated Raf activity. Myogenic cells overexpressing activated Raf
      and kinase-defective MEKK1 remain differentiation-defective, suggesting that
      MEKK1 does not contribute to the inhibitory actions of Raf. However, constitutive
      activation of MEKK1 dramatically inhibits biochemical and morphological measures
      of muscle formation. MEKK1 inhibits MyoD-directed transcriptional activity
      without altering the ability of the protein to form heterodimers with E2A
      proteins or bind DNA. By contrast, the transcriptional activity of E47, the
      preferred dimer partner of the myogenic regulatory factors, is severely
      compromised by MEKK1-initiated signaling. Inhibition of MEK1/2 and JNK1/2
      function did not reinstate E47-directed transcription, indicating that these two
      downstream kinases likely are not involved in the MEKK1-controlled
      transcriptional block. Inhibition of p38 signaling overcame the negative effects
      exerted by MEKK1 on the amino terminus of E47. Closer examination indicates that
      E47 is phosphorylated in vitro by p38, and deletion analysis predicts that the
      critical amino acid(s) phosphorylated by p38 lie outside of the minimal
      transcriptional activation domains. Thus, modification of E47 by p38 likely
      disrupts higher order protein complex formation that is necessary for muscle gene
      transcription.

PMID- 15159408
TI  - Mitogen-activated protein kinase phosphatase-3 is a tumor promoter target in
      initiated cells that express oncogenic Ras.
AB  - We have capitalized on the unique properties of the skin tumor promoter
      palytoxin, which does not activate protein kinase C, to investigate alternative
      mechanisms by which major signaling molecules can be modulated during
      carcinogenesis. We report here that palytoxin activates extracellular signal
      regulated kinase (ERK) through a novel mechanism that involves inactivation of an
      ERK phosphatase in keratinocytes derived from initiated mouse skin (308 cells).
      Use of U0126 revealed that palytoxin requires the ERK kinase MEK to stimulate ERK
      activity, although palytoxin did not activate MEK. We found that 308
      keratinocytes highly express mitogen-activated protein kinase phosphatase-3 (MKP
      3), which selectively inactivates ERK. Palytoxin induced the loss of MKP-3 in a
      manner that corresponded to increased ERK phosphorylation. Complementary studies
      showed that sustained expression of exogenous MKP-3 inhibited palytoxin
      stimulated ERK activation. As is characteristic of initiated keratinocytes, 308
      cells express activated H-Ras. To investigate whether expression of oncogenic Ras
      is key to palytoxin-stimulated ERK activation, we determined how palytoxin
      affected ERK and MKP-3 in MCF10A human breast epithelial cells and in H-ras
      MCF10A cells, which stably express activated H-Ras. Palytoxin did not affect ERK
      activity in MCF10A cells, which had no detectable MKP-3. Like 308 cells, H-ras
      MCF10A cells highly express MKP-3. Strikingly, palytoxin stimulated ERK activity
      and induced a corresponding loss of MKP-3 in H-ras MCF10A cells. These studies
      indicate that in initiated cells palytoxin unleashes ERK activity by down
      regulating MKP-3, an ERK inhibitor, and further suggest that MKP-3 may be a
      vulnerable target in cells that express oncogenic Ras.

PMID- 15159409
TI  - A caspase-8-independent signaling pathway activated by Fas ligation leads to
      exposure of the Bak N terminus.
AB  - Bak is a pro-apoptotic member of the Bcl-2 family that is activated by apoptotic
      stimulation: its activation is characterized by conformational changes such as
      exposure of the N terminus and oligomerization. In death receptor-mediated
      apoptosis, the activation of Bak depends on activation of caspase-8. However, we
      found that exposure of the N terminus of Bak (but not oligomerization) can occur
      in the absence of active caspase-8. Although exposure of the N terminus of Bak
      without oligomerization is not sufficient to release cytochrome c from the
      mitochondria and commit cells to apoptosis, this change sensitizes the
      mitochondria to apoptotic signals (including Bid) and thus sensitizes cells to
      apoptotic death. Fas-induced, caspase-8-independent exposure of the N terminus of
      Bak is blocked by staurosporine, a pan protein kinase inhibitor. These results
      suggest that Fas stimulation not only activates caspase-8, but also a distinct
      signaling pathway involving protein kinase(s) to induce exposure of the N
      terminus of Bak.

PMID- 15159411
TI  - Probing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site
      directed mutagenesis.
AB  - The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella)
      gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in
      penicillins, cephalosporins, and carbapenems. FEZ-1 has been extensively studied
      using kinetic, computational modeling and x-ray crystallography. In an effort to
      probe residues potentially involved in substrate binding and zinc binding, five
      site-directed mutants of FEZ-1 (H121A, Y156A, S221A, N225A, and Y228A) were
      prepared and characterized using metal analyses and steady state kinetics. The
      activity of H121A is dependent on zinc ion concentration. The H121A monozinc form
      is less active than the dizinc form, which exhibits an activity similar to that
      of the wild type enzyme. Tyr156 is not essential for binding and hydrolysis of
      the substrate. Substitution of residues Ser221 and Asn225 modifies the substrate
      profile by selectively decreasing the activity against carbapenems. The Y228A
      mutant is inhibited by the product formed upon hydrolysis of cephalosporins. A
      covalent bond between the side chain of Cys200 and the hydrolyzed cephalosporins
      leads to the formation of an inactive and stable complex.

PMID- 15159412
TI  - Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit
      endocytosis of receptor tyrosine kinases.
AB  - The ubiquitin (Ub) ligase Cbl plays a critical role in attenuation of receptor
      tyrosine kinase (RTK) signaling by inducing ubiquitination of RTKs and promoting
      their sorting for endosomal degradation. Herein, we describe the identification
      of two novel Cbl-interacting proteins, p70 and Clip4 (recently assigned the names
      Sts-1 and Sts-2, respectively), that inhibit endocytosis of epidermal growth
      factor receptor (EGFR) and platelet-derived growth factor receptor. Sts-1 and Sts
      2 contain SH3 domains that interacted with Cbl, Ub-associated domains, which
      bound directly to mono-Ub or to the EGFR/Ub chimera as well as phosphoglycerate
      mutase domains that mediated oligomerization of Sts-1/2. Ligand-induced
      recruitment of Sts-1/Sts-2 into activated EGFR complexes led to inhibition of
      receptor internalization, reduction in the number of EGFR-containing endocytic
      vesicles, and subsequent block of receptor degradation followed by prolonged
      activation of mitogenic signaling pathways. On the other hand, interference with
      Sts-1/Sts-2 functions diminished ligand-induced receptor degradation, cell
      proliferation, and oncogenic transformation in cultured fibroblasts. We suggest
      that Sts-1 and Sts-2 represent a novel class of Ub-binding proteins that regulate
      RTK endocytosis and control growth factor-induced cellular functions.

PMID- 15159410
TI  - Activation of AMP-activated protein kinase inhibits protein synthesis associated
      with hypertrophy in the cardiac myocyte.
AB  - A necessary mediator of cardiac myocyte enlargement is protein synthesis, which
      is controlled at the levels of both translation initiation and elongation.
      Eukaryotic elongation factor-2 (eEF2) mediates the translocation step of peptide
      chain elongation and is inhibited through phosphorylation by eEF2 kinase. In
      addition, p70S6 kinase can regulate protein synthesis by phosphorylating eEF2
      kinase or via phosphorylation of ribosomal protein S6. We have recently shown
      that eEF2 kinase is also controlled by phosphorylation by AMP-activated protein
      kinase (AMPK), a key regulator of cellular energy homeostasis. Moreover, the
      mammalian target of rapamycin has also been shown to be inhibited, indirectly, by
      AMPK, thus leading to the inhibition of p70S6 kinase. Although AMPK activation
      has been shown to modulate protein synthesis, it is unknown whether AMPK could
      also be a regulator of cardiac hypertrophic growth. Therefore, we investigated
      the role of AMPK activation in regulating protein synthesis during both
      phenylephrine- and Akt-induced cardiac hypertrophy. Metformin and 5
      aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside were used to activate AMPK
      in neonatal rat cardiac myocytes. Activation of AMPK significantly decreased
      protein synthesis induced by phenylephrine treatment or by expression of
      constitutively active Akt. Activation of AMPK also resulted in decreased p70S6
      kinase phosphorylation and increased phosphorylation of eEF2, suggesting that
      inhibition of protein synthesis involves the eEF2 kinase/eEF2 axis and/or the
      p70S6 kinase pathway. Together, our data suggest that the inhibition of protein
      synthesis by pharmacological activation of AMPK may be a key regulatory mechanism
      by which hypertrophic growth can be controlled.

PMID- 15159413
TI  - The position of a key tyrosine in dTDP-4-Keto-6-deoxy-D-glucose-5-epimerase
      (EvaD) alters the substrate profile for this RmlC-like enzyme.
AB  - Vancomycin, the last line of defense antibiotic, depends upon the attachment of
      the carbohydrate vancosamine to an aglycone skeleton for antibacterial activity.
      Vancomycin is a naturally occurring secondary metabolite that can be produced by
      bacterial fermentation. To combat emerging resistance, it has been proposed to
      genetically engineer bacteria to produce analogues of vancomycin. This requires a
      detailed understanding of the biochemical steps in the synthesis of vancomycin.
      Here we report the 1.4 A structure and biochemical characterization of EvaD, an
      RmlC-like protein that is required for the C-5' epimerization during synthesis of
      dTDP-epivancosamine. EvaD, although clearly belonging to the RmlC class of
      enzymes, displays very low activity in the archetypal RmlC reaction (double
      epimerization of dTDP-6-deoxy-4-keto-D-glucose at C-3' and C-5'). The high
      resolution structure of EvaD compared with the structures of authentic RmlC
      enzymes indicates that a subtle change in the enzyme active site repositions a
      key catalytic Tyr residue. A mutant designed to re-establish the normal position
      of the Tyr increases the RmlC-like activity of EvaD.

PMID- 15159414
TI  - Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and
      without rituximab as front-line treatment for patients with follicular lymphoma.
AB  - PURPOSE: Promising new therapeutic options for follicular lymphoma (FL) include
      fludarabine plus mitoxantrone (FM) and the mouse/human anti-CD20 antibody,
      rituximab. We performed a randomized comparative trial of FM with
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) front-line
      chemotherapy with and without sequential rituximab. PATIENTS AND METHODS: All
      previously untreated CD20(+) FL patients presenting in 15 Italian cooperative
      institutions from October 1999 were randomly allocated to FM or CHOP. Following
      clinical or molecular restaging, patients in complete remission (CR) with bcl
      2/IgH negativity (CR(-)) received no further treatment; those in CR with bcl
      2/IgH positivity (CR(+)) received rituximab, as did those in partial remission
      (PR) with bcl-2/IgH negativity (PR(-)) or positivity (PR(+)); nonresponders (NR
      subgroup) were off study. RESULTS: After chemotherapy, the FM arm achieved higher
      rates of CR (68% [49 of 72 patients] v 42% [29 of 68 patients]; P =.003) and CR(
      ) (39% [28 of 72 patients] v 13 of 68 patients [19%]; P =.001). Rituximab
      elicited CR(-) in 55 of 95 treated patients (58%). The final CR(-) rate was
      higher in the FM arm (71% [51 of 72 patients] v 51% [35 of 68 patients]; P =.01).
      However, with a median follow-up of 19 months (range, 9 to 37 months), no
      statistically significant difference was found among the various study arms in
      terms of both progression-free (PFS) and overall survival (OS). CONCLUSION: These
      results indicate that FM is superior to CHOP for front-line treatment of FL and
      that rituximab is an effective sequential treatment option. However, they also
      confirm that this superiority is unlikely to translate into either better PFS or
      OS.

PMID- 15159415
TI  - 53BP1 is required for class switch recombination.
AB  - 53BP1 participates early in the DNA damage response and is involved in cell cycle
      checkpoint control. Moreover, the phenotype of mice and cells deficient in 53BP1
      suggests a defect in DNA repair (Ward et al., 2003b). Therefore, we asked whether
      or not 53BP1 would be required for the efficient repair of DNA double strand
      breaks. Our data indicate that homologous recombination by gene conversion does
      not depend on 53BP1. Moreover, 53BP1-deficient mice support normal V(D)J
      recombination, indicating that 53BP1 is not required for "classic" nonhomologous
      end joining. However, class switch recombination is severely impaired in the
      absence of 53BP1, suggesting that 53BP1 facilitates DNA end joining in a way that
      is not required or redundant for the efficient closing of RAG-induced strand
      breaks. These findings are similar to those observed in mice or cells deficient
      in the tumor suppressors ATM and H2AX, further suggesting that the functions of
      ATM, H2AX, and 53BP1 are closely linked.

PMID- 15159416
TI  - A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and
      cofilin in lamellipodia.
AB  - Cofilin mediates lamellipodium extension and polarized cell migration by
      stimulating actin filament dynamics at the leading edge of migrating cells.
      Cofilin is inactivated by phosphorylation at Ser-3 and reactivated by cofilin
      phosphatase Slingshot-1L (SSH1L). Little is known of signaling mechanisms of
      cofilin activation and how this activation is spatially regulated. Here, we show
      that cofilin-phosphatase activity of SSH1L increases approximately 10-fold by
      association with actin filaments, which indicates that actin assembly at the
      leading edge per se triggers local activation of SSH1L and thereby stimulates
      cofilin-mediated actin turnover in lamellipodia. We also provide evidence that 14
      3-3 proteins inhibit SSH1L activity, dependent on the phosphorylation of Ser-937
      and Ser-978 of SSH1L. Stimulation of cells with neuregulin-1beta induced Ser-978
      dephosphorylation, translocation of SSH1L onto F-actin-rich lamellipodia, and
      cofilin dephosphorylation. These findings suggest that SSH1L is locally activated
      by translocation to and association with F-actin in lamellipodia in response to
      neuregulin-1beta and 14-3-3 proteins negatively regulate SSH1L activity by
      sequestering it in the cytoplasm.

PMID- 15159417
TI  - Loss of Geminin induces rereplication in the presence of functional p53.
AB  - Strict regulation of DNA replication is essential to ensure proper duplication
      and segregation of chromosomes during the cell cycle, as its deregulation can
      lead to genomic instability and cancer. Thus, eukaryotic organisms have evolved
      multiple mechanisms to restrict DNA replication to once per cell cycle. Here, we
      show that inactivation of Geminin, an inhibitor of origin licensing, leads to
      rereplication in human normal and tumor cells within the same cell cycle. We
      found a CHK1-dependent checkpoint to be activated in rereplicating cells
      accompanied by formation of gammaH2AX and RAD51 nuclear foci. Abrogation of the
      checkpoint leads to abortive mitosis and death of rereplicated cells. In
      addition, we demonstrate that the induction of rereplication is dependent on the
      replication initiation factors CDT1 and CDC6, and independent of the functional
      status of p53. These data show that Geminin is required for maintaining genomic
      stability in human cells.

PMID- 15159418
TI  - MuSK is required for anchoring acetylcholinesterase at the neuromuscular
      junction.
AB  - At the neuromuscular junction, acetylcholinesterase (AChE) is mainly present as
      asymmetric forms in which tetramers of catalytic subunits are associated to a
      specific collagen, collagen Q (ColQ). The accumulation of the enzyme in the
      synaptic basal lamina strictly relies on ColQ. This has been shown to be mediated
      by interaction between ColQ and perlecan, which itself binds dystroglycan. Here,
      using transfected mutants of ColQ in a ColQ-deficient muscle cell line or COS-7
      cells, we report that ColQ clusterizes through a more complex mechanism. This
      process requires two heparin-binding sites contained in the collagen domain as
      well as the COOH terminus of ColQ. Cross-linking and immunoprecipitation
      experiments in Torpedo postsynaptic membranes together with transfection
      experiments with muscle-specific kinase (MuSK) constructs in MuSK-deficient
      myotubes or COS-7 cells provide the first evidence that ColQ binds MuSK.
      Together, our data suggest that a ternary complex containing ColQ, perlecan, and
      MuSK is required for AChE clustering and support the notion that MuSK dictates
      AChE synaptic localization at the neuromuscular junction.

PMID- 15159419
TI  - Affixin interacts with alpha-actinin and mediates integrin signaling for
      reorganization of F-actin induced by initial cell-substrate interaction.
AB  - The linking of integrin to cytoskeleton is a critical event for an effective cell
      migration. Previously, we have reported that a novel integrin-linked kinase (ILK)
      binding protein, affixin, is closely involved in the linkage between integrin and
      cytoskeleton in combination with ILK. In the present work, we demonstrated that
      the second calponin homology domain of affixin directly interacts with alpha
      actinin in an ILK kinase activity-dependent manner, suggesting that integrin-ILK
      signaling evoked by substrate adhesion induces affixin-alpha-actinin interaction.
      The overexpression of a peptide corresponding to the alpha-actinin-binding site
      of affixin as well as the knockdown of endogenous affixin by small interference
      RNA resulted in the blockade of cell spreading. Time-lapse observation revealed
      that in both experiments cells were round with small peripheral blebs and failed
      to develop lamellipodia, suggesting that the ILK-affixin complex serves as an
      integrin-anchoring site for alpha-actinin and thereby mediates integrin signaling
      to alpha-actinin, which has been shown to play a critical role in actin
      polymerization at focal adhesions.

PMID- 15159420
TI  - Coalignment of plasma membrane channels and protrusions (fibripositors) specifies
      the parallelism of tendon.
AB  - The functional properties of tendon require an extracellular matrix (ECM) rich in
      elongated collagen fibrils in parallel register. We sought to understand how
      embryonic fibroblasts elaborate this exquisite arrangement of fibrils. We show
      that procollagen processing and collagen fibrillogenesis are initiated in Golgi
      to plasma membrane carriers (GPCs). These carriers and their cargo of 28-nm-diam
      fibrils are targeted to previously unidentified plasma membrane (PM) protrusions
      (here designated "fibripositors") that are parallel to the tendon axis and
      project into parallel channels between cells. The base of the fibripositor lumen
      (buried several microns within the cell) is a nucleation site of collagen
      fibrillogenesis. The tip of the fibripositor is the site of fibril deposition to
      the ECM. Fibripositors are absent at postnatal stages when fibrils increase in
      diameter by accretion of extracellular collagen, thereby maintaining parallelism
      of the tendon. Thus, we show that the parallelism of tendon is determined by the
      late secretory pathway and interaction of adjacent PMs to form extracellular
      channels.

PMID- 15159423
TI  - Thoughts and memories from Bob Boutilier's students and postdoctoral fellows.

PMID- 15159424
TI  - Social responses without early experience: Australian brush-turkey chicks use
      specific visual cues to aggregate with conspecifics.
AB  - Almost all birds depend upon early experience with adults and siblings to learn
      recognition cues. Megapodes, such as the Australian brush-turkey (Alectura
      lathami), have evolved a very different life history. Eggs are incubated in
      mounds of decaying organic material. Chicks hatch asynchronously and receive no
      parental care, so imprinting cannot occur. Nevertheless, chicks subsequently form
      groups with similar-aged conspecifics. We explored the perceptual basis of this
      aggregation response, focussing on likely visual cues, such as pecking movements
      and body colour. Experiments were conducted under naturalistic conditions in a
      large aviary, using realistic robot models and colour filters. The robots
      successfully evoked a range of social responses resembling those of a live
      companion. Aggregation depended upon both behaviour and morphology. Simultaneous
      choice tests revealed that brush-turkey chicks preferred a pecking robot over
      either a static model or a scanning robot, suggesting that responsiveness depends
      upon particular movement patterns. In addition, chicks were sensitive to changes
      in appearance but only those that affected radiance at short wavelengths. The
      mechanism underlying social aggregation after hatching hence involves relatively
      specific cues. This perceptual bias seems to be largely experience independent
      and may exploit attributes to which potential predators are insensitive.

PMID- 15159421
TI  - NG2-expressing cells in the subventricular zone are type C-like cells and
      contribute to interneuron generation in the postnatal hippocampus.
AB  - The subventricular zone (SVZ) is a source of neural progenitors throughout brain
      development. The identification and purification of these progenitors and the
      analysis of their lineage potential are fundamental issues for future brain
      repair therapies. We demonstrate that early postnatal NG2-expressing (NG2+)
      progenitor cells located in the SVZ self-renew in vitro and display phenotypic
      features of transit-amplifier type C-like multipotent cells. NG2+ cells in the
      SVZ are highly proliferative and express the epidermal growth factor receptor,
      the transcription factors Dlx, Mash1, and Olig2, and the Lewis X (LeX) antigen.
      We show that grafted early postnatal NG2+ cells generate hippocampal GABAergic
      interneurons that propagate action potentials and receive functional
      glutamatergic synaptic inputs. Our work identifies Dlx+/Mash1+/LeX+/NG2+/GFAP
      negative cells of the SVZ as a new class of postnatal multipotent progenitor
      cells that may represent a specific cellular reservoir for renewal of postnatal
      and adult inhibitory interneurons in the hippocampus.

PMID- 15159425
TI  - Environmental influence on testicular MAP kinase (ERK1) activity in the frog Rana
      esculenta.
AB  - Recent studies suggest a role for ERK1 in the regulation of spermatogonial
      proliferation. In this report the frog Rana esculenta, a seasonal breeder, was
      used as a model to study the possible effect on ERK1 of photoperiod and
      temperature. Adult male R. esculenta were subjected to several combinations of
      light and temperature at different times of the year to elucidate the regulation
      of ERK1 testicular activity in the spermatogonial proliferation by these
      environmental factors. Western blot analysis shows that under controlled
      experimental conditions an increase of temperature and photoperiod in November,
      characterized by a decrease in primary spermatogonial mitosis, induces ERK1
      activity and spermatogonial proliferation, as confirmed using the proliferating
      cellular nuclear antigen (PCNA) as an early molecular marker. In contrast, a
      decrease in temperature and photoperiod in March, with an increase of primary
      spermatogonial mitosis, impairs ERK1 activity and spermatogonial proliferation.
      In conclusion, our data clearly show for the first time in a non-mammalian
      vertebrate that the temperature and the photoperiod exert a role in the
      spermatogonial proliferation via ERK1 activity.

PMID- 15159426
TI  - Negative effects of early developmental stress on yolk testosterone levels in a
      passerine bird.
AB  - Female birds incorporate in the yolks of their eggs significant concentrations of
      a number of different androgens. Yolk androgen has been shown to positively
      affect several fitness components at the embryo, nestling and juvenile stages.
      Previous experiments have shown that females lay eggs with higher androgen
      concentrations when they are paired with highly ornamented males. This pattern
      suggests that yolk androgens are costly to females. In this study, we
      experimentally manipulated adult female condition in zebra finches Taeniopygia
      guttata by modifying the level of developmental stress they suffered as
      nestlings. This was achieved by cross-fostering nestlings to broods of varying
      brood size. Subsequently, we measured the yolk testosterone contents of the
      female offspring that resulted from the experimental manipulation. As predicted,
      females deposited decreasing concentrations of testosterone with increasing brood
      sizes experienced as nestlings: testosterone concentration (mean +/- S.E.M.) of
      eggs laid by females from small broods, 20.66+/-2.08 pg mg(-1); medium broods,
      15.32+/-1.94 pg mg(-1); and large broods, 14.51+/-1.66 pg mg(-1). Additionally,
      testosterone concentration decreased with laying order, and varied with clutch
      size in a complex way. Differences in egg testosterone between females exposed to
      different brood sizes are in line with previous findings in showing that early
      developmental stress can affect adult reproductive performance, although our
      study did not detect an effect in other breeding parameters, such as latency to
      breed or clutch size. Furthermore, the results are consistent with the hypothesis
      that there is a cost associated with yolk testosterone. However, it is still
      unclear what the nature of this cost may be, and whether it is paid by females,
      offspring, or both.

PMID- 15159427
TI  - Relationship between the energetic cost of burrowing and genetic variability
      among populations of the pocket gopher, T. bottae: does physiological fitness
      correlate with genetic variability?
AB  - Many studies have reported relationships between genetic variability and fitness
      characters in invertebrates, but there is a paucity of such studies in mammals.
      Here, we use a statistically powerful paired sampling design to test whether the
      metabolic cost of burrowing, an important physiological trait in the pocket
      gopher, Thomomys bottae, correlates with genetic variability. Three pairs of
      pocket gopher populations were used, with each pair selected from a different
      subspecies and comprising one high genetic variability and one low genetic
      variability population. Genetic variability was measured using average allozyme
      heterozygosity and two measures of DNA fingerprint band sharing. In addition, the
      cost of burrowing for individuals from each population was determined from the
      oxygen consumption per gram of body mass per unit of work performed. Our results
      indicate that the cost of burrowing was significantly higher in populations with
      lower genetic variability (3-way ANCOVA, P=0.0150); mass-adjusted cost of
      burrowing in the low variability populations averaged 0.57+/-0.24 ml O2 g(-1)
      kgm(-1) and that in the high variability populations averaged 0.42+/-0.19 ml O2
      g(-1) kgm(-1). The magnitude of the population differences in cost of burrowing
      was associated with the magnitude of difference in genetic variability. We
      conclude that population differences in genetic variability are reflected in
      physiological fitness differences for a trait that is essential to gopher
      survival.

PMID- 15159428
TI  - The stability of telomereless chromosome fragments in adult androgenetic rainbow
      trout.
AB  - The study provides new data on the stability of gamma radiation-induced
      chromosome fragments of a putative maternal nuclear genome in an androgenetic
      vertebrate, rainbow trout (Oncorhynchus mykiss Walbaum). The fragments were found
      in five of 16 examined individuals and they were mostly centromeric parts of
      metacentric or subtelocentric chromosomes. Chromosome fragments were identical in
      all cells of a given androgenetic individual, indicating that segregation of
      chromosome fragments is active from the early cell divisions. Most of the
      fragments were telomereless, i.e. they had no telomeric sequences on their ends.
      This shows that telomeres are not necessary for stability of chromosomal
      structures in a vertebrate genome. In one individual, the interstitial telomeric
      sites were found in chromosomes, which could be the effect of joining chromosome
      fragments.

PMID- 15159429
TI  - Changes in gene expression associated with acclimation to constant temperatures
      and fluctuating daily temperatures in an annual killifish Austrofundulus
      limnaeus.
AB  - Eurythermal ectotherms commonly thrive in environments that expose them to large
      variations in temperature on daily and seasonal bases. The roles played by
      alterations in gene expression in enabling eurytherms to adjust to these two
      temporally distinct patterns of thermal stress are poorly understood. We used
      cDNA microarray analysis to examine changes in gene expression in a eurythermal
      fish, Austrofundulus limnaeus, subjected to long-term acclimation to constant
      temperatures of 20, 26 and 37 degrees C and to environmentally realistic daily
      fluctuations in temperature between 20 degrees C and 37 degrees C. Our data
      reveal major differences between the transcriptional responses in the liver made
      during acclimation to constant temperatures and in response to daily temperature
      fluctuations. Control of cell growth and proliferation appears to be an important
      part of the response to change in temperature, based on large-scale changes in
      mRNA transcript levels for several key regulators of these pathways. However,
      cell growth and proliferation appear to be regulated by different genes in
      constant versus fluctuating temperature regimes. The gene expression response of
      molecular chaperones is also different between constant and fluctuating
      temperatures. Small heat shock proteins appear to play an important role in
      response to fluctuating temperatures whereas larger molecular mass chaperones
      such as Hsp70 and Hsp90 respond more strongly to chronic high temperatures. A
      number of transcripts that encode for enzymes involved in the biosynthesis of
      nitrogen-containing organic osmolytes have gene expression patterns that indicate
      a possible role for these 'chemical chaperones' during acclimation to chronic
      high temperatures and daily temperature cycling. Genes important for the
      maintenance of membrane integrity are highly responsive to temperature change.
      Changes in fatty acid saturation may be important in long-term acclimation and in
      response to fluctuating temperatures; however cholesterol metabolism may be most
      critical for short-term acclimation to fluctuating temperatures. The variable
      effect of temperature on the expression of genes with daily rhythms of expression
      indicates that there is a complex interaction between the temperature cycle and
      daily rhythmicity in gene expression. A number of new hypotheses concerning
      temperature acclimation in fish have been generated as a result of this study.
      The most notable of these hypotheses is the possibility that the high mobility
      group b1 (HMGB1) protein, which plays key roles in the assembly of transcription
      initiation and enhanceosome complexes, may act as a compensatory modulator of
      transcription in response to temperature, and thus as a global gene expression
      temperature sensor. This study illustrates the utility of cDNA microarray
      approaches in both hypothesis-driven and 'discovery-based' investigations of
      environmental effects on organisms.

PMID- 15159430
TI  - Dietary influences over proliferating cell nuclear antigen expression in the
      locust midgut.
AB  - We have studied the influence of variations in dietary protein (P) and digestible
      carbohydrate (C), the quantity of food eaten, and insect age during the fifth
      instar on the expression of the proliferating cell nuclear antigen (PCNA) in the
      epithelial cells of the midgut (with special reference to the midgut caeca) in
      the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA
      immunostained cells was used as an indirect measure of the levels of expression
      of PCNA, and a PCNA cellular index (PCNA-I) was obtained. Measurements of the DNA
      content of the cells have also been carried out by means of microdensitometry of
      Feulgen-stained, thick sections of midgut. A comparison between the PCNA nuclear
      level and the DNA content was performed. The PCNA levels were significantly
      different among the cells of the five regions studied: caeca, anterior ventricle,
      medial ventricle, posterior ventricle and ampullae of the Malpighian tubules. We
      have studied in more detail the region with highest PCNA-I, i.e. the caeca. The
      quality and the quantity of food eaten under ad libitum conditions were highly
      correlated with both the PCNA and DNA levels in the caeca cells. Locusts fed a
      diet with a close to optimal P:C content (P 21%, C 21%) showed the highest PCNA
      and DNA content. In locusts fed a food that also contained a 1:1 ratio of P to C
      but was diluted three-fold by addition of indigestible cellulose (P 7%, C 7%), a
      compensatory increase in consumption was critical to maintaining PCNA levels. Our
      measurements also showed that the nuclear DNA content of the mature and
      differentiated epithelial cells was several-fold higher than the levels in the
      undifferentiated stem cells of the regenerative nests. These results, combined
      with the low number of mitotic figures found in the regenerative nests of the
      caeca and the marked variation in PCNA levels among groups, suggest that some
      type of DNA endoreduplication process may be taking place. Our data also indicate
      that the DNA synthetic activity in the midgut is related to feeding in locusts.
      The possible dietary and nutritional regulatory mechanisms and the significance
      of the differences found are discussed.

PMID- 15159431
TI  - Temperature-dependent oxygen limitation in insect eggs.
AB  - Most terrestrial insect embryos support metabolism with oxygen from the
      environment by diffusion across the eggshell. Because metabolism is more
      temperature sensitive than diffusion, embryos should be relatively oxygen-limited
      at high temperatures. We tested whether survival, development time and metabolism
      of eggs of a moth, Manduca sexta, were sensitive to experimentally imposed
      variation in atmospheric oxygen availability (5-50 kPa; normoxia at sea level is
      21 kPa) across a range of biologically realistic temperatures. Temperature-oxygen
      interactions were apparent in most experiments. Hypoxia affected survival more
      strongly at warmer temperatures. Metabolic rates, measured as rates of CO2
      emission, were virtually insensitive to hypo- and hyperoxia at 22 degrees C but
      were strongly influenced at 37 degrees C. Radial profiles of P(O2) inside eggs,
      measured using an oxygen microelectrode, demonstrated that 3-day-old eggs had
      broad central volumes with P(O2) less than 2 kPa, and that higher temperature led
      to lower P(O2). These data indicate that at realistically high temperatures (32
      37 degrees C) eggs of M. sexta were oxygen limited, even in normoxia. This result
      has important implications for insect population ecology and the evolution of
      eggshell structures, and it suggests a novel hypothesis about insect gigantism
      during Paleozoic hyperoxia.

PMID- 15159432
TI  - Mechanical function of two ankle extensors in wild turkeys: shifts from energy
      production to energy absorption during incline versus decline running.
AB  - We investigated the mechanical function of two ankle extensor muscles, the
      lateral gastrocnemius (LG) and peroneus longus (PL), in wild turkeys Meleagris
      gallopavo during steady speed running. We hypothesized that mechanical work
      output of the LG and PL during running parallels the demand for mechanical work
      on the body. The turkeys ran on level, inclined (+6 degrees, +12 degrees ) and
      declined (-6 degrees, -12 degrees ) treadmills to change the demand for
      mechanical work. Simultaneous measurements of muscle length (from sonomicrometry)
      and muscle force (from tendon strain gauges) were used to calculate mechanical
      work output. During level running at a speed of 2 m s(-1), the LG and PL were
      both active in stance but produced peak force at different times, at
      approximately 21% of stance duration for the LG and 70% for the PL. The LG and PL
      also had different length patterns in stance during level running. The LG
      underwent little shortening during force production, resulting in negligible net
      positive work (2.0+/-0.8 J kg(-1)). By contrast, the PL produced force across a
      stretch-shorten cycle in stance and did significant net positive work (4.7+/-1.6
      J kg(-1)). Work outputs for both the LG and PL were directly proportional to
      running slope. When we increased the demand for net positive work by running the
      turkeys on an incline, the LG and PL increased stance net positive work output in
      direct proportion to slope (P<0.05). Stance net positive work output increased to
      7.0+/-1.3 J kg(-1) for the LG and 8.1+/-2.9 J kg(-1) for the PL on the steepest
      incline. Increases in stance net positive work for the LG and PL were associated
      with increases in net shortening strain and average shortening velocity, but
      average force in stance remained constant. The LG and PL muscles were also
      effective energy absorbers during decline running, when there is demand for net
      negative work on the body. During decline running at 2 m s(-1) on the steepest
      slope, the LG absorbed 4.6+/-2.2 J kg(-1) of net work in stance and the PL
      absorbed 2.4+/-0.9 J kg(-1) of net work. Shifts in muscle mechanical function
      from energy production during incline running to energy absorption during decline
      running were observed over a range of running speeds from 1-3 m s(-1) for both
      the LG and PL. Two fundamentally different mechanisms for changing work output
      were apparent in the mechanical behavior of the LG and PL. The LG simply altered
      its length pattern; it actively shortened during incline running to produce
      mechanical energy and actively lengthened during decline running to absorb
      mechanical energy. The PL changed mechanical function by altering its length
      pattern and by shifting the timing of force production across its stretch-shorten
      cycle. During incline running, the PL produced force during late stance
      shortening for positive work, but during decline running, the timing of force
      production shifted into early stance, to align with lengthening for negative
      work. In addition, during decline running, the PL greatly reduced or eliminated
      late stance shortening, thus reducing the potential for positive work. Our
      results show that the changing demands for whole body work during steady speed
      running are met, at least in part, by an ability of single muscles to shift
      mechanical function from net energy production to net energy absorption.

PMID- 15159433
TI  - Differences in the effects of salinity on larval growth and developmental
      programs of a freshwater and a euryhaline mosquito species (Insecta: Diptera,
      Culicidae).
AB  - The effects of salinity on growth and development of the euryhaline Ochlerotatus
      taeniorhynchus and the freshwater Aedes aegypti are compared. O. taeniorhynchus
      grow larger, and have greater intrinsic growth rates, than A. aegypti. Females of
      each species attain greater mass, take longer to develop, and have greater growth
      rates than do males. In O. taeniorhynchus, pupal mass, larval stage duration and
      growth rates (dry mass) increase with salinity, whereas growth rates (wet mass)
      remain constant across salinities, reflecting a decrease in percent body water.
      The pupal mass (wet or dry) of O. taeniorhynchus is determined primarily by
      effects of salinity on the rate of assimilation of dry mass, because the latter
      contributes very strongly to final pupal mass in both species. In contrast, the
      duration of A. aegypti larval stage follows a upsilon-shaped curve, with most
      rapid development at intermediate salinities. Growth rates of A. aegypti decrease
      with increasing salinity, and percent body water is constant across salinities.
      As for O. taeniorhynchus, duration of A. aegypti larval stage increases at high
      salinity. However, this increase in larval stage duration cannot compensate for
      the decrease in growth rate at high salinity, resulting in an overall decrease in
      both wet and dry pupal mass at high salinity. Thus, salinity has fundamentally
      different effects on developmental programs and phenotypic plasticity in the two
      species investigated.

PMID- 15159434
TI  - pH tolerances and regulatory abilities of freshwater and euryhaline Aedine
      mosquito larvae.
AB  - The pH regulatory abilities of two members of the mosquito tribe Aedini, known to
      have dramatically different saline tolerances, are investigated. The freshwater
      mosquito Aedes aegypti and the euryhaline Ochlerotatus taeniorhynchus tolerate
      very similar pH ranges. Both species complete larval development in waters
      ranging from pH 4 to pH 11, but naive larvae always die in water of pH 3 or 12.
      Across the pH range 4-11, the hemolymph pH of O. taeniorhynchus is maintained
      constant while that of A. aegypti varies by 0.1 pH units. The salt composition of
      the water (3.5 g l(-1) sea salt, 3.5 g l(-1) NaCl, or nominally salt-free) has no
      effect on the range of pH tolerated by A. aegypti. In both species, the effects
      of pH on larval growth and development are minor in comparison with the influence
      of species and sex. Acclimation of A. aegypti to pH 4 or 11 increases survival
      times in pH 3 or 12, respectively, and allows a small percentage of larvae to
      pupate successfully at these extreme pH values. Such acclimation does not
      compromise survival at the other pH extreme.

PMID- 15159435
TI  - Respiration rate of hepatocytes varies with body mass in birds.
AB  - Hepatocytes were isolated from eight species of birds ranging from 13 g zebra
      finches to 35 kg emus. This represents a 2800-fold range of body mass (Mb). Liver
      mass (g) was allometrically related to species body mass by the equation: liver
      mass=19.6 x Mb(0.91). There was a significant allometric decline in hepatocyte
      respiration rate (HRR; nmol O2 mg(-1) dry mass min(-1)) with species body mass
      (kg) described by the relationship: HRR=5.27 x Mb(-0.10). The proportions of
      hepatocyte oxygen consumption devoted to (i) mitochondrial ATP production, (ii)
      mitochondrial proton leak and (iii) non-mitochondrial processes were estimated by
      using excess amounts of appropriate inhibitors. It was found that although
      hepatocyte respiration rate varied with body mass in birds, these processes
      constitute a relatively constant proportion of hepatocyte metabolic rate
      irrespective of the size of the bird species. The respective percentages were
      54%, 21% and 25%. The portion of hepatocyte respiration devoted to ATP production
      for use by the sodium pump was estimated and found to be a relatively constant
      24% of hepatocyte respiration and 45% of mitochondrial ATP production in
      different-sized bird species. These results are discussed in the context of
      competing theories to explain the metabolism-body size allometry, and are found
      to support the 'allometric cascade' model.

PMID- 15159436
TI  - Osmotic regulation in adult Drosophila melanogaster during dehydration and
      rehydration.
AB  - We have examined the osmoregulatory capacities of laboratory populations of the
      insect Drosophila melanogaster by measuring hemolymph osmotic concentration
      during desiccation and upon recovery from a bout of desiccation. Recovery
      treatments entailed allowing the flies access to distilled water, a saline
      solution or a saline+sucrose solution after a desiccation bout shown to reduce
      hemolymph volume by approximately 60%. Prior to desiccation, the hemolymph
      osmotic concentration was 353+/-11 mOsm. We found that Drosophila display strict
      osmotic regulation under prolonged conditions of dehydration. Osmotic regulation
      continued during recovery from desiccation, regardless of the fluid provided.
      This result is evidence that this insect does not require an external source of
      osmolytes or energy to regulate its hemolymph osmotic concentration or to restore
      hemolymph volume, which is reduced during desiccation. We also examined
      populations that have been selected for over 250 generations for enhanced
      desiccation resistance to identify physiological characters that have evolved in
      response to the selection regime. The selected lines displayed a reduced pre
      desiccation hemolymph osmotic concentration (315+/-7 mOsm) and a marginally
      improved capacity for osmoregulation.

PMID- 15159437
TI  - Preliminary characterization of two atypical soluble guanylyl cyclases in the
      central and peripheral nervous system of Drosophila melanogaster.
AB  - Conventional soluble guanylyl cyclases form alpha/beta heterodimers that are
      activated by nitric oxide (NO). Recently, atypical members of the soluble
      guanylyl cyclase family have been described that include the rat beta2 subunit
      and MsGC-beta3 from Manduca sexta. Predictions from the Drosophila melanogaster
      genome identify three atypical guanylyl cyclase subunits: Gyc-88E (formerly
      CG4154), Gyc-89Da (formerly CG14885) and Gyc-89Db (formerly CG14886). Preliminary
      data showed that transient expression of Gyc-88E in heterologous cells generated
      enzyme activity in the absence of additional subunits that was slightly
      stimulated by the NO donor sodium nitroprusside (SNP) but not the NO donor DEA
      NONOate or the NO-independent activator YC-1. Gyc-89Db was inactive when
      expressed alone but when co-expressed with Gyc-88E enhanced the basal and SNP
      stimulated activity of Gyc-88E, suggesting that they may form heterodimers in
      vivo. Here, we describe the localization of Gyc-88E and Gyc-89Db and show that
      they are expressed in the embryonic and larval central nervous systems and are
      colocalized in several peripheral neurons that innervate trachea, basiconical
      sensilla and the sensory cones in the posterior segments of the embryo. We also
      show that there are two splice variants of Gyc-88E that differ by seven amino
      acids, although no differences in biochemical properties could be determined. We
      have also extended our analysis of the NO activation of Gyc-88E and Gyc-89Db,
      showing that several structurally unrelated NO donors activate Gyc-88E when
      expressed alone or when co-expressed with Gyc-89Db.

PMID- 15159438
TI  - Escape manoeuvres in the spiny dogfish (Squalus acanthias).
AB  - The locomotor performance of dogfish during escape responses was observed by
      means of high-speed video. Dogfish show C-type escape responses that are
      comparable with those shown previously in teleosts. Dogfish show high variability
      of turning rates of the anterior part of the body (head to centre of mass), i.e.
      with peak values from 434 to 1023 deg. s(-1). We suggest that this variability
      may be due to the presence of two types of escape manoeuvres, i.e. responses with
      high and low turning rates, as previously found in a teleost species. Fast
      responses (i.e. with high maximum turning rates, ranging between 766 and 1023
      deg. s(-1)) showed significantly higher locomotor performance than slow responses
      (i.e. with low maximum turning rates, ranging between 434 and 593 deg. s(-1)) in
      terms of distance covered, speed and acceleration, although no differences were
      found in the turning radius of the centre of mass during the escape manoeuvres.
      The existence of two types of escape responses would have implications in terms
      of both neural control and muscular activation patterns. When compared with
      literature data for the locomotor performance of bony fishes, dogfish showed
      relatively low speed and acceleration, comparable turning rates and a turning
      radius that is in the low part of the range when compared with teleosts,
      indicating relatively high manoeuvrability. The locomotor performance observed in
      dogfish is consistent with their morphological characteristics: (1) low locomotor
      performance associated with low thrust developed by their relatively small
      posterior depth of section and (2) relatively high manoeuvrability associated
      with their high flexibility.

PMID- 15159439
TI  - Morphological plasticity varies with duration of infection: evidence from
      lactating and virgin wild-derived house mice (Mus musculus) infected with an
      intestinal parasite (Heligmosomoides polygyrus; Nematoda).
AB  - With chronic parasite infection, host response to the parasite may change
      throughout the duration of the infection as the host progresses from the acute to
      the chronic phase. We investigated the effects of parasite infection ranging in
      duration from 30 to 120 days on host morphology both alone and in combination
      with lactation by using captive wild-derived house mice (Mus musculus)
      experimentally infected with a naturally occurring intestinal nematode
      (Heligmosomoides polygyrus). We found that some changes in host morphology were
      greatest at 30-60 days post-infection (e.g. spleen mass) followed by a decline
      towards the control state whereas other morphological changes were greatest at 90
      120 days post-infection (e.g. small intestine mass) after a relatively steady
      increase with infection duration. For all infection durations, the morphological
      responses to parasite infection were similar for virgin and lactating mice
      (except for lean body mass). After accounting for changes in body mass with
      lactation, lactating mice increased organs of the gastrointestinal tract as well
      as liver and kidney but had less body fat than virgin mice. This is the first
      study to demonstrate that morphological plasticity of mice parasitized by H.
      polygyrus varies with infection duration and that this variation is generally
      similar for lactating and virgin mice.

PMID- 15159440
TI  - Upper thermal tolerance and oxygen limitation in terrestrial arthropods.
AB  - The hypothesis of oxygen limitation of thermal tolerance proposes that critical
      temperatures are set by a transition to anaerobic metabolism, and that upper and
      lower tolerances are therefore coupled. Moreover, this hypothesis has been dubbed
      a unifying general principle and extended from marine to terrestrial ectotherms.
      By contrast, in insects the upper and lower limits are decoupled, suggesting that
      the oxygen limitation hypothesis might not be as general as proposed. However, no
      direct tests of this hypothesis or its predictions have been undertaken in
      terrestrial species. We use a terrestrial isopod (Armadillidium vulgare) and a
      tenebrionid beetle (Gonocephalum simplex) to test the prediction that thermal
      tolerance should vary with oxygen partial pressure. Whilst in the isopod critical
      thermal maximum declined with declining oxygen concentration, this was not the
      case in the beetle. Efficient oxygen delivery via a tracheal system makes oxygen
      limitation of thermal tolerance, at a whole organism level, unlikely in insects.
      By contrast, oxygen limitation of thermal tolerances is expected to apply to
      species, like the isopod, in which the circulatory system contributes
      significantly to oxygen delivery. Because insects dominate terrestrial systems,
      oxygen limitation of thermal tolerance cannot be considered pervasive in this
      habitat, although it is a characteristic of marine species.

PMID- 15159441
TI  - 2'-deoxyribonolactone lesion produces G->A transitions in Escherichia coli.
AB  - 2'-deoxyribonolactone (dL) is a C1'-oxidized abasic site damage generated by a
      radical attack on DNA. Numerous genotoxic agents have been shown to produce dL
      including UV and gamma-irradiation, ene-dye antibiotics etc. At present the
      biological consequences of dL present in DNA have been poorly documented, mainly
      due to the lack of method for introducing the lesion in oligonucleotides. We have
      recently designed a synthesis of dL which allowed investigation of the
      mutagenicity of dL in Escherichia coli by using a genetic reversion assay. The
      lesion was site-specifically incorporated in a double-stranded bacteriophage
      vector M13G*1, which detects single-base-pair substitutions at position 141 of
      the lacZalpha gene by a change in plaque color. In E.coli JM105 the dL-induced
      reversion frequency was 4.7 x 10(-5), similar to that of the classic abasic site
      2'-deoxyribose (dR). Here we report that a dL residue in a duplex DNA codes
      mainly for thymidine. The processing of dL in vivo was investigated by measuring
      lesion-induced mutation frequencies in DNA repair deficient E.coli strains. We
      showed a 32-fold increase in dL-induced reversion rate in AP endonuclease
      deficient (xth nfo) mutant compared with wild-type strain, indicating that the
      Xth and Nfo AP endonucleases participate in dL repair in vivo.

PMID- 15159442
TI  - The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N
      dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in
      experimental allergic encephalomyelitis are associated with immunomodulation.
AB  - Poly(ADP-ribose) polymerase (PARP) activity has been implicated in the
      pathogenesis of several central nervous system (CNS) disorders. For example, the
      presence of extensive poly(ADP)ribosylation in CNS tissues from animals with
      experimental allergic encephalomyelitis (EAE) indicates that PARP activity may be
      involved in this inflammatory disease process. Using PJ34 [N-(6-oxo-5,6
      dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl], a selective PARP
      inhibitor, we studied the mechanisms through which PARP activity may contribute
      to the onset of acute EAE. PLSJL mice immunized with myelin antigens were treated
      with PJ34, and the effects on the progression of EAE and several other parameters
      relevant to the disease process were assessed. PJ34 exerted therapeutic effects
      at the onset of EAE that were associated with reduced CNS inflammation and the
      maintenance of neurovascular integrity. Expression of genes encoding the
      intercellular adhesion molecule-1 (ICAM-1) and the inflammatory mediators
      interferon-gamma, tumor necrosis factor-alpha, and inducible nitric-oxide
      synthase were decreased in CNS tissues from drug-treated animals. Administration
      of PJ34 biased the class of myelin basic protein (MBP)-specific antibodies
      elicited from IgG2a to IgG1 and IgG2b and modulated antigen-specific T-cell
      reactivity. Therefore, the mode of action of PJ34 at the onset of EAE is likely
      mediated by a shift in the MBP-specific immune response from a proinflammatory
      Th1 toward an anti-inflammatory Th2 phenotype.

PMID- 15159443
TI  - Comprehensive evaluation of tamoxifen sequential biotransformation by the human
      cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6.
AB  - We performed comprehensive kinetic, inhibition, and correlation analyses in human
      liver microsomes and experiments in expressed human cytochromes P450 (P450s) to
      identify primary and secondary metabolic routes of tamoxifen (TAM) and the P450s
      catalyzing these reactions at therapeutically relevant concentrations. N
      Desmethyl-TAM formation catalyzed by CYP3A4/5 was quantitatively the major
      primary metabolite of TAM; 4-hydroxy-TAM formation catalyzed by CYP2D6 (and other
      P450s) represents a minor route. Other minor primary metabolites include alpha -,
      3-, and 4'-hydroxyTAM and one unidentified metabolite (M-I) and were primarily
      catalyzed by CYP3A4, CYP3A5, CYP2B6/2C19, and CYP3A4, respectively. TAM secondary
      metabolism was examined using N-desmethyl- and 4-hydroxy-TAM as intermediate
      substrates. N-Desmethyl-TAM was predominantly biotransformed to alpha-hydroxy N
      desmethyl-, N-didesmethyl-, and 4-hydroxy N-desmethyl-TAM (endoxifen), whereas 4
      hydroxy-TAM was converted to 3,4-dihydroxyTAM and endoxifen. Except for the
      biotransformation of N-desmethyl-TAM to endoxifen, which was exclusively
      catalyzed by CYP2D6, all other routes of N-desmethyl- and 4-hydroxy-TAM
      biotransformation were catalyzed predominantly by the CYP3A subfamily. TAM and
      its primary metabolites undergo extensive oxidation, principally by CYP3A and
      CYP2D6 to metabolites that exhibit a range of pharmacological effects. Variable
      activity of these P450s, brought about by genetic polymorphisms and drug
      interactions, may alter the balance of TAM effects in vivo.

PMID- 15159445
TI  - Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of
      pitavastatin in humans.
AB  - Pitavastatin, a novel potent 3-hydroxymethylglutaryl-CoA reductase inhibitor, is
      selectively distributed to the liver in rats. However, the hepatic uptake
      mechanism of pitavastatin has not been clarified yet. In the present study, we
      investigated the contribution of organic anion transporting polypeptide 2
      (OATP2/OATP1B1) and OATP8 (OATP1B3) to pitavastatin uptake using transporter
      expressing HEK293 cells and human cryopreserved hepatocytes. Uptake studies using
      OATP2- and OATP8-expressing cells revealed a saturable and Na(+)-independent
      uptake, with K(m) values of 3.0 and 3.3 microM for OATP2 and OATP8, respectively.
      To determine which transporter is more important for its hepatic uptake, we
      proposed a methodology for estimating their quantitative contribution to the
      overall hepatic uptake by comparing the uptake clearance of pitavastatin with
      that of reference compounds (a selective substrate for OATP2 (estrone-3-sulfate)
      and OATP8 (cholecystokinin octapeptide) in expression systems and human
      hepatocytes. The concept of this method is similar to the so-called relative
      activity factor method often used in estimating the contribution of each
      cytochrome P450 isoform to the overall metabolism. Applying this method to
      pitavastatin, the observed uptake clearance in human hepatocytes could be almost
      completely accounted for by OATP2 and OATP8, and about 90% of the total hepatic
      clearance could be accounted for by OATP2. This result was also supported by
      estimating the relative expression level of each transporter in expression
      systems and hepatocytes by Western blot analysis. These results suggest that
      OATP2 is the most important transporter for the hepatic uptake of pitavastatin in
      humans.

PMID- 15159444
TI  - Domain swapping in the human histamine H1 receptor.
AB  - G-protein-coupled receptors (GPCRs) represent the largest family of receptors
      involved in transmembrane signaling. Although these receptors were generally
      believed to be monomeric entities, accumulating evidence supports the presence of
      GPCRs in multimeric forms. Here, using immunoprecipitation as well as time
      resolved fluorescence resonance energy transfer to assess protein-protein
      interactions in living cells, we unambiguously demonstrate the occurrence of
      dimerization of the human histamine H(1) receptor. We also show the presence of
      domain-swapped H(1) receptor dimers in which there is the reciprocal exchange of
      transmembrane domain TM domains 6 and 7 between the receptors present in the
      dimer. Mutation of aspartate(107) in transmembrane (TM) 3 or phenylalanine(432)
      in TM6 to alanine results in two radioligand-binding-deficient mutant H(1)
      receptors. Coexpression of H(1)D(107) A and H(1)F(432)A, however, results in a
      reconstituted radioligand binding site that exhibits a pharmacological profile
      that corresponds to the wild-type H(1) receptor. Interestingly, the H(1) receptor
      radioligands [(3)H]mepyramine and [(3)H]-(-)-trans-1-phenyl-3-N,N-dimethylamino
      1,2,3,4-tetrahydronaphthalene show differential saturation binding values
      (B(max)) for wild-type H(1) receptors but not for the radioligand binding site
      that is formed upon coexpression of H(1) D(107)A and H(1) F(432)A receptors,
      suggesting the presence of different H(1) receptor populations.

PMID- 15159446
TI  - Serofendic acid, a sulfur-containing diterpenoid derived from fetal calf serum,
      attenuates reactive oxygen species-induced oxidative stress in cultured striatal
      neurons.
AB  - We previously identified a novel endogenous substance, serofendic acid, from a
      lipophilic extract of fetal calf serum. Serofendic acid protects cultured
      cortical neurons against the cytotoxicity of glutamate and nitric oxide. Here, we
      reported the protective effect of serofendic acid on reactive oxygen species
      induced oxidative stress using primary rat striatal cultures. In addition, we
      compared the neuroprotective effect and the radical-scavenging activity of
      serofendic acid with those of dimethyl sulfoxide (DMSO), because serofendic acid
      possesses a DMSO structure. Paraquat caused neuronal death, which was inhibited
      by a cell-permeable superoxide dismutase (SOD) mimetic, Mn(III)tetrakis(4-benzoic
      acid)porphyrin chloride (Mn-TBAP); a cell-permeable SOD/catalase mimetic, EUK-134
      [manganese 3-methoxy N,N'-bis(salicylidene)ethylenediamine chloride]; and a
      ferrous ion chelator, 2,2'-dipyridyl, in rat striatal cultures. Serofendic acid
      (10-100 microM) suppressed the neurotoxicity of paraquat, whereas DMSO (10-100
      microM) did not. By contrast, higher concentrations (30-300 mM) of DMSO
      ameliorated the paraquat-induced cell death. Furthermore, H(2)O(2) induced
      neurotoxicity, which was prevented by EUK-134 and 2,2'-dipyridyl. Serofendic acid
      (10-100 microM) also protected striatal neurons against the H(2)O(2)-induced
      toxicity. Higher concentrations (30-300 mM) of DMSO ameliorated H(2)O(2)-induced
      neuronal death, whereas lower concentrations (10-100 microM) did not. Electron
      spin resonance spectrometry with a spin-trapping technique revealed that
      serofendic acid and DMSO had approximately the same ability to inhibit the
      formation of the hydroxyl radical (.OH). These results suggest that the.OH
      scavenging activity of serofendic acid is attributable to its DMSO structure and
      that the remaining components such as the atisane structure play an important
      role in eliciting neuroprotection at a concentration range of 10 to 100 microM.

PMID- 15159447
TI  - eNOS at a glance.

PMID- 15159448
TI  - Elizabeth Simpson. [interview by Fiona Watt].

PMID- 15159449
TI  - Barriers built on claudins.
AB  - The fundamental functions of epithelia and endothelia in multicellular organisms
      are to separate compositionally distinct compartments and regulate the exchange
      of small solutes and other substances between them. Tight junctions (TJs) between
      adjacent cells constitute the barrier to the passage of ions and molecules
      through the paracellular pathway and function as a 'fence' within the plasma
      membrane to create and maintain apical and basolateral membrane domains. How TJs
      achieve this is only beginning to be understood. Recently identified components
      of TJs include the claudins, a family of four-transmembrane-span proteins that
      are prime candidates for molecules that function in TJ permeability. Their
      identification and characterization have provided new insight into the diversity
      of different TJs and heterogeneity of barrier functions in different epithelia
      and endothelia.

PMID- 15159450
TI  - Mechanosensitive ion channels: molecules of mechanotransduction.
AB  - Cells respond to a wide variety of mechanical stimuli, ranging from thermal
      molecular agitation to potentially destructive cell swelling caused by osmotic
      pressure gradients. The cell membrane presents a major target of the external
      mechanical forces that act upon a cell, and mechanosensitive (MS) ion channels
      play a crucial role in the physiology of mechanotransduction. These detect and
      transduce external mechanical forces into electrical and/or chemical
      intracellular signals. Recent work has increased our understanding of their
      gating mechanism, physiological functions and evolutionary origins. In
      particular, there has been major progress in research on microbial MS channels.
      Moreover, cloning and sequencing of MS channels from several species has provided
      insights into their evolution, their physiological functions in prokaryotes and
      eukaryotes, and their potential roles in the pathology of disease.

PMID- 15159451
TI  - Distinct kinetic and mechanical properties govern selectin-leukocyte
      interactions.
AB  - Leukocytes are recruited from the bloodstream to sites of inflammation by the
      selectin family of adhesion receptors. In vivo and in vitro studies reveal
      distinctive rolling velocities of polymorphonuclear leukocytes over E-, P- and L
      selectin substrates. The kinetic and mechanical properties of the selectin-ligand
      bonds responsible for these differences at the single-molecule level are not well
      understood. Using single-molecule force spectroscopy, we probe in situ the
      rupture force, unstressed off-rate and reactive compliance of single selectin
      receptors to single ligands on whole human polymorphonuclear leukocytes (PMNs)
      under conditions that preserve the proper orientation and post-translational
      modifications of the selectin ligands. Single L-selectin bonds to PMNs were more
      labile than either E- or P-selectin in the presence of an applied force. This
      outcome, along with a higher unstressed off-rate and a higher reactive
      compliance, explain the faster L-selectin-mediated rolling. By quantifying
      binding frequency in the presence of a specific blocking monoclonal antibody or
      following enzyme treatment, we determined that P-selectin glycoprotein ligand-1
      is a high-affinity ligand for E-selectin on PMNs under force. The rupture force
      spectra and corresponding unstressed off-rate and reactive compliance of selectin
      ligand bonds provide mechanistic insights that might help to explain the variable
      rolling of leukocytes over different selectin substrates.

PMID- 15159452
TI  - Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear
      targeting of PLCzeta.
AB  - During the first cell cycle Ca2+ oscillations are regulated in a cell cycle
      dependent manner, such that the oscillations are unique to M phase. How the Ca2+
      oscillations are regulated with such cell cycle stage-dependency is unknown,
      despite their importance for egg activation and embryo development. We recently
      identified a novel, sperm-specific phospholipase C (PLCzeta; PLCzeta) that
      triggers Ca2+ oscillations similar to those caused by sperm. We show that PLCzeta
      induced Ca2+ oscillations also occur exclusively during M phase. The cell cycle
      dependency can be explained by PLCzeta's localisation to the pronuclei, which
      depends specifically upon a nuclear localisation signal sequence. Preventing
      pronuclear localisation of PLCzeta by mutation of the nuclear localisation
      signal, or by inhibiting pronuclear formation/import, can prolong Ca2+
      oscillations or allow them to occur during interphase. These data suggest a novel
      mechanism for regulating a PLC through nuclear sequestration and may explain the
      cell cycle-dependent regulation of Ca2+ oscillations following fertilisation.

PMID- 15159453
TI  - Matrix-mediated canal formation in primmorphs from the sponge Suberites domuncula
      involves the expression of a CD36 receptor-ligand system.
AB  - Sponges (Porifera), represent the phylogenetically oldest metazoan phylum still
      extant today. Recently, molecular biological studies provided compelling evidence
      that these animals share basic receptor/ligand systems, especially those involved
      in bodyplan formation and in immune recognition, with the higher metazoan phyla.
      An in vitro cell/organ-like culture system, the primmorphs, has been established
      that consists of proliferating and differentiating cells, but no canals of the
      aquiferous system. We show that after the transfer of primmorphs from the
      demosponge Suberites domuncula to a homologous matrix (galectin), canal-like
      structures are formed in these 3D-cell aggregates. In parallel with the formation
      of these structures a gene is expressed whose deduced protein falls into the
      CD36/LIMPII receptor family. The receptor was cloned and found to be strongly
      expressed after adhesion to the galectin matrix. This process was suppressed if
      primmorphs were co-incubated with a homologous polypeptide containing the CSVTCG
      domain, as found in thrombospondin-1 (and related) molecules of vertebrates. In
      situ hybridization studies revealed that the S. domuncula CD36/LIMPII receptor is
      localized in the pinacocytes that surround the canals of the sponge. Furthermore,
      a secondary metabolite from a sponge-associated bacterium was isolated and
      characterized, the 2-methylthio-1,4-naphthoquinone (MTN). MTN causes inhibition
      of cell proliferation of vertebrate tumor cells at concentrations of >80 ng/ml.
      However, doses of only 2 ng are required to potently inhibit angiogenesis in the
      chick chorio-allantoic membrane assay. At concentrations of 10 ng/ml this
      compound was also found to suppress the expression of the S. domuncula
      CD36/LIMPII; this result is a first indication that this secondary metabolite has
      a conserved functional activity: the suppression of the formation of the
      circulation system, from sponges to vertebrates.

PMID- 15159454
TI  - Endoplasmic reticulum stress-induced programmed cell death in soybean cells.
AB  - In animal cells, the endoplasmic reticulum may participate in programmed cell
      death by sensing and transducing apoptotic signals. In an attempt to analyze the
      role of the endoplasmic reticulum in plant programmed cell death we investigated
      the effect of cyclopiazonic acid, a specific blocker of plant endoplasmic
      reticulum-type IIA Ca2+-pumps, in soybean cells. Cyclopiazonic acid treatment
      elicited endoplasmic reticulum stress and a biphasic increase in cytosolic Ca2+
      concentration, followed by the induction of a cell death program. Cyclopiazonic
      acid-induced programmed cell death occurred with accumulation of H2O2, cytochrome
      c release from mitochondria, caspase 9- and caspase 3-like protease activation,
      cytoplasmic shrinkage and chromatin condensation. Chelation of cytosolic Ca2+
      with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethil
      ester) failed to inhibit cyclopiazonic acid-induced cell death. Taken together,
      our results provide evidence for a role of the endoplasmic reticulum and
      mitochondria in regulating cyclopiazonic acid-induced programmed cell death in
      soybean cells, probably via a cross-talk between the two organelles.

PMID- 15159455
TI  - The sequences appended to the amyloid core region of the HET-s prion protein
      determine higher-order aggregate organization in vivo.
AB  - The [Het-s] prion of the fungus Podospora anserina propagates as a self
      perpetuating amyloid form of the HET-s protein. This protein triggers a cell
      death reaction termed heterokaryon incompatibility when interacting with the HET
      S protein, an allelic variant of HET-s. HET-s displays two distinct domains, a N
      terminal globular domain and a C-terminal unstructured prion-forming domain
      (residues 218-289). Here, we describe the characterization of HET-s(157-289), a
      truncated form of HET-s bearing an extensive deletion in the globular domain but
      retaining full activity in incompatibility and prion propagation. In vitro, HET
      s(157-289) polymerizes into amyloid fibers displaying the same core region as
      full-length HET-s fibers. We have shown previously that fusions of green
      fluorescent protein (GFP) with HET-s or HET-s(218-289) form dot-like aggregates
      in vivo upon transition to the prion state. By contrast, a HET-s(157-289)/GFP
      fusion protein forms elongated fibrillar aggregates in vivo. Such elongated
      aggregates can reach up to 150 microm in length. The in vivo dynamics of these
      organized structures is analysed by time lapse microscopy. We find that the large
      elongate structures grow by lateral association of shorter fibrillar aggregates.
      When co-expressed with HET-s(157-289), full-length HET-s and HET-s(218-289) can
      be incorporated into such elongated aggregates. Together, our data indicate that
      HET-s(157-289) aggregates can adopt an organized higher-order structure in vivo
      and that the ability to adopt this supramolecular organization is conferred by
      the sequences appended to the amyloid core region.

PMID- 15159457
TI  - Opioid therapy and headache: a cause and a cure.

PMID- 15159456
TI  - Inhibition of basement membrane formation by a nidogen-binding laminin gamma1
      chain fragment in human skin-organotypic cocultures.
AB  - Basement membranes generally determine different tissue compartments in complex
      organs, such as skin, playing not only an important structural but also a
      regulatory role. We have previously demonstrated the formation of a regular
      basement membrane in organotypic three-dimensional (3D)-cocultures of human skin
      keratinocytes and fibroblasts by indirect immunofluorescence and transmission
      electron microscopy. In this assembly process, cross-linking of type IV collagen
      and the laminin gamma1 chain by nidogen is considered a crucial step. For a
      functional proof, we have now competitively inhibited nidogen binding to laminin
      in 3D-cocultures with a recombinant laminin gamma1 fragment (gamma1III3-5 module)
      spanning this binding site. Repeated treatment abolished the deposition of
      nidogen at the epithelial-matrix interface but also greatly perturbed the
      presence of other matrix constituents such as laminin and perlecan. This effect
      persisted over the entire observation period of 10 to 21 days. In contrast, some
      components of the basement membrane zone were only moderately affected, with the
      laminin-5 isoform (gamma2 chain), type IV collagen and integrin alpha6ss4 still
      showing a distinct staining at their regular position, when seen by light
      microscopy. Furthermore, epidermal morphology and differentiation remained
      largely normal as indicated by the regular location of keratins K1/K10 and also
      of late differentiation markers. Ultrastructural examination demonstrated that
      the gamma1 fragment completely suppressed any formation of basement membrane
      structures (lamina densa) and also of hemidesmosomal adhesion complexes. As a
      consequence of hemidesmosome deficiency, keratin filament bundles were not
      attached to the ventral basal cell aspect. These findings were further
      substantiated by immuno-electron microscopy, revealing either loss or drastic
      reduction and dislocation of basement membrane and hemidesmosomal components.
      Taken together, in this simplified human skin model (representing a 'closed
      system') a functional link has been demonstrated between compound structures of
      the extra- and intracellular space at the junctional zone providing a basis to
      interfere at distinct points and in a controlled fashion.

PMID- 15159458
TI  - Hemispherectomy for epilepsy: when is one half better than two?

PMID- 15159459
TI  - Improving the responsiveness of rating scales: the challenge of stepping twice
      into the same river.

PMID- 15159462
TI  - Really, most SINCERELY dead: Policy and procedure in the diagnosis of death by
      neurologic criteria.

PMID- 15159463
TI  - Daily scheduled opioids for intractable head pain: long-term observations of a
      treatment program.
AB  - BACKGROUND: Daily scheduled opioids (DSO) have been employed in some instances to
      remediate intractable headache. However, long-term studies of effectiveness,
      sequelae over several years, predictors of long-term benefit, comparisons of pain
      related outcome measures, and prevalence of problematic drug behavior are not
      available. METHODS: The authors evaluated the results of a treatment program at
      their institution designed to treat and monitor intractable headache patients
      administered DSO. Of 160 sequential patients participating in the program, 70 who
      remained on DSO for at least 3 years qualified for inclusion in an efficacy
      analysis. Patients completed structured questionnaires at each medical visit as
      part of routine clinical care. The authors assessed medical records during
      treatment, and during the 2 years before starting DSO. The primary clinical
      efficacy variable was percentage improvement in the severe headache index
      (frequency x severity of severe headaches/week). RESULTS: Analysis of the medical
      records found 41 (26%) of the original 160 patients with >50% improvement.
      Patients reported larger improvements on a visual analog scale (mean improvement
      = 70%) than shown by the medical record (mean improvement = 46%), p < 0.00001.
      Problem drug behavior (dose violations, lost prescriptions, multisourcing)
      occurred in 50% of patients, usually involving dose violations. CONCLUSIONS: For
      a select group of intractable headache patients, DSO can offer significant
      benefit. However, 74% of those treated either failed to show significant
      improvement or were discontinued from the program for clinical reasons. The
      relatively low percentage of patients with demonstrated efficacy and unexpectedly
      high prevalence of misuse have clinical relevance.

PMID- 15159460
TI  - Practice parameter: medical treatment of infantile spasms: report of the American
      Academy of Neurology and the Child Neurology Society.
AB  - OBJECTIVE: To determine the current best practice for treatment of infantile
      spasms in children. METHODS: Database searches of MEDLINE from 1966 and EMBASE
      from 1980 and searches of reference lists of retrieved articles were performed.
      Inclusion criteria were the documented presence of infantile spasms and
      hypsarrhythmia. Outcome measures included complete cessation of spasms,
      resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence
      or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles
      were selected for detailed review. Recommendations were based on a four-tiered
      classification scheme. RESULTS: Adrenocorticotropic hormone (ACTH) is probably
      effective for the short-term treatment of infantile spasms, but there is
      insufficient evidence to recommend the optimum dosage and duration of treatment.
      There is insufficient evidence to determine whether oral corticosteroids are
      effective. Vigabatrin is possibly effective for the short-term treatment of
      infantile spasm and is possibly also effective for children with tuberous
      sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic
      screening is required in patients on vigabatrin; however, the data are
      insufficient to make recommendations regarding the frequency or type of
      screening. There is insufficient evidence to recommend any other treatment of
      infantile spasms. There is insufficient evidence to conclude that successful
      treatment of infantile spasms improves the long-term prognosis. CONCLUSIONS: ACTH
      is probably an effective agent in the short-term treatment of infantile spasms.
      Vigabatrin is possibly effective.

PMID- 15159464
TI  - Use of narcotic analgesics in the emergency department treatment of migraine
      headache.
AB  - OBJECTIVE: Treatment of acute migraine headache with narcotics is potentially
      ineffective and may lead to abuse. The authors examined the treatment practice
      variation across five linked EDs in one Canadian center, focusing on the use of
      narcotic analgesics and factors associated with their use. METHODS: Five hundred
      acute migraine headache patient charts were randomly selected from five Canadian
      EDs. Charts underwent a structured review to determine medication use. Data were
      analyzed, comparing those who received narcotics as first-line treatment with
      those who did not, using chi(2) and t-tests and logistic regression. RESULTS: The
      majority of patients (59.6%) received narcotics as first-line treatment. Numerous
      factors were associated with first-line narcotic treatment. Having taken
      antiheadache medications prior to ED presentation (odds ratio [OR]: 2.63; 95% CI:
      1.53, 4.51) and hospital of presentation being other than Hospital A (e.g.,
      Hospital D, OR: 6.32; 95% CI: 2.76, 14.46) increased the odds of receiving first
      line narcotics. Having received a more urgent triage score (OR: 0.4; 95% CI:
      0.24, 0.65) or having a longer duration of headache (OR: 0.994; 95% CI: 0.99,
      0.99) decreased the odds of receiving first-line narcotics. CONCLUSIONS: Acute
      migraine management in these EDs does not meet current consensus guidelines.
      Factors associated with narcotic use are predictable, and a concerted effort to
      replace narcotics with more evidence-based first-line treatments is needed.

PMID- 15159465
TI  - Elevated levels of circulating trace amines in primary headaches.
AB  - BACKGROUND: Trace amines, including tyramine, octopamine, and synephrine, are
      closely related to classic biogenic amines. They have been hypothesized to
      promote migraines and other types of primary headaches, but there is no direct
      evidence supporting this hypothesis. METHODS: Using a multichannel
      electrochemical high-performance liquid chromatography system, the authors
      evaluated whether changes in circulating trace amines occur in subjects with
      migraine (with or without aura) during headache-free periods as well as in
      patients with cluster headache (CH) during the remission and active phases as
      compared with healthy control subjects. RESULTS: Plasma levels of all trace
      amines were significantly higher in CH patients, in both the remission and the
      active phases, when compared with control subjects or subjects with migraine. In
      addition, intraplatelet levels of octopamine, synephrine, and tyramine were
      higher in CH patients than in control subjects. In migraine patients, plasma
      levels of octopamine and synephrine were higher compared with controls, although
      in migraine with aura, the difference was not significant. CONCLUSIONS: Whereas
      the elevation of plasma trace amine levels in both migraine and CH supports the
      hypothesis that disorders of biogenic amine metabolism may be a characteristic
      biochemical trait in primary headache sufferers, the observation that such
      alterations are more prominent in patients with CH than migraine patients
      suggests that they may reflect sympathetic or hypothalamic dysfunction.

PMID- 15159466
TI  - Mirtazapine is effective in the prophylactic treatment of chronic tension-type
      headache.
AB  - BACKGROUND: The tricyclic antidepressant amitriptyline is the only drug with
      prophylactic efficacy for chronic tension-type headache. However, amitriptyline
      is only moderately effective, with headache reduction of approximately 30%, and
      treatment is often hampered by side effects. Mirtazapine is a relatively new so
      called noradrenergic and specific serotonergic antidepressant, which is more
      specific and therefore generally better tolerated. OBJECTIVE: To evaluate the
      efficacy of mirtazapine. METHODS: Twenty-four nondepressed patients with chronic
      tension-type headache were included in a randomized, double-blind, placebo
      controlled, crossover trial. All patients had tried numerous other treatments.
      Mirtazapine 15 to 30 mg/day or placebo was each given for 8 weeks separated by a
      2-week wash-out period. RESULTS: Twenty-two patients completed the study. The
      primary efficacy variable, area-under-the-headache curve (AUC; duration x
      intensity), was lower during treatment with mirtazapine (843) than during
      treatment with placebo (1,275) (p = 0.01). Mirtazapine also reduced the secondary
      efficacy variables headache frequency (p = 0.005), headache duration (p = 0.03),
      and headache intensity (p = 0.03) and was well tolerated. CONCLUSIONS:
      Mirtazapine reduced AUC by 34% more than placebo in difficult-to-treat patients.
      This finding is clinically relevant and may stimulate the development of
      prophylactic treatments with increased efficacy and fewer side effects for
      tension-type headache and other types of chronic pain.

PMID- 15159467
TI  - Cerebral hemispherectomy: hospital course, seizure, developmental, language, and
      motor outcomes.
AB  - OBJECTIVE: To compare hemispherectomy patients with different pathologic
      substrates for hospital course, seizure, developmental, language, and motor
      outcomes. METHODS: The authors compared hemispherectomy patients (n = 115) with
      hemimegalencephaly (HME; n = 16), hemispheric cortical dysplasia (hemi CD; n =
      39), Rasmussen encephalitis (RE; n = 21), infarct/ischemia (n = 27), and
      other/miscellaneous (n = 12) for differences in operative management, postsurgery
      seizure control, and antiepilepsy drug (AED) usage. In addition, Vineland
      Adaptive Behavior Scale (VABS) developmental quotients (DQ), language, and motor
      assessments were performed pre- or postsurgery, or both. RESULTS: Surgically, HME
      patients had the greatest perioperative blood loss, and the longest surgery time.
      Fewer HME patients were seizure free or not taking AEDs 1 to 5 years postsurgery,
      but the differences between pathologic groups were not significant. Postsurgery,
      66% of HME patients had little or no language and worse motor scores in the
      paretic limbs. By contrast, 40 to 50% of hemi CD children showed near normal
      language and motor assessments, similar to RE and infarct/ischemia cases. VABS DQ
      scores showed +5 points or more improvement postsurgery in 57% of patients, and
      hemi CD (+12.7) and HME (+9.1) children showed the most progress compared with RE
      (+4.6) and infarct/ischemia (-0.6) cases. Postsurgery VABS DQ scores correlated
      with seizure duration, seizure control, and presurgery DQ scores. CONCLUSIONS:
      The pathologic substrate predicted pre- and postsurgery differences in outcomes,
      with hemimegalencephaly (but not hemispheric cortical dysplasia) patients doing
      worse in several domains. Furthermore, shorter seizure durations, seizure
      control, and greater presurgery developmental quotients predicted better
      postsurgery developmental quotients in all patients, irrespective of pathology.

PMID- 15159468
TI  - Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical
      malformation.
AB  - BACKGROUND: Syndromes of bilateral symmetric polymicrogyria include an autosomal
      recessive form of bilateral frontoparietal polymicrogyria (BFPP), in which the
      malformation is most severe rostrally. The authors describe a new syndrome they
      have termed "bilateral generalized polymicrogyria" (BGP), in which the
      malformation occurs in a generalized distribution but is often most severe in the
      perisylvian regions. METHODS: Patients with bilateral polymicrogyria were
      identified from multiple medical centers worldwide. The diagnosis of BGP was
      based on findings from conventional spin echo MRI and, in one case, postmortem
      neuropathologic findings. Genetic analysis was performed for those patients from
      consanguineous pedigrees and those with multiple affected siblings to rule out
      linkage to the BFPP locus on chromosome 16q. RESULTS: Twelve patients were
      identified with BGP. Clinical features included cognitive and motor delay as well
      as seizures. Some specific features characteristic of other known bilateral
      polymicrogyria syndromes, such as pseudobulbar palsy and dysconjugate gaze, were
      not commonly seen in these patients. Radiologically, polymicrogyria appeared
      widespread but was often most severe in the perisylvian regions. Pathologic
      examination in one case revealed a diffusely thin and excessively folded cerebral
      cortex lacking normal six-layered architecture. Seven patients subjected to
      genetic analysis did not demonstrate linkage to the BFPP locus. CONCLUSIONS: BGP
      is a distinct syndrome of cortical malformation. Several features allow BGP to be
      distinguished from other disorders on the growing list of bilateral symmetric
      polymicrogyria syndromes.

PMID- 15159469
TI  - Temporal lobe volumes in patients with hippocampal sclerosis with or without
      cortical dysplasia.
AB  - BACKGROUND: Recent MRI-based volume reconstruction studies in intractable
      temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy
      that extends to the adjacent neocortical areas. OBJECTIVE: To study the extent of
      temporal lobe volume (TLV) abnormalities in patients with pathologically
      confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior
      temporal lobectomy for the treatment of drug-resistant TLE. METHODS: Fifty
      patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal
      cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI
      based TLVs and hippocampal and hemispheric volume reconstructions in all patients
      were compared between pathologic groups and with volumes acquired from 10 age
      matched control subjects. RESULTS: TLVs ipsilateral to the epileptogenic zone in
      patients with TLE were smaller than TLVs in control subjects (p < 0.01). In
      patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller
      than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p <
      0.001). In patients with right TLE, there were no significant asymmetries. The
      contralateral TLVs (regardless of the side of surgery) were smaller in the HS +
      CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/-
      6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal
      atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone,
      accounting for significantly smaller TLV/hippocampal volume ratios compared with
      patients with HS alone. CONCLUSIONS: Drug-resistant TLE due to HS is associated
      with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal
      lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe
      involvement in patients with HS and CD.

PMID- 15159470
TI  - The nature and course of neuropsychological morbidity in chronic temporal lobe
      epilepsy.
AB  - OBJECTIVE: To characterize the nature and degree of cognitive morbidity in
      patients with chronic temporal lobe epilepsy compared with healthy control
      subjects, determine the association between the duration of epilepsy and
      cognitive morbidity, and ascertain whether there are factors that moderate the
      association between duration of disorder and cognitive impairment. METHODS:
      Temporal lobe epilepsy (n = 96) and healthy control (n = 82) subjects were
      assessed with a comprehensive neuropsychological battery. Test performances were
      adjusted for age, gender, and education and transformed to a common metric (z
      scores). Analyses included group comparisons and correlations of duration of
      epilepsy with cognitive morbidity. RESULTS: Patients with temporal lobe epilepsy
      exhibited not only worse memory function (p < 0.05) but worse performance across
      measures of intelligence, language, executive function, and motor speed (p <
      0.05). Chronicity of epilepsy was related to worsening mental status (r = 0.42, p
      < 0.001). This relationship was particularly evident among those individuals with
      less (r = 0.58, p < 0.001) compared with more (r = 0.25, NS) cerebral reserve,
      operationally defined by years of formal education. CONCLUSIONS:
      Neuropsychological morbidity in chronic temporal lobe epilepsy is widespread in
      nature despite a focal epileptic process. Cross-sectional analyses demonstrate
      that increasing duration of epilepsy is associated with worsening mental status.
      Individuals with less educational attainment (low cerebral reserve) exhibit
      especially poor cognitive function in association with chronicity of epilepsy.

PMID- 15159471
TI  - Detection of electrographic seizures with continuous EEG monitoring in critically
      ill patients.
AB  - OBJECTIVE: To identify patients most likely to have seizures documented on
      continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to
      record the first seizure. METHODS: Five hundred seventy consecutive patients who
      underwent cEEG monitoring over a 6.5-year period were reviewed for the detection
      of subclinical seizures or evaluation of unexplained decrease in level of
      consciousness. Baseline demographic, clinical, and EEG findings were recorded and
      a multivariate logistic regression analysis performed to identify factors
      associated with 1) any EEG seizure activity and 2) first seizure detected after
      >24 hours of monitoring. RESULTS: Seizures were detected in 19% (n = 110) of
      patients who underwent cEEG monitoring; the seizures were exclusively
      nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures,
      89% (n = 98) were in intensive care units at the time of monitoring.
      Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI
      4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy
      (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness
      prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within
      the first 24 hours of cEEG monitoring in 88% of all patients who would eventually
      have seizures detected by cEEG. In another 5% (n = 6), the first seizure was
      recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected
      after 48 hours of monitoring. Comatose patients were more likely to have their
      first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose
      patients; OR 4.5, p = 0.018). CONCLUSIONS: CEEG monitoring detected seizure
      activity in 19% of patients, and the seizures were almost always nonconvulsive.
      Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to
      monitoring were risk factors for electrographic seizures. Comatose patients
      frequently required >24 hours of monitoring to detect the first electrographic
      seizure.

PMID- 15159472
TI  - Trigeminal afferent input alters the excitability of facial motoneurons in
      hemifacial spasm.
AB  - OBJECTIVE: To investigate whether skin or muscle afferent input via the
      trigeminal nerve alters the excitability of facial motoneurons in hemifacial
      spasm (HFS). METHODS: Botulinum toxin type A (BTX) was injected only to the
      orbicularis oculi (O. oculi) muscle of 21 patients with idiopathic HFS, and the
      excitability of the orbicularis oris (O. oris) motoneurons was monitored. The
      synkinetic response (SR) of the blink reflex and abnormal muscle response (AMR)
      were recorded from the O. oris before and after treatment. RESULTS: BTX
      injections produced marked to moderate improvement in the O. oculi of all 21
      patients and in the O. oris of 17 (81%). The rectified areas of SR1 and SR2 were
      smaller after treatment. In particular, the AMR area showed a reduction (p =
      0.02). CONCLUSIONS: The significant lessening of spasms in the O. oris after BTX
      injection to the O. oculi and the concomitant reduction in excitability of O.
      oris neurons are consistent with the hypothesis that in HFS, skin or muscle
      afferent volleys via the trigeminal nerve enhance the excitability of facial
      nerve motoneurons.

PMID- 15159473
TI  - Objective tests for upper motor neuron involvement in amyotrophic lateral
      sclerosis (ALS).
AB  - OBJECTIVE: To develop objective markers for upper motor neuron (UMN) involvement
      in ALS, the value of single-voxel MR spectroscopy (MRS) and transcranial magnetic
      stimulation (TMS) was studied. METHODS: Test results of 164 ALS patients who had
      MRS only (n = 91), TMS only (n = 13), or both (n = 60) were analyzed; also, 11
      autopsy examinations were evaluated. RESULTS: Abnormal test results consistent
      with UMN involvement were found in 134 patients with clinical UMN signs: 86% on
      MRS, 77% on TMS, and 70% on MRS and TMS together. Among 30 patients with solely
      LMN signs (progressive muscular atrophy), UMN results were found in 63% on MRS,
      63% on TMS, and 46% on both tests together. There was a significant association
      of the degree of abnormal N-acetyl aspartate/creatine ratios with UMN signs (p =
      0.01). The sensitivity to detect UMN involvement was 0.86 for MRS (specificity
      0.37) and 0.77 for TMS (specificity 0.38). At autopsy, all 11 patients had
      pathologic UMN abnormalities, including 4 with normal MRS and 1 with normal TMS
      in life. CONCLUSIONS: MRS is highly sensitive, somewhat more than TMS, and shows
      good correlation with clinical UMN signs. Combining MRS and TMS results in the
      same patient with further refinement may help in the early diagnosis of ALS.

PMID- 15159474
TI  - Increased lipid peroxidation in sera of ALS patients: a potential biomarker of
      disease burden.
AB  - BACKGROUND: Markers of oxidative stress and immune activation are significantly
      elevated in postmortem ALS CNS tissue, although the relevance to pathogenesis is
      unclear. OBJECTIVE: To determine the degree and distribution of oxidative stress
      and immune activation in living ALS patients and whether these levels correlate
      with the rate of progression or extent of disease. METHOD: Serum and CSF samples
      from sporadic ALS (sALS) patients were assayed for 4-hydroxy-2,3-nonenal (HNE), a
      lipid peroxidation product, and monocyte chemoattractant protein-1alpha (MCP
      1alpha), a beta-chemokine, by high-performance liquid chromatography and ELISA
      and compared with levels measured in disease and normal control subjects by one
      way analysis of variance. SALS serum levels were analyzed in relation to rate of
      progression, stage of disease, and drug therapy. RESULTS: HNE levels were
      significantly elevated in the sera and spinal fluid of sALS patients compared
      with control populations and positively correlated with extent of disease but not
      rate of progression. MCP-1alpha levels were also elevated in the sera of sALS
      patients, with the exception of the neurodegenerative disease control subjects,
      but decreased with advancing disease. CSF MCP-1alpha levels were not different
      between the sampled populations. There was no correlation between serum HNE and
      MCP-1alpha levels in sALS patients and extent of disease. However, an inverse
      relationship between HNE and MCP-1alpha was demonstrable in vitro. Low levels of
      HNE stimulated release of MCP-1alpha from cultured human macrophages, whereas
      high levels inhibited release of MCP-1alpha. CONCLUSIONS: These data confirm the
      presence of increased oxidative stress and immune activation in ALS patients. HNE
      is also suggested as a possible biomarker of disease.

PMID- 15159475
TI  - Disparities in perceptions of distress and burden in ALS patients and family
      caregivers.
AB  - OBJECTIVES: To examine agreement between end-stage ALS patients and their family
      caregivers on indicators of physical and psychological status at the end of life.
      METHODS: Patient-caregiver pairs completed monthly interviews in patient homes.
      Patients were asked to rate their current pain, energy, suffering, depression,
      control over ALS, optimism, interest in hastened death, weariness from ALS, will
      to live, and how burdened they thought caregivers were on Visual Analogue Scales.
      Caregivers completed identical ratings of patients as well as a measure of their
      own burden. Both independently completed the ALS Functional Rating Scale-Rev.
      (ALSFRS-R), a measure of patient disability and physical function. RESULTS: A
      total of 69 patient-caregiver pairs participated. For measures of physical
      function, kappa ranged from 0.49 to 0.83, indicating moderate to excellent
      agreement. Patient and caregiver composite ALSFRS-R scores were highly correlated
      (r = 0.92, p < 0.001). Agreement between patients and caregivers was high for
      ratings of patient pain, control over ALS, optimism, and will to live, and this
      level of agreement remained high over multiple assessments. In pairwise analyses,
      caregivers rated patients as having less energy, greater suffering, and greater
      weariness than patients indicated for themselves, whereas patients rated
      caregivers as more burdened than caregivers reported for themselves. CONCLUSIONS:
      Caregivers can accurately report information about a patient's physical function
      at the end of life. However, patients and caregivers each overestimated the
      psychosocial impact of the disease on the other.

PMID- 15159477
TI  - Expression of protein kinase C isoforms and interleukin-1beta in myofibrillar
      myopathy.
AB  - BACKGROUND: The term myofibrillar myopathy refers to a rare and clinically
      heterogeneous group of muscle disorders. The pathogenesis of this myopathy is not
      well understood. The morphologic hallmark is myofibrillar destruction with
      abnormal expression of numerous proteins, most consistently of desmin. METHODS:
      The authors investigated eight patients with myofibrillar myopathy belonging to
      four families. They studied the role of different protein kinase C isoforms and
      of interleukin-1beta, a cytokine that might activate protein kinase C and, in
      addition, mediate myofibrillar proteolysis. RESULTS: Immunohistochemical analysis
      showed the expression of alpha, eta, and zeta isoforms of protein kinase C and of
      interleukin-1beta in abnormal muscle fibers. Immunoblots confirmed the
      immunohistochemical data and revealed the absence of protein kinase C delta and
      epsilon in muscle fibers from patients and controls. CONCLUSIONS: These data
      suggest that protein kinase C and interleukin-1beta may play a role in the
      pathogenesis of myofibrillar myopathy.

PMID- 15159476
TI  - Creatine monohydrate enhances strength and body composition in Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: To determine whether creatine monohydrate (CrM) supplementation
      increases strength and fat-free mass (FFM) in boys with Duchenne muscular
      dystrophy (DD). METHODS: Thirty boys with DD (50% were taking corticosteroids)
      completed a double-blind, randomized, cross-over trial with 4 months of CrM
      (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements
      were completed of pulmonary function, compound manual muscle and handgrip
      strength, functional tasks, activity of daily living, body composition, serum
      creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary
      markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative
      stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N
      telopeptides). RESULTS: During the CrM treatment phase, there was an increase in
      handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a
      loss of global muscle strength (p = 0.056) only for the placebo phase, with no
      improvements in functional tasks or activities of daily living. Corticosteroid
      use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p <
      0.05), and CrM treatment was associated with a reduction in N-telopeptides (p <
      0.05). CONCLUSIONS: Four months of CrM supplementation led to increases in FFM
      and handgrip strength in the dominant hand and a reduction in a marker of bone
      breakdown and was well tolerated in children with DD.

PMID- 15159478
TI  - Long-term outcome of oligodendrogliomas.
AB  - BACKGROUND: Favorable prognostic factors for oligodendroglial tumors include age
      younger than 40 years, low tumor grade, and extent of resection. OBJECTIVE: To
      assess survival time and prognostic factors of 100 patients with
      oligodendrogliomas diagnosed between 1995 and 2002. METHODS: The tumors were
      rated histologically by the WHO classification as low grade (grade II) or
      anaplastic (grade III). One hundred patients were categorized into three groups:
      group A: grade II, group B: secondary grade III (low grade with anaplastic
      transformation during the follow-up), group C: de novo grade III. All patients
      were symptomatic at presentation and underwent neurosurgical procedure for
      histologic diagnosis. Follow-up was performed with clinical assessment, brain
      MRI, and MIBI scintigraphy. RESULTS: There were 66 men and 34 women (mean age at
      diagnosis 46.7 years). The most common first symptom was partial epileptic
      seizure (75%). Fifty-six patients had initial gadolinium enhancement (A: 15.6%;
      B: 36.8% as grade II, 95% as grade III; C: 90%), generally associated with MIBI
      hypermetabolism (p < 0.0001). Survival rates at 2, 5, and 10 years were A: 88%,
      88%, 85%; B: 79%, 64%, 42%; C: 43%, 16%, 15%. CONCLUSIONS: Secondary anaplastic
      oligodendroglioma patients were younger than patients with de novo anaplastic
      oligodendrogliomas. Histologic confirmation is mandatory because some low grade
      oligodendrogliomas had gadolinium enhancement on MRI and some anaplastic did not.
      Survival time was longer for secondary than for de novo anaplastic
      oligodendrogliomas without difference in the duration of the malignant phase of
      the disease.

PMID- 15159479
TI  - Primary malignant brain tumor incidence and Medicaid enrollment.
AB  - BACKGROUND: The relationship between socioeconomic status and health care
      disparities in the incidence of brain tumors is unclear. OBJECTIVE: To identify
      the associations between age, sex, and Medicaid enrollment and the incidence of
      primary malignant brain tumors in Michigan in 1996 and 1997. METHODS: Records
      were obtained from the Michigan Cancer Surveillance Program on the 1,006 incident
      cases during this period and cross-checked with Medicaid enrollment files.
      RESULTS: Persons enrolled in Medicaid were more likely than non-enrolled persons
      to develop a malignant brain tumor of any type, a glioblastoma multiforme, and an
      astrocytoma for certain subgroups. In addition, incidence rates for malignant
      brain tumors in persons enrolled in Medicaid peaked at a younger age. CONCLUSION:
      Sociodemographic status may be associated with cerebral malignancy and should be
      considered when targeting treatment and educational interventions at persons at
      risk.

PMID- 15159480
TI  - Anticipation of age at onset in multiple sclerosis: a Sardinian cohort study.
AB  - BACKGROUND: To assess the temporal trend in multiple sclerosis (MS) onset during
      the last 50 years in Sardinia, Italy. METHODS: The authors used a cohort study to
      assess age at onset in 1,513 MS patients at the MS clinic in Cagliari, all born
      and living in Sardinia. They also assessed age at onset in 41 pairs of familial
      patients from two generations and 78 pairs of affected sibs. Each familial couple
      was paired with three couples of sporadic patients born in the same year as the
      familial ones. The time interval between the first symptoms and diagnosis was
      analyzed in first and second-diagnosed patients from both familial and control
      couples. RESULTS: Mean age at onset progressively decreased from the most remote
      to the most recent decade of birth (log-rank test 778.27, p < 0.0001), being 41
      years in the former decade and 22 years in the latter. A genetic influence was
      ruled out, because the younger member of familial patients coming from two
      generations had onset 14.0 years earlier than the older one (p < 0.0001), as in
      the paired control couples (11.6 years, p < 0.0001). Moreover, mean onset in
      younger sibs was 3.4 years earlier than in older ones (p = 0.01), similar to that
      of control couples (4.1 years, p < 0.0001). CONCLUSION: Age at onset decreases
      progressively from older to younger generations in Sardinian MS patients.
      Nongenetic but recent widespread environmental changes might contribute to
      shortening of the preclinical phase-overt disease interval.

PMID- 15159481
TI  - A prospective study of Chlamydia pneumoniae infection and risk of MS in two US
      cohorts.
AB  - BACKGROUND: Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic
      agent in multiple sclerosis (MS). However, previous studies were cross-sectional
      and could not assess whether Cpn infection preceded the onset of MS. METHODS: The
      authors conducted a prospective nested case-control study among 3 million US Army
      personnel and 121,466 members of the Kaiser Permanente Medical Care Program
      (KPMCP) cohort. Serum samples collected prior to onset of MS symptoms were
      available for 83 MS cases in the Army and 46 in the KPMCP cohort. Two controls
      were matched to each case on age, sex, and date of blood collection.
      Microimmunofluorescence was used to measure serum immunoglobulin M (IgM) and
      immunoglobulin G (IgG) antibody titers to Cpn; IgG titers > or 1:16 were
      considered positive for past Cpn infection. RESULTS: Seropositivity for Cpn was
      not significantly associated with risk of MS in either cohort (Army: OR = 1.0;
      95% CI 0.6, 1.8; KPMCP: OR = 1.5; 95% CI 0.7, 3.1) or in the pooled analysis (OR
      = 1.2; 95% CI 0.8, 1.9). Serum levels of anti-Cpn IgG antibody were also not
      associated with an increased risk of MS in the Army (OR for a fourfold difference
      in antibody titers = 0.9; 95% CI 0.7, 1.2) or in the pooled analysis (OR = 1.2;
      95% CI 0.9, 1.4), but a significant increase in risk was seen in the KPMCP cohort
      (OR = 1.7; 95% CI 1.2, 2.5). The difference between these results in the Army and
      the KPMCP cohort was significant (p = 0.01). CONCLUSIONS: Neither Cpn
      seropositivity nor serum anti-Cpn IgG antibody titers predicted risk of
      developing MS. However, due to the heterogeneity of results between cohorts, we
      cannot exclude the possibility that infection with Cpn may modify the risk of MS.

PMID- 15159482
TI  - Autonomic dysfunction in dementia with Lewy bodies.
AB  - OBJECTIVE: To assess autonomic function in patients with dementia with Lewy
      bodies (DLB). METHODS: The authors compared data from 20 DLB patients evaluated
      from 1995 to 2000 to 20 age-matched multiple system atrophy (MSA) and Parkinson
      disease (PD) patients evaluated from 1999 to 2002. Analysis of variance, Fisher
      exact test, and Student t-test were applied to compare disease characteristics,
      autonomic symptoms, and function tests on the Composite Autonomic Scoring Scale
      (CASS) and Thermoregulatory Sweat Test (TST). RESULTS: In DLB, mean age at onset
      of autonomic symptoms was 70.3 +/- 8.9 years. Orthostatic symptoms were common
      and orthostatic hypotension occurred in 10/20 DLB, 17/20 MSA, and 1/20 PD
      patients (p = 0.023, 0.003). CASS-sudomotor for DLB, MSA, and PD were 1.6 +/-
      1.2, 2.5 +/- 0.7, and 0.9 +/- 0.8 (p < 0.00001). CASS-cardiovagal were 1.4 +/-
      0.9, 2.1 +/- 0.8, and 0.7 +/- 0.6 (p < 0.00001). CASS-adrenergic function were
      2.4 +/- 1.2, 3.5 +/- 0.9, and 0.5 +/- 0.6 (p < 0.00001). Total CASS were 5.2 +/-
      2.0, 8.1 +/- 1.3, and 2.2 +/- 1.2 (p < 0.00001). The most common pattern of TST
      in DLB was distal anhidrosis. Mean duration of follow-up was 3.0 +/- 1.8 years.
      Six patients needed medication to maintain blood pressure and five had good
      response. CONCLUSIONS: Autonomic dysfunction is frequent in dementia with Lewy
      bodies and the severity is intermediate between that of multiple system atrophy
      and Parkinson disease.

PMID- 15159484
TI  - Electrocardiographic Q-waves as a predictor of mortality in patients with
      cerebral infarction.
AB  - OBJECTIVE: To determine whether abnormal EKG findings could be predictive factors
      for death after a stroke event. METHODS: Patients with acute cerebral infarction
      who were 35 to 98 years old during April 1996 through November 2000 were analyzed
      (n = 216). A standard 12-lead EKG was recorded for each patient after acute
      cerebral infarction. The authors prospectively investigated the association
      between abnormal EKG findings and the risk for death after stroke over a 1-year
      period. RESULTS: Using multivariate Cox proportional hazards models, the authors
      found age (hazard ratio of mortality per year 1.10, 95% CI 1.06 to 1.15, p <
      0.001), sex (female; hazard ratio of mortality 3.42, 95% CI 1.43 to 8.19, p =
      0.006), and the presence of Q-waves in more than two leads (hazard ratio of
      mortality 2.75, 95% CI 1.23 to 6.14, p = 0.013) were independently associated
      with death after stroke. CONCLUSION: The presence of Q-waves in more than two
      leads could be a predictive factor for death after acute cerebral infarction.

PMID- 15159483
TI  - Altered neurometabolite development in HIV-infected children: correlation with
      neuropsychological tests.
AB  - BACKGROUND: HIV-infected children have abnormal cerebral metabolites, measured by
      proton MR spectroscopy ((1)H-MRS), but how these abnormalities relate to brain
      function is unclear. METHODS: Metabolite concentrations in five brain regions of
      20 HIV-infected and 13 control children were measured, and these findings were
      correlated with age, log(10) plasma viral load, CD4 count, and neuropsychological
      scores. RESULTS: Compared with control subjects, HIV patients had decreased
      choline concentration [Cho] in left frontal white matter (LFW) (-12%; p = 0.04);
      those with high viral load (>5,000 HIV RNA copies/mL) had decreased right basal
      ganglia (RBG) [Cho] (-15%; p = 0.005), and [Cr] (-13%; p = 0.02). Patients with
      high viral load also had higher [Cho] in the midfrontal gray matter (MFG) (+25%;
      p = 0.002) and lower myo-inositol [Ins] in the RBG (-18%; p = 0.04) than patients
      with low HIV viral load. N-Acetyl aspartate concentration ([NAA]) correlated with
      age in right frontal white matter (RFW) (r = 0.59, p = 0.04), LFW (r = 0.66, p =
      0.02), and right hippocampus (RHIP) (r = 0.69, p = 0.02) only in control
      subjects. In contrast, [Ins] correlated with age in both RFW and LFW (r = 0.71, p
      = 0.0006; r = 0.65, p = 0.006) only in the HIV patients. Log(10) plasma viral
      load correlated positively with [Ins] in RFW (r = 0.54, p = 0.02) and [Cho] in
      MFG (r = 0.49, p = 0.04). Compared with control subjects, HIV patients had poorer
      spatial memory (p = 0.045) and delayed spatial memory correlated with [Cho] in
      RHIP (r = 0.68, p = 0.02). CONCLUSIONS: These data suggest that normal brain
      development may be affected in children infected with HIV at birth, particularly
      evidenced by the lack of age-related increases in the neuronal marker [NAA].
      Early, aggressive treatment of infants with HIV before development of
      encephalopathy is warranted.

PMID- 15159486
TI  - Medical-legal issues in Charcot's neurologic career.
AB  - OBJECTIVE: Trace the medical-legal involvement of the 19th century clinical
      neurologist Jean-Martin Charcot. BACKGROUND: The two major neurologic concerns of
      the 1800s that involved legal questions were topics of particular academic
      interest to Charcot: post-traumatic neurologic syndromes and the behavioral
      consequences of hysteria and hypnotism. Although Charcot's medical views
      influenced several nonmedical fields, including art, poetry, and drama, his
      impact on medical-legal issues has not been examined. METHODS: Original documents
      from the Bibliotheque Charcot at the Salpetriere Hospital in Paris, legal
      documents, and publications from Charcot's era were examined. RESULTS: Although
      his involvement in medical-legal affairs was a modest element of Charcot's
      multifaceted career, he was involved in four different types of medical-legal
      activities: as a cited authority in the medical-legal literature, as an author of
      articles within medical-legal contexts, as a subpoenaed expert consultant, and as
      an expert examiner. CONCLUSIONS: Charcot's involvement demonstrates the long
      tradition of an interface between neurology and legal medicine and provides a
      model for highly limited but authoritative involvement by academic neurologists
      in medical-legal affairs.

PMID- 15159485
TI  - Heart rate dynamics predict poststroke mortality.
AB  - BACKGROUND: Impaired cardiovascular autonomic regulation assessed by heart rate
      (HR) variability provides prognostic information in patients with heart disease
      as well as among elderly. Reduced HR variability has been described in stroke
      patients, but the prognostic significance of HR variability measures after stroke
      has not been studied. METHODS: A series of 84 patients (mean age 59 +/- 12 years)
      with an acute first-ever ischemic stroke underwent a comprehensive clinical
      investigation, laboratory tests, and 24-hour EKG recordings and were followed up
      for 7 years (mean 83 +/- 54 months). Various conventional and newer qualitative
      measures of HR variability were analyzed from the baseline 24-hour EKG. Risk
      factors for all-cause mortality were assessed. RESULTS: During the follow-up, 33
      (39%) patients died and 51 survived. Among all the variables analyzed, abnormal
      long-term HR variability measure power-law slope beta (beta < -1.5), reflecting
      an altered distribution of spectral characteristics over ultra and very low
      frequency bands, was the best univariate predictor of death (hazard ratio 4.5,
      95% CI 2.2 to 9.5, p < 0.001). High age, poor Scandinavian Stroke Scale score,
      and abnormal short-term HR variability scaling measure (alpha) also predicted
      mortality in univariate analysis. In multivariate analysis, after adjustment for
      age, the only independent predictor of the risk of death was abnormal long-term
      power-law slope beta (hazard ratio 3.8, CI 1.8 to 8.2, p < 0.001). Conventional
      HR variability measures showed no prognostic power. CONCLUSION: Abnormal long
      term HR dynamics predict poststroke mortality. This measure may have value in the
      risk stratification of stroke patients.

PMID- 15159487
TI  - ALS corticospinal degeneration on DWI.

PMID- 15159488
TI  - Alpha-synuclein in blood and brain from familial Parkinson disease with SNCA
      locus triplication.
AB  - The authors recently demonstrated that genetic triplication of the SNCA locus
      causes Parkinson disease. Here it is shown that SNCA triplication results in a
      doubling in the amount of alpha-synuclein protein in blood. Examination of brain
      tissue showed a doubling in the level of SNCA message. However, at the protein
      level in brain, there was a greater effect on deposition of aggregated forms into
      insoluble fractions than on net expression of soluble alpha-synuclein.

PMID- 15159489
TI  - Spinal dural arteriovenous fistulas: long-term follow-up of 44 treated patients.
AB  - To assess the long-term clinical course of 44 patients treated for a spinal dural
      arteriovenous fistula, patients were re-examined after a median follow-up of 5.7
      years. In total, 70% of patients rated their activities of daily life as better
      or much better than before treatment. In most patients, gait disturbances and
      muscle strength had improved after treatment, with reduced disability; problems
      with micturition, defecation, and erection tended to remain unchanged.

PMID- 15159490
TI  - Exploring rating scale responsiveness: does the total score reflect the sum of
      its parts?
AB  - Evaluating rehabilitation requires rating scales that detect change. The authors
      examined Barthel Index (BI) data from 1,495 patients at a neurorehabilitation
      unit to determine whether total scale responsiveness accurately reflects item
      responsiveness. Total score effect sizes were moderate to large (0.47 to 1.09).
      Item-level effect sizes (0.13 to 1.16) reveal floor (3.5 to 82.3%) and ceiling
      (9.7 to 95.4%) effects. Results suggest BI total score effect sizes may hide item
      level weaknesses and may underestimate the impact of rehabilitation.

PMID- 15159492
TI  - Practical limitations of acute stroke MRI due to patient-related problems.
AB  - Patient-related factors may make MRI impractical in an emergency setting. The
      authors prospectively assessed the limitations on obtaining MRI in 141
      consecutive acute stroke patients. MRI was not feasible in 28 (19.9%) patients
      owing to patient-related issues. Apart from MR contraindications (n = 14; 9.9%),
      the main factors precluding MRI were a diminished level of consciousness,
      vomiting, agitation, and hemodynamic compromise. In the subgroup of patients
      ineligible for MRI because of medical reasons (n = 11), intracerebral hemorrhage
      was frequent (n = 9; 73%).

PMID- 15159491
TI  - Placebo-controlled phase I/II studies of minocycline in amyotrophic lateral
      sclerosis.
AB  - Two double-blind, randomized, placebo-controlled feasibility trials of
      minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or
      placebo for 6 months; there were no significant differences in adverse events
      (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover
      trial. The mean tolerated dose was 387 mg/day, there was a trend toward more
      gastrointestinal AE (p = 0.057), and blood urea nitrogen and liver enzymes became
      elevated (p < 0.05). Using these data, the authors have designed and launched a
      phase III trial.

PMID- 15159493
TI  - Vergence deficits in pontine lesions.
AB  - Eye movements were recorded with the search coil system in two patients to
      determine whether lesions of the pontine nuclei selectively impair vergence to
      ramp targets (slow vergence) or step targets (fast vergence). Whereas conjugate
      saccades were not different from healthy control subjects, conjugate smooth
      pursuit eye movements had a reduced gain in horizontal and vertical directions.
      Slow convergence and divergence were impaired, whereas fast vergence did not
      differ from that of control subjects. Pontine nuclei appear to be involved in the
      slow vergence control.

PMID- 15159494
TI  - Intravenous r-TPA in vertebrobasilar acute infarcts.
AB  - Presented are the clinical data of 18 consecutive patients who were treated by IV
      recombinant tissue plasminogen activator (r-TPA) for suspected vertebrobasilar
      (VB) acute ischemia within 7 hours. The mean delay for treatment was 5 +/- 3.6
      hours. Mean baseline NIH Stroke Scale score was 17 +/- 4. At 3 months, 10
      patients were independent (modified Rankin Scale [mRS] score = 0 to 2), whereas 8
      patients showed a poor outcome (mRs = 3 to 6). IV r-TPA in VB ischemia in a 7
      hour window may be safe and efficient.

PMID- 15159495
TI  - Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase
      variants.
AB  - A1A2 Na+/K+-ATPase mutations cause familial hemiplegic migraine type 2 (FHM2).
      The authors identified three putative A1A2 mutations (D718N, R763H, P979L) and
      three that await validation (P796R, E902K, X1021R). Ten to 20% of FHM cases may
      be FHM2. A1A2 mutations have a penetrance of about 87%. D718N causes frequent,
      long-lasting HM, and P979L may cause recurrent coma. D718N and P979L may
      predispose to seizures and mental retardation. A1A2 does not play a major role in
      sporadic HM; only one variant, R383H, occurred in 1 of 24 cases.

PMID- 15159496
TI  - Interaction of medial temporal lobe atrophy and white matter hyperintensities in
      AD.
AB  - The authors investigated the interaction between medial temporal lobe (MTL)
      atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They
      measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy
      was associated with an increased risk of AD (OR = 6.2), but there was no
      significant association between WMH and AD. Moreover, there was an interaction
      between MTL and WMH (p = 0.045). These results suggest that vascular and
      Alzheimer-type pathology act in synergy in the clinical syndrome of AD.

PMID- 15159497
TI  - Novel insertional presenilin 1 mutation causing Alzheimer disease with spastic
      paraparesis.
AB  - A four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer
      disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6
      nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is
      described. Serial examinations, PET scans, and autopsy revealed that the mutation
      in this highly conserved portion of PS1 causes an aggressive dementia that
      maintains the usual regional hierarchy of disease pathology while extending
      abnormalities into more widespread brain areas than typically seen in AD.

PMID- 15159498
TI  - Cholesterol and APOE genotype interact to influence Alzheimer disease
      progression.
AB  - In this retrospective analysis of 443 Alzheimer disease (AD) patients from a 30
      week tacrine trial, change in Alzheimer's Disease Assessment Scale score from
      baseline to final value was significantly associated with a total serum
      cholesterol/APOE genotype interaction. Disease progression in the no-APOE
      epsilon4 allele/high-cholesterol subgroup was greater than in the normal
      cholesterol subgroups with or without epsilon4. Cholesterol levels and APOE
      genotype may interact to affect AD progression. The results are consistent with
      preclinical data on cholesterol's effects in AD.

PMID- 15159499
TI  - Infantile Parkinsonism-dystonia and elevated dopamine metabolites in CSF.
AB  - Two girls and one boy are described, with severe infantile parkinsonism-dystonia.
      This syndrome is usually caused by endogenous dopamine deficiency but in these
      patients was associated with elevated dopamine metabolites in CSF and an unusual
      eye movement disorder: ocular flutter together with saccade initiation failure.
      Pyramidal tract signs also emerged in the course of the disease in two patients.
      This combination of symptoms and biochemical findings suggests a unique
      pathogenic mechanism.

PMID- 15159500
TI  - A new SPG4 mutation in a variant form of spastic paraplegia with congenital
      arachnoid cysts.
AB  - The clinical and genetic findings are described for 16 patients from a large
      Italian family with a variant form of hereditary spastic paraplegia and
      congenital arachnoid cysts inherited as an autosomal dominant trait. A molecular
      study has revealed a novel missense mutation, T614I, in exon 17 of SPG4, which
      may play a role in both focal cortical dysgenesis and neurodegeneration of the
      motor neurons in the corticospinal tract.

PMID- 15159502
TI  - L-2-hydroxyglutaric aciduria and brain malignant tumors: a predisposing
      condition?
AB  - L-2-hydroxyglutaric aciduria is a rare metabolic encephalopathy displaying a
      subcortical leukoencephalopathy on MRI. Diagnosis rests on detection of an
      abnormal accumulation of L-2-hydroxyglutaric acid in body fluids. The authors
      report on four patients who developed a malignant brain tumor during the course
      of the disease. This association points to a possible role of L-2-hydroxyglutaric
      aciduria in predisposing to brain tumorigenesis.

PMID- 15159503
TI  - Response of relapsed or refractory primary central nervous system lymphoma
      (PCNSL) to topotecan.
AB  - The authors treated 16 immunocompetent patients with refractory or relapsed
      primary CNS lymphoma with topotecan. Fifteen patients had been pretreated with up
      to three chemotherapy regimens, three of them additionally with whole brain
      irradiation (WBI), and one with WBI alone. Four complete remissions and two
      partial remissions were achieved. Progression-free survival was 20% at 6 months
      and 13% at 12 months.

PMID- 15159504
TI  - Autosomal dominant occipital cephalocele.
AB  - The authors report the clinical and radiographic characteristics of a non
      consanguineous Vietnamese kindred with an autosomal dominant form of occipital
      cephalocele. Affected family members all presented with occipital subscalp bulges
      at birth. Except for the proband, all individuals were developmentally normal
      with otherwise normal neurologic examinations. Unaffected family members,
      including obligate carriers, share no clinical characteristics, demonstrating
      incomplete penetrance.

PMID- 15159501
TI  - The metabolic topography of posthypoxic myoclonus.
AB  - Posthypoxic myoclonus (PHM) is a syndrome of action and intention myoclonus that
      occurs in some patients who survive a cardiac arrest. Using PET and statistical
      parametric mapping, the authors observed a significant bilateral increase in
      glucose metabolism in the ventrolateral thalamus and pontine tegmentum in
      patients relative to controls. Interventions such as deep brain stimulation that
      interrupt networks that involve these structures may be useful in patients with
      severe PHM.

PMID- 15159505
TI  - Progressive myopathy with circulating autoantibody against giantin in the Golgi
      apparatus.
AB  - A woman aged 59 years with adult-onset progressive myopathy had anti-Golgi
      (giantin) autoantibody in the serum. Limb-muscle biopsy revealed chronic myopathy
      with paucity of cellular reactions and reduced immunostaining for alpha
      dystroglycan. The similarity of the current patient with cases of hereditary
      alpha-dystroglycanopathies (Fukuyama-type congenital muscular dystrophy, Walker
      Warburg syndrome, muscle-eye-brain disease, congenital muscular dystrophy type
      1C, and limb-girdle muscular dystrophy type 2I) suggests that the Golgi apparatus
      is the target organelle in a subset of myopathies.

PMID- 15159506
TI  - Anti-ryanodine receptor antibodies and FK506 in myasthenia gravis.
AB  - Anti-ryanodine receptor (RyR) antibodies were measured in sera from 33 myasthenia
      gravis (MG) patients using three peptides from the human RyR1 sequence, two C
      terminal peptides included in the functional calcium release channel, and an N
      terminal peptide implicated in ion-conduction. Antibodies were more frequently
      positive against the two C-terminal peptides, particularly in thymoma-associated
      MG. In a preliminary open trial with FK506, immunosuppressant and enhancer of RyR
      related sarcoplasmic calcium release, the authors observed the sustained benefits
      in anti-RyR-positive MG patients.

PMID- 15159507
TI  - Initiation of an effective neurology resident ethics curriculum.
AB  - The authors' neurology residency program used a case-based curriculum developed
      by the American Academy of Neurology's Ethics, Law and Humanities Committee to
      provide a resident education course in ethics. A pretest and post-test were
      developed and administered. A survey was completed at the end of the course to
      evaluate resident satisfaction. Post-test scores improved an average of 19% and
      this increase was significant (p < 0.0004). Residents found the course useful for
      their education and the time commitment acceptable.

PMID- 15159508
TI  - Late-onset Leigh syndrome in a patient with mitochondrial complex I NDUFS8
      mutations.
AB  - Analysis of the complex I NDUFS8 gene from Leigh syndrome patients with isolated
      complex I deficiency revealed that one patient with late-onset disease and
      partial complex I defect was a compound heterozygote for two novel mutations in
      NDUFS8 gene. Western blot analysis revealed a deficiency in the NDUFS8
      polypeptide, but also reductions in other nuclear subunits of complex I,
      suggesting that this subunit is essential for either the assembly or stability of
      complex I.

PMID- 15159509
TI  - Journey of an embolus.

PMID- 15159510
TI  - Pure pandysautonomia as a complication of chronic lymphocytic leukemia.

PMID- 15159512
TI  - Chronic cough due to Thr124Met mutation in the peripheral myelin protein zero
      (MPZ gene).

PMID- 15159511
TI  - Multiple meningiomas in brain and lung due to acquired mutation of the NF2 gene.

PMID- 15159513
TI  - Vasculitic mononeuritis multiplex induced by valacyclovir.

PMID- 15159514
TI  - Lateral sinus stenoses in idiopathic intracranial hypertension resolving after
      CSF diversion.

PMID- 15159515
TI  - Undetectable CSF hypocretin-1 in "Hashimoto's encephalopathy" associated with
      coma.

PMID- 15159516
TI  - Glutathione transferase Omega class polymorphisms in Parkinson disease.

PMID- 15159517
TI  - Personal history: cross-coverage.

PMID- 15159518
TI  - VA Stroke Study: neurologist care is associated with increased testing but
      improved outcomes.

PMID- 15159519
TI  - Fatigue and depression are associated with poor quality of life in ALS.

PMID- 15159520
TI  - Impaired hemodynamics and neural activation? A fMRI study of major cerebral
      artery stenosis.

PMID- 15159521
TI  - Patient page. Treatment and quality of life for people with ALS.

PMID- 15159522
TI  - Short-term in vitro and in vivo analyses for assessing the tumor-promoting
      potentials of cigarette smoke condensates.
AB  - Previous studies found that repeated application of smoke condensate from tobacco
      burning reference cigarettes to chemically initiated SENCAR mouse skin promoted
      the development of tumors in a statistically significant and dose-dependent
      manner, while condensate from prototype cigarettes that primarily heat tobacco
      promoted statistically fewer tumors. Based on the recognized correlation between
      sustained, potentiated epidermal hyperplasia and tumor promotion, we conducted
      tests to examine the utility of selected short-term analyses for discriminating
      between condensates exhibiting significantly different promotion activities. In
      vitro analyses assessing the potential for inducing cytotoxicity (ATP
      bioluminescence) or free radical production (cytochrome c reduction, salicylate
      trapping) demonstrated significant reductions when comparing condensate collected
      from prototype cigarettes to reference condensate. Short-term in vivo analyses
      conducted within the context of a mouse skin, tumor-promotion protocol (i.e.,
      comparative measures of epidermal thickness, proliferative index, myeloperoxidase
      activity, leukocyte invasion, mutation of Ha-ras, and formation of modified DNA
      bases) provided similar results. Reference condensate induced statistically
      significant and dose-dependent increases (relative to vehicle control) for nearly
      all indices examined, while prototype condensate possessed a significantly
      reduced potential for inducing changes that we regarded as consistent with
      sustained epidermal hyperplasia and/or inflammation. Collectively, these data
      support the contention that selected short-term analyses associated with
      sustained hyperplasia and/or inflammation are capable of discriminating between
      smoke condensates with dissimilar tumor-promotion potentials. Moreover, our
      results suggest that comparative measures of proliferative index and
      myeloperoxidase activity, both possessing favorable correlation coefficients
      relative to tumor formation (i.e., > or = 0.95 after 8 or 12 weeks of promotion),
      may constitute reasonable end points for further investigation.

PMID- 15159523
TI  - Genotoxicity of motorcycle exhaust particles in vivo and in vitro.
AB  - We studied the genotoxic potency of motorcycle exhaust particles (MEP) by using a
      bacterial reversion assay and chromosome aberration and micronucleus tests. In
      the bacterial reversion assay (Ames test), MEP concentration-dependently
      increased TA98, TA100, and TA102 revertants in the presence of metabolic
      activating enzymes. In the chromosome aberration test, MEP concentration
      dependently increased abnormal structural chromosomes in CHO-K1 cells both with
      and without S9. Pretreatment with antioxidants (alpha-tocopherol, ascorbate,
      catalase, and NAC) showed varying degrees of inhibitory effect on the MEP-induced
      mutagenic effect and chromosome structural abnormalities. In the in vivo
      micronucleus test, MEP dose-dependently induced micronucleus formation in
      peripheral red blood cells after 24 and 48 h of treatment. The increase of
      micronucleated reticulocytes induced by MEP was inhibited by pretreatment with
      alpha-tocopherol and ascorbate. The fluorescence intensity of DCFH-DA-loaded CHO
      K1 cells was increased upon the addition of MEP. Our data suggest that MEP can
      induce genotoxicity through a reactive oxygen species-(ROS-) dependent pathway,
      which can be augmented by metabolic activation. Alpha-tocopherol, ascorbate,
      catalase, and NAC can inhibit MEP-induced genotoxicity, indicating that ROS might
      be involved in this effect.

PMID- 15159525
TI  - Lung tumorigenicity in A/J and rasH2 transgenic mice following mainstream tobacco
      smoke inhalation.
AB  - Hypothesizing that their respective genetic backgrounds would confer an increased
      sensitivity to lung tumorigenesis, the plausibility of selected rodent models for
      the inhalation testing of mainstream tobacco smoke (MTS) was evaluated. Strain
      A/J and rasH2 transgenic (Tg) mice were exposed to MTS from Kentucky 1R4F
      research cigarettes using either a whole-body or nose-only exposure regimen. The
      whole-body regimen consisted of a 20-week exposure period [0.200 mg wet total
      particulate matter/liter (WTPM/l), 6 h/day, 5 days/week]; nose-only dosing
      proceeded for 28 weeks [0.040, 0.125, or 0.400 mg WTPM/l, 3 h/day, 5 days/week].
      Both regimens included a 16-week recovery period. Gross and microscopic
      examinations of the lungs were used to evaluate tumor formation, with
      experimental results supporting the following conclusions: 1. Evaluation of MTS
      induced tumorigenicity based on gross evaluation versus microscopic confirmation
      provides strikingly disparate results, indicating that serial sectioning is
      necessary for a definitive assessment of lung tumors. 2. While the dosing
      regimens employed do not allow for a definitive comparison, whole-body exposure
      appeared to be more effective for inducing statistical changes in tumor
      multiplicity and incidence compared to nose-only exposure. 3. Exposure-related
      stress, evidenced as reductions in both body weight gain and background tumor
      formation, represents a potential confounder during inhalation testing of MTS
      tumorigenicity, with additional investigation warranted to validate the
      specificity of exposure-related responses. 4. Comparative findings between A/J
      and rasH2 Tg mice suggest that the former may be overly sensitive to exposure
      related stress, potentially influencing tumorigenic responses.

PMID- 15159526
TI  - Effects of natural and synthetic estrogens and various environmental contaminants
      on vitellogenesis in fish primary hepatocytes: comparison of bream (Abramis
      brama) and carp (Cyprinus carpio).
AB  - Interaction of environmental estrogens with the estrogen receptor (ER) has been
      shown in various fish species. Our objective was to compare the sensitivity of
      bream (Abramis brama) to (xeno-)estrogens with that of the carp (Cyprinus
      carpio), by measuring the effects of 17beta-estradiol (E2), estrone (E1),
      ethynylestradiol (EE2), bisphenol A (BPA), nonylphenol (NP), methoxychlor (MXCL),
      and halogenated aromatic hydrocarbons (HAHs) such as polychlorinated biphenyls
      (PCB126, PCB118), 2,3,7,8-tetrachlorodibenzo-dioxin (TCDD), and 2,3,4,7,8
      pentachlorodibenzofuran (PCDF) on vitellogenesis in primary hepatocytes.
      Comparing the EC50 values in bream hepatocytes: EE2 (0.1-0.2 microM) < E1 (0.6
      0.2 microM) < E2 (1.9 microM) with those of carp hepatocytes EE2 (0.03-0.06
      microM) < E2 (0.3 microM) approximately E1 (0.2-0.3 microM) we found differences
      in sensitivity and ranking of the estrogenic potency of E2 and E1, indicating
      interspecies differences. Exposure to BPA, NP, MXCL, and HAHs did not or only
      weakly induce vitellogenesis. Bream hepatocytes coexposed to E2 and TCDD, PCB126
      or PCDF showed a concentration-dependent inhibition of E2-induced vitellogenesis.
      IC50 (concentration of a compound that elicits 50% inhibition of E2-induced
      vitellogenesis) values determined in bream were: TCDD (0.02-0.09 nM) < PCB126
      (0.35-0.1 nM) < PCDF (2.0-0.1) and in carp were: TCDD (0.01 nM) < PCB126 (0.4
      nM). PCB118 showed no (anti-)estrogenic response. IC50 values and benchmark
      concentration for TCDD and PCB126 in bream and carp hepatocytes were in the same
      range, indicating similar sensitivity to these compounds. Due to their anti
      estrogenic capacity with benchmark-concentrations in the pM range TCDD, PCDF, and
      PCB126 may form a potential hazard for the reproductive success of fish species
      by inhibition of vitellogenesis.

PMID- 15159524
TI  - Consumption of xenoestrogen-contaminated fish during lactation alters adult male
      reproductive function.
AB  - Little information exists on the transfer of endocrine-disrupting effects through
      the food chain. The transfer of chemicals, particularly from the aquatic
      ecosystem, that can cause such effects on fish-eating predators must be
      established. Fish from the St. Lawrence River are exposed to xenoestrogens
      causing male reproductive dysfunction. The objective of this study was to
      determine if lactational exposure to contaminated fish could alter the
      development of the male reproductive system in rats. Three experimental groups
      were used: rats (dams) gavaged with (a) distilled water (control), or (b)
      homogenized fish from a reference site (Iles de la Paix) or (c) homogenized fish
      from a xenoestrogen-contaminated site (Ilet Vert). Pups were exposed via
      lactation and sampled on either day 21 (weaning) or day 91 (adults). There was no
      effect on the body weights or in the male reproductive organ weights between
      groups except for adult epididymal weight, which was significantly decreased in
      the xenoestrogen group. Adult sperm concentrations and sperm motility parameters
      were all significantly decreased in the xeonestrogen group as compared to the
      reference and control groups. Furthermore, the distribution of stages of
      spermatogenesis was altered in the xenoestrogen group, indicating an effect on
      the kinetics of spermatogenesis. Immunoreactivity of connexin43 (Cx43), a gap
      junctional protein, was markedly decreased in the seminiferous epithelium of the
      xenoestrogen group, suggesting that the intercellular coordination of testicular
      function may be affected. These data indicate that contaminants from xenoestrogen
      environments may pass through the food chain and exert effects on male
      reproductive functions.

PMID- 15159528
TI  - Human carcinogenic risk evaluation, part II: contributions of the EUROTOX
      specialty section for carcinogenesis.
AB  - There is growing recognition that carcinogenic risk extrapolation to low doses
      (and standard setting) should consider the mode of action of a given chemical. So
      far, there is agreement on distinguishing between genotoxic and nongenotoxic
      chemicals; yet, further differentiations seem appropriate. For genotoxic
      carcinogens, case studies of chemicals point to many possibilities for assessing
      carcinogenic risk. There are numerous, apparently genotoxic carcinogens where
      practical thresholds are a matter of discussion. For instance, positive data of
      chromosomal effects only, in the absence of mutagenicity, may support the
      characterization of a compound that produces carcinogenic effects only at high,
      toxic doses. There is a wide consensus that for non-DNA-reactive genotoxicants,
      such as aneugens, thresholds should be defined. Specific mechanisms of
      clastogenicity have been repeatedly addressed as also having thresholds, such as
      topoisomerase II poisons, or mechanisms based on reactive oxygen. These and other
      arguments together lead to the distinction of four groups of carcinogens, which
      have been introduced (C. Streffer et al., 2004, Springer-Verlag). There are
      nonthreshold genotoxic carcinogens (for low-dose risk assessment, the linear
      nonthreshold [LNT] model appears appropriate); genotoxic carcinogens, for which
      the existence of a threshold cannot be sufficiently supported (in these cases the
      LNT model is used as a default assumption, based on the scientific uncertainty
      and backed by the precautionary principle); genotoxic carcinogens for which a
      practical threshold is supported; and nongenotoxic carcinogens and non-DNA
      reactive carcinogens (for these compounds a true [perfect] threshold is
      associated with a clearly founded no-observed-adverse-effect level).

PMID- 15159527
TI  - N-ethyl-N-nitrosourea (ENU) increased brain mutations in prenatal and neonatal
      mice but not in the adults.
AB  - The incidence of childhood cancer is increasing. One of the most common cancers
      for children under 15 years of age, gliomas for example, has been reported to
      have increased in incidence over the last 20 years by approximately 40%. The
      rising trend of childhood cancer in brain may be associated with environmental
      exposure to genotoxins and susceptibility to mutation in early development. To
      investigate age-dependent mutagenic sensitivity of brain tissue to genotoxins,
      the Big Blue mouse model was utilized in this study. Groups of five male mice
      were treated with a single dose of 120 mg/kg ENU transplacentally at three days
      before birth (prenatal), eight days (neonate) or eighteen weeks (adult) after
      birth. The animals were sacrificed six weeks after the treatment. The mutant
      frequencies and types of mutations in the brain cII gene from ENU-treated and
      concurrent control mice were determined. A significant increase in mutant
      frequencies over control was found in the prenatal and neonatal groups whereas
      there was no significant difference between the adult group and its control.
      Molecular analysis of the mutants also indicated that the mutational spectra from
      the ENU-treated mice were age-dependent. The percentage of A:T --> T:A
      transversion, the typical type of mutation induced by ENU, was inversely related
      to the treatment age, whereas G:C --> A:T transition was the main type of
      mutation in the adult group, the same as the control. These results demonstrate a
      differential mutagenic effect of ENU on the mouse brain depending on the stages
      of development and suggest an enhanced susceptibility of brain cancer hazard for
      perinatal exposure to genotoxicants.

PMID- 15159529
TI  - Biography of Pietro De Camilli.

PMID- 15159530
TI  - Programmable cells: interfacing natural and engineered gene networks.
AB  - Novel cellular behaviors and characteristics can be obtained by coupling
      engineered gene networks to the cell's natural regulatory circuitry through
      appropriately designed input and output interfaces. Here, we demonstrate how an
      engineered genetic circuit can be used to construct cells that respond to
      biological signals in a predetermined and programmable fashion. We employ a
      modular design strategy to create Escherichia coli strains where a genetic toggle
      switch is interfaced with: (i) the SOS signaling pathway responding to DNA
      damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio
      fischeri. The genetic toggle switch endows these strains with binary response
      dynamics and an epigenetic inheritance that supports a persistent phenotypic
      alteration in response to transient signals. These features are exploited to
      engineer cells that form biofilms in response to DNA-damaging agents and cells
      that activate protein synthesis when the cell population reaches a critical
      density. Our work represents a step toward the development of "plug-and-play"
      genetic circuitry that can be used to create cells with programmable behaviors.

PMID- 15159531
TI  - T4 replication: what does "processivity" really mean?

PMID- 15159533
TI  - Environmental signatures in proteome properties.

PMID- 15159532
TI  - Nitrous oxide (N(2)O) requires the N-methyl-D-aspartate receptor for its action
      in Caenorhabditis elegans.
AB  - Nitrous oxide (N(2)O, also known as laughing gas) and volatile anesthetics (VAs),
      the original and still most widely used general anesthetics, produce anesthesia
      by ill-defined mechanisms. Electrophysiological experiments in vertebrate neurons
      have suggested that N(2)O and VAs may act by distinct mechanisms; N(2)O
      antagonizes the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors,
      whereas VAs alter the function of a variety of other synaptic proteins. However,
      no genetic or pharmacological experiments have demonstrated that any of these in
      vitro actions are responsible for the behavioral effects of either class of
      anesthetics. By using genetic tools in Caenorhabditis elegans, we tested whether
      the action of N(2)O requires the NMDA receptor in vivo and whether its mechanism
      is shared by VAs. Distinct from the action of VAs, N(2)O produced behavioral
      defects highly specific and characteristic of that produced by loss-of-function
      mutations in both NMDA and non-NMDA glutamate receptors. A null mutant of nmr-1,
      which encodes a C. elegans NMDA receptor, was completely resistant to the
      behavioral effects of N(2)O, whereas a non-NMDA receptor-null mutant was normally
      sensitive. The N(2)O-resistant nmr-1(null) mutant was not resistant to VAs.
      Likewise, VA-resistant mutants had wild-type sensitivity to N(2)O. Thus, the
      behavioral effects of N(2)O require the NMDA receptor NMR-1, consistent with the
      hypothesis formed from vertebrate electrophysiological data that a major target
      of N(2)O is the NMDA receptor.

PMID- 15159534
TI  - Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin
      A-mediated intestinal inflammation.
AB  - Clostridium difficile, the causative agent of antibiotic-associated colitis,
      mediates inflammatory diarrhea by releasing toxin A, a potent 308-kDa
      enterotoxin. Toxin A-induced inflammatory diarrhea involves many steps, including
      mucosal release of substance P (SP) corticotropin-releasing hormone (CRH) and
      neutrophil transmigration. Here we demonstrate that, compared with wild type,
      mice genetically deficient in CRH (Crh(-/-)) have dramatically reduced ileal
      fluid secretion, epithelial cell damage, and neutrophil transmigration 4 h after
      intraluminal toxin A administration. This response is associated with diminished
      mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of
      wildtype mice. In wild-type mice, toxin A stimulates an increase in intestinal SP
      content compared with buffer administration. In contrast, toxin A administration
      in Crh(-/-) mice fails to result in an increased SP content. Moreover,
      immunohistochemical experiments showed that CRH and SP are colocalized in some
      enteric nerves of wild-type mice, and this colocalization is more evident after
      toxin A administration. These results provide direct evidence for a major
      proinflammatory role for CRH in the pathophysiology of enterotoxin-mediated
      inflammatory diarrhea and indicate a SP-linked pathway.

PMID- 15159535
TI  - Structural basis for the attachment of a paramyxoviral polymerase to its
      template.
AB  - The nucleocapsid of measles virus is the template for viral RNA synthesis and is
      generated through packaging of the genomic RNA by the nucleocapsid protein (N).
      The viral polymerase associates with the nucleocapsid through a small, trihelical
      binding domain at the carboxyl terminus of the phosphoprotein (P). Translocation
      of the polymerase along the nucleocapsid during RNA synthesis is thought to
      involve the repeated attachment and release of the binding domain. We have
      investigated the interaction between the binding domain from measles P (amino
      acids 457-507) and the sequence it recognizes within measles N (amino acids 477
      505). By using both solution NMR spectroscopy and x-ray crystallography, we show
      that N(487-503) binds as a helix to the surface created by the second (alpha2)
      and third (alpha3) helices of P(457-507), in an orientation parallel to the helix
      alpha3, creating a four-helix bundle. The binding interface is tightly packed and
      dominated by hydrophobic amino acids. Binding and folding of N(487-503) are
      coupled. However, when not bound to P, N(487-503) does not resemble a statistical
      random coil but instead exists in a loosely structured state that mimics the
      bound conformation. We propose that before diffusional encounter, the ensemble of
      accessible conformations for N(487-503) is biased toward structures capable of
      binding P, facilitating rapid association of the two proteins. This study
      provides a structural analysis of polymerase-template interactions in a
      paramyxovirus and presents an example of a protein-protein interaction that must
      be only transiently maintained as part of its normal function.

PMID- 15159536
TI  - Gene knockout of glycine transporter 1: characterization of the behavioral
      phenotype.
AB  - N-methyl-d-aspartate receptor (NMDAR) activation requires both the binding of
      glutamate to its recognition site and occupancy of the strychnine insensitive
      glycine modulatory site (GMS). Pharmacological studies suggest that the glycine
      transporter, GlyT1, maintains subsaturating concentrations of glycine at synaptic
      NMDARs. To characterize further the role of GlyT1, we generated mice in which the
      gene encoding GlyT1 was inactivated by homologous recombination through insertion
      of a PGK-Neo cassette in place of exons 2 and 3. Real-time quantitative PCR
      revealed no transcripts in newborn homozygous [GlyT1(-/-)] mice and a 50%
      reduction in heterozygous (HZ) [GlyT1(+/-)] mice as compared with WT littermates.
      The activity of Na(+)-dependent glycine transport in forebrain homogenates was
      similarly affected. Homozygous mice died within 12 h of birth. In acute
      hippocampal slices, exogenous glycine or d-serine (10 microM) enhanced NMDAR
      currents with Schaffer collateral stimulation in WT mice but not HZ mice,
      suggesting that the GMS was more occupied in the latter. The NMDAR/alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor ratio of the excitatory
      postsynaptic currents was significantly increased in the HZ mice. In the water
      maze, the HZ mice exhibited better spatial retention. Furthermore, HZ mice were
      less sensitive to an amphetamine disruption of prepulse inhibition than WT mice
      but were more sensitive to the effects of MK-801. Thus, reduced expression of
      GlyT1 enhances hippocampal NMDAR function and memory retention and protects
      against an amphetamine disruption of sensory gating, suggesting that drugs which
      inhibit GlyT1 might have both cognitive enhancing and antipsychotic effects.

PMID- 15159537
TI  - An actin-like gene can determine cell polarity in bacteria.
AB  - Achieving proper polarity is essential for cellular function. In bacteria, cell
      polarity has been observed by using both morphological and molecular markers;
      however, no general regulators of bacterial cell polarity have been identified.
      Here we investigate the effect on cell polarity of two cytoskeletal elements
      previously implicated in cell shape determination. We find that the actin-like
      MreB protein mediates global cell polarity in Caulobacter crescentus, although
      the intermediate filament-like CreS protein influences cell shape without
      affecting cell polarity. MreB is organized in an axial spiral that is dynamically
      rearranged during the cell cycle, and MreB dynamics may be critical for the
      determination of cell polarity. By examining depletion and overexpression
      strains, we demonstrate that MreB is required both for the polar localization of
      the chromosomal origin sequence and the dynamic localization of regulatory
      proteins to the correct cell pole. We propose that the molecular polarity
      inherent in an actin-like filament is translated into a mechanism for directing
      global cell polarity.

PMID- 15159538
TI  - Lysine fortification reduces anxiety and lessens stress in family members in
      economically weak communities in Northwest Syria.
AB  - Lysine is a limiting amino acid in diets based on wheat as the staple. In
      experimental animals, prolonged dietary lysine inadequacy increases stress
      induced anxiety. If observed in humans, such a result would have a strong
      implication for the relationship between nutrition and communal quality of life
      and mental health. As part of a 3-month randomized double-blind study, we tested
      whether lysine fortification of wheat reduces anxiety and stress response in
      family members in poor Syrian communities consuming wheat as a staple food. In
      the lysine-fortified group, the plasma cortisol response to the blood drawing as
      a cause of stress was reduced in females, as was sympathetic arousal in males as
      measured by skin conductance. Lysine fortification also significantly reduced
      chronic anxiety as measured by the trait anxiety inventory in males. These
      results suggest that some stress responses in economically weak populations
      consuming cereal-based diets can be improved with lysine fortification.

PMID- 15159539
TI  - Stereoisomer libraries: total synthesis of all 16 stereoisomers of the pine
      sawfly sex pheromone by a fluorous mixture-synthesis approach.
AB  - All 16 stereoisomers of the sex pheromone of pine sawfly (3,7,11
      trimethylundecanol propanoate ester) have been synthesized on a 10- to 20-mg
      scale by a split-parallel fluorous mixture-synthesis approach. Spectral data
      obtained for all 32 compounds (16 alcohols and the corresponding propionates)
      matched well with published data, thereby validating the fluorous-tag encoding of
      diastereoisomers. This fluorous-tag encoding method is recommended for the
      efficient synthesis of multiple stereoisomers for spectroscopic studies,
      biological tests, or other structure-function relationships.

PMID- 15159540
TI  - Voluntary exercise increases axonal regeneration from sensory neurons.
AB  - Recent advances in understanding the role of neurotrophins on activity-dependent
      plasticity have provided insight into how behavior can affect specific aspects of
      neuronal biology. We present evidence that voluntary exercise can prime adult
      dorsal root ganglion neurons for increased axonal regeneration through a
      neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase
      in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of
      exercise compared with sedentary animals. Neurite length over 18-22 h in culture
      correlated directly with the distance that animals ran. The exercise-conditioned
      animals also showed enhanced regrowth of axons after an in vivo nerve crush
      injury. Sensory ganglia from the 3- and 7-day-exercised animals contained higher
      brain-derived neurotrophic factor, neurotrophin 3, synapsin I, and GAP43 mRNA
      levels than those from sedentary animals. Consistent with the rise in brain
      derived neurotrophic factor and neurotrophin 3 during exercise, the increased
      growth potential of the exercise-conditioned animals required activation of the
      neurotrophin signaling in vivo during the exercise period but did not require new
      mRNA synthesis in culture.

PMID- 15159541
TI  - Crystal structure of the Deinococcus radiodurans single-stranded DNA-binding
      protein suggests a mechanism for coping with DNA damage.
AB  - Single-stranded DNA (ssDNA)-binding (SSB) proteins are uniformly required to bind
      and protect single-stranded intermediates in DNA metabolic pathways. All
      bacterial and eukaryotic SSB proteins studied to date oligomerize to assemble
      four copies of a conserved domain, called an oligonucleotide/oligosaccharide
      binding (OB) fold, that cooperate in nonspecific ssDNA binding. The vast majority
      of bacterial SSB family members function as homotetramers, with each monomer
      contributing a single OB fold. However, SSB proteins from the Deinococcus-Thermus
      genera are exceptions to this rule, because they contain two OB folds per
      monomer. To investigate the structural consequences of this unusual arrangement,
      we have determined a 1.8-A-resolution x-ray structure of Deinococcus radiodurans
      SSB. The structure shows that D. radiodurans SSB comprises two OB domains linked
      by a beta-hairpin motif. The protein assembles a four-OB-fold arrangement by
      means of symmetric dimerization. In contrast to homotetrameric SSB proteins,
      asymmetry exists between the two OB folds of D. radiodurans SSB because of
      sequence differences between the domains. These differences appear to reflect
      specialized roles that have evolved for each domain. Extensive crystallographic
      contacts link D. radiodurans SSB dimers in an arrangement that has important
      implications for higher-order structures of the protein bound to ssDNA. This
      assembly utilizes the N-terminal OB domain and the beta-hairpin structure that is
      unique to Deinococcus and Thermus species SSB proteins. We hypothesize that
      differences between D. radiodurans SSB and homotetrameric bacterial SSB proteins
      may confer a selective advantage to D. radiodurans cells that aids viability in
      environments that challenge genomic stability.

PMID- 15159542
TI  - A high-affinity interaction between NusA and the rrn nut site in Mycobacterium
      tuberculosis.
AB  - The bacterial NusA protein enhances transcriptional pausing and termination and
      is known to play an essential role in antitermination. Antitermination is
      signaled by a nut-like cis-acting RNA sequence comprising boxB, boxA, and boxC.
      In the present study, we demonstrate a direct, specific high-affinity interaction
      between the rrn leader nut-like sites and the NusA proteins of Mycobacterium
      tuberculosis and Escherichia coli. This NusA-RNA interaction relies on the
      conserved region downstream of boxA, the boxC region, thus demonstrating a key
      function of this element. We have established an in vivo assay for
      antitermination in mycobacteria and use this to show that the M. tuberculosis rrn
      nut-like site enhances transcriptional read-through of untranslated RNA
      consistent with an antitermination signal within this site. Finally, we present
      evidence that this NusA-RNA interaction affects transcriptional events further
      downstream.

PMID- 15159543
TI  - Lethality to human cancer cells through massive chromosome loss by inhibition of
      the mitotic checkpoint.
AB  - A compromised mitotic checkpoint, the primary mechanism for ensuring that each
      new cell receives one copy of every chromosome, has been implicated as a
      contributor to carcinogenesis. However, a checkpoint response is shown here to be
      essential for cell survival, including that of chromosomally instable colorectal
      cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in
      human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell
      death within six divisions except when cytokinesis is also inhibited. Thus,
      suppression of mitotic checkpoint signaling is invariably lethal as the
      consequence of massive chromosome loss, findings that have implications for
      inhibiting proliferation of tumor cells.

PMID- 15159544
TI  - Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in
      leucine biosynthesis.
AB  - The leucine biosynthetic pathway is essential for the growth of Mycobacterium
      tuberculosis and is a potential target for the design of new anti-tuberculosis
      drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes
      the first committed step in this pathway, has been determined by multiwavelength
      anomalous dispersion methods and refined at 2.0-A resolution in complex with its
      substrate alpha-ketoisovalerate. The structure reveals a tightly associated,
      domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM
      barrel catalytic domain, a helical linker domain, and a regulatory domain of
      novel fold. Mutational and crystallographic data indicate the latter as the site
      for leucine feedback inhibition of activity. Domain swapping enables the linker
      domain of one monomer to sit over the catalytic domain of the other, inserting
      residues into the active site that may be important in catalysis. The alpha
      ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity
      that can accommodate acetyl-CoA. Sequence and structural similarities point to a
      catalytic mechanism similar to that of malate synthase and an evolutionary
      relationship with an aldolase that catalyzes the reverse reaction on a similar
      substrate.

PMID- 15159545
TI  - The distribution of fitness effects caused by single-nucleotide substitutions in
      an RNA virus.
AB  - Little is known about the mutational fitness effects associated with single
      nucleotide substitutions on RNA viral genomes. Here, we used site-directed
      mutagenesis to create 91 single mutant clones of vesicular stomatitis virus
      derived from a common ancestral cDNA and performed competition experiments to
      measure the relative fitness of each mutant. The distribution of nonlethal
      deleterious effects was highly skewed and had a long, flat tail. As expected,
      fitness effects depended on whether mutations were chosen at random or reproduced
      previously described ones. The effect of random deleterious mutations was well
      described by a log-normal distribution, with -19% reduction of average fitness;
      the effects distribution of preobserved deleterious mutations was better
      explained by a beta model. The fit of both models was improved when combined with
      a uniform distribution. Up to 40% of random mutations were lethal. The proportion
      of beneficial mutations was unexpectedly high. Beneficial effects followed a
      gamma distribution, with expected fitness increases of 1% for random mutations
      and 5% for preobserved mutations.

PMID- 15159546
TI  - NMDA receptor hypofunction produces concomitant firing rate potentiation and
      burst activity reduction in the prefrontal cortex.
AB  - Cognitive deficits associated with frontal lobe dysfunction are a determinant of
      long-term disability in schizophrenia and are not effectively treated with
      available medications. Clinical studies show that many aspects of these deficits
      are transiently induced in healthy individuals treated with N-methyl-D-aspartate
      (NMDA) antagonists. These findings and recent genetic linkage studies strongly
      implicate NMDA receptor deficiency in schizophrenia and suggest that reversing
      this deficiency is pertinent to treating the cognitive symptoms of schizophrenia.
      Despite the wealth of behavioral data on the effects of NMDA antagonist treatment
      in humans and laboratory animals, there is a fundamental lack of understanding
      about the mechanisms by which a general state of NMDA deficiency influences the
      function of cortical neurons. Using ensemble recording in freely moving rats, we
      found that NMDA antagonist treatment, at doses that impaired working memory,
      potentiated the firing rate of most prefrontal cortex neurons. This potentiation,
      which correlated with expression of behavioral stereotypy, resulted from an
      increased number of irregularly discharged single spikes. Concurrent with the
      increase in spike activity, there was a significant reduction in organized
      bursting activity. These results identify two distinct mechanisms by which NMDA
      receptor deficiency may disrupt frontal lobe function: an increase in
      disorganized spike activity, which may enhance cortical noise and transmission of
      disinformation; and a decrease in burst activity, which reduces transmission
      efficacy of cortical neurons. These findings provide a physiological basis for
      the NMDA receptor deficiency model of schizophrenia and may clarify the nature of
      cortical dysfunction in this disease.

PMID- 15159547
TI  - Comparative mapping and marker-assisted selection in Rosaceae fruit crops.
AB  - The development of saturated linkage maps using transferable markers, restriction
      fragment length polymorphisms, and micro-satellites has provided a foundation for
      fruit tree genetics and breeding. A Prunus reference map with 562 such markers is
      available, and a further set of 13 maps constructed with a subset of these
      markers has allowed genome comparison among seven Prunus diploid (x = 8) species
      (almond, peach, apricot, cherry, Prunus ferganensis, Prunus davidiana, and Prunus
      cerasifera); marker colinearity was the rule with all of them. Preliminary
      results of the comparison between apple and Prunus maps suggest a high level of
      synteny between these two genera. Conserved genomic regions have also been
      detected between Prunus and Arabidopsis. By using the data from different linkage
      maps anchored with the reference Prunus map, it has been possible to establish,
      in a general map, the position of 28 major genes affecting agronomic characters
      found in different species. Markers tightly linked to the major genes responsible
      for the expression of important traits (disease/pest resistances, fruit/nut
      quality, self-incompatibility, etc.) have been developed in apple and Prunus and
      are currently in use for marker-assisted selection in breeding programs.
      Quantitative character dissection using linkage maps and candidate gene
      approaches has already started. Genomic tools such as the Prunus physical map,
      large EST collections in both Prunus and Malus, and the establishment of the map
      position of high numbers of ESTs are required for a better understanding of the
      Rosaceae genome and to foster additional research and applications on fruit tree
      genetics.

PMID- 15159549
TI  - Protein kinase CK2 modulates developmental functions of the abscisic acid
      responsive protein Rab17 from maize.
AB  - The maize abscisic acid responsive protein Rab17 is a highly phosphorylated late
      embryogenesis abundant protein involved in plant responses to stress. In this
      study, we provide evidence of the importance of Rab17 phosphorylation by protein
      kinase CK2 in growth-related processes under stress conditions. We show the
      specific interaction of Rab17 with the CK2 regulatory subunits CK2 beta-1 and CK2
      beta-3, and that these interactions do not depend on the phosphorylation state of
      Rab17. Live-cell fluorescence imaging of both CK2 and Rab17 indicates that the
      intracellular dynamics of Rab17 are regulated by CK2 phosphorylation. We found
      both CK2 beta subunits and Rab17 distributed over the cytoplasm and nucleus. By
      contrast, catalytic CK2 alpha subunits and a Rab17 mutant protein (mRab17) that
      is not a substrate for CK2 phosphorylation remain accumulated in the nucleoli. A
      dual-color image shows that the CK2 holoenzyme accumulates mainly in the nucleus.
      The importance of Rab17 phosphorylation in vivo was assessed in transgenic
      plants. The overexpression of Rab17, but not mRab17, arrests the process of seed
      germination under osmotic stress conditions. Thus, the role of Rab17 in growth
      processes is mediated through its phosphorylation by protein kinase CK2.

PMID- 15159548
TI  - Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine
      cells.
AB  - Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an
      important role in exocytosis. Several potential effectors of Rab3, including
      rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2
      was identified originally in endocrine pancreas as a molecule homologous to
      rabphilin3, but its role in exocytosis is unclear. To clarify the physiological
      function of Noc2 directly, we have generated Noc2 knockout (Noc2(-/-)) mice.
      Glucose intolerance with impaired insulin secretion was induced in vivo by acute
      stress in Noc2(-/-) mice, but not in wild-type (Noc2(+/+)) mice. Ca(2+)-triggered
      insulin secretion from pancreatic isles of Noc2(-/-) mice was markedly impaired,
      but was completely restored by treatment with pertussis toxin, which inhibits
      inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of
      clonidine, an alpha(2)-adrenoreceptor agonist, on insulin secretion was
      significantly greater in Noc2(-/-) islets than in Noc2(+/+) islets. Impaired
      Ca(2+)-triggered insulin secretion was rescued by adenovirus gene transfer of
      wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3.
      Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas
      by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required
      for the effect. Interestingly, we also found a marked accumulation of secretory
      granules in various exocrine cells of Noc2(-/-) mice, especially in exocrine
      pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of
      Rab3, is essential in normal regulation of exocytosis in both endocrine and
      exocrine cells.

PMID- 15159551
TI  - Suppressive activity of protease inhibitors from buckwheat seeds against human T
      acute lymphoblastic leukemia cell lines.
AB  - The buckwheat protease inhibitor designated BWI-1, a member of the potato
      inhibitor I family, inhibits trypsin, chymotrypsin, and subtilisin, whereas the
      buckwheat protease inhibitor designated BWI-2a, a novel protease inhibitor
      homologous to the vicilin family, inhibits only trypsin. We examined the
      suppressive activity of BWI-1 and BWI-2a against T-acute lymphoblastic leukemia
      (T-ALL) cells, such as JURKAT and CCRF-CEM, and human normal blood lymphocytes.
      Both inhibitors significantly suppressed the growth of T-ALL cells as judged by
      the soluble 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (tetrazolium/formazan assay). JURKAT cells showed slightly higher susceptibility
      to buckwheat inhibitors than CCRF-CEM cells. Modification of Arg residue(s) in
      inhibitors by 1,2-cyclohexandione inactivated their trypsin inhibitory activity,
      considerably abolishing their suppressive activity. This suggests that the
      trypsin inhibitory activity is involved in the suppression of growth of human T
      ALL cell lines. It was further found that both inhibitors triggered programmed
      cell death (apoptosis) of these cell strains with DNA fragmentation.

PMID- 15159550
TI  - 3D structure of human FK506-binding protein 52: implications for the assembly of
      the glucocorticoid receptor/Hsp90/immunophilin heterocomplex.
AB  - FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl
      isomerase activity, is an important immunophilin involved in the heterocomplex of
      steroid receptors with heat-shock protein 90. Here we report the crystal
      structures of two overlapped fragments [N(1-260) and C(145-459)] of FKBP52 and
      the complex with a C-terminal pentapeptide from heat-shock protein 90. Based on
      the structures of these two overlapped fragments, the complete putative structure
      of FKBP52 can be defined. The structure of FKBP52 is composed of two consecutive
      FKBP domains, a tetratricopeptide repeat domain and a short helical domain beyond
      the final tetratricopeptide repeat motif. Key structural differences between
      FKBP52 and FKBP51, including the relative orientations of the four domains and
      some important residue substitutions, could account for the differential
      functions of FKBPs.

PMID- 15159552
TI  - Influence of carbon and nitrogen sources and temperature on hyperproduction of a
      thermotolerant beta-glucosidase from synthetic medium by Kluyveromyces marxianus.
AB  - The effect of carbon source and its concentration, inoculum size, yeast extract
      concentration, nitrogen source, pH of the fermentation medium, and fermentation
      temperature on beta-glucosidase production by Kluyveromyces marxianus in shake
      flask culture was investigated. These were the independent variables that
      directly regulated the specific growth and beta-glucosidase production rate. The
      highest product yield, specific product yield, and productivity of beta
      glucosidase occurred in the medium (pH 5.5) inoculated with 10% (v/v) inoculum of
      the culture. Cellobiose (20 g/L) significantly improved beta-glucosidase
      production measured as product yield (YP/S) and volumetric productivity (QP)
      followed by sucrose, lactose, and xylose. The highest levels of productivity (144
      IU/[L.h]) of beta-glucosidase occurred on cellobiose in the presence of CSL at 35
      degrees C and are significantly higher than the values reported by other
      researchers on almost all other organisms. The thermodynamics and kinetics of
      beta-glucosidase production and its deactivation are also reported. The enzyme
      was substantially stable at 60 degrees C and may find application in some
      industrial processes.

PMID- 15159553
TI  - Noncompetitive enzyme immunoassay for alpha-fetoprotein using flow injection
      chemiluminescence.
AB  - A novel, direct noncompetitive flow injection enzyme immunoassay for alpha
      fetoprotein (AFP) was developed by enhanced chemiluminescence detection. The
      method was based on off-line incubation of AFP and horseradish peroxidase (HRP)
      labeled anti-AFP, and then trapping of the unbound enzyme conjugate by an
      immunoaffinity column filled with AFP-modified Sepharose. The immunocomplex
      formed in incubation passed through the column and then was directly detected by
      a postcolumn chemiluminescence technique. The optimal conditions for the
      immunoassay procedure and chemiluminescence detection were established. At a 1:10
      dilution of enzyme conjugate solution, the linear range for chemiluminescence
      detection of AFP was from 2.0 to 75 ng/mL with a correlation coefficient of 0.993
      and a coefficient of variation of 2.67% at 30 ng/mL. The detection limit was 0.5
      ng/mL. This method was flexible, sensitive, and rapid. The immunoaffinity column
      of 200 microL could be repeatedly used 100 times without a single decrease. The
      whole assay time including the preincubation step was only 30 min for one sample.

PMID- 15159554
TI  - Dilute-acid pretreatment of corn stover using a high-solids percolation reactor.
AB  - Pretreatment of corn stover by dilute sulfuric acid was investigated using a
      laboratory percolation (flowthrough) reactor operated under high-solids
      conditions. The effects of reaction conditions and operating parameters on the
      performance of the percolation reactor were investigated seeking the optimal
      range in which acceptable levels of yield and sugar concentration could be
      attained. It was demonstrated that 70-75% recovery of xylose and 6 to 7% (w/w)
      xylose concentration were attainable. The high sugar concentration was obtained
      as a result of dense packing of dry corn stover and the low liquid throughput.
      Xylose was mostly unreacted, rather than decomposed. The cellulose and the
      unreacted xylan of treated corn stover were both effectively hydrolyzed by a
      "cellulase" enzyme preparation that also exhibits some activity on xylan. The
      xylose yield was affected significantly by the flow rate under the same reaction
      time and conditions. This behavior appears to be related to sugar decomposition,
      mass transfer resistance, and the fact that acid is neutralized by the buffering
      components of the biomass.

PMID- 15159555
TI  - The "Bringer" strategy: a very fast and highly efficient method for construction
      of mutant libraries by error-prone polymerase chain reaction of ring-closed
      plasmids.
AB  - Random mutagenesis constitutes a keystone in many strategies of directed
      evolution of biocatalysts and is often done by error-prone polymerase chain
      reaction (epPCR). Traditionally, the epPCR-generated DNA fragments are then
      subcloned into an expression vector to obtain a mutant library, which in turn is
      transformed into a suited host and screened for mutants that display the desired
      property. However, the vast majority of epPCR-generated fragments generally are
      lost during the subcloning step, making it the bottleneck in the mutant library
      construction procedure. Here we report a rapid and convenient strategy based on
      the epPCR amplification of a ring-closed expression plasmid that contains the
      gene of interest; after a DpnI digest the product of the epPCR reaction
      constitutes the mutant library and can be used directly for screening procedures.
      Primers binding to the beta-lactamase gene were chosen to allow application of
      the strategy to as broad a range of target plasmids as possible. The
      functionality of this approach was demonstrated by mutating the alpha-peptide
      coding region of the lacZ gene.

PMID- 15159556
TI  - Interaction of an intermediate structure of Bacillus subtilis alpha-amylase with
      alkyl-substituted sepharose 4B: a model of membrane translocation.
AB  - An intermediate form of alpha-amylase from Bacillus subtilis was prepared
      following a previously reported procedure. Stabilization of this protein
      structure by various additives and its interaction with alkyl-substituted
      Sepharose 4B (Sepharose-lipid), used to mimic the role of the alkyl chains of the
      phospholipid bilayer, were investigated. Exposure of hydrophobic clusters in the
      protein structure on denaturation was indicated by a greater affinity of the
      intermediate form for interaction with the alkyl chains on the matrix, as
      compared with the original native structure. Near- and far-ultraviolet circular
      dichroism studies supported loss of tertiary structure with retention of
      secondary structure, as expected from molten globular intermediate forms. Based
      on the results presented, we suggest that interaction of a protein in its native
      and nonnative forms with an alkyl-substituted matrix may provide useful
      information regarding its capacity for insertion into and translocation across
      the biologic membrane.

PMID- 15159557
TI  - Accurate rocking-curve measurements on protein crystals grown in a homogeneous
      magnetic field of 2.4 T.
AB  - Differences in mosaicity between lysozyme crystals grown inside and outside a
      homogeneous magnetic field of 2.4 T and with and without agarose gel were
      investigated by X-ray diffraction rocking-curve measurements. High angular
      resolution was achieved using an Si(113) four-reflection Bartels monochromator.
      The results show that (i) all crystals were highly perfect, (ii) the mosaicities
      were clearly anisotropic and (iii) the mosaicities varied more strongly within
      each group of crystals (grown under identical conditions) than the average values
      across groups. In particular, the effect of the magnetic field on crystal
      mosaicity was found to be very small. Finally, the spatial distribution of mosaic
      blocks inside a protein crystal was visualized with a novel diffraction technique
      using a high spatial resolution two-dimensional CCD detector.

PMID- 15159558
TI  - Azospirillum irakense pectate lyase displays a toroidal fold.
AB  - The three-dimensional structure of Azospirillum irakense pectate lyase (PelA) has
      been determined at a resolution of 2.65 A. The crystals are hexagonal, belonging
      to space group P6(5)22, with unit-cell parameters a = b = 85.37, c = 231.32
      angstroms. Phase information was derived from a multiple-wavelength anomalous
      dispersion (MAD) experiment using a Hg derivative. Refinement of the model
      converged to Rcryst = 20.08% and Rfree = 25.87%. The overall structure of PelA
      does not adopt the characteristic parallel beta-helix fold displayed by pectate
      lyases from polysaccharide lyase (PL) families PL1, PL3 and PL9. Instead, it
      displays a predominantly alpha-helical structure with irregular coils and short
      beta-strands, similar to the recently reported structure of the catalytic module
      of the Cellvibrio japonicus pectate lyase Pel10Acm. The topologies of the two
      structures have been compared. They show two 'domains' with the interface between
      them being a wide-open central groove in which the active site is located. The
      active sites of the crystal structures are also compared and their similarities
      and differences are discussed.

PMID- 15159559
TI  - Short hydrogen bonds in photoactive yellow protein.
AB  - Eight high-resolution crystal structures of the ground state of photoactive
      yellow protein (PYP) solved under a variety of conditions reveal that its
      chromophore is stabilized by two unusually short hydrogen bonds. Both Tyr42 Oeta
      and Glu46 Oepsilon are separated from the chromophore phenolate oxygen by less
      than the sum of their atomic van der Waals radii, 2.6 angstroms. This is
      characteristic of strong hydrogen bonding, in which hydrogen bonds acquire
      significant covalent character. The hydrogen bond from the protonated Glu46 to
      the negatively charged phenolate oxygen is 2.58 +/- 0.01 angstroms in length,
      while that from Tyr42 is considerably shorter, 2.49 +/- 0.01 angstroms. The E46Q
      mutant was solved to 0.95 angstroms resolution; the isosteric mutation increased
      the length of the hydrogen bond from Glx46 to the chromophore by 0.29 +/- 0.01
      angstroms to that of an average hydrogen bond, 2.88 +/- 0.01 angstroms. The very
      short hydrogen bond from Tyr42 explains why mutating this residue has such a
      severe effect on the ground-state structure and PYP photocycle. The effect of
      isosteric mutations on the photocycle can be largely explained by the alterations
      to the length and strength of these hydrogen bonds.

PMID- 15159560
TI  - A benzoic acid inhibitor induces a novel conformational change in the active site
      of Influenza B virus neuraminidase.
AB  - Owing to the highly conserved nature of its active site, Influenza B virus
      neuraminidase (NA) has emerged as a major target for the design of novel anti
      influenza drugs. A benzene-ring scaffold has been used in place of the pyranose
      ring of sialic acid to develop simpler NA inhibitors that contain a minimal
      number of chiral centers. A new compound belonging to this series, BANA 207,
      showed significant improvement in inhibitory activity against Influenza B virus
      NA compared with its parent compound. Here, the structural analysis of a complex
      of BANA 207 with influenza virus B/Lee/40 NA is reported. The results indicate
      that BANA 207 forms an unexpected interaction with the crucial active-site
      residue Glu275 that stabilizes the side chain of this residue in a conformation
      previously unobserved in NA-inhibitor complexes. This change in the side-chain
      orientation of Glu275 alters the topology of the triglycerol pocket, which
      accommodates an additional lipophilic substitution at the benzene ring and may
      provide an explanation for the increased activity of BANA 207 against Influenza B
      virus NA.

PMID- 15159561
TI  - Phasing in the presence of severe site-specific radiation damage through dose
      dependent modelling of heavy atoms.
AB  - The case of a brominated RNA crystal structure determination in which standard
      three-wavelength MAD phasing was unsuccessful because of fast X-ray-induced
      debromination was reinvestigated [Ennifar et al. (2002), Acta Cryst. D58, 1262
      1268]. It was found that if the data are kept unmerged and if a dose-stamp is
      associated with each reflection measurement, dose-dependent occupancies can be
      refined for the Br atoms. Such a parametrization has been implemented in the
      macromolecular phasing program SHARP. Refining such dose-dependent occupancies on
      an unmerged data set gave a dramatic improvement, even for SAD phases from only
      the first wavelength (peak), and resulted in a good electron-density map after
      solvent flattening. The adverse effect of radiation damage has been turned into a
      beneficial one. The crucial difference is made by the use of unmerged data:
      phasing power is generated through the intensity differences of symmetry-related
      reflections recorded at different doses, i.e. corresponding to different states
      of the X-ray-induced debromination. This approach should prove useful in all
      situations of experimental phasing where site-specific radiation damage occurs
      unavoidably and undesirably and not only in cases in which radiation damage is
      purposely being created in order to demonstrate its potential usefulness.

PMID- 15159562
TI  - More rapid evaluation of biomacromolecular crystals for diffraction experiments.
AB  - The parameters used to evaluate biomacromolecular crystal quality [Rmerge,
      I/sigma(I), maximum resolution and mosaicity] strongly depend on the experimental
      diffraction conditions. In this paper, the distinctive features of the relative
      Wilson plot method are described and it is shown that the overall B factor
      obtained from this plot is more appropriate for the characterization of protein
      crystals. The relative Wilson plot has been applied to the characterization of
      crystals of the B-DNA decamer d(CCATTAATGG) and crystals of the proteins DsrD
      (dissimilatory sulfite reductase D) and hen egg-white lysozyme (HEWL), which were
      studied by neutron diffraction. It was found that the crystal quality of the B
      DNA decamer and DsrD depended significantly on the regions of the crystallization
      phase diagram from which the samples were taken. However, in the case of HEWL
      crystal quality appears to be independent of the region of the crystallization
      phase diagram.

PMID- 15159563
TI  - Structural determination of a partially hemihedrally twinned actin crystal.
AB  - An orthorhombic actin crystal (space group P2(1)2(1)2(1), unit-cell parameters a
      = 101.6, b = 103.0, c = 127.0 angstroms) was converted into a partially
      hemihedrally twinned tetragonal crystal (space group P4(3), unit-cell parameters
      a = b = 101.5, c = 104.2 angstroms) by induced condensation. This condensation
      (decrease in the c axis) was caused by the flash-freezing of the crystal, with
      30% PEG 400 as a cryoprotectant, prior to data collection. Diffraction data for
      the twinned tetragonal crystal were collected at 100 K to 3.0 angstroms
      resolution (99.8% completeness with an Rsym of 8.1%) using synchrotron radiation.
      The hemihedral twinning of the data was observed by self-rotation function
      analysis and was determined to have a partial twin fraction of 0.376 from
      intensity statistics. The structure, with two actin molecules in the
      crystallographic asymmetric unit, was determined by molecular-replacement methods
      and refined to an R factor of 0.193. As a consequence of the crystal lattice
      transformation from the orthorhombic P2(1)2(1)2(1) to the tetragonal P4(3) space
      group, actin-actin contacts were rearranged and an inter-actin dimer disulfide
      bond (Cys374) observed in the orthorhombic crystal form was broken in the
      tetragonal crystal form.

PMID- 15159564
TI  - Structure of concanavalin A at pH 8: bound solvent and crystal contacts.
AB  - Concanavalin A has been crystallized in the presence of the ligand (6-S-beta-D
      galactopyranosyl-6-thio)-cyclomaltoheptaose. The crystals are isomorphous to
      those reported for ConA complexed with peptides at low resolution (3.00-2.75
      angstroms). The structure was solved at 1.9 angstroms, with free R and R values
      of 0.201 and 0.184, respectively. As expected, no molecules of the ligand were
      bound to the protein. Soaking in the cryobuffer left its fingerprint as 25
      molecules of glycerol in the bound solvent, most of them at specific positions.
      The fact that a glycerol molecule is located in the sugar-binding pocket of each
      of the four subunits in the asymmetric unit and another is located in two of the
      peptide-binding sites suggests a recognition phenomenon rather than a
      displacement of water molecules by glycerol. Crystal contact analysis shows that
      a relation exists between the residues that form hydrogen bonds to other
      asymmetric units and the space group: contact Asp58-Ser62 is a universal feature
      of ConA crystals, while Ser66-His121, Asn69-Asn118 and Tyr100-His205 contacts are
      general features of the C222(1) crystal form.

PMID- 15159565
TI  - A subgroup algorithm to identify cross-rotation peaks consistent with non
      crystallographic symmetry.
AB  - Molecular replacement (MR) often plays a prominent role in determining initial
      phase angles for structure determination by X-ray crystallography. In this paper,
      an efficient quaternion-based algorithm is presented for analyzing peaks from a
      cross-rotation function in order to identify model orientations consistent with
      proper non-crystallographic symmetry (NCS) and to generate proper NCS-consistent
      orientations missing from the list of cross-rotation peaks. The algorithm, CRANS,
      analyzes the rotation differences between each pair of cross-rotation peaks to
      identify finite subgroups. Sets of rotation differences satisfying the subgroup
      axioms correspond to orientations compatible with the correct proper NCS. The
      CRANS algorithm was first tested using cross-rotation peaks computed from
      structure-factor data for three test systems and was then used to assist in the
      de novo structure determination of dihydrofolate reductase-thymidylate synthase
      (DHFR-TS) from Cryptosporidium hominis. In every case, the CRANS algorithm runs
      in seconds to identify orientations consistent with the observed proper NCS and
      to generate missing orientations not present in the cross-rotation peak list. The
      CRANS algorithm has application in every molecular-replacement phasing effort
      with proper NCS.

PMID- 15159567
TI  - The role of CAPS buffer in expanding the crystallization space of the nucleotide
      binding domain of the ABC transporter haemolysin B from Escherichia coli.
AB  - Nucleotide-binding domains (NBDs), which are roughly 27 kDa in size, are
      conserved components of the large family of ABC (ATP-binding cassette)
      transporters, which includes importers and exporters. NBDs, or ABC-ATPases,
      supply energy for the translocation of a vast range of substrates across
      biological membranes. Despite their hydrophilic sequence, many NBDs readily
      associate in some way with membranes but demonstrate extreme instability in
      solution upon separation from the complete transporter. Conditions that
      stabilized the purified ABC domain of the Escherichia coli haemolysin A (HlyA)
      transporter were developed. This allowed the screening of unlimited
      crystallization conditions in the presence of different substrates, the
      performance of reproducible functional assays and the protection of 50 mg ml(-1)
      protein from precipitation on ice for months. As a result, it became possible to
      obtain crystals of HlyB-NBD in the presence of ADP and ATP that were suitable for
      X-ray analysis. Although the focus of these investigations was placed on HlyB
      NBD, the strategy described here can be directly transferred to other proteins
      that display instability in solution.

PMID- 15159568
TI  - Structural effects of radiation damage and its potential for phasing.
AB  - A detailed analysis of radiation-damage-induced structural and intensity changes
      is presented on the model protein thaumatin. Changes in reflection intensities
      induced by irradiation display a parabolic character. The most pronounced
      structural changes observed were disulfide-bond breakage and associated main
      chain and side-chain movements as well as decarboxylation of aspartate and
      glutamate residues. The structural changes induced on the sulfur atoms were
      successfully used to obtain high-quality phase estimates via an RIP procedure.
      Results obtained with ACORN suggest that the contribution originating from the
      partial structure may play an important role in phasing even at less than atomic
      resolution.

PMID- 15159566
TI  - Structure of the molybdenum-cofactor biosynthesis protein MoaB of Escherichia
      coli.
AB  - The moaABC operon of Escherichia coli is involved in early steps of the
      biosynthesis of the molybdenum-binding cofactor molybdopterin, but the precise
      functions of the cognate proteins are not known. The crystal structure of the
      MoaB protein from E. coli was determined by multiple anomalous dispersion at 2.1
      angstroms A resolution and refined to an R factor of 20.4% (Rfree = 25.0%). The
      protein is a 32-symmetric hexamer, with the monomers consisting of a central beta
      sheet flanked by helices on both sides. The overall fold of the monomer is
      similar to those of the MogA protein of E. coli, the G-domains of rat and human
      gephyrin and the G-domains of Cnx1 protein from A. thaliana, all of which are
      involved in the insertion of an unknown molybdenum species into molybdopterin to
      form the molybdenum cofactor. Furthermore, the MoaB protein shows significant
      sequence similarity to the cinnamon protein from Drosophila melanogaster. In
      addition to other functions, all these proteins are involved in the biosynthesis
      of the molybdenum cofactor and have been shown to bind molybdopterin. The close
      structural homology to MogA and the gephyrin and Cnx1 domains suggests that MoaB
      may bind a hitherto unidentified pterin compound, possibly an intermediate in
      molybdopterin biosynthesis.

PMID- 15159569
TI  - Structure analysis of PH1161 protein, a transcriptional activator TenA homologue
      from the hyperthermophilic archaeon Pyrococcus horikoshii.
AB  - The crystal structure of the Bacillus subtilis TenA-homologue protein PH1161 from
      the hyperthermophilic archaebacterium Pyrococcus horikoshii was determined. TenA
      is known to belong to a new family of activators that stimulate the production of
      extracellular proteases in B. subtilis. A sequence-similarity search revealed
      that TenA-homologue proteins are widespread in bacteria and archaea, suggesting
      that this family of proteins plays an essential role in these organisms. In the
      present study, the first three-dimensional structure of a member of the TenA
      family of proteins was determined, unexpectedly revealing that the protein has a
      fold identical to that of haem oxygenase-1. Analysis has also shown that the
      protein has a unique ligand-binding pocket. Electron density of a bound ligand
      molecule was observed in this pocket. These results provide a valuable insight
      into the functional understanding of the TenA family of proteins.

PMID- 15159571
TI  - Purification, partial characterization, crystallization and preliminary X-ray
      diffraction of two cysteine-rich secretory proteins from Naja atra and
      Trimeresurus stejnegeri venoms.
AB  - Cysteine-rich secretory proteins (CRISPs) are widely distributed in mammals and
      snake venoms. They possess apparent homology but varying functions. The structure
      of CRISPs has remained elusive. Two novel members of the family, natrin and
      stecrisp, have been purified from Naja atra and Trimeresurus stejnegeri venoms,
      respectively. Their crystals diffract X-rays to resolution limits of 2.1 and 1.6
      angstroms, respectively, and belong to the orthorhombic system with different
      space groups, unit-cell parameters and numbers of molecules per asymmetric unit.
      Their structures will contribute a structural basis for further functional
      studies of this family.

PMID- 15159572
TI  - Crystallization and preliminary crystallographic analysis of SMase I, a
      sphingomyelinase from Loxosceles laeta spider venom.
AB  - SMase I, a 32 kDa sphingomyelinase found in Loxosceles laeta venom, is
      responsible for the major pathological effects of spider envenomation. This toxin
      has been cloned and functionally expressed as a fusion protein containing a 6 x
      His tag at its N-terminus to yield a 33 kDa protein [Fernandes-Pedrosa et al.
      (2002), Biochem. Biophys. Res. Commun. 298, 638-645]. The recombinant protein
      possesses all the biological properties ascribed to the whole L. laeta venom,
      including dermonecrotic and complement-dependent haemolytic activities. Dynamic
      light-scattering experiments conducted at 291 K demonstrate that the sample
      possesses a monomodal distribution, with a hydrodynamic radius of 3.57 nm. L.
      laeta SMase I was crystallized by the hanging-drop vapour-diffusion technique
      using the sparse-matrix method. Single crystals were obtained using a buffer
      solution consisting of 0.08 M HEPES and 0.9 M trisodium citrate, which was
      titrated to pH 7.5 using 0.25 M sodium hydroxide. Complete three-dimensional
      diffraction data were collected to 1.8 angstroms at the Laboratorio Nacional de
      Luz Sincrotron (LNLS, Campinas, Brazil). The crystals belong to the hexagonal
      system (space group P6(1) or P6(5)), with unit-cell parameters a = b = 140.6, c =
      113.6 angstroms. A search for heavy-atom derivatives has been initiated and
      elucidation of the crystal structure is currently in progress.

PMID- 15159570
TI  - Harvesting the high-hanging fruit: the structure of the YdeN gene product from
      Bacillus subtilis at 1.8 angstroms resolution.
AB  - High-throughput (HT) protein crystallography is severely impeded by the
      relatively low success rate of protein crystallization. Proteins whose structures
      are not solved in the HT pipeline owing to attrition in any phase of the project
      are referred to as the high-hanging fruit, in contrast to those proteins that
      yielded good-quality crystals and crystal structures, which are referred to as
      low-hanging fruit. It has previously been shown that proteins that do not
      crystallize in the wild-type form can have their surfaces engineered by site
      directed mutagenesis in order to create patches of low conformational entropy
      that are conducive to forming intermolecular interactions. The application of
      this method to selected proteins from the Bacillus subtilis genome which failed
      to crystallize in the HT mode is now reported. In this paper, the crystal
      structure of the product of the YdeN gene is reported. Of three prepared double
      mutants, i.e. E124A/K127A, E167A/E169A and K88A/Q89A, the latter gave high
      quality crystals and the crystal structure was solved by SAD at 1.8 angstroms
      resolution. The protein is a canonical alpha/beta hydrolase, with an active site
      that is accessible to solvent.

PMID- 15159573
TI  - Crystallization and preliminary X-ray crystallographic analysis of the DNA
      binding domain of BldD from Streptomyces coelicolor A3(2).
AB  - The N-terminal DNA-binding domain of BldD from Streptomyces coelicolor A3(2) was
      crystallized by the hanging-drop vapour-diffusion method at 296 K. A 1.8
      angstroms data set has been collected using synchrotron radiation at Pohang Light
      Source, South Korea. The crystal belongs to the monoclinic space group C2, with
      unit-cell parameters a = 77.2, b = 31.8, c = 33.6 angstroms, beta = 105.1
      degrees. Analysis of the packing density shows that the asymmetric unit probably
      contains one molecule, with a solvent content of 43.6%.

PMID- 15159574
TI  - Crystallization and preliminary crystallographic data of SnoaL, a polyketide
      cyclase in nogalamycin biosynthesis.
AB  - Nogalonic acid methyl ester cyclase (SnoaL) catalyzes the last ring-closure step
      in the biosynthesis of the polyketide antibiotic nogalamycin. Crystals of a
      complex of SnoaL with the substrate nogalonic acid methyl ester have been
      obtained using PEG 4000 as precipitant. The crystals are orthorhombic, space
      group I222, with unit-cell parameters a = 69.1, b = 72.0, c = 65.4 angstroms.
      They diffract to 1.35 angstroms resolution using synchrotron radiation. A
      Matthews coefficient of 2.0 angstroms3 Da(-1) suggests one subunit in the
      asymmetric unit. Diffraction data for an isomorphous uranium derivative were
      collected and a difference Patterson map showed strong peaks which allowed
      determination of the position of the uranium ions.

PMID- 15159575
TI  - Purification, characterization and preliminary crystallographic studies of a
      novel plant defensin from Pachyrrhizus erosus seeds.
AB  - Defensins are small cysteine-rich antimicrobial peptides that are widely
      distributed in plants, insects and mammals. As potent defenders in protecting
      plants from pathogenic fungal attack, plant defensins are presumed to play an
      important role in the innate immunity of plants and are expected to find
      applications in the production of transgenic crops. A novel plant defensin
      protein SPE10 from Pachyrrhizus erosus seeds was purified and partially
      sequenced. Crystallization screening using the hanging-drop vapour-diffusion
      method resulted in two crystal forms, from one of which a diffraction data set
      was collected to 0.98 A resolution. The crystal belongs to space group P2(1),
      with unit-cell parameters a = 32.71, b = 28.11, c = 54.85 angstroms, beta =
      103.78 degrees. Preliminary crystallographic studies revealed two subunits in the
      asymmetric unit.

PMID- 15159576
TI  - Expression, purification and crystallization of two peroxisomal acyl-CoA oxidases
      from Arabidopsis thaliana.
AB  - Two members of the acyl-CoA oxidase family from Arabidopsis thaliana have been
      cloned, overexpressed, purified and crystallized. Long-chain-specific acyl-CoA
      oxidase 1 crystals are characterized by a large variation in diffraction quality
      and non-isomorphous unit-cell parameters. The best crystals diffract to 2.0
      angstrom using synchrotron radiation, have unit-cell parameters a = 85.2, b =
      117.0, c = 131.0 angstrom, alpha = beta = gamma = 90 degrees and show
      P2(1)2(1)2(1) symmetry. There are two polypeptide chains in the asymmetric unit.
      Short-chain-specific acyl-CoA oxidase 4 crystals are trigonal, space group
      P3(1)21/P3(2)21, with unit-cell parameters a = b = 198.7, c = 149.6 angstroms.
      The crystals are most likely to contain six polypeptide chains in the asymmetric
      unit. Freshly prepared acyl-CoA oxidase 4 crystals diffract to 3.9 angstroms at
      cryogenic temperature at beamline I711, Max-Lab, but the diffraction quality
      degenerates after storage for only a few days in the crystallization drop. A
      selenomethionine-substituted form of the protein was produced and two-wavelength
      MAD data were collected at beamline BW7A, EMBL Outstation, Hamburg.

PMID- 15159577
TI  - Overexpression, purification and crystallization of PhzA, the first enzyme of the
      phenazine biosynthesis pathway of Pseudomonas fluorescens 2-79.
AB  - Phenazines are broad-spectrum antibiotic metabolites produced by organisms such
      as Pseudomonas and Streptomyces. Phenazines have been shown to enhance microbial
      competitiveness and the pathogenic potential of the organisms that synthesize
      them. PhzA (163 residues, approximate molecular weight 18.7 kDa) is the product
      of the first of seven genes of the operon responsible for phenazine biosynthesis
      in P. fluorescens 2-79. This enzyme is thought to catalyse one of the final steps
      in the formation of phenazine-1-carboxylic acid, the end product of phenazine
      biosynthesis in P. fluorescens 2-79. Here, the purification and crystallization
      of recombinant PhzA are reported. Crystals diffracting to 2.1 angstroms were
      obtained using 1.6 M magnesium sulfate and 2-morpholinoethanesulfonic acid
      monohydrate (MES) buffer pH 5.2-5.6. Crystals of both native and seleno-L
      methionine-labelled protein belong to the orthorhombic space group P2(1)2(1)2(1),
      with unit-cell parameters a = 66.8, b = 75.3, c = 84.5 angstroms. The asymmetric
      unit contains one dimer of PhzA.

PMID- 15159578
TI  - Crystallization of CcdB in complex with a GyrA fragment.
AB  - Plasmid addiction systems consist of a plasmid-encoded toxin-antidote pair that
      serves to stabilize low-copy-number plasmids in bacterial populations. CcdB, the
      toxin from the ccd system on the Escherichia coli F plasmid, acts as a gyrase
      poison. A 14 kDa fragment of gyrase, GyrA14, was found to bind to the toxin CcdB
      with an affinity of 1.75 x 10(-8) M. Crystals of the (GyrA14)(2) dimer in its
      free state belong to space group P4(3)2(1)2, with unit-cell parameters a = 86.4,
      c = 89.4 angstroms, and diffract to 2.4 angstroms. Crystals of the (GyrA14)(2)
      (CcdB)(2) complex belong to space group P2(1)2(1)2(1), with a = 52.1, b = 83.3, c
      = 110.9 angstroms, and diffract to 2.8 angstroms resolution.

PMID- 15159579
TI  - Cloning, purification, crystallization and preliminary crystallographic analysis
      of acylphosphatase from Pyrococcus horikoshii OT3.
AB  - Acylphosphatase is one of the smallest enzymes and catalyzes the hydrolysis of
      the carboxy-phosphate bond. An extremely thermostable acylphosphatase from a
      hyperthermophilic archaea, Pyrococcus horikoshii OT3, has been cloned, expressed
      in Escherichia coli, purified and crystallized using the sitting-drop vapour
      diffusion method with potassium/sodium tartrate as the precipitant at pH 5.5. X
      ray diffraction data have been collected to a highest resolution of 1.72
      angstroms on a synchrotron-radiation source. The crystals belong to space group
      P3(2)21, with approximate unit-cell parameters a = b = 86.6, c = 75.4 angstroms
      and two monomers in the asymmetric unit.

PMID- 15159580
TI  - Expression, purification and preliminary X-ray diffraction analysis of a
      ketoreductase from a type II polyketide synthase.
AB  - Polyketide metabolites produced by bacteria and other organisms include
      antibiotics, anticancer and antifungal compounds. In type II polyketide
      synthesis, three enzymes are sufficient to form a polyketide product of the
      requisite chain length, although the fidelity of the first cyclization is
      variable. Addition of ketoreductase (KR) to this system results in the formation
      of a product with correct cyclization and reduction. This paper reports the
      cloning of the Streptomyces coelicolor actIII ORF5 gene that codes for the
      ketoreductase. The 261-amino-acid protein has been overexpressed with a 20
      residue His tag, purified by affinity chromatography and crystallized in space
      group P3(2)21, with unit-cell parameters a = b = 103.9, c = 123.1 angstroms. The
      crystals diffract to 2.5 angstroms resolution. A complete data set has been
      collected and structure solution and refinement is under way.

PMID- 15159581
TI  - Crystallization and preliminary crystallographic analysis of a novel haemolytic
      lectin from the mushroom Laetiporus sulphureus.
AB  - The novel haemolytic lectin from the parasitic mushroom Laetiporus sulphureus
      (LSL) is a homotetramer (approximately 140 kDa) composed of subunits associated
      by non-covalent bonds. It exhibits haemagglutination and haemolytic activities,
      both of which are inhibited by N-acetyllactosamine. The structural similarity
      found between LSL and the bacterial pore-forming toxins mosquitocidal toxin
      (MTX2) from Bacillus sphaericus and alpha-toxin from Clostridium septicum points
      to a mechanism of biological action involving the formation of pores in the
      target membranes. LSL has been crystallized using the hanging-drop vapour
      diffusion method at 291 K. Diffraction-quality hexagonal crystals have unit-cell
      parameters a = b = 101.8, c = 193.9 angstroms and belong to space group P6(3)22.
      A 2.7 angstroms native data set was collected with an Rmerge of 9.2%.

PMID- 15159582
TI  - Overproduction, crystallization and preliminary crystallographic analysis of a
      novel human DNA-repair enzyme that recognizes oxidative DNA damage.
AB  - DNA glycosylases repair oxidative DNA damage caused by free radicals. Recently,
      NEIL1, a human homolog of Escherichia coli DNA glycosylase endonuclease VIII, has
      been identified and shown to exhibit broad substrate specificity for a variety of
      types of pyrimidine-base damage. An active C-terminal deletion construct of NEIL1
      was overexpressed in E. coli and crystallized. The unliganded NEIL1 crystallizes
      in space group R3, with unit-cell parameters a = b = 132.2, c = 51.1 A. Complete
      data sets were collected from native, selenomethionyl and iodinated NEIL1 to 2.1,
      2.3 and 2.4 angstroms, respectively.

PMID- 15159583
TI  - Crystallization and preliminary crystallographic analysis of an Enterococcus
      faecalis repressor protein, CylR2, involved in regulating cytolysin production
      through quorum-sensing.
AB  - CylR2 is one of two regulatory proteins associated with the quorum-sensing
      dependent synthesis of cytolysin in the common pathogen Enterococcus faecalis.
      The protein was expressed with a C-terminal six-histidine tag and purified to
      homogeneity with a cobalt-affinity column followed by size-exclusion
      chromatography. Both native and SeMet proteins were produced and crystallized.
      Complete X-ray diffraction data sets were collected from a native crystal, which
      diffracted to 2.3 angstroms resolution, and a SeMet crystal, which diffracted to
      2.1 angstroms. The crystals were tetragonal, belonging to space group P4(1) or
      P4(3), with unit-cell parameters a = b = 66.2, c = 40.9 angstroms, alpha = beta =
      gamma = 90 degrees. Based on the calculated Matthews coefficient of 2.6
      angstroms3 Da(-1) as well as analysis of anomalous difference Patterson maps, the
      asymmetric unit most likely contains two molecules of CylR2.

PMID- 15159584
TI  - Crystallization and preliminary X-ray diffraction analysis of a thermostable endo
      1,5-alpha-L-arabinanase from Bacillus thermodenitrificans TS-3.
AB  - A thermostable endo-1,5-alpha-L-arabinanase ABN-TS from Bacillus
      thermodenitrificans TS-3 with a molecular weight of 35 kDa was crystallized by
      the hanging-drop vapour-diffusion method using sodium citrate as a precipitant.
      The crystals were loop-mounted in a cryoprotectant solution containing 28%(w/v)
      sucrose and 1 M sodium citrate pH 6.0 and flash-cooled. Sucrose was selected as
      the most suitable cryoprotectant. The crystal belonged to the orthorhombic space
      group P2(1)2(1)2(1), with unit-cell parameters a = 40.3, b = 77.8, c = 89.7
      angstroms. The calculated VM based on one molecule per asymmetric unit was 2.0
      angstroms3 Da(-1). A complete data set from a frozen crystal was collected to 1.9
      angstroms resolution using synchrotron radiation at SPring-8. A molecular
      replacement solution was obtained using the structure of alpha-arabinanase 43A
      from Cellvibrio japonicus.

PMID- 15159585
TI  - Crystallization and preliminary crystallographic analysis of Bacillus subtilis
      guanine deaminase.
AB  - Guanine deaminase, a key enzyme in nucleotide metabolism, catalyzes the
      hydrolytic deamination of guanine to xanthine. The first guanine deaminase
      crystal from Bacillus subtilis was grown in the absence or presence of the
      inhibitor hypoxanthine in 30% polyethylene glycol 4000, 0.2 M ammonium acetate
      and 0.1 M sodium citrate pH 6.5. The crystals belong to space group C222(1), with
      unit-cell parameters a = 84.91, b = 90.90, c = 80.19 angstroms, with one dimer
      per asymmetric unit. The crystals diffract X-rays to beyond 1.2 angstroms
      resolution and an initial atomic model has been built based on selenomethionyl
      multiwavelength anomalous data at 2 angstroms resolution. Unexpectedly, this is
      the first domain-swapped structure in the cytidine deaminase superfamily.

PMID- 15159587
TI  - Crystallization and preliminary crystallographic analysis of the motor domain of
      human kinetochore-associated protein CENP-E using an automated crystallization
      procedure.
AB  - Human centromere-associated protein E, a member of the kinesin superfamily, is a
      microtubule-dependent motor protein involved in cell division that has been
      localized transiently to the kinetochore. The protein is thought to be
      responsible for the correct attachment and positioning of chromosomes to the
      mitotic spindle during the metaphase. The 312 kDa protein comprises four
      different domains. In this study, the focus was on the N-terminal motor domain,
      which includes the ATP-binding site and a region for microtubule binding.
      Crystals of the CENP-E motor domain have been obtained by high-throughput
      crystallization screening using an automated TECAN crystallization robot. The
      crystals (737 x 132 x 79 microm) belong to the space group P2(1), with unit-cell
      parameters a = 49.35, b = 83.70, c = 94.16 angstroms, beta = 103.05 degrees. They
      diffract to 2.1 angstroms resolution using synchrotron radiation.

PMID- 15159586
TI  - Cloning, expression, purification, crystallization and preliminary
      crystallographic analysis of gamma-filamin repeat 23.
AB  - Human gamma-filamin is a protein of 2705 amino-acid residues that localizes
      mainly in the myofibrillar Z-disc and to smaller extent in the subsarcolemmal
      region of striated muscle cells. gamma-Filamin consists of an N-terminal actin
      binding domain followed by a long rod-shaped region. The rod-shaped region
      consists of 24 immunoglobulin-like domains that form a platform for interaction
      with different transmembrane, cell-signalling and cytoskeletal proteins. gamma
      Filamin repeat 23 was indicated as being necessary for binding to the muscle
      specific subsarcolemmal proteins gamma- and delta-sarcoglycan and the
      myofibrillar protein FATZ1. The recombinant gamma-filamin repeat 23 was
      crystallized using the hanging-drop vapour-diffusion method, which yielded needle
      shaped diffraction-quality crystals. Diffraction data were collected to 2.05
      angstroms resolution using 1.2 angstroms wavelength synchrotron radiation.
      Preliminary structural analysis shows one molecule, with predominantly beta
      secondary-structure elements, per asymmetric unit.

PMID- 15159588
TI  - Crystallization and preliminary crystallographic analysis of the fusion core from
      two new zoonotic paramyxoviruses, Nipah virus and Hendra virus.
AB  - Highly conserved heptad-repeat (HR1 and HR2) regions in class I viral fusion (F)
      proteins, including the F protein from paramyxovirus, interact with each other
      post-fusion to form a six-helix bundle called a fusion core. Crystals of the
      fusion core of Nipah virus have been grown at 291 K using PEG 4000 as
      precipitant. The diffraction pattern of the crystal extends to 2.1 angstroms
      resolution at 100 K in-house. The crystals have unit-cell parameters a = 31.664,
      b = 31.725, c = 51.256 angstroms, alpha = 80.706, beta = 86.343, gamma = 65.812
      degrees and belong to space group P1. Crystals of the fusion core of Hendra virus
      have also been grown at 291 K using PEG 4000 as precipitant. The diffraction
      pattern of the crystal extends to 2.0 angstroms resolution at 100 K in-house. A
      selenomethionine (SeMet) derivative of the HeV fusion core was overexpressed
      using the same Escherichia coli expression system and purified. The derivative
      crystals were obtained under similar conditions and three different wavelength
      data sets were collected to 2.0 angstroms resolution from the derivative crystal
      at BSRF (Beijing Synchrotron Radiation Facility). The crystals have unit-cell
      parameters a = 31.997, b = 31.970, c = 53.865 angstroms, alpha = 85.990, beta =
      85.842, gamma = 68.245 degrees and belong to space group P1.

PMID- 15159589
TI  - Crystallization and preliminary X-ray crystallographic analyses of EcoO109I and
      its complex with DNA.
AB  - EcoO109I is a type II restriction endonuclease that recognizes seven base pairs
      of the degenerate and discontinuous sequence RGGNCCY. The enzyme and its complex
      with DNA were successfully crystallized by the hanging-drop vapour-diffusion
      method using polyethylene glycols as precipitants. The crystal of EcoO109I
      belongs to space group I4, with unit-cell parameters a = b = 175.5, c = 44.6
      angstoms, and that of the DNA complex belongs to space group P2(1)2(1)2(1), with
      unit-cell parameters a = 49.1, b = 71.8, c = 203.2 angstroms. Full sets of X-ray
      diffraction data from the enzyme and its complex with DNA were collected to 2.4
      and 1.9 angstroms resolution, respectively.

PMID- 15159590
TI  - Crystallization and preliminary X-ray analysis of alpha-isopropylmalate synthase
      from Mycobacterium tuberculosis.
AB  - alpha-Isopropylmalate synthase catalyses the aldol condensation of alpha
      ketoisovalerate and acetyl coenzyme A to produce alpha-isopropylmalate. This
      reaction is the first committed step of leucine biosynthesis, which is
      interrelated with the pathways for production of the other branched-chain amino
      acids, valine and isoleucine. The absence of these pathways in mammals suggests
      that these enzymes could be useful targets for drug design against microbial
      pathogens. The gene for alpha-IPMS in Mycobacterium tuberculosis (Rv3710) has
      been cloned, expressed in Escherichia coli, both in native and selenomethionine
      substituted forms, and crystallized. The SeMet crystals are suitable for high
      resolution X-ray structural analysis. These crystals are monoclinic, with unit
      cell parameters a = 54.25, b = 154.73, c = 68.82 angstoms, space group P2(1) and
      two molecules in the asymmetric unit. X-ray diffraction data to 2.0 angstroms
      resolution have been collected.

PMID- 15159591
TI  - Purification and crystallization of the heterodimeric complex of RARbeta and
      RXRalpha ligand-binding domains in the active conformation.
AB  - The ligand-binding domains of the retinoid X receptor alpha (RXRalpha) and of the
      retinoic acid receptor beta (RARbeta) were overexpressed separately and
      copurified in the heterodimeric form. Using a crystallization solution containing
      sodium formate and PEG 3350 as precipitant, the heterodimer was cocrystallized
      with the promiscuous ligand 9-cis-retinoic acid (9C-RA) and a 13-residue fragment
      of the nuclear receptor interaction domain (NID) of the transcriptional
      coactivator TRAP220. The crystals grew in the trigonal space group P3(1)21, with
      unit-cell parameters a = b = 115.7, c = 247.2 angstroms and two heterodimers per
      asymmetric unit. X-ray diffraction data were collected to 2.9 angstroms
      resolution. The structure was solved by molecular replacement and is currently
      being refined.

PMID- 15159592
TI  - Structure of the isoaspartyl peptidase with L-asparaginase activity from
      Escherichia coli.
AB  - The crystal structure of the Escherichia coli enzyme (EcAIII) with isoaspartyl
      dipeptidase and L-asparaginase activity has been solved and refined to a
      resolution of 1.65 angstroms, with crystallographic R-factor and Rfree values of
      0.178 and 0.209, respectively. EcAIII belongs to the family of N-terminal
      hydrolases. The amino-acid sequence of EcAIII is homologous to those of putative
      asparaginases from plants. The structure of EcAIII is similar to the structures
      of glycosylasparaginases. The mature and catalytically active form of EcAIII is a
      heterotetramer consisting of two alpha-subunits and two beta-subunits. Both of
      the equivalent active sites present in the EcAIII tetramer is assisted by a metal
      binding site. The metal cations, modelled here as Na+, have not previously been
      observed in glycosylasparaginases. This reported structure helps to explain the
      inability of EcAIII and other plant-type asparaginases to hydrolyze N4-(beta-N
      acetylglucosaminyl)-L-asparagine, the substrate of glycosylasparaginases.

PMID- 15159593
TI  - Three-dimensional structural characterization of a novel Drosophila melanogaster
      acylphosphatase.
AB  - Analysis of the Drosophila melanogaster EST database led to the discovery and
      cloning of a novel acylphosphatase. The CG18505 gene coding for a new enzyme
      (AcPDro2) is clearly distinct from the previously described CG16870Acyp gene,
      which also codes for a D. melanogaster acylphosphatase (AcPDro). The putative
      catalytic residues, together with residues held to stabilize the acylphosphatase
      fold, are conserved in the two encoded proteins. Crystals of AcPDro2, which
      belong to the trigonal space group P3(1)21, with unit-cell parameters a = b =
      45.8, c = 98.6 angstroms, gamma = 120 degrees, allowed the solution of the
      protein structure by molecular replacement and its refinement to 1.5 angstroms
      resolution. The AcPDro2 active-site structure is discussed.

PMID- 15159594
TI  - The structure of a triple mutant of pI258 arsenate reductase from Staphylococcus
      aureus and its 5-thio-2-nitrobenzoic acid adduct.
AB  - Structural insights into formation of the complex between the ubiquitous thiol
      disulfide oxidoreductase thioredoxin and its oxidized substrate are under
      documented owing to its entropical instability. In vitro, it is possible via a
      reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) to make a stable mixed
      disulfide complex between thioredoxin from Staphylococcus aureus and one of its
      substrates, oxidized pI258 arsenate reductase (ArsC) from S. aureus. In the
      absence of the crystal structure of an ArsC-thioredoxin complex, the structures
      of two precursors of the complex, the ArsC triple mutant ArsC C10SC15AC82S and
      its 5-thio-2-nitrobenzoic acid (TNB) adduct, were determined. The ArsC triple
      mutant has a structure very similar to that of the reduced form of wild-type
      ArsC, with a folded redox helix and a buried catalytic Cys89. In the adduct form,
      the TNB molecule is buried in a hydrophobic pocket and the disulfide bridge
      between TNB and Cys89 is sterically inaccessible to thioredoxin. In order to form
      a mixed disulfide between ArsC and thioredoxin, a change in the orientation of
      the TNB-Cys89 disulfide in the structure is necessary.

PMID- 15159596
TI  - Neonatal outcome in pregnancies after preterm delivery for HELLP syndrome.
AB  - OBJECTIVE: To compare neonatal outcome after preterm delivery of infants where
      pregnancy had been complicated by the HELLP syndrome. STUDY DESIGN: The maternal
      and neonatal charts of 475 consecutive pregnancies complicated by hypertensive
      disorders at our perinatal unit were reviewed. The HELLP syndrome was defined by
      previously published laboratory criteria. 93 women fulfilled the criteria and
      constituted our HELLP syndrome study group. 188 normotensive patients who were
      delivered because of preterm labor comprised the control group. Results were
      compared by means of chi2 analysis and Student's t test where appropriate.
      RESULTS: There were 518 pregnancies complicated by hypertensive disorders and 93
      by HELLP syndrome. The incidence of HELLP syndrome among women with severe
      preeclampsia was 19.5%. We found a significant difference in the incidence of
      intrauterine growth restriction (61.2 vs. 5.8%, p < 0.0001), intrauterine fetal
      death (13.9 vs. 6.9%, p = 0.035), abruptio placenta (13.9 vs. 2.6%, p = 0.001),
      and fetal distress (35.4 vs. 12.2%, p < 0.0001) between the two groups. There
      were no significant differences in complications (respiratory distress syndrome,
      intraventricular hemorrhage, necrotizing enterocolitis and sepsis) between the
      HELLP syndrome group and controls. However, the neonatal death rate and the need
      for mechanical ventilation and neonatal intensive care were greater in the HELLP
      syndrome group. CONCLUSIONS: Our study suggests an increased mortality and
      morbidity in newborns of mothers complicated with HELLP syndrome that can be
      partly attributed to increased rates of intrauterine growth restriction and fetal
      distress, particularly beyond 32 weeks of gestation.

PMID- 15159597
TI  - Brain plasticity in multiple sclerosis.

PMID- 15159598
TI  - Normal brain activation in hemiatrophy due to multiple sclerosis: a functional
      MRI case study.
AB  - Evidence from recent functional magnetic resonance imaging studies suggests that
      adaptive cortical changes ('plasticity') could participate in the maintenance of
      function in multiple sclerosis (MS). Here, we addressed the impact of brain
      atrophy on the pattern of cerebral activation in an MS patient with a relapsing
      remitting course. This patient showed mildly disabling hemiparesis of the left
      side (EDSS 2.0), and corresponding brain hemiatrophy (15% volume reduction) of
      the right hemisphere. The clinical syndrome was considered to result from a
      lesion in the corona radiata involving corticospinal fibers. Motor-evoked
      potential recordings confirmed substantial axonal damage to the pyramidal tract
      arising from that hemisphere. Irrespective of these asymmetries, normal brain
      activation was found for hand and foot movements for both brain sides. This
      demonstrates that brain atrophy itself does not necessarily induce cortical
      adaptive changes, even if mild disability is present. On the other hand,
      significantly disabling distinct clinical syndromes e.g. arising from spinal cord
      lesions may evoke cortical changes irrespective of brain atrophy. This issue has
      to be studied in longitudinal investigations.

PMID- 15159599
TI  - Sensory nerve conduction in demyelinating and axonal Guillain-Barre syndromes.
AB  - Guillain-Barre syndrome is divided into acute inflammatory demyelinating
      polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) based on motor
      nerve conduction studies. We investigated whether sensory nerve conduction
      studies contribute to the electrodiagnosis of AIDP and AMAN. In consecutive 59
      patients with AIDP (n = 26) or AMAN (n = 33), results of sensory nerve conduction
      studies in the median, ulnar and sural nerves were reviewed. Sensory nerve
      conduction abnormalities were found for 85% of AIDP patients and for only 6% of
      AMAN patients. In AIDP patients, the abnormalities were present in 85% of
      patients in the median nerves, 85% in the ulnar nerves and 38% in the sural
      nerves. AMAN is very rarely associated with sensory nerve involvement. Abnormal
      sensory nerve conduction is supportive of AIDP and is more frequently found for
      the median and ulnar nerves than sural nerves.

PMID- 15159600
TI  - Preclinical memory profile in Alzheimer patients with and without allele APOE
      epsilon4.
AB  - To investigate the association between APOE-epsilon4 allele and memory phenotype
      in the preclinical stage of Alzheimer's disease (AD). We compared an extensive
      preclinical memory profile at the baseline evaluation of 2 AD genotype groups:
      APOE-epsilon4 allele carriers and patients with APOE-epsilon3 homozygosity.
      Baseline memory performance was carried out at least 2 years (interval of 27.7 +/
      4 months) before AD diagnosis was established, and analysis included different
      modalities of working memory (visuoperceptive, visuospatial, digit span and
      processing speed), of declarative memory (recent, verbal learning, prospective
      and semantic) and of nondeclarative memory (procedural, incidental and priming).
      We found no significant differences: memory performance was similar in both
      genotype groups. The presence of the APOE-epsilon4 allele does not seem to be
      sufficient to cause a distinctive preclinical memory phenotype in AD patients.

PMID- 15159602
TI  - Apolipoprotein E and alpha-1-antichymotrypsin polymorphisms in sporadic inclusion
      body myositis.
AB  - Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of
      unknown aetiology. Characteristically, intracellular amyloid deposits are
      detectable, including beta-amyloid precursor protein, phosphorylated tau, alpha1
      antichymotrypsin (alpha1-ACT) and apolipoprotein E (ApoE). Polymorphisms and
      mutations of the encoding genes have been identified in a variety of
      neurodegenerative diseases including Alzheimer's disease (AD). Beside other
      factors, polymorphisms may lead to protein accumulation in both diseases. In
      particular, polymorphisms within the ApoE and alpha1-ACT gene have been
      implicated in the aetiology of AD and s-IBM. We analysed ApoE and alpha1-ACT gene
      polymorphisms in 35 s-IBM patients. We could not identify any statistical
      significant correlation between distinct ApoE and alpha1-ACT genotypes and the
      risk of developing s-IBM. Additionally, ApoE and alpha1-ACT genotypes seem not to
      influence the onset age of s-IBM. A combination of different alpha1-ACT and ApoE
      genotypes appears not to enhance the risk of developing s-IBM. Therefore, allelic
      variations of alpha1-ACT and ApoE are unlikely to be genetic key factors in the
      aetiology of s-IBM.

PMID- 15159601
TI  - Congenital insensitivity to pain with anhidrosis in Taiwan: a morphometric and
      genetic study.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by
      insensitivity to pain, anhidrosis, recurrent hyperpyrexia, mild mental
      retardation, and self-mutilating behavior. We report 2 brothers, aged 20 and 18
      years, who suffered from phenotypes of CIPA. Both brothers had a branch site
      mutation in intron 7 (IVS7-33 T-->A) of the neurotrophic tyrosine kinase receptor
      type 1 gene. The electrophysiological studies showed no significant abnormal
      findings in sensory evoked potentials, motor evoked potentials to transcranial
      magnetic stimulation, or heart rate variations; sympathetic skin responses were
      absent. Morphometric study of their sural nerve histopathology revealed normal
      myelinated fiber density, 8,082 fibers/mm2 and 5,637 fibers/mm2 (normal 6,141 +/-
      421); decreased unmyelinated fiber density, 2,537 fibers/mm2 and 2,211 fibers/mm2
      (normal 28,578 +/- 8,669); increased axon size, 4.41 +/- 1.59 microm and 5.33 +/-
      1.48 microm (normal 3.73 +/- 1.45), and increased axon diameter (A)/myelin
      thickness (M) ratio (A/M), 3.47 +/- 1.42 and 2.70 +/- 1.07 (normal 2.49 +/-
      0.93). Scatterplot analysis of the G ratio (axon diameter:fiber diameter) did not
      show consistent results in the relationship between axon size and myelin
      thickness. In conclusion, the neuropathy of our CIPA patients included a marked
      reduction of small myelinated and unmyelinated fibers and a relatively increased
      axon size. This is the first CIPA family encountered in Taiwan.

PMID- 15159603
TI  - Cardiac cephalalgia. Case report and review of the literature with new ICHD-II
      criteria revisited.
AB  - We report a patient with cardiac cephalalgia and review reported cases from the
      English-language literature based on the new diagnostic criteria published in the
      International Classification of Headache Disorders, ed 2. Twenty-two patients,
      including ours, with headaches of cardiac origin were reviewed. The cases fit
      three of the four new criteria well: Criteria B (acute myocardial ischemia has
      occurred, 100%), C (headache developed concomitantly with acute myocardial
      ischemia, 100%), and D (headache resolved and does not recur after effective
      medical or surgical treatment for myocardial ischemia, 83%). The cases in which
      we had exceptions were to the proposed headache features (criterion A), which
      were generally not fulfilled, with nausea as the least frequent finding (27%);
      this criterion might not be mandatory for diagnosis.

PMID- 15159604
TI  - Generalized chorea associated with bilateral chronic subdural hematoma.
AB  - A variety of acquired disorders cause chorea, such as hypoxia-ischemia injury,
      drugs, toxins, infections, autoimmune disorders, and endocrine and electrolyte
      abnormalities, but rarely subdural hematoma. We report the case of a 76-year-old
      woman who presented with sudden onset of generalized choreiform movements 1 day
      prior to admission. Computed tomography revealed a bilateral lateral convexity
      subdural effusion, which was later confirmed by magnetic resonance imaging as a
      chronic subdural hematoma. After surgical evacuation of the subdural hematoma,
      the choreoathetoid movements ceased completely. We propose that transient
      ischemia in the bilateral subcortical regions was from compression and distortion
      of the brain by the bilateral hematomas and resulted in generalized chorea.

PMID- 15159605
TI  - Paraneoplastic sensorimotor neuropathy and encephalopathy associated with anti
      alpha-enolase antibody in a case of gastric adenocarcinoma.

PMID- 15159606
TI  - Bilateral anterior inferior cerebellar artery territory brachium pontis infarcts
      of probable hemodynamic cause.

PMID- 15159607
TI  - Acute bilateral medial medullary infarction: a unique 'heart appearance' sign by
      diffusion-weighted imaging.

PMID- 15159608
TI  - Inflammatory pseudotumor of temporal bone with pachymeningitis, cranial
      neuropathies and uveitis.

PMID- 15159609
TI  - Olfactory illusions and hallucinations after right temporal hemorrhage.

PMID- 15159610
TI  - Paradoxical focal hyperhidrosis in response to cold after faulty regeneration.

PMID- 15159611
TI  - Successful pharmacotherapy for an adult case with prolonged symptoms of
      postganglionic cholinergic dysautonomia.

PMID- 15159612
TI  - Sodium bromide encephalopathy with decreased serum Cl- level and increased anion
      gap: report of one case.

PMID- 15159614
TI  - Midbrain ischemia presenting as vertical gaze palsy: value of diffusion-weighted
      magnetic resonance imaging.
AB  - BACKGROUND: Conventional magnetic resonance imaging may fail to identify very
      small but clinically relevant acute subcortical brain infarcts. Diffusion
      weighted magnetic resonance imaging (DWI) is very sensitive and specific for
      acute cerebral ischemia and should contribute to the early detection of such
      lesions. METHODS: We analyzed 6 patients who presented with acute vertical gaze
      palsy and in whom DWI was performed within 1-6 days from symptom onset. RESULTS:
      DWI accurately identified ischemia in an area supplied by the posterior
      thalamosubthalamic paramedian artery in all patients. T(2)-weighted and FLAIR
      imaging failed to identify the clinically relevant lesion in 2 and 3 patients,
      respectively. CONCLUSION: DWI improves the clinicoanatomical correlation in
      patients presenting with supranuclear oculomotor disturbances.

PMID- 15159613
TI  - Statins for secondary stroke prevention in patients without known coronary heart
      disease: the jury is still out.

PMID- 15159615
TI  - Direct medical costs attributable to acute myocardial infarction and ischemic
      stroke in cohorts with atherosclerotic conditions.
AB  - BACKGROUND: The cost of acute ischemic events in persons with established
      atherosclerotic conditions is unknown. METHODS: The direct medical costs
      attributable to secondary acute myocardial infarction (AMI) or ischemic stroke
      among persons with established atherosclerotic conditions were estimated from
      1995-1998 data on 1,143 patients enrolled in US managed care plans. RESULTS: The
      average 180-day costs attributable to secondary AMI or stroke were estimated as
      USD 19,056 in the AMI cohort having a private insurance (commercial; n = 344),
      USD 16,845 in the AMI cohort having government insurance (Medicare, age >/=65
      years; n = 200), USD 10,267 for stroke commercial (n = 108), USD 16,280 for
      stroke Medicare (n = 113), USD 15,224 for peripheral arterial disease commercial
      (n = 170), and USD 15,182 for peripheral arterial disease Medicare (n = 208).
      CONCLUSION: These estimates can be used to study the cost-effectiveness of
      interventions proven to reduce these secondary events.

PMID- 15159616
TI  - Mishaps in the management of stroke: a review of 214 complaints to a medical
      responsibility board.
AB  - BACKGROUND: This is the first survey of formal complaints to a Medical
      Responsibility Board (MRB) in the literature concerning stroke management and the
      disciplinary actions to which the complaints lead. METHODS: All available
      complaints submitted to the Swedish MRB during a 5-year period that concerned
      stroke management (n = 214) were reviewed. We compiled information on the
      plaintiffs, the health care staff the complaints were directed against, the area
      of stroke management involved and the disciplinary actions taken by the MRB.
      RESULTS: Only 1% of all complaints to the MRB concerned stroke. Three quarters of
      these complaints were directed against physicians and one fifth against nurses.
      23 complaints (11%) resulted in a warning or an admonition. Nearly all
      disciplinary actions against physicians (12 of 13) concerned misdiagnoses, of
      subarachnoid hemorrhage in particular. The most common reason for a nurse
      receiving a warning or an admonition was negligent handling of drugs.
      CONCLUSIONS: The survey has identified two areas in which educational programs to
      improve patient safety seem essential. The small number of formal complaints and
      disciplinary actions suggest that other, blameless procedures have a greater
      potential than MRB actions to reduce mishaps in routine stroke care.

PMID- 15159617
TI  - Long-term change in size of cerebral infarction: predictive value of brain
      perfusion SPECT using statistical parametric mapping.
AB  - A focus of infarction is surrounded by hypoperfused areas. The present study was
      undertaken to examine the long-term changes in the size of infarcts, the
      relationship between the size of an infarct and the extent of the surrounding
      hypoperfused areas, and the background of such changes. The subjects of this
      study were 11 patients with ischemic lesions of the brain who had undergone brain
      SPECT ((99m)Tc-ethyl cysteinate dimer) within 1 week after initial MRI, and who
      underwent MRI again more than half a year later. Statistical parametric mapping
      (SPM) was conducted to detect significantly hypoperfused areas on the SPECT
      images. Relative size of significantly hypoperfused areas on SPM and infarcts on
      T(2)-weighted MR images were measured. The patients were divided into two groups
      based on the percentage of the infarct's size relative to the size of the
      surrounding hypoperfused areas (75-125 and 0-39%). Infarcts in the '75-125%'
      group showed little change in size, while in the '0-39%' group infarcts increased
      slowly until it reached the same rate as the former group. All patients with
      infarct in the '0-39%' group were noted to have severe stenosis of the internal
      carotid arteries bilaterally. Patients having severe stenosis of the internal
      carotid artery often had a slowly enlarging infarct. SPM seems to be useful in
      predicting the ultimate size of the infarct.

PMID- 15159618
TI  - Pulse pressure in acute stroke is an independent predictor of long-term
      mortality.
AB  - The management of blood pressure (BP) during the acute phase of stroke remains a
      matter of debate. The aim of the present study was to evaluate a possible
      association between long-term mortality and BP values in acute stroke by means of
      BP monitoring. We studied a consecutive series of 198 first-ever acute stroke
      patients. BP monitoring was initiated in all subjects within 24 h of ictus. One
      year after stroke onset, 34 (17.7%) patients had died. Multivariate Cox
      regression analysis revealed only age, level of consciousness on admission,
      lacunar stroke and 24-hour pulse pressure (24-hour PP) as significant outcome
      predictors. The hazards ratio for 1-year mortality associated with every 10 mm Hg
      increase in 24 h PP was 1.39 (95% CI: 1.04-1.86, p = 0.028). The present results
      demonstrate that increasing 24-hour PP levels in patients with acute stroke are
      independently associated with higher long-term mortality. This may have
      implications in acute stroke BP management and warrants further investigation.

PMID- 15159619
TI  - Time trends in the published risks of stroke and death due to endarterectomy for
      symptomatic carotid stenosis.
AB  - BACKGROUND: Large randomised trials performed in the 1980s and early 1990s showed
      that carotid endarterectomy (CEA) is beneficial for patients with recently
      symptomatic severe stenosis. Some surgeons have argued that the operative risk of
      stroke and death has fallen over the last decade due to refinements in operative
      technique, and that the indications for surgery should therefore now be
      broadened. Yet, studies of routinely collected data report higher operative
      mortality than in the trials, and surgical case series without independent post
      operative assessment by a neurologist may not provide reliable data on stroke
      risk. METHODS: We performed a systematic review of all studies published between
      1994 and 2001 inclusive that which reported the risks of stroke and death for
      symptomatic carotid stenosis, and compared the reported risks and patient
      characteristics with those in the ECST and NASCET and with our previous review of
      studies published prior to 1995. Pooled estimates of the operative risk of stroke
      and death were obtained by Mantel-Haenszel meta-analysis. RESULTS: Of 383 studies
      published between 1994 and 2001, only 45 reported operative risks for patients
      with symptomatic stenosis separately. The pooled operative risk of stroke and
      death reported in studies published by surgeons only (4.2%, 95% CI = 2.9-5.5, 34
      studies) was significantly lower (p < 0.0001) than that in the ECST and NASCET
      combined (7.0%, 95% CI = 6.2-8.0), whereas the pooled risk reported in studies
      that involved neurologists was similar (6.5%, 95% CI = 4.3-8.7, 11 studies, p =
      0.6). In contrast, operative mortality in ECST and NASCET was significantly lower
      than in other studies published between 1994 and 2001. By comparison with our
      previous review, when stratified according to involvement of neurologists, we
      found no evidence of a reduction in published risks of death or stroke and death
      due to CEA between 1985 and 2001. CONCLUSIONS: There is no evidence of a
      systematic reduction over the last decade in the published risks of stroke and
      death due to CEA for symptomatic stenosis. Operative risks in studies with
      comparable outcome assessment are similar to ECST and NASCET. The surgical data
      from the large trials are still likely therefore to be applicable to routine
      clinical practice.

PMID- 15159621
TI  - The wound-inducible Lls1 gene from maize is an orthologue of the Arabidopsis Acd1
      gene, and the LLS1 protein is present in non-photosynthetic tissues.
AB  - Previous studies indicated that the lethal leaf spot 1 lesion mimic locus of
      maize ( ZmLls1 ) encodes a novel cell protective function in plants. Here we show
      that the accelerated cell death 1 ( acd1 ) locus of Arabidopsis thaliana
      corresponds to gene At3g44880 on chromosome 3. Proof that the Acd1 gene is an
      orthologue of ZmLls1 is provided by in vivo complementation of the acd1 mutant by
      the ZmLls1 gene. The Atlls1 lesion mimic phenotype was delayed in a chlorophyll a
      oxygenase (CAO) mutant chlorina1 background which is deficient in chlorophyll b
      synthesis. The interpretation that the cell protective function of LLS1 is linked
      with the removal of a phototoxic chlorophyll intermediate is supported by the
      recent report that the maize Lls1 gene encodes pheophorbide a oxygenase (PaO).
      Western blot analysis demonstrates that the LLS1 protein is present
      constitutively in all photosynthetic plant tissues. A transient increase in Lls1
      gene expression by about 50-fold upon physical wounding of maize leaves indicates
      that the function of Lls1 is regulated in response to stress. We show that the
      LLS1 protein is also present at low levels in non-photosynthetic tissues
      including etiolated leaves suggesting that the ability to degrade chlorophyll
      exists in a standby mode in plant cells.

PMID- 15159623
TI  - Proteomic analysis of glutathione S -transferases of Arabidopsis thaliana reveals
      differential salicylic acid-induced expression of the plant-specific phi and tau
      classes.
AB  - Plant glutathione S -transferases (GSTs) are a large group of multifunctional
      proteins that are induced by diverse stimuli. Using proteomic approaches we
      identified 20 GSTs at the protein level in Arabidopsis cell culture with a
      combination of GST antibody detection, LC-MS/MS analysis of 23-30 kDa proteins
      and glutathione-affinity chromatography. GSTs identified were from phi, tau,
      theta, zeta and DHAR sub-sections of the GST superfamily of 53 members. We have
      uncovered preliminary evidence for post-translational modifications of plant GSTs
      and show that phosphorylation is unlikely to be responsible. Detailed analysis of
      GST expression in response to treatment with 0.01-1 mM of the plant defence
      signal salicylic acid (SA) uncovered some interesting features. Firstly, GSTs
      appear to display class-specific concentration-dependent SA induction profiles
      highlighting differences between the large, plant specific phi and tau classes.
      Secondly, different members of the same class, while sharing similar SA dose
      responses, may display differences in terms of magnitude and timing of induction,
      further highlighting the breadth of GST gene regulation. Thirdly, closely related
      members of the same class ( GSTF6 and GSTF7 ), arising via tandem duplication,
      may be regulated differently in terms of basal expression levels and also
      magnitude of induction raising questions about the role of subfunctionalisation
      within this family. Our results reveal that GSTs exhibit class specific responses
      to SA treatment suggesting that several mechanisms are acting to induce GSTs upon
      SA treatment and hinting at class-specific functions for this large and
      important, yet still relatively elusive gene family.

PMID- 15159622
TI  - Identification of signals required for import of the soybean F(A)d subunit of ATP
      synthase into mitochondria.
AB  - The requirements for protein import into mitochondria was investigated by using
      the targeting signal of the F(A)d subunit of soybean mitochondrial ATP synthase
      attached to two different passenger proteins, its native passenger and soybean
      alternative oxidase. Both passenger proteins are soybean mitochondrial proteins.
      Changing hydrophobic residues at positions -24:25 (Phe:Leu), -18:19 (Ile:Leu) and
      -12:13 (Leu:Ile) of the 31 amino acid cleavable presequence gave more than 50%
      inhibition of import with both passenger proteins. Some other residues in the
      targeting signal played a more significant role in targeting of one passenger
      protein compared to another. Notably changing positive residues (Arg, Lys) had a
      greater inhibitory affect on import with the native passenger protein, i.e.
      greater inhibition of import with F(A)d mature protein was observed compared to
      when alternative oxidase was the mature protein. When using chimeric passenger
      proteins it was shown that the nature of the mature protein can greatly affect
      the targeting properties of the presequence. In vivo investigations of the
      targeting presequence indicated that the presequence of 31 amino acids could not
      support import of GFP as a passenger protein. However, fusion of the full-length
      F(A)d coding sequence to GFP did result in mitochondrial localisation of GFP.
      Using the latter fusion we confirmed the critical role of hydrophobic residues at
      positions -24:25 and -18:19. These results support the proposal that core
      mitochondrial targeting features exist in all presequences, but that additional
      features exist. These features may not be evident with all passenger proteins.

PMID- 15159620
TI  - Characteristics of RNA silencing in plants: similarities and differences across
      kingdoms.
AB  - RNA silencing is a collective term that encompasses the sequence of events that
      leads to the targeted degradation of cellular mRNA and thus to the silencing of
      corresponding gene expression. RNA silencing is initiated after introduction into
      the host genome of a gene that is homologous to an endogenous gene. Transcription
      of the introduced gene results in the formation of double-stranded RNA (dsRNA)
      that is cut into smaller dsRNA species termed small interfering RNAs (siRNAs) by
      an RNaseIII-like enzyme called 'Dicer'. siRNAs associate with a protein complex
      termed the 'RNA-induced silencing complex' (RISC), which mediates the binding of
      one strand of siRNAs with mRNAs transcribed from the native 'target' gene. The
      binding of siRNAs with native gene mRNAs earmarks native gene mRNAs for
      destruction, resulting in gene silencing. In plants, RNA silencing appears to
      serve as a defence mechanism against viral pathogens and also to suppress the
      activity of virus-like mobile genetic elements. In an apparent response to RNA
      silencing, some plant viruses express suppressors of RNA silencing. RNA silencing
      also is directly implicated in the regulation of the function(s) of microRNAs,
      which are the key determinants in an additional cellular mechanism related to the
      translational repression of genes, the effect of which ultimately impinges on
      development. The high degree of sequence similarity that exists between genes
      involved in RNA silencing in widely different organisms underscores the conserved
      nature of many aspects of the RNA silencing mechanism. However, depending (for
      example) on the precise nature of the target gene involved, there also are
      significant differences in the silencing pathways that are engaged by various
      organisms.

PMID- 15159624
TI  - Characterization of the brassinosteroid insensitive 1 genes of cotton.
AB  - Suppression of brassinosteroid (BR) biosynthesis in cotton ovules by treatment
      with brassinazole inhibits fiber formation, indicating that BR plays an important
      role in cotton fiber development. Plant responses to brassinosteroids (BR) are
      mediated through a plasma membrane-bound leucine-rich repeat (LRR) receptor-like
      protein kinase known as BRI1. Mutations in the BRI1 genes of several species
      result in dwarfed plants with reduced sensitivity to BR. A single expressed
      sequence tag (EST) from cotton with strong sequence similarity to Arabidopsis
      BRI1 ( AtBRI1 ) was identified in a search of publicly available databases. With
      this EST as a starting point, full-length cDNAs and genomic coding sequences from
      upland cotton ( Gossypium hirsutum ) BRI1 ( GhBRI1 ) were obtained and
      characterized. Ectopic expression of this coding sequence in BR-insensitive
      Arabidopsis plants resulted in recovery of normal growth indicating that GhBRI1
      is a functional homologue of AtBRI1. G. hirsutum is an allotetraploid (AADD)
      derived from diploid ancestors. Analysis of several GhBRI1 cDNAs showed two
      distinct sequences indicating the presence of two GhBRI1 genes, denoted GhBRI1-1
      and GhBRI1-2. Sequence comparisons between these GhBRI1 coding sequences and
      those from related A and D genome diploid Gossypium species ( G. arboreum and G.
      thurberi ) indicated that GhBRI1-1 is likely to the A sub-genome orthologue while
      GhBRI1-2 is from the D sub-genome.

PMID- 15159625
TI  - Arabidopsis Acyl-CoA-binding protein ACBP2 interacts with an ethylene-responsive
      element-binding protein, AtEBP, via its ankyrin repeats.
AB  - Cytosolic acyl-CoA-binding proteins (ACBP) bind long-chain acyl-CoAs and act as
      intracellular acyl-CoA transporters and maintain acyl-CoA pools. Arabidopsis
      thaliana ACBP2 shows conservation at the acyl-CoA-binding domain to cytosolic
      ACBPs but is distinct by the presence of an N-terminal transmembrane domain and C
      terminal ankyrin repeats. The function of the acyl-CoA-binding domain in ACBP2
      has been confirmed by site-directed mutagenesis and four conserved residues
      crucial for palmitoyl-CoA binding have been identified. Results from ACBP2:GFP
      fusions transiently expressed in onion epidermal cells have demonstrated that the
      transmembrane domain functions in plasma membrane targeting, suggesting that
      ACBP2 transfers acyl-CoA esters to this membrane. In this study, we investigated
      the significance of its ankyrin repeats in mediating protein-protein interactions
      by yeast two-hybrid analysis and in vitro protein-binding assays; we showed that
      ACBP2 interacts with the A. thaliana ethylene-responsive element-binding protein
      AtEBP via its ankyrin repeats. This interaction was lacking in yeast two-hybrid
      analysis upon removal of the ankyrin repeats. When the subcellular localizations
      of ACBP2 and AtEBP were further investigated using autofluorescent protein
      fusions in transient expression by agroinfiltration of tobacco leaves, the
      DsRed:ACBP2 fusion protein was localized to the plasma membrane while the
      GFP:AtEBP fusion protein was targeted to the nucleus and plasma membrane. Co
      expression of DsRed:ACBP2 and GFP:AtEBP showed a common localization of both
      proteins at the plasma membrane, suggesting that ACBP2 likely interacts with
      AtEBP at the plasma membrane.

PMID- 15159626
TI  - Transgenic rice plants expressing the antifungal AFP protein from Aspergillus
      giganteus show enhanced resistance to the rice blast fungus Magnaporthe grisea.
AB  - The Aspergillus giganteus antifungal protein (AFP), encoded by the afp gene, has
      been reported to possess in vitro antifungal activity against various
      economically important fungal pathogens, including the rice blast fungus
      Magnaporthe grisea. In this study, transgenic rice ( Oryza sativa )
      constitutively expressing the afp gene was generated by Agrobacterium -mediated
      transformation. Two different DNA constructs containing either the afp cDNA
      sequence from Aspergillus or a chemically synthesized codon-optimized afp gene
      were introduced into rice plants. In both cases, the DNA region encoding the
      signal sequence from the tobacco AP24 gene was N-terminally fused to the coding
      sequence of the mature AFP protein. Transgenic rice plants showed stable
      integration and inheritance of the transgene. No effect on plant morphology was
      observed in the afp -expressing rice lines. The inhibitory activity of protein
      extracts prepared from leaves of afp plants on the in vitro growth of M. grisea
      indicated that the AFP protein produced by the trangenic rice plants was
      biologically active. Several of the T(2) homozygous afp lines were challenged
      with M. grisea in a detached leaf infection assay. Transformants exhibited
      resistance to rice blast at various levels. Altogether, the results presented
      here indicate that AFP can be functionally expressed in rice plants for
      protection against the rice blast fungus M. grisea.

PMID- 15159627
TI  - Two rice GRAS family genes responsive to N -acetylchitooligosaccharide elicitor
      are induced by phytoactive gibberellins: evidence for cross-talk between elicitor
      and gibberellin signaling in rice cells.
AB  - In this study, we present data showing that two members of the GRAS family of
      genes from rice, CIGR1 and CIGR2 (chitin-inducible gibberellin-responsive),
      inducible by the potent elicitor N -acetylchitooligosaccharide (GN), are rapidly
      induced by exogenous gibberellins. The pattern of mRNA accumulation was dependent
      on the dose and biological activity of the gibberellins, suggesting that the
      induction of the genes by gibberellin is mediated by a biological receptor
      capable of specific recognition and signal transduction upon perception of the
      phytoactive compounds. Further pharmacological analysis revealed that the CIGR1
      and CIGR2 mRNA accumulation by treatment with gibberellin is dependent upon
      protein phosphorylation/dephosphorylation events. In rice calli derived from
      slender rice 1, a constitutive gibberellin-responsive mutant, or d1, a mutant
      deficient in the alpha -subunit of the heterotrimeric G-protein, CIGR1 and CIGR2
      were induced by a GN elicitor, yet not by gibberellin. Neither gibberellin nor GN
      showed related activities in defense or development, respectively. These results
      strongly suggested that the signal transduction cascade from gibberellin is
      independent of that from GN, and further implied that CIGR1 and CIGR2 have dual,
      distinct roles in defense and development.

PMID- 15159628
TI  - Developmental and cell-specific expression of ZWICHEL is regulated by the intron
      and exon sequences of its gene.
AB  - Functional studies with ZWICHEL ( ZWI ), which encodes a Ca(2+)-calmodulin
      regulated kinesin, have shown its involvement in trichome morphogenesis and cell
      division. To identify regulatory regions that control the ZWI expression pattern,
      we generated transgenic Arabidopsis plants with a GUS reporter driven by
      different lengths of the ZWI gene 5' region alone or 5' and 3' regions together.
      The 5' fusions contain varying lengths of the coding and non-coding regions of
      beta - HYDROXYISOBUTYRYL-CoA HYDROLASE 1 ( CHY1 ), which is upstream of ZWI, and
      a 162 bp intergenic region. In transgenic plants with 5' 460::GUS, GUS activity
      was observed primarily in the root hairs whereas transgenic plants with an
      additional 5' 266 bp region from the CHY1 gene (5' 726::GUS) showed strong GUS
      accumulation in the entire root including root hairs and root tip, calli and at
      various developmental stages in trichomes and pollen. However, very little GUS
      accumulation was detected in roots of dark-grown or root tips of cold-treated
      seedlings with 5' ZWI constructs. These results were further confirmed by
      quantifying GUS enzyme activity and transcripts in these seedlings. Calli and
      pollen transformed with the 5' distal 268 bp fused in antisense orientation to
      the proximal 460 bp did not show GUS expression. Further, IAA-treated dark-grown
      seedlings with 726::GUS, but not with 460::GUS, showed high GUS expression in
      specific regions (outer layer 2a cells) at the base of the lateral roots. The ZWI
      3' region (3 kb) did not influence the GUS expression pattern driven by the 5'
      726 bp. The absence of CHY1 transcripts in the chy1-2 mutant did not alter either
      ZWI expression or ZWI-mediated trichome morphogenesis. Thus, our data suggest
      that the 3' part of the CHY1 gene contains regulatory elements that control ZWI
      gene expression in dividing cells and other cells that exhibit polarized growth
      such as root hairs, pollen and trichomes. This is the first evidence that the
      regulatory regions conferring developmental and cell-specific expression of a
      gene reside in the introns and exons of its upstream protein-coding gene.

PMID- 15159630
TI  - A novel zinc-finger protein with a proline-rich domain mediates ABA-regulated
      seed dormancy in Arabidopsis.
AB  - Seed dormancy is an important developmental process that prevents pre-harvest
      sprouting in many grains and other seeds. Abscisic acid (ABA), a plant hormone,
      plays a crucial role in regulating dormancy but the underlying molecular
      regulatory mechanisms are not fully understood. An Arabidopsis zinc-finger gene,
      MEDIATOR OF ABA-REGULATED DORMANCY 1 ( MARD1 ) was identified and functionally
      analyzed. MARD1 expression is up-regulated by ABA. A T-DNA insertion in the
      promoter region downstream of two ABA-responsive elements (ABREs) renders MARD1
      unable to respond to ABA. The mard1 seeds are less dormant and germinate in total
      darkness; their germination is resistant to external ABA at the stage of radicle
      protrusion. These results suggest that this novel zinc-finger protein with a
      proline-rich N-terminus is an important downstream component of the ABA signaling
      pathway that mediates ABA-regulated seed dormancy in Arabidopsis.

PMID- 15159631
TI  - In vitro reconstitution of rice anthranilate synthase: distinct functional
      properties of the alpha subunits OASA1 and OASA2.
AB  - Anthranilate synthase (AS) is a key enzyme in the biosynthesis of various indole
      compounds including tryptophan. AS consists of two subunits, alpha and beta, and
      converts chorismate to anthranilate. Two or more AS alpha-subunit genes have been
      identified and characterized in several land plants. Although alpha subunits of
      AS induced by elicitation have been suggested to play significant roles in
      secondary metabolism, the biochemical and precise functional properties of
      individual AS isozymes have remained unclear. We have previously identified and
      characterized two AS alpha-subunit genes (OASA1 and OASA2) in rice (Oryza sativa
      ). To provide further insight into the enzymatic functions of AS isozymes in
      rice, we have now isolated rice cDNAs encoding the AS beta subunits OASB1 and
      OASB2 and reconstituted AS isozymes in vitro with the wheat germ cell-free system
      for protein expression. Both OASB subunits conferred glutamine-dependent AS
      activity on either OASA1 or OASA2, indicating the absence of a marked functional
      difference between the two beta subunits in terms of amidotransferase activity.
      Furthermore, both OASA subunits required assembly with a beta subunit to achieve
      maximal enzymatic activity even with NH(4)(+) as the amino donor. The V (max) and
      K (i) for tryptophan of the OASA1-OASB1 isozyme with glutamine as the amino
      donor, however, were 2.4 and 7.5 times, respectively, those of OASA2-OASB1,
      suggesting that AS isozymes containing OASA1 possess a higher activity and are
      less sensitive to feedback inhibition than those containing OASA2. Our
      biochemical characterization of reconstituted AS isozymes has thus revealed
      distinct functional properties of these isozymes in rice.

PMID- 15159629
TI  - OsPIPK 1, a rice phosphatidylinositol monophosphate kinase, regulates rice
      heading by modifying the expression of floral induction genes.
AB  - A rice gene, OsPIPK 1, encoding a 792-aa putative phosphatidylinositol 4
      phosphate 5-kinase (PIPK), was identified and characterized. Comparison between
      the cDNA and genomic sequences revealed the presence of 10 exons (39-1050 bp) and
      9 introns (88-745 bp) in OsPIPK 1 gene. The deduced amino acid sequence of
      OsPIPK1 contains a lipid kinase domain that is highly homologous to those of
      previously isolated PIPKs, and structural analysis revealed the intriguing
      presence of multiple MORN motifs at the N-terminus. The MORN motifs have also
      been detected in PIPKs from Arabidopsis thaliana and Oryza sativa, but not in the
      well-characterized PIPKs from animal and yeast cells. RT-PCR analysis indicated
      that OsPIPK 1 was expressed almost constitutively in roots, shoots, stems, leaves
      and flowers, and up-regulated following treatment with plant hormones or
      application of various stresses. An antisense transgenic strategy was used to
      suppress the expression of OsPIPK 1, and homozygous transgenic plants showed
      earlier heading (7-14 days earlier) than control plants, suggesting that OsPIPK 1
      negatively regulates floral initiation. This was further confirmed by morphologic
      observation showing earlier floral development in antisense plants, as well as
      leaf emergence measurement indicating delayed leaf development under OsPIPK 1
      deficiency, a common phenotype observed with earlier flowering. RT-PCR analysis
      and cDNA chip technology were used to examine transcripts of various genes in the
      transgenic plants and the results showed altered transcriptions of several
      flowering-time or -identity related genes, suggesting that OsPIPK 1 is involved
      in rice heading through regulation of floral induction genes, signaling and
      metabolic pathways.

PMID- 15159632
TI  - The 5' UTR negatively regulates quantitative and spatial expression from the ABI3
      promoter.
AB  - The involvement of transcription factors Arabidopsis abscisic acid-insensitive3
      (ABI3), maize viviparous1 (VP1) and Phaseolus vulgaris ABI3-like factor (PvALF)
      in the spatial control of storage protein gene expression is well established.
      However, little insight exists as to how they are themselves regulated. To
      address this, a 5.15 kb ABI3 upstream sequence including a 4.6 kb full-length
      promoter and 519 bp of 5'-untranslated region (UTR) was used to drive either beta
      glucuronidase (GUS) or green fluorescent protein (GFP) expression in Arabidopsis.
      Expression from the full-length (- 4630/ + 519ABI3 ) and various 5'-truncated
      promoters was detected during embryogenesis in all lines, except those transgenic
      for promoter elements shorter than 364 bp. Two upstream activating regions, -3600
      to -2033 and -2033 to -882, enhanced GUS expression in seeds. The -882 to -364
      region was sufficient to confer seed-specific expression of GUS when fused to a -
      64/ + 6CaMV 35S minimal promoter. Expression from the ABI3 promoter constructs
      was seed-specific, except in the presence of exogenous abscisic acid (ABA) (>0.3
      microM), when GUS expression was detected in seedling roots. Excision of a 405 bp
      region containing three upstream open reading frames (uORFs) from the 5'-UTR
      dramatically increased GUS expression and debilitated constraint of reporter
      expression in roots. Negative regulation of ABI3 expression by the 5'-UTR may
      involve a post-transcriptional mechanism analogous to that of tumor suppressor
      genes which also bear long, uORF-containing, 5'-UTRs, or through interactions
      with RNA-binding proteins.

PMID- 15159633
TI  - A small family of LLS1-related non-heme oxygenases in plants with an origin
      amongst oxygenic photosynthesizers.
AB  - Conservation of Lethal-leaf spot 1 (Lls1) lesion mimic gene in land plants
      including moss is consistent with its recently reported function as pheophorbide
      a oxygenase (Pao) which catalyzes a key step in chlorophyll degradation
      (Pruzinska et al., 2003). A bioinformatics survey of complete plant genomes
      reveals that LLS1(PAO) belongs to a small 5-member family of non-heme oxygenases
      defined by the presence of Rieske and mononuclear iron-binding domains. This gene
      family includes chlorophyll a oxygenase (Cao), choline monooxygenase (Cmo), the
      gene for a 55 kDa protein associated with protein transport through the inner
      chloroplast membrane (Tic 55) and a novel 52 kDa protein isolated from
      chloroplasts (Ptc 52). Analysis of gene structure reveals that these genes
      diverged prior to monocot/dicot divergence. Homologues of LLS1(PAO), CAO, TIC55
      and PTC52 but not CMO are found in the genomes of several cyanobacteria.
      LLS1(PAO), PTC52, TIC55 and a set of related cyanobacterial homologues share an
      extended carboxyl terminus containing a novel F/Y/W-x(2)-H-x(3)-C-x(2)-C motif
      not present in CAO. These proteins appear to have evolved during the transition
      to oxygenic photosynthesis to play various roles in chlorophyll metabolism. In
      contrast, CMO homologues are found only in plants and are most closely related to
      aromatic ring-hydroxylating enzymes from soil-dwelling bacteria, suggesting a
      more recent evolution of this enzyme, possibly by horizontal gene transfer. Our
      phylogenetic analysis of 95 extant non-heme dioxygenases provides a useful
      framework for the classification of LLS1(PAO)-related non-heme oxygenases.

PMID- 15159634
TI  - Dynamics of the evolution of orthologous and paralogous portions of a complex
      locus region in two genomes of allopolyploid wheat.
AB  - Two overlapping bacterial artificial chromosome (BAC) clones from the B genome of
      the tetraploid wheat Triticum turgidum were identified, each of which contains
      one of the two high-molecular-weight (HMW) glutenin genes, comprising the complex
      Glu-B1 locus. The complete sequence (285 506 bp of DNA) of this chromosomal
      region was determined. The two paralogous x-type ( Glu-1-1 ) and y-type ( Glu-1-2
      ) HMW-glutenin genes of the complex Glu-B1 locus were found to be separated by
      ca. 168 000 bp instead of the 51 000 bp separation previously reported for the
      orthologous Glu-D1 locus of Aegilops tauschii, the D-genome donor of hexaploid
      wheat. This difference in intergene spacing is due almost entirely to be the
      insertion of clusters of nested retrotransposons. Otherwise, the orientation and
      order of the HMW glutenins and adjacent genes were identical in the two genomes.
      A comparison of these orthologous regions indicates modes and patterns of
      sequence divergence, with implications for the overall Triticeae genome structure
      and evolution. A duplicate globulin gene, found 5' of each HMW-glutenin gene,
      assists to tentatively define the original duplication event leading to the
      paralogous x- and y-type HMW-glutenin genes. The intergenic regions of the two
      loci are composed of different patterns and classes of retrotransposons,
      indicating that insertion times of these retroelements were after the divergence
      of the two wheat genomes. In addition, a putative receptor kinase gene near the y
      type HMW-glutenin gene at the Glu-B1 locus is likely active as it matches
      recently reported ESTs from germinating barley endosperm. The presence of four
      genes represented only in the Triticeae endosperm ESTs suggests an endosperm
      specific chromosome domain.

PMID- 15159635
TI  - KNAT6 gene of Arabidopsis is expressed in roots and is required for correct
      lateral root formation.
AB  - As part of a programme to determine whether root development requires a pathway
      involving KNOTTED-like homeobox ( KNOX ) genes, we cloned the KNAT6 cDNA, a
      member of the KNOX gene family in Arabidopsis, from root tissue. The KNAT6 cDNA
      is represented by two isoforms, suggesting that the KNAT6 transcript is subject
      to alternative splicing. Promoter-reporter and RT-PCR analysis confirms
      expression of the KNAT6 gene in roots, and in particular in the phloem tissue
      close to the site of lateral root initiation, though not in the primary or
      lateral root meristem. The KNAT6 gene promoter activity is altered in pattern by
      treatment with exogenous auxin and in the rooty mutant background, with
      expression shifting distally in the root. In contrast, exogenous cytokinin
      suppresses KNAT6 promoter activity. KNAT6::GFP fusion protein is localized to the
      nucleus, consistent with the predicted function of KNAT6 as a transcription
      factor. Over-expression of the more abundant shorter isoform of the KNAT6 cDNA,
      but not of the less abundant longer form, leads to a lobed leaf phenotype, but no
      consistently aberrant root phenotype. Down-regulation of KNAT6 expression by RNA
      interference was associated with an increased total number of lateral roots.
      These data indicate a role for KNAT6 in modulating lateral root formation.

PMID- 15159636
TI  - Identification and characterization of proteins that interact with the carboxy
      terminus of poly(A)-binding protein and inhibit translation in vitro.
AB  - Poly(A)-binding proteins (PABPs) are multifunctional proteins that play important
      roles in mRNA stability and protein translation. Two cucumber ( Cucumis sativus
      L.) proteins, PCI6 (PABP-CT-interacting) and PCI243 were identified based on
      ability to interact with the carboxy terminus (CT) of PABP in yeast two-hybrid
      and in vitro binding assays. PCI6 and PCI243 share a conserved amino acid domain
      (SxLnpnApxFxP) in common with human PABP-CT interactors, and with Arabidopsis
      ERD15 (early-responsive to dehydration). Deletion analysis and point mutations
      indicate that presence of this domain is necessary for the interaction, and tests
      with ERD15 demonstrate that it is predictive of interaction. Other plant proteins
      possessing this domain fall into two categories: small, acidic proteins like
      PCI6, PCI243 and ERD15, and larger neutral proteins that also include an RNA
      recognition motif. PCI6 is expressed in a range of tissues, e.g., leaves, roots,
      stems and flowers, and follows a diurnal pattern of expression, increasing during
      light hours and declining overnight. In wheat germ and mouse ascites Krebs-2 in
      vitro translation systems, PCI6 inhibited translation whereas the non-interacting
      mutant, PCI6-23A, did not or had a greatly reduced effect. The activity of PCI6,
      therefore, is reminiscent of that of human PABP-interacting protein 2 (Paip2).
      These results demonstrate a novel interaction between PABP and several plant
      proteins sharing a SxLnpxApxFxP motif, with possible implications for
      translational regulation.

PMID- 15159637
TI  - Isolation and identification of a gene in response to rice blast disease in rice.
AB  - We combined cDNA amplified fragment length polymorphism (cDNA-AFLP) with bulked
      segregant analysis (BSA) to detect genes that control rice blast ( Magnaporthe
      grisea ) resistance in a double-haploid (DH) population derived from a cross
      between a blast-resistant variety, Zhai Ye Qing8 (ZYQ8), and a blast-susceptible
      variety, Jin Xi17 (JX17). In cDNA-AFLP analysis between a blast resistance (R)
      pool and a blast susceptibility (S) pool from the DH population, 12 transcript
      derived fragments (TDFs) that were present in only one of the two pools were
      detected, 8 of which were from the R pool and 4 from the S pool. Mapping analysis
      of these TDFs by using the DH mapping population showed that five of them, R1,
      R8, S9, S16 and S17, were located on chromosome 1. Sequence comparison and
      allelic analysis showed that R1/S16 and R8/S9 were two pairs of allelic genes.
      The full-length cDNA sequences of R1/S16, S17 and R8/S were obtained through cDNA
      library screening, in which only the expression level of R8 cDNA was up-regulated
      by inoculation with the blast isolate zh10814 and not affected by mock treatment,
      suggesting that R8 was implicated in the signaling pathways of the rice blast
      resistance reaction. Protein function prediction showed that R8 cDNA encodes a
      protein with high identity to a putative calmodulin-binding protein in
      Arabidopsis thaliana which belongs to the P-loop-containing nucleotide
      triphosphate hydrolases superfamily that contains a number of various kinases.

PMID- 15159638
TI  - Functional definition of ABA-response complexes: the promoter units necessary and
      sufficient for ABA induction of gene expression in barley ( Hordeum vulgare L.).
AB  - Abscisic acid (ABA)-response promoter complexes (ABRCs), consisting of an ACGT
      core-containing element (ACGT box) and a coupling element (CE), have been shown
      to be necessary and sufficient for ABA induction of gene expression in cereal
      plants. In this work, the component elements of two ABRCs are defined in terms of
      base sequence, orientation, and distance from each other. The ACGT element
      requires the sequence 5'-ACGTGGC-3' and the elements CE1 and CE3 require the
      sequences CCACC and GCGTGTC, respectively. The ACGT element and CE3 are next to
      each other in the barley ABA-inducible gene HVA1, and lengthening the distance
      between them gradually decreases their activity in conferring ABA response. On
      the other hand, the ACGT element and CE1 are separated by about 20 bp in the
      promoter of another ABA-inducible gene, HVA22, and need to be separated by
      multiples of 10 bp in order to confer high ABA induction, suggesting that these
      two elements have to be located in the same side of the DNA double helix.
      Although the coupling between an ACGT box and a CE is sufficient for ABA
      induction, two copies of the ACGT element are equally active. However, two copies
      of CE3 appear to be less active. Specific interactions between ABRC and nuclear
      proteins have been detected. In vitro binding activities of nuclear proteins to
      an ABRC and to its mutant forms appear to be proportional to the biological
      activities of these sequences in vivo. Our data suggest that the specific
      response to ABA is determined by the presence of two ACGT boxes or an ACGT box
      plus a CE as well as by the flanking sequences of the ACGT boxes and the CEs.

PMID- 15159639
TI  - Isolation and characterization of Fe(III)-chelate reductase gene LeFRO1 in
      tomato.
AB  - Tomato is a model plant for studying molecular mechanisms of iron uptake and
      metabolism in strategy I plants (dicots and non-graminaceous monocots). Reduction
      of ferric to ferrous iron on the root surface is an obligatory process for iron
      acquisition from soil in these plants. LeFRO1 encoding an Fe(III)-chelate
      reductase protein was isolated from the tomato genome. We show that expression of
      LeFRO1 in yeast increases Fe(III)-chelate reductase activity. In a transient
      expression analysis we found that LeFRO1 protein was targeted on the plasma
      membrane. LeFRO1 transcript was detected in roots, leaves, cotyledons, flowers
      and young fruits by RT-PCR analysis. Abundance of LeFRO1 mRNA was much lower in
      young fruits than in other tissues. The transcription intensity of LeFRO1 in
      roots is dependent on the iron status whereas it is constitutively expressed in
      leaves. These results indicate that LeFRO1 is required in roots and shoots as
      well as in reproductive organs for iron homeostasis and that its transcription in
      roots and shoots is regulated by different control mechanisms. The expression of
      LeFRO1 was disrupted in the iron-inefficient mutants chloronerva and T3238 fer,
      indicating that FER and CHLN genes are involved in the regulation of LeFRO1
      expression in tomato roots. The differential expression of LeFRO1 and LeIRT1 (an
      iron-regulated metal transporter gene in tomato) in roots of T3238 fer under iron
      deficient and -sufficient conditions suggests that the FER gene may regulate
      expression of LeFRO1 more directly than that of LeIRT1 in tomato roots.

PMID- 15159640
TI  - Over-expression of a scopoletin glucosyltransferase in Nicotiana tabacum leads to
      precocious lesion formation during the hypersensitive response to tobacco mosaic
      virus but does not affect virus resistance.
AB  - Nicotiana tabacum Togt encodes a scopoletin glucosyltransferase
      (UDPglucose:scopoletin O -beta-D-glucosyltrans- ferase, EC 2.4.1.128) known to
      act in vitro on many different substrates including the 6-methoxy-7-hydroxy-
      coumarin scopoletin. This phenolic compound accumulates in vast amounts,
      essentially in its glucosylated form scopolin, in tobacco during the
      hypersensitive response (HR) to tobacco mosaic virus (TMV). To identify the
      physiological role of this pathogen-inducible UDP-Glc glucosyltransferase (UGT),
      we generated TOGT over-expressing transgenic plants. Although no endogenous
      scopoletin or scopolin could be detected before infection, the accumulation of
      both the aglycone and the glucoside was found to be 2-fold higher in transgenic
      plants after inoculation with TMV than in wild-type plants. Scopoletin UGT
      activity in plants over-expressing Togt was significantly higher during the HR
      than in control plants. This up-regulated activity was associated with a strong
      increase of the bright blue fluorescence surrounding the HR-necrotic lesions
      under UV light, which is known to correlate with scopoletin and scopolin
      abundance. Necrosis appeared sooner in transgenic plants and lesions developed
      faster, suggesting an accelerated HR. Unexpectedly, the viral content in each
      lesion was not significantly different in transgenic and in wild-type plants.
      These results are discussed in relation to the role of TOGT as the major UDP-Glc:
      scopoletin glucosyltransferase and to the importance of scopoletin accumulation
      during the HR.

PMID- 15159641
TI  - Cloning and functional analyses of a gene from sugar beet up-regulated upon cyst
      nematode infection.
AB  - The cDNA-AFLP technique was used to isolate sugar beet genes up-regulated upon
      infection with the beet cyst nematode Heterodera schachtii. Hairy root cultures
      were obtained from resistant plants carrying a Beta procumbens translocation as
      well as from a non-resistant control. mRNA was isolated from hairy root clones
      and sugar beet plants infected or not with the beet cyst nematode and 8000
      transcript-derived fragments (TDFs) were analysed. One TDF was found to be
      differentially expressed in both materials and was further investigated. Real
      time PCR confirmed that this TDF is specifically up-regulated in resistant sugar
      beet upon nematode infection and its full-length cDNA was isolated. Sequence
      analysis suggests that the gene encodes a 317 amino acid polypeptide of unknown
      function. No homology to any sequence present in the public databases could be
      detected. To further elucidate its function in resistance to the beet cyst
      nematode, the cDNA was transformed into hairy roots of susceptible sugar beet
      under the control of the 35S promoter and hairy root clones were inoculated with
      nematodes. The number of developing females was significantly reduced in 12 out
      of 15 clones resulting from independent transgenic events suggesting that the
      gene can be used for inducing cyst nematode resistance in plants.

PMID- 15159642
TI  - Executive function impairment in early-treated PKU subjects with normal mental
      development.
AB  - Executive functions were studied in 14 early and continuously treated PKU
      subjects (age 10.8 years, range 8-13) in comparison with controls matched for IQ,
      sex, age and socioeconomic status. Brain MRI examination was normal in all PKU
      patients. Neuropsychological evaluation included Wisconsin Card Sorting Test, Rey
      Osterreith Complex Figure Test, Elithorn's Perceptual Maze Test, Weigl's Sorting
      Test, Tower of London, Visual Search and Motor Motor Learning Test. Whatever the
      IQ, PKU subjects performed worse than controls in tests exploring executive
      functions. Subgrouping the PKU subjects according to the quality of dietary
      control for the entire follow-up period (using 400 micromol/L as cut-off value
      for blood phenylalanine (Phe) concentration) showed that patients with worse
      dietary control performed more poorly than both the PKU group with the best
      dietary control and the control group. However, a mild impairment of executive
      functions was still found in PKU patients with a good dietary control (Phe <400
      micromol/L) compared to controls. Concerning the PKU group as a whole, no linear
      correlation was found between neuropsychological performance and historical and
      concurrent biochemical parameters. We conclude that (a) PKU patients, even when
      treated early, rigorously and continuously, show an impairment of frontal lobe
      functions; (b) a protracted exposure to moderately high levels of Phe can affect
      frontal lobe functions independently of the possible effect of the same exposure
      on IQ; (c) in order to reduce the risk of frontal lobe dysfunction, the target of
      dietary therapy should be to maintain blood Phe concentration below 400
      micromol/L.

PMID- 15159643
TI  - A new, low-volume protein substitute for teenagers and adults with
      phenylketonuria.
AB  - Some older patients with phenylketonuria (PKU) fail to consume their protein
      substitute (with or without vitamin and mineral supplements) in prescribed
      amounts, which contributes to poor blood phenylalanine control. PKU Express
      (Vitaflo), is a new low-volume (amino acids 72 g/100 g), low-carbohydrate,
      phenylalanine-free protein substitute with added vitamins and minerals designed
      for people with PKU over 8 years of age. In an open intervention study, the aim
      was to investigate its acceptability and effectiveness in a group of teenagers
      and adults with PKU. Twenty-three subjects (15 female; 8 male) with PKU, who had
      a median age of 17 years (range 8-37 years) took the substitute for 8 weeks. A 3
      day prospective diet diary, height, weight, plasma amino acids, biochemical and
      haematological nutritional analytes were measured at weeks 0 and 8. Skin-puncture
      bloods for plasma phenylalanine were collected every 2 weeks. The median weight
      of protein substitute (with or without vitamin and mineral supplements) consumed
      decreased by 33% from 150 g (range 140-180) daily to 100 g (range 100-125) daily
      ( p <0.001). Median change in energy intake decreased by a median of 10% (95% CI
      2.0 to 18.0) when compared to intake on original protein substitute. On PKU
      Express, the intakes of all nutrients exceeded the dietary reference values but
      none was excessively high. Blood phenylalanine decreased by a mean of 37
      micromol/L (95% CI-27 to 102) during the trial. Body mass index decreased in 40%
      of subjects. Changes in blood phenylalanine or body mass index were not
      statistically significant. Most of the nutritional, haematological and
      biochemical indices stayed within normal reference ranges for the analytes
      studied. Sixteen (70%) of the subjects had low plasma selenium at the start, but
      only 13 (57%) at the study end. Plasma vitamin B12 was high in 8 subjects at the
      start of the study and 9 at the end. Twenty-one subjects (96%) stated that the
      product was convenient and easy to prepare. However, 7 (32%) described the smell
      and 9 (46%) the texture as the same as or worse than those of previous protein
      substitutes. Because of the use of the premeasured sachets, some subjects were
      able to prepare their own protein substitute for the first time. PKU Express is a
      safe, efficacious, protein substitute that significantly reduces the daily volume
      of prescribed protein substitute.

PMID- 15159644
TI  - Prevalence of stimulant use for attentional dysfunction in children with
      phenylketonuria.
AB  - Recent data suggest that children with phenylketonuria (PKU) and poor metabolic
      control may have an increased prevalence of attentional dysfunction. However, few
      formal studies have addressed this topic in detail. We reviewed the medical
      records of 38 school-aged children with early and continuously treated PKU to
      determine the prevalence of stimulant use for attentional dysfunction, and to
      determine the relationship between metabolic control and attentional symptoms.
      Twenty-six per cent of the PKU children used a stimulant medication for
      attentional dysfunction. This is significantly higher than in an age- and sex
      matched control group consisting of children with type I diabetes mellitus (6.5%,
      p <0.006), and also considerably higher than population norms for attention
      deficit hyperactivity disorder (ADHD) (5%). We also found a significant
      relationship between phenylalanine levels and stimulant use or attentional
      symptoms. Mean plasma phenylalanine concentration was 486 micromol/L in the non
      stimulant-using group and 792 micromol/L in the stimulant-using group (p <0.02).
      Mean phenylalanine concentration was 462 micromol/L in the group not reporting
      attentional symptoms, and was 702 micromol/L in the symptomatic group (p <0.05).
      Parents of the stimulant-using children felt that the stimulants were efficacious
      in treating their child's attentional symptoms. Stimulant use and parent reports
      of attentional dysfunction are quite common in our PKU patients and appear to be
      strongly related to higher phenylalanine concentrations.

PMID- 15159645
TI  - The Resource Mothers Study of Maternal Phenylketonuria: preliminary findings.
AB  - Women with phenylketonuria (PKU) must follow a strict low-phenylalanine diet
      during pregnancy in order to protect the fetus from the deleterious effects of
      high maternal blood phenylalanine. The Resource Mothers Study of Maternal PKU was
      undertaken to determine whether a home visitation programme was effective in
      helping women with PKU attain blood phenylalanine control earlier during
      pregnancy. Resource Mothers were trained to provide social support and practical
      assistance to women with PKU during pregnancy. Eight metabolic clinics in the
      United States participated in the study. Women with PKU who were planning
      pregnancy or already pregnant were enrolled in the study and were treated with a
      low-phenylalanine diet aimed at controlling blood phenylalanine to 120-360
      micromol/L. They were randomly assigned to receive the services of a Resource
      Mother (RM group) or to a control group. Fifty women were enrolled, and accounted
      for 44 pregnancies which resulted in 28 live births, and 6 spontaneous abortions.
      Ten women are currently pregnant and another 6 have not become pregnant. Fifty
      six percent of enrolled women began the diet prior to becoming pregnant. Fifty
      three percent of women in the Resource Mother group were in metabolic control by
      10 weeks gestation as compared to 39% in the control group. In addition, women
      who began diet after pregnancy and had a Resource Mother attained metabolic
      control earlier (mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks
      in the control group). There was no difference in birth measurement z -scores of
      offspring born to women in the RM group compared to controls. All but 4 women
      rated themselves as feeling worse about the diet at the end of pregnancy than at
      the beginning, and few women in either group remained on diet after delivery.

PMID- 15159646
TI  - Discordant PKU phenotype in one family due to disparate genotypes and a novel
      mutation.
AB  - Classical phenylketonuria (PKU) and mild hyperphenylalaninaemia (MHP) are two
      ends of the broad diagnostic spectrum in phenylalanine hydroxylase (PAH)
      deficiency. We have analysed a family in which classical PKU, MHP and a normal
      phenotype occurred in family members with different mutations. Sequence analysis
      revealed three mutations segregating in the family. The individual with classical
      PKU had two previously reported deleterious mutations. A third novel mutation was
      identified in the other two individuals. This report demonstrates that when
      discordant phenotypes occur in a family, without protein loading or phenylalanine
      tolerance test, complete analysis of the PAH gene may be performed in order to
      support the diagnosis and assist in accurate genetic counselling and patient
      management.

PMID- 15159647
TI  - Tetrahydrobiopterin deficiency and dopamine loss in a genetic mouse model of
      Lesch-Nyhan disease.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is an enzyme that catalyses
      the conversion of hypoxanthine and guanine into their respective nucleotides.
      Inherited deficiency of the enzyme is associated with a loss of striatal dopamine
      in both mouse and man. Although HPRT is not directly involved in the metabolism
      of dopamine, it contributes to the supply of GTP, which is used in the first and
      rate-limiting step in the synthesis of tetrahydrobiopterin (BH4). Since BH4 is
      required as a cofactor for tyrosine hydroxylase in the synthesis of dopamine, any
      limitation in the supply of GTP could interfere with the synthesis of dopamine.
      The current studies were designed to address the hypothesis that the reduced
      striatal dopamine in mice with HPRT deficiency results from reduced availability
      of BH4. The mutant mice had small reductions in striatal BH4, with normal BH4
      levels in other brain regions. Liver BH4 was normal in HPRT-deficient mutant
      mice, and a phenylalanine challenge test failed to reveal any evidence for
      impaired hepatic phenylalanine hydroxylase, another BH4-dependent enzyme.
      Although striatal BH4 content is not normal, supplementation with BH4 or L-dopa
      failed to correct the striatal dopamine deficiency of the mutant mice, suggesting
      that BH4 limitation is not responsible for the dopamine loss.

PMID- 15159648
TI  - How reliable is the allopurinol load in detecting carriers for ornithine
      transcarbamylase deficiency?
AB  - The allopurinol test aims to distinguish carriers and noncarriers for ornithine
      transcarbamylase (OTC) deficiency. We have evaluated the reliability of the test
      in at-risk females of known genotype. Results based on urine orotidine and/or
      orotic acid measurement were compared in terms of sensitivity and specificity.
      Retrospectively, we analysed the results of allopurinol tests in 42 women (22
      confirmed heterozygotes and 20 noncarriers) from 23 pedigrees at risk of being
      carriers for OTC deficiency. Using a cut-off of 2 standard deviations above the
      mean of controls, the highest sensitivity (91%) was given by orotidine alone or
      in combination with orotic acid, but specificity was only 70% and 65%,
      respectively. We conclude that the value of the allopurinol test for detecting
      OTC carriers in at-risk females is limited. This needs to be recognized when
      counselling families. The test still has a role as a safe, quick, noninvasive
      screen of individuals at risk, but test results in possible carriers should be
      interpreted with caution. In the absence of other supportive evidence,
      confirmation by mutation analysis is required.

PMID- 15159649
TI  - Low-protein diet and progression of retinal degeneration in gyrate atrophy of the
      choroid and retina: a twenty-six-year follow-up.
AB  - Gyrate atrophy of the choroid and retina is an autosomal recessive chorioretinal
      dystrophy which leads to a slowly progressive loss of vision. The primary defect
      is due to a deficiency of the enzyme ornithine delta-aminotransferase, which is
      responsible for markedly elevated levels of ornithine in plasma and other body
      fluids. Although several therapeutic regimens have been proposed, the reduction
      in ornithine accumulation obtained by reducing the intake of its precursor
      arginine (semisynthetic low-arginine diet) is the one most practised. In this
      clinical and molecular study we report a patient with hyperornithinaemia and
      gyrate atrophy of the choroid and retina who had been diagnosed when she was 3
      years 9 months old. She also presented mild mental retardation, delayed language
      development and speech defects. The patient has recently been found to be
      homozygous for the new Gly91Arg amino acid substitution of the enzyme ornithine
      delta-aminotransferase. This mutation lies in a region of the mature protein that
      is considered crucial for the mitochondrial targeting activity. In this patient,
      a 28-year treatment with a completely natural low-protein diet (0.8 g/kg per day
      of natural protein) has been able to significantly reduce ornithine plasma
      levels, and to greatly delay the natural progression of the chorioretinal
      changes. This study suggests that, in the long-term treatment of gyrate atrophy,
      the efficacy in slowing the progression of chorioretinal changes and the
      palatability of a completely natural low-protein diet make this treatment a
      potentially viable alternative in patients refusing the semisynthetic diet.

PMID- 15159650
TI  - Maternal histidinaemia: pregnancies and offspring outcomes.
AB  - Untreated pregnancies and their outcomes were studied in 10 women with
      histidinaemia and their 26 pregnancies. The mean maternal assigned histidine
      level was 727+/-186 micromol/L (range 484-1,053). Six women had classic
      histidinaemia (assigned level >700 micromol/L) and the remaining four had mild
      (atypical) histidinaemia. The pregnancies were uneventful, with only one
      spontaneous loss and 25 live births. Birth measurements were normal and no
      congenital anomalies were observed. Growth and development were normal in all
      offspring. IQ among the 23 offspring tested was 103+/-12 (range 79-122). Four
      offspring required special education for brief periods and one for several years,
      but this frequency, as well as that of 12% for attention deficit hyperactive
      disorder, was not significantly different from expected in the general
      population. It would appear that maternal histidinaemia, unlike maternal
      phenylketonuria, can be added to the list of maternal inborn errors of metabolism
      that are nonteratogenic.

PMID- 15159651
TI  - Living-donor liver transplantation for propionic acidaemia.
AB  - Three patients with the severe form of propionic acidaemia were treated with
      living-donor liver transplantation (LDLT). The procedure was successful for all
      patients and the incidence of metabolic decompensation was reduced dramatically
      even without protein restriction. Biochemically, however, the improvement was not
      significant and the patients continued to excrete large amounts of propionic acid
      metabolites. One of the patients experienced a severe acidaemic episode 3 years
      after transplantation. LDLT has a beneficial effect on the care of severely
      affected patients since it reduces the risk of metabolic decompensation and
      improves the quality of life with less strict dietary control. Adequate protein
      restriction and medication need to be maintained even after successful
      transplantation.

PMID- 15159652
TI  - Intrastriatal malonate administration induces convulsive behaviour in rats.
AB  - Malonic acidaemia is an inborn error of metabolism that accumulates malonate, a
      competitive succinate dehydrogenase (SDH; EC 1.3.99.1) inhibitor. The present
      study investigated the behavioural effects of unilateral intrastriatal
      administration of malonate (0.6, 1.8 or 6 micromol) in adult male Wistar rats
      (n=10-13). Low doses of malonate (1.8 micromol) decreased exploratory activity
      and caused ipsiversive rotational behaviour. High doses of malonate (6 micromol)
      induced contralateral rotational behaviour and convulsive episodes. Malonate
      competitively inhibited SDH in mitochondrion-enriched fractions from striatum (
      Ki=0.034+/-0.008 mmol/L). Interestingly, methylmalonate, which is a weaker SDH
      inhibitor than malonate (Ki=4.22+/-1.3 mmol/L), induced more convulsions than
      malonate at equimolar doses and did not cause ipsiversive rotational behaviour.
      It is suggested that the potency of SDH inhibition in vitro does not correlate
      positively with the convulsant potential of these inhibitors in vivo.

PMID- 15159653
TI  - Clinical benefit in Fabry patients given enzyme replacement therapy--a case
      series.
AB  - Fabry disease is a rare lysosomal storage disorder resulting from deficient
      activity of alpha-galactosidase A and subsequent pathological accumulation of
      glycosphingolipids throughout the body. Traditionally, Fabry disease was managed
      symptomatically, but the introduction of enzyme replacement therapies (ERTs)
      (agalsidase beta (Fabrazyme); agalsidase alfa (Replagal)) has transformed
      treatment of this disorder. Clinical studies of both compounds have demonstrated
      clearance of glycosphingolipds from key tissues. To explore whether substrate
      clearance translates into clinical benefit, a retrospective survey of 17 patients
      (mean age 34.7 years) treated with agalsidase beta (1 mg/kg every 2 weeks) was
      undertaken, using an eight-item retrospective questionnaire developed
      specifically to assess the effect of ERT on the symptoms of Fabry disease. Pain
      severity, heat tolerance, physical activity, fatigue and psychological status
      were scored using a 10-point visual analogue scale (e.g. for pain severity:
      1=none, 10=strong). Answers to all other questions were quantitative. Changes in
      mean scores were 4.69 to 2.25 (p =0.012) for pain severity; 4.38 to 2.21 (p
      =0.019) for number of pain crises per month; 8.69 to 2.98 (p =0.097) for duration
      of pain crises in hours; 2.76 to 5.76 (p =0.002) for heat tolerance; 3.28 to 2.51
      (p =0.058) for bowel movements per day; 2.47 to 4.47 (p =0.007) for frequency of
      physical activity; 5.53 to 3.71 (p =0.046) for fatigue, and 5.82 to 8.12 (p
      =0.005) for psychological status. All patients improved in at least one aspect,
      although the degree of improvement across patients and aspects varied widely;
      reasons for this remain unclear. Despite the inherent bias involved in
      retrospective questionnaires, we believe that the findings are encouraging. A
      prospective version of the questionnaire is currently under validation.

PMID- 15159654
TI  - CNS involvement in Fabry disease: clinical and imaging studies before and after
      12 months of enzyme replacement therapy.
AB  - We report the clinical and radiological central nervous system (CNS) findings of
      8 Fabry disease patients, before (8/8) and after (7/8) 12 months of enzyme
      replacement therapy (ERT) with agalsidase-alpha. Eight biochemically proven Fabry
      disease patients (from four families) were included. Patients were evaluated at
      baseline and at regular intervals during 12 months of ERT. Evaluations included a
      thorough, standardized neurological examination, and magnetic resonance imaging
      (MRI) and angiography (MRA). Brain proton magnetic resonance spectroscopy (MRS)
      was also performed in 5/8 patients. The presence and location of grey- and white
      matter lesions, the presence of vascular occlusion or ectasia on MRA and the
      metabolite ratios on MRS were determined, as well as their relation to age,
      symptoms and neurological examination. Neurological examination showed few
      abnormalities in these patients: scores varied (on a 0-100 scale) from zero to 5,
      at baseline and in the 12th month of ERT. The most consistent findings on MRI
      were asymmetric, widespread patterns of deep white-matter (WM) lesions,
      hyperintense on T2 and FLAIR-weighted images, found in 4/8 patients at baseline,
      predominantly in frontal and parietal lobes. These lesions did not correlate with
      other clinical variables, although there was a trend towards an association of
      the lesions with age and hearing loss. The youngest patient with MRI lesions was
      24 years old. After 12 months of ERT, MRI was normal in 3/7, showed the same WM
      lesions in 2/7, and showed worsening of WM lesions in 2/7 patients (from the same
      family). Abnormal MRS metabolite ratios were detected at baseline in 4/5
      patients. While neurological examination remained almost normal during the 12
      months of ERT, new small-vessel CNS involvement still appeared in 2/7 patients.
      We do not know why ERT was not able to prevent this in these two related male
      patients. This could be due either to their older ages (46 and 36 years), or to a
      more pathogenic mutation. We conclude that MRI was more sensitive than
      neurological examination in detecting CNS involvement and progression in Fabry
      disease in the time interval studied.

PMID- 15159655
TI  - Juvenile Sandhoff disease--nine new cases and a review of the literature.
AB  - Juvenile Sandhoff disease (McKusick 268800) is a rare lysosomal storage disorder
      with only 12 cases recorded in the literature. This condition is also referred to
      as the subacute form of hexosaminidase deficiency. We describe 9 new cases of
      Pakistani origin and compare these with the other published cases. Ataxia and
      speech abnormalities were the commonest presentation. Constipation and urinary
      incontinence were frequent and may be due to autonomic neuropathy. Cherry-red
      spot was not noted in any of our cases. Increased lower limb reflexes were the
      commonest physical finding. Significant delay in diagnosis may be due to the
      nonspecific presentation of this condition. Diagnosis was on the basis of
      hexosaminidase deficiency. Residual enzyme activity did not correlate with the
      clinical picture. Emerging therapies make early diagnosis of this disorder
      important.

PMID- 15159658
TI  - Tiotropium (Spiriva) for COPD.

PMID- 15159656
TI  - Pro-oxidant and antioxidant factors in acute intermittent porphyria: family
      studies.
AB  - Given the crucial role of iron and porphyrins in oxidative cellular damage in the
      chronic porphyrias, we undertook an extensive study in families with acute
      porphyrias to evaluate the possible role of similar oxidative damage in these
      diseases, whose natural history is often also complicated by neoplastic
      evolution. Four unrelated patients with acute intermittent porphyria (AIP) were
      studied together with 37 members of four different families. Aminolevulinic acid
      and porphobilinogen were measured in urine, and porphyrins in urine, plasma and
      stools. The activity of the congenitally deficient enzyme, porphobilinogen
      deaminase, and the concentrations of plasma iron, transferrin, ferritin, and
      various antioxidants (ascorbic acid, retinol, tocopherol, alpha- and beta
      carotene, by a personal HPLC method) and the urinary and plasma metabolites of
      nitrous oxide were also assayed. The results showed no relationship between the
      observed increase of porphyrin metabolites and the presence of markers of
      oxidative damage or the decrease of circulating antioxidants: however, when such
      a decrease was registered, it depended on spontaneous or iatrogenic iron
      accumulation. We conclude that family screening, recommended for the
      identification of AIP carriers, must also include evaluation of iron stores with
      a view to preventing the oxidative damage and in order to forestall the
      neoplastic evolution of the disease.

PMID- 15159660
TI  - Cosmetic phalloplasty.

PMID- 15159657
TI  - Carnitine-acylcarnitine translocase deficiency: identification of a novel
      molecular defect in a Bedouin patient.
AB  - Carnitine-acylcarnitine translocase CACT deficiency is a very rare autosomal
      recessive disease. The neonatal phenotype of CACT deficiency is characterized by
      hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy and skeletal muscle
      weakness culminating in early death. The disease is caused by mutations in the
      CACT gene, which encodes a protein transporting long-chain fatty acid carnitine
      esters into the mitochondrial matrix. In this report, we describe the first case
      of CACT deficiency in the Bedouin population in Israel. The patient, the first
      son of consanguineous parents, was born at term after uneventful delivery. During
      the second day of life, he developed clinical signs of an acute metabolic crisis
      with severe hypoglycaemia and hyperammonaemia. Biochemical investigation
      suggested the diagnosis of CACT deficiency. Genetic molecular analysis confirmed
      this diagnosis by demonstrating that the affected child was homozygous for a
      novel missense mutation 793A>G, substituting glutamine by arginine (Q238R) in
      exon 7 of the CACT gene. Despite medical treatment and adequate nutrition, the
      patient died at 6 months of age.

PMID- 15159659
TI  - Imiquimod (Aldara) for actinic keratoses.

PMID- 15159661
TI  - [Picture perception and psychology of vision].

PMID- 15159662
TI  - [Contrast imaging technology of ultrasound].

PMID- 15159663
TI  - [Why graduate school for working people?].

PMID- 15159664
TI  - [Clinical application of X-ray measurement using Monte Carlo simulation (EGS4)].

PMID- 15159665
TI  - [Explanation of the draft "Release of patients after therapy with unsealed
      radionuclides" of the International Commission On Radiological Protection: the
      1st report].

PMID- 15159666
TI  - [New hope for winning the war against cancer: IMRT=intensity-modulated-radiation
      therapy--Part 11].

PMID- 15159667
TI  - [Reduction of reconstruction time and data volume of sinogram by angular
      compression for clinical three-dimensional whole body FDG-PET].
AB  - In positron emission tomography (PET), the large number of lines of responses in
      three-dimensional (3D) acquisition mode creates a high volume of sinogram data
      and increases reconstruction time in iterative reconstruction. We tried to
      decrease sinogram data volume by reducing the number of views using angular
      compression and then evaluated the accuracy of this mashed mode. Three methods
      were compared, conventional mode (CONV), X2 mashed mode (X2: two adjacent
      projection angles are added together), and X4 mashed mode (X4: four adjacent
      angles added). A point source of (18)F was used to measure spatial resolution. A
      hot spot phantom made of 6 hot spheres (10-38 mm in diameter) within water of 20
      cm in diameter was scanned to evaluate the recovery coefficient (RC). A lung
      heart-liver phantom made of homogeneous radioactive myocardium, a spherical hot
      mass in the lung (10 mm in diameter), and background activity in the liver was
      scanned to evaluate the homogeneity of the myocardial wall. The quality of the
      reconstructed images was evaluated in terms of the normalized mean square error
      (NMSE), Bull's eye map, profile curve, and peak value of the spherical hot mass.
      The reconstruction times of X2 and X4 were one-half and one-quarter,
      respectively, of that of CONV. In terms of spatial resolution, FWHM of CONV, X2,
      and X4 were, 4.26, 4.33, and 4.48 (mm) at the center, 4.81, 5.68, and 8.73
      tangentially, and 8.01, 8.19, and 8.27 radially at R=200 mm, respectively. RC was
      similar for all methods. The NMSE values of X2 and X4 compared with CONV were
      0.0003 and 0.0014, respectively. In the hot mass, these methods showed almost the
      same profile curves, although the peak value of X4 was only -1.95% less than that
      of CONV. Although the result of spatial resolution of X4 was slightly degraded,
      image quality and physical performance were good. Therefore, the X4 mashed mode
      used with angular compression was considered clinically useful.

PMID- 15159668
TI  - [Studies on digital watermark embedding intensity against image processing and
      image deterioration].
AB  - In order to apply digital watermarking to medical imaging, it is required to find
      a trade-off between strength of watermark embedding and deterioration of image
      quality. In this study, watermarks were embedded in 4 types of modality images to
      determine the correlation among the watermarking strength, robustness against
      image processing, and image deterioration due to embedding. The results
      demonstrated that watermarks which were embedded by the least significant bit
      insertion method became unable to be detected and recognized on image processing
      even if the watermarks were embedded with such strength that could cause image
      deterioration. On the other hand, watermarks embedded by the Discrete Cosine
      Transform were clearly detected and recognized even after image processing
      regardless of the embedding strength. The maximum level of embedding strength
      that will not affect diagnosis differed depending on the type of modality. It is
      expected that embedding the patient information together with the facility
      information as watermarks will help maintain the patient information, prevent mix
      ups of the images, and identify the test performing facilities. The concurrent
      use of watermarking less resistant to image processing makes it possible to
      detect whether any image processing has been performed or not.

PMID- 15159669
TI  - [Study of improvement in X-ray computed tomography images with a radiation
      treatment planning system: image noise and slice thickness].
AB  - In radiotherapy, dose distribution and calculation of dose monitor units (DMU)
      are generally performed by a radiation treatment planning system using CT images.
      Therefore, differences in calculation can arise as a result of the quality of the
      CT image data. The quality of CT images involves contrast resolution, resolution,
      noise, slice thickness, and other factors. Among these factors, we examined noise
      and slice thicknesses. Results demonstrated that, even if noise increased, CT
      value did not change, and, therefore, did not influence DMU. Examination of slice
      thickness showed that, when the radiation field was rectangular, it was not
      influenced by slice thickness. However, when a multi-leaf collimator (MLC) was
      used, if slice thickness was thicker than the size of the MLC, a difference arose
      in the position of the MLC, and, therefore, some difference arose in dose.
      Therefore, slice thickness should be thinner than the size of the MLC.

PMID- 15159670
TI  - [Grouping of observer's visual characteristics on the basis of difference in the
      criteria of visual detection and selection of the fittest clustering
      method:verification of observer's group with radiologist-like visual
      characteristics].
AB  - Various clustering methods are used in cluster analyses, with each clustering
      method demonstrating unique advantages. Therefore, it is important to make the
      best use of the advantages each method provides. We have recognized that it is
      necessary in the evaluation of X-ray images to classify observers quantitatively
      according to visual characteristics (grouping of observers) and have clustered
      observers using the UPGMA method, which is one of the clustering methods. We
      found that the observers were clustered into two different groups, one with
      radiologist-like characteristics and the other with medical physicist-like
      characteristics. Furthermore, we suggested that the group with radiologist-like
      characteristics was suitable for QC of X-ray images. However, it is doubtful
      whether the UPGMA method is most suitable for the grouping of observers. In this
      work we clustered observers using various clustering methods and examined the
      most suitable method for the evaluation of X-ray images. The results showed that
      the ward method was least suitable for the grouping of observers, and they were
      distinctly grouped into two different categories by using a further method.

PMID- 15159671
TI  - [Consideration of the newly standardized interventional reference point].
AB  - The interventional reference point is standardized by the International
      Electrotechnical Commission (IEC), and is adapted to adult cardiovascular
      studies. We examined the precision of the indicated incident dose at the
      interventional reference point. As a fundamental examination, we compared
      entrance phantom dose and incident dose at the interventional reference point. We
      also compared the entrance skin dose of patients with incident dose at the
      interventional reference point and evaluated the possibility of clinical
      application. Results showed that the incident dose at the interventional
      reference point indicated an underestimation of 0.77 times to an overestimation
      of 2.2 times when representing entrance surface dose. In clinical application,
      the incident dose at the interventional reference point calculated from the dose
      area product tended to overestimate by about 1.17 times the entrance skin dose
      measured by thermoluminescence dosimeter (TLD). Furthermore, the evaluation
      varied according to the angles of the C-arm of the x-ray system. A interventional
      reference point is a useful standard for simple, real-time dose measurement by
      the indirect method. It is important to understand the characteristics of the
      indicated incident dose at the interventional reference point in clinical use.

PMID- 15159672
TI  - [Study of optimal imaging parameters for digitally reconstructed radiographs
      (DRR) in radiotherapy treatment planning using single-slice helical CT].
AB  - In recent years, by making digitally reconstructed radiographs (DRR) from helical
      CT images in the position check of an irradiation field, the verification
      performed by DRR, lineacgraphy (LG), or an electronic portal imaging device
      (EPID) has become possible. We examined the optimal parameters of single-slice
      helical scanning in DRR image construction and the usefulness of DRR replaced
      with the simulation film. We performed a section sensitivity profile at the Z
      axis (SSPz) as evaluation of a physical characteristic of helical CT equipment
      and the form of image of DRR, fixed quantity evaluation of imaging distortion,
      and visual verification of images. It was determined that DRR was influenced by
      the partial volume effect depending on slice thickness and pitch, such that this
      influence occurred when slice thickness and pitch were large. Between a
      simulation film and DRR reconstructed using imaging parameters with a slice
      thickness of 3 mm, pitch of 1.0, and reconstruction slice thickness of 3 mm,
      coincidence was not complete. However, the distortion of DRR was small and the
      difference was not statistically; thus it was considered to be useful. In
      conclusion, we consider that DRR reconstructed using the parameters of single
      slice helical scanning is useful for clinical evaluation in radiotherapy
      planning.

PMID- 15159673
TI  - [An automated slice-matching technique for plain and contrast-enhanced images of
      liver in CT examination by using template matching technique].

PMID- 15159675
TI  - The promise of advances in the field of endocannabinoids.

PMID- 15159677
TI  - Pharmacology of cannabinoids.
AB  - Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the
      pharmacological effects caused by the use of cannabis, is an agonist to both the
      CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription
      in several countries. The non-psychotropic cannabidiol (CBD), some analogues of
      natural cannabinoids and their metabolites, antagonists at the cannabinoid
      receptors and modulators of the endogenous cannabinoid system are also promising
      candidates for clinical research and therapeutic uses. Cannabinoid receptors are
      distributed in the central nervous system and many peripheral tissues including
      spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine
      glands, arteries and heart. Five endogenous cannabinoids have been detected so
      far, of whom anandamide and 2-arachidonylglycerol are best characterized. There
      is evidence that besides the two cannabinoid receptor subtypes cloned so far
      additional cannabinoid receptor subtypes and vanilloid receptors are involved in
      the complex physiological functions of the cannabinoid system that include motor
      coordination, memory procession, control of appetite, pain modulation and
      neuroprotection. Strategies to modulate their activity include inhibition of re
      uptake into cells and inhibition of their degradation to increase concentration
      and duration of action. Properties of cannabinoids that might be of therapeutic
      use include analgesia, muscle relaxation, immunosuppression, anti-inflammation,
      anti-allergic effects, sedation, improvement of mood, stimulation of appetite,
      anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection
      and antineoplastic effects.

PMID- 15159678
TI  - The endocannabinoid-CB receptor system: Importance for development and in
      pediatric disease.
AB  - Endogenous cannabinoids (endocannabinoids) and their cannabinoid CB1 and CB2
      receptors, are present from the early stages of gestation and play a number of
      vital roles for the developing organism. Although most of these data are
      collected from animal studies, a role for cannabinoid receptors in the developing
      human brain has been suggested, based on the detection of "atypically"
      distributed CB1 receptors in several neural pathways of the fetal brain. In
      addition, a role for the endocannabinoid system for the human infant is likely,
      since the endocannabinoid 2-arachidonoyl glycerol has been detected in human
      milk. Animal research indicates that the Endocannabinoid-CB1 Receptor ('ECBR')
      system fulfills a number of roles in the developing organism: 1. embryonal
      implantation (requires a temporary and localized reduction in anandamide); 2. in
      neural development (by the transient presence of CB1 receptors in white matter
      areas of the nervous system); 3. as a neuroprotectant (anandamide protects the
      developing brain from trauma-induced neuronal loss); 4. in the initiation of
      suckling in the newborn (where activation of the CB1 receptors in the neonatal
      brain is critical for survival). 5. In addition, subtle but definite deficiencies
      have been described in memory, motor and addictive behaviors and in higher
      cognitive ('executive') function in the human offspring as result of prenatal
      exposure to marihuana. Therefore, the endocanabinoid-CB1 receptor system may play
      a role in the development of structures which control these functions, including
      the nigrostriatal pathway and the prefrontal cortex. From the multitude of roles
      of the endocannabinoids and their receptors in the developing organism, there are
      two distinct stages of development, during which proper functioning of the
      endocannabinoid system seems to be critical for survival: embryonal implantation
      and neonatal milk sucking. We propose that a dysfunctional Endocannabinoid-CB1
      Receptor system in infants with growth failure resulting from an inability to
      ingest food, may resolve the enigma of "non-organic failure-to-thrive" (NOFTT).
      Developmental observations suggest further that CB1 receptors develop only
      gradually during the postnatal period, which correlates with an insensitivity to
      the psychoactive effects of cannabinoid treatment in the young organism.
      Therefore, it is suggested that children may respond positively to medicinal
      applications of cannabinoids without undesirable central effects. Excellent
      clinical results have previously been reported in pediatric oncology and in case
      studies of children with severe neurological disease or brain trauma. We suggest
      cannabinoid treatment for children or young adults with cystic fibrosis in order
      to achieve an improvement of their health condition including improved food
      intake and reduced inflammatory exacerbations.

PMID- 15159679
TI  - Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic
      benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and
      other treatment-resistant conditions?
AB  - OBJECTIVES: This study examines the concept of clinical endocannabinoid
      deficiency (CECD), and the prospect that it could underlie the pathophysiology of
      migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions
      alleviated by clinical cannabis. METHODS: Available literature was reviewed, and
      literature searches pursued via the National Library of Medicine database and
      other resources. RESULTS: Migraine has numerous relationships to endocannabinoid
      function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors
      supporting therapeutic efficacy in acute and preventive migraine treatment.
      Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects.
      AEA is tonically active in the periaqueductal gray matter, a migraine generator.
      THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is
      now conceived as a central sensitization state with secondary hyperalgesia.
      Cannabinoids have similarly demonstrated the ability to block spinal, peripheral
      and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS
      and related disorders. The past and potential clinical utility of cannabis-based
      medicines in their treatment is discussed, as are further suggestions for
      experimental investigation of CECD via CSF examination and neuro-imaging.
      CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common
      clinical, biochemical and pathophysiological patterns that suggest an underlying
      clinical endocannabinoid deficiency that may be suitably treated with cannabinoid
      medicines.

PMID- 15159680
TI  - On the application of cannabis in paediatrics and epileptology.
AB  - An initial report on the therapeutic application of delta 9-THC (THC)
      (Dronabinol, Marinol) in 8 children resp. adolescents suffering from the
      following conditions, is given: neurodegenerative disease, mitochondriopathy,
      posthypoxic state, epilepsy, posttraumatic reaction. THC effected reduced
      spasticity, improved dystonia, increased initiative (with low dose), increased
      interest in the surroundings, and anticonvulsive action. The doses ranged from
      0.04 to 0.12 mg/kg body weight a day. The medication was given as an oily
      solution orally in 7 patients, via percutaneous gastroenterostomy tube in one
      patient. At higher doses disinhibition and increased restlessness were observed.
      In several cases treatment was discontinued and in none of them discontinuing
      resulted in any problems. The possibility that THC-induced effects on ion
      channels and transmitters may explain its therapeutic activity seen in epileptic
      patients is discussed.

PMID- 15159681
TI  - Cannabinoid agonists in the treatment of blepharospasm--a case report study.
AB  - The benign essential blepharospasm is a subliminal form of primary torsion
      dystonia with still uncertain aetiology. It is characterized by involuntary
      convulsive muscle contractions of the M. orbicularis occuli, accompanied by
      unbearable pain of the cornea, eye bulb and the muscle itself. It has been
      suggested that blepharospasm is neurobiologically based on a dysfunction of the
      basal ganglia and an impairment of the dopamine neurotransmitter system.
      Therefore, therapy of blepharospasm contains administration of anticholinergic-
      and tranquillizing drugs as well as botulinum toxin as neuromuscular blocking
      agent. However serious side effects can be observed as well as failure of
      therapy. In the brain a dense co-localisation of cannabinoid (CB1) and dopamine
      (D2)-receptor was identified which had been associated with the influence of
      cannabinoids on the dopaminergic reward system. Additionally, it has been
      demonstrated that cannabinoids may have an impact on the central GABAergic and
      glutaminergic transmitter system and thus might be involved in the influence of
      movement control. In the present case we administered the cannabinoid receptor
      agonist Dronabinol (Delta-9-Tetrahydrocannabinol) to a woman suffering from
      severe blepharospasm. Multiple treatments with botulinum toxin did not reveal a
      long-lasting beneficial effect. By contrast, treatment with 25 mg Dronabinol for
      several weeks improved the patients' social life and attenuated pain perception
      remarkably. This case study demonstrates that the therapy with a cannabinoid
      agonist may provide a novel tool in the treatment of blepharospasm and maybe of
      other multifactorial related movement disorders.

PMID- 15159683
TI  - Pregnant women: Moire contourgraph and it's semiautomatic and automatic
      evaluation. Dedicated to Professor Antonin Dolezal on his 75th birthday
      anniversary.
AB  - THE AIM OF THE STUDY: Methods of automatic and semiautomatic picture
      determination, evaluation of Moire contourgraph applied to pregnant women TYPE OF
      THE STUDY: Development of algorithm, experimental biomechanical study of the
      dynamics of pregnant women's axial system. METHOD: Achieving the correct data for
      3D picture analysis derived from 2D pictures requires further precision making.
      In general, it requires algorithmization and elaboration of software plug-in,
      which make processing of enormous number of picture data significantly faster.
      The following corrections, adjustments and calculations had to be done to be used
      for Moire contourgraph: correction of the radial distortion of the lens-
      automatically, aligning the histogram--automatically, picture detection of the
      defined object shape and determining its centre of gravity with sub-pixel
      precision--automatically, centre of gravity of the picture of the cross-section
      of pseudo-contour line of the Moire contourgraph--semi-automatically, correction
      of radial shifts in 2D-data orthonormalization--semi-automatically, determining
      the distance of a projected point in 2D from the net as z-coordinate in 3D--semi
      automatically, a) points projected in 2D picture on the pseudo-contour line, b)
      points not projected in 2D picture on the pseudo-contour line. RESULTS:
      Algorithmization of each approach leading to semi-automatic and automatic
      processing of data obtained from Moire contourgraphs. Main distortions, errors
      and inaccuracy of picture data are eliminated. The resulting position of the
      detected point in 3D derived from the 2D picture is determined with sub-pixel
      precision of primary picture coordinates. CONCLUSION: Precision given to
      coordinates of reference points obtained from original picture data allows for
      eliminating limiting inaccuracy in determining real coordinates of a 3D object
      from 2D Moire contourgraph. Coordinates of a virtual model of a real object
      corresponding to its real values are determined. This makes the base for non
      invasive recording and reconstruction of data on the human body's shape including
      the details in 3D. The presented file of methods will be used to assess dynamics
      of the women's axial system during their pregnancy and one year after giving
      birth.

PMID- 15159682
TI  - Professor Antonin Dolezal, MUDr., DrSc.--an outstanding Prague obstetrician. The
      75th birthday anniversary (* January 20, 1929).

PMID- 15159684
TI  - Immunocytes modulate ganglionic nitric oxide release which later affects their
      activity level.
AB  - Pedal ganglia excised and maintained in culture for up to 2 h, release NO at low
      levels. The range can vary between 0 to 1.1 nM. Non-stimulated immunocytes do not
      significantly stimulate ganglionic NO release when incubated with pedal ganglia.
      However, ganglia exposed to immunocytes that had been previously activated by a
      30 min incubation with interleukin 1 beta, release NO significantly above basal
      levels. In these experiments, 91 +/- 2.5% of the non-stimulated immunocytes
      exhibited form factors in the 0.72 to 0.89 range (sampled prior to ganglionic
      addition), whereas 62 +/- 10.3% of the interleukin 1 beta stimulated immunocytes
      had form factors in the 0.39 to 0.49 range, demonstrating activation. Addition of
      the nitric oxide synthase inhibitor, L-NAME (10(-4) M), inhibited basal
      ganglionic NO release as well as that initiated by exposing the ganglia to
      activated immunocytes. Interestingly, non activated immunocytes, following
      ganglionic exposure, exhibited activity levels in the 13% range, representing a
      non significant increase. Cells exposed to interleukin 1 beta had a 65% activity
      level at the beginning of the experiment, followed by a drop of activity to 19 +/
      3.2% after ganglionic exposure. Repeating this last observation in the presence
      of L-NAME (10(-4) M), brought the activity level of the immunocytes back to the
      pre-ganglionic exposure level of activity, demonstrating that ganglionic NO was
      involved in down regulating immunocyte activity.

PMID- 15159685
TI  - Blood serum changes in patients with pain during bone fractures and acute
      pancreatitis.
AB  - OBJECTIVES: Our aim was to evaluate whether some biochemical parameters in the
      blood serum can establish and discriminate pain intensity of different etiology.
      METHODS: Three groups of patients hospitalised at the Department of Surgery have
      been investigated: 1) the patients without pain but with the indicated surgical
      treatment, 2) the patients with acute pancreatitis, which represents severe pain
      of the visceral type, and 3) the patients with fractures of upper or lower
      extremities, which represented acute somatic pain. Whole serum proteins, albumin,
      C-reactive protein, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol,
      triacylglyceroles (triglycerides), apolipoprotein-B and electrophoretic levels of
      alpha-lipoprotein, beta-lipoprotein and pre-beta-lipoprotein were analysed
      immediately after the first clinical inspection in the hospital and then 30 days
      after treatment. RESULTS: The intensity of pain estimated by the visual analogue
      scale (VAS) was higher in patients with acute pancreatitis than in patients with
      fractures. In both diagnoses during persisting pain, the products of lipid
      metabolism such as triacylglyceroles and HDL-cholesterol were enhanced together
      with glucose levels. Electrophoretic measurements, revealed higher levels of beta
      lipoproteins in fractures, and increased values of pre-beta-lipoproteins and
      alpha-lipoproteins in both groups of patients suffering from pain. After 30 days
      of treatment some indicators decreased, but when compared with normal values,
      they were still higher, especially in patients with pancreatitis (HDL
      cholesterol, triacylglyceroles, pre-beta-lipoprotein). In control patients
      without pain symptoms, an increase of LDL cholesterol, triacylglyceroles and beta
      lipoprotein were observed during their stay in hospital, which may be considered
      to be due to hospitalisation stress per se. Acute stress generally influences
      glucose levels so that their increase cannot be considered as a specific marker
      of pain intensity. CONCLUSIONS: It may be concluded from our investigation, that
      the biochemical composition of the blood serum is changing during painful states,
      although the question still remains open to what extent these changes reflect the
      pain intensity and to what extent they may modulate the perception of pain.

PMID- 15159687
TI  - Effect of fasting during the month of Ramadan on serum levels of luteinizing
      hormone and testosterone in people living in the below sea level environment in
      the Jordan Valley.
AB  - OBJECTIVES: To study a possible effect of Ramadan fasting on luteinizing hormone
      and testosterone in people of the Jordan Valley. METHODS: A comparative study
      (n=40) of serum levels of luteinizing hormone (LH) and testosterone (T) between
      people living in the Jordan Valley (JV), n=20, 360 meters below sea level, and
      those living in Ramtha City (RC), n=20, 600 meters above sea level, was conducted
      in December, 1998. A similar study (n=40) was also done during January 1999 in
      fasting people during the month of Ramadan. RESULTS: Serum levels of LH in non
      fasting people of the JV were statistically similar to those in people of RC.
      There was also no difference in serum levels of T between non-fasting people of
      the JV and those in RC. Serum levels of LH in fasting people of the JV were
      statistically indifferent from those fasting in RC. Serum T levels in fasting
      people of the JV, on the other hand, were higher than those in fasting people of
      RC (76+/-18.3 ng/ml compared to 62.7+/-24.2 ng/ml). CONCLUSIONS: It is probably
      the environmental factors such as the higher barometric pressure of the JV
      compared to that at above sea level that play a role in higher serum levels of T
      in people of the JV. Other factors, such as genetic background and/or the
      cultural and nutritional characteristics of the people of the JV, may also
      contribute to this difference in serum T levels.

PMID- 15159686
TI  - Melatonin effects on Schiff's base levels induced by iodide administration in
      rats.
AB  - OBJECTIVES: Administration of iodides to animals, living in iodine-deficient
      areas, can induce necrosis and fibrosis of the thyroid gland. It is believed that
      structural and functional changes of the thyroid may be related to oxidative
      processes. Increased lipid peroxidation levels were reported in murine thyroid
      glands after high doses of iodine. Melatonin (MEL) is believed to exert its
      effects via electron donation to directly detoxify free radicals, such as, e.g.,
      the highly toxic hydroxyl radical. In numerous reports related to the
      antioxidative action of MEL, the authors have considered the protective ability
      of this hormone against peroxidation of lipids. The goal of the study was to
      evaluate oxidative processes and the protective role of MEL in three organs of
      the rat (the liver, the brain, and the lungs) during treatment with different
      doses of iodide. MATERIAL AND METHODS: Schiff's bases (SB) concentrations (a
      parameter of oxidative stress) were measured in liver, lung and brain homogenates
      of male Wistar rats. The animals received iodides in their diet in the following
      concentrations, for 2 weeks: Group 1--Controls (standard normal-iodine diet,
      containing approx. 0.7 mg of kalium iodide per kg; KI/kg); Group 2--diet
      containing 0,25 mg KI/kg; Group 3--diet with 4,0 mg KI/kg; Group 4--diet with 8,0
      mg KI/kg. Group 5--standard normal-iodine diet and MEL alone in a dose of 1 mg/kg
      BW i.p. at 3.00 pm, every day for two weeks. Subsequent three groups (6-8)
      received KI in their diet in doses as above, respectively, together with MEL.
      RESULTS: We noted increased levels of SB in the lungs and in the liver, when
      compared to those observed in controls. We also found decreased SB concentrations
      in liver and lung homogenates after an administration of MEL but--unexpectedly-
      the level of SB increased in the group with the highest dose of iodine in diet in
      lung homogenates. Increased levels of Schiff's bases suggest that iodine is
      involved in oxidative processes not only in the thyroid but also in other
      tissues, and MEL protects against the iodine-induced oxidative stress.
      CONCLUSION: Our results confirm the differences in lipid peroxidation among the
      examined organs. These alterations can possibly be related to different
      sensitivity rates of examined tissues to oxidative damage.

PMID- 15159688
TI  - Impaired somatostatin accumulation within the median eminence in mice with mosaic
      mutation.
AB  - OBJECTIVES: The mosaic mutation (Atp7a(mo-ms)) linked to X-chromosome is caused
      by changes in the Atp7a gene encoding CPx-type protein responsible for the ATP
      dependent copper transport across cell membranes. Mosaic mutant males represent
      an animal model for Menkes disease in humans. Starting from the eighth day of
      life the mosaic males exhibit a progressive decrease in body weight with poor
      viability and progressive paresis of the hind limbs. In order to examine whether
      hypothalamic somatostatin metabolism may be different in normal and copper
      deficient mice, somatostatin accumulation at the level of median eminence in 14
      days old normal and mosaic mutant males was compared. METHODS: An electron
      microscopic immunocytochemical study on ultrathin brain slices was performed
      according to post-embedding immunogold procedure. RESULTS: In non-mutant animals
      somatostatin has been detected in many synapses within median eminence. Gold
      particles moderately decorated synaptic vesicles and mitochondria. In mosaic
      mutant animals somatostatin expression within the median eminence was very low
      and only a few gold particles represented somatostatin. Particles were
      sporadically associated with synaptic vesicles, mitochondria or cytoskeleton
      elements. Moreover, pre- and post- synaptic parts of synapses were very often
      swollen. CONCLUSION: Our data demonstrating that copper deficiency leads to the
      pathological changes within the median eminence ultrastructure and severe
      impairment of somatostatin expression suggest that this trace metal is an
      important element necessary for normal neurohormonal brain development.

PMID- 15159689
TI  - Insulin-induced changes of proteolytic activity of the lysosomal enzymes.
AB  - OBJECTIVES: Changes in the activity of alanine aminopeptidase, leucine
      aminopeptidase and cathepsins D and L in the liver and kidney of male and female
      of mice, injected with 0.4 IU/kg b.w. insulin for 4 and 8 days. METHODS: The
      homogenates of the liver and kidney were taken for examination. The activity of
      alanine aminopeptidase, leucine aminopeptidase and cathepsins D and L has been
      determined according to [1] method. RESULTS: The activity of alanine
      aminopeptidase, leucine aminopeptidase, cathepsins D and L in the liver and
      kidney of male and female of mice decreased in effect of insulin injections for 4
      and 8 days. CONCLUSION: The changes of enzyme activities showed a stimulating
      effect of the insulin injection on the labilization of lysosomal membranes. The
      range of the reaction remained in a relationship with the kind of the organ, the
      type of enzyme, time over which insulin introduced operates in the organism, and
      with the sex.

PMID- 15159690
TI  - Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene
      expression in mouse heart by microarray.
AB  - OBJECTIVES: Aging is associated with significant alterations in gene expression
      in numerous organs and tissues. Anti-aging therapy with peptide bioregulators
      holds much promise for the correction of age-associated changes, making a
      screening for their molecular targets in tissues an important question of modern
      gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was obtained
      by directed synthesis based on amino acid analysis of natural brain cortex
      peptide preparation Cortexin. In humans, Cortagen demonstrated a pronounced
      therapeutic effect upon the structural and functional posttraumatic recovery of
      peripheral nerve tissue. Importantly, other effects were also observed in
      cardiovascular and cerebrovascular parameters. DESIGN: Based on these latter
      observations, we hypothesized that acute course of Cortagen treatment, large
      scale transcriptome analysis, and identification of transcripts with altered
      expression in heart would facilitate our understanding of the mechanisms
      responsible for this peptide biological effects. We therefore analyzed the
      expression of 15,247 transcripts in the heart of female 6-months CBA mice
      receiving injections of Cortagen for 5 consecutive days was studied by cDNA
      microarrays. RESULTS: Comparative analysis of cDNA microarray hybridisation with
      heart samples from control and experimental group revealed 234 clones (1,53% of
      the total number of clones) with significant changes of expression that matched
      110 known genes belonging to various functional categories. Maximum up- and down
      regulation was +5.42 and -2.86, respectively. CONCLUSION: Intercomparison of
      changes in cardiac expression profile induced by synthetic peptides (Cortagen,
      Vilon, Epitalon) and pineal peptide hormone melatonin revealed both common and
      specific effects of Cortagen upon gene expression in heart.

PMID- 15159691
TI  - Spontaneous ovarian adenocarcinoma in the domestic turkey breeder hen (Meleagris
      gallopavo): effects of photoperiod and melatonin.
AB  - OBJECTIVES: The effect of photoperiod or melatonin treatments on ovarian
      adenocarcinoma in turkey breeder hens (Meleagris gallopavo) was investigated to
      evaluate the usefulness of this animal as a model for studying ovarian cancer.
      METHODS: In Experiment 1, photoperiod effects were tested by exposing turkeys
      with ovarian tumors to 8 wks of short days (8:16LD) followed by a 12 wk period of
      long days (16:8LD). In Experiment 2, exogenous melatonin was administered to
      turkeys during long day-induced development of ovarian tumors. In both
      experiments, the stage of tumor growth was scored weekly on a scale of 0 to 4.
      RESULTS: It was clear that exposure to short days produced complete regression of
      tumors, with a mean time to score 0 of 4.4 wks. Following re-exposure to a long
      photoperiod, all of the same birds showed re-growth of the ovarian tumor with a
      mean time to first palpable detection of 5.4 wks. When melatonin was administered
      daily during the long photoperiod (Experiment 2), there was a significant delay
      in the re-growth of tumors. CONCLUSION: It was clear from this study that the
      growth of solid ovarian tumors in the turkey breeder hen was promoted by long
      photoperiods and ceased, to the point of remission, on short photoperiods. Thus,
      ovarian adenocarcinoma in turkeys can be completely manipulated by photoperiod.
      In addition, treatment with melatonin attenuates tumor growth in the turkey hen.
      The results suggest that the domestic turkey hen is a useful in vivo model for
      studying spontaneous ovarian adenocarcinoma.

PMID- 15159692
TI  - Light and electron microscopic examination of pineal gland in rats exposed to
      constant light and constant darkness.
AB  - OBJECTIVE: This study was aimed to examine the pineal gland of rats exposed to
      constant light and darkness at light and electron microscopic level. DESIGN: For
      this purpose 18 male Wistar rats were used. Animals were divided into three
      groups. Rats in group I (Control) were kept under 12 hrs light: 12 hrs dark
      conditions. Rats in group II were exposed to constant darkness, while rats in
      group III were exposed to constant light for 6 weeks. At the end of the
      experiment, all animals were killed by decapitation. The pineal glands of rats
      were removed, then processed for light and electron microscopy. RESULTS: In our
      study, extensive number of pinealocytes was observed in the structure of pineal
      gland of rats exposed to constant darkness and some of the observed pinealocytes
      were determined to contain double nucleoli. Furthermore, mitochondria and lipid
      droplets in the cytoplasm of pinealocytes were increased and rough endoplasmic
      reticulum sacs were enlarged in this group. Whereas, in rats those exposed to the
      constant light, a decrease in pinealocyte intensity was associated with increase
      in the connective tissue between parenchymal cells. Additionally, mitochondria
      and lipid droplets in the cytoplasm of cells were decreased. CONCLUSIONS: It was
      observed that the pinealocyte cell activity of rats exposed to constant darkness
      was increased but decreased in rats exposed to constant light.

PMID- 15159694
TI  - Possible effects of melatonin on thymus gland after pinealectomy in rats.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of
      pinealectomy and pinealectomy plus melatonin administration on thymus weight and
      histology in adult Wistar-albino rats. METHODS: The animals were divided into
      three groups. Group I and Group II were designated as control (sham
      pinealectomized) and pinealectomized rats, respectively. They received 10%
      ethanol (0.1 ml per day s.c.) alone. The rats in Group III were pinealectomized
      and daily injected with melatonin (3 mg/kg/0.1 ml 10% ethanol per day s.c.)
      commencing on the day seven after surgical operation. Injections were applied for
      two months. RESULTS: The thymus atrophied and its weight decreased after
      pinealectomy (p<0.001). The cortico-medullary boundary could not be distinguished
      and in the thymus induced a loss of lymphoid elements, increased number of
      phagocytic macrophages and enlarged blood vessels. Melatonin prevented the thymic
      involution. CONCLUSIONS: These results suggest that pinealectomy decreases thymus
      weight and that long-term administration of melatonin restores thymus weight to
      normal levels.

PMID- 15159693
TI  - Evaluation of subretinal fluid absorption by optical coherence tomography in
      circumscribed choroidal hemangioma after photodynamic therapy with Verteporfin.
AB  - PURPOSE: To determine if optical coherence tomography (OCT) measurements of
      retinal thickness at the fixation point (RTFP) can be used to confirm the
      effectiveness of photodynamic therapy (PDT) with verteporfin in the treatment of
      symptomatic circumscribed choroidal hemangioma (CCH). METHODS: Nine eyes of nine
      patients with subretinal fluid under foveal centre were treated by PDT with a
      dose of 6 mg/m2 of intravenous verteporfin administered 5 minutes before a laser
      irradiation at 689 nm. Visual outcomes, initial, and final findings were
      evaluated using biomicroscopy, OCT, ultrasound, fluorescein angiography, and
      indocyanine green angiography. RESULTS: After a mean follow-up of 8 months
      (range, 3-18 months) OCT showed absorption of subretinal fluid in all cases
      (100%). Maximal decrease of RTFP was seen within first month after treatment.
      Average RTFP decreased from 378 microm (range, 221 microm-849 microm)
      preoperatively to 190 microm (range, 118 microm-321 microm) postoperatively
      (p=0.017, paired t-test). Mean best corrected visual acuity (BCVA) improved from
      4/16 (range, 4/5-1/20) preoperatively to 4/8 (range, 4/3-1/15) postoperatively
      (p=0.0046, paired t-test). An improvement in BCVA was observed in all cases
      (100%, one to seven lines on Early Treatment Diabetic Retinopathy Study charts).
      BCVA returned to 4/5 or better in six patients (67%). Mean tumor height decreased
      from 3.2 mm (range, 1.5 mm-4.0 mm) preoperatively to 0.9 mm (range, 0 mm-2.4 mm)
      postoperatively (p=0.00003, paired t-test). There was no measurable tumor height
      in four cases (44%), there were marked reduction in the other five cases (56%) on
      ultrasound. CONCLUSIONS: OCT appears to be useful method for evaluation of
      subretinal fluid absorption after the treatment of CCH by PDT with verteporfin.
      RTFP value can be used for quantification of subretinal fluid under the foveal
      centre. Functional results of PDT with verteporfin in CCH are limited in pre
      existing retinal alterations. Randomised trial with single versus repeated
      sessions of PDT with verteporfin is needed.

PMID- 15159695
TI  - Glucocorticoid-dependency of increased adiposity in a model of hypothalamic
      obesity.
AB  - It is known that rats treated, at neonatal age, with monosodium L-glutamate (MSG)
      develop neuroendocrine and metabolic abnormalities, resulting in a phenotype of
      hypothalamic obesity, characterized by increased adiposity, corticosteronemia and
      leptinemia. OBJECTIVE: We explored whether adrenal manipulations could result in
      the reversion of this phenotype of hypothalamic obesity. EXPERIMENTAL DESIGNS:
      Newborn male rats, treated with MSG or vehicle (CTR), were submitted to sham
      operation, bilateral adrenalectomy (ADX) or bilateral adrenal enucleation (AE) on
      day 120 of age. Animals were examined 21 days after ADX, combined or not with
      corticosterone (B) substitution (ADX+B), and on days 21 and 35 after AE. Food
      intake, body weight and body fat mass were monitored; additionally circulating
      levels of insulin, leptin, ACTH and B were measured. RESULTS: Our data indicate
      that: a) normalization of basal B circulating levels in, 21 day-ADX and -AE, MSG
      rats fully reversed hyperinsulinemia, hyperleptinemia and significantly decreased
      body fat mass; and b) recovery of hypercorticosteronemia in, 35 day-AE, MSG rats
      fully restored this phenotype of hypothalamic obesity. CONCLUSION: Our study
      strongly supports that high glucocorticoid production is the main factor
      responsible for the development of enhanced adiposity in MSG rats and,
      importantly, that this abnormality could be reversed by an appropriate therapy.

PMID- 15159696
TI  - Qualitative and quantitative studies on the ultrastructure of ovine pinealocytes
      during postnatal development.
AB  - OBJECTIVE: The study was performed to analyze the ultrastructure of ovine
      pinealocytes during the period of postnatal development. MATERIAL AND METHODS:
      The pineals of newborn, 10-week and one-year old females of the domestic sheep
      were prepared for ultrastructural investigations. The point count analysis was
      used in quantitative studies of the pinealocyte substructures. RESULTS: The
      prominent feature of pinealocytes in the newborns was the presence of well
      developed rough endoplasmic reticulum and numerous polysomes. The pinealocyte
      cytoplasm contained also smooth endoplasmic reticulum, mitochondria, Golgi
      apparatus, lysosomes, dense core vesicles, multivesicular bodies and lipid
      droplets. Pinealocytes of the 10-week and 1-year old sheep were characterized by
      the occurrence of numerous vesicles and short cisterns of smooth endoplasmic
      reticulum, abundant microtubules and lipid droplets. Pinealocytes of the adult
      sheep were distinguished by well developed Golgi apparatus, numerous dense core
      vesicles and multivesicular bodies. The relative volume of rough endoplasmic
      reticulum in pinealocytes was significantly higher in the newborn sheep than in
      two other groups. The relative volume of mitochondria was significantly higher in
      pinealocytes of the 10-week old sheep than the newborns and one-year old animals.
      The relative volume of Golgi apparatus was significantly higher in the one-year
      old animals than in two other groups. No differences concern lysosomes. The
      relative volume of lipid droplets as well as the numerical density of dense core
      vesicles and multivesicular bodies increased significantly with age. CONCLUSION:
      The ultrastructure of ovine pinealocytes undergoes the marked changes during
      postnatal development. The changes concern mainly substructures involved in
      secretory activity.

PMID- 15159697
TI  - Impact of a switch from typical to atypical antipsychotic drugs on quality of
      life and gonadal hormones in male patients with schizophrenia.
AB  - OBJECTIVES: We investigated the effects of a switch from typical to atypical
      antipsychotic drugs (olanzapine, n=8; perospirone, n=9; or quetiapine, n=13) on
      quality of life and hypothalamo-pituitary-gonadal axis hormones. METHODS: The
      subjects were 30 male chronic schizophrenia inpatients. The assessment was done
      before and after the switch. RESULTS: After the switch, (i) scores of the Brief
      Psychiatric Rating Scale total and three factors (anxiety-depression, anergia,
      and thought disturbance) decreased, (ii) the overall severity score of the Drug
      Induced Extra-Pyramidal Symptoms Scale tended to decrease, (iii) prolactin
      decreased but gonadal hormones remained unchanged, and (iv) scores on all three
      subscales (psychosocial, motivation/energy, and symptoms/side effects) in the
      Japanese version of the Schizophrenia Quality of Life Scale (JSQLS) decreased.
      However, there were no significant group effects, or time-by-group interactions.
      In addition, score changes from baseline in psychosocial and motivation/energy
      subscales in the JSQLS were correlated with those in psychotic symptoms,
      particularly in the anxiety-depression factor. Moreover, responders had been
      taking lower doses of typical antipsychotic drugs, and had higher serum estradiol
      concentrations than non-responders before the switch. CONCLUSIONS: The study
      indicated that the switch to atypical antipsychotic drugs was effective in
      reducing elevated prolactin without affecting the gonadal hormones and in
      improving quality of life patients who had been treated with typical
      antipsychotic drugs.

PMID- 15159698
TI  - Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm
      following aneurysmal SAH.
AB  - Cytokines play a key role in mutual influence of the immunological, endocrine and
      CNS systems. It has been proven that proinflammatory ILs may intensify the
      cascade of biochemical changes in ischemic brain damage. Vasospasm, which may
      accompany SAH and often coexists with symptoms of DINDs, is the cause of ischemic
      changes in the brain. It is thought that immunological mechanisms may be one of
      the causes of degenerative-productive changes in vessel walls, in delayed
      vasospasm following SAH, which lead to substantial vasospasm and in consequence
      too cerebral ischemia. In the randomly selected group of patients, who underwent
      surgical treatment after aneurysmal SAH, we determined the concentration of IL-1
      beta and IL-6 in CSF in the periods between Days 0 to 3; 4 to 7; and 8 to 15
      after the occurrence of SAH. The presence and dynamics of development of
      vasospasm were assessed on the basis of increasing DINDs as well as CT and
      cerebral angiography. We examined the concentrations of ILs in CSF using
      radioimmunological methods, applying commercially available tests for their
      assessment. We found that in the period between 8 and 15 days after SAH, in
      increasing delayed vasospasm and DINDs, here is a statistically significant
      increase concentration of IL-1 beta in CSF (105.4 +/- 46.9 pg x ml-1; p<0.005),
      and no significant changes in patients without vasospasm and neurological
      deficits. On the other hand, we noted a statistically significant increase
      concentration of IL-6 in CSF (4802 +/- 1170 ng x ml-1; p<0.05) only in the acute
      phase after SAH (Days 0-3) in patients in poor clinical condition, in whom
      delayed vasospasm and cerebral ischemia developed later. This increase of ILs
      level in CSF is probably related to the intensity of the SAH, and secondarily
      aggravates the vasospasm and ischemic changes in the brain.

PMID- 15159699
TI  - How much tachycardia in infants can be attributed to fever?
AB  - STUDY OBJECTIVES: We evaluate the hypothesis that pulse rate increases linearly
      with increased body temperature in infants and determine how much tachycardia in
      infants can be explained by a 1 degrees C (1.8 degrees F) increase in body
      temperature. METHODS: Infants younger than 1 year and presenting to a pediatric
      emergency department were prospectively enrolled. Rectal temperature and pulse
      rate were measured. Research personnel rated behavioral state as sleeping, awake
      and quiet, fussy, or crying. Patients were excluded if they were fussy or crying
      or if they had any medical condition expected to cause tachycardia. The remaining
      patients were divided into 6 age-based groups. Linear regression analysis of
      pulse rate and temperature was performed for each group. RESULTS: Four hundred
      ninety patients were enrolled. Pulse rate increased linearly with temperature in
      all age groups older than 2 months (adjusted r2=0.102 to 0.376) but not in
      infants younger than 2 months (adjusted r2=0.004). In infants aged 2 months or
      older, a multivariate linear regression model adjusted for age showed that pulse
      rate increased an average of 9.6 beats/min (95% confidence interval 7.7 to 11.5)
      per 1 degrees C (1.8 degrees F) increase in temperature (adjusted r2=0.225). At
      any given temperature, the prediction interval for an individual's pulse rate had
      a span of approximately 64 beats/min. CONCLUSION: In infants 2 to 12 months of
      age, pulse rate increases linearly with body temperature, with a mean increase of
      9.6 beats/min for each 1 degrees C (1.8 degrees F) increase in body temperature.
      Pulse rates of individual infants vary greatly, however, with a broad range of
      pulse rates observed at any given temperature.

PMID- 15159700
TI  - Do children require hospitalization after immediate posttraumatic seizures?
AB  - STUDY OBJECTIVE: We determine whether children with immediate posttraumatic
      seizures require hospitalization for observation of possible neurologic
      complications. METHODS: This was a prospective observational cohort study of
      children younger than 18 years with blunt head trauma resulting in immediate
      posttraumatic seizures. Patients were examined by faculty emergency physicians
      and underwent cranial computed tomography (CT) scanning. Children were divided
      into 2 cohorts according to the presence or absence of traumatic brain injury on
      cranial CT scan, with the a priori assumption that children with posttraumatic
      seizures who have abnormal cranial CT scan results require hospitalization. The
      outcomes of interest were neurologic complications (including further seizure
      activity or neurologic deficits) or the necessity for neurosurgical intervention.
      Medical records of hospitalized patients were reviewed, and patients discharged
      from the emergency department (ED) were contacted by telephone approximately 1
      week after hospital discharge to identify those who developed short-term
      neurologic complications. RESULTS: Sixty-three children with a median age of 7
      years (interquartile range 3 to 14 years) had posttraumatic seizures, and all but
      1 child underwent cranial CT imaging. Ten (16%; 95% confidence interval [CI] 8%
      to 27%) patients had traumatic brain injuries on CT scan, and all were
      hospitalized. Three of these 10 patients underwent craniotomy, and 2 patients had
      further seizure activity. Fifty-two patients had normal cranial CT scan results,
      and 20 patients were hospitalized for observation. Telephone follow-up was
      obtained in 31 of the 32 patients with normal CT scan results who were discharged
      from the ED. None of the 52 patients (0%; 95% CI 0% to 5.6%) with normal cranial
      CT scan results had further seizure activity or required neurosurgical
      interventions. CONCLUSION: Children with normal neurologic examination results
      and normal cranial CT scan results after immediate posttraumatic seizures are at
      low risk for further short-term complications that require immediate
      hospitalization. These children may be considered for discharge home from the ED.

PMID- 15159701
TI  - Apparent life-threatening events in infants: high risk in the out-of-hospital
      environment.
AB  - STUDY OBJECTIVE: The purpose of this study is to define the prevalence and
      significance of apparent life-threatening events among infants in the out-of
      hospital setting. METHODS: This was a retrospective, cohort, outcome study of
      infants for whom a caregiver activated the emergency medical services (EMS)
      system. For purposes of the study, an apparent life-threatening event was defined
      as an episode of apnea, skin color change, or change in muscle tone. Study data
      characteristics included initial physical appearance, work of breathing,
      circulation skin signs, pulse rate, respiratory rate, and overall concern for the
      chief complaint as interpreted by EMS personnel. RESULTS: Sixty (7.5%) of 804
      infants encountered by EMS during the study period met our criteria for apparent
      life-threatening event. Mean age was 3.1+/-3.3 months, and 55% were boys. Of the
      infants with apparent life-threatening event, 50 (83.3%) infants appeared to be
      in no distress, 8 (13.3%) infants were in mild distress, and 2 (3.3%) infants
      were in moderate distress. General physical appearance, work of breathing,
      circulatory signs, respiratory rate, and pulse rate were not clinically abnormal
      in the study group as a whole. Critical conditions associated with apparent life
      threatening event included pneumonia or bronchiolitis (12%), seizure (8%), sepsis
      (7%), intracranial hemorrhage (3%), bacterial meningitis (2%), dehydration (2%),
      and severe anemia (2%). Limitations of the study included retrospective design
      and inability to follow up study patients beyond hospital discharge. CONCLUSION:
      An apparent life-threatening event in an infant can present without signs of
      acute illness and is commonly encountered in the EMS setting. It is often
      associated with significant medical conditions, and EMS personnel should be aware
      of the clinical importance of an apparent life-threatening event. Infants meeting
      criteria for an apparent life-threatening event should receive a timely and
      thorough medical evaluation.

PMID- 15159702
TI  - Skull radiograph interpretation of children younger than two years: how good are
      pediatric emergency physicians?
AB  - STUDY OBJECTIVE: We determine pediatric emergency physicians' accuracy in
      interpreting skull radiographs of children younger than 2 years and determine the
      characteristics of misidentified skull radiographs. METHODS: A set of 31 skull
      radiographs (16 with fractures, 15 normal) was compiled from children younger
      than 2 years who were evaluated for head trauma in a pediatric emergency
      department from March 3, 1997, to March 3, 1998. A pediatric radiologist
      reinterpreted the films and agreed with all of the original readings in the final
      set. Participants (attending level physicians) were asked to identify the
      presence, location, and pattern of any fracture. Skull radiograph interpretation
      was considered radiographically correct if the presence, location, and pattern of
      fracture were correctly identified and was considered diagnostically correct if
      the presence of a fracture was recognized. RESULTS: Twenty-five of 26 eligible
      pediatric emergency physicians completed the study. The mean of each
      participant's radiographically correct interpretation was 65%+/-10% (mean+/-SD),
      and diagnostically correct interpretation was 80%+/-9%. The group's mean
      sensitivity for diagnostically correct interpretation was 76%+/-15%, and
      specificity was 84%+/-14%. Shorter fractures were identified correctly less often
      (63% < or =5 cm versus 93% >5 cm; mean difference 30%; 95% confidence interval
      21% to 39%). Diagnostically correct rates did not differ according to age of
      patient, physician practice location, years in practice, or practice in ordering
      skull radiographs. CONCLUSION: Pediatric emergency physicians have limited
      accuracy in interpreting skull radiographs of children younger than 2 years.
      Shorter fractures are more commonly misinterpreted.

PMID- 15159703
TI  - The epidemiology of case fatality rates for suicide in the northeast.
AB  - STUDY OBJECTIVE: We examine how method-specific case fatality rates for suicide
      differ by age and sex. METHODS: Seven northeastern states provided mortality and
      hospital discharge data (1996 to 2000). Suicide acts were divided into 8
      categories according to the method used. For each method, the fraction of acts
      resulting in death (the method-specific case fatality rate) was calculated. Only
      suicide acts that resulted in hospitalization or death were included. RESULTS:
      Overall, 13% of all suicide acts proved lethal (23% for males compared with 5%
      for females; 7% for people aged 15 to 24 years compared with 34% for individuals
      aged > or =65 years). Poisoning with drugs accounted for 74% of acts but only 14%
      of fatalities; firearms and hanging accounted for only 10% of acts but 67% of
      fatalities. Firearms were the most lethal means (91% resulted in death), followed
      by drowning (84%) and hanging (82%). For every means, method-specific case
      fatality rates were higher for male victims and older individuals. Age and sex
      were associated with overall case fatality rates primarily because of their
      association with the distribution of methods chosen. CONCLUSION: Our findings are
      based on suicide acts that result in hospitalization or death and therefore
      underestimate the actual incidence of suicide acts and overestimate case fatality
      rates. Nevertheless, we find that age and sex influence overall case fatality
      rates primarily through their association with methods used, rather than because
      of variation in method-specific case fatality rates.

PMID- 15159704
TI  - Suicidal patients in the emergency department: Who is at greatest risk?

PMID- 15159706
TI  - Treating gun violence before the 911 call.

PMID- 15159705
TI  - The life cycle of crime guns: a description based on guns recovered from young
      people in California.
AB  - STUDY OBJECTIVE: We describe the life cycle of crime guns recovered from young
      people-the movement of those guns from manufacture to criminal use-and identify
      associations between the characteristics of those guns and their possessors,
      purchasers, sellers, and places of origin. METHODS: This is a cross-sectional
      study of data from gun ownership tracing records compiled by the Bureau of
      Alcohol, Tobacco, Firearms and Explosives for 2,121 crime guns recovered in
      California from persons younger than 25 years and traced in 1999. Purchaser and
      seller data for handguns were updated when possible by linking to California
      handgun sales records. RESULTS: The 2,121 traced guns were recovered from 1,717
      young people. Guns recovered from persons aged 21 to 24 years were most
      frequently also purchased by persons aged 21 to 24 years; those recovered from
      persons younger than 18 years were most often purchased by persons aged 45 years
      or older. Small-caliber handguns made up 41.0% of handguns recovered from persons
      younger than 18 years but 25.2% of handguns recovered from persons aged 21 to 24
      years. The median time from sale to recovery (commonly called time to crime) for
      all guns was 6.4 years (interquartile range 2.7 to 12.4 years). A time to crime
      of less than 3 years, suggesting deliberate gun trafficking, was observed for
      17.3% of guns recovered from persons younger than 18 years but 34.6% of guns
      recovered from persons aged 21 to 24 years. Ten retailers who sold 10 or more
      traced guns accounted for 13.1% of all guns traced to a retailer. Handguns whose
      purchaser and possessor were the same person were more likely than others to be
      large-caliber semiautomatic pistols (29.3% and 11.7%, respectively); their median
      time to crime was 0.2 years (69 days). CONCLUSION: Analysis of crime-gun
      ownership traces reveals patterns that may help refine gun violence prevention
      efforts and render them more effective.

PMID- 15159707
TI  - Physician's guide to assessing and counseling older drivers.

PMID- 15159708
TI  - Commentary: The role of the emergency physician in older driver safety.

PMID- 15159709
TI  - Communicating life-threatening diagnoses to patients in the emergency department.
AB  - Disclosing a new, life-threatening diagnosis to a patient is difficult for the
      physician, the patient, and the family. The disclosure provokes a wide range of
      reactions from both the patient and family, to which the emergency physician must
      respond. This interaction is further complicated by the limited time the
      emergency physician can spend with the patient, the strained resources of a busy
      emergency department (ED), and, oftentimes, the inability to make a definitive
      diagnosis based on the ED workup and evaluation. We present a case seen recently
      in the ED in which a new, life-threatening illness requires disclosure. We offer
      guidelines for the emergency physician that emphasize patient- and family
      centered disclosure of the worrisome diagnostic findings. Additionally, we
      discuss the essential roles of other allied health professionals in addressing
      the patient's nonmedical concerns (eg, health insurance, social issues) and in
      creating a smooth transition for the patient from the ED to further inpatient or
      outpatient care.

PMID- 15159710
TI  - Integrating the Accreditation Council for Graduate Medical Education Core
      competencies into the model of the clinical practice of emergency medicine.
AB  - In response to public pressure for greater accountability from the medical
      profession, a transformation is occurring in the approach to medical education
      and assessment of physician competency. Over the past 5 years, the Accreditation
      Council for Graduate Medical Education (ACGME) has implemented the Outcomes and
      General Competencies projects to better ensure that physicians are appropriately
      trained in the knowledge and skills of their specialties. Concurrently, the
      American Board of Medical Specialties, including the American Board of Emergency
      Medicine (ABEM), has embraced the competency concept. The core competencies have
      been integral in ABEM's development of Emergency Medicine Continuous
      Certification and the development of the Model of Clinical Practice of Emergency
      Medicine (Model). ABEM has used the Model as a significant part of its blueprint
      for the written and oral certification examinations in emergency medicine and is
      fully supportive of the effort to more fully define and integrate the ACGME core
      competencies into training emergency medicine specialists. To incorporate these
      competencies into our specialty, an Emergency Medicine Competency Taskforce
      (Taskforce) was formed by the Residency Review Committee-Emergency Medicine to
      determine how these general competencies fit in the Model. This article
      represents a consensus of the Taskforce with the input of multiple organizations
      in emergency medicine. It provides a framework for organizations such as the
      Council of Emergency Medicine Residency Directors (CORD) and the Society for
      Academic Emergency Medicine to develop a curriculum in emergency medicine and
      program requirement revisions by the Residency Review Committee-Emergency
      Medicine. In this report, we describe the approach taken by the Taskforce to
      integrate the ACGME core competencies into the Model. Ultimately, as competency
      based assessment is implemented in emergency medicine training, program
      directors, governing bodies such as the ACGME, and individual patients can be
      assured that physicians are competent in emergency medicine.

PMID- 15159711
TI  - The emergency department community-acquired pneumonia trial: Methodology of a
      quality improvement intervention.
AB  - Community-acquired pneumonia causes more than 4 million episodes of illness each
      year and has high morbidity, mortality, and total cost of care. Nationwide,
      nearly 75% of community-acquired pneumonia patients are initially evaluated and
      treated in hospital-based emergency departments (EDs). Substantial variation
      exists in illness severity assessment, hospital admission decisions, and
      performance of recommended processes of care. We designed an ED-based quality
      improvement trial focused on the initial care of patients with community-acquired
      pneumonia. We used the Pneumonia Severity Index and level of arterial oxygenation
      to identify patients at low risk for 30-day mortality and to guide admission
      decisionmaking. We assessed the performance of recommended "best practices,"
      consisting of assessment of arterial oxygenation, the collection of blood
      cultures for inpatients, and the timely initiation of appropriate empiric
      antibiotic therapy for inpatients and outpatients. We conducted a 32-site,
      cluster-randomized trial in Pennsylvania and Connecticut, comparing the
      effectiveness and safety of 3 guideline implementation strategies of increasing
      intensity. The multifaceted implementation plans were carried out in conjunction
      with each state's quality improvement organization. This article describes the
      background, objectives, and methodology of this trial to translate evidence-based
      knowledge on the quality and efficiency of care for community-acquired pneumonia
      into clinical practice.

PMID- 15159712
TI  - Images in emergency medicine. Generalized vaccinia.

PMID- 15159714
TI  - [Apoptosis and hibernation of cardiomyocytes of periscar zone as factor of
      chronic cardiac aneurysm progression].
AB  - Tissue specimen from chronic aneurysms and adjacent myocardium obtained at
      aneurysmectomy and coronary bypass surgery from 46 patients were subjected to
      morphological study. Immunohistochemical methods and electronic microscopy were
      applied for detection of apoptosis and hibernation of cardiomyocytes in 11 cases
      and histochemical determination of activity of energetic enzymes succinate and
      lactate dehydrogenase was used in 5 cases. Cardiomyocytes from peri and intra
      scar layers of myocardium were found to be in a state of hibernation while some
      of them were in a state of apoptosis. Extent of apoptosis was different in
      aneurysms on different stages of organization. Number of altered cardiomyocytes
      was the greatest in immature aneurysms. Basing on these findings apoptosis of
      hibernating cardiomyocytes was suggested to be one of factors of expansion of
      sclerotic zone and aneurysm formation.

PMID- 15159713
TI  - The implantable cardioverter defibrillator: technology, indications, and impact
      on cardiovascular survival.
AB  - Since the introduction of the implantable cardioverter defibrillator (ICD) for
      the management of patients with high risk of arrhythmic SCD, there has been
      increasing use of this device. Its basic promise to effectively terminate
      ventricular tachycardia (VT)-ventricular fibrillation (VF) has been repeatedly
      met. In several randomized trials, the ICD has been shown to be superior to
      conventional anti-arrhythmic therapy, both in patients with documented VT-VF
      (secondary prevention) and those with high risk such as left ventricular ejection
      fraction and no prior sustained VT-VF (primary prevention). In both groups, the
      ICD showed overall and cardiac mortality reduction. The device now can more
      accurately detect VT-VF and differentiate these from other arrhythmias through a
      series of algorithms and direct-chamber sensing. Therapy options include painless
      antitachycardia pacing, low-energy cardioversion, and high-energy defibrillation.
      The technique implant is now simple as a pacemaker with one lead attached to an
      active (hot) can functioning as the other electrode. Among other improvements is
      its weight, volume, multiprogrammability, and storage of information,dual-chamber
      pacing and sensing, dual-chamber defibrillation, and addition of biventricular
      pacing for cardiac synchronization. It is anticipated that further improvement in
      ICD technology will take place and the list of indications will grow.

PMID- 15159715
TI  - [Clinical value of morphological analysis of radial and internal mammary arteries
      in patients with ischemic heart disease].
AB  - Morphological study of intraoperative biopsies of radial and internal mammary
      arteries taken from patients with ischemic heart disease during coronary bypass
      surgery revealed structural alterations of intima and media mostly in radial
      artery. These alterations depended on severity of arterial hypertension, presence
      of diabetes and extent of atherosclerosis. Hyperplasia of intima could be a basis
      for radial artery spasm and cause of graft stenoses and occlusions. Therefore
      protocols of pre and post operative care should take into consideration
      individual risk factors and morphological and functional features of an artery
      used for grafting.

PMID- 15159716
TI  - [Prognosis of unstable angina resulting from restenosis after percutaneous
      angioplasty of saphenous vein grafts].
AB  - AIM: To assess frequency of unstable angina due to restenosis after percutaneous
      angioplasty of venous grafts and to elucidate risk factors of its development.
      MATERIAL AND METHODS: Percutaneous interventions were successfully performed in
      100 out of 106 patients with venous graft stenoses. These patients were followed
      up for 17+/-11 (maximum 36) months. RESULTS: Unstable angina due to venous graft
      restenosis developed in 24% of patients. Patients with unstable angina compared
      with those without were characterized by higher frequency of hyperlipidemia (83
      vs. 51%, respectively, p=0.032), lower rate of stenting (46 and 72%,
      respectively, p=0.032), greater residual stenosis (15+/-13 and 9+/-8%,
      respectively, p=0.008). At multifactorial regression analysis the following
      factors were significant predictors of unstable angina: hyperlipidemia (odds
      ratio [OR] 3.55, 95% confidence interval [CI] 1.64-8.39), and residual stenosis
      after intervention (OR 1.04, 95% CI 1.01-1.07, p=0.04). In a subgroup of patients
      with hyperlipidemia there was a tendency to greater rate of unstable angina among
      patients not taking statins compared with users of statin (50 and 29%,
      respectively, p=0.083). CONCLUSION: Unstable angina developed in (1/4) of
      patients after balloon dilatation of venous grafts and hyperlipidemia was its
      most powerful predictor.

PMID- 15159717
TI  - [Effect of long-term physical training on hemostasis in patients with coronary
      heart disease and non-insulin dependent diabetes].
AB  - AIM: To study effects of 6-month physical training on some parameters of
      hemostasis in patients with coronary heart disease and non-insulin dependent
      diabetes (NIDDM). RESULTS: Long-term physical training resulted in lowering of
      fibrinogen level and increase of fibrinolytic activity assessed as euglobulin
      fraction clot lysis time, while factor VII activity remained unchanged. These
      changes were accompanied with elevation of total and high density lipoprotein
      cholesterol levels without any shifts in low density lipoprotein cholesterol and
      triglycerides. Most pronounced positive effect physical training exerted on
      results of a test with standard single fat load, which was used as a model of
      postprandial lipemia. Serum cortisol level significantly decreased after 6-month
      training, especially after fat load and subsequent physical exertion. CONCLUSION:
      In patients with combination of coronary heart disease and NIDDM long-term
      physical training was associated with decreased thrombogenicity of blood.

PMID- 15159718
TI  - [The treatment of coronary atherosclerosis: effect of the use of stents on
      immediate and long term results of coronary angioplasty].
AB  - Immediate and long term results of 2 methods of coronary angioplasty (balloon
      dilatation and stenting) were analyzed retrospectively. During 10 years
      proportion of stent implantations increased 30-fold reaching 95-97% of coronary
      interventions. This was associated with improvement of immediate results of
      angioplasty: lowered rates of myocardial infarctions, urgent coronary artery
      bypass graftings and acute coronary artery occlusions (from 2.7% after balloon
      angioplasty to 0.6% after stenting). Improved long-term prognosis after stenting
      manifested in lower frequency of cardiovascular events. Five year survival was
      98,8 and 92.7% after stenting and balloon angioplasty, respectively (p=0.004).
      However effect of stenting on rates of angiographic restenosis and repeat
      revascularizations was less pronounced (27.1 and 30.4%, respectively, after
      stenting vs. 30.1 and 34.5%, respectively, after balloon angioplasty).

PMID- 15159719
TI  - [Clinical assessment of immediate results of various methods of myocardial
      revascularization in ischemic heart disease patients with isolated anterior
      descending coronary artery disease].
AB  - Open heart coronary artery bypass grafting (CABG), minimally invasive coronary
      artery surgery, transluminal balloon coronary angioplasty (TBCA) and coronary
      stenting were carried out in 25, 35, 12 and 38 patients with isolated anterior
      descending coronary artery disease, respectively. In immediate period after
      procedures there were 2 deaths (among patients subjected to open heart CABG and
      TBCA) and 2 nonfatal myocardial infarctions (among patients treated with TBCA and
      stenting). In 2 patients repeat interventions were performed during initial
      hospitalization (in 1 after TBCA and in 1 after stenting). Exercise tolerance
      increased by 40+/-8, 44+/-7, 45+/-8, 53+/-9 W in patients treated with open heart
      CABG, minimally invasive surgery, TBCA and stenting, respectively. Thus surgical
      and endovascular methods of treatment of patients with isolated anterior
      descending coronary artery lesions produced beneficial clinical effect and were
      associated with relatively low rate of postoperative complications.

PMID- 15159720
TI  - [Relation between resistance to oxidation and cholesterol acceptance of high
      density lipoproteins in patients with ischemic heart disease].
AB  - Cholesterol (CH) acceptance ability of high density lipoproteins (HDL) was
      assessed in 43 ischemic heart disease (IHD) patients, including patients with
      post-infarction cardiosclerosis and class II-III effort angina. CH acceptance
      ability of HDL was measured as increment of HDL CH after incubation with
      artificial CH-containing system. Oxidabilities of HDL and total plasma were
      estimated by quantitation of lipid peroxidation products (hydroperoxides and
      thiobarbituric acid-reactive substances - TBARS) after incubation with Cu(2+)
      ions. HDL fraction (after apo B lipoproteins removal) of IHD patients appeared to
      include 2 times less additive CH compared with donor's HDL despite lower (-12%)
      HDL CH level. Negative correlation (r =-0.38, p<0.05) existed between formed
      TBARS in HDL and HDL CH acceptance. In total plasma of IHD patients elevation of
      both formed TBARS and particularly hydroperoxides was observed. Parallelism
      between decrease of CH acceptance by HDL, oxidability of HDL and of total plasma
      testifies on weakness not only of CH-accepting, but also of antioxidant HDL
      functions in IHD patients.

PMID- 15159721
TI  - [Comparative assessment of efficacy of tissue plasminogen activator and
      streptokinase in the treatment of patients with acute myocardial infarction].
AB  - AIM: To compare results of treatment of patients with acute myocardial infarction
      with tissue plasminogen activator (TPA) and streptokinase. MATERIAL AND METHODS:
      TPA (100 mg intravenously) and streptokinase (1500000 U intravenously) were used
      for thrombolytic therapy of acute myocardial infarction in 114 and 118 patients,
      respectively. RESULTS: TPA treated compared with streptokinase treated patients
      were characterized by less frequent serious cardiac rhythm and conduction
      disturbances and hypotension during thrombolysis (p<0.05), as well as less
      frequent pathological Q-waves formation (p<0.001). More than 50% lowering of
      initially elevated ST-segment by 90-th minute occurred more often in TPA treated
      patients (p<0.001). Differences between TPA and streptokinase treated patients in
      mortality (3.5 and 7.6%, respectively), reinfarction rate during first 24 hours
      (3.5 and 5.1%, respectively), aneurysm formation (9.1 and 14.7%, respectively),
      and heart failure development (4.5 and 11.0%, respectively) were not significant.
      CONCLUSION: The use of TPA for thrombolytic therapy of patients with acute
      myocardial infarction gave better results than the use of streptokinase.

PMID- 15159722
TI  - [Clinical Efficacy of Combination Therapy With Trimetazidine and Angiotensin
      Converting Enzyme Inhibitors in Patients With Hypertension and Ischemic Heart
      Disease Associated With Type II Diabetes].
AB  - AIM: To assess in a randomized open study effect of 12-15 week use of angiotensin
      converting enzyme inhibitors (ACEI) with and without trimetazidine on myocardial
      perfusion reserve in patients with ischemic heart disease (IHD) and/or
      hypertension associated with type II diabetes. MATERIAL: Patients (n=69)
      receiving long term ACEI therapy with transient myocardial perfusion defects
      during dipyridamole stress test. METHODS: Control patients (n=29, including 15
      with IHD) continued to receive an ACEI, while in trimetazidine group (n=40,
      including 21 IHD patients) trimetazidine (60 mg/day) was added to ACEI. Single
      photon emission computer tomography with (199)Thallium Chloride was used for
      measurement of myocardial perfusion reserve. Changes of physical working
      capacity, intracardiac hemodynamics and glycemia were studied only in
      trimetazidine group. RESULTS AND CONCLUSION: Significant 52% (mean) decrease
      (32.5% in IHD patients) of perfusion defects and acceleration on total clearance
      of Tl-199 were registered in trimetazidine group while no considerable changes of
      myocardial perfusion were revealed in control group. Most substantial changes of
      myocardial blood flow reserve occurred in patients with moderate alterations of
      left ventricular diastolic filling, and among IHD patients - in those without
      cardiac dilatation and pronounced diastolic left ventricular dysfunction.
      Significant increase (45.9 and 23.9% in patients with and without IHD,
      respectively) of total work performed during bicycle exercise was registered in
      trimetazidine treated patients. In IHD patients decline of initially elevated
      intramyocardial tension was also observed.

PMID- 15159724
TI  - [The use of nebivolol for the treatment of hypertension in patients with
      osteoarthrosis].
AB  - Nebivolol (5 mg/day) was given for 3 months to 20 patients with essential
      hypertension and osteoarthrosis treated with diclofenac and to 20 other patients
      with essential hypertension. After 3 months lowering of blood pressure, decreases
      of components of 24-hour blood pressure profile, improvements of signs of left
      ventricular hypertrophy occurred in both groups. There were no significant
      differences between changes of parameters studied between 2 groups. Thus
      diclofenac (nonselective cyclooxygenase inhibitor) did not attenuate
      antihypertensive effect of nebivolol and its action on left ventricular
      hypertrophy.

PMID- 15159723
TI  - [Effect of fixed low dose combination of perindopril and indapamide on processes
      of cardiovascular remodeling in previously untreated patients with hypertension].
AB  - AIM: To assess changes of blood pressure (BP) and processes of cardiovascular
      remodeling during treatment of previously untreated patients with hypertension
      with fixed low dose combination of perindopril and indapamide. MATERIAL: Patients
      with untreated hypertension (n=30, mean age 46.7+/-1.8 years, 16 men, 14 women)
      received low-dose perindopril (2 mg) - indapamide (0.625 mg) combination for 6
      months. METHODS: Twenty four-hour BP monitoring, measurement of left ventricular
      (LV) mass index and wall and interventricular septal thickness, carotid artery
      intima-media thickness, pulse wave velocity and cerebral blood flow velocity.
      RESULTS: Target BP level was reached in 83.3% of patients. BP monitoring revealed
      significant lowering of daytime and nocturnal systolic BP (-13.2%, p<0.0001 and 
      14.5%, p<0.0001, respectively), daytime and nocturnal diastolic BP (- 14.3%,
      p<0.0001 and -15.3%, p<0.0001, respectively). Significant reduction of LV mass
      index (-12%, p=0.0002) was also observed. Both LV posterior wall and
      interventricular septal thicknesses were reduced as well (-5.1%, p<0,01). This
      was accompanied by decreases of intima-media thickness of right and left carotid
      arteries (-5,4%, p=0.04 and -5,3%, p=0.01, respectively), reduction of stiffness
      of elastic arteries (carotid-femoral pulse wave velocity decreased by 8%,
      p=0.003), and increase of cerebral blood flow velocity. CONCLUSION: The use of
      perindopril/indapamide combination in hypertensive patients was associated BP
      lowering and positive effects on remodeling both of the heart and large and
      medium arteries.

PMID- 15159725
TI  - [Effect of programmed hemodialysis on parameters of ventricular repolarization
      and cardiac rhythm disturbances in patients with terminal renal failure].
AB  - Programmed hemodialysis was associated with alterations of the process of
      ventricular myocardium repolarization, prolongation of noncorrected and corrected
      QT and JT intervals, and increase of their dispersion. This augmented
      heterogeneity of repolarization was found to be interrelated with development of
      dangerous cardiac rhythm disturbances, and changes of plasma concentrations of
      electrolytes.

PMID- 15159726
TI  - [Comparison of QT-Interval Measurement Techniques and Their Clinical Value].
AB  - Long QT-interval is one of most important predictors of risk of development of
      life threatening arrhythmias and sudden death. Correct measurement of QT-interval
      is essential for diagnosis of its prolongation. At present the Bazett formula for
      calculation of corrected QT (QT(c) = QT/ radical (RR)) is a standard method of QT
      estimation. However historically in Russia calculation of predicted QT (QT(k) = k
      radical (RR)) QT(k) has become an accepted technique. Furthermore many authors in
      this country apply criteria created for QT(c) for interpretation of QT(k) values.
      This results in hyperdiagnosis of QT prolongation in unaffected persons,
      erroneous conclusions on harmless nature of this condition, and underestimation
      of risk in patients with real long QT syndrome. Thus it is vital to proclaim
      calculation of QT(c) an obligatory standard and to use existing international
      criteria for its interpretation.

PMID- 15159727
TI  - [Pathogenesis, clinical picture, and diagnosis of myopericarditides].
AB  - Basing on own data and literature survey the authors analyze clinical course of
      viral myopericarditides. Special emphasis is made on evolution of
      electrocardiographical signs in which four stages are distinguished. It is noted
      that incidence of hemorrhagic myopericarditides probably of viral nature is
      increasing. The paper contains recommendations on treatment of patients with
      myopericarditis. The disease has favorable prognosis. However prognosis of
      diffuse myopericarditis remains unfavorable and its rational treatment -
      insufficiently established.

PMID- 15159728
TI  - [Stroke and Other Thromboembolic Complications of Atrial Fibrillation. Part II.
      Prevention With Warfarin].
AB  - In part II of a series of papers on epidemiology and drug prevention of stroke
      and other thromboembolic complications of atrial fibrillation the authors present
      data on clinical pharmacology of oral anticoagulants as well as discussion of
      results of randomized studies demonstrating high efficacy of warfarin in primary
      and secondary prevention of thromboembolism. According to cumulative data of 7
      randomized trials average stroke risk lowering in patients with atrial
      fibrillation associated with the use of warfarin is 62%. Total bleeding rates
      during treatment with oral anticoagulants fluctuate between 5 and 10%; about half
      of these bleedings are serious.

PMID- 15159729
TI  - [First experience with "live" three-dimensional echocardiography in Russia].
AB  - Revival of interest to three-dimensional echocardiography during recent years was
      invoked by introduction of essentially novel ultrasound technology of "live"
      three-dimensional imaging. We introduce here the first experience of the use of
      <<live>> three-dimensional echocardiography in Russia comprising examination of
      74 patients with various pathology of the heart. Positions and sections are
      described allowing best visualization of pathology of cardiac valves and other
      intracardiac structures. Our experience shows that at present <<live>> three
      dimensional echocardiography should be considered to be an important supplement
      to standard echocardiography. However in some <<difficult>> cases it can be the
      only non-invasive technique able to provide complete information on the size of
      ventricular and atrial septal defects, valvular and other cardiac pathology.

PMID- 15159730
TI  - [Nosocomial sinusitis in patients with a severe craniocerebral trauma: etiology
      and pathogenesis].
AB  - The article presents a brief review of the literature on the problem of
      nosocomial sinusitis (NS) and the experience with 264 patients with
      craniocerebral trauma in whom NS etiology and pathogenesis were established
      basing on the findings of microbiological, morphological and immunological
      studies. Gram-negative opportunistic microflora appeared to be an underlying
      cause in etiology of NS. Regional microcirculatory disorders due to a severe
      craniocerebral trauma as well as suppression of nonspecific resistance and
      immunity contributed most of all to pathogenesis of the disease. Combination of
      unfavourable etiological and pathogenetic factors in patients with a
      craniocerebral trauma led to development of NS.

PMID- 15159731
TI  - [Immunomorphological features of chronic cystic sinusitis].
AB  - Morphogenesis of cystic lesions of the paranasal sinuses is described.
      Immunohistochemical studies were conducted using a panel of monoclonal and
      polyclonal antibodies. A comparative analysis of the immunohistochemical
      parameters of the cystic lesions suggested the presence of chronic inflammation
      with immune component in the wall of false cysts.

PMID- 15159732
TI  - [Modern characteristics of clinical course and treatment of otogenic purulent
      meningitis].
AB  - A total of 170 patients aged 2.5 to 60 years have received treatment for otogenic
      meningitis caused by acute (n=37, 21.2%) or chronic otitis media (n=137, 78.2%).
      Otogenic meningitis ran atypically with masked clinical manifestations in 32.2%
      patients. It is thought justified to repeat an antibiotic injection into the
      cerebrospinal canal in a severe course of meningitis, especially in combination
      of meningitis with other forms of intracranial complications. If clinical signs
      of acute otitis media and meningitis manifested weakly and, therefore, otogenic
      nature of meningitis is questionable, it is recommended to implement an expectant
      treatment policy. The absence of noticeable positive shifts in the course of the
      disease after several days of intensive conservative treatment is an indication
      for surgical intervention.

PMID- 15159733
TI  - [Experimental and morphological rationale for using bone-matrix transplants in
      defects of nasal bones].
AB  - Experimental and morphological trials on rats and dogs demonstrate distinct
      osteoinductive properties of the bone and embryonal matrix. Dynamics of
      osteogenesis in implantation of the embryonic matrix is accelerated. The results
      of the histological studies confirm value of using bone-matrix materials to speed
      up regenerative processes in the area of nasal bone defect.

PMID- 15159734
TI  - [Allobrephotympanoplasty in chronic otitis media in children].
AB  - An original technique of allobrephotympanoplasty in children with tympanic
      defects is suggested. It uses fetal dura mater as a transplant. The operation was
      made in 8 children. Four patients regained their hearing completely, three
      patients' hearing improved significantly. Long-term follow-up results allowed
      conclusion on good plastic properties of this material and resistance to
      infection. Such brephoplastic material can be recommended for tympanoplasty in
      specialized department as it is simple in storing and is relatively cheap.

PMID- 15159735
TI  - [Prevalence of human papilloma virus types and their influence on the course of
      the disease in children suffering from recurrent respiratory papillomatosis].
AB  - The type of human papilloma virus (HPV) was determined in 26 children aged
      between 1 year 10 months to 15 years 5 months suffering from recurrent
      respiratory papillomatosis (RRP). Polymerase chain reaction identified DNA of HPV
      type 6, 11, 16 and 18. HPV DNA was detected in all the patients including fifteen
      patients infected with HPV type 11; seven patients infected with HPV type 6; four
      children infected with HPV type 6 and 11. Types 16 and 18 of HPV were not
      detected. The analysis of RRP course has found that laryngeal papillomatosis runs
      a more aggressive course in cases with HPV type 11 infection than in those with
      HPV type 6.

PMID- 15159736
TI  - [Maxillary affection in fibrous dysplasia in children].
AB  - The article reviews foreign and domestic literature on the problem of maxillary
      fibrous dysplasia (MFD) and reports 10 cases of disseminated monoosseous MFD in
      children aged 3-14 years treated surgically. The scope of the intervention
      depended on the process location, age of the patients and function-sparing
      principle. All the operations provided satisfactory cosmetic and functional
      effect. Their results advocate an individual approach to choice of the scope and
      kind of surgical intervention.

PMID- 15159737
TI  - [Surgical treatment of acute parapharyngitis].
AB  - A total of 2,690 patients with paratonsillitis (PT) including 83 (3.08%) ones
      with PT complicated by parapharyngitis were treated from 1984-2002. At admission,
      all the patients were punctured, the paratonsillar abscess was opened. Abscess
      tonsillectomy was made in 82 patients. Four patients developed flegmon of the
      neck. Besides abscess tonsillectomy, opening and drainage of cervical flegmon
      were conducted in these patients. Two patients died of mediastinitis. Thus,
      success of treatment of acute parapharyngitis depends on early diagnosis,
      especially at prehospital stage, detailed examination in ENT department, early
      and adequate surgical intervention and combined conservative treatment. It is
      recommended to measure the content of middle mass molecules during the treatment
      of pyoinflammatory, septic conditions in otorhinolaryngological practice.

PMID- 15159738
TI  - [Aspiration cavernosotomy in vascular chronic hypertrophic rhinitis].
AB  - Sparing surgical intervention in the nasal cavity of children with chronic
      hypertrophic rhinitis and normalization of nasal breathing are important targets
      for pediatric rhinosurgeons. The technique of aspiration cavernosotomy in a
      vascular variant of nasal cavity hypertrophy including processes of vascular cut
      and one-stage aspiration of blood from the wound channel and nasal cavity meet
      the requirements of low-invasive surgery and maximally provides the safety of the
      nasal mucosa in the best traditions of submucous vasotomy. The instruments for
      aspiration cavernosotomy, technique of its conduction, surgical treatment results
      in 12 children and adolescents are described.

PMID- 15159739
TI  - [Effects of blood substitutes of different pharmacological groups and the mode of
      their injection on the bloodflow of rats].
AB  - Central and peripheral bloodflow before and after intramuscular and intravenous
      injections of 0.9% NaCl (control groups, n=20) and perfluothane (n=20) in a dose
      of 5 ml/kg was studied in 40 Wistar rats. Dopplerographic study of the bloodflow
      was carried out on a diagnostic device Biomedical AU-5 (Italy). The study showed
      that intramuscular injections of both 0.9% NaCl and perfluothane did not lead to
      a significant increase of the bloodflow, but perfluothane caused a significantly
      greater increase of both arterial and venous bloodflow in the injection zone in
      comparison with the control. Intravenous injection of perfluothane increased
      significantly the systemic and local bloodflow in comparison with the baseline
      level and control, while total peripheral resistance was decreased.

PMID- 15159740
TI  - [The unity of systemic pathogenetic mechanisms in visceral diseases associated
      with generalized periodontitis].
AB  - The authors analyzed published data and their own findings which confirm the
      unity of systemic mechanisms of pathogenesis in combined visceral diseases and
      generalized periodontitis. The data proving the pathogenetic role of free-radical
      oxidation of lipids, proteins, and low-molecular-weight thiols, immunological
      imbalances, and deficiencies of the major macro- and trace elements (Ca, Mg, K,
      Na, Zn, Cu, Fe) are presented. The detected metabolic disorders and homeostatic
      shifts characterize the universal processes mediating alteration of cell
      structures in different organs and tissues in combined diseases.

PMID- 15159741
TI  - [Morphological and cytochemical features of the gingival mucosal epithelium in
      women during different phases of the menstrual cycle].
AB  - Morphological analysis of smears of the gingival epithelium by computer-aided
      morphometry was carried out in women during the secretory and proliferation
      phases of the menstrual cycle. During the secretory phase the cell ratio was
      characterized by higher percentage of epitheliocytes in the terminal stages of
      differentiation. Size of the nuclei and cytoplasm of intermediate cells,
      concentration of total protein in them, number of the nucleolar organizer zones,
      and degree of bacterial contamination of epitheliocytes is higher during the
      secretory phase than during the proliferation phase.

PMID- 15159742
TI  - [Optic coherent tomography in evaluation of the buccal mucosa status.
      Communication 1. Normal mucosa].
AB  - The potentialities of optic coherent tomography (OCT) in the diagnosis of the
      buccal mucosa status were studied and the results are presented in two
      communications. Communication 1 demonstrates the tomograms of various parts of
      normal buccal mucosa and methods of their identification as exemplified by
      analysis of 1180 in vivo and 43 ex vivo OCT images. Using parallel histo
      tomographic comparison, the authors distinguished the main signs of optic images,
      depending on the type of epithelium and characteristic features of the connective
      tissue stroma in various parts of the buccal mucosa. These signs are essential
      for understanding the optic images of the mucosa in disease, which will be shown
      in communication 2.

PMID- 15159743
TI  - [The concept of maintenance therapy for periodontal inflammations characterized
      by an aggressive course].
AB  - Long-term studies have reported significance of supportive periodontal therapy in
      patients with aggressive forms of periodontitis. The success of periodontal care
      depends on a long commitment of both the patient and the dentist. The continuing,
      periodic assessment of periodontal structures aims to determine treatment needs.
      The main aim of supportive periodontal treatment in case of aggressive
      periodontitis is to prevent the recurrence and progression of periodontal
      disease. This paper contains information concerning significance and methods of
      plaque removal by the patient after appropriate periodontal therapy.

PMID- 15159744
TI  - [Thromboresistance of vascular wall endothelium in patients with chronic
      generalized periodontitis and its changes during combined short wave therapy].
AB  - Thromboresistance of endothelial vessels is decreased in patients with chronic
      generalized periodontitis (CGP). The severity and type of thromboresistance
      suppression in the vascular wall depend on the severity of CGP. Combined short
      wave therapy completely or partially (depending on the disease severity) restored
      thromboresistance of endothelial vessels.

PMID- 15159745
TI  - [A new method for treating chronic sialodochitis and sialolithiasis in dilatation
      of the intraglandular portion of the parotid duct].
AB  - A new method for the treatment of chronic sialodochitis and sialolithiasis is
      suggested for cases with essential dilatation of the duct in the intraglandular
      compartment of the parotid gland: the external wall of dilated duct is dissected
      and the two resultant parts are twisted inside and sutured to the internal wall
      of the dilated duct; the parotid duct is ligated at the site of its exit from the
      gland.

PMID- 15159746
TI  - [Clinical picture, diagnosis, and therapy of adenolymphoma of the parotid gland].
AB  - Clinical data on 33 patients with adenolymphoma (AL; Warthin's tumor) of the
      parotid gland are presented, including a case with development of mucoepidermoid
      carcinoma in the presence of AL. Specific features in the clinical course of AL
      are described, which depend on the tumor location, probable suppuration of the
      contents of the cystic cavities, etc. The diagnostic significance of some
      accessory methods of examination is evaluated: ultrasonic method,
      sialoscintigraphy, single-photon emission computer-aided tomography, cytological
      method, etc. High accumulation of (99m)Tc pertechnetate in AL was observed in
      some cases. The ratio of the glandular and lymphoid components in AL, which can
      vary, is clinically significant. The treatment strategy in AL is the same as in
      surgery for pleiomorphic adenoma of the parotid gland.

PMID- 15159747
TI  - [Role of X-ray cephalometric analysis in planning reconstructive interventions in
      patients with combined maxillodental and facial abnormalities].
AB  - A retrospective analysis of case histories of 110 patients subjected to
      reconstructive surgery for occlusion abnormalities was carried out. The data
      indicate that complete correspondence of teleroentgenography to planned treatment
      was observed in only 34.5% cases; this correspondence was partial in 48.3% cases,
      and in 17.2% patients planned treatment did not correspond to the pathogenesis of
      the abnormality at all. The majority of patients in whom the diagnosis was in
      complete disagreement with planned treatment were subjected to maxillary
      osteotomy for mesial occlusion. This choice was based on esthetic preferences of
      the patient and stability of the results.

PMID- 15159748
TI  - [Repair of mandibular defects by dosed distraction. Part I. Distraction of the
      callus for osteoplasty of the mandible by local tissues].
AB  - During the war in Afghanistan the author repaired gunshot defects in the mandible
      using a compression-distraction device (CDD) which he designed in cooperation
      with A. Kh. Shamsudinov. Osteoplasty of the mandible is based on the distraction
      osteogenesis phenomenon. Proceeding from this phenomenon, the author developed
      several variants of mandibular osteoplasty in 1982-1983, one of these variants
      being osteoplasty with local tissues, permitting bloodless repair of mandibular
      defects of up to 5 cm long. Osteoplasty with local tissues can be used not only
      for repair of mandibular defects of any origin, but for enlarging the mandible in
      congenital or acquired abnormalities as well.

PMID- 15159749
TI  - [Changes of the immune status of children with relapsing herpetic stomatitis,
      suffering from allergic diseases, during licopide treatment].
AB  - The efficiency of licopide in combination with traditional treatment was
      evaluated in 59 children aged 1-14 years suffering from allergic diseases and
      relapsing herpetic stomatitis. Immunological studies were carried out before and
      after a course of therapy: local oral immunity, cellular immunity (in the blast
      transformation test with phytohemagglutinin), lymphocyte populations and
      subpopulations, humoral immunity values (IgA, IgM, IgG, and IgE), and C3
      complement component were evaluated. The results indicate that licopide in
      complex with traditional methods normalized the immunological values, had a
      favorable impact on the course of relapsing herpetic stomatitis, and led to a
      stable remission of allergic diseases (p<0.001).

PMID- 15159750
TI  - [Time of permanent teeth eruption in schoolchildren of Saint-Petersburg].
AB  - The terms of permanent teeth eruption were analyzed in 909 children (permanent
      residents of St. Petersburg) aged 7-15 years. The study showed that all groups of
      permanent teeth, except the first molars, erupted on the mandible earlier than on
      the maxilla. In girls only canines and second molars erupted earlier than in
      boys. There was virtually no sex-specific difference in the terms of eruption of
      both premolars, and the terms of the end of eruption of both groups of canines
      were virtually the same in boys and girls. Twenty-one children lacked some of
      permanent teeth by 15 years (the age considered as the upper threshold level for
      the end of normal tooth eruption). The most frequent teeth that failed to erupt
      in time were the upper lateral canines (33.3% of all teeth which failed to erupt
      by the age of 15 years), lower central canines and upper first premolars and
      molars (12.8% each).

PMID- 15159751
TI  - [Dental status of patients with chronic diffuse diseases of the liver].
AB  - The intensity and prevalence of diseases of hard dental tissues and periodontium,
      correlation of serum, unstimulated mixed saliva, and gingival fluid biochemistry,
      and changes in the periodontal microcirculation were studied in 122 patients with
      chronic diffuse diseases of the liver. Specific changes in the biochemical
      parameters of unstimulated mixed saliva and gingival fluid in these patients were
      directly related to the biochemical parameters of the serum and the fact of
      dental treatment. Microcirculatory disorders in the distal portions of
      periodontal vessels (attached gingiva and gingival papilla) depended on local
      factors, while disorders in larger vessels of the buccal mucosa (transitional
      fold) were related to the severity of the underlying disease.

PMID- 15159753
TI  - [Anatomic conditions for isolated proximal resection of the pancreas].
AB  - Based on summarized data of the literature it is concluded that proximal
      resection of the duodenum in chronic pancreatitis with lesion of the pancreatic
      head is possible only bearing in mind variability of arterial blood supply.
      Experience of surgical treatment of 19 patients with chronic pancreatitis who
      underwent isolated resections of pancreatic head due to inflammatory changes of
      pancreas' proximal parts demonstrates expediency of this surgery. Maximal
      resection of pancreatic tissue permits to decrease risk of purulent and
      inflammatory complications and promotes favorable course after surgery.

PMID- 15159752
TI  - [Surgery of cholelithiasis: from past to present].
AB  - Development of surgery of cholelithiasis is regarded. Classic surgical
      interventions on the gall bladder and bile ducts in complicated disease (acute
      cholecistitis, jaundice, cholangitis), postcholecistectomy syndrome, surgical
      trauma of the bile ducts are substantiated. To 1980s modern views on pathogenesis
      of the disease have been formed. However, unresolved problems of surgical policy,
      traumatism of open surgeries in complicated forms of the disease (postoperative
      lethality in acute cholecistitis was 37% and over) made results of treatment
      unsatisfactory. Correction of policy's problems, application of mini-invasive
      procedures, diapeutic approach and precision technique opened up-to-date period
      in surgery of cholelithiasis. It permitted to reduce postoperative lethality in
      acute and chronic course of the disease to 0.08 - 0.1%.

PMID- 15159754
TI  - [Laparoscopy and puncture biopsy in diagnosis of focal lesions of the liver].
AB  - Based on the results of examination of 208 patients with different tumors of the
      liver it is concluded that in the majority of cases it is possible to avoid
      puncture biopsy of the liver and laparoscopy for diagnosis of focal lesion of the
      liver (FLL) before surgery because these invasive procedures don't improve
      efficacy of diagnosis. On the contrary it may lead to complications including
      implantation metastases (3.33%). Correct appliance of modern diagnostic
      algorithms permits to increase efficacy of FLL diagnosis to 82.27% without
      invasive procedures.

PMID- 15159755
TI  - [Radio-frequency ablation appliance in resection of the liver].
AB  - Pilot experience with "Radionics Cool-Tip RF System" appliance for radio
      frequency ablation (RFA) in hepatic resection in the patients with focal lesions
      of the liver is presented. Advantages of RFA as an alternative method for
      hemostasis are demonstrated. With this technique bisegmentectomy (II - III) was
      performed in 4 patients, right-sided hemihepatectomy - in 2 patients. RFA
      permitted to minimize intraoperative blood loss without increase of surgery time.
      There were no severe complications during surgery and in early postoperative
      period. The method permits to perform combined surgeries without a significant
      increase of surgical risk.

PMID- 15159756
TI  - [Diagnosis and treatment of different types of high scar strictures of the
      hepatic ducts].
AB  - Results of treatment of 224 patients with scar strictures of the hepatic ducts
      (BSDH) are presented. Based on Bismuth's classification of BSDH E.I. Galperin
      (2002) proposed own one. According to this classification there were 17 (7,6%)
      patients with type "+2" (stump of common hepatic duct - CHD more than 2 cm), 26
      (11,6%) - with type "+1" (stump of CHD 1 - 2 cm), 72 (32,2%) - with "0" type
      (stump of CHD less than 1 cm), 54 (24,1%) - with "-1" type (upper fornix of CHD
      confluence is not affected), 35 (17,4%) - with "-2" type (CHD confluence is
      destroyed), 20 (8,9%) - with "-3" type (strictures of segmental ducts). There
      were greater number of previous surgeries in the patients with "-1" and "-2"
      types (p<0,05). Jaundice and secondary biliary liver cirrhosis were seen more
      frequently in types "0" - "-3". Hepaticojejunostomy was the surgery of choice.
      For approach to unaltered wall of hepatic ducts (HD) section of lobar ducts in
      types "+1", "0", excision of portal plate and partial resection of IV hepatic
      segment (31 patients) in "-1" - "-3" types were used. Exchangeable transhepatic
      drainage (ETD) was applied in 31 patients due to impossibility to excise scar
      tissues completely. In early postoperative period 9 (4%) patients died due to
      purulent cholangitis (7 patients) and insufficiency of anastomosis (2 patients).
      Long-term results were evaluated in 180 (80,4%) patients from 1 to 14 (6,6+/-3,9)
      years of follow-up. Thirteen surgeries were performed for repeated strictures.
      The main cause of restrictures was inadequate resection of scar tissues and
      unreasonable refusal of ETD (7 patients). Developed surgical technique in
      different types of strictures permits to reduce postoperative lethality and the
      rate of restrictures.

PMID- 15159757
TI  - [Forty-year experience of surgical treatment of generalized myasthenia].
AB  - Forty-year experience with surgical treatment of generalized myasthenia (GM)
      based on 2977 cases is analyzed. Role of special methods of mediastinum
      examination (CT, MRT) is demonstrated, indications to thymectomy are validated.
      It is noted that developed diagnostic algorithm, surgical technique, management
      before and after surgery improved significantly immediate and long-term results.
      Development of clinical, immunological and morphologic criteria of thymectomy
      effect permitted to predict course of GM and to optimize complex therapy after
      surgical treatment.

PMID- 15159758
TI  - [Surgical treatment of hormone-resistant form of nonspecific ulcerative colitis].
AB  - From 1990 to 2002 seventy-nine patients with hormone-resistant form of
      nonspecific ulcerative colitis (NUC) underwent surgery. There were 37 men, 42
      women, mean age was 34.4 +/- 3.8 years. Severe form of NUC was in all the
      patients, total lesion of the colon was in 60.8% cases, subtotal - in 25.3%, and
      right-sided - in 13.9%. Acute disease was seen in 21 (26.6%) patients, chronic
      recurrent - in 42 (53.2%), chronic continuous - in 16 (20.2%). Complex intensive
      treatment including glucocorticoids (prednisolon 2 mg/kg/day) was used in all the
      patients. Criteria of efficacy were clinical, laboratory and instrumental data
      (rate of stool, hemodynamics, hyperthermia, pain syndrome, hemoglobin, level of
      leukocytes and albumin, results of endoscopy and roentgenoscopy). Absence of
      positive results during 3 weeks was regarded as inefficacy of therapy and
      indication for surgery. Subtotal resection of the colon with ileostoma or
      sygmostoma was performed in 68 patients. Detection of resistance to hormones
      before development of NUC's intestinal complications (intestinal bleeding, toxic
      dilatation and perforation of colon) permitted to improve results of surgery:
      number of postoperative complications reduced from 60 to 8 - 9%, lethality - from
      21 to 4.6%.

PMID- 15159759
TI  - [Pathogenesis of recurrences of acute gastroduodenal ulcerous bleedings].
AB  - Based on analysis of morphologic data, oxygen regime and redox potential it is
      demonstrated that progressive ischemic necrosis in periulcerous zone is the basis
      of recurrence of gastroduodenal ulcerous bleedings. Systemic hemostatic therapy,
      antisecretion drugs, endoscopic methods of hemostasis don't guarantee absence of
      bleeding recurrence. Prognosis of recurrence of gastroduodenal ulcerous bleedings
      must be based on evaluation of clinical and endoscopic data. Partial pressure of
      oxygen and redox potential in ulcer's crater are the objective criteria of threat
      of bleeding's recurrence.

PMID- 15159760
TI  - [Dissection and dissected aneurysm of the abdominal aorta].
AB  - Experience in successful treatment of 7 patients with isolated dissection of the
      abdominal aorta is presented. Over the last 10 years 165 patients with dissected
      aneurysms of different sites underwent surgery. In 7 (4.2%) of them isolated
      dissection of the abdominal aorta was diagnosed. Among 251 patients operated for
      abdominal aortic aneurysm dissection of its wall was seen in 2.8% cases.
      Morphologic study revealed atherosclerosis in 3 patients, degeneration of aortic
      wall - in 3, and combination of dysplasia with atherosclerosis - in 1. Linear
      prosthesis of abdominal aorta with replantation of visceral branches on single
      area into graft was the main (6) surgery. Bifurcation aorto-iliac prosthesis with
      bypass of the distal part of the deep femoral artery was performed in 1 patient.
      Five patients underwent elective surgery, 2 - emergency surgery.

PMID- 15159762
TI  - [Surgery of adrenal tumors].
AB  - From 1983 to 2003 examination and surgical treatment were performed in 463
      patients with different adrenal tumors. Hormone-active tumors were revealed in
      249 of them, non-active - in 214. Combination of CT or MRT with study of adrenal
      hormones is the basis of the diagnosis. In different cases multispiral computed
      tomography, angiography, selected taking of blood from inferior caval vein, US-
      or CT-guided biopsy were used. Open surgery through thoracofrenolumbotomy was
      performed in 392 patients, videolaparoscopic surgery - in 71. Expediency of
      laparoscopic surgery in line with open surgery is demonstrated.

PMID- 15159761
TI  - [Surgical treatment of ruptured abdominal aortic aneurysm].
AB  - Over the last 30 years more than 1000 patients with abdominal aortic aneurysms
      (AAA) were treated. Results of treatment of 367 patients with disruption of AAA
      from 1989 to 2002 were analyzed. Elderly and old patients account for 92% (338)
      of them. In 61% (224) patients after aneurysm's disruption blood outflew into the
      retroperitoneal space, in 23.4% (86) - into abdominal cavity, in 13,1% (48)
      patients retroperitoneal hematoma and hemoperitoneum formed, 2% (7) were the
      patients with functioning aorto-caval fistula, in 0.5% (2) aneurysm disrupted
      into the duodenum. There was no surgery due to different causes in 161 patients,
      all these patients died. One hundred and sixty-five patients underwent surgery,
      lethality was 60% (99 patients). Linear grafting of the aorta or aorto-iliac
      grafting was performed in the majority of patients - 77 (46.7%). Based on the
      obtained data three types of clinical picture of AAA disruption are devined:
      fulminant, acute and sub-acute. Complex treatment improved results of the
      treatment: lethality from 1989 to 1996 was 71.6%, from 1997 to 2002 - 52%.

PMID- 15159763
TI  - [Minimally invasive methods of surgical treatment for diseases of liver, biliary
      tract, and pancreas].
AB  - Results of examination of 324 biopsies from hepatopancreatoduodenal zone were
      analyzed. The biopsy was performed as roentgentelevision- or US-guided procedure
      with Pro-Mag 2.2 device. There were no complications. Percutaneous endoprosthesis
      of biliary ducts was performed in 127 patients (89% of them were older than 65
      years) with obstructive jaundice. Roentgen- or gastroscopy-guided
      hepaticogastroanastomosis was formed in 36 patients with different diseases. The
      follow-up was to 18 months in malignant tumors, and to 26 months in benign
      strictures. Video-assisted drainage of gall bladder in acute cholecystitis was
      performed in 436 patients with cholelithiasis and severe concomitant diseases.
      Results of many-stage treatment of 207 patients with choledocholithiasis were
      analyzed, residual disease was revealed in 11 (5.6%) patients.

PMID- 15159764
TI  - [Combined treatment of acute pancreatitis and its complications].
AB  - Results of combined treatment of 314 patients with acute pancreatitis, including
      58 (15.1%) with pancreonecrosis were analyzed. Etiologic factors of acute
      pancreatitis were alcohol (59% patients), diseases of the bile ducts (31.5%),
      surgery (2.5%). Up-to-date diagnostic criteria of severe pancreatitis are
      presented, character of complications is analyzed. Treatment policy in acute
      edematous pancreatitis was conservative. In calculous cholecystitis
      cholecystectomy was performed after regress of acute pancreatitis. Fermentative
      ascitis-peritonitis was the indication for laparoscopy in aseptic phase of
      pancreonecrosis. US- and CT-guided puncture and drainage were often used.
      Surgeries were performed only for complications of pancreonecrosis, more often
      through mini-approaches. General lethality in acute pancreatitis was 1.9%, in
      pancreonecrosis - 10.7%, postoperative lethality in pancreonecrosis was 16.6%.

PMID- 15159765
TI  - [Microsurgical autotransplantation of tissues in emergency surgery].
AB  - Results of microsurgical transplantation of 177 autotransplants in 167 patients
      with tissues defects of different origin and location are presented. Surgeries
      were urgent and elective with 96.6% survival of autotransplants. Short- and long
      term results of surgery were assessed. It is concluded that microsurgical
      techniques of treatment are more reliable and cost-effective than traditional
      ones. Expediency of microsurgical autotransplantation in urgent surgery is
      demonstrated.

PMID- 15159766
TI  - [Compression anastomoses and their creation by SCD devices in experiment and
      clinical practice].
AB  - New suture compression device (SCD) is developed and used in 119 patients for
      formation of esophageal-intestinal (10), esophageal-gastric (4), gastro
      intestinal (10), intestinal-intestinal (19), intestinal-colon (18) and colon
      colon (58) anastomosis. Insufficiency of sutures was seen in 2 (1.68%) patients
      after left-sided hemicolectomy (1) and resection of the sygmoid colon. One
      patient died, lethality was 0.84%.

PMID- 15159767
TI  - A new approach for the identification of modifier genes in heart failure.

PMID- 15159769
TI  - Takehiko Kitamori.

PMID- 15159770
TI  - 1-D nanochannels fabricated in polyimide.
AB  - A simple method using spin-deposition and sacrificial layer etching is used to
      fabricate all-polyimide nanochannels (100 and 500 nm channel height). Channels
      are characterized using spontaneous capillary filling with water, ethanol and
      isopropanol, and with electroosmotic flow. The channels can be produced with
      simple cleanroom equipment, namely spinning and metal deposition facilities.
      Polyimide is an excellent material for micro- and nanofluidic channels due to its
      favourable electrical and mechanical properties and its biocompatibility.

PMID- 15159768
TI  - Dietary intake, physical activity, and obesity in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine whether dietary intake and physical activity contribute
      to obesity in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control
      study. SUBJECTS: A total of 84 cases and 79 neighborhood controls of similar age.
      MEASUREMENTS: Fasting insulin, body mass index (BMI, kg/m2), waist/hip ratio,
      Block Food Frequency Questionnaire, Paffenbarger Physical Activity Questionnaire.
      RESULTS: Although women with PCOS had a higher BMI than control women, an overall
      comparison of women with and without PCOS showed no significant difference in
      dietary intake. However, stratification by BMI revealed that lean women with PCOS
      reported significantly lower energy intake than lean women without PCOS.
      CONCLUSION: Differences in dietary intake and physical activity alone are not
      sufficient to explain differences in weight between women with and without PCOS.
      Further research is necessary to determine the relative contributions of
      lifestyle factors and metabolism to obesity in PCOS.

PMID- 15159771
TI  - Generation of dynamic temporal and spatial concentration gradients using
      microfluidic devices.
AB  - This paper describes a microfluidic approach to generate dynamic temporal and
      spatial concentration gradients using a single microfluidic device. Compared to a
      previously described method that produced a single fixed gradient shape for each
      device, this approach combines a simple "mixer module" with gradient generating
      network to control and manipulate a number of different gradient shapes. The
      gradient profile is determined by the configuration of fluidic inputs as well as
      the design of microchannel network. By controlling the relative flow rates of the
      fluidic inputs using separate syringe pumps, the resulting composition of the
      inlets that feed the gradient generator can be dynamically controlled to generate
      temporal and spatial gradients. To demonstrate the concept and illustrate this
      approach, examples of devices that generate (1) temporal gradients of homogeneous
      concentrations, (2) linear gradients with dynamically controlled slope, baseline,
      and direction, and (3) nonlinear gradients with controlled nonlinearity are shown
      and their limitations are described.

PMID- 15159773
TI  - Stereoselective alkylation of an Evans auxiliary derivative within a pressure
      driven micro reactor.
AB  - A simple technique for the diastereoselective alkylation of a metal stabilised
      enolate is demonstrated within a pressure-driven micro reactor whereby enhanced
      diastereoselectivities were obtained compared to batch.

PMID- 15159772
TI  - Controlled rotation of biological micro- and nano-particles in microvortices.
AB  - Micrometer-sized re-circulating flows generated in a microfluidic system are used
      to drive the controlled rotation of biological particles of both micro- and nano
      meter scale dimensions. This technique is independent of the intrinsic nature of
      the particle, and possesses the potential to rotate particles at high rates. We
      demonstrate in such microvortices the orientation control of single DNA
      molecules, and the axial rotation of biological cells in which the cellular
      contents were visibly affected by rotation.

PMID- 15159774
TI  - Transport, retention and fluorescent measurement of single biological cells
      studied in microfluidic chips.
AB  - Cellular manipulation and fluorescent measurement were performed on two types of
      biological cells. First, transport and retention of yeast cells were demonstrated
      on a glass microfluidic chip, which consists of special U-shaped microstructures.
      These microstructures have the openings parallel to the liquid flow and weirs
      perpendicular to the flow. These allow the retention of yeast cells in the U
      shaped pocket and drainage of liquid over the weirs. Thereafter, the same chip
      was used to carry out real-time fluorescent measurement for the cellular changes
      in single Jurkat T cells. In this case, the Jurkat cells were localized inside
      the straight portion of a microchannel. Fluorescent imaging on the same, single
      suspension cell was carried out to study two cellular processes occurring in
      viable cells, (1) the intracellular conversion of fluorescein diacetate (FDA) to
      fluorescein; (2) the degradation of an inhibitory protein, IkappaB, as involved
      in the NF-kappaB signalling pathway. In the former, the increase in fluorescent
      intensity of single Jurkat T cells (due to fluorescein formation) was measured;
      whereas in the latter, the decrease in the fluorescent intensity of a single
      transfected Jurkat cell (due to the degradation of the IkappaB-EGFP fusion
      protein) was monitored. In addition, we employed a Jurkat cell expressed with
      IkappaB-EGFP to probe any possible action of an herbal compound,
      isoliquiritigenin (IQ), on the degradation of IkappaB-EGFP. These examples have
      demonstrated that Jurkat cells remain viable within microfluidic channels for
      cellular studies and that the microfluidic chip can facilitate monitoring of
      cellular changes of biological cells at the single cell level and in the same
      cell.

PMID- 15159775
TI  - Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle
      based DNA analysis.
AB  - An extremely simple, power-free pumping method for poly(dimethylsiloxane)(PDMS)
      microfluidic devices is presented. By exploiting the high gas solubility of PDMS,
      the energy for the pumping is pre-stored in the degassed bulk PDMS, therefore no
      additional structures other than channels and reservoirs are required. In a Y
      shaped microchannel with cross section of 100 microm width x 25 microm height,
      this method has provided flow rate of 0.5-2 nL s(-1), corresponding to linear
      velocity of 0.2-0.8 mm s(-1), with good reproducibility. As an application of the
      power-free pumping, gold nanoparticle-based DNA analysis, which does not rely on
      the cross-linking mechanism between nanoparticles, has been implemented in a
      microchannel with three inlets. Target 15mer DNA has been easily and
      unambiguously discriminated from its single-base substituted mutant. Instead of
      colorimetric detection in a conventional microtube, an alternative detection
      technique suitable for microdevices has been discovered-observation of deposition
      on the PDMS surfaces. The channel layout enabled two simultaneous DNA analyses at
      the two interfaces between the three laminar streams.

PMID- 15159776
TI  - Embryonic development in the mouse is enhanced via microchannel culture.
AB  - Microfluidic devices (microchannels) have been fabricated and tested for embryo
      culture. Three different microfabrication materials (silicon,
      polydimethylsiloxane (PDMS), and borosilicate) were used to fabricate the
      microchannels. The objective of this study was to determine if static
      microchannels permitted culture of mouse embryos to the blastocyst stage. Groups
      of 10 two-cell ICR x B6SJL/F1 mouse embryos were cultured for 96 hours in 4
      different physical culture systems: 1) silicon/borosilicate microchannels, 2)
      PDMS/borosilicate microchannels, and 3) standard microdrops. Embryos cultured in
      the silicon/borosilicate and PDMS/borosilicate microchannels exhibited a faster
      rate of cleavage (P < 0.05), and produced more blastocysts (P < 0.01) than
      control microdrops. Furthermore, microchannels had a lower percentage of
      degenerated embryos than control embryos (P < 0.01). The results suggest that the
      microchannel culture systems may provide a culture environment that more closely
      mimics the in vivo environment.

PMID- 15159777
TI  - One-step immobilization of aminated and thiolated DNA onto
      poly(methylmethacrylate) (PMMA) substrates.
AB  - Direct immobilisation of modified DNA oligonucleotides (aminated or thiolated)
      onto a plastic substrate, poly(methylmethacrylate), (PMMA) is described. Using
      the methyl esters present on non-modified PMMA, it was possible to establish a
      covalent bond between the electron donor of a DNA probe and the C terminal ester
      of the PMMA substrate. Since the procedure consists of a single brief wash in
      isopropanol or ethanol, the procedure is simple and environmentally friendly. The
      new immobilization strategy was characterized by analysing DNA microarray
      performance. The new procedure resulted in probe- and hybridization densities
      that were greater or equivalent to those obtained with commercially available
      surfaces and other procedures to immobilize DNA onto PMMA. The described
      chemistry selectively immobilized the DNA via terminal thiol or amine groups
      indicating that probe orientation could be controlled. Furthermore, the chemical
      bond between the immobilized DNA and the PMMA could endure repeated heat cycling
      with only 50% probe loss after 20 cycles, indicating that the chemistry could be
      used in integrated PCR/microarray devices.

PMID- 15159778
TI  - Optical tweezers applied to a microfluidic system.
AB  - We will demonstrate how optical tweezers can be combined with a microfluidic
      system to create a versatile microlaboratory. Cells are moved between reservoirs
      filled with different media by means of optical tweezers. We show that the cells,
      on a timescale of a few seconds, can be moved from one reservoir to another
      without the media being dragged along with them. The system is demonstrated with
      an experiment where we expose E. coli bacteria to different fluorescent markers.
      We will also discuss how the system can be used as an advanced cell sorter. It
      can favorably be used to sort out a small fraction of cells from a large
      population, in particular when advanced microscopic techniques are required to
      distinguish various cells. Patterns of channels and reservoirs were generated in
      a computer and transferred to a mask using either a sophisticated electron beam
      technique or a standard laser printer. Lithographic methods were applied to
      create microchannels in rubber silicon (PDMS). Media were transported in the
      channels using electroosmotic flow. The optical system consisted of a combined
      confocal and epi-fluorescence microscope, dual optical tweezers and a laser
      scalpel.

PMID- 15159780
TI  - Aggregation of bead-monolayers in flat microfluidic chambers - simulation by the
      model of porous media.
AB  - In this paper, we for the first time simulate the process of hydrodynamic bead
      aggregation in a flat micro-fluidic chamber by a porous-media model in an
      iterative routine. This allows us to optimize the chamber design of our recently
      developed experimental method to form periodical monolayers from the flow of bead
      suspension. Periodical monolayers are advantageous for parallel assay formats
      since they enhance the mechanical rigidity of the aggregated pattern. This is
      important to avoid a spatial rearrangement along various steps of a read-out
      procedure which would impair the correlation between measurements. Furthermore,
      the monolayer formation guarantees the individual optical accessibility of all
      probe beads. By modelling the monolayers with porous media, we can drastically
      reduce the degrees of freedom in a two-phase, multi-particle problem. This way,
      we are able to compute stationary hydrodynamic flow patterns in the chamber. In
      order to simulate the complete filling process from these stationary solutions,
      we developed an iterative master routine which takes the transient aggregation
      pattern as the initial condition, then evaluates the placement of the newly
      introduced beads, and finally converts the points of aggregation into porous
      media.

PMID- 15159779
TI  - Modeling microflow and stirring around a microrotor in creeping flow using a
      quasi-steady-state analysis.
AB  - The microflow and stirring around paramagnetic particle microchains, referred to
      as microrotors, are modeled as a circular cylinder rotating about its radial axis
      at very low Reynolds number. Time scales for momentum transfer under these
      conditions are determined to be much smaller than those for boundary movement,
      hence a quasi-steady approximation can be used. The flow is derived at every
      instant from the case of a steady motion of a horizontally translating cylinder,
      with the rotation approximated to a series of differential incremental
      translations. A numerical simulation is used to determine the pathlines and
      material lines of virtual point fluid elements, which were analyzed to understand
      the behavior of the flow around the microrotor. The results indicate the flow to
      be unsteady, with chaotic advection observed in the system. The fluid motion is
      primarily two-dimensional, parallel to the rotational plane, with mixing limited
      to the immediate area around the rotating cylinder. Fluid layers, up to many
      cylinder diameters, in the axial direction experience the disturbance. Elliptic
      and star shaped pathlines, including periodic orbits, are observed depending on
      the fluid element's initial location. The trajectories and phase angles compare
      well with the experimental results, as well as with data from particle dynamics
      simulations. Material lines and streaklines display stretching and folding, which
      are indicative of the chaotic behavior and stirring characteristics of the
      system. The material lines have similar lengths for the same amount of rotation
      at different speeds, and the effect of rotational speeds appears to be primarily
      to change the time of mixing. The results are expected to help in the design of a
      particle microrotor based sensing technique.

PMID- 15159781
TI  - A fast passive and planar liquid sample micromixer.
AB  - A novel microdevice for passively mixing liquid samples based on surface tension
      and a geometrical mixing chamber is presented. Due to the laminar flow regime on
      the microscale, mixing becomes difficult if not impossible. We present a
      micromixer where a constantly changing time dependent flow pattern inside a two
      sample liquid plug is created as the plug simply passes through the planar mixer
      chamber. The device requires no actuation during mixing and is fabricated using a
      single etch process. The effective mixing of two coloured liquid samples is
      demonstrated.

PMID- 15159782
TI  - A new on-chip ESI nozzle for coupling of MS with microfluidic devices.
AB  - This paper presents a new on-chip electrospray ionisation (ESI) nozzle, which can
      be used as an interface for coupling microfluidic devices with mass spectrometric
      (MS) detection. The nozzle was micromilled in a polymer foil
      (polymethylmethacrylate (PMMA) 750 microm thick), normally used as a cover for
      microfluidic chips. The performance of this device was examined in the ESI-MS
      analysis of the tetrapeptide MRFA (methionine-argenine-phenylalanine-alanine).
      The spray quality is basically dependent on the inner diameter of the nozzle,
      beside the part of the organic modifier in the solution to be sprayed. Three
      different inner nozzle diameters (30, 50, 100 microm) and two different apex
      angles were investigated. Stable electrospray conditions can be generated with a
      relative standard deviation less than 10% of the total ion current, and down to a
      concentration of 0.01 micromol L(-1). The production of this ESI interface is
      relatively simple for the purpose of a low-cost batch fabrication of miniaturized
      analytical instruments.

PMID- 15159783
TI  - Electrophoretic manipulation of single DNA molecules in nanofabricated
      capillaries.
AB  - We demonstrate the use of nanofabricated capillaries, integrated as part of a
      microfluidic structure, to study the electrophoretic behaviour of single,
      fluorescently-labelled, molecules of DNA as a function of capillary size. The
      nanocapillaries, fabricated using a focused ion beam, have cross-sections down to
      150 x 180 nm. Control of single-molecule direction and velocity was achieved
      using voltage manipulation. DNA mobility was found to increase with decreasing
      cross-section, which we interpret in terms of reduced electro-osmotic counter
      flow. Such nanofabricated capillaries as part of larger fluidic structures have
      great potential for biotechnology, particularly single molecule manipulation and
      analysis.

PMID- 15159784
TI  - Electroosmotic flow with Joule heating effects.
AB  - Electroosmotic flow with Joule heating effects was examined numerically and
      experimentally in this work. We used a fluorescence-based thermometry technique
      to measure the liquid temperature variation caused by Joule heating along a micro
      capillary. We used a caged-fluorescent dye-based microfluidic visualization
      technique to measure the electroosmotic velocity profile along the capillary.
      Sharp temperature drops close to the two ends and a high-temperature plateau in
      the middle of the capillary were observed. Correspondingly, concave-convex
      concave velocity profiles were observed in the inlet-middle-outlet regions of a
      homogeneous capillary. These velocity perturbations were due to the induced
      pressure gradients resulting from axial variations of temperature. The measured
      liquid temperature distribution and the electroosmotic velocity profile along the
      capillary agree well with the predictions of a theoretical model developed in
      this paper.

PMID- 15159785
TI  - Application of a microfluidic reaction system for CdSe nanocrystal preparation:
      their growth kinetics and photoluminescence analysis.
AB  - We used a microreactor for CdSe nanocrystal preparation and explored the effects
      of experimental conditions on the properties of the products. The particle growth
      kinetics and photoluminescence properties of the nanocrystals showed identical
      trends to previous reports, indicating the efficiency of the current method for
      analysis of rapid nanocrystal synthesis as well as industrial production of CdSe
      nanocrystals.

PMID- 15159786
TI  - Dielectric spectroscopy in a micromachined flow cytometer: theoretical and
      practical considerations.
AB  - We propose a model to determine the influence of different cell properties, such
      as size, membrane capacitance and cytoplasm conductivity, on the impedance
      spectrum as measured in a microfabricated cytometer. A dielectric sphere of
      equivalent complex permittivity is used as a simplified model to describe a
      biological cell. The measurement takes place between a pair of facing
      microelectrodes in a microchannel filled with a saline solution. The model
      incorporates various cell parameters, such as dielectric properties, size and
      position in the channel. A 3D finite element model is used to evaluate the
      magnitude of the electric field in the channel and the resultant changes in
      charge densities at the measurement electrode boundaries as a cell flows past.
      The charge density is integrated on the electrode surface to determine the
      displacement current and the channel impedance for the computed frequency range.
      The complete impedance model combines the finite element model, the electrode
      electrolyte interface impedance and stray impedance, which are measured from a
      real device. The modeled dielectric complex spectra for various cell parameters
      are discussed and a measurement strategy for cell discrimination with such a
      system is proposed. We finally discuss the amount of noise and measurement
      fluctuations of the sensor.

PMID- 15159787
TI  - Sampling small volumes of ambient ammonia using a miniaturized gas sampler.
AB  - The development of a gas sampler for a miniaturized ambient ammonia detector is
      described. A micromachined channel system is realized in glass and silicon using
      powder blasting and anodic bonding. The analyte gas is directly mixed with
      purified water, dissolving the ammonia that will dissociate into ammonium ions.
      Carrier gas bubbles are subsequently removed from the liquid stream through a
      venting hole sealed with a microporous water repellent PTFE membrane. A flow
      restrictor is placed at the outlet of the sampler to create a small overpressure
      underneath the membrane, enabling the gas to leave through the membrane.
      Experiments with a gas flow of 1 ml min(-1), containing ammonia concentrations
      ranging from 9.4 ppm to 0.6 ppm in a nitrogen carrier flow have been carried out,
      at a water flow of 20 microl min(-1). The ammonium concentration in the sample
      solution is measured with an electrolyte conductivity detector. The measured
      values correspond with the concentration calculated from the initial ammonia
      concentration in the analyte gas, the fifty times concentration enhancement due
      to the gas-liquid volume difference and the theoretical dissociation equilibrium
      as a function of the resulting pH.

PMID- 15159788
TI  - [Neurotransmitters, calcium signalling and neuronal communication].
AB  - In this article we show some recent findings that constitute a great progress in
      the molecular knowledge of synaptic dynamics. To communicate, neurons use a code
      that includes electrical (action potentials) and chemical signals
      (neurotransmitters, neuromodulators). At the moment a great variety of molecules
      are known, whose neurotransmitter function in brain and the peripheral nervous
      system are out of question. Monoamines like acetylcholine, dopamine,
      noradrenaline, adrenaline, histamine, serotonin, glutamate, aspartate, glycine,
      ATP and GABA are good examples. Opioid neuropeptides, vasoactive intestinal
      peptide (VIP), neurokinines (substance P), somatostatin, neurotensin,
      neuropeptide Y, cholecystokinine, vasopressin or oxitocin have been related to
      the control of the stress response, sexual behaviour, food intake, pain, learning
      and memory, qualities that are also related to nitric oxide (NO). A great part of
      the molecular structure of the secretory machinery is known to be responsible for
      fast neurotransmitter release at the synapse, in response to action potentials.
      Proteins like sinaptobrevin (located in the membrane of the synaptic vesicle),
      sintaxin and SNAP-25 (both located at the presynaptic plasma membrane) constitute
      a trimeric complex which is responsible of the vesicular docking at the active
      sites for exocytosis. From this strategic location, vesicles release their
      neurotransmitter within few milliseconds, when the action potential invades the
      nerve terminal and activates the opening of the different subtypes of voltage
      dependent Ca2+ channels. The asymmetric geographical distribution of each type of
      channel, in different neurons, rose the hypothesis that Ca2+ that enters through
      each subtype of channel is compartmentalised, thus favouring the generation of
      Ca2+ microdomains, in the cytosol and the nucleus, involved in different cellular
      functions. This great biochemical synaptic heterogeneity is facilitating the
      selection of many biological targets to develop drugs with potential therapeutic
      applications in neuropsychiatric diseases i.e. Alzheimer's, Parkinson,
      epilepsies, stroke, vascular dementia, depression, schizophrenia, anxiety and so
      on.

PMID- 15159789
TI  - [Tentorial meningiomas. Report of our series].
AB  - PURPOSE: The main objectives of this report are to describe the clinical and
      radiological features, surgical management, complications, and final outcome of
      patients with a tentorial meningioma. METHODS: This is a retrospective study of
      25 patients operated on for tentorial meningiomas at our department since
      december 1975 to may 2002. All the patients, except the first, were diagnosed by
      computed tomography; in 13 of them a magnetic resonance imaging was performed
      too; in 14 patients, diagnosis was completed with cerebral arteriography. The
      preoperative clinical condition, the interval between the first symptoms and the
      date of the operation, the postoperative morbidity and the recurrence are
      analysed. RESULTS: There were 20 women and 5 men of ages ranging from 35 to 79
      years (average of 54.6). Surgical removal was considered radical (Simpson I-II)
      in 22 patients. Of them one had a recurrence 25 years after the operation,
      another had three recurrences, in two years, that were reoperated, and a third
      one had recurrence at five years who did not require surgery. The postoperative
      mortality was 8%. The mean follow-up period was of 5.3 years. The final outcome
      was good recovery in 19 patients, moderate disability in 1 and death in 4.
      CONCLUSIONS: Despite the advances in Neuroradiology and Microsurgery, these
      tumors represent a challenge for the neurosurgeon, due in some cases to a large
      tumor size and extension to critical areas. A removal as complete as possible
      allows minimizing the recurrence risk.

PMID- 15159790
TI  - [Treatment of central neurocytoma. Experience at a single institution].
AB  - Central neurocytomas are classically considered as a rare, intraventricular
      benign tumours with neuronal differentiation derived from precursor cells of
      subventricular matrix. However some patients with neoplasms with histologic
      atypia and elevated proliferation potential may have a poor outcome. Treatment of
      choice is complete surgical excision. Adjuvant therapy is reserved for patients
      with residual or recurrent lesions including reoperation, radiotherapy or
      chemotherapy. We review our experience with the treatment of this neoplasm. Five
      patients with an intraventricular mass studied with magnetic resonance imaging
      underwent craniotomy for tumour resection. All cases were reviewed
      retrospectively. Histopathological analysis confirmed central neurocytoma in all
      cases. Proliferation index was assessed by Ki-67 immunohistochemistry. Complete
      radiological tumor resection through transcortical approach was achieved in all
      except one patient. In this case adjuvant therapy with radiosurgery was given
      with important reduction in tumor size. All the tumours had a proliferation index
      below 2% except one with 5%. Follow-up in four patients ranged from 12 to 36
      months. There were no tumour recurrences in this period. Complete surgical
      excision of central neurocytoma provides better local control and survival
      compared with other treatments. Radiosurgery as adjuvant therapy in incomplete
      resections may eliminate the need of reoperation and avoid long-term side effects
      from conventional radiotherapy.

PMID- 15159791
TI  - [Lasegue's test as prognostic factor for patients undergoing lumbar disc
      surgery].
AB  - INTRODUCTION: In patients operated for herniated lumbar disc it could be very
      useful to develop physical examination criteria that would allow early prediction
      of medium or long term clinical outcomes. The result of the Lasegue test after
      surgery depends on the occurrence of recurrent herniated disc and/or scar
      formation around the nerve root. Previous studies have shown the association
      between the result of Lasegue test, assessed 4 months after surgery, and the
      short term functional outcome. OBJECTIVE: To determine the prognostic value of
      postoperative Lasegue test in relation with medium term functional and clinical
      outcomes which were estimated by analyzing the functional grade, employment
      status, quality of life, reoperation for recurrent disc herniation, and the
      number of clinical revisions and imaging studies needed during the follow-up.
      PATIENTS AND METHODS: 243 patients who underwent hemilaminectomy for lumbar
      herniated disc between 1996 and 2002 were studied. The Lasegue sign was tested 3
      months after surgery. A modification of Spangfort's criteria (to measure the
      functional grade) and the 12-item Short-form health survey (SF-12) method (to
      measure the quality of life) were used to quantify outcomes at 12, 24 and 36
      months after initial surgery. RESULTS: This investigation has proved the
      prognostic value of Lasegue test assessed 3 months after initial surgery. A
      statistically significant correlation was found between a positive straight leg
      raising test and a poor functional status at 24 and 36 months, and the risk do
      not return to work because of persistent pain at 12, 24 and 36 months. A
      statistically significant correlation was also found between the result of the
      test and the frequency of reoperation for recurrent disc herniation and the
      number of clinical revisions and imaging control studies needed through the
      follow-up. Likewise, the prognostic value of Lasegue test on different aspects of
      quality of life (health perception, functional performances, poor social
      interaction and severe pain) analyzed at 24 and 36 months after surgery were also
      confirmed. CONCLUSION: This study provides additional information about the
      predictive value of the straight leg raising tested 3 months after surgery on the
      clinical (diagnostic resources consumption, successive outpatient revisions, etc)
      and functional (quality of life, functional grade and return to work) outcomes
      assessed 24 and 36 months after initial surgery.

PMID- 15159792
TI  - [Survival analysis following the addition of temozolomide to surgery and
      radiotherapy in patients with glioblastoma multiforme].
AB  - OBJECTIVES: To analyze the effect of different therapies -surgery, radiotherapy,
      and chemotherapy (temozolomide)- on the survival of various groups of patients
      with glioblastoma multiforme (GBM). METHOD: The overall survival of a total of 85
      patients with histopathological diagnosis of GBM was analyzed (descriptive
      statistics, Kaplan-Meier). Patients were divided into 4 treatment groups: group 1
      (n=12), untreated patients (" no treatment" option was chosen by the family);
      group 2 (n=22), patients undergoing surgery only (retrospective series from the
      1980s); group 3 (n=24), patients undergoing surgery + standard radiotherapy
      (control group, partially effective treatment); group 4 (n=27), patients
      undergoing surgery + radiotherapy + chemotherapy (temozolomide [TMZ]) (current
      study group). RESULTS: Mean age (one-way ANOVA) showed no significant difference
      between the groups. Mean/median survival (weeks) was as follows: group 1, 18/16;
      group 2, 23/14; group 3, 48/42; group 4, 70/64. The Kaplan-Meier analysis yielded
      the following 50% survival cutoffs (weeks): group 1, 16.00; group 2, 14.29; group
      3, 42.00; group 4, 64.43. This demonstrated a significant difference when
      radiotherapy (group 3) was added to surgery (group 2) or no treatment (group 1),
      and a significant difference (p < 0.001) in survival when TMZ (group 4) was added
      to the so far considered as being the standard treatment (group 3: surgery +
      radiotherapy). CONCLUSIONS: Surgery alone does not result in a higher survival
      rate for GBM patients. However, surgery allows to establish a histopathological
      diagnosis, to improve signs and symptoms which are attributable to intracranial
      hypertension or tumour topography, and to reduce the number of target cells for
      adjunctive therapies. Radiotherapy improves survival and TMZ chemotherapy that is
      given after radiotherapy adds further survival benefit for patients.

PMID- 15159793
TI  - [Activity of copper-zinc superoxide dismutase in a global ischemic brain lesion
      model without arterial hypotension].
AB  - OBJECTIVE: To determine the behavior of the copper-zinc superoxide dismutase
      enzyme (SOD/Cu/Zn) in tissue homogenates of rat brains with ischemic lesions
      produced following the model of global cerebral ischemia without arterial
      hypotension. MATERIAL AND METHODS: Thirty rats were randomly assigned to five
      groups of six animals each. Bilateral carotid occlusion was temporarily produced
      in 24 rats (4 groups) during periods of 5, 15, 30 and 60 minutes, respectively.
      All the animals were then submitted to reperfusion for 30 minutes and after that,
      they were sacrificed. A control group of 6 rats was not exposed to arterial
      occlusion. Cerebral homogenates of the rats' brain were obtained and submitted to
      spectrophotometer analysis. RESULT: The control group showed the lowest mean
      values in SOD/Cu/Zn activity (40.60+/-11.42 U/mg of protein), while the highest
      mean values (60.34+/- 13.52 U/mg of protein) corresponded to the rats submitted
      to ischemia for 60 minutes, what indicates a statistically significant difference
      (p = 0.016) between the two groups. CONCLUSIONS: SOD/Cu/Zn activity in rats
      increases during the production of ischemic cerebral lesions. The analysis of
      SOD/Cu/Zn activity showed an important tendency to rise from the 30 minutes
      period of ischemic lesion and reached statistically significant values at 60
      minutes from the beginning of the ischemic injury. The experimental model of
      global brain ischemia without arterial hypotension used in this study constitutes
      a reliable method for researching cerebral ischemia.

PMID- 15159795
TI  - [Acute spontaneous subdural haematoma of arterial origin].
AB  - INTRODUCTION: An acute subdural hematoma is often regarded as a complication of
      head trauma. Occasionally subdural bleeding from the rupture of a cerebral
      aneurysm or an arteriovenous malformations is described. Spontaneous subdural
      hematoma is, however, very rare and it commonly has an arterial origin and their
      aetiology is still a matter of controversy. OBJECTIVE: The purpose of this paper
      is to present eight cases of spontaneous subdural hematoma seen at our department
      during the last 19 years. The etiological possibilities of spontaneous subdural
      hematoma are discussed. PATIENTS AND METHODS: We analyzed 8 cases of acute
      spontaneous subdural hematoma among a total number of 321 patients with subdural
      hematoma is presented. RESULTS: There were six males and 2 females with a mean
      age of 52 years (range 20-66). All patients developed progressive neurological
      deficits, until become comatose. All eight patients were operated on and surgical
      mortality was 25%. CONCLUSIONS: Spontaneous subdural hematoma is a rare condition
      and the prognosis is mainly dependent on the pre-operative neurological state
      regardless of its origin or cause.

PMID- 15159794
TI  - [Silent corticotroph adenomas: presentation of two cases that presented with
      pituitary apoplexy].
AB  - Among the group of pituitary adenomas surgically treated, about 25-30% are not
      associated with clinical or analytical findings of hormonal hypersecretion. The
      development of immunohistochemical techniques has allowed the demonstration of a
      subgroup of adenomas that show immunoreactivity against several hormones among
      the group of, apparently, non-functioning adenomas. This subgroup has been called
      silent adenomas. Silent adenomas positive for ACTH show a singular clinical
      picture and different from those adenomas producing Cushing's disease, as they
      present more frequently as macroadenomas, with more frequent pituitary apoplexy,
      invasion of cavernous or sphenoidal sinus and recurrences. We present two new
      cases of silent corticotroph adenomas in two female patients that presented with
      pituitary apoplexy, one of them after giving birth after a normal full-term
      pregnancy. Both of them presented with macroadenomas that invaded the sphenoidal
      and cavernous sinus. Although both tumors were immunoreactive for ACTH, none of
      the patients presented clinical or analytical findings compatible with Cushing's
      disease.

PMID- 15159796
TI  - [Lingualoplasty with modified forearm flap: A preliminary report with 6 cases]
AB  - A modified technic with forearm flap for lingualoplasty after ablative surgery
      for tongue cancer is reported.The tongure flap is pedicaled with the root of
      tongue by the residual excixion margin,and an oblique incision is made on the
      side of the placed forearm flap.Finally,the tongue flap is inlaid into the
      forearm flap in order to increasing the moving activity and function of the
      flap.This method has been applied to treat 6 patients of the tongue cancer.For
      them,the objective comments for function of the tongue after operation was given.

PMID- 15159797
TI  - [Severe dentomaxillary deformity: Report of one case]

PMID- 15159798
TI  - [Radiologic similarity and dissimilarity of Histiocytosis X in the mandible
      between non adult and adult]
AB  - 28 cases of Histiocytosis X in the mandible were divided into two groups:the non
      adult group (19 cases,21 foci).and the adult group(9 cases,12 foci).their
      similarity and dissimilarity in radiological appearances were contrasted
      individually.The authors consider there were different roentgenographic
      manifestations between the two groups according to the diversity of
      physilological and morphological configuration in the mandible.The former group
      which had its characteristic roentgenologic feature displayed a radiolucent
      region with an irregular margin mostly accompanied with a periosteal reaction at
      the inferior and lateral surfaces of the mandible.Owing to lacking above
      mentioned demonstration,it was difficult to distinguish the lesions of later
      group from other disease in the mandible.

PMID- 15159799
TI  - [Treatment of recurrent aphtha ulcer with placenta fluid: Clinical evaluation]

PMID- 15159800
TI  - [Clinical analysis of 20 cases of lip carbuncle with lung infection]
AB  - 20 cases of lip carbuncle with lung infection were reviewed,the clinical
      characteristics,laboratory result and treatment of them were analysed.It is
      important that the unadvisable handles on lip carbuncle should be avoided,the
      complications should be found early,and the patients should be treated timely and
      effectively.

PMID- 15159802
TI  - [Treatment of trigeminal neuralgia with cryotherapy: A preliminary evaluation in
      27 cases]

PMID- 15159801
TI  - [Fibrous dysplasia of jaw and facial bones:A combined analysis of
      clinic,radiologic and histopathologic diagnosis of 117 cases]
AB  - A clinical-radiologic-histopathologic review of 106 cases of fibrous dysplasia
      involving the jaws is presented. Ninety eight patients onset in the first and
      second decades.Fifteen cases were polyostotic and the remaining cases were were
      monstotic.Radiologicaly,the lesions showed and extending growth pattern,poor
      definite border and slight pattern,poor definite border and slight involvement of
      teeth.The radiographic features were classified into four types:ground grass
      (52.0%),sclerotic(8.0%),cystic-like(8.0%) and mixed type (32.0%).Histologically
      the lesions were characterized by a cellular fibrous stroma that contain varying
      amounts of mineralized substance,represented by woven bone(63.0%),lamellar
      bone(30.0%) and cementum-like structure(7.0%).The final definitive diagnosis
      requires the combined evaluation of clinic,radiologic and histopathologic
      findings.

PMID- 15159803
TI  - [Clinical analysis of 40 cases of malignant tumor of the floor of the mouth]
AB  - This is a retrospective review for 40 patients with malignant tumour of the floor
      of mouth.In the group,squamous carinoma is 62.5%.adenoid cystic carcinoma is
      22.5%.Both of them are the major type,stage III.IV were 72.5%,Generally
      ipsilateral;radical mandibular and neck dissection was performed sellectively.65%
      of patient were given preoprative chemotherapy.Total 5 years survival rate was
      50%,for stage I-III were 78.6%.Although preoperative chemotherapy was given that
      the group of lower pathological differetiation was still in lower survival
      rate,higher recurrence and mortality than those given surgery alone. Survival
      rate for squamous carcinoma was higher than that for adenoid cystic carcinoma.

PMID- 15159804
TI  - [Analysis of 191 children first received in the department of dentistry]

PMID- 15159805
TI  - [The effect of iontophoresis on accelerating orthodontic tooth movement]
AB  - This paper reported that acceleration of tooth movement can be gained by
      submucosal injection of some kind of medicine.To avoid the pain caused by the
      injection,conventional drug administration was ameliorated in this study by
      adopting the method of ionophoresis rabibits were divided into 2 groups and the
      standard otthodontic appliances were placed in the lower incisors of all
      animals.The 2 groups were separately recieved submucosal iontophoresis and
      injection of 0.9% NaCl which served as control.The result showed that animals
      with iontophoresis,in whose periodontal pression side more osteoclasts were
      observed histologically,had gained rapider tooth movement than those with
      injections.

PMID- 15159806
TI  - [Development and application of CYW-KH type intellective occlusal force
      measurement appliance]

PMID- 15159807
TI  - [Study of the location of mandibular mental foremen in modern and neolithic
      adult]
AB  - 37 cases of mandible of Neolithic adult that both sexes without missing
      teeth,alveolar bone were studied.The result showed that the location of the
      mental foramen below the apex of the lower second premolar was the most
      common(67.97%) in the modern adult,and the location of the mental foramen below
      between the apex of the lower second premolar and the first molar was the most
      common (64.86%) in the neolithic adult.

PMID- 15159808
TI  - [Purification and characterization of lipoteichoic acid from Streptococcus
      Sobronus]
AB  - Lipoteichoic acid (LTA) is amphipathic molecule found in cell surface of gram
      positive bacteria.Although there were some hypothese about adhesion of LTA,the
      role of LTA in bacterial pathogenicety is still unclear.For this reason,a seria
      studies of LTA were carried out.In this study LTA was extracted by hot aqueous
      phenol from Strptococcus Sobronus 6715 grown in tryptic soy both supplemented
      with 5% sucrose for 17 hours,and was purfied on gel filtration by Sepharose
      6B,chloroform-methanol precipitation and chromtography on DEAE-Sephacel.The
      purified LTA was characterized by FT-IR and 1H-NMR with standard sample of LTA
      (Sigma Co) as control.The results showed that LTA contains alanine ester and
      glycosyl residues which take important role in the amphipathic molecule.

PMID- 15159809
TI  - [The characters on histopathological changes in dental fluorosis]
AB  - The microradiography SEM and TEM were used ton observe histopathological changes
      in dental fluorasis with various degrees in this study.The characters of
      histopathological changes of dental fluorasis are:(1) the lesios appear in
      exterior layer of enamel,not excess one third enamel.(2)the future of the lesion
      is enamel-hypoplasia,enamel rods were hypomineralized.the space among enamel rods
      widen and form some cavities.There are a lot of spaces in intercrystlines.Many
      micropores and injures exhibit on enamel surface.(3)the clinic severe degree of
      lesion is similar to the histopathological changes.It could be indicated using
      the Dean's and the TF index.

PMID- 15159810
TI  - [The study and protection of mercury contamination in silver amalgam on patient's
      safety]
AB  - The mercury concentration of oeal gas was determinded.Comparison were made on 2
      groups consisting of silver amalgam covered cases(n=15) and uncovered cases
      (n=29) immediately by vaseline after filling silver amalgam,and the concentration
      of Hg before polishing old silver amalgam and after polishing (n=10),The result
      showed there are very significant difference (P<0.01).The surface area of filling
      mercury amalgam did not relate to Hg concentration.The larger volume of polishing
      old mercury amalgam was,the higher concentration of Hg was.In addition,mercury
      concentrations of air in four consulting rooms before ventilation were higher
      than 3.1-6.6 times national hyienic standard,however,it was reduced to 1.2-2.1
      times after ventilation.

PMID- 15159811
TI  - [The methodological study of oral epidemiology]

PMID- 15159812
TI  - [Orthodontic treatment and root absorption: An overview]

PMID- 15159813
TI  - [Repair of periodontal bone defects with hydroxyapatite]

PMID- 15159814
TI  - [The up to date advances on treatment of trigeminal neuralgia]

PMID- 15159815
TI  - [Supernumerary teeth in 251 children: Clinical analysis]

PMID- 15159816
TI  - [TNM staging and classification for malignant tumors: III. Head and neck cancer
      (continued)]

PMID- 15159817
TI  - [Reconstruction of large performated maxillofacial defect with immediated
      revascularized flap]
AB  - Patients with large perforated maxillofacial defects resulting from combined
      craniomaxillofacial resection or extended extra cranio-maxillofacial resection
      due to malignances in this region had been reconstructed with large
      revascularized myocutaneous flap or combined pedicled myocutaneous flap with
      revascularized flap.Since January,1981,a total of 29 flaps was used,of which 28
      flaps survived successfuly,whereas one free forearm flap being failed to survive
      due to venous embolization was replaced with pedicled forehead flap.The results
      in postoperative appearance and rehabilitation of physiological function were
      relatively satisfactory.Finally,selection of flap and method of reconstruction
      were introduced and experiences on immediate reconstruction after malignance
      resection reported.

PMID- 15159818
TI  - [Putrid and necrotic cellulitis of the floor of mouth concomitant with hemorrhage
      from the digestive tract: Report of one dead case]

PMID- 15159819
TI  - [Quantitatively study of voice onset time-Glottal stop]
AB  - To quantitatively evaluate the acoustic characteristics of glottal stop,
      pronunciation of/ka/in 10 normal subjects and 14 patients with cleft palates were
      analyzed by sound spectrography and 20 msec in all normal articulation of /ka/
      with an average time of 44.6 msec.In the test group of /ka/ demonstrated an
      average time of 20.8 msec.The inverse correlation ship between VOT and the psyco
      acoustical judgment for the degree of distortion was demonstrated to be
      significant.

PMID- 15159820
TI  - [The relation between recurrent oral ulcer and cholelithic jaundice]

PMID- 15159821
TI  - [Restoration with light curing composite resin: Technical pitfalls]

PMID- 15159822
TI  - [The clinical observation of 247 tuberculosis cases in Oral Maxillofacial region]
AB  - This paper presents a report of clinical observation on tuberculosis of oral and
      maxillofacial region in 247 patients.Of these which diagnosed by
      histopathology.94 cases are from mucous membrane of oral cavity,108 subjects from
      lymph nodes,27 ones from parotid gland,15 persons from facial dermis and 3 from
      jaw.Among 247 patients.154 cases were male and 93 female.The youngest was 2 years
      old and the eldest one was 71 of age and the mean age was 32 years old.The
      shortest course of disease was 15 days and the longest was 30 years,the mean
      course of time was two and half years.The rate of clinical diagnosis accord with
      pathology was 41.3%,most error diagnosis were to suspect inflammation,tumors and
      ulcer.In addition,the etiology,the clinical manifestion,diagnosis and therapies
      of oral and maxillofacial tuberculosis were analyzed.

PMID- 15159823
TI  - [The relationship between periodontal diseases and prostacyclin in saliva of
      periodontal patients by RIA]
AB  - The purpose of this investigation was to measure the changes of
      Prostacyclin(PG12) occuring in gingivitis and periodontitis.Fifteen cases of
      periodontitis,ten cases of gingivitis and ten cases of healthy participated in
      this study,Saliva was taken before treatment,Prostacyclin in saliva was measure
      by radioimmunoassay(RIA).The results showed that prostacyclin of human saliva is
      increased from healthy gingivitis to periodontitis.There is a statistical
      difference between groups,6-k-PGF1alpha in saliva of periodontitis is 3.6 folds
      of healthy.Gingivitis is 2.6 folds of healthy.There is also a significant
      difference between adult periodontitis our findings suggested that prostacyclin
      may play an important role in etiology of periodontal disease.Measured 6-k
      PGF1alpha in saliva may indicate the severity of periodontal disease.

PMID- 15159824
TI  - [The application of frozen homogenic brephobone in surgical treatment of chronic
      periapical periodontitis]
AB  - Clinical effectiveness of frozen homogenic brephobone as a filling material in
      the treatment in the treatment of chronic periapical periodontitis was
      evaluated.42 patents with chronic periapical periodontitis,periapical,cyst and
      periapical granuloma were observed.After apical curettage was performed,22 cases
      were filled with frozen homogenic brephobone and other cases were close bone
      cavity with traditional treatment.All these cases were then covered with
      periodontal packing agent.Radiograph and clinical observation were made
      respectively at 2 week,1 month,3 month,6 month and 12 month recall visit
      following the surgery.It was found that the way of filling with frozen homogenic
      brephobone is more advantageous than the traditional way.

PMID- 15159825
TI  - [Pilomatricomas of the tip of tongue: Report of one case]

PMID- 15159826
TI  - [The research on instant treatment of apical periodontitis with porous
      hydroxyapatite ceramic]
AB  - This paper described how to use hemorheology to observe the oral and
      maxillofacial inflammation.60 cases were reported,and 60 normal cases as control
      group.It revealed that etap of the oral maxillofacial inflammation were much
      higher than that of normal person(P<0.01),etab,etab-1/H,ESR,FA of the oral
      maxillofacial inflammation were higher than that of normal person(P<0.05).Because
      the disease belongs to the spectrum of blood stasis.The treatment method of the
      promoting blood circulation and removing blood stasis can be used in additional
      to the normal remedy.

PMID- 15159827
TI  - [Initial investigation of the value of CT in pulmonary metastases originating
      from head and neck malignant tumors]
AB  - CT image and its diagnostic value were analyzed and compared with plain chest
      film on 12 cases of pulmonary metastases originating from malignant tumors of
      head and neck,all cases were pathologically verified.CT scan performed on each
      cases who had definite or suspicious lesion on plain chest film.The result
      presents that CT can:(1)confirm the suspiciousness of metastatic
      lesion.(2)confirm the number of metastatic lesion.(3)early detection on pulmonary
      metastasis. 4.identification on occult pulmonary metastasis. 5.Find out costal
      bone and pleural metastasing accuracy of pulmonary metastasis,but also provide
      information for clinical selecting treatment.

PMID- 15159828
TI  - [Stress analysis with a laser microscope analyzer for acrylic base resin]
AB  - Acrylic resin are applied widely as a denture resin,its residual stress is
      closely related with aging and mechanical properties of denture resin.The authors
      tested the stress level of the base resin with a laser microscope stress analyzer
      in the study.The results indicated that there was not statistical differences
      between two curing methods is in water bath or under pressure.The residual stress
      in base resin can be concentrated at the area near to clasp wire which was
      embedded in base resin for reinforcing strength of denture base.The vibration
      caused by grind with stone wheel or impact in disc lasting with a hammer may
      increase the stress level in base.The authors pointed out some methods for
      reducing residual stress resin.

PMID- 15159829
TI  - [Immunohistochemical localization of CEA,EMA and keratin in salivary
      mucoepidermal carcinoma]
AB  - Localizations of CEA,EMA and keration in 19 cases of mucoepidermal carcinomas
      were investigated using the indirect immunoperoxidase technique.The results
      showed CEA was negative in normal salivary glands and showed faint reaction in
      glands near carcinoma tissue.Keratin and EMA were localized in some myoepithelial
      cells.The positive rates in carcinoma tissue were 78.9%,89.5% and
      84.2%,respectively.The positive rates and staining intensity of CEA and EMA in
      carcinoma tissue gradually decreased with the decline of tumor
      differentitation,but that of keratin showed no variation.the author consider that
      CEA and EMA could become good indices in clinically diagnosing mucoepithelial
      carcinoma and determining tumor differentiation type cell in mucoepidermal
      carcinoma and have a potential to multiply express the tumor elements of
      epithelium and/or mesenchyma.

PMID- 15159830
TI  - [The facial skeletal characteristics for adults in Shanghai with normal
      occlusion;the quadrilateral analysis]
AB  - 60 adults of Han nationalities in Shanghai with normal occlusion were selected
      for the quadrilateral analysis of cephalograms.The study showed that there
      existed a definite ratio between the jaw bone and the tooth.The purpose of his
      investigation was to obtain the ratio and the nature of the malocclusion and make
      up a reasonable orthodontic treatment plan.

PMID- 15159831
TI  - [Proteolytic phenomenon in enamel caries]
AB  - The proteolytic phenomenon in enamel caries has been investigated from three
      directions.Three kinds of proteolytic enzymes,papain,trypsin and collagenase have
      been used for treating enamel both in vitro and in vivo to observe their effect
      on the development of artificial enamel caries and demineralization of upper
      central incisors of thirty young persons.The results showed that the depth of the
      artificial caries was not increased after enzyme treatment.The calcium content of
      the demineralizing solution is also not increased after enzyme treatment.when the
      enamel powder of human beings was treated at first by natural plaque fluid and
      then by demineralizing liquid,no difference was observed between the data of
      experimental and control groups.Therefore,the results of this study does not
      support Gottleib's proteolytid theory of caries,especially in case of enamel
      ones.

PMID- 15159833
TI  - [Application of Calvital pulp capping in deciduous teeth]

PMID- 15159832
TI  - [Histolgical and immunohistochemical study of malignant myoepithelioma of
      salivary glands]
AB  - Histological and immunohistochemical features of 12 cases of malignant
      myoepithelioma of the salivary glands were studied.There were 4 major histologic
      types in the tumor tissues:(1)clear tumor cells proliferated mainly with or
      without keratin peral;(2)spindle shaped tumor cells proliferated mainly with or
      without mucoid regions;(3)plasmacytoid(hyaline) tumor cells were arranged in
      adenoid configurations.In the immunohistochemical studies,the tumor cells were
      positive for actin;myosin;glial,fibrillary,acidic,protein.(GFAP);S-100 protein
      antibodies.The authors consider that the application of the above-mentioned
      antibodies may assist in the differentiated diagnosis of malignant myoepithlioma.

PMID- 15159834
TI  - [On the educational aspects of esthetic stomatology]

PMID- 15159835
TI  - [Maxillary sagittal fracture: Analysis of 16 patients]

PMID- 15159836
TI  - [Predication of the prognosis of patients with tongue carcinoma]

PMID- 15159837
TI  - [Treatment of sublingual cyst with 5% sodium morrhuate: Reportof31 cases]

PMID- 15159838
TI  - [Use of maxillary complete denture with proglossis occlusion in patients with
      atrophied mandibular alveolar ridges]

PMID- 15159839
TI  - [Comparison of three commonly used local anesthetics in dentistry]

PMID- 15159840
TI  - [Changes of serum Potassium in patients with oral and maxillofacial neoplasms
      after operation]

PMID- 15159842
TI  - [Lichen like lesion of the oral mucosa caused by amalgam filling: Report of one
      case]

PMID- 15159841
TI  - [Tuberculosis ulcer of the oral mucosa: Report of 3 cases]

PMID- 15159843
TI  - [TNM staging and classification for malignant tumors: II. Head and neck cancer]

PMID- 15159844
TI  - [Ductal exfoliated cytology in the practice of mumps]
AB  - The author used smear from Stensen's duct aspiration to observe exfoliated
      cytology in order to help diagnosis of early mumps.According to the smears from
      100 cases of mumps and other 50 cases of bacteria parotitis and/or normal parotid
      as contro,the author revealed that if there are a lot of ductal epithelial
      cells,monocytes and polynuclear cells,monocytes and polynuclear phagocytes at
      same time,it could give diagnosis "Mumps" to that patient.In control group,it is
      unable to observe those three kind cells at same time.The author also discussed
      the mechanism of how would these three kind cells appear in mumps in accordance
      with references.

PMID- 15159845
TI  - [Giant mandibular second molar: Report of one case]

PMID- 15159846
TI  - [A comparative study of masticatory efficiency between partial denture wearers
      having one remaining tooth and complete denture wears]
AB  - Masticatory efficiency is one of the important indexes of judging masticatory
      function after dentures restored.The aim of this study was to measure and analyze
      masticatory efficiency of partial dentur wearers having one tooth left and
      complete denture wearers,by using a method of measuring msticatory crushed
      granules.The results showed that the crushed granules for partial denture wearers
      with one remaining tooth were smaller than that for complete
      ones.Therefore,partial dentures with a few remaining teeth were better than
      complete ones on effects.

PMID- 15159847
TI  - [Observation of clinical effect of bioactive glass titanium alloy core implant]
AB  - A novel kind of implant made of titanium alloy spray coated with a suitable
      bioactive glass was investigated.49 implantation were done in clinical patients
      from Oct 1988 to 1992.42 implantation functioned well up to the time.7
      implantation failed. The success rate is 85.71%.The authors have also discussed
      the indications,method of implantation and other related things on the paper.

PMID- 15159849
TI  - [Ameloblastocarcinoma: Report of one case]

PMID- 15159848
TI  - [The diagnosis and the treatment on lingual thyroid]
AB  - Lingual thyroid is a rare example of ectopic thyroid.This paper reported three
      cases of lingual thyroid(all female,aged between 16 and 61 years) were discussed
      with diagnosis and treatment.A transoral excision using the median total
      glossotomy and precervical excision was performed through a transsuprahyoid
      approach.Postoperative complications is not developed.The approach above mention
      is better than that of median labiomandibular glossotomy.

PMID- 15159850
TI  - [The pathological changes of lip biopsies and dental caries on Sjogren's
      syndrome]
AB  - This paper showed that in 110 cases of Sjogren's syndrome(SS),the caries
      incidence was high and was related to the salivary gland lesions.In comparison
      with 90 matched no SS group,the incidence of caries in SS was 88.18%,and in no SS
      group 73.33%(P<0.01).The average of caries in cases with more than ten
      inflammatory foci were significantly increased than in those less than ten,no
      significant difference in the average of caries was observed between primary and
      secondary SS.The amounts of salivary excretion measured were significantly
      decreased in 30 cases with SS than in no SS group cases,and the more the
      inflammatory foci,the less the salivary excretion.

PMID- 15159851
TI  - [The cytotoxicity of Sne-Pack periodontal dressing and scanning electron
      microscopic study]
AB  - We prepare a non-eugenol periodontal dressing Sne-pack(Sp),then investigated the
      effects of cess cytotxicity and observed the surface of materials on scanning
      electron of materials on scanning electron microscopy.The comparison results with
      Coe-pack (Cp) and zinc oxide-eugenol(Ce)showed that three materials have
      inconsiderable toxic effect on L-929 cell,the Sp and Cp dressing are smoother
      than Ce.

PMID- 15159852
TI  - [The relationship between loading on the TMJ and occlusal splints]
AB  - The primary purpose of this study is to estimate loading conditions on the TMJ
      with five different occlusal splint.We developed a model that simulated dynamic
      relationship between dental occlusion,masticatory muscles and TMJ.It is
      demonstrated that loading on the condyle increases whatever kinds of splints are
      used.The anterior splint brings about larger loading on the condyle than any
      other splint.When the ratio force of the muscle on the non pivot is1,left-side
      pivot split makes loading on left condyle decrease and right increase.It was
      change on both condyles when posterior teeth are missing including loading,
      contact and unilateral mastication.

PMID- 15159853
TI  - [The fabrication technique of Plat casting ceramic prosthesis: A preliminary
      study]
AB  - Microspectrophotometer and transmitted electron microscope (TEM) were used to
      study the change of DNA synthesis and ultrastructure after fibronection(FN) acted
      on cultured periodontal ligament cells (PDLC).The results showed that the data of
      nuclus area,nuclus total absorbs and nuclus mean absorbs of PDLC in FN group was
      higher than control(P<0.01).Under the TEM we observed that in FN group there were
      more euchromatin in cell nuclues and more organ cells such as
      microfilaments,chondriosomes and endoplasmic reticulum in cytoplasm.It suggested
      that FN can accelerate periodontal regeneration by promoting DNA and protein
      synthesis of PDLC.

PMID- 15159854
TI  - [Pleomorphic adenoma of the mandible: Report of one case]

PMID- 15159855
TI  - [Clinical survey of dental wedge-shaped defects in 924 staffs]

PMID- 15159856
TI  - [Replacement of complete denture: Technical note]

PMID- 15159858
TI  - [Prevention of dry socket with norfloxacin gelfoam : Report of 5 cases]

PMID- 15159857
TI  - [Chondrosarcoma in oral and maxillofacial region: Report of 17consecutive cases]

PMID- 15159859
TI  - [Kimura  s disease of the mandible: Report of 9 cases]

PMID- 15159860
TI  - [Restoration of teeth defects with light curing composite resin: Analysis of
      failure causes]

PMID- 15159862
TI  - [Mixed tumor of the salivary gland: Clinical analysis of 198cases]

PMID- 15159861
TI  - [The tongue images in oral cancer: Analysis of 100 cases]

PMID- 15159863
TI  - [Diagnosis and treatment of malignant tumors of the salivary gland]

PMID- 15159864
TI  - [The development of oral health care in Shanghai schools: re-examination]

PMID- 15159865
TI  - [CT diagnosis of parapharyngeal neoplasms and selection of surgical approaches]

PMID- 15159866
TI  - [Factors influencing alveolar ridge absorption and atrophy of the mandible(review
      article)]

PMID- 15159867
TI  - [The commonly used English abbreviations in stomatology and their significance:
      I. Stomatological associations and organizations]

PMID- 15159868
TI  - [TNM staging and classification for malignant tumors: I. General considerations]

PMID- 15159870
TI  - [A study of the reasonable vertical thickness of stabilization splint]
AB  - It was proved in this study through the measurement and calculation of the shape
      and size of dentition and jaws and the position of the hinge axes that the
      thickness of stabilization splint was difficult to be confirmed within free way
      space, it was therefore suggested that attention should be paid on forming a flat
      and smooth occlusal plane during the design and manufacture of splint, so that
      the points to a flat plane contact relation could be presented between the split
      and the tops of working cusps. Guidance effect on inclines must be eliminated.
      The thickness of splint should depend upon the height of cusp and the overbite
      degree of the patient, so that free way space wasn't absolutely inviolable in the
      set of stabilization splint.

PMID- 15159869
TI  - [Using Metronidazole and Hydroxyapatite for preventing dry socket after
      extraction of impacted mandibular 3rd molar]
AB  - Dry socket is one of the most frequent complications after teeth
      extraction,especially in impacted mandibular third molars.The etilogy and
      prevention is not clear.This study id based on principles of clinical
      epidemiology.Randomized double-blind method was carried out in 549 patients to
      test the value of the prophylactic use of Hydroxyapatite,to test the value of the
      prophylactic use of Hydroxyapatite and Metronidazole,placed in the sockets of
      extracted impacted mandibular third molars.The results of the incidence of DS was
      7.1% of Metronidazole treated sockets,and 2.1% of Hydroxyapatite treated
      sockets,It is concluded that Hydroxyapatite is an effective preventive factor for
      dry socket,The possible mechanism of Hydroxyapatite and the dry socket etiology
      were discussed.

PMID- 15159871
TI  - [A comparative study of velopharyngeal function after palatoplasty with different
      age group]
AB  - That the most suitable age of palatoplasty is still an argumentative question.The
      final purpose of palatoplasty is to obtain the satisfactory effectiveness is to
      obtain the satisfactory effectiveness of phonetic distinctness.So,early
      palatoplasty is suported by more more experts and patient's parents.This study
      detected 60 cases velopharyngeal function after traditional palatoplasty with two
      flaps,adopting nasopharyngeal fiberscope and detective system of image processing
      and quantitative analysis of velopharyngeal function,for long term evaluation of
      traditional palatoplasty with different operative success iin early palatoplasty
      group (less than 3 years old) was 80.0% while that in later palatoplasty group
      (more than 6 years old) was 53.3%.From other aspects of types of velopharyngeal
      competence,mobility of soft palate and rate of velopharyngeal coronary
      contraction,the author described advantages of early palatoplasty.

PMID- 15159873
TI  - [Application of eye spring in correction of the malposed canine]

PMID- 15159872
TI  - [A discussion of jaws relation in complete denture restoration]
AB  - We studied jaws relation of 8 edentulous patients after complete denture
      restoration by using Digital Sirognathograph (D-SGG).The results indicated that
      the maximum intercuspation occlusion (i.e.CO or MCP) is not commonly coincident
      with the CRO,and the discrepancy is statistically significant.The CO is anterior
      to the CRO by 0.72+/-0.39mm,and it may vary significantly in different closures
      of the same patient. This implies that the termination of the occlusion with
      neuromusculature is not strictly precise and constant,but alters in a
      corresponding range.So,it seems reasonable to develop a "freedom of centric" in
      the range of 0.72+/-0.39mm anterior to the CRO.The physiological functional
      occlusion,therefore,is restricted to neither of the CO nor the CRO, but is guided
      between the two.

PMID- 15159874
TI  - [Clinical analysis of tooth fracture trauma by masticatory occlusion]
AB  - About 185 tooth fracture cases among 184 patients,it was found that tooth
      fracture happened on misticatory occlusion almost follows the regulation at the
      same tooth which has suffered of damage,such as dental caries,wedge shaped defect
      and cracked tooth and so on.The position of tooth damage is that of tooth
      fracture as well.The range and extent effect obviously on the tooth fracture.The
      terminal point of fracture line is related closely to pulp condition.It's
      considered that the out force is the major direct cause of tooth fracture,while
      position,extent,range and pulp condition before fracture is the main inner
      inducement fact.

PMID- 15159875
TI  - [Verapamil enhancement of antitumor activity of mitoxantrone on ACC-22 cells in
      citro]
AB  - The combined effect of verapamil and DHAD on the growth of human adenoid cystic
      carcinoma cell line(ACC-2) in vitro was investigated.In combination, VP and DHAD
      had synergistic inhibitory effect.VP enhanced the cytotoxicity of DHAD in ACC-2
      cells and significantly inhibited the cell proliferation.VP also potentiated the
      inhibitory effect of DHAD on colongenic ability of ACC-2 cell,suggesting it
      enhance the cytocidal effect of DHAD on human adenoid cystic carcinoma.

PMID- 15159876
TI  - [The application of Immuno-gold and silver stainning to detecting OLP and DLE]
AB  - Immuno-gold and silver staining (IGSS) is an advanced labelling method followed
      by Immuno-fluorescence(IF),Immunoenzyme and Radio-immunity.In this study,the IGSS
      method for detection of deposits of Immunogloblins (IgG,IgA,IgM) at the BMZ had
      been performed on biopsy specimens from oral lesion of patients with OLP and
      DLE.The results indicated that the sensitivity and specificity of IGSS were super
      than that of DIF.It suggested the IGSS be an available method to detect oral
      mucosal diseases widely.

PMID- 15159877
TI  - [Indirect testimony of stress conduction from mandible to skull in maxillofacial
      trauma: morphological changes of temporomandibular joint disc]
AB  - There were cerebral injuries accompanied in maxillofacial high velocity
      projectile wound.Owing to the special anatomic relationship between skull and
      facial bones,the stress conduction of bone was an important factor of cerebral
      injury in maxillofacial wound.In this experiment,the canine mandibular regions
      were wounded by steel spheres,which weight 1.03g,impacting velocity at 1400m/s,to
      produce severely maxillofacial firearm wounds.The morphological and pathological
      changes of temporomandibular joint disc of wounded side were observed with light
      and electron microscopes.The microscopic injuries of disc,including arrangement
      disorder of figre,spotty edema and some fibrous dissolution,etc,were found.These
      results have provided an indirect evidence of injurous mechanism of the cerebral
      injury accompaning maxillofacial high enery misslle wound.

PMID- 15159878
TI  - [Experimental study on the Biomaterial/Porous Titanium composite dental implants]
AB  - This study investigated the tissue compatibility of bone morphogenetic protein
      (BMP) /biologic ceramic/porous titanium implant,BMP/porous titanium
      implant,biologic ceramic/porous titanium implant and porous titanium implant by
      LM,SEM,EDXA.The results showed that the new bone formation and new bone mature
      were earlier in the BMP composite implants treated group.BMP uncomposite implants
      had no evident difference in the time of new bone formation, but the interface
      bonding ways had significant difference.

PMID- 15159879
TI  - [The appliance of image analysis in the diagnosis of oral Lichen Planus and it's
      malignant change]
AB  - After the Feulgen dying,if the normal oral mucous,oral Lichen planus as well as
      the pathological cut sheets with atypical dysplasia and malignant change in
      defferent degrees,use the image analysis technique to measure the morphologic
      parameters of the nucleus(including nuclear surface area,perimeter maximum
      nuclear diameter,minimum nulear diameter,equivalent circle diameter,morphological
      factor) and the amount of DNA,5CER acts as an indes of distinguishing malignancy
      or benignancy,the value of 5CER in malignant is more than 10% and in benignant is
      less than 10%.The result of the analysis from the optical microscope differs from
      the optical microscope differs form the image analysis.There are so many personal
      factors in the qualitative analysis by optical microscope that it because quite
      imperative to research for a new diagnosing way.The synchronization of
      quantitative analysis and qualitative analysis can correct the personal errors in
      qualitative analysis.It will be very useful for directing the clinical practice
      and the judgment of prognosis.

PMID- 15159880
TI  - [The biologic character of gingival fibroblasts from normal and periodontitis
      sites]
AB  - Histological and clinical studies have found that periodontal ligament
      fibroblasts can produce connective attachment,while gingival fibroblasts cannot
      yet.The mechanism for gingival fibroblasts losing their ability of new attachment
      is unknown.We investigated the function of colagen synthesis by gingival
      fibroblasts from periodontitis sites,and normal sites and their response to TGF
      beta,and Nicotinamide and Lactate,the inhibitors of poly(ADP-ribosyl)ation.We
      found that gingival fibroblasts from diseased sites produce much less collagen
      than from control sites (73.6+/-8.8vs.107.1+/-12.3,P<0.01),and these cells show
      unresponsive to TGF-beta,Nicotinamide and Lactate on collagen synthesis.These
      results may partly explain why gingival fibroblasts from periodontitis site lose
      their ability of new attachment.

PMID- 15159881
TI  - [Application of low temperature demineralization and frozen section technique in
      the immunochemistry study of dental pulp]
AB  - The purpose of the study was to explore experiment method by means of periodate
      lysine-parafoemaldehyde fixative,EDTA low temperature demineralization and frozen
      section technique.The results showed the technique suit either completely to
      immunohistochemical study of the pulp matrix and of the cell surface expression
      that was weaker antigenicity,or to enzyme histochemical staining of the dental
      pulp.

PMID- 15159882
TI  - [On the essentials of esthetic stomatology]

PMID- 15159883
TI  - [Advances in root canal sealers]

PMID- 15159884
TI  - [Oral pemphigus vulgaris: Report of 12 cases]

PMID- 15159885
TI  - [Giant mass of the mandible: Clinicopathologic conference]

PMID- 15159886
TI  - [Repair and refabrication of removable denture]

PMID- 15159887
TI  - [Introduction of a simple and practical ruler for cephalometric analysis]

PMID- 15159888
TI  - [Oral mucosal hypersensitivity caused by iodine during disinfection: Case report]

PMID- 15159889
TI  - [Self made pocket saliva suction and its application]

PMID- 15159890
TI  - [Velopharyngeal incompetency: An overview]

PMID- 15159891
TI  - [Analysis of malignancy change of oral leukoplakia]
AB  - 235 cases of oral leukoplakia.which was confirmed histologically,had been
      observed and followed-up for 1-16 years.32 cases of them were malignancy
      changed,The incidence was 13.6%.The ratio in 18 male cases was 11.8% and 14.9% in
      female ones.The mean age of malignancy changing group was 53.4 years.The higher
      maligancy changing rate was shown in the granulation type and verrucous form
      type.The more often involved site was the tongue and the incidence was
      75%,especially in the border and dorsal of the tongue.This study suggested that
      the pain display,local congestion,macule,the enlargement of the.esion
      proliferation,ulceration and firm of the mass were all the bodements of
      malignancy change.In this paper total 32 cases were followed-up 2 cases got
      recovery,the prognosis was good.

PMID- 15159892
TI  - [Study on the relationship between congenital toxoplasmosis and monsters of cleft
      lip and palate accompanied by multiple malformation]
AB  - Toxoplasomsis is a zoonotic disease resulted from toxoplasma infection,This paper
      reports ten monsters that suffered from congenital cleft lip and palate
      accompanied antigens(RCEP,COA test) were positive.Toxoplasma antibodies
      (IHA,IFA,RIPEGA test) in mothers' serum were also positive.Microscopic
      examination revealed toxoplasma trophozoites and pseudocysts in the tissue of
      cleft lip and palate as well as viscera.In addition,We used SPA method to reveal
      toxoplasma in the tissue.We indicate that toxoplasma infection of pregnant women
      is one of the cause of monsters.It is the important biological factor and closely
      related to eugenics.Stomatologists must pay attention to this etiology.

PMID- 15159893
TI  - [Immune status of oral lichen planus and squamous cell cancer patients-T subgroup
      cells evaluation in PBL]
AB  - The levels of T-subgroup cells for 30 oral lichen planus(LP) and 25 cancers are
      reported.15 health are constracted.The results are as follows:Health OKT value
      T(3) 62.8+/-1.81,T(4) 44.4+/-7.34,T(8) 25.5+/-0.71,T(4)/T(8) 1.79+/-0.13;OLP OKT
      value:T(3) 53.2+/-1.92,T(4) 40.2+/-1.9, T(8)38.61+/-2.2, T(4)/T(8) 1.10+/
      0.07,Cancer value 52.9+/-1.9,40.2+/-2.3,36.4+/-2.05,1.17+/-0.09. Both group of
      patients were compared with health.The level of OKT(3) OKT(4)/OKT(8) was
      decreased significantly(0.001),but OKT(8) qA increased significantly(0.001).This
      shows that T cell immune function is decreased in the oral LP and cancer
      patients.

PMID- 15159894
TI  - [Clinical evaluation of manual and ultrasonic subgingival scaling using image
      analysis]
AB  - The objective of this study was to compare the effect of hand and ultrasonic
      instrumentation in removing subgingival plaque and calculus.In experiment
      one,forty-eight teeth from patients were randomly assigned to be scaled with
      curettes or ultrasonic scaler.Probing depth,clinical attachment level and
      bleeding index were reexamined 2 months latter.The results demonstrated that no
      significant differences between the two mehtods.In experiment two,seventeen teeth
      from six patient were also randomly scaled manualty ultrasonic or uninstrumented
      as a control.All these teeth were extracted immediately after subgingival
      scaling.The proportion of tooth surfaces covered by residual plaque and
      calculus(relative to the total surface area of the side of the tooth)was analysed
      on each tooth using computerized graphic processing.The findings showed the
      proportional areas of residual plaque and calculus in teeth.But the hand scaled
      root surface were much smoother than those treated with ultrasonic scaler.

PMID- 15159895
TI  - [The research of orthodontic therapy in second molar overjet]
AB  - The malocclusion of overjet of second molars is very frequent,When the 2183
      patients were examined,we found that the above-mentioned malocclusion had 420
      cases.It accounts for 19.22%.The factors led this malocclusion are many.The cases
      of buccoversion of second molar in maxilla and normal of this tooth in mandible
      are 257.That upper second molar is buccoversion and lower second molar is
      linguoversion.all in one side,are 104 cases.Upper normal and lower linguoversion
      are 24.Buccoversion of two second molars only in upper dental arch and lingual
      position of second molar in one side of lower dental arch are 31.Even that
      bilateral lower second molars are linguoversion and this tooth of upper jaw in
      one side is buccoversion are 4.Therefore,we must adopt various technique
      according to malposition condition of second molar.This paper will describe five
      corrective.

PMID- 15159896
TI  - [Clinical anti-caries effect of dentifrice containing two fluorides]
AB  - Anti-caries effect of dentifrice containing sodium monofluorophophate and sodium
      fluoride was studied among 2-3 years OLD nursery children.After one year,both
      mean dft and dfs were very significantly lower than those of control groups.

PMID- 15159897
TI  - [Application of the "Wits" approsal in Shanghai children with normal mixed or
      early permanent dentition]
AB  - 128 children in Shanghai with normal mixed or early permanent dentition were
      selected in this servey to gain their normal value of the "wits" approsal.The
      results showed (1) there was no significant difference of "wits" approsal between
      the two groups of the children. (2)There was no disparity in "wits" approsal
      ofthe children with the same nationality and living in different regions. (3)
      There was a little change in value of the "wits" apporsal during the growth
      period or the children,which indicated a comparative identical relationship
      between the upper and lower basal bone.This study suggested that the application
      of the "wits" approsal be very imnportant in orthodontic clinic because of its
      expressing exactly the relationship of the jaws.

PMID- 15159898
TI  - [Effect of anhydrous glycerol injection into the mental foramen of rabbit on
      inferior nerve:An experimental study]
AB  - In this experiment anhydrous glycerol was injected into the mental foramen of
      rabbits to determine neurolytic effects on the peripheral trigeminal nerve by
      electrohysiologic and morphologic methods.The rabbits underwent unilateral
      injection of anhydrous glycerol and the control side was injected with normal
      saline.The results show that partial fibers are effected (myelinated and
      unmyelinated fibers at random).Glycerol injection increased the average latencies
      and reduced the average amplitudes of compound action potentials.Morphologic
      examination disclosed myelin swelling,disintergrationan d axonal
      shrinking,axonolysis.One week after the injection,eletrophysiologic and
      morphologic changes were most severe and signs of regeneration were noted in the
      fifth week,By 16 weeks after injection,the nerve fibers appeared almost normal.

PMID- 15159899
TI  - [Stress analysis for the abutments and the supporting alveolar bone in semi-fixed
      bridge]
AB  - This research was made in a mandibular that simulated dynamic relationship
      between occlusion,masticatory muscles and TMJ and that has full and normal teeth
      excepting the right second premolar was lost.This study measue?red and analysed
      the stress distribution and changing in the abutments and the supporting alveolar
      bone with strain gauge when the edentulous are was restored by T-type attachment
      and rest type connectors semifixed bridge.The results suggested that:(1)The
      stress of the abutment and alveolar bone increased by prematurity and it's
      distribution and changing were different according to the place of prematurity
      and type of the connectors.(2) T-type connecter has stress broken action and rest
      connector hasn't obvious such an action when prematurity of central occlusion.

PMID- 15159900
TI  - [Catch up and follow up of natal teeth: report of 6 cases]
AB  - 6 cases with natal teeth were found in 11930 live births.5 cases, in which eight
      natal teeth had been found, also had been followed-up for 38-54 months after
      birth and five crownless root-like mass were found in 4 cases out of 5 at the
      site where natal teeth had been extracted at the time of birth. The histological
      study was made in one natal teeth and one root-like mass.

PMID- 15159901
TI  - [Culture of the sheep TMJ synovial cells in vitro-notes on cellular arrangement
      and ultrastructural feature]
AB  - The sheep TMJ synovial cells were cultured in virtro by tissue explantation.and
      the phase-contrast microscopic and electron microscopic examinations were
      made.The synovial cells in which they were arranged in a unique manner.It is
      suggested that the ultrastructural characteristics of the synovial cells in vitro
      can serve as the basis of cell-type classification.

PMID- 15159902
TI  - [Isolation of Neisseria from human dental plaque and study of characteristics of
      acid degradation]
AB  - The Neisseria was isolated and identified from human dental plaque.The incidence
      of Neisseria was 100%.The N.Sicca was the predominant group.The results of sugar
      metabolism of Neisseria indicated that they were not only able to produce acid
      while sugar was offered sufficiently,but also degrade lactate evenacetate to
      supply energy after sugar was consumed.

PMID- 15159903
TI  - [The study of stratification curing and adhesion of light curing composite resin]

PMID- 15159904
TI  - [Study of lipoteichoic acid in G+ bacteria  II. The adhesive effect of
      lipoteichoic acid produced by Streptococcus mutant]

PMID- 15159906
TI  - [Study of dental fluorosis: An overview]

PMID- 15159905
TI  - [Diagnosis and treatment of brachial syndrome]

PMID- 15159907
TI  - [Metathesis and infusion of carbamide fluid: A simple method for cystic lesions
      of the head and neck]

PMID- 15159908
TI  - [Successful replantation of a contaminated tooth exsomatized 14 hours with vital
      pulp: Report of one case]

PMID- 15159909
TI  - [Dislocation of the temporomandibular joint caused by inderal: Report of one
      case]

PMID- 15159910
TI  - [Management of postoperative hemorrhage after cleft palate repair using water
      cyst filled into the posterior nasal nostril]

PMID- 15159911
TI  - [Management of bite injury of the human tongue by snakes]

PMID- 15159912
TI  - [The research and analysis on the fused primary teeth regarding to the permantent
      dental dentition-10 years follow up]
AB  - 36 cases with unilateral mandibular fused primary teeth have been followed up and
      analysed for 10 years.The result showed that the fused primary teeth obviously
      affect the secondary permanent teeth and permanent dental dentition.In this
      series,there was one secondary permanent tooth lost in all of 19 cases.The
      secondary permanent tooth was also fused tooth in 3 cases.The length of permanent
      dental dentition and the width of dentition in front of the second cuspids in the
      cases with one secondary permanent tooth lost were extremely shorter than that in
      the cases with secondary permanent teeth.In addition,the mandibular dental
      dentitions were towards the fused teeth side.Comparing to the synonymic teeth,the
      mesial and distal steps and the height of secondary permanent teeth of fused
      primary teeth were no difference from normal side.

PMID- 15159913
TI  - [Acute side effect of postoperative radiotherapy in malignant head and neck
      neoplasm]
AB  - From August 1989 to May 1991,160 patients with malignancies of the head and neck
      region were treated by surgery and postoperative radiotherapy.Seventy seven
      patiens underwent resection of the primary lesion combined with neck dissection
      and 83 patients had resecton of the primary lesion only before radiotherapy.After
      irradiation 33.8% (54/160) patients developed edema in face and
      neck,13.1%(21/160) patients developed headache.The style of neck dissection
      (unilateral,bilateral or no neck dessection) did significantly influence the
      rates of the acute side effect(P<0.01).The interval between surgery and
      radiotherapy and radiation dose were not important influential
      factors(P>0.05).The clinical manifestations,possible mechanism and prevention of
      the acuter side effect is presented.

PMID- 15159914
TI  - [Analysis of 526 cases of trigeminal neuralgia treated by radiofrequency thermal
      coagulation of temperature]
AB  - In 526 cases of trigeminal neuralgia,254 cases were male,272 were female.The age
      from 17-90,average age is 58.8. The shortest course of disease is 2 months,but
      the longest one is 39 yrs,with a mean course of 6.8 yrs.Pain in right side is
      more than in left side.Pain was more often involved simultaneously on first and
      second branch of trigeminal nerve.505 cases (96%)got the complete response after
      radiofrequency thermal coagulation therapy,13 cases (2.47%) were obviously
      advanced,while 8 cases (1.52%) were failed.The total effective rate was
      98.47%.After follow up of 1-5yrs,in 518 efficacious cases,65 recurred cases
      (12.54%) were treated again by the same method,pain was then stopped.

PMID- 15159915
TI  - [The application of removable partial denture with telescope crown retention]

PMID- 15159917
TI  - [Desmoplastic fibroma of the jaw: Report of 2 cases and review of the literature]

PMID- 15159916
TI  - [The causes of misdiagnosis of periapical diseases and subsequent management]

PMID- 15159918
TI  - [A study on resorbable local metronidazol delivery devices]
AB  - A local metronidazol (MTZ) delivery using resorbable base material was studied.
      In vitro MTZ was almost completely released within 24 hrs from the
      hydroxypropylmethyl cellullouse(HPMC) strips.In vivo,release of the drug strips
      was also measured in six patients who had deep pockets of more than 5mm.MTZ
      containing HPMC strip was inserted in the pocket.The average amount of MTZ in the
      gingival crevicalar fluid(GCF) 24 hrs after insertion of strip was
      40microg/ml.(much higher than the reported MIC of some microorganisms associated
      with adult periodontitis).In vitro there were significant inhibitory effects of
      MTZ containing strips on the microorganisms associated with periodontal
      disease.The prevalence of spirochetes and motil rods,and gingival index(GI) was
      remarkably reduced in the MTZ administered pockets,It is suggest that this new
      direct drug delivery system with HPMC used as base material could be used to
      treat periodontal disease.

PMID- 15159919
TI  - [The morphologic study of the dental arch in Shanghai children at prepermanent
      teeth stage: The size of the lower dental arch and the relation between the upper
      and lower dental arch]

PMID- 15159920
TI  - [Immunologic and microcirculational study of oral lichen planus with Xu Zheng and
      Shi Zheng]

PMID- 15159921
TI  - [The effect of EBCI Iontophoresis on orthodontic tooth movement in rabbits]
AB  - The purpose of this study was to observe the effect of EBC ionophoresis on
      increasing the rate of tooth movement in rabbits.21 rabbits,in whose lower
      incisors the standard orthodontic appliances were placed,were divided into 3
      groups at rendom which separately received iontoporesis of EBC,iontophosesis and
      injection of physiological saline at the submucosal area of the lower
      incisors.The results showed that the animals with EBC iontophoresis obtained
      tooth movement rate of 4.275+/-0.1214(mm) and the animals with NaCl iontophoresis
      and injection were respectively 3.337+/-0.4626(mm) and 2.178+/-0.2922(mm).The
      histological observation had also found the evidence of the ability of EBC to
      stimulate osteoclasts in preiodontal pression side and osteoblasts in
      tension.This study suggested that iontophoresis of EBC could play an important
      role in reconstructing the periodontum and speeding the tooth movement in
      rabbits.

PMID- 15159922
TI  - [Chemical analysis of lipopolysac-charides derived from oral anacerobes]
AB  - Lipopolysaccharides were isolated from six oral anaerobes(Va.Bg.Bf.Fn.Aa.Co.)by
      the hot phenol-water procedure and purified by PCP method.The six species can be
      all extracted their LPS with different yields (from 0.70 to 2.83% of cell dried
      weight).Comparable of LPS with the enterobacteriaceae(Sm.),they were the
      constructed with hexosamine,fatty acids and phosphorus etc.On the other hand,they
      showed much distinct differences from the enterobacterial LPS structure as
      follow:(1) 2-keto-3-deoxy-D-mannooctonate(KDO) was not detected by routine
      procedure.(2)The amount of heptose is reltively lower.(3) Methylated and branched
      fatty acids were detected.These chemical characteristics may relate to biological
      activities and pathogenic potential of LPS and bacteria themselves.

PMID- 15159923
TI  - [The antitumor effect of DNL/rIL-2 and Pingyangmycin on human tongue
      carcinoma(Tca 8113) transplanted to Nude Mice]
AB  - We have tried to find out if the combination of DNL/rIL-2 and antitumor drug is
      able to induce a synergistic increase in the antitumor therapeutic effect.DNL
      were obtained from the patients who suffered from primary tongue cancer were been
      performed operation of radical neck dissection.When the ratio of the effectors to
      the targets was 5:1 with local administration,rIL-2 5x10(5)Kg/d and PYM 5mg kg/d
      ip administration,the inhibitory rate of tumor growth was 86%.The results showed
      a significant rate increase when compared with the therpeutic effect obtained by
      DNL/rIL-2,or PYM alone (P<0.05).In addition,we used Burgi formula to evaluated
      the antitumor effect of DNL/rIL-2 combined with PYM.The q value was 1.46.These
      results suggest that immunotherapy and chemotherapy perhaps function
      synergistically.

PMID- 15159924
TI  - [The high resolution acoustic images of tumors of the salivary gland]

PMID- 15159925
TI  - [Effects of low level fluoride on the resolutive behavior of dental enamel]
AB  - The purpose of this investigation was to study the low level fluoride on the
      resolutive behavior of dental enamel in vitro.Twelve enamel slabs were used to
      treat with acidulated phosphate fluoride solutions containing different F
      concentration and then with acidic artificial carious gel.Chemical analysis were
      carried out with atomic absorption spectrophotometer,fluoride ion-selective
      electrode and electron microprobe.Results indicate that different F concentration
      in environmental solutions make different physicochemical ways on effects to
      enamel demineralization,they are specific and non-specific absorption of fluoride
      ions or dissolution and reprecipitation of fluoridated apatite and CaF(2).

PMID- 15159926
TI  - [Comparative study on healing process between vascularized and non-vascularized
      autogenous bone grafts]
AB  - This study made a histological comparison (light microscope and transmission
      electron microscope) between vascularized bone graft (VBG) and non-vascularized
      bone graft (NVBG) in mandible of dog.The study showed:the healing process of VBG
      was the same as that of bone fracture.The "creeping substitution" process of NVBG
      was imbued with the inflammation induced by dead bone.There was no significat
      difference on the bone union between VBG and NVBG perhaps for the recipient
      region was better vascularized.

PMID- 15159927
TI  - [On root canal therapy]

PMID- 15159928
TI  - [Study of lipoteichoic acid in G+ bacteria  I. Biologic and immunologic nature]

PMID- 15159930
TI  - [The study of influencing cellular dynamics of gynostemma pentaphyllum on golden
      hamster cheek pouch premalignancy]
AB  - Studying premalignancy is an important field of conquering cancer.The aim to
      study the mechanics of oral mucosal premalignant formation and seek effective
      drug which could prevent and block cancer,Gynostemma Pentaphyllum(GP) was applies
      to block carcinomatous conversion of golden hamster cheek pouch by Salley's
      way.Using light microscopic observation and proliferating cell nuclear
      antigen(PCNA) as well as bromodeoxyuridine(BrdU)(PCNA AND BrdU are
      immunohistochemistry techniques),GPs effect was observed dynamically.We found
      that GP could delay the presence of leukoplakia and decrease the rate of presence
      as well as cancer-causing rate. The positive cells of taking drug group PCNA and
      BrdU were lower than model group significantly and in a lower condition all the
      time.It is illustrated that GP has the effect of preventing cancer and inhibiting
      cellular dysplasia.

PMID- 15159931
TI  - [Measurement of the three dimensional shape about crown with the digital speckle
      correlation method]
AB  - It is the first step that the data about relative teeth's shape are catched for
      CAD/CAM system in dental rehabilitation.That is how to measure the teeth's
      shape.The digtal speckle correlation method are introduced to measure the teeth's
      shape in the article.For one posterior tooth,we measured the five surfaces that
      the occlusal surface and the four axial surfaces.According to some special
      marks,we changed the five group's local data into one coordinate and
      reconstructed the three dimensional shape of the tooth.At last we drew the graph
      with the computer.In this paper the author also discussed some factors about the
      measure system's sensitive and precise and the extent scale.etc.

PMID- 15159929
TI  - [Interstitial tubercle in Chinese and Japanese young adults]
AB  - A comparative study on the incidence of interstitial tubercle from standardized
      stone casts of 160 Chinese and 190 Japanese young adults,ages from 20-30.The
      following results were obtained:(1)No significant difference in the incidence of
      interstitial tubercle on maxillary first premolar between Chinese and Japanese
      groups(P>0.05),but on maxillary second premolar,Japanese is higher than
      Chinese(P<0.05).(2)The incidence of interstitial tubercle on maxillary first
      premolar is higher than second premolar in two groups(P<0.05).(3)The intestitial
      tubercle occurs in unilateral more frequently than in bilateral.The incidence of
      maxillary first premolar in mesial of occlusal is higher than in distal.No
      difference between mesial and distal on occlusal of maxillary second premolar in
      the Chinese group,and the incidence in mesial is higher than in distal in the
      Japanese group.

PMID- 15159932
TI  - [Research on hydrokinetics of self-intermittent vaccum root canal drainage]
AB  - A hydrokinetically simulated sucking was made to study the self-intermittent
      vacuum drainage of the root canal.Results showed that due to the shape difference
      between diameters at the upper and lower parts of the canal,the high-speed air
      flow at the lower-end opening can drain the fluid below the opening out while the
      lower-speed air-flow at the upper opening is not likely to make the saliva and
      see page in the oral cavity reenter the root cavity.The above mentioned are in
      conformity with the Bernoulli's equation.

PMID- 15159933
TI  - [Immunohistochemical detection of PCNA and p53 protein in the premalignant
      lesions and squamous cell carcinomas of the oral mucosa]
AB  - PCNA and p53 protein expression were detected by immunohistochemical technique in
      39 oral premalignant and malignant lesion;which included 11 oral mucosal
      leukoplakia(LK),9 oral lichen planus (LP),7 in situ carcinomas(ISC) and 12
      squamous cell carcinomas(SCC);in order to investigate the significance of PCNA
      and p53 Protein overexpression in predicting malignant transformation.The results
      showed that the gradual strong expression of PCNA and mutated p53 protein
      positive signal from premalignant to malignant lesions.The remarkable correlation
      were found on PCNA expression between LK and ISC; on p53 protein expression
      between SCC I grade and SCC II grade and on PCNA and p53 protein expression
      between premalignant and malignant lesions.The results imply that expression of
      PCNA and mutated p53 protein may be as indicators for potential malignant
      development in benign lesions of oral mucosa premalignant.

PMID- 15159934
TI  - [The observation of the contained fluoride sealant on caries prevention for 3
      years]
AB  - Pit and fissure sealant is an effective method for preventing pit and fissure
      caries,though it has less effect in smooth surface teeth.But the contained
      sealant is effective on caries prevention both in pit and fissure area and in
      smooth surface.The aim of the present search was observing the clinic results of
      the contained fluoride sealant on caries prevention.786 children aged 6-8 years
      old were divided into four groups.The first permanent molars in group 1 were
      sealed by the contained fluoride sealant and those in group 2 were used the
      conventional sealant.The same molars in group 3 were used the conventional
      sealant plus the APFI gel and those in group 4 were only used the APFI gel.APFI
      gel was used one time per half year.The results showed the caries preventive
      effect of the contained fluoride sealant was significant higher than the
      conventional sealant or the APFI gel in first molars which had been sealed for
      three years.The caries incidence of the unsealed teeth in group 1 was lower than
      that in the other groups.The results also indicated the caries preventive effect
      of all above methods was less in female than in male.

PMID- 15159935
TI  - [Clinical study of benign cementoblastoma: A report of 32 cases]
AB  - This paper reported 32 cases of benign cementoblastoma and studied both clinical
      and radiographic features and also discussed their treatment.It was found that
      cementoblastoma was occurred more often than it was being described at past.The
      main site of tumor involvement is retromolar area of the jaw with common symptom
      of pain and swelling.In sciagram,the mass was more linked with teeth roots and
      periodontium,there is compact radiolucency in peripheral part.The tumor's image
      was seen often as a single,lower radiolucency area.We suggest a regime of
      curettage and tooth extraction to get a good therapeutic result.

PMID- 15159936
TI  - [Clinical evaluation of ceramic inlay made by CAD/CAM for 3 year]
AB  - In this study,ceramic inlays made by CAD/CAM system were used to restore
      posterior tooth defects.After three years of clinical observation on 21
      prostheses no secondary caries was found and patients satisfied with their
      restoration on aspects of color match and resistance to wear etc.Five cases of
      inlay fracture and of obvious space between inlay margin and Cavowall were
      found.The main reason was the insufficient thickness of the inlays meanwhile the
      selection of bonding agent was not appropriate.The clinical successful rate is
      76.20%.As CAD/CAM is a sophisticated technique induced into prosthodontic area
      just in 1980's,it has still some deficiency to be improved and perfected.

PMID- 15159937
TI  - [Detection of the causes of clinical failure of bioactive glass titanium alloy
      core implant]
AB  - Total number of 252 implants made of titanium alloy coated with a suitable
      bioactive glass were applied in clinic from October,1988 to July,1994.The success
      rate is 90,47%,24 implants failed with failed rate of 9.53%,The authors have also
      discussed the cruxes of success,causes of clinical failed,implantitis and
      complication of prosthesis,and given the new conception of re-implanting.

PMID- 15159938
TI  - [Cephalometric analysis in the patients of TMJ ankylosis with OSAS: Skeletal
      morphology]
AB  - By cephalometric analysis of 18 normal men and 12 men who got TMJ ankylosis with
      obstructive sleep apnea syndrome(OSAS),the authors reported that there were
      cephalometric characteristics in the patients:the craniomaxillofacial bones
      displacement posteriorly and superiorly,and demonstrated that it is key to
      advance the patients' jaws and enlarge the upper airway space.

PMID- 15159939
TI  - [Cephalometric analysis in the patients of TMJ ankylosis with OSAS: Soft tissue
      morphology]
AB  - By cephalometric analysis of 18 normal men and 12 men who got TMJ ankylosis with
      obstructive sleep apnea syndrome(OSAS),the authors reported that there were
      cephalometric characteristics in the patients:the posterior airway space(PAS)
      decreased(P<0.001),and the rate of (TA+SPA)/OPA remarkably increased(P<0.001),so
      the two parameters are significant for the diagnosis and treatment of the
      patients.

PMID- 15159940
TI  - [The pre-and-postoperative cephalometric evaluation on the patients of TMJ
      ankylosis with OSAS]
AB  - After taken the comparative studies on the cephalometric analysis of the patients
      of TMJ ankyolsis with OSAS pre-and-post operation,the authors demonstrated the
      method combining TMJ reconstruction and orthognathic surgery is responsible to
      the patients.

PMID- 15159941
TI  - [Use of B type color ultrasonography in oral and maxillofacial surgery]

PMID- 15159942
TI  - [Restoration of 278 difficult cases with complete denture]

PMID- 15159943
TI  - [Harvest of the free radial forearm flap: Experience in 36 cases]

PMID- 15159944
TI  - [The use of ulnar forearm flap: Clinical evaluation]

PMID- 15159946
TI  - [Restoration of 117 subgingivally fractured teeth with crown]

PMID- 15159945
TI  - [Treatment of oral diseases with pulsed Nd:YAG laser: Experience in 174 cases]

PMID- 15159947
TI  - [Treatment of osteomyelitis of the jaw with hyperbaric oxgen]

PMID- 15159948
TI  - [The use of rigid internal fixation in treatment of fractures of the jaw bone]

PMID- 15159949
TI  - [Restoration of wedge-shaped defects with light cured composite resin: Causes of
      treatment failure]

PMID- 15159950
TI  - [The use of biodegradable polymeride in the field of dentistry]

PMID- 15159952
TI  - [Vital pulpectomy in 300 deciduous teeth with FC: Clinical analysis]

PMID- 15159953
TI  - [Treatment of arsenic apicitis with dexamethasone and iodine: Clinical
      experience]

PMID- 15159951
TI  - [Reconstruction of mandibular defects with free fibular flap: Review of the
      literature]

PMID- 15159954
TI  - [Clinical analysis of the treatment of 216 cases of dento-pulpitid patients]
AB  - Evaluating of 216 first time patients in our department,we divided two groups of
      complained teeth and non complained teeth,analyzed the location of numbers of
      focus,and the clinical data.The results showed the most important key procedure
      was to do best of full teeth examination and systematic treatment.

PMID- 15159955
TI  - [The primary study of articulation effect on the adults with cleft palate
      undergoing palatopharyngoplasty]
AB  - A retrospective study was performed in 15 adults with cleft palate who operated
      with palato-pharyngoplasty.Using frequency spectrum analyser to describe their
      Chinese vowel frequency spectrum curve character.Their articulation effect after
      sugery was analyzed.The result shows:The excellent rate of the articulation on
      effect appears 46.67%.The author believes that:the palato-pharyngoplasty can be
      utilized as a manner to cure the adults with cleft palate and the advanced effect
      is needed to be continuously studied.

PMID- 15159956
TI  - [Evaluation of 28 cases of salivary malignancies with MR imaging]
AB  - Twenty-eight cases of MRI of the salivary malignancies confirmed
      histopathologically were shown in this paper.By observing separately and
      comparatively with SE (spin echo) T2 weighted imaging and PE(field echo)
      imaging,the authors consider that (1)the malignant tumors within the salivary
      glands displaying low and intermediate signal intensities on T2 weighted image
      may be thought as a characteristic sign in the diagnostic processes. (2) PE
      imaging as an effective method is able to differentiate the tumors from the
      calcification and fibrosis which were low and intermediate signal intensities on
      T2 weighted image. (3)the locations and sizes of the tumors have directly
      influenced on their marginal manifestations and adjacent normal tissue
      structures.

PMID- 15159957
TI  - [Stress research on support tissues of Buffer-typed conical telescopic removable
      denture]
AB  - In order to explore the biomechanical physiology of Buffer-typed conical
      telescopic removable denture restoring defected dentition with a preponderance of
      teeth lost and only a few remained,the authors have studied the stress
      distribution of the periodontal support tissue of abutments and subbasal support
      tissue when subjected to forced transfered from removable denture of both Buffer
      typed and non Buffer-typed telescopic retainers.The results suggest that occlusal
      forces can be redistribute through dentures with buffer typed conical telescopic
      retainers which decrease forces sustained by abutments and increase the ones by
      subbasal support tissues thus avoiding trauma of abutments while having certain
      degree if physiological stimuli.We can also decrease the forces transfered to
      subbasal support tissues by expanding basal areas,so to alleviate the absorption
      of alveolar ridges.This resut is in accordance with clinical effects.

PMID- 15159958
TI  - [Three dimensional finite element analysis of margin configurations and stresses
      of porcelain fused to metal crowns]
AB  - As to using the method of three dimensional finite element,this study has
      analyzed the stress distribution of the porcelain fused to metal crowns with
      three different labial margin configurations under the forces from diverse
      direction.The results showed that the chamber margins exhibited fewer tensile
      stresses than the shoulder or shoulder with a bevel margins.The labial margin
      exhibited more tensil stresses when the incisal edge of the crown was loaded with
      labial forces.so,we provide the mechanical basis for the conclusions as follows:
      (1)The labial chamber margin is preferable to shoulder or shoulder with a bevel
      margin. (2)The porcelain may fracture when the incisal edge of porcelain fused to
      metal crown is loaded with labial forces.

PMID- 15159959
TI  - [Study on the compatibility of slip casting aluminous ceramic crowns]
AB  - One of the key factors for a good slip casting aluminous ceramic crown is good
      compatibility between its core material and the veneering porcelain.The chemical
      and thermal compatibility of two slip casting aluminous ceramic crown systems(In
      Ceram and GI-I) were investigated by means of SEM and EDAX,thermal shock tests
      were also performed to evaluate the crazing resistance.The results showed: the
      crazing resistance of In-Ceram was 158 degrees centigrade,and that of GI-I was
      degrees centigrade;there existed tightly bonded interfaces between the slip
      casting aluminous ceramic cores and the veneering porcelains in both of the two
      systems,where ion transferences were found.The results also suggested good
      compatibility of the two slip casting aluminous ceramic crown systems.

PMID- 15159960
TI  - [Three dimensional FEM analysis of stress distribution around dental implants to
      estimate the influence of the length]
AB  - The effect of the length of implants on stress distribution is one of the
      important subjects in implantology.In this study,Three dimensional finite element
      methods model was constructed by dental CT images,The purpose of this study was
      to evaluate the stress distribution in bone adjacent to an implant after
      application of loading in horizontal,oblique and vertical direction.It was show
      that the highest stress occured at the cervical bone margin adjacent to the
      implant only 10% decrease in inverse two times increase in implant length,and
      correlated little to the implant length,therefore,it was unnecessary to emphasize
      the length of the implants in clinic.

PMID- 15159961
TI  - [The influences of lanthanum,cerium and fluorine ions to the activity of
      collagenase degrading cemental collagens]
AB  - The influences of trace elements lanthanum,cerium and fluorine to the activity of
      clostridium histolyticum collagenase(CHC) during the period of CHC degrading the
      cemental root collagen in vitro is studied.The results reveal that La(3+) can
      significantly inhibit the activity of the CHC than Ce(3+) and F(-). Therefore it
      suggests that lanthanum may be used as a new kind of element in preventing root
      caries.The mechanisms of above functions are also discussed.

PMID- 15159962
TI  - [The study of cellular dynamic varied features on golden hamster cheek pouch
      premalignant model]
AB  - Researching the model of golden hamster cheek pouch premalignancy not only had
      significance on treating and preventing oral epithelial cancers,but also could
      furnish the reference material about other similar hidden tumors.In this
      study,immunohistochemistry ways(proliferation cell nuclear antigen
      PCNA,bromodeoxyurdine-BRDU) combined with light and electric microscopic
      observation were applied to study cellular dynamic varied features on golden
      hamster cheek pouch premalignant model induced by dimethylbenzanthracence
      (DMBA).The results showed that both S-period cells and DAN's synthesis increased
      in the development of premalignancy,then,discovered the basis of cellular
      dynamics of the model.

PMID- 15159963
TI  - [Correlative analysis with proliferating cell nuclear
      antigen,bromodeoxyuridine,and microscopic observation on golden hamster
      carcinogenesis model]
AB  - The early diagnosis of carcinomatous conversion has special significance on
      increasing effectiveness.Proliferating cell nuclear
      antigen(PCNA),bromodeoxyuridine(BRDU)(immunohistochemistry ways),and microscopic
      diagnosis were applied and observed on golden hamster cheek pouch carcinogenisis
      model induced by dimethybenzanthracene(DMBA) in order to seek
      simple,effective,leading and reliable diagnostic way.The results showed that
      three observable means had significant correlation,and demonstrated that
      immunohistochemistry ways practical value in diagnosis of carcinomatous
      conversion.This study suggests that PCNA and BRDU are more sensitive,simple and
      reliable,and two hopeful methods of early diagnosis of carcinomatous conversion.

PMID- 15159964
TI  - [The light microscopic observing analysis of 12-item pathological features on
      golden hamster cheek pouch dysplasia]
AB  - Grading objectively serious degree of oral mucosal premalignancy has instructive
      significance to its outlook and effectiveness.In order to supply experimental
      foundation of diagnosis epithelial dysplasis accruately,the sample of golden
      hamster premalignancy induced by dimethyblenzanthracence(DMBA) were made and
      observed microscopically.The results were recorded one by one according to 12
      item criteria of WHO.The results showed that 12-item criteria could summarized
      wholly the histopathological varied features in the every stage of epithelial
      dysplasia The frequency of occurrence of 12-itemcriterias suggests that the
      starting site of premalignancy be at the basal layer.Abnormal karyokinetic and
      mitogenic figures have special significance in the epithelial dysplasia of
      grading diagnosis and judging outlook.

PMID- 15159965
TI  - [Root canal therapy and RF-109 resinifying: Comparison of clinical results]

PMID- 15159966
TI  - [Simultaneous surgical management of ankylosis of the temporomandibular joint and
      mental deformity]

PMID- 15159967
TI  - [Treatment of recurrent aphtha ulcer with sheets containing radices salviae
      miltiorrhizae and varidase: Clinical evaluation]

PMID- 15159968
TI  - [Treatment of herpes stomatitis with Isatic indigotica Fort]

PMID- 15159969
TI  - [Dental filling material: Gallium alloy]

PMID- 15159970
TI  - [Burning mouth syndrome]

PMID- 15159972
TI  - [Treatment of 37 cracked posterior teeth: Clinical observation]

PMID- 15159971
TI  - [TWEED technique in orthodontics: Part II]

PMID- 15159973
TI  - [Analysis of malocclusion in patients with cleft lip and palate postoperatively]

PMID- 15159974
TI  - [Treatment of herpes simplex of the lip using hydropathic compress of virazole]

PMID- 15159975
TI  - [Caries survey in 2964 frontier defense soldier]

PMID- 15159976
TI  - [Self made tooth separating spring]

PMID- 15159977
TI  - [pilomatricomas of the preauricular area: Report of one case]

PMID- 15159978
TI  - [Familial congenital symmetrical loss of the upper and lower permanent teeth:
      Report of 3 cases]

PMID- 15159979
TI  - [Surgical approach plus Nd:YAG laser irradiation for the management of hemangioma
      in deep maxillofacial region]
AB  - This article introduces a new method for the management of cavernous hemangioma
      in deep maxillofacial region.Common surgical approach was carried out to expose
      the mass of hemangioma,then Nd:YAG laser was irradiated it without tumor
      removal.Immediatelly shrinking of hemangioma can be seen in all these seven
      cases.The therapeutic effect was satisfied in 3-12 months follow up.With the
      basic research of the rabbit facial nerve's Nd:YAG laser injured detecting
      experiment.We discussed its indication,advantage and interaction between laser
      and peripheral tissue.Our result shown that this new way is a good method for
      hemangioma in deep maxillofacial region as its advantages of skin preventing and
      peripheral normal tissue preserving

PMID- 15159981
TI  - [The influence of masking agent on adhesion of composite resin]
AB  - In this study we used light cured resin,opaque resin and composite resin/masking
      agent to bond 24 teeth in vitro and then we tested their bonding stress.We also
      used these three materials to treat 240 tetracycline stained teeth in
      clinic.After half a year,one year,two years follow-up we found:in vitro study,the
      highest stress of composite resin is 144.3kG/cm(2).There is no significant
      difference in statistics among these three materials if we used the masking agent
      or opaque resin or not.In clinical follow-up,there is no significant difference
      in shed,partial shed,margin stain,gingival inflammation,and unsatisfied rate in
      three groups.The author believed the masking agent or opaque resin has no
      influence on the stress of resin restoration.So when we treated tetracycline
      stained teeth,we could choose it to increase aesthetic feeling.

PMID- 15159980
TI  - [The clinical analysis of oral squamous cell carcinoma under age of 40 years old]
AB  - 44 cases of oral squamous cell carcinoma under 40 years old were analyzed
      retrospectively.The ratio of male to female was 1.93:1,the youngest was 3,and the
      majority were within 30-40 years old.The predict site was on the tongue,21 cases
      shown and accounting for 66.90%.Histologically,the most cases were highly
      differentiated,accounting for 81092%.About one half cases were present in the
      terminal clinical stage,and for tongue cancer,terminal stage cases were as high
      as 61.90%.The patients did not cooperate with treatment very well,only minority
      could fulfill combined therapy in strict meaning.The recurrence was high and
      might affected the prognosis.The results were discussed and literatures were
      reviewed.

PMID- 15159982
TI  - [McNamara cephalometric analysis for Shanghai adolescents and adults]
AB  - This paper collects 101 Shanghai adolescents and adults with normal occlusion and
      balance facial profile.Using McNamara cephalometric analysis,it develops linear
      cephalometric standards for Shanghai adolescents and adults.By mean of SAS
      statistic software package,the characteristics of craniofacial linear parameters
      were observed.

PMID- 15159983
TI  - [1354 freshmen's dental investigation]
AB  - 1354 freshmen have been investigated to discover the relationship between dental
      diseases and environments,living habits and personal sanitary conditions,because
      urban young men like sweet foods and snacks,the incidence of caries is greater in
      the cities than in the country,more people with tetracycline discolored tooth
      live in urban areas than in the rustic ones,which is due to dense living
      conditions, vulnerable to respiratory organs disease,medical conditions and
      convenience of taking tetracycline when ill;on the other hand,gingivitis is more
      common within the country students than within the city students,for those
      students from the country are used to brush their tooth after adolescence and
      usually have more dental calculus which is harmful to the gingiva.More than half
      of the investigated freshmen are ignorant of correct method of brushing and oral
      health and that is important factors of high rate of dental disease,according to
      the above reasons,the effective measures should educated to prevent dental
      disease.

PMID- 15159984
TI  - [The clinical research of the tooth acid erosion disease in workers related to
      acid jobs]
AB  - Through investigation into 1671 workers who do six acid related jobs in fourteen
      factories,and 501 workers who work in non-acid condition in contrast.The paper
      has worked out the criteria of diagnosing occupational acid erosion
      disease,including the classified criteria of diagnosing single tooth acid erosion
      disease and the criteria of diagnosing different degrees of the tooth acid
      erosion disease in the oral cavity.It has also been found out that these are
      close relationships between the rate of suffering the occupational tooth acid
      erosion disease and the degree of the erosion,on the one hand and density of acid
      fog in the air and the types of acid workers are exposed ton and the length of
      the years working in such environment.

PMID- 15159985
TI  - [The effects of LTA and plaque on the periodontal tissue of the Guinea pig]
AB  - 40 Guinea pigs were divided into 4 groups.The gingival sulcus of 2 mandibular
      incisors were irrigated with LPS(Lipopolysaccharide),LTA
      (Lipoteichoicacid),PL(Subgingival plaque) and NS(Normal saline solution)
      respectively.2 animals were sacrificed in group of 5 successively at 1,2,3,6,8
      week after irrigation.Microscopic examination demonstrated:Only a few penetration
      of inflammatory cells lay in the gingival tissue in NS control group.Significant
      infiltrate associated with evident crystal resorption were noted at 1st week and
      active remodeling took place at 4th,5th week in LPS group.Enhancing accumulations
      of plaque calculus with weak inflammation could be seen in LTA group.Not only
      accumulations of plaque and calculus but also penetration of inflammation with
      resorption of bone were seen in PL group.Their effects on the periodontal tissue
      of Guinea pig showed evident different.These findings served further expression
      the possible mechanisms of periodontal diseases.

PMID- 15159986
TI  - [A study on change of proliferating cell nuclear (PCNA) during DMBA induce golden
      hamster cheek pouch carcinoma]
AB  - 109 cases were studied by immunohistochemisty with anti-PCNA antibody specimens
      which dyed by PCNA immunohistochemistry were counted with net and morphology
      observed.The results indicated that:a few of PCNA-positive cells had been seen in
      the basal cells of normal epithelium. An increased percentage of PCNA-positive
      cells was found in dysplasia and carcinoma.The increase between every grade is of
      statistical significance(P<0.05).In slight dysplasia grade group,the percentage
      od PCNA-positive cells increasing between applying DMBA-six-weeks' group is of
      statistical significance(P<0.05),and hadn't found statistical difference among
      the other groups.It is demonstrated that PCMA is one of criteria which were
      observed cell reproduction reactivities during precarcinoma,and it is more
      sensitive than light microscopy.

PMID- 15159987
TI  - [A comparative analysis of biological properties of glucosylrtanterases secreted
      by Streptococcus sanguis and Streptococcus mutans]
AB  - Our study make a comparative analysis of biological properties of
      glucosyltranterases(GTF) secreted by S.sanguis 34 and S.mutans Ingbritt(c).The
      results as follows:(1)S.sanguis 34 has more extractions of extracelluar GTF than
      S.mutans Ingbritt(c) under equal cultured conditions,but S.mutans Inggbritt(c)
      has more activity of extracelluar GTF than S.sanguis.These differences are
      identical with the difference of their cariogenicities;(2)GTF of S.sanguis 34 can
      also synthesize water-soluble glucan,and is a multienzyme complex system as
      S.mutans. S.sanguis might catalyse sufficient dextran formation to stimulate the
      primer-dependent activity of the S.mutans GTF enzyme. This might aid the adhesion
      of this comparatively late colonizer;(3)easier to obstruct high pure GTF of
      S.sangusi 34 S.mutans.

PMID- 15159988
TI  - [Environmental factors in oral cavity effect on growing of Streptococcus sanguis
      and Streptococcus mutans-effect of Mucin]
AB  - Our study use continues culture technique through adding mucin as the limiting
      element in chemically defined culture,medium in order to observe growing states
      of S.sanguis 34 and,S.mutants Ingbritt(c).The results as follows:S.sanguis 34
      were able to grow as pure culture on mucin;S.mutans was unable to grow as a pure
      culture on mucin,but attained a significant population size in the presence of
      S.sanguis.These results indicate a synergetic degradation of mucin by S.sanguis
      and S.mutans in mixed chemism culture.

PMID- 15159989
TI  - [Environmental factors in oral cavity effect on growing of Streptococcus sanguis
      and Strepococcus mutans-Oxygen of effects]
AB  - Oral Streptococcus species belong to facultative aerobes,and are easily inhibited
      by metabolic products of oxygen.Our study uses continues culture technique
      through adding oxygen in order to observe growing states of S.sanguis 34 and
      S.mutans Ingbritt(c) The result is that the resistance to oxygen of S.sanguis 34
      is stronger than S.mutans Ingbritt(c).This result is in accordance with the
      phenomenon that S.sanguis is a pioneer colonizing germ of dental plaque.The lower
      resistance to oxygen of S.mutans indicates that the growth and cariogenic action
      of S.mutans are dependent on the internal circumstance of plaque.

PMID- 15159990
TI  - [Modified method for repair of bilateral cleft lip]

PMID- 15159991
TI  - [Reconstruction of mandibular defects with revascularized iliac bone graft and
      monitoring of blood supply postoperatively]

PMID- 15159992
TI  - [Evaluation of the quality of life in patients with head and neck cancers:
      Literature review]

PMID- 15159993
TI  - [Taking the retruded contact position of the mandible using blade induction
      technique]

PMID- 15159994
TI  - [Detection of the distribution of PGE(2),6-K-PGF(1alpha) and TXB(2) in the
      periodontal ligament cells with immunohistochemical staining]

PMID- 15159996
TI  - [Odontogenic Pinborg tumor(extraosseous type): Case report]

PMID- 15159995
TI  - [Treatment of extraoral type cyst of the sublingual gland: Report of 17 cases]

PMID- 15159997
TI  - [Training of dental students for health education potency: Evaluation of the
      teaching program]

PMID- 15159998
TI  - [Osteomyelitis of the mandible and anemia secondary to Albers-Schonberg disease:
      Case report]

PMID- 15159999
TI  - [Recurrent fetal cellular rhabdomyoma:histopathological and ultrastructural
      observations]
AB  - A mass of the neck in an 8-year-old boy diagnosed with recurrent fetal cellular
      rhabdomyoma was reported.The recurrent tumor consisted of undifferentiated round
      and short spindle cells and immature striated muscle cells,which was similar to
      the primary tumor occured in five years ago.However,there were more large round
      myoblasts which mainly located at the periphery of the tumor and osteoid stroma
      in the recurrent case immuno-histochemistry stain and ultrstructure observation
      suggested that these were undifferntiated mesenchymal cell and myoblasts.The
      differential diagnosis from fibrosarcoma,highly differentiated
      rhabdomyosarcoma,and hemangiopericytoma were dicussed.Author considered FRMs has
      a recurrent and malignant change tendency though it belongs to benign tumor.

PMID- 15160000
TI  - [The management of the treatment and diagnosis for the calcifying odontogenic
      cyst]
AB  - 18 Patients with calcifying odontogenic cyst underwent surgery in our Department
      from 1977 to 1993 were reported.8 male and 10 female aged from 11 to 52 with
      medium or 33 years were included.16 cases were pathologically confirmed as
      primary intraosseous cyst(central),and 2 as extraosseous cyst(peripheral).There
      was no recurrence after the local excision for preripheral calcifying odontogenic
      cyst and local curettage for central one.There were 3 in 6 cases of tumor typed
      cyst who had recurred postoperatively,two of them had recurred repeatedly and
      cured by means of local radiotherapy.The authors recommend that the tumor type of
      intraosseous calcifying odontogenic cyst be classified as a border-line tumor and
      treated as well as the principles of low malignant tumor.Post-operative
      radiotherapy could be used for recurrent cases.

PMID- 15160001
TI  - [Analysis of the clinic with pathology and detection using IGSS of 201 cases of
      discoid lupus erythematosus]
AB  - Clinic pathology and detection using IGSS of 201 cases of discoid lupus
      erythematosus (DLE) were studied in this paper.The results showed:1.DLE usually
      occured on the low lip(60%);2.Suffering from gastrointestinal disease were the
      first symptom(25%DLE cases was confirmed by mild dysplasia,3 cases of carcinoma.1
      cases Combined of DLE and lichen planus(LP);4.Immunogold-silver Staining (IGSS)
      was applied to detect immune complex.The result indicated that Fg,immunoglobins
      and complement C3 deposited at basal membrane zone of DLE.It is illustrated that
      DLE is an autoimmune disease which is caused by many kinds of factors and may be
      cancerous.Coexistence of DLE and LP suggested that they may be at different
      stages of the same disease.Its mechanism will be further studied.

PMID- 15160002
TI  - [A clinical observation on 218 maxillary first molars canal system]
AB  - 218 maxillary first molars were observed during clinical endodontic therapy for
      canal system;the number of canal,working length,and the location at the floor of
      each orifice.As to the patients;97 are male,121 are female,age from 13 to
      76.Results shown that each mesiobuccal root of 28 molars(12.84%) included two
      canals,there was no significant difference in canal number in the mesiobuccal
      root of maxillary first molar were decreased with the age.The suggestion was made
      the notice for the complicated canal system,improving the shape of access,holding
      the method to find out the second canal in the mesiobuccal root could avoid
      missing canal on treating maxillary first molars endodontically. The resinifying
      therapy seems to raise successful rate for treating molar with complicated canal
      system.

PMID- 15160003
TI  - [Fibrous dysplasia and malignant transformation of the maxillofacial region:
      Analysis of 18 cases]

PMID- 15160004
TI  - [Teatment of oral lichen planus with chloroquine and triamcinolone-A]
AB  - In this study,single blind grouping method was applied to compare the effect of
      chloroquine and triamcinolone-A which were used to treat 360 cases of oral lichen
      planus.The results showed the effect of local injecting triamcinolone-A was
      better than that of taking chloroquine,and also was better than that of taking
      triamcinolone-A accompained of chloroquine.Therefore,they were two effective ways
      to cure OLP and worthy of wide use.

PMID- 15160005
TI  - [A preliminary study on the relationship between Streptococcus and
      Neisseria,Veillonella in an artificial mouth model]
AB  - The viable cell count of monobacterial plaque of Streptococcus and mixed
      bacterial plaque of streptococcus and Neisseria Veillonella,also the
      demineralization caused by the plaques were observed.The assumption that
      Neisseria and Veillonella might reduce demineralization of enamel caused by
      streptococcus was confirmed.The relationship between streptococcus and
      Neisseria,Veillonella were preliminarily found out.

PMID- 15160006
TI  - [Effects of shade of visible light cured composites on their polymerization]
AB  - Conversion degree of double bonds,microhardness and cure depth of different shade
      of two visible light cured composites were inspected by means of the Fourier
      transform infrared spectroscopy and other techniques.The results showed that
      polymerization in the deep of visible light cured composites was significantly
      affected by shade of resins.The cure uniformity and the cure depth of darker
      resins were lower than those of lighter ones.

PMID- 15160007
TI  - [Diagnostic arthroscopy of the Maraca mulatto's TMJ]
AB  - To gain further knowledge about features of Maraca mulatto's TMJ,occlusion,and
      teeth,we underwent examining 4 rhesus monkeys with 8 joints.The same and
      different features were concluded between Maraca mulatto's anatomical structures
      and human begins.Afterwards,10 aged rhesus monkeys with 20 joints were examined
      by TMJ arthroscopy.The results showed that the appearances in 70%(14/20) of the
      aged were the same as those in human pathologic TMJs. In conclusion,the Maraca
      mulatto can suffer from the same arthropathy as human being,and it is possible to
      choose the aged as a natural pathologic model.

PMID- 15160008
TI  - [A prospective study evaluating effectiveness of TMJ arthroscopy for particular
      stages of internal derangement]
AB  - The purpose of this prospective study is to evaluate effect on particular stages
      of internal derangement by TMJ arthroscopy.According to Wilkes-Bronstein
      classification,the distributions between 81 joints and particular stages of ID
      were:25 joints in II stage,18 in III,24 in IV,and 14 in V.The total 81 joints
      were undergone by arthroscopic surgery,the total success rates of different
      stages of ID were:24/25 joints in II stage,16/18 in III,13/24 in IV,and 7/14 in V
      particularly.The success rates were no statically significance (P>0.05) between
      II stage and III stage or between IV and V or V stages.The conclusion is that
      these cases in II or III stages of ID choose arthroscopic surgery than those
      cases in IV or V stages.

PMID- 15160009
TI  - [A retrospective study evaluating effectiveness of different TMJ arthroscopic
      techniques for discal displacement with or without reducing]
AB  - The three arthroscopic techniques were particularly method I(lysis and
      lavage),method II(disc repositioning and sclerotherapy plus method I),method
      III(traction,fixation plus method II) in order to make comparative study.The
      distributions between the 76 joints and three techniques were:14 joints in method
      I,31 in II,and,31 in III.The total follow-up was 30m(6-84m),and the total success
      rate was 73.7%(53/76).The mean follow-ups were particularly:28.6m in method
      I,38.4m in II.and,74.2%(23/31) in III,particularly.There were no statically
      significance between I and II.In disc displacement with reducing,there were no
      statically significance between method II(18/20) or III(14/15) and I(1/40),and no
      statically significance between II and III.In disc displacement without
      reducing,there were no statically significance between method I(6/10)and II(8/11)
      or III(9/16),or between II and III.Conclusions were that II or method III was
      effective on disc displacement with reducing,and that it don't make clear for any
      one of three methods to be more effective on disc displacement without reducing.

PMID- 15160010
TI  - [Surgical approaches to tumors in the parapharyngeal and infratemporal space:
      Report of 18 cases]

PMID- 15160011
TI  - [Clinical analysis of 92 infants with necrotic cellulites of the floor of mouth]

PMID- 15160012
TI  - [Use of a versatile labial arch: Clinical experience]

PMID- 15160013
TI  - [Current status of diagnosis and treatment of mucosal melanoma of the head and
      neck]

PMID- 15160014
TI  - [Modifications of the traditional cephalometrics]

PMID- 15160015
TI  - [TWEED technique for orthodontics: Part I]

PMID- 15160016
TI  - [Detection of T cell subtypes in the epithelium of oral lichen planus lesions]

PMID- 15160017
TI  - [The removable partial ceramic denture with lingual wing plate without clasp]

PMID- 15160018
TI  - [restoration of residual crown and root with light cured complex/polycarbonate
      crown and threaded root canal dowel pins]

PMID- 15160019
TI  - [Pulmonary metastasis from the malignant neoplasms of major salivary gland:
      Clinical analysis of 22 patients]

PMID- 15160021
TI  - [Oral health survey in 2023 workers and staffs]

PMID- 15160020
TI  - [Repair of cleft palate in 16 infants: Clinical outcomes]

PMID- 15160022
TI  - [Quantitative study of velopharyngeal function post-palatoplasty]
AB  - The computer of nasopharyngeal fiberscope(NPF) for quantitative analysis was
      carried out to assess the palate articulation of 43 subjects,and normal
      articulation of 60 subjects.The rest,/a/,/s/and /m/ articulation of NPF pictures
      were calculated for veloparyngreal function via computer.

PMID- 15160023
TI  - [Clinical management of tumours in the infratemporal fossa and parapharyngeal
      space:A report of 44 cases]
AB  - From June 1971 to June 1993,44 cases suffered from tumors of the infratemporal
      fossa and parapharyngeal space were summarized on their materials showing thirty
      one of them were benign tumors which first arised in the true deep lobe of the
      parotid gland and next in the neruolemma.Thirteen cases were malignant tumors
      arising in several tissues.The chief clinical sign in these patients was a
      lateral pharyngeal wall bulge and deformity without pain.A few patients occured
      change in voice characteristics or diffculty in swallowing.All these patients
      were performed surgery.93%(41/44)of patients were followed up.The longest follow
      up has lasted 20 years.In this paper,the specific clinical appearance,diagnosis
      and surgical technique for tumors of the infratemporal fossa and parapharyngeal
      space are further discussed by us.

PMID- 15160025
TI  - [Atypical fistula caused by periapititis: Case report]

PMID- 15160024
TI  - [A quantitative study on mandibular incisor point border movement between the
      immediate complete denture wearers and the second complete denture wearers]
AB  - The mandibular incisor point border movement orbits of 20 patients wearing
      immediate complete dentures for 3 months and the same patients wearing the second
      complete dentures for 3 months were raced by SGG then measured and analysed.The
      results showed that the ranges of mandibular incisor point border movement of
      patients wearing immediate complete dentures for 3 months were significantly
      narrower than those of the same patients wearing the second complete dentures for
      3 months (P<0.01).The ratio of the former to the latter was only 59.00%-69.96%.It
      could be concluded that the ranges of mandibular incisor point border movement of
      immediate complete denture wearers were limited.Thus the immediate complete
      dentures were transitional dentures and only used for treating purpose.The
      patients must have another pair of complete dentures after 3 months interim.

PMID- 15160026
TI  - [Clinical summary of relatively large dose of sodium morrhuate injection for the
      treatment of maxillofacial cavernous hemangionma:A report of 764 cases]
AB  - The result of relatively large dose of 5% sodium morrhuate injection(SIM) for the
      treatment of 764 cases in the cavernous hemangioma in orofacial region is
      presented.The curative rate was improved,Its cure and elementary cure rate were
      89.27%.The dosage,course and practical approach were discussed,The relationship
      of factors listed above with the curative effect were mentioned.The reaction and
      complications might be influencing the recurrence rate.Hemangioma after SMI
      should be observed in order to consolidate its curative effect.

PMID- 15160027
TI  - [Observation of the effectiveness of compound Gynostemma Pentaphyllum Mak in
      golden hamster cheek pouch's premalignancy]
AB  - Premalignant model was established successfully in this study.At the same time,we
      applied compound Gynostemma Pentaphyllum Mak to conduct experimental research to
      block development of oral mucosal premalignancy.The results showed from uniform
      to granular or verrucous leukoplakia,there was the stage in which Gynostemma
      Pentaphyllum Mak could block oral mucosal premalignancies.The group which was
      firstly given to Gynostemma Pentaphllum Mak then smeared was more advantageous
      than the one which firstly smeared then given to the same drug.The
      experimentation demonstrated that Gynostemma Pentaphyllum had the functions of
      preventing and resisting cancer.There will be applied prospect in preventing and
      treating oral mucosal premalignancy.We should make further research in the
      future.

PMID- 15160028
TI  - [Malignant pleomorphic adenoma of salivary glands:A clinicopathologic study of 83
      cases]
AB  - This paper presented the clinicopathologic features of 83 cases of malignant
      pleomorphic adenomas(MPA) of the salivary glands.The average age of the patients
      was 53 years old.The ratio from male to female was 1.24 to 1.Thirty nine tumors
      located in parotid glands,twenty in submandibular glands and seventeen in
      palate.Histopathologically,the malignant component of 76 tumors was identified as
      carcinoma and 7 tumours as carcinosarcoma both in various types.The statistic
      analysis showed the factors which influenced the prognosis(P>0.05) included 1.
      location,2. histologic subtype of malignant component,3.differentiation
      grade,4.infiltration status,and 5.with or without lymph node metastasis in the
      initial operation.The prognosis of MPA was more ominous than that of/the
      conventional types of carcinoma,with only 52.7% of year survival rate.The authors
      concluded that the pleomorphic adenoma was the pre-cancerous lesion of
      MPA.Therefore,it is necessary to resect the pleomorphic adenoma as early as
      possible in order to prevent the occurence of the MPA.

PMID- 15160029
TI  - [Treating the fine canals and obstructed canals with ultrasound in 70 cases]
AB  - The fine canals and obstructed canals were treated with ultrasound in 70
      cases.Canals were re-enlarged and filled in 61 cases,with a success rate of
      89%.No lateral perforation or tooth facture was due to excessive loss of the
      teeth structure.This method was proved to be more effective and safer than
      traditional method.

PMID- 15160030
TI  - [The comparison of the effect of three restoration materials for the cavity
      convenience preparation]
AB  - The cavity restoration effects of light curing composite,chemical curing
      composite,glass ionomer were observed,for six and twelve months.The results
      showed that microleakage increased as time goes on inevitably.The failed
      incidence of class III restoration by glass ionomer was higher.The fact suggested
      that different preparation selected different materials.

PMID- 15160032
TI  - [The effects of retention and adaptation of complete denture on masticatory
      efficiency]
AB  - There are many facts of effectiveness on complete denture.Retention and
      adaptation are very important to denture's function among them.This thesis used
      soft relining material for 22 complete denture's patients whose pain,non
      retention and etc.resulted in the decline of masticatory efficiency to be
      treated.Masticatory efficiency is measured and analysed by light absorption
      method after treatment.The result shows there is closed relationship between full
      denture's retention and adaptation and masticatory efficiency.After
      relining,patient's masticatory efficiency is greatly improved due to increasing
      retention and adaptation.the masticatory efficiency after/before treatment is
      average 209%.Among these patients,mandibular changes are larger than
      maxilla.Author considers that soft relining is a good material for poor condition
      of alveolus dentis,mucosa and for old fragile man.

PMID- 15160031
TI  - [Clinical significance of the abnormal radiographic manifestations of pulp
      cavity]
AB  - Six cases showing abnormal radiographic appearance of the pulp cavity are
      presented in this article.According to the etiology.they are approximately
      divided into four patterns as follows:The first one was caused by hereditary
      disease,represented by mainly opalescent dentin.In the early stage,enlargement of
      the pulp cavity is obvious in radiograph,but in the late stage extensive atresia
      is observed.The second one was caused by tooth dysplasia.Its common clinical
      features are the maxillary lateral incisor accompanied by a lingual gingival
      groove and the mandibular second molar a "c-shaped" root canal.In radiograms,the
      former looks like a second root canal,while the latter regular pictures as if a
      reamer has perforated the pulp floor.The third one was caused by root
      fracture,especially root vertical fracture.The root canal space can be seen
      widened.The abnormal images might be due to the change of X-ray projected
      angulation.It's important that a clinical doctor must know all these in order to
      make correct diagnosis and render proper treatment.

PMID- 15160033
TI  - [A study on the influence of zinc on the growth and metabolism of streptococcus
      in an artificial mouth model]
AB  - The influence of zinc on the growth and metabolism of Streptococcus was studied
      under controlled conditions in an artificial mouth model.the results confirmed
      the previous conclusion that zinc was capable of inhibiting the growth and
      metabolism of streptococcus both vivo and in vitro.At the same time,the
      feasibility of the imitative experiments in an artificial mouth model was proved.

PMID- 15160034
TI  - [Treatment of trigeminal neuralgia of the third branch by transecting the
      mandibular nerve at a higher position: Report of 8 cases]

PMID- 15160035
TI  - [Leukemia first presenting as gingival bleeding at the dental department: Report
      of 8cases]

PMID- 15160036
TI  - [The method of quantitative analysis for trace elements in the hard tissues of
      the teeth]

PMID- 15160037
TI  - [Recent advances in the study of the cariogenic potential of Streptococcus mutant
      and marginal]

PMID- 15160038
TI  - [Normal MRI features of oral and maxillofacial region and diagnosis of related
      diseases]

PMID- 15160040
TI  - [Restoration of residual root and crown of the first premolar]

PMID- 15160039
TI  - [Surgical treatment of cleft palate: Experience in 196 patients]

PMID- 15160041
TI  - [The T cell changes in elder patients with recurrent aphtha ulcer]

PMID- 15160043
TI  - [Removal of fractured root tips of the posterior teeth using modified root
      erector and dental probe]

PMID- 15160042
TI  - [Experience in management of a patient with maxillofacial explosion injury]

PMID- 15160044
TI  - [A randomized clinical trial for the evaluation of head and neck squamous cell
      carcinoma treating with traditional Chinese medicine]
AB  - This paper described the research design,research process and statistical
      analysis of randomized clinical trial by treatment with traditional Chinese
      medicine in patients with squamous cell carcinoma of the head and neck.At first
      we found there was no significant difference between treating group and contral
      group(P>0.05) using log-rank test on Kaplan-Meier survival curves. With further
      multivariate analysis Cox model and after adjusting for sex,age,legth of taking
      the assigned medication,grade of tumor differentiation and using of
      chemotherapy,the rate of tumor-related death for control group was significantly
      higher than that for treating group :hazards ratio estimate was 1.939(95%
      confidence interval 1.008-3.729,(P<0.05).The length of taking Chinese medicine
      was one of the most important prognostic factors(P<0.001).The results suggest
      that the prescribed medication contributed to the improved survival,and it was an
      independent prognostic factor.

PMID- 15160045
TI  - [The clinical analysis of malignant change in oral lichen planus]
AB  - In this study,633 cases of oral lichen planus,which were confirmed
      histologically,had been observed and followed-up for 1-17 years.The results show
      that 8 cases of them were malignant change with the incidence of 1.3% and sex
      ratio in 3 males and females.The mean age of malignant change group was 50.9
      years.The patient's mean history was 10.9 years.The sites involved in buccal
      mucosa,lower lip,and the border of ventral tongue mucosa.The type of the lesion
      was all ulcerative type except 1 case with proliferation.In the present group 7
      cases were followed-up for the mean time of 3.6 years,and 2 cases were found the
      recurrence of cancer.

PMID- 15160046
TI  - [Root canal filling on one visit after disinfection with microwave: Clinical
      outcomes]

PMID- 15160047
TI  - [Using microvascular decompression of nervous reduces to treat primary
      prosopalgian and prosopospasm]
AB  - Primary prosopalgian and prosopospasm are common clinical problems considered
      obstinate diseases without effective therapy in the past.Since June
      1990,microvascular decompression of nervous reduces in pontocerebellar corner by
      posterior pathway of sigmodeus sinus has been performed on 141 patients with
      porsopalgian 117 cases and prosopospasm 24 cases.All patients were cured with the
      operation only once,which were no recurrence followed up from 6 months to 4 years
      and 6 months.This report elaborates the method and precaution of the operation,it
      also discusses the causes.

PMID- 15160048
TI  - [Experiment study on biological and immunological characteristics of modified DNL
      of oral squamous cell carcinoma with TNF-alpha gene]
AB  - Growing characteristic of gene-transduced and nontransduced DNL in medium of
      containing rIL-2 was compared,and growing characteristic of gene-transduced DNL
      in medium of non containing rIL-2 was analyzed.DNA index (DI),cell cycle and
      immunologic phenotypes of gene-transduced and nontransduced DNL were analyzed
      with FACS.The results revealed interfered with growth,DL,cell cycle and
      immunologic phenotypes of DNL,and gene-transduced DNL couldn't growing
      infinitely.

PMID- 15160049
TI  - [Pulsed ND:YAG laser irradiation and 2% NaF treatment in caries-like lesion
      formation in enamel:an in vitro study]
AB  - The purpose of this in vitro study was to determine the combined effects of
      ND:YAG laser irradiation and 2% NaF on caries-like lesion formation in human
      enamel.There were four groups:(1)control;(2)Nd:YAG laser only;(3)2%NaF
      only;(4)Nd:YAG laser before 2% NaF.The result show the lesion body depths were
      significant differences between the control group and all treatment group,and
      between Nd:YAG laser before 2% NaF group and both Nd:YAG laser group and 2% NaF
      group(P<0.05).The surface zone depths between Nd:YAG laser before 2% NaF group
      and both 2% NaF group and both 2% NaF group and control group were also
      significantly different(P<0.05).

PMID- 15160050
TI  - [The antibacterial efficacy to obligate anaerobes isolated from the infected root
      canal of deciduous teeth]
AB  - TMJ osteoarthrosis(OA) is frequently seen in the Oral and Maxillofacial Surgery
      clinics.In order to investigate cellular and molecular basis of the pathogenesis
      of TMJOA,the levels of IL-1 and IL-6 in synovial aspirates from different stages
      of TMJOA patients were determined and analysed.It was found that both of them
      were highly correlated with the severity of TMJOA(P<0.0001).A positive linear
      correlation was also found between IL-1 and IL-6(P<0.0001).The balance and
      imbalance between MMPs and TIMPS and the modulatory mechanism of cytokines were
      introduced and their possible roles in the pathogenesis of TMJOA were discussed.

PMID- 15160051
TI  - [Influence of green tea polyphenols varnish on saliva]
AB  - This study observed the inhibitory effect of green tea polyphenols varnish on the
      activity of humman saliva.We found 0.78 and 1.56mg/ml green tea polyphenols
      varnish is the best.We also observed the release of green tea polyphenols from
      liquid varnish is more than that from membraniform vanish.The release quantities
      of green tea polyphenols from membraniform is limited,suggest the influence of
      green tea polyphenols varnish on the activity of human saliva is small.

PMID- 15160052
TI  - [Histopathological and ultrastructural studies of melanomatic neuroectodermal
      tumor of infancy]
AB  - Three cases of melanomatic neuroectodermal tumor of infancy(MNTI) were
      studied.The tumor mainly consisted of small neuroblastic-like cells and pigmented
      large cuboidal cell,and infiltrated adjacent tissues.The main ultrastructural
      charactristics were the presence of some membranebound dense-core secretory
      granules,numerous free ribosomes and polysomes aggregaed in rosettes,occasional
      mitoses in the small cells;and four types of membranebound pigment granules
      corresponding to melanosomes at different stages of maturation in the pigment
      cell.immunohistochemical results indicated that both of main cells were positive
      reaction for NSE,negative for S-100.These facts suggested they are immature in
      and malignancy.Further,the isogenesis of the tumor cells and embryo optic cup
      cells were discussed.

PMID- 15160053
TI  - [The establishment and analysis of expending dental arch]
AB  - Expending dental-arch is one of the methods being used popularly in
      orthodontics.but there are few researches on its basical laws.In this paper,we
      used mathematic methods to discuss the relationship of the arch-length(S),the
      width(A),and the length of dental-arch(H).We devised a mathematic model,hoping it
      could be useful to orthodontic therapy.

PMID- 15160054
TI  - [Clinical results of lower lip reconstruction]

PMID- 15160055
TI  - [Treatment of periapical diseases with empty root canal therapy: Analysis of
      causes of failure in 218 cases]

PMID- 15160056
TI  - [Substitution of the first molar with the second molar for fixed orthodontics:
      Results and evaluation]

PMID- 15160057
TI  - [Management of patients with mental diseases who underwent oral and maxillofacial
      surgery: Clinical experience]

PMID- 15160058
TI  - [Treatment of recurrent aphtha ulcer with rinse containing hydrocortisone and
      gentamycin: Clinical evaluation]

PMID- 15160059
TI  - [The role of X ray examination in detection of caries]

PMID- 15160060
TI  - [The tissue markers in epithelial areas of oral precancerous lesions]

PMID- 15160061
TI  - [The commonly used immunologic assays and their clinical significance in oral and
      maxillofacial diseases]

PMID- 15160062
TI  - [Restoration of wedge-shaped defects with SGC-II glass ionomer cements:
      Preliminary experience]

PMID- 15160063
TI  - [Inconspicuous foreign bodies in oral and maxillofacial region: Analysis of 12
      consecutive cases]

PMID- 15160064
TI  - [Root canal filling with gutta percha and iodine: Clinical aspects]

PMID- 15160065
TI  - [Clinical analysis of ankylosis of the temporomandibular joint]

PMID- 15160066
TI  - [Surgical treatment of thyroglossal tract cyst: Clinical analysis of 27
      consecutive patients]

PMID- 15160067
TI  - [Establishment and clinical application of Chinese language clear degree]
AB  - This study was established the Chinese language of clear degree.The subjects of
      this study consisted of 50 patients with postoperative of cleft lip and
      palate,congenital velopharyngeal incompetence,and 30 control group were normal
      articulation of persons.The results of this study may be helpful for further
      clinic of the cleft lip and palate patients of speech therapeutics.

PMID- 15160068
TI  - [A study of the relationship between electromyographic activity of the
      masticatory muscles and the variations of the occlusal vertical dimension for
      edentulous subjects]
AB  - The study was performed in fifteen edentulous subjects with the EMG activity were
      recorded at the varying occlusal vertical dimension maintaining constant bite
      force value of 4kg.The results showed that maintaining constant bite force the
      amplitudes of EMG activity of the anterior temporal and masseter muscles are
      decreased with increasing the occlusal vertical dimension and correlation
      relation between them,that there is a stable region about 1.0mm for the anterior
      temporal muscle and about 1.5mm for the masseter muscle during the changes in
      electrical activity.It is represent that there is a physiological region of the
      occlusal vertical dimension for edentulous patient.

PMID- 15160069
TI  - [The treatment of unilateral true ankylosis of TMJ with maxillomandibular
      deformities]
AB  - The authors described a surgical procedure for the treatment of unilateral true
      ankylosis of TMJ with maxillomandibular deformities.The surgery included
      arthroplasty and Le Fort I maxillary osteotomy in one or two stages.It
      successfully not only restore the stomatognathic function with a maximum mouth
      opening in normal range,but also corrected malpositioned maxilla and mandible
      normal anatomic position.Postoperative orthodontic anatomic
      position.Postoperative orthodontic treatment was also performed for the
      improvement of masticatory function.The indications of the surgical procedure,and
      intraoperative precautions are discussed.

PMID- 15160070
TI  - [The evaluation of panoramic sialography applied in the diagnosis of parotid
      tumas]
AB  - Panoramic sialography is a new method applied in the diagnosis of parotid
      tumors.we have examined 33 cases of parotid tumors by this way and: 1.In
      sialograms of benign tumors,we discovered obvious filling-deficiency areas and
      moving position of ducts as well as margins of mass. 2. We also found interrupted
      branches of duct and transudation of contrast medium in sialograms of malignant
      tumor,in addition, the region of tumor could be depicted. 3.Thus,panoramic
      sialography has its distinctive advantages in nature of parotid tumors according
      to variations of ducts and globs with parotid gland.

PMID- 15160071
TI  - [The prevention and treatment of oral cavity ulcer and infection of patients with
      oral cavity malignant cancer after chemotherapy]
AB  - 44 oral cavity malignant cancer patients who underwent operation and chemotherapy
      are taken as the Experiment Group,using a mixture liquid of Calcii Folinas and
      Gentamycin to rinse out the mouth.48 patients using single drug gargle as the
      Comparison Group,The comparison between the two gargles' effects on oral ulcer
      and infection shows that the incidence of oral ulcer in the Comparison
      Group(P<0.05),and there is a significant difference.The oral infection incidence
      is lower too (P>0.05).There is no statistical difference.The expeiment suggests
      that gargling with mixture liquid is superior to using single drug liquid.

PMID- 15160072
TI  - [A clinical analysis of intramuscular hemangioma in oral and maxillofacial
      regions: Report of 59 cases]
AB  - From 1978 to 1992,the clinical data of 59 patients with intramuscular hemangioma
      in oral and maxillofacial regions were reviewed and analysed.The average age and
      the duration were 23 years old and eight years respectively.All patients were
      treated surgically,53 cases (89.83%)were completely resected and those of other 6
      cases(10.1%) partially resected without any complications,Follow-up for 11 months
      to 12 years showed that 2 cases relapsed,and thus the cure rate was
      96.6%(57/59),The author affirmed the significance of surgical operation in
      treatment and put forward the view of classification of hemangioma the vascular
      deformities.

PMID- 15160073
TI  - [A study of errors of radiography in 10000 intraoral periapical radiographs]
AB  - A total of 10000 full-mouth radiographs (10000 periapical radiographs were
      evaluated for radiographic errors.The result showed that four major types of
      errors were found in this study,They are cone cutting(5.59%),incorrect vertical
      angulation(38.84%),incorrect horizontal angulation(37.16%),and incorrect film
      placement (14.16%).The incidence of radiographic technique errors was 0.096%.Most
      errors were caused by incorrect vertical angulation and incorrect horizontal
      angulation(76%).Most errors were found in the cuspid premolar regions(70.6%)

PMID- 15160074
TI  - [Clinical study on wedge-shape ditch restoration with several restorative
      materials]
AB  - There appeared difficulties in either cavity preparation of restoration retention
      when wedge-shaped ditch was restored.In order to choose an ideal material and
      method restored wedge-shaped ditch,we used three kinds of restorative materials
      (glass ionomer,light curing glass ionomer,light curing composite resin)and four
      restorative methods (glass ionomer,light curing glass ionomer,light curing
      composite resin,glass ionomer mixed with light curing composite resin).carried on
      clinical observation.According to the results of six months follow-up,four
      methods have no significant differences in abrasion,fracture,shedding and failing
      incidence(including of abrasion,fracture,and shedding) through statistical
      test(chi-square test).According to the results of one year follow-up,there were
      significant differences in abrasion and failing incidence,but fracture and
      shedding have no significant differences.Results showed that light curing
      composite resin was better than glass ionomer in wedge-shaped ditch restoration.

PMID- 15160075
TI  - [Treatment of Sjogren's syndrome with self made SS sirup]

PMID- 15160076
TI  - [Influence of fluoride varnish of different concentration on microhardness of
      enamel surface]
AB  - Varnish is a new type oral material which develops rapidly in recently years,It
      have had extensive study abroad.It is one of the topical application of
      fluoride,among them,fluoride-sodium varnish have more significant effect on
      prevention of dental caries.This study observed the changes of microhardness of
      cramels after applying fluorid-sodium varnish of different concentration to
      enamel surfaces.Enamels were randomly parted into three groups,A.B and C.Before
      fluoride application,the microhardness of enamels were detected,and no
      significant difference were found among three groups,After that,0.5%,1.5%,2.7%
      fluoride-sodium varnish were daubed respectively on the three groups enamel
      surfaces for 24h.The microhardness of enamels were detected again.The results
      showed all the microhardness of enamels have significant increase statistically
      after applying fluoride-sodium varnish of different concentration.But,for 0.5%
      fluorid-Sodium varnish,the increase of microhardness of enamels was only one half
      of the other two group,which suggested in some concentration range,the fluoride
      concentration increased one time,the microhardness of enamels increased about one
      time, but the increase of microhardness of enamels was not synchronized with the
      increase of fluoride concentration.The increase of microhardness of enamels is
      almost the same between the two high concentration fluoride-sodium varnish
      groups,and there in no significant difference statistically.That is when some
      fluoride concentration were reached,the microhardness of enamels won't increase
      any more.By the experiment,the writer suggests 1.5% fluorid-sodium varnish is the
      best on prevention of dental caries.

PMID- 15160077
TI  - [Effects on the growth and development of mandible with different treatment
      following condylar neck fracture in rat]
AB  - The condylar necks of young rats are fractured on this experiment.Fractures are
      treated with nonfixation and fixation,The growth and development of mandible can
      be interrupted in two groups,with a relatively small in condylar head,a
      relatively thick in condylar neck.A coronoid and a mandible length are relatively
      short.But the growth and development of mandible almost are completed,bilateral
      mandibles are almost symmetry except for ramus.The difference are not found in
      between two groups.The results of this study implied that young condylar neck
      fracture may be treated by conservation.

PMID- 15160078
TI  - [Effects of demineral-resistant of Lanthanum,Cerium and Fluoride on human root
      surface:A comparative study in vitro]
AB  - An in vitro acid-resistant and remineralized study on human root surface with
      500ppm lanthanum,Cerium and Fluoride accidulate buffer was carried out in a pH-cy
      cling system.The results of quantitative chemical and energy spectrometry
      analyses showed that all these three elements had the demineral-resistant
      effects,although fluoride showed a better effect,Furthermore,the mechanisms of
      lanthanum,Cerium and Fluoride on demineral-resistant were discussed from the
      viewpoint of crystal physicochemistry.

PMID- 15160079
TI  - [Analysing the contents of prostaglandins in gingival fibroblast and periodontal
      ligament cell by microspectrophotometer]
AB  - This investigation analyses the contents of prostaglandin E(2)(PGE(2)),6-keto
      prostaglandin F(1a)(6-k-PGF(1a)) and thromboxane B(2)(TXB(2)) in gingival
      fibroblast (GF) and periodontal ligament cell(PDLC) by microspectrophotometer.The
      results showed that the absorbance of PGE(2) in GF was 0.25+/-0.03,the absorbance
      of 6-k-PGF(1a) was 0.20+/-0.03,there were significant difference between PGE(2),6
      k-PGF(1a) and control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) and
      control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) in PDLC each were
      0.20+/-0.20,0.16+/-0.03 and 0.13+/-0.02.They were much bigger than control
      group(0.07+/-0.01),which indicated prostaglandins in GF and PDLC can affect
      guided tissue regeneration and gingivitis degree,and there were important
      relationship between PG(s) in GF,PDLC and periodontitis.

PMID- 15160080
TI  - [Lymphoepithelial lesion of the minor salivary gland: Report of 2cases]

PMID- 15160081
TI  - [Prevention of stress gastric ulcer using Omepragol after oral and maxillofacial
      tumor surgery]

PMID- 15160082
TI  - [The design of retiform rest in casting denture]

PMID- 15160083
TI  - [The use of heart pacemaker in surgical treatment of patients with oral cancer
      and sick sinus syndrome]

PMID- 15160084
TI  - [Treatment of food impaction]

PMID- 15160085
TI  - [Extraction of impacted mandibular third molar: Clinical analysis of 656 cases]

PMID- 15160087
TI  - [The use of transcutaneous implants in facial reconstruction]

PMID- 15160086
TI  - [Study of the polymer dental coating films]

PMID- 15160088
TI  - [The study of bone maturation during growth and development]

PMID- 15160089
TI  - [Upper respiratory tract obstruction leading to death after resection of the
      submandibular gland: A case report]

PMID- 15160091
TI  - [Hamartoma of the head and neck: Clinicopathological analysis of 12cases]

PMID- 15160090
TI  - [The use of CT in diagnosis of oral and maxillofacial lesions]

PMID- 15160092
TI  - [Clinical analysis of 642 patients with maxillofacial injuries]

PMID- 15160093
TI  - [Analysis of DNCB immunologic reaction in 348 patients with oral squamous cell
      carcinoma]

PMID- 15160094
TI  - [The diagnosis value of malignant tumors in the Oral and Maxillofacial region
      using healthy person's free radical of hair]
AB  - Electron spin Resonance(ESR) was used to determine the free radical of hair from
      324 cases.These cases included 185 healthy persons,33 benign tumor patients,84
      malignant cases and 22 oral mucosa disease cases.The determined results were
      controlled with pathologic diagnosis to analyse the accordance. The result showed
      the positive rates of above mentioned cases were 5.9%,6.1%,84.52%and 9.1%
      respectively.The significant differences were observed when comparing the results
      of malignant cases with healthy person and benign tumor cases with healthy person
      and benign tumor cases(P<0.01).The ESR saturation power points of some malignant
      cases rose to above border-line(>10.0mW) after treatment.These results indicated
      using ESR to diagnosis early malignant cases and follow treatment effect possess
      certain clinical value.

PMID- 15160095
TI  - [An anesthetic study of 120 cases of orolingual tumor operations]
AB  - The anesthetic techniques of 120 cases of orolingual tumor operations was
      studied.The ages of 66 male and 54 female patients ranged from 7 months-77
      years,averaging 48.5 years.All the cases included 34 benign tumors and 86
      malignant tumors.This article analyses and discussed the choice of anesthetic
      methods,methods of induction and intubation and the features of control during
      operation and postoperative recovery.

PMID- 15160096
TI  - [Restoration of occlusion with telescope crowns: General considerations]

PMID- 15160097
TI  - [Reconstruction of post-traumatic maxillofacial deformity: Analysis of 100 cases]
AB  - This paper collects 100 cases with post-traumatic maxillofacial deformity.The
      types of deformity may be involved by order to concave appearance restricted
      opening of jaw,disturbance of occlusion,mimetic paralysis,scar,etc.The author
      advocate the treatment must be paid attention both appearance and
      function.Recently,we have used the vascularized flap,coronary
      incision,orthognathic surgery and rigid internal fixation in these cases,and have
      gotten better result than past.This paper emphasizes that we should pay attention
      to emergency treatment to reduce the occur of post-traumatic deformity.

PMID- 15160098
TI  - [Preliminary clinical study of endodontic antiseptic in monotithic type
      chlorhexidine controlled release delivery system]
AB  - The purpose of clinical study was to assess the bacteriological status of the
      root canal after disinfection with the monotithic type chlorhexidine enrolled
      release delivery system (CCROS).In experiments the monotithic type CCRDS was
      found to be more effective than the reservoir type CCRDS.The root canals of 24
      teeth with apical periodontitis were completely instrumented and irrigated with
      sodium hypochloride.After the instrumentations,12 teeth were treated with the
      monotitihic type CCRDS,12 teeth were treated with formocresol.Bacterological
      samples from the root canals were taken after 5 days using an anaerobic
      technique.The results indicated that monotithic type CCRDS was more effective
      than formocresol in obtaining bacteria-free root canals(Chi-square test
      P<0.05).The advantages of an antiseptic with along lasting effect for the
      elimination of bacteria form the root canal and for the prevention of reinfection
      were emphasized.

PMID- 15160099
TI  - [Hand grip strength as a nutritional indicator of patients with oral and
      maxillofacial malignancies to predict post-operative complications]
AB  - The correlation between hand grip strength(HGS),arm muscle circumference(AMC) and
      creatinine-height index (CHI) were studied in 127 patients with oral and
      maxillofacial malignancies.Prediction of postoperative complications by using HGS
      was also attempted in the patients undergoing surgical treatment.The results
      showed:(1)HGS correlated well with AMC and CHI,indicating that HGS can be used as
      a nutritional parameter to reflect the skeletal muscle condition(depletion or
      repletion);(2)comparison of the operative patients whose HGS<85% of the standard
      value(Group I)with those HGS>/=85% of the standard value(Group II)demonstrated
      that Group I hand a much higher incidence of postoperative complication(48.4%)
      than that of Group II (18.5%)(X=9.30;P<0.005),which means that HGS can be served
      as a nutritional prognostic indicator to predict postoperative complications.

PMID- 15160100
TI  - [Anesthesia of patients with giant maxillofacial tumors: Report of 3 cases]

PMID- 15160101
TI  - [On the anchorage aspects in Begg's technique]

PMID- 15160102
TI  - [A study on growth and development of maxillofacial region with vector analysis]
AB  - In order to observe the maxillofacial growth and development quantitatively, the
      vector analysis was applied in this study to divide Y axis,which is advocated in
      Downs method,into horizontal section and vertical one,from which the ratio of the
      facial growth separately in anterior and inferior direction was obtained.75
      pieces of x ray films for various dental stages of Shanghaiese with normal
      occlusion were selected and their angle of Y axis together with their cotangents
      were measured. The results showed that the cotangent of those with mixed,early
      permanent and permanent dentition were separately 0.47,0.48 and 0.45 indication
      that there was a certain relationship between anterior direction and inferior one
      for the maxillofacial region growth and development.

PMID- 15160103
TI  - [The prosthodontic treatment of 42 patients with dentition defect after MTM
      correction]

PMID- 15160104
TI  - [Effects of potassium oxalate with fluoride gel on dentin hypersensitivity]
AB  - This study observed the potassium oxalate including fluoride gel on the reduction
      of dentin hypersensitivity both in clinic and in laboratory.The results of the
      clinical treatment showed that this gel was statistically significant in reducing
      dentin hypersensitivity when the teeth treating by the gel for 4 minutes.The
      results of the scanning electric microscope(SEM) research indicated that the gel
      could create micro-globed particles deposition on the dentine surface.These
      particles have the ability to block the dentinal tubules and to decrease dentin
      hypersensitivity.In conclusion,this gel is an effective and safe topical agent
      for dentin hypersensitivity treatment.

PMID- 15160105
TI  - [The clinical observation of tetracycline stained teeth covered by composite
      resin veneer induced of secondary gingivitis]
AB  - Using gingival index,sulcus bleeding index and plaque index of 765 tetracycline
      stained teeth covered by composite resin veneer after 1/2-3 years were
      observed.It was found that the incidence of gingivitis was over 60%.The
      reexamination after three months later showed that the three indexes were
      significantly improved by grinding teeth proper and teaching standard brushing
      method.

PMID- 15160106
TI  - [Study on inspection method of anaerobes in periodontal pockets]
AB  - This paper used two methods only use non-selective medium(CDC) and together with
      seven selective mediums(VS CS BS AS FS ES LS) to inspect anaerobes in periodontal
      pockets.The results showed that Gram-negative anaerobes were the predominant
      microflora of periodontitis.The method of CDC together with selective mediums was
      founded much simpler and faster,more valuable than the method of only use non
      selective medium.It is illustrated that CDC added antibiotics or chemicals to
      make selective mediums was prepared convenience and was suitable for growth of
      relative anaerobes.But it is still necessary to establish much more,more special,
      more reliable selective or identical mediums.

PMID- 15160107
TI  - [Rapid identification of anaerobes in periodontics with computer]
AB  - It has documented that anaerobe has played important roles in the progress of
      periodontitis.Recently,the detection of its pathogens has caught more and more
      attention.This study has sieved physiological and biochemical reactions of more
      than 80 species anaerobes related to periodontics,selected the reactions with
      identifying significances to form a system,and identify bacterium according to
      their differences of the results to the selected reactions.The results of each
      bacteria is expressed with decimal number.then transfer it into the decimal
      number.So the decimal number represents the results of the bacteria to the
      selected reactions and represents a certain bacteria.The profile that the
      bacterium correspond to the numbers is designed.When the bacteria is
      identified,on the basis of its Gram stain,morphology and oxygen-tolerance,using
      compling program,the computer with suggest the reactions to be finished.After the
      reactions have been completed,input the produced number to the species of the
      indentified bacteria will be known.

PMID- 15160108
TI  - [The clinical analysis of 39 cases of oral mucosal hyperplasia]
AB  - This study was reviewing in analysed the clinical,histopathological and treatment
      features of 39 cases suffered in oral mucosal hyperplasia.It definited the sorts
      of disease which may be malignant changed and the histopathological grading
      criteria of hyperplasis.The different treatment methods were administered
      according to the different grade of the malignant change.The results of the post
      treatment observation showed that the drug method only be fit for the cases
      suffered slight hyperplasia without nuclei differentiation.

PMID- 15160109
TI  - [The formation of experimental periodontitis of Guinea pig]
AB  - This investigation was used silk suture and high sugar to study the formation of
      experimental periodontitis.The results showed that the gingival index(GI) and
      periodontal deep(PD) of all experimental Guinea pig were increased in the first
      week.There were more lymphocytes and plasmacytes in gingival proper layer in the
      second week.The plasmacytes and macrophages in gingival proper layer were
      increased much more in 4th week and alveolar bone was absorbed less,and there
      were more osteoclasts lying in resorpted area of alveolar bone.In the 8th
      week,the alveolar bone were resorpted more severe.There were more osteoblasts in
      the resorpted alveolar bone area besides the osteoclaste.The lysosome and
      endoplasmic veticulum in lymphocytes were increased.The osteoclasts near
      resorpted alveolar bone had several nucleus,and there were more lysosome
      chondriosome and endoplasmic veticulum,and the osteoclasts activity were
      increased,which suggests that silk suture and high sugar can form experimental
      periodontitis to Guinea pig and the formation time of experimental periodontitis
      was in the 4th week later.

PMID- 15160110
TI  - [Periodontal regeneration via artificial membrane induction: A review]

PMID- 15160111
TI  - [The immunoactive cells in lesions of oral lichen planus]

PMID- 15160112
TI  - [The mechanism of cellular infiltration in lichen planus and the up to date
      advances: Literature review]

PMID- 15160113
TI  - [Safely removal of the crown and bridge with untrasonic scaler]

PMID- 15160114
TI  - [Treatment of Non-Hodgkin's disease of the head and neck with Peplimycin: Short
      term follow up results]

PMID- 15160115
TI  - [Treatment of malignant fibrohistocytoma of the oral and maxillofacial region:
      Clinical analysis]

PMID- 15160116
TI  - [Acquired toxoplasmosis cervical lymphadenitis: Report of 6 cases]

PMID- 15160117
TI  - [Treatment of periodontal diseases with metronidazole mucosal adhesives: Clinical
      results]

PMID- 15160118
TI  - [The application of temporary crown and bridge for fixed prosthetic restorations]
AB  - The preparation of teeth for fixed prosthetic restoration needs the temporary
      restoration for various reasons.Once the enamel has been removed,a vital tooth of
      the sensitive dentin is exposed to the oral environment. If left unprotected
      teeth,the patient would experience a significant amount of sensitivity to the
      various stimulations to which the tooth is exposed.In addition,exposed dentin is
      much more susceptible to caries than enamel is.The prepared tooth is also lacking
      contact mesiodistall as well as occlusally with its counterparts in the
      dentition.It is not uncommon for the prepared tooth to drift mesially or distally
      or to extrued in an occlusal direction.This movement would,of course,cause
      problems in seating the final restoration.Temporization also allows for the
      testing of both the esthetic and functional design of the final restoration.The
      paper showed some fabrication methods for temporary crown and bridge and
      discussed the effect on the temporary crown and bridge and its needs for design.

PMID- 15160119
TI  - [Treatment of children recurrent parotitis dominated by immunotherapy]

PMID- 15160120
TI  - [One-stage surgical procedure of adult cleft palate with dentofacial deformity]
AB  - 2 cases with primary adult cleft palate combining severe dentofacial deformities
      were undergone one-stage procedure of modified Le Fort I segmental osteotomy and
      Furlow's double reserving Z plasty,and with with satisfactory clinical
      effectiveness.Follow-up results show that the one-stage procedure is not only
      reducing treatment time and period,but also correcting velopharyngeal function.

PMID- 15160121
TI  - [Thyroglossal fistula concomitant with micro-carcinoma of the thyroid gland:
      Follow up of one case for 13 years]

PMID- 15160122
TI  - [The measurement of EMG and deglutition pressure after glossal reconstruction]
AB  - Newly designed computer system (SAMP-EMG) was utilized,to measure the myoelectric
      signal in each region of the 100ms integral values and do the power spectral
      analysis in 10 normal people and 20 patients.At the same time,the pressure of
      deglutition was determined with the liquid pressure conducting electronic
      device.The results were :1.In normal EMG,the myoelectric power in anterior tongue
      is the highest,that in the margin of the tongue is the second,that in dorsum
      central area is the lowerest;2.There in no effective myoelectric signal detected
      in any kind flap;3.Normal swallowing pressure is 21.1+/-5.7kPa,the average value
      of FA is 10.3kPa,PM is 10.8,GC is 14.6.

PMID- 15160123
TI  - [Selection of approach and understanding of application in deep Over-Bite cases
      treated by Edgewise technique]
AB  - There are many approaches to open deep over bite with edgewise technique.As far
      as the three clinical pictures of deep over-bite are concerned,this article
      indicates that the extrusion and intrusion of teeth should be treated differently
      according to the technique of malocclusion-forming.It also makes a preliminary
      exploratory and analyse on the selection of commonly used approaches and personal
      understanding of clinical application.

PMID- 15160124
TI  - [Radiographic investigation of idiopathic osteosclerosis of jaws]
AB  - Full-mouth radiographs of 1321 patients were examined for the presence of
      radiopacitics that could not be attributed to any known sources of bone
      formation.A total of 75 patients exhibited these foci of idiopathic
      osteosclerosis.The incidence of disease is 5.7%,including SIO 46.3%,PIO 37.5%,IIO
      16.2%.The majority of the opacities were found in the mandible,especially from
      the mandibular first premolar to first molar region(65%).The lesion was most
      prevalent in the first three decades of life.

PMID- 15160125
TI  - [Treatment of fractured crown and crown with root in 245 cases]

PMID- 15160126
TI  - [Psychologic inversigation of parents of patients with congenital cleft palates
      and lips]
AB  - The parents of 100 patients with congenital cleft palates and lips were
      investigated psychologically.The results showed that the treatment was very
      urgent,In spite of poor knowledge in etiology and treatment.The effectiveness
      between patient and relation of parents,family was smaller than than that in
      abroad,and psychologic status was more stable.By investigation,the key of
      treatment in time was emotional activity of patients during systemic treatment.We
      suggested that it be necessary for patients to undergo psychologic training
      schedularly just after baby-patient-born.It made the parents to know that the
      function and emotional health of patient were ideal,by sysemic treatment via
      multi-subjects,the results of profile.

PMID- 15160127
TI  - [An experimental study on the HA-coated zirconia ceramic material for an
      endosseous implant]
AB  - HA layer is sintered onto the surface of zirconia ceramic material.These column
      like composite implants and titanium implants were inserted into the femurs of
      the dogs.The speciments were taken at the third month after operation,and the
      shear strengths between the implants and bone were measured.The undecalcified
      bone section containing the composite ceramic implant were cut for light
      microscopy,scanning electron microscopy and elemental analyses of C,P and
      Zr.Mechanical testing results revealed that the attachment strength of HA-coated
      zirconia samples is more stronger,as companied with the titanium
      samples.Histologic evaluations of the undecalcified specimens showed that
      extremely close juxlaposition of bone to HA-coated zirconia ceramic implants was
      seen.

PMID- 15160128
TI  - [A biomechanical investigation of Ha-coated ceramic implant]
AB  - Two samples of Ha-coated ceramic implants of which sintering temperatures were
      850 degrees centigrade,1050 degrees centigrade respectively,were prepared.Pure
      titanium implant of the same size was accomplished using a transcortical implant
      model in adult Mongrel dogs.Follow-up periods were 1,3 and 6 months.The results
      in vivo were evaluated using push-out tests and scanning electron
      microscope.There were significant differences in push-coated ceramic implants and
      pure titanium implants,especially for the 1 and 3 months follow-up period.SEM
      investigation of the interface after push-out test showed for the HA-coated
      ceramic implants to be fractured in the coating layer and for the Ti-implant to
      be fractured at the implant-bone interface.

PMID- 15160129
TI  - [A contour and mineral content comparison of vascularized and non-vascularized
      bone grafts]
AB  - This study made a comparison between vascularized bone graft (VBG) and non
      vascularized bone graft (NVBG) in mandible of canine by using electron computer
      to assess the contour of grafted bone and measuring the mineral contents. On the
      3rd, 5 th, 7 th, 15 th postoperative day, the contour of VBG and NVBG were
      similar and all of them kept the original contour. On the 30 th,60th,90th,180th
      postoperative day, VBG remained the original contour, but the contour of NVBG
      became thicker obviously than that of VBG for the remained cortical bone(most of
      which was resorbed) were enveloped with a lot of new bone. The kind of resorption
      of NVBG cortical bone in our study was characterized by extensive resorption on
      the surface just like nibbling of silkworm, unlike "tunnel" described in the
      literatures. There were no statistically differences between mineral contents of
      VBG and that of NVBG.

PMID- 15160130
TI  - [The use of red bone marrow in bone grafts]

PMID- 15160131
TI  - [Surgical treatment of internal derangement of the temporomandibular joint:
      Literature review]

PMID- 15160135
TI  - [Management of deep caries: New concept]

PMID- 15160133
TI  - [The influence of orthodontics on the enzyme activity and distribution in the
      periodontal tissues]

PMID- 15160132
TI  - [A comparative study of the teeth, dentition and occlusion between the Chinese
      and Japanese adults]

PMID- 15160134
TI  - [The possibility of growth hormone locally effecting on the alveolar bone]

PMID- 15160136
TI  - [The occlusal relation of the anterior teeth in the complete denture with normal
      jaw position : Re-examination]

PMID- 15160137
TI  - [Clinical application of visible light curing composite resin]

PMID- 15160138
TI  - [Psychological nursing of pre-school children receiving endodontic treatment]

PMID- 15160139
TI  - [The surgical management of true ankylosis of the temporomandibular joint:
      Technical notes]

PMID- 15160140
TI  - [The clinical significance of saliva beta(2)-m in patients with head and neck
      tumors]
AB  - The detection of serum beta(2)-microglobulin is presently used as a marker for
      malignant tumors.The present paper reports that the quantity of beta(2)
      microglobulin in the saliva from patients with head and neck tumors was detected
      by radioimmunity.The results indicates that the amounts of beta(2)-microglobulin
      in the saliva of patients with benign tumors(1.58micro/ml) were significantly
      lower than ones of patients with malignant tumors(2.89micro/ml),but similar with
      ones of normal patients(1.68micro/ml). beta(2)-microglobulin had the specific
      immunogenecity and was possibly linked with immunity.The cells of malignant
      tumors excreted relatively higher amounts of beta(2)-microglobulin.This might
      result from t he synthesization of the cells of malignant tumors and the increase
      of excreted beta(2)-microglobulin,or the direct entry of beta(2)-microglobulin
      excreted in the malignant tumors at head and neck into saliva and the
      infiltration of tumor cells into saliva and infiltration of tumor cells into the
      salivary glands.beta(2)-microglobulin in saliva appeared with serum.Thus,The
      detection of beta(2)-microglobulin in saliva is considered as a supplementary
      method for the diagnosis of tumors.

PMID- 15160141
TI  - [Evaluation of velopharyngeal function after later surgical repair of cleft
      palate. ]
AB  - This study detected 60 cases of patients of later surgical cleft palate repairing
      with different operative procedures,based on nasopharyngeal fiberscope and image
      processing detective system of nasopharyngeal function.They were divided into two
      groups,30 cases with Furlow's double reversing Z plasty,and others with
      traditional palatoplasty.The results were as follows:the type of velopharyngeal
      closure with later palatoplasty mainly were circus,semi-circus,and the rate of
      operative success only was 46.6%,which was lower than other reports.Author
      described that compensation of lateral and posterior pharyngeal wall made the
      type of velopharyngeal closure.The elder the age,the more the compensation is.For
      the late cleft palate repair,although the variable surgical procedure made a
      condition for speech improvement, patients with later cleft palate repair still
      can't improve their phonation.

PMID- 15160142
TI  - [Clinical analysis and treatment of 68 spaced dentition cases]
AB  - One of the characteristic feature of normal occlusion is arch continuity, as
      expressed by proximal contact between all teeth in each dental arch.The dental
      arches of a consider able number of individuals show space between some,or even
      all,of the teeth.Such dental arches are know as spaced dentition.It is
      detrimental of arch integrity, esthetics and normal dental function.The purpose
      of this article to study distribution according to sex and age,number and
      location of the spaces,their etiology and principle of orthodontic treatment.In a
      random sample of 68 cases of the participating patients who is space greater than
      0.5 millimeter between the proximal surface of adjacent teeth.The samples were
      divided into three age groups, the exact width of each space was measured by
      calipers in table.

PMID- 15160143
TI  - [Clinical application of cluster analysis in repairing prosthesis ears]
AB  - Along with developments and progresses of microsurgery,plastic surgery became
      very often used method to reconstruct orofacial defects,but for missing ears the
      prosthesis methods are still a better way comparing surgery The main merits are
      :no wound,short treatment time,100% success rate,easily figure established.For
      simplified steps and saving time in the procedure of making prosthesis ears.300
      different types ears from recording cases models are analysed and special
      different type wax-up ears and special models are made to provide different
      patients as needing for selection.

PMID- 15160144
TI  - [Survey of dentomaxillary deformities in 1032 middle school students]

PMID- 15160145
TI  - [Brachial cyst and fistula: Clinical analysis of 55 cases]

PMID- 15160146
TI  - [Study on the biocompatibility of commonly used root canal filling materials]
AB  - The biocompatibility of commonly used four endodontic sealers and three brands of
      gutta-percha was studied by cell attachment experiment in vitro and SEM
      technique.The results indicated that all the materials tested had significant
      cytotoxicity.Clinically,in order to avoid irritrating periapical tissue
      mechanically and reduce cytotoxicity,overfilling should be avoided when possible.

PMID- 15160147
TI  - [Neutrophils and monocytes in gingival epithelium]
AB  - Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal
      gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival
      bacteria were quantitated and analyzed,The results showed that the numbers of PMN
      within either pocket epithelium or oral gingival epithelium in JP were
      significantly lower than in AP and G.The amounts of PMN in AP were much larger
      than other three groups.Positive correlation between the number of PMN in
      sulcular pocket epitelium and the motile bacteri of subgingival plaque was
      demonstrated by correlation analysis.Monocytes mainly presented in deep pocket
      and junctional epithelum which were stained by NAE method,however very few
      Langhans cells were seen in these areas.

PMID- 15160148
TI  - [A study of prostaglandine E(2) level in root canal fluid of patients with
      periapical lesions]
AB  - It has been reported that there is close relationship between prostaglandine
      E(PGE) and the pathogenesis of periapical lesions, In this study the root canal
      fluid(RCF) of 35 cases with acute,chronic and convalescent periradicular lesions
      were collected with assessed by the method of radioimmunoassay.The results
      showed:RCF-PGE(2) levels were increased with the severity of periapical
      lesion(P<0.01).The PGE level was highest in acute periradicular lesions,middle in
      chronic,and lowest in convalescent.RCF-PGE(2) levels were significantly different
      between either two groups of the three groups of patients(P<0.01-0.05).This study
      repeatedly proved that PGE(2) has certain effect in pathogenesis of periapical
      lesions and it is meaningful in guiding clinical therapy.It was also pointed out
      that RCF is one of worthwhile samples in the study of periradicular lesion.

PMID- 15160149
TI  - [The effects of fibronectin on DNA synthesis and ultrastructure of periodontal
      ligament cells]
AB  - Microspectrophotometer and transmitted electron microscope (TEM) were used to
      study the change of DNA synthesis and ultrastructure after fibronection(FN) acted
      on cultured periodontal ligament cells (PDLC).The results showed that the data of
      nuclus area,nuclus total absorbs and nuclus mean absorbs of PDLC in FN group was
      higher than control(P<0.01).Under the TEM we observed that in FN group there were
      more euchromatin in cell nuclues and more organ cells such as
      microfilaments,chondriosomes and endoplasmic reticulum in cytoplasm.It suggested
      that FN can accelerate periodontal regeneration by promoting DNA and protein
      synthesis of PDLC.

PMID- 15160150
TI  - [Changes of enamel intake of fluoride amount while PH and fluoride concentration
      varies]
AB  - The four enamel pieces,which are from one bovine tooth,are treated individually
      by 2.7% NaF gel(pH4),2.7% NaF gel(pH7),1%NaF gel (pH7.0) and the control group
      gel.The fluoride amount in enamel pieces is measured by fluoride electrode.The
      aim of present study is to observe the changer of enamel intake of fluoride
      amount when the pH and fluoride concentration varies.In results the most fluoride
      amount in enamel pieces treated by 2.7% NaF gel(pH4) is measured.The more
      fluoride amount is measured in group of 2.7%NaF gel(pH7) than 1% NaF gel
      (pH7).The Results show lower pH and higher fluoride concentration can increase
      more fluoride amount in enamel.

PMID- 15160151
TI  - [The safety of mercury alloy: A public concerned problem]

PMID- 15160152
TI  - [The mechanism and correction of overbite of the anterior teeth]

PMID- 15160153
TI  - [Controversies over the relation between maxillary and mandibular basal bones]

PMID- 15160154
TI  - [The application of post-core-metal fused ceramic crowns in esthetic restoration
      of the anterior teeth]

PMID- 15160155
TI  - [Reverse Z-plasty for unilateral cleft lip repair]

PMID- 15160156
TI  - [Survey and follow up outcomes of lip smoke patch in specified population]

PMID- 15160157
TI  - [Teeth replantation after resection of recurrent epulis: Report of 12 cases]

PMID- 15160158
TI  - [Oral and maxillofacial injuries; Clinical analysis of 325 cases]

PMID- 15160159
TI  - [Study of the peripheral T-subtype and its function in juvenile periodontitis]

PMID- 15160160
TI  - [Intraoral removal of deeper calculus in the duct of submandibular gland]

PMID- 15160161
TI  - [Combined surgery with radiotherapy for carcinoma of the tongue: Clinical
      outcomes]

PMID- 15160162
TI  - [Extraction of the mandibular third molar with turbine bur:Retrospective study of
      548 cases]

PMID- 15160163
TI  - [Treatment of Bell's palsy: Report of 36 cases]

PMID- 15160164
TI  - [Behavioral and psychological observation of children during orthodontics]

PMID- 15160165
TI  - [The commonly used abbreviations and their significance: II. The dental journals
      and main relevant medical journals]

PMID- 15160166
TI  - [Cases study on occurence of ankyloglossi and its effect on pronouncing clarity]
AB  - Occurence of ankyloglossi and its effect on pronuncing clarity has not been
      reported in detail at home and abroad.Academic circles have defferent opinions on
      it till now.This article describes the occurrence of ankyloglossi and its effect
      on pronouncing clarity,based on the sample investigation made on three different
      age groups children(3,000 children).It is found that younger children have higher
      occurrence of ankyloglossi,but which has little influence on pronouncing
      clarity.Pronouncing clarity mainly depends on the increase of age and the ripe of
      language ability.

PMID- 15160167
TI  - [Lower lip biting habits and malocclusions]
AB  - In studying the cases of lower lip biting habits,we analyse and discuss its
      malocclusion and its orthodontic principle. It is indicated that prolonged lower
      lip biting habits always lead to overjet malocclusion,however,the mechanism by
      which overjet malocclusions are caused is different.We correct the malocclusions
      by the combination of lipbumper and removable,functional or fixed appliances to
      get the best results,depending on individual's age and the type of malocclusion.

PMID- 15160168
TI  - [The study of assessing methods for velopharyngeal function in patients with
      operated cleft palate]
AB  - This paper describes the study and quantitative analysis of velopharyngeal
      function in 103 patients with operated cleft palate using NPF,vedio-camera system
      and computer.The percentange of semi-circluar and circular closure patterns after
      surgery was distinct higher in VPI group than in VPC group,but coronary closure
      pattern was significant lower in VPI group than in VPC group(P<0.05).We compared
      the results of different operative age by VPI after surgery.The results showed
      that postoperative RVPI was in direct proportion to operated age.VPI in the group
      less than 3 years of age.VPI in the group less than 3 years of age was 28.57%,but
      in the group of over 7 years of age was 96.43%.Both showed significant
      difference(P<0.01).

PMID- 15160170
TI  - [Measurement of the Spee's curve and cuspid height in patients with overbite]

PMID- 15160169
TI  - [Tongue reconstruction with platysma myocutaneous flap: Reportof10 case]

PMID- 15160171
TI  - [Discussion of the treatment of Formocresol (FC-ZOE) and Glutaradehyde (GA-ZOE)
      for pulpitis and periapical disease on primary teeth]
AB  - This study was discussed of the treatment of FC-ZOE and GA-ZOE for pulpitis and
      periapical disease on primary teeth.The post-operation observation was from 18 to
      24 months.The result demostrated that the treatment for pulpitis is good,but for
      periapical disease is not satisfying. Ga-ZOE is effective as a fixing agent of
      devitalization for gangrenous root canal,and it was ineffective as an aseptic
      agent for infective root canal.FC-ZOE was disadvantage as a filling agent of root
      canal.

PMID- 15160172
TI  - [Analysis of 28 clinical cases and bone in stress around every tooth with
      pericementitis caused by occlusal trauma]
AB  - 28 cases of pericementitis on occlusal trauma were observed,treated and followed
      up for 2 years;The bone in stress around every involved tooth was analysed
      according to the stress analysis by three demensinal photoelastic models loading
      excessive occlusal forces in various direction and coincided with the area of
      abnormality on the tooth radiograph.The result showed that the present methods of
      examination and treatment for tooth with traumatic pericementitis could diagnose
      exactly and cure effectively this disease;the rate of cure for 2 years was
      86.7%,subtle occlusal adjustment by 3-4 appointments could maintain stable
      curative effect.It is suggested that clinicians should pay more attention to
      discover and treat both with traumatic pericementitis,the earliest clinical
      manifestation of both injury in occlusal trauma in order to protect them from
      severe injury in occlusal disharmony as well as periodontal trauma.

PMID- 15160173
TI  - [Clinical results of restoration of teeth defects with polycarbonate crown]

PMID- 15160174
TI  - [A study of absorbed x-ray doses and protection to critical organs of the head
      and neck during siaglography]
AB  - A tissue equivalent phantom was used in the study and absored x-ray doses.It
      measuring for some important organs of head and neck by four routive sialography
      methods (panoramic conventional x-ray radioagraphy,tomography,fluoroscope,CT) and
      also the X-ray absorbed doses of thyroid and len when lead containing loop and
      spectacles of head containing glass were used for prevention.All the data were
      processed statistically and a compartive study of absorbed x-ray doses of four
      sialography methods:Doses of submandibular gland were higher in CT,tomography and
      fluoroscope among them,CT was the highest indicating that it was superior to
      other methods for accurately locating that it was superior to other methods for
      accurately locating the within-gland tumor.Fluoroscope will be use more
      frequently in clinic,because it can observe the living gland panoramic and normal
      radiography can be used routinely because they had the minimum doses in measured
      organs.2.The absorbed x-ray doses of len and thyroid decreased by 93%-% when
      prevention was taken in CT or fluoroscope,65%-85% doses was decreased in normal
      radiography or panoramic with prevention.

PMID- 15160175
TI  - [Study on the apical sealability of warm lateral condensation techniques]
AB  - An apical leakage test and a visible light spectrophotmetric analysis were
      performed to compare the apical sealability of warm lateral condensation and
      conventional lateral condensation techniques.The results showed that warm lateral
      with sealer delivered best sealability.It was superior to warm lateral without
      sealer(P<0.05) and conventional lateral condensation technique(P<0.01).Because of
      its inconvenient operation causing by native-made putta-percha,it is difficult to
      use warm lateral condensation technique widely in our country.

PMID- 15160176
TI  - [A biomechanical study of the human periodontal ligament]
AB  - The structures and mechanical properties of the normal human periodontal
      ligament(PDL) were investigated by VDA measuring system through the microscope.It
      was found that the mechanical properties of PDL is not linear.Its mechanical
      properties are depending on its fibrous properties,directions and components.The
      linear and index relationships of the tensile and compression stress-strain curve
      of PDL can be divided into 6 segments.The strain changes and moduli of every
      segment were calculated.The relationship between periodontal function and the
      variation law of stress-strain is investigated and its clinic value is shown.

PMID- 15160177
TI  - [An analysis of the cephalometric investigation of the Chinese craniofacical
      pattern in neolithic]
AB  - Craniofacial morphology provides valuable data for determining races and ethnic
      groups and evolutionary adaptedness of prehistoric human population.Craniofacial
      investiation yield reliable clues to the ethnic of skeletal series,because
      craniofacial traits can be evaluated in different ethnic groups.The neolithic
      human skull of Chinese in this study are about 6000 years ago (B.C.4750
      3700).Authors studied the neolithic human skull of Chinese with cephalometric
      radiography.

PMID- 15160178
TI  - [The value of finite element analysis in the study of biological mechanics in
      orthodontics]

PMID- 15160180
TI  - [Advances in mandible reconstruction with revascularized composite free flaps:
      Review of the literature]

PMID- 15160179
TI  - [Treatment of antral perforation using mixed zinc oxide paste: Report of 2 cases]

PMID- 15160181
TI  - [Induction operation of the dental inherent sense: An introduction]

PMID- 15160182
TI  - [Paramenia caused by injection of triamcinolone: Clinical analysis]

PMID- 15160184
TI  - [Clinical analysis of 20 patients with carcinoma of the lip]

PMID- 15160183
TI  - [Oral survey in children of three different nationalities in Menghai county of
      Yunnan province]

PMID- 15160185
TI  - [The use of finished crowns in prosthodontics]

PMID- 15160187
TI  - [TNM staging and classification: III. Head and neck cancer(continued)]

PMID- 15160186
TI  - [Pleomorphic carcinoma of the salivary gland: Clinicopathological analysis in 53
      cases]

PMID- 15160188
TI  - [Comparison of acoustic images and pathologic findings in 51 patients with
      salivary masses]

PMID- 15160189
TI  - [Observation on revascularization of free flaps with the technique of
      microvascular corrosion]
AB  - In order to study the process of revascularization of free flap bilateral dorsal
      auricular free flaps of 18 Newzealand rabbits were completed and investigated
      with the technique of microvascular corrosion casting at 2,4,7,10 days and 2,4
      weeks postoperatively.It was discovered that scarce neovascularity appeared
      around the margin of flap before 2 weeks following transplantation and extensive
      revascularization occured at 3 weeks postoperatively.The capillaries connected
      through their netword expansion while central artery and vein formed
      recirculation by means of multiple point anastomoses of the "vascular buds"
      sprouting up at both ends of vessels.

PMID- 15160190
TI  - [Fixed orthodontic treatment of 32 impacted anterior teeth]

PMID- 15160191
TI  - [The effect of FN(fibronectin) on invasion and metastasis of human acinic cell
      carcinoma cell strain of the salivary gland]
AB  - FN distribution in ACC-2 and high lung-metastatic ACC-M cells was studied with
      immunohistochemical staining.There were less FN found in ACC-2,but much more FN
      were observed in the highly metastatic clone Acc-M.In vitro motility of two cell
      lines was measured by Boyden chamber.With the presence of exgenous FN,Acc-2
      became activated with a higher migration rate.The cell adhesion test showed that
      Acc-2 had stronger ability of adhesion than Acc-M with the presence of FN.The
      result suggested FN may play a vital role in the invasion and metastasis of ACC.

PMID- 15160192
TI  - [The pre-postoperative polysomnographic evaluation on the patients of TMJ
      ankylosis with OSAS]
AB  - Passing by the comparative studies on the polysomnogram of the patients of TMJ
      ankylosis with OSAS pre-and-postoperation,the result showed the patients' AI
      (Apnea Index;AI) has been decreasing,SaO(2) during sleep get to rise,and the
      method combining TMJ reconstruction and orthognathic surgery is effective to the
      patients.

PMID- 15160193
TI  - [Comparative study of grind-resistance,corrosion,and adhesion of dental plaque on
      gallium and amalgam alloy's filling]
AB  - The adhesion of plaque on dental restorative between gallium alloy and amalgam
      alloy were compared.The results showed that plaque index and plaque account of
      gallium alloy was higher than those of amalgam,there was statistically
      significance(P<0.01).It was possible that secondary caries of gallium alloy's
      restorative may be higher than those of amalgam.One the other hand,the surface of
      restorative polished was necessary to improve the adhesion of plaque and to
      prevent the secondary caries.

PMID- 15160194
TI  - [Clinical study on the recovery of sensory function in tissue flaps repairing the
      defect of oral and maxillofacial region]
AB  - The recovery of sensibility in 29 cases non-neurolorized tissue flaps and 4 cases
      neurolorized flaps have been studied clinically. The results showed that:the
      sensory function started to return from 3 months after operation and recovered
      gradually.Pain sensibility recovered first,followed by tactile,thermal and two
      point discrimination sensibility.The recovery usually occured from edge to centre
      of the flap 2-3 years after operation,about 65.5% nonneurolorized flaps obtained
      good recovery of sensibility.The recovery rate of pain,tactile,thermal and two
      point discrimination sensibililty was 64.7%,64.7%,53.0% and 23.5%
      respectively.Flaps recovered better than myocutaneous flaps.The recovery of
      sensibility of the neurolorized flaps occurred early and quickly.All 4 cases
      obtained excellent sensory recovery including two-point discrimination
      sensibility.The results suggest that:the sensory function of tissue flaps come
      from not only surrounding,but also deep tissue,any factor that can cause decrease
      of quality and quantity of regenerated nerve endings will inhibit flap from
      recovering its sensory function.

PMID- 15160195
TI  - [The value of the different radiological examining methods in caries diagnosis]
AB  - This in vitro study compared the results of clinical examination (abbreviation
      CE) and the three radiological methods (i.e RVG-radiovisiography) on occlusal and
      proximal caries diagnosis,using pathological observation as the final
      standard.The results are:on occlusal caries diagnosis,CE provide the most
      accordant result to the pathological result.There are statistically significant
      differences between SR and CE,BW and CE.1st suggests that to occlusal caries
      diagnosis,CE is still a convenient and efficient way.On proximal caries
      diagnosis,there are statistically significant differences between SR and CE,BW
      and CE.BW has the most coincident result with pathological one.

PMID- 15160196
TI  - [The immunohistochemical study to comparing PCNA and p53 expression in oral
      squamous cells carcinoma]
AB  - We have studied expression of the PCNA and p53 protein in oral squamous cells
      carcinoma by ABC immunhistochemical technique,and analyzed the characteristic
      about clinical pathological parameters and metastasis between them.This result
      showed PCNA expression were corrected with tumor grading,but not with tumor
      invasion.There was strong correlation between p53 over expression and tumor
      invasion and lymph node metastasis.p53 positive tumours have highly lymph node
      metastasis(60%),but p53 negative tumours have lower(29%).Overexpression of p53
      was found to be relatively higher,although not statistically significant in
      buccal mucosa than in other sites.p53 and PCNA may be an useful indication to the
      clinician to predict tumour behavior and prognosis.

PMID- 15160197
TI  - [The lymphoepithelial lesion in salivary glands:report of 25 cases]
AB  - This paper reported the results of the clinical observation and long-term follow
      up of twenty-five cases of lymphoepithelial lesion in salivary glands.It
      evaluated the name and character of this disease and investigated correlation
      between Mikulicz syndrome and Sjogren syndrome.Lymphoepithelial lesion were a
      course of the benign disease,and had character similar as tumors.It was liable to
      be diagnosed erroneously and should be treated according to principle of the
      tumor therapy in the salivary gland.

PMID- 15160198
TI  - [The establishment of the digital imaging analysis system on the lower
      maxillofacial soft tissue]
AB  - Soft tissue shape is an important parameter to evaluate the postprosthetic effect
      of facial profile.In this study,the technique of digital imaging analysis was
      used to transferring from imaging informations to digital information,and then
      these information were imputed to computer for capturing,measuring and
      analyzing.So far,a set of digital imaging analysis system relating to the
      speciality of prosthodontics has been established preliminarily,with the
      advantage of quantitative analysis,non invasion and accuracy.It will provide a
      new way for reconstructing vertical dimension of occlusion.

PMID- 15160199
TI  - [Analysis of the measurement on of the maxillofacial soft tissue's parameters
      association with vertical dimension]
AB  - The rehabilitation of vertical dimension of occlusion(VDO) exactly is one of the
      most important procedure for dental prosthesis in the field of prosthodontics.In
      this study,total of 19 subjects with normal range occlusion were selected.We
      measured 33 parameters relating to VDO of their facial soft tissue at
      intercusping position,with the technique of digital imaging analysis.The results
      as follows:we established a set of normal values of facial soft tissue
      parameters,which is suitable for the age group of 21-24 years old.It would
      provide an objective criterion for the rehabilitation of VDO.Also the normal
      values in this studies had been compared with other other studies,and it showed
      that the values of some parameters in our study,such as CH-CH',nasolabial angle
      were very close to oter data.Furthermore,it was found that both the position of
      the upper lip and the lower lip of the subjects were more anterior to that of
      white men,while the degrees of nasolabial and labiomental convexity were less
      obvious.

PMID- 15160200
TI  - [Computer-aided analysis of maxillofacial soft tissue simulating with vertical
      dimensions of 4 different types]
AB  - In this study,33 parameters relating to vertical dimension of occlusion(VDO) of
      19 subjects' maxilofacial soft tissue of four different vertical dimentsions(VDs)
      were measured.All of them were in intercusping position,with the technique of
      digital imaging analysis.The findings as follows:(1)A set of normal values of
      facial soft tissue's parameters of four different VDs was established,which was
      suitable for the age group of 21-24 years old.(2)When the VD was raised to the
      certain height(H4),it would affect the size of angle of the inferior soft tissue
      of lip distinctly,furthermore,the correlation analysis showed that there was a
      positive correlation between the variance of VDs would arouse the change of the
      inferior soft tissues of lip,especially its size of angle,is very correspondingly
      and obviously.

PMID- 15160202
TI  - [Orthognathic surgery for patient with deformity of the jaw and OSAS: Report of
      one case]

PMID- 15160201
TI  - [The use of double fixation in treatment of vertically fractured teeth]

PMID- 15160203
TI  - [The use of central volaris forearm flap in oral and maxillofacial
      reconstruction]

PMID- 15160204
TI  - [Removal of the intact fixed prosthesis with ultrasound appliance]

PMID- 15160205
TI  - [The direct bonding technique for brackets and related factors: Review of the
      literature]

PMID- 15160206
TI  - [Detection of immunoglobulin in the gingival sulcus fluid of pregnancy
      gingivitis]

PMID- 15160208
TI  - [The use of radiosensitizer in treatment of head and neck malignant tumors:
      Literature review]

PMID- 15160207
TI  - [Extreme mouth opening as pharmaceutical extra-central symptom:Report of 5 cases]

PMID- 15160209
TI  - [Advances in the study of indexes for periodontal diseases and their
      epidemiology: An overview]

PMID- 15160210
TI  - [Correlative analysis with proliferating cell nuclear antigen and
      bromodeoxyuridine on golden hamster carcinogenesis model]
AB  - The early diagnosis of carcinomatous conversion has special significance on
      increasing therapeutic effectivencess.Proliferating cell
      nuclearnatigen(PCNA),bromodexoyuridine(UrdU)(immunohistochemistry ways),and
      microscopic diagnosis were applied and observed on golden hamster cheek is pouch
      carcinogenisis model induced by dimethylbenzanthracene(DMBA) in order to seek
      simple,effective,leading and reliable diagnostic way.The results showed that
      three observable means had significant correlativity,and demonstrated that
      immunohistochemistry ways have practical value in diagnosis of carcinomatous
      conversion.This study suggests that PCNA and BrdU be more sensitive,simple and
      reliable,and hopeful methods of early diagnosis of carcinomatous conversion.

PMID- 15160211
TI  - [Morphological study on occlusal grove of mandibular molar of Chinese adults]
AB  - During human evolution,the morphology of mandibular molar occlusal grooves have
      changed from the pattern "Y" to pattern "+".Six types of occlusal grooves were
      classified as:Y5,Y4,+5,+5,X5 and X4. Using computer analysis,we get the
      result.(1)The rate of "Y5" in first mandibular molar is the highest,the rate of
      "X4" is the lowest.(2)The rate of "+4" in second mandibular molar is the
      highest,while the rate of "Y5" is the lowest. (3)The rates of each type groove
      between male and remale have no significant difference.Our conclusion coincides
      in the evolution of human mandibular molar,that is helpful to direct the clinic
      and anthropology study.

PMID- 15160212
TI  - [Calcium ion-selective miroelectrodes for measurement of free calcium in saliva]
AB  - In this paper, the free calcium concentration in saliva was measured and
      evaluated by the neutral carries ion-selective microelectrodes.The statistical
      results showed that there was no significant difference (the groups of
      all,P>0.05) between children and adult,between male children and female
      one,between caries-free and caries-active,and between interval of two weeks.The
      results suggested that caries might be no direct relation to the calcium
      concentration in children physiological saliva. Calcium ion-selective
      microelectrodes seems to be a good method for measuring free calcium in oral
      micro-sample fluid.

PMID- 15160214
TI  - [Clinical application study of intraoral high-level mandibular neurotomy:
      Reported of 19 cases]
AB  - Trigeminal neuralgia is a common disease in clinical practice. The recurrence
      rate after avulsion is relatively high. In order to reduce the recurrence rate,
      the author developed a new method and operated on 19 cases with intraoral high
      level trigeminal neurotomy based on 21 cases of adult human skull anatomy. The
      method is simple, safe and in good condition. The author emphasized that the
      proper management of the buccal branch during operation may have a close relation
      with the post-operative recurrence rate.

PMID- 15160213
TI  - [The clinical effects of tea polyphenol varnish on caries prevention]
AB  - The aim of the present research is observing the effects of tea polyphenol
      varnish on caries prevention.107 children were in treated group,their first
      deciduous molars and deciduous incisors were treated by tea polyphenol varnish
      twice each.Other 110 children in control group did not receive any treatment.Two
      doctors examined their dental caries and recorded dmft and dmfs befoe treated and
      one year after treatment.The results indicate that the new caries incidence of
      the first deciduous molars and deciduous incisors in treatment group decreased
      66% than that in control group.The results show that the new caries incidence of
      other untreated teethin treated group is lower significantly than that in control
      group.The effects of tea polyphenol varnish on preventing caries were more
      significant in deciduous molar than in deciduous incisor.The results also
      indicate that the effect of varnish is stronger in occlusal surface,and less in
      medial and distal surfaces of teeth.

PMID- 15160215
TI  - [Cyst of temporomandibular joint with two cases of clinical and pathological
      analysis]
AB  - In this paper,two cases of cyst of temporomandibular joint were reported.We
      studied eleven cases' literature combined with our clinical and pathological
      findings,including B typed ultrasonography, CT image and surgical management.We
      analyzed this kind of cyst from etiological pathological and clinical features
      and diagnostic therapeutic event.It is a very rare disease with the preferential
      incidence in woman.We suggested B typed supersonic exam be the first exam
      method,surgical removal is the best regime.But final diagnosis is depend upon
      biopsy.

PMID- 15160216
TI  - [Observation of clinical and pathological responses in short-term following
      immunochemotherapy for oral squamous cell carcinoma]
AB  - 24 patients with oral SCC in Stage T3 or T4 were randomly divided into two
      groups,and treated with two inductive therapies,13 cases of whom received an
      immumochemotherapy regimen(Sapylin 15 KE+CDDP 70mg/m(2)+VCR 1.4mg/m(2)+PYM 80mg,S
      PVP) and 11 cases,a chemotherapy regimen(CDDP 90mg/m(2)+VCR 1.4mg/m(2)+PYM
      80mg,PVP) as control.The clinical response and pathological effect after
      immunochemotherapy or chemotherapy were evaluated through the clinical
      measurement of tumor size and pathological examination of the specimen.The
      results showed that the rate of clinical and pathological responses in S-PVP
      group were 92.3% and 84.6%,respectively;and in PVP group,72.7% and 45.5%.There
      was a significant difference between two groups in pathological
      effect(P<0.05),which indicated that the S-PVP regimen in short-term was better
      than of inductive chemotherapy.It may be relatively objective and accurate in
      comparison with clinical investigation which could act as an important supplement
      to the evaluation of clinical response.

PMID- 15160217
TI  - [Effect on intratumoral T lymphocyte and its subset in oral squamous cell
      carcinoma following immumnochemotherapy]
AB  - The relative numbers of CD(3)(+),CD(3)(+),CD(8)(+) and HLA-RD(+) cells in the
      tumor tissue before and after inductive therapy was counted using
      immunohistochemical technique of Avidin Biotin-Peroxidase Complex(ABC),and then
      the effect on local immune cell following two different inductive therapies was
      comparatively analysed.The results showed that S-PVP therapy could result in
      significant increasing in numbers of CD(3)(+)and CD(4)(+) cells intratumorally as
      compared with pre-therapy(P<0.05),and in slignt increasing in numbers of CD(8)(+)
      and HLA-DR(+) cell,which is no significant difference between pre-and post
      therapy.In the PVP group,there was no significant difference in numbers of
      CD(3)(+),CD(4)(+),CD(8)(+) and HLA-DR(+) cells between pre-and post-treatment.The
      results suggested that T lymphocyte in the tumor site could significantly
      increase in numbers following the S-PVP therapy,and PVP chemotherapy did not
      obviously affect the local cellular immunity.

PMID- 15160218
TI  - [Yield and cytotoxicity of tumor-infiltrating lymphocyte(TIL) following
      immunochemotherapy]
AB  - Tumor-infiltrating lymphocyte (TIL) in the primary site of oral SCC treated with
      S-PVP of PVP therapy was collected respectively and its yield,that is calculating
      the amount of TIL per tumor tissue.The cytotoxicity of TIL against the
      target,Tca8113 was detected.The results showed that the yield of TIL in S-PVP
      group was three times over that in PVP group.At the ratio of 5 to 1 (effector to
      target) the cytotoxicity was 38% in S-PVP group and 32% in PVP group.There was no
      significant difference in its cytotoxicity between two groups.The results
      revealed that immunochemotherapy of S-PVP regimen for treating oral SCC had
      neither direct damage to tumor cell from the agents nor antitumor immune
      reactivity with BRM stimulating an increasing in numbers of TIL.

PMID- 15160219
TI  - [A comparative study of elastomeric chains force delivery properties]
AB  - In this study,four different kinds and three different length elastomeric chains
      were tested to compare their force delivery properties.It suggested that
      different kind and length chains should be selected to generate optimal
      orthodontic forces clinically.

PMID- 15160220
TI  - [Properies of orthodontic wires in simulated teeth alignment test]
AB  - In this study,methods were developed to test and compare leveling archwires that
      commonly used in domestic practice.The results showed that the stainless steel
      arch wires were stiff.The Ni-Ti wires and the wires with loops were flexible and
      could deliver more constant force.The 0.014 Chinese Ni-Ti wires demonstrated the
      superelastic property,but 0.016 Ni-Ti wire did not appear the same property
      before they generated 250g force.

PMID- 15160221
TI  - [Orthodontic wires in a simulated oral environment:change in mechanical
      properties]
AB  - In this study,some different kinds of orthodontic archwires were tested to
      evaluate the changes of their mechanical properties.The results showed that in
      oral environment,all wires suffered degradation of their properties:the force
      generating capacity decreased and the permanent deformation increased.The force
      generating capacity decreased and the permanent deformation increased.The force
      decay resulted mainly from the tooth movement.The deformation occurred within 7
      days.Chinese-NiTi alloy suffered less stress-relaxation and residual deformation
      than the stainless steel wires.Arch wires with vertical loops showed similar
      properties with NiTi,which could deliver more constant force.

PMID- 15160222
TI  - [Anterior teeth implants: Clinical experience]

PMID- 15160223
TI  - [Extraction of the impacted mandibular third molar: Clinical analysis of 126
      cases]

PMID- 15160224
TI  - [The use of modified pedicled pectoralis major myocutaneous flap in oral and
      maxillofacial surgery]

PMID- 15160225
TI  - [Method for measuring the suck stress in newborn and infant]

PMID- 15160226
TI  - [Mesio-distal fracture of the posterior crown and root: Analysis of the causes]

PMID- 15160227
TI  - [The periodontal features of commonly used animal models for study of periodontal
      diseases]

PMID- 15160229
TI  - [The step back procedure: An ideal method for root canal widening with better
      cleaning and contouring]

PMID- 15160228
TI  - [TWEED technique in orthodontics: Part III]

PMID- 15160230
TI  - [Diagnosis and treatment of desmoid tumor in maxillofacial region]

PMID- 15160231
TI  - [The use of threaded root canal retention pins in restoration of severe defects
      of the posterior crowns]

PMID- 15160232
TI  - [Treatment of infected deciduous root canal with Samyan (traditional Chinese
      medicine)paste: Clinical analysis]

PMID- 15160233
TI  - [Lateral exposure of the submandibular gland with gland pressing downward]

PMID- 15160234
TI  - Comparison of the effects of calcium loading with calcium citrate or calcium
      carbonate on bone turnover in postmenopausal women: reply.

PMID- 15160236
TI  - Putting it all together to predict extubation outcome.

PMID- 15160238
TI  - The ICNSS: incorporating family care into nursing workload assessment.

PMID- 15160237
TI  - Reply to the comment by Skrobik et al.

PMID- 15160235
TI  - Histidine-tryptophan-ketoglutarate solution for organ preservation in human liver
      transplantation-a prospective multi-centre observation study.
AB  - Based on experimental work and clinical small studies, histidine-tryptophan
      ketoglutarate (HTK) solution was found to be suitable not only for heart and
      kidney preservation but also for liver preservation. We decided, therefore, to
      use this preservation solution for clinical liver preservation in a prospective
      multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European
      centres, and the results of 214 patients with HTK-preserved organs were analysed.
      Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non
      function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient
      survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a
      univariate and a multivariate analysis PDF, early surgical complications and
      tendentiously severe infections (septicaemia, pneumonia, cholangitis) were
      identified as independent risk factors for graft and patient survival.
      Preservation with HTK can be regarded as an established alternative to
      preservation with University of Wisconsin (UW) solution when preservation times
      are short. Definitive assessment of the efficacy of preservation solutions
      requires further prospective randomised clinical trials that compare HTK and UW.

PMID- 15160239
TI  - Catheter-related infection in critically ill patients.
AB  - OBJECTIVE: To describe the incidence of the catheter-related local infection
      (CRLI) and catheter-related bloodstream infection (CRBSI) of central venous
      catheters (CVCs) and arterial catheters (ACs). DESIGN: Prospective, observational
      study. SETTING: A 24-bed medical-surgical intensive care unit of a 650-bed
      university hospital. PATIENTS: We included 988 consecutive patients admitted to
      the ICU during 18 months. MEASUREMENTS: The incidence density of CRLI and CRBSI,
      per 1000 catheter-days, of CVC and AC. RESULTS: Central venous catheters had a
      significantly higher incidence density of CRLI (4.74 vs 0.97/1,000 catheter-days;
      p<0.001) than ACs. Femoral venous access had a higher incidence density of CRLI
      than subclavian (13.15 vs 1.81/1,000 catheter-days, p=0.003) and than peripheral
      access (13.15 vs 2.30/1,000 catheter-days, p<0.001). Jugular venous access had a
      higher incidence density of CRLI (6.29 vs 1.81/1,000 catheter-days, p<0.001) than
      subclavian access. We found no significant differences in the incidence density
      of CRLI and CRBSI between the different AC accesses. CONCLUSIONS: In the CDC
      guidelines, catheter insertion at the subclavian site is recommended in
      preference to femoral and jugular accesses, and there is no recommendation about
      AC site insertion. Our data support these recommendations about CVCs. Because the
      AC infection rate was very low, our study suggests that the access site is
      probably not of major importance for this type of catheter.

PMID- 15160240
TI  - [Imaging diagnostics of ulnar wrist pain].
AB  - An exact knowledge of the value of different pictorial diagnostic techniques
      allows a focussed and rapid diagnosis of ulnar wrist pain. A prerequisite for the
      choice of the best possible method of investigation is an exact clinical
      examination. The basic examination involves conventional recording at both the
      centralised at the symptomatic levels. If there is a suspicion of occult bone
      lesion, finely focused, magnified graphics, CT or bone scintigraphy should be
      used, depending on both the problem faced and availability. For tissue or
      ligament lesions, stress graphics, movement studies or MRT, also with contrast
      media, should be used. Bone scintigraphy is a suitable method to differentiate
      between inflammatory tissue and/or bone changes.

PMID- 15160241
TI  - Genomic regions influencing resistance to the parasitic weed Striga hermonthica
      in two recombinant inbred populations of sorghum.
AB  - Molecular markers for resistance of sorghum to the hemi-parasitic weed Striga
      hermonthica were mapped in two recombinant inbred populations (RIP-1, and -2) of
      F(3:5) lines developed from the crosses IS9830 x E36-1 (1) and N13 x E36-1 (2).
      The resistant parental lines were IS9830 and N13; the former is characterized by
      a low stimulation of striga seed germination, the latter by "mechanical"
      resistance. The genetic maps of RIP-1 and RIP-2 spanned 1,498 cM and 1,599 cM,
      respectively, with 137 and 157 markers distributed over 11 linkage groups. To
      evaluate striga resistance, we divided each RIP into set 1 (116 lines tested in
      1997) and set 2 (110 lines evaluated in 1998). Field trials were conducted in
      five environments per year in Mali and Kenya. Heritability estimates for area
      under the striga number progress curve (ASNPC) in sets 1 and 2 were respectively
      0.66 and 0.74 in RIP-1 0.81 and 0.82 in RIP-2. Across sites, composite interval
      mapping detected 11 QTL (quantitative trait loci) and nine QTL in sets 1 and 2 of
      RIP-1, explaining 77% and 80% of the genetic variance for ASNPC, respectively.
      The most significant RIP-1 QTL corresponded to the major-gene locus lgs (low
      stimulation of striga seed germination) in linkage group I. In RIP-2, 11 QTL and
      nine QTL explained 79% and 82% of the genetic variance for ASNPC in sets 1 and 2,
      respectively. Five QTL were common to both sets of each RIP, wtih the resistance
      alleles deriving from IS9830 or N13. Since their effects were validated across
      environments, years and independent RIP samples, these QTL are excellent
      candidates for marker-assisted selection.

PMID- 15160242
TI  - [82-year old patient with hyperostosis frontalis, prognathism, makroglossia and
      cutis gyrata. Acromegaly].
AB  - We present a 82 year old female patient with typical acral enlargement. There
      were no signs of visceromegaly. Magnetic resonance imaging of the pituitary
      region showed a macroadenoma. Oral glucose tolerance test revealed missing
      suppression of the Human Growth Hormone (HGH), which could be achieved with a
      long acting somatostatin analog. A HGH suppressive therapy with a long acting
      dopamine agonist (Cabergolin) was induced. The patient died one year later
      following cardiovascular complications.

PMID- 15160243
TI  - [Best supportive care of pancreatic carcinoma].
AB  - The incidence of pancreatic cancer is about 10,000 cases a year in Germany. The
      role of surgery as a curative modality is limited. The 5-year survival for all
      stages remains less than 5%. Pain, cachexia, jaundice, nausea, fatigue and
      depression are frequent symptoms which reduce the quality of life for affected
      patients. Therefore, amelioration of symptoms is a major goal of palliative care.
      Chemotherapy may yield a moderate survival benefit. Gemcitabine is the drug of
      choice in metastatic pancreatic cancer. In locally advanced disease,
      radiochemotherapy can be considered. Different treatment strategies against
      molecular targets are currently tested in clinical trials.

PMID- 15160244
TI  - [Biologicals: a new therapeutic approach for inflammatory diseases].
AB  - The pathogenesis of inflammatory diseases is determined by a malfunction of the
      immune system. Up to now therapies have not been able to cure but to interfere in
      a more or less specific way with the immune function. The great increase of
      knowledge in immunology made it possible to develop new medications, which alter
      the immune system in a specific way. The advantage is the relative simple way of
      developing new medications by using monoclonal antibodies against specific
      antigens and testing the hypothesis in animal model and in small but clear phase
      II trials. Biologicals are similar or identical to human proteins and rarely have
      side effects, which exceed their interference with the immune system. Because of
      the clinical success of anti-TNF-therapies and the increased knowledge about
      immune mechanisms, biologicals are now used in various fields of medicine. This
      paper reviews data from biologicals that are either already approved or in an
      advanced stage of clinical testing.

PMID- 15160245
TI  - [Best supportive care of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some
      areas of the world. The major etiologic risk factors include toxins (alcohol,
      aflatoxin B(1)), hepatitis B and C virus infection as well as various inherited
      metabolic disorders. The prognosis of HCC patients is generally very poor with a
      5-year survival rate of less than 5%. The diagnosis is based on biochemical and
      imaging tests as well as histology. Therapeutic strategies include surgery
      (resection or liver transplantation) and non-surgical interventions, such as
      percutaneous ethanol injection or radiofrequency thermal ablation as well as
      transarterial embolization or chemoembolization. Radio- or chemotherapy are
      mostly ineffective. Therefore, the development and evaluation of novel HCC
      treatment strategies as well as the implementation of existing and the
      development of new measures to prevent HCC are of utmost importance. The better
      understanding of the clinical and molecular pathogenesis of HCC should lead to
      improved diagnostic, therapeutic and preventive strategies with the aim to reduce
      the incidence of HCC, one of the most devastating malignancies worldwide.

PMID- 15160246
TI  - Correlations between dentition anomalies and diseases of the of the postural and
      movement apparatus--a literature review.
AB  - From anatomic and functional aspects the stomatognathic system and the upper
      cervical spine are closely interlinked. Together with complex neuromuscular
      relationships, this gives rise to an important field of cooperation between
      orthodontics and orthopedics. The literature appeals for close interdisciplinary
      cooperation for patients with syndromes and for those with torticollis and
      scoliosis. Since orthopedic points of contact are obvious in these special cases,
      orthopedic aspects are now being taken increasingly into account in farther
      reaching studies. With the rising popularity of manual medicine, these aspects
      are being recognized from the orthopedic point of view too in terms of functional
      correlations and are being increasingly debated at international congresses and
      in the literature. Although relevant publications were initially confined to
      studies of moderate scientific interest or case reports, potential correlations
      have undergone scientific investigation in recent interdisciplinary studies.
      Despite the many clinical studies, no unequivocal recommendation can be given for
      basic conditions under which an orthopedist is bound to be consulted on patients
      with orthodontic findings. This literature review is aimed at providing an
      introduction to this still hotly debated issue.

PMID- 15160247
TI  - Abnormalities of the TMJ and the musculature in the oculo-auriculo-vertebral
      spectrum (OAV). A CT study.
AB  - The abnormalities covered by the generic term "oculo-auriculovertebral spectrum"
      (OAV) form an exceptional heterogeneous dysmorphic complex characterized by
      unilateral malformations of miscellaneous craniofacial structures. The aim of the
      present study was to analyze morphometrically the developmental deficits
      concerning the temporomandibular joints, the mandibular rami and the mastication
      muscles by comparing the affected with the non-affected side. The volume, maximum
      horizontal diameter, and trabecular bone density of the head of the mandible, as
      well as the ramus height were acquired from CT data of 16 patients suffering from
      this syndrome. The volume and maximal cross-sectional area of the masseter
      muscles and the pterygoid muscles were defined by quantifying CT data of nine
      patients. The skeletal parameters were evaluated with VoXim software. The
      comparison of the mandibular structures on the affected and on the non-affected
      side was based on the Wilcoxon signed rank test. The results recorded on the
      affected side showed that the TMJ volume was reduced by a mean factor of 7.98,
      and the spongiodensity of the head of the mandible by a mean factor of 1.33,
      while the mean reduction in ramus height was 14.89 mm. The muscle volumes on the
      affected side had also undergone a mean reduction of 9.10 cm(3). The CT-based
      data analysis proved to be an excellent tool for quantitative three-dimensional
      evaluation of both the skeletal and the muscular parameters.

PMID- 15160248
TI  - The angle between the Frankfort horizontal and the sella-nasion line. Changes in
      porion and orbitale position during growth.
AB  - AIM: The starting point of this study was the statement made in the literature
      that the angle between the two reference planes Frankfort horizontal (FH) and
      sella-nasion line (SN) changes relatively little during growth. The growth
      induced relocation of the orbitale (Or; anterior reference point of the FH) in
      relation to SN is known from implant studies, whereas the relocation of the
      porion (Po; posterior reference point of the FH) has been the subject of only
      little research. The present study was aimed at analyzing the factors
      contributing to the almost constant angle between FH and SN. MATERIAL AND METHOD:
      The study material consisted of two groups of macerated skulls and the relevant
      lateral cephalograms. The first group comprised 32 skulls of individuals aged 2.5
      to 5 years, and the second group ten skulls of individuals aged 18 to 20 years. A
      diagram showing the growth-dependent changes was prepared with reference to the
      mean values for the two groups. The cephalograms were superimposed on the
      anterior cranial base line at sella point (S). RESULTS: A 3.1 degrees increase in
      the angle between FH and SN during growth was recorded in our investigations. The
      distance between Or and SN increased by 3.9 mm while Po remained vertically
      almost constant with respect to SN. In sagittal direction the distance between Or
      and S also increased, while Po was displaced to almost the same extent in the
      opposite direction. The increasing vertical distance between the anterior and
      posterior reference points of FH and SN was largely compensated by the sagittal
      developments of the reference points Po and Or, so that the angle between these
      two planes changed very little. The relatively stable angle between FH and SN
      thus showed by no means a constant relationship of the four reference points to
      one another.

PMID- 15160250
TI  - The influence of intermittent forces during daytime application of the SIII
      appliance.
AB  - Daytime application of the SIII appliance results in mainly intermittent forces.
      Permanent force occurs only for a few minutes, if at all. These intermittent
      forces may be as high as 40 N in individual cases. Depending upon the patient's
      activity and temperament, 10 to more than 100 intermittent force impulses per
      minute can occur. The intermittent forces account for the therapeutic effects
      found in young patients.

PMID- 15160249
TI  - Plasma versus halogen light: the effect of different light sources on the shear
      bond strength of brackets.
AB  - The aim of this study was to investigate differences between plasma and halogen
      light polymerization in relation to the attainable shear bond strength of
      brackets bonded with various adhesives. 720 brackets were divided into 72
      different groups of n = 10. The brackets were bonded to 240 flat polished test
      specimens produced from bovine teeth, Pontor MPF alloy, and extra hard plaster
      (type III) respectively. Transbond XT, Kurasper F or Fuji Ortho LC served as
      adhesives to bond either ceramic (Transcend 6000) or stainless steel brackets
      (Mini Uni-Twin). 50% of all brackets were bonded with a minimum layer of
      adhesive, and the remaining 50% with an adhesive layer thickness of 1.0 mm. In
      360 cases the adhesive was polymerized with a plasma light (PAC), and in a
      further 360 cases with a halogen light (Optilux 401). The light curing time was
      10 s with plasma light and 40 s with halogen light. After 24 h of storage in
      deionized water at room temperature, all brackets were subjected to a shear bond
      strength test according to ISO standard 10477. The measured shear bond strength
      did not differ significantly between the two curing light sources. The 1 mm
      adhesive layer thickness group showed significantly higher shear bond strengths
      in comparison to the minimum layer thickness group.

PMID- 15160251
TI  - Vertical changes in patients with complete unilateral and bilateral cleft lip,
      alveolus and palate.
AB  - AIMS AND METHODS: Twelve UCLP and eleven BCLP patients who had been treated
      according to the Hanover treatment protocol were evaluated by means of
      cephalometric analysis and cast measurements. The aim of this investigation was
      to demonstrate changes in the vertical plane and in incisor position in the
      course of craniofacial growth compared to age-matched non-cleft controls. Lateral
      cephalograms and casts were analyzed for each cleft patient at age 10 and 15 and
      compared with corresponding data of a non-cleft control group (n = 20). RESULTS:
      A vertical growth impairment of the maxilla was registered in patients with cleft
      lip, alveolus and palate. The maxilla of the cleft patients showed a significant
      clockwise rotation while the inclination of the mandible remained virtually
      unchanged. Both upper and lower incisors, which were significantly retruded at
      the beginning of the late mixed dentition, could be protruded in the course of
      craniofacial growth, development of the dentition and treatment, but remained
      retruded in comparison with the non-cleft controls. The posterior midfacial
      height was highly significantly shorter in both UCLP and BCLP patients at both
      evaluation timepoints, whereas the anterior lower jaw height was greater than in
      the control group

PMID- 15160252
TI  - Possibilities and limitations of comprehensive treatment of mentally retarded
      patients with cleft lip, alveolus and palate.
AB  - The comprehensive, successful treatment of patients with cleft lip, alveolus and
      palate requires numerous surgical interventions and very close cooperation
      between various medical and dental specialists. The willingness and ability of
      the patient to undergo treatment are undoubtedly important factors in achieving
      optimal treatment outcomes. The presented case report shows that limited
      compliance makes it much more difficult for speech pathologists and orthodontists
      to treat mentally retarded patients. Only with combined orthodontic therapy and
      orthognathic surgery could the dental and skeletal abnormalities be corrected in
      adulthood.

PMID- 15160253
TI  - Giant-cell tumors of bone: an analysis of 87 cases.
AB  - We reviewed 87 patients with giant-cell tumor treated between 1992 and 2001. The
      mean follow-up was 62 (28-138) months. Fifty-six lesions were treated with
      intralesional curettage with adjunctive phenol treatment and reconstructed with
      autograft and allograft. Thirty-one lesions were treated with wide resection and
      reconstructed with prosthesis, osteochondral allograft, or alloprosthetic
      composite. Overall recurrence was 12%. Recurrence rate after curettage was 18%
      and 3% after wide excision. Complication rate after wide excision was higher than
      that after curettage. Functional outcome was evaluated using the Enneking scoring
      system. Average rating was 86% for the lower extremity and 83% for the upper
      extremity. The overall satisfactory rate was 88%.

PMID- 15160254
TI  - Intramedullary nailing in open tibia fractures: a comparison of two techniques.
AB  - We analyzed 51 patients with open tibial fractures treated with intramedullary
      nailing. In 29 patients the nailing was performed without reaming and in 22 after
      the "reamed-to-fit" technique. There was no statistically significant difference
      in the rate of union. The nonreamed group required a greater number of secondary
      procedures to achieve union and had a higher but not statistically significant
      incidence of infection. Analysis of the operative and anesthesia cost associated
      with the additional procedures revealed that on average, patients receiving
      nonreamed nailing incurred a cost of $4,900 more per fracture than patients of
      the reamed-to-fit technique. The healing rates of open tibia fractures using
      either minimally reamed or nonreamed techniques of intramedullary nailing are
      comparable. No increase in the rate of infection with the reamed-to-fit technique
      was found. A significant increase in the number of secondary procedures required
      to achieve union was found with the nonreamed nailing technique.

PMID- 15160256
TI  - Osteosarcoma associated with hyperparathyroidism.
AB  - The fourth case in the literature is presented of a patient with the rare
      association of hyperparathyroidism and osteosarcoma. A 56-year-old woman
      presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis
      was brown tumor. Histology, however, revealed osteosarcoma, and the patient was
      treated accordingly. The experimental induction of osteosarcoma by parathormone
      in rodent studies makes this finding alarming, considering the increasing use of
      parathormone in the treatment of osteoporosis. The mechanism by which
      osteosarcoma is induced in humans cannot be explained based on current knowledge
      of mechanisms of action of parathyroid hormone.

PMID- 15160255
TI  - Calcifying tendinitis of the rotator cuff with cortical bone erosion.
AB  - Calcifying tendinitis occurs most commonly in the rotator cuff tendons,
      particularly involving the supraspinatus tendon insertion, and is often
      asymptomatic. Cortical erosion secondary to calcifying tendinitis has been
      reported in multiple locations, including in the rotator cuff tendons. We present
      a pathologically proven case of symptomatic calcifying tendinitis involving the
      infraspinatus tendon with cortical erosion with correlative radiographic, CT, and
      MR findings. The importance of considering this diagnosis when evaluating lytic
      lesions of the humerus and the imaging differential diagnosis of calcifying
      tendinitis and cortical erosion are discussed.

PMID- 15160257
TI  - Novel procedures for high-throughput analysis of a frequent insertion-deletion
      polymorphism in the human T-cell receptor beta locus.
AB  - The human T-cell receptor beta locus ( TRB) contains two frequent insertion
      deletion polymorphisms. In one, the insertion comprises two functional variable
      beta genes, TRBV6-2/TRBV6-3 and TRBV4-3, and the pseudogene TRBV3-2. Deletion of
      these TRBV genes may confer resistance and/or susceptibility to autoimmunity,
      analogously to findings in rodent models. Curiously, the TRBV domains in the
      insertion react with the HERV-K18 superantigen associated with type 1 diabetes.
      While this region has been extensively characterized before, typing methods
      compatible with high-throughput analysis are not yet available. Here, two novel
      procedures are reported that are suitable for large-scale association analysis of
      this polymorphism. One features a duplex TaqMan 5'-exonuclease assay that
      quantifies the gene dosage of TRBV3-2 present at 0, 1 or 2 copies, with its
      closely related diploid relative TRBV3-1 as an internal reference, using the 2(
      DeltaDeltaC)(T) method. The other technique consists of two complementary long
      PCRs with primers specific for unique regions in the locus. The first
      discriminates individuals heterozygous or homozygous for the deletion, and the
      second, individuals heterozygous or homozygous for the insertion from other
      genotypes. These simple, solid, and cross-validated procedures can now be used in
      conjunction with flanking single-nucleotide polymorphisms for large-scale linkage
      studies.

PMID- 15160258
TI  - Taurine protects against PMN dysfunction and death in urine.
AB  - The polymorphonuclear neutrophil (PMN) is the primary pro-inflammatory cell in
      the host response to bacterial infection and, as the first line of defence, is
      the principal cell responsible for the recognition, phagocytosis and killing of
      bacteria. PMN function is known to be defective in the urine. High osmolarity is
      physiologic in the urine and this hypertonic environment has been shown to
      compromise neutrophil function. In this study, PMN function was found to be
      suppressed in urine. This correlated with significant cell death, both by
      apoptosis and necrosis. The amino acid taurine down regulated PMN cell death and
      preserved function in the urine, suggesting taurine as a therapeutic option for
      urinary tract infection.

PMID- 15160259
TI  - Diffusion-tensor imaging in septo-optic dysplasia.
AB  - One of the morphological correlates of septo-optic dysplasia is hypoplasia of the
      optic nerves. As of now, it remains unknown, in how far this disorder also
      affects the organization of the optic radiation. Using diffusion-tensor imaging
      (DTI), the non-invasive evaluation of large fiber tracts including the optic
      radiation has become possible. We have compared DTI-data from a patient suffering
      from septo-optic dysplasia with those of a group of eleven healthy control
      subjects. The anisotropy showed statistically significant reduction in the
      patient with septo-optic dysplasia within the visual fiber tracts and an
      unordered eigenvector map. A comparison of the anisotropy in the pyramidal tract
      showed no significant difference. Since the patient was congenitally blind, it
      remains unclear whether the findings are the results of the underlying disorder
      or occur in all congenitally blind patients. One might presume, that, in order
      for the optic radiation to fully develop, an afferent input to the lateral
      geniculate body is necessarry.

PMID- 15160261
TI  - Escitalopram versus citalopram: the surprising role of the R-enantiomer.
AB  - RATIONALE: Citalopram is a racemate consisting of a 1:1 mixture of the R(-)- and
      S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake
      inhibitory activity of citalopram is attributable to the S-enantiomer,
      escitalopram. A series of recent non-clinical and clinical studies comparing
      escitalopram and citalopram to placebo found that equivalent doses of these two
      drugs, i.e. containing the same amount of the S-enantiomer, showed better effect
      for escitalopram. These results suggested that the R-citalopram in citalopram
      inhibits the effect of the S-enantiomer. OBJECTIVE: To review the pharmacological
      and non-clinical literature that describes the inhibition of escitalopram by R
      citalopram, as well as the implications of this inhibition for the clinical
      efficacy of escitalopram compared to citalopram. METHODS: The information in this
      review was gathered from published articles and abstracts. RESULTS: In
      appropriate neurochemical, functional, and behavioural non-clinical experiments,
      escitalopram shows greater efficacy and faster onset of action than comparable
      doses of citalopram. The lower efficacy of citalopram in these studies is
      apparently due to the inhibition of the effect of the S-enantiomer by the R
      enantiomer, possibly via an allosteric interaction with the serotonin
      transporter. Data from randomised clinical trials consistently show better
      efficacy with escitalopram than with citalopram, including higher rates of
      response and remission, and faster time to symptom relief. CONCLUSION: The R
      enantiomer present in citalopram counteracts the activity of the S-enantiomer,
      thereby providing a possible basis for the pharmacological and clinical
      differences observed between citalopram and escitalopram.

PMID- 15160263
TI  - A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic
      effects in human brain: findings from neuroendocrine challenge tests.
AB  - RATIONALE: Perospirone is a new antipsychotic drug in which dopamine D(2)
      antagonist and serotonin 5-HT(2) antagonist effects have been found in animal
      studies. It was developed by a Japanese pharmaceutical company and launched in
      2001. Perospirone's receptor binding profile may resemble that of atypical
      antipsychotic drugs, but to date there has been no evidence relating to its
      receptor binding affinity in the human brain. OBJECTIVE: The purpose of this
      study was to investigate the receptor binding profile of perospirone via
      neuroendocrine challenge tests. METHODS: Twenty subjects (ten females and ten
      males) were tested on four occasions in a double-blind, cross-over design
      receiving: (a) placebo, (b) perospirone 4 mg, (c) paroxetine 20 mg, and (d)
      paroxetine 20 mg plus perospirone 4 mg, administered orally at 8.00 a.m. Plasma
      cortisol and prolactin levels were measured prior to administration and every
      hour for 6 h thereafter. In addition, psychological responses rated by visual
      analog scales and vital signs such as body temperature, pulse, and blood pressure
      were assessed in combination with blood sampling. RESULTS: Perospirone 4 mg
      increased prolactin levels significantly higher than placebo, whereas paroxetine
      20 mg plus perospirone 4 mg significantly attenuated cortisol responses induced
      by paroxetine 20 mg. CONCLUSIONS: The present findings suggest that perospirone
      has the characteristics of both D(2) and 5-HT(2) antagonist in the human brain.
      Further PET studies in the human brain are required in order to directly
      investigate these effects.

PMID- 15160262
TI  - Anxiogenic effect of sleep deprivation in the elevated plus-maze test in mice.
AB  - RATIONALE: Several clinical studies demonstrate that the absence of periods of
      sleep is closely related to occurrence of anxiety symptoms. However, the basis of
      these interactions is poorly understood. Studies performed with animal models of
      sleep deprivation and anxiety would be helpful in the understanding of the
      mechanisms underlying this relationship, but some animal studies have not
      corroborated clinical data, reporting anxiolytic effects of sleep deprivation.
      OBJECTIVES: The aim of the present study was to verify the effects of different
      protocols of sleep deprivation in mice tested in the elevated plus-maze and to
      assess the effect of chlordiazepoxide and clonidine. METHODS: Three-month-old
      male mice were sleep-deprived for 24 or 72 h using the methods of single or
      multiple platforms in water tanks. Mice kept in their home cages were used as
      controls. Plus-maze behavior was observed immediately after the deprivation
      period. RESULTS: Mice that were sleep-deprived for 72 h spent a lower percent
      time in the open arms of the apparatus than control animals. This sleep
      deprivation-induced anxiety-like behavior was unaffected by treatment with
      chlordiazepoxide (5.0 and 7.5 mg/kg IP), but reversed by an administration of 5
      or 10 microg/kg IP clonidine. CONCLUSION: The results indicate that under
      specific methodological conditions sleep deprivation causes an increase in
      anxiety-like behavior in mice exposed to the elevated plus-maze.

PMID- 15160264
TI  - Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor,
      hypnotic, anxiolytic and amnesic effects.
AB  - RATIONALE: Acetaldehyde, the first metabolite of ethanol, was recently suggested
      to contribute to many behavioral effects of ethanol, although few studies have
      directly investigated the behavioral effects of acetaldehyde itself. OBJECTIVES:
      The aim of the present study was to characterize the locomotor, hypnotic,
      anxiolytic-like and amnesic effects of acetaldehyde in C57BL/6J mice. METHODS:
      Increasing doses of acetaldehyde (0-300 mg/kg) were injected intraperitoneally
      and their effects on a series of representative behaviors were investigated. The
      locomotor effects of acetaldehyde were measured in activity boxes. The duration
      of the loss of righting reflex was used as an index of the hypnotic effects of
      acetaldehyde. The anxiolytic-like effects of acetaldehyde were tested with an
      elevated plus-maze and the amnesic effects with the one-trial passive avoidance
      test. Finally, brain and blood acetaldehyde concentrations were assessed.
      RESULTS: Acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and
      higher doses. In addition, the hypnotic effects of acetaldehyde were demonstrated
      by a loss of righting reflex after the administration of 170 and 300 mg/kg
      acetaldehyde. The elevated plus-maze showed that acetaldehyde does not possess
      anxiolytic-like properties. Finally, acetaldehyde (100-300 mg/kg) dose
      dependently altered memory consolidation as shown by a reduced performance in the
      passive avoidance test. CONCLUSIONS: The present results show that acetaldehyde
      induces sedative, hypnotic and amnesic effects, whereas it is devoid of stimulant
      and anxiolytic-like properties in C57BL/6J mice. However, the behavioral effects
      of acetaldehyde after intraperitoneal administration were apparent at very high
      brain concentrations. The present results also indicate that acetaldehyde is
      unlikely to be involved in the anxiolytic properties of ethanol in mice.

PMID- 15160269
TI  - Different methods to determine length heteroplasmy within the mitochondrial
      control region.
AB  - The first and second hypervariable regions of the human mitochondrial DNA control
      region contain two homopolymeric stretches of cytosine (nt 16184-16193 and nt303
      315, respectively). According to the Cambridge reference sequence these
      homopolymeric stretches are interrupted by thymine (T), at positions 16189 and
      310, respectively. Monotonous runs of the same base have been suggested to be hot
      spots for mutations, probably caused by replication slippage, resulting in length
      heteroplasmy. This paper describes a rapid method based on restriction cleavage
      of labelled PCR products encompassing the homopolymeric tract in HVII to quantify
      the relative proportions of different length variants present in an individual.
      To compare the accuracy of this method, cloned PCR products from several
      heteroplasmic individuals have been additionally sequenced.

PMID- 15160265
TI  - Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive
      aggression.
AB  - RATIONALE: Impulsive aggressive personality disordered patients have been shown
      to have decreased relative glucose metabolism in orbito-frontal cortex and
      anterior cingulate gyrus compared with normal subjects. In addition, patients
      with impulsive aggression have an attenuation of symptoms with selective
      serotonin reuptake inhibitor (SSRI) treatment. OBJECTIVES: The goals of the
      present study were to attempt to replicate the finding of improvement in
      impulsive aggression in borderline personality disorder with SSRIs and to
      investigate the specific cortical areas modified by medication, which might
      underlie the observed clinical improvement using (18)FDG-PET. METHODS: Ten
      impulsive aggressive patients with borderline personality disorder were imaged
      with (18)F-deoxyglucose positron emission tomography at baseline and after
      receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered
      to PET and relative metabolic rates were obtained in 39 Brodmann areas. RESULTS:
      Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant
      increases in relative metabolic rate. Significant clinical improvement was also
      observed as assessed by the Overt Aggression Scale-Modified. CONCLUSIONS: These
      changes are consistent with a normalizing effect of fluoxetine on prefrontal
      cortex metabolism in impulsive aggressive disorder.

PMID- 15160270
TI  - Lessons from ALLHAT. Are low budget diuretics first line therapy in hypertension?
AB  - Diuretics are well-established and nowadays also cheap cardiovascular agents. In
      contrast to the most recent American hypertension guidelines (JNC 7) which
      ascribe a singular place to diuretics in the first-line treatment of hypertension
      following a one-sided interpretation of the ALLHAT results, in the balanced
      guidelines of the European Society of Hypertension (ESH) published in 2003, they
      are placed alongside beta-blockers, ACE inhibitors, sartans and calcium
      antagonists as the drugs of first choice, but not given preference. Previous
      scientific evidence and clinical experience is to a certain extent in line with
      this classification of diuretics. On the basis of the indisputable dose-dependent
      potential for side-effects such as hypokalaemia, diabetogenicity and stimulation
      of neurohumoural systems, I personally consider diuretics to be inferior to the
      more recent substance groups, particularly the RAS inhibitors. I would therefore
      welcome it if diuretics in the future were removed from the monotherapy of
      hypertension and offered from the outset as low-dosed combination partners for
      RAS inhibitors, beta-blockers and also calcium antagonists. In this role they
      could only do good and not cause any damage.

PMID- 15160271
TI  - [The stakes of force perseverance training and muscle structure training in
      rehabilitation. Recommendations of the German Federation for Prevention and
      Rehabilitation of Heart-Circulatory Diseases e.v].
AB  - While aerobic endurance training has been a substantial part of international
      recommendations for cardiac rehabilitation during the last 30 years, there is
      still a rather reserved attitude of the medical community to resistance exercise
      in this field. Careful recommendations for resistance exercise in cardiac
      patients was only published a few years ago. It has been taken for granted that
      strength exercise elicits a substantial increase in blood pressure and thus
      imposes, especially in cardiac patients, a risk of potentially fatal
      cardiovascular complications. Results of the latest studies show that the
      existing recommended overcaution is not justified. Strength exercise can indeed
      result in extreme increases of blood pressure, but this is not the case for all
      loads of this kind. The actual blood pressure response to strength exercise
      depends on the isometric component, the exercise intensity (load or resistance
      used), muscle mass activated, the number of repetitions in the set and/or the
      duration of the contraction as well as involvement of Valsalva maneuver. Intra
      arterially performed blood pressure measurements during resistance exercise in
      patients with heart disease showed that strength training carried out at low
      intensities (40-60% of MVC) and with high numbers of repetitions (15-20) only
      evokes a moderate increase of blood pressure comparable with blood pressure
      measures induced by moderate endurance training. If used properly and performed
      accurately, individually dosed, medically supervised and controlled through
      experienced sport therapists, a dynamic resistance exercise is-at least for a
      certain group of patients-not associated with higher risks than an aerobic
      endurance training and can in addition to endurance training improve muscle force
      and endurance, have a positive influence on cardiovascular function, metabolism,
      cardiovascular risk factors as well as psychosocial well-being and overall
      quality of life. However, with respect to currently available data, resistance
      exercise cannot be generally recommended for all groups of patients. The
      appropriate kind and execution of training is highly dependent on current
      clinical status, cardiac capacity as well as possible accompanying diseases of
      the patient. Most of the studies carried out up to date included small samples of
      middle-aged male patients with almost normal levels of aerobic endurance
      performance and good left ventricular function. Data is missing for risk groups,
      older patients and women. Therefore, an integration of dynamic resistance
      exercises in cardiac rehabilitation can only be recommended without hesitation
      for CHD patients with high physical capacity (good myocardial function,
      revascularized). Since patients with myocardial ischemia and/or low left
      ventricular functioning might develop wall motion disturbances and/or dangerous
      ventricular arrhythmia when performing resistance exercises, prevalence of the
      following conditions is recommend: moderate to high LV-function, high physical
      performance (>5-6 metabolic equivalents= >1.4 watts/kg body weight) in absence of
      angina pectoris symptoms or ST-depression, by maintained current medication. In
      the proposed recommendations, a classification of risks for resistance training
      in cardiac rehabilitation is being made based on current data and is complemented
      by specific recommendations for particular groups of patients and detailed
      guidelines for setup and completion of the therapy program.

PMID- 15160272
TI  - Postoperative junctional ectopic tachycardia (JET).
AB  - Postoperative junctional ectopic tachycardia (JET) is a potential life
      threatening tachycardia that mainly occurs after surgical correction of
      congenital heart defects. The arrhythmia itself or the related treatment has
      significant clinical impact on the postoperative course and intensive care stay.
      In general, JET is a self-limiting disorder that usually resolves within one
      week. However, JET occurs usually within the first 24 to 48 hours after
      corrective surgery, when systolic and diastolic function of the heart is
      impaired. Thus, the rapid heart rate leads to an acute further deterioration of
      cardiac output that requires adequate treatment. The diagnosis of JET is made by
      the typical ECG-appearance with narrow QRS-configuration at a rate of 170 to 260
      bpm and AV-dissociation. A variety of different therapeutic strategies have been
      tested in postoperative and congenital/spontaneous JET. Treatment success is
      usually defined as a stable decrease in the ventricular rate below 140-150/min,
      the possibility of atrial pacing and thereby the improvement of cardiac output.
      Optimal success is the reinstitution of sinus rhythm. Many of the treatment
      strategies reported are based on specific institutional treatment protocols.
      These include conventional supportive treatment, specific medical antiarrhythmic
      therapy, specific forms of pacing and surface cooling. Today, the administration
      of high doses of amiodarone usually leads to adequate control of the rate and
      enables pacing. Surgical intervention or catheter ablation of the HIS-bundle is
      rarely necessary. This article reviews the literature about JET over the past
      years and offers a specific treatment protocol.

PMID- 15160273
TI  - [Ambulatory electrocardioversion of atrial fibrillation by means of biphasic
      versus monophasic shock delivery. A prospective randomized study].
AB  - Transthoracic electrical cardioversion using a monophasic waveform is the most
      common method converting persistent atrial fibrillation into sinus rhythm.
      Recently, cardioversion with a new biphasic waveform has shown promising results
      for treatment of atrial fibrillation. We undertook a randomized prospective trial
      comparing the efficacy and safety of the two waveforms for ambulatory
      cardioversion of atrial fibrillation. A total of 118 consecutive patients (mean
      age 62 years [SD 11]) presenting with persistent atrial fibrillation (mean
      duration 8 months [SD 11]) for ambulatory electrical cardioversion were
      randomized to receive either monophasic (n = 57) or biphasic shocks (n = 61). We
      used a standardized step-up protocol with increasing shock energies (100-360
      joules) in either group. In all patients an anterior-posterior shock electrode
      position was used. If sinus rhythm was not achieved with the third (360 joules)
      shock, cardioversion was repeated with the opposite waveform. The two groups did
      not differ in demographic or disease-related data. The success rate was 100% for
      the biphasic and 73.7% for the monophasic waveform (p < 0.001). Biphasic patients
      required fewer shocks (1.5 versus 2.9) and a lower mean cumulative energy (203
      versus 570 joules) (p < 0.001). Twelve out of 15 unsuccessfully treated
      monophasic patients were converted with biphasic shocks. The success rate for all
      118 patients was 97.5%. No major acute complications were observed. For
      ambulatory transthoracic cardioversion of persistent atrial fibrillation biphasic
      shocks are of greater efficacy and require less energy than monophasic shocks.
      The procedure can be performed ambulatory and is safe regardless of shock
      waveform used.

PMID- 15160274
TI  - A superior early myocardial infarction marker. Human heart-type fatty acid
      binding protein.
AB  - Human heart-type fatty acid-binding protein (FABP) has a high potential as an
      early marker for myocardial infarction (MI) being more specific than myoglobin.
      FABP is a low molecular mass cytoplasmic protein (15 kDa) that is released early
      after the onset of ischemia and it may be useful for rapid confirmation or
      exclusion of acute myocardial infarction (AMI). Immunochemically assayed FABP,
      cardiac troponin I (cTnI) and enzymatically assayed creatine phosphokinase (CPK)
      were determined serially in plasma and serum samples from 218 patients presenting
      with chest pain and suspected MI. In the 94 patients with confirmed MI, FABP rose
      to a maximum level (577.6 +/- 43.8 microg/L) 3 hours after the onset of symptoms
      and returned to normal within 30 hours. The FABP level peaked 7-9 hours earlier
      than CPK (2288 +/- 131 U/L) and cTnI (357.1 +/- 23.9 microg/L). CPK took 50-70
      hours to return to normal level and cTnI returned to normal level over 70 hours.
      The areas under the receiver operating characteristic (ROC) curves for FABP were
      calculated as 0.871 at admission and 0.995 one hour after admission, whereas for
      CPK the areas were 0.711 and 0.856 and for cTnI the areas were 0.677 and 0.845,
      indicating that the FABP test gave a better diagnostic classification at the
      early stage being reached by cTnI (0.995) only 8 hours after admission. For FABP,
      both sensitivity and negative predictive value (NPV) increased quickly to 100%
      for samples monitored just one hour after admission. By using only two samples,
      one at admission and one 1 hour post admission, sequential FABP monitoring can
      reliably diagnose AMI patients 1 hour after admission and 100% of non-AMI
      patients can be excluded with no false negative results. The late markers cTnI
      and CPK have the similar diagnostic performance only 7 hours later. Thus
      measurement of FABP in plasma or serum allows the earliest immunochemical
      confirmation or exclusion of AMI.

PMID- 15160275
TI  - Class-specific pro-apoptotic effect of statins on human vascular endothelial
      cells.
AB  - Neonangiogenesis represents an important step in tumor development and
      propagation. Statins may have anticancerogenic potential by blocking vascular
      endothelial cell growth. The antiproliferative effect of four statins on human
      endothelial cells was compared, concomitantly delineating a possible pro
      apoptotic process. All four statins tested, i. e. atorvastatin, fluvastatin,
      lovastatin, and simvastatin inhibited cell proliferation. Nearly complete
      blocking of cell proliferation was achieved at a concentration of 10 microM. We
      were able to demonstrate that the antiproliferative effect of the statins is not
      due to cytotoxicity but rather to an apoptotic effect as demonstrated by
      comparison of cytotoxicity assay and apoptosis assay. The apoptotic mechanism
      seems to involve caspases, since the statins significantly enhanced caspase
      activity at dosages of 10 and 20 microM. Further experiments revealed a
      downregulation of the pro-apoptotic protein Bcl-2. Our data indicate that statins
      may class-specific inhibit angiogenesis at high dosages which can contribute to
      prevention of tumor development and progression.

PMID- 15160276
TI  - [Platypnea-orthodeoxia of a 69-year old woman with a patent foramen ovale].
AB  - Platypnea-orthodeoxia is a rare syndrome that is often associated with
      interatrial shunting through a patent foramen ovale (PFO) or atrial septal
      defect. We describe the case of a 69-year-old woman with progressive dyspnea and
      hypoxia when standing, which was relieved by assuming the recumbent position.
      After detection of a PFO by transesophageal echocardiography the diagnosis was
      confirmed by transthoracic echocardiography using saline contrast injection while
      lying supine and standing upright. This maneuver demonstrated a large right-to
      left shunt through a patent foramen ovale while the patient was in a upright
      position and no significant shunt while being in a recumbent position. The
      patient showed a rapid improvement after closure of the PFO. This case
      demonstrates that platypnea-orthodeoxia caused by a patent foramen ovale can be
      easily demonstrated by the technique of contrast transthoracic echocardiography
      and a simple positioning maneuver.

PMID- 15160277
TI  - Successful recanalization of an occluded coronary artery by percutaneous coronary
      intervention, systemic administration of tirofiban, a glycoprotein IIb/IIIa
      inhibitor, and intracoronary thrombolysis with alteplase.
AB  - A 51 year-old male was admitted to our institution with subacute inferior
      myocardial infarction. Coronary angiography showed thrombotic occlusion of the
      right coronary artery. Percutaneous coronary intervention including the delivery
      of 3 stents was unsuccessful (TIMI grade 0 flow). In addition to an ongoing
      systemic administration of tirofiban, a glycoprotein IIb/IIIa inhibitor, the
      patient received intracoronary thrombolysis (ICT) with alteplase (recombinant
      tissue type plasminogen activator, rt-PA). There was complete reperfusion on
      control angiography the following day (TIMI grade 3 flow); 7 months later, there
      was still TIMI grade 3 flow. To our knowledge, this is the first report on
      systemic administration of tirofiban combined with ICT.

PMID- 15160278
TI  - Calculation of individual cardiovascular risk in a primary prevention setting
      shows a high number of patients with a high risk score.
AB  - On occasion of the annual convention of the European Society of Cardiology,
      general awareness was used to stage an event to inform the public about
      cardiovascular risk and cardiovascular disease. After the measurement of blood
      pressure, HDL and total cholesterol and after answering questions on smoking and
      medication visitors received a printout showing their individual calculated
      cardiovascular event rate over the next ten years. For the calculation of the
      expected event rate, the algorithm of the Adult Treatment Panel III was used. Of
      the 43,500 visitors 1513 were screened, 651 male, 862 female. Of those screened
      in this primary prevention setting 143 male (22.07%) and 9 female (1.02%) had an
      expected cardiovascular event rate of 20% or more over the next ten years
      requiring immediate action according to the current guidelines. The calculated
      risk scores are considerably lower than would be expected in a representative
      sample from the population. This indicates that patients with a high
      cardiovascular risk possibly do not take part in unstructured primary screening
      events.

PMID- 15160279
TI  - [Position paper on the use of drug eluting stents in coronary heart disease].

PMID- 15160283
TI  - Cryopreservation of embryogenic suspension cultures of Cyclamen persicum mill.
AB  - We have developed a simple protocol for the cryopreservation of embryogenic
      suspension cultures of Cyclamen persicum. Embryogenic suspension cultures in the
      linear growth phase 7-10 days after subculture were used for cryopreservation. Of
      the different cryoprotectants tested during a 2-day pre-culture, 0.6 M sucrose
      resulted in the highest re-growth rates of 75%. An additional pre-treatment with
      0.6 M sucrose and 10% DMSO (dimethylsulfoxide) for 1 h also positively affected
      re-growth. Microscopic studies on viability revealed that only few small
      embryogenic cells survived cryopreservation, while vacuolated single cells died.
      Experiments in which the duration of the pre-culture period--i.e. the length of
      time the embryogenic suspension cells were exposed to 0.6 M sucrose--was varied
      showed that 2-4 days was the most optimal exposure time to 0.6 M sucrose. Callus
      re-grown after cryopreservation showed growth rates similar to that of unfrozen
      callus and regenerated even higher numbers of somatic embryos than unfrozen
      callus.

PMID- 15160282
TI  - Venom effects on monoaminergic systems.
AB  - The monoamines, dopamine, epinephrine, histamine, norepinephrine, octopamine,
      serotonin and tyramine serve many functions in animals. Many different venoms
      have evolved to manipulate monoaminergic systems via a variety of cellular
      mechanisms, for both offensive and defensive purposes. One common function of
      monoamines present in venoms is to produce pain. Some monoamines in venoms cause
      immobilizing hyperexcitation which precedes venom-induced paralysis or
      hypokinesia. A common function of venom components that affect monoaminergic
      systems is to facilitate distribution of other venom components by causing
      vasodilation at the site of injection or by increasing heart rate. Venoms of some
      scorpions, spiders, fish and jellyfish contain adrenergic agonists or cause
      massive release of catecholamines with serious effects on the cardiovascular
      system, including increased heart rate. Other venom components act as agonists,
      antagonists or modulators at monoaminergic receptors, or affect release, reuptake
      or synthesis of monoamines. Most arthropod venoms have insect targets, yet,
      little attention has been paid to possible effects of these venoms on
      monoaminergic systems in insects. Further research into this area may reveal
      novel effects of venom components on monoaminergic systems at the cellular,
      systems and behavioral levels.

PMID- 15160284
TI  - Pharmacokinetic linearity of i.v. vinorelbine from an intra-patient dose
      escalation study design.
AB  - As pharmacokinetics represents a bridge between pharmacological concentrations
      and clinical regimens, the pharmacokinetic exploration of the therapeutic dose
      range is a major outcome. This study was aimed at assessing pharmacokinetic
      linearity of i.v. vinorelbine through an open design with intra-patient dose
      escalation (3 doses/group). Three groups of six patients received either 20-25-30
      mg/m2; or 25-30-35 mg/m2; or 30-35-40 mg/m2. The inclusion criteria were:
      histologically confirmed tumour with at least one assessable target lesion, age
      25-75 years, WHO PS < or =2, normal haematology and biochemistry, life expectancy
      > or =3 months. The pharmacokinetics was evaluated in both whole blood and plasma
      over 120 h. Twenty-six patients were recruited and 18 were evaluable for
      pharmacokinetics. The toxicity consisted in grade < or =3 leucopenia and
      neutropenia (<20% of courses) and two grade 4 constipation with rapid recovery
      (2/54 courses). Compared to blood, plasma was demonstrated to underestimate the
      pharmacokinetic parameters. In blood, the drug total clearance was about 0.6
      l/h/kg, with minor contribution of renal clearance, steady state volume of
      distribution close to 13 l/h/kg, and elimination half-life at about 40 h. A
      pharmacokinetic linearity was demonstrated up to 40 mg/m2, and even up to 45
      mg/m2 when pooling data from another study. A pharmacokinetic-pharmacodynamic
      relationship was evidenced on leucopenia and neutropenia when pooling the data
      from the two studies.

PMID- 15160285
TI  - Single-dose daily administration of cyclosporin A for relapsing nephrotic
      syndrome.
AB  - Cyclosporin A (CsA) has been reported to be effective as a steroid-sparing agent
      in frequently relapsing nephrotic syndrome (FRNS). However, low efficacy has
      sometimes been observed in selected patients with steroid-dependent FRNS. We
      speculated that a low peak level of CsA in the blood might be the cause, and
      conducted a prospective pilot study on such steroid-dependent FRNS patients to
      examine whether single-dose daily administration of CsA would yield a sufficient
      peak blood level, and therefore a satisfactory steroid-sparing effect. Five
      children with steroid-dependent FRNS, aged 7-16 years, were enrolled in the
      study. All had been treated with prednisolone combined with twice daily CsA ( T),
      which was subsequently replaced with the single-dose daily administration
      protocol ( S), because of a poor steroid-sparing effect. Although the mean daily
      CsA dosage with the S protocol was significantly lower than with the T protocol (
      S 2.4+/-1.1 mg/kg per day vs. T 3.6+/-0.8 mg/kg per day, P<0.05), the mean peak
      blood level tended to be higher with the S protocol than the T protocol ( S 764+/
      122 ng/ml vs. T 358+/-250 ng/ml, P=0.1797) without mean trough blood level
      elevation. As a result, the minimum dose of prednisolone required for maintenance
      of clinical remission tended to be lower with the S than the T protocol ( S 0.4+/
      0.2 mg/kg on alternate days vs. T 0.6+/-0.4 mg/kg on alternate days, P=0.0656).
      No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed
      9 months after commencement of the S protocol in one patient. These clinical
      observations, although on a small number of patients and preliminary, suggest
      that single-dose daily administration of CsA might be an attractive protocol in
      selected patients with steroid-dependent FRNS in whom CsA administration by the
      conventional protocol is associated with a poor steroid-sparing effect.

PMID- 15160287
TI  - Tegumental surface changes in adult Fasciola hepatica following treatment in
      vitro and in vivo with an experimental fasciolicide.
AB  - Our objective was to determine by scanning electron microscopy the structural
      changes in the tegument of adult Fasciola hepatica after treatment with 5-chloro
      2-methylthio-6-(1-naphtyloxy)-1 H-benzimidazole, called compound alpha, and its
      active metabolite sulphoxide, under in vitro and in vivo conditions. For the in
      vitro studies, flukes from sheep were exposed to 40 mg/l of compound alpha
      sulphoxide over different incubation times. Flukes for the in vivo studies were
      raised in sheep treated orally with compound alpha and killed at different times
      post-treatment. Non-treated controls were included for each time of incubation.
      The results showed lesions after 6 h of treatment, such as swelling and furrows.
      At 12 h, the spines appeared to be surrounded by the tegument. At 24 h the
      tegument in some areas showed an exposed basal lamina. These changes became more
      severe as the incubation periods of the treated flukes increased. Compound alpha
      exerts a significant effect on the tegument of F. hepatica.

PMID- 15160288
TI  - Influence of telomerase activity on bone and soft tissue tumors.
AB  - PURPOSE: Telomeres consisting of a repeating nucleotide sequence (TTAGGG)n are
      shortened in normal somatic cells. Telomerase is an enzyme that elongates the
      telomere sequence and is detected in most human cancers and usually not in normal
      somatic cells. Little is known about telomerase activity in bone and soft tissue
      tumors. The aim of this study was to investigate the relationship between
      telomerase activity and clinical factors in bone and soft tissue tumors. METHODS:
      Telomerase activity was measured using the modified telomeric repeat
      amplification protocol (TRAP) assay in 115 bone and soft tissue tumors obtained
      through open biopsy or resection. RESULTS: Telomerase activity was detected in
      10% of benign tumors and 44% of malignant tumors (p < 0.001). A higher incidence
      of telomerase activity was detected in high-grade tumors than in low-grade tumors
      (p = 0.002). The cumulative metastasis-free and overall survival in telomerase
      positive patients was significantly worse than in telomerase-negative patients (p
      = 0.045 and p = 0.048). CONCLUSION: Our study suggests that telomerase activity
      is associated with tumor aggressiveness and may be a useful parameter to predict
      the prognosis of patients with malignant bone and soft tissue tumors.

PMID- 15160290
TI  - Clinical evaluation of in vitro chemosensitivity testing: the example of uveal
      melanoma.
AB  - PURPOSE: Results from in vitro chemosensitivity testing recommend
      treosulfan/gemcitabine chemotherapy for the treatment of stage IV uveal melanoma.
      METHODS: Twenty patients received treosulfan 3,500 mg/m2 followed by gemcitabine
      1,000 mg/m2 on day 1 and day 8 repeated on day 29. In cases of prior chemotherapy
      only 75% of these dosages were used. RESULTS: Without any patient achieving an
      objective response, 25% of patients (95% confidence interval, 8.6-49.1%) had
      stabilisation of disease. This stabilisation was associated with a prolonged
      median overall survival of 17 months compared with 7 months for the patients with
      progressive disease. First-line treatment was not associated with better response
      or survival although prognostic parameters did not significantly differ from that
      of other patients. CONCLUSIONS: The results are disappointing and question the
      value of individualized chemotherapy based on in vitro assays.

PMID- 15160289
TI  - Saccharic acid 1.4-lactone protects against CPT-11-induced mucosa damage in rats.
AB  - PURPOSE: To evaluate the ability of D-saccharic acid 1.4-lactone (SAL), a beta
      glucuronidase inhibitor, to prevent irinotecan hydrochloride (CPT-11) from
      inducing mucosal damage as a cause of diarrhea in rats. METHODS: Wistar rats were
      divided into six groups of three animals each, administered 1.0 ml isotonic
      solution intraperitoneally once daily for up to three consecutive days,
      respectively for up to six days. The series were as follows: (1) On days 1-3:
      saline; (2) On days 1-3: 200 mg CPT-11/m2; (3) On days -3 to -1 relative to the
      first administration of CPT-11: 10 mg/ml SAL; on days 1-3: 200 mg CPT-11/m2; (4)
      On days -3 to +3 relative to the first administration of CPT-11: 10 mg/ml SAL,
      and on days 1-3: additional 200 mg CPT-11/m2; (5) On days 1-3: 200 mg CPT-11/m2
      (0.5 ml) + 10 mg/0.5 ml SAL; (6) On days -3 to -1 relative to the first
      administration of CPT-11: 3 mg/ml SAL, and on days 1-3: 200 mg CPT-11/m2. Luminal
      mucosa damage of the small intestine was detected by histology 24 h after the
      last intraperitoneal application. Peptidase activities of the proximal jejunum
      were measured by using an in situ perfusion model. RESULTS: Following
      intraperitoneal CPT-11 treatment, using conventional histology of paraffin
      sections, we observed severe mucosal damage. This was reflected by a decrease of
      the villi/crypt ratio, an increase of apoptotic cells, as well as an increase of
      mitotic figures in the crypt region. There was a concomitant increased lymphatic
      infiltration in mucosa of CPT-11 treated rats. This damage pattern could be
      clearly reduced by co-treatment with the beta-glucuronidase inhibitor, SAL,
      independent of the treatment schedule. In contrast to our expectations based on
      previous reports, the intraperitoneal application of CPT-11 alone or in
      combination with SAL did not cause significant differences in luminal enzyme
      liberation in comparison with controls in the in situ perfusion assay.
      CONCLUSIONS: The beta-glucuronidase inhibitor SAL is able to significantly reduce
      CPT-11-induced mucosal damage in the small intestine of rats. This observation
      might soon have a clinical impact for the treatment of patients with CPT-11.

PMID- 15160292
TI  - Bromocriptine treatment of prolactinoma restores growth hormone secretion and
      causes catch-up growth in a prepubertal child.
AB  - A 13-year-old Japanese boy with pituitary prolactinoma whose growth had been
      retarded for more than 2 years was treated with bromocriptine alone for 140
      weeks. After treatment, the serum level of prolactin, which was 1200 ng/ml before
      treatment, returned to normal and the pituitary tumour seen on the initial brain
      MRI had rapidly decreased in size after 16 weeks of treatment. Thereafter, his
      height improved (from -2.1 to -1.7 SDS). CONCLUSION: the favourable response
      obtained in this patient implies that bromocriptine monotherapy can be an
      effective first-line treatment for children with prolactinoma.

PMID- 15160291
TI  - Perceived health status in a Turkish adolescent sample: risk and protective
      factors.
AB  - The objective of this study was to investigate health status of Turkish
      adolescents and to determine the factors affecting their self perceptions of
      health. The subjects of the study were 4,153 grade 9-11 students from 26 randomly
      selected high schools in Istanbul. In total, 78% (n = 3231) and 62% (n = 2537) of
      the students reported that they were feeling healthy and happy, respectively.
      Prevalence of headache, abdominal pain and backache; feeling low, irritable,
      nervous and dizzy; medication use for headache, abdominal pain and nervousness
      were higher in females than in males (P < 0.05 for each comparison). Prevalence
      of difficulty in getting to sleep and medication use for it were quite similar in
      both genders. Perceived higher socio-economic status, feeling happy and
      exercising longer than 2-3 h a week were found as protective factors related to
      feeling healthy for both genders. In females, ease of talking to mother and
      perceived adequate parental support on school matters and in males, ease of
      talking to father and satisfaction with body size were protective factors related
      to feeling healthy, respectively. Cigarette smoking and having headaches put
      feeling healthy at risk in both genders. In females, feeling left out of things,
      having backache and dizziness and medication use for nervousness and in males,
      feeling pressured by school work, abdominal pain and difficulty in getting to
      sleep were risk factors related to feeling healthy, respectively. CONCLUSION: the
      findings of this study suggest that a significant number of Turkish adolescents
      perceive themselves as not very healthy and experience psychosomatic symptoms.
      Perception of health differed to some extent according to gender. Programmes
      promoting health-related activities and coping strategies with parental
      participation need to be developed for improving health in high school students.

PMID- 15160294
TI  - Sequence learning and sequential effects.
AB  - In a serial reaction time (RT) task with a probabilistic stimulus sequence, the
      length of the response-to-stimulus interval (RSI) and the sequence complexity was
      manipulated to investigate the relationship between sequence learning and
      sequential effects in serial RT tasks. Sequential effects refer to the influence
      of previous stimulus presentations on the RT to the current stimulus. Sequence
      learning is stimulus-transition specific and is demonstrated as the difference
      between practiced and unpracticed sequences within an interpolated random block
      of trials. There is a clear parallel between sequence learning and specific
      changes in sequential effect in the short RSI conditions, suggesting that a
      common mechanism may lie at the basis of sequence learning and automatic
      facilitation, which is responsible for sequential effects at short RSI.
      Importantly, the changes in sequential effects accompanying sequence learning are
      the same as those observed with practice in random serial RT tasks, indicating
      that the learning process underlying sequence learning is the same as in random
      tasks.

PMID- 15160295
TI  - ECG-gated 23Na-MRI of the human heart using a 3D-radial projection technique with
      ultra-short echo times.
AB  - Pathological changes in tissue often manifest themselves in an altered sodium
      gradient between intra- and extracellular space due to a malfunctioning Na+-K+
      pump, resulting in an increase in total sodium concentration in ischaemic
      regions. Therefore, 23Na-MRI has the potential to non-invasively differentiate
      viable from non-viable tissue by detecting concentration changes of intra- and
      extracellular sodium. As the in vivo sodium signal shows a bi-exponential T2
      decay, with a short component of less than 1 ms, the accurate quantification of
      the total sodium content requires imaging techniques with ultra-short echo times
      (TE) below 0.5 ms. A 3D-radial projection technique has been developed which
      allows the acquisition of ECG-triggered sodium images of the human heart with a
      TE of 0.4 ms. With this pulse sequence 23Na-MRI volunteer measurements of the
      head or the heart were performed in less than 18 min on a 1.5-T clinical scanner
      with an isotropic resolution of 10 mm3. The signal to noise ratio of the radial
      projection technique is twofold higher than that of a Cartesian gradient echo
      pulse sequence (TE = 3.2 ms). Radial 23Na-MRI provides a tool for clinical
      studies, aiming at the differentiation of viable and non-viable tissue.

PMID- 15160296
TI  - Transmit/receive headcoil for optimal 1H MR spectroscopy of the brain in
      paediatric patients at 3T.
AB  - (1)H magnetic resonance (MR) spectroscopy is a useful tool to obtain metabolic
      information from the brain in paediatric patients. To detect signals of
      metabolites at low concentrations or from small volumes, the signal-to-noise
      ratio (SNR) has to be optimized. The SNR can be increased by going to higher
      field strengths. However, this leads to higher spectral bandwidths, which
      increases the chemical shift artefact. Here we present a transmit/receive
      headcoil which is adapted to the dimensions of the paediatric head and enables
      PRESS localization with high radio-frequency (RF) bandwidths that minimize the
      chemical shift displacement to only 5%. In addition, since the pulse lengths are
      shorter with higher RF bandwidths, the echo time can be reduced to 10 ms
      improving SNR as well.

PMID- 15160298
TI  - Glycopeptide resistance in Staphylococcus aureus: is it a real threat?
AB  - Following the discovery in 1992 that resistance to vancomycin could be
      transferred in vitro from a strain of Staphylococcus haemolyticus to
      Staphylococcus aureus, the threat that a similar event could happen in vivo has
      existed. In 1996, the threat became a reality in Japan followed by reports of low
      level heteroresistant S. aureus from elsewhere in the world. However, the threat
      has not gone away; indeed it has become more intimidating within the past 2 years
      with the isolation of higher-level resistance to vancomycin transferred on a
      plasmid from Enterococcus faecalis. The mechanisms of resistance are different in
      each of the types of S. aureus with reduced susceptibility to the glycopeptides:
      in one hetero-vancomycin intermediate-susceptible S. aureus (hVISA) and
      vancomycin intermediate-susceptible S. aureus (VISA), cell wall biosynthesis is
      altered, hindering glycopeptide reaching its target, and in the other vancomycin
      resistant S. aureus (VRSA) the target is altered. This review attempts to place
      into context the threat posed to patients by the appearance of strains of S.
      aureus more resistant to one of the key therapeutic agents used in our hospitals.
      It will do so by raising a number of important questions followed by the
      presentation of experimental evidence that may or may not provide answers that
      heighten or lower the threat.

PMID- 15160297
TI  - Purification and biochemical properties of a thermostable xylose-tolerant beta- D
      xylosidase from Scytalidium thermophilum.
AB  - The thermophilic fungus Scytalidium thermophilum produced large amounts of
      periplasmic beta- D-xylosidase activity when grown on xylan as carbon source. The
      presence of glucose in the fresh culture medium drastically reduced the level of
      beta- D-xylosidase activity, while cycloheximide prevented induction of the
      enzyme by xylan. The mycelial beta-xylosidase induced by xylan was purified using
      a procedure that included heating at 50 degrees C, ammonium sulfate fractioning
      (30-75%), and chromatography on Sephadex G-100 and DEAE-Sephadex A-50. The
      purified beta- D-xylosidase is a monomer with an estimated molecular mass of 45
      kDa (SDS-PAGE) or 38 kDa (gel filtration). The enzyme is a neutral protein (pI
      7.1), with a carbohydrate content of 12% and optima of temperature and pH of 60
      degrees C and 5.0, respectively. beta- D-Xylosidase activity is strongly
      stimulated and protected against heat inactivation by calcium ions. In the
      absence of substrate, the enzyme is stable for 1 h at 60 degrees C and has half
      lives of 11 and 30 min at 65 degrees C in the absence or presence of calcium,
      respectively. The purified beta- D-xylosidase hydrolyzed p-nitrophenol-beta- D
      xylopyranoside and p-nitrophenol-beta- D-glucopyranoside, exhibiting apparent
      K(m) and V(max) values of 1.3 mM, 88 micromol min(-1) protein(-1) and 0.5 mM, 20
      micromol min(-1) protein(-1), respectively. The purified enzyme hydrolyzed
      xylobiose, xylotriose, and xylotetraose, and is therefore a true beta- D
      xylosidase. Enzyme activity was completely insensitive to xylose, which inhibits
      most beta-xylosidases, at concentrations up to 200 mM. Its thermal stability and
      high xylose tolerance qualify this enzyme for industrial applications. The high
      tolerance of S. thermophilum beta-xylosidase to xylose inhibition is a positive
      characteristic that distinguishes this enzyme from all others described in the
      literature.

PMID- 15160299
TI  - Optimization of dose and dose regimen of biapenem based on pharmacokinetic and
      pharmacodynamic analysis.
AB  - Pharmacokinetic and pharmacodynamic (PK/PD) parameters, which are important
      indices of the therapeutic efficacy of antimicrobials, and the minimum inhibitory
      concentration (MIC) predictive of clinical efficacy at common clinical doses,
      were examined for biapenem (BIPM; 300 mg b.i.d.), imipenem/cilastatin (IPM/CS;
      500 mg/500 mg b.i.d.), meropenem (MEPM; 500 mg b.i.d.), and ceftazidime (CAZ;
      1000 mg b.i.d.), using a mouse model of thigh infection caused by Pseudomonas
      aeruginosa. The PK/PD parameter that most closely correlated with the therapeutic
      efficacy of all these antimicrobials was time above MIC (T > MIC). The values of
      T > MIC predictive of clinical efficacy against P. aeruginosa infection varied
      among antimicrobials and were >/=17%, >/=17%, >/=23%, and >/=33% for BIPM,
      IPM/CS, MEPM, and CAZ, respectively. From these values and the known plasma
      concentrations of the antimicrobials in humans after administration at the common
      clinical doses, the MIC for bacterial strains at which clinical efficacy can be
      expected was estimated to be </=4.4 microg/ml for BIPM, </=6.1 microg/ml for
      IPM/CS, </=2.2 microg/ml for MEPM, and </=13.6 microg/ml for CAZ. These MICs
      nearly coincided with the MIC(80) of the antimicrobials for 104 clinical isolates
      of P. aeruginosa strains. These results indicate that, even at a low dose, of 300
      mg b.i.d., the clinical efficacy of BIPM against P. aeruginosa infection can be
      expected to be comparable to that of IPM/CS, MEPM, and CAZ.

PMID- 15160300
TI  - A comparative evaluation of phenotypic and molecular methods for the detection of
      oxacillin resistance in coagulase-negative staphylococci.
AB  - Detection of oxacillin resistance in coagulase-negative staphylococci (C-NS) by
      phenotypic methods is often difficult. The present study compared the National
      Committee for Clinical Laboratory Standards (NCCLS) revised guidelines of
      phenotypic methods with a mecA-based polymerase chain reaction (PCR) for C-NS.
      Ninety clinical C-NS isolates were tested for oxacillin resistance by disk
      diffusion (1-microg disk), minimum inhibitory concentration (MIC) breakpoint (0.5
      microg/ml) after 24 h, and mecA-based PCR. The sensitivity and specificity of
      disk diffusion was 80% and 93%, and the sensitivity and specificity of the MIC
      breakpoint after 24 h was 84% and 91%, respectively, against PCR as gold
      standard. Eleven strains (7 mecA-positive and 4 mecA-negative) showed discordant
      results between MIC breakpoint after 24 h and PCR. Six of the 7 mecA-positive and
      all 4 mecA-negative discordant strains had inducible oxacillin resistance and
      beta-lactamase hyperproduction, respectively. The present study concludes that
      inducible oxacillin resistance and beta-lactamase hyperproduction are the major
      causes of discordant results between phenotypic methods and mecA-based PCR, and
      need special attention.

PMID- 15160302
TI  - Pharmacokinetic-pharmacodynamic analysis of fluoroquinolones against Bacillus
      anthracis.
AB  - Based on the pharmacokinetic-pharmacodynamic (PK-PD) parameters of ciprofloxacin
      in rhesus monkeys, the efficacies of levofloxacin, sparfloxacin, norfloxacin, and
      tosufloxacin against anthrax in humans were examined. The optimal PK-PD parameter
      for the prophylaxis or treatment of infection with Bacillus anthracis is not
      clearly defined. To evaluate the efficacy of fluoroquinolones against anthrax, PK
      PD parameters and the protein-binding effect of fluoroquinolones are used. B.
      anthracis is very susceptible to fluoroquinolones in vitro, and levofloxacin,
      sparfloxacin, and tosufloxacin may be as effective against anthrax as
      ciprofloxacin by PK-PD analysis. However, additional studies of the in vivo model
      are necessary to define more clearly efficacy against anthrax and the
      pharmacodynamic relationship of fluoroquinolones.

PMID- 15160301
TI  - Potent antibacterial activity of Y-754, a novel benzimidazole compound with
      selective action against Helicobacter pylori.
AB  - Y-754, a novel benzimidazole compound, was investigated for in vitro and in vivo
      antibacterial activity. Unlike amoxicillin, clarithromycin, and metronidazole,
      the compound had no activity against common aerobic and anaerobic bacteria other
      than Helicobacter pylori. The minimum inhibitory concentration of Y-754 against
      H. pylori, at 0.025 microg/ml, was nearly equal to that of amoxicillin and
      clarithromycin. The respective concentrations of Y-754, amoxicillin,
      clarithromycin, and metronidazole required to inhibit 90% of 39 isolates of H.
      pylori were 0.05, 0.39, 6.25, and 25 microg/ml, indicating the potent activity of
      Y-754, including activity against clarithromycin- and metronidazole-resistant
      strains. The anti-H. pylori activity of Y-754 was potent even at pH 5.5 and was
      bactericidal at concentrations of 0.1 microg/ml and above. Exposure of H. pylori
      to Y-754 did not result in the induction of drug-resistant mutation. Oral
      administration (10 mg/kg twice a day for 7 days) to Mongolian gerbils infected
      with strain ATCC 43504 demonstrated that Y-754 was effective in H. pylori
      eradication and that its eradication efficacy increased in line with the progress
      of damage to the gastric mucosa caused by H. pylori infection. Y-754 was also
      efficacious in the treatment of infection by the clarithromycin-resistant strain
      OIT-36. The results obtained lead to the expectation that the new benzimidazole Y
      754 will, in the near future, be used for H. pylori eradication therapy in peptic
      ulcer patients.

PMID- 15160303
TI  - Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft.
AB  - We investigated whether fibrin glue (FG) might be useful as a carrier of amikacin
      (AMK) for prevention of local graft infection. After AMK (4.0 mg)-treated FG (AMK
      FG) polyurethane grafts were implanted subcutaneously in the anterior abdominal
      region of Sprague-Dawley rats, AMK concentrations in tissues surrounding the
      implantation sites were compared over time with concentrations at the same sites
      in rats given an intravenous injection of AMK (4.0 mg). In the injection group,
      AMK concentrations in serum were detectable only for 4 h, whereas AMK released
      from AMK-FG grafts remained detectable over 24 h. Until 4 h after implantation,
      AMK concentrations in tissues near implantation sites were significantly higher
      in the AMK-FG graft group than in the injection group; peak local concentrations
      during that time were 210 times higher for the AMK-FG graft group than for the
      injection group. Areas under the tissue concentration-time curve (AUC) for AMK
      were 171 microg x h/g and 1.35 microg x h/g in the AMK-FG graft and injection
      groups, respectively. FG therefore was considered to control release of AMK and
      to maintain a high AMK concentration in tissues surrounding the implantation
      site. Thus, AMK-FG polyurethane graft delivery may be useful in preventing local
      infection by local delivery of AMK.

PMID- 15160304
TI  - The role of the capsule of the Streptococcus milleri group in its pathogenicity.
AB  - Study of the pathogenicity of encapsulated strains of the Streptococcus milleri
      group (SMG) was performed by examination of the ability to cause subcutaneous
      abscesses in mice and by phagocytosis and phagocytic killing of human
      polymorphonuclear neutrophils (PMNs) against the organisms. All 3 encapsulated
      isolates from patients with pneumonia or lung abscess induced abscesses in the
      mice; however, only 2 of 20 unencapsulated isolates from patients with lung
      abscess or thoracic empyema did so. The 3 encapsulated strains inhibited more
      phagocytosis and phagocytic killing of PMNs than the unencapsulated strains. In
      addition, encapsular material separated from Streptococcus constellatus RZYK001
      also inhibited phagocytosis and phagocytic killing in proportion to increasing
      concentrations of the capsular material. These results suggest that capsular
      material produced by SMG might be a pathogenic factor.

PMID- 15160305
TI  - Plasma hepatocyte growth factor is increased in early-phase sepsis.
AB  - To elucidate the involvement of hepatocyte growth factor (HGF) in systemic
      inflammatory response syndrome (SIRS) and sepsis, we investigated the plasma
      levels of HGF, as well as those of various proinflammatory and anti-inflammatory
      cytokines, in 50 patients who visited our emergency department (ED). The patients
      were divided into four groups, depending on the existence of SIRS and infection:
      group 1 (G1), no infection and no SIRS; group 2 (G2), infection and no SIRS;
      group 3 (G3), no infection and SIRS; and group 4 (G4), infection and SIRS (e.g.,
      sepsis). We found that plasma HGF levels in G4 were significantly higher than
      those in the groups without infection (G1 and G3). However, the correlations
      between HGF and other cytokines were comparatively low compared with those
      between any other pairs of cytokines, suggesting independent regulation of HGF
      production in vivo. High plasma HGF was significantly correlated with the
      presence of infection and with serum total bilirubin (TB) level on multivariate
      logistic regression analysis. Considering HGF's known functions, we speculated
      that high plasma HGF levels may indicate the occurrence or necessity for tissue
      protection and regeneration after acute systemic insults in sepsis.

PMID- 15160306
TI  - Macrolide-resistant genes of Streptococcus pyogenes isolated from the upper
      respiratory tract by polymerase chain reaction.
AB  - The growing number of macrolide-resistant strains of Streptococcus pyogenes is an
      increasing problem worldwide. This study evaluated 300 clinical isolates obtained
      from the upper respiratory tract. Minimal inhibitory concentrations (MICs) of
      erythromycin (EM), azithromycin (AZM), and clindamycin (CLDM), serotypes, and
      macrolide resistance genes of mefA, ermB, and ermTR were determined. The genetic
      relationship of EM-resistant and susceptible strains were also analyzed by pulsed
      field gel electrophoresis (PFGE). Twenty-nine (9.7%) EM-resistant S. pyogenes
      were identified. Of the 29 strains showing resistance to EM, 22 isolates (7.3%,
      MIC 3.13-12.5 microg/ml) expressed the mefA gene. The predominant serotypes among
      the mefA-positive isolates were T12, emm9 or T25, emm75-1. The two isolates
      (0.1%) that possessed the ermB gene were highly resistant to EM (MIC > 100
      microg/ml). The remaining five strains (1.6%) possessed the ermTR gene (MIC 3.13
      100 microg/ml). Restriction fragment polymorphism analyzed by pulsed-field gel
      electrophoresis (PFGE) by SmaI and ApaI digestions showed several clones among
      the mefA-positive S. pyogenes. Our findings suggest that the mefA gene is the
      predominant mechanism for macrolide resistance and that this gene is horizontally
      transmitted among M phenotype strains of S. pyogenes. Consequently, macrolides
      would not be the first drug of choice for treatment of tonsillitis and other S.
      pyogenes-related diseases. Physicians and researchers need to take into
      consideration the macrolide resistance of some strains of S. pyogenes.

PMID- 15160307
TI  - Early cytomegalovirus (CMV) gastrointestinal disease that developed 19 days after
      bone marrow transplantation, with a high-level of CMV antigenemia, of up to 1120
      cells/slide.
AB  - We report a 19-year-old male with acute myeloid leukemia who developed an early
      cytomegalovirus gastrointestinal disease with a high level of cytomegalovirus
      antigenemia after bone marrow transplantation. He underwent bone marrow
      transplantation from HLA-matched related donor. He developed acute graft-versus
      host disease on day 15, and he immediately went on prednisolone. The graft-versus
      host disease disappeared immediately, but he developed a severe epigastralgia on
      day 23. Although absolute neutrophil count was 0.5 x 10(9)/l, the pp65
      cytomegalovirus antigenemia increased up to 1120 cells/slide. The endoscope
      examination was performed on day 29 and it showed erosive gastritis, and
      microscopical examination revealed nuclear inclusion bodies and positive cells of
      cytomegalovirus antigen. Ganciclovir treatment was started, and it continued
      until negative cytomegalovirus antigenemia was confirmed. He consequently
      discharged to outpatient without late phase CMV diseases or recurrence of AML. We
      assessed that the patient had two risk factors. First, he was the cytomegalovirus
      seropositive patient and received bone marrow from seronegative donor. Second, he
      was treated with prednisolone for acute graft-versus-host disease. The
      ganciclovir treatment turned out to be successful, but the cytomegalovirus
      disease developed too early to start the antigenemia guided preemptive treatment.
      The high-risk patients could develop the early cytomegalovirus disease even
      though under the status of myelosuppression after bone marrow transplantation.

PMID- 15160308
TI  - Surveillance of vancomycin-resistant Enterococcus in hospitals in Ibaraki
      prefecture.
AB  - We surveyed the prevalence of vancomycin-resistant Enterococcus (VRE) in six
      hospitals in Ibaraki prefecture. Three hundred and fifty-five fecal specimens
      were examined and 18 Enterococcus intermediately resistant to vancomycin were
      isolated. All of them were vanC genotypes (16 vanC-1 and 2 vanC-2 genotypes) and
      susceptible or intermediately resistant to ampicillin, teicoplanin, linezolid,
      and quinupristin-dalfopristin. Neither the vanA nor vanB gene was detected. Two
      of the vanC genotypes were not motile. We concluded that VRE of either VanA or
      VanB phenotype or those highly resistant to the antibiotics commonly used against
      enterococcal infection were not epidemic in this prefecture to date. In addition,
      we consider that detection of vancomycin-resistant genes should be encouraged for
      the characterization of VRE, because the vanC genotypes are occasionally motility
      negative and can be misinterpreted as other Enterococcus species.

PMID- 15160309
TI  - In vitro exposure to macrolide antibiotics in Helicobacter pylori strains
      isolated from children.
AB  - Clarithromycin resistance of Helicobacter pylori is a serious problem in
      eradication therapy. We investigated whether the use of maclorides
      (clarithromycin, erythromycin, and azithromycin) induces clarithromycin
      resistance in the organism. Twenty H. pylori strains were isolated from pediatric
      patients with gastrointestinal symptoms. The minimum inhibitory concentrations
      (MICs) of each macrolide antibiotic were determined by the Etest. Among these, 17
      strains susceptible to macrolide antibiotics were used for the in vitro induction
      of drug resistance. In each of these 17 strains of H. pylori, 30-day exposure to
      clarithromycin in experiments for in vitro induction did not change the MIC of
      any antibiotic, nor did it induce either the A2143G or the A2144G mutation in the
      23S rRNA gene. These results suggest that the use of macrolide antibiotics does
      not induce clarithromycin resistance in H. pylori by 23S rRNA gene mutation.

PMID- 15160310
TI  - Survey of methicillin-resistant Staphylococcus aureus from neonates and the
      environment in the NICU.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor of nosocomial
      infection with compromised hosts including neonates. Currently, the prevalence of
      MRSA carriers among children is increasing in Japan. There are some reports of
      nosocomial infection caused by MRSA in a pediatric ward or neonatal intensive
      care unit (NICU). During 6 months (from January 2001 to June 2001), 37 MRSA
      strains were isolated from 37 neonates who were admitted in the NICU and 52 MRSA
      were strains isolated from NICU environments. We performed DNA typing of MRSA
      using an arbitrary primed-PCR method on these isolates. Thirty-seven clinical
      isolates were classified into four types (A type, 14; B type, 4; C type, 4; D
      type, 3; and others, 12). The A-type strains of MRSA continued to be isolated for
      more than 6 months. In the NICU environment, the detection rate of the A-type
      MRSA was 23.1% (12/52). The A-type strains were frequently isolated from
      environments around patients. The A-type strains of MRSA were prevalent in the
      NICU, probably due to nosocomial infection. Although none of the neonatal
      patients developed severe MRSA infection, the same genotype strains were
      persistently isolated during a period of more than 6 months from patients and the
      NICU environment around patients. Environmental control around neonatal patients
      is important to prevent nosocomial infection in the NICU.

PMID- 15160311
TI  - Legionella anisa and hospital water systems.

PMID- 15160313
TI  - Optimization of dose and dose regimen of biapenem based on pharmacokinetic and
      pharmacodynamic analysis.

PMID- 15160314
TI  - Spectroscopic investigation of the nickel-containing porphinoid cofactor F(430).
      Comparison of the free cofactor in the (+)1, (+)2 and (+)3 oxidation states with
      the cofactor bound to methyl-coenzyme M reductase in the silent, red and ox
      forms.
AB  - Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in
      methanogenic archaea. It contains the nickel porphinoid F(430), a prosthetic
      group that has been proposed to be directly involved in the catalytic cycle by
      the direct binding and subsequent reduction of the substrate methyl-coenzyme M.
      The active enzyme (MCRred1) can be generated in vivo and in vitro by reduction
      from MCRox1, which is an inactive form of the enzyme. Both the MCRred1 and MCRox1
      forms have been proposed to contain F(430) in the Ni(I) oxidation state on the
      basis of EPR and ENDOR data. In order to further address the oxidation state of
      the Ni center in F(430), variable-temperature, variable-field magnetic circular
      dichroism (VTVH MCD), coupled with parallel absorption and EPR studies, have been
      used to compare the electronic and magnetic properties of MCRred1, MCRox1, and
      various EPR silent forms of MCR, with those of the isolated penta-methylated
      cofactor (F(430)M) in the (+)1, (+)2 and (+)3 oxidation states. The results
      confirm Ni(I) assignments for MCRred1 and MCRred2 forms of MCR and reveal charge
      transfer transitions involving the Ni d orbitals and the macrocycle pi orbitals
      that are unique to Ni(I) forms of F(430). Ligand field transitions associated
      with S=1 Ni(II) centers are assigned in the near-IR MCD spectra of MCRox1-silent
      and MCR-silent, and the splitting in the lowest energy d-d transition is shown to
      correlate qualitatively with assessments of the zero-field splitting parameters
      determined by analysis of VTVH MCD saturation magnetization data. The MCD studies
      also support rationalization of MCRox1 as a tetragonally compressed Ni(III)
      center with an axial thiolate ligand or a coupled Ni(II)-thiyl radical species,
      with the reality probably lying between these two extremes. The reinterpretation
      of MCRox1 as a formal Ni(III) species rather than an Ni(I) species obviates the
      need to invoke a two-electron reduction of the F(430) macrocyclic ligand on
      reductive activation of MCRox1 to yield MCRred1.

PMID- 15160315
TI  - The solution structure of rat Abeta-(1-28) and its interaction with zinc ion:
      insights into the scarcity of amyloid deposition in aged rat brain.
AB  - The amyloid beta-peptide (Abeta) is a major component of insoluble amyloid
      deposits in Alzheimer's disease, and the ability of the beta-peptide to exist in
      different conformations is dependent on residues 1-28 [beta-(1-28)]. However,
      different from humans, no Abeta amyloid deposition has been found in aged rats'
      brains. Studying the three-dimensional solution structure of rat Abeta-(1-28) and
      the binding circumstance of Zn(2+) is beneficial to a clear understanding of the
      potential role of Zn(2+) in Alzheimer-associated neuropathogenesis and to suggest
      why there is no amyloid deposition in aged rats' brains. Here we used nuclear
      magnetic resonance (NMR) spectroscopy to determine the solution structure of rat
      Abeta-(1-28) and the binding constant of Zn(2+) to rat Abeta-(1-28). Our results
      suggest that (1) the three-dimensional solution structure of rat Abeta-(1-28) is
      more stable than that of human Abeta-(1-28) in DMSO- d(6) and that a helical
      region from Glu16 to Val24 exists in the rat Abeta-(1-28); (2) the affinity of
      Zn(2+) for rat Abeta-(1-28) is lower than that for human Abeta-(1-28) and the NMR
      data suggest that Arg13, His6, and His14 residues provide the primary binding
      sites for Zn(2+); and (3) the proper binding of Zn(2+) to rat Abeta-(1-28) can
      induce the peptide to change to a more stable conformation.

PMID- 15160316
TI  - Potential risk factors for prolonged recovery following whiplash injury.
AB  - A retrospective analysis of insurance data was made of 600 individuals claiming
      compensation for whiplash following motor vehicle accidents. Three hundred
      randomly selected claimants who had settled their injury claims within 9 months
      of the accident were compared with 300 who had settled more than 24 months after
      the accident. We compared the two groups to identify possible risk factors for
      prolonged recovery, for which settlement time greater than 24 months was a
      marker. Variables considered included demographic factors, type of collision,
      degree of vehicle damage, workers compensation, prior claim or neck disability,
      treatment and time to settlement. Consulting a solicitor was associated with a
      highly significant, four-fold increase of late settlement of the claim. A
      concurrent workers' compensation claim, prior neck disability and undergoing
      physiotherapy or chiropractic treatment were weakly associated with late
      settlement. The degree of damage to the vehicle (as indicated by cost of repairs)
      was not a significant predictor of late settlement. Late settlement may be the
      direct effect of legal intervention, independent of the severity of the injury.
      Whilst the financial benefit to the claimant of consulting a solicitor is
      apparent, the benefit of prolonged disability is not. It may be to the advantage
      of both insurers and claimants if those likely to proceed to late settlement
      could be recognised early and their claims settled expeditiously.

PMID- 15160319
TI  - Zoledronate in a patient with pamidronate refractory hypercalcemia syndrome.
AB  - Hypercalcemia of malignancy remains a common metabolic complication of advanced
      cancer often resulting in considerable morbidity and diminishing life quality in
      the later stages of disease. Bisphosphonates, especially zoledronic acid, are
      potent inhibitors of bone resorption and are the most effective therapy for
      hypercalcemia of malignancy. We report on the course of disease in a 51-year-old
      woman who presented with metastatic breast cancer that had relapsed to the liver.
      The patient suffered from a pamidronate-refractory paraneoplastic hypercalcemia,
      which caused a confused mental status and compromised her already severely
      limited life quality. Only with the introduction of zoledronate could the
      patient's hypercalcemia be normalized with consecutive regain of an acceptable
      life quality.

PMID- 15160317
TI  - The use of recombinant activated coagulation factor VII for spine surgery.
AB  - This article focuses on our current understanding of the role of activated
      coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the
      efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use
      of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the
      European Union and the USA) for patients with hemophilia and inhibitors
      (antibodies) to coagulation factors VIII or IX. High circulating concentrations
      of FVIIa, achieved by exogenous administration, initiate hemostasis by combining
      with tissue factor at the site of injury, producing thrombin, activating
      platelets and coagulation factors II, IX and X, thus providing for the full
      thrombin burst that is essential for hemostasis. This "bypass" therapy has led
      some clinicians to use rFVIIa "off-label" for disorders of hemostasis other than
      hemophilia. Based on clinical experience, case reports and limited information
      from clinical trials, rFVIIa may be efficacious in states of decreased
      concentration of coagulation factors, thrombocytopenia, and at least some states
      of altered platelet function. The former two can occur intra-operatively during
      spinal surgery as a consequence of substantial blood loss and normal consumption.
      Preliminary reports have indicated that rFVIIa does not increase the
      perioperative incidence of thromboembolic events. However, full reports from
      large clinical trials regarding the efficacy and safety of rFVIIa in settings
      other than hemophilia have yet to appear in peer-reviewed publications. Until
      adequate data demonstrating safety and efficacy are fully reported, it would seem
      appropriate to reserve the use of rFVIIa in spinal surgery to those instances
      where conventional therapy cannot provide adequate hemostasis, and "rescue"
      therapy is required.

PMID- 15160320
TI  - [Future development of hospital structure].

PMID- 15160318
TI  - Resolution of refractory chemotherapy-induced diarrhea (CID) with octreotide long
      acting formulation in cancer patients: 11 case studies.
AB  - PURPOSE: Subcutaneous (SC) octreotide has been shown to effectively relieve
      chemotherapy-induced diarrhea (CID) refractory to conventional therapy but
      requires t.i.d. injections. A microencapsulated, long-acting formulation (LAR) of
      octreotide has been developed for once-monthly intramuscular (IM) dosing.
      Efficacy in resolving severe diarrhea and preventing further episodes of diarrhea
      in cancer patients was explored. PATIENTS AND METHODS: Patients with advanced
      cancer who developed CID and failed conventional antidiarrheal therapy
      (loperamide + diphenoxylate-atropine) received octreotide LAR IM. The starting
      dose was either 20 or 30 mg with possible dose escalation from 20 to 30 mg and
      from 30 to 40 mg. Treatment was repeated every 28 days during chemotherapy.
      RESULTS: Complete resolution of diarrhea within 1 to 4 weeks from injection time
      was seen in all cases with octreotide LAR 30 mg. With a subsequent prophylactic
      injection once every 28 days, CID was limited to NCI grade 1. This resulted in
      increased patient quality of life (QOL) and allowed better patient compliance
      with therapy. Therapy could then be completed at full dose and on schedule after
      resolution of often debilitating diarrhea. CONCLUSION: The ability of octreotide
      LAR 30 mg to speed the resolution of CID and limit further episodes of diarrhea
      to infrequent NCI grade 1 controlled with loperamide (prn) suggests that long
      acting somatostatin homologues have the potential to be useful in the secondary
      prevention of diarrhea in patients undergoing chemotherapy.

PMID- 15160321
TI  - [Acceptance of a patient passport in secondary prevention of coronary heart
      disease].
AB  - BACKGROUND AND OBJECTIVE: Over the long term a large percentage of patients
      exhibit inadequately managed cardiovascular risk factors following an acute
      cardiac event. It remains unclear whether the patients would accept a health pass
      and which sociodemographic variables have an effect on the number of its users.
      PATIENTS AND METHODS: 437 patients (25% women, 69 +/- 10 years; 75% men 63 +/- 10
      years) with diagnosed coronary heart disease were issued a health pass before
      being discharged from in-patient rehabilitation care. Besides their medical
      history, the passes contained the patients' latest values for hypertension,
      glucose, lipids, body mass index (kg/m(2)), and smoking. How many patients
      actually use the health pass was checked by the patients' physicians after 3, 6,
      and 12 months. In addition, cardioprotective drugs and cardiac events were
      logged. RESULTS: 185 (44%) of the patients used the pass continually over the
      course of one year. These patients tended to be older (> or = 60 years vs. < 60
      years, p = 0.023), to be white-collar workers (white-collar vs. blue-collar, p =
      0.043), and to have a higher level of education (> 10th class vs. < or = 10th
      class, p = 0.039) compared to "non-users". CONCLUSION: The acceptance of a
      passport is low, because fewer than half the patients used it in connection with
      the secondary prevention of coronary heart disease. Therefore the health pass in
      its present form did not show up as a useful device in patient care, particularly
      in single persons and those of a low sociodemographic status.

PMID- 15160323
TI  - [Interventional catheter closure of persistent foramen ovale (PFO) in a patient
      with paradoxical embolism and Brugada's syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 41-year-man was admitted because of acute
      bluish-grey skin discoloration in cold sensation in the right hand. His brother
      had suffered sudden cardiac death, aged 42 years. INVESTIGATIONS: Angiography
      demonstrated embolic occlusion of the digital artery of the right thumb.
      Transesophageal echocardiography showed a persistent foramen ovale (PFO) with an
      aneurysm of the atrial septum (ASA) with marked right-to-left shunt of contrast
      medium during a Valsalva maneuvre as well as two smaller septal fenestrations.
      There was no evidence of any other source of embolism. The resting
      electrocardiogram showed an incomplete right bundle branch block with ST
      elevations in V (1)-V (3), changes like those described in Brugada's syndrome.
      TREATMENT AND COURSE: Paradoxical embolism having been demonstrated, the PFO with
      ASA were closed with a percutaneously introduced Helex septum occluder. Later an
      implantable cardioverter-defibrillator (ICD) was introduced. CONCLUSIONS: A PFO,
      particularly if associated with an atrial aneurysm, is an important site of
      paradoxical embolism. In symptomatic patients percutaneous transcatheter septal
      occlusion should be considered preceding any ICD insertion thought necessary for
      concurrent Brugada's syndrome.

PMID- 15160322
TI  - [Celecoxib in the symptomatic treatment of active osteo- or rheumatoid arthritis.
      Results of a post-marketing surveillance].
AB  - BACKGROUND AND OBJECTIVE: The introduction of cyclooxygenase (COX)-2 selective
      drugs now offers physicians the possibility of a adequate analgesic and anti
      inflammatory therapy. Drug induced side effects typically associated with NSAIDs
      are reduced. Using a post-marketing surveillance study (PSS) efficacy and
      tolerability of the COX-2-selective drug Celecoxib was evaluated. Patients were
      not restricted in the use of other medication. PATIENTS AND METHODS: By means of
      a prospective, non-intervening PSS patients mainly suffering from musculoskeletal
      conditions such as osteoarthritis (70.5 %) or rheumatoid arthritis (19.6 %) were
      examined by about 12,000 physicians. The median observation period was almost 5
      weeks. RESULTS: In total 70236 patients (42 % males, 58 % females, mean age 60.3
      years) were assessed. About 87 % of the patients were adequately treated with a
      daily dose of 200 mg. The tolerability of the treatment was judged to be "good"
      to "very good" by the physicians in 97 % and by the patients in 96 % of the
      cases. The overall incidence of undesirable events (UE) with or without potential
      causal relationship with the study medication was 2.8 % (1,955 patients), severe
      UEs manifesting in 0.3 % (223) of all patients. CONCLUSIONS: Overall, the PSS
      confirms the evident subjective efficacy and tolerability by both the physician's
      and the patient's overall assessment.

PMID- 15160324
TI  - [Effect of the new drug provisions on the drug treatment of narcolepsy].

PMID- 15160325
TI  - [New approaches in the treatment of hepatitis B].

PMID- 15160326
TI  - [The healthcare scene in Germany--a market in upheaval].

PMID- 15160327
TI  - [Is there a disease picture "central fever"?].

PMID- 15160329
TI  - Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence:
      the potential role of partial breast irradiation.
AB  - Mastectomy is the current standard of care for in-breast local recurrence of
      breast carcinoma. The objective of the current study was to critically review the
      rationale for and the theoretic and actual risks and benefits of repeat breast
      conserving surgery followed by partial breast irradiation (PBI) for in-breast
      local recurrence of breast carcinoma. The main outcomes of interest were local
      control and survival after in-breast local recurrence and side effects,
      complications, and cosmesis after reirradiation of the breast. The risk of local
      recurrence was not found to be eliminated with mastectomy; approximately 2-32% of
      patients treated with mastectomy develop a chest wall recurrence. The
      interpretation of local control rates in evaluating repeat breast-conserving
      surgery studies is difficult because of the lack of information regarding
      preoperative diagnostic mammography to rule out concurrent multicentric disease
      and microscopic margin status after surgery. Rates of subsequent local recurrence
      in these studies appeared to be between 19-50%, similar to reported rates of in
      breast local recurrence in patients with a first diagnosis of breast carcinoma
      who were treated with conservative surgery without irradiation. Early follow-up
      studies of breast reirradiation suggest that catheter-based interstitial
      brachytherapy and standard external beam radiation therapy can be delivered to
      the breast more than once without significant side effects in most patients and
      with acceptable cosmesis in some patients. Mastectomy may not be necessary in all
      patients with an in-breast local recurrence of breast carcinoma. Recent advances
      in conformal radiation delivery and single-center published reports concerning
      repeat breast-conserving therapy support well designed prospective trials to
      formally test this hypothesis.

PMID- 15160328
TI  - ["New" serum marker for cardiovascular risk].

PMID- 15160330
TI  - The role of Fas ligand and transforming growth factor beta in tumor progression:
      molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential
      targets for cancer therapy.
AB  - Despite the fact that expression of Fas ligand (FasL) in cytotoxic T lymphocytes
      (CTLs) and in natural killer (NK) cells plays an important role in Fas-mediated
      tumor killing, During tumor progression FasL-expressing tumor cells are involved
      in counterattacking to kill tumor-infiltrating lymphocytes (TILs). Soluble FasL
      levels also increase with tumor progression in solid tumors, and this increase
      inhibits Fas-mediated tumor killing by CTLs and NK cells. The increased
      expression of FasL in tumor cells is associated with decreased expression of Fas;
      and the promoter region of the FASL gene is regulated by transcription factors,
      such as neuronal factor kappaB (NF-kappaB) and AP-1, in the tumor
      microenvironment. Although the ratio of FasL expression to Fas expression in
      tumor cells is not strongly related to the induction of apoptosis in TILs,
      increased expression of FasL is associated with decreased Fas levels in tumor
      cells that can escape immune surveillance and facilitate tumor progression and
      metastasis. Transforming growth factor beta (TGF-beta) is a potent growth
      inhibitor and has tumor-suppressing activity in the early phases of
      carcinogenesis. During subsequent tumor progression, the increased secretion of
      TGF-beta by both tumor cells and, in a paracrine fashion, stromal cells, is
      involved in the enhancement of tumor invasion and metastasis accompanied by
      immunosuppression. Herein, the authors review the clinical significance of FasL
      and TGF-beta expression patterns as features of immune privilege accompanying
      tumor progression in the tumor microenvironment. Potential strategies for
      identifying which molecules can serve as targets for effective antitumor therapy
      also are discussed.

PMID- 15160331
TI  - The cognitive sequelae of standard-dose adjuvant chemotherapy in women with
      breast carcinoma: results of a prospective, randomized, longitudinal trial.
AB  - BACKGROUND: Retrospective trials have reported that chemotherapy-induced
      cognitive dysfunction was experienced by a subset of patients with breast
      carcinoma. However, recent evidence indicated that a subset also exhibited
      impaired cognitive function at baseline, before the start of chemotherapy. A
      prospective, longitudinal trial that incorporates baseline neuropsychologic
      evaluations is necessary to determine to what extent cognitive dysfunction is
      attributable to chemotherapy in this population. METHODS: Eighteen women with
      breast carcinoma underwent a comprehensive neuropsychologic evaluation before
      treatment and at short-term and long-term intervals after chemotherapy. The
      incidence, nature, severity, and chronicity of cognitive dysfunction developing
      in patients with breast carcinoma treated with a standard dose of adjuvant
      chemotherapy were assessed. RESULTS: Before the start of systemic therapy, 33% of
      women in the current cohort exhibited cognitive impairment. At the short-term
      postchemotherapy time point, 61% of the cohort exhibited a decline relative to
      baseline in 1 or more domains of cognitive functioning and reported greater
      difficulty in maintaining their ability to work. The most common domains of
      cognitive dysfunction were related to attention, learning, and processing speed.
      At the long-term postchemotherapy time point, approximately 50% of patients who
      experienced declines in cognitive function demonstrated improvement, whereas 50%
      remained stable. Self-reported ability to perform work-related activities also
      improved over this interval. Neither impairment at baseline nor subsequent
      treatment-related cognitive decline exhibited any statistically significant
      correlation with affective well-being or with demographic or clinical
      characteristics. CONCLUSIONS: The current study is the first longitudinal trial
      to report evidence of an association between cognitive dysfunction and
      chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The
      importance of using prospective research designs, appropriate cognitive measures,
      and statistical methods to evaluate subgroup effects was discussed.
      Identification of mechanisms associated with cognitive dysfunction and of risk
      factors contributing to subgroup vulnerability is necessary.

PMID- 15160333
TI  - The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and
      breast carcinoma risk among postmenopausal women: a case-control study.
AB  - BACKGROUND: Statin use has increased dramatically in the U.S. in the past decade.
      Animal and mechanistic studies suggested that statins may have an inhibitory
      effect on cancer proliferation, including breast carcinoma. However, statins have
      been found to be carcinogenic in rodents and one clinical trial found an excess
      of breast carcinoma cases in the treatment group. METHODS: The current study
      assessed whether the use of statins altered the risk of breast carcinoma in older
      women. The population-based, case-control study comprised female residents from
      three western Washington State counties. Cases included 975 women identified from
      the Cancer Surveillance System who were diagnosed with primary invasive breast
      carcinoma between 1997-1999, whose names appeared on a list of Social Security
      recipients provided by the Centers for Medicare and Medicaid Services. The cases
      were ages 65-79 years at the time of diagnosis. The comparison group was
      comprised of 1007 women without breast carcinoma who were randomly selected from
      the same list of Social Security recipients. Information pertaining to statin
      use, medical history, and health behaviors was ascertained through an in-person
      interview. RESULTS: Compared with nonusers, women who were currently using
      statins or had ever used statins were not found to be at an increased risk for
      breast carcinoma (odds ratios [OR] = 0.9; 95% confidence interval [95% CI], 0.7
      1.2). There was some indication that long-term statin use (> 5 years) was related
      to a slight decrease in breast carcinoma risk (OR = 0.7; 95% CI, 0.4-1.0).
      CONCLUSIONS: The results of the current study provided some degree of reassurance
      to the increasing numbers of women using statins that such use is not associated
      with an increased risk of breast carcinoma. Although the data gave some support
      to a reduced risk of breast carcinoma among long-term users of statins, further
      research is needed to confirm this association.

PMID- 15160332
TI  - Diversity matters: Unique populations of women and breast cancer screening.
AB  - BACKGROUND: Ethnic differences in breast cancer screening behaviors are well
      established. However, there is a lack of understanding regarding exactly what
      causes these differences and which characteristics in low-screening populations
      should be targeted in an effort to modify screening behavior. METHODS: Stratified
      cluster sampling was used to recruit 1364 women (ages 50-70 years) from 6 ethnic
      groups: African-American women; U.S.-born white women; English-speaking
      Caribbean, Haitian, and Dominican women; and immigrant Eastern-European women. In
      interviews, respondents provided information concerning demographic and
      structural variables related to mammogram utilization (age, education, income,
      marital status, physician recommendation, access, and insurance) and a set of
      cognitive variables (fatalism, perception of personal risk, health beliefs
      concerning cancer) and socioemotional variables (stress, cancer worry,
      embarrassment, and pain). RESULTS: For data analysis, the authors used a 2-step
      logistic regression with frequency of mammograms over a 10-year period (< or = 4
      mammograms over 10 years or > or = 5 mammograms over 10 years) as a dependent
      variable. U.S.-born African-American women and Dominican women were screened as
      frequently as European-American women, but the remaining minority groups were
      screened with less frequency. With one exception, ethnicity ceased to predict
      screening frequency once cognitive and emotional variables were controlled.
      CONCLUSIONS: Although women from clearly operationalized ethnic groups continue
      to screen at rates substantially below those of the majority groups, these
      differences appear to be explained substantially by differences in psychologic
      variables. This is encouraging because, rather than targeting culture for
      intervention, variables can be targeted that are amenable to change, such as
      emotions and beliefs.

PMID- 15160335
TI  - Hormone replacement therapy in relation to breast carcinoma incidence rate
      ratios: a prospective Danish cohort study.
AB  - BACKGROUND: The goal of the current study was to investigate the relation between
      hormone replacement therapy (HRT) and breast carcinoma in a prospective study
      cohort. Particular attention was paid to the type of HRT used and to the
      association of HRT type with estrogen receptor status and tumor histology.
      METHODS: Between 1993 and 1997, a total of 29,875 women were enrolled in the
      Danish Cancer Society's prospective "Diet, Cancer and Health" study. Among 23,618
      women who were assumed to be postmenopausal and for whom information on HRT use
      was available, we identified 423 cases of breast carcinoma over a median follow
      up period of 4.8 years. Statistical analyses were based on the Cox proportional
      hazards model, with age serving as the time parameter. RESULTS: The breast
      carcinoma incidence rate ratio (IRR) was 2.22 (95% confidence interval [CI], 1.80
      2.75) for users of HRT at baseline compared with women who never received HRT.
      Among HRT users (relative to nonusers), the IRR for estrogen receptor-positive
      tumors (2.38; 95% CI, 1.84-3.06) was greater than the IRR for estrogen receptor
      negative tumors (1.56; 95% CI, 1.00-2.43). HRT use at baseline also was analyzed
      in relation to the incidence of lobular carcinoma and the incidence of ductal
      carcinoma; the adjusted IRR associated with HRT use was 3.53 (95% CI, 1.94-6.41)
      for lobular carcinoma and 2.10 (95% CI, 1.64-2.70) for ductal carcinoma. The
      likelihood of developing estrogen receptor-positive breast carcinoma was found to
      depend significantly on the type of HRT regimen used (P = 0.03), with women
      receiving continuous therapy having the greatest probability of developing
      estrogen receptor-positive disease. CONCLUSIONS: An increased breast carcinoma
      IRR was found to be associated with current HRT use. In addition, relative to
      other types of HRT regimens, continuous estrogen + progestin regimens were found
      to be associated with an increased risk of breast carcinoma, and particularly
      estrogen receptor-positive breast carcinoma.

PMID- 15160334
TI  - The prognostic significance of multiple morphologic features and biologic markers
      in ductal carcinoma in situ of the breast: a study of a large cohort of patients
      treated with surgery alone.
AB  - BACKGROUND: A number of conventional histopathologic features have been
      associated with recurrence of ductal carcinoma in situ (DCIS) after surgery alone
      and are included in the Van Nuys Pathologic Classification and Prognostic Index.
      To the authors' knowledge, very little is known regarding the prognostic
      significance of the many biologic markers that have been studied in DCIS in the
      past decade. METHODS: Clinical and pathologic data were analyzed from 151
      patients who underwent wide local excision alone for DCIS that was diagnosed by
      mammography or as an incidental finding between 1982 and 2000. Using local
      disease recurrence as an endpoint, the authors sought to determine the prognostic
      significance of a large number of histopathologic parameters as well as biologic
      markers (estrogen receptor [ER], progesterone receptor [PR], p53, HER-2/neu, Ki
      67, p21, and bcl-2), as determined by immunohistochemical staining of
      contemporary or archival tissue. RESULTS: With a median follow-up of 65 months,
      42 recurrences were reported to occur between 11 months and 97 months after
      definitive surgery. In a univariate analysis, tumor size, Van Nuys pathologic
      classification, and degree of necrosis demonstrated significant correlations with
      the rate of recurrence. Tumor size, necrosis, nuclear grade, and comedonecrosis
      were found to be associated significantly with the time to disease recurrence.
      None of the biologic markers demonstrated a significant association with the rate
      of recurrence or the time to disease recurrence. In a multivariate analysis, only
      large tumor size (Van Nuys 2 or 3) and higher degrees of necrosis (Van Nuys 2 or
      3) were found to be associated significantly with both the rate of recurrence and
      the time to recurrence. No biologic marker showed a significant correlation with
      recurrence. Using Classification and Regression-Tree Analysis and Tree-Structured
      Survival Analysis, PR > 3.5% and bcl-2 < 97.5% were associated with a higher
      recurrence rate in the subgroup of patients with small tumor size (Van Nuys size
      1) and higher degrees of tumor necrosis (Van Nuys 2 or 3). CONCLUSIONS: The
      current results confirmed the value of conventional histopathologic parameters,
      as outlined in the Van Nuys classification system, in predicting local recurrence
      of DCIS. Using traditional logistic analyses, no significant correlation was
      found between a variety of biologic markers and disease recurrence.

PMID- 15160336
TI  - Breast carcinoma screening and risk perception among women at increased risk for
      breast carcinoma: results from a national survey.
AB  - BACKGROUND: The Gail model is validated to estimate breast carcinoma risk. The
      authors assessed the association of Gail risk scores with screening and cancer
      risk perception. METHODS: Using the 2000 National Health Interview Survey, the
      authors studied women ages 41-70 without a cancer history. Gail scores > or =
      1.66% defined increased risk. The authors used logistic regression to assess
      associations between breast carcinoma risk and previous and recent (< or = 1
      year) mammography and clinical breast examination (CBE). RESULTS: Of 6410 women,
      15.7% had increased risk. High-risk women more frequently reported previous
      mammograms (94% vs. 85%; P < 0.0001), previous CBE (93% vs. 88%; P < 0.0001),
      recent mammograms (70% vs. 54%; P < 0.0001), recent CBE (71% vs. 61%; P <
      0.0001), and high cancer risk perception (20% vs. 9%; P < 0.0001). However, 30%
      of high-risk women had not received a recent mammogram. After adjustment for
      sociodemographic factors, access to care factors, and cancer risk perception,
      high-risk women remained more likely to have received recent mammography
      (adjusted odds ratio [OR], 1.45, 95% confidence interval [95% CI], 1.19-1.77),
      recent CBE (OR, 1.32; 95% CI, 1.08-1.61]), and previous mammography than average
      risk women. The authors observed an interaction between risk and age, with women
      ages 41-49 years more frequently reporting previous mammography (OR, 4.79; 95%
      CI, 1.55-4.81) than average-risk, same-age women. For women age > or = 50 years,
      the odds of previous mammography were similar regardless of risk. CONCLUSIONS: In
      a nationally representative sample, 15.7% of women had increased breast carcinoma
      risk using the Gail model. High-risk women perceived higher cancer risk and more
      often received screening. However, nearly one in three high-risk women did not
      receive recent screening and most of these women did not perceive increased risk.

PMID- 15160337
TI  - Preoperative induction of CPT-11 and cisplatin chemotherapy followed by
      chemoradiotherapy in patients with locoregional carcinoma of the esophagus or
      gastroesophageal junction.
AB  - BACKGROUND: Patients with localized esophageal carcinoma often develop
      locoregional and distant disease recurrence. The current study investigated the
      outcome of a new chemotherapy combination as induction therapy before
      chemoradiotherapy. METHODS: Forty-three patients with resectable carcinoma of the
      esophagus or gastroesophageal junction were enrolled. Most of the tumors were
      endoscopic ultrasonography (EUS) (EUS)T3 (84%) and (EUS)N1 (63%). The patients
      received < or = 2 6-week cycles of CPT-11 and cisplatin followed by
      chemoradiotherapy (45 grays with 5-fluorouracil and paclitaxel). Five to six
      weeks after chemoradiotherapy, the patients underwent staging and surgery. The
      feasibility, curative resection rates, overall and disease-free survival rates,
      rate of significant pathologic response, and patterns of disease recurrence were
      assessed. RESULTS: Of the 43 patients, 39 (91%) underwent an R0 resection. Two
      patients (5%) died after surgery. A pathologic complete response (pathCR) was
      observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition,
      16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in
      the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N
      classifications with surgical T and N classifications demonstrated significant
      down-staging (P < 0.01). The median survival period of all 43 patients was 22.1
      months. Patients who had achieved a pathCR or pathPR had a longer median survival
      (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52).
      None of the clinical parameters examined were found to correlate with survival or
      pathologic response. CONCLUSIONS: CPT-11-based induction chemotherapy resulted in
      substantial pathCR and pathPR rates, both of which lead to a favorable survival
      outcome. The three-step strategy needs to be developed further, with the
      investigation of targeted therapies with chemotherapy and radiotherapy.

PMID- 15160339
TI  - Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate.
AB  - BACKGROUND: The Gleason grading system uniquely combines data from different
      areas of carcinoma in the same prostate specimen. Prostatic adenocarcinoma often
      is multifocal, and different Gleason grades may be present in different foci. The
      current study was undertaken to compare the Gleason grades of individual
      adenocarcinoma foci in a given specimen with the overall Gleason grades (primary
      and secondary) of that specimen. METHODS: Data were obtained from 115 consecutive
      radical prostatectomy specimens via whole-mount processing and complete
      sectioning. Diagrams were constructed by tracing the outline of each whole-mount
      section, and tumor maps subsequently were generated. The largest focus was
      considered the index tumor. Each prostatectomy specimen was assigned primary and
      secondary Gleason grades, and each tumor focus was assigned its own primary and
      secondary Gleason grades. Tumor volume was measured using the grid method.
      RESULTS: Two or more adenocarcinoma foci were present in 87% of all specimens (2
      foci, n = 20; 3 foci, n = 33; 4 foci, n = 17; 5 foci, n = 13; > 5 foci, n = 17).
      Specimens (n = 15) containing a single tumor were excluded from further analysis.
      Among the remaining specimens (n = 100), all tumor foci had Gleason grades that
      were the same as the corresponding overall Gleason grades in only 9 cases (9%).
      The Gleason score (i.e., the sum of the primary and secondary grades) of the
      index tumor was correlated with the overall Gleason score in 68% of specimens.
      The primary grade of the index tumor was the same as the overall primary grade in
      97 specimens, whereas the secondary grade of the index tumor was the same as the
      overall secondary grade in only 68 specimens. The primary and secondary grades of
      the index tumor, compared with the overall Gleason primary and secondary grades,
      were reversed in 17 specimens. CONCLUSIONS: The findings of the current study
      demonstrated the histologic heterogeneity of multifocal prostate malignancies.
      Although the Gleason grading system was used to determine an overall score for
      prostate carcinoma within a specimen, the scores of individual tumors, including
      index tumors, often did not agree with this overall score. These findings may
      have implications with respect to future biomarker and tissue array studies.

PMID- 15160338
TI  - Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma.
AB  - BACKGROUND: The goal of the current study was to evaluate the objective response
      rate and toxicity associated with the oral fluoropyrimidine S-1 (a combination of
      tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) in patients with
      previously untreated metastatic colorectal carcinoma. METHODS: Thirty-eight
      patients were enrolled in the study. S-1 was administered orally at a dose of 40
      mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was
      repeated every 6 weeks unless disease progression was observed. RESULTS: A
      combined total of 173 courses of S-1 were administered to the 38 enrolled
      patients. The median number of courses administered to a given patient was 3.5
      (range, 1-18). Although no patient exhibited a complete response to treatment, 15
      had partial responses (response rate, 39.5%; 95% confidence interval, 24.0
      56.6%). In addition, 5 patients had minor responses, and 14 had stable disease.
      Four patients were found to have progressive disease after two courses of
      treatment. The median survival time was 358 days (95% confidence interval, 305
      490 days), and the 1-year survival rate was 47.4%. The most common adverse
      reactions included myelosuppression and gastrointestinal toxicity; most cases
      involved Grade 1 or 2 toxicity, but Grade 3 toxicities (anemia [7.9% of
      patients], neutropenia [5.3% of patients], diarrhea [2.6% of patients], and
      abnormal bilirubin levels [7.9% of patients]) also were noted. Neither Grade 4
      toxicity nor treatment-related death was observed during the study. CONCLUSIONS:
      Orally administered S-1 is active against metastatic colorectal carcinoma and has
      an acceptable toxicity profile. This promising agent has the potential to become
      a valuable chemotherapeutic option.

PMID- 15160340
TI  - Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and
      their value in predicting tumor progression.
AB  - BACKGROUND: Cell cycle proteins are important markers in predicting tumor
      behavior in urothelial carcinoma of the bladder. The objectives of this study
      were 1) to determine the expression levels of some of those markers in a series
      of patients with bladder carcinoma, 2) to define their value in distinguishing
      T1a (minimally invasive) from T1b (invasive) tumors, and 3) to evaluate their use
      as predictive factors in the progression of T1a and T1b tumors. METHODS: Tumor
      specimens from 101 patients were included (22 Ta specimens, 34 T1a specimens, 15
      T1b specimens, and 30 T2 specimens). A tissue microarray from the 101 paraffin
      embedded tissue blocks was constructed. Immunohistochemistry for p16, p27, p21,
      p53, cyclin D1, and Ki-67 were performed. To evaluate T1a and T1b tumor
      progression, clinical and follow-up data were available for all 49 patients.
      RESULTS: Cyclin D1 and p27 were the only markers that showed a significant
      association with tumor stage and tumor grade (cyclin D1: P = 0.002 and P > 0.00,
      respectively; p27: P = 0.024 and P = 0.031, respectively). The results indicated
      that a combination of p21 (odds ratio, 5.7; 95% confidence interval [95% CI], 1.3
      24.8 [P = 0.022]) and p16 (odds ratio, 3.7; 95% CI, 0.8-16.5 [P = 0.081]) may
      have potential use in distinguishing T1b tumors from T1a tumors. Finally, none of
      the markers examined were found to have predictive value for T1a and T1b tumor
      progression. CONCLUSIONS: The expression of cyclin D1 and p27 was associated with
      the most important prognostic factors (tumor stage and grade). The combination of
      p21 and p16 may have value in distinguishing T1b tumors from T1a tumors, although
      this finding must be evaluated in much larger series. Finally, none of the
      markers studied appeared to have predictive value for disease progression in
      patients with T1a and T1b urothelial bladder tumors.

PMID- 15160341
TI  - Prognostic significance of erythropoietin expression in human endometrial
      carcinoma.
AB  - BACKGROUND: Erythropoietin (Epo), which is induced by hypoxia, controls
      erythropoiesis and protects neurons from hypoxic damage. Hypoxia in malignant
      disease is associated with invasion, metastasis, and resistance to therapy. The
      authors recently demonstrated hypoxia-stimulated expression of Epo and Epo
      receptor (EpoR) in human breast and cervical carcinomas, suggesting a role for
      autocrine Epo signaling in the hypoxic adaptations of carcinomas. METHODS: The
      authors characterized the expression of Epo, EpoR, hypoxia-inducible factor (HIF)
      1alpha, estrogen receptor (ER), and progesterone receptor (PR) by
      immunohistochemical methods using endometrial carcinoma samples from 107 women
      and benign endometrial samples from 59 women in various phases of the menstrual
      cycle. They then analyzed potential correlations of Epo and EpoR immunostaining
      and clinicopathologic tumor features with outcome. RESULTS: In benign endometrial
      tissue samples, Epo and EpoR expression increased over the course of the cycle,
      with the highest levels observed in the late secretory phase. Epo expression in
      benign endometrial samples showed a negative correlation with ER and PR
      expression. The authors found Epo and EpoR expression in 95.3 % and 100% of
      endometrial carcinoma samples, respectively. Increased EpoR, but not Epo,
      expression in tumors was associated with advanced-stage disease, lymphovascular
      invasion, lymph node metastasis, and loss of ER expression. Increased Epo
      expression was observed in perinecrotic tumor regions in a pattern similar to the
      HIF-1alpha expression pattern. Increased Epo expression was significantly
      associated with adverse clinical outcome on both univariate and multivariate
      analysis. CONCLUSIONS: Hypoxia-inducible autocrine Epo signaling in endometrial
      carcinoma may contribute to tumor progression and increased aggressiveness.
      Increased Epo expression in endometrial carcinomas may be an independent
      prognostic and/or predictive factor.

PMID- 15160342
TI  - Loss of heterozygosity on the X chromosome is an independent prognostic factor in
      ovarian carcinoma: from the Danish "MALOVA" Ovarian Carcinoma Study.
AB  - BACKGROUND: Ovarian carcinoma (OC) is the fifth most frequent female cancer type
      and the fourth most frequent cause of death from cancer among women in Denmark.
      At the time they are diagnosed with OC, approximately 70% of patients have
      advanced disease. It is believed that loss of tumor suppressor gene activity
      plays an important role in the origin and progression of OC and other
      malignancies. Loss of heterozygosity (LOH) may be detected in individuals
      heterozygous for an allele and is associated with loss of function of tumor
      suppressor genes. METHODS: The polymorphic marker regions (TP53, CACNLB1, D18S58,
      DXS538, and DXS454) were amplified by polymerase chain reaction followed by
      separation using gel electrophoresis before LOH was identified. In total, 160
      women with primary epithelial OC were included in the study. RESULTS: Univariate
      analyses showed significant differences in survival between patients who had
      advanced OC with LOH or with retention using the microsatellite markers DXS454 (P
      = 0.04) and DXS538 (P = 0.01). Multivariate Cox regression analysis that included
      all patients showed that DXS454 (relative hazard [RH] = 3.5; P = 0.002; 95%
      confidence interval [95% CI], 1.6-7.8), radicality of primary surgery (RH = 5.5;
      P < 0.0001; 95% CI, 2.7-11.1), and serum tetranectin level (RH = 0.8; P = 0.009;
      95% CI, 0.7-0.9) were independent prognostic factors for survival. Multivariate
      Cox regression analysis restricted to patients with International Federation of
      Obstetrics and Gynecology Stage III-IV disease showed that DXS454 (RH = 3.4; P =
      0.007; 95% CI, 1.4-8.1), radicality of primary surgery (RH = 5.4; P < 0.0001; 95%
      CI, 2.2-12.9), and serum tetranectin level (RH = 0.8; P = 0.042; 95% CI, 0.7-1.0)
      were independent prognostic factors. CONCLUSIONS: LOH at DXS454 (Xq21-q23)
      appeared to be correlated with reduced survival in patients with OC.

PMID- 15160344
TI  - High-dose intravenous methotrexate followed by autologous stem cell
      transplantation as a potentially effective therapy for neurolymphomatosis.
AB  - BACKGROUND: Neurolymphomatosis (NL) is a rare neurologic manifestation of
      systemic lymphoma characterized by lymphomatous infiltration of the peripheral
      nervous system. The diagnosis of NL is difficult and requires a multidisciplinary
      approach for obtaining an adequate biopsy specimen of the suspected nerve. The
      prognosis of patients with NL has been poor because adequate penetration of
      chemotherapy into the nervous system is difficult. METHODS: The authors presented
      the case of a 37-year-old man who was treated for Ann Arbor Stage IVB diffuse
      large B-cell lymphoma. The patient developed disease recurrence in the sciatic
      nerve without systemic involvement. RESULTS: The patient achieved a clinical
      response after receipt of high-dose intravenous methotrexate followed by high
      dose chemotherapy and autologous stem cell transplant. CONCLUSIONS: The authors
      reported this case to highlight the effectiveness of this regimen in a rare and
      fatal disorder. In the current study they also reviewed the literature regarding
      the diagnosis, prognosis, and treatment of NL.

PMID- 15160343
TI  - Erythropoietin is effective in improving the anemia induced by imatinib mesylate
      therapy in patients with chronic myeloid leukemia in chronic phase.
AB  - BACKGROUND: Myelosuppression occurs in up to 50% of patients with chronic myeloid
      leukemia (CML) who are treated with imatinib and > or = Grade 3 myelosuppression
      is reported in approximately 10% of patients. METHODS: The authors investigated
      the prognostic significance of anemia occurring during therapy with imatinib in
      patients with CML in chronic phase. RESULTS: Of 338 patients treated with
      imatinib (150 patients after interferon failure and 188 patients with newly
      diagnosed CML), 230 (68%) developed anemia. In a multivariate analysis, factors
      associated with an increased probability of developing anemia were a starting
      hemoglobin level < 12 g/dL, age > or = 60 years, female gender, higher imatinib
      dose, and intermediate or high Sokal risk group. Of these 230 patients, 102
      patients received treatment with 40,000 U of recombinant human erythropoietin
      administered subcutaneously once weekly. An increase in the hemoglobin level of >
      or = 2 g/dL was achieved in 69 patients (68%) and 22 patients (22%) had an
      increase of 1-1.9 g/dL. Patients who developed anemia had a trend toward a lower
      probability of complete cytogenetic remission compared with patients without
      anemia (68% vs. 77%; P = 0.14), as well as a trend for inferior survival.
      Patients with anemia and other manifestations of myelosuppression were found to
      have a significantly worse outcome than those with isolated anemia. CONCLUSIONS:
      The authors concluded that erythropoietin is safe and effective in patients in
      chronic-phase CML who develop anemia with imatinib therapy.

PMID- 15160345
TI  - Low-dose weekly paclitaxel for recurrent or refractory aggressive non-Hodgkin
      lymphoma.
AB  - BACKGROUND: Many patients with recurrent, intermediate or high-grade non-Hodgkin
      lymphoma (NHL) may not respond to or are not candidates for aggressive salvage
      chemotherapy. Effective, less toxic regimens are needed. Although high-dose
      taxanes have not been reported to be very effective for the treatment of
      lymphoma, different delivery rates may allow for different mechanisms of action
      to be manifest and result in a different toxicity profile and response rate. The
      current study tested this hypothesis by using low-dose, weekly paclitaxel in
      patients with recurrent or refractory NHL. METHODS: Adults age > 18 years with
      refractory or recurrent, aggressive NHL who were not considered curable with
      standard high-dose therapy received paclitaxel at a dose of 80 mg/m2 weekly for 5
      weeks for 2 cycles. RESULTS: Thirty-four patients with refractory NHL and 4
      patients with recurrent disease were treated. Approximately 45% of the patients
      had achieved a prior disease remission. The median number of prior regimens
      received was 3, 74% of the patients had an International Prognostic Index of > or
      = 3 at the time of study entry, and 29% had failed high-dose therapy with
      autologous hematopoietic support. Only one patient encountered severe toxicity
      (sepsis). Myelosuppression was reported to occur in approximately 20% of
      patients. A total of 10 patients (26%) achieved a complete disease response and 4
      patients (11%) achieved a partial response. CONCLUSIONS: In the current study,
      low-dose, weekly paclitaxel therapy was found to provide a well tolerated and
      less toxic approach to the treatment of refractory NHL, with encouraging
      responses noted in heavily pretreated patients. However, evaluation in patients
      with an earlier stage of disease is warranted.

PMID- 15160346
TI  - Changes in the characteristics and survival rate of hepatocellular carcinoma from
      1976 to 2000: analysis of 1365 patients in a single institution in Japan.
AB  - BACKGROUND: The authors analyzed changes in the characteristics and survival rate
      of patients with hepatocellular carcinoma (HCC) in the past 25 years. METHODS:
      Trends in clinical characteristics and survival rate of patients with HCC were
      evaluated retrospectively based on data from 1365 patients who were diagnosed,
      treated, and followed between 1976 and 2000. RESULTS: Between 1976-1995, the
      number of patients with smaller tumors, a less advanced tumor stage, and with a
      lower Child-Pugh class increased markedly. No differences were observed in the
      distributions of these three factors between the periods 1991-1995 and 1996-2000.
      The year of HCC diagnosis, tumor size, tumor stage, Child-Pugh class, and the
      kind of initial treatment received correlated significantly with patient survival
      rates by multivariate analysis. The year of HCC diagnosis was found to contribute
      independently to the improvement in patient survival rates. Using the Kaplan
      Meier comparison, the time periods during which the highest patient survival
      rates occurred were found to be 1991-1995/1996-2000, 1986-1990, and 1976-1985, in
      that order. The authors did not observe a difference with regard to survival
      rates between patients in the 1991-1995 and 1996-2000 groups. CONCLUSIONS: The
      characteristics of patients with HCC changed dramatically from 1976 to 1995 (but
      not in the past 10 years) toward the earlier detection of HCC. This contributed
      to the improvement noted in patient survival rates during this period. The year
      of HCC diagnosis was found to be an independent factor for the improved survival
      rates by multivariate analysis. This indicated that the progress of treatment and
      care for patients with HCC contributed to the annual improvement in patient
      survival rates.

PMID- 15160347
TI  - Radiotherapy combined with transarterial infusion chemotherapy and concurrent
      infusion of a vasoconstrictor agent for nonresectable advanced hepatic hilar duct
      carcinoma.
AB  - BACKGROUND: The treatment of patients with advanced hepatic hilar duct carcinoma
      is a challenging problem. The current study was performed to evaluate the outcome
      of patients with advanced hepatic hilar duct carcinoma who received external beam
      radiotherapy (EBRT) combined with transarterial chemotherapy and infusion of a
      vasoconstrictor. METHODS: Between April 1993 and December 2002, 23 patients with
      histopathologically confirmed hilar duct carcinoma entered the study. The median
      total dose of EBRT was 41.4 grays (Gy). Transarterial chemotherapy was performed
      twice during EBRT. It was comprised of an infusion of a cocktail of 20 mg of
      epirubicin, 10 mg of mitomycin C, and 500 mg of 5-fluorouracil and was
      administered 1 minute after injection of epinephrine via a catheter introduced in
      the hepatic arteries. After the combined treatment, the patients underwent
      biliary endoprosthesis after evaluation of the initial response to treatment by
      percutaneous transhepatic cholangiography (PTC). The initial responses based on
      PTC were classified into four categories: CR, no stenosis; PR, relief of
      stenosis/obstruction; NC, no change; and PD, progressive stenosis/obstruction.
      The outcome parameters were survival rates and time, as well as frequency and
      type of complications. RESULTS: Excluding 1 patient who discontinued the
      treatment, the initial responses of 22 patients were 1 CR (5%), 8 PR (36%), 11 NC
      (50%), and 2 PD (9%). The response rate was 41%. The overall survival rates at 1
      year, 2 years, and 3 years after treatment were 59%, 36%, and 18%, respectively.
      CONCLUSIONS: The combination of radiotherapy, transarterial infusion
      chemotherapy, and concurrent infusion of a vasoconstrictor can be delivered
      safely with good efficacy for patients with advanced hilar duct carcinoma.

PMID- 15160348
TI  - Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis
      through down-regulation of caspase-3 activity.
AB  - BACKGROUND: It is believed that midkine (MK), a heparin-binding growth factor,
      plays an important role in carcinogenesis. However, the biologic mechanism of MK
      in hepatocellular carcinoma has not been clarified to date. The objective of the
      current study was to investigate the antiapoptotic role of MK in a human hepatoma
      cell line. METHODS: The human hepatoma cell line HepG2 was used to study the
      antiapoptotic effect of MK. Tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL)/actinomycin D (ActD)-induced apoptosis was detected using a 2-(2
      methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphophenyl)-2H-tetrazolium
      monosodium salt (WST-8) assay, a caspase-3 activity assay, a caspase-8 activity
      assay, and flow cytometric analysis. RESULTS: TRAIL had a potent, dose-dependent
      inductive effect on cell death in HepG2 cells, for which viable cell counts
      decreased to 6.3% of the control count at a TRAIL concentration of 100 ng/mL in
      the presence of 500 ng/mL ActD. Flow cytometry was used to demonstrate that
      apoptosis induced by TRAIL/ActD was in fact the cause of cell death. According to
      the WST-8 assay, MK pretreatment resulted in the suppression of TRAIL/ActD
      mediated apoptosis in HepG2 cells, although cell viability did not increase when
      HepG2 cells were treated with MK alone. Caspase-3 activity was down-regulated
      when MK was added, but caspase-8 activity was high in both the absence and
      presence of MK. CONCLUSIONS: The results of the current study indicate that MK
      acts as an antiapoptotic factor in HepG2 cells through the down-regulation of
      caspase-3 activity.

PMID- 15160349
TI  - Weekly combination chemotherapy with docetaxel and gemcitabine as first-line
      treatment for elderly patients and patients with poor performance status who have
      extensive-stage small cell lung carcinoma: a Minnie Pearl Cancer Research Network
      phase II trial.
AB  - BACKGROUND: The goal of the current study was to evaluate the feasibility,
      toxicity, and efficacy of a novel combination of weekly docetaxel and gemcitabine
      for elderly patients and patients with poor performance status who had advanced
      stage small cell lung carcinoma (SCLC). METHODS: Previously untreated patients
      with advanced-stage SCLC were eligible for the current clinical trial. In
      addition, patients were required to be age > 65 years or to have poor performance
      status (Eastern Cooperative Oncology Group 2). All patients received 800 mg/m2
      gemcitabine and 30 mg/m2 docetaxel intravenously on Days 1, 8, and 15. Courses
      were repeated at 28-day intervals. RESULTS: Forty patients were enrolled in the
      current multicenter, community-based trial. Nine patients (23%) had partial
      responses to treatment. The median survival for the entire group was 4 months.
      Fourteen percent of patients were alive at 1 year. Myelosuppression was mild to
      moderate, with no episodes of neutropenia and fever. Grade 3/4 fatigue (25%) was
      the only common nonhematologic toxicity. CONCLUSIONS: Although relatively well
      tolerated, the weekly regimen of gemcitabine and docetaxel possessed only modest
      activity in this group of patients with unfavorable prognosis. The regimen
      offered no potential advantages over standard treatment approaches and is not
      recommended for further development.

PMID- 15160350
TI  - Therapy of meningeal melanocytomas.
AB  - BACKGROUND: Meningeal melanocytomas are rare, benign central nervous system
      lesions with a high probability of recurrence. To the authors' knowledge,
      approximately 100 cases have been reported since 1972, when the entity first was
      described. In the current study, four therapies were compared with regard to
      local control and survival to identify which is best. METHODS: All reported cases
      were reviewed with regard to extent of resection, radiotherapy, local control,
      and survival. If published data were incomplete, the authors were contacted for
      additional data. Patients were categorized by therapy: complete resection (CTR),
      complete resection followed by radiotherapy (CTR-RT), incomplete resection (ITR),
      and incomplete resection followed by radiotherapy (ITR-RT). Local control and
      survival were calculated using the Kaplan-Meier method. A multivariate analysis
      was performed including age, gender, tumor location, confirmation of extent of
      resection, and treatment schedule. RESULTS: A total of 89 patients were included:
      46 with CTR, 3 with CTR-RT, 23 with ITR, and 17 with ITR-RT. The 5-year local
      control rate was 80% after CTR, 100% after CTR-RT, and 72% after ITR-RT versus
      18% after ITR (P < 0.001). The 5-year survival rate was 100% after CTR, CTR-RT,
      and ITR-RT, respectively, versus 46% after ITR (P < 0.001). Multivariate analysis
      demonstrated that therapy was the only variable that affected local control and
      survival significantly. In 14 patients treated with ITR-RT, RT was restricted to
      the tumor region. The radiation dose was 30-40 grays (Gy) in 6 patients, 45-55 Gy
      in 7 patients, and unknown in 1 patient. The 5-year local control rate was 86%
      after a dose of 45-55 Gy versus 27% after a dose of 30-40 Gy (P = 0.1).
      CONCLUSIONS: CTR was found to be significantly superior to ITR with regard to
      both local control and survival. Outcome was significantly improved by RT after
      ITR. Doses of 45-55 Gy appeared to be more beneficial than doses of < or = 40 Gy.

PMID- 15160351
TI  - Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients
      treated at a single institution.
AB  - BACKGROUND: The objective of this study was to assess long-term prognosis and
      patterns of failure in patients with retroperitoneal soft tissue sarcoma who
      underwent surgery with curative intent at a single institution. Several series of
      patients with retroperitoneal sarcoma were reported, providing widely variable
      data regarding local and distant failure. METHODS: Overall, 167 consecutive
      patients who underwent surgery for retroperitoneal soft tissue sarcoma over a 20
      year span at a single referral center were reviewed retrospectively. Eighty-two
      patients presented with primary disease, whereas 85 patients had recurrent
      locoregional tumors. Surgical resection was considered macroscopically complete
      in 147 of 167 patients (88%). RESULTS: Overall survival at 10 years after
      definitive surgery was approximately 27%, and the disease-free survival was
      approximately 16%. Only a minority of patients developed distant metastases. The
      risk of recurrence was correlated with whether patients underwent surgery for
      primary disease or for recurrent disease; the 10 year disease-free survival rate
      was 27% in the former group and 4.6% in the latter group. Histotype and
      malignancy grade were other prognostic factors, with the former found to be
      predictive of the pattern of failure and the latter predictive of overall
      survival. CONCLUSIONS: Local recurrence after primary surgery and high-grade
      malignancy were associated with the worst survival. Histologic subtype appeared
      to influence the pattern of recurrence, which mainly was local for patients with
      liposarcoma but was both local and distant for patients with the other
      histotypes.

PMID- 15160352
TI  - Clinical significance of non-Candida fungal blood isolation in patients
      undergoing high-risk allogeneic hematopoietic stem cell transplantation (1993
      2001).
AB  - BACKGROUND: The clinical relevance of mold isolated from blood cultures, even in
      severely immunosuppressed allogeneic hematopoietic stem cell transplantation
      (HSCT) recipients, remains uncertain. The authors hypothesized that isolation of
      non-Candida fungi from blood cultures in patients undergoing high-risk HSCT would
      have clinical significance. METHODS: The authors reviewed the records of 73
      allogeneic HSCT recipients between January 1, 1993 and January 1, 2001 in whom
      fungal species were isolated from blood cultures. RESULTS: Fifty-two episodes of
      non-Candida fungemia occurred in 48 patients (66%) after a median of 10 days
      (range, 2-341) after transplantation. All 48 patients had indwelling
      intravascular catheters, and 23 patients (48%) had profound neutropenia. Thirty
      five of 48 patients had received partially matched, related donor stem cell
      grafts (19 patients had 3-antigen-mismatched grafts); 35 patients had undergone T
      cell depleted transplantation and 9 patients were receiving treatment for acute
      graft-versus-host disease. In 5 of 48 patients (10%), death was attributed to
      fungemia that occurred 8-11 days after the initial fungal blood culture was
      obtained; all 5 patients were age > 30 years. No deaths occurred in the younger
      age group (n = 22 patients; P = 0.05). In the 24 patients who did not receive
      systemic antifungal therapy, 4 deaths (17%) were attributed to infections with
      Penicillium (n = 2 patients), Epicoccum (n = 1 patient), or Penicillium plus
      Cladosporium species (n = 1 patient). Of the 24 patients who received
      amphotericin B, only 1 patient (4%) died as a result of a probable hematogenous
      Aspergillus species infection; this difference in outcome, however, was not
      significant (P = 0.2). CONCLUSIONS: Most of the non-Candida fungal blood culture
      isolates in recipients of high-risk, mismatched donor transplantation were
      clinically nonsignificant. However, because these low-virulence saprophytes
      occasionally may cause life-threatening disease, a reevaluation of the existing
      diagnostic paradigm is needed so that clinically significant fungemia may be
      differentiated from pseudofungemia.

PMID- 15160354
TI  - Pathologic evaluation of radical cystectomy specimens: a cooperative group
      report.
AB  - BACKGROUND: The authors evaluated the pathology of radical cystectomy and pelvic
      lymph node specimens from patients with bladder carcinoma who were enrolled in a
      cooperative group trial. Their objective was to determine whether current
      practices conform to suggested pathology practice guidelines for reporting on
      radical cystectomy and pelvic lymph node specimens. METHODS: Overall, 268
      patients underwent radical cystectomy with pelvic lymph node dissection over 11
      years in a total of 109 diverse geographic locations and types of institutions.
      Institutions included 50 community hospitals, 36 academic hospitals, and 23
      Veterans Administration (VA)/military hospitals, which evaluated 84, 137, and 47
      patients, respectively. The quality of pathology examination was assessed based
      on the original pathology reports of specimens that were submitted according to
      published practice guidelines. RESULTS: Among all types of institutions,
      pathologic evaluation of radical cystectomy specimens generally was complete for
      tumor histology, grade, size, location, pathologic stage, lymph node status,
      prostate involvement, and associated mucosal abnormalities, including ureters and
      urethra. Perivesical fat (soft tissue) margins were not recorded in 10% of
      specimens, and 18% of patients did not mention either the presence or the number
      of lymph nodes. These deficiencies were observed primarily at community and VA
      hospitals. CONCLUSIONS: The overall quality of pathologic examination of radical
      cystectomy specimens is high. Better reporting of soft tissue margin status and
      pelvic lymph node counts is needed to achieve compliance with the standards
      published by evolving practice protocols. Standardized pathologic evaluation and
      reporting of radical cystectomy specimens will optimize important prognostic
      information and foster better communication between the pathologist, surgeon, and
      interested oncologists to benefit patients.

PMID- 15160355
TI  - Use of information resources by patients with cancer and their companions.
AB  - BACKGROUND: Use of the Internet is common among patients with cancer and their
      companions. However, little is known about patterns of use of print or telephone
      based resources amidst growing Internet utilization, nor is it known whether
      different types of information are sought from electronic compared with print
      media. It is not clear as to whether patients and their companions differ in
      their patterns of content seeking. METHODS: A survey was developed to evaluate
      the use of electronic and nonelectronic informational resources by patients and
      their companions. During a 10-week period, this questionnaire was administered to
      443 outpatients and 124 paired companions attending an urban academic cancer
      center. RESULTS: In this cohort, 64% of patients and 76% of companions were
      computer owners, with home Internet access indicated by 58% and 68%,
      respectively. Use of the Internet to obtain cancer-related information was
      reported by 44% of patients and 60% of companions. Print resources were used by
      79% of patients and 83% of companions, with telephone resources used by 22% and
      23%, respectively. The majority of Internet users also read print content (85%),
      whereas one-half of print users did not access data electronically (52%). Topic
      areas sought via print and the Internet were similar, with the exception of
      nutrition-related information, which was more commonly sought in print texts.
      There was a high rate of concordance between patient and companion use of both
      electronic and nonelectronic resources. CONCLUSIONS: Despite recent publicity and
      scrutiny focusing on the quality of Internet health care content, print products
      remain the most common source of information sought by patients with cancer.
      Future investigation should focus on the quality of print products used by
      patients.

PMID- 15160353
TI  - Assessment of procalcitonin as a diagnostic and prognostic marker in patients
      with solid tumors and febrile neutropenia.
AB  - BACKGROUND: Cancer patients with fever and neutropenia currently are assessed on
      clinical grounds only. The current study prospectively evaluated the efficacy of
      baseline procalcitonin (PCT) in the detection of bacteremia and in the prediction
      of outcome in patients with solid tumors and febrile neutropenia. METHODS: PCT
      levels were determined at baseline and every 48 hours in 104 patients undergoing
      chemotherapy who developed fever (axillary temperature > 38 degrees C on 2
      occasions or > 38.3 degrees C in a single record) and neutropenia (absolute
      neutrophil count < 500 cells/microL). RESULTS: The median baseline PCT values
      were significantly higher in patients who had microbiologically documented
      infections (1.24 ng/mL) compared with patients who had clinically documented
      infections (0.27 ng/mL) or fever of unknown origin (0.21 ng/mL; P < 0.01).
      Accordingly, a PCT cut-off value of 0.5 ng/mL was reached more frequently in
      patients who had microbiologically documented infections compared with patients
      who had clinically documented infections or fever of unknown origin (66.7% vs.
      13.4%, respectively; P < 0.001). Furthermore, this threshold also was associated
      with an increased likelihood of treatment failure (70.0% vs. 14.9%; P < 0.001).
      All 4 septic patients and all 5 patients who ultimately died presented PCT values
      5-fold to 10-fold greater than the median values. Clinical evaluation in
      combination with baseline PCT assessment appeared to improve clinical risk
      evaluation alone. CONCLUSIONS: Baseline PCT levels were higher in patients who
      had febrile neutropenia with bacteremia compared with patients who had clinical
      infections or fever of unknown origin. PCT helped to identify patients who had
      microbiologic infections and patients who were at high risk of treatment failure,
      and PCT may constitute a complementary tool in the initial assessment of such
      patients.

PMID- 15160357
TI  - Cancer-related fatigue: evolving concepts in evaluation and treatment.

PMID- 15160358
TI  - Mismatch repair gene expression defects contribute to microsatellite instability
      in ovarian carcinoma.

PMID- 15160360
TI  - Imatinib mesylate causes hypopigmentation in the skin.

PMID- 15160362
TI  - Multifocal/multicentric breast carcinoma.

PMID- 15160364
TI  - Earliest Miocene hominoid from Southeast Asia.
AB  - A new hominoid fossil site, Chiang Muan in northern Thailand, yielded the first
      finding of a large-bodied Miocene hominoid in Southeast Asia. This specimen (CMu6
      1'00) was preliminarily reported by Kunimatsu et al. Later, Chaimanee et al.
      reported additional hominoid teeth from the same site, but all of them were
      collected from younger deposits (the Upper Lignite Member, in Nagaoka and
      Suganuma). The specimen described here (CMu6-1'00) was recovered from the Lower
      Lignite Member (Nagaoka and Suganuma), which is probably several hundred thousand
      years older than the Upper Lignite Member (Suganuma et al.). This article
      provides a detailed description of this hominoid specimen and
      paleontological/geological data of the fossil site at Chiang Muan. The hominoid
      specimen (CMu6-1'00) is an isolated upper molar (right M1 or M2), similar in size
      to modern orangutans (Pongo pygmaeus). This upper molar has low and voluminous
      cusps, relatively thick enamel, and relatively low relief of the dentine/enamel
      junction, with only a faint remnant of the lingual cingulum. The age of Chiang
      Muan is estimated to be the latest Middle Miocene (ca. 11-12 Ma), based on the
      mammalian fossils (Nakaya et al.) and paleomagnetic study (Suganuma et al.). This
      suggests that the Chiang Muan Hominoid in the present study is an earlier member
      of Eastern Eurasian Miocene hominoids.

PMID- 15160365
TI  - Brain size and encephalization in early to Mid-Pleistocene Homo.
AB  - Important changes in the brain have occurred during the course of human
      evolution. Both absolute and relative size increases can be documented for
      species of Homo, culminating in the appearance of modern humans. One species that
      is particularly well-represented by fossil crania is Homo erectus. The mean
      capacity for 30 individuals is 973 cm(3). Within this group there is substantial
      variation, but brain size increases slightly in specimens from later time
      periods. Other Middle Pleistocene crania differ from those of Homo erectus.
      Characters of the facial skeleton, vault, and cranial base suggest that fossils
      from sites such as Arago Cave in France, the Sima de los Huesos in Spain, Bodo in
      Ethiopia, Broken Hill in Zambia, and perhaps Dali in China belong to the taxon
      Homo heidelbergensis. Ten of these mid-Quaternary hominins have brains averaging
      1,206 cm(3) in volume, and many fall beyond the limits of size predicted for Homo
      erectus of equivalent age. When orbit height is used to construct an index of
      relative brain size, it is apparent that the (significant) increase in volume
      documented for the Middle Pleistocene individuals is not simply a consequence of
      larger body mass. Encephalization quotient values confirm this finding. These
      changes in absolute and relative brain size can be taken as further corroborative
      evidence for a speciation event, in which Homo erectus produced a daughter
      lineage. It is probable that Homo heidelbergensis originated in Africa or western
      Eurasia and then ranged widely across the Old World. Archaeological traces
      indicate that these populations differed in their technology and behavior from
      earlier hominins.

PMID- 15160366
TI  - Ontogenetic allometry, heterochrony, and interspecific differences in the skull
      of African apes, using tridimensional Procrustes analysis.
AB  - Ontogenetic studies of African ape skulls lead to an analysis of morphological
      differences in terms of allometry, heterochrony, and sexual dimorphism. The use
      of geometric morphometrics allows us 1) to define size and shape variations as
      independent factors (an essential but seldom respected condition for
      heterochrony), and 2) to calculate in percentage of shape changes and to
      graphically represent the parts of shape variation which are related to various
      biological phenomena: common allometry, intraspecific allometry, and allometric
      and nonallometric shape discrimination. Three tridimensional Procrustes analyses
      and the calculation of multivariate allometries, discriminant functions, and
      statistical tests are used to compare the skulls of 50 Pan troglodytes, and 50
      Gorilla gorilla of different dental stages. The results both complement and
      modify classical results obtained from similar material but with different
      methods. Size and Scaling in Primate Morphology, New York: Plenum, p. 175-205).
      As previously described by Shea, the common growth allometric pattern is very
      important (64% of total shape variation). It corresponds to a larger increase of
      facial volume than of neurocranial volume, a more obliquely oriented foramen
      magnum, and a noticeable reshaping of the nuchal region (higher inion). However,
      the heterochronic interpretation based on common allometry is rather different
      from Shea. Gorillas differ from chimpanzees not only with a larger magnitude of
      allometric change (rate peramorphosis), as is classically said, but also grow
      more in size than in shape (size acceleration). In other words, for a similar
      stage of growth, gorillas have the size and shape corresponding to older
      chimpanzees, and for a similar shape, gorillas have a larger size than
      chimpanzees. In contrast, sexual dimorphism actually corresponds to allometric
      changes only, as classically demonstrated (time hypermorphosis). Sexual
      dimorphism is here significant in adult gorillas alone, and solely in terms of
      allometry (size-related shape and size, given that sagittal and nuchal crests are
      not taken into account). The study also permits us to differentiate two different
      shape variations that are classically confused in ontogenetic studies: a very
      small part of allometric shape change which is specific to each species (1% of
      the total shape variation), and nonallometric species-specific traits independent
      of growth (8% of total shape change). When calculated in terms of intraspecific
      allometries (including common allometry and noncommon allometry), shape changes
      are more extensive in gorillas (36% of total shape change) than in chimpanzees
      (29% of total shape change). The allometric differences mainly concern the inion,
      which becomes higher; the position of the foramen magnum, more dorsally oriented;
      and the palate, more tilted in adult gorillas than in adult chimpanzees. In
      contrast, nonallometric species-specific traits in gorillas are the long and flat
      vault characterized by a prominent occipital region, the higher and displaced
      backward glabella, and the protrusive nose. Biomechanical schemes built from
      shape partition suggest that the increased out-of-plumb position of the head
      during growth is partially compensated in gorillas by a powerful nuchal
      musculature due to the peculiar shape of the occipital region.

PMID- 15160367
TI  - Forest use and activity patterns of Callimico goeldii in comparison to two
      sympatric tamarins, Saguinus fuscicollis and Saguinus labiatus.
AB  - Callimico goeldii, Saguinus fuscicollis, and S. labiatus are sympatric in
      northern Bolivia and differ from each other in patterns of spatial and structural
      use of their environment. C. goeldii has a home range five times larger than that
      of mixed-species troops of S. fuscicollis and S. labiatus. The larger overlapping
      home range of C. goeldii allows it to move among Saguinus troops, giving it
      access to a wide range of different microhabitats. All three species use the most
      common microhabitat in the area, primary forest with dense understory, more than
      any other microhabitat type. C. goeldii habitat use varies by season, with bamboo
      and Heliconia microhabitats used more during the dry season. Each species shows
      preferences for different height classes: C. goeldii is found almost exclusively
      in the understory, S. fuscicollis uses the understory and middle canopy, and S.
      labiatus is found mostly in the middle canopy. These height class preferences are
      reflected in each species' locomotor styles, with C. goeldii showing the highest
      rates of vertical clinging and leaping, and S. labiatus showing the highest rates
      of branch-to-branch leaping and quadrupedal movement. The results suggest that C.
      goeldii may be restricted to forests with dense understory and a mosaic of other
      microhabitats. Furthermore, C. goeldii does not appear to use its tegulae for
      large branch foraging, but rather for vertical clinging and leaping between small
      vertical supports.

PMID- 15160368
TI  - Demographic parameters and life history of chimpanzees at Bossou, Guinea.
AB  - Demographic parameters of wild chimpanzees at Bossou, Guinea, are presented and
      compared with those of other populations. The population size of Bossou
      chimpanzees has been stable over the last 26 years, except during two incidents
      of partial deforestation. The annual birth rate for a female (mean = 0.194, but
      0.165 when the infant survived more than 4 years) and interbirth interval are not
      much different from those of other study sites. The primiparous age of Bossou
      chimpanzees, however, is far younger (mean = 10.9 years) than for all other known
      wild chimpanzee populations. The infant and juvenile survival rate is also the
      highest (female = 0.64, male = 0.52 for the first 8 years). As a result, the
      lifetime reproductive success of Bossou chimpanzees is estimated to be highest
      among long-term study sites. The rate of disappearance from Bossou dramatically
      increases during the adolescent stage, and most young chimpanzees disappear
      before or around maturation. Probably because the environmental capacity for
      chimpanzees at Bossou is at its limit, many young independent males, as well as
      females, have to disperse, though others may die. For chimpanzee alpha males of
      other populations, mature males may be needed as collaborators to defend
      resources. In the case of Bossou, however, a lack of adjacent groups, conspecific
      competitors, predators, and perhaps medium-sized mammals as prey for group
      hunting may eliminate this need of the alpha male for other males. The reasons
      why all males of other chimpanzee populations persist in being philopatric for
      life and maintain kin-related male bonds differing from most mammal species,
      including humans, are discussed.

PMID- 15160370
TI  - Are adult physiques geometrically similar? The dangers of allometric scaling
      using body mass power laws.
AB  - Human physique classification by somatotype assumes that adult humans are
      geometric similar to each other. However, this assumption has yet to be
      adequately tested in athletic and nonexercising human populations. In this study,
      we assessed this assumption by comparing the mass exponents associated with girth
      measurements taken at 13 different sites throughout the body in 478 subjects (279
      athletic subjects, and 199 nonexercising controls). Corrected girths which
      account for subcutaneous adipose tissue at the upper arm, thigh, and calf sites,
      and which simulate muscle circumference, were also calculated. If subjects are
      geometrically similar to each other, girth exponents should be approximately
      proportional to M(1/3), where M is the subjects' body mass. This study confirms
      that human adult physiques are not geometrically similar to each other. In both
      athletic subjects and nonexercising controls, body circumferences/limb girths
      develop at a greater rate than that anticipated by geometric similarity in fleshy
      sites containing both muscle and fat (upper arms and legs), and less than
      anticipated in bony sites (head, wrists, and ankles). Interestingly, head girths
      appear to remain almost constant, irrespective of subjects' body size/mass. The
      results also suggest that thigh muscle girths of athletes and controls increase
      at a greater rate than that predicted by geometric similarity, proportional to
      body mass (M(0.439) and M(0.377), respectively). These systematic deviations from
      geometric similarity have serious implications for the allometric scaling of
      variables such as energy expenditure, oxygen uptake, anaerobic power, and
      thermodynamic or anthropometric studies involving individuals of differing size.

PMID- 15160369
TI  - Patterns of behavior across reproductive states of free-ranging female black
      handed spider monkeys (Ateles geoffroyi).
AB  - Reports on the behavior of spider monkeys (genus Ateles) describe a suite of 5-6
      behaviors that are indicative of an estrous female. This study presents hormonal
      data as an independent measure of reproductive state to determine if these
      behaviors are associated with any particular reproductive state or stage of the
      ovarian cycle. Fecal samples collected from 6 free-ranging female black-handed
      spider monkeys (Ateles geoffroyi) over the course of 11 months were assayed for
      estrogen (E1C) and progesterone (PdG) metabolites, using an enzyme immunoassay.
      Behavioral data collected from the same females were analyzed for patterns
      associated with different reproductive states. A more detailed analysis of
      behavioral data associated with reproductively cycling periods determined whether
      each behavior clustered with copulations or a particular phase in the ovarian
      cycle. Observations of place-sniffing were more frequent for 4 of 5 females when
      reproductively cycling. Of all copulations observed, 80% occurred when the female
      participant was reproductively cycling. In addition, the rates of self-clitoral
      hold and self-clitoral rub behaviors were significantly higher for 2 of 4 and 4
      of 5 of females, respectively, when reproductively cycling. No behavior
      consistently occurred in association with copulations or with any particular
      phase in the ovarian cycle. Results from this study suggest that the behaviors
      tested in this paper can provide some information regarding female spider monkey
      reproductive state (whether or not she is reproductively cycling), but that they
      are not indicators of estrus in female spider monkeys.

PMID- 15160371
TI  - The complete classification of flaps.
AB  - Whereas the permutations and combinations in our arsenal of free flaps continue
      to increase exponentially, the lack of a coherent nomenclature system has caused
      this often to appear as only a haphazard array of bewildering possibilities. A
      simplified nomenclature schema is essential to enhance the acceptance and
      universal application of, as well as accurately describe, many of these new flap
      options. A minor modification of prior anatomical systems that incorporates all
      possible distinguishing characteristics in describing any given flap is an
      intrinsic part of the system, but the primary focus in flap identification is
      centered around its vascular supply. Several examples are given to illustrate how
      the complete classification of every free flap can be possible in a reproducible
      and highly interpretable fashion.

PMID- 15160372
TI  - Growth factors and flap survival.
AB  - Growth factors are members of a large functional group of polypeptide regulatory
      molecules that influence the biological activities of responsive cells. In the
      last decade, the use of a variety of growth factors as therapeutic agents to
      improve wound healing and the viability of ischemic skin flaps has aroused
      considerable interest. Here, we review the literature concerning the regulation
      of growth factors in a flap, the role of angiogenesis in flap survival, the
      effect of growth factors on the metabolism of a flap, and angiogenesis in flap
      prefabrication and maturation. The potential application of growth factors in
      gene therapies is also reviewed.

PMID- 15160373
TI  - Gene therapy in flap survival.
AB  - Growth factors are members of a large functional group of polypeptide regulatory
      molecules that exert a powerful influence on all phases of wound healing and
      repair through interactions with specific cell surface receptors. The use of
      growth factors to improve wound healing and the viability of ischemic skin flaps
      has been well-documented throughout the last decade. In this article, we review
      the literature concerning the use gene therapy in flap survival, including the
      various methods employed to transplant plasmids or viruses capable of coding and
      producing growth factors in ischemic tissue.

PMID- 15160374
TI  - Clinical and ultrasound evaluation of donor site morbidity after tram-flap for
      breast reconstruction.
AB  - The TRAM-flap has become a well-established method for breast reconstruction.
      Even though the aesthetic result is superior to implant reconstruction, a main
      disadvantage is the potential risk to create weakness of the abdominal wall. For
      evaluation of abdominal wall function, an imaging method has to be used which is
      able to prove functional properties of the remaining muscle. This study was
      undertaken in order to verify if ultrasound imaging is a reasonable method to
      examine muscle movements after TRAM-flap procedures in addition to clinical
      examination. In 8 patients, a DIEP-flap, in 11 patients, a free TRAM-flap, and in
      3 patients, a pedicled TRAM-flap were used for breast reconstruction. Patients
      were examined 10-72 months (mean, 32 months) after surgery. Ultrasound imaging of
      the abdominal wall was performed in longitudinal as well as cross sections
      (multifrequent, 13 Mhz; Siemens Elegra, Erlangen, Germany). The diameter of the
      remaining muscle was measured 2 cm below the rib bow, at the level of the
      umbilicus, and at the level of the skin scar. The operated side was compared to
      the nonoperated contralateral side. In order to evaluate the contractility of the
      remaining rectus muscle, patients were invited to perform sit-ups during
      ultrasound monitoring of muscle movement. Clinically the functional testing was
      performed by the method of Janda (Muskelfunktionsdiagnostik, 2nd ed. Berlin: Volk
      und Gesundheit; 1986). The abdominal wall was inspected for bulging or hernia
      formation. Additionally, patients answered a six-scale self-designed
      questionnaire concerning the impairment of daily living and pain. Muscle
      contractility as well as muscle diameter were graded into four degrees from 0-3.
      The highest degree of 3 with normal muscle contractility and muscle diameter was
      found in 1 of 5 patients after DIEP-flap. Degree 2, with reduced muscle
      contractility and reduced muscle diameter, was found in 10 of 22 patients,
      especially after unilateral TRAM-flap. Degree 1, with no muscle contractility and
      remaining muscle, and degree 0, with scar tissue, were found in 11 patients.
      Impairment in daily-life activity was found in 10 patients, while 8 patients
      complained of pain. Muscle strength scored by the method of Janda
      (Muskelfunktionsdiagnostik, 2nd ed. Berlin: Volk- und Gesundheit; 1986) reached 4
      and 5 in 19 patients after all kinds of flap harvesting; 3 patients reached Janda
      2 and 3 after unilateral free TRAM or unilateral DIEP-flap. In one patient, a
      hernia was detected after unilateral DIEP-flap; 10 patients showed bulging of the
      abdominal wall. Functional testing of the abdominal wall by the method of Janda
      as well as CT-scans or MRI for evaluation of the remaining muscle is reported in
      the literature. As there is a need for cost reduction in medical treatment, we
      were looking for a more cost-effective evaluation method compared to CT-scan or
      MRI. Ultrasound imaging of the donor site after TRAM-flap harvesting in order to
      evaluate the remaining function of the rectus muscle is not yet reported in the
      literature. We consider ultrasound imaging to be superior to CT-scan or MRI in
      terms of functional evaluation and cost effectiveness.

PMID- 15160376
TI  - Primary nerve repair by muscle autografts prepared with local anesthetic.
AB  - We evaluated the usefulness of muscle autografts obtained immediately after graft
      preparation with lidocaine injections for primary nerve repair. The right sciatic
      nerve of adult Wistar rats was sectioned, and muscle grafts obtained 15 min or 24
      h after lidocaine injection were used to repair a gap 1.5 cm long. Axon and fiber
      diameters, as well as myelin thickness, decreased to similar extents for grafts
      of both time intervals. The G-ratios in the distal stumps of both groups were not
      different from controls, indicating that regenerated axons had a proper level of
      myelination. The ultrastructural appearance of the neuromuscular junctions was
      similar to that of normal samples. These results indicate that there are no
      restrictions to the use of a muscle graft for primary nerve repair, immediately
      after lidocaine injection, since the nerve regeneration was comparable to that
      observed with this type of graft used 24 h after being prepared.

PMID- 15160375
TI  - Oberlin's ulnar nerve transfer to the biceps motor nerve in obstetric brachial
      plexus palsy: indications, and good and bad results.
AB  - We present 7 children with obstetric brachial plexus palsy treated by
      transferring two motor fascicles out of the ulnar nerve to the biceps nerve.
      Three were male, and 4 were female. The left-side brachial plexus was affected in
      4 patients, and the right side in 3 patients. All children had vaginal delivery;
      two of them presented with shoulder dystocia. The average birth weight was 4300 g
      (range, 3620-5500 g). Average age at time of operation was 16 months (range, 11
      24 months). The indication for the operation was absent active elbow flexion with
      active shoulder abduction against gravity in 4 cases, and no biceps function and
      bad shoulder function in 3 cases. Oberlin's ulnar nerve transfer was done in 4
      cases without brachial plexus exploration in those children with good shoulder
      function, and exploration of the brachial plexus was performed in the other 3
      cases with bad shoulder function. The average follow-up was 19 months (range, 13
      30 months). Five children had biceps muscle >or=M(3) with active elbow flexion
      against gravity, and 2 children had biceps muscle <M(3). We recommend Oberlin's
      ulnar nerve transfer for upper-type obstetric brachial plexus palsy in 1). breech
      delivery with avulsion of C5 and C6 nerve roots,) late presentation with good
      recovery of shoulder function, and 3). neuroma-in-continuity of the upper trunk
      with intraoperative good nerve conduction for the shoulder muscles, the same as
      preoperative good shoulder function but with no biceps action.

PMID- 15160377
TI  - Lack of chlorpromazine effect on skeletal muscle metabolism after ischemia and a
      short reperfusion period.
AB  - The great resistance of muscle to ischemia was used to study blood flow-dependent
      phenomena produced by anesthetic drugs in this condition. A short reperfusion
      period was used in order to favor metabolic changes indicative of an effect of
      chlorpromazine (CPZ) on blood flow. Gracilis muscles of dogs were submitted to 5
      h of ischemia and 30 min of reperfusion. CPZ-treated animals were injected I.V.
      (2 mg/kg) 10 min before the beginning of ischemia. Biopsies provided the material
      for tissue measurements. Lactate content and pH were determined in blood samples
      collected from a muscle efferent vein. In both the CPZ-treated and nontreated
      groups, ischemia induced a decline in muscle glycogen content, with a
      corresponding increase in muscle lactate and a decrease in mitochondrial
      respiratory control ratio. After 30 min of reperfusion, tissue levels of lactate
      did not attain preischemic values but showed a clear decline in the two
      experimental groups, evidencing the reversible state of the muscle. All other
      metabolic parameters remained unchanged. Mitochondrial respiratory control
      remained functional during ischemia and reperfusion. Blood pH displayed similar
      changes in both groups. There was no metabolic indication that the drug affected
      blood flow during early reperfusion and/or of a greater sensitivity of muscle
      endothelial cells to anesthetic drugs.

PMID- 15160378
TI  - Composite vascularized skin/bone graft model: a viable source for vascularized
      bone marrow transplantation.
AB  - In this study, we introduce a new model for vascularized skin and bone marrow
      transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic
      dissection studies were performed in 5 animals. In the experimental group, 10
      isograft transplantations were performed between Lewis rats. Combined groin skin
      and femoral bone flaps were transplanted based on the femoral artery and vein.
      Transplants were evaluated on a daily basis. All flaps survived without problems
      over 100 days posttransplant. The skin component remained pink and pliable, and
      grew new hair. Histological examination of the femoral bone (except the femoral
      head) revealed active hematopoiesis with a viable compact and cancellous bone
      components on day 100 posttransplant. This model can be applied to tolerance
      induction studies across the major Histocompatibility (MHC) barrier, where bone
      will serve as donor of stem and progenitor cells, and the skin flap will serve as
      a monitor of graft rejection.

PMID- 15160379
TI  - Distal nerve elongation vs nerve grafting in repairing segmental nerve defects in
      rabbits.
AB  - Segmental nerve defects have been repaired with nerve grafts. However,
      regenerating fibers must go through two coaptation sites, and donor site
      morbidities are inevitable. We elongated the distal nerve segment using a tissue
      expander and reconnected the nerve. We compared these results with those of nerve
      grafting. Nerve injury models were created in the median nerves of both forelimbs
      in 27 rabbits. The right nerve was repaired by elongation, and the left by tibial
      nerve grafting. The length of the elongation was the same as that of the graft in
      each animal. Eight rabbits had a 10-mm segment repaired, 9 had a 15-mm segment
      repaired, and 10 had a 20-mm segment repaired. Evaluated outcomes were nerve
      conduction velocity, contractile force of the flexor muscle, axons number, and
      fiber diameter. The elongated and grafted groups did not differ substantially on
      any outcome. Distal nerve elongation could be an alternative to nerve grafting
      for repairing large nerve defects.

PMID- 15160381
TI  - Interactive advanced-communication multistation system for microsurgical
      training.
AB  - The use of cameras in microscopes is not in itself new; however, this paper
      describes a new use of microscope-mounted cameras in conjunction with an audio
      intercom system for training in microsurgical techniques. The application of new
      technology may enhance traditional microsurgical training. Our objective was to
      compare the opinions of students attending training courses before and
      implementation of an interactive training system. This qualitative, descriptive
      study analyzed the results of end-of-course satisfaction surveys carried out
      among 400 students (physicians and veterinarians), 240 before and 160 after
      implementation of the system. Compared to the conventional system used previously
      at the Minimally Invasive Surgery Center and still in use elsewhere, most
      students felt that monitoring, training, and troubleshooting were both easier and
      more thorough using the multistation system. The "multistation system" allows
      real-time, one-to-one, tutor-student interaction, obviating the need for the
      tutor to move from student to student, and allowing him to monitor activity at
      the same working magnification as the student. As a result, the level of student
      satisfaction has improved.

PMID- 15160380
TI  - Proximal nerve elongation vs nerve grafting in repairing segmental nerve defects
      in rabbits.
AB  - If segmental nerve defects could be repaired by elongating the proximal or distal
      segments, nerve grafting might be unnecessary. We elongated a 40-mm proximal
      segment of an injured median nerve, in the rabbit right forelimb, at a rate of 1
      mm/day for 10 days in 10 rabbits and for 15 days in another 10. On the left
      forelimb of the same rabbits, a 10- for 15-mm segment of the median nerve was
      removed, and a 10- for 15-mm segment, respectively, of the tibial nerve was
      grafted in its place. Four months after the initial surgery, nerve conduction
      velocity (NCV), contractile strength of the flexor digitorum superficialis (FDS),
      axon count, and axon diameter did not differ significantly between the 10-mm
      groups but were better in the 15-mm grafted group. Elongating the proximal nerve
      segment may be an alternative to grafting in repairing segmental defects of less
      than 10 mm.

PMID- 15160383
TI  - Phrenic nerve transfer in the treatment of brachial plexus avulsion: an
      experimental study of nerve regeneration and muscle morphology in rats.
AB  - The regeneration of motor and sensory neurons and the morphological changes of
      the target muscle after phrenic nerve transfer were investigated in adult rats.
      Six months following nerve transfer, 326.0 +/- 16.31 phrenic motoneurons
      regenerated into musculocutaneous nerve, which is not different from the normal
      number of phrenic motoneurons. The regenerated motoneurons exhibited a 14%
      nonsignificant hypertrophy. Of the dorsal root ganglia (DRG) neurons, 255.8 +/-
      45.26 regenerated, which was significantly lower than the number of normal
      phrenic DRG neurons. The regenerated phrenic DRG neurons showed a 24% close-to
      significant atrophy. The target muscle fiber morphology changed considerably
      after reinnervation. The present results suggest that the phrenic nerve has very
      good regenerative ability in terms of its motoneurons and a relatively
      insufficient sensory neuronal regeneration.

PMID- 15160382
TI  - Glucose, lactate, and pyruvate response in an experimental model of microvascular
      flap ischemia and reperfusion: a microdialysis study.
AB  - Early diagnosis of postoperative perfusion failure is essential in microsurgical
      tissue transfer. In order to determine if microdialysis could be used in
      diagnosing flap ischemia, we tested this method in an experimental pig model.
      Sixty-six flaps (34 myocutaneous and 29 cutaneous) were created in 18
      anesthetized pigs. During the experiment, secondary ischemia was induced for 5 h
      by selective clamping of the artery (20 flaps) or vein (21 flaps). Glucose,
      lactate, and pyruvate concentrations were measured hourly from the muscular and
      dermal layers. We found that decreasing glucose levels and increasing lactate
      concentrations were associated with arterial and venous occlusions from the first
      hour of ischemia. In venous ischemia, lactate concentrations remained lower than
      those in arterial ischemia. The increase in lactate-to-pyruvate and lactate-to
      glucose ratios was related to ischemia and also discriminated arterial occlusion
      from venous occlusion. In conclusion, microdialysis can be used to facilitate
      early detection of ischemia.

PMID- 15160384
TI  - Experimental animal studies of clip-induced microvascular trauma.
AB  - This study was designed to evaluate microvascular clip potential for causing
      changes in vessel-wall tissue and the extent to which this potential is
      influenced by features of the clip. Light and scanning electron microscopy were
      used to examine vessel-wall changes after temporary clip occlusion. Vessel
      patency is shown to be influenced by anastomosis and clip site, changes in
      occlusion force due to material fatigue are described, and novel clip features to
      reduce vessel trauma are proposed. Evaluation of mechanical clip properties
      showed that material fatigue does not lead to relevant loss of precision in alpha
      type clips. While the modified clip designed to reduce trauma cannot abolish
      trauma altogether, it significantly reduces the associated changes and hence the
      risk of thrombosis. Arteries were more sensitive than veins to clip-induced
      trauma, with increased occlusion force producing more severe damage than
      increased clipping time. Maximal changes were seen in the tunica media. These
      results indicate the paramount importance of applying modest clip pressure
      commensurate with the requirements of microvascular Surgery.

PMID- 15160385
TI  - Development of donor-specific chimerism and tolerance in composite tissue
      allografts under alphabeta-T-cell receptor monoclonal antibody and cyclosporine a
      treatment protocols.
AB  - Recently, we induced donor-specific tolerance to rat hindlimb allografts under a
      35-day course of alphabeta-T-cell receptor monoclonal antibody (alphabeta-TCR
      mAb) and cyclosporine A (CsA). In this report, we investigated the role of
      shorter alphabeta-TCR/CsA protocols on tolerance induction. We performed 52
      hindlimb transplantations, between Lewis-Brown-Norway (LBN, F1) donors and Lewis
      recipients to test the impact of 21-, 7-, and 5-day protocols of combined
      alphabeta-TCR/CsA treatment on tolerance induction. Donor-specific tolerance and
      immunocompetence were tested by mixed lymphocyte reaction (MLR) in vitro and by
      standard skin grafting in vivo. The efficacy of immunosuppressive protocol and
      donor-specific chimerism was assessed by flow cytometry. All transplants under 5,
      7, and 21 days of combined alphabeta-TCR/CsA therapy survived over 350 days.
      Clinical tolerance and immunocompetence were confirmed by skin grafting in vivo
      and MLR in vitro. Flow cytometry revealed a high level of donor chimerism in the
      peripheral blood of long-term survivors. The extension of survival of limb
      allografts and allo-unresponsiveness were directly associated with the
      development of stable chimerism in the tolerant recipients.

PMID- 15160386
TI  - Effect of hyperbaric oxygen therapy on nerve regeneration in early diabetes.
AB  - Nerve regeneration in diabetes is essential for reversal of neuropathy as well as
      the recovery of nerves from injury due to acute nerve compression and entrapment.
      Endoneural hypoxia due to hyperglycemia-induced blood flow reductions is observed
      early in the course of diabetes, and the resultant ischemia plays a role in the
      diminished neural regeneration. Hyperbaric oxygen therapy is capable of producing
      tissue hyperoxia by raising oxygen tensions in ischemic tissues, and was shown to
      be beneficial in the reversal of experimental ischemic neuropathy. In this study,
      an experimental diabetes model was used to evaluate the functional and
      histomorphological effects of hyperbaric oxygen therapy on early diabetic nerve
      regeneration. Our results indicate that there is significant histomorphological
      impairment of nerve regeneration, even in very early stages of diabetes. However,
      no beneficial effects of hyperbaric oxygen therapy could be demonstrated at this
      stage.

PMID- 15160387
TI  - It's "juxta" potassium channel!
AB  - Neuronal excitability depends on the appropriate expression and localization of
      ion channels. Juxtaparanodal Kv1 channels have been used as a model to study the
      role of neuroglial interactions in regulating the expression and localization of
      channels in myelinated axons. Recent advances in our understanding of the
      composition of juxtaparanodal Kv1 channel protein complexes as well as the
      cellular and molecular mechanisms underlying their localization at juxtaparanodes
      are discussed.

PMID- 15160389
TI  - Alpha-dystroglycan interactions affect cerebellar granule neuron migration.
AB  - The interaction of alpha-dystroglycan (a-DG) with its extracellular binding
      partners requires glycans attached to its mucin core domain, and defects in the
      glycosylation of a-DG are associated with both muscular dystrophy and neuronal
      migration defects. The involvement of a-DG and one of its ligands, agrin, in
      cerebellar neuronal migration was investigated. Antibodies directed against
      glycosylated a-DG inhibited granule neuron migration in cerebellar slice
      cultures. a-DG interactions did not appear to influence neurite outgrowth in
      cerebellar explant cultures, but enhanced granule neuron binding was observed on
      cells transfected with a-DG. These results suggest that interactions involving a
      DG influence the strength of attachment of granule neurons to the a-DG-expressing
      Bergmann glial cells that guide granule neuron migration in the cerebellum.
      Experiments using anti-agrin antibodies suggest that agrin is not involved in
      these interactions.

PMID- 15160388
TI  - Vesicle transport in oligodendrocytes: probable role of Rab40c protein.
AB  - Intracellular membrane trafficking plays an essential role in the structural and
      functional organization of oligodendrocytes, which synthesize a large amount of
      membrane to form myelin. Rab proteins are key components in intracellular
      vesicular transport. We cloned a novel Rab protein from an oligodendrocyte cDNA
      library, designating it Rab40c because of its homology with Rab40a and Rab40b.
      The DNA sequence of Rab40c shows an 843-base pair open reading frame. The deduced
      amino acid sequence is a protein with 281 amino acids, with a molecular weight of
      31,466 Da and an isoelectric point of 9.83. Rab40c presents a number of distinct
      structural features including a carboxyl terminal extension and amino acid
      substitutions in the consensus sequence of the GTP-binding motifs. The carboxyl
      terminal region contains motifs that permit isoprenylation and palmitoylation.
      Binding studies indicate that Rab40c binds guanosine 5'-0-(3-thiotriphosphate)
      (GTP gamma S) with a K(d) of 21 microM and has a higher affinity for guanosine
      triphosphate (GTP) than for guanosine diphosphate (GDP). Rab40c is localized in
      the perinuclear recycling compartment, suggesting its involvement in endocytic
      events such as receptor recycling. The importance of this recycling in myelin
      formation is suggested by the increase in both Rab40c mRNA and Rab40c protein as
      oligodendrocytes differentiate.

PMID- 15160390
TI  - Chronic morphine induces premature mitosis of proliferating cells in the adult
      mouse subgranular zone.
AB  - The birth of cells with neurogenic potential in the adult brain is assessed
      commonly by detection of exogenous S phase markers, such as bromodeoxyuridine
      (BrdU). Analysis of other phases of the cell cycle, however, can provide insight
      into how external factors, such as opiates, influence the cycling of newly born
      cells. To this end, we examined the expression of two endogenous cell cycle
      markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and
      phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU
      injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar
      distribution in the adult mouse subgranular zone (SGZ). Quantitative analysis
      within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU >>
      pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased
      BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show
      that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58%
      decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU
      IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature
      mitosis in chronic morphine-treated mice. These results suggest that morphine
      treated mice have a shorter Gap2/mitosis (G(2)/M) phase when compared to sham
      treated mice. These findings demonstrate the power of using a combination of
      exogenous and endogenous cell cycle markers and nuclear morphology to track
      proliferating cells through different phases of the cell cycle and to reveal the
      regulation of cell cycle phase by chronic morphine.

PMID- 15160391
TI  - Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and
      inhibits neurofilament axonal transport in response to oxidative stress.
AB  - Cyclin-dependent kinase 5 (cdk5) phosphorylates the high molecular weight
      neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport
      and induces perikaryal accumulation of disordered phospho-NF cables. Experimental
      and clinical motor neuron disease is characterized by oxidative stress, increased
      cdk5 activity, and accumulation of phospho-NFs within perikarya or proximal
      axons. Because oxidative stress increases cdk5 activity in experimental motor
      neuron disease, we examined whether oxidative stress induced cdk5-mediated NF
      phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide
      inhibited axonal transport of green fluorescent protein-tagged NF subunits and
      induced perikaryal accumulation of NF phosphoepitopes normally confined to axons.
      These effects were prevented by treatment with the cdk5 inhibitor roscovitine or
      transfection with a construct expressing the endogenous cdk5 inhibitor peptide.
      These findings indicate that oxidative stress can compromise NF dynamics via
      hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple
      aspects of neuropathology in motor neuron disease.

PMID- 15160392
TI  - Role of gamma-aminobutyric acid in early neuronal development: studies with an
      embryonic neuroectodermal stem cell clone.
AB  - gamma-Aminobutyric acid (GABA) has been known to function as an
      autocrine/paracrine signal molecule in addition to its well-known inhibitory
      neurotransmitter function. Studies on the developing brain and on primary brain
      cell cultures provided evidence for a variety of GABA functions in periods
      preceding the formation of synapses. The exact role of GABA in the early neural
      development, however, is still not well understood. In this study, one-cell
      derived NE-4C neuroectodermal stem cells were induced to form neurons and
      astrocytes in vitro, and the role of GABA was investigated in defined phases of
      neurogenesis. Noninduced NE-4C cells contained GABA, expressed GABA(A)R alpha
      subunits, and carried functional GABA(A) ion channels. A moderate cytoplasmic
      GABA content was detected during the entire period of differentiation. By the
      time of the formation of differentiated neurons, neuron-like cells with both high
      and low GABA content were clearly distinguishable. HPLC analysis indicated that
      NE-4C cells released GABA into their fluid environment during all stages of
      neuronal development. By using the patch-clamp technique, GABA-evoked currents
      were recorded during the entire proliferation/differentiation period, whereas a
      GABA-evoked increase in intracellular Ca(2+) was detected only during the
      maturation of postmitotic neuronal precursors. Bicuculline blocked both the ion
      currents and the [Ca(2+)](i) increase in response to GABA. Neuron formation was
      facilitated by GABA through GABA(A) ion channels during postmitotic
      differentiation, but not earlier during the phases of cell fate commitment.
      Although the data clearly demonstrate an early responsiveness to GABA,
      understanding the significance of GABA influence in early neural cell fate
      decisions will require further investigation.

PMID- 15160393
TI  - Neuronal NOS activation during oxygen and glucose deprivation triggers cerebellar
      granule cell death in the later reoxygenation phase.
AB  - The present study investigated the temporal relationship between neuronal nitric
      oxide synthase (nNOS) activity and expression and the development of neuronal
      damage occurring during anoxia and anoxia followed by reoxygenation. For this
      purpose, cerebellar granule cells were exposed to 2 hr of oxygen and glucose
      deprivation (OGD) and 24 hr of reoxygenation. To clarify the consequences of nNOS
      activity inhibition on neuronal survival, cerebellar granule cells were exposed
      to OGD, both in the absence of extracellular Na(+) ([Na(+)](e)), a condition that
      by reducing intracellular Ca(2+) ([Ca(2+)](I)) prevents Ca(2+)-dependent nNOS
      activation, and in the presence of selective and nonselective nNOS inhibitors,
      such as N(omega)-L-allyl-L-arginine (L-ALA), N(omega)-propyl-L-arginine (NPLA),
      and L-nitro-arginine-methyl-ester (L-NAME), respectively. The results
      demonstrated that the removal of [Na(+)](e) hampered the [Ca(2+)](i) increase and
      decreased expression and activity of nNOS. Similarly, the increase of free
      radical production present in cerebellar neurons, exposed previously to OGD and
      OGD/reoxygenation, was abolished completely in the absence of [Na(+)](e).
      Furthermore, the absence of [Na(+)](e) in cerebellar neurons exposed to 2 hr of
      OGD led to the improvement of mitochondrial activity and neuronal survival, both
      after the OGD phase and after 24 hr of reoxygenation. Finally, the exposure of
      cerebellar neurons to L-ALA (200 nM), and L-NAME (500 microM) was able to
      effectively reduce NO(*) production and caused an increase in mitochondrial
      oxidative activity and an improvement of neuronal survival not only during OGD,
      but also during reoxygenation. Similar results during OGD were obtained also with
      NPLA (5 nM), another selective nNOS inhibitor. These data suggest that the
      activation of nNOS is highly accountable for the neuronal damage occurring during
      the OGD and reoxygenation phases.

PMID- 15160394
TI  - Immunohistochemical localization of phosphorylated protein kinase R and
      phosphorylated eukaryotic initiation factor-2 alpha in the central nervous system
      of SJL mice with experimental allergic encephalomyelitis.
AB  - Inflammatory cells enter the CNS and target myelin in multiple sclerosis (MS) and
      experimental allergic encephalomyelitis (EAE), a model of MS, and inflammation is
      thought to induce stress responses in the CNS. Protein kinase R (PKR) and
      eukaryotic initiation factor-2 alpha (eIF2 alpha) undergo phosphorylation in
      response to stress, and the phosphorylated forms of these proteins play a key
      role in regulating protein synthesis. The objective of this study was to
      investigate the expression profile of phospho-PKR and phospho-eIF2 alpha during
      the course of EAE in order to advance the understanding of the stress response in
      this disease. In control animals (no encephalitogen with no emulsion; no
      encephalitogen with emulsion) and in preclinical EAE animals, phospho-PKR
      immunoreactivity was present in oligodendrocytes and some neurons, whereas, in
      EAE animals with active disease there was widespread labeling of inflammatory
      cells, and these cells were present during the recovery period of EAE, albeit to
      a lesser extent. Double-labeling studies revealed that T cells and a few
      macrophages were phospho-PKR(+). Phospho-eIF2 alpha immunoreactivity was detected
      in some oligodendrocytes in hindbrain sections of control animals. In EAE animals
      with active disease, the number of labeled oligodendrocytes increased, and
      inflammatory T cells also were labeled. Insofar as phospho-PKR activates nuclear
      factor-kappa B, it may facilitate cytokines expression by T cells. Alternatively,
      phospho-PKR and phospho-eIF2 alpha may promote apoptosis as a way to regulate T
      cell number in the CNS. The expression of phospho-eIF2 alpha in oligodendrocytes
      during EAE likely is involved with inhibition of protein translation, which is a
      protective mechanism used to promote cell survival in response to inflammation.

PMID- 15160395
TI  - Cytokine-induced cell death in human oligodendroglial cell lines: I. Synergistic
      effects of IFN-gamma and TNF-alpha on apoptosis.
AB  - Multiple sclerosis is a chronic inflammatory disease of the central nervous
      system. Myelin and oligodendrocytes are considered the major targets of injury
      caused by a cell-mediated immune response. There is circumstantial evidence that
      proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and
      interferon gamma (IFN-gamma) could have disease-promoting roles in multiple
      sclerosis (MS). In the present study, the cytotoxic effects of IFN-gamma and TNF
      alpha on the human oligodendroglial cell lines human oligodendroglioma (HOG) and
      MO3.13 were analyzed. When the oligodendroglial cell lines were cultured in the
      presence of IFN-gamma or TNF-alpha, apoptotic cell death was observed in both
      cell lines after >24 hr incubation. Apoptosis was evidenced by a decrease in cell
      viability, apoptotic changes in cell and nucleus morphology, and disruption of
      the membrane asymmetry. Our data show that TNF-alpha and IFN-gamma induce
      apoptosis in a dose-dependent fashion in both oligodendroglial cell lines and
      that their synergistic effect results in enhanced cell death. Understanding the
      regulation of cell death pathways in oligodendrocytes is critical for protecting
      myelin-producing cells and their associated axons during injury in patients with
      MS.

PMID- 15160397
TI  - Localization of wild-type and mutant neuronal ceroid lipofuscinosis CLN8 proteins
      in non-neuronal and neuronal cells.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are a group of childhood-onset
      neurodegenerative disorders characterized by accumulation of autofluorescent
      lipopigment in many tissues, especially in neurons. Mutations in the CLN8 gene
      underlie Northern epilepsy (progressive epilepsy with mental retardation [EPMR],
      OMIM 600143) and a subset of Turkish variant late infantile NCL, but the
      pathogenetic mechanisms have remained elusive. The CLN8 transmembrane protein is
      an endoplasmic reticulum (ER) resident protein that recycles between ER and ER
      Golgi intermediate compartment (ERGIC) in non-neuronal cells. To explore the
      disease mechanisms, we have characterized the neuronal localization of wild-type
      CLN8 protein as well as CLN8 proteins representing patient mutations. Semliki
      Forest virus-mediated CLN8 protein localized in the ER of mouse hippocampal
      primary neurons when compared to subcellular markers by immunofluorescence
      analysis. We also analyzed the possible polarized targeting of CLN8 and observed
      basolateral targeting in polarized epithelial CaCo-2 cells, suggesting that CLN8
      may locate outside the ER or in a specialized subcompartment of the ER. We were
      not able, however, to demonstrate differential distribution of CLN8 between axons
      and dendrites of neurons. Fractionation of mouse brain tissue indicated that
      endogenous mouse Cln8 is observed in light membrane fractions, different from ER,
      which further suggested differential localization for CLN8 in polarized cells.
      The disease mutations did not affect intracellular localization of CLN8 in non
      neuronal or neuronal cells. Consequently, there is no obvious genotype-phenotype
      correlation at the level of protein localization and thus mutations most likely
      directly affect functionally important domains of CLN8.

PMID- 15160396
TI  - Cytokine-induced cell death in human oligodendroglial cell lines. II: Alterations
      in gene expression induced by interferon-gamma and tumor necrosis factor-alpha.
AB  - Cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha), can initiate dual effects resulting in either cell growth or cell
      death. In this study, the human oligodendroglial cell lines HOG and MO3.13 were
      used as a model to study the molecular mechanisms of cytokine-induced cell death
      in human oligodendrocytes. We have previously shown that TNF-alpha and IFN-gamma
      induce apoptosis in both oligodendroglial cell lines within 72 hr. In the present
      study, the cell death pathways operating within these cells were further
      investigated at the gene expression level. Both cell lines express a broad
      repertoire of caspases and apoptosis-related genes. Some of these genes are
      specifically up-regulated by cytokine treatment; e.g., caspase-1 is up-regulated
      by IFN-gamma. In addition to direct cytotoxic effects, IFN-gamma and TNF-alpha
      also enhance the expression of Fas, TNFR1, and MHC class I molecules in both cell
      lines. This suggests that cytokines can make oligodendrocytes more vulnerable to
      different cell death pathways in an inflammatory environment. cDNA microarray
      analysis of the HOG cell line revealed that TNF-alpha induces genes that regulate
      apoptosis, survival, inflammation, cell metabolism, and cell signaling. The data
      suggest that oligodendroglial cells activate both death and survival pathways
      upon cytokine challenges. However, the survival pathways seem to be unable to
      compete with the death signal after more than 24 hr of cytokine treatment. These
      results may contribute to the development of therapeutic strategies aimed at
      interfering with cytokine-induced cell death of oligodendrocytes in patients with
      multiple sclerosis.

PMID- 15160398
TI  - Involvement of endoplasmic reticulum Ca2+ release through ryanodine and inositol
      1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid
      beta peptide.
AB  - Studies with in-vitro-cultured neurons treated with amyloid-beta (A beta)
      peptides demonstrated neuronal loss by apoptosis that is due, at least in part,
      to the perturbation of intracellular Ca(2+) homeostasis. In addition, it was
      shown that an endoplasmic reticulum (ER)-specific apoptotic pathway mediated by
      caspase-12, which is activated upon the perturbation of ER Ca(2+) homeostasis,
      may contribute to A beta toxicity. To elucidate the involvement of deregulation
      of ER Ca(2+) homeostasis in neuronal death induced by A beta peptides, we have
      performed a comparative study using the synthetic peptides A beta(25-35) or A
      beta(1-40) and thapsigargin, a selective inhibitor of Ca(2+) uptake into the ER.
      Incubation of cortical neurons with thapsigargin (2.5 microM) increased the
      intracellular Ca(2+) levels and activated caspase-3, leading to a significant
      increase in the number of apoptotic cells. Similarly, upon incubation of cortical
      cultures with the A beta peptides (A beta(25-35), 25 microM; A beta(1-40), 0.5
      microM), we observed a significant increase in [Ca(2+)](i), in caspase-3-like
      activity, and in number of neurons exhibiting apoptotic morphology. The role of
      ER Ca(2+) release through ryanodine receptors (RyR) or inositol 1,4,5
      trisphosphate receptors (IP(3)R) in A beta neurotoxicity has been also
      investigated. Dantrolene and xestospongin C, inhibitors of ER Ca(2+) release
      through RyR or IP(3)R, were able to prevent the increase in [Ca(2+)](i) and the
      activation of caspase-3 and to protect partially against apoptosis induced by
      treatment with A beta(25-35) or A beta(1-40). In conclusion, our results
      demonstrate that the release of Ca(2+) from the ER, mediated by both RyR and
      IP(3)R, is involved in A beta toxicity and can contribute, together with the
      activation of other intracellular neurotoxic mechanisms, to A beta-induced
      neuronal death. This study suggests that A beta accumulation may have a key role
      in the pathogenesis of AD as a result of deregulation of ER Ca(2+) homeostasis.

PMID- 15160399
TI  - Synaptosomal glutamate and GABA transport in patients with temporal lobe
      epilepsy.
AB  - High-affinity glutamate and GABA transporters found in the plasma membrane of
      neurons and glial cells terminate neurotransmission by rapidly removing
      extracellular transmitter. Impairment of transporter function has been implicated
      in the pathophysiologic mechanisms underlying epileptogenesis. We characterized
      glutamate and gamma-aminobutyric acid (GABA) transport in synaptosomes, isolated
      from neocortical and hippocampal biopsies of patients with temporal lobe epilepsy
      (TLE). We analyzed K(+)-evoked release in the presence and absence of Ca(2+) to
      determine vesicular and transporter-mediated release, respectively. We also
      analyzed (3)H-glutamate and (3)H-GABA uptake, the effect of glutamate uptake
      inhibitors L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and DL-threo-beta
      benzyloxyaspartate (TBOA), and GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)-3
      piperidinecarboxylic acid (SK&F 89976-A). Neocortical synaptosomes from TLE
      patients did not show vesicular glutamate release, strongly reduced transporter
      mediated release, and an increased basal release compared to that in rat
      synaptosomes. Furthermore, basal release was less sensitive to tPDC, and (3)H
      glutamate uptake was reduced compared to that in rat synaptosomes. Vesicular GABA
      release from neocortical synaptosomes of TLE patients was reduced compared to
      that in rat synaptosomes, whereas transporter-mediated release was hardly
      affected. Furthermore, basal GABA release was more than doubled, but neither
      basal nor stimulated release were increased by SK&F 89976-A, which did
      significantly increase both types of GABA release in rat synaptosomes. Finally,
      (3)H-GABA uptake by synaptosomes from TLE patients was reduced significantly in
      hippocampus (0.19 +/- 0.04%), compared to that in neocortex (0.32 +/- 0.04%).
      Control experiments with human peritumoral cortical tissue suggest that impaired
      uptake of glutamate, but not of GABA, was caused in part by the hypoxic state of
      the biopsy. Our findings provide evidence for impaired function of glutamate and
      GABA transporters in human TLE.

PMID- 15160400
TI  - Characteristics of the trigeminal depressor response in cats.
AB  - We studied the effects of electrical stimulation of the inferior alveolar nerve
      (IAN) on cardiovascular responses in cats. There was statistical correlation
      between cardiovascular response and prestimulus mean arterial blood pressure
      (MABP) and heart rate (HR). A trigeminal depressor response (TDR) was induced
      when the prestimulus MABP and HR were above 95 mm Hg and 140 beats/min,
      respectively. We investigated further to identify the vasomotor regulating center
      and neural transmitters involved in TDR. In the medulla, electrical stimulation
      of the dorsomedial medulla, the infratrigeminal nucleus (IFT), and the rostral
      ventrolateral medulla (RVLM) induced a vasopressor response. We confirmed that
      neurons in the RVLM were retrogradely labeled by wheat germ agglutinin-conjugated
      horseradish peroxidase injection into the nucleus intermediolateralis of the
      spinal cord. The vasopressor response induced by IFT stimulation was similar to
      that induced by IAN stimulation. Vasodepressor responses were induced when the
      caudal ventrolateral medulla, the nucleus tractus solitarius, the lateral
      tegmental field, the trigeminal nucleus interpolaris, the trigeminal spinal
      tract, and the paramedian reticular nucleus were stimulated. These responses,
      however, were not similar to the vasodepressor response induced by IAN
      stimulation but were similar to the cardiovascular response induced by vagal
      afferent stimulation. After spinalization or lesion of the RVLM, MABP and HR
      decreased and TDR completely disappeared. Inhibitory synaptic ligands and
      receptors were localized using immunohistochemical techniques. Neurons
      immunopositive for adrenaline, noradrenaline, and gamma-aminobutyric acid (GABA),
      and adrenaline alpha(2A), GABA(A), GABA(B), and glycine receptors were
      distributed along the sympatho-reflexive route including the RVLM and IFT. These
      results suggest that TDR could be induced as negative feedback to sympathetic
      hyperactivity whenever MABP and HR are high, because of the inhibitory control of
      the RVLM.

PMID- 15160401
TI  - Controlling the risk of spurious findings from meta-regression.
AB  - Meta-regression has become a commonly used tool for investigating whether study
      characteristics may explain heterogeneity of results among studies in a
      systematic review. However, such explorations of heterogeneity are prone to
      misleading false-positive results. It is unclear how many covariates can reliably
      be investigated, and how this might depend on the number of studies, the extent
      of the heterogeneity and the relative weights awarded to the different studies.
      Our objectives in this paper are two-fold. First, we use simulation to
      investigate the type I error rate of meta-regression in various situations.
      Second, we propose a permutation test approach for assessing the true statistical
      significance of an observed meta-regression finding. Standard meta-regression
      methods suffer from substantially inflated false-positive rates when
      heterogeneity is present, when there are few studies and when there are many
      covariates. These are typical of situations in which meta-regressions are
      routinely employed. We demonstrate in particular that fixed effect meta
      regression is likely to produce seriously misleading results in the presence of
      heterogeneity. The permutation test appropriately tempers the statistical
      significance of meta-regression findings. We recommend its use before a
      statistically significant relationship is claimed from a standard meta-regression
      analysis.

PMID- 15160402
TI  - Minimization of sample size when comparing two small probabilities in a non
      inferiority safety trial.
AB  - In clinical trials success rates of two treatments to be compared often range
      from 10 to 90 per cent. When the comparison probabilities are (much) smaller than
      10 per cent, standard methods for sample size and power calculations may provide
      invalid results. This situation may occur when there is interest in safety rather
      than in efficacy. In such trials, no more patients should be included than
      strictly necessary. We compared the results of maximum likelihood methods for the
      computation of sample sizes in a non-inferiority trial, including exact
      procedures and considered unequal sample sizes for experimental and reference
      treatment. An exact, unequal sample size maximum likelihood procedure is
      advocated when the specified non-zero risk difference under the null hypothesis
      is not too large. Such a procedure is also indicated when the parameter of
      interest is the relative risk, rather than the risk difference.

PMID- 15160403
TI  - Confidence intervals for the effect of a prognostic factor after selection of an
      'optimal' cutpoint.
AB  - When investigating the effects of potential prognostic or risk factors that have
      been measured on a quantitative scale, values of these factors are often
      categorized into two groups. Sometimes an 'optimal' cutpoint is chosen that gives
      the best separation in terms of a two-sample test statistic. It is well known
      that this approach leads to a serious inflation of the type I error and to an
      overestimation of the effect of the prognostic or risk factor in absolute terms.
      In this paper, we illustrate that the resulting confidence intervals are
      similarly affected. We show that the application of a shrinkage procedure to
      correct for bias, together with bootstrap resampling for estimating the variance,
      yields confidence intervals for the effect of a potential prognostic or risk
      factor with the desired coverage.

PMID- 15160404
TI  - Simultaneous inference for longitudinal data with detection limits and covariates
      measured with errors, with application to AIDS studies.
AB  - In AIDS studies such as HIV viral dynamics, statistical inference is often
      complicated because the viral load measurements may be subject to left censoring
      due to a detection limit and time-varying covariates such as CD4 counts may be
      measured with substantial errors. Mixed-effects models are often used to model
      the response and the covariate processes in these studies. We propose a unified
      approach which addresses the censoring and measurement errors simultaneously. We
      estimate the model parameters by a Monte-Carlo EM algorithm via the Gibbs
      sampler. A simulation study is conducted to compare the proposed method with the
      usual two-step method and a naive method. We find that the proposed method
      produces approximately unbiased estimates with more reliable standard errors. A
      real data set from an AIDS study is analysed using the proposed method.

PMID- 15160405
TI  - Cure fraction estimation from the mixture cure models for grouped survival data.
AB  - Mixture cure models are usually used to model failure time data with long-term
      survivors. These models have been applied to grouped survival data. The models
      provide simultaneous estimates of the proportion of the patients cured from
      disease and the distribution of the survival times for uncured patients (latency
      distribution). However, a crucial issue with mixture cure models is the
      identifiability of the cure fraction and parameters of kernel distribution. Cure
      fraction estimates can be quite sensitive to the choice of latency distributions
      and length of follow-up time. In this paper, sensitivity of parameter estimates
      under semi-parametric model and several most commonly used parametric models,
      namely lognormal, loglogistic, Weibull and generalized Gamma distributions, is
      explored. The cure fraction estimates from the model with generalized Gamma
      distribution is found to be quite robust. A simulation study was carried out to
      examine the effect of follow-up time and latency distribution specification on
      cure fraction estimation. The cure models with generalized Gamma latency
      distribution are applied to the population-based survival data for several cancer
      sites from the Surveillance, Epidemiology and End Results (SEER) Program. Several
      cautions on the general use of cure model are advised.

PMID- 15160406
TI  - A comparison of goodness of fit tests for age-related reference ranges.
AB  - Age-related reference ranges based on cubic spline or kernel-based smoothing
      methods lack a parametric framework with which to assess goodness of fit, as the
      distribution of the log-likelihood ratio comparing models with different degrees
      of smoothing is not known in general. Several methods have been proposed to
      assess goodness of fit in this case: Healy's grid test, Royston's Q tests and van
      Buuren's worm plot. Here we compare the performance of the various methods,
      including an extension of the Q tests, and show how they can be used, with other
      information including the appearance of the fitted curves, to inform the choice
      of model for age-related reference ranges of height and weight in a large Dutch
      data set.

PMID- 15160407
TI  - Gene expression profiling for prognosis using Cox regression.
AB  - Given the promise of rich biological information in microarray data we will
      expect an increasing demand for a robust, practical and well-tested methodology
      to provide patient prognosis based on gene expression data. In standard settings,
      with few clinical predictors, such a methodology has been provided by the Cox
      proportional hazard model, but no corresponding methodology is available to deal
      with the full set of genes in microarray data. Furthermore, we want the procedure
      to be able to deal with the general survival data that include censored
      information. Conceptually such a procedure can be constructed quite easily, but
      its implementation will never be straightforward due to computational problems.
      We have developed an approach that relies on an extension of the Cox proportional
      likelihood that allows random effects parameters. In this approach, we use the
      full set of genes in the analysis and deal with survival data in the most general
      way. We describe the development of the model and the steps in the
      implementation, including a fast computational formula based on a subsampling of
      the risk set and the singular value decomposition. Finally, we illustrate the
      methodology using a data set obtained from a cohort of breast cancer patients.

PMID- 15160408
TI  - A simple approach to power and sample size calculations in logistic regression
      and Cox regression models.
AB  - For a given regression problem it is possible to identify a suitably defined
      equivalent two-sample problem such that the power or sample size obtained for the
      two-sample problem also applies to the regression problem. For a standard linear
      regression model the equivalent two-sample problem is easily identified, but for
      generalized linear models and for Cox regression models the situation is more
      complicated. An approximately equivalent two-sample problem may, however, also be
      identified here. In particular, we show that for logistic regression and Cox
      regression models the equivalent two-sample problem is obtained by selecting two
      equally sized samples for which the parameters differ by a value equal to the
      slope times twice the standard deviation of the independent variable and further
      requiring that the overall expected number of events is unchanged. In a
      simulation study we examine the validity of this approach to power calculations
      in logistic regression and Cox regression models. Several different covariate
      distributions are considered for selected values of the overall response
      probability and a range of alternatives. For the Cox regression model we consider
      both constant and non-constant hazard rates. The results show that in general the
      approach is remarkably accurate even in relatively small samples. Some
      discrepancies are, however, found in small samples with few events and a highly
      skewed covariate distribution. Comparison with results based on alternative
      methods for logistic regression models with a single continuous covariate
      indicates that the proposed method is at least as good as its competitors. The
      method is easy to implement and therefore provides a simple way to extend the
      range of problems that can be covered by the usual formulas for power and sample
      size determination.

PMID- 15160409
TI  - Sample size determination for comparing several survival curves with unequal
      allocations.
AB  - Ahnn and Anderson derived sample size formulae for unstratified and stratified
      designs assuming equal allocation of subjects to three or more treatment groups.
      We generalize the sample size formulae to allow for unequal allocation. In
      addition, we define the overall probability of death to be equal to one minus the
      censored proportion for the stratified design. This definition also leads to a
      slightly different definition of the non-centrality parameter than that of Ahnn
      and Anderson for the stratified case. Assuming proportional hazards, sample sizes
      are determined for a prespecified power, significance level, hazard ratios,
      allocation of subjects to several treatment groups, and known censored
      proportion. In the proportional hazards setting, three cases are considered: (1)
      exponential failures--exponential censoring, (2) exponential failures--uniform
      censoring, and (3) Weibull failures (assuming same shape parameter for all
      groups)--uniform censoring. In all three cases of the unstratified case, it is
      assumed that the censoring distribution is the same for all of the treatment
      groups. For the stratified log-rank test, it is assumed the same censoring
      distribution across the treatment groups and the strata. Further, formulae have
      been developed to provide approximate powers for the test, based upon the first
      two or first four-moments of the asymptotic distribution. We observe the
      following two major findings based on the simulations. First, the simulated power
      of the log-rank test does not depend on the censoring mechanism. Second, for a
      significance level of 0.05 and power of 0.80, the required sample size n is
      independent of the censoring pattern. Moreover, there is very close agreement
      between the exact (asymptotic) and simulated powers when a sequence of
      alternatives is close to the null hypothesis. Two-moment and four-moment power
      series approximations also yield powers in close agreement with the exact
      (asymptotic) power. With unequal allocations, our simulations show that the
      empirical powers are consistently above the target value of prespecified power of
      0.80 when 50 per cent of the patients are allocated to the treatment group with
      the smallest hazard.

PMID- 15160411
TI  - A testing procedure for survival data with few responders.

PMID- 15160413
TI  - US government promises to fast-track AIDS drugs.

PMID- 15160414
TI  - Total knee replacement.

PMID- 15160415
TI  - PRONJ looks to reduce racial disparities in diabetes care.

PMID- 15160416
TI  - The marginal man revisited.

PMID- 15160417
TI  - Chasing the (MCP) codes.

PMID- 15160418
TI  - Moving toward a patient-centered payment system for ESRD beneficiaries.

PMID- 15160420
TI  - 15th annual PKD conference pursues "a capital quest for the cure".

PMID- 15160419
TI  - Transitioning to "the new way". A nephrologist's view.

PMID- 15160422
TI  - Multidisciplinary collaboration (MDC): what was it and where did it go?

PMID- 15160423
TI  - Endotoxin testing in the dialysis setting.

PMID- 15160421
TI  - Second phase of interim final regulations to Stark law clarifies issues for
      dialysis providers.

PMID- 15160424
TI  - Build new or refurbish? Important issues to consider in dialysis clinic
      construction.

PMID- 15160425
TI  - Connecting patients to the information highway. Bringing cyberspace to the
      dialysis clinic.

PMID- 15160426
TI  - Taking dialysis from in-center to home. Technical considerations.

PMID- 15160427
TI  - Issues for renal social workers in dialysis clinics in the United States. A
      survey/Part II.

PMID- 15160428
TI  - Dentists' wellness guide.

PMID- 15160429
TI  - Think you're covered if disability strikes--think again.

PMID- 15160430
TI  - Oral pathology quiz # 42. Case 1. Focal epithelial hyperplasia.

PMID- 15160431
TI  - Oral pathology quiz # 42. Case 2. Squamous cell papilloma.

PMID- 15160432
TI  - Oral pathology quiz # 42. Case 3. Odontogenic myxoma.

PMID- 15160433
TI  - Oral pathology quiz # 42. Case 4. Osteoporotic bone marrow defect.

PMID- 15160434
TI  - A conversation with Assemblyman Jefferson Van Drew, DMD. Interview by Eric R.
      Elmore.

PMID- 15160435
TI  - Kartagener's syndrome: a review of the literature and case report of oral
      findings in two siblings.

PMID- 15160436
TI  - Dental establishments in New Jersey.

PMID- 15160437
TI  - Use of CD63 expression as marker of in vitro basophil activation in identifying
      the culprit in insect venom allergy.
AB  - BACKGROUND: The diagnosis of insect venom allergy and the indication for specific
      immunotherapy is based on history, skin tests and demonstration of hymenoptera
      venom specific IgE-antibodies. In cases with contradictory test results
      additional cellular tests are recommended. OBJECTIVE: We evaluated the usefulness
      of a newly introduced test based on basophil CD63 expression as marker of
      activation in comparison with the basophil histamine release test (BHR) and the
      cellular antigen stimulation test (CAST) measuring leukotriene release. METHODS:
      In 14 patients (10 males, 4 females; age; 12 to 67 years, mean: 42.5 +/- 15.1
      years) with systemic reactions to hymenoptera stings in their history skin tests
      and determination of specific IgE-antibodies (CAP-RAST-FEIA) had shown
      inconsistent results: No demonstration of specific IgE-antibodies (n = 4), one
      sting by an unknown insect together with positive skin test and/or positive RAST
      to both bee and wasp venom (n = 4), several stings of partly unknown insects with
      positive skin test and/or demonstrable specific IgE-antibodies to more than one
      insect venom (n = 4), uncertain history and divergent results in skin test and/or
      RAST (n = 2). BHR, CAST and basophil activation test (BAT) were done according to
      the manufacturers with negative and positive controls and different
      concentrations of bee and wasp venom. The BAT is based on double staining with
      anti-IgE antibodies and anti-CD63 and subsequent determination of the percentage
      of activated basophils by flow cytometry. RESULTS: BAT and skin test were
      concordant in 42.9%, BAT and RAST in 57.1%. Concordance of all three cellular
      tests was seen in 57.1%, of BAT and BHR in 69.1%, of BAT and CAST in 78.6% and of
      BHR and CAST in 64.3%. In 6 cases where the three cellular tests (BHR, CAST, BAT)
      were not in accordance the addition of BAT led to a more reliable diagnostic
      result concerning the relevant insect in 3 cases and added no further information
      in 3 cases. BAT in controls always was negative. Correlation between CAST and BAT
      was higher than between CAST and BHR. CONCLUSIONS: In difficult cases of
      hymenoptera allergy, where history, skin tests and determination of specific
      antibodies do not allow a clear decision regarding the relevant insect species
      for immunotherapy, the additional performance of cellular tests (CAST and BAT)
      may be helpful.

PMID- 15160438
TI  - Tolerance and effects on skin reactivity to latex of sublingual rush
      immunotherapy with a latex extract.
AB  - BACKGROUND: Specific immunotherapy could be a therapeutic tool for the increasing
      problem of sensitisation to Natural Rubber Latex (NRL). OBJECTIVE: To investigate
      the tolerability of SLIT for Latex and its effects on skin reactivity. METHODS:
      Twenty-six patients (mean age 35.5 years) with an average history of 7.5 years of
      cutaneous symptoms plus respiratory symptoms (23/26) due to NRL were studied. All
      underwent rush sublingual therapy (4 days) with a standardized NRL extract
      followed by a 9-week maintenance treatment. Local and systemic adverse reactions
      were monitored throughout the treatment. Skin reactivity to NRL extract was
      evaluated before, during and at the end of the treatment by latex glove-use test,
      rubbing test and skin prick test. RESULTS: All patients reached the maintenance
      dose. Out of 1044 administered doses, 257 (24.6%) produced adverse reactions from
      which 21.4% were local. Only 10.1% of cases required treatment, mainly with
      antihistamines alone (5.8%), with 2-agonists alone (0.8%) or associated to
      antihistamines and/or corticosteroids (2.7%). One patient was precautionary
      treated twice with adrenaline but completed the treatment without further
      problems. The glove-use test improved significantly after 5 days and 10 weeks of
      treatment (p = 0.003, p = 0.0004 respectively), whereas the rubbing test improved
      significantly only after 10 weeks of treatment. Doctor's assessments confirmed
      the results obtained with the glove-use test (p = 0.003 after 5 days, and p =
      0.004 after 10 weeks) but not those obtained with the rubbing test. No change was
      detected for SPTs. CONCLUSION: SLIT for NRL allergy is able to modify skin
      reactivity to NRL in days as assessed with methods reproducing HCWs normal
      exposure to the allergen. Tolerance of SLIT is better than tolerance reported for
      injective therapy with NRL, but the build up phase should be administered under
      medical surveillance until sufficient experience has been accumulated. The long
      term effect of the treatment deserves further investigation.

PMID- 15160439
TI  - Suberosis and bird fancier's disease: a comparative study of radiological,
      functional and bronchoalveolar lavage profiles.
AB  - Hypersensitivity Pneumonitis (HP) is an immunologically mediated interstitial
      lung disease that may result from repeated inhalation of many different
      environmental agents. Heterogeneity of the clinical presentation and
      bronchoalveolar lavage profiles have been described, possibly related to
      different occupational exposures. The aim of our study was to compare
      bronchoalveolar lavage fluid (BALF), clinical, functional and radiological
      characteristics of the two most frequent forms of HP seen in our practice:
      Suberosis (an HP related to moldy cork dust exposure) and bird fancier's disease
      (BFD). We included 81 patients with Suberosis, with a mean age of 38.8 +/- 11.3
      years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a
      mean age of 46.3 +/- 11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients
      with BFD had more acute forms, while subacute and chronic presentations
      predominated in Suberosis. Restrictive defect was the most frequent pattern of
      lung function impairment, and more severe in BFD. Ground glass opacities were the
      most frequent pattern in high-resolution computed tomography. A normal chest x
      ray was more frequently seen in Suberosis. Both types of HP had lymphocytic
      alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 10(5) ml-l cells, 58.8 +/- 18.9%
      lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-l cells, 61.7 +/-
      22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases,
      the proportion of CD4+ and CD4/CD8 ratios were significantly higher in bird
      fancier's disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p < 0.005).
      Moreover, BALF cellularity and mast cell counts were also significantly higher in
      BFD. In conclusion, Suberosis and bird fancier's disease are HP with different
      clinical and laboratory profiles, suggesting that despite their
      pathophysiological similarities, different antigenic exposures may cause
      different immune and inflammatory response dynamics in the lung.

PMID- 15160440
TI  - A randomized, double-blind, parallel-group study, comparing the efficacy and
      safety of rupatadine (20 and 10 mg), a new PAF and H1 receptor-specific histamine
      antagonist, to loratadine 10 mg in the treatment of seasonal allergic rhinitis.
AB  - BACKGROUND: The main objective of this randomized, double-blind, parallel-group,
      comparative study was to assess the efficacy and safety of rupatadine 10 mg (R10)
      and 20 mg (R20) administered once-daily for two weeks compared with those of
      loratadine 10 mg (L10) in the treatment of seasonal allergic rhinitis (SAR).
      METHODS: A total of 339 SAR patients were randomized to receive R20 (111
      patients), R10 (112 patients) or L10 (116 patients). The main efficacy variable
      was the mean total daily symptom score (mTDSS) based on the daily subjective
      assessment of the severity of rhinitis symptoms--rhinorrhea, sneezing, nasal
      itching, nasal obstruction, conjunctival itching, tearing and pharyngeal itching-
      recorded by patients. RESULTS: The mTDSS was significantly lower in the groups
      treated with R20 (0.80 +/- 0.46) and R10 (0.85 +/- 0.52) than in the group
      treated with L10 (0.92 +/- 0.51) by protocol analysis (p = 0.03) but not by
      intention-to-treat analysis. The secondary variables used to assess efficacy
      (mDSS, DSSmax, CSS and TCSS) also showed significantly milder symptoms in
      patients treated with R20 and R10, particularly in sneezing and nasal itching.
      All treatments were well tolerated and no serious adverse events were recorded.
      Headache was the most frequent non-serious adverse event, and these did not show
      significant differences between treatments at similar dose levels. Somnolence was
      more frequent in R20 than in the other two groups. CONCLUSIONS: The present
      results suggest that rupatadine 10 mg a day may be a valuable and safe
      alternative for the symptomatic treatment of seasonal allergic rhinitis.

PMID- 15160441
TI  - PCR-based cloning and immunological characterization of Parietaria judaica pollen
      profilin.
AB  - Profilin has been described as an allergen present in pollen of trees, grasses
      and weeds. Since Parietaria judaica profilin has a molecular mass similar to
      other Parietaria allergens (Par j 1 and Par j 2) in the 14-10 kDa range, it is
      difficult to assess the prevalence of profilin by immunoblotting or to obtain
      sufficient amounts of purified native profilin for investigation and diagnosis.
      The aim of this study was to identify P. judaica profilin by PCR-based cDNA
      cloning and to elucidate its allergenic characteristics. Two cDNA clones encoding
      P. judaica pollen profilin were isolated by polymerase chain reaction (PCR)
      amplification using degenerate primers. Sequencing of both clones (Par j 3.0101
      and Par j 3.0102) demonstrated a high amino acid sequence homology.
      Immunodetection of P. judaica pollen after isoelectrofocusing and incubation with
      rabbit antiserum against profilin indicated the existence of at least 2 isoforms.
      Expression in Escherichia coli BL21 (DE3) was carried out using a vector based in
      the T7 expression system, and the recombinant allergen was isolated by affinity
      chromatography on poly-(L-proline)-Sepharose. Cross-reactivity has been found
      between recombinant P. judaica pollen profilin and profilins from other botanical
      unrelated plants.

PMID- 15160442
TI  - Skin test positivity to aeroallergens in the patients with chronic urticaria
      without allergic respiratory disease.
AB  - The etiology of chronic urticaria and angioedema remains uncertain in most of the
      patients. There are several agents and factors including medications, foods and
      food additives, infections, contactants, inhalants, physical factors and
      autoimmunity that implicated in provoking urticaria symptoms. In addition, the
      possible role of house dust mites has been considered in a few reports. We
      investigated skin test positivity to house dust mites and other inhalants in 259
      patients with chronic idiopathic urticaria and angioedema but without allergic
      rhinitis and/or asthma. Results were compared with both 300 healthy controls and
      300 atopic patients. Immediate cutaneous reactivity to one or more allergens was
      detected in 71 patients in the study group (27.4%). The most common allergens
      were house dust mites (24.7%). Skin prick test sensitivity to other inhalant
      allergens including pollens, molds and cockroach were 7.7%, 0.4% and 0.8%,
      respectively. In the healthy control group 7% of patients were found as atopic
      with respect to skin prick test results. The most common allergens in healthy
      controls were pollens (6%), and house dust mites (4.7%). In atopic control group,
      pollens and mites are also the most common allergens detected in skin prick test
      (62% and 50.3%, respectively). The difference between study and healthy control
      group was statistically significant with respect to presence of atopy and mite
      sensitivity (p < 0.001). Similar differences were not established in other
      inhalant allergens. Significant mite sensitivity in the study group is not a
      coincidence. Because, ratio of skin test positivity to house dust mites in the
      study group was higher than the healthy controls, but was not as high as atopic
      patients. Furthermore, the rate of skin reactivity to other aeroallergens was not
      different from healthy controls. Urticaria as a sole clinical manifestation in
      mite sensitive patients was unusual.

PMID- 15160444
TI  - Prevalence and risk factors for latex allergy: a cross sectional study on health
      care workers of an Italian hospital.
AB  - OBJECTIVES: The aim of this study was to determine prevalence and risk factors
      for latex hypersensitivity among health care workers (HCW) of an Italian general
      hospital. METHODS: 1747 HCW of the Ospedale Maggiore Policlinico of Milan were
      asked to fill in a questionnaire regarding latex-related manifestations (LRM) and
      personal medical history, and latex-specific IgE were measured by RAST-Cap
      system. RESULTS: 672 out of 1747 HCW (38.4%) answered to the questionnaire. LRM
      were reported by 168 out of 672 HCW (25%). The most common manifestation was hand
      dermatitis and itching (86.3%), followed by urticaria (3.5%) and respiratory
      symptoms (2.9%). Among the HCW with LRM, 75 (44.6%) reported a personal history
      of atopy and 24 (14.3%) reported oral allergy syndrome. most commonly related to
      kiwi, tomato, peach and melon/watermelon. Latex-specific IgE were found in 62 out
      of 1747 HCW (3.6%). Among the subjects answering the questionnaire, latex
      specific IgE positivity was associated with occurrence of LRM (most commonly
      allergic contact dermatitis) and a longer professional exposure. The risk of
      latex IgE sensitisation was four times higher in HCW reporting atopic
      manifestations than in HCW without atopic disorders. Prevalence of LRM and latex
      specific IgE was significantly higher among workers of auxiliary staff than among
      other job categories. The highest latex-specific IgE levels were found in
      subjects with severe latex-related symptoms and a personal history of atopy.
      CONCLUSIONS: A high prevalence of LRM was found among the HCW of an Italian
      general hospital, although a true latex sensitisation was detected only in a
      minority of cases. Members of the auxiliary staff, who wear latex gloves for
      several hours a day, had an increased prevalence of LRM and latex sensitisation.
      Atopy was a major risk factor for LRM and latex-specific IgE response.

PMID- 15160443
TI  - A randomized, double-blind, placebo-controlled study comparing the efficacy and
      safety of ebastine (20 mg and 10 mg) to loratadine 10 mg once daily in the
      treatment of seasonal allergic rhinitis.
AB  - Few randomized studies have compared the H1-receptor antagonists loratadine and
      ebastine in seasonal allergic rhinitis (SAR) patients. The objective of this
      study was to compare the efficacy and safety of ebastine 20 mg (E20), ebastine 10
      mg (E10), loratadine 10 mg (L10), and placebo (P), once daily, in controlling
      symptoms of SAR over a 4-week period. This was a double-blind, placebo
      controlled, randomized, parallel-group study. Efficacy was assessed in 749
      patients (12 to 70 years old) by SAR symptom scores (nasal discharge, congestion,
      itching, sneezing, and total eye symptoms) entered on diary cards every morning
      and every evening over the previous 12 hours (reflective score) and at the time
      of recording (snapshot score). The E20 group showed greater reductions from
      baseline compared with the L10 group in 2 daily reflective composite scores
      (nasal index [with or without congestion]) and in all 4 daily snapshot composite
      scores. E10 and L10 groups showed no significant differences in either the daily
      reflective or snapshot scores overall although E10 showed a greater improvement
      of nasal discharge snapshot score than L10. The efficacy of E20 at controlling
      the symptoms of SAR was well sustained during the fourth week of treatment, with
      significant differences over placebo in 22/36 total rhinitis symptom scores,
      followed by E10 (6/36), whereas L10 showed no differences (0/36). Patient and
      physician global evaluations at the final visit were not statistically
      significant for any treatment group compared with placebo. There was no
      significant difference among all groups in the number of patients who reported
      adverse events. In conclusion, ebastine 20 mg given once daily for 4 weeks in the
      treatment of SAR showed larger mean reductions from baseline in most rhinitis
      symptoms scores than loratadine 10 mg. Sustained efficacy was most frequently
      observed with ebastine 20 mg over placebo, whereas loratadine 10 mg did not
      provide a statistically significant improvement in any individual or composite
      symptom score at the end of the fourth week. Both ebastine 20 and 10 mg were well
      tolerated and proved safe in the treatment of SAR.

PMID- 15160446
TI  - IL-2 and IL-10 levels in induced sputum and serum samples of asthmatics.
AB  - BACKGROUND: There is consisting evidence that asthma is associated with airway
      inflammation. Originally IL-10 and IL-2 were described as lymphokines produced by
      T cells in mediating cellular infiltration into the airways and continue to be of
      interest in evaluating asthma pathogenesis. The aim of this study was to evaluate
      the serum and sputum levels of IL-2 and IL-10 in asthmatic subjects and healthy
      controls and to correlate disease activity and other clinical indices with
      concentrations of IL-2 and IL-10 in serum and sputum samples. METHODS: We
      evaluated cell profiles and IL-2 and IL-10 levels in induced sputum samples and
      in serum samples of 6 mild, 5 moderate, 7 severe asthmatic patients and 5 healthy
      controls by using ELISA. RESULTS: The mean IL-2 in sputum samples of asthmatics
      and controls were 35.3 +/- 13.2 pg/ml and 35.3 +/- 8.4 pg/ml, respectively. The
      mean IL-2 in serum samples of asthmatics and controls were 42.7 +/- 21.1 pg/ml
      and 30.3 +/- 2.4 pg/ml, respectively. Both levels did not result in any
      statistically significant difference between asthmatics and controls. There was
      no correlation between serum and sputum IL-2 levels, however sputum IL-2 levels
      correlated with percentage of sputum lymphocytes (p < 0.03, r = 0.51). The mean
      IL-10 levels in sputum samples of asthmatics and controls were 4.4 +/- 3.3 pg/ml
      and 3.9 +/- 5.9 pg/ml, respectively, the mean IL-10 level in serum of asthmatics
      and controls were 4.1 +/- 3.8 pg/ml and 2.3 +/- 2.5 pg/ml, respectively. We could
      not find statistically significant difference of serum or sputum IL-10 levels
      between asthmatics and controls. There was only correlation between serum and
      sputum IL-10 levels in asthmatics (p < 0.0008, r = 0.73). There was no difference
      between asthmatic subgroups regarding sputum and serum levels of IL-2 and IL-10.
      No correlation could be demonstrated between sputum or serum IL-2 and IL-10
      levels and clinical severity. CONCLUSIONS: We have demonstrated the presence of
      detectable concentrations of the IL-2 and IL-10 in serums and induced sputum
      samples of asthmatics, however, they have no predictive value for asthma since
      their levels are not increased in asthmatic patients over controls. Moreover, IL
      2 level positively correlated with lymphocyte percentage in induced sputum. The
      results suggest that measurement of IL-2 and IL-10 concentrations in serum and
      sputum will not be of diagnostic use in asthma and a reflection of the severity
      of asthmatic airway inflammation.

PMID- 15160445
TI  - Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and
      Russia.
AB  - AIM: The main aim of the study was to describe the differences between some
      Northern countries regarding what foods, according to the patients, elicit
      hypersensitivity symptoms. METHODS: At the participating clinics, patients with a
      history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire
      in which 86 different foodstuffs were listed. Skin-prick tests (SPT) were
      performed with common inhalant allergens. RESULTS: The foods that were reported
      as eliciting symptoms differed between countries. In Russia, Estonia, and
      Lithuania; citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish,
      tomato, egg, and milk were most often reported as causes of hypersensitivity. In
      Sweden and Denmark; birch pollen (BP) related foods, such as nuts, apple, pear,
      kiwi, stone fruits, and carrot were the most common causes. In all countries,
      children, more often than adults, had symptoms of allergic reaction to citrus
      fruits, tomato, strawberry, milk, egg, and fish. Most patients (95%) reported
      hypersensitivity to several foodstuffs (median: eight foods). The most common
      symptoms were oral allergy syndrome and urticaria. Severe symptoms were most
      common with fish, shellfish, nuts, and milk. Slight symptoms were most common
      with rice, coriander, poppy seed, lingonberry, corn, caraway red currant, and
      fig. Earlier well-known correlations, such as that between BP sensitization and
      some fruits and vegetables, as well as that between mugwort and some spices, were
      conoborated. Positive correlations were found between self-reported
      hypersensitivity to crustaceans and SPT with horse. A negative correlation was
      seen between hypersensitivity to crustaceans and SPT with BP. CONCLUSIONS: The
      foodstuffs that often are reported to cause food hypersensitivity, differ between
      Sweden/Denmark on one side and the Baltic States and Russia on the other. BP
      related foods dominate in Scandinavia, whereas some mugwort-related foods are of
      more importance in Russia and the Baltic States.

PMID- 15160448
TI  - Lessons in nursing.

PMID- 15160449
TI  - Fight your corner.

PMID- 15160447
TI  - Waiting on returns.

PMID- 15160450
TI  - On a mission.

PMID- 15160451
TI  - Too posh to push.

PMID- 15160452
TI  - The science bit.

PMID- 15160453
TI  - Mutual agreement.

PMID- 15160454
TI  - Supporting clinical skills developments.
AB  - The provision of clinical skills facilities in nursing and medical education
      centres has become more common (Bradley and Postlethwaite 2003, Ker et al 2003,
      Scott 2001), fuelled by calls to improve practitioners' fitness for practice
      (UKCC 1999), shared interprofessional learning (DoH 2001), and modernisation of
      the workforce (DoH 2000a). However, little attention appears to have been
      directed towards the pragmatic task of supporting these facilities. Support
      mechanisms were instituted in one school of nursing and midwifery to facilitate
      skills-based teaching and learning in a simulated clinical environment. The
      benefits of the new technical support worker role are discussed, including the
      more efficient use of learning resources and the positive learning experience of
      students.

PMID- 15160455
TI  - Skin problems in people with obesity.
AB  - AIM: To establish the level and type of skin problems in people with obesity and
      the extent to which they sought advice on their problem. METHOD: A self-report
      survey was carried out in a specialist nutrition clinic in Scotland during 2001.
      A convenience sample of 100 patients was selected. RESULTS: A majority (n = 75,
      75 per cent) of respondents had some type of skin problem. The main problems
      identified were itchiness and dry skin. The sites for skin problems varied
      although groin, limbs and beneath the breasts were the most prevalent areas. The
      two main causes of perceived skin problems were perspiration and friction. Forty
      four (59 per cent) had seen a doctor about their skin problem, but few (n = 12,
      16 per cent) had consulted other healthcare professionals and some (25 per cent)
      had not sought any advice. CONCLUSION: There is a considerable level of skin
      problems in this patient group, which has not previously been reported or
      identified as a significant potential co-morbidity. Therefore, nurses and other
      healthcare professionals should incorporate some form of skin assessment into any
      assessment of patients with obesity. Further research is needed to determine the
      specificity and degree of skin problems in those who are diagnosed as obese and
      the impact it has on their life and their weight management.

PMID- 15160458
TI  - [Evaluation of psychotherapies, a contested expertise].

PMID- 15160456
TI  - Promoting knowledge and awareness of skin cancer.
AB  - Skin cancer is the most common cancer in the UK and the incidence continues to
      increase. Jane Freak discusses the causes, treatment and prevention of skin
      cancer.

PMID- 15160459
TI  - [Medical information systems program, a medical information tool for nurses].

PMID- 15160460
TI  - [New regulatory incentives for home psychiatric services admission].

PMID- 15160463
TI  - [Towards health care management adapted for prisoners].

PMID- 15160464
TI  - [La Traviata, or office admission of prisoners].

PMID- 15160465
TI  - [Admission of prisoners into psychiatric services].

PMID- 15160466
TI  - [Psychiatric nurses in prison, a profession that questions].

PMID- 15160467
TI  - [Dimensions of nursing care in the prison milieu. Interview by Franck Fabien].

PMID- 15160469
TI  - [Closed spaces where words liberate].

PMID- 15160468
TI  - [Suicide prevention in prison].

PMID- 15160470
TI  - [From normal to "not too logical"].

PMID- 15160471
TI  - [The body in its lair].

PMID- 15160472
TI  - Key developments in gastroenterology.

PMID- 15160473
TI  - Casebook: anal pain.

PMID- 15160474
TI  - FAQs: gastrointestinal motility disorders.

PMID- 15160475
TI  - The management of oral conditions.

PMID- 15160476
TI  - Inflammatory bowel disease in general practice.

PMID- 15160477
TI  - Clinical approach to thyrotoxicosis.

PMID- 15160478
TI  - Current diagnosis and management of diabetes.

PMID- 15160479
TI  - A guide to the simulated surgery.

PMID- 15160481
TI  - Mechanisms of movement in cells and muscle. The Royal Society, London. 26th
      September 2003.

PMID- 15160482
TI  - The 32nd European Muscle Conference.

PMID- 15160483
TI  - Calponin (CaP) as a latch-bridge protein--a new concept in regulation of
      contractility in smooth muscles.

PMID- 15160484
TI  - Effects of ovariectomy and estrogen on skeletal muscle function in growing rats.
AB  - This study examined the effect of estrogen replacement on soleus muscle size and
      contractile function in ovariectomized rats during physiological growth. Seven
      week old female Sprague-Dawley rats were assigned to one of three treatment
      groups: (1) control animals (SHAM), (2) ovariectomized animals without estrogen
      replacement (OVX/CO), and (3) ovariectomized animals with 17 beta-estradiol
      replacement (OVX/E2). OVX/CO and OVX/E2 animals were pair-fed to SHAM animals to
      rule out the potentially confounding effect of differences in food intake. Rats
      were sacrificed 4 weeks after surgery and the soleus muscle was removed for
      analysis. Estrogen replacement reduced body weight, relative body weight gain,
      and soleus muscle fiber size despite all groups having a similar food intake.
      Ovariectomy alone had no effect on any of these parameters suggesting that
      estrogen may inhibit skeletal muscle growth when it is the only ovarian hormone
      present. Neither ovariectomy nor estrogen replacement affected maximal specific
      isometric force. Estrogen replacement increased half relaxation time. Ovariectomy
      resulted in a reduction in time to peak tension that was reversed with estrogen
      replacement. This reduction was not accompanied by a change in myosin heavy chain
      composition implying that calcium handling may have been altered. Results from
      this study suggest that estrogen affects skeletal muscle growth and twitch
      kinetics.

PMID- 15160485
TI  - Does the myosin V neck region act as a lever?
AB  - Recent research efforts from several groups have addressed the question of
      whether the amplitude of myosin's unitary step size is proportional to the length
      of the neck region. Unconventional myosin V, which has an extended neck region
      with 6IQ motifs, provides a natural template by which to test the lever arm model
      via mutational analysis. The most stringent test requires that a series of single
      headed molecules from the same myosin class be analyzed. Here we characterized
      the unitary mechanics of three single-headed fragments of myosin V expressed in
      the baculovirus/insect cell system. Each construct consisted of the motor domain
      (MD) and a variable number of IQ motifs (MD2IQ, MD4IQ and MD6IQ) that bind
      calmodulin, followed by an epitope tag so that the molecule can be attached to
      the nitrocellulose surface via an antibody. The results show a correlation
      between the unitary step size and the number of IQ motifs, confirming that the
      myosin neck region acts as a lever. The step size of MD2IQ is twice that observed
      from single-headed subfragments of class II myosins with the same neck length.
      Our results are discussed in relation to data obtained concurrently from other
      laboratories with similar constructs.

PMID- 15160486
TI  - Effect of sarcomere length on step size in relaxed rabbit psoas muscle.
AB  - Recent experiments have shown that shortening and stretching of sarcomeres in
      single activated and unactivated myofibrils occur in stepwise fashion (Yang et
      al. (1998) Biophys J 74: 1473-1483; Blyakhman et al. (2001) Biophys J 81: 1093
      1100; Yakovenko et al. (2002) Am J Physiol Cell Physiol 283: 735-742). Here, we
      carried out measurements on single myofibrils from rabbit psoas muscle to
      investigate steps in unactivated specimens in more detail. Activated and
      unactivated myofibrils were released and stretched in ramp-like fashion. The time
      course of length change in the single sarcomere was consistently stepwise. We
      found that in the unactivated myofibrils, step size depended on initial sarcomere
      length, diminishing progressively with increase of initial sarcomere length,
      whereas in the case of activated sarcomeres, step size was consistently 2.7 nm.

PMID- 15160487
TI  - Upregulation of HARP during in vitro myogenesis and rat soleus muscle
      regeneration.
AB  - Heparin affin regulatory peptide (HARP) is a heparin binding growth factor that
      belongs to a family of molecule whose biological function in myogenesis has been
      suspected without formal demonstration. In the present study, we investigated the
      expression and the distribution of HARP and its mRNA during soleus muscle
      regeneration using a crushed-induced regeneration model and also during
      differentiation of muscle satellite cells in primary cultures. We show that HARP
      mRNA and protein expression are increased during the regeneration process with a
      peak at day 5 after muscle crushing when new myotubes are formed. In situ
      hybridization and immunohistochemical studies showed that activated myoblasts
      expressed HARP at day two after crushing. Five days after muscle lesion, HARP is
      localised in newly formed myotubes as well as in prefused activated myoblasts. In
      regenerated myofibers, 15 days after crushing, expression of HARP was reduced. In
      vitro experiments using primary cultures of rat satellite cells indicated that
      HARP expression level increased during the differentiation process and peaked on
      fusion of myoblasts into myotubes. This is the first study demonstrating the
      presence of HARP in fusing myogenic cells suggests that this growth factor could
      play a function in myogenic differentiation.

PMID- 15160488
TI  - Contractile protein concentrations in human single muscle fibers.
AB  - The intent of this investigation was twofold: (1) to develop a convenient method
      for analyzing skeletal muscle protein concentrations in a large number of
      individual human single fibers and (2) to compare the myosin heavy chain (MHC)
      and actin concentrations in fibers expressing pure MHC I or MHC IIa. Individual
      vastus lateralis fibers were dissected from five individuals (3 M, 2 F; 24 +/- 1
      years) and used to determine single fiber total protein (TP) concentration and
      MHC distribution. Fibers expressing pure MHC I and MHC IIa were further analyzed
      for MHC (252 fibers; mean of 50/subject) and actin (160 fibers; mean of
      32/subject) concentration relative to TP. Single fiber MHC concentration was 26
      +/- 4% greater (P < 0.05) in MHC IIa (364 +/- 39 micrograms MHC/mg TP) vs. MHC I
      (266 +/- 29 micrograms MHC/mg TP) fibers. No differences (P > 0.05) were noted in
      single fiber actin concentration (MHC I: 171 +/- 17 micrograms actin/mg TP; MHC
      IIa: 165 +/- 17 micrograms actin/mg TP). These data indicate that within the TP
      fraction, skeletal muscle fibers contain differing amounts of MHC, and this
      appears to be fiber type specific. These data and methods have implications for
      the study of human muscle fiber type specific alterations in various protein
      concentrations in response to exercise, models of unloading, and aging.

PMID- 15160489
TI  - Molecular characterization of a PDZ-LIM protein in Atlantic salmon (Salmo salar):
      a fish ortholog of the alpha-actinin-associated LIM-protein (ALP).
AB  - A protein containing both PDZ and LIM protein-protein interaction motifs has for
      the first time been identified in a lower vertebrate species. A full-length cDNA
      encoding the ortholog of the alpha-actinin-associated LIM protein (ALP) was
      isolated from white skeletal muscle of Atlantic salmon (Salmo salar). Whereas ALP
      is expressed as two muscle specific isoforms in mammals and chicken as the result
      of alternative splicing, a single ALP transcript was found in both muscle and non
      muscular tissues of Atlantic salmon. On the other hand, Western blot analysis
      revealed several immunoreactive ALP variants in salmon muscle tissues, including
      a 45 kDa protein in white and red skeletal muscle and a 37-40 kDa protein in
      heart and smooth muscle. Salmon ALP and alpha-actinin showed similar striated
      patterns in serial longitudinal sections of white and red skeletal muscle and
      heart muscle. Expression of ALP was initiated at the 45-somite stage of the
      salmon embryogenesis contemporary with the first appearance of alpha-actinin
      transcripts. The similarities in both the spatial and temporal expression
      patterns of salmon ALP and alpha-actinin strongly indicate that the two proteins
      are associated as in higher vertebrates, and that the assumed involvement of ALP
      in the organization and/or maintenance of the Z-lines in striated muscle has been
      conserved during vertebrate evolution. However, in contrast to the restricted
      expression of ALP in higher vertebrates, the ubiquitous expression of salmon ALP
      suggest that this factor is involved in the assembly of additional multi-protein
      complexes in fish.

PMID- 15160490
TI  - Swimming exercise in infancy has beneficial effect on the hearts in
      cardiomyopathic Syrian hamsters.
AB  - The phenotypic expression of cardiomyopathy is greatly influenced by extrinsic
      factors other than intrinsic genetic defects, such as environmental stress.
      Exercise is assumed to be an important extrinsic factor, since sudden death is
      sometimes seen during exercise in young patients with hypertrophic cardiomyopathy
      (HCM). However, the long-term effects of mild exercise on phenotypic expression
      in cardiomyopathy remain unclear. To evaluate the effects of exercise performed
      during infancy or adolescence in cardiomyopathic patients, cardiomyopathic Syrian
      hamsters (BIO14.6) were subjected to swimming. BIO14.6 and age-matched congenic
      normal hamsters (CN) as controls were divided into three groups: sedentary (Sed),
      and trained during infancy (Inf) and during adolescence (Ado). Histological and
      biochemical analysis of 41-week-old hamsters revealed that (1) the relative level
      of beta-myosin heavy chain mRNA was significantly lower in the Inf group than in
      the Sed and Ado groups of BIO14.6. The level in the Inf group of BIO14.6 was
      compatible with that in the age-matched Sed group of the CN strain; (2) in
      BIO14.6, degenerative mitochondrial change in the cardiomyocytes was not seen in
      the Inf group while it was common in the Sed and Ado groups; (3) calcineurin
      phosphatase activity in the swimming group in 10-week-old CN was significantly
      higher than that of the age-matched sedentary group, and was as much as that of
      the swimming and sedentary groups in 10- and 41-week-old BIO14.6.

PMID- 15160491
TI  - Modulation of actomyosin motor function by 1-hexanol.
AB  - This study examines the effects of 1-hexanol as a perturbing agent on actomyosin
      ATPase and its related functions in the concentration range between 0 and 20 mM.
      In this range the denaturation of myosin subfragment 1 (S1), as measured by the
      inactivation rate of its K-EDTA-ATPase, and depolymerization of F-actin were
      insignificant. Major findings showed that hexanol had the following effects which
      were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10
      fold at 20 mM) without greatly affecting the enhancement of tryptophan
      fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release
      from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity;
      (c) an increase in the affinity of S1 for actin in the presence of ATP and a
      decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in
      the sliding velocity of actin filaments in in vitro motility assays with myosin,
      and (e) a decrease in isometric tension of single skinned muscle fibers. Thus,
      the effects of hexanol on actomyosin interaction are distinct for the weak and
      strong binding states, consistent with a change in the hydrophobic interaction in
      the interface between myosin and actin accompanying the transition from the weak
      to the strong binding state. Hexanol also accelerates the Pi release from
      S1.ADP.Pi, which is the transition step from the weak to the strong binding
      state. The fact that hexanol accelerates Pi release suggests that this alcohol
      perturbs the S1.ADP.Pi conformation. We speculate that this intermediate-specific
      structural perturbation is related to the inhibition of the maximum actin
      activated ATPase, in vitro motility, and isometric tension.

PMID- 15160492
TI  - Developmental induction of DHPR alpha 1s and RYR1 gene expression does not
      require neural or mechanical signals.
AB  - This study compares dihydropyridine receptor (DHPR) and ryanodine receptor (RyR1)
      gene expression in the diaphragm and hindlimb skeletal muscles of neonatal mice,
      and examines the contribution of neural and mechanical signals to their
      developmental induction in vivo. DHPR alpha 1s subunit and RyR1 protein are
      expressed concurrently, while their respective mRNAs are induced sequentially,
      with DHPR mRNA ahead of RyR1 mRNA. Both DHPR and RyR1 are more abundant in the
      diaphragm at birth, and become more abundant in the hindlimb at maturity. These
      patterns are consistent across different muscles and species. A critical period
      for DHPR alpha 1s and RyR1 gene expression in the hindlimb occurs between days 5
      and 19 postnatal. Their mRNA expression during this period is unchanged by
      denervation or tenotomy, but DHPR protein decreases after tenotomy. These results
      demonstrate that both transcriptional and post-transcriptional mechanisms
      contribute to the muscle-specific and coordinated assembly of the functional DHPR
      RyR1 complex, and that the developmental induction of DHPR and RyR1 gene
      transcription does not require neural or mechanical signals.

PMID- 15160494
TI  - On the mechanics of the actin filament: the linear relationship between stiffness
      and yield strength allows estimation of the yield strength of thin filament in
      vivo.
AB  - Comparison of the behaviour of actin filaments either modified with
      tetramethylrhodamine iodoacetamide or decorated with tetramethylrhodamine
      phalloidin or with tropomyosin or with myosin subfragment 1 shows that, in all
      the cases, yield strength is linearly related to stiffness.

PMID- 15160495
TI  - College prepares for close focus on its performance.

PMID- 15160496
TI  - The reality of a nursing vision.

PMID- 15160493
TI  - Engineering lysine reactivity as a conformational sensor in the Dictyostelium
      myosin II motor domain.
AB  - Lys84 of skeletal muscle myosin located at the interface between the motor and
      neck domains has long been utilized as a useful chemical probe sensing motor
      domain conformational changes and tilting of the lever arm. Here we report the
      first site-directed mutagenesis study on this side chain and its immediate
      chemical environment. We made Dictyostelium myosin II motor domain constructs in
      which Lys84 was replaced by either a methionine or a glutamic acid residue and
      another mutant containing an Arg704Glu substitution. By following
      trinitrophenylation of the mutant constructs, we first unambiguously identify
      Lys84 as the reactive lysine in Dictyostelium myosin. Analysis of the reaction
      profiles also reveals that the Lys84-Arg704 interaction at the interface of two
      subdomains of the myosin head has a significant effect on Lys84 reactivity, but
      it is not the only determinant of this property. Our findings imply that the
      nucleotide sensitivity of the trinitrophenylation reaction is a general feature
      of conventional myosins that reflects similar changes in the conformational
      dynamics of the different orthologs during the ATPase cycle.

PMID- 15160497
TI  - Leading a day-case medical unit. Interview by Rebecca Sandiford.

PMID- 15160498
TI  - Addressing barriers in headache care. Interview by Janis Smy.

PMID- 15160499
TI  - Guidelines for improving care in respiratory disease in the UK.
AB  - More than eight million people in the UK have respiratory conditions and one in
      four people die from them. We appear to be facing a major paradox with regard to
      the management of respiratory disease in the UK. Although we have a wide range of
      diagnostic tests and effective treatments at our disposal, we do not appear to be
      making any impact on the morbidity and mortality of respiratory disease.
      Respiratory disease needs to be moved onto the 'must do' agenda.

PMID- 15160500
TI  - What you need to know about ... antibiotics.

PMID- 15160501
TI  - Nurses can seize the opportunity to offer smoking interventions.

PMID- 15160502
TI  - Ensuring correct use of skincare products on peristomal skin.
AB  - Peristomal skin requires careful management to maintain its health and integrity.
      Although a wide range of skincare products is available, these should be used in
      response to clinical need, rather than routinely. This article discusses risks to
      peristomal skin, routine care, and use of products when the health of skin is
      compromised.

PMID- 15160503
TI  - Addressing the palliative care needs of people with dementia.
AB  - The palliative care needs of people with dementia have received little attention
      to date. In the early days of the disorder some drugs may assist with the
      cognitive and behavioural symptoms. However, as the disease progresses people
      with dementia become increasingly dependent on carers. Evidence suggests that a
      palliative care approach from diagnosis is beneficial because it addresses
      people's emotional needs as well as those of their families and carers.

PMID- 15160504
TI  - Staff perceptions of community learning disability nurses' role.
AB  - AIM: This study examines the views of health and social care staff in relation to
      their perception of the role of community learning disability nurses. METHOD: A
      total of 40 staff completed a questionnaire to identify the role and rate the
      effectiveness of community learning disability nurses. Inter-rater reliability
      was assessed and themes were identified. FINDINGS: Staff see community learning
      disability nurses as having service development, liaison and consultancy roles.
      However, respondents also continued to emphasise nurses' direct clinical role,
      with over 40 per cent identifying assessment and treatment. The perceived
      effectiveness of the community learning disability nurse was 4.09, SD = 0.71,
      indicating that staff generally perceived the service to be effective.
      CONCLUSION: Community learning disability nurses are viewed by their
      multidisciplinary colleagues as having a broad and varied role, which is
      consistent with the role, identified by nurses themselves. They may need to
      consider how to further develop their services in relation to clients' physical
      health. Overall, all participants rated the nursing service as effective.

PMID- 15160505
TI  - Securing your first job.

PMID- 15160506
TI  - A&E brings challenge and diversity.

PMID- 15160507
TI  - Coexistence of Hodgkin lymphoma and cyst hydatic disease of the liver.
AB  - Although both Hodgkin lymphoma and cyst hydatic disease in children have been
      seen with an increased frequency, there is no previously reported case of Hodgkin
      lymphoma associated with cyst hydatic disease from Turkey. The authors report
      such a case of Hodgkin lymphoma. Intrahepatic cystic masses were diagnosed during
      ultrasound examination for clinical staging on admission. The diagnosis of cyst
      hydatic of the liver was confirmed by surgery. Although there was no residual
      and/or new cyst formation on radiologic follow-up, elevated antibody titers
      (indirect hemagglutination test) persisted following surgical excision at least
      for 2 years of follow-up.

PMID- 15160508
TI  - Galactorrhea-associated granulosa cell tumor in a child.
AB  - Granulosa cell tumor of the ovary is a rare form of ovarian cancer in children.
      An 11-year-old girl was admitted with complaints of galactorrhea and abdominal
      mass. Abdomino-pelvic ultrasound and computed tomography revealed an ovarian
      tumor. Her prolactine and estradiol levels were increased but luteinizing hormone
      and follicle-stimulating hormone were decreased. An exploratory laparotomy
      revealed a giant solid mass, which was completely removed and determined as
      juvenile granulosa cell tumor. The clinical, hormonal, and radiological findings
      and the therapy of galactorrhea associated with granulosa cell tumor in a child
      are discussed. To our knowledge, this is first time it has been described in
      childhood.

PMID- 15160509
TI  - Gemcitabine and vinorelbine as a salvage regimen for relapse in Hodgkin lymphoma
      after autologous hematopoietic stem cell transplantation.
AB  - The authors describe two consecutive pediatric patients with relapsed Hodgkin
      lymphoma after autologous hematopoietic stem cell transplantation who had
      objective responses with a novel combination of gemcitabine and vinorelbine. This
      novel and promising combination needs to be studied in a larger number of
      relapsed Hodgkin disease patients.

PMID- 15160510
TI  - Meropenem plus amikacin versus piperacillin-tazobactam plus netilmicin as empiric
      therapy for high-risk febrile neutropenia in children.
AB  - The aim of this study was to evaluate the efficacy and safety of meropenem plus
      amikacin compared with piperacillin-tazobactam plus netilmicin for initial
      empirical antibiotic treatment of high-risk febrile neutropenia in children with
      cancer. Patients with hematologic malignancy (leukemia or stage III/IV non
      Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and
      patients with solid tumors who presented with fever and severe neutropenia (ANC <
      100/mm3) were considered to be at high risk and eligible for this study. In this
      prospective study, 33 patients with 50 febrile neutropenic episodes received i.v.
      neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in
      31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus
      netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was
      determined at 72 h and at completion of the therapy. The groups were comparable
      in terms of age, sex, initial ANC, use of growth factors, and classification of
      the infections. An infection was documented microbiologically in 12 episodes
      (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the
      piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological
      isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi.
      Most of the clinically documented infections were of lower respiratory tract,
      gastrointestinal mucosa, or urinary tract origin. The mean duration of
      neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs.
      5 days). The success rate with initial empiric therapy was 52% in the meropenem
      plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group,
      respectively (p = .5). Total success rate (with or without modification) was 97%
      vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients).
      No major adverse effects were observed in each group. Empirical therapy with
      meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk
      febrile neutropenia is equally effective and safe in pediatric cancer patients.

PMID- 15160511
TI  - Amifostine as differentiating agent in cord blood and bone marrow cultures from
      children with hematological disorders.
AB  - Amifostine protects normal tissues from the cytotoxicity of chemotherapy and
      radiotherapy and has an effect a growth factor both in vivo and in vitro. To
      evaluate its possible hemopoietic promoting activity, the authors studied the
      effect of WR-2721 on cord blood and bone marrow progenitors from children with
      hematological disorders and normal controls in semisolid cultures after
      preincubation with 0.1-1000 microM amifostine. Amifostine enhanced the growth of
      BFU-E in autoimmune neutropenia but inhibited CFU-GM development. It also exerted
      an inhibitory effect upon growth of committed progenitors in the groups studied
      (acute lymphoblastic leukemia, Langerhans cell histiocytosis), including cord
      blood and marrow of healthy controls.

PMID- 15160512
TI  - Spontaneous remission in congenital leukemia is not related to (mosaic) trisomy
      21: case presentation and literature review.
AB  - Congenital leukemia is seldomly diagnosed. Cases should be differentiated from
      transient leukemoid reaction, which is noted in Down syndrome. Outcome in
      congenital leukemia is poor, but spontaneous remissions have been described. The
      authors report on a female neonate with myeloid leukemia of the skin; no blood
      and bone marrow involvement was noted. Constitutional 47, XX, + 21 was excluded.
      In situ hybridization on a paraffin-embedded skin biopsy sample did not show
      trisomy 21 in the leukemia lesions. No antileukemia therapy was given. During
      follow-up, small nodules (diameter up to 3 mm) on the soles of both feet came and
      went over a 3-month period. The child is now 3.5 years old and well. To date, 18
      cases of congenital leukemia showing spontaneous remission have been described in
      the literature, almost exclusively myeloid leukemia (FAB M4 and M5). Congenital
      leukemia confined to the skin was described in only 4 cases. On follow-up, 6
      cases relapsed; only one of them initially had skin involvement only. The data
      from this patient and literature indicate that cytostatic treatment should start
      only if the malignancy interferes with vital parameters. In case of relapse or
      progression, initial postponement of chemotherapy in these frail neonates will
      result in less toxicity and probably a better survival.

PMID- 15160513
TI  - Lamivudine facilitates optimal chemotherapy in hepatitis B virus-infected
      children with hematological malignancies: a preliminary report.
AB  - Hepatitis B virus (HBV) reactivation is well documented in infected patients who
      have hematologic malignancies, precluding appropriate chemotherapy courses and,
      therefore, increasing the possibility of relapse of malignancies. The objective
      of this study was to evaluate lamivudine treatment to prevent hepatitis B
      reactivation in children with cancer who acquired infection with HBV and so allow
      completion of optimal chemotherapy. Ten children (7:3 M:F; median age: 9.8
      years), undergoing chemotherapy for hematological malignancies and suffering from
      immunosuppressive-induced hepatitis B virus reactivation, were treated
      concurrently with lamivudine (3 mg/kg bw, od) for up to 18 months. All were
      HBsAg+ve, HBsAb-ve, HBV-DNA+ve. Serology markers (HBsAg/Ab, HBeAg/Ab, HBV-DNA)
      and ALT were tested 3 monthly. Histological assessments were performed pre- and
      18 months post-lamivudine therapy. During lamivudine therapy chemotherapy courses
      were completed for all children, and none of the patients suffered reactivation
      of hepatitis. After a median follow-up of 10 months, remission of malignancy was
      maintained in 7/10 patients while 3 patients relapsed. HBeAg+ve seroconversion
      occurred in 4/9 HBeAg+ve children within 3 months. After 9 months of therapy,
      8/10 were HBV-DNA-ve. Six out of 7 children with histological evidence of chronic
      hepatitis showed marked improvement post-therapy. Lamivudine therapy for up to 18
      months in children receiving chemotherapy helped prevent recurrence of hepatitis
      B exacerbations and improved the underlying chronic hepatitis, while facilitating
      completion of appropriate chemotherapy regimens without compromise.

PMID- 15160514
TI  - Fetal ultrasonography to prevent irreversible neurological sequelae of neonatal
      neuroblastoma.
AB  - An intra-abdominal mass was observed by fetal ultrasonography at 32 weeks of
      gestation. The baby was diagnosed as having neuroblastoma at the time of delivery
      at 39 weeks and its lower extremities were completely paralyzed. The chemotherapy
      after birth was quite effective to reduce the mass volume but neurological
      sequelae failed to improve. By carefully monitoring the movement of extremities,
      it may have been possible to prevent irreversible by inducing delivery before
      that state was reached.

PMID- 15160516
TI  - Relapsed acute leukemia in children: Oman experience.
AB  - Acute leukemia (AL) is the most common malignancy in children in Oman. It
      accounts for over one-third of all childhood cancers, most of which
      (approximately 75%) are acute lymphoblastic leukemia (ALL). Over a decade, a
      total of 128 cases of childhood acute leukemia have been diagnosed and managed at
      Paediatric Haematology/Oncology Unit, Sultan Qaboos University Hospital, which is
      the national referral center of pediatric leukemia cases. A retrospective review
      of case notes was used to study all children with a diagnosis of acute leukemia
      from January 1993 to January 2003. All the cases were diagnosed using a bone
      marrow aspirate with morphological and immunophenotypic classification. Over this
      period, 24 cases relapsed. They were classified as per BFM group as "very early,"
      "early," and "late" according to the time from diagnosis to first relapse and
      were divided into isolated bone marrow (BM), extramedullary site, and combined
      relapse. Sixteen percent of ALL cases and 58.6% of acute myeloid leukemia (AML)
      cases so far relapsed. Most of the AML cases relapsed very early on in treatment.
      Eleven patients had combined relapse in BM and extramedullary site (9 in the
      central nervous system, 1 in the testicles, and 1 in the eye). The overall
      outcome of these patients is very poor, and only 6 patients out of 24 are still
      alive. In conclusion, the relapse rates of childhood AL are more or less similar
      to those of other reports but the overall outcome is very poor. A large majority
      of the patients in this study are either very early or early relapsers. Future
      studies including genetic and molecular analysis may be able to explain the
      difference in clinical outcome of these relapsed AL cases.

PMID- 15160515
TI  - Inter- and intraindividual variability in ketamine dosage in repetitive invasive
      procedures in children with malignancies.
AB  - Midazolam/ketamine sedation has been used successfully in children undergoing
      painful invasive procedures. The authors prospectively assessed inter- and intra
      individual variability in ketamine dosage for sedation in repetitive invasive
      procedures in children with malignancies. A total of 92 invasive procedures (58
      lumbar punctures, 34 bone marrow biopsies; range: 2-9 procedures/patient) were
      performed on 25 children (median age: 12 years). Intravenous sedation consisted
      of 0.1 mg midazolam/kg and 0.5-1.0 mg ketamine/kg. Incremental dosages of
      ketamine (0.33 mg/kg) were given if necessary to achieve or maintain deep
      sedation. Primary outcome measure was the inter- and intraindividual ketamine
      dosage required to achieve adequate sedation; secondary outcome measures were the
      number of procedures with adequate sedation (Ramsay score of > 4), the number of
      adverse side effects, and the need for therapeutic interventions. All 92 invasive
      procedures were completed with satisfactory sedation levels in 88 procedures
      (95.7%). There was a great inter- and intraindividual variability in ketamine
      dosage required to achieve or maintain adequate sedation. In 12% of procedures
      side effects were seen, which required no or only minor interventions. Due to
      great inter- and intraindividual differences, ketamine dosage should be titrated
      toward the desired level of sedation. Thus, ketamine can be adjusted to the
      individual's need while achieving adequate sedation.

PMID- 15160518
TI  - How to evaluate the acquisition of clinical skills at medical school: a tough
      question.

PMID- 15160517
TI  - Pulmonary dysfunction in pediatric oncology patients.
AB  - Children suffering from cancer may experience short episodes of respiratory
      distress and/or chronic impairment in pulmonary function. Pulmonary dysfunction
      may be primarily disease-related, but it may also result secondarily from
      treatment. Emergencies with critical respiratory dysfunction in childhood cancer
      include mechanical obstruction of vital anatomical structures and
      hyperleukocytosis syndrome. This paper focuses on the most relevant causes of
      respiratory distress and lung injury in pediatric oncology patients and bone
      marrow transplant patients. Infectious causes, lung disease resulting from anti
      neoplastic agents, and bone marrow transplant-related pulmonary dysfunction are
      emphasized. A review of the literature pertinent to this subject is given.

PMID- 15160519
TI  - A randomized and prospective study on the value of antibiotic prophylaxis
      administration in transurethral resection of the prostate.
AB  - CONTEXT: Antibiotic prophylaxis in transurethral resection of the prostate is a
      regular practice in urology. However, its prophylactic effect can be questioned
      when the antiseptic surgical technique is used. Nonetheless, urine culture
      oriented antibiotic therapy is the gold standard for avoiding improper medication
      usage and bacterial resistance. OBJECTIVE: To study the efficacy of antibiotic
      usage in patients with negative urine cultures, who were submitted to
      transurethral resection of the prostate. TYPE OF STUDY: Prospective open labeled
      study. SETTING: Tertiary care referral hospital. PARTICIPANTS: 124 consecutive
      patients, who were randomly divided into two groups to receive antibiotic
      prophylaxis or not. MAIN MEASUREMENTS: Cultures from meatus, urine, irrigation
      and antiseptic fluid, and prostate tissue chips, were compared and analyzed for
      bacterial sensitivity to the antibiotic used, according to the surgeon's personal
      criteria. McLennan's test was used for statistical analysis. RESULTS: No
      statistically significant difference regarding clinical evolution was found
      between the groups that received or antibiotics or not. Statistical significance
      was found regarding the occurrence of positive urine cultures during the
      postoperative period for those not receiving antibiotics, but not in relation to
      fever, prostate chip culture or bacteremic episodes. Sixty-eight subjects (57.1%)
      presented positive prostatic tissue culture. There was no specific correlation
      between the recovered bacteria from the meatus, prostatic tissue chip and urine
      and the spectrum of the administered antibiotic. Six cases showed the same
      bacteria in the urine and prostatic tissue chip. Only fifteen cases (25%) in the
      antibiotic group showed the desired sensitivity directed to the collected
      bacteria. CONCLUSIONS: Antibiotic prophylaxis for patients whose urine is sterile
      is debatable in patients who are candidates for transurethral resection of the
      prostate. Most of the time, the antibiotic agent used is not specific for any of
      the bacteria recovered from the various sources analyzed.

PMID- 15160520
TI  - Influence of sedation on morbidity and mortality in the intensive care unit.
AB  - CONTEXT: Although 30 to 50% of hospitalized patients in a critical care unit are
      under sedation, there is sparse data on the impact of sedation on morbidity and
      case-fatality rates in Brazil. Sedation is associated with higher risks of
      infection and death rate among patients. However, it is difficult to assess the
      clinical impact of sedation. OBJECTIVE: To evaluate the impact of sedation on the
      incidence of nosocomial infection and all-cause deaths at a critical care unit.
      TYPE OF STUDY: Prospective study. SETTING: Tertiary-care teaching hospital.
      PARTICIPANTS: After the exclusion of patients hospitalized for less than 24
      hours, 307 patients were assigned to two groups, considering their states of
      sedation. After confirmation of heterogeneity in relation to the Acute Physiology
      and Chronic Health Evaluation (APACHE II) prognostic system, 97 sedated and 97
      non-sedated patients were matched in relation to this severity index. MAIN
      MEASUREMENTS: Impact of sedation on deep venous thrombosis, incidence of
      decubital eschars, presence of infection, mortality and length of hospital stay.
      RESULTS: There was no difference in the incidence of deep venous thrombosis
      between the sedated and non-sedated groups, while the frequency of decubital
      eschars was significantly higher among sedated patients (p = 0.03). Infection was
      detected in 45.4% of patients under sedation and 21.6% of patients not under
      sedation (p = 0.006). Mortality for patients that did not receive any kind of
      sedative was 20.6% and, for those that were sedated during hospitalization, the
      role was 52.6% (p < 0.0001). The sedated patients had longer hospitalization (11
      vs. 4 days) (p < 0.0001). CONCLUSION: We concluded that sedation is associated
      with higher infection risk and case-fatality rate, and longer hospital stay.

PMID- 15160521
TI  - Clinical skills assessment: limitations to the introduction of an "OSCE"
      (Objective Structured Clinical Examination) in a traditional Brazilian medical
      school.
AB  - CONTEXT: Assessment of clinical skills has a central role in medical education
      and the selection of suitable methods is highly relevant. The OSCE (Objective
      Structured Clinical Examination) is now established as one of the most valid,
      reliable and effective tests for the assessment of clinical skills. OBJECTIVE: To
      describe student and faculty perceptions of an OSCE introduced in a traditional
      Brazilian medical school. TYPE OF STUDY: Descriptive, semi-quantitative study.
      SETTING: Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo.
      PARTICIPANTS: 258 junior medical students finishing an introductory course on
      basic clinical skills and six faculty members deeply involved with the OSCE
      administration. PROCEDURES: Over a period of three consecutive years, student
      perceptions on the examination were evaluated using a structured questionnaire
      containing several five-point scales; faculty members' opinions were collected
      using a structured questionnaire plus a personal interview. MAIN MEASUREMENTS:
      Student satisfaction or dissatisfaction with aspects of OSCE administration and
      positive or negative opinions from faculty members. RESULTS: Students were
      comfortable with cases and tasks, but nearly half (48%) of them criticized
      organizational aspects of the OSCE. Substantial proportions of students reported
      difficulties with both time management (70%) and stress control (70%).
      Improvement of several aspects of exams reduced criticism of organization to a
      minority (5%) of students, but the proportions of students reporting difficulties
      with time management (40%) and stress control (75%) during the exam remained
      virtually unchanged. Faculty members acknowledged the accuracy of the OSCE, but
      criticized its limitations for assessing the integrated approach to patients and
      complained that the examination was remarkably time and effort-consuming. The
      educational impact of the OSCE was felt to be limited, since other faculty
      members did not respond to the communication of exam results. CONCLUSIONS: In
      addition to shortage of resources and organizational difficulties, local cultural
      aspects and the absence of a more favorable educational climate may hinder
      lasting improvements in assessment methods in traditional medical schools.

PMID- 15160522
TI  - Allelic imbalance studies of chromosome 9 suggest major differences in
      chromosomal instability among nonmelanoma skin carcinomas.
AB  - CONTEXT: Loss of heterozygosity in the 9p21-p22 region, has been frequently
      described in a wide range of human malignancies, including familial melanomas.
      Also, losses and gains in other regions of chromosome 9 have frequently been
      observed and may indicate additional mechanisms for basal cell tumorigenesis.
      OBJECTIVE: To investigate allelic imbalance in the 9p21-p22 region, among basal
      cell carcinomas. TYPE OF STUDY: Microsatellite analysis. SETTING: Two dermatology
      services of public universities in Sao Paulo and the Laboratory of Cancer
      Molecular Genetics of Universidade Estadual de Campinas (Unicamp). PARTICIPANTS:
      13 patients with benign skin lesions consecutively referred to the outpatient
      dermatology clinics of Unicamp and Universidade Estadual de Sao Paulo (Unesp) and
      58 with malignant skin tumours. MEAN MEASUREMENTS: We examined 13 benign cases
      including four of solar keratosis, three keratoachanthomas, three melanocytic
      nevi, two of Bowen's disease and one of neurofibroma, and 58 malignant skin
      tumors: 14 of squamous cell, 40 basal cell carcinomas and four melanomas.
      Participating patients had the main tumor and a normal portion of non-adjacent
      skin surgically removed. DNA was extracted from the tumor and matching normal
      tissue. We used four sets of primers to amplify polymorphic microsatellite
      repeats on chromosome 9, two of them targeting the 9p21-p22 region. RESULTS: We
      identified eight cases (20%) of allelic imbalance among basal cell carcinomas,
      two cases of loss of heterozygosity and six cases of microsatellite instability
      in the 9p21-p22 region. Additional markers were also involved in three of these
      tumors. No events were detected among the benign or the other malignant cases.
      CONCLUSION: This phenotype dependency suggests that there is a major distinction
      between the two most important forms of nonmelanoma skin cancers in their
      tendency to present microsatellite instability in chromosome 9. Since the
      CDKN2a/p16INK4a, p19ARF and p15INK4b tumor suppressor genes do not appear to be
      responsible for the observed abnormalities, other genes at 9p21-p22 may be
      involved in the pathogenesis and progression pathway of basal cell carcinomas.

PMID- 15160523
TI  - Model of human epidermis reconstructed in vitro with keratinocytes and
      melanocytes on dead de-epidermized human dermis.
AB  - CONTEXT: Recent progress in the field of epithelial culture techniques has
      allowed the development of culture systems in which the reconstructed epidermis
      presents characteristics of morphological differentiation similar to those seen
      in vivo. Human epidermis reconstructed in vitro may be used as the best
      alternative for the in vitro testing of the toxicology and efficiency of products
      for topical use, as well as in the treatment of skin burns and chronic skin
      ulcers. OBJECTIVE: To demonstrate a method for obtaining human epidermis
      reconstructed in vitro, using keratinocytes and melanocytes cultivated on dead de
      epidermized human dermis. TYPE OF STUDY: Experimental/laboratory. SETTING: Skin
      Cell Culture Laboratory of the Faculdade de Ciencias Medicas, Universidade
      Estadual de Campinas, Campinas, Sao Paulo, Brazil. PROCEDURE: Human keratinocytes
      and melanocytes cultured in vitro were grown on a biological matrix (dead de
      epidermized human dermis) and the system was kept at an air-liquid interface, in
      a suitable culturing medium, until a stratified human epidermis was formed,
      maintaining the histological characteristics of the epidermis in vivo. RESULTS:
      It was histologically demonstrated that it is possible to reproduce a
      differentiated epidermis through keratinocytes and melanocytes cultured on dead
      de-epidermized human dermis, thus obtaining a correctly positioned human
      epidermis reconstructed in vitro with functional keratinocytes and melanocytes
      that is similar to in vivo epidermis. CONCLUSIONS: It is possible to obtain a
      completely differentiated human epidermis reconstructed in vitro from
      keratinocyte and melanocyte cultures on a dead de-epidermized human dermis.

PMID- 15160525
TI  - Multiple ectopic parathyroid adenomas.
AB  - CONTEXT: Primary hyperparathyroidism is the most common cause of hypercalcemia in
      unselected patients. The ectopic gland locations should be known for appropriate
      surgical exploration and for avoiding subsequent re-exploration that would
      represent higher morbidity. Multiple ectopic glands are rare and present a
      particular challenge in parathyroid surgery. CASE REPORT: A 65-year-old female
      presented with nephrolithiasis. Her serum total calcium was found to be elevated.
      The diagnosis of primary hyperparathyroidism was confirmed by the elevated serum
      intact parathyroid hormone levels. Ultrasound was only successful in localizing
      one adenoma in the lower right gland. Technetium sestamibi scanning correctly
      localized the same adenoma and showed another contralateral image, lateral to the
      thyroid cartilage. Fiber optic laryngoscopy showed an extrinsic mass pushing
      against the lateral and posterior walls of the left pyriform sinus. Resonance
      imaging revealed a soft tissue mass. RESULTS: The patient underwent bilateral
      neck exploration. Histopathological examination confirmed the diagnosis of
      parathyroid double adenomas. The late-stage postoperative checkups were normal.
      DISCUSSION: Routine bilateral neck surgery should be performed as a rule. We use
      ultrasound and technetium sestamibi scanning as a routine for preoperative
      localization studies. It is helpful to have an experienced surgeon for the
      localization.

PMID- 15160524
TI  - Pulmonary alterations in cocaine users.
AB  - CONTEXT: Brazilian researchers have recently recognized a marked increase in the
      number of people using abusable drugs and the consequences of this habit. It has
      become a major public health problem in a potentially productive segment of the
      general population. In the last few years, several medical articles have given
      special emphasis to pulmonary complications related to cocaine use. This review
      is based on this information and experience acquired with groups of cocaine
      users. OBJECTIVE: To present to physicians the pulmonary aspects of cocaine use
      and warn about the various effects this drug has on the respiratory system,
      stressing those related to long-term use. DESIGN: Narrative review. METHOD:
      Pulmonary complications are described. These may include infections
      (Staphylococcus aureus, pulmonary tuberculosis, acquired immunodeficiency
      syndrome/aids, etc.), aspiration pneumonia, lung abscess, empyema, septic
      embolism, non-cardiogenic pulmonary edema, barotrauma, pulmonary granulomotosis,
      branchiolitis obliterans and organizing pneumonia, pneumonitis and interstitial
      fibrosis, pneumonitis hypersensitivity, lung infiltrates and eosinophilia in
      individuals with branchial hyperreactivity, diffuse alveolar hemorrhage,
      vasculitis, pulmonary infarction, pulmonary hypertension and alterations in gas
      exchange. It is concluded that physicians should give special attention to the
      various pulmonary and clinical manifestations related to cocaine use,
      particularly in young patients.

PMID- 15160526
TI  - Bilateral adrenal metastases from a primary hepatocellular carcinoma.
AB  - Metastatic tumors to the adrenal gland are more common than primary adrenal
      carcinoma. However, bilateral adrenal metastases as the first manifestation of an
      occult or small hepatocellular carcinoma (HCC) are very rare. An elderly male
      presented with transient edema of lower limbs with findings of bilateral adrenal
      masses and a small liver lesion on CT scan. In spite of thorough biochemical and
      imaging investigative modalities the final diagnosis of metastatic carcinoma
      could be reached only after a needle core biopsy of the lesions.

PMID- 15160527
TI  - Laparoscopic ablation of peripelvic renal cysts.
AB  - Recently, laparoscopic surgery has been reported for symptomatic renal cysts. A
      60-year-old female was referred to Toyama Medical and Pharmaceutical University
      Hospital with a chief complaint of general fatigue and left back pain. CT
      demonstrated bilateral peripelvic renal cysts, and DIP demonstrated left
      hydronephrosis and a medical shift of the left renal pelvis. Laparoscopic
      ablation of bilateral peripelvic renal cysts was performed under general
      anesthesia and a round excision was made in the cyst wall via the peritoneum.
      After surgery, the left back pain disappeared and CT demonstrated resolution of
      peripelvic renal cysts. Laparoscopic ablation of peripelvic renal cyst is a
      highly effective and minimally morbid procedure.

PMID- 15160528
TI  - Primary primitive neuroectodermal tumor (PNET) of the kidney with venous
      thrombus.
AB  - Primitive neuroectodermal tumors of the kidney are rare, the diagnosis usually
      being made at histopathology. A young adult presented with a painful left renal
      mass. CT Scan of the abdomen revealed a large necrotic tumor of the left kidney.
      At surgery the patient was found to have a venous thrombus confined to the renal
      vein. Radical nephrectomy was done. Histopathology showed a round cell neoplasm
      with typical Homer Wright rosette formation and positive staining for neuron
      specific enolase (NSE) and MIC-2 on immunohistochemistry. The patient is
      undergoing multidrug chemotherapy and is alive and well at a follow up of nine
      months.

PMID- 15160529
TI  - Bilateral simultaneous tubeless percutaneous nephrolithotomy.
AB  - A case of bilateral inferior calyceal calculi treated with simultaneous bilateral
      tubeless percutaneous nephrolithotomy is presented. The patient had an uneventful
      recovery and was discharged in twenty-three hours.

PMID- 15160530
TI  - Massive intraabdominal extravasation of fluid: a life threatening complication
      following percutaneous nephrolithotomy.
AB  - Percutaneous nephrolithotomy provides an attractive alternative to the surgical
      removal of renal stones as it is associated with reduced patient morbidity and
      shortened hospital stay. The advantages of this procedure may, however, be
      overshadowed by complications like bleeding, extravasation of irrigant fluid and
      infection, which can be life threatening. We report a case of massive
      extravasation of irrigant fluid producing severe metabolic acidosis, persistent
      peritonism and ileus leading to a prolonged hospital stay. The patient also
      required a further surgery for the complete removal of the stones.

PMID- 15160531
TI  - Giant hydronephrotic kidney mimicking intestinal obstruction.
AB  - We describe a case of small bowel obstruction in a thirty-year-old adult male,
      which was discovered to be on account of a large hydronephrotic nonfunctioning
      kidney. An emergency percutaneous nephrostomy alleviated the massive abdominal
      distension and symptoms of small bowel obstruction. We have reviewed the causes,
      differential diagnosis and discussed the manner of such a unique and rare
      presentation.

PMID- 15160532
TI  - Dissolution of uric acid stones causing acute obstructing anuria in three
      consecutive infants.
AB  - We report on 3 infants with obstructive anuria due to bilateral uric acid stones.
      In all patients the precipitating cause of acute obstructive renal failure was
      choking of bilateral ureteropelvic junction with numerous small uric acid stones
      without cause pelvicaliceal dilatation. While the chemical dissolution therapy
      succeeded in dissolving the stones in 2 patients, unilateral percutaneous
      nephrostomy application associated with alkalization achieved dissolution of
      obstructing stones in the remaining 1 patient.

PMID- 15160533
TI  - Retrovesical migration of malpositioned double-j ureteral stent.
AB  - A case of extraperitoneal migration of a double-J ureteral stent in the
      retrovesical space as a result of malposition is being described. The management
      of this very rare complication of stent placement, which has never been reported
      in the international literature, is presented in detail.

PMID- 15160534
TI  - Ureteral metallic stents: application of virtual endoscopy for ureteral patency
      control.
AB  - OBJECTIVE: In the present study we have applied virtual endoscopy (VE) in
      patients with ureteral metallic stents as a follow-up tool study especially in
      the need to define ureteral patency. METHODS: We performed the suggested
      technique in 6 patients with malignant ureteral obstruction treated successfully
      by placement of Wallstent intraureteral metallic stents, and correlated the
      results with antegrade nephrostomography 48 hours after initial stent placement.
      RESULTS: In 2 patients restenosis was observed, and in the remaining 4 patients
      the stented ureters remained patent during the follow up evaluation. VE and
      antegrade nephrostomography, were concurrent as to their findings. Moreover, VE
      proceeds beyond the stenotic segment, allowing visualization of the ureteral
      lumen both cephalad and caudal to the point of obstruction. CONCLUSION: VE is
      providing indeed a more accurate, direct and dynamic approach in the evaluation
      of a strictured ureteral lumen within the metallic stent.

PMID- 15160535
TI  - Non-invasive methods of bladder cancer detection.
AB  - At present, the gold standard for the detection of bladder carcinoma is
      cystoscopy, often as part of the investigation of haematuria. There has been
      substantial research into the development of a non-invasive test for voided urine
      that would obviate the requirement for flexible cystoscopy. If such a test was
      100% sensitive and 100% specific, and was cost-effective, it could represent a
      way of separating patients who required tumour resection from those with no
      bladder carcinoma development. This article reviews the development of non
      invasive tests for the detection of bladder carcinoma, with emphasis on the most
      recent developments in fields such as microsatellite analysis, telomerase, and
      matrix metalloproteinase detection, in addition to the more widely researched
      tests such as NMP22 and BTA.

PMID- 15160537
TI  - Spontaneous resolution of bladder adenocarcinoma.
AB  - We report an unusual case of spontaneous resolution of bladder adenocarcinoma
      without any treatment. To our knowledge this is the first case of bladder
      adenocarcinoma that showed spontaneous regression, in English literature.

PMID- 15160536
TI  - Relation between bladder cancer and protein oxidation.
AB  - DNA, protein oxidation and lipid peroxidation possess a major impact in
      carcinogenesis. Also, inflammatory and oxidative events have remarkable
      importance in bladder cancer. Thus, in this study total protein, protein
      carbonyl, nitrotyrosine, thiol residues, non-protein thiols, lipid peroxidation,
      and also, because of their relations to the above parameters, iron and iron
      binding levels have been investigated in patients with bladder cancer and in
      control group. Statistical evaluation of the results demonstrated significantly
      lower plasma protein levels in the patients with bladder cancer, as compared to
      the healthy control group. Serum iron levels in patients with invasive bladder
      cancer were found to be significantly lower when compared with non-invasive
      group. Protein carbonyl groups were remarkably higher in bladder cancer patients
      than in healthy controls. Patients with bladder cancer were demonstrated to have
      significantly lower levels of total thiol groups and protein-bound thiol groups
      as compared to healthy controls. Protein-bound thiol groups in patients with
      invasive bladder cancer revealed a more significant decline, than in non-invasive
      group.

PMID- 15160538
TI  - Intraurethral prostatic cyst: a rare cause of infravesical obstruction.
AB  - A case is reported here of symptomatic intraurethral anterior midline prostatic
      cyst in a 52-year-old man whom transurethral resection of the cyst was performed
      successfully establishing the resolution of voiding symptoms.

PMID- 15160539
TI  - Serum concentrations of sex hormones in men with severe lower urinary tract
      symptoms and benign prostatic hyperplasia.
AB  - OBJECTIVE: To find out the impact of age-related changes in serum concentrations
      of sex hormones on the development of severe lower urinary tract symptoms and
      benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study group
      consisted of 61 consecutive patients subjected to prostatectomy for BPH between
      2000-2001 in our clinic. Forty-five randomly assigned, age and socioeconomically
      matched cases without any lower urinary tract symptoms were taken as the control
      group. Both clinical BPH and control groups were divided to 3 age groups (namely
      50-59, 60-69 and > or = 70 years) and age-related changes in serum concentrations
      of sex hormones were investigated. RESULTS: Prostate adenoma weight was found to
      be increased significantly (p = 0.02) with advancing age in clinical BPH group.
      There was no difference between serum concentrations of measured sex hormones
      between small and large prostates except for serum estradiol levels, which were
      found to be significantly higher in patients who had an adenoma weight of > 50 g
      (p = 0.047). Similar results were obtained in both clinical BPH and control
      groups with respect to age-related changes in serum concentrations of sex
      hormones. Briefly there was an age-related decrease in serum free testosterone
      levels and increase in serum estradiol, prolactin and gonadotropin levels. Serum
      free testosterone concentration was significantly higher in the control group for
      ages 60-69 (p = 0.015) while total testosterone was higher in BPH patients for
      patients older than 70 years of age (p = 0.027). No other significant change was
      documented between 2 groups. An age-dependent increase in serum E/freeT ratio was
      documented in both clinical BPH and control patients whereas serum freeT/T ratio
      was decreased in the BPH group with advancing age (p = 0.008). CONCLUSION: The
      decrease in serum free testosterone concentrations with a relative rise in serum
      estradiol levels with advancing age might be an important factor in the
      development of BPH. However it is likely that serum concentrations of sex
      hormones play little impact on the clinical severity of BPH.

PMID- 15160540
TI  - Sex cord tumour of the adult testis.
AB  - Sex cord stromal tumors are rare and account for approximately 6% of all
      testicular neoplasms. We report a case of sex cord tumor composed of granulosa
      cells and Sertoli cells in the adult testis.

PMID- 15160541
TI  - Myxoid liposarcoma of the spermatic cord: a case report and review of the
      literature.
AB  - Myxoid liposarcoma of the spermatic cord (MLSC) is a rare variance of spermatic
      sarcomas, with only 14 previous cases having been reported. Typically it presents
      during the seventh decade of life as a painless scrotal or inguinal mass.
      Although local recurrences are not uncommon, prognosis following complete tumour
      removal is good because metastases are rare. We describe one new case of a 24
      year-old male with incidental MLSC found during inguinal hernia repair, and also
      review the existing literature.

PMID- 15160542
TI  - Primary adenocarcinoma of the rete testis.
AB  - We report a case of adenocarcinoma of the rete testis in a 44-year-old man,
      presented intially with a hydrocele and later with signs of infection in the
      affected hemiscrotum. Multiple focal lesions within the testis appeared 6 months
      later in ultrasounds. After high inguinal orchiectomy, histology revealed a
      primary adenocarcinoma of the rete testis. Adenocarcinoma of the rete testis is a
      rare a highly malignant tumour originating in the mediastinum of the testis.
      Slightly over 40 cases have been reported in the literature. The treatment of
      choice is radical orchiectomy. Prognosis is poor; as mainly as 40% of patients
      die within the first year of diagnosis.

PMID- 15160543
TI  - Cooled lignocaine gel: does it reduce urethral discomfort during instillation?
AB  - INTRODUCTION: Topical urethral analgesia with 2% lignocaine gel for office
      procedures is an accepted practice in contemporary urology. However, instillation
      of 2% lignocaine gel into the urethra is associated with discomfort in some
      patients. MATERIAL AND METHODS: Forty consenting men reporting for cystoscopy
      under local anesthesia were randomized to receive 10 ml of 2% lignocaine
      hydrochloride gel at 4 degrees C and 22 degrees C. After instillation of the gel
      the patients were immediately asked to score the pain using a nongraphical visual
      analogue scale. RESULTS: The pain scores were analyzed using the paired Student's
      t-test. There was significant reduction in pain scores in the group receiving gel
      at 4 degrees C compared with the group at 22 degrees C (P < 0.05). CONCLUSION:
      Refrigerating the gel to 4 degrees C can significantly reduce the initial
      discomfort associated with instillation of 2% lignocaine hydrochloride into the
      male urethra.

PMID- 15160544
TI  - Pseudohypospadias with bilateral vesicoureteric reflux: consequences of
      inappropriate management of stricture urethra.
AB  - A 17-year-old male boy presented with clinical features of pseudohypospadias
      (small penile stump with absent distal penile urethra) associated with very small
      capacity bladder and bilateral grade IV vesicoureteric reflux following
      suprapubic urinary diversion for multiple urethro-cutaneous fistula and
      periurethral abscess which developed as a consequence of inappropriate initial
      management of urethral trauma. This case highlights the importance of the initial
      management of urethral trauma and the management of its rare complication.

PMID- 15160545
TI  - Bone mineral density in children with nocturnal enuresis.
AB  - In enuretic children there is a significantly higher incidence of fine and gross
      motor clumsiness, delayed developmental milestones, slower and poor linear
      growth, and these patients are shorter than normal children. Skeletal maturation
      of enuretic children has been determined with bone age in only two studies
      before, but to our knowledge bone mineral content of enuretic children has not
      previously been determined by bone mineral density measurement. Bone mineral
      density was measured by the dual-energy x-ray absorptiometry method in children
      with nocturnal enuresis and compared with that of a control group to detect
      whether there were any delay in bone development and any decrease in bone mass.
      Thirty enuretic children were compared with a control group of 40 healthy
      children with respect to body height and weight measurements, daily calcium
      intake, serum calcium, phosphorus and ALP levels, chronological and bone ages,
      and bone mineral density measurements. Of the parameters compared, bone age was
      significantly retarded, and bone mineral density was significantly reduced in
      children with enuresis (8.3 +/- 1.9 vs 9.7 +/- 2.3 years; p = 0.01, and 0.5476 +/
      0.07 vs 0.6077 +/- 0.05 g/cm2; p = 0.001, respectively). Chronological ages
      demonstrated a significant correlation with the bone ages in both the study and
      control groups (r = 0.852, p < 0.001, and r = 0.844, p < 0.001, respectively).
      However, the mean chronological age was significantly greater than the mean bone
      age in the study group (p < 0.001), whereas the mean chronological age was not
      significantly different from the mean bone age in the control group (p = 0.514).
      To clarify the exact mechanism responsible for these manifestations of skeletal
      maturation retardation, the relationship between the maturational delay of the
      central nervous system connections or the effect of any perinatal insult and the
      retardation in skeletal maturation remains to be determined.

PMID- 15160546
TI  - Stone fragility: its therapeutic implications in shock wave lithotripsy of upper
      urinary tract stones.
AB  - OBJECTIVE: To analyse the impact of stone composition on stone fragility
      (fragmentation) and clearance of upper urinary tract stones after shock wave
      lithotripsy (SWL). MATERIAL AND METHODS: Between 1st July 1998 and 31st July
      2001, 300 renal and ureteric units of 290 patients (10 being bilateral) underwent
      SWL for upper urinary tract calculi. The degree of fragmentation was divided into
      four types: (I) Excellent, (II) Good, (III) Fair and (IV) No fragmentation. Stone
      composition was done by X-ray diffraction crystallography. A statistical
      comparison was made between degree of fragmentation, number of shock waves
      delivered, voltage setting, number of sessions required and requirements of
      adjuvant procedures according to the stone composition. RESULTS: Stone analysis
      revealed that 90% of the patients had calcium oxalate stones. Of these 80% were
      calcium oxalate monohydrate (COM) and 20% calcium oxalate dehydrate (COD).
      Struvite, apatite and uric acid stones comprised of 6%, 3% and 1% respectively.
      Type-I fragmentation was achieved up to 63.96%, 50% and 100% in COD, struvite and
      uric stones respectively as compared to 44.9% and 44.44% for COM and apatite
      stones. Type-III fragmentation was seen up to 8.79% and 33.3% respectively in COM
      and apatite as compared to 5.55% or less in other types of the stones suggesting
      that COM and apatite stones produce larger fragments. The mean number of shock
      waves, voltage and number of treatments was significantly higher for COM and
      apatite stones (p value < 0.005) with a stone free rate of only 65-66% and 65-68%
      respectively at three months (p value < 0.001). Similarly the number of adjuvant
      procedures required in COM alone was more, i.e. 31 as compared to 17 procedures
      in rest of the other kinds of stones (p value < 0.05). CONCLUSION: Stone
      composition in Indian subcontinent is different from the western world. Fragility
      of a stone varies with the composition of the stone and affects the therapeutic
      results.

PMID- 15160548
TI  - Clinical factors associated with achieving K/DOQI hemoglobin targets in
      hemodialysis patients.
AB  - BACKGROUND: Few studies have assessed treatable factors associated with achieving
      the Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline of hemoglobin
      values of 11 to 12 g/dL in anemic hemodialysis patients. METHODS: This was a
      retrospective study of 30,029 prevalent hemodialysis patients with mean
      hemoglobin values less than 11 g/dL between January 1 and March 31, 1999. We
      studied the associations between demographic characteristics, comorbid
      conditions, disease severity, urea reduction ratio, epoetin doses, intravenous
      iron doses, and mean hemoglobin values in the ensuing 3 months. RESULTS:
      Approximately half (51.3%) of patients reached a mean hemoglobin value of at
      least 11 g/dL. By multiple logistic regression, the major factors showing a
      positive association with this outcome included a urea reduction ratio greater
      than 75% (odds ratio [OR], 1.23; P < 0.0001) and intravenous iron (OR: for 0
      vials/month, 1; for < 1, 1.22; for 1 to 1.9, 1.36; 2 to 2.9, 1.48; for 3 to 3.9,
      1.61; for > or = 4, 1.79; P < 0.0001), while a negative association with
      hemoglobin response, possibly representing epoetin resistance, was shown for
      initial severity of anemia (OR: for initial hemoglobin value < 7 g/dL, 0.06; for
      7 to 7.9 g/dL, 0.12; for 8 to 8.9 g/dL, 0.23; for 9 to 9.9 g/dL, 0.45; for 10 to
      10.9 g/dL, 1; P < 0.0001) and epoetin doses in the highest quintile (OR for >
      38,000 units/wk, 0.76; P < 0.0001). CONCLUSION: In patients with persistently low
      hemoglobin values, optimizing urea clearance and a proactive approach to
      intravenous iron therapy may enhance epoetin responsiveness.

PMID- 15160547
TI  - Oxidative stress markers and C-reactive protein in end-stage renal failure
      patients on dialysis.
AB  - OBJECTIVE: The inflammatory status is a well-documented factor influencing the
      development of oxidative stress in dialysis patients. This study intends to
      evaluate the inflammatory activity and the plasma levels of total antioxidant
      capacity (TAC) and lipid peroxidation products in patients on peritoneal dialysis
      (PD), by comparison with hemodialysis (HD) patients. PATIENTS AND METHODS: Plasma
      concentration of TAC, lipid peroxidation products and C-reactive protein (CRP)
      were measured in 24 patients on PD, 32 HD patients (pre and post treatment) and
      16 normal controls (NC). RESULTS: All patients had higher levels of TAC and lipid
      peroxidation products than NC (p < 0.001). Patients on PD, had similar levels to
      patients before HD but significantly higher (p < 0.001) than those post HD. The
      CRP concentration was higher in HD than in PD patients (p < 0.05). The percentage
      of patients with CRP > 10 mg/l was 48% in HD patients and 21% in PD patients. No
      correlation was observed between CRP and TAC nor CRP and MDA levels. CONCLUSIONS:
      We conclude that although PD and HD patients show an equal susceptibility in
      oxidative stress, CRP levels are higher in HD patients and this is indicative of
      a higher degree of inflammatory activity in these patients.

PMID- 15160549
TI  - Skeletal effects of erythropoietin in hemodialysis patients.
AB  - AIMS: To assess the effects of erythropoietin (EPO) on bone metabolism in
      patients receiving chronic hemodialysis (HD). METHODS: Forty one patients were
      divided into two groups whether they required the administration of EPO to treat
      renal anemia or not. Serial measurements of predialysis blood samples and bone
      mineral density were performed prospectively over a year. RESULTS: The
      administration of EPO was associated with an increased serum creatinine (11.9 +/-
      0.4 to 12.5 +/- 0.4 mg/dl, p < 0.05), insulin-like growth factor binding protein
      (3.0 +/- 0.2 to 3.4 +/- 0.2 micrograms/ml, p < 0.05) as well as decreased iron
      level (112 +/- 7 to 88 +/- 7 micrograms/dl, p < 0.005). Furthermore, in EPO
      treated group, exogenous EPO doses correlated with the increments in 1,25
      dihydroxy-vitamin D (r = 0.38, p < 0.05), intact osteocalcin (r = 0.42, p < 0.05)
      and bone alkali-phosphatase (r = 0.53, p < 0.005), but not intact parathyroid
      hormone (r = 0.09). Both metacarpal index (0.47 +/- 0.02 to 0.47 +/- 0.02) and
      the summation of gray scale/diameter (2.68 +/- 0.06 to 2.61 +/- 0.07 mmAl), bone
      mineral density parameters, remained unchanged. CONCLUSION: The present data
      provide evidence that EPO may modulate the production of 1,25-dihydroxy-vitamin D
      in HD patients. Furthermore, our findings suggest that EPO therapy activates
      insulin-like growth factor system in HD patients, possibly through its actions on
      metabolism.

PMID- 15160550
TI  - Are elderly haemodialysis patients at risk of falls and postural hypotension?
AB  - BACKGROUND: The numbers of older people on haemodialysis is rising. As aging and
      renal failure are risk factors for autonomic failure and haemodialysis involves
      significant fluid shifts we hypothesized that older patients would be susceptible
      to hypotensive events between dialysis sessions. Postural hypotension is a risk
      factor for falls. Falls are debilitating and a leading cause of morbidity and
      mortality in the elderly. AIM: To investigate whether postural hypotension and
      symptoms of hypotension and falls are common in older haemodialysis patients.
      METHODS: All 47 patients from a single unit aged 70 or over were asked about
      falls in the previous year and about symptoms that could be due to hypotension
      (syncope, presyncope, dizziness) between dialysis sessions. Twenty-three patients
      underwent pre- and post-dialysis orthostatic blood pressure measurement, 18 had
      44 hour ambulatory blood pressure recording and 10 subjects had full autonomic
      function testing. RESULTS: Of 47 patients interviewed, 20 reported syncope/pre
      syncope, 34 reported dizziness and 14 recalled at least one fall in the previous
      year. 8/23 had orthostatic hypotension pre-dialysis and 16/23 post-dialysis. Mean
      44-hour blood pressure was 134/68 (+/- 21/9) with no nocturnal dip. Autonomic
      function was abnormal in all 10 subjects tested. CONCLUSIONS: Elderly
      haemodialysis patients have a high incidence of hypotensive symptoms between
      dialysis sessions, recalled falls in the previous year and significant postural
      hypotension post-dialysis. Physicians supervising elderly haemodialysis patients
      should ask about symptoms between dialysis sessions and explore the possibility
      of hypotensive events in symptomatic patients.

PMID- 15160551
TI  - Urinary incontinence in primary care: a comparison of older African-American and
      Caucasian women.
AB  - Urinary incontinence is a common problem for aging women. Little is known about
      urinary incontinence in nonwhite populations. A telephone survey was used to
      compare the prevalence and severity of urinary incontinence as well as common
      risk factors for urinary incontinence in 194 African-American (AA) and Caucasian
      (C) women over the age of 50 who made a visit to a primary care practice within
      the prior 2 years. A high prevalence of UI was found among these women (62%AA,
      67%C), though no significant difference was noted among the two groups. More
      Caucasian women than African-American women reported symptoms of stress
      incontinence. For both groups, the use of HRT was associated with reporting
      urinary incontinence. Higher body mass index and prior hysterectomy was
      associated with urinary incontinence for African-American women only. For both
      groups, low rates of 'botheredness' (28%AA, 32%C) and treatment seeking (39%AA,
      52%C) were found.

PMID- 15160553
TI  - Nephropathology quiz page. Atheroembolic emboli.

PMID- 15160552
TI  - Prevalence and pathogenesis of hypokalemia in patients on chronic peritoneal
      dialysis: one center's experience and review of the literature.

PMID- 15160554
TI  - [Non-respiratory cyanosis in the newborn].
AB  - Four term babies, three boys and one girl, became cyanotic shortly after birth.
      In two cases the cause was maternal use of drugs: methemoglobinaemia due to use
      of a chromate and depression of the nervous system due to clomipramine. They
      recovered. A third child suffered cerebral infarction and was left with decreased
      left-arm function. The fourth child had a hypoplastic left heart and died.
      Central cyanosis in a newborn should be cause for concern. A thorough case
      history should be taken and extensive physical examination carried out. In case
      of doubt additional diagnostic tests should be performed.

PMID- 15160555
TI  - [Health Council of the Netherlands advisory report 'Vaccination against
      pertussis'--time for a new vaccine].
AB  - An advisory report on vaccination against pertussis by the National Vaccination
      Programme Review Committee of the Health Council of the Netherlands makes
      recommendations on improving pertussis vaccination in the Netherlands. Since
      1996, between 4000 and 8000 cases of pertussis have been reported each year,
      mainly in young children who have already been vaccinated. The main cause of this
      increase, apart from decreasing immunity in older children and adults, seems to
      be diminished vaccine effectiveness due to the occurrence of non-vaccine related
      strains of the pertussis bacterium in the Netherlands. The cellular vaccine used
      in the Netherlands contains low levels of the major antigens pertussis toxin and
      pertactin. The Health Council recommends the fastest possible transition to the
      use of an acellular combination vaccine. Such a vaccine will be effective and
      will have considerably fewer side effects than the one currently in use. The
      Committee recommends that research is done into the sources of pertussis
      infections in young infants.

PMID- 15160556
TI  - [The practice guideline 'Hypertension' (third revision) from the Dutch College of
      General Practitioners; a response from the perspective of general practice].
AB  - In the revised practice guideline on hypertension from the Dutch College of
      General Practitioners, some changes have been made in the areas of diagnosis and
      therapy in comparison to the previous edition. Finding people with hypertension
      is a major goal for the prevention of cardiovascular disease. A systolic blood
      pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non
      pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers,
      angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as
      monotherapy or in combination. In view of the ever-increasing importance of ACE
      inhibitors in antihypertensive therapy, we expect that the next revision of the
      practice guideline will soon be necessary.

PMID- 15160557
TI  - [The practice guideline 'Hypertension' (third revision) from the Dutch College of
      General Practitioners; a response from the perspective of internal medicine].
AB  - The revised practice guideline on hypertension from the Dutch College of General
      Practitioners is a useful document for the management of hypertension. The
      decision to limit antihypertensive treatment to patients with at least a 20% risk
      of developing cardiovascular disease within 10 years may, however, be criticised.
      Prolonged untreated mild hypertension may lead to macro- and microvascular
      myocardial sclerosis and disturbed systolic and diastolic function of the left
      ventricle. A 10% risk is preferred. On the other hand, case-finding and treatment
      of patients with hypertension will increasingly be a major time-consuming
      activity in general practice. This calls for a change in organisation: well
      trained vascular assistants should be employed to fulfill most of this task.

PMID- 15160558
TI  - [Summary of the practice guideline 'Hypertension' (third division) from the Dutch
      College of General Practitioners].
AB  - The revised practice guideline on hypertension from the Dutch College of General
      Practitioners has been brought in agreement with the guideline on hypertension
      from the Dutch Institute for Health Care Improvement. The main changes with
      regard to the former edition are: The threshold values for the diagnosis
      'hypertension' have been lowered to 140 mmHg and 90 mmHg for the systolic and
      diastolic blood pressures, respectively. Annual screening for hypertension in the
      elderly is no longer recommended. Henceforth, blood pressure measurement once
      every five years is considered sufficient, unless the blood pressure is known to
      be in a borderline area in which treatment is being considered. Often, the
      decision as to whether a patient should take antihypertensive drugs no longer
      depends on the presence of hypertension as such: to receive drug treatment, the
      patient should have at least a 20% risk of developing a cardiovascular disease in
      the next 10 years. To aid in estimating this risk for individual patients a risk
      table has been devised. Diuretics and beta-blockers are the drugs of first
      choice. If the blood pressure remains too high, angiotensin-converting-enzyme
      (ACE) inhibitors and calcium-channel blockers may be added.

PMID- 15160559
TI  - [Clinical reasoning and decision-making in practice. A 76 year old woman with
      gastric carcinoma and cardiac valve disease].
AB  - A 76-year-old woman with combined aortic and mitral valve disease presented with
      anaemia due to a gastric carcinoma. Further staging revealed no evidence for
      metastatic disease. Approval for surgery for the carcinoma was obtained after a
      cardiologist and anaesthesiologist were consulted. On the day of surgery,
      however, the attending anaesthesiologist estimated the operative risk to be
      unacceptable. The patient reversed her decision and decided not to have the
      oncological operation, as she felt well at the moment and considered the limited
      additional survival time not worth the anxiety. The expert opinion of an
      anaesthesiologist, a cardiologist and an oncologist not primarily involved in
      this case show that they differ as to the question who is responsible for the
      decision-making process in patients such as this one. The evidence on estimating
      operative risk in patients with cardiac valve disease undergoing noncardiac
      surgery is not unequivocal. Furthermore, there is a shared responsibility when
      more physicians are involved in the process of decision-making. Agreement on
      operative risk between physicians is necessary in order to prevent transfer of
      conflicting information to the patient.

PMID- 15160560
TI  - [Diagnostic image (188). A man suffering from a swollen and red arm. Deep venous
      thrombosis of the arm].
AB  - A 25-year-old man presented with a deep venous thrombosis of the left arm due to
      excessive lifting of household materials (Paget-Schroetter syndrome).

PMID- 15160561
TI  - [Very slight chance of other metastases in axillary nodes of breast cancer
      patients with a small sentinel node metastasis without extranodal tumor growth].
AB  - OBJECTIVE: To determine in patients with mammary carcinoma and a sentinel node
      metastasis whether pathological parameters of the sentinel node metastasis and
      the primary tumour might have predictive value with respect to the presence of
      metastases in other axillary nodes. DESIGN: Prospective. METHOD: The study group
      consisted of the first 100 consecutive patients with a sentinel node metastasis,
      who subsequently underwent a complete axillary dissection. The patients with
      metastases in the non-sentinel nodes were compared to those without such
      metastases regarding the size of the largest sentinel node metastasis and the
      presence of extranodal tissue invasion near any such node, and size, and type of
      the primary tumour. RESULTS: The median size of the metastases in the sentinel
      lymph node in the two groups was 3 mm versus 13 mm respectively (p < 0.001) and
      the frequency of extranodal tissue invasion 3% versus 74% respectively (p <
      0.001); the combination of these factors strongly predicted the presence of non
      sentinel lymph node metastases in the axilla (94% area under the receiver
      operating characteristics curve). None of the 30 patients with a micrometastasis
      < or = 2.0 mm in the sentinel lymph node had metastases in the non-sentinel
      axillary lymph nodes. Metastases were present in the non-sentinel axillary lymph
      nodes in 29 of the 31 patients with extranodal tissue invasion near the sentinel
      node. CONCLUSION: In breast cancer patients with a sentinel lymph node metastasis
      < or = 2.0 mm and without extranodal tumour growth a complete axillary lymph node
      dissection might be unnecessary as the risk of additional metastases was very
      small.

PMID- 15160562
TI  - [Four family members with proximal myotonic myopathy].
AB  - A 41-year-old woman had a 15-year history of pain in her thighs and arms, which
      also became weaker, and a decrease in visual acuity. Her 35-year-old brother,
      their 38-year-old sister and their 64-year-old mother also had myalgia, myotonia
      and proximal muscle weakness, and the women also had cataracts. Additional
      examinations and tests led to a diagnosis of proximal myotonic myopathy (PROMM)
      in all four cases. Neurological and ophthalmological follow-up was provided on a
      yearly basis, including ECG. The clinical features of PROMM display similarities
      to the adult form of myotonic dystrophy (MD) but differ in the proximal
      localisation of the muscle weakness and the frequent occurrence of pain in the
      affected muscles. PROMM is an autosomal dominant hereditary multisystemic
      disorder with a less serious course than MD and is rarely accompanied by
      cognitive disorders. In most cases, a genetic defect on chromosome 3q21 is the
      cause of the disease. A probable diagnosis can be made on the basis of the
      clinical symptoms and the results of simple laboratory tests, and can be
      confirmed via DNA analysis. As yet, the disorder can only be treated
      symptomatically, preferably via a multidisciplinary approach by a neurologist, an
      ophthalmologist, a cardiologist and a rehabilitation specialist.

PMID- 15160563
TI  - [Subclinical hypothyroidism; the start of a clinical trial into the usefulness of
      treatment with radioactive iodine].
AB  - Subclinical hyperthyroidism is defined as the presence of serum free thyroxine
      (T4) and triiodothyronine (T3) levels within the reference range and a reduced
      serum thyrotrophin (TSH) level. Evidence is accumulating that it has important
      clinical effects. Randomised clinical trials are needed to answer the question
      whether or not treatment of subclinical hyperthyroidism prevents cardiac
      problems, especially atrial fibrillation, and preserves bone mineral density. A
      randomised, Dutch multicentre trial has recently been started. Its goal is to
      study whether radioiodine treatment prevents the development of atrial
      fibrillation and prevents decreases in bone mineral density.

PMID- 15160564
TI  - [Better prognosis and favorable tumor stages in patients with invasive breast
      mammary carcinoma after introduction of the mass screening of breast cancer in
      Tilburg, the Netherlands].

PMID- 15160565
TI  - [Conscious refusal of food and fluids by Dutch nursing home patients in order to
      hasten death: a matter for patient and physician?].

PMID- 15160567
TI  - [Gallstones following considerable weight loss and recommendations for their
      prevention].

PMID- 15160568
TI  - Introducing a nurse-led clinic for patients who self-harm.
AB  - A fortnightly self-harm clinic was set up for patients from a secure psychiatric
      unit. This prize-winning paper describes how it both reduced admissions to A&E
      and won the support of patients, who became involved in their wound care.

PMID- 15160566
TI  - [Treatment of optic neuritis].

PMID- 15160569
TI  - Effects of ultrasound delivered through a mist of saline to wounds in mice with
      diabetes mellitus.
AB  - OBJECTIVE: To examine the effects of ultrasound administered through a fine mist
      of saline on surgically placed full-thickness excisional wounds in mice with
      experimental diabetes mellitus. METHOD: Fifty male CD-I mice received alloxan
      monohydrate (100 mg/kg), a drug known to induce diabetes mellitus. The animals
      received five ultrasound (n = 27) or sham (n = 23) treatments for 1.5 minutes, on
      alternate days, for 10 days, and were then sacrificed. Following sacrifice, each
      animal's wound was excised and the tissues prepared for qualitative and
      quantitative histological analysis. RESULTS: No difference in wound-surface area
      was found between the groups after the treatment period. However, blinded
      assessment of tissue sections revealed significantly increased deposition of
      collagen and blood vessels in the granulation tissue of animals treated with
      ultrasound compared with those that received sham therapy. CONCLUSION: Ultrasound
      delivered through a fine mist of saline significantly altered the composition of
      newly formed granulation tissue in animals with experimental diabetes mellitus.
      Further research needs to be completed to determine other effects of this novel
      ultrasound therapy and to examine its clinical effectiveness.

PMID- 15160570
TI  - A trial to determine the role of placental extract in the treatment of chronic
      non-healing wounds.
AB  - OBJECTIVE: To investigate the effect of topical placental extract in the
      treatment of non-healing wounds. METHOD: One hundred patients attending the wound
      clinic at University Hospital, Varanasi, India, with wounds of more than six
      weeks' duration were recruited. Fifty patients were treated with placental
      extract, and 50 were controls. Wound biopsy and swab culture and sensitivity were
      performed and the area surrounding the wound was X-rayed. Wound size was measured
      and the rate of epithelialisation assessed at weekly follow-ups. In nine cases
      biopsies were repeated after two weeks of treatment and sent for
      histopathological examination, including angiogenesis. RESULTS: Thirty patients
      dropped out, leaving 40 cases in the treatment group and 30 in the control group.
      Over an eight-week period, 27 patients (67.5%) in the treatment group showed more
      than 50% epithelialisation, compared with only seven patients (23.3%) in the
      control group. CONCLUSION: Placental extract has a beneficial role to play as a
      topical agent in the management of chronic non-healing wounds.

PMID- 15160571
TI  - Our agenda is to raise the standard of venous leg ulcer care.
AB  - This is the first of six articles on how to tackle the challenges faced when
      caring for patients with leg ulcers, with the aim of improving services and
      patient outcomes. This paper overviews diagnosis, treatment options and delivery
      of care.

PMID- 15160572
TI  - Educational intervention in the management of acute procedure-related wound pain:
      a pilot study.
AB  - OBJECTIVE: This report describes the pilot testing of an educational intervention
      to manage acute pain associated with wound care in an outpatient clinic. The
      intervention included essential elements of pain education identified in the
      acute pain literature: provision of information; pain measurement; establishing
      expectations; treatment planning; teaching environment. METHOD: The intervention
      was tested on five patients attending a wound clinic for scheduled treatment.
      Patients were aged 65 years or older and had a history of experiencing pain
      during treatment procedures such as dressing changes and debridement. Before the
      intervention, the study nurse gave the patients information about the procedure,
      discussed strategies they could use to make it as comfortable as possible, and
      explained how they could use a rating scale to denote any physical and emotional
      distress. RESULTS: All patients used the intervention strategies. Three out of
      five reported reduced pain and/or distress following the intervention.
      CONCLUSION: The pilot study supported the use of education as a pain control
      strategy in wound care and illuminated key methodological issues for further
      research on this topic.

PMID- 15160573
TI  - Sponge foam dressing for skin grafting.

PMID- 15160574
TI  - Acceptability to patients of a honey dressing for non-healing venous leg ulcers.
AB  - OBJECTIVES: This four-centre feasibility study was undertaken to determine
      whether Medihoney, a proprietary blend of honeys, is an acceptable treatment for
      patients with leg ulcers in terms of pain relief, odour control and overall
      patient satisfaction. METHOD: Forty patients whose leg ulcers had not responded
      to 12 weeks of compression therapy were recruited. Medihoney dressings were
      applied on their ulcers for the 12-week study period. All other aspects of their
      care, including the use of compression bandaging, remained unchanged. Their leg
      ulcers were assessed every two weeks. This included the use of a patient
      questionnaire. RESULTS: Overall, ulcer pain and size decreased significantly and
      odorous wounds were deodorised promptly. This had a positive impact on patient
      satisfaction with the Medihoney treatment. CONCLUSION: The results support the
      previously reported positive effects of honey and revealed a high patient
      acceptance for this treatment. Following these results, comparative clinical
      trials, which should also consider pain, are now recommended.

PMID- 15160575
TI  - The effects of age-related skin changes on wound healing rates.
AB  - The evidence that wound healing is adversely affected by age-related changes is
      inconclusive. Some studies report that ageing skin loses its ability to
      regenerate, whereas others have found that ageing processes can have beneficial
      effects.

PMID- 15160577
TI  - Our destiny in our hands.

PMID- 15160578
TI  - Experts defend breastfeeding after toxin scare.

PMID- 15160576
TI  - An evaluation of Hyalofill-F plus compression bandaging in the treatment of
      chronic venous ulcers.
AB  - OBJECTIVE: Hyaluronan, a component of the extracellular matrix, plays a
      significant role in several aspects of tissue repair and the wound healing
      process. METHOD: In this Italian study Hyalofill-F, a partial benzyl ester
      derivative of hyaluronan, used in combination with compression bandaging, was
      compared with the well-established therapy in Italy of non-adherent gauze plus
      compression therapy in the treatment of chronic venous leg ulcers. RESULTS:
      Hyalofill-F plus compression bandaging performed significantly better than non
      adherent gauze plus compression bandage in all of the clinically relevant
      efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative
      group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the
      comparator group. The resulting difference of 7.7 cm2 between the two groups was
      statistically significant (p = 0.0019). Furthermore, statistically significant
      results in favour of the hyaluronan-derivative group were obtained in the
      following: speed of epithelialisation; leveling of the margins; degree of
      maceration; pain intensity and frequency. CONCLUSION: Hyalofill-F plus
      compression bandaging resulted in an earlier and greater decrease in ulcer area
      compared with non-adherent gauze plus compression bandaging, therapy supporting
      its use in the treatment of chronic venous ulcers.

PMID- 15160579
TI  - Making ends meet: students and money.

PMID- 15160580
TI  - Common learning and a new generation.

PMID- 15160581
TI  - Thoughts on secondment.

PMID- 15160582
TI  - When understanding saves lives.

PMID- 15160583
TI  - Peri-operative care.
AB  - This is the third 'midwifery basics' series aimed at student midwives, and
      focuses on midwifery care during labour. This article provides a summary of peri
      operative care for women who experience caesarean birth. Students are encouraged
      to seek further information through a series of activities, and to link theory
      with practice by considering the issues relating to the care of the woman
      described in the short vignette.

PMID- 15160584
TI  - Choice, control and the parenting police.

PMID- 15160585
TI  - The travelling midwife.

PMID- 15160586
TI  - Board's eye view.

PMID- 15160587
TI  - Meeting the challenge: an evaluation of the ENP clinic.

PMID- 15160588
TI  - Cranial nerve damage.

PMID- 15160590
TI  - Career mentor.

PMID- 15160589
TI  - Supracondylar fracture of the humerus.

PMID- 15160591
TI  - Beating the bullies.

PMID- 15160592
TI  - Sport performance section.

PMID- 15160593
TI  - Eliminating the dichotomy between theory and practice in talent identification
      and development: considering the role of psychology.
AB  - It is acknowledged that appropriate support and training are essential if
      talented individuals are to fulfil their potential. The early identification of
      talented athletes is an increasingly important consideration for researchers and
      practitioners alike. Once talented individuals have been detected, crucial but
      limited support resources can be optimally deployed to ensure that their needs
      are met and that their gifts are developed. However, there is considerable
      disagreement among experts on what talent is, and which factors can reliably be
      used within talent identification processes. This paper explores prerequisites to
      success in sport, and the comparative efficacy of employing these prerequisites
      within talent identification schemes. It is proposed that talent needs to be
      reconceptualized so that talent identification and talent development processes
      are perceived to be dynamic and interrelated. Additionally, the need to place
      greater emphasis on the capacity of a child to develop in sport and the
      psychological factors that underpin this process is highlighted. To this end, it
      is advocated that talent identification and development schemes, while
      emphasizing the multidimensional nature of talent, need to recognize the
      essential role of psychology in the ability of individuals to fulfil their
      sporting potential.

PMID- 15160594
TI  - Influence of training and match intensity on injuries in rugby league.
AB  - The aim of this study was to examine the influence of perceived intensity,
      duration and load of matches and training on the incidence of injury in rugby
      league players. The incidence of injury was prospectively studied in 79 semi
      professional rugby league players during the 2001 season. All injuries sustained
      during matches and training sessions were recorded. Training sessions were
      conducted from December to September, with matches played from February to
      September. The intensity of individual training sessions and matches was
      estimated using a modified rating of perceived exertion scale. Training load was
      calculated by multiplying the training intensity by the duration of the training
      session. The match load was calculated by multiplying the match intensity by the
      time each player participated in the match. Training load increased from December
      (278.3 [95% confidence interval, CI 262.2 to 294.5] units) to February (385.5
      [95% CI 362.4 to 408.5] units), followed by a decline until September (98.4 [95%
      CI 76.5 to 120.4] units). Match load increased from February (204.0 [95% CI 186.2
      to 221.8] units) to September (356.8 [95% CI 302.5 to 411.1] units). More
      training injuries were sustained in the first half of the season (first vs
      second: 69.2% vs 30.8%, P < 0.001), whereas match injuries occurred more
      frequently in the latter stages of the season (53.6% vs 46.4%, P < 0.001). A
      significant relationship (P < 0.05) was observed between changes in training
      injury incidence and changes in training intensity (r = 0.83), training duration
      (r = 0.79) and training load (r = 0.86). In addition, changes in the incidence of
      match injuries were significantly correlated (P < 0.05) with changes in match
      intensity (r = 0.74), match duration (r = 0.86) and match load (r = 0.86). These
      findings suggest that as the intensity, duration and load of rugby league
      training sessions and matches is increased, the incidence of injury is also
      increased.

PMID- 15160595
TI  - Facilitating effects of exercise on information processing.
AB  - The aim of this study was to examine the facilitating effects of moderate
      physical exercise on the reaction process to gain a better understanding of the
      interaction between physiological and cognitive processes. Sixteen participants
      with specific expertise in decision-making sports performed a double task
      consisting of choice reaction time while cycling. Signal quality, stimulus
      response compatibility and time uncertainty were manipulated. Participants were
      tested at rest and while cycling at 20% and at 50% of their maximal aerobic
      power. A mood assessment questionnaire and a critical flicker fusion test were
      administered before and after the choice reaction time task. The results showed
      that moderate-intensity exercise (50% maximal aerobic power) improves cognitive
      performance and that low-intensity exercise (20% maximal aerobic power) enables
      participants to compensate the negative dual-task effect.

PMID- 15160596
TI  - The relationship of task self-efficacy and role efficacy beliefs to role
      performance in Spanish youth soccer.
AB  - The aim of this study was to examine the relationship between role efficacy and
      role performance after controlling for the effects of task self-efficacy. Two
      hundred and ninety-five Spanish youth soccer players from 20 teams completed self
      report measures of task self-efficacy, role efficacy and role performance at the
      mid-point of a competitive season. The 20 team coaches also provided ratings of
      each of their players' role performances at mid-season. Consistent with
      hypotheses, bivariate correlations showed task self-efficacy and role efficacy
      were positively related to role performance ratings. Hierarchical regression
      analyses revealed that role efficacy contributed significantly to the prediction
      of athletes' ratings of role performance after controlling for task self
      efficacy. Role efficacy also explained significant variation in the prediction of
      coach ratings; however, the effects were less dramatic and inconsistent. Our
      results support self-efficacy theory and reinforce the value of assessing
      efficacy beliefs representing behaviours carried out both independently and
      interdependently for the prediction of role performance within team environments.
      Future research directions are proposed.

PMID- 15160598
TI  - Physiological and metabolic responses of wheelchair athletes in different racing
      classes to prolonged exercise.
AB  - The aims of this study were to examine and compare selected physiological and
      metabolic responses of wheelchair athletes in two paraplegic racing classes [T3:
      n = 8 (lesion levels T1-T7; paraplegics); T4: n = 9 (lesion levels below T7;
      paraplegics)] to prolonged exercise. In addition, we describe the responses of
      three tetraplegic athletes [T2: n = 3 (lesion levels C6/C7: tetraplegics)].
      Twenty athletes completed 90 min of exercise at 75% VO2peak on a motorized
      treadmill adapted for wheelchairs. The mean (+/- s) heart rates of the T3 and T4
      racing classes were 165 +/- 2 and 172 +/- 6 beats.min-1, respectively. For the T4
      racing class, heart rate gradually increased during the test (P < 0.05), whereas
      for the T3 racing class, heart rate reached a plateau after an initial increase.
      The mean heart rate of the tetraplegics was 114 +/- 3 beats.min-1. The T3 and T4
      classes exhibited similar respiratory exchange ratios, plasma lactate and glucose
      concentrations throughout the test. For both the T3 and T4 racing class, free
      fatty acid, glycerol, ammonia, urea and potassium concentrations had increased
      from resting values by the end of the test (P < 0.05). In conclusion, the results
      of this study suggest that endurance-trained wheelchair athletes are able to
      maintain velocities equivalent to the same relative exercise intensity (75%
      VO2peak) for prolonged periods irrespective of lesion level.

PMID- 15160597
TI  - Do handball throws always exhibit a proximal-to-distal segmental sequence?
AB  - Previous studies on overarm throwing have described a proximal-to-distal
      segmental sequence. The proximal segments reached their maximal linear velocities
      before the distal ones. In handball, no study has demonstrated this sequence from
      the upper torso to the wrist, although a recent study did present a different
      organization. The aim of this study was to analyse the throwing arm segmental
      organization during handball throwing. We found that the maximal linear velocity
      of the shoulder occurred after the maximal linear velocity of the elbow.
      Moreover, the maximal angular velocity of the upper torso occurred later than
      that of the elbow. Hence, contrary to other disciplines, the rotation of the
      upper torso was not suddenly stopped just after the forward arm motion was
      initiated. These results may apply to handball in general or be specific to the
      population of handball players studied. It may be advisable in future studies to
      include international players.

PMID- 15160599
TI  - The effect of shaft flexibility on junior golfers' performance.
AB  - The aims of this study were to examine the effect of shaft flexibility on the
      performance of junior golfers and to determine whether there is a relationship
      between golfers' physical characteristics (16 anthropometric measures, age,
      experience, strength), performance and shaft flexibility. We assessed the
      performance of 30 male golfers, aged 7-10 years, with three 7-iron golf clubs of
      different shaft flexibility at a driving range. The performance parameters
      measured for equipment evaluation were ball distance achieved, shot dispersion
      and impact position of the ball on the clubface. The results suggest that there
      is no particular shaft flex suitable for the age group considered and that
      experience, strength and arm span are the significant factors when selecting
      optimal shaft flexibility for children.

PMID- 15160600
TI  - Maximal strength and power, muscle mass, endurance and serum hormones in
      weightlifters and road cyclists.
AB  - Maximal strength, power, muscle cross-sectional area, maximal and submaximal
      cycling endurance characteristics and serum hormone concentrations of
      testosterone, free testosterone and cortisol were examined in three groups of
      men: weightlifters (n = 11), amateur road cyclists (n = 18) and age-matched
      controls (n = 12). Weightlifters showed 45-55% higher power values than road
      cyclists and controls, whereas the differences in maximal strength and muscle
      mass were only 15% and 20%, respectively. These differences were maintained when
      average power output was expressed relative to body mass or relative to muscle
      cross-sectional area. Road cyclists recorded 44% higher maximal workloads,
      whereas submaximal blood lactate concentration was 50-55% lower with increasing
      workload than in controls and weightlifters. In road cyclists, workloads
      associated with blood lactate concentrations of 2 and 4 mmol.l-1 were 50-60%
      higher and occurred at a higher percentage of maximal workload than in
      weightlifters or controls. Basal serum total testosterone and free testosterone
      concentrations were lower in elite amateur cyclists than in age-matched
      weightlifters or untrained individuals. Significant negative correlations were
      noted between the individual values of maximal workload, workloads at 2 and 4
      mmol.l-1 and the individual values of muscle power output (r = -0.37 to -0.49),
      as well as the individual basal values of serum total testosterone and free
      testosterone (r = -0.39 to -0.41). These results indicate that the specific
      status of the participants with respect to training, resistance or endurance is
      important for the magnitude of the neuromuscular, physiological and performance
      differences observed between weightlifters and road cyclists. The results suggest
      that, in cycling, long-term endurance training may interfere more with the
      development of muscle power than with the development of maximal strength,
      probably mediated by long-term cycling-related impairment in anabolic hormonal
      status.

PMID- 15160601
TI  - Light-mediated "conversation" among microorganisms.
AB  - Light emitted from a wide variety of microorganisms was considered previously as
      a waste product. However, it is becoming apparent that it might be involved in
      microbial communication. This paper presents information on such a novel mode of
      communication in different microorganisms.

PMID- 15160602
TI  - Chromium accumulation by living yeast at various environmental conditions.
AB  - Yeast tolerance to Cr (III) and Cr (VI) as well as chromium accumulation
      potential were shown to depend on treatment time, metal concentration, biomass
      density and the phase of growth. Kinetic studies as exemplified by Pichia
      guilliermondii ATCC 201911 revealed a biphasic mode of Cr (III) uptake: a rapid
      sorption phase was followed by a slow process of accumulation, in which the
      contribution of the cell-bound Cr fraction increased, while the total cellular Cr
      level remained constant. Cr (VI) uptake was characterized by a time-dependent
      increase of total Cr and by a constant fractional contribution of the cell
      adsorbed chromium, which suggests that the amount of cell-accumulated Cr also
      tended to increase over time. The resistance to Cr and metal accumulation levels
      were substantially elevated for a given strain when cultures were treated at high
      initial biomass densities (1 mg dry weight/ml) of exponentially proliferating
      cells. Maximum accumulation capabilities ranged between 4.0 and 13 mg Cr (III)/g
      dry weight and 2-6.7 mg Cr (VI)/g dry weight. The total cell-accumulated Cr
      contained 29.3% and 52.3% of organically bound chromium for the treatment of P.
      guilliermondii with Cr (III) and Cr (VI), respectively. Selected yeast strains,
      under specified physiological conditions, can be applied for bioremediation of
      environmental Cr contamination, and might be useful too for attempts to obtain
      chromium-enriched biomass containing biostabilized and nontoxic Cr forms for
      nutritional applications.

PMID- 15160603
TI  - Yeast DNA sequences initiating gene expression in Escherichia coli.
AB  - DNA transfer between pro- and eukaryotes occurs either during natural horizontal
      gene transfer or as a result of the employment of gene technology. We analysed
      the capacity of DNA sequences from a eukaryotic donor organism (Saccharomyces
      cerevisiae) to serve as promoter region in a prokaryotic recipient (Escherichia
      coli) by creating fusions between promoterless luxAB genes from Vibrio harveyi
      and random DNA sequences from S. cerevisiae and measuring the luminescence of
      transformed E. coli. Fifty-four out of 100 randomly analysed S. cerevisiae DNA
      sequences caused considerable gene expression in E. coli. Determination of
      transcription start sites within six selected yeast sequences in E. coli
      confirmed the existence of bacterial -10 and -35 consensus sequences at
      appropriate distances upstream from transcription initiation sites. Our results
      demonstrate that the probability of transcription of transferred eukaryotic DNA
      in bacteria is extremely high and does not require the insertion of the
      transferred DNA behind a promoter of the recipient genome.

PMID- 15160604
TI  - Regulation of pyrimidine nucleotide formation in Pseudomonas taetrolens ATCC
      4683.
AB  - The regulation of the de novo pyrimidine biosynthetic enzymes in the food
      spoilage agent Pseudomonas taetrolens ATCC 4683 was investigated. The de novo
      pyrimidine biosynthetic enzyme activities were determined in P. taetrolens ATCC
      4683 cells and in cells from an auxotroph deficient for orotidine 5'
      monophosphate decarboxylase activity. Pyrimidine supplementation to the culture
      medium affected the biosynthetic enzyme activities in ATCC 4683 cells.
      Transcriptional regulation of the biosynthetic pathway by pyrimidines was
      indicated after the auxotroph was subjected to pyrimidine limitation. At the
      level of enzyme activity, aspartate transcarbamoylase activity was strongly
      inhibited by pyrophosphate, ADP, ATP, UDP, UTP and GTP. Transcriptional
      regulation of pyrimidine synthesis in P. taetrolens was not as highly controlled
      as in the taxonomically-related species Pseudomonas fragi although both species
      contained transcarbamoylase activities subject to significant nucleotide
      inhibition.

PMID- 15160605
TI  - Effect of preculturing conditions on growth of Lactobacillus rhamnosus on medium
      containing glucose and citrate.
AB  - Lactobacillus rhamnosus can metabolize citrate through a citrate inducible
      transport system. The growth curves of L. rhamnosus on medium containing glucose
      and citrate was found to be highly dependent on preculturing conditions. It
      exhibited diauxic growth when precultured on glucose, but demonstrated
      simultaneous consumption when cultured on citrate. The maximum specific growth
      rate for cells growing on glucose + citrate was 0.38 h-1, which was higher than
      the growth rate on individual substrates (0.28 h-1). Simultaneous consumption
      also yielded higher net flavour compounds, diacetyl and acetoin. Flux analysis
      indicated that L. rhamnosus requires oxygen for balancing excess NADH through
      NADH oxidase. The flux analysis provided insights into the metabolic network of
      L. rhamnosus.

PMID- 15160606
TI  - Detection and molecular characterization of an aster yellows phytoplasma in poker
      statice and Queen Anne's lace in Alberta, Canada.
AB  - Queen Anne's lace and poker statice plants were found with a yellows-type disease
      with typical phytoplasma symptoms in an experimental farm near Brooks, Alberta in
      1996. Phytoplasma bodies were detected by transmission electron microscopy in
      phloem cells of symptomatic plants, but not in healthy plants. The presence of a
      phytoplasma was confirmed by analysis with the polymerase chain reaction. Using a
      pair of universal primer sequences derived from phytoplasma 16S rRNA, an
      amplified product of the expected size (1.2 kb) was observed in samples from
      infected plants, but not in asymptomatic plants. Sequence analysis of the PCR
      products from the 16S/23S rDNA intergenic spacer region indicated that the two
      phytoplasma isolates in Queen Anne's lace and poker statice are genetically
      closely related to the western aster yellows phytoplasma.

PMID- 15160607
TI  - Resistance of spheroplasts and whole cells of Pseudomonas aeruginosa to
      bactericidal activity of various biocides: evidence of the membrane implication.
AB  - To emphasise the role of outer and inner membranes in the resistance of
      Pseudomonas aeruginosa to bactericidal activity of various disinfectants,
      spheroplasts and whole cells were compared. Spheroplasts are more sensitive than
      whole cells to quaternary ammonium compounds such as didecyl dimethyl ammonium
      bromide (DDAB) and C16-benzalkonium chloride. The outer membrane acts as a
      barrier to prevent these disinfectants from entering the cell. It seems to have
      no influence on activities of smaller molecules such as C12, C14-benzalkonium
      chlorides and sodium dichloroisocyanurate. For tri-sodium phosphate, the presence
      of outer membrane emphasized the action of the molecule. Moreover, resistance of
      DDAB-adapted spheroplasts to bactericidal activity of DDAB is higher than the
      resistance of non-adapted spheroplasts. This suggests that the inner membrane
      could also play a role in resistance to DDAB.

PMID- 15160608
TI  - Isolation, geographical diversity and insecticidal activity of Bacillus
      thuringiensis from soils in Spain.
AB  - Bacillus thuringiensis is a spore-forming bacterium showing the unusual ability
      to produce endogenous crystals during sporulation that are toxic for some pest
      insects. This work was performed to study the composition, ecological
      distribution and insecticidal activity of isolates of this entomopathogenic
      bacterium from the Spanish territory. Using a standard isolation method, B.
      thuringiensis was isolated from 115 out of 493 soil samples collected in the
      Iberian Peninsula and the Canary and Balearic Archipelagos. The percentages of
      samples with B. thuringiensis were 31.7, 27.6 and 18.5 and the B. thuringiensis
      index 0.065, 0.067 and 0.11 for the Iberian Peninsula, Canary and Balearic
      Archipelagos, respectively. The prairies were shown to be the worst source of B.
      thuringiensis while forests, urban and agricultural habitats showed similar
      percentages. Strain classification based on H-antigen agglutination showed a
      great diversity among the Spanish isolates, which were distributed among 24
      subspecies, including three new ones andaluciensis, asturiensis and
      palmanyolensis. We differentiated 65 different protein profiles of spore-crystal
      mixtures by sulfate-polyacrylamide gel electrophoresis and we selected 109
      isolates representative of these profiles to evaluate their insecticidal activity
      against insects from the Orders Orthoptera, Dictyoptera, Coleoptera, Lepidoptera
      and Diptera. We found variable percentages of isolates active against Coleoptera
      and Lepidoptera, one isolate highly active against mosquito larvae and for the
      first time, three isolates active against cockroaches and locusts.

PMID- 15160609
TI  - Involvement of secondary metabolites and extracellular lytic enzymes produced by
      Pseudomonas fluorescens in inhibition of Rhizoctonia solani, the rice sheath
      blight pathogen.
AB  - Fourteen strains of Pseudomonas fluorescens isolated from rhizosphere soil of
      rice were tested for their antagonistic effect towards Rhizoctonia solani, the
      rice sheath blight fungus. Among them, PfMDU2 was the most effective in
      inhibiting mycelial growth of R. solani in vitro. Production of chitinase, beta
      1,3-glucanase, siderophores, salicylic acid (SA) and hydrogen cyanide (HCN) by P.
      fluorescens strains was evaluated. The highest beta-1,3-glucanase activity,
      siderophore production, SA production and HCN production were recorded with
      PfMDU2. A significant relationship between the antagonistic potential of P.
      fluorescens against R. solani and its level of beta-1,3-glucanase, SA and HCN was
      observed.

PMID- 15160611
TI  - Changes in whole cell-derived fatty acids induced by naphthalene in bacteria from
      genus Pseudomonas.
AB  - Fatty acid composition during naphthalene utilization was investigated in three
      strains of bacteria Pseudomonas vesicularis, Pseudomonas stutzeri and Pseudomonas
      sp. JS150 that expressed different naphthalene degradation abilities. All strains
      significantly changed their cellular fatty acid profiles as a response to
      naphthalene exposure. Since naphthalene was present in the medium P. stutzeri
      increased ratio of saturated/unsaturated fatty acids from 1.1 to 2.1 and
      Pseudomonas sp. JS150 from 7.5 to 12.0, respectively. In contrast, this ratio
      decreased from 2.1 to 1.1 in P. vesicularis under the same growth conditions. The
      changes comprised also alterations in the percentage of selected groups of fatty
      acids: iso and anteiso, hydroxy and cyclopropane fatty acids. Our results showed
      that naphthalene induced in tested strains different changes in fatty acids
      composition. It may suggest that in the presence of naphthalene microorganisms
      used different adaptive mechanisms to maintain the cells in appropriate
      physiological state.

PMID- 15160610
TI  - Purification of the extracellular pectinolytic enzyme from the fungus Rhizopus
      oryzae NBRC 4707.
AB  - The pectinolytic enzyme from the solid-state culture of Rhizopus oryzae NBRC 4707
      was purified to homogeneity by column chromatography on CM-Toyopearl 650 M and
      hydroxylapatite. The molecular weight of the enzyme was estimated by SDS
      polyacrylamide gel electrophoresis to be 31,000 and was reduced to 29,700 after
      treatment with endoglycosidase H. Maximal activity was observed near pH 4.5 at 45
      degrees C. The enzyme was shown to be endopolygalacturonase, as judged from the
      formation of oligogalacturonides as its reaction products. The addition of
      purified enzyme, as expected, enhanced the formation of lactic acid and ethanol
      in potato pulp grown with R. oryzae.

PMID- 15160612
TI  - Buruli ulcer disease.

PMID- 15160613
TI  - Children and choice.

PMID- 15160615
TI  - Working together with diabetes.

PMID- 15160616
TI  - Deciding on MMR.

PMID- 15160614
TI  - Prevention of sore heels: evidence and outcomes.

PMID- 15160617
TI  - Leadership in children's nursing: impact on policy.

PMID- 15160618
TI  - Statistics made simple. Part 1. Mean, medians and modes.

PMID- 15160620
TI  - Care protocols: rigid rules or useful tools?

PMID- 15160619
TI  - Teaching young children about cystic fibrosis.

PMID- 15160621
TI  - Use of the Glasgow coma scale in infants.

PMID- 15160622
TI  - Maternity services are failing deaf women.

PMID- 15160623
TI  - Healthy Start: the latest proposals.

PMID- 15160624
TI  - Helping children with learning disabilities. Making sense of multisensory
      environments.
AB  - Multisensory environments are specially designed to enable individuals with
      learning disabilities to enjoy a wide range of sensory experiences. The author, a
      lecturer in occupational therapy, outlines the history and features of
      multisensory environments. Using two case studies, he illustrates how they can be
      used in successful therapeutic interventions. The article reviews the function of
      multisensory environments for children with learning disabilities.

PMID- 15160625
TI  - Health and nutrition series--2. What do we know about ... diet and cardiovascular
      disease?

PMID- 15160626
TI  - Continence and children: what progress?

PMID- 15160627
TI  - Postnatal depression.

PMID- 15160628
TI  - Infantile colic.
AB  - Infantile colic is a common problem, but it is still a cause of great stress and
      anxiety to the parents of a colicky baby. Dipak Kanabar believes that failure of
      lactose digestion has an important part to play in colic and in this bulletin he
      reviews the causes of infantile colic and the available management options.

PMID- 15160629
TI  - Breastfeeding--aim for comfort.
AB  - There is now little disagreement that 'breast is best'. The health benefits for
      both mother and child are undisputed, and the latest UK Department of Health
      recommendations are that breastfeeding should be the exclusive form of infant
      nutrition for the first six months of life. So why are only a fifth of mothers
      still breastfeeding at six months, and why is there such a rapid decline in
      breastfeeding in the first few weeks?

PMID- 15160630
TI  - The nursing leadership program. The Cyprus experience--a tale of two cultures.
AB  - Implementing a leadership program in a distant and culturally unique country
      poses numerous challenges and a terrific opportunity to develop cultural
      awareness and competence. The political history of Cyprus provides a context for
      understanding the delicate balance that Duke University School of Nursing faculty
      had to maintain throughout the offering of a leadership program that was funded
      through a United States Congressional program of Economic Support Funds (ESF).
      Although participants were all nurses and all Cypriots, they represented two very
      different cultures, languages, governments, and health care systems. These
      differences had to be addressed on every level, ranging from the food served and
      the language spoken in the conference to the need for impartiality when working
      with participants.

PMID- 15160631
TI  - The NIA Group. Building a sense of purpose in preadolescent African American
      girls: a novel approach to nursing leadership in community health.
AB  - Many African American girls experience pubertal development early. Earlier
      pubertal development may place these girls at greater risk of exposure to or
      engagement in early sexual behavior. Young girls facing this societal context
      need interventions to help them develop healthy self-esteem, pride in their
      cultural heritage, good decision-making skills and a sense of purpose. It was
      from these concerns that the NIA Program of Self-Development for preadolescent
      girls was initiated as a collaboration of the University of Pittsburgh School of
      Nursing, a local public school, and the nursing staff of the Matilda Theiss
      Health Center, a comprehensive community health center that houses the NIA Group.
      The group's name, "NIA," meaning a sense of purpose, is derived from one of the
      seven principles of Kwanzaa, a yearly African American celebration of cultural
      heritage.

PMID- 15160632
TI  - Freshman seminars. Do they help pre-nursing students adjust to college life?
AB  - One purpose of this phenomenological study was to identify challenges pre-nursing
      students face as they enter college. A second purpose was to evaluate the
      effectiveness of a Freshman seminar in helping students develop a sense of
      belonging on campus. An interpretive analysis was completed of 20 student essays
      focused on these challenges and the effectiveness of the Freshman seminar.
      Students reported that three major challenges confronted them as they
      transitioned from high school to college. These challenges were to "make the
      space on campus my own," "get used to the way things are done in college," and
      "get a sense of who I really am." The Freshman seminar helped pre-nursing
      students settle into a new environment and better prepare themselves for nursing
      school. Strategies used in the freshman seminar are also applicable to service
      delivery settings.

PMID- 15160633
TI  - Staff nurse retention. Laying the groundwork by listening.
AB  - In response to critical staff shortages, the nursing leadership of a five
      hospital system implemented a research program to create a health promoting
      organization that would support nurse retention. Since a health promoting
      organization supports each individual's participation in the decision-making
      process through communication and consensus-building, listening to the concerns
      of current nurse managers (Parsons & Stonestreet, 2003) and staff nurses was
      crucial for developing innovative retention strategies. This qualitative study
      utilized open-ended, data-generating questions in focus groups to elicit the
      issues staff nurses considered crucial to their continued employment. Consistent
      with findings in the literature, the quality of administrative management systems
      and relationships with physicians, nurse managers, peers, and administrators were
      essential factors for nurse retention in this system.

PMID- 15160634
TI  - Interview with Eleanor K. Herrmann, EdD, RN, FAAN. Interview by Sandra B.
      Lewenson.

PMID- 15160635
TI  - Introduction: motivation, drug abuse, and 50 years of theoretical and empirical
      inquiry.

PMID- 15160636
TI  - Allostatic view of motivation: implications for psychopathology.

PMID- 15160637
TI  - Dual determinants of drug use in humans: reward and impulsivity.

PMID- 15160638
TI  - Triggers of relapse: nonhuman primate models of reinstated cocaine seeking.

PMID- 15160639
TI  - The role of emotional systems in addiction: a neuroethological perspective.

PMID- 15160640
TI  - Biological connection between novelty- and drug-seeking motivational systems.

PMID- 15160641
TI  - Drive, incentive, and reinforcement: the antecedents and consequences of
      motivation.

PMID- 15160642
TI  - Pathways to relapse: factors controlling the reinitiation of drug seeking after
      abstinence.

PMID- 15160643
TI  - Drugs, behavior, and environmental sources of motivation: bridging a gap.

PMID- 15160644
TI  - [Seborrheic dermatitis: frequent, but unknown].

PMID- 15160645
TI  - [Epidemiology of seborrheic dermatitis].

PMID- 15160646
TI  - [Pathogenesis of seborrheic dermatitis].

PMID- 15160647
TI  - [Seborrheic dermatitis in the child].

PMID- 15160648
TI  - [Clinical presentation in the adult].

PMID- 15160649
TI  - [Treatment of seborrheic dermatitis].

PMID- 15160650
TI  - Yale Child Study Center and child psychiatry in Israel--a history of a special
      bond.

PMID- 15160651
TI  - The Bioethics of Children's Rights.
AB  - The Bioethics of Children's Rights are not only embedded in child development
      knowledge and in the laws of a particular nation or society, but also in the
      values, customs and practices of the culture in which they are formulated and
      practiced. The Bioethics of Children's Rights reflect the changing values
      assigned to children by adults in our society and are determined by the parents
      or parental adults responsible for the care and safety of children. The Bioethics
      of Children's Rights reflect the role of children of different ages in a
      particular society and community. It is difficult to conceptualize and define. It
      is fundamental to realize that you cannot refer to children's rights without
      taking into account the adults who provide them with the continuity of their
      affectionate, safe-guarding care. It is the parent(s) or their surrogates who
      have the capacity, authority and responsibility for defining those rights, and
      for asserting and assuring they are in the service of their children's needs and
      priorities. This paper, using case vignettes, is intended to heighten our
      consciousness that by and large children are unable to speak effectively for
      their rights alone. Through the voices of their parents, care-providers and the
      society in which they live, we can examine the voice of the child, with the
      child's needs and potentialities being paramount.

PMID- 15160652
TI  - Psychopharmacology and psychoanalysis.
AB  - Mood disease results from impaired mood regulation. Mood is a direct function of
      libido, and that is probably a function of the activity of the seeking system.
      The neurotransmitters that are provided by current medication for mood disorder
      influence this system and are used to overcome excursions that transgress either
      the manic or the depressive boundaries of the normal envelop of variation, and
      with greater difficulty to overcome the excessive mood volatility of the disease
      syndromes associated with rapid cycling. Psychoanalytic sensitivity to the
      indications of mood in session contents and dreams can guide drug monitoring and
      adjustment.

PMID- 15160653
TI  - Attitudes toward Arabs of Israeli children exposed to missile attacks: the role
      of personality functions.
AB  - BACKGROUND: This study examines the attitudes toward Arabs of Israeli children
      who were exposed to missile attacks during the Gulf War as related to exposure,
      early and present functioning, and appraisal of chances for peace. METHODS: A
      semi-structured interview assessed the attitudes, symptoms, defenses and
      prosocial behavior of 82 children who had been directly exposed to the missile
      attacks. RESULTS: The attitudes were not related to the displacement of the
      family during the war. A very negative attitude was associated with more problems
      with behavior modulation during the preschool years, an increase in externalizing
      and posttraumatic symptoms, and more immature defenses. A balanced attitude was
      associated with age, fewer symptoms, more mature defenses, and more prosocial
      behavior. CONCLUSION: Individual vulnerabilities in the face of traumatic
      experiences could lead to posttraumatic responses that may shape children's
      social attitudes and behaviors. The resolution of inter-group conflict requires
      implementation of psychotherapeutic and socio-educational interventions to
      transform hate and fear into empathy and hope.

PMID- 15160654
TI  - The Military Life Scale: a measure of perceived stress and support in the Israeli
      Defense Force.
AB  - GOALS: The purpose of this study was to construct a reliable and valid measure of
      perceived stress and support by adolescents in the Israeli military, and to
      explore its structure and psychometric properties. METHOD: A large stratified
      sample of soldiers, representing different types of units, different lengths of
      service in the Israel Defense Force, and different ranks, were administered the
      Military Life Scale. Principal component factor analysis with varimax rotation
      resulted in a 5-factor structure for the stress scale, and a 5-factor structure
      for the support scale. RESULTS: All factor-derived scales showed satisfactory
      scale reliability and discriminant validity. CONCLUSIONS: The Military Life Scale
      is useful for measuring the stress experienced by individuals and groups within
      the Israel Defense Force. In addition, the Military Life Scale may be of use in
      other military environments, and with minor revision, in non-military
      environments in which the normative passage from late adolescence into adulthood
      occurs, such as a college setting.

PMID- 15160655
TI  - An autonomic nervous system biofeedback modality for the treatment of attention
      deficit hyperactivity disorder--an open pilot study.
AB  - OBJECTIVE: To study the effect of a new non-invasive technique of non-cognitive
      biofeedback called Autonomic Nervous System Biofeedback Modality on the
      behavioral and attention parameters of a sample of children with attention
      deficit hyperactivity disorder. METHOD: 19 subjects attending regular schools,
      who met DSM-IV criteria for attention deficit hyperactivity disorder, received
      four sessions of Autonomic Nervous System Biofeedback Modality treatment. The
      heart rate variability was measured before and after the treatment, as were
      measures of efficacy including Conners' Teacher Questionnaires (28 items), the
      Child Behavior Check List for parents and teachers and Continuous Performance
      Test. RESULTS: Positive treatment effect was observed in all the subjects. The
      parent's Child Behavior Check List and Conners' Teacher Questionnaires of the
      whole group showed statistically significant differences. The teacher's Child
      Behavior Check List showed positive change not reaching statistical significance.
      A positive correlation between heart rate variability changes and improvement of
      symptoms of attention deficit hyperactivity disorder was found. CONCLUSION: These
      are preliminary findings of apparent efficacy of Autonomic Nervous System
      Biofeedback Modality treatment for attention deficit hyperactivity disorder in
      children. Future controlled trials are warranted.

PMID- 15160656
TI  - Schizophrenia in adolescent twins: a case study.
AB  - Studies of schizophrenia in twins have historically influenced the psychiatric
      world in shifting the focus of the etiology of psychiatric disorders from a
      psychodynamic to a genetic one. Although twinning is as frequent a phenomenon as
      schizophrenia, clinical issues relating to the development of twins and treatment
      of psychiatrically sick twins are relatively infrequent in the literature. This
      article presents the treatment of adolescent schizophrenic twins, and focuses on
      specific developmental, educational and therapeutic issues that must be
      considered when treating twins. The recent treatment of identical schizophrenic
      twins has allowed us to review the literature and revisit some of these issues.

PMID- 15160657
TI  - When patients run the show: the Sderot Psychiatric Center's Puppet Theater.
AB  - Psychiatric rehabilitation combats the damaging effects of mental illness on
      living, occupational and social skills, and strives to help patients lead
      creative and fulfilling lives. Medical and social changes, as well as financial
      pressure, have all increased the need for community rather than institutional
      rehabilitation. New philosophical emphases highlight patient self-actualization
      and empowerment. This paper describes the development of a puppet theater, whose
      members and artistic director are almost all chronic psychiatric patients; the
      project has achieved steady sheltered employment status and been awarded the
      first Zussman-JDC prize by the president of Israel. Interviews with patients
      elicited major differences between patient perceptions of traditional
      rehabilitation frameworks and the theater. Theater is more creative than typical
      sheltered employment opportunities for mental patients, and puppet theater has
      unique aspects that may be especially suited to their needs. Patients found
      participation an empowering experience.

PMID- 15160658
TI  - The gardener and the dinosaur: remembering Zayde.

PMID- 15160659
TI  - Early infantile autism and fragile X anomaly.

PMID- 15160660
TI  - Olanzapine for childhood disintegrative disorder.

PMID- 15160661
TI  - The American Society of Pediatric Hematology/Oncology Distinguised Career Award
      goes to Anna T. Meadows, M.D.

PMID- 15160662
TI  - [Autoregulation of dynamic cerebral blood flow during hypotensive anesthesia with
      prostaglandin E1 or nitroglycerin].
AB  - BACKGROUND: Autoregulation of dynamic cerebral blood flow during hypotensive
      anesthesia is unclear. We examined the effects of hypotensive anesthesia with
      prostaglandin E1 (PGE1) or nitroglycerin (NTG) on autoregulation of the dynamic
      cerebral blood flow. METHODS: Beat-by-beat mean arterial pressure (MAP) and blood
      flow velocity in the middle cerebral artery were measured before and during
      hypotensive anesthesia. The relationship between changes in MAP and cerebral
      blood flow velocity was evaluated by using the method of transfer function
      analysis. We calculated transfer function gain and coherence by cross-spectrum
      from autospectra of MAP and blood flow velocity in the low (0.07-0.2 Hz) and high
      (0.2-0.3 Hz) frequency ranges. RESULTS: The gain in the both frequency ranges was
      unchanged during hypotensive anesthesia with PGE1. During hypotensive anesthesia
      with NTG, the gain in the high frequency range was unchanged, either. However,
      the gain in the low frequency range increased during hypotensive anesthesia with
      NTG. The value was significantly higher than in hypotensive anesthesia with PGE1.
      CONCLUSIONS: These results suggest that hypotensive anesthesia with PGE1
      maintains autoregulation of the dynamic cerebral blood flow, but NTG impairs the
      autoregulation in the low frequency range.

PMID- 15160663
TI  - [Colforsin daropate does not affect the cerebral blood-flow in cardiac surgery
      patients under cardiopulmonary bypass].
AB  - BACKGROUND: Cerebral blood flow partly plays a pivotal role in cerebral
      complications among cardiac surgery patients. We evaluated the effect of
      colforsin daropate (colforsin) on cerebral blood flow in cardiac surgery patients
      under cardiopulmonary bypass (CPB) by transcranial Doppler sonography (TCD).
      METHODS: Eighteen patients scheduled for coronary artery bypass surgery under CPB
      were assigned randomly to two groups:colforsin group (n=9) and control group
      (n=9). We assessed cardiac function by measuring cardiac index (CI) and systemic
      vascular resistance index (SVRI). Cerebral blood flow was evaluated by measuring
      the peak systolic blood flow velocity (Vs), end-diastolic blood flow velocity
      (Vd) together with mean blood flow velocity (Vm), and calculated the pulsatility
      index (PI) in the left carotid siphon by TCD. After baseline measurement, the
      colforsin loading dosage was increased from 0.25 to 0.5 microg x kg(-1) x min(-1)
      in colforsin group every 60 minutes. RESULTS: Colforsin significantly increased
      CI and decreased SVRI compared with pre-levels. In both groups there were no
      significant changes in Vs, Vd, Vm and PI. CONCLUSIONS: We have demonstrated that
      colforsin is effective for hemodynamics without cerebral blood flow change in
      cardiac surgery patients under cardiopulmonary bypass.

PMID- 15160665
TI  - [Cauda equina syndrome following intrathecal dibucaine].
AB  - We report three cases of cauda equina syndrome following spinal anesthesia with
      dibucaine. In two cases, the lumbar puncture was repeated and additional doses of
      dibucaine were administered to obtain adequate sensory blockade. In the last
      case, spinal anesthesia worked well with single injection of dibucaine. In all
      cases patients complained of varying degrees of bladder and bowel dysfunction,
      perineal sensory loss and lower extremity motor weakness on the next day, and the
      diagnosis of cauda equina syndrome was made. With only one case, the symptom
      disappeared four months later, but the rest of the patients suffered from sensory
      disturbance and defecation for more than four months after the surgery. One
      possible cause is a direct neurotoxic effect of high concentration dibucaine due
      to its maldistribution within the subarachnoid space. We have to consider the
      neurotoxicity and dose of the local anesthetic for obtaining a safer method and
      for preventing this complication.

PMID- 15160664
TI  - [Pain control with epidural anesthesia for uterine artery embolization].
AB  - BACKGROUND: To reduce the severity of post procedure pain associated with uterine
      artery embolization (UAE) for leiomyomata, we used continuous infusion of low
      concentration ropivacaine through an epidural catheter. METHODS: Thirteen
      patients for UAE were evaluated. In a patient without indication for epidural
      anesthesia, the pain was controlled with intermittent morphine infusion. Other
      patients had post procedure pain managed with 10 ml bolus of 1% lidocaine and
      continuous infusion of 0.2% ropivacaine at 5 ml x hr-1 for 16 hours. RESULTS: The
      patient complained of severe pain just after UAE and required epidural lidocaine.
      Then, we started to infuse lidocaine or ropivacaine just before starting UAE.
      Among these cases, 9 patients required extra pain control using NSAIDs as a
      rescue. Only three patients required no medication except epidural analgesia.
      CONCLUSIONS: Continuous infusion of 0.2% ropivacaine at a rate of 5 ml x hr-1 is
      not enough for pain management after UAE.

PMID- 15160666
TI  - [Anesthetic management with total intravenous anesthesia for a patient with
      previous history of acute myocarditis].
AB  - Myocarditis is often self-limited and without sequelae, most commonly the result
      of the viral infection. Recently it has been pointed out that there are some
      cases of myocarditis progressing to a chronic phase like dilated cardiomyopathy.
      Worsening congestive heart failure and findings of new electrocardiographic
      changes are the most catastrophic, sometimes fatal, perioperative events. We
      experienced a case of a 45-year-old woman with previous history of idiopathic
      acute cardiomyopathy for non-cardiac surgery. For electrocardiogram monitoring, a
      five-lead system to detect the intraoperative ischemic events was used to detect
      frequent ST-T-wave abnormalities. Reducing cardiac irritability and preventing
      infection are the main points for this anesthetic management. We gave general
      anesthesia, not combining with epidural anesthesia, to avoid epidural abscess
      which may cause recurrence of myocarditis. We employed total intravenous
      anesthesia (TIVA) technique using propofol administration with TCI system and
      repetitive fentanyl injections. Propofol target concentration was titrated
      according to bispectral index (BIS) between 40-60. The patient emerged quite well
      within 20 minutes after discontinuing propofol. We could maintain hemodynamics
      stably and no severe adverse effects were observed perioperatively. Thus this
      anesthesia technique was safe and useful to maintain the hemodynamics stably in
      the case with previous history of idiopathic acute cardiomyopathy.

PMID- 15160667
TI  - ["Takotsubo" cardiomyopathy developed in the postoperative period in a patient
      with amyotrophic lateral sclerosis].
AB  - A 75-year-old woman with amyotrophic lateral sclerosis (ALS) underwent surgical
      gastrostomy and repair of incisional hernia. Anesthesia was induced with propofol
      and high concentrations of sevoflurane. Tracheal intubation was performed without
      muscle relaxants. Anesthesia was maintained with sevoflurane and thoracic
      epidural anesthesia (bupivacaine and fentanyl). Surgery, emergence and extubation
      were completed uneventfully. She was transferred to ICU for postoperative
      observation. On the 2 nd POD, however, she was re-intubated due to sudden dyspnea
      and desaturation caused by failed sputum exhaustion. Simultaneously, her ECG
      showed ischemic change in leads I, III, aVF, and V3-6. Left ventriculogram showed
      an "Ampulla" or so called "Takotsubo" shape with intact coronary angiogram. After
      medication with nitroglycerin and diltiazem, her ECG returned to normal. She
      showed no deterioration of neurological symptoms. No respiratory and cardiac
      events were reported until her discharge from hospital. We conclude that an
      extreme care is required in patient with ALS to avoid perioperative
      complications.

PMID- 15160668
TI  - [Brachial plexus neuropathy following open-heart surgery].
AB  - A 64-year-old woman underwent open-heart surgery for repair of atrial septal
      defect (ASD) and tricuspid valve regurgitation. Preoperative complications
      included rheumatoid arthritis with pain in both wrists treated with methotrexate.
      Following smooth endotrachial intubation, a pulmonary arterial (PA) catheter was
      inserted into the right jugular vein after several attempts. She was placed in a
      supine position with abduction of the shoulders to approximately 90 degrees and
      of the elbows to 60 degrees. Operation was performed through sternum splitting to
      second intercostal space, and the 4-h intraoperative course was uneventful. On
      the first postoperative day, she complained of inability to raise her right arm.
      Neurological examination revealed marked weakness of the deltoid and biceps
      brachialis muscles, and decreased sensitivity around the right shoulder.
      Iatrogenic brachial plexus injury was diagnosed. Administration of vitamin B12
      and physical therapy were instituted. Symptoms improved gradually and had
      disappeared by 3 months postoperatively. Neuropathy might be attributed to
      stretch and compression of the brachial plexus caused by traction of the
      pectoralis minor muscle enhanced by sternotomy and/or malposition of the upper
      extremity, or direct injury due to cannulation of the PA catheter into the
      internal jugular vein.

PMID- 15160669
TI  - [Clinical experience of landiolol for the treatment of intraoperative rapid
      atrial fibrillation].
AB  - A 79-year-old woman with three vessel disease and mitral as well as tricuspid
      regurgitation underwent operation twice. Preoperatively she had atrial
      fibrillation and heart failure. The first operation was coronary artery bypass
      grafting (CABG), and the second was mediastinal dissection for mediastinitis one
      month after the CABG. In both operations she developed rapid atrial fibrillation
      and ventricular fibrillation, showing her cardiac irritablility. Both operations
      were performed under cardiopulmonary bypass and support. In the first operation
      digoxin and verapamil partly reduced heart rate of rapid atrial fibrillation from
      140-170 to 110-140 beats x min-1, which made us use another drug, a short acting
      selective beta 1 blocker landiolol in the second operation. Landiolol
      successfully reduced the heart rate of rapid atrial fibrillation from 140-160 to
      80-90 beats x min-1. This case demonstrates that landiolol can be safely used in
      a patient with heart failure due to rapid atrial fibrillation resistant to
      digoxin and verapamil.

PMID- 15160670
TI  - [Successful pain control by continuous epidural infusion of ropivacaine for a
      pregnant woman with biliary colic].
AB  - This report describes a pregnant woman with common bile duct stones whose colic
      was successfully treated by prolonged continuous epidural infusion of
      ropivacaine. A 32-year-old woman in the 26th week pregnancy complained of severe
      abdominal pain due to common bile duct stones. We adopted ropivacaine for
      infusion into the epidural space using patient controlled analgesia system
      considering fetoplacental circulation. We administered the solution successfully
      for 3 weeks, but we observed that the effectiveness of ropivacaine became
      reduced. This suggests that tachyphilaxis to ropivacaine might have developed by
      its long-term infusion.

PMID- 15160671
TI  - [Anesthetic management for laparoscopic repair of Morgagni-Larry hernia in a
      child].
AB  - A 5-year-old asymptomatic boy was shown to have bowel loops in the thoracic
      cavity incidentally in a chest radiograph. A barium swallow confirmed the
      diagnosis of Morgagni hernia. Laparoscopic repair under CO2 pneumoperitoneum was
      performed. Anesthesia was induced and maintained with air, oxygen and
      sevoflurane. After pulling the transverse colon and the greater omentum into the
      abdomen, it was found that a part of the liver was also herniated into the right
      sternocostal hiatus (Larry hernia). The patient showed uneventful recovery.
      However, we should realize that dissection of adhesions between the viscera and
      peritoneal sac may be dangerous with possibility of pneumomediastinum or
      pneumothorax under pneumoperitoneum.

PMID- 15160672
TI  - [A case of Churg-Strauss syndrome undergoing cesarean section].
AB  - A 37-year-old woman with Churg-Strauss syndrome underwent cesarean section under
      combined spinal-epidural anesthesia. Churg-Strauss syndrome is a rare diffuse
      vasculitis accompanied by severe asthma. Anesthesia was performed uneventfully,
      but there were several issues of concern regarding the perioperative management
      of this syndrome.

PMID- 15160674
TI  - [Evaluation by undergraduate medical students of clinical clerkships in the
      Department of Anesthesiology].
AB  - BACKGROUND: Clerkships for undergraduate clinical training were introduced in
      Sapporo Medical University School of Medicine in 2002. METHODS: Questionnaire
      surveys by 5 steps Likert measure were conducted by asking the students about the
      evaluation of each department or division, and overall evaluation was obtained
      after the clerkships. The questionnaire consisted of 12 questions on 1)
      orientation; 2) learning chances and provision of teaching materials; 3)
      feedback, learning promotion and teaching attitude; 4) coordination of human
      relationship between medical staff and students; and 5) overall evaluation of
      teacher's physician. RESULTS: The average score for our department was 4.30
      (mean, 6th grade of all 26 departments/divisions), and the scores on provision of
      medical practice (4.69) and the overall teacher's physician grading (4.65) were
      the best among the all departments/divisions. The evaluation gradings were rather
      low on chances for medical and health care interviews (3.59); physical
      examinations (3.83); and description of medical record (3.73). CONCLUSIONS:
      Reevaluation of the educational program in our department based on the results of
      the survey is essential for improvement of the program, and further provision of
      chances, especially for medical interviews, physical examinations and description
      of medical record is also needed for undergraduate students in the program.

PMID- 15160675
TI  - [Hospital no-smoking policy could increase smoking cessation rate among
      preoperative patients].
AB  - BACKGROUND: Although it is well known that a no-smoking policy can reduce smoking
      rate among hospital employees, the effect of this policy on patients' smoking
      behavior has not been examined. METHODS: Starting on the world no-tobacco day in
      2001, the Sakai Municipal Hospital changed partial no-smoking policy into
      complete no-smoking policy. In this study, we examined the effect of this policy
      change on patients' smoking status during preoperative period. At preoperative
      visit, we asked a patient a change of smoking status during preoperative period.
      The change of patients' smoking status was compared between before and after
      coming into effect of no-smoking policy. RESULTS: Smoking rates at first visit to
      out-patient clinic of each surgical department before and after coming into
      effect of no-smoking policy were 35.6%(36/101) and 41.8%(28/67), respectively
      (P=0.317). Among these smokers, smoking cessation rates at preoperative visit
      before and after coming into effect of no-smoking policy were 44.4%(16/36) and
      75.0%(21/28), respectively (P=0.014). CONCLUSIONS: The hospital no-smoking policy
      has a strong effect on improvement of patients' smoking behavior during
      preoperative period.

PMID- 15160673
TI  - [Appropriate evaluation of total workload in anesthesia].
AB  - Number of cases performed or total anesthesia time is usually used to evaluate
      workload anesthesiologists. However, each case is different in intensity of
      anesthetic management and these makes the evaluation difficult. We devised a
      total workload in anesthesia formula to account for technical, tactical, and
      physical factors in each case, as well as for number of cases and total
      anesthesia time. The present study evaluated reasonableness of this formula. We
      compared number of cases, hours of work, medical treatment fee and the total
      workload in anesthesia among anesthesiologists who had worked in our hospital in
      2001. Each anesthesiologist answered questionnaires regarding number of cases,
      total anesthesia time, and total workload during 2001. Among anesthesiologists,
      we found significant differences in number of cases and total anesthesia time and
      medical treatment fee but no difference in total workload in anesthesia. The
      anesthesiologists indicated the same trend in their questionnaire responses.
      Evaluating only number of cases or total anesthetic time or medical treatment fee
      provides insufficient information to compare anesthesia workload. Our formula is
      a more appropriate index to quantify workload.

PMID- 15160676
TI  - [Regional differences in the number of anesthesiologists in Japan].
AB  - BACKGROUND: We have known the existence of regional differences in the number of
      medical doctors and the manpower shortage of anesthesiologists in Japan. METHODS:
      In the present investigation, we compared the number of regular members and Board
      Certified Anesthesiologists (BCA) of the Japan Society of Anesthesiologists (JSA)
      among prefectures and the Districts of JSA. RESULTS: Tokyo and Chugoku-Shikoku
      Districts of JSA had larger numbers of regular members of JSA per one hundred
      thousands population compared with Tokai, Kanto-Koshinetsu, and Tohoku Districts
      of JSA (the maximum difference among prefectures (MDAP) = 3.0 times and the
      maximum difference among the Districts (MDAD) = 2.4 times). Chugoku-Shikoku and
      Kyushu Districts of JSA had greater numbers of BCA per one hundred thousands
      population compared with Tokai, and Kanto-Koshinetsu Districts of JSA (MDAP = 3.1
      times and MDAD = 2.5 times). Hokkaido District of JSA had the largest percentages
      of both members of JSA and BCA to all medical doctors [(MDAP = 2.3 times and MDAD
      = 1.7times) and (MDAP = 2.6 times and MDAD = 2.0 times), respectively)]. Tokyo
      District of JSA had the largest numbers of both members of JSA and BCA per one
      thousand hospital beds [(MDAP = 3.4 times and MDAD = 2.5 times) and (MDAP = 3.2
      times and MDAD = 2.2 times), respectively)]. The regional differences in the
      number of regular members of JSA were bigger than those of the medical doctors
      (per one hundred thousands people (MDAP = 2.2 times and MDAD = 1.6 times) and per
      one thousand hospital beds (MDAP = 2.4 times and MDAD = 2.3 times),
      respectively]. CONCLUSIONS: There are remarkable regional differences in the
      number of regular members and BCA of JSA among prefectures and the Districts of
      JSA. We suspect that the regional differences in the number of anesthesiologists
      would affect the quality and system of corresponding clinical practice.

PMID- 15160677
TI  - [Comparison of emergency tracheal intubation performed on a table and on the
      ground].
AB  - BACKGROUND: Emergency tracheal intubation in the pre-hospital environment is
      generally more difficult than when performed at a hospital. Among the reasons
      making it more challenging, is the rescuer's position. We compared tracheal
      intubation between 2 settings, on a table and on the ground. METHODS: Ten staff
      anesthesiologists were asked to intubate mannequins placed on a table and on the
      ground. Measured variables included intubation time, Cormack grade, incidence of
      esophageal intubation, "crick" sound from the teeth of the mannequin, and degree
      of head tilt during intubation attempts. RESULTS: Mean intubation times on the
      table and ground were 12.6 +/- 3.9 and 14.7 +/- 6.5 seconds, respectively. No
      esophageal intubation occurred. Cormack grades and incidence of teeth click were
      significantly higher on the floor, whereas there was no difference regarding
      degree of head tilt between the 2 settings. CONCLUSIONS: Our results indicate
      that intubation on the ground is more difficult and may require a longer time to
      accomplish, even for experienced anesthesiologists. Therefore, those involved in
      airway management training for emergency personnel should acquire appropriate
      skills to teach tracheal intubation in such a difficult situation.

PMID- 15160678
TI  - [Incidence and characteristics of perioperative pulmonary thromboembolism in
      Japan].
AB  - BACKGROUND: Perioperative pulmonary thromboembolism (preoperative PTE) is widely
      recognized as one of the life-threatening perioperative complications in Japan.
      However, incidence of perioperative PTE is not well surveyed. The Japanese
      Society of Anesthesiologist (JSA) mailed the questionnaire about incidence of
      perioperative PTE and its characteristics to the institutions registered in JSA.
      METHODS: The questionnaire was mailed to 844 institutions. The items of the
      survey included age, sex, type of surgery and risk factors of the cases performed
      in 2002. Data were analyzed using chi-square test and Fisher's test, and P < 0.05
      was taken as significant. RESULTS: Four-hundred sixty-seven out of 844
      institutions responded (55.3%) effectively. There were 369 cases of perioperative
      PTE in 208 institutions (44.5% of the institutions responded). The incidence of
      perioperative PTE was 4.4 per ten thousand cases. Massive PTE or cardiac arrest
      at the onset occurred in 57 cases (15.4%). Out of these patients, 117 patients
      (31.7%) had obesity, and bed-ridden rest (> 4 days) patients and cancer patients
      were each 105 (28.5%). Sixty-six patients died from perioperative PTE, out of
      which 5 patients (7.5%) died during operation, 31 patients (47.0%) died within 7
      days after the operation, and 30 patients (45.5%) died 8 days after the
      operation. The commonest type of surgery among mortality cases was abdominal
      surgery (20 cases: 30.3%), and the commonest risk factor was being bedridden
      (34.5 cases: 51.5%). The patients who had developed PTE during surgery counted
      64, among whom the major type of operation was lower limb/pelvic surgery (36
      cases: 56.3%). Major risk factors were being bed-ridden in 25 cases (39.1%) and
      lower limb/pelvic fracture in 25 cases (39.1%). Despite having dangerous risk
      factors, 128 patients (57.7%) received the measures not recommended or did not
      receive any preventive measure for PTE. CONCLUSIONS: This survey revealed that
      the incidence of perioperative PTE in Japan is considerable. On the ground that
      most PTE could be prevented, it is suggested that by employing preventive
      measures for PTE, the incidence of perioperative PTE will decrease.

PMID- 15160679
TI  - [Juvenile rheumatoid arthritis. 1928].

PMID- 15160680
TI  - [Hip dislocation with fracture of the acetabulum. 1928].

PMID- 15160681
TI  - [Etiology of idiopathic scoliosis. 1928].

PMID- 15160682
TI  - [Fibrous ostitis of the minor trochanter--case study. 1928].

PMID- 15160683
TI  - [Chronic unreduced dislocations. 1928].

PMID- 15160684
TI  - [Arm amputation by the Krukenberg procedure. 1928].

PMID- 15160685
TI  - [Dislocation of the ankle joint. 1928].

PMID- 15160686
TI  - A randomized intervention to improve heart failure outcomes in community-based
      home health care.
AB  - This study examines the effects of a home health intervention designed to
      standardize nursing care, strengthen nurses' support for patient self-management
      and yield better CHF patient outcomes. Participants were 371 Medicare CHF
      patients served by 205 nurses randomized to intervention and control groups in a
      large urban home healthcare agency (HHA). The intervention consisted of an
      evidence-based nursing protocol, patient self-care guide, and training to improve
      nurses'teaching and support skills. Outcome measures included home care,physician
      and emergency department (ED) use, hospital admission, condition-specific quality
      of life (QoL), satisfaction with home care services and survival at 90 days. The
      intervention was associated with a marginally significant reduction in the volume
      of skilled nursing visits (p = .074), and a reduction variation in the typical
      number of visits provided (p < .05), without a significant increase in physician
      or ED use or patient mortality. Hypothesized improvement in other outcomes did
      not occur.

PMID- 15160687
TI  - Medical image. Dactylalgia.

PMID- 15160688
TI  - Need for a reliable system to measure body temperature.

PMID- 15160689
TI  - Editorial: Guidelines for Diagnosis and Treatment of Atherosclerotic
      Cardiovascular Diseases 2002.

PMID- 15160690
TI  - Contentious worker testing.

PMID- 15160691
TI  - Ozone surprise.

PMID- 15160692
TI  - HVAC officemate.

PMID- 15160693
TI  - Beyond the bench: go for the GLO.

PMID- 15160694
TI  - Forage findings: expanding the definition of EDCs.

PMID- 15160695
TI  - EMFs and DNA effects: potential mechanism elucidated.

PMID- 15160701
TI  - Cervical endplay assessment does not improve the efficacy of cervical
      manipulation.

PMID- 15160702
TI  - Acute low back pain improves rapidly, however recovery is not complete and
      recurrence is common.

PMID- 15160703
TI  - Abstracts of the British Geriatrics Society autumn meeting. 16-17 October 2003,
      London, United Kingdom.

PMID- 15160705
TI  - [Abstracts of the Neurology Meeting of the French Speaking Community. Strasbourg,
      France, 13-17 April 2004].

PMID- 15160704
TI  - [Position of the German Society for Prevention and Rehabilitation in Vascular
      Disease, DGPR on the study under the Health and Pension Insurance Scheme's
      Recommendation on Outpatient/Inpatient Rehabilitation: A. vom Orde et al.,
      "Outcomes of cardiac rehabilitation treatment and cost-effectiveness relations--A
      comparison between inpatient and outpatient rehabilitation programmes"].

PMID- 15160706
TI  - How much of general practice is based on evidence?

PMID- 15160707
TI  - "The cawing of the crow...Cassandra-like, prognosticating woe".

PMID- 15160708
TI  - [Abstracts of the XL Congress of the Brazilian Society of Tropical Medicine. 7-11
      March 2004, Aracaju, Sergipe, Brazil].

PMID- 15160709
TI  - Proceedings of the XVII National Congress of the Italian Society of
      Pathophysiology. Parma, Italy, 4-7 June 2003.

PMID- 15160710
TI  - Proceedings of the Sixth International Workshop on the Biology of Lactation in
      Farm Animals. July 2002. Quebec City, Canada.

PMID- 15160711
TI  - Current awareness on yeast.

PMID- 15160712
TI  - Proceedings of the Second International Conference on Thrombosis and Hemostasis
      Issues in Cancer. September 19-21, 2003. Bergamo, Italy.

PMID- 15160713
TI  - Eligibility determination for donors of human cells, tissues, and cellular and
      tissue-based products. Final rule.
AB  - The Food and Drug Administration (FDA) is requiring human cell, tissue, and
      cellular and tissue-based product (HCT/P) establishments to screen and test cell
      and tissue donors for risk factors for, and clinical evidence of, relevant
      communicable disease agents and diseases. The agency is amending the current good
      manufacturing practice (CGMP) and quality system (QS) regulations that apply to
      HCT/Ps regulated as drugs, medical devices, and/or biological products to clarify
      the role of the new donor-eligibility regulations in relation to existing CGMP
      regulations. By preventing the transmission of communicable disease by the wide
      spectrum of HCT/Ps that are marketed now or may be marketed in the future, the
      agency's action will improve protection of the public health and increase public
      confidence in new technologies.

PMID- 15160714
TI  - Proceedings of a Consensus Conference of the International Olympic Committee
      Medical Commission Nutrition and Sport Working Group. June 15-18, 2003. Lausanne,
      Switzerland.

PMID- 15160715
TI  - Slovakia has kept AIDS out despite money problems. But the country's eastern
      border will be put to the test as EU officials demand tighter controls.

PMID- 15160716
TI  - Emergency contraception kept as prescription only in USA.

PMID- 15160717
TI  - Chile agrees to emergency contraception for rape victims.

PMID- 15160718
TI  - France makes heatwave plans to protect elderly people.

PMID- 15160719
TI  - Pakistan recognises burden of non-communicable disease.

PMID- 15160721
TI  - HHS issues rules on financial conflicts.

PMID- 15160720
TI  - UNICEF taps religious leaders in vaccination push.

PMID- 15160722
TI  - Antiretrovirals give new hope and new life to South Africans. The long-awaited
      antiretroviral roll-out improves morale; at last there is hope for HIV/AIDS
      patients.

PMID- 15160723
TI  - [Scientific Conference: Silesian Days of Social Medicine and Public Health.
      Zabrze, Szczyrk 2002. Proceedings].

PMID- 15160724
TI  - Used hay.

PMID- 15160725
TI  - High cell density fed-batch cultivation of Escherichia coli using exponential
      feeding combined with pH-stat.
AB  - A new feeding strategy in fed-batch culture, exponential feeding combined with pH
      stat is suggested to avoid the accumulation of substrate in culture broth.
      Exponential feeding was stopped whenever a predetermined amount of limiting
      substrate was supplied and then pH change was observed. When pH rose above an
      upper limit due to the depletion of substrate, feeding was restarted. With this
      feeding strategy, recombinant Escherichia coli could be grown to 101 g/l by
      controlling the specific growth rate at 0.1 h(-1).

PMID- 15160726
TI  - Sarwar Jehan Zuberi.

PMID- 15160727
TI  - Emergency medical dispatch risks.

PMID- 15160728
TI  - Patient priorities.

PMID- 15160729
TI  - Detox reebox: stuff plumbers know about feet.

PMID- 15160730
TI  - Reference to preferences for cardiopulmonary resuscitation.

PMID- 15160731
TI  - Beyond primary blast injury.

PMID- 15160732
TI  - What has SARS taught us about infection control in nursing homes?

PMID- 15160734
TI  - Obituary. Wayne Streilein.

PMID- 15160733
TI  - Nurse practitioner/physician collaborative models of care.

PMID- 15160736
TI  - Impact of food industrial waste on anaerobic co-digestion of sewage sludge and
      pig manure.
AB  - The performance of an anaerobic digestion process is much dependent on the type
      and the composition of the material to be digested. The effects on the
      degradation process of co-digesting different types of waste were examined in two
      laboratory-scale studies. In the first investigation, sewage sludge was co
      digested with industrial waste from potato processing. The co-digestion resulted
      in a low buffered system and when the fraction of starch-rich waste was
      increased, the result was a more sensitive process, with process overload
      occurring at a lower organic loading rate (OLR). In the second investigation, pig
      manure, slaughterhouse waste, vegetable waste and various kinds of industrial
      waste were digested. This resulted in a highly buffered system as the manure
      contributed to high amounts of ammonia. However, it is important to note that
      ammonia might be toxic to the micro-organisms. Although the conversion of
      volatile fatty acids was incomplete the processes worked well with high gas
      yields, 0.8-1.0 m3 kg(-1) VS.

PMID- 15160735
TI  - Distribution of lead in relation to size of airborne particulate matter in
      Islamabad, Pakistan.
AB  - Airborne particulate matter (PM) collected from two sampling stations in
      Islamabad, Pakistan, was analyzed for lead content and size gradation. A high
      volume air sampler was used to trap particulates on glass fiber filters for 8-12
      h on a daily basis. Lead was estimated using a nitric acid digestion based AAS
      method on 44 samples from station 1 and 61 samples from station 2. Particle size
      fractions were categorized as <2.5, 2.5-10, 10-100 and >100 microm. The
      correlation between lead concentration and particle size was investigated. The
      results from two stations indicated average airborne lead concentrations of 0.505
      and 0.185 microg/m3. Enhanced levels of lead were measured at a maximum of 4.075
      microg/m3 at station 1 and 4.000 microg/m3 at station 2. PM < 2.5 and PM > 100
      were found to constitute the local atmosphere in comparable proportions. A
      comparison of the lead levels is made with the existing permissible levels of
      this element laid down by different international agencies.

PMID- 15160737
TI  - The localized environmental degradation of protected areas adjacent to bird
      feeding stations: a case study of the Australian brush-turkey Alectura lathami.
AB  - This study investigated the potential for wildlife feeding to artificially
      increase population densities of the Australian brush-turkey, Alectura lathami
      and assessed the indirect adverse effects that this may have on surrounding
      forest floor vegetation. Census counts and observations of feeding activity
      conducted in recreation areas of Australia's Gold Coast hinterland confirmed that
      brush-turkey population densities were significantly elevated by the provision of
      food by humans. Brush-turkey densities were high at sites where birds are
      actively fed, moderate at sites where birds feed opportunistically and low at
      sites where humans have negligible impact on local food availability. Brush
      turkeys caused significant environmental impact at sites where their population
      densities have been substantially elevated by active feeding. Across all sites,
      increases in brush-turkey density were accompanied by a significant decline in
      ground cover, leaf litter weight, seed density and seedling density. Natural
      environmental variables such as gradient, vegetation type and canopy cover did
      not explain the observed impacts. The impacts were consistent with those
      described in trampling studies and suggest that at high density, even small
      animals can have significant trampling impacts on their local environment. This
      study demonstrates that wildlife feeding can have detrimental impacts on the
      integrity of local environments and recommends greater consideration of small
      animals and their potential indirect impacts when regulating wildlife feeding in
      National Parks and other nature conservation areas.

PMID- 15160738
TI  - Mortality and morbidity benefits of air pollution (SO2 and PM10) absorption
      attributable to woodland in Britain.
AB  - Forests in Britain produce social and environmental benefits, in addition to
      marketable timber outputs. One such non-market benefit is the reduction in air
      pollution, linked to health impacts (mortality and morbidity). This study
      assesses the benefits of SO2 and PM10 absorption by trees in terms of extending
      life expectancy of the population and reducing hospital admissions. Working at a
      resolution of 1 km2 with woodland over 2 ha, it is estimated that, for Britain as
      a whole, woodland saves between 5 and 7 deaths, that would otherwise have been
      brought forward, and between 4 and 6 hospital admissions each year. The economic
      value of the health effect of woodland is estimated to be at least 900,000 pounds
      Sterling per year. Smaller areas of woodland, often located closer to population,
      sometimes strategically planted close to pollution sources, will generate
      additional air pollution absorption benefits to those estimated here. Researching
      such benefits would require more detailed data than is available at present for a
      national study. However, the health benefits of woodland are relatively small in
      comparison to other non-market forestry benefits.

PMID- 15160739
TI  - Modelling the costs of fox predation and preventive measures on sheep farms in
      Britain.
AB  - Economic analysis is a useful tool to aid decisions on what to do about wildlife
      impacts, such as those of vertebrate predators on livestock farmers. The case
      study of lamb predation by foxes in Britain is used to develop a theoretical
      economic model, with the aim of determining a financially optimal solution to
      minimise the total costs of livestock predation at the farm-level. Total costs
      include output losses and expenditure on preventive and control measures, in this
      case indoor housing and lethal fox control. The model is tested empirically with
      data from a questionnaire survey of sheep farmers and field data on fox
      population densities in Britain. Regression analyses are used to determine the
      relationships between lamb losses and expenditure on indoor housing, fox
      population density and other non-management characteristics. The effect of fox
      abundance on the cost of fox control is also assessed. Marginal analysis is used
      to determine the total cost-minimising solution from the farmer's point-of-view,
      in terms of how many ewes should be housed indoors and for how long, as well as
      how many foxes should be killed in addition to any lethal control already carried
      out. Optimal solutions vary according to farm characteristics, including flock
      size and the regional location of farms. In all cases, to minimise the costs of
      predation, as many ewes as possible should be housed. However, it is not
      worthwhile housing them for more than a day after lambing. Efficient fox
      predation management does not necessarily mean that lamb losses should be reduced
      to zero, and additional fox control is not worthwhile on the majority of farms.
      The analysis provides a framework for future evaluations of wildlife impacts and
      cost-effective management of these problems.

PMID- 15160740
TI  - Managing the adverse thermal effects of urban development in a densely populated
      Chinese city.
AB  - Guangzhou city in South China has experienced an accelerated urban development
      since the 1980s. This paper examines the impact of the urban development on urban
      heat islands through a historical analysis of urban-rural air temperature
      differences. Remote sensing techniques were applied to derive information on land
      use/cover and land surface temperatures and to assess the thermal response
      patterns of land cover types. The results revealed an overriding importance of
      urban land cover expansion in the changes in heat island intensity and surface
      temperature patterns. Urban development was also related to a continual air
      temperature increase in the 1980s and 1990s. The combined use of satellite
      derived vegetation and land cover distributions with land surface temperature
      maps provides a potential useful tool for many planning applications. The city's
      greening campaigns and landscaping designs should consider the different cooling
      effects of forest, shrubs and grassy lawns for temperature control and should
      plant more tall trees.

PMID- 15160742
TI  - Quantitative review of riparian buffer width guidelines from Canada and the
      United States.
AB  - This paper reviewed the provincial, territorial, and state guidelines for the
      retention of treed riparian buffers after timber harvest in Canada and the United
      States. Comparisons amongst jurisdictions were facilitated through the use of a
      standardized template for the classification of waterbodies. Mean buffer widths
      varied from 15.1 to 29.0 m for different waterbody types when both countries were
      combined. However, Canadian jurisdictions had wider buffers (except for
      intermittent streams). In part, this was due to the high percentage of Boreal
      jurisdictions in Canada and Southeast jurisdictions in the United States. The
      Boreal region had the widest buffers while Southeastern jurisdictions had the
      narrowest buffers. Just under half (approximately 44%) of the jurisdictions
      investigated had three or more modifying factors in the guidelines. Of these,
      waterbody type, shoreline slope, waterbody size, and presence of fish were the
      most common. Boreal and Pacific jurisdictions tended to have a more diverse set
      of waterbody size classes, waterbody types, and other modifying factors.
      Jurisdictions from the Midwest, Northeast, and Southeast maintained relatively
      simple 'one-size-fits-all' guidelines. Jurisdictions without modifying factors
      for slope or presence of fish applied wider baseline buffers than jurisdictions
      with these factors. A large percentage of jurisdictions (approximately 80%)
      allowed some selective harvest in buffers. However, these were often accompanied
      by relatively restrictive prescriptions. In comparison to the ecological
      recommendations, buffer widths for most jurisdictions were adequate to protect
      the aquatic biota and habitats but were, generally, less than recommended widths
      for terrestrial communities. In the future, two management trends are likely to
      continue, the shift towards more complicated guidelines and the expansion to
      larger-scale, watershed planning of riparian areas.

PMID- 15160741
TI  - Removal of phenol from aqueous solutions by adsorption.
AB  - Experiments have been conducted to examine the liquid-phase adsorption of phenol
      from water by silica gel, HiSiv 3000, activated alumina, activated carbon,
      Filtrasorb-400, and HiSiv 1000. Experiments were carried out for the analysis of
      adsorption equilibrium capacities and kinetics. The adsorption isotherm model of
      the Langmuir-Freundlich type was the best to describe adsorption equilibrium data
      for phenol for the adsorbents studied. Results of kinetic experiments indicated
      that HiSiv 1000 had the highest rate of adsorption among the adsorbents studied
      and therefore more detailed studies were carried out with this adsorbent. The
      influence of particle size, temperature, and thermal regeneration on adsorption
      of phenol by HiSiv 1000 was evaluated. From particle size experiments it appeared
      that adsorption capacity of HiSiv 1000 did not change by changing the particle
      size, but the rate of adsorption decreased considerably by increasing the
      particle size. The effect of temperature on adsorption was studied by determining
      equilibrium isotherms for HiSiv 1000 at 25, 40, and 55 degrees C. The results
      showed that adsorption capacity decreased with increasing temperature. Thermal
      regeneration of HiSiv 1000 was performed at 360 degrees C. It was observed that
      adsorption capacity of HiSiv 1000 did not change after 14 regeneration cycles.
      Equilibrium experiments showed that the adsorption capacities of activated carbon
      and Filtrasorb-400 were several times higher than that of HiSiv 1000.

PMID- 15160743
TI  - Application of value-focused thinking on the environmental selection of wall
      structures.
AB  - The decision of selecting building structures with respect to the environmental
      demand is an issue commonly addressed in environmental management. In this paper,
      the importance of considering the decision analysis technique value-focused
      thinking in the environmental selection of wall structures is investigated. In
      this context, a qualitative value model is developed in which the external and
      internal environmental factors are considered. The model is applied on a case
      study in which a decision should be made on three categories of exterior wall
      structures: wood, masonry and concrete. It is found that the wall structure made
      of wood is the most compatible option with respect to the external and internal
      environmental requirements of building structures.

PMID- 15160744
TI  - Multidetector CT and virtual endoscopy in the evaluation of the esophagus.
AB  - In this prospective study, we assessed the diagnostic capabilities of
      multidetector computed tomography (CT) in various esophageal pathologic
      conditions. Thirty-three patients underwent a multidetector CT study after
      esophageal distention by means of effervescent powder administered after
      induction of pharmacologic esophageal hypotonia. All acquired images were post
      processed with two- and three-dimensional software tools. The CT data were
      compared with the results of conventional radiology (33), endoscopy (28),
      endoscopy ultrasonography (14), or surgery (14). Follow-up ranged between 4 and
      15 months. Esophageal distention in the upper and middle thirds was classified as
      "good" in 32 of 33 cases (97%); in the lower third, esophageal distention was
      "good" in 21 of 33 cases (64%). Final diagnoses were leiomyoma (six cases),
      squamous cell carcinoma (six), adenocarcinoma (four), esophageal infiltration by
      thyroid cancer (two), benign polyposis (two), chronic esophagitis (five), post
      sclerotherapy stenosis (one), no abnormalities (seven). When good distention was
      achieved, the thickness of unaffected esophageal wall was less than 3 mm (range,
      1.5-2.4 mm; mean, 1.9 mm). Pathologic wall thickening was observed in 25 of 33
      cases (76%), with values ranging between 3.6 and 36 mm (mean, 9.6 mm). Spiral CT
      demonstrated 21 true positive cases, and seven true negative cases. There were
      four false negative cases and one false positive case. Sensitivity was 84%,
      specificity was 87%, diagnostic accuracy was 85%, positive predictive value was
      95%, and negative predictive value was 64%. Evaluation of the esophagus with
      multidetector CT is a promising technique and easy to use, allowing panoramic
      exploration, virtual endoluminal visualization, accurate longitudinal and axial
      evaluations, and simultaneous evaluation of T and N parameters.

PMID- 15160745
TI  - Inflammatory myofibroblastic tumor of the stomach with peritoneal dissemination
      in a young adult: imaging findings.
AB  - Inflammatory myofibroblastic tumors are lesions that most often affect young
      adults and children. These tumors have been found in numerous extrapulmonary
      sites but rarely in the stomach. It is unknown whether this process is reactive
      or neoplastic. They are infiltrative lesions and often extend through the gastric
      wall, sometimes reaching adjacent organs including the esophagus, duodenum,
      peritoneal cavity, spleen. pancreas, and liver. These features mimic malignancy
      on endoscopy and radiology. We report the ultrasound, color Doppler ultrasound,
      and helical computed tomographic findings of a gastric inflammatory
      myofibroblastic tumor with peritoneal dissemination in a young adult. To our
      knowledge, this is the first report of color Doppler ultrasound and helical
      computed tomographic findings of this rare disease entity.

PMID- 15160746
TI  - Duodenal angiodysplasia: MR angiographic evaluation.
AB  - We describe a patient in whom endoscopy failed to determine the origin of
      gastrointestinal bleeding, and magnetic resonance angiography showed dilated
      inferior pancreaticoduodenal veins that were considered indirect signs of the
      duodenal angiodysplasia. Incidentally, a connection between the inferior vena
      cava and the inferior pancreaticoduodenal veins were also noted. Repeat endoscopy
      and catheter angiography confirmed the presence of the angiodysplasias.

PMID- 15160747
TI  - CT findings of increased splanchnic circulation in a case of celiac sprue.
AB  - We report a diagnosis of celiac disease first suggested by the computed
      tomographic appearance, which included findings indicative of increased
      splanchnic circulation. Similar findings have been reported with angiography and
      ultrasound but, to our knowledge, have not been reported with computed
      tomography.

PMID- 15160748
TI  - CT of small bowel ischemia.
AB  - We evaluated the computed tomographic (CT) features of small bowel (SB) ischemia
      and necrosis and correlated the findings with clinical outcome or patient
      prognosis. Sixty-eight surgically or angiographically proved cases of SB ischemia
      were retrospectively reviewed. The CT features of intestinal ischemia were
      divided into three groups: (A) thinned bowel wall with poor enhancement,
      intramural gas, or portal venous gas; (B) thickened SB wall without superior
      mesenteric vein thrombosis; and (C) thickened SB wall with superior mesenteric
      vein thrombosis or intussusception. The evaluated factors included bowel wall or
      mucosal enhancement pattern, SB dilatation, mesenteric edema, and CT evidence of
      narrowing or occlusion of the superior mesenteric artery or vein. The bowel
      necrosis rates and mortalities were compared with chi-square test. Oral contrast
      material was not administered. Intramural gas and SB dilatation were associated
      with a higher bowel necrosis rate (eight of eight, 100%, and 17 of 21, 81%,
      respectively) in group A. Poor mucosal enhancement of the thickened bowel wall
      indicated a higher bowel necrosis rate in groups B (six of seven, 86%) and C (12
      of 12, 100%) than did normal mucosal enhancement. Only intramural gas was
      accompanied with a higher mortality (six of eight, 75%). Intramural gas of a
      thinned bowel wall and poor mucosal enhancement of a thickened small bowel wall
      are useful signs of bowel necrosis. Intramural gas would indicate poor patient
      prognosis.

PMID- 15160750
TI  - Ileocecal actinomycosis: a case report.
AB  - A 51-year-old male with a clinical history of abdominal pain and bloody diarrhea
      underwent spiral computed tomography of the abdomen with intravenous contrast
      medium enhancement. The findings were an inflammatory mass with cystic and solid
      characteristics arising from the ileocecal region and extending to the peritoneum
      and right iliopsoas muscle, with adjacent lymphadenopathy. Histology after
      surgical resection confirmed the diagnosis of actinomycosis lesions in
      perienteric fat.

PMID- 15160749
TI  - Small bowel Crohn disease: sonographic features.

PMID- 15160751
TI  - Intussusception due to intestinal anisakiasis: a case report.
AB  - This report describes our experience of intussusception due to intestinal
      anisakiasis which was treated by laparoscopy-assisted surgery. The unique
      sonographic findings of this complication were a pseudokidney sign and a target
      sign with an edema of Kerckring's folds in the intussusceptum. Surgeons should
      know about intussusception as a rare complication of intestinal anisakiasis.
      Sonography, computed tomography and laparoscopy are helpful in diagnosing and
      treating this complication.

PMID- 15160752
TI  - Adult colocolic intussusception: demonstration by conventional MR techniques.
AB  - Intussusception is a rare condition in adults. We report a case of a 69-year-old
      woman referred to our institution for lower left quadrant abdominal pain, weight
      loss, and occasional episodes of constipation and rectal hemorrhage. The patient
      underwent plain radiography, ultrasonography, and magnetic resonance imaging of
      the pelvis. The final diagnosis was colocolic intussusception due to a neoplastic
      lead point.

PMID- 15160753
TI  - Doppler ultrasound for TIPS: does it work?
AB  - The role of transjugular intrahepatic portosystemic shunt (TIPS) in the
      management of complications of portal hypertension such as variceal hemorrhage
      and ascites is well established. However, TIPS has a limited patency due to
      dysfunction consisting in occlusion or stenosis of the intrahepatic tract or
      stenosis of the outflow hepatic vein. Timing of dysfunction cannot be predicted,
      so routine surveillance and percutaneous intervention are continuously required
      to maintain TIPS patency. Trans-shunt venography is the gold standard technique
      in TIPS evaluation, but it is expensive and invasive. Doppler ultrasound (DU) has
      been the most commonly used noninvasive tool in TIPS patency. Despite many
      reported series, its role remains controversial. After more than 10 years of
      experience with TIPS, we followed our patients with DU and trans-shunt venography
      to establish Doppler criteria of dysfunction and its accuracy in assessing shunt
      dysfunction.

PMID- 15160754
TI  - Stent-grafts in TIPS.

PMID- 15160755
TI  - Specificity of SPIO particles for characterization of liver hemangiomas using
      MRI.
AB  - We investigated the specificity of superparamagnetic iron oxide (SPIO)-enhanced
      T1-weighted spin-echo (SE) magnetic resonance (MR) images for the
      characterization of liver hemangiomas. When imaging liver hemangiomas, which are
      the most frequent benign liver tumors, a method with very high specificity is
      required, which will obviate other studies, follow-up, or invasive diagnostic
      procedures such as percutaneous biopsy. Eighty-three lesions were examined by MR
      imaging at 1.5 T before and after intravenous injection of SPIO particles.
      Lesions were categorized as follows according to the final diagnosis: 37
      hemangiomas, nine focal nodular hyperplasias (FNHs), 19 hepatocellular carcinomas
      (HCCs), and 18 metastases. Their signal intensity values were normalized to
      muscle and compared. The only lesions showing a significant increase in signal
      intensity ratio (lesion to muscle) on postcontrast T1-weighted SE images were
      hemangiomas (p < 0.001). The signal intensity ratio of hemangiomas increased on
      average by 70%. Based on receiver operating characteristic analysis and using a
      cutoff level of 50% signal increase, the specificity and sensitivity of SPIO
      enhanced MR imaging for the characterization of hemangiomas would be 100% and
      70%, respectively. The T1 effect of SPIO particles can help differentiate
      hemangiomas from other focal liver lesions such as FNHs, HCCs, and metastases and
      may obviate biopsy. When using SPIO particles for liver imaging, it is useful to
      add a T1-weighted sequence to T2-weighted images, thereby providing additional
      information for lesion characterization.

PMID- 15160756
TI  - Contrast enhanced MR-guided biopsy of hepatocellular carcinoma.
AB  - Magnetic resonance (MR)-guided liver biopsy was performed in three patients with
      hepatocellular carcinoma. The tumor was considered (n = 2) or proven (n = 1)
      inaccessible with ultrasound or computed tomographic guidance. Because all
      lesions were poorly delineated on nonenhanced MR imaging, contrast agents (Gd
      BOPTA, n = 1; ferucarbotran, n = 2) were applied to facilitate biopsy in an open
      low-field scanner. Postcontrast tumor conspicuity was fair in the patient
      receiving Gd-BOPTA and excellent in both patients receiving ferucarbotran, and
      biopsy was successful in all cases.

PMID- 15160757
TI  - Primary neuroendocrine tumors of the liver: MRI features in two cases.
AB  - We report on two patients who underwent magnetic resonance imaging (MRI) as part
      of the evaluation of focal liver lesions. Both lesions had completely different
      MRI appearances, showing characteristics of benign and malignant liver lesions.
      Neither patient had clinical signs of endocrine hyperactivity, and both underwent
      subsequent liver resection. Histology showed neuroendocrine liver tumors in both
      patients; and because no primary tumor could be identified after careful search,
      the diagnosis of primary neureoendocrine tumor of the liver was established. Our
      observations suggest that primary neuroendocrine tumors of the liver may have a
      wide spectrum of appearances on MRI.

PMID- 15160758
TI  - Visceral leishmaniasis with multiple nodular lesions of the liver and spleen: CT
      and sonographic findings.
AB  - Visceral leishmaniasis is a severe disease caused by the intracellular protozoa
      Leishmania donovani. Diagnosis is based on examination of bone marrow or
      serology. The role of imaging techniques as diagnostic tools remains to be
      established in visceral leishmaniasis. We report multiple nodular lesions in the
      liver and spleen on ultrasonography and computed tomography in a patient with
      visceral leishmaniasis. To our knowledge, this is the first reported case of
      multiple nodular hepatosplenic lesions in visceral leishmaniasis.

PMID- 15160759
TI  - Neurilemmoma of the diaphragm mimicking a liver tumor: case report.
AB  - A 47-year-old male with a solid, previously cystic tumor in the subphrenic part
      of the liver consulted for surgery. Laparotomy showed a well-circumscribed tumor
      originating from the diaphragm, which made a significant depression in the liver.
      Complete removal of the tumor was achieved. Pathologic examination led to a
      diagnosis of neurilemmoma originating from the diaphragm.

PMID- 15160760
TI  - Usual and unusual causes of extrahepatic cholestasis: assessment with magnetic
      resonance cholangiography and fast MRI.
AB  - Cholestasis may result from hepatocellular (intrahepatic) disease or biliary
      tract (extrahepatic) abnormalities. Etiologies causing extrahepatic cholestasis
      are extremely diverse and invasive procedures, such as endoscopic retrograde
      cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography
      (PTC), were previously required to establish the diagnosis. Due to refinements of
      magnetic resonance imaging (MRI) techniques, the patient with extrahepatic
      cholestasis currently can be evaluated noninvasively, and the information
      revealed frequently exceeds the findings obtained by ERCP and PTC. In this essay,
      we illustrate the classic MR cholangiographic (MRC) and MRI features of a variety
      of disorders causing extrahepatic cholestasis, including non-neoplastic disorders
      of the biliary tract (congenital abnormalities, infectious processes, iatrogenic
      disorders, and postsurgical complications) and neoplastic conditions (e.g.,
      tumors of the pancreas, biliary tree, liver, ampulla, and regional lymph nodes).
      In most cases, familiarity with the key MRC features in addition to information
      obtained via cross-sectional MR images provide sufficient information for
      adequate lesion characterization.

PMID- 15160761
TI  - Large cholesterol polyp of the gallbladder mimicking gallbladder carcinoma.
AB  - Gallbladder tumors larger than 10 mm in diameter have a high incidence of
      malignancy. We report an extremely rare case of a large cholesterol polyp of the
      gallbladder mimicking gallbladder carcinoma. Ultrasonography and computed
      tomography showed a larger papillary mass in the fundus of the gallbladder with a
      maximum diameter of about 30 mm, the largest gallbladder polyp ever reported to
      our knowledge.

PMID- 15160762
TI  - Gallbladder carcinoma and chronic cholecystitis: differentiation with two-phase
      spiral CT.
AB  - The objective of the present study was to determine whether an analysis of two
      phase spiral computed tomographic (CT) features provides a sound basis for the
      differential diagnosis between gallbladder carcinoma and chronic cholecystitis.
      Eighty-two patients, 35 with gallbladder carcinoma and 47 with chronic
      cholecystitis, underwent two-phase spiral CT. We reviewed the two-phase spiral CT
      features of thickness and enhancement pattern of the gallbladder wall seen during
      the arterial and venous phases. Mean wall thicknesses were 12.6 mm in the
      gallbladder carcinoma group and 6.9 mm in the chronic cholecystitis group. The
      common enhancement patterns seen in gallbladder carcinoma were (a) a highly
      enhanced thick inner wall layer during the arterial phase that showed
      isoattenuation with the adjacent hepatic parenchyma during the venous phase (16
      of 35, 45.7%) and (b) a highly enhanced thick inner wall layer during both phases
      (eight of 35, 22.9%). The most common enhancement pattern of chronic
      cholecystitis was isoattenuation of the thin inner wall layer during both phases
      (42 of 47, 89.4%). In conclusion, awareness of the wall thickening and
      enhancement patterns in gallbladder carcinoma and chronic cholecystitis on two
      phase spiral CT appears to be valuable in differentiating these two different
      disease entities.

PMID- 15160763
TI  - Asymptomatic nonspecific serum hyperamylasemia and hyperlipasemia: spectrum of
      MRCP findings and clinical implications.
AB  - We assessed the magnetic resonance cholangiopancreatographic (MRCP) findings in
      patients with asymptomatic, mild elevations of serum amylase and lipase levels to
      determine whether there might be a pathoanatomic cause for these laboratory
      abnormalities. MRCP was performed in 633 consecutive patients. Of these, 54
      (8.5%) images were obtained in patients with asymptomatic serum hyperamylasemia
      and hyperlipasemia. MRCP was performed on a 1.0-T MR system; breath-hold gradient
      recall, half-Fourier acquisition, and rapid acquisition with relaxation
      enhancement sequences were obtained. Findings were verified by follow-up, biopsy,
      or surgery. One-sided, large-sample z tests were used to compare the incidence of
      abnormalities between the study and control groups (579 patients). The pancreas
      appeared abnormal on MRCP in 31 patients (57%), including the pancreas divisum in
      10 patients (18.5%). Other findings included morphologic changes compatible with
      chronic pancreatitis in nine patients (16.6%) and a healed pancreatic laceration,
      juxtapapillary duodenal diverticulum, papillary sclerosis, intraductal pancreatic
      lithiasis, and hemochromatosis in one patient each (1.9%). Small cystic lesions
      (< 1 cm) within the pancreas were seen in 15 patients (27.8%). In eight patients,
      these were associated with other abnormalities (pancreas divisum in three
      patients, chronic pancreatitis in four, and pancreatic laceration in one). No
      malignancy was diagnosed. The incidences of normal examination (p = 0.01),
      pancreas divisum (p < 0.005), and a small cystic lesion (p = 0.01) as solitary
      findings in this subgroup of patients were significantly higher when compared
      with the remainder of the studied population. Investigation of asymptomatic
      patients with nonspecific hyperamylasemia and hyperlipasemia by means of MRCP
      yielded pancreatic findings in more than 50% of these patients. Pancreas divisum
      was found more often than expected in the general population.

PMID- 15160764
TI  - Percutaneous biopsy of periarterial soft tissue cuffs in the diagnosis of
      pancreatic carcinoma.
AB  - Pancreatic cancer may present on computed tomography (CT) as an isolated cuff of
      tumor surrounding the superior mesenteric artery (SMA) or celiac trunk, without
      an identifiable pancreatic mass. We reviewed our experience with imaging-guided
      biopsy of the soft tissue cuff in this patient group. A retrospective review of
      our interventional database identified 163 patients referred for biopsy of
      suspected pancreatic carcinoma. Of these, eight patients underwent biopsy of an
      isolated cuff of soft tissue encasing the SMA (n = 6) or celiac trunk (n = 2).
      None of these eight patients had an identifiable pancreatic mass. The mean width
      of tissue cuff biopsied was 1.3 cm (range, 0.9-2.0 cm). Nine imaging-guided
      biopsies were performed in eight patients. Five biopsies were performed with
      color Doppler ultrasound and four with CT fluoroscopy. There was a median of two
      needle passes per procedure (range, 1-4). In six cases, a diagnosis of pancreatic
      adenocarcinoma was made at the first biopsy session. In one patient, ultrasound
      guided biopsy was negative, but subsequent CT-guided biopsy was positive. In one
      additional patient with chronic pancreatitis, biopsy revealed benign fibrous
      tissue. There were no procedure-related complications. In patients with suspected
      pancreatic cancer (but without a focal parenchymal mass), imaging-guided biopsy
      of isolated periarterial tissue cuffs of tumor is accurate and safe.

PMID- 15160766
TI  - Diagnosis of adnexal torsion in the third trimester of pregnancy: a case report.
AB  - The diagnosis of adnexal torsion is difficult to establish on the basis of
      symptoms, physical findings, or radiologic techniques. If possible, in pregnancy
      the diagnostic workup should avoid any risk of drug administration, and the
      indication for a surgical intervention needs to be severe. Between 10% and 20% of
      ovarian torsions are associated with pregnancy, but adnexal torsion in the third
      trimester is rare. We present the case of a 22-year-old female presenting with a
      sudden onset of severe right lower quadrant abdominal pain associated with nausea
      and vomiting. The presumptive diagnosis was appendicitis. Transvaginal sonography
      showed some free fluid in the pouch of Douglas, but could not define the accurate
      diagnosis. In transabdominal ultrasound, a predominantly hyperechogenic mass
      containing small cysts was found in the right lower abdomen. No blood flow within
      the mass was detected with color and power Doppler sonography. With ultrasound,
      the anatomic relation of the mass could not be precisely identified. Magnetic
      resonance imaging clearly delineated the mass, which was due to enlargement of
      the right ovary, with predominately hyperintense signal containing small areas
      with hypointense lesions in T2-weighted images, a potential sign of hemorrhagic
      infarction. The mesovarium was hyperintense in T2-weighted images and also
      enlarged. The left ovary seemed to be normal. Due to the displacement of the
      ovaries in the second and third trimesters, the diagnostic workup is very largely
      restricted when using transvaginal ultrasound. Especially in pregnancy, it is
      mandatory to obtain a reliable diagnosis to reduce any risk to the fetus. Our
      case report indicates that the combination of magnetic resonance imaging and
      Doppler sonography fulfills these requirements and allows for accurate and fast
      diagnosis of adnexal torsion.

PMID- 15160765
TI  - Delivery related rupture of the gravid uterus: imaging findings.
AB  - Rupture of the gravid uterus is a rare, life-threatening obstetric complication.
      Major symptoms are hypovolemic shock and abdominal pain during late pregnancy or
      after vaginal delivery. Immediate surgical therapy is required. We report a case
      of uterine rupture after vaginal delivery diagnosed by means of ultrasonography
      and computed tomography.

PMID- 15160767
TI  - Uterine fibroids: targeted embolization, an update on technique.
AB  - Uterine fibroid embolization has become an attractive alternative therapy for
      symptomatic uterine fibroids. Since its introduction, the applied embolization
      technique has undergone several refinements. Complete fibroid devascularization
      to block uterine arteries was the initial goal. Thereafter, more sophisticated
      techniques for targeted embolization of the fibroid to preserve cervical and
      vaginal branches and ovarian anastomosis were being performed by more and more
      interventionists. In addition, the use of calibrated embolic agents has become
      more and more popular. In this article we provide an update on the modern uterine
      fibroid, targeted embolization technique, including a summary of catheterization
      related problems, flaws, and tricks.

PMID- 15160769
TI  - Antineoplastics declared occupational hazard.

PMID- 15160770
TI  - Pharmacist input increases with new JCAHO surveys.

PMID- 15160768
TI  - Transrectal ultrasound-guided biopsy of the prostate gland: value of 12 versus 6
      cores.
AB  - We investigated the effect on prostate carcinoma detection of 12 versus 6 core
      biopsies at transrectal ultrasound (TRUS), when all biopsies are taken from the
      lateral peripheral zone. This was a prospective study of 202 consecutive men,
      ages 51 to 81 years, referred for TRUS-guided biopsy of the prostate gland. All
      patients had prostate serum antigen levels higher than 4.0 ng/mL and/or abnormal
      digital rectal examination. In each case three biopsies were taken from the
      peripheral zones of the right and left lobes of the prostate. Biopsies were taken
      at the apex, midway between the apex and the base, and at the base. A second set
      of biopsies was taken from the same regions and analyzed separately. In total,
      twelve biopsies were taken. Note was subsequently made of additional carcinoma
      diagnosis increase in Gleason grade, and new diagnoses of carcinoma in the
      opposite side of the gland diagnosed on the second set of biopsies alone. Seventy
      eight of the 202 men (38.6%) had prostatic carcinoma diagnosed on TRUS-guided
      biopsy. Of these 78 patients, six were diagnosed with malignancy based on the
      second set of biopsies alone, a 2.9% increase in the 202 patients, representing
      an increased yield of 8.3% (95% confidence interval, 5.3-28.6%). In nine cases
      (12.5%; 95% confidence interval, 6.2-22.9%), the Gleason tumor grade was
      increased on the second set of sextant biopsies; in an additional nine cases,
      carcinoma was detected in the opposite side of the gland. There were two
      complications (1%). A 12- versus six-core biopsy strategy for TRUS-guided biopsy
      of the prostate gland improves detection and histologic grading of prostate
      carcinoma. The added benefit of additional biopsies was lower in this series than
      in some prior studies using extensive biopsy protocols.

PMID- 15160771
TI  - JCAHO gears up to survey sterile compounding practices.

PMID- 15160773
TI  - Recent changes to FDA-approved labeling.

PMID- 15160772
TI  - Low health literacy is high among Americans, studies say.

PMID- 15160774
TI  - A first step... toward full Medicare recognition of pharmacists as providers.

PMID- 15160775
TI  - Selected medication-error data from USP's MEDMARX program for 2002.
AB  - PURPOSE: Records from USP's MEDMARX database of medication errors for 2002 were
      studied. METHODS: Records of medication errors submitted to MEDMARX by
      participating health care institutions during 2002 were analyzed for error
      category index (whether a medication error actually occurred, whether it reached
      the patient, and, if so, the effect), node (the point in the medication-use
      process where the error occurred), type of error, cause, contributing factors,
      and drug products involved. RESULTS: The number of participating institutions was
      482, and the number of medication error records released to MEDMARX was 192,477,
      an 82.2% increase from 2001. Errors that did not reach the patient were seen in
      35% of the records, errors that reached the patient were seen in 49%, and errors
      that may have contributed to or resulted in harm were seen in 2%. The nodes,
      types of errors, causes of errors, contributing factors, and leading products by
      generic name are discussed. CONCLUSION: An analysis of over 192,000 records of
      medication errors submitted by nearly 500 health care facilities to USP's MEDMARX
      database in 2002 produced detailed information on the scope and nature of
      medication errors.

PMID- 15160776
TI  - Predictors of satisfaction of health plan members with prescription drug
      benefits.
AB  - PURPOSE: Relationships between sociodemographic and health plan characteristics
      and health plan member satisfaction with prescription drug benefits were studied.
      METHODS: A survey was mailed in November 2002 to a stratified random sample of
      14,141 people covered by a pharmacy benefit management company (PBM) who had made
      at least one prescription drug claim during the second quarter of 2002. Survey
      recipients had commercial health insurance and were 19-64 years of age.
      Participants were stratified by drug benefit plan design (two-tier copayment
      system, three-tier copayment system, coinsurance, or closed formulary). The
      survey contained 39 questions covering satisfaction with the prescription drug
      benefit, health-related attitudes and knowledge, and experience with the benefit.
      Predictors of satisfaction were examined by using logistic regression with
      probability weights. RESULTS: A total of 3819 surveys were returned (response
      rate, 27%). Respondents were more likely to be mail-order pharmacy users and less
      likely to be enrolled in a plan with a closed formulary. Out-of-pocket costs were
      viewed as the most important feature of the pharmacy benefit. In the logistic
      regression, higher copayments, coinsurance, closed formularies, intensive managed
      care, large health care premiums, a recent increase in copayments, and a recent
      denial of coverage were associated with lower satisfaction with the prescription
      drug benefit. Excellent health and use of mail-order pharmacy were associated
      with greater satisfaction. CONCLUSION: The extent to which health plan members
      served by a PBM had to share drug costs was the strongest determinant of
      satisfaction with the prescription drug benefit.

PMID- 15160777
TI  - Evaluation of drug information databases for personal digital assistants.
AB  - PURPOSE: Core and supplemental drug information databases available for use with
      personal digital assistants (PDAs) were evaluated. METHODS: Ten core (or
      standalone) databases, six drug interaction analyzers, and three dietary
      supplement databases used with the Palm and Pocket PC operating systems were
      selected for study. The databases were rated for scope (the absence or presence
      of an answer to a drug information question), completeness (the comprehensiveness
      of an answer), and ease of use (the number of hypertext links needed to reach the
      desired answer). A total of 14 weighted categories, consisting of 146 and 30 drug
      questions for the core and supplemental databases, respectively, were used to
      determine the overall scores. RESULTS: The best overall performers were, in order
      of total scores, Lexi-Drugs Platinum, Tarascon Pocket Pharmacopoeia, ePocrates Rx
      Pro, and Clinical Pharmacology OnHand. The databases with the lowest composite
      scores were Triple i Prescribing Guide and A2Z Drugs. CONCLUSION: Drug
      information databases for PDAs varied in scope, completeness, and ease of use.
      The results may help clinicians find the most appropriate product for their
      practice setting.

PMID- 15160778
TI  - Conforming to HIPAA regulations and compilation of research data.
AB  - PURPOSE: A set of deidentified patient data compliant with the Health Information
      Portability and Accountability Act (HIPAA) was compiled, the data lost as a
      function of unique data elements (UDEs) were measured, and the deidentified data
      were tested for potential for reidentification. METHODS: After approval by the
      institutional review board of an integrated health system, a limited-data set was
      created by querying the health system's pharmacy, administrative, and financial
      files for patients discharged between January 1 and December 31, 2000. Using the
      HIPAA "safe-harbor" method, this limited-data set was converted into a
      deidentified-data table for future statistical analysis, and UDEs in both data
      sets were identified and quantified. Unique combinations of commonly available
      data were also identified. RESULTS: The limited-data set, representing 4,738
      patient discharges, contained 810,456 UDEs in 322,657 records organized into four
      data tables (demographics, diagnoses, medication orders, and laboratory test
      results). The deidentified-data table, representing 4,722 discharges, contained
      562,171 UDEs in 128 data-type columns in a single data table. About 31% of the
      data volume was lost. Much of the information lost was of the type that is of
      special interest to researchers (e.g., time between episodes of care, ages of >89
      years). CONCLUSION: A study suggested that deidentified patient data with a
      reasonable degree of protection against reidentification were less complete than
      may be necessary for good research.

PMID- 15160779
TI  - Dyslipidemia treatment among patients with coronary artery disease in a managed
      care organization.
AB  - PURPOSE: The statin-prescribing patterns in a large managed care organization and
      the effectiveness of statin prescriptions in lowering low-density-lipoprotein
      (LDL) cholesterol levels in patients with coronary artery disease (CAD) or risk
      equivalent patients were examined. METHODS: A retrospective review of the records
      in an integrated medical, pharmacy, and laboratory database was performed. The
      qualifying period for the study began January 1, 1999, and ended December 31,
      2000; the reporting period extended from January 1, 2001, to December 31, 2001.
      Patients included in this study had a medical claim indicative of a diagnosis of
      CAD or risk equivalence during the qualifying 18-month period. The data were
      examined to determine percentages of patients who were tested for circulating LDL
      cholesterol levels, were prescribed statins, and achieved the LDL cholesterol
      goal recommended by the National Cholesterol Expert Panel. Physician prescribing
      patterns were also examined. RESULTS: During the 12-month analysis period of the
      study, 24% of patients were tested for circulating LDL cholesterol levels, and
      39.8% received at least one statin. Of patients whose LDL cholesterol values were
      documented and who received statins, 44.5% achieved goal LDL cholesterol levels.
      Of patients who were tested and did not receive statins, 29.8% achieved the LDL
      cholesterol goal. Cardiologists prescribed statins to CAD patients at a higher
      rate than other specialists or primary care providers. CONCLUSION: Patients with
      a diagnosis of CAD or risk equivalence, who would benefit from treatment to
      reduce circulating LDL cholesterol levels, were significantly undertreated.

PMID- 15160780
TI  - Stability of lorazepam in 0.9% sodium chloride stored in polyolefin bags.

PMID- 15160781
TI  - The Medicare Prescription Drug, Improvement, and Modernization Act of 2003:
      implications for health-system pharmacy.

PMID- 15160782
TI  - 2003 ASHP Leadership Conference on Pharmacy Practice Management executive summary
      -looking to the future: leading and managing change.

PMID- 15160783
TI  - Role of the placebo effect in evaluating antidepressant efficacy.

PMID- 15160784
TI  - A publicly managed Medicaid substance abuse carve-out: effects on spending and
      utilization.
AB  - In 1998, Michigan Medicaid "carved out" substance abuse treatment from its
      medical plans, transferring the management responsibility and substantial
      financial risk to 15 specialized local entities called coordinating agencies. All
      these agencies were either non-profit or publicly owned, unlike carve-out
      entities in many other states. By the second year of the risk-based carve-out
      (2000), Medicaid payments per eligible were 9.1% lower than in the last year
      before the carve-out (1998). Reductions were largely achieved by serving fewer
      clients, not by reducing payments per client. Agencies faced with revenue
      reductions or small increases were more likely to reduce treatment spending.

PMID- 15160785
TI  - Performance-based contracting: turning vocational policy into jobs.
AB  - The New York State Office of Mental Health has implemented a 2-year demonstration
      to determine if performance-based contracting (PBC) improves rates of competitive
      employment for people with serious persistent mental health conditions, and
      promotes best practice among providers. This article reports the interim findings
      from the demonstration. Initial results suggest that PBC is reaching the target
      population and promoting employment for a significant proportion of participants.
      It is also stimulating agency re-evaluation of consumer recruitment strategies,
      job development models, staffing patterns, coordination with support services,
      methods of post-placement support, and commitment to competitive employment for
      consumers.

PMID- 15160786
TI  - Race, schizophrenia, and admission to state psychiatric hospitals.
AB  - The relationships among race, diagnoses of schizophrenia, mood disorder, and
      admission to state psychiatric hospitals were examined in this study. Two
      hypotheses and two research questions represented these relationships. Data were
      analyzed from a sample of 2,311 individuals who had hospital admissions in
      Indiana during an 8-year period. In comparison with the general population,
      African Americans were found to be overrepresented among inpatients with
      diagnoses of schizophrenia. African Americans were four times more likely than
      White inpatients to receive a diagnosis of schizophrenia. Accountability tools to
      address issues of differential hospitalization rates and overdiagnosis of
      schizophrenia are discussed.

PMID- 15160787
TI  - Reducing disparity in behavioral health services: a report from the American
      College of Mental Health Administration.
AB  - The 2003 AMCHA Summit was an initial step. It served to provide a broad outline
      of the socio-political context and key issues involved in reducing disparities,
      and it provided some momentum for change. However, much more work remains to be
      done. The summit clearly demonstrated that the reduction of disparities requires
      a multi-level approach and multi-disciplinary leaders. As a neutral convener,
      AMCHA is in a unique position to help advance the debate and lead the field. The
      membership includes researchers, administrators, clinicians, and policy makers
      from all levels of the behavioral health system. As noted, a change agenda needs
      to include efforts at national, state, and local levels involving consumers,
      providers, purchasers, oversight organizations, and researchers. ACMHA is
      committed to advancing the field and helping the national effort to reduce
      disparities. Examples of potential projects include the following: Training: Much
      has been done to develop effective cultural-competency training modules and to
      guide states in its implementation. No one should reinvent the wheel at this
      time. Funding should be targeted to provide incentives to states for
      dissemination of existing training curricula and the documentation of
      effectiveness to all providers and administrators. DATA: Nationally, the field
      will benefit from data standards for the collection of and reporting on system
      disparities. This will facilitate interstate comparisons and provide baseline
      data for change efforts. Conducting surveys of providers, health plans, and
      public behavioral health systems on the availability and current uses of data by
      race and ethnicity is one example of a useful first step in this process of
      setting data standards. RESEARCH: Further research on the nature and causes of
      disparity is needed. There should be systematic research on factors influencing
      access, treatment, and outcomes for people of different cultures. Initially,
      because of the difficulties in deciding on standardized outcome measures, the
      encounter and claims data will provide the most useful information for analysis.
      Later, as standardized outcome measures are more widely utilized and the data
      collected, it may be possible to look for racial and ethnic differences in
      outcomes. The research agenda needs to be developed with a focus on services and
      health systems research data. Demonstrations: Demonstration efforts are urgently
      needed, similar to Connecticut's initiative, that integrate data on disparities
      with provider reporting, performance contracting, and system-wide interventions.
      These best practices need to be shared with the field. Coordination: The Summit
      showed that many are eager to learn from others in this area. As we move from
      further research to demonstration initiatives, AMCHA can play a role in
      coordinating these projects, particularly at the state and perhaps local levels.
      State efforts can benefit from best-practice presentations from other states and
      by an improved understanding of the nature and scope of the change required at a
      programmatic and local level. Local efforts need to clearly incorporate the views
      and perspectives of members of the community and consumers. The 2003 ACMHA Summit
      provided a foundation and a framework for work to proceed at all levels of the
      behavioral health delivery system. To accomplish meaningful change, we challenge
      SAMHSA, and the other federal agencies to provide the leadership to (1) develop
      common and core-performance measures focused on the reduction of disparities, (2)
      coordinate the research agenda, and (3) facilitate the use of new information
      technologies to collect and review these data. This is completely consistent with
      the vision of federal "leadership by example" that has been outlined by the
      Institute of Medicine (2003b) for the implementation of the "Crossing the Quality
      Chasm" report. We need to facilitate the efforts of the states and the federal
      government to identify and reduce disparities and provide a forum for states to
      share the results of their efforts, to benchmark their performance, and seek
      technical assistance. Over the next several years, we also expect that states
      will expand their efforts to implement evidence-based practices. However, we urge
      these states to implement existing evidence-based practices cautiously,
      especially with culturally diverse populations, due to the limited representation
      of ethnically diverse subjects in the research evidence on current practices. We
      strongly recommend collecting data on practice-based evidence-where effective
      interventions are routinely identified from existing practice and shared with the
      field, particularly those practices that seem effective with minority
      populations.

PMID- 15160788
TI  - The successful management of caseload stress: a case study.

PMID- 15160789
TI  - Advanced practice psychiatric nurses as a treatment resource: survey and
      analysis.

PMID- 15160790
TI  - Multidetector CT.

PMID- 15160791
TI  - Multidetector pulmonary CT angiography: advances in the evaluation of pulmonary
      arterial diseases.
AB  - Multidetector CT (MDCT) has a primary role in the evaluation of pulmonary artery
      diseases. Contrast-enhanced MDCT studies are ideally suited for assessment of
      pulmonary arterial hypertension (PAH) and pulmonary thromboembolic disease. It
      has become the primary modality to diagnose acute and chronic thromboembolic
      disease. Its role in the evaluation of pulmonary hypertension is evolving,
      allowing the radiologist to assess the presence of disease and differentiating
      intrinsic versus extrinsic pulmonary arterial pathology. An understanding of
      pulmonary CT angiography, its appropriate application, associated pitfalls,
      contrast dynamics, and thin-section CT pulmonary and cardiac anatomy is necessary
      for accurate interpretation by the radiologist. In addition to assessing the
      pulmonary arteries MDCT has the implicit advantage of thin-section lung
      parenchymal imaging, a feature that often renders an alternative diagnosis when
      symptoms of pulmonary arterial disease occur.

PMID- 15160792
TI  - Assessment of coronary artery and cardiac function using multidetector CT.
AB  - Multidetector CT is able to reconstruct artifact-less cardiac images due to
      improved temporal resolution. In this article, we review the potential benefits
      of the cardiac application of multidetector CT in the assessment of coronary
      artery and cardiac function, such as wall motion and systolic thickening. By
      applying retrospective ECG-gating, 10 phases throughout 1 cardiac cycle are
      extracted for functional analysis. Animated movies are generated by paging
      through these 2D and 3D images in cardiac phase order. Left ventricular end
      diastolic volume, end-systolic volume, and ejection fraction can also be
      generated. Using the data acquired during a single breath hold, coronary artery
      and cardiac function can be assessed by multidetector CT.

PMID- 15160793
TI  - Coronary artery disease: new insights into the pathophysiology, prevalence, and
      early detection of a monster menace.
AB  - Coronary artery disease (CAD) is the leading cause of morbidity and mortality in
      the United States and other industrialized countries. In the undeveloped world a
      similar epidemic is brewing. A new pathophysiologic paradigm has emerged, which
      assigns the mediators of inflammation a much larger role in the disease process.
      This paradigm has helped explain the unpredictable nature of many adverse
      consequences of CAD. The long latent phase of the disease, and often sudden
      initial presentation, make efforts at early detection extremely important.
      Considerable work has been devoted to identify, as well as influence,
      predisposing risk factors for developing arteriosclerosis. Novel markers of
      inflammation, like C-reactive protein, have been identified and compared to
      traditional risk factors. In addition, new imaging modalities introduce the
      possibility of screening for subclinical disease. Electron beam and multidetector
      computed tomography (CT) scanners, as well as other techniques, are emerging as
      powerful tools to detect early disease presence and allow intervention to take
      place before major clinical events occur. Advances in our understanding of the
      pathophysiology of CAD, and our ability to image the stages of silent disease
      will go hand in hand to revolutionize our approach to prevention and treatment of
      this deadly malady.

PMID- 15160794
TI  - Abdominal MDCT: liver, pancreas, and biliary tract.
AB  - Multidetector row computed tomography (MDCT) enables rapid thin-section
      acquisition of regional body anatomy. MDCT is adapted to hepatic and pancreatic
      imaging to produce, in appropriate clinical circumstances, a multipass
      multiplanar study obtained during defined circulatory phases to best outline
      vasculature and detect and characterize focal parenchymal lesions. In this
      chapter, a rational approach to hepatic and pancreatic MDCT acquisition is
      outlined with emphasis on circulatory phases and contrast material
      pharmacokinetics as well as biological characteristics of focal parenchymal
      lesions.

PMID- 15160796
TI  - Diagnostic imaging of acute thoracic injury.
AB  - In recent years, the advent of multidetector CT (MDCT) has begun to change the
      imaging approach to patients sustaining blunt or penetrating thoracic injury. The
      ability to directly detect some injuries that are often occult on chest
      radiography, such as pericardial hemorrhage, major thoracic vascular injury,
      small pneumothorax, and diaphragm tears, as well as the ability to better define
      the extent of other injuries, such as lung contusion and laceration, account for
      this transition. This article reviews current concepts of diagnostic imaging in
      acute chest trauma from both blunt force and penetrating mechanisms, emphasizing
      the spectrum of diagnostic imaging findings for various injuries, primarily based
      on multidetector MDCT.

PMID- 15160795
TI  - MDCT-imaging of peripheral arterial disease.
AB  - With the design and development of advanced computed tomography (CT) techniques
      and applications, like the newest generation of 16-detector-row CTs, CT
      angiography of the lower limb becomes a feasible tool for imaging peripheral
      vascular disease. Due to several advantages, compared with conventional digital
      subtraction angiography (DSA), including minimal invasiveness, CT angiography
      competes against diagnostic DSA in several clinical situations. 16-DCT offers the
      possibility to acquire thin slices from the diaphragm to the ankle in less than
      40 sec. Easily, a data set of 800 to 1200 transverse slices may be created. To
      use transverse reconstructions alone to read these volumetric data sets is not
      appropriate. Powerful post-processing tools for volumetric analysis are required
      so that routine interpretation can be performed as efficiently and accurately as
      transverse section review. Because of its widespread availability and
      applicability, CT angiography of the lower extremities may be applied to patients
      in a pre- or post-procedural situation and also serves as a first line modality
      in patients with acute onset of clinical symptoms. Although multidetector CT
      arteriography is rapidly achieving clinical acceptance, further studies need to
      be performed to fully evaluate the clinical value of this method of peripheral
      arterial imaging. This article reviews the current status of multidetector CT
      peripheral arteriography, including indications, technical details, image post
      processing, radiation exposure, and clinical results.

PMID- 15160798
TI  - Global health policy and free access to information.

PMID- 15160797
TI  - Multi-detector row CT imaging of blunt abdominal trauma.
AB  - CT is the imaging modality of choice to evaluate hemodynamically stable patients
      suffering blunt abdominal trauma. During the past five years, single-slice
      helical CT has been replaced by multidetector row CT (MDCT). This development has
      revolutionized cross-sectional imaging for blunt trauma patients. Volumetric
      imaging with helical CT has been a major factor supporting the nonoperative
      management of solid organ injury. Trauma centers in the United States are
      replacing single-slice helical CT scanners with state-of-the-art MDCT in suites
      proximate to the patient receiving area and with facilities for monitoring and
      maintaining physiologic support. The ability to obtain high-resolution images
      with MDCT during optimal contrast enhancement at unparalleled speed helps detect
      the presence and define the extent of injuries, and crucially, to diagnose
      hemorrhage and vascular injuries. This article describes our current imaging
      protocol with MDCT-16 (i.e., 16 detector MDCT), the spectrum of diagnostic
      findings seen in blunt abdominal injury, and the role of MDCT in the
      characterization of hemorrhage and planning injury management.

PMID- 15160799
TI  - U.S. health care spending in an international context.
AB  - Using the most recent data on health spending published by the Organization for
      Economic Cooperation and Development (OECD), we explore reasons why U.S. health
      spending towers over that of other countries with much older populations.
      Prominent among the reasons are higher U.S. per capita gross domestic product
      (GDP) as well as a highly complex and fragmented payment system that weakens the
      demand side of the health sector and entails high administrative costs. We
      examine the economic burden that health spending places on the U.S. economy. We
      comment on attempts by U.S. policymakers to increase the prices foreign health
      systems pay for U.S. prescription drugs.

PMID- 15160800
TI  - Japan's health care system: containing costs and attempting reform.
AB  - As Japan's economy declined, more intensive control of prices and even volume
      through the fee schedule, plus increases in various copayment rates, led to an
      actual reduction of medical spending in 2002 for the first time in history. To
      augment established mechanisms of cost containment, case-mix-based inclusive fees
      for inpatient care were introduced in university hospitals in 2003 and are
      planned for subacute and long-term care. However, substantial reform, including
      the introduction of market-based medicine, is not likely to occur in other areas.
      Progress in making the delivery system more accountable to patients has been
      meaningful but slow.

PMID- 15160801
TI  - Reform strategies for the English NHS.
AB  - With large funding increases planned for the next five years, England's National
      Health Service (NHS) has embarked on an ambitious program of system reform. This
      paper considers the main reform strategies now being deployed and assesses three
      potentially competing assumptions underpinning them. The first implies that
      improvement mainly requires a sufficient supply of health professionals, properly
      supported. The second advocates more hierarchical control to offset self
      interested provider behavior, and the third stresses the role of local incentives
      and accountability. How these reforms play out over the next five years will
      determine the future shape of English health care.

PMID- 15160802
TI  - Health-adjusted premium subsidies in the Netherlands.
AB  - The Dutch government has decided to proceed with managed competition in health
      care. In this paper we report on progress made with health-based risk adjustment,
      a key issue in managed competition. In 2004 both Diagnostic Cost Groups (DCGs)
      computed from hospital diagnoses only and Pharmacy-based Cost Groups (PCGs)
      computed from out-patient prescription drugs are used to set the premium
      subsidies for competing risk-bearing sickness funds. These health-based risk
      adjusters appear to be effective and complementary. Risk selection is not a major
      problem in the Netherlands. Despite the progress made, we are still faced with a
      full research agenda for risk adjustment in the coming years.

PMID- 15160803
TI  - Disease management programs in Germany's statutory health insurance system.
AB  - The introduction in 1996 of free choice among sickness funds in Germany was
      accompanied by a "risk structure compensation" (RSC) mechanism based on average
      spending by age and sex. Because chronically ill people were not adequately taken
      into account, competition for newly insured consumers concentrated on the
      healthy. The introduction in 2002 of disease management programs addresses this
      problem: Insured people in such programs are treated as a separate RSC category,
      making them a more "attractive" group that no longer generates a deficit. The
      degree of sickness fund activities and the fierce dispute with physicians are
      valid indicators that the incentives work.

PMID- 15160804
TI  - Trends in international nurse migration.
AB  - Predicted shortages and recruitment targets for nurses in developed countries
      threaten to deplete nurse supply and undermine global health initiatives in
      developing countries. A twofold approach is required, involving greater diligence
      by developing countries in creating a largely sustainable domestic nurse
      workforce and their greater investment through international aid in building
      nursing education capacity in the less developed countries that supply them with
      nurses.

PMID- 15160805
TI  - Imported care: recruiting foreign nurses to U.S. health care facilities.
AB  - As U.S. health care facilities struggle to fill current registered nurse staffing
      vacancies, a more critical nurse undersupply is predicted over the next twenty
      years. In response, many institutions are doubling their efforts to attract and
      retain nurses. To that end, foreign nurses are increasingly being sought,
      creating a lucrative business for new recruiting agencies both at home and
      abroad. This paper examines past and current foreign nurse use as a response to
      nurse shortages and its implications for domestic and global nurse workforce
      policies.

PMID- 15160807
TI  - There is no perfect health system.
AB  - Extensive research into quality of care in different countries yields no
      conclusive findings that one system is better or worse than others. Quality does
      not necessarily vary with financing mechanisms; even countries with single-payer
      systems have variations in quality. Quality is not directly related to the amount
      spent on health care, since the highest-spending country (the United States) does
      not have measurably better outcomes. Investments in the quality measurement and
      reporting systems in all countries would substantially increase the opportunities
      to learn from cross-national comparisons.

PMID- 15160806
TI  - How does the quality of care compare in five countries?
AB  - International data on quality of medical care allow countries to compare their
      performance to that of other countries. The Commonwealth Fund International
      Working Group on Quality Indicators collected data on twenty-one indicators that
      reflect medical care in Australia, Canada, New Zealand, England, and the United
      States. The indicators include five-year cancer relative survival rates, thirty
      day case-fatality rates after acute myocardial infarction and stroke, breast
      cancer screening rates, and asthma mortality rates. No country scores
      consistently the best or worst overall. Each country has at least one area of
      care where it could learn from international experiences and one area where its
      experiences could teach others.

PMID- 15160808
TI  - When things go wrong: how health care organizations deal with major failures.
AB  - Concern about patient safety, caused in part by high-profile major failures in
      which many patients have been harmed, is rising worldwide. This paper draws on
      examples of such failures from several countries to analyze how these events are
      dealt with and to identify lessons and recommendations for policy. Better systems
      are needed for reporting and investigating failures and for implementing the
      lessons learned. The culture of secrecy, professional protectionism,
      defensiveness, and deference to authority is central to such major failures, and
      preventing future failures depends on cultural as much as structural change in
      health care systems and organizations.

PMID- 15160809
TI  - Quality incentives: the case of U.K. general practitioners.
AB  - The United Kingdom is implementing major changes to the national contract for
      general practitioners (GPs). A central plank of the new arrangements is an
      ambitious scheme to reward high-quality care. Each general practice will be
      scored on 146 performance indicators according to the measured quality of care it
      delivers, and its accumulated score will determine the magnitude of the quality
      payment it receives. About 18 percent of practice earnings will be at risk. This
      paper describes the incentive scheme, discusses its potential benefits and risks,
      and draws out the implications for evaluation.

PMID- 15160810
TI  - Confronting competing demands to improve quality: a five-country hospital survey.
AB  - This paper reports on a 2003 comparative survey of hospital executives in
      Australia, Canada, New Zealand, the United Kingdom, and the United States.
      Reflecting higher spending levels, U.S. hospitals as a group stand out for
      generally more positive ratings of facilities and finances and short or no
      waiting times. Yet U.S. hospital executives are also the most negative about
      their country's health care system. Hospital executives in all five countries
      expressed concerns about staffing shortages and emergency department waiting
      times and quality. Asked about future strategies to improve quality, executives
      in all five countries expressed support for making information technology an
      investment priority.

PMID- 15160811
TI  - The general agreement on trade in services: implications for health policymakers.
AB  - The General Agreement on Trade in Services (GATS), created under the auspices of
      the World Trade Organization, aims to regulate measures affecting international
      trade in services-including health services such as health insurance, hospital
      services, telemedicine, and acquisition of medical treatment abroad. The
      agreement has been the subject of great controversy, for it may affect the
      freedom with which countries can change the shape of their domestic health care
      systems. We explain the rationale behind the agreement and discuss its scope. We
      also address the major controversies surrounding the GATS and their implications
      for the U.S. health care system.

PMID- 15160812
TI  - TRIPS and the global pharmaceutical market.
AB  - This paper reviews the international controversy over patents and access to drugs
      in developing countries and explores the implications of the 1995 Trade-Related
      Aspects of Intellectual Property Rights (TRIPS) agreement, the 2001 Doha
      Declaration, and the 2003 agreement preceding the Cancun meeting. These
      agreements do not resolve the important funding issues that developing countries
      confront as they seek access to drugs. Also, the international debate and its
      resolution will complicate the importing of foreign pharmaceuticals into the
      United States and strengthen pressures both for expanding public support of U.S.
      drug purchases and, in the long run, for political control of U.S. pharmaceutical
      pricing.

PMID- 15160814
TI  - Comprehensive versus selective primary health care: lessons for global health
      policy.
AB  - Primary health care was declared the model for global health policy at a 1978
      meeting of health ministers and experts from around the world. Primary health
      care requires a change in socioeconomic status, distribution of resources, a
      focus on health system development, and emphasis on basic health services.
      Considered too idealistic and expensive, it was replaced with a disease-focused,
      selective model. After several years of investment in vertical interventions,
      preventable diseases remain a major challenge for developing countries. The
      selective model has not responded adequately to the interrelationship between
      health and socioeconomic development, and a rethinking of global health policy is
      urgently needed.

PMID- 15160813
TI  - How do patents and economic policies affect access to essential medicines in
      developing countries?
AB  - This paper studies the relationship between patents and access to essential
      medicines. It finds that in sixty-five low- and middle-income countries, where
      four billion people live, patenting is rare for 319 products on the World Health
      Organization's Model List of Essential Medicines. Only seventeen essential
      medicines are patentable, although usually not actually patented, so that overall
      patent incidence is low (1.4 percent) and concentrated in larger markets. This
      and other results shed light on the policy dialogue among public health
      activists, the pharmaceutical industry, and governments that is often based on
      mistaken premises about how patents affect corporate revenues or the health of
      the world's poorest. Pragmatism and greater flexibility are urged, so that policy
      may better concentrate on the greater causes of epidemic mortality, which now
      pose unprecedented threats to global peace and security.

PMID- 15160815
TI  - Think globally, protect locally: a conversation with Mark McClellan.
AB  - Departing Food and Drug Administration (FDA) Commissioner Mark McClellan outlines
      the major initiatives of his sixteen-month tenure at the agency, including an
      expanded role for economic analysis in FDA policy, steps to promote "e
      prescribing" and other information technologies, broadened use of external
      advisory panels to reduce political conflict between the agency and its various
      stakeholders, and an uncompromising stance against allowing U.S. citizens to
      reimport drugs from foreign sources. McClellan's policy interests and positions
      at the FDA may offer some insight into his approach to future policy positions at
      the Centers for Medicare and Medicaid Services.

PMID- 15160816
TI  - Canadians confront health care reform.
AB  - In 2002 Canadians were less anxious about the state of their health care system
      than they were a few years earlier, when perceptions peaked that the system
      needed major reform. They expressed strong support in 2002 for maintaining the
      status quo on health care financing (that is, no user fees and no two-tier care)
      within the traditional domains of physician and hospital care. But they appeared
      more receptive to two-tier care and for-profit delivery for the newer and rapidly
      expanding domains of home care and high-tech care.

PMID- 15160818
TI  - How prepared are Americans for public health emergencies? Twelve communities
      weigh in.
AB  - Since the terrorist attacks of 11 September 2001, emergency preparedness has
      become a top priority in metropolitan areas, and some of these areas have
      received considerable federal funding to help support improvements. Although much
      progress has been made, preparedness still varies across communities, with the
      larger ones exhibiting stronger response capabilities, and some weaknesses are
      evident, particularly in the areas of communications and workforce education.
      Experience with other public health emergencies, strong leadership, successful
      collaboration, and adequate funding contributed to high states of readiness.
      Important challenges include a shortage of funding, delay in the receipt of
      federal funding, and staffing shortages.

PMID- 15160817
TI  - Place of death: U.S. trends since 1980.
AB  - Place of death is one indicator of the state of end-of-life care. We examine
      trends in national death certificate data on place of death from 1980 to 1998.
      During these years the percentage of Americans dying as hospital inpatients
      decreased from approximately 54 percent to 41 percent. About 310,000 fewer people
      died in the hospital in 1998 than if the proportion of inpatient deaths had not
      changed since 1980. For certain diseases the change was much greater. In 1980
      whites and African Americans died in the hospital in equal proportions, but in
      1998 whites died as inpatients less often than African Americans. These racial
      differences and their implications deserve further study.

PMID- 15160819
TI  - A broader vision for managed care, Part 3: The scope and determinants of
      community benefits.
AB  - Managed care plans have been encouraged to address the health of the communities
      in which they are located. This paper presents the first nationally
      representative portrait of health maintenance organizations' (HMOs') community
      benefit activities, based on survey data from 1999. We found that HMOs were
      engaged in a wider variety of community involvements than were identified in past
      legal decisions and legislation defining "community benefits" for health plans.
      The scope of community activities was broader for HMOs that enroll Medicaid
      recipients, are influenced by local business leaders, operate under nonprofit
      ownership, and are located in states with community benefit reporting laws.

PMID- 15160820
TI  - Attending death with dignity.

PMID- 15160821
TI  - So tired of life.

PMID- 15160822
TI  - Simplifying children's Medicaid and SCHIP.
AB  - The states have implemented the State Children's Health Insurance Program (SCHIP)
      in a variety of ways. We describe these choices and estimate the resulting
      enrollment impacts. Many widely adopted policies, including mail-in applications
      and twelve-month continuous eligibility, have had limited impacts. Other policies
      that increase enrollment, including presumptive eligibility and self-declaration
      of income, have not been widely adopted. SCHIP programs administered as Medicaid
      expansions have been more successful in enrolling children than either separate
      SCHIP plans or combination programs. Waiting periods, premiums, and welfare
      reform have had important negative impacts on children's program enrollment.

PMID- 15160823
TI  - Profiling the quality of care in twelve communities: results from the CQI study.
AB  - Health care quality falls far short of its potential nationally. Because care is
      delivered locally, improvement strategies should be tailored to community needs.
      This analysis from the Community Quality Index (CQI) study reports on a
      comprehensive examination of how effectively care is delivered in twelve
      metropolitan areas. We find room for improvement in quality overall and in
      dimensions of preventive, acute, and chronic care in all of these communities; no
      community was consistently best or worst on the various dimensions. Having
      concrete estimates of the extent of the gap in performance should stimulate
      community-based quality improvement efforts.

PMID- 15160824
TI  - Improving the health of Californians: effective public-private strategies for
      challenging times.
AB  - This paper summarizes the discussion that occurred at a November 2003 roundtable
      on philanthropy and health policy making. The roundtable was intended to
      stimulate a conversation about the strategic interplay of health policy and
      philanthropy in a challenging economy; to gain a richer understanding of the
      needs and expectations of funders and policymakers so that resources can be
      leveraged far more effectively; and to identify practical, collaborative
      approaches for advancing policy development and implementation. The gathering
      included more than fifty key leaders from state and national foundations; state
      policymakers; representatives from the California governor's office and key state
      health agencies and commissions; private-sector leaders; and academics.

PMID- 15160825
TI  - Outcomes-based drug coverage in British Columbia.
AB  - For the past decade the provincial drug plan in British Columbia has based the
      allocation of public subsidy on scientific standards of evidence. Coverage
      policies under B.C. PharmaCare are marked by the restriction of public subsidy
      until manufacturers provide valid evidence of a comparative health outcome
      advantage versus therapeutic alternatives. Implementing and maintaining such
      outcomes-based coverage policies has required a system of evidentiary review and
      support. Since 1994 the Therapeutics Initiative at the University of British
      Columbia has provided provincial decisionmakers with such support. We describe
      lessons from the B.C. experience for jurisdictions interested in basing coverage
      on evidence of proven comparative advantage for patients' health.

PMID- 15160826
TI  - Hospital consolidation.

PMID- 15160827
TI  - Managing conflicts of interest.

PMID- 15160828
TI  - FDA decision making.

PMID- 15160829
TI  - Drug company charity programs.

PMID- 15160830
TI  - The FTC and health care.

PMID- 15160831
TI  - Expanded capacity needed?

PMID- 15160832
TI  - Role of aldosterone blockade in managing heart failure: new and emerging
      treatment options. Introduction.

PMID- 15160833
TI  - Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic
      nervous systems in heart failure.
AB  - PURPOSE: The pathophysiology of heart failure is reviewed, with particular focus
      on the role of abnormal neurohormonal activation of the sympathetic nervous
      system and the renin-angiotensin-aldosterone axis in the pathophysiology of this
      syndrome. SUMMARY: Events preceding myocardial infarction and heart failure are
      driven in part by norepinephrine, angiotensin II, and aldosterone. The
      sympathetic nervous system likely evolved to mediate acute regulation of the
      cardiovascular system, not the sustained activation that is seen in heart
      failure. Overexpression of beta1-receptors in animal models results in decreased
      left ventricular ejection fraction and ventricular remodeling. In patients with
      systolic dysfunction, beta-blockade has improved left ventricular function and
      decreased the risk of sudden death. Chronic exposure to excess angiotensin II
      produces eccentric ventricular hypertrophy, vasoconstriction, and sodium
      retention. Angiotensin-converting enzyme (ACE) inhibition causes only a transient
      depression of aldosterone concentrations; the chronic benefit from ACE inhibition
      in patients with heart failure likely results from augmentation of bradykinin and
      not from the inhibition of angiotensin II production. Administration of
      eplerenone, a selective mineralocorticoid receptor antagonist, following
      induction of ischemic injury in animals, blocked the progressive ventricular
      dilatation and reduction in systolic function observed in control animals;
      clinical studies indicate that those findings can be translated to human
      cardiovascular disease. Overactivity of the mineralocorticoid receptor in
      cardiomyocytes could be important even in the absence of excessive levels of
      aldosterone. Clinical studies demonstrated that strategies of neurohormonal
      blockade using an ACE inhibitor, angiotensin II receptor antagonist, and beta
      blocker are ineffective in reducing circulating aldosterone in patients with
      heart failure caused by left ventricular systolic dysfunction. CONCLUSION:
      Aldosterone is a key deleterious hormone influencing all forms of cardiovascular
      disease, including hypertension, myocardial infarction, and heart failure.
      Treatment of many cardiovascular diseases should include specific antagonism of
      the adverse pathophysiologic consequences of aldosterone.

PMID- 15160834
TI  - Integrating traditional and emerging treatment options in heart failure.
AB  - PURPOSE: This paper reviews traditional approaches for the management of heart
      failure, as well as the emerging approach of using an aldosterone inhibitor.
      SUMMARY: In addition to prevention, the goals of heart failure therapy are to
      relieve symptoms, improve quality of life, slow progression of heart failure
      through both pharmacologic and nonpharmacologic therapies, minimize or prevent
      acute exacerbations, reduce hospitalizations, improve survival, favorably
      influence neurohormones, and reduce costs. Symptoms are alleviated with diuretics
      and digoxin; if digoxin is used, the target therapeutic range appears to be 0.4
      0.8 ng/mL. Large, well-controlled clinical trials have documented the
      effectiveness of angiotensin-converting enzyme (ACE) inhibitors and beta
      adrenergic blocking agents in reducing the mortality and morbidity in patients
      with heart failure ranging from post myocardial infarction left ventricular
      dysfunction to severe heart failure. Recent large studies have documented the
      effectiveness of aldosterone receptor antagonists in improving mortality and
      morbidity in patients with heart failure. There was a 30% reduction in mortality
      in patients with NYHA class III-IV heart failure when spironolactone compared
      with placebo was added to a regimen consisting of digoxin, furosemide, and an ACE
      inhibitor. A later study in which a gamma-blocker was also included in the
      regimen showed that patients with left ventricular systolic dysfunction with
      symptoms of mild heart failure following myocardial infarction taking eplerenone
      had a 15% relative reduction in all-cause mortality and a 21% reduction in sudden
      cardiac death compared with placebo. The incidence of gynecomastia was 9% and
      0.5% for spironolactone and eplerenone, respectively. CONCLUSION: The data
      support adding aldosterone receptor antagonists alongside ACE inhibitors and beta
      adrenergic blocking agents as ways to reduce mortality and morbidity in the
      treatment algorithm for heart failure. More research is needed to determine the
      usefulness of aldosterone receptor antagonists across the entire spectrum of
      heart failure.

PMID- 15160835
TI  - Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane:
      binding sites and implications for Alzheimer's disease.
AB  - The extracellular accumulation of amyloid-beta (Abeta) in neuritic plaques is one
      of the characteristic hallmarks of Alzheimer's disease (AD), a progressive
      dementing neurodegenerative disorder of the elderly. By virtue of its structure,
      Abeta is able to bind to a variety of biomolecules, including lipids, proteins
      and proteoglycans. The binding of the various forms of Abeta (soluble or
      fibrillar) to plasma membranes has been studied with regard to the direct
      toxicity of Abeta to neurons, and the activation of a local inflammation phase
      involving microglia. The binding of Abeta to membrane lipids facilitates Abeta
      fibrillation, which in turn disturbs the structure and function of the membranes,
      such as membrane fluidity or the formation of ion channels. A subset of membrane
      proteins binds Abeta. The serpin-enzyme complex receptor (SEC-R) and the insulin
      receptor can bind the monomeric form of Abeta. The alpha7nicotinic acetylcholine
      receptor (alpha7nAChR), integrins, RAGE (receptor for advanced glycosylation end
      products) and FPRL1 (formyl peptide receptor-like 1) are able to bind the
      monomeric and fibrillar forms of Abeta. In addition, APP (amyloid precursor
      protein), the NMDA-R (N-methyl-D-aspartate receptor), the P75 neurotrophin
      receptor (P75NTR), the CLAC-P/collagen type XXV (collagen-like Alzheimer amyloid
      plaque component precursor/collagen XXV), the scavenger receptors A, BI (SR-A, SR
      BI) and CD36, a complex involving CD36, alpha6beta1-integrin and CD47 have been
      reported to bind the fibrillar form of Abeta. Heparan sulfate proteoglycans have
      also been described as cell-surface binding sites for Abeta. The various effects
      of Abeta binding to these membrane molecules are discussed.

PMID- 15160836
TI  - Cosolvent-assisted oxidative folding of a bicyclic alpha-conotoxin ImI.
AB  - alpha-Conotoxin ImI is a 12-amino acid peptide, found in the venom of the marine
      snail Conus imperialis. This conotoxin is a selective antagonist of alpha7
      nicotinic acetylcholine receptors. To produce biologically active alpha-ImI,
      disulfide bonds must be formed between Cys2-Cys8 and Cys3-Cys12. Oxidative
      folding of bicyclic conotoxins, such as alpha-ImI, has been traditionally
      achieved using two-step oxidation protocols with orthogonal protection on two
      native pairs of cysteines. In this work, two alternative oxidation protocols were
      explored: (1) the recently described one-pot oxidation of t-butyl/4-methylbenzyl
      protected Cys pairs and (2) direct oxidative folding. In contrast to the first
      method, the latter one resulted in high yields of correctly folded alpha-ImI. The
      addition of organic cosolvents, such as methanol, ethanol or isopropanol into the
      folding mixture significantly increased the accumulation of the native peptide.
      This effect was also observed for another conotoxin, alpha-PnIA. It is suggested
      that cosolvent-assisted direct oxidation might be of general use for other
      bicyclic alpha-conotoxins, but efficiency should be assessed on a case-by-case
      basis.

PMID- 15160837
TI  - Synthetic human insulin 4 does not activate the G-protein-coupled receptors LGR7
      or LGR8.
AB  - In contrast to the cellular receptors for insulin and insulin-like growth factors
      that are known to be protein tyrosine kinases, those of both insulin 3 and
      relaxin have recently been identified as being members of the leucine-rich repeat
      containing G-protein coupled receptor (LGR) family, LGR8 and LGR7, respectively.
      This has prompted an examination into the possibility that they might also be
      specific for another member of the insulin superfamily, namely, insulin 4.
      Towards this aim, a two-chain peptide corresponding to the predicted primary
      structure of insulin 4 was prepared by solid phase synthesis. As conventional
      aeration and combination of the two S-reduced chains in solution at high pH
      failed to produce target product, selectively S-protected A- and B-chains were
      prepared followed by stepwise, individual formation of each of the three
      disulfides, one intramolecular within the A-chain and two intermolecular.
      Chemical characterization confirmed the purity and identity of the synthetic
      insulin 4 analogue. However, secondary structural analysis indicated that the
      peptide was devoid of tertiary conformation suggesting that the native peptide
      may well be either significantly longer in length or is similar to insulin-like
      growth factor I or II in that it is a single chain product. Screening of the
      synthetic analogue for activation of transfected cells bearing LGR7, and LGR7
      splice variant or LGR8 failed to identify a specific interaction. Thus, the in
      vivo structural identity of insulin 4 and its receptor (if any) as well as its
      potential function remains unknown.

PMID- 15160838
TI  - Synthesis and characterization of a sulfated and a non-sulfated cyclic CCK8
      analogue functionalized with a chelating group for metal labelling.
AB  - Two cyclic peptides, cyclo29,34[Dpr29, Lys34(DTPA-Glu)]-CCK8 (1) and
      cyclo29,34[Tyr27(SO3H), Dpr29, Lys34(DTPA-Glu)]-CCK8 (2), bearing the chelating
      moiety DTPA-Glu covalently bound to the Lys side chain have been synthesized by
      solid-phase methodology. The presence in compound 2 of many acidic functions
      characteristic of the chelating agent increases the lability of the sulfate group
      on the Tyr side chain. This finding suggests that prolonged acid treatments
      should be avoided during the preparation of such peptides. Sulfation of
      cyclo29,34[Dpr29, Lys34(DTPA-Glu)]-CCK8 was performed using a pyridine-SO3
      complex as reagent. This reaction has been found to be the most suitable
      synthetic strategy for obtaining compound 2 in good yield.
      Cyclo29,34[Tyr27(SO3H), Dpr29, Lys34(DTPA-Glu)]-CCK8 is a new promising CCK8
      analogue, able to coordinate radioactive isotopes of metal ions such as
      111In(III), and to bind, in a selective way, the CCKA-R receptor.

PMID- 15160839
TI  - Computational study of the conformational preferences of the (R)-8-amino
      pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane-8-carboxylic acid monopeptide.
AB  - alpha-Amino acids are important building blocks for the synthesis of a large
      number of bioactive compounds and pharmaceutical drugs. However, a literature
      survey revealed that no theoretical conformational study of alpha-amino acids
      with cage carbon frameworks has been performed to date. This paper reports the
      results of a conformational study on the (R)-8-amino
      pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane-8-carboxylic acid monopeptide
      (cage monopeptide), using molecular mechanics and ab initio methods. The in vacuo
      Ramachandran maps computed using the different parameterizations of the AMBER
      force field show the C7eq structure as the most favourable conformation, in
      contrast to the C7ax structure, that is the lowest energy conformation at the ab
      initio level. Analysis of these maps reveals the helical preference for the
      monopeptide and provides the potential for the cage residue to be incorporated
      into constrained peptide analogues.

PMID- 15160840
TI  - New analogues of laminin active fragment YIGSR: synthesis and biological activity
      in vitro and in vivo.
AB  - Eleven analogues of the laminin pentapeptide amide fragment Tyr-Ile-Gly-Ser-Arg
      NH2 (YIGSR-NH2) corresponding to a B1 chain fragment of the glycoprotein laminin
      have been synthesized by the solid phase method, and their biological activity
      has been studied in vitro by a cell adhesion assay: all of them inhibited the
      adhesion of LLC tumor cells to laminin. The analogues were found to be more
      resistant to enzymatic degradation in human serum than YIGSR-NH2 itself. Analogue
      DatIGSHar-NH2 was selected for an experimental pulmonary metastasis assay in
      vivo: it had higher antimetastatic activity than YIGSR-NH2.

PMID- 15160841
TI  - Organization of designed nanofibrils assembled from alpha-helical peptides as
      determined by electron microscopy.
AB  - Self-assembling peptides present attractive platforms for engineering materials
      with controlled nanostructures. Recently, an alpha-helical fibril forming peptide
      (alphaFFP) was designed that self-assembles into nanofibrils at acid pH. Circular
      dichroism spectroscopy, electron-microscopy and x-ray fibre diffraction data
      showed that the most likely structure of alphaFFP fibrils is a five-stranded
      coiled coil rope. In the present study, scanning transmission electron microscopy
      (STEM) was used to improve our understanding of the alphaFFP fibril structure.
      The measurements of fibril mass per length suggest that there are ten alpha
      helices in transverse sections of the fibrils. Based on the known data, it is
      proposed that a predominant fibrillar structure of alphaFFP is a dimer of alpha
      helical five stranded protofilaments wrapped around a common axis. It is shown
      that these structures have an axial dimension of 58 +/- 16 nm and a width of 4 +/
      1 nm. A small number of thin fibrils is also observed in the negative stained
      preparation and STEM images. The thin fibrils may correspond to the single
      protofilament.

PMID- 15160842
TI  - Structure-antiviral activity relationships of cecropin A-magainin 2 hybrid
      peptide and its analogues.
AB  - In order to elucidate the structure-antiviral activity relationship of cecropin A
      (1-8)-magainin 2 (1-12) (termed CA-MA) hybrid peptide, several analogues with
      amino acid substitutions were synthesized. In a previous study, it was shown that
      serine at position 16 in CA-MA hybrid peptide was very important for
      antimicrobial activity. Analogues were designed to increase the hydrophobic
      property by substituting a hydrophobic amino acid residue (S --> A, V, F or W,
      position 16) in the CA-MA hybrid peptide. In this study, the structure-antiviral
      activity relationships of CA-MA and its analogues were investigated. In
      particular, substitution of Ser with a hydrophobic amino acid, Val, Phe or Trp at
      position 16 caused a dramatic increase in the virus-cell fusion inhibitory
      activity. These results suggested that the hydrophobicity at position 16 in the
      hydrophobic region of CA-MA is important for potent antiviral activity.

PMID- 15160843
TI  - Antinematodal effect of antimicrobial peptide, PMAP-23, isolated from porcine
      myeloid against Caenorhabditis elegans.
AB  - The antinematodal activity and mechanism of a 23-mer antimicrobial peptide, PMAP
      23, derived from pig myeloid was investigated. PMAP-23 displayed a strong
      antinematodal activity against the eggs and worms of Caenorhabditis elegans. To
      investigate the antinematodal mechanism of PMAP-23, fluorescence activated flow
      cytometry and confocal laser scanning microscopy were performed. C. elegans
      treated with PMAP-23 showed higher fluorescence intensity by propidium iodide
      (PI) staining than normal cells. Confocal microscopy showed that the peptide was
      localized in the egg's shell and cell membrane. The action of the peptide against
      C. elegans membranes was examined by testing the membrane disrupting activity
      using liposome (PC/PS; 3:1, w/w). The result suggests that PMAP-23 may exert its
      antinematodal activity by disrupting the structure of the cell membrane via pore
      formation or via direct interaction with the lipid bilayers.

PMID- 15160844
TI  - Efficacy of danofloxacin in the treatment of respiratory disease in European
      cattle.
AB  - The efficacy of an injectable formulation of danofloxacin (180 mg/ml) in the
      treatment of naturally occurring bovine respiratory disease was evaluated in
      field studies on farms in France, Ireland and the United Kingdom. Cattle aged one
      week to 15 months with clinical respiratory disease were randomly allocated to
      treatment with 6 mg/kg danofloxacin or 10 mg/kg tilmicosin, administered by a
      single subcutaneous injection on day 0. A second injection of danofloxacin was
      administered on day 2, only if predefined clinical criteria were met. Mannheimia
      haemolytica, Pasteurella multocida and Haemophilus somnus were isolated from
      pretreatment nasopharyngeal swabs taken on all the farms. After the treatment,
      there was a more rapid improvement in the clinical response of the 178 animals
      treated with danofloxacin by day 2 (P < 0.01) than in the 90 treated with
      tilmicosin. For both treatments, there were similar significant (P < 0.001)
      reductions in the mean rectal temperature and severity of clinical signs of
      abnormal respiration and depression, on days 4 and 10 compared with day 0; 78.1
      per cent of the animals treated with danofloxacin and 78.5 per cent of those
      treated with tilmicosin completed the studies. Danofloxacin 18 per cent was
      clinically safe and as effective as tilmicosin in the treatment of bovine
      respiratory disease.

PMID- 15160845
TI  - Genetic analysis of European bat lyssavirus type 1 isolates from France.
AB  - European bat lyssavirus type 1a (EBLV-1a) was first identified in central France
      from a serotine bat (Eptesicus serotinus) collected at the end of 2002. Rabies
      was diagnosed by reference rabies diagnosis methods and molecular tools.
      Phylogenetic analysis of 14 viral isolates obtained from French bats infected
      with EBLV-1 between 1989 and the end of 2002 against 47 nucleoprotein sequences
      showed a north-west to east distribution of EBLV-1a virus and a south to north
      distribution of EBLV-1b virus, isolates of which could be divided into two
      groups: group 1 in north-eastern France and group 2 in central and north-western
      France.

PMID- 15160846
TI  - Myocardial necrosis in a captive binturong (Arctictis binturong).
AB  - An adult male binturong, Arctictis binturong, which had been anorexic and
      lethargic for seven days became acutely dyspnoeic and died under anaesthesia. A
      postmortem examination revealed left ventricular hypertrophy with a thrombus
      occluding the left ventricular chamber. Histological findings included moderate
      to severe multifocal, vasculocentric myocardial degeneration and necrosis with
      fibrosis replacing myocardiocytes. Escherichia coli and Proteus mirabilis were
      grown on cultures. The animal's serum vitamin E and selenium levels were
      considered adequate. The aetiology of the chronic myocardial changes could not be
      determined.

PMID- 15160847
TI  - Complete situs inversus in a two-year-old standardbred horse.

PMID- 15160848
TI  - Aelurostrongylus abstrusus infection in two cats.

PMID- 15160849
TI  - Multiple congenital portal vein anomalies in a dog.

PMID- 15160851
TI  - Research into animal diseases.

PMID- 15160850
TI  - Funding animal health and welfare.

PMID- 15160853
TI  - Euthanasia technique for chelonians.

PMID- 15160852
TI  - Progressive blindness in greyhounds.

PMID- 15160854
TI  - Histophilus somni myocarditis in cattle in the UK.

PMID- 15160855
TI  - The rationale for and background of radioimmunotherapy: an emerging therapy for B
      cell non-Hodgkin's lymphoma.
AB  - OBJECTIVES: To present the rationale for and development of radioimmunotherapy
      (RIT) for non-Hodgkin's lymphoma (NHL), which culminated in the FDA's approval of
      yttrium 90 (90Y) ibritumomab tiuxetan in February 2002. DATA SOURCES: Published
      clinical trials of 90Y ibritumomab tiuxetan and secondary literature on
      immunotherapy, RIT, and NHL. CONCLUSION: Monoclonal antibodies to the CD20
      antigen have become an accepted therapy for NHL. Factors such as the poor
      vascularization of some tumors and the variable expression of the antigen can
      mitigate the efficacy of monoclonal antibodies, which prompted the development of
      a new strategy, RIT. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of the
      background and development of RIT is essential for nurses to educate and manage
      patients with NHL.

PMID- 15160856
TI  - Efficacy and safety of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan
      (Zevalin).
AB  - OBJECTIVES: To detail recent developments pertaining to the efficacy and safety
      of radioimmunotherapy with yttrium 90 (90Y) ibritumomab tiuxetan for patients
      with B-cell non-Hodgkin's lymphoma (NHL). DATA SOURCES: Published clinical trials
      of 90Y ibritumomab tiuxetan and secondary literature on radioimmunotherapy and
      NHL. CONCLUSION: Yttrium 90 ibritumomab tiuxetan is safe and effective in the
      indicated population. It has a good safety profile and is generally well
      tolerated. It is not associated with the adverse events from conventional
      chemotherapy and external beam radiation therapy. IMPLICATIONS FOR NURSING
      PRACTICE: Nursing professionals who are aware of the efficacy and safety data
      associated with 90Y ibritumomab tiuxetan can optimize efficacy and educate
      patients and their caregivers about the regimen.

PMID- 15160857
TI  - Radiation safety with yttrium 90 ibritumomab tiuxetan (Zevalin)
      radioimmunotherapy.
AB  - OBJECTIVES: To present pertinent issues involved in radiation safety in
      radioimmunotherapy with 90Y ibritumomab tiuxetan. DATA SOURCES: Published
      clinical trials of 90Y ibritumomab tiuxetan and secondary literature on radiation
      safety and radioimmunotherapy. CONCLUSION: Radioimmunotherapy with 90Y
      ibritumomab tiuxetan is safe and effective in the indicated population, and
      radiation safety requirements for caregivers and patients are minimal. Yttrium 90
      ibritumomab is routinely and safety administered as an outpatient procedure;
      safety precautions are universal precautions, with the addition of acrylic
      shielding for the preparation and administration of the radiolabeled dose.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses play a key role in the
      multidisciplinary team. By observing universal precautions, and advising patients
      to do the same, oncology nurses may facilitate the safe and effective
      administration of the ibritumomab tiuxetan regimen.

PMID- 15160858
TI  - Educating patients about radioimmunotherapy with yttrium 90 ibritumomab tiuxetan
      (Zevalin).
AB  - OBJECTIVES: To present the relevant information for the education of patients
      with B-cell non-Hodgkin's lymphoma (NHL) who are about to undergo
      radioimmunotherapy (RIT) with yttrium 90 (90Y) ibritumomab tiuxetan. DATA
      SOURCES: Published clinical trials of 90Y ibritumomab tiuxetan and secondary
      literature on radioimmunotherapy and NHL. CONCLUSION: RIT is an emerging
      therapeutic option for patients with B-cell NHL and promises to become more
      prevalent in clinical use. Patients need to understand the rationale for and
      schedule of treatments with this regimen and the necessary ongoing laboratory
      tests for monitoring myelosuppression, as well as possible adverse events that
      might occur after treatment. IMPLICATIONS FOR NURSING PRACTICE: Nursing
      professionals should be aware of the logistics of the ibritumomab tiuxetan
      regimen and with the data associated with it to educate patients and facilitate
      patient understanding and expectations.

PMID- 15160859
TI  - Characteristics of skin surface morphology and transepidermal water loss in
      clinically normal-appearing skin of patients with atopic dermatitis: a video
      microscopy study.
AB  - In patients with atopic dermatitis (AD), it is debatable whether clinically
      normal-appearing skin is equal to non-atopic normal skin. The aim of this study
      was to quantitatively evaluate the characteristics of normal-appearing skin of
      AD. We examined the value of skin surface morphological changes using a new,
      simple, computer-assisted method with a video microscope. We also investigated
      the physiological function as represented by transepidermal water loss (TEWL)
      levels in 44 patients with AD and 15 normal controls. The morphological changes
      were represented by a variation coefficient score that reflected the irregularity
      of skin ridges, named the surface irregularity index (SII). There were
      significant differences between the normal-appearing skin of AD and non-atopic
      normal skin in both SII (P<0.001) and in TEWL (P<0.01). Especially for the SII,
      there were significant differences between AD subgroups subdivided by peripheral
      blood eosinophil count (Eo), serum lactate dehydrogenase level, and clinical
      score. TEWL values were significantly higher in the high-Eo AD group (n=15) than
      in the low-Eo AD group (n=29) (P<0.05). These findings indicate that clinically
      normal-appearing skin of AD patients with high disease activity differs from non
      atopic normal skin in both surface morphology and physiology and that these
      changes reflect the current disease activity.

PMID- 15160860
TI  - Computer-aided diagnosis of genodermatoses.
AB  - Genodermatoses are not usually easily diagnosed by inexperienced physicians. We
      developed a computer program to aid their clinical diagnoses and compared its
      accuracy rate to those of five residents in dermatology. The database of the
      program contained the clinical findings of 100 genodermatoses. Findings related
      to the skin, its appendages, mucous membranes and physiognomy were recorded in
      detail; but the involvements of other organs, only as headings. Twenty test cases
      were prepared from previously published reports. Their clinical findings were
      evaluated both by the program and five residents, who were at the end of the
      third year of their training in dermatology. The program gave the correct
      diagnosis in all of the test cases, but the residents failed to do so in one to
      seven cases. The high accuracy rate of the program suggests that it can aid
      inexperienced physicians in their clinical diagnosis of genodermatoses.

PMID- 15160861
TI  - T cell subpopulations and IL-2R in vitiligo.
AB  - Immunological alterations have been implicated in the etiopathogenesis of
      vitiligo. The aim of this study was to determine peripheral lymphocyte
      subpopulations and interleukin-2 receptor (IL-2R) in patients with vitiligo.
      Forty-five vitiligo patients (24 female, 21 male) and 34 healthy controls (11
      female, 23 male) were included into the study. Eight (17.8%) of the patients had
      the segmental type, and 37 (82.2%) had generalized vitiligo. The disease was
      active in 25 (55.6%) patients; the other 20 (44.4%) patients had static vitiligo.
      Flow cytometry was used to determine the percentages of total T-lymphocytes, B
      lymphocytes, helper/inducer T cells, suppressor/cytotoxic T cells, natural killer
      (NK) cells, activated T cells and interleukin-2 receptor (IL-2R) with the use of
      CD3, CD19, CD4, CD8, CD16, HLA-DR and CD25 monoclonal antibodies, respectively.
      The mean value of helper T cells showed a significant difference (p=0.01) between
      the two groups with the value being 32.5% in patients and 38.1% in control
      subjects. CD4/CD8 was significantly lower in vitiligo patients (p=0.04). There
      was also a statistically significant difference in the mean percentage of
      activated T cells between vitiligo patients and control subjects (4.7 and 8.1,
      respectively; p=0.001). No statistically significant differences were found when
      the values were compared between segmental and generalized vitiligo patients, or
      between active and static cases. In conclusion, T helper/inducer cells, CD4/CD8
      ratio and activated (HLA-DR+) T cells are decreased in vitiligo patients,
      suggesting a role for changes in cellular immunity.

PMID- 15160862
TI  - Calcium dobesilate (Cd) in pigmented purpuric dermatosis (PPD): a pilot
      evaluation.
AB  - Pigmented purpuric dermatosis (PPD) is a chronic disorder of unknown etiology. It
      is quite common, and no therapy is significantly effective. Calcium dobesilate
      (Cd) has been tried successfully in many vascular disorders. The aim of this
      study was to evaluate the usefulness and efficacy of Cd in PPD. Nine male
      patients (7 with Schamberg's and 1 each with lichenoid dermatosis of Gougerot and
      Blum and lichen aureus) were given Cd 500 mg twice daily for two initial weeks
      and then 500 mg once daily for a total period of three months. All the patients
      were followed up for one year after cessation of therapy. The improvement was
      moderate in 11.11% and mild in 66.67% of cases; 22.22% did not show any
      improvement. New lesions stopped appearing in two weeks in all patients, and
      itching also improved in symptomatic cases without any significant side effects.
      Based upon the results of this pilot study we recommend Cd as the first line
      therapy for PPD.

PMID- 15160864
TI  - Unilateral nevoid telangiectasia.
AB  - Unilateral nevoid telangiectasia is a cutaneous condition consisting of
      congenital or acquired patches of superficial telangiectases in a unilateral
      linear distribution. Unilateral nevoid telangiectasia has been associated with
      elevations of blood estrogen levels and/or an increased number of estrogen
      receptors in the involved skin. We present a hepatitis-B carrier case with
      unilateral nevoid telangiectasia on the face and the right side of the neck; she
      had normal blood estrogen and a normal number of estrogen receptors in the
      involved skin.

PMID- 15160863
TI  - Clinical and pharmacokinetic studies of continuous itraconazole for the treatment
      of onychomycosis.
AB  - Itraconazole, a triazole antifungal agent, has been widely used for onychomycosis
      with high cure rates. Unchanged itraconazole and a major metabolite hydroxy
      itraconazole reach the nail with a strong affinity for keratin. The aim of this
      study was to elucidate clinical effectiveness and pharmacokinetic profiles of a 6
      month continuous itraconazole treatment at a daily dose of 100 mg. Nail growth,
      the decrease in nail turbidity, and the nail concentrations of unchanged- and
      hydroxy-itraconazole were investigated. The affected nails we examined
      demonstrated nail growth proportional to the decrease in turbidity and a quick
      increase in drug concentration with a long duration of a high concentration after
      cessation. Our results support the hypothesis that this continuous therapy is a
      good modality for onychomycosis.

PMID- 15160865
TI  - Morbihan's disease: treatment with CO2 laser blepharoplasty.
AB  - Morbihan's disease is a rare condition characterized by chronic persistent
      erythema and edema of the upper half of the face. Therapeutic regimens such as X
      ray irradiation, lymphatic massage, interferon gamma injections, antihistamines,
      and high-dose antibiotics are often unsatisfactory. Promising results in some
      patients have been achieved by a systemic combination therapy of isotretinoin
      with ketotifen or clofazimine. Excision of redundant edematous tissue may be an
      alternative. We present a 67-year-old Caucasian patient with a two-year history
      of right lower and upper eyelid swelling and erythema. Systemic therapies with
      corticocosteroids and antibiotics were not successful, but CO2 laser
      blepharoplasty led to good cosmetic results with marked improvement of visual
      impairment and no recurrence during the six-month follow-up period.

PMID- 15160866
TI  - Swan-neck deformity and paresthesia following giant orf.
AB  - Orf is a zoonotic infection caused by a parapoxvirus that primarily infects sheep
      and goats. Human orf infection can take place when abraded skin comes into
      contact with infected animals. It occurs most commonly on the index finger. The
      characteristic lesion resembles a tumor and resolves spontaneously, usually
      without any complications. However, rare complications such as lymphangitis,
      adenitis, erythema multiforme, erysipelas, papulovesicular eruption, Pseudomonas
      aeruginosa infection, and bullous pemphigoid have been reported. Herein, we
      report a case of giant orf causing swan-neck deformity and paresthesia. These
      complications have not been previously reported in the literature.

PMID- 15160867
TI  - Leprosy with Guillain Barre Syndrome: a new neurologic manifestation?
AB  - A 19-year-old female patient of lepromatous leprosy with Type II reaction, on
      multidrug therapy and prednisolone, presented with acute onset flaccid
      quadriparesis. The cerebrospinal fluid examination revealed albumino-cytologic
      dissociation. Nerve biopsy showed infiltration with lepra bacilli, features of
      vasculitis, and demyelination. There were no other identifiable precipitating
      factors for Guillain Barre Syndrome in this patient. Her condition improved
      without any steroid therapy. This case emphasizes the hypothesis that cell injury
      caused by Type II reaction can expose neural antigens and incite an autoimmune
      reaction in the form of Guillain Barre Syndrome.

PMID- 15160869
TI  - Bilateral lichen striatus.
AB  - We describe a very rare case of bilateral lichen striatus on the lower
      extremities with a history of more than ten years. Histopathologically, the
      lesions demonstrated a lichenoid tissue reaction with foci of spongiosis and
      perivascular inflammatory cell infiltration. In addition, the finding of
      lymphocytic infiltrations around the eccrine duct was observed. They were treated
      successfully with topical application of corticosteroid ointment. To the best of
      our knowledge, no other lichen striatus case has been reported with bilateral
      distribution and such long-term persistence.

PMID- 15160868
TI  - A case of multifocal lupus vulgaris that preceded pulmonary tuberculosis in an
      immune compromised patient.
AB  - We describe the rare case of a Japanese male with multifocal lupus vulgaris that
      preceded asymptomatic pulmonary tuberculosis and adult T-cell leukemia/lymphoma
      (ATL). He visited our hospital with multiple reddish plaques and erythema of 4-12
      months duration. A skin biopsy revealed non-caseating epithelioid granulomas.
      Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR)
      hybridization from a skin biopsy specimen and was also isolated from a culture of
      the skin biopsy sample. The result of chest roentogenography was compatible with
      pulmonary tuberculosis. In addition, the diagnosis of ATL was based upon the
      presence of atypical lymphocytes with convoluted nuclei in his peripheral blood
      and a positive anti-ATL antibody reaction. Cases of cutaneous tuberculosis
      presenting with unusual clinical features may be on the increase, accompanying
      the spread of tuberculosis in immunosuppressed patients, including those with ATL
      and acquired immunodeficiency syndrome (AIDS).

PMID- 15160870
TI  - Giant suspensory lipoma with calcification.
AB  - A seventy-four-year-old woman presented with a giant lipoma suspended from her
      left upper arm. The surgically removed tumor weighed 2,600 g and included
      calcified areas in its periphery. Our histologic observations suggested that the
      calcification was generated in association with degenerated fat.

PMID- 15160871
TI  - Allergic contact dermatitis with spreading over extensive regions due to topical
      use of 5% bufexamac ointment.

PMID- 15160872
TI  - Cutaneous eosinophilic vasculitis in a patient with Kimura's disease.

PMID- 15160873
TI  - A case of lichen sclerosus et atrophicus with marked fibrosis in the dermis:
      analysis of fibrogenetic cytokines by reverse transcriptase-polymerase chain
      reaction.

PMID- 15160874
TI  - Twenty nail anonychia due to lichen planus.

PMID- 15160875
TI  - Symmetrical melanonychia of the thumbnails associated with PUVA in psoriasis.

PMID- 15160876
TI  - A case of cutaneous Mycobacterium chelonae infection successfully treated with a
      combination of minocycline hydrochloride and thermotherapy.

PMID- 15160877
TI  - [Overview: signals controlling stem cell systems].

PMID- 15160878
TI  - [Signaling maintaining pluripotency in ES cells].

PMID- 15160879
TI  - [Germline stem cells and their niches].

PMID- 15160880
TI  - [Mechanism of neural stem cell fate specification].

PMID- 15160881
TI  - [Stem cells in the mammalian hair follicle].

PMID- 15160882
TI  - [Mechanisms controlling the fate of hematopoietic stem cells].

PMID- 15160883
TI  - [Stem cell systems in skeletal muscle].

PMID- 15160884
TI  - [Reconsideration of phytochrome signal transduction].

PMID- 15160885
TI  - [Novel lysine biosynthesis: a key to elucidate evolution of metabolic and
      biosynthetic pathways].

PMID- 15160887
TI  - [Bioinformatics in medicine].

PMID- 15160886
TI  - [SARS, pandemic influenza, avian influenza: quest for missing link].

PMID- 15160888
TI  - [Patent search essential for researchers].

PMID- 15160889
TI  - [An association between plasma levels of 8-isoprostane and alcohol drinking
      habits in Japanese volunteers].
AB  - Lipid peroxidation and oxidative stress may play a certain role in the
      pathogenesis of pressure-induced atherosclerosis, and alcohol related diseases.
      Recently, 8-isoprostane in biological fluids has been reported to be a reliable
      marker for lipid peroxidation and oxidative stress in vivo. In the present study,
      we developed an ELISA method for 8-isoprostane which has high sensitivity, intra-
      and inter-assay reproducibility and wide dynamic assay range. Using this method,
      we examined the effects of drinking and smoking habits on plasma levels of 8
      isoprostane in healthy subjects. A total of 157 apparently healthy volunteers was
      assayed for plasma 8-isoprostane. Subjects were divided into three groups
      according to their alcohol consumption. Group I is non- or few-drinkers, Group II
      includes subjects who drink once or twice a week, and subjects of Group III
      intake 3 to 5 times a week or almost every day. In addition, the same population
      was divided into two groups, 96 non-smokers and 61 smokers. Plasma 8-isoprostane
      was extracted with ODS gel followed by NH2 Sep-Pak column. The 8-isoprostane
      fractions thus separated were assayed by a commercial ELISA kit (Cayman
      Chemical). The plasma 8-isoprostane was estimated to be 20.9 +/- 93 pg/ml in a
      total of 157 volunteers (83 male, 74 female). The plasma 8-isoprostane levels
      were elevated in the Group III (26.6 +/- 9.5 pg/ml) compared with Group I (20.3
      +/- 6.1 pg/mL, p<0.0001) and Group II (20.9 +/- 5.7 pg/ml, p<0.001). Significant
      increase of the plasma 8-isoprostane was observed only in habitual drinkers of
      females, but not in those of males. On the other hand, no significant difference
      of the plasma 8-isoprostane levels were observed between non-smokers (21.5 +/-
      7.3 pg/ml) and smokers (22.8 +/- 7.4 pg/ml, p>0.05). We suppose that plasma 8
      isoprostane may increase in the habitual drinkers due to the oxidization stress
      induced by alcohol intake, and it may become a useful marker to estimate drinking
      habit

PMID- 15160890
TI  - [A study on effectiveness of recovery from drug dependence by participates with
      "DARC"].
AB  - The purpose of this study is to make clear changes to participate in "DARC". For
      this purpose, we made research to use the same measure of previous study for DARC
      members at fifteen sites in Japan. As a result we found characteristic changes of
      drug dependents those who participate in DARC. Between terms of drug abuse and
      terms of participate in DARC, we can find weak positive correlation coefficient
      (R=.387**). People, whose terms of drug abuse are long, have tendencies to DARC
      participation for a long time. But there is also a tendency that the longer a
      person DARC participation, the longer he or she quit drugs. On the other hand,
      there is no correlation coefficient between terms of drug free and those of drug
      abuse. From this fact, we find that it is not only the short term drug dependent
      who quit drugs. The recovery of drug dependents in DARC is caused through life
      experiences on trust in fellow members. It is not a straight path but it is
      suggested that the drug free dose not change dramatically in one or two years.
      The changes in these years are the crossroad of re-abuse later, or the turning
      point to recover and to continue the drug free. The anxieties about life in these
      years make questions for meanings of life, and this is a chance to make
      possibilities for choices of new life not to have drugs. In dependents those who
      are recovering to DRAC participation, they make fails over again, however, we
      think the changes of spirituality through DARC participation.

PMID- 15160891
TI  - [A study of factors effecting on an observation time needed for outpatient
      treatment of acute alcohol intoxication in Japan].
AB  - The purpose of this study was to investigate the factors effecting on an
      observation time needed for outpatient treatment of acute alcohol intoxication.
      Subjects were 181 patients with acute alcohol intoxication who visited at the
      Center of Critical Care Medicine of St. Luke's International Hospital from June
      1999 to May 2000. One of 181 patients was admitted as an inpatient. The mean
      observation time of 180 outpatients was about 3 hours. Ninety-nine outpatients
      (55%) needed observation time less than 3 hours. High level of Blood Alcohol
      Concentration (BAC), moderate consciousness disorder (Japan Coma Scale; JCS 10
      30), and severe consciousness disorder (JCS 100-300) were significant factors to
      increase observation time more than 3 hours. Gender and age were not significant
      factors associated with more-than-3-hour observation time. Observation time of
      mild consciousness disorder (JCS 1-3) was significantly decreased against that of
      clear consciousness (JCS 0). Effects of acetaldehyde might be related to
      elongation of the observation time among clear consciousness patients. Medical
      resources of emergency medicine in Japan are not enough in some cases (such as
      few beds and small numbers of staffs), and it is occasionally difficult for
      patients to stay at a emergency unit for a long time. And the number of
      hospitalization for acute alcohol intoxication is likely to increase in Japan.
      Consideration on the attributes, such as BAC or patient's consciousness,
      associated with observation time of outpatient treatment might be useful to
      reduce the number of hospitalization and the cost of medical care for acute
      alcohol intoxication in emergency medicine.

PMID- 15160892
TI  - [Effect of ethanol on neurogenic vascular contraction in rat superior mesenteric
      artery].

PMID- 15160894
TI  - Spatial pattern of ecosystem function and ecosystem conservation.
AB  - The spatial pattern of ecosystem function can affect ecosystem conservation.
      Ecosystem functions are often heterogeneous spatially due to physical and
      biological factors. We can influence ecosystem functions by changing the spatial
      patterns of the physical and biological elements of an ecosystem and regulating
      their combinations. The variation-position effect highlights a phenomenon
      resulting from the spatial pattern of ecosystem function. The effect shows that
      the identical variation of a factor may produce different effects on the over-all
      situation when this variation occurs in a different spatial position. In a
      watershed of the Yangtze River, water retention is a primary ecosystem function.
      The variation-position effect for water retention capacity occurs in the
      watershed because of the spatial heterogeneity in vegetation, soil, and slope.
      The change of vegetation that occurs in a complex can affect the overall
      situation of water retention, and the effect can be different due to the change
      occurring in the position holding different vegetation-soil-slope complex. To
      improve the ecosystem in the watershed and to meet the social needs for the
      ecosystem function of water retention, a strategy called "ecosystem function and
      spatial pattern-based forest extension" was proposed to conserve forests. The
      implementation of the strategy enables the watershed to attain the maximum
      effective increase in water retention capacity.

PMID- 15160893
TI  - Evaluating ecosystem management capabilities at the local level in Florida:
      identifying policy gaps using geographic information systems.
AB  - Because ecosystem approaches to management adhere to ecological systems rather
      than human-defined boundaries, collaboration across jurisdiction, agencies, and
      land ownership is often necessary to achieve effective management of
      transboundary resources. Local natural resource and land use planners
      increasingly recognize that while ecosystem management requires looking beyond
      specific jurisdictions and focusing on broad spatial scales, the approach will
      partly be implemented at the local level with the coordination of local policies
      across larger landscapes. This article evaluates the collective capabilities of
      local jurisdictions to manage large transboundary ecological systems in Florida.
      Specifically, it combines plan evaluation with geographic information systems
      (GIS) techniques to map, measure, and analyze the existing mosaic of management
      across selected ecosystems in the southern portion of the State. Visual and
      statistical results indicate significant gaps in the management framework of
      southern Florida that, if filled, could achieve a greater level of consistency
      and more complete coverage of ecosystem management policies. Based on the spatial
      distribution of 58 ecosystem management indicators, notable gaps persist in the
      southwest coast, southeast coast, and central Everglades ecosystems, particularly
      for wildlife corridors and collaboration with neighboring jurisdictions. We also
      test for spatial autocorrelation of ecosystem planning scores and find that local
      jurisdictions with strong ecosystem management capabilities tend to cluster
      within specific ecosystems. Based on the findings, we make recommendations on how
      and where local plans can be strengthened to more effectively attain the
      objectives of ecosystem approaches to management.

PMID- 15160895
TI  - Impacts of camping on vegetation: response and recovery following acute and
      chronic disturbance.
AB  - Experiments with controlled levels of recreational camping were conducted on
      previously undisturbed sites in two different plant communities in the subalpine
      zone of the Wind River Mountains, Wyoming, USA. The plant communities were
      coniferous forest with understory dominated by the low shrub Vaccinium scoparium
      and a riparian meadow of intermixed grasses and forbs, of which Deschampsia
      cespitosa was most abundant. Sites were camped on at intensities of either one or
      four nights per year, for either one (acute disturbance) or three consecutive
      years (chronic disturbance). Recovery was followed for three years on sites
      camped on for one year and for one year on sites camped on for three years.
      Reductions in vegetation cover and vegetation height were much more pronounced on
      sites in the forest than on sites in the meadow. In both plant communities,
      increases in vegetation impact were not proportional to increases in either years
      of camping or nights per year of camping. Close to the center of campsites, near
      maximum levels of impact occurred after the first year of camping on forested
      sites and after the second year on meadow sites. Meadow sites recovered
      completely within a year, at the camping intensities employed in the experiments.
      Forest sites, even those camped on for just one night, did not recover completely
      within three years. Differences between acute and chronic disturbance were not
      pronounced.

PMID- 15160896
TI  - A GIS model of subsurface water potential for aquatic resource inventory,
      assessment, and environmental management.
AB  - Biological, chemical, and physical attributes of aquatic ecosystems are often
      strongly influenced by groundwater sources. Nonetheless, widespread access to
      predictions of subsurface contributions to rivers, lakes, and wetlands at a scale
      useful to environmental managers is generally lacking. In this paper, we describe
      a "neighborhood analysis" approach for estimating topographic constraints on
      spatial patterns of recharge and discharge and discuss how this index has proven
      useful in research, management, and conservation contexts. The Michigan Rivers
      Inventory subsurface flux model (MRI-DARCY) used digital elevation and hydraulic
      conductivity inferred from mapped surficial geology to estimate spatial pattems
      of hydraulic potential. Model predictions were calculated in units of specific
      discharge (meters per day) for a 30-m-cell raster map and interpreted as an index
      of potential subsurface water flux (shallow groundwater and event through-flow).
      The model was evaluated by comparison with measurements of groundwater-related
      attributes at watershed, stream segment, and local spatial scales throughout
      Lower Michigan (USA). Map-based predictions using MRI-DARCY accounted for 85% of
      the observed variation in base flow from 128 USGS gauges, 69% of the observed
      variation in discharge accrual from 48 river segments, and 29% of the residual
      variation in local groundwater flux from 33 locations as measured by hyporheic
      temperature profiles after factoring out the effects of climate. Although it does
      not incorporate any information about the actual water table surface, by
      quantifying spatial variation of key constraints on groundwater-related
      attributes, the model provides strata for more intensive study, as well as a
      useful spatial tool for regional and local conservation planning, fisheries
      management, wetland characterization, and stream assessment.

PMID- 15160897
TI  - Optimizing liquid effluent monitoring at a large nuclear complex.
AB  - Effluent monitoring typically requires a large number of analytes and samples
      during the initial or startup phase of a facility. Once a baseline is
      established, the analyte list and sampling frequency may be reduced. Although
      there is a large body of literature relevant to the initial design, few, if any,
      published papers exist on updating established effluent monitoring programs. This
      paper statistically evaluates four years of baseline data to optimize the liquid
      effluent monitoring efficiency of a centralized waste treatment and disposal
      facility at a large defense nuclear complex. Specific objectives were to: (1)
      assess temporal variability in analyte concentrations, (2) determine operational
      factors contributing to waste stream variability, (3) assess the probability of
      exceeding permit limits, and (4) streamline the sampling and analysis regime.
      Results indicated that the probability of exceeding permit limits was one in a
      million under normal facility operating conditions, sampling frequency could be
      reduced, and several analytes could be eliminated. Furthermore, indicators such
      as gross alpha and gross beta measurements could be used in lieu of more
      expensive specific isotopic analyses (radium, cesium-137, and strontium-90) for
      routine monitoring. Study results were used by the state regulatory agency to
      modify monitoring requirements for a new discharge permit, resulting in an annual
      cost savings of US dollars 223,000. This case study demonstrates that statistical
      evaluation of effluent contaminant variability coupled with process knowledge can
      help plant managers and regulators streamline analyte lists and sampling
      frequencies based on detection history and environmental risk.

PMID- 15160898
TI  - Components of the total water balance of an urban catchment.
AB  - A daily model was used to quantify the components of the total urban water
      balance of the Curtin catchment, Canberra, Australia. For this catchment, the
      mean annual rainfall was found to be three times greater than imported potable
      water, and the sum of the output from the separate stormwater and wastewater
      systems exceeded the input of imported potable water by some 50%. Seasonal and
      annual variations in climate exert a very strong influence over the relative
      magnitude of the water balance components; this needs to be accounted for when
      assessing the potential for utilizing stormwater and wastewater within an urban
      catchment.

PMID- 15160899
TI  - Assessing biological integrity using freshwater fish and decapod habitat
      selection functions.
AB  - Comparison between the number of taxa observed and the number expected in the
      absence of human impact is an easily understood and ecologically meaningful
      measure of biological integrity. This approach has been successfully applied to
      the assessment of the biological quality of flowing water sites using
      macroinvertebrates with the river invertebrate and classification system
      (RIVPACS) and its derivatives. In this paper, we develop a method similar to the
      RIVPACS predictive model approach to assess biological integrity at flowing-water
      sites using freshwater fish and decapod assemblages. We extend the RIVPACS
      approach by avoiding the biotic classification step and model each of the
      individual species separately. These assemblages were sampled at 118 least
      impacted (reference) sites in the Auckland region, New Zealand. Individual
      discriminant models based on the presence or absence of the 12 most common fish
      and decapod species were developed. Using the models, predictions were made using
      environmental measures at new sites to yield the probability of the capture of
      each of the 12 species, and these were combined to predict the assemblage
      expected at sites. The expected assemblage was compared to that observed using an
      observed over expected ratio (O/E). The models were evaluated using a number of
      internal tests including jackknifing, data partitioning, and the degree to which
      O/E values differed between reference sites and a set of sites perceived to be
      impaired by human impacts.

PMID- 15160900
TI  - Ecological impact assessment in data-poor systems: a case study on metapopulation
      persistence.
AB  - Legislation on the protection of biodiversity (e.g., European Union Habitat and
      Bird Directives) increasingly requires ecological impact assessment of human
      activities. However, knowledge and understanding of relevant ecological processes
      and species responses to different types of impact are often incomplete. In this
      paper we demonstrate with a case study how impact assessment can be carried out
      for situations where data are scarce but some expert knowledge is available. The
      case study involves two amphibian species, the great crested newt (Triturus
      cristatus) and the natterjack toad (Bufo calamita) in the nature reserve the
      Meinweg in the Netherlands, for which plans are being developed to reopen an old
      railway track called the Iron Rhine. We assess the effects of this railway track
      and its proposed alternatives (scenarios) on the metapopulation extinction time
      and the occupancy times of the patches for both species using a discrete-time
      stochastic metapopulation model. We quantify the model parameters using expert
      knowledge and extrapolated data. Because of our uncertainty about these parameter
      values, we perform a Monte Carlo uncertainty analysis. This yields an estimate of
      the probability distribution of the model predictions and insight into the
      contribution of each distinguished source of uncertainty to this probability
      distribution. We show that with a simple metapopulation model and an extensive
      uncertainty analysis it is possible to detect the least harmful scenario. The
      ranking of the different scenarios is consistent. Thus, uncertainty analysis can
      enhance the role of ecological impact assessment in decision making by making
      explicit to what extent incomplete knowledge affects predictions.

PMID- 15160901
TI  - Evaluation of generic types of drilling fluid using a risk-based analytic
      hierarchy process.
AB  - The composition of drilling muds is based on a mixture of clays and additives in
      a base fluid. There are three generic categories of base fluid--water, oil, and
      synthetic. Water-based fluids (WBFs) are relatively environmentally benign, but
      drilling performance is better with oil-based fluids (OBFs). The oil and gas
      industry developed synthetic-based fluids (SBFs), such as vegetable esters,
      olefins, ethers, and others, which provide drilling performance comparable to
      OBFs, but with lower environmental and occupational health effects. The primary
      objective of this paper is to present a methodology to guide decision-making in
      the selection and evaluation of three generic types of drilling fluids using a
      risk-based analytic hierarchy process (AHP). In this paper a comparison of
      drilling fluids is made considering various activities involved in the life cycle
      of drilling fluids. This paper evaluates OBFs, WBFs, and SBFs based on four major
      impacts--operations, resources, economics, and liabilities. Four major activities
      -drilling, discharging offshore, loading and transporting, and disposing onshore-
      cause the operational impacts. Each activity involves risks related to
      occupational injuries (safety), general public health, environmental impact, and
      energy use. A multicriteria analysis strategy was used for the selection and
      evaluation of drilling fluids using a risk-based AHP. A four-level hierarchical
      structure is developed to determine the final relative scores, and the SBFs are
      found to be the best option.

PMID- 15160902
TI  - Development of lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its
      relationship to Fas gene mutations.
AB  - Autoimmune Lymphoproliferative Syndrome (ALPS) is generally the result of a
      mutation in genes associated with apoptosis, like Fas, Fas ligand, Casp 8 and
      Casp 10. As a result, the normal homeostasis of T- and B-lymphocytes is disturbed
      and a proliferation of polyclonal T lymphocytes occurs. This leads to
      hepatosplenomegaly and lymphadenopathy and in most patients also to autoimmune
      phenomena like anemia and thrombocytopenia. The proliferating T cells are
      TCRalphabeta and/or TCRgammadelta positive but lack both CD4 and CD8. Hence they
      are termed double negative (DN) T cells. In addition, there is an increase of CD5
      positive B cells. Individuals with germline mutations in the Fas gene have a high
      risk to develop non Hodgkin lymphomas (x 14) as well as Hodgkin lymphomas (x 51),
      in particular NLP Hodgkin lymphoma. Somatic mutations of Fas are frequently
      acquired during the normal germinal center reaction. Non Hodgkin lymphomas carry
      somatic mutations of the Fas gene in 11% and of the Casp 10 gene in 14.5% of the
      patients. In Hodgkin lymphomas, Fas mutations can be demonstrated in Reed
      Sternberg cells in 10-20% of the patients. These data implicate a role for Fas
      mediated apoptosis in preventing lymphomas. Inherited defects in receptor
      mediated lymphocyte apoptosis represent a risk factor for lymphomas and somatic
      mutations of these genes may also play a role in the development and/or
      progression of lymphomas.

PMID- 15160903
TI  - Evolution of clonal cytogenetic abnormalities in aplastic anemia.
AB  - Prior to the introduction of effective therapies, the high mortality rates of
      severe aplastic anemia (AA) precluded recognition of late complications of this
      disease. Once the survival of AA improved, observation of clonal evolution raised
      questions as to whether the development of secondary myelodysplastic syndrome
      (MDS) is a part of the extended natural history of the disease or is related to
      the therapies applied. Clinical features of myelodysplasia and AA can overlap,
      and typical MDS may evolve as a complication of AA. Common pathophysiologic
      elements operate in these diseases and are subject to many studies and theories
      as to what mechanisms in AA may lead to the late evolution of MDS. Similarly, AA
      has been hypothesized to be a reflection of an over-reactive immune response
      triggered by the appearance of genetically altered and/or phenotypically abnormal
      dysplastic clones. Hypocellular variants of myelodysplasia and responsiveness of
      certain forms of MDS to immunosuppressive regimens serve as the most appealing
      examples of the intricate and close pathophysiologic relationship of this disease
      with AA. The diagnosis of clonal evolution in the course of AA can be obvious if
      secondary cytopenia involves hypercellularity and a high percentage of blasts. In
      addition, the occurrence of a new karyotypic defect objectively heralds the
      progression of disease to MDS. However, the diagnostic imprecision of dysplasia
      recognition in the context of marrow hypocellularity, inability to obtain
      informative cytogenetics, and a high proportion of MDS cases with normal
      karyoptype have hampered studies designed to determine the frequency and timing
      of MDS evolution in AA. In addition, the diagnostic criteria and definitions used
      are not unified. While some centers recognize that the abnormal karyotype does
      not preclude the diagnosis of AA; in others, the diagnosis of AA includes the
      presence of normal karyoptype. Many typical features of dysplastic evolution in
      AA have been clarified. For example, karyotypes most frequently encountered in
      MDS secondary to AA involve chromosomes 6, 7 and 8. The evolution rates seem to
      be in the range of 10-15% in 10 years, but there are no predictive clues as to
      which patients are at greatest risk for this complication. Study of the
      mechanisms of clonal evolution in AA may help understand the pathophysiology of
      other forms of MDS and leukemia and also the mechanisms of antileukemic
      surveillance. Clinically, identification of patients at increased risk for clonal
      complications may influence the choice of therapies applied.

PMID- 15160904
TI  - Stem cell transplantation for peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCL) consist of many subtypes with variable
      clinical presentation. Long-term prognosis of most subtypes is unfavorable and
      novel therapeutic approaches are needed. This review attempts to summarize what
      is known on the feasibility and efficacy of high-dose therapy supported by stem
      cell transplantation (SCT) in PTCL. In patients with relapsed or refractory PTCL,
      the outcome of autologous SCT (ASCT) seems to be comparable to that of patients
      with aggressive B-cell lymphomas. Although excellent treatment results have been
      encountered with ASCT in patients with anaplastic large cell lymphoma (ALCL), the
      superiority of this approach over chemotherapy alone needs confirmation in
      randomized studies. In less favorable subtypes (e.g. alk-negative ALCL, PTCL not
      otherwise specified, enteropathy-associated T-cell lymphoma, and
      angioimmunoblastic T-cell lymphoma) high-dose consolidation of the first
      remission should be studied in prospective trials. Minimal experience is
      currently available on allogeneic SCT in patients with PTCL. Given the high
      relapse rate after ASCT in high-risk patients and potential for graft-vs.
      lymphoma effect, also this approach should be studied. Due to rarity of PTCL,
      international collaboration is mandatory in order to study the various aspects of
      SCT in this patient population.

PMID- 15160905
TI  - Allogeneic transplantation of CD34+ selected hematopoietic cells--clinical
      problems and current challenges.
AB  - Since G-CSF mobilized peripheral blood has become the major source of
      hematopoietic cells (PBSC) for allogeneic transplantation of patients with
      hematological malignancies, new technologies of T-cell depletion were developed
      to reduce the risk of graft-versus-host disease. CD34+ selection by
      immunomagnetic separation has been shown to be the most effective method to
      achieve a 3-4 log depletion of T-cells while preserving the high number of
      hematopoietic progenitors in the graft. The high number of CD34+ cells contained
      in the positive fraction have allowed to facilitate engraftment from sibling
      donors matched for only one haplotype. In addition, studies in pediatric
      recipients have shown that high numbers of hematopoiteic progenitors infused can
      lead to timely recovery of T- and B-cells in the first year after
      transplantation. Positive results have also been reported in patients with
      chronic myelogenous leukemia who had received CD34+ selected PBSC from HLA
      identical sibling donors and subsequent infusions of donor T-cells to establish
      graft-versus-leukemia effects. On the other hand, studies performed in adults
      with advanced leukemia receiving CD34+ selected PBSC from haploidentical or
      unrelated donors demonstrated an increased risk for graft-rejection, relapse and
      late opportunistic infections. Future efforts will have to concentrate on the
      restoration of cellular immunity by either adaptively transferring antigen
      specific effector cells or by studying the use of cytokines like interleukin-7.
      Although these question have not been resolved yet, allogeneic transplantation of
      highly purified CD34+ PBSC has become an therapeutic option for patients who are
      at high-risk for severe GvHD.

PMID- 15160907
TI  - Current molecular diagnostic approaches to systemic infections with aspergillus
      species in patients with hematological malignancies.
AB  - Within the recent years, novel molecular methods, especially PCR assays, have
      been developed to improve the diagnosis of invasive aspergillosis in patients
      with malignant hematological diseases being at high risk for this life
      threatening infection. Early diagnosis and treatment are essential for adequate
      therapeutical management, which however, often remains difficult since most of
      the diagnostic tools used clinically at present either lack specificity or
      acceptable sensitivity. The clinical value, advantages and remaining problems of
      recently developed molecular approaches to detect the emerging fungal pathogen
      are reviewed.

PMID- 15160906
TI  - The prognostic value of CD38 expression and its quantification in B cell chronic
      lymphocytic leukemia (B-CLL).
AB  - A large number of prognostic factors are available to help predict the outcome of
      patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These
      include clinical stage, leukemic cell morphology, lymphocyte doubling time, the
      pattern of infiltration in bone marrow trephine biopsies, cytogenetic
      abnormalities, p53 function and serum factors such as beta-2 microglobulin. Two
      recently described major prognostic factors are immunoglobulin heavy chain
      variable region (IgVH) mutation status and cell membrane expression of CD38.
      These are both highly significant independent prognostic factors, but are not
      closely correlated. Whereas IgVH mutational status is a time consuming and
      demanding technique, only available in a limited number of centres, CD38
      expression by flow cytometry is relatively simple and rapidly obtained in most
      diagnostic laboratories. The predictive value of CD38 expression is enhanced by
      measurement of antigen density in terms of antibody binding capacity (ABC) rather
      than as the percentage of cells expressing the antigen. ABC correlates closely
      with relative median fluorescence (RMF), a parameter which is even more simply
      and cheaply obtained by flow cytometry. One of these methods of determining CD38
      expression should be employed routinely. Recent work suggests that membrane ZAP
      70 expression determined by flow cytometry will prove to be an accurate proxy for
      IgVH mutational status and this assay will be within the reach of any laboratory
      skilled in flow cytometry. The combination of ZAP-70 expression, CD38 antigen
      density, p53 function and the concentration of serum factors such as soluble
      CD23, is likely to provide extremely accurate prognostic information in future
      studies. This will assist in identifying Stage A patients who may benfit from
      early and/or more intensive treatment, as well as Stage B and C patients who may
      require alternative treatment strategies at the outset.

PMID- 15160908
TI  - Clinico-biological features and prognostic significance of PML/RARalpha isoforms
      in adult patients with acute promyelocytic leukemia treated with all trans
      retinoic acid (ATRA) and chemotherapy.
AB  - Debate exists over the clinical relevance of molecular heterogeneity of acute
      promyelocytic leukemia (APL). Based on the genomic breakpoint in PML gene, three
      different PML/RARalpha isoforms are recognized: intron 3 [short (S)], intron 6
      [long (L)] and exon 6 [variable (V)]. Studies on the prognostic significance of
      PML/RARalpha isoforms have reported contradictory results. This discrepancy may
      be related to differences in the treatment protocols, as some studies used ATRA
      alone during induction therapy. We analyzed the clinical course of 61 consecutive
      newly diagnosed patients with a genetically confirmed diagnosis of APL, treated
      with ATRA and chemotherapy at Princess Margaret Hospital from January 1994 to
      January 2002. The results of RT PCR at diagnosis were available on 48 patients.
      In this study, we report on clinico-biological features and prognostic
      significance of PML/RARalpha isoforms in these 48 patients. Of 48 patients,
      19(40%) had the S isoform and 29 (60%) had the L/V isoform. Median white blood
      cell (WBC) count for patients with S isoform was 8.6 [interquartile range Q1-Q3
      i.e. IQR 3.2-29] compared to 1.8 [IQR 1.0-4.9] for the L/V isoform group (P
      0.001). No difference was seen in number of patients achieving of molecular
      remission after induction and consolidation treatment in the two-isoform groups.
      The patients with S isoform had significantly inferior relapse-free survival
      (RFS) at 3 years compared to L/V isoform patients [48% (95% C.I. 19 77) vs. 92%
      (95% C.I. 82-100), P0.006]. In a univariate analysis, S isoform status (P 0.006)
      and high WBC count ( > or = 5 x 10(9)+/l) (P 0.017) were significant prognostic
      factors for RFS. No difference in overall survival was seen between the two
      isoform groups (P 0.35). Our results suggest that based on molecular
      characterization, it may be possible to identify a subgroup of APL patients at
      higher-risk of relapse.

PMID- 15160909
TI  - Molecular analysis of T-cell repertoire in patients with graft-versus-host
      disease after allogeneic stem cell transplantation.
AB  - Complementarity-determining region (CDR3) size spectratyping has often been used
      to analyze the clonal expansion of T-cells. CDR3 size spectratyping has been
      useful in the analysis of the oligoclonal expansion of T-cells in virus
      infection, graft-versus-leukemia effect (GVL), graft-versus-host disease (GVHD),
      and immune reconstitution of T-cells after allogeneic stem cell transplantation
      (allo-SCT). We analyzed 26 T cell receptor (TCR)-beta-chain subfamilies (VB) in
      25 patients who underwent allo-SCT. Fifteen of these patients developed acute
      GVHD (aGVHD). Many TCR-VB were skewed in the early stage. In these TCR-VB
      subfamilies, VB6 was most often skewed at the time of skin aGVHD. We then
      analyzed the average score of the complexity of 26 TCR-VB spectratypings in
      patients with or without cGVHD. The patients who developed chronic GVHD (cGVHD)
      had a lower average score of TCR-VB complexity than that of patients without
      cGVHD (P = 0.010). In particular. the patients who developed the quiescent type
      and de novo type of cGVHD from 4 months after allo- SCT had a lower average score
      of TCR-VB complexity at 3 months than that of the patients who had no cGVHD (P =
      0.0055). These results suggest that we might be able to consider a possible
      development of cGVHD by analyzing TCR-VB spectratyping after allo-SCT.

PMID- 15160910
TI  - Inter- and intra-observer reliability of Epstein-Barr virus detection in Hodgkin
      lymphoma using histochemical procedures.
AB  - EBER in situ hybridization (EBER) and LMP-1 immunohistochemistry (LMP-1) are
      widely used for identifying Epstein-Barr virus (EBV) within tumor cells of
      Hodgkin lymphoma (HL), but measurement error has never been formally evaluated.
      To determine assay reliability, 40 HL tumors with known EBV status were stained
      for both EBER and LMP-1 by two laboratories and reviewed twice by four
      hematopathologists. Inter- and intra-observer agreement were good to excellent,
      with kappas above 0.78 overall and above 0.60 for most subgroup analyses.
      However, reliability varied by histologic subtype, preparing laboratory, reviewer
      and EBV status determined on consensus review. For EBER, inter-observer agreement
      was high for nodular sclerosis HL but somewhat lower for EBV-negative mixed
      cellularity HL. For LMP-1, agreement was excellent for mixed cellularity HL but
      somewhat less reliable for EBV-positive nodular sclerosis HL. Agreement was good
      for EBER and LMP-1 applied to the same specimens but differed by consensus EBV
      status. The variability in assay interpretation justifies caution in comparing
      EBV association results across HL studies and underscores the need for
      interpretation guidelines.

PMID- 15160911
TI  - The interplay between c-Myc oncogene expression and circulating vascular
      endothelial growth factor (sVEGF), its antagonist receptor, soluble Flt-1 in
      diffuse large B cell lymphoma (DLBCL): relationship to patient outcome.
AB  - The c-Myc is a ubiquitous and multifunctional oncogene. Recently, data obtained
      from experimental study suggests the involvement of c-Myc oncogene in
      angiogenesis. In the present study the interrelation of sVEGF, sFlt-1
      concentrations and c-Myc oncoprotein expression at diagnosis were assessed in
      DLBCL and their impact on the patient outcome. Forty-five DLBCL patients beside
      10 normal controls were included. C-Myc oncoprotein was assessed by
      immunohistochemistry. SVEGF and sFlt-1 were determined by enzyme linked
      immunosorbent assay. C-Myc over-expression was detected in 66.6% of DLBCL. The
      DLBCL patient group with positive c-Myc over-expression showed significantly
      higher sVEGF and significantly decreased sFlt-1 as compared to group with
      negative c-Myc over-expression (P = 0.000 and P = 0.009 respectively). SVEGF was
      positively correlated to sLDH and s.beta2 microglobulin (r = 0.6, P = 0.000, r =
      0.69, P = 0.000) respectively. On the other hand sFlt-1 was negatively correlated
      to sLDH and s.beta2 microglobulin (r - 0.25, P > 0.05, r - 0.49, P = 0.001)
      respectively. The non-living DLBCL group showed significantly higher expression
      of c-Myc, higher concentration of sVEGF and lower concentration in sFlt-1 level
      as compared to the living group (P = 0.000 for all). Multivariate analysis
      revealed that c-Myc over-expression; high sVEGF and normal sFlt-1 levels at
      diagnosis had independent adverse influence on survival (relative risk: 17.9,
      35.7, 29.3, 2.63; P < 0.0001, P < 0.0001, and P = 0.03 respectively) IN
      CONCLUSION: C-Myc over-expression significantly associated with high sVEGF and
      normal sFlt-1 level in DLBCL patients, suggesting a complex interrelationship
      between c-Myc oncogene expression and angiogenic regulators. C-Myc over
      expression, high sVEGF and normal sFLt-1 levels at diagnosis had an independent
      adverse influence on survival in DLBCL patients and considered bad prognostic
      markers.

PMID- 15160912
TI  - Veterans with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
      have a markedly increased rate of second malignancy, which is the most common
      cause of death.
AB  - Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
      have an increased incidence of high-grade lymphoid malignancy. The risk of non
      lymphoid second malignancy in this population is not well-defined to date. To
      test the hypothesis that patients with CLL/SLL have an increased risk of second
      malignancy, we studied the rate of second malignancy in 132 CLL/SLL patients and
      compared it to the rate of malignancy (excluding non-melanomatous skin cancer) in
      the Central Arkansas Veterans Healthcare System population of approximately
      38,000 veterans over a period of 11.5 years. The rate of second malignancy,
      diagnosed concomitantly or after CLL/SLL, and the age-adjusted rate of malignancy
      calculated from tumor registry reports and demographic data, were used to
      calculate a Standardized Morbidity Ratio (SMR) with 95% confidence interval (CI).
      Twenty-one (16%) of the CLL/SLL patients had second malignancies (19 non
      lymphoid, 1 Richter's transformation and 1 Hodgkin's disease), which were fatal
      in 15 (71%) patients. The SMR for the CLL/SLL population was 2.97 (95% CI 1.84
      4.55) for second malignancy and 2.69 (95% CI 1.62-4.21) for non-lymphoid second
      malignancy. This study of a well-defined CLL/SLL population shows a significantly
      increased risk of second malignancy, which was the primary cause of death for 9%
      of all CLL/SLL patients (34% of all patient deaths).

PMID- 15160913
TI  - Detection of functional platelet-activating factor receptors on leukemic B cells
      of chronic lymphocytic leukemic patients.
AB  - Although platelet-activating factor receptors (PAF-R) are reported on normal B
      cells, few results are available concerning leukemic ones. We demonstrated
      functional PAF-R on cell and nuclear surfaces of leukemic B cells of chronic
      lymphocytic leukemic (CLL) patients. Analysis of 102 patients revealed dramatic
      differences for their membrane PAF-R expression, a result that might be related
      to their plasma IL-4 levels. In the light of the potent immunoregulatory role of
      PAF on B cell physiology, it is suggested that the presence or absence of PAF-R
      on leukemic B cells may profoundly affect their in vivo behavior.

PMID- 15160914
TI  - The spectrum of lymphoma with 8q24 aberrations: a clinical, pathological and
      cytogenetic study of 87 consecutive cases.
AB  - To define the histologic, cytogenetic (CG) and clinical spectrum of non-Hodgkin
      lymphoma (NHL) carrying an 8q24 (c-myc) translocation, 87 patients with an 8q24
      aberration were identified from 785 consecutive successfully analyzed cases.
      Aberrations involving 8q24 were found at diagnosis (n = 66) or at
      relapse/progression (n = 21). Histologically, Burkitt-like lymphoma (BLL) (32%)
      and Burkitt's leukemia/lymphoma (BL) (19%) with 8q24 changes at diagnosis, was
      the most common. Nevertheless, 46% of cytogenetically characterized BL and BLL
      cases do not show 8q24 aberrations. On the other hand, 8q24 aberration was also
      often found in follicular lymphoma (FL), mantle cell lymphoma (MCL) and low-grade
      NHL cases at progression. Cytogenetically, a de novo group is represented by
      classical t(8;14)(q24;q32) (n = 41), with isolated 8q24 changes, fewer secondary
      CG changes and represent mostly BL/BLL cases. In contrast, cases carrying variant
      8q24 aberrations (n = 29) contain more CG events, carried primary 14q32
      translocations, and included most FL, MCL and diffuse large B cell (DLBC)
      lymphoma cases. Clinically, the overall median follow-up was 8.6 months (range 0
      192), with a median survival of 4.2 months from CG analysis. The presence of a
      8q24 aberration give a statistically significant inferior prognosis than its
      absence in all histological groups, independent of clinical prognostic factors,
      when analyzed both at diagnosis and at relapse. We conclude that the finding of
      an 8q24 aberration is of marked negative prognostic significance, either at
      diagnosis or at disease progression, in a variety of NHL.

PMID- 15160915
TI  - Flow cytometry in the diagnosis of mediastinal tumors with emphasis on
      differentiating thymocytes from precursor T-lymphoblastic lymphoma/leukemia.
AB  - Flow cytometry (FC) has become the routine technique in the evaluation of
      hematopoietic neoplasms. Since the anterior mediastinum is a frequent site of
      involvement by both primary and secondary lymphoma/leukemia, flow cytometry plays
      an important role in the evaluation of mediastinal masses. The present study
      reviews 100 flow cytometry cases from patients presenting with mediastinal
      lesions. In 5 cases (5%) flow cytometry was not diagnostic due to either
      insufficient cell yield or low viability. In the remaining cases (95/100) cell
      suspensions were adequate for flow cytometry evaluation. Results showed that in
      31/32 (96.8%), 2/3 (66.7%), 7/9 (77.8%), 7/8 (87.5%) and 11/11 (100%) cases of B
      cell lymphoma, T-cell lymphoma, carcinoma, T-ALL/LBL and thymoma/thymic
      hyperplasia, respectively, the diagnosis could be reached by flow cytometry
      alone. Excluding HL, the general sensitivity of FC in diagnosing mediastinal
      tumors was approximately 92%. Among the 100 cases, flow cytometry gave non
      informative results in 3 cases of diffuse large B-cell lymphoma, 1 case of
      peripheral T-cell lymphoma, and 3 cases of carcinoma. No false positive results
      were encountered. The phenotypic pattern, especially surface CD3 expression
      versus forward scatter, reliably discriminated between immature thymocytes from
      thymoma/thymic hyperplasia from T-ALL/LBL. Flow methodology has the advantage of
      rapid turn-around time as well as high sensitivity, enabling patients with large
      anterior mediastinal masses and/or superior vena cava syndrome to begin treatment
      as promptly as possible. In experienced hands, flow cytometry plays a valuable
      and complementary role to histology and immunohistochemistry in diagnosing
      mediastinal tumors.

PMID- 15160916
TI  - Possible influence of clinical stage and type of treatment in the persistence of
      residual circulating t(14;18)-positive cells in follicular lymphoma patients.
AB  - Many patients with follicular lymphoma (FL) achieve response after treatment but
      complete remission (CR) rates are very low. Thus the majority of them will
      relapse, mainly those in advanced stage disease, due to the persistence of
      residual disease. Therefore, this study had the following aims: to determine the
      presence of bcl-2/IgH rearrangement in peripheral blood of early and advanced
      stage FL patients after treatment and to correlate it with their clinical
      situation at the same moment. We obtained 100 consecutive peripheral blood
      samples from 30 FL cases and conducted molecular studies using two separate semi
      nested PCRs for MBR and mcr rearrangements. These semi-nested PCRs for bcl-2/IgH
      rearrangement were able to detect one positive cell among 10,000 normal cells.
      Clinical and molecular evolution of patients diagnosed as early stage disease
      suggested that molecular response could be obtained even with conventional
      chemotherapy or radiotherapy. In this group of patients, 64% achieved molecular
      response in some point during follow-up. However, only 23% of patients diagnosed
      as advanced stage disease reached molecular response when treated with
      chemotherapy (with or without radiotherapy). Due to the low number of subjects
      assessed in this study, we only found a tendency to significance when clinical
      stage at the diagnosis was associated to molecular response (P = 0.095). We
      observed 100% of concordance between clinical remission and molecular response in
      patients after bone marrow transplantation or in those cases treated with
      monoclonal antibody anti-CD20. This retrospective study, performed in a
      restricted number of patients, suggests that molecular response can be obtained
      in FL patients diagnosed at early stage disease, even with conventional
      chemotherapy and radiotherapy. In advanced stage disease, concordance between
      clinical remission and molecular response was observed in the majority of
      patients after bone marrow transplantation or in those cases treated with
      monoclonal antibody anti-CD20. The prognostic significance of this data should be
      confirmed with extended follow-up and in a larger number of patients.

PMID- 15160917
TI  - Urinary albumin excretion is a predictor of response to treatment and disease
      progression in low-grade non-Hodgkin's lymphoma.
AB  - Slightly increased urinary albumin excretion (UAE) is frequently found in
      patients with malignant diseases and is associated with adverse prognostic
      factors. In the present study, the main objective was to elucidate the role of
      UAE as predictor of response to treatment and time to progression in low-grade
      non-Hodgkin's lymphoma. We included 52 patients with newly diagnosed follicular
      lymphoma grade 1 and 2. Pre- and post-treatment median UAE level was 17.5 and
      12.0 microg/min, respectively (P < 0.01). Significantly more patients with a pre
      treatment UAE below the median level were in CR after treatment (P < 0.05).
      Patients with a clinical response to treatment had a significantly lower
      frequency of UAE above the median post-treatment level (P < 0.05). UAE at the
      time of progression increased to a significantly higher level compared with the
      post-treatment level (26.5 vs. 16.0 microg/min; P < 0.0001). Median response
      duration and progression-free survival were significantly longer in patients with
      a post-treatment UAE below the median level (P < 0.001 and P < 0.0001,
      respectively). In conclusion, we found elevated UAE to be a highly sensitive
      indicator of clinical behavior in newly diagnosed low-grade lymphoma. Both
      response to treatment and time to progression were predicted by levels of UAE.
      Further studies are needed to confirm the clinical implications of UAE in
      lymphoma patients.

PMID- 15160918
TI  - Analysis of risk factors of the evolution of myelofibrosis in pre-fibrotic
      chronic idiopathic myelofibrosis: a retrospective study based on follow up
      biopsies of 70 patients by using the RECPAM method.
AB  - The advanced, fibrotic phase of chronic idiopathic myelofibrosis (CIMF) is
      preceded by a pre-fibrotic stage. However, the factors which may influence or
      predict the development of myelofibrosis are not well established. Thus we
      investigated follow up biopsies of 70 patients with CIMF, diagnosed in stages of
      no or only scant fiber increase, for the development of myelofibrosis. The
      influence of histopathological (megakaryocytes, initial fiber content), clinical
      (age, gender, splenomegaly, chemotherapy) and hematological (Hb, leukocyte- and
      platelet count) parameters on the development of myelofibrosis was evaluated by
      using the univariate Log Rank method and the multivariate recursive partition and
      amalgamation (RECPAM) analysis. Surveying a mean observation period of 47 months
      we found a development of significant myelofibrosis in 30 of the 70 patients. In
      the univariate analysis, the development of myelofibrosis was associated with
      increased megakaryocytes, initial fiber content and age of the patient. In the
      RECPAM analysis, the patients with a high megakaryocytic count and older age
      showed the highest risk of developing myelofibrosis (mean 58.3 and 60.1 months).
      The group with the best prognosis comprised the patients under 60 years which
      have a low content of megakaryocytes (mean 137 months). We found that the
      development of myelofibrosis in CIMF was best predicted by an increase of
      megakaryocytes within the bone marrow, possibly reflecting the release of growth
      factors by these cells. The next important risk factor was the age of the
      patients.

PMID- 15160919
TI  - Autoimmune myelofibrosis: report of three cases and review of the literature.
AB  - Autoimmune myelofibrosis is a distinct clinicopathological entity, recognizing
      immunopathogenetic mechanisms and occurring isolately or in association with
      systemic and/or organ-specific autoimmune diseases. It results in chronic
      cytopenias, and is defined by a pattern including bone marrow, peripheral blood,
      serological and clinical features. It has to be distinguished from other
      disorders having myelofibrosis. Among these, the most relevant differential
      diagnosis is with chronic idiopathic myelofibrosis, particularly when disclosing
      autoimmune clinical and/or laboratory features as epiphenomenon related to a
      secondary immune-dysregulation. Here we report on 3 patients admitted because of
      chronic cytopenias. In all of them, the clinicopathological evaluation
      essentially demonstrated myelofibrosis, not clustered megakaryocytes, reactive
      lymphoid infiltration in marrow biopsies, absence of significant tear-drop
      poikilocytosis and leukoerythroblastosis on peripheral blood smears, normal-sized
      spleen, positive autoimmune serology. The resulting patterns met the diagnosis of
      autoimmune myelofibrosis occurring isolately in a patient and associated with
      Sjogren's syndrome or concomitant Sjogren's syndrome and Hashimoto's thyroiditis
      in the other two, respectively. Transient improvements in cytopenias and
      unmodified myelofibrosis were observed following corticosteroid treatment. It is
      noteworthy the lack of a specific therapy, being the underlying pathophisiology
      of myelofibrosis still unclear. In conclusion, increased awareness of the
      clinicopathological pattern identifying autoimmune myelofibrosis is recommended
      in order to improve basic and clinical knowledge of this emerging entity.

PMID- 15160920
TI  - Expression of HOX genes in acute leukemia cell lines with and without MLL
      translocations.
AB  - In primary cells from acute leukemia patients, expression of the genes MEIS1,
      HOXA5, HOXA7 and HOXA9 has been reported to be correlated with the occurrence of
      MLL translocations. It was our aim to find out whether MLL mutant (MLLmu) and MLL
      wild-type (MLLwt) acute leukemia-derived cell lines might likewise be
      discriminated on the basis of HOX gene expression. Southern blot analysis,
      performed to verify the MLL status of the cells, showed that NOMO-1 was the only
      cell line not tested previously carrying a rearranged MLL gene. Fluorescence in
      situ hybridization analysis demonstrated that this cell line exhibited a
      reciprocal t(9;11)(q23;p22). Sequencing of RT-PCR products thereof identified
      unique MLL exon 10/AF-9 exon 5 fusion transcripts. We divided the acute leukemia
      derived cell lines (n = 37) according to the results of Southern blot analysis
      into MLLmu (n = 19) and MLLwt (n = 18). Expression of HOX genes was then analyzed
      by applying reverse transcriptase-polymerase chain reaction, Northern and Western
      blot analyses. Acute myeloid leukemia (AML) cell lines expressed the HOX genes
      significantly more often than acute lymphoblastic (ALL) cell lines. In ALL, cells
      with MLL translocations expressed the genes 4 times more often than MLLwt cells.
      Most distinct was the correlation between MLL status and MEIS1 expression in ALL
      derived cell lines: 8/8 MLLmu but 0/10 MLLwt cell lines expressed MEIS1. Northern
      and Western blot analysis confirmed that also HOXA9 and FLT3 were significantly
      more often and stronger expressed in MLLmu than in MLLwt ALL cell lines. These
      results suggest that MLL aberrations may regulate MEIS1 and HOXA9 gene expression
      in ALL-derived cell lines, while AML-derived cell lines express these genes
      independently of the MLL status.

PMID- 15160921
TI  - A novel ALL-L3 cell line, BALM-25, expressing both immunoglobulin light chains.
AB  - A human acute lymphoblastic leukemia (ALL)-derived cell line, BALM-25, was
      established from the bone marrow specimen of a 59-year-old male patient with B
      cell ALL L3 type (ALL-L3) at diagnosis. Immunophenotyping indicated mature B-cell
      characteristics including expression of cell surface and cytoplasmic
      immunoglobulin (Ig) chains, CD10, CD19, CD20, CD38, CD39, CD40, CD71, NU-B1 and
      HLA class II. T-cell and myeloid associated antigens tested were negative except
      CD5. BALM-25 cells have a morphological appearance typical for L3-type
      lymphoblasts. Regarding the expression of Ig chains, while the original leukemia
      cells expressed Ig lambda delta mu and hence a single light (L) chain isotype,
      the established line revealed double L chain expression both at the cell surface
      and the cytoplasmic level. Definitive double L chain expression was confirmed by
      flow cytometry and Western blot analysis. Southern blot analysis demonstrated
      rearrangement of the IgJH, the Ckappa and the Clambda genes. Cytogenetic analysis
      of BALM-25 revealed the following numerical and structural abnormalities: 55, X,
      add(X)(q12), + 2, add(3)(p21), + 5, add(7)(p13), add(11)(p11.2), add(11)(q?23),
      add(12)(p11.2), add(14)(q22), - 15, + 16, + 16,add(18)(11.2), + 20, + marl, +
      mar2, + mar3, + mar,inc. The established cell line, BALM-25, provides an
      unlimited supply of cell material for analyzing the unique (patho)physiology of
      Ig expression in general and for clarifying the pathogenesis of this type of B
      cell malignancy in particular.

PMID- 15160922
TI  - The effect of tetraethylenepentamine, a synthetic copper chelating polyamine, on
      expression of CD34 and CD38 antigens on normal and leukemic hematopoietic cells.
AB  - We have previously found that the synthetic polyamine tetraethylenepentamine
      (TEPA) significantly delayed differentiation and prolonged expansion of cord
      blood derived HPC in cytokine-supplemented cultures. Most HPC have the CD34+CD38+
      phenotype, but the minority CD34+38- cells are primitive subset of HPC that have
      the potential for long-term repopulation in vivo. We investigated the effect of
      TEPA on the CD34/CD38 surface antigen expression of human myeloid leukemia cell
      lines as well as normal cord blood derived hematopoietic cells. Confirming
      previous results, our data showed that both the leukemic and normal cells
      increased their CD38 expression when grown in serum-containing medium or when
      treated with retinoic acid. In the present study, we found that TEPA inhibited
      CD38 under these conditions in both normal and leukemic cells. As for CD34, TEPA
      increased the proportion of CD34 cells in short- and long-term normal cultures
      but not in the leukemic cell lines. These results suggest that ex vivo expansion
      of HPC depends on the presence of CD34+CD38- cells and that TEPA prolongs HPC
      expansion by inhibiting the CD38- to CD38+ transition.

PMID- 15160923
TI  - Use of iodine 131I-tositumomab radioimmunotherapy in a patient with Waldenstrom's
      macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia is an indolent B-cell malignancy that is
      characterized by high levels of IgM paraprotein production and is incurable with
      standard chemotherapy. Iodine 131I-Tositumomab (iodine-131-labeled murine anti
      CD20 monoclonal antibody; Bexxar) is a novel radioimmunotherapeutic agent that
      has a high response rate in relapsed or chemotherapy refractory, CD20-positive,
      low grade or transformed B-cell non-Hodgkin's lymphomas. There are no data on the
      use of radioimmunotherapy in Waldenstrom's macroglobulinemia. We report a patient
      with Waldenstrom's macroglobulinemia with transformation to a large B-cell
      lymphoma, who was treated successfully with iodine 131I-tositumomab. The patient
      had a complete response to the treatment, including disappearance of any
      detectable IgM paraprotein. This case report demonstrates the potential for
      radioimmunotherapy in CD20 positive B-cell malignancies.

PMID- 15160924
TI  - Atopic dermatitis-like non-erythrodermic leukemic variant of CD3(-/+dim) CD4(+)
      cutaneous T-cell lymphoma preceded by cutaneous papular xanthomatosis.
AB  - We report a patient with cutaneous papular xanthomatosis who 4 years later
      developed a CD3(-/+dim)/CD4(+) T-cell lymphoma. Pruritic xerotic non
      erythrodermic skin, eosinophilia and hyper-IgE were present and erroneously
      classified as atopic dermatitis. Flow cytometry and DNA ploidy analysis of both
      blood and skin lymphocytes, skin histology and blood T-cell receptor gene
      rearrangement studies confirmed diagnosis of T-cell lymphoma. Monoclonal CD3(
      /+dim)/CD4(+) T-cells were especially prone to the synthesis of IL-13, a cytokine
      that is involved in IgE-secretion, and comprised both a medium (diploid) and
      large (hyperploid) sized T-cell populations with a similar immunophenotype. The
      majority of the normal residual T-cells were large granular lymphocytes,
      expressed activation-related and natural-killer-associated markers and secreted
      high levels of interferon gamma, suggesting that they might correspond to active
      cytotoxic cells directed against the neoplastic T-lymphocytes.

PMID- 15160925
TI  - Acute basophilic leukemia with t(8;21).
AB  - Acute basophilic leukemia (ABL) is a rare form of leukemia. The diagnostic
      criteria have recently been described. Morphological evidence for basophilic
      lineage is required for its classification. However the criteria for remission
      status and standard therapy is not established. Here we have described an
      atypical case of ABL and reviewed the literature to high light issues regarding
      diagnosis and management, which need further discussion.

PMID- 15160926
TI  - Nodular lymphocyte predominant Hodgkin lymphoma in siblings.
AB  - Nodular lymphocyte predominant Hodgkin lymphoma is reported in 2 siblings with
      onset at the age of 47 in a woman of Indian ethnic origin and at the age of 52 in
      her younger brother. Although some cases of familial Hodgkin lymphoma can be
      related to inherited characteristics and others to Epstein-Barr virus infection,
      this is not so for familial nodular lymphocyte predominant Hodgkin lymphoma for
      which the aetiology and reason for the familial occurrence remain unknown.

PMID- 15160927
TI  - Chronic myeloid leukemia in an adolescent with Ollier's disease after intensive X
      ray exposure.
AB  - We report a 19-year-old man with Ollier's disease with multiple orthopedic
      procedures performed for leg length discrepancy; who developed chronic myeloid
      leukemia presenting with intramuscular hematoma. His symptoms resolved with
      cytoreductive treatment by hydroxyurea. Cytogenetic and molecular investigations
      showed a complex Philadelphia translocation t(9;22;13) (q34;q11.2;q12), with
      predominance of ela2 BCR/ABL splicing and deletion of reciprocal der(9) ABL/BCR
      locus, all suggesting poor prognosis. The cumulative X-ray exposure from repeated
      operations from the age of 7 to 12 years was estimated to be around 16 mSv,
      approximately the dose of 720 chest X rays. Literature review showed two other
      cases of leukemia occurring in patients with multiple enchondromatosis. Although
      the development of CML in this young patient might be related partly to genetic
      defects, the repeated radiation exposure, especially at young age and directly on
      the marrow tissue in the long bones, might also be an important pathogenetic
      factor.

PMID- 15160928
TI  - Cunninghamella bertholletiae infection (mucormycosis) in a patient with acute T
      cell lymphoblastic leukemia.
AB  - Cunninghamella spp. are unusual opportunistic pathogens that have been identified
      with increased frequency in immunocompromised patients. Clinical infection by
      this fungus is almost always devastating and usually fatal. Infections with this
      group of organisms have been seen most frequently in patients with hematological
      malignancy. Here we report the case of a patient with acute leukemia who
      developed multiorganic failure as a consequence of hematological dissemination by
      Cunninghamella bertholletiae. The case highlights the mortality associated with
      this fungal infection in immunocompromised patients, confirms the risk factors
      associated with non-candida fungal infections and shows a clinical presentation
      mimicking myocardial infarct and cerebrovascular stroke.

PMID- 15160929
TI  - Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): case
      report and review of the literature.
AB  - Acute myeloblastic leukemia cases carrying the translocation t(8;16) (p11;p13)
      are characterized by the M4 and M5 subtypes, erythrophagocytosis by the blast
      cells and a poor prognosis, suggesting a new clinical entity. The t(8;16) fuses
      the MOZ gene which encodes a histone acetyltransferase, located on 8p11 with the
      CBP gene which also encodes a histone acetyltransferase, located on 16p13, and
      recent reports suggested that the chimeric transcription MOZ-CBP is essential for
      leukemogenesis. A 68-year-old woman who had been treated mainly with paclitaxel
      and carboplatin for preceding ovarian cancer was admitted to our hospital,
      complaining of right breast mass. She was diagnosed as having breast cancer and
      acute monocytic leukemia (M5b). Cytogenetic study with spectral karyotyping
      analysis revealed the development of 47 XX, + 8, t(8;16)(p11;p13). Eleven cases
      of therapy-related t(8;16) leukemia including the present case have been
      reported, but prior treatment with paclitaxel and carboplatin-based chemotherapy
      has never been reported. The relation of histone acetylase and therapy-related
      leukemia is discussed.

PMID- 15160931
TI  - Vesicles as initial skin manifestation of disseminated fusariosis after non
      myeloablative stem cell transplantation.
AB  - A 52-year-old man underwent non-myeloablative stem cell transplantation from his
      HLA identical sister for the treatment of mantle cell lymphoma. On day 0, he
      developed a high-grade fever, watery diarrhea and vesicles scattered on the skin.
      Well experienced dermatologists diagnosed these lesions as VZV reactivation. High
      dose antiviral agents were ineffective, and Fusarium solani was cultured from his
      stool and sputum. Systemic fusariosis progressed rapidly and he died of
      multiorgan failure on day 18. It is sometimes difficult to differentiate between
      viral and fungal blisters based on macroscopic examinations. We recommend early
      histopathological examination of the skin, when HSCT recipients develop vesicles.

PMID- 15160930
TI  - Hepatitis B virus reactivation in a case of non-Hodgkin's lymphoma treated with
      chemotherapy and rituximab: necessity of prophylaxis for hepatitis B virus
      reactivation in rituximab therapy.
AB  - A patient with Non-Hodgkin's lymphoma is reported, in which reactivation of the
      hepatitis B virus was achieved from treatment with rituximab. The patient's HBs
      antigens were positive on admission, and she tested positive for HBs, HBe, and
      HBc antibodies, and negative for the HBe antigens. She was treated with a regimen
      of three courses of rituximab-containing anti-cancer drugs and one course of
      combined anti-cancer drugs. Throughout these chemotherapy courses, prednisolone
      was not given. After the fourth course of chemotherapy with the third rituximab
      she developed hepatic dysfunction, and the serum titers of HBs and HBc antibodies
      suddenly decreased. After administration of lamivudine, however, she gradually
      recovered from liver failure.

PMID- 15160932
TI  - Bone marrow transplantation in Jehovah's Witnesses.

PMID- 15160933
TI  - Prompt resolution of nasal aspergillosis with intranasal instillation of
      liposomal amphotericin-B (amBisome) and granulocyte transfusions.

PMID- 15160934
TI  - The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (APL) is an unique subtype of acute myeloid leukemia
      typically carrying a specific reciprocal chromosome translocation t(15;17)
      leading to the expression of a leukemia-generating fusion protein, PML-RARalpha.
      Nearly all de novo APL patients undergo disease remission when treated with all
      trans retinoic acid (ATRA) plus chemotherapy. APL patients that relapse following
      this type of therapy respond to As2O3 with disease remission once again. The
      mechanism of action of both ATRA and As2O3 appears to be by inducing granulocytic
      differentiation and this cellular differentiation seems to depend on PML-RARalpha
      proteolysis. ATRA treatment results in partial cleavage and complete degradation
      of PML-RARalpha protein in differentiation sensitive, but not in differentiation
      resistant APL cells. As2O3 treatment results in only complete degradation of PML
      RARalpha protein in both ATRA-sensitive and -resistant APL cells. PML-RARalpha
      appears to cause leukemia by acting as a transcriptional repressor of RARalpha
      target genes and by inhibiting activity of transcription factor C/EBPalpha.
      Therefore, PML-RARalpha proteolysis induced by ATRA and As2O3 may play an
      important role in overcoming the repressive activity of PML-RARalpha and allowing
      cellular differentiation to proceed. This review will focus on the status of the
      PML-RARalpha fusion protein and its relationship to gene and differentiation
      induction as well as differentiation resistance of APL cells.

PMID- 15160935
TI  - Breast cancer resistance protein (BCRP) in acute leukemia.
AB  - Multidrug resistance, cross-resistance to structurally and functionally unrelated
      drugs, is an important cause of treatment failure in acute leukemia. Multidrug
      resistance can result from the overexpression of ATP-dependent efflux pumps, such
      as P-glycoprotein and members of the multidrug resistance associated protein
      (MRP) family. Recently a novel transporter has been identified, which is called
      breast cancer resistance protein (BCRP), ABCG2 or mitoxantrone resistance
      protein. BCRP confers resistance to chemotherapeutic agents, such as
      mitoxantrone, doxorubicin and daunorubicin. This review describes BCRP detection
      techniques and the normal physiology of BCRP. The role of BCRP in the physiology
      of hematopoietic stem cells is addressed as well as the involvement of BCRP in
      multidrug resistance in acute leukemia. In AML and ALL, several studies showed
      that BCRP is expressed and functionally active at low, but variable levels.
      However, further studies are warranted to investigate its effect on clinical
      outcome, and explore whether patients could benefit from the combination of BCRP
      inhibitors and chemotherapy.

PMID- 15160936
TI  - Mechanisms of resistance to STI571 (Imatinib) in Philadelphia-chromosome positive
      acute lymphoblastic leukemia.
AB  - Resistance against STI571 (Imatinib) appears to be multifactorial, but the most
      likely mechanisms can be broadly categorized as interference with the
      pharmacologic activity of STI571 or genetic changes which alter the biologic
      behaviour of the leukemic cells. In Ph + ALL, responses to STI571 are not
      sustained, and in the overwhelming majority of patients development of resistance
      is rapid. Clinically, two types of resistance to STI571 can be distinguished:
      'primary resistance', corresponding to a failure to achieve fewer than 5% blasts
      in the bone marrow, and 'secondary resistance' in patients with STI571-induced
      complete remission who relapse despite continued STI571 treatment. Attempts to
      identify mechanisms by which Ph + ALL acquire resistance to STI571 have already
      been successful. Mutations in the ATP binding site of ABL are frequent events
      which counteract the antileukemic effect of STI571. Gene expression profiling has
      been shown to discriminate between resistant and sensitive leukemic cells.
      Application of this technique has also generated several hypotheses regarding the
      ability of leukemic cells to bypass the BCR-ABL signal transduction pathway. This
      may result in the proliferation of Ph + leukemic cells even in the presence of
      STI571.

PMID- 15160937
TI  - CD34+ CD90+ cells and late hematopoietic reconstitution after autologous
      peripheral blood stem cell transplantation.
AB  - Autologous peripheral blood stem cell transplantation (PBSCT) has been
      demonstrated to result in rapid. stable long-term engraftment. However, there has
      been considerable debate concerning the cells responsible for early and late
      hematopoietic reconstitution after PBSCT. Recently, CD34+ hematopoietic stem and
      progenitor cells have been clearly divided into two subpopulations by flow
      cytometry; namely undifferentiated pluripotent stem cells and differentiated
      committed progenitor cells. However, only a few studies have defined which subset
      contained in graft products might be the most predictive for late hematopoietic
      reconstitution after PBSCT. In this review, we present updated information
      regarding the relationships between the number of infused CD34+ cells or their
      immature subsets such as CD34+ CD90+ cells and the late hematopoietic
      reconstitution after PBSCT, and discuss the threshold dose of CD34 + CD90+ cells
      required for sustained long-term engraftment.

PMID- 15160938
TI  - Update in the epidemiology, prophylaxis, and treatment of fungal infections in
      patients with hematologic disorders.
AB  - Invasive fungal infections contribute to the morbidity and mortality of
      immunosuppressed patients treated for hematologic malignancy and those undergoing
      hematopoietic cell transplantation. After years of limited advances, the
      management of fungal infections in these patients is now rapidly evolving. In
      this update, we will outline changes in the epidemiology of invasive fungal
      infections, discuss current issues in diagnosis and susceptibility testing, and
      review the current classes of antifungal drugs, focusing on newly licensed
      therapies. Data on antifungal prophylaxis, empiric therapy, and treatment of
      documented invasive fungal infections including single agents and combinations
      with newly licensed agents will be reviewed with emphasis on their impact on
      patients with hematologic malignancies.

PMID- 15160939
TI  - Acute panmyelosis with myelofibrosis.
AB  - Acute panmyelosis with myelofibrosis (APMF) is an ill-defined disorder that may
      either evolve as a clonal hematopoietic condition or as a sequel of toxic
      exposure to the bone marrow (BM). Therefore, controversy and discussion continues
      as to whether APMF may be considered as a hyperfibrotic (de novo) myelodysplastic
      syndrome (MDS), as acute myeloid leukemia (AML) or as a severe toxic myelopathy
      with accompanying myelofibrosis. In this context scant knowledge exists about BM
      findings, but especially evolution of this disorder according to sequential
      examinations. Clinically patients present with pancytopenia, a very few blasts in
      the peripheral blood and no or little splenomegaly. Initially BM histopathology
      is characterized by different degrees of reticulin-collagen fibrosis and wide
      ranges of cellularity with a prominent left-shifted and often macrocytic
      erythropoiesis associated with a reduction and maturation defects of the
      neutrophil series. Most conspicuous are abnormalities of the megakaryocytes
      including loose clustering, dislocation towards the endosteal border and
      appearance of atypical microforms with compact nuclei. Moreover, besides
      myelofibrosis in a number of patients the interstitial compartment displays a
      remarkable inflammatory reaction with lymphoid nodules, abundant iron-laden
      macrophages, perivascular plasmacytosis and increase in microvessels. Repeatedly
      performed BM biopsies reveal an accumulation of dispersed or clustered CD34+ and
      lysozyme-expressing blasts in keeping with the insidious transformation into
      acute leukemia. Prognosis is unfavorable with a median survival of less than 1
      year. In conclusion, APMF has to be regarded as a condition that shows
      considerable overlappings with primary hyperfibrotic MDS, AML and toxic
      myelopathy (secondary MDS) with accompanying myelofibrosis and therefore can not
      be considered as a definite clinical entity.

PMID- 15160940
TI  - Derivative chromosome 9 deletions in chronic myeloid leukemia are associated with
      loss of tumor suppressor genes.
AB  - It has recently been postulated that the absence of a single tumor suppressor
      gene (TSG) allele can provide a selective advantage for an emerging tumor cell.
      We have characterized the precise extension of the deletion on der(9) in 20
      chronic myeloid leukemia (CML) cases using FISH analysis with an appropriate set
      of BAC/PAC probes to attempt a better definition of TSGs encompassed by these
      genomic deletions. Chromosome 9 deletions on the der(9) were detected in 15 (75%)
      cases; the TSG PTGES gene was lost in 11 (73%) cases. Chromosome 22 deletions on
      der(9) were found in 18 (90%) of the analysed cases; two TSGs were found located
      inside the deleted sequences of chromosome 22: SMARCB1 and GSTT1. These TSGs were
      found deleted in 16 (89%) cases bearing deletions of chromosome 22. Fourteen
      (70%) patients were treated with IFN-alpha therapy: 12 did not obtain complete
      haematologic remission (CHR) and 2 were not evaluable for response. Therefore,
      the patients did not respond to the IFN-alpha treatment started Glivec obtaining
      CHR and major cytogenetic response (MCR). The observation that deletions on
      der(9) are associated with the loss of TSGs suggests their possible involvement
      in the CML outcome, mediated by a haplo-insufficiency mechanism.

PMID- 15160942
TI  - Phase I/II clinical study of topotecan and cytarabine in patients with
      myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid
      leukemia.
AB  - Topotecan, a topoisomerase-I inhibitor is an active drug in the treatment of AML
      and MDS. To evaluate its toxicity and efficacy in a combination regimen with
      cytarabine, we conducted a clinical phase I/II trial in patients with relapsed
      acute myeloid leukemia (AML) or relapsed or newly diagnosed MDS RAEB, RAEB-t or
      CMML. Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were
      treated with 1.25 mg/m2 topotecan as continuous intravenous infusion daily for 5
      days and cytarabine 1.0 g/m2 by infusion over 2 h daily for 5 days (TA). Cycles
      were repeated on day 28. The median observation time was 131 weeks (range: 36-196
      weeks). A total of 37 cycles of TA were administered. In 1 patient, the dose of
      TA had to be reduced and in 1 patient, there was a treatment delay for the second
      cycle, both because of hematologic toxicity. The most frequent non-hematologic
      side-effect of TA was fever, which occurred in 17 patients (89%) with
      temperatures over 38 degrees C. None of the patients died due to any treatment
      related toxicities, but 2 patients (10%) died within 1 month due to disease
      progression. A CR was achieved in 7 patients (33%), 3 of whom were MDS and 4 AML.
      A partial remission was reported in 8 patients (38%), no change of disease in 2
      patients (10%) and progressive disease in 4 patients (19%). The median remission
      duration was 18 weeks (range 2-161 weeks) for MDS patients and 11 weeks (range 2
      49 weeks) for AML patients. The time to progression for patients of 60 years and
      older (n = 10) was 16 weeks (range 2-49 weeks) and the survival was 32 weeks
      (range 2-119 weeks). TA is a feasible and efficacious chemotherapeutic
      combination for the treatment of MDS RAEB, RAEB-t, CMML and AML. For patients of
      60 years and older, this regimen is also a safe option.

PMID- 15160941
TI  - Central nervous system failure in patients with chronic myelogenous leukemia
      lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic
      leukemia treated with imatinib (STI-571).
AB  - Isolated central nervous system (CNS) relapse occurred in 5 out of 24 patients
      (20.8%) with chronic myeloid leukemia (CML) lymphoid blast crisis (2),
      Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) (2) or
      CML with biphenotypic markers (1) treated on imatinib mesylate (IM) protocols at
      our institution. CNS relapse occurred despite peripheral blood (5) and bone
      marrow (3) complete responses. Median time to CNS relapse was day 32 (range 23 to
      100). This observation raised the possibility that IM may not penetrate into the
      CNS. Simultaneous plasma and cerebral spinal fluid (CSF) IM levels were
      determined in four subsequent patients by liquid chromatography and mass
      spectrophotometric assay. Levels of IM were found to be approximately two logs
      lower in CSF than in plasma (0.044 microg/ml (0.088 +/- 0.029 micrro) vs 3.27
      microg/ml (6.54 +/- 0.93 microM)). CSF levels were substantially below the
      concentration required for inhibition of BCR-ABL and killing of cell lines in
      vitro. These results suggest that IM may not penetrate the intact blood/brain
      barrier and its implications are discussed.

PMID- 15160943
TI  - Leukaemic subtype of marginal zone lymphoma: a presentation of three cases and
      literature review.
AB  - The recent World Health Organization (WHO) classification recognizes three
      subtypes of marginal zone lymphoma (MZL): extranodal MZL of mucosa-associated
      lymphoid tissue (MALT), splenic MZL and nodal MZL. As a group, MZL share
      morphological and immunophenotypic features similar to that of the marginal zone
      B-cell in secondary B-follicles, the postulated common cell of origin. There is,
      however, increasing information about molecular heterogeneity between the types
      of MZL, suggesting different aetiology and highlighting our current incomplete
      understanding of this evolving entity. We describe the presentation and clinical
      course of three patients with MZL who do not fit the currently recognized WHO
      categories, and best fit the putative category of MZL, leukaemic subtype. We
      review the current literature on this newly described entity, highlighting the
      importance of its recognition.

PMID- 15160945
TI  - Adult T-cell leukemia/lymphoma (ATLL): report of two fully documented Hellenic
      patients.
AB  - ATLL is etiologically associated with HTLV-I retrovirus. A population of 10 to 20
      million worldwide is estimated to be infected by the virus, but only 1-4% develop
      ATLL during a 70-year lifespan. The latency period is more than 30 years. The aim
      of this study was to report two cases of ATLL in Greek patients with the
      concomitant study of their family members. A 55-year-old woman and a 59-year-old
      man presented with leucocytosis and lymphocytosis. Both were asymptomatic and
      physical examination was unremarkable except for minimal lymphadenopathy in the
      second patient. In both patients blood smears showed small-to-medium-sized,
      multilobulated lymphocytes, with different degrees of nuclear irregularity.
      Immunophenotypic study was as follows: CD2 + (97%), CD3 + (95%), CD5 + (95%),
      CD3/CD4 + (93%), CD3/CD25 + (84%), CD7 -/CD4 + (89%) CD2 + /HLA-DR + (53%),
      TCRabeta + (96%) and CD7-(7%). Bone marrow biopsy revealed a normal cellularity
      with dyserythropoiesis and scattered small lymphocytes (CD4 + on immunostaining)
      Serum HTLV I and II antibodies were positive. T-cell receptor gamma-chain
      rearrangement was positive in blood lymphocytes by PCR. Cytogenetic analysis
      showed complex karyotypic abnormalities. DNA analysis by PCR demonstrated the
      integration of the HTLV-I DNA in the DNA of the neoplastic T cells. Both patients
      rapidly developed acute type ATLL. In the first patient multiple subcutaneous
      nodules on the palmar surface of both hands were also observed. She received
      deoxycoformycin, which was stopped because of autoimmune hemolytic anemia.
      Corticosteroid treatment was initiated, with gradual improvement. She suffered
      from recurrent opportunistic infections. She is currently under interferon and
      zidovudine therapy with stable blood parameters. Chemotherapy was administered to
      the other patient with > 50% initial response. Both patients' families were
      tested for serum anti HTLV-I antibodies and their mates were found to be
      positive; they also had detectable viral DNA by PCR analysis while asymptomatic,
      with no abnormal clinical findings and normal white blood cell count and
      morphology. In conclusion, the two aforementioned patients are the first fully
      documented ATLL patients described in Greece. Investigation for HTLV-I antibodies
      should be mandatory in all patients with T-cell lymphoproliferative disorders.

PMID- 15160944
TI  - Maintenance therapy with a monthly injection of alemtuzumab prolongs response
      duration in patients with refractory B-cell chronic lymphocytic leukemia/small
      lymphocytic lymphoma (B-CLL/SLL).
AB  - Alemtuzumab, the monoclonal anti-CD52 antibody, has clinical activity in B-cell
      and T-cell malignancies at the dose of 30 mg three times weekly for 9-12 weeks.
      This standard regimen induced responses usually shorter than 6 months. To prolong
      time to progression, we initialized a phase II study with an identical initial
      scheme until partial response, followed by a maintenance therapy lasting at least
      4 months. Eleven heavily pretreated patients (8 with B-chronic lymhocytic
      leukemia (B-CLL) and 3 with small lymphoctyic lymphoma (SLL)) have been treated
      with this maintenance regimen (MR patients) and were retrospectively compared to
      5 patients (3 B-CLL and 2 SLL) treated with the standard regimen (SR patients).
      Patients characteristics before treatment were identical in both groups.
      Objective response was reached by 9 (82%) MR patients and 3 (60%) SR patients (p
      NS). After the treatment, 8 (73%) MR patients and all SR patients progressed with
      a median time at 12.2 months and 3 months respectively. Survival time from
      alemtuzumab was significatively different (P < 0.005). None of the patients died
      in the MR group with a median follow-up at 16 months. In the SR group, the median
      survival from alemtuzumab was 5.9 months. We did not observe any differences in
      terms of hematological toxicites and infections between the two groups. In
      conclusion, maintenance alemtuzumab therapy seems to increase the time to
      progression and the survival, without adding hematological toxicities and
      infectious complications. More patients are needed to confirm this observation.

PMID- 15160946
TI  - Splenic mastocytosis: report of two cases and detection of the transforming
      somatic C-KIT mutation D816V.
AB  - In the vast majority of patients with systemic mastocytosis (SM), the bone marrow
      is the primary extracutaneous site of disease. In addition to bone marrow
      involvement, other visceral organs such as the spleen, liver or the
      gastrointestinal tract, may also be affected. However, isolated involvement of a
      single extramedullary organ is rarely seen in SM. We report on two patients with
      SM with splenic involvement, lack of 'diagnostic' mast cell (MC) infiltrates in
      the bone marrow, and absence of skin lesions. In one patient, a myelodysplastic
      syndrome was diagnosed prior to the detection of SM. Both patients presented with
      massive splenomegaly and multifocal MC infiltrates in splenic tissues. These MCs
      also expressed CD25 as well as the C-KIT mutation D816V. In consecutive
      examinations, the mutation was also detected in the bone marrow in both patients
      suggesting diffuse infiltration with neoplastic cells. In summary, our data show
      that the spleen can be a primary site of disease in rare cases of SM.
      Mastocytosis should therefore be considered as a (rare) differential diagnosis in
      patients with splenomegaly of unknown etiology.

PMID- 15160947
TI  - Anti-leukemic and anti-GVHD effects of campath-1H in acute lymphoblastic leukemia
      relapsed after stem-cell transplantation.
AB  - Despite aggressive approaches, including second transplant, donor lymphocyte
      infusion and several new agents, the prognosis of acute lymphoid leukemia (ALL)
      patients relapsing after stem-cell transplantation (SCT) remains poor. Monoclonal
      antibodies (moAb) could provide a useful tool in this setting. In particular,
      anti-CD52 moAb is useful in lymphoid malignancies. We thus treated as
      compassionate with campath-1H 3 ALL patients relapsed after SCT. In 2 cases we
      observed a reduction of peripheral blood and/or bone marrow blasts. In 1 case a
      GVHD grade reduction was observed. Larger trials are required in order to define
      the role of campath-1H in ALL.

PMID- 15160948
TI  - Possible multiple myeloma dedifferentiation following thalidomide therapy: a
      report of four cases.
AB  - Thalidomide has been shown to be effective in approximately 30% of patients with
      refractory or advanced multiple myeloma (MM). Here we report on 4 cases of
      patients treated with thalidomide for refractory MM showing dedifferentiation of
      the neoplasm. In these cases thalidomide treatment despite reduction of M
      component-was followed by disease progression and a very poor clinical outcome
      which was paralleled by bone marrow plasmacytosis showing marked signs of
      dedifferentiation, inducing us to speculate on a potential role of thalidomide on
      dedifferentiation of myeloma cells. In our opinion, a possible dedifferentiation
      of MM should therefore be taken into account in MM patients treated with
      thalidomide when clinical course deteriorates despite reduction of M-component.

PMID- 15160949
TI  - Acute leukemia with natural killer cells antigens in Brazilian children.
AB  - Malignancies arising from Natural Killer cells (NK) were described mainly
      comprising disorders related to large granular lymphocyte expansion. Clinical,
      morphological and immunophenotypic characteristics of myeloid/NK cell precursor
      acute leukemia (M/NK-AL) have been mainly described in adult patients. We
      identified nine children with M/NK-AL precursor cells in a series of 264
      childhood acute leukemia diagnosed in our laboratory from consecutive referrals
      before treatment. CD34 +/-, CD13/33 +, CD11b +, a-MPO + and CD56 +, characterized
      these cases with TcR alphabeta and gammadelta negative cells. The differential
      diagnosis between subtypes of NK leukemia with those of lymphoid or myeloid
      origin in childhood raises the question regarding the pathogenesis and
      therapeutic implications of this rare entity in children.

PMID- 15160950
TI  - Comparison of bone marrow aspirates and biopsies in pediatric patients with ALL
      at days 7 and 14 of induction therapy.
AB  - The percentage of blasts in the bone marrow aspirates at day 7 or 14 of induction
      therapy in pediatric ALL patients is an indicator of rapid early response and an
      independent prognostic factor for long term outcome. Discrepancies between the
      percentages of blasts in bone marrow aspirates compared to biopsies have been
      reported. In a retrospective study on 44 consecutive patients diagnosed with ALL
      between 1998 and 2001, important differences were observed in the percentage of
      blasts between bone marrow aspirates and biopsies at days 7 and 14 of induction
      therapy.

PMID- 15160951
TI  - Treatment of multiple myeloma with all-trans retinoic acid alone and in
      combination with chemotherapy: a phase I/II trial.
AB  - All-trans retinoic acid (ATRA) is a derivative of vitamin A. ATRA inhibits the
      growth of human myeloma cell lines and freshly isolated myeloma cells in vitro
      mainly by down-regulating interleukin-6 receptor. Clinically, however, ATRA alone
      has not been efficacious and adverse events, notably hypercalcemia, have been
      common. In the present study 10 patients with stable multiple myeloma after
      conventional chemotherapy received ATRA alone for 2 months, followed by a
      combination of ATRA and the chemotherapy regimen during which no further
      reduction of the paraprotein had occurred. The purpose of the combination therapy
      was to sensitize the myeloma cells with ATRA to chemotherapy by blocking the
      growth-promoting effect of IL-6. Although ATRA was well tolerated, ATRA alone
      lacked clinical efficacy. The combination therapy resulted minimal responses in 4
      patients and relatively long progression-free survival in 4 patients was
      achieved. In 3 of these responding patients serum concentrations of interleukin-6
      and/or soluble interleukin-6 receptor were elevated prior to the study. The bone
      marrow cells of responding patients were sensitive to ATRA in vitro. These
      results show that ATRA alone is not effective to treat multiple myeloma. There
      may be some beneficial effect of ATRA in combination chemotherapy in selected
      patients who have activated IL-6 signaling.

PMID- 15160952
TI  - High-dose topotecan, melphalan and cyclophosphamide (TMC) with stem cell support:
      a new regimen for the treatment of multiple myeloma.
AB  - The goal of this trial was to assess the toxicity and potential efficacy of high
      dose topotecan, melphalan and cyclophosphamide as a preparative regimen for
      patients with multiple myeloma undergoing autologous stem cell transplantation.
      Eighteen patients were treated, 8 for first remission consolidation, 4 with
      relapse sensitive disease, 3 primary refractory and 3 relapsed refractory. The
      median age was 56 (38 - 65) and the median number of prior regimens was 3 (1 -
      8). Patients received cyclophosphamide 1 g/m2/d on days -6, -5, -4; melphalan 70
      mg/m2 on days -3, -2 and topotecan 3.0 to 3.5 mg/m2/d on days -6 to -2.
      Peripheral blood stem cells were infused on day 0. Toxicity (Bearman Toxicity
      Criteria) was mostly limited to grade 1 - 2 mucositis and grade 1 diarrhea. There
      were no transplant-related deaths. The overall response rate at 3 months post
      transplantation was 89% with 17% CR, 2 of those in refractory patients. The
      overall response rate in refractory patients was 67%. With a median follow up of
      12.3 months, 89% of patients are alive. The TMC regimen is well tolerated and
      produces high response rates. Further evaluation of TMC to fully assess response
      and survival is ongoing.

PMID- 15160953
TI  - Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas:
      preserved efficacy with decreased toxicity.
AB  - Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require
      specialized therapy. Although intensive, multi-agent regimens have been effective
      in children, results are more variable in adults. Magrath et al. previously
      described a regimen that was highly effective in children and young adults. This
      phase II study of a modified Magrath regimen was designed to assess its efficacy
      in older adults and reduce treatment-related toxicity. Fourteen patients with
      Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two
      categories: low-risk (normal LDH and a single focus of disease measuring less
      than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients
      received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin,
      adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by
      high-dose systemic methotrexate, regimen A). High-risk patients received four
      alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of
      ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The
      modified treatment regimen was associated with no grade 3/4 neuropathy and only
      one episode of grade 3/4 mucositis. All patients completed protocol therapy and
      there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%)
      achieved a complete response; 1 patient achieved a PR and 1 patient died of
      progressive disease. Nine patients (64%) are alive and disease free at a median
      follow-up of 29 months. This modified Magrath regimen is effective and well
      tolerated in a representative group of older adult patients.

PMID- 15160954
TI  - Isolated bone marrow involvement in diffuse large B cell lymphoma: a report of
      three cases with review of morphological, immunophenotypic and cytogenetic
      findings.
AB  - Diffuse large B cell lymphoma (DLBL) comprises a heterogenous entity
      characterized by the presence of large cells, exhibiting a mature B cell
      phenotype. The high proliferation rate and aggressive disease remain a
      therapeutic challenge, but the apparent biological diversity permits a risk
      stratification model for prognostic grouping through the International Prognostic
      Index (IPI). Empirical to this approach is the consideration of cytogenetic data,
      offering an insight into the pathogenetic events which may underlie neoplastic
      clonal evolution and disease progression. We describe three cases of DLBL
      presenting with isolated marrow disease, a rare primary finding in this lymphoma.
      All three cases showed involvement of blood and bone marrow without evidence of
      splenic or lymph node involvement on imaging studies. Histological and
      immunophenotypic findings were similar in all three cases, outlining the
      phenotypic maturity of this disease. Cytogenetic analysis revealed complex
      karyotypes in the two cases examined. M-FISH (multicolour fluorescent in situ
      hybridization) performed on bone marrow from case 1 showed several cryptic
      translocations not evident on G-banding, including a novel translocation between
      2p and 9p, and an unbalanced translocation between 14q and 11q. Cytogenetic
      analysis in case 2 showed abnormalities involving 7q, 9p at the site of the INK4a
      gene, and the bcl-2 locus, findings confirmed by M-FISH. These cases serve to
      highlight the biological and cytogenetic heterogenity of DLBL and emphasize the
      need for complementary investigations in the characterization of this entity.

PMID- 15160955
TI  - Successful treatment of systemic and central nervous system lymphomatoid
      granulomatosis with rituximab.
AB  - Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder with a
      mortality rate approaching 60% in the first year. The median survival is 14
      months from the time of diagnosis. Although a variety of chemotherapeutic
      regimens have been utilized, there is no standard treatment. Studies have shown
      that in most cases the malignant cells are B-cells, which induce massive
      infiltration of reactive T-lymphocytes in the background. The disease is
      therefore considered as a T-cell rich B-cell lymphoproliferative disorder. We
      report a case of LYG with pulmonary, hepatic, central and peripheral nervous
      system involvement that was successfully treated with the anti-CD20 (B-cell)
      monoclonal antibody, Rituximab.

PMID- 15160956
TI  - Primary cardiac lymphoma: report of two cases occurring in immunocompetent
      subjects.
AB  - Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at
      presentation, are rare events. They are frequently recognized at autopsy and
      generally carry a poor prognosis due either to a delay in the diagnosis or to
      infiltration of heart structures. We report here on two patients with large B
      cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors
      infiltrating mainly the right atrium and the inter-atrial septum. Diagnosis was
      established by ultrasound-assisted transesophageal biopsy of the intra-atrial
      multilobated tumor mass. He was treated with Rituximab-implemented high-dose
      sequential (R-HDS) chemotherapy followed by autologous peripheral blood stem cell
      transplantation, attaining complete response. He had no evidence of disease 24
      months from onset. The second patient was a 70-year-old woman who presented with
      pericardial tamponade and low-output cardiac failure. Despite prompt
      pericadiocentesis and chemotherapy with cyclophosphamide and vincristine, she
      died 2 weeks later. Postmortem examination revealed large B-cell lymphoma
      proliferation confined to the heart. Whether primitive heart localizations
      represent an independent prognostic factor, and what specific measures should be
      adopted in patients with this rare presentation is the subject of the present
      report and review of the literature.

PMID- 15160957
TI  - Adrenal involvement in non-Hodgkin's lymphoma: four cases and review of
      literature.
AB  - Primary adrenal non-Hodgkin's lymphoma is very rare. We have seen 2 such cases
      among 241 cases of non-Hodgkin's lymphoma (0.83%) over the past 4 years. We could
      detect 2 more cases who had adrenal involvement, in addition to other extra nodal
      disease sites. Review of English literature revealed 65 cases of primary adrenal
      non-Hodgkin's lymphoma, most being single case reports. Salient features included
      median age of 68 years (mean age of 47.25 years in our series), bilateral adrenal
      involvement in 60%, and predominantly diffuse large cell histology with 'B' cell
      immunophenotype. Adrenal insufficiency was present in two-thirds of the patients
      at diagnosis. Chemotherapy with or without radiotherapy is the mainstay of
      treatment. About half the patients respond to treatment, with median survival of
      4 months. The high index of suspicion for early diagnosis and prompt treatment
      may improve outcome.

PMID- 15160958
TI  - Enhanced cytotoxicity of rituximab following genetic and biochemical disruption
      of glycosylphosphatidylinositol anchored proteins.
AB  - Rituximab, an anti-CD20 monoclonal antibody used to treat B cell
      lymphoproliferative disorders and autoimmune diseases, kills cells through
      complement dependent cytotoxicity, antibody-dependent cellular toxicity and
      apoptosis. A mechanism of resistance to rituximab is upregulation of the
      complement regulatory proteins, CD59 and CD55. Paroxysmal nocturnal
      hemoglobinuria (PNH) is a hematopoietic disorder caused by PIGA mutations that
      lead to a loss of all glycosylphospatidylinositol (GPI)-anchored proteins
      including, CD55 and CD59. We compared the cytotoxic activity of rituximab against
      a PNH B cell line, LD -, and the isogenic cell line LD - PIGA + in which GPI
      anchor expression was restored by stable transfection of PIGA. The PNH cell line
      was more sensitive to rituximab-mediated killing than the LD - PIGA + cells.
      Biochemical disruption of GPI anchors with phosphatidylinositol specific
      phospholipase C (PIPLC), a phospholipase that cleaves GPI-anchored proteins, also
      increased rituximab-mediated killing. Thus, genetic and biochemical interruption
      of GPI anchor proteins augments sensitivity to rituximab.

PMID- 15160959
TI  - Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma.
AB  - An association between mastocytosis and monoclonal gammopathy is a relatively
      rare but well recognized clinical finding. In the majority of cases, however,
      overt myeloma or lymphoma is not detectable morphologically. Here we describe the
      case of a 51 year-old male patient first presenting with paresis of the right
      facial nerve and the serological finding of IgM kappa paraproteinemia. The
      patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa
      type skin lesions. Histological examination of a trephine biopsy specimen
      revealed the unusual coexistence of plasma cell myeloma and mastocytosis.
      Immunohistochemically, plasma cells were found to exhibit a monotypic staining
      for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic
      nature. Mast cells showed prominent spindling and formed dense multifocal
      infiltrates, thus enabling the diagnosis of bone marrow mastocytosis.
      Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117).
      In addition, aberrant expression of CD25 on mast cells was detected, confirming
      the coexistence of a neoplastic mast cell-proliferative disorder. According to
      the WHO proposal for classification of hematopoietic malignancies, this unique
      case, showing the association of two very rare haematologic neoplasms, can
      therefore best be referred to as bone marrow mastocytosis associated with IgM
      kappa plasma cell myeloma (SM-AHNMD).

PMID- 15160960
TI  - Hyperthyroidism six years post-BMT for acute myeloblastic leukemia in a patient
      on long-term lithium therapy for bipolar affective disorder.
AB  - Lithium is commonly used to treat bipolar affective disorder. It is well known to
      adversely affect thyroid function, most commonly causing hypothyroidism.
      Hyperthyroidism is a rare complication. Similarly, total body irradiation (TBI)
      associated with BMT is well known to affect thyroid function frequently causing
      hypothyroidism. Hyperthyroidism secondary to TBI is unusual. To have both a
      history of chronic lithium therapy and TBI with a BMT in patient presenting with
      hyperthyroidism is an extremely atypical situation. We describe a 39-year-old
      male who presented with primary hyperthyroidism after 18 years of lithium use for
      bipolar affective disorder and 6 years post-BMT for AML-M4.

PMID- 15160961
TI  - Cyclic lymphocytic vasculitis associated with chronic lymphocytic leukemia.
AB  - Lymphocytic cutaneous vasculitis associated with a haematological malignancy has
      rarely been reported. Here, we describe a 61 year-old woman with chronic
      lymphocytic leukemia (CLL) who presented with cutaneous lesions on both hands.
      These lesions improved after all combination chemotherapy courses and recurred
      before each course. Repetitive skin biopsies revealed lymphocytic vasculitis.
      After 7 courses of chemotherapy, she had a complete remission. Skin lesions
      disappeared and did not recur. The cyclic pattern of lymphocytic vasculitis and
      its relation with CLL disease activity are interesting clinical features in this
      case.

PMID- 15160962
TI  - Agnogenic myeloid metaplasia with pleural extramedullary leukemic transformation.
AB  - Agnogenic myeloid metaplasia (AMM) is one of the myeloproliferative disorders,
      and is usually accompanied by extramedullary hematopoiesis (EMH) in various
      organs, mainly in the liver, spleen and lymph nodes. Extramedullary hematopoiesis
      and/or leukemic transformation of EMH in the pleura is a rare occurrence and is
      usually asymptomatic. Pleural involvement is usually diagnosed on postmortem
      examination. Herein we describe a 71-year-old man with newly diagnosed agnogenic
      myeloid metaplasia who was evaluated for progressively worsening dyspnea,
      pulmonary hypertension and bilateral pleural effusions. EMH involving the lungs
      and pleura was suspected. A sulfur colloid technetium 99m bone marrow scan
      performed to detect extramedullary hematopoiesis was negative. The diagnostic
      thoracentesis yielded bloody fluid that contained a large population of
      myeloblasts, indicating pleural leukemic transformation. The patient received 100
      cGy to the whole lung for treatment of pulmonary hypertension due to EMH. This
      was followed by 1500 cGy total dose of radiation to the left lung for pleural
      extramedullary leukemic transformation. Pleural effusions resolved and repeat
      echocardiography showed reduction of the pulmonary artery pressure. Three months
      later he had leukemic transformation involving the skin and lymph nodes. Four
      months after radiation therapy, he had full-blown acute myeloid leukemia. He
      received 2 cycles of Gemtuzumab ozogamicin (Mylotarg), allopurinol and
      hydroxyurea. Three months after initiation of chemotherapy, he deteriorated and
      received salvage chemotherapy of prednisone, VP-16 and imatinib mesylate
      (Gleevec). He was hospitalized for neutropenic fever and was diagnosed to have
      pulmonary aspergillosis. He died of multisystem failure 8 1/2 months after being
      diagnosed with AMM.

PMID- 15160963
TI  - Rituximab in a patient with acute renal failure due to B-cell lymphomatous
      infiltration of the kidneys.
AB  - Renal failure is known to occur in lymphoproliferative disorders because of
      ureteral obstruction or parenchymal infiltration by disease. Rituximab is a
      genetically engineered chimeric murine/human monoclonal antibody directed against
      the CD20 antigen found on the surface of normal and malignant B-lymphocytes. The
      pharmacokinetics and metabolism of rituximab is not well established. The extent
      of renal clearance is not fully known, with little experience reported on the use
      of rituximab in patients with renal failure. We present a case where rituximab
      was administered to a patient with acute renal failure due to bilateral kidney
      infiltration by non-Hodgkin's lymphoma (NHL). The patients renal function
      improved on therapy, with no need for hemodialysis and there were no significant
      toxicities. Rituximab may be used as a treatment option for NHL patients with
      impaired renal function.

PMID- 15160964
TI  - Plasma cell leukemia occurring in a patient with thrombocythemia treated with
      hydroxyurea and busulphan.
AB  - Plasma cell leukemia (PCL) is a rare aggressive lymphoproliferative disease with
      a short median survival and a very poor prognosis. We report the case of a 63
      year-old man who developed a PCL after 5 years of chemotherapy with hydroxyurea
      and busulphan for Essential thrombocythemia (ET). The karyotype showed a deletion
      of chromosome 7 and the plasma cells cytofluorimetric examination revealed a high
      expression of Multidrug Resistance related P-glycoprotein (PGP). After the second
      cycle of VAD chemotherapy the patient had a severe pneumonia and died with
      refractory PCL. This is a rare example of the coexistence of a chronic
      myeloproliferative and lymphoproliferative diseases in the same patient, and to
      the best of our knowledge, the first reported in the literature involving PCL and
      ET. Moreover, this case shows the possibility of secondary malignancies
      developing in patients treated with busulphan and hydroxyurea for chronic
      myeloproliferative disorders.

PMID- 15160965
TI  - Acute renal failure due to leukemic cell infiltration followed by relapse at
      multiple extramedullary sites in a child with acute lymphoblastic leukemia.
AB  - Acute renal failure due to leukemic infiltration into the kidney is rare in
      childhood acute lymphoblastic leukemia (ALL). We report here a five year-old boy
      with ALL who presented acute renal failure caused by leukemic infiltration at
      onset. Treatment with predonisolone and hemodialysis was effective. However, he
      showed persistent or repeated relapses at extramedullary sites, such as central
      nervous system, testis, and pancreas, suggesting that leukemic cells of this
      patient may have had a high affinity to extramedullary organs. On the basis of
      previous reports and the experience of this patient, intensive treatment may be
      needed in ALL children with renal involvement.

PMID- 15160966
TI  - Allogeneic bone marrow transplantation from an unrelated donor for the treatment
      of chronic myelogenous leukemia in blast crisis in a patient with Kleinfelter's
      syndrome.
AB  - We describe the first reported Klinefelter's syndrome (KS) in which allogeneic
      bone marrow transplantation from an unrelated donor (UR-BMT) was performed for
      treatment of chronic myelogenous leukemia in blast crisis (CML-BC). A 31-year-old
      male patient was diagnosed as having CML-BC with KS in April 2001. The result of
      a bone marrow chromosomal examination were 47, XXY, t(9;22)(q34;q11). After he
      had been treated with chemotherapy and imatinib mesylate, he underwent UR-BMT in
      February 2002. After the UR-BMT, his bone marrow chromosome changed from 47, XXY,
      t(9;22)(q34;q11) to 46,XY and 100% donor-type chimerism was obtained. However, he
      relapsed on day 83 after UR-BMT. After treatment with imatinib mesylate and
      tapering of immunosuppressive agents, skin and liver GVHD developed and then
      donor-type chimerism was increased with decreased blast cells. However, the
      patient died due to progression of disease in October 2002.

PMID- 15160967
TI  - T-cell lymphoblastic lymphoma presenting with a breast mass.
AB  - Lymphomas secondarily involving the breast are uncommon, although they do
      represent the largest group of tumors metastatic to breast. A 20-year-old female
      with lymphoblastic lymphoma (LBL) presented here with 3 month history of weight
      loss, night sweats, fatigue and a mass in her left breast. Her physical
      examination revealed a left breast mass, lympadenopathy, bilateral pleural
      effusion and hepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated.
      Breast ultrasound showed a 1.7 cm mass in the inner lower quadrant of left
      breast. Biopsy of the breast mass showed diffuse infiltration with small, round
      atypical cells which did not stain with CD20, CD43, CD34, cytokeratine and were
      positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL
      and treated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and
      prednisone), intrathecal methotrexate and cranial radiotherapy, achieving a
      complete response. She then was started on maintenance therapy. Four months later
      she returned with CNS involvement and was started on induction treatment. She had
      a very aggressive course of disease and died only 12 months after diagnosis.
      Breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this
      patient occurred secondarily as part of widespread disease.

PMID- 15160968
TI  - Primary Burkitt's lymphoma only involving the chest wall at relapse in a child.
AB  - Burkitt's lymphoma primarily originating from the soft tissue is a very rare
      neoplasm. A five-year-old boy was admitted with a mass on the lateral side of the
      right breast. Radiological examination revealed a mass, which had originated from
      the soft tissue of the chest wall without any contiguous pleural and lung
      parenchyma disease. Histopathology showed this to be Burkitt's lymphoma. To our
      knowledge, this case is the first instance of Burkitt's lymphoma presenting as an
      isolated chest wall mass which originated from the soft tissue.

PMID- 15160970
TI  - Primary granulocytic sarcoma of ovary--a rare presentation.
AB  - Granulocytic sarcomas (GS) are rare extra medullary tumors composed of myeloid
      progenitor cells. Bones, lymph nodes and skin are favored sites of involvement.
      Primary involvement of the ovary is exceedingly rare leading to under diagnosis
      of GS. We report on a 19-year-old woman who presented with an ovarian mass
      without any underlying hematologic disorder. A high index of suspicion aided by
      immunohistochemistry established the correct diagnosis.

PMID- 15160969
TI  - Systemic anaplastic large cell lymphoma presenting as a bladder neoplasm.
AB  - Non-Hodgkin's lymphoma is known to involve the bladder, either primarily or
      secondary. Anaplastic large cell lymphoma has not been documented at this site
      before. We report a case of a systemic anaplastic cell lymphoma in a 22-year-old
      man who presented with multisystemic symptoms and signs, including those
      suggestive of bladder disease. He was HIV-negative. Biopsy of the bladder showed
      a high grade lymphoma composed of large cells with nuclei containing prominent
      nucleoli. The tumor cells expressed CD30, CD45, EMA and ALK-1. A diagnosis of
      anaplastic large cell lymphoma, of null cell phenotype was made. The lymph node
      biopsy showed similar features on hematoxylin and eosin section. The patient was
      put on a regime of CHOP and is disease-free 33 months after diagnosis.

PMID- 15160972
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals. Case 24: striking
      lymphocytosis in a 2-year-old girl.

PMID- 15160971
TI  - Marked thrombocytosis in a child with advanced myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective
      hematopoiesis with rare occurrence in childhood. Conversely to adult affected
      patients, refractory anemia with ringed sideroblasts and the 5q-syndrome, which
      are associated with thrombocytosis are virtually absent in the pediatric age
      group. We describe the case of an 1-year-old boy with advanced MDS, specifically
      refractory anemia with excess of blasts who presented with leukocytopenia and
      anemia but marked thrombocytosis at diagnosis. Thrombocytosis resolved without
      therapy. This case illustrates the relationship between MDS and
      myeloproliferative disorders.

PMID- 15160973
TI  - Primary lymphoma of bone: a clinico-pathological review and analysis of
      prognostic factors.

PMID- 15160974
TI  - Breast and colorectal cancer risk communication approaches with low-income
      African-American and Hispanic women: implications for healthcare providers.
AB  - BACKGROUND: Information on breast and colorectal cancer risk factors is widely
      available to women and the physicians who provide their healthcare; however, many
      women are unable to identify the major risk factors, continue to misperceive
      their personal risk of developing these cancers, and do not engage in routine
      early detection. METHODS: Qualitative methods were used to investigate breast and
      colorectal cancer risk knowledge, perceptions, behaviors, and risk communication
      formats with low-income African-American and Hispanic study participants in
      Harlem, NY, aged 40-60 years. RESULTS: Focus group results indicated strong
      participant interest in strategies necessary to understand and reduce the risk of
      developing breast and colorectal cancers. Preferred risk communication tools
      presented information about family history and personal risk in graphic and
      quantitative formats. CONCLUSIONS: Healthcare professionals who serve low-income
      African-American and Hispanic female populations should deliver information to
      them about the personal risk of developing targeted cancers and ways to reduce
      this risk in formats that are meaningful and effectively address the special
      needs of these populations.

PMID- 15160976
TI  - Knowledge and awareness of hypertension among patients with systemic
      hypertension.
AB  - BACKGROUND: In Nigeria, systemic hypertension is the commonest noncommunicable
      disease, and public awareness about hypertension and its determinants is poor.
      This study aims to assess the knowledge and level of awareness of the disease
      among hypertensive patients attending the medical outpatient clinic of Olabisi
      Onabanjo University Teaching Hospital (OOUTH). METHODOLOGY: Hypertensive patients
      who attended the medical outpatient clinic during the one-year study period and
      gave their consent were recruited into the study. Response to a questionnaire on
      various aspects of hypertension was analyzed using the STATA for Windows
      software. RESULTS: There were 254 hypertensive patients, of which 111 were males
      and 143 were females, giving a male: female ratio of 1:1.3. The mean age (SD) of
      the patients was 51 years +/- 12.2; 52.4% of the participants were aware that
      hypertension was the commonest noncommunicable disease in Nigeria. About one in
      10 patients (11.4%) was aware that "nil symptom" is the commonest symptom of
      hypertension, while 37% were not aware that hypertension could cause renal
      failure. Only about one-third (35.4%) of the patients knew that hypertension
      should ideally be treated for life, while 58.3% believed that antihypertensive
      drugs should be used only when there are symptoms. The remaining 6.3% believed
      that the treatment of hypertension should be for periods ranging from two weeks
      to five years but not for life. CONCLUSION: This study has demonstrated
      inadequate knowledge of hypertension in patients with hypertension in our study
      population. Conscious efforts should be made and time set aside to health educate
      hypertensive patients. Organization of "hypertensive club or society" could be
      encouraged. These will reduce dissemination of false or inaccurate information by
      hypertensive patients to the public and its attendant dangers.

PMID- 15160975
TI  - Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a
      biological limit to possible reductions in morbidity and mortality.
AB  - We suggest that a particular form of social hierarchy, which we characterize as
      "pathogenic", can, from the earliest stages of life, exert a formal analog to
      evolutionary selection pressure, literally writing a permanent developmental
      image of itself upon immune function as chronic vascular inflammation and its
      consequences. The staged nature of resulting disease emerges "naturally" as a
      rough analog to punctuated equilibrium in evolutionary theory, although selection
      pressure is a passive filter rather than an active agent, like structured
      psychosocial stress. Exposure differs according to the social constructs of race,
      class, and ethnicity, accounting in large measure for observed population-level
      differences in rates of coronary heart disease across industrialized societies.
      American Apartheid, which enmeshes both majority and minority communities in a
      social construct of pathogenic hierarchy, appears to present a severe biological
      limit to continuing declines in coronary heart disease for powerful as well as
      subordinate subgroups: "Culture"--to use the words of the evolutionary
      anthropologist Robert Boyd--"is as much a part of human biology as the enamel on
      our teeth".

PMID- 15160977
TI  - Relation between region of residence in the United States and hypertension
      incidence--the NHANES I epidemiologic follow-up study.
AB  - A number of studies have found hypertension prevalence to be higher in the
      southeast region of the United States than in other U.S. regions. To test the
      hypotheses that hypertension incidence is higher in the southeast than in other
      regions, and that higher levels of known hypertension risk factors in the
      southeast explain the difference in incidence, data from a nationally
      representative, longitudinal cohort study of a sample drawn from the U.S.
      population, the NHANES I Epidemiologic Follow-Up Study (1971-1984), were
      analyzed. In the United States, age-adjusted relative odds of incident
      hypertension between 1971 and 1984 did not vary consistently with region or with
      urbanization level. There was only a trend of higher relative odds in
      nonmetropolitan areas than in suburbs in the southeast in younger white men and
      older white women. Thus, convincing evidence to support the hypothesis of
      elevated hypertension incidence in the southeast region or in nonmetropolitan
      areas was not obtained. Further studies of region and hypertension incidence are
      needed to assess regional variation in larger, more recent cohorts.

PMID- 15160978
TI  - Dyspepsia in African-American and Hispanic patients.
AB  - Dyspepsia is a common disorder with a prevalence of up to 40% in the general
      population. The presence of alarm features (age >50 years, loss of appetite,
      early satiety, loss of weight, dysphagia, abdominal mass, gastrointestinal
      bleeding, and/or anemia) increase the likelihood of an organic etiology. Despite
      a plethora of information written on this subject, the literature is sparse in
      minority populations. We studied the etiology of dyspepsia in relation to age and
      the presence or absence of alarm features in 678 African-American and Hispanic
      patients. Five-hundred-thirty patients were investigated by upper
      gastrointestinal (UGI) endoscopy, 88 by barium radiographs of the UGI tract, and
      60 patients had both endoscopy and barium studies. The most common alarm feature
      in our study was age >50 years, followed by anemia, weight loss, gastrointestinal
      bleeding, loss of appetite, early satiety, abdominal mass, and dysphagia. The
      presence of alarm features and older age increased the likelihood of finding an
      organic lesion. It is concluded, therefore, that endoscopy in our dyspeptic
      patients who had alarm features appears to increase the diagnostic yield and may
      consequently result in a more favorable therapeutic outcome.

PMID- 15160979
TI  - Serum ferritin levels and transferrin saturation in men with prostate cancer.
AB  - Elevated body iron stores (serum ferritin >300 microg/L, transferrin saturation
      TS >50%) are associated with increased risk of liver and lung cancers. To
      determine whether such association also exists for prostate cancer (PC), we
      measured serum ferritin, serum iron, total iron-binding capacity (TIBC), and TS
      in serum samples from 34 men with newly diagnosed, untreated PC and 84 healthy
      men, ranging in age from 49-78 years. In contrast with other malignancies, men
      with PC had significantly lower mean concentrations of serum ferritin (156
      microg/L) and TS (24.35%) than those without PC (ferritin, 245 microg/L; TS,
      31.98%) (p<0.05). The 95% confidence intervals for ferritin were 109-203 microg/L
      and 205-286 microg/L, and those for TS were 20.29-28.4% and 28.35-35.61% for men
      with and without PC, respectively. Significant differences were observed between
      both groups in the distribution of serum ferritin (<100, 101-300, >300 microg/L)
      and TS (<16, 16-50, >50%) (p<0.05). A lower percentage of cases than of controls
      had serum ferritin (17.6% versus 29.8%) and TS (5.9% versus 14.7%) above normal.
      These differences persisted when the analysis was limited to African-American men
      (31 cases and 52 controls). Data suggest that elevated body iron stores are less
      common in men with PC compared to those without PC.

PMID- 15160980
TI  - Prostate cancer knowledge among multiethnic black men.
AB  - The purpose of this survey of 528 black men in Miami and Fort Lauderdale, FL, was
      to assess prostate cancer knowledge among African-American, English-speaking
      Caribbean, Haitian-American, and African men in America. Knowledge levels were
      assessed by education, ethnicity, age, income, family history of prostate cancer,
      and perceived prostate cancer knowledge. Twenty-five barbershops were visited
      during Fridays, Saturdays, and Sundays over a course of five months. The response
      rate was 99%. As the black men waited to be seen by their barbers, three
      interviewers asked them to answer the demographic and knowledge questions. SPSS
      was used to analyze the data. The main findings were that knowledge levels were
      adequate, with mean correct responses being 68.4%. Approximately 19.1% of
      respondents answered 80% of questions correctly, and 7.1% answered 100% of
      questions correctly. There were no statistically significant differences in
      knowledge among black men of different ethnicities. There were only two factors
      which were significantly related to prostate cancer knowledge. Men who earned
      more than dollars 50,000 and those with a family history of prostate cancer
      scored significantly higher than lower-income men and men with no family history
      of prostate cancer. As the percentage of Caribbean-American men and African men
      in the United States continues to increase, especially in metropolitan centers,
      those men at highest risk need to be targeted vigorously so that the
      disproportionate burden of prostate cancer on black men can be relieved.

PMID- 15160981
TI  - Natural history of multifocal solitary fibrous tumors of the pleura: a 25-year
      follow-up report.
AB  - We report this case with "multifocal solitary fibrous tumors of the pleura,"
      which recurred at different sites in the left pleura at different time intervals
      over a span of 25 years, finally exhibiting features of malignant transformation.
      This patient was first seen in 1978, when she was 58 years of age, for episodic
      attacks of hypoglycemia and a mass occupying the entire left hemithorax. The
      operative findings and histologic appearance were that of a solitary fibrous
      tumor.

PMID- 15160982
TI  - Chatting behavior and patient satisfaction in the outpatient encounter.
AB  - Communication studies suggest that patient sociodemographic factors are embedded
      within medical encounters and impact patient expectations, judgments, and
      outcomes, such as satisfaction. Physician chatting has been suggested as one way
      to enhance patient satisfaction; however, little is known about chatting within
      the context of the clinical encounter or of the interaction of chatting with
      patient sociodemographic factors and patient satisfaction. The study's purpose
      was to determine the prevalence and patterns of chatting, and to examine the
      association of chatting with patient sociodemographic factors and patient
      satisfaction with their physician. A convenience sample of adult outpatients from
      an urban family practice underwent an exit interview. A total of 105 patients
      participated; 63 (61%) reported chatting from their recent encounter. No
      sociodemographic differences were observed between patients reporting chatting
      and those reporting no chatting. Chatting behavior pertaining to the patient's
      family or friends was the predominant topic, and more nonwhite (30%) than white
      (13%) patients reported this activity (p<0.001). There was no significant
      difference in satisfaction scores between patients that reported chatting
      behavior and those that did not (23.73 vs. 22.79, p=0.076). In addition, there
      was no difference in patient satisfaction scores for physician personal manner,
      technical skill, visit explanation, time spent with the physician, and overall
      visit between the chatting and nonchatting groups.

PMID- 15160983
TI  - Amebiasis and comparison of microscopy to ELISA technique in detection of
      Entamoeba histolytica and Entamoeba dispar.
AB  - The analysis of records of amoebal infection in various hospitals in Kilimanjaro
      indicated frequent occurrence of amebiasis. The population over the age of five
      years had higher rate of amoebal infection compared to less than that of a five
      year-old population; however, both age groups had similar patterns of amebiasis
      during January 1999 to June 2001. To investigate misdiagnosis of amebiasis, 226
      patients (passive cases) in three hospitals and 616 individuals (active cases)
      from three different localities in Kilimanjaro were examined. In passive cases,
      the prevalences of Entamoeba histolytica and Entamoeba dispar were 1% and 7.3%,
      respectively. Among active cases, 1% were infected with E. histolytica, and 15%
      were infected with E. dispar. There were no significant differences in amoebal
      infection between the male and female populations. A pool of 842 stool samples
      was used for diagnosis of E. histolytica and E. dispar by microscopic examination
      or ELISA kits. The microscopic examination indicated 8.7% amoebal infection;
      however, using ELISA as the gold standard, the prevalence of histolytica/dispar
      was 0.8% and 7.4%, respectively. This study indicated that E. dispar infection
      was 14.5 times more prevalent than E. histolytica infection.

PMID- 15160985
TI  - Cervico-mediastinal tuberculous lymphadenitis presenting as prolonged fever of
      unknown origin.
AB  - Prolonged fever of unknown origin (FUO) is a challenging and important medical
      problem. Tuberculosis is the most frequent cause of FUO, especially in endemic
      regions, such as developing countries. We present a case of cervico-mediastinal
      tuberculous lymphadenitis that had been searched and followed up as a prolonged
      FUO. Especially in endemic areas, tuberculosis should be borne in mind in the
      differential diagnosis of FUO cases with granulomatous lymphadenitis presenting
      as prolonged or recurrent fever, even if the cultures and polymerase chain
      reaction for Mycobacterium tuberculosis are negative.

PMID- 15160984
TI  - The choice of arthroplasty for secondary osteoarthritis of the hip joint
      following avascular necrosis of the femoral head in sicklers.
AB  - Secondary osteoarthritis of the hip joint often complicates avascular necrosis of
      the femoral head in young adults suffering from sickle cell anemia. These
      patients, particularly in our environment, are usually reluctant to use walking
      aids like crutches to alleviate the pain since they believe that these devices
      are temporary measures. They often demand long-term solutions which border on
      surgery. The surgical procedures carried out in these patients range from
      osteotomies to arthroplasties. With the advent of various forms of hip implants,
      osteotomies are not as popular in modern-day orthopedic practice. In this series,
      we treated five patients with secondary osteoarthritis in six hip joints
      (bilateral in one patient) using cementless bipolar arthroplasty with good
      outcome. This implant is available and affordable in Nigeria, and the use of a
      cementless implant obviates damage to the acetabulum and may make revision
      surgeries less hazardous both for the surgeon and the patient.

PMID- 15160986
TI  - March of Dimes prematurity campaign: a call to action.

PMID- 15160987
TI  - How could we solve the diagnostic dilemma of doxorubicin toxicity in high-risk
      patients?

PMID- 15160988
TI  - Cardiotoxic drugs in breast cancer.

PMID- 15160989
TI  - Peer, parental, and commercial influences on cigarette smoking among Chinese
      youths.

PMID- 15160990
TI  - Potential adverse effects and inferior efficacy in ARV treatment.

PMID- 15160991
TI  - Histone deacetylase inhibitors enhance paclitaxel-induced cell death in ovarian
      cancer cell lines independent of p53 status.
AB  - BACKGROUND: Recurrence of drug-resistant disease contributes to the high
      mortality of ovarian cancer patients, which necessitates the identification of
      additional chemotherapeutic drugs. Histone deacetylase inhibitors (HDAIs) induce
      apoptosis in a number of malignant cell types and may represent a new class of
      drugs clinically relevant in the treatment of ovarian cancer. MATERIALS AND
      METHODS: Ovarian cancer cells were treated with various combinations of a HDAI
      and paclitaxel (PTX). Cell death was measured using annexin V/propidium iodide
      exclusion. RESULTS: The PTX/HDAI drug combination was as efficient in inducing
      cell death as continuous PTX treatment and superior to continuous HDAI treatment.
      Reversing the sequence of drug exposure reduced the cytotoxic efficacy of the
      drug combination. The p53 status of the cell lines did not alter the cytotoxic
      efficacy of the treatment protocols. CONCLUSION: These results suggest that HDAIs
      possess possible clinical applications as an adjuvant therapy in the treatment of
      ovarian cancer.

PMID- 15160992
TI  - Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in
      human glioma.
AB  - We studied whether the expression of the Neuropilin (NRP) gene was correlated
      with clinicopathological features in glioma. We examined the gene expression of
      vascular endothelial growth factor (VEGF)-A, Flt-1, KDR, NRP1 and NRP2 in 37
      gliomas by real time reverse transcriptase PCR (real time RT-PCR) as well as
      immunohistochemical analysis. The vascular counts of each tumor were evaluated by
      anti-CD34 antibody. NRP1 mRNA overexpression was significantly higher in
      neoplastic tissue compared to normal brain tissue samples. The higher grade of
      glioma overexpressed the NRP1 gene significantly (p=0.0015). The glioma patients
      with NRP1 overexpression showed a poorer prognosis (p=0.0202) than those without
      such overexpression. NRP1 was observed in the glioma cells by immunohistochemical
      analyses. VEGF-A and VEGFR overexpression did not show any correlation with the
      clinicopathological features, including NRP expression. These results suggest
      that NRP1 overexpression, rather than VEGF-A or VEGFR, contributes to tumor
      progression and has clinical significance for glioma.

PMID- 15160993
TI  - Molecular pathogenesis and prevention of prostate cancer.
AB  - Studies in laboratory animals indicate inhibition of chemically-induced carcinoma
      by cystine-rich diets enhancing the cysteine-GSH antioxidant system. The
      progression of carcinoma of the prostate is also inhibited by these diets, which
      were later found to raise the level of GSH in the prostate epithelium of man. New
      data presented at the July 13, 2003 meeting of the American Association for
      Cancer Research indicates that higher levels of total cysteine in plasma may
      predict a reduced risk for breast cancer. This prospective investigation was
      conducted among 32,000 women in the Nurses Health study. The previously reported
      prostate cancer data appears then not to be strictly gender-related as the
      antioxidant role of the cysteine-GSH system may also apply to breast cancer
      prevention.

PMID- 15160994
TI  - Ionizing radiation inhibits the PLK cell cycle gene in a G2 checkpoint-dependent
      manner.
AB  - Tumor cell cycle arrest at the cell cycle G2/M boundary after ionizing radiation
      involves inhibition of the Polo-like kinase 1 (Plk1). We recently found that the
      mechanism comprised repression of its gene, PLK, mediated by the tumor-suppressor
      protein BRCA1. In the present study we examined the regulatory responses on PLK
      and cell cycle phases in breast carcinoma cell lines exposed to various modes of
      therapeutic irradiation. The tumor cells, harboring different DNA damage
      checkpoint defects, were irradiated with either a single dose of 8.0 Gy or
      fractionated doses accumulating to 8.0 Gy. In the BRCA1-/- HCC1937 cell line both
      radiation regimens caused moderate repression of PLK mRNA expression, whereas the
      reconstituted wild-type (wt) BRCA1 genotype of the HCC1937/BRCA1wt cell line was
      associated with significant down-regulation of PLK mRNA expression after
      irradiation. In contrast to the HCC1937 cell lines, the MCF7/LCC2 cells displayed
      the characteristic wt TP53 constitution of persistent, radiation-induced CDKN1A
      mRNA expression (encoding the G1 cell cycle inhibitor p21(Waf1/Cip1/Sdi1)). The
      regulatory effects on PLK in the MCF7/LCC2 cells, however, were identical to
      those in the HCC1937/BRCA1wt cell line. Moreover, whereas neither HCC1937 cell
      line displayed G1/S cell cycle arrest after irradiation but, instead, an apparent
      accumulation of G2/M-phase cells, the radiation-induced delay at the G1/S
      boundary seemed to be superior to arrest at the G2/M transition in the MCF7/LCC2
      cell line. Since the down-regulation of PLK mRNA expression by ionizing radiation
      was identical in the wt TP53 MCF7/LCC2 cell line and the TP53-mutated BRCA1-/-
      HCC1937 cell line reconstituted with wt BRCA1, we conclude that this regulatory
      effect solely requires an intact G2 checkpoint effector mechanism.

PMID- 15160995
TI  - Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin
      and related compounds.
AB  - The cytotoxicity, ROS (reactive oxygen species)-generation activity and radical
      scavenging activity of curcumin and related compounds such as eugenol, eugenol
      orthodimer (bis-eugenol; 3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'
      diol) and isoeugenol were investigated. Their cytotoxicity against a human
      submandibular gland adenocarcinoma cell line (HSG) declined in the order curcumin
      > isoeugenol > bis-eugenol > eugenol. Since the hydrophobicity (log P) of
      curcumin, isoeugenol and eugenol is about 2.5, whereas that of bis-eugenol is
      4.8, there was no relationship between cytotoxicity and log P. Generation of
      intracellular ROS in HSG cells was observed for curcumin alone in an assay using
      5- (and -6)-carboxy-2',7'-dichlorofluorescein diacetate (CDFH-DA). The
      cytotoxicity of, and ROS generation by, curcumin were reduced by the addition of
      N-acetyl-L-cysteine (NAC) and glutathione, suggesting a possible link between
      cytotoxicity and ROS. The radical-scavenging (antioxidant) activity of curcumin
      and related compounds was determined quantitatively by the induction period
      method for polymerization of methyl methacrylate (MMA) initiated by peroxy
      radicals derived from benzoyl peroxide (BPO) under nearly anaerobic conditions.
      The length of the induction (inhibition) period for curcumin was significantly
      greater than that of the other compounds. This suggests that curcumin is an
      efficient scavenger of peroxy radicals. The curcumin radical possibly reacts with
      itself or with other radicals to yield polymeric stable products such as curcumin
      dimer. Such polyphenolic behavior of curcumin was considerably different from
      that of bis-eugenol, which, like curcumin, has two hydroxy groups, or of other
      compounds with one hydroxy group. The radical-scavenging activity was also
      investigated with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Curcumin scavenged
      approximately one DPPH free radical, suggesting the formation of curcumin dimer.
      The possible formation of curcumin dimer was explored with a PM3 semiempirical
      molecular orbital method. A molecular mechanism of cancer prevention by curcumin
      is proposed, based on its high reactivity with peroxy radicals at low oxygen
      pressure and on ROS generation induced by curcumin radicals.

PMID- 15160997
TI  - Cellular parameters predictive of the clinical response of colorectal cancers to
      irinotecan. A preliminary study.
AB  - BACKGROUND: We have examined, in this study, the feasibility of determining
      cellular factors contributing to irinotecan activity in colorectal cancers.
      Irinotecan is a camptothecin derivative requiting carboxylesterase activation to
      SN-38, which interacts with its target enzyme, topoisomerase I. MATERIALS AND
      METHODS: In 9 surgical or biopsy samples of colorectal tumours and corresponding
      normal tissue, kept in a tumour bank, we evaluated topoisomerase I expression and
      activity, respectively by Western blotting and DNA relaxation assay,
      carboxylesterase activity using two different substrates and p53 status by
      immunohistochenistry. RESULTS: Topoisomerase I expression and activity were
      significantly correlated, as were the two types of determinations for
      carboxylesterase activity. Topoisomerase I was significantly more active in
      tumours than in corresponding normal tissue. The three samples presenting the
      highest topoisomerase I expression and activity originated from the patients who
      responded to irinotecan treatment. No such features were apparent for
      carboxylesterase activity and p53 staining. CONCLUSION: Topoisomerase I
      expression appeared as the parameter most likely to predict response to
      irinotecan therapy in the clinical setting.

PMID- 15160996
TI  - Cytotoxic T cell induction against human malignant melanoma cells using HLA-A24
      restricted melanoma peptide cocktail.
AB  - Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide
      specific cytotoxic T cells (CTLs) have been derived from peripheral blood
      lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA
      A*2402-restricted melanoma-associated peptides have been performed, because HLA
      A24 is not a common allele in Caucasians. In this study, we investigated the
      specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from
      gp100, tyrosinase, MAGE1, MAGE2 and MAGE3. A CTL induction culture was performed
      using PBLs and cultured dendritic cell (DC) pulsed with HLA-A*2402-restricted
      melanoma peptide cocktail. The CTLs derived from volunteers killed the A24
      peptide-pulsed TISI cells and even HLA-A*2402-positive melanoma cells, but not
      HLA-A*0201-positive cells. IFN-gamma levels produced by the melanoma patients'
      CTLs were obviously low in each peptide group compared with those produced by the
      volunteers' CTLs, which indicated the presence of immunosuppressive factors in
      metastatic melanoma. These results suggested that polyvalent immunotherapy using
      multiple epitopes from melanoma antigens might be a better way of improving the
      efficacy of treatment.

PMID- 15160998
TI  - The colon mitosis inhibitor pyroglutamyl-histidyl-glycine inhibits growth of non
      tumorigenic colonic epithelial cells.
AB  - BACKGROUND: The colon mitosis inhibiting peptide pyroglutamyl-histidyl-glycine
      (pEHG) increases the expression of c-fos, fosB and egr-1 genes in the colon
      carcinoma cell line HT-29. However, the effect on non-tumorigenic colonic cells
      has not been investigated. MATERIALS AND METHODS: After exposure of the cell
      lines YAMC (from colon mucosa of Immorto mice) and IMCE (fromn Immorto-Min mouse
      hybrid) to pEHG, DNA-synthesis was analysed by H3-thymidine incorporation,
      apoptosis and necrosis by fluorescence microscopy, and cell cycle distribution by
      flow cytometry. RESULTS: pEHG inhibited DNA-synthesis with a maximal effect at
      10(-8)-10(-9) M, but stimulated at 10(-4) M. It blocked cell flow through the
      cell cycle at GC/M after 8 h of treatment, but had no effect on apoptosis or
      necrosis at any concentration. A low concentration of ascorbic acid stabilised
      the cells, maybe as a free radical scavanger. CONCLUSION: pEHG inhibits flux at
      the G2/M transition, but has no effect on cell death.

PMID- 15160999
TI  - Overlapping functions of Ras and Rac GTPases in regulating cancer cell
      proliferation and invasion.
AB  - The mechanism by which the Ras and Rac GTPases and the mitogen activated protein
      kinase cascade regulate cancer cell proliferation and invasion has been an
      intense area of investigation. A great diversity of membrane receptors and
      upstream regulators activate the Ras and Rac GTPases. It has been recognized that
      Ras and Rac GTPases regulate a set of cellular responses including gene
      expression, cellular proliferation and motility. In human cancer, constitutively
      active Ras mutations may contribute to deregulated cell proliferation and
      invasion. Rac has been shown to be an essential partner in Ras-mediated
      transformation. While these studies have been very important in increasing our
      understanding of the roles of Ras and Rac, many human cancer cells do not contain
      Ras and Rac mutations yet show increased activation of the downstream target
      ERK1, proliferate rapidly in vitro and in vivo and readily penetrate
      semipermeable membranes. We characterized human squamous cell carcinoma lines
      that do not contain H-Ras or Rac1 mutations but express high levels of activated
      ERK1. To delineate the functions of Ras and Rac in these cells, we were able to
      stably express dominant negative Ras and Rac1 constructs in one of these lines.
      Both dominant negative Ras and Rac1 constructs inhibited proliferation of these
      clones by regulating a similar set of cell cycle proteins. Both dominant negative
      constructs inhibited basal and growth factor-induced levels of cellular
      migration. We concluded that Ras and Rac1 have overlapping functions in cancer
      cell proliferation and migration.

PMID- 15161000
TI  - Expression of hyaluronan synthases and hyaluronan in malignant mesothelioma
      cells.
AB  - BACKGROUND: Hyaluronan is one of the main components of the extracellular matrix.
      It is synthesized at the cell plasma membrane by specific hyaluronan synthases
      (HAS). Although a large number of studies have described hyaluronan in pleural
      effusion from malignant mesothelioma, the source of hyaluronan in malignant
      mesothelioma has been subject to controversy. MATERIALS AND METHODS: The mRNA
      expression of all three HAS in malignant mesothelioma cells was studied using RT
      PCR. The hyaluronan production in culture medium of malignant mesothelioma cells
      was also examined using high-performance liquid chromatography (HPLC). RESULTS:
      We found that 9/10 malignant mesothelioma cell lines and one primary culture of
      malignant mesothelioma cells expressed HAS-1, while 10/10 malignant mesothelioma
      cell lines and one primary culture of malignant mesothelioma cells expressed HAS
      2 and HAS-3. In addition, we demonstrated hyaluronan in the culture medium of 6
      out of 10 malignant mesothelioma cell lines and one primary culture of malignant
      mesothelioma cells. CONCLUSION: Our results show that malignant mesothelioma
      cells express all three HAS and synthesize hyaluronan. The expression of HAS
      isoforms and hyaluronan in malignant mesothelioma cells in cultures and previous
      observations by other investigators indicate that these cells are, at least in
      part, responsible for hyaluronan synthesis in vivo.

PMID- 15161001
TI  - Suppression of Lewis lung tumor development in alpha 1,3 galactosyltransferase
      knock-out mice.
AB  - BACKGROUND: Humans lack the gene alpha 1,3 galactosyltransferase (GalT) and
      instead produce abundant cytolytic antibodies against cells bearing the antigen
      [gal alpha1,3 gal] (alphaGal). We have previously studied humoral anti-alphaGal
      responses in GalT knock-out (GalT KO) mice and shown that murine anti-alphaGal
      IgM, like human anti-alphaGal IgM, causes extensive complement-mediated cytolysis
      of GalT+ murine Lewis Lung carcinoma cells (LLCa) in vitro. Here we test the
      hypothesis that anti-alphaGal immune responses can inhibit the in vivo
      development of GalT+ tumors. MATERIALS AND METHODS: GalT KO mice orally immunized
      to produce anti-alphaGal antibodies (n =52) and naive non-immunized KO mice
      (n=37) were challenged s.c. with 10(5) LLCa tumor cells. Anti-alphaGal antibody
      titers were measured before and after LLCa challenge. RESULTS: Anti-alphaGal IgM
      titers present at challenge correlated with protection from tumor development
      (p<0.04). Seventy-five percent of mice with titers > or = 1:1280 remained tumor
      free versus 43% of naive mice. Tumor onset was delayed in mice with circulating
      anti-alphaGal IgM versus naive animals (p=0.02). LLCa challenge itself induced
      and augmented anti-alphaGal IgM and post-challenge titers correlated highly with
      protection from tumor development (p<0.001). No mice with post-challenge anti
      alphaGal IgM titers > or = 1:1280 developed tumors, compared to 83% of mice
      lacking antibody. Inhibition studies showed that 30% of post-challenge IgM
      recognized LLCa antigens distinct from alphaGal. Anti-alphaGal IgG was low or
      undetectable both pre- and post challenge and did not affect tumor formation.
      CONCLUSION: The finding that anti-alphaGal IgM suppresses GaIT+ tumor development
      in vivo supports the premise that immunotherapy using GalT expression can utilize
      human anti-alphaGal responses and induce significant anti-tumor effects.

PMID- 15161002
TI  - Comparison of human tumour cell responses to cisplatin and ZD0473 with and
      without irradiation.
AB  - Three pairs of human tumour cell lines, with one line of each pair resistant to
      cisplatin, were used to compare the effects of cisplatin and ZD0473 on cellular
      toxicity and radiosensitization. Whilst all three cell line pairs had one line
      that was resistant to cisplatin, for ZD0473 the lung tumour HTB56cp and cervical
      carcinoma ME180 cell lines did not express resistance to their HTB56 and SHA
      counterparts, respectively. Only the ovarian carcinoma line A2780cp showed
      resistance to ZD0473 compared to its counterpart A2780S. For radiosensitization
      both cisplatin and ZD0473 show additive and subadditive effects in the ovarian
      carcinoma lines, and additive and superadditive effects in the cervical carcinoma
      and lung tumour cell lines. In fact in the lung tumour cell lines ZD0473 appeared
      to be a more effective radiosensitizer than cisplatin.

PMID- 15161003
TI  - Effects of oral squamous cell carcinoma-derived TGF-beta1 on CD26/DPPIV
      expression in T cells.
AB  - BACKGROUND: Enzymatic activity levels of serum CD26/dipeptidylpeptidase (DPP) IV
      in oral cancer patients are lower than those in healthy subjects. However, the
      mechanism for this decrease is not yet fully understood. MATERIALS AND METHODS:
      The influence of malignant cell-derived cytokines on cell surface CD26/DPPIV
      expression in human T cells was analyzed using an oral squamous cell carcinoma
      (SCC) cell line, KB, and peripheral blood T cells. RESULTS: Tumor growth factor
      (TGF)-beta1 in KB-conditioned medium (KBCM) down-regulated CD26/DPPIV expression
      in T cells, which was responsible for the decreased DPPIV activities in the
      cultured supernatant. Expression p27kip in T cells was maintained in addition to
      G1 arrest when cultured with KBCM but was abolished by inclusion of anti-TGF
      beta1 antibody. CONCLUSION: SCC-derived TGF-beta1 down-regulates CD26/DPPIV
      expression in T cells, resulting in decreased serum CD26/DPPIV activity in oral
      cancer patients.

PMID- 15161004
TI  - Preliminary study of the optimal dosing schedule for oral UFT/leucovorin
      chemotherapy.
AB  - BACKGROUND: We evaluated the optimal dosage schedule for combined oral
      chemotherapy using uracil/tegafur (UFT) and leucovorin (LV) in Yoshida sarcoma
      bearing rats. MATERIALS AND METHODS: The antitumor activity and survival effect
      were compared between two schedules, thrice daily administration on 5 days of the
      week followed by 2 drug-free days (schedule A) and twice daily on 7 days of the
      week (schedule B). RESULTS: Significant tumor growth inhibition and improved
      survival rate were seen with both schedules of the UFT/LV group as compared to
      their respective control groups. Tumor growth inhibition was significantly
      greater in schedule A than schedule B. The number of survivors on day 60 after
      the tumor inoculation was higher in schedule A although the survival rate did not
      differ significantly. CONCLUSION: Administration of UFT/LV for 5 days of the week
      seemed to exhibit superior antitumor activity, with no increase in the incidence
      of adverse effects, as compared with the consecutive daily dosing schedule.

PMID- 15161005
TI  - Taurolidine-Fibrin-Sealant-Matrix using spray application for local treatment of
      brain tumors.
AB  - Malignant gliomas tend to recur in the vast majority of cases. Recurrent gliomas
      may arise from vital tumor cells present in this zone around the resection
      margin. It appears promising to combine tumor resection with local chemotherapy
      using an antineoplastic, but non-toxic agent. Taurolidine exerts a selective
      antineoplastic effect by induction of programmed cell death and has anti
      angiogenic activity. Fibrin sealant is completely degradable and firmly adheres
      to brain tissue, suggesting that it would provide a suitable matrix for
      taurolidine delivery--a Taurolidine-Fibrin-Sealant-Matrix (TFM)--in the local
      treatment of brain tumors. The potential of local delivery of taurolidine out of
      a fibrin sealant matrix was investigated. Taurolidine could be suspended
      homogeneously in both the thrombin and the procoagulant protein components of the
      fibrin sealant. The fibrin sealant matrix was a suitable carrier for the
      suspension of taurolidine at a concentration that ensured the release of
      therapeutically effective amounts of the drug over a period of 2 weeks in vitro.
      The antineoplastic action of taurolidine was not affected by embedding in the
      fibrin sealant matrix. The described drug delivery system may be suitable for
      local taurolidine treatment of brain tumors following complete or partial
      resection or of tumors that are non-resectable because of their location.

PMID- 15161006
TI  - Enhancing effect of PS-K on IL-2-induced lymphocyte activation: possible
      involvement of antagonistic action against TGF-beta.
AB  - Effects of protein-bound polysaccharide (PS)-K on interleukin (IL)-2-induced
      responses of peripheral blood mononuclear cells (PBMCs) were studied. PS-K (50
      mcg/ml) was observed to enhance proliferative responses, cytotoxic activities
      against K562 and Daudi target cells, CD25+ cell population and telomerase
      activity of PBMCs stimulated with IL-2. The cytotoxic effector cells could be
      generated in the presence of PS-K even with a minimum amount of IL-2. The
      enhancing effect of PS-K on the IL-2-induced lymphocyte activation was more
      evident in PBMCs from cancer patients than in those from healthy volunteers,
      suggesting that PS-K may be beneficial if combined in the IL-2-based
      immunotherapy of cancer. TGF-beta inhibited the IL-2-induced lymphocyte
      activation of proliferative responses, cytotoxic activities and CD25+ cell
      population, the inhibitions of which were abrogated with PS-K. PS-K also
      abrogated the TGF-beta-induced anchorage-independent growth of normal rat kidney
      cells. Flow cytometric analysis using a labeled TGF-beta revealed that PS-K
      blocked the binding of TGF-beta at its receptor level on the surface of PBMCs. It
      is suggested that PS-K enhances IL-2-induced lymphocyte activation through, in
      part, an antagonistic action against TGF-beta.

PMID- 15161007
TI  - The association between methylenetetrahydrofolate reductase polymorphism and
      promoter methylation in proximal colon cancer.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in
      folate metabolism, which is an important pathway of the methyl donor for DNA
      methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause
      reduced enzyme activity. Impaired folate metabolism by these genetic variants of
      MTHFR could change the methylation pattern of DNA including promoter
      hypermethylation, which has been frequently observed in cancer. In this study, we
      compared the MTHFR genotypes and haplotype to the features of colorectal cancer
      focusing on the promoter methylation of tumor DNA. MATERIALS AND METHODS: Genomic
      DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR
      genotyping by PCR-based restriction fragment length polymorphism analysis. The
      MTHFR haplotype was determined by combination of C667T and A1298C genotype and
      classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic
      activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A,
      hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation
      specific PCR method. RESULTS: There was no significant association of the
      clinicopathological features with either C667T genotype, A1298C genotype or
      haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the
      L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal
      origin were considered (p=0.029). hMLH1 methylation also tended to be higher in
      proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal
      colon cancers showing CpG island methylator phenotype (CIMP) were significantly
      more frequent in L-haplotype than in H-haplotype. CONCLUSION: These results
      suggest that the haplotype with low enzymatic activity of MTHFR is linked with
      promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal
      colon cancer development in the Japanese people. The relationship between MTHFR
      polymorphism and DNA methylation in the Japanese is contrary to the previous
      results in Caucasians. Further study is needed focusing on ethnic variations in
      the relationships among MTHFR polymorphism, DNA methylation and the development
      of CIMP(+) colorectal cancer.

PMID- 15161008
TI  - Apoptosis-inducing activity of cisplatin (CDDP) against human hepatoma and oral
      squamous cell carcinoma cell lines.
AB  - The sensitivity of human hepatoma (HepG2) and oral squamous cell carcinoma (HSC
      2) cell lines against various apoptosis-inducing agents was compared. HepG2 cells
      were generally more resistant to an oxidant (H2O2), antioxidants (sodium
      ascorbate, gallic acid, epigallocatechin gallate) and anticancer drugs
      (doxorubicin, methotrexate, cisplatin (CDDP), etoposide, 5-fluoro-2,4(1H,3H)
      pyrimidinedione (5-FU), peplomycin sulfate) as compared to HSC-2 cells. Lower
      concentrations of CDDP, but not other anticancer drugs, induced comparable
      cytostatic effects on both HSC-2 and HepG2 cells. CDDP induced internucleosomal
      DNA fragmentation and activation of caspases 3, 8 and 9 in HepG2 cells. On the
      other hand, CDDP did not induce DNA fragmentation and activated caspase 3 only
      marginally in HSC-2 cells. Combination treatment with CDDP (10 microM) and 5-FU
      (100 microM) additively activated all three caspases in HepG2 cells, but not in
      HSC-2 cells. The present study demonstrated the chemotherapeutic potential of
      combined treatment of CDDP and 5-FU against hepatoma cells and the considerable
      variation of drug sensitivity between cancer cell lines.

PMID- 15161009
TI  - Efficient targeting of gastric cancer cells using radiolabeled anti
      carcinoembryonic antigen-specific T84.66 fragments in experimental
      radioimmunoguided surgery.
AB  - BACKGROUND: Radioimmunoguided surgery (RIGS) appears as an efficient tool for
      accurate tumor detection up to the level of micrometastases by detecting
      radiolabeled antibody-bound tumor cells during operation. Anti-CEA-specific
      T84.66 fragments were examined as to whether they efficiently detected gastric
      cancer cells in experimental RIGS. T84.66, anti-CEA-specific antibody, has widely
      been used as an immune carrier in the preclinical and clinical trials of
      radioimmunotherapy and radioimmunoscintiscan. MATERIALS AND METHODS: Fifty-one
      tumors from two human gastric carcinoma cell lines with profuse (MKN45) and low
      (RF48) CEA expression were successfully implanted subcutaneously in the backs of
      32 nude mice. Tumors were localized after 125I-labeled T84.66 F(ab')2 and Fab'
      injection. RESULTS: The radioactivity of F(ab')2-pretreated mice was greater than
      that of Fab'-pretreated in all organs and tumors (p<0.001-0.035). Localization
      indices of the tumor in various organs revealed 7.4 to 32.5 in F(ab')2-pretreated
      and 1 to 7.1 in Fab'-pretreated mice. Silver grains and immune staining were
      predominantly distributed in tumor cells regardless of fragment types and cell
      lines. There was no false-negative evaluation of tumor in F(ab')2-pretreated
      mice. Sensitivity and specificity of tumor localization by RIGS were the highest
      in the F(ab')2-pretreated mice (95% for MKN45- and 82% for RF46-xenografted mice)
      and the least in the Fab'-pretreated mice (66% for MKN45- and 67% for RF46
      xenografted mice). In all organs, three quarters of the false-positive
      evaluations occurred from silver grains as radioimmune complex or dissociated
      nuclides in the circulation that can be eliminated with time. CONCLUSION: Anti
      CEA-specific T84.66 fragments achieved a great affinity and avidity with accurate
      localization of gastric carcinoma in experimental RIGS.

PMID- 15161011
TI  - Increased nuclear factor-kB activation in human colorectal carcinoma and its
      correlation with tumor progression.
AB  - OBJECTIVES: Nuclear factor-kB (NF-kB) is a transcription factor that participates
      in the induction of several genes for cytokines and enzymes that play important
      functional roles in various cell types. The aim of this study was to determine NF
      kB activation status in human colorectal carcinoma and its correlation to the
      clinicopathological characteristics of patients. MATERIALS AND METHODS: We
      examined the activation status of NF-kB in 28 resected colorectal carcinomas and
      in colonic mucosa from uninvolved portions of these specimens by electrophoretic
      mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit
      of NF-kB. RESULTS: EMSA showed much greater activation in the tumors than in
      normal mucosa, as did epithelial p65 immunostaining. NF-kB activation
      significantly increased in the more progressed cases (T3 + T4 cases or Stage II<
      cases). In vitro studies using lipopolysaccharide (LPS)-responsive colon
      carcinoma cells suggested a correlation between NF-kB activation and cell
      proliferation. CONCLUSION: Our findings indicated that NF-kB is constitutively
      activated in human colorectal carcinoma tissue and correlates with tumor
      progression. The regulation of this transcription factor might be therapeutically
      useful against these tumors.

PMID- 15161010
TI  - Different expression of cyclooxygenase-2 in biliary epithelia of bile duct cancer
      with or without pancreaticobiliary maljunction.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) has been reported to play an important role
      in the pathogenesis of a variety of cancers. Little is known about the
      relationship between bile duct cancer associated with pancreaticobiliary
      maljunction (PBM) and COX-2. MATERIALS AND METHODS: We compared the expression of
      COX-2 in bile duct epithelium in bile duct cancer with or without PBM. RESULTS:
      Immunohistochemical analysis showed that the rate of positive COX-2 expression
      was 42.9% for cancerous lesions and 7.1% for noncancerous lesions in cases of
      bile duct cancer without PBM. On the other hand, no positive expression of COX-2
      was observed in cancerous lesion of bile duct cancer with PBM. Twenty % of the
      noncancerous bile duct mucosa with PBM was positive for COX-2. CONCLUSION: COX-2
      is expressed in bile duct cancer while it is not expressed in bile duct cancer
      accompanied by PBM.

PMID- 15161012
TI  - Relationship between differentiation-inducing activity and hypercalcemic activity
      of hexafluorotrihydroxyvitamin D3 derivatives.
AB  - Among 16 newly synthesized hexafluorotrihydroxyvitamin D3 derivatives, 24-Homo
      26,26,26,27,27,27-hexafluoro (24H-F6)-1,24(S), 25(OH)3 vitamin D3 (VD3) (DD-011)
      [16] induced differentiation (i.e., appearance of NBT-positive cells) of human
      promyelocytic leukemic HL-60 cells most efficiently (EC50=0.5 nM), followed by
      24H-F6-1,25(OH)2-22-oxa-VD3 (DD-006) [11] > F6-1,25(OH)2-VD3 (F6VD3) [2] > F6
      1,25(OH)2-22-ene-VD3 (DD-009) [14] > 24H-F6-1,25(OH)2-VD3 (F6C28) [3] > 24H-F6
      1,25(OH)2-1,23(S),25(OH)3-VD3 (DD-015) [18] > 24H-F6-1,25(OH)2-22-ene-VD3
      (mvd1400) [6] > 22H-F6-1,25(OH)2-24-ene-VD3 (mvd3400) [5] > 24H-F6
      1,23(R),25(OH)3-VD3 (DD-014) [17] > 24H-F6-1,22(S),25(OH)3-VD3 (DD-003) [7] > 24H
      F6-1,22(S),25(OH)3-24-yne-VD3 (DD-005) [9] > 24H-F6-1,22(R),25(OH)3-24-yne-VD3
      (mvd-1235) [10] > F6-1,25(OH)2-22-ene-VD3 (DD-008) [13] = 1,25(OH)2VD3 [1]
      (CC50=6 nM). On the other hand, 24H-F6-1,22(R),25(OH)3-VD3 (DD-004) [8], which is
      an isomer of DD-003 [7], showed much reduced activity (CC50=100 nM), suggesting
      the importance of the configuration of the OH group at the C-22. When their
      differentiation-inducing activity was plotted vs. the octanol-water partition
      coefficient (log P) used as a parameter of hydrophobicity, a bell-shaped curve
      was produced, with the bottom at log P=5.4-5.8. There was no clear-cut
      relationship between the differentiation-inducing activity and hypercalcemic
      activity (serum calcium elevating activity). Compounds [3, 7, 11, 17] showed
      relatively higher differentiation-inducing activity, with lesser hypercalcemic
      activity, as compared with [1]. Administration of [7] showed potent
      antiproliferation activity against colon cancer transplanted in nude mice. These
      results further confirmed the antitumor potential of hexafluorotrihydroxyvitamin
      D3 derivatives.

PMID- 15161013
TI  - CD40 ligand stimulation inhibits the proliferation of mantle cell lymphoma lines.
AB  - Mantle cell lymphoma (MCL) is a CD5+ non-Hodgkin's B-cell lymphoma characterized
      by the infiltration of intermediate sized B-cells into the mantle zones.
      Interaction between CD40L and CD40 is important for B cell proliferation and
      differentiation. CD40L stimulation can induce both growth arrest and
      proliferation of B cell lines according to their differentiation state. Previous
      reports examining the effect of stimulation via the CD40 cascade on ex vivo MCL
      cells have provided conflicting results. In this study, two MCL lines, SP49 and
      SP53, were examined for response to CD40L and/or IL-10. Co-cultivation with CD40L
      expressing mouse L cells reduced the BrdU incorporation of SP49 and SP53 cells by
      half to one-third, while BrdU incorporation of control cell lines, including
      Ramos, BJAB and BALL-1, was not affected or increased. Anti-CD40L antibody
      blocked the CD40L inhibition of SP49 cell proliferation in a dose-dependent
      manner in the range from 0 to 20 ng/ml. IL-10 did not affect MCL cell
      proliferation in the presence or absence of CD40L-expressing cells, while Ramos
      proliferation was promoted by CD40L and IL-10. These results suggested the
      possibility that CD40L may also inhibit MCL proliferation in vivo.

PMID- 15161015
TI  - Expression pattern of the HMGB1 gene in sarcomas of the dog.
AB  - BACKGROUND: The human high mobility group protein B1 (HMGB1) has attracted
      considerable interest among oncologists because it sensitises cancer cells to the
      anticancer drug cisplatin by shielding cisplatin-DNA adducts from nucleotide
      excision repair. MATERIALS AND METHODS: Since cisplatin is the cornerstone of
      adjuvant systemic therapy for osteosarcomas, in both humans and dogs, the
      expression pattern of the HMGB1 gene in seven canine sarcomas was investigated by
      Northern blot analysis and semi-quantitative RT-PCR. RESULTS: A strong
      intertumoural variation of HMGB1 expression was detected by Northern blot
      analysis and confirmed by the semi-quantitative RT-PCR established herein.
      CONCLUSION: The observed variations of HMGB1 expression in canine sarcomas
      emphasises the role of HMGB1 as a potential marker of clinical interest as its
      expression level may predict the clinical outcome of therapies based on
      cisplatin. The semi-quantitative RT-PCR established allows a quick and convenient
      determination of the HMGB1 expression level as necessary for clinical
      applications.

PMID- 15161014
TI  - Increased tyrosine kinase activites may lead to the phenotypic differences of
      gastric cancer cells.
AB  - BACKGROUND: The aim of this study was to elucidate possible mechanisms
      responsible for the phenotypic difference in gastric cancer cells between the
      intestinal type and the diffuse type. MATERIALS AND METHODS: The gastric cancer
      cell lines MKN7 and KATO-III were used. Expression of adhesion molecules and
      protein tyrosine phosphorylation were examined by immunoblotting. Protein-protein
      interactions were determined by immunoblotting following immunoprecipitation. ERK
      activity was assessed by immunoblotting using anti-phospho-ERK antibody. RESULTS:
      E-cadherin expression in KATO-III was decreased compared to that in MKN7. The
      expression of alpha-, beta- and gamma-catenin was not significantly different;
      beta- and gamma-catenin were highly tyrosine phosphorylated in KATO-III but not
      in MKN7. In KATO-III, a number of tyrosine phosphorylated proteins, including
      extracellular signal-regulated protein kinases (ERKs) and epidermal growth factor
      receptor (EGFR), were observed irrespective of EGF stimulation and induction of
      ERK activity and EGFR tyrosine phosphorylation by EGF were less than that in
      MKN7. CONCLUSION: Increased tyrosine kinase activities may cause diminished
      expression of E-cadherin and tyrosine phosphorylation of catenins, resulting in
      the abrogated cell-cell adhesion in gastric cancer cells.

PMID- 15161016
TI  - Induction of apoptosis by beta-diketones in human tumor cells.
AB  - A variety of beta-diketones were evaluated for their cytotoxic profiles against
      oral human normal and tumor cells. Among 22 compounds (BD1-22) tested, the
      cytotoxicity of 3-formylchromone (BD17) (CC50=7.8 microg/mL) against human oral
      squamous cell carcinoma (HSC-2) cells was higher than that of curcumin (CC50=23.6
      microg/mL). Tumor cell-specific cytotoxicity was also detected in BD17 which
      exhibited little cytotoxic activity against a normal human cell, gingival
      fibroblast (HGF). (-)-3- (BD13) (CC50=21.7 microg/mL) and (+)-3
      (Trifluoroacetyl)camphor (BD12) (CC50=29.7 microg/mL) are enantiomers and showed
      cytotoxicity comparable to curcumin and dibenzoylmethane (BD2) (CC50=22.5
      microg/mL). BD13 did not induce DNA fragmentation in HL-60 cells nor activate
      caspase 3, 8 and 9 in both HL-60 and HSC-2 cells, regardless of the presence or
      absence of FeCl3. On the other hand, BD17 was found to induce apoptosis in HSC-2
      and HL-60 cells, as judged by internucleosomal DNA fragmentation, caspase 3, 8
      and 9 activation and dysfunction of mitochondrial membrane potential. The
      cytotoxic activity of BD13, BD17 and curcumin was significantly reduced by
      chelation with FeCl3. The tumor-specific cytotoxicity and apoptosis-inducing
      activity of BD17 against human tumor cells undoubtedly warrant further studies of
      its efficacy as a cancer chemotherapeutic agent.

PMID- 15161017
TI  - Green fluorescent protein expression and visualization of mediastinal lymph node
      metastasis of human lung cancer cell line using orthotopic implantation.
AB  - BACKGROUND: Suppression of lymphatic metastasis improves survival in lung cancer
      patients. We have reported a patient-like model of lung cancer metastasis based
      on orthotopic implantation in severe combined immunodeficiency (SCID) mice and
      demonstrated the lymphogenous spread histologically using human NSCLC cell lines.
      MATERIALS AND METHODS: To visualize micrometastases, we transfected the Aequorea
      Victoria jellyfish green fluorescent protein (GFP) gene to the cancer cell line.
      RESULTS: The tumor cell lines were able to stably express GFP at high levels both
      in vitro and in vivo. Fluorescent tumors and metastasis of the mediastinum could
      be visualized at microscopic levels after transplantation. CONCLUSION: This model
      demonstrated that GFP gene-transfected tumor cells represent a new tool for
      evaluating the metastatic process and are very useful for developing chemotherapy
      to inhibit metastasis.

PMID- 15161018
TI  - Fluorescence-based assessment of LRP activity: a comparative study.
AB  - BACKGROUND: Broad resistance to anticancer drugs is a major cause of failure in
      cancer treatment. The Lung Resistance-related Protein (LRP) is a protein
      associated with drug resistance, which is involved in nucleo-cytoplasmic
      transport and is known to predict a poor response to chemotherapy in acute
      myeloid leukaemia. The only method allowing the detection of LRP activity is
      based on radio-labelled daunorubicin incorporation. Our goal was to develop a
      fluorescence-based assay to analyse LRP function. MATERIALS AND METHODS: We used
      human colon carcinoma cell lines treated with sodium butyrate (NaB) in order to
      induce LRP expression. Daunorubicin efflux in isolated nuclei was measured by
      flow cytometry, the localization and quantification of Daunorubicin analysed by
      confocal laser scanning microscopy (CLSM) and the diffusion coefficient of this
      drug estimated by Fluorescence Correlation Spectrometry (FCS). RESULTS: According
      to the method using [14C] Doxorubicin cells incubated with NaB displayed an
      efflux of Daunorubicin out of isolated nuclei demonstrated by flow cytometry or
      CLSM. The FCS method was able to evaluate kinetics of Daunorubicin molecules in
      nucleus and cytoplasm and showed a higher dispersion of Daunorubicin kinetics
      with cells previously NaB-treated. This argument is in favour of an increase of
      nucleo-cytoplasmic exchange. CONCLUSION: Using CLSM we showed that LRP was able
      to modify anticancer drug repartition in the cells. LRP activity assessment needs
      either isolated nuclei if flow cytometry is employed, or FCS, and only a few
      cells may be analysed.

PMID- 15161019
TI  - Antitumor effects of lipoxygenase inhibitors on murine bladder cancer cell line
      (MBT-2).
AB  - Arachidonic acid (AA) metabolites derived from both the lipoxygenase (LOX) and
      cyclooxygenase (COX) pathways transduce a variety of signals related to cell
      growth. Selective blockade of the different metabolic pathways of AA (using a
      general LOX inhibitor NDGA, a 5-LOX inhibitor AA861, a 12-LOX inhibitor baicalein
      and a general COX inhibitor ibuprofen) revealed that murine bladder cancer cell
      line (MBT-2) cell proliferation was inhibited by the LOX inhibitors concentration
      dependently, but not by the COX inhibitor. Among the LOX inhibitors, baicalein
      showed the strongest inhibition and induced apoptosis of MBT-2. Proliferation of
      MBT-2 was also significantly inhibited by 12-LOX antisense oligonucleotides. In
      an in vivo experiment, the antitumor effects of baicalein administration on
      C3H/HeN mice implanted with MBT-2 were recognized. These results suggested that
      LOX inhibition may be significant in the treatment of bladder cancer.

PMID- 15161020
TI  - Structure-activity relationships of alpha, beta-unsaturated ketones as assessed
      by their cytotoxicity against oral tumor cells.
AB  - A series of simple alpha, beta-unsaturated carbonyl compounds (1-26) was
      characterized for their cytotoxic profiles against oral human normal and tumor
      cells. Several cycloalkenones showed potent cytotoxic activities against human
      oral squamous cell carcinoma HSC-2 cell line. Among them, 4,4-dimethyl-2
      cyclopenten-1-one (12) exhibited low cytotoxic activity against a normal human
      cell, gingival fibroblast HGF, and displayed higher tumor-specific cytotoxicity
      (SI value = CC50 (HGF)/CC50 (HSC-2) = 4.0). The cytotoxicities of the unsaturated
      lactones were moderately tumor-specific (SI = 1.5-1.9). Agarose gel
      electrophoresis showed that the induction of internucleosomal DNA fragmentation
      in human promyelocytic leukemia cell HL-60 is dependent on the structure of
      alpha, beta-unsaturated carbonyl compounds. Fluorometric protease assay showed
      that some, but not all compounds, activated the caspase 3 in a dose-dependent
      manner. All alpha, beta-unsaturated carbonyl compounds studied did not activate
      caspases 8 and 9. The cytotoxic activity of alpha, beta-unsaturated carbonyl
      compounds was profoundly reduced in the presence of N-acetylcysteine. The study
      suggests that the presence of a non sterically hindered Michael acceptor seems to
      be an essential structural requirement for the cytotoxic activity in alpha, beta
      unsaturated ketones.

PMID- 15161021
TI  - Plant phenolics protect from bleomycin-induced oxidative stress and mutagenicity
      in Salmonella typhimurium TA102.
AB  - Antioxidants are deemed to be important against DNA damage and mutations induced
      by reactive oxygen species (ROS). An assay for the ability of plant phenolics to
      protect against mutations caused by bleomycin treatment in Salmonella typhimurium
      TA102 cells in concentrations up to 20 microM was developed. Caffeic acid, gallic
      acid, protocatechuic acid, ferulic acid and rutin hydrate in final concentrations
      of 0.5 to 20 microM were tested for their ability to protect TA102 cells from
      mutations caused by oxidative stress from bleomycin. The cut-off concentration of
      20 microM was used because as a limit it is biologically meaningful, higher
      concentrations being unrealistic in vivo. Caffeic acid was very potent at a
      concentration of 0.5-20 microM. The other four antioxidants were not effective up
      to 20 microM. The above assay will be helpful to characterize antioxidant
      molecules.

PMID- 15161022
TI  - EGCG blocks tumor promoter-induced MMP-9 expression via suppression of MAPK and
      AP-1 activation in human gastric AGS cells.
AB  - Overexpression of matrix metalloproteinases (MMPs) has been known to correlate
      closely with tumor cell invasion and strategies to down-regulate their expression
      may ultimately be of clinical utility. In this study, we investigated the effects
      of (-)-epigallocatechin gallate (EGCG), a major green tea catechin, on the cell
      invasiveness and MMP-9 induction in human gastric cancer AGS cells. EGCG
      inhibited the phorbol 12-myristate 13-acetate (PMA)-induced cell invasiveness and
      MMP-9 expression in a dose-dependent manner. EGCG treatment was found to reduce
      the MMP-9 transcriptional activity. To further study the mechanisms for the EGCG
      mediated regulation of MMP-9, the effects of EGCG on transcription factor AP-1
      and mitogen-activated protein kinase (MAPK) activities were examined. The results
      showed that EGCG suppressed the PMA-induced AP-1 activation. EGCG also abrogated
      the PMA-induced activation of extracellular-regulated protein kinase (Erk) and c
      jun N-terminal kinase (JNK), which are upstream modulators of AP-1. These results
      suggest that EGCG may exert at least part of its anti-invasive effect in gastric
      cancer by controlling MMP expression through the suppression of MAPK and AP-1
      activation.

PMID- 15161023
TI  - Cytotoxic activity of deferiprone, maltol and related hydroxyketones against
      human tumor cell lines.
AB  - Hydroxyketone chelators, deferiprone (HK1), maltol (HK3) and their related
      compounds (HK2, 4-8), were characterized for their cytotoxic profiles against
      oral human normal and tumor cells. Most hydroxyketones except HK6 showed
      relatively higher tumor-specific cytotoxicity. Deferiprone (HK1), which showed
      the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3)
      in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma
      HSC-2 cell lines. The cytotoxic activity of HK1 against HL-60 and HSC-2 cells was
      reduced in the presence of FeCl3, while that of HK3 was significantly increased
      by FeCl3. Agarose gel electrophoresis showed that HK1 induced internucleosomal
      DNA fragmentation in HL-60 cells, but the addition of FeCl3 inhibited the DNA
      fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of
      the presence or absence of FeCl3. In HSC-2 cells, HK1 and 3 did not induce DNA
      fragmentation in the presence or absence of FeCl3. Colorimetric protease assay
      showed that HK1 activated the caspase 3, 8 and 9 in HL-60 cells. On the other
      hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated
      the caspase 3 only slightly in the presence of FeCl3. HK1 and 3 also activated
      the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study
      suggested that the antitumor activity of hydroxyketones may be modified by Fe3+
      concentration.

PMID- 15161024
TI  - Cytotoxicity and cell death pathways invoked by two new rhodium-ferrocene
      complexes in benign and malignant prostatic cell lines.
AB  - BACKGROUND: Apoptotic propensity is currently viewed as an important parameter in
      drug-induced toxicity. But other cell death pathways exist e.g. micronucleation,
      intermitotic cell death, abnormal nuclear morphology and necrosis. This
      investigation explores the onset of apoptosis and abnormal morphology in response
      to 3 drugs i.e. Cisplatin, a novel Ferrocene (fctfa) and a novel Rhodium
      Ferrocene [Rh(fctfa)(cod)] complex. MATERIALS AND METHODS: A pair of prostate
      cell lines from normal human prostate epithelium (1542N) and malignant human
      prostate epithelium (1542T) were exposed to increasing concentrations of the
      drugs for 24 hours, double-stained with FITC-Annexin V and with Propidium Iodide
      and analysed by dual parameter flow cytometry to quantitate viable cells in
      quadrant I, early apoptotic cells in quadrant IV and late apoptotic/necrotic
      cells in quadrant III. Apoptosis was also scored by microscopy after Acridine
      Orange staining, by Western blots for caspase 3 induction and for caspase 8
      induction using a colorimetric assay. RESULTS: The toxicity of Cisplatin and the
      Ferrocene and Rhodium-Ferrocene complexes was found to be 0.9-1.3 microM; 4.1-4.5
      microM and 10.1-13.2 microM, respectively. Apoptotic propensity scored after 24
      hours was found to be dose-dependent and in the range of 7-19% for Cisplatin and
      1-4.1% for the Ferrocene and Rhodium-Ferrocene complexes. Cisplatin produces a
      distinct apoptotic response followed by a necrotic response, whereas the
      Ferrocene and the Rhodium-Ferrocene complexes produce a massive necrotic reaction
      in the region of 3-19% and very little if any apoptosis. Absence of apoptosis was
      corroborated by lack of caspase 3 activation, absence of typical apoptotic
      morphology and by lack of caspase 8 activation. CONCLUSION: The 3 drugs
      Cisplatin, the novel Ferrocene and the novel Rhodium-Ferrocene complexes show
      similar toxicities in the 1-10 micro-molar range in prostate cell lines. However
      the drugs differ significantly in the activation of death pathways. While
      Cisplatin predominantly induces apoptosis documented by morphology, Annexin V
      staining and caspase 8 activation, the Ferrocene and Rhodium-Ferrocene complexes
      induce late necrosis and abnormal nuclear morphology. Unlike Cisplatin-treated
      cells which enter apoptosis and necrosis sequentially, the 2 Ferrocene drugs
      invoke direct entry of cells into late necrosis without first entering the early
      apoptotic compartment.

PMID- 15161025
TI  - Cytokeratin 17 and p63 are markers of the HPV target cell, the cervical stem
      cell.
AB  - BACKGROUND: Basic research on HPV has focused on identifying the genetic changes
      that lead to cervical carcinoma. However, while focusing on the molecular biology
      of the cancer, understanding of its cellular biology has lagged: the target cell
      of the HPV infection is unknown. MATERIALS AND METHODS: In this study we
      identified the stem cell population of the cervical epithelium by monoclonal
      antibodies against p63, a homologue of the tumor suppressor gene p53 and
      cytokeratin 17 (CK17). RESULTS: We noted p63 expression consistently in the
      nuclei of reserve cells, hyperplasia of the reserve cells and the basal layer of
      the ectocervical epithelium, while CK17 only stained endocervical reserve cells
      and reserve cell hyperplasia. CONCLUSION: We conclude that both p63 and CK17 are
      suitable markers for cervical stem cell identification. Both markers, therefore,
      qualify for the identification of the HPV target cell.

PMID- 15161026
TI  - Inverse correlation between expression levels of p27 and the ubiquitin ligase
      subunit Skp2 in early esophageal squamous cell carcinoma.
AB  - BACKGROUND: In esophageal squamous cell carcinoma (SCC), the relationship between
      expression of the cyclin-dependent kinase inhibitor p27 and tumor aggression and
      prognosis is still controversial. Moreover, the expression of S-phase kinase
      interacting protein 2 (Skp2), the ubiquitin ligase subunit required for the
      ubiquitin-dependent degradation of p27, remains unknown. MATERIALS AND METHODS:
      We used immunohistochemistry to analyze Skp2 and p27 expression in surgical
      specimens obtained from 32 patients with early esophageal SCC. We also used
      Western blotting to characterize the expression of Skp2 and p27 in 7 cell lines
      derived from esophageal SCC. RESULTS: Expression of Skp2 showed an inverse
      topographic distribution and correlation to that of p27 in many esophageal
      carcinomas. Of the 7 cell lines, 6 showed an inverse relationship between Skp2
      and p27 expression. Patients without an inverse correlation between Skp2 and p27
      expression had a significantly unfavorable prognosis in the early stage
      (p=0.0493). CONCLUSION: These findings suggest that the target substrate of Skp2
      in early esophageal SCC is mainly p27, and that failure of Skp2-induced
      degradation of p27 may influence tumor progression and lead to a poor prognosis.

PMID- 15161027
TI  - Lack of preventive efficacy of FK228, a histone deacetylase inhibitor, against N
      butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in
      p53+/- and p53+/+ mice.
AB  - BACKGROUND: The efficacy of FK228, a histone deacetylase inhibitor that is
      currently under early clinical trials for cancer therapy, against N-butyl-N-(4
      hydroxybutyl)- nitrosamine (BBN) -induced mouse urinary bladder carcinogenesis
      was examined. MATERIALS AND METHODS: Heterozygous p53-deficient (p53+/-) and wild
      type (p53+/+) mice were given FK228 (0, 0.01 and 0.1 mg/kg i.p., 3 times/week,
      respectively) after 10 weeks of 0.05% BBN treatment, and were sacrificed at 22
      and 24 weeks after the start, respectively. RESULTS: There was no significant
      difference in the incidence of urinary bladder tumors among groups in the p53+/-
      or p53+/+ mice, although the high dose of FK228 increased the p21WAF1 mRNA
      expression in urinary bladder cancers in animals of both genotypes. CONCLUSION:
      The present data indicate a lack of any inhibitory effects of FK228 on BBN
      induced mouse urinary bladder carcinogenesis under the present conditions.

PMID- 15161028
TI  - Variations of telomerase activity in cultured mouse fibroblasts upon
      proliferation of polyomavirus.
AB  - Telomerase plays a central role in various biological phenomena such as cell
      differentiation and proliferation, apoptosis, malignant transformation and virus
      infection, for instance HIV and papillomavirus. In addition, it has recently been
      shown that, in human fibroblasts transformed by monkey polyomavirus SV40,
      telomeres became stabilized as a consequence of telomerase activation. However,
      no information exists on the effects of acute infection by murine polyomavirus on
      the telomeres maintenance and telomerase activity in the host cell. In this paper
      we report on a differential activity of telomerase in productively infected
      cells. The results showed a decreased activity of the enzyme as assessed by the
      TRAP assay. The decrease had already occurred at a non-lytic time of infection
      and was observed both after infection and naked DNA transfection. Therefore
      nuclear decapsidation is not involved in the determination of the phenomenon that
      is attributed to the proliferation of the virus.

PMID- 15161029
TI  - Inhibitory effect of genistein and daidzein on ovarian cancer cell growth.
AB  - BACKGROUND: Survival from ovarian cancer has not changed significantly in the
      past twenty years requiring development of additional treatment protocols. We
      studied the effect of genistein and daidzein on ovarian cancer cell growth.
      MATERIALS AND METHODS: Five ovarian cancer cell lines from Stage IIIC disease
      were evaluated. Sulforhodamine B and colony formation assays were used to analyze
      growth inhibitory effects of genistein and daidzein alone and with cisplatin,
      paclitaxel or topotecan. Apoptosis induction was studied by determining caspase-3
      activity. RESULTS: Inhibition of growth (50-80%), colony formation and colony
      size was seen at 144 microm of genistein, 0-23% reduction was demonstrated at 9
      microm. At 144 microm, the colony size was inhibited >75%; at 9 microm 4/5 cell
      lines had >50% reduction. Caspase-3 activity was induced (0.10 to 0.56
      pmol/min/microg protein) with all concentrations of genistein. Cisplatin (2-50
      microg/ml) and topotecan (0.5-50.0 microm) combined with genistein resulted in a
      mostly additive effect, paclitaxel (8-200 nM) was slightly less than additive.
      CONCLUSION: We demonstrate an inhibitory effect of genistein on ovarian cancer
      cell growth.

PMID- 15161030
TI  - Glutamyl- but not aspartyl-aminopeptidase activity is modified in serum of N
      methyl nitrosourea-induced rat mammary tumours.
AB  - BACKGROUND: The rat model of breast cancer induced by the administration of N
      methyl-nitrosourea (NMU) constitutes a useful tool for dissecting the initiation,
      promotion and progression process of carcinogenesis. Angiogenesis, the
      recruitment of new blood vessels, is an essential component of the metastatic
      pathway. Tumour vessels have an aberrant response to constrictor hormones, such
      as angiotensin II (Ang II). Ang II degradation to form angiotensin III (Ang III)
      begins with the action of glutamyl aminopeptidase (GluAP) and aspartyl
      aminopeptidase (AspAP), named together as aminopeptidase A activity (APA). The
      present work analyses GluAP and AspAP activities in serum of NMU-induced rat
      mammary tumours, to evaluate the putative value of these activities as biological
      markers of the initiation and promotion of the disease. MATERIALS AND METHODS:
      Serum AspAP and GluAP activities were measured fluorimetrically using their
      corresponding aminoacyl-beta-naphthylamide. RESULTS: The increase found in GluAP
      but not in AspAP suggests an increase in Ang III and a decrease in Ang II serum
      circulating levels. CONCLUSION: The decrease in Ang III may be responsible for
      the overexpression of AT1 receptors described in breast cancer. However,
      increased levels of Ang III, which exhibit the same affinity for the AT1
      receptor, would favour the development of the disease.

PMID- 15161031
TI  - All-trans retinoic acid (ATRA) suppresses transcription of human papillomavirus
      type 16 (HPV16) in a dose-dependent manner.
AB  - Earlier we found that SiHa cervical squamous carcinoma cells that harbor HPV type
      16 respond to ATRA treatment in a dose-dependent manner: high-dose (10(-5)-10(-4)
      M) but not low-dose (10(-7)-10(-6) M) ATRA induced growth arrest. Growth of HPV
      infected cells is highly dependent on the expression of the viral E6/E7 proteins.
      Thus, targeting expression of the viral E6/E7 genes might influence growth
      properties of HPV-infected cells. Here, we demonstrated that high-dose ATRA
      inhibited expression of HPV16 E7 through suppression of the HPV16 promoter (p97)
      activity. Gelshift assay (EMSA) revealed that binding of the AP-1 transcription
      factor to an oligonucleotide originated from the HPV type 16 promoter was
      diminished after high-dose, but not low-dose ATRA treatment. This suggests that
      high-dose ATRA suppresses HPV 16 promoter activity, at least in part, via a
      decreased AP-1 binding. Our data might be useful in treatment of cervical
      dysplasias and/or carcinomas.

PMID- 15161033
TI  - Down-regulation of the human tumor antigen mucin by gemcitabine on the pancreatic
      cancer cell line capan-2.
AB  - The nucleoside analogue gemcitabine displays therapeutic effects mainly against
      breast, ovarian and pancreatic cancer. Mucin, encoded by the gene MUC1, is a well
      established tumor antigen expressed on these tumors. Knowledge of possible
      effects of chemotherapeutic drugs on the level of mucin epitope expression is
      important for the design of clinical protocols combining chemo- and
      immunotherapeutic approaches. In this study, we determined the influence of
      gemcitabine on the mucin expression of the human pancreatic carcinoma cell line
      Capan-2. The cells were treated with three different concentrations (0.01
      microg/ml, 0.1 microg/ml and 0.25 microg/ml) of gemcitabine or were left
      untreated and were analyzed after 24 hours, 3 and 5 days. Flow cytometric
      analysis showed a dose-dependent decrease of mucin expression on the cell surface
      which remained over 5 days. The strongest reduction of mucin expression was
      detectable 24 hours after application of the drug. The down-regulation of the
      tumor antigen mucin by gemcitabine might weaken an immune response against mucin
      expressing tumors, which are under treatment with this chemotherapeutic drug.

PMID- 15161032
TI  - Selective inhibition of survival signal transduction pathways enhanced
      radiosensitivity in human esophageal cancer cell lines in vitro.
AB  - PURPOSE: The purpose of this study was to examine how selective inhibition of the
      survival signal transduction pathways affects radiosensitivity in human cancer
      cell lines. MATERIALS AND METHODS: Two human esophageal cancer cell lines, TE-1
      (mutant p53) and TE2 (wild-type p53), were used. To inhibit the pathways
      selectively, 3 specific kinase inhibitors, AG1478 (an inhibitor of EGFR), PD98059
      (an inhibitor of MEK) and LY294002 (an inhibitor of PI3K), were combined with
      radiation. RESULTS: Radiation in combination with these kinase inhibitors
      potentiated radiation-induced cell killing synergistically. Enhancement ratios
      were greater in TE-2 than those in TE-1. Radiation in combination with kinase
      inhibitors increased the expression of the active form of caspase-3 and the PARP
      cleavage only in TE-2 that has wild-type p53. CONCLUSION: Targeting the key
      molecules of the survival signal transduction pathway resulted in potentiation of
      radiation-induced cell killing. The results of this study suggest that the
      survival signal transduction pathways would be a molecular target in enhancing
      radiosensitivity.

PMID- 15161035
TI  - Effect of octreotide on apoptosis-related proteins in rat Kupffer cells: a
      possible anti-tumour mechanism.
AB  - BACKGROUND: Octreotide may prolong survival in patients with hepatocellular
      carcinoma, through an as yet unidentified mechanism. Kupffer cells play a key
      role in antitumour activity. Kupffer cell apoptosis is of major importance for
      the maintenance of this antitumour activity. MATERIALS AND METHODS: We studied
      the in vitro effects of octreotide in the RNA expression of apoptotic and
      antiapoptotic proteins in isolated rat Kupffer cells, before and after exposure
      to lipopolysaccharide (LPS). Apoptotic and antiapoptotic gene expression was
      assessed using a semi-quantitative multiplex RT-PCR measuring bax, bcl-xS, bcl-2
      and bcl-xL. LICE (caspase-3) mRNA was used as a measure of apoptosis. RESULTS:
      Unstimulated Kupffer cells exhibited increased proapoptotic gene expression in a
      time-dependent manner, paralleled by a similar increase of LICE. LPS stimulation
      decreased the expression of proapoptotic bax and bcl-xS mRNA without effecting
      the antiapoptotic proteins. A decrease of LICE expression became significant at
      48 hours. Octreotide showed a reduction of proapoptotic proteins, accompanied by
      an early increase and a late reduction of antiapoptotic proteins and a net
      decrease of LICE expression. A combination of LPS and octreotide produced a
      similar effect with the exception of a late increase of LICE expression, probably
      caused by a late increase of bax and bcl-xS. CONCLUSION: LPS and octreotide
      reverse the observed increased apoptosis of cultured Kupffer cells by influencing
      both proapoptotic and antiapoptotic proteins. Therefore, the antitumour effect of
      octreotide in hepatocellular carcinoma may, in part, be explained by its
      antiapoptotic effect on Kupffer cells.

PMID- 15161034
TI  - Resistance developing after long-term ganciclovir prodrug treatment in a
      preclinical model of NSCLC.
AB  - BACKGROUND: We recently demonstrated a 100% increase in the survival period with
      ganciclovir (GCV) therapy in mice hearing orthotopic HSV-TK-positive non-small
      cell lung cancer (NSCLC) tumors. However, long-term survival was not achieved.
      The aim of the present study was to evaluate tumor growth during extended GCV
      therapy and to monitor the herpes simplex virus thymidine kinase (HSV-TK) gene
      and protein in tumors at different time points. MATERIALS AND METHODS: The human
      NSCLC cell line KNS 62 was retrovirally transduced with the HSV-TK30 gene. Cell
      suspensions in which 100% or 25% of the cells were TK30-positive were inoculated
      subcutaneously in SCID bg mice. Tumor growth was evaluated during GCV therapy and
      HSV-TK DNA, RNA and protein were analyzed at different time points using PCR, RT
      PCR and immunoblotting. RESULTS: HSV-TK DNA, RNA and TK30 protein were
      demonstrated in the tumors 21 days after subcutaneous tumor inoculation. TK
      positive tumors regressed during GCV therapy and tumors in which 25% of the cells
      were TK-positive grew significantly more slowly than control tumors did. After 4
      weeks of GCV therapy, HSV-TK DNA, RNA and TK protein were not detectable in the
      remaining tumors, which were therefore resistant to further GCV therapy.
      CONCLUSION: Prodrug therapy of the NSCLC cell line KNS 62, including bystander
      effects, is sufficient. Nevertheless, GCV-resistant tumors develop after
      functional loss of the TK gene. In the clinical context, further studies will
      need to evaluate immunological bystander effects or combinations with other
      drugs.

PMID- 15161036
TI  - Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on
      rat gastrointestinal UDP-glucuronosyltransferases.
AB  - BACKGROUND: Dietary compounds or nonsteroidal anti-inflammatory drugs (NSAIDs)
      may reduce cancer rates. Elevation of phase II detoxification enzymes might be
      one of the mechanisms leading to cancer prevention. We investigated the effects
      of dietary anticarcinogens and NSAIDs on rat gastrointestinal UDP
      glucuronosyltransferases (UGT). MATERIALS AND METHODS: Diets of Wistar rats were
      supplemented with oltipraz, alpha-tocopherol, beta-carotene,
      phenethylisothiocyanate (PEITC), sulforaphane analogue compound-30, indole-3
      carbinol, D-limonene, relafen, indomethacin, ibuprofen, piroxicam, acetyl
      salicylic acid or sulindac. Hepatic and intestinal UGT enzyme activities were
      quantified by using 4-nitrophenol and 4-methylumbelliferone as substrates.
      RESULTS: Compound-30, D-limonene, indomethacin, ibuprofen or sulindac enhanced
      proximal small intestinal UGT activities. Only compound-30 was able to induce mid
      and distal small intestinal UGT activities. Large intestinal UGT activities were
      increased by ibuprofen and sulindac, whereas oltipraz, PEITC and D-limonene gave
      enhanced hepatic UGT activities. CONCLUSION: Mainly rat proximal small intestinal
      and hepatic UGT enzyme activities were induced by dietary anticarcinogens or
      NSAIDs. Enhanced UGT activities might lead to a more efficient detoxification of
      carcinogenic compounds and thus could contribute to the prevention of
      gastrointestinal cancer.

PMID- 15161038
TI  - Effect of cycloartanes on reversal of multidrug resistance and apoptosis
      induction on mouse lymphoma cells.
AB  - The ability of fifteen cycloartanes, isolated from Euphorbia species, to reverse
      multidrug resistance (MDR) and apoptosis induction in L5178Y mouse lymphoma
      cells, including its multidrug-resistant subline, was studied by flow cytometry.
      Reversion of MDR was investigated using a standard functional assay with
      rhodamine 123 as a fluorescent substrate analogue. For the evaluation of
      apoptosis, the cells were stained with FITC-labeled annexin V and propidium
      iodide. The majority of the compounds were able to reverse MDR of the tested
      human MDR1 gene-transfected mouse lymphoma cells. Some of the compounds were able
      to induce moderate apoptosis in the PAR cell line, but this effect was less
      effective on multidrug-resistant cells. The results indicate that cycloartanes
      can be substrates of ABC transporters, which might compete with certain
      anticancer chemotherapeutics.

PMID- 15161037
TI  - Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated
      apoptosis.
AB  - BACKGROUND: The T-cell lymphoma cell line HuT78B1, selected for resistance to Fas
      mediated apoptosis, resulted unexpectedly resistant to the apoptotic and
      cytotoxic effects of gemcitabine (dFdC). We investigated whether this resistance
      was due to the impairment of the Fas/Fas-ligand (FasL) system. MATERIALS AND
      METHODS: dFdC effects were studied in HuT78B1 and in the parental Fas-sensitive
      HuT78 cells exposed to inhibitors of the Fas/FasL system. RESULTS: FasL- and Fas
      blocking antibodies did not interfere with dFdC-induced apoptosis in HuT78 cells,
      whereas inhibitors of caspase-8, -9, -1 or -3 had partial inhibitory effects.
      Notably, in HuT78B1 cells there was a markedly reduced dFdC accumulation
      notwithstanding a high activity of the activating enzyme deoxycytidine kinase.
      dFdC accumulation in HuT78 cells was unaffected by a Fas-blocking antibody.
      CONCLUSION: This is the first time that the selection of a Fas-resistant cell
      line led to the isolation of a cell clone unable to accumulate the deoxycytidine
      analog dFdC. Our results show that this alteration is independent from the
      impairment of the Fas/FasL system.

PMID- 15161039
TI  - New silicon compounds as resistance modifiers against multidrug-resistant cancer
      cells.
AB  - The efficiency of chemotherapy is often decreased by the development of
      resistance of cancer cells to cytostatic drugs. This phenomenon is in most cases
      caused by the activity of the various ABC transporters, multidrug-resistance
      (MDR) gene-encoded p-glycoproteins, that pump anticancer drugs out of the cells.
      The inhibition of the activities of the MDR proteins MDR1 and MRP was
      investigated via the administration of two new organosilicon compounds, alis-409
      and alis-421. The study was focused on the inhibition of MDR by blocking the ADR1
      gene expression and through the inhibition of the pump-function of mdr-p
      glycoprotein, in human breast cancer cell lines expressing mrp and prostate
      cancer cell line (PC-3). Apoptosis induction and the interaction between
      epirubicin and the silicon-substituted compounds were studied in human MDR-1 gene
      transfected mouse lymphoma and its parent cell line, Colo320/MDR-LRP and
      sensitive subline Colo205, by means of rhodamine 123 accumulation. The activity
      of MRP1 p-glycoprotein was studied in human breast cancer cell lines such as HTB
      26/MRP1 and two MRP-negative breast cancer cell lines, T47D and MCF7, by
      carboxyfluorescein accumulation, and on a stomach cancer cell line. The activity
      of MRP in 257P/MDR and its drug-sensitive derivative were studied in human
      stomach cancer cells by daunorubicin accumulation in a flow cytometer. The two
      representative organosilicon derivatives, alis-409 and alis-421, showed
      antiproliferative effects without apoptosis induction. The drug accumulation in
      the human MDR1 gene-transfected mouse lymphoma cells was increased without down
      regulation of the MDR1 gene expression tested by RT-PCR assay. The rhodamine
      uptake was increased in L5178/MDR1 and Colo320/MDR1-LRP, but not drug-sensitive
      human breast cancer MCF-7 and T47D, and L5178 mouse lymphoma parent cells in the
      presence of alis-409 and alis-421. The MRP-mediated carboxyfluorescein
      accumulation in HTB-26/MRP human breast cancer cells and daunorubicin
      accumulation in human stomach cancer cells 257P/MDR were not modified by these
      alis compounds. A synergistic interaction between epirubicin and the silicon
      substituted resistance modifiers was found only in MDR1-mediated MDR in the case
      of colo-320/MDR1-LRP cells and mouse lymphoma cells transfected with the human
      MDR1 gene. The results indicate that the organosilyl derivatives specifically act
      on MDR1 p-glycoprotein 170. The alis compounds act on pgp170 in a way which is
      similar to verapamil isomers.

PMID- 15161040
TI  - Induction of apoptosis and G2/M arrest by 2-methoxyestradiol in human cervical
      cancer HeLaS3 cells.
AB  - BACKGROUND: It has been demonstrated that 2-Methoxyestradiol (2-ME), one of the
      estrogen metabolites, induces apoptosis in many different tumor cell lines. In
      the present study, the effects of 2-ME on human cervical cancer HeLaS3 cells and
      on normal cervical epithelial cells were evaluated. MATERIALS AND METHODS:
      Acridine orange staining, DNA fragmentation arrays and flow cytometry were used
      to measure the apoptosis and cell cycle progression. In addition, the effect of 2
      ME on expression of iNOS was measured by Western blot. RESULTS: 2-ME inhibited
      the growth of HeLaS3 cells. This growth inhibition was accompanied by apoptosis
      and G2/M cell cycle arrest. 2-ME increased the expression of iNOS in parallel
      with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. 2
      ME treatment resulted in a slight increase of the G2/M population, but no
      apoptosis, in normal cervical epithelial cells. There was no synergetic effect
      between E2 and 2-ME. CONCLUSION: 2-ME induced apoptosis via the iNOS pathway and
      caused G2/M cell cycle arrest in human cervical cancer HeLaS3 cells, but showed
      only slight effects on normal cervical epithelial cells. These data suggest that
      2-ME might be an adjuvant agent in the treatment of cervical cancer.

PMID- 15161041
TI  - Overexpression of Id-1 in gastric adenocarcinoma: implication for a novel
      diagnostic marker.
AB  - Gastric cancer is the second most common cause of cancer-related death worldwide
      and the highest incidence of this cancer has been reported in Asia, especially in
      China. Identification of early stage lesions is vital in achieving high survival
      rate. However, due to the lack of reliable biomarkers, the majority of gastric
      cancer is presented at an advanced stage. Recently, it has been reported that Id
      1, a helix-loop-helix protein, may be a valuable diagnostic marker in many types
      of human cancer. In this study, we evaluated Id-1 protein expression in gastric
      cancer specimens and compared it with non-malignant tissues. In addition, to
      investigate whether Id-1 expression levels were associated with the
      aggressiveness of this disease as implicated in other cancer types, we also
      assessed Id-1 expression levels in primary tumours and their lymph node
      metastasized lesions. Our results indicate that up-regulation of Id-1 is a
      frequent event in gastric cancer but its expression levels are not associated
      with tumour metastasis. Our evidence provides a possible novel marker for the
      diagnosis of gastric cancer.

PMID- 15161042
TI  - Antitumour effects of a bispecific trivalent antibody in multicellular tumour
      spheroids.
AB  - BACKGROUND: New adjuvant immunological therapies that selectively redirect
      effector cells towards tumour cells are currently under development. These
      strategies include the use of bispecific antibodies as promising tools for the
      elimination of disseminated tumour cells and micrometastases. At present,
      bispecific molecules have demonstrated their antitumour potential in
      investigations in vitro using monolayer cell cultures. However, their
      effectiveness in vivo is less clear and expressive in vitro tumour models are in
      high demand. MATERIALS AND METHODS: Three-dimensional multicellular tumour
      spheroids (MTS) are of intermediate complexity between monolayer cell cultures
      and solid tumours in patients and therefore represent a particularly promising in
      vitro system. RESULTS: We show, here, the antitumour potential of a bispecific
      antibody, BiUII, in three-dimensional multicellular tumour spheroids and
      furthermore demonstrate that BiUII triggers peripheral blood mononuclear cells to
      invade MTSs and elicit the production of TNFalpha, resulting in the efficient
      destruction of tumour cells. CONCLUSION: These results demonstrate that
      bispecific antibodies are capable of activating immune effector cells, resulting
      in the elimination of three-dimensional structures of tumour cells. The
      therapeutic potential of these antibodies in the clinical setting merits further
      investigations.

PMID- 15161043
TI  - Serum HER-2/neu as a prediction and monitoring parameter in a phase II study with
      weekly paclitaxel in metastatic breast cancer.
AB  - Elevated levels of the extracellular domain of HER-2/neu in serum (sHER-2/neu)
      have been shown to be of prognostic importance. In this phase II study with
      weekly paclitaxel in metastatic breast cancer, we investigated the predictive
      quality of this serum oncoprotein by correlating the outcome of therapy to sHER
      2/neu levels. Paclitaxel (90 mg/m2 weekly x6, q9w) was administered to 35
      patients with complete outcome assessment and biochemical follow-up. sHER-2/neu
      was measured using standardized enzyme-linked immunoassays. We found that 62.9%
      (22/35) of the patients had elevated levels (> or = 15 ng/ml) of sHER-2/neu. The
      overall response rate (RR) to weekly paclitaxel was 40.0% (14/35). There was no
      difference in RR between sHER-2/neu-positive patients (40.9%) and sHER-2/neu
      negative patients (38.5%; p = 0.4). The progression-free interval was longer for
      sHER-2/neu-negative patients (53.2 weeks) in comparison to sHER-2/neu-positive
      patients (31.2 weeks; p = 0.098). Responses were significantly more durable in
      sHER-2/neu-negative patients (65.2 weeks) than in the sHER-2/neu-positive
      subgroup (25.7 weeks; p = 0.042). Introducing hypothetical cut-offs into the sHER
      2/neu-positive subset, we found that in patients with a sHER-2/neu level of
      greater than 22 ng/ml, the progression-free survival decreased significantly with
      increasing sHER-2/neu levels (p < or = 0.022). Considering the high impact of
      progression-free survival and duration of response as outcome parameters, the
      sHER-2/neu status is a predictive indicator for benefit from paclitaxel
      chemotherapy.

PMID- 15161044
TI  - Antitumor activity of imidazothioxanthones in murine and human tumor models in
      vitro and in vivo.
AB  - BACKGROUND: A new series of imidazothioxanthones has recently been synthesized as
      potential anticancer agents with the aim of overcoming drug resistance. The route
      of synthesis and DNA-binding properties of the compounds were reported
      previously. This paper describes the general structure-activity relationships for
      the class of imidazothioxanthones in panels of human and murine tumor cell lines
      in vitro, and the in vivo activity against human and murine solid tumors of the
      most potent compound, N-[3-(Dimethylamino)propylo]-11-oxo-11H-benzothiopyrano
      [3',2':2,3]pyrido[1,2-a]imidazo-2-carboxamide (10a). In addition, the interaction
      between compound 10a and DNA is also considered in terms of molecular mechanics
      methods and flexible docking techniques. MATERIALS AND METHODS: The cytotoxicity
      of compounds 10a, 11-oxo-N-[2-(pyrrolidino)ethylo]-11H-benzothiopyrano
      [3',2':2,3]pyrido[1,2-a]imidazo-2-carboxamide, 11-oxo-N-[2-(piperidino)ethylo]
      11H-benzothiopyrano [3',2':2,3]pyrido[1,2-a]imidazo-2-carboxamide and N-[2
      (morpholino)ethylo]-11-oxo-11H-benzothiopyrano [3',2':2,3]pyrido[1,2-a]imidazo-2
      carboxamide (10c-10e) was assessed in human tumor cell lines and xenografts using
      the sulforhodamine B assay, MTT assay and the clonogenic assay. The human ovarian
      xenograft, PXN/109TC, two human breast carcinomas, MT-1 and MCF-7, and the murine
      colon adenocarcinoma, MAC15A were used for the in vivo testing of compound 10a.
      In addition, the interaction between compound 10a and DNA is also considered in
      terms of molecular mechanics methods and flexible docking techniques. RESULTS:
      Two compounds, 10a and 10c, showed cytotoxic activity below 10 mM in the NCI in
      vitro screen of 60 human tumor cell lines. The IC50 value of compound 10a was 6.8
      mM and that of 10c, 8.3 mM. In addition, both compounds possessed differential
      activity against leukemia, colon and mammary cancer. The activity pattern was
      confirmed in two further screens using monolayer and clonogenic, assays. In vivo
      antitumor studies showed that 10a was active against the human mammary carcinoma
      MT-1 and murine colon cancer MAC15A. Marginal activity was observed in human
      ovarian cancer model PXN/109T/C and the compound was inactive in human mammary
      cancer MCF-7. CONCLUSION: The results warrant further in vivo testing of 10a in
      additional human solid tumor models. The molecular modeling showed that the
      planarity of the chromophore and the side-chain conformation could assist the
      insertion of compound 10a between the base pairs of the double helix. On the
      other hand, docking to the nucleotide sequence GGAATTGCCTCA suggested that the
      molecule could also act as a minor groove binder.

PMID- 15161045
TI  - Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and
      both are overexpressed in epithelial ovarian cancer.
AB  - Abnormal signal transduction arising from integrins and protein tyrosine kinases
      has been implicated in the initiation and progression of a variety of human
      cancers. Integrin-mediated signal transduction pathways require regulated
      cytoplasmic protein-protein interactions. However, little is known about integrin
      associated proteins and ovarian cancer. In our study we investigated the
      association of pp125FAK, a cytoplasmic tyrosine kinase, involved in anchorage
      independent growth of tumor cells, and the Four and a Half LIM domain (FHL)
      protein FHL2, which was recently shown to interact with integrins. Our data
      demonstrated that pp125FAK and FHL2 form a protein complex in human ovarian
      carcinoma. Furthermore, we showed that pp125FAK is overexpressed in epithelial
      ovarian cancer, but virtually absent in normal ovary. Our immunohistochemistry
      data showed that FHL2 protein expression is also augmented in epithelial ovarian
      cancer. Taken together, our results demonstrated for the first time FHL2
      expression in human ovarian cancer cells, suggesting an important functional role
      of pp125FAK and FHL2 complex in gynecologic malignancies.

PMID- 15161046
TI  - Electrofusion generates diverse DC-tumour cell hybrids for cancer immunotherapy.
AB  - BACKGROUND: Hybrid cells generated from dendritic cells (DC) and tumour cells
      provide tumour-associated antigens (TAA) in a polyvalent mode. The present study
      was designed to investigate the hybrid cell generation by dendritic cells and
      different tumour cell lines to establish an electrofusion protocol with an
      optimal fusion setting. MATERIALS AND METHODS: Hybrid cells from mature DC and
      tumour cells were generated by electrofusion. Fusion efficiency was determined by
      flow cytometry, as well as by light and fluorescence microscopy analyses.
      RESULTS: The gradual electrofusion process constituted different human dendritic
      cell tumour cell hybrids of high diversity depending on electrical and non
      electrical parameters. Factors influencing fusion frequency were determined by
      specific cell staining with mAbs, FACS analysis and trypan blue dye exclusion.
      CONCLUSION: Increased fusion efficiency was associated with reduced viability.
      The protocol presented in this work might be helpful for future fusion studies as
      a prerequisite for comparable in vitro and human vaccination trials.

PMID- 15161047
TI  - Three-dimensional culture and multidrug resistance: effects on immune reactivity
      of MCF-7 cells by monocytes.
AB  - BACKGROUND: Multicellular spheroids are known to be the most adapted model to
      keep the in vitro resistance properties of cells. This in vivo-like tissue
      culture representation was applied to investigate the immune reactivity of MCF-7
      cells by monocytes. MATERIALS AND METHODS: Human blood monocytes, obtained by
      elutriation, were co-cultured with multicellular tumor spheroids of drug
      sensitive (MCF-7S) and doxorubicin-resistant (MCF-7DXR) MCF-7 breast cancer
      cells. RESULTS: Tumor cells, according to their phenotype, induced differential
      recruitment and behavior of the immune cells towards the two types of spheroids.
      The secretion of various cytokines and the expression of several adhesion
      molecules were analysed. The MCF-7DXR/monocytes co-culture supernatant showed
      higher levels of IL-6 and IL-8 than the MCF-7S/monocytes co-culture supernatant.
      Cells from the MCF-7DXR spheroids expressed some adhesion molecules, CD-44 and CD
      54, leading to a strong cellular cohesion in comparison with the sensitive
      spheroids. CONCLUSION: The two spheroid phenotypes represented an excellent model
      system for determining the precise tumor microenvironment in which cells move,
      the crucial molecular requirements and the mechanisms by which immunotherapeutic
      strategies could be developed to eradicate chemo-resistant tumors.

PMID- 15161048
TI  - Structure-activity relationships of synthetic analogs of (-)-epigallocatechin-3
      gallate as proteasome inhibitors.
AB  - BACKGROUND: Cancer-related molecular targets of green tea polyphenols, such as (
      )-epigallocatechin-3-gallate [(-)-EGCG], remain unknown. We previously showed
      that (-)-EGCG is a potent and specific inhibitor of the proteasomal chymotrypsin
      like activity in vitro and in vivo. MATERIALS AND METHODS: EGCG amides and five
      simple analogs were prepared by enantioselective synthesis. Proteasome inhibition
      in vitro was measured by fluorogenic substrate assay and in vivo by accumulation
      of proteasome target proteins (p27, IkappaB-alpha and Bax). Inhibition of tumor
      cell proliferation was determined by G1 arrest, DNA fragmentation and colony
      formation inhibition. RESULTS: EGCG analogs with modifications in the A-ring, C
      ring or ester bond inhibit the chymotrypsin-like activity of purified 20S
      proteasome with altered potencies. However, these compounds were able to potently
      inhibit the proteasome activity in vivo and also suppress colony formation of
      prostate cancer LNCaP cells. Some compounds caused G1 arrest and DNA
      fragmentation in leukemia Jurkat T cells. However, these EGCG analogs caused no
      or little proteasome inhibition in normal or nontransformed cells. CONCLUSION:
      The A-ring and gallate ester/amide bond are essential for the proteasome
      inhibitory function of (-)-EGCG.

PMID- 15161049
TI  - Expression and localization of homeodomain proteins DLX4, HB9 and HB24 in
      malignant and benign human colorectal tissues.
AB  - BACKGROUND: The purpose of this study was to identify homeobox genes expressed in
      the human colon and to determine whether their expression levels were altered
      between matched non-malignant and malignant colon tissues. MATERIALS AND METHODS:
      Homeobox genes expressed in colon tissue were identified by reverse transcription
      polymerase chain reaction (RT-PCR). Antibodies were raised to the homeodomain
      proteins DLX4, HB9 and HB24 and immunohistochemistry was performed on 3
      moderately-differentiated tumors and their corresponding non-malignant colon
      tissue samples. RESULTS: The RT-PCR screen identified expression of DLX4, HB9,
      HB24 and MSX2 in the normal colon. Immunoaffinity purified polyclonal antisera
      raised against DLX4, HB9 and HB24 detect specific immunoreactivity in glandular
      epithelial cells, stromal cells of the lamina propria but not in the submucosa.
      Nuclear epithelial immunoreactivity of all three antibodies decreased in
      moderately-differentiated tumors compared to the corresponding matched non
      malignant mucosa. These data suggest that differential expression of HB9, HB24
      and DLX4 may be associated with colorectal carcinogenesis.

PMID- 15161050
TI  - Simultaneous measurement of nucleolin and estrogen receptor in breast cancer
      cells by laser scanning cytometry.
AB  - BACKGROUND: The purpose of the study was to test the feasibility of laser
      scanning cytometry (LSC) to simultaneously measure estrogen receptor (ER) and
      nucleolin (NU) expression in the nuclei of the same individual breast cancer
      cells. MATERIALS AND METHODS: Cancer cells from 64 breast tumors were labeled
      with anti-NU and biotinylated anti-ER antibodies, then with secondary FITC
      conjugated antibody and streptavidin-APC conjugate, respectively, and measured by
      LSC. The expression of NU in the nucleus and NU aggregates (NUA), number of NUA,
      nuclear and NUA areas and ER expression were assessed for aspiration each cell.
      RESULTS: ER-bound APC fluorescence correlated with nuclear NU (r=0.65; p<0.001)
      and NUA-bound FITC fluorescence (r=0.59; p<0.001). Good correlation was found
      between percentages of ER-positive cells in LSC and by image analysis in paraffin
      embedded sections (r=0.59, p<0.001). CONCLUSION: ER and NU expression can be
      measured simultaneously in the same nuclei of breast cancer cells.

PMID- 15161051
TI  - Activation of metalloproteinases-2 and -9 by interleukin-1alpha in S100A4
      positive liposarcoma cell line: correlation with cell invasiveness.
AB  - BACKGROUND: The S100A4 gene may affect the invasive properties of tumor cells
      through modulation of metalloproteinases (MMPs) and their inhibitors (TIMPs).
      MATERIALS AND METHODS: In the human liposarcoma cell line, SW872, we analyzed the
      expression of S100A4 protein by immunohistochemistry and flow cytometry. The
      production of MMP2, MMP9, TIMP1 and TIMP2 was assessed by gelatin zymography and
      enzyme-linked immunoabsorbent assay before and after interleukin-1alpha (IL
      1alpha) and interleukin-6 (IL-6) stimulation; cell invasiveness was measured by
      Matrigel invasion assay. RESULTS: S100A4-positive SW872 cells responded to IL
      1alpha with induction of immunoreactive MMP2 and TIMP1 and with activation of
      both MMPs, the latter significantly associated with an increase of cell
      invasiveness. Treatment with IL-6 induced less significant variations resulting
      in a more stable invasive behavior. CONCLUSION: These data show that S100A4
      positive SW872 respond to interleukins by influencing the behavior of factors
      involved in extracellular matrix degradation and emphasize the predominant role
      of MMP activity status on the positive regulation of cell migration mechanisms.

PMID- 15161053
TI  - Altered expression and new mutations in DNA mismatch repair genes MLH1 and MSH2
      in melanoma brain metastases.
AB  - Brain metastases, including those of malignant melanoma (known for its high
      genomic instability), are the most common intracranial tumors. The main objective
      of this study was to investigate expression and mutation in the DNA mismatch
      repair system in melanoma brain metastases. Expression of MLH1, MSH2, PMS1 and
      PMS2 was investigated immunohistochemically in 31 melanoma metastatic tumors.
      Mutational analysis of MLH1 and MSH2 was performed in 17 melanoma brain
      metastases. Loss of MLH1 and MSH2 expression was found in 10/31 and 12/31 tumors.
      PMS1 (27/31) and PMS2 (28/31) expression was preserved in the majority of
      lesions. Potential missense mutation was found in MSH2 (exon 13) in 2/17
      melanomas. Mutation in the intron sequence between exon 14 and 15 of MLH1 (exon
      15) was observed in 4/17 cases. Our results indicate that the two major DNA
      mismatch repair genes, MLH1 and MSH2, are more frequently affected by alterations
      in the DNA mismatch repair system than the helper genes PMS1 and PMS2. The
      presence of mutations of MSH2 and MLH1 in melanoma brain metastases, which has
      not been found in primary melanomas, indicates the high genomic instability of
      melanoma brain metastases.

PMID- 15161052
TI  - Comparison of surface HLA class I levels in squamous cell carcinoma cell lines of
      the head and neck.
AB  - BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN) are the most
      frequent malignancies in this region. Down-regulation of human leukocyte antigen
      (HLA) class I was found to be implicated in the immune escape of these tumors.
      MATERIALS AND METHODS: Cell surface expression levels of several HLA class I
      antigens were evaluated in 21 SCCHN cell lines utilizing FACS analysis. RESULTS:
      Expression levels of HLA-antigens varied significantly between the investigated
      cell lines. On average higher HLA-B27 expression levels were observed in cell
      lines from younger and female patients. CONCLUSION: Our data confirms down
      regulation of HLA class I to be an important event in SCCHN. However, since
      several SCCHN cell lines also exhibited high HLA levels, other mechanisms than
      HLA down-regulation also need to be considered as a cause for disease
      progression. Further studies will be required to elucidate the potential role of
      HLA-B27 in SCCHN.

PMID- 15161054
TI  - Curcumin and resveratrol induce apoptosis and nuclear translocation and
      activation of p53 in human neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) is an aggressive childhood cancer of the
      peripheral nervous system arising from neural crest sympathoadrenal progenitor
      cells. Despite current rigorous treatment protocols, prognosis for high stage NB
      patients is poor and so there remains a need for more effective, less cytotoxic
      treatments. Curcumin and resveratrol possess anti-tumor properties in adult
      cancer models and negligible toxicity in normal cells, but little is known about
      the effect of these agents on pediatric cancers. MATERIALS AND METHODS: Stage 4
      MYCN-amplified NB cell lines, with wild-type or mutant p53, were treated with
      curcumin and resveratrol and analyzed for effects on proliferation, cell cycle,
      induction of apoptosis and p53 function. RESULTS: Treatment induced a dose- and
      time-dependent decrease in cell viability, cell cycle arrest and induction of
      apoptosis. Treatment transiently up-regulated p53 expression and induced nuclear
      translocation of p53, followed by induction of p21(WAF-1/CIP-1) and Bax
      expression. CONCLUSION: Observations suggest that the cytotoxicity, cell cycle
      arrest and apoptosis induced by curcumin and resveratrol in NB cells may be
      mediated via functionally activated p53 and merit further study.

PMID- 15161055
TI  - The 3,4-dihydroxyl groups are important for trans-resveratrol analogs to exhibit
      enhanced antioxidant and apoptotic activities.
AB  - We compared the abilities of trans-resveratrol and seven analogs to inhibit an
      azo compound-induced peroxidation of linoleic acid in vitro and to induce
      apoptosis in cultured human leukemia cells. The results showed that both the
      antioxidant and apoptotic activities of the analogs containing 3,4-dihydroxyl
      groups were significantly higher than those of the trans-resveratrol and the
      other analogs. Hence, the 3,4-dihydroxyl groups were important for trans
      resveratrol analogs to exhibit concurrent high antioxidant and apoptotic
      activities.

PMID- 15161056
TI  - Capsaicin-mediated denervation of sensory neurons promotes mammary tumor
      metastasis to lung and heart.
AB  - Capsaicin specifically activates or destroys small diameter nociceptive sensory
      neurons that contain the capsaicin receptor, also called vanilloid receptor 1.
      Neurons sensitive to capsaicin mediate inflammatory pain and are important
      targets for management of chronic pain. These neurons also regulate local tissue
      homeostasis, inflammation, healing and development, especially under conditions
      of psychological stress. Stress contributes to increased cancer recurrence and
      metastasis through as yet undefined mechanisms. Likewise, activity of capsaicin
      sensitive neurons is altered by pathological conditions that may lead to
      metastatic growth (e.g. stress). Therefore, we examined effects of a treatment
      that induces sensory nerve denervation on breast cancer metastases. Systemic
      denervation of sensory neurons caused by treatment with 125 mg/kg capsaicin
      resulted in significantly more lung and cardiac metastases in adult mice injected
      orthotopically with syngeneic 4T1 mammary carcinoma cells than was observed in
      vehicle-treated controls. Heart metastases, normally very rare, occurred as
      pericardial nodules, intra-myocardial nodules, or combined pericardial-myocardial
      lesions. Since the rate of primary tumor growth was unaffected, effects on
      metastases appear to be host tissue-specific. Although preliminary, these
      observations provide one possible explanation for resistance of cardiac tissue to
      tumor involvement and highlight contributions of host tissue, including sensory
      neurons, in the efficiency of cancer metastasis.

PMID- 15161057
TI  - Altered mRNA expression of the Rb and p16 tumor suppressor genes and of CDK4 in
      transitional cell carcinomas of the urinary bladder associated with tumor
      progression.
AB  - Based on the concept that tumor suppressor genes are involved in the pathogenesis
      of urinary bladder carcinogenesis, we analysed the mRNA expression of the
      retinoblastoma (Rb) and p16 (CDKN2, INK4A, MTS1) genes as well as of the proto
      oncogene cyclin D-dependent kinase 4 (CDK4) in 71 transitional cell carcinomas
      (TCC) of the urinary bladder in relation to the tumor grades and stages, and with
      reference to certain lifestyle and occupational risk factors. Using real-time
      quantitative reverse transcription-polymerase chain reaction, high-stage muscle
      invasive TCC expressed the Rb, p16 and CDK4 mRNA at lower levels than low-stage
      superficial cancers, indicating down-regulation to be linked with tumor
      progression. The drop of the expression in the group of grade 2 TCC when invading
      the muscle layer compared to grade 2 carcinomas with a superficial pattern of
      growth is considered to represent a key event in promoting urothelial
      carcinogenesis in this subset of carcinomas. The protein expression of the Rb
      gene evaluated by immunohistochemistry proved to be closely related to the tumor
      grades and stages as well as to the mRNA expression, high-grade and high-stage
      TCC disclosing a lower rate of positive immunoreactivity than low-grade and low
      stage carcinomas. The p16 protein product was expressed at a lower level in grade
      3 than in grade 1 TCC, but there was no correlation with the tumor stages or the
      mRNA expression. TCC with loss of heterozygosity (LOH) at the INK4A region showed
      a decreased expression of p16 mRNA compared to those without an allelic loss.
      Tobacco smoke was not identified to substantially modulate the Rb/p16/CDK4
      pathways, except for a ten-fold elevated mRNA expression of the p16 gene in TCC
      of light compared to heavy smokers. Heavy coffee consumption was associated with
      a reduced expression of CDK4 mRNA. Among occupational exposures, TCC of patients
      in contact with stone dust, paints and lacquer, plastics, wood and wood
      preservers and chemical solvents and adhesives displayed altered partly elevated,
      partly reduced levels of Rb, p16 and CDK4 mRNA compared to non-exposed subjects.
      Although the underlying molecular-genetic pathways are not yet fully understood,
      the current results suggest functional reduction of the tumor suppressor genes Rb
      and p16 to be associated with progression of bladder cancer to a more malignant
      and aggressive behaviour.

PMID- 15161058
TI  - Human beta-defensin-2 in oral cancer with opportunistic Candida infection.
AB  - Candida albicans (CA) is a frequent opportunistic pathogen in cancer patients.
      Usually, human surfaces are protected, apart from physical barriers, by the
      production of human beta-defensins (hBD). hBD-2 shows a potent antimicrobial
      activity against CA. We therefore investigated whether CA induces hBD-2
      expression in primary oral cells and if immunosuppressive betamethasone alters
      hBD-2 expression. Additionally, we studied, whether a lack of hBD-2 expression
      could explain opportunistic infection of tonsillar cancer. Primary oral
      epithelial cells and fibroblasts were stimulated with Candida albicans in a time-
      and dose-dependent manner with or without betamethasone preincubation. Total RNA
      from oral cells and specimens was isolated and hBD-2 expression was analyzed by
      semiquantitative RT-PCR. Our data demonstrate that opportunistic CA induced hBD-2
      expression in a time- and dose-dependent manner, suggesting hBD-2 to be a fast
      antifungal, epithelia-derived immune response. Treatment with glucocorticoid
      could lead to diminished innate immunity based on suppression of inducible AP.
      Malignant transformation induces alteration of hBD-2 expression and leads to a
      reduced hBD-2 expression and subsequentially to Candida colonization on oral
      SCCs.

PMID- 15161059
TI  - The inflammatory response to cardiopulmonary bypass: a therapeutic overview.
AB  - The demographic of cardiac surgery patients continues to evolve to include older,
      sicker candidates, all the while maintaining an expectation of excellent
      outcomes. These latter results can only be achieved by the parallel advancement
      and re-examination of the technology of cardiopulmonary bypass (CPB); the key
      tool used daily by surgical teams worldwide. In this review, we will provide an
      overview of integrated therapeutic strategies that can be utilized to minimize
      the complex and myriad changes related to inflammation after CPB with the
      understanding that this may abrogate the detrimental end-organ and systemic
      effects of blood activation. Therapeutic strategies specifically related to the
      technology can be classified into those targeting biomaterial dependent or
      independent processes. The former can be addressed by the utilization of
      currently available biocompatible surfaces such as with heparin-coated circuits,
      phosphorylcholine-coated circuits ('biomembrane mimicry') and circuits composed
      of copolymers containing surface-modifying additives. The most important
      strategies related to biomaterial independent activation include the modification
      of techniques related to cardiotomy blood management and blood filtration.
      Finally, all of these strategies must be integrated and tailored with
      complementary pharmacologic agents such as aprotinin and steroids to optimize
      anti-inflammatory synergism. Only if we are armed with a comprehensive knowledge
      of the molecular and cellular basis for these strategies will we be able to
      continue to evolve our treatment in parallel with our patients to achieve these
      goals.

PMID- 15161060
TI  - Leukocyte filtration and aprotinin: synergistic anti-inflammatory protection.
AB  - Cardiopulmonary bypass activates an array of cellular and humoral inflammatory
      mechanisms that culminate in diverse or organ-specific injury. A manifestation of
      inflammatory injury to the heart, atrial fibrillation ranks among the most
      frequent and potentially life-threatening postsurgical complications. Pulmonary
      manifestations of the inflammatory response are also of major concern.
      Neutrophils activated by passage through the extracorporeal circuit inflict local
      injury and provoke the inflammatory cascade by producing oxyradicals and
      proinflammatory factors. This study tested if a combination of leukocyte
      depletion and aprotinin suppression of neutrophils could minimize postbypass
      atrial fibrillation and pulmonary dysfunction. In part one, two randomized groups
      of 90 patients undergoing primary coronary artery bypass grafting received full
      Hammersmith aprotinin alone (control group) or combined with leukofiltration
      (study group) and were prospectively examined. The dual treatment decreased the
      incidence of postoperative atrial fibrillation (7 of 90, 7.8%) by 67% versus
      aprotinin alone (21 of 90, 23.3%). Respiratory gas exchange in these patients was
      assessed from pulmonary shunt fraction. In the first two hours postbypass,
      pulmonary shunt fraction in the dual treatment group increased 40% less than in
      the group receiving aprotinin alone (p = 0.002), and subsided more quickly and
      completely over the next six hours. In part two, the cardiopulmonary bypass group
      receiving aprotinin + leukofiltration was retrospectively compared with 45
      patients undergoing off-pump coronary revascularization. A strong, albeit not
      statistically significant trend (p = 0.08) toward a lower incidence of atrial
      fibrillation was found in the dual treatment group versus the off-pump group (8
      of 45, 17.8%). These findings suggest that combining mechanical and pharmacologic
      suppression of the systemic inflammatory response could mitigate its deleterious
      arrhythmic and pulmonary complications.

PMID- 15161061
TI  - Contaminating fat in pericardial suction blood: a clinical, technical and
      scientific challenge.
AB  - Stroke and diffuse brain damage after cardiac surgery are too common. It is
      important to find means to reduce the incidence in view of future competition to
      surgery from less invasive procedures. Stroke is fairly well defined in clinical
      terms and with several identified mechanisms. Diffuse brain damage is less well
      defined and more complex in nature. One suggested mechanism is from cerebral fat
      microembolization of retrieved pericardial suction blood (PSB). The present study
      aimed to describe a simple method to measure fat content of PSB, how experimental
      artefacts interfere with the results, and how the unstable character of a fat
      blood suspension can be used to design a simple fat-separation system. The
      quantity of small amounts of fat can be amplified by centrifugation to the
      tapered tip of a standard glass pipette. The coefficient of variation after
      repeated experiments was 9.5%. PSB after coronary bypass surgery contained 0.22
      +/- 0.04% fat of which 15 +/- 3% was bound to the surface of the plastic
      collecting bag. Experimentation requires standardized routines. Static
      incubation, blood-fat mixing routines, and transfer steps of blood samples
      between syringes induce substantial artefacts from spontaneous density separation
      and surface-adhesion of fat. Soya oil is a common reference substance replacing
      human fat in technical laboratory science, but is associated with artefacts of
      its own. These artefacts cause problems during experimentation but the oil is a
      good resource in the design of a simple fat-separation system.

PMID- 15161062
TI  - Clinical significance of coated extracorporeal circuits: a review of novel
      technologies.
AB  - Coating of extracorporeal circuits may be a solution to prevent adverse effects
      induced by the contact of blood elements and proteins with foreign surfaces. This
      paper reviews the recent novel coating technologies and compares their documented
      in vitro and ex vivo advantages under the clinical setting. Data presented have
      also been supported by postclinical biomaterial research to verify
      biocompatibility and hemocompatibility.

PMID- 15161063
TI  - The role of the Molecular Adsorbents Recirculating System (MARS) in the
      management of liver failure.
AB  - Albumin-bound toxins accumulate in liver failure, and are believed to contribute
      to the development of the associated end-organ dysfunctions (kidney, circulation,
      brain). The scavenging functions of albumin are utilized in albumin dialysis for
      toxin removal. The Molecular Adsorbents Recirculating System (MARS) is an
      extracorporeal liver support device based on dialysis across an albumin
      impregnated membrane, using 20% albumin as dialysate. Charcoal and anion exchange
      resin columns in the circuit help cleanse and regenerate the dialysate. Clinical
      studies over the last decade have demonstrated proven reduction in
      hyperbilirubinaemia, along with an improvement in hepatic encephalopathy,
      systemic haemodynamics and renal function in liver failure patients, as well as
      apparent improvement in survival. However, the specific mechanisms underlying
      these observed clinical changes are as yet unclear. The results of larger
      controlled clinical trials, as well as studies investigating the
      pathophysiological basis of its effect, are awaited.

PMID- 15161064
TI  - Bubbles and bypass: an update.
AB  - Bubbles in the bloodstream are not a normal condition--yet they remain a fact of
      cardiopulmonary bypass (CPB), having been extensively studied and documented
      since its inception some 50 years ago. While detectable levels of gaseous
      microemboli (GME) have decreased significantly in recent years and gross air
      embolism has been nearly eliminated due to increased awareness of etiologies and
      technological advances, methods of use of current perfusion systems continue to
      elicit concerns over how best to totally eliminate GME during open-heart
      procedures. A few studies have correlated adverse neurocognitive manifestations
      associated with excessive quantities of GME. Newer techniques currently in vogue,
      such as vacuum-assisted venous drainage, low-prime perfusion circuits, and carbon
      dioxide flooding of the operative field, have, in some instances, exacerbated the
      problem of gas embolism or engendered secondary complications in the safe conduct
      of CPB. Doppler monitoring (circuit or transcranial) primarily remains a research
      tool to detect GME emanating from the circuit or passing into the patients'
      cerebral vasculature. Newer developments not yet widely available, such as
      multiple-frequency harmonics, may finally provide a tool to distinguish
      particulate microemboli from GME and further delineate the clinical significance
      of GME.

PMID- 15161065
TI  - Does modified ultrafiltration reduce the systemic inflammatory response to
      cardiac surgery with cardiopulmonary bypass?
AB  - Cardiopulmonary bypass (CPB) is associated with an accumulation of total body
      water and a systemic inflammatory response syndrome (SIRS), which, in turn, is
      associated with organ dysfunction and postoperative morbidity. It has been
      suggested that modified ultrafiltration (MUF) may be capable of reducing SIRS and
      improving clinical outcome by filtering out the inflammatory mediators generated
      during CPB. This paper reviews the data regarding the use of MUF in paediatric
      and adult settings. Specifically, three issues will be considered: 1) Does MUF
      improve clinical outcome? 2) Does MUF reduce the systemic inflammatory response
      to cardiac surgery with CPB? 3) Is MUF more effective than conventional
      ultrafiltration in improving clinical outcome?

PMID- 15161066
TI  - Methodological approach in adopting off-pump coronary artery bypass surgery in a
      British cardiothoracic unit: Harefield experience.
AB  - The theoretical and practical disadvantages of coronary artery bypass graft
      surgery using cardiopulmonary bypass with cardioplegic arrest are well reported
      in the literature. Encouraged by our work and others, we adopted a systematic
      approach to the application of off-pump coronary artery bypass surgery. We aimed
      to validate the non-selective use of the off-pump technique in all patients and
      assess the outcome in specific patient groups including: patients with ischaemic
      left ventricular dysfunction, female and high-risk patients. We investigated
      specific technical details related to off-pump surgery including: the potential
      effect of the distortion of the mitral valve on haemodynamic stability
      intraoperatively and the feasibility of sequential coronary artery bypass
      grafting using the off-pump technique. We also compared the outcome to the
      national United Kingdom performance in a risk-stratified manner. An extensive
      retrospective data review for comparative analysis of outcome was carried out at
      both local and multi-centre levels. This showed that off-pump surgery was
      feasible for all patients, and provided a better outcome in patients with
      ischaemic left ventricular dysfunction, female and high-risk patients. The
      distortion of the mitral valve contributed to the haemodynamic instability. In
      conclusion, off-pump surgery is safe and provides better outcome in specific
      patient groups.

PMID- 15161067
TI  - Intranasal immunization with genetically detoxified diphtheria toxin induces T
      cell responses in humans: enhancement of Th2 responses and toxin-neutralizing
      antibodies by formulation with chitosan.
AB  - We previously reported that intranasal immunization with a non-toxic mutant cross
      reacting material (CRM)197 of diphtheria toxin, formulated with chitosan,
      generated protective neutralizing antibodies in mice and guinea pigs.
      Furthermore, we demonstrated that intranasal delivery of a powder formulation of
      the CRM197-based vaccine was well tolerated and significantly boosted antibody
      responses in adult volunteers. Here we report that intranasal booster
      immunization with CRM197 alone or with chitosan induced systemic T cell
      responses. We addressed for the first time the induction of T cell subtypes
      following intranasal vaccination in humans. Intranasal vaccination with CRM197,
      like parenteral immunization with a conventional diphtheria toxoid vaccine,
      enhanced antigen-specific IFN-gamma production. However, formulation of the nasal
      diphtheria vaccine with chitosan significantly augmented Th2-type responses,
      which correlated with protective levels of toxin-neutralizing antibodies in
      intranasally boosted individuals. The results suggest that vaccines capable of
      inducing strong Th2-type responses, such as CRM197 formulated with chitosan, have
      potential for the development of a protective mucosal vaccine against diphtheria
      in humans. Furthermore, our findings demonstrate that mucosal subunit vaccines
      with appropriate delivery systems have considerable potential for booster
      immunization of adults.

PMID- 15161068
TI  - Evaluation of BBG2Na in infant macaques: specific immune responses after
      vaccination and RSV challenge.
AB  - We have addressed the safety of alum-adsorbed BBG2Na, a recombinant respiratory
      syncytial virus (RSV) subunit vaccine, in infant macaques. Animals received two
      vaccinations, and were challenged 4 months later with RSV. In two of four BBG2Na
      vaccinated animals, specific IL-13 producing T cells were detected. Upon
      challenge, low level pulmonary eosinophilia was observed in the same two animals.
      Although the levels of these responses were substantially lower than those
      observed in the FI-RSV controls, these data suggest that more extensive studies
      focusing on immunopathological safety of alum-adsorbed BBG2Na in non-human
      primates would be required before proceeding to clinical trials in seronegative
      infants.

PMID- 15161069
TI  - Vaccination of infant macaques with a recombinant modified vaccinia virus Ankara
      expressing the respiratory syncytial virus F and G genes does not predispose for
      immunopathology.
AB  - We have evaluated the safety and immunogenicity of a recombinant modified
      vaccinia virus Ankara (MVA) vector expressing the respiratory syncytial virus
      (RSV) fusion (F) and attachment (G) proteins in infant macaques. Animals were
      vaccinated twice and 4 months later challenged with RSV. Although vaccination did
      not predispose for immunopathology upon challenge, we were also unable to
      demonstrate protection. Since vaccination had resulted in priming for secondary
      immune responses upon challenge, we suggest that vaccination efficacy will have
      to be improved by using MVA in a prime-boost strategy.

PMID- 15161070
TI  - Precise answers to the wrong question: prospective clinical trials and the meta
      analyses of pneumococcal vaccine in elderly and high-risk adults.
AB  - Ten prospective clinical trials conducted in elderly and high-risk adults have
      failed to show that pneumococcal vaccine prevents pneumococcal bacteraemia and
      all pneumonia. Several of these trials focused on unrepresentative populations
      and most had serious methodological problems. Few adequately considered sample
      size requirements in pre-trial planning. Retrospective sample size calculations
      based on the findings of the individual trials showed that none was large enough
      to rule out false negative results. Five published meta-analyses have attempted
      to determine the efficacy of pneumococcal vaccine by pooling the results of the
      individual clinical trials. The resulting study populations often were not
      representative of the populations of elderly and high-risk adults for whom
      vaccination is recommended. The meta-analysts often omitted clinical trials that
      should have been evaluated, included other trials that should have been omitted
      and miscounted the numbers of subjects and outcome events in the individual
      trials. Retrospective sample size calculations showed that none of the meta
      analyses included an adequate number of person years of observation to rule out
      false negative results. The prospective clinical trials and meta-analyses of
      pneumococcal vaccine in elderly and high-risk adults have been inconclusive, but
      they should not be regarded as negative studies. The clinical effectiveness of
      vaccination in preventing pneumococcal bacteraemia in elderly and high-risk
      adults has been demonstrated in observational studies, and vaccination is cost
      effective. This evidence is sufficient to justify wider use of pneumococcal
      vaccine.

PMID- 15161071
TI  - Protection against plague afforded by immunisation with DNA vaccines optimised
      for expression of the Yersinia pestis V antigen.
AB  - DNA vaccine vectors were produced which were optimised for expression of the
      Yersinia pestis V antigen in the BALB/c mouse model. Six different eukaryotic
      promoters were compared, resulting in the selection of the CMV promoter with an
      additional translational enhancer downstream. Surprisingly, alteration of the
      codon usage of the lcrV gene encoding V antigen for expression in murine cells
      was not found to improve the antibody responses generated against V antigen. The
      DNA vaccine was subsequently evaluated in its delivery via intramuscular
      injection compared to gene-gun administration. Gene-gun delivery was found to
      induce significantly higher V antigen-specific antibody responses and also
      afforded the highest level of protection against Y. pestis challenge. In
      addition, the protection achieved could be increased by using a 'prime and boost'
      strategy, administering the DNA vaccine followed by recombinant V antigen. These
      results show promise for a DNA vaccine against plague.

PMID- 15161072
TI  - Safety and immunogenicity of a booster dose of inactivated poliovirus vaccine
      produced in vero-cells.
AB  - Statens Serum Institut has developed a new vero-cell culturing technique for the
      manufacturing of inactivated poliovirus vaccine (IPV). This technique implies
      that the cultivation of cells and poliovirus is performed in a medium free of
      materials of animal origin and free of antibiotics. In a double-blind randomised
      clinical trial, IPV(vero) manufactured by this new technique was compared to
      conventionally produced IPV(mkc). One hundred and twenty-nine (129) healthy adult
      volunteers were given booster vaccinations of IPV(vero) (65) or IPV(mkc) (64).
      Both vaccines were well tolerated and resulted in excellent booster responses. No
      statistically significant differences were seen between the study groups.

PMID- 15161073
TI  - ISCOM based vaccines for cancer immunotherapy.
AB  - Immunostimulating complex (ISCOM) vaccines are particulate antigen delivery
      vehicles composed of saponin, cholesterol, phospholipid and immunogen. Here we
      illustrate that ISCOM-based vaccines represent an attractive modality for the
      development of anti-cancer vaccines. Using murine models and a model cancer
      antigen, ISCOM vaccines were shown to induce potent CD8 T cell responses, to
      mediate protection in three different tumor models, to promote Th1-biased
      immunity, and to induce CD8 T cell responses in the absence of CD4+ T cell help.
      The former three activities were also found to be substantially improved when the
      vaccine antigen was associated with the ISCOM structure. Furthermore, the
      presence in vivo of pre-existing antibodies against the vaccine antigen did not
      inhibit CD8 T cell induction by the ISCOM vaccine. Although vaccination was
      effective against challenge with vaccine-antigen expressing tumors, no activity
      against neighboring vaccine-antigen negative tumor cells was observed, indicating
      that determinant spreading or bystander activity does not lead to significant
      anti-cancer activity.

PMID- 15161074
TI  - Prospective population-based incidence of Haemophilus influenzae type b
      meningitis in Thailand.
AB  - There are limited prospective data for Haemophilus influenzae type b (Hib)
      disease in Asia, where some countries are considering vaccine introduction. A
      prospective population-based study was conducted to measure the incidence of Hib
      meningitis in children in two northern provinces of Thailand. Children <5 years
      with symptoms consistent with bacterial meningitis were enrolled in the study if
      inclusion criteria were met. The study enrolled 598 children with clinical
      meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial
      meningitis was 26.6/100,000 children <5 years per year. There were four cases of
      laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per
      year). These findings suggest a relatively low incidence of Hib meningitis.
      However, additional data from studies of pneumonia are needed to define the Hib
      disease burden in Thailand.

PMID- 15161075
TI  - Comparison of different routes of vaccination for eliciting antibody responses in
      the human stomach.
AB  - Determination of optimal routes to induce mucosal immune responses locally in the
      stomach and duodenum are important steps in the development of vaccines against
      Helicobacter pylori infection. In this study, we immunized H. pylori-infected
      individuals either nasally or rectally with a model antigen, i.e. cholera toxin B
      subunit, and compared the immune responses after these routes with the responses
      after oral or intrajejunal vaccination. Specific antibody levels in serum as well
      as specific antibody levels and antibody-secreting cells in biopsies from antrum
      and duodenum were determined by ELISA and ELISPOT methods. In contrast to oral
      vaccination, nasal and rectal vaccination did not induce significant increases in
      specific antibody-secreting cells either in the antrum or duodenum. Furthermore,
      when analyzing the antibody levels in saponin extracted biopsies, intrajejunal
      vaccination was superior to both nasal and rectal vaccination in inducing antigen
      specific IgA levels in the stomach. We conclude that oral vaccination is the
      optimal route for induction of antigen-specific IgA antibody responses in the
      stomach and duodenum of humans, while nasal or rectal vaccination is less
      suitable for this purpose.

PMID- 15161076
TI  - Immunization of chimpanzees with an envelope protein-based vaccine enhances
      specific humoral and cellular immune responses that delay hepatitis C virus
      infection.
AB  - Two chimpanzees, one naive (Ch1601) and one recovered from hepatitis C virus
      (HCV) acute infection (Ch1587), were vaccinated with recombinant envelope
      glycoproteins (E1E2) and then challenged with 100 CID50 of HCV. Results of the
      challenge were compared to infection in a non-vaccinated control animal.
      Immunization generated high antibody titers to E1E2 including antibody
      specifically directed to the hypervariable region 1 (HVR1) in addition to strong
      and specific HVR1 T-cell proliferative responses. Upon challenge with HCV,
      viremia was delayed 3 weeks in both vaccinated animals compared to the non
      immunized (control) animal. Ch1601 HCV RNA titers were maintained below 5 x 10(4)
      copies/ml, and alanine aminotransferase levels were only minimally elevated. An
      increase in intrahepatic cytokine mRNA levels coincided with a fall in HCV RNA to
      non-quantifiable levels. Despite this apparent control of virus replication the
      animal became persistently infected. Ch1587 had a significantly shorter and
      milder viremia, compared to the re-infection of the non-vaccinated control
      animal. This data indicates that a strategy inducing a T-cell immune response
      combined with antibody responses to E1E2 would make a viable candidate for an HCV
      vaccine.

PMID- 15161077
TI  - The role of pharmacists in the delivery of influenza vaccinations.
AB  - OBJECTIVES: The purpose of this study is to determine whether influenza vaccine
      rates have increased in states where pharmacists can give vaccines. METHODS:
      Secondary analysis of the Behavioral Risk Factor Surveillance System (BRFSS) from
      the years 1995 and 1999. Information regarding legislation allowing pharmacists
      to administer vaccines was obtained from the American Pharmaceutical Association.
      RESULTS: Individuals aged 65 years and older who lived in states where
      pharmacists could provide vaccines had significantly higher (P < 0.01) influenza
      vaccine rates than individuals of this age who resided in states where
      pharmacists could not provide vaccines. CONCLUSIONS: Allowing pharmacists to
      provide vaccinations is associated with higher influenza vaccination rates for
      individuals aged 65 years and older.

PMID- 15161078
TI  - Trypanosome microtubule-associated protein p15 as a vaccine for the prevention of
      African sleeping sickness.
AB  - Trypanosomes cause African sleeping sickness, affecting millions of humans and
      animals. We tested trypanosome microtubule-associate protein (MAP p15) as a
      vaccine in mice, and show that p15 (native or recombinant) generated up to 100%
      protection from an otherwise lethal challenge of a heterologous strain of
      Trypanosoma brucei. We also tested the adenovirus as a vaccine delivery system
      and show that both adenoviral vector containing p15 gene or control adenovirus
      containing lacZ gene generated a protective response and exhibited strong CD8+ T
      cell proliferation. These results suggest that the p15 protein itself is an
      effective vaccine and that the adenovirus may be used to mount a non-specific
      cellular immune response.

PMID- 15161079
TI  - Th-1/Th-2 type cytokine profiles of pig T-cells cultured with antigen-treated
      monocyte-derived dendritic cells.
AB  - To examine the effects of cytokine environment at the time of antigenic exposure
      on T-cell cytokine profiles following T-cell-antigen presenting cell (APC)
      interaction, pig monocyte-derived dendritic cells (mDCs) were treated with hen
      egg white lysozyme (HEWL) or killed Mycobacterium tuberculosis (Mtb) alone or
      with a recombinant pig cytokine (TNF-alpha, interleukin (IL)-12, IL-10,
      interferon (IFN)-gamma or IL-6) and then incubated with autologous T-cell
      enriched lymphocytes. Messenger RNA was isolated from the T-cells and used to
      evaluate the effects of treatment on IL-12p35, IFN-gamma, IL-4, IL-10 and IL-13
      expression using RT-PCR. T-cells exposed to HEWL-treated mDCs expressed high IL
      13 and moderate IL-10 and IFN-gamma, suggesting T-helper 2 (Th-2) bias. Addition
      of any cytokine during HEWL treatment of mDCs reduced subsequent expression of IL
      10 and IL-13 by T-cells. Added IL-12 increased IFN-gamma mRNA. T-cells exposed to
      Mtb-treated mDCs expressed increased IFN-gamma and decreased IL-10 suggesting Th
      1 bias. Addition of cytokines to mDCs treated with Mtb altered T-cell cytokine
      mRNA expression such that TNF-alpha, IFN-gamma or IL-12 increased IFN-gamma; IL
      12 and IFN-gamma suppressed IL-10, while IL-10 and IL-12 enhanced IL-13.
      Messenger RNA for IL-4 and IL-12p35 was not detected in the T-cells. Results
      suggest Th-1/Th-2 type response bias in pigs T-cells as a function of antigen
      type and that cytokine environment at the time of antigen-mDC interaction alters
      cytokine profiles of T-cells responding to antigen-pulsed mDCs. Hence, cytokines
      may allow designed steering of porcine immune response.

PMID- 15161080
TI  - Immune responses to a GnRH-based anti-fertility immunogen, induced by different
      adjuvants and subsequent effect on vaccine efficacy.
AB  - A modified GnRH peptide (CHWSYGLRPG-NH2) was conjugated to tetanus toxoid and
      formulated with different adjuvants (non-ionic surfactant vesicles, aluminium
      hydroxide, Quil A, PLGA (poly(lactide-co-glycolide)/triacetin), and Quil A/PLGA).
      A comparison of the anti-fertility efficacy of the formulations was made by
      examining specific antibody levels, antibody subclasses, endocrine ablation and
      gonadal atrophy. The production of IgG2b antibody provided the best correlation
      for castration. PLGA was considered the most effective adjuvant as it produced a
      consistent anti-fertility response in all the treated animals.

PMID- 15161081
TI  - Expression and characterisation of recombinant oligomeric envelope glycoproteins
      derived from primary isolates of HIV-1.
AB  - The production, purification and characterisation of recombinant gp140 oligomeric
      envelope glycoproteins derived from six primary isolates of HIV-1 (covering
      clades A, B, C, D, F and O) are described. Using a Chinese hamster ovary cell
      expression system, expression levels of between 0.1 and 1 mg/l cell-conditioned
      culture media were obtained, and purified to >95% by affinity chromatography. A,
      B, D, F and O clade gp 140s were found to be multimeric, bind to a panel of
      defined env-specific monoclonal antibodies and interact with CD4 and CXCR4,
      demonstrating correct folding. Their immunogenicity was confirmed by the
      generation of high-titre anti-gp140 antibodies in rabbits. The C clade gp140 was
      incorrectly folded and poorly antigenic. Despite the presence of an unmodified
      gp120/41 cleavage site, only the B clade gp140 showed significant processing to
      gp120 and gp41. Each gp140 has a specific pattern of oligomerisation, and varies
      in its resistance to reducing agents and salt concentration. The binding of gp140
      to soluble and cell-surface CD4 and CXCR4 is related to the degree of
      oligomerisation. The C1 and C5 regions, CD4 binding domain and the epitope
      defined by the 2G12 monoclonal antibody were well exposed, but the C-terminal
      region of the extracellular domain of gp41 appears to be occluded by
      oligomerisation. These reagents have potential as immunogens for use in vaccine
      development.

PMID- 15161082
TI  - Scientific challenges for the quality control and production of group C
      meningococcal conjugate vaccines.
AB  - Recommendations (formerly known as requirements) for meningococcal polysaccharide
      vaccines were adopted by the World Health Organisation (WHO) Expert Committee on
      Biological Standardisation in 1976 and amended in 1978 and 1981. In clinical
      studies, these vaccines have been shown to have efficacy of at least 90% and have
      proved to be highly effective in vaccination programmes. Nevertheless, their
      inability to elicit protective responses in young infants or to induce good
      immunological memory has prevented their implementation in national infant
      immunisation schedules. Following the successful introduction of the Haemophilus
      influenzae type b conjugate (Hib) vaccines, considerable progress has been made
      in the development of similar conjugate vaccines based on meningococcal group C
      capsular polysaccharide. Controlled clinical trials have demonstrated that they
      induce protective levels of antibodies to group C polysaccharide in all age
      groups and, as T-cell dependent antigens, induce immunological memory and
      affinity maturation of anti-capsular antibodies. Such vaccines have been shown to
      offer protective immunity following the introduction of group C conjugates in the
      UK. The World Health Organisation has produced recommendations for the production
      and control of these new vaccines.

PMID- 15161083
TI  - Specific erythrocyte binding capacity and biological activity of Plasmodium
      falciparum-derived rhoptry-associated protein 1 peptides.
AB  - Rhoptry-associated protein 1 (RAP1) is a merozoite antigen within Plasmodium
      falciparum rhoptries as yet having no specific function described for it.
      Synthetic peptides spanning the RAP1 sequence were tested in erythrocyte binding
      assays to identify possible RAP1 functional regions. Five high activity binding
      peptides (HABPs) were identified; 26201, 26202, 26203 and 26204 spanned residues
      461C-K540 within RAP1 Cys region, whilst 26188 (201T-Y220) was located in p67
      amino terminal. The results showed that peptide binding was saturable, some HABPs
      inhibited in vitro merozoite invasion and specifically bound to a 72 kDa protein
      in red blood cell membrane. HABP possible function in merozoite invasion of
      erythrocytes is also discussed.

PMID- 15161084
TI  - A single dose of killed Mycobacterium bovis BCG in a novel class of adjuvant
      (Novasome) protects guinea pigs from lethal tuberculosis.
AB  - The only vaccine currently available for the prevention of tuberculosis in man is
      a live attenuated vaccine, bacille Calmette-Guerin (BCG), derived from
      Mycobacterium bovis. Concerns over the lack of the universal efficacy and safety
      of BCG have resulted in efforts to develop a new generation of TB vaccines.
      Historically, killed whole-cell preparations of mycobacteria have been
      ineffective vaccines. We revisited the potential of killed whole-cell vaccines by
      comparing their efficacy with live BCG Pasteur in a guinea pig challenge model.
      BCG Pasteur was inactivated with a low concentration of formalin and showed to be
      non-viable in culture or severe combined immunodeficient mice. Formalin
      inactivated BCG was mixed with non-phospholipid liposome adjuvants (Novasomes)
      and administered to guinea pigs as a single subcutaneous inoculation. All
      formulations were well tolerated and one conferred a significant survival
      advantage against lethal aerogenic challenge with M. bovis.

PMID- 15161085
TI  - Medicine and the Renaissance world of learning.
AB  - This article considers aspects of the relation of medicine with other learned
      disciplines during the sixteenth century and presents some examples of the
      contribution of medical authors of that period to such diverse fields as natural
      philosophy, physiognomy, alchemy, travel writing, the art of memory, and the
      study of antiquities.

PMID- 15161087
TI  - The rise and decline of the medical member: doctors and Parliament in Edwardian
      and interwar Britain.
AB  - This paper challenges the view that British medical parliamentarians were a rare
      breed whose limited presence was felt most during the late-Victorian period.
      Focused on the interwar "movement" for a medical lobby in Parliament, it
      idenitifies 159 medical candidates (of whom 72 were elected). It traces the
      motivations of the British Medical Association in promoting this movement, and
      shows how the BMA's goals were subverted in part by the identity interests and
      agendas of the medical men and women who sought election. The paper also
      highlights some of the alternative political strategies that the profession
      attempted to use to promote its interests. In addition to providing a window on
      the culture and politics of British medicine in the interwar period, it explains
      why the place of doctors in the House of Commons cannot be seen as contributing
      to the emergence of professional society as defined by Harold Perkin.

PMID- 15161086
TI  - Demonology, neurology, and medicine in Edwardian Britain.
AB  - The idea of a conflict between demonology and psychiatry has been a foundational
      myth in the history of medicine. Nineteenth-century alienists such as J.-M.
      Charcot and Henry Maudsley developed critiques of supernatural phenomena in an
      attempt to pathologize religious experience. Modern historians have reanalyzed
      these critiques, representing them as strategies in medical professionalization.
      These accounts all maintain an oddly bifurcated approach to the perceived
      conflict, treating demonology, as a passive and unchanging set of practices,
      while medicine is depicted as an active and aggressive agent. An examination of
      early twentieth-century demonological literature reveals a very different story.
      Fundamentalists and Pentecostalists engaged with the problems of conversion and
      possession, developing sophisticated models of the normal and the pathological in
      spiritual experience. Their writings drew upon medical and psychiatric sources
      ranging widely from Pastorian germ theory to Jacksonian neurology. This article
      explores the points of contact between the medical and demonological communities
      in order to demonstrate the contested nature of biomedical innovation.

PMID- 15161088
TI  - Epidemic encephalitis and American neurology, 1919-1940.
AB  - Encephalitis lethargica, also known as epidemic encephalitis, emerged as a new
      infectious disease near the end of the First World War. Bacteriologic,
      epidemiologic, and clinical investigation produced no clear consensus regarding
      the nature of the disease, even as several other experimentally demonstrable
      "encephalitides" appeared on the scene. By 1940, new encephalitis lethargica
      cases had almost entirely disappeared, and neurologists renamed this once-novel
      infection as an amorphous syndrome of marginal interest. A variety of forces
      influencing the fate of encephalitis lethargica's epidemic status can be seen at
      work in the Matheson Commission, whose members hoped to use encephalitis as a
      model disease that might supplant their reliance on clinical phenomenology with a
      causal analysis of nervous disease grounded in the laboratory. When it failed to
      live up to these expectations, the model was abandoned. Epidemic encephalitis was
      soon forgotten.

PMID- 15161089
TI  - Medical history for the masses: how American comic books celebrated heroes of
      medicine in the 1940s.
AB  - When comic books rose to mass popularity in the early 1940s, one segment of the
      industry specialized in "true adventures," with stories about real people from
      the past and the present--in contrast to competing books that offered fantasy,
      science fiction, superheroes, detectives and crime, funny people, or funny
      animals. This study examines the figures from both medical history and twentieth
      century medicine who were portrayed as heroes and role models in these comic
      books: first, to call attention to this very popular, if unknown, genre of
      medical history, and second, to illustrate how medical history was used at that
      time to popularize scientific and medical ideas, to celebrate the achievements of
      medical research, to encourage medical science as a career choice, and to show
      medicine as a humane and noble enterprise. The study explains how these medical
      history stories were situated in American popular culture more generally, and how
      the graphic power of comic books successfully conveyed both values and
      information while also telling a good story. Attention to this colorful genre of
      popular medical history enriches our picture of the mid-twentieth-century
      public's enthusiasm for medical progress.

PMID- 15161090
TI  - Theodor Kocher's surgical and clinical case presentations.
AB  - The results of an analysis of the clinical case presentations elaborated in
      manuscript by Theodor Kocher (1841-1917) in his first years as a professor at the
      University of Bern, Switzerland (1872-75), are summarized in order to indicate a
      hitherto little-known source for the history of surgery and to illustrate the
      early career of the Nobel Prize winner of 1909.

PMID- 15161091
TI  - Forum: "The unbearable heaviness of lead". Comment.

PMID- 15161093
TI  - Eki2 is upregulated specifically in the testis during mouse sex determination.
AB  - We have identified a gene with gonad restricted expression throughout mouse
      development, which is orthologous to human EKI2 (ethanolamine kinase 2). Our
      studies showed that mouse Eki2 expression became upregulated in the male gonad
      during the period of sex determination. Expression was restricted to the Sertoli
      cells of the developing testis. Eki2 has sequence similarity to ethanolamine
      (73%) and choline kinases (54%).

PMID- 15161092
TI  - Complementary expression patterns of retinoid acid-synthesizing and -metabolizing
      enzymes in pre-natal mouse inner ear structures.
AB  - Retinoic acid (RA) plays a pivotal role in patterning and differentiation of the
      embryonic inner ear. Despite its documented effects during embryonic development,
      the cellular sites that synthesize or metabolize RA in the inner ear have yet to
      be determined. Here we describe the distribution of three synthesizing enzymes,
      retinaldehyde dehydrogenases 1, 2 and 3 (RALDH1, RALDH2 and RALDH3) and two
      catabolizing enzymes (CYP26A1 and CYP26B1) in the mouse inner ear at embryonic
      day 18.5 when active cell differentiation is underway. Two detection methods,
      radioactive and non-radioactive in situ hybridization, were employed to elucidate
      the tissue distribution and cellular localization of these enzymes, respectively.
      All of the five enzymes examined, with the exception of CYP26A1, were expressed
      in both vestibular and cochlear end organs. While expression of the three RALDHs
      was observed in various cell types, CYP26B1 expression was found only in
      supporting cells of the vestibular and cochlear end organs. In the cochlea,
      expression domains of RALDH1-3 and CYP26B1 were complementary to one another.
      These results reveal specific tissue- and cellular expression patterns of RA
      synthesizing and catabolizing enzymes in the pre-natal inner ear, and suggest
      that a precise control of RA concentrations in various cell types of the inner
      ear is achieved by the balance between RALDHs and CYP26B1 activities.

PMID- 15161094
TI  - Major shifts in genomic activity accompany progression through different stages
      of the hair cycle.
AB  - Hair follicles display a unique pattern of cyclic growth and regression involving
      cell proliferation, differentiation and migration. The molecular details of these
      processes are largely unexplored. Global expression analyses on the basis of
      about 20,000 genes for each morphologically distinguishable stage of the hair
      cycle revealed unexpected complexities of and major temporal shifts in
      transcriptional programs involving about 13% of all genes. In particular,
      hundreds of genes characterise the pattern of genomic activity during regression
      and resting phases; selected genes can be used to monitor hair growth in mice. We
      demonstrate that temporal expression patterns predict gene expression domains
      within the hair follicle. Expression of insulin-like growth factor binding
      proteins and anti-angiogenic factors is associated with the regression phase of
      the hair cycle.

PMID- 15161095
TI  - Embryonic expression patterns of the Drosophila dystrophin-associated
      glycoprotein complex orthologs.
AB  - Mutations in genes encoding proteins of the human dystrophin-associated
      glycoprotein complex (DGC) cause the Duchenne, Becker and limb-girdle muscular
      dystrophies. Subsets of the DGC proteins form tissue-specific complexes which are
      thought to play structural and signaling roles in the muscle and at the
      neuromuscular junction. Furthermore, mutations in the dystrophin gene that lead
      to Duchenne muscular dystrophy are frequently associated with cognitive and
      behavioral deficits, suggesting a role for dystrophin in the nervous system.
      Despite significant progress over the past decade, many fundamental questions
      about the roles played by dystrophin and the other DGC proteins in the muscle and
      peripheral and central nervous systems remain to be answered. Mammalian models of
      DGC gene function are complicated by the existence of fully or partially
      redundant genes whose functions can mask effects of the inactivation of a given
      DGC gene. The genome of the fruitfly Drosophila melanogaster encodes a single
      ortholog of the majority of the mammalian DGC protein subclasses, thus
      potentially simplifying their functional analysis. We report here the embryonic
      mRNA expression patterns of the individual DGC orthologs. We find that they are
      predominantly expressed in the nervous system and in muscle. Dystrophin,
      dystrobrevin-like, dystroglycan-like, syntrophin-like 1, and all three
      sarcoglycan orthologs are found in the brain and the ventral nerve cord, while
      dystrophin, dystrobrevin-like, dystroglycan-like, syntrophin-like 2, sarcoglycan
      alpha and sarcoglycan delta are expressed in distinct and sometimes overlapping
      domains of mesoderm-derived tissues, i.e. muscles of the body wall and around the
      gut.

PMID- 15161096
TI  - Receptor tyrosine phosphatase zeta/beta in astrocyte progenitors in the
      developing chick spinal cord.
AB  - We cloned a cDNA encoding the receptor-type protein tyrosine phosphatase
      zeta/beta (RPTPZ/beta) from embryonic chick spinal cord. RPTPZ/beta was expressed
      throughout the ventricular zone (VZ) of the developing spinal cord and in
      scattered cells outside the VZ. Platelet-derived growth factor receptor alpha
      (PDGFRa)-positive oligodendrocyte progenitors co-expressed RPTPZ/beta within the
      VZ but down-regulated RPTPZ/beta after leaving the VZ. Most RPTPZ/beta-positive
      cells outside the VZ co-expressed glutamine synthetase and fibroblast growth
      factor receptor-3, indicating that they are astrocyte progenitors. Northern blot
      analysis revealed a single approximately 9 kbp RPTPZ/beta transcript expressed in
      the embryonic chick spinal cord, indicating that the shorter alternative-splice
      products of RPTPZ/beta found in rodent spinal cord and brain--including the
      abundant extracellular proteoglycan known as phosphacan--are not present in the
      embryonic chick spinal cord.

PMID- 15161097
TI  - Transcriptional profiling identifies genes differentially expressed during and
      after migration in murine primordial germ cells.
AB  - Mouse primordial germ cells (PGCs) are migratory until they colonize the genital
      ridges, assemble with the somatic tissue, and start to differentiate into oocytes
      or spermatogonia. Using cell transplantation experiments, we show here that germ
      cells isolated during migration (at E10.5) will migrate actively to the genital
      ridges, whereas post-migratory PGCs isolated from E12.5 embryos are non-motile
      even when transferred into a permissive environment (e.g. E10.5 host tissue).
      Major transcriptional changes must take place between E10.5 and E12.5 that
      convert germ cells from a migratory to a non-migratory state. To identify the
      genes involved, we have performed transcriptional profiling of motile and non
      motile populations of PGCs. We have identified 55 transcripts that are expressed
      in E10.5 PGCs at levels at least 3 x their expression at E12.5, and 48
      transcripts with the reciprocal expression levels. Additionally, 309 transcripts
      were found to be expressed in both populations. Many of the E10.5 transcripts
      encode proteins involved in controlling cytoskeletal and adhesive interactions
      implicated in cell motility. Many of the E12.5 transcripts encode proteins
      implicated in germ cell differentiation.

PMID- 15161098
TI  - Expression patterns of the whole troponin C gene repertoire during Drosophila
      development.
AB  - The success of the genomic sequencing programs allows the discovery of additional
      family members of genes encoding known functions. This is the case of the
      Troponin C gene repertoire in Drosophila melanogaster. We have found two new
      Troponin C genes, DmTpnC41F and DmTpnC25D, increasing to five the total number of
      Troponin C genes identified in this species. The comparative characterization of
      the five Troponin C genes in D. melanogaster demonstrates considerable variation
      in gene structure and expression pattern. Expression of one gene, DmTpnC41F, has
      more restricted tissue specificity than the rest of the TpnC genes and, with the
      chromosomically linked DmTpnC41C, is expressed specifically in the adult thorax.
      The new gene, DmTpnC25D is expressed during development more broadly than the
      rest. In adults, it is highly expressed in the adult head. Finally, the other two
      genes, DmTpnC47D and DmTpnC73F, show a high embryonic/larval expression and in
      adults are expressed almost exclusively in the abdomens. The functional adaptive
      changes that may have evolved during the expansion of this gene family are
      briefly discussed in terms of the expression patterns, gene and protein
      structures leading to a simpler, more systematic nomenclature of the gene family.

PMID- 15161099
TI  - Zebrafish beta tubulin 1 expression is limited to the nervous system throughout
      development, and in the adult brain is restricted to a subset of proliferative
      regions.
AB  - Tubulin, the building block of microtubules, consists of an alpha and beta
      subunit, each in itself a family of several highly homologous isotypes.
      Abundance, tissue specificity, developmental regulation, and possibly function
      vary between isotypes. Six isotypes of beta tubulin (class I to class VI) have
      been cloned from several vertebrate species. Class I beta tubulin is believed to
      be widely expressed, but has not been studied by in situ hybridization in any
      vertebrate species so far. We have cloned a beta tubulin from zebrafish that
      appears most similar to other vertebrate class I tubulins and name it zbeta1
      tubulin, accordingly. We report a distinct expression pattern of zbeta1 tubulin
      in the zebrafish embryo in restricted regions of the peripheral and central
      nervous system that comprise early-differentiating neurons. The expression
      pattern changes during development and in the adult zebrafish expression mostly
      is confined to a subset of proliferative zones that include the subependymal zone
      around the telencephalic ventricle, zones in the preoptic and hypothalamic area
      and in the olfactory epithelium. Thus, zbeta1 tubulin is expressed with
      remarkable selectivity during neuronal differentiation and neurogenesis in the
      embryonic and adult nervous system, respectively.

PMID- 15161100
TI  - Restricted expression domains of Ezrin in developing epithelia of the chick.
AB  - Ezrin is a member of the ERM- (Ezrin-Radixin-Moesin-) family of actin binding
      proteins, which function as linkers of the cortical cytoskeleton to components of
      the plasma membrane. Additional roles for Ezrin in intracellular signalling and
      ion channel regulation were suggested. We found Ezrin mRNA in the anterior endo-
      and mesoderm of chick gastrula stage embryos. In these tissues Ezrin message is
      strongly expressed throughout early development of the foregut (pharynx) and
      heart tube. During later stages of development, highly restricted expression
      domains of Ezrin mRNA were detected in the endodermal lining of the pharyngeal
      pouches, the mesonephric duct and tubuli, and in the ectodermal placodes giving
      rise to the inner ear, eye lens and olfactory epithelium.

PMID- 15161101
TI  - cis-Regulatory activity of randomly chosen genomic fragments from the sea urchin.
AB  - In order to determine the frequency and variety of cis-regulatory elements that
      function during embryonic development of Strongylocentrotus purpuratus, we
      constructed a GFP expression vector in which to test the activity of randomly
      chosen genomic DNA fragments that includes a promiscuous basal promoter from the
      endo16 gene. This vector was demonstrated to serve as a cis-regulatory element
      trap. We used it to carry out an initial test for the occurrence of elements that
      would promote GFP expression in this genome. In the screen reported here 108
      different randomly chosen DNA fragments (av. 3.8 kb) were inserted in the vector,
      and each was injected into > 200 zygotes. Surprisingly, 13% of the fragments
      tested yielded detectable levels of GFP expression in the recipient embryos.
      Specific patterns observed included expression in endoderm, in aboral ectoderm,
      and in pigment cells. The majority of active constructs expressed GFP in all
      spatial domains of the embryo. Elements with detectable cis-regulatory activity
      in the embryo occur in the sample screened, on the average, about every 30 kb,
      and the genome must include many thousands of such elements. On further analysis
      one isolate was shown to contain a gut specific element as well as one that
      controls expression in the secondary mesenchyme cells.

PMID- 15161102
TI  - A conserved non-homeodomain Hoxa9 isoform interacting with CBP is co-expressed
      with the 'typical' Hoxa9 protein during embryogenesis.
AB  - Various Hox genes are known to produce alternative transcripts encoding different
      isoforms whose physiological relevance during development is not yet understood.
      In this work, we analysed two different Hoxa9 mRNAs encoding a full-length
      protein (Hoxa9) or a protein lacking the homeodomain (Hoxa9T). First, we
      demonstrated that these transcripts are conserved from birds to mammals. We then
      showed that both transcripts are present throughout embryogenesis and that Hoxa9T
      transcript is particularly abundant in embryonic genital tract, kidney, forelimb
      and tail. We further found that both isoforms are able to interact with CBP,
      suggesting a competition between Hoxa9 and Hoxa9T with this protein.

PMID- 15161103
TI  - Focal adhesion kinase (FAK) expression and phosphorylation in sea urchin embryos.
AB  - We have cloned three cDNA isoforms of focal adhesion kinase (FAK) from the sea
      urchin, Lytechinus variegatus. The sea urchin FAK is more closely related to FAK
      from other deuterostomes than from invertebrate protostomes or to cell adhesion
      kinase beta (CAKbeta/Pyk2/FAK2). FAK is expressed in all cells of sea urchin
      embryos by the 120-cell stage and strongly in blastulae. Phospho-FAK concentrates
      on basal surfaces of epithelial cells in early blastulae and occurs in syncytial
      cables of primary mesenchyme cells (PMC). Inhibition of FAK by constructs of FAK
      related non-kinase delays blastocoel expansion and early PMC ingression. These
      results suggest that FAK has roles in cell adhesion and in the shape and
      integrity of the epithelial cells in sea urchin embryos.

PMID- 15161104
TI  - The rise and fall of anthropometry.

PMID- 15161106
TI  - Adverse effects of energy restriction on myogenic enzymes in judoists.
AB  - In this study, we examined the effects of weight reduction by restricting energy
      intake on muscle function and serum concentrations of myogenic enzymes in
      judoists. Twenty-seven male judoists aged 19.3 +/- 0.6 years (mean +/- s) were
      divided into three groups based on the extent of body weight reduction: high
      weight reduction (height 1.70 +/- 0.05 m, body mass 78.5 +/- 13.6 kg), low weight
      reduction (height 1.70 +/- 0.05 m, body mass 80.7 +/- 13.1 kg) and a group that
      maintained body weight while continuing to perform exercise training (height 1.78
      +/- 0.07 m, body mass 78.7 +/- 8.8 kg). Body composition, blood biochemistry,
      energy intake and anaerobic power were assessed on four occasions: 20 days
      (baseline data), 4 days and 1 day before and 7 days after competition. Compared
      with baseline, body mass and fat-free mass were significantly lower 1 day before
      competition in the high and low weight reduction groups (both P < 0.01); these
      changes persisted for 7 days after competition in the high weight reduction
      group. Serum creatine kinase was significantly elevated 1 day before competition
      in all groups (all P < 0.05), and remained higher 7 days after competition in
      both the high and low weight reduction groups. Compared with baseline, maximal
      anaerobic power was significantly lower 1 day before competition only in the high
      weight reduction group (P < 0.01). Our results suggest that energy restriction in
      addition to intense exercise training before major competition has an adverse
      effect on anaerobic power and elevates serum creatine kinase concentration,
      leading to an impairment of muscular function and an increased susceptibility of
      muscle tissue to injury.

PMID- 15161105
TI  - Sweat lactate response during cycling at 30 degrees C and 18 degrees C WBGT.
AB  - Sweat lactate reflects eccrine gland metabolism. However, the metabolic
      tendencies of eccrine glands in a hot versus thermoneutral environment are not
      well understood. Sixteen male volunteers completed a maximal cycling trial and
      two 60-min cycling trials [30 degrees C = 30 +/- 1 degrees C and 18 degrees C =
      18 +/- 1 degrees C wet bulb globe temperature (WBGT)]. The participants were
      requested to maintain a cadence of 60 rev min(-1) with the intensity
      individualized at approximately 90% of the ventilatory threshold. Sweat samples
      at 10, 20, 30, 40, 50 and 60 min were analysed for lactate concentration. Sweat
      rate at 30 degrees C (1380 +/- 325 ml x h(-1)) was significantly greater (P <
      0.05) than at 18 degrees C (632 +/- 311 ml x h(-1)). Sweat lactate concentration
      was significantly greater (P < 0.05) at each time point during the 18 degrees C
      trial, with values between trials tending to converge across time. During the 30
      degrees C trial, both heart rate (20, 30, 40, 50 and 60 min) and rectal
      temperature (30, 40, 50 and 60 min) were significantly higher than in the 18
      degrees C trial. Higher sweat lactate concentrations coupled with lower sweat
      rates may indicate a greater relative contribution of oxygen-independent
      metabolism within eccrine glands during exercise at 18 degrees C. Decreases in
      sweat lactate concentration across time suggest either greater dilution due to
      greater sweat volume or increased reliance on aerobic metabolism within eccrine
      glands. The convergence of lactate concentrations between trials may indicate
      that time-dependent modifications in sweat gland metabolism occur at different
      rates contingent partially on environmental conditions.

PMID- 15161107
TI  - Relationship between world-ranking and Olympic performance of swimmers.
AB  - Coaches believe world-ranking lists are a reliable tool for predicting
      international swimming performance. To examine the relationship between world
      ranking and Olympic performance, we modelled world-ranking time and best time
      from the 2000 Olympic Games for 407 top-50 world-ranked swimmers. Analysis of log
      transformed times yielded within-athlete and between-athlete coefficients of
      variation (CV) and percent changes in performance from world-rankings to
      Olympics. Variations and performance progressions were compared across sex,
      stroke, distance, nation and medal status. The within-athlete coefficient of
      variation of performance for all swimmers was 0.8% (95% confidence limits: 0.7 to
      0.9%). Females were slightly less consistent, although not substantially
      different to males (ratio of female/male within-athlete CV: 1.1; 95% confidence
      limits: 1.0 to 1.2) and had a wider range of talent (ratio of female/male between
      athlete CV: 1.2; 95% confidence limits: 1.1 to 1.4). Swimmers from Australia
      (AUS) were more consistent than those from the United States (USA) and other
      nations (OTHER) (ratio of within-athlete CV, USA/AUS: 1.5; 95% confidence limits:
      1.0 to 2.2; OTHER/ AUS: 1.6; 95% confidence limits: 1.2 to 2.1). Most Olympic
      medallists (87%) had a top-10 world-ranking. Overall performance time at the
      Olympics was slower than world-ranking time by 0.3% (95% confidence limits: 0.2
      to 0.4%), medallists improved by 0.6% (95% confidence limits: 0.4 to 0.9%) and
      non-medallists swam 0.6% slower (95% confidence limits: 0.5 to 0.7%). We conclude
      that a top-10 ranked swimmer who can improve performance time by 0.6%, equivalent
      to 0.13 s in the men's 50-m freestyle, will substantially increase their chance
      of an Olympic medal (the difference between first and fourth place).

PMID- 15161108
TI  - Talent identification and early development of elite water-polo players: a 2-year
      follow-up study.
AB  - The processes of talent detection and early development are critical in any sport
      programme. However, not much is known about the appropriate strategies to be
      implemented during these processes, and little scientific inquiry has been
      conducted in this area. The aim of this study was to identify variables of
      swimming, ball handling and physical ability, as well as game intelligence, which
      could assist in the selection process of young water-polo players. Twenty-four
      players aged 14-15 years underwent a battery of tests three times during a 2-year
      period, before selection to the junior national team. The tests included:
      freestyle swim for 50, 100, 200 and 400 m, 100-m breast-stroke, 100-m 'butterfly'
      (with breast-stroke leg motion), 50-m dribbling, throwing at the goal, throw for
      distance in the water, vertical 'jump' from the water, and evaluation of game
      intelligence by two coaches. A comparison of those players eventually selected to
      the team and those not selected demonstrated that, 2 years before selection,
      selected players were already superior on most of the swim tasks (with the
      exception of breast-stroke and 50-m freestyle), as well as dribbling and game
      intelligence. This superiority was maintained throughout the 2 years. Two-way
      tabulation revealed that, based on baseline scores, the prediction for 67% of the
      players was in agreement with the final selection to the junior national team. We
      recommend that fewer swim events be used in the process of selecting young water
      polo players, and that greater emphasis should be placed on evaluation of game
      intelligence.

PMID- 15161109
TI  - Knee angular displacement and extensor muscle activity in telemark skiing and in
      ski-specific strength exercises.
AB  - Much of the training of competitive telemark skiers is performed as dry-land
      exercises. The specificity of these exercises is important for optimizing the
      training effect. Our aim here was to study the activation of the knee extensor
      musculature and knee angular displacement during competitive telemark skiing and
      during dry-land strength training exercises to determine the specificity of the
      latter. Specificity was analysed with respect to angular amplitude, angular
      velocity, muscle action and electromyographic (EMG) activity. Five male telemark
      skiers of national and international standard volunteered to participate in the
      study, which consisted of two parts: (1) skiing a telemark ski course and (2)
      specific dry-land strength training exercises for telemark skiing (telemark jumps
      and barbell squats). The angular displacement of the right knee joint was
      recorded with an electrogoniometer. A tape pressure sensor was used to measure
      pressure between the sole of the foot and the bottom of the right ski boot.
      Electromyographic activity in the right vastus lateralis was recorded with
      surface electrodes. The EMG activity recorded during maximum countermovement
      jumps was used to normalize the EMG activity during telemark skiing, telemark
      jumps and barbell squats. The results showed that knee angular displacement
      during telemark skiing and dry-land telemark jumps had four distinct phases: a
      flexion (F1) and extension (E1) phase during the thrust phase of the outside
      ski/leg in the turn/jump and a flexion (F2) and extension (E2) phase when the leg
      was on the inside of the turn/jump. The vastus lateralis muscle was activated
      during F1 and E1 in the thrust phase during telemark skiing and telemark jumps.
      The overall net knee angular amplitude was significantly greater (P < 0.05) for
      telemark jumps than for telemark skiing. Barbell squats showed a knee angular
      amplitude significantly greater than that in telemark skiing (P < 0.05). The mean
      knee angular velocity of the F1 and E1 phases during telemark skiing was about
      0.47 rad x s(-1); during barbell squats, it was about 1.22 rad x s(-1). The
      angular velocity during telemark jumps was 2.34 and 1.59 rad x s(-1) in the F1
      and E1 phase, respectively. The normalized activation level of the EMG bursts
      during telemark skiing, telemark jumps and barbell squats was 70-80%. In
      conclusion, the muscle action and level of activation in the vastus lateralis
      during the F1 and E1 phases were similar during telemark skiing and dry-land
      exercises. However, the dry-land exercises showed a larger knee extension and
      flexion amplitude and angular velocity compared with telemark skiing. It appears
      that an adjustment of knee angular velocity during barbell squats and an
      adjustment of knee angle amplitude during both telemark jumps and barbell squats
      will improve specificity during training.

PMID- 15161110
TI  - The effects of protease supplementation on skeletal muscle function and DOMS
      following downhill running.
AB  - Protease supplementation has been shown to attenuate soft tissue injury resulting
      from intense exercise. The aim of this study was to evaluate the effects of
      protease supplementation on muscle soreness and contractile performance after
      downhill running. Ten matched pairs of male participants ran at a -10% grade for
      30 min at 80% of their predicted maximal heart rate. The participants consumed
      two protease tablets (325 mg pancreatic enzymes, 75 mg trypsin, 50 mg papain, 50
      mg bromelain, 10 mg amylase, 10 mg lipase, 10 mg lysozyme, 2 mg chymotrypisn) or
      a placebo four times a day beginning 1 day before exercise and lasting a total of
      4 days. The participants were evaluated for perceived muscle soreness of the
      front and back of the dominant leg, pressure pain threshold by dolorimetry of the
      anterior medial, anterior lateral, posterior medial and posterior lateral
      quadrants of the thigh, and knee extension/flexion torque and power. The
      experimental group demonstrated superior recovery of contractile function and
      diminished effects of delayed-onset muscle soreness after downhill running when
      compared with the placebo group. Our results indicate that protease
      supplementation may attenuate muscle soreness after downhill running. Protease
      supplementation may also facilitate muscle healing and allow for faster
      restoration of contractile function after intense exercise.

PMID- 15161111
TI  - Independence of reaction time and response force control during isometric leg
      extension.
AB  - In this study, we examined the relative control of reaction time and force in
      responses of the lower limb. Fourteen female participants (age 21.2 +/- 1.0
      years, height 1.62 +/- 0.05 m, body mass 54.1 +/- 6.1 kg; mean +/- s) were
      instructed to exert their maximal isometric one-leg extension force as quickly as
      possible in response to an auditory stimulus presented after one of 13 foreperiod
      durations, ranging from 0.5 to 10.0 s. In the 'irregular condition' each
      foreperiod was presented in random order, while in the 'regular condition' each
      foreperiod was repeated consecutively. A significant interactive effect of
      foreperiod duration and regularity on reaction time was observed (P < 0.001 in
      two-way ANOVA with repeated measures). In the irregular condition the shorter
      foreperiod induced a longer reaction time, while in the regular condition the
      shorter foreperiod induced a shorter reaction time. Peak amplitude of isometric
      force was affected only by the regularity of foreperiod and there was a
      significant variation of changes in peak force across participants; nine
      participants were shown to significantly increase peak force for the regular
      condition (P < 0.001), three to decrease it (P < 0.05) and two showed no
      difference. These results indicate the independence of reaction time and response
      force control in the lower limb motor system. Variation of changes in peak force
      across participants may be due to the different attention to the bipolar nature
      of the task requirements such as maximal force and maximal speed.

PMID- 15161112
TI  - BASES position statement on guidelines for resistance exercise in young people.

PMID- 15161113
TI  - Believe-it then PROVE-IT.

PMID- 15161114
TI  - Sex and thyroid hormone status in women with rheumatoid arthritis: are there any
      effects of menopausal state and disease activity on these hormones?
AB  - There has been considerable interest in the role of hormones in the
      aetiopathogenesis of rheumatoid arthritis (RA). In this study, we aimed to
      investigate sex and thyroid hormone conditions according to menopausal state and
      disease activation in RA women. Fifty-four women with RA were included in the
      study. Age-matched 28 women with low back pain were used as controls. Sex and
      thyroid hormones were evaluated in all patients, which included the measurement
      of estradiol (E2), progesterone, follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), testosterone, thyroid-stimulating hormone (TSH), total (T) and free
      (F) triiodothyronine (T3) and (T) and (F) thyroxine (T4). The RA patients were
      subdivided according to their pre-menopausal and post-menopausal status and their
      disease activation conditions. Mean age was 45.68 (+/-12.5) in women (aged 22-70)
      with RA and 42.39 (+/-12.45) in controls (aged 22-62). There were no significant
      differences in sex hormones, but there were statistically significant higher
      levels of TT3 and TT4 in whole women with RA compared to controls. Lower
      concentrations of FSH were detected in active RA patients. There were
      statistically lower concentrations of LH and higher concentrations of TT3 and TT4
      in pre-menopausal RA women, while lower concentrations of FSH were detected in
      post-menopausal RA women. TT3 and FT3 levels of pre-menopausal RA women were
      significantly higher than post-menopausal RA women. There were no significant
      differences for all other hormones studied. In conclusion, sex and thyroid
      hormones have been influenced in women with RA. Reproductive and menopausal
      conditions should be taken into consideration when sex and thyroid hormones
      studies are carried out in RA women.

PMID- 15161115
TI  - Prognostic significance of morphologic parameters in renal cell carcinoma.
AB  - Many morphologic parameters have been used in prognostic studies in renal cell
      carcinoma. In this study, the relationship between these parameters and prognosis
      was investigated. This study includes 75 patients who were treated with radical
      nephrectomy between 1985 and 2001. Pathological stage (TNM), grade (Fuhrman
      nuclear grade) cell type (UICC and AJCC), histologic pattern, tumour size,
      vascular invasion and multifocality were used as prognostic parameters. There
      were 34 female and 41 male patients with mean age of 54.5 +/- 12.5. The mean size
      of the tumour was 76.9 +/- 37.2 (30-200) mm. Of the patients, 40 had pT1, 21 pT2,
      nine pT3 and two pT4 diseases. Twenty-eight patients had Grade 1, 29 Grade 2, 15
      Grade 3 and three Grade 4 tumour. According to cell type, 63 had clear cell, six
      papillary and six undifferentiated types. Five had multifocal and seven had
      vascular invasion. In conclusion, nuclear grade and tumour stage were found as
      the most important prognostic indicators.

PMID- 15161116
TI  - Long-term outcome of carpal tunnel syndrome after conservative treatment.
AB  - The purpose of this study was to investigate the long-term prognosis of patients
      with carpal tunnel syndrome (CTS). We prospectively followed-up patients with CTS
      for 80 weeks. Thirty cases had been treated with a single injection of
      methylprednisolone acetate and another 30 with a 10-day course of prednisolone.
      At the end of the follow-up period, there were no significant differences in
      symptoms as measured by global symptom score and in the proportion of patients
      who progressed to decompressive surgery. Few patients who were not operated on
      (11.4%) remain asymptomatic.

PMID- 15161117
TI  - Efficacy and tolerability of lumiracoxib in the treatment of primary
      dysmenorrhoea.
AB  - Two randomised, multicentre, double-blind, placebo- and active-controlled, 3-way
      crossover studies were performed to evaluate the efficacy and tolerability of the
      novel COX-2 selective inhibitor lumiracoxib in the treatment of primary
      dysmenorrhoea. Subjects with moderate-to-severe dysmenorrhoea received
      lumiracoxib 400 mg once daily (od), rofecoxib 50 mg od and placebo (Study 1; n =
      84) or lumiracoxib 400 mg od, naproxen 500 mg twice daily and placebo (Study 2; n
      = 99). For the primary variable, summed pain intensity difference from 0 to 8 h
      on day 1 (SPID-8), all active treatments were superior to placebo in each study
      (p < 0.001); lumiracoxib was comparable to rofecoxib and naproxen. For PID
      (categorical scale), all active treatments were significantly better than placebo
      from 2 to 12 h; lumiracoxib was generally comparable to rofecoxib and naproxen.
      All treatments were well tolerated. Lumiracoxib 400 mg is effective and well
      tolerated in the treatment of primary dysmenorrhoea, with efficacy comparable to
      rofecoxib and naproxen.

PMID- 15161118
TI  - Rivastigmine superior to aspirin plus nimodipine in subcortical vascular
      dementia: an open, 16-month, comparative study.
AB  - Recent data indicate that patients with vascular dementia (VaD) show a
      cholinergic deficit. Having obtained good results in a previous study comparing
      rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholine
      sterase (BuChE), vs. aspirin, we aimed to compare the efficacy and tolerability
      of rivastigmine vs. aspirin plus nimodipine. Patients with a diagnosis of
      dementia and probable VaD received rivastigmine 3-6 mg/day (n = 32) or aspirin
      plus nimodipine (n = 32) in an open study for 16 months. Patients treated with
      rivastigmine showed superior benefits, compared with those receiving aspirin plus
      nimodipine, in attention, executive function, instrumental activities of daily
      living, and behavioural and psychotic disturbances. Side-effects in both groups
      were tolerable and there were no study withdrawals. The benefits observed with
      rivastigmine may reflect its inhibitory effects on AChE and BuChE, and the drug's
      affinity for frontal brain areas.

PMID- 15161119
TI  - Prevalence of right ventricular myocardial infarction in patients with acute
      inferior wall myocardial infarction.
AB  - The objective was to evaluate the prevalence of right ventricular myocardial
      infarction (RVMI) in patients with acute inferior wall myocardial infarction
      (IWMI) admitted to the National Institute of Cardiovascular Diseases, Karachi,
      Pakistan. Between August 2000 and May 2001, a total of 100 patients with acute
      IWMI were enrolled. History of all patients was taken, and thorough clinical
      examination was performed to asses the presence of signs of right ventricular
      infarction. Standard 12-lead electrocardiogram was recorded immediately on
      arrival of patients along with right precordial leads. All patients were
      considered for thrombolytic therapy in the absence of any contraindication and
      were managed with standard treatment strategies. Complications arising during the
      course of admission were recorded and compared between the two groups. There were
      86 (86%) males and 14 (14%) females. Mean age was 56.3 +/- 13.13 years (range 33
      83 years). The prevalence of RVMI in IWMI was 34%. Smoking and diabetes were more
      prevalent in RVMI group, while hypertension and family history of ischemic heart
      disease were more common in isolated IWMI. Ninety per cent of patients received
      thrombolytic therapy. In-hospital mortality (23.5%) was higher in RVMI group than
      isolated IWMI (18.1%). Other major complications were also higher in RVMI group
      than isolated IWMI. Right ventricular infarction was found in approximately one
      third of IWMI. Right ventricular infarction was associated with considerable
      morbidity and mortality, and its presence defines a higher risk subgroup of
      patients with inferior wall left ventricular infarction.

PMID- 15161120
TI  - Sexual dysfunction and diabetes.
AB  - Erectile Dysfunction (ED) is common in men with diabetes. Diabetic men are three
      times as likely to develop ED as non-diabetic men. The cause is multifactorial,
      but most commonly reflects endothelial dysfunction and autonomic neuropathy.
      Diabetes and vascular disease often coexist and ED may be a marker for silent
      occlusive arterial disease, for which the patient should be screened. Many men
      still do not volunteer their problem, hence, routine questioning by health care
      professionals is an important part of the overall management because of the
      deleterious effect of ED on relationships, self-esteem and quality of life.
      Treatment is effective in the majority and all options should be considered,
      beginning with the much preferred oral phosphodiesterase type 5 inhibitors
      (sildenafil, tadalafil, vardenafil). Female Sexual Dysfunction or Disorder (FSD)
      is more difficult to define and specific studies in diabetics are limited.
      Problems with arousal, lubrication and orgasmic dysfunction occur, but the
      fatigue of diabetes may be influencing these complaints, and in general,
      psychological issues appear to predominate.

PMID- 15161121
TI  - A review of peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy is a rare form of cardiomyopathy, of unknown aetiology,
      which is associated with a significant morbidity and mortality. It is
      characterised by the presentation of heart failure, within a month of delivery
      and up to 5 months post-partum, secondary to left ventricular impairment. It is
      essentially a diagnosis of exclusion and can only be made in the absence of any
      other demonstrable cause. One of the most challenging areas is in pre-natal
      counselling, when a woman wishes to undertake a further pregnancy, because
      recovery of left ventricular function gives no guarantee of safety.

PMID- 15161122
TI  - Nocturia in older people: a review of causes, consequences, assessment and
      management.
AB  - Nocturia is common in older people and it may be bothersome for both patients and
      carers. It is most commonly related to bladder storage difficulties and nocturnal
      polyuria. The former results most frequently from an uninhibited overactive
      bladder. The latter occurs as a consequence of age-associated changes in the
      circadian rhythm of urine excretion. The management of an overactive bladder
      includes both behavioural and drug treatment. The management options for
      nocturnal polyuria include an afternoon diuretic and desmopressin, but caution is
      required, particularly with the latter, as it can cause significant
      hyponatraemia.

PMID- 15161123
TI  - Update in the pharmaceutical therapy of the irritable bowel syndrome.
AB  - The therapeutic management of the irritable bowel syndrome (IBS) is ineffective
      and not satisfying either patients or practitioners. Research in functions of the
      enteric nervous system and its interaction with the central nervous system is the
      basis for the development of emerging pharmaceuticals in therapy of the IBS.
      These pharmaceuticals include agents such as opioid agonists, psychotropic agents
      and particularly serotonin receptor modulators. These novel pharmaceuticals aim
      to provide a more comprehensive approach in the therapy of the IBS and will serve
      both patients and practitioners. So far, the US Food and Drug Administration has
      approved two agents specifically for the treatment of the IBS, both belonging to
      the group of serotonin receptor modulators. However, questions remain whether a
      single therapy is sufficient in the management of IBS because this disease is
      influenced by biological and psychological as well as cultural and social
      factors.

PMID- 15161124
TI  - Management of prostate-specific antigen relapse in prostate cancer: a European
      Consensus.
AB  - A European Consensus on the management of prostate-specific antigen (PSA) relapse
      in patients with prostate cancer has been formulated. The key recommendations
      proposed are that total PSA is the best detection tool for prostate cancer, with
      free and complexed PSA having a role in the PSA range 1-4 ng/ml. PSA relapse
      after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with
      one subsequent rise, while the ASTRO definition should be used after
      radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be
      considered an indicator of a positive response. Continuous assessment using
      nomograms or artificial neural networks will help to determine whether
      progression after local therapy is distant or local, which is the basis for
      treatment decisions. Secondary treatment after local failure of RP should be
      initiated when PSA levels reach 1.0-1.5 ng/ml and salvage radiotherapy can be
      considered with or without hormonal therapy. Local failure after radiotherapy can
      be treated with a choice of high-intensity-focused ultrasound, salvage RP (only
      in highly selected patients), cryotherapy or external beam radiation. Treatment
      of distant failure involves hormonal manipulation, the type and the timing of
      which is based on both physician and patient preferences.

PMID- 15161125
TI  - Carbohydrate-deficient transferrin: a marker of alcohol abuse.
AB  - Serum carbohydrate-deficient transferrin (CDT) measurement is valuable for the
      identification of chronic excess alcohol consumption. CDT is increased in serum
      in approximately 50% of those classed as heavy drinkers and 70-80% of those
      defined as alcoholics. With abstinence, the serum CDT concentration reverts
      towards normal within approximately 2 weeks. Specificity for alcohol abuse ranges
      from 80 to 95% in the general population and from 70 to 80% in liver clinic
      patients.

PMID- 15161126
TI  - Exubera inhaled insulin: a review.
AB  - The focus of this review is inhaled insulin, specifically Exubera, which
      represents a novel prandial insulin delivery method. Fear of hypoglycaemia and
      the reluctance of patients to use multiple daily injection regimens is a major
      barrier to achieving good glycaemic control in patients with type 1 and type 2
      diabetes. Inhaled insulin has been developed to provide more physiological
      prandial insulin replacement than regular human insulin in patients with
      diabetes, with the advantage of non-invasive delivery. Good glycaemic control,
      comparable to modern subcutaneously administered insulin preparations, has
      already been demonstrated, and no unexpected safety concerns have been reported
      with inhaled insulin. The development of such insulin delivery technologies that
      are better tailored to patients' needs may improve patient compliance, thereby
      facilitating the attainment of treatment targets. This review summarises the
      studies available and discusses the potential implications to patients of needle
      free insulin administration.

PMID- 15161127
TI  - Clopidogrel in the management of cerebrovascular events.
AB  - The inhibition of platelet function has proved its effectiveness in the reduction
      of vascular events in many large trials for many different compounds such as ASA,
      ticlopinin, dipyridamole or clopidogrel. In this overview, the authors analyse
      the results of recent trials and present ongoing or future trials with
      clopidogrel. Clopidogrel has proved its superiority in prevention of vascular
      events as compared to ASA, being even higher in high-risk groups such as diabetic
      patients. For the post-interventional treatment of patients undergoing stent
      protected dilatation of coronary arteries, the combination of ASA and clopidogrel
      has become a standard procedure. There is also evidence that the combination of
      ASA and Clopidogrel is better than ASA alone in long-term treatment up to at
      least 9 months. The long-term combination therapy seems to be very promising and
      is currently analysed in three large trials in over 30,000 patients with a large
      number of stroke patients. These trials will also answer the question, whether
      the combination therapy is safe in long-term secondary stroke prevention.
      However, there is still a widespread reluctance in doctors to prescribe
      Clopidogrel for its costs. Cost-effectiveness studies predict up to tenfold
      higher cost in the prevention of vascular events when compared to ASA, in times
      of shrinking health budgets a topic of interest.

PMID- 15161128
TI  - Diaphragmatic palsy in stroke.

PMID- 15161129
TI  - Eosinophilic gastroenteritis: presentation of two patients with unusual affect of
      terminal ileum and caecum with manifestations of acute abdomen and literature
      review.
AB  - Eosinophilic gastroenteritis is a rare disease; the long-term personal history
      with digestive symptoms and the course of the disease with relapses and
      remissions is the key for the disease to be suspected. Endoscopy, CT scan and
      sonographic studies may provide important indirect signs of the disease and in
      combination with histological examination the diagnosis can be achieved. The
      administration of corticosteroids is an important factor for the treatment or the
      remission of the disease. In this study two cases with unusual location of the
      disease, on the terminal ileum and caecum, are presented and a literature review
      is attempted. The disease process, clinical and laboratory findings as well as
      the surgical approach used are described. Eosinophilic gastroenteritis is a very
      rare disease with its surgical complications. The disease is a non-surgical
      disease, thus presurgical diagnosis is important because the entity discussed can
      be under control by conservative treatment. A high disease suspicious index must
      be kept in the physicians' mind.

PMID- 15161130
TI  - Conference report: American College of Cardiology annual scientific session (7-10
      March, New Orleans, USA).

PMID- 15161131
TI  - Delayed presentation of prosthetic joint infection due to Listeria monocytogenes.
AB  - Infection with Listeria monocytogenes is rare and has been described in
      prosthetic valves, stent grafts and prosthetic joints. The route of infection
      appears to be haematogenous. The choice between conservative treatment with
      antibiotics or surgical treatment with debridement and revision of the components
      remains controversial. The best antibiotic treatment is not known with ampicillin
      being the first choice in most cases. Prosthetic infections with Listeria
      monocytogenes usually occur in patients with malignancy, diabetes mellitus,
      chronic renal disease, liver disease, elderly patients and patients receiving
      immunosuppressive therapy. The hip is the commonest prosthetic joint affected
      followed by the knee. We report the seventh case of Listeria monocytogenes
      infection in a non-immunocompromised patient involving a prosthetic joint.

PMID- 15161132
TI  - Acute ulcerative colitis in a Meckel's diverticulum.
AB  - This report describes the case of a patient with acute ulcerative colitis who
      underwent an emergency colectomy and removal of an incidental Meckel's
      diverticulum which appeared inflamed. Histology showed acute inflammation of
      colonic epithelium within the Meckel's diverticulum, justifying its removal and
      confirming that this was indeed a 'skip lesion'.

PMID- 15161133
TI  - Submucous lipoma of the ileocaecal valve presenting as caecal volvulus.
AB  - Caecal volvulus is a well described but unusual condition. We report here, a case
      of caecal volvulus in a 53-year-old Caucasian woman associated with
      intussuscepted submucous lipoma of the ileocaecal region. The imaging and
      pathology are presented. Submucous lipoma of the ileocaecal region is uncommon
      but well described. It can be mistaken as carcinoma of the ascending colon on
      barium enema and on computed tomography scan. The combination with caecal
      volvulus is a rare occurrence.

PMID- 15161134
TI  - Intranasal schwannoma in a young woman.
AB  - A rare case of a schwannoma arising from the middle meatus in a 24-year-old woman
      is reported. The patient presented with a 12-month history of right-sided nasal
      obstruction, rhinorrhoea, anosmia, headache and recurrent minor nosebleeds.
      Examination of the right nasal cavity revealed a polypoidal mass. Computerised
      tomography showed the mass completely occluding the nasal passage with evidence
      of a secondary maxillary sinusitis. She underwent a complete intranasal excision
      of the polypoidal mass which was arising from the right middle meatus. The
      histological features of the lesion were consistent with a schwannoma including
      diffuse immunoreactivity for S-100 protein. This case illustrates the need to
      consider schwannoma, amongst many other lesions, in the differential diagnosis of
      a unilateral nasal mass and reinforces the established principle of sending all
      material removed from the nose for histological examination.

PMID- 15161135
TI  - What is OTT?

PMID- 15161136
TI  - Social learning strategies.
AB  - In most studies of social learning in animals, no attempt has been made to
      examine the nature of the strategy adopted by animals when they copy others.
      Researchers have expended considerable effort in exploring the psychological
      processes that underlie social learning and amassed extensive data banks
      recording purported social learning in the field, but the contexts under which
      animals copy others remain unexplored. Yet, theoretical models used to
      investigate the adaptive advantages of social learning lead to the conclusion
      that social learning cannot be indiscriminate and that individuals should adopt
      strategies that dictate the circumstances under which they copy others and from
      whom they learn. In this article, I discuss a number of possible strategies that
      are predicted by theoretical analyses, including copy when uncertain, copy the
      majority, and copy if better, and consider the empirical evidence in support of
      each, drawing from both the animal and human social learning literature. Reliance
      on social learning strategies may be organized hierarchically, their being
      employed by animals when unlearned and asocially learned strategies prove
      ineffective but before animals take recourse in innovation.

PMID- 15161137
TI  - Action imitation in birds.
AB  - Action imitation, once thought to be a behavior almost exclusively limited to
      humans and the great apes, surprisingly also has been found in a number of bird
      species. Because imitation has been viewed by some psychologists as a form of
      intelligent behavior, there has been interest in how it is distributed among
      animal species. Although the mechanisms responsible for action imitation are not
      clear, we are now at least beginning to understand the conditions under which it
      occurs. In this article, I try to identify and differentiate the various forms of
      socially influenced behavior (species-typical social reactions, social effects on
      motivation, social effects on perception, socially influenced learning, and
      action imitation) and explain why it is important to differentiate imitation from
      other forms of social influence. I also examine some of the variables that appear
      to be involved in the occurrence of imitation. Finally, I speculate about why a
      number of bird species, but few mammal species, appear to imitate.

PMID- 15161138
TI  - Socially biased learning in monkeys.
AB  - We review socially biased learning about food and problem solving in monkeys,
      relying especially on studies with tufted capuchin monkeys (Cebus apella) and
      callitrichid monkeys. Capuchin monkeys most effectively learn to solve a new
      problem when they can act jointly with an experienced partner in a socially
      tolerant setting and when the problem can be solved by direct action on an object
      or substrate, but they do not learn by imitation. Capuchin monkeys are motivated
      to eat foods, whether familiar or novel, when they are with others that are
      eating, regardless of what the others are eating. Thus, social bias in learning
      about foods is indirect and mediated by facilitation of feeding. In most
      respects, social biases in learning are similar in capuchins and callitrichids,
      except that callitrichids provide more specific behavioral cues to others about
      the availability and palatability of foods. Callitrichids generally are more
      tolerant toward group members and coordinate their activity in space and time
      more closely than capuchins do. These characteristics support stronger social
      biases in learning in callitrichids than in capuchins in some situations. On the
      other hand, callitrichids' more limited range of manipulative behaviors, greater
      neophobia, and greater sensitivity to the risk of predation restricts what these
      monkeys learn in comparison with capuchins. We suggest that socially biased
      learning is always the collective outcome of interacting physical, social, and
      individual factors, and that differences across populations and species in social
      bias in learning reflect variations in all these dimensions. Progress in
      understanding socially biased learning in nonhuman species will be aided by the
      development of appropriately detailed models of the richly interconnected
      processes affecting learning.

PMID- 15161139
TI  - How do apes ape?
AB  - In the wake of telling critiques of the foundations on which earlier conclusions
      were based, the last 15 years have witnessed a renaissance in the study of social
      learning in apes. As a result, we are able to review 31 experimental studies from
      this period in which social learning in chimpanzees, gorillas, and orangutans has
      been investigated. The principal question framed at the beginning of this era, Do
      apes ape? has been answered in the affirmative, at least in certain conditions.
      The more interesting question now is, thus, How do apes ape? Answering this
      question has engendered richer taxonomies of the range of social-learning
      processes at work and new methodologies to uncover them. Together, these studies
      suggest that apes ape by employing a portfolio of alternative social-learning
      processes in flexibly adaptive ways, in conjunction with nonsocial learning. We
      conclude by sketching the kind of decision tree that appears to underlie the
      deployment of these alternatives.

PMID- 15161141
TI  - Testing social learning in a wild mountain parrot, the kea (Nestor notabilis).
AB  - Huber, Taborsky, and Rechberger (2001) reported an experiment in which the
      efficiency with which captive keas opened a complex food container was increased
      by observation of a skilled conspecific. However, only testing social learning in
      free-ranging animals can demonstrate social learning in natural conditions. For
      that purpose, a tube-lifting paradigm was developed and tested on keas both in
      captivity and in Mount Cook National Park, New Zealand. The task was to remove a
      tube from an upright pole in order to gain access to a reward inside the tube.
      The top of the pole was higher than a standing kea, so that, to remove the tube,
      an individual had to simultaneously climb onto the pole and manipulate the tube
      up the pole with its bill. Because only 1 naive bird managed to remove a tube
      twice in 25 half-hour sessions and disappeared after success, another bird was
      trained to solve the task and to provide demonstrations for others. Even under
      such conditions, only 2 of at least 15 birds learned to remove the tube in 28
      sessions. There was no indication that observer birds' use of bill and feet when
      exploring the tube changed as the number of observations of tube removal
      increased in a way that would, in principle, increase the likelihood of tube
      removal. The results suggest a dissociation of social learning potential as
      assessed in laboratory animals, and social transmission of foraging techniques in
      natural populations.

PMID- 15161140
TI  - Approaches to the study of traditional behaviors of free-living animals.
AB  - I review literature on four different approaches to the study of traditions in
      animals: observation of free-living animals, laboratory experiment, armchair
      analysis, and field experiment. Because, by definition, a tradition entails
      social learning of some kind, it is difficult, perhaps impossible, to establish
      that a behavior is in fact traditional without knowledge of how it develops.
      Observations of free-living animals often provide strong circumstantial evidence
      of a tradition. However, even in the view of several researchers who have studied
      possibly traditional behaviors in natural populations, observation alone has not
      proven sufficient to show that social learning contributes to development of
      behaviors of interest. The relevance of laboratory experiments to the
      understanding of the development of behaviors in free-living animals is always
      open to challenge. Armchair analyses of field data can produce interesting
      hypotheses but cannot test them. Field experiments to determine how behaviors of
      interest develop in population members provide a promising way forward.

PMID- 15161142
TI  - Development, direction, and damage limitation: social learning in domestic fowl.
AB  - This review highlights two areas of particular interest in the study of social
      learning in fowl. First, the role of social learning in the development of
      feeding and foraging behavior in young chicks and older birds is described. The
      role of the hen as a demonstrator and possible teacher is considered, and the
      subsequent social influence of brood mates and other companions on food avoidance
      and food preference learning is discussed. Second, the way in which work on
      domestic fowl has contributed to an understanding of the importance of directed
      social learning is examined. The well-characterized hierarchical social
      organization of small chicken flocks has been used to design studies which
      demonstrate that the probability of social transmission is strongly influenced by
      social relationships between birds. The practical implications of understanding
      the role of social learning in the spread of injurious behaviors in this
      economically important species are briefly considered.

PMID- 15161143
TI  - Social and asocial cues about new food: cue reliability influences intake in
      rats.
AB  - Dietary generalists often treat new foods with caution and may rely on social
      cues to identify new foods that are safe to eat. However, not all generalists
      show the same degree of caution, nor do they all rely on social cues to the same
      extent. The cue reliability approach (CRA) attempts to account for this variation
      by quantifying the costs and benefits of sampling a new food for the first time.
      The experiments reported here tested predictions of the CRA, and the results
      suggested that rats eat more new food when asocial cues predict that new foods
      will prove more profitable than familiar foods. The experimental results also
      suggested that rats are more likely to seek out social cues when asocial cues are
      unreliable.

PMID- 15161144
TI  - Distinguishing social and asocial learning using diffusion dynamics.
AB  - Theoretical models predict that the cumulative number of individuals displaying a
      socially learned novel behavior will follow an accelerating pattern over time,
      whereas asocial processes have been associated with linear or decelerating
      functions. This raises the possibility that the shape of the diffusion curve may
      reveal something about the learning processes involved. If true, this would be
      particularly useful for identifying social transmission in observational field
      studies. Published data are reviewed and are found to provide limited support for
      this view. The use of accelerating curves as a diagnostic is challenging because
      (1) alternative theoretical models make similar predictions, (2) clear supporting
      empirical data are lacking, and (3) practical considerations frequently make
      accurate construction of the diffusion curve difficult.

PMID- 15161146
TI  - Information and aggression in fishes.
AB  - Aggressive interactions between fishes commonly take place in a social
      environment in which uninvolved individuals (bystanders) have an opportunity to
      gather information about interactants. Signals frequently used during such
      interactions are designed to transmit information about resource-holding power
      and/or intention. They are generally related to the level of escalation reached
      and the eventual outcome of a fight. We consider here the information available
      in signaling and nonsignaling aspects of aggressive interactions. We focus, in
      particular, on information available to bystanders. We summarize evidence that
      bystanders alter their behavior toward interactants on the basis of information
      acquired while bystanding, and we discuss the sources of information that may
      result in this change of behavior. In particular, we distinguish eavesdropping
      (i.e., extracting information from signaling interactions) as a subset of
      bystanding (i.e., extracting information from all available sources). We conclude
      that considerations of aggressive strategies should include potential costs and
      benefits resulting from wider social contexts in which aggression occurs.

PMID- 15161147
TI  - Social transmission of courtship behavior and mating preferences in brown-headed
      cowbirds, Molothrus ater.
AB  - Studies of the social learning of courtship behaviors and mating preferences of
      brown-headed cowbirds (Molothrus ater) are reviewed. Earlier work has suggested
      that cowbirds from behaviorally distinct populations mate preferentially with
      others from the same population. Studies are described which indicate that
      patterns of courtship behavior that differ by population can be socially
      transmitted across generations are described. Social background affects male
      songs, female preferences for males as mates, and courtship interactions between
      females and males. Thus, social traditions influence mating decisions and may,
      ultimately, impact reproductive success in this species. Recent work on possible
      social mechanisms involved in the ontogeny of courtship behavior is described.
      The implications of these findings are discussed, and future research directions
      are suggested.

PMID- 15161145
TI  - Influences of social learning on mate-choice decisions.
AB  - Evidence from both field and laboratory is consistent with the hypothesis that
      animals can acquire mate preferences by observing the mating behavior of others.
      It is difficult, however, to distinguish social learning about mates from a host
      of other social effects on mating that do not produce changes in preferences.
      Examples are drawn from laboratory studies on mate choice in female and male
      Japanese quail that illustrate ways in which social cues influence mating
      decisions. Quail of both sexes use social cues to modify their mate choices, but
      the sexes use the information to serve different purposes. Female quail gain
      preferences for males seen mating with other females, whereas males avoid females
      that they had observed mating with other males. This sex difference in social
      learning provides an example of how costs and benefits of sexual behavior can
      shape decision-making processes. Implications of the influence of social learning
      on sexual selection are briefly discussed.

PMID- 15161149
TI  - Management of a coastal aquifer.

PMID- 15161148
TI  - Social learning about predators: a review and prospectus.
AB  - In comparison with social learning about food, social learning about predators
      has received little attention. Yet such research is of potential interest to
      students of animal cognition and conservation biologists. I summarize evidence
      for social learning about predators by fish, birds, eutherian mammals, and
      marsupials. I consider the proposal that this phenomenon is a case of S-S
      classical conditioning and suggest that evolution may have modified some of the
      properties of learning to accommodate for the requirements of learning socially
      about danger. I discuss some between-species differences in the properties of
      socially acquired predator avoidance and suggest that learning may be faster and
      more robust in species in which alarm behavior reliably predicts high predatory
      threat. Finally, I highlight how studies of socially acquired predator avoidance
      can inform the design of prerelease antipredator training programs for endangered
      species.

PMID- 15161150
TI  - Push-pull tests for assessing in situ aerobic cometabolism.
AB  - Three types of single-well push-pull tests were developed for use in assessing
      the feasibility of in situ aerobic cometabolism of chlorinated aliphatic
      hydrocarbons (CAHs). These included transport tests, biostimulation tests, and
      activity tests. Transport tests are conducted to evaluate the mobility of solutes
      used in subsequent tests. These included bromide or chloride (conservative
      tracers), propane (growth substrate), ethylene, propylene (CAH surrogates),
      dissolved oxygen (electron acceptor), and nitrate (a minor nutrient). Tests were
      conducted at an experimental wellfield of Oregon State University. At this site,
      extraction phase breakthrough curves for all solutes were similar, indicating
      apparent conservative transport of the dissolved gases and nitrate prior to
      biostimulation. Biostimulation tests were conducted to stimulate propane
      utilizing activity of indigenous microorganisms and consisted of sequential
      injections of site ground water containing dissolved propane and oxygen.
      Biostimulation was detected by the increase in rates of propane and oxygen
      utilization after each injection. Activity tests were conducted to quantify rates
      of substrate utilization and to confirm that CAH-transforming activity had likely
      been stimulated. In particular, the transformation of injected CAH surrogates
      ethylene and propylene to the cometabolic byproducts ethylene oxide and propylene
      oxide provided evidence that activity of the monooxygenase enzyme system,
      responsible for aerobic cometabolic transformations of CAHs, had likely also been
      stimulated. Estimated zero-order transformation rates decreased in the order
      propane > ethylene > propylene. The series of push-pull tests developed and field
      tested in this study should prove useful for conducting rapid, low-cost
      feasibility assessments for in situ aerobic cometabolism of CAHs.

PMID- 15161151
TI  - Conduit properties and karstification in the unconfined Floridan aquifer.
AB  - Exchange of water between conduits and matrix is an important control on regional
      chemical compositions, karstification, and quality of ground water resources in
      karst aquifers. A sinking stream (Santa Fe River Sink) and its resurgence (River
      Rise) in the unconfined portion of the Floridan Aquifer provide the opportunity
      to monitor conduit inflow and outflow. The use of temperature as a tracer allows
      determination of residence times and velocities through the conduit system. Based
      on temperature records from two high water events, flow is reasonably represented
      as pipe flow with a cross-sectional area of 380 m2, although this model may be
      complicated by losses of water from the conduit system at higher discharge rates.
      Over the course of the study year, the River Rise discharged a total of 1.9 x
      10(7) m3 more water than entered the River Sink, reflecting net contribution of
      ground water from the matrix into the conduit system. However, as River Sink
      discharge rates peaked following three rainfall events during the study period,
      the conduit system lost water, presumably into the matrix. Surface water in high
      flow events is typically undersaturated with respect to calcite and thus may lead
      to dissolution, depending on its residence time in the matrix. A calculation of
      local denudation is larger than other regional estimates, perhaps reflecting
      return of water to conduits before calcite equilibrium is reached. The exchange
      of matrix and conduit water is an important variable in karst hydrology that
      should be considered in management of these water resources.

PMID- 15161152
TI  - A methodology for validating numerical ground water models.
AB  - Ground water validation is one of the most challenging issues facing modelers and
      hydrogeologists. Increased complexity in ground water models has created a gap
      between model predictions and the ability to validate or build confidence in
      predictions. Specific procedures and tests that can be easily adapted and applied
      to determine the validity of site-specific ground water models do not exist. This
      is true for both deterministic and stochastic models, with stochastic models
      posing the more difficult validation problem. The objective of this paper is to
      propose a general validation approach that addresses important issues recognized
      in previous validation studies, conferences, and symposia. The proposed method
      links the processes for building, calibrating, evaluating, and validating models
      in an iterative loop. The approach focuses on using collected validation data to
      reduce uncertainty in the model and narrow the range of possible outcomes. This
      method is designed for stochastic numerical models utilizing Monte Carlo
      simulation approaches, but it can be easily adapted for deterministic models. The
      proposed methodology relies on the premise that absolute validity is not
      theoretically possible, nor is it a regulatory requirement. Rather, the proposed
      methodology highlights the importance of testing various aspects of the model and
      using diverse statistical tools for rigorous checking and confidence building in
      the model and its predictions. It is this confidence that will encourage
      regulators and the public to accept decisions based on the model predictions.
      This validation approach will be applied to a model, described in this paper,
      dealing with an underground nuclear test site in rural Nevada.

PMID- 15161153
TI  - Magnetic resonance sounding applied to aquifer characterization.
AB  - Magnetic resonance sounding (MRS) is distinguished from other geophysical tools
      used for ground water investigation by the fact that it measures a magnetic
      resonance signal generated directly from subsurface water molecules. An
      alternating current pulse energizes a wire loop on the ground surface and the MRS
      signal is generated; subsurface water is indicated, with a high degree of
      reliability, by nonzero amplitude readings. Measurements with varied pulse
      magnitudes then reveal the depth and thickness of water saturated layers. The
      hydraulic conductivity of aquifers can also be estimated using boreholes for
      calibration. MRS can be used for both predicting the yield of water supply wells
      and for interpolation between boreholes, thereby reducing the number of holes
      required for hydrogeological modeling. An example of the practical application of
      MRS combined with two-dimensional electrical imaging, in the Kerbernez and Kerien
      catchments area of France, demonstrates the efficiency of the technique.

PMID- 15161154
TI  - Spatial variability of in situ microbial activity: biotracer tests.
AB  - Biotracer tests have been proposed as a means by which to characterize the in
      situ biodegradation potential for field-scale systems. In this study, field
      experiments were conducted at two sites to evaluate the utility of the biotracer
      method for characterizing the spatial variability of microbial activity. The
      first site is a mixed waste-contaminated surficial aquifer in Utah, and the
      second site is a chlorinated solvent-contaminated regional aquifer in Tucson,
      Arizona. Mass recovery of the biotracer decreased approximately linearly with
      increasing residence time for the Tucson site. Similar behavior was observed at
      the Utah site, except in the region adjacent to the injection zone, where percent
      recoveries were much lower than those predicted using a correlation determined
      using data collected downgradient of the injection zone. First-order
      biodegradation rate coefficients obtained from model calibration of the tracer
      data varied between 0.2 and 0.5/day for the Tucson site. For the Utah site, the
      values varied between 0.1 and 0.6/day downgradient of the injection wells, and
      between 0.7 and 2.6/day near the injection wells. Considering the large range
      over which biodegradation rate coefficients can vary, the rate coefficient
      exhibited relatively minimal spatial variability (factor of 2.5) for the Tucson
      site. Conversely, the spatial variability of the rate coefficient was an order of
      magnitude greater for the Utah site. These differences in variability are
      consistent with conditions associated with the respective sites. For example, the
      greater microbial activity observed in the vicinity of the injection wells for
      the Utah site is consistent with the biomass distribution determined from
      analysis of core samples, which shows larger bacterial cell densities for the
      region near the injection wells. These results illustrate the utility of
      biotracer tests for in situ characterization of microbial activity (e.g.,
      biodegradation potential), including evaluation of potential spatial variability.

PMID- 15161155
TI  - Estrogen in a karstic aquifer.
AB  - Adverse impacts on the health of some fish populations, such as skewed sex
      distributions, have been noted in surface waters and in laboratory experiments
      with relatively low concentrations (above 25 ng/L) of natural estrogen (17 beta
      estradiol--E2). Sources of E2 to surface and ground waters can include avian,
      human, and mammalian waste products. The Ozark Plateau Aquifer (OPA) is a karstic
      basin that receives a significant portion of its water through losing reaches of
      rivers. Thus, there is a direct connection between surface water and ground
      water. The OPA was targeted for an E2 study to assess the potential for adverse
      health effects to aquatic organisms living in the system. Eight springs, which
      drain the aquifer, were sampled quarterly. The concentrations of E2 in the OPA
      ranged from 13 to 80 ng/L. For any one sampling event, the concentrations of E2
      at the spring waters were statistically similar; however, the concentrations of
      E2 at all springs varied throughout the year. At Maramec Spring, one of the
      larger springs, the E2 concentration, was correlated with discharge. Based on the
      correlation between discharge and E2 concentration, aquatic organisms living in
      the plateau or in its discharged waters, including the threatened southern
      cavefish T. subterraneus, are exposed to concentration of E2 above 25 ng/L
      approximately 60% of the time. This implies that organisms living in karst basins
      throughout the OPA are likely exposed to E2 concentrations that may adversely
      impact their reproductive success for a significant portion of each year.

PMID- 15161156
TI  - Effects of model sensitivity and nonlinearity on nonlinear regression of ground
      water flow.
AB  - Nonlinear regression is increasingly applied to the calibration of hydrologic
      models through the use of perturbation methods to compute the Jacobian or
      sensitivity matrix required by the Gauss-Newton optimization method.
      Sensitivities obtained by perturbation methods can be less accurate than those
      obtained by direct differentiation, however, and concern has arisen that the
      optimal parameter values and the associated parameter covariance matrix computed
      by perturbation could also be less accurate. Sensitivities computed by both
      perturbation and direct differentiation were applied in nonlinear regression
      calibration of seven ground water flow models. The two methods gave virtually
      identical optimum parameter values and covariances for the three models that were
      relatively linear and two of the models that were relatively nonlinear, but gave
      widely differing results for two other nonlinear models. The perturbation method
      performed better than direct differentiation in some regressions with the
      nonlinear models, apparently because approximate sensitivities computed for an
      interval yielded better search directions than did more accurately computed
      sensitivities for a point. The method selected to avoid overshooting minima on
      the error surface when updating parameter values with the Gauss-Newton procedure
      appears for nonlinear models to be more important than the method of sensitivity
      calculation in controlling regression convergence.

PMID- 15161157
TI  - Ground water discharge and nitrate flux to the Gulf of Mexico.
AB  - Ground water samples (37 to 186 m depth) from Baldwin County, Alabama, are used
      to define the hydrogeology of Gulf coastal aquifers and calculate the subsurface
      discharge of nutrients to the Gulf of Mexico. The ground water flow and nitrate
      flux have been determined by linking ground water concentrations to 3H/3He and
      4He age dates. The middle aquifer (A2) is an active flow system characterized by
      postnuclear tritium levels, moderate vertical velocities, and high nitrate
      concentrations. Ground water discharge could be an unaccounted source for
      nutrients in the coastal oceans. The aquifers annually discharge 1.1 +/- 0.01 x
      10(8) moles of nitrate to the Gulf of Mexico, or 50% and 0.8% of the annual
      contributions from the Mobile-Alabama River System and the Mississippi River
      System, respectively. In southern Baldwin County, south of Loxley, increasing
      reliance on ground water in the deeper A3 aquifer requires accurate estimates of
      safe ground water withdrawal. This aquifer, partially confined by Pliocene clay
      above and Pensacola Clay below, is tritium dead and contains elevated 4He
      concentrations with no nitrate and estimated ground water ages from 100 to 7000
      years. The isotopic composition and concentration of natural gas diffusing from
      the Pensacola Clay into the A3 aquifer aids in defining the deep ground water
      discharge. The highest 4He and CH4 concentrations are found only in the deepest
      sample (Gulf State Park), indicating that ground water flow into the Gulf of
      Mexico suppresses the natural gas plume. Using the shape of the CH4-He plume and
      the accumulation of 4He rate (2.2 +/- 0.8 microcc/kg/1000 years), we estimate the
      natural submarine discharge and the replenishment rate for the A3 aquifer.

PMID- 15161158
TI  - Strontium isotopic identification of water-rock interaction and ground water
      mixing.
AB  - 87Sr/86Sr ratios of ground waters in the Bighorn and Laramie basins' carbonate
      and carbonate-cemented aquifer systems, Wyoming, United States, reflect the
      distinctive strontium isotope signatures of the minerals in their respective
      aquifers. Well water samples from the Madison Aquifer (Bighorn Basin) have
      strontium isotopic ratios that match their carbonate host rocks. Casper Aquifer
      ground waters (Laramie Basin) have strontium isotopic ratios that differ from the
      bulk host rock; however, stepwise leaching of Casper Sandstone indicates that
      most of the strontium in Casper Aquifer ground waters is acquired from
      preferential dissolution of carbonate cement. Strontium isotope data from both
      Bighorn and Laramie basins, along with dye tracing experiments in the Bighorn
      Basin and tritium data from the Laramie Basin, suggest that waters in carbonate
      or carbonate-cemented aquifers acquire their strontium isotope composition very
      quickly--on the order of decades. Strontium isotopes were also used successfully
      to verify previously identified mixed Redbeds-Casper ground waters in the Laramie
      Basin. The strontium isotopic compositions of ground waters near Precambrian
      outcrops also suggest previously unrecognized mixing between Casper and
      Precambrian aquifers. These results demonstrate the utility of strontium isotopic
      ratio data in identifying ground water sources and aquifer interactions.

PMID- 15161159
TI  - Estimation of anaerobic biodegradation rate constants at MGP sites.
AB  - Field data at six former manufactured gas plant sites in New Jersey were used to
      estimate the biodegradation rate constants for the anaerobic processes naturally
      occurring within the ground water contaminant plumes (primarily iron and sulfate
      reduction). Those rate constants turned out to be about an order of magnitude
      smaller than values reported for the same contaminants (primarily benzene and
      naphthalene) at fuel sites. At four of the sites, there appeared to be sufficient
      electron acceptor present to eventually degrade the contaminants in the plume.
      However, the presence of nonaqueous phase liquids tends to offset that capacity
      by continuing to act as a source of contaminants that can dissolve in the ground
      water.

PMID- 15161160
TI  - Geochemical processes during five years of aquifer storage recovery.
AB  - A key factor in the long-term viability of aquifer storage recovery (ASR) is the
      extent of mineral solution interaction between two dissimilar water types and
      consequent impact on water quality and aquifer stability. We collected
      geochemical and isotopic data from three observation wells located 25, 65, and
      325 m from an injection well at an experimental ASR site located in a karstic,
      confined carbonate aquifer in South Australia. The experiment involved five major
      injection cycles of a total of 2.5 x 10(5) m3 of storm water (total dissolved
      solids [TDS] approximately 150 mg/L) into the brackish (TDS approximately 2400
      mg/L) aquifer. Approximately 60% of the mixture was pumped out during the fifth
      year of the experiment. The major effect on water quality within a 25 m radius of
      the injection well following injection of storm water was carbonate dissolution
      (35 +/- 6 g of CaCO3 dissolved/m3 of aquifer) and sulfide mineral oxidation (50
      +/- 10 g as FeS2/m3 after one injection). < 0.005% of the total aquifer carbonate
      matrix was dissolved during each injection event, and approximately 0.2% of the
      total reduced sulfur. Increasing amounts of ambient ground water was entrained
      into the injected mixture during each of the storage periods. High 14C(DIC)
      activities and slightly more negative delta13C(DIC) values measured immediately
      after injection events show that substantial CO2(aq) is produced by oxidation of
      organic matter associated with injectant. There were no detectable geochemical
      reactions while pumping during the recovery phase in the fifth year of the
      experiment.

PMID- 15161162
TI  - A reassessment of ground water flow conditions and specific yield at Borden and
      Cape Cod.

PMID- 15161161
TI  - Temporal changes in water quality at a childhood leukemia cluster.
AB  - Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute
      myelocytic leukemia have been diagnosed in children and teenagers who live, or
      have lived, in an area centered on the town of Fallon, Nevada. The expected rate
      for the population is about one case every five years. In 2001, 99 domestic and
      municipal wells and one industrial well were sampled in the Fallon area. Twenty
      nine of these wells had been sampled previously in 1989. Statistical comparison
      of concentrations of major ions and trace elements in those 29 wells between 1989
      and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality
      did not substantially change over that period; however, short-term changes may
      have occurred that were not detected. Volatile organic compounds were seldom
      detected in ground water samples and those that are regulated were consistently
      found at concentrations less than the maximum contaminant level (MCL). The MCL
      for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were
      commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons
      using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta
      radioactivity, arsenic, uranium, and radon concentrations in wells used by
      families having a child with leukemia did not statistically differ from the
      remainder of the domestic wells sampled during this investigation. Isotopic
      measurements indicate the uranium was natural and not the result of a 1963
      underground nuclear bomb test near Fallon. In arid and semiarid areas where trace
      element concentrations can greatly exceed the MCL, household reverse-osmosis
      units may not reduce their concentrations to safe levels. In parts of the world
      where radon concentrations are high, water consumed first thing in the morning
      may be appreciably more radioactive than water consumed a few minutes later after
      the pressure tank has been emptied because secular equilibrium between radon and
      its immediate daughter progeny is attained in pressure tanks overnight.

PMID- 15161163
TI  - Comparison of continuous and cyclic pumping from a well.

PMID- 15161164
TI  - Hydraulic conductivity prediction for sandy soils.
AB  - The potential for petroleum-contaminated soils to impact ground water is
      evaluated using the soil leachability model in South Carolina and Georgia. In
      this model, the Green and Ampt (1911) equation is used to estimate unsaturated
      flow with saturated hydraulic conductivity (K(S)) values obtained using the Rawls
      and Brakensiek (1989) equation from inputs of percent sand- and clay-sized
      particles. However, many soils have > 70% sand-sized particles, which is the
      maximum amount for which the Rawls and Brakensiek equation is valid. Therefore,
      70 sets of K(S) and particle-size data from the literature for southeastern
      United States sandy soils were analyzed to develop a new equation for estimating
      K(S). A multiple linear regression model with an adjusted R2 = 0.65 (p < 0.0001)
      was developed from percent clay- and sand-sized particle data. Eight additional
      sets of data were used to validate the model. The root mean square deviation and
      maximum squared difference, (yi - yi(2)), values for the new model are smaller
      than those obtained using the Rawls and Brakensiek equation, or Rosetta, a neural
      network-based model (Schaap 1999). The new model provides estimates that are
      within an order of magnitude for all but one of the test data sets. Rosetta
      predicts K(S) within one order of magnitude of measured values for six test data,
      and predicts K(S) within two orders of magnitude for the other two. The Rawls and
      Brakensiek predictions are within one order of magnitude for four test data, but
      are two or more orders of magnitude too high for the remaining four points. The
      new equation is recommended for estimating K(S) for sandy southeastern United
      States soils for which inputs are limited to percent sand and clay.

PMID- 15161165
TI  - Walter Curran Mendenhall: Quaker scientist.

PMID- 15161167
TI  - Use of the Ilizarov method to correct lower limb deformities in children and
      adolescents.
AB  - The introduction to the West in the early 1980s of the Ilizarov circular external
      fixator and method resulted in rapid advances in limb lengthening, deformity
      correction, and segmental long-bone defect reconstruction. The mechanical
      features of and biologic response to using distraction osteogenesis with the
      circular external fixator are the unique aspects of Ilizarov's contribution. The
      most common indications for children and adolescents are limb lengthening and
      angular deformity correction. Surgical application and postoperative management
      of the device require diligent attention to detail by both patient and surgeon.
      Also required of the surgeon is a thorough appreciation of the basic principles
      of the apparatus, mechanical axial realignment, potential complications, and
      biologic response to stretching.

PMID- 15161166
TI  - Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue
      healing.
AB  - Nonsteroidal anti-inflammatory drugs continue to be prescribed as analgesics for
      patients with healing fractures even though these drugs diminish bone formation,
      healing, and remodeling. Inhibition of bone formation can be clinically useful in
      preventing heterotopic ossification in selected clinical situations. In this
      regard, naproxen may be more efficacious than the traditional indomethacin, and
      short-term administration is as effective as long-term. When fracture healing or
      spine fusion is desired, nonsteroidal anti-inflammatory drugs should be avoided.
      Some nonsteroidal anti-inflammatory drugs have a positive effect on soft-tissue
      healing; they stimulate collagen synthesis and can increase strength in the early
      phases of repair during skin and ligament healing. Cyclooxygenase-2 inhibitors
      have an adverse effect on bone healing and may have an adverse effect on ligament
      healing. Therefore, further investigation is necessary to confirm that
      traditional nonsteroidal anti-inflammatory drugs may be preferable for the
      healing of collagenous tissues.

PMID- 15161168
TI  - Spinal epidural abscess in adults.
AB  - Spinal epidural abscess is a potentially life-threatening disease that can cause
      paralysis by the accumulation of purulent material in the epidural space.
      Although modern diagnostic and management methods have improved the prognosis,
      morbidity and mortality remain significant. Outcome usually is determined by the
      rapidity of the diagnosis and initiation of appropriate treatment. A high index
      of suspicion is warranted when a patient presents with spinal pain or a
      neurologic deficit in conjunction with fever or an elevated erythrocyte
      sedimentation rate. Gadolinium-enhanced magnetic resonance imaging should be done
      in suspected cases to localize and define the abscess. For spinal epidural
      abscess associated with neurologic compromise, the treatment of choice is
      emergent surgical decompression and debridement (with or without spinal
      stabilization), followed by long-term antimicrobial therapy. In the absence of a
      neurologic deficit, medical management is an alternative to surgery when the risk
      of neurologic complications is low based on the location and morphology of the
      abscess, immune status of the patient, and virulence of the organism.

PMID- 15161169
TI  - Stiffness after total knee arthroplasty.
AB  - Postoperative stiffness is a debilitating complication of total knee
      arthroplasty. Preoperative risk factors include limited range of motion,
      underlying diagnosis, and history of prior surgery. Intraoperative factors
      include improper flexion-extension gap balancing, oversizing or malpositioning of
      components, inadequate femoral or tibial resection, excessive joint line
      elevation, creation of an anterior tibial slope, and inadequate resection of
      posterior osteophytes. Postoperative factors include poor patient motivation,
      arthrofibrosis, infection, complex regional pain syndrome, and heterotopic
      ossification. The first steps in treating stiffness are mobilizing the patient
      and instituting physical therapy. If these interventions fail, options include
      manipulation, lysis of adhesions, and revision arthroplasty. Closed manipulation
      is most successful within the first 3 months after total knee arthroplasty.
      Arthroscopic or modified open lysis of adhesions can be considered after 3
      months. Revision arthroplasty is preferred for stiffness from malpositioned or
      oversized components. Patients who initially achieve adequate range of motion
      (>90 degrees of flexion) but subsequently develop stiffness more than 3 months
      after surgery should be assessed for intrinsic as well as extrinsic causes.

PMID- 15161170
TI  - Displaced intra-articular calcaneal fractures.
AB  - Deciding how to manage displaced intra-articular calcaneal fractures is
      challenging. Preoperative assessment of the fracture, patient status, and the
      patient's functional needs are important in determining treatment approach. In
      general, older, sedentary patients and those with no or with minimally displaced
      fractures may be treated successfully with nonsurgical management. Traits
      strongly predictive of satisfaction with surgery include age younger than 40
      years, simple fracture pattern, and accurate reduction. Smoking, diabetes, and
      peripheral vascular disease markedly increase the risk of surgical complications.
      In addition, the quality of surgical reduction affects outcome.

PMID- 15161171
TI  - Unstable intertrochanteric hip fractures in the elderly.
AB  - Unstable intertrochanteric hip fractures account for approximately one quarter of
      all hip fractures in the elderly and are increasing in frequency. Treatment goals
      include immediate mobilization while limiting complications. Preoperatively,
      medical comorbidities should be identified and managed. For stable
      intertrochanteric hip fractures, consistently good results have been achieved
      with compression hip screw fixation. However, with more unstable fracture
      patterns, problems with compression hip screw fixation, such as excessive
      fracture collapse and implant cutout, increase. For these fractures, adding a
      trochanteric stabilizing plate or using an axial compression hip screw or
      intramedullary hip screw is warranted. Surgical care should maximize the
      patient's chance of a successful outcome by realigning the fracture with minimal
      additional surgical insult, selecting the appropriate implant, and positioning it
      properly.

PMID- 15161172
TI  - On-the-field management of athletic head injuries.
AB  - Head injuries are prevalent in collision sports. Concussions represent the
      relatively benign end of the spectrum of injuries. Severe closed head injuries
      include epidural hematomas, acute subdural hematomas, intracerebral hematomas,
      intraventricular hematomas, subarachnoid hemorrhages, and diffuse axonal
      injuries. Second impact syndrome represents a severe cerebral autoregulatory
      dysfunction that can lead to death in an athlete who sustains a second (often
      minor) closed head trauma while still symptomatic from a previous head injury.
      Generally, athletes who have suffered a severe closed head injury should not
      return to play. Exceptions include athletes asymptomatic for 1 year who return to
      a noncontact sport and those who recover completely from an epidural hematoma
      without underlying brain injury. Several guidelines for returning athletes to
      play have been proposed and are commonly used. The team physician has the
      responsibility of on-the-field evaluation and management of athletes with head
      injuries, as well as of advising them when it is safe to return to play.

PMID- 15161173
TI  - Surgical management of the lower extremity in ambulatory children with cerebral
      palsy.
AB  - Despite the increasing popularity of nonorthopaedic treatment alternatives for
      children with cerebral palsy, bony and soft-tissue surgery remains a common
      component in the management of ambulatory patients. Multisite simultaneous tendon
      surgery provides improvement in gait by addressing hip, knee, and ankle
      contractures together. Careful preoperative physical examination is required;
      computerized gait analysis can be useful in confirming a plan for multiple tendon
      surgeries. Rotational osteotomies can improve transverse-plane malalignment.
      Shorter periods of immobilization and aggressive postoperative gait training and
      strengthening may optimize improvements in gait.

PMID- 15161174
TI  - Biomedical applications of poisonous plant research.
AB  - Research designed to isolate and identify the bioactive compounds responsible for
      the toxicity of plants to livestock that graze them has been extremely
      successful. The knowledge gained has been used to design management techniques to
      prevent economic losses, predict potential outbreaks of poisoning, and treat
      affected animals. The availability of these compounds in pure form has now
      provided scientists with tools to develop animal models for human diseases, study
      modes of action at the molecular level, and apply such knowledge to the
      development of potential drug candidates for the treatment of a number of genetic
      and infectious conditions. These advances are illustrated by specific examples of
      biomedical applications of the toxins of Veratrum californicum (western false
      hellebore), Lupinus species (lupines), and Astragalus and Oxytropis species
      (locoweeds).

PMID- 15161175
TI  - Development of a fluorescent latex immunoassay for detection of a spectinomycin
      antibiotic.
AB  - There is a need to develop a rapid and sensitive method to detect spectinomycin
      residues in animal tissues. A latex fluorescent immunoassay was designed using
      reagents developed for this assay. The spectinomycin antibody was produced in
      sheep, and the immunoglobulin (IgG) was purified through a Protein G affinity
      column and was immobilized onto latex particles. Spectinomycin was labeled with 5
      ([4,6-dichlorotriazin-2-yl]amino)fluorescein (DTAF). The optimum assay conditions
      consisted of preincubating the latex-IgG with spectinomycin in buffer solutions
      or in bovine kidney extracts. DTAF-spectinomycin was added and was further
      incubated. The bound spectinomycin-DTAF/IgG-latex complex was separated by
      centrifugation at 4000 g for 10 min. The fluorescence signals of the unbound
      spectinomycin-DTAF in the supernatant were measured at 485/535 nm
      excitation/emission. The measured signals were directly proportional to the
      concentration of spectinomycin in the samples, and spectinomycin was detected at
      0-100 ppb with minimum detectability of 5 ppb. The mean regression correlation of
      four trials in buffer was 0.936 when the % bound complex vs spectinomycin
      concentration was plotted. Analysis of the kidney extract spiked with 0-100 ppb
      spectinomycin had a regression correlation of 0.959. This assay provides a rapid
      screening method for low ppb detection of spectinomycin.

PMID- 15161176
TI  - Quantification of saccharides in multiple floral honeys using fourier transform
      infrared microattenuated total reflectance spectroscopy.
AB  - Fourier transform infrared (FTIR) spectroscopy with microattenuated total
      reflectance (mATR) sampling accessory and chemometrics (partial least squares and
      principal component regression) was used for the simultaneous determination of
      saccharides such as fructose, glucose, sucrose, and maltose in honey. Two
      calibration models were developed. The first model used a set of 42 standard
      mixtures of fructose, glucose, sucrose, and maltose prepared over the range of
      concentrations normally present in honey, whereas the second model used a set of
      45 honey samples from various floral and regional sources. The developed models
      were validated with different data sets and verified by high-performance liquid
      chromatography (HPLC) measurements. The R (2) values between the FTIR-mATR
      predicted and HPLC results of the different sugars were between 0.971 and 0.993,
      demonstrating the predictive ability and accuracy of the procedure.

PMID- 15161178
TI  - Direct optical biosensor analysis of folate-binding protein in milk.
AB  - An automated, rapid, sensitive, and label-free biosensor-based assay for folate
      binding protein (FBP) in bovine milk utilizing surface plasmon resonance optical
      detection is described. The active concentration of FBP is estimated from its
      specific interaction with a pteroyl-l-glutamic (folic) acid derivative
      immobilized on the sensor surface in a direct binding assay format. Milk,
      colostrum, and milk powders are prepared for analysis by dilution into buffer.
      Analysis conditions, including ligand immobilization, flow rate, contact time,
      and regeneration, have been defined, and nonspecific binding considerations were
      evaluated. Performance parameters include a working range for FBP in buffer of 0
      200 ng/mL, a method detection limit of 0.13 microg/mL in fluid milk, overall
      instrument response RSD(R) of 0.64%, a mean interassay RSD(R) of 7.3% for skim
      milk powder, and surface stability over ca. 200 samples. The technique was
      applied to the measurement of active FBP content of consumer milks, the heat
      classification of skim milk powders manufactured under a wide range of thermal
      processing protocols, and change during early bovine lactation.

PMID- 15161177
TI  - The effects of sample preparation and gas chromatograph injection techniques on
      the accuracy of measuring guaiacol, 4-methylguaiacol and other volatile oak
      compounds in oak extracts by stable isotope dilution analyses.
AB  - The deuterium-labeled standards [(2)H(3)]-guaiacol and [(2)H(3)]-4-methylguaiacol
      were synthesized and utilized in a method employing gas chromatography-mass
      spectrometry to determine the concentration of guaiacol and 4-methylguaiacol in
      wine or extracts of oak shavings. The method was combined with previously
      published methods for 4-ethylphenol, 4-ethylguaiacol, cis- and trans-oak lactone
      and vanillin, so that all these compounds could be quantified in a single
      analysis. The method can employ either liquid-liquid extraction or headspace
      solid-phase microextraction (SPME) and is rapid, robust, precise, and accurate.
      Under certain conditions, there was artifactual generation, to varying degrees,
      of guaiacol, 4-methylguaiacol, cis-oak lactone, and vanillin during the analysis
      of oak extracts, especially when diethyl ether extraction and injector block
      temperatures at or above 225 degrees C were employed. The most substantial
      effects were observed for guaiacol, in which results could be exaggerated by over
      10 times. These artifacts could be avoided by using headspace SPME or by
      preparing liquid-liquid extracts with pentane or pentane/diethyl ether (2:1)
      injected at 200 degrees C providing spot checks using headspace SPME were
      performed. Data obtained for previously published quantitative determination of
      guaiacol in oak extracts should be reexamined carefully, with special attention
      paid to their respective methods of sample preparation and analysis.

PMID- 15161179
TI  - Determination of caffeine, theobromine, and theophylline in standard reference
      material 2384, baking chocolate, using reversed-phase liquid chromatography.
AB  - A rapid and selective isocratic reversed-phase liquid chromatographic method has
      been developed at the National Institute of Standards and Technology to
      simultaneously measure caffeine, theobromine, and theophylline in a food-matrix
      standard reference material (SRM) 2384, Baking Chocolate. The method uses
      isocratic elution with a mobile phase composition (volume fractions) of 10%
      acetronitrile/90% water (pH adjusted to 2.5 using acetic acid) at a flow rate of
      1.5 mL/min with ultraviolet absorbance detection (274 nm). Total elution time for
      these analytes is less than 15 min. Concentration levels of caffeine,
      theobromine, and theophylline were measured in single 1-g samples taken from each
      of eight bars of chocolate over an eight-day period. Samples were defatted with
      hexane, and beta-hydroxyethyltheophylline was added as the internal standard. The
      repeatability for the caffeine, theobromine, and theophylline measurements was
      5.1, 2.3, and 1.9%, respectively. The limit of quantitation for all analytes was
      <100 ng/mL. The measurements from this method were used in the value-assignment
      of caffeine, theobromine, and theophylline in SRM 2384.

PMID- 15161180
TI  - Detection of genetically modified maize MON810 and NK603 by multiplex and real
      time polymerase chain reaction methods.
AB  - In this study, the event-specific primers for insecticide-resistant maize,
      MON810, and herbicide-tolerance maize, NK603, have been designed. Simplex PCR and
      multiplex PCR detection method have been developed. The detection limit of the
      multiplex PCR is 0.5% for MON810 and NK603 in 50 ng of the template for one
      reaction. Quantitative methods based on real-time quantitative PCR were developed
      for MON810 and NK603. Plasmid pMulM2 as reference molecules for the detection of
      MON810 and NK603 was constructed. Quantification range was from 0.5 to 100% in
      100 ng of the DNA template for one reaction. The precision of real-time Q-PCR
      detection methods, expressed as coefficient of variation for MON810 and NK603
      varied from 1.97 to 8.01% and from 3.45 to 10.94%, respectively. The range agreed
      with European interlaboratories test results (25%). According to the results, the
      methods for quantitative detection of genetically modified maize were acceptable.

PMID- 15161181
TI  - Qualitative and quantitative PCR methods for detection of three lines of
      genetically modified potatoes.
AB  - Qualitative and quantitative polymerase chain reaction (PCR) methods have been
      developed for the detection of genetically modified (GM) potatoes. The
      combination of specific primers for amplification of the promoter region of Cry3A
      gene, potato leafroll virus replicase gene, and potato virus Y coat protein gene
      allows to identify each line of NewLeaf, NewLeaf Y, and NewLeaf Plus GM potatoes.
      Multiplex PCR method was also established for the simple and rapid detection of
      the three lines of GM potato in a mixture sample. For further quantitative
      detection, the realtime PCR method has been developed. This method features the
      use of a standard plasmid as a reference molecule. Standard plasmid contains both
      a specific region of the transgene Cry3A and an endogenous UDP-glucose
      pyrophosphorylase gene of the potato. The test samples containing 0.5, 1, 3, and
      5% GM potatoes were quantified by this method. At the 3.0% level of each line of
      GM potato, the relative standard deviations ranged from 6.0 to 19.6%. This result
      shows that the above PCR methods are applicable to detect GM potatoes
      quantitatively as well as qualitatively.

PMID- 15161182
TI  - Development of a seven-target multiplex PCR for the simultaneous detection of
      transgenic soybean and maize in feeds and foods.
AB  - The detection of genetically modified organisms (GMOs) in food and feed is an
      important issue for all the subjects involved in raw material control, food
      industry, and distribution. Because the number of GMOs authorized in the EU
      increased during the past few years, there is a need for methods that allow a
      rapid screening of products. In this paper, we propose a method for the
      simultaneous detection of four transgenic maize (MON810, Bt11, Bt 176, and GA21)
      and one transgenic soybean (Roundup Ready), which allows routine control analyses
      to be sped up. DNA was extracted either from maize and soybean seeds and leaves
      or reference materials, and the recombinant DNA target sequences were detected
      with 7 primer pairs, accurately designed to be highly specific for each
      investigated transgene. Cross and negative controls were performed to ensure the
      specificity of each primer pair. The method was validated on an interlaboratory
      ring test and good analytical parameters were obtained (LOD = 0.25%,
      Repeatability, (r) = 1; Reproducibility, (R) = 0.9). The method was then applied
      to a model biscuit made of transgenic materials baked for the purpose and to real
      samples such as feed and foodstuffs. On account of the high recognition
      specificity and the good detection limits, this multiplex PCR represents a fast
      and reliable screening method directly applicable in all the laboratories
      involved in raw material and food control.

PMID- 15161183
TI  - Resonance Raman quantification of nutritionally important carotenoids in fruits,
      vegetables, and their juices in comparison to high-pressure liquid chromatography
      analysis.
AB  - A rapid nondestructive estimation of carotenoid levels in intact fruits and
      vegetables and their juices could have great value when selecting nutritionally
      valuable crops for further propagation and commercial use. Carotenoid levels of a
      variety of agricultural products and juices were measured using resonance Raman
      spectroscopy and compared to levels determined by extraction and high-pressure
      liquid chromatography. A strong correlation was observed between the two methods
      when evaluating juices and when comparing different strains of intact tomatoes at
      the same stage of ripening.

PMID- 15161184
TI  - Simple and rapid liquid chromatography-tandem mass spectrometry confirmatory
      assay for determining amoxicillin and ampicillin in bovine tissues and milk.
AB  - A simple specific and rapid confirmatory method for determining the two
      amphoteric penicillins, that is, amoxicillin and ampicillin, in bovine muscle,
      liver, kidney, and milk is presented. This method is based on the matrix solid
      phase dispersion technique with hot water as extractant followed by liquid
      chromatography (LC)-tandem mass spectrometry. With this instrumentation, the
      selected reaction monitoring acquisition mode with two fragmentation reactions
      for each analyte was adopted. After acidification and filtration of the aqueous
      extracts, 25 microL of the tissue final extracts and 50 microL of the milk final
      extract were injected into the LC apparatus. Absolute recovery of the two
      analytes in any biological matrix at the 50 ppb level in tissues and the 4 ppb
      level in milk was 74-95% with relative standard deviations (RSDs) of no larger
      than 9%. When penicillin V was used as surrogate internal standard, relative
      recovery of the targeted compounds present in bovine tissues and milk at,
      respectively, 25 and 2 ppb levels ranged between 100 and 106% with RSDs of no
      larger than 11%. When fractionation of analytes by using a short chromatographic
      run was attempted, remarkable signal weakening for the two analytes was
      experienced. This effect was traced to polar endogenous coextractives eluted in
      the first part of the chromatographic run that interfered with the gas-phase ion
      formation of the two penicillins. Slowing the chromatographic run eliminated this
      unwelcome effect. Limits of quantification of the two analytes in bovine milk
      were estimated to be <1 ppb, whereas amoxicillin and ampicillin could be
      quantified in bovine tissues down to 3.1 and 0.8 ppb levels, respectively.

PMID- 15161185
TI  - Chemical constituents, antifungal and antioxidative effects of ajwain essential
      oil and its acetone extract.
AB  - GC and GC-MS analysis of ajwain essential oil showed the presence of 26
      identified components which account for 96.3% of the total amount. Thymol (39.1%)
      was found as a major component along with p-cymene (30.8%), gamma-terpinene
      (23.2%), beta-pinene (1.7%), terpinene-4-ol (0.8%) whereas acetone extract of
      ajwain showed the presence of 18 identified components which account for 68.8% of
      the total amount. The major component was thymol (39.1%) followed by oleic acid
      (10.4%), linoleic acid (9.6%), gamma-terpinene (2.6%), p-cymene (1.6%), palmitic
      acid (1.6%), and xylene (0.1%). Moreover, the oil exhibited a broad spectrum of
      fungitoxic behavior against all tested fungi such as Aspergillus niger,
      Aspergillus flavus, Aspergillus oryzae, Aspergillus ochraceus, Fusarium
      monoliforme, Fusarium graminearum, Pencillium citrium, Penicillium viridicatum,
      Pencillium madriti, and Curvularia lunata as absolute mycelial zone inhibition
      was obtained at a 6-microL dose of the oil. However, the acetone extract showed
      better antioxidative activity for linseed oil as compared with synthetic
      antioxidants such as butylated hydroxyl toluene and butylated hydroxyl anisole.

PMID- 15161186
TI  - Antifungal chalcones and new caffeic acid esters from Zuccagnia punctata acting
      against soybean infecting fungi.
AB  - The crude methanolic extract of Zuccagnia punctata was active toward the fungal
      pathogens of soybean Phomopsis longicolla and Colletotrichum truncatum. Assay
      guided fractionation led to the isolation of two chalcones, one flavanone and a
      new caffeoyl ester derivative as the compounds responsible for the antifungal
      activity. Another new caffeoyl ester derivative was isolated from the antifungal
      chloroform extract but proved to be inactive against the soybean infecting fungi
      up to 50 microg/mL

PMID- 15161187
TI  - Grape seed extract affects proliferation and differentiation of human intestinal
      Caco-2 cells.
AB  - The effect of daily contact of a grape seed extract (GSE) on Caco-2 cell
      proliferation and differentiation was investigated. GSE at 400 mg/L was added to
      Caco-2 cells for 2 h a day after successive incubation in saliva, gastric, and
      pancreatic media. When applied at the beginning of the cell culture, GSE
      triggered inhibition of cell growth associated with a possible cytotoxic
      reaction. On the other hand, when the treatment was applied to confluent cells,
      treated cells displayed a higher protein content than control cells and a more
      developed brush border, with taller and denser microvilli. These observations
      were accompanied by stimulation of alkaline phosphatase activity, especially at
      day 5 postconfluency, with a 2.2-fold increase in comparison with the control. On
      the other hand, aminopeptidase N activity was inhibited throughout the
      differentiation period in GSE-treated cells to reach 28.8% of control cell
      activity on day 30. GSE did not affect either sucrase-isomaltase activity or
      cytoplasmic lactate dehydrogenase (LDH) activity, which otherwise appeared to be
      a good cellular marker. GSE treatment of Caco-2 cells thus inhibited their
      proliferation from seeding onward and stimulated both proliferation and
      differentiation after confluency.

PMID- 15161188
TI  - In vitro antioxidant, antimicrobial, and antiviral activities of the essential
      oil and various extracts from herbal parts and callus cultures of Origanum
      acutidens.
AB  - The essential oil and various extracts obtained from Origanum acutidens and
      methanol extracts (MeOH) from callus cultures have been evaluated for their
      antioxidative, antimicrobial, and antiviral properties. The essential oil
      exhibited strong antimicrobial activity with a significant inhibitory effect
      against 27 (77%) of the 35 bacteria, 12 (67%) of the 18 fungi, and a yeast tested
      and moderate antioxidative capacity in DPPH and beta-carotene/linoleic acid
      assays. GC and GC-MS analyses of the oil resulted in the identification of 38
      constituents, carvacrol being the main component. The MeOH extracts obtained from
      herbal parts showed better antioxidative effect than that of butylated
      hydroxytoluene (BHT), whereas callus cultures also exhibited interesting
      antioxidative patterns. Concerning antiviral activity, none of the extracts
      inhibited the reproduction of influenza A/Aichi virus in MDCK cells. The MeOH
      extracts from herbal parts inhibited the reproduction of HSV-1, and also callus
      cultures exerted slight antiherpetic effect.

PMID- 15161189
TI  - 1,3-beta-glucan quantification by a fluorescence microassay and analysis of its
      distribution in foods.
AB  - The objective of this study was to establish analytical approaches to quantify
      1,3-beta-glucan (1,3-beta-G) in foods. Six food categories including legumes,
      cereals, tubers, vegetables, fruits, and mushrooms and 17 total items were
      tested. An extraction procedure was designed to prepare food cold-water soluble,
      hot-water soluble, cold-alkaline soluble, and hot-alkaline soluble fractions. A
      fluorescence microassay based on aniline blue dye, which bound specifically to
      1,3-beta-G, was developed to measure its content in the food fractions. Curdlan
      was used as standard to construct the 1,3-beta-G calibration curve, and a linear
      correlation within a 14 microg/mL concentration range was obtained. This
      microassay displayed selectivities among various 1,3-beta-G species. Biologically
      active ones such as pachyman and yeast glucan possessed much stronger fluorescent
      signals than others such as laminarin and barley glucan. Possible fluorescent
      interference from food proteins was estimated. This assay tolerated up to 50% of
      bovine serum albumin in 10 microg/mL curdlan. Analysis of the four food fractions
      showed that besides the well-known lentinan-containing shiitake, popular foods
      such as celery, chin-chian leaves, carrot, and radish contained nearly 20% 1,3
      beta-G in their total sugar. Soybean dry weight contained 0.8% 1,3-beta-G, which
      was twice the amount compared to shiitake. Snow mushroom dry weight had the
      highest 1,3-beta-G content, at 2.5%, and was rich in both water (0.67%) and
      alkaline soluble (1.87%) forms. In conclusion, this dye-binding fluorescence
      microassay in conjunction with the extraction procedure can be applied in the
      prescreening of potential foods rich in functional 1,3-beta-G.

PMID- 15161190
TI  - Quantitative analysis of anti-inflammatory and radical scavenging triterpenoid
      esters in evening primrose oil.
AB  - Cold pressed, nonraffinated evening primrose oil (EPO) was recently found to
      contain lipophilic triterpenoidal esters with radical scavenging and anti
      inflammatory properties. A simple and robust method for the quantitative analysis
      of these 3-O-trans-caffeoyl derivatives of betulinic, morolic, and oleanolic acid
      was developed and validated. Separation was achieved by normal phase
      chromatography on a Diol column and with hexane/ethyl acetate (50:50) as eluent.
      The analytes could be determined directly in the oil matrix, without need of a
      previous removal of the triglycerides. Normal phase LC ESI-MS with a makeup flow
      of polar modifier was used for checking the identity and purity of analyte peaks.
      Samples from 22 commercially available EPOs were analyzed. The average caffeoyl
      ester contents were 58 mg/100 g in cold pressed oils and 4.7 mg/100 g in
      partially raffinated oils. In fully raffinated EPO samples, the concentration was
      below the limit of detection. The influence of extraction temperature on the
      content of caffeoyl esters in nonraffinated EPO was investigated with seeds of
      Oenothera biennis and Oenothera lamarckiana, respectively. With O. lamarckiana,
      the concentration of caffeoyl esters in the oil increased with rising pressure
      and temperature, whereas no such dependency was found with O. biennis.
      Microscopic analysis revealed some differences in the histology of the seed
      testa, which may explain in part the differing behaviors in the extraction
      experiments. There was a difference between O. biennis and O. lamarckiana oils
      with respect to the relative amounts of the three esters. The temperature of the
      extraction process had no effect on the ratio of the compounds.

PMID- 15161191
TI  - Insect antifeedants from tropical plants: structures of dumnin and dumsenin.
AB  - Two novel A-seco limonoids, dumnin and dumsenin, were isolated from the
      methanolic extract of Croton jatrophoides by bioassay-guided fractionation, and
      the structures were determined by nuclear magnetic resonance, circular dichroism,
      and mass spectrometry experiments. These compounds showed potent antifeedant
      activity (PC(50) <or= 2.0 microg/mL) against the larvae of pink bollworm,
      Pectinophora gossypiella, and/or fall armyworm, Spodoptera frugiperda, providing
      results comparable to dumsin and zumsin, previously isolated from the same plant.

PMID- 15161192
TI  - Antibacterial activity of coriander volatile compounds against Salmonella
      choleraesuis.
AB  - Aliphatic (2E)-alkenals and alkanals characterized from the fresh leaves of the
      coriander Coriandrum sativum L. (Umbelliferae) were found to possess bactericidal
      activity against Salmonella choleraesuis ssp. choleraesuis ATCC 35640. (2E)
      Dodecenal (C(12)) was the most effective against this food-borne bacterium with
      the minimum bactericidal concentration (MBC) of 6.25 microg/mL (34 microM),
      followed by (2E)-undecenal (C(11)) with an MBC of 12.5 microg/mL (74 microM). The
      time-kill curve study showed that these alpha,beta-unsaturated aldehydes are
      bactericidal against S. choleraesuis at any growth stage and that their
      bactericidal action comes in part from the ability to act as nonionic
      surfactants.

PMID- 15161193
TI  - Quantification of uronic acids in tea polysaccharide conjugates and their
      antioxidant properties.
AB  - A technique of high-performance liquid chromatography (HPLC) was described for
      the measurement of total uronic acids in tea polysaccharide conjugates. This
      method was applied to polysaccharide conjugate extracts obtained from green tea
      after most of the components that produce interference were removed. The
      preliminary extraction process was according to the procedure of isolation of
      polysaccharide conjugates. The uronic acid content of different polysaccharide
      conjugate fractions was quantified by HPLC on a Sugar-Pak I column with a 1.0 x
      10(-)(4) mol x L(-)(1) calcium disodium ethylenediaminetetraacetic acid solution
      as the mobile phase and refractive index detection. The validation study showed
      high recoveries (>97.0%) and low coefficients of variance (<3.0%). The minimum
      detectable limit concentration of uronic acid was 10 microg x mL(-)(1). The
      analysis of a standard range of galacturonic acid concentrations (100-4000 microg
      x mL(-)(1)) yielded linear results. The use of the method on different
      polysaccharide conjugate fraction samples confirmed its effectiveness. With the
      high content of uronic acids in polysaccharide conjugates, the stronger reactive
      oxygen species scavenging activities were found.

PMID- 15161194
TI  - Herbicidal pyridyl derivatives of aminomethylene-bisphosphonic acid inhibit plant
      glutamine synthetase.
AB  - A series of aminomethylene-bisphosphonic acid derivatives, previously synthesized
      and shown to be endowed with herbicidal properties, were evaluated as potential
      inhibitors of plant glutamine synthetase. The cytosolic form of the enzyme was
      partially purified from rice cultured cells and assayed in the presence of
      millimolar concentrations of the compounds by means of three different assay
      methods, respectively measuring the hemibiosynthetic, the transferase, and the
      full biosynthetic reactions. Several compounds were found to exert a remarkable
      inhibition, with I(50) values similar to those obtained under the same conditions
      with a well-established inhibitor of glutamine synthetase, the herbicide
      phosphinothricin. Contrary to the reference compound, enzyme kinetics accounted
      for a reversible inhibition mechanism. The biological activity of the most active
      derivatives was further characterized by measuring free glutamine levels in cell
      suspension rice cultures following treatment with the inhibitors. Results
      confirmed their ability to interfere in vivo with nitrogen metabolism. A
      preliminary analysis of structure-activity relationship allowed it to be
      hypothesized that steric rather than electronic factors are responsible for the
      inhibitory potential of these compounds.

PMID- 15161195
TI  - Phytotoxins from the leaves of Ruta graveolens.
AB  - Bioassay-guided fractionation of the ethyl acetate extract of Ruta graveolens
      (common rue) leaves led to the isolation of the furanocoumarins 5-methoxypsoralen
      (5-MOP), 8-methoxypsoralen (8-MOP), and the quinolone alkaloid graveoline as
      phytotoxic constituents. Graveoline and 8-MOP substantially inhibited growth of
      Lactuca sativa (lettuce) seedlings and reduced chlorophyll content at 100 microM;
      this effect was not due to a direct effect on chlorophyll synthesis. Radical
      growth of L. sativa was inhibited by 10 microM 8-MOP. Graveoline inhibited growth
      of Lemna paucicostata (duckweed) at 100 microM. This is the first report of the
      phytotoxic activity of graveoline. Growth of Agrostis stolonifera (bentgrass) was
      inhibited by 5-MOP at 30 microM. All three compounds substantially reduced cell
      division in Allium cepa (onion) at or below 100 microM. None of the compounds
      caused significant cellular leakage of Cucumis sativus (cucumber) cotyledon disks
      at 100 microM. All three compounds inhibit plant growth, at least partially
      through inhibition of cell division.

PMID- 15161196
TI  - The 26S proteasome in garlic (Allium sativum): purification and partial
      characterization.
AB  - The 26S proteasome (multicatalytic protease complex, MPC) was purified from fresh
      garlic cloves (Allium sativum) to near homogeneity by ion exchange chromatography
      on DEAE-sephacel, gel filtration on Sepharose-4B, and glycerol density gradient
      centrifugation. Two alpha-type (20S proteasome "catalytic core") subunits were
      identified by the direct sequencing of peptide fragments (mass fingerprint
      analysis, Mass Spectrometry Lab, Stanford University) or the sequencing of a
      cloned cDNA generated using a garlic cDNA library as the template; these subunits
      were found to have a high homology to those from other plants. Polyacrylamide gel
      electrophoresis under denaturing conditions separated the garlic MPC into
      multiple polypeptides having molecular masses in the range of 21-35 (components
      of the 20S catalytic core) and 55-100 kDa (components of the 19S regulatory
      units). The banding pattern of the garlic MCP is similar to that of spinach and
      rat liver with minor differences in some components; however, polyclonal
      antibodies against mammalian proteasomes failed to significantly stain the enzyme
      from garlic. This is the first work to identify the garlic proteasome.

PMID- 15161197
TI  - Studies on cultivation kinetics for elastase production by Bacillus sp. EL31410.
AB  - It was the first time to study elastase batch cultivation kinetics. This paper
      discusses the growth kinetics, elastase production, and substrate consumption
      kinetics model of Bacillus sp. EL31410 in batch cultivation. A simple model was
      proposed using a logistic equation for growth, the Luedeking-Piret equation for
      elastase production, and the Luedeking-Piret-like equation for glucose
      consumption. The model appeared to provide a reasonable description for each
      parameter during the growth phase. This study could provide some support for
      studying elastase fermentation kinetics, especially for studying its singular
      growth phenomenon. However, the model for elastase production is not good for
      explaining the real process and is still up to research.

PMID- 15161198
TI  - Production of polyclonal antibodies against territrem B and detection of
      territrem B in the conidia of Aspergillus terreus 23-1 by immunoelectron
      microscopy.
AB  - Territrem B, a fungal metabolite isolated from Aspergillums terreus 23-1, is a
      tremorgenic mycotoxin. Immunoelectron microscopy using anti-territrem B
      polyclonal antibody was used to detect territrem B in the fungal body of A.
      terreus 23-1 at different times of culture without shaking on potato dextrose
      (PD) agar medium. The anti-territrem B serum was produced by immunization of
      rabbits with 4beta-hydroxymethyl-4beta-demethylterritrem B-sccinate bound by a
      linker to keyhole limpet hemocyanin. This antiserum recognized territrems and
      immunoelectron microscopy using this antiserum, and colloidal gold-conjugated
      anti-rabbit IgG antibodies showed that territrem B was localized to the fungal
      body of A. terreus 23-1. Territrem B was first seen in the cytoplasm of the
      conidia after 4 days' culture on PD agar medium. Maximal territrem B production
      in the conidia was seen on the 14th day of culture; however, territrem B was not
      formed in the hyphae at any stage of culture. These results are consistent with
      the previous finding that the formation of territrems is related to fungal
      sporulation.

PMID- 15161199
TI  - DNA fingerprinting and quality traits of Corbarino cherry-like tomato landraces.
AB  - Twenty-five landraces of the cherry-like tomato named Corbarino, a typical niche
      product grown in the Sarno valley of the Campania region, have been
      characterized. The landraces used have been compared to eight cultivars widely
      spread in the same area of cultivation. The genetic diversity within and between
      landraces was evaluated through the comparison of DNA fingerprints obtained with
      (GATA)(4) probe hybridized to TaqI digested genomic DNA. Twenty-two of the
      Corbarino landraces were homogeneous and were unequivocally characterized by
      their DNA fingerprints. The others are probably "population varieties" in that
      within each of them polymorphic DNA fragments were identified. According to the
      characterization of fruit shapes, four groups were identified. One landrace from
      each group, harvested at the same ripening degree, was further characterized for
      yield, fruit quality components, antioxidant activities, and carotenoid contents
      and compared to Faino F(1) and Tomito F(1) hybrids. The Corbarino landraces were
      all characterized by high yield, a high level of carbohydrates, and high levels
      of soluble and total solids. Interestingly, the biotype named ISCI 05 was the
      most suitable for canning. Landraces ISCI 07 and ISCI 05 gave the highest value
      of antioxidant activities and carotenoid content. These data, together with
      previously published results, suggested that ISCI 05 should be proposed for the
      institution of a Label of Origin.

PMID- 15161200
TI  - Validation of a rice specific gene, sucrose phosphate synthase, used as the
      endogenous reference gene for qualitative and real-time quantitative PCR
      detection of transgenes.
AB  - With the development of transgenic crops, many countries have issued regulations
      to label the genetically modified organisms (GMOs) and their derived products.
      Polymerase Chain Reaction (PCR) methods are thought to be reliable and useful
      techniques for qualitative and quantitative detection of GMOs. These methods
      generally need to amplify the transgene and compare the amplified result with
      that of the corresponding reference gene to obtain reliable results. In this
      article, we reported the development of specific primers and probe for the rice
      (Oryza sativa) sucrose phosphate synthase (SPS) gene and PCR cycling conditions
      suitable for the use of this sequence as an endogenous reference gene in both
      qualitative and quantitative PCR assays. Both methods were assayed with 13
      different rice varieties, and identical amplification products were obtained with
      all of them. No amplification products were observed when DNA samples from other
      species, such as wheat, maize, barley, tobacco, soybean, rapeseed, tomato,
      sunflower, carrot, pepper, eggplant, lupine, mung bean, plum, and Arabidopsis
      thaliana, were used as templates, which demonstrated that this system was
      specific for rice. In addition, the results of the Southern blot analysis
      confirmed that the SPS gene was a single copy in the tested rice varieties. In
      qualitative and quantitative PCR analyses, the detection sensitivities were 0.05
      and 0.005 ng of rice genomic DNA, respectively. To test the practical use of this
      SPS gene as an endogenous reference gene, we have also quantified the beta
      glucuronidase (GUS) gene in transgenic rice using this reference gene. These
      results indicated that the SPS gene was species specific, had one copy number,
      and had a low heterogeneity among the tested cultivars. Therefore, this gene
      could be used as an endogenous reference gene of rice and the optimized PCR
      systems could be used for practical qualitative and quantitative detection of
      transgenic rice.

PMID- 15161202
TI  - Radiation-induced enhancement of antioxidant contents of soybean (Glycine max
      Merrill).
AB  - Soybean samples were treated with gamma-radiation doses between 0.5 and 5 kGy for
      achieving insect disinfestation and microbial decontamination. Nutritional
      quality of soybeans with respect to antioxidant isoflavone content was tested in
      radiation-treated and untreated samples. Changes in major isoflavones such as
      genistein, diadzein, glycetein, and their glycosides were monitored by high
      performance liquid chromatography. Interestingly, a decrease in content of
      glycosidic conjugates and an increase in aglycons were noted with increasing
      radiation dose. Antioxidant potential measured as percent 1,1-diphenyl-2
      picrylhydrazyl scavenging activity showed an increasing trend with dose,
      indicating that radiation processing as a method of food preservation has a
      positive nutritional implication.

PMID- 15161201
TI  - Antioxidant and cellular activities of anthocyanins and their corresponding
      vitisins A--studies in platelets, monocytes, and human endothelial cells.
AB  - During red wine aging, there is a loss of anthocyanins and the formation of
      various other pigments, so-called vitisins A, which are formed through the
      chemical interaction of the original anthocyanins with pyruvic acid. The
      objective of this study was to investigate the antioxidant activities of the most
      abundant anthocyanins present in red wine (glycosides of delphinidin, petunidin,
      and malvidin) and their corresponding vitisins A. Anthocyanins exhibited a higher
      iron reducing as well as 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulfonate) and
      peroxyl radical scavenging activity than their corresponding vitisins A.
      Delphinidin showed the highest antioxidant effect of the tested compounds in all
      of the assays used. Furthermore, we studied the effect of anthocyanins and
      vitisins A on platelet aggregation and monocyte and endothelial function.
      Anthocyanins and vitisins did not affect nitric oxide production and tumor
      necrosis factor-alpha (TNF-alpha) secretion in lipopolysaccharide plus interferon
      gamma-activated macrophages. Furthermore, anthocyanins and vitisins did not
      change collagen-induced platelet aggregation in vitro. However, anthocyanins and
      to a lesser extent vitisins exhibited protective effects against TNF-alpha
      induced monocyte chemoattractant protein production in primary human endothelial
      cells.

PMID- 15161203
TI  - Effect of heat treatment on the antioxidant activity of extracts from citrus
      peels.
AB  - The effect of heat treatment on the antioxidant activity of extracts from Citrus
      unshiu peels was evaluated. Citrus peels (CP) (5 g) were placed in Pyrex Petri
      dishes (8.0 cm diameter) and heat-treated at 50, 100, or 150 degrees C for 10,
      20, 30, 40, 50, and 60 min in an electric muffle furnace. After heat treatment,
      70% ethanol extract (EE) and water extract (WE) (0.1 g/10 mL) of CP were
      prepared, and total phenol contents (TPC), radical scavenging activity (RSA), and
      reducing power of the extracts were determined. The antioxidant activities of CP
      extracts increased as heating temperature increased. For example, heat treatment
      of CP at 150 degrees C for 60 min increased the TPC, RSA, and reducing power of
      EE from 71.8 to 171.0 microM, from 29.64 to 64.25%, and from 0.45 to 0.82,
      respectively, compared to non-heat-treated control. In the case of WE from CP
      heat-treated at the same conditions (150 degrees C for 60 min), the TPC, RSA, and
      reducing power also increased from 84.4 to 204.9 microM, from 15.81 to 58.26%,
      and from 0.27 to 0.96, respectively. Several low molecular weight phenolic
      compounds such as 2,3-diacetyl-1-phenylnaphthalene, ferulic acid, p
      hydroxybenzaldoxime, 5-hydroxyvaleric acid, 2,3-diacetyl-1-phenylnaphthalene, and
      vanillic acid were newly formed in the CP heated at 150 degrees C for 30 min.
      These results indicated that the antioxidant activity of CP extracts was
      significantly affected by heating temperature and duration of treatment on CP and
      that the heating process can be used as a tool for increasing the antioxidant
      activity of CP.

PMID- 15161204
TI  - Improving xanthophyll extraction from marigold flower using cellulolytic enzymes.
AB  - In this work is studied the effect of a noncommercial enzyme preparation on
      xanthophyll extraction from marigold flower (Tagetes erecta). The enzymatic
      extract was synthesized by endogenous microorganisms previously isolated and
      identified as Flavobacterium IIb, Acinetobacter anitratus, and Rhizopus
      nigricans. The results show that the extraction yield depends directly on the
      extent of the enzymatic hydrolysis of cell walls in the flower petals and that it
      is possible to reach yields in excess of those previously reported for treatments
      with commercially available enzymes (29.3 g/kg of dry weight). HPLC analysis of
      the product indicates that the original xanthophyll profile is not altered. The
      enhanced extraction system appears to be very competitive when compared to the
      traditional process and current alternatives.

PMID- 15161205
TI  - Ascorbic acid oxidation in sucrose aqueous model systems at subzero temperatures.
AB  - The reduction of Tempol by ascorbic acid in concentrated sucrose solutions was
      measured by electron paramagnetic resonance (EPR) at temperatures ranging from 16
      to -16 degrees C. This method allowed the determination of the rate constants (k)
      of this fast reaction, by recording the Tempol reduction as a function of time.
      The two reactants were initially separated and had to migrate for the reaction to
      occur. The experimental findings were compared with predicted values according to
      the equation for diffusion-controlled reaction proposed by Atkins. The
      experimental reaction rate constants were observed to be lower than the
      calculated ones. However, the experimental values were found to be controlled by
      the temperature and viscosity changes of the reaction media, as expected for a
      diffusion-controlled reaction.

PMID- 15161206
TI  - Effect of soy milk characteristics and cooking conditions on coagulant
      requirements for making filled tofu.
AB  - The amount of coagulant added to soy milk is a critical factor for tofu-making;
      particularly it affects the textural properties of tofu. Earlier research
      indicated that the critical point of coagulant concentration (CPCC) is a
      characteristic parameter of soy milk and could be used as an effective indicator
      of optimal coagulant concentration (OCC) for making filled tofu. The objective of
      this study was to investigate the possible correlations between CPCC and the
      characteristics of soy milk made from various soybean samples and the effect of
      soy milk cooking and dilution conditions on CPCC. CPCC was determined by a
      titration method. Calcium chloride and magnesium chloride were used as
      coagulants. Soy milk characteristics including solid, protein, phytate, pH,
      titratable acidity, mineral content, and 11S/7S protein and these characteristics
      as affected by heating rate, heating time, and sequence of dilution and heating
      were studied. The results showed that the CPCC was significantly (p < 0.05)
      positively correlated with phytate content (grams per gram of protein), pH, and
      7S protein content but negatively correlated with protein content, 11S protein
      content, 11S/7S ratio, titratable acidity, and original calcium content. Within
      the same soybean material, more proteins required more coagulant, but higher
      protein concentration during cooking resulted in less coagulant required by each
      gram of protein during coagulation. The CPCC decreased with increasing soy milk
      heating time or decreasing heating rate. The sequence of heating and diluting for
      preparing soy milk also had an effect on CPCC.

PMID- 15161208
TI  - Carotenoid profiles and consumer sensory evaluation of specialty carrots (Daucus
      carota, L.) of various colors.
AB  - Five different colored carrots were analyzed for their carotenoid profile and
      underwent sensory evaluation to determine consumer acceptance (n = 96). Four
      major carotenoids were identified and quantified by use of HPLC methods. High
      beta-carotene orange carrots were found to contain the greatest concentration of
      total carotenoids. Except for the white, all the carrots are a significant source
      of bioavailable carotenoids. Sensory evaluation showed the high beta-carotene
      orange and white carrots to be favored over the yellow, red, and purple carrots
      in both blind and nonblind treatments (P < 0.01). However, all the carrots were
      well accepted by the consumer panel. With this information, carrot growers should
      be encouraged to cultivate specialty carrots to provide sources of both vitamin A
      precursors and phytochemicals.

PMID- 15161209
TI  - Physical and sensory properties of dairy products from cows with various milk
      fatty acid compositions.
AB  - Dairy products from milk of cows fed diets rich in polyunsaturated fatty acids
      have a more health-promoting fatty acid composition and are softer but often have
      oxidized flavors. Dairy products made from cow's milk that has more- or less
      unsaturated fatty acid compositions were tested for differences in texture and
      flavor from those made from bulk-tank milk. The milk was manufactured into
      butter, vanilla ice cream, yogurt, Provolone cheese, and Cheddar cheese. The
      products were analyzed for fatty acid composition, physical properties, and
      flavor. Milk of cows with a more monounsaturated fatty acid composition yielded
      products with a more monounsaturated fatty acid composition that were softer and
      had a satisfactory flavor. Thus, selection of cows for milk fatty acid
      composition can be used to produce dairy products that are probably more
      healthful and have a softer texture.

PMID- 15161207
TI  - Chemical composition and glycemic index of Brazilian pine (Araucaria
      angustifolia) seeds.
AB  - The seeds of Parana pine (Araucaria brasiliensis syn. Araucaria angustifolia),
      named pinhao, are consumed after cooking and posterior dehulling, or they are
      used to prepare a flour employed in regional dishes. Native people that live in
      the South of Brazil usually consume baked pinhao. As a result of cooking, the
      white seeds become brown on the surface due to the migration of some tinted
      compounds present in the seed coat. In this work, the proximate composition,
      minerals, flavonoids, and glycemic index (GI) of cooked and raw pinhao seeds were
      compared. No differences in moisture, lipids, soluble fiber, and total starch
      after boiling were found. However, the soluble sugars and P, Cu, and Mg contents
      decreased, probably as a consequence of leaching in the cooking water. Also, the
      boiling process modified the profile of the phenolic compounds in the seeds. No
      flavonols were detected in raw pinhao seeds. The internal seed coat had a
      quercetin content five times higher than that of the external seed coat; also,
      quercetin migrated into the seed during cooking. The internal seed coat had a
      high content of total phenolics, and seeds cooked in normal conditions (with the
      seed coat) showed a total phenolics content five times higher than that of seeds
      cooked without the seed coat. Cooking was then extremely favorable to pinhao
      seeds bioactive compounds content. The carbohydrate availability was evaluated in
      a short-term assay in humans by the GI. The GI of pinhao seeds cooked with the
      coat (67%) was similar to that of the seeds cooked without a coat (62%) and lower
      than bread, showing that cooking does not interfere with starch availability. The
      low glycemic response can be partly due to its high content of resistant starch
      (9% of the total starch).

PMID- 15161210
TI  - Comparison between cachaca and rum using pattern recognition methods.
AB  - The differentiation between cachaca and rum using analytical data referred to
      alcohols (methanol, propanol, isobutanol, and isopentanol), acetaldehyde, ethyl
      acetate, organic acids (octanoic acid, decanoic acid, and dodecanoic acid),
      metals (Al, Ca, Co, Cu, Cr, Fe, Mg, Mn, Ni, Na, and Zn), and polyphenols
      (protocatechuic acid, sinapaldehyde, syringaldehyde, ellagic acid, syringic acid,
      gallic acid, (-)-epicatechin, vanillic acid, vanillin, p-coumaric acid,
      coniferaldehyde, coniferyl alcohol, kaempferol, and quercetin) is described. The
      organic and metal analyte contents were determined in 18 cachaca and 21 rum
      samples using chromatographic methods (GC-MS, GC-FID, and HPLC-UV-vis) and
      inductively coupled plasma atomic emission spectrometry, respectively. The
      analytical data of the above compounds, when treated by principal component
      analysis, hierarchical cluster analysis, discriminant analysis, and K-nearest
      neighbor analysis, provide a very good discrimination between the two classes of
      beverages.

PMID- 15161212
TI  - Inductively coupled plasma optical emission spectrometric determination of
      minerals in thyme honeys and their contribution to geographical discrimination.
AB  - Twenty-four Spanish thyme honey samples were analyzed using inductively coupled
      plasma optical emission spectrometry (ICP-OES). Twenty-four minerals were
      quantified for each honey. The elements Al, As, Ba, Ca, Cr, Cu, Fe, K, Li, Mg,
      Mn, Na, P, Pb, S, Se, Si, Sr, and Zn were detected in all samples; seven elements
      are very abundant (Ca, K, Mg, Na, P, S, and Si), and six are not abundant (Al,
      Cu, Fe, Li, Mn, and Zn). Eleven of them are trace elements (As, Ba, Cd, Co, Cr,
      Ni, Mo, Pb, Se, Sr, and V) at <1 mg kg(-)(1). Classification of thyme honeys
      according to their origin (coast, mountains) was achieved by pattern recognition
      techniques on the mineral data. By means of principal component analysis, a good
      separation by geographical origin is obtained when scores for the two first
      principal components are plotted. Classification functions of 11 metals (Al, As,
      Cr, Cu, K, Li, Mg, Na, P, S, and V) were obtained using stepwise discriminant
      analysis and applied to classify correctly approximately 100% of the honey
      samples.

PMID- 15161211
TI  - Influence of harvest date and crop yield on the fatty acid composition of virgin
      olive oils from cv. Picual.
AB  - In this study was analyzed the effect of crop year and harvesting time on the
      fatty acid composition of cv. Picual virgin olive oil. The study was carried out
      during the fruit ripening period for three crop seasons. The mean fatty acid
      composition of Picual oils was determined. The oils contained palmitic acid
      (11.9%), oleic acid (79.3%), and linoleic acid (2.95%). The content of palmitic
      acid and saturated fatty acids decreased during fruit ripening while oleic and
      linoleic acids increased. The amount of stearic and linolenic acids decreased.
      The amount of saturated acids, palmitic and stearic, and the polyunsaturated
      acids linoleic and linolenic was dependent on the time of harvest, whereas the
      amount of oleic acid varied with the crop year. The differences observed between
      crop years for both palmitic and linoleic acid may be explained by the
      differences in the temperature during oil biosynthesis and by the amount of
      summer rainfall for oleic acid content. A significant relationship was observed
      between the MUFA/PUFA ratio and the oxidative stability measured by the Rancimat
      method.

PMID- 15161213
TI  - 1H NMR studies on Italian balsamic and traditional balsamic vinegars.
AB  - In the present work Principal Component Analysis applied to (1)H NMR spectra of
      balsamic and traditional balsamic vinegars is used to establish a simple and
      rapid aging determination protocol. Chemical composition of vinegar is dominated
      by carbohydrates even though several small components can be clearly observed in
      the proton NMR spectrum. Quantitative determination of some selected metabolites
      such as ethanol, acetic acid, malic acid, glucose, and HMF, considered as
      potential aging indicators, has been performed. (1)H NMR spectroscopy provides
      noninvasive characterization of such compounds, and our data demonstrate the
      validity of this approach, giving very promising results for assessing the
      quality of the final product.

PMID- 15161214
TI  - Effect of the epicuticular waxes of fruits and vegetables on the photodegradation
      of rotenone.
AB  - The effect of epicuticular waxes extracted from fruits (apple, nectarine, pear,
      and plum) and vegetables (tomato and eggplant) on the photodegradation of
      rotenone was studied. The waxes affected the decay rate and the degradation
      pathway of this botanical insecticide. Tomato, nectarine, and plum waxes
      decreased the photodegradation rate compared to controls, whereas apple and pear
      waxes increased it. Rotenone irradiated under sunlight without waxes gave seven
      photoproducts; in contrast, in the presence of waxes it changed its behavior,
      leading to different pathways according to the wax employed. The main
      photoproduct formed was 12abeta-rotenolone.

PMID- 15161215
TI  - A study on perchlorate exposure and absorption in beef cattle.
AB  - Perchlorate exposure and potential effects were evaluated in large mammals by
      monitoring heifer calves placed on a site with access to streamwater fed by a
      perchlorate-contaminated groundwater spring ( approximately 25 ng/mL). Blood was
      collected from the two calves on the site (and two control calves from an
      uncontaminated site) approximately every 2 weeks for analysis of perchlorate
      residues and thyroid hormones. During the 14 week study, perchlorate was detected
      (detection limit = 13.7 ng/mL) in blood plasma twice (15 ng/mL and 22 ng/mL) in
      one of the heifer calves drinking perchlorate-contaminated water on consecutive
      sampling periods 4 and 6 weeks after the beginning of perchlorate exposure.
      Constant exposure to 25 ppb perchlorate in drinking water had no effect on
      circulating thyroid hormones (T(3) and T(4)) in the heifer calves.

PMID- 15161216
TI  - Azimsulfuron sorption--desorption on soil.
AB  - The sorption and desorption of the herbicide azimsulfuron, N-[[(4
      dimethoxypyrimidin-2-yl)amino]carbonyl]1-methyl-4-(2-methyl-2H-tetrazole-5-yl)1H
      pyrazole-5-sulfonamide, were studied using five soils. Sorption isotherms
      conformed to the Freundlich equation. It was found that pH is the main factor
      influencing the sorption and that the sorption on soils was negatively correlated
      with pH. The highest level of sorption was measured on soils with low pH and high
      organic carbon content. Moreover, inorganic soil colloids, for example, smectite
      clay minerals and iron oxides, contributed to the sorption of azimsulfuron.
      Desorption was hysteretic on soils with high organic and inorganic colloid
      contents.

PMID- 15161217
TI  - Polyphenol glucosylating activity in cell suspensions of grape (Vitis vinifera).
AB  - Stilbenes are phenolic molecules that have antifungal effects in the plant and
      antioxidant and anti-cancer effects when consumed in the human diet.
      Glycosylation of stilbenes increases their solubility and may make them more
      easily absorbed by the intestine. We have found an activity in extracts of
      cultured cells of Vitis vinifera (cv. Gamay Freaux) that glucosylates the
      stilbene resveratrol to form piceid. The Km for UDP-Glucose was 1.2 mM, and the
      Km for resveratrol was 0.06 mM, values similar to those of other phenolic
      glucosyltransferases. We investigated the resveratrol glucosylating activity of
      the enzyme extracted from cells grown under different light treatments (dark,
      visible light, light + ultraviolet (UVC) radiation) and found the activity to be
      unaffected or slightly reduced. In contrast, UVC light strongly stimulated
      extractable quercetin glucosyltransferase activity. These results, combined with
      analysis of phenolic compounds extracted from the differently treated cells,
      suggest that the resveratrol glucosyltransferase is distinct from the
      glucosyltransferase(s) active on other phenolics.

PMID- 15161218
TI  - Fate of enrofloxacin in swine sewage.
AB  - The fate of enrofloxacin present in raw sewage at a swine-breeding facility was
      investigated by liquid-liquid extraction and reversed-phase liquid chromatography
      with photodiode array detection. Samples were collected in the storage pits of
      each pigsty and in a nonaerated lagoon used to stock the sewage. In the pigsties,
      the sewage was mixed with 10% olive oil groundwater, following a certified
      procedure (cod. Cer 020301) which reduces the bad odors and produces a better
      manure. This sewage treatment for 8 months in the lagoon dramatically reduced the
      amount of enrofloxacin to levels under the detection limit of 0.6 microg.L(-)(1).
      The results stress the importance of correct sludge management in limiting the
      impact of enrofloxacin in the environment.

PMID- 15161219
TI  - Flavor perception and aroma release from model dairy desserts.
AB  - Six model dairy desserts, with three different textures and two sucrose levels,
      were equally flavored with a blend of four aroma compounds [ethyl pentanoate,
      amyl acetate, hexanal, and (E)-2-hexenal] and evaluated by a seven person panel
      in order to study whether the sensory perception of the flavor and the aroma
      release during eating varied with the textural characteristics or the sweetness
      intensity of the desserts. The sensory perception was recorded by the time
      intensity (TI) method, while the in vivo aroma release was simultaneously
      measured by the MS-nose. Considering the panel as a whole, averaged flavor
      intensity increased with sucrose level and varied with the texture of the
      desserts. Depending on the aroma compound, the averaged profile of in vivo aroma
      release varied, but for each aroma compound, averaged aroma release showed no
      difference with the sucrose level and little difference with the texture of the
      desserts. Perceptual sweetness-aroma interactions were the main factors
      influencing perception whatever the texture of the desserts.

PMID- 15161220
TI  - Composition and functional properties of the essential oil of amazonian basil,
      Ocimum micranthum Willd., Labiatae in comparison with commercial essential oils.
AB  - Wild Amazonian basil Ocimum micranthum Willd. (O. campechianum Mill.) Labiatae
      essential oil was analyzed by GC and GC-MS: 31 compounds were identified. The
      main components were eugenol (46.55 +/- 5.11%), beta-caryophyllene (11.94 +/-
      1.31%), and beta-elemene (9.06 +/- 0.99%), while a small amount of linalool (1.49
      +/- 0.16%) was detected. The oil was tested for its in vitro food-related
      biological activities and compared with common basil Ocimum basilicum and Thymus
      vulgaris commercial essential oils. Radical scavenging activity was evaluated
      employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The oil exerted a good
      capacity to act as a nonspecific donor of hydrogen atoms or electrons when
      checked in the diphenylpicrylhydrazyl assay, quenching 76,61 +/- 0.33% of the
      radical, with values higher than those reported by reference oils. In the beta
      carotene bleaching test, the oil provided an antioxidant efficacy comparable with
      that of O. basilicum and T. vulgaris essential oils. These data were confirmed by
      photochemiluminescence, where the oil showed a remarkable antioxidant capacity
      (2.39 +/- 0.1), comparable to that of Trolox and vitamin E, and higher than the
      other essential oils. Antibacterial activity of O. micranthum essential oil was
      evaluated against Gram positive and Gram negative bacterial strains. The oil
      showed a dose-dependent antifungal activity against pathogenic and food spoiling
      yeasts.

PMID- 15161221
TI  - Influence of vine training and sunlight exposure on the 3-alkyl-2
      methoxypyrazines content in musts and wines from the Vitis vinifera variety
      cabernet sauvignon.
AB  - The influence of vine training and sunlight exposure on the 3-alkyl-2
      methoxypyrazines contents in musts and wines was studied by means of two
      previously reported methods based on headspace solid-phase micro-extraction.
      Experimental samples were monitored throughout grape ripening and wine making. 3
      Isobutyl-2-methoxypyrazine, 3-sec-butyl-2-methoxypyrazine and 3-isopropyl-2
      methoxypyrazine were identified. The 3-isobutyl-2-methoxypyrazine content
      decreased throughout grape ripening in all of the sample types studied. After 1
      day of maceration with the skins, there was an increase, but after racking, no
      further increase was observed. No significant differences between samples were
      found during grape ripening. Wines from goblet-trained vines, however, contained
      significantly less 3-isobutyl-2-methoxypyrazine. Clusters protected from sunlight
      since the beginning of the veraison resulted in wines with a significantly lower
      content of this compound than the control samples.

PMID- 15161222
TI  - Identification of the astringent taste compounds in black tea infusions by
      combining instrumental analysis and human bioresponse.
AB  - Application of taste dilution analyses on freshly prepared black tea infusions
      revealed neither the high molecular weight thearubigen-like polyphenols nor the
      catechins and theaflavins, but a series of 14 flavon-3-ol glycosides as the main
      contributors to the astringent taste perceived upon black tea consumption. Among
      these glycosides, the apigenin-8-C-[alpha-l-rhamnopyranosyl-(1-->2)-O-beta-d
      glucopyranoside] was identified for the first time in tea infusions. Depending on
      the structure, the flavon-3-ol glycosides were found to induce a velvety and
      mouth-coating sensation at very low threshold concentrations, which were far
      below those of catechins or theaflavins; for example, the threshold of 0.001
      micromol/L found for quercetin-3-O-[alpha-l-rhamnopyranosyl-(1-->6)-O-beta-d
      glucopyranoside] is 190000, or 16000 times below the threshold determined for
      epigallocatechin gallate or theaflavin, respectively. Moreover,
      structure/activity considerations revealed that, besides the type of flavon-3-ol
      aglycon, the type and the sequence of the individual monosaccharides in the
      glycosidic chain are key drivers for astringency perception of flavon-3-ol
      glycosides.

PMID- 15161223
TI  - Ionizing radiation and antioxidants affect volatile sulfur compounds, lipid
      oxidation, and color of ready-to-eat Turkey bologna.
AB  - Bologna was processed from ground turkey breast meats containing one of four
      antioxidant treatments (none, rosemary extract, sodium erythorbate, and sodium
      nitrite). After it was cooked, the bologna was sliced, sealed in gas impermeable
      bags, exposed to 0, 1.5, and 3.0 kGy gamma-radiation, and then stored at 5
      degrees C for up to 8 weeks. Thiobarbuturic acid reactive substances (TBARS),
      color, and volatile sulfur compounds were measured every 2 weeks during storage.
      Irradiation had no consistent effect on TBARS values. The rosemary extract and
      sodium nitrite inhibited, while erythorbate increased, TBARS values, independent
      of radiation dose or storage time. Irradiation promoted redness and reduced
      yellowness of the control (no antioxidant) bologna at weeks 0 and 2. The use of
      nitrite and rosemary extract inhibited the changes in color due to irradiation.
      Several volatile sulfur compounds (hydrogen sulfide, methanethiol, methyl
      sulfide, and dimethyl disulfide), measured using a pulsed flame photometric
      detector, increased with radiation dose. However, none of the antioxidants had
      any substantial effect on volatile sulfur compounds induced by irradiation. Our
      results suggest that antioxidants did not consistently affect irradiation-induced
      volatile sulfur compounds of turkey bologna although they did significantly
      impact color and lipid oxidation.

PMID- 15161224
TI  - Characterization of the aroma of a wine from maccabeo. Key role played by
      compounds with low odor activity values.
AB  - An extract from a dry young wine from Maccabeo was studied by aroma extract
      dilution analysis (AEDA), quantitative gas chromatography, and different sensory
      studies. In a first study, 53 different aroma compounds were quantified and used
      to prepare aroma models. 2-Methyl-3-furanthiol (FD = 16) and 4-methyl-4
      mercaptopentan-2-one (FD = 2), could not be quantified and were not included in
      those models, which were not very similar to the original wine. Omission tests
      did not show the existence of impact compounds. In another set of experiments,
      selected aroma chemicals were added to the original wine, but in only in two
      cases (isoamyl acetate and gamma-nonalactone) was a positive effect noted, on
      banana and citric notes, respectively. After these discouraging results, 4-methyl
      4-mercaptopentan-2-one and 2-methyl-3-furanthiol were quantified and included in
      the models. The concentration of the former was as low as 5 ng x L(-)(1) (odor
      threshold = 0.8 ng x L(-)(1)); however, its inclusion in the synthetic mixture
      had a significant effect, making it very close to the original wine. Its role was
      confirmed by omission tests. Results are briefly discussed.

PMID- 15161225
TI  - Synthesis and sensorial properties of 2-alkylalk-2-enals and 3-(acetylthio)-2
      alkyl alkanals.
AB  - Parallel synthesis was applied to prepare a series of 3-(acetylthio)-2-alkyl
      alkanals by Michael addition of thioacetic acid under alkaline conditions to
      alpha,beta-unsaturated 2-alkyl-substituted aldehydes, which were obtained by
      aldol condensation of the corresponding primary aldehydes as starting materials.
      The target compounds were characterized in terms of GC, MS, and NMR data. The
      sensory properties of the odorants, such as odor quality and odor detection
      threshold value, were determined with a trained panel. Structure-activity
      relationships are discussed, suggesting that the 1,3-oxygen-sulfur functionality,
      required for the "olfactophore" of tropical/vegetable notes, can further be
      extended to the acetylthio derivatives.

PMID- 15161226
TI  - chemical composition, plant genetic differences, antimicrobial and antifungal
      activity investigation of the essential oil of Rosmarinus officinalis L.
AB  - The chemical composition of the essential oil of the Sardinian Rosmarinus
      officinalis L. obtained by hydro distillation and steam?hydro distillation was
      studied using GC-FID and MS. Samples were collected at different latitude and
      longitude of Sardinia (Italy). The yields ranged between 1.75 and 0.48% (v/w,
      volume/dry-weight). A total of 30 components were identified. The major compounds
      in the essential oil were alpha-pinene, borneol, (-) camphene, camphor,
      verbenone, and bornyl-acetate. Multivariate analysis carried out on chemical
      molecular markers, with the appraisal of chemical, pedological, and random
      amplified polymorphic DNA data, allows four different clusters to be
      distinguished. The antimicrobial and antifungal tests showed a weak activity of
      Sardinian rosemary. On the other hand, an inductive effect on fungal growth,
      especially toward Fusarium graminearum was observed.

PMID- 15161227
TI  - Identification of monomenthyl succinate, monomenthyl glutarate, and dimenthyl
      glutarate in nature by high performance liquid chromatography-tandem mass
      spectrometry.
AB  - Menthol, menthone, and other natural compounds provide a cooling effect and a
      minty flavor and have found wide application in chewing gum and oral care
      products. Monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate
      provide a cooling effect without the burning sensation associated with menthol.
      Additionally, because they do not have a distinct flavor, they can be used in
      applications other than mint flavors. Because these menthyl esters have not been
      reported in nature, we undertook to identify a natural source for these cooling
      compounds. Using high performance liquid chromatography-tandem mass spectrometry,
      monomenthyl succinate was identified in Lycium barbarum and Mentha piperita, and
      monomenthyl glutarate and dimenthyl glutarate were identified in Litchi chinesis.
      The identifications were based on the correlation of mass spectrometric and
      chromatographic retention time data for the menthyl esters in the extracts with
      authentic standards which resulted in a 99.980% confidence in the
      identifications.

PMID- 15161228
TI  - Influence of lambda-carrageenan on the release of systematic series of volatile
      flavor compounds from viscous food model systems.
AB  - The effect of lambda-carrageenan addition level (0.1, 0.25, 0.4, and 0.5% w/w)
      and viscosity on the release of systematic series of aroma compounds (aldehydes,
      esters, ketones, and alcohols) was studied in thickened viscous solutions
      containing lambda-carrageenan and 10 wt % of sucrose. Air-liquid partition
      coefficients K (37 degrees C) of a total of 43 aroma compounds were determined in
      pure water and in the lambda-carrageenan solutions by static headspace gas
      chromatography. Mass transfer of the aroma compounds in water and in the
      thickened lambda-carrageenan solutions which had a wide viscosity range was
      assessed by dynamic headspace gas chromatography. K (37 degrees C) increased as
      the carbon chain increased within each homologous series. Esters exhibited the
      highest volatility, followed by aldehydes, ketones, and alcohols. Under
      equilibrium, no overall effect of lambda-carrageenan was found, except with the
      most hydrophobic compounds. Analysis of flavor release under nonequilibrium
      conditions revealed a suppressing effect of lambda-carrageenan on the release
      rates of aroma compounds, and the extent of decrease in release rates was
      dependent on the physicochemical characteristics of the aroma compounds, with the
      largest effect for the most volatile compounds. However, none of the effects was
      of a magnitude similar to the obtained changes in the macroscopic viscosity, and
      the suppressing effects are therefore attributable to the thickener and not the
      physical properties of the increasingly viscous systems.

PMID- 15161229
TI  - Complexation of whey proteins with carrageenan.
AB  - The formation of electrostatic complexes of whey protein (WP) and a nongelling
      carrageenan (CG) was investigated as a function of pH, ionic strength,
      temperature, and protein-to-polysaccharide (Pr:Ps) ratio. On lowering the pH, the
      formation of soluble WP/CG complexes was initiated at pH(c) and insoluble
      complexes at pH(phi), below which precipitation occurred. The values of the
      transition pH varied as a function of the ionic strength. It was shown that at
      [NaCl] = 45 mM, the value of pH(phi) was the highest, showing that the presence
      of monovalent ions was favorable to the formation of complexes by screening the
      residual negative charges of the CG. When CaCl(2) was added to the mixtures,
      complexes of WP/CG were formed up to pH 8 via calcium bridging. The electrostatic
      nature of the primary interaction was confirmed from the slight effect of
      temperature on the pH(phi). Increasing the Pr:Ps ratio led to an increase of the
      pH(phi) until a ratio of 30:1 (w/w), at which saturation of the CG chain seemed
      to be reached. The behavior of WP/CG complexes was investigated at a low Pr:Ps
      ratio, when the biopolymers were mixed directly at low pH. It resulted in an
      increase of the pH of the mixture, as compared to the initial pH of the separate
      WP and CG solutions. The pH increase was accompanied by a decrease in
      conductivity. The trapping of protons inside the complex probably resulted from a
      residual negative charge on the CG. If NaCl was present in the mixture, the
      complex took up the Na(+) ions instead of the H(+) ions.

PMID- 15161231
TI  - Use of near-infrared spectroscopy for screening the individual and total
      glucosinolate contents in Indian mustard seed (Brassica juncea L. Czern. &
      Coss.).
AB  - The potential of near-infrared spectroscopy (NIRS) for screening the sinigrin,
      gluconapin, 4-hydroxyglucobrassicin, and total glucosinolate contents of Indian
      mustard (Brassica juncea L. Czern. & Coss.) seed was assessed. Intact seed
      samples of this species were analyzed by NIRS and their reference values
      regressed against different spectral transformations by modified partial least
      squares (MPLS) regression. The coefficients of determination (r (2)) for
      sinigrin, gluconapin, 4-hydroxyglucobrassicin, and total glucosinolate contents
      were, respectively, 0.86, 0.95, 0.33, and 0.82. The standard deviation to
      standard error of prediction (SEP) ratio, and SEP to standard error of laboratory
      ratio were for these constituents as follows: sinigrin, 2.59 and 2.70;
      gluconapin, 4.16 and 2.08; 4-hydroxyglucobrassicin, 1.18 and 1.40; and total
      glucosinolates, 2.18 and 1.60. By comparison of commercial sinigrin spectrum with
      the first MPLS loadings of the sinigrin equation, it can be concluded that the
      molecule of sinigrin has a specific signal in the seed spectrum of Brassica.

PMID- 15161230
TI  - Cell wall polysaccharides from chalkumra (Benincasa hispida) fruit. Part I.
      Isolation and characterization of pectins.
AB  - Pectic polysaccharides were obtained from chalkumra (Benincasa hispida) fruit by
      sequential extraction with ammonium oxalate (fraction BOX), dilute acid (fraction
      BHCl), and cold dilute alkali (fraction BOH). The highest yield of
      polysaccharides was obtained with oxalate and HCl. BOX was enriched in partly
      methyl-esterified galacturonic acid, whereas BHCl and BOH contained mostly
      galactose. All of the extracts showed similar elution patterns in size exclusion
      chromatography although the intrinsic viscosities (eta) were different (132 +/-
      6, 100 +/- 5, and 285 + 10 mL/g for BOX, BHCl, and BOH, respectively). From
      fractionation by anion exchange chromatography, homogalacturonan (as seen from
      sugar analysis and Fourier transform infrared spectrum) accounted for more than
      half of BOX and 11% of BHCl. Methylation analyses and hydrolysis of BHCl with
      endo-beta-(1-->4)-d-galactanase showed the presence of beta-(1-->4)-d-galactan.
      The neutral galactan represented more than 76% of BHCl and approximately 40% of
      BOH. The other polysaccharides were complex galactans in BOH and an acidic
      arabinan (<1%) in BOX and BHCl.

PMID- 15161232
TI  - Effects of heating on the interaction of lipid and zein in a dry powder system.
AB  - The effects of heat treatment on the interaction of lipid and zein in a dry
      powder system were investigated. Linolenic acid ethyl ester (LAE) was mixed with
      the zein powder. The glass transition temperature (T(g)) for the dry powder zein
      was shown to be approximately 107 degrees C by differential scanning calorimetry.
      The thermogram of the zein-LAE mixed powder showed an exothermic transition near
      the T(g) of zein. Fourier transform infrared (FT-IR) spectroscopy was used for
      detecting the structural changes in zein by heat treatment, that is, elevating
      the temperature from 25 to 160 degrees C. The heat treatment of the powdery zein
      with and without LAE caused increases in the alpha-helix, beta-turn, and beta
      sheet, concomitant with decreases in the intermolecular hydrogen-bonded beta
      sheet and random coil. Such changes in the secondary structure were more drastic
      for the powder with LAE. The heating of the zein-LAE mixed powder also caused
      decreases in the peaks originating from LAE in the FT-IR spectra. These results
      suggest that the heat treatment induced the interaction of the zein and LAE in
      the powdery system. The influence of heating on the antioxidative activity of dry
      powder zein was studied by measurements of the peroxide value. When zein-LAE
      mixed powder was heated before storage, the oxidation of LAE was inhibited for 7
      days, whereas LAE was oxidized within 1 day in the absence of heat treatment.

PMID- 15161233
TI  - Redox-related cytotoxic responses to different casein glycation products in Caco
      2 and int-407 cells.
AB  - Sugar-casein glycation products (GPs) were generated by Maillard reaction (MR)
      with different monosaccharide sources [e.g., glucose (Glc), fructose (Fru), and
      ribose (Rib)] and prolonged heating (e.g., 27 days at 55 degrees C) to produce
      Maillard reaction products (MRPs) that varied in opponent (L, a, b) color
      measurement and changes in pH, available lysine, and amino-sugar ratio. Theses
      results signified different rates of three sugar and casein glycation. Sugar
      casein GPs from aldohexose, ketohexose, and aldopentose sugar sources were
      recovered on day 18 of heating and compared for bioactive properties using human
      embryonic intestinal cell (Int-407) and adenocarcinoma cell (Caco-2) lines. Glu-
      and Fru-casein GPs produced significant (p < 0.05) decreases in antioxidant
      superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase
      enzyme activities in the Int-407 cell line, whereas no effect on antioxidant
      enzymes was obtained from Rib-casein GP. Moreover, the Caco-2 cell antioxidant
      enzyme status was not affected by the presence of sugar-casein GPs, regardless of
      sugar source. The reduction in antioxidant enzyme activity of Int-407 cells by
      Glu and Fru- casein GPs corresponded to a significant (p < 0.05) reduction in Int
      407 cell viability. In contrast, no change in Caco-2 cell viability was observed
      with sugar-casein GP. This finding demonstrates that the noted variable
      cytotoxic, sugar specific effects of casein GP were related to reductions in
      critical antioxidant enzyme activities. Moreover, the source of intestinal cell
      line was an important factor to show the effect of sugar-casein GPs on redox
      related cytotoxicity.

PMID- 15161234
TI  - Polyphenolic compounds, antioxidant capacity, and quinone reductase activity of
      an aqueous extract of Ardisia compressa in comparison to mate (Ilex
      paraguariensis) and green (Camellia sinensis) teas.
AB  - Aqueous extracts of the leaves of Ardisia compressa (AC) have been used in folk
      medicine to treat various liver disorders including liver cancer. The objective
      of this study was to partially characterize and determine the total polyphenol
      content, antioxidant capacity, and quinone reductase activity of A. compressa tea
      in comparison to mate (Ilex paraguariensis, MT) and green (Camellia sinensis,GT)
      teas. Total polyphenol content, antioxidant capacity, and phase II enzyme
      induction capacity were measured by the modified Folin-Ciocalteu, ORAC, and
      quinone reductase (QR) assays, respectively. The major polyphenols in AC were not
      catechins. HPLC retention times and standard spikes of AC indicated the presence
      of gallic acid, epicatechin gallate, ardisin and kaempferol. Using catechin as
      standard, the total polyphenol value of AC (36.8 +/- 1.1 mg/mg DL) was
      significantly lower than GT (137.2 +/- 5.8 mg equivalent of (+)-catechin/mg dried
      leaves, DL) and MT (82.1 +/- 3.8 mg/mg DL) (P < 0.001). Antioxidant capacity (AC,
      333; GT, 1346; MT, 1239 mmol Trolox equivalents/g DL) correlated with total
      polyphenol values (r(2) = 0.86, P < 0.01). AC (4.5-12.5 microg/mL) induced QR
      enzyme, in Hepa1c1c7 cells, up to 15%. MT and GT showed no induction at the
      concentrations tested (0.5-10.5 and 0.5-12.5 mg/mL, respectively). These results
      suggest that AC has a different mechanism of protection against cytotoxicity that
      is not related to its antioxidant capacity. Further studies are needed to
      determine such mechanisms and to explore its potential as a chemopreventive or
      therapeutic agent.

PMID- 15161235
TI  - Evolution of robusta green coffee redox enzymatic activities with maturation.
AB  - Oxidation reactions in coffee involve redox-sensitive polyphenols and appear to
      control the fragmentation of coffee storage proteins both in solution and during
      roasting. Coffee-specific nitrogenous flavor precursors may derive from this
      process. Accordingly, data converge to suggest that the redox status of the green
      bean before roasting might control the development of subsequent redox reactions
      during roasting. Consequently, we decided to identify biological events that may
      trigger or prevent oxidation during maturation of the coffee cherry and set the
      final redox status of the green bean. In a previous study, we observed that the
      sensitivity of green coffee to oxidative processes decreased along maturation. By
      using the very same samples originating from open-pollinated Robusta clones, we
      followed the activity of three essential redox enzymes: catalase (CAT),
      peroxidase (POD) and polyphenoloxidase (PPO). While CAT and POD activities
      increased with maturation, PPO activities decreased. Thanks to the identification
      of an atypical immature subclass, it appeared that CAT might be an essential
      factor in setting the final redox status of the green bean before the roasting
      event.

PMID- 15161236
TI  - Production and characterization of O/W emulsions containing droplets stabilized
      by lecithin-chitosan-pectin mutilayered membranes.
AB  - The possibility of producing stable oil-in-water (O/W) emulsions containing oil
      droplets surrounded by multiple layer interfacial membranes from food grade
      ingredients has been demonstrated. These emulsions were produced using a three
      stage process that relies on the adsorption of charged biopolymers to oppositely
      charged surfaces. Emulsions (0.5 wt % corn oil, 0.1 wt % lecithin, 0.0078 wt %
      chitosan, 0.02 wt % pectin, and 100 mM acetic acid, pH 3.0) containing oil
      droplets stabilized by lecithin-chitosan-pectin membranes were formed using this
      interfacial layer-by-layer deposition process. The droplets in these emulsions
      had good stability to aggregation over a wide range of pH values and salt
      concentrations (pH 4-8 at 0 mM NaCl and pH 3-8 at 100 mM NaCl). This technology
      could be extremely useful to the food industry for the creation of O/W emulsions
      with improved properties or novel applications, e.g., improved stability to
      environmental stresses, protection of labile substances, controlled release, and
      triggered release.

PMID- 15161237
TI  - Effects of paprika pigments on oxidation of linoleic acid stored in the dark or
      exposed to light.
AB  - We examined the antioxidant effects of paprika pigments on oxidation of linoleic
      acid and on decoloration of the sample when stored at 37 degrees C in the dark or
      exposed to fluorescent light for 8 h per day. (1)H nuclear magnetic resonance
      with dioxane as an external proton reference was used to estimate the oxidative
      deterioration of linoleic acid. Oxidation was estimated by observing the ratio of
      the divinylmethylene proton signal area in linoleic acid vs the proton signal
      area in dioxane. The addition of paprika pigments suppressed the oxidation of
      linoleic acid during storage in the dark, and the effect was markedly increased
      with increasing concentrations (0.02, 0.2, and 2%). When the linoleic acid with
      added paprika pigments was exposed to light, only a slight suppression of
      oxidation was observed, and the color of the sample disappeared more rapidly than
      that in the dark. At the time of decoloration of the sample with added pigments,
      considerable oxidation of linoleic acid occurred. As the color change is due to
      degradation of the pigment, an increase in oxidation at the time of discoloration
      is consistent with the pigments functioning as antioxidants. The addition of
      alpha-tocopherol to paprika pigments stabilized degradation of the pigments by
      light. Although the addition of alpha-tocopherol to linoleic acid with added
      paprika pigments prolonged the decoloration of the sample under light, the
      prevention of oxidation under the light condition was not as effective as for the
      samples stored in the dark.

PMID- 15161238
TI  - Active oxygen detoxifying enzymes and phenylalanine ammonia-lyase in the ethylene
      induced chilling tolerance in citrus fruit.
AB  - The effects of applying ethylene (2 microL x L(-)(1)) during cold storage of
      Fortune mandarins on the development of chilling-induced peel damage and on
      changes in the activities of the enzymes of the antioxidant system, superoxide
      dismutase, catalase (CAT), ascorbate peroxidase, guaiacol peroxidase, and
      glutathione reductase, and on phenylalanine ammonia-lyase (PAL) have been
      investigated. Chilling damage was reduced by applying ethylene during fruit
      storage at 1.5 degrees C. PAL activity increased in response to cold stress and
      was higher in fruit held under ethylene than under air during the whole storage
      period, whereas CAT was temporarily higher in ethylene-treated fruit. In
      contrast, the activities of the other enzymes were not increased by ethylene. The
      global results suggest that the ethylene-induced chilling tolerance in Fortune
      mandarins might be due to increased PAL and CAT activities.

PMID- 15161239
TI  - Glycosylation modification improved the characteristics of recombinant chicken
      cystatin and its application on mackerel surimi.
AB  - The recombinant and glycosylation chicken cystatins were expressed and secreted
      in the broth of Pichia pastoris X-33 transformant with apparent molecular masses
      (M) of 14 and 55 kDa, respectively. The glycosylation cystatin (glycocystatin)
      contained a polysaccharide chain that was composed of 50 DP of mannose residues.
      Because of the polymannosyl chain, the inhibitory ability in glycocystatin was
      90.8% of recombinant cystatin. In addition to freeze-thawing stability, the
      thermal and pH stabilities as well as the susceptibility of glycocystatin were
      also enhanced. Both cystatins could improve the mackerel surimi gel by inhibiting
      the gel softening, which was derived from the hydrolysis of catheptic cysteine
      proteinases. Despite the additional amount of glycocystatin (8 units), twice that
      of recombinant cystatin, the 40 and 15% increases in breaking force and
      deformation of gels were also observed. Accordingly, the surimi gel was further
      improved by enhancing the stability of chicken cystatin.

PMID- 15161240
TI  - Interactive effects of microbial transglutaminase and recombinant cystatin on the
      mackerel and hairtail muscle protein.
AB  - Interactive effects of microbial transglutaminase (MTGase) and recombinant
      cystatin on the mackerel and hairtail water soluble protein (WSP), salt soluble
      protein (SSP), and muscle protein (MP) were investigated. According to sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and enzymic activity analyses,
      cross-linking of mackerel and hairtail myosin heavy chain and low molecular mass
      compounds and formation of epsilon-(gamma-glutamyl)lysine cross-links were
      observed on samples with MTGase, while the recombinant cystatin could effectively
      inhibit the cathepsins and subsequently prevent degradation of proteins during
      setting. The cathepsins and MTGase activities in WSP, SSP, and MP solutions
      decreased, but the recombinant cystatin activity increased during setting at 45
      degrees C.

PMID- 15161241
TI  - Influence of pH and iota-carrageenan concentration on physicochemical properties
      and stability of beta-lactoglobulin-stabilized oil-in-water emulsions.
AB  - The influence of pH and iota-carrageenan concentration on the properties of beta
      lactoglobulin (beta-Lg)-stabilized oil-in-water emulsions was investigated by
      measuring the particle charge, particle size distribution, and creaming
      stability. Emulsions containing droplets stabilized by beta-Lg were produced by
      homogenization, and then, iota-carrageenan was added. At pH 3, the droplet charge
      did not change for iota-carrageenan concentrations <or=0.1 wt % but decreased
      rapidly at high concentrations, while the mean particle diameter increased
      slightly as the iota-carrageenan concentration was increased. These results
      suggest that the interaction between iota-carrageenan and beta-Lg was weak at pH
      3 probably because some sulfate groups were protonated (pK(a) = 2). At pH 4 and
      pH 5, the droplet charge decreased dramatically as the iota-carrageenan
      concentration was increased from 0 to 0.15 wt %, but droplet aggregation and
      creaming occurred in the emulsions, indicating that interfacial complexes between
      iota-carrageenan and beta-Lg could not stabilize the emulsions, probably due to
      bridging flocculation. At pH 6, the droplet charge in the primary emulsions was
      negative and became more negative as the iota-carrageenan concentration was
      increased. The mean particle diameter was relatively small at all iota
      carrageenan concentrations, and emulsions were stable to creaming after 1 week of
      storage. We propose that carrageenan adsorbed to the droplet surfaces and
      increased the electrostatic repulsion between droplets. At pH 7 and pH 8, the
      droplet charge did not change as the iota-carrageenan concentration was
      increased, but these emulsions became unstable to creaming above a critical
      carrageenan concentration, which was attributed to depletion flocculation.

PMID- 15161243
TI  - Physiological difference between free and triglyceride-type conjugated linoleic
      acid on the immune function of C57BL/6N mice.
AB  - Previous studies have shown the physiological significance of dietary conjugated
      linoleic acid (CLA) in various experimental animals and in human beings. One of
      the important problems to better elucidate is the difference between triglyceride
      (TG) and free (FFA) dietary CLA. Here, using splenocytes, this study assesses how
      TG- and FFA-CLA modulate immunoglobulin and various cytokine productions. In this
      study, C57BL/6N mice were fed an experimental diet containing 0% CLA, 0.1 or 1%
      FFA-CLA, or 0.1 or 1% TG-CLA for 3 weeks. The production of immunoglobulin tended
      to be up-regulated by 1% FFA-CLA. As a result of protein array analysis using the
      supernatant from splenocytes cultured with no CLA, 1% FFA-CLA, and TG-CLA, some
      cytokine production was shown to be remarkably regulated by dietary FFA- and TG
      CLA. A total of 32 cytokines were examined, and 11-14 produced cytokines that
      were 2-fold up-regulated as compared with control for FFA- or TG-CLA,
      respectively. Especially, the production of IL-9 and MCP-5 and other cytokines
      was remarkably up-regulated by both FFA- and TG-CLA. In addition, seven cytokines
      were 2-fold down-regulated by TG-CLA. These data show that there is a slight but
      significant difference between the functionalities of FFA- and TG-CLA.

PMID- 15161242
TI  - Changes in trout hemoglobin conformations and solubility after exposure to acid
      and alkali pH.
AB  - The effect of different acid and alkali treatments followed by pH readjustment on
      solubility and conformation of trout hemoglobins was investigated. At low pH (1.5
      3.5) hemoglobin was unfolded at faster rates as the pH was lowered. Inclusion of
      500 mM NaCl at low pH significantly increased the rate of unfolding. At alkaline
      pH (10-12) the conformation of hemoglobin was much less affected than at acid pH,
      and the presence of salt had little additional effect. When hemoglobin solutions
      were adjusted to neutrality at different stages of unfolding, the recovery of
      native structure on refolding was proportional to the extent of unfolding prior
      to pH readjustment: the more unfolded the protein, the less was the recovery of
      native structure. The presence of salt led to a smaller recovery of native
      structure. The more improperly unfolded the hemoglobin was (and hydrophobic), the
      lower was its solubility. Results suggest that the presence of NaCl (25-500 mM)
      may not only interfere with the refolding process but also enhance the
      hydrophobic interactions of improperly refolded hemoglobin, possibly due to
      charge screening. These results show that proper control of unfolding and
      refolding time and ionic strength in processes using highly acidic or alkaline
      conditions can minimize loss of hemoglobin solubility.

PMID- 15161245
TI  - Radicinols and radicinin phytotoxins produced by Alternaria radicina on carrots.
AB  - The phytotoxin epi-radicinol, a diastereomer of radicinol, was isolated from
      large cultures of Alternaria radicina grown on carrot slices and identified by GC
      MS, LC-MS, (1)H NMR, and (13)C NMR. Four strains of A. radicina isolated from
      rotted carrot produced epi-radicinol as the major metabolite (up to 39414
      microg/g) together with radicinol (up to 2423 microg/g), and, to a lesser extent,
      radicinin when cultured on carrot slices, whereas on rice they mainly produced
      radicinin (2486-53800 microg/g). Radicinin and epi-radicinol reduced root
      elongation of germinating carrot seeds at concentrations of 10-20 microg/mL.
      Carrot samples naturally infected by A. radicina contained detectable quantities
      of epi-radicinol also in combination with lower levels of radicinin or radicinol.
      Accumulation of radicinols and radicinin in stored carrots, either naturally
      contaminated or artificially inoculated with A. radicina, was stimulated by
      successive temperature rises from 1 to 10 degrees C and from 10 to 20 degrees C,
      reaching maximum levels of 60 microg/g epi-radicinol and 26 microg/g radicinin.
      This is the first report on the production of radicinols by A. radicina and its
      natural occurrence in carrots in association with radicinin.

PMID- 15161244
TI  - Effect of olive ripening degree on the oxidative stability and organoleptic
      properties of cv. Nostrana di Brisighella extra virgin olive oil.
AB  - The evaluation of the influence of olive ripening degree on the stability of
      extra virgin olive oils by the determination of the oxidative stability index,
      the DPPH(*) radical test, and the quali-quantitative analysis of phenolic
      compounds, as well as the study of the variation of their sensory profiles, plays
      a key role in the assessment of the overall olive oil quality. Olives of the cv.
      Nostrana di Brisighella grown in the north-central Italian region of Emilia
      Romagna were picked at four different stages of ripeness and immediately
      processed in an experimental mill. The polar extracts of oil samples were
      submitted to spectrophotometric analysis of total phenols and o-diphenols and to
      liquid chromatographic determination of their quali-quantitative profile (HPLC
      DAD/MSD). To attain a complete description of oil samples, fatty acid
      composition, ultraviolet indices (K(232), K(270), and deltaK), free acidity
      degree, and peroxide value were also determined according to the European Union
      methods stated in Regulation 2568/91 (1, Off. J. Eur. Communities 1991, L248, 1
      82). Sensory quantitative descriptive analysis (QDA) and triangular tests were
      performed to establish the influence of olive ripening degree on the resulting
      oil's organoleptic properties. The evolution of the analytical parameters studied
      shows that the ripeness stage of Nostrana di Brisighella olives that yields the
      best oil corresponds to a Jaen index value between 2.5 and 3.5. Oils produced
      from olives harvested within this time frame present a superior sensory profile
      accompanied by the highest possible chemical and nutritional properties.

PMID- 15161246
TI  - Green and black teas inhibit atherosclerosis by lipid, antioxidant, and
      fibrinolytic mechanisms.
AB  - Tea is the most widely consumed beverage in the world, second only to water. Most
      laypersons and scientists believe that green tea is healthier than black tea due
      to the low incidence of heart disease and cancer in the Orient. Here, we report
      the first dose-response comparison of a green and black tea on normal hamsters
      after long-term supplementation and on a hamster model of atherosclerosis. Both
      teas were equally effective in inhibiting atherosclerosis with the lower dose
      decreasing it 26-46% and the high dose decreasing it 48-63%. Atherosclerosis was
      inhibited by three mechanisms: hypolipemic, antioxidant, and antifibrinolytic.
      There was a significant correlation between atherosclerosis and the three
      mechanisms. In the normal animals, teas also caused some improvement in plasma
      low density lipoprotein (LDL), LDL/high density lipoprotein ratio, triglycerides,
      lipid peroxides, lower density lipoprotein lipid peroxides, and fibrinogen.
      Isolated lower density lipoprotein oxidizability was also reduced in all groups.
      Green and black teas were equally effective at human equivalent doses, thus
      confirming human intervention and epidemiology studies and providing mechanisms
      for teas' benefit.

PMID- 15161247
TI  - Alkali extraction of beta-d-glucans from Saccharomyces cerevisiae cell wall and
      study of their adsorptive properties toward zearalenone.
AB  - The isolated cell wall of Saccharomyces cerevisiae has some capacity to adsorb
      zearalenone (affinity near 30%) and reduce the bioavailability of toxins in the
      digestive tract. The adsorption process was quantified in vitro, and the data
      obtained when plotted with Hill's equation indicated a cooperative process. The
      model showed that the adsorption capacity was related to the yeast cell wall
      composition. This work focused on the role of various beta-d-glucan types in the
      efficacy of zearalenone adsorption by yeast cell wall and sought to elucidate
      some of the adsorption mechanisms. Zearalenone was mixed at 37 degrees C with a
      constant quantity of alkali-soluble or alkali-insoluble beta-d-glucans isolated
      from yeast cell walls, and the amount of adsorbed zearalenone was measured. Given
      that the alkali solubility of beta-d-glucans is a determining factor for their
      three-dimensional conformation and that the alkali-insoluble fraction had a
      greater affinity (up to 50%) than the alkali-soluble fraction ( approximately
      16%), it was concluded that the three-dimensional structure strongly influences
      the adsorption process. The alkali insolubility of beta-d-glucans led to the
      formation of single and/or triple helices, which have been identified as the most
      favorable structures for zearalenone adsorption efficacy. The beta(1,3)-d-glucan
      and beta(1,6)-d-glucan compositions of the two alkali-extracted fractions and
      their involvement in the adsorption process are discussed.

PMID- 15161248
TI  - Antioxidative and antiglycative effects of six organosulfur compounds in low
      density lipoprotein and plasma.
AB  - Low-density lipoprotein (LDL) and plasma were isolated from patients with non
      insulin-dependent diabetes. The protective effects of six organosulfur compounds
      (DAS, diallyl sulfide; DADS, diallyl disulfide; SAC, S-allylcysteine; SEC, S
      ethylcysteine; SMC, S-methylcysteine; SPC, S-propylcysteine) against further
      oxidation and glycation in these already partially oxidized and glycated samples
      were studied. DAS and DADS showed significantly greater oxidative-delaying
      effects than four cysteine-containing compounds in both partially oxidized LDL
      and plasma samples (P < 0.05). However, cysteine-containing agents were superior
      to DAS and DADS in delaying glycative deterioration in already partially glycated
      LDL (P < 0.05). The observed delays of oxidative and glycative effects from each
      agent were significantly concentration-dependent (P < 0.05). Furthermore, six
      organosulfur agents significantly decreased the loss of catalase and glutathione
      peroxidase activities in plasma and increased alpha-tocopherol retention in LDL
      and plasma (P < 0.05). These results suggested that the use of these organosulfur
      agents derived from garlic at these concentrations could protect partially
      oxidized and glycated LDL or plasma against further oxidative and glycative
      deterioration, which might benefit patients with diabetic-related vascular
      diseases.

PMID- 15161249
TI  - Rewiring cell adhesion.
AB  - The adhesion of cells is mediated by the binding of several cell-surface
      receptors to ligands found in the extracellular matrix. These receptors often
      have overlapping specificities for the peptide ligands, making it difficult to
      understand the roles for discrete receptors in cell adhesion, migration, and
      differentiation as well as to direct the selective adhesion of cell types in
      tissue-engineering applications. To overcome these limitations, we developed a
      strategy to rewire the receptor-ligand interactions between a cell and substrate
      to ensure that adhesion is mediated by a single receptor with unique specificity.
      The strategy combines a genetic approach to engineer the cell surface with a
      chimeric integrin receptor having a unique ligand binding domain with a surface
      chemistry approach to prepare substrates that present ligands that are bound by
      the new binding domain. We show that Chinese hamster ovary cells that are
      engineered with a chimeric beta1 integrin adhere, signal, and even migrate on a
      synthetic matrix.

PMID- 15161250
TI  - Self-assembly of C(3)(h) and C(s) symmetric keto-enamine forms of tris(N-salicyl
      ideneanilines) into columnar phases: a new family of discotic liquid crystals.
AB  - A new class of discotic liquid crystals derived from tris(N-salicylideneanilines)
      existing exclusively in their C3h and Cs keto-enamine tautomeric forms is
      reported. These compounds self-assemble to form columnar liquid crystalline
      phases with a small core-core separation as evidenced by X-ray diffraction
      studies.

PMID- 15161251
TI  - An addressable antibody nanoarray produced on a nanostructured surface.
AB  - The ability to address specific nanoscale features is required to produce diverse
      biological nanoarrays or perform local assembly using biological building blocks
      and is an important unsolved problem in nanotechnology. In this work, we describe
      the use of a novel nanofabricated gold surface, with regions of distinct
      topography and chemical functionalities, to solve this problem. First, nanoarrays
      of IgG antibodies were produced by selective immobilization in nanoholes on the
      surface. The smallest feature size was determined by the hole size (fwhm 90 nm)
      and not surface diffusion. Using holes of 300 nm diameter, we selectively
      addressed specific features in the array by nanopipet delivery of a functional
      antibody, anti-IgG. To our knowledge, this is the first example of addressing
      specific biologically functional features on a surface at the nanoscale.

PMID- 15161252
TI  - Synthesis and characterization of the non-Kekule, singlet biradicaloid
      Ar'Ge(micro-NSiMe(3))(2)GeAr' (Ar' = 2,6-Dipp(2)C(6)H(3), Dipp = 2,6-i
      Pr(2)C(6)H(3)).
AB  - Reaction of Ar'GeGeAr' (1) with an excess of Me3SiN3 gives the non-Kekule,
      biradicaloid Ar'Ge(mu-NSiMe3)2GeAr' (3, Ar' = 2,6-Dipp2C6H3, Dipp = 2,6-i
      Pr2C6H3) which has a planar Ge2N2Si2 array and pyramidal geometry at the
      germaniums. DFT calculations for the model MeGe(mu-NSiH3)2GeMe indicate no Ge-Ge
      bonding and a singlet ground state. The calculated energy difference between the
      optimized singlet and triplet states is 17.51 kcal/mol.

PMID- 15161254
TI  - Multistep energy transfer in single molecular photonic wires.
AB  - We demonstrate the synthesis and spectroscopic characterization of an
      unidirectional photonic wire based on four highly efficient fluorescence energy
      transfer steps (FRET) between five spectrally different chromophores covalently
      attached to double-stranded DNA. The DNA-based modular conception enables the
      introduction of various chromophores at well-defined positions and arbitrary
      interchromophore distances. While ensemble fluorescence measurements show overall
      FRET efficiencies between 15 and 30%, single-molecule spectroscopy performed on
      four spectrally separated detectors easily uncovers subpopulations that exhibit
      overall FRET efficiencies of up to approximately 90% across a distance of 13.6 nm
      and a spectral range of approximately 200 nm. Fluorescence trajectories of
      individual photonic wires show five different fluorescence intensity patterns
      which can be ascribed to successive photobleaching events.

PMID- 15161253
TI  - Creating fluid and air-stable solid supported lipid bilayers.
AB  - Solid supported lipid bilayers are rapidly delaminated when drawn through the
      air/water interface. We have discovered that a close packed monolayer of
      specifically bound protein prevents this process. The protection mechanism worked
      in two ways. First, when protein-protected bilayers were drawn through the
      air/water interface, a thin bulk water layer was visible over the entire bilayer
      region, thereby preventing air from contacting the surface. Second, a stream of
      nitrogen was used to remove all bulk water from a protected bilayer, which
      remained fully intact as determined by fluorescence microscopy. The condition of
      this dried bilayer was further probed by fluorescence recovery after
      photobleaching. It was found that lipids were not two-dimensionally mobile in dry
      air. However, when the bilayer was placed in a humid environment, 91% of the
      bleached fluorescence signal was recovered, indicating long-range two-dimensional
      mobility. The diffusion coefficient of lipids under humid conditions was an order
      of magnitude slower than the same bilayer under water. Protected bilayers could
      be rehydrated after drying, and their characteristic diffusion coefficient was
      reestablished. Insights into the mechanism of bilayer preservation were
      suggested.

PMID- 15161255
TI  - Cavitand-based nanoscale coordination cages.
AB  - This communication reports design, self-assembly, solution, and solid-state
      characterization of nanoscale coordination cages formed by tetradentate cavitand
      ligands and appropriate metal precursors. The preorganization of the cavitand
      ligand in terms of structural rigidity and relative orientation of the pyridyl
      units leads to the exclusive formation of coordination cages in a wide
      temperature and concentration range. Desired features of the cage self-assembly
      process, such as reversibility in the presence of a competitive ligand and self
      recognition of the cavitand components, have been assessed.

PMID- 15161256
TI  - Magic-numbered Au(n) clusters protected by glutathione monolayers (n = 18, 21,
      25, 28, 32, 39): isolation and spectroscopic characterization.
AB  - Small gold clusters (<1 nm) protected by a glutathione (GSH) monolayer were
      fractionated into six components by polyacrylamide gel electrophoresis, and their
      chemical compositions were investigated by electrospray ionization mass
      spectroscopy. The results demonstrate isolation of a series of magic-numbered
      gold clusters, Au18(SG)11, Au21(SG)12, Au25+/-1(SG)14+/-1, Au28(SG)16,
      Au32(SG)18, and Au39(SG)23. Their optical absorption spectra are highly
      structured with clear absorption onsets, which shift toward higher energies with
      reduction of the core size. These molecular-like gold clusters exhibit visible
      photoluminescence. The results reported herein provide helpful guidelines or
      starting points for further experimental and theoretical studies on structures,
      stabilities, and optical properties of monolayer-protected gold clusters.

PMID- 15161257
TI  - A quantum dot conjugated sugar ball and its cellular uptake. On the size effects
      of endocytosis in the subviral region.
AB  - The lipophilic CdSe quantum dot (QD) coated with trioctylphosphine oxide (TOPOQD)
      can be extracted from chloroform into water upon interaction with macrocyclic
      glycocluster amphiphile 1. The QD-conjugated and highly fluorescent sugar ball of
      a size of 15 nm (TOPOQD1) thus solubilized in water readily invades Hela cells
      via endocytosis. The endocytic activity of TOPOQD1 (15 nm), in light of those of
      the micellar homoaggregate of 1 (5 nm) and the virus-like 1-DNA conjugate (50 nm)
      as references, reveals a dramatic size effect (50 > 15 > 5) in the subviral size
      region. The optimal size at approximately 50 nm indicates that size
      complementarity which governs molecular recognition in small host-guest systems
      also plays key roles in the encapsulation of nanometric guest particles by the
      endocytic vesicles (</=100 nm) as a macrobiomolecular host. The work thus
      suggests an utmost importance of size control at the viral size when designing
      molecular (gene, drug, probe, etc.) delivery machines.

PMID- 15161258
TI  - Chalcogens as terminal ligands to iron: synthesis and structure of complexes with
      Fe(III)-S and Fe(III)-Se motifs.
AB  - Metal complexes with terminal chalcogenido ligands are known for the early
      transition-metal complexes, yet for the heavier congeners (e.g., sulfido and
      selenido), there are no analogous examples for the late 3d metal ions. Reported
      herein is the isolation and characterization of monomeric iron(III) complexes
      containing sulfido and selenido ligands; isolation was accomplished using the
      tripodal ligand tris[(N'-tert-butylureaylato)-N-ethylene]aminato ([H3buea]3-).
      The FeIII-E (E = S2-, Se2-) complexes were prepared from the iron(II) precursor,
      [FeII(H3buea)]2-, and the elemental forms of the chalogen. The formulation of
      [FeIIIH3buea(S)]2- and [FeIIIH3buea(Se)]2- as monomeric complexes with Fe-E units
      is supported by spectroscopic, analytical, and X-ray diffraction studies. For
      instance, X-band EPR spectra contain well-resolved axial signals, which are
      consistent with each complex having S = 5/2 ground states. The solid-state
      molecular structures reveal FeIII-E bond lengths of 2.211(1) and 2.355(1) A for
      [FeIIIH3buea(S)]2- and [FeIIIH3buea(Se)]2-, respectively. The primary
      coordination sphere for each complex also contains three deprotonated urea
      nitrogen atoms from [H3buea]3-; the apical amine nitrogen atom weakly interacts
      with the iron centers at distances of greater than 2.6 A. The terminal
      chalcogenido ligands appear to weakly hydrogen-bond with the urea NH groups of
      the [H3buea]3-; however, open H-bond cavities are observed for [FeIIIH3buea(S)]2-
      and [FeIIIH3buea(Se)]2-, which may contribute to their observed long-term
      instability.

PMID- 15161259
TI  - Dynamic helicity inversion by achiral anion stimulus in synthetic labile
      cobalt(II) complex.
AB  - The helical chirality of a Co(II) complex with a chiral tetradentate ligand is
      completely inverted from Lambda to Delta by the addition of achiral NO3- anion as
      an external stimulus.

PMID- 15161260
TI  - Definitive evidence for the contribution of biradical character in a closed-shell
      molecule, derivative of 1,4-bis-(4,5-diphenylimidazol-2-ylidene)cyclohexa-2,5
      diene.
AB  - This study provides conclusive proof that the thermally excited open-shell state
      with biradical character is contributing to the ground state of a closed-shell
      molecule, tF-BDPI-2Y, where four hydrogen atoms at the central phenylene ring are
      substituted with four fluorine atoms of 1,4-bis-(4,5-diphenylimidazol-2
      ylidene)cyclohexa-2,5-diene (BDPI-2Y). A small increase in the population of
      biradical species of tF-BDPI-2Y results in the formation of the dimer form by the
      radical recombination reaction. Controlling the equilibrium between a closed
      shell diamagnetic-quinoid state and an open-shell paramagnetic-biradical state
      will provide significant progress in the field of pi-conjugated delocalized
      biradical chemistry.

PMID- 15161261
TI  - A highly discriminating quencher-free molecular beacon for probing DNA.
AB  - We inserted a fluorene-labeled deoxyuridine derivative, synthesized using
      Sonogashira coupling, efficiently into the loop region of a DNA hairpin using
      phosphoramidite chemistry. This molecular beacon, which features no additional
      fluorescence quencher, discriminates between perfect and one-base-mismatched base
      pairing by changes in its fluorescence intensity. The discrimination factor is
      14.7 for the recognition of a single (A/C) base mismatch.

PMID- 15161262
TI  - Salt-dependent heat capacity changes for RNA duplex formation.
AB  - Two short non-self-complementary RNA duplexes have been probed extensively to
      assess whether the heat capacity change (DeltaCP) for RNA duplex formation is
      sensitive to the solution ionic strength. Isothermal titration calorimetry data
      for duplex formation were collected as a function of temperature to obtain the
      DeltaCP values under each condition. Ionic strength was varied by repeating the
      measurements in the presence of 0.1-1.5 M added NaCl. In both cases, the DeltaCP
      for duplex formation was shown to have a significant dependence on the solution
      ionic strength, varying linearly with the log of the added NaCl. In each case,
      the DeltaCP became more negative at high ionic strength. Heat capacity changes
      have been much better studied in the area of protein folding where DeltaCP is not
      strongly dependent upon ionic strength but instead depends primarily on the
      burial of hydrophobic surface. Whereas hydrophobic burial is almost certainly
      involved in RNA duplex formation as well, the polyanionic nature of the backbone
      and the associated ion condensation effects are almost certainly a contributor to
      the observed ionic strength dependence of DeltaCPs for duplex formation. These
      data also hint at the possibility that nearest neighbor effects may be evident in
      the heat capacity changes associated with nucleic acid folding.

PMID- 15161263
TI  - Electrochemical detection of DNA triplet repeat expansion.
AB  - Hereditary neurodegenerative diseases are connected with the expansion of
      trinucleotide repetitive sequences in genomic DNA. Molecular diagnosis of these
      diseases is based on the determination of the triplet repeat length. Currently
      used methods involve PCR amplification followed by electrophoretic determination
      of the amplicon size. We propose a novel electrochemical technique based on
      hybridization of target DNA (tDNA) immobilized at magnetic beads with a reporter
      probe (RP) complementary to the triplet repeats (12 units per RP). The biotin
      labeled RP is detected via an enzyme-linked electrochemical assay involving
      binding of streptavidin-alkaline phosphatase conjugate and transformation of
      electroinactive 1-naphthyl phosphate to electroactive 1-naphthol. Pyrimidine
      residues within sequences flanking the homopurine (GAA)n repeat in tDNA are
      premodified with osmium tetroxide, 2,2'-bipyridine (Os,bipy), introducing
      electroactive labels in tDNA. The length of the triplet expansion is calculated
      from the ratio of the intensities of electrochemical signals of hybridized
      RP/tDNA-Os,bipy. The normalized signal increases linearly with the repeat length
      between 0 and about 200 triplet units, allowing for discrimination between
      normal, premutated, and mutated alleles. Application of this method for the
      detection of the asymptomatic heterozygous carrier of expanded alleles is
      demonstrated.

PMID- 15161264
TI  - Characterization of the glycosyltransferase activity of desVII: analysis of and
      implications for the biosynthesis of macrolide antibiotics.
AB  - In vitro catalytic activity of DesVII, the glycosyltransferase involved in the
      biosynthesis of methymycin, neomethymycin, narbomycin, and pikromycin in
      Streptomyces venezuelae, is described. This is the first report of demonstrated
      in vitro activity of a glycosyltransferase involved in the biosynthesis of
      macrolide antibiotics. DesVII is unique among glycosyltransferases in that it
      requires an additional protein component, DesVIII, as well as basic pH for its
      full activity.

PMID- 15161266
TI  - Catalytic asymmetric vinylation of ketones.
AB  - This communication describes the catalytic asymmetric 1,2-addition of vinylzinc
      reagents to aromatic, alpha,beta-unsaturated, and dialkyl ketones with
      enantioselectivities between 79 and 97% and with yields ranging from 84 to 98%.
      The products of these reactions are tertiary allylic alcohols with chiral
      quaternary centers that are useful in organic synthesis. The reaction involves
      hydrozirconation of a terminal alkyne, transmetalation to zinc, and addition to a
      ketone in the presence of a chiral titanium-based Lewis acid catalyst. The
      reactions proceed smoothly at room temperature in under 24 h.

PMID- 15161265
TI  - Identification of nuclear proteins that interact with platinum-modified DNA by
      photoaffinity labeling.
AB  - Interactions between cellular proteins and cisplatin-modified DNA are important
      in determining the anticancer activity of the drug. To develop a general approach
      for identifying proteins that mediate cellular responses to cisplatin,
      photoreactive cisplatin analogues having a tethered benzophenone moiety were
      prepared and used to form the major 1,2-intrastrand platinum-DNA cross-links.
      Upon irradiation of the platinated DNA dissolved in a HeLa nuclear extract, the
      appended photolabile benzophenone group generates a highly reactive species that
      binds irreversibly to cellular proteins that interact with the probe. Several DNA
      protein cross-linked adducts were identified that may function in the cellular
      processing of cisplatin-DNA adducts. Of these, PARP-1 had not previously been
      demonstrated directly to contact Pt-DNA cross-links in human cells.

PMID- 15161268
TI  - Bimetallic catalysis for styrene homopolymerization and ethylene-styrene
      copolymerization. Exceptional comonomer selectivity and insertion regiochemistry.
AB  - This communication reports the styrene homopolymerization behavior and ethylene
      styrene copolymerization behavior of the covalently linked bimetallic constrained
      geometry catalyst (mu-CH2CH2-3,3'){(eta5-indenyl)[1-Me2Si(tBuN)](TiMe2)}2 (Ti2),
      which is the first single-site catalyst that effects not only styrene
      homopolymerization with high activity, but also efficient ethylene-styrene
      copolymerization over a broad styrene composition range (0-76% at 20 degrees C,
      1.0 atm ethylene pressure). In styrene homopolymerization, a 50x increase in
      polymerization activity is achieved with Ti2 vs the mononuclear analogue, Ti1,
      using an identical trityl borate cocatalyst and polymerization conditions. In
      ethylene + styrene copolymerization, Ti2 enchains approximately 20% more styrene
      than Ti1 under identical reaction conditions. 13C NMR spectroscopy indicates that
      greater than two consecutive styrene units are enchained in the copolymer
      backbone produced by Ti2 + Ph3C+B(C6F5)4-. End group analysis of the styrene
      homopolymer produced by Ti2 + Ph3C+B(C6F5)4- suggests that 1,2-regiochemistry is
      installed in approximately 50% of the initiation steps. This unusual
      microstructure is believed to be related to the bimetallic catalyst structure.

PMID- 15161267
TI  - Electron conduction across electrode-immobilized neutravidin bound with biotin
      labeled ruthenium pentaamine.
AB  - Voltammetry is reported here of a self-assembled redox-protein conjugate
      consisting of neutravidin conjugated with a biotin derivative redox probe,
      Ru(NH3)5(N-[(N-[(4-pyridyl)methyl]biotinamide], immobilized on gold electrodes
      modified by self-assembled monolayers of mercaptoundecanoic acid. This
      voltammetry indicates that self-assembly of the conjugate/electrode electronic
      interface, driven by electrostatic binding between the monolayer and a single
      redox probe, favors orientation of the conjugate, resulting in electronic
      accessibility of the remaining three redox probes.

PMID- 15161269
TI  - Importance of intermolecular interactions in assessing hopping mobilities in
      organic field effect transistors: pentacene versus dithiophene
      tetrathiafulvalene.
AB  - We report on a computational study to understand the high mobility found in
      dithiophene-tetrathiafulvalene (DT-TTF) transistors, with respect to that known
      for pentacene, using an extended measure of the reorganization energy
      (lambdareorg). We demonstrate the high importance of considering intermolecular
      interactions to assess hole-hopping mobilities. We find that due to the steric,
      polarizable environment and the structural changes induced by local
      intermolecular charge delocalization, the calculated lambdareorg for DT-TTF
      decreases from 0.574 eV in the isolated molecule to 0.042 eV in the crystal
      embedded molecule, which is of the same order of the previously reported value
      found for the isolated pentacene molecule, 0.098 eV.

PMID- 15161270
TI  - Experimental resolution of early steps in protein folding: testing molecular
      dynamics simulations.
AB  - Time-resolved Tyr fluorescence spectroscopy coupled with a laser-induced
      temperature-jump (T-jump) was employed to follow the folding relaxation dynamics
      of the B-domain of Staphylococcal protein A. The single Tyr is located in helix 1
      (H1) and is a sensitive probe of the structure of this helix and the overall
      helical bundle structure. The results from this study were compared to those from
      a complementary infrared T-jump study on this protein [Vu, D. M.; Myers, J. K.;
      Oas, T. G.; Dyer, R. B. Biochemistry 2004, 43, 3582]. Both methods detect a
      microsecond process that follows the cooperative relaxation of the helical bundle
      core. However, a fast process (10-7 s) that follows the relaxation of the
      individual helices was observed only with the infrared probe. Thus, fast
      formation of H1 is not observed, but rather H1 forms in the microsecond phase,
      concomitantly with the docking to (and stabilization by) the other two helices to
      form the helical bundle structure. This observation validates the results of
      several previous molecular dynamics simulations that predict H1 formation only in
      the final assembly of the helix bundle.

PMID- 15161271
TI  - Oxidation of 5-hydroxy-2'-deoxyuridine into isodialuric acid, dialuric acid, and
      hydantoin products.
AB  - Oxidation products of cytosine, including 5-hydroxycytosine and 5-hydroxyuracil,
      are highly susceptible to subsequent oxidation. Here, the oxidation products of 5
      hydroxy-2'-deoxyuridine have been studied by NMR and MS analyses. The initial
      products were diastereomers of isodialuric acid nucleoside. These products
      subsequently decomposed into corresponding dialuric acid derivatives at neutral
      pH. The position of the carbonyl and hydroxyl groups, at C5 and C6 for
      isodialuric acid and at C6 and C5 for dialuric acid derivatives, respectively,
      was determined by 1H- and 13C NMR analyses. In addition, these analyses revealed
      that the carbonyl groups of both isodaluric and dialuric acid derivatives exist
      in their fully hydrated form in aqueous solution. Finally, the dialuric acid
      derivatives were observed to undergo subsequent decomposition into the
      corresponding 5-hydroxyhydantoin derivatives. Studies of a trinucleotide
      containing 5-hydroxyuracil suggest that the reactions described herein for the
      monomer can be extrapolated to DNA.

PMID- 15161272
TI  - Employing end-functional polythiophene to control the morphology of nanocrystal
      polymer composites in hybrid solar cells.
AB  - A poly(3-hexylthiophene) containing an interacting amino chain end enhances the
      performance of P3HT/CdSe solar cells by increasing the dispersion of CdSe
      nanocrystals and improving the morphology of the nanocomposite without
      introducing insulating surfactants.

PMID- 15161273
TI  - Facile formation of an intrastrand cross-link lesion between cytosine and guanine
      upon pyrex-filtered UV light irradiation of d((Br)CG) and duplex DNA containing 5
      bromocytosine.
AB  - Pyrex-filtered UV light irradiation of d(BrCG) and 5-bromocytosine-containing
      duplex DNA leads to facile formation of a cross-link lesion between the C5 carbon
      atom of cytosine and the C8 carbon atom of its adjacent guanine. A similar cross
      link lesion has been previously found in the X-ray irradiation mixture of
      d(CGTA).

PMID- 15161274
TI  - Homogeneous palladium catalyst suppressing Pd black formation in air oxidation of
      alcohols.
AB  - In homogeneous catalyst systems, there is the persistent problem that metal
      aggregation and precipitation cause catalyst decomposition and considerable loss
      of catalytic activity. Pd black formation is a typical example. Pd catalysts are
      known to easily aggregate and form Pd black, although they realize a wide variety
      of useful reactions in organic synthesis. In order to overcome this intrinsic
      problem of homogeneous Pd catalysis, we explored a new class of Pd catalyst by
      adopting aerobic oxidation of alcohols as a probe reaction. Herein we report a
      new catalyst system that suppresses the Pd black formation even under air and
      with a high substrate to catalyst molar ratio (S/C: more than 1000) in oxidation
      of alcohols. The novel pyridine derivatives having a 2,3,4,5-tetraphenylphenyl
      substituent and its higher dendritic unit at the 3-position of the pyridine ring
      were found to be excellent ligands with Pd(OAc)2 in the palladium-catalyzed air
      (balloon) oxidation of alcohols in toluene at 80 degrees C. Comparison with
      structurally related pyridine ligands revealed that introduction of the 2,3,4,5
      tetraphenylphenyl substituent at the 3-position of pyridine ring effectively
      suppresses the Pd black formation, maintaining the catalytic activity for a long
      time to give aldehydes or ketones as products in high yields.

PMID- 15161275
TI  - Cross-coupling of sp(3) C-H bonds and alkenes: catalytic cyclization of alkene
      amide substrates.
AB  - We herein present a new oxidative cyclization of alkene-amide substrates under
      neutral and catalytic conditions. This overall transformation requires tandem sp3
      C-H activation (at the position adjacent to the amide nitrogen) and C-C bond
      formation. Specifically, pyrrolidine 1 was converted to pyrrolizidinone 3 and
      indolizidinone 4 in 66% and 17% yield, respectively, in the presence of
      [Ir(coe)2Cl]2, the carbene ligand IPr (1:1 metal/ligand ratio, 5-10 mol % of Ir),
      and the hydrogen acceptor (NBE or TBE, 3-10 equiv). The results presented in this
      study suggest that complex 10 [IPr-Ir(Cl)(substrate)] is the key intermediate in
      the catalytic cycle. On the mechanistic front, the key advance was the ability to
      facilitate C-H activation and alkene insertion in tandem, and in preference to
      beta-hydride elimination, in the context of amide substrates. With respect to
      complex synthesis, catalytic and neutral conditions of this method unlock new
      exciting opportunities as illustrated by regioselective cyclization of the
      proline-derived substrate 16.

PMID- 15161276
TI  - Catalytic asymmetric synthesis of alpha-amino phosphonates using enantioselective
      carbon-carbon bond-forming reactions.
AB  - We have developed highly enantioselelctive reactions of silicon enolates with N
      acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates.
      A copper (II)-diamine complex was shown to be effective in this reaction, and
      high levels of yield and selectivity were achieved. It is noteworthy that this
      reaction opens a way to various biologically important, optically active alpha
      amino phosphonate derivatives.

PMID- 15161277
TI  - Mixed-metal metallocryptands. Short metal-metal separations strengthened by a
      dipolar interaction.
AB  - The deep-red, air-stable mixed-metal metallocryptands, [AuPdTl(P2phen)3](PF6)2,
      1.(PF6)2, and [AuPtTl(P2phen)3](PF6)2, 2.(PF6)2, are easily prepared in good
      yield (60-70%) by reacting 3 equiv of P2phen with 1 equiv of Au(THT)Cl, excess
      thallous acetate, and the appropriate amount of either Pd2(dba)3 for 1 or
      Pt(dba)2 for 2 in acetonitrile where P2phen is 2,9-bis(diphenylphosphino)-1,10
      phenanthroline, THT is tetrahydrothiophene, and dba is dibenzylidineacetone.
      Compared to the more symmetrical bimetallic metallocryptands, these trimetallic
      species show shorter than expected Au(I)-Tl(I), Pt(0)-Tl(I), and Pd(0)-Tl(I)
      separations. The enhanced bonding interaction is attributed to the incorporation
      of the dissimilar capping metals introducing dipole moments that strengthen the
      dispersion forces responsible for maintaining the metallophilic interactions.

PMID- 15161278
TI  - Two-stage dispersion polymerization toward monodisperse, controlled micrometer
      sized copolymer particles.
AB  - We describe a two-stage dispersion polymerization process to prepare monodisperse
      micrometer-sized polymer particles in which problematic reagents, such as
      functional monomers and cross-linkers that commonly disrupt the particle-forming
      process, were added to the reaction after the nucleation stage was complete.
      Comonomers added after this point became incorporated into the particles without
      disturbing the final particle size and size distribution. In this way dye-labeled
      or functional group-containing micrometer-sized particles with a very narrow size
      distribution were prepared. By varying the amount of monomer added in the second
      stage, the final particle diameter could be controlled precisely. Most important
      of all, this synthetic strategy allowed us to prepare cross-linked particles
      containing up to 3 mol % cross-linking agent.

PMID- 15161279
TI  - Intramolecular reductive nitrosylation: reaction of nitric oxide and a copper(II)
      complex of a cyclam derivative with pendant luminescent chromophores.
AB  - The base-catalyzed reaction of nitric oxide with the Cu(II) complex Cu(DAC)2+
      (DAC = 1,8-bis(9-anthracyl-methyl)-(1,4,8,11-tetraazacyclotetradecane)) leads to
      reduction of the metal center and the unexpected intramolecular nitrosylation of
      a secondary amine.

PMID- 15161281
TI  - Enantiodifferentiating photoaddition of alcohols to 1,1-diphenylpropene in
      supercritical carbon dioxide: sudden jump of optical yield at the critical
      density.
AB  - In the enantiodifferentiating photoaddition of ROH (R = Me, Et, i-Pr) to 1,1
      diphenylpropene sensitized by fructosyl 1,4-naphthalenedicarboxylate in
      supercritical carbon dioxide, the enantiomeric excess of photoadduct increased
      with increasing bulkiness of the alcohol at all pressures used, with an
      accompanying sudden jump at the critical density, for which the enhanced
      clustering of alcohol, particularly in the subcritical pressure region, was
      revealed to be responsible from the fluorescence spectral examinations.

PMID- 15161280
TI  - (P)-helicene displays chiral selection in binding to Z-DNA.
AB  - Enantiomeric helicenes of (P)-A and (M)-A were synthesized. The binding of the
      helicenes to B- and Z-DNA was studied quantitatively by CD, equilibrium dialysis,
      and fluorescence spectroscopy. Enantiomeric (P)-A not only bound selectively to Z
      DNA but also effectively converted the B-DNA conformation to Z-DNA. The
      enantioselectivity of the helicenes offers a new route for the rational design of
      inhibitors of biological functions that may depend on Z-DNA.

PMID- 15161282
TI  - Selective extraction of higher fullerenes using cyclic dimers of zinc porphyrins.
AB  - Higher fullerenes (>/=C76) were selectively extracted from a fullerene mixture
      obtained from a combustion-based industrial production source by cyclic dimers of
      beta-unsubstituted porphyrin zinc complexes 2C5-2C7 with C5-C7 alkylene spacers
      as host molecules. Results of single extraction of the fullerene mixture with 2C5
      2C7 together with a beta-substituted analogue of 2C6 (1C6) and spectroscopic
      titration of 2C6 and 1C6 with C60, C70, and C96 indicated that the host
      selectivity toward higher fullerenes is much dependent on the structure of the
      porphyrin units and the size of the host cavity. Sequential three-stage
      extraction of the fullerene mixture with the best-behaved 2C6 resulted in
      considerable enrichment in very rare fullerenes C102-C110 (<0.1 abs %) up to 82
      abs % (C76-C114, 99 abs %) (356 nm) of total fullerenes.

PMID- 15161283
TI  - In situ gamma ray-initiated polymerization to stabilize surface micelles.
AB  - Surfactant molecules containing hydrophobic long alkyl chains and hydrophilic
      groups can organize into various micellar structures both in bulk solution and at
      interface. However, because of the dynamical nature of surfactant micelles,
      efforts directed at fixing their structures in bulk solution by polymerization
      have met with limited success. Herein, we report a unique and simple method of
      stabilizing surface micelles of a low molecular weight surfactant 11
      acryloyloxyundecyltriethylammonium bromide (AUTEAB) through in situ intramicellar
      polymerization on the mica surface. Atomic force microscopy (AFM) observations
      show that the cylindrical micellar structure formed by AUTEAB monomers at the
      mica/water interface is preserved after the in situ polymerization, and the
      stability of the polymerized surface micelles is greatly enhanced compared with
      that of the unpolymerized ones.

PMID- 15161284
TI  - High-frequency and -field EPR of a pseudo-octahedral complex of high-spin Fe(II):
      bis(2,2'-bi-2-thiazoline)bis(isothiocyanato)iron(II).
AB  - A pseudo-octahedral complex of high-spin Fe(II), bis(2,2'-bi-2
      thiazoline)bis(isothiocyanato)iron(II), which has a cis-FeN'2N4 chromophore, has
      been investigated by high-frequency, high-field electron paramagnetic resonance
      (HFEPR). Complementary Mossbauer and DC magnetic susceptibility studies were also
      performed. HFEPR spectra of powder samples were recorded at frequencies up to 700
      GHz and over a magnetic field range of 0-25 T. Analysis of the field-frequency
      data set yields the following set of spin Hamiltonian parameters for S = 2: D =
      +12.427(12) cm-1, E = +0.243(3) cm-1; gx = 2.147(3), gy = 2.166(3), gz = 2.01(1).
      The parameters are analyzed by use of a simple crystal-field model. This study
      represents the first precise determination by HFEPR of spin Hamiltonian
      parameters in six-coordinate high-spin Fe(II) and indicates the applicability of
      HFEPR to the study of high-spin Fe(II) in coordination complexes and biological
      model compounds.

PMID- 15161285
TI  - Toward fully synthetic glycoproteins by ultimately convergent routes: a solution
      to a long-standing problem.
AB  - A method is disclosed for the convergent synthesis of multiply glycosylated
      peptides. The approach centers on a convergent technique for generating masked,
      complex glycopeptide-containing C-terminal acyl donors. Activation of the latent
      donor in situ and use directly in segment coupling with a second peptide bearing
      a complex carbohydrate produces a completely unprotected, bifunctional
      glycopeptide. The system demonstrates a minimum level of hydrolysis and
      epimerization at the C-terminal amino acid residue of the acyl donor during fully
      convergent segment coupling and is therefore a powerful tool for the synthesis of
      glycoproteins.

PMID- 15161287
TI  - A controlled supramolecular approach toward cation-specific chemosensors:
      alkaline earth metal ion-driven exciton signaling in squaraine tethered podands.
AB  - Three different squaraine tethered bichromophoric podands 3a-c with one, two, and
      three oxygen atoms in the podand chain and an analogous monochromophore 4a were
      synthesized and characterized. Among these, the bichromophores 3a-c showed high
      selectivity toward alkaline earth metal cations, particularly to Mg(2+) and
      Ca(2+) ions, whereas they were optically silent toward alkali metal ions. From
      the absorption and emission changes as well as from the Job plots, it is
      established that Mg(2+) ions form 1:1 folded complexes with 3a and 3b whereas
      Ca(2+) ions prefer to form 1:2 sandwich dimers. However, 3c invariably forms weak
      1:1 complexes with Mg(2+), Ca(2+), and Sr(2+) ions. The signal output in all of
      these cases was achieved by the formation of a sharp blue-shifted absorption and
      strong quenching of the emission of 3a-c. The signal transduction is achieved by
      the exciton interaction of the face-to-face stacked squaraine chromophores of the
      cation complex, which is a novel approach of specific cation sensing. The
      observed cation-induced changes in the optical properties are analogous to those
      of the "H" aggregates of squaraine dyes. Interestingly, a monochromophore 4a
      despite its binding, as evident from (1)H NMR studies, remained optically silent
      toward Mg(2+) and Ca(2+) ions. While the behavior of 4a toward Mg(2+) ion is
      understood, its optical silence toward Ca(2+) ion is rationalized to the
      preferential formation of a "Head-Tail-Tail-Head" arrangement in which exciton
      coupling is not possible. The present study is different from other known reports
      on chemosensors in the sense that cation-specific supramolecular host-guest
      complexation has been exploited for controlling chromophore interaction via
      cation-steered exciton coupling as the mode of signaling.

PMID- 15161286
TI  - Ferrous binding to the multicopper oxidases Saccharomyces cerevisiae Fet3p and
      human ceruloplasmin: contributions to ferroxidase activity.
AB  - The multicopper oxidases are a family of enzymes that couple the reduction of
      O(2) to H(2)O with the oxidation of a range of substrates. Saccharomyces
      cerevisiae Fet3p and human ceruloplasmin (hCp) are members of this family that
      exhibit ferroxidase activity. Their high specificity for Fe(II) has been
      attributed to the existence of a binding site for iron. In this study, mutations
      at the E185 and Y354 residues, which are putative ligands for iron in Fet3p, have
      been generated and characterized. The effects of these mutations on the
      electronic structure of the T1 Cu site have been assessed, and the reactivities
      of this site toward 1,4-hydroquinone (a weak binding substrate) and Fe(II) have
      been evaluated and interpreted in terms of the semiclassical Marcus theory for
      electron transfer. The electronic and geometric structure of the Fe(II) substrate
      bound to Fet3p and hCp has been studied for the first time, using variable
      temperature variable field magnetic circular dichroism (VTVH MCD) spectroscopy.
      The iron binding sites in Fet3p and hCp appear to be very similar in nature, and
      their contributions to the ferroxidase activity of these proteins have been
      analyzed. It is found that these iron binding sites play a major role in tuning
      the reduction potential of iron to provide a large driving force for the
      ferroxidase reaction, while still supporting the delivery of the Fe(III) product
      to the acceptor protein. Finally, the analysis of possible electron-transfer (ET)
      pathways from the protein-bound Fe(II) to the T1 Cu site indicates that the E185
      residue not only plays a role in iron binding, but also provides the dominant ET
      pathway to the T1 Cu site.

PMID- 15161289
TI  - Organic spin clusters: macrocyclic-macrocyclic polyarylmethyl polyradicals with
      very high spin S = 5-13.
AB  - Synthesis and magnetic studies of a new class of organic spin clusters,
      possessing alternating connectivity of unequal spins, are described.
      Polyarylmethyl polyether precursors to the spin clusters, with linear and
      branched connectivity between calix[4]arene-based macrocycles, are prepared via
      modular, multistep syntheses. Their molecular connectivity and stereoisomerism
      are analyzed using NMR spectroscopy. The absolute masses (4-10 kDa) are
      determined by FABMS and GPC/MALS. Small angle neutron scattering (SANS) provides
      the radii of gyration of 1.2-1.8 nm. The corresponding polyradicals with 15, 22,
      and 36 triarylmethyls, which are prepared and studied as solutions in
      tetrahydrofuran-d(8), may be described as S' = 7/2, 1/2, 7/2 spin trimer (average
      S = 5-6), S' = 7/2, 1/2, 6/2, 1/2, 7/2 spin pentamer (average S = 7-9), and spin
      nonamer (average S = 11-13), respectively, as determined by SQUID magnetometry
      and numerical fits to linear combinations of the Brillouin functions. For spin
      trimer and pentamer, the quantitative magnetization data are fit to new
      percolation models, based upon random distributions of chemical defects and
      ferromagnetic vs antiferromagnetic couplings. The value of S = 13 is the highest
      for an organic molecule.

PMID- 15161290
TI  - Divalent binding of a bis(adamantyl)-functionalized calix[4]arene to beta
      cyclodextrin-based hosts: an experimental and theoretical study on multivalent
      binding in solution and at self-assembled monolayers.
AB  - The divalent binding of a bis(adamantyl)-functionalized calix[4]arene (1) to an
      EDTA-tethered beta-cyclodextrin (CD) dimer (2) in solution (1.2 x 10(7) M(-)(1))
      was 3 orders of magnitude weaker than the binding constant ( approximately 10(10)
      M(-)(1)) for the interaction of 1 at CD self-assembled monolayers (SAMs) on gold.
      This difference in binding is rationalized using a theoretical model, which
      interprets the divalent binding as two consecutive monovalent binding events,
      i.e., an intermolecular interaction followed by an intramolecular binding event,
      the latter of which is associated with an effective concentration term accounting
      for the close proximity of the two interacting species. The methodology presented
      in the model is applicable to divalent binding both in solution and at SAMs and
      indicates that the difference in observed binding constants mainly stems from a
      difference in effective concentration.

PMID- 15161288
TI  - Determination of the bioavailability of biotin conjugated onto shell cross-linked
      (SCK) nanoparticles.
AB  - Shell cross-linked nanoparticles (SCKs) presenting surface- and bioavailable
      biotin functional groups were synthesized via a mixed micelle methodology,
      whereby co-micellization of chain terminal biotinylated poly(acrylic acid)-b
      poly(methyl acrylate) (PAA-b-PMA) and nonbiotinylated PAA-b-PMA were cross-linked
      in an intramicellar fashion within the shell layer of the mixed micelles, between
      the carboxylic acid groups of PAA and the amine functionalities of 2,2'
      (ethylenedioxy)diethylamine. The hydrodynamic diameters (D(h)) of the micelles
      and the SCKs with different biotinylated block copolymer contents were determined
      by dynamic light scattering (DLS), and the dimensions of the SCKs were
      characterized with tapping-mode atomic force microscopy (AFM) and transmission
      electron microscopy (TEM). The amount of surface-available biotin was tuned by
      varying the stoichiometric ratio of the biotinylated PAA-b-PMA versus the
      nonbiotinylated PAA-b-PMA, as demonstrated with solution-state, binding
      interaction analyses, an avidin/HABA (avidin/4'-hydroxyazobenzene-2-carboxylic
      acid) competitive binding assay, and fluorescence correlation spectroscopy (FCS).
      The avidin/HABA assay found the amount of available biotin at the surface of the
      biotinylated SCK nanoparticles to increase with increasing biotin-terminated
      block copolymer incorporation, but to be less than 25% of the theoretical value.
      FCS measurements showed the same trend.

PMID- 15161291
TI  - Dynamic devices. Shape switching and substrate binding in ion-controlled
      nanomechanical molecular tweezers.
AB  - As examples of supramolecular devices performing chemical (ionic, molecular)
      control of binding events and models of related natural systems, two molecular
      conformational switches are described, which display cation-controlled
      nanomechanical motion coupled to substrate binding and release. The substrate
      binding relies on donor/acceptor interactions, provided by intercalation between
      planar sites located at the extremities of the switching units, whereas cation
      complexation is responsible for conformational regulation. The terpyridine py-py
      py-based receptor is activated toward substrate binding upon complexation of a
      zinc(II) cation and operates in a two-state process. The replacement of the
      central pyridine by a 4,6-disubstituted pyridimine as in py-pym-py induces a
      state reversal and yields a new receptor which binds a substrate in the absence
      of cation, and releases it when copper(I) is introduced, following a three-step
      process. These systems represent effector-triggered supramolecular switching
      devices leading toward multistate nanomechanical chemical systems. These two
      systems illustrate the use of simple conformational switches in the binding site
      and allosteric regulation of substrate affinity.

PMID- 15161292
TI  - Self-assembly of irregular graphs whose edges are DNA helix axes.
AB  - A variety of computational models have been introduced recently that are based on
      the properties of DNA. In particular, branched junction molecules and graphlike
      DNA structures have been proposed as computational devices, although such models
      have yet to be confirmed experimentally. DNA branched junction molecules have
      been used previously to form graph-like three-dimensional DNA structures, such as
      a cube and a truncated octahedron, but these DNA constructs represent regular
      graphs, where the connectivities of all of the vertexes are the same. Here, we
      demonstrate the construction of an irregular DNA graph structure by a single step
      of self-assembly. A graph made of five vertexes and eight edges was chosen for
      this experiment. DNA branched junction molecules represent the vertexes, and
      duplex molecules represent the edges; in contrast to previous work, specific edge
      molecules are included as components. We demonstrate that the product is a closed
      cyclic single-stranded molecule that corresponds to a double cover of the graph
      and that the DNA double helix axes represent the designed graph. The correct
      assembly of the target molecule has been demonstrated unambiguously by
      restriction analysis.

PMID- 15161293
TI  - Homologous series of dendronized polymethacrylates with a methyleneoxycarbonyl
      spacer between the backbone and dendritic side chain: synthesis,
      characterization, and some bulk properties.
AB  - First through fourth generation (G1-G4) dendronized macromonomers, 3, 5, 7, and
      9, with a methyleneoxycarbonyl spacer between the polymerizable group and
      dendritic side chain (dendron) were synthesized, and their polymerization
      behavior to the corresponding dendronized polymers PG1s, PG2s, PG3s, and PG4s,
      respectively, was investigated by heating the monomers to 55 degrees C without
      intentional addition of initiator. This self-induced polymerization is referred
      to as thermally induced radical polymerization (TRP). The molar masses of PG1s
      PG4s were determined by gel permeation chromatography in DMF calibrated to a
      recently developed G1 dendronized polymer standard (PG1). A comparison of this
      homologous series' polymerization results with those of an already existing one,
      which differed only by the lack of this spacer (referred to as PG1-PG4), was made
      to contribute to the issue of whether short spacers have an effect on
      polymerization. Several representatives of both series were also used in the
      first systematic and generation-dependent investigation of these unusual comb
      polymers' bulk properties. Both structure and dynamics were investigated by DSC,
      X-ray diffraction, and dynamic mechanical measurements.

PMID- 15161294
TI  - Synthesis of atomically ordered AuCu and AuCu(3) nanocrystals from bimetallic
      nanoparticle precursors.
AB  - A new multistep approach was developed to synthesize atomically ordered
      intermetallic nanocrystals, using AuCu and AuCu(3) as model systems. Bimetallic
      nanoparticle aggregates are used as precursors to atomically ordered
      nanocrystals, both to precisely define the stoichiometry of the final product and
      to ensure that atomic-scale diffusion distances lower the reaction temperatures
      to prevent sintering. In a typical synthesis, PVP-stabilized Au-Cu nanoparticle
      aggregates synthesized by borohydride reduction are collected by centrifugation
      and annealed in powder form. At temperatures below 175 degrees C, diffusion of Cu
      into Au occurs, and the atomically disordered solid solution Cu(x)Au(1)(-)(x)
      exists. For AuCu, nucleation occurs by 200 degrees C, and atomically ordered AuCu
      exists between 200 and 400 degrees C. For AuCu(3), an AuCu intermediate nucleates
      at 200 degrees C, and further diffusion of Cu into the AuCu intermediate at 300
      degrees C nucleates AuCu(3). Atomically ordered AuCu and AuCu(3) nanocrystals can
      be redispersed as discrete colloids in solution after annealing between 200 and
      300 degrees C.

PMID- 15161295
TI  - Kinetic and mechanistic investigations of hydrothermal transformations in zinc
      phosphates.
AB  - The room-temperature crystallization of
      [C(6)N(2)H(18)][Zn(HPO(4))(H(2)PO(4))(2)], an organically templated zinc
      phosphate containing [Zn(2)(HPO(4))(2)(H(2)PO(4))(4)](4)(-) molecular anions, and
      its transformation to compounds containing either one- or two-dimensional
      inorganic components, [C(6)N(2)H(18)][Zn(3)(H(2)O)(4)(HPO(4))(4)],
      [C(4)N(2)H(12)][Zn(HPO(4))(2)(H(2)O)], or [C(3)N(2)H(6)][Zn(4)(OH)(PO(4))(3)],
      under hydrothermal conditions were studied in-situ using energy-dispersive X-ray
      diffraction. The ability to collect data during reactions in a large volume (
      approximately 23 mL) Teflon-lined autoclave under real laboratory conditions has
      allowed for the elucidation of kinetic and mechanistic information. Kinetic data
      have been determined by monitoring changes in the integrated peak intensities of
      Bragg reflections and have been modeled using the Avrami-Erofe'ev expression. The
      crystallization of [C(6)N(2)H(18)][Zn(HPO(4))(H(2)PO(4))(2)] is a diffusion
      controlled process, while nucleation is increasingly more important in
      determining the overall rate of the formation of
      [C(6)N(2)H(18)][Zn(3)(H(2)O)(4)(HPO(4))(4)],
      [C(4)N(2)H(12)][Zn(HPO(4))(2)(H(2)O)], and [C(3)N(2)H(6)][Zn(4)(OH)(PO(4))(3)].
      The transformation of [C(6)N(2)H(18)][Zn(HPO(4))(H(2)PO(4))(2)] to
      [C(4)N(2)H(12)][Zn(HPO(4))(2)(H(2)O)] and [C(3)N(2)H(6)][Zn(4)(OH)(PO(4))(3)]
      occurs via a dissolution-reprecipitation mechanism, while the transformation to
      [C(6)N(2)H(18)][Zn(3)(H(2)O)(4)(HPO(4))(4)] may be the first observation of a
      direct topochemical conversion of one organically templated solid to another
      under hydrothermal conditions.

PMID- 15161296
TI  - Activation of the sulfhydryl group by Mo centers: kinetics of reaction of benzyl
      radical with a binuclear Mo(micro-SH)Mo complex and with arene and alkane thiols.
AB  - This paper provides evidence from kinetic experiments and electronic structure
      calculations of a significantly reduced S-H bond strength in the Mo(micro-SH)Mo
      function in the homogeneous catalyst model, CpMo(micro-S)(2)(micro-SH)(2)MoCp (1,
      Cp = eta(5)-cyclopentadienyl). The reactivity of 1 was explored by determination
      of a rate expression for hydrogen atom abstraction by benzyl radical from 1
      (log(k(abs)/M(-)(1) s(-)(1)) = (9.07 +/- 0.38) - (3.62 +/- 0.58)/theta) for
      comparison with expressions for CH(3)(CH(2))(7)SH, log(k(abs)/M(-)(1) s(-)(1)) =
      (7.88 +/- 0.35) - (4.64 +/- 0.54)/theta, and for 2-mercaptonaphthalene,
      log(k(abs)/M(-)(1) s(-)(1)) = (8.21 +/- 0.17) - (4.24 +/- 0.26)/theta (theta =
      2.303RT kcal/mol, 2sigma error). The rate constant for hydrogen atom abstraction
      at 298 K by benzyl radical from 1 is 2 orders of magnitude greater than that from
      1-octanethiol, resulting from the predicted (DFT) S-H bond strength of 1 of 73
      kcal/mol. The radical CpMo(micro-S)(3)(micro-SH)MoCp, 2, is revealed, from the
      properties of slow self-reaction, and exclusive cross-combination with reactive
      benzyl radical, to be a persistent free radical.

PMID- 15161297
TI  - Cyclic perfluorocarbon radicals and anions having high global warming potentials
      (GWPs): structures, electron affinities, and vibrational frequencies.
AB  - Adiabatic electron affinities, optimized molecular geometries, and IR-active
      vibrational frequencies have been predicted for small cyclic hydrocarbon radicals
      C(n)H(2)(n)(-)(1) (n = 3-6) and their perfluoro counterparts C(n)F(2)(n)(-)(1) (n
      = 3-6). Total energies and optimized geometries of the radicals and corresponding
      anions have been obtained using carefully calibrated (Chem. Rev. 2002, 102, 231)
      density functional methods, namely, the B3LYP, BLYP, and BP86 functionals in
      conjunction with the DZP++ basis set. The predicted electron affinities show that
      only the cyclopropyl radical tends to bind electrons among the hydrocarbon
      radicals studied. The trend for the perfluorocarbon (PFC) radicals is quite
      different. The electron affinities increase with expanding ring size until n = 5
      and then slightly decrease at n = 6. Predicted electron affinities of the
      hydrocarbon radicals using the B3LYP hybrid functional are 0.24 eV
      (C(3)H(5)/C(3)H(5)(-)), -0.19 eV (C(4)H(7)/C(4)H(7)(-)), -0.15 eV
      (C(5)H(9)/C(5)H(9)(-)), and -0.11 eV (C(6)H(11)/C(6)H(11)(-)). Analogous electron
      affinities of the perflurocarbon radicals are 2.81 eV (C(3)F(5)/C(3)F(5)(-)),
      3.18 eV (C(4)F(7)/C(4)F(7)(-)), 3.34 eV (C(5)F(9)/C(5)F(9)(-)), and 3.21 eV
      (C(6)F(11)/C(6)F(11)(-)).

PMID- 15161298
TI  - Formation of piezoelectric single-crystal nanorings and nanobows.
AB  - Bending of polar-surface-dominated (PSD) nanobelts of ZnO can be explained by one
      of two processes: electrostatic neutralization of the dipole moment via
      deformation (called an electrostatic polar charge model) or imbalances between
      surface tensions via surface-termination induced stresses. This article presents
      experimental data on the structural features of nanorings and nanobows formed by
      bending single-crystal, PSD ZnO nanobelts. Our data exclusively support the
      electrostatic polar charge model as the dominant mechanism for bending.

PMID- 15161299
TI  - Intersystem crossing versus electron transfer in porphyrin-based donor-bridge
      acceptor systems: influence of a paramagnetic species.
AB  - We have investigated how the spin state of an acceptor influences the
      photophysical processes in a donor-bridge-acceptor (D-B-A) system. The system of
      choice has zinc porphyrin as the electron donor and high- or low-spin iron(III)
      porphyrin as the acceptor. The spin state of the acceptor porphyrin is switched
      simply by coordinating imidazole ligands to the metal center. The D-A center
      center distance is 26 A, and the bridging chromophore varies from pi-conjugated
      to a sigma-bonded system. The presence of a high-spin iron(III) porphyrin in such
      systems has previously been shown to significantly enhance intersystem crossing
      in the remote zinc porphyrin donor, whereas no significant electron transfer to
      the iron porphyrin acceptor was observed, even though the thermodynamics would
      allow for photoinduced electron transfer. Here, we demonstrate that by switching
      the acceptor to a low-spin state, the dominating photophysical process is
      drastically changed; the low-spin system shows long-range electron transfer on
      the picosecond time-scale, and intersystem crossing occurs at its "normal" rate.

PMID- 15161300
TI  - Assignments of carbon NMR resonances for microcrystalline ubiquitin.
AB  - Solid-state NMR 2D spectroscopy was used to correlate carbon backbone and side
      chain chemical shifts for uniformly (13)C,(15)N-enriched microcrystalline
      ubiquitin. High applied field strengths, 800 MHz for protons, moderate proton
      decoupling fields, 80-100 kHz, and high magic angle sample spinning frequencies,
      20 kHz, were used to narrow the most of the carbon line widths to 0.5-0.8 ppm.
      Homonuclear magnetization transfer was effected by matching the proton RF field
      to the spinning frequency, the so-called dipolar-assisted rotational resonance
      (DARR) (Takegoshi, K.; Nakamura, S.; Terao, T. Chem. Phys. Lett. 2001, 344, 631
      637), and a mixing time of 20 ms was used to maximize the intensity of one-bond
      transfers between carbon atoms. This polarization transfer sequence resulted in
      roughly 14% transfer efficiencies for directly bonded carbon pairs and 4%
      transfer efficiencies for carbons separated by a third carbon. With this simple
      procedure, the majority of the one-bond correlations was observed with moderate
      transfer efficiencies, and many two-bond correlations were also observed with
      weaker intensities. Spin systems could be identified for more than half of the
      amino acid side chains, and site-specific assignments were readily possible via
      comparison with 400 MHz (15)N-(13)C-(13)C correlation spectroscopy (described
      separately).

PMID- 15161301
TI  - Spin-orbit-induced anomalous pH-dependence in (1)H NMR spectra of Co(III) amine
      complexes: a diagnostic tool for structure elucidation.
AB  - The pH-dependent (1)H NMR characteristics of a series of Co(III)-(polyamin)-aqua
      and Co(III)-(polyamin)-(polyalcohol) complexes, [Co(tach)(ino-kappa(3)
      O(1,3,5))](3+) (1(3+)), [Co(tach)(ino-kappa(3)-Omicron(1,2,6))](3+) (2(3+)),
      [Co(tach)(taci-kappa-Nu(1)-kappa(2)-O(2,6))](3+) (3(3+)), [Co(ditame)(H(2)O)](3+)
      (4(3+)), and [Co(tren)(H(2)O)(2)](3+) (5(3+)), were studied in D(2)O by means of
      titration experiments (tach = all-cis-cyclohexane-1,3,5-triamine, ino = cis
      inositol, taci = 1,3,5-triamino-1,3,5-trideoxy-cis-inositol, tren = tris(2
      aminoethyl)amine, ditame = 2,2,6,6-tetrakis-(aminomethyl)-4-aza-heptane). A
      characteristic shift was observed for H(-C) hydrogen atoms in the alpha-position
      of a coordinated amino group upon deprotonation of a coordinated oxygen donor.
      For a cis-H-C-N-Co-O-H arrangement, deprotonation of the oxygen donor resulted in
      an additional shielding (shift to lower frequency) of the H(-C) proton, whereas
      for a trans-H-C-N-Co-O-H arrangement, deprotonation resulted in a deshielding
      (shift to higher frequency). The effect appears to be of rather general nature:
      it is observed for primary (1(3+)-5(3+)), secondary (4(3+)), and tertiary (5(3+))
      amino groups, and for the deprotonation of an alcohol (1(3+)-3(3+)) or a water
      (4(3+), 5(3+)) ligand. Spin-orbit-corrected density functional calculations show
      that the high-frequency deprotonation shift for the trans-position is largely
      caused by a differential cobalt-centered spin-orbit effect on the hydrogen
      nuclear shielding. This effect is conformation dependent due to a Karplus-type
      behavior of the spin-orbit-induced Fermi-contact shift and thus only significant
      for an approximately antiperiplanar H-C-N-Co arrangement. The differential spin
      orbit contribution to the deprotonation shift in the trans-position arises from
      the much larger spin-orbit shift for the protonated than for the deprotonated
      state. This is in turn due to a trans-effect of the deprotonated (hydroxo or
      alkoxo) ligand, which weakens the trans Co-N bond and thereby interrupts the
      Fermi-contact mechanism for transfer of the spin-orbit-induced spin polarization
      to the hydrogen nucleus in question. The unexpectedly large long-range spin-orbit
      effects found here for 3d metal complexes are traced back to small energy
      denominators in the perturbation theoretical expressions of the spin-orbit
      shifts.

PMID- 15161302
TI  - Competitive Na(+) and Rb(+) binding in the minor groove of DNA.
AB  - Sequence-dependent coordination of alkali ions to the nucleotide bases in the
      minor groove of AT-tract B-DNA has recently been inferred from X-ray
      crystallography, solution NMR and computer simulations. Here, we present new
      (23)Na and (87)Rb magnetic relaxation dispersion (MRD) data that demonstrate
      competitive and long-lived binding of Na(+) and Rb(+) ions in the minor groove of
      the B-DNA duplex [d(CGCGAATTCGCG)](2). The Na(+)/Rb(+) selectivity of the minor
      groove is found to be weak, consistent with local structural flexibility. The ion
      occupancies derived from the MRD data are substantially higher than previously
      reported, suggesting that groove-bound ions significantly influence the
      energetics and structural polymorphism of DNA in vivo. For example, in the
      presence of 0.20 M Na(+) and 0.56 M Rb(+) at 4 degrees C, the ApT site in the
      minor groove is occupied by a Rb(+) ion, a Na(+) ion, or a water molecule 40, 10,
      and 50% of the time, respectively. In the absence of Rb(+), the Na(+) occupancy
      increases to 50%. At 4 degrees C, the mean residence time of groove-bound ions is
      0.2 +/- 0.1 micros for Rb(+) and 10 ns to 100 micros for Na(+). A shorter
      correlation time of 2 ns is attributed to counterions bridging cross-strand
      phosphate groups.

PMID- 15161303
TI  - Proton-mediated dynamics of the alkaline conformational transition of yeast iso-1
      cytochrome c.
AB  - The kinetics of the alkaline conformational transition of a Lys 73-->His variant
      of iso-1-cytochrome c have been investigated using pH jump stopped-flow methods
      to probe the nature of the ionizable "trigger" group for this conformational
      change. This mutation moves the pK(a) of the ligand replacing Met 80 from about
      10.5 to approximately 6.6 and has unmasked two other ionizable groups, besides
      the ligand replacing Met 80, that modulate the kinetics of this process. The
      results are discussed in terms of the impact of ionization equilibria on protein
      folding mechanisms.

PMID- 15161304
TI  - Aza-amino acid scan for rapid identification of secondary structure based on the
      application of N-Boc-aza(1)-dipeptides in peptide synthesis.
AB  - Azapeptides, peptide analogues in which the alpha-carbon of one or more of the
      amino acid residues is replaced with a nitrogen atom, exhibit propensity for
      adopting beta-turn conformations. A general protocol for the synthesis of
      azapeptides without racemization on solid phase has now been developed by
      introducing the aza-amino acid residue as an N-Boc-aza(1)-dipeptide. This
      approach has been validated by the synthesis of six N-Boc-aza(1)-dipeptides and
      their subsequent introduction into analogues of the C-terminal peptide fragment
      of the human calcitonin gene-related peptide (hCGRP). By performing an aza-amino
      acid scan of such antagonist peptides, a set of aza-hCGRP analogues was
      synthesized to examine the relationship between turn secondary structure and
      biological activity.

PMID- 15161305
TI  - Reduction of strained polycycles: how much strain can a pyrene anion take?
AB  - The reduction of a series of [n](2,7)pyrenophanes (n = 7-10) with lithium or
      potassium metal shows that the strain in the system, controlled by the length of
      the tether, determines the nature of the reduction products. The reduction of
      [7](2,7)pyrenophane (2) and [2]metacyclo[2](2,7)pyrenophane (3) leads to
      reductive dimerization followed by novel intramolecular sigma-bond formation as a
      means of escaping strained anti-aromaticity. [8](2,7)Pyrenophane (4) affords only
      reductive dimerization, and no two-electron reduction is observed. The reduction
      of [9](2,7) pyrenophane (5) and [10](2,7)pyrenophane (6) leads to reductive
      dimerization, followed by the formation of a dianionic anti-aromatic species,
      which eventually cleaves the solvent, THF-d(8). The similarity between the
      reduction of the latter systems and the reduction of pyrene (1) is discussed.

PMID- 15161306
TI  - Transformation of zirconocene-olefin complexes into zirconocene allyl hydride and
      their use as dual nucleophilic reagents: reactions with acid chloride and 1,4
      diketone.
AB  - Zirconocene-olefin complexes Cp(2)Zr(H(2)C=CHR), prepared in benzene-THF at 0
      degrees C, react with acid chlorides to provide homoallylic alcohols. The key is
      an equilibrium between the zirconocene-olefin complexes and the corresponding
      zirconocene allyl hydride complexes via allylic C-H bond cleavage of the
      coordinating alkenes. Furthermore, the zirconocene-olefin complexes are also
      available for the reaction with 1,4-diketone to afford anti-1,4-diols with
      excellent diastereoselectivity. Thus, Cp(2)Zr(H(2)C=CHR) serves as a donor of
      both hydride and an allylic group. These reactions also proceed efficiently by
      using zirconocene-olefin complexes, derived from Cp(2)ZrCl(2), Mg metal, and 1
      alkenes.

PMID- 15161307
TI  - A model for describing the thermodynamics of multivalent host-guest interactions
      at interfaces.
AB  - A model has been described for interpreting the binding of multivalent molecules
      to interface-immobilized monovalent receptors through multiple, independent
      interactions. It is based on the concept of effective concentration, C(eff),
      which has been developed before for multivalent binding in solution and which
      incorporates effects of lengths and flexibilities of linkers between interacting
      sites. The model assumes: (i). the interactions are independent, (ii). the
      maximum number of interactions, p(max), is known, (iii). C(eff) is estimated from
      (simple) molecular models. Simulations of the thermodynamics and kinetics of
      multivalent host-guest binding to interfaces have been discussed, and competition
      with a monovalent competitor in solution has been incorporated as well. The model
      was successfully used to describe the binding of a divalent guest to self
      assembled monolayers of a cyclodextrin host. The adsorption data of more complex
      guest-functionalized dendrimers, for which p(max) was not known beforehand, was
      interpreted as well. Finally, it has been shown that the model can aid to
      deconvolute contributions of multivalency and cooperativity to stability
      enhancements observed for the adsorption of multivalent molecules to interfaces.

PMID- 15161308
TI  - Mixed complexes formed by lithioacetonitrile and chiral lithium amides:
      observation of (6)li,(15)N and (6)Li,(13)C couplings due to both C-Li and N-Li
      contacts.
AB  - NMR spectroscopic studies have been performed on the mixed complexes formed by
      the lithium salt of acetonitrile (LiCH(2)CN) and the chiral lithium amides Li-(S)
      N-(2-methoxybenzyl)-1-amino-1-phenyl-2-ethoxyethane (Li-1) and Li-(S)-N-isopropyl
      2-amino-1-phenyl-3-methoxypropane (Li-2) in diethyl ether and tetrahydrofuran
      solvent. In diethyl ether Li-1 and LiCH(2)CN form a mixed dimeric (1:1) complex,
      while Li-2 and LiCH(2)CN form a mixed trimeric (2:1) complex. The dimer undergoes
      fast exchange between ketenimine and bridged structures. Both (1)J((15)N,(6)Li)
      and (1)J((13)C,(6)Li) couplings were observed for the respectively isotopically
      labeled compounds. In the trimeric complex the CH(2)CN anion also undergoes fast
      degenerate exchange between ketenimine and bridged structures, and the complex
      appears C(2)-symmetric on the NMR spectroscopy time scale. Both the dimer and
      trimer complexes have the bridged acetonitrile anion in common, as indicated by
      the highly shielded alpha-carbon (13)C NMR shifts (delta -6.1 and -7.4,
      respectively). In tetrahydrofuran only N-metalated mixed LiCH(2)CN dimers were
      observed for both Li-1 and Li-2 with the less shielded (13)C NMR shifts of delta 
      2.5 and -2.2 for the alpha-carbon of LiCH(2)CN of the complexes.

PMID- 15161309
TI  - Transition metal-stabilized arenium cations: protonation of arenes dihapto
      coordinated to pi-basic metal fragments.
AB  - A series of metal complexes was synthesized in which arenes were dihapto
      coordinated to pi-basic metal fragments having the general form [TpM(pi
      acid)(L)], where Tp = hydridotris(pyrazolyl)borate, M = rhenium, molybdenum, or
      tungsten, pi-acid = CO or NO(+), and L = 1-methylimidazole, 1-butylimidazole,
      pyridine, or trimethylphosphine. The arene complexes were shown to be
      significantly more basic than the analogous pentaammineosmium(II) arene complexes
      and were protonated by moderate acids to give remarkably stable eta(2) and eta(3)
      arenium cation complexes. A crystal structure of [TpRe(CO)(MeIm)(5,6-eta(2)-2H
      anisolium)](OTf) confirmed the eta(2) coordination of the anisolium ligand, but
      suggests a weak long-range interaction between the metal and C1 of the anisolium.

PMID- 15161310
TI  - Experimental and theoretical evidence for homogeneous catalysis in the gas-phase
      reaction of SiH(2) with H(2)O (and D(2)O): a combined kinetic and quantum
      chemical study.
AB  - Time-resolved kinetic studies of the reaction of silylene, SiH(2), with H(2)O and
      with D(2)O have been carried out in the gas phase at 297 K and at 345 K, using
      laser flash photolysis to generate and monitor SiH(2). The reaction was studied
      independently as a function of H(2)O (or D(2)O) and SF(6) (bath gas) pressures.
      At a fixed pressure of SF(6) (5 Torr), [SiH(2)] decay constants, k(obs), showed a
      quadratic dependence on [H(2)O] or [D(2)O]. At a fixed pressure of H(2)O or
      D(2)O, k(obs) values were strongly dependent on [SF(6)]. The combined rate
      expression is consistent with a mechanism involving the reversible formation of a
      vibrationally excited zwitterionic donor-acceptor complex, H(2)Si...OH(2) (or
      H(2)Si...OD(2)). This complex can then either be stabilized by SF(6) or it reacts
      with a further molecule of H(2)O (or D(2)O) in the rate-determining step. Isotope
      effects are in the range 1.0-1.5 and are broadly consistent with this mechanism.
      The mechanism is further supported by RRKM theory, which shows the association
      reaction to be close to its third-order region of pressure (SF(6)) dependence. Ab
      initio quantum calculations, carried out at the G3 level, support the existence
      of a hydrated zwitterion H(2)Si...(OH(2))(2), which can rearrange to hydrated
      silanol, with an energy barrier below the reaction energy threshold. This is the
      first example of a gas-phase-catalyzed silylene reaction.

PMID- 15161311
TI  - Anisotropic in-plane gradients of poly(acrylic acid) formed by
      electropolymerization with spatiotemporal control of the electrochemical
      potential.
AB  - Laterally varying thickness gradients of poly(acrylic acid) (PAA) were formed by
      Zn(II)-catalyzed electropolymerization of acrylic acid (AA) in the presence of an
      in-plane electrochemical potential gradient applied to Au working electrodes. In
      the static potential gradient (SPG) approach, two ends of a Au working electrode
      were clamped at distinct potentials for the duration of the electropolymerization
      process, thereby generating a time-independent in-plane electrochemical potential
      gradient, V(x). A dynamic potential gradient (DPG) approach was also used, in
      which the two end potentials were varied in time, while maintaining a constant
      voltage offset, to generate an in-plane electrochemical potential gradient,
      V(x,t). Because the kinetics of heterogeneous electron transfer vary with the
      local overpotential, these two methods produce PAA films with laterally varying
      thickness gradients, although they exhibit different spatial characteristics. X
      ray photoelectron spectroscopy (XPS) and surface plasmon resonance (SPR) imaging
      were used to characterize the PAA gradients. The in-plane thickness variations of
      PAA gradients formed by both SPG and DPG approaches agree with predictions of the
      Butler-Volmer equation at small absolute overpotentials, while at large
      (negative) overpotentials, mass transport dominates, and the thickness reaches a
      plateau value independent of local potential. DPG-produced PAA gradients are
      generally broader than SPG gradients with the same initial potential and
      comparable effective growth time, indicating that the DPG approach is more
      suitable for formation of thicker gradients.

PMID- 15161316
TI  - Computerized planning of cryosurgery using cryoprobes and cryoheaters.
AB  - In a typical minimally invasive cryoprocedure, multiple cryoprobes are inserted
      into the tissue with the goal of maximizing cryoinjury within a predefined target
      region, while minimizing cryoinjury to the surrounding tissues. A temperature
      controlled electrical heater has been developed recently by this research team,
      in order to assist in limiting the cryoinjury to the target region. The new
      device has been termed a 'cryoheater,' and it can work with any cryosurgical
      cooling technique. A prototype computerized planning tool has been presented
      recently by this research team, which helps to determine the best locations in
      which to insert the cryoprobes. This prototype was designed for cryoprobes only.
      The planning procedure utilized a novel iterative optimization technique, based
      on a force-field analogy. The combination of cryoheaters with computerized
      planning is the subject matter of this report. The current report includes a
      review of cryoheater development, and presents an improved cryosurgery planning
      tool which incorporates cryoheaters.

PMID- 15161317
TI  - Assessing pH and oxygenation in cryotherapy-induced cytotoxicity and tissue
      response to freezing.
AB  - The microenvironmental pH and oxygenation is known to influence tumor cell
      response to heat, radiation, photodynamic and even chemotherapy. We have studied
      the previously untested influence of acidity and hypoxia on tumor and endothelial
      cell sensitivity to freezing. In addition, we have measured changes in
      oxygenation in vivo in murine FSaII fibrosarcomas after freeze injury. A low pH
      or low oxygenation environment was found to increase the sensitivity of tumor and
      endothelial cells to freezing at -20 degrees C or -40 degrees C in vitro.
      However, low pH and low oxygenation combined did not further increase
      cryosensitivity of the cells. In vivo, tumor oxygenation after freeze injury was
      studied immediately or 1-3 days after a standard freezing protocol was applied to
      FSaII tumors ranging from 250-500 mm3 grown in the rear-limb of C3H mice. Tumor
      oxygenation at the edge of the iceball was found to transiently increase 1-2
      hours after freezing. At 1-3 days after freezing, a treatment that delayed FSaII
      tumor growth by approximately 1.5-fold, the mean tumor oxygenation was
      significantly increased by up to 2.5-fold from a control level of 5 mmHg partial
      pressure of oxygen (pO2), especially at the periphery of the tumor. We conclude
      that manipulation of pH or oxygenation has potential to increase the anti-tumor
      effects of minimally invasive cryosurgical techniques. Furthermore, the dynamic
      changes in oxygenation after freeze injury in vivo suggests value in combining
      cryotherapy with treatments dependent on oxygenation levels. Ultimately, these
      may be routes to more reliable treatment response with fewer recurrences.

PMID- 15161318
TI  - In treating localized prostate cancer the efficacy of cryoablation is independent
      of DNA ploidy type.
AB  - While the prognostic value of DNA ploidy has been well established for radical
      prostatectomy, external beam radiation, brachytherapy and androgen deprivation
      therapy its role as a survival outcome predictor for prostate cancer patients
      treated with cryoablation has not yet been examined. Anecdotal evidence
      suggesting that cryoablation may be independent of DNA ploidy type led to the
      implementation of the current study. Retrospective analysis of data including
      flow digital cytometry was performed on 447 archival specimens taken from
      patients who had undergone cryosurgical ablation of primary prostate cancer. Five
      year biochemical disease free survivals (bDFS) (defined as PSA thresholds of 0.5
      and 1.0 ng/ml) were determined with Kaplan-Meier analysis. Patients were grouped
      according to DNA ploidy types then stratified by Gleason grade, risk group, pre
      surgical PSA level, and disease stage. Mean and median age of the cohort was 65
      and 64.6 years. Mean follow-up was 65.7 months. The DNA ploidy status of the
      population was found to be 59% diploid, 13% tetraploid, and 28% aneuploid. Using
      PSA < 1.0 ng/ml criterion, the bDFS rates for diploid, tetraploid, and aneuploid
      were 78%, 75%, and 79% respectively. The bDFS rates using a PSA < 0.5 ng/ml
      criterion were 67%, 59%, and 69% for diploid, tetraploid, and aneuploid groups.
      No significant outcome differences were found in stratified analysis. This
      investigation demonstrates that the efficacy of cryoablation is independent of
      DNA ploidy type.

PMID- 15161319
TI  - HDR brachytherapy with surface applicators: technical considerations and
      dosimetry.
AB  - HDR surface molds offer an alternative radiotherapy modality to electrons for the
      treatment of skin lesions. Treatment planning and dosimetry are discussed for two
      types of surface molds used in our clinic. Standard rectangular applicators are
      used on a variety of sites where surface curvature is minimal. In these cases an
      idealized planar geometry is used for treatment planning dose calculations. The
      calculations yield treatment dose uniformity at the prescription depth in tissue
      as well as skin dose, as a percentage of the treatment dose, and its dose
      uniformity. The availability of optimization techniques results in superior dose
      uniformity at depth but the dose at the skin has to be carefully evaluated. We
      have studied the dependence of these dosimetric parameters on the size of the
      surface mold and the type of optimization procedure used in the dosimetry
      calculations. The second type of surface applicator involves the use of a
      customized silicone rubber mold attached to a thermoplastic mask of the patient.
      We have used them to treat lesions of the face where surface curvatures are
      appreciable and reproducibility of setup is more critical. In these cases a CT
      data set is used for reconstruction of the catheters, activation of relevant
      dwell positions and dosimetry, including optimization. Towards establishing
      effective methods for quality assurance of the optimized HDR surface mold
      planning calculations, we have compared their dosimetry to both a classical
      brachytherapy system and to one based on an analytical model of the applicator.
      The classical system yields an independent verification of the integrated
      activity used in the planning calculations, whereas the analytical model is used
      to evaluate depth dose dependence on mold size and optimization.

PMID- 15161320
TI  - High dose rate brachytherapy: its clinical applications and treatment guidelines.
AB  - Brachytherapy has the advantage of delivering a high dose to the tumor while
      sparing the surrounding normal tissues. With proper case selection and delivery
      technique, high-dose-rate (HDR) brachytherapy has great promise, because it
      eliminates radiation exposure, allows short treatment times, and can be performed
      on an outpatient basis. Additionally, use of a single-stepping source, allows
      optimization of dose distribution by varying the dwell time at each dwell
      position. However, when HDR brachytherapy is used, the treatments must be
      executed carefully, because the short treatment times do not allow any time for
      correction of errors, and mistakes can result in harm to patients. Hence, it is
      very important that all personnel involved in HDR brachytherapy be well trained
      and be constantly alert. It is expected that the use of HDR brachytherapy will
      greatly expand over the next decade and that refinements will occur primarily in
      the integration of imaging (computed tomography, magnetic resonance imaging,
      intraoperative ultrasonography) and optimization of dose distribution. It is
      anticipated that better tumor localization and normal tissue definition will help
      to optimize dose distribution to the tumor and reduce normal tissue exposure. The
      development of well-controlled randomized trials addressing issues of efficacy,
      toxicity, quality of life, and costs-versus-benefits will ultimately define the
      role of HDR brachytherapy in the therapeutic armamentarium.

PMID- 15161321
TI  - Lung cancer radiation therapy: Monte Carlo investigation of "under dose" by high
      energy photons.
AB  - Loss of electronic equilibrium in lung tissue causes a build-up region in the
      tumor. Increasing the photon energy increases the depth at which electronic
      equilibrium is reestablished within the lung tumor. This study uses the Monte
      Carlo code PENELOPE for simulations of radiation treatment of tumor surrounded by
      lung. Six MV photons were compared to 15 MV photons using four beam arrangements
      in both homogeneous and heterogeneous media. The experimental results demonstrate
      that for every beam arrangement in heterogeneous media 15 MV photons delivered 5%
      to 10% lower dose to the tumor periphery than 6 MV photons. The simulations also
      show that in axial coplanar treatment plans, the loss of electronic equilibrium
      was greatest in the coronal plane. In conclusion there is a tumor sparing effect
      at the tumor-lung interface that is a function of beam energy. As an alternative
      to increasing beam energy, the addition of multiple beam angles with lower energy
      photons improved target coverage. If higher energy beams are required for
      patients with large separation, then adding multiple beam angles does offer some
      improved target coverage. The non-coplanar technique with the lower energy
      photons covered the tumor with a greatest isodose at the tumor periphery without
      tangential sparing in the coronal plane.

PMID- 15161322
TI  - Improved targeting of photosensitizers by intratumoral administration of
      immunoconjugates.
AB  - Biodistribution of technetium (99mTc) labeled hematoporphyrin derivative (HpD,
      Photosan-3) conjugated to a monoclonal antibody to carcinoembryonic antigen (anti
      CEA) was compared following intravenous (i.v.) and intratumoral (i.t.)
      administration in solid Ehrlich ascites tumor bearing mice. Images of mice at
      different time intervals were acquired after injection of radiolabeled PS-3 in
      either conjugated or unconjugated forms. Quantitative estimation of the
      radiolabel in different tissues was performed by selecting the different region
      of interests (ROIs). Maximum accumulation of both free and antibody conjugated PS
      3 following i.v. administration was observed in liver followed by tumor.
      Tumor/muscle (T/N) ratio was more with free PS-3 compared to conjugated PS-3.
      Pharmacokinetics of free and conjugated PS-3 was also different with faster
      accumulation of conjugated PS-3 in the tumor. With intratumoral administration of
      anti-CEA-PS-3-99mTc, specific accumulation and retention of the sensitizer was
      observed in the tumor tissue. Since, direct injection of antibody conjugated
      photosensitizer into the tumor resulted in longer retention of the dye in the
      tumor with no accumulation in the normal tissues, the present results imply that
      the toxicity to normal tissues could be reduced significantly with selective
      destruction of the tumor following photodynamic treatment with the use of i.t.
      administration of specific antibodies conjugated to photosensitizers.

PMID- 15161323
TI  - The impact of mid-treatment MRI on defining boost volumes in the radiation
      treatment of glioblastoma multiforme.
AB  - Radiation therapy is a central modality in the treatment of glioblastoma
      multiforme (GBM). Integral to adequate radiation therapy delivery is the
      appropriate determination of tumor volume and extent at the time treatment is
      being delivered. As a matter of routine practice, radiation therapy treatment
      fields are designed based on tumor volumes evident on pre-operative or immediate
      post-operative MRIs; another MRI is generally not obtained for planning boost
      fields. In some instances the time interval from surgery to radiotherapy
      initiation is up to 5 weeks and the boost or "cone-down phase" commences 4-5
      weeks later. The contrast enhanced T1 MRI may not be a totally reliable indicator
      of active tumor, especially in regions where such blood-brain barrier breakdown
      has not occurred. Moreover, these volumes may change during the course of
      treatment. This may lead to a geographic miss when mid-treatment boost volumes
      are designed based on a pre-radiotherapy MRI. The goal of this study is to
      examine how a mid-treatment MRI impacts the delineation and definition of the
      boost volume in GBM patients in comparison to the pre-treatment MRI scan,
      particularly when the tumor-specific agent Motexafin-Gadolinium is used.

PMID- 15161324
TI  - Evolving strategies for insulin delivery and therapy.
AB  - It has now been conclusively proven that adequate control of blood glucose delays
      or prevents the progression of diabetic complications. In order to achieve the
      suggested targets for glycaemic control necessary to reduce the incidence of
      diabetic complications, it has been established that a more intensive insulin
      regimen requiring multiple insulin injections is required for patients with type
      1 diabetes mellitus. For patients with type 2 diabetes, oral antidiabetic therapy
      is generally used initially, but given the natural history of type 2 diabetes and
      the need to achieve improved glycaemic control, earlier use of insulin has been
      promoted. However, the use of insulin in more intensive regimens for the patient
      with type 1 diabetes or for earlier treatment of the patient with type 2 diabetes
      is not routine. Many factors are responsible for this observation. Nevertheless,
      available device options such as insulin pens or insulin pumps are routinely
      available for implementation of intensive insulin therapy. However, a major
      limitation for advancing to intensive insulin therapy is that the only viable way
      to administer insulin is through injection. Delivery options that use dermal,
      nasal and oral approaches have been explored. The oral approach may include
      gastrointestinal, buccal or pulmonary uptake. Recent evidence shows that delivery
      of insulin via the oral cavity with uptake occurring in the pulmonary alveoli may
      be the most viable clinical option in the future.

PMID- 15161325
TI  - Mucosal and systemic fungal infections in patients with AIDS: prophylaxis and
      treatment.
AB  - In countries where highly active antiretroviral therapy (HAART) is widely
      available, a decrease in the incidence of fungal infections has been observed in
      the last 5 years compared with countries that cannot afford this treatment. Even
      refractory fungal infections may be controlled when HAART is given to patients,
      and end-stage AIDS infections, such as aspergillosis, are now only infrequently
      seen. In contrast, fungal infections in certain regions, such as penicilliosis in
      Southeast Asia or cryptococcosis in Sub-Saharan Africa, are a growing problem.
      Antifungal therapy for documented infections has not changed very much during
      recent years; however, new drugs such as caspofungin and voriconazole may be more
      effective in the treatment of opportunistic fungal infections, in particular,
      those involving resistant organisms. Secondary antifungal prophylaxis for many
      opportunistic pathogens can now be temporarily or even permanently discontinued
      in many HIV-positive patients who have a marked improvement in immune function
      parameters, such as CD4(+) cell counts, after initiation of HAART. The link
      between effective virustatic control of HIV infection and a decreasing incidence
      of fungal infections has been recognised; and so, despite the availability of
      very effective new antifungal drugs, the cornerstone of treatment and prevention
      of opportunistic fungal infections in patients with HIV infection is effective
      antiretroviral therapy including protease inhibitors.

PMID- 15161327
TI  - Zoledronic acid: a review of its use in patients with advanced cancer.
AB  - Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of
      osteoclast-mediated bone resorption and is used in the management of patients
      with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over
      15 minutes. In the treatment of bone metastases, zoledronic acid is the first and
      only bisphosphonate to demonstrate efficacy in patients with a broad range of
      tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose
      of zoledronic acid showed good efficacy in the treatment of patients with
      hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic
      acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum
      calcium concentrations 10 days after administration. In conjunction with
      antineoplastic therapy, zoledronic acid was an effective long-term (up to 25
      months) treatment for skeletal-related events in patients with bone metastases
      associated with multiple myeloma or solid tumours. In patients with bone
      metastases secondary to breast cancer or bone lesions from myeloma, zoledronic
      acid was at least as effective as pamidronic acid, based on assessments of
      skeletal-related events 25 months after the start of treatment. In addition,
      compared with pamidronic acid, the overall risk of developing skeletal
      complications, including hypercalcaemia of malignancy, was significantly reduced
      in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid
      reduced the risk of patients with breast cancer developing a skeletal-related
      event by an additional 20%. Zoledronic acid was significantly more effective than
      placebo on most efficacy measures in patients with bone metastases secondary to
      other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to
      15 months. Preliminary data indicate that its efficacy in these patients is
      sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic
      acid in the treatment of prostate cancer were consistent with those of other
      bisphosphonates, and cost-effectiveness ratios were within limits considered
      acceptable economic value. Zoledronic acid was generally well tolerated, with a
      tolerability profile similar to that of pamidronic acid and placebo. As with
      other bisphosphonates, deterioration of renal function has occasionally been
      reported in patients receiving zoledronic acid and monitoring of serum creatinine
      is recommended during treatment. The efficacy of zoledronic acid is therefore
      well established in patients with hypercalcaemia of malignancy and, for up to 25
      months, in the treatment of complications arising from metastatic bone disease in
      patients with multiple myeloma or solid tumours. The clinical profile of
      zoledronic acid compares favourably with that of pamidronic acid in patients with
      cancer and zoledronic acid has a more convenient administration schedule with the
      potential for better compliance. Thus, zoledronic acid is an effective
      bisphosphonate and is positioned to play an important role in the management of
      advanced cancer patients with bone metastases.

PMID- 15161326
TI  - Medical lipid-regulating therapy: current evidence, ongoing trials and future
      developments.
AB  - Coronary heart disease (CHD) is a major cause of morbidity and mortality
      worldwide. Elevated low density lipoprotein-cholesterol (LDL-C) and reduced high
      density lipoprotein-cholesterol (HDL-C) levels are well recognised CHD risk
      factors, with recent evidence supporting the benefits of intensive LDL-C
      reduction on CHD risk. Such observations suggest that the most recent National
      Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL-C
      targets of 2.6 mmol/L, may result in under-treatment of a significant number of
      patients and form the basis for the proposed new joint European Societies
      treatment targets of 2 and 4 mmol/L, respectively, for LDL and total cholesterol.
      HMG-CoA reductase inhibitors (statins) reduce LDL-C by inhibiting the rate
      limiting step in cholesterol biosynthesis and reduced CHD event rates in primary
      and secondary prevention trials. The magnitude of this effect is not fully
      accounted for by LDL-C reduction alone and may relate to effects on other lipid
      parameters such as HDL-C and apolipoproteins B and A-I, as well as additional
      anti-inflammatory effects. With increasing focus on the benefits of intensive
      cholesterol reduction new, more efficacious statins are being developed.
      Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in
      LDL-C of up to 55%, with about 80% of patients reaching European LDL-C treatment
      targets at the 10 mg/day dosage. The Heart Protection Study (HPS) demonstrated
      that LDL-C reduction to levels as low as 1.7 mmol/L was associated with
      significant clinical benefit in a wide range of high-risk individuals, including
      patients with type 2 diabetes mellitus, or peripheral and cerebrovascular
      disease, irrespective of baseline cholesterol levels, with no apparent lower
      threshold for LDL-C with respect to risk. Various large endpoint trials,
      including Treating to New Targets (TNT) and Study of Effectiveness of Additional
      reductions in Cholesterol and Homocysteine (SEARCH) will attempt to further
      address the issue of optimal LDL-C reduction. At low LDL-C levels, HDL-C becomes
      an increasingly important risk factor and is the primary lipid abnormality in
      over half of CHD patients, with the Fenofibrate Intervention and Event Lowering
      in Diabetes (FIELD) study set to assess the effect of raising HDL-C on
      cardiovascular events in patients with low HDL-C and LDL-C levels below 3 mmol/L.
      A variety of agents are being developed, which affect both LDL-C and HDL-C
      metabolism, including inhibitors of acyl-coenzyme A-cholesterol acyl transferase,
      microsomal transfer protein and cholesterol ester transfer protein, as well as
      specific receptor agonists. Ezetimibe is a selective cholesterol absorption
      inhibitor, which produces reductions in LDL-C of up to 25 and 60% reduction in
      chylomicron cholesterol content with a 10 mg/day dosage. A 1 mmol/L reduction in
      LDL-C results in a 25% reduction in cardiovascular risk, independent of baseline
      LDL-C levels. Growing evidence supports the concept that lower is better for LDL
      C and that increasing HDL-C represents an important therapeutic target.
      Furthermore, there is growing appreciation of the role of inflammation in
      atherogenesis. Consequently, increasing numbers of people should receive lipid
      regulating therapy with the development of newer agents offering potential
      mechanisms of optimising lipid profiles and thus risk reduction. In addition, the
      pleiotropic anti-inflammatory effects of lipid lowering therapy may provide
      further risk reduction.

PMID- 15161328
TI  - Letrozole: a review of its use in postmenopausal women with breast cancer.
AB  - Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor
      administered orally once daily, has shown efficacy in the treatment of
      postmenopausal women with early-stage or advanced, hormone-sensitive breast
      cancer. In early-stage disease, extending adjuvant endocrine therapy with
      letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free
      survival; compared with placebo there was a 43% relative reduction in disease
      recurrences or new contralateral breast tumours at a median follow-up of 2.4
      years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen
      in postmenopausal women with untreated primary disease favour letrozole. In
      advanced breast cancer, letrozole was superior to tamoxifen as first-line
      treatment; time to disease progression was significantly longer (9.4 vs 6.0
      months, p < 0.0001) and objective response rate was significantly greater with
      letrozole, but median overall survival was similar between groups. For second
      line therapy of advanced breast cancer that had progressed on antiestrogen
      therapy, letrozole showed efficacy equivalent to that of anastrozole and similar
      to or better than that of megestrol acetate. Letrozole is generally well
      tolerated and has a similar tolerability profile to tamoxifen; the most common
      treatment-related adverse events were hot flushes, nausea and hair thinning. In
      patients with tumours that had progressed on antiestrogen therapy, letrozole was
      tolerated as least as well as, or better than, anastrozole or megestrol acetate.
      In the trial of extended adjuvant therapy, adverse events reported more
      frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and
      arthritis. The long-term effects of letrozole on bone mineral density or lipid
      profile have not been determined and these parameters may require monitoring. In
      several pharmacoeconomic modelling studies from various public healthcare system
      perspectives, letrozole was considered a cost effective choice for first-line (vs
      tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast
      cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective
      in the treatment of postmenopausal women with early-stage or advanced breast
      cancer. The efficacy, cost effectiveness and favourable tolerability profile of
      letrozole are reflected in current treatment guidelines recommending the drug as
      first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen
      for first-line treatment and is at least as effective as standard second-line
      treatments in disease that has progressed on antiestrogen therapy. For early
      stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and
      prolongs disease-free survival when administered after the standard 5-year period
      of adjuvant tamoxifen therapy.

PMID- 15161330
TI  - The management of hypertension in the overweight and obese patient: is weight
      reduction sufficient?

PMID- 15161332
TI  - Is there a future for neural transplantation?
AB  - Traditionally neural transplantation has had as its central tenet the replacement
      of missing neurons that have been lost because of neurodegenerative processes, as
      exemplified by diseases such as Parkinson disease (PD). However, the
      effectiveness and widespread application of this approach clinically has been
      limited, primarily because of the poor donor supply of human fetal neural tissue
      and the incomplete neurobiological understanding of the circuit reconstruction
      required to normalize function in these diseases. So, in PD the progress from
      promising neural transplantation in animal models to proof-of-principle, open
      labeled clinical transplants, to randomized, placebo-controlled studies of neural
      transplantation has not been straightforward. The emergence of previously
      undescribed adverse effects and lack of significant functional advantage in
      recent clinical studies has been disappointing and has served to cast a new, and
      perhaps more realistic, perspective on this treatment approach. In fact, there
      have been calls by some involved in neural transplantation to return to the
      drawing board before pressing on with further clinical trials, and the return to
      basic experimentation. This therefore precipitates the question - is there a
      future for neural transplantation? It is important to remember that there are a
      number of possible explanations for the disappointing results from the recent
      clinical trials in PD, ranging from the mode of transplantation to patient
      selection. Nevertheless, almost irrespective of these reasons for the current
      trial results, there have always been significant practical and ethical problems
      with using human fetal tissue, and so a number of alternative cell sources have
      been investigated. These alternative sources include stem cells, which are
      attractive for cell-based therapies because of their potential ease of isolation,
      propagation and manipulation, and their ability in some cases to migrate to areas
      of pathology and differentiate into specific and appropriate cell types.
      Furthermore, the availability of stem cells derived from non-embryonic sources
      (e.g. adult stem cells derived from the sub-ventricular zone) has removed some of
      the ethical limitations associated with the use of embryonic human tissue. These
      potentially beneficial aspects of stem cells means that there is a future for
      neural transplantation as a means of treating patients with a range of
      neurological disorders, although whether this will ever translate into a truly
      effective, widely available therapy remains unknown.

PMID- 15161333
TI  - Electroporation for gene transfer to skeletal muscles: current status.
AB  - Naked plasmid DNA can be used to introduce genetic material into a variety of
      cell types in vivo. However, such gene transfer and expression is generally very
      low compared with that achieved with viral vectors and so is unsuitable for
      clinical therapeutic application in most cases. This difference in efficiency has
      been substantially reduced by the introduction of in vivo electroporation to
      enhance plasmid delivery to a wide range of tissues including muscle, skin,
      liver, lung, artery, kidney, retina, cornea, spinal cord, brain, synovium, and
      tumors. The precise mechanism of in vivo electroporation is uncertain, but
      appears to involve both electropore formation and an electrophoretic movement of
      the plasmid DNA. Skeletal muscle is a favored target tissue for three reasons:
      there is a pressing need to develop effective therapies for muscular dystrophies;
      skeletal muscle can act as an effective platform for the long-term secretion of
      therapeutic proteins for systemic distribution; and introduction of DNA vaccines
      into skeletal muscle promotes strong humoral and cellular immune responses. All
      of these applications are significantly improved by the application of in vivo
      electroporation. Importantly, the increased efficiency of plasmid delivery
      following electroporation is seen in larger species as well as rodents, in
      contrast to the decreasing efficiencies with increasing body size for simple
      intramuscular injection of naked plasmid DNA. As this electroporation-enhanced
      non-viral gene delivery system works well in larger species and avoids the vector
      specific immune responses associated with recombinant viruses, the prospects for
      clinical application are promising.

PMID- 15161329
TI  - Valdecoxib: a review of its use in the management of osteoarthritis, rheumatoid
      arthritis, dysmenorrhoea and acute pain.
AB  - Valdecoxib is an orally administered, highly selective cyclo-oxygenase (COX)-2
      inhibitor with anti-inflammatory and analgesic properties. In well designed
      trials, valdecoxib demonstrated efficacy versus placebo in patients with
      osteoarthritis (OA), rheumatoid arthritis (RA), primary dysmenorrhoea and
      postoperative pain. Initial results in patients with migraine headache were
      promising. The efficacy of valdecoxib appears dose dependent up to 40 mg/day.
      Valdecoxib 10 mg/day was as effective as naproxen and rofecoxib in improving
      signs and symptoms of OA. The American College of Rheumatology 20% response rate
      was similar in recipients of valdecoxib, naproxen and diclofenac in patients with
      RA. In patients with dysmenorrhoea, valdecoxib 20 or 40 mg up to twice daily
      provided as effective pain relief as naproxen sodium 550 mg twice daily. In acute
      post-surgical pain, single-dose valdecoxib 40 mg had a rapid onset of action,
      provided similar analgesia to oxycodone 10 mg plus paracetamol (acetaminophen)
      1000 mg and provided a longer time to rescue medication than rofecoxib or
      oxycodone/paracetamol after oral surgery. Pre-emptive administration of
      valdecoxib 10-80 mg was particularly effective in dental pain. Valdecoxib had
      opioid-sparing effects after hip or knee arthroplasty and reduced pain after
      laparoscopic cholecystectomy. Valdecoxib is generally well tolerated. The
      incidence of gastroduodenal ulcers was generally lower than with nonselective
      NSAIDs (i.e. NSAIDs not specifically developed as selective COX-2 inhibitors).
      With concomitant aspirin, the ulcer rate in valdecoxib recipients increased
      significantly, but was still lower than that in recipients of aspirin plus
      nonselective NSAIDs. In conclusion, valdecoxib, a COX-2-selective inhibitor, is
      as efficacious in pain relief as nonselective NSAIDs, with better
      gastrointestinal tolerability. It was as effective in RA, OA and primary
      dysmenorrhoea (the approved indications) as nonselective NSAIDs and as effective
      as rofecoxib in RA flare. In acute post-surgical pain, valdecoxib provided
      similar pain relief to oxycodone/paracetamol, had a long duration of action, a
      rapid onset of analgesia and was opioid-sparing. Valdecoxib provides a valuable
      alternative in the treatment of chronic arthritis pain and acute pain.

PMID- 15161334
TI  - Kinase targets and inhibitors for the treatment of airway inflammatory diseases:
      the next generation of drugs for severe asthma and COPD?
AB  - Kinases are believed to play a crucial role in the expression and activation of
      inflammatory mediators in the airway, in T-cell function, and in airway
      remodeling. Important pro-inflammatory transcription factors such as activating
      protein-1 and nuclear factor kappaB, which are activated in airway disease,
      require kinase activation to switch on inflammatory genes, while other kinases
      can regulate mRNA half-life. Selective kinase inhibitors have been developed that
      reduce inflammatory gene expression and some characteristics of disease in animal
      models. Targeting specific kinases that are overexpressed or overactive in
      disease should allow for selective treatment of airway inflammatory diseases.
      Interest in this area has intensified due to the success of the specific Abelson
      murine leukemia viral oncogene homolog tyrosine kinase inhibitor, imatinib
      mesylate, in the treatment of chronic myelogenous leukemia. Encouraging data from
      animal models and primary cells and early phase I and II studies in other
      diseases suggest that inhibitors of p38 mitogen-activated protein kinase and
      inhibitor of kappaB kinase-2 may prove to be useful novel therapies in the
      treatment of severe asthma and chronic obstructive pulmonary disease.

PMID- 15161335
TI  - New drug targets in rheumatoid arthritis: focus on chemokines.
AB  - Rheumatoid arthritis is a chronic inflammatory disease where the synovial tissue
      is characterized by heavy infiltration of leukocytes. Chemokines and chemokine
      receptors play an important role in cell migration and positioning of leukocytes
      within the inflamed rheumatoid synovium. There is now much focus on the specific
      contribution and role of each chemokine and chemokine receptor in the chronic
      inflammatory process in the synovial tissue. Recent evidence indicates that
      interference with the chemokines released from the inflamed synovial cells or the
      chemokine receptors expressed on the cells infiltrating the synovial tissue may
      lead to discovery of new therapeutics for this disease.

PMID- 15161337
TI  - Etanercept: in ankylosing spondylitis.
AB  - Etanercept is a dimeric fusion protein based on the p75 tumor necrosis factor
      (TNF) receptor. It binds to TNFalpha and blocks its biological activity.
      Subcutaneous etanercept is effective in the treatment of rheumatoid arthritis,
      psoriatic arthritis, and polyarticular-course juvenile rheumatoid arthritis. More
      recently, etanercept has shown efficacy in the treatment of adults with
      ankylosing spondylitis. In randomized, double-blind, placebo-controlled trials,
      subcutaneous etanercept 25mg twice weekly for 6-24 weeks significantly reduced
      disease activity in patients with active ankylosing spondylitis. In the largest
      trial, etanercept produced a response rate of 57% compared with 22% for placebo
      after 24 weeks (response was determined via the validated ASAS 20 response
      criteria developed by the Assessments in Ankylosing Spondylitis [ASAS] Working
      Group). Etanercept therapy significantly improved health-related quality of life
      in patients with ankylosing spondylitis compared with placebo. The greatest
      improvements in a 16-week study were seen in the domains of physical functioning,
      physical role, bodily pain, vitality, and social functioning. Etanercept was
      generally well tolerated, with few serious adverse events or treatment
      withdrawals. The most common adverse events were injection-site reactions and
      minor upper respiratory tract infections.

PMID- 15161336
TI  - Development of a reproducible procedure for plasmid DNA encapsulation by red
      blood cell ghosts.
AB  - OBJECTIVE: The binding and encapsulation of [3H] pGL3 luciferase reporter plasmid
      DNA by red blood cell (RBC) ghosts, intended as a vehicle for transfection and
      ultimately for gene therapy, were studied using two methods for DNA compaction.
      METHODS AND RESULTS: In the first approach, DNA was compacted through binding
      electrostatically to poly-L-lysine. Complexes were constructed to have a slight
      negative charge. Experimentally, it was found that a high percentage of binding
      was to the outside of the resealed RBC ghosts. An alternative approach using
      polyethylene glycol6000 at a final concentration of 15% (weight/volume) was used
      to collapse [3H] pGL3 DNA in the presence of 0.025M MgCl2. Addition of the
      reagents, premixed with DNA, to a pelleted suspension of RBC ghosts followed by a
      short incubation and then addition of 1.5 M NaCl to restore tonicity, resulted in
      resealing of the ghosts. Uptake of [3H] pGL3 DNA by the ghosts was approximately
      20% of the input amount of DNA. Further work showed that 60-70% of the DNA was
      inside the resealed ghosts and largely present in the supercoiled form. At no
      stage was any freezing and thawing used. CONCLUSION: Transfection studies have
      demonstrated that pGL3 DNA carrying the luciferase gene is successfully
      transferred from RBC ghosts to recipient HeLa cells in culture under mild fusion
      conditions.

PMID- 15161340
TI  - Spotlight on imatinib mesylate in chronic myeloid leukemia.
AB  - Imatinib mesylate (Gleevec, Glivec) is an orally administered competitive
      inhibitor of the BCR-ABL tyrosine kinase created by the Philadelphia chromosome
      (Ph+) in chronic myeloid leukemia (CML). In patients with newly diagnosed and
      previously untreated (apart from hydroxyurea and/or anagrelide) CML in the
      chronic phase, imatinib mesylate 400 mg/day, compared with interferon-alpha
      (IFNalpha) plus cytarabine, resulted in higher hematologic response (HR) and
      cytogenetic response (CR) rates and fewer patients progressing to the accelerated
      phase or blast crisis in a large comparative trial. Preliminary results indicate
      that, compared with IFNalpha plus cytarabine, imatinib mesylate treatment was
      associated with similar total costs, but resulted in a higher health-related
      quality of life (HR-QOL). Imatinib mesylate was also effective in patients with
      chronic-phase CML refractory to or intolerant of treatment with IFNalpha (as 400
      mg/day) and in those with blast-crisis or accelerated-phase CML (600 mg/day). In
      the latter groups, HR and CR rates were lower than those in patients with chronic
      phase CML. Imatinib mesylate-associated adverse events were common in clinical
      trials, but were mostly mild to moderate in severity. The most frequently
      reported adverse events were superficial edema, nausea, muscle cramps, diarrhea,
      vomiting, and skin rash. Myelosuppression (thrombocytopenia and neutropenia) was
      also reported, especially in patients with advanced disease. In patients with
      previously untreated chronic-phase CML, serious adverse events (both hematologic
      and nonhematologic) were less common with imatinib mesylate than with IFNalpha
      plus cytarabine treatment. CONCLUSION: Imatinib mesylate is a valuable therapy
      for patients with newly diagnosed Ph+ chronic-phase CML. It is better tolerated
      and produces higher HR, CR and freedom from progressive disease rates than
      conventional therapy with IFNalpha plus cytarabine. Preliminary results indicate
      that, compared with IFNalpha plus cytarabine, imatinib mesylate treatment was
      associated with similar total costs, but resulted in a higher HR-QOL. Imatinib
      mesylate is also effective in patients with accelerated-phase and blast-crisis
      CML, and patients with chronic-phase CML who have failed IFNalpha therapy. Given
      its efficacy and generally manageable adverse event profile, imatinib mesylate
      offers an important early treatment option for patients with CML.

PMID- 15161342
TI  - Radiation and noncancer diseases.

PMID- 15161341
TI  - Creation of a stable mammary tumor cell line that maintains fertility-cycle tumor
      biology of the parent tumor.
AB  - A mammary tumor cell line, designated MTCL, was successfully established from a
      mouse primary mammary tumor (MTP). The MTCL cells retain cytokeratin and both
      estrogen receptor (ER) and progesterone receptor (PR) in vitro. In vitro exposure
      of MTCL cells to progesterone causes a decrease in the cellular (3)H-thymidine
      uptake, indicating an inhibition by progesterone on MTCL cellular
      deoxyribonucleic acid synthesis, whereas exposure of the cells to a high dose of
      estrogen (15 pg/ml) for 48 h causes an increase of (3)H-thymidine uptake. We
      inoculated both MTP or MTCL tumor cells into normal cycling female C(3)HeB/FeJ
      mice and demonstrated that the post-resection metastatic recurrence of MTCL
      tumors, like the original MTP tumors, depends on the time of tumor resection
      within the mouse estrous-cycle stage. Both MTCL and MTP tumors have similar
      histological appearances with the exception of less extensive tumor necrosis and
      higher vascularity in MTCL tumors. Equivalent levels of sex hormone receptors (ER
      alpha, ER beta, and PR), epithelial growth hormone receptors (Her2/neu, EGFR1),
      tumor suppressors (BRCA1, P53), and cell apoptosis-relevant protein (bcl-xl) were
      found in these in vivo tumors by immunohistochemistry. Cyclin E protein, however,
      was significantly higher in MTP tumors compared with MTCL tumors. Our results
      indicate that MTCL cells retain many of the biologic features of the original MTP
      primary tumor cells, and to our knowledge, it is the first in vitro cell line
      that has been shown to maintain the estrous-cycle dependence of in vivo cancer
      metastasis.

PMID- 15161344
TI  - Comments on "No lengthening of life span in mice continuously exposed to gamma
      rays at very low dose rates" by S. Tanaka et al. (Radiat. Res. 160, 376-379,
      2003).

PMID- 15161345
TI  - Accumulation, activation and interindividual variation of the epidermal TP53
      protein in response to ionizing radiation in organ cultured human skin.
AB  - In this study, we examined effects of low-dose ionizing radiation on organ
      cultured human foreskin and, in particular, on the epidermis. Diagnostic,
      therapeutic, natural environmental and incidental exposures to moderate to low
      doses of radiation are inevitable and, although information on cultured cells
      continues to accumulate, little is known about the effects of low-dose radiation
      on human tissues. Our hypothesis is that ex vivo organ cultured foreskin is a
      simple and reliable model to study the biochemical effects of low-dose radiation
      exposure on skin. A model such as this will aid in the identification and
      quantification of low-dose radiation-induced changes in proteins in human skin
      and may be useful in the development of a precise, non-invasive, and reliable
      assay of exposure. In this work, several aspects of skin responses to culture
      conditions and radiation were examined. The responses of epidermal TP53 from
      organ cultured skin irradiated in medium with and without serum were found to be
      similar. TP53 levels in organ cultured neonatal foreskin epidermis were then
      examined for baseline TP53 expression. After an initial increase at 4 h, the TP53
      D01 signal returned to low steady-state levels for at least 72 h. Irradiated skin
      samples from different individuals revealed variations in the TP53 D01 signal.
      The dose and temporal response of dermis and epidermis to radiation were examined
      by Western blotting from 0 to 24 h after exposure. After irradiation and
      incubation, the epidermis was removed and assayed by Western blotting and was
      found to have increases in the TP53 D01 epitope and the TP53 phosphoserine 15
      (TP53-S15p) epitope that reached a maximum at about 3 h. In the epidermis, doses
      of 1-5 cGy of radiation were detectable with the TP53 D01, and CDKN1A antibodies
      and doses greater than 10 cGy were detectable with the TP53-S15p antibody. When
      the dermis was compared to epidermis, it was found that dermis had a smaller
      response to radiation and more phosphorylated TP53.

PMID- 15161346
TI  - A multi-port low-fluence alpha-particle irradiator: fabrication, testing and
      benchmark radiobiological studies.
AB  - A new multi-port irradiator, designed to facilitate the study of the effects of
      low fluences of alpha particles on monolayer cultures, has been developed. The
      irradiator consists of four individual planar (241)Am alpha-particle sources that
      are housed inside a helium-filled Lucite chamber. Three of the radioactive
      sources consist of 20 MBq of (241)Am dioxide foil. The fourth source, used to
      produce higher dose rates, has an activity of 500 MBq. The four sources are
      mounted on rotating turntables parallel to their respective 1.5-microm-thick
      Mylar exit windows. A stainless steel honeycomb collimator is placed between the
      four sources and their exit windows by a cantilever attachment to the platform of
      an orbital shaker that moves its table in an orbit of 2 cm. Each exit window is
      equipped with a beam delimiter to optimize the uniformity of the beam and with a
      high-precision electronic shutter. Opening and closing of the shutters is
      controlled with a high-precision timer. Custom-designed stainless steel Mylar
      bottomed culture dishes are placed on an adapter on the shutter. The alpha
      particles that strike the cells have a mean energy of 2.9 MeV. The corresponding
      LET distribution of the particles has a mean value of 132 keV/microm. Clonogenic
      cell survival experiments with AG1522 human fibroblasts indicate that the RBE of
      the alpha particles compared to (137)Cs gamma rays is about 7.6 for this
      biological end point.

PMID- 15161348
TI  - Differential qualitative and temporal changes in the response of the hypothalamus
      pituitary-adrenal axis in rats after localized or total-body irradiation.
AB  - Stress such as exposure to ionizing radiation is able to activate the
      hypothalamus-pituitary-adrenal axis. The present study sought to examine the
      effects of different configurations of a 10-Gy gamma irradiation in rats on the
      hypothalamus-pituitary-adrenal axis to understand the mechanism of negative
      feedback by glucocorticoids induced by ionizing radiation. Specifically, we
      determined adrenocorticotropin and corticosterone levels in plasma as well as
      corticotrophin-releasing factor expression in the paraventricular nucleus of the
      hypothalamus by in situ hybridization from 6 h to 4 days after total-body,
      abdominal or head irradiation. In this study, we found an activation of the
      hypothalamus-pituitary-adrenal axis after radiation exposure. Plasma
      adrenocorticotropin and corticosterone levels were significantly increased after
      total-body and abdominal irradiation 3 days after exposure, in parallel with
      decreased labeling of corticotrophin-releasing factor mRNA in the parvocellular
      region of the paraventricular nucleus of the hypothalamus. Our results suggest
      that ionizing radiation activates the neuroendocrine system to protect the
      organism from the occurrence of radiation-induced inflammation.

PMID- 15161347
TI  - Effects of Pd-bacteriopheophorbide (TOOKAD)-mediated photodynamic therapy on
      canine prostate pretreated with ionizing radiation.
AB  - The aim of this study was to evaluate the effects of photodynamic therapy (PDT)
      using a novel palladium bacteriopherophorbide photosensitizer TOOKAD (WST09) on
      canine prostate that had been pretreated with ionizing radiation. To produce a
      physiological and anatomical environment in canine prostate similar to that in
      patients for whom radiotherapy has failed, canine prostates (n = 4) were exposed
      to ionizing radiation (54 Gy) 5 to 6 months prior to interstitial TOOKAD-mediated
      PDT. Light irradiation (763 nm, 50-200 J/cm at 150 mW/cm from a 1-cm cylindrical
      diffusing fiber) was delivered during intravenous infusion of TOOKAD at 2 mg/kg
      over 10 min. Interstitial measurements of tissue oxygen profile (pO(2)) and of
      local light fluence rate were also measured. The prostates were harvested for
      histological examination 1 week after PDT. The baseline pO(2) of preirradiated
      prostate was in the range 10-44 mmHg. The changes in relative light fluence rate
      during PDT ranged from 12 to 43%. The acute lesions were characterized by
      hemorrhagic necrosis, clearly distinguishable from the radiotherapy-induced pre
      existing fibrosis. The lesion size was correlated with light fluence and
      comparable to that in unirradiated prostate treated with a similar TOOKAD-PDT
      protocol. There was no noticeable damage to the urethra, bladder or adjacent
      colon. The preliminary results obtained from a small number of animals indicate
      that TOOKAD-PDT can effectively ablate prostate pretreated with ionizing
      radiation, and so it may provide an alternative modality for those prostate
      cancer patients for whom radiotherapy has failed.

PMID- 15161349
TI  - Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs.
      II. The RAS/MAPK pathway and phosphorylation of BAD at serine 112.
AB  - Radiation-induced endothelial cell apoptosis is involved in the development of
      many radiation injuries, including radiation-induced skin ulcers. The
      proangiogenic growth factor basic fibroblast growth factor (bFGF, NUDT6) enhances
      endothelial cell survival. In the present study, we set up a model of apoptosis
      in which primary cultured human umbilical vein endothelial cells (HUVECs) were
      irradiated with (60)Co gamma rays to explore the effects of bFGF on radiation
      induced apoptosis of HUVECs and the signaling pathways involved. We found that
      bFGF inhibited radiation-induced apoptosis of HUVECs, and that the effect was
      mediated in part by the RAS/MEK/ MAPK/RSK (p90 ribosomal S6 kinase)/BAD pathway.
      This pathway was activated by exposure of irradiated HUVECs to bFGF, involving
      phosphorylation of FGFR, MEK and p44/42 MAPK. The survival-enhancing effect of
      bFGF was partly inhibited by U0126 and PD98059. The fact that the anti-apoptosis
      effect of bFGF on irradiated HUVECs was not completely abrogated by U0126 and
      PD98059 suggests that other survival signaling pathways may exist. Transfection
      of a dominant-negative form of RSK2 (DN RSK2) partly blocked the anti-apoptosis
      effect of bFGF in irradiated HUVECs. Moreover, we provide evidence for the first
      time that bFGF induced BAD phosphorylation (at serine 112) and CREB (cAMP
      response element-binding protein) activation (phosphorylation at serine 133) in
      gamma-irradiated HUVECs. In our model, inhibition of MAPK signaling-dependent
      phosphorylation of BAD at serine 112 promoted increased association with BCL
      X(L), suggesting that MAPK pathway-dependent serine 112 phosphorylation of BAD is
      critical for the effect of bFGF on cell survival. These results showed that
      RAS/MAPK/BAD pathway participated in the bFGF-induced effect on survival of
      HUVECs exposed to radiation. It is suggested that RAS/ MAPK pathway in tumor
      vascular endothelium could be a potential therapeutic target to enhance the
      efficacy of ionizing radiation.

PMID- 15161350
TI  - Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. I.
      The PI3K/AKT pathway and induction of phosphorylation of BAD.
AB  - Radiation-induced endothelial cell apoptosis is involved in the development of
      many radiation injuries, including radiation-induced skin ulcers. The
      proangiogenic growth factors basic fibroblast growth factor (bFGF, NUDT6) and
      VEGF enhance endothelial cell survival. In the present study, we used primary
      cultured human umbilical vein endothelial cells (HUVECs) irradiated with (60)Co
      gamma rays to explore the effects of bFGF on radiation-induced apoptosis of
      HUVECs and its signaling pathways. We found that bFGF inhibited radiation-induced
      apoptosis of HUVECs, and that the effect was mediated by the PI3K/AKT pathway.
      This pathway was activated by exposure of irradiated HUVECs to bFGF, involving
      phosphorylation of FGFR, PI3K and AKT. The survival-enhancing effect of bFGF was
      abrogated by wortmannin and LY294002. Transfection of a dominant-negative mutant
      of AKT completely blocked the anti-apoptosis effect of bFGF in irradiated HUVECs.
      We also found evidence for the first time that bFGF induced BAD phosphorylation
      in the gamma-irradiated HUVECs. These results showed that the PI3K/AKT pathway
      participated in the bFGF-induced modulation of the survival of irradiated HUVECs.
      Activation of the PI3K/AKT pathway plays an important role in bFGF-induced
      endothelial cell survival in the treatment of radiation-induced skin ulcers.

PMID- 15161351
TI  - UV-radiation-induced internalization of the epidermal growth factor receptor
      requires distinct serine and tyrosine residues in the cytoplasmic carboxy
      terminal domain.
AB  - The mechanism of UV-radiation-induced EGF receptor (EGFR) internalization remains
      to be established. In the present study, we found UV-radiation-mediated
      internalization of the EGFR to be dependent on the cytoplasmic carboxy-terminal
      region. UV radiation was unable to induce internalization of EGFR carboxy
      terminal truncation mutants where all or four of the five major
      autophosphorylation sites were missing (963- and 1028-EGFR, respectively).
      Mutational removal of serine residues 1046, 1047, 1057 and 1142 within the
      carboxy-terminal receptor region was also sufficient to abolish UV-radiation
      induced internalization of the EGFR. Furthermore, the UV-radiation-induced
      internalization was abrogated for an EGFR mutated in tyrosine 1045 (Y1045F), the
      major c-Cbl binding site. However, UV radiation did not induce phosphorylation at
      tyrosine 1045, in contrast to the prominent phosphorylation induced by EGF. Our
      results suggest a mechanism for UV-radiation-induced internalization of EGFR
      involving a conformational change that is dependent on structural elements formed
      by specific serine and tyrosine residues in the carboxy-terminal domain.

PMID- 15161352
TI  - Accumulation of the cell cycle regulators TP53 and CDKN1A (p21) in human
      fibroblasts after exposure to low- and high-LET radiation.
AB  - The accumulation of the cell cycle regulators TP53 and CDKN1A (p21/CIP1/WAF1) was
      investigated after exposure to X rays and carbon ions (170 keV microm(-1)) and
      xenon, bismuth and uranium ions (8900-15,000 keV microm(-1)) in normal human
      fibroblasts. The influence of the overall dose and the LET of these radiation
      types was studied systematically and the kinetics of the cell response was
      followed up to 24 h after exposure. The accumulation of TP53 protein was
      dependent on the dose and the LET, and TP53 levels declined to lower levels for
      all radiation types within 24 h after exposure. CDKN1A levels increased and
      peaked at 3 to 6 h after exposure. The persisting level of this protein at 24 h
      was strongly dependent on the dose and the LET for X rays and carbon ions. The
      exposure to very high-LET ions (8900-15,000 keV microm(-1)) did not lead to a
      further increase in CDKN1A, suggesting a saturation effect for the induction of
      this protein. The cellular effects of elevated CDKN1A after particle irradiation
      are discussed.

PMID- 15161354
TI  - Oxygen dependence of the metabolic activation and cytotoxicity of tirapazamine:
      implications for extravascular transport and activity in tumors.
AB  - The hypoxic cytotoxin tirapazamine (TPZ) is currently in phase III clinical trial
      and appears to have clinical activity. One hypothesis as to why TPZ has been used
      more successfully in the clinic than most other bioreductive drugs is that its
      unusual O(2) dependence allows killing of radioresistant cells at "intermediate"
      O(2) concentrations. We have determined the O(2) dependence of the metabolism of
      TPZ to its reduction product SR 4317, and its cytotoxicity, in stirred
      suspensions of HT29 colon carcinoma cells while monitoring O(2) in solution with
      an Oxylite trade mark probe. The O(2) dependence of the cytotoxicity of TPZ is
      entirely accounted for by its inhibition of the metabolism of TPZ, with a K(O(2))
      value (O(2) concentration for 50% inhibition) of 1.21 +/- 0.09 (SEM) microM. We
      used this experimental O(2) dependence to extend a recent (Hicks et al., Cancer
      Res. 63, 5970-5977, 2003) pharmacokinetic/pharmacodynamic model for the
      cytotoxicity of TPZ in anoxic HT29 multicellular layers to model cell killing in
      tumors. The model indicates that the O(2) dependence of killing by TPZ
      complements that of radiation well during fractionated radiotherapy. It predicts
      that lowering K(O(2)) would decrease killing in radioresistant cells at
      intermediate O(2) concentrations, while higher K(O(2)) values would exacerbate
      metabolic consumption of TPZ and thus further impede its penetration into hypoxic
      regions. Raising K(O(2)) would also increase metabolic activation at
      physiological O(2) concentrations, thereby compromising hypoxic selectivity. We
      conclude that the K(O(2)) value of TPZ is indeed close to the optimum for a
      bioreductive drug of this class (i.e. one that kills only cells in which it is
      reduced).

PMID- 15161355
TI  - Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.
AB  - Space exploration has the potential to yield exciting and significant
      discoveries, but it also brings with it many risks for flight crews. Among the
      less well studied of these are health effects from space radiation, which
      includes the highly charged, energetic particles of elements with high atomic
      numbers that constitute the galactic cosmic rays. In this study, we demonstrated
      that 1 Gy iron ions acutely administered to mice in vivo resulted in highly
      complex chromosome damage. We found that all types of aberrations, including
      dicentrics as well as translocations, insertions and acentric fragments,
      disappear rapidly with time after exposure, probably as a result of the death of
      heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In
      addition, numerous cells have apparently simple exchanges as their only
      aberrations, and these cells appear to survive longer than heavily damaged cells.
      Eight weeks after exposure, the frequency of cells showing cytogenetic damage was
      reduced to less than 20% of the levels evident at 1 week, with little further
      decline apparent over an additional 8 weeks. These results indicate that exposure
      to 1 Gy iron ions produces heavily damaged cells, a small fraction of which
      appear to be capable of surviving for relatively long periods. The health effects
      of exposure to high-LET radiation in humans on prolonged space flights should
      remain a matter of concern.

PMID- 15161353
TI  - Enhancement of radiation sensitivity of human squamous carcinoma cells by histone
      deacetylase inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents with
      potential for disruption of critical cellular processes in cancer cells.
      Transcriptional regulation, differentiation, cell cycle arrest, radiation
      sensitization, and apoptosis have been observed in response to exposure to HDAC
      inhibitors. In the present study, we observed that several potent HDAC
      inhibitors, including trichostatin A, suberoylanilide hydroxamic acid, M344 (an
      analogue of hydroxamic acid), and the cyclic tetrapeptide, depsipeptide
      (FR90228), modulate cellular responses to ionizing radiation in cells of two
      human squamous carcinoma lines (SQ-20B and SCC-35), previously characterized as
      intrinsically resistant to radiation. Also exposure to IC(50) concentrations of
      these inhibitors, radiation sensitivities were enhanced in both cell lines.
      Depsipeptide exhibited the greatest effect on SQ-20B cells, decreasing D(0)
      values from 2.62 Gy to 1.64 Gy. M344 was the most active drug in sensitizing SCC
      35 cells, decreasing D(0) values from 1.91 Gy to 1.21 Gy. The mechanisms
      underlying HDAC inhibitor-induced radiosensitization were further investigated by
      extending trichostatin A studies to assess cell cycle distributions and levels of
      apoptosis. Treatment of SQ-20B cells with radiosensitizing concentrations of
      trichostatin A resulted in cell cycle arrest in G(1) phase (>70%) and inhibition
      of DNA synthesis. Contrary to previous reports, induction of apoptosis was very
      low and caspase 3 and 9 were not activated. Taken together, these results
      implicate G(1) arrest and inhibition of DNA synthesis in the mechanisms
      underlying radiation sensitization by trichostatin A and support the use of HDAC
      inhibitors for targeting radioresistant cancers.

PMID- 15161356
TI  - An association between oxidative stress and radiation-induced lymphomagenesis.
AB  - It is generally thought that reactive oxygen species (ROS) play an important role
      in carcinogenesis. However, direct evidence supporting this idea is still
      lacking. In the present study, we measured ROS in thymocytes at the thymic
      prelymphoma stage in C57BL/6 mice. Mice (n = 20) were irradiated at 1.6 Gy/week
      for 4 consecutive weeks and the levels of ROS were measured 8 to 11 weeks later
      by dehydrorhodamine 123, which accumulated in mitochondria and became fluorescent
      dye upon oxidation. Unirradiated littermates (n = 17) served as controls. Thymic
      prelymphoma cells were diagnosed by the aberrant CD4/CD8 staining profile and
      monoclonal or oligoclonal T-cell receptor gene rearrangement. A significant
      fraction of mice (11/13) bearing thymic prelymphoma cells exhibited elevated
      levels of ROS in thymocytes (P < 0.001). The result is consistent with the
      hypothesis that ROS may play an important role in radiation carcinogenesis.

PMID- 15161357
TI  - Analysis of mortality among Canadian nuclear power industry workers after chronic
      low-dose exposure to ionizing radiation.
AB  - Studies of radiation-associated risks among workers chronically exposed to low
      doses of radiation are important, both to estimate risks directly and to assess
      the adequacy of extrapolations of risk estimates from high-dose studies. This
      paper presents results based on a cohort of 45,468 nuclear power industry workers
      from the Canadian National Dose Registry monitored for more than 1 year for
      chronic low-dose whole-body ionizing radiation exposures sometime between 1957
      and 1994 (mean duration of monitoring = 7.4 years, mean cumulative equivalent
      dose = 13.5 mSv). The excess relative risks for leukemia [excluding chronic
      lymphocytic leukemia (CLL)] and for all solid cancers were 52.5 [95% confidence
      interval (CI): 0.205, 291] and 2.80 (95% CI: -0.038, 7.13) per sievert,
      respectively, both associations having P values close to 0.05. Relative risks by
      dose categories increased monotonically for leukemia excluding CLL but were less
      consistent for all solid cancers combined. Although the point estimates are
      higher than those found in other studies of whole-body irradiation, the
      difference could well be due to chance. Further follow-up of this cohort or the
      combination of results from multiple worker studies will produce more stable
      estimates and thus complement the risk estimates from higher-dose studies.

PMID- 15161358
TI  - Noncancer disease incidence in atomic bomb survivors, 1958-1998.
AB  - We examined the relationships between the incidence of noncancer diseases and
      atomic bomb radiation dose using the longitudinal data for about 10,000 Adult
      Health Study (AHS) participants during 1958-1998. The current report updates the
      analysis we presented in 1993 with 12 additional years of follow-up. In addition
      to the statistically significant positive linear dose-response relationships
      detected previously for the incidence of thyroid disease (P < 0.0001), chronic
      liver disease and cirrhosis (P = 0.001), and uterine myoma (P < 0.00001), we also
      found a significant positive dose response for cataract (P = 0.026), a negative
      linear dose-response relationship for glaucoma (P = 0.025), and significant
      quadratic dose-response relationships for hypertension (P = 0.028) and for
      myocardial infarction among survivors exposed at less than 40 years of age (P =
      0.049). Significant radiation effects for calculus of the kidney and ureter were
      evident for men but not for women (test of heterogeneity by sex: P = 0.007).
      Accounting for smoking and drinking did not alter the results. Radiation effects
      for cataract, glaucoma, hypertension, and calculus of the kidney and ureter in
      men are new findings. These results attest to the need for continued follow-up of
      the aging A-bomb survivors to fully elucidate the effects of radiation exposure
      on the occurrence of noncancer diseases.

PMID- 15161359
TI  - A scientific, moral and diplomatic misstep.

PMID- 15161361
TI  - Renal toxicity after radionuclide therapy.
AB  - During the past 10 years, a variety of radiolabeled monoclonal antibodies,
      antibody fragments, and low-molecular- weight oncophilic peptides have been used
      to deliver radioactivity to target cells for therapeutic purposes. The high and
      persistent localization of several of these radiolabeled molecules in the kidneys
      raised concern about potential renal radiation toxicity compromising therapeutic
      effectiveness. In particular, radiolabeled peptides, such as yttrium-90-labeled
      synthetic somatostatin analogues, have initiated a discussion on the safety
      profiles of the various somatostatin derivatives in recent clinical trials. In
      general, the toxicity risk seems to depend on the characteristics of the
      oncophilic molecule, such as the molecular weight, electric charges and clearance
      pathways as well as the chemical and physical characteristics of the applied
      radionuclide. Encouraging results for the prevention of radiation-induced renal
      damage by radiolabeled peptides have been obtained by co-infusion of positively
      charged amino acids. The available literature on nephrotoxicity after
      radiolabeled peptide therapy is reviewed, and therapeutic options that have
      become available as a result of greater insights into putative pathogenic
      mechanisms are discussed.

PMID- 15161360
TI  - The physical and radiobiological basis of the local effect model: a response to
      the commentary by R. Katz.
AB  - The physical and biological basis of our model to calculate the biological
      effects of charged particles, termed the local effect model (LEM), has recently
      been questioned in a commentary by R. Katz. Major objections were related to the
      definition of the target size and the use of the term cross section. Here we show
      that the objections raised against our approach are unjustified and are largely
      based on serious misunderstandings of the conceptual basis of the local effect
      model. Furthermore, we show that the approach developed by Katz and coworkers
      itself suffers from exactly those deficiencies for which Katz criticizes our
      model. The essential conceptual differences between the two models are discussed
      by means of some illustrative examples, based on a comparison with experimental
      data. For these examples, the predictions of the local effect model are fully
      consistent with the experimental data. In contrast, e.g. for very heavy ions,
      there are significant discrepancies observed for the Katz approach. These
      discrepancies can be attributed to the inadequate definition of the target size
      in this model. Experimental data are thus clearly in favor of the definition of
      the target as used in the local effect model. Agreement with experimental data is
      achieved for protons within the Katz approach but at the cost of questionable
      approximations in combination with the violation of the fundamental physical
      principle of energy conservation.

PMID- 15161362
TI  - Myelodysplasia and radiation.
AB  - Reasons are given why myelodysplasia should be considered in any assessment in
      humans of radiation exposure as an etiological factor for the development of
      leukemia.

PMID- 15161363
TI  - Use of reference gene expression in rat distal colon after radiation exposure: a
      caveat.
AB  - Research on the effects of ionizing radiation exposure includes transcriptome
      studies using real-time reverse transcription polymerase chain reaction (RT-PCR).
      These studies require the use of a reference gene that normalizes for cDNA
      quantity and corrects for transcription between different samples. In this study,
      several criteria are reviewed that allow the choice of a reference gene. With the
      example of five genes selected from the widely used standard housekeeping genes,
      Gapd (glyceraldehyde-3-phosphate dehydrogenase), Hprt (hypoxanthine-guanine
      phosphoribosyl transferase), cyclophilin A, AcRP0 (acidic ribosomal protein P0)
      and 18S, we show that the use of a reference gene without a preliminary study is
      hazardous. We have shown in rat colon after a hemi-body irradiation that
      expression of a gene of interest, the serotonin receptor type 1F (5-HT(1F)), was
      either increased or unchanged, with the result depending on the reference gene
      used. This work has led us to propose the use of two reference genes, a ribosomal
      gene, 18S, and another gene with a level of expression closer to that of the gene
      of interest. The methodology reported here may be applied to other studies of
      gene expression levels to evaluate the effects of experimental treatment on the
      expression of potential reference genes.

PMID- 15161364
TI  - Analysis of low-energy electron track structure in liquid water.
AB  - An implementation is presented of interaction cross sections for non-relativistic
      electron track structure simulations. The model, incorporating liquid-phase cross
      sections for inelastic interactions and improved algorithms for elastic
      scattering, is applied to Monte Carlo simulation of the track structure of low
      energy electrons. Benchmark distributions and mean values are presented for
      several measures of penetration distances that characterize the general physical
      extent of the track structure. The results indicate that, except for the last
      approximately 500 eV of energy loss, electron tracks have a quasi-linear
      character; this suggests that a major part of an electron track may be reasonably
      described by a lineal-energy-like characterization.

PMID- 15161365
TI  - The formation of DNA sugar radicals from photoexcitation of guanine cation
      radicals.
AB  - In this investigation of radical formation and reaction in gamma- irradiated DNA
      and model compounds, we report the conversion of the guanine cation radical (one
      electron oxidized guanine, G(.+)) to the C1' sugar radical and another sugar
      radical at the C3' or C4' position (designated C3'(.)/C4'(.)) by visible and UV
      photolysis. Electron spin resonance (ESR) spectroscopic investigations were
      performed on salmon testes DNA as well as 5'-dGMP, 3'-dGMP, 2'-deoxyguanosine and
      other nucleosides/nucleotides as model systems. DNA samples (25- 150 mg/ml D(2)O)
      were prepared with Tl(3+) or Fe(CN)(3-)(6) as electron scavengers. Upon gamma
      irradiation of such samples at 77 K, the electron-gain path in the DNA is
      strongly suppressed and predominantly G(.+) is found; after UV or visible
      photolysis, the fraction of the C1' sugar radical increases with a concomitant
      reduction in the fraction of G(.+). In model systems, 3'- dGMP(+.) and 5'
      dGMP(+.) were produced by attack of Cl(.-)(2) on the parent nucleotide in 7 M
      LiCl glass. Subsequent visible photolysis of the 3'-dGMP(+.) (77 K) results
      predominantly in formation of C1'(.) whereas photolysis of 5'-dGMP(+.) results
      predominantly in formation of C3'(.)/C4'(.). We propose that sugar radical
      formation is a result of delocalization of the hole in the electronically excited
      base cation radical into the sugar ring, followed by deprotonation at specific
      sites on the sugar.

PMID- 15161366
TI  - Plutonium microdistribution in the lungs of Mayak workers.
AB  - The degree of nonuniform distribution of plutonium in the human lung has not been
      determined; thus current dosimetric models do not account for nonuniform
      irradiation. A better scientific basis is needed for assessing the risk of
      developing radiation-induced disease from inhaled alpha-particle-emitting
      radionuclides. We measured the distribution of plutonium activity in the lung by
      autoradiography and related the activity to specific compartments of the lung.
      The study materials were lung specimens from deceased workers employed by the
      Mayak Production Association. The approach to analyzing these lung samples used
      contemporary stereological sampling and analysis techniques together with
      quantitative alpha-particle autoradiography. For the first time, plutonium
      distribution has been quantified in the human lung. The distribution of long-term
      retained plutonium is nonuniform, and a significant portion of plutonium was
      retained in pulmonary scars. In addition, a large fraction of plutonium was
      present in the parenchyma, where it was retained much longer than was estimated
      previously. The sequestration of plutonium particles in scars would greatly
      reduce the radiation exposure of the critical target cells and tissues for lung
      cancer. Thus the prolonged retention of plutonium in lung scars may not increase
      the dose or risk for lung cancer.

PMID- 15161367
TI  - Effect of administration of lovastatin on the development of late pulmonary
      effects after whole-lung irradiation in a murine model.
AB  - Our group's work on late radiation effects has been governed by the hypothesis
      that the effects observed in normal tissues are a consequence of multicellular
      interactions through a network of mediators. Further, we believe that
      inflammation is a necessary component of this process. We therefore investigated
      whether the recruitment of mononuclear cells, observed during the pneumonitic
      period in the irradiated normal lung, is dependent on the expression of
      chemokines, notably Mcp1. Since statins have been shown to reduce chemokine
      expression and inflammatory cell recruitment, we specifically examined whether
      statins could be used to reduce monocyte recruitment. Mice received 15 Gy whole
      lung irradiation; treated groups were administered lovastatin three times weekly
      starting either immediately or 8 weeks postirradiation. At subsequent intervals,
      animals were killed humanely, and cellular, mRNA and protein analyses were
      undertaken. Statin-treated animals demonstrated a statistically significant
      reduction in both macrophage and lymphocyte populations in the lung compared to
      radiation alone as well as improved rates of survival and decreased collagen
      content. In addition, ELISA measurements showed that radiation-induced increases
      in Mcp1 protein were reduced by statin treatment. Additional experiments are
      needed to assess whether statins offer a potential treatment for the amelioration
      of late effects in breast and lung cancer patients undergoing radiation therapy.

PMID- 15161368
TI  - Combinations of cytokines promote survival of mice and limit acute radiation
      damage in concert with amelioration of vascular damage.
AB  - Recovery from hematopoietic aplasia is a predominant factor in the survival of
      total-body-irradiated mice within 30 days after exposure. However, other
      radiation-induced pathophysiological events have been shown to play a role, among
      which an inflammatory reaction must be considered. In the present study, we
      evaluated the therapeutic potential of a hematopoietic growth factor
      (thrombopoietin, Tpo) and pleiotropic cytokines (Il4 or Il11), used alone or in
      combination, on the survival of mice, hematopoietic reconstitution, inflammatory
      reaction and vascular changes. All treatments including Tpo induced a higher
      level of survival than did treatment with a placebo, with combinations being the
      most efficient. The increased survival could not be explained solely by an
      improved hematopoietic recovery. Treatments with Tpo also reduced the level of
      the chemokine KC in plasma and the level of expression of mRNA for inflammatory
      and coagulation proteins in the lungs of irradiated mice. In addition, radiation-
      induced vascular hyperpermeability was reduced with the use of Tpo. In summary,
      our results show that Tpo may improve survival by limiting vascular leakage,
      which in turn could limit inflammatory reactions and the ensuing tissue damage.

PMID- 15161369
TI  - Chromosome intrachanges and interchanges detected by multicolor banding in
      lymphocytes: searching for clastogen signatures in the human genome.
AB  - Genomic fingerprints of mutagenic agents would have wide applications in the
      field of cancer biology, epidemiology and prevention. The differential spectra of
      chromosomal aberrations induced by different clastogens suggest that ratios of
      specific aberrations can be exploited as biomarkers of carcinogen exposure. We
      have tested this hypothesis using the novel technique of multicolor banding in
      situ hybridization (mBAND) in human peripheral blood lymphocytes exposed in vitro
      to X rays, neutrons, heavy ions, or the restriction endonuclease AluI. In the
      heavy-ion-irradiated cells, we further analyzed aberrations in chromosome 5 using
      multicolor FISH (mFISH). Contrary to the expectations of biophysical models, our
      results do not support the use of the ratios of inter-/intrachromosomal exchanges
      or intra-/interarm intrachanges as fingerprints of exposure to densely ionizing
      radiation. However, our data point to measurable differences in the ratio of
      complex/simple interchanges after exposure to different clastogens. These data
      should be considered in current biophysical models of radiation action in living
      cells.

PMID- 15161370
TI  - The role of Bcl-X(S) in radiation sensitivity.
AB  - Bcl-X(S) is a pro-apoptosis member of the Bcl2 family that has been shown to
      induce cell death and enhance chemosensitivity. We have investigated the effect
      of Bcl-X(S) overexpression on radiation sensitivity. Using a tetracycline
      repressible system, we found that removal of tetracycline for 16 h induced Bcl
      X(S) and reduced the surviving fraction of NIH 3T3 cells to 25%. However,
      radiation sensitivity was not significantly affected by Bcl-X(S) expression; the
      mean inactivation doses for Bcl-X(S) repressed and Bcl-X(S) induced cells were
      2.7 +/- 0.3 and 2.3 +/- 0.1 Gy, respectively. We conclude that Bcl-X(S) induces
      cell death without affecting radiation sensitivity. These results suggest that
      mitochondrial pathways to apoptosis may not have a significant role in survival
      after irradiation.

PMID- 15161371
TI  - Involvement of protein kinase C-related anti-apoptosis signaling in radiation
      induced apoptosis in murine thymic lymphoma(3SBH5) cells.
AB  - Protein kinase C (PKC; also known as PRKC) is known to be an important
      participant in radiation-induced apoptosis. However, its role is not fully
      clarified. Using 3SBH5 cells, which are radiation-sensitive thymic lymphoma
      cells, the involvement and functions of PKC were assessed in radiation- induced
      apoptosis. PMA (phorbol 12-myristate 13-acetate), a PKC activator, inhibited the
      radiation-induced apoptosis in 3SBH5 cells. On the other hand, chelerythrine, a
      PKC inhibitor, potentiated apoptosis. In addition, Go6976, a classical PKC (cPKC)
      inhibitor, which specifically inhibits PKC (alpha and betaI), also promoted
      apoptosis. Interestingly, post-treatment (20 min after irradiation) with Go6976
      had no effect on the radiation-induced apoptosis. These results suggest that cPKC
      is activated early after irradiation for anti-apoptosis signaling and contributes
      to the balance between cell survival and death. Indeed, an increase of cPKC
      activity involving PKC (alpha, betaI and betaII) was observed in the cytosolic
      fraction 3 min after irradiation with 0.5 Gy. However, no translocation of cPKC
      was observed in the cells after irradiation. Our findings indicate that
      activation of cPKC (alpha or beta) soon after irradiation is critical to the
      understanding of the regulation of radiation-induced apoptosis in radiation
      sensitive cells.

PMID- 15161372
TI  - Focus formation of DNA repair proteins in normal and repair-deficient cells
      irradiated with high-LET ions.
AB  - To investigate the repair of clustered lesions within the DNA/chromatin, the
      focus formation and persistence of foci of the phosphorylated histone protein
      H2AX and the repair protein MRE11 were studied in normal cells and in cells
      lacking DNA-PKcs (M059J) or ATM (GM2052D) after irradiation with high-LET
      nitrogen ions or low-LET photons. There was a rapid formation of MRE11 and gamma
      H2AX foci, and 0.5 h after high-LET irradiation, the number of foci in normal
      cells correlated well with the number of particle hits per cell nucleus. After 8
      h of repair, there were significantly more gamma-H2AX foci than MRE11 foci
      remaining in the normal cells, independent of radiation quality. The difficulty
      in repairing clustered breaks was detected as slower rejoining of DSBs (measured
      by DNA fragmentation analysis), as quantification of the amount of gamma-H2AX
      over time, and as a larger fraction of repair foci remaining after 24 h in cells
      irradiated with high- LET ions. These data indicate that clustered lesions are
      repaired by a pathway involving the same proteins that repair sparsely
      distributed breaks. Further, for both low- and high- LET radiation, no reduction
      of the initial number of gamma-H2AX and MRE11 foci was detected in M059J cells up
      to 21 h after irradiation, which was in accordance with a complete absence of DSB
      rejoining in these cells. In the GM2052D cells there was also a higher level of
      foci remaining after 21 h; however, this was not accompanied by unrejoined DSBs,
      indicating that these foci not only represent DSBs but also may be a sign of
      persistent problems even when breaks are rejoined.

PMID- 15161374
TI  - Differential response to radiation of TP53-inactivated cells by overexpression of
      dominant-negative mutant TP53 or HPVE6.
AB  - The inactivation of TP53 by transfection of a dominant- negative mutated TP53
      (MP53.13 cells) was compared with inactivation of TP53 by transfection with the
      HPV E6 gene (RC10.1 cells) with respect to PLD repair, G(1)-phase arrest, and
      induction of color junctions. Functional G(1) arrest was demonstrated in parental
      (RKO) cells with wild-type TP53, while in RC10.1 cells the G(1) arrest was
      eliminated. In MP53.13 cells an intermediate G(1) arrest was found. Functionality
      of endogenous TP53 was confirmed in RKO and MP53.13 cells by accumulation of TP53
      protein and its downstream target CDKN1A (p21). Radiation survival of MP53.13
      cells was higher than that of RKO cells, and PLD repair was found in RKO cells
      and MP53.13 cells but not in RC10.1 cells. Both with and without irradiation, the
      number of color junctions was 50 to 80% higher in MP53.13 cells than in RKO and
      RC10.1 cells. In the MP53.13 cells, the genetic instability appears to lead to
      more aberrations and to radioresistance. In spite of the presence of an excess of
      mutated TP53, wild- type TP53 functions appear to be affected only partly or not
      at all.

PMID- 15161373
TI  - Repair of potentially lethal damage does not depend on functional TP53 in human
      glioblastoma cells.
AB  - The functionality of G(1)-phase arrest was investigated in relation to repair of
      potentially lethal damage (PLD) in human glioblastoma Gli-06 cells. Confluent
      cultures were irradiated and plated for clonogenic survival either immediately or
      24 h after gamma irradiation. Bivariate flow cytometry was performed to assess
      the distribution over the cell cycle. Levels of TP53 and CDKN1A protein were
      assessed with Western blotting and levels of CDKN1A mRNA with RT-PCR. Confluence
      significantly reduced the number of proliferating cells. Marked PLD repair was
      found in the absence of an intact G(1) arrest. No accumulation of TP53 was
      observed, and the protein was smaller than the wild-type TP53 of RKO cells. No
      increased expression of CDKN1A at the mRNA or protein levels was found in Gli-06
      cells. The TP53 of Gli-06 cells was unable to transactivate the CDKN1A gene. From
      this study, it is evident that PLD repair may be present without a functional
      TP53 or G(1) arrest.

PMID- 15161375
TI  - Changes in gene expression associated with stable drug and radiation resistance
      in small cell lung cancer cells are similar to those caused by a single X-ray
      dose.
AB  - Small cell lung cancer (SCLC) initially responds well to chemotherapy and
      fractionated radiotherapy, but resistance to these treatments eventually develops
      in the vast majority of cases. To understand how resistance develops in the H69
      SCLC cell line, we compared the changes in gene expression associated with 37.5
      Gy fractionated X-ray treatment that produced the stable radiation- and drug
      resistant H69/R38 cell subline to the changes associated with a single 4- or 8-Gy
      X-ray treatment. Gene expression was determined by suppression subtractive
      hybridization combined with Northern blot analysis and two-dimensional (2D)
      protein electrophoresis. Stable radiation and drug resistance was associated with
      coordinate changes in the expression of genes of the cytoskeleton, protein
      synthesis, cell cycle, redox/stress and metabolic pathways. The pattern of these
      changes was remarkably similar to the changes seen 24 h after a single X-ray
      treatment of the H69 cells but differed from the changes in expression associated
      with a single X-ray treatment of the resistant H69/ R38 cells. Stable radiation
      and drug resistance may be caused by the constitutive expression of those genes
      transiently expressed by sensitive cells in response to a single X-ray dose. The
      repeated treatments received during fractionated irradiation may promote the
      change from a transient to a constitutive pattern of gene expression.

PMID- 15161376
TI  - Dynamics of balancing space and time in memory: tau and kappa effects revisited.
AB  - In 3 experiments, the authors studied the organization of spatiotemporal
      information in memory. Stimuli consisted of configurations of dots, presented
      sequentially. The stimuli were either proportional, with interdot distances
      corresponding to interdot durations, or not proportional, with interdol distances
      not corresponding to interdot durations. After a learning phase, participants
      reproduced the spatial (Experiment 1), temporal (Experiment 2), or spatial and
      temporal (Experiment 3) characteristics of the target 60 times in succession. In
      the nonproportional conditions, effects of variable interdot durations or
      distances on the reproduction of, respectively, constant distances (tau effect)
      or durations (kappa effect) were observed, whereas no such effects were observed
      when variable distances or durations were to be produced. Tau and kappa effects
      influenced the accuracy but not the variability of responses. The results are
      discussed in light of the distinction between properties of the stabilized mental
      image and the process of stabilization.

PMID- 15161377
TI  - When is the ball going to hit the ground? Duration estimates, eye movements, and
      mental imagery of object motion.
AB  - Performance in 2 versions of a computer-animated task was compared. Participants
      either indicated the time of arrival of a target that rolled off a horizontal
      surface and fell--hidden from view--onto a landing point (production task) or
      judged flight time on a rating scale (judgment task). As predicted, performance
      was significantly better in the production task (Experiment 1), in which imagery
      of object motion probably replaced reasoning processes. Participants who
      exhibited eye movements suggesting mental tracking performed particularly well in
      the production task (Experiment 2). There was, however, no decrement in
      performance when participants were asked to fixate the point where the target
      disappeared. For motion duration estimations, eye movements seem to be only a by
      product of mental tracking.

PMID- 15161378
TI  - Lexical influences in audiovisual speech perception.
AB  - Phoneme identification with audiovisually discrepant stimuli is influenced hy
      information in the visual signal (the McGurk effect). Additionally, lexical
      status affects identification of auditorily presented phonemes. The present study
      tested for lexical influences on the McGurk effect. Participants identified
      phonemes in audiovisually discrepant stimuli in which lexical status of the
      auditory component and of a visually influenced percept was independently varied.
      Visually influenced (McGurk) responses were more frequent when they formed a word
      and when the auditory signal was a nonword (Experiment 1). Lexical effects were
      larger for slow than for fast responses (Experiment 2), as with auditory speech,
      and were replicated with stimuli matched on physical properties (Experiment 3).
      These results are consistent with models in which lexical processing of speech is
      modality independent.

PMID- 15161379
TI  - Visual salience in the change detection paradigm: the special role of object
      onset.
AB  - The relative efficacy with which appearance of a new object orients visual
      attention was investigated. At issue is whether the visual system treats onset as
      being of particular importance or only 1 of a number of stimulus events equally
      likely to summon attention. Using the 1-shot change detection paradigm, the
      authors compared detectability of new objects with changes occurring at already
      present objects--luminance change, color change, and object offset. Results
      showed that appearance of a new object was less susceptible to change blindness
      than changes that old objects could undergo. The authors also investigated
      whether it is onset per se that leads to enhanced detectability or onset of an
      object representation. Results showed that the onset advantage was eliminated for
      onsets that did not correspond with the appearance of a new object. These
      findings suggest that the visual system is particularly sensitive to the onset of
      a new object.

PMID- 15161380
TI  - Pictorial and conceptual representation of glimpsed pictures.
AB  - Pictures seen in a rapid sequence are remembered briefly, but most are forgotten
      within a few seconds (M. C. Potter. A. Staub, J. Rado. & D. H. O'Connor. 2002).
      The authors investigated the pictorial and conceptual components of this fleeting
      memory by presenting 5 pictured scenes and immediately testing recognition of
      verbal titles (e.g., people at a table) or recognition of the pictures
      themselves. Recognition declined during testing, but initial performance was
      higher and the decline steeper when pictures were tested. A final experiment
      included test decoy pictures that were conceptually similar to but visually
      distinct from the original pictures. Yeses to decoys were higher than yeses to
      other distractors. Fleeting memory for glimpsed pictures has a strong conceptual
      component (conceptual short-term memory), but there is additional highly volatile
      pictorial memory (pictorial short-term memory) that is not tapped hy a gist title
      or decoy picture.

PMID- 15161381
TI  - Do muscles matter for coordinated action?
AB  - This article investigates coordination stability when 2 fingers of each hand
      periodically tap together. The main question concerns the functional origin of
      the symmetry tendency, which has widely been conceived as a bias toward
      coactivation of homologous fingers and homologous muscular portions. In
      Experiment 1, the symmetry tendency was independent of finger combination. In
      Experiment 2, virtually identical stability characteristics were revealed under
      full vision and no vision. In Experiment 3, symmetrical and parallel visual
      labels on the fingers neither stabilized nor destabilized symmetrical and
      parallel tapping patterns. In Experiment 4, in which the relative position of the
      hands was varied, it revealed that the observed stability characteristics are to
      be defined in a hand-centered reference frame. Because the symmetry tendency was
      always independent of finger combination, the authors suggest that it is not a
      bias toward coactivation of homologous muscle portions but instead originates on
      a more abstract, functional level.

PMID- 15161382
TI  - Visual grouping by motion precedes the relative localization between moving and
      flashed stimuli.
AB  - A flashed stimulus is perceived as spatially lagging behind a moving stimulus
      when they are spatially aligned. When several elements are perceptually grouped
      into a unitary moving object, a flash presented at the leading edge of the moving
      stimulus suffers a larger spatial lag than a flash presented at the trailing edge
      (K. Watanabe. R. Nijhawan. B. Khurana, & S. Shimojo. 2001). By manipulation of
      the flash onset relative to the motion onset, the present study investigated the
      order of perceptual operations of visual motion grouping and relative visual
      localization. It was found that the asymmetric mislocalization was observed
      irrespective of physical and/or perceptual temporal order between the motion and
      flash onsets. Thus, grouping by motion must be completed to define the leading
      trailing relation in a moving object before the visual system explicitly
      represents the relative positions of moving and flashed stimuli.

PMID- 15161383
TI  - Temporal ventriloquism: sound modulates the flash-lag effect.
AB  - A sound presented in close temporal proximity to a visual stimulus can alter the
      perceived temporal dimensions of the visual stimulus (temporal ventriloquism). In
      this article, the authors demonstrate temporal ventriloquism in the flash-lag
      effect (FLE), a visual illusion in which a flash appears to lag relative to a
      moving object. In Experiment 1, the magnitude and the variability of the FLE were
      reduced, relative to a silent condition, when a noise burst was synchronized with
      the flash. In Experiment 2, the sound was presented before, at, or after the
      flash (+/- approximately 100 ms), and the size of the FLE varied linearly with
      the delay of the sound. These findings demonstrate that an isolated sound can
      sharpen the temporal boundaries of a flash and attract its temporal occurrence.

PMID- 15161384
TI  - Constructing visual representations of natural scenes: the roles of short- and
      long-term visual memory.
AB  - A "follow-the-dot" method was used to investigate the visual memory systems
      supporting accumulation of object information in natural scenes. Participants
      fixated a series of objects in each scene, following a dot cue from object to
      object. Memory for the visual form of a target object was then tested. Object
      memory was consistently superior for the two most recently fixated objects, a
      recency advantage indicating a visual short-term memory component to scene
      representation. In addition, objects examined earlier were remembered at rates
      well above chance, with no evidence of further forgetting when 10 objects
      intervened between target examination and test and only modest forgetting with
      402 intervening objects. This robust prerecency performance indicates a visual
      long-term memory component to scene representation.

PMID- 15161385
TI  - The relationship between inhibition of return and saccade trajectory deviations.
AB  - After presentation of a peripheral cue, a subsequent saccade to the cued location
      is delayed (inhibition of return: IOR). Furthermore, saccades typically deviate
      away from the cued location. The present study examined the relationship between
      these inhibitory effects. IOR and saccade trajectory deviations were found after
      central (endogenous) and peripheral (exogenous) cuing of attention, and both
      effects were larger with an onset cue than with a color singleton cue. However, a
      dissociation in time course was found between IOR and saccade trajectory
      deviations. Saccade trajectory deviations occurred at short delays between the
      cue and the saccade, but IOR was found at longer delays. A model is proposed in
      which IOR is caused by inhibition applied to a preoculomotor attentional map,
      whereas saccade trajectory deviations are caused by inhibition applied to the
      saccade map, in which the final stage of oculomotor programming takes place.

PMID- 15161386
TI  - Automatic keypress activation in skilled typing.
AB  - The assumption that letters automatically activate corresponding keypresses in
      skilled typing was investigated. Participants responded to the color of letters
      (congruent condition: responding finger was the one usually used to type the
      letter). Participants skilled in typing showed a congruency effect: unskilled
      participants did not (Experiment 1). The automatic activation included
      characteristics of the movement usually performed to type the letters (Experiment
      2). Responding with crossed hands on an external response device (Experiment 3)
      provided evidence for effector-dependent representations only, whereas responding
      on a keyhoard (Experiment 4) resulted in evidence for effector-dependent and
      spatial representations. Thus, motoric skill proficiency is accompanied by
      automatic activation processes that probably contribute to high performance
      levels.

PMID- 15161387
TI  - The costs of changing the representation of action: response repetition and
      response-response compatibility in dual tasks.
AB  - In 5 experiments, the authors investigated the costs associated with repeating
      the same or a similar response in a dual-task setting. Using a psychological
      refractory period paradigm, they obtained response-repetition costs when the
      cognitive representation of a specific response (i.e., the category-response
      mapping) changed (Experiment 1) but benefits when it did not change (Experiment
      2). The analogous pattern of results was found for conceptually similar (i.e.
      compatible) responses. Response-response compatibility costs occurred when the
      cognitive representations of the compatible responses were different (Experiments
      3A & 3B), but compatibility benefits occurred when they were the same (Experiment
      4). The authors interpret the costs of repeating an identical or compatible
      response in terms of a general mechanism of action selection that involves coding
      the task-specific meaning of a response.

PMID- 15161388
TI  - Effects of familiarity on the perceptual integrality of the identity and
      expression of faces: the parallel-route hypothesis revisited.
AB  - The effects of familiarity on selective attention for the identity and expression
      of faces were tested using Garner's speeded-classification task. In 2
      experiments, participants classified expression (or identity) of familiar and
      unfamiliar faces while the irrelevant dimension of identity (or expression) was
      either held constant (baseline condition) or varied randomly (filtering
      condition). Selective attention was measured by the difference in performance
      between these 2 conditions. Failure of selective attention was larger for
      familiar than for unfamiliar faces. In addition, failure of selective attention
      was found both for identity and for expression judgments. These findings show
      that familiarity increases (he perceptual integrality between identity and
      expression, and they question previous studies arguing that identity judgments
      are always resistant to irrelevant variations in expression. The authors suggest
      that the systems processing identity and expression are interconnected in that
      facial identity serves as a reference from which expressions can be more easily
      derived.

PMID- 15161389
TI  - Capturing attention when attention blinks.
AB  - Four experiments addressed the question of whether attention may be captured when
      the visual system is in the midst of an attentional blink (AB). Participants
      identified 2 target letters embedded among distractor letters in a rapid serial
      visual presentation sequence. In some trials, a square frame was inserted between
      the targets; as the only geometric object in the sequence, it constituted a
      singleton. Capture effects obtained when the AB was most severe and when it was
      over were compared. There were 3 main results. First, capture occurred even when
      the AB was crippling, suggesting that a singleton exogenously engaged attention
      even when processing of a previous target was continuing apace. Second, when the
      singleton contained the key target feature, capture effects were clearly
      manifest. Third, even when the singleton did not possess the key target feature,
      it still succeeded in capturing attention, although the effects were both feeble
      and fleeting.

PMID- 15161390
TI  - Blink and shrink: the effect of the attentional blink on spatial processing.
AB  - The detection or discrimination of the second of 2 targets in a rapid serial
      visual presentation (RSVP) task is often temporarily impaired-a phenomenon termed
      the attentional blink. This study demonstrated that the attentional blink also
      affects localization performance. Spatial cues pointed out the possible target
      positions in a subsequent visual search display. When cues were presented inside
      an attentional blink (as induced by an RSVP task), the observers' capacity to use
      them was reduced. This effect was not due to attention being highly focused, to
      general task switching costs, or to complete unawareness of the cues. Instead,
      the blink induced a systematic localization bias toward the fovea, reflecting
      what appears to be spatial compression.

PMID- 15161391
TI  - On doing two things at once: IV. Necessary and sufficient conditions: Rejoinder
      to Lien, Proctor, and Ruthruff (2003).
AB  - Four publications have demonstrated perfect timesharing of 1 simultaneous
      decisions. In all of these, (a). subjects were motivated to respond as quickly as
      possible, and with 1 exception that involved unusually extensive practice (E.
      Hazeltine, D. Teague, & R. B. Ivry, 2002, Experiment 4), (b). at least 1 of the 2
      tasks was characterized by ideomotor (IM) compatibility, meaning that each task
      stimulus incorporated a component of the sensory feedback from its required
      response. Conclusions justified by these reports are that (a). the use of speed
      stress instructions is necessary for perfect timesharing of 2 simultaneous
      decision tasks: (b). when both tasks are IM compatible, perfect timesharing
      requires little or no practice: (c). extensive practice is needed to achieve
      perfect timesharing when only 1 of the 2 tasks is IM compatible: and (d). very
      large amounts of practice can yield perfect timesharing of 2 decision tasks when
      neither is IM compatible.

PMID- 15161392
TI  - Reducing the influence of extrapersonal associations on the Implicit Association
      Test: personalizing the IAT.
AB  - The authors argue that the Implicit Association Test (IAT; A.G. Greenwald, D.E.
      McGhee, & J.L.K. Schwartz, 1998) can be contaminated by associations that do not
      contribute to one's evaluation of an attitude object and thus do not become
      activated when one encounters the object but that are nevertheless available in
      memory. The authors propose a variant of the IAT that reduces the contamination
      of these "extrapersonal associations." Consistent with the notion that the
      traditional version of the IAT is affected by society's negative portrayal of
      minority groups, the "personalized" IAT revealed relatively less racial prejudice
      among Whites in Experiments 1 and 2. In Experiments 3 and 4, the personalized IAT
      correlated more strongly with explicit measures of attitudes and behavioral
      intentions than did the traditional IAT. The feasibility of disentangling
      personal and extrapersonal associations is discussed.

PMID- 15161393
TI  - Encoding under trust and distrust: the spontaneous activation of incongruent
      cognitions.
AB  - Past studies of strategic thinking have shown that the encoding of the message
      information becomes more complex under distrust. Receivers process the
      information as if they are trying to protect themselves from being misled by
      testing alternative potential interpretations. The present study investigates the
      possibility that when people are mistrustful they spontaneously activate
      associations that are incongruent with the given message. Findings from 3
      experiments suggest that, even when the distrust is unrelated in any meaningful
      way to the message and even when receivers are unable to prepare a strategic
      response, the cognitive system reacts to distrust by automatically inducing the
      consideration of incongruent associations--it seems designed to ask, "and what if
      the information were false?" The theoretical implications of the results for
      theories of social perception and persuasion are discussed.

PMID- 15161394
TI  - Distinction bias: misprediction and mischoice due to joint evaluation.
AB  - This research identifies a new source of failure to make accurate affective
      predictions or to make experientially optimal choices. When people make
      predictions or choices, they are often in the joint evaluation (JE) mode; when
      people actually experience an event, they are often in the single evaluation (SE)
      mode. The "utility function" of an attribute can vary systematically between SE
      and JE. When people in JE make predictions or choices for events to be
      experienced in SE, they often resort to their JE preferences rather than their SE
      preferences and overpredict the difference that different values of an attribute
      (e.g., different salaries) will make to their happiness in SE. This
      overprediction is referred to as the distinction bias. The present research also
      specifies when the distinction bias occurs and when it does not. This research
      contributes to literatures on experienced utility, affective forecasting, and
      happiness.

PMID- 15161395
TI  - On the importance of cognitive evaluation as a determinant of interpersonal
      attraction.
AB  - Three studies examined a model of attraction in which the cognitive evaluation of
      the target individual was the primary determinant of interpersonal attraction. In
      Study 1, the cognitive evaluation of the target individual mediated the influence
      of attitude similarity on interpersonal attraction. In Study 2, a path analysis
      revealed significant indirect effects of (a) similarity on cognitive evaluation
      via the valence of information implied by attitudes and (b) the valence of
      information implied by attitudes on attraction via cognitive evaluation of the
      target. Study 3 provided empirical and theoretical support for the uniqueness of
      interpersonal attraction from cognitive evaluation. The implications of these
      data for existing attraction theory are discussed, and a new model of
      interpersonal attraction is described.

PMID- 15161397
TI  - Positive expectations in the early years of marriage: should couples expect the
      best or brace for the worst?
AB  - The current study examined whether the effects of positive expectations on
      changes in marital satisfaction over the first 4 years of marriage were moderated
      by the nature of spouses' interaction behaviors and relationship attributions.
      Consistent with predictions, when spouses' skills were most positive, positive
      expectations predicted more stable satisfaction over time whereas less positive
      expectations predicted steeper declines. Alternatively, when spouses' skills were
      most negative, positive expectations predicted steeper declines in satisfaction
      over time whereas less positive expectations predicted more stable satisfaction.
      Thus, in contrast to the idea that expectations in the early years of marriage
      exert main effects on satisfaction, the current findings suggest that the effects
      of expectations interact with the skills partners bring to their relationships.

PMID- 15161396
TI  - Bad but bold: Ambivalent attitudes toward men predict gender inequality in 16
      nations.
AB  - A 16-nation study involving 8,360 participants revealed that hostile and
      benevolent attitudes toward men, assessed by the Ambivalence Toward Men Inventory
      (P. Click & S.T. Fiske, 1999), were (a) reliably measured across cultures, (b)
      positively correlated (for men and women, within samples and across nations) with
      each other and with hostile and benevolent sexism toward women (Ambivalent Sexism
      Inventory, P. Click & S.T. Fiske, 1996), and (c) negatively correlated with
      gender equality in cross-national comparisons. Stereotype measures indicated that
      men were viewed as having less positively valenced but more powerful traits than
      women. The authors argue that hostile as well as benevolent attitudes toward men
      reflect and support gender inequality by characterizing men as being designed for
      dominance.

PMID- 15161398
TI  - Parents' personality and infants' temperament as contributors to their emerging
      relationship.
AB  - The authors examined the contributions of infant's temperament and parent's
      personality to their relationship. In Study 1, 102 infants, mothers, and fathers
      were studied when infants were 7 months; in Study 2, 112 infants and mothers were
      followed from 9 to 45 months. Infants' temperament (joy, fear, anger, and
      attention) was observed in standard temperament paradigms. Parents' personality
      measures encompassed the Big Five traits and Empathy in Study 1 and Mistrust,
      Manipulativeness, Aggression, Dependency, Entitlement, and Workaholism in Study
      2. Parent-child relationship (shared positive affect and parental responsiveness
      in Studies 1 and 2 and parental tracking of the infant in Study 1) was observed
      in naturalistic contexts. In Study 1, mothers' Neuroticism, Empathy, and
      Conscientiousness and fathers' Agreeableness, Openness, and Extraversion related
      to the relationship with the infants. All measures of infant temperament also
      related to the emerging relationship. In Study 2, maternal Mistrust,
      Manipulativeness, Dependency, and Workaholism predicted the relationship with the
      child.

PMID- 15161399
TI  - Intelligence and maturity: meta-analytic evidence for the incremental and
      discriminant validity of Loevinger's measure of ego development.
AB  - This review examined whether Loevinger's measure of personality (ego) development
      is equivalent to the measurement of intelligence. The authors conducted a meta
      analysis of 52 correlations between ego level scores and intelligence test scores
      (retrieved from 42 studies involving 5,648 participants). The weighted average
      correlation between ego level and intelligence ranged from.20 to.34, depending on
      the intellectual ability assessed (e.g., verbal intelligence). Adjusting for
      measurement unreliability increased these values only minimally. The authors also
      reviewed 16 studies that examined the association between ego level and various
      criterion variables (e.g., aggressive behavior) after statistically controlling
      for the effects of intelligence. Ninety-four percent of the tests revealed
      significant relations between ego level and criterion variables after controlling
      for intelligence, indicating that ego development and intelligence are not
      interchangeable constructs. These findings do not support recent speculations
      concerning the limited value of stage models of maturity, social development, and
      moral reasoning.

PMID- 15161401
TI  - Effects of interactional justice on egocentric bias in resource allocation
      decisions.
AB  - Three studies demonstrated that interactional justice was able to attenuate
      egocentric bias, i.e., the tendency to regard a larger share for oneself as fair.
      Study 1, an experimental study of negotiation, showed that fair interpersonal
      treatment led to a smaller egocentric bias, quicker settlements, and fewer
      stalemates. Study 2 showed that fair treatment was related to a smaller
      egocentric bias in a real-life context. University students were more willing to
      accept a higher tuition fee and less willing to cut the salary of their teachers
      if the interpersonal treatment received from the teachers was more positive.
      Study 3 showed experimentally that in support of fairness heuristic theory, when
      the fair interpersonal treatment received could be attributed externally, its
      attenuating effect on the egocentric bias disappeared.

PMID- 15161400
TI  - Organizational justice and stress: the mediating role of work-family conflict.
AB  - This study examined the relationship between organizational justice and stress
      and whether work-family conflict was a mediator of the relationship.
      Distributive, procedural, interpersonal, and informational injustice were cast as
      stressors to explore their relationships with the stress levels of 174 faculty
      members employed at 23 U.S. universities. The results revealed that procedural
      and interpersonal justice had the strongest relationships with stress, and that
      these effects were mediated by work-family conflict. The presence of justice
      seemed to allow participants to better manage the interface of their work and
      family lives, which was associated with lower stress levels. These results were
      observed even when controlling for job satisfaction and the presence of
      organizational work-family policies.

PMID- 15161402
TI  - Penalties for success: reactions to women who succeed at male gender-typed tasks.
AB  - A total of 242 subjects participated in 3 experimental studies investigating
      reactions to a woman's success in a male gender-typed job. Results strongly
      supported the authors' hypotheses, indicating that (a) when women are
      acknowledged to have been successful, they are less liked and more personally
      derogated than equivalently successful men (Studies 1 and 2); (b) these negative
      reactions occur only when the success is in an arena that is distinctly male in
      character (Study 2); and (c) being disliked can have career-affecting outcomes,
      both for overall evaluation and for recommendations concerning organizational
      reward allocation (Study 3). These results were taken to support the idea that
      gender stereotypes can prompt bias in evaluative judgments of women even when
      these women have proved themselves to be successful and demonstrated their
      competence. The distinction between prescriptive and descriptive aspects of
      gender stereotypes is considered, as well as the implications of prescriptive
      gender norms for women in work settings.

PMID- 15161403
TI  - The effect of physical height on workplace success and income: preliminary test
      of a theoretical model.
AB  - In this article, the authors propose a theoretical model of the relationship
      between physical height and career success. We then test several linkages in the
      model based on a meta-analysis of the literature, with results indicating that
      physical height is significantly related to measures of social esteem (rho =.41),
      leader emergence (rho =.24), and performance (rho =.18). Height was somewhat more
      strongly related to success for men (rho =.29) than for women (rho =.21),
      although this difference was not significant. Finally, given that almost no
      research has examined the relationship between individuals' physical height and
      their incomes, we present four large-sample studies (total N = 8,590) showing
      that height is positively related to income (beta =.26) after controlling for
      sex, age, and weight. Overall, this article presents the most comprehensive
      analysis of the relationship of height to workplace success to date, and the
      results suggest that tall individuals have advantages in several important
      aspects of their careers and organizational lives.

PMID- 15161404
TI  - Stressful work, psychological job strain, and turnover: a 2-year prospective
      cohort study of truck drivers.
AB  - Based on a model that combines existing organizational stress theory and job
      transition theory, this 2-year longitudinal study examined antecedents and
      consequences of turnover among Dutch truck drivers. For this purpose, self
      reported data on stressful work (job demands and control), psychological strain
      (need for recovery after work and fatigue), and turnover were obtained from 820
      drivers in 1998 and 2000. In agreement with the model, the results showed that
      strain mediates the influence of stressful work on voluntary turnover. Also in
      conformity with the model, job movement to any job outside the trucking industry
      (i.e., interoccupational turnover) resulted in a larger strain reduction as
      compared to job movement within the trucking industry (intraoccupational
      turnover). Finally, strain was found to stimulate interoccupational turnover more
      strongly than it stimulated intraoccupational turnover. These findings provide a
      thorough validation of existing turnover theory and give new insights into the
      turnover (decision) process.

PMID- 15161405
TI  - Moderators of the relationships between coworkers' organizational citizenship
      behavior and fellow employees' attitudes.
AB  - The authors developed and tested the prediction that the relationship hetween
      coworkers' organizational citizenship behaviors (OCBs) and fellow employees'
      attitudes depends on the supervisors' abusiveness. Results of a longitudinal
      study using data collected from 173 supervised employees at 2 points in time
      (separated by 7 months) suggested that coworkers' OCB was positively related to
      fellow employees' job satisfaction and affective commitment when abusive
      supervision was low. However, when abusive supervision was high, coworkers' OCB
      was negatively related to job satisfaction and was unrelated to organizational
      commitment. The results of a 2nd study were consistent with the idea that the
      attributions employees make for their coworkers' OCB explains the moderating
      effect of abusive supervision on the relationship between coworkers' OCB and job
      satisfaction.

PMID- 15161406
TI  - Understanding customer reactions to brokered ultimatums: applying negotiation and
      justice theory.
AB  - There has been little research examining customer reactions to brokered ultimatum
      game (BUG) contexts (i.e. exchanges in which 1 party offers an ultimatum price
      for a resource through an intermediary, and the ultimatum offer is accepted or
      rejected by the other party). In this study, the authors incorporated rational
      decision-making theory and justice theory to examine how customers' bids,
      recommendations, and repatronage behavior are affected by characteristics of BUG
      contexts (changing from an ultimatum to negotiation transaction, response
      timeliness, and offer acceptance or rejection). Results indicated that customers
      attempt to be economically efficient with their bidding behavior. However,
      negotiation structures, long waits for a response, and rejected bids create
      injustice perceptions (particularly informational and distributive injustice),
      negatively influencing customers' recommendations to others and their
      repatronage. The authors then discuss the practical and theoretical implications
      of their results.

PMID- 15161407
TI  - The construct and criterion validity of emotional intelligence and its potential
      utility for management studies.
AB  - In this study, the authors reviewed the definition of emotional intelligence (EI)
      and argued that El is conceptually distinct from personality. In Study 1, the
      authors showed that EI was related to yet distinct from personality dimensions
      and that it had incremental predictive power on life satisfaction. The authors
      examined the construct validity of self-reports and others' ratings of EI using
      two samples in Study 2. In a student sample, parents' ratings explained
      additional variance in the students' life satisfaction and feelings of
      powerlessness after controlling for the Big Five personality dimensions. In the
      work sample, peer ratings were found to be significant predictors of job
      performance ratings provided by supervisors after controlling for the Big Five
      personality dimensions. Other implications for future research on EI are
      discussed.

PMID- 15161408
TI  - Examining the effects of differential item (functioning and differential) test
      functioning on selection decisions: when are statistically significant effects
      practically important?
AB  - Item response theory differential test functioning (DTP) methods are often used
      to address issues in personnel selection, but the results are frequently
      difficult to interpret because statistically significant findings may have little
      practical importance. In this article, the authors proposed 2 effect size
      measures for DTP. One related DTP to mean raw score differences across groups:
      the other related DTP to the 4/5th rule for adverse impact at successive cut
      scores. The effects of DTP were examined in the context of personality
      assessment, professional licensure, and college admissions. Overall, the result
      indicated that although many items exhibited bias in analyses of the large
      samples, the net magnitudes of effect on potential selection decisions were
      nugatory.

PMID- 15161409
TI  - Improving computer skill training: behavior modeling, symbolic mental rehearsal,
      and the role of knowledge structures.
AB  - Effective computer skill training is vital to organizational productivity. Two
      experiments (N = 288) demonstrated that the behavior modeling approach to
      computer skill training could be substantially improved by incorporating symbolic
      mental rehearsal (SMR). SMR is a specific form of mental rehearsal that
      establishes a cognitive link between visual images and symbolic memory codes. As
      theorized, the significant effects of SMR on declarative knowledge and task
      performance were shown to be fully mediated by changes in trainees' knowledge
      structures. The mediational role of knowledge structures is expected to
      generalize to other training interventions and cognitive skill domains. Our
      findings have the immediate implications that practitioners should use SMR for
      improving the effectiveness of computer skill training.

PMID- 15161410
TI  - Timing of eyewitness expert testimony, jurors' need for cognition, and case
      strength as determinants of trial verdicts.
AB  - In 2 experiments, college students read a murder-trial transcript that included
      or did not include court-appointed expert testimony about eyewitness memory. The
      testimony either preceded or followed the evidence, and the judge's final
      instructions reminded or did not remind jurors about the expert's testimony.
      Expert testimony decreased perceptions of guilt and eyewitness believability when
      it followed the evidence and preceded the judge's reminder. This effect occurred
      whether the prosecution case was moderately weak or moderately strong. Jurors'
      need for cognition (NC) was curvilinearly related to convictions in a strong
      case. Low and high NC jurors convicted less than did moderate NC jurors. Greater
      scrutiny by high NC jurors may make them more likely to consider evidence for the
      weaker side.

PMID- 15161411
TI  - Intelligence and leadership: a quantitative review and test of theoretical
      propositions.
AB  - Meta-analysis was used to aggregate results from studies examining the
      relationship between intelligence and leadership. One hundred fifty-one
      independent samples in 96 sources met the criteria for inclusion in the meta
      analysis. Results indicated that the corrected correlation between intelligence
      and leadership is.21 (uncorrected for range restriction) and.27 (corrected for
      range restriction). Perceptual measures of intelligence showed stronger
      correlations with leadership than did paper-and-pencil measures of intelligence.
      Intelligence correlated equally well with objective and perceptual measures of
      leadership. Additionally, the leader's stress level and the leader's
      directiveness moderated the intelligence-leadership relationship. Overall,
      results suggest that the relationship between intelligence and leadership is
      considerably lower than previously thought. The results also provide meta
      analytic support for both implicit leadership theory and cognitive resource
      theory.

PMID- 15161412
TI  - A counterintuitive hypothesis about employment interview validity and some
      supporting evidence.
AB  - This study found mixed support for the hypothesis that the difference in
      criterion-related validity between unstructured and structured employment
      interviews is due solely to the greater reliability of structured interviews.
      Using data from prior meta-analyses, this hypothesis was tested in 4 data sets by
      using standard psychometric procedures to remove the effects of measurement error
      in interview scores from correlations with rated job performance and training
      performance. In the 1st data set. support was found for this hypothesis. However,
      in a 2nd data set structured interviews had higher true score correlations with
      performance ratings, and in 2 other data sets unstructured interviews had higher
      true score correlations. We also found that averaging across 3 to 4 independent
      unstructured interviews provides the same level of validity for predicting job
      performance as a structured interview administered by a single interviewer.
      Practical and theoretical implications are discussed.

PMID- 15161413
TI  - Charting the language of leadership: a methodological investigation of President
      Bush and the crisis of 9/11.
AB  - In many ways, leadership is a phenomenon that is ideally suited for new and
      inventive research methods. For researchers who seek to reliably study and
      systematically compare linguistically based elements of the leadership
      relationship, computerized content analysis has the potential to supplement,
      extend, and qualify existing leadership theory and practice. Through an
      examination of President Bush's rhetoric and the media coverage before and after
      the crisis of 9/11. the authors explore how elements of the President's speeches
      changed in response to the post-crisis environment. Using this example, the
      authors illustrate the process of computerized content analysis and many of its
      strengths and limitations, with the hope of facilitating future leadership
      research that uses this approach to explore important contextual and symbolic
      elements of the leadership relationship.

PMID- 15161414
TI  - Are the characteristics of narrative comments related to improvement in
      multirater feedback ratings over time?
AB  - Researchers have paid almost no attention to the narrative comments that
      typically accompany multirater feedback reports despite the fact that both
      anecdotal and empirical evidence suggest that feedback recipients devote
      considerable attention to such comments. The authors examined improvement in
      upward feedback ratings over a 1-year period for 176 managers as a function of
      (a) the number of narrative comments each manager received, (b) whether those
      comments were favorable (vs. unfavorable), and (c) whether the comments were
      behavior/task focused (vs. trait focused). The authors found that managers who
      received a small number of unfavorable, behavior/task-focused comments improved
      more than did other managers, whereas managers who received a large number of
      unfavorable, behavior/task-focused comments declined more than did other
      managers.

PMID- 15161415
TI  - Scholarship: it's not an option, it's a necessity.

PMID- 15161416
TI  - Individual and societal influences on participation in physical activity
      following spinal cord injury: a qualitative study.
AB  - BACKGROUND AND PURPOSE: Despite evidence that physical activity, a tool of
      rehabilitation, affects health and improves functional ability in people
      following spinal cord injury (SCI), such people are often physically inactive. We
      used a qualitative method to explore the experiences of individuals with SCI
      during participation in physical activity. SUBJECTS: The participants were 8
      adults (5 male, 3 female), ranging from active to inactive, who were 2 to 27
      years post-rehabilitation following SCI (paraplegic). METHODS: We used
      semistructured ethnographic interviews to explore barriers and enablers to
      participation in physical activity following SCI. Emerging themes were derived
      from the participants' experiences. RESULTS: Two themes were identified: (1)
      individual influences, defined as a period of loss of "able identity" and
      subsequent redefinition of self in which participation in physical activity may
      be a vehicle or an outcome, and (2) societal influences, which included
      environmental and attitudinal barriers. DISCUSSION AND CONCLUSION: The
      participants' experiences offer insight for therapists regarding physical
      activity following SCI.

PMID- 15161417
TI  - The role of health promotion in physical therapy in California, New York, and
      Tennessee.
AB  - BACKGROUND AND PURPOSE: As health care providers, physical therapists are in an
      ideal position to address health promotion issues with their patients; yet,
      little is known about actual health promotion practice patterns or the confidence
      of physical therapists in engaging in such activities. The purposes of this study
      were: (1) to investigate perceptions of practice patterns in 4 focus areas of
      Healthy People 2010 (disability and secondary conditions by assessing
      psychological well-being, nutrition and overweight, physical activity and
      fitness, and tobacco use) and (2) to identify related self-efficacy and outcome
      expectations in California, New York, and Tennessee. SUBJECTS: A instrument was
      pilot tested and distributed in 2 waves to 3,500 randomly selected, licensed
      physical therapists from 3 states: California, New York, and Tennessee. METHODS:
      Interviews were randomly conducted via telephone with 23 physical therapists in
      all 3 states until similar responses were identified in order to create the
      qualitative instrument, which was then pilot tested with 20 physical therapists
      in California. The total number of qualitative instruments used in the data
      analyses was 417 (145 from California, 127 from New York, and 145 from Tennessee)
      or 11.9%. RESULTS: The health promotion behavior most commonly thought to be
      practiced by physical therapists was assisting patients to increase physical
      activity (54%), followed by psychological well-being (41%), nutrition and
      overweight issues (19%), and smoking cessation (17%). Self-efficacy predicted all
      4 behaviors beyond the control variables. Minimal state-to-state differences were
      noted. DISCUSSION AND CONCLUSION: Physical therapists believe they are addressing
      health promotion topics with patients, although in varying degrees and in lower
      than desirable percentages based on Healthy People 2010 goals. This study
      demonstrated that a physical therapist's confidence in being able to perform a
      behavior (self-efficacy) was the best predictor of perceptions of practice
      patterns and is an area to target in future interventions.

PMID- 15161418
TI  - Physiologic evidence for the efficacy of positive expiratory pressure as an
      airway clearance technique in patients with cystic fibrosis.
AB  - BACKGROUND AND PURPOSE: Individuals with cystic fibrosis (CF) have large amounts
      of infected mucus in their lungs, which causes irreversible lung tissue damage.
      Although patient-administered positive expiratory pressure (PEP) breathing has
      been promoted as an effective therapeutic modality for removing mucus and
      improving ventilation distribution in these patients, the effects of PEP on
      ventilation distribution and gas mixing have not been documented. Therefore, this
      preliminary investigation described responses in distribution of ventilation and
      gas mixing to PEP breathing for patients with moderate to severe CF lung disease.
      SUBJECTS AND METHODS: The effects of PEP breathing on ventilation distribution,
      gas mixing, lung volumes, expiratory airflow, percentage of arterial blood
      oxyhemoglobin saturation (SpO(2)), and sputum volume were studied in 5 patients
      with CF (mean age=18 years, SD=4, range=13-22) after no-PEP, low-PEP (10-20 cm
      H(2)O), and high-PEP (>20 cm H(2)O) breathing conditions. Single-breath inert gas
      studies and lung function tests were performed before, immediately after, and 45
      minutes after intervention. Single-breath tests assess ventilation distribution
      homogeneity and gas mixing by observing the extent to which an inspired test gas
      mixes with gas already residing in the lung. RESULTS: Improvements in gas mixing
      were observed in all PEP conditions. By 45 minutes after intervention, the no-PEP
      group improved by 5%, the low-PEP group improved by 15%, and the high-PEP group
      improved by 23%. Slow vital capacity increased by 1% for no PEP, by 9% for low
      PEP, and by 13% for high PEP 45 minutes after intervention. Residual volume
      decreased by 13% after no PEP, by 20% after low PEP, and by 30% after high PEP.
      Immediate improvements in forced expiratory flow during the middle half of the
      forced vital capacity maneuver (FEF(25%-75%)) were sustained following high PEP
      but not following low PEP. DISCUSSION AND CONCLUSION: This study demonstrated the
      physiologic basis for the efficacy of PEP therapy. The results confirm that low
      PEP and high PEP improve gas mixing in individuals with CF, and these
      improvements were associated with increased lung function, sputum expectoration,
      and SpO(2). The authors propose that improvements in gas mixing may lead to
      increases in oxygenation and thus functional exercise capacity.

PMID- 15161419
TI  - Physical therapist management of a patient with acute low back pain and elevated
      fear-avoidance beliefs.
AB  - BACKGROUND AND PURPOSE: Elevated fear-avoidance beliefs are believed to be a
      precursor of chronic disability, yet effective intervention options have not been
      described in the literature. The purpose of this case report is to describe
      physical therapist management of a patient with acute low back pain and elevated
      fear-avoidance beliefs. CASE DESCRIPTION: The patient was a 42-year-old sales
      manager with acute low back pain. The patient had no previous history of activity
      limiting low back pain and initially had limitations in straight leg raising,
      limitations in lumbar movement, and elevated fear-avoidance beliefs.
      INTERVENTION: Treatment-based classification and graded exercise were used.
      OUTCOME: Disability, fear-avoidance beliefs, and pain decreased 4 weeks after
      starting physical therapy. Six months later, disability and fear-avoidance
      beliefs had increased, but were still improved when compared with the initial
      measurements. DISCUSSION: Disability and fear-avoidance beliefs improved
      following a fear-avoidance-based physical therapy intervention. Research is
      warranted to investigate the effectiveness of this approach.

PMID- 15161420
TI  - Determination and significance of femoral neck anteversion.

PMID- 15161421
TI  - The measurement of pain in infants, children, and adolescents: from policy to
      practice.

PMID- 15161422
TI  - Pusher syndrome.

PMID- 15161424
TI  - Pusher syndrome.

PMID- 15161423
TI  - Pusher syndrome.

PMID- 15161425
TI  - Targeting B lymphocyte stimulator in systemic lupus erythematosus and other
      autoimmune rheumatic disorders.
AB  - B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression
      of BLyS in mice can lead to systemic lupus erythematosus (SLE)-like disease and
      to Sjogren's syndrome (SS)-like disease. Treatment of mice with established SLE
      with BLyS antagonists ameliorates disease progression and enhances survival.
      Moreover, similar treatment of mice with inflammatory arthritis ameliorates the
      ongoing inflammation and subsequent joint destruction. In humans, BLyS
      overexpression is common in patients with SLE, rheumatoid arthritis or SS.
      Results from a Phase I clinical trial with a BLyS antagonist in human SLE have
      shown the antagonist to be biologically active and safe. These features
      collectively point to BLyS as an attractive therapeutic target in human disease.

PMID- 15161426
TI  - The endothelin system and its role in acute myocardial infarction.
AB  - Endothelin (ET)-1 is a potent coronary vasoconstrictor. On the heart, ET-1 is a
      potent positive inotrope and may be pro-arrhythmic. Plasma ET-1 levels are raised
      after acute myocardial infarction (AMI) and recanalisation in humans. This
      probably contributes to the coronary vasoconstriction that underlies the
      myocardial ischaemia and ventricular dysfunction at this time. During occlusion
      of the rat coronary artery, ventricular arrhythmias are reduced by ET(A) receptor
      blockade. Short-term ET(A) receptor blockade also reduces infarct size in animal
      models of AMI (coronary occlusion followed by reperfusion). Blockade of the
      endothelin-converting enzyme with SM-19712 reduced the infarct size in the rabbit
      model of AMI. ET(A) receptor blockade is associated with coronary artery dilation
      in humans. As there are indications that ET(A) receptor antagonists are
      protective in animal models of AMI, short-term ET(A) receptor blockade should be
      considered for trial in human AMI.

PMID- 15161427
TI  - TNF and congestive heart failure: therapeutic possibilities.
AB  - TNF-alpha is a cytokine that may play a role in the pathogenesis of heart
      failure. In patients with heart failure, increased levels of TNF-alpha were
      observed that were high enough to reduce cardiac contractility in vitro. The
      mortality of heart failure patients increases with higher levels of TNF-alpha.
      For these reasons, inhibition of TNF-alpha appears to be a valid target for the
      improvement of heart failure therapy beyond the current practice of inhibiting
      neurohormonal activation with beta-blockade, angiotensin-converting enzyme (ACE)
      inhibition and aldosterone antagonism. However, whilst this strategy (using
      soluble TNF receptor or TNF antibodies) was successful in smaller short-term
      studies, larger longer-term studies have not revealed any beneficial effect of
      this therapy (RENAISSANCE, RECOVER, RENEWAL, ATTACH). In contrast, the mortality
      tended to be higher in the treated groups giving rise to questions about the
      overall strategy. The reasons for this failure of the clinical studies to show a
      longer-term benefit from TNF-alpha inhibitors are unclear, but they may include
      an error of the general concept, individual adverse effects of the agents used
      for the studies, incorrect dosage and the fact that the current therapy of heart
      failure with beta-blockade, ACE inhibitors and aldosterone antagonists cannot be
      further improved by additional blockade of neurohormones or cytokines.

PMID- 15161428
TI  - Receptor protein tyrosine phosphatase zeta as a therapeutic target for
      glioblastoma therapy.
AB  - Astrocytomas are the most frequent brain tumour type in adults. The most common
      astrocytoma is the glioblastoma (GBM), which is also the most malignant and
      refractory to treatment--ultimately leading to the patient's death within a year
      of diagnosis. Neither the classical nor more experimental therapeutic approaches
      have significantly improved the clinical outcome of this disease. Expression
      profile analysis of primary tumours has provided recent insight into the
      identification of new GBM therapeutic targets. These proteins serve as excellent
      candidates to either inhibit the target molecule's functions (e.g., angiogenesis,
      migration or proliferation) or, coupled with a toxin or radionucleotide, to bind
      and exterminate the tumour cells. The receptor protein tyrosine phosphatase zeta
      (RPTPzeta) and one of its main ligands, pleiotropin (Ptn), are overexpressed in
      GBMs, thus making them potentially very good targets for the development of new
      immunotherapeutics. This review will summarise recent advances in GBM therapies
      focusing on RPTPzeta as a target for immunotherapeutics.

PMID- 15161429
TI  - Targeting mutated tyrosine kinases in the therapy of myeloid leukaemias.
AB  - Myeloid leukaemias are frequently associated with translocations and mutations of
      tyrosine kinase genes. The products of these oncogenes, including BCR-ABL, TEL
      PDGFR, Flt3 and c-Kit, have elevated tyrosine kinase activity and transform
      haematopoietic cells, mainly by augmentation of proliferation and enhanced
      viability. Activated ABL kinases are associated with chronic myeloid leukaemia.
      Mutations in platelet-derived growth factor receptor beta are associated with
      chronic myelomonocytic leukaemia. Flt3 or c-Kit cooperate with other types of
      oncogenes to create fully transformed acute leukaemias. Elevated activity of
      these tyrosine kinases is crucial for transformation, thus making the kinase
      domain an ideal target for therapeutic intervention. Tyrosine kinase inhibitors
      for various kinases are currently being evaluated in clinical trials and are
      potentially useful therapeutic agents in myeloid leukaemias. Here, the authors
      review the signalling activities, mechanism of transformation and therapeutic
      targeting of several tyrosine kinase oncogenes important in myeloid leukaemias.

PMID- 15161430
TI  - Targeting endogenous inhibitors of apoptosis for treatment of cancer, stroke and
      multiple sclerosis.
AB  - The inhibitor of apoptosis (IAP) genes have emerged as probably the most
      important intrinsic regulators of apoptosis. The members of the IAP family are
      highly conserved in evolutionarily distant species and perform the critical role
      of binding to and inhibiting distinct caspases. This inhibition is mediated by
      discrete baculoviral IAP repeat domains that, in a domain-specific manner,
      inhibit either the initiator or executioner caspases. As such the function of
      IAPs lies at the very centre of virtually all apoptotic pathways. Since many, if
      not most, human pathologies involve aberrant apoptosis, the modulation of IAP
      levels or their activity offers huge therapeutic potential for treatment of
      various disorders. Indeed, available data suggest that the therapeutic
      downregulation of IAPs by antisense targeting or their adenovirally-mediated
      overexpression, can in fact be used to successfully modulate cell death.

PMID- 15161432
TI  - Chemoradiation in locally advanced head and neck cancer: new evidence, new
      challenges.

PMID- 15161431
TI  - Ocular angiogenesis: translating preclinical indications to successful clinical
      development.
AB  - Angiogenesis-related ocular diseases such as age-related macular degeneration
      (AMD) or diabetic retinopathy have a high socioeconomic impact in western
      countries and are the leading causes of blindness. Conventional treatment
      modalities for AMD are of limited success. Inhibition of new vessel formation and
      targeting of pathological vessels seem to be the best choice in AMD. A variety of
      animal models mimic the relevant aspects of choroidal neovascularisation (CNV)
      and allow for therapy screening. Preclinical and clinical studies show that a
      variety of different strategies are very promising. Stategies include inhibition
      or blocking of vascular endothelial growth factor, a key player in angiogenesis),
      blocking specific receptors, application of naturally occurring angiogenesis
      inhibitors and gene therapy. However, the multistep pathways involved in ocular
      angiogenesis suggest that a cocktail approach is required for effective long-term
      treatment and prevention of CNV.

PMID- 15161435
TI  - Pemetrexed (Alimta): improving outcomes in malignant pleural mesothelioma.
AB  - During the past four decades, chemotherapy has failed to demonstrate a consistent
      clinical benefit for patients with unresectable or recurrent malignant pleural
      mesothelioma (MPM). Consequently, there has been no standard chemotherapy nor US
      Food and Drug Administration (FDA)-approved drug for patients with this disease.
      The introduction of pemetrexed (Alimta, Eli Lilly), a multitargeted antifolate
      agent, has improved the outlook for patients with mesothelioma by demonstrating a
      positive impact on quality of life and by prolonging survival. Pemetrexed is the
      first FDA-approved drug for the treatment of MPM. The combination of cisplatin
      plus pemetrexed is now the standard of care for the treatment of the disease.
      Furthermore, supplementation with vitamin B12 and folate has vastly improved the
      toxicity profile of pemetrexed. This article summarizes historical chemotherapy
      trials in MPM; discusses key features of clinical trial design for MPM;
      summarizes the results of a landmark Phase III trial of pemetrexed and cisplatin
      in MPM; discusses the relative contributions of pemetrexed and cisplatin to the
      regimen; explains the importance of vitamin supplementation of pemetrexed; and
      provides direction for future clinical trials in this disease.

PMID- 15161434
TI  - Gemcitabine (Gemzar) in non-small cell lung cancer.
AB  - Of the new chemotherapeutic substances of the last decade, gemcitabine (Gemzar,
      Eli Lilly) is probably the most valuable for the treatment of early and advanced
      stage non-small cell lung cancer (NSCLC). When used as a single agent in both
      chemotherapeutically pretreated and chemotherapy-naive patients, gemcitabine
      shows an objective tumor regression rate of approximately 20%. Gemcitabine's
      unique mechanism of action and its lack of overlapping toxicity with other
      cytotoxic agents also define it as an ideal candidate for combination therapy.
      Early clinical development has included single-agent first- and second-line
      treatment, doublet combination regimens and incorporation into multimodality
      treatment strategies for operable and inoperable locally advanced nonmetastatic
      NSCLC. Gemcitabine/platinum-based combination chemotherapy has become the most
      attractive treatment standard for NSCLC patients in good clinical condition. The
      role of gemcitabine in the concurrent or sequential application of chemo- and
      radiotherapy for inoperable locally advanced NSCLC has also been addressed in
      several Phase I and II studies. Based on data available, gemcitabine can be
      safely administered in combination with radiotherapy. This review summarizes
      results from representative Phase I, II and III studies in order to underline
      gemcitabine's clinical importance for patients suffering from early and advanced
      NSCLC.

PMID- 15161436
TI  - Adult T-cell leukemia: future prophylaxis and immunotherapy.
AB  - A small population of human T-cell leukemia virus Type I (HTLV-I) carriers
      develop adult T-cell leukemia after a long incubation period. The results of a
      series of experiments using animal models suggest that insufficiency of HTLV-I
      specific T-cell response induced by vertical HTLV-I infection allows enlargement
      of the HTLV-I-infected cell reservoir in vivo, a crucial risk factor of adult T
      cell leukemia. In this review it is proposed that prophylactic Tax-targeted
      vaccines for the high-risk group of adult T-cell leukemia, which is characterized
      by low HTLV-I-specific T-cell response and high proviral load, can reduce the
      risk. Immunological studies on adult T-cell leukemia patients after hematopoietic
      stem cell transplantation also suggest that Tax-targeted immunotherapy may be
      effective against full-blown disease, although its indication may be limited.

PMID- 15161437
TI  - Colorectal cancer as a complex disease: defining at-risk subjects in the general
      population - a preventive strategy.
AB  - Over the last few decades it has become clear that highly penetrant disease genes
      are responsible for a minor proportion of colorectal cancer cases. Families with
      hereditary syndromes are today recognized and included in surveillance programs
      known to reduce morbidity and mortality in colorectal cancer. Colorectal cancer
      is preventable and screening strategies in whole populations are currently under
      debate. Colorectal cancer can be considered a complex disease, with a combination
      of predisposing genetic variants and environmental factors that contribute to the
      illness as a whole. The progress made in the genome project provides an
      opportunity to determine such genetic variants and environmental factors. This
      knowledge can be used to define a subpopulation at increased risk for colorectal
      cancer. It will be more feasible to design preventive strategies for this
      subgroup than for a whole population.

PMID- 15161438
TI  - Molecular therapeutic approaches to acute myeloid leukemia: targeting aberrant
      chromatin dynamics and signal transduction.
AB  - Acute myeloid leukemia research and clinical management have greatly benefited
      from the achievements in molecular biology regarding the identification of the
      underlying pathogenetic mechanisms of transformation and resistance to therapy.
      In particular, two categories of alterations, the aberrant activity of
      transcription/chromatin-remodeling factors and the deregulated activation of
      signal transduction pathways, have been demonstrated to play a pivotal role in
      leukemic cell differentiation, proliferation and resistance to apoptosis. These
      molecular lesions have proven to be suitable therapeutic targets in acute
      promyelocytic leukemia and chronic myeloid leukemia and are now also seen as
      therapeutic targets for a wider group of leukemic disorders. The development of
      novel drugs such as histone deacetylase inhibitors, demethylating agents and
      inhibitors of receptor tyrosine kinases may potentially benefit acute myeloid
      leukemia patients.

PMID- 15161439
TI  - Current treatment strategies for patients with Hodgkin's lymphoma and HIV
      infection.
AB  - Hodgkin's lymphoma is the most common non-AIDS-defining tumor diagnosed in HIV
      infected patients. Although the introduction of highly active antiretroviral
      therapy (HAART) led to a decreased incidence of several malignancies among HIV
      infected patients, the incidence of HIV-associated Hodgkin's lymphoma (HIV-HL)
      has been persistent in recent years. Its unusually aggressive tumor behavior
      includes a higher frequency of unfavorable histologic subtypes, high stage and
      extranodal involvement by the time of presentation and poor therapeutic outcome,
      in comparison with Hodgkin's lymphoma outside the HIV setting. Treatment of HIV
      HL is challenging considering the underlying immunodeficiency caused by HIV
      itself and may increase the risk of opportunistic infections by inducing further
      immunosuppression. To address this delicate vulnerability of the HIV-infected
      host, tailored regimens, which are less aggressive than standard regimens for HIV
      negative hosts, have been applied to achieve tumor control. The introduction of
      HAART has opened a new perspective in the treatment of HIV-associated
      malignancies. The improved control of HIV infection and the subsequently improved
      survival rates of HIV-infected patients has changed the goal from tumor control
      to cure and new treatment approaches with more potent regimens need to be
      evaluated to improve survival and quality of life in HIV-HL.

PMID- 15161440
TI  - Cancer of the nasal cavity and paranasal sinuses.
AB  - Sinonasal malignancies continue to have poor survival rates. Disease-related
      mortality is usually the result of disease recurrence and progression at the
      primary site despite aggressive therapy. Complete surgical excision with
      postoperative radiation therapy remains the standard of care for resectable
      lesions. Improved reconstructive techniques have increased our ability to
      aggressively clear locally advanced disease in this anatomically challenging
      region, while reducing associated functional and cosmetic morbidity. Intensive
      multimodality treatment regimens coupled with newer medical technology may
      ultimately improve the long-prevailing poor prognosis of these tumors.

PMID- 15161441
TI  - Intensity-modulated radiation therapy for head and neck cancer.
AB  - In head and neck cancer, intensity-modulated radiation therapy (IMRT) makes the
      use of electron beams for irradiation of the posterior neck obsolete, inherently
      performs missing tissue compensation, and allows concave and intentionally
      nonhomogeneous dose distributions. By clinical use of these physical
      characteristics, salivary or lacrimal glands, optic pathway and auditory
      structures can be selectively underdosed and good evidence of decreased radiation
      toxicity is available. Evidence for increased local control is still lacking.
      Recurrences are mainly located in the high-dose-prescription regions, suggesting
      the need for even higher doses in these areas. Image-aided design of IMRT dose
      distribution is an area of intense research. New positron emission tomography and
      magnetic resonance imaging developments might allow definition of volumes inside
      the tumor where treatment failure is most likely to occur. If these volumes are
      small, focused dose escalation of large magnitude can be attempted and the
      hypothesis of improved local control by IMRT can be tested.

PMID- 15161442
TI  - Novel therapies for recurrent ovarian cancer management.
AB  - The search for novel therapies has resulted in a number of biologic agents that
      target cellular processes and molecules involved in ovarian carcinogenesis. These
      drugs include cytokines, monoclonal antibodies, vaccines, protease inhibitors and
      gene replacement systems. Many of these have been evaluated in Phase I/II trials
      and are currently being investigated in Phase III trials. This paper will review
      the progress of and ongoing clinical studies evaluating the potential utility of
      these new agents in patients affected with ovarian cancer. Further development
      and investigation of these agents may eventually lead to a combination of
      treatments that ultimately results in improved survival for patients with ovarian
      cancer.

PMID- 15161443
TI  - Recently elucidated energy catabolism pathways provide opportunities for novel
      treatments in hepatocellular carcinoma.
AB  - It has long been known that tumors depend on energy production pathways that are
      different from those of normal cells. These unique pathways require the
      expression and function of tumor-specific enzymes. Some of these glycolytic
      enzymes, as well as other modulators of tumor behavior, have recently been
      elucidated. In theory, inhibiting such enzymes or appropriately affecting such
      modulators should deprive tumors of energy, while leaving nontransformed cells
      unaffected. These factors include certain hexokinases that catalyze glycolysis in
      tumors and can be inhibited by 3-bromopyruvate. 2-deoxyglucose is another
      modulator that depletes hexokinase stores and cannot undergo further catabolism,
      thus depriving tumors of their energy source. Other enzymes or modulators are
      under scrutiny and have shown promise. Preliminary experiments on animals with
      hepatocellular carcinoma have indeed shown very encouraging results. It appears
      that modulating the energy production pathways of tumors is poised to become a
      substantial research area for cancer treatment. This review will focus on the
      energy production pathways of transformed cells, highlight the differences
      between transformed and normal cells in this regard and summarize recent
      experiments that take advantage of these disparities in cancer treatment.

PMID- 15161444
TI  - Targeted alpha-therapy for control of micrometastatic prostate cancer.
AB  - Carcinoma of the prostate is the second most common cancer in men. In spite of
      the most aggressive therapies, the control of metastatic prostate cancer remains
      an elusive objective and many patients die of secondary disease. Targeted alpha
      therapy is an emerging therapeutic modality whereby a labeled protein selectively
      targets cancer cells and delivers a lethal payload, which can kill cancer cells
      in transit or preangiogenic cell clusters. Recent studies show that targeted
      alpha-therapy is highly cytotoxic to prostate cancer cells in vitro and can
      inhibit tumor growth in animal models. This review will consider alpha-emitting
      radionuclides and current in vitro and in vivo studies with alpha
      radioconjugates, and will focus on cell-surface target antigens and targeting
      vectors for the treatment of prostate cancer.

PMID- 15161445
TI  - Management and geriatric assessment of cancer in the elderly.
AB  - Due to the demographic evolution, the management of elderly patients with cancer
      currently represents a major challenge for the medical community. Aging may be
      associated with an increased rate of health problems possibly resulting in a loss
      of independence. These problems can interfere with cancer treatment strategies.
      Therefore, treatment decision making requires a multidisciplinary and
      multidimensional assessment of both the characteristics of the malignant disease
      and the host's general health status. Several oncological groups have developed
      specific programs for elderly cancer patients. Based on a multidimensional
      geriatric assessment tool, they aim to establish the best pattern of care for the
      population of elderly patients with cancer. Clinical research in geriatric
      oncology is also a very exciting field, particularly regarding the conception of
      clinical trials specifically designed for elderly patients. The particular
      aspects of the management of elderly patients with cancer and some critical
      challenges of clinical research will be presented and discussed in this review.

PMID- 15161446
TI  - Comprehensive approach to advanced primary and recurrent ovarian cancer: a
      personal experience.
AB  - Despite improvements in chemotherapy agents and schedules and new drug
      combinations, epithelial ovarian cancer remains a leading cause of gynecologic
      cancer death in Western countries. It is usually diagnosed at late stages of the
      disease, which makes complete surgical resection technically more difficult. The
      targeted comprehensive approach described in this review includes cytoreductive
      surgery and perioperative intraperitoneal chemotherapy. The goal of this
      aggressive therapy is to remove all the macroscopic disease with the use of
      peritonectomy procedures and visceral resections, and also to eradicate
      microscopic disease using heated intraoperative intraperitoneal chemotherapy and
      early postoperative intraperitoneal chemotherapy. Patients that received a
      complete cytoreduction followed by perioperative intraperitoneal chemotherapy had
      an improved survival, with reasonable morbidity and mortality, as compared with
      those who received incomplete cytoreduction.

PMID- 15161447
TI  - Potentially inappropriate prescribing in Ontario community-dwelling older adults
      and nursing home residents.
AB  - OBJECTIVES: To compare patterns of potentially inappropriate drug therapy
      prescribing in community-dwelling older adults and nursing home residents in
      Ontario, Canada. DESIGN: A retrospective cohort study using administrative
      databases. SETTING: Ontario community and nursing home facilities. PARTICIPANTS:
      All 1,275,619 older adults aged 66 and older in Ontario (1,216,900 community
      dwelling and 58,719 nursing home residents) who were dispensed at least one
      prescription from the comprehensive provincial drug plan in 2001. In Ontario, the
      provision of clinical pharmacy services is mandated in the nursing home setting.
      No comparable program exists for older adults in the community setting.
      MEASUREMENTS: Potentially inappropriate drug prescribing was compared between
      community-dwelling and nursing home residents in two categories: those to always
      avoid and therapies considered rarely appropriate to prescribe. RESULTS: Of the
      1,275,619 adults in the cohort, nursing home residents were older (mean age+/
      standard deviation=84.2+/-7.6 vs 75.0+/-6.5, P<.001), included more women (73.3%
      vs 57.7%, P<.001), had higher comorbidity scores (measured by the number of
      distinct drug therapies dispensed in the prior year (10.7+/-6.8 vs 7.2+/-5.7,
      P<.001) and Charlson comorbidity scores (1.4+/-1.6 vs 0.9+/-1.5, P<.001)) than
      community-dwelling individuals. Community-dwelling older adults were
      significantly more likely to be dispensed at least one drug therapy in the always
      avoid or rarely appropriate category than nursing home residents (3.3% vs 2.3%,
      P<.001). Using a logistic regression model that controlled for age, sex, and
      comorbidity (number of distinct drug therapies dispensed in the prior year),
      nursing home residents were close to half as likely to be dispensed one of these
      potentially inappropriate drug therapies as community-dwelling older adults (odds
      ratio=0.52, 95% confidence interval=0.49-0.55, P<.001). CONCLUSION: Potentially
      inappropriate drug therapy in the always avoid and rarely indicated categories is
      dispensed less often to nursing home residents than to older community-dwelling
      adults. Clinical pharmacist services, which are mandated in the nursing home
      setting, may be responsible for these differences in Ontario, Canada.

PMID- 15161448
TI  - Persistent nonmalignant pain and analgesic prescribing patterns in elderly
      nursing home residents.
AB  - OBJECTIVES: To determine the prevalence of analgesics used, their prescribing
      patterns, and associations with particular diagnoses and medications in patients
      with persistent pain. DESIGN: Cross-sectional study. SETTING: Nursing homes from
      10 U.S. states. PARTICIPANTS: A total of 21,380 nursing home residents aged 65
      and older with persistent pain. MEASUREMENTS: Minimum Data Set (MDS) assessments
      on pain, analgesics, cognitive, functional, and emotional status were summarized.
      Logistic regression models identified diagnoses associated with different
      analgesic classes. RESULTS: Persistent pain as determined using the MDS was
      identified in 49% of residents with an average age of 83; 83% were female.
      Persistent pain was prevalent in patients with a history of fractures (62.9%) or
      surgery (63.6%) in the past 6 months. One-quarter received no analgesics. The
      most common analgesics were acetaminophen (37.2%), propoxyphene (18.2%),
      hydrocodone (6.8%), and tramadol (5.4%). Only 46.9% of all analgesics were given
      as standing doses. Acetaminophen was usually prescribed as needed (65.6%), at
      doses less than 1,300 mg per day. Nonsteroidal antiinflammatory drugs (NSAIDs)
      were prescribed as a standing dose more than 70% of the time, and one-third of
      NSAIDs were prescribed at high doses. CONCLUSION: In nursing home residents,
      persistent pain is highly prevalent, there is suboptimal compliance with
      geriatric prescribing recommendations, and acute pain may be an important
      contributing source of persistent pain. More effective provider education and
      research is needed to determine whether treatment of acute pain could prevent
      persistent pain.

PMID- 15161450
TI  - Incidence of tooth loss and prosthodontic dental care: effect on chewing
      difficulty onset, a component of oral health-related quality of life.
AB  - OBJECTIVES: To quantify incidence of tooth loss, prosthodontic dental
      restoration, and chewing difficulty onset and the effect of tooth loss and
      prosthodontic restoration on chewing difficulty onset. DESIGN: A prospective
      cohort study of oral health and related behaviors with in-person interviews and
      clinical examinations conducted at baseline and 24 months. Telephone interviews
      were conducted every 6 months between these sessions. SETTING: A community-based
      sample of four counties in north Florida. PARTICIPANTS: Eight hundred seventy
      three persons who had at least one tooth and were aged 45 and older at baseline.
      MEASUREMENTS: Persons were queried regarding onset of chewing difficulty, an
      important component of oral health-related quality of life (OHRQoL). The chewing
      index of Leake, with minor revision, was the primary outcome of interest. Tooth
      loss was measured using direct clinical examination. Dental care use was reported
      during each interview. RESULTS: Approximately 22% of participants reported tooth
      loss during follow-up. Fixed prosthodontics (crowns and bridges) was the most
      common form of new prosthodontic treatment. People who reported tooth loss were
      2.7 times more likely to report chewing difficulty onset than people without
      tooth loss (P<.001). Having fewer occluding pairs of teeth at baseline was
      significantly associated with an increased probability of chewing difficulty
      onset. People who received removable prosthodontic treatment were much less
      likely to report chewing difficulty onset than people who did not (P<.01).
      CONCLUSION: Incident tooth loss and removable prosthodontic restoration strongly
      predicted chewing difficulty, an important component of OHRQoL.

PMID- 15161449
TI  - Office evaluation and treatment of elderly patients with acute bronchitis.
AB  - OBJECTIVES: To assess the office evaluation of seniors with uncomplicated acute
      bronchitis and to determine the association between elements of the clinical
      evaluation and antibiotic prescribing decisions. DESIGN: Cross-sectional chart
      review. SETTING: Seventy-seven community-based office practices in the Denver
      metropolitan area. PARTICIPANTS: Elderly fee-for-service Medicare patients.
      MEASUREMENTS: Medicare administrative data to identify patients with acute
      bronchitis; medical record review to confirm the diagnosis and record other
      clinical data. RESULTS: Of 198 elderly patients with acute bronchitis, the mean
      age+/-standard deviation was 76+/-8.6; 53% had at least one comorbid condition.
      Clinically important vital signs were frequently not recorded; temperature was
      missing from 34% of charts and pulse from 50% of charts. When recorded,
      significant vital sign abnormalities were uncommon, with 7% having a temperature
      of 100 degrees F and 8% having a pulse of 100 beats per minute or greater.
      However, antibiotics were prescribed to 83% of patients, with more than half of
      these prescriptions being for extended-spectrum antibiotics. Treatment with
      antibiotics was more common in men than women (92% vs 78%, P=.007) but was not
      associated with clinical factors including vital sign measurement, vital sign
      results, chest radiography, patient age, duration of illness, or the presence of
      comorbidities. CONCLUSION: The vast majority of seniors with acute bronchitis are
      treated with antibiotics, regardless of patient characteristics or the type of
      evaluation received. Reducing inappropriate antibiotic use in seniors with acute
      bronchitis may depend on improving the evaluation of these patients and
      encouraging clinicians to act appropriately on the results.

PMID- 15161451
TI  - Body mass index, body cell mass, and 4-year all-cause mortality risk in older
      nursing home residents.
AB  - OBJECTIVES: To investigate the relationship between body composition (assessed
      using body mass index (BMI) and body cell mass (BCM)) and all-cause mortality in
      a sample of older nursing home residents. DESIGN: Prospective study with a median
      follow-up period of 3.5 years. SETTING: Istituto di Riposo per Anziani, Padua,
      Italy. PARTICIPANTS: A total of 344 participants (79.1% women) aged 65 and older
      at baseline. MEASUREMENTS: Anthropometric, nutritional, and metabolic parameters
      were measured at baseline. BCM was measured using tetrapolar bioelectric
      impedance analysis. Up to 4 years of follow-up data for vital status were
      available. Survival analysis was conducted using Kaplan-Meier curves and
      multivariate Cox proportional hazards models. RESULTS: During the follow-up
      period, there were 179 deaths. After adjustment for age and sex, subjects with
      low BMI and low BCM (lowest sex-specific tertiles) had significantly higher
      mortality than those with higher BMI or BCM levels. In a fully adjusted
      regression model, there was no association between BMI levels and risk of
      mortality, with subjects in the top tertile having the same likelihood of
      mortality as subjects in the lowest tertile (relative risk (RR)=0.94, 95%
      confidence interval (CI)=0.61-1.43). Conversely, there was a strong and
      significant inverse association between BCM levels and mortality (RR for tertile
      III=0.55, 95% CI=0.35-0.87; P<.01). Furthermore, participants who had high BCM
      had comparable survival rates in all BMI tertiles. CONCLUSION: In this sample of
      older nursing home residents, BCM was a strong and independent risk factor for
      mortality. BCM assessment might provide more useful prognostic information for
      clinicians than BMI.

PMID- 15161452
TI  - Tai chi and self-rated quality of sleep and daytime sleepiness in older adults: a
      randomized controlled trial.
AB  - OBJECTIVES: To determine the effectiveness of tai chi on self-rated sleep quality
      and daytime sleepiness in older adults reporting moderate sleep complaints.
      DESIGN: Randomized, controlled trial with allocation to tai chi or exercise
      control. SETTING: General community. PARTICIPANTS: One hundred eighteen women and
      men aged 60 to 92. INTERVENTION: Participants were randomized into tai chi or low
      impact exercise and participated in a 60-minute session, three times per week,
      for 24 consecutive weeks. MEASUREMENTS: Primary outcome measures were the seven
      subscales of the Pittsburgh Sleep Quality Index (PSQI), PSQI global score, and
      Epworth Sleepiness Scale (ESS). Secondary outcome measures were physical
      performance (single leg stand, timed chair rise, 50-foot speed walk) and 12-item
      short form (SF-12) physical and mental summary scores. RESULTS: Tai chi
      participants reported significant improvements in five of the PSQI subscale
      scores (sleep quality, sleep-onset latency, sleep duration, sleep efficiency,
      sleep disturbances) (P<.01), PSQI global score (P=.001), and ESS scores (P=.002)
      in comparison with the low-impact exercise participants. Tai chi participants
      reported sleep-onset latency of about 18 minutes less per night (95% confidence
      interval (CI)=-28.64 to -7.12) and sleep duration of about 48 minutes more per
      night (95% CI=14.71-82.41) than low-impact exercise participants. Tai chi
      participants also showed better scores in secondary outcome measures than low
      impact exercise participants. Both groups reported improvements in SF-12 mental
      summary scores. CONCLUSION: Older adults with moderate sleep complaints can
      improve self-rated sleep quality through a 6-month, low- to moderate-intensity
      tai chi program. Tai chi appears to be effective as a nonpharmacological approach
      to sleep enhancement for sleep-disturbed elderly individuals.

PMID- 15161454
TI  - Thoracic kyphosis and ventilatory dysfunction in unselected older persons: an
      epidemiological study in Dicomano, Italy.
AB  - OBJECTIVES: To assess whether kyphosis is associated with ventilatory dysfunction
      in older community dwellers. DESIGN: Cross-sectional study. SETTING: The
      unselected population of Dicomano, Italy aged>or=65 years. PARTICIPANTS: A total
      of 323 nonheart failure participants underwent clinical evaluation for the
      presence of kyphosis and spirometry. The severity of kyphosis was estimated from
      the difference between standing stature and knee-height-derived stature and from
      the occiput-wall distance. MEASUREMENTS: Forced vital capacity (FVC), forced
      expiratory volume in 1 second (FEV1), and prevalence of obstructive and
      restrictive ventilatory pattern. RESULTS: The 130 kyphotic participants (40.2%)
      had an adjusted 2.5 prevalence odds ratio (POR) for dyspnea (95% confidence
      interval (CI)=1.1-5.8). FVC% and FEV1% were lower in the presence of kyphosis
      (P<.01); their deficit was proportional to kyphosis severity. The ventilatory
      dysfunction was underestimated when reference spirometric parameters were
      calculated based on standing stature, compared with knee-height derived stature.
      Of the kyphotic participants, 56.2%, 26.9%, and 16.9% had spirometric normal,
      obstructive, and restrictive patterns, respectively. Kyphosis was associated with
      a restrictive (adjusted POR=2.3, 95% CI=1.1-4.8; P=.021) and an obstructive
      ventilatory pattern (adjusted POR=3.3, 95% CI=1.7-6.5; P<.001). CONCLUSION: In
      unselected older persons, kyphosis is associated with dyspnea and ventilatory
      dysfunction of a restrictive and an obstructive type. Kyphosis should be included
      in the differential diagnosis of dyspnea and ventilatory dysfunction in the
      elderly.

PMID- 15161453
TI  - Whole-body-vibration training increases knee-extension strength and speed of
      movement in older women.
AB  - OBJECTIVES: To investigate the effects of 24 weeks of whole-body-vibration (WBV)
      training on knee-extension strength and speed of movement and on counter-movement
      jump performance in older women. DESIGN: A randomized, controlled trial. SETTING:
      Exercise Physiology and Biomechanics Laboratory, Leuven, Belgium. PARTICIPANTS:
      Eighty-nine postmenopausal women, off hormone replacement therapy, aged 58 to 74,
      were randomly assigned to a WBV group (n=30), a resistance-training group (RES,
      n=30), or a control group (n=29). INTERVENTION: The WBV group and the RES group
      trained three times a week for 24 weeks. The WBV group performed unloaded static
      and dynamic knee-extensor exercises on a vibration platform, which provokes
      reflexive muscle activity. The RES group trained knee-extensors by performing
      dynamic leg-press and leg-extension exercises increasing from low (20 repetitions
      maximum (RM)) to high (8RM) resistance. The control group did not participate in
      any training. MEASUREMENTS: Pre-, mid- (12 weeks), and post- (24 weeks) isometric
      strength and dynamic strength of knee extensors were measured using a motor
      driven dynamometer. Speed of movement of knee extension was assessed using an
      external resistance equivalent to 1%, 20%, 40%, and 60% of isometric maximum.
      Counter-movement jump performance was determined using a contact mat. RESULTS:
      Isometric and dynamic knee extensor strength increased significantly (P<.001) in
      the WBV group (mean+/-standard error 15.0+/-2.1% and 16.1+/-3.1%, respectively)
      and the RES group (18.4+/-2.8% and 13.9+/-2.7%, respectively) after 24 weeks of
      training, with the training effects not significantly different between the
      groups (P=.558). Speed of movement of knee extension significantly increased at
      low resistance (1% or 20% of isometric maximum) in the WBV group only (7.4+/-1.8%
      and 6.3+/-2.0%, respectively) after 24 weeks of training, with no significant
      differences in training effect between the WBV and the RES groups (P=.391;
      P=.142). Counter-movement jump height enhanced significantly (P<.001) in the WBV
      group (19.4+/-2.8%) and the RES group (12.9+/-2.9%) after 24 weeks of training.
      Most of the gain in knee-extension strength and speed of movement and in counter
      movement jump performance had been realized after 12 weeks of training.
      CONCLUSION: WBV is a suitable training method and is as efficient as conventional
      RES training to improve knee-extension strength and speed of movement and counter
      movement jump performance in older women. As previously shown in young women, it
      is suggested that the strength gain in older women is mainly due to the vibration
      stimulus and not only to the unloaded exercises performed on the WBV platform.

PMID- 15161455
TI  - Lipoprotein levels are associated with incident hypertension in older adults.
AB  - OBJECTIVES: To determine the relationship between baseline measures of serum
      lipoproteins and incident hypertension in older adults. DESIGN: Prospective
      cohort study. SETTING: Pittsburgh, Pennsylvania, site of Systolic Hypertension in
      the Elderly Program (SHEP). PARTICIPANTS: One hundred eighty-seven men and women
      (mean age 71.3), normotensive (systolic blood pressure (SBP) <160 mmHg, diastolic
      blood pressure (DBP) <90 mmHg) at baseline, were followed annually over 8 years
      as an ancillary study to the SHEP. MEASUREMENTS: Hypertension development,
      defined as initiation of antihypertensive therapy or SBP greater than 160 mmHg or
      DBP greater than 90 mmHg. Lipoprotein measures included total cholesterol, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C),
      HDL(2)-C, HDL(3)-C, triglycerides, and apolipoproteins 1, 2, and B. RESULTS: Over
      8 years, 44 participants developed hypertension, for a Kaplan-Meier cumulative
      incidence rate of 31% (95% confidence interval (CI)=23-39%). Cumulative incidence
      rates were highly associated with baseline SBP, ranging from 8% in those with
      baseline SBP less than 120 mmHg to 70% in those with SBP of 140 to 159 mmHg.
      Other univariate associations included higher DBP, pulse pressure (P <.01 for
      both), triglycerides (P=.03), apolipoprotein B (P=.03), and lower HDL-C (P=.04)
      and HDL(3)-C (P=.02). In multivariate Cox regression analysis, higher baseline
      SBP (relative risk (RR)=1.8 per 10 mmHg, 95% CI=1.5-2.3) and lower HDL(3)-C
      (RR=0.8 per 5 mg/dL, 95% CI=0.42-1.0) remained significant independent predictors
      of time to hypertension. CONCLUSION: Older adults with abnormal serum
      lipoproteins are at increased risk of developing hypertension. Clinical trials
      exploring the effects of the modification of lipoprotein levels on hypertension
      incidence rates are needed.

PMID- 15161456
TI  - Peripheral arterial disease in African Americans: clinical characteristics, leg
      symptoms, and lower extremity functioning.
AB  - OBJECTIVES: The describe peripheral arterial disease (PAD) in African Americans,
      and compare findings in African Americans and whites with PAD. DESIGN: Cross
      sectional. SETTING: Three academic medical centers. PARTICIPANTS: Three hundred
      sixty-six whites and 76 African Americans with PAD (as defined by an ankle
      brachial index (ABI) <0.90) aged 55 and older identified from lower extremity
      arterial studies performed between 1996 and the fall of 1999. MEASUREMENTS:
      Comprehensive medical interview, body mass index, and neuropathy score.
      Functional measurements included the 6-minute walk distance, 4-m walking
      velocity, and the summary performance score. RESULTS: Age- and sex-adjusted
      results showed that African Americans had a lower mean ABI than whites (0.60 vs
      0.66, P=.001), were less likely to be college graduates (13.7% vs 44.4%, P<.001),
      and had nearly twice the prevalence of diabetes mellitus (46.8% vs 28.0%,
      P=.001). After adjusting for age, sex, education level, and ABI, African
      Americans had a higher prevalence of no exertional leg pain (28.0% vs 18.2%,
      P=.044) and leg pain with exertion and rest (30.0% vs 17.3%, P=.023). African
      Americans had a shorter 6-minute walk distance (989 vs 1,156 ft, P<.001), a
      slower normal-pace 4-m walking velocity (0.79 vs 0.89 m/s, P<.001), a slower fast
      pace 4-m walking velocity (1.12 vs 1.20 m/s, P=.012), and a lower summary
      performance score (8.8 vs 9.6, P=.018) than whites. These differences in
      functioning were attenuated after adjusting for age, sex, ABI, education, and leg
      symptoms. CONCLUSION: Poorer lower extremity functioning in African Americans was
      largely explained by differences in leg symptoms and, to a somewhat lesser
      degree, lower ABI levels and poorer education in African Americans than in
      whites. Further study is needed to determine whether these findings affect racial
      treatment disparities and poorer outcomes previously reported in African
      Americans than in whites with PAD.

PMID- 15161457
TI  - The effects of staffing on in-bed times of nursing home residents.
AB  - OBJECTIVES: To examine the effect of staffing level on time observed in bed
      during the daytime in nursing home (NH) residents. DESIGN: Descriptive, cross
      sectional study. SETTING: Thirty-four southern California NHs. PARTICIPANTS: A
      total of 882 NH residents: 837 had hourly observation data, 777 had mealtime
      observations, 837 completed interviews, and 817 completed a physical performance
      test. MEASUREMENTS: Cross-sectional data collected from participants at each NH
      site included direct observations (hourly and mealtime), resident interviews,
      medical record review, and physical performance tests. RESULTS: In multivariate
      analyses, staffing level remained the strongest predictor of time observed in bed
      after controlling for resident functional measures (odds ratio=4.89; P=.042).
      Residents observed in bed during the daytime in more than 50% of hourly
      observations were observed also to experience increased daytime sleeping (P<.001)
      and less social engagement (P=.026) and consumed less food and fluids during
      mealtimes than those observed in bed in less than 50% of observations, after
      adjusting for resident function (P<.001). CONCLUSION: In this sample of NHs,
      resident functional measures and NH staffing level predicted observed time in bed
      according to hourly observations, with staffing level the most powerful
      predictor. Neither of these predictors justifies the excessive in-bed times
      observed in this study. Staff care practices relevant to encouraging residents to
      be out of bed and resident preferences for being in bed should be examined and
      improved. Practice recommendations regarding in-bed time should be considered,
      and further research should seek to inform the development of such
      recommendations.

PMID- 15161459
TI  - Effects of aging, menopause, and hormone replacement therapy on forearm skin
      elasticity in women.
AB  - OBJECTIVES: To investigate the decline per year in skin elasticity in
      postmenopausal women and how much hormone replacement therapy (HRT) increased
      elasticity over 12 months. DESIGN: Observational study of convenience sample.
      SETTING: The Cardiovascular Hospital of Central Japan, a cardiovascular medical
      center. PARTICIPANTS: One hundred seventy-six postmenopausal subjects, mean age+/
      standard deviation=61.3+/-9.1. MEASUREMENTS: In Study 1, skin elasticity was
      measured in the right forearm using a suction device. Comparisons also were made
      with 45 premenopausal subjects (aged 34.5+/-9.9). Skin elasticity in the right
      forearm was measured using the same device at baseline and 12 months after
      initiation of HRT. INTERVENTIONS: In Study 2, 12 postmenopausal subjects (mean
      age=57.1+/-7.4, range 49-71) received conjugated equine estrogen (0.625 mg/d) in
      combination with medroxyprogesterone acetate (2.5 mg/d) for 12 months. RESULTS:
      In Study 1, significant negative correlations between skin elasticity and age and
      years since menopause were found (r=-0.60, P<.001 for each), as well as a 0.55%
      decline per year in skin elasticity. In Study 2, 12 months of HRT significantly
      increased skin elasticity in postmenopausal subjects, by 5.2%. CONCLUSION: After
      menopause, skin elasticity declined 0.55% per year; 12 months of HRT increased
      elasticity by 5.2%.

PMID- 15161458
TI  - Determinants of lower-body muscle power in early postmenopausal women.
AB  - OBJECTIVES: To investigate the association between muscle size, density, and
      fiber composition; body composition; maximal isometric knee extension strength
      (KES); and lower-body muscle power in healthy postmenopausal women. DESIGN: Cross
      sectional analysis of baseline data from a 1-year randomized controlled
      experiment. SETTING: University-based research laboratory. PARTICIPANTS: Seventy
      eight healthy postmenopausal women aged 50 to 57. MEASUREMENTS: Maximal lower
      body muscle power was assessed using vertical jump height (VJH). Maximal
      isometric KES was measured on a dynamometer chair. Computed tomography scans were
      used to determine lean-tissue cross-sectional area and density of the thigh and
      lower leg muscles. Relative area occupied by type I, IIa, IIax, and IIx muscle
      fibers was assessed from the vastus lateralis muscle. lean body mass and total
      body fat mass were assessed using bioelectrical impedance. RESULTS: High VJH was
      associated with low body fat mass, high KES, and high density of thigh and lower
      leg muscles. Multivariate linear regression modeling revealed that high thigh
      muscle density (beta=0.242; P=.019), relative area occupied by the fastest muscle
      fiber types (IIax+IIx; beta=0.246; P=.007), KES (beta=0.247; P=.007), and low
      body fat mass (beta=-0.455; P<.001) were independently associated with high VJH,
      accounting for 45% of the variability in VJH. CONCLUSION: This study showed that
      thigh muscle composition, muscle strength, and body fat mass are important
      determinants of lower-body muscle power production during weight-bearing activity
      in healthy postmenopausal women.

PMID- 15161460
TI  - Identification of strategies used to cope with chronic pain in older persons
      receiving primary care from a Veterans Affairs Medical Center.
AB  - OBJECTIVES: To identify the strategies used by older persons to cope with chronic
      noncancer pain, determine the perceived effectiveness of the strategies, and
      ascertain factors associated with their use. DESIGN: Cross-sectional telephone
      survey. SETTING: Primary care practice located at a Veterans Affairs Medical
      Center in New England. PARTICIPANTS: Two hundred forty-five patients (aged 65-90)
      with chronic pain. MEASUREMENTS: Qualitative methods were used to ascertain
      participants' coping strategies, and their effectiveness was determined using a
      five-category response scale (1=not at all effective to 5=extremely effective).
      In multivariate analyses, associations between participants' demographic,
      medical, psychosocial, and pain characteristics and prevalent coping strategies
      were assessed. RESULTS: Participants had a mean age+/-standard deviation of 75+/
      5.1; 84% were male. Overall, 240 (98%) participants had employed at least one
      coping strategy in the previous month; the mean number used per participant was
      2.8+/-1.4. Prevalent coping strategies included analgesic medications (used by
      187/240=78% participants), exercise (35%), cognitive methods (37%), religious
      activities (21%), and activity restriction (20%). The proportion of participants
      who used a given strategy and rated it quite a bit or extremely effective
      exceeded 50% for only five of the 15 identified strategies. Women were more
      likely than men to use cognitive coping methods (odds ratio (OR)=3.2, 95%
      confidence interval (CI)=1.5-6.8) and religious activities (OR=2.6, 95% CI=1.2
      5.7). Participants with chronic pain due to a musculoskeletal cause were more
      likely to use analgesic medications than those with pain due to all other causes
      (OR=3.2, 95% CI=1.6-6.4), whereas those with trauma-related pain were less likely
      to use exercise than those with pain due to all other causes (OR=0.2, 95% CI=0.1
      0.7). CONCLUSION: Older primary care patients use a broad variety of coping
      strategies to cope with chronic pain. Studies are needed to confirm these
      findings in other older populations and to characterize the longitudinal effects
      of the coping strategies. Given the finding that the perceived effectiveness of
      most coping strategies was modest, efforts to increase their effectiveness in
      older persons are indicated.

PMID- 15161461
TI  - Sleep-disordered breathing and nocturia in older adults.
AB  - OBJECTIVES: To investigate the relationship between sleep-disordered breathing
      (SDB) and nocturia episodes in community-dwelling older adults. DESIGN: A cross
      sectional study. SETTING: Community. PARTICIPANTS: Community-dwelling older
      adults (N=72) recruited from independent living facilities and adult learning
      centers in Atlanta, Georgia. MEASUREMENTS: Three-day voiding diary, ambulatory
      sleep recording, focused physical examination, Epworth Sleepiness Scale, and
      Geriatric Depression Scale. RESULTS: Fifty-eight of the 72 subjects completed the
      study. The mean age+/-standard deviation was 77.7+/-6.7; 44 (76%) were female. Of
      the 58 subjects, 26 (45%) had an apnea-hypopnea index (AHI) of less than 10 per
      hour of sleep, 21 (36%) had an AHI between 10 and 24 per hour sleep, and 11 (19%)
      had an AHI of 25 or higher per hour of sleep. The mean nocturia episodes were
      1.7+/-1.1, 1.6+/-0.9, and 2.6+/-1.4 for subjects in these groups, respectively
      (F=3.82; P=.028). Those with an AHI of 25 or higher had more nocturia episodes,
      higher mean arterial blood pressure, and higher body mass index than those with a
      lower AHI. CONCLUSION: These results suggest that older adults with severe SDB
      have a greater number of nocturia episodes. These findings underscore the
      importance of considering SDB as a differential diagnosis in the evaluation of
      older patients with nocturia.

PMID- 15161463
TI  - The "nondipper" elderly: a clinical entity or a bias?
AB  - OBJECTIVES: To determine the prevalence of nondipper (ND) blood pressure profile
      in the elderly and to ascertain whether the ND pattern of ambulatory blood
      pressure in the elderly is an artifact or represents a specific clinical entity.
      DESIGN: Cross-sectional, observational study. SETTING: Cardiovascular diagnostic
      center, division of geriatrics, secondary care, institutional practice.
      PARTICIPANTS: Sixty-five consecutive community-dwelling elderly hypertensive
      patients referred to the cardiovascular center. MEASUREMENTS: The patients
      underwent actigraphy and ambulatory blood pressure monitoring and completed a
      sleep assessment questionnaire. Patients were divided based on the night-time
      decrease in blood pressure (>10%: "dippers" (n=19); <10%: "NDs" (n=46)). RESULTS:
      Nondippers displayed poorer quality of sleep, as demonstrated objectively by
      actigraphic data; they obtained a higher mean score+/-standard deviation on the
      sleep questionnaire (4.6+/-2.9 vs 3.0+/-1.1, P=.030) and were taking more
      benzodiazepines (33.1% vs 10.7%, P=.035), indicating that their usual sleep
      quality was worse than that of dippers. Multivariate analysis showed a strong
      correlation between nondipper profile and quality of sleep and also with
      comorbidity, total number of drugs being taken, and pulse pressure. CONCLUSION:
      Actigraphy demonstrates impaired sleep in the nondipper elderly. Nevertheless,
      the nondipping pattern seems independent of the discomfort of cuff-inflation
      during the night and occurs in association with higher comorbidity and
      polypharmacy; therefore, it cannot be considered a "bias," but is related to
      detrimental clinical conditions that should be studied in depth.

PMID- 15161462
TI  - Antihypertensive medications and differences in muscle mass in older persons: the
      Health, Aging and Body Composition Study.
AB  - OBJECTIVES: To evaluate whether older persons using angiotensin-converting enzyme
      (ACE) inhibitors have a larger lower extremity muscle mass (LEMM) than users of
      other antihypertensive drugs. DESIGN: Cross-sectional analysis of data from the
      Health, Aging and Body Composition (Health ABC) Study. SETTING: University of
      Tennessee, Memphis, and University of Pittsburgh clinics. PARTICIPANTS: A
      community-based sample of 2,431 well functioning participants of the Health ABC,
      aged 70 to 79, who were free of heart failure, were selected according to use of
      antihypertensive medications: ACE inhibitors (n=197), beta-blockers (n=169),
      thiazides (n=216), calcium-channel blockers (n=340), or none (n=1,509).
      MEASUREMENTS: LEMM, assessed using dual-energy x-ray absorptiometry, compared by
      index drug in analysis of variance models unadjusted and adjusted for
      demographics, study site, height, body fat, physical activity, blood pressure,
      coronary artery disease, diabetes mellitus, and chronic pulmonary disease.
      RESULTS: LEMM significantly differed across the study groups, being larger in
      users of ACE inhibitors than in users of other drugs (unadjusted and adjusted
      models). LEMM was comparable in users of ACE inhibitors and no drug users. A
      trend toward larger LEMM was also observed in sex- and ethnicity-stratified
      analyses and in the subgroup of noncoronary hypertensive participants.
      CONCLUSION: In older persons, use of ACE inhibitors is associated cross
      sectionally with larger LEMM. This finding suggests a possible explanation of the
      benefits of ACE inhibitors in wasting syndromes. If confirmed in longitudinal
      studies, this pharmacological action might have important implications for the
      prevention of physical disability in older patients with hypertension.

PMID- 15161464
TI  - Reliability of the 400-m usual-pace walk test as an assessment of mobility
      limitation in older adults.
AB  - OBJECTIVES: To assess the test-retest reliability of the 400-m usual-pace walk
      test (400-MWT), and to determine whether the 4-m walk test predicts inability to
      walk 400 m. DESIGN: Observational. SETTING: Community, 20-m tract course.
      PARTICIPANTS: Sixty study participants (aged>or=65) were enrolled from the
      community and met the following eligibility criteria: self-reported difficulty in
      two or more of four functional domains (mobility and exercise tolerance, upper
      extremity function, basic self-care, higher functional tasks of independent
      living) and a score of 18 or higher on the Mini-Mental State Examination.
      METHODS: The 400-MWT and 4-m walk test were each repeated within 7 days. RESULTS:
      The mean age+/-standard deviation of the study population was 84.3+/-6.3; 88.3%
      were women. Nineteen participants (31.7%) failed both 400-MWTs, and 41
      successfully completed both tests (kappa=1). Mean walking speed for the 4-m test
      was 0.87+/-0.18 m/s for those who completed the 400-MWT and 0.53+/-0.17 m/s for
      those who failed (P<.001). The Spearman correlation coefficient between 4-m and
      400-m walking speeds was 0.93. The estimated area under the receiver operating
      characteristic curve between 4-m walking speed and the ability to perform the 400
      MWT was 0.91. The 4-m gait speed averaged less than 0.6 m/s in 80% of subjects
      who failed the 400-MWT. CONCLUSION: The test-retest reliability for inability to
      complete the 400-MWT is high. Four-m walking speed is highly predictive of
      ability to perform the 400-MWT. These findings may prove useful to future
      clinical trials and observational studies that involve assessment of mobility
      limitations in older adults.

PMID- 15161466
TI  - Development and validation of a geriatric knowledge test for medical students.
AB  - OBJECTIVES: To assesses the reliability and validity of a geriatrics knowledge
      test designed for medical students. DESIGN: Cross-sectional studies. SETTING: An
      academic medical center. PARTICIPANTS: A total of 343 (86% of those sampled)
      medical students participated in the initial study, including 137 (76%) first
      year, 163 (96%) third-year, and 43 (86% of those sampled) fourth-year students in
      the 2000-2001 academic year. To cross-validate the instrument, another 165 (92%)
      third-year and 137 (76%) first-year students participated in the study in the
      2001-2002 academic year. MEASUREMENTS: An 18-item geriatrics knowledge test was
      developed. The items were selected from a pool of 23 items. An established
      instrument assessing the clinical skills of medical students was included in the
      validation procedure. RESULTS: The instrument demonstrated good reliability
      (Cronbach alpha=0.80) and known-groups and concurrent validity. Geriatrics
      knowledge scores increased progressively with the higher level of medical
      training (mean percentage correct=31.3, 65.3, and 66.5 for the first-year, third
      year, and fourth-year classes, respectively, P<.001). A significant (P<.01)
      relationship was found between the third-year students' geriatrics knowledge and
      their clinical skills. Similar results, except the relationship between knowledge
      and clinical skills, were found in the cross-validation study, supporting the
      reliability and known-groups validity of the test. CONCLUSION: The 18-item
      geriatrics knowledge test demonstrated sound reliability and validity. The
      average scores of the student groups indicated substantial room for growth. The
      relationship between geriatrics knowledge and overall clinical skills needs
      further investigation.

PMID- 15161465
TI  - Isokinetic leg muscle strength in older americans and its relationship to a
      standardized walk test: data from the national health and nutrition examination
      survey 1999-2000.
AB  - OBJECTIVES: To describe isokinetic knee extensor muscle strength in older U.S.
      men and women by age and race/ethnicity and to ascertain its relationship to a
      standard, timed walking-speed test. SETTING: The U.S. National Health and
      Nutrition Examination Survey (NHANES) 1999-2000. DESIGN: A cross-sectional
      nationally representative health examination survey. PARTICIPANTS: All surveyed
      persons aged 50 and older (N=1,499) who performed muscle strength and timed walk
      examinations in the NHANES mobile examination center. MEASUREMENTS: Concentric
      peak torque (strength) of the knee extensors at 1.05 rads/ s(-1) velocity and a 6
      m walk timed in seconds. RESULTS: Knee extensor strength was inversely associated
      with age (P<.01), and women had less knee extensor muscle strength than men
      (P<.01). After adjustment for standing height, no significant difference in
      muscle strength was found across the three race/ethnicity groups (Mexican
      Americans, non-Hispanic blacks, and non-Hispanic whites) for men or women. After
      adjustment for age, race/ethnicity, weight, and height, increasing knee extensor
      strength was associated with significant increases in meters walked per second
      (P<.01). CONCLUSION: Knee extensor muscle strength is affected by age and sex but
      not by race/ethnicity and it is significantly associated with timed walk.

PMID- 15161467
TI  - Effects of the balanced budget act on Medicare home health utilization.
AB  - This article examines the effects of the Balanced Budget Act of 1997 on Medicare
      home healthcare utilization by older adults in different income groups. Data are
      drawn from a sample of functionally limited Medicare-eligible elderly respondents
      (N=2,749) from the Medical Expenditures Panel Survey. Results from multivariate
      analyses revealed that, although policies succeeded in curbing home health
      expenditures for all income groups, the reduction was heavily concentrated among
      the poorest respondents. Between 1997 and 1998, Medicare home health expenditures
      decreased by 1,404 dollars in lower income respondents, four times as much as the
      reduction in expenditures in middle-income respondents (352 dollars) and more
      than twice the reduction in high-income respondents (567 dollars). These findings
      raise important questions about whether the decrease in expenditures will result
      in increased incidence of adverse effects or less satisfaction with care of
      vulnerable individuals.

PMID- 15161468
TI  - Recognition of late-life depression in home care: accuracy of the outcome and
      assessment information set.
AB  - This study evaluated the accuracy of home care nurses' ratings of the Outcome and
      Assessment Information Set (OASIS) depression items. The accuracy of home care
      nurses' depression assessments was studied by comparing nurse ratings of OASIS
      depression items with a research diagnostic assessment based on the Structured
      Clinical Interview for Axis I Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (SCID). The setting for this study was a nonprofit,
      Medicare-certified, voluntary home healthcare agency. Sixty-four home care nurses
      assessed 220 patients aged 65 and older with the OASIS upon admission. Of the 220
      patients, using standard SCID criteria, 35 cases of major or minor depression
      were identified. The home care nurses accurately documented the presence of
      depression in 13 of 35 cases (sensitivity=37.1%; positive predictive value=0.56).
      Of the 220 patients, 185 had no SCID-identified major or minor depression. The
      nurses agreed on the absence of depression in 175 of 185 cases
      (specificity=94.6%; negative predictive value=88.8%). This study indicates that
      home care nurses often do not accurately rate OASIS depression items for older
      adult patients.

PMID- 15161469
TI  - Disciplinary split: a threat to geriatrics interdisciplinary team training.
AB  - In 1995, the John A. Hartford Foundation launched an initiative to strengthen
      geriatric interdisciplinary team training (GITT) for advanced practice nursing
      and masters-level social work students and residents in internal medicine and
      family practice. As part of the national evaluation of the initiative, case-study
      and cross-case designs were employed using quantitative and qualitative data to
      examine the influence of cultures, regulations, and attitudes of individual
      disciplines on interdisciplinary training efforts at the first eight GITT
      programs. This evaluation found that attitudinal and cultural traditions of the
      different health professions faculty and students (disciplinary split) remain as
      important obstacles to creating an optimal interdisciplinary team-training
      experience. In general, physician trainees participated least enthusiastically in
      GITT. In part, this lower level of enthusiasm may have been the result of
      inconsistent medicine faculty support of the program. At all but one program,
      physician trainees also had shorter GITT training experiences than other
      disciplines. In addition, the disparity in level of training by discipline of
      GITT participants may have contributed to attitudinal barriers to
      interdisciplinary training. Discipline-specific regulatory and accreditation
      barriers also impede interdisciplinary training. Nevertheless, GITT experiences
      at some clinical sites, especially home visits, appeared to promote
      interdisciplinary training. Some barriers to creating and implementing GITT
      programs may be best approached at the level of accrediting agencies and
      certifying organizations. Others will require local and national efforts of
      leaders in the different disciplines to model and support good team care.

PMID- 15161470
TI  - Adult immunization in university-based primary care and specialty practices.
AB  - The purpose of this study was to assess vaccination status of adults in primary
      and specialty care practices in a retrospective review of medical records from
      1997 to 2000 at one university medical center. Eligible patients were aged 50 and
      older and had two or more visits to primary and specialty care practices
      (N=14,556). Outcomes were receipt of pneumococcal vaccine once, tetanus booster
      within 10 years, and influenza vaccine in 2 of the 3 years. Vaccination rates for
      patients aged 65 and older were 59% for pneumococcal, 51% for tetanus, and 32%
      for influenza. Asians, Latinos, and African Americans were more likely than
      whites to have received influenza, pneumococcal, or tetanus vaccinations.
      Patients seen in primary care (41%) or in both primary care and specialty
      practices (42%) were more likely to receive adequate vaccination than those in
      specialty practices (17%) (P<.001). For pneumococcal vaccinations, relative to
      patients receiving specialty care only, patients receiving primary care only had
      an adjusted odds ratios (OR) of 6.6 (95% confidence interval (CI)=5.6-7.7) and
      patients in both primary care and specialty care had an OR of 7.2 (95% CI=6.2
      8.3). For influenza, the corresponding ORs were 3.9 and 4.8, respectively, and
      for tetanus, 4.6 and 5.2. Patients who received care only from specialty
      practices were less likely than those with some primary care to receive adequate
      adult vaccinations. With the exception of Russian immigrants, the study did not
      find that racial and ethnic minorities had lower rates of vaccination than
      whites.

PMID- 15161471
TI  - The Medicare Prescription Drug, Improvement, and Modernization Act of 2003.

PMID- 15161473
TI  - Interpreting interventions to improve drug use using administrative databases.

PMID- 15161474
TI  - Pain in nursing home residents: what does it really mean, and how can we help?

PMID- 15161475
TI  - Model and systems of geriatric care: "delirium rooms"--but where and at what
      cost?

PMID- 15161479
TI  - End-of-life care and family involvement.

PMID- 15161477
TI  - Delay in nursing home placement with donepezil.

PMID- 15161481
TI  - Polymyalgia rheumatica: can the diagnosis be made in the presence of malignancy?

PMID- 15161482
TI  - Half a purple painful tongue.

PMID- 15161483
TI  - Diagnostic challenge of painful neuropathies in the elderly and the role of sural
      nerve biopsy.

PMID- 15161485
TI  - Depressed involuntary swallowing and risk of pneumonia.

PMID- 15161484
TI  - Polycythemia in a physician secondary to self-administered growth hormone,
      testosterone, and dehydroepiandrosterone to prevent aging.

PMID- 15161486
TI  - Syringomyelia: an uncommon cause of myelopathy in the geriatric population.

PMID- 15161487
TI  - Glycogen storage disease type II diagnosed in a 74-year-old woman.

PMID- 15161488
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy: an unusual familial dementia. Report of a case and review of
      the literature.

PMID- 15161489
TI  - Correlation between pulse wave velocity and cognitive function in nonvascular
      dementia.

PMID- 15161490
TI  - Geriatric training in problem-based learning: an Asian perspective.

PMID- 15161491
TI  - Abdominal pain in an elderly osteoporotic patient: ribs on pelvis syndrome.

PMID- 15161493
TI  - Structure of GlgS from Escherichia coli suggests a role in protein-protein
      interactions.
AB  - BACKGROUND: The Escherichia coli protein GlgS is up-regulated in response to
      starvation stress and its overexpression was shown to stimulate glycogen
      synthesis. RESULTS: We solved the structure of GlgS from E. coli, a member of an
      enterobacterial protein family. The protein structure represents a bundle of
      three alpha-helices with a short hydrophobic helix sandwiched between two long
      amphipathic helices. CONCLUSION: GlgS shows structural homology to Huntingtin,
      elongation factor 3, protein phosphatase 2A, TOR1 motif domains and
      tetratricopeptide repeats, suggesting a possible role in protein-protein
      interactions.

PMID- 15161494
TI  - Sample size and power estimation for studies with health related quality of life
      outcomes: a comparison of four methods using the SF-36.
AB  - We describe and compare four different methods for estimating sample size and
      power, when the primary outcome of the study is a Health Related Quality of Life
      (HRQoL) measure. These methods are: 1. assuming a Normal distribution and
      comparing two means; 2. using a non-parametric method; 3. Whitehead's method
      based on the proportional odds model; 4. the bootstrap. We illustrate the various
      methods, using data from the SF-36. For simplicity this paper deals with studies
      designed to compare the effectiveness (or superiority) of a new treatment
      compared to a standard treatment at a single point in time. The results show that
      if the HRQoL outcome has a limited number of discrete values (< 7) and/or the
      expected proportion of cases at the boundaries is high (scoring 0 or 100), then
      we would recommend using Whitehead's method (Method 3). Alternatively, if the
      HRQoL outcome has a large number of distinct values and the proportion at the
      boundaries is low, then we would recommend using Method 1. If a pilot or
      historical dataset is readily available (to estimate the shape of the
      distribution) then bootstrap simulation (Method 4) based on this data will
      provide a more accurate and reliable sample size estimate than conventional
      methods (Methods 1, 2, or 3). In the absence of a reliable pilot set,
      bootstrapping is not appropriate and conventional methods of sample size
      estimation or simulation will need to be used. Fortunately, with the increasing
      use of HRQoL outcomes in research, historical datasets are becoming more readily
      available. Strictly speaking, our results and conclusions only apply to the SF-36
      outcome measure. Further empirical work is required to see whether these results
      hold true for other HRQoL outcomes. However, the SF-36 has many features in
      common with other HRQoL outcomes: multi-dimensional, ordinal or discrete response
      categories with upper and lower bounds, and skewed distributions, so therefore,
      we believe these results and conclusions using the SF-36 will be appropriate for
      other HRQoL measures.

PMID- 15161496
TI  - [Recent advances in the pathogenesis, diagnosis and treatment of hepatic
      fibrosis].

PMID- 15161495
TI  - Bioinformatics analysis of SARS coronavirus genome polymorphism.
AB  - BACKGROUND: We have compared 38 isolates of the SARS-CoV complete genome. The
      main goal was twofold: first, to analyze and compare nucleotide sequences and to
      identify positions of single nucleotide polymorphism (SNP), insertions and
      deletions, and second, to group them according to sequence similarity, eventually
      pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome
      polymorphism such as insertions or deletions and the number and positions of
      SNPs. RESULTS: The nucleotide structure of all 38 isolates is presented. Based on
      insertions and deletions and dissimilarity due to SNPs, the dataset of all the
      isolates has been qualitatively classified into three groups each having their
      own subgroups. These are the A-group with "regular" isolates (no insertions /
      deletions except for 5' and 3' ends), the B-group of isolates with "long
      insertions", and the C-group of isolates with "many individual" insertions and
      deletions. The isolate with the smallest average number of SNPs, compared to
      other isolates, has been identified (TWH). The density distribution of SNPs,
      insertions and deletions for each group or subgroup, as well as cumulatively for
      all the isolates is also presented, along with the gene map for TWH. Since
      individual SNPs may have occurred at random, positions corresponding to multiple
      SNPs (occurring in two or more isolates) are identified and presented. This
      result revises some previous results of a similar type. Amino acid changes caused
      by multiple SNPs are also identified (for the annotated sequences, as well as
      presupposed amino acid changes for non-annotated ones). Exact SNP positions for
      the isolates in each group or subgroup are presented. Finally, a phylogenetic
      tree for the SARS-CoV isolates has been produced using the CLUSTALW program,
      showing high compatibility with former qualitative classification. CONCLUSIONS:
      The comparative study of SARS-CoV isolates provides essential information for
      genome polymorphism, indication of strain differences and variants evolution. It
      may help with the development of effective treatment.

PMID- 15161497
TI  - [Expression of CCAAT/enhancer-binding protein in cultured rat hepatic stellate
      cells and its significance].
AB  - OBJECTIVE: The expression of C/EBPalpha protein and mRNA during automatically
      activation process in primary cultures of HSCs were observed in order to explore
      its possible association with the proliferation and activation of HSCs. METHODS:
      Immunocytochemistry, Western blot and RT-PCR were used to evaluated the
      expression of C/EBPalpha protein and mRNA; as well as the expression of alpha
      SMA, Desmin, MMP2, type I procollagen (alpha1). The eukaryotic vector harboring
      the full length cDNA of C/EBPalpha was transfected into activated HSC, then
      immunocytochemistry was applied to confirm the transfection and evaluate the
      effect of transfection on the proliferation of HSC by calculating the PCNA
      positive cells. The morphological changes of HSC were observed by use of phase
      contrast microscope. RESULTS: Constitutive expression of mRNA and protein of
      C/EBPalpha were detected in primarily cultured HSCs, and the protein was seen in
      both nuclei and cytoplasm with the latter being dominant. Their expression levels
      reached highest at day 2 of the culture, then decreased gradually when
      continually cultured to the day 4, 7, 10, on the other hand, the expression of
      alpha-SMA, MMP2 and ColI(alpha1) increased steadily. Transient transfection was
      verified by the fact that much more and stronger C/EBPalpha stain was observed in
      transfected HSCs than in void-vector transfected cells. In C/EBPalpha gene
      transfected HSCs, the number of PCNA-positive cells dramatically decreased
      compared with the void-vector transfected cells 24h after transfection. In
      addition, the C/EBPalpha gene transfected HSCs died 36 h after transfection, a
      few surviving cells became longer and thinner in morphology, however the void
      vector transfected cells almost all remained alive. CONCLUSIONS: C/EBPalpha was
      likely involved in the HSCs activation, and over-expressed C/EBPalpha by
      transfection had inhibitory influence on the proliferation of cultured rat HSCs.

PMID- 15161498
TI  - [Obstruction of TGF-beta1 signal transduction by anti-Smad4 gene can therapy
      experimental liver fibrosis in the rat].
AB  - OBJECTIVE: To study the therapeutic effects to block the TGF-beta1 (transforming
      growth factor beta1) signal transduction by antisense Smad4 gene on experimental
      fibrotic liver. METHODS: Using the rat model of liver fibrosis induced by Carbon
      Tetrachloride (CCl4)/ethanol, we transfected antisense Smad4 gene mediated by
      adenovirus via portal vein infusion into the liver, and observed the expression
      of Smad4 by Retro-Polymerase Chain Reaction (RT-PCR) and Western Blot. We also
      investigated the pathologic features and collagen expression. RESULTS: In the non
      therapeutic cirrhotic liver, the expression of Smad4 mRNA was significantly
      increased than normal liver, and so was the collagen I. After antisense Smad4
      gene being transfected, the expression of Smad4 mRNA and that of collagen I in
      the therapeutic liver was significantly decreased, compared with the non
      therapeutic cirrhotic liver. The fibrous degree of therapeutic liver was also
      reduced compared with the non-therapeutic fibrous liver. CONCLUSION: These
      results indicate that because antisense Smad4 gene could block TGF-beta1 signal
      transduction by reducing the expression of Smad4, so it could inhibit the
      production of extracellular matrix (ECM) and improve hepatic fibrosis.

PMID- 15161499
TI  - [The role of changes of MMP-2, 9 activity in the development of liver fibrosis in
      rats].
AB  - OBJECTIVE: To study the role of changes of matrix metalloproteinase-2, 9 (MMP-2,
      9) activity in the development of dimethylnitrosamine (DMN)-induced liver
      fibrosis in rats. METHODS: The rat liver fibrosis model was established by
      peritoneal injection of DMN (at a dose of 10 mg/kg, 3 times a week, for 4 weeks).
      The dynamic changes of liver fibrosis were observed at different time points (1d,
      2d, 3d, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks). The MMP-2, 9 activity was
      measured by zymogram method. Liver ultrastructure was observed by electron
      microscope. The expressions of type IV collagen (CIV), laminin (LN), type I
      collagen (CI) and alpha-smooth muscle actin (alpha-SMA) were examined by
      immunohistochemistry. The tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)
      content was measured by Western blot method. RESULTS: The MMP-2, 9 activity (gray
      value) significantly increased in the 2d and 3d DMN model rats (2d: normal/model
      group, MMP-2: 54.72+/-4.56/70.76+/-7.63; F = 16.27, P < 0.05; MMP-9: 25.72+/
      4.29/51.76+/-15.33, F=13.38, P < 0.05). The positive staining area percentage of
      CIV in the sinusoidal walls decreased in the 2d, 3d and 1 weeks model rats (2d:
      normal/model group, 6.06+/-1.35/2.86+/-0.63, F=69.12, P < 0.05), but
      significantly increased in the 4w model rats (normal/model group, 6.06+/
      1.35/8.04+/-1.50, F=14.42, P < 0.05). There was a remarkable negative correlation
      between the MMP-9 activity and expression of CIV in the sinusoidal walls (r = 
      0.729, P < 0.05). Positive expressions of LN and CI increased, and the strongest
      positive staining of them displayed in the 4w model rats. The formation of
      basement membrane was also observed in the 4 weeks model rats. Expression of TIMP
      2 significantly increased in the late stage of fibrosis. CONCLUSIONS: The
      increase of MMPs activity, especially MMP-9 which degrades the CIV normally
      distributed under the sinusoidal endothelium is the important factor in the
      formation of sinusoidal capillarization. The deposition and reconstitution of LN
      and new synthetic CIV, adding the deposition of CI constitute the high density
      basement membrane. The increase of TIMP-2 expression in the late stage of the
      fibrosis may be one of reasons why natural resolution of DMN-induced liver
      fibrosis is difficult.

PMID- 15161500
TI  - [The relationship between hepatic expression, serum level of TGFbeta1 and the
      hepatic fibrosis in patients with viral hepatitis].
AB  - OBJECTIVE: To detect the hepatic tissue and serum level of TGFbeta1 in patients
      with viral hepatitis, in order to clarify their relationship of the starting,
      developing of hepatic fibrosis. METHODS: This study included 92 patients with
      viral hepatitis. Liver puncture was performed in 31 patients. Hepatic collagen
      staining (Masson's three colors) and TGFbeta1 immunohistochemistry staining of
      the liver tissue specimens were performed, morphometric quantitative measurements
      of hepatic histological collagen and TGFbeta1 were made. The serum level of
      TGFFbeta1 was detected by ELISA. RESULTS: The surface density of hepatic TGFbeta1
      increased linearly with the elevation of fibrosis stage (P < 0.05), there were no
      significant differences between every two groups of G1, G2, G3 and G4 (P >
      0.005). There was a closely positive correlation between the levels of TGFbeta1
      in hepatic tissue and serum, the coefficient was 0.896 (P < 0.01). The levels of
      TGFbeta1 in tissue and serum both had positive correlation with hepatic collagen,
      coefficients were 0.863 and 0.667 (P < 0.001). The level of TGFbeta1 in tissue
      and serum both had positive correlation with serum levels of PCIII, HA, LN, CIV
      (P < 0.001). CONCLUSIONS: There was a closely relationship between the levels of
      TGFbeta1 in hepatic tissue and serum and liver fibrosis. The detection of
      TGFbeta1 in liver and serum are more sensitive than HA, LN, CIV in early period
      of hepatic fibrosis.

PMID- 15161501
TI  - [Frequency and function decrease of circulating type 2 pre-dendritic cells (pDC2)
      and its clinical significance in liver cirrhotic patients with chronic HBV
      infection].
AB  - OBJECTIVE: To identify the frequency and interferon (IFN)-alpha-producing ability
      of circulating type 2 pre-dendritic cells (pDC2) and evaluate its role in liver
      cirrhotic patients with chronic HBV infection. METHODS: 27 liver cirrhotic
      patients were included in our study and 25 patients with chronic hepatitis B and
      25 healthy individuals were enrolled as controls. The numbers of circulating pDC2
      and lymphocytes including CD4+ T cells, CD8+ T cells, NK cells as well as B cells
      were analyzed by flow cytometry. The IFN-alpha-producing function of peripheral
      blood mononuclear cells (PBMCs) representing the circulating pDC2 was determined
      by ELISA assay after stimulated by ultraviolet-inactivated herpes simplex virus-1
      (UV-HSV-1). RESULTS: The number of pDC2 were (7.21+/-2.38)*10(6)/L, (4.49+/-3.08)
      *10(6)/L and (2.89+/-1.17) *10(6)/L for healthy control, chronic hepatitis B and
      cirrhotic patients respectively. Both the number and IFN-alpha-producing function
      of circulating pDC2 in liver cirrhotic patients significantly lower than that in
      healthy subjects. There was a correlated simultaneous decrease numbers of
      circulating CD8+ T cells, NK cells in HBV-infected cirrhotic patients.
      Furthermore, cirrhotic patients with opportunistic infections have lower numbers
      of pDC2, CD8+ T cells and NK cells compared to those without opportunistic
      infections. CONCLUSIONS: Liver cirrhotic patients with chronic HBV infection have
      a significant decrease of circulating pDC2 level and IFN-alpha-producing
      function. The decreased number and function of pDC2, together with the lower
      number of CD8+ T cells and NK cells may result in the decline of host immune
      response, which may partially contribute to the disease progression of HBV
      infection and opportunistic infections.

PMID- 15161502
TI  - [Clinical study of renal blood flow and endothelin in cirrhotic patients].
AB  - OBJECTIVES: To find the relationship between hepatic dysfunction and renal blood
      flow (RBF). METHODS: 49 patients with hepatic cirrhosis were studied via Color
      Coded Duplex Ultrasonography detecting the pulsatile index (PI), resistive index
      (RI), peak systolic velocity (PS), peak diastolic velocity (PD) and peak systolic
      velocity/peak diastolic velocity (PS/PD) in the interlobar and arcuate arteries.
      The plasma endothelin (ET) levels were also evaluated. RESULTS: According to a
      modified Child's classification which assesses the severity of liver cirrhosis,
      we compared different groups and found that the worse the function of liver
      appeared coincidently with the higher PI and RI, especially RI (0.60+/-0.09,
      0.66+/-0.06, 0.72+/-0.07, respectively, P < 0.01); The results also indicated
      that PI, RI increased obviously followed by the rise of ascites (PI: 1.14+/-0.20,
      1.31+/-0.29, 1.42+/-0.36, respectively; RI: 0.61+/-0.09, 0.68+/-0.07, 0.77+/
      0.05, respectively). The evaluation of plasma ET level demonstrated that its
      increment is intimately correlated with PI and RI. CONCLUSION: In patients with
      cirrhosis, RBF is directly correlated with the hepatic function. The correlation
      between ascites and RBF is also discovered. In patients who have liver cirrhosis,
      the plasma ET level obviously increased, indicating that ET probably is one of
      the active factors of renal vascular contraction.

PMID- 15161503
TI  - [A study on relationship between CT grouping and complication of liver
      cirrhosis].
AB  - OBJECTIVES: To probe into the relationship between the CT grouping of liver
      cirrhosis and its complications as well as clinical condition. METHODS: On the
      basis of CT findings in 357 cases with liver cirrhosis, CT grouping of the
      cirrhosis was performed. The complications of the cirrhosis, including
      enlargement of spleen, varicose collateral veins, ascites, pleurorrhea, primary
      liver carcinoma, gallbladder stone, etc, of all groups were analyzed. According
      to examination the blood routine, and the serum urea nitrogen (SUN), creatinine
      and uric acid, the condition of spleen function accentuation and liver-kidney
      syndrome were estimated. RESULTS: Three hundred and fifty-seven cases with
      cirrhosis were divided into homogeneous group (87 cases, 24.4%), segmental group
      (41 cases, 11.5%) and nodal group (229 cases, 64.1%). The grade of spleen
      enlargement in the segmental group and the nodal group was significantly greater
      than that in homogeneous group. The cases with varicose in the segmental group
      was the most (70.7%), in the nodal group next (17.0%) and in the homogeneous
      group the least (2.3%). There was significant difference among three groups. In
      the nodal group, there was ascites in 182 cases (79.5%) and significantly more
      than that in the segmental group (11 cases, 26.8%) and the homogeneous group (9
      cases, 10.3%), and the former significantly more than the latter. There were 68
      cases (29.7%) with primary liver carcinoma in the nodal group, and significantly
      more than that in the segmental group (1 case, 2.4%) and the homogeneous group (5
      cases, 5.7%). The cases with hemoglobin decrease in the nodal group were
      significantly more than that in the homogeneous group. The averages of hemoglobin
      and platelet in the nodal group and the segmental group were significantly lower
      than that in the homogeneous group. The cases with SUN increase in the nodal
      group and the segmental group were significantly more than that in the
      homogeneous group. The concentration of SUN in the nodal group was significantly
      higher than that in the homogeneous group. CONCLUSIONS: There are close
      relationship between the grouping of liver cirrhosis on basis of CT findings and
      complications of the cirrhosis. The practice of grouping might be useful for
      estimating clinical condition

PMID- 15161504
TI  - [Involvement of TRAIL up-regulation of CD4+, CD8+ T cells in liver injury in
      chronic hepatitis B].
AB  - OBJECTIVE: To describe a novel mechanism for TRAIL up-regulation of CD4+, CD8+ T
      cells to participate in the pathophysiological process in patients with chronic
      hepatitis B (CHB). METHODS: The serum levels of soluble TRAIL (sTRAIL), 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 15 healthy controls, and correlation
      analysis were performed between ALT, TBil and PT, morphological change in hepatic
      tissues. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+
      T cells in CHB patients were much higher than the healthy controls (P < 0.001),
      which of CD4+ T cells positively correlated with serum TBil (r=0.354, P = 0.008),
      Serum IFN-gamma level (r=0.302, P = 0.011) and which of CD8+ T cells positively
      correlated with serum TBil (r=0.522, P = 0.000), ALT (r=0.393, P = 0.003), PT
      (r=0.385, P = 0.004), serum IFN-gamma level (r=0.307, P = 0.009). The serum
      levels of soluble TRAIL only correlated with serum HBeAg expression (r=0.695, P =
      0.001). CONCLUSION: These findings suggest that the expression of TRAIL on the
      membranes of lymphocytes was up-regulated, which may take part in the
      immunopathogenesis in CHB patients. TRAIL expression can be induced either by
      virus-specific protein expression or by inflammation cytokine IFN-gamma

PMID- 15161505
TI  - [Expression and clinical significance of HBsAg and HBcAg in hepatocytes in
      chronic hepatitis B].
AB  - OBJECTIVE: To study the expression of HBsAg and HBcAg in hepatocytes in CHB
      patients, and analyze the correlation among the expression of HBsAg and HBcAg,
      the quantity of HBV DNA in serum, the pathology of liver tissue and the clinical
      manifestation. METHODS: Quantitative polymerase chain reaction was used to assay
      the quantity of HBV DNA in serum in 351 CHB patients. Furthermore pathological
      diagnosis was performed using liver biopsy to assay the expression of HBsAg and
      HBcAg in hepatocytes by an immunohistochemical staining technique. RESULTS: The
      positive expression rate of HBsAg and HBcAg in hepatocytes was 92.3% and 76.9%
      respectively. Cytoplasm-membrane HBcAg expression type (75.6%) was observed in
      the CHB with more active inflammation, while Nucleus HBcAg expression type
      (24.4%) was observed in the CHB with more sedative one (P < 0.0001). The
      expression of HBsAg was correlated with the quantity of HBV DNA in serum (rp =
      0.24, P = 0.0129), while inversely correlated with the inflammation and the
      fibrillation of liver tissue (rp = -0.22, P = 0.0279; rp = -0.23, P = 0.0186).
      The expression of HBcAg was correlated with the quantity of HBV DNA in serum (rp
      = 0.52, P < 0.0001), while was inversely correlated with the inflammation and the
      fibrosis of liver (rp = -0.33, P < 0.0001; rp = -0.34, P < 0.0001). CONCLUSION:
      Cytoplasm-membrane HBcAg expression type was observed in the CHB with more active
      inflammation, while Nucleus HBcAg expression type was observed in the CHB with
      mild change. In the immunopathogenesis of the liver damage in CHB, HBcAg might be
      a main target antigen. HBsAg might be a sensitive index to screen HBV infection;
      HBcAg might probably be a reliable index to evaluate the replication of HBV

PMID- 15161507
TI  - [The effect of artificial support system on serum cytokine in chronic severe
      hepatitis].
AB  - OBJECTIVE: To explore the changes of cytokines including TNFalpha, TGFbeta1 and
      nitrogen monoxide, and endotoxin in the serum of chronic severe hepatitis after
      the treatment of ALSS, and to evaluate further the value of ALSS in the treatment
      of chronic severe hepatitis. METHODS: Forty two patients were screened. The
      changes of TNFalpha, TGFbeta1, nitrogen monoxide and endotoxin were detected
      respectively. The relationship between the cytokines and the severity and
      prognosis were further analyzed. RESULTS: ALSS was effective to decrease the
      serum concentration of cytokines. TNFalpha dropped from (481.57+/-229.33) pg/ml
      to (156.46+/-78.12) pg/ml (P < 0.05). TGFbeta1 from (44.09+/-31.73) ng/ml to
      (27.77+/-23.28) ng/ml (P < 0.01), endotoxin from (1.05+/-0.37) Eu/ml to (0.28+/
      0.22) Eu/ml (P < 0.001). NO from (71.15+/-33.09) micromol/L to (58.11+/-29.30)
      micromol/L (P < 0.001). Before the therapy endotoxin was related with TNFalpha
      and total bilirubin, while after the therapy, NO was related with protime and
      aminonemia. CONCLUSION: High level of endotoxin and nitrogen monoxide in serum
      plays an important role in hepatocyte damage of chronic severe hepatitis. The
      changes of serum endotoxin TNFalpha, TGFbeta1 and nitrogen monoxide level in
      patients with chronic severe hepatitis can be used to judge the severity and
      prognosis of severe hepatitis. ALSS is a reliable hepatic support device for
      chronic severe hepatitis

PMID- 15161506
TI  - [The anti-HBV effect and mechanism of C gene truncated mutant in vitro].
AB  - OBJECTIVE: To explore the effect and mechanism on HBV replication in C gene
      truncated mutant. METHODS: Protein expression of C gene truncated vector and wild
      C gene vector were assay by SDS-PAGE Western blot. Constructed C gene truncated
      expression vector was cotransfected with wild HBV genome; virus load was detected
      by PCR in the culture medium and the cell. The formation of core particle was
      assay by Native western blot. RESULTS: The recombinant vectors can efficiently
      express. Virus load of the cotransfected group by pcDNA3-deltaC and adwR9 was
      lower than that of control group in the culture medium and the cell. Protein band
      of the co-expressed group by pcDNA3-deltaC and pcDNA3-C showed slightly weaker
      than that of the co-expressed group by pcDNA3 and pcDNA3-C. CONCLUSION: C gene
      truncated mutant could interfere with the formation of core particle and reduce
      of HBV replication

PMID- 15161508
TI  - [Cytokine gene polymorphisms in Chinese patients with type I autoimmune
      hepatitis].
AB  - OBJECTIVE: To assess the role of Tumor necrosis factor alpha (TNF-alpha) and
      interleukin 10 (IL-10) gene polymorphisms in susceptibility to type I autoimmune
      hepatitis (AIH). METHODS: We detected 2 polymorphisms in TNF-alpha promoter gene
      at positions -238 and -308 and 3 polymorphic sites in IL-10 gene promoter at
      positions -1082, -819, -592 by polymerase chain reaction and dot blot with probes
      in the patients with 32 type I AIH and 48 health controls. RESULTS: Genotypes
      associated with guanine to adenine substitution at position -308 of TNF-alpha
      promoter gene occurred more commonly in the patients than in health controls
      (53.1% vs. 27.1%, RR = 3.05, P < 0.01). There is no significant difference in
      polymorphisms of TNF-alpha gene at position -238 and 3 polymorphic sites in IL-10
      promoter gene between patients and health controls. CONCLUSION: Genotypes
      associated with guanine to adenine substitution at position -308 of TNF-alpha
      promoter gene (TNF-308A) may involve in the pathogenesis of type I AIH

PMID- 15161509
TI  - [The difference between the positive rate of anti-HCV in the patients with severe
      viral hepatitis detected by the first generation or second generation enzyme
      linked-immunosorbent assay].
AB  - OBJECTIVE: To compare the positive rate of antibody to hepatitis C virus (anti
      HCV) in sera of patients with severe viral hepatitis between 1984-1990 year and
      1997-2003 year. METHODS: Serum anti-HCV was detected by enzyme linked
      immunosorbent assay (ELISA). It was detected by the first generation (1st) ELISA
      (Ortho Co. USA) in 79 cases of severe viral hepatitis during 1984-1990 year, and
      it was detected by the second generation (2nd) ELISA (Xiamen Xingchuang Co.
      China) in 251 cases of severe viral hepatitis during 1997-2003 year. RESULTS: The
      positive rate of serum anti-HCV was 51.9% detected by the 1st ELISA in 79 cases
      of severe viral hepatitis during 1984-1990 year, and it was 1.2% detected by the
      2nd ELISA in 251 cases of severe hepatitis during 1997-2003 year (chi2 = 133.68,
      P </= 0.001). CONCLUSION: To compare with the positive rate of serum antibody to
      hepatitis C virus in severe viral hepatitis detected by the 1st ELISA, it was
      lower that detected by the 2nd ELISA

PMID- 15161510
TI  - [Rapid detection of the genotyping of hepatitis C virus using DNA chip with
      coloration methods].
AB  - OBJECTIVE: To develop a new DNA chip with coloration, which can be used for rapid
      and economical detection of the genotyping of hepatitis C virus (HCV). METHODS:
      Probes and primers were designed according to the sequence of HCV 5' non-coding
      region (5' NCR) to fabricate DNA chip. Experimental group consisted of 60
      positive serum samples and control group consisted of 20 negative serum samples.
      To obtain the aimed gene, then they were hybridized with DNA chip. Finally, the
      results showed in a nylon film. The results of DNA sequencing of samples were
      used as the control in double blind experimental. RESULTS: Using DNA chip, HCV
      was detected in positive of all serum specimens of experimental group and
      negative in control group. The determination of HCV genotype by DNA chip showed
      corresponding rate of 96.7% with those by sequence assay. CONCLUSION: It showed
      higher specialty and sensitivity using DNA chip to detect the genotype of HCV. It
      would be valuable for the clinical genotyping of HCV

PMID- 15161511
TI  - [Copper metabolism after living related liver transplantation for Wilson's
      disease].

PMID- 15161513
TI  - [The definition, nomenclature and diagnosis of hepatic encephalopathy].

PMID- 15161512
TI  - [Pathogenesis of hepatic encephalopathy].

PMID- 15161514
TI  - [Therapy for hepatic encephalopathy].

PMID- 15161515
TI  - [The effects of Zuogui Pill on expression of TGF-alpha, beta and it's receptor in
      ARN and regenerative liver of the MSG-regeneration-rat].

PMID- 15161516
TI  - [Effect of aldosterone on the collagen synthesis and TIMP-1 mRNA level in
      cultured rat hepatic stellate cells].

PMID- 15161518
TI  - [The correlation analysis of telomerase activity and aberrant expression of
      telomerase subunits during the progression of hepatocellular carcinoma].

PMID- 15161517
TI  - [Effects of B7-2 on the specific immunity induced by human hepatocellular
      carcinoma].

PMID- 15161519
TI  - [The serum levels of TNF-alpha, IFN-beta, IL-12 in patients with hepatitis B].

PMID- 15161520
TI  - [The correlation of serum DNA level of the chronic hepatitis B and the clinical
      significance].

PMID- 15161522
TI  - [Treatment of severe hepatitis by artificial liver support system].

PMID- 15161521
TI  - [Closed extra corporal concentration and reinfusion of ascites in cirrhosis of
      liver patients with refractory ascites].

PMID- 15161523
TI  - [The protective effect of reduced glutathione and oxygen persufflation on rat
      steatotic grafts following transplantation].

PMID- 15161525
TI  - [The evolution and characteristics of liver function classification: from Child
      to MELD].

PMID- 15161524
TI  - [The application of gene chip in the diagnosis and treatment of hepatocellular
      carcinoma].

PMID- 15161526
TI  - Effects of Losartan on acute atrial electrical remodeling.
AB  - BACKGROUND: Atrial electrical remodeling (AER) contributes to the maintainance of
      atrial fibrillation (AF). This study was to compare the effects of Losartan with
      those of Diltiazem on tachycardia-induced acute AER in rabbits. METHODS: Twenty
      one rabbits paced with maximal atrial capture rate for 3 hours in the right
      atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan
      group. After autonomic blockage, we measured atrial effective refractory period
      (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at
      basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0.5 hour, 1 hour, 2
      and 3 hours after rapid atrial pacing. RESULTS: In the saline group, there was a
      prompt decrease in AERP as a result of rapid atrial pacing, and AERP200 and
      AERP150 were shortened sharply within 0.5 hour of pacing (30.2 +/- 10.5 ms and
      24.1 +/- 9.1 ms, respectively). The AERP did not change dramatically in the
      Diltiazem and Losartan groups. In the saline group, the value of (AERP200
      AERP150)/50 ms in high RA was 0.17 +/- 0.08 at baseline and became significantly
      smaller at 0.5 hour (0.08 +/- 0.06), 1 hour (0.09 +/- 0.06), 2 hours (0.08 +/-
      0.04) and 3 hours (0.09 +/- 0.05) (all P < 0.05), suggesting a reduction of rate
      adaptation of AERP. The value of (AERP200-AERP150)/50 ms in high RA did not
      change during the 3 hours of pacing in both Diltiazem and Losartan groups. In the
      saline group, AERP dispersion increased significantly at 2 and 3 hours (P <
      0.05). However, Diltiazem could not prevent the increase of AERP dispersion at 3
      hours (P < 0.05). During Losartan infusion, the AERP dispersion was no longer
      increased after rapid atrial pacing. There was no significant difference in RA
      conduction time among the three groups. CONCLUSION: Like calcium antagonist
      Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of
      AERP after rapid atrial pacing. Losartan is more effective than Diltiazem in
      inhibiting the increase of AERP dispersion.

PMID- 15161527
TI  - Cardioprotective effects of mitochondrial KATP channels activated at different
      time.
AB  - BACKGROUND: Recent studies in adult hearts have indicated that KATP channels in
      the inner mitochondrial membrane are responsible for the protection. And we
      investigated whether opening of mitochondrial KATP channels (mKATP) could provide
      myocardial protection for immature rabbits and determined its role in
      cardioprotection. METHODS: Thirty-four 3-4-week-old rabbits, weighing 300 - 350
      g, were divided randomly into five groups: Group I (control group, n = 8); Group
      II [diazoxide preconditioning group; n = 8; the hearts were pretreated with 100
      micromol/L diazoxide for 5 minutes followed by 10-minute wash out with Krebs
      Henseleit buffer (KHB)]; Group III [diazoxide + 5-hydroxydeconate (5-HD)
      preconditioning group; n = 5; the hearts were pretreated with 100 micromol/L
      diazoxide and 100 micromol/L 5-HD); Group IV (diazoxide + cardioplegia group; n =
      8; cardioplegia containing 100 micromol/L diazoxide perfused the hearts for 5
      minutes before ischemia); Group V (diazoxide + 5-HD + cardioplegia group; n = 5;
      the cardioplegia contained 100 micromol/L diazoxide and 100 micro mol/L 5-HD).
      All hearts were excised and connected to langendrff perfusion system and
      passively perfused with KHB at 38 degrees C under a pressure of 70 cmH(2)O. After
      reperfusion, the recovery rate of left ventricular diastolic pressure (LVDP), +/
      dp/dtmax, coronary flow (CF), the creatinine kinase (CK), lactate dehydrogenase
      (LDH), aspartate aminotransferase (AST) in coronary sinus venous effluent and the
      tissue ATP were measured. Mitochondria were evaluated semiquantitatively by
      morphology. RESULTS: After ischemia and reperfusion (I/R), the two groups that
      were treated by diazoxide only (Groups II and IV) had a significant improvement
      in LVDP, +/-dp/dtmax, and CF recovery. AST, LDH, and CK were decreased, and the
      levels of tissue ATP in the two groups were higher. Mitochondria was protected
      better in Group IV than in other groups. CONCLUSIONS: Activating mKATP channels
      before and during ischemia can similarly protect immature rabbit hearts, and the
      mechanism is related to the direct protective effect on mitochondria. Opening of
      mKATP channel during ischemia provides a better protection for mitochondria than
      it does before ischemia.

PMID- 15161529
TI  - Survey of children with obstructive sleep apnea syndrome in Hong Kong of China.
AB  - BACKGROUND: Obstructive sleep apnea affects up to 2.9% of children. This study
      was to determine demographic and clinical characteristics of a group of children
      with obstructive sleep apnea syndrome (OSAS) as defined by sleep polysomnography
      (PSG). METHODS: A prospective study was conducted in a public-funded general
      hospital in Hong Kong of China. Children confirmed to have OSAS by PSG were
      followed up between January 1997 and December 1998. Tonsillectomy and
      adenoidectomy (T&A) was offered to those with moderate to severe OSAS, and
      medication was offered to those with mild OSAS. All children were followed up
      regularly in the sleep clinic and sleep PSG was repeated for those with marked
      relapse in symptoms. RESULTS: Eighty-nine children (64 boys and 25 girls, mean
      age 7 years) were confirmed to have OSAS out of 352 children who underwent PSG
      during the study period. The most common symptoms of OSAS were snoring (100%) and
      sweating (81%) during sleep and nasal blockage (61%) and sleepiness (34%) during
      daytime. Severe OSAS occurred in 15 children. Moderate OSAS occurred in 33
      children. Forty-one children had mild OSAS. Forty-nine children underwent T&A, 5
      (boys, < 5 years) out of whom were found to have recurrent OSAS within 1 year.
      CONCLUSION: A male predominance has been found in a group of Hong Kong children
      with OSAS. Boys undergoing T&A at an early age (< 5 years) will be more likely to
      develop repeated OSAS.

PMID- 15161528
TI  - Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their
      relation with Brugada syndrome.
AB  - BACKGROUND: Mutations in the cardiac sodium channel gene (SCN5A) may lead to a
      broad spectrum of familial arrhythmias, including long QT syndrome (LQTS),
      idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction
      diseases. Recent studies have shown that polymorphisms in the SCN5A gene also
      play an important role in the manifestation of disorders involving cardiac
      excitability. In this study, we investigated the polymorphisms of the SCN5A gene
      in Han Chinese and its relation to Brugada syndrome (BS). METHODS: Genomic DNA
      was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada
      syndrome patients by means of standard procedures. All exons including the
      putative splicing sites of the SCN5A gene were amplified by PCR and sequenced
      directly or after subcloning using an ABI Prism 377 DNA sequencer. RESULTS: A
      total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han
      Chinese population, including 3 novel ones: G87A(A29A), 4245 + 82A > G, and
      G6174A. The allele frequencies of each SNP in the Han Chinese population were as
      follows: G87A (A29A) 27.5%, A1673G (H558R) 10.4%, 4245 + 82A > G 32.8%, C5457T
      (D1819D) 41.3%, and G6174A 44.9%. S1102Y and 10 other SNPs identified in other
      ethnic populations were not detected in this study. There was no significant
      difference in the allele frequency of A1673G (H558R) between different ethnic
      populations (all P > 0.5). On the other hand, the allele frequency of C5457T
      (D1819D) among Han Chinese was similar to its frequency among Japanese (P > 0.5),
      but higher than that among Americans (P < 0.005). The allele G1673 (R558) was
      over-represented in BS patients compared to controls (P < 0.005), but there was
      no significant difference in genotype frequencies at this locus. There were also
      no differences in either the allele or genotype frequencies of the 4 other
      identified SNPs when comparing BS patients with healthy controls. CONCLUSIONS:
      The distribution of SCN5A SNPs may vary between different ethnicities. The
      polymorphism of A1673G might be associated with BS and may contribute to a
      susceptibility to BS in Han Chinese.

PMID- 15161530
TI  - Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase
      and glutathione S-transferase P1 and chronic obstructive pulmonary disease.
AB  - BACKGROUND: Cigarette smoking is the major risk factor for chronic obstructive
      pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette
      smokers develop symptomatic disease. COPD is most likely the result of complex
      interactions between environmental and genetic factors. Genetic susceptibility to
      COPD might depend on the variations in enzyme activities that detoxify cigarette
      smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S
      transferase (GST). In this study, we investigated the relationship between
      polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1)
      and COPD in a Chinese population. METHODS: Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in
      exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5
      (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy
      controls. RESULTS: The proportion of mEH exon 3 heterozygotes was significantly
      higher in patients with COPD than that in the control subjects (42% vs 32%). The
      odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years
      was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow
      activity genotype versus other genotypes between COPD patients and the controls.
      When COPD patients were non-smokers, the OR of very slow activity genotype versus
      other genotypes was more than 1.00; and when COPD patients were smokers (current
      smokers and ex-smokers), the OR was less than 1.00. There was no significant
      difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between
      COPD patients and the controls. CONCLUSIONS: mEH exon 3 heterozygotes might be
      associated with susceptibility to COPD in China. The interaction might exist
      between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be
      associated with susceptibility to COPD in the Chinese population.

PMID- 15161531
TI  - Endogenous erythroid colony assay in patients with polycythemia vera and its
      clinical significance.
AB  - BACKGROUND: Polycythemia vera (PV) is a malignant disorder of hemaopoietic stem
      cells which is characterized by clonal hyperproliferation and a low rate of
      apoptosis. This study was to assess endogenous erythroid colony (EEC) formation
      in the bone marrow of PV patients and determine its clinical significance.
      METHODS: The bone marrow mononuclear cells of 26 patients with PV, 2 patients
      with secondary erythrocytosis (SE), and 19 normal controls were cultured by
      Marsh's method for EEC evaluation, and the clinical significance was evaluated.
      RESULTS: EECs appeared in 25 patients with PV but not in 2 patients with SE and
      19 normal controls. The number of EECs and the EEC ratio [EEC/erythropoietin
      (EPO)-dependent colony forming unit-erythroid (CFU-E)] in PV patients positively
      correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with
      white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline
      phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels.
      Fifteen patients with PV were treated with hydroxyurea (Hu) and/or interferon
      alpha (IFN-alpha). Their EEC ratio before treatment positively correlated with
      the treatment time required for complete remission (CR) and negatively correlated
      with the time before relapse. The EEC numbers of 7 PV patients treated with
      Hu/IFN-alpha decreased after the blood cell counts dropped to normal levels.
      There was a positive correlation between the EEC ratio and the incidence of
      attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone
      marrow mononuclear cells in PV patients were lower than those in normal controls.
      The EEC numbers of PV patients negatively correlated with the rate of apoptosis
      of bone marrow mononuclear cells. CONCLUSIONS: EEC formation is characteristic in
      PV patients. EEC number in PV patients positively correlates with Hb levels, the
      time required for CR, and the incidence of attacks of vascular thrombosis. EEC
      number negatively correlates with the time before relapse. Bone marrow
      suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive
      and specific parameter reflecting the abnormal hematopoietic clone burden induced
      by polycythemia vera. EEC number is an important diagnostic parameter for PV
      patients.

PMID- 15161532
TI  - Major hepatectomy without blood transfusion: report of 51 cases.
AB  - BACKGROUND: Blood transfusion has been found to be a devastating factor for
      outcomes of hepatectomy. This study was to assess the value of major hepatectomy
      without blood transfusion. METHODS: We retrospectively studied 51 patients who
      had undergone major hepatectomy without blood transfusion, including 29 patients
      with primary liver cancer, from August 1997 to December 2000. Sixty patients
      undergoing major hepatectomy with blood transfusion including 48 patients with
      primary liver cancer served as controls. Hepatectomy was performed through
      normothermic interruption of the porta hepatis. Intraoperative ultrasonography
      was performed to define tumor margins, and an ultrasound dissector was used to
      dissect liver parenchyma. RESULTS: In the study group, the operative mortality
      and morbidity and 1-, 2-, and 3-year recurrence rates were 0%, 9.8%, 24.1%, 27.6%
      and 31.0%, respectively. In the control group, they were 3.3%, 28.3%, 43.5%,
      54.3% and 58.7%, respectively. Significant differences were seen in morbidity and
      recurrence rates of patients with liver cancer between the two groups (P < 0.05).
      CONCLUSION: Major hepatectomy without blood transfusion can reduce postoperative
      morbidity and recurrence rate of patients with liver cancer.

PMID- 15161533
TI  - Depression among elderly Chinese-Canadian immigrants from Mainland China.
AB  - BACKGROUND: This study examined the prevalence of depressive symptoms among
      elderly immigrants from Mainland China to Canada and the impact of various
      psychosocial factors as predictors of the number of depressive symptoms reported
      by the elderly Chinese immigrants. METHODS: The participants were 444 elderly
      immigrants who migrated from Mainland China to Canada. They were a part of a
      random sample of 2272 elderly Chinese living in the communities and took part in
      a face-to-face interview to answer questions in an orally administrated
      questionnaire. The depressive symptoms of the participants were measured by a
      Chinese version of the Geriatric Depression Scale. Data obtained from the 444
      elderly Chinese immigrants was analyzed to assess the impact of various
      psychosocial factors on the number of depressive symptoms that they reported.
      RESULTS: The findings indicated that 23.2% of the elderly immigrants were
      assessed to have some depressive symptoms. When other predicting variables were
      adjusted, elderly immigrants with more chronic illnesses, less positive attitude
      towards ageing, poorer physical health, less adequate financial situation, lower
      level of ethnic identification as Chinese, more service barriers, lower level of
      life satisfaction, shorter length of residency in Canada and those who lived
      alone tended to have more depressive symptoms. CONCLUSIONS: The findings indicate
      that the prevalence rate of depressive symptoms among our elderly immigrant
      sample is higher than the one reported in a general elderly population. While
      further research is recommended to examine the reasons for such a difference,
      culturally appropriate health services, including health promotion programs,
      should be promoted to reduce mental health disparities.

PMID- 15161534
TI  - Proliferative response of human prostate cancer cell to hormone inhibited by
      androgen receptor antisense RNA.
AB  - BACKGROUND: The failure of endocrine treatment for advanced prostate cancer might
      be related to aberrant activation of androgen receptor (AR). Prostate cancer cell
      line LNCaP contains AR that can be activated by androgen, estrogen and
      progesterone. This study was set to investigate the effects of antisense AR RNA
      on growth of LNCaP cultured in medium containing varied concentrations of R1881,
      17beta-estradiol, and progesterone, respectively. METHODS: LNCaP cells
      transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as
      LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP
      and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative
      cells of LNCaP and tranfected LNCaPs were counted by typan staining when they
      cultured with synthetic androgen R1881, 17beta-estradiol, and progesterone,
      respectively. RESULTS: Growth of LNCaPas-AR was inhibited significantly (P <
      0.05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L
      17beta-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen
      between LNCaP and LNCaPNeo (P > 0.05). Microscopic observation showed that LNCaP
      and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive.
      CONCLUSIONS: Our observations indicate that antisense AR RNA retroviral vector pL
      AR-SN could change androgen-independent characteristics of LNCaP cells, which
      might shed some novel insights into the treatment of androgen-independent
      prostate cancer.

PMID- 15161535
TI  - A nomogram for prediction of absorption rate coefficient.
AB  - BACKGROUND: Previous studies have suggested that nomogram can simplize
      complicated calculations of several variables. A simple nomogram was constructed
      to estimate absorption rate coefficient (k(a)) by using the peak time (tpeak) and
      the elimination rate coefficient (k(e)) of drugs administered orally. METHODS:
      The nomogram was based on the plasma concentration-time (C-T) curve equation and
      the function relation between t(peak), k(a) and k(e). A mathematical analysis was
      presented for the construction of single chart nomogram. To check the degree of
      accuracy of the developed nomogram, we used it to analyze retrospective profiles
      of 46 drugs and compared the ka values obtained graphically and those calculated
      by numerically solving the descriptive equation. In addition, we measured the
      carbocisteine concentration of 18 healthy volunteers by HPLC with fluorescence
      detection. To analyze performance error, the measured carbocisteine
      concentrations were compared with predicted concentrations by the ka obtained
      from the nomograms along with the other pharmacokinetic parameters. RESULTS: The
      estimated of k(a) values from nomograms were in very close proximity with the
      numerical values. The performance error was as follows: median performance error
      (MDPE) and median absolute performance error (MDAPE) were 1.32% and 18.15%,
      respectively. CONCLUSIONS: The developed nomogram is accurate and reliable. The
      size of performance error meets the demand of clinical pharmacokinetics.
      Therefore, the nomograms can offer another convenient and easy method for
      rational individualized dosage regimens.

PMID- 15161536
TI  - Validation of real-time three-dimensional echocardiography for quantifying left
      and right ventricular volumes: an experimental study.
AB  - BACKGROUND: Assessment of the left ventricular (LV) and the right ventricular
      (RV) volumes and their functions is important for prognostic prediction and
      clinical decision making. We compared the accuracy for quantifying the LV and the
      RV volumes in vitro between conventional two-dimensional echocardiography (2DE)
      and real-time three-dimensional echocardiography (RT3DE). METHODS: The volumes of
      37 rubber-models (10 regularly shaped to simulate normal LV, 7 shaped to simulate
      LV with symmetric aneurysm, 8 shaped to simulate LV with asymmetric aneurysm, and
      12 irregularly shaped to simulate normal RV) and 10 excised canine hearts were
      measured by RT3DE and 2DE. On RT3DE "full volume" imaging, the inner-surfaces of
      the rubber-models and canine LV and RV were outlined and the volumes were
      measured using 2-, 4-, 8- and 16-plane methods with the RT3DE analysis software.
      On 2DE imaging, the volumes were measured by the Simpson method. The LV and RV
      volumes measured by drained water were served as reference values, with which we
      compared RT3DE and 2DE data. RESULTS: In rubber models mimicking normal LV and LV
      with symmetric aneurysms, RT3DE results were strongly correlated with reference
      values (r = 0.795 - 0.998) and there was a good correlation between 2DE estimates
      and reference values (r = 0.715 - 0.729). There were no significant differences
      between RT3DE estimates, 2DE results and reference values (P > 0.05). In rubber
      models mimicking the RV and LV with asymmetric aneurysm, RT3DE strongly
      correlated with reference values (r = 0.765 - 0.988), but 2DE weakly correlated
      with reference values (r = 0.518 - 0.592). There were no differences between
      RT3DE and reference values (P > 0.05), but a significant difference between 2DE
      and reference values occurred (P < 0.05). For excised canine hearts, there was a
      strong correlation between RT3DE and reference values (r = 0.728 - 0.914), while
      2DE showed a less obvious correlation (r = 0.502 - 0.615). Again, there were no
      significant differences between RT3DE and reference values (P > 0.05), but there
      was a significant difference between 2DE and reference values (P < 0.05).
      CONCLUSIONS: RT3DE can accurately quantify LV and RV volumes and provides a new
      tool to evaluate LV and RV function. For LV and RV measurements by RT3DE, 8-plane
      strategy is the optimum choice for accuracy and convenience.

PMID- 15161537
TI  - Comparison of (99)mTc-methoxyisobutylisonitrile myocardial single-photon emission
      computed tomography and electron beam computed tomography for detecting coronary
      artery disease in patients with no myocardial infarction.
AB  - BACKGROUND: Previous studies have compared single-photon emission computed
      tomography (SPECT) and electron beam computed tomography (EBCT) in detection of
      coronary artery disease (CAD) in patients with myocardial infarction (MI). The
      purpose of this study was to compare SPECT with EBCT in detection of CAD in
      patients with no MI. METHODS: One hundred and forty-seven patients with suspected
      CAD underwent stress-rest (99)mTc-methoxyisobutylisonitrile ((99)mTc-MIBI)
      myocardial SPECT, cardiac EBCT and coronary angiography (CAG) within one month.
      Of them, 73 patients (aged 52.6 +/- 10.6 years old) with no history of MI were
      included in this study. Coronary artery calcium (CAC) was defined as a CT value
      >or= 130 HU within the boundary of coronary artery on EBCT. RESULTS: There were
      35 and 38 patients with or without CAD according to CAG. Ninety-six percent of
      the patients with abnormal SPECT and CAC had a coronary arteries stenosis >or=
      50%, and 90.9% patients with normal SPECT and EBCT showed no CAD. The sensitivity
      of SPECT and EBCT in detection of CAD was comparable, and the specificity of
      SPECT (92.1%) was significantly higher than that of EBCT (55.3%) (P < 0.005). For
      the detection of individual coronary artery stenosis, both sensitivity and
      specificity of SPECT (75.0% and 93.7%) were significantly higher than those of
      EBCT (53.3% and 76.7%) (P < 0.025 and P < 0.005, respectively). In patients
      without chest pain, the sensitivity and specificity of SPECT (76.9% and 91.4%)
      were significantly higher than those of EBCT (23.1% and 69.0%) in detection of a
      coronary artery stenosis of >or= 50% (P < 0.01 and P < 0.005, respectively).
      However, in patients with chest pain, both sensitivity and specificity of SPECT
      were comparable to those of EBCT. In patients <or= 45 years old, the sensitivity
      of SPECT (77.8%) was significantly higher than that of EBCT (27.8%) in assessing
      a coronary artery stenosis of >or= 50% (P < 0.005), and the specificity of SPECT
      was comparable to that of EBCT. In patients > 45 years old, the specificity of
      SPECT (94.3%) was significantly higher than that of EBCT (70.5%) (P < 0.005), and
      the sensitivity of SPECT was comparable to that of EBCT. CONCLUSION: (99)mTc-MIBI
      myocardial perfusion SPECT has higher accuracy than that of EBCT in detection of
      CAD in patients without MI.

PMID- 15161538
TI  - Genetic and environmental risk factors for primary open-angle glaucoma.
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is characterized by optic nerve
      damage and consists of a group of genetically heterogeneous disorders. This study
      was to investigate the associations of genetic and environmental factors with
      POAG in a hospital-based Chinese population. METHODS: Thirty-two adult onset POAG
      patients and 96 age-sex matched control subjects were studied by multivariable
      logistic regression analysis for the relationships between POAG and its risk
      factors including family history, diabetes, hypertension, cardiovascular
      diseases, cigarette smoking, alcohol consumption and polymorphisms of the
      myocilin and the optineurin genes. RESULTS: Univariate analysis showed that POAG
      was related to family history, cardiovascular disease, alcohol consumption and a
      myocilin sequence alteration (T353I) (P < 0.04). Multivariable logistic
      regression analysis confirmed that POAG was significantly associated with family
      history (OR = 20.2), hypertension (OR = 3.58), cigarette smoking (OR = 10.8),
      alcohol consumption (OR = 0.028) and T353I (OR = 6.03, all P < 0.05).
      CONCLUSIONS: Family history, hypertension, cigarette smoking and T353I in the
      myocilin gene are risk factors for POAG. Alcohol consumption, however, has a
      protective effect.

PMID- 15161539
TI  - Interleukin-1 receptor antagonist eye drops promoting high-risk corneal
      allografts survival in rats.
AB  - BACKGROUND: Immune rejection is the main reason of grafts failure after corneal
      transplantation. This study was to determine whether interleukin-1 receptor
      antagonist (IL-1ra) eye drops could prolong corneal allografts survival in high
      risk corneal orthotopic allotransplantation in rat model and to study the effect
      of IL-1ra on the expression of CD1-positive cells in the grafts. METHODS: For all
      experiments, the Sprague-Dawley (SD) rats' corneas were transplanted into Wistar
      rats' eyes. High-risk transplants included those that had been sutured into
      Wistar recipient beds with corneal neovascularization induced by placement of
      three interrupted sutures in the host cornea 7 days earlier. All the animals were
      divided, in a masked fashion, into three treatment groups and one control group.
      Each treatment group received IL-1ra eye drops of different concentrations (1
      mg/ml, 3 mg/ml, or 5 mg/ml, respectively) four times a day for 30 days. The
      control group received 0.9% normal saline (NS) eye drops in the same way as the
      treatment groups. All allografts were evaluated for signs of rejection from the
      first day after surgery. Ten days later, corneal specimens were processed to
      examine the expression of CD1-positive cells and histopathological changes.
      RESULTS: The survival time of the transplants was 5.80 +/- 0.79, 5.89 +/- 1.05,
      6.78 +/- 0.83, and 9.00 +/- 2.36 days respectively in the control or three
      treatment groups. Compared with the control group, 1 mg/ml IL-1ra eye drop did
      not prolong the survival time of the allografts (t = 0.210, P > 0.05). However, 3
      mg/ml and 5 mg/ml IL-1ra eye drop did prolong the survival time of the grafts (t
      >or= 2.627, P < 0.05), with the latter showing more obvious effect.
      Immunohistochemical examinations showed a significant decrease in inflammatory
      cell and CD1-positive cell infiltration in IL-1ra treated groups compared with
      the control group. CONCLUSIONS: IL-1ra can promote corneal allograft survival in
      a dose-dependant manner by reducing the infiltration of CD1-positive cells in
      high-risk corneal transplantation.

PMID- 15161540
TI  - Early activation of caspase-1 after retinal ischemia and reperfusion injury in
      mice.
AB  - BACKGROUND: Caspases are important in the signaling pathway of cellular
      apoptosis. Caspase-3 protein expression has been shown to increase and parallel
      to neuronal apoptosis in retinal ischemia injury. This study was to determine
      whether caspase-1 is involved in neuronal cell death or in retinal ischemia and
      reperfusion injury. METHODS: In twenty-one adult mice, ischemia was induced by
      increasing the intraocular pressure. The animals were sacrificed at 1 hour, 3
      hours, 6 hours, 1 day, 3 days and 7 days after reperfusion. Frozen sections were
      used for caspase-1 immunostaining and TUNEL labeling. RESULTS: In normal retina,
      no caspase-1 positive cells were seen. One hour after ischemia, numerous positive
      cells were noted in the ganglion cell layer (GCL) and inner side of inner nuclear
      layer (INL). At 3 hours, caspase-1 positive cells continued to increase and
      peaked at 6 hours, then decreased significantly at 1 day. TUNEL positive cells
      were detected at 3 hours and peaked at 1 day after ischemia. Double labeling of
      caspase-1 and TUNEL only showed few cells with co-localization after ischemia.
      CONCLUSION: Caspase-1 immunoreactivity preceds to the TUNEL labeling in the GCL
      and INL after retinal ischemia and reperfusion injury and its early activation
      may play an important role in the initiation of neuronal apoptosis.

PMID- 15161541
TI  - Expression of pax-6 in rhesus monkey of optical defocus induced myopia and form
      deprivation myopia.
AB  - BACKGROUND: Pax-6 gene plays an important role in the process of eye development.
      This study was to determine the role of pax-6 in the axial myopia produced by
      hyperopic optical defocus and form deprivation in infant monkeys. METHODS: Among
      seven normal infant rhesus monkeys (aged 1 to 1.5 months), five wore -3.00 D
      spectacle lenses over their right eyes and zero-powered lenses over their left
      eyes. Monocular form deprivation was produced by eyelid fusion in two monkeys.
      Ten weeks later, the monkeys were sacrificed by an overdose of barbiturates and
      their eyes were removed immediately. A 5 mm x 5 mm button of retina and sclera
      was taken from the posterior poles along with a 4-mm optic nerve. RNA was
      isolated separately from each of these three types of tissues. After that,
      reverse transcription polymerase chain reaction (RT-PCR) was used for determining
      gene expression in the retina, sclera and optic nerve. Semi-quantitative analyses
      were performed on the PCR products. RESULTS: As expected, the optically induced
      hyperopic defocus and the form deprivation produced myopic growth. For the lens
      treatment monkeys, pax-6 gene expression in the retinas of the defocused eyes was
      significantly higher than in the retinas of the left eyes (t = 5.703, P = 0.005).
      However, there were no analogous significant differences between pax-6 expression
      in the scleras or the optic nerves. For the two form-deprived monkeys, there were
      no obvious differences in pax-6 gene expression in the retinas or the optic
      nerves. CONCLUSION: The result that the expression of pax-6 was enhanced by
      hyperopic defocus in the infant monkey retina suggests that pax-6 may be involved
      in vision-dependent eye growth and emmetropization.

PMID- 15161542
TI  - Autosomal dominant coralliform cataract related to a missense mutation of the
      gammaD-crystallin gene.
AB  - BACKGROUND: Congenital cataract is a sight-threatening disease that affects about
      1 - 6 cases per 10000 live births and causes 10% - 30% of all blindness in
      children. About 25% of all cases are due to genetic defects. We identified
      autosomal dominant congenital coralliform cataracts-related genetic defect in a
      four-generation Chinese family. METHODS: Complete ophthalmological examinations
      were performed prior to lens extraction. Lens samples were then studied by
      electron microscopy. Genomic DNA from family members were examined using whole
      genomic linkage analysis, with two-point logarithm of odds (LOD) scores
      calculated using the Linkage program package (version 5.1). Mutation analysis of
      candidate genes was performed by direct sequencing. Finally, a three-dimensional
      protein model was predicted using Swiss-Model (version 2.0). RESULTS: Eleven of
      the 23 examined individuals had congenital cataracts. Ultrastructure studies
      revealed crystal deposits in the lens, and granules extensively dispersed in
      transformed lens fiber cells. The maximum two-point LOD score, 3.5 at theta =
      0.1, was obtained for the marker D2S325. Mutation analysis of the gamma
      crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD
      crystallin (CRYGD). Protein structure modeling demonstrated that the P23T
      mutation caused a subtle change on the surface of the gammaD protein.
      CONCLUSIONS: The results suggest that the coralliform cataract phenotype is due
      to a mutated CRYGD gene, and that this sequence change is identical to one
      reported by Santhiya to be related to another distinct clinical condition,
      lamellar cataract. This study provides evidence that this same genetic defect may
      be associated with a different phenotype. This is the first report identifying
      the genetic defect associated with an autosomal dominant congenital coralliform
      cataract.

PMID- 15161543
TI  - Stereo morphology of temporal bone and ear.
AB  - BACKGROUND: The temporal bone has the most complicated anatomic feature among the
      whole human body, which always challenges otolaryngologists. This study was to
      study three-dimensional (3D) morphology of the temporal bone and the ear by means
      of a computer image processing technique, for the purpose of providing a 3D image
      to help in pathological, diagnostic and surgical procedures. METHODS: Forty sets
      of temporal bone celloidin serial sections with reference points were prepared
      and the contours of selected structures and reference points were entered into a
      graphics programme. The technique of computer-aided 3D reconstruction was applied
      to obtain 3D images and parameters of the temporal bones and the ears. Stereo
      views of the ossicles (n = 5), the facial nerves (n = 11), the posterior tympanic
      sinuses (n = 11), the posterior ampullary nerves (n = 4), the endolymphatic ducts
      and sacs (n = 5), and the bony and membranous labyrinth (n = 1) were
      reconstructed. RESULTS: Three-dimensional images, including the cochlea, the
      ossicles, the nerves, the tendons and the endolymphatic fluid system in the
      temporal bone, were obtained. Stereo picture pairs and 3D parameters of spatial
      dimensions, angle and volume for these reconstructed structures were calculated.
      The arrangement of the ossicles, spatial relationship of the bony and membranous
      labyrinth, the whole course of the facial nerves, the endolymphatic sac and
      posterior tympanic cavity were clearly observable. Stereo picture pairs made the
      spatial relationships among the above-mentioned structures much clearer. The
      operation of the posterior ampullary nerve transection was designed and simulated
      on the graphic computer based on 3D anatomic investigations. CONCLUSION: The
      technique of computer-aided 3D reconstruction provides a new tool to observe the
      morphology of the temporal bone and thus may allow design and study of new
      surgical approaches.

PMID- 15161544
TI  - Effects of short-term adaptation to new complete dentures on perception
      thresholds for interocclusal thickness in experienced and non-experienced denture
      wearers.
AB  - BACKGROUND: The ability of patients to discriminate thickness can change with
      time after the insertion of new complete dentures, and this adaptation may differ
      according to the experiences of the patients. If so, an education program to
      reinforce the oral functions may be needed. This study was to evaluate patients'
      ability to discriminate thickness by comparing experienced and non-experienced
      denture wearers after the insertion of new complete dentures. METHODS: Forty
      edentulous patients with a skeletal Class I jaw relationship without any
      temporomandibular disturbances were in the study. After insertion of new complete
      dentures, all patients were tested for discrimination threshold for interocclusal
      thickness. The thickness perception test was repeated on days 1, 7, and 30 after
      the insertion of new dentures. The discriminatory ability was assessed with steel
      and aluminium foils placed between the upper and lower central incisor teeth. The
      records included the duration of wearing dentures. The data were subjected to
      statistical analysis of two-way ANOVA, multiple comparison test and Student's t
      test. RESULTS: Discrimination of tactile ability significantly increased over 30
      days in experienced denture wearers as compared with non-experienced patients (P
      < 0.001). The difference in thickness perception threshold was statistically
      significant between the two groups (P < 0.001). CONCLUSION: Adaptation and
      denture experience can affect thickness discrimination of complete denture
      wearers.

PMID- 15161545
TI  - Klotho is a serum factor related to human aging.
AB  - BACKGROUND: Does klotho (KL) protein exist in human serum, and is there any
      correlation between KL protein in serum with human aging? In order to answer
      those questions, we identified KL protein in human serum and established the
      correlation between KL protein in human serum and aging. METHODS: We prepared a
      polyclonal antibody against human KL protein that was able to recognize the C
      terminal of human secreted KL protein. Western blot and enzyme-linked
      immunosorbent assay (ELISA) were used to identify KL protein in human serum.
      RESULTS: In Western blot, the antibody specifically recognized a 60-kD KL protein
      in both human and mice serum. The population aged from 0 to 91 years screened by
      ELISA revealed that the level of serum KL declined while age increased, though
      each individual level was variable and that the trend of decreasing in serum KL
      had no difference in sex. CONCLUSION: Our data suggest that KL is a serum factor
      related to human aging.

PMID- 15161546
TI  - Clinical and genetic features of International Collaborative Group-hereditary
      nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis
      colorectal cancer families.
AB  - BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most
      common genetic syndrome related with mutation of human mismatch repair genes.
      This study was to evaluate the clinical significance of suspected hereditary
      nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic
      features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC
      families. METHODS: Twenty-nine ICG-HNPCC families fulfilling the Amsterdam
      criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected.
      PCR-SSCP and DNA sequencing analysis were employed to screen the germline
      mutations of the hMLH1 and hMSH2 genes in these families. RESULTS: The ICG group
      had more colorectal cancer (CRC) patients per family than did the suspected group
      (P < 0.05). No statistical difference was observed in Lynch classification and
      familial tumor spectrum. In both groups of families, colorectal cancer was the
      most frequent malignancy, and carcinomas of the stomach, pancreas and uterus were
      the three most common extracolonic malignancies. Mutation screening showed that
      ICG-HNPCC and sHNPCC families had a similar mutation rate (31.0% vs 29.4%, P >
      0.05), mutation type, and mutation distribution. Comparison of the families with
      and without mutation showed no significant difference in CRC patients per family,
      Lynch classification, and tumor spectrum. CONCLUSIONS: ICG-HNPCC and sHNPCC
      families that have similar clinical manifestations and genetic basis indicate a
      similar nature for cancer development. The application of sHNPCC criteria I will
      facilitate clinical diagnosis and treatment of small families.

PMID- 15161547
TI  - Transcriptional repression of hDaxx enhanced by adenovirus 12 E1B 55-kDa
      oncoprotein interacting with hDaxx.
AB  - BACKGROUND: Daxx has been identified as a nuclear protein that involves in
      apoptosis and transcriptional repression. Daxx co-localizes with the
      promyelocytic leukemia (PML) protein and regulates transcription. Human Daxx
      (hDaxx) is a protein that functions as a transcriptional regulation through its
      interaction with some DNA-associated proteins. The aim of this study was to
      explore the transcriptional regulatory effect of hDaxx interacting with
      adenovirus (Ad) 12 E1B (Ad12E1B) 55-kDa oncoprotein. METHODS: The co-localization
      of hDaxx-Ad12E1B or hDaxx-PML protein in the nucleus was observed under a
      confocal microscope. Interaction of hDaxx and Ad12E1B was analyzed by yeast two
      hybrid assay. Direct binding of hDaxx and Ad12E1B was analyzed using
      coimmunoprecipitation and Western blot in vivo and in vitro. The activity of a
      luciferase reporter gene, which was regulated by an hDaxx modulated thymidine
      kinase (TK) promoter, was detected in an automat luminometer. RESULTS: Ad12E1B,
      which co-localized with hDaxx in the nuclei of G401-CC3 cells, disrupted the co
      localization of hDaxx and PML in the PML oncogenic domains (PODs). hDaxx bound
      directly to Ad12E1B in vivo and in vitro. hDaxx interacted with Ad12E1B along its
      full length. Ad12E1B enhanced transcriptional repression activity of hDaxx.
      CONCLUSION: Ad12E1B disrupts the co-localization of hDaxx with PML in PODs and
      enhances transcriptional repression activity of hDaxx.

PMID- 15161548
TI  - Limited posterior left atrial linear radiofrequency ablation for patients with
      chronic atrial fibrillation undergoing rheumatic valvular heart surgery.

PMID- 15161549
TI  - Treatment effect of uvulopalatopharyngoplasty on autonomic nervous activity
      during sleep in patients with obstructive sleep apnea syndrome.

PMID- 15161550
TI  - Multifocal electroretinogram in evaluating retinal function of diabetic macular
      edema after pars plana vitrectomy.

PMID- 15161551
TI  - A surgical approach to middle ear can preserve rat cochlear function.

PMID- 15161552
TI  - A novel Rad gene polymorphism combined with obesity increases risk for type 2
      diabetes mellitus.

PMID- 15161553
TI  - Expression of AT(1a) mRNA in rat hepatic stellate cells and its effects on cell
      growth collagen production.

PMID- 15161554
TI  - Overexpression of amyloid precursor protein inhibits neurite outgrowth and
      disrupts cytoskeleton in N2a cells.

PMID- 15161555
TI  - Polymorphic distribution of Y-chromosome haplotype and mitochondrial DNA in the
      Bouyei people in China.

PMID- 15161556
TI  - Evaluation of MRI in the diagnosis of hepatic tuberculoma.

PMID- 15161557
TI  - Secondary silent sinus syndrome: case report.

PMID- 15161558
TI  - Oligodontia associated with femoral bifurcation, tibial hemimelia and cleft hand.

PMID- 15161559
TI  - Gene deletion analysis of a Chinese boy with Xp21 contiguous gene deletion
      syndrome.

PMID- 15161560
TI  - Eosinophils in asthma.

PMID- 15161561
TI  - Enhancing our hospital with science and technology and taking people as basis.

PMID- 15161562
TI  - PC-Spes rears its head again!

PMID- 15161564
TI  - Patterns of practice in the United States: insights from CaPSURE on prostate
      cancer management.
AB  - The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a
      national disease registry of more than 10,000 patients with prostate cancer
      treated at 31 primarily community-based sites across the country. The database
      tracks oncologic and health-related quality-of-life outcomes. Because the
      urologists participating in the project treat according to their usual practices,
      CaPSURE facilitates the study of trends in disease-management strategies,
      offering a reflection of "real world" practice patterns. This review highlights
      key studies during the past several years that document downward risk migration,
      validates widely used prognostic nomograms, establishes prostate-specific antigen
      doubling time as a surrogate endpoint for disease-specific mortality, assesses
      the impact of treatment on patient-reported quality of life, and presents
      national trends in imaging test use and primary treatment strategies for
      localized disease.

PMID- 15161563
TI  - Genetic alterations in prostate cancer.
AB  - Prostate cancer is the number one malignancy among men. The search for causative
      factors has proven to be difficult and, accordingly, treatment options for
      advanced prostate cancer remain limited. However, technologic breakthroughs in
      the fields of genetics and molecular biology have advanced our understanding of
      the mechanisms involved in prostate carcinogenesis. The aim of this article is to
      review the most recent evidence for the role of various genetic insults at
      specific steps in tumor formation and to suggest potential therapeutic targets.

PMID- 15161565
TI  - Three-dimensional conformal brachytherapy for prostate cancer.
AB  - Because innovations in radiation treatment planning have dramatically improved
      the precision of external beam radiotherapy for prostate cancer with the advent
      of conformal three-dimensional conformal therapy and intensity modulated
      radiotherapy, similar developments are emerging for prostate brachytherapy.
      Computer software programs are facilitating the ability to rapidly create
      conformal treatment plans in the operating room, taking into account the three
      dimensional reconstruction of the prostate target and adhering to dose-volume
      constraints of the normal tissues including the urethra and rectum. Although
      excellent dose distributions can be achieved with pre-planning techniques,
      intraoperative planning takes into account the intraoperative geometry of the
      prostate and the surrounding normal tissues and can consistently produce seed
      implants with reduced urethral and rectal doses while delivering the intended
      prescription dose to the target volume. Current developments are pursuing methods
      to dynamically modify the treatment plan as the implant procedure is ongoing
      based on the coordinates of the deposited seeds. Such approaches will minimize
      the possibility of tumor underdosage and further enhance the conformality of
      prostate brachytherapy.

PMID- 15161568
TI  - High-dose intensity modulated radiation therapy for prostate cancer.
AB  - The trend in prostate cancer radiation over the past several years has been to
      increase the dose to the gland while minimizing the dose to normal tissues.
      Intensity modulated radiation therapy is a computer-driven treatment planning and
      delivery system that has shown promise in improving disease-free outcome while
      decreasing the associated gastrointestinal and urinary complication rates. This
      technique continues to evolve, working toward image-guided radiation therapy,
      which is adjusted daily for positional and architectural changes of the gland.

PMID- 15161566
TI  - Management of patients with an increasing prostate-specific antigen after radical
      prostatectomy.
AB  - Since the late 1980s, early detection and monitoring of men for prostate cancer
      by serum prostate-specific antigen (PSA) measurement has resulted in an increase
      in the number of men presenting with a potentially curable disease. During the
      same time, in an attempt to provide a definitive cure, radical prostatectomy has
      been performed increasingly and now is regarded as the management option of
      choice for many patients with clinically localized prostate cancer. Radical
      prostatectomy involves the removal of all of the prostate tissue resulting in the
      serum PSA level to steadily decline to an undetectable level within 4 to 6 weeks
      after surgery. Despite improvements in surgical technique and a marked downward
      stage shift brought about by serum PSA testing, approximately 25% of men
      ultimately will experience a subsequent increase in serum PSA to a detectable
      level indicating disease recurrence after radical prostatectomy within 15 years.
      In this brief review, the factors associated with a high risk for disease
      recurrence after radical prostatectomy are discussed. Factors indicating whether
      the increasing serum PSA is caused by local recurrence or metastatic disease and
      the management options available to address serum PSA recurrence also are
      discussed.

PMID- 15161567
TI  - Early versus late hormonal therapy for prostate cancer.
AB  - Hormonal therapy remains the critical therapeutic option for men with advanced
      prostate cancer. However, considerable uncertainty remains regarding the
      appropriate choice/timing and actual benefits of hormonal therapy in various
      situations. This article reviews the relevant studies of immediate versus
      deferred hormonal therapy in patients with prostate cancer. The evidence from the
      data supports that early treatment is beneficial to many patients. Significant
      survival benefit of early hormonal therapy has been observed among patients with
      asymptomatic metastatic disease, node-positive but clinically localized disease
      after radical prostatectomy and lymphadenectomy, and advanced local/regional
      disease during and after radiotherapy.

PMID- 15161570
TI  - Sexual health recovery after prostatectomy, external radiation, or brachytherapy
      for early stage prostate cancer.
AB  - Each of the three most common contemporary treatments for localized prostate
      cancer, radical prostatectomy, external beam radiotherapy, and brachytherapy, can
      have adverse effects on sexual health. Sexual health outcome can be improved by
      treatment-specific factors, such as the use of nerve-sparing technique during
      radical prostatectomy, or worsened by the use of androgen deprivation before
      external beam radiotherapy or brachytherapy. Contemporary studies that have used
      validated questionnaires to evaluate multiple components of patient-reported
      sexuality following prostate cancer treatments provide benchmarks of sexual
      outcome expectations that are of interest to patients selecting their prostate
      cancer treatment.

PMID- 15161569
TI  - Molecular diagnosis of prostate cancer.
AB  - The diagnosis, staging, and management of prostate cancer as we know it today is
      greatly dependent on our ability to measure serum prostate-specific antigen (PSA)
      concentration. Nevertheless, because serum PSA concentration, particularly when
      less than 10 ng/mL, reflects the presence of benign prostatic hyperplasia more
      often than cancer, there is a clear need for more specific prostate cancer
      markers. The most promising new markers for prostate cancer are the various
      molecular forms of free PSA. Mass spectrometry also is emerging as a potential
      tool in prostate cancer screening. Because it is unlikely that any one marker
      will have 100% sensitivity and specificity, as new serum markers are tested,
      nomograms that incorporate multiple independently predictive parameters for the
      detection of prostate cancer will become indispensable in our efforts to improve
      prostate cancer screening.

PMID- 15161571
TI  - Screening for prostate cancer: updated experience from the Tyrol study.
AB  - The aim of the Tyrol study was to monitor the impact of screening in a natural
      experiment by comparing prostate cancer mortality in Tyrol, where prostate
      specific antigen (PSA) testing was introduced at no charge, with the rest of
      Austria, where it was not strictly organized and not free of charge. In 1993, PSA
      testing was made freely available to men between the ages of 45 and 75 years in
      the Federal State of Tyrol, Austria. At least 70% of all of the men in this age
      range have been tested at least once during the first 10 years of the study.
      Initially, only total PSA was measured, but free PSA measurement was added in
      1995. Since 2001, complexed PSA also has been measured. Digital rectal
      examination was not part of the screening examination. Significant migration to
      lower clinical and pathological stages has been observed since the introduction
      of this screening program. These findings are consistent with the hypothesis that
      the policy of making PSA testing freely available, and the wide acceptance by men
      in the population, is associated with a reduction in prostate cancer mortality in
      an area in which urology services and radiotherapy are available freely to all
      patients. It is our opinion that most of this decline is likely a result of
      aggressive downstaging and successful treatment and that any contribution from
      detecting and treating early cancers will become apparent in the years to come.

PMID- 15161572
TI  - Extended and saturation needle biopsy for the diagnosis of prostate cancer.
AB  - The diagnosis of prostate cancer hinges on the use of systematic ultrasound
      guided transrectal needle biopsy. The choice of technique is important,
      especially for patients with a history of a negative biopsy. Saturation biopsy
      can be considered for patients at risk of cancer who are willing to accept the
      side effects and who understand that clinically insignificant cancers can be
      detected. For patients with previous negative sextant biopsies, expanding the
      zones sampled and increasing the number of biopsy cores can help detect
      significant cancers while they are still confined. However, as extended biopsy
      becomes more commonly performed for initial diagnosis, there likely will be less
      need for saturation biopsy protocols.

PMID- 15161574
TI  - Translating the results of phase III randomized cancer trials into the language
      of physician obligation to patients.

PMID- 15161575
TI  - Adjuvant therapy for resected non-small-cell lung cancer: recent advances,
      emerging agents, and lingering questions.
AB  - Survival rates for all stages of non-small-cell lung cancer (NSCLC) are dismal.
      Despite complete resection of early-stage NSCLC, many patients have recurrence at
      distant metastatic sites, reinforcing the need for effective systemic adjuvant
      therapy. Chemotherapy, and more recently, targeted therapies, have been evaluated
      in the adjuvant setting. Although initial trials did not suggest improved
      survival, a 1995 meta-analysis favored adjuvant cisplatin-based chemotherapy. The
      recently published International Adjuvant Lung Trial confirms this finding and
      suggests a new standard of care. In this paper we review data on adjuvant
      chemotherapy and limitations of recent clinical trials, including those with
      targeted therapies. We also address the most effective and least toxic regimens
      for adjuvant chemotherapy and the subsets of patients likely to derive the most
      benefit.

PMID- 15161573
TI  - Prostate-specific antigen and related isoforms in the diagnosis and management of
      prostate cancer.
AB  - Despite its unparalleled merits for prostate cancer detection and staging,
      prostate-specific antigen (PSA) is not a marker for prostate cancer only, but
      also is expressed in benign conditions. For early detection, limitations of PSA
      are obvious. Its widespread use has led to an extensive amount of expensive and
      often unnecessary diagnostic procedures associated with significant morbidity.
      Total PSA derivatives may enhance the accuracy of prostate cancer diagnosis. The
      ratio of free-to-total PSA improves specificity while maintaining a high
      sensitivity for prostate cancer detection for men with a total PSA of 2.5 to 10
      ng/mL. Human glandular kallikrein also has the potential to be a valuable tool in
      combination with total and free PSA for early diagnosis of prostate cancer.
      Complex PSA seems to be a reliable tool to improve specificity at high
      sensitivity levels in men with suspected prostate cancer (mainly in PSA levels
      below 4 ng/mL). Newly discovered isoforms of free PSA also may impact early
      detection of prostate cancer with encouraging preliminary results that warrant
      further clinical investigation.

PMID- 15161577
TI  - Treatment options for small cell lung cancer.
AB  - Lung cancer remains the leading cause of cancer-related death in the United
      States. Small cell lung cancer (SCLC) comprises 15% to 25% of all lung cancers.
      The leading cause of lung cancer remains smoking, and rates of smoking continue
      to rise in women, whereas rates in other subgroups have slowed. In this article
      we review recent advances in the treatment of limited-stage as well as extensive
      stage small cell lung cancer. In limited-stage disease, the best survival results
      are observed when patients are treated with twice-daily thoracic radiotherapy
      given concurrently with chemotherapy. Patients who have been successful in
      smoking cessation during therapy for limited-stage disease may have a survival
      benefit over those who are unable to quit smoking during treatment. In extensive
      stage disease, the most significant trial is one comparing irinotecan plus
      cisplatin and etoposide plus cisplatin, showing a survival advantage for the
      irinotecan arm. This trial may change the standard of care for patients with
      extensive-stage disease. A similar ongoing trial in the United States is
      attempting to confirm these results.

PMID- 15161578
TI  - Hot flash trial II.

PMID- 15161576
TI  - Estrogen receptor pathways in lung cancer.
AB  - Lung cancer is the leading cause of death from neoplasia in men and women in the
      United States. Some studies suggest that women are more susceptible than men to
      tobacco-induced carcinogenesis and may show higher risk than men for lung cancer
      development from smoking. More recently, increasing biochemical and genetic data
      have supported this male-female difference in response to tobacco. Estrogens may
      be involved in lung carcinogenesis, and estrogen receptors (ERs), mainly ERb, are
      present and functional in normal lung and tumor cell lines and tissues. Estrogen
      can directly stimulate the transcription of estrogen-responsive genes in the
      nucleus of lung cells, and it can also transactivate growth factor signaling
      pathways, in particular the epidermal growth factor pathway. Lung cancer patients
      currently have few effective therapeutic options. An understanding of these new
      developments in estrogen signaling and cross-talk pathways may pave the way for
      innovative combinatorial approaches for treatment of lung cancer and possibly
      chemoprevention.

PMID- 15161579
TI  - Hot flash trial I.

PMID- 15161580
TI  - Hot flash trial III.

PMID- 15161581
TI  - Prevention and management of osteoporosis in women with breast cancer and men
      with prostate cancer.
AB  - Advances in cancer treatment have resulted in improved life expectancies for
      survivors of breast and prostate cancer. As the number of cancer survivors grows,
      the long-term side effects of treatment play an increasingly prominent role in
      the routine care of these patients. Due to similar management approaches,
      survivors of breast and prostate cancer are at increased risk for osteoporosis.
      This review summarizes the prevention and management of osteoporosis and
      osteopenia resulting from cancer treatment in survivors of breast and prostate
      cancer.

PMID- 15161583
TI  - Pain management, including intrathecal pumps.
AB  - Even when managed according to guidelines, approximately 14% of cancer patients
      have unrelieved pain or unacceptable side effects, and there is good evidence
      that patients still are not receiving optimal therapy. Implantable drug delivery
      systems (IDDS) administer small amounts of drugs directly to the spinal cord and
      reduce systemic narcotic exposure by a factor of 300 to one. In a large
      randomized trial of 202 patients with pain scores of 7.5 or higher, despite 200
      mg or more of morphine or equivalent narcotics, IDDS gave better clinical success
      than comprehensive medical management (84.5% vs 70.8%, P=0.05). Pain scores were
      reduced by 52% versus 39%, drug toxicity scores were reduced by 50% versus 17%,
      and IDDS patients lived longer. Even the most refractory pain patients--those
      failed by a month of comprehensive medical management by experts--when
      subsequently provided with IDDS, had a 27% reduction in pain scores and a 50%
      reduction in drug side effects. Given multiple positive small cohort studies and
      a positive high-power randomized trial, IDDS should be considered as the best
      treatment for this population.

PMID- 15161582
TI  - Management of hot flashes in breast cancer survivors and men with prostate
      cancer.
AB  - Hot flashes are a significant complaint among many breast cancer survivors and
      many men undergoing androgen deprivation therapy for prostate cancer. Several
      therapeutic approaches are available to the suffering man or woman. Many of these
      individuals have tried nonpharmacologic and nonconventional approaches. However,
      most nonpharmacologic treatments have not been compared with placebo or were not
      more effective than placebo in prospective, randomized clinical trials. The most
      effective nonhormonal treatments for hot flashes include agents from the
      selective serotonin or noradrenergic reuptake inhibitor (SSRI/SNRI) family.
      Paroxetine, 10 mg/d, or venlafaxine, 37.5 mg/d, are reasonable initial dosages,
      and if symptoms do not improve within a week or two, the dosage can be doubled.
      Gabapentin appears to provide similar benefits, but direct comparisons have not
      been reported. Because of the strong association between gonadal hormones and
      breast and prostate cancer, the use of hormonal agents to treat hot flashes in
      these patients has been limited. However, such hormonal therapies as
      depomedroxyprogesterone acetate can be prescribed for an informed individual who
      experiences bothersome symptoms despite nonhormonal treatments.

PMID- 15161585
TI  - Classification of clear-cell sarcoma.

PMID- 15161586
TI  - Molecular testing for synovial sarcoma.

PMID- 15161587
TI  - Role of gene expression arrays in sarcomas.
AB  - Microarray technology allows the rapid analysis of expression of thousands of
      genes in a sample. Gene expression profiles are likely characteristic of subtypes
      of sarcomas and may be useful in diagnosis and classification of this
      heterogeneous group of tumors. Gene expression may also be useful prognostically
      with respect to the natural history and response to therapy of these tumors.

PMID- 15161584
TI  - Management of anemia in patients with cancer.
AB  - Anemia is extremely common in patients with cancer. Low hemoglobin levels are
      associated with diminished quality of life and possibly decreased overall
      survival. Successful treatment of anemia has undeniable benefits for patients,
      often yielding dramatic symptomatic improvement that can be very satisfying for
      clinicians to observe. This review focuses on evolving issues in the management
      of anemia in patients suffering from cancer. Topics addressed include new
      evidence-based guidelines concerning the use of epoetin alfa, the evolving role
      of darbepoetin alfa in cancer-associated anemia, the potential for concomitant
      iron supplementation to maximize response to erythropoietic agents, the
      unresolved question of whether erythropoietin use affects survival in cancer
      patients, new concerns about the risk of thromboembolism in cancer patients with
      higher hemoglobin levels who are receiving epoetin, and possible
      immunosuppressive effects of blood product transfusions that may have relevance
      to neoplasia progression.

PMID- 15161588
TI  - The role and limitations of radiofrequency ablation in treatment of bone and soft
      tissue tumors.
AB  - Percutaneous radiofrequency ablation (RFA) has evolved as an alternative therapy
      for treatment of certain patients with liver tumors. This novel image-guided
      intervention is a minimally invasive form of therapy with negligible morbidity.
      RFA has also been used for treatment of selected patients with renal and lung
      malignancies who may not be suitable surgical candidates. With the exception of
      osteoid osteomas, surgical management remains the treatment of choice for primary
      bone and soft tissue tumors. The role of RFA in definitive treatment of sarcomas
      has not been investigated. However, RFA has replaced surgery for treatment of
      osteoid osteomas and can play a role in palliation of painful bone and soft
      tissue tumors.

PMID- 15161590
TI  - [Zoonoses and asthma].

PMID- 15161589
TI  - Management of sarcomas of the head and neck.
AB  - Soft tissue and bone sarcomas in the head and neck are rare tumors. The 1000 to
      1500 yearly cases in the United States are distributed among at least 10 main
      histologies and multiple head and neck subsites. Although this makes structured
      studies difficult to perform and high-level evidence-based treatment algorithms
      difficult to find, basic treatment recommendations can be made from the existing
      literature for most histologies and subsites. This paper discusses the
      epidemiology, natural history, and treatment approaches for several of the most
      common head and neck sarcomas, including the "adult soft tissue sarcomas,"
      osteosarcoma, chondrosarcoma of the larynx, angiosarcoma, rhabdomyosarcoma,
      desmoid tumors, and dermatofibrosarcoma protuberans.

PMID- 15161592
TI  - [The availability in Spanish public hospitals of resources for diagnosing and
      treating sleep apnea-hypopnea syndrome].
AB  - INTRODUCTION AND OBJECTIVE: Sleep apnea-hypopnea syndrome is associated with an
      overall deterioration in the patients health and affects between 1 and 2 million
      people in Spain. The objective of the present study was to evaluate the
      diagnostic and therapeutic resources available in Spain for dealing with this
      problem in terms of both infrastructure and human resources. METHODS: We selected
      461 general hospitals, 457 (99.1%) of which answered a questionnaire in the
      course of a telephone interview. RESULTS: At the time of response, 219 hospitals
      (47.5%) reported performing sleep studies. Conventional polysomnography was
      available in 53% of those hospitals, respiratory polygraphy was used in 42%, and
      oximetry in 5%. In 47% of the hospitals, continuous positive airway pressure was
      titrated empirically in most cases; the number of patients being treated with
      CPAP was 109,752, that is, 269 per 100,000 population in Spain. CONCLUSIONS: The
      level of resources available for diagnosing and treating sleep apnea-hypopnea
      syndrome, although improving, is clearly still inadequate. Currently, only 0.49
      polysomnograph and 0.72 polygraph machines are available per 100,000 population,
      whereas 1 and 3 machines, respectively, are deemed necessary. Only 5% to 10% of
      the affected population has been diagnosed, and in 47% of the hospitals
      interviewed continuous positive airway pressure is not properly titrated. These
      results should be a clarion call to the health authorities to take the
      appropriate steps to address this health problem.

PMID- 15161591
TI  - [Prevalence of malnutrition in outpatients with stable chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To determine the prevalence of malnutrition in outpatients with stable
      chronic obstructive pulmonary disease (COPD) followed at a respiratory clinic.
      MATERIAL AND METHOD: In this prospective study, we assessed the nutritional
      status of consecutive outpatients with stable COPD by investigating various
      anthropometric parameters. Patients were malnourished (low body weight) if their
      body mass index was within the bottom quartile of a reference population. Muscle
      mass was determined from the midarm muscle area and if this mass was at or within
      the bottom quartile, muscle wasting was present. Albumin and transferrin plasma
      concentrations were used as a measure of visceral protein stores. Fat stores were
      assessed from body fat and if this value was at or within the bottom quartile,
      calorific malnutrition was present. All patients underwent arterial blood gas
      sampling at rest and spirometry. RESULTS: A total of 178 patients--one woman
      (0.6%) and 177 men (99.4%)--were enrolled in the study, with a mean (SD) age of
      69 (9) years. We found low body weight in 19.1% of the patients, muscle wasting
      in 47.2%, visceral protein depletion in 17.4%, and fat depletion in 19.1%. Of the
      patients with normal weight, 62.9% showed muscle wasting. The proportion of
      patients with a body mass index or midarm muscle area at or within the bottom
      quartile increased significantly with increased bronchial obstruction (P<.001 and
      P=.015, respectively), though 35.7% of the patients showed muscle wasting even
      when COPD was mild. CONCLUSIONS: Many patients with stable COPD suffer
      malnutrition. Nutritional state is worse with more severe COPD. Depletion
      involves both fat stores and muscle and visceral protein stores, but the greatest
      effect is seen in muscle wasting. A significant number of patients with normal
      weight also suffer muscle wasting. Although changes in body composition were
      common in our patients, low body weight was less prevalent than has been reported
      for populations in countries that are socially and economically similar to Spain.

PMID- 15161593
TI  - [Overall long-term survival in lung cancer analyzed in 610 unselected patients].
AB  - INTRODUCTION AND OBJECTIVES: Many studies of lung cancer survival are carried out
      in patients selected for certain features that usually influence prognosis
      favorably. The objective of this study was to assess the overall survival of
      unselected patients with a diagnosis of lung cancer in our practice. PATIENTS AND
      METHODS: We studied 610 patients for whom survival information was available, a
      population comprising 88% of the 694 with lung cancer diagnosed in our hospital
      from 1991 through 1998. The variables analyzed for their correlation with
      survival were age, sex, histology, tumor-node-metastasis (TNM) stage, treatment,
      and time of diagnosis (with patients grouped by 2-year periods). RESULTS: The
      cases of 596 men and 14 women with a mean age of approximately 67 years were
      studied. Small cell tumors were found in 141, non-small cell tumors in 447, and
      other tissue types in 22. Surgical excision was carried out on 118 (19.3%), and
      treatment was confined to control of symptoms for 6.4% of the patients with small
      cell tumors and 40.5% of those with non-small cell cancer. Symptomatic treatment
      alone was more common for patients older than 70 years (52.5%) and less common
      during the last 2 years of the study period (1997-1998: 19%). Overall 5-year
      survival was 7.9% (2.8% in small cell cancer and 9.4% in non-small cell cancer).
      Survival rates were lower in patients over 70 years of age. Significant
      differences in survival were seen for successive TNM stages, with the exception
      of IIIA and IIIB. The 1997-1998 period saw better survival rates, at 40.8% after
      1 year and 11.2% after 5 years. CONCLUSIONS: The survival rates in lung cancer
      patients in our hospital practice are low because the rate of surgical resections
      is low owing to the high percentage of cases found in advanced stages. Our
      observations are similar to those reported from other European countries.

PMID- 15161594
TI  - [Surgical treatment of recurrent spontaneous pneumothorax: what is the optimal
      timing?].
AB  - OBJECTIVES: To analyze the impact on the outcome of video-assisted thoracoscopic
      surgery (VATS) of delaying surgery in patients with previous episodes of
      pneumothorax. MATERIAL AND METHODS: We studied 57 surgical procedures for
      recurrent primary spontaneous pneumothorax. The cases were grouped according to
      the medical history. One group comprised patients treated surgically at the first
      episode of contralateral pneumothorax or the second episode of ipsilateral
      pneumothorax. The second group comprised patients treated surgically at the third
      or successive episode. We compared the 2 groups as to number of thoracotomies,
      number of conversions from VATS to thoracotomy, presence of adhesions, and length
      of postoperative hospital stay. RESULTS: Of the total number of procedures, 13.9%
      were performed during the third or successive episode. In this group the number
      of pleuropulmonary adhesions and the percentage of thoracotomies (whether
      initially indicated or conversions from VATS) was significantly higher (P<.05).
      However, there was no difference between the 2 groups in length of postoperative
      stay. CONCLUSIONS: VATS is the technique of choice for the surgical treatment of
      recurrent primary spontaneous pneumothorax. Such treatment should be performed at
      the first episode of contralateral pneumothorax or the second episode of
      ipsilateral pneumothorax since delayed surgery gives rise to a higher incidence
      of technical difficulties that entail thoracotomies.

PMID- 15161595
TI  - [Pursed lips breathing].

PMID- 15161596
TI  - [Acute confusional syndrome associated with obstructive sleep apnea aggravated by
      acidosis secondary to oral acetazolamide treatment].
AB  - Acute confusional syndrome, or delirium, is a transitory mental state
      characterized by the fluctuating alteration of awareness and attention levels. We
      present the case of a patient with acute confusional syndrome associated with
      obstructive sleep apnea syndrome (OSAS) aggravated by metabolic acidosis induced
      by oral acetazolamide treatment.A 70-year-old man with no history of neurological
      disease was referred with a clinical picture consistent with acute confusional
      syndrome presenting between midnight and dawn. During the admission examination
      infectious, toxic, and neurologic causes, or those related to metabolic or heart
      disease were ruled out. Arterial blood gases measured during one of the nighttime
      episodes of acute confusional syndrome showed mild hypoxia and hypercapnia with
      mixed acidosis. Signs and symptoms suggestive of OSAS had been developing over
      the months prior to admission, with snoring, sleep apnea, and moderate daytime
      drowsiness. Polysomnography demonstrated severe OSAS with an apnea-hypopnea index
      of 38. Mean arterial oxygen saturation was 83%; time oxygen saturation remained
      below 90% was 44%. The attending physician ordered the withdrawal of oral
      acetazolamide, which was considered the cause of the metabolic component of
      acidosis. Treatment with continuous positive airway pressure was initiated at 9
      cm H2O, after a titration polysomnographic study. The patient continued to
      improve.OSAS, for which very effective treatment is available, should be included
      among diseases that may trigger acute confusional syndrome.

PMID- 15161597
TI  - [Pancoast syndrome and endobronchial tumor infiltration as the first
      manifestation of Hodgkin lymphoma].
AB  - The most common cause of Pancoast syndrome is bronchogenic carcinoma. Other less
      common causes are solid tumor metastases, other chest tumors, infections, and
      hematologic neoplasms. Pancoast syndrome due to lymphoma is very rare, and cases
      described in the literature are essentially associated with non-Hodgkin
      lymphomas. In a review of the literature we found a single case of Pancoast
      syndrome secondary to a Hodgkin lymphoma; however, the syndrome manifested during
      recurrence of disease in that patient. We report a case of nodular sclerosis
      Hodgkin lymphoma which first manifested clinically as Pancoast syndrome and which
      was initially diagnosed by bronchial biopsy.

PMID- 15161598
TI  - [Bronchiolitis obliterans organizing pneumonia induced by chemotherapy].

PMID- 15161599
TI  - [Was another consensus document on treating exacerbations of chronic obstructive
      pulmonary disease needed?].

PMID- 15161602
TI  - Angiotensin II directly stimulates activity and alters the phosphorylation of Na
      K-ATPase in rat proximal tubule with a rapid time course.
AB  - We present evidence that Na-K-ATPase in the rat proximal tubule is directly
      activated by ANG II much faster than previously observed. Specifically, we show
      that a 2-min exposure to 0.1 and 1 nM ANG II slowed the rate of intracellular
      sodium accumulation in response to an increase in extracellular sodium added in
      the presence of gramicidin D. From these data, we show that ANG II directly
      stimulates Na-K-ATPase activity at rate-limiting concentrations of intracellular
      sodium. Under these same conditions, exposing proximal tubules to ANG II altered
      the amount of 32P incorporated into multiple phosphopeptides generated from a
      tryptic digest of the alpha-subunit of Na-K-ATPase. Na-K-ATPase was isolated from
      whole cell lysates by means of a ouabain-affinity column and then separated into
      its individual subunits by SDS-PAGE. Na-K-ATPase bound to the column in its E2
      conformation and was eluted by altering its conformation to E1 using Na+ATP. Na-K
      ATPase isolated from cells treated with ANG II eluted more easily from the
      ouabain-affinity column than Na-K-ATPase isolated from control cells, suggesting
      that ANG II decreased the affinity of Na-K-ATPase for ouabain. Thus ANG II
      rapidly stimulated the activity of Na-K-ATPase in 2 min or less by a mechanism
      that could involve changes in phosphorylation and conformation of Na-K-ATPase. We
      suggest that the physiological role for rapid direct activation of Na-K-ATPase is
      greater control of intracellular sodium during sodium reabsorption.

PMID- 15161601
TI  - Reduced IP receptors in STZ-induced diabetic rat kidneys and high-glucose-treated
      mesangial cells.
AB  - Mesangial cells (MG) are an important source of renal PGE2 and PGI2. The purpose
      of this study was to examine the effects of cicaprost (CCP; PGI2 analog) on MG
      function and the expression of IP receptors in streptozotocin (STZ)-diabetic rats
      and glucose-treated MG cells. CCP increased cellular cAMP in immortalized rat MG
      cells. Both glucose and anisomycin attenuated CCP-cAMP, but not PMA, angiotensin
      II, or transforming growth factor-beta. Also, IP receptor protein was reduced in
      response to glucose. While CCP decreased the levels of the cell cycle inhibitor
      p27, it did not alter thymidine or leucine incorporation. However, CCP reduced
      fibronectin levels by 40% and increased matrix metalloproteinase-2 levels
      threefold, a key enzyme in matrix degradation. Finally, IP receptors were
      significantly reduced in the outer medulla of 4- and 12-wk STZ-diabetic rats and
      in the cortex, outer, and inner medullary regions in 6-mo uninephrectomized STZ
      diabetic rats. The changes in the CCP/IP system observed in this study suggest
      that IP may serve as an alternate therapeutic target in diabetes.

PMID- 15161603
TI  - Partial bladder outlet obstruction abolishes the receptor- and G protein
      dependent increase in calcium sensitivity in rabbit bladder smooth muscle.
AB  - Partial bladder outlet obstruction (PBOO) alters the function of the whole
      bladder and produces specific alterations in the contractility of the bladder
      smooth muscle cell. The goal of this study was to test the hypothesis that PBOO
      affects smooth muscle contraction at the level of the receptor- and G protein
      dependent increase in myofilament Ca2+ sensitivity. To address this question, we
      used alpha-toxin-permeabilized strips of bladder smooth muscle from control
      animals and animals subjected to 2 wk of PBOO. Increasing free [Ca2+] increased
      force in permeabilized strips from control animals; the addition of 10 microM
      carbachol and 10 microM GTP increased both the Ca2+ sensitivity of the
      contractions and the maximal levels of force attained. In contrast, although
      increases in [Ca2+] increased force in permeabilized strips from PBOO animals,
      the addition of carbachol and GTP had no additional effects. Myosin light chain
      phosphorylation levels increased with [Ca2+], and although they tended to be
      higher in strips from PBOO animals, they did not reach statistical significance.
      Assessment of G protein activity from both animal models suggests this is not a
      site responsible for the loss of carbachol and GTP enhancement of myofilament
      Ca2+ sensitivity. The addition of phorbol dibutyrate increased the Ca2+
      sensitivity of force development in strips from both animal models, suggesting
      that an alteration in PKC signaling is not involved. Our results are consistent
      with the hypothesis that PBOO decreases receptor-mediated myofilament calcium
      sensitization and that the site of action is downstream from either the G
      proteins or PKC.

PMID- 15161604
TI  - Inhibition of ENaC by intracellular Cl- in an MDCK clone with high ENaC
      expression.
AB  - We examined the effects of intracellular Cl- concentration ([Cl-]i) on the
      epithelial Na channel (ENaC) in a line of Madin-Darby canine kidney (MDCK) cells
      (FL-MDCK) with a high rate of Na+ transport produced by stable retroviral
      transfection with rENaC subunits (Morris RG and Schafer JA. J Gen Physiol 120: 71
      85, 2002). Treatment with cAMP (100 microM 8-cpt-cAMP plus 100 microM IBMX)
      stimulated ENaC-mediated Na+ absorption as well as Cl- secretion via cystic
      fibrosis transmembrane conductance regulator, which was characterized in alpha
      toxin-permeabilized monolayers to have the anion selectivity sequence NO3- > Br-
      > Cl- > I-. With the use of FL-MDCK monolayers in which the basolateral membrane
      was permeabilized by nystatin, the ENaC conductance of the apical membrane
      [determined from the amiloride-sensitive short-circuit current (AS-Isc) driven by
      an apical-to-basolateral Na+ concentration gradient] was progressively inhibited
      by increasing the [Cl-] in the basolateral solution (and hence in the cytosol),
      but it was insensitive to the [Cl-] in the apical solution. This inhibitory
      effect of [Cl-]i occurred regardless of the presence or absence of net Cl-
      transport. However, from fluorometric measurements using the Cl(-)-sensitive dye
      6-methoxy-N-(3-sulfopropyl)-quinolinium in intact FL-MDCK monolayers on permeable
      supports, cAMP, which activates both Na+ absorption and Cl- secretion, produced a
      decrease of [Cl-]i from 76 +/- 14 to 36 +/- 8 mM (P = 0.03). Thus it might be
      expected that activation of Cl- secretion by cAMP would lead to stimulation
      rather than inhibition of ENaC. In the nystatin-treated monolayers, an increase
      in [Cl-]i from 15 to 145 mM decreased AS-Isc from 24.5 +/- 1.0 to 10.2 +/- 1.6
      microA/cm2. This inhibition of ENaC could be attributed to nearly proportional
      decreases in the density of ENaC in the apical membrane from 1.91 +/- 0.16 to
      1.32 +/- 0.17 fmol/cm2 and in the intrinsic channel activity (the average current
      per ENaC subunit) from 13.3 +/- 1.2 to 8.2 +/- 1.4 microA/fmol.

PMID- 15161605
TI  - Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb
      cells.
AB  - Genetic studies indicated that mutations of the chloride channel CLC-5 in the
      kidney are responsible for a group of clinical disorders, collectively called
      Dent's disease. In the kidney, CLC-5 was found to be expressed in the proximal
      tubule, medullary thick ascending limb (mTAL) of loop of Henle, and intercalated
      cells of the collecting tubule. In proximal tubular cells, CLC-5 was found to
      play an important role in receptor-mediated endocytosis. However, the functional
      roles of CLC-5 in mTAL and collecting tubules remain unclear. Because mTAL is
      normally exposed to a hypertonic environment, we aimed to examine the effect of
      hypertonicity on CLC-5 expression in this nephron segment. Our studies revealed
      that exposure to hypertonicity (up to 550 mosM) increased CLC-5 mRNA and protein
      levels in a murine mTAL cell line (MTAL) but not in an opossum kidney (OK)
      proximal tubular cell line. A similar effect was also found in mouse kidneys,
      where CLC-5 expression was enhanced in renal medulla, but not cortex, after 48 h
      of water deprivation. We also tested the effect of hypertonicity on endocytotic
      activity and found that exposure to hypertonicity caused a significant decrease
      in cellular uptake of FITC-labeled albumin in OK but not in MTAL cells. Our
      results suggest that CLC-5 expression is upregulated by hypertonicity in mTAL
      cells but not in proximal tubular cells. We speculate that the increased CLC-5
      levels in mTAL may serve to maintain the endocytotic activity in a hypertonic
      environment.

PMID- 15161607
TI  - How do we catch colds?

PMID- 15161606
TI  - Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3
      kinase signaling in muscle cells: consequences on proteolysis.
AB  - Chronic acidosis is a stimulus for proteolysis in muscle in vivo, but the
      mechanism of this response is unknown. We tested the hypothesis that acidosis or
      TNF-alpha, a cytokine whose production increases in acidosis, regulates
      proteolysis by inhibiting insulin signaling through phosphoinositide 3-kinase
      (PI3K). In cultured L6 myotubes, acidified (pH 7.1) media did not accelerate the
      basal protein degradation rate, but it inhibited insulin's ability to suppress
      proteolysis. Insulin receptor substrate-1 (IRS-1)-associated PI3K activity was
      not altered in cells acidified for 10 min but was strongly inhibited in cells
      incubated at pH 7.1 for 24 h. Phosphorylation of Akt was also suppressed by
      acidification for 24 h. Acidification did not induce changes in IRS-1 abundance,
      insulin-stimulated IRS-1 tyrosine phosphorylation, or the amount of PI3K p85
      regulatory subunit. In contrast to acidification, TNF-alpha suppressed
      proteolysis in the presence or absence of insulin but had no effect on IRS-1
      associated PI3K activity. To establish that the PI3K pathway can regulate protein
      degradation in muscle, we measured proteolysis in cells after inhibition of PI3K
      activity with LY-294002 or infection with an adenovirus encoding a dominant
      negative PI3K p85alpha-subunit. Both approaches inhibited insulin-induced
      suppression of proteolysis to a degree similar to that seen with acidification.
      We conclude that acidosis accelerates protein degradation by impairing insulin
      signaling through PI3K in muscle cells.

PMID- 15161608
TI  - Rifapentine for the treatment of tuberculosis: is it all it can be?

PMID- 15161609
TI  - Transmission of severe acute respiratory syndrome in critical care: do we need a
      change?

PMID- 15161610
TI  - Neovascularization in idiopathic pulmonary fibrosis: too much or too little?

PMID- 15161611
TI  - A century of tuberculosis.

PMID- 15161612
TI  - Corticosteroid resistance in smokers with asthma.

PMID- 15161613
TI  - Psychosocial factors and asthma.

PMID- 15161614
TI  - Fungi and respiratory illness in children.

PMID- 15161615
TI  - Montelukast in respiratory syncytial virus postbronchiolitis.

PMID- 15161616
TI  - Sildenafil in pulmonary arterial hypertension.

PMID- 15161617
TI  - Acute effects of air pollution on admissions: reanalysis of APHEA 2.

PMID- 15161618
TI  - Aerosolized urokinase in pulmonary fibrosis.

PMID- 15161619
TI  - Control, upper airway, and sleep apnea.

PMID- 15161620
TI  - Familial spontaneous pneumothorax and FBN1 mutations.

PMID- 15161621
TI  - Interpretation of breath sounds.

PMID- 15161623
TI  - Physiological and pathological responses to hypoxia.
AB  - As the average age in many countries steadily rises, heart infarction, stroke,
      and cancer become the most common causes of death in the 21st century. The causes
      of these disorders are many and varied and include genetic predisposition and
      environmental influences, but they all share a common feature in that limitation
      of oxygen availability participates in the development of these pathological
      conditions. However, cells and organisms are able to trigger an adaptive response
      to hypoxic conditions that is aimed to help them to cope with these threatening
      conditions. This review provides a description of several systems able to sense
      oxygen concentration and of the responses they initiate both in the acute and
      also in long-term hypoxia adaptation. The role of hypoxia in three pathological
      conditions, myocardial and cerebral ischemia as well as tumorigenesis, is briefly
      discussed.

PMID- 15161624
TI  - Flipping the epigenetic switch.

PMID- 15161626
TI  - Experimental human metapneumovirus infection of cynomolgus macaques (Macaca
      fascicularis) results in virus replication in ciliated epithelial cells and
      pneumocytes with associated lesions throughout the respiratory tract.
AB  - A substantial proportion of hitherto unexplained respiratory tract illnesses is
      associated with human metapneumovirus (hMPV) infection. This virus also was found
      in patients with severe acute respiratory syndrome (SARS). To determine the
      dynamics and associated lesions of hMPV infection, six cynomolgus macaques
      (Macaca fascicularis) were inoculated with hMPV and examined by pathological and
      virological assays. They were euthanized at 5 (n = 2) or 9 (n = 2) days post
      infection (dpi), or monitored until 14 dpi (n = 2). Viral excretion peaked at 4
      dpi and decreased to zero by 10 dpi. Viral replication was restricted to the
      respiratory tract and associated with minimal to mild, multi-focal erosive and
      inflammatory changes in conducting airways, and increased numbers of macrophages
      in alveoli. Viral expression was seen mainly at the apical surface of ciliated
      epithelial cells throughout the respiratory tract, and less frequently in type 1
      pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions
      were distinct from those of SARS-associated coronavirus infection, excluding hMPV
      as the primary cause of SARS. This study demonstrates that hMPV is a respiratory
      pathogen and indicates that viral replication is short-lived, polarized to the
      apical surface, and occurs primarily in ciliated respiratory epithelial cells.

PMID- 15161625
TI  - Adenosine A(2A) receptor activation promotes wound neovascularization by
      stimulating angiogenesis and vasculogenesis.
AB  - Recent reports indicate that circulating endothelial progenitor cells (EPCs) may
      be recruited to sites of neovascularization where they differentiate into
      endothelial cells (EC). As we have previously demonstrated that adenosine A(2A)
      agonists promote neovascularization in wounds, we sought to determine whether
      adenosine A(2A) receptor agonist-augmented wound healing involves vessel
      sprouting (angiogenesis) or EPC recruitment (vasculogenesis) or both. Four weeks
      after bone marrow reconstitution from donor FVB/N Tie2GFP transgenic mice, two
      full-thickness excisional wounds were performed on the dorsum of FVB/N wild-type
      mice and treated with either an A(2A) receptor agonist (CGS-21680) or vehicle
      alone. Vessel density, as measured by CD31 staining, and density of EPC-derived
      vessels, as measured by GFP expression, were quantified in a blinded fashion
      using two-color fluorescence microscopy. We observed nearly a threefold increase
      in CD31-positive vessels and a more than 10-fold increase in GFP-positive cells
      in A(2A) agonist-treated 3-day old wounds, but by 6 days after wounding the
      differences between A(2A) agonist-treated and vehicle-treated wounds were no
      longer statistically significant. In conclusion, this is the first evidence that
      an exogenous agent such as an adenosine A(2A) receptor agonist increases
      neovascularization in the early stages of wound repair by increasing both EPC
      recruitment (vasculogenesis) and local vessel sprouting (angiogenesis).

PMID- 15161627
TI  - Monitoring caspase activity in living cells using fluorescent proteins and flow
      cytometry.
AB  - A molecular probe was developed to monitor caspase activity in living cells by
      flow cytometry. It consists of CFP and YFP with a peptide linker containing two
      caspase-cleavage sites (LEVD). Its expression resulted in intense fluorescence
      resonance energy transfer (FRET), whereas cleavage of this linker by caspases
      eliminated FRET because of physical separation of the CFP and YFP moieties. Using
      flow cytometry, cells expressing this probe exhibited two patterns, strong FRET
      and diminished or absent FRET. The appearance of diminished FRET was inhibited by
      a pan-caspase inhibitor z-VAD or D->A mutations in the LEVD sequence and was
      markedly increased by apoptosis-inducing agents, etoposide and camptothecin, or
      overexpression of a caspase 8-red fluorescent protein fusion protein.
      Importantly, this probe's ability to monitor caspase activity was comparable with
      results obtained with fluorogenic substrates or fluorochrome-labeled inhibitors
      of caspases. Specific caspase inhibitors indicated the probe was highly sensitive
      to cleavage by caspase 6 and 8, less sensitive to caspase 4, and resistant to
      other caspases. Activation of caspase 8 by Fas engagement markedly increased the
      probe's cleavage, whereas treatment of caspase 8-deficient cells with anti-Fas
      did not increase cleavage. However, staurosporine induced cleavage of the probe
      in caspase 8-deficient cells by a mechanism that was inhibited by overexpression
      of bcl-x. Taken together, the data indicate that this caspase-sensitive probe can
      be used to monitor the basal and apoptosis-related activities of caspases,
      including an initiator caspase, caspase 8, and effector caspases, such as caspase
      6.

PMID- 15161629
TI  - Inhibition of proprotein convertases enhances cell migration and metastases
      development of human colon carcinoma cells in a rat model.
AB  - Although proprotein convertases are involved in tumor development, nothing is
      known about their role in metastatic dissemination. To investigate the
      involvement of convertase inhibition, we used human colon carcinoma cells
      overexpressing alpha1-antitrypsin Portland (alpha1-PDX, PDX39P cells), a potent
      convertase inhibitor. We previously reported that these cells bear uncleaved
      integrin alpha subunits and display an altered attachment to vitronectin that is
      correlated with defects in the intracellular signaling pathways activated by
      alphavbeta5 integrin ligation. In this study, we demonstrate that the inhibition
      of proprotein convertase activity either by overexpression of alpha1-PDX or with
      the synthetic inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR
      cmk) led to a significant increase in cell migration supported by the alphavbeta5
      integrin. A collagen gel invasion assay showed that PDX39P cells also displayed
      an invasive ability, contrary to control cells. Moreover, when injected to
      immunosuppressed newborn rats, PDX39P cells were highly invasive, as they induce
      10 times more metastases than mock-transfected cells. In addition, the
      aggressiveness of PDX39P cells can be greatly reduced by a function-blocking
      monoclonal antibody (mAb) against the alphav subunit. It thus seems that
      inhibition of proprotein convertases enhances the in vivo invasiveness of colon
      tumor cells likely due to an increase in cell migration mediated by alphav
      integrins.

PMID- 15161628
TI  - Estrogen receptor-1 (Esr1) and -2 (Esr2) regulate the severity of clinical
      experimental allergic encephalomyelitis in male mice.
AB  - Estrogens and estrogen-receptor signaling function in establishing and regulating
      the female immune system and it is becoming increasingly evident that they may
      play a similar role in males. We report that B10.PL/SnJ male mice with a
      disrupted estrogen receptor-1 (alpha) gene (Esr1(-/-)) develop less severe
      clinical experimental allergic encephalomyelitis (EAE) compared to either Esr1(+/
      ) or wild-type (Esr1(+/+)) controls when immunized with myelin basic protein
      peptide Ac1-11 (MBP(Ac1-11)). In contrast, the disease course in B10.PL/SnJ male
      mice with a disrupted estrogen receptor-2 (beta) gene (Esr2(-/-)) does not differ
      from that of wild-type (Esr2(+/+)) mice. However, Esr2(+/-) mice do develop more
      severe clinical disease with an earlier onset indicating that heterosis at Esr2
      plays a significant role in regulating EAE in males. No significant differences
      in central nervous system histopathology or MBP(Ac1-11)-specific T-cell responses
      as assessed by proliferation and interleukin-2 production were observed as a
      function of either Esr1 or Esr2 genotype. An analysis of cytokine/chemokine
      secretion by MBP(Ac1-11)-specific T cells revealed unique Esr1 and Esr2 genotype
      dependent regulation. Interferon-gamma secretion was found to be negatively
      regulated by Esr1 whereas interleukin-6 and tumor necrosis factor-alpha secretion
      exhibited classical Esr2 gene dose responses. Interestingly, MCP-1 displayed
      distinctively unique patterns of genotype-dependent regulation by Esr1 and Esr2.
      The contribution of the hematopoietic and nonhematopoietic cellular compartments
      associated with the heterotic effect at Esr2 in regulating the severity of
      clinical EAE was identified using reciprocal hematopoietic radiation bone marrow
      chimeras generated between male wild-type and Esr2(+/-) mice. Wild-type -->
      Esr2(+/-) mice exhibited EAE equivalent in severity to that seen in Esr2(+/-) -->
      Esr2(+/-) control constructs; both of which were more severe than the clinical
      signs observed in Esr2(+/-) --> wild-type and wild-type --> wild-type mice. These
      results indicate that the heterotic effect at Esr2 is a function of the
      nonhematopoietic compartment.

PMID- 15161630
TI  - Topical vascular endothelial growth factor accelerates diabetic wound healing
      through increased angiogenesis and by mobilizing and recruiting bone marrow
      derived cells.
AB  - Diminished production of vascular endothelial growth factor (VEGF) and decreased
      angiogenesis are thought to contribute to impaired tissue repair in diabetic
      patients. We examined whether recombinant human VEGF(165) protein would reverse
      the impaired wound healing phenotype in genetically diabetic mice. Paired full
      thickness skin wounds on the dorsum of db/db mice received 20 microg of VEGF
      every other day for five doses to one wound and vehicle (phosphate-buffered
      saline) to the other. We demonstrate significantly accelerated repair in VEGF
      treated wounds with an average time to resurfacing of 12 days versus 25 days in
      untreated mice. VEGF-treated wounds were characterized by an early leaky,
      malformed vasculature followed by abundant granulation tissue deposition. The
      VEGF-treated wounds demonstrated increased epithelialization, increased matrix
      deposition, and enhanced cellular proliferation, as assessed by uptake of 5
      bromodeoxyuridine. Analysis of gene expression by real-time reverse transcriptase
      polymerase chain reaction demonstrates a significant up-regulation of platelet
      derived growth factor-B and fibroblast growth factor-2 in VEGF-treated wounds,
      which corresponds with the increased granulation tissue in these wounds. These
      experiments also demonstrated an increase in the rate of repair of the
      contralateral phosphate-buffered saline-treated wound when compared to wounds in
      diabetic mice never exposed to VEGF (18 days versus 25 days), suggesting that
      topical VEGF had a systemic effect. We observed increased numbers of circulating
      VEGFR2(+)/CD11b(-) cells in the VEGF-treated mice by fluorescence-activated cell
      sorting analysis, which likely represent an endothelial precursor population. In
      diabetic mice with bone marrow replaced by that of tie2/lacZ mice we demonstrate
      that the local recruitment of bone marrow-derived endothelial lineage lacZ+ cells
      was augmented by topical VEGF. We conclude that topical VEGF is able to improve
      wound healing by locally up-regulating growth factors important for tissue repair
      and by systemically mobilizing bone marrow-derived cells, including a population
      that contributes to blood vessel formation, and recruiting these cells to the
      local wound environment where they are able to accelerate repair. Thus, VEGF
      therapy may be useful in the treatment of diabetic complications characterized by
      impaired neovascularization.

PMID- 15161631
TI  - Differential response of human lung epithelial cells to fas-induced apoptosis.
AB  - The Fas (CD95)/Fas ligand (CD178) system plays an important role in epithelial
      damage during the acute respiratory distress syndrome. The goal of this study was
      to determine whether proximal and distal human lung epithelial cells differ in
      their sensitivity to Fas ligand (rh-sFasL), and whether the response of lung
      epithelium to Fas ligation is modulated by proinflammatory cytokines. Although
      the expression of both Fas message and protein was similar in proximal and distal
      lung epithelial cells, only distal cells became apoptotic when exposed to serial
      dilutions of rh-sFasL. Stimulation with tumor necrosis factor-alpha, interleukin
      1beta, or interferon-gamma significantly increased the sensitivity of proximal
      cells to rh-sFasL, and exposure to either tumor necrosis factor-alpha or
      interferon-gamma enhanced the sensitivity of distal cells to Fas ligation. These
      findings suggest that in normal human lungs, the responses of the epithelium to
      Fas ligation become more pronounced from proximal to distal locations.
      Furthermore, proinflammatory cytokines sensitize lung epithelium to Fas-induced
      death. These findings are relevant for understanding the role of the Fas/FasL
      system in acute lung injury, in which epithelial damage occurs primarily in
      distal airway and alveolar epithelium, whereas sFasL is present throughout the
      airspaces.

PMID- 15161632
TI  - Preservation of intestinal structural integrity by zinc is independent of
      metallothionein in alcohol-intoxicated mice.
AB  - Intestinal-derived endotoxins are importantly involved in alcohol-induced liver
      injury. Disruption of intestinal barrier function and endotoxemia are common
      features associated with liver inflammation and injury due to acute ethanol
      exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This
      study was designed to determine the inhibitory effect of zinc on alcohol-induced
      endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is
      independent of MT. MT knockout (MT-KO) mice were administered three oral doses of
      zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being
      administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol
      administration caused liver injury as determined by increased serum
      transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of
      tumor necrosis factor (TNF-alpha). Increased plasma endotoxin levels were
      detected in ethanol-treated animals whose small intestinal structural integrity
      was compromised as determined by microscopic examination. Zinc supplementation
      significantly inhibited acute ethanol-induced liver injury and suppressed hepatic
      TNF-alpha production in association with decreased circulating endotoxin levels
      and a significant protection of small intestine structure. As expected, MT levels
      remained undetectable in the MT-KO mice under the zinc treatment. These results
      thus demonstrate that zinc preservation of intestinal structural integrity is
      associated with suppression of endotoxemia and liver injury induced by acute
      exposure to ethanol and the zinc protection is independent of MT.

PMID- 15161633
TI  - Leukocyte-derived interleukin-1beta interacts with renal interleukin-1 receptor I
      to promote renal tumor necrosis factor and glomerular injury in murine crescentic
      glomerulonephritis.
AB  - The involvement of proinflammatory cytokines interleukin (IL)-1 and tumor
      necrosis factor (TNF) in crescentic glomerulonephritis (GN) is well established.
      Recently the requirement of intrinsic renal cell participation via their
      production of TNF in crescentic GN was demonstrated. The current studies address
      the relative contributions of leukocyte and intrinsic renal cell-derived IL-1beta
      in the induction of TNF production and glomerular injury by studying bone marrow
      chimeric mice. Leukocyte-derived IL-1beta was critical in the development of
      crescentic renal injury because IL-1beta(-/-)-->WT (absent leukocyte IL-1beta)
      chimeric mice had significantly attenuated TNF expression and were protected from
      the development of crescentic GN. In contrast, WT-->IL-1beta(-/-) chimeric mice
      (intact leukocyte but absent renal IL-1beta) developed similar TNF expression and
      crescentic GN to wild-type mice. To determine the cellular target for IL-1 in
      this model, IL-RI chimeric mice were studied. IL-1RI(-/-)-->WT chimeric (absent
      leukocyte IL-1RI expression) mice showed no attenuation of crescentic GN, whereas
      in the absence of renal IL-1RI (WT-->IL-1RI(-/-) chimeras), glomerular TNF
      expression and the development of crescentic GN were significantly decreased.
      These studies demonstrate that leukocytes are the major cellular source of IL
      1beta, and that IL-1beta acts principally via the IL-1RI on intrinsic renal cells
      to induce TNF expression and crescentic glomerular injury.

PMID- 15161634
TI  - Hyaluronan attenuates transforming growth factor-beta1-mediated signaling in
      renal proximal tubular epithelial cells.
AB  - Increased expression of hyaluronan (HA) has been associated with both acute renal
      injury and progressive renal disease, although the functional significance of
      this remains unclear. There is overwhelming evidence that transforming growth
      factor (TGF)-beta1 is critical to the development of progressive renal disease.
      Recent studies suggest an interaction between HA and TGF-beta signaling in cancer
      cell biology. The aim of this study was to examine the potential role of HA as a
      modulator of TGF-beta1 function in renal proximal tubular epithelial cells (PTC).
      Under resting conditions, co-localization of the principal receptor for HA, CD44,
      and both the TGF-beta type I and type II receptors was demonstrated by
      immunoprecipitation and western analysis and further confirmed by
      immunocytochemistry and confocal microscopy. Stimulation of PTC with TGF-beta1
      led to increased synthesis of both type III and type IV collagen assessed by
      Western analysis. Addition of HA did not alter collagen synthesis, but abrogated
      TGF-beta1-mediated increase in type III and type IV collagen. This effect was
      blocked by the addition of a blocking antibody to CD44 and also by inhibition of
      MAP kinase kinase (MEK) activity. Furthermore HA decreased TGF-beta1 activation
      of a luciferase-SMAD responsive construct, and decreased translocation of SMAD4
      into the cell nucleus. We have previously demonstrated an anti-migratory effect
      of TGF-beta1 in a scratch wounding model. As with HA antagonism of TGF-beta1
      extracellular matrix generation, HA reduced the anti-migratory effect of TGF
      beta1 in a CD44-dependent manner. In contrast to the effect of TGF-beta1 on
      collagen synthesis, which is SMAD-dependent, the anti-migratory effect of TGF
      beta1 in this model is known to be dependent of activation of RhoA. In the
      presence of HA, TGF-beta1-mediated activation of RhoA was also abrogated in a
      CD44-dependent manner. The results suggest that co-localization of CD44 and TGF
      beta receptors facilitate modulation of both SMAD and non-SMAD-dependent TGF
      beta1-mediated events by HA. Our results therefore suggest that alteration of HA
      synthesis may represent an endogenous mechanism to limit renal injury.

PMID- 15161636
TI  - Dynamic regulation of estrogen receptor-beta expression by DNA methylation during
      prostate cancer development and metastasis.
AB  - Estrogen receptor (ER)-beta is thought to exert anti-proliferative effects in the
      normal prostate but supports prostate cancer (PCa) cell survival. We previously
      reported that the receptor's expression declined as PCa developed in the gland
      but reappeared in lymph node and bone metastases. To investigate whether
      hypermethylation was the underlying mechanism for these phenomena, we first
      identified two CpG islands (CGIs) encompassing 41 CpG dinucleotides, located
      separately in the untranslated exon 0N and the promoter region of ER-beta. Using
      immunostained, laser capture-microdissected samples from 56 clinical specimens,
      we demonstrated an inverse relationship exists between the extent of ER-beta CGI
      methylation and receptor expression in normal, hyperplastic, premalignant, and
      malignant foci of the prostate and in lymph node and bone metastases. Treatment
      of PCa cell lines (LNCaP and DU145), that express little ER-beta mRNA, with a
      demethylating agent increased levels of receptor expression thus corroborating
      our in vivo findings that methylation is involved in ER-beta silencing.
      Methylation centers in the promoter region and exon 0N were identified by
      hierarchical cluster analysis of bisulfite sequencing data obtained from 710
      alleles. Methylation at these centers was insignificant in normal epithelium,
      reached 80 to 90% in grade 4/5 PCa, but declined to less than 20% in bone
      metastases. In addition, progressive methylation spreading from the exonic CGI to
      the promoter CGI, which correlated with loss of ER-beta expression, was detected
      in microdissected samples and in cell cultures. Using a new class of methylated
      oligonucleotides that mediate sequence-specific methylation in cellulo, we
      demonstrated that methylation of the promoter CGI, but not the exonic CGIs, led
      to transcriptional inactivation of ER-beta. Our results present the first
      evidence that epigenetic regulation of ER-beta is a reversible and tumor stage
      specific process and that gene silencing via methylated oligonucleotides may have
      therapeutic potential in the treatment of advanced PCa.

PMID- 15161635
TI  - Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13
      receptor subunit expression in idiopathic interstitial pneumonia.
AB  - Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic
      pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIP), but
      it is not presently clear how this proliferative response by lung fibroblasts can
      be therapeutically modulated. In the present study, we examined whether it was
      possible to selectively target primary human pulmonary fibroblasts grown out of
      surgical lung biopsies (SLBs) from IIP patients based on their expression of
      interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines
      cultured from patients with the severest form of IIP, namely usual interstitial
      pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL
      13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines
      grown from other IIP SLBs and normal SLBs. When exposed to increasing
      concentrations of a chimeric protein comprised of human IL-13 and a truncated
      version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual
      interstitial pneumonia fibroblasts was inhibited to a much greater extent
      compared with fibroblast lines from nonspecific interstitial pneumonia and
      respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts
      from normal patients exhibited minimal susceptibility to the cytotoxic effect of
      IL13-PE. IL13-PE-mediated targeting of IIP fibroblasts was dependent on their
      expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the
      abnormal proliferative properties of human lung fibroblasts from certain IIP
      patient groups can be modulated in a manner that is dependent on the IL-4 and IL
      13 receptor subunit expression by these cells.

PMID- 15161637
TI  - Plasmodium falciparum-infected erythrocytes adhere both in the intervillous space
      and on the villous surface of human placenta by binding to the low-sulfated
      chondroitin sulfate proteoglycan receptor.
AB  - In pregnant women infected with Plasmodium falciparum, the parasite-infected red
      blood cells (IRBCs) sequester in the placenta through chondroitin 4-sulfate (C4S)
      mediated adherence. The pattern of IRBC adherence in P. falciparum-infected
      placenta has been controversial. Moreover, the identity of the chondroitin
      sulfate proteoglycan (CSPG) receptor, that mediates IRBC adherence, and its
      location in the placenta have not been established. This study, using
      immunohistochemical techniques, clearly shows, for the first time, that the low
      sulfated CSPGs of the placenta are localized predominantly in the intervillous
      space. Ex vivo IRBC adherence analyses demonstrate that the IRBCs are adhered to
      the CSPG receptors in the placenta in a C4S-dependent manner. This IRBC binding
      pattern was similar to that observed in P. falciparum-infected placentas. These
      data and the results of dual-fluorescence staining of the endogenous RBCs and
      syncytiotrophoblasts, and co-localization of CSPG and IRBC adherence
      unequivocally establish that the low-sulfated CSPGs are the major natural
      receptors for IRBC adherence in the placenta. Further, it was found that IRBCs
      adhere mainly in the intervillous space and also at significant levels to the
      syncytiotrophoblasts. Finally, the ex vivo IRBC adherence method described herein
      provides a reliable procedure for future studies for the assessment of the
      efficacy of C4S inhibitors and adhesion inhibitory antibodies.

PMID- 15161638
TI  - Keratinocytes from patients lacking collagen XVII display a migratory phenotype.
AB  - Acquired or inherited junctional epidermolysis bullosa are skin diseases
      characterized by a separation between the epidermis and the dermis. In inherited
      nonlethal junctional epidermolysis bullosa, genetic analysis has identified
      mutations in the COL17A1 gene coding for the transmembrane collagen XVII whereas
      patients with acquired diseases have autoantibodies against this protein. This
      suggests that collagen XVII participates in the adhesion of basal keratinocytes
      to the extracellular matrix. To test this hypothesis, we studied the behavior of
      keratinocytes with null mutations in the COL17A1 gene. Initial adhesion of mutant
      cells to laminin 5 was comparable to controls and similarly dependent on
      alpha3beta1 integrins. The spreading of mutant cells was, however, enhanced,
      suggesting a propensity to migrate, which was confirmed by migration assays. In
      addition, laminin 5 deposited by collagen XVII-deficient keratinocytes was
      scattered and poorly organized, suggesting that correct integration of laminin 5
      within the matrix requires collagen XVII. This assumption was supported by the co
      distribution of the two proteins in the matrix of normal human keratinocytes and
      by protein-protein-binding assays showing that the C-terminus of collagen XVII
      binds to laminin 5. Together, the results unravel an unexpected role of collagen
      XVII in the regulation of keratinocyte migration.

PMID- 15161639
TI  - Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse
      melanoma cells.
AB  - Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be
      involved in colorectal carcinoma metastasis with an unknown mechanism. Here we
      demonstrated that PRL-3 expression was up-regulated in human liver carcinoma
      compared with normal liver. PRL-3 was also highly expressed in metastatic
      melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16
      cells. B16 cells transfected with PRL-3 cDNA displayed morphological
      transformation from epithelial-like shape to fibroblast-like shape. PRL-3
      overexpressed cells showed much higher migratory ability, which could be reversed
      by specific anti-sense oligodeoxynucleotide and the phosphatase inhibitors sodium
      orthovanadate or potassium bisperoxo oxovanadate V. Meanwhile, the expression of
      the catalytically inactive PRL-3 mutations (D72A or C104S) significantly reduced
      the cell migratory capability. In addition, PRL-3 transfectants demonstrated
      altered extracellular matrix adhesive property and up-regulated integrin-mediated
      cell spreading efficiency. Furthermore, we confirmed that PRL-3 could facilitate
      lung and liver metastasis of B16 cells in an experimental metastasis model in
      mice, consistent with accelerated proliferation and growth rate both in vitro and
      in vivo. Together, these observations provide convincing evidence that PRL-3
      truly plays a causal role in tumor metastasis.

PMID- 15161640
TI  - Myofibroblast differentiation is induced in keratinocyte-fibroblast co-cultures
      and is antagonistically regulated by endogenous transforming growth factor-beta
      and interleukin-1.
AB  - In wound healing epidermal-dermal interactions are known to regulate keratinocyte
      proliferation and differentiation. To find out how fibroblasts respond to
      epithelial stimuli, we characterized fibroblasts in monolayer co-culture with
      keratinocytes. On co-culture numerous extracellular matrix- and smooth muscle
      cell-associated gene transcripts were up-regulated in fibroblasts, suggesting a
      differentiation into myofibroblasts. Increased alpha-smooth muscle actin (alpha
      SMA) protein expression in co-cultured fibroblasts started at approximately day
      4, was serum-independent, but required endogenous transforming growth factor
      (TGF)-beta. In co-cultures, TGF-beta neutralizing monoclonal antibody strongly
      reduced alpha-SMA induction. Endogenous TGF-beta production and activation were
      increased at 24 and 48 hours, requiring, like alpha-SMA induction, close
      keratinocyte-fibroblast proximity. As myofibroblast differentiation only started
      after 4 days, we analyzed the presence of endogenous inhibitors at early time
      points. Blocking keratinocyte-derived interleukin (IL)-1 using IL-1 receptor
      antagonist, alpha-SMA expression in co-cultures was potentiated. Conversely,
      adding exogenous IL-1alpha completely suppressed endogenous alpha-SMA induction.
      In co-cultured fibroblasts strong nuclear factor-kappaB binding activity was
      observed from 2 hours, decreasing at 2 and 4 days, suggesting an early, IL-1
      mediated inhibition of TGF-beta signaling in co-cultured fibroblasts. This
      biphasic differentiation event is regulated by the balance of endogenous TGF-beta
      and IL-1 activity and is reminiscent of myofibroblast differentiation at early
      and later stages of wound healing.

PMID- 15161641
TI  - Increased apoptosis and inflammation after focal brain ischemia in mice lacking
      connexin43 in astrocytes.
AB  - Astrocytes secrete cytokines and neurotrophic factors to neurons, consistent with
      a neurosupportive role for astrocytes. However, in ischemic or metabolic insults,
      the function of astrocytic gap junctions composed mainly from connexin43 (Cx43)
      remains controversial. We have previously shown that heterozygous Cx43 null mice
      subjected to middle cerebral artery occlusion exhibited significantly enhanced
      stroke volume and apoptosis compared to wild-type mice. In this study, we used
      mice in which the human GFAP promoter-driven cre transgene deletes the floxed
      Cx43 gene in astrocytes, excluding the effects from reduced Cx43 expression in
      many other cell types as well as astrocytes. We induced focal brain ischemia in
      mice lacking Cx43 in astrocytes [Cre(+)] and control littermates [Cre(-)]. Cre(+)
      mice showed a significantly increased stroke volume and enhanced apoptosis,
      detected by terminal dUTP nick-end labeling and caspase-3 immunostaining,
      compared to Cre(-) mice. Inflammatory response assessed by the microglial marker
      CD11b was amplified in the penumbra of Cre(+) mice compared to that of Cre(-)
      mice. Our results suggest that astrocytic gap junctions could be important for
      the regulation of neuronal apoptosis and the inflammatory response after stroke.
      These findings support the view that astrocytes play a critical role in
      neuroprotection during ischemic insults.

PMID- 15161643
TI  - Macrophage/microglial accumulation and proliferating cell nuclear antigen
      expression in the central nervous system in human immunodeficiency virus
      encephalopathy.
AB  - This study was performed to quantitate and characterize the mononuclear
      phagocytes (MPs) in human immunodeficiency virus encephalopathy (HIVE) by
      immunohistochemistry in an effort to gain insights into potential mechanisms of
      central nervous system (CNS) accumulation. Single- and double-labeled studies
      using antibodies against CD14, CD16, CD68, proliferating cell nuclear antigen
      (PCNA), Ki-67, von Willebrand factor, and HIV-1 p24 were performed using brain
      tissue from patients with HIVE, HIV-1 infection without encephalitis, and
      seronegative controls. A substantial increase in MPs was observed in CNS tissue
      from patients with HIVE, relative to seronegative controls and patients with
      acquired immune deficiency syndrome but without encephalitis, as determined by
      CD68 and CD16 immunohistochemistry. A large proportion of CD16+ MPs in HIVE CNS
      tissue were PCNA+, but do not appear to be proliferating, based on limited Ki-67
      positivity. Although virtually all cells positive for HIV-1 p24 were PCNA+, there
      were many PCNA+ cells where HIV-1 p24 expression was not detected. PCNA
      positivity was also observed in some endothelial cells and ependymal cells in
      HIVE CNS. Our results would support a role for HIV-1-induced alterations in MP
      trafficking and homeostasis in the pathogenesis of HIVE.

PMID- 15161644
TI  - Endometrial angiopoietin expression and modulation by thrombin and steroid
      hormones: a mechanism for abnormal angiogenesis following long-term progestin
      only contraception.
AB  - The angiopoietins (Ang) are endothelial cell-related factors necessary for the
      development and maintenance of all vessels. Altering the expression of these
      proteins would be expected to result in aberrant angiogenesis. Indeed the fragile
      endometrial vasculature and bleeding observed in women treated with long-term
      progestin-only contraceptives has been associated with changes in the expression
      of Ang-1 and Ang-2. Since bleeding would result in thrombin formation, we have
      assessed the effects of thrombin on the expression of the Angs in human
      endometrial cells. This study shows that thrombin significantly reduces the
      expression of Ang-1 protein and mRNA expression in human endometrial stromal
      cells (HESCs) and minimally decreases the production of Ang-2 protein in human
      endometrial endothelial cells (HEECs). Hence the presence of thrombin due to
      aberrant bleeding could affect the angiogenic potential of the endometrium,
      creating a feed forward loop resulting in more thrombin, weak vasculature, and
      more bleeding. In addition, since the exact localization of Ang in the human
      endometrium remains a subject of controversy, we have addressed this issue in an
      in vivo system by analyzing the expression of Angs by microdissection of HESCs,
      HEECs, and human endometrial glandular epithelial cells followed by real time,
      quantitative RT-PCR.

PMID- 15161642
TI  - Role of leukocyte elastase in preventing cellular re-colonization of the mural
      thrombus.
AB  - To explore possible mechanisms responsible for the absence of cell re
      colonization of mural thrombi in aneurysms, we analyzed the release and storage
      of leukocyte proteases in the most luminal layer versus intermediate and
      abluminal layers of 10 mural thrombi of human abdominal aortic aneurysms. The
      luminal layer contained many polymorphonuclear leukocytes (PMNs), which released
      pro-matrix metalloproteinase (MMP)-9 and MMP-8. Leukocyte elastase was also
      stored and released by the luminal layer (immunohistochemistry, activity on
      synthetic substrates, and casein zymography). Acid buffer allowed extraction of
      leukocyte elastase from the luminal layer, which was inhibited by elastase
      inhibitors. Casein zymography of luminal extracts and conditioned medium from
      formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs exhibited a similar
      lysis pattern, corresponding to elastase activity. Smooth muscle cell (SMC)
      seeding resulted in colonization of the intermediate thrombus layer ex vivo but
      not of the luminal layer. Extracts of the luminal layer induced loss of anchorage
      of both cultured human smooth muscle cells and stromal cells of bone marrow
      origin (anoikis). This anoikis was prevented by preincubation of the extracts
      with serine protease inhibitors. Moreover, adhesion of human SMCs and stromal
      bone marrow cells on fibrin gels was strongly inhibited when the gel was
      preincubated with pure elastase, medium of fMLP-stimulated PMNs, or extracts of
      luminal layers of mural thrombi. This loss of cell anchorage was prevented by the
      preincubation of the medium or extracts with alpha(1)-antitrypsin, but not when
      alpha(1)-antitrypsin was added after binding of elastase to the fibrin gel. In
      conclusion, elastase released by PMNs trapped within the mural thrombus impairs
      the spontaneous anchorage of mesenchymal cells to a fibrin matrix. This
      phenomenon could be one mechanism by which cellular healing of the mural thrombus
      in aneurysms is prevented.

PMID- 15161645
TI  - Vascular apolipoprotein e expression and recruitment from circulation to modulate
      smooth muscle cell response to endothelial denudation.
AB  - Apolipoprotein E (apoE) has been shown previously to have anti-proliferative and
      anti-migratory effects on smooth muscle cells in culture. In addition,
      overexpression of the apoE gene also reduces neointimal hyperplasia in mice after
      endothelial denudation. In this investigation, immunohistochemical techniques
      were used to demonstrate that apoE was present in the medial smooth muscle layers
      of the carotid artery between 1 and 28 days after endothelial cell denudation.
      Analysis of transgenic mice overexpressing human apoE in the liver revealed that
      apoE was recruited from the circulation to the injured site of the vessel wall.
      In situ hybridization using a mouse-specific apoE mRNA probe confirmed that apoE
      was also synthesized in the carotid artery after endothelial denudation.
      Interestingly, apoE accumulation in apoE transgenic mice followed a layer
      specific pattern, and was inversely associated with smooth muscle alpha-actin
      expression. The vascular accumulation of apoE after endothelial denudation, and
      its association with alpha-actin-depleted smooth muscle cells, suggest that apoE
      inhibition of injury-induced neointimal hyperplasia is not due to the inhibition
      of injury-induced smooth muscle cell de-differentiation, but is likely a direct
      effect of apoE on smooth muscle cell migration and proliferation.

PMID- 15161646
TI  - Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac
      malformations.
AB  - NKX2-5 is a homeodomain-containing transcription factor important in cardiac
      development. Familial mutations in the NKX2-5 gene are associated with cardiac
      abnormalities, but mutations are rare in sporadic cases. We studied the pathology
      and molecular genetics of NKX2-5 in diseased heart tissues of 68 patients with
      complex congenital heart disease (CHD), particularly atrial (ASD), ventricular
      (VSD), and atrioventricular septal defects (AVSD). We also studied DNA extracted
      from 16 normal hearts, as well as lymphocytic DNA from 50 healthy volunteers, 7
      families, and 4 unrelated individuals with CHD. Direct sequencing revealed 53
      NKX2-5 mutations in the diseased heart tissues, including nonsynonymous
      substitutions in the homeodomain of NKX2-5. We found common mutations among
      unrelated patients, but certain mutations were specific to VSDs and AVSDs. Many
      patients had multiple NKX2-5 mutations, up to 14 nonsynonymous mutations per
      patient in VSDs. Importantly, these nonsynonymous mutations were mainly absent in
      normal heart tissues of the same CHD patients, thus indicating somatic origin and
      mosaicism of mutations. Further, observed mutations were completely absent in
      normal hearts and lymphocytic DNA of healthy individuals. Our findings provide
      new insights for somatic NKX2-5 mutations to be of importance in congenital heart
      disease.

PMID- 15161647
TI  - Inhibition of amyloid A amyloidogenesis in vivo and in tissue culture by 4-deoxy
      analogues of peracetylated 2-acetamido-2-deoxy-alpha- and beta-d-glucose:
      implications for the treatment of various amyloidoses.
AB  - Two novel sugars, 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-alpha- and beta-D
      xylo-hexopyranoses, have been synthesized and their effects on heparan sulfate
      biosynthesis using primary mouse hepatocytes in tissue culture have been
      assessed. At concentrations of 0.1 and 1.0 mmol/L a mixture of both anomers
      significantly inhibited the biosynthesis of heparan sulfate by 60% and 99%,
      respectively. At 1.0 mmol/L the average molecular weight of the heparan sulfate
      synthesized is reduced from 77 kd to 40 kd. The biosynthetic inhibition is
      apparent within 1 hour (the earliest time point examined) of exposure of the
      hepatocytes to the analogues and appears virtually complete throughout a 24-hour
      incubation period. Using a radiolabeled version of the beta-anomer we demonstrate
      that the analogue is incorporated into growing heparan sulfate chains. The nature
      of the analogue, the quantity of analogue isotope incorporated, and the reduction
      in the size of the heparan sulfate polysaccharide are consistent with UDP
      activation and incorporation of the analogue and truncation of the growing
      heparan sulfate chain. At 0.1 mmol/L, and in the presence of a constant
      concentration of serum amyloid A (the precursor to AA amyloid), each analogue
      inhibited amyloid deposition (by 95 to 99%) in a tissue culture model of AA
      amyloidogenesis. At 6 mg/dose twice daily each analogue inhibited in vivo splenic
      AA amyloid deposition by 65 to 70% when using a rapid induction model of mouse AA
      amyloidogenesis. These data indicate that polysaccharides, such as heparan
      sulfate, play an integral part in the pathogenesis of AA amyloid deposition, and
      potentially other forms of amyloid. These data support our previous work that
      demonstrated that agents that mimic aspects of heparan sulfate structure and that
      interfere with heparan sulfate:amyloid protein binding inhibit AA amyloid
      deposition. They emphasize that heparan sulfate likely plays a critical role in
      amyloidogenesis, and compounds that interfere with heparan sulfate biosynthesis
      may provide leads for the development of anti-amyloid therapeutic agents.

PMID- 15161649
TI  - alpha-internexin is present in the pathological inclusions of neuronal
      intermediate filament inclusion disease.
AB  - Neuronal intermediate filament (IF) inclusion disease (NIFID) is a novel
      neurological disease of early onset with a variable clinical phenotype including
      frontotemporal dementia, pyramidal, and extrapyramidal signs. Pathologically, in
      affected areas, there is neuronal loss, astrocytosis, and neuronal
      intracytoplasmic aggregates of abnormal neuronal IFs that contain neither tau nor
      alpha-synuclein. Thus, to characterize the neuronal IF protein profile of
      inclusions in NIFID, immunohistochemistry (IHC) was performed on 10 cases of
      NIFID, four normal aged controls (NL), and two cases of Alzheimer's disease (AD)
      using a panel of anti-neuronal IF proteins. Immunoelectron microscopy was
      performed on selected cases and frozen tissue from the frontal lobe of four cases
      was used for biochemical studies including sequential extractions and Western
      blotting. Based on these studies, we report here for the first time that alpha
      internexin, a neuronal IF protein, is present within the inclusions of NIFID as
      are all three neurofilament subunits: heavy, medium, and light. Thus, all class
      IV neuronal IF proteins are present within the pathological inclusions of this
      disease. Biochemistry revealed that IF aggregates were soluble in sodium dodecyl
      sulfate (SDS) and no post-translational modification was detected when compared
      with Alzheimer's disease or aged control brains. Hence, we conclude that NIFID is
      characterized by the pathological cytoplasmic aggregation of all class IV
      neuronal IF proteins in brain. The discovery of alpha-internexin in the
      cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and
      other neurological diseases with pathological accumulations of IFs.

PMID- 15161648
TI  - Neuropilin-1 in human colon cancer: expression, regulation, and role in induction
      of angiogenesis.
AB  - Neuropilin-1 (NRP-1), a recently identified co-receptor for vascular endothelial
      growth factor, is expressed by several nongastrointestinal tumor types and
      enhances prostate cancer angiogenesis and growth in preclinical models. We
      investigated the expression and regulation of NRP-1 and the effect of NRP-1
      overexpression on angiogenesis and growth of human colon adenocarcinoma by
      immunohistochemistry and in situ hybridization. NRP-1 was expressed in 20 of 20
      human colon adenocarcinoma specimens but not in the adjacent nonmalignant colonic
      mucosa. By reverse transcriptase-polymerase chain reaction analysis, NRP-1 mRNA
      was expressed in seven of seven colon adenocarcinoma cell lines. Subcutaneous
      xenografts of stably transfected KM12SM/LM2 human colon cancer cells
      overexpressing NRP-1 led to increased tumor growth and angiogenesis in nude mice.
      In in vitro assays, conditioned medium from NRP-1-transfected cell lines led to
      an increase in endothelial cell migration, but did not affect endothelial cell
      growth. Epidermal growth factor (EGF) led to induction of NRP-1 in human colon
      adenocarcinoma cells and selective blockade of the epidermal growth factor
      receptor (EGFR) decreased constitutive and EGF-induced NRP-1 expression. Blockade
      of the Erk 1/2 and P38 mitogen-activated protein kinase signaling pathways also
      led to a decrease in constitutive and EGF-induced NRP-1 expression. These
      findings demonstrate the ubiquitous expression of NRP-1 in human colon cancer and
      suggest that NRP-1 may contribute to colon cancer angiogenesis and growth. This
      study also suggests that EGF and mitogen-activated protein kinase signaling
      pathways play an important role in NRP-1 regulation in colon cancer cells.

PMID- 15161650
TI  - Acetylcholinesterase-Abeta complexes are more toxic than Abeta fibrils in rat
      hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive
      astrocytosis, and neuronal cell loss.
AB  - Neuropathological changes generated by human amyloid-beta peptide (Abeta) fibrils
      and Abeta-acetylcholinesterase (Abeta-AChE) complexes were compared in rat
      hippocampus in vivo. Results showed that Abeta-AChE complexes trigger a more
      dramatic response in situ than Abeta fibrils alone as characterized by the
      following features observed 8 weeks after treatment: 1). amyloid deposits were
      larger than those produced in the absence of AChE. In fact, AChE strongly
      stimulates rat Abeta aggregation in vitro as shown by turbidity measurements,
      Congo Red binding, as well as electron microscopy, suggesting that Abeta-AChE
      deposits observed in vivo probably recruited endogenous Abeta peptide; 2). the
      appearance of laminin expressing neurons surrounding Abeta-AChE deposits (such
      deposits are resistant to disaggregation by laminin in vitro); 3). an extensive
      astrocytosis revealed by both glial fibrillary acidic protein immunoreactivity
      and number counting of reactive hypertrophic astrocytes; and 4). a stronger
      neuronal cell loss in comparison with Abeta-injected animals. We conclude that
      the hippocampal injection of Abeta-AChE complexes results in the appearance of
      some features reminiscent of Alzheimer-like lesions in rat brain. Our studies are
      consistent with the notion that Abeta-AChE complexes are more toxic than Abeta
      fibrils and that AChE triggered some of the neurodegenerative changes observed in
      Alzheimer's disease brains.

PMID- 15161651
TI  - Influence of native and hypochlorite-modified low-density lipoprotein on gene
      expression in human proximal tubular epithelium.
AB  - Inflammatory infiltrates can modify (lipo)proteins via hypochlorous
      acid/hypochlorite (HOCl/OCl(-)) an oxidant formed by the myeloperoxidase-H(2)O(2)
      halide system. These oxidatively modified proteins emerge in tubuli in some
      proteinuric and interstitial diseases. Human proximal tubular cells (HK-2) were
      used to confirm the hypothesis of detrimental and differential impact of HOCl
      modified low density lipoprotein (HOCl-LDL), an in vivo occurring lipoprotein
      modification exerting proatherogenic and proinflammatory capacity. HOCl-LDL
      showed dose-dependent antiproliferative effects in HK-2 cells. Small dedicated
      cDNA macroarrays were used to identify differentially regulated genes. A rapid
      increase in the expression of genes involved in reactive oxygen species
      metabolism and cell stress, eg, heme oxygenase-1, thioredoxin reductase,
      cytochrome b5 reductase, Gadd 153, amino acid transporter E16, and HSP70 was
      found after HOCl-LDL treatment of HK-2 cells. In parallel, genes involved in
      tissue remodeling and inflammation eg, CTGF, VCAM-1, IL-1beta, MMP7, and VEGF
      were up-regulated. Quantitative RT-PCR verified differential expression of a
      subset of these genes in microdissected tubulointerstitia from patients with
      acute tubular damage, progressive proteinuric renal disease, and membranous
      glomerulonephritis (with declining renal function), but not in stable patients
      with proteinuria caused by minimal change disease. The demonstration of selective
      up-regulation of a subgroup of genes if proteinuria is accompanied by the
      presence of HOCl-modified (lipo)proteins support the potential pathophysiological
      role of the myeloperoxidase-H(2)O(2)-halide system and HOCl-LDL in renal disease.

PMID- 15161653
TI  - Pivotal role of cathepsin K in lung fibrosis.
AB  - The paramount importance of the homeostasis of the extracellular matrix for
      pulmonary function is exemplified by two opposing extremes: emphysema and
      pulmonary fibrosis. This study examined the putative role of cathepsin K (catK)
      in the pathology of lung fibrosis in mice and its relevance to the human disease
      activity. We compared the induction of lung fibrosis by administration of
      bleomycin. CTSK(-/-) mice deposited significantly more extracellular matrix than
      control mice. Primary lung fibroblasts derived from CTSK(-/-) mice showed a
      decreased collagenolytic activity indicating the role of catK in collagen
      degradation. Interestingly, CTSK(+/+) control mice revealed an increased
      expression of catK in fibrotic lung regions suggesting a protective role of catK
      to counter the excessive deposition of collagen matrix in the diseased lung.
      Similarly, in lung specimens obtained from patients with lung fibrosis
      fibroblasts expressed larger amounts of catK than those obtained from normal
      lungs. Activation of human pulmonary fibroblasts in primary cell cultures led to
      an increased activity of catK through enhanced gene transcription and protein
      expression and to increased intracellular collagenolytic activity. We believe
      that this is the first study to show that catK plays a pivotal role in lung
      matrix homeostasis under physiological and pathological conditions.

PMID- 15161652
TI  - Kinetics of gene expression in murine cutaneous graft-versus-host disease.
AB  - The kinetics of gene expression associated with the development of cutaneous
      graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched
      allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from
      recipient mice with or without GVHD between 7 and 40 days after transplantation
      for histopathological analysis and gene expression profiling. Gene expression
      patterns were consistent with early infiltration and activation of CD8(+) T and
      mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The
      sequential infiltration and activation of effector cells correlated with the
      histopathological development of cutaneous GVHD and was accompanied by up
      regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and 
      10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules
      (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing
      and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of
      apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible
      genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast
      proliferation and matrix synthesis (interleukin-1beta, transforming growth factor
      beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and
      differentiation (small proline-rich proteins 2E and 1B). Many acute-phase
      proteins were up-regulated early in murine cutaneous GVHD including serum amyloid
      A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and
      metallothioneins 1 and 2. The kinetics of gene expression were consistent with
      the evolution of cutaneous pathology as well as with current models of disease
      progression during cutaneous GVHD.

PMID- 15161654
TI  - Differential expression of splicing variants of the human caldesmon gene (CALD1)
      in glioma neovascularization versus normal brain microvasculature.
AB  - Caldesmon is a cytoskeleton-associated protein which has not yet been related to
      neoplastic angiogenesis. In this study we investigated the expression of the
      caldesmon gene (CALD1) splicing variants and the protein expression level in
      glioma microvessels versus normal brain microvasculature. To exclude sources of
      splice variant expression from non-vascular components all possible cellular
      components present in control and glioma samples were pre-screened by laser
      capture microdissection followed by RT-PCR before the cohort study. We discovered
      differential expression of the splicing variants of CALD1 in the tumor
      microvessels in contrast to normal brain microvasculature. Missplicing of exons
      1, 1 + 4, and 1' + 4 of the gene is exclusively found in glioma microvessels. To
      exclude the possibility that this missplicing results from splice-site mutations,
      mutation scanning was performed by a coupled in vitro transcription/translation
      assay (IVTT). No premature stop mutations were traced by the IVTT. The
      transcriptional changes consequently resulted in up-regulation at the protein
      expression level. The up-regulated expression of caldesmon was coincident with
      the down-regulated expression of tight junction proteins (occludin and ZO-1). The
      results support the notion that missplicing of the CALD1 gene in glioma
      microvasculature is an independent epigenetic event regulated at the
      transcriptional level. The event coexists with tight junction (TJ) breakdown of
      the endothelial cells in glioma microvasculature. The data reveal a novel
      mechanism contributing to dysfunctionality of glioma neovascularization.

PMID- 15161655
TI  - Fibroblast growth factor enriches the embryonic liver cultures for hepatic
      progenitors.
AB  - Fibroblast growth factors (FGFs) play an important role in hepatic induction
      during development. The aim of our study was to investigate the effect of
      exogenous FGFs on ex vivo liver development. We begin our analysis by examining
      FGF signaling during early mouse liver development. Phospho-FGF receptor
      (Tyr653/654) was detected in embryonic day 10 (E10) to E12 livers only. Next, E10
      livers were cultured in the presence of FGF1, FGF4, or FGF8 for 72 hours and
      examined for histology, proliferation, apoptosis, and differentiation. FGFs
      especially FGF8 promoted sheet-like architecture, cell proliferation, and
      survival as compared to the control. All FGFs induced a striking increase in the
      number of c-kit and alpha-fetoprotein-positive progenitors, without altering
      albumin staining. However these progenitors were CK-19-positive (biliary and
      bipotential progenitor marker) only in the presence of FGF1 or FGF4 and not FGF8.
      FGFs also induced beta-catenin, a stem cell renewal factor in these cultures. In
      conclusion, the presence of activated FGFR indicates a physiological role of FGF
      during early liver development. FGF1 and FGF4 enrich the embryonic liver cultures
      for bipotential hepatic progenitors. FGF8 promotes such enrichment and induces a
      one-step differentiation toward a unipotential hepatocyte progenitor. Thus, FGFs
      might be useful for enrichment and propagation of developmental hepatic
      progenitors.

PMID- 15161656
TI  - Up-regulation of endothelial nitric oxide synthase inhibits pulmonary leukocyte
      migration following lung ischemia-reperfusion in mice.
AB  - Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory
      response in various organs. However, the role of nitric oxide synthase isoforms
      (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly
      understood. We therefore studied post-ischemic endothelial adhesion molecule
      expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice
      subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and
      mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO
      mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT
      mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung
      tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged.
      Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining
      an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial
      tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung
      tissue water content peaked at 5 hours of reperfusion and were found
      significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction
      was associated with pronounced up-regulation of vascular cell adhesion molecule
      (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS
      attenuates post-ischemic inflammatory injury to the lung most probably via
      inhibition of endothelial adhesion molecule expression.

PMID- 15161657
TI  - Signal transducer and activator of transcription-3 activation contributes to high
      tissue inhibitor of metalloproteinase-1 expression in anaplastic lymphoma kinase
      positive anaplastic large cell lymphoma.
AB  - The tissue inhibitor of metalloproteinase-1 (TIMP1) is expressed in a subset of
      malignant lymphomas and can inhibit tumor spread and promote cell survival.
      Recent data suggest that TIMP1 expression may be regulated by signal transducer
      and activator of transcription (STAT)-3. Thus, we tested the hypothesis that
      TIMP1 expression is related to STAT3 activation in lymphomas, with a focus on
      anaplastic large cell lymphomas (ALCLs), which are known to express high levels
      of phosphorylated/active STAT3 (pSTAT3). Specific inhibition of STAT3 with a
      dominant-negative construct led to concentration-dependent down-regulation of
      TIMP1 expression in two anaplastic lymphoma kinase (ALK)(+) ALCL cell lines,
      Karpas 299 and SU-DHL-1. Using cDNA microarrays, ALK(+) ALCL cell lines
      consistently expressed the highest TIMP1 level among 29 lymphoma cell lines of
      various subtypes. The association between TIMP1 expression and high level of
      STAT3 activation was validated by Western blots and immunostaining using
      antibodies specific for pSTAT3 and TIMP1. We further evaluated the relationship
      between TIMP1 expression and STAT3 activation in 43 ALCL tumors (19 ALK(+) and 24
      ALK(-)) using immunohistochemistry and a tissue microarray. The TIMP1(+) group
      had a mean of 64% pSTAT3(+) cells as compared to 23% pSTAT3(+) cells in the
      TIMP1(-) group (P = 0.002). As expected, TIMP1 positivity was higher in the
      ALK(+) group (15 of 19, 79%) compared with the ALK(-) group (5 of 24, 21%; P =
      0.0002) because NPM-ALK restricted to ALK(+) tumors was previously shown to
      activate STAT3. In conclusion, STAT3 directly contributes to the high level of
      TIMP1 expression in ALK(+) ALCL, and TIMP1 expression correlates with high level
      of STAT3 activation in ALCL. TIMP1, as a downstream target of STAT3, may mediate
      the anti-apoptotic effects of STAT3.

PMID- 15161658
TI  - Retinoblastoma protein is frequently absent or phosphorylated in anaplastic large
      cell lymphoma.
AB  - The possible role of retinoblastoma protein (Rb) in the pathogenesis of
      anaplastic large-cell lymphoma (ALCL) is unknown. We investigated Rb protein
      expression, both total (phosphorylated and underphosphorylated) and active
      (underphosphorylated), in four anaplastic lymphoma kinase (ALK)-positive ALCL
      cell lines (Karpas 299, JB-6, SU-DHL1, and SR-786) by Western blot analysis, and
      in 67 ALCL tumors (30 ALK-positive, 37 ALK-negative) using immunohistochemical
      methods. We also used fluorescence in situ hybridization and polymerase chain
      reaction methods to assess for loss of heterozygosity of the rb gene. The
      findings were correlated with apoptotic rate assessed by the terminal dUTP nick
      end labeling assay. Immunoblots showed high total Rb levels in Karpas 299, SU
      DHL1 and SR-786 and relatively lower levels in and JB-6. Underphosphorylated Rb
      was negative or expressed at low levels in all cell lines. In ALCL tumors, total
      Rb was detected in 44 (66%) and absent in 23 (34%). The mean apoptotic rate was
      3.2% in Rb-negative tumors compared with 2.7%, 2.2%, and 1.2% in tumors with
      <10%, 10 to 50%, and >50% Rb-positive cells, respectively (P = 0.2, Kruskall
      Wallis test). In a subset of 25 total Rb-positive tumors we assessed for
      underphosphorylated Rb, which was detected in 12 tumors. The detection of only
      total Rb in the remaining 13 tumors suggests that Rb was phosphorylated.
      Fluorescence in situ hybridization showed allelic loss of the rb gene in 10 (40%)
      of 25 tumors analyzed and was significantly associated with absence of Rb
      expression (P = 0.003). Similar results were obtained for loss of heterozygosity
      of the 13q14 locus. Five-year progression-free survival for patients with Rb
      negative ALCL was 89.4% compared with 47.7% for patients with total Rb-positive
      ALCL (P = 0.006, log-rank test). Similar trends for progression-free survival
      held true for patients with ALK-positive and ALK-negative tumors analyzed
      separately. In conclusion, Rb is absent or phosphorylated in most ALCL cell lines
      and tumors and absence of Rb expression is associated with better clinical
      outcome in patients with ALCL.

PMID- 15161659
TI  - Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient
      breast cancer.
AB  - In a search for signaling molecules that act downstream of E-cadherin
      inactivation in cancer, we examined the expression and localization of E-cadherin
      associated proteins in lobular carcinoma, in which the E-cadherin gene is
      frequently inactivated, and found that E-cadherin down-regulation correlated with
      the cytoplasmic localization of p120ctn. Similar cytoplasmic localization of
      p120ctn and growth factor-induced accumulation of tyrosine-phosphorylated p120ctn
      in the protrusive domain were observed in E-cadherin-deficient breast cancer
      cells. Down-regulation of endogenous p120ctn by RNA interference promoted stress
      fiber formation and induced a flattened morphology with an increase of Rho-GTPase
      activity; it also reduced the development of membranous protrusions and migratory
      activity in E-cadherin-deficient breast cancer cells. Inactivation of E-cadherin
      in cancer cells is associated with the conversion from epithelial to mesenchymal
      phenotype, which also occurs in physiological conditions such as developmental
      processes. Cytoplasmic localization of p120ctn accompanied by E-cadherin down
      regulation was observed in mesoderm cells that had undergone epithelial
      mesenchymal transition during early mouse embryogenesis. Collectively, our
      results suggest that cytoplasmic p120ctn may contribute to the invasive phenotype
      of E-cadherin-deficient breast cancer cells.

PMID- 15161660
TI  - Male infertility and DNA damage in Doppel knockout and prion protein/Doppel
      double-knockout mice.
AB  - The prion protein (PrP) and Doppel (Dpl) have many structural and biochemical
      properties in common, leading to the suggestion that the lack of an obvious
      phenotype in PrP-deficient mice maybe because of compensation by Dpl. To test
      this hypothesis and also investigate the function of Dpl we have generated Prnd(
      /-) and Prnp(-/-)/Prnd(-/-) mouse lines. Both develop normally and display an
      identical male sterility phenotype that differs from that reported for another
      Prnd(-/-) mouse line. Sperm from both our mutant lines were present at normal
      concentrations, had normal motility, and no morphological abnormalities. Despite
      only rarely fertilizing oocytes in vivo, because of an inability to perform the
      acrosome reaction, mutant sperm were capable of fertilization in vitro, albeit at
      reduced rates compared to wild type. Elevated levels of oxidative DNA damage were
      found in both types of mutant sperm and resulting embryos failed at an early
      stage. Therefore we found no evidence that Dpl compensates for the loss of PrP
      function in mutant mouse lines, but it does have an important anti-oxidant
      function necessary for sperm integrity and male fertility.

PMID- 15161662
TI  - Plasminogen mediates the pathological effects of urokinase-type plasminogen
      activator overexpression.
AB  - Increased expression of urokinase-type plasminogen activator (uPA) and its
      receptor (uPAR) is associated with different pathological conditions. Both uPAR
      mediated signaling and plasmin-catalyzed extracellular proteolysis may contribute
      to pathogenesis. To evaluate the involvement of plasminogen in such
      circumstances, we have taken advantage of transgenic mouse models in which
      overexpression of uPA and/or uPAR in enamel epithelium, basal epidermis, and hair
      follicles leads to a pathological phenotype; uPA transgenic mice have chalky
      white incisors and, when uPAR is co-expressed, develop extensive alopecia,
      epidermal thickening, and subepidermal blisters. We report here that when these
      transgenic mice were backcrossed into a plasminogen-deficient (Plg-/-)
      background, the dental and skin phenotypes appeared completely normal.
      Heterozygous Plg+/- transgenic mice exhibited a haplo-insufficiency, with an
      intermediate or normal phenotype. These results do not argue in favor of a role
      for uPAR-mediated signaling in our experimental model; rather, they demonstrate
      an essential, dose-dependent, requirement for plasminogen in uPA-mediated tissue
      alterations. They also support the hypothesis that plasminogen could play a part
      in certain skin diseases.

PMID- 15161661
TI  - Inhibition of intimal hyperplasia in transgenic mice conditionally expressing the
      chemokine-binding protein M3.
AB  - Chemokines have been implicated in the pathogenesis of a wide variety of
      diseases. This report describes the generation of transgenic mice that
      conditionally express M3, a herpesvirus protein that binds and inhibits
      chemokines. In response to doxycycline, M3 expression was induced in a variety of
      tissues and M3 was detectable in the blood by Western blotting. No gross or
      histological abnormalities were seen in mice expressing M3. To determine whether
      M3 expression could modify a significant pathophysiological response, we examined
      its effect on the development of intimal hyperplasia in response to femoral
      arterial injury. Intimal hyperplasia is thought to play a critical role in the
      development of restenosis after percutaneous transluminal coronary angioplasty
      and in the progression of atherosclerosis. Induction of M3 expression resulted in
      a 67% reduction in intimal area and a 68% reduction in intimal/medial ratio after
      femoral artery injury. These data support a role for chemokines in regulating
      intimal hyperplasia and suggest that M3 may be effective in attenuating this
      process. This transgenic mouse model should be a valuable tool for investigating
      the role of chemokines in a variety of pathological states.

PMID- 15161664
TI  - Targeted delivery of adenoviral vectors by cytotoxic T cells.
AB  - Effective targeting of vectors to tumor cells that have metastasized to multiple
      different tissue sites remains a major challenge for gene therapy. Tumor-specific
      cytotoxic T lymphocytes (CTLs) have been shown in animal models and in humans to
      be able to cross tissue barriers and traffic to tumor cells. However, their
      capacity to eliminate malignancy has been limited by tumor immune evasion
      strategies. We now use a model of Epstein-Barr virus-mediated malignancy to show
      that human CTLs themselves may be modified to release therapeutic vectors
      following engagement of their antigen-specific receptors and that these vectors
      will effectively transduce and destroy tumor targets. We generated EBV-specific
      CTLs that were transgenic for the adenoviral E1 gene under the control of the
      cell activation-dependent CD40 ligand (CD40L) promoter. Following transduction
      with E1-deficient adenoviral vectors, these CTLs produced infectious virus when
      exposed to HLA-matched EBV-expressing targets, but not on exposure to major
      histocompatibility complex (MHC)-mismatched or otherwise irrelevant cells. This
      approach provides a means of delivering oncolytic/therapeutic vectors not only to
      locally accessible macroscopic tumors as is presently the case, but also to
      disseminated metastatic disease, while avoiding the risks associated with
      systemic administration of large doses of adenoviral vectors.

PMID- 15161665
TI  - Antioxidative stress-associated genes in circulating progenitor cells: evidence
      for enhanced resistance against oxidative stress.
AB  - Adult and embryonic stem cells hold great promise for regenerative medicine.
      Expression profiling of stem cells revealed a characteristic imprint of genes, so
      called "stemness" genes, providing resistance to stress. Circulating progenitor
      cells with an endothelial phenotype (EPCs) can be isolated from peripheral blood
      and contribute to neovascularization and endothelial regeneration. We
      investigated whether EPCs are equipped with an antioxidative defense to provide
      resistance against oxidative stress. EPCs exhibited a significantly lower basal
      reactive oxygen species (ROS) concentration as compared with mature umbilical
      vein endothelial cells (HUVECs). Incubation with H(2)O(2) (500 microM) or the
      redox cycler LY-83583 (10 microM) profoundly increased the ROS concentration to 3
      and 4-fold and induced apoptosis in HUVECs. In contrast, H(2)O(2) and LY-83583
      induced only a minor increase in intracellular ROS levels and apoptosis in EPCs.
      Consistently, the expression of the intracellular antioxidative enzymes catalase,
      glutathione peroxidase and manganese superoxide dismutase (MnSOD), was
      significantly higher in EPCs versus HUVECs and human microvascular endothelial
      cells. In accordance, combined inhibition of these antioxidative enzymes
      increased ROS levels in EPCs and impaired EPC survival and migration. Taken
      together, EPCs reveal a higher expression of antioxidative enzymes and, thus, are
      exquisitely equipped to be protected against oxidative stress consistent with
      their progenitor cell character.

PMID- 15161666
TI  - Integrin alpha4beta7 and its counterreceptor MAdCAM-1 contribute to hematopoietic
      progenitor recruitment into bone marrow following transplantation.
AB  - Previous studies have shown that alpha4beta1 (very late activation antigen-4 [VLA
      4]) and vascular cell adhesion molecule-1 (VCAM-1) play a major role in
      hematopoietic progenitor cell (HPC) homing to bone marrow (BM). However, the
      antibody used to block VLA-4 function in the mouse (hybridoma clone PS/2) is not
      specific to VLA-4 but inhibits both alpha4beta1 and alpha4beta7 integrins. Here
      we have evaluated the contribution of alpha4beta7 in HPC homing to BM.
      Lineage(neg)Sca-1(pos)c-kit(pos) cells from adult mouse BM and the factor
      dependent cell progenitor (FDCP)-mix progenitor cell line express similar levels
      of alpha4beta7 by flow cytometry. The alpha4beta7 complex was functional since
      the chemokine CXCL12 enhanced the adhesion of FDCP-mix to immobilized mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1) and this was completely abrogated
      by anti-alpha4beta7 (hybridoma clone DATK32) or anti-alpha4 integrins (PS/2). BM
      intravital microscopy revealed that alpha4beta7 plays a predominant role in
      initial tethering and rolling but not in firm adhesion of FDCP-mix cells. Using
      homing assays, we demonstrate that alpha4beta7 on HPCs contributes to about half
      of all alpha4 integrin-mediated homing activity following BM transplantation.
      MAdCAM-1 is likely expressed since its inhibition significantly reduced HPC
      homing. Although there may be other alpha4beta7 integrin ligands involved (eg,
      fibronectin and VCAM-1), these data thus suggest that alpha4beta7 and its
      counterreceptor MAdCAM-1 represent a novel adhesion pathway mediating HPC homing
      to BM.

PMID- 15161663
TI  - Peroxisome proliferators and peroxisome proliferator-activated receptor alpha:
      biotic and xenobiotic sensing.

PMID- 15161668
TI  - A urokinase-activated recombinant diphtheria toxin targeting the granulocyte
      macrophage colony-stimulating factor receptor is selectively cytotoxic to human
      acute myeloid leukemia blasts.
AB  - Novel agents to treat acute myeloid leukemia (AML) are needed with increased
      efficacy and specificity. We have synthesized a dual-specificity fusion toxin
      DTU2GMCSF composed of the catalytic and translocation domains of diphtheria toxin
      (DT) fused to the granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      which the DT furin cleavage site 163RVRRSV170 is modified to a urokinase
      plasminogen activator (uPA) cleavage site 163GSGRSA170, termed U2. DTU2GMCSF was
      highly toxic to the TF1-vRaf AML cell line (proliferation inhibition assay; IC50
      = 3.14 pM), and this toxicity was greatly inhibited following pretreatment with
      anti-uPA and anti-GM-CSF antibodies. The activity of this toxin was then tested
      on a larger group of 13 human AML cell lines; 5 of the 13 cell lines were
      sensitive to DTU2GMCSF. An additional 5 of the 13 cell lines became sensitive
      when exogenous pro-uPA was added. Sensitivity to DTU2GMCSF strongly correlated
      with the expression levels of uPA receptors (uPARs) and GM-CSF receptors (GM
      CSFRs) as well as with total uPA levels. DTU2GMCSF was less toxic to normal cells
      expressing uPAR or GMCSFR alone, that is, human umbilical vein endothelial cells
      and peripheral macrophages, respectively. These results indicate that DTU2GMCSF
      may be a selective and potent agent for the treatment of patients with AML.

PMID- 15161667
TI  - The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug
      resistance in multiple myeloma by geranylgeranylation of Rho protein and
      activation of Rho kinase.
AB  - Primary drug resistance is a major problem in multiple myeloma, an incurable
      disease of the bone marrow. Cell adhesion-mediated drug resistance (CAM-DR)
      causes strong primary resistance. By coculturing multiple myeloma cells with bone
      marrow stromal cells (BMSCs), we observed a CAM-DR of about 50% to melphalan,
      treosulfan, doxorubicin, dexamethasone, and bortezomib, which was not reversed by
      secreted soluble factors. Targeting the adhesion molecules lymphocyte function
      associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) by monoclonal
      antibodies or by the LFA-1 inhibitor LFA703 reduced CAM-DR significantly. Only
      statins such as simvastatin and lovastatin, however, were able to completely
      restore chemosensitivity. All these effects were not mediated by deadhesion or
      reduced secretion of interleukin 6. Targeting geranylgeranyl transferase (GGTase)
      and Rho kinase by specific inhibitors (GGTI-298 and Y-27632), but not inhibition
      of farnesyl transferase (FTase) by FTI-277, showed similar reduction of CAM-DR.
      Addition of geranylgeranyl pyrophosphate (GG-PP), but not of farnesyl
      pyrophosphate (F-PP), was able to inhibit simvastatin-induced CAM-DR reversal.
      Our data suggest that the 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)/GG
      PP/Rho/Rho-kinase pathway mediates CAM-DR and that targeting this pathway may
      improve the efficacy of antimyeloma therapies by reduction of CAM-DR.

PMID- 15161669
TI  - Familial risk of lymphoproliferative tumors in families of patients with chronic
      lymphocytic leukemia: results from the Swedish Family-Cancer Database.
AB  - The importance of genetic factors in etiology of chronic lymphocytic leukemia
      (CLL) is suggested by family and population studies. However, the spectrum of
      malignancies sharing common genetic factors with CLL and the effects of sex and
      age on familial risk are unknown. We used the Swedish Family-Cancer Database to
      test for increased familial risks of CLL and other lymphoproliferative tumors.
      Cancer diagnoses from 1958 to 1998 were assessed in 14 336 first-degree relatives
      of 5918 CLL cases and in 28 876 first-degree relatives of 11 778 controls. Cancer
      risks in relatives of cases were compared with those in relatives of controls
      using marginal survival models. Relatives of cases were at significantly
      increased risk for CLL (relative risk [RR] = 7.52; 95% confidence interval [CI],
      3.63-15.56), for non-Hodgkin lymphoma (RR = 1.45; 95% CI, 0.98-2.16), and for
      Hodgkin lymphoma (RR = 2.35; 95% CI, 1.08-5.08). CLL risks were similar in
      parents, siblings, and offspring of cases, in male and female relatives, and were
      not affected by the case's age at diagnosis. Anticipation was not significant
      when analyzed using life table methods. We conclude that the familial component
      of CLL is shared with other lymphoproliferative malignances, suggesting common
      genetic pathways. However, because clinically diagnosed CLL is uncommon, absolute
      excess risk to relatives is small.

PMID- 15161670
TI  - Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor
      regressions in cutaneous lymphomas.
AB  - Primary cutaneous lymphomas have been successfully treated with interferons
      (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase
      1, open-label, dose-escalating trial of repeated intratumoral administration of
      TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and
      multilesional cutaneous B-cell lymphomas (CBCLs). TG1042 is a third-generation,
      nonreplicating human adenovirus vector containing a human IFN-gamma cDNA insert.
      Nine patients (7 CTCL, 2 CBCL) were enrolled at the following TG1042 doses: 3 x
      10(9), 3 x 10(10), and 3 x 10(11) total particles. Local clinical response was
      observed in 5 of 9 treated patients (3 patients with complete response [CR] and 2
      patients with partial response [PR]). Out of these, 3 patients showed systemic CR
      with the clearance of other noninjected skin lesions. Clinical response lasted
      for a median of 3 months (range, 1-6 months). Adverse events were mostly of
      grades 1 and 2. Seven of 9 treated patients had a detectable TG1042-derived IFN
      gamma message in injected lesions after the first treatment cycle. A TG1042-IFN
      gamma message was also detectable after several treatment cycles. We demonstrate
      the induction of humoral immune response to lymphoma tumor-antigen se70-2 after
      treatment. Our study shows that intralesional injections of TG1042 are both safe
      and well tolerated.

PMID- 15161671
TI  - Cholesterol synthesis and import contribute to protective cholesterol increments
      in acute myeloid leukemia cells.
AB  - Cholesterol levels are abnormally increased in many acute myeloid leukemia (AML)
      samples exposed in vitro to chemotherapy. Blocking these acute cholesterol
      responses selectively sensitizes AML cells to therapeutics. Thus, defining the
      molecular mechanisms by which AML cells accomplish these protective cholesterol
      increments might elucidate novel therapeutic targets. We now report that the
      levels of mRNAs encoding the cholesterol synthesis-regulating enzyme, 3-hydroxy-3
      methylglutaryl coenzyme A reductase, and the cholesterol-importing low-density
      lipoprotein (LDL) receptor were both increased by daunorubicin (DNR) or
      cytarabine (ARA-C) treatments in almost three fourths of cultured AML samples.
      However, less than one third of AML samples significantly increased LDL
      accumulation during drug treatments, suggesting that de novo synthesis is the
      primary mechanism by which most AML cells increase cholesterol levels during drug
      exposures. LDL increments were not correlated with cholesterol increments in ARA
      C-treated AML samples. However, LDL and cholesterol increments did correlate in
      DNR-treated AML samples where they were measured, suggesting that a subset of
      AMLs may rely on increased LDL accumulation during treatment with particular
      drugs. Our data suggest that cholesterol synthesis inhibitors may improve the
      efficacy of standard antileukemia regimens, but that for maximum benefit, therapy
      may need to be tailored for individual patients with leukemia.

PMID- 15161672
TI  - Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to
      domain 5 of high molecular weight kininogen.
AB  - We have shown that human high molecular weight kininogen is proangiogenic due to
      release of bradykinin. We now determined the ability of a murine monoclonal
      antibody to the light chain of high molecular weight kininogen, C11C1, to inhibit
      tumor growth compared to isotype-matched murine IgG. Monoclonal antibody C11C1
      efficiently blocks binding of high molecular weight kininogen to endothelial
      cells in a concentration-dependent manner. The antibody significantly inhibited
      growth of human colon carcinoma cells in a nude mouse xenograft assay and was
      accompanied by a significant reduction in the mean microvascular density compared
      to the IgG control group. We also showed that a hybridoma producing monoclonal
      antibody C11C1 injected intramuscularly exhibited markedly smaller tumor mass in
      a syngeneic host compared to a hybridoma producing a monoclonal antibody to the
      high molecular weight kininogen heavy chain or to an unrelated plasma protein. In
      addition, tumor inhibition by purified monoclonal antibody C11C1 was not due to
      direct antitumor effect because there was no decrease of tumor cell growth in
      vitro in contrast to the in vivo inhibition. Our results indicate that monoclonal
      antibody C11C1 inhibits angiogenesis and human tumor cell growth in vivo and has
      therapeutic potential for treatment of human cancer.

PMID- 15161673
TI  - Differential regulation of gene expression following CD40 activation of leukemic
      compared to healthy B cells.
AB  - It is possible to differentiate malignant from healthy cells and to classify
      diseases based on identification of specific gene expression profiles. We
      hypothesized that gene expression profiling could also be used to identify
      differential activation of healthy and malignant cells, and as a model for this,
      we examined the molecular sequelae of CD40 activation of healthy and B-cell
      chronic lymphocytic leukemia (CLL) cells. Hierarchical clustering analysis of
      gene expression signatures grouped samples by CD40 activation status and further
      subclassified CD40-activated CLL cells from healthy B cells. Supervised analyses
      in healthy B cells compared to CLL cells identified differential regulation of
      genes governing cell cycle progression and apoptosis. CD40 signaling of CLL cells
      increases their susceptibility to immune recognition, but promotes survival and
      cell cycle arrest, making these cells potentially more resistant to chemotherapy.
      These results illustrate the utility of gene expression profiling to elucidate
      the molecular sequelae of signaling in healthy cells and altered signaling
      pathways in malignant cells. This type of approach should be useful to identify
      targets of therapy of malignant diseases.

PMID- 15161675
TI  - Imatinib for small cell lung cancer, aiming for a target in vivo.

PMID- 15161674
TI  - Extracellular nucleotides are potent stimulators of human hematopoietic stem
      cells in vitro and in vivo.
AB  - Although extracellular nucleotides support a wide range of biologic responses of
      mature blood cells, little is known about their effect on blood cell progenitor
      cells. In this study, we assessed whether receptors for extracellular nucleotides
      (P2 receptors [P2Rs]) are expressed on human hematopoietic stem cells (HSCs), and
      whether activation by their natural ligands, adenosine triphosphate (ATP) and
      uridine triphosphate (UTP), induces HSC proliferation in vitro and in vivo. Our
      results demonstrated that CD34(+) HSCs express functional P2XRs and P2YRs of
      several subtypes. Furthermore, stimulation of CD34(+) cells with extracellular
      nucleotides caused a fast release of Ca(2+) from intracellular stores and an
      increase in ion fluxes across the plasma membrane. Functionally, ATP and, to a
      higher extent, UTP acted as potent early acting growth factors for HSCs, in
      vitro, because they strongly enhanced the stimulatory activity of several
      cytokines on clonogenic CD34(+) and lineage-negative CD34(-) progenitors and
      expanded more primitive CD34(+)-derived long-term culture-initiating cells.
      Furthermore, xenogenic transplantation studies showed that short-term
      preincubation with UTP significantly expanded the number of marrow-repopulating
      HSCs in nonobese diabetic/severe combined immunodeficiency mice. Our data suggest
      that extracellular nucleotides may provide a novel and powerful tool to modulate
      HSC functions.

PMID- 15161676
TI  - Gene expression profiling in non-small cell lung cancer: from molecular
      mechanisms to clinical application.
AB  - Non-small cell lung cancer (NSCLC) is the most common cause of premature death
      from malignant disease in western countries. A better understanding of the
      molecular mechanisms underlying NSCLC etiology, pathogenesis, and therapeutics
      will lead to improved clinical outcomes. Recent technological advances in gene
      expression profiling (in particular, with cDNA and oligonucleotide microarrays)
      allow the simultaneous analysis of the expression of thousands of genes. In this
      review, the technology of global gene expression profiling is discussed, and the
      progress made thus far with it in NSCLC is reviewed. A new molecular
      classification of NSCLC has been developed, which has provided important insights
      into etiology and pathogenesis. Other studies have found potential biomarkers for
      NSCLC that may be of use in diagnosis, screening, and assessing the effectiveness
      of therapy. Finally, advances have been made in the understanding of the
      molecular mechanisms of NSCLC progression and the molecular mechanisms of action
      of currently used cytotoxic drugs. This may facilitate the improvement of current
      therapeutics and the identification of novel targets. Taken together, these
      advances hold the promise of an improved understanding of the molecular biology
      of NSCLC and its treatment, which in turn will lead to improved outcomes for this
      deadly disease.

PMID- 15161677
TI  - Evidence-based use of neoadjuvant taxane in operable and inoperable breast
      cancer.
AB  - Neoadjuvant chemotherapy (NC) is standard therapy for patients with locally
      advanced breast cancer and is increasingly used for early-stage operable disease.
      The aim of NC is a pathological complete response (pCR) in the breast and
      axillary lymph nodes, which is the best predictor of improved outcome and
      prolonged survival. The taxanes docetaxel and paclitaxel are potent agents in
      breast cancer management, with promising single-agent activity and acceptable
      tolerability in the neoadjuvant setting. In this review of the taxanes as NC for
      operable and inoperable breast cancer, we include all fully published Phase II
      III studies enrolling > or =30 patients. Current evidence suggests that the
      sequential administration of taxane- and anthracycline-based therapy may be
      superior to concomitant administration. Indeed, until the recent Phase III
      Aberdeen study (n = 162), it was uncertain whether NC could prolong survival. In
      this study, sequential docetaxel after anthracycline-based NC significantly
      enhanced the clinical response rate and pathological complete response, and
      yielded a significant 3-year survival advantage, versus anthracycline-based NC
      alone. Recently, the Phase III National Surgical Adjuvant Breast and Bowel
      Project (NSABP) trial B27 trial (n = 2411) showed that sequential docetaxel after
      doxorubicin-cyclophosphamide significantly increased both clinical and
      pathological response rates for operable breast cancer, with the benefit evident
      in both estrogen receptor-positive and estrogen receptor-negative patients. This
      apparent superiority of a sequential anthracycline-taxane regimen is limited to
      docetaxel, with no similar Phase III trials of paclitaxel versus a non-taxane
      based comparator having been conducted to date. In conclusion, current evidence
      supports the inclusion of a taxane in NC schedules for patients with large and
      locally advanced breast cancer.

PMID- 15161678
TI  - Chemoresistance: impact of nuclear factor (NF)-kappaB inhibition by small
      interfering RNA. Commentary re J. Guo et al., Enhanced chemosensitivity to
      irinotecan by RNA interference-mediated down-regulation of the NF-kappaB p65
      subunit. Clin Cancer Res 2004;10:3333-3341.

PMID- 15161679
TI  - A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride
      (LY335979), administered intravenously in combination with doxorubicin in
      patients with advanced malignancy.
AB  - PURPOSE: Our intention was to (a) to investigate the safety and tolerability of a
      potent P-glycoprotein modulator, zosuquidar trihydrochloride (LY335979), when
      administered i.v. alone or in combination with doxorubicin, (b) to determine the
      pharmacokinetics of zosuquidar and correlate exposure to inhibition of P
      glycoprotein function in a surrogate assay, and (c) to compare the
      pharmacokinetics of doxorubicin in the presence and absence of zosuquidar.
      PATIENTS AND METHODS: Patients with advanced malignancies who provided written
      informed consent received zosuquidar and doxorubicin administered separately
      during the first cycle of therapy and then concurrently in subsequent cycles.
      Zosuquidar was given i.v. over 48 h in a cohort-dose escalation manner until the
      occurrence of dose-limiting toxicity or protocol specified maximum exposure.
      Doxorubicin doses of 45, 60, 75 mg/m(2) were administered during the course of
      the trial. RESULTS: Dose escalation proceeded through 9 cohorts with a total of
      40 patients. The maximal doses administered were 640 mg/m(2) of zosuquidar and 75
      mg/m(2) of doxorubicin. No dose-limiting toxicity of zosuquidar was observed.
      Pharmacokinetic analysis revealed that, in the presence of zosuquidar at doses
      that exceeded 500 mg, there was a modest decrease in clearance (17-22%) and
      modest increase in area under the curve (15-25%) of doxorubicin. This change was
      associated with an enhanced leukopenia and thrombocytopenia but was without
      demonstrable clinical significance. The higher doses of zosuquidar were
      associated with maximal P-glycoprotein inhibition in natural killer cells.
      CONCLUSION: Zosuquidar can be safely coadministered with doxorubicin using a 48 h
      i.v. dosing schedule.

PMID- 15161680
TI  - Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune
      responses in colorectal carcinoma patients vaccinated with recombinant CEA and
      granulocyte/macrophage colony-stimulating factor.
AB  - PURPOSE: Previous studies have indicated that carcinoembryonic antigen (CEA)
      might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The
      aim of the present study was to analyze the immunological and clinical effects of
      vaccination with CEA together with the adjuvant granulocyte/macrophage colony
      stimulating factor (GM-CSF). EXPERIMENTAL DESIGN: Twenty-four resected CRC
      patients without macroscopic disease were immunized seven times with recombinant
      CEA at four different dose levels over a 12-month period. Half of the patients
      received GM-CSF (80 microg/day for 4 consecutive days) at each immunization.
      Patients were monitored immunologically for 36 months and clinically for 76
      months. T-cell response was evaluated by a [(3)H]thymidine incorporation assay,
      and IgG response was determined by ELISA. RESULTS: Minor local side effects were
      common. All 12 patients (100%) in the GM-CSF group developed a CEA-specific T
      cell as well as an IgG response. The corresponding figures in the CEA alone group
      were 9 of 12 (75%) and 8 of 12 (66%), respectively. GM-CSF significantly
      augmented the amplitude of the T-cell response and the IgG titers. No dose
      response relationship was noted. The immune responses at 12 months persisted 24
      months after the last vaccination. Anti-CEA IgG titers were associated with
      increased survival (P < 0.05), whereas standard prognostic factors had no
      relationship, with the exception of serum CEA value. CONCLUSIONS: Vaccination
      with recombinant CEA and GM-CSF appears to be a nontoxic regimen inducing potent
      and durable antigen-specific IgG and T-cell response. The results of this study
      justify more extensive trials with recombinant CEA protein for immunotherapy of
      CRC.

PMID- 15161681
TI  - Gene expression in gastrointestinal stromal tumors is distinguished by KIT
      genotype and anatomic site.
AB  - PURPOSE: Gastrointestinal stromal tumors (GISTs) are specific KIT expressing and
      KIT-signaling driven mesenchymal tumors of the human digestive tract, many of
      which have KIT-activating mutations. Previous studies have found a relatively
      homogeneous gene expression profile in GIST, as compared with other histological
      types of sarcomas. Transcriptional heterogeneity within clinically or molecularly
      defined subsets of GISTs has not been previously reported. We tested the
      hypothesis that the gene expression profile in GISTs might be related to KIT
      genotype and possibly to other clinicopathological factors. EXPERIMENTAL DESIGN:
      An HG-U133A Affymetrix chip (22,000 genes) platform was used to determine the
      variability of gene expression in 28 KIT-expressing GIST samples from 24
      patients. A control group of six intra-abdominal leiomyosarcomas was also
      included for comparison. Statistical analyses (t tests) were performed to
      identify discriminatory gene lists among various GIST subgroups. The levels of
      expression of various GIST subsets were also linked to a modified version of the
      growth factor/KIT signaling pathway to analyze differences at various steps in
      signal transduction. RESULTS: Genes involved in KIT signaling were differentially
      expressed among wild-type and mutant GISTs. High gene expression of potential
      drug targets, such as VEGF, MCSF, and BCL2 in the wild-type group, and Mesothelin
      in exon 9 GISTs were found. There was a striking difference in gene expression
      between stomach and small bowel GISTs. This finding was validated in four
      separate tumors, two gastric and two intestinal, from a patient with familial
      GIST with a germ-line KIT W557R substitution. CONCLUSIONS: GISTs have
      heterogeneous gene expression depending on KIT genotype and tumor location, which
      is seen at both the genomic level and the KIT signaling pathway in particular.
      These findings may explain their variable clinical behavior and response to
      therapy.

PMID- 15161682
TI  - Selection of potential markers for epithelial ovarian cancer with gene expression
      arrays and recursive descent partition analysis.
AB  - PURPOSE: Advanced-stage epithelial ovarian cancer has a poor prognosis with long
      term survival in less than 30% of patients. When the disease is detected in stage
      I, more than 90% of patients can be cured by conventional therapy. Screening for
      early-stage disease with individual serum tumor markers, such as CA125, is
      limited by the fact that no single marker is up-regulated and shed in adequate
      amounts by all ovarian cancers. Consequently, use of multiple markers in
      combination might detect a larger fraction of early-stage ovarian cancers.
      EXPERIMENTAL DESIGN: To identify potential candidates for novel markers, we have
      used Affymetrix human genome arrays (U95 series) to analyze differences in gene
      expression of 41,441 known genes and expressed sequence tags between five pools
      of normal ovarian surface epithelial cells (OSE) and 42 epithelial ovarian
      cancers of different stages, grades, and histotypes. Recursive descent partition
      analysis (RDPA) was performed with 102 probe sets representing 86 genes that were
      up-regulated at least 3-fold in epithelial ovarian cancers when compared with
      normal OSE. In addition, a panel of 11 genes known to encode potential tumor
      markers [mucin 1, transmembrane (MUC1), mucin 16 (CA125), mesothelin, WAP four
      disulfide core domain 2 (HE4), kallikrein 6, kallikrein 10, matrix
      metalloproteinase 2, prostasin, osteopontin, tetranectin, and inhibin] were
      similarly analyzed. RESULTS: The 3-fold up-regulated genes were examined and four
      genes [Notch homologue 3 (NOTCH3), E2F transcription factor 3 (E2F3), GTPase
      activating protein (RACGAP1), and hematological and neurological expressed 1
      (HN1)] distinguished all tumor samples from normal OSE. The 3-fold up-regulated
      genes were analyzed using RDPA, and the combination of elevated claudin 3 (CLDN3)
      and elevated vascular endothelial growth factor (VEGF) distinguished the cancers
      from normal OSE. The 11 known markers were analyzed using RDPA, and a combination
      of HE4, CA125, and MUC1 expression could distinguish tumor from normal specimens.
      Expression at the mRNA level in the candidate markers was examined via
      semiquantitative reverse transcription-PCR and was found to correlate well with
      the array data. Immunohistochemistry was performed to identify expression of the
      genes at the protein level in 158 ovarian cancers of different histotypes. A
      combination of CLDN3, CA125, and MUC1 stained 157 (99.4%) of 158 cancers, and all
      of the tumors were detected with a combination of CLDN3, CA125, MUC1, and VEGF.
      CONCLUSIONS: Our data are consistent with the possibility that a limited number
      of markers in combination might identify >99% of epithelial ovarian cancers
      despite the heterogeneity of the disease.

PMID- 15161683
TI  - Disease-stage variance in functional CD4(+) T-cell responses against novel pan
      human leukocyte antigen-D region presented human papillomavirus-16 E7 epitopes.
AB  - Given the anticipated clinical importance of helper and regulatory CD4(+) T cells
      reactive against human papillomavirus-16 E7 in the cervical carcinoma setting, we
      performed this study to identify novel E7-derived T helper (Th) epitopes and to
      characterize functional anti-E7 Th responses in normal donors and patients with
      cervical intraepithelial neoplasia I-III or cervical cancer. Candidate pan-HLA-DR
      (D region) binding peptides were identified and synthesized based on results
      obtained using a predictive computer algorithm, then applied in short-term in
      vitro T-cell sensitization assays. Using IFN-gamma/IL-5 (interleukin 5) enzyme
      linked immunospot assays as readouts for Th1-type and Th2-type CD4(+) T-cell
      responses, respectively, we identified three E7-derived T helper epitopes (E7(1
      12), E7(48-62), and E7(62-75)), two of which are novel. Normal donor CD4(+) T
      cells failed to react against these E7 peptides, whereas patients with
      premalignant cervical intraepithelial neoplasia I-III lesions displayed
      preferential Th1-type responses against all three E7 epitopes. Th1-type responses
      were still observed to the E7(48-62) but not to the E7(1-12) and E7(62-75)
      peptides in cancer patients, where these latter two epitopes evoked Th2-type
      responses. Notably all responders to the E7(1-12) and E7(62-75) peptides
      expressed the HLA-DR4 or -DR15 alleles, whereas all responders to the E7(48-62)
      peptide failed to express the HLA-DR4 allele. Our results are consistent with a
      model in which cervical cancer progression is linked to an undesirable Th1- to
      Th2-type shift in functional CD4(+) T cell responses to two novel E7-derived
      epitopes. These peptides may prove important in vaccines to promote and maintain
      protective Th1-type antihuman papillomavirus immunity and in the immune
      monitoring of treated patients harboring HPV-16(+) malignancies.

PMID- 15161684
TI  - p73 expression is associated with the cellular radiosensitivity in cervical
      cancer after radiotherapy.
AB  - Apoptosis is one of the causes of cell death in cervical cancer following
      radiotherapy. By studying the gene expression profile with cDNA apoptotic array,
      the p73 gene was found overexpressed in radiosensitive cervical cancers when
      compared with radioresistant ones. To investigate the role of the p73 gene in
      relation to clinical assessment of radiosensitivity in cervical cancer based on
      the findings of residual tumor cells in cervical biopsies after completion of
      radiotherapy, we studied the protein expression of p73 in 59 cervical cancers
      after radiotherapy and 68 normal cervices using immunohistochemistry. The
      expression of p73 was found to be significantly increased in cancer samples and,
      more importantly, in those samples sensitive to radiotherapy (P < 0.001). The
      overexpression of p73 actually predicted a better prognosis in cervical cancer
      patients (P < 0.001). To investigate the possible involvement of p73 downstream
      genes, the protein expressions of p21 and Bax were studied. The expression of
      p21, but not Bax, was found to be positively correlated with the expression of
      p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA
      methylation was also investigated in 103 cervical cancers and 124 normals.
      Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it
      was significantly associated with reduced or absent p73 expression (P < 0.001).
      Reactivation of p73 expression in two cervical cancer cell lines by demethylation
      treatment supported the role of methylation in the regulation of p73 expression.
      Our findings suggested that p73 expression was related to the radiosensitivity of
      cervical cancer cells and may play an important role in the regulation of
      cellular radiosensitivity.

PMID- 15161685
TI  - Telomere length abnormalities occur early in the initiation of epithelial
      carcinogenesis.
AB  - PURPOSE: Telomeres help maintain chromosomal integrity. Dysfunctional telomeres
      can cause genetic instability in vitro and an increased cancer incidence in
      telomerase knock out mouse models. We recently reported that telomere shortening
      was a prevalent alteration in human prostate, pancreas, and breast cancer
      precursor lesions. In the present study, we address whether the previous findings
      are broadly applicable to human epithelial cancer precursors in general.
      EXPERIMENTAL DESIGN: Surgical specimens of epithelial cancer precursor lesions
      from the urinary bladder, esophagus, large intestine, oral cavity, and uterine
      cervix were examined using a recently developed technique for direct in situ
      telomere length assessment in formalin-fixed human tissue specimens. RESULTS:
      Widespread telomere length abnormalities were nearly universal (97.1% of cases)
      in the preinvasive stages of human epithelial carcinogenesis in all sites
      examined in this series, with telomere shortening the predominant abnormality
      (88.6% of cases). CONCLUSIONS: Telomere length abnormalities appear to be one of
      the earliest and most prevalent genetic alterations acquired in the multistep
      process of malignant transformation. These findings support a model whereby
      telomere dysfunction induces chromosomal instability as an initiating event in
      many, perhaps most, human epithelial cancers. Together with previous findings
      from the prostate and pancreas, the percentage of intraepithelial neoplasia
      lesions showing telomere length abnormalities is 95.6%. The implications of these
      findings include the potential that telomere length assessment in situ may be a
      widely useful biomarker for monitoring disease prevention strategies and for
      improved early diagnosis.

PMID- 15161686
TI  - Vascular endothelial growth factor-trap suppresses tumorigenicity of multiple
      pancreatic cancer cell lines.
AB  - PURPOSE: Vascular endothelial growth factor A (VEGF-A) is a potent angiogenic
      agent that binds to two high affinity VEGF receptors (VEGFRs), a process
      facilitated by the low affinity neuropilin receptors. Although VEGF-A is
      overexpressed in pancreatic ductal adenocarcinoma, it is not known whether the in
      vivo growth of multiple pancreatic cancer cells can be efficiently blocked by
      VEGF-A sequestration. EXPERIMENTAL DESIGN: Four human pancreatic cancer cell
      lines were grown s.c. in athymic nude mice. One cell line also was used to
      generate an orthotopic model of metastatic pancreatic cancer. The consequences of
      VEGF-A sequestration on tumor growth and metastasis were examined by injecting
      the mice with a soluble VEGFR chimer (VEGF-Trap) that binds VEGF-A with high
      affinity. RESULTS: VEGF-Trap, initiated 2 days after tumor cell inoculation,
      suppressed the s.c. growth of four pancreatic cancer cell lines and markedly
      decreased tumor microvessel density. Analysis of RNA from tumors generated with
      T3M4 cells revealed that VEGF-Trap decreased the expression of VEGFR-1 and
      neuropilin-1 and -2. VEGF-Trap, initiated 3 weeks after tumor implantation, also
      attenuated intrapancreatic tumor growth and metastasis in an orthotopic model
      using PANC-1 cells. CONCLUSIONS: VEGF-Trap is a potent suppressor of pancreatic
      tumor growth and metastasis and also may act to attenuate neuropilin-1 and -2 and
      VEGFR-1 expression. Therefore, VEGF-Trap may represent an exceedingly useful
      therapeutic modality for pancreatic ductal adenocarcinoma.

PMID- 15161687
TI  - Enhanced chemosensitivity to irinotecan by RNA interference-mediated down
      regulation of the nuclear factor-kappaB p65 subunit.
AB  - In preclinical tumor models, inhibition of nuclear factor-kappaB (NF-kappaB) has
      been associated with increased sensitivity to chemotherapeutic agents such as
      irinotecan (CPT-11). This is based on the fact that a variety of chemotherapy
      agents such as CPT-11 activate NF-kappaB to result in the expression of genes
      such as c-IAP1 and c-IAP2 that might be responsible for the inhibition of
      chemotherapy-induced apoptosis. In this study, RNA interference [small
      interfering RNA (siRNA)] was used to down-regulate the NF-kappaB p65 subunit in
      the HCT116 colon cancer cell line, and its role, in the presence and absence of
      CPT-11, was assessed on cell growth and apoptosis. Reduction of endogenous p65 by
      siRNA treatment significantly impaired CPT-11-mediated NF-kappaB activation,
      enhanced apoptosis, and reduced colony formation in soft agar. Furthermore, the
      in vivo administration of p65 siRNA reduced HCT116 tumor formation in xenograft
      models in the presence but not the absence of CPT-11 administration. These data
      indicate that the administration of siRNA directed against the p65 subunit of NF
      kappaB can effectively enhance in vitro and in vivo sensitivity to
      chemotherapeutic agents.

PMID- 15161688
TI  - Hypoxia and hypoxia-inducible factor-1 target genes in central nervous system
      radiation injury: a role for vascular endothelial growth factor.
AB  - PURPOSE: Microvascular permeability changes and loss of blood-brain barrier
      integrity are important features of central nervous system (CNS) radiation
      injury. Expression of vascular endothelial growth factor (VEGF), an important
      determinant of microvascular permeability, was examined to assess its role in CNS
      radiation damage. Because hypoxia mediates VEGF up-regulation through hypoxia
      inducible factor-1alpha (HIF1alpha) induction, we studied the relationships of
      hypoxia, HIF1alpha expression, and expression of VEGF in this damage pathway.
      EXPERIMENTAL DESIGN: Expression of HIF1alpha, VEGF, and another hypoxia
      responsive gene, glucose transporter-1, was assessed in the irradiated rat spinal
      cord using immunohistochemistry and in situ hybridization. Hypoxic areas were
      identified using the nitroimidazole 2-(2-nitro-1H-imidazole-L-yl)-N-(2,2,3,3,3,
      pentafluoropropyl) acetamide. To determine the causal importance of VEGF
      expression in radiation myelopathy, we studied the response of transgenic mice
      with greater (VEGF-A(hi/+)), reduced (VEGF-A(lo/+)), and wild-type VEGF activity
      to thoracolumbar irradiation. RESULTS: In rat spinal cord, the number of cells
      expressing HIF1alpha and VEGF increased rapidly from 16 to 20 weeks after
      radiation, before white matter necrosis and forelimb paralysis. A steep dose
      response was observed in expression of HIF1alpha and VEGF. HIF1alpha and VEGF
      expressing cells were identified as astrocytes. Hypoxia was present in regions
      where up-regulation of VEGF and glucose transporter-1 and increased permeability
      was observed. VEGF-A(lo/+) mice had a longer latency to development of hindlimb
      weakness and paralysis compared with wild-type or VEGF-A(hi/+) mice. CONCLUSIONS:
      VEGF expression appears to play an important role in CNS radiation injury. This
      focuses attention on VEGF and other genes induced in response to hypoxia as
      targets for therapy to reduce or prevent CNS radiation damage.

PMID- 15161689
TI  - Differential up-regulation of cytosolic and membrane-bound heat shock protein 70
      in tumor cells by anti-inflammatory drugs.
AB  - PURPOSE: Modulation of the heat shock protein (HSP) response affects sensitivity
      to therapeutic agents in cancer. Here, drugs with anti-inflammatory potential
      (cyclooxygenase 1/2 inhibitors) and peroxidase proliferator-activated receptor
      gamma agonists were analyzed for their capacity to affect Hsp70 expression in
      human cancer cells with a divergent Hsp70 membrane expression pattern.
      EXPERIMENTAL DESIGN: In dose kinetics, the nonlethal concentration of acetyl
      salicyl acid, celecoxib, rofecoxib, and the insulin-sensitizer pioglitazone was
      identified for the human adenocarcinoma cell line CX-. With the exception of CLX,
      which was diluted in DMSO, all reagents were dissolved in water. After treatment
      with the different compounds at nontoxic concentrations for 6 h, followed by a 1
      h recovery period, the cytosolic Hsp70 levels were measured in CX-2 and CX- tumor
      cells by Western blot analysis. Fold increase was calculated in relation to the
      housekeeping protein tubulin. Membrane-bound Hsp70 was analyzed by flow cytometry
      using a FITC-labeled Hsp70-specific monoclonal antibody. Untreated cells and
      cells incubated with equivalent amounts of the diluting agents served as
      controls. The immunological function was tested in granzyme B apoptosis assays,
      standard (51)Cr release assays, and antibody blocking studies. RESULTS: Compared
      with aqua dest, the cytoplasmic amount of Hsp70 was equally enhanced in CX-2 and
      CX- cells by all compounds. An increase in membrane-bound Hsp70, detected
      selectively in CX- cells, corresponded to an enhanced sensitivity to granzyme B-
      and natural killer cell-mediated kill that was blockable by using a Hsp70
      specific antibody. CONCLUSIONS: Although increase in cytosolic Hsp70 levels
      conferred resistance to further stress, membrane-bound Hsp70 rendered tumor cells
      more sensitive to the immunological attack mediated by granzyme B and natural
      killer cells. Our data provide a biological rational for combining anti
      inflammatory drugs with immunotherapy in cancer therapy.

PMID- 15161690
TI  - A randomized Phase II trial of the antiangiogenic agent SU5416 in hormone
      refractory prostate cancer.
AB  - PURPOSE: To assess the activity of the antiangiogenic agent and VEGFR2 inhibitor
      SU5416 in hormone-refractory prostate cancer. PATIENTS AND METHODS: Thirty-six
      chemotherapy naive patients were randomized to treatment with SU5416 (145
      mg/m(2)) and dexamethasone premedication or dexamethasone alone. Patients in the
      control arm could cross over to experimental therapy after progression. Prostate
      specific antigen (PSA) was measured every 2 weeks, and radiological evaluation
      was performed every 8 weeks. In vitro assessment of SU5416 on PSA secretion was
      assessed in the LNCaP cell line. Baseline serum basic fibroblast growth factor
      and plasma vascular endothelial growth factor (VEGF) were explored as prognostic
      factors. RESULTS: VEGF receptor-2 expression is detectable in prostate cancer
      cell lines, and SU5416 inhibited in vitro PSA secretion. No effect of SU5416 on
      PSA secretion or time to progression is detectable in patients. VEGF and basic
      fibroblast growth factor were not prognostic. Headache and fatigue were the most
      common SU5416 toxicities, but hyperglycemia, hyponatremia, lymphopenia,
      infection, and adrenal suppression, all attributable to steroids and the required
      central line, were common. CONCLUSION: No disease modifying effects of SU5416
      were detectable in this small study. Modest toxicity, an inconvenient
      administration schedule, and availability of other VEGFR-targeted agents support
      the decision to halt further evaluation of SU5416 in prostate cancer.

PMID- 15161691
TI  - Phase I study of bortezomib in refractory or relapsed acute leukemias.
AB  - Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented
      antitumor activity in multiple myeloma and other lymphoid malignancies. We
      performed a Phase I study to investigate the maximum tolerated dose and dose
      limiting toxicity of bortezomib in patients with acute leukemias refractory to or
      relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3),
      1.25 (n = 7), or 1.5 (n = 5) mg/m(2) bortezomib administered twice weekly for 4
      weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n =
      2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5
      mg/m(2) bortezomib. Proteasome inhibition was dose dependent and reached 68% at
      1.5 mg/m(2) bortezomib. Peak inhibition was observed 1 h after treatment and
      returned to near baseline levels by 72 h after treatment. Incubation of blast
      cells with bortezomib in vitro showed induction of apoptosis in three of five
      patients investigated. We conclude that the maximum tolerated dose of bortezomib
      in patients with acute leukemia is 1.25 mg/m(2), using a twice-weekly for 4 weeks
      every 6 weeks schedule. The in vitro evidence of antileukemia and transient
      hematological improvements observed in some patients warrants further
      investigation of bortezomib in acute leukemias, probably in combination with
      other agents.

PMID- 15161692
TI  - Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in
      advanced solid tumor patients.
AB  - PURPOSE: We performed a Phase I and pharmacokinetic study to determine the
      maximum tolerated dose of irofulven (6-hydroxymethylacylfulvene; MGI-114, MGI
      PHARMA, Inc.), administered in intermittent weekly schedules in patients with
      advanced solid tumors. EXPERIMENTAL DESIGN: Three schedules were tested: A, days
      1, 8, and 15 every 4 weeks; B, days 1 and 8 every 3 weeks; C, days 1 and 15 every
      4 weeks. Drugs were administered as 5- and 30-min (schedules B and C) infusions.
      Dose levels of 10, 12, and 14 mg/m(2)/week were explored. RESULTS: Ninety-nine
      patients received 256 cycles. Fifteen of 74 patients evaluable for maximum
      tolerated dose experienced 16 dose-limiting toxicities (5 of 17 patients on
      schedule A, 2 of 25 on schedule B, and 8 of 32 on schedule C), principally
      treatment delay for thrombocytopenia. Schedule A was considered unsuitable
      because of frequent thrombocytopenia and treatment discontinuations. Twenty-three
      percent of the overall population (22 patients with grade 1-2, and 1 patient with
      grade 3), including 37% of patients on dose level 3, experienced unexpected dose
      limiting visual toxicity, which included color perception and visual field
      alterations linked to retinal cone cell toxicity; the visual toxicity had an
      early onset, was mostly reversible, and was related to higher dose per infusion.
      Safety profiles were similar for 5- and 30-min infusions. The relationships
      between dose and area under the plasma concentration-time curve and maximum
      plasma concentration were linear for both 5- and 30-min infusions in the 78
      patients evaluated for pharmacokinetics. The area under the plasma concentration
      time curve and clearance were comparable between infusion durations. Responses
      included one complete (ovarian), one partial (renal), and seven disease
      stabilizations lasting >4 months. CONCLUSIONS: We recommend doses of 18
      mg/m(2)/infusion for schedule B and 24 mg/m(2)/infusion for schedule C, limited
      to 0.55 mg/kg and a total dose of 50 mg/infusion, administered over 30-min.

PMID- 15161694
TI  - Analysis of aberrant DNA methylation and human papillomavirus DNA in
      cervicovaginal specimens to detect invasive cervical cancer and its precursors.
AB  - PURPOSE: Cancer of the uterine cervix is an important cause of death in women
      worldwide. Pap smears as a tool for screening decreased the incidence and
      mortality of cervical cancer dramatically. This proof of principle study aimed to
      develop a potential tool for cervical screening using a test that can be applied
      by patients without visiting a physician and to increase the coverage rate,
      especially of the high-risk population with low socioeconomic status.
      EXPERIMENTAL DESIGN: Human papillomavirus (HPV) DNA testing and methylation
      analysis of DNA obtained from cervicovaginal specimens of 13, 31, and 11 patients
      with no dysplasia/low-grade squamous intraepithelial lesion (SIL), high-grade
      SIL, and invasive cervical cancer, respectively, collected on a tampon, was
      performed using PCR-based methods to detect invasive cervical cancer and study
      whether these changes are already present in the precursor lesions. RESULTS: High
      risk HPV DNA was present in 68 and 82% of patients with high-grade SIL and
      invasive cervical cancer. DNA methylation of the 11 genes tested increased with
      severity of the cervical lesion. Unsupervised hierarchical cluster analysis using
      solely information on DNA methylation of the 11 genes was able to predict the
      presence of invasive cervical cancers: one of the two clusters formed contained 9
      of 11 invasive cervical cancers, as well as two high-grade SILs. CONCLUSIONS: HPV
      DNA and DNA methylation analyzed in cervicovaginal specimens are able to predict
      invasive cervical cancers. To detect all high-grade SILs when applying this test,
      genes that become methylated earlier throughout cervical carcinogenesis have to
      be defined.

PMID- 15161693
TI  - A Phase I and pharmacological study of the platinum polymer AP5280 given as an
      intravenous infusion once every 3 weeks in patients with solid tumors.
AB  - PURPOSE: This Phase I study was designed to determine the maximum tolerated dose,
      profile of adverse events, and dose-limiting toxicity of AP5280 in patients with
      solid tumors. Furthermore, the platinum (Pt) pharmacokinetics after AP5280
      administration and preliminary antitumor activity were evaluated. AP5280 is a Pt
      agent linked to the water-soluble, biocompatible copolymer N-(2
      hydroxypropyl)methacrylamide, which potentially increases Pt accumulation in
      tumors via the enhanced permeability and retention effect. In this way, it is
      anticipated that a higher activity of therapeutic Pt can be reached. The
      pharmaceutical product contains approximately 8.5% of Pt by weight and has a
      molecular weight of approximately 25,000. EXPERIMENTAL DESIGN: Adult patients
      with solid tumors received AP5280 as a 1-h i.v. infusion every 21 days.
      Pharmacokinetics of total and unbound Pt were determined during the first
      treatment course and before the start of each new cycle using noncompartmental
      pharmacokinetic analysis. Pt-DNA adduct concentrations in WBCs and, if available,
      in tumor tissue were quantified using a sensitive (32)P postlabeling assay.
      RESULTS: Twenty-nine patients were treated at eight dose levels (90-4500 mg
      Pt/m(2)). The dose-limiting toxicity was Common Toxicity Criteria grade 3
      vomiting and was experienced at 4500 mg Pt/m(2) in two of six patients. The
      maximum tolerated dose on this schedule was therefore 4500 mg Pt/m(2), and the
      recommended dose for a Phase II study is 3300 mg Pt/m(2). Renal toxicity and
      myelosuppression, toxicities typically observed with cisplatin and carboplatin,
      were minimal for AP5280. The area under the curve of total Pt increased with
      increasing AP5280 dose. Plasma clearance of total Pt was 644 +/- 266 ml/h, and
      the terminal half-life was 116 +/- 46.2 h. After AP5280 administration, Pt
      guanine-guanine DNA adduct concentrations in WBCs ranged from 70 to 1848
      amol/microg DNA, concentrations that were substantially lower than concentrations
      measured after administration of therapeutic doses of cisplatin. CONCLUSIONS:
      AP5280 can be administered safely as a 1-h i.v. infusion at a dose of 3300 mg
      Pt/m(2) once every 3 weeks and produces prolonged plasma exposure compared with
      any of the free Pt-containing drugs. However, it remains to be determined whether
      AP5280 can actually increase Pt delivery to the DNA of tumor cells in man as has
      been shown in experimental models.

PMID- 15161695
TI  - Cellular immunity in breast cancer patients completing taxane treatment.
AB  - PURPOSE: A field study of postchemotherapy immune functioning relative to the use
      of taxanes is reported. Immune responses in breast cancer patients were analyzed
      as a function of whether patients received taxane as part of their adjuvant
      chemotherapy. EXPERIMENTAL DESIGN: Immune levels of 227 stage II/III breast
      cancer patients were measured immediately after surgery prior to chemotherapy and
      again 12 months later when all chemotherapies had been completed. T-cell
      blastogenesis and natural killer (NK) cell lysis levels of patients receiving
      taxanes (n = 55) were compared with levels of patients not receiving taxanes (n =
      172). RESULTS: Regression analyses were conducted. The administration of taxane
      as part of combination chemotherapy predicted increased T-cell blastogenesis and
      NK cell cytotoxicity after the conclusion of all chemotherapies. For the Taxane
      group, average phytohemagglutinin-induced blastogenesis was 37% higher and NK
      cell cytotoxicity was 39% higher than the values for the No-Taxane group.
      CONCLUSIONS: Data from group comparisons with appropriate controls in a sizable
      clinical sample contravene traditional wisdom that taxanes suppress patients'
      immune cell functions. Problems in generalizing direct-contact laboratory models
      to the field of cancer treatment are highlighted.

PMID- 15161696
TI  - Identifying superficial, muscle-invasive, and metastasizing transitional cell
      carcinoma of the bladder: use of cDNA array analysis of gene expression profiles.
AB  - PURPOSE: Expression profiling by DNA microarray technology permits the
      identification of genes underlying clinical heterogeneity of bladder cancer and
      which might contribute to disease progression, thereby improving assessment of
      treatment and prediction of patient outcome. EXPERIMENTAL DESIGN: Invasive (20)
      and superficial (22) human bladder tumors from 34 patients with known outcome
      regarding disease recurrence and progression were analyzed by filter-based cDNA
      arrays (Atlas Human Cancer 1.2; BD Biosciences Clontech) containing 1185 genes.
      For 9 genes, array data were confirmed using real-time reverse transcription-PCR.
      Additionally, Atlas array data were validated using Affymetrix GeneChip
      oligonucleotide arrays with 22,283 human gene fragments and expressed sequence
      tags sequences in a subset of three superficial and six invasive bladder tumors.
      RESULTS: A two-way clustering algorithm using different subsets of gene
      expression data, including a subset of 41 genes validated by the oligonucleotide
      array (Affymetrix), classified tumor samples according to clinical outcome as
      superficial, invasive, or metastasizing. Furthermore, (a) a clonal origin of
      superficial tumors, (b) highly similar gene expression patterns in different
      areas of invasive tumors, and (c) an invasive-like pattern was observed in
      bladder mucosas derived from patients with locally advanced disease. Several gene
      clusters that characterized invasive or superficial tumors were identified. In
      superficial bladder tumors, increased mRNA levels of genes encoding transcription
      factors, molecules involved in protein synthesis and metabolism, and some
      proteins involved into cell cycle progression and differentiation were observed,
      whereas transcripts for immune, extracellular matrix, adhesion, peritumoral
      stroma and muscle tissue components, proliferation, and cell cycle controllers
      were up-regulated in invasive tumors. CONCLUSIONS: Gene expression profiling of
      human bladder cancers provides insight into the biology of bladder cancer
      progression and identifies patients with distinct clinical phenotypes.

PMID- 15161697
TI  - Expression of extracellular matrix metalloproteases inducer on micrometastatic
      and primary mammary carcinoma cells.
AB  - PURPOSE: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated
      member of the immunoglobulin superfamily known to stimulate the production of
      matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral
      fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor
      progression in human breast cancer. EXPERIMENTAL DESIGN: An immunohistochemical
      study using high-density tissue microarrays (n = 2222 breast cancer samples) and
      EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results
      were statistically correlated with various clinicopathological parameters. To
      analyze the putative association between EMMPRIN expression and bone marrow (BM)
      micrometastasis, an additional set of 55 breast tumors from patients with or
      without micrometastatic cells as determined with anti-cytokeratin antibody A45
      B/B3 were included in our study. Cytokeratin-positive cells in BM were costained
      with EMMPRIN-specific antibody 1G6.2. RESULTS: Positive EMMPRIN staining
      correlated significantly with various histopathological risk factors (higher
      tumor grade, increased tumor size, negative estrogen receptor status and
      progesterone receptor status, and higher mitotic index) as well as decreased
      tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50
      years (i.e., postmenopausal women), EMMPRIN expression was an independent
      prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95%
      confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor
      progression was also supported by the fact that it was expressed on approximately
      90% of micrometastatic cells in BM. CONCLUSIONS: EMMPRIN expression in primary
      tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial
      role of EMMPRIN in progression of human mammary carcinomas.

PMID- 15161698
TI  - Reduced lecithin: retinol acyltransferase expression correlates with increased
      pathologic tumor stage in bladder cancer.
AB  - PURPOSE: Retinoids, which include vitamin A (retinol; ROL) and its derivatives,
      have been investigated in the treatment of bladder cancer. We have shown that
      expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL
      to retinyl esters, is reduced in several human cancers. Here we evaluated
      expression of LRAT protein and mRNA in normal and malignant bladder tissue
      specimens from human patients. We also examined the effect of retinoids on LRAT
      expression in bladder cancer cell lines. EXPERIMENTAL DESIGN: We evaluated 49
      bladder cancer specimens for LRAT protein expression using immunohistochemistry
      with affinity-purified antibodies to human LRAT. LRAT mRNA expression was
      assessed using reverse transcription-PCR in bladder specimens from an additional
      16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA
      expression in five human bladder cancer cell lines. RESULTS: LRAT protein was
      detected throughout the nonneoplastic bladder epithelium in all of the specimens.
      In bladder tumors, LRAT protein expression was reduced compared with the
      nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial
      tumors versus 16 of 17 (94.1%) invasive tumors (P < 0.001). All of the non
      neoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression,
      compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P
      = 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA
      independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression
      was induced by retinoid treatment. CONCLUSIONS: We report a significant reduction
      in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse
      correlation of LRAT mRNA and protein expression with increasing tumor stage.
      These data suggest that loss of LRAT expression is associated with invasive
      bladder cancer.

PMID- 15161699
TI  - Genetic and epigenetic changes in p21 and p21B do not correlate with resistance
      to doxorubicin or mitomycin and 5-fluorouracil in locally advanced breast cancer.
AB  - PURPOSE: The cyclin-dependent kinase inhibitor p21 acts as a main executor of p53
      induced growth arrest. Recently, a second transcript, p21B, was found to code for
      a protein expressing proapoptotic activity. We investigated p21 and p21B for
      mutations and epigenetic silencing in locally advanced breast cancers treated
      with doxorubicin or 5-fluorouracil/mitomycin and correlated our findings with
      treatment response and TP53 status. EXPERIMENTAL DESIGN: We used reverse
      transcription-PCR to analyze p21/p21B mutation status in 73 breast cancer
      samples. The p21 promoter region was sequenced and analyzed for hypermethylations
      by methylation-specific PCR. In addition, a selection of patients were analyzed
      for mutations in the p21B promoter. RESULTS: The p21 gene was neither mutated nor
      silenced by promoter hypermethylation in any of the tumors examined. One patient
      harbored a novel p21 splice variant in addition to the wild-type transcript. We
      observed two base substitutions in the p21 transcript, C93A and G251A, each
      affecting six patients (8.2%). The G251A variant had not been reported
      previously. In 12 patients (16.4%), we observed a novel base substitution, T35C,
      in p21B. All three base substitutions were observed in lymphocyte DNA and
      therefore considered polymorphisms. The polymorphisms did not correlate with p21
      staining index, treatment response to doxorubicin or 5-fluorouracil/mitomycin, or
      TP53 status. CONCLUSIONS: Our findings do not suggest that genetic or epigenetic
      disturbances in p21 or p21B cause resistance to doxorubicin or mitomycin/5
      fluorouracil in breast cancer. Future studies should assess potential
      associations between these novel polymorphisms and breast cancer risk.

PMID- 15161700
TI  - Exon 15 BRAF mutations are uncommon in melanomas arising in nonsun-exposed sites.
AB  - PURPOSE: An activating point mutation of the BRAF oncogene has been identified in
      a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in
      melanomas arising from the mucosa of head and neck is unknown. EXPERIMENTAL
      DESIGN: We tested 17 malignant mucosal melanomas of the head and neck for the
      thymine (T)-->adenine (A) missense mutation at nucleotide 1796 in the BRAF gene
      using direct sequencing and a newly developed assay that uses a novel primer
      extension method (Mutector assay). We also tested 21 cutaneous melanomas,
      including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the
      vulvar skin. RESULTS: The 1796T-->A mutation was detected in only 1 (6%) of the
      sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in
      8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar
      melanomas. CONCLUSIONS: In contrast to cutaneous melanomas arising in sun-exposed
      sites, mucosal melanomas of the head and neck do not frequently harbor an
      activating mutation of BRAF. This finding additionally supports the view that the
      various subtypes of melanoma are not equivalent and that distinct genetic
      alterations may underlie well recognized differences in risk factors and
      behavioral patterns. Accordingly, patients with melanomas should not be
      collectively regarded as a uniform group as new strategies are developed that
      target specific genetic alterations.

PMID- 15161701
TI  - Pak-1 expression increases with progression of colorectal carcinomas to
      metastasis.
AB  - PURPOSE: The p21-activated kinase-1 (Pak-1) promotes cell motility and
      invasiveness. Pak-1 is activated by the Rac, Rho, and Cdc42 small GTPases in
      response to a variety of stimuli including ras and phosphatidylinositol 3'
      kinase/AKT pathway activation. Because Pak-1 plays a central role in regulating
      cell motility and invasiveness, we sought to determine whether Pak-1 may be
      involved in the malignant progression of colorectal carcinoma. EXPERIMENTAL
      DESIGN: Pak-1 expression was examined by immunohistochemistry in archived tissues
      from normal human colons, tubular and tubulovillous adenomas, invasive
      adenocarcinomas (stages I-III/IV), and lymph node metastases (184 total specimens
      from 38 patients). Specific cytoplasmic immunostaining was evaluated for overall
      intensity and uniformity to derive a combined histoscore (stain intensity x
      percentage of epithelium stained). RESULTS: Pak-1 expression was increased
      significantly with colorectal cancer progression from normal tissue to lymph node
      metastases (P < 0.0001). Furthermore, Pak-1 expression was increased
      significantly in adenomas, invasive carcinomas, and lymph node metastases
      compared with normal colon (P < 0.0001). Strikingly, Pak-1 expression was
      significantly higher in lymph node metastases than in invasive cancers, adenomas,
      or normal colon (P < 0.0001). Moreover, in patients with multiple lesions
      representing different stages of disease, Pak-1 expression was increased
      specifically in the most advanced lesions. CONCLUSIONS: This study demonstrates
      that Pak-1 expression is increased significantly with malignant progression of
      human colorectal carcinoma. These data, along with numerous functional studies
      demonstrating a central role for Pak-1 activity in tumor invasiveness and
      motility, implicate Pak-1 as an exciting target for therapy of colorectal
      carcinoma.

PMID- 15161702
TI  - Genomic profiling of viable and proliferative micrometastatic cells from early
      stage breast cancer patients.
AB  - PURPOSE: Metastases in distant organs are the major cause of death for cancer
      patients, and bone marrow is a prominent homing organ for early disseminated
      cancer cells. However, it remains still unclear which of these cells evolve into
      overt metastases. We therefore established a new approach based on the analysis
      of viable and proliferating cancer cells by single-cell comparative genomic
      hybridization. EXPERIMENTAL DESIGN: The bone marrow of early-stage breast tumor
      patients (pN(0)M(0)) was screened for tumor cells by immunostaining. By applying
      special short-term culturing, we selected for viable and proliferative tumor
      cells. The short-term culturing allowed us to evaluate the proliferative
      potential of micrometastatic cells, which we had previously shown to represent an
      independent prognostic marker. We assessed genomic changes in single disseminated
      cancer cells by single-cell comparative genomic hybridization. RESULTS: We found
      that these viable disseminated cancer cells already had a plethora of copy number
      changes in their genome. All of these cells showed chromosomal copy number
      changes with a substantial intercellular heterogeneity and differences to the
      matching primary tumors. CONCLUSIONS: The established experimental strategy might
      pave the way for the identification of metastatic stem cells in cancer patients.
      Our preliminary results support the new concept that early disseminated cancer
      cells evolve independently from their primary tumor.

PMID- 15161703
TI  - Ability to predict metastasis based on pathology findings and alterations in
      nuclear structure of normal-appearing and cancer peripheral zone epithelium in
      the prostate.
AB  - PURPOSE: Malignant transformation in the prostate produces significant
      alterations in glandular architecture (Gleason grade) and nuclear structure that
      provide valuable prognostic information. Normal-appearing nuclei (NN) adjacent to
      cancer may also have altered functions in response to malignancy. We studied NN
      adjacent to peripheral zone (PZ) prostate cancer (PCa), as well as the PZ cancer
      nuclei (CaN) using quantitative image cytometry. The nuclear structure
      information was combined with routine pathological findings to predict metastatic
      PCa progression and/or death. EXPERIMENTAL DESIGN: Tissue microarrays of normal
      appearing and cancer areas were prepared from 182 pathologist-selected paraffin
      blocks. Feulgen-stained CaN and NN were captured from the tissue microarrays
      using the AutoCyte Pathology Workstation. Multivariate logistic regression was
      used to calculate quantitative nuclear grade (QNG) solutions based on nuclear
      morphometric descriptors determined from NN and CaN. Multivariate logistic
      regression and Kaplan-Meier plots were also used to predict risk for distant
      metastasis and/or PCa-specific death using QNG solutions and routine pathology.
      RESULTS: The pathology model yielded an area under the receiver operator
      characteristic curve of 72.5%. The QNG-NN and QNG-CaN solutions yielded an area
      under the receiver operator characteristic curve of 81.6 and 79.9%, respectively,
      but used different sets of nuclear morphometric descriptors. Kaplan-Meier plots
      for the pathology variables, the QNG-NN and QNG-CaN solutions, were combined with
      pathology to defined three statistically significantly distinct risk groups for
      distant metastasis and/or death (P < 0.0001). CONCLUSIONS: Alterations in cancer
      or normal-appearing nuclei adjacent to peripheral zone cancer areas can predict
      PCa progression and/or death. The QNG-NN and QNG-CA solutions could be combined
      with pathology variables to improve the prediction of distant metastasis.

PMID- 15161704
TI  - Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer.
AB  - PURPOSE: CA125 is currently the only tumor marker to have a validated role in the
      postoperative monitoring of ovarian cancer. Osteopontin (OPN) is a putative
      plasma biomarker that was recently identified using high-throughput cDNA
      microarray technology. The purpose of this study was to test the hypothesis that
      OPN is a clinically useful adjunct to CA125 in detecting recurrent ovarian
      cancer. EXPERIMENTAL DESIGN: Thirty-eight ovarian cancer patients had a single
      pretreatment blood sample and 200 postoperative specimens were prospectively
      collected during chemotherapy and follow-up. OPN measurements were performed
      using an enzyme-linked immunoassay, and CA125 levels were concurrently obtained.
      Wilcoxon's signed rank-sum test was used to perform paired comparisons between
      pretreatment and postoperative OPN and CA125 measurements. Longitudinal mixed
      effects polynomial models were used to determine whether OPN and CA125 levels
      correlated with the development of recurrent ovarian cancer. RESULTS: The median
      pretreatment OPN level was 178 ng/ml (range, 12-3468) and the median CA125
      measurement was 812 units/ml (range, 12-81,500). There was a trend for OPN levels
      to decline after treatment was initiated (P = 0.07), but decreasing CA125
      measurements were more consistently observed (P = 0.0009). The quadratic
      functional trends of OPN and CA125 were each highly significant (P < 0.0001).
      Although inferior to CA125 in predicting clinical response to therapy, OPN rose
      earlier in 90% (95% confidence interval, 56-100%) of the patients developing
      recurrent disease (median lead time, 3 months). CONCLUSIONS: OPN may be a
      clinically useful adjunct to CA125 in detecting recurrent ovarian cancer.

PMID- 15161705
TI  - Rapid and sensitive p53 alteration analysis in biopsies from lung cancer patients
      using a functional assay and a universal oligonucleotide array: a prospective
      study.
AB  - PURPOSE: Molecular profiling of alterations associated with lung cancer holds the
      promise to define clinical parameters such as response to treatment or survival.
      Because <5% of small cell lung cancers and <30% of non-small cell lung cancers
      are surgically resectable, molecular analysis will perforce rely on routinely
      available clinical samples such as biopsies. Identifying tumor mutations in such
      samples will require a sensitive and robust technology to overcome signal from
      excess amounts of normal DNA. EXPERIMENTAL DESIGN: p53 mutation status was
      assessed from the DNA and RNA of biopsies collected prospectively from 83
      patients with lung cancer. Biopsies were obtained either by conventional
      bronchoscopy or computed tomography-guided percutaneous biopsy. Matched surgical
      specimens were available for 22 patients. Three assays were used: direct
      sequencing; a functional assay in yeast; and a newly developed PCR/ligase
      detection reaction/Universal DNA array assay. RESULTS: Using the functional
      assay, p53 mutation was found in 62% of biopsies and 64% of surgical specimens
      with a concordance of 80%. The sensitivity of the functional assay was determined
      to be 5%. Direct sequencing confirmed mutations in 92% of surgical specimens but
      in only 78% of biopsies. The DNA array confirmed 100% of mutations in both
      biopsies and surgical specimens. Using this newly developed DNA array, we
      demonstrate the feasibility of directly identifying p53 mutations in clinical
      samples containing <5% of tumor cells. CONCLUSIONS: The versatility and
      sensitivity of this new array assay should allow additional development of
      mutation profiling arrays that could be applied to biological samples with a low
      tumor cell content such as bronchial aspirates, bronchoalveolar lavage fluid, or
      serum.

PMID- 15161706
TI  - Determination of molecular marker expression can predict clinical outcome in
      colon carcinomas.
AB  - PURPOSE: Conventional staging procedures are often unable to precisely predict
      prognosis in colorectal cancer (CRC). In this study, we set out to investigate
      the possible role of molecular/structural indicators involved in cell cycle
      regulation (p27 and p53), apoptosis (p53 and p27), and tumor neoangiogenesis
      [p53, vascular endothelial growth factor (VEGF), and microvessel count] in
      predicting tumor behavior and clinical outcome in CRC patients EXPERIMENTAL
      DESIGN: Analysis of the above indicators was performed by immunohistochemistry on
      104 CRC patient samples and 25 normal colon mucosa specimens. RESULTS: Intense
      p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining
      and VEGF cytoplasmic accumulation <10%, and low microvessel count. In contrast,
      in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed in
      52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple
      regression analysis showed that molecular markers were strongly correlated. In
      patients treated with curative surgery, a significant relationship was seen
      between p27 down-regulation and Dukes' stage, nodal status, and the presence of
      distant metastases. VEGF overexpression correlated significantly with Dukes'
      stage, tumor (t) and metastasis (m) parameters, and left site. Stepwise
      regression selected p27, p53, VEGF, and Dukes' stage as the best combination of
      variables capable of predicting both disease-specific and disease-free survival.
      CONCLUSIONS: The investigated indicators may be useful for the prediction of
      outcome and recurrence rate in curatively treated CRC patients. In conjunction
      with clinical and pathological staging, they may provide a stronger indication of
      clinical outcome than staging alone and help better select therapeutic options in
      CRC patients.

PMID- 15161707
TI  - c-Kit expression in patients with uterine leiomyosarcomas: a potential
      alternative therapeutic treatment.
AB  - PURPOSE: Uterine leiomyosarcomas are rare tumors characterized by their
      resistance to chemotherapy and radiation treatment. Surgery is the primary method
      of treatment, but for patients with unresectable disease, alternate therapeutic
      options are clearly warranted. According to initial observations of c-KIT
      expression, correlation with a bad prognosis, and the successful therapeutic
      possibility of STI571 in gastrointestinal stromal tumors, the data have
      encouraged us to study c-KIT expression in these tumors. EXPERIMENTAL DESIGN: We
      analyzed the expression of c-KIT and genetic assessment of exon 11 of c-kit gene
      in 32 uterine leiomyosarcomas. RESULTS: In 17 cases (53.1%), we observed a c-KIT
      expression in tumor cells. Of the 17 patients with distinct c-KIT-positive
      immunoreactivity, eight had I or II stage disease and nine had III or IV stage
      disease. Molecular genetic analysis of exon 11, analyzed by direct DNA
      sequencing, was performed for all of the c-KIT-positive uterine leiomyosarcomas.
      No mutations were found. CONCLUSION: The conventional chemotherapy in
      leiomyosarcomas appears to be ineffective for patients with metastatic or
      unresectable disease, and the management of these patients poses a special
      problem. In these women, new therapeutic strategies are warranted. The treatment
      with STI571 in leiomyosarcoma patients might be hypothesized, because uterine
      leiomyosarcomas also express c-KIT.

PMID- 15161708
TI  - Expression pattern of the novel gene EG-1 in cancer.
AB  - PURPOSE: We recently discovered a novel gene responsive to tumor-conditioned
      media: endothelial-derived gene 1 (EG-1). Its transcript has been shown to be
      present in epithelial cells, as well as in endothelial cells. In this study, we
      examined the levels of EG-1 protein expression in breast, colon, prostate, and
      lung cancers, which constitute the four most common solid malignancies in the
      United States. EXPERIMENTAL DESIGN: Polyclonal antibodies were generated that
      recognize the EG-1 peptide. These antibodies were used in immunoblot analysis, as
      well as immunohistochemistry of multiple human clinical specimens of cancer.
      RESULTS: In immunoblots of whole cell lysates, EG-1 antibodies revealed the
      presence of a 22-kDa peptide. Immunohistochemistry of breast, colon, and prostate
      specimens showed higher levels of EG-1 peptides in cancer tissues, in comparison
      with their benign counterparts. However, EG-1 expression was minimal in both
      benign and malignant lung tissues. CONCLUSIONS: Here, we demonstrated that the
      expression of EG-1 is elevated in cancerous in comparison to benign epithelial
      cells, as seen in immunohistochemistry of human pathological specimens. These
      observations collectively support the hypothesis that the novel gene EG-1 is
      associated with the malignant phenotype of the common epithelial-derived cancers
      of the breast, colon, and prostate.

PMID- 15161709
TI  - pRb2/p130, vascular endothelial growth factor, p27(KIP1), and proliferating cell
      nuclear antigen expression in hepatocellular carcinoma: their clinical
      significance.
AB  - Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million
      fatalities occurring annually worldwide. Multiple risk factors are associated
      with HCC disease etiology, the highest incidence being in patients with chronic
      hepatitis B virus and hepatitis C virus, although other factors such as genetic
      makeup and environmental exposure are involved. Multiple genetic alterations
      including the activation of oncogenes and inactivation of tumor suppressor genes
      are required for malignancy in human cancers and are correlated with increased
      stages of carcinogenesis and further tumor progression. In this study of 21 HCC
      patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF),
      p27((KIP1)), and proliferating cell nuclear antigen as potential HCC molecular
      biomarkers. In our sample set, we found that p27((KIP1)) was absent. Univariate
      survival analysis showed that proliferating cell nuclear antigen expression
      (diffuse staining >50% of positive cells in tumor) was confirmed as a significant
      HCC prognostic biomarker for determining patient survival agreeing with previous
      studies (P = 0.0126, log-rank test). Lower pRb2/p130 expression was associated to
      a borderline P value of inverse correlation with tumor malignancy and to a
      positive correlation with respect to the time from HCC diagnosis (Spearman
      coefficient = 0.568; P < 0.05). Conversely, higher VEGF expression was associated
      with a poor survival (P = 0.0257, log-rank test). We demonstrate for the first
      time that pRb2/p130 is inversely correlated with VEGF expression and tumor
      aggressiveness (P < 0.05) in p27((KIP1))-negative HCC patients. pRb2/p130 and
      VEGF expression are independent from tumor staging, suggesting their possible
      role as independent prognostic molecular biomarkers in HCC. Furthermore, we have
      evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a
      p27((KIP1))-independent manner. Additional studies with larger numbers of patient
      data would allow the use of multivariable techniques and would be able to further
      identify patients with poorer survival.

PMID- 15161710
TI  - The 5A/6A polymorphism of the matrix metalloproteinase 3 gene promoter and breast
      cancer.
AB  - PURPOSE: The matrix metalloproteinase 3 (MMP3), also known as stromelysin-I, is a
      key-player for carcinogenesis and tumor growth. A 5A/6A promoter polymorphism is
      associated with differences in MMP3 activity and has been linked to cancer
      susceptibility in some studies. In the present study we evaluated the role of
      this polymorphism for breast cancer risk. EXPERIMENTAL DESIGN: A case-control
      study was performed including 500 patients with histologically confirmed breast
      cancer and 500 female, age-matched, healthy control subjects from population
      based screening studies. The MMP3 5A/6A polymorphism was determined by a 5'
      nuclease (TaqMan) assay. RESULTS: Prevalences of 5A/5A, 5A/6A, and 6A/6A
      genotypes were similar among patients (20.6, 51.8, and 27.6%, respectively) and
      controls (23.3, 47.3, and 29.4%, P = 0.34). The odds ratio of carriers of a MMP3
      5A allele for breast cancer was 1.09 (95% confidence interval, 0.83-1.44).
      Patients with the 5A/5A genotype had a higher proportion of lymph-node metastases
      than those with a 5A/6A or 6A/6A genotype (P = 0.010). CONCLUSIONS: The MMP3
      5A/6A promoter polymorphism does not appear to influence breast cancer
      susceptibility but may be linked to a higher risk for metastasizing among breast
      cancer patients.

PMID- 15161711
TI  - Expression of the forkhead transcription factor FOXP1 is associated with estrogen
      receptor alpha and improved survival in primary human breast carcinomas.
AB  - PURPOSE: The FOXP1 protein belongs to a functionally diverse family of winged
      helix or forkhead transcription factors that have diverse roles in cellular
      proliferation, differentiation, and neoplastic transformation. The FOXP1 gene,
      which maps to 3p14, shows common loss of heterozygosity in breast tumors and is a
      candidate tumor suppressor gene. However, its role in breast cancer is unknown.
      EXPERIMENTAL DESIGN: We have therefore investigated the pattern of FOXP1
      expression in whole sections from normal (n = 16) and neoplastic (n = 90) breast
      tissues and correlated the level of expression in 283 invasive breast carcinomas
      on tissue microarrays with clinicopathological factors and survival. Because a
      relationship with estrogen receptor (ER) was identified, estrogen (17beta
      estradiol) regulation and ER/FOXP1 colocalization was also investigated. RESULTS:
      Expression of FOXP1 was significantly positively associated with ER (P = 0.03)
      and negatively with epidermal growth factor receptor (P = 0.01) but no
      association with age (P = 0.91), lymph node status (P = 0.94), size (P = 0.76),
      or grade (P = 0.22). In a multivariate analysis of survival, FOXP1 expression was
      associated with a significantly improved relapse-free (P = 0.03) and borderline
      overall (P = 0.09) survival. Unlike normal breast, there was common coexpression
      of FOXP1 and ER in cell lines and tumors, but no 17beta-estradiol (10(-9) m)
      regulation of FOXP1 in MCF-7 cells was demonstrated. CONCLUSIONS: Our findings
      support a role for FOXP1 as a potential ER coregulator in human breast carcinoma
      and suggest that it may also independently regulate additional important pathways
      that control the progression of breast cancer.

PMID- 15161712
TI  - Imatinib mesylate efficiently achieves therapeutic intratumor concentrations in
      vivo but has limited activity in a xenograft model of small cell lung cancer.
AB  - PURPOSE: Despite recent advances in cancer therapy, long-term survival in small
      cell lung cancer (SCLC) remains uncommon, underscoring the need for novel
      therapeutic approaches. Previous studies have identified constitutive expression
      of the receptor tyrosine kinase, c-Kit, and its ligand, stem cell factor, in a
      substantial proportion of SCLC specimens. The purpose of this study was to
      determine whether imatinib mesylate, an inhibitor of c-Kit, could achieve
      therapeutic concentrations in tumors and in brain (a frequent site of SCLC
      metastasis) and interfere with SCLC tumor growth in vivo. EXPERIMENTAL DESIGN:
      Human SCLC tumor cell lines with constitutive c-kit expression and tyrosine
      phosphorylation (NCI-H209, NCI-H526, and NCI-H1607) were used to establish SCLC
      tumor xenografts in NCr nude (nu/nu)-immunodeficient mice. SCLC tumor-bearing
      mice were randomly assigned to imatinib or control (water) administered twice a
      day by oral gavage. Imatinib concentrations in plasma, brain, and tumor were
      quantitated and correlated with tumor response. RESULTS: Therapeutic
      concentrations of imatinib were achieved in plasma and tumor xenografts but not
      in the brain. Imatinib blocked the constitutive activation of c-kit in SCLC tumor
      cell lines in vitro but had a negligible effect on SCLC xenograft growth in vivo.
      CONCLUSIONS: Orally administered imatinib rapidly reaches therapeutic
      concentrations in SCLC xenografts, suggesting the feasibility of combining
      imatinib with other novel or traditional chemotherapeutic agents in SCLC or other
      solid tumors. The c-Kit signaling pathway does not appear to play a critical role
      in SCLC proliferation and viability in vivo, however, suggesting that imatinib is
      unlikely to be effective as monotherapy for SCLC.

PMID- 15161713
TI  - Suppressing orthotopic pancreatic tumor growth with a fiber-modified adenovector
      expressing the TRAIL gene from the human telomerase reverse transcriptase
      promoter.
AB  - An adenoviral vector with RGD-modified fibers and expressing the human tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) gene from the human
      telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD) was
      constructed, and its antitumor activity was evaluated in vitro and in vivo. An in
      vitro study showed that treatment with Ad/TRAIL-F/RGD elicited a high rate of
      apoptosis in human pancreatic and colon cancer cell lines that were either
      susceptible or resistant to conventional adenovectors. In vivo study showed that
      direct administration of Ad/TRAIL-F/RGD to an orthotopic implantation tumor model
      established in the pancreatic tails of nu/nu mice significantly suppressed tumor
      growth: tumors in the animals treated with Ad/TRAIL-F/RGD were approximately
      eight times smaller than those in animals treated with a control vector. We also
      evaluated hTERT promoter activity and the effect of Ad/TRAIL-F/RGD on mesenchymal
      stem cells. Our results showed that transgene expression from the hTERT promoter
      in human bone marrow mesenchymal stem cells was minimal. No adverse effect was
      observed in mesenchymal stem cells treated with Ad/TRAIL-F/RGD. Together, our
      results suggest that Ad/TRAIL-F/RGD could become a potent therapeutic agent for
      the management of pancreatic cancer.

PMID- 15161714
TI  - A comparison of the in vitro and in vivo activities of IgG and F(ab')2 fragments
      of a mixture of three monoclonal anti-Her-2 antibodies.
AB  - PURPOSE: We have demonstrated previously that a mixture of three anti-Her-2
      monoclonal antibodies (MAbs) that bind to different epitopes on the extracellular
      domain of Her-2 expressed on a human breast cancer cell line has more potent
      antitumor activity than the individual MAbs both in vitro and in xenografted
      severe combined immunodeficient mice. Because the activity of Herceptin is Fc
      dependent, we determined whether this would also be the case when a mixture of
      these three anti-Her-2 MAbs was used. EXPERIMENTAL DESIGN: IgG and highly
      purified F(ab')(2) fragments of the anti-Her-2 MAbs and Herceptin were prepared
      and evaluated for their ability to induce cell death, inhibit vascular
      endothelial growth factor secretion, and mediate antibody-dependent cellular
      cytotoxicity and complement-mediated cytotoxicity in vitro. They were also
      compared for their abilities to induce regression of large BT474 tumors in severe
      combined immunodeficient mice. RESULTS: All of the F(ab')(2) fragments were >95%
      pure and, as expected, did not mediate antibody-dependent cellular cytotoxicity
      or complement-dependent cytotoxicity in vitro. The in vitro antiproliferative and
      proapoptotic effects of the IgGs and F(ab')(2) fragments were similar. In
      contrast, the IgGs had significant antitumor activity in vivo, whereas their
      F(ab')(2) fragments were only marginally effective even at 5-fold higher doses to
      offset their shorter half-lives. CONCLUSIONS: These results confirm the
      importance of the Fc portion of Herceptin for optimal in vivo activity and
      demonstrate that even a mixture of three anti-Her-2 MAbs that are highly
      effective at inducing cell death in vitro requires Fc-mediated effector function
      for optimal in vivo activity.

PMID- 15161715
TI  - Improved targeting of pancreatic cancer: experimental studies of a new bispecific
      antibody, pretargeting enhancement system for immunoscintigraphy.
AB  - PURPOSE: The early detection and diagnosis of pancreatic cancer remains a major
      clinical challenge in which imaging procedures have a central role. The purpose
      of this study was to evaluate a pretargeting method with a bispecific PAM4
      (bsPAM4; anti-MUC1) antibody for radioimmunoscintigraphy of experimental human
      pancreatic cancer. EXPERIMENTAL DESIGN: A bispecific F(ab')(2) antibody was
      generated from chimeric PAM4 Fab' and murine 734 (anti-indium
      diethylenetriaminepentaacetic acid) Fab' fragments and then used in conjunction
      with 2 peptide haptens ((111)In-IMP-156 and (99m)Tc-IMP-192). Biodistribution
      studies and radioimmunoscintigraphic imaging properties of the radiolabeled
      bsPAM4, and pretargeted, radiolabeled peptides were examined in the CaPan1 human
      pancreatic tumor grown as s.c. xenografts in athymic nude mice. Tumor uptake and
      tumor:nontumor ratios were compared with a nontargeting irrelevant anti-CD20,
      bispecific rituximab, radiolabeled peptides alone, and with directly labeled
      PAM4. RESULTS: Biodistribution results indicated significantly greater tumor
      uptake of radiolabeled peptides at 3 h after injection when pretargeting was
      performed with bsPAM4 as compared with the bispecific rituximab [20.2 +/- 5.5
      percentage of injected dose per gram of tissue (%ID/g) versus 0.9 +/- 0.1%ID/g,
      respectively, for (111)In-IMP-156, and 16.8 +/- 4.8%ID/g versus 1.1 +/- 0.2%ID/g,
      respectively, for (99m)Tc-IMP-192]. Similar results were obtained at the 24-h
      time point. Tumor:nontumor ratios were >30 for all of the tissues except the
      kidneys, where a ratio of 7.8 +/- 2.8 was observed. By immunoscintigraphy, tumors
      could be visualized as early as 30 min after injection of the radiolabeled
      peptide. CONCLUSIONS: These studies demonstrate the feasibility of using the
      pretargeted, bispecific antibody technology for nuclear imaging of pancreatic
      cancer. The advantage of pretargeted bsPAM4 antibody as an imaging platform is
      the high specificity for pancreatic cancer as compared with the physicochemical
      parameters identified by current imaging technologies.

PMID- 15161716
TI  - The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptosis in
      response to antimetabolites.
AB  - Fas (CD95/Apo-1) is a member of the tumor necrosis factor receptor family.
      Receptor binding results in activation of caspase 8, leading to activation of
      proapoptotic downstream molecules. We found that expression of Fas was up
      regulated >10-fold in MCF-7 breast and HCT116 and RKO colon cancer cell lines
      after treatment with IC(60) doses of 5-fluorouracil (5-FU) and raltitrexed (RTX).
      Combined treatment with the agonistic Fas antibody CH-11 and either 5-FU or RTX
      resulted in a highly synergistic induction of apoptosis in these cell lines.
      Similar results were obtained for another antifolate, Alimta. Induction of
      thymidylate synthase expression inhibited Fas induction in response to RTX and
      Alimta, but not in response to 5-FU. Furthermore, thymidylate synthase induction
      abrogated the synergy between CH-11 and both antifolates but had no effect on the
      synergistic interaction between 5-FU and CH-11. Inactivation of p53 in MCF-7 and
      HCT116 cell lines blocked 5-FU- and antifolate-mediated up-regulation of Fas.
      Furthermore, Fas was not up-regulated in response to 5-FU or antifolates in the
      p53-mutant H630 colon cancer cell line. Lack of Fas up-regulation in the p53-null
      and -mutant lines abolished the synergistic interaction between 5-FU and CH-11.
      Interestingly, synergy was still observed between the antifolates and CH-11 in
      the p53-null HCT116 and p53-mutant H630 cell lines, although this was
      significantly reduced compared with the p53 wild-type cell lines. Our results
      indicate that Fas is an important mediator of apoptosis in response to both 5-FU
      and antifolates.

PMID- 15161717
TI  - Confirmation of the activity of the interleukin-2 fusion toxin denileukin
      diftitox against chemorefractory chronic lymphocytic leukemia, including cases
      with chromosome 17p deletions and without detectable CD25 expression.

PMID- 15161718
TI  - A Rosetta stone for insulin treatment: self-monitoring of blood glucose.

PMID- 15161719
TI  - On-site quantification of human urinary albumin by a fluorescence immunoassay.

PMID- 15161720
TI  - Evaluation of human chorionic gonadotropin beta-subunit mRNA concentrations in
      maternal serum in aneuploid pregnancies: a feasibility study.

PMID- 15161721
TI  - Universal sensing strategy for the detection of nucleic acid targets by optical
      biosensor based on surface plasmon resonance.

PMID- 15161722
TI  - Molecular beacons for multiplex detection of four bacterial bioterrorism agents.

PMID- 15161723
TI  - Ischemia-modified albumin during skeletal muscle ischemia.

PMID- 15161724
TI  - DNA methylation changes in sera of women in early pregnancy are similar to those
      in advanced breast cancer patients.

PMID- 15161725
TI  - Standardized evaluation of instruments for self-monitoring of blood glucose by
      patients and a technologist.

PMID- 15161727
TI  - Use of PCR-based amplification analysis as a substitute for the southern blot
      method for CYP21 deletion detection in congenital adrenal hyperplasia.

PMID- 15161728
TI  - Optimum collection and storage conditions for ghrelin measurements: octanoyl
      modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood
      samples.

PMID- 15161726
TI  - Elimination of the cardiac natriuretic peptides B-type natriuretic peptide (BNP)
      and N-terminal proBNP by hemodialysis.

PMID- 15161729
TI  - Substitution of 3'-phosphate cap with a carbon-based blocker reduces the
      possibility of fluorescence resonance energy transfer probe failure in real-time
      PCR assays.

PMID- 15161730
TI  - Microsatellite instability in colorectal cancer: considerations for molecular
      diagnosis and high-throughput screening of archival tissues.

PMID- 15161731
TI  - Rapid, simple laser-light-scattering method for HDL particle sizing in whole
      plasma.

PMID- 15161732
TI  - Quantitative assessment of PML-RARa and BCR-ABL by two real-time PCR instruments:
      multiinstitutional laboratory trial.

PMID- 15161733
TI  - Size-selective extraction of peptides from urine for mass spectrometric analysis.

PMID- 15161734
TI  - Haptoglobin phenotypes in epilepsy.

PMID- 15161735
TI  - Pitfall in HPLC assay for urinary metanephrines: an unusual type of interference
      caused by methenamine intake.

PMID- 15161736
TI  - Serum protein electrophoresis: reptilase treatment is superior to ethanol
      precipitation for specific removal of fibrinogen from heparinized plasma samples.

PMID- 15161737
TI  - The interfering component in cardiac troponin I immunoassays.

PMID- 15161738
TI  - How much "urinary free cortisol" is really cortisol during water diuresis in
      healthy individuals?

PMID- 15161739
TI  - Preliminary evaluation of the AxSYM B-type natriuretic peptide (BNP) assay and
      comparison with the ADVIA Centaur BNP assay.

PMID- 15161740
TI  - Bicarbonate interference with chloride-ion-selective electrodes.

PMID- 15161741
TI  - Human pancreatic duct cells exert tissue factor-dependent procoagulant activity:
      relevance to islet transplantation.
AB  - Activation of the coagulation cascade contributes to early graft loss and
      intraportal thrombotic events in clinical islet transplantation. Although these
      complications were shown to be related to the presence of tissue factor in human
      islet preparations, the contribution of duct cells, which represent a major
      contaminant of clinical islet isolates, has not been specified so far. Herein, we
      used flow cytometry, immunohistochemistry, RT-PCR, and functional coagulation
      assays to demonstrate that duct cells exert a potent factor VII-dependent
      procoagulant activity related to their expression of tissue factor. Both the
      classical membrane-bound and the recently described soluble form of tissue factor
      were shown to be synthesized by duct cells. We conclude that contaminating duct
      cells contribute to early beta-cell damage after islet transplantation through
      their involvement in tissue factor-mediated thrombotic and inflammatory events.

PMID- 15161742
TI  - Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes.
AB  - Recent evidence points toward decreased oxidative capacity and mitochondrial
      aberrations as a major contributor to the development of insulin resistance and
      type 2 diabetes. In this article we will provide an integrative view on the
      interrelation between decreased oxidative capacity, lipotoxicity, and
      mitochondrial aberrations in type 2 diabetes. Type 2 diabetes is characterized by
      disturbances in fatty acid metabolism and is accompanied by accumulation of fatty
      acids in nonadipose tissues. In metabolically active tissues, such as skeletal
      muscle, fatty acids are prone to so-called oxidative damage. In addition to
      producing energy, mitochondria are also a major source of reactive oxygen
      species, which can lead to lipid peroxidation. In particular, the mitochondrial
      matrix, which contains DNA, RNA, and numerous enzymes necessary for substrate
      oxidation, is sensitive to peroxide-induced oxidative damage and needs to be
      protected against the formation and accumulation of lipids and lipid peroxides.
      Recent evidence reports that mitochondrial uncoupling is involved in the
      protection of the mitochondrial matrix against lipid-induced mitochondrial
      damage. Disturbances in this protection mechanism can contribute to the
      development of type 2 diabetes.

PMID- 15161743
TI  - Microvascular recruitment is an early insulin effect that regulates skeletal
      muscle glucose uptake in vivo.
AB  - Insulin increases glucose disposal into muscle. In addition, in vivo insulin
      elicits distinct nitric oxide synthase-dependent vascular responses to increase
      total skeletal muscle blood flow and to recruit muscle capillaries (by relaxing
      resistance and terminal arterioles, respectively). In the current study, we
      compared the temporal sequence of vascular and metabolic responses to a 30-min
      physiological infusion of insulin (3 mU. min(-1). kg(-1), euglycemic clamp) or
      saline in rat skeletal muscle in vivo. We used contrast-enhanced ultrasound to
      continuously quantify microvascular volume. Insulin recruited microvasculature
      within 5-10 min (P < 0.05), and this preceded both activation of insulin
      signaling pathways and increases in glucose disposal in muscle, as well as
      changes in total leg blood flow. Moreover, l-NAME (N(omega)-nitro-l-arginine
      methyl ester), a specific inhibitor of nitric oxide synthase, blocked this early
      microvascular recruitment (P < 0.05) and at least partially inhibited early
      increases in muscle glucose uptake (P < 0.05). We conclude that insulin rapidly
      recruits skeletal muscle capillaries in vivo by a nitric oxide-dependent action,
      and the increase in capillary recruitment may contribute to the subsequent
      glucose uptake.

PMID- 15161744
TI  - Relationship between serum amyloid A level and Tanis/SelS mRNA expression in
      skeletal muscle and adipose tissue from healthy and type 2 diabetic subjects.
AB  - Tanis is a recently described protein reported to be a putative receptor for
      serum amyloid A and found to be dysregulated with diabetes in the Israeli sand
      rat Psamommys obesus. Tanis has also been identified as a selenoprotein, one of
      the first two identified membrane selenoproteins. We determined mRNA expression
      of the human homologue of Tanis, SelS/AD-015, in skeletal muscle and adipose
      tissue biopsies obtained from 10 type 2 diabetic patients and 11 age- and weight
      matched healthy subjects. Expression of Tanis/SelS mRNA in skeletal muscle and
      adipose tissue biopsies was similar between diabetic and control subjects. A
      subset of subjects underwent a euglycemic-hyperinsulinemic clamp, and adipose
      tissue expression of Tanis/SelS was determined after in vivo insulin stimulation.
      Adipose tissue Tanis/SelS mRNA expression was unchanged after insulin infusion in
      control subjects, whereas Tanis/SelS mRNA increased in seven of eight subjects
      following insulin stimulation in diabetic subjects. Skeletal muscle and adipose
      tissue Tanis/SelS mRNA expression were positively correlated with plasma serum
      amyloid A. In conclusion, there is a strong trend toward upregulation of
      Tanis/SelS following insulin infusion in adipose tissue from type 2 diabetic
      subjects. Moreover, the positive relationship between Tanis mRNA and the acute
      phase protein serum amyloid A suggests an interaction between innate immune
      system responses and Tanis expression in muscle and adipose tissue.

PMID- 15161745
TI  - AMP kinase-induced skeletal muscle glucose but not long-chain fatty acid uptake
      is dependent on nitric oxide.
AB  - The purpose of this study was to examine the effects of AMP kinase (AMPK)
      activation on in vivo glucose and long-chain fatty acid (LCFA) uptake in skeletal
      muscle and to examine the nitric oxide (NO) dependence of any putative effects.
      Catheters were chronically implanted in the carotid artery and jugular vein of
      male Sprague-Dawley rats. After 4 days of recovery, rats were given either water
      or water containing 1 mg/ml nitro-l-arginine methylester (l-NAME) for 2.5 days.
      After an overnight fast, rats underwent one of five protocols: saline, 5
      aminoimidazole-4-carboxamide-1-B-d-ribofuranoside (AICAR) (10 mg. kg(-1). min(
      1)), l-NAME, AICAR + l-NAME, or AICAR + Intralipid (20%, 0.02 ml. kg(-1). min(
      1)). Glucose was clamped at approximately 6.5 mmol/l in all groups, and an
      intravenous bolus of 2-deoxy[(3)H]glucose and [(125)I]-15-(p-iodophenyl)-3-R,S
      methylpentadecanoic acid was administered to obtain indexes of glucose (K(g)) and
      LCFA (K(f)) uptake and clearance. At 150 min, soleus, gastrocnemius, and
      superficial vastus lateralis were excised for tracer determination. Both K(g) and
      K(f) increased with AICAR in all muscles studied. K(g) decreased with increasing
      muscle composition of type 1 slow-twitch fibers, whereas K(f) increased. In
      addition, AICAR-induced increases in K(g) but not K(f) were abolished by l-NAME
      in the majority of muscles examined. This shows that the mechanisms by which AMPK
      stimulates glucose and LCFA uptake are distinct.

PMID- 15161746
TI  - Effects of insulin, contraction, and phorbol esters on mitogen-activated protein
      kinase signaling in skeletal muscle from lean and ob/ob mice.
AB  - Effects of diverse stimuli, including insulin, muscle contraction, and phorbol 12
      myristate-13-acetate (PMA), were determined on phosphorylation of mitogen
      activated protein kinase (MAPK) signaling modules (c-Jun NH(2)-terminal kinase
      [JNK], p38 MAPK, and extracellular signal-related kinase [ERK1/2]) in skeletal
      muscle from lean and ob/ob mice. Insulin increased phosphorylation of JNK, p38
      MAPK, and ERK1/2 in isolated extensor digitorum longus (EDL) and soleus muscle
      from lean mice in a time- and dose-dependent manner. Muscle contraction and PMA
      also elicited robust effects on these parallel MAPK modules. Insulin action on
      JNK, p38 MAPK, and ERK1/2 phosphorylation was significantly impaired in EDL and
      soleus muscle from ob/ob mice. In contrast, muscle contraction-mediated JNK, p38
      MAPK, and ERK1/2 phosphorylation was preserved. PMA effects on phosphorylation of
      JNK and ERK1/2 were normal in ob/ob mice, whereas effects on p38 MAPK were
      abolished. In conclusion, insulin, contraction, and PMA activate MAPK signaling
      in skeletal muscle. Insulin-mediated responses on MAPK signaling are impaired in
      skeletal muscle from ob/ob mice, whereas the effect of contraction is generally
      well preserved. In addition, PMA-induced phosphorylation of JNK and ERK1/2 are
      preserved, whereas p38 MAPK pathways are impaired in skeletal muscle from ob/ob
      mice. Thus, appropriate MAPK responses can be elicited in insulin-resistant
      skeletal muscle via an insulin-independent mechanism.

PMID- 15161747
TI  - Role of adipocyte-derived factors in enhancing insulin signaling in skeletal
      muscle and white adipose tissue of mice lacking Acyl CoA:diacylglycerol
      acyltransferase 1.
AB  - Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in
      mammalian triglyceride synthesis, have decreased adiposity and increased insulin
      sensitivity. Here we show that insulin-stimulated glucose transport is increased
      in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-deficient
      mice. This increase in glucose transport correlated with enhanced insulin
      stimulated activities of phosphatidylinositol 3-kinase, protein kinase B (or
      Akt), and protein kinase Clambda (PKC-lambda), three key molecules in the insulin
      signaling pathway, and was associated with decreased levels of serine
      phosphorylated insulin receptor substrate 1 (IRS-1), a molecule implicated in
      insulin resistance. Similar findings in insulin signaling were also observed in
      DGAT1-deficient mice fed a high-fat diet. Interestingly, the increased PKC-lambda
      activity and decreased serine phosphorylation of IRS-1 were observed in chow-fed
      wild-type mice transplanted with DGAT1-deficient WAT, consistent with our
      previous finding that transplantation of DGAT1-deficient WAT enhances glucose
      disposal in wild-type recipient mice. Our findings demonstrate that DGAT1
      deficiency enhances insulin signaling in the skeletal muscle and WAT, in part
      through altered expression of adipocyte-derived factors that modulate insulin
      signaling in peripheral tissues.

PMID- 15161748
TI  - Advanced glycation end products modulate the maturation and function of
      peripheral blood dendritic cells.
AB  - Advanced glycation end products (AGEs), a complex and heterogeneous group of
      posttranslational modifications of proteins in vivo, have been widely studied for
      their involvement in diabetic complications; these complications are largely
      vascular and accompanied by inflammation. Because dendritic cells (DCs) initiate
      and modulate inflammatory responses, we hypothesized that AGEs might exert
      immunomodulatory effects via antigen-presenting DCs. To test this hypothesis, we
      investigated effects of the AGE peptide, compared with the naked peptide, on
      maturation, costimulatory molecule expression, and function of DCs in peripheral
      blood. From flow cytometry, we found a dose-dependent inhibition in CD83
      expression on DCs exposed for 2.5 h to each of two synthetic AGE peptides. A
      similar culture for 24 h additionally produced an inhibition of CD80 expression,
      whereas exposure to AGEs for 3 days induced a large increase in DC numbers and a
      concomitant loss of monocyte/macrophages. Exposure of DCs to AGEs resulted in a
      dose-dependent loss in their capacity to stimulate primary proliferation of
      allogeneic T-cells. We conclude that AGEs promote development of DCs but that
      these DCs fail to express maturation markers and lose the capacity to stimulate
      primary T-cell responses. Effects of AGEs on DCs could be instrumental in the
      immunological changes associated with diabetes.

PMID- 15161749
TI  - Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real
      time.
AB  - Development of autoimmune diabetes in both humans and mice is preceded by a
      prolonged period of inflammation of pancreatic islets by autoreactive T-cells.
      Noninvasive imaging techniques, including positron-emission tomography and
      optical or magnetic resonance imaging, have been used to track the recruitment of
      lymphocytes to sites of inflammation. These techniques, however, rely on labeling
      strategies that are non-antigen specific and do not allow specific tracking of
      the recruitment of autoreactive lymphocytes. Here we describe an antigen-specific
      magnetic label to selectively target a prevalent population of diabetogenic
      CD8(+) T-cells that contribute to the progression of insulitis to overt diabetes
      in NOD mice. Superparamagnetic nanoparticles coated with multiple copies of a
      high-avidity peptide/major histocompatibility complex ligand of these T-cells
      (NRP-V7/K(d)) are endocytosed by CD8(+) T-cells in an antigen-specific manner.
      Using these T-cells as probes, we show that inflammation of pancreatic islets by
      autoreactive T-cells can be detected in real time by magnetic resonance imaging.
      This study demonstrates the feasibility of visualizing the presence of ongoing
      autoimmune responses noninvasively.

PMID- 15161751
TI  - The role of calcium/calmodulin-dependent protein kinase cascade in glucose
      upregulation of insulin gene expression.
AB  - A number of factors have been reported to affect insulin synthesis in beta-cells.
      Although glucose is the most important regulator of insulin gene expression in
      pancreatic beta-cells, the mechanisms whereby glucose stimulates insulin gene
      transcription in response to changes in glucose concentration have not been
      clarified yet. In this study, we examined the role of the Ca(2+)/calmodulin (CaM)
      dependent protein kinase (CaM-K) cascade in transcriptional activation of
      insulin. RT-PCR, Western blotting, and immunohistochemical staining analysis
      revealed that CaM-K kinase-alpha (CaM-KKalpha) and CaM-KIV were localized in rat
      pancreatic beta-cells and their cell line, INS-1. Exposure of INS-1 cells to 11.2
      mmol/l glucose elicited an increase of insulin promoter activity as well as
      upregulation of CaM-KIV activity within 2 min after stimulation. We investigated
      the influence on insulin promoter activity of the constitutively active form (CaM
      KIVc) or dominant-negative mutant (CaM-KIVdn) of CaM-KIV in transfected INS-1
      cells. CaM-KIVc alone was sufficient, and the upstream kinase, CaM-KK, was
      enhanced to upregulate the insulin promoter activity in INS-1 cells. Furthermore,
      cotransfection of CaM-KIVdn suppressed to a significant degree the glucose
      upregulated activity of the insulin promoter. Taken together, these results
      indicated that the CaM-KK/CaM-KIV cascade might play an important role in glucose
      upregulated transcriptional activation of the insulin gene.

PMID- 15161750
TI  - Changes in the dimeric state of neuronal nitric oxide synthase affect the
      kinetics of secretagogue-induced insulin response.
AB  - We previously showed that pancreatic beta-cells express a neuronal isoform of
      nitric oxide synthase (nNOS) that controls insulin secretion by exerting two
      enzymatic activities: nitric oxide (NO) production and cytochrome c reductase
      activity. We now bring evidence that two inhibitors of nNOS, N-omega-nitro-l
      arginine methyl ester (l-NAME) and 7-nitroindazole (7-NI), increase glucose
      induced insulin secretion but affect beta-cell function differently. In the
      presence of l-NAME, insulin response is monophasic, whereas 7-NI preserves the
      normal biphasic secretory pattern. In addition, the alterations of beta-cell
      functional response induced by the inhibitors also differ by their sensitivity to
      a substitutive treatment with sodium nitroprusside, a chemical NO donor. These
      differences are probably related to the nature of the two inhibitors. Indeed,
      using low-temperature SDS-PAGE and real-time analysis of nNOS dimerization by
      surface plasmon resonance, we could show that 7-NI, which competes with arginine
      and tetrahydrobiopterin (BH(4)), an essential cofactor for nNOS dimer formation,
      inhibits dimerization of the enzyme, whereas the substrate-based inhibitor l-NAME
      stabilizes the homodimeric state of nNOS. The latter effect could be reproduced
      by the two endogenous inhibitors of NOS, N-omega-methyl-l-arginine and asymmetric
      dimethylarginine, and resulted interestingly in a reduced ability of the protein
      inhibitor of nNOS (PIN) to dissociate nNOS dimers. We conclude that intracellular
      factors able to induce abnormalities in the nNOS monomer/dimer equilibrium could
      lead to pancreatic beta-cell dysfunction.

PMID- 15161752
TI  - Regulation of alpha-cell function by the beta-cell during hypoglycemia in Wistar
      rats: the "switch-off" hypothesis.
AB  - The glucagon response is the first line of defense against hypoglycemia and is
      lost in insulin-dependent diabetes. The beta-cell "switch-off" hypothesis
      proposes that a sudden cessation of insulin secretion from beta-cells into the
      portal circulation of the islet during hypoglycemia is a necessary signal for the
      glucagon response from downstream alpha-cells. Although indirect evidence exists
      to support this hypothesis, it has not been directly tested in vivo by provision
      and then discontinuation of regional reinsulinization of alpha-cells at the time
      of a hypoglycemic challenge. We studied streptozotocin (STZ)-induced diabetic
      Wistar rats that had no glucagon response to a hypoglycemic challenge. We
      reestablished insulin regulation of the alpha-cell by regionally infusing insulin
      (0.025 microU/min) directly into the superior pancreaticoduodenal artery (SPDa)
      of STZ-administered rats at an infusion rate that did not alter systemic venous
      glucose levels. SPDa insulin infusion was switched off simultaneously when blood
      glucose fell to <60 mg/dl after a jugular venous insulin injection. This maneuver
      restored the glucagon response to hypoglycemia (peak change within 5-10 min = 326
      +/- 98 pg/ml, P < 0.05; and peak change within 15-20 min = 564 +/- 148 pg/ml, P <
      0.01). No response was observed when the SPDa insulin infusion was not turned off
      (peak change within 5-10 min = 44 +/- 85 pg/ml, P = NS; and peak change within 15
      20 min = 67 +/- 97 pg/ml, P = NS) or when saline instead of insulin was infused
      and then switched off (peak change within 5-10 min = -44 +/- 108 pg/ml, P = NS;
      and peak change within 15-20 min = -13 +/- 43 pg/ml, P = NS). No responses were
      observed during euglycemia (peak change within 5-10 min = 48 +/- 35 pg/ml, P =
      NS; and peak change within 15-20 min = 259 +/- 129 pg/ml, P = NS) or
      hyperglycemia (peak change within 5-10 min = 49 +/- 62 pg/ml, P = NS; and peak
      change within 15-20 min = 138 +/- 87 pg/ml, P = NS). Thus, the glucagon response
      to hypoglycemia that was absent in rats made diabetic by STZ was restored by
      regional infusion and then discontinuation of insulin. These data provide direct
      in vivo support for the beta-cell "switch-off" hypothesis and indicate that the
      alpha-cell is not intrinsically abnormal in insulin-dependent diabetes because of
      STZ-induced destruction of beta-cells.

PMID- 15161753
TI  - Regulation of alpha-cell function by the beta-cell in isolated human and rat
      islets deprived of glucose: the "switch-off" hypothesis.
AB  - The "switch-off" hypothesis to explain beta-cell regulation of alpha-cell
      function during hypoglycemia has not been assessed previously in isolated islets,
      largely because they characteristically do not respond to glucose deprivation by
      secreting glucagon. We examined this hypothesis using normal human and Wistar rat
      islets, as well as islets from streptozotocin (STZ)-administered beta-cell
      deficient Wistar rats. As expected, islets perifused with glucose and 3-isobutryl
      1-methylxanthine did not respond to glucose deprivation by increasing glucagon
      secretion. However, if normal rat islets were first perifused with 16.7 mmol/l
      glucose to increase endogenous insulin secretion, followed by discontinuation of
      the glucose perifusate, a glucagon response to glucose deprivation was observed
      (peak change within 10 min after switch off = 61 +/- 15 pg/ml [mean +/- SE], n =
      6, P < 0.01). A glucagon response from normal human islets using the same
      experimental design was also observed. A glucagon response (peak change within 7
      min after switch off = 31 +/- 1 pg/ml, n = 3, P < 0.01) was observed from beta
      cell-depleted, STZ-induced diabetic rats whose islets still secreted small
      amounts of insulin. However, when these islets were first perifused with both
      exogenous insulin and 16.7 mmol/l glucose, followed by switching off both the
      insulin and glucose perifusate, a significantly larger (P < 0.05) glucagon
      response was observed (peak change within 7 min after switch off = 71 +/- 11
      pg/ml, n = 4, P < 0.01). This response was not observed if the insulin perifusion
      was not switched off when the islets were deprived of glucose or when insulin was
      switched off without glucose deprivation. These data uniquely demonstrate that
      both normal, isolated islets and islets from STZ-administered rats can respond to
      glucose deprivation by releasing glucagon if they are first provided with
      increased endogenous or exogenous insulin. These results fully support the beta
      cell switch-off hypothesis as a key mechanism for the alpha-cell response to
      hypoglycemia.

PMID- 15161754
TI  - Glucose and insulin treatment of insulinoma cells results in transcriptional
      regulation of a common set of genes.
AB  - Glucose and insulin are important regulators of islet beta-cell growth and
      function by activating signaling pathways resulting in transcriptional changes
      that lead to adaptive responses. Several immediate early genes have been shown to
      be rapidly induced by glucose-activated depolarization in islet beta-cells. The
      current studies address aspects of glucose-regulated transcription: 1) the number
      and characteristics of these genes, 2) if depolarization is the major mechanism,
      and 3) if glucose-stimulated insulin secretion is responsible, because insulin
      per se can activate transcription. Here, the expression profiles of glucose
      responsive insulinoma cells 45 min after the addition of glucose, KCl to induce
      depolarization, or insulin were assessed by endocrine pancreas cDNA microarrays.
      Glucose activated more than 90 genes, representing diverse gene ontology
      functions, and most were not previously known to be glucose responsive. KCl
      activated 80% of these same glucose-regulated genes and, along with the effects
      of pretreatment with diazoxide, suggested that glucose signaling is mediated
      primarily via depolarization. There were >150 genes activated by insulin, and
      remarkably 71% were also regulated by glucose. Preincubation with a
      phosphatidylinositol (PI) 3-kinase inhibitor resulted in almost total inhibition
      of depolarization and insulin-activated transcriptional responses. Thus, through
      gene expression profiling, these data demonstrate that glucose and insulin
      rapidly activate a PI 3-kinase pathway, resulting in transcription of a common
      set of genes. This is consistent with glucose activation of gene transcription
      either directly or indirectly through a paracrine/autocrine effect via insulin
      release. These results illustrate that expression gene profiling can contribute
      to the elucidation of important beta-cell biological functions.

PMID- 15161755
TI  - Diabetes due to a progressive defect in beta-cell mass in rats transgenic for
      human islet amyloid polypeptide (HIP Rat): a new model for type 2 diabetes.
AB  - The islet in type 2 diabetes is characterized by a deficit in beta-cell mass,
      increased beta-cell apoptosis, and impaired insulin secretion. Also, islets in
      type 2 diabetes often contain deposits of islet amyloid derived from islet
      amyloid polypeptide (IAPP), a 37-amino acid protein cosecreted with insulin by
      beta-cells. Several lines of evidence suggest that proteins with a capacity to
      develop amyloid fibrils may also form small toxic oligomers that can initiate
      apoptosis. The amino acid sequence of IAPP in rats and mice is identical and
      differs from that in humans by substitution of proline residues in the
      amyloidogenic sequence so that the protein no longer forms amyloid fibrils or is
      cytotoxic. In the present study, we report a novel rat model for type 2 diabetes:
      rats transgenic for human IAPP (the HIP rat). HIP rats develop diabetes between 5
      and 10 months of age, characterized by an approximately 60% deficit in beta-cell
      mass that is due to an increased frequency of beta-cell apoptosis. HIP rats
      develop islet amyloid, but the extent of amyloid was not related to the frequency
      of beta-cell apoptosis (r = 0.10, P = 0.65), whereas the fasting blood glucose
      was (r = 0.77, P < 0.001). The frequency of beta-cell apoptosis was related to
      the frequency of beta-cell replication (r = 0.97, P < 0.001) in support of the
      hypothesis that replicating cells are more vulnerable to apoptosis than
      nondividing cells. The HIP rat provides additional evidence in support of the
      potential role of IAPP oligomer formation toward the increased frequency of
      apoptosis in type 2 diabetes, a process that appears to be compounded by glucose
      toxicity when hyperglycemia supervenes.

PMID- 15161756
TI  - Islet secretory defect in insulin receptor substrate 1 null mice is linked with
      reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+
      ATPase (SERCA)-2b and -3.
AB  - Mice with deletion of insulin receptor substrate (IRS)-1 (IRS-1 knockout [KO]
      mice) show mild insulin resistance and defective glucose-stimulated insulin
      secretion and reduced insulin synthesis. To further define the role of IRS-1 in
      islet function, we examined the insulin secretory defect in the knockouts using
      freshly isolated islets and primary beta-cells. IRS-1 KO beta-cells exhibited a
      significantly shorter increase in intracellular free Ca(2+) concentration
      ([Ca(2+)](i)) than controls when briefly stimulated with glucose or
      glyceraldehyde and when l-arginine was used to potentiate the stimulatory effect
      of glucose. These changes were paralleled by a lower number of exocytotic events
      in the KO beta-cells in response to the same secretagogues, indicating reduced
      insulin secretion. Furthermore, the normal oscillations in intracellular Ca(2+)
      and O(2) consumption after glucose stimulation were dampened in freshly isolated
      KO islets. Semiquantitative RT-PCR showed a dramatically reduced islet expression
      of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)-2b and -3 in the mutants.
      These data provide evidence that IRS-1 modulation of insulin secretion is
      associated with Ca(2+) signaling and expression of SERCA-2b and -3 genes in
      pancreatic islets and provides a direct link between insulin resistance and
      defective insulin secretion.

PMID- 15161757
TI  - Regulation of rat pancreatic CCKB receptor and somatostatin expression by
      insulin.
AB  - The cholecystokinin B receptor (CCK(B)R) is localized on pancreatic endocrine
      somatostatin delta-cells. Pancreatic somatostatin content was increased in
      diabetic rats. The mechanisms involved in this phenomenon are unknown, and we
      believe insulin is involved. In this study, four groups of rats were used:
      controls, streptozotocin-induced diabetic, streptozotocin-induced diabetic with
      insulin, and streptozotocin-induced diabetic with insulin and its cessation. Rats
      were killed after 7-28 days of treatment for diabetes, and somatostatin mRNA
      expression and pancreatic somatostatin content, CCK(B)R mRNA and protein
      expression evaluation in total pancreas and purified islets, and the cellular
      localization of somatostatin and CCK(B)R in islets was measured. Data indicate
      that diabetes is established after 7 days, is controlled by insulin, and
      reappears after treatment cessation. Pancreatic somatostatin mRNA expression and
      somatostatin content were increased during diabetes, normalized during insulin
      treatment, and reaugmented after treatment cessation. Gland and islet CCK(B)R
      mRNA and protein almost disappeared during diabetes; CCK(B) mRNA reappeared in
      response to insulin, but the protein did not. Confocal microscopy confirmed data
      obtained on somatostatin and CCK(B)R as established biochemically in the course
      of the treatments. In conclusion, these data strongly suggest that insulin can
      negatively control pancreatic somatostatin mRNA and hormone content and
      positively control CCK(B)R mRNA; the CCK(B)R protein appears to be delayed.

PMID- 15161758
TI  - Influence of autonomic neuropathy on QTc interval lengthening during hypoglycemia
      in type 1 diabetes.
AB  - Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of
      arrhythmia risk and sudden death. This results from both sympatho-adrenal
      activation and a lowered serum potassium. It has been suggested that cardiac
      autonomic neuropathy (CAN) might indicate those who are at particular risk. We
      tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic
      control subjects. After standard tests of autonomic function and baroreflex
      sensitivity (BRS) measurement, diabetic participants were divided into three
      groups: 1) CAN- with normal BRS (BRS+; n = 10), 2) CAN- with impaired BRS (BRS-;
      n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia
      (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (+/-SE) QTc lengthened from 377
      +/- 9 ms (baseline) to a maximum during hypoglycemia of 439 +/- 13 ms in BRS+
      subjects and from 378 +/- 5 to 439 +/- 10 ms in control subjects. Peak QTc tended
      to be lower in CAN+ (baseline, 383 +/- 6; maximum, 408 +/- 10) and BRS- groups
      (baseline, 380 +/- 8; maximum, 421 +/- 11; F = 1.7, P = 0.18). Peak epinephrine
      concentrations (nmol/l) were 3.1 +/- 0.8 (BRS+), 2.6 +/- 0.5 (BRS-), 1.4 +/- 0.3
      (CAN+), and 5.7 +/- 0.8 (control subjects). These data do not indicate that those
      with CAN are at particular risk for abnormal cardiac repolarization during
      hypoglycemia. Indeed, they suggest that such patients may be relatively
      protected, perhaps as a result of attenuated sympatho-adrenal responses.

PMID- 15161759
TI  - Muscle strength in type 2 diabetes.
AB  - Motor function in type 2 diabetes is largely unknown. In 36 type 2 diabetic
      patients and in 36 control subjects matched for sex, age, weight, height, and
      physical activity, strength of flexors and extensors at elbow, wrist, knee, and
      ankle was assessed at isokinetic dynamometry. The degree of neuropathy was
      determined by clinical scores, nerve conduction studies, and quantitative sensory
      testing. Eventually, all results were summed to obtain a neuropathy rank-sum
      score (NRSS). The degree of nephropathy and retinal condition were also
      evaluated. Diabetic patients had a 17 and 14% reduction of strength of ankle
      flexors (P < 0.02) and ankle extensors (P < 0.03), respectively. At the knee,
      strength of extensors and flexors was reduced by 7% (NS) and 14% (P < 0.05),
      respectively. At the elbow and wrist, muscle strength was preserved. The NRSS was
      related to the strength at the ankle (r = -0.45, P < 0.01) and knee (r = -0.42, P
      < 0.02). Following multiple regression analysis, the NRSS but not the degree of
      nephropathy or retinopathy was related to strength at the ankle and knee. In
      conclusion, type 2 diabetic patients may have muscle weakness at the ankle and
      knee related to presence and severity of peripheral neuropathy.

PMID- 15161760
TI  - Differences in insulin resistance in nondiabetic subjects with isolated impaired
      glucose tolerance or isolated impaired fasting glucose.
AB  - Both impaired glucose tolerance (IGT) (as defined by the 1985 World Health
      Organization criteria) and impaired fasting glucose (IFG) (as defined by the 1997
      American Diabetes Association criteria) represent intermediate metabolic states
      between normal and diabetic glucose homeostasis. Cardiovascular disease may be
      related to postglucose load rather than fasting glycemia, i.e., IGT rather than
      IFG. We hypothesized that subjects with IGT may be more insulin resistant and
      have higher levels of common cardiovascular risk factors than those with isolated
      IFG. In the Insulin Resistance Atherosclerosis Study (IRAS), we studied S(i) and
      first-phase insulin secretion (acute insulin response [AIR]), as derived from a
      frequently sampled intravenous glucose tolerance test, as well as common
      cardiovascular risk factors in four different glucose tolerance categories
      (NFG/NGT [n = 654], NFG/IGT [n = 255], IFG/NGT [n = 59], and IFG/IGT [n = 102])
      among nondiabetic subjects. Subjects with isolated postchallenge hyperglycemia
      (NFG/IGT) had lower S(i) (means +/- SE: 2.10 +/- 0.04 vs. 2.59 +/- 0.13 x 10(-4)
      min(-1). microU(-1). ml(-1); P = 0.005), lower proinsulin levels (34.4 +/- 1.8
      vs. 42.0 +/- 4.5 pmol/l; P = 0.03), higher AIR (273.1 +/- 18.1 vs. 215.9 +/- 30.0
      pmol/l; P = 0.04), higher C-reactive protein (2.49 +/- 0.3 vs. 1.49 +/- 0.5 mg/l;
      P = 0.0015), and higher triglyceride levels (137.7 +/- 5.5 vs. 108.4 +/- 8.9
      mg/dl; P = 0.0025) than subjects with isolated fasting hyperglycemia (IFG/NGT).
      The relation of insulin resistance to glucose tolerance category was consistently
      seen in women and men and across the three ethnic groups of the IRAS (non
      Hispanic whites, African Americans, and Hispanics). Nondiabetic individuals with
      isolated postchallenge hyperglycemia (IGT) are more insulin resistant than
      individuals with isolated fasting hyperglycemia (IFG). The risk factor pattern
      (including increased insulin resistance) seen in isolated IGT identifies a
      subgroup of nondiabetic individuals who are likely to benefit from early
      intervention.

PMID- 15161761
TI  - Molecular alterations underlie nodal and paranodal degeneration in type 1
      diabetic neuropathy and are prevented by C-peptide.
AB  - To explore the molecular abnormalities underlying the degeneration of the node of
      Ranvier, a characteristic aberration of type 1 diabetic neuropathy, we examined
      in type 1 BB/Wor and type 2 BBZDR/Wor rats changes in expression of key molecules
      that make up the nodal and paranodal apparatus of peripheral nerve. Their
      posttranslational modifications were examined in vitro. Their responsiveness to
      restored insulin action was examined in type 1 animals replenished with
      proinsulin C-peptide. In sciatic nerve, the expression of contactin, receptor
      protein tyrosine phosphatase beta, and the Na(+)-channel beta(1) subunit,
      paranodal caspr and nodal ankyrin(G) was unaltered in 2-month type 1 diabetic
      BB/Wor rats but significantly decreased after 8 months of diabetes. These
      abnormalities were prevented by C-peptide administered to type 1 BB/Wor rats and
      did not occur in duration- and hyperglycemia-matched type 2 BBZDR/Wor rats. The
      expression of the alpha-Na(+)-channel subunit was unaltered. In SH-SY5Y cells,
      only the combination of insulin and C-peptide normalized posttranslational O
      linked N-acetylglucosamine modifications and maximized serine phosphorylation of
      ankyrin(G) and p85 binding to caspr. The beneficial effects of C-peptide resulted
      in significant normalization of the nerve conduction deficits. These data
      describe for the first time the progressive molecular aberrations underlying
      nodal and paranodal degenerative changes in type 1 diabetic neuropathy and
      demonstrate that they are preventable by insulinomimetic C-peptide.

PMID- 15161762
TI  - Early endothelial dysfunction severely impairs skin blood flow response to local
      pressure application in streptozotocin-induced diabetic mice.
AB  - Pressure-induced vasodilation (PIV) is a mechanism whereby skin blood flow
      increases in response to progressive locally applied pressure. Skin blood flow in
      response to applied pressure decreased early in diabetic patients as a result of
      vascular and/or neural impairment. This study was designed to determine the
      effect of vascular changes on PIV in 1-week streptozotocin-induced diabetic mice.
      We assessed cutaneous microvascular response to local increasing pressure
      application measured by laser Doppler flowmetry (LDF) and endothelium-dependent
      and -independent vasodilation by iontophoretic delivery of acetylcholine and
      sodium nitroprusside and sciatic motor nerve conduction velocity and morphometry.
      In control mice, LDF increased 34% from baseline to 0.2 kPa external pressure,
      showing PIV response. In contrast, diabetic mice had no LDF increase in response
      to progressive external pressure. Moreover, after iontophoretic delivery of
      acetylcholine, endothelium-dependent vasodilation was largely attenuated in
      diabetic mice (25%) compared with control mice (81%), whereas vasodilation to
      sodium nitroprusside was not different between groups. Nerve function as assessed
      by sciatic nerve conduction velocity and morphometry did not differ between
      groups. These findings suggest that endothelial impairment is sufficient to
      severely alter PIV response, which seems to be highly sensitive to endothelial
      nitric oxide levels. PIV suppression could favor diabetes complications such as
      diabetic foot ulcers.

PMID- 15161763
TI  - Association between mannose-binding lectin and vascular complications in type 1
      diabetes.
AB  - Complement activation and inflammation have been suggested in the pathogenesis of
      diabetic vascular lesions. We investigated serum mannose-binding lectin (MBL)
      levels and polymorphisms in the MBL gene in type 1 diabetic patients with and
      without diabetic nephropathy and associated macrovascular complications.
      Polymorphisms in the MBL gene and serum MBL levels were determined in 199 type 1
      diabetic patients with overt nephropathy and 192 type 1 diabetic patients with
      persistent normoalbuminuria matched for age, sex, and duration of diabetes, as
      well as in 100 healthy control subjects. The frequencies of high- and low
      expression MBL genotypes were similar in patients with type 1 diabetic and
      healthy control subjects. High MBL genotypes were significantly more frequent in
      diabetic patients with nephropathy than in the normoalbuminuric group, and the
      risk of having nephropathy given a high MBL genotype assessed by odds ratio (OR)
      was 1.52 (1.02-2.27, P = 0.04). Median serum MBL concentrations were
      significantly higher in patients with nephropathy than in patients with
      normoalbuminuria: 2,306 microg/l (interquartile range [IQR] 753-4,867 microg/l)
      vs. 1,491 microg/l (577-2,944 microg/l), P = 0.0003. In addition, even when
      comparing patients with identical genotypes, serum MBL levels were higher in the
      nephropathy group than in the normoalbuminuric group. Patients with a history of
      cardiovascular disease had significantly elevated MBL levels independent of
      nephropathy status (3,178 microg/l [IQR 636-5,231 microg/l] vs. 1,741 microg/l
      [656-3,149 microg/l], P = 0.02). The differences in MBL levels between patients
      with and without vascular complications were driven primarily by pronounced
      differences among carriers of high MBL genotypes (P < 0.0001). Our findings
      suggest that MBL may be involved in the pathogenesis of micro- and macrovascular
      complications in type 1 diabetes, and that determination of MBL status might be
      used to identify patients at increased risk of developing these complications.

PMID- 15161764
TI  - A new mouse model of type 2 diabetes, produced by N-ethyl-nitrosourea
      mutagenesis, is the result of a missense mutation in the glucokinase gene.
AB  - Here we report the first cloned N-ethyl-nitrosourea (ENU)-derived mouse model of
      diabetes. GENA348 was identified through free-fed plasma glucose measurement,
      being more than 2 SDs above the population mean of a cohort of >1,201 male ENU
      mutant mice. The underlying gene was mapped to the maturity-onset diabetes of the
      young (MODY2) homology region of mouse chromosome 11 (logarithm of odds 6.0).
      Positional candidate gene analyses revealed an A to T transversion mutation in
      exon 9 of the glucokinase gene, resulting in an isoleucine to phenylalanine
      change at amino acid 366 (I366F). Heterozygous mutants have 67% of the enzyme
      activity of wild-type littermates (P < 0.0012). Homozygous mutants have less
      enzyme activity (14% of wild-type activity) and are even less glucose tolerant.
      The GENA348 allele is novel because no mouse or human diabetes studies have
      described a mutation in the corresponding amino acid position. It is also the
      first glucokinase missense mutation reported in mice and is homozygous viable,
      unlike the global knockout mutations. This work demonstrates that ENU mutagenesis
      screens can be used to generate models of complex phenotypes, such as type 2
      diabetes, that are directly relevant to human disease.

PMID- 15161765
TI  - Interaction and association analysis of a type 1 diabetes susceptibility locus on
      chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families.
AB  - We have previously reported suggestive linkage to chromosome 5p13-q13 in type 1
      diabetic families. ISL1, a transcription factor involved in pancreas development,
      maps to this region. Sequencing of the ISL1 gene in patients and control subjects
      identified seven single nucleotide polymorphisms (SNPs) and one microsatellite in
      noncoding regions. Four haplotypes formed by six of these SNPs and one
      microsatellite were associated with type 1 diabetes in Swedish families (P <
      0.04). To identify possible interactions with the 5q11-q13 region, we applied
      pathway-restricted linkage analysis by analyzing for effects from regions
      encoding other transcription factors that are active during pancreas development
      and maintenance of insulin production. Linkage analysis allowing for interaction
      between 5q11-q13 and 7q32 resulted in an increase of logarithm of odds from 2.2
      to 5.3. This increase was estimated to correspond to a P value <0.0016 using
      permutation. The transcription factor PAX4 is located at 7q32 and participates
      downstream of ISL1 in the transcription factor cascade critical to beta-cell
      development. Association with type 1 diabetes was also observed using the
      transmission disequilibrium test for two haplotypes at the PAX4 locus (P < 0.05).
      We conclude that pathway-restricted linkage analysis assists in the
      identification of possible gene-gene interactions and that 5q11-q13 and 7q32
      together constitute a significant susceptibility factor for type 1 diabetes.

PMID- 15161766
TI  - A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a
      mutation in the human insulin receptor gene.
AB  - Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an
      autosomal-dominant inheritance have been etiologically characterized. In the
      present study, we have delineated the genetics and metabolic phenotype of a novel
      form of hypoglycemia in a large pedigree with an apparent autosomal-dominant
      transmission. After initial investigations of the proband, her mother, and a
      sister, the study was extended to 19 family members in three generations. Glucose
      tolerance was assessed by a 5-h oral glucose tolerance test (OGTT) and insulin
      sensitivity by euglycemic-hyperinsulinemic clamp in six affected family members
      and six control subjects. To identify the genetic cause of hypoglycemia, linkage
      analysis and mutation analysis of genomic DNA from all family members were
      performed. All affected family members were characterized by postprandial
      hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C
      peptide ratio. The 5-h OGTT demonstrated hyperinsulinemic hypoglycemia, and the
      clamp studies showed reduced insulin sensitivity and clearance of serum insulin
      in affected family members compared with control subjects. Linkage analysis and
      subsequent mutation screening revealed a missense mutation (Arg1174Gln) in the
      tyrosine kinase domain of the insulin receptor gene that cosegregated with the
      disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report
      a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The
      findings demonstrate the coexistence of severe postprandial hypoglycemia, insulin
      resistance, and impaired insulin clearance and suggest that hypoglycemia should
      be considered as a phenotype linked to heterozygote mutations in the insulin
      receptor gene.

PMID- 15161767
TI  - Diabetes-associated mutations in insulin identify invariant receptor contacts.
AB  - Mutations in human insulin cause an autosomal-dominant syndrome of diabetes and
      fasting hyperinsulinemia. We demonstrate by residue-specific photo cross-linking
      that diabetes-associated mutations occur at receptor-binding sites. The studies
      use para-azido-phenylalanine, introduced at five sites by total protein
      synthesis. Because two such sites (Val(A3) and Phe(B24)) are largely buried in
      crystal structures of the free hormone, their participation in receptor binding
      is likely to require a conformational change to expose a hidden functional
      surface. Our results demonstrate that this surface spans both chains of the
      insulin molecule and includes sites of rare human mutations that cause diabetes.

PMID- 15161768
TI  - Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis
      in response to regular exercise in nondiabetic individuals: the HERITAGE family
      study.
AB  - We recently reported that a genomic region close to the leptin locus was linked
      to fasting insulin response to exercise training in nondiabetic white subjects.
      We tested the hypothesis that common exonic variants in the leptin (LEP) and
      leptin receptor (LEPR) genes modify the effects of regular physical activity on
      glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In
      whites, exercise increased insulin sensitivity index (P = 0.041) and disposition
      index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K
      homozygotes, increased glucose disappearance index more in the R109R homozygotes
      than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only
      in the 109R allele carriers (P = 0.018). We also found an interaction between the
      LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites
      (P = 0.010). The association between the LEP A19G polymorphism and the change in
      insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in
      insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R
      allele. Similar interaction was observed in blacks (P = 0.046). Variations in the
      LEP and LEPR genes are associated with the magnitude of the effects of regular
      exercise on glucose homeostasis in nondiabetic individuals.

PMID- 15161769
TI  - Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation
      of a susceptibility locus on chromosome 1q21-q25.
AB  - We conducted an autosomal genome scan to map loci for type 2 diabetes in a Hong
      Kong Chinese population. We studied 64 families, segregating type 2 diabetes, of
      which 57 had at least one member with an age at diagnosis of </=40 years. These
      families included a total of 126 affected sibpairs and 4 other affected relative
      pairs. Nonparametric linkage analysis revealed seven regions showing nominal
      evidence for linkage with type 2 diabetes (logarithm of odds [LOD] >0.59,
      P(pointwise) < 0.05): chromosome 1 at 173.9 cM (LOD = 3.09), chromosome 3 at 26.3
      cM (LOD = 1.27), chromosome 4 at 135.3 cM (LOD = 2.63), chromosome 5 at 139.3 cM
      (LOD = 0.84), chromosome 6 at 178.9 cM (LOD = 1.91), chromosome 12 at 48.7 cM
      (LOD = 1.99), and chromosome 18 at 28.1 cM (LOD = 1.00). Simulation studies
      showed genome-wide significant evidence for linkage of the chromosome 1 region
      (P(genome-wide) = 0.036). We have confirmed the results of previous studies for
      the presence of a susceptibility locus on chromosome 1q21-q25 (173.9 cM) and
      suggest the locations of other loci that may contribute to the development of
      type 2 diabetes in Hong Kong Chinese.

PMID- 15161770
TI  - Lower within-subject variability of insulin detemir in comparison to NPH insulin
      and insulin glargine in people with type 1 diabetes.
AB  - The aim of this randomized double-blind study was to compare the within-subject
      variability of the glucose-lowering effect of a novel insulin analog, insulin
      detemir, with that of insulin glargine and NPH insulin in people with type 1
      diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean
      +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 +/- 9
      years) participated in this parallel group comparison. Each subject received four
      single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18),
      insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose
      clamp conditions (target blood glucose concentration 5.5 mmol/l) on four
      identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and
      pharmacokinetic (serum concentrations of insulin detemir, human insulin, and
      insulin glargine) properties of the basal insulin preparations were recorded for
      24 h postdosing. Insulin detemir was associated with significantly less within
      subject variability than both NPH insulin and insulin glargine, as assessed by
      the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR
      AUC((0-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h))
      27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons].
      Insulin detemir also provided less within-subject variability in the
      pharmacokinetic end points: maximal concentration (C(max)) 18 vs. 24 vs. 34%; INS
      AUC((0- infinity )) 14 vs. 28 vs. 33%. The results suggest that insulin detemir
      has a significantly more predictable glucose-lowering effect than both NPH
      insulin and insulin glargine.

PMID- 15161771
TI  - Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2
      diabetes.
AB  - Whereas thiazolidinediones (TZDs) are known to rapidly improve insulin action in
      animals, short durations of TZD therapy have never been studied in humans. Among
      the many known actions of TZDs, increased circulating levels of the high
      molecular weight (HMW) multimer of adiponectin may be an important insulin
      sensitizing mechanism. We examined the effects of only 21 days of 45 mg of
      pioglitazone (P+) versus placebo (P-) in nine subjects with type 2 diabetes
      (HbA(1c), 10.9 +/- 0.6%; BMI, 31.9 +/- 1.5 kg/m(2)). Total adiponectin levels
      increased by approximately twofold in P+ in association with increased adipose
      tissue gene expression. However, plasma free fatty acid and glucose levels were
      unchanged, and there were only minimal changes in other "adipokines." Glucose
      fluxes ([3-(3)H]glucose infusion) were measured during 6-h euglycemic (5 mmol/l)
      "pancreatic clamp" studies (somatostatin/glucagon/growth hormone) with stepped
      insulin levels. Pioglitazone induced marked decreases in endogenous glucose
      production (P+ = 0.9 +/- 0.1 vs. P- = 1.7 +/- 0.3 mg. kg(-1). min(-1); P < 0.05)
      at physiologic hyperinsulinemia ( approximately 50 microU/ml), which was highly
      correlated with an increased ratio of HMW adiponectin/total levels (r(2) = 0.90).
      Maximal insulin stimulation ( approximately 400 microU/ml) revealed pioglitazone
      associated increases in glucose uptake (P+ = 10.5 +/- 0.9 vs. P- = 8.9 +/- 0.8
      mg. kg(-1). min(-1); P < 0.05), which did not correlate with HMW or total
      adiponectin levels. Thus, only 21 days of pioglitazone therapy improved insulin
      action in humans with type 2 diabetes. Increased abundance of the HMW adiponectin
      multimer may contribute to the hepatic insulin-sensitizing effects of these
      agents.

PMID- 15161772
TI  - Biological variation in HbA1c predicts risk of retinopathy and nephropathy in
      type 1 diabetes.
AB  - OBJECTIVE: We hypothesized that biological variation in HbA(1c), distinct from
      variation attributable to mean blood glucose (MBG), would predict risk for
      microvascular complications in the Diabetes Control and Complications Trial
      (DCCT). RESEARCH DESIGN AND METHODS: A longitudinal multiple regression model was
      developed from MBG and HbA(1c) measured in the 1,441 DCCT participants at
      quarterly visits. A hemoglobin glycation index (HGI = observed HbA(1c) -
      predicted HbA(1c)) was calculated for each visit to assess biological variation
      based on the directional deviation of observed HbA(1c) from that predicted by MBG
      in the model. The population was subdivided by thirds into high-, moderate-, and
      low-HGI groups based on mean participant HGI during the study. Cox proportional
      hazard analysis compared risk for development or progression of retinopathy and
      nephropathy between HGI groups controlled for MBG, age, treatment group, strata,
      and duration of diabetes. RESULTS: Likelihood ratio and t tests on HGI rejected
      the assumption that HbA(1c) levels were determined by MBG alone. At 7 years'
      follow-up, patients in the high-HGI group (higher-than-predicted HbA(1c)) had
      three times greater risk of retinopathy (30 vs. 9%, P < 0.001) and six times
      greater risk of nephropathy (6 vs. 1%, P < 0.001) compared with the low-HGI
      group. CONCLUSIONS: Between-individual biological variation in HbA(1c), which is
      distinct from that attributable to MBG, was evident among type 1 diabetic
      patients in the DCCT and was a strong predictor of risk for diabetes
      complications. Identification of the processes responsible for biological
      variation in HbA(1c) could lead to novel therapies to augment treatments directed
      at lowering blood glucose levels and preventing diabetes complications.

PMID- 15161773
TI  - Repaglinide versus nateglinide monotherapy: a randomized, multicenter study.
AB  - OBJECTIVE: A randomized, parallel-group, open-label, multicenter 16-week clinical
      trial compared efficacy and safety of repaglinide monotherapy and nateglinide
      monotherapy in type 2 diabetic patients previously treated with diet and
      exercise. RESEARCH DESIGN AND METHODS: Enrolled patients (n = 150) had received
      treatment with diet and exercise in the previous 3 months with HbA(1c) >7 and <
      or =12%. Patients were randomized to receive monotherapy with repaglinide (n =
      76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal,
      maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points
      were changes in HbA(1c) and fasting plasma glucose (FPG) values from baseline,
      respectively. Postprandial glucose, insulin, and glucagon were assessed after a
      liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse
      events or hypoglycemia. RESULTS: Mean baseline HbA(1c) values were similar in
      both groups (8.9%). Final HbA(1c) values were lower for repaglinide monotherapy
      than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA(1c)
      were significantly greater for repaglinide monotherapy than nateglinide
      monotherapy (-1.57 vs. -1.04%; P = 0.002). Mean changes in FPG also demonstrated
      significantly greater efficacy for repaglinide than nateglinide (-57 vs. -18
      mg/dl; P < 0.001). HbA(1c) values <7% were achieved by 54% of repaglinide-treated
      patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for
      repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated
      with repaglinide (five subjects with one episode each) who had minor hypoglycemic
      episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight
      gain at the end of the study was 1.8 kg in the repaglinide group as compared with
      0.7 kg for the nateglinide group. CONCLUSIONS: In patients previously treated
      with diet and exercise, repaglinide and nateglinide had similar postprandial
      glycemic effects, but repaglinide monotherapy was significantly more effective
      than nateglinide monotherapy in reducing HbA(1c) and FPG values after 16 weeks of
      therapy.

PMID- 15161774
TI  - Development of a diabetes diet-related quality-of-life scale.
AB  - OBJECTIVE: The purpose of this study was to assess the reliability and validity
      of the Diabetes Diet-Related Quality-of-Life (DDRQOL) scale, which is a measure
      of the influence of diet therapy on patients' quality of life (QOL). RESEARCH
      DESIGN AND METHODS: Patients with type 2 diabetes (n = 236) who were being
      treated on an outpatient basis were asked to complete the self-administered
      DDRQOL instrument. The factor validity, convergent and discriminant validity,
      internal consistency, and reproducibility of the DDRQOL scale were then assessed.
      Spearman's rank correlation coefficients among the DDRQOL scale and each of the
      SF-36 subscale scores were calculated to evaluate its convergent and discriminant
      validity. RESULTS: Based on the results of the factor analysis, the following
      seven subscales were adopted for the DDRQOL: "satisfaction with diet," "burden of
      diet therapy," "perceived merits of diet therapy," "general perception of diet,"
      "restriction of social functions," "vitality," and "mental health." As
      hypothesized, the DDRQOL scale was associated with each of the SF-36 subscales,
      with convergent and discriminant validity being generally exhibited. Cronbach's
      alpha-coefficient was between 0.71 and 0.84, suggesting strong internal
      consistency. The intraclass correlation coefficient of the subscales, with the
      results of a test-retest conducted 2 weeks later, was between 0.46 and 0.75,
      suggesting some degree of reproducibility. CONCLUSIONS: These findings indicate
      that the DDRQOL scale has a reasonable degree of reliability and validity, and
      its application for the assessment of the needs of a patient's diet and the
      evaluation of diet education with regard to QOL is awaited.

PMID- 15161776
TI  - High-fiber cereal reduces postprandial insulin responses in hyperinsulinemic but
      not normoinsulinemic subjects.
AB  - OBJECTIVE: The objective of this study was to compare the plasma glucose and
      insulin responses elicited by two ready-to-eat breakfast cereals (one being high
      and the other being low in cereal fiber) and to see if the differences in
      response depended on subjects' fasting plasma insulin. RESEARCH DESIGN AND
      METHODS: Nondiabetic men (n = 77) were studied on two occasions after 10- to 14-h
      overnight fasts. They consumed 25 g of available carbohydrate from high- or low
      fiber breakfast cereals in random order with blood taken at intervals for 2 h.
      Data from the 42 men with high fasting plasma insulin (FPI) on screening (>40
      pmol/l) were compared with those from the 35 men with normal FPI (< or =40
      pmol/l). RESULTS: Hyperinsulinemic men had significantly higher waist
      circumference and BMI, lower HDL cholesterol, and a trend toward higher
      triglycerides (P = 0.07) than control subjects. In all 77 subjects, the
      incremental area under the glucose response curve (AUC) after high-fiber cereal
      was 11.8 +/- 5.5% (P = 0.036) less than after low-fiber cereal with the
      reductions being equivalent in the hyperinsulinemic (12.6 +/- 8.3%) and control
      (10.9 +/- 9.1%) groups. However, insulin peak rise was reduced by the high-fiber
      cereal only in hyperinsulinemic men (351 +/- 29 vs. 485 +/- 55 pmol/l) but not in
      control subjects (211 +/- 20 vs. 220 +/- 20 pmol/l; cereal x group interaction P
      = 0.044). Insulin AUC after the high-fiber cereal, expressed as a percentage of
      that after low-fiber cereal, was negatively related to FPI (P = 0.009) but not to
      age, BMI, or waist circumference. CONCLUSIONS: The high-fiber cereal reduced
      glucose responses to the same extent in normal and hyperinsulinemic men, but
      reduced insulin responses only in hyperinsulinemic subjects.

PMID- 15161775
TI  - Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet
      therapy in type 2 diabetic patients.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of apolipoprotein
      (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet
      therapy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-four
      diabetic patients with the apoE3/3 genotype and 11 diabetic patients with the
      apoE4/3 genotype were recruited. Participants were hospitalized for calorie
      restricted diet therapy (25.0 kcal. kg body wt(-1). day(-1)) for 14 days. Body
      weight, fasting plasma glucose (FPG) levels, and plasma lipid levels on hospital
      days 1 and 14 were compared between the two apoE genotype groups. RESULTS: There
      were no significant differences in baseline FPG levels, HbA(1c) levels, BMI, and
      plasma levels of total cholesterol, triglyceride, and HDL cholesterol between the
      two apoE genotype groups, but baseline plasma levels of LDL cholesterol were
      significantly higher in the apoE4/3 group than in the apoE3/3 group. Body weight
      decreased slightly and FPG levels decreased significantly after diet therapy in
      both apoE genotype groups. In the apoE3/3 group, only plasma levels of
      triglyceride decreased significantly after diet therapy, whereas in the apoE4/3
      group, plasma levels of triglyceride, total cholesterol, and LDL cholesterol
      decreased significantly after diet therapy. The decrease (percentage of change)
      in total cholesterol (-16.3 vs. -6.6%) and LDL cholesterol (-15.6 vs. -0.7%)
      after diet therapy was significantly greater in the apoE4/3 group than in the
      apoE3/3 group. CONCLUSIONS: Calorie-restricted diet therapy is more effective in
      reducing plasma LDL cholesterol in type 2 diabetic patients with the apoE4
      allele.

PMID- 15161777
TI  - Relation of lower-extremity amputation to all-cause and cardiovascular disease
      mortality in American Indians: the Strong Heart Study.
AB  - OBJECTIVE: To compare risk of all-cause and cardiovascular disease (CVD)
      mortality in people with a lower-extremity amputation (LEA) attributable to
      diabetes and people without an LEA. RESEARCH DESIGN AND METHODS: The Strong Heart
      Study is a study of CVD and its risk factors in 13 American-Indian communities.
      LEA was ascertained at baseline by direct examination of the legs and feet.
      Mortality surveillance is complete through 2000. RESULTS: Of 2,108 participants
      with diabetes at baseline, 134 participants (6.4%) had an LEA. Abnormal ankle
      brachial index (53%), albuminuria (87%), and long diabetes duration (mean 19.8
      years) were common among diabetic subjects with LEA. Mean diabetes duration among
      diabetic participants without LEA and in those with toe and below-the-knee
      amputations was 11.9, 18.6, and 21.1 years, respectively. During 8.7 (+/-2.9)
      years of follow-up, 102 of the participants with LEA (76%) died from all causes
      and 35 (26%) died from CVD. Of the 1,974 diabetic participants without LEA at
      baseline, 604 (31%) died from all causes and 206 (10%) died from CVD. The
      unadjusted hazard ratios (HRs) for all-cause and CVD mortality in diabetic
      participants with LEA compared with those without were 4.0 and 4.1, respectively.
      Adjusting for known and suspected confounders, LEA persisted as a predictor of
      all-cause (HR 2.2, 95% CI 1.7-2.9) and CVD mortality (HR 1.9, 95% CI 1.3-2.9). We
      observed a significant interaction between baseline LEA and sex on CVD mortality,
      with female sex conferring added risk of CVD mortality. CONCLUSIONS: LEA is a
      potent predictor of all-cause and CVD mortality in diabetic American Indians. The
      combination of female sex and LEA is associated with greater risk of CVD
      mortality than either factor alone.

PMID- 15161778
TI  - Younger age at onset and sex predict celiac disease in children and adolescents
      with type 1 diabetes: an Italian multicenter study.
AB  - OBJECTIVE: To estimate the prevalence of biopsy-confirmed celiac disease in
      Italian children and adolescents with type 1 diabetes and to assess whether age
      at onset of type 1 diabetes is independently associated with diagnosis of celiac
      disease. RESEARCH DESIGN AND METHODS: The study group was a clinic-based cohort
      of children and adolescents with type 1 diabetes cared for in 25 Italian centers
      for childhood diabetes. Yearly screening for celiac disease was performed using
      IgA/IgG anti-gliadin and IgA anti-endomysium antibodies. RESULTS: Of the 4,322
      children and adolescents (age 11.8 +/- 4.2 years) identified with type 1
      diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%,
      95% confidence interval [CI] 6.0-7.6), with a higher risk seen in girls than in
      boys (odds ratio [OR] 1.93, 1.51-2.47). In 89% of these, diabetes was diagnosed
      before celiac disease. In logistic regression analyses, being younger at onset of
      diabetes, being female, and having a diagnosis of a thyroid disorder were
      independently associated with the risk of having diabetes and celiac disease. In
      comparison with subjects who were older than 9 years at onset of diabetes,
      subjects who were younger than 4 years at onset had an OR of 3.27 (2.20-4.85).
      CONCLUSIONS: We have provided evidence that 1) the prevalence of biopsy-confirmed
      celiac disease in children and adolescents with type 1 diabetes is high (6.8%);
      2) the risk of having both diseases is threefold higher in children diagnosed
      with type 1 diabetes at age <4 years than in those age >9 years; and 3) girls
      have a higher risk of having both diseases than boys.

PMID- 15161779
TI  - Mortality and predictors of mortality in a cohort of Brazilian type 2 diabetic
      patients.
AB  - OBJECTIVE: To investigate mortality rates and predictors of mortality in
      Brazilian type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A prospective
      follow-up study was carried out with 471 type 2 diabetic outpatients. Primary end
      points were all-cause, diabetes-related, and cardiovascular deaths. Excess
      mortality in this cohort was evaluated by calculating standardized mortality
      ratios (SMRs) in relation to those of the Rio de Janeiro population. Predictors
      of mortality were assessed by Kaplan-Meier survival curves and by uni- and
      multivariate Cox survival analyses. RESULTS: During a median follow-up of 57
      months (range 2-84 months), 121 (25.7%) patients died, 91 (75.2%) from diabetes
      related causes and 44 (36.4%) from cardiovascular diseases. After adjusting for
      age and sex, the all-cause SMR was 3.36 (95% confidence interval [CI] 2.81-4.02)
      and the cardiovascular SMR was 3.28 (CI 2.44-4.41). In the Cox multivariate
      analysis, the predictors of mortality were older age, increased 24-h proteinuria,
      preexisting vascular disease, presence of frequent ventricular premature
      contractions and prolonged maximum heart rate-corrected QT interval on baseline
      electrocardiogram, and decreased serum HDL cholesterol. The use of beta-blockers
      was a protective factor. In Kaplan-Meier curves, these variables were capable of
      distinguishing subgroups of patients with significantly different prognoses.
      CONCLUSIONS: Brazilian type 2 diabetic patients had a more than threefold excess
      mortality than the general population, largely because of increased
      cardiovascular mortality risk. Several clinical, laboratory, and
      electrocardiographic predictors of mortality were identified that could possibly
      be modified to decrease the mortality burden of type 2 diabetes in Brazil.

PMID- 15161780
TI  - Improvements in patient-reported outcomes associated with an intervention to
      enhance quality of care for rural patients with type 2 diabetes: results of a
      controlled trial.
AB  - OBJECTIVE: The aim of this study was to examine patient-reported outcomes in a
      controlled trial of a multifaceted provider-level intervention to improve quality
      of care for rural patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We
      conducted a before/after intervention study with concurrent controls in two rural
      regions in Alberta, Canada. The intervention consisted of six monthly visits by a
      multidisciplinary health care team and was primarily directed at primary care
      providers. Clinical and patient-reported outcomes were assessed after 6 months.
      Patient-reported outcomes included changes in health-related quality of life
      (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle
      (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of
      covariance was used to assess differences over time between the control and
      intervention regions. RESULTS: A total of 200 intervention and 172 control
      subjects were included in this analysis. After adjusting for important clinical
      and demographic differences, a statistically significant and clinically important
      improvement in the overall HUI3 score was seen at the 6-month follow-up in the
      intervention region (0.06 [95% CI 0.02-0.10]) compared with the control region
      (0.01 [-0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction
      with general medical care (P < 0.001 between groups) and diabetes care (P < 0.001
      between groups) increased among patients in the intervention region compared with
      the control region. Self-efficacy, attitudes, and beliefs about diabetes control
      all increased in the intervention region when compared with the control region,
      but adherence to self-care activities did not. CONCLUSIONS: A provider-level
      intervention directed at improving quality of clinical care for patients with
      type 2 diabetes also had a favorable impact on overall health-related quality of
      life, satisfaction with care, and other humanistic outcomes.

PMID- 15161781
TI  - The coping styles of adolescents with type 1 diabetes are associated with degree
      of metabolic control.
AB  - OBJECTIVE: To systematically study the various coping styles in a population
      based sample of adolescents with type 1 diabetes, exploring the association of
      different coping styles with metabolic control and adolescent self-reported
      diabetes-related quality of life. RESEARCH DESIGN AND METHODS: Of a total
      population of 116 adolescents with type 1 diabetes (age 13-18 years), 103 (89%)
      participated in the study, completing a questionnaire to obtain information on
      coping styles and perception of diabetes-specific quality of life. The mean age
      (+/-SD) was 14.9 +/- 1.6 years, diabetes duration 7.1 +/- 3.8 years, HbA(1c) 9.4
      +/- 1.6%, and male-to-female ratio 52:51. RESULTS: There was a significant
      correlation between higher HbA(1c) values and higher degree of mental (r = 0.25,
      P < 0.05) and behavioral (r = 0.33, P < 0.01) disengagement and aggressive coping
      (r = 0.33, P < 0.01). Stepwise multiple regression analyses indicated that
      greater use of aggressive coping (P < 0.05) and behavioral disengagement (P <
      0.05) were significantly related to increase in HbA(1c). Greater use of active
      coping (P < 0.05) was significantly related to a decrease in HbA(1c). Partial
      correlation analysis showed that lower scores on diabetes-specific quality of
      life were significantly related to greater use of emotion-focused coping (r = 
      0.22 to -0.49). Stepwise multiple regression analyses showed that greater use of
      mental disengagement was significantly related to lower degree of perceived
      diabetes-related impact. CONCLUSIONS: Poor metabolic control and lower degree of
      diabetes-related quality of life are associated with greater use of emotion
      focused coping in adolescents with type 1 diabetes.

PMID- 15161782
TI  - Patient satisfaction and glycemic control after 1 year with inhaled insulin
      (Exubera) in patients with type 1 or type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to determine patient satisfaction in
      patients with type 1 or type 2 diabetes receiving an inhaled insulin or
      subcutaneous insulin regimen, as assessed by pooled analysis of two 12-week
      parent studies and 1-year extension studies. RESEARCH DESIGN AND METHODS: In the
      12-week parent studies, patients with type 1 (n = 70) or type 2 (n = 51) diabetes
      were randomized to an inhaled insulin or subcutaneous insulin regimen. In the 1
      year extension studies, patients were allowed to select either treatment regimen.
      Patient satisfaction was assessed at baseline, week 12, and 1 year using the
      Patient Satisfaction with Insulin Therapy questionnaire. RESULTS: Of the 60
      patients who received inhaled insulin during the parent studies, 85.0% (n = 51)
      chose to continue treatment, 13.3% (n = 8) switched to subcutaneous insulin, and
      1.7% (n = 1) did not continue. Of the 61 patients who received subcutaneous
      insulin, 21.3% (n = 13) chose to continue treatment, 75.4% (n = 46) switched to
      inhaled insulin, and 3.3% (n = 2) did not continue. From baseline (parent
      studies) to 1 year (extension studies), HbA(1c) reductions of 0.8% were
      sustained, and greater improvements were observed in the inhaled insulin group
      compared with the subcutaneous insulin group in terms of overall satisfaction
      (37.9 vs. 3.1%; P < 0.01) and ease of use (43.2 vs. -0.9%; P < 0.01).
      CONCLUSIONS: Inhaled insulin was preferred over subcutaneous insulin, which
      resulted in greater patient satisfaction up to 1 year in patients with type 1 or
      type 2 diabetes with durable effects on HbA(1c) levels.

PMID- 15161783
TI  - Ragaglitazar improves glycemic control and lipid profile in type 2 diabetic
      subjects: a 12-week, double-blind, placebo-controlled dose-ranging study with an
      open pioglitazone arm.
AB  - OBJECTIVE: Ragaglitazar is a novel insulin sensitizer with dual peroxisome
      proliferator-activated receptor (PPAR)-gamma and PPAR-alpha stimulating
      activities that improve plasma glucose and lipid profiles. The aim of the present
      dose-ranging study was to assess the efficacy and safety of ragaglitazar in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study included
      177 hypertriglyceridemic type 2 diabetic subjects who participated in a 12-week,
      double-blind, parallel, randomized, placebo-controlled dose-ranging study (open
      pioglitazone arm). Subjects received ragaglitazar (0.1, 1, 4, or 10 mg), placebo,
      or pioglitazone (45 mg). Efficacy parameters included fasting plasma levels of
      triglycerides and glucose (FPG) along with other lipid levels, A1C, and insulin.
      RESULTS: Ragaglitazar in doses of 1, 4, and 10 mg resulted in a significant
      decrease from baseline as compared with placebo in FPG (-48, -74, -77 mg/dl) and
      triglycerides (-40, -62, -51%), free fatty acids (-36, -54, -62%), apolipoprotein
      B (-13, -29, -25%), LDL cholesterol (-14 and -19% for 4- and 10-mg groups), and
      total cholesterol (-16 and -15% for 4 and 10 mg) and a significant increase in
      HDL cholesterol (20 and 31% for 1- and 4-mg groups, respectively). Changes in
      triglycerides and FPG for pioglitazone treatment were similar to 1 mg
      ragaglitazar. Mean A1C values of the 1-, 4-, and 10-mg ragaglitazar and
      pioglitazone groups were significantly reduced compared with placebo (-0.5, -1.3,
      -1.1, and -0.3%, respectively). Common adverse events were edema, weight
      increase, leukopenia, and anemia. CONCLUSIONS: Ragaglitazar provided glycemic
      control that was comparable with that of pioglitazone and, compared with placebo,
      provided significant improvement in the lipid profile.

PMID- 15161784
TI  - Reduced mortality associated with the use of ACE inhibitors in patients with type
      2 diabetes.
AB  - OBJECTIVE: ACE inhibitor therapy is widely used in lower-risk patients with type
      2 diabetes to reduce mortality, despite limited evidence to support this clinical
      strategy. The aim of this study was to evaluate the association between ACE
      inhibitor use and mortality in patients with diabetes and no cardiovascular
      disease. RESEARCH DESIGN AND SETTINGS: Using the Saskatchewan health databases,
      12,272 new users of oral hypoglycemic agents were identified between the years of
      1991 and 1996. We excluded 3,202 subjects with previous cardiovascular disease.
      Of the remaining subjects, 1,187 "new users" of ACE inhibitors were identified
      (ACE inhibitor cohort). Subjects not receiving ACE inhibitor therapy throughout
      the follow-up period served as the control cohort (n = 4,989). Subjects were
      prospectively followed until death or the end of 1999. Multivariate Cox
      proportional hazards models were used to assess differences in all-cause and
      cardiovascular-related mortality between cohort groups. RESULTS: Subjects were
      60.7 +/- 13.7 years old, 43.6% female, and were followed for an average of 5.3 +/
      2.1 years. Mean duration of ACE inhibitor therapy was 3.6 +/- 1.8 years. We
      observed significantly fewer deaths in the ACE inhibitor group (102 [8.6%])
      compared with the control cohort (853 [17.1%]), with an adjusted hazard ratio
      (HR) and 95% CI of 0.49 (0.40-0.61) (P < 0.001). Cardiovascular-related mortality
      was also reduced (40 [3.4%] vs. 261 [5.2%], adjusted HR, 0.63 [0.44-0.90]; P =
      0.012). CONCLUSIONS: The use of ACE inhibitors was associated with a significant
      reduction in all-cause and cardiovascular-related mortality in a broad spectrum
      of patients with type 2 diabetes and no cardiovascular disease.

PMID- 15161785
TI  - Improved glycemic control with no weight increase in patients with type 2
      diabetes after once-daily treatment with the long-acting glucagon-like peptide 1
      analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled
      trial.
AB  - OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed
      for once daily injection. This study assessed the efficacy and safety of
      liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH
      DESIGN AND METHODS: A double-blind, randomized, parallel-group, placebo
      controlled trial with an open-label comparator arm was conducted among 193
      outpatients with type 2 diabetes. The mean age was 56.6 years and the mean
      HbA(1c) was 7.6% across the treatment groups. Patients were randomly assigned to
      one of five fixed-dosage groups of liraglutide (0.045, 0.225, 0.45, 0.60, or 0.75
      mg), placebo, or open-label sulfonylurea (glimepiride, 1-4 mg). The primary end
      point was HbA(1c) after 12 weeks; secondary end points were fasting serum
      glucose, fasting C-peptide, fasting glucagon, fasting insulin, beta-cell
      function, body weight, adverse events, and hypoglycemic episodes. RESULTS: A
      total of 190 patients were included in the intention-to-treat (ITT) analysis.
      HbA(1c) decreased in all but the lowest liraglutide dosage group. In the 0.75-mg
      liraglutide group, HbA(1c) decreased by 0.75 percentage points (P < 0.0001) and
      fasting glucose decreased by 1.8 mmol/l (P = 0.0003) compared with placebo.
      Improvement in glycemic control was evident after 1 week. Body weight decreased
      by 1.2 kg in the 0.45-mg liraglutide group (P = 0.0184) compared with placebo.
      The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group (
      0.18; P = 0.0244) compared with placebo. Patients treated with glimepiride had
      decreased HbA(1c) and fasting glucose, but slightly increased body weight. No
      safety issues were raised for liraglutide; observed adverse events were mild and
      transient. CONCLUSIONS: A once-daily dose of liraglutide provides efficacious
      glycemic control and is not associated with weight gain. Adverse events with the
      drug are mild and transient, and the risk of hypoglycemia is negligible.

PMID- 15161786
TI  - Comparative roles of microvascular and nerve function in foot ulceration in type
      2 diabetes.
AB  - OBJECTIVE: To determine the relative roles of different modalities of sensory
      nerve function (large and small fiber) and the role of microvascular dysfunction
      in foot ulceration in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A
      total of 20 control subjects and 18 type 2 diabetic subjects with foot ulceration
      and 20 without were studied. None of the subjects had clinical features of
      peripheral vascular disease. The Computer-Aided Sensory Evaluator IV (CASE IV)
      was used to determine vibration detection threshold (VDT), cold detection
      threshold (CDT), warm detection threshold (WDT), and heat pain onset threshold
      (HPO). Vibration perception threshold (VPT) was also assessed by a
      neurothesiometer. Microvascular function (maximum hyperemia to skin heating to 44
      degrees C) was assessed using laser Doppler flowmetry (mean maximum hyperemia
      using laser Doppler flowmeter [LDF(max)]), laser Doppler imaging (mean maximum
      hyperemia using laser Doppler imager [LDI(max)]), and skin oxygenation with
      transcutaneous oxygen tension (TcpO(2)). RESULTS: VPT, VDT, CDT, and HPO were all
      significantly higher in individuals with ulceration than in those without (VPT
      and VDT: P < 0.0001) (CDT and HPO: P = 0.01). LDF(max), LDI(max), and TcpO(2)
      were significantly lower in the two diabetic groups than in the control subjects,
      but there was no difference between individuals with and without ulceration.
      Univariate logistic regression analysis revealed similar odds ratios for foot
      ulceration for VDT, CDT, HPO, and VPT (OR 1.97 [95% CI 1.30-2.98], 1.58 [1.20
      2.08], 2.30 [1.21-4.37], and 1.24 [1.08-1.42], respectively). None of the
      microvascular parameters yielded significant odds ratios for ulceration.
      CONCLUSIONS: This study found that there was no additional value in measuring
      small-fiber function with the CASE IV over measuring vibration by either CASE IV
      or the inexpensive neurothesiometer in discriminating between individuals with
      and without ulceration. Furthermore, none of the tests of microvascular function
      including the TcpO(2) were able to discriminate between individuals with and
      without ulceration, suggesting that such tests may not be of benefit in
      identifying subjects at greater risk of foot ulceration.

PMID- 15161787
TI  - Vascular effects of improving metabolic control with metformin or rosiglitazone
      in type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to test whether vascular reactivity is
      modified by improving metabolic control and peripheral insulin resistance in type
      2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized, double-blind design, we
      assigned 74 type 2 diabetic patients to rosiglitazone (8 mg/day), metformin
      (1,500 mg/day), or placebo treatment for 16 weeks and measured insulin
      sensitivity (euglycemic insulin clamp), ambulatory blood pressure, and forearm
      blood flow response to 1) intra-arterial acetylcholine (ACh), 2) intra-arterial
      nitroprusside, 3) the clamp, and 4) blockade of nitric oxide (NO) synthase.
      RESULTS: Compared with 25 nondiabetic subjects, patients had reduced insulin
      sensitivity (30 +/- 1 vs. 41 +/- 3 micromol. min(-1). kg fat-free mass(-1); P <
      0.001) and reduced maximal response to ACh (586 +/- 42 vs. 883 +/- 81%; P <
      0.001). Relative to placebo, 16 weeks of rosiglitazone and metformin similarly
      reduced fasting glucose (-2.3 +/- 0.5 and -2.3 +/- 0.5 mmol/l) and HbA(1c) (-1.2
      +/- 0.3 and -1.6 +/- 0.3%). Insulin sensitivity increased with rosiglitazone (+6
      +/- 3 micromol. min(-1). kg fat-free mass(-1); P < 0.01) but not with metformin
      or placebo. Ambulatory diastolic blood pressure fell consistently (-2 +/- 1 mmHg;
      P < 0.05) only in the rosiglitazone group. Nitroprusside dose response, clamp
      induced vasodilatation, and NO blockade were not affected by either treatment. In
      contrast, the slope of the ACh dose response improved with rosiglitazone (+40%
      versus baseline, P < 0.05, +70% versus placebo, P < 0.005) but did not change
      with either metformin or placebo. This improvement in endothelium-dependent
      vasodilatation was accompanied by decrements in circulating levels of free fatty
      acids and tumor necrosis factor-alpha. CONCLUSIONS: At equivalent glycemic
      control, rosiglitazone, but not metformin, improves endothelium dependent
      vasodilatation and insulin sensitivity in type 2 diabetes.

PMID- 15161788
TI  - Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing
      lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma
      triglycerides.
AB  - OBJECTIVE: Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and
      of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of
      triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme
      lipoprotein lipase (LPL) and by interference with lipoprotein binding to cell
      surface receptors. Elevated plasma LpB:C-III is an independent risk factor for
      cardiovascular disease. We studied the effect of atorvastatin on plasma LpB:C-III
      and HDL apoC-III. RESEARCH DESIGN AND METHODS: We studied the effect of 30 weeks'
      treatment with 10 and 80 mg atorvastatin on plasma apoC-III levels in a
      randomized, double-blind, placebo-controlled trial involving 217 patients with
      type 2 diabetes and fasting plasma triglycerides between 1.5 and 6.0 mmol/l.
      RESULTS: Baseline levels of total plasma apoC-III, HDL apoC-III, and LpB:C-III
      were 41.5 +/- 10.0, 17.7 +/- 5.5, and 23.8 +/- 7.7 mg/l, respectively. Plasma
      apoC-III was strongly correlated with plasma triglycerides (r = 0.74, P < 0.001).
      Atorvastatin 10- and 80-mg treatment significantly decreased plasma apoC-III
      (atorvastatin 10 mg, 21%, and 80 mg, 27%), HDL apoC-III (atorvastatin 10 mg, 22%,
      and 80 mg, 28%) and LpB:C-III (atorvastatin 10 mg, 23%, and 80 mg, 28%; all P <
      0.001). The decrease in plasma apoC-III, mainly in LpB:C-III, strongly correlated
      with a decrease in triglycerides (atorvastatin 10 mg, r = 0.70, and 80 mg, r =
      0.78; P < 0.001). Atorvastatin treatment also leads to a reduction in the HDL
      apoC-III-to-HDL cholesterol and HDL apoC-III-to-apoA-I ratios, indicating a
      change in the number of apoC-III per HDL particle (atorvastatin 10 mg, -21%, and
      80 mg, -31%; P < 0.001). CONCLUSIONS: Atorvastatin treatment resulted in a
      significant dose-dependent reduction in plasma apoC-III, HDL apoC-III, and LpB:C
      III levels in patients with type 2 diabetes. These data indicate a potentially
      important antiatherogenic effect of statin treatment and may explain (part of)
      the triglyceride-lowering effect of atorvastatin.

PMID- 15161789
TI  - Changes in insulin sensitivity in response to troglitazone do not differ between
      subjects with and without the common, functional Pro12Ala peroxisome proliferator
      activated receptor-gamma2 gene variant: results from the Troglitazone in
      Prevention of Diabetes (TRIPOD) study.
AB  - OBJECTIVE: We have tested whether the Pro12Ala variant of the peroxisome
      proliferator-activated receptor (PPAR)-gamma nuclear receptor involved in
      thiazolidinedione (TZD) action accounted for the failure of troglitazone to
      increase insulin sensitivity in nondiabetic Hispanic women with previous
      gestational diabetes treated in the Troglitazone in Prevention of Diabetes
      (TRIPOD) study. RESEARCH DESIGN AND METHODS: Ninety-three women assigned to
      troglitazone had intravenous glucose tolerance tests at randomization and after 3
      months of treatment with troglitazone, 400 mg/day, and were genotyped for the
      Pro12Ala variant of the PPAR-gamma gene. Subjects were divided into tertiles
      based on their change in minimal model insulin sensitivity (S(i)) during the
      first 3 months of troglitazone treatment. RESULTS: The mean changes in S(i) in
      the bottom, middle, and top tertiles of S(i) response were -0.21 +/- 0.57, 0.91
      +/- 0.26, and 2.58 +/- 1.32 min(-1) per microU/ml. 10(-4), respectively.
      Frequencies of the Ala/- genotype were 30, 22, and 26% in the same three tertiles
      (P = 0.77). Analysis of phenotypes by genotype revealed only small differences
      between the Pro/Pro and Ala/- groups, respectively, in baseline S(i) (2.76 +/-
      0.19 vs. 2.33 +/- 0.33 x 10(-4) min(-1) per microU/ml; P = 0.27), the change in
      S(i) after 3 months of troglitazone treatment (1.19 +/- 0.17 vs. 0.93 +/- 0.30; P
      = 0.46), and the cumulative incidence of diabetes during a median follow-up of 30
      months (13 vs. 17%; P = 0.66). CONCLUSIONS: Among young Hispanic women at high
      risk for type 2 diabetes, the Pro12Ala variant of the PPAR-gamma receptor gene
      did not explain the failure of approximately 1/3 of subjects to increase their
      insulin sensitivity when placed on troglitazone at a dose of 400 mg/day.

PMID- 15161790
TI  - Acute alcohol consumption improves insulin action without affecting insulin
      secretion in type 2 diabetic subjects.
AB  - OBJECTIVE: Long-term exposure to alcohol is associated with an improvement in
      insulin sensitivity. At this time, however, there is no definitive proof that
      alcohol per se has an effect on the insulin sensitivity index (S(i)) in type 2
      diabetes patients. The aim of the present study was to assess the role of acute
      moderate alcohol intake on insulin sensitivity and insulin secretion in
      comparable subjects with and without type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Frequently sampled intravenous glucose tolerance tests (FSIGTs) were
      performed twice on eight healthy and eight type 2 diabetic volunteers. Forty
      grams of alcohol (vodka 40% wt/vol) or tap water were sipped from time -60 min to
      the end of the FSIGT. RESULTS: Lactate area under the curve (AUC) was higher in
      both groups during the alcohol study than in the control study. Free fatty acid
      (FFA) AUC was higher in type 2 diabetic subjects than in control subjects;
      alcohol slightly reduced FFA by 17% in control subjects (34 +/- 4 mmol. min(-1).
      l(-1); P = 0.1) but significantly decreased FFA by 23% in type 2 diabetic
      subjects (54 +/- 10; P = 0.007). Beta-cell response was markedly reduced in type
      2 diabetic subjects regardless of the type of study. Alcohol significantly
      increased S(i) in both groups. CONCLUSIONS: Acute alcohol consumption improves
      insulin action without affecting beta-cell secretion. This effect may be partly
      due to the inhibitory effect of alcohol on lipolysis. Alcohol intake increases
      insulin sensitivity and may partly explain both the J-shaped relationship between
      the prevalence of diabetes and the amount of alcohol consumption and the
      decreased mortality for myocardial infarction.

PMID- 15161791
TI  - Adipocytokines attenuate the association between visceral adiposity and diabetes
      in older adults.
AB  - OBJECTIVE: To examine whether adiponectin is independently associated with
      diabetes and whether adiponectin and other adipocytokines account for the
      relationship between fat and diabetes. RESEARCH DESIGN AND METHODS: A nested case
      control study from the Health, Aging, and Body Composition (Health ABC) study. We
      measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis
      factor-alpha, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area
      was determined by computed tomography scan. The 519 case subjects had diabetes
      defined by fasting plasma glucose level > or =126 mg/dl or by use of diabetes
      medications. The 519 control subjects had normal glucose tolerance and were
      matched by sex, race, and study site. Sex-specific logistic models were adjusted
      for age, race, site, total adiposity, smoking, and physical activity. RESULTS:
      Higher adiponectin levels were associated with lower risk of diabetes (P <
      0.001). Visceral fat was the only adiposity measure associated with diabetes
      after adjusting for BMI (odds ratio 3.0 [2.1-4.3] in women and 1.3 [1.0-1.6] in
      men, P < 0.001 between-sex comparison). Adipocytokines attenuated the association
      between visceral fat and diabetes for both sexes but more strongly in men (women
      2.3 [1.5-3.3], men 1.1 [0.9-1.4]). In men, adiponectin, IL-6, and PAI-1 remained
      independently associated with diabetes after adjusting for fat depots; in women,
      adiponectin was the only independently associated adipocytokine. Controlling for
      insulin, HDL, triglycerides, and blood pressure did not change these results.
      CONCLUSIONS: Adiponectin is associated with lower odds of diabetes in older men
      and women. Whereas several adipocytokines explained the relationship between
      visceral adiposity and diabetes in men, only adiponectin partially mediated this
      association among women.

PMID- 15161792
TI  - Results of blood inflammatory markers are associated more strongly with toe
      brachial index than with ankle-brachial index in patients with type 2 diabetes.
AB  - OBJECTIVE: Three blood markers of inflammation (high-sensitivity C-reactive
      protein [hsCRP], interleukin [IL]-6, and fibrinogen) were compared with markers
      of atherosclerotic cardiovascular disease (CVD) (history of stroke or cardiac
      ischemia and measured toe-brachial index [TBI]) to determine whether inflammatory
      markers are associated with atherosclerosis in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Of 103 patients with type 2 diabetes, 26 had CVD.
      TBI was plethysmographically determined in both great toes. Serum hsCRP was
      immunonephelometrically determined. Plasma IL-6 was measured by an enzyme
      immunoassay. RESULTS: Both ABI and TBI were lower in diabetic patients with CVD
      than in those without CVD (1.05 +/- 0.19 vs. 1.14 +/- 0.09, P < 0.05, and 0.75 +/
      0.20 vs. 0.95 +/- 0.21, P < 0.001, respectively). By linear regression, right
      TBI but not right ABI showed a significant negative correlation with serum hsCRP
      (r = -0.372, P < 0.01) and plasma fibrinogen (r = -0.224, P < 0.05). Serum hsCRP
      was also negatively correlated with lower TBI, but not lower ABI. We found no
      significant correlation between plasma IL-6 and ABI or TBI. CONCLUSIONS: TBI was
      strongly associated with CVD, serum hsCRP, and plasma fibrinogen. Of these
      inflammatory markers, serum hsCRP may be the most promising marker for vascular
      inflammation.

PMID- 15161793
TI  - Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in
      type 1 diabetes.
AB  - OBJECTIVE: Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic
      patients, denoting autoimmune gastritis and pernicious anemia, which may
      predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric
      carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole
      acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening
      for ECL cell hyper/dysplasia. RESEARCH DESIGN AND METHODS: Sera from 93 type 1
      diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13
      years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE,
      and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance
      liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in
      gastric biopsies. RESULTS: PCA(+) patients had higher gastrin (P < 0.0001) and
      CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio
      [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(
      ) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who
      showed higher CgA levels (P < 0.0001) than subjects without ECL cell
      hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated
      with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5
      HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level
      (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell
      hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested.
      Multivariate linear regression demonstrated that CgA level was determined by ECL
      cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One
      PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric
      carcinoid tumor. CONCLUSIONS: PCA(+) patients, particularly those with high
      gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The
      determination of CgA, but not NSE and 5-HIAA, may complement histology in
      evaluating ECL cell mass.

PMID- 15161794
TI  - The Arg972 variant in insulin receptor substrate-1 is associated with an
      increased risk of secondary failure to sulfonylurea in patients with type 2
      diabetes.
AB  - OBJECTIVE: The aim of this study was to investigate whether diabetic patients
      carrying the Arg(972) insulin receptor substrate-1 (IRS-1) variant are at
      increased risk for secondary failure to sulfonylurea. RESEARCH DESIGN AND
      METHODS: A total of 477 unrelated Caucasian type 2 diabetic patients were
      recruited according to the following criteria: onset of diabetes after age 35
      years, absence of ketonuria at diagnosis, and anti-GAD(-) antibody. Type 2
      diabetes was diagnosed according to the American Diabetes Association criteria.
      Patients with secondary sulfonylurea failure were defined as those requiring
      insulin due to uncontrolled hyperglycemia (fasting plasma glucose >300 mg/dl)
      despite sulfonylurea-metformin combined therapy, appropriate diet, and absence of
      any conditions causing hyperglycemia. RESULTS: Of the total patients, 53 (11.1%)
      were heterozygous for the Arg(972) IRS-1 variant, 1 (0.2%) was homozygous, and
      the remainder (88.7%) were homozygous for the wild-type allele. The genotype
      frequency of the Arg(972) IRS-1 variant was 8.7% among diabetic patients well
      controlled with oral therapy and 16.7% among patients with secondary failure to
      sulfonylurea (odds ratio 2.1 [95% CI 1.18-3.70], P = 0.01). Adjustment for age,
      sex, BMI, metabolic control, age at diagnosis, duration of diabetes, and Pro12Ala
      polymorphism of peroxisome proliferator-activated receptor-gamma2 gene in a
      logistic regression analysis with secondary failure to sulfonylurea as a
      dependent variable did not change this association (2.0 [1.38-3.86], P = 0.038).
      CONCLUSIONS: These data demonstrate that the Arg(972) IRS-1 variant is associated
      with increased risk for secondary failure to sulfonylurea, thus representing a
      potential example of pharmacogenetics in type 2 diabetes.

PMID- 15161795
TI  - Clinical characteristics of children diagnosed with type 1 diabetes through
      intensive screening and follow-up.
AB  - OBJECTIVE: The objective of this study was to determine whether earlier diagnosis
      of diabetes in prospectively followed autoantibody-positive children lowered
      onset morbidity and improved the clinical course after diagnosis. RESEARCH DESIGN
      AND METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) follows
      genetically at-risk children for the development of diabetes. Increased genetic
      risk is identified by family history of type 1 diabetes or expression of diabetes
      associated HLA genotypes. Of the 2,140 prospectively followed children, 112 have
      developed islet autoantibodies and 30 have progressed to diabetes. Diabetes onset
      characteristics and early clinical course of these 30 children followed to
      diabetes were compared with those of 101 age- and sex-matched children
      concurrently diagnosed with diabetes in the community. RESULTS: Pre-diabetic
      children followed to diabetes were less often hospitalized than the community
      cases (3.3 vs. 44%; P < 0.0001). They had a lower mean HbA(1c) at onset (7.2 vs.
      10.9%; P < 0.0001) and 1 month after diagnosis (6.9 vs. 8.6%; P < 0.0001) but not
      after 6 months of diabetes. The mean insulin dose was lower in the DAISY group at
      1 (0.30 vs. 0.51 U. kg(-1). day(-1); P = 0.003), 6 (0.37 vs. 0.58; P = 0.001),
      and 12 months (0.57 vs. 0.72; P = 0.03). There was no difference in growth
      parameters between the two groups. Comparisons limited to children with a family
      history of type 1 diabetes in both groups showed a similar pattern. CONCLUSIONS:
      Childhood type 1 diabetes diagnosed through a screening and follow-up program has
      a less severe onset and a milder clinical course in the first year after
      diagnosis.

PMID- 15161796
TI  - Estimation of resting energy expenditure considering effects of race and diabetes
      status.
AB  - OBJECTIVE: To evaluate the impact of diabetes status and race, in addition to
      other covariables, on the estimation of resting energy expenditure (REE).
      RESEARCH DESIGN AND METHODS: Demographic, anthropometric, and clinical parameters
      were assessed in 166 adults of varying weights. Subjects were categorized by race
      (white versus black) and into three subgroups based on glucose tolerance
      (normoglycemia, impaired glucose tolerance, and type 2 diabetes), termed the
      diabetes status index (DSI). REE was measured by indirect calorimetry. A multiple
      regression model was established for optimal prediction of REE based on
      covariables. RESULTS: An average decrease in REE of 135 kcal/day independent of
      all other variables was observed in blacks (P < 0.001). DSI was found to be a
      significant covariable (P = 0.002) in predicting REE, which was observed to be
      higher in diabetic women. Therefore, race and DSI entered the multiple regression
      equation to predict REE as significant independent variables, together with lean
      body mass (LBM) and age x BMI interaction (P < 0.001). Overall, REE prediction
      resulted in an R(2) of 0.79 and a root mean square error of 136 kcal/day. These
      values indicate that the resultant equations could offer advantages over other
      key published prediction equations. The equations are: 1) REE(female) = 803.8 +
      0.3505 x age x (BMI - 34.524) - 135.0 x race + 15.866 x LBM + 50.90 x DSI; and 2)
      REE(male) = 909.4 + 0.3505 x age x (BMI -34.524) -135.0 x race + 15.866 x LBM 
      9.10 x DSI. The predictive value of the equations did not diminish substantially
      when fat-free mass estimated by skinfold calipers was substituted for dual-energy
      X-ray absorptiometry scan measurements of LBM. CONCLUSIONS: Race and diabetes
      status are important when predicting REE, coupled with LBM, age, BMI, and sex.
      Race and DSI have not been considered in equations commonly used to predict REE.
      Their inclusion could improve individualization of dietary prescriptions for type
      2 diabetic subjects and heterogeneous populations.

PMID- 15161797
TI  - Relation between acanthosis nigricans and insulin sensitivity in overweight
      Hispanic children at risk for type 2 diabetes.
AB  - OBJECTIVE: To investigate in a population of Hispanic children if 1) the presence
      of acanthosis nigricans (AN) is related to insulin sensitivity (S(i)) independent
      of adiposity and 2) scale scoring AN severity adds to the clinical estimation of
      insulin sensitivity, above and beyond the presence or absence AN alone. RESEARCH
      DESIGN AND METHODS: The study population, 131 Hispanic overweight children (mean
      BMI percentile 97.0 +/- 3.1, 72 boys, 59 girls, ages 8-13 years, mean Tanner
      stage 2.4 +/- 1.5) with a family history of type 2 diabetes, underwent a physical
      examination of the neck to determine AN absence or presence (0-1), AN extent
      score (0-4 scale), AN texture score (0-3 scale), and an AN combined score (extent
      + texture; 0-7 scale). S(i) was measured by the frequently sampled intravenous
      glucose tolerance test and minimal modeling. Multivariate linear regression
      analysis was used to determine the role of BMI and AN in predicting S(i).
      RESULTS: BMI was the main predictor of S(i), explaining approximately 41% of the
      variance. The presence of AN explained an additional 4% of the variability in
      S(i); scale scoring of AN extent or texture did not significantly improve the
      prediction. CONCLUSIONS: Although AN is an independent risk factor for insulin
      resistance in overweight Hispanic children at risk for type 2 diabetes, body
      adiposity is the primary determinant of insulin sensitivity. In addition, scale
      scoring AN seems of minimal usefulness in clinically estimating the severity of
      insulin resistance over and above assessing the presence or absence of AN and
      calculating BMI.

PMID- 15161799
TI  - Serum gamma-glutamyltransferase and risk of metabolic syndrome and type 2
      diabetes in middle-aged Japanese men.
AB  - OBJECTIVE: To investigate the association between serum gamma-glutamyltransferase
      (GGT) and risk of metabolic syndrome and type 2 diabetes in Japanese male office
      workers. RESEARCH DESIGN AND METHODS: This study included 2,957 metabolic
      syndrome-free men and 3,260 nondiabetic men aged 35-59 years who did not have
      medication for hepatitis, alanine aminotransferase (ALT) levels higher than three
      times the upper limit of the reference range, or a history of cardiovascular
      disease at study entry. Subjects were reexamined at periodic annual health
      examinations over a 7-year period. We used a modified National Cholesterol
      Education Program definition of metabolic syndrome with BMI instead of waist
      circumference and the revised criteria of the American Diabetes Association for
      type 2 diabetes. RESULTS: With adjustment for age, family history of diabetes,
      BMI, alcohol intake, cigarette smoking, regular physical activity (fasting plasma
      glucose for the risk of type 2 diabetes), and white blood cell (WBC) count, the
      risk of metabolic syndrome and type 2 diabetes increased in correlation with the
      levels of serum GGT, ALT, aspartate aminotransferase (AST), and alkaline
      phosphatase. Additional adjustment for all of the other liver enzymes attenuated
      these associations, but serum GGT remained a significant risk factor for the risk
      of both metabolic syndrome and type 2 diabetes (P for trend <0.001 for both). Top
      one-fifth versus bottom one-fifth relative risks of metabolic syndrome and type 2
      diabetes were 2.23 (95% CI 1.51-3.30) and 2.44 (1.34-4.46), respectively.
      CONCLUSIONS: These results indicate that serum GGT may be an important predictor
      for developing metabolic syndrome and type 2 diabetes in middle-aged Japanese
      men.

PMID- 15161798
TI  - Using metabolic syndrome traits for efficient detection of impaired glucose
      tolerance.
AB  - OBJECTIVE: Efficient detection of impaired glucose tolerance (IGT) is needed to
      implement type 2 diabetes prevention interventions. RESEARCH DESIGN AND METHODS:
      We assessed the capacity of the metabolic syndrome (MetS) to identify IGT in a
      cross-sectional analysis of 3,326 Caucasian Framingham Offspring Study (FOS),
      1,168 Caucasian and 1,812 Mexican-American San Antonio Heart Study (SAHS), 1,983
      Mexico City Diabetes Study (MCDS), and 452 Caucasian, 407 Mexican-American, and
      290 African-American Insulin Resistance Atherosclerosis Study (IRAS) men and
      women aged 30-79 years who had a clinical examination and an oral glucose
      tolerance test (OGTT) during 1987-1996. Those with diabetes treatment or fasting
      plasma glucose > or =7.0 mmol/l were excluded (MetS was defined by Third Report
      of the National Cholesterol Education Program's Adult Treatment Panel criteria
      and IGT as 2-h postchallenge glucose [2hPG] > or =7.8 mmol/l). We calculated
      positive (PPV) and negative predictive values (NPV), population attributable risk
      percentages (PAR%), age- and sex-adjusted odds ratios (ORs), and areas under the
      receiver operating characteristic curve (AROCs) associated with MetS traits.
      RESULTS: Among FOS, SAHS, and MCDS subjects, 24-43% had MetS and 15-23% had IGT
      (including 2-5% with 2hPG > or =11.1 mmol/l). Among those with MetS, OR for IGT
      were 3-4, PPV were 0.24-0.41, NPV were 0.84-0.91, and PAR% were 30-40%. Among
      subjects with MetS defined by impaired fasting glucose (IFG) and any two other
      traits, OR for IGT were 9-24, PPV were 0.62-0.89, NPV were 0.78-0.87, and PAR%
      were 3-12%. Among IRAS subjects, 24-34% had MetS and 37-41% had IGT. Among those
      with MetS, ORs for IGT were 3-6, PPVs were 0.57-0.73, and NPVs were 0.67-0.72. In
      logistic regression models, IFG, large waist, and high triglycerides were
      independently associated with IGT (AROC 0.71-0.83) in all study populations.
      CONCLUSIONS: The MetS, especially defined by IFG, large waist, and high
      triglycerides, efficiently identifies subjects likely to have IGT on OGTT and
      thus be eligible for diabetes prevention interventions.

PMID- 15161800
TI  - Insulin resistance, impaired early insulin response, and insulin propeptides as
      predictors of the development of type 2 diabetes: a population-based, 7-year
      follow-up study in 70-year-old men.
AB  - OBJECTIVE: Defects in insulin secretion and insulin action are the major
      abnormalities in the development of type 2 diabetes. In middle-aged subjects,
      elevated plasma proinsulin has been found to predict type 2 diabetes. Therefore,
      our aim was to study the longitudinal relationships between baseline
      determinations of insulin sensitivity index (S(i)) assessed by euglycemic insulin
      clamp, the early insulin response (EIR) at an oral glucose tolerance test (OGTT),
      fasting intact proinsulin, 32-33 split proinsulin and specific insulin, and the
      development of type 2 diabetes in a population-based cohort of 70-year-old
      nondiabetic men (n = 667) with 7-year follow-up. RESEARCH DESIGN AND METHODS: A
      euglycemic insulin clamp study and a 75-g OGTT were performed at baseline, and
      fasting peptide concentrations were measured using specific two-site immunometric
      assays. Results from logistic regression models are presented as odds ratios
      (ORs) with 95% CIs for a 1-SD increase in the predictor variable. RESULTS: In
      separate multivariate analyses adjusted for EIR (OR 0.72, 95% CI 0.59-0.89) and
      S(i) (0.68, 0.58-0.88), 32-33 split proinsulin (1.49, 1.18-1.88) or intact
      proinsulin (1.30, 1.04-1.63) were significantly associated with the development
      of type 2 diabetes, whereas specific insulin (1.24, 0.91-1.66) was not. The
      significant associations between 32-33 split or intact proinsulin and the
      development of type 2 diabetes were unaltered after adjustment for BMI and
      glucose tolerance. CONCLUSIONS: Insulin propeptides predicted type 2 diabetes
      over a 7-year period in elderly men, independent of the EIR and S(i).

PMID- 15161801
TI  - Impaired insulin sensitivity, insulin secretion, and glucose effectiveness
      predict future development of impaired glucose tolerance and type 2 diabetes in
      pre-diabetic African Americans: implications for primary diabetes prevention.
AB  - OBJECTIVE: We examined the determinants of impaired glucose tolerance (IGT) and
      type 2 diabetes in first-degree relatives of African-American type 2 diabetic
      patients over 5-8 years (median 6). RESEARCH DESIGN AND METHODS: A total of 81
      healthy subjects (age 41.5 +/- 4.8 years; BMI 31.3 +/- 3.6 kg/m(2)) participated
      in the study. Each subject underwent an oral glucose tolerance test (OGTT) and a
      frequently sampled intravenous glucose tolerance test at baseline. Insulin
      sensitivity index (S(i)) and glucose effectiveness index (S(g)) were determined
      by the minimal model method. Homeostasis model assessment (HOMA) was used to
      estimate insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B). A total
      of 18 subjects progressed to either IGT or type 2 diabetes (progressors), whereas
      19 subjects maintained normal glucose tolerance (nonprogressors). RESULTS:
      Comparing the progressors and nonprogressors, mean fasting serum glucose levels
      (95 +/- 8 vs. 80 +/- 14 mg/dl, P < 0.01) and 2-h serum glucose levels (149 +/- 27
      vs. 100 +/- 60 mg/dl, P < 0.01) as well as 2-h serum insulin levels (117 +/- 81
      vs. 72 +/- 87 microU/ml, P < 0.01) during OGTT were higher at baseline. Mean
      acute first-phase insulin secretion (205 +/- 217 vs. 305 +/- 230 microU/ml), HOMA
      %B (148 +/- 60 vs. 346 +/- 372, P < 01), S(i) (1.61 +/- 1.13 vs. 2.48 +/- 1.25 x
      10(-4). min(-1) [microU/ml](-1)), and S(g) (1.48 +/- 0.61 vs. 2.30 +/- 0.97 x 10(
      2). min(-1)) were lower in the progressors than in the nonprogressors at
      baseline. Mean HOMA-IR (3.31 +/- 1.64 vs. 2.36 +/- 1.64) was significantly
      greater in the progressors than the nonprogressors. At the time of diagnosis of
      glucose intolerance (IGT + diabetes), HOMA-%B (101 +/- 48 vs. 148 +/- 60, P <
      0.001) and HOMA-IR (5.44 +/- 2.55 vs. 3.31 +/- 1.64, P < 0.003) deteriorated in
      the progressors versus baseline. CONCLUSIONS: We conclude that nondiabetic, first
      degree relatives of African-American type 2 diabetic patients who progressed to
      IGT and type 2 diabetes manifest triple defects (decreased insulin secretion,
      insulin action, and glucose effectiveness) that antecede the disease.

PMID- 15161802
TI  - Acute hypoglycemia impairs nonverbal intelligence: importance of avoiding ceiling
      effects in cognitive function testing.

PMID- 15161803
TI  - Negative pressure suction during blood sampling may reduce the difference in self
      monitoring of blood glucose results between fingertip pricking and forearm
      pricking.

PMID- 15161804
TI  - Low adiponectin levels predict type 2 diabetes in Mexican children.

PMID- 15161805
TI  - Polyunsaturated fatty acid consumption may play a role in the onset and
      regression of microalbuminuria in well-controlled type 1 and type 2 diabetic
      people: a 7-year, prospective, population-based, observational multicenter study.

PMID- 15161806
TI  - Diabetic somatic neuropathies.

PMID- 15161807
TI  - Use and abuse of HOMA modeling.
AB  - Homeostatic model assessment (HOMA) is a method for assessing beta-cell function
      and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide
      concentrations. It has been reported in >500 publications, 20 times more
      frequently for the estimation of IR than beta-cell function. This article
      summarizes the physiological basis of HOMA, a structural model of steady-state
      insulin and glucose domains, constructed from physiological dose responses of
      glucose uptake and insulin production. Hepatic and peripheral glucose efflux and
      uptake were modeled to be dependent on plasma glucose and insulin concentrations.
      Decreases in beta-cell function were modeled by changing the beta-cell response
      to plasma glucose concentrations. The original HOMA model was described in 1985
      with a formula for approximate estimation. The computer model is available but
      has not been as widely used as the approximation formulae. HOMA has been
      validated against a variety of physiological methods. We review the use and
      reporting of HOMA in the literature and give guidance on its appropriate use
      (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring
      beta-cell function in isolation). The HOMA model compares favorably with other
      models and has the advantage of requiring only a single plasma sample assayed for
      insulin and glucose. In conclusion, the HOMA model has become a widely used
      clinical and epidemiological tool and, when used appropriately, it can yield
      valuable data. However, as with all models, the primary input data need to be
      robust, and the data need to be interpreted carefully.

PMID- 15161808
TI  - Lipids and lipoproteins in patients with type 2 diabetes.
AB  - Insulin resistance and type 2 diabetes are associated with a clustering of
      interrelated plasma lipid and lipoprotein abnormalities, which include reduced
      HDL cholesterol, a predominance of small dense LDL particles, and elevated
      triglyceride levels. Each of these dyslipidemic features is associated with an
      increased risk of cardiovascular disease. Increased hepatic secretion of large
      triglyceride-rich VLDL and impaired clearance of VLDL appears to be of central
      importance in the pathophysiology of this dyslipidemia. Small dense LDL particles
      arise from the intravascular processing of specific larger VLDL precursors.
      Typically, reduced plasma HDL levels in type 2 diabetes are manifest as
      reductions in the HDL(2b) subspecies and relative or absolute increases in
      smaller denser HDL(3b) and HDL(3c). Although behavioral interventions such as
      diet and exercise can improve diabetic dyslipidemia, for most patients,
      pharmacological therapy is needed to reach treatment goals. There are several
      classes of medications that can be used to treat lipid and lipoprotein
      abnormalities associated with insulin resistance and type 2 diabetes, including
      statins, fibrates, niacin, and thiazolidinediones. Clinical trials have shown
      significant improvement in coronary artery disease after diabetic dyslipidemia
      treatment.

PMID- 15161809
TI  - Insulin for toddlers with difficult diabetes.

PMID- 15161810
TI  - Diabetes complications.

PMID- 15161811
TI  - Understanding the associations between statewide diabetes prevalence and air
      pollution emissions.

PMID- 15161812
TI  - High prevalence of immunounreactive albumin in urine from diabetic patients with
      a low glomerular filtration rate and normoalbuminuria.

PMID- 15161813
TI  - The metabolic syndrome in Inuit.

PMID- 15161814
TI  - Intrinsic motivation and glycemic control in adolescents with type 1 diabetes.

PMID- 15161815
TI  - The association of NAD(P)H oxidase p22phox with diabetic nephropathy is still
      uncertain: response to Hodgkinson, Millward, and Demaine.

PMID- 15161816
TI  - Adiponectin in youth: response to Bacha et al.

PMID- 15161820
TI  - Kidney function during and after withdrawal of long-term irbesartan treatment in
      patients with type 2 diabetes and microalbuminuria: response to Andersen,
      Brochner-Mortensen, and Parving.

PMID- 15161822
TI  - Effects of optically imposed astigmatism on emmetropization in infant monkeys.
AB  - PURPOSE: Although astigmatism is prevalent during early infancy, the influence of
      astigmatism on early refractive development is unclear. This study was undertaken
      to determine the effects of astigmatism on emmetropization in monkeys. METHODS:
      Infant rhesus monkeys (n = 39) were exposed to optically simulated astigmatism in
      one or both eyes from approximately 1 to 4 months of age. With-the-rule, against
      the-rule, and oblique astigmatisms were optically simulated by appropriately
      orienting the principal meridians of the spherocylindrical treatment lenses
      (+1.50 -3.00 D x 90 degrees, 180 degrees, 45 degrees, or 135 degrees; i.e., +1.50
      and -1.50 D powers in the two principal meridians). Refractive development was
      assessed every 2 to 3 weeks by cycloplegic retinoscopy, keratometry and corneal
      videotopography, and A-scan ultrasonography. Data from 19 control monkeys,
      including 3 animals that were reared with binocular plano lenses, were used for
      comparison purposes. RESULTS: Most of the cylinder-lens-reared monkeys,
      regardless of the orientation of the imposed astigmatism, showed clear signs of
      either hyperopic or myopic growth compared with control monkeys. The
      distributions of refractive error and vitreous chamber depth both showed bimodal
      patterns that differed from normal by amounts equivalent to the optical powers of
      the principal meridians of the treatment lenses. More frequently, refractive
      development was biased toward the eye's least-hyperopic focal plane. The
      refractive changes were mainly axial. After lens removal, the lens-reared monkeys
      recovered and as a group exhibited refractive errors and axial dimensions similar
      to those in control monkeys. CONCLUSIONS: In the presence of significant amounts
      of astigmatism, emmetropization is directed toward one of the two focal planes
      associated with the astigmatic principal meridians and not the circle of least
      confusion. These results suggest that the mechanisms responsible for
      emmetropization are insensitive to stimulus orientation and the global form of
      the retinal image. It appears that emmetropization seeks out the image plane that
      contains the maximum effective contrast integrated across spatial frequency and
      stimulus orientation.

PMID- 15161821
TI  - Animal models of dry eye: a critical assessment of opportunities and limitations.

PMID- 15161823
TI  - Cytoarchitecture of choroidal capillary endothelial cells.
AB  - PURPOSE: To describe the cytoarchitecture of the choroidal capillary endothelial
      cells, especially as it relates to cellular processes that protrude through the
      basal lamina into Bruch's membrane (BM). METHODS: Human donor eyes and monkey and
      hamster eyes were examined by transmission electron microscopy and freeze
      fracture replication. The number of endothelial cell processes and the
      characteristics of the processes and surrounding structures were determined in
      the maculae of human eyes and correlated with age-related changes in neighboring
      structures. RESULTS: Endothelial cell processes were observed in eyes of all
      species examined and at all ages. They typically occurred at sites of focally
      thickened, nonfenestrated regions of the endothelial cells. The basal lamina
      adjacent to the processes was often hypertrophic and associated deposits of long
      spacing collagen (LSC) were observed frequently. In humans, there was no
      correlation between the number of processes per 100 micro m of the BM with age,
      sex, cause of death, postmortem time, RPE autofluorescence, or RPE residual body
      content. There was a weak linear association with the thickness of the BM.
      CONCLUSIONS: The finding of cellular processes of choroidal capillary endothelial
      cells penetrating their basal laminae is normal. These processes may serve to
      stabilize choroidal endothelial cells physically and play an important structural
      role in the maintenance of patency of the choriocapillaris. It is also possible
      that they have additional functions, as suggested for similar processes in other
      tissues. They are not necessarily the harbinger of choroidal neovascularization,
      although growth of new vessels may result from distortion of this normal
      attribute.

PMID- 15161824
TI  - Developmental expression profile of the optic atrophy gene product: OPA1 is not
      localized exclusively in the mammalian retinal ganglion cell layer.
AB  - PURPOSE: Autosomal dominant optic atrophy (ADOA) is characterized by primary
      degeneration of retinal ganglion cells and atrophy of the optic nerve. The OPA1
      gene encodes a 960-amino-acid protein. In the current study the temporal and
      spatial localization of OPA1 were examined in developing and adult murine ocular
      tissues and the adult human eye. Because the Bst/+ mouse has been postulated as a
      model of ADOA, the mOPA1 expression in the Bst/+ retina was also examined.
      METHODS: A polyclonal antibody generated against a C-terminal peptide of OPA1 was
      used to assess by immunohistochemistry the expression of mOPA1 in the wild-type
      embryonic and postnatal mouse ocular tissues and the Bst/+ retina. Western blot
      analyses of total proteins from a panel of adult human tissues were used to
      examine the expression of human OPA1, and spatial localization was assessed by
      immunohistochemistry. RESULTS: The ocular expression of mOPA1 begins at E15 in
      the inner retina in a location corresponding to that of the subsequently
      developing ganglion cell layer (GCL) and peaks between postnatal day (P)0 and P1
      in the retina and the optic nerve. There is a sharp decline in mOPA1 expression
      after P2, but it is expressed at a basal level until at least P12 in the GCL,
      inner plexiform layer (IPL), and inner nuclear layer (INL) of the retina as well
      as in the optic nerve. In the adult Bst/+ retina, mOPA1 is strongly expressed in
      the GCL and IPL and weakly in the INL. In the adult human eye, OPA1 is expressed
      in the GCL, IPL, INL, and outer plexiform layer (OPL) of the retina and in the
      optic nerve, where it is observed only in the myelinated region. CONCLUSIONS:
      OPA1 is not restricted to the GCL of the mammalian retina, and its expression
      extends into the IPL, INL, and OPL. OPA1 is distinctly expressed in the
      myelinated region beyond the lamina cribrosa in the human optic nerve, whereas
      its expression is weaker in the mouse optic nerve. In the Bst/+ mouse retina,
      despite the structural defects, mOPA1 expression is comparable to that observed
      in the wild-type adult mouse retina. These observations suggest a wider role for
      OPA1 than previously anticipated.

PMID- 15161825
TI  - Expression, localization, and correlation of N-myristoyltransferase and its
      inhibitor in bovine eye.
AB  - PURPOSE: N-myristoyltransferase (NMT) is a ubiquitously distributed eukaryotic
      enzyme that catalyzes myristoylation of proteins. Very little is known about the
      process of myristoylation, particularly in the eye. In the present study, the
      distribution, expression, and correlation of NMT and its inhibitor (NMT inhibitor
      protein, NIP) in the bovine eye were investigated. METHODS: Whole bovine eyes
      were either homogenized or regionally dissected to determine the activity and
      localization of NMT and NIP. Dissected tissues were homogenized, and Western blot
      analysis was performed using polyclonal anti-NMT and anti-NIP antibodies. The NMT
      activity was assayed using cAMP-dependent protein kinase or pp60(src) derived
      peptide as a substrate. Fresh samples were then prepared for immunohistochemical
      analysis and probed with polyclonal anti-NMT and anti-NIP antibodies. RESULTS:
      The total bovine eye cytosolic fraction displayed both NMT and NIP expression.
      NMT was present in all the regions of the eye at various levels of expression.
      The highest expression of NMT was in the cornea, whereas NIP was present in the
      retina, optic nerve, sclera, and choroid only. NIP expression was the highest in
      the optic nerve, sclera, and retina. NMT activity was observed in the cornea,
      iris, and retina after DEAE-Sepharose CL-6B column chromatography. The inhibitory
      activity of crude homogenate on recombinant human NMT activity was found to be
      greater for optic nerve and choroid. Immunohistochemistry results displayed
      similar findings. CONCLUSIONS: The varied expression of NMT in different regions
      of the eye reveals a regulatory relationship of NMT with NIP. These findings
      indicate that NMT and NIP are present in various regions of the eye and will lead
      to further understanding of visual signaling in ocular cells.

PMID- 15161826
TI  - Efficient gene transfer into retinal cells using adenoviral vectors: dependence
      on receptor expression.
AB  - PURPOSE: A number of ocular diseases are potentially amenable to gene therapy
      interventions if appropriate vectors for the targeted administration of
      therapeutic genes can be identified. In vitro and in vivo transduction efficiency
      of a Group C serotype 5 adenoviral vector containing the fiber domain derived
      from a Group B serotype 35 adenovirus and the gene encoding green fluorescent
      protein (AdV5/F35-GFP) was compared to an AdV5-GFP vector for transgene delivery
      to human retinoblastoma and to human and murine retinas. METHODS: The
      distribution of the adenoviral receptors CAR and CD46 on normal and malignant
      retinal tissues was determined using immunohistochemistry. Human retinoblastoma
      cells were incubated with either AdV5-GFP or AdV5/F35-GFP, and the expression of
      the reporter protein was compared using quantitative fluorescence and fluorescent
      activated cell sorting. Mice were given a single subretinal injection of either
      viral vector, and eyes were enucleated at specified times after injection for
      histopathologic examination. Human cadaver eyes were similarly examined ex vivo.
      RESULTS: CAR was expressed in retina except in photoreceptor outer segments. CD46
      was expressed in photoreceptor inner and outer segments. Both vectors efficiently
      transduced the human retinoblastoma cells in vitro. However, the amount of the
      transgene expressed using AdV5/F35-GFP was more than sixfold greater than that
      when AdV5-GFP was used. In vivo, AdV5/F35-GFP at doses as low as 10(5) infectious
      units (IU) transduced cells in all layers of the retina especially photoreceptors
      and occasional neuronal cells, and Muller cells as well as retinal pigment
      epithelial cells, whereas AdV5-GFP transduced only retinal pigment epithelial
      cells and occasional photoreceptors and Muller cells. CONCLUSIONS: AdV5/F35
      chimeric vectors may be superior to AdV5 for gene therapy applications targeting
      the photoreceptor.

PMID- 15161827
TI  - Increased 8-hydroxy-2'-deoxyguanosine in leukocyte DNA in Leber's hereditary
      optic neuropathy.
AB  - PURPOSE: This study was conducted to test the hypothesis that oxidative stress is
      involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON). The
      level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized DNA base common in
      cells undergoing oxidative stress, was measured in leukocyte DNA from patients
      with LHON and normal control subjects. METHODS: The 8-OHdG and deoxyguanosine
      (dG) content in leukocyte DNA from 25 patients with LHON with an 11778
      mitochondrial (mt)DNA mutation, 14 asymptomatic maternal relatives, and 27
      unrelated normal control subjects were measured using high-performance liquid
      chromatography and electrochemical detection methods. RESULTS: The mean 8
      OHdG/10(5) dG ratio from leukocyte DNA was 1.34 +/- 0.99 in patients with LHON,
      1.00 +/- 0.91 in their asymptomatic maternal relatives, and 0.31 +/- 0.20 in
      normal control subjects, respectively. There was a statistically significant
      difference in the mean 8-OHdG/10(5) dG ratio between patients with LHON and
      normal control subjects and between asymptomatic maternal relatives and normal
      control subjects. The difference between patients with LHON and asymptomatic
      maternal relatives did not reach statistical significance. CONCLUSIONS: Patients
      with LHON with an 11778 mtDNA mutation had higher oxidative DNA damage. Oxidative
      stress has a key role in the pathogenesis of LHON.

PMID- 15161829
TI  - Mutation spectrum and founder chromosomes for the ABCA4 gene in South African
      patients with Stargardt disease.
AB  - PURPOSE: To assess the mutation spectrum of ABCA4 underlying Stargardt disease
      (STGD) in South Africa (SA) and to determine whether there is a single or a few
      founder chromosomes in SA STGD families. METHODS: Sixty-four probands exhibiting
      the STGD phenotype were screened for mutations in the 50 exons of ABCA4 by single
      strand conformational polymorphism-heteroduplex analysis sequencing and
      restriction fragment length polymorphism analysis. Microsatellite marker
      haplotyping was used to determine the ancestry in 10 families. RESULTS: Fifty
      seven ABCA4 disease-associated alleles were identified that comprised 16
      different sequence variants, of which two were novel, in 40 individuals of the
      cohort of 64 subjects. The most common variants identified included the C1490Y,
      L2027F, R602W, V256splice, R152X, and 2588G-->C mutations. The C1490Y variant was
      the most common disease-associated variant identified (19/64 subjects) and was
      absent in 392 control chromosomes. At least 10 ABCA4 disease-associated
      haplotypes were identified. Two of these haplotypes, which carried the C1490Y
      mutation, were identified in three unrelated families. CONCLUSIONS: Results
      suggest that ABCA4 is the major gene underlying STGD in the cohort investigated.
      Five of the six common sequence variants identified were at a higher frequency in
      the SA cohort than reported in published data on individuals of similar ancestry.
      The mutation and haplotype data suggests that there are several ancestral
      haplotypes underlying STGD in SA. There seems to be at least two different
      origins for the common C1490Y mutation, as well as two for the R602W mutation,
      thereby suggesting several founder effects for STGD in SA.

PMID- 15161828
TI  - Expression of the alpha4 integrin subunit gene promoter is modulated by the
      transcription factor Pax-6 in corneal epithelial cells.
AB  - PURPOSE: Expression of several membrane-bound integrins is thought to be altered
      during corneal wound healing as a consequence of the massive secretion of
      fibronectin occurring during this process. Examination of the alpha4 integrin
      subunit gene promoter revealed the presence of three putative binding sites for
      the transcription factor Pax-6 expressed in the basal cells of the corneal
      epithelium during corneal wound healing. This study was undertaken to investigate
      whether the alpha4 integrin subunit is expressed in primary cultures of rabbit
      corneal epithelial cells (RCECs) and to test whether Pax-6 binds the alpha4 gene
      promoter and regulates its transcriptional activity. METHODS: Both flow cytometry
      and immunocytochemical analyses, along with an antibody-directed receptor
      interference assay, were used to examine expression of the alpha4 subunit in
      RCECs. Expression of Pax6 was investigated by immunoblot analysis. Binding of
      PAX6 to the alpha4 gene promoter was tested in electrophoretic mobility shift
      assays (EMSAs). The regulatory influence exerted by Pax6 on the alpha4 promoter
      was studied by transfections in RCECs. RESULTS: Expression of alpha4 was detected
      at both the mRNA and protein levels. Pax-6 was expressed in a cell-density
      dependent manner in RCECs and altered the activity of the alpha4 promoter by
      interacting with multiple sites in both the promoter and 5'-flanking sequences.
      Pax-6 was also identified as the major protein component from the Bp5 complex,
      one of five protein complexes reported to bind the alpha4.1 element from the
      alpha4 basal promoter in vitro. CONCLUSIONS: These results provide evidence that
      the integrin subunit alpha4 and Pax-6 are coexpressed in RCECs and raise the
      possibility that Pax-6 directly regulates the expression of the alpha4 gene
      during corneal wound healing.

PMID- 15161830
TI  - Genetic polymorphisms and retinopathy of prematurity.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is a major problem among very preterm
      survivors of neonatal intensive care. Neovascularization of the retina is
      prominent in the proliferative stages of ROP and is under the control of several
      factors such as vascular endothelial growth factor (VEGF). This study was
      undertaken on the hypothesis that genetic polymorphisms of VEGF, transforming
      growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha would occur more
      frequently in preterm infants with progressive ROP than in those with mild or no
      disease. METHODS: The frequencies of VEGF -634 G-->C, VEGF *936 C-->T, TNF-alpha 
      308 G-->A, and TGF-beta -509 C-->T were determined in DNA from 91 infants who had
      received treatment for threshold ROP and 97 comparison infants. RESULTS: The
      frequencies of the VEGF *936 C-->T, TNF-alpha -308 G-->A and TGF-beta -509 C-->T
      polymorphisms were similar in both groups. The distribution of alleles at VEGF 
      634 was significantly different between the two groups (P = 0.03). Homozygotes
      for the G allele, associated with higher VEGF production were twice as likely to
      have threshold ROP. CONCLUSIONS: The progression of ROP to threshold ROP in very
      preterm infants may be influenced by genetic differences in VEGF production.
      Future efforts at prevention of threshold ROP may be directed toward blocking
      excess production of VEGF.

PMID- 15161832
TI  - Improved mobility and independence of night-blind people using night-vision
      goggles.
AB  - PURPOSE: To investigate whether the use of night-vision goggles (NVGs) by night
      blind people improves their mobility and sense of independence under dark
      circumstances. METHODS: Twenty night-blind subjects with retinitis pigmentosa
      were requested to walk predetermined routes at night with and without NVGs. The
      number of unintended contacts with obstacles (hits) and the percentage of
      preferred walking speed (PPWS) en route were assessed in three different
      situations: a darkened indoor corridor; a moderately lit outdoor residential
      area; and a well-lit outdoor shopping area. Assessments were performed before and
      after a 5-week training period, during which the subjects practiced using NVGs in
      their own surroundings, registered their experiences in a journal, and filled out
      questionnaires. RESULTS: The mean number of hits in the darkened corridor
      declined from eight to two when NVGs were used. Mean PPWS (34%) did not improve.
      In the residential area, mean hits declined from eight to practically zero and
      mean PPWS increased from 60% to 72% (after training to 78%). In the shopping
      area, subjects walked at 93% PPWS without any hits and showed no improvement with
      NVGs. Subjective scores revealed a good sense of orientation, feelings of safety
      and tranquility and an increase in independent mobility when NVGs were used.
      CONCLUSIONS: Using NVGs seems to improve nighttime mobility in dark outdoor
      conditions by decreasing unintended contacts with obstacles and increasing
      walking speed. Use of NVGs increased independent activities in these subjects and
      was generally positively evaluated for everyday outdoor use.

PMID- 15161831
TI  - Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head
      measurements using StratusOCT.
AB  - PURPOSE: The measurement reproducibility of the third generation of commercial
      optical coherence tomography, OCT-3 (StratusOCT, software ver. A2, Carl Zeiss
      Meditec Inc., Dublin, CA) was investigated. The nerve fiber layer (NFL)
      thickness, macula thickness map, and optic nerve head (ONH) parameters in normal
      eyes were studied. METHODS: Ten normal subjects were imaged six times (three
      before and three after dilation) per day, and the series was repeated on three
      different days. The order of the scans before pupil dilation was randomized in
      each of the 3 days of scanning. After pupil dilation, the scans were also
      randomized in each of the 3 days of scanning. Each series was performed
      separately for standard-density (128 A-scans per macular and ONH image and 256 A
      scans per NFL image) and high-density (512 A-scans per image for all three scan
      types) scanning. RESULTS: The mean macular thickness was 235 +/- 9.8 micro m. A
      scan density (or image acquisition speed) had a statistically significant effect
      (P < 0.05) on the reproducibility of the mean macular thickness, macular volume,
      and a few sectors of the macular map. No significant dilation effect was found
      for any of the macular parameters. The best intraclass correlation coefficient
      (ICC; 94%) for macular scans was found for dilated high-density scanning, with an
      intervisit SD of 2.4 micro m and an intravisit SD of 2.2 micro m. The mean NFL
      thickness for standard scanning was 98 +/- 9 micro m. NFL reproducibility showed
      mixed results and had interactions between scan density and dilation for some
      parameters. For most of the NFL parameters, reproducibility was better with
      dilated standard-density scanning. The mean NFL thickness ICC for dilated
      standard scanning was 79%, with an intervisit SD of 2.5 micro m and an intravisit
      SD of 1.6 micro m. For the ONH analysis, the reproducibility was better for
      dilated standard-density scanning for almost all the parameters, except for disc
      area, horizontal integrated rim volume, and vertical integrated rim area, which
      were better before dilation. The best reproducibility was found for cup-to-disc
      ratio (ICC = 97%, with intervisit SD of 0.04 micro m and intravisit SD of 0.02
      micro m). CONCLUSIONS: StratusOCT demonstrated reproducible measurements of NFL
      thickness, macular thickness, and optic nerve head parameters. The best
      reproducibility was found for dilated standard scanning for NFL and ONH
      parameters and for dilated high-density scanning for macular parameters.

PMID- 15161833
TI  - Prevalence and associations of epiretinal membranes in latinos: the Los Angeles
      Latino Eye Study.
AB  - PURPOSE: To determine age- and gender-specific prevalence and associations of
      epiretinal membranes (ERMs) in adult Latinos. METHODS: The Los Angeles Latino Eye
      Study (LALES) is a population-based study of eye disease among Latinos aged 40 or
      more years. Complete ophthalmic examinations included stereoscopic fundus
      photography. Masked photographic grading was used to identify and classify ERMs
      as cellophane macular reflex (CMR) without retinal folds or preretinal macular
      fibrosis (PMF) with folds. RESULTS: Of the 6142 persons examined at the clinic,
      5982 (97%) had gradable retinal photographs. The mean age of the participants was
      54.7 +/- 10.7 years; 58% were women. ERMs were present in 18.5% (95% confidence
      interval [CI]: 17.5%-19.5%) of the participants. Of the participants with ERMs,
      19.9% had bilateral ERMs. The prevalence of ERMs increased from 10.1% in persons
      40 to 49 years of age to 35.7% in those aged 70 to 79 years and was 22.5% in
      persons aged 80 years or more. The prevalence was similar in men and women. CMR
      was present in 16.3% (95% CI: 15.3%-17.2%) and PMF in 2.2% (95% CI: 1.9%-2.6%).
      Retinal folds involved the fovea in 11% of PMF cases. On average, eyes with
      central PMF had poorer visual acuity than did eyes without (P < 0.0002).
      Epiretinal membranes (ERMs) were present in 71% of eyes with macular holes. ERMs
      were also more common in individuals who had undergone cataract surgery (39.9%),
      those with proliferative diabetic retinopathy (25.7%), and those with any retinal
      disease (27.5%). CONCLUSIONS: ERMs occur frequently in Latinos, often
      bilaterally. The associations of ERMs with proliferative retinopathy, retinal
      lesions, macular holes, and cataract surgery were confirmed. Central PMF is
      associated with reduced visual acuity.

PMID- 15161834
TI  - Noninvasive assessment of corneal sensitivity in young and elderly diabetic and
      nondiabetic subjects.
AB  - PURPOSE: To investigate the effect of age and diabetes on corneal sensitivity
      using the noncontact corneal aesthesiometer (NCCA). METHODS: One hundred sixteen
      nondiabetic subjects and 111 diabetic subjects (33 type I and 78 type II) were
      recruited and divided into three age groups: Young (<or=29 years), Middle (30-59
      years) and Older (>or=60 years). The exclusion criteria included patients with
      severe retinopathy requiring treatment, a history of invasive ocular surgery, or
      a history of conditions known to affect corneal sensitivity. The corneal cooling
      sensation threshold, for the right eye of each subject, was assessed with a
      double-staircase method-of-limits technique with the NCCA. This instrument uses a
      controlled pulse of air to produce a small, localized reduction in the surface
      temperature of the eye, which is detected by the nerves in the corneal
      epithelium. RESULTS: Analysis of the scatterplot of each subject's central
      cooling sensation threshold revealed a gradual loss of sensitivity with
      increasing age (nondiabetic, r(2) = 0.349; diabetic, r(2) = 0.131). Within the
      nondiabetic group, inter-age-group comparisons found significant differences
      between the central corneal cooling sensation thresholds for the three age groups
      (t-test, P < 0.01). Within the diabetic group, a significant difference was found
      between the Middle and Older categories only (t-test, P < 0.05). In summary, the
      Young group was more sensitive than the Middle group, which was more sensitive
      than the Older group. Within both type I and type II diabetic subjects, there was
      neither a significant relationship between duration of the disease and corneal
      sensitivity (t-test, P > 0.05) nor a gender-based difference (t-test, P > 0.05).
      CONCLUSIONS: There is a gradual reduction in corneal sensitivity with increasing
      age in both nondiabetic subjects and diabetic subjects, along with an increasing
      variation in the measured threshold. There is no relationship between corneal
      sensitivity and the time since diagnosis of diabetes for a thermally cooling
      stimulus, suggesting that the A partial differential and C fibers of the corneal
      innervation are affected differently by abnormal glucose metabolism in the
      diabetic cornea.

PMID- 15161836
TI  - Temporal changes in optical quality of air-tear film interface at anterior cornea
      after blink.
AB  - PURPOSE: To examine temporal changes in the optical quality of the air-tear film
      interface at the anterior cornea after a blink. METHODS: Corneal aberrations were
      determined in fifteen healthy subjects at 1 second time intervals after a blink,
      up to a total elapsed time of 15 seconds. Corneal aberrations were obtained from
      corneal elevation maps measured using a Tomey TMS-2N topographer and custom
      software. All data were decomposed using Zernike polynomials to yield the root
      mean square (RMS) wavefront deviations, in micrometers, for two pupil diameters
      (3 and 7 mm). RESULTS: Total wavefront aberration decreased slightly with time in
      the first few seconds after a blink for both pupil diameters, reaching a minimum
      after approximately 6 seconds. Thereafter aberrations increased steadily,
      exceeding the immediate postblink level after approximately 10 seconds.
      CONCLUSIONS: In normal subjects, the contribution of the anterior cornea to the
      overall ocular aberration remains reasonably stable over the normal interblink
      interval (approximately 4 seconds) but rises to levels which could perceptibly
      degrade retinal image quality under circumstances where the interblink interval
      is increased to exceed 10 seconds, as may occur during the use of visual display
      screens or when performing difficult tasks.

PMID- 15161835
TI  - Proliferative response of corneal endothelial cells from young and older donors.
AB  - PURPOSE: To compare the effect of epidermal growth factor (EGF), nerve growth
      factor (NGF), platelet-derived growth factor-BB (PDGF-BB), bovine pituitary
      extract, and fetal bovine serum (FBS), alone or in combination, on proliferation
      of human corneal endothelial cells (HCEC) cultured from young (<30 years old) and
      older donors (>50 years old). METHODS: Corneas from donors 2 to 79 years old were
      obtained from the National Disease Research Interchange. Descemet's membrane with
      intact endothelium was dissected. Cells were isolated by EDTA treatment and
      cultured to confluence. The HCEC marker, antibody 9.3.E, tested for pure
      endothelial populations. Antibody Ki67 and ZO-1 tested either before or after
      cultured cells reached confluence to indicate cell proliferation and cell-cell
      contact formation. Cell morphology was documented by inverted phase-contrast
      microscopy. Passages I through VII were used to test the effect of various
      factors on cell proliferation. For each study, equal numbers of cells were
      seeded, maintained overnight in 4% FBS to permit cell attachment, washed, and
      incubated for up to 3 weeks in one of the following: modified Eagle's Minimum
      Essential Medium (Opti-MEM-I) alone; Opti-MEM-I plus EGF, NGF, PDGF-BB, bovine
      pituitary extract, or FBS; or a combination of factors. At various times after
      seeding, cell numbers were determined by electronic cell counter. For each
      condition, three separate wells were tested and each sample was counted three
      times. Studies were repeated at least twice using cells from different donors and
      age groups. Within each study, a one-way ANOVA test was performed to analyze
      statistical significance. RESULTS: Cells stained positively with antibody 9.3.E,
      indicating isolation of HCEC and lack of contamination with epithelial cells or
      keratocytes. Positive staining of Ki67, indicating cycling cells, was found in
      subconfluent cultures. Plasma membrane-associated ZO-1 staining and lack of Ki67
      staining indicated that cultured cells formed a contact-inhibited monolayer.
      Cultured cells decreased in density, increased in size, and became more
      heterogeneous depending on donor age and on the number of passages. Incubation in
      OptiMEM-I promoted attachment and induced a moderate proliferative response above
      that of MEM (P < 0.001). In general, proliferative responses to growth stimuli
      were relatively slow, with cell counts generally plateauing 10 to 14 days after
      exposure to growth-promoting agents. EGF yielded a broad, dose-dependent effect
      and, at 5-50 ng/mL, peak cell counts were significantly higher (P < 0.001) than
      basal levels. EGF consistently stimulated proliferation in cells from younger
      donors, but was less effective in stimulating growth of cells from older donors.
      NGF did not show a consistent significant stimulatory effect at any concentration
      tested. PDGF-BB (25 ng/mL) tended to stimulate growth to a greater extent than
      EGF (P < 0.05) in cultures from the same donor. Pituitary extract significantly
      increased counts at 1.0 (P < 0.05) to 100 ug/mL (P < 0.001). PDGF-BB plus
      pituitary extract demonstrated greater stimulation than pituitary extract (P <
      0.01) or PDGF-BB alone (P < 0.01). FBS (1%-8%) increased cell numbers in a dose
      dependent manner, and, at 4%-8%, yielded counts significantly higher (P < 0.001)
      than that of any single growth-promoting agent tested. CONCLUSIONS: HCEC from
      both young and older donors can proliferate in vitro in response to growth
      promoting agents. Proliferation in the presence of multiple mitogens ceased when
      confluence was reached, indicating the formation of a contact-inhibited
      monolayer. In general, cells cultured from young donors were more responsive to
      the agents tested, but the relative response of HCEC to these agents was similar,
      regardless of donor age. The relative difference in the extent of the response of
      the same cell population to different mitogens suggests that these mitogens
      induce different downstream signals. The relatively robust proliferative response
      of HCEC to FBS may involve stimulation of multiple downstream signaling pathways
      may involve stimulation of multiple downstream signaling pathways and/or induce
      more sustained downstream signaling than the other growth-promoting agents
      tested.

PMID- 15161837
TI  - Suppression of corneal neovascularization by PEDF release from human amniotic
      membranes.
AB  - PURPOSE: Human amniotic membrane (HAM) transplantation is commonly used in
      corneal surface reconstruction and is known to inhibit neovascularization of this
      tissue. The purpose of the present study is to reveal the molecular basis
      underlying antiangiogenic activity of HAM. METHODS: The effects of HAM protein on
      proliferation of vascular endothelial cells and corneal epithelial cells were
      determined by quantifying viable cells using the MTT assay. The presence of
      pigment epithelium-derived factor (PEDF) in HAM was demonstrated at the protein
      level by Western blot analysis and immunohistochemistry using a monoclonal
      antibody specific to human PEDF. The PEDF concentration was measured by a
      specific ELISA. The expression of PEDF in HAM was confirmed at the RNA level by
      RT-PCR and DNA sequencing. RESULTS: Soluble proteins from HAM inhibited
      proliferation of human umbilical vein endothelial cells and bovine retinal
      capillary endothelial cells (BRCECs) while promoting proliferation of bovine
      cornea epithelial cells. Moreover, the HAM-induced inhibition of BRCECs was
      neutralized by a specific anti-PEDF antibody. PEDF protein was identified with an
      abundance of 103.84 +/- 33.21 ng/mg of soluble proteins, which is comparable to
      that in the retina, a PEDF-rich tissue. PEDF expression was predominantly
      localized in the basement membrane of HAM. RT-PCR using specific PEDF primers
      amplified a single product from HAM RNA. The PCR product has a sequence identical
      with that of human PEDF. CONCLUSION: HAM specifically inhibits endothelial cell
      growth and thus suppresses neovascularization in the cornea. PEDF in HAM has a
      major role in eliciting this antiangiogenic activity.

PMID- 15161838
TI  - p27kip1 Antisense-induced proliferative activity of rat corneal endothelial
      cells.
AB  - PURPOSE: To determine whether antisense downregulation of p27(kip1) will overcome
      G(1)-phase arrest and promote cell cycle progression in rat corneal endothelial
      cells (CECs). METHODS: Confluent cultures of rat CECs were incubated for 24 hours
      in the presence of p27(kip1) antisense (AS) oligonucleotides (oligoS) using
      nonliposomal lipid transfection. Control cultures were incubated under one of the
      following conditions: no oligos or lipid-containing buffer, lipid-containing
      buffer alone, or lipid-containing buffer plus missense (MS) p27(kip1) oligo.
      Viability was tested by a cell-viability assay after 0, 24, 48, and 72 hours.
      After postincubation for 0, 24, 48, or 72 hours, cultures were fixed and
      immunostained for p27(kip1), to test for downregulation, or for Ki67 or BrdU, to
      detect actively cycling cells. Western blot and immunocytochemistry (ICC) studies
      were conducted to determine the effect of p27(kip1) antisense treatment on the
      relative protein level and subcellular localization of several cell cycle
      proteins, including cyclin-D1, -E, -A, and -B1; CDK2 and -4; p21(cip1); and
      p15(INK4b). Proliferation was determined by direct counting of propidium iodide
      (PI) or 4',6'-diamino-2-phenylindole (DAPI)-stained cells. RESULTS: Viability was
      not significantly affected by lipid-based oligo transfection for up to 48 hours,
      after which a decline was noted. The protein level of p27(kip1) was reduced after
      AS transfection in a time-dependent manner. Nuclear staining for p27(kip1) was
      greatly reduced in CECs incubated with AS oligo. No change in p27(kip1) levels
      was observed in controls at any time point tested. p27(kip1) AS oligo
      transfection increased cyclin-D1, -E, -A, and -B1 protein levels, and all cyclins
      were localized to the nucleus. No changes in protein level were observed for
      CDK2, CDK4, p21(cip1), or p15(INK4B). A time-dependent increase in the relative
      number of Ki67- and BrdU-positive cells was noted in CECs incubated with AS
      oligo. In contrast, no to few Ki67- or BrdU-positive cells were observed in CECs
      incubated with MS oligo or the buffer-treated control cells. The percentage
      increase in the number of cells transfected with AS oligo increased with time,
      compared with that of cells transfected with MS oligo. CONCLUSIONS: Treatment
      with p27(kip1) antisense oligonucleotides followed by postincubation in 10% FBS
      lowers endogenous p27(kip1) protein levels and promotes proliferation in
      confluent cultures of rat CECs.

PMID- 15161839
TI  - Human amniotic membrane, like corneal epithelial basement membrane, manifests the
      alpha5 chain of type IV collagen.
AB  - PURPOSE: To reexamine whether the alpha5 chain of type IV (alpha5[IV]) collagen,
      thought to be absent, is in fact present in human amniotic membrane. METHODS:
      Cryosections of human amniotic membrane obtained at Cesarean section were
      immunohistochemically examined for the presence of alpha5(IV), with or without
      inclusion of the denaturing step. Amniotic membrane was digested with collagenase
      to release the noncollagenous NC1 domain from the alpha-chain. The NC1 domain of
      alpha5(IV) was then assayed on Western blot analysis. Identical experiments were
      performed with human corneas and conjunctivae obtained from an American eye bank.
      RESULTS: The basement membrane of denatured samples of amniotic membrane and
      cornea stained positive for alpha5(IV). Without the denaturing step, only corneal
      samples were positive. With or without denaturing, conjunctival epithelium did
      not stain. Western blot analysis detected NC1 domains of alpha5(IV) in amniotic
      membrane and corneal samples. CONCLUSIONS: The basement membrane of amniotic
      membrane resembles that of corneal epithelium but not conjunctiva. Amniotic
      membrane may be an excellent substrate for corneal epithelial cells.

PMID- 15161840
TI  - A mouse model for the study of recurrent corneal epithelial erosions: alpha9beta1
      integrin implicated in progression of the disease.
AB  - PURPOSE: To describe an in vivo mouse model for the study of recurrent corneal
      erosion syndrome (RCES) in mice and to characterize the changes in alpha9
      integrin expression during wound healing. METHODS: Corneal epithelial debridement
      wounds of two sizes (1.5 and 2.5 mm) were made on the ocular surface of BALB/c
      mice and were evaluated at various times after wounding. Corneas were processed
      either as whole mounts and stained with propidium iodide and an antibody against
      alpha9 integrin or for bromodeoxyuridine analyses of cell proliferation. A
      separate study involved analyses of corneal wound healing over time in individual
      mice with large and small debridement wounds. Mice were anesthetized once per
      week and their corneas stained with fluorescein to assess the quality of the
      corneal epithelium. After 6 weeks, mice were killed and eyes processed for study
      by immunofluorescence in either whole mounts or frozen sections. RESULTS: Whole
      mount confocal microscopy showed open wounds on the ocular surface of mice at 1
      and 2 weeks after large wounds were created, but not after small wounds. In
      addition, alpha9 integrin was upregulated during healing, and changes were
      observed in alpha9 integrin localization at the limbus with large wounds but not
      with small wounds. Although only 1 of 16 corneas with small wounds had erosions
      at 1 and 2 weeks, 11 of 16 with large wounds had erosions. However, by 6 weeks,
      13 of 16 eyes showed signs of erosion whether wounds were small or large. With
      large wounds, RCES corneas frequently showed numerous goblet cells adjacent to a
      limbus lacking alpha9 integrin. Corneas from mice with documented RCES showed
      both retention of alpha9 integrin and tenascin-C expression at the anterior
      stromal-epithelial interface as well as impaired relocalization of alpha3beta1
      integrin to the basement membrane zone. CONCLUSIONS: These data show that
      spontaneous recurrent corneal erosions occur in a mouse model after manual
      creation of a single wound by debridement. Differences between the healing of
      small (1.5 mm) and large (2.5 mm) wounds were observed. Large wounds often
      resulted in the presence of goblet cells on the central cornea and a loss of
      alpha9 integrin at the limbus. Small wounds never showed differences in the
      localization of alpha9 integrin at the limbus, and no goblet cells were observed
      in the central cornea. More studies are needed to understand the causes of
      erosions in these mice.

PMID- 15161841
TI  - Development of a conjunctival epithelial equivalent with improved proliferative
      properties using a multistep serum-free culture system.
AB  - PURPOSE: To investigate the use of a multistep serum-free culture system in
      developing a conjunctival epithelial equivalent with improved in vitro and in
      vivo proliferative properties and to evaluate the effect of serum supplementation
      and culture conditions on the proliferative capacity of these cells. METHODS:
      Conjunctival epithelial cells were cultivated on human amniotic membrane (HAM) in
      a multistep serum-free culture system, under submerged and air-lifted conditions.
      The bromodeoxyuridine (BrdU) ELISA proliferation assay, colony-forming efficiency
      (CFE), and number of cell generations were compared with those in serum
      containing medium. The in vivo proliferative capability of the tissue-constructs
      were evaluated by xenotransplantation to SCID mice. Cultured cells were evaluated
      for the expression of keratin-4, -19, and -3, as well as MUC5AC goblet cell
      mucin. RESULTS: The epithelial cells cultivated in serum-free medium (BrdU
      absorbance, 1.91 +/- 0.08; cell generations, 25.6 +/- 4.5) were more
      proliferative than those cultivated in serum-containing medium (BrdU absorbance,
      1.06 +/- 0.08; cell generations, 12.1 +/- 3.0). The serum-free-derived epithelial
      equivalents demonstrated a significant increase in proliferation and
      stratification after transplantation. Cells that were air lifted for 6 and 12
      days had a reduced proliferative capacity in vitro and in vivo compared with
      submerged cultures. Cultured cells expressed keratin-4 and -19, and MUC5AC mRNA
      was detected by RT-PCR. Electron microscopy demonstrated a basal lamina with
      numerous hemidesmosomes. CONCLUSIONS: This is a multistep serum-free culture
      system for developing a conjunctival epithelial equivalent with improved
      proliferative and structural properties, which are crucial for enhancing graft
      survival and regeneration of the conjunctival surface after clinical
      transplantation.

PMID- 15161842
TI  - Identification of a Kv3.4 channel in corneal epithelial cells.
AB  - PURPOSE: Voltage-gated K(+) channels maintain salt and water balance and normal
      function of corneal epithelial cells. To determine their identity, Kv channel
      types were sought in cultured rabbit corneal epithelial cells and in the intact
      rat corneal epithelium. METHODS: Immunohistochemistry and Western blot analysis
      were performed to detect K(+) channels in the membrane and cell lysates of rat
      and SV-40-transformed rabbit corneal epithelial (RCE) cells, using specific
      antibodies. The whole-cell patch clamp was used to characterize the biophysical
      and pharmacologic properties of the K(+) current in RCE cells. RESULTS:
      Expressions of K(+) channel types in corneal epithelial cells were detected by
      using a panel of specific anti-K(+) channel antibodies. Western blot analysis,
      using specific anti-K(+) channel antibodies including anti-Kv1.1, -2.1, -3.1, 
      3.2, -3.4, -4.2, and -4.3, demonstrated that in corneal epithelial cells Kv3.4
      channel was highly expressed in whole-cell lysates and in cell membrane
      preparations. The anti-Kv3.4 channel antibody produced intense immunoreactivity
      in both RCE cells and rat corneal epithelium. Fluorescence immunostaining and
      avidin-biotin-peroxidase complex immunostaining confirmed localization of Kv3.4
      channels in the cell membrane of both RCE and rat corneal epithelial cells.
      Voltage depolarization-activated K(+) currents in RCE cells were inhibited by
      applications of either 4-aminopyridine (4-AP, at micromolar levels), alpha
      dendrotoxin at nanomolar levels, or blood-depressing substance-I at nanomolar
      levels. CONCLUSIONS: Biochemical and pharmacological profiles of the voltage
      gated, 4-AP-sensitive K(+) channel in rat and RCE cells resemble characteristics
      of a Kv3.4 channel, a member of the Shaw subfamily. This channel may play
      important roles in maintaining normal function of corneal epithelium.

PMID- 15161843
TI  - TAT-mediated protein transduction into human corneal epithelial cells: p15(INK4b)
      inhibits cell proliferation and stimulates cell migration.
AB  - PURPOSE: The cell cycle inhibitor p15(INK4b) has been localized in migrating
      corneal epithelial cells. In this study, TAT-fusion protein technology was used
      to transduce p15(INK4b) into human corneal epithelial cells to examine the effect
      on cell proliferation and migration. METHODS: Human p15(INK4b), obtained by RT
      PCR, was cloned into a TAT-HA vector, and the fusion protein was purified from
      bacteria transformed with the TAT-HA-p15 construct. Various dilutions of TAT-HA
      p15 were applied to primary human corneal epithelial cells to test potency. In
      addition, the effect of exposure time was examined. Cells were labeled with
      bromodeoxyuridine to detect proliferation, and indirect immunofluorescence was
      performed. Ki67 expression was also examined. To assay cell migration, human
      corneal epithelial cells were plated inside a cylinder and exposed to TAT-HA-p15.
      The cylinder was removed, the cells were allowed to spread for 2 days, and the
      area of cell coverage was calculated. TAT-HA-beta-galactosidase served as the
      control in all experiments. Finally, the extent of retinoblastoma protein
      phosphorylation was assayed by Western blot in cells cultured with and without
      TAT-HA-p15. RESULTS: TAT-HA-p15 was successfully transduced into primary human
      corneal epithelial cells. TAT-HA-p15 decreased proliferation in a concentration-
      and time-dependent manner. The migration assay showed that TAT-HA-p15 stimulated
      cell migration 1.8-fold. TAT-HA-beta-galactosidase had no effect on proliferation
      or migration. Finally, TAT-HA-p15 decreased the level of phosphorylated
      retinoblastoma protein by 4.9-fold. CONCLUSIONS: Active p15(INK4b) can be
      efficiently transduced into primary human corneal epithelial cells using TAT
      fusion protein technology. p15(INK4b) appears to be sufficient to inhibit corneal
      epithelial cell proliferation and to stimulate cell migration.

PMID- 15161844
TI  - Noncontact measurements of central corneal epithelial and flap thickness after
      laser in situ keratomileusis.
AB  - PURPOSE: To investigate the changes in the epithelium and flap after laser in
      situ keratomileusis (LASIK), when measured with optical coherence tomography
      (OCT). METHODS: Twenty-eight eyes of 14 patients (age: 39.9 +/- 8.6 years)
      underwent LASIK. The central thickness of corneal epithelium and flap were
      measured with a real-time 1310 nm OCT 1 day, 1 week, and 1 month after surgery. A
      custom software program was used to process multiple images of each eye on each
      visit. RESULTS: After surgery, the corneal epithelium changed significantly
      (ANOVA: F((3, 81)) = 12.3, P = 0.000) with not statistically significant thinning
      at one day (mean +/- SD: 57.8 +/- 5.9 micro m, P = 0.26, compared with baseline:
      59.9 +/- 5.9 micro m) and statistically significant thickening at 1 week (60.8 +/
      5.8 micro m, P = 0.04, compared with 1 day) and 1 month (64.6 +/- 6.1 micro m, P
      = 0.008 compared with all others). There were statistically significant changes
      in the corneal flap thickness (ANOVA: F((2, 54)) = 4.59, P = 0.01) with
      thickening in the intervals between 1 day (143.3 +/- 20.6 micro m) and 1 week
      (149.7 +/- 24.6 micro m, P = 0.12), and between 1 week and 1 month (152.7 +/-
      19.3 micro m, P = 0.01). There was a strong correlation (r = 0.898) between the
      difference of corneal thickness before and after surgery and predicted laser
      ablation depth. CONCLUSIONS: OCT is a useful noncontact tool for thickness
      measurements of the epithelium, flap, and total cornea. After LASIK, the
      epithelium and flap showed thickening during the study period.

PMID- 15161845
TI  - Binocular visual field changes after surgery in esotropic amblyopia.
AB  - PURPOSE: To determine binocular visual field (BVF) changes after strabismus
      surgery in children with large angle esotropia, and whether these changes can be
      predicted, using a prism to correct the preoperative angle of deviation. METHODS:
      Monocular visual field (MVF) and BVF were measured by Goldmann perimetry in
      healthy adults (n = 6) using a range of prisms. Visual fields were then measured
      in normal children (n = 19) and in children with large angle esotropic amblyopia
      (n = 28). The visual field was measured preoperatively with and without a prism
      equal to the angle of esotropia. A further evaluation was made at 2 and 18 months
      postoperatively. RESULTS: In healthy adults, prisms had no significant effect on
      the extent of MVF or BVF. There was no significant difference in the MVF in
      children with and without strabismus. There was a significant reduction in the
      BVF and in the ratio of the BVF to MVF between normal children (138 degrees,
      0.59; P = 0.01) and children with esotropic amblyopia (120 degrees, 0.57; P =
      0.02). Postoperatively, there was a significant improvement in the BVF (P =
      0.02), which was maintained at 18 months. The increase in BVF was significantly
      greater than the variation in repeat fields (P = 0.04), with 8 of 13 children
      showing an increase in the BVF above the 95% CI of the repeatability
      measurements. There was a good linear correlation between the size of the
      preoperative BVF in the presence of a prism and the postoperative BVF (r = 0.90 P
      = 0.001). CONCLUSIONS: Children with esotropic amblyopia demonstrate a
      significant reduction in their BVF. Prisms correcting the preoperative angle
      could be used to predict the potential increase in the BVF after surgery.
      Patients with a BVF/MVF approaching that found in normal children, however, may
      not show an improvement in the size of their BVF after surgery.

PMID- 15161846
TI  - Relationship between visual field sensitivity and retinal nerve fiber layer
      thickness as measured by scanning laser polarimetry.
AB  - PURPOSE: To evaluate the strength and pattern of the relationship between visual
      field (VF) sensitivity and retinal nerve fiber layer (RNFL) thickness
      measurements by scanning laser polarimetry (SLP). METHODS: Fifty-four eyes of 54
      normal subjects (age, 42 +/- 15 years; VF mean deviation [MD], -0.69 +/- 1.01 dB)
      and 51 eyes of 51 glaucoma patients (age, 66 +/- 14 years; VF MD, -6.92 +/- 5.43
      dB) were imaged with an SLP using fixed corneal compensation (FCC) and variable
      corneal compensation (VCC). VF sensitivity was recorded in the dB and the 1/L
      scales. Linear and logarithmic relationships were sought globally and in six VF
      sectors. Relationships of VF and RNFL thickness with age were sought in normal
      subjects. RESULTS: Both VF sensitivity and RNFL thickness declined with age (as
      determined by the regression slope): -0.13% (P = 0.0005) and -0.64% (P = 0.0001)
      per year for dB and 1/L VF sensitivity, respectively, and -0.25% (P = 0.003) per
      year for VCC RNFL thickness. FCC RNFL thickness was not statistically
      significantly related to age. The relationship of VF sensitivity to VCC global
      (R(2) = 0.49) and sectoral (R(2) = 0.00-0.47) RNFL thickness was greater than for
      FCC global (R(2) = 0.12) and sectoral (R(2) = 0.00-0.21) RNFL thickness.
      Relationships were curvilinear with the dB scale, with logarithmic regression of
      dB VF sensitivity against RNFL thickness being significantly better than linear
      regression. Logarithmic regression of 1/L VF sensitivity against RNFL thickness
      was no better than linear regression for all sectors. There was no relationship
      between VF sensitivity and RNFL thickness in the temporal peripapillary RNFL
      sector. CONCLUSIONS: The strength of the structure/function relationships compare
      well with previous reports in the literature. The relationships were curvilinear
      with the dB scale and linear with the 1/L scale, and were much stronger with VCC
      than with FCC RNFL thickness measurements.

PMID- 15161848
TI  - Optic nerve damage in mice with a targeted type I collagen mutation.
AB  - PURPOSE: Transgenic (Col1a1(r/r)) mice gradually develop elevated intraocular
      pressure (IOP) with open angles. The present study was undertaken to evaluate
      optic nerve axonal loss with time in these mice. METHODS: The IOP of transgenic
      (Col1a1(r/r)) mice and control wild-type (Col1a1(+/+)) mice was measured at 7,
      12, 16, 24, 36, and 54 weeks of age using a microneedle method. Transgenic
      Col1a1(r/r) and control Col1a1(+/+) mice at 24 and 54 weeks of age were randomly
      selected and their optic nerves were processed conventionally for electron
      microscopy. Optic nerve cross-sections were collected 300 micro m posterior to
      the globe. Low (200X) and high (10,000X) magnification images were collected
      systematically and were masked before analysis. For each nerve, cross-sectional
      area was measured in low magnification images, and axonal number was counted in
      high magnification images. RESULTS: Mean IOP of the transgenic Col1a1(r/r) mice
      was significantly higher than that of the control Col1a1(+/+) mice at 16, 24, 36,
      and 54 weeks by 21%, 42%, 41%, and 33% respectively (P < 0.05). The mean axonal
      density and total axonal number in the transgenic Col1a1(r/r) mice at 54 weeks of
      age (n = 10) was significantly less than those in the control Col1a1(+/+) mice at
      24 weeks (n = 5) and 54 weeks (n = 5; P = 0.0081 and P = 0.020, respectively,
      analysis of variance, P < 0.05 for pair-wise comparisons). The mean axonal
      density and total axonal number in the transgenic Col1a1(r/r) mice at 54 weeks
      also were significantly less than in the transgenic Col1a1(r/r) mice at 24 weeks
      (n = 10). Mean axonal loss between 24 and 54 weeks of age in the transgenic
      Col1a1(r/r) mice was 28.7%. CONCLUSIONS: Transgenic Col1a1(r/r) mice develop
      sustained elevation of IOP and progressive optic nerve axon loss. This suggests
      that these mice may be useful as a mouse model of primary open angle glaucoma as
      well as for assessing the relationship between collagen type I metabolism and
      optic nerve axon loss.

PMID- 15161847
TI  - Functional and structural analysis of the visual system in the rhesus monkey
      model of optic nerve head ischemia.
AB  - PURPOSE: A redistribution of neurochemicals has been identified in the visual
      cortex of monkeys with laser-induced glaucoma. Examined were functional,
      structural, and neurochemical changes to the retina, optic nerve, and central
      visual system in a nonhuman primate model of optic nerve head (ONH) ischemia
      caused by sustained unilateral administration of endothelin (ET)-1 to the optic
      nerve. METHOD: ET-1 or sham control solution was delivered by osmotic minipump to
      the retrolaminar region of one optic nerve of rhesus monkeys (Macaca mulatta) for
      1.5 years. ONH topography and blood flow velocity were serially studied with
      scanning laser tomography and laser Doppler flowmetry, respectively. Retinal and
      cortical electrophysiologic measurements from pattern-derived stimuli were
      obtained quarterly. Immunohistochemistry was used to identify the distribution of
      calbindin (CB) and c-Fos labeled neurons in the visual cortex areas V1 and V2,
      and lateral geniculate nucleus (LGN). Retinal ganglion cell counts and optic
      nerve axon density were determined by light microscopy. RESULTS: No significant
      changes in retinal and ONH morphology, ONH blood flow velocity, and retinal and
      cortical pattern-derived functional activity were detected. Measurement of CB
      positive cell density in V1 and V2 showed a significant decrease in CB labeling
      to the contralateral side of the ET-1-treated eye (P < 0.04). CB-positive cells
      were present in the magnocellular layers of the LGN with no differences noticed
      between the ET-1- and sham-treated eyes. c-Fos-labeled neurons were found in
      striate area V1 and extrastriateV2 of both groups. No c-Fos labeling was observed
      in the LGN. CONCLUSIONS: Administering ET-1 to the orbital optic nerve alters
      neuronal metabolic activity in the visual cortex in rhesus monkeys. Metabolic
      activity reductions in the visual cortex precede the ability to detect functional
      and structural alterations in the retina, ONH, and visual cortex in this animal
      model.

PMID- 15161849
TI  - Psychophysical measurement of neural adaptation abnormalities in magnocellular
      and parvocellular pathways in glaucoma.
AB  - PURPOSE: It is well established that contrast sensitivity is reduced in glaucoma.
      This study explored whether such contrast processing abnormalities consist of an
      absolute threshold level difference or a problem with contrast gain control.
      METHODS: Seventeen patients with primary open-angle glaucoma and 17 approximately
      age-matched control subjects participated. Subjects were tested foveally and
      midperipherally (12.5 degrees ). Subjects with glaucoma were tested in a
      peripheral region of relatively normal visual field (neighboring locations
      required to be within the normal 95% confidence limit on the total deviation plot
      of their most recent SITA/full threshold Humphrey Field Analyzer assessment; Carl
      Zeiss Meditec, Dublin, CA). Control subjects were tested in matching locations.
      Contrast discrimination was assessed using the steady-pedestal (magnocellular [M]
      pathway) and pulsed-pedestal (parvocellular [P] pathway) stimuli of Pokorny and
      Smith for seven pedestal luminances between 15 and 75 cd/m(2), presented on a
      background of 30 cd/m(2). RESULTS: Glaucoma group thresholds were significantly
      elevated compared with control subjects foveally and peripherally on both the
      pulsed-pedestal (P) and steady-pedestal (M) tasks (P < 0.01). Effect size
      statistics revealed slightly greater deficits on the P pathway task and greater
      deficits for pedestals that were decrements, rather than increments, from the
      surround luminance. Foveal deficits were of a magnitude to be explained by a
      reduction in contrast sensitivity; however, the peripheral deficits were greater
      than predicted by this factor alone. CONCLUSIONS: Foveal and midperipheral
      dysfunction of both M and P pathways was identified in people with glaucoma, in
      areas of relatively normal visual field performance. These findings are
      supportive of nonselective neural adaptation abnormalities in early glaucoma.

PMID- 15161850
TI  - Selective ganglion cell functional loss in rats with experimental glaucoma.
AB  - PURPOSE: To characterize retinal functional consequences of elevated intraocular
      pressure (IOP) in a rat model of experimental glaucoma. METHODS: Unilateral
      elevation of IOP was produced by hypertonic saline injection into an episcleral
      vein in 20 adult male Brown-Norway rats. IOP was measured in both eyes of awake
      animals four to five times per week. After 5 weeks, animals were dark adapted
      overnight (>12 hours) and full-field electroretinograms (ERGs) were obtained
      simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (
      6.64-2.72 log cd-s/m(2)). Photopic responses were also obtained (0.97-2.72 log cd
      s/m(2)) after 15 minutes of light adaptation (150 cd/m(2)). Eyes were processed
      the following day for histologic evaluation by light microscopy, including masked
      determination of optic nerve injury grade (ONIG; 1, normal; 5, severe, diffuse
      damage). RESULTS: Among experimental eyes, the group average IOP (+/-SD) was 34.5
      +/- 4.1 mm Hg, whereas the average for control eyes was 28.1 +/- 0.5 mm Hg (t =
      7.1, P < 0.0001). The average ONIG for experimental and control eye groups,
      respectively, was 3.4 +/- 1.7 and 1.0 +/- 0.02 (t = 6.3, P < 0.0001). The ONIG
      increased with mean IOP in experimental eyes (r(2) = 0.78, P < 0.0001) and was
      unrelated to mean IOP in control eyes (r(2) = 0.09, P = 0.18). In experimental
      eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural
      (histologic) damage to the optic nerve evident by light microscopy (ONIG = 1.1 +/
      0.2, n = 5), there was a selective reduction of the positive scotopic threshold
      response (pSTR; P < 0.001), whereas other ERG components remained unaltered. In
      four of the five eyes, pSTR amplitude was reduced by more than 50%, whereas all
      five had normal scotopic a-wave, b-wave, and OP amplitudes. Eyes with mean IOP of
      more than 35 mm Hg had reduced a-wave, b-wave, and oscillatory potential (OP)
      amplitudes. CONCLUSIONS: As demonstrated by prior studies, selective loss of the
      pSTR is indicative of selective retinal ganglion cell (RGC) injury. In this rat
      model of experimental glaucoma, selective RGC functional injury occurred before
      the onset of structural damage, as assessed by light microscopy of optic nerve
      tissue. The highest IOP levels resulted in nonselective functional loss. Thus, in
      rodent models of experimental glaucoma, lower levels of chronically elevated IOP
      may be more relevant to human primary chronic glaucoma.

PMID- 15161851
TI  - Experimental and numerical studies of adenovirus delivery to outflow tissues of
      perfused human anterior segments.
AB  - PURPOSE: To investigate the efficacy of two different methods of adenoviral
      transfer of genes to trabecular meshwork (TM) and Schlemm's canal (SC) cells in
      cultured human anterior segments, using both experimental and numerical analyses.
      METHODS: Replication-deficient adenoviruses having coding sequence for beta
      galactosidase (beta-gal) under the control of the cytomegalovirus promoter were
      used. Efficiency of gene transfer over time was verified by infecting cultured
      human TM cells and assaying for beta-gal activity. Next, ostensibly normal paired
      human eyes were prepared by standard techniques and perfused for 2 to 5 days to
      measure baseline facilities. Eyes were then infected by one of two methods:
      standard transcorneal puncture, or injection into a 1 mm diameter silastic
      segment of supply tubing immediately upstream of the perfusion dish. In both
      cases, the nominal total dose was 2 x 10(8) viral particles. Five days after
      viral injection, eyes were harvested and fixed, and wedges from each of four
      quadrants were examined histologically. Sections were assayed for beta-gal
      activity and/or stained with toluidine blue. In a parallel study, flow and viral
      transport within perfused anterior segments were numerically simulated for
      conditions that approximated those used experimentally. RESULTS: Eyes receiving
      viral particles by transcorneal injection showed variable levels of beta-gal
      activity and highly variable TM cellular morphology, ranging from excellent
      preservation to cellular lysis. Eyes receiving an equivalent viral dose via the
      supply tubing showed higher transfer efficiency, as judged by almost complete TM
      cell loss (indicative of viral toxicity) and intense extracellular beta-gal
      activity from the residual cytoplasm. At lower doses (1/3 to 1/1000 of that used
      in transcorneal injection) beta-gal activity was still present, while TM cell
      morphology was good at the lower viral doses. Computer modeling showed that the
      region beneath the cornea was nearly stagnant, and consequently virus introduced
      into this region by transcorneal injection was delivered very slowly to the TM.
      This caused the effective delivered viral dose to be low and sensitively
      dependent on the volume and shape of the transcorneally injected virus bolus.
      CONCLUSIONS: Injection of adenovirus into supply tubing led to consistent
      delivery of reporter gene and approximately 300-fold greater efficiency of gene
      transfer compared to the transcorneal injection method, and is therefore the
      preferred method for introducing viral particles into perfused anterior segments.
      These findings were consistent with computer modeling of flow and mass transport
      in perfused anterior segments. Although these quantitative results are specific
      to adenovirus, this general trend should hold for a wide range of perfused
      compounds.

PMID- 15161852
TI  - Expression of toll-like receptor 4 and its associated lipopolysaccharide receptor
      complex by resident antigen-presenting cells in the human uvea.
AB  - PURPOSE: To investigate the in vivo expression of toll-like receptor 4 (TLR4) and
      its associated lipopolysaccharide (LPS) receptor complex in the human eye.
      METHODS: Normal human ocular tissues were evaluated for in vivo TLR4, MD-2, and
      CD14 mRNA and protein expression by RT-PCR and immunohistochemistry,
      respectively. The distribution patterns and phenotypes of the cells expressing
      these proteins were further characterized by confocal microscopy and double-label
      immunofluorescence studies. RESULTS: Normal human uvea, retina, sclera, and
      conjunctiva constitutively expressed TLR4, MD-2, and CD14 mRNA. The protein
      expression of these molecules was restricted, however, to resident antigen
      presenting cells (APCs) in the normal human uvea, consisting mainly of HLA-DR(+)
      dendritic cells (DCs). These APCs endowed with the complete LPS receptor complex
      appeared to be strategically positioned in perivascular and subepithelial
      locations for surveying blood-borne or intraocular LPS. In contrast, other cell
      types of the normal human cornea, conjunctiva, retina, and sclera did not express
      TLR4/MD-2 protein in vivo as detectable by immunohistochemistry. CONCLUSIONS: The
      present study demonstrates for the first time that resident APCs in the normal
      human uvea express TLR4 and its associated LPS receptor complex. This has
      significant implications for the understanding of normal ocular immunity as well
      as unraveling the potential role of Gram-negative bacteria in the pathogenesis of
      acute anterior uveitis (AAU).

PMID- 15161853
TI  - Immune responses to retinal self-antigens in CD25(+)CD4(+) regulatory T-cell
      depleted mice.
AB  - PURPOSE: Prior work has shown that autoimmune uveoretinitis develops
      spontaneously in CD25(+)CD4(+) regulatory T-cell-depleted mice (Tr-depleted
      mice). In this study, the generation of autoantibodies and autoreactive T-cells
      specific to retinal antigens was examined in Tr-depleted mice with uveoretinitis,
      and the pathogenic and immunogenic abilities of the autoreactive T cells were
      evaluated. METHODS: Tr-depletion was achieved in (C57BL/6 x A/J) F1 (B6A) mice by
      thymectomy on day 3 of life followed by intraperitoneal injection of an anti-CD25
      mAb. At 6 months of age, autoantibodies to the retina were evaluated by indirect
      immunofluorescence, and total IgG2a levels in sera were assessed by ELISA. The
      pathogenic abilities of the splenic T cells were examined by adoptive transfer to
      syngeneic nu/nu mice, and the proliferation responses and the secretion of
      granulocyte-macrophage-colony-stimulating factor (GM-CSF), IFN-gamma, and IL-10
      on stimulation by retinal self-antigens was also evaluated. RESULTS:
      Autoantibodies to the retinal photoreceptor cell layer were detected in Tr
      depleted mice, and the titers correlated well with the grades of inflammatory
      lesions. The splenic CD4(+) T cells of Tr-depleted mice induced uveoretinitis in
      the recipients by adoptive transfer and exhibited proliferative responses and
      secretion of IFN-gamma, but not of IL-10, by in vitro stimulation with S-Ag and
      interphotoreceptor retinoid-binding protein (IRBP). Moreover, the total IgG2a
      level in serum was markedly and significantly augmented in Tr-depleted mice.
      CONCLUSIONS: The results suggest that in Tr-depleted mice in which uveoretinitis
      develops, S-Ag and IRBP-specific T cells are spontaneously sensitized and shifted
      to a Th1-phenotype. These sensitized T cells may account for the development of
      autoimmune uveoretinitis in Tr-depleted mice.

PMID- 15161854
TI  - Differential involvement of phosphoinositide 3-kinase/Akt in human RPE MCP-1 and
      IL-8 expression.
AB  - PURPOSE: To investigate the role of the phosphatidylinositol 3-kinase (PI3K)
      pathway and the signal mediator AP-1 in monocyte chemotactic protein (MCP)-1 and
      interleukin (IL)-8 gene expression in human retinal pigment epithelial (hRPE)
      cells. METHODS: hRPE cells were stimulated with IL-1beta and TNF-alpha and by
      coculturing with monocytes in the presence or absence of a series of kinase
      inhibitors. The induction of MCP-1 and IL-8 protein and mRNA was determined by
      ELISA and RT-PCR, respectively. Western blot analysis, kinase assays, and
      electrophoretic mobility shift assays were used to detect the activation of
      signaling mediators and transcription factors. RESULTS: Concomitant with the
      induction of chemokine expression by the stimuli, there was phosphorylation of
      PI3K and its downstream targets-namely, Akt, GSK, and FKHR. Ly294002, a specific
      inhibitor of PI3K, resulted in time- and dose-dependent blockade of MCP-1 mRNA
      expression and protein production. The IC(50) for inhibition of MCP-1 secretion
      induced by IL-1beta, TNF-alpha, and hRPE-monocyte binding was 16, 12, and less
      than 3 micro M, respectively. In contrast, Ly294002 did not inhibit the IL-8
      expression induced by any of the stimuli. Ly294002 as well as U0126, SB202190,
      and SP600125, the selective inhibitors of MEK, p38, and JNK, respectively,
      strongly inhibited induced c-fos expression, whereas Ly294002 did not inhibit
      induction of MEK, p38, or JNK. Blockade of PI3K/Akt abolished IL-1beta-induced
      nuclear translocation of AP-1, whereas the induction of IkappaB degradation was
      unchanged. CONCLUSIONS: The Ly294002-sensitive PI3K/Akt pathway regulates MCP-1,
      but not IL-8 expression in hRPE cells independent of MAPK and IkappaB. PI3K
      dependent induction of hRPE c-fos and AP-1 nuclear translocation may be a target
      for therapies aimed at modulating MCP-1 in retinal diseases.

PMID- 15161855
TI  - Pseudomonas aeruginosa with lasI quorum-sensing deficiency during corneal
      infection.
AB  - PURPOSE: To understand the importance of Pseudomonas aeruginosa quorum-sensing
      systems in the development of corneal infection, the genotypic characteristics
      and pathogenesis of seven ocular isolates with low-protease and acyl homoserine
      lactone (AHL) activity and quorum-sensing mutants of PAO1 deficient in lasI,
      lasR, or rhlR were investigated in the study. METHODS: The possession of the
      quorum-sensing genes lasI, lasR, rhlI, rhlR, and the quorum-sensing controlled
      genes lasB, aprA, and rhlAB in the clinical isolates were determined by
      polymerase chain reaction and Southern blot hybridization. Elastinolytic
      activity, controlled by the las system, was assayed using elastin Congo red and
      rhamnolipid production controlled by the rhl system was assessed using agar
      plates containing methylene blue/cetyltrimethyl ammonium bromide. Induction of
      keratitis was examined in a scarified inbred BALB/c mouse model. RESULTS: The
      clinical isolates Paer1 and -3 were lasI and lasR negative, and the isolates
      Paer2 and -4 were rhlR and rhlAB negative. The isolates Paer17, Paer26, 6294 and
      6206 possessed all the genes examined. There was no rhamnolipid production in
      clinical isolates Paer2 and -4. The isolates Paer1 and -3 were virtually
      avirulent in the scarified mouse corneas. Using isogenic PAO1 mutants, strain
      lasI showed a markedly reduced virulence in the corneal infection model. The
      remainder of the clinical isolates and the lasR or rhlR mutant strains caused
      severe keratitis. CONCLUSIONS: These results indicate that quorum-sensing
      deficiency may occur naturally in clinical isolates, and the possession of lasI
      and hence a functional Las quorum-sensing system may be important in development
      of corneal infection.

PMID- 15161856
TI  - Identification of 18S ribosomal DNA genotype of Acanthamoeba from patients with
      keratitis in North China.
AB  - PURPOSE: To identify the genotype of 18S ribosomal RNA gene (18S rDNA, Rns) of
      the Acanthamoeba strains isolated from patients with keratitis in northern China.
      METHODS: The genus-specific primers JDP1 and JDP2 were used for the amplification
      of the amplimer ASA.S1. With DNA PCR and sequencing, Rns genotypes were
      identified according to the DF3 sequence variances. RESULTS: Of all 26 DF3
      sequences obtained from the 26 Acanthamoeba strains, 18 were unique (69.2%). Of
      those, 17 were Rns genotype T4 and one was Rns genotype T3. CONCLUSIONS: Most
      Acanthamoeba strains isolated from keratitis in northern China were Rns genotype
      T4. The results are in agreement with recent results in the literature.

PMID- 15161857
TI  - CD95 ligand expression on corneal epithelium and endothelium influences the fates
      of orthotopic and heterotopic corneal allografts in mice.
AB  - PURPOSE: To determine the extent to which CD95 ligand (CD95L) expressed on
      corneal epithelium and endothelium influences survival of cornea grafts placed
      orthotopically and heterotopically in the anterior chamber (AC), an immune
      privileged site. METHODS: Corneas from eyes of C57BL/6 (B6) and B6.gld (CD95L
      deficient) mice were (1) rendered into small full-thickness fragments, with or
      without an epithelial layer, and placed behind recipient corneas in the ACs of
      BALB/c eyes, while BALB/c corneas were similarly implanted in eyes of B6 and
      B6.lpr (CD95 deficient) mice; or (2) corneas were grafted orthotopically in
      BALB/c eyes as intact corneas or as composite corneas in which epithelium from
      one donor source was layered in vitro onto epithelium-deprived stroma+endothelium
      from another donor source before grafting. The fate of the grafts was assessed
      clinically and histologically, and the capacity of the grafts to sensitize
      recipient mice to donor alloantigens (delayed hypersensitivity, DH) was
      evaluated. RESULTS: Allogeneic, full-thickness B6.gld corneal fragment grafts
      placed in the AC of BALB/c mice were rejected and sensitized their recipients,
      whereas epithelium-deprived B6.gld cornea fragments survived indefinitely and
      failed to sensitize their recipients. BALB/c corneal fragment grafts placed in
      the AC of C57BL/6 or B6.lpr eyes were rejected. Orthotopic cornea grafts composed
      of B6.gld epithelium layered onto wild-type B6 stroma and endothelium were
      rejected at a tempo and incidence similar to full-thickness B6 grafts, whereas
      orthotopic composite cornea grafts containing B6 epithelium layered onto B6.gld
      stroma+endothelium were vigorously rejected. CONCLUSIONS: CD95L expression on
      epithelium of full-thickness cornea fragment grafts placed in the anterior
      chamber of BALB/c eyes protects these heterotopic grafts from rejection but has
      only a trivial role to play in determining the fate of orthotopic corneal grafts.
      In the latter type of corneal grafts, CD95L expression on the endothelium plays
      an essential role in preventing graft rejection.

PMID- 15161858
TI  - Metabolic changes in rat lens after in vivo exposure to ultraviolet irradiation:
      measurements by high resolution MAS 1H NMR spectroscopy.
AB  - PURPOSE: In the present study, high-resolution magic angle spinning proton
      nuclear magnetic resonance (HR-MAS (1)H NMR) spectroscopy was used to investigate
      changes in the metabolic profile of intact rat lenses after UVB irradiation of
      the eyes. METHODS: Three groups of Sprague-Dawley rats were exposed to UVB
      radiation at 2.5, 5.0, and 7.5 kJ/m(2). One eye was exposed, and the
      contralateral eye served as the control. One week after exposure, the lenses were
      removed and forward light-scattering was quantified. Thereafter, proton NMR
      spectra from the intact lenses were obtained. Relative changes in metabolite
      concentrations were determined. RESULTS: The lenses in all three groups showed
      significant increases in light-scattering after UVB irradiation. The high-quality
      HR-MAS (1)H NMR spectra permitted more than 30 different metabolites to be
      identified. UVB irradiation caused a significant decrease (P < 0.05) in
      concentrations of taurine, hypotaurine, tyrosine, phenylalanine, valine, myo
      inositol, phosphocholine, betaine, succinate, and glutathione at all three UV
      doses. For glycine, glutamate, and lactate, significant decreases in
      concentration were observed at the two lowest UVR-B doses. The total amount of
      adenosine tri- and diphosphate and (ATP, ADP) decreased significantly and that of
      adenosine monophosphate AMP increased significantly at the two highest doses.
      Alanine was the only amino acid that increased after UVB irradiation. None of
      these metabolites exhibited a significant UVB dose-dependent relationship.
      CONCLUSIONS: This study demonstrates for the first time the potential of HR-MAS
      (1)H NMR spectroscopy as an analytical tool for use on intact lenses. Near
      threshold UVR-B doses led to a generally significant decrease in water-soluble
      metabolites 1 week after exposure. The lack of dose-dependent changes in the
      metabolites indicates that repair processes during the first week after UVB
      irradiation overcome the immediate metabolic disturbances.

PMID- 15161859
TI  - Quantitative trait locus mapping for age-related cataract severity and synechia
      prevalence using four-way cross mice.
AB  - PURPOSE: The goal of this study was to map mouse quantitative trait loci (QTL)
      that influence the development of murine age-related cataract and synechia, by
      using a genetically heterogeneous mouse population bred by a four-way cross.
      METHODS: The test population consisted initially of 510 mice bred as the progeny
      of (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males. Each mouse was
      examined by slit lamp at 18 and 24 months of age and scored for degree of lens
      opacity on a 0 to 4+ scale, and the presence or absence of additional anterior
      chamber disease was noted. The presence of synechia was confirmed by histology.
      Each mouse was genotyped at 96 maternal and 92 paternal loci, and the
      significance of association between genotype and eye lesions was tested by
      permutation analysis. RESULTS: Significant QTL with effects on lens opacity at 24
      months were detected on mouse chromosomes 4, 11, and 12. The effects were
      additive, and severe cataracts were seen in 80% of the mice with all three high
      risk alleles, but in only 28% of the mice with all three low-risk alleles. The
      risk of synechia was associated with paternal chromosome 1 and on both the
      maternal and paternally inherited chromosome 4. Mice with all three high-risk
      alleles had a 68% risk of synechia, compared with a 0% incidence in mice with all
      three counteralleles. CONCLUSIONS: A four-way cross population of mice can be
      used to map polymorphic loci that influence cataract severity and synechia
      prevalence in late life. The results provide a first step toward identification
      of the individual genes involved and may help to guide the search for homologous
      human genes.

PMID- 15161860
TI  - Insertion of a Pax6 consensus binding site into the alphaA-crystallin promoter
      acts as a lens epithelial cell enhancer in transgenic mice.
AB  - PURPOSE: Although the murine alphaA-crystallin promoter is the most commonly used
      promoter for achieving transgene expression in the developing lens, this promoter
      directs transgene expression efficiently only in lens fiber cells. The purpose of
      the present study was to generate promoters capable of directing transgene
      expression to the entire lens but not to the corneal epithelium. METHODS:
      Transgenic mice were generated with fragments of the murine alphaA- and alphaB
      crystallin promoters, as well as with an alphaA-crystallin promoter engineered
      with the insertion of a Pax6 consensus binding site driving either human growth
      hormone (hGH) or Cre recombinase genes. hGH expression was evaluated by in situ
      hybridization and immunohistochemistry. Cre expression was revealed by x-gal
      staining after crossing Cre transgenic mice with a Cre reporter strain. RESULTS:
      Within the lens, the -214/+38 alphaB-crystallin promoter fragment directed
      transgene expression in the lens epithelium, but not in fiber cells. The native 
      282/+43 alphaA-crystallin promoter drove transgene expression in the lens fiber
      cells of several independent lines of transgenic mice, but none of these mice
      demonstrated significant transgene expression in the lens epithelium. In
      contrast, the insertion of a 32-bp sequence containing a Pax6 consensus binding
      site into the -282/+43 alphaA-crystallin promoter reproducibly led to transgene
      expression in the lens epithelium as well as the lens fiber cells. CONCLUSIONS:
      The inclusion of a Pax6 consensus binding site within the -282/+43 alphaA
      crystallin promoter enhances the ability of this promoter to drive transgene
      expression in the lens epithelium.

PMID- 15161861
TI  - A nonsense mutation in the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2):
      association with autosomal recessive congenital cataracts.
AB  - PURPOSE: To identify the genetic defect associated with autosomal recessive
      congenital cataract in four Arab families from Israel. METHODS: Genotyping was
      performed using microsatellite markers spaced at approximately 10 cM intervals.
      Two-point lod scores were calculated using MLINK of the LINKAGE program package.
      Mutation analysis of the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2) gene
      was performed by direct sequencing of PCR-amplified exons. RESULTS: The cataract
      locus was mapped to a 13.0-cM interval between D6S470 and D6S289 on Chr. 6p24. A
      maximum two-point lod score of 8.75 at theta = 0.019 was obtained with marker
      D6S470. Sequencing exons of the GCNT2 gene, mutations of which have been
      associated with cataracts and the i blood group phenotype, revealed in these
      families a homozygous G-->A substitution in base 58 of exon-2, resulting in the
      formation of premature stop codons W328X, W326X, and W328X, of the GCNT2A, -B,
      and -C isoforms, respectively. Subsequent blood typing of affected family members
      confirmed the possession of the rare adult i blood group phenotype. CONCLUSIONS:
      A nonsense mutation in the GCNT2 gene isoforms is associated with autosomal
      recessive congenital cataract in four distantly related Arab families from
      Israel. These findings provide further insight into the dual role of the I
      branching GCNT2 gene in the lens and in reticulocytes.

PMID- 15161862
TI  - Aberrant lens fiber differentiation in anterior subcapsular cataract formation: a
      process dependent on reduced levels of Pax6.
AB  - PURPOSE: TGFbeta can induce development in lenses of opaque subcapsular fibrotic
      plaques that have many features of human subcapsular cataracts. To understand
      further the events associated with the onset and progression of TGFbeta-induced
      cataract, several different models for anterior subcapsular cataract (ASC) were
      used and characterized. METHODS: Anterior subcapsular plaques were induced in rat
      lenses cultured with TGFbeta and in transgenic mice overexpressing TGFbeta in the
      lens. ASC was also examined in lenses of mice haploinsufficient for Pax6, as well
      as in human biopsy specimens. Immunofluorescence and in situ hybridization
      labeling were used to examine changes in patterns of gene expression associated
      with cataract formation in these models. RESULTS: Examination of TGFbeta-induced
      cataract in transgenic mice established that the subcapsular plaques are composed
      of a heterogenous cell population: a population of myofibroblastic cells as well
      as a population of lens-fiber-like cells. Further support for phenotypic change
      comes from the observation that the cells in these plaques no longer expressed
      lens epithelial markers, such as Pax6 and Connexin43. Subsequent examination of
      human biopsy specimens of ASC, as well as lenses from Pax6-deficient mice, showed
      that the anterior subcapsular plaques in both cases were also composed of a
      heterogenous population of cells. In contrast, anterior subcapsular plaques that
      developed in vitro in response to TGFbeta did not have this same cellular
      heterogeneity, as no fiber-like cells were present. CONCLUSIONS: These findings
      suggest that in vivo, during TGFbeta-induced cataract formation, some lens
      epithelial cells transform into myofibroblastic cells, whereas others
      differentiate into fiber cells. As this pathologic change is accompanied by
      altered expression of genes characteristic of the normal lens epithelial cell
      phenotype and as lenses from Pax6-deficient mice exhibit development of anterior
      subcapsular plaques closely resembling those induced by TGFbeta in transgenic
      mice, the authors propose that a reduction in Pax6 levels may be essential for
      this pathologic process to progress. Furthermore, it is clear from these in vitro
      studies that TGFbeta alone cannot reproduce the same morphologic and molecular
      changes associated with ASC formation in vivo, indicating that additional
      molecule(s) in the eye are important in this process.

PMID- 15161863
TI  - Analysis of choriocapillaris flow patterns by continuous laser-targeted
      angiography in monkeys.
AB  - PURPOSE: To investigate choriocapillaris flow patterns and its segmental
      distribution in monkeys by continuous laser-targeted angiography (LTA). METHODS:
      A slit lamp was modified to incorporate two kinds of lasers (argon and diode).
      Carboxyfluorescein (CF) was encapsulated in heat-sensitive liposomes and injected
      intravenously. Encapsulated CF was released locally by applying a continuous heat
      beam provided by the diode laser (810 nm). Video angiograms were generated with
      excitation illumination provided by the argon laser (488 and 514 nm), to observe
      selective images of the choriocapillaris. RESULTS: Continuous application of the
      diode laser disclosed three distinct phases (filling, plateau, and draining) of
      fluorescent images of the choriocapillaris. In the plateau phase, a cluster of
      lobules fed by a common arteriole was uniformly illuminated. This defined area
      did not change in size while a continuous diode laser was applied to the same
      spot. Only in posterior regions did the angiograms demonstrate that during the
      filling and draining phases each lobule was filled from a central spot and
      drained along a peripheral ring, showing honeycomb flow patterns. In peripheral
      regions, large choroidal vessels as well as choriocapillaris were observed.
      CONCLUSIONS: Continuous LTA demonstrated clusters of lobules fed by a common
      arteriole, and each cluster was found to be functionally independent. There were
      regional differences in choriocapillaris flow patterns, which suggests that the
      choriocapillaris provides a more highly efficient system of outflow in posterior
      regions than in peripheral regions. This modified LTA method appears to be useful
      in analyzing choroidal circulation in vivo.

PMID- 15161864
TI  - Retinal microvascular surgery: a feasibility study.
AB  - PURPOSE: To evaluate the feasibility of microvascular surgery at the level of the
      retinal vasculature. METHOD: Porcine eyes were used, and eyecups were prepared
      under an operating microscope. Several classic microvascular maneuvers were
      explored, such as vascular puncturing, catheterization, mobilization,
      intravascular injections, and various combinations of the same. Instruments used
      ranged from disposable 30-gauge needles to an Er:YAG laser. Commercially
      available 10-0 nylon sutures, fine polyimide tubes, and custom-made fine glass
      tubes were used for vascular catheterization. RESULTS: Puncturing, mobilization,
      catheterization, and intravascular injection of retinal arteries and veins were
      possible. The connection of two remote retinal vessels with a fine tube was also
      achieved with the combination of these maneuvers. CONCLUSIONS: The feasibility of
      performing several microvascular maneuvers on retinal arteries and veins was
      demonstrated in porcine eyes. Further experimentation and development of these
      findings in a living animal model could lead to the development of such
      microvascular maneuvers in humans.

PMID- 15161865
TI  - Subthreshold transpupillary thermotherapy reduces experimental choroidal
      neovascularization in the mouse without collateral damage to the neural retina.
AB  - PURPOSE: Transpupillary thermotherapy (TTT) is currently being evaluated for
      treatment of choroidal neovascularization (CNV) in age-related macular
      degeneration. To optimize TTT for CNV, the effect was analyzed of invisible
      (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and
      on experimental CNV. METHODS: TTT was delivered to the normal retina of 42 mice
      with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain
      thermal lesions ranging from invisible (subthreshold) to visible (threshold)
      burns. CNV was induced in 53 mice by krypton laser photocoagulation of the
      fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW).
      Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV
      complex was evaluated on hematoxylin-eosin stained serial sections by measuring
      the maximum height of the CNV lesions. Ultrastructural changes were examined by
      transmission electron microscopy. RESULTS: Increasing the TTT laser power yielded
      gradually more visible effects. At 50 mW, which induced subthreshold burns, no
      damage was seen in the neural retina, retinal pigment epithelium (RPE), or
      choroid at any time point. By contrast, eyes treated with higher power exhibited
      progressively more damage to the neural retina, including a complete disruption
      of the outer nuclear layer. When TTT was applied to the laser-induced CNV
      lesions, the height of lesions was significantly reduced (P < 0.001) in response
      to all three power settings at 7 days after treatment. The mean relative
      thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT
      treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power
      settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed
      no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer
      disruption occurred with a power of 80 mW. Electron microscopy confirmed the
      presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT.
      CONCLUSIONS: Subthreshold TTT can effectively occlude newly formed vessels and
      cause regression of the experimental CNV complex without damaging the neural
      retina. The results demonstrate the importance of using subthreshold laser power
      in experimental and clinical evaluation of TTT.

PMID- 15161866
TI  - Progressive cone dystrophy associated with mutation in CNGB3.
AB  - PURPOSE: To determine the molecular basis for phenotypic variability in a three
      generation consanguineous family containing a single individual with complete
      achromatopsia and three individuals with progressive cone dystrophy. METHODS:
      Four affected individuals underwent ophthalmic examination, electrophysiological
      assessment, color fundus photography, and psychophysical testing. Blood samples
      were obtained for DNA extraction and mutation screening of the cone-specific cGMP
      gated (CNG) channel protein gene CNGB3 was undertaken. RESULTS: The clinical
      findings in one family member were consistent with a diagnosis of complete
      achromatopsia, with nystagmus, photophobia, and poor visual acuity from early
      infancy and complete color-blindness, normal fundi, and absent cone responses
      with normal rod responses on electroretinography (ERG). Mutation analysis
      revealed her to be homozygous for the common CNGB3 achromatopsia mutation,
      1148delC (Thr383fs). In contrast, the three other symptomatic individuals in the
      family had findings consistent with progressive cone dystrophy. Their visual
      problems began later in childhood (ranging from 3 to 14 years of age) and there
      was evidence of progressive deterioration in cone function. All three had a
      marked tritanopic color vision defect and fundoscopy revealed bilateral macular
      atrophy. Electrophysiological testing of these three subjects demonstrated clear
      evidence of progressive deterioration of cone responses over time; rod responses
      were normal. All three individuals with this progressive phenotype were found to
      be compound heterozygotes for the 1148delC (Thr383fs) frameshift mutation and a
      novel Arg403Gln missense mutation in CNGB3. CONCLUSIONS: Mutations in CNGB3,
      which have been shown to cause achromatopsia, are now shown to be associated with
      autosomal recessive progressive cone dystrophy. In this study, a novel Arg403Gln
      mutation was identified, located in the middle of the pore domain of the cone CNG
      cation channel beta-subunit, which when associated with the nonsense mutation
      Thr383fs, resulted in progressive cone dystrophy.

PMID- 15161868
TI  - Transplantation of transduced retinal pigment epithelium in rats.
AB  - PURPOSE: To examine the effects of transplanting retinal pigment epithelial (RPE)
      cells transduced with neurotrophic factor genes into the subretinal space of
      rats. METHODS: RPE cells were transduced with plasmids carrying the cDNAs of
      Axokine (ciliary neurotrophic factor [CNTF]; Sumitomo Pharmaceuticals Co., Ltd.,
      Tokyo, Japan), brain derived-neurotrophic factor (BDNF), and basic fibroblast
      growth factor (bFGF) genes. These RPE cells were transplanted into the subretinal
      space of rats, and the localization was examined. The expression of enhanced
      green fluorescent protein (eGFP)-BDNF-transduced RPE in the subretinal space was
      examined by real-time polymerase chain reaction (PCR) after the transplanted
      cells were collected by cell sorting. The expression of major histocompatibility
      complex (MHC) class I and -II after gene transduction was examined by real-time
      PCR. The ratio of CD4(+) and CD8(+) T cells and antibody production against
      transplanted cells were analyzed by flow cytometry. RESULTS: The transplant sites
      were not significantly different among the neurotrophic factors tested. The RPE
      cells expressed the BDNF gene in the subretinal region at approximately the same
      level as that in vitro. RPE cells transduced with Axokine stimulated MHC-I
      expression, and the cell transplantation changed the ratio of CD4(+) and CD8(+) T
      cells. A significant production of antibody against the Axokine-transduced RPE
      cells was also observed after Axokine-transduced RPE transplantation.
      CONCLUSIONS: RPE cells transduced with neurotrophic factors express the factors
      after transplantation into the subretinal space. RPE transduced with Axokine or
      bFGF, in contrast to RPE transduced with BDNF, stimulate an immunologic reaction
      of the host.

PMID- 15161867
TI  - Effect of dicarbonyl modification of fibronectin on retinal capillary pericytes.
AB  - PURPOSE: To determine effects of alpha-dicarbonyl modification of an
      extracellular matrix protein on retinal capillary pericyte attachment and
      viability. METHODS: Primary cultures of bovine retinal pericytes (BRPs) were
      seeded on either normal fibronectin (FN) or FN modified by methylglyoxal (MGO)
      and glyoxal (GO). Apoptosis was measured by flow cytometry along with caspase-3
      activity. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and
      Akt/PKB were evaluated by Western blot analysis. Cellular glutathione and
      reactive oxygen species were measured. alphaB-crystallin was measured by Western
      blot analysis and, to determine its role in apoptosis, experiments were conducted
      using BRPs that were transiently transfected with alphaB-crystallin. RESULTS:
      Cultures seeded on MGO- or GO-modified FN showed a significant reduction in the
      number of viable cells, an increase in the number of apoptotic cells, and
      increased caspase-3 activity, which correlated with the extent of FN
      modification. Pericytes seeded on either type of modified FN showed
      phosphorylation of p38 MAPK and dephosphorylation of Akt/PKB. Cultures seeded on
      dicarbonyl-modified FN had reduced glutathione and increased levels of reactive
      oxygen species compared with those on a normal matrix. Cells on the altered
      matrices had reduced alphaB-crystallin levels as well. Transient transfection of
      rat alphaB-crystallin into BRPs significantly reduced the apoptosis triggered by
      alpha-dicarbonyl-modified FN. CONCLUSIONS: These observations indicate that
      modification of FN by alpha-dicarbonyl compounds triggers apoptosis through a
      combination of increased oxidative stress and reduction of alphaB-crystallin.
      This mechanism may contribute to loss of pericytes in diabetic retinopathy and
      contribute to the resultant vascular lesions.

PMID- 15161869
TI  - Photoreceptor degeneration and loss of retinal function in the C57BL/6-C2J mouse.
AB  - PURPOSE: The C57BL/6-c(2J) (c2J) mouse strain has been shown in earlier studies
      to be highly resistant to light damage. Subsequent studies related this
      resistance to an amino acid substitution (leu450met) in a pigment epithelial
      enzyme (RPE65), which slowed the rate of rhodopsin regeneration. The present
      study was conducted to examine patterns of photoreceptor death,
      electrophysiological function (the ERG) and trophic factor expression over the
      life of the C57BL/6-c(2J) retina. METHODS: Observations were made on two C57BL/6J
      c(2J) substrains, one albino (Tyr/Tyr) and one pigmented (Tyr/(+)), and two
      nondegenerative strains, one albino (BALB/cJ) and one pigmented (C57BL/6J). Mice
      were raised in dim cyclic light (12 hours at 5 lux, 12 hours in the dark), and a
      developmental series of retinas of each strain was taken between postnatal day
      (P)4 and (P365(+)). Retinas were examined for cell death by using the TUNEL
      technique, stress-induced protein expression (FGF-2 and GFAP), and measures of
      retinal thickness. The dark-adapted ERG was recorded in dark-adapted conditions
      in early adulthood (13-15 weeks) and late adulthood (>1 year). RESULTS: In both
      C57BL/6-c(2J) substrains, the retina showed marked degenerative features when
      compared with two control strains, BALB/cJ (leucine at codon 450 in RPE65) and
      C57BL/6J (methionine). During development and into young adulthood, photoreceptor
      death rates were abnormally high, levels of two stress-inducible proteins (FGF-2
      and GFAP) were abnormally high, and the ERG (electroretinogram) was significantly
      reduced in amplitude (<50% of values in BALB/cJ or C57BL/6J). The rate of
      photoreceptor death remained abnormally high into young adulthood (2-3 months)
      but decreased to control levels by 1 year. Accordingly, the thickness of the
      outer nuclear layer and the ERG were stable over the same period. CONCLUSIONS:
      Results suggest that a still-unidentified stress increases photoreceptor death in
      the C57BL/6-c(2J) retina during the critical period of photoreceptor development
      and into young adulthood, upregulates stress-inducible factors, and markedly
      limits the amplitude of the ERG. These degenerative changes do not continue after
      early adulthood, the retina remaining stable in structure and function into late
      adulthood. The degenerative changes were apparent in both albino and pigmented
      C57BL/6-c(2J) substrains. Their genetic cause remains unknown.

PMID- 15161870
TI  - Photoreceptor death, trophic factor expression, retinal oxygen status, and
      photoreceptor function in the P23H rat.
AB  - PURPOSE: To relate the oxygen environment of the retina to photoreceptor
      stability, protection, and function in the P23H rat. METHODS: Heterozygote P23H-3
      (Line 3) rats were studied. Photoreceptor death rates were assessed with the
      TUNEL technique for detection of fragmenting DNA, in a developmental series from
      postnatal day (P)16 to P105 (adult). In adult retinas, trophic factor status was
      assessed with immunohistochemistry, intraretinal oxygen environment with O(2)
      sensing electrodes, and photoreceptor function by the flash-evoked, dark-adapted
      electroretinogram (ERG), recorded in anesthetized animals. RESULTS: Photoreceptor
      death begins by P16; peaks at P25, when the frequency of TUNEL(+) profiles
      exceeds 70/mm of retina; and then declines to low (<5/mm) adult rates. Compared
      with that in nondegenerative Sprague-Dawley (SD) rats, the rate of photoreceptor
      death is abnormally high from P16 and remains several-fold higher than normal
      into young adulthood. In addition, the outer nuclear layer is reduced to
      approximately half of control thickness, and the levels of ciliary neurotrophic
      factor (CNTF), glial fibrillary acidic protein (GFAP), fibroblast growth factor
      (FGF)-2, and FGF-2/FGFR1 colocalization are markedly upregulated. O(2) tension
      and uptake are relatively normal in the inner retina, but uptake is considerably
      reduced, and O(2) tension is significantly raised in the outer retina. Surviving
      photoreceptors generate an a-wave with normal peak latency but sharply reduced
      amplitude. CONCLUSIONS: Excess photoreceptor degeneration in the P23H-3 retina
      begins just after eye opening, peaks in early postnatal life, and then slows, but
      persists into adulthood. In the adult retina, surviving photoreceptors operate in
      an environment that is chronically hyperoxic (and therefore toxic) and in which
      protective factors (CNTF, FGF-2) are chronically upregulated. The net result,
      slow degeneration and degraded function in an environment that is both toxic and
      protective, may be representative of adult photoreceptor status in a number of
      human retinal degenerations. Hyperoxia-induced photoreceptor death may be a self
      reinforcing factor that increases oxidative stress in surviving photoreceptors.

PMID- 15161871
TI  - Astrocyte-endothelial cell relationships during human retinal vascular
      development.
AB  - PURPOSE: To evaluate evidence for the presence of vascular precursor cells
      (angioblasts) and astrocyte precursor cells (APCs) in the developing human retina
      and determine their relationship. METHODS: Pax-2/GFAP/CD-34 triple-label
      immunohistochemistry was applied to four retinas aged 12, 14, 16, and 20 weeks of
      gestation (WG) to label APCs, astrocytes, and patent blood vessels. APCs are Pax
      2(+)/GFAP(-), whereas astrocytes are Pax-2(+)/GFAP(+). Adenosine diphosphatase
      (ADPase) enzyme histochemistry, which identifies endothelial cells and vascular
      precursors, was applied to human retinas aged 12, 16, 17, and 19 WG. Nissl stain,
      a nonspecific cell soma marker, was applied to 14.5-, 18-, and 21-WG retinas.
      Established blood vessels were visualized with CD34 and ADPase. RESULTS:
      Topographical analysis of the distribution of Nissl-stained spindle cells and
      ADPase(+) vascular cells showed that these two populations have similar
      distributions at corresponding ages. ADPase(+) vascular precursor cells preceded
      the leading edge of patent vessels by more than 1 millimeter. In contrast, Pax
      2(+)/GFAP(-) APCs preceded the leading edge of CD34(+) blood vessels by a very
      small margin, and committed astrocytes (Pax-2(+)/GFAP(+)) were associated with
      formed vessels and nerve fiber bundles. Two populations of ADPase(+) cells were
      evident, a spindle-shaped population located superficially and a deeper spherical
      population. The outer limits of these populations remain static with maturation.
      CONCLUSIONS: A combination of Pax-2/GFAP/CD34 immunohistochemistry, Nissl
      staining, and ADPase histochemistry showed that the vascular precursor cells
      (angioblasts), identified using ADPase and Nissl, represent a population distinct
      from Pax-2(+)/GFAP(-) APCs in the human retina. These results lead to the
      conclusion that formation of the initial human retinal vasculature takes place
      through vasculogenesis from the prior invasion of vascular precursor cells.

PMID- 15161872
TI  - Expression of LRP1 in retinal pigment epithelial cells and its regulation by
      growth factors.
AB  - PURPOSE: The retinal pigment epithelial (RPE) cells are mitotically inactive
      under normal conditions, but play a pivotal role in the pathogenesis of
      proliferative vitreoretinopathy (PVR). Triggered by changes in the concentrations
      of growth factors, RPE cells reenter the cell cycle, proliferate, and migrate
      onto the retinal surface, into the subretinal space, and into the vitreous. The
      receptor for alpha(2)-macroglobulin (low-density lipoprotein receptor-related
      protein [LRP1], or CD91) is known to be involved in the processes of cell
      migration and invasion, as well as in the regulation of growth factor
      homeostasis. The purpose of this study was to investigate the expression of this
      receptor and its regulation, at the protein and mRNA levels, in human (h)RPE
      cells. METHODS: The cell surface expression of the receptor was studied by
      immunocytochemistry and flow cytometry. The endocytosis-related activity of LRP1
      in hRPE cells was examined by assessing the uptake of FITC-labeled, methylamine
      (MA)-treated alpha(2)-M (alpha(2)-M-MA). LRP1 mRNA expression was analyzed by
      means of the RNase protection assay (RPA) after the hRPE cells were stimulated
      with the growth factors TGF-beta1, TGF-beta2, PDGF, VEGF (each 10 ng/mL), or bFGF
      (5 ng/mL). RESULTS: hRPE cells expressed LRP1 on their cell surface. The receptor
      mediated rapid binding and endocytosis of FITC-labeled alpha(2)-M-MA. The
      expression of LRP1 mRNA strongly increased on stimulation of the cells with TGF
      beta1, TGF-beta2, or VEGF, whereas PDGF or bFGF elicited only minor effects.
      CONCLUSIONS: The expression of functionally active LRP1 in hRPE cells suggests
      that the receptor may be involved in cell migration and invasion, as reported for
      other LRP1-expressing cells. Thus, certain growth factors may control RPE cell
      migration and invasion in vivo through a regulation of LRP1 expression. As LRP1
      mediates the clearance of alpha(2)-M, known to regulate the homeostasis of many
      cytokines and growth factors, this receptor may be a promising target for
      therapeutic intervention in PVR.

PMID- 15161873
TI  - Morphological characterization of the retina of the CNGA3(-/-)Rho(-/-) mutant
      mouse lacking functional cones and rods.
AB  - PURPOSE: To assess the structural changes in the retina caused by a functional
      blockade of rods and cones and to document the time course of their degeneration.
      METHODS: Double knockout mice were generated by cross-breeding CNGA3(-/-) mice
      with Rho(-/-) mice. Retinas of mutant and wild-type mice from 3 weeks up to 12
      months of age were studied by confocal light and electron microscopy. The retinas
      were immunostained with cell-type-specific markers and with antibodies against
      synapse-associated proteins and transmitter receptors. RESULTS: In 3-week-old
      CNGA3(-/-)Rho(-/-) mice, retinal layers showed normal structural organization,
      and photoreceptors established normal synaptic contacts. Until postnatal week
      (Pw)7, presynaptic markers and postsynaptic glutamate receptors were well
      expressed at the photoreceptor terminals. Photoreceptor degeneration started at
      Pw4, progressing to an almost complete loss by 3 months. Rod spherules showed an
      increase in the number of synaptic ribbons and postsynaptic elements during this
      early stage of degeneration, and horizontal cell processes grew into the outer
      nuclear layer. At later stages of retinal degeneration, the inner plexiform layer
      (IPL) was also affected. Rod bipolar cell axon terminals showed morphologic
      alterations, but the stratification pattern of cone bipolar cell axons and
      amacrine cell processes appeared unaffected. Transmitter receptors (GlyRalpha3,
      GABA(A) alpha2, GluR2/3) showed no obvious changes in the distribution and
      density of their synaptic clusters throughout the IPL at postnatal month 12.
      CONCLUSIONS: The normal structural and synaptic organization of the mutant retina
      at Pw3 suggests that photoreceptor light responses are not essential for the
      development of the retinal circuitry. However, functional photoreceptors are
      necessary for the maintenance of rods and cones and their contacts in the OPL,
      because they degenerate almost completely by 3 months after birth. Degenerative
      changes can also be observed in the IPL; however, they appear to have a slower
      time course and by 12 months of age the IPL circuitry appears to be surprisingly
      intact.

PMID- 15161874
TI  - A piece of my mind. Twilight on North Second.

PMID- 15161875
TI  - Promoting adequate sleep finds a place on the public health agenda.

PMID- 15161876
TI  - Studies show tissues surrounding tumors have a role in cancer progression.

PMID- 15161877
TI  - Widespread statin use recommended for patients with type 2 diabetes.

PMID- 15161878
TI  - Rise in drug-resistant gonorrhea cases: spurs new treatment advice for gay,
      bisexual men.

PMID- 15161885
TI  - Iron stores as a risk factor for diabetes in women.

PMID- 15161886
TI  - Iron stores as a risk factor for diabetes in women.

PMID- 15161887
TI  - Reteplase in acute myocardial infarction.

PMID- 15161888
TI  - Differences between patients receiving peritoneal dialysis vs hemodialysis.

PMID- 15161889
TI  - Measuring the effects of therapy in Parkinson disease.

PMID- 15161890
TI  - Collagen content as a risk factor for urinary incontinence [corrected].

PMID- 15161891
TI  - The role of nurse practitioners in end-of-life care.

PMID- 15161892
TI  - Trial registration to prevent duplicate publication.

PMID- 15161893
TI  - Association of frequency and duration of aspirin use and hormone receptor status
      with breast cancer risk.
AB  - CONTEXT: Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
      has been associated with a decrease in the risk of several cancers, including
      breast cancer. NSAIDs inhibit cyclooxygenase activity and thereby reduce
      prostaglandin synthesis; prostaglandins stimulate aromatase gene expression and
      thereby stimulate estrogen biosynthesis. Given the importance of estrogen in the
      pathogenesis of breast cancer, the ability of aspirin and other NSAIDs to protect
      against breast cancer could vary according to hormone receptor status.
      OBJECTIVES: To determine the association between the frequency and duration of
      use of aspirin and other NSAIDs and breast cancer risk and to investigate whether
      any observed association is more pronounced for women with hormone receptor
      positive breast cancers. DESIGN, SETTING, AND PATIENTS: Population-based case
      control study of women with breast cancer, including in-person interviews
      conducted on Long Island, NY, during 1996-1997 (1442 cases and 1420 controls).
      MAIN OUTCOME MEASURE: Incident invasive and in situ breast cancer by aspirin and
      NSAID use and hormone receptor status. RESULTS: Ever use of aspirin or other
      NSAIDs at least once per week for 6 months or longer was reported in 301 cases
      (20.9%) and 345 controls (24.3%) (odds ratio [OR], 0.80; 95% confidence interval
      [CI], 0.66-0.97 for ever vs nonusers). The inverse association was most
      pronounced among frequent users (> or =7 tablets per week) (OR, 0.72; 95% CI,
      0.58-0.90). The results for ibuprofen, which was used by fewer women on a regular
      basis, were generally weaker (OR, 0.78; 95% CI, 0.55-1.10 for <3 times per week
      vs OR, 0.92; 95% CI, 0.70-1.22 for > or =3 times per week). Use of acetaminophen,
      an analgesic that does not inhibit prostaglandin synthesis, was not associated
      with a reduction in the incidence of breast cancer. The reduction in risk with
      aspirin use was seen among those with hormone receptor-positive tumors (OR, 0.74;
      95% CI, 0.60-0.93) but not for women with hormone receptor-negative tumors (OR,
      0.97; 95% CI, 0.67-1.40). CONCLUSION: These data add to the growing evidence that
      supports the regular use of aspirin and other NSAIDs (which may operate through
      inhibition of estrogen biosynthesis) as effective chemopreventive agents for
      breast cancer.

PMID- 15161894
TI  - Prognostic importance of comorbidity in a hospital-based cancer registry.
AB  - CONTEXT: Patients with cancer often have other medical ailments, referred to as
      comorbidity. Comorbidity may impact treatment decision-making, prognosis, and
      quality of care assessment. OBJECTIVE: To assess whether comorbidity information
      can provide important prognostic information in a hospital-based cancer registry.
      DESIGN, SETTING, AND PARTICIPANTS: An observational prospective cohort study
      using comorbidity data collected by trained hospital-based cancer registrars.
      Comorbidity was obtained through medical record review using the Adult
      Comorbidity Evaluation 27, a validated chart-based comorbidity instrument. A
      total of 17,712 patients receiving care between January 1, 1995, and January 31,
      2001, for the primary diagnosis of new cancer of the prostate, lung (nonsmall
      cell), breast, digestive system, gynecological, urinary system, or head and neck
      were included. MAIN OUTCOME MEASURE: Duration in months of overall survival.
      RESULTS: A total of 19,268 patients were included in the study; median duration
      of follow-up was 31 months. Of these patients, 1556 (8.0%) were excluded due to
      missing or unknown data. Severity of comorbidity strongly influenced survival in
      a dose-dependent fashion and the impact of comorbidity was independent of cancer
      stage. Compared with patients without comorbidity, the adjusted hazard ratio
      associated with mild comorbidity was 1.21 (95% confidence interval [CI], 1.13
      1.30), moderate comorbidity was 1.86 (95% CI, 1.73-2.00), and severe comorbidity
      was 2.56 (95% CI, 2.35-2.81). Adjusted Kaplan-Meier survival curves revealed that
      at any point in time the patients with more severe levels of comorbidity had
      worse survival (partial chi2(3) due to comorbidity, 523.54; P<.001). Model
      discrimination ranged from 0.71 for head and neck to 0.86 for prostate cancers.
      CONCLUSIONS: Comorbidity is an important independent prognostic factor for
      patients with cancer. The inclusion of comorbidity in hospital-based cancer
      registries will increase the value and use of observational research.

PMID- 15161895
TI  - Cognitive outcomes of preschool children with prenatal cocaine exposure.
AB  - CONTEXT: Because of methodological limitations, the results of the few
      prospective studies assessing long-term cognitive effects of prenatal cocaine
      exposure are inconsistent. OBJECTIVE: To assess effects of prenatal cocaine
      exposure and quality of caregiving environment on 4-year cognitive outcomes.
      DESIGN: Longitudinal, prospective, masked comparison cohort study from birth
      (September 1994-June 1996) to 4 years. SETTING: Research laboratory of a US urban
      county teaching hospital. PARTICIPANTS: A total of 415 consecutively enrolled
      infants identified from a high-risk population screened for drug use through
      clinical interview, urine, and meconium screens. Ninety-three percent retention
      for surviving participants at 4 years of age resulted in 376 children (190
      cocaine-exposed and 186 nonexposed). MAIN OUTCOME MEASURE: The Wechsler Preschool
      and Primary Scales of Intelligence-Revised. RESULTS: After control for
      covariates, prenatal cocaine exposure was not related to lower full-scale IQ
      (cocaine exposed [80.7] vs nonexposed [82.9]; P =.09) scores or summary verbal
      (cocaine exposed [79.9] vs nonexposed [81.9]; P =.11) or performance (cocaine
      exposed [85.5] vs nonexposed [87.5]; P =.18) IQ scores at age 4 years. However,
      prenatal cocaine exposure was related to small but significant deficits on
      several subscales (mean [SE]): visual-spatial skills (cocaine exposed [7.3
      (0.22)] vs nonexposed [8.2 (0.22)]; P =.01), general knowledge (cocaine exposed
      [6.1 (0.18)] vs nonexposed [6.7 (0.17)]; P =.04), and arithmetic skills (cocaine
      exposed [6.2 (0.20)] vs nonexposed [6.8 (0.20)]; P =.05). Prenatal cocaine
      exposure was also associated with a lower likelihood of achievement of IQ above
      normative means (odds ratio, 0.26 [95% confidence interval, 0.10-0.65]; P =.004).
      The quality of the caregiving environment was the strongest independent predictor
      of outcomes. Cocaine-exposed children placed in nonrelative foster or adoptive
      care lived in homes with more stimulating environments and had caregivers with
      better vocabulary scores, and they attained full-scale and performance IQ scores
      (83 and 87, respectively) similar to nonexposed children in biological maternal
      or relative care (full-scale IQ, 82; performance IQ, 88) and higher than cocaine
      exposed children in biological maternal or relative care (full-scale IQ, 79;
      performance IQ, 84). CONCLUSIONS: Prenatal cocaine exposure was not associated
      with lower full-scale, verbal, or performance IQ scores but was associated with
      an increased risk for specific cognitive impairments and lower likelihood of IQ
      above the normative mean at 4 years. A better home environment was associated
      with IQ scores for cocaine-exposed children that are similar to scores in
      nonexposed children.

PMID- 15161896
TI  - Empirical evidence for selective reporting of outcomes in randomized trials:
      comparison of protocols to published articles.
AB  - CONTEXT: Selective reporting of outcomes within published studies based on the
      nature or direction of their results has been widely suspected, but direct
      evidence of such bias is currently limited to case reports. OBJECTIVE: To study
      empirically the extent and nature of outcome reporting bias in a cohort of
      randomized trials. DESIGN: Cohort study using protocols and published reports of
      randomized trials approved by the Scientific-Ethical Committees for Copenhagen
      and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of
      reported and unreported trial outcomes were recorded from protocols, journal
      articles, and a survey of trialists. An outcome was considered incompletely
      reported if insufficient data were presented in the published articles for meta
      analysis. Odds ratios relating the completeness of outcome reporting to
      statistical significance were calculated for each trial and then pooled to
      provide an overall estimate of bias. Protocols and published articles were also
      compared to identify discrepancies in primary outcomes. MAIN OUTCOME MEASURES:
      Completeness of reporting of efficacy and harm outcomes and of statistically
      significant vs nonsignificant outcomes; consistency between primary outcomes
      defined in the most recent protocols and those defined in published articles.
      RESULTS: One hundred two trials with 122 published journal articles and 3736
      outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per
      trial were incompletely reported. Statistically significant outcomes had a higher
      odds of being fully reported compared with nonsignificant outcomes for both
      efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm
      (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles
      with protocols, 62% of trials had at least 1 primary outcome that was changed,
      introduced, or omitted. Eighty-six percent of survey responders (42/49) denied
      the existence of unreported outcomes despite clear evidence to the contrary.
      CONCLUSIONS: The reporting of trial outcomes is not only frequently incomplete
      but also biased and inconsistent with protocols. Published articles, as well as
      reviews that incorporate them, may therefore be unreliable and overestimate the
      benefits of an intervention. To ensure transparency, planned trials should be
      registered and protocols should be made publicly available prior to trial
      completion.

PMID- 15161897
TI  - Pitfalls of converting practice guidelines into quality measures: lessons learned
      from a VA performance measure.
AB  - The Department of Veterans Affairs (VA) manages the largest health care system in
      the United States, and the Institute of Medicine has recommended that many
      practices of VA quality measurement be applied to the US health care system as a
      whole. The VA measures quality of care at all of its sites by assessing adherence
      rates to performance measures, which generally are derived from evidence-based
      practice guidelines. Higher adherence rates are used as evidence of better
      quality of care. However, there are problems with converting practice guidelines,
      intended to offer guidance to clinicians, into performance measures that are
      meant to identify poor-quality care. We suggest a more balanced perspective on
      the use of performance measures to define quality by delineating conceptual
      problems with the conversion of practice guidelines into quality measures.
      Focusing on colorectal cancer screening, we use a case study at 1 VA facility to
      illustrate pitfalls that can cause adherence rates to guideline-based performance
      measures to be poor indicators of the quality of cancer screening. Pitfalls
      identified included (1) not properly considering illness severity of the sample
      population audited for adherence to screening, (2) not distinguishing screening
      from diagnostic procedures when setting achievable target screening rates, and
      (3) not accounting for patient preferences or clinician judgment when scoring
      performance measures. For many patients with severe comorbid illnesses or strong
      preferences against screening, the risks of colorectal cancer screening outweigh
      the benefits, and the decision to not screen may reflect good quality of care.
      Performance measures require more thoughtful specification and interpretation to
      avoid defining high testing rates as good quality of care regardless of who
      received the test, why it was performed, or whether the patient wanted it.

PMID- 15161898
TI  - Establishment of a pediatric oncology program and outcomes of childhood acute
      lymphoblastic leukemia in a resource-poor area.
AB  - CONTEXT: The cure rate for childhood acute lymphoblastic leukemia (ALL) differs
      markedly between developed and developing countries. OBJECTIVE: To assess the
      effect of a multidisciplinary team approach and protocol-based therapy on the
      event-free survival of children with ALL in an area with limited resources.
      DESIGN, POPULATION, AND SETTING: A retrospective cohort study at a pediatric
      hospital in the resource-poor city of Recife, Brazil. We reviewed medical records
      of the outcomes of 375 children with ALL diagnosed between 1980 and 2002. Eighty
      three children were diagnosed in the early period (1980-1989), in the absence of
      a dedicated pediatric oncology unit, protocol-based therapy, specially trained
      nurses, 24-hour on-site physician coverage, and ready access to intensive care.
      Seventy-eight children were treated (all according to protocol) during the middle
      period (July 1994 to March 1997). During the recent period (April 1997 to
      December 2002), 214 children were treated with protocol in a dedicated pediatric
      oncology unit staffed 24 hours by pediatric oncologists and oncology nurses.
      Improvements were implemented gradually during the middle period and were
      completed during the recent period. MAIN OUTCOME MEASURE: Event-free survival was
      estimated by the Kaplan-Meier method. Events included death from toxicity,
      disease progression or relapse, and abandonment of treatment. RESULTS: The 5-year
      event-free survival improved steadily: 32% (95% CI, 21%-43%) in the early period,
      47% (95% CI, 36%-58%) in the middle period, and 63% (95% CI, 55%-71%) in the
      recent period. The probability of cause-specific treatment failure in the early,
      middle, and late periods, respectively, within 1 year of diagnosis was 14% vs
      3.8% vs 3.3% for relapse; 6.0% vs 12% vs 9.8% for death from infection; 2.4% vs
      13% vs 4.2% for death from noninfectious toxicity; and 16% vs 1.3% vs 0.5% for
      abandonment of therapy. CONCLUSION: Treatment of childhood ALL in a dedicated
      pediatric oncology unit using a comprehensive multidisciplinary team approach,
      protocol-based therapy, and local support and funding is associated with improved
      outcomes in a resource-poor area.

PMID- 15161899
TI  - Palliative care for patients with heart failure.
AB  - Heart failure accounts for more hospitalizations among Medicare beneficiaries
      than any other condition. Its symptoms, including shortness of breath, fatigue,
      and edema, can be frightening and diminish quality of life. Although treatment
      advances have allowed patients to live longer with a better quality of life,
      heart failure remains a leading cause of death in the United States. Half of
      heart failure patients die within 5 years of diagnosis, and for many patients,
      death is sudden. Given the availability of effective treatments, the prevalence
      of distressing symptoms, and a persistent high risk of death that may occur
      suddenly, physicians must simultaneously treat the underlying condition while
      helping patients plan for future needs and complete advance directives. Using the
      case of Mr R, a 74-year-old man with heart failure, we illustrate ways that
      physicians can address these issues to improve the care of patients with heart
      failure, including symptom management and discussing advance directives,
      prognosis, and hospice care. By combining optimal medical management with
      palliative care, physicians can best care for heart failure patients and their
      families.

PMID- 15161900
TI  - Learning from SARS in Hong Kong and Toronto.

PMID- 15161901
TI  - Aspirin and breast cancer prevention: the estrogen connection.

PMID- 15161902
TI  - JAMA patient page. Preventing cancer.

PMID- 15161903
TI  - Glycoprotein hormone assembly in the endoplasmic reticulum: II. Multiple roles of
      a redox sensitive beta-subunit disulfide switch.
AB  - All three human glycoprotein hormone heterodimers are assembled in the
      endoplasmic reticulum by threading the glycosylated end of alpha-subunit loop two
      (alpha2) beneath a disulfide "latched" strand of the beta-subunit known as the
      "seatbelt." This remarkable event occurs efficiently even though the seatbelt
      effectively blocks the reverse process, thereby stabilizing each heterodimer.
      Studies described here show that assembly is facilitated by the formation,
      disruption, and reformation of a loop within the seatbelt that is stabilized by
      the most easily reduced disulfide in the free beta-subunit. We refer to this
      disulfide as the "tensor" because it shortens the seatbelt, thereby securing the
      heterodimer. Formation of the tensor disulfide appears to precede and facilitate
      seatbelt latching in most human choriogonadotropin beta-subunit molecules.
      Subsequent disruption of the tensor disulfide elongates the seatbelt, thereby
      increasing the space beneath the seatbelt and the beta-subunit core. This permits
      the formation of hydrogen bonds between backbone atoms of the beta-subunit
      cystine knot and the tensor loop with backbone atoms in loop alpha2, a process
      that causes the glycosylated end of loop alpha2 to be threaded between the
      seatbelt and the beta-subunit core. Contacts between the tensor loop and loop
      alpha2 promote reformation of the tensor disulfide, which explains why it is more
      stable in the heterodimer than in the uncombined beta-subunit. These findings
      unravel the puzzling nature of how a threading mechanism can be used in the
      endoplasmic reticulum to assemble glycoprotein hormones that have essential roles
      in vertebrate reproduction and thyroid function.

PMID- 15161904
TI  - Glycoprotein hormone assembly in the endoplasmic reticulum: III. The seatbelt and
      its latch site determine the assembly pathway.
AB  - Vertebrate glycoprotein hormone heterodimers are stabilized by a strand of their
      beta-subunits known as the "seatbelt" that is wrapped around loop 2 of their
      alpha-subunits (alpha2). The cysteine that terminates the seatbelt is "latched"
      by a disulfide to a cysteine in beta-subunit loop 1 (beta1) of all vertebrate
      hormones except some teleost follitropins (teFSH), wherein it is latched to a
      cysteine in the beta-subunit NH(2) terminus. As reported here, teFSH analogs of
      human choriogonadotropin (hCG) are assembled by a pathway in which the subunits
      dock before the seatbelt is latched; assembly is completed by wrapping the
      seatbelt around loop alpha2 and latching it to the NH(2) terminus. This differs
      from hCG assembly, which occurs by threading the glycosylated end of loop alpha2
      beneath the latched seatbelt through a hole in the beta-subunit. The seatbelt is
      the part of the beta-subunit that has the greatest influence on biological
      function. Changes in its sequence during the divergence of lutropins,
      follitropins, and thyrotropins and the speciation of teleost fish may have
      impeded heterodimer assembly by a threading mechanism, as observed when the hCG
      seatbelt was replaced with its salmon FSH counterpart. Whereas wrapping is less
      efficient than threading, it may have facilitated natural experimentation with
      the composition of the seatbelt during the co-evolution of glycoprotein hormones
      and their receptors. Migration of the seatbelt latch site to the NH(2)-terminal
      end of the beta-subunit would have facilitated teFSH assembly by a wraparound
      mechanism and may have contributed also to its ability to distinguish lutropin
      and follitropin receptors.

PMID- 15161905
TI  - A mitochondrial-vacuolar signaling pathway in yeast that affects iron and copper
      metabolism.
AB  - Mitochondria utilize iron, but the transporters that mediate mitochondrial iron
      uptake and efflux are largely unknown. Cells with a deletion in the vacuolar
      iron/manganese transporter Ccc1p are sensitive to high iron. Overexpression of
      MRS3 or MRS4 suppresses the high iron sensitivity of Deltaccc1 cells. MRS3 and
      MRS4 have recently been suggested to encode mitochondrial iron transporters. We
      demonstrate that deletion of MRS3 and MRS4 severely affects cellular and
      mitochondrial metal homeostasis, including a reduction in cytosolic and
      mitochondrial iron acquisition. We show that vacuolar iron transport is increased
      in Deltamrs3Deltamrs4 cells, resulting in decreased cytosolic iron and activation
      of the iron-sensing transcription factor Aft1p. Activation of Aft1p leads to
      increased expression of the high affinity iron transport system and increased
      iron uptake. Deletion of CCC1 in Deltamrs3Deltamrs4 cells restores cellular and
      mitochondrial iron homeostasis to near normal levels. Deltamrs3Deltamrs4 cells
      also show increased resistance to cobalt but decreased resistance to copper and
      cadmium. These phenotypes are also corrected by deletion of CCC1 in
      Deltamrs3Deltamrs4 cells. Decreased copper resistance in Deltamrs3Deltamrs4 cells
      results from activation of Aft1p by Ccc1p-mediated iron depletion, as deletion of
      CCC1 or AFT1 in Deltamrs3Deltamrs4 cells restores copper resistance. These
      results suggest that deletion of mitochondrial proteins can alter vacuolar metal
      homeostasis. The data also indicate that increased expression of the AFT1
      regulated gene(s) can disrupt copper homeostasis.

PMID- 15161906
TI  - Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone
      morphogenetic protein-induced osteoblast differentiation of mesenchymal stem
      cells.
AB  - Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and play an
      important role in development and in many cellular processes. We have found that
      BMP-2, BMP-6, and BMP-9 induce the most potent osteogenic differentiation of
      mesenchymal stem cells. Expression profiling analysis has revealed that the
      Inhibitors of DNA binding/differentiation (Id)-1, Id-2, and Id-3 are among the
      most significantly up-regulated genes upon BMP-2, BMP-6, or BMP-9 stimulation.
      Here, we sought to determine the functional role of these Id proteins in BMP
      induced osteoblast differentiation. We demonstrated that the expression of Id-1,
      Id-2, and Id-3 genes was significantly induced at the early stage of BMP-9
      stimulation and returned to basal levels at 3 days after stimulation. RNA
      interference-mediated knockdown of Id expression significantly diminished the BMP
      9-induced osteogenic differentiation of mesenchymal progenitor cells.
      Surprisingly, a constitutive overexpression of these Id genes also inhibited
      osteoblast differentiation initiated by BMP-9. Furthermore, we demonstrated that
      BMP-9-regulated Id expression is Smad4-dependent. Overexpression of the three Id
      genes was shown to promote cell proliferation that was coupled with an inhibition
      of osteogenic differentiation. Thus, our findings suggest that the Id helix-loop
      helix proteins may play an important role in promoting the proliferation of early
      osteoblast progenitor cells and that Id expression must be down-regulated during
      the terminal differentiation of committed osteoblasts, suggesting that a balanced
      regulation of Id expression may be critical to BMP-induced osteoblast lineage
      specific differentiation of mesenchymal stem cells.

PMID- 15161908
TI  - Thr-E11 regulates O2 affinity in Cerebratulus lacteus mini-hemoglobin.
AB  - The mini-hemoglobin from Cerebratulus lacteus (CerHb) belongs to a class of
      globins containing the polar Tyr-B10/Gln-E7 amino acid pair that normally causes
      low rates of O2 dissociation and ultra-high O2 affinity, which suggest O2 sensing
      or NO scavenging functions. CerHb, however, has high rates of O2 dissociation
      (kO2 = 200-600 s(-1)) and moderate O2 affinity (KO2) approximately 1 microm(-1))
      as a result of a third polar amino acid in its active site, Thr-E11. When Thr-E11
      is replaced by Val, kO2 decreases 1000-fold and KO2 increases 130-fold at pH 7.0,
      20 degrees C. The mutation also shifts the stretching frequencies of both heme
      bound and photodissociated CO, indicating marked changes of the electrostatic
      field at the active site. The crystal structure of Thr-E11 --> Val CerHbO2 at
      1.70 A resolution is almost identical to that of the wild-type protein (root mean
      square deviation of 0.12 A). The dramatic functional and spectral effects of the
      Thr-E11 --> Val mutation are due exclusively to changes in the hydrogen bonding
      network in the active site. Replacing Thr-E11 with Val "frees" the Tyr-B10
      hydroxyl group to rotate toward and donate a strong hydrogen bond to the heme
      bound ligand, causing a selective increase in O2 affinity, a decrease of the rate
      coefficient for O2 dissociation, a 40 cm(-1) decrease in nuCO of heme-bound CO,
      and an increase in ligand migration toward more remote intermediate sites.

PMID- 15161907
TI  - beta-D-Glucoside suppresses tumor necrosis factor-induced activation of nuclear
      transcription factor kappaB but potentiates apoptosis.
AB  - Mangiferin, a natural polyphenol is known to exhibit anti-inflammatory,
      antioxidant, and antiviral effects. However the molecular mechanism underlying
      these effects has not been well characterized. Because NF-kappaB plays an
      important role in these processes, it is possible that mangiferin modulates NF
      kappaB activation. Our results show that mangiferin blocks tumor necrosis factor
      (TNF)-induced NF-kappaB activation and NF-kappaB-dependent genes like ICAM1 and
      COX2. The effect was mediated through inhibition of IKK activation and subsequent
      blocking of phosphorylation and degradation of IkappaBalpha. In addition,
      mangiferin inhibits TNF-induced p65 phosphorylation as well as translocation to
      the nucleus and also inhibits NF-kappaB activation induced by other inflammatory
      agents like PMA, ceramide, and SA-LPS. Mangiferin, similar to the other known
      antioxidants, NAC and PDTC, inhibits TNF-induced reactive oxygen intermediate
      (ROI) generation. Since intracellular glutathione (GSH) levels are known to
      modulate NF-kappaB levels, we measured the levels of GSH. Mangiferin enhances
      glutathione level by almost 2-fold more than other anti-oxidants, and at the same
      time it decreases the levels of GSSG and increases the activity of catalase.
      Depletion of GSH by buthionine sulfoximine led to a significant reversal of
      mangiferin effect. Hence mangiferin with its ability to inhibit NF-kappaB and
      increase the intracellular GSH levels may prove to be a potent drug for anti
      inflammatory and antioxidant therapy. Mangiferin-mediated down-regulation of NF
      kappaB also potentiates chemotherapeutic agent-mediated cell death, suggesting a
      role in combination therapy for cancer.

PMID- 15161909
TI  - The Met receptor and alpha 6 beta 4 integrin can function independently to
      promote carcinoma invasion.
AB  - It has been proposed that a constitutive, physical association of the Met
      receptor and the alpha(6)beta(4) integrin exists on the surface of invasive
      carcinoma cells and that hepatocyte growth factor (HGF)-mediated invasion is
      dependent on alpha(6)beta(4) (Trusolino, L., Bertotti, A., and Comoglio, P. M.
      (2001) Cell 107, 643-654). The potential significance of these results prompted
      us to re-examine this hypothesis. Using three different carcinoma cell lines that
      express both Met and alpha(6)beta(4), we were unable to detect the constitutive
      association of these receptors by co-immunoprecipitation. Moreover, carcinoma
      cells that lacked expression of alpha(6)beta(4) exhibited Met-dependent invasion
      toward HGF, and increasing Met expression by viral infection of these cells
      enhanced invasion without inducing alpha(6)beta(4) expression. Although
      expression of alpha(6)beta(4) in such cells enhanced their invasion to HGF, it
      also enhanced their ability to invade toward other chemoattractants such as
      lysophosphatidic acid, and this latter invasion was not inhibited by a function
      blocking Met antibody. Finally, depletion of beta(4) by RNA interference in
      invasive carcinoma cells that express both receptors reduced the ability of these
      cells to invade toward HGF by approximately 25%, but it did not abrogate their
      invasion. These data argue that the invasive function of Met can be independent
      of alpha(6)beta(4) and that alpha(6)beta(4) has a generic influence on the
      invasion of carcinoma cells that is not specific to Met.

PMID- 15161910
TI  - Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells.
AB  - We previously reported that Nek11, a member of the NIMA (never-in-mitosis A)
      family of kinases, is activated in G(1)/S-arrested cells. We provide herein
      several lines of evidence for a novel interaction between Nek11 and Nek2A. Both
      Nek11 and Nek2A, but not Nek2B, were detected at nucleoli, and the Nek2A-specific
      C-terminal end (amino acids 399-445) was responsible for nucleolar localization.
      Endogenous Nek11 coimmunoprecipitated with endogenous Nek2A, and non-catalytic
      regions of each kinase were involved in the complex formation. Nek11L interacted
      with phosphorylated Nek2A but barely with the kinase-inactive Nek2A (K37R)
      mutant. In addition, both Nek2A autophosphorylation activity and the Nek11L-Nek2A
      complex formation increased in G(1)/S-arrested cells. These results indicate that
      autophosphorylation of Nek2A could stimulate its interaction with Nek11L at the
      nucleolus. Moreover, Nek2 directly phosphorylated Nek11 in the C-terminal non
      catalytic region and elevated Nek11 kinase activity. The non-catalytic region of
      Nek11 showed autoinhibitory activity through intramolecular interaction with its
      N-terminal catalytic domain. Nek2 dissociated this autoinhibitory interaction.
      Altogether, our studies demonstrate a unique mechanism of Nek11 activation by
      Nek2A in G(1)/S-arrested cells and suggest a novel possibility for nucleolar
      function of the NIMA family.

PMID- 15161911
TI  - B cell signaling is regulated by induced palmitoylation of CD81.
AB  - Signaling through the B cell antigen receptor (BCR) is amplified and prolonged by
      coligation of the BCR to the CD19/CD21/CD81 coreceptor complex. Coligation is
      induced during immune responses by the simultaneous binding of complement-tagged
      antigens to the complement receptor, CD21, and to the BCR. Enhanced signaling is
      due in part to the ability of the CD19/CD21/CD81 complex to stabilize the BCR in
      sphingolipid- and cholesterol-rich membrane microdomains termed lipid rafts. The
      tetraspanin CD81 is essential for the raft-stabilizing function of the
      coreceptor. Here we show that coligation of the BCR and the CD19/CD21/CD81
      complex leads to selective, rapid, and reversible palmitoylation of CD81 and that
      palmitoylation is necessary for the raft stabilizing function of the
      CD19/CD21/CD81 complex. Inducible palmitoylation may represent a novel mechanism
      by which tetraspanins function to facilitate lipid raft-dependent receptor
      signaling.

PMID- 15161912
TI  - Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1).
      Evidence that a tri-glutathione conjugate is required.
AB  - Inorganic arsenic is an established human carcinogen, but its metabolism is
      incompletely defined. The ATP binding cassette protein, multidrug resistance
      protein (MRP1/ABCC1), transports conjugated organic anions (e.g. leukotriene
      C(4)) and also co-transports certain unmodified xenobiotics (e.g. vincristine)
      with glutathione (GSH). MRP1 also confers resistance to arsenic in association
      with GSH; however, the mechanism and the species of arsenic transported are
      unknown. Using membrane vesicles prepared from the MRP1-overexpressing lung
      cancer cell line, H69AR, we found that MRP1 transports arsenite (As(III)) only in
      the presence of GSH but does not transport arsenate (As(V)) (with or without
      GSH). The non-reducing GSH analogs L-gamma-glutamyl-L-alpha-aminobutyryl glycine
      and S-methyl GSH did not support As(III) transport, indicating that the free
      thiol group of GSH is required. GSH-dependent transport of As(III) was 2-fold
      higher at pH 6.5-7 than at a more basic pH, consistent with the formation and
      transport of the acid-stable arsenic triglutathione (As(GS)(3)). Immunoblot
      analysis of H69AR vesicles revealed the unexpected membrane association of GSH S
      transferase P1-1 (GSTP1-1). Membrane vesicles from an MRP1-transfected HeLa cell
      line lacking membrane-associated GSTP1-1 did not transport As(III) even in the
      presence of GSH but did transport synthetic As(GS)(3). The addition of exogenous
      GSTP1-1 to HeLa-MRP1 vesicles resulted in GSH-dependent As(III) transport. The
      apparent K(m) of As(GS)(3) for MRP1 was 0.32 microM, suggesting a remarkably high
      relative affinity. As(GS)(3) transport by MRP1 was osmotically sensitive and was
      inhibited by several conjugated organic anions (MRP1 substrates) as well as the
      metalloid antimonite (K(i) 2.8 microM). As(GS)(3) transport experiments using
      MRP1 mutants with substrate specificities differing from wild-type MRP1 suggested
      a commonality in the substrate binding pockets of As(GS)(3) and leukotriene C(4).
      Finally, human MRP2 also transported As(GS)(3). In conclusion, MRP1 transports
      inorganic arsenic as a tri-GSH conjugate, and GSTP1-1 may have a synergistic role
      in this process.

PMID- 15161913
TI  - Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum.
AB  - Many proteins of the secretory pathway contain disulfide bonds that are essential
      for structure and function. In the endoplasmic reticulum (ER), Ero1 alpha and
      Ero1 beta oxidize protein disulfide isomerase (PDI), which in turn transfers
      oxidative equivalents to newly synthesized cargo proteins. However, oxidation
      must be limited, as some reduced PDI is necessary for disulfide isomerization and
      ER-associated degradation. Here we show that in semipermeable cells, PDI is more
      oxidized, disulfide bonds are formed faster, and high molecular mass covalent
      protein aggregates accumulate in the absence of cytosol. Addition of reduced
      glutathione (GSH) reduces PDI and restores normal disulfide formation rates. A
      higher GSH concentration is needed to balance oxidative folding in semipermeable
      cells overexpressing Ero1 alpha, indicating that cytosolic GSH and lumenal Ero1
      alpha play antagonistic roles in controlling the ER redox. Moreover, the
      overexpression of Ero1 alpha significantly increases the GSH content in HeLa
      cells. Our data demonstrate tight connections between ER and cytosol to guarantee
      redox exchange across compartments: a reducing cytosol is important to ensure
      disulfide isomerization in secretory proteins.

PMID- 15161914
TI  - Nonsense mutations in close proximity to the initiation codon fail to trigger
      full nonsense-mediated mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades
      mRNAs containing premature translation termination codons. In mammalian cells, a
      termination codon is ordinarily recognized as "premature" if it is located
      greater than 50-54 nucleotides 5' to the final exon-exon junction. We have
      described a set of naturally occurring human beta-globin gene mutations that
      apparently contradict this rule. The corresponding beta-thalassemia genes contain
      nonsense mutations within exon 1, and yet their encoded mRNAs accumulate to
      levels approaching wild-type beta-globin (beta(WT)) mRNA. In the present report
      we demonstrate that the stabilities of these mRNAs with nonsense mutations in
      exon 1 are intermediate between beta(WT) mRNA and beta-globin mRNA carrying a
      prototype NMD-sensitive mutation in exon 2 (codon 39 nonsense; beta 39).
      Functional analyses of these mRNAs with 5'-proximal nonsense mutations
      demonstrate that their relative resistance to NMD does not reflect abnormal RNA
      splicing or translation re-initiation and is independent of promoter identity and
      erythroid specificity. Instead, the proximity of the nonsense codon to the
      translation initiation AUG constitutes a major determinant of NMD. Positioning a
      termination mutation at the 5' terminus of the coding region blunts mRNA
      destabilization, and this effect is dominant to the "50-54 nt boundary rule."
      These observations impact on current models of NMD.

PMID- 15161915
TI  - Inhibition by copper(II) binding of hepatocyte growth factor (HGF) interaction
      with its receptor Met and blockade of HGF/Met function.
AB  - Overexpression of hepatocyte growth factor (HGF) and its receptor Met often
      occurs in carcinoma cells, leading to establishment of an HGF/Met autocrine loop.
      Therefore, disruption of the HGF/Met autocrine loop may lead to down-regulation
      of tumorigenesis. To study the HGF/Met interaction, we have developed a cell-free
      system to detect HGF binding to a Met fusion protein, Met-IgG, using a modified
      enzyme-linked immunosorbent assay methodology. Since we previously showed that
      HGF can be purified by copper(II) affinity chromatography, we further explored
      the effect of copper(II) on the HGF/Met interaction. The divalent metal cations
      copper(II) and zinc(II) significantly inhibited HGF binding to immobilized Met
      IgG with IC(50) values of 230-270 microM, respectively, whereas manganese(II) and
      magnesium(II) were less inhibitory with 20-60-fold higher IC(50) values.
      Incubation of 1 mM copper(II) with HGF resulted in nondenaturing and denaturing
      gel-mobility shifts, indicating that copper(II) binds directly to HGF. This
      interaction occurs at the N terminus of HGF, as incubation of 1 mM copper(II)
      with both HGF and the HGF derivative NK1 yielded similar results on SDS-PAGE. HGF
      induced activation of Met and cell scattering were inhibited upon addition of HGF
      in the presence of 1 mM and 500 microM copper(II), respectively. Chemical
      protonation with diethyl pyrocarbonate of HGF histidine residues impeded the
      ability of 500 microM copper(II) to inhibit the binding of HGF to immobilized Met
      IgG. Based on the NK1 domain structure, we propose that copper(II) may interact
      with HGF via the histidine residues in either N-terminal or kringle domains. The
      inhibition of HGF/Met interaction and subsequent downstream cellular functions
      may be through direct interference by copper(II), such as a change in charge or
      an induced local conformational change. This putative copper(II) binding domain
      may be the basis for developing potential inhibitors of HGF/Met binding and
      downstream functions and could lead to novel strategies for anti-cancer
      treatment.

PMID- 15161916
TI  - Mechanism of tyrosine phosphorylation and activation of phospholipase C-gamma 1.
      Tyrosine 783 phosphorylation is not sufficient for lipase activation.
AB  - Phospholipase C-gamma 1 (PLC-gamma 1) is phosphorylated on three tyrosine
      residues: Tyr-771, Tyr-783, and Tyr-1253. With the use of antibodies specific for
      each of these phosphorylation sites, we have now determined the kinetics and
      magnitude of phosphorylation at each site. Phosphorylation of Tyr-783, which is
      essential for lipase activation, was observed in all stimulated cell types
      examined. The extent of phosphorylation of Tyr-1253 was approximately 50 to 70%
      of that of Tyr-783 in cells stimulated with platelet-derived growth factor (PDGF)
      or epidermal growth factor (EGF), but Tyr-1253 phosphorylation was not detected
      in B or T cell lines stimulated through B- and T-cell antigen receptors,
      respectively. Tyr-771 was phosphorylated only at a low level in all cells
      studied. In cells stimulated with PDGF, phosphorylation and dephosphorylation of
      Tyr-783 and of Tyr-1253 occurred with similar kinetics; the receptor kinase
      appeared to phosphorylate both sites, albeit with Tyr-783 favored over Tyr-1253,
      before the bound PLC-gamma 1 was released, and phosphorylation at the two sites
      occurred independently. PDGF and EGF induced similar levels of phosphorylation of
      Tyr-783 and of Tyr-1253 in a cell line that expressed receptors for both growth
      factors. However, only PDGF, not EGF, elicited substantial PLC activity,
      suggesting that Tyr-783 phosphorylation was not sufficient for enzyme activation.
      Finally, concurrent production of phosphatidylinositol 3,4,5-trisphosphate was
      found to contribute to the activation of phosphorylated PLC-gamma 1.

PMID- 15161917
TI  - Consequences of cysteine mutations in calcium-binding epidermal growth factor
      modules of fibrillin-1.
AB  - Mutations in fibrillin-1 lead to Marfan syndrome and some related genetic
      disorders. Many of the more than 600 mutations currently known in fibrillin-1
      eliminate or introduce cysteine residues in epidermal growth factor-like modules.
      Here we report structural and functional consequences of three selected cysteine
      mutations (R627C, C750G, and C926R) in fibrillin-1. The mutations have been
      analyzed by means of recombinant polypeptides produced in mammalian expression
      systems. The mRNA levels for the mutation constructs were similar to wild-type
      levels. All three mutated polypeptides were secreted by embryonic kidney cells
      (293) into the culture medium. Purification was readily feasible for mutants
      R627C and C750G, but not for C926R, which restricted the availability of this
      mutant polypeptide to selected analyses. The overall folds of the mutant
      polypeptides were indistinguishable from the wild-type as judged by the
      ultrastructural shape, CD analysis, and reactivity with a specific antibody
      sensitive for intact disulfide bonds. Subtle structural changes caused by R627C
      and C750G, however, were monitored by proteolysis and heat denaturation
      experiments. These changes occurred in the vicinity of the mutations either as
      short range effects (R627C) or both short and long range effects (C750G).
      Enhanced proteolytic susceptibility was observed for R627C and C750G to a variety
      of proteases. These results expand and further strengthen the concept that
      proteolytic degradation of mutated fibrillin-1 might be an important potential
      mechanism in the pathogenesis of Marfan syndrome and other disorders caused by
      mutations in fibrillin-1.

PMID- 15161918
TI  - Glycoprotein hormone assembly in the endoplasmic reticulum: I. The glycosylated
      end of human alpha-subunit loop 2 is threaded through a beta-subunit hole.
AB  - Glycoprotein hormone heterodimers are stabilized by their unusual structures in
      which a glycosylated loop of the alpha-subunit straddles a hole in the beta
      subunit. This hole is formed when a cysteine at the end of a beta-subunit strand
      known as the "seatbelt" becomes "latched" by a disulfide to a cysteine in the
      beta-subunit core. The heterodimer is stabilized in part by the difficulty of
      threading the glycosylated end of the alpha-subunit loop 2 through this hole, a
      phenomenon required for subunit dissociation. Subunit combination in vitro, which
      occurs by the reverse process, can be accelerated by removing the alpha-subunit
      oligosaccharide. In cells, heterodimer assembly was thought to occur primarily by
      a mechanism in which the seatbelt is wrapped around the alpha-subunit after the
      subunits dock. Here we show that this "wraparound" process can be used to
      assemble disulfide cross-linked human choriogonadotropin analogs that contain an
      additional alpha-subunit cysteine, but only if the normal beta-subunit latch site
      has been removed. Normally, the seatbelt is latched before the subunits dock and
      assembly is completed when the glycosylated end of alpha-subunit loop 2 is
      threaded beneath the seatbelt. The unexpected finding that most assembly of human
      choriogonadotropin, human follitropin, and human thyrotropin heterodimers occurs
      in this fashion, indicates that threading may be an important phenomenon during
      protein folding and macromolecule assembly in the endoplasmic reticulum. We
      suggest that the unusual structures of the glycoprotein hormones makes them
      useful for identifying factors that influence this process in living cells.

PMID- 15161919
TI  - Photocross-linking of the RNA polymerase I preinitiation and immediate
      postinitiation complexes: implications for promoter recruitment.
AB  - The architecture of eukaryotic rRNA transcription complexes was analyzed,
      revealing facts significant to the RNA polymerase (pol) I initiation process.
      Functional initiation and elongation complexes were mapped by site-specific
      photocross-linking to template DNA. Polymerase I is recruited to the promoter via
      protein-protein interactions with DNA-bound transcription initiation factor-IB.
      The latter's TATA-binding protein (TBP) and TAFs photocross-link to the promoter
      from -78 to +10 relative to the tis (+1). Although TBP does not bind DNA using
      its TATA-binding saddle, it does photocross-link to a 22-bp sequence that does
      not resemble a TATA box. Only TAF(I)96 (the mammalian TAF(I) 68, yeast Rrn7p
      homolog) overlaps significantly with the DNA interaction cleft of pol I based on
      modeling to the pol II crystal structure. None of the pol I-specific subunits
      that are localized on the lips of the cleft (A49 and A34.5) or the pol I-specific
      stalk (A43 and A14) cross-link to DNA. Pol I does not extend significantly
      upstream of the promoter-proximal border of the factor complex (-11 to -14), and
      similarly in the promoter proximal elongation complex, the enzyme does not
      contact DNA upstream of its normal exit from the cleft.

PMID- 15161920
TI  - Embryonic fibroblasts with a gene trap mutation in Ext1 produce short heparan
      sulfate chains.
AB  - Mutational defects in either EXT1 or EXT2 genes cause multiple exostoses, an
      autosomal hereditary human disorder. The EXT1 and EXT2 genes encode
      glycosyltransferases that play an essential role in heparan sulfate chain
      elongation. In this study, we have analyzed heparan sulfate synthesized by
      primary fibroblast cell cultures established from mice with a gene trap mutation
      in Ext1. The gene trap mutation results in embryonic lethality, and homozygous
      mice die around embryonic day 14. Metabolic labeling and immunohistochemistry
      revealed that Ext1 mutant fibroblasts still produced small amounts of heparan
      sulfate. The domain structure of the mutant heparan sulfate was conserved, and
      the disaccharide composition was similar to that of wild type heparan sulfate.
      However, a dramatic difference was seen in the polysaccharide chain length. The
      average molecular sizes of the heparan sulfate chains from wild type and Ext1
      mutant embryonic fibroblasts were estimated to be around 70 and 20 kDa,
      respectively. These data suggest that not only the sulfation pattern but also the
      length of the heparan sulfate chains is a critical determinant of normal mouse
      development.

PMID- 15161921
TI  - ppGpp-dependent stationary phase induction of genes on Salmonella pathogenicity
      island 1.
AB  - We have examined expression of the genes on Salmonella pathogenicity island 1
      (SPI1) during growth under the physiologically well defined standard growth
      condition of Luria-Bertani medium with aeration. We found that the central
      regulator hilA and the genes under its control are expressed at the onset of
      stationary phase. Interestingly, the two-component regulatory genes hilC/hilD,
      sirA/barA, and ompR, which are known to modulate expression from the hilA
      promoter (hilAp) under so-called "inducing conditions" (Luria-Bertani medium
      containing 0.3 m NaCl without aeration), acted under standard conditions at the
      stationary phase induction level. The induction of hilAp depended not on RpoS,
      the stationary phase sigma factor, but on the stringent signal molecule ppGpp. In
      the ppGpp null mutant background, hilAp showed absolutely no activity. The
      stationary phase induction of hilAp required spoT but not relA. Consistent with
      this requirement, hilAp was also induced by carbon source deprivation, which is
      known to transiently elevate ppGpp mediated by spoT function. The observation
      that amino acid starvation elicited by the addition of serine hydroxamate did not
      induce hilAp in a RelA(+) SpoT(+) strain suggested that, in addition to ppGpp,
      some other alteration accompanying entry into the stationary phase might be
      necessary for induction. It is speculated that during the course of infection
      Salmonella encounters various stressful environments that are sensed and
      translated to the intracellular signal, ppGpp, which allows expression of
      Salmonella virulence genes, including SPI1 genes.

PMID- 15161923
TI  - ADAMTS4 (aggrecanase-1) interaction with the C-terminal domain of fibronectin
      inhibits proteolysis of aggrecan.
AB  - ADAMTS4 (aggrecanase-1), a secreted enzyme belonging to the ADAMTS (a disintegrin
      and metalloproteinase with thrombospondin motifs) gene family, is considered to
      play a key role in the degradation of cartilage proteoglycan (aggrecan) in
      osteoarthritis and rheumatoid arthritis. To clone molecules that bind to ADAMTS4,
      we screened a human chondrocyte cDNA library by the yeast two-hybrid system using
      the ADAMTS4 spacer domain as bait and obtained cDNA clones derived from
      fibronectin. Interaction between ADAMTS4 and fibronectin was demonstrated by
      chemical cross-linking. A yeast two-hybrid assay and solid-phase binding assay
      using wild-type fibronectin and ADAMTS4 and their mutants demonstrated that the C
      terminal domain of fibronectin is capable of binding to the C-terminal spacer
      domain of ADAMTS4. Wild-type ADAMTS4 was co-localized with fibronectin as
      determined by confocal microscopy on the cell surface of stable 293T
      transfectants expressing ADAMTS4, although ADAMTS4 deletion mutants, including
      Delta Sp (Delta Arg(693)-Lys(837), lacking the spacer domain), showed negligible
      localization. The aggrecanase activity of wild-type ADAMTS4 was dose-dependently
      inhibited by fibronectin (IC(50) = 110 nm), whereas no inhibition was observed
      with Delta Sp. The C-terminal 40-kDa fibronectin fragment also inhibited the
      activity of wild-type ADAMTS4 (IC(50) = 170 nm). These data demonstrate for the
      first time that the aggrecanase activity of ADAMTS4 is inhibited by fibronectin
      through interaction with their C-terminal domains and suggest that this
      extracellular regulation mechanism of ADAMTS4 activity may be important for the
      degradation of aggrecan in arthritic cartilage.

PMID- 15161922
TI  - Temporal regulation of VEID-7-amino-4-trifluoromethylcoumarin cleavage activity
      and caspase-6 correlates with organelle loss during lens development.
AB  - Lens fiber cell differentiation involves extensive reconstruction of the cell's
      architecture, including the degradation and elimination of all membrane-bound
      organelles via a process that has been likened to apoptosis. Using caspase
      reporter assays under conditions in which nonspecific cleavage of the reporter
      peptides by the proteasome has been inhibited, we investigated whether any
      specific caspase activities are temporally correlated with this process of
      organelle loss. Extracts from neonatal mouse lenses contained strong VEID-7-amino
      4-trifluoromethylcoumarin (AFC) and minor IETD-AFC and LEVD-AFC cleavage
      activities, but no DEVD-AFC cleavage activity. Further testing suggested that the
      VEID-AFC and IETD-AFC cleavage activities were likely due to the same enzyme. In
      lens extracts from rat embryos, VEID-AFC cleavage activity increased during the
      period when organelles are eliminated, between embryonic days 15.5 and 18.5,
      whereas procaspase-6 protein levels decreased, suggesting that this enzyme is
      responsible for VEID-AFC cleavage. By contrast, in extracts from alpha AE7
      transgenic mouse lenses in which apoptosis was induced, strong DEVD-AFC cleavage
      activity and activated caspase-3 protein were detected. Thus, within the same
      tissue, different caspase activities can predominate depending on the context,
      normal differentiation versus apoptosis. These results highlight the difference
      between normal fiber cell differentiation and apoptosis and the capacity of the
      lens to differentially regulate these two processes.

PMID- 15161924
TI  - A novel function for fatty acid translocase (FAT)/CD36: involvement in long chain
      fatty acid transfer into the mitochondria.
AB  - Fatty acid translocase (FAT)/CD36 is a long chain fatty acid transporter present
      at the plasma membrane, as well as in intracellular pools of skeletal muscle. In
      this study, we assessed the unexpected presence of FAT/CD36 in both
      subsarcolemmal and intermyofibril fractions of highly purified mitochondria.
      Functional assessments demonstrated that the mitochondria could bind (14)C
      labeled palmitate, but could only oxidize it in the presence of carnitine.
      However, the addition of sulfo-N-succinimidyl oleate, a known inhibitor of
      FAT/CD36, resulted in an 87 and 85% reduction of palmitate oxidation in
      subsarcolemmal and intermyofibril fractions, respectively. Further studies
      revealed that maximal carnitine palmitoyltransferase I (CPTI) activity in vitro
      was inhibited by succinimidyl oleate (42 and 48% reduction). Interestingly, CPTI
      immunoprecipitated with FAT/CD36, indicating a physical pairing. Tissue
      differences in mitochondrial FAT/CD36 protein follow the same pattern as the
      capacity for fatty acid oxidation (heart >> red muscle > white muscle).
      Additionally, chronic stimulation of hindlimb muscles (7 days) increased FAT/CD36
      expression and also resulted in a concomitant increase in mitochondrial FAT/CD36
      content (46 and 47% increase). Interestingly, with acute electrical stimulation
      of hindlimb muscles (30 min), FAT/CD36 expression was not altered, but there was
      an increase in the mitochondrial content of FAT/CD36 compared with the non
      stimulated control limb (35 and 37% increase). Together, these data suggest a
      role for FAT/CD36 in mitochondrial long chain fatty acid uptake and demonstrate
      system flexibility to match FAT/CD36 mitochondrial content with an increased
      capacity for fatty acid oxidation, possibly involving translocation of FAT/CD36
      to the mitochondria.

PMID- 15161926
TI  - Modulation of FcgammaRI (CD64) ligand binding by blocking peptides of periplakin.
AB  - FcgammaRI requires both the intracellular domain of the alpha-chain and
      associated leukocyte Fc receptor (FcR) gamma-chains for its biological function.
      We recently found the C terminus of periplakin to selectively interact with the
      cytoplasmic domain of the FcgammaRI alpha-chain. It thereby enhances the capacity
      of FcgammaRI to bind, internalize, and present antigens on MHC class II. Here, we
      characterized the domains involved in FcgammaRI-periplakin interaction using
      truncated and alanine-substituted FcgammaRI mutants and randomly mutagenized
      periplakin. This allowed us to design TAT peptides that selectively interfered
      with endogenous FcgammaRI-periplakin interactions. The addition of these peptides
      to FcgammaRI-expressing cells modulated FcgammaRI ligand binding, as assessed by
      erythrocyte-antibody-rosetting. These data support a dominant-negative role of C
      terminal periplakin for FcgammaRI biological activity and implicate periplakin as
      a novel regulator of FcgammaRI in immune cells.

PMID- 15161925
TI  - Identification of a nuclear export signal and protein interaction domains in
      deformed epidermal autoregulatory factor-1 (DEAF-1).
AB  - Deformed epidermal autoregulatory factor-1 (DEAF-1) is a DNA-binding protein
      required for embryonic development and linked to clinical depression and suicidal
      behavior in humans. Although primarily nuclear, cytoplasmic localization of DEAF
      1 has been observed, and this suggests the presence of a nuclear export signal
      (NES). Using a series of fluorescent fusion proteins, an NES with a novel spacing
      of leucines (LXLX(6)LLX(5)LX(2)L) was identified near the COOH-terminal MYND
      domain at amino acids 454-476. The NES was leptomycin B-sensitive and mutation of
      the leucine residues decreased or eliminated nuclear export activity. In vitro
      pull downs and an in vivo fluorescent protein interaction assay identified a DEAF
      1/DEAF-1 protein interaction domain within the NES region. DNA binding had been
      previously mapped to a positively charged surface patch in the novel DNA binding
      fold called the "SAND" domain. A second protein-protein interaction domain was
      identified at amino acids 243-306 that contains the DNA-binding SAND domain and
      also an adjacent zinc binding motif and a monopartite nuclear localization signal
      (NLS). Deletion of these adjacent sequences or mutation of the conserved
      cysteines or histidine in the zinc binding motif not only inhibits protein
      interaction but also eliminates DNA binding, demonstrating that DEAF-1 protein
      protein interaction is required for DNA recognition. The identification of an NES
      and NLS provides a basis for the control of DEAF-1 subcellular localization and
      function, whereas the requirement of protein-protein interaction by the SAND
      domain appears to be unique among this class of transcription factors.

PMID- 15161927
TI  - Null mutation of peroxisome proliferator-activated receptor-interacting protein
      in mammary glands causes defective mammopoiesis.
AB  - To investigate the role of nuclear receptor coactivator peroxisome proliferator
      activated receptor-interacting protein (PRIP) in mammary gland development, we
      generated a conditional null mutation of PRIP in mammary glands. In PRIP
      deficient mammary glands, the elongation of ducts during puberty was not
      affected, but the numbers of ductal branches were decreased, a condition that
      persisted long after puberty, indicating that the potential of ductal branching
      was impaired. During pregnancy, PRIP-deficient mammary glands exhibited decreased
      alveolar density. The lactating PRIP-deficient glands contained scant
      lobuloalveoli with many adipocytes, whereas the wild type glands were composed of
      virtually no adipocytes but mostly lobuloalveoli. As a result, PRIP mammary
      deficient glands could not produce enough milk to nurse all the pups during
      lactation. The ductal branching of mammary glands in response to estrogen
      treatment was attenuated in PRIP mutant glands. Whereas the proliferation index
      was similar between wild type and PRIP-deficient glands, increased apoptosis was
      observed in PRIP-deficient glands. PRIP-deficient glands expressed increased
      amphiregulin, transforming growth factor-alpha, and betacellulin mRNA as compared
      with wild type glands. The differentiated function of PRIP-deficient mammary
      epithelial cells was largely intact, as evidenced by the expression of abundant
      beta-casein, whey acidic protein (WAP), and WDNM1 mRNA. We conclude that PRIP is
      important for normal mammary gland development.

PMID- 15161928
TI  - Mutation of tyrosine in the conserved NPXXY sequence leads to constitutive
      phosphorylation and internalization, but not signaling, of the human B2
      bradykinin receptor.
AB  - Although the G protein-coupled receptors (GPCRs) share a similar seven
      transmembrane domain structure, only a limited number of amino acid residues is
      conserved in their protein sequences. One of the most highly conserved sequences
      is the NPXXY motif located at the cytosolic end of the transmembrane region-7 of
      many GPCRs, particularly of those belonging to the family of the rhodopsin/beta
      adrenergic-like receptors. Exchange of Tyr(305) in the corresponding NPLVY
      sequence of the bradykinin B(2) receptor (B(2)R) for Ala resulted in a mutant,
      termed Y305A, that internalized [(3)H]bradykinin (BK) almost as rapidly as the
      wild-type (wt) B(2)R. However, receptor sequestration of the mutant after
      stimulation with BK was clearly reduced relative to the wt B(2)R. Confocal
      fluorescence microscopy revealed that, in contrast to the B(2)R-enhanced green
      fluorescent protein chimera, the Y305A-enhanced green fluorescent protein chimera
      was predominantly located intracellularly even in the absence of BK. Two
      dimensional phosphopeptide analysis showed that the mutant Y305A constitutively
      exhibited a phosphorylation pattern similar to that of the BK-stimulated wt
      B(2)R. Ligand-independent Y305A internalization was demonstrated by the uptake of
      rhodamine-labeled antibodies directed to a tag sequence at the N terminus of the
      mutant receptor. Co-immunoprecipitation revealed that Y305A is precoupled to
      G(q/11) without activating the G protein because the basal accumulation rate of
      inositol phosphate was unchanged as compared with wt B(2)R. We conclude,
      therefore, that the Y305A mutation of B(2)R induces a receptor conformation which
      is prone to ligand-independent phosphorylation and internalization. The mutated
      receptor binds to, but does not activate, its cognate heterotrimeric G protein
      G(q/11), thereby limiting the extent of ligand-independent receptor
      internalization.

PMID- 15161929
TI  - Organ hypertrophic signaling within caveolae membrane subdomains triggered by
      ouabain and antagonized by PST 2238.
AB  - In addition to inhibition of the Na-K ATPase, ouabain activates a signal
      transduction function, triggering growth and proliferation of cultured cells even
      at nanomolar concentrations. An isomer of ouabain (EO) circulates in mammalians
      at subnanomolar concentrations, and increased levels are associated with cardiac
      hypertrophy and hypertension. We present here a study of cardiac and renal
      hypertrophy induced by ouabain infused into rats for prolonged periods and relate
      this effect to the recently described ouabain-induced activation of the Src-EGFr
      ERK signaling pathway. Ouabain infusion into rats (15 microg/kg/day for 18 weeks)
      doubled plasma ouabain levels from 0.3 to 0.7 nm and increased blood pressure by
      20 mm Hg (p < 0.001), cardiac left ventricle (+11%, p < 0.05), and kidney weight
      (+9%, p < 0.01). These effects in vivo are associated with a significant
      enrichment of alpha1, beta1, gammaa Na-K ATPase subunits together with Src and
      EGFr in isolated renal caveolae membranes and activation of ERK1/2. In caveolae,
      direct Na-K ATPase/Src interactions can be demonstrated by co
      immunoprecipitation. The interaction is amplified by ouabain, at a high affinity
      binding site, detectable in caveolae but not in total rat renal membranes. The
      high affinity site for ouabain is associated with Src-dependent tyrosine
      phosphorylation of rat alpha1 Na-K ATPase. The antihypertensive compound, PST
      2238, antagonized all ouabain-induced effects at 10 microg/kg/day in vivo or 10(
      10)-10(-8) m in vitro. These findings provide a molecular mechanism for the in
      vivo pro-hypertrophic and hypertensinogenic activity of ouabain, or by analogy
      those of EO in humans. They also explain the pharmacological basis for PST 2238
      treatment.

PMID- 15161930
TI  - Structural basis for the deactivation of the estrogen-related receptor gamma by
      diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity.
AB  - The estrogen-related receptor (ERR) gamma behaves as a constitutive activator of
      transcription. Although no natural ligand is known, ERRgamma is deactivated by
      the estrogen receptor (ER) agonist diethylstilbestrol and the selective ER
      modulator 4-hydroxytamoxifen but does not significantly respond to estradiol or
      raloxifene. Here we report the crystal structures of the ERRgamma ligand binding
      domain (LBD) complexed with diethylstilbestrol or 4-hydroxytamoxifen. Antagonist
      binding to ERRgamma results in a rotation of the side chain of Phe-435 that
      partially fills the cavity of the apoLBD. The new rotamer of Phe-435 displaces
      the "activation helix" (helix 12) from the agonist position observed in the
      absence of ligand. In contrast to the complexes of the ERalpha LBD with 4
      hydroxytamoxifen or raloxifene, helix 12 of antagonist-bound ERRgamma does not
      occupy the coactivator groove but appears to be completely dissociated from the
      LBD body. Comparison of the ligand-bound LBDs of ERRgamma and ERalpha reveals
      small but significant differences in the architecture of the ligand binding
      pockets that result in a slightly shifted binding position of diethylstilbestrol
      and a small rotation of 4-hydroxytamoxifen in the cavity of ERRgamma relative to
      ERalpha. Our results provide detailed molecular insight into the conformational
      changes occurring upon binding of synthetic antagonists to the constitutive
      orphan receptor ERRgamma and reveal structural differences with ERs that explain
      why ERRgamma does not bind estradiol or raloxifene and will help to design new
      selective antagonists.

PMID- 15161932
TI  - Leucyl-tRNA synthetase from the hyperthermophilic bacterium Aquifex aeolicus
      recognizes minihelices.
AB  - Aminoacylation of the minihelix mimicking the amino acid acceptor arm of tRNA has
      been demonstrated in more than 10 aminoacyl-tRNA synthetase systems. Although
      Escherichia coli or Homo sapiens cytoplasmic leucyl-tRNA synthetase (LeuRS) is
      unable to charge the cognate minihelix or microhelix, we show here that
      minihelix(Leu) is efficiently charged by Aquifex aeolicus synthetase, the only
      known heterodimeric LeuRS (alpha beta-LeuRS). Aminoacylation of minihelices is
      strongly dependent on the presence of the A73 identity nucleotide and greatly
      stimulated by destabilization of the first base pair as reported for the E. coli
      isoleucyl-tRNA synthetase and methionyl-tRNA synthetase systems. In the E. coli
      LeuRS system, the anticodon of tRNA(Leu) is not important for recognition by the
      synthetase. However, the addition of RNA helices that mimic the anticodon domain
      stimulates minihelix(Leu) charging by alpha beta-LeuRS, indicating possible
      domain-domain communication within alpha beta-LeuRS. The leucine-specific domain
      of alpha beta-LeuRS is responsible for minihelix recognition. To ensure accurate
      translation of the genetic code, LeuRS functions to hydrolyze misactivated amino
      acids (pretransfer editing) and misaminoacylated tRNA (posttransfer editing). In
      contrast to tRNA(Leu), minihelix(Leu) is unable to induce posttransfer editing
      even upon the addition of the anticodon domain of tRNA. Therefore, the context of
      tRNA is crucial for the editing of mischarged products. However, the
      minihelix(Leu) cannot be misaminoacylated, perhaps because of the tRNA
      independent pretransfer editing activity of alpha beta-LeuRS.

PMID- 15161931
TI  - DLP, a novel Dim1 family protein implicated in pre-mRNA splicing and cell cycle
      progression.
AB  - In eukaryotes, primary transcripts undergo a splicing process that removes
      intronic sequences by a macromolecular enzyme known as the spliceosome. Both
      genetic and biochemical studies have revealed that essential components of the
      spliceosome include five small RNAs, U1, U2, U4, U5, and U6, and as many as 300
      distinct proteins. Here we report the molecular cloning and functional analysis
      of a novel cDNA encoding for a protein of 149 amino acids. This protein has 38%
      amino acid sequence identity with and is evolutionally related to yeast Dim1
      protein. Hence we named this protein DLP for Dim1-like protein. We showed that
      DLP is required for S/G(2) transition. We also demonstrated that DLP functions in
      cell nucleus and interacts with the U5-102-kDa protein subunit of the
      spliceosome, and blocking DLP protein activity led to an insufficient pre-mRNA
      splicing, suggesting that DLP is yet another protein component involved in pre
      mRNA splicing. Collectively, our experiments indicated that DLP is implicated in
      not only cell cycle progression but also in a more specific molecular process
      such as pre-mRNA splicing.

PMID- 15161933
TI  - Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding
      proteins.
AB  - 14-3-3 proteins regulate the cell division cycle and play a pivotal role in
      blocking cell cycle advancement after activation of the DNA replication and DNA
      damage checkpoints. Here we describe a global proteomics analysis to identify
      proteins that bind to 14-3-3s during interphase and mitosis. 14-3-3-binding
      proteins were purified from extracts of interphase and mitotic HeLa cells using
      specific peptide elution from 14-3-3 zeta affinity columns. Proteins that
      specifically bound and eluted from the affinity columns were identified by
      microcapillary high pressure liquid chromatography tandem mass spectrometry
      analysis. Several known and novel 14-3-3-interacting proteins were identified in
      this screen. Identified proteins are involved in cell cycle regulation,
      signaling, metabolism, protein synthesis, nucleic acid binding, chromatin
      structure, protein folding, proteolysis, nucleolar function, and nuclear
      transport as well as several other cellular processes. In some cases 14-3-3
      binding was cell cycle-dependent, whereas in other cases the binding was shown to
      be cell cycle-independent. This study adds to the growing list of human 14-3-3
      binding proteins and implicates a role for 14-3-3 proteins in a plethora of
      essential biological processes.

PMID- 15161934
TI  - IC101 induces apoptosis by Akt dephosphorylation via an inhibition of heat shock
      protein 90-ATP binding activity accompanied by preventing the interaction with
      Akt in L1210 cells.
AB  - To find novel pharmacological tools useful for analyzing the molecular mechanism
      of apoptosis from natural resources, in the present study, we examined the
      activity of IC101, a cyclic depsipeptide isolated from Streptomyces sp. MJ202
      72F3, to induce apoptosis in the L1210 cell line. 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay showed that IC101 caused a concentration
      dependent cell death with a 50% effective concentration value of 20 nM. Cell
      shrinkage, chromatin condensation, a typical DNA ladder pattern, and up
      regulation of cleaved caspase-3 expression, which were biochemical
      characteristics of apoptosis, were induced by IC101. It also was observed that
      IC101 caused a concentration-dependent dephosphorylation of Akt and Bad without
      affecting phosphatidylinositol-3 kinase, an upstream molecule of Akt. IC101
      dephosphorylated the 90-kDa protein, as assayed by immunblotting of the cell
      extract by using anti-phosphotyrosine antibody. To identify the 90-kDa protein,
      immunoprecipitation and direct nano-flow liquid chromatography-tandem mass
      spectrometry (LC-MS) were performed to demonstrate that this protein was heat
      shock protein 90 (HSP90). Consistently, it was observed that IC101 induced the
      HSP90 tyrosine dephosphorylation by immunoblot analysis of immunoprecipitates
      with anti-HSP90 antibody using anti-phosphotyrosine antibody. IC101 caused the
      degradation of Raf-1, which formed a complex with HSP90. The HSP90-ATP binding
      also was inhibited by IC101 in a noncompetitive manner. An interaction of HSP90
      with Akt was shown to be inhibited by IC101 in a concentration-dependent manner.
      These results suggest that IC101 dephosphorylates Akt through an inhibition of
      HSP90 functions, resulting in the interaction with Akt to induce apoptotic cell
      death of L1210 cells.

PMID- 15161935
TI  - The modulating role of nuclear factor-kappaB in the action of alpha7-nicotinic
      acetylcholine receptor and cross-talk between 5-lipoxygenase and cyclooxygenase-2
      in colon cancer growth induced by 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1
      butanone.
AB  - 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific
      nitrosamine, induces lung cancer in all animal species tested and is thought to
      contribute significantly to the high lung cancer burden associated with smoking.
      However, there is no report whether NNK could promote colon cancer growth. To
      address this hypothesis and the possible signaling pathways involved, we used
      SW1116 colon cancer cell line to study these biological events in vitro. Results
      showed that NNK, after 5-h treatment, stimulated cell proliferation, enhanced
      alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) mRNA levels and nuclear
      factor-kappaB (NF-kappaB) DNA binding activity, as well as 5-lipoxygenase and
      cyclooxygenase-2 protein expressions. alpha-Bungarotoxin, the specific alpha7
      nAChR antagonist, inhibited these biological effects. However, 5-lipoxygenase
      inhibition had no effect on alpha7-nAChR mRNA expression, but significantly
      inhibited cell proliferation and activation of NF-kappaB and cyclooxygenase-2,
      whereas NF-kappaB-specific inhibitor caffeic acid phenethyl ester reduced both
      cell proliferation and cyclooxygenase expression induced by NNK without affecting
      alpha7-nAChR mRNA level and 5-lipoxygenase expression. Together, the present
      study demonstrated that NNK promoted colon cancer growth in vitro. NF-kappaB not
      only conveys the biological effect of alpha7-nAChR activation but is also
      involved in the cross-talk between 5-lipoxygenase and cyclooxygenase-2 in
      response to NNK in colon cancer cell development.

PMID- 15161936
TI  - Kaurene diterpene induces apoptosis in human leukemia cells partly through a
      caspase-8-dependent pathway.
AB  - Defects in apoptosis signaling pathways contribute to tumorigenesis and drug
      resistance, and these defects are often a cause of failure of chemotherapy. Thus,
      a major goal in chemotherapy is to find cytotoxic agents that restore the ability
      of tumor cells to undergo apoptosis. We previously found that an Ent-kaurene
      diterpene, Ent-11alpha-hydroxy-16-kauren-15-one (KD), induced apoptosis in human
      promyelocytic leukemia HL-60 cells. Here, we found that caspase-8, an apoptotic
      factor, is involved in KD-induced apoptosis. Although treatment of HL-60 cells
      with KD resulted in the activation of caspase-8 and -9, a caspase-8-specific
      inhibitor but not a caspase-9-specific inhibitor attenuated KD-induced apoptosis.
      Expression of a catalytically inactive caspase-8 partly attenuated KD-induced
      apoptosis. Treatment with KD led to a time-dependent cleavage of Bid, a substrate
      of caspase-8, as well as to the proteolytic processing of procaspase-8,
      indicating that KD treatment induces apoptosis through a caspase-8-dependent
      pathway. Moreover, overexpression of the drug resistance factor Bcl-2, which is
      frequently overexpressed in many tumors, failed to confer resistance to KD
      induced cytotoxicity. Thus, KD may be a promising experimental cytotoxic agent
      that possibly points to new strategies to overcome a drug resistance.

PMID- 15161937
TI  - Transient calnexin interaction confers long-term stability on folded K+ channel
      protein in the ER.
AB  - We recently showed that an unglycosylated form of the Shaker potassium channel
      protein is retained in the endoplasmic reticulum (ER) and degraded by proteasomes
      in mammalian cells despite apparently normal folding and assembly. These results
      suggest that channel proteins with a native structure can be substrates for ER
      associated degradation. We have now tested this hypothesis using the wild-type
      Shaker protein. Wild-type Shaker is degraded by cytoplasmic proteasomes when it
      is trapped in the ER and prevented from interacting with calnexin. Neither
      condition alone is sufficient to destabilize the protein. Proteasomal degradation
      of the wild-type protein is abolished when ER mannosidase I trimming of the core
      glycan is inhibited. Our results indicate that transient interaction with
      calnexin provides long-term protection from ER-associated degradation.

PMID- 15161938
TI  - Sensitization of Dictyostelium chemotaxis by phosphoinositide-3-kinase-mediated
      self-organizing signalling patches.
AB  - The leading edge of Dictyostelium cells in chemoattractant gradients can be
      visualized using green fluorescent protein (GFP) tagged to the pleckstrin
      homology (PH) domain of cytosolic regulator of adenylyl cyclase (CRAC), which
      presumable binds phosphatidylinositol-(3,4,5)triphosphate [PtdIns(3,4,5)P(3)].
      Uniform cyclic AMP (cAMP) concentrations induce persistent translocation of
      PH(Crac)-GFP from the cytosol to multiple patches, which are similar to the
      single patch of PH(Crac)-GFP at the leading edge in a cAMP gradient. We show that
      cAMP determines the probability of patch formation (half-maximal effect at 0.5 nM
      cAMP) but not the size, lifetime or intensity of patches, indicating that patches
      are self-organizing structures. A pseudopod is extended from the area of the cell
      with a PH(Crac)-GFP patch at about 10 seconds after patch formation. Cells
      treated with the F-actin inhibitor latrunculin A are round without pseudopodia;
      uniform cAMP still induces localized patches of PH(Crac)-GFP. Inhibition of
      phosphoinositide-3-kinase (PI3K) activity with LY294002 inhibits PH(Crac)-GFP
      patches and inhibits chemotaxis towards nanomolar cAMP but has no effect at
      higher cAMP concentrations. Thus, very low cAMP concentrations induce self
      organizing PH(Crac)-GFP patches that serve as a spatial cue for pseudopod
      formation, which enhances the sensitivity and amplitude of chemotactic movement.

PMID- 15161939
TI  - Differential localization of the centromere-specific proteins in the major
      centromeric satellite of Arabidopsis thaliana.
AB  - The 180 bp family of tandem repetitive sequences, which constitutes the major
      centromeric satellite in Arabidopsis thaliana, is thought to play important roles
      in kinetochore assembly. To assess the centromere activities of the 180 bp
      repeats, we performed indirect fluorescence immunolabeling with antibodies
      against phosphorylated histone H3 at Ser10, HTR12 (Arabidopsis centromeric
      histone H3 variant) and AtCENP-C (Arabidopsis CENP-C homologue) for the A.
      thaliana cell cultures. The immunosignals from all three antibodies appeared on
      all sites of the 180 bp repeats detected by fluorescence in situ hybridization.
      However, some of the 180 bp repeat clusters, particularly those that were long or
      stretched at interphase, were not fully covered with the signals from anti-HTR12
      or AtCENP-C. Chromatin fiber immunolabeling clearly revealed that the centromeric
      proteins examined in this study, localize only at the knobs on the extended
      chromatin fibers, which form a limited part of the 180 bp clusters. Furthermore,
      outer HTR12 and inner phosphohistone H3 (Ser10) localization at the kinetochores
      of metaphase chromosomes suggests that two kinds of histone H3 (a centromere
      variant and a phosphorylated form) might be linked to different roles in
      centromere functionality; the former for spindle-fiber attachment, and the latter
      for chromatid cohesion.

PMID- 15161940
TI  - Non-genomic regulation of transmitter release by retinoic acid at developing
      motoneurons in Xenopus cell culture.
AB  - Although the long-term effects of all-trans retinoic acid (RA) on neuronal growth
      and differentiation have been intensively studied, nothing is known about its
      effect on synaptic transmission. Here we show that RA rapidly and specifically
      enhances the spontaneous acetylcholine release at developing neuromuscular
      synapses in Xenopus cell culture using whole-cell patch-clamp recording. Acute
      addition of RA dose-dependently and reversibly enhances the frequency of
      spontaneous synaptic currents (SSCs). Application of the lipophilic RA analogue
      all-trans retinol or RA metabolites produced by light-induced decomposition
      failed to provoke similar changes in SSC frequency, indicating the specificity of
      RA-induced facilitation of spontaneous transmitter release. Protein synthesis
      inhibitors anisomycin or cycloheximide had no effect on RA-induced SSC frequency
      facilitation. Treating cells with pan RA receptor (RAR) selective agonist or
      RARbeta-selective agonist, but not RARalpha-, RARgamma- or retinoid X receptor
      (RXR)-selective agonists, mimicked the action of RA. These results suggest that
      RA acts through the activation of RARbeta, to induce a rapid, non-genomic
      increase in the frequency of spontaneous transmitter release at developing
      neuromuscular synapses.

PMID- 15161941
TI  - Carbohydrates act as sorting determinants in ER-associated degradation of
      tyrosinase.
AB  - The endoplasmic reticulum (ER) quality-control machinery maintains the fidelity
      of the maturation process by sorting aberrant proteins for ER-associated protein
      degradation (ERAD), a process requiring retrotranslocation from the ER lumen to
      the cytosol and degradation by the proteasome. Here, we assessed the role of N
      linked glycans in ERAD by monitoring the degradation of wild-type (Tyr) and
      albino mutant (Tyr(C85S)) tyrosinase. Initially, mutant tyrosinase was
      established as a genuine ERAD substrate using intact melanocyte and semi
      permeabilized cell systems. Inhibiting mannose trimming or accumulating Tyr(C85S)
      in a monoglucosylated form led to its stabilization, supporting a role for lectin
      chaperones in ER retention and proteasomal degradation. In contrast, ablating the
      lectin chaperone interactions by preventing glucose trimming caused a rapid
      disappearance of tyrosinase, initially due to the formation of protein
      aggregates, which were subsequently degraded by the proteasome. The co
      localization of aggregated tyrosinase with protein disulfide isomerase and BiP,
      but not calnexin, supports an ER organization, which aids in protein maturation
      and degradation. Based on these studies, we propose a model of tyrosinase
      degradation in which interactions between N-linked glycans and lectin chaperones
      help to minimize tyrosinase aggregation and also target non-native substrates for
      retro-translocation and subsequent degradation.

PMID- 15161942
TI  - The nucleolus is involved in mRNA export from the nucleus in fission yeast.
AB  - To elucidate the mechanism of mRNA export from the nucleus, we isolated five
      novel temperature-sensitive mutants (ptr7 to ptr11) that accumulate poly(A)(+)
      RNA in the nuclei at the nonpermissive temperature in Schizosaccharomyces pombe.
      Of those, the ptr11 mutation was found in the top2(+) gene encoding DNA
      topoisomerase II. In addition to the nuclear accumulation of poly(A)(+) RNA,
      ptr11 exhibited the cut (cell untimely torn) phenotype at the nonpermissive
      temperature, like the previously isolated mutant, ptr4. In these two mutants,
      cytokinesis occurred without prior nuclear division, resulting in cleavage of the
      undivided nuclei by the septum. To investigate the relationship between mRNA
      export defects and the cut phenotype observed in ptr4 and ptr11, we analyzed 11
      other mutants displaying the cut phenotype and found that all these tested
      mutants accumulate poly(A)(+) mRNA in the aberrantly cleaved nuclei.
      Interestingly, nuclear accumulation of poly(A)(+) mRNA was observed only in the
      anucleolate nuclei produced by aberrant cytokinesis. In addition, nuc1, the S.
      pombe mutant exhibiting a collapsed nucleolus, trapped poly(A)(+) mRNA in the
      nucleolar region at the nonpermissive temperature. In ptr11 and nuc1, mRNA
      transcribed from the intron-containing TBP gene showed nuclear accumulation, but
      not transcripts from the intron-less TBP cDNA, suggesting that the export pathway
      differs between the spliced and unspliced TBP mRNAs. These findings support the
      notion that a subset of mRNAs in yeast is exported from the nucleus through
      transient association with the nucleolus.

PMID- 15161943
TI  - A NHERF binding site links the betaPDGFR to the cytoskeleton and regulates cell
      spreading and migration.
AB  - The Na(+)/H(+) exchanger regulatory factor, NHERF, is a multifunctional adapter
      protein involved in a wide range of physiological activities. NHERF associates
      with merlin and the ezrin/radixin/moesin (MERM) family of membrane-actin
      cytoskeletal linker proteins through its C-terminus and is capable of interacting
      via its PDZ1 domain to the betaPDGF receptor (betaPDGFR). Thus, NHERF,
      potentially links the betaPDGFR to the actin cytoskeleton through its interaction
      with MERM proteins. In the present study, we have examined whether abolishing the
      interaction of betaPDGFR with NHERF results in actin cytoskeletal rearrangements.
      We have stably expressed a wild-type betaPDGFR, a mutant betaPDGFR (L1106A) that
      is incapable of interacting with NHERF, as well as a kinase defective mutant
      receptor (K634R), in PDGFR-deficient mouse embryonic fibroblasts. Our
      observations indicate that cells expressing betaPDGFR (L1106A) were impaired in
      their ability to spread and migrate on fibronectin compared with wild-type and
      K634R cells. L1106A mutant cells also revealed an increased number of focal
      adhesions, a condensed F-actin ring at the cell periphery and a decrease in total
      focal adhesion kinase (FAK) tyrosine phosphorylation. Further, we show that NHERF
      and MERM proteins could act as intermediary bridging proteins between betaPDGFR
      and FAK. Thus, the interaction of betaPDGFR with NHERF may provide an essential
      link between the cell membrane and the cortical actin cytoskeleton independent of
      receptor activity.

PMID- 15161944
TI  - Sequence-matched probes produce increased cross-platform consistency and more
      reproducible biological results in microarray-based gene expression measurements.
AB  - Cancer derived microarray data sets are routinely produced by various platforms
      that are either commercially available or manufactured by academic groups. The
      fundamental difference in their probe selection strategies holds the promise that
      identical observations produced by more than one platform prove to be more robust
      when validated by biology. However, cross-platform comparison requires matching
      corresponding probe sets. We are introducing here sequence-based matching of
      probes instead of gene identifier-based matching. We analyzed breast cancer cell
      line derived RNA aliquots using Agilent cDNA and Affymetrix oligonucleotide
      microarray platforms to assess the advantage of this method. We show, that at
      different levels of the analysis, including gene expression ratios and difference
      calls, cross-platform consistency is significantly improved by sequence- based
      matching. We also present evidence that sequence-based probe matching produces
      more consistent results when comparing similar biological data sets obtained by
      different microarray platforms. This strategy allowed a more efficient transfer
      of classification of breast cancer samples between data sets produced by cDNA
      microarray and Affymetrix gene-chip platforms.

PMID- 15161945
TI  - Phase IV trial evaluating the effectiveness and safety of dofetilide.
AB  - BACKGROUND: Dofetilide gained Food and Drug Administration approval for
      persistent atrial fibrillation/flutter (AFF) based on 2 randomized, placebo
      controlled, dose-ranging studies. Concerns of proarrhythmia have prompted the
      manufacturer to develop specific treatment guidelines. OBJECTIVE: To determine
      the effectiveness and safety of dofetilide in clinical practice as well as to
      ascertain whether clinicians are following established dosing guidelines.
      METHODS: This retrospective analysis evaluated guideline adherence and safety in
      patients who received dofetilide at a tertiary care medical center. Safety
      assessment included monitoring for the occurrence of excessive QTc interval
      prolongation and torsade de pointes. Excessive QTc interval prolongation was
      defined as >15% above baseline after the first dose or >500 msec following any
      dose (>550 msec in patients with ventricular conduction abnormalities). Patients
      were included in the effectiveness assessment if they received at least 36 hours
      of dofetilide for persistent AFF, received an appropriate dose per guidelines,
      and did not receive direct current cardioversion during the evaluation period. We
      compared the 36-hour conversion rate with dofetilide in this study with that
      observed in the EMERALD and SAFIRE-D trials using the Z test, and we evaluated
      the incidence of excessive QTc interval prolongation in high-risk subgroups by
      chi(2) analysis. RESULTS: Investigators identified 107 patients. The primary
      indication for dofetilide was AFF, with 58.9% receiving the drug for paroxysmal
      disease. Prescribing followed established guidelines, except that it was used
      intermittently by nonconfirmed prescribers (5.6%) and/or at inconsistent doses
      (14%). Excessive prolongation of the QTc interval occurred in 17.8% of patients
      after the first dose and 26.2% during subsequent doses; prolongation was more
      common in those with structural heart disease (p < 0.01). No patients developed
      torsade de pointes. In the effectiveness assessment (n = 25), the conversion of
      persistent AFF at 36 hours was higher than in previous studies (48% vs 27.2%; p =
      0.05). CONCLUSIONS: In clinical practice, the conversion of persistent AFF with
      dofetilide is at least comparable to premarketing studies, with a similar safety
      profile. Institutions should continue to emphasize adherence with established
      treatment guidelines.

PMID- 15161946
TI  - Mind your P's and Q's: transcription errors and elderly patients.

PMID- 15161948
TI  - Comment: use of epoetin alfa in critically ill patients.

PMID- 15161947
TI  - Reversible ageusia after chemotherapy with pegylated liposomal doxorubicin.
AB  - OBJECTIVE: To report a case of reversible ageusia in a patient with multiple
      myeloma receiving pegylated liposomal doxorubicin. CASE SUMMARY: A 67-year-old
      man with a history of arterial hypertension and persisting left bundle-branch
      block was diagnosed with multiple myeloma. He was initially treated with
      cyclophosphamide 200 mg/m(2) (days 1-4), pegylated liposomal doxorubicin 20
      mg/m(2) (day 1), and dexamethasone 40 mg (days 1-4) (CLAD). That treatment was
      followed by high-dose melphalan therapy and autologous peripheral stem-cell
      transplantation. The disease recurred 18 months later, and renal failure
      developed. The patient was again treated with the CLAD protocol. After the first
      cycle, almost complete ageusia occurred, along with weight loss and severe
      depression. Chemotherapy was continued, but pegylated liposomal doxorubicin was
      replaced by conventional doxorubicin. Within 12 weeks, the patient's sense of
      taste returned to normal. DISCUSSION: Pegylated liposomal anthracyclines are
      increasingly being used as a less cardiotoxic alternative to conventional
      doxorubicin in first- and second-line therapy of multiple myeloma. Whereas
      cardiotoxicity and unspecific reactions are seen less frequently, palmar-plantar
      erythrodysesthesia is a common reaction to pegylated liposomal anthracyclines. No
      other reasons for ageusia in our patient could be identified. Based on the
      Naranjo probability scale, ageusia was rated as a probable reaction to pegylated
      liposomal doxorubicin. CONCLUSIONS: As with all new and innovative drugs,
      thorough documentation of infrequent adverse events is necessary. We would like
      to raise awareness for ageusia, which appears to be a rare but severely impairing
      adverse reaction to a relatively new pharmacologic agent.

PMID- 15161949
TI  - Spiral laminar flow in the abdominal aorta: a predictor of renal impairment
      deterioration in patients with renal artery stenosis?
AB  - BACKGROUND: Spiral or helical arterial blood flow patterns have been widely
      observed in both animals and humans. The absence of spiral flow has been
      associated with carotid arterial disease. The aim of this study was to detect the
      presence of aortic spiral flow using magnetic resonance imaging (MRI) and to
      evaluate the relationship of the presence of spiral aortic flow with renal
      arterial disease and renal function in the follow-up of patients with suspected
      renal atheromatous disease. METHODS: Prospective study of 100 patients with
      suspected renal arterial disease and 44 patient controls. Using a 1.5 T MRI unit
      (Siemens Symphony), phase contrast flow quantification and three-dimensional
      contrast enhanced MR angiography of the abdominal aorta were performed. Renal
      arterial stenoses (RAS) were classified minimal, moderate or severe. Renal
      function was followed at 3 months before and 6 months after MRI. RESULTS: Non
      spiral flow was more prevalent in patients with more severe RAS. Renal impairment
      progressed significantly in severe RAS without spiral flow (P = 0.0065), but did
      not progress significantly in severe RAS with spiral flow (P = 0.12). In minimal
      or moderate RAS with or without spiral flow there was no significant progression
      (P = 0.16, 0.13, 0.47, 0.092, respectively). CONCLUSIONS: Aortic spiral blood
      flow can be assessed with MRI. Lack of aortic spiral blood flow in patients with
      severe RAS is associated with significant short-term renal function
      deterioration. Determination of blood flow patterns may be a useful indicator of
      renal impairment progression in patients with suspected renal artery stenosis.

PMID- 15161950
TI  - Clinical validation of glucose pump test (GPT) compared with ultrasound dilution
      technology in arteriovenous graft surveillance.
AB  - BACKGROUND: Blood flow (Qa) measurements are an important step in the
      surveillance protocol of haemodialysis vascular access (VA). The glucose pump
      test (GPT) is a new test for Qa measurement based on the dilution of a constant
      glucose infusion. The aim of this study is to verify the clinical accuracy of GPT
      in a graft surveillance protocol with sequential Qa measurements. METHODS: In 30
      chronic haemodialysis patients with graft, we compared monthly sequential Qa
      measurements performed with GPT in pre-dialysis and the ultrasound dilution
      technique (HD01 device Transonic Systems Inc., USA) during dialysis. The colour
      Doppler ultrasonography study (CDU) was our reference standard for the diagnosis
      of stenosis. The endpoints were the graft thrombosis or PTA treatment. RESULTS:
      According to the K/DOQI guidelines we could identify the thrombosis high-risk
      grafts when Qa was <600 ml/min or <1000 ml/min with a decrease >25% in serial Qa
      measurements. HD01 yielded 27 of 112 high-risk Qa measurements (21 Qa <600
      ml/min; mean 406+/-145 ml/min; 6 deltaQa >25%; mean 43+/-7%). In 12 of 27 cases
      the CDU control did not show haemodynamically significant stenoses (false
      positive); 15 of 27 cases were confirmed high-risk accesses by CDU and did PTAs
      (HD01 specificity 86%). GPT yielded 14 of 112 high-risk Qa measurements (8 Qa
      <600 ml/min; mean 404+/-135 ml/min; 6 deltaQa >25%; mean 38+/-8%) and all had
      severe stenoses and underwent PTA treatments showing a GPT specificity of 100%.
      The CDU study allowed us to correctly assess the Qa negative cases. HD01 method
      had 10 false negative cases (treated or clotted grafts with a Qa >600 ml/min and
      deltaQa <25%) with a sensitivity of 60%, while GPT had 11 false negative cases
      with a sensitivity of 56%. The diagnostic accuracy tested with the ROC curves was
      similar with both tests (area under the curve was 0.762 and 0.752 with GPT and
      ultrasound dilution, respectively; P = 0.985). The diagnostic efficiency
      (percentage of grafts with agreement between test result and factual situation)
      was 90 and 80% (P = 0.056) for GPT and HD01, respectively. CONCLUSION: Compared
      with HD01, the GPT had a lower false positive rate and similar diagnostic
      accuracy and efficiency. The clinical implication is a smaller number of
      unnecessary, invasive procedures (angiographies or PTAs), without increasing the
      thrombosis risk. This study has shown that GPT is an accurate, quick and economic
      test for Qa monitoring.

PMID- 15161951
TI  - Rapid microalbuminuria screening in type 2 diabetes mellitus: simplified approach
      with Micral test strips and specific gravity.
AB  - BACKGROUND: Microalbuminuria is known to be a harbinger of serious complications
      in type 2 diabetes mellitus. Since medical intervention at the onset of
      microalbuminuria can be critical in reducing these adverse outcomes, it is widely
      agreed that type 2 diabetic patients should be screened for microalbuminuria. The
      purpose of the present study is to evaluate Micral test strips in conjunction
      with a urine specific gravity determination as a rapid and accurate method for
      detecting microalbuminuria in type 2 diabetic patients. METHODS: In this
      prospective study, a total of 444 urine samples of type 2 diabetic patients were
      obtained from the ABCD study cohort for analysis. Urinary albumin concentrations
      were determined using Micral test strips and compared to results measuring
      albumin by the immunoturbidimetry method of timed collections. Urine specific
      gravity was measured by a standard urine dipstick. RESULTS: The performance
      characteristics of the Micral test strips for detecting microalbuminuria (30-300
      mg albumin/24 h) were adequate but not optimal: sensitivity 88%, specificity 80%,
      positive predictive value 69%, negative predictive value 92%. A concomitant
      specific gravity determination was useful in indexing the magnitude of false
      negative and false positive readings by the Micral test strips. CONCLUSIONS:
      While the use of Micral test strips provides a rapid approach to detecting
      microalbuminuria in type 2 diabetic patients, this method has limitations. The
      simultaneous measurement of specific gravity is helpful in addressing some of the
      shortcomings of this screening test.

PMID- 15161952
TI  - Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. Part II-
      Kidney hypertrophy and calcium deposition.
AB  - BACKGROUND: Kidney hypertrophy is stimulated by both partial nephrectomy and
      NH(4)Cl administration. Also, parathyroidectomy (PTX) has been reported to
      prevent kidney hypertrophy induced by a high protein diet. Our goal was to
      determine in the azotaemic rat: (i) the combined effects of NH(4)Cl
      administration and dietary phosphorus on the development of kidney hypertrophy
      and calcium deposition in the kidney and (ii) whether the absence of parathyroid
      hormone (PTH) affected the development of kidney hypertrophy and calcium
      deposition. METHODS: High (HPD, 1.2%), normal (NPD, 0.6%) or low (LPD, <0.05%)
      phosphorus diets were given to 5/6 nephrectomized rats for 30 days. In each
      dietary group, one-half of the rats were given NH(4)Cl in the drinking water. The
      six groups of rats were: (i) HPD + NH(4)Cl; (ii) HPD; (iii) NPD + NH(4)Cl; (iv)
      NPD; (v) LPD + NH(4)Cl and (vi) LPD. In a separate study, PTX was performed to
      determine whether PTH affected renal hypertrophy in 5/6 nephrectomized rats given
      NH(4)Cl. RESULTS: Both with and without NH(4)Cl (+/-NH(4)Cl), kidney weight was
      greatest (P<0.05) in the HPD groups. In each dietary phosphorus group, kidney
      weight was greater (P<0.05) in the NH(4)Cl group. In both the +/-NH(4)Cl groups,
      kidney calcium content was greatest (P<0.05) in the HPD group, but was less
      (P<0.05) in the NPD and HPD groups given NH(4)Cl. An inverse correlation was
      present between creatinine clearance and kidney calcium content (r = -0.51,
      P<0.001). When factored for kidney weight, creatinine clearance was less (P<0.05)
      in the HPD group in both the +/-NH(4)Cl groups, but was greater in the HPD +
      NH(4)Cl than in the HPD group. In PTX rats, kidney weight was greater (P<0.05)
      and kidney calcium deposition was less (P<0.05) in rats given NH(4)Cl.
      CONCLUSIONS: In azotaemic rats studied for 30 days, NH(4)Cl administration
      induced kidney hypertrophy. A HPD also induced kidney hypertrophy. The effects on
      kidney calcium deposition were divergent for which NH(4)Cl administration
      decreased and a HPD increased calcium deposition. The inverse correlation between
      kidney calcium content and creatinine clearance suggests that kidney calcium
      deposition is harmful to renal function. When factored for kidney weight, the
      lower creatinine clearance in the high phosphorus group suggests that kidney
      hypertrophy does not completely compensate for the harmful effects of a HPD. This
      result also suggests that a longer study would probably result in more rapid
      deterioration in the high phosphorus group. In PTX rats, the absence of PTH did
      not prevent NH(4)Cl from inducing kidney hypertrophy and reducing kidney calcium
      deposition. In conclusion, NH(4)Cl and dietary phosphorus each independently
      affect kidney growth and calcium deposition in the growing rat with renal
      failure.

PMID- 15161953
TI  - Predictors of haemodynamic instability and heart rate variability during
      haemodialysis.
AB  - BACKGROUND: The pathogenesis of haemodialysis-induced hypotension is
      multifactorial and may include autonomic nervous system dysfunction. The present
      study was undertaken to (i) determine heart rate variability (HRV) in chronic
      haemodialysis patients without and with haemodynamic instability (hypotension
      prone) during ultrafiltration and (ii) identify patients at risk and the
      predictors of dialysis-related hypotension. METHODS: HRV was evaluated in 56
      chronic haemodialysis patients without (stable; n = 27) and with symptomatic
      hypotension episodes (unstable; n = 29) during daytime, haemodialysis and night
      time periods. Logistic regression analysis was performed in a model that included
      clinical and biochemical data and HRV measurements. RESULTS: HRV was
      significantly reduced in haemodynamically unstable as compared with the stable
      patients. LF/HF ratio, an index representative of sympathovagal balance, was
      significantly lower in unstable patients, especially in those with ischaemic
      heart disease and diabetes mellitus. In a logistic regression model including
      clinical data and HRV measurements, ischaemic heart disease and left ventricular
      systolic dysfunction were found to be the main predictors of haemodynamic
      instability. CONCLUSIONS: These data suggest that haemodynamic instability is
      strongly associated with a decreased HRV and an impaired sympathovagal balance,
      suggesting disturbed autonomic control in uraemic patients with cardiac damage.
      Patients with ischaemic heart disease, reduced left ventricular systolic function
      and decreased HRV may be at the highest risk to be haemodynamically unstable
      during haemodialysis. The role of early detection and treatment of ischaemic
      heart disease in preventing symptomatic hypotensive episodes in these patients
      remains to be determined.

PMID- 15161954
TI  - Treatment options for IgA nephropathy in adults: a proposal for evidence-based
      strategy.

PMID- 15161955
TI  - Sleep disorders and illness intrusiveness in patients on chronic dialysis.
AB  - BACKGROUND: The prevalence of sleep problems (insomnia, restless legs syndrome,
      periodic limb movements in sleep and sleep apnoea) has been shown to be high in
      patients with end-stage renal disease (ESRD) and might contribute to impaired
      quality of life in this population. METHODS: In a cross-sectional study using
      self-administered questionnaires, we examined the prevalence of sleep disorders
      and assessed their effect on different aspects of health-related quality of life
      in a sample of Hungarian patients on maintenance dialysis. RESULTS: Our data
      confirm that sleep problems are frequent in patients with ESRD; 65% of the
      patients reported symptoms of at least one specific sleep disorder; insomnia was
      the most common sleep complaint with 49%, the prevalence of sleep apnoea was 32%
      and the prevalence of restless legs syndrome was 15%. Co-morbidity, assessed by
      the End-Stage Renal Disease Severity Index, was shown to be an independent
      predictor of sleep disorders. Patients with sleep disorders reported higher
      illness intrusiveness and worse self-perceived health than those without sleep
      problems. The presence of sleep disorders was an independent predictor of illness
      intrusiveness, an important determinant of health-related quality of life.
      CONCLUSION: Sleep disorders are important determinants of illness intrusiveness
      and health-related quality of life in patients with ESRD. Sleep problems may be
      treated successfully; therefore, more attention should be paid to assessing these
      problems in this patient population.

PMID- 15161956
TI  - A randomized controlled trial of immunosuppression conversion for the treatment
      of chronic allograft nephropathy.
AB  - BACKGROUND: This study was conducted to assess the effect of immunosuppression
      conversion on progression of chronic allograft nephropathy (CAN). METHODS: Forty
      two cyclosporin-treated renal transplant recipients were studied. Patients were
      included if they had a negatively sloping reciprocal of creatinine vs time (ROCT)
      plot for >6 months and biopsy-proven CAN. Patients were excluded if they had
      previously been treated with tacrolimus/mycophenolate mofetil (MMF) or their
      serum creatinine was >400 micromol/l. Subjects were randomly treated with either:
      (A) MMF/reduced dose cyclosporin [MMF for azathioprine 0.5-1.0 g bd; cyclosporin
      trough level (C(0)): 75-100 ng/ml]; (B) tacrolimus for cyclosporin (C(0): 5-10
      ng/ml); or (C) continuation of standard therapy. Glomerular filtration rate (GFR)
      was measured at baseline and after 6 months. RESULTS: Two patients started
      dialysis within 6 months (one each from groups A and B). One patient in group A
      was intolerant of MMF, six others reported gastrointestinal symptoms and three
      developed anaemia. Cyclosporin dose was reduced by 24% [interquartile range
      (IQR): 14-27%] in group A [end-of-study C(0): 99 ng/ml (IQR: 90-113 ng/ml)]. In
      group B, the end-of-study tacrolimus C(0) was 7 ng/ml (5-9 ng/ml). The end-of
      study cyclosporin C(0) in group C was 163 ng/ml (145-215 ng/ml). Comparison of
      ROCT slopes before and after intervention revealed a treatment advantage for
      group A (P<0.05). The GFR analysis was supportive (P = 0.05). When patients with
      GFR <20 ml/min/1.73 m(2) at enrollment were excluded from the analysis, the
      treatment advantage for group A reached statistical significance (n = 27,
      P<0.05). CONCLUSIONS: MMF/reduced dose cyclosporin is superior to tacrolimus-for
      cyclosporin and standard dose cyclosporin in patients with CAN, at least in the
      short term. The cyclosporin dose reduction component is likely to be of
      particular importance. Other findings suggest that early intervention is
      beneficial.

PMID- 15161958
TI  - Characterization of critical interactions between Ndt80 and MSE DNA defining a
      novel family of Ig-fold transcription factors.
AB  - The Ndt80 protein of the yeast Saccharomyces cerevisiae is the founding member of
      a new sub-family of proteins in the Ig-fold superfamily of transcription factors.
      The crystal structure of Ndt80 bound to DNA shows that it makes contacts through
      several loops on one side of the protein that connect beta-strands which form the
      beta-sandwich fold common to proteins in this superfamily. However, the DNA
      binding domain of Ndt80 is considerably larger than many other members of the Ig
      fold superfamily and it appears to make a larger number of contacts with the DNA
      than these proteins. To determine the contribution of each of these contacts and
      to examine if the mechanism of Ndt80 DNA binding was similar to other members of
      the Ig-fold superfamily, amino acid substitutions were introduced at each residue
      that contacts the DNA and assayed for their effect on Ndt80 activity. Many of the
      mutations caused significant decreases in DNA-binding affinity and
      transcriptional activation. Several of these are in residues that are not found
      in other sub-families of Ig-fold proteins. These additional contacts are likely
      responsible for Ndt80's ability to bind DNA as a monomer while most other members
      require additional domains or cofactors to recognize their sites.

PMID- 15161959
TI  - Coupled amplification and degradation of exogenous RNA injected in amphibian
      oocytes.
AB  - The early development of amphibians takes place in the absence of significant
      transcription and is controlled at the post-transcriptional level. We have
      reported that in vitro synthesized transcripts injected into axolotl fertilized
      eggs or oocytes were not continuously degraded as their abundance apparently
      fluctuated over time, with detected amounts sometimes higher than initial
      injected amounts. To further characterize this phenomenon, we have co-injected
      RNA chain terminators to prevent RNA synthesis. This led to the suppression of
      fluctuations and to a regular decrease in the amount of transcripts that appeared
      to be more stable in the presence of inhibitors. These observations indicate a
      coupling between RNA synthesis and an accelerated degradation. Throughout the
      time course, cRNA molecules could be detected, and their abundance increased in
      the early phase of the kinetics, supporting the implication of an RNA-dependent
      RNA polymerase in an asymmetric amplification process. Finally, when the fate of
      the injected transcripts was investigated in individual oocytes, we observed an
      absolute increase in abundance in some but not all oocytes, supporting the
      existence of a limiting step in the initiation of the RNA amplification
      stochastic process.

PMID- 15161957
TI  - The ribosomal RNA gene promoter and adjacent cis-acting DNA sequences govern
      plasmid DNA partitioning and stable inheritance in the parasitic protozoan
      Leishmania.
AB  - Detailed analysis of the Leishmania donovani ribosomal RNA (rRNA) gene promoter
      region has allowed the identification of cis-acting sequences involved in plasmid
      DNA partitioning and stable plasmid inheritance. We report that plasmids bearing
      the 350 bp rRNA promoter along with the 200 bp region immediately 3' to the
      promoter exhibited a 6.5-fold increase in transformation frequency and were
      transmitted to daughter cells as single-copy molecules. This is in contrast to
      what has been observed for plasmid molecules in this organism so far. Moreover,
      we show that these low-copy-number plasmids displayed a remarkable mitotic
      stability in the absence of selective pressure. The region in the vicinity of the
      RNA pol I transcription initiation site, and also in the adjacent 200 nt,
      displays a complex structural organization and shares sequence similarity to the
      yeast autonomously replicating consensus sequence and centromere DNA elements.
      Deletion analyses indicated that these elements were necessary but not sufficient
      for plasmid DNA partitioning and stable inheritance, and that the rRNA promoter
      region was required for optimal function. These results suggest an interplay
      between RNA pol I transcription, DNA replication, DNA partitioning and mitotic
      stability in trypanosomatids. This is the first example of defined DNA elements
      for plasmid partitioning and stable inheritance in the protozoan parasite
      Leishmania.

PMID- 15161960
TI  - Ligation activity of fragmented ribozymes in frozen solution: implications for
      the RNA world.
AB  - A vexing difficulty of the RNA world hypothesis is how RNA molecules of
      significant complexity could ever have evolved given their susceptibility to
      degradation. One way degradation might have been reduced is through low
      temperature. Here we report that truncated and fragmented derivatives of the
      hairpin ribozyme can catalyze ligation of a wide variety of RNA molecules to a
      given sequence in frozen solution despite having little or no activity under
      standard solution conditions. These results suggest that complex RNAs could have
      evolved in freezing environments on the early earth and perhaps elsewhere.

PMID- 15161961
TI  - Silencing of hydroxycinnamoyl-coenzyme A shikimate/quinate
      hydroxycinnamoyltransferase affects phenylpropanoid biosynthesis.
AB  - The hydroxyl group in the 3-position of the phenylpropanoid compounds is
      introduced at the level of coumarate shikimate/quinate esters, whose synthesis
      implicates an acyltransferase activity. Specific antibodies raised against the
      recombinant tobacco (Nicotiana tabacum) acyltransferase revealed the accumulation
      of the enzyme in stem vascular tissues of tobacco, in accordance with a putative
      role in lignification. For functional analysis, the acyltransferase gene was
      silenced in Arabidopsis thaliana and N. benthamiana by RNA-mediated
      posttranscriptional gene silencing. In Arabidopsis, gene silencing resulted in a
      dwarf phenotype and changes in lignin composition as indicated by histochemical
      staining. An in-depth study of silenced N. benthamiana plants by immunological,
      histochemical, and chemical methods revealed the impact of acyltransferase
      silencing on soluble phenylpropanoids and lignin content and composition. In
      particular, a decrease in syringyl units and an increase in p-hydroxyphenyl units
      were recorded. Enzyme immunolocalization by confocal microscopy showed a
      correlation between enzyme accumulation levels and lignin composition in vascular
      cells. These results demonstrate the function of the acyltransferase in
      phenylpropanoid biosynthesis.

PMID- 15161962
TI  - The Arabidopsis mutant sleepy1gar2-1 protein promotes plant growth by increasing
      the affinity of the SCFSLY1 E3 ubiquitin ligase for DELLA protein substrates.
AB  - DELLA proteins restrain the cell proliferation and enlargement that characterizes
      the growth of plant organs. Gibberellin stimulates growth via 26S proteasome
      dependent destruction of DELLAs, thus relieving DELLA-mediated growth restraint.
      Here, we show that the Arabidopsis thaliana sleepy1gar2-1 (sly1gar2-1) mutant
      allele encodes a mutant subunit (sly1gar2-1) of an SCF(SLY1) E3 ubiquitin ligase
      complex. SLY1 (the wild-type form) and sly1gar2-1 both confer substrate
      specificity on this complex via specific binding to the DELLA proteins. However,
      sly1gar2-1 interacts more strongly with the DELLA target than does SLY1. In
      addition, the strength of the SCFSLY1-DELLA interaction is increased by target
      phosphorylation. Growth-promoting DELLA destruction is dependent on SLY1
      availability, on the strength of the interaction between SLY1 and the DELLA
      target, and on promotion of the SCFSLY1-DELLA interaction by DELLA
      phosphorylation.

PMID- 15161965
TI  - Real-time RT-PCR analysis of housekeeping genes in human skeletal muscle
      following acute exercise.
AB  - Studies examining gene expression with RT-PCR typically normalize their mRNA data
      to a constitutively expressed housekeeping gene. The validity of a particular
      housekeeping gene must be determined for each experimental intervention. We
      examined the expression of various housekeeping genes following an acute bout of
      endurance (END) or resistance (RES) exercise. Twenty-four healthy subjects
      performed either a interval-type cycle ergometry workout to exhaustion (
      approximately 75 min; END) or 300 single-leg eccentric contractions (RES). Muscle
      biopsies were taken before exercise and 3 h and 48 h following exercise. Real
      time RT-PCR was performed on beta-actin, cyclophilin (CYC), glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), and beta2-microglobulin (beta2M). In a second
      study, 10 healthy subjects performed 90 min of cycle ergometry at approximately
      65% of Vo(2 max), and we examined a fifth housekeeping gene, 28S rRNA, and
      reexamined beta2M, from muscle biopsy samples taken immediately postexercise. We
      showed that CYC increased 48 h following both END and RES exercise (3- and 5
      fold, respectively; P < 0.01), and 28S rRNA increased immediately following END
      exercise (2-fold; P = 0.02). beta-Actin trended toward an increase following END
      exercise (1.85-fold collapsed across time; P = 0.13), and GAPDH trended toward a
      small yet robust increase at 3 h following RES exercise (1.4-fold; P = 0.067). In
      contrast, beta2M was not altered at any time point postexercise. We conclude that
      beta2M and beta-actin are the most stably expressed housekeeping genes in
      skeletal muscle following RES exercise, whereas beta2M and GAPDH are the most
      stably expressed following END exercise.

PMID- 15161964
TI  - Increased measurement accuracy for sequence-verified microarray probes.
AB  - Microarrays have been extensively used to investigate genome-wide expression
      patterns. Although this technology has been tremendously successful, it has
      suffered from suboptimal individual measurement precision. Significant
      improvements in this respect have been recently made. In an effort to further
      explore the underlying variability, we have attempted to globally assess the
      accuracy of individual probe sequences used to query gene expression. For
      mammalian Affymetrix microarrays, we identify an unexpectedly large number of
      probes (greater than 19% of the probes on each platform) that do not correspond
      to their appropriate mRNA reference sequence (RefSeq). Compared with data derived
      from inaccurate probes, we find that data derived from sequence-verified probes
      show 1) increased precision in technical replicates, 2) increased accuracy
      translating data from one generation microarray to another, 3) increased accuracy
      translating data from oligonucleotide to cDNA microarrays, and 4) improved
      capture of biological information in human clinical specimens. The logical
      conclusion of this work is that probes containing the most reliable sequence
      information provide the most accurate results. Our data reveal that the
      identification and removal of inaccurate probes can significantly improve this
      technology.

PMID- 15161963
TI  - Proteomic identification of annexins, calcium-dependent membrane binding proteins
      that mediate osmotic stress and abscisic acid signal transduction in Arabidopsis.
AB  - Comparative proteomic analysis of the Arabidopsis thaliana root microsomal
      fraction was performed to identify novel components of salt stress signaling.
      Among the salt-responsive microsomal proteins, two spots that increased upon salt
      treatment on a two-dimensional gel were identified as the same protein,
      designated annexin 1 (AnnAt1). Annexins comprise a multigene family of Ca2+
      dependent membrane binding proteins and have been extensively studied in animal
      cells. AnnAt1 is strongly expressed in root but rarely in flower tissue. In this
      study, the results suggest that salt stress induces translocation from the
      cytosol to the membrane and potential turnover of existing protein. This process
      is blocked by EGTA treatment, implying that AnnAt1 functions in stress response
      are tightly associated with Ca2+. T-DNA insertion mutants of annAt1 and a
      different isoform, annAt4, displayed hypersensitivity to osmotic stress and
      abscisic acid (ABA) during germination and early seedling growth. The results
      collectively suggest that AnnAt1 and AnnAt4 play important roles in osmotic
      stress and ABA signaling in a Ca2+-dependent manner.

PMID- 15161966
TI  - Genetic linkage of albuminuria and renal injury in Dahl salt-sensitive rats on a
      high-salt diet: comparison with spontaneously hypertensive rats.
AB  - Our aim was to study the effects of high-salt diet on the genetics of albuminuria
      and renal injury in the Dahl salt-sensitive (SS) rat. We compared SS with salt
      resistant spontaneously hypertensive rats (SHR) and with genetically related salt
      sensitive stroke-prone SHR (SHRSP). Moreover, we performed genome-wide linkage
      analysis to identify quantitative trait loci (QTL) contributing to salt-induced
      renal injury in an F2 population derived from SS and SHR (n = 230). In response
      to high-salt diet SS and SHRSP developed a striking increase in systolic blood
      pressure, urinary albumin excretion (UAE), and renal damage indices compared with
      SHR. Both SHRSP and SS developed severe glomerulosclerosis, whereas
      microangiopathy, tubulointerstitial fibrosis, and inflammation were more
      pronounced in SHRSP. We detected two QTL with significant linkage to UAE on rat
      chromosomes (RNO) 6 and 19. Comparison with the recently identified salt
      independent UAE QTL in young animals revealed that the UAE QTL on RNO6 is unique
      to high-salt conditions, whereas RNO19 plays a significant role during both low-
      and high-salt conditions. Some F2 animals demonstrated severe microangiopathy and
      tubulointerstitial injury, which exceeded the degree observed in the parental SS
      strain. Three loci demonstrated suggestive linkage to these phenotypes on RNO3,
      RNO5, and RNO20, whereas no linkage to glomerular damage was found. Further
      analyses at these loci indicated that the severity of renal injury was
      attributable to the SHR allele. Our data suggest that the SHR genetic background
      confers greater susceptibility for the development of microangiopathy and
      tubulointerstitial injury in salt-sensitive hypertension than the SS background.

PMID- 15161967
TI  - Glycan arrays lead to the discovery of autoimmunogenic activity of SARS-CoV.
AB  - Using carbohydrate microarrays, we characterized the carbohydrate binding
      activity of SARS-CoV neutralizing antibodies elicited by an inactivated SARS-CoV
      vaccine. In these antibodies, we detected undesired autoantibody reactivity
      specific for the carbohydrate moieties of an abundant human serum glycoprotein
      asialo-orosomucoid (ASOR). This observation provides important clues for the
      selection of specific immunologic probes to examine whether SARS-CoV expresses
      antigenic structures that mimic the host glycan. We found that lectin PHA-L
      (Phaseolus vulgaris L.), which is specific for a defined complex carbohydrate of
      ASOR, stained the SARS-CoV-infected cells specifically and intensively. Taken
      together, we present immunologic evidence that a carbohydrate structure of SARS
      CoV shares antigenic similarity with host glycan complex carbohydrates. The
      experimental approaches we applied in this study are likely applicable for the
      identification of immunologic targets of other viral pathogens.

PMID- 15161969
TI  - Ancient polyploidization predating divergence of the cereals, and its
      consequences for comparative genomics.
AB  - Integration of structural genomic data from a largely assembled rice genome
      sequence, with phylogenetic analysis of sequence samples for many other taxa,
      suggests that a polyploidization event occurred approximately 70 million years
      ago, before the divergence of the major cereals from one another but after the
      divergence of the Poales from the Liliales and Zingiberales. Ancient
      polyploidization and subsequent "diploidization" (loss) of many duplicated gene
      copies has thus shaped the genomes of all Poaceae cereal, forage, and biomass
      crops. The Poaceae appear to have evolved as separate lineages for approximately
      50 million years, or two-thirds of the time since the duplication event.
      Chromosomes that are predicted to be homoeologs resulting from this ancient
      duplication event account for a disproportionate share of incongruent loci found
      by comparison of the rice sequence to a detailed sorghum sequence-tagged site
      based genetic map. Differential gene loss during diploidization may have
      contributed many of these incongruities. Such predicted homoeologs also account
      for a disproportionate share of duplicated sorghum loci, further supporting the
      hypothesis that the polyploidization event was common to sorghum and rice.
      Comparative gene orders along paleo-homoeologous chromosomal segments provide a
      means to make phylogenetic inferences about chromosome structural rearrangements
      that differentiate among the grasses. Superimposition of the timing of major
      duplication events on taxonomic relationships leads to improved understanding of
      comparative gene orders, enhancing the value of data from botanical models for
      crop improvement and for further exploration of genomic biodiversity. Additional
      ancient duplication events probably remain to be discovered in other angiosperm
      lineages.

PMID- 15161970
TI  - Two Creutzfeldt-Jakob disease agents reproduce prion protein-independent
      identities in cell cultures.
AB  - Human Creutzfeldt-Jakob disease (CJD) and similar neurodegenerative diseases such
      as sheep scrapie are caused by a variety of related infectious agents. They are
      associated with abnormal host prion protein (PrP), which is assessed by limited
      proteolysis to yield resistant PrP bands (PrP-res). Although PrP-res has been
      posited as the infectious agent, purified PrP-res itself is not infectious. To
      establish the independence of CJD agent characteristics from those of PrP-res,
      two different mouse-passaged CJD strains were propagated in neuronal cell lines
      whose PrP-res patterns differ markedly from each other and from those found in
      infected brain. In mouse brain, the fast CJD strain, FU, elicits many PrP-res
      deposits, whereas the slow SY strain elicits few. Both strains evoked PrP-res in
      cultured murine cells, although SY induced PrP-res only transiently. PrP-res
      patterns in FU- and SY-infected GT1 cells were identical, and were significantly
      different from those in brain and in N2a cells. Nevertheless, all FU-infected
      cell lines reproduced their original fast disease in mice, even after extensive
      subculture, whereas SY-infected cells produced only slow disease. These data
      indicate PrP-res neither encodes nor alters agent-specific characteristics. PrP
      res was also a poor predictor of infectivity because SY cells that had lost PrP
      res were approximately 10-fold more infectious than PrP-res-positive cultures.
      Furthermore, FU titers increased 650-fold, whereas PrP-res remained constant.
      Passaged FU-infected cells had titers comparable to brain, and >30% of cells
      displayed abundant cytoplasmic PrP-res aggregates that may trap agent. The
      continuous substantial replication of CJD in monotypic cells will further the
      discrimination of agent-specific molecules from pathological host responses to
      infection.

PMID- 15161968
TI  - Long-range patterns of diversity and linkage disequilibrium surrounding the maize
      Y1 gene are indicative of an asymmetric selective sweep.
AB  - Both yellow and white corn occurs among ancestral open pollinated varieties. More
      recently, breeders have selected yellow endosperm variants of maize over
      ancestral white phenotypes for their increased nutritional value resulting from
      the up-regulation of the Y1 phytoene synthase gene product in endosperm tissue.
      As a result, diversity within yellow maize lines at the Y1 gene is dramatically
      decreased as compared to white corn. We analyzed patterns of sequence diversity
      and linkage disequilibrium in nine low copy regions located at varying distances
      from the Y1 gene, including a homolog of the barley Mlo gene. Patterns consistent
      with a selective sweep, such as significant associations of informative single
      nucleotide polymorphisms with endosperm color phenotype, linkage disequilibrium,
      and significantly reduced diversity within the yellow endosperm haplotypes, were
      observed up to 600 kb downstream of Y1, whereas the upstream region showed a more
      rapid recovery. The starch branching enzyme 1 (sbe1) gene is the first region
      downstream of Y1 that does not have a highly conserved haplotype in the yellow
      endosperm germplasm.

PMID- 15161971
TI  - Bile acids are essential for porcine enteric calicivirus replication in
      association with down-regulation of signal transducer and activator of
      transcription 1.
AB  - A porcine enteric calicivirus (PEC), strain Cowden in the family Caliciviridae
      (genus Sapovirus), can be propagated in a continuous cell line, LLC-PK cells, but
      only in the presence of an intestinal content fluid filtrate from gnotobiotic
      pigs. This cell culture system is presently the only in vitro model among
      caliciviruses that cause gastrointestinal disease, including members of the
      genera Sapovirus and Norovirus. We report here the identification of bile acids
      as active factors in intestinal content fluid essential for PEC growth. Bile
      acids that allowed PEC growth induced an increase in cAMP concentration in LLC-PK
      cells that was associated with down-regulation of IFN-mediated signal transducer
      and activator of transcription 1 phosphorylation, a key element in innate
      immunity. In addition, cAMP/protein kinase A pathway inhibitors, suramin,
      MDL12330A, or H89 suppressed bile acid-mediated PEC replication. We propose a
      mechanism for enteric calicivirus growth dependent on bile acids, ubiquitous
      molecules present in the intestine at the site of the virus replication that
      involves the protein kinase A cell-signaling pathway and a possible down
      regulation of innate immunity.

PMID- 15161973
TI  - Heme axial methionine fluxionality in Hydrogenobacter thermophilus cytochrome
      c552.
AB  - The heme group in paramagnetic (S = 1/2) ferricytochromes c typically displays a
      markedly asymmetric distribution of unpaired electron spin density among the heme
      pyrrole beta substituents. This asymmetry is determined by the orientations of
      the heme axial ligands, histidine and methionine. One exception to this is
      ferricytochrome c(552) from Hydrogenobacter thermophilus, which has similar
      amounts of unpaired electron spin density at the beta substituents on all four
      heme pyrroles. Here, determination of the orientation of the magnetic axes and
      analysis of NMR line shapes for H. thermophilus ferricytochrome c(552) is
      performed. These data reveal that the unusual electronic structure for this
      protein is a result of fluxionality of the heme axial methionine. It is proposed
      that the ligand undergoes inversion at the pyramidal sulfur, and the rapid
      interconversion between two diastereomeric forms results in the unusual heme
      electronic structure. Thus a fluxional process for a metal-bound amino acid side
      chain has now been identified.

PMID- 15161972
TI  - A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect
      telomere length.
AB  - Telomeres are nucleoprotein structures present at the ends of eukaryotic
      chromosomes that play a central role in guarding the integrity of the genome by
      protecting chromosome ends from degradation and fusion. Length regulation is
      central to telomere function. To broaden our knowledge about the mechanisms that
      control telomere length, we have carried out a systematic examination of
      approximately 4,800 haploid deletion mutants of Saccharomyces cerevisiae for
      telomere-length alterations. By using this screen, we have identified >150
      candidate genes not previously known to affect telomere length. In two-thirds of
      the identified mutants, short telomeres were observed; whereas in one-third,
      telomeres were lengthened. The genes identified are very diverse in their
      functions, but certain categories, including DNA and RNA metabolism, chromatin
      modification, and vacuolar traffic, are overrepresented. Our results greatly
      enlarge the number of known genes that affect telomere metabolism and will
      provide insights into how telomere function is linked to many other cellular
      processes.

PMID- 15161974
TI  - Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis
      patients failing to respond to interferon beta.
AB  - Identifying effective treatment combinations for MS patients failing standard
      therapy is an important goal. We report the results of a phase II open label
      baseline-to-treatment trial of a humanized monoclonal antibody against CD25
      (daclizumab) in 10 multiple sclerosis patients with incomplete response to IFN
      beta therapy and high brain inflammatory and clinical disease activity.
      Daclizumab was very well tolerated and led to a 78% reduction in new contrast
      enhancing lesions and to a significant improvement in several clinical outcome
      measures.

PMID- 15161975
TI  - Structural characterization of the fusion-active complex of severe acute
      respiratory syndrome (SARS) coronavirus.
AB  - The causative agent of a recent outbreak of an atypical pneumonia, known as
      severe acute respiratory syndrome (SARS), has been identified as a coronavirus
      (CoV) not belonging to any of the previously identified groups. Fusion of
      coronaviruses with the host cell is mediated by the envelope spike protein. Two
      regions within the spike protein of SARS-CoV have been identified, showing a high
      degree of sequence conservation with the other CoV, which are characterized by
      the presence of heptad repeats (HR1 and HR2). By using synthetic and recombinant
      peptides corresponding to the HR1 and HR2 regions, we were able to characterize
      the fusion-active complex formed by this novel CoV by CD, native PAGE,
      proteolysis protection analysis, and size-exclusion chromatography. HR1 and HR2
      of SARS-CoV associate into an antiparallel six-helix bundle, with structural
      features typical of the other known class I fusion proteins. We have also mapped
      the specific boundaries of the region, within the longer HR1 domain, making
      contact with the shorter HR2 domain. Notably, the inner HR1 coiled coil is a
      stable alpha-helical domain even in the absence of interaction with the HR2
      region. Inhibitors binding to HR regions of fusion proteins have been shown to be
      efficacious against many viruses, notably HIV. Our results may help in the design
      of anti-SARS therapeutics.

PMID- 15161976
TI  - Microtubule-stabilizing agents based on designed laulimalide analogues.
AB  - Laulimalide is a potent, structurally unique microtubule-stabilizing agent
      originally isolated from the marine sponge Cacospongia mycofijiensis. Laulimalide
      exhibits an activity profile different from other microtubule-binding agents,
      notably including effectiveness against paclitaxel-resistant cells, but it is
      intrinsically unstable. Five analogues of laulimalide were designed to exhibit
      enhanced chemical stability yet retain its exceptional biological activities.
      Evaluations of these analogues showed that all are effective inhibitors of cancer
      cell proliferation yet differ substantially in potency with an IC(50) range of
      0.12-16.5 microM. Although all of the analogues initiated cellular changes
      similar to laulimalide, including increased density of interphase microtubules,
      aberrant mitotic spindles, and ultimately apoptosis, differences among the
      analogues were apparent. The two most potent analogues, C(16)-C(17)-des-epoxy
      laulimalide and C(20)-methoxy laulimalide, appear to have a mechanism of action
      identical to laulimalide. The C(16)-C(17)-des-epoxy, C(20)-methoxy laulimalide
      derivative, which incorporates both chemical changes of the most potent
      analogues, was significantly less potent and initiated the formation of unique
      interphase microtubules unlike the parent compound and other analogues. Two C(2)
      C(3)-alkynoate derivatives had lower potency, and they initiated abnormal
      microtubule structures but did not cause micronucleation or extensive G(2)/M
      accumulation. Significantly, paclitaxel- and epothilone-resistant cell lines were
      less resistant to the laulimalide analogues. In summary, analogues of laulimalide
      designed to minimize or eliminate its intrinsic instability have been
      synthesized, and some have been found to retain the unique biological activities
      of laulimalide.

PMID- 15161977
TI  - Molecular imaging of gene expression in living subjects by spliceosome-mediated
      RNA trans-splicing.
AB  - Spliceosome-mediated RNA trans-splicing (SMaRT) provides an effective means to
      reprogram mRNAs and the proteins they encode. SMaRT technology has a broad range
      of applications, including RNA repair and molecular imaging, each governed by the
      nature of the sequences delivered by the pre-trans-splicing molecule. Here, we
      show the ability of SMaRT to optically image the expression of an exogenous gene
      at the level of pre-mRNA splicing in cells and living animals. Because of the
      modular design of pre-trans-splicing molecules, there is great potential to
      employ SMaRT to image the expression of any arbitrary gene of interest in living
      subjects. In this report, we describe a model system that demonstrates the
      feasibility of imaging gene expression by transsplicing in small animals. This
      represents a previously undescribed approach to molecular imaging of mRNA levels
      in living subjects.

PMID- 15161978
TI  - Neurotrophins regulate Schwann cell migration by activating divergent signaling
      pathways dependent on Rho GTPases.
AB  - Neurotrophins are recognized widely as essential factors in the developing
      nervous system. Previously, we demonstrated that neurotrophin 3 activation of
      TrkC inhibits Schwann cell myelination and enhances the migration of primary
      Schwann cells through the signaling pathway regulated by the Rho GTPases Rac1 and
      Cdc42. Here, we show that neurotrophins activate divergent signaling pathways to
      promote or inhibit Schwann cell migration. Endogenous brain-derived neurotrophic
      factor acting through p75(NTR) inhibits Schwann cell migration dramatically by
      Src kinase-dependent activation of the guanine-nucleotide exchange factor Vav2
      and RhoA. Together, these results suggest that neurotrophins and their receptors
      differentially regulate Schwann cell migration through the signaling pathways
      that depend on Rho GTPases.

PMID- 15161980
TI  - Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger proteins,
      and nuclear pore complex proteins: a proteomic analysis.
AB  - SUMO, a small ubiquitin-related modifier, is known to covalently attach to a
      number of nuclear regulatory proteins such as p53, IkappaB, promyelocytic
      leukemia protein and c-Jun. The sumoylation reaction is catalyzed by the SUMO
      protease, which exposes the C-terminal active glycine residue of the nascent
      SUMO, the heterodimeric SUMO activating enzyme, the SUMO conjugating enzyme,
      Ubc9, and SUMO protein ligases, in a manner similar to ubiquitinylation.
      Identification of SUMO-regulated proteins is hampered by the fact that many
      sumoylated proteins are present at a level below normal detection limit. This
      limitation was overcome by either in vivo overexpression of Myc-SUMO or in vitro
      sumoylation with excess biotin-SUMO and Ubc9. Sumoylated proteins so obtained
      were affinity purified or isolated by immunoprecipitation. The isolated
      sumoylated proteins were identified by sequence analysis using mass spectrometric
      methods. Results reveal that several heterogeneous nuclear ribonucleoproteins
      (hnRNPs), zinc finger proteins, and nuclear pore complex proteins were
      sumoylated. The sumoylation of hnRNP A1, hnRNP F, and hnRNP K were confirmed in
      vivo by coimmunoprecipitation. In view of the facts that hnRNPs have been
      implicated in RNA splicing, transport, stability, and translation, our findings
      suggest that sumoylation could play an important role in regulating mRNA
      metabolism.

PMID- 15161981
TI  - Musculoskeletal ultrasound--a state of the art review in rheumatology. Part 2:
      Clinical indications for musculoskeletal ultrasound in rheumatology.
AB  - Rheumatologists remain divided on whether they should introduce musculoskeletal
      ultrasound (MSUS) into their clinical practice. A central issue in the
      application of MSUS in clinical rheumatology is the need for proof of clinical
      relevance and improved patient care. There is now accumulating evidence that MSUS
      improves clinical diagnosis and intervention skills. High-resolution ultrasound
      is superior to clinical examination in the diagnosis and localization of joint
      and bursal effusion and synovitis. MSUS is the imaging modality of choice for the
      diagnosis of tendon pathology. MSUS is seven times more sensitive than plain
      radiography in the detection of rheumatoid erosions, allowing earlier diagnosis
      of progressive rheumatoid arthritis. Ligament, muscle, peripheral nerve and
      cartilage pathology can also be readily demonstrated by MSUS. There is exciting
      evidence that MSUS may potentially be used by rheumatologists to non-invasively
      diagnose and monitor not just joint and muscle disease but also nerve compression
      syndromes, scleroderma, vasculitis and Sjogren's syndrome. Joint aspiration and
      injection accuracy can be improved by MSUS, with initial evidence confirming
      improved efficacy. As the number of rheumatologists performing MSUS increases and
      the technical capabilities of MSUS improve, there is likely to be a growing
      number of proven clinical indications for the application of MSUS in rheumatology
      practice. This paper reviews the evidence for the application of MSUS in
      rheumatology.

PMID- 15161979
TI  - Differences in signaling pathways by IL-1beta and IL-18.
AB  - IL-1 and IL-18 are members of the IL-1 family of ligands, and their receptors are
      members of the IL-1 receptor family. Although several biological properties
      overlap for these cytokines, differences exist. IL-18 uniquely induces IFN-gamma
      from T lymphocytes and natural killer cells but does not cause fever, whereas
      fever is a prominent characteristic of IL-1 in humans and animals. In the present
      study, human epithelial cells were stably transfected with the IL-18 receptor
      beta chain and responded to IL-18 with increased production of IL-1alpha, IL-6,
      and IL-8. Five minutes after exposure to either cytokine, phosphorylation of
      mitogen activated protein kinase (MAPK) p38 was present; specific inhibition of
      p38 MAPK reduced IL-18 activity to background levels. Whereas IL-1beta induced
      the expression of the NF-kappaB-reporter gene and was suppressed by competitive
      inhibition of NF-kappaB binding, IL-18 responses were weak or absent. In contrast
      to IL-1beta, IL-18 also did not activate degradation of the NF-kappaB inhibitor.
      After 4 h, both cytokines induced comparable levels of mRNA for the chemokine IL
      8 but, in the same cells, steady-state levels of cyclooxygenase (COX)-2 mRNA were
      high after IL-1beta but low or absent after IL-18. After 30 h, IL-18-induced COX
      2 appeared in part to be IL-1 dependent. Similarly, low levels of prostaglandin
      E2 were measured in IL-18-stimulated A549 cells and freshly obtained primary
      human monocytes and mouse macrophages. We conclude that in epithelial cells, IL
      18 signal transduction is primarily via the MAPK p38 pathway rather than NF
      kappaB, which may explain the absence of COX-2 and the failure of IL-18 to cause
      fever.

PMID- 15161982
TI  - Oral health is impaired in Behcet's disease and is associated with disease
      severity.
AB  - OBJECTIVES: This study aimed to investigate the oral health of Turkish patients
      with Behcet's disease (BD) and whether it is associated with the disease course.
      METHODS: One hundred and twenty patients with BD, 35 patients with recurrent
      aphthous stomatitis (RAS) and 65 healthy Turkish controls (HC) were included in
      the study. Oral health was investigated by indices applied in a BD out-patient
      clinic. RESULTS: The mean scores of plaque, sulcus bleeding and gingival indices,
      probing depth and the number of extracted teeth were observed to be higher in
      patients with BD and RAS compared to HC (P<0.05). In the linear regression
      analysis, plaque index score was associated with the presence of oral ulcers and
      male gender. An elevated plaque index score was observed to be a significant risk
      factor for increased severity score in patients with BD in the logistic
      regression analysis (P = 0.034). CONCLUSIONS: Oral health is impaired in BD and
      associated with disease severity. Improvement of the oral health of BD patients
      may affect their disease course, leading to a better prognosis.

PMID- 15161983
TI  - Analysis of the relationship between disease activity and damage in patients with
      systemic lupus erythematosus--a 5-yr prospective study.
AB  - OBJECTIVE: To determine whether initial damage, disease duration, age, initial
      health status, average disease activity over the 5 yr or an average medication
      score covering the follow-up period would predict an increase in damage in
      patients with systemic lupus erythematosus (SLE) within the next 5 yr. METHODS: A
      5-yr prospective longitudinal study of a cohort of 141 consecutive patients with
      SLE attending a specialist lupus out-patient clinic in London from their first
      assessment between July 1994 and February 1995. Disease activity was assessed
      using the BILAG system, initial health status by the Medical Outcome Survey Short
      Form 20 with an extra question about fatigue (SF-20+) and damage by the SLICC/ACR
      Damage Index (SDI). Damage was reassessed 5 yr later. Statistical analysis was
      carried out using multiple logistic regression analysis (logXact). RESULTS: One
      hundred and thirty-three female and eight male SLE patients (97 Caucasians, 16
      Afro-Caribbeans, 22 Asians and 6 others) were included, their age at inclusion
      was 41.1 +/- 12.5 yr and their disease duration 10.2 +/- 6.3 yr. The mean
      measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7) and
      medication score 1.2 (0-3). Six patients were lost to follow-up because they had
      moved. Of the remaining 135 patients total damage had increased in 40 patients
      and 10 patients had died. At the end of the study, at 4.63 +/- 0.19 yr, the total
      SDI had increased to 1.6 +/- 1.7. Multiple logistic regression analysis revealed
      that death and increase in damage were strongly predicted by a high total disease
      activity over the entire study period (P<0.001) as we had hypothesized. When the
      total BILAG score was replaced by the average number of A-flares the prediction
      of accrual of damage during the study period was again highly significant (P =
      0.004). CONCLUSIONS: In this first prospective study of its type a highly
      significant impact of total disease activity, as measured over 5 yr using the
      BILAG system, on the development of total damage was revealed. Moreover, these
      results provide further proof of the validity of the SDI and support the BILAG
      concept of the A-flares.

PMID- 15161984
TI  - Microtubule stabilization in the treatment of solid tumors: role of the taxanes.

PMID- 15161985
TI  - Preclinical pharmacology of the taxanes: implications of the differences.
AB  - Taxanes are one of the most powerful classes of compounds among all
      chemotherapeutic drugs. Only 30 years separate the isolation of the first taxane
      from the results of direct clinical comparisons in metastatic breast, ovarian,
      and lung cancer between the two taxanes available in routine clinical practice.
      These results suggest a more favorable benefit-to-risk ratio for docetaxel
      compared to paclitaxel when these drugs are used as single agents or in
      combination with other chemotherapeutic agents in an every-3-week dosing regimen.
      Pharmacological data support the difference between the taxanes, likely
      explaining the clinical results. Considering the molecular pharmacology of the
      two drugs, docetaxel appears to bind to beta-tubulin with greater affinity and
      has a wider cell cycle activity than paclitaxel. Docetaxel also appears to have
      direct antitumoral activity via an apoptotic effect mediated by bcl-2
      phosphorylation. In addition, docetaxel has a longer retention time in tumor
      cells than paclitaxel because of greater uptake and slower efflux.
      Pharmacokinetics and pharmacodynamics of the taxanes show both agents to be
      extensively metabolized in the liver, and paclitaxel has a nonlinear
      pharmacokinetic behavior while docetaxel has linear pharmacokinetics. These
      differences explain the more simple treatment schedule and favorable results for
      docetaxel as a single agent and in combination therapy. Last, but not least,
      there is a pharmacokinetic interaction between paclitaxel and the anthracyclines,
      an active class of compounds commonly used in the treatment of breast cancer.
      This pharmacokinetic interaction is associated with greater cardio- and
      myelotoxicities, which are sequence dependent. These pharmacological data likely
      explain the different clinical development strategies for the two molecules as
      well as the different clinical results from individual trials and direct
      comparisons.

PMID- 15161986
TI  - The treatment of advanced gastric cancer: new findings on the activity of the
      taxanes.
AB  - Globally, gastric cancer is one of the most common types of cancer and one of the
      most frequent causes of cancer-related death. Despite many advances in the
      diagnosis and treatment of this disease, the prognosis for gastric cancer remains
      poor, especially in more advanced stages. In metastatic disease, benefits in
      survival and quality of life have been demonstrated in patients with unresectable
      or metastatic gastric cancer receiving chemotherapy plus best supportive care
      versus best supportive care alone. The taxanes, which are among the most
      promising cytotoxic agents in clinical use, have shown encouraging activity in
      early-phase studies as single agents and in combination regimens in the treatment
      of advanced gastric cancer. Recently, interim results of a randomized phase III
      trial comparing the triplet of docetaxel, cisplatin, and 5-fluorouracil with a
      standard reference regimen of cisplatin and 5-fluorouracil were reported.
      Patients treated with the docetaxel-containing regimen had a statistically
      superior response rate and time to disease progression as well as a clinically
      significant prolongation of survival. This study underscores the importance of
      developing new therapeutic options for patients with advanced gastric cancer.

PMID- 15161987
TI  - Taxane-platinum combinations in advanced non-small cell lung cancer: a review.
AB  - Platinum-based chemotherapy is the treatment of choice for patients with non
      small cell lung cancer (NSCLC). As a result of their single-agent activities and
      synergistic effects, taxane-platinum combinations are often used as first-line
      therapy for this disease. Four large, multicenter, randomized phase III clinical
      trials (the TAX 326 trial, the Southwest Oncology Group 9509 trial, the Italian
      Lung Cancer Project, and the Eastern Cooperative Oncology Group 1594 trial) have
      compared taxane-platinum combinations (docetaxel and paclitaxel) with other
      platinum combinations (vinorelbine and gemcitabine) in chemotherapy-naive
      patients with good performance status scores and advanced disease. The end points
      for these large randomized clinical trials were survival, response rate, adverse
      events, and quality of life (QOL). Of the taxane-platinum combinations tested,
      docetaxel-cisplatin was the only platinum combination to yield survival and
      response rates superior to another platinum combination. In adverse event terms,
      the taxane-platinum combination of paclitaxel-carboplatin demonstrated less grade
      3 or 4 neutropenia and lower rates of febrile neutropenia than other taxane
      platinum combinations but higher rates of irreversible grade 3 or 4 peripheral
      neuropathy than any of the other taxane-platinum combinations. Additional
      differences emerged when QOL data were evaluated. The docetaxel-platinum
      combination demonstrated broad QOL benefits for patients receiving this
      combination, and this benefit was not observed with the other platinum or taxane
      platinum combinations. As our use of these taxane-platinum combinations expands,
      these differences in survival, response rate, adverse events, and QOL will permit
      us to better balance our treatment goals for all patients with all stages of
      NSCLC.

PMID- 15161989
TI  - Teaching resources. Chloride concentration and pH along the endosomal pathway.
AB  - This animation depicts three membrane trafficking routes in a mammalian
      neurosecretory cell, highlighting the changing Cl- concentrations and pH values
      of the various endosomal subcompartments. The focus is on the endocytotic pathway
      and the different paths taken by clathrin-coated vesicles: the pathway for
      receptor recycling to the plasma membrane, the lysosomal pathway, or the pathway
      for synaptic vesicle recycling (in neurons). Each compartment shown has a
      distinctive pH and [Cl-], with values for pH indicated in blue and values for Cl-
      indicated in orange. This animation will be useful for teaching cell biology and
      highlighting both the dynamic nature of vesicular traffic and the changes in
      ionic balance associated with different cellular compartments.

PMID- 15161988
TI  - Docetaxel and paclitaxel in the treatment of breast cancer: a review of clinical
      experience.
AB  - In the 10 years since their initial licensing in Europe, the taxanes, paclitaxel
      and docetaxel, have emerged as fundamental drugs in the treatment of breast
      cancer. Clinically meaningful benefits were first shown in the metastatic
      setting, and large-scale exploration of their roles in the adjuvant therapy of
      early-stage disease is ongoing. Benefits have been seen in the neoadjuvant
      setting as well, mainly with docetaxel. This paper reviews the current roles of
      the taxanes in the treatment of metastatic and early-stage breast cancer. Also
      addressed are outstanding issues involving optimal dosing and sequencing, as well
      as a discussion of the relative merits of each agent in this setting. Clinicians
      should choose a taxane-based regimen for their patients with breast cancer based
      on consideration of the pharmacokinetics, clinical activity, and dosing schedule
      that best meets the patients' needs. At the current time, the pharmacokinetic
      profile, consistent positive clinical results, and convenience of an
      intermittent, short-infusion schedule have made docetaxel the preferred taxane
      for many clinicians treating patients with breast cancer.

PMID- 15161990
TI  - Teaching resources. Spatial and temporal dynamics of signaling components
      involved in the control of chemotaxis in Dictyostelium discoideum.
AB  - This animation shows the redistribution of several proteins during the
      chemotactic response of the single-celled organism Dictyostelium discoideum to
      the chemoattractant cAMP. Much like neutrophils, this organism is able to sense
      and move toward very shallow gradients of chemoattractant. Mutant strains
      carrying mutations in genes encoding various signaling components are available
      and, thus, D. discoideum serves as a model organism for the study of the cellular
      mechanisms that control chemotaxis and amplification of a signaling gradient
      across a single cell. The animation would be useful in depicting the dynamic
      nature of signal transduction, the ability of cells to polarize to allow for
      directional movement, and the spatial and temporal changes in the activity of
      specific proteins that accompany chemotactic responses.

PMID- 15161991
TI  - Teaching resources. Regulation of GABA receptor activity by neurosteroids and
      phosphorylation.
AB  - These two animations show two models for how neurosteroids regulate the flow of
      chloride ions (Cl(-)) through ionotropic gamma-aminobutyric acid (GABA)
      receptors. In the first model, binding of the neurosteroid allows a protein
      kinase C (PKC) phosphorylation site to become accessible. Phosphorylation of the
      channel increases flux through the channel. In the second model, phosphorylation
      by PKC allows the neurosteroid to bind and increase flux through the channel. The
      animations have two parts: (i) a diagrammatic representation of the sequence of
      events at the channel in the membrane and (ii) a representative current trace of
      data obtained using electrophysiological techniques. These animations would be
      useful in teaching how allosteric modulators (neurosteroids) and covalent
      modulators (kinases) can work together as regulators of protein activity.

PMID- 15161992
TI  - Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary
      mechanics in preterm infants.
AB  - The changes induced on respiratory mechanics and on tracheobronchial aspirate
      fluid (TAF) cytology by dexamethasone courses started at two different postnatal
      ages in preterm infants at risk of chronic lung disease (CLD) were reported in
      this clinical trial designed in two phases. The first phase of the study included
      20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks,
      who were oxygen and ventilator dependent on the 10th day of life. They were
      randomly assigned to the moderately early dexamethasone (MED) group or to the
      control group. The second phase of the study included 20 neonates with the same
      characteristics, oxygen and ventilator dependent on the 4th day of life, randomly
      assigned to the early dexamethasone (ED) group or to the control group. Both
      treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for
      the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the
      last day of treatment). The control groups received no steroid treatment. A
      significantly lower absolute cell count and percentage of neutrophils (PMN) in
      the TAF and significantly higher dynamic lung compliance (Cdyn) values were
      observed in both the MED treated compared to the untreated infants and the ED
      treated infants compared to the control group. Moreover these changes were more
      precocious in the ED Group compared to the MED Group. Our study suggests that
      dexamethasone could be more efficacious in reducing effects of ventilator-induced
      lung injury in preterm infants at high risk of CLD when started earlier.

PMID- 15161993
TI  - Inhibitory effects of metabolite I of erdosteine on the generation of nitric
      oxide and peroxynitrite chemiluminescence by human neutrophils.
AB  - Polymorphonuclear neutrophils (PMNs) can generate superoxide anions and nitric
      oxide (NO), which is not only an important mediator of various cellular
      activities, but can also react with superoxide anions to produce peroxynitrite
      anions (ONOO-). Peroxynitrite is a potent and potentially toxic oxidant that
      damages various types of biomolecules. It preferentially mediates the oxidation
      of thiolic groups in protein and non-protein molecules, thus altering their
      functions. The aim of this study was to examine whether, in addition to its
      ability to reduce the respiratory bursts of human PMNs, the SH metabolite I (Met
      I) of erdosteine, can interfere with NO and NO-derived peroxynitrite production,
      thus extending its antioxidant activity. This was done by means of the luminol
      amplified chemiluminescence (LACL), which has been widely used to detect the
      production of reactive oxidant species (ROS) by PMNs under various conditions. At
      5 and 10 microg/ml, Met I significantly reduced LACL after fMLP and PMA
      stimulation. When L-Arg was added to the reaction medium, as a NO donor, the
      chemiluminescence of fMLP increased by up to 67% and that of PMA by up to 132%,
      but was once again significantly reduced by 5 and 10 microg/ml of Met I. In a
      cell-free system, the use of linsidomine (SIN-1) makes it possible to investigate
      the behavior of LACL induced by peroxynitrite release, which was significantly
      reduced by Met I concentrations ranging from 1.25 to 10 microg/ml. Our findings
      indicate that Met I, a molecule with a SH group, reacts with ROS, NO and NO
      derived peroxynitrite, and has both antioxidant and scavenging activity. This is
      of interest for the strategy of protecting against damage induced by radical
      species in the pulmonary cell environment, in which they can induce a phlogogenic
      loop, and suggests that adding exogenous thiols may be useful in antagonizing the
      toxic effects of reactive molecules on endogenous thiols.

PMID- 15161994
TI  - Effects of melatonin on impaired neurogenic and endothelial relaxations by
      bacterial lipopolysaccharide in the mouse corpus cavernosum.
AB  - We investigated whether bacterial lipopolysaccharide treatment causes any
      neuronal and vascular hyporeactivity in mouse cavernous tissue and also whether
      melatonin has any restorative effect on this possible neuronal and vascular
      hyporesponsiveness. Lipopolysaccharide treatment attenuated contractions in
      response to phenylephrine. Treatment with the inducible nitric oxide synthase
      inhibitor aminoguanidine or melatonin restored the hypocontractility of the
      cavernous smooth muscle to phenylephrine. Relaxant responses of corpus cavernosum
      precontracted by phenylephrine to acetylcholine or electrical field stimulation
      were significantly impaired in mice treated with bacterial lipopolysaccharide.
      Treatment with aminoguanidine or melatonin could prevent the impairment of the
      neuronal and endothelial relaxations. There was no significant difference between
      control and lipopolysaccharide-treated groups in the contractile response to high
      dose KCl and in the relaxant response to papaverine. In conclusion, bacterial
      lipopolysaccharide treatment caused a neuronal and endothelial dysfunction in the
      mouse corpus cavernosum. A possible increased oxidative activity in the cavernous
      tissue may be a major reason for the impairment of relaxant responses and
      hypocontracility of tissue. The restorative effects of melatonin on this
      hyporeactivity may depend on its antioxidant properties and partly on its
      inhibitory action on the inducible nitric oxide synthase production.

PMID- 15161995
TI  - Effect of COX-1/COX-2 inhibition versus selective COX-2 inhibition on coronary
      vasodilator responses to arachidonic acid and acetylcholine.
AB  - The effect of a nonselective COX-1/COX-2 inhibitor, naproxen, was compared with a
      COX-2-selective inhibitor (SC-58236) on coronary vasodilatory responses in the
      anesthetized dog. Coronary vasodilation was induced by direct intracoronary
      injection of acetylcholine (ACH) and arachidonic acid (AA) in control animals and
      in those treated with either naproxen (1, 3, or 10 mg/kg p.o. 24 h prior to the
      experiment) or SC-58236 (1, 5, or 15 mg/kg p.o. 24 h prior to the experiment).
      Naproxen, at 10 mg/kg, significantly attenuated the AA-induced vasodilation
      (prostacyclin dependent) with no effect on ACH-induced vasodilation (nitric oxide
      dependent). SC-58236 failed to attenuate either AA- or ACH-induced vasodilation.
      Ex vivo assays were utilized to establish inhibition of COX-2 (lipopolysaccharide
      stimulated prostaglandin E2 formation) and COX-1 (serum thromboxane B2) in blood
      taken from dogs administered 1, 3, or 10 mg/kg naproxen or 15 mg/kg SC-58236.
      Naproxen (3 and 10 mg/kg) and SC-58236 (15 mg/kg) markedly reduced the
      lipopolysaccharide-induced prostaglandin E2 formation, whereas SC- 58236 (15
      mg/kg) had no effect on serum thromboxane B2. Naproxen significantly reduced
      thromboxane B2 at all three doses studied. Furthermore, naproxen (10 mg/kg p.o.)
      significantly inhibited the AA-induced platelet aggregation (thromboxane B2
      dependent), whereas SC-58236 had no effect. Collectively, these results
      demonstrate that SC-58236 is selective for COX-2, while naproxen is a
      nonselective inhibitor. These data also suggest that vasodilatory responses to AA
      in the dog are primarily COX-1 dependent. Selective COX-2 inhibition does not
      affect either prostacyclin or nitric oxide mediated vasodilation in the canine
      coronary circulation.

PMID- 15161996
TI  - Antitussive profile of the NOP agonist Ro-64-6198 in the guinea pig.
AB  - We have previously shown that N/OFQ, the endogenous peptide ligand for the
      'opioid-like' NOP receptor, inhibits cough in guinea pigs and cats. In the
      present study we sought to continue our characterization of the cough-suppressant
      effects of NOP stimulation by profiling the pulmonary and antitussive effects of
      a novel non-peptide NOP agonist, Ro-64-6198, in guinea pigs. In receptor-binding
      assays, we confirmed that Ro-64-6198 selectively binds to NOP receptors over
      other opioid receptors. The Ki values for Ro-64-6198 at NOP, MOP, KOP and DOP
      receptors was 0.3, 36, 214 and 3,787 nmol/l, respectively. In GTPgammaS-binding
      assays, Ro-64-6198 displayed >900-fold functional selectivity at NOP relative to
      MOP receptors. We evaluated the effects of Ro-64-6198 (3 and 10 micromol/l) in
      isolated guinea pig nodose ganglia cells on the increases in intracellular Ca2+
      concentration evoked by capsaicin stimulation (1 x 10(-8)-1 x 10(-6) mol/l).
      Similar to previously reported data with N/OFQ, Ro-64-6198 (3 and 10 micromol/l)
      significantly attenuated Ca2+ responses in nodose ganglia cells produced by
      exposure to capsaicin. The effect of Ro-64-6198 (3 micromol/l) on capsaicin
      induced intracellular Ca2+ responses was blocked by the NOP antagonist, J113397
      (3 micromol/l). In guinea pig in vivo studies, aerosolized capsaicin (10-300
      micromol/l) produced a dose-dependent increase in cough number. Ro-64-6198 given
      i.p. significantly inhibited cough due to capsaicin (300 micromol/l) exposure. In
      a duration study we found that the maximum antitussive effect (42 +/- 8%
      inhibition) of Ro-64-6198 (3 mg/kg) was observed at 1 h after i.p.
      administration. Also at 1 h after administration, Ro-64-6198 (0.003-3.0 mg/kg,
      i.p.) produced a dose-dependent inhibition of cough. The antitussive effect of Ro
      64-6198 (3 mg/kg, i.p.) was blocked by J113397 (12 mg/kg, i.p.) but not by the
      classical opioid antagonist naltrexone (10 mg/kg, i.p.). Although the antitussive
      action of Ro-64-6198 may be mediated by a central and/or a peripheral site of
      action, we hypothesize that selective oral NOP agonists that do not penetrate the
      blood-brain barrier may provide a novel approach for the treatment of cough.
      Moreover, because these drugs do not interact at MOP receptors, they may be
      devoid of codeine-like side effects such as respiratory depression, sedation,
      constipation or proclivities for addictive liabilities.

PMID- 15161997
TI  - Transdermal eperisone elicits more potent and longer-lasting muscle relaxation
      than oral eperisone.
AB  - Eperisone hydrochloride is widely used for the treatment of plasticity to relieve
      muscle stiffness and back pain. However, oral eperisone has a very low
      bioavailability and short muscle relaxant activity, because of the profound
      intestinal first-pass metabolism. To improve the efficacy and compliance of
      eperisone, we designed a new dosage form, a transdermal patch, and evaluated the
      efficacy of the eperisone patch with the muscle relaxant activity of rats. The
      muscle relaxant activity was assessed by the measurement of forelimb grip
      strength and hanging test in rats. The transdermal patch of eperisone showed
      significantly enhanced muscle relaxant activity at 0.5 1.5 and 3 cm2/200 g rat
      (1.39, 4.17 and 8.33 mg of eperisone hydrochloride/kg, respectively) in a dose
      dependent manner and the effects lasted over 24 h. Even though oral eperisone
      hydrochloride showed significant muscle relaxant activity at 12.5, 25 and 50
      mg/kg in a dose-dependent manner, the activity lasted only 1 or 2 h after
      administration. These results suggest that eperisone as transdermal patch form
      showed efficient absorption with more potent and longer-lasting muscle relaxant
      activity than oral solution. The transdermal patch form of eperisone will
      increase the efficacy and compliance in the clinical use of eperisone.

PMID- 15161998
TI  - Comparative effects of quinapril with enalapril in rats with heart failure.
AB  - The cardioprotective properties of angiotensin-converting enzyme (ACE)
      inhibitors, quinapril and enalapril were studied in a rat model of heart failure.
      Seventy-five rats were divided into five groups and administered quinapril or
      enalapril at 2 and 20 mg/kg/day (groups Q2, Q20, E2 and E20) or vehicle alone
      (group V, all groups n = 15). Although both ACE inhibitors improved survival rate
      and ventricular function in a dose-dependent manner, the left ventricular end
      diastolic pressure and expression level of transforming growth factor-beta1 mRNA
      were the lowest in group Q20. These results suggest that quinapril may confer
      greater protection than enalapril against injury from the renin-angiotensin
      system in heart failure.

PMID- 15161999
TI  - Cabergoline stimulates synthesis and secretion of nerve growth factor, brain
      derived neurotrophic factor and glial cell line-derived neurotrophic factor by
      mouse astrocytes in primary culture.
AB  - Neuroprotection is the primary concern in patients with newly diagnosed
      Parkinson's disease. The D2/weak D1 dopamine agonist cabergoline elicits
      neuroprotection by antioxidation and scavenging free radicals, and may protect
      neurons by up-regulating endogenous neurotrophic factors synthesis in the brain.
      In primary cultured mouse astrocytes, cabergoline 37 micromol/l immediately
      elevated concentrations of nerve growth factor, brain-derived neurotrophic
      factor, and glial cell line-derived neurotrophic factor (GDNF) in culture medium,
      reaching 9.9-, 2.6- and 30-fold, respectively, of control levels at 16 h.
      Relative mRNA levels were 3.0-, 1.5- and 1.9-fold, respectively, of controls at 3
      h. These effects may be mediated partly by the dopamine D2 receptor. Cabergoline
      may be a good candidate for an inducer of GDNF, which may have neuroprotective
      and neurorestorative properties in dopaminergic nigral neurons.

PMID- 15162000
TI  - The importance of distinguishing between sublevel IA and IB in neck dissection.

PMID- 15162001
TI  - The quantification of endolymphatic hydrops in an experimental animal model with
      guinea pigs.
AB  - To better quantify endolymphatic hydrops in experimental guinea pigs,
      endolymphatic hydrops was induced by endolymphatic sac obliteration through an
      extradural posterior cranial fossa approach in the right ear. The area of the
      scala vestibuli and scala media of each turn on both cochlear midmodiolar
      sections was measured, using an automated computer-aided design (AutoCAD R14)
      software combined with a digital camera. No endolymphatic hydrops was observed in
      all nonoperated ears; however, various degrees of hydrops were present in all
      operated ears. The average maximum SMA (scala media area) ratio in the 4-week
      group (2.22 +/- 0.20) was greater than that in the control group (1.10 +/- 0.06).
      The average maximum SMA ratio of the 8-week group (4.04 +/- 0.52) was greater
      than that of the 4-week group (p < 0.05). This study provides a reliable
      methodologic base for the experimental study of Meniere's disease.

PMID- 15162002
TI  - Rapidly prototyped temporal bone model for otological education.
AB  - The anatomy of the temporal bone is extremely complicated. If a three-dimensional
      model could be simulated, it would greatly contribute to the stereoscopic
      understanding of anatomy and surgery. A simulated three-dimensional model of a
      human temporal bone was prototyped using the selective laser sintering method.
      The model could be shaved using a surgical drill in the same way as in real
      surgery. A magnified model was particularly useful for the instruction of anatomy
      and surgery. When a translucent area was selected, a bony labyrinth could be
      created together with an internal auditory meatus and facial nerve, which also
      contributed to the easy understanding of the inner ear structure. The three
      dimensional prototyped model using selective laser sintering serves as a good
      educational material for middle ear anatomy and surgery.

PMID- 15162003
TI  - Cyclo-oxygenase 2 expression in laryngeal squamous cell carcinoma and its
      clinical correlates.
AB  - OBJECTIVE: To assess the significance of cyclo-oxygenase 2 (COX-2) in laryngeal
      squamous cell carcinoma (LSCC). STUDY DESIGN: An immunohistochemical study in
      which 39 patients with LSCC were included. METHODS: Immunohistochemical staining
      of the paraffin-embedded tumour tissues was performed using isoform-specific COX
      2 polyclonal antisera (Santa Cruz, Calif., USA). COX-2 results were compared with
      the clinical parameters of the patients. RESULTS: COX-2 was detected in all
      tumour tissues. In the normal laryngeal tissue around the tumour area, which
      served as control, there was no COX-2 staining. There was no relationship between
      the COX-2 results and the location of the primary tumour, T stage and N stage,
      survival, recurrence or pulmonary metastases. CONCLUSION: The absence of a
      relation between COX-2 positivity and clinical parameters may suggest an
      involvement of COX-2 in laryngeal carcinogenesis. Since COX-2 positivity could be
      detected in all LSCC specimens studied, COX-2 could serve as a therapeutic target
      in LSCC.

PMID- 15162004
TI  - Acoustic and perceptual parameters relating to connected speech are more reliable
      measures of hoarseness than parameters relating to sustained vowels.
AB  - This report investigates the correlations between acoustic parameters and the
      perception of hoarseness by trained listeners. Both sustained vowels and
      connected speech were examined. Fourteen acoustic parameters from samples of
      sustained vowels and 2 from connected speech were measured. The results show that
      jitter, shimmer and cepstral peak prominence (CPP) are correlated with the
      perception of hoarseness in sustained vowels. CPP is strongly correlated with the
      perception of hoarseness in connected speech. Some evidence is seen that
      perception of hoarseness in connected speech is more valid than the perception of
      hoarseness in sustained vowels. It is concluded that CPP for connected speech is
      a more valid objective measure of hoarseness than jitter, shimmer or CPP for
      sustained vowels and that perception of hoarseness may be most accurate in
      connected speech, rather than isolated vowels.

PMID- 15162005
TI  - Congenital malformations of the middle ear with an intact external ear: a review
      of 38 cases.
AB  - In patients with middle ear malformations, one can expect an improvement in
      hearing following ear surgery. Thus, it is crucial for the ear surgeon to have an
      increased awareness of this disease. For a better understanding of this
      condition, 38 patients who underwent ear surgery were studied. All patients had
      congenital ossicular malformations but with an intact external ear. On the basis
      of our intra-operative observations, 15 cases were assigned to group A (single
      malformation) and 23 cases to group B (multiple malformations). The pre-operative
      air-conduction threshold in group B patients was higher than that in group A. Pre
      operatively in group A 2 out of 20 ears had mild, 17 had moderate and 1 had
      severe hearing loss (HL). In group B, out of 25 ears, 3 had mild, 13 had moderate
      and 9 had severe HL. Post-operatively in group A, 2 had normal hearing, 16 had
      mild, 2 had moderate and none had severe HL. In group B, postoperatively 1 had
      normal hearing, 18 had mild, 4 moderate and 2 severe HL. Therefore, in patients
      with multiple middle ear malformations, the surgeon should know that the prospect
      of an improvement in the hearing threshold is rather low even after surgical
      reconstruction.

PMID- 15162006
TI  - Cochlear administration of adenosine triphosphate facilitates recovery from
      acoustic trauma (temporary threshold shift).
AB  - BACKGROUND: Adenosine triphosphate (ATP) has often been used in the treatment of
      acoustic trauma although evidence supporting its clinical use was lacking. The
      aim of this study was to evaluate the chronic effects of ATP on acoustic trauma
      in guinea pigs. METHODS: We infused ATP into the perilymph of the guinea pig
      cochlea concurrently with intense noise exposure to investigate the effect of ATP
      on the process of recovery after acoustic trauma. We assessed auditory brainstem
      response (ABR) thresholds to evaluate cochlear function. RESULTS: After noise
      exposure (120 dB SPL, 5 h), ABR thresholds showed an increase of approximately 50
      dB SPL that returned to normal after 14 days. Cochlear function in ATP-treated
      ears recovered more quickly than in control ears. The effect of ATP was inhibited
      by the administration of the ATP receptor antagonist: pyridoxal- phosphate-6
      azophenyl-2',4'-disulfonic acid. CONCLUSION: These results suggest that ATP
      mitigates the effects of noise trauma through the ATP receptor.

PMID- 15162007
TI  - Sinonasal malignancy: what's new?
AB  - Tumors of the nasal cavity are located at a complex anatomic site and show a huge
      histological diversity. Although dealing with a rare malignancy, the last decade
      has brought--besides new histological and clinical classifications--a variety of
      new insights into etiological agents, tumor biology and therapeutic concepts as
      well as valuable overviews of rare histological subtypes. This review tries to
      disentangle the different medical and scientific aspects of the most frequently
      encountered histological types of tumors in the nasal cavity and the paranasal
      sinuses. We concentrate on epidemiology, classification, etiology, cytogenetics
      and molecular genetics, outcome and prognosis as well as treatment modalities, as
      far as the past few years have brought considerable new insights. Our principal
      aim is to provide the clinician with important data from publications of the last
      decade.

PMID- 15162008
TI  - Ossifying haemangioma of the frontal sinus.
AB  - First described by Natali, the ossifying haemangioma is a rare entity. Although
      cases of ossifying haemangioma have been described in the literature, no
      involvement of the frontal sinus has been presented yet. We present a 46-year-old
      female patient who complained of recurrent cephalalgia and pressure in her
      forehead for 3 months. A computerized tomography scan demonstrated a compact
      radiopaque density arising from the floor of the middle cavity of her frontal
      sinus. Surgery was performed using the coronal approach. A rhomboid-shaped
      ossified tumour in the middle cavity of the frontal sinus was found with no signs
      of bleeding, partially obstructing the right sinus ostium. The small tumour was
      removed at the very base showing slight bleeding. Two weeks later, during the
      clinical follow-up, the patient did not complain of any of her previous symptoms.
      Previous studies have presented ossifying haemangioma of the temporal bone as an
      extremely aggressive entity affecting the 7th cranial nerve. In our case, the
      frontal sinus showed no signs of destruction of the adjacent tissue, and the only
      associated symptom was frontal cephalalgia. Because no critical surgical
      complications have been observed, no further changes to the surgical procedure
      appear necessary. We recommend performing a computerized tomography 6-12 months
      after surgery for follow-up to detect possible tumour regrowth.

PMID- 15162009
TI  - Pathways of DNA double-strand break repair and their impact on the prevention and
      formation of chromosomal aberrations.
AB  - DNA double-strand breaks (DSB) are considered the critical primary lesion in the
      formation of chromosomal aberrations (CA). DSB occur spontaneously during the
      cell cycle and are induced by a variety of exogenous agents such as ionising
      radiation. To combat this potentially lethal damage, two related repair pathways,
      namely homologous recombination (HR) and non-homologous DNA end joining (NHEJ),
      have evolved, both of which are well conserved from bacteria to humans. Depending
      on the pathway used, the underlying mechanisms are capable of eliminating DSB
      without alterations to the original genomic sequence (error-free) but also may
      induce small scale mutations (base pair substitutions, deletions and/or
      insertions) and gross CA (error-prone). In this paper, we review the major
      pathways of DSB-repair, the proteins involved therein and their impact on the
      prevention of CA formation and carcinogenesis.

PMID- 15162010
TI  - Mechanisms of DNA double strand break repair and chromosome aberration formation.
AB  - It is widely accepted that unrepaired or misrepaired DNA double strand breaks
      (DSBs) lead to the formation of chromosome aberrations. DSBs induced in the DNA
      of higher eukaryotes by endogenous processes or exogenous agents can in principle
      be repaired either by non-homologous endjoining (NHEJ), or homology directed
      repair (HDR). The basis on which the selection of the DSB repair pathway is made
      remains unknown but may depend on the inducing agent, or process. Evaluation of
      the relative contribution of NHEJ and HDR specifically to the repair of ionizing
      radiation (IR) induced DSBs is important for our understanding of the mechanisms
      leading to chromosome aberration formation. Here, we review recent work from our
      laboratories contributing to this line of inquiry. Analysis of DSB rejoining in
      irradiated cells using pulsed-field gel electrophoresis reveals a fast component
      operating with half times of 10-30 min. This component of DSB rejoining is
      severely compromised in cells with mutations in DNA-PKcs, Ku, DNA ligase IV, or
      XRCC4, as well as after chemical inhibition of DNA-PK, indicating that it
      reflects classical NHEJ; we termed this form of DSB rejoining D-NHEJ to signify
      its dependence on DNA-PK. Although chemical inhibition, or mutation, in any of
      these factors delays processing, cells ultimately remove the majority of DSBs
      using an alternative pathway operating with slower kinetics (half time 2-10 h).
      This alternative, slow pathway of DSB rejoining remains unaffected in mutants
      deficient in several genes of the RAD52 epistasis group, suggesting that it may
      not reflect HDR. We proposed that it reflects an alternative form of NHEJ that
      operates as a backup (B-NHEJ) to the DNA-PK-dependent (D-NHEJ) pathway.
      Biochemical studies confirm the presence in cell extracts of DNA end joining
      activities operating in the absence of DNA-PK and indicate the dominant role for
      D-NHEJ, when active. These observations in aggregate suggest that NHEJ, operating
      via two complementary pathways, B-NHEJ and D-NHEJ, is the main mechanism through
      which IR-induced DSBs are removed from the DNA of higher eukaryotes. HDR is
      considered to either act on a small fraction of IR induced DSBs, or to engage in
      the repair process at a step after the initial end joining. We propose that high
      speed D-NHEJ is an evolutionary development in higher eukaryotes orchestrated
      around the newly evolved DNA-PKcs and pre-existing factors. It achieves within a
      few minutes restoration of chromosome integrity through an optimized synapsis
      mechanism operating by a sequence of protein-protein interactions in the context
      of chromatin and the nuclear matrix. As a consequence D-NHEJ mostly joins the
      correct DNA ends and suppresses the formation of chromosome aberrations, albeit,
      without ensuring restoration of DNA sequence around the break. B-NHEJ is likely
      to be an evolutionarily older pathway with less optimized synapsis mechanisms
      that rejoins DNA ends with kinetics of several hours. The slow kinetics and
      suboptimal synapsis mechanisms of B-NHEJ allow more time for exchanges through
      the joining of incorrect ends and cause the formation of chromosome aberrations
      in wild type and D-NHEJ mutant cells.

PMID- 15162011
TI  - The role of homologous recombination repair in the formation of chromosome
      aberrations.
AB  - The repair of DNA double strand breaks by homologous recombination can occur by
      at least two pathways: a Rad51-dependent pathway that is predominantly error
      free, and a Rad51-independent pathway (single strand annealing, SSA) that is
      error prone. In theory, chromosome exchanges can result from (mis)repair by
      either pathway. Both repair pathways will involve a search for homologous
      sequence, leading to co-localization of chromatin. Genes involved in homologous
      recombination repair (HRR) have now been successfully knocked out in mice and the
      role of HRR in the formation of chromosome exchanges, particularly after ionising
      radiation, is discussed in the light of new evidence.

PMID- 15162012
TI  - Recombination repair pathway in the maintenance of chromosomal integrity against
      DNA interstrand crosslinks.
AB  - DNA interstrand crosslinks (ICL) present a major threat to cell viability and
      genome integrity. In eukaryotic cells, the ICLs have been suggested to be
      repaired by a complex process involving Xpf/Ercc1-mediated endonucleolytic
      incision and homologous recombination (HR). However, the entire feature of the
      ICL tolerating mechanism is still poorly understood. Here we studied chromosome
      aberrations (CA) and sister chromatid exchanges (SCE) by the use of the
      crosslinking agent mitomycin C (MMC), in chicken DT40 cells with the HR genes
      disrupted by targeted replacement. The disruption of the Rad54, Rad51B, Rad51C,
      Rad51D, Xrcc2 and Xrcc3 genes resulted in a dramatic reduction of spontaneous and
      MMC-induced SCEs. Interestingly, while HR-deficient cells were hypersensitive to
      cell killing by MMC, MMC-induced CAs were also suppressed in the HR-deficient
      cells except for Rad51D-, Xrcc2- and Xrcc3-deficient cells. These observations
      indicate that DNA double strand breaks (DSB) at stalled replication forks and
      those arising as repair intermediates present strong signals to cell death but
      can be tolerated by the HR repair pathway, where Rad54, Rad51B and Rad51C have an
      initiative role and repair can be completed by their paralogs Rad51D, Xrcc2 and
      Xrcc3. The impairment of the HR pathway, which otherwise leads to cell death, may
      be somewhat substituted by an alternative mechanism such as the Mre11/Rad50/Nbs1
      pathway, resulting in reduced frequencies of SCEs and CAs.

PMID- 15162013
TI  - Repair rates of R-band, G-band and C-band DNA in murine and human cultured cells.
AB  - Repair of cyclobutane pyrimidine dimers (CPDs) in cultured neonatal human
      fibroblasts and in Mus spretus x M. castaneus F1 neonatal skin fibroblasts was
      analyzed after UVC-irradiation by cleavage with T4 endonuclease V cyclopyrimidine
      dimer glycosylase, alkaline-agarose gel electrophoresis, and Southern blotting.
      The blots were sequentially probed with 32P-labeled Alu, or B2, to preferentially
      illuminate R-band DNA, by L1 to preferentially illuminate G-band DNA, and by
      satellite DNA to illuminate C-band DNA. These three different DNA populations
      showed slightly different global nucleotide excision repair rates that are in the
      order of speed, R-band DNA > G-band DNA > C-band DNA. Fibroblasts from out-bred
      neonatal mice and humans showed similar band-specific repair rate ratios and the
      global repair rate of murine fibroblasts was almost as rapid as that of the human
      fibroblasts. The mass distribution of the human Alu-probed signal was further
      analyzed. Gel mobility data was fitted to a logistic equation to include all M(r)
      values. Hypothetical distributions of DNA randomly cleaved to a particular number
      average molecular weight were fit to the logistic gel mobility function to
      determine how such a randomly cleaved distribution of a particular cleavage
      frequency would be displayed along the experimental gel. This revealed a rapidly
      repaired kinetic fraction that represented 17% of the Alu-probed signal (R-band
      DNA), almost none of the L1 probed signal (G-band DNA), and reflects
      transcription coupled repair of active genes. The remaining Alu-probed DNA showed
      a random distribution of UVC-induced CPDs throughout all stages of global
      nucleotide excision repair. The Alu-probed CPDs disappeared with an excellent fit
      to first order kinetics and with a half-life of seven hours.

PMID- 15162014
TI  - On the nature of visible chromosomal gaps and breaks.
AB  - From the earliest days of chromosomal aberration studies, the distinction, nature
      and origin of light-microscope observed "gaps" and "breaks" have been topics for
      debate and controversy. In this paper we survey, briefly, the various ideas that
      have appeared in the very extensive literature, and attempt to evaluate them in
      the light of our current understanding of chromosome structure and aberration
      formation. Attention is drawn to the problems of interpretation caused by G2/S
      cell imprecision.

PMID- 15162015
TI  - Molecular targets and mechanisms in formation of chromosomal aberrations:
      contributions of Soviet scientists.
AB  - Studies of mechanisms for formation of chromosomal aberrations (CAs) with special
      emphasis on data from Soviet/Russian investigations are reviewed that argue in
      favor of a minor fraction of genomic DNA that forms specific molecular
      targets/contacts for the formation of chromosomal exchanges. This DNA is
      presumably associated with matrix attachment sites of DNA loops, enriched with AT
      base pairs and repetitive DNA sequences. It is assumed that there are two main
      mechanisms in formation of chromosome aberrations: 1) mutually reciprocal
      recombination, resulting in formation of all kinds of chromosome exchanges; 2)
      the process of telomere formation, resulting in the generation of true deletions.
      A significant part of chromosomal breaks and apparently unrejoined ends in
      incomplete exchanges as seen with cytogenetic techniques reflect decondensation
      in the discrete units of chromatin organization such as the megabase-size DNA
      domains. The possible ways for further analysis of alternative theories with
      emerging technologies are also discussed.

PMID- 15162016
TI  - Progress towards understanding the nature of chromatid breakage.
AB  - The wide range of sensitivities of stimulated T-cells from different individuals
      to radiation-induced chromatid breakage indicates the involvement of several low
      penetrance genes that appear to link elevated chromatid breakage to cancer
      susceptibility. The mechanisms of chromatid breakage are not yet fully
      understood. However, evidence is accumulating that suggests chromatid breaks are
      not simply expanded DNA double-strand breaks (DSB). Three models of chromatid
      breakage are considered. The classical breakage-first and the Revell "exchange"
      models do not accord with current evidence. Therefore a derivative of Revell's
      model has been proposed whereby both spontaneous and radiation-induced chromatid
      breaks result from DSB signaling and rearrangement processes from within large
      looped chromatin domains. Examples of such rearrangements can be observed by
      harlequin staining whereby an exchange of strands occurs immediately adjacent to
      the break site. However, these interchromatid rearrangements comprise less than
      20% of the total breaks. The rest are thought to result from intrachromatid
      rearrangements, including a very small proportion involving complete excision of
      a looped domain. Work is in progress with the aim of revealing these
      rearrangements, which may involve the formation of inversions adjacent to the
      break sites. It is postulated that the disappearance of chromatid breaks with
      time results from the completion of such rearrangements, rather than from the
      rejoining of DSB. Elevated frequencies of chromatid breaks occur in irradiated
      cells with defects in both nonhomologous end-joining (NHEJ) and homologous
      recombination (HR) pathways, however there is little evidence of a correlation
      between reduced DSB rejoining and disappearance of chromatid breaks. Moreover, at
      least one treatment which abrogates the disappearance of chromatid breaks with
      time leaves DSB rejoining unaffected. The I-SceI DSB system holds considerable
      promise for the elucidation of these mechanisms, although the break frequency is
      relatively low in the cell lines so far derived. Techniques to study and improve
      such systems are under way in different cell lines. Clearly, much remains to be
      done to clarify the mechanisms involved in chromatid breakage, but the
      experimental models are becoming available with which we can begin to answer some
      of the key questions.

PMID- 15162017
TI  - Human-hamster hybrid cells used as models to investigate species-specific factors
      modulating the efficiency of repair of UV-induced DNA damage.
AB  - The human-Chinese hamster hybrid cell line XR-C1#8, containing human chromosome
      8, was used as a model system to investigate the relative importance of cellular
      enzymatic environment and chromosomal structure for modulating the efficiency of
      repair of UV-induced DNA damage. The hybrid cells were irradiated with UVC light
      and the extent of cytogenetic damage, detected as frequencies of sister chromatid
      exchanges (SCEs), was compared between the human and the hamster chromosomes. The
      combination of immunofluorescent staining for SCEs and chromosome painting with
      fluorescence in situ hybridization allowed the simultaneous analysis of SCEs in
      the human and hamster chromosomes. The aim of the present study was to determine
      if the differences in biological response to comparable UV treatments observed
      between human and hamster cells were maintained in the hybrid cells in which
      human and hamster chromosomes are exposed in the same cellular environment. The
      analysis of replication time of human chromosome 8 indicated the active status of
      this chromosome in XR-C1#8 hybrid cells. The frequencies of SCEs for human
      chromosome 8 and a hamster chromosome of comparable size were 0.35 +/- 0.52, 0.80
      +/- 0.73, 1.24 +/- 2.24 and 0.36 +/- 0.12, 0.71 +/- 0.2, 0.97 +/- 0.27,
      respectively, after irradiation with 0, 5, and 10 J/m2. The persistence of UV
      induced SCEs after three cell cycles was also analyzed, both for the human and
      hamster chromosomes. The observed frequencies of SCEs were 0.40 +/- 0.57, 0.62 +/
      1.05, 0.58 +/- 0.83 and 0.26 +/- 0.08, 0.67 +/- 0.18, 0.69 +/- 0.24, in human
      and hamster chromosomes respectively, after treatment with 0, 10, and 20 J/m2 of
      UVC light. No significant differences could be observed between the human and
      hamster chromosomes. These results suggest that the enzymatic environment of
      human and hamster cells has the main role, in comparison to the structural
      organization of human and hamster chromosomes, for determining the different
      level of repair of UV-induced DNA damage observed in these two species.

PMID- 15162018
TI  - Mechanisms and consequences of methylating agent-induced SCEs and chromosomal
      aberrations: a long road traveled and still a far way to go.
AB  - Since the milestone work of Evans and Scott, demonstrating the replication
      dependence of alkylation-induced aberrations, and Obe and Natarajan, pointing to
      the critical role of DNA double-strand breaks (DSBs) as the ultimate trigger of
      aberrations, the field has grown extensively. A notable example is the
      identification of DNA methylation lesions provoking chromosome breakage
      (clastogenic) effects, which made it possible to model clastogenic pathways
      evoked by genotoxins. Experiments with repair-deficient mutants and transgenic
      cell lines revealed both O6-methylguanine (O6MeG) and N- methylpurines as
      critical lesions. For S(N)2 agents such as methyl- methanesulfonate (MMS), base N
      methylation lesions are most critical, likely because of the formation of
      apurinic sites blocking replication. For S(N)1 agents, such as N-methyl-N'-nitro
      N-nitrosoguanidine (MNNG), O6-methylguanine (O6MeG) plays the major role both in
      recombination and clastogenicity in the post-treatment cell cycle, provided the
      lesion is not pre-replicatively repaired by O6-methylguanine-DNA
      methyltransferase (MGMT). The conversion probability of O6MeG into SCEs and
      chromosomal aberrations is estimated to be about 30:1 and >10,000:1 respectively,
      indicating this mispairing pro-mutagenic lesion to be highly potent in inducing
      recombination giving rise to SCEs. O6MeG needs replication and mismatch repair to
      become converted into a critical secondary genotoxic lesion. Here it is proposed
      that this secondary lesion can be tolerated by a process termed recombination
      bypass. This process is supposed to be important in the tolerance of lesions that
      can not be processed by translesion synthesis accomplished by low-fidelity DNA
      polymerases. Recombination bypass results in SCEs and might represent an
      alternative pathway of tolerance of non-instructive lesions. In the case of O6MeG
      derived secondary lesions, recombination bypass appears to protect against cell
      killing since SCEs are already induced with low, non-toxic doses of MNNG.
      Saturation of lesion tolerance by recombination bypass or translesion synthesis
      may cause block of DNA replication leading to DSBs at stalled replication forks,
      which result in chromatid-type aberrations. Along with this model, several
      putative consequences of methylation-induced aberrations will be discussed such
      as cell death by apoptosis as well its role in tumor promotion and progression.

PMID- 15162019
TI  - Human fibroblasts expressing hTERT show remarkable karyotype stability even after
      exposure to ionizing radiation.
AB  - Ectopic expression of telomerase results in an immortal phenotype in various
      types of normal cells, including primary human fibroblasts. In addition to its
      role in telomere lengthening, telomerase has now been found to have various
      functions, including the control of DNA repair, chromatin modification, and the
      control of expression of genes involved in cell cycle regulation. The
      investigations on the long-term effects of telomerase expression in normal human
      fibroblast highlighted that these cells show low frequencies of chromosomal
      aberrations. In this paper, we describe the karyotypic stability of human
      fibroblasts immortalized by expression of hTERT. The ectopic overexpression of
      telomerase is associated with unusual spontaneous as well as radiation-induced
      chromosome stability. In addition, we found that irradiation did not enhance
      plasmid integration in cells expressing hTERT, as has been reported for other
      cell types. Long-term studies illustrated that human fibroblasts immortalized by
      telomerase show an unusual stability for chromosomes and for plasmid integration
      sites, both with and without exposure to ionizing radiation. These results
      confirm a role for telomerase in genome stabilisation by a telomere-independent
      mechanism and point to the possibility for utilizing hTERT-immortalized normal
      human cells for the study of gene targeting.

PMID- 15162020
TI  - Mechanisms of formation of chromosomal aberrations: insights from studies with
      DNA repair-deficient cells.
AB  - In order to understand the mechanisms of formation of chromosomal aberrations,
      studies performed on human syndromes with genomic instability can be fruitful. In
      this report, the results from studies in our laboratory on the importance of the
      transcription-coupled repair (TCR) pathway on the induction of chromosomal damage
      and apoptosis by ultraviolet light (UV) are discussed. UV61 cells (hamster
      homologue of human Cockayne's syndrome group B) deficient in TCR showed a
      dramatic increase in the induction of chromosomal aberrations and apoptosis
      following UV treatment. At relatively low UV doses, the induction of chromosomal
      aberrations preceded the apoptotic process. Chromosomal aberrations probably lead
      to apoptosis and most of the cells had gone through an S phase after the UV
      treatment before entering apoptosis. At higher doses of UV, the cells could go
      into apoptosis already in the G1 phase of the cell cycle. Abolition of TCR by
      treatment with alpha-amanitin (an inhibitor of RNA polymerase II) in the parental
      cell line AA8 also resulted in the induction of elevated chromosomal damage and
      apoptotic response similar to the one observed in UV61 cells treated with UV
      alone. This suggests that the lack of TCR is responsible for the increased
      frequencies of chromosomal aberrations and apoptosis in UV61 cells.
      Hypersensitivity to the induction of chromosomal damage by inhibitors of
      antitopoisomerases I and II in Werner's syndrome cells is also discussed in
      relation to the compromised G2 phase processes involving the Werner protein.

PMID- 15162021
TI  - In situ DNAse I sensitivity assay indicates DNA conformation differences between
      CHO cells and the radiation-sensitive CHO mutant IRS-20.
AB  - The radiosensitive mutant cell line IRS-20, its wild type counterpart CHO and a
      derivative of IRS-20 with a transfected YAC clone (YAC-IRS) that restores
      radioresistance were tested for DNAse I sensitivity. The three cell lines were
      cultured under the same conditions and had a mitotic index of 2-5%. One drop of
      fixed cells from the three lines was always spread on the same microscopic slide.
      After one day of ageing, slides were exposed to DNAse I and stained with DAPI.
      Images from every field were captured and the intensity of blue fluorescence was
      measured with appropriate software. For untreated cells, the fluorescence
      intensity was similar for all of the cell lines. After DNAse I treatment, CHO and
      YAC-IRS had an intensity of 85% but IRS-20 had an intensity of 60%, when compared
      with the controls. DNAse I sensitivity differences between the cell lines
      indicate that overall conformation of chromatin might contribute to radiation
      sensitivity of the IRS-20 cells.

PMID- 15162022
TI  - DNA damage processing and aberration formation in plants.
AB  - Various types of DNA damage, induced by endo- and exogenous genotoxic impacts,
      may become processed into structural chromosome changes such as sister chromatid
      exchanges (SCEs) and chromosomal aberrations. Chromosomal aberrations occur
      preferentially within heterochromatic regions composed mainly of repetitive
      sequences. Most of the preclastogenic damage is correctly repaired by different
      repair mechanisms. For instance, after N-methyl-N-nitrosourea treatment one SCE
      is formed per >40,000 and one chromatid-type aberration per approximately 25
      million primarily induced O6-methylguanine residues in Vicia faba. Double-strand
      breaks (DSBs) apparently represent the critical lesions for the generation of
      chromosome structural changes by erroneous reciprocal recombination repair.
      Usually two DSBs have to interact in cis or trans to form a chromosomal
      aberration. Indirect evidence is at hand for plants indicating that chromatid
      type aberrations mediated by S phase-dependent mutagens are generated by post
      replication (mis)repair of DSBs resulting from (rare) interference of repair and
      replication processes at the sites of lesions, mainly within repetitive sequences
      of heterochromatic regions. The proportion of DSBs yielding structural changes
      via misrepair has still to be established when DSBs, induced at predetermined
      positions, can be quantified and related to the number of SCEs and chromosomal
      aberrations that appear at these loci after DSB induction. Recording the degree
      of association of homologous chromosome territories (by chromosome painting) and
      of punctual homologous pairing frequency along these territories during and after
      mutagen treatment of wild-type versus hyperrecombination mutants of Arabidopsis
      thaliana, it will be elucidated as to what extent the interphase arrangement of
      chromosome territories becomes modified by critical lesions and contributes to
      homologous reciprocal recombination. This paper reviews the state of the art with
      respect to DNA damage processing in the course of aberration formation and the
      interphase arrangement of homologous chromosome territories as a structural
      prerequisite for homologous rearrangements in plants.

PMID- 15162024
TI  - DNA repair factors and telomere-chromosome integrity in mammalian cells.
AB  - Loss of telomere equilibrium and associated chromosome-genomic instability might
      effectively promote tumour progression. Telomere function may have contrasting
      roles: inducing replicative senescence and promoting tumourigenesis and these
      roles may vary between cell types depending on the expression of the enzyme
      telomerase, the level of mutations induced, and efficiency/deficiency of related
      DNA repair pathways. We have identified an alternative telomere maintenance
      mechanism in mouse embryonic stem cells lacking telomerase RNA unit (mTER) with
      amplification of non-telomeric sequences adjacent to existing short stretches of
      telomere repeats. Our quest for identifying telomerase-independent or alternative
      mechanisms involved in telomere maintenance in mammalian cells has implicated the
      involvement of potential DNA repair factors in such pathways. We have reported
      earlier on the telomere equilibrium in scid mouse cells which suggested a
      potential role of DNA repair proteins in telomere maintenance in mammalian cells.
      Subsequently, studies by us and others have shown the association between the DNA
      repair factors and telomere function. Mice deficient in a DNA-break sensing
      molecule, PARP-1 (poly [ADP]-ribopolymerase), have increased levels of
      chromosomal instability associated with extensive telomere shortening. Ku80 null
      cells showed a telomere shortening associated with extensive chromosome end
      fusions, whereas Ku80+/- cells exhibited an intermediate level of telomere
      shortening. Inactivation of PARP-1 in p53-/- cells resulted in dysfunctional
      telomeres and severe chromosome instability leading to advanced onset and
      increased tumour incidence in mice. Interestingly, haploinsufficiency of PARP-1
      in Ku80 null cells causes more severe telomere shortening and chromosome
      abnormalities compared to either PARP-1 or Ku80 single null cells and Ku80+/-PARP
      /- mice develop spontaneous tumours. This overview will focus mainly on the role
      of DNA repair/recombination and DNA damage signalling molecules such as PARP-1,
      DNA-PKcs, Ku70/80, XRCC4 and ATM which we have been studying for the last few
      years. Because the maintenance of telomere function is crucial for genomic
      stability, our results will provide new insights into the mechanisms of
      chromosome instability and tumour formation.

PMID- 15162023
TI  - DNA and telomeres: beginnings and endings.
AB  - How a cell deals with its DNA ends is a question that returns us to the very
      beginnings of modern telomere biology. It is also a question we are still asking
      today because it is absolutely essential that a cell correctly distinguishes
      between natural chromosomal DNA ends and broken DNA ends, then processes each
      appropriately - preserving the one, rejoining the other. Effective end-capping of
      mammalian telomeres has a seemingly paradoxical requirement for proteins more
      commonly associated with DNA double strand break (DSB) repair. Ku70, Ku80, DNA
      PKcs (the catalytic subunit of DNA-dependent protein kinase), Xrcc4 and Artemis
      all participate in DSB repair through nonhomologous end-joining (NHEJ). Somewhat
      surprisingly, mutations in any of these genes cause spontaneous chromosomal end
      to-end fusions that maintain large blocks of telomeric sequence at the points of
      fusion, suggesting loss or failure of a critical terminal structure, rather than
      telomere shortening, is at fault. Nascent telomeres produced via leading-strand
      DNA synthesis are especially susceptible to these end-to-end fusions, suggesting
      a crucial difference in the postreplicative processing of telomeres that is
      linked to their mode of replication. Here we will examine the dual roles played
      by DNA repair proteins. Our review of this rapidly advancing field primarily will
      focus on mammalian cells, and cannot include even all of this. Despite these
      limitations, we hope the review will serve as a useful gateway to the literature,
      and will help to frame the major issues in this exciting and rapidly progressing
      field. Our apologies to those whose work we are unable to include.

PMID- 15162025
TI  - Interstitial telomeric repeats are not preferentially involved in radiation
      induced chromosome aberrations in human cells.
AB  - Telomeric repeat sequences, located at the end of eukaryotic chromosomes, have
      been detected at intrachromosomal locations in many species. Large blocks of
      telomeric sequences are located near the centromeres in hamster cells, and have
      been reported to break spontaneously or after exposure to ionizing radiation,
      leading to chromosome aberrations. In human cells, interstitial telomeric
      sequences (ITS) can be composed of short tracts of telomeric repeats (less than
      twenty), or of longer stretches of exact and degenerated hexanucleotides, mainly
      localized at subtelomeres. In this paper, we analyzed the radiation sensitivity
      of a naturally occurring short ITS localized in 2q31 and we found that this
      region is not a hot spot of radiation-induced chromosome breaks. We then selected
      a human cell line in which approximately 800 bp of telomeric DNA had been
      introduced by transfection into an internal euchromatic chromosomal region in
      chromosome 4q. In parallel, a cell line containing the plasmid without telomeric
      sequences was also analyzed. Both regions containing the transfected plasmids
      showed a higher frequency of radiation-induced breaks than expected, indicating
      that the instability of the regions containing the transfected sequences is not
      due to the presence of telomeric sequences. Taken together, our data show that
      ITS themselves do not enhance the formation of radiation-induced chromosome
      rearrangements in these human cell lines.

PMID- 15162026
TI  - Lack of spontaneous and radiation-induced chromosome breakage at interstitial
      telomeric sites in murine scid cells.
AB  - Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient
      mammalian cells are sensitive to both spontaneous and radiation-induced
      chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are
      not known. To investigate factors that predispose ITSs to chromosome breakage we
      used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved
      in the repair of DNA double-strand breaks. Interestingly, our results revealed
      lack of both spontaneous and radiation-induced chromosome breakage at ITSs found
      in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs
      to chromosome breakage is associated with the functional DNA double-strand break
      repair machinery. To investigate if this is the case we used scid cells in which
      DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of
      ITSs in scid cells with functional DNA-PKcs, presumably through chromosome
      breakage at ITSs, but their unchanged frequency in positive and negative control
      cells. Therefore, our results indicate that the functional DNA double-strand
      break machinery is required for elevated sensitivity of ITSs to chromosome
      breakage. Interestingly, we observed significant differences in mitotic
      chromosome condensation between scid cells and their counterparts with restored
      DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect
      in chromatin organization. Increased condensation of mitotic chromosomes in the
      scid background was also confirmed in vivo. Therefore, our results indicate a
      previously unanticipated role of DNA-PKcs in chromatin organisation, which could
      contribute to the lack of ITS sensitivity to chromosome breakage in murine scid
      cells.

PMID- 15162027
TI  - Cytological indications of the complex subtelomeric structure.
AB  - Research on the subtelomeric region has considerably increased because this
      chromosome segment (1) keeps the chromosome number constant, (2) intervenes in
      cancer and cell senescence processes, (3) presents more crossovers than other
      regions of the genome and, (4) is the site of cryptic chromosome aberrations
      associated with mental retardation and congenital malformations. Quantitative
      microphotometrical scanning and computer graphic image analysis enables the
      detection of differentially distributed Giemsa-stained structures in T-banded
      subtelomeric segments of human and Chinese hamster ovary (CHO) chromosomes. The
      presence of high density stain patterns in the subtelomeric region was confirmed
      using endoreduplicated chromosomes as a model. Besides, prolonging the incubation
      in the T-buffer, specific holes were induced in subtelomeric segments. Hole
      specificity was confirmed inducing them in complex CHO chromosome aberrations
      obtained by AluI. The method was also used to detect minute sister chromatid
      exchanges in the T-banded subtelomeric area (t-SCEs). The presence of t-SCEs was
      suspected to reflect, at the microscope level, the high crossover activity
      prevailing in the region. Due to the fact that the fluorescent signals obtained
      with subtelomeric probes seem to be colocalized with subtelomeric high density
      areas, measurements on the position of both structures with respect to the
      diffraction and chromosome edges were carried out. Data obtained showed
      comparable values suggesting that the high density segments were located where
      telomeric probes usually fluoresce. The possible relationship of the high density
      patterns, the production of specific holes, the localization of fluorescent areas
      and the detection of minute SCEs in the subtelomeric segment observed in T-banded
      CHO and human chromosomes is briefly reviewed.

PMID- 15162028
TI  - Quantitative analysis of radiation-induced chromosome aberrations.
AB  - We review chromosome aberration modeling and its applications, especially to
      biodosimetry and to characterizing chromosome geometry. Standard results on
      aberration formation pathways, randomness, dose-response, proximity effects,
      transmissibility, kinetics, and relations to other radiobiological endpoints are
      summarized. We also outline recent work on graph-theoretical descriptions of
      aberrations, Monte-Carlo computer simulations of aberration spectra, software for
      quantifying aberration complexity, and systematic links of apparently incomplete
      with complete or truly incomplete aberrations.

PMID- 15162029
TI  - Models of chromosome aberration induction: an example based on radiation track
      structure.
AB  - A few examples of models of chromosome aberration induction are summarised and
      discussed on the basis of the three main theories of aberration formation, that
      is "breakage-and-reunion", "exchange" and "one-hit". A model and code developed
      at the Universities of Milan and Pavia is then presented in detail. The model
      provides dose-response curves for different aberration types (dicentrics,
      translocations, rings, complex exchanges and deletions) induced in human
      lymphocytes by gamma rays, protons and alpha particles of different energies,
      both as monochromatic fields and as mixed fields. The main assumptions are that
      only clustered - and thus severe - DNA breaks ("Complex Lesions", CL) can
      participate in the production of aberrations, and that only break free ends in
      neighbouring chromosome territories can interact and form exchanges. The yields
      of CLs induced by the various radiation types of interest are taken from a
      previous modelling work. These lesions are distributed within a sphere
      representing the cell nucleus according to the radiation track structure, e.g.
      randomly for gamma rays and along straight lines for light ions. Interphase
      chromosome territories are explicitly simulated and configurations are obtained
      in which each chromosome occupies an intranuclear domain with volume proportional
      to its DNA content. In order to allow direct comparisons with experimental data,
      small fragments can be neglected since usually they cannot be detected in
      experiments. The presence of a background level of aberrations is also taken into
      account. The results of the simulations are in good agreement with experimental
      dose-response curves available in the literature, that provides a validation of
      the model both in terms of the adopted assumptions and in terms of the simulation
      techniques. To address the question of "true" incompleteness, simulations were
      also run in which all fragments were assumed to be visible.

PMID- 15162030
TI  - Virtual radiation biophysics: implications of nuclear structure.
AB  - The non-random positioning of chromosome territories (CTs) in lymphocyte cell
      nuclei has raised the question whether systematic chromosome-chromosome
      associations exist which have significant influence on interchange rates. In such
      a case the spatial proximity of certain CTs or even of clusters of CTs is
      expected to increase the respective exchange yields significantly, in comparison
      to a random association of CTs. In the present study we applied computer
      simulated arrangements of CTs to calculate interchange frequencies between all
      heterologous CT pairs, assuming a uniform action of the molecular repair
      machinery. For the positioning of CTs in the virtual nuclear volume we assumed a)
      a statistical, and b) a gene density-correlated arrangement. The gene density
      correlated arrangement regards the more experimentally observed interior
      localization of gene-rich and the more peripheral positioning of gene-poor CTs.
      Regarding one-chromosome yields, remarkable differences for single CTs were
      observed taking into account the gene density-correlated distribution of CTs.

PMID- 15162031
TI  - Dose dependency of FISH-detected translocations in stable and unstable cells
      after Cs gamma irradiation of human lymphocytes in vitro.
AB  - Human peripheral lymphocytes were exposed to 137Cs gamma-rays (0-4.3 Gy) in order
      to check the impact of unstable cells on the dose-response curve for
      translocations. Chromosomes 2, 4 and 8 were FISH-painted. 17,720 first dividing
      cells were analysed. For the discrimination between stable and unstable cells the
      painted and the counter-stained chromosomes were analysed at doses of 1 Gy and
      higher. The cell distribution of translocations follows a Poisson distribution.
      The data were fitted to the linear-quadratic function, y = c + alphaD + betaD2.
      As expected, the alpha coefficients of the dose-response curves for
      translocations in stable cells or in total cells do not differ. However, at doses
      >1 Gy, the frequency of all translocations in stable cells seems to be lower than
      the frequency in total cells. For the establishment of calibration curves for
      past dose assessment purposes, only complete translocations should be scored, in
      order to estimate reliable doses.

PMID- 15162032
TI  - Effect of DMSO on radiation-induced chromosome aberrations analysed by FISH.
AB  - The purpose of the present work was to determine if the described reduction in
      the frequency of radiation-induced chromosome aberrations by DMSO is homogeneous
      within different human chromosomes. Blood samples were irradiated with 4 Gy of X
      rays in absence and presence of 0.5 M DMSO. FISH painting was carried out
      independently for human chromosomes 1, 2, 3, 4, 7, 11 and 12. The observed
      frequencies of apparently simple translocations and dicentrics for all these
      chromosomes, showed a homogeneous reduction when the irradiation was done in the
      presence of DMSO. Moreover, a better fit between the observed and expected
      frequencies was obtained when (DNA content)2/3 was used to calculate the expected
      frequencies, instead of just the DNA content. This result supports the idea that
      for exchange type aberrations, a better adjustment is obtained when the surface
      area of spherical chromosome territories is considered.

PMID- 15162033
TI  - DNA damage in Chinese hamster cells repeatedly exposed to low doses of X-rays.
AB  - In a recent paper we reported the results of an experiment carried out by
      analysing chromosomal damage in Chinese hamster (CHO) cells exposed to low doses
      of X-rays. The present investigation was undertaken in order to validate those
      results using a different approach, the single cell gel electrophoresis assay
      (comet assay) immediately after irradiation. Cells were cultured during 14
      cycles, irradiation treatment was performed once per cycle when the cells were at
      90-95% of confluence. Doses of 2.5, 5.0 and 10.0 mSv were used. Sequential
      irradiation of CHO cells induced a decrease of cells without migration and an
      increase of cells showing DNA damage with the three doses employed. Significant
      increases of low-level damaged cells (p < 0.001) were found for the 14 exposures
      when compared to controls except for the first irradiations with 2.5 and 10 mSv,
      respectively. No significant increase of the frequency of cells with severe
      damage was observed in any case. These findings could be explained by assuming a
      complex interactive process of cell recovery, DNA damage and repair together with
      the induction of genomic instability, the incidence of bystander effects as well
      as some kind of radioadaptative response of the cells. If these phenomena are
      limited to the cell line employed deserves further investigation.

PMID- 15162034
TI  - Potassium bromate but not X-rays cause unexpectedly elevated levels of DNA
      breakage similar to those induced by ultraviolet light in Cockayne syndrome (CS
      B) fibroblasts.
AB  - It has been previously reported that the elevated accumulation of repair incision
      intermediates in cells from patients with combined characteristics of xeroderma
      pigmentosum complementation group D (XP-D) and Cockayne syndrome (CS) XP-D/CS
      fibroblasts following UV irradiation is caused by an "uncontrolled" incision of
      undamaged genomic DNA induced by UV-DNA-lesions which apparently are not removed.
      This could be an explanation for the extreme sensitivity of these cells to UV
      light. In the present study, we confirm the immediate DNA breakage following UV
      irradiation also for CS group B (CS-B) fibroblasts by DNA migration in the "comet
      assay" and extend these findings to other lesions such as 8-oxodeoxyguanosine (8
      oxodG), selectively induced by KBrO3 treatment. In contrast, X-ray exposure does
      not induce differential DNA breakage. This indicates that additional lesions
      other than the UV-induced photoproducts (cyclobutane pyrimidine dimers, CPD, and
      6-pyrimidine-4-pyrimidone products, 6-4 PP), such as 8-oxodG, specifically
      induced by KBrO3, are likely to trigger "uncontrolled" DNA breakage in the
      undamaged genomic DNA in the CS-B fibroblasts, thus accounting for some of the
      clinical features of these patients.

PMID- 15162035
TI  - Distribution of breakpoints induced by etoposide and X-rays along the CHO X
      chromosome.
AB  - SORB (selected observed residual breakpoints) induced by ionizing radiation or
      endonucleases are often non-randomly distributed in mammalian chromosomes.
      However, the role played by chromatin structure in the localization of chromosome
      SORB is not well understood. Anti-topoisomerase drugs such as etoposide are
      potent clastogens and unlike endonucleases or ionizing radiation, induce DNA
      double-strand breaks (DSB) by an indirect mechanism. Topoisomerase II (Topo II)
      is a main component of the nuclear matrix and the chromosome scaffold. Since
      etoposide leads to DSB by influencing the activity of Topo II, this compound may
      be a useful tool to study the influence of the chromatin organization on the
      distribution of induced SORB in mammalian chromosomes. In the present work, we
      compared the distribution of SORB induced during S-phase by etoposide or X-rays
      in the short euchromatic and long heterochromatic arms of the CHO9 X chromosome.
      The S-phase stage (early, mid or late) at which CHO9 cells were exposed to
      etoposide or X-rays was marked by incorporation of BrdU during treatments and
      later determined by immunolabeling of metaphase chromosomes with an anti-BrdU
      FITC-coupled antibody. The majority of treated cells were in late S-phase during
      treatment either with etoposide or X-rays. SORB induced by etoposide mapped
      preferentially to Xq but random localization was observed for SORB produced by X
      rays. Possible explanations for the uneven distribution of etoposide-induced
      breakpoints along Xq are discussed.

PMID- 15162036
TI  - The repair of gamma-ray-induced chromosomal damage in human lymphocytes after
      exposure to extremely low frequency electromagnetic fields.
AB  - G(0) human blood lymphocytes were irradiated with 2.0 Gy gamma-rays and cultured
      to metaphase whilst held in a 50-Hz power frequency magnetic field of 0.23, 0.47
      or 0.7 mT. No differences were found in the frequencies of gamma-induced
      chromosome aberrations observed in cells held in the EM fields compared with
      replicates held in a sham coil. Similar field conditions have been reported to
      increase the frequency of gamma-induced HPRT mutations, leading to a suggestion
      that the EM fields alter the fidelity of repair of genomic lesions. This was not
      confirmed by the chromosome aberration assay described here.

PMID- 15162037
TI  - Ionizing radiation-induced instant pairing of heterochromatin of homologous
      chromosomes in human cells.
AB  - Using fluorescence in situ hybridization with human band-specific DNA probes we
      examined the effect of ionizing radiation on the intra-nuclear localization of
      the heterochromatic region 9q12-->q13 and the euchromatic region 8p11.2 of
      similar sized chromosomes 9 and 8 respectively in confluent (G1) primary human
      fibroblasts. Microscopic analysis of the interphase nuclei revealed
      colocalization of the homologous heterochromatic regions from chromosome 9 in a
      proportion of cells directly after exposure to 4 Gy X-rays. The percentage of
      cells with paired chromosomes 9 gradually decreased to control levels during a
      period of one hour. No significant changes in localization were observed for
      chromosome 8. Using 2-D image analysis, radial and inter-homologue distances were
      measured for both chromosome bands. In unexposed cells, a random distribution of
      the chromosomes over the interphase nucleus was found. Directly after
      irradiation, the average inter-homologue distance decreased for chromosome 9
      without alterations in radial distribution. The percentage of cells with inter
      homologue distance <3 micro m increased from 11% in control cells to 25% in
      irradiated cells. In contrast, irradiation did not result in significant changes
      in the inter-homologue distance for chromosome 8. Colocalization of the
      heterochromatic regions of homologous chromosomes 9 was not observed in cells
      irradiated on ice. This observation, together with the time dependency of the
      colocalization, suggests an underlying active cellular process. The biological
      relevance of the observed homologous pairing remains unclear. It might be related
      to a homology dependent repair process of ionizing radiation induced DNA damage
      that is specific for heterochromatin. However, also other more general cellular
      responses to radiation-induced stress or change in chromatin organization might
      be responsible for the observed pairing of heterochromatic regions.

PMID- 15162038
TI  - Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a
      review of three recent radiation accidents.
AB  - The analysis of chromosomal aberrations in peripheral blood of radiation accident
      victims is an established method of biological dosimetry. The dose estimate on
      the basis of an in vitro calibration curve is straightforward when the radiation
      exposure is homogeneous and the analysis not delayed. In recent years three
      radiation accidents occurred, where the irradiation or sampling conditions
      precluded a simple estimation of the dose. During the Georgian accident soldiers
      carried in their pockets small sources of 137Cs leading to partial and protracted
      body exposures. During the Tokai-mura accident, three employees involved in the
      process of 235U enrichment were exposed to very high doses of gamma rays and
      neutrons. During the Bialystok accident, five patients with breast cancer
      undergoing radiotherapy were exposed to a single dose of electrons which reached
      about 100 Gy. In the present paper the approaches chosen to estimate, by
      cytogenetic methods, the doses absorbed by the people involved in the accidents
      are described.

PMID- 15162039
TI  - Complex chromatid-isochromatid exchanges following irradiation with heavy ions?
AB  - We describe a peculiar and relatively rare type of chromosomal rearrangement
      induced in human peripheral lymphocytes that were ostensibly irradiated in G(0)
      phase of the cell cycle by accelerated heavy ions, and which, to the best of our
      knowledge, have not been previously described. The novel rearrangements which
      were detected using mFISH following exposure to 500 MeV/nucleon and 5 GeV/n 56Fe
      particles, but were not induced by either 137Cs gamma rays or 238Pu alpha
      particles, can alternatively be described as either complex chromatid
      isochromatid or complex chromatid-chromosome exchanges. Different mechanisms
      potentially responsible for their formation are discussed.

PMID- 15162040
TI  - G2 chromatid damage and repair kinetics in normal human fibroblast cells exposed
      to low- or high-LET radiation.
AB  - Radiation-induced chromosome damage can be measured in interphase using the
      Premature Chromosome Condensation (PCC) technique. With the introduction of a new
      PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can
      be condensed within five minutes, and it is now possible to examine the early
      damage induced by radiation. Using this method, it has been shown that high-LET
      radiation induces a higher frequency of chromatid breaks and a much higher
      frequency of isochromatid breaks than low-LET radiation. The kinetics of
      chromatid break rejoining consists of two exponential components representing a
      rapid and a slow time constant, which appears to be similar for low- and high-LET
      radiations. However, after high-LET radiation exposures, the rejoining process
      for isochromatid breaks influences the repair kinetics of chromatid-type breaks,
      and this plays an important role in the assessment of chromatid break rejoining
      in the G2 phase of the cell cycle.

PMID- 15162041
TI  - Cytogenetic effects of densely ionising radiation in human lymphocytes: impact of
      cell cycle delays.
AB  - The classical cytogenetic assay to estimate the dose to which an individual has
      been exposed relies on the measurement of chromosome aberrations in lymphocytes
      at the first post-irradiation mitosis 48 h after in vitro stimulation. However,
      evidence is accumulating that this protocol results in an underestimation of the
      cytogenetic effects of high LET radiation due to a selective delay of damaged
      cells. To address this issue, human lymphocytes were irradiated with C-ions (25
      mm extended Bragg peak, LET: 60-85 keV/ micro m) and aberrations were measured in
      cells reaching the first mitosis after 48, 60, 72 and 84 h and in G2-phase cells
      collected after 48 h by calyculin A induced premature chromosome condensation
      (PCC). The results were compared with recently published data on the effects of X
      rays and 200 MeV/u Fe-ions (LET: 440 keV/ micro m) on lymphocytes of the same
      donor (Ritter et al., 2002a). The experiments show clearly that the aberration
      yield rises in first-generation metaphase (M1) with culture time and that this
      effect increases with LET. Obviously, severely damaged cells suffer a prolonged
      arrest in G2. The mitotic delay has a profound effect on the RBE: RBE values
      estimated from the PCC data were about two times higher than those obtained by
      conventional metaphase analysis at 48 h. Altogether, these observations argue
      against the use of single sampling times to quantify high LET induced chromosomal
      damage in metaphase cells.

PMID- 15162042
TI  - Chromosome aberrations induced by high-LET carbon ions in radiosensitive and
      radioresistant tumour cells.
AB  - Chromosome aberration formation was analysed in two human tumour cell lines
      displaying different radiosensitivity. Aberrations involving chromosomes 2, 4,
      and 5 were studied in one radioresistant cell line (WiDr) and in one
      radiosensitive cell line (MCF-7). Chromosome aberrations were studied by
      application of single-colour FISH. We studied the effects of monoenergetic 100
      MeV/u carbon ions and carbon ions from extended Bragg peak. Chromosome
      aberrations induced by carbon ions were compared with aberrations induced by
      standard 200 kV X-rays. In both tumour cell lines, carbon ions induced
      aberrations more effectively than X-rays. The radioresistance and
      radiosensitivity of the corresponding cell lines, as observed for X-rays, were
      also found after carbon ion irradiation. In both cell lines, the typical effects
      of ion irradiation were an increased proportion of cells containing complex
      aberrations, and an increased complexity of these complex exchanges. However,
      comparable effects were induced in MCF-7 cells by a much lower dose than in WiDr
      cells. Insertions were also induced more efficiently in MCF-7 cells than in WiDr
      cells.

PMID- 15162043
TI  - Induction of homologous recombination in the hprt gene of V79 Chinese hamster
      cells in response to low- and high-LET irradiation.
AB  - Dense ionization tracks from high linear energy transfer (LET) radiations form
      multiple damaged sites (MDS), which involve several types of DNA lesions in close
      vicinity. The primary DNA damage triggers sensor proteins that activate repair
      processes, cell cycle control or eventually apoptosis in subsequent cellular
      responses. The question how homologous recombination (HR) and non-homologous end
      joining (NHEJ) interact in the repair of radiation-induced DNA damage of MDS type
      has been addressed in different model systems but several questions remain to be
      answered. We have therefore challenged cells with treatments of ionizing
      radiation of different qualities to investigate whether primary DNA damages of
      different complexity are reflected in the processes of repair by HR as well as
      cell survival. We used the V79 derived SPD8 cell line to determine the induction
      of HR in the hprt exon 7 and clonogenic assay for survival in response to
      radiation. SPD8 cells were irradiated with gamma-rays (137Cs 0.5 keV/microm),
      boron ions (40 and 80 keV/microm) and nitrogen ions (140 keV/microm), with doses
      up to 5 Gy. Analysis of clonogenic survival showed that B-ions (80 keV/microm)
      and N-ions were more toxic than gamma-rays, 4.1 and 5.0 times respectively, while
      B-ions at 40 keV/microm were 2.0 times as toxic as gamma-rays. Homologous
      recombination in the cells exposed to B-ions (80 keV/microm) increased 2.9 times,
      a significant response as compared to cells exposed to gamma-rays, while for B
      ions (40 keV/microm) and N-ions a nonsignificant increase in HR of 1.2 and 1.4,
      respectively, was observed. We hypothesize that the high-LET generated formation
      of MDS is responsible for the enhanced cytotoxicity as well as for the
      mobilization of the HR machinery.

PMID- 15162044
TI  - Cytogenetic analyses in peripheral lymphocytes of persons living in houses with
      increased levels of indoor radon concentrations.
AB  - Published data concerning the effects of indoor radon exposure on the frequency
      of chromosome aberrations in peripheral lymphocytes of residents are
      contradictory. Possible reasons for this may be the low radon concentration in
      dwellings and/or the limited number of investigated persons. We therefore studied
      the relationship of domestic radon exposure and the occurrence of chromosome
      aberrations in peripheral lymphocytes in 61 persons living in houses with radon
      concentrations from 80 up to 13,000 Bq/m3. We analyzed 60,000 cells from
      fluorescence plus Giemsa (FPG)-stained slides. It could be clearly demonstrated
      that in groups of persons living in dwellings with indoor radon concentrations
      >200 Bq/m3 the number of cells containing dicentrics and/or centric rings (C(dic
      + cr)) (2.45 +/- 0.50 x 10(-3)) was significantly increased (p < 0.05) in
      comparison to the control level (1.03 +/- 0.15 x 10(-3)). However, there was no
      difference in the mean frequency of C(dic + cr) between the groups living in
      dwellings with higher radon concentrations. Using the fluorescence in situ
      hybridization (FISH) technique for the detection of translocations, we analyzed
      23,315 cells in 16 persons of the highest exposed group (>5,000 Bq/m3). The
      observed frequency of translocations was 3.9 +/- 0.64 x 10(-3). In comparison to
      the control group (2.02 +/- 0.18 x 10(-3)), there was a slight but not
      statistically significant increase in the exposed group (P = 0.055). If, however,
      the age of the examined persons is taken into account, the values are
      significantly increased (P < 0.05) in the exposed persons older than 40 years in
      comparison to the age-matched controls. Since most of the translocations were
      found in stable cells, it is concluded that translocations are also induced in
      blood-forming tissue and are transmitted to peripheral blood.

PMID- 15162045
TI  - Effect of high-level natural radiation on chromosomes of residents in southern
      China.
AB  - To study the effect of low-dose (rate) radiation on human health, we analyzed
      chromosomes of peripheral lymphocytes of residents in a high background radiation
      area (HBRA) and compared the results with those obtained from residents in a
      control area (CA) in Guangdong Province, China. Unstable types of chromosome
      aberrations (dicentrics and rings) were studied in 22 members of eight families
      in HBRA and 17 members of five families in CA. Each family consists of three
      generations. On average 2,600 cells per subject were analyzed. 27 adults and six
      children in HBRA and 25 adults and eight children in CA were studied with respect
      to translocations. On average 4,741 cells per subject were examined. We found an
      increase of the frequency of dicentrics and rings in HBRA, where the natural
      radiation level is three to five times higher than in the control area. But the
      increase of translocations in HBRA was within the range of individual variation
      in the controls.

PMID- 15162046
TI  - Complex chromosomal rearrangements induced in vivo by heavy ions.
AB  - It has been suggested that the ratio complex/simple exchanges can be used as a
      biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo,
      by considering data from several studies that measured complex exchanges in
      peripheral blood from humans exposed to mixed fields of low- and high-LET
      radiation. In particular, we studied data from astronauts involved in long-term
      missions in low-Earth-orbit, and uterus cancer patients treated with accelerated
      carbon ions. Data from two studies of chromosomal aberrations in astronauts used
      blood samples obtained before and after space flight, and a third study used
      blood samples from patients before and after radiotherapy course. Similar methods
      were used in each study, where lymphocytes were stimulated to grow in vitro, and
      collected after incubation in either colcemid or calyculin A. Slides were painted
      with whole-chromosome DNA fluorescent probes (FISH), and complex and simple
      chromosome exchanges in the painted genome were classified separately. Complex
      type exchanges were observed at low frequencies in control subjects, and in our
      test subjects before the treatment. No statistically significant increase in the
      yield of complex-type exchanges was induced by the space flight. Radiation
      therapy induced a high fraction of complex exchanges, but no significant
      differences could be detected between patients treated with accelerated carbon
      ions or X-rays. Complex chromosomal rearrangements do not represent a practical
      biomarker of radiation quality in our test subjects.

PMID- 15162047
TI  - Chromosome aberrations of clonal origin are present in astronauts' blood
      lymphocytes.
AB  - Radiation-induced chromosome translocations remain in peripheral blood cells over
      many years, and can potentially be used to measure retrospective doses or
      prolonged low-dose rate exposures. However, several recent studies have indicated
      that some individuals possess clones of cells with balanced chromosome
      abnormalities, which can result in an overestimation of damage and, therefore,
      influence the accuracy of dose calculations. We carefully examined the patterns
      of chromosome damage found in the blood lymphocytes of twelve astronauts, and
      also applied statistical methods to screen for the presence of potential clones.
      Cells with clonal aberrations were identified in three of the twelve individuals.
      These clonal cells were present in samples collected both before and after space
      flight, and yields are higher than previously reported for healthy individuals in
      this age range (40-52 years of age). The frequency of clonal damage appears to be
      even greater in chromosomes prematurely condensed in interphase, when compared
      with equivalent analysis in metaphase cells. The individuals with clonal
      aberrations were followed-up over several months and the yields of all clones
      decreased during this period. Since clonal aberrations may be associated with
      increased risk of tumorigenesis, it is important to accurately identify cells
      containing clonal rearrangements for risk assessment as well as biodosimetry.

PMID- 15162049
TI  - Contribution of chromosomal imbalance to sperm selection and pre-implantation
      loss in translocation-heterozygous Chinese hamsters.
AB  - Chinese hamster stocks with various structurally abnormal chromosomes have been
      produced by X irradiation. Among these stocks, 18 with various reciprocal
      translocations were used to investigate the participation of unbalanced gametes
      in fertilization and the development of unbalanced embryos. Among males as well
      as females heterozygous for the same translocation, there is no difference in the
      frequency of each disjunctional class. The participation of chromosomally
      unbalanced gametes in fertilization was investigated by chromosomal analysis of
      meiotic cells in heterozygotes for the 18 reciprocal translocations and pronuclei
      of fertilized ova obtained from crossing these heterozygotes. Compared with the
      expected frequencies from MII scoring, the frequencies of male pronuclei having a
      common deficiency of chromosome 1 (1q17-->1q42) or chromosome 3 (3p23-->3q31)
      decreased significantly in one-cell embryos. However, the frequencies of male
      pronuclei with other abnormalities were all consistent with those expected from
      MII scoring. In contrast, the frequencies of female pronuclei with any karyotype
      including the same abnormalities as those decreased in male pronuclei from the
      translocation heterozygotes were all consistent with those estimated from MII
      scoring. These results revealed clearly that most gametes with nullisomies as
      well as disomies for any chromosomal segments may participate in fertilization,
      whereas only male gametes nullisomic for certain segments of chromosomes 1 and 3
      failed to participate in fertilization. The zygotic selection of chromosomal
      imbalance was also investigated by direct chromosomal and morphological analyses
      of preimplantation embryos from crosses between karyotypically normal females and
      male heterozygotes from the 18 stocks with various reciprocal translocations.
      These analyses revealed that some embryos were arrested in development at the two
      cell stage. The karyotype of these two-cell embryos had a common deficiency in a
      segment of chromosome 1 or chromosome 2. Embryos with partial monosomy including
      chromosomes 1, 3, 4 and 5 showed arrested development at four- to eight-cell
      stages. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a
      deficiency of segments of chromosomes 1p, 1q, 2q, 5q, 7q and 8, had fewer
      blastomeres than karyotypically normal and balanced embryos. The homology between
      Chinese hamster and mouse chromosomes relating to abnormal embryogenesis at early
      stages has been partially confirmed from reported maps of chromosomes. The
      Chinese hamster is useful for further cytogenetic studies during the stages of
      meiosis and early embryogenesis.

PMID- 15162048
TI  - Transgenerational transmission of radiation- and chemically induced tumors and
      congenital anomalies in mice: studies of their possible relationship to induced
      chromosomal and molecular changes.
AB  - This article provides a broad overview of our earlier studies on the induction of
      tumors and congenital anomalies in the progeny of X-irradiated or chemically
      treated mice and our subsequent (published, hitherto unpublished and on-going)
      investigations aimed at identifying potential relationships between genetic
      changes induced in germ cells and the adverse effects manifest as tumors and
      congenital anomalies using cytogenetic and molecular approaches. The earlier
      studies document the fact that tumors and congenital anomalies can be induced by
      irradiation or treatment with certain chemicals such as urethane and that these
      phenotypes are heritable i.e., transmitted to generations beyond the first
      generation. These findings support the view that transmissible induced genetic
      changes are involved. The induced rates of congenital abnormalities and tumors
      are about two orders of magnitude higher than those recorded in the literature
      from classical mutation studies with specific locus mutations. The cytogenetic
      studies addressed the question of whether there were any relationships between
      induced translocations and induced tumors. The available data permit the
      inference that gross chromosomal changes may not be involved but do not exclude
      smaller induced genetic changes that are beyond the resolution of the techniques
      used in these studies. Other work on possible relationship between visible
      chromosomal anomalies (in bone marrow preparations) and tumors were likewise
      negative. However, there were indications that some induced cytogenetic changes
      might underlie induced congenital anomalies, i.e., trisomies, deletions and
      inversions were observed in induced and transmissible congenital anomalies (such
      as dwarfs, tail anomalies). Studies that explored possible relationships between
      induction of minisatellite mutations at the Pc-3 locus and tumors were negative.
      However, gene expression analysis of tumor (hepatoma)-susceptible offspring of
      progeny descended from irradiated male mice showed abnormal expression of many
      genes. Of these, only very few were oncogenes. This lends some support to our
      hypothesis that cumulative changes in gene expression of many genes, which
      perform normal cellular functions, may contribute to the occurrence of tumors in
      the offspring of irradiated or chemically treated mice.

PMID- 15162050
TI  - Heritable translocations induced by dermal exposure of male mice to acrylamide.
AB  - Acrylamide (AA) is an important industrial chemical used mainly in the production
      of polymers. It can be absorbed through the skin. AA was shown to be a germ cell
      clastogen that entails a genetic risk for exposed workers. The genetic risk
      calculation was based on mouse heritable translocation test data obtained after
      acute intraperitoneal (ip) exposure (Adler et al., 1994). To obtain a correction
      factor between ip and dermal exposure, dominant lethal and heritable
      translocation tests were carried out with dermal exposure of male mice to AA. In
      the dominant lethal test, male (102/El x C3H/El)F1 mice were exposed by dermal
      application to the shaved backs of 50 mg/kg AA per day on five consecutive days
      or to five daily ip injections of 50 mg/kg AA. One day after the end of exposure,
      the males were mated to untreated females of the same hybrid stock for four days
      and females were changed every four days for a total of five matings. Dominant
      lethal effects were found during matings 1-3. For ip exposure, these values were
      81.7, 85.7 and 45.4%, respectively; for dermal exposure the corresponding values
      were 22.1, 30.6 and 16.5%, respectively. In the heritable translocation assay,
      male C3H/El mice were treated with five dermal exposures of 50 mg/kg AA and mated
      1.5-8.5 days after the end of exposure to untreated female 102/El mice. Pregnant
      females were allowed to come to term and all offspring were raised to maturity.
      Translocation carriers among the F1 progeny were selected by a sequential
      fertility testing and cytogenetic analysis including G-band karyotyping and M
      FISH. A total of 475 offspring were screened and 41 translocation carriers were
      identified. The observed translocation frequency after dermal exposure was 8.6%
      as compared to 21.9% after similar ip exposure (Adler, 1990). The calculated
      ratio of ip vs. dermal exposure of 0.39 can be applied to obtain a more realistic
      calculation of genetic risk for dermally exposed workers.

PMID- 15162051
TI  - Chromosome banding in Amphibia. XXX. Karyotype aberrations in cultured fibroblast
      cells.
AB  - The present study reports for the first time on the numerical and structural
      chromosome anomalies that spontaneously arise in aging cultured fibroblast cells
      of Amphibia. The analyses were conducted on kidney fibroblasts of three anuran
      species with extremely divergent genome sizes (Bufo rubropunctatus, Scaphiopus
      holbrooki, Gastrotheca riobambae), in the sixth up to the 14th culture passage.
      The chromosomal rearrangements were identified by means of the 5
      bromodeoxyuridine/deoxythymidine (BrdU/dT) replication banding technique. The
      aberrations can be either confined to a single chromosome, or else involve all
      chromosomes of the karyotype. The most frequent structural aberrations in the
      cell cultures of S. holbrooki and G. riobambae are tandem fusions between two or
      more chromosomes. These tandem fusions originating in vitro in long-termed cell
      cultures reflect the chromosome mutations which also took place during amphibian
      phylogenesis.

PMID- 15162052
TI  - Investigations into the biological relevance of in vitro clastogenic and
      aneugenic activity.
AB  - In the current study we present a view of events leading to chemically induced
      DNA damage in vitro from both a cytogenetic and molecular aspect, focusing on
      threshold mediated responses and the biological relevance of DNA damaging events
      that occur at low and high cellular toxicity levels. Current regulatory
      mechanisms do not take into account chemicals that cause significant DNA damage
      only at high toxicity. Our results demonstrate a defined threshold for
      micronucleus induction after insult with the alkylating agent MMS. Other results
      define a significant change in gene expression following treatment with chemicals
      that give rise to structural DNA damage only at high toxicity. Pairs of chemicals
      with a similar mode of action but differing toxicity levels were chosen, the
      chemicals that demonstrated structural DNA damage only at high levels of toxicity
      showed an increase in heat shock protein gene expression whereas the chemicals
      causing DNA damage events at all levels of toxicity did not induce changes in
      heat shock gene expression at identical toxicity levels. The data presented
      indicates that there are a number of situations where the linear dose response
      model is not appropriate for risk estimation. However, deviation from linear risk
      models should be dependent upon the availability of appropriate experimental data
      such as that shown here.

PMID- 15162053
TI  - Region-specific chromatin decondensation and micronucleus formation induced by 5
      azacytidine in human TIG-7 cells.
AB  - A human diploid lung fibroblast cell strain, TIG-7, has a heteromorphic
      chromosome 15 with an extra short arm carrying a homogeneously staining region
      (15p+hsr). We demonstrated previously that the 15p+hsr consists of an inactive
      and G+C-rich rDNA cluster characterized by fluorescence in situ hybridization
      (FISH) and various chromosome banding techniques. Thus, it was suggested that the
      region could contain highly methylated DNA. To observe methylation status on the
      target region directly under the microscope, we used a demethylating agent, 5
      azacytidine (5-azaC), to induce decondensation of the chromatin containing
      methylated DNA. At 24 h after treatment with 0.5 microM 5-azaC, marked
      decondensation of the 15p+hsr was observed in almost all of the metaphases.
      Furthermore, we observed micronuclei, which were equivalent to the rDNA of the
      15p+hsr demonstrated by FISH in the same preparation. In contrast, the DNA cross
      linking agent mitomycin C (MMC) preferentially induced 15p+hsr-negative
      micronuclei. These findings indicated that chromatin decondensation and
      subsequent DNA strand breakage induced by the demethylating effect of 5-azaC led
      specifically to 15p+hsr-positive micronuclei.

PMID- 15162054
TI  - Micronuclei in lymphocytes of uranium miners of the former Wismut SDAG.
AB  - We studied micronucleus frequencies in former German uranium miners of the Wismut
      SDAG (Sowjetisch-Deutsche Aktiengesellschaft). Various other groups were analyzed
      for comparison (individuals with lung tumors or lung fibrosis, controls). We had
      shown previously that micronucleus frequencies were not different among the
      various groups. Differences were observed, however, when centromere-positive and 
      negative micronuclei were distinguished. In the analyses presented here, we
      looked for the effects of smoking habits, alcohol consumption, vitamin uptake,
      chronic diseases, allergies, doing sports, gamma-GT (gamma
      glutamyltranspeptidase), lymphocyte numbers, CEA (carcinoembryonic antigen), X
      ray diagnostics, computer tomographies, and scintigraphies. With the exception of
      more than one scintigraphy carried out during the last four months before
      micronucleus analysis, none of the factors mentioned above significantly affected
      micronucleus numbers. One result deserves specific attention: individuals with
      low percentages of binucleated lymphocytes after in vitro cytochalasin B exposure
      showed higher micronucleus frequencies than those individuals with high
      percentages of binucleated cells. The same result was obtained for various other
      populations that we monitored in the past.

PMID- 15162055
TI  - A liver micronucleus assay using young rats exposed to diethylnitrosamine:
      methodological establishment and evaluation.
AB  - We have developed a simple liver micronucleus assay using young rats (up to 4
      weeks old) to assess cytogenetic damage of chemicals in liver cells.
      Diethylnitrosamine (DEN) was used as a model rodent hepatocarcinogen in this
      study. Compared to the partial hepatectomy method most commonly used for the
      liver micronucleus assay, the present assay method showed equal or even higher
      practicability. The young rat liver micronucleus assay was also characterized for
      rat strain differences, sampling time after treatment, single treatment vs. split
      treatment, age of animals, administration route, and staining method. Although
      based on one model chemical, we propose an acceptable protocol for the
      micronucleus assay using young rat liver as follows: Up to 4-week-old rats should
      be used; oral or intraperitoneal administration can be used; single or repeated
      treatment protocols can be applied; sampling time is 3-5 days after the last
      treatment; hepatocytes are prepared by the collagenase perfusion method; and
      cells are stained with the AO-DAPI double staining method.

PMID- 15162057
TI  - Frequent occurrence of UVB-induced sister chromatid exchanges in telomere regions
      and its implication to telomere maintenance.
AB  - Sister chromatid exchanges (SCEs) are symmetrical exchanges between newly
      replicated chromatids and their sisters. While homologous recombination may be
      one of the principal mechanisms responsible for SCEs, the full details of their
      molecular basis and biological significance remain to be elucidated. Following
      exposure to ultraviolet light B (UVB), mitomycin C (MMC) and cisplatin, we
      analyzed the location of SCEs on metaphase chromosomes in Chinese hamster CHO
      cells. The frequency of SCEs increased over the spontaneous level in proportion
      to the agent's dose. UVB-induced SCEs occurred frequently in telomere regions, as
      cisplatin-induced SCEs did, differing from MMC-induced ones. The remarkable
      difference of intrachromosomal distribution among the three mutagens may be
      attributed to the specificity of induced DNA lesions and structures of different
      chromosome regions. Telomeric DNA at the end of chromosomes is composed of
      multiple copies of a repeated motif, 5'-TTAGGG-3' in mammalian cells. Telomeric
      repeats may be potential targets for UVB and cisplatin, which mainly form
      pyrimidine dimers and intrastrand d(GpG) cross-links, respectively, resulting in
      SCE formation. UVB irradiation shortened telomeres and augmented the telomerase
      activity. The possible implications of the frequent occurrence of SCEs in
      telomere regions are discussed in connection with the maintenance of telomere
      integrity.

PMID- 15162056
TI  - Insights into the mechanisms of sister chromatid exchange formation.
AB  - The DNA lesions responsible for the formation of sister chromatid exchanges
      (SCEs) have been the object of research for a long time. SCEs can be visualized
      by growing cells for either two rounds of replication in the presence of 5-bromo
      2'-deoxyuridine (BrdU) or for one round with BrdU and the next without. If BrdU
      is added after cells were treated with a DNA-damaging agent, the effect on SCEs
      can only be analyzed in the second post-treatment mitosis. If one wishes to
      analyze the first post-treatment mitosis, cells unifilarily labeled with BrdU
      must be treated. Due to the highly reactive bromine atom, BrdU interacts with
      such agents like ionizing and UV radiation enhancing the frequency of SCEs.
      However, its precise role in this process was difficult to assess for a long
      time, because no alternative technique existed that allowed differential staining
      of chromatids. We have recently developed a method to differentially label sister
      chromatids with biotin-16-2'-deoxyuridine-5'-triphosphate (biotin-dUTP)
      circumventing the disadvantage of BrdU. This technique was applied to study the
      SCEs induced by ionizing and UV radiation as well as by mitomycin C, DNaseI and
      AluI. This article is a review of the results and conclusions of our previous
      studies.

PMID- 15162058
TI  - SCE analysis in G2 lymphocyte prematurely condensed chromosomes after exposure to
      atrazine: the non-dose-dependent increase in homologous recombinational events
      does not support its genotoxic mode of action.
AB  - Several studies have been carried out to evaluate the mutagenic and carcinogenic
      potential of atrazine, the most prevalent of triazine herbicides classified as a
      "possible human carcinogen". The majority of these studies have been negative but
      positive responses have been also reported including mammary tumors in female
      Sprague-Dawley rats. Sister chromatid exchanges (SCEs) caused by the presence of
      DNA lesions at the moment of DNA replication have been extensively used for
      genotoxicity testing, but for non-cytotoxic exposures to atrazine controversial
      results have been reported. Even though exposures to higher concentrations of
      atrazine could provide clear evidence for its genotoxicity, conventional SCE
      analysis at metaphase cells cannot be used because affected cells are delayed in
      G2-phase and do not proceed to mitosis. As a result, the genotoxic potential of
      atrazine may have been underestimated. Since clear evidence has been recently
      reported relating SCEs to homologous recombinational events, we are testing here
      the hypothesis that high concentrations of atrazine will cause a dose-dependent
      increase in homologous recombinational events as quantified by the frequency of
      SCEs analyzed in G2-phase. Towards this goal, a new cytogenetic approach is
      applied for the analysis of SCEs directly in G2-phase prematurely condensed
      chromosomes (PCCs). The methodology enables the visualization of SCEs in G2
      blocked cells and is based on drug-induced PCCs in cultured lymphocytes. The
      results obtained for high concentrations of atrazine do not demonstrate a dose
      dependent increase in homologous recombinational events. They do not support,
      therefore, a genotoxic mode of action. However, they suggest that an important
      part in the variation of SCE frequency reported by different laboratories when
      conventional SCE analysis is applied after exposure to a certain concentration of
      atrazine, is due to differences in cell cycle kinetics of cultured lymphocytes,
      rather than to a true biological variation in the cytogenetic end point used.

PMID- 15162059
TI  - X chromosome inactivation-mediated cellular mosaicism for the study of the
      monoclonal origin and recurrence of mouse tumors: a review.
AB  - X chromosome inactivation-mediated cellular mosaicism was applied to study the
      clonal nature of experimental and human tumors and to judge whether apparently
      recurrent tumors which appear after therapeutic treatment are truly due to
      recurrence or due to new induction of a second tumor. Results show that the
      majority of experimental and human tumors, including benign tumors, are
      monoclonal and that the majority of apparently recurrent tumors are due to true
      recurrence. A series of experimental studies on this topic are reviewed.

PMID- 15162060
TI  - Chromosomal mutagen sensitivity associated with mutations in BRCA genes.
AB  - Chromosomal mutagen sensitivity is a common feature of cells from patients with
      different kinds of cancer. A portion of breast cancer patients also shows an
      elevated sensitivity to the induction of chromosome damage in cells exposed to
      ionizing radiation or chemical mutagens. Segregation analysis in families of
      patients with breast cancer indicated heritability of mutagen sensitivity. It has
      therefore been suggested that mutations in low-penetrance genes which are
      possibly involved in DNA repair predispose a substantial portion of breast cancer
      patients. Chromosomal mutagen sensitivity has been determined with the G2
      chromosome aberration test and the G(0) micronucleus test (MNT). However, there
      seems to be no clear correlation between the results from the two tests,
      indicating that the inherited defect leading to enhanced G(0) sensitivity is
      different from that causing G2 sensitivity. Less than 5% of breast cancer
      patients have a familial form of the disease due to inherited mutations in the
      breast cancer susceptibility genes BRCA1 or BRCA2. Heterozygous mutations in
      BRCA1 or BRCA2 in lymphocytes from women with familial breast cancer are also
      associated with mutagen sensitivity. Differentiation between mutation carriers
      and controls seems to be much better with the MNT than with the G2 assay. Mutagen
      sensitivity was detected with the MNT not only after irradiation but also after
      treatment with chemical mutagens including various cytostatics. The enhanced
      formation of micronuclei after exposure of lymphocytes to these substances
      suggests that different DNA repair pathways are affected by a BRCA1 mutation in
      accordance with the proposed central role of BRCA1 in maintaining genomic
      integrity. Mutations in BRCA1 and BRCA2 seem to predispose cells to an increased
      risk of mutagenesis and transformation after exposure to radiation or
      cytostatics. This raises a question about potentially increased risks by
      mammography and cancer therapy in women carrying a mutation in one of the BRCA
      genes. Lymphoblastoid cell lines (LCLs) from breast cancer patients have been
      used to study the mechanisms and genetic changes associated with tumorigenesis.
      With respect to mutagen sensitivity, conflicting results have been reported. In
      particular enhanced induction of micronuclei does not seem to be a general
      feature of LCLs with a BRCA1 mutation in contrast to lymphocytes with the same
      mutation. Therefore, LCLs are of limited utility for studying the mechanisms
      underlying chromosomal mutagen sensitivity.

PMID- 15162061
TI  - Possible causes of chromosome instability: comparison of chromosomal
      abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1.
AB  - A large proportion of epithelial cancers show the chromosome-instability
      phenotype, in which they have many chromosome abnormalities. This is thought to
      be the result of mutations that disrupt chromosome maintenance, but the causative
      mutations are not known. We identified cell lines known to have mutations that
      might cause chromosome instability, and examined their karyotypes. Two cell
      lines, the breast cancer line HCC1937 and the pancreatic cancer line CAPAN-1,
      that have mutations respectively in BRCA1 and BRCA2, had very abnormal
      karyotypes, with many structural and numerical chromosome changes and substantial
      variation between metaphases. However, two colorectal cancer lines with mutations
      in BUB1, a spindle checkpoint protein involved in chromosome segregation, had
      rather simple near-tetraploid karyotypes, with minimal loss or gain of
      chromosomes other than the endoreduplication event, and minimal structural
      change. Apart from tetraploidy, these karyotypes were typical of colorectal lines
      considered to be chromosomally stable. Two lines derived from the same tumour,
      DLD-1 and HCT-15, with bi-allelic mutation of CHK2, had karyotypes that were
      typical of near-diploid colorectal lines considered chromosomally stable. The
      karyotypes observed supported the proposed role for BRCA1 and BRCA2 mutations in
      chromosomal instability, but showed that the tested mutations in BUB1 and CHK2
      did not result in karyotypes that would have been predicted if they were
      sufficient for chromosomal instability.

PMID- 15162062
TI  - Quantitative PCR analysis reveals a high incidence of large intragenic deletions
      in the FANCA gene in Spanish Fanconi anemia patients.
AB  - Fanconi anaemia is an autosomal recessive disease characterized by chromosome
      fragility, multiple congenital abnormalities, progressive bone marrow failure and
      a high predisposition to develop malignancies. Most of the Fanconi anaemia
      patients belong to complementation group FA-A due to mutations in the FANCA gene.
      This gene contains 43 exons along a 4.3-kb coding sequence with a very
      heterogeneous mutational spectrum that makes the mutation screening of FANCA a
      difficult task. In addition, as the FANCA gene is rich in Alu sequences, it was
      reported that Alu-mediated recombination led to large intragenic deletions that
      cannot be detected in heterozygous state by conventional PCR, SSCP analysis, or
      DNA sequencing. To overcome this problem, a method based on quantitative
      fluorescent multiplex PCR was proposed to detect intragenic deletions in FANCA
      involving the most frequently deleted exons (exons 5, 11, 17, 21 and 31). Here we
      apply the proposed method to detect intragenic deletions in 25 Spanish FA-A
      patients previously assigned to complementation group FA-A by FANCA cDNA
      retroviral transduction. A total of eight heterozygous deletions involving from
      one to more than 26 exons were detected. Thus, one third of the patients carried
      a large intragenic deletion that would have not been detected by conventional
      methods. These results are in agreement with previously published data and
      indicate that large intragenic deletions are one of the most frequent mutations
      leading to Fanconi anaemia. Consequently, this technology should be applied in
      future studies on FANCA to improve the mutation detection rate.

PMID- 15162063
TI  - Analysis of ETV6/RUNX1 fusions for evaluating the late effects of cancer therapy
      in ALL (acute lymphoblastic leukemia) cured patients.
AB  - Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in childhood.
      The improvements of therapies have increased the number of long-term survivors.
      However, an increased incidence of secondary neoplasias has been observed in this
      cohort. Our purpose was to evaluate the late effects of cancer therapy in cured
      patients previously treated for ALL, considering previous reports on the
      occurrence of gene fusions as putative markers of chromosomal instability. Twelve
      ALL patients (aged 5 to 16 years) and twelve healthy subjects (aged 18 to 22
      years) were studied for the presence of ETV6/RUNX1 (TEL/AML1) translocations,
      which were detected by FISH (fluorescence in situ hybridization). The blood
      samples were collected months or years after completion of the therapy, and the
      frequencies of gene fusions in lymphocytes were compared with those obtained
      retrospectively for bone marrow samples at the time of diagnosis, and also for
      the control group. It was demonstrated that ETV6/RUNX1 gene fusion was a frequent
      event (0.59-1.84/100 cells) in peripheral blood lymphocytes from normal
      individuals and the ALL patients who underwent chemotherapy showed significantly
      (P = 0.0043) increased frequencies (0.62-3.96/100 cells) of the rearrangement
      when compared with the control groups (patients at diagnosis and healthy
      subjects). However, a significant difference was not found between the groups of
      patients at diagnosis and healthy subjects, when the two patients who were
      positive for the rearrangement were excluded. Therefore, increased frequencies of
      ETV6/RUNX1 fusions in ALL cured patients indicate the influence of previous
      exposure to anti-cancer drugs, and they may represent an important genetic marker
      for estimating the risk of relapse, or development of secondary neoplasias.

PMID- 15162064
TI  - Comparative genomic hybridization (CGH): ten years of substantial progress in
      human solid tumor molecular cytogenetics.
AB  - Data from ten years of research using comparative genomic hybridization (CGH) for
      the detection of chromosomal alterations in human solid tumors are concisely
      reviewed. By use of a basic methodology with some variations more or less
      specific patterns of genomic imbalances were found in a large number of tumors of
      various entities. Specific gains and losses of genomic material have not only
      opened the way to the detection of a series of cancer-related genes but also to
      clinical implications. Not only several areas of basic oncogenetic research, but
      also differential diagnosis, prognosis of disease progression, and therapeutic
      decisions have profited by CGH.

PMID- 15162065
TI  - Chromosomal aberrations in arsenic-exposed human populations: a review with
      special reference to a comprehensive study in West Bengal, India.
AB  - For centuries arsenic has played an important role in science, technology, and
      medicine. Arsenic for its environmental pervasiveness has gained unexpected
      entrance to the human body through food, water and air, thereby posing a great
      threat to public health due to its toxic effect and carcinogenicity. Thus, in
      modern scenario arsenic is synonymous with "toxic" and is documented as a
      paradoxical human carcinogen, although its mechanism of induction of neoplasia
      remains elusive. To assess the risk from environmental and occupational exposure
      of arsenic, in vivo cytogenetic assays have been conducted in arseniasis-endemic
      areas of the world using chromosomal aberrations (CA) and sister chromatid
      exchanges (SCE) as biomarkers in peripheral blood lymphocytes. The primary aim of
      this report is to critically review and update the existing in vivo cytogenetic
      studies performed on arsenic-exposed populations around the world and compare the
      results on CA and SCE from our own study, conducted in arsenic-endemic villages
      of North 24 Parganas (district) of West Bengal, India from 1999 to 2003. Based on
      a structured questionnaire, 165 symptomatic (having arsenic induced skin lesions)
      subjects were selected as the exposed cases consuming water having a mean arsenic
      content of 214.96 microg/l. For comparison 155 age-sex matched control subjects
      from an unaffected district (Midnapur) of West Bengal were recruited. Similar to
      other arsenic exposed populations our population also showed a significant
      difference (P < 0.01) in the frequencies of CA and SCE between the cases and
      control group. Presence of substantial chromosome damage in lymphocytes in the
      exposed population predicts an increased future carcinogenic risk by this
      metalloid.

PMID- 15162066
TI  - Chromosomal radiosensitivity and low penetrance predisposition to cancer.
AB  - This mini-review summarises studies in this Institute on the sensitivity of cells
      of patients with common cancers to the chromosome-damaging effects of ionising
      radiation, in the context of related studies. Using the 90th percentile of
      healthy controls (n >200) as the cut-off point between a normal and a sensitive
      response, 40% of patients with breast cancer (n = 166) were sensitive when cells
      were irradiated in the G2 phase of the cell cycle. Smaller studies showed that
      patients with colorectal, head and neck (at < 45 years) and childhood cancers
      also exhibited degrees of enhanced sensitivity, whereas cervical and lung cancer
      cases did not. Cells from breast and head and neck cases irradiated in G(0) also
      showed increased sensitivity. We propose that such elevated sensitivity is a
      marker of low penetrance predisposition to cancer. The strongest support for this
      hypothesis was our demonstration of the Mendelian heritability of chromosomal
      radiosensitivity in 95 family members of breast cancer cases. Challenges for the
      future include more heritability studies, identification of the underlying
      genetic determinants, assessment of the associated cancer risk (spontaneous and
      radiogenic) and population screening for cancer prevention strategies.

PMID- 15162067
TI  - Cytogenetic studies in mice treated with the jet fuels, Jet-A and JP-8.
AB  - The genotoxic potential of the jet fuels, Jet-A and JP-8, were examined in mice
      treated on the skin with a single dose of 240 mg/mouse. Peripheral blood smears
      were prepared at the start of the experiment (t = 0), and at 24, 48 and 72 h
      following treatment with jet fuels. Femoral bone marrow smears were made when all
      animals were sacrificed at 72 h. In both tissues, the extent of genotoxicity was
      determined from the incidence of micronuclei (MN) in polychromatic erythrocytes.
      The frequency of MN in the peripheral blood of mice treated with Jet-A and JP-8
      increased over time and reached statistical significance at 72 h, as compared
      with concurrent control animals. The incidence of MN was also higher in bone
      marrow cells of mice exposed to Jet-A and JP-8 as compared with controls. Thus,
      at the dose tested, a small but significant genotoxic effect of jet fuels was
      observed in the blood and bone marrow cells of mice treated on the skin.

PMID- 15162068
TI  - Chromosomal aberrations and risk of cancer in humans: an epidemiologic
      perspective.
AB  - The pioneering papers published more than one century ago by Theodor Boveri
      opened the way to extensive research on the mechanism linking chromosomal
      abnormalities to the pathogenesis of cancer. As a result of this effort, robust
      theoretical and empirical evidence correlating cytogenetic damage to early stages
      of cancer in humans was consolidated, and an increased cancer risk was postulated
      in healthy subjects with high levels of chromosomal aberrations (CA). The first
      epidemiological investigation aimed at validating CA as predictor of cancer risk
      was carried out in the early 1990s. In that report the Nordic Study Group
      described an 80% increased risk of cancer in healthy subjects with high
      frequencies of CA. The results of this first study were replicated a few years
      later in a parallel research initiative carried out in Italy, and the subsequent
      pooled analysis of these two cohorts published in 1998 contributed to refine the
      quantitative estimate of the CA/cancer association. A small case-control study
      nested in a cohort of subjects screened for CA in Taiwan found an increased risk
      in subjects with high frequency of chromosome-type CA, while in 2001 a
      significant increase of cancer incidence associated with high levels of CA was
      described in a new independent cohort of radon exposed workers from the Czech
      Republic. Despite some common limitations affecting study design, the studies
      cited above have provided results of great interest both for the understanding of
      mechanisms of early stages of carcinogenesis, and for their potential implication
      for cancer prevention. The recent evolution of molecular techniques and the
      refinement of high throughput techniques have the potential to improve the
      knowledge about the role of specific sub-types of CA and to provide further
      insight into the mechanisms. Finally, the most challenging perspective in the
      field is the passage from research to regulation, with the implementation of
      preventive policies based on the accumulated knowledge.

PMID- 15162070
TI  - mBAND: a high resolution multicolor banding technique for the detection of
      complex intrachromosomal aberrations.
AB  - Precise breakpoint definition of chromosomal rearrangements using conventional
      banding techniques often fails, especially when more than two breakpoints are
      involved. The classic banding procedure results in a pattern of alternating light
      and dark bands. Hence, in banded chromosomes a specific chromosomal band is
      rather identified by the surrounding banding pattern than by its own specific
      morphology. In chromosomal rearrangements the original pattern is altered and
      therefore the unequivocal determination of breakpoints is not obvious. The
      multicolor banding technique (mBAND, see Chudoba et al., 1999) is able to
      identify breakpoints unambiguously, even in highly complex chromosomal
      aberrations. The mBAND technique is presented and illustrated in a case of
      intrachromosomal rearrangement with seven breakpoints all having occurred on one
      chromosome 16, emphasizing the unique analyzing power of mBAND as compared to
      conventional banding techniques.

PMID- 15162069
TI  - New developments in automated cytogenetic imaging: unattended scoring of
      dicentric chromosomes, micronuclei, single cell gel electrophoresis, and
      fluorescence signals.
AB  - The quantification of DNA damage, both in vivo and in vitro, can be very time
      consuming, since large amounts of samples need to be scored. Additional
      uncertainties may arise due to the lack of documentation or by scoring biases.
      Image analysis automation is a possible strategy to cope with these difficulties
      and to generate a new quality of reproducibility. In this communication we
      collected some recent results obtained with the automated scanning platform
      Metafer, covering applications that are being used in radiation research,
      biological dosimetry, DNA repair research and environmental mutagenesis studies.
      We can show that the automated scoring for dicentric chromosomes, for
      micronuclei, and for Comet assay cells produce reliable and reproducible results,
      which prove the usability of automated scanning in the above mentioned research
      fields.

PMID- 15162071
TI  - Nitric Oxide synthase (NOS) does not contribute to simulated ischaemic
      preconditioning in an isolated rat cardiomyocyte model.
AB  - It is widely accepted that nitric oxide (NO) is a trigger and mediator of late
      ischaemic preconditioning (IP), however its role in classic (protection observed
      within 2-4 hours after the IP stimulus) IP is less certain. In addition, the
      contribution of cardiomyocyte nitric oxide synthase (NOS) activation to NO
      production in ischaemia is unknown. The aim of this study was therefore to
      investigate the role of NOS, NO, reactive oxygen species (ROS) and cGMP in IP in
      an isolated cardiomyocyte model. METHODS: Adult rat cardiomyocytes were isolated
      by collagenase perfusion. Hypoxia was induced by covering pelleted cardiomyocytes
      with mineral oil. The IP protocol was one 10 min hypoxia/20 min reoxygenation
      cycle, followed by 2 hr sustained hypoxia. Non-IP cells were subjected to 2 hr
      sustained hypoxia only. The contribution of NO was investigated by NOS inhibition
      (L-NAME 50 microM) or by pre-treatment of cells with a NO donor (SNP 100 microM),
      and that of ROS by inclusion of ROS scavengers (MPG and N-acetyl-cysteine) or pre
      treatment with H(2)O(2). End-points were cellular cGMP content and cell viability
      as assessed by trypan blue exclusion (TBE) and cell morphology. RESULTS: IP
      significantly improved myocyte viability (54% increase in TBE) at the end of
      sustained hypoxia. Treatment of cells with L-NAME and ROS scavengers during
      either the IP protocol or during sustained hypoxia had no effect on cell
      viability after 2 hr hypoxia, whereas viability of non-IP cells treated with L
      NAME during sustained hypoxia improved significantly. cGMP levels were reduced in
      IP cells. Pre-treatment with SNP and H(2)O(2) did not mimic IP. CONCLUSIONS: IP
      conferred cardioprotection in isolated cardiomyocytes. Protection in this model
      was not due to activation of cardiomyocyte NOS or ROS production. However, NOS
      activation induced by sustained hypoxia, appeared to be harmful to non-IP cells.

PMID- 15162072
TI  - Myocardial protection from either ischaemic preconditioning or nicorandil is not
      blocked by gliclazide.
AB  - OBJECTIVE: We compared the effects of two sulphonylureas, glibenclamide and
      gliclazide, on ischaemic preconditioning (IPC) and nicorandil-induced protection
      in the in-vivo rat. We also studied the effects of these agents on the membrane
      potential of isolated rat mitochondria. METHODS: Anaesthetised male Sprague
      Dawley rats were used in an open chest model of myocardial infarction. Animals
      were randomly assigned to receive one of the following drugs: (1) saline control,
      (2) glibenclamide, 0.3 mg/kg, or (3) gliclazide, 1 mg/kg i.v. bolus. Each was
      then further randomised to one of the following treatments: (a) control, (b) IPC
      (consisting of 2 x 5 mins of regional ischaemia and 5 minutes reperfusion) or (c)
      nicorandil (50 ug/kg/min i.v). infusion. Each group then underwent 25 mins
      regional ischaemia and 2 hrs reperfusion. Infarct to risk zone ratio (%) was
      calculated by computerised planimetry of tetrazolium stained heart slices. The
      membrane potential of mitochondria isolated from rat ventricles was measured
      using flow cytometry. Comparisons were made between groups in control medium,
      nicorandil alone, and nicorandil with either glibenclamide or gliclazide.
      RESULTS: Infarct size was significantly reduced with IPC (15.0 +/- 1.1%,) and
      nicorandil (25.5 +/- 4.2%), versus control (44.1 +/- 3.2%), p < 0.005.
      Glibenclamide abolished IPC (40.8 +/- 4.6%) and nicorandil-induced protection
      completely (39.5 +/- 5.1%). Gliclazide had no adverse effect on IPC (20.4 +/-
      1.9%) or nicorandil-induced protection (23.6 +/- 2.2%), p < 0.005. Nicorandil
      caused a partial depolarisation of the mitochondrial membrane potential (-14.92
      +/- 2.34%), which was abolished by glibenclamide (+2.03 +/- 0.53%), but not
      gliclazide (-16.47 +/- 3.36%), p < 0.01. CONCLUSION: Both IPC and nicorandil
      induced protection are abolished by glibenclamide but not gliclazide in-vivo.
      These results may have important clinical implications in type II diabetic
      patients at risk of acute coronary syndromes.

PMID- 15162073
TI  - Acetaminophen and experimental acute myocardial infarction.
AB  - Acetaminophen is a widely used analgesic, and recent studies have shown that it
      has some benefits in the ischemic heart. The purpose of this study was to test
      the effects of acetaminophen on infarct size, regional myocardial blood flow and
      the "no-reflow" phenomenon in a rabbit model of coronary artery occlusion (CAO)
      and reperfusion. Rabbits were assigned to one of four groups: (1) acetaminophen,
      75 mg/kg in 75% ethanol, 30 min before CAO, (2) vehicle at 30 min before CAO, (3)
      acetaminophen at 18 min after CAO (12 min before reperfusion), or (4) vehicle at
      18 min of CAO ( n = 10 each group). All rabbits received 30 min of CAO followed
      by 3 hr reperfusion. The extent of ischemia was similar in all groups comprising
      24-27% of the left ventricle. Infarct size (% ischemic zone) was 51 +/- 5, 56 +/-
      3 in groups 1 and 2 ( p = ns), 43 +/- 3 and 40 +/- 4 in groups 3 and 4 ( p = ns).
      Thus acetaminophen did not affect the development of necrosis. Heart rate and
      blood pressure were unchanged by acetaminophen treatment. Regional myocardial
      blood flow was similar in all groups during occlusion and at the end of
      reperfusion. Acetaminophen had no effect on the size of the anatomic zone of no
      reflow that developed by 3 hours of reperfusion. We conclude that acetaminophen
      has a neutral effect in this experimental model of ischemia/reperfusion and
      appears to be safe in the course of experimental myocardial infarction.

PMID- 15162074
TI  - Omapatrilat limits infarct size and lowers the threshold for induction of
      myocardial preconditioning through a bradykinin receptor-mediated mechanism.
AB  - Bradykinin is an important endogenous trigger of myocardial ischemic
      preconditioning (IPC). Through simultaneous inhibition of neutral endopeptidase
      and angiotensin converting enzyme, omapatrilat prevents enzymatic degradation of
      bradykinin. The aim of this study was to investigate if omapatrilat, through its
      ability to augment bradykinin levels, can augment a subthreshold IPC stimulus
      (Sub-IPC) and to compare the action of omapatrilat with the angiotensin
      converting enzyme inhibitor, captopril. Langendorff perfused rat hearts were
      subjected to 35 min left coronary artery occlusion and 120 min reperfusion. Full
      IPC was induced with 5 min global ischemia/10 min reperfusion and substantially
      limited infarct size (21.5 +/- 3.5% of risk zone vs 53.4 +/- 2.0% in controls, P
      < 0.01). Sub-IPC (2 min global ischemia/10 min reperfusion) did not limit infarct
      size (48.4 +/- 3.8%). Omapatrilat (10 micromol/L) or captopril (200 micromol/L)
      were administered alone or in conjunction with Sub-IPC. Reduced infarct size
      comparable to that observed with the full IPC protocol was seen when sub-IPC was
      combined with either omapatrilat (19.7 +/- 2.5%) or captopril (20.3 +/- 4.9%).
      Omapatrilat alone caused modest reduction of infarct size (34.6 +/- 1.5%, P <
      0.01 v control), an effect not observed with captopril. Hoe140, a selective kinin
      B(2) receptor antagonist, eliminated the cardioprotective effect of omaptrilat
      alone or in combination with sub-IPC. We conclude that omapatrilat elicits
      cardioprotection via inhibition of bradykinin degradation and that dual
      inhibition of angiotensin-converting enzyme and neutral endopeptidase may have
      beneficial effects beyond standard angiotensin-converting enzyme inhibitor
      therapy in patients with acute coronary syndromes who are at risk of myocardial
      infarction.

PMID- 15162075
TI  - Different effects of exercise on plasma concentrations of nebivolol, bisoprolol
      and carvedilol.
AB  - BACKGROUND: In-vitro studies have shown that beta-blockers are taken up into and
      released from adrenergic cells together with epinephrine and norepinephrine.
      Consequently, studies in humans revealed an increase in plasma concentrations of
      propranolol and atenolol, whereas those of carvedilol were not affected by
      physical exercise. However, nebivolol and bisoprolol never were investigated on
      this issue. METHODS: Ten healthy males received oral doses of 5 mg nebivolol, 5
      mg bisoprolol, and 50 mg carvedilol daily for one week in a cross-over fashion.
      Exercise was performed at 3 hours following oral intake of the respective last
      drugs on the eighth day. Blood samples were taken at rest, during the last minute
      of exercise, and after 15 min of recovery. RESULTS: At rest and during exercise,
      heart rates were as follows: Nebivolol, 57 +/- 7 and 137 +/- 11 beats/min;
      bisoprolol, 55 +/- 5 and 139 +/- 14 beats/min; carvedilol, 56 +/- 5 and 135 +/-
      13 beats/min, with no significant differences between the drugs. Plasma
      concentrations were as follows: Nebivolol-rest 0.273 +/- 0.029 ng/ml, exercise
      0.274 +/- 0.035 ng/ml, recovery 0.272 +/- 0.035 ng/ml (n.s.). Bisoprolol-rest
      4.99 +/- 2.73 ng/ml, exercise 6.49 +/- 5.58 ng/ml, recovery 4.90 +/- 3.06 ng/ml (
      p < 0.01). Carvedilol-rest 10.3 +/- 9.3 ng/ml, exercise 9.7 +/- 8.2 ng/ml,
      recovery 6.5 +/- 5.6 ng/ml ( p < 0.05). DISCUSSION: Plasma concentrations of
      bisoprolol increased during exercise and returned to baseline during recovery, a
      behaviour which would have been predicted according to present knowledge.
      However, exercise had no effect on plasma concentrations of nebivolol and
      carvedilol, a finding that is in contrast to previous results with other beta
      blockers such as propranolol and atenolol. We conclude that both nebivolol and
      carvedilol are not taken up into and released from adrenergic nerves during
      exercise, a feature that clearly distinguishes these drugs from other beta
      blockers so far investigated.

PMID- 15162076
TI  - A description of the clinical characteristics at baseline of patients recruited
      into the Carvedilol or Metoprolol European Trial (COMET).
AB  - BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised
      trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with
      metoprolol, a beta-1-selective agent in patients with heart failure and left
      ventricular systolic dysfunction. The trial showed a reduction in mortality with
      carvedilol that was consistent across subgroups. The purpose of this report is to
      describe in greater detail the heterogeneity of this population at baseline with
      particular reference to the impact of symptomatic severity, age and gender on
      patient characteristics. METHODS: A descriptive report using data entered in the
      COMET study data-base. RESULTS: The characteristics of the population studied
      were similar to those reported in previous trials of beta-blockers. Almost all
      patients were receiving diuretics and ACE inhibitors with few patients taking
      angiotensin receptor blockers. As expected, older patients had more co-morbidity.
      Older patients and women reported worse symptoms and poorer well-being despite
      similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in
      patients with more severe symptoms and older patients but not in women, although
      differences in NT-proBNP may have been confounded by differences in renal
      function. CONCLUSION: Age and gender, as well as the severity of cardiac
      dysfunction, appear to have an important effect on the severity of heart failure
      symptoms and patient 'well-being'. This could have important implications for the
      relationship between symptoms and prognosis and therefore the way in which
      patients are selected for clinical trials and the goals of treatment. This will
      be the subject of further analyses.

PMID- 15162077
TI  - Increasing awareness and perception of heart failure in Europe and improving care
      -rationale and design of the SHAPE Study.
AB  - In the last decennia heart failure has become one of the most important diseases
      worldwide in terms of prevalence, morbidity, life expectancy, and in health care
      management and costs. Despite significant improvements in prevention and
      treatment, heart failure remains a frequently occurring disorder with increasing
      incidence and a high hospitalisation and death rate. As major health care problem
      it deserves full attention of health care authorities. Unfortunately, the
      seriousness of heart failure and the therapeutic possibilities are often not
      recognised by those directly involved, i.e. the doctor, the patient or his
      relatives, let alone that they are known to the general public and health care
      authorities. The SHAPE study aims at improving heart failure care by increasing
      awareness and perception of the disease in Europe. Firstly, awareness and
      perception of heart failure will be documented in the general public, primary
      care physicians and specialists (cardiologists, internists and geriatricians) in
      9 European countries: France, Germany, Italy, the Netherlands, Poland, Romania,
      Spain, Sweden and the UK. Subsequently, the results will be used to design and
      carry out suitable awareness and educational programmes in these groups, aimed at
      improving heart failure care and research. Finally, the results of these
      programmes will be tested in a second documentation phase and adaptations made
      where needed. This manuscript describes the rationale and design of the first
      phase, the Documentation Phase.During the first documentation phase, 800
      participants per country selected based on sex, two age groups and urban vs.
      rural location (100/cell) will be surveyed using a 32-question interview.
      Questions for the general public focus on recognition, incidence and prevalence,
      severity and prognosis of the disease in comparison to other disease areas, like
      cancer, on quality of life, therapeutic possibilities and availability of care.
      The primary care physician (PCP) survey aims at receiving a minimum of 300
      responses. A questionnaire with 33 closed questions will be used covering the
      PCP's knowledge of heart failure, including prevalence, aetiology, new diagnostic
      and therapeutic developments and health care costs. Questions concerning
      diagnostic procedures and various treatments carried out by the PCP in his own
      practice, as well as referral patterns for diagnostic procedures and for
      specialist care. Questions relating to the type of practice and number of
      patients in each PCP's clinical practice. A minimum of 150 cardiologists and 150
      internists + geriatricians will be surveyed per country. The specialist's
      questionnaire contains 31 questions focusing on identification of heart failure
      patients, patients at risk, use and availability of diagnostic tools, importance
      of therapies and order of treatment, perceived risks of treatment, relevance of
      counselling and advice, use of paramedical personnel, and questions concerning
      practice size, type of practice and number of patients with heart failure.
      CONCLUSION: This first part of the SHAPE study will provide important information
      about the level of knowledge and understanding of heart failure of the general
      public, as well as the perception of the relevance of heart failure and
      appropriate diagnostic and therapeutic approaches by both the primary care
      physician and the medical specialist. This knowledge will be extremely valuable
      when it comes to defining optimal educational programmes in the different target
      groups studied in SHAPE necessary to implement appropriate heart failure care in
      Europe and to obtain the means to do so.

PMID- 15162078
TI  - Cost-effectiveness of primary implanted cardioverter defibrillator for sudden
      death prevention in congestive heart failure.
AB  - BACKGROUND: Implanted cardioverter defibrillator (ICD) is expensive but highly
      effective in preventing sudden death. The value of primary prophylactic ICD in
      preventing sudden death for congestive heart failure patients (CHF) has not been
      established. OBJECTIVE: To compare the cost-effectiveness of primary prophylactic
      ICD vs. standard drug therapy for preventing CHF sudden death. DESIGN:
      Incremental Cost per Quality-Adjusted Life Year (QALY) using a lifetime decision
      model. DATA SOURCES: Estimates of cost, utility and probabilities from
      literature, clinical experts, CMS fee schedule payments, and the Bureau of Labor
      Statistics. TARGET POPULATION: U.S. CHF patients with NYHA functional Class II
      and III. TIME HORIZON: Lifetime; future values discounted at 3%. PERSPECTIVE:
      Societal. RESULTS OF BASE-CASE ANALYSIS: In 2002 prices the discounted lifetime
      cost is 122,947 dollars with primary prophylactic ICD and 25,223 dollars without
      ICD; the QALYs gained were 2.9031 and 1.9045 respectively. The incremental cost
      effectiveness ratio was 97,861 dollars per QALY saved with prophylactic ICD.
      RESULTS OF SENSITIVITY ANALYSIS: ICD is not cost-effective under plausible
      scenarios using 50,000-80,000 dollars per QALY as the cost effectiveness
      threshold. The cost-effectiveness ratio is quite sensitive to patient utility
      after ICD implantation, and the proportion of CHF patients experiencing sudden
      death. CONCLUSIONS: Using a standard cost-effectiveness threshold and plausible
      parameter ranges, it is unlikely that ICD is cost-effectiveness in preventing CHF
      sudden death relative to standard drug therapy.

PMID- 15162079
TI  - When street sex workers are mothers.
AB  - Many women who engage in street sex work experience pregnancies and become
      mothers. Unfortunately, little research has examined how their pregnancies and
      parenting impact themselves as street sex workers and their street sex work. In
      this qualitative research study, 16 mothers who were currently involved in street
      sex work in a Midwestern city of the United States participated in semistructured
      interviews. These mothers discussed how being pregnant or parenting while
      regularly working the street caused them to feel ashamed of themselves and their
      work and anxious for their own and their children's safety. Pregnancies and
      parenting responsibilities reportedly altered their working productivity and
      practices. Given how frequently they had been separated from their children, they
      also talked about ways in which these separations resulted in them having more
      free time and need for drugs, which led to them increasing the amount they worked
      the street. It is evident from these interviews that street sex workers who are
      mothers have unique needs and experiences that must be considered by researchers,
      policy makers, and service providers.

PMID- 15162081
TI  - Who pays for sex and why? An analysis of social and motivational factors
      associated with male clients of sex workers.
AB  - A total of 1,225 men and women attending a commercial event in the state of
      Victoria, Australia were surveyed as to whether they had ever paid for sex. Of
      612 men surveyed, 143 (23.4%) had paid for sex at least once. Men who had ever
      paid for sex were compared with male nonclients on 13 demographic and sexual
      history measures; only four significantly differentiated clients from nonclients.
      Clients were significantly older, less likely to have been educated beyond high
      school, less likely to report having a regular partner in the past 6 months, and
      more likely to report that their most recent sexual encounter was with a casual
      partner. Clients of sex workers reported the major reason for paying for sex was
      to satisfy their sexual needs (43.8%), followed by the belief that paying for sex
      was less trouble (36.4%), and that it would be entertaining (35.5%). A factor
      analysis of reasons for visiting sex workers identified three factors labelled
      Ease, Engagement, and Arousal. Together, these factors accounted for 55% of the
      variance associated with the factor solution of motivations for paying for sex.
      In a setting where commercial sex is legally available from brothels, it would
      appear that clients are unremarkable in their social characteristics and are
      motivated mainly by the ease of the commercial sex encounter, the need for
      engagement with another, and because they feel in need of sexual "relief."

PMID- 15162080
TI  - A qualitative exploration of female sex work in Tijuana, Mexico.
AB  - Previous research has documented high rates of STDs and increased risk of HIV
      infection among female sex workers (FSWs) in Mexico; however, little is known
      about the sexual risk behaviors of this population. The purpose of this study was
      to explore work history, context of sex work, sexual risk practices, client
      characteristics, attitudes toward condoms, and potential barriers to condom use
      in a sample of FSWs in Tijuana, Mexico. Analysis of qualitative data from 25 FSWs
      revealed that most women entered the sex trade at a young age ( M = 23 years),
      primarily as a result of financial need. Forty percent were single mothers
      supporting children. Women worked an average of 6-7 days per week; work shifts
      ranged from 4 to 13 hr per day. Clients were both Mexican and foreign (mostly
      American and Asian), and ranged in age from 18 to 80 years. Positive aspects of
      the job included flexible work hours and good income. Negative aspects of sex
      work included risks associated with physical assault, diseases, and unwanted
      pregnancies. Most clients did not want to use a condom and many offered
      additional money for unprotected sex. FSWs did not like to use condoms because
      they were perceived as uncomfortable. Most FSWs did not negotiate the use of
      condoms, had a low knowledge regarding the proper use of condoms, and were
      reticent to report their own unsafe sex practices. These results suggest the need
      to develop culturally appropriate safer sex interventions for FSWs in Mexican
      border cities.

PMID- 15162082
TI  - Sexual content induced delay: a reexamination investigating relation to sexual
      desire.
AB  - This article reports the utility of an information processing approach to examine
      whether there is a relationship between sexual content induced delay and levels
      of sexual desire as determined by self-report questionnaires. We tested this idea
      using a partial replication of the J. H. Geer and H. S. Bellard (1996) protocol
      demonstrating sexual content induced delay (SCID) in responding to sexual versus
      neutral words. In addition, the experiment examined whether SCID was different in
      people with varying levels of sexual desire. It was hypothesized that persons
      with low levels of sexual desire might respond more slowly to sexual word cues
      than others. Words with equal frequency of usage and similar word length were
      chosen from among those used in the Geer and Bellard study. The experiment was
      conducted with 171 volunteers who completed sexual desire questionnaires, lexical
      decision making tasks, and word ratings. The SCID effect was demonstrated by both
      men and women in the study with no significant variation between the sexes. In
      accordance with prediction, it was found that persons with lower levels of sexual
      desire responded more slowly to sexual stimuli than other participants, and rated
      sexual words as less familiar, less acceptable, and less positive emotionally to
      them. These findings have implications for understanding how emotional content
      contributes to SCID. They also suggest that further exploration of these ideas,
      perhaps using other stimulus modalities, may be helpful in advancing
      understanding of responses to sexual cues, and the potential implications that
      may have in better understanding sexual desire.

PMID- 15162083
TI  - Conscious processing of sexual information: mechanisms of appraisal.
AB  - To elucidate some of the activational mechanisms of sexual response, this study
      investigated the effects of conscious appraisal of sexual and neutral stimuli on
      a categorization task and on ratings of sexual arousal. Conscious appraisal is
      dependent on memory, regulatory, and attentional processes, interacting with one
      another. It is proposed that regulation is activated by attention, furnished by
      representations from implicit and explicit memory. Participants (26 men and 25
      women) were asked to respond to "target" stimuli that were preceded by
      supraliminal "prime" stimuli. Primes and targets were operationalized by slides
      with sexual (i.e., romantic vs. explicit) and neutral content. In a cognitive
      task, participants had to group randomly presented targets as quickly as possible
      into sexual and nonsexual categories. Categorization of sexual targets was
      delayed when they were preceded by sexual primes compared to neutral primes. This
      was interpreted as an inhibitory process and compared with the Sexual Content
      Induced Delay phenomenon (J. H. Geer & H. S. Bellard, 1996; J. H. Geer & J. S.
      Melton, 1997). No gender difference was found. In a subsequent affective task,
      participants provided an assessment of sexual arousal, followed by an evaluation
      of the target. This task was hypothesized to result in differential access to
      memory, where assessments of sexual arousal are influenced mainly by implicit
      memory, and where evaluations are influenced mainly by explicit memory. Gender
      differences were most prominent in the evaluation aspect of this task. It was
      concluded that cognitive processing of sexual information is similar for both
      genders, but that gender differences are present in affective processing of
      sexual information.

PMID- 15162084
TI  - A prospective study of intraindividual and peer influences on adolescents'
      heterosexual romantic and sexual behavior.
AB  - Theories and empirical studies of adolescent sexual behavior have identified the
      contributions of personal attributes and social experiences; however, it is rare
      that models have clarified developmental pathways to adolescent sexual behavior
      that include (1) factors assessed prior to and early in adolescence and (2)
      dyadic experiences in adolescence that provide the opportunity for sexual
      behavior (i.e., dating). Using data from a prospective study, structural equation
      modeling was used to test a model predicting adolescent sexual behavior at age
      19, denoted by the number of lifetime sexual partners. Predictors examined were
      sociability and impulsivity assessed at 30 months of age, physical
      characteristics and experiences with peers measured at age 12-13, the age of
      first romantic relationship, and frequency of alcohol use at age 16. The pathway
      to greater sexual involvement was marked by some desired personal attributes
      (e.g., sociability) and peer experiences (e.g., higher quality friendships).
      These associations were mediated, however, by earlier initiation of romantic
      relationships and more frequent use of alcohol in middle adolescence. Earlier
      initiation of romantic relationships and more frequent alcohol use were predicted
      by greater sociability and less impulsivity in childhood, higher quality
      friendships and greater peer acceptance in early adolescence, and a more mature
      appearance and physical attractiveness (among females) at age 13. The findings
      imply a complex pathway that leads to a greater accumulation of sexual partners
      by age 19. This pathway begins in childhood and includes individual qualities,
      peer acceptance, romantic relationships, and alcohol use.

PMID- 15162085
TI  - Gender differences in affective responses to sexual rejection.
AB  - The aim of this study was to answer the following questions: (1) Are affective
      responses to sexual rejection different for men and women? (2) Do positive
      emotions to sexual rejection occur and how do they balance with negative
      emotions? (3) How can gender differences in affective responses to sexual
      rejection be explained? A sample of 67 men and 65 women (age 18-30 years)
      completed a questionnaire in which they rated their affective responses to a
      hypothetical situation of sexual rejection. Analyses of variance revealed gender
      differences: men anticipated a less negative and more positive affective response
      to sexual rejection than women did. Men also reported they would experience a
      more positive than negative affective response after supposedly being sexually
      rejected. Hierarchical multiple regression analyses showed that differences
      between men and women were mediated by the respondents' expectations in the
      stimulus situation, their interest in casual sex, and their masculinity.

PMID- 15162087
TI  - Stroke where you least expect it.

PMID- 15162086
TI  - Sex differences in sexual psychology produce sex-similar preferences for a short
      term mate.
AB  - We explored aspects of men's and women's short-term sexual psychology as a
      function of a potential short-term partner's relationship status. A total of 209
      men and 288 women reported how likely they would be to pursue a casual sexual
      relationship with an attractive member of the opposite sex who was (1) married,
      (2) not married but has casual sexual partners, or (3) not married and has no
      casual sexual partners. Guided by sperm competition theory, we predicted and
      found that men prefer short-term sex partners who are not already involved in
      relationships and hence present a relatively low risk of sperm competition.
      Because women sometimes use short-term sexual relationships to acquire long-term
      partners, we predicted and found that women prefer short-term sexual partners who
      are not already involved in relationships and hence present relatively greater
      promise as a potential long-term partner. Finally, across each of the three
      levels of the imagined partner's relationship status, men reported a greater
      likelihood than did women of pursuing a casual sexual relationship. Discussion
      addressed methodological limitations and directions for future work.

PMID- 15162088
TI  - Risk factors for arterial ischemic stroke in childhood.
AB  - Stroke affects up to 13 of 100,000 children, is more common in boys and African
      Americans, and is associated with considerable cognitive and psychiatric
      morbidity, as well as motor disability. Around half are hemorrhagic and half are
      ischemic. Underlying conditions include sickle cell disease, cardiac
      abnormalities, chromosomal abnormalities (eg, Down syndrome), and neurocutaneous
      conditions (eg, neurofibromatosis), but up to half the patients with ischemic
      stroke have no previously diagnosed condition. Although there is almost certainly
      an important genetic component to stroke risk, head trauma, infections, drugs and
      radiation appear to play an etiological role in some patients. The majority of
      the patients with infarction in an arterial distribution have associated
      cerebrovascular disease. Vascular pathologies include carotid or vertebrobasilar
      dissection, intracranial vasculopathy affecting the middle and anterior cerebral
      arteries, which is often transient, and moyamoya. Intermediate risk factors may
      include hypertension, hypoxia, and poor nutrition leading, for example, to iron
      deficiency and hyperhomocysteinemia. Some chronic conditions may directly
      influence the child's behavior and stroke recurrence risk, although large cohorts
      and randomized controlled trials will be needed before strategies for
      modification can be evidence-based.

PMID- 15162089
TI  - Little folk strokes: current questions.

PMID- 15162090
TI  - Decision analysis of the cost-effectiveness of repetitive transcranial magnetic
      stimulation versus electroconvulsive therapy for treatment of nonpsychotic severe
      depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new
      treatment with promise for resistant depression. OBJECTIVE: We tested the
      economic feasibility of this new method compared with electroconvulsive therapy
      (ECT). METHOD: An economic decision analysis was used to compare the costs of
      three different treatment strategies for nonpsychotic severe depression. The
      strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for
      nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted
      life years (QALYs) for the three treatment options for all nonpsychotic, severely
      depressed United States patients who would have otherwise undergone ECT. A
      sensitivity analysis was performed to test the degree of change in outcome with
      various parameter changes. RESULTS: The additional cost of using ECT alone
      compared with rTMS alone was 460,031 US dollars per quality adjusted year of life
      gained. For ECT versus rTMS-to-ECT, there was both an increased cost and a loss
      of 1,538 QALYs with ECT alone. The sensitivity analysis revealed the model to be
      robust with various parameter changes. CONCLUSION: If rTMS were to be made widely
      available clinically in the US, it would offer a substantial economic benefit
      over ECT in treating resistant depression. Using rTMS-to-ECT offers not only an
      economic advantage but also an increase in QALYs. This analysis suggests that
      rTMS would be a cost-effective treatment for depression compared with the current
      option of ECT alone.

PMID- 15162091
TI  - Social and affective impairments are important recovery after acquired stroke in
      childhood.
AB  - Despite a congenital stroke, overall intelligence at school age is generally
      within the normal range. Language acquisition problems are more prominent when
      children are younger (<5 years of age) than when they are older. They are present
      after both right and left lesions, but appear to have different features. They
      are less apparent than in the child with a developmental language disorder.
      Acquired aphasia in childhood results in subtle and often persisting deficits.
      Children with congenital strokes are at risk for behavioral and psychiatric
      problems. Those with congenital right hemisphere strokes appear to be more
      difficult infants, but there is no clear side of lesion effect in older children.
      Children with congenital right hemisphere strokes have more prominent spatial
      difficulties than their left lesion counterparts. Evaluating both the process and
      the product highlights this. Increasing the difficulty of the task often brings
      out deficits in the right lesion group even when they seemingly recovered.

PMID- 15162092
TI  - Newborn brain infarction: clinical aspects and magnetic resonance imaging.
AB  - OBJECTIVE: We describe the clinical and imaging studies of 11 full-term babies
      with neonatal stroke. We classify the neonatal non-hemorrhagic strokes as
      thrombotic, embolic, or global vascular insufficiency and determine if this
      classification is improved by adding magnetic resonance spectroscopy (MRS) and
      diffusion-weighted imaging (DWI) to conventional magnetic resonance imaging (MRI)
      and magnetic resonance angiography (MRA). METHODS: Clinically, eight of the 11
      babies presented with seizures, one with apnea, and two with lethargy.
      Conventional MRI and DWI were used to classify each infarct as being either
      borderzone or vascular distribution. The location of infarction revealed the
      presumed vascular pathophysiology. RESULTS: Infants were classified as having
      either embolic (bilateral middle cerebral artery,n=1), global ischemic (bilateral
      borderzone, n=2), or thrombotic infarction (unilateral middle cerebral artery,
      n=7; bilateral posterior cerebral arteries, n=1). DWI and MRS detected a small
      infarct better than conventional MRI in one patient. MRA showed abnormal
      intracranial arteries in three, all of who were in the thrombotic group. Even
      though MRS was more sensitive than conventional MRI in detecting
      ischemia/infarction in one patient, in another there was no detectable lactate in
      the stroke region found on conventional MRI. Clinical presentation was similar in
      global ischemia and focal infarctions, but newborn stroke was more likely to
      present with lateralizing focal motor seizures. Seizures were the most common
      presenting sign, with a paucity of other focal neurological deficits. CONCLUSION:
      MRI is the best approach to determine stroke pathophysiology. Brain infarction
      frequently presents with seizures. We speculate that the location and
      distribution of infarction might determine stroke timing, pathophysiology and
      outcome. Ongoing clinical studies will likely clarify this speculation.

PMID- 15162093
TI  - Sickle cell disease: primary stroke prevention.
AB  - Stroke is an important and common complication of sickle cell disease (SCD),
      affecting children as well as adults. Clinically evident stroke, usually brain
      infarction, is usually associated with stenosis or occlusion of the intracranial
      arteries of the Circle of Willis, sometimes with formation of moyamoya (a
      Japanese word for "hazy" or "like a puff of smoke" that describes the appearance
      of a abnormal microvasculature on angiography believed secondary to internal
      carotid artery stenosis or occlusion and the resultant extensive
      collateralization). Several types of intracranial hemorrhage are observed but
      usually in older children and adults. Cerebrovascular diseases restricted to
      small vessels may go unrecognized but is associated with cognitive and learning
      problems. Prevention of recurrent stroke has been accomplished with chronic blood
      transfusion. A primary prevention strategy for clinical stroke, based on the
      Stroke Prevention in Sickle Cell Anemia Trial, has been tested in a randomized
      clinical trial. Over 2,000 young children with SCD were screened with
      transcranial Doppler ultrasound (TCD) to detect elevated blood flow velocity
      indicative of vessel disease and high risk of future stroke. Those randomized to
      standard care (no transfusion) had a 10%/year risk of stroke, which was reduced
      >90% with chronic transfusion. This approach is the only primary stroke
      prevention strategy so far tested in SCD in a randomized controlled trial. Silent
      lesions on magnetic resonance imaging are associated with an approximately
      1.5%/year risk of clinical stroke and a trial is now starting in children with
      these lesions who do not meet Stroke Prevention in Sickle Cell Anemia Trial
      criteria for transfusion based on TCD. A controlled trial, based on intervention
      for nocturnal hypoxemia, is also underway. Hydroxyurea, bone marrow
      transplantation, antiplatelet, and antithrombotic agents may work but have not
      been tested in primary prevention in a systematic way. If early and repeated, TCD
      screening of children, as recommended by National Heart Lung and Blood Institute
      and the American Stroke Association, were implemented broadly the incidence of
      new strokes could be greatly reduced in these children.

PMID- 15162094
TI  - Health-related quality of life and its relationship to neurological outcome in
      child survivors of stroke.
AB  - BACKGROUND: Ischemic stroke during infancy and childhood has the potential to
      result in neurological impairments and affect a child's ability to function at
      home, school, and play. There are limited data on the effect of ischemic stroke
      on quality of life (QOL) of child survivors of ischemic stroke. OBJECTIVE: To
      examine parent and child perspectives on QOL and examine factors that correlate
      with reduced QOL for child survivors of stroke. METHODS: A prospective single
      center cohort design was used. Participants included children 2-18 years of age
      surviving ischemic stroke. The Pediatric Quality of Life 4.0 Generic Inventory
      Scale (PedsQL) parent proxy-report (2-18 years of age) and child self-report (5
      18 years of age) were completed by participants. Scores were compared with
      standardized normative data of healthy children and those with chronic medical
      conditions. Neurological deficits were measured with the Pediatric Stroke Outcome
      Measure, a standardized evaluation for children. The relationships between stroke
      type, neurological deficit, and health-related quality of life (HRQOL) were
      examined. RESULTS: We assessed the QOL in 84 children with arterial ischemic
      stroke and 16 with cerebral sinovenous thrombosis at a mean age of 8.4 (4.12)
      years; 4.4 (2.93) years after their stroke. Results showed that both the parent
      proxy and child self-report HRQOL scores were significantly reduced (P>.01)
      compared with normative data of healthy children. Of greatest concern for both
      parents and children was the effect of stroke on school, followed by its impact
      on emotional and social functions. In contrast to other studies, scores in
      physical domain were better than those in the psychosocial domain. Multivariate
      analysis showed that of neurological deficits after stroke was a significant
      predictor of poor HRQOL (P>.05). The children with poor neurological recovery had
      the lowest mean PedsQL scores and their QOL was significantly poorer compared
      with normative data of children with chronic health conditions (ie, diabetes,
      cancer). CONCLUSION: The PedsQL appears to be a promising assessment tool of
      HRQOL for children following stroke. Both parent and child perspectives should be
      included because of the potential for there to be significant differences in
      perspectives. Although severity of neurological outcome is a significant
      predictor of reduced HRQOL, it accounted for a small proportion of variance in
      QOL scores. Further research is required to delineate other factors that are
      significant predictors of outcome.

PMID- 15162095
TI  - Hypoxia activates matrix metalloproteinase expression and the VEGF system in
      monkey choroid-retinal endothelial cells: Involvement of cytosolic phospholipase
      A2 activity.
AB  - PURPOSE: To determine whether the gene expression of matrix metalloproteinases
      (MMPs) as well as that of the pro-angiogenic cytokine vascular endothelial growth
      factor (VEGF) and its receptors change in response to hypoxic exposure in a
      primate choroid-retinal endothelial cell line, and furthermore, whether cytosolic
      phospholipase A2 (cPLA2) plays a role in this process. METHODS: Rhesus macaque
      choroid-retinal endothelial (RF/6A) cells were incubated under hypoxic conditions
      for 1, 2, 4, or 8 h prior to RNA extraction. In some experiments cells were
      pretreated with the cPLA2 inhibitor AACOCF3 (10 microM) for 30 min prior to
      hypoxia. Changes in gene expression were determined by RT-PCR and quantified by
      real-time PCR for urokinase plasminogen activator (uPA), collagenase-1 (MMP-1),
      membrane type-1 metalloproteinase (MT1-MMP), gelatinases A and B (MMP-2, MMP-9),
      tissue inhibitor-2 (TIMP-2), VEGF and its receptors, Flt-1 (VEGFR-1), KDR (VEGFR
      2), and neuropilin-1 (NP-1). MMP-2 secreted by the cells was evaluated by
      zymography. VEGF release was measured by ELISA. In tube-formation studies,
      endothelial cells (EC) were seeded into collagen gel, exposed to hypoxia for 4 h,
      then incubated under normoxic conditions for 72 h. RESULTS: Hypoxia triggered a
      three fold increase in the gene expression of MT1-MMP, MMP-2, and TIMP-2, and a
      ten fold increase in MMP-2 levels. Moreover it also induced tube formation in EC.
      Expression of uPA, MMP-1, and MMP-9 mRNA was not detected. Pretreatment with
      AACOCF3 abolished hypoxia-induced tube formation and MT1-MMP, MMP-2, and TIMP-2
      transcription. Furthermore, hypoxia produced a significant, sustained increase in
      the gene expression and release of VEGF-165, the only VEGF-A isoform detected in
      these cells. AACOCF3 reduced the hypoxia-induced VEGF release at 8 h of hypoxia.
      VEGF receptors KDR and NP-1 were constitutively expressed in EC and up-regulated
      under hypoxic conditions. CONCLUSIONS: In monkey choroid-retinal EC, hypoxia
      selectively induces MMP-2 activity. This induction is preceded by MT1-MMP, MMP-2,
      and TIMP-2 mRNA expression, as well as that of the VEGF-165 isoform and its
      receptors KDR and NP1. These increases possibly result from hypoxia-induced
      activation of cPLA2 and subsequent release of arachidonic acid and its conversion
      to prostaglandins. These molecular changes in EC could, in part, contribute to
      the angiogenic response that occurs in the development of ischemic retinopathies
      and choroidal neovascularization.

PMID- 15162097
TI  - Identification of the promoter region of the human betaIGH3 gene.
AB  - PURPOSE: To isolate and characterize the promoter of the human betaIGH3 gene.
      METHODS: Primer extension and CapSite Hunting methods were used to determine the
      transcription start sites (TSS) of the human betaIGH3 gene. Putative
      transcription factor-binding sites and potential promoter regions were identified
      by online tools. Two clones containing 3 Kb and 1 Kb of the 5'-flanking region of
      the betaIGH3 gene were isolated and their respective promoter activities were
      characterized. Various fusion constructs of betaIGH3 promoter-luciferase reporter
      were made to transfect A549 cells. The responses of these fragments to TGF-beta1
      were also measured after being treated with TGF-beta1 at different
      concentrations. Several human and nonhuman cell lines were also transfected with
      the 1 Kb betaIGH3 promoter-reporter construct to compare the activity of the
      betaIGH3 promoter in these cells. RESULTS: The transcription start site of human
      betaIGH3 mRNA was determined to be 65 bp upstream of the ATG start codon. Both
      the 3 Kb (-3011 to -1) and 1 Kb (-1000 to -1) fragments displayed strong and
      comparable promoter activity in transfected cells. Truncation analyses in A549
      cells identified the nucleotide region from -336 to -1 as having high promoter
      activity (minimal promoter). The results also indicated that the nucleotide
      fragment from -1000 to -646 contained negative regulatory elements. Twenty ng/ml
      TGF-beta1 upregulated the activity of the 1 Kb construct, but did not upregulate
      the activity of the -336 to -1 construct, suggesting that TGF-beta1 responsive
      elements existed in the region from -1000 to -336. The 1 Kb construct universally
      demonstrated promoter activity in all cell lines tested. CONCLUSIONS: We
      identified the betaIGH3 gene promoter with a distinct regulatory pattern in the 1
      Kb region upstream of the ATG start codon. Further elucidation of the functions
      of this promoter region may facilitate understanding of betaIGH3 and its related
      corneal dystrophies.

PMID- 15162096
TI  - A novel PRPF31 splice-site mutation in a Chinese family with autosomal dominant
      retinitis pigmentosa.
AB  - PURPOSE: The autosomal dominant form of retinitis pigmentosa (ADRP) can be caused
      by mutations in 13 genes and a further locus for which the gene remains to be
      identified. This study was intended to identify mutations in a large Chinese
      pedigree with ADRP. METHODS: A genome scan was conducted in the family. The whole
      coding sequences and the intron-exon boundaries of candidate genes were amplified
      and sequenced. The reverse transcriptase polymerase chain reaction (RT-PCR) was
      performed to amplify the mutated mRNA. RESULTS: The strongest evidence of linkage
      was detected with three adjacent microsatellite markers genotyped between D19S902
      and D19S210 on chromosome 19q13.33-13.43. Within the region, a single nucleotide
      change (G>A) at position -1 of Intron 5 of PRPF31 was found. The consensus AG
      doublet of the Intron 5 splice acceptor was changed to AA. The mutation co
      segregated with the disease phenotype, suggesting that it was the disease-causing
      mutation in this family. This splicing site mutation is predicted to cause an
      erroneous splicing of Exon 6. By RT-PCR, we found the mutated nucleotide of
      Intron 5 (A) and the first nucleotide of Exon 6 (G) was regarded as a new splice
      acceptor, resulting in 1 bp deletion of the first codon of Exon 6 (GAG-to-AG) at
      the mRNA level. This change led to a frameshift and truncated protein of 196
      amino acids with 56 novel amino acids prior to a premature stop. CONCLUSIONS: A
      novel splicing mutation (IVS5-1G>A) in the pre-mRNA splicing-factor gene PRPF31
      causes retinitis pigmentosa in a large Chinese family. The mutation results in a
      truncated protein of PRPF31.

PMID- 15162100
TI  - Therapy interventions for improving joint range of motion: A systematic review.
AB  - The authors conducted a systematic review of the published evidence on
      conservative interventions for loss of upper extremity joint range of motion
      following selected musculoskeletal conditions. Several databases (Medline,
      CINAHL, PEDRO, PubMed, and Cochrane) were searched for articles that met
      inclusion criteria. Two reviewers determined abstract selection; two reviews
      performed critical appraisal of 26 articles. Level of evidence and quality on a
      24-item quantitative critical appraisal form were determined for all articles
      meeting selection criteria. The primary outcome considered was range-of-motion
      measurement. Overall, the quantity and quality of evidence were moderate to low.
      Sackett's levels 2b, 3, and 4 evidence has shown that joint mobilization, a
      supervised exercise program, and splinting can all increase joint range of
      motion. There were no studies found in the literature that examined techniques of
      physical agent or electrotherapeutic modalities. Future studies are needed to
      delineate selection of appropriate candidates for these techniques and effective
      dosage.

PMID- 15162099
TI  - An introduction to evidence-based practice for hand therapists.
AB  - Evidence-based practice (EBP) is a methodologic approach to clinical practice in
      which evidence is used to reach an informed decision when making a diagnosis,
      selecting a diagnostic test, picking an intervention, or determining a prognosis.
      Finding the best evidence through searching and critical appraisal of the
      methodologic quality of clinical evidence are essential steps. Matching clinical
      recommendations to the level of supporting evidence is expected. Clinicians'
      expertise and patient values are also valued components of decision making in an
      EBP approach. Hand therapists can adopt an EBP approach but must be prepared to
      deal with the challenge of uncertainty when evidence is lacking.

PMID- 15162101
TI  - Extracorporeal shock wave therapy for calcific and noncalcific tendonitis of the
      rotator cuff: a systematic review.
AB  - The authors conducted a systematic review to assess the effectiveness of
      extracorporeal shock wave therapy (ESWT) for the treatment of calcific and
      noncalcific tendonitis of the rotator cuff. Conservative treatment for rotator
      cuff tendonitis includes physiotherapy, nonsteroidal antiinflammatory drugs, and
      corticosteroid injections. If symptoms persist with conservative treatment,
      surgery is often considered. Extracorporeal shock wave therapy has been suggested
      as a treatment alternative for chronic rotator cuff tendonitis, which may
      decrease the need for surgery. Articles for this review were identified by
      electronically searching Medline, EMBASE, Cumulative Index to Nursing & Allied
      Health Literature (CINAHL), and Evidence Based Medicine (EBM) and hand-screening
      references. Two reviewers selected the trials that met the inclusion criteria,
      extracted the data, and assessed the methodological quality of the selected
      trials. Finally, the strength of scientific evidence was appraised. Evidence was
      classified as strong, moderate, limited, or conflicting. Sixteen trials met the
      inclusion criteria. There were only five randomized, controlled trials and all
      involved chronic (>/=3 months) conditions, three for calcific tendonitis and two
      for noncalcific tendonitis. For randomized, controlled trials, two (40%) were of
      high quality, one (33%) for calcific tendonitis and one (50%) for noncalcific
      tendonitis. The 11 nonrandomized trials included nine that involved calcific
      tendonitis and two that involved both calcific and noncalcific tendonitis. Common
      problem areas were sample size, randomization, blinding, treatment provider bias,
      and outcome measures. There is moderate evidence that high-energy ESWT is
      effective in treating chronic calcific rotator cuff tendonitis when the shock
      waves are focused at the calcified deposit. There is moderate evidence that low
      energy ESWT is not effective for treating chronic noncalcific rotator cuff
      tendonitis, although this conclusion is based on only one high-quality study,
      which was underpowered. High-quality randomized, controlled trials are needed
      with larger sample sizes, better randomization and blinding, and better outcome
      measures.

PMID- 15162102
TI  - Effectiveness of rehabilitation for patients with subacromial impingement
      syndrome: a systematic review.
AB  - Prior systematic reviews of rehabilitation for nondescript shoulder pain have not
      yielded clinically applicable results for those patients with subacromial
      impingement syndrome (SAIS). The purpose of this study was to examine the
      evidence for rehabilitation interventions for SAIS. The authors used data source
      as the method. The computerized bibliographic databases of Medline, the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the
      Cochrane Database of Systematic Reviews were searched from 1966 up to and
      including October 2003. Key words used were "shoulder," "shoulder impingement
      syndrome," "bursitis," and "rotator cuff" combined with "rehabilitation,"
      "physical therapy," "electrotherapy," "ultrasound," "acupuncture," and
      "exercise," limited to clinical trials. Randomized clinical trials that
      investigated physical interventions used in the rehabilitation of patients with
      SAIS with clinically relevant outcome measures of pain and quality of life were
      selected. The search resulted in 635 potential studies, 12 meeting inclusion
      criteria. Two independent reviewers graded all 12 trials with a quality checklist
      averaged for a final quality score. The mean quality score for 12 trials was 37.6
      out of a possible 69 points. Various treatments were evaluated: exercise in six
      trials, joint mobilizations in two trials, laser in three trials, ultrasound in
      two trials, and acupuncture in two trials. The limited evidence currently
      available suggests that exercise and joint mobilizations are efficacious for
      patients with SAIS. Laser therapy appears to be of benefit only when used in
      isolation, not in combination with therapeutic exercise. Ultrasound is of no
      benefit, and acupuncture trials present equivocal evidence. The low to mediocre
      methodologic quality, small sample sizes, and general lack of long-term follow-up
      limit these findings for the development of useful clinical practice guidelines.
      Further trials are needed to investigate these rehabilitation interventions, the
      superiority of one intervention over another, and the long-term outcomes of
      rehabilitation. Moreover, it is imperative that clinical guidelines are developed
      to indicate those patients who are likely to respond to rehabilitation.

PMID- 15162103
TI  - Applying evidence on outcome measures to hand therapy practice.
AB  - Standardized outcome measures can enhance clinical decision making in hand
      therapy. Processes in which evidence is used to make decisions on individual
      patients with respect to the patient's level of impairment and disability as well
      as the significance of any changes observed after interventions are consistent
      with an evidence-based approach. Evidence can enhance clinical decision making
      and provide objective criteria for goal setting and evaluation. The authors
      review the necessary concepts and approaches to applying evidence on outcome
      measures using a vignette that describes a patient with rotator cuff pathology
      who has provided a Disability of the Arm, Shoulder, and Hand (DASH) score during
      clinical assessment.

PMID- 15162104
TI  - The effectiveness of hand exercises for persons with rheumatoid arthritis: a
      systematic review.
AB  - A systematic review was conducted to evaluate the efficacy of hand exercises for
      persons with rheumatoid arthritis. The databases Medline, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), EMBASE, PEDro, and Cochrane were
      used to search for articles on exercise and hand and rheumatoid arthritis (and
      their synonyms). Any articles that evaluated the effects of exercise on the hand
      were included in the review and evaluated for quality on a form specifically
      developed for the reviews in this issue. Only nine studies evaluated the effect
      of hand exercise or a program that included hand exercise. Quality scores ranged
      from 21 to 39 out of a possible 48. Few studies used psychometrically sound
      measures or reported on changes to everyday function. Although some significant
      results were obtained, they may have been due to multiple outcome measures, lack
      of blinding, and within-group rather than between-group comparisons. Impairment
      and dexterity were frequent outcomes, but measurement of self-report function was
      lacking. Long-term exercise may increase strength, but results on range of motion
      are inconsistent across studies, subjects, and joints. There is a need for
      randomized controlled trials with goal-specific exercise, measurement of outcomes
      appropriate to the goals, adequate sample size, and comparison with an
      appropriate control condition.

PMID- 15162105
TI  - The efficacy of splinting for lateral epicondylitis: a systematic review.
AB  - To determine the efficacy of using splinting as a treatment for lateral
      epicondylitis (LE), a systematic review of the literature was conducted on
      Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      EMBASE, PEDro, and Cochrane databases using pertinent key words and phrases. Hand
      searches of article references were also used to ensure that as many relevant
      articles as possible were identified. Searches were limited to articles published
      in English. Articles that did not involve splinting (or terminology derivative
      thereof) as treatment intervention for LE were excluded. From 98 potential
      articles, 58 were considered strong inclusion candidates. These articles were
      copied and further triaged according to predefined criteria, resulting in 22
      articles that were numbered randomly and blinded. Three reviewers appraised these
      articles, eliminating 11 of the articles because they did not meet essential
      criteria of randomization, control group, and/or inferential statistical
      analysis. Using MacDermid quality scores, the 11 remaining articles were rated by
      three reviewers. Consensus between the three reviewers was achieved for all
      quality scores for all 11 articles included in the review. Adjusted quality
      scores ranged from 44.5 to 16.5 with a mean of 26.3 points. For accurate
      comparison and consistency of terminology, splints described in the included
      articles were first classified according to the ASHT Splint Classification,
      expanded and refined version, and next according to their inherent material
      properties. Six splints in five classification categories were identified.
      Discussion of the results from the 11 included studies was organized according to
      splint category and further separated into strength, pain, and load applied
      sections. This review identified one Sackett level 1b study and ten Sackett level
      2b studies that offer early positive, but not conclusive, support for the
      effectiveness of splinting lateral epicondylitis. None of the reviewed studies
      received a perfect quality score, and the wide range of quality scores attests to
      the fact that considerable improvement of future studies is essential.

PMID- 15162106
TI  - The quality of clinical practice guidelines in hand therapy.
AB  - Clinical practice guidelines (CPGs) should consist of treatment recommendations
      that assist hand therapists in providing high-quality cost-effective care to
      specific patients based on the highest level of available evidence. This requires
      CPGs to be developed using a rigorous process based on evidence, appraisal of
      both original studies and expert opinion, and a process for multiple reviewers to
      evaluate the draft CPG. This study identified CPGs relevant to hand therapy and
      then evaluated their quality using the AGREE quality assessment tool. The
      majority of guidelines were not evidence-based and were of extremely low quality.
      Two guidelines were produced using a rigorous process that emphasized comparative
      clinical trials. These were able to provide only a single treatment
      recommendation, that ultrasound is effective for calcific tendinitis of the
      shoulder. Hand therapists need to move away from opinion- or clinic-based
      protocols and toward more evidence-based treatment guidelines. However, the value
      of treatment guidelines must be tested, not assumed, regardless of the
      development process.

PMID- 15162108
TI  - The effectiveness of rehabilitation for nonoperative management of shoulder
      instability: a systematic review.
AB  - A systematic review of published evidence on conservative management was
      conducted in Medline, Cumulative Index to Nursing & Allied Health Literature
      (CINAHL), Database of Abstracts of Reviews of Effects (DARE), Allied &
      Alternative Medicine (AMED), PubMed, and Cochrane. For each article, two of the
      four reviewers conducted abstract selection and critical appraisal. Disagreements
      were resolved through consensus and third review, if required. Level of evidence
      and quality on a 24-item quantitative critical appraisal form were determined for
      all articles meeting selection criteria. Outcomes considered included recurrence
      of instability and return to premorbid function. Overall, the quantity and
      quality of evidence were low. Immobilization for three to four weeks followed by
      a structured 12-week rehabilitation program of range of motion and glenohumeral
      and scapular stability exercises for patients with primary dislocations to
      maximize return to premorbid activity level is supported by weak evidence. Level
      II evidence suggests that recurrence is lower in patients managed with surgical
      as compared with conservative management. Further research is required to
      delineate the optimal approach to rehabilitation and its role in secondary
      prevention.

PMID- 15162107
TI  - Effectiveness of hand therapy interventions in primary management of carpal
      tunnel syndrome: a systematic review.
AB  - The purpose of this study was to determine the effectiveness of hand therapy
      interventions for carpal tunnel syndrome (CTS) based on the best available
      evidence. A qualitative systematic review was conducted. A literature search
      using 40 key terms was conducted from the earliest available date to January 2003
      using seven databases. Articles were randomly assigned to two of five reviewers
      and evaluated according to predetermined criteria for inclusion at each of the
      title, abstract, and article levels. Included studies were independently scored
      by two reviewers using a structured effectiveness quality evaluation scale and
      also graded according to Sackett's Levels of Evidence. There were 2027 articles
      identified from the literature search, of which 345 met the inclusion criteria.
      Twenty-four studies were used to formulate 30 recommendations. Current evidence
      demonstrates a significant benefit (grade B recommendations) from splinting,
      ultrasound, nerve gliding exercises, carpal bone mobilization, magnetic therapy,
      and yoga for people with CTS.

PMID- 15162109
TI  - Rehabilitation for patients with lateral epicondylitis: a systematic review.
AB  - The purpose of this systematic review was to determine the effectiveness of
      conservative treatments for lateral epicondylitis and to provide recommendations
      based on this evidence. Five reviewers searched computerized bibliographic
      databases for articles on the conservative treatment of lateral epicondylitis
      from the years 1983 to 2003. A total of 209 studies were located; however, only
      31 of these met the study inclusion criteria. Each of the articles was randomly
      allocated to reviewers and critically appraised using a structured critical
      appraisal tool with 23 items. Treatment recommendations were based on this rating
      and Sackett's Level of Evidence. This review has determined, with at least level
      2b evidence, that a number of treatments, including acupuncture, exercise
      therapy, manipulations and mobilizations, ultrasound, phonophoresis, Rebox, and
      ionization with diclofenac all show positive effects in the reduction of pain or
      improvement in function for patients with lateral epicondylitis. There is also at
      least level 2b evidence showing laser therapy and pulsed electromagnetic field
      therapy to be ineffective in the management of this condition. Practitioners
      should use the treatment techniques that have strongest evidence and ensure that
      studies findings are generalized to patients who are similar to those reported in
      primary research studies in terms of patient demographics and injury
      presentation.

PMID- 15162110
TI  - Effectiveness of workplace rehabilitation interventions in the treatment of work
      related upper extremity disorders: a systematic review.
AB  - The purpose of this systematic review was to evaluate the available evidence on
      workplace rehabilitation interventions for work-related upper extremity disorders
      (WRUEDs). The literature search identified a total of 811 abstracts from Medline,
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), and EMBASE
      databases. The abstracts were independently assessed by four reviewers and 53
      full-text articles were identified. Twenty-one studies were then randomly
      allocated to two pairs of reviewers. Using a 24-item critical appraisal form, the
      reviewers evaluated the articles for quality and level of evidence. During this
      process, an additional 13 articles were discarded, resulting in eight studies.
      The effectiveness of these studies was limited by small sample sizes, lack of
      standardized outcome measures, and inadequate reporting of interventions and
      results. The findings of this review indicate that the evidence for workplace
      interventions for WRUEDs has not been established. This systematic review
      provides a rigorous analysis of workplace interventions for WRUEDs and emphasizes
      the need for further research in this area.

PMID- 15162111
TI  - Evaluation of interventions for rotator cuff pathology: a systematic review.
AB  - A systematic review of published evidence was conducted investigating surgical
      and conservative management of rotator cuff disease. Medical databases searched
      included Medline, the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), the Physiotherapy Evidence Database (PEDro), and the Cochrane
      Collaboration library. Two independent reviewers evaluated each article for
      inclusion. Established criteria were used to assess the methodologic quality of
      articles examining outcomes of treatment interventions for rotator cuff disease.
      Due to the low methodologic quality of the studies that are currently available
      in this area, there is insufficient evidence to strongly support or refute the
      effectiveness of any available treatment intervention for rotator cuff pathology.
      The best available evidence supports open and primary surgery over arthroscopic
      debridement and revision surgery; and in the area of conservative management,
      electrotherapy, steroid use, exercise therapy, and acupuncture. There is a clear
      need for more methodologically sound studies to achieve strong evidence on which
      treatment practices can be based.

PMID- 15162112
TI  - Is there evidence for early mobilization following an extraarticular hand
      fracture?
AB  - The authors conducted a systematic review to determine if there is scientifically
      valid (level I or II) evidence for the effect of early motion (<21 days) of
      joints surrounding an extraarticular hand fracture on fracture healing or
      functional outcomes. Two reviewers independently evaluated for study inclusion,
      trial quality and internal validity. Six poor-quality, quasirandomized studies
      (level III evidence) involving 459 patients were included. Findings suggest that
      in simple, closed metacarpal fractures, early motion (EM) has the potential to:
      (1) result in earlier recovery of mobility and strength, (2) facilitate an
      earlier return to work, and (3) not affect fracture alignment. Findings also
      indicate that skin pressure problems are not associated with custom-molded
      metacarpal fracture braces. The scientific validity of EM interventions after an
      extraarticular hand fracture has not been established in well-conducted,
      randomized, controlled trials (level I or II evidence). Current evidence does not
      support or refute the use of EM after an extraarticular hand fracture. However,
      further investigations are warranted, as findings to date show a consistent
      potential for benefit with no significant risk of harm when early regional joint
      motions are incorporated into the management of closed, extraarticular, finger
      metacarpal fractures.

PMID- 15162113
TI  - Clinical diagnosis of carpal tunnel syndrome: a systematic review.
AB  - The purposes of this systematic review were to examine the properties of clinical
      tests used in the diagnosis of carpal tunnel syndrome (CTS) and to provide
      estimates of their sensitivity and specificity. A literature search was conducted
      using two databases-PubMed and the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL)-from 1986 to June 2003, and hand-searching reference lists of
      retrieved articles. Two reviewers evaluated the papers for quality using an
      evaluation tool developed by one of the authors. Estimates of sensitivity and
      specificity were determined by averaging values across studies weighted by sample
      size. Although 60 studies were reviewed in detail, many were of poor quality
      (mean quality score was 6.6 of 12, with only 15 of 60 obtaining a score of 8 or
      greater). The most frequently studied test was Phalen's, with an overall estimate
      of 68% sensitivity and 73% specificity. Next was Tinel's, with estimates of 50%
      and 77%, and then carpal compression, with estimates of 64% and 83% for
      sensitivity and specificity, respectively. Two-point discrimination and testing
      of atrophy or strength of the abductor pollicis brevis proved to be specific but
      not very sensitive. The estimates determined in this review should help
      therapists choose clinical tests with the appropriate balance of sensitivity and
      specificity required for diagnosing carpal tunnel syndrome in their specific
      clinical environments.

PMID- 15162114
TI  - Genes without frontiers?
AB  - For bacteria, the primary genetic barrier against the genetic exchange of DNA
      that is not self-transmissible is dissimilarity in the bacterial DNA sequences
      concerned. Genetic exchange by homologous recombination is frequent among close
      bacterial relatives and recent experiments have shown that it can enable the
      uptake of closely linked nonhomologous foreign DNA. Artificial vectors are
      mosaics of mobile DNA elements from free-living bacterial isolates and so bear a
      residual similarity to their ubiquitous natural progenitors. This homology is
      tightly linked to the multitude of different DNA sequences that are inserted into
      synthetic vectors. Can homology between vector and bacterial DNA enable the
      uptake of these foreign DNA inserts? In this review we investigate pUC18 as an
      example of an artificial vector and consider whether its homology to broad host
      range antibiotic resistance transposons and plasmid origins of replication could
      enable the uptake of insert DNA in the light of studies of homology-facilitated
      foreign DNA uptake. We also discuss the disposal of recombinant DNA, its
      persistence in the environment and whether homologies to pUC18 may exist in
      naturally competent bacteria. Most DNA that is inserted into the cloning site of
      artificial vectors would be of little use to a bacterium, but perhaps not all.

PMID- 15162115
TI  - Mitochondrial simple sequence repeats and 12S-rRNA gene reveal two distinct
      lineages of Crocidura russula (Mammalia, Soricidae).
AB  - A short segment (135 bp) of the control region and a partial sequence (394 bp) of
      the 12S-rRNA gene in the mitochondrial DNA of Crocidura russula were analyzed in
      order to test a previous hypothesis regarding the presence of a gene flow
      disruption in northern Africa. This breakpoint would have separated northeast
      African C. russula populations from the European (plus the northwest-African)
      populations. The analysis was carried out on specimens from Tunisia (C. r. cf
      agilis), Sardinia (C. r. ichnusae), and Pantelleria (C. r. cossyrensis), and on
      C. r. russula from Spain and Belgium. Two C. russula lineages were identified;
      they both shared R2 tandem repeated motifs of the same length (12 bp), but not
      the same primary structure. These simple sequence repeats were present in 12-23
      copies in the right domain of the control region. Within the northeast-African
      populations, a polymorphism of repeat variants, not yet found in Europe, was
      recorded. A neighbor-join tree, which was built by sequences of the conserved 12S
      rRNA gene, separated the two sister groups; it permitted us to date a divergence
      time of 0.5 Myr. Our data discriminated two different mitochondrial lineages in
      accordance with the previous morphological and karyological data. Ecoclimatic
      barriers formed during the Middle Pleistocene broke the range of ancestral
      species in the Eastern Algeria (Kabile Mountains), leading to two genetically
      separate and modern lineages. The northeast-African lineage can today be located
      in Tunisia, Pantelleria, and Sardinia. The northwest-African lineage (Morocco and
      West Algeria), reaching Spain by anthropogenic introduction, spread over north
      Europe in modern times. The Palaearctic C. russula species is monophyletic, but a
      taxonomical revision (ie, to provide a full species rank for the northeast taxa
      and to put in synonymy some insular taxa) is required.

PMID- 15162117
TI  - Genetic relationship between olfactory response and fitness in Cotesia glomerata
      (L.).
AB  - The flight response of the parasitic wasp Cotesia glomerata (L.) to
      semiochemicals from a plant-host complex is subject to genetic variation. The
      significance of additive genetic variance for the odour-guided behaviour has been
      demonstrated by bidirectional selection. In order to understand the potential and
      constraints for phenotypic evolution in olfactory response under the pressure of
      natural selection, this study was to investigate genetic covariation between the
      odour-guided behaviour and life-history traits and its genetic correlation with
      the efficiency of parasitism. A paternal half-sib analysis revealed that there
      was no significant genetic correlation between this behavioural character and any
      of three life-history traits examined (the development time of immature stages,
      the body size of female wasps, the number of female wasps per brood). Comparisons
      between the selected high and low olfactory-response strains showed the lack of
      correlated responses in these life-history traits to bidirectional selection on
      the odour-guided behaviour. On the other hand, genotypic differences in the
      ability of olfactory response significantly affected the efficiency of
      parasitism. In comparison with the low olfactory-response strain, female wasps
      from the high olfactory-response strain were able to parasitize more host larvae
      in a wider area of habitats. This study provides the first evidence of links
      between olfactory response and population success in parasitoids from a genetic
      perspective.

PMID- 15162116
TI  - MHC class I typing in a songbird with numerous loci and high polymorphism using
      motif-specific PCR and DGGE.
AB  - The major histocompatibility complex (MHC) has a central role in the specific
      immune defence of vertebrates. Exon 3 of MHC class I genes encodes the domain
      that binds and presents peptides from pathogens that trigger immune reactions.
      Here we develop a fast population screening method for detecting genetic
      variation in the MHC class I genes of birds. We found evidence of at least 15
      exon 3 sequences in the investigated great reed warbler individual. The
      organisation of the great reed warbler MHC class I genes suggested that a locus
      specific screening protocol is impractical due to the high similarity between
      alleles across loci, including the introns flanking exon 3. Therefore, we used
      motif-specific PCR to amplify two subsets of alleles (exon 3 sequences) that were
      separated with by DGGE. The motif-specific primers amplify a substantial
      proportion of the transcribed class I alleles (2-12 alleles per individual) from
      as many as six class I loci. Although not exhaustive, this gives a reliable
      estimate of the class I variation. The method is highly repeatable and more
      sensitive in detecting genetic variation than the RFLP method. The motif-specific
      primers also allow us to avoid screening pseudogenes. In our study population of
      great reed warblers, we found a high level of genetic variation in MHC class I,
      and no less than 234 DGGE genotypes were detected among 248 screened individuals.

PMID- 15162123
TI  - Tools for molecular risk-stratification for clinical purposes: CLL as a
      prototype.

PMID- 15162118
TI  - Correlations between fitness and heterozygosity at allozyme and microsatellite
      loci in the Atlantic salmon, Salmo salar L.
AB  - The relationship between heterozygosity at genetic markers (six allozyme and
      eight microsatellite loci), and fluctuating asymmetry (FA), length and weight was
      investigated in two samples of Atlantic salmon (Salmo salar L.) with different
      timings of first active feeding (early (EA) and late (LA) salmon). This trait had
      previously been related to fitness. EA fish show smaller values of FA, are
      longer, heavier and are more heterozygous at allozyme loci than are conspecific
      LA fish. Also within both samples, heterozygosity at allozyme loci was inversely
      related to FA and was positively related to weight and length. However, no
      significant differences in microsatellite diversity (heterozygosity and mean d2
      measurements) were observed between samples (EA vs LA). Furthermore, no
      association was observed between the variability at microsatellite loci and FA,
      weight or length within each sample. These results suggest that allozyme loci, in
      themselves, influence fitness components, rather than associations arising from
      associative overdominance.

PMID- 15162124
TI  - Remarkable variability in renal disease in a large Slovenian family with Fabry
      disease.
AB  - Following the diagnosis of Fabry disease in a 45-year-old male, in 31 family
      members alpha-galactosidase A (alpha-Gal) activity in leucocytes was measured and
      mutation analysis of the alpha-Gal gene was performed. In the proband, the unique
      mutation A10523G/N272S in exon 6 was found, which was subsequently detected in
      seven males (of which one twin) and 10 female subjects. All males showed
      decreased to absent alpha-Gal A activity in leucocytes, but three out of 10
      female subjects had alpha-Gal A activities within normal range. Although all male
      patients had symptoms of classical Fabry disease, such as acroparesthesias,
      hypohydrosis and heat-intolerance, there was considerable variability in organ
      involvement, especially in deterioration of renal function. Detailed studies of
      large families with Fabry disease may give insight into factors that influence
      the phenotype of this disorder.

PMID- 15162125
TI  - Fluorescence in situ hybridization characterization of apparently balanced
      translocation reveals cryptic complex chromosomal rearrangements with unexpected
      level of complexity.
AB  - The great majority of apparently balanced translocations are associated with
      multiple miscarriages and normal phenotype. Several mechanisms have been proposed
      to explain how a small percentage of apparently balanced translocations are
      associated with abnormal phenotypes. One of the proposed mechanisms that have not
      been well investigated is that apparently balanced translocations may host
      'cryptic' complex chromosomal rearrangements (CCRs). To test this hypothesis,
      this study investigated 20 non-preselected cases with apparently balanced
      translocations in order to determine the presence of cryptic CCRs. Multiprobe
      subtelomeric and whole chromosome paint FISH analyses revealed and further
      characterized three cryptic CCRs. Two out of three CCRs showed an unexpected
      level of complexity. The results of this study provided evidence that the link
      between an apparently balanced rearrangement and the appearance of abnormal
      phenotype may be partly explained by the presence of cryptic CCRs. The results
      also suggested that what is reported as apparently balanced translocation by
      classical cytogenetics may host cryptic CCRs, which could be more common than
      initially thought. Furthermore, the use of both of the above-mentioned FISH
      methodologies was absolutely necessary to detect the CCRs.

PMID- 15162126
TI  - Survival motor neuron SMN1 and SMN2 gene promoters: identical sequences and
      differential expression in neurons and non-neuronal cells.
AB  - Spinal muscular atrophy (SMA) is a recessive disorder involving the loss of motor
      neurons from the spinal cord. Homozygous absence of the survival of motor neuron
      1 gene (SMN1) is the main cause of SMA, but disease severity depends primarily on
      the number of SMN2 gene copies. SMN protein levels are high in normal spinal cord
      and much lower in the spinal cord of SMA patients, suggesting neuron-specific
      regulation for this ubiquitously expressed gene. We isolated genomic DNA from
      individuals with SMN1 or SMN2 deletions and sequenced 4.6 kb of the 5' upstream
      regions of the these. We found that these upstream regions, one of which is
      telomeric and the other centromeric, were identical. We investigated the early
      regulation of SMN expression by transiently transfecting mouse embryonic spinal
      cord and fibroblast primary cultures with three transgenes containing 1.8, 3.2
      and 4.6, respectively, of the SMN promoter driving beta-galactosidase gene
      expression. The 4.6 kb construct gave reporter gene expression levels five times
      higher in neurons than in fibroblasts, due to the combined effects of a general
      enhancer and a non-neuronal cell silencer. The differential expression observed
      in neurons and fibroblasts suggests that the SMN genes play a neuron-specific
      role during development. An understanding of the mechanisms regulating SMN
      promoter activity may provide new avenues for the treatment of SMA.

PMID- 15162127
TI  - Difference in allelic expression of the CLCN1 gene and the possible influence on
      the myotonia congenita phenotype.
AB  - Mutations in the CLCN1 gene, encoding a muscle-specific chloride channel, can
      cause either recessive or dominant myotonia congenita (MC). The recessive form,
      Becker's myotonia, is believed to be caused by two loss-of-function mutations,
      whereas the dominant form, Thomsen's myotonia, is assumed to be a consequence of
      a dominant-negative effect. However, a subset of CLCN1 mutations can cause both
      recessive and dominant MC. We have identified two recessive and two dominant MC
      families segregating the common R894X mutation. Real-time quantitative RT-PCR did
      not reveal any obvious association between the total CLCN1 mRNA level in muscle
      and the mode of inheritance, but the dominant family with the most severe
      phenotype expressed twice the expected amount of the R894X mRNA allele. Variation
      in allelic expression has not previously been described for CLCN1, and our
      finding suggests that allelic variation may be an important modifier of disease
      progression in myotonia congenita.

PMID- 15162128
TI  - A transmission disequilibrium test for general pedigrees that is robust to the
      presence of random genotyping errors and any number of untyped parents.
AB  - Two issues regarding the robustness of the original transmission disequilibrium
      test (TDT) developed by Spielman et al are: (i) missing parental genotype data
      and (ii) the presence of undetected genotype errors. While extensions of the TDT
      that are robust to items (i) and (ii) have been developed, there is to date no
      single TDT statistic that is robust to both for general pedigrees. We present
      here a likelihood method, the TDT(ae), which is robust to these issues in general
      pedigrees. The TDT(ae) assumes a more general disease model than the traditional
      TDT, which assumes a multiplicative inheritance model for genotypic relative
      risk. Our model is based on Weinberg's work. To assess robustness, we perform
      simulations. Also, we apply our method to two data sets from actual diseases:
      psoriasis and sitosterolemia. Maximization under alternative and null hypotheses
      is performed using Powell's method. Results of our simulations indicate that our
      method maintains correct type I error rates at the 1, 5, and 10% levels of
      significance. Furthermore, a Kolmorogov-Smirnoff Goodness of Fit test suggests
      that the data are drawn from a central chi2 with 2 df, the correct asymptotic
      null distribution. The psoriasis results suggest two loci as being significantly
      linked to the disease, even in the presence of genotyping errors and missing
      data, and the sitosterolemia results show a P-value of 1.5 x 10(-9) for the
      marker locus nearest to the sitosterolemia disease genes. We have developed
      software to perform TDT(ae) calculations, which may be accessed from our ftp
      site.

PMID- 15162129
TI  - Haplotype analysis of BRCA1 gene reveals a new gene rearrangement:
      characterization of a 19.9 KBP deletion.
AB  - Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast
      and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk
      families. Mutation-screening methods generally focus on genomic DNA and are
      usually PCR based; they enable the detection of sequence alterations such as
      point mutations and small deletions and insertions. However, they do not allow
      the detection of partial or entire exon(s) loss, because the presence of the
      homologous allele results in a positive PCR signal, giving rise to a false
      negative result. Identification of unusual haplotypes in patient samples by an
      expectation maximization algorithm has recently been suggested as a method for
      identifying hemizygous regions caused by large intragenic deletions. Using a
      similar approach, we identified a novel BRCA1 genomic rearrangement in a
      breast/ovarian cancer family negative at the first mutation screening; we
      detected a deletion encompassing exons 14-19, probably due to replication
      slippage between Alu sequences.

PMID- 15162130
TI  - Healthy Eating Index and obesity.
AB  - BACKGROUND: There is a continuing need to examine the relationship between diet
      quality and health in the population. The Healthy Eating Index (HEI) has been
      developed as a composite measure of diet quality by the US Department of
      Agriculture. OBJECTIVES: The first objective was to use the HEI to assess the
      diet quality of a representative sample of the US population and population
      groups. The second objective was to examine the association between HEI and
      obesity. DESIGN: Cross-sectional analysis of data from 10 930 adults who
      participated in the Third National Health and Nutrition Examination Survey.
      Sociodemographic, physical activity, dietary, and health data were used in the
      analysis. Diet quality was assessed with the HEI score, ranging from 0 to 100,
      based on 10 dietary criteria. A low HEI score indicates poor diet. RESULTS: A
      majority of survey participants had a low HEI score. The percentage of
      individuals classified as having a poor diet varied by age, gender,
      race/ethnicity, income, and education. A low HEI score was associated with
      overweight and obesity. There was a graded increase in the odds ratio of obesity
      across the HEI category after adjusting for age, gender, race/ethnicity, physical
      activity, smoking, alcohol use, income, and education. CONCLUSIONS: An index of
      diet quality, such as HEI, may provide a comprehensive assessment of diet in the
      population. Since the HEI is based on the US Dietary Guidelines, the use of these
      guidelines as a way to improve health should be emphasized. However, the overall
      effectiveness of these guidelines in disease prevention needs to be studied
      further.

PMID- 15162131
TI  - Cereal grains, legumes and diabetes.
AB  - This review examines the evidence for the role of whole grain foods and legumes
      in the aetiology and management of diabetes. MedLine and SilverPlatter
      ('Nutrition' and 'Food Science FSTA') databases were searched to identify
      epidemiological and experimental studies relating to the effects of whole grain
      foods and legumes on indicators of carbohydrate metabolism. Epidemiological
      studies strongly support the suggestion that high intakes of whole grain foods
      protect against the development of type II diabetes mellitus (T2DM). People who
      consume approximately 3 servings per day of whole grain foods are less likely to
      develop T2DM than low consumers (<3 servings per week) with a risk reduction in
      the order of 20-30%. The role of legumes in the prevention of diabetes is less
      clear, possibly because of the relatively low intake of leguminous foods in the
      populations studied. However, legumes share several qualities with whole grains
      of potential benefit to glycaemic control including slow release carbohydrate and
      a high fibre content. A substantial increase in dietary intake of legumes as
      replacement food for more rapidly digested carbohydrate might therefore be
      expected to improve glycaemic control and thus reduce incident diabetes. This is
      consistent with the results of dietary intervention studies that have found
      improvements in glycaemic control after increasing the dietary intake of whole
      grain foods, legumes, vegetables and fruit. The benefit has been attributed to an
      increase in soluble fibre intake. However, prospective studies have found that
      soluble fibre intake is not associated with a lower incidence of T2DM. On the
      contrary, it is cereal fibre that is largely insoluble that is associated with a
      reduced risk of developing T2DM. Despite this, the addition of wheat bran to the
      diets of diabetic people has not improved indicators of glycaemic control. These
      apparently contradictory findings might be explained by metabolic studies that
      have indicated improvement in glucose handling is associated with the intact
      structure of food. For both grains and legumes, fine grinding disrupts cell
      structures and renders starch more readily accessible for digestion. The extent
      to which the intact structure of grains and legumes or the composition of foods
      in terms of dietary fibre and other constituents contribute to the beneficial
      effect remains to be quantified. Other mechanisms to help explain improvements in
      glycaemic control when consuming whole grains and legumes relate to cooking, type
      of starch, satiety and nutrient retention. Thus, there is strong evidence to
      suggest that eating a variety of whole grain foods and legumes is beneficial in
      the prevention and management of diabetes. This is compatible with advice from
      around the world that recommends consumption of a wide range of carbohydrate
      foods from cereals, vegetables, legumes and fruits both for the general
      population and for people with diabetes.

PMID- 15162132
TI  - Plasma AA and DHA levels are not compromised in newly diagnosed gestational
      diabetic women.
AB  - OBJECTIVE: The polyunsaturated fatty acids, arachidonic (AA) and docosahexaenoic
      (DHA), are vital structural and functional components of the neural, vascular and
      visual systems. There is increased demand for these fatty acids during pregnancy.
      Diabetes impairs the synthesis of both AA and DHA. We have investigated the
      possibility that pregnancy-induced diabetes compromises the levels of plasma AA
      and DHA in newly diagnosed expectant mothers. DESIGN: Cross-sectional study.
      SETTING: London, UK. SUBJECTS AND METHODS: Venous blood was obtained from 44
      women with gestational diabetes mellitus (GDM) and from the same number of
      nondiabetics, during the third trimester. Fatty acid composition of plasma
      choline phosphoglycerides (CPG), triglycerides (TG) and cholesterol esters (CE)
      was analysed. RESULTS: The GDM women had higher levels of AA (20:4n-6; P<0.0001)
      and AA/linoleic acid ratio (20:4n-6/18:2n-6; P<0.01) in the CPG, and linoleic
      acid (LA; P<0.0001), total n-6 (P<0.01), DHA (P<0.05) and n-3 metabolites
      (P<0.05) in TG compared to their nondiabetic counterparts. Similarly, AA
      (P<0.0001), osbond acid (22:5n-6; P<0.05), total n-6 metabolites (P<0.0001),
      AA/LA (P<0.0001) and n-6 metabolites/LA (P<0.01) were higher in the CE of the GDM
      women. There was no difference in the levels of DHA in CPG and CE between the two
      groups (P>0.05). CONCLUSIONS: The results of this study do not provide evidence
      that the activity of delta-6 or delta-5 desaturases, which are vital for the
      synthesis of AA and DHA, is compromised by pregnancy-induced diabetes. However,
      since the samples were taken at diagnosis, it is conceivable that the duration of
      the diabetes was too short to have a discernable adverse effect on the levels of
      AA and DHA in plasma lipids.

PMID- 15162133
TI  - Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient
      Indonesian infants.
AB  - OBJECTIVE: To determine effects of vitamin A, zinc and iron deficiency in
      Indonesian infants on the ability to produce immunoregulatory cytokines. DESIGN,
      SETTING AND SUBJECTS: Immunological assessment was done in 59 infants
      participating in a cross-sectional nutritional survey in rural West Java,
      Indonesia. Production of T-helper cell type-1 (Th1, cell-mediated) cytokines
      interferon-gamma (IFN-gamma), interleukin-12 (IL-12), interleukin-18 (IL-18) and
      T-helper cell type-2 (Th2, humoral) cytokine interleukin-6 (IL-6) were measured
      after stimulation with lipopolysaccharide and phytohemagglutinin in an ex vivo
      whole blood culture system. Circulating neopterin concentrations were determined
      as an indicator of in vivo macrophage activity. RESULTS: Of the infants, 48% were
      vitamin A deficient, 44% were anemic (with 17% having iron deficiency anemia),
      and 17% were zinc deficient. Vitamin-A deficient infants had significantly
      reduced ex vivo production of IFN-gamma, but also significantly higher
      circulating neopterin concentrations. Production of IFN-gamma and IL-12 were
      strongly correlated, IFN-gamma and IL-18 production were not. Zinc deficiency was
      accompanied by significantly reduced white blood cell counts and reduced ex vivo
      production of IL-6. Iron status was not related to cytokine production.
      CONCLUSIONS: This study shows that in vitamin A deficiency there is Th1 dominance
      in a steady state, combined however with impairment of the Th1 response after
      stimulation, whereas in zinc deficiency, there is a decreased Th2 response.
      Overall, vitamin A deficiency and zinc deficiency have marked albeit different
      effects on the immunocompetence of infants, affecting both cell-mediated and
      humoral components of the immune system.

PMID- 15162134
TI  - Free and bound leptin in prepubertal children with Down's syndrome and different
      degrees of adiposity.
AB  - OBJECTIVE: To evaluate plasma total, free (FL) and protein-bound (BL) leptin in
      children with Down's syndrome (DS) and different degrees of adiposity and its
      relationship with thyroid stimulating hormone (TSH), free thyroxine (FT(4)), and
      free triiodothyronine (FT(3)). SUBJECTS: A total of 24 prepubertal clinically
      euthyroid DS children. METHODS: Plasma leptin, TSH, FT(4), and FT(3)
      concentrations were determined by immunometric/radioimmunologic assays. FL and BL
      were evaluated by fast protein liquid chromatography. RESULTS: In DS children,
      leptin circulates in two fractions, corresponding to BL and FL. The amount of BL
      and FL is negatively and positively correlated to body mass index (BMI),
      respectively. Plasma leptin concentrations correlate with BMI, but not with TSH,
      FT(4), and FT(3). CONCLUSIONS: In prepubertal DS children, leptin circulates as
      both BL and FL, correlates with adiposity and its concentration appears
      independent of thyroid function.

PMID- 15162135
TI  - Comparison of anthropometry to DXA: a new prediction equation for men.
AB  - OBJECTIVE: This study compared three professionally recommended anthropometric
      body composition prediction equations for men to dual energy X-ray absorptiometry
      (DXA), and then developed an updated equation, DXA Criterion (DC) from DXA.
      DESIGN: Cross-sectional. SETTING: Exercise Physiology Lab. University of Missouri
      Columbia, USA. SUBJECTS: A total of 160 men aged 18-62 y old. INTERVENTIONS:
      Percent body fat (%BF) by anthropometry was compared to DXA on the same day.
      RESULTS: Although %BF was significantly correlated (r=0.923-0.942) (P<0.01) with
      DXA for all three equations, each equation underestimated %BF (range=3.1-3.3%)
      (P<0.01) compared to DXA. The following DC equation for men was created:
      %BF=0.465+0.180(Sigma7SF)-0.0002406(Sigma7SF)(2)+0.06619(age); (Sigma7SF=sum of
      chest, midaxillary, triceps, subscapular, abdomen, suprailiac, thigh; age=years).
      The predicted residual sum of squares (PRESS) R(2) was high (0.90) and the PRESS
      standard error of estimates was excellent (2.2% at the mean) for the DC equation
      when applied to our sample of 160 men. CONCLUSIONS: The currently recommended
      anthropometric equations for men underestimate %BF compared to DXA. The DC
      equation yields a more accurate estimation of %BF in men aged 18-62 y old. The
      results from this study support the need for the current %BF standards and norms
      for men to be adjusted upward.

PMID- 15162136
TI  - Development of a short dietary intake questionnaire for the quantitative
      estimation of adherence to a cardioprotective Mediterranean diet.
AB  - Our objective was to develop a short questionnaire that can be easily used to
      estimate quantitatively the level of adherence to cardioprotective Mediterranean
      diets. The short questionnaire assessed the consumption of cardioprotective
      elements included in the Mediterranean diet (olive oil, wine, fruits, vegetables,
      fish, legumes and whole-grain intake). A low consumption of meat or meat-products
      was also included in the composite score. The relative risk of myocardial
      infarction for each category of the composite score obtained (range 0-9) was
      computed using data from a case-control study that included 171 cases of first
      myocardial infarction and 171 matched controls. We found an adjusted odds
      ratio=0.18 (95% confidence interval (CI): 0.03-0.97; P=0.04) for those scoring 7
      9 points when comparing them with those scoring 1-2 points. An increment of one
      point in the score was associated with an 18% reduction in the relative risk of
      myocardial infarction (P=0.05).

PMID- 15162138
TI  - Comment on validity of glycaemic glucose equivalent.

PMID- 15162137
TI  - Dietary acid-base balance and intake of bone-related nutrients in Cambridge
      teenagers.
AB  - OBJECTIVES: To evaluate the diet of 16-18-y-old boys and girls with particular
      reference to intakes of nutrients believed to affect bone health and dietary acid
      base balance. DESIGN: A 7-day food diary was completed between the months of
      October and December. SETTING: Cambridge, UK. SUBJECTS: A total of 111 boys and
      101 girls aged 16-18 y who were recruited into the Cambridge Bone Studies. MAIN
      OUTCOME MEASURES: Mean daily intakes of foods and selected nutrients (protein,
      calcium, phosphorus, magnesium, potassium, vitamins C and K) were calculated. Two
      estimates of acid-base balance were calculated from the diet using the formulae
      of Remer (net acid excretion, estimated indirectly; NAE(ind)) and Frassetto
      (protein/potassium ratio). RESULTS: Mean calcium and phosphorus intakes were
      above the UK Reference Nutrient intake (RNI). In all, 39% of the boys and 36% of
      the girls had vitamin K intakes lower than 1 microg/kg body weight/day. Calcium
      intake was positively correlated with all other nutrients except vitamins C and
      K. Boys had a significantly higher estimated net acid excretion (NAE(ind)) than
      girls (P<0.001). Although a strong correlation (r=0.76, P<0.001) was found
      between the two methods, at higher acid levels a divergence was observed. A
      significant positive correlation was found between NAE(ind) and the weight
      consumed per day of milk, cheese, meat and cereal foods and a negative
      correlation was found with the weight of potatoes and fruit. Diet composition is
      such that a lower NAE(ind) is accompanied by a lower calcium intake. CONCLUSIONS:
      The interpretation of the effects of calcium and other nutrients on bone cannot
      be considered in isolation from the other components of the diet. These results
      challenge some of the accepted perceptions about what constitutes an optimal diet
      for the promotion of bone health in adolescents.

PMID- 15162139
TI  - The first randomized clinical trial of 2 y to prevent reinfarction with fish oil.

PMID- 15162140
TI  - Energetic determinants of glucose tolerance status in Jamaican adults.
AB  - As type 2 diabetes mellitus (DM2), obesity and sedentary lifestyles are
      increasing in developing countries, this observational study investigated the
      role of physical activity on DM2 in Jamaica. Anthropometry, body composition (by
      bioelectrical impedance analysis) and glucose tolerance status was assessed in
      722 adults in 1993 and 1997. Energy expenditure was estimated in a subset using
      measured resting energy expenditure in combination with self-reported activity
      recalls. The rates of impaired glucose tolerance (IGT) were 23.7 and 27.3%, and
      DM2 were 16.3 and 23.7% among men and women, respectively. After adjusting for
      body composition, a one-unit increase in physical activity significantly reduced
      the odds of having diabetes (OR = 0.05; 95% CI: 0.004, 0.66), but not IGT. Hence,
      decreased physical activity is a significant independent contributor to the high
      rates of glucose intolerance in Jamaica. Efforts must be directed at minimizing
      obesity and increasing physical activity in developing countries.

PMID- 15162141
TI  - Correlations between family history and cancer characteristics in 2256 breast
      cancer patients.
AB  - A comparison of 692 early invasive breast cancer with, and 1564 without, a family
      history of breast cancer showed that the former were younger at diagnosis
      (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor
      positive (P=0.006) and diagnosed preclinically (P<0.001).

PMID- 15162142
TI  - Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood
      survivors of a solid tumour at the Institut Gustave Roussy.
AB  - The purpose of this paper was to determine the cardiac status in children 15
      years or more after adriamycin therapy for a solid tumour. Of the 447 pts, 229
      pts were fully studied and 218 were not. The following cardiac evaluations were
      proposed to all the 447 consecutive patients (pts): (1) cardiac Doppler US by one
      of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities
      including 24-hour holter ECG; (3) (131)l-mlBG myocardial scintigraphy; (4) serum
      brain natriuretic peptide levels at rest; (5) an exercise test with VO(2) max
      measurement. The radiation doses delivered to 6 points in the heart were
      estimated for all patients who had received radiotherapy. Congestive heart
      failure was diagnosed in 24 of 229 (10%) evaluated pts, with a median interval of
      15 years (0.3-24 years) from the first symptom after adriamycin treatment. Among
      the 205 remaining pts, 13 asymptomatic pts (6%) had severe (n=4) (FS<20%) or
      marked (n=9) (20< or =FS<25%) systolic dysfunction. In the 192 others, the median
      meridional end-systolic wall stress was 91 (53-135) and it exceeded 100 g cm(-2)
      in 52 pts. Using a Cox model, only the cumulative dose of adriamycin and the
      average radiation dose to the heart, were identified as risk factors for a
      pathological cardiac status. In conclusion, the risk of cardiac failure or severe
      abnormalities increases with adriamycin treatment, radiotherapy and time since
      treatment, even after a follow-up of 15 years or more. In our series, after an
      average follow-up of 18 years, 39% of the children had a severe cardiac
      dysfunction or major ventricular overload conditions. The risk increases with the
      dose of adriamycin and radiation received to the heart, without evidence for
      threshold.

PMID- 15162143
TI  - The impact of the perception of treatment choice on satisfaction with treatment,
      experienced chemotherapy burden and current quality of life.
AB  - Previous research has shown that involving patients in the decision-making
      process may improve their quality of life (QoL). Our purposes were to assess: (1)
      whether early-stage breast cancer patients perceived that they had treatment
      choice with regard to adjuvant chemotherapy, (2) what reasons patients provide
      for their perception of having had no choice of treatment and (3) whether the
      perception of treatment choice is related to satisfaction with the assigned
      treatment, experienced chemotherapy burden and current QoL. A total of 448
      patients, treated between 1998 and 2003, filled in the questionnaire (response
      rate: 62%). Patients who indicated that they had not perceived a choice regarding
      chemotherapy could tick off one or more reasons out of 10 reasons, or provide
      their own reason(s). Quality of life was measured on a Visual Analogue Scale, by
      means of the EuroQol, and by means of the Hospital Anxiety and Depression Scale.
      Of the 405 patients who had answered the question on treatment choice, 316
      patients (78%) had perceived no choice. The most frequently indicated reason for
      lack of choice was: "I follow the doctor's advice." We found no differences in
      the levels of satisfaction with assigned treatment and in how much of a burden
      they found chemotherapy between patients who perceived a choice of treatment and
      those who did not. In general, the perception of choice seemed to have no impact
      on QoL. However, we found an interaction effect, which indicated that the impact
      of perception of treatment choice on QoL was dependent upon whether the patient
      had been treated with chemotherapy or not. Within the group of patients who had
      not been treated with chemotherapy, the perception of having had a choice was
      related to lower current QoL. In cases when the decision to be treated or not has
      potential consequences for the chance of survival, patients' QoL may not be
      improved by the perception of having had a choice of treatment.

PMID- 15162144
TI  - Resveratrol inhibits benzo[a]pyrene-DNA adduct formation in human bronchial
      epithelial cells.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin present in various
      plants and foods, has in several in vitro and in vivo studies demonstrated cancer
      chemopreventive and chemotherapeutic potential. We investigated the in vitro
      effect of resveratrol on benzo[a]pyrene (B[a]P) -induced DNA adducts in human
      bronchial epithelial cells. This was compared to the effect of resveratrol on the
      expression of the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1 and the formation
      of B[a]P metabolites. Exposure of BEAS-2B and BEP2D cells to B[a]P and increasing
      concentrations of resveratrol resulted in a dose- and time-dependent inhibition
      of DNA adduct formation quantified by (32)P-postlabelling. Supporting this
      result, resveratrol was shown to inhibit CYP1A1 and CYP1B1 gene expression, as
      measured by real-time reverse transcriptase-polymerase chain reaction. Also, a
      significant correlation was found between the number of DNA adducts and the mRNA
      levels of these genes. Using HPLC analysis, a concomitant decrease in the
      formation of B[a]P-derived metabolic products was detected. In conclusion, these
      data lend support to a chemopreventive role of resveratrol in polycyclic aromatic
      hydrocarbon-induced carcinogenesis.

PMID- 15162146
TI  - Patterns of failure in gastric carcinoma after D2 gastrectomy and
      chemoradiotherapy: a radiation oncologist's view.
AB  - The risk of locoregional recurrence in resected gastric adenocarcinoma is high,
      but the benefit of adjuvant treatment remains controversial. In particular, after
      extended lymph node dissection, the role of radiotherapy is questionable. Since
      1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2
      gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant
      chemotherapy consisted of five cycles of fluorouracil and leucovorin, and
      concurrent radiotherapy was given with 4500 cGy from the second cycle of
      chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any
      type of failure, and the local and regional failures were seen in 7% (20 out of
      291) and 12% (35 out of 291), respectively. When the recurrent site was analysed
      with respect to the radiation field, in-field recurrence was 16% and represented
      35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a
      potential effect on reducing locoregional recurrence. Moreover, low locoregional
      recurrence rates could give a clue as to which subset of patients could be helped
      by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on
      the role of adjuvant radiotherapy, a randomised study is needed.

PMID- 15162147
TI  - The meanings of cancer and perceptions of cancer services among South Asians in
      Luton, UK.
AB  - Recent research has suggested that there is limited awareness of and information
      about cancer and cancer services among South Asian communities. This study
      explores the meanings of cancer and perceptions of cancer services among South
      Asians living in Luton. Six single-sex focus groups were conducted among the
      three main South Asian groups in Luton: (1) Punjabi-speaking Muslims originating
      from Pakistan (Pakistani Punjabi); (2) Sylheti-speaking Muslims originating from
      Bangladesh (Bangladeshi Sylheti); and (3) Punjabi-speaking Sikhs originating from
      the Indian Punjab (Indian Punjabi). Overall, it was found that the information
      relating to cancer for South Asian communities was limited. Participants in the
      study expressed a keen desire for this information to be made available via their
      community social networks. This lack of information resulted in low levels of
      awareness about cancer and related issues. Cancer was often perceived as an
      incurable disease, a reflection of the fact that access to appropriate services
      had been experienced at a relatively late stage of the illness. Informed
      education, therefore, is clearly essential to influence how people manage cancer
      and access cancer services. This paper describes the challenges that service
      providers and users face in ensuring effective and informed awareness.

PMID- 15162145
TI  - Combination antiangiogenesis therapy with marimastat, captopril and fragmin in
      patients with advanced cancer.
AB  - Marimastat, low molecular weight heparins and captopril have antiangiogenic
      activity in vitro and in animal models. We studied the safety and efficacy of the
      combination of these drugs in patients with advanced cancer. In all, 50 patients
      were enrolled. Captopril was given orally at a dose of 50 mg bd daily. Fragmin
      was administered as a daily subcutaneous injection of 200 units kg(-1) for the
      first 28 days and 5000 units thereafter. Marimastat was given at 10 mg bd orally.
      Serum, plasma and urinary angiogenic factors were measured at baseline and after
      1 month of treatment. Inhibition of release of tumour necrosis factor alpha (TNF
      alpha) from peripheral lymphocytes was used as a surrogate pharmacodynamic end
      point. There was one case of haemorrhagic stroke and one upper gastrointestinal
      haemorrhage. The commonest toxicity was myalgia. One of 10 patients with renal
      cancer had a partial response, and three patients had a prolonged period of
      stable disease. The treatment significantly inhibited phytohaemagglutinin (PHA)
      stimulated TNF-alpha release from patient's lymphocytes. The combination of
      marimastat, fragmin and captopril is well tolerated and has in vivo activity.
      Inhibition of PHA-stimulated TNF-alpha release from lymphocytes is a surrogate
      pharmacodynamic marker of metalloprotease inhibition.

PMID- 15162148
TI  - Modifying an immunogenic epitope on a therapeutic protein: a step towards an
      improved system for antibody-directed enzyme prodrug therapy (ADEPT).
AB  - Carboxypeptidase G2 (CP) is a bacterial enzyme, which is targeted to tumours by
      an antitumour antibody for local prodrug activation in antibody-directed enzyme
      prodrug therapy (ADEPT). Repeated cycles of ADEPT are desirable but are hampered
      by human antibody response to CP (HACA). To address this, we aimed to identify
      and modify clinically important immunogenic sites on MFECP, a recombinant fusion
      protein of CP with MFE-23, a single chain Fv (scFv) antibody. A discontinuous
      conformational epitope at the C-terminus of the CP previously identified by the
      CM79 scFv antibody (CM79-identified epitope) was chosen for study. Modification
      of MFECP was achieved by mutations of the CM79-identified epitope or by addition
      of a hexahistidine tag (His-tag) to the C-terminus of MFECP, which forms part of
      the epitope. Murine immunisation experiments with modified MFECP showed no
      significant antibody response to the CM79-identified epitope compared to A5CP, an
      unmodified version of CP chemically conjugated to an F(ab)(2) antibody. Success
      of modification was also demonstrated in humans because patients treated with His
      tagged MFECP had a significantly reduced antibody response to the CM79-identified
      epitope, compared to patients given A5CP. Moreover, the polyclonal antibody
      response to CP was delayed in both mice and patients given modified MFECP. This
      increases the prospect of repeated treatment with ADEPT for effective cancer
      treatment.

PMID- 15162149
TI  - High levels of untreated distress and fatigue in cancer patients.
AB  - The purpose of the study was to assess a large representative sample of cancer
      patients on distress levels, common psychosocial problems, and awareness and use
      of psychosocial support services. A total of 3095 patients were assessed over a 4
      week period with the Brief Symptom Inventory-18 (BSI-18), a common problems
      checklist, and on awareness and use of psychosocial resources. Full data was
      available on 2776 patients. On average, patients were 60 years old, Caucasian
      (78.3%), and middle class. Approximately, half were attending for follow-up care.
      Types of cancer varied, with the largest groups being breast (23.5%), prostate
      (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of
      all patients met criteria for general distress in the clinical range. A higher
      proportion of men met case criteria for somatisation, and more women for
      depression. There were no gender differences in anxiety or overall distress
      severity. Minority patients were more likely to be distressed, as were those with
      lower income, cancers other than prostate, and those currently on active
      treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer
      patients were the most distressed. Almost half of all patients who met distress
      criteria had not sought professional psychosocial support nor did they intend to
      in the future. In conclusion, distress is very common in cancer patients across
      diagnoses and across the disease trajectory. Many patients who report high levels
      of distress are not taking advantage of available supportive resources. Barriers
      to such use, and factors predicting distress and use of psychosocial care,
      require further exploration.

PMID- 15162150
TI  - An evaluation of liquid-based cytology and human papillomavirus testing within
      the UK cervical cancer screening programme.
AB  - The aim of this study is to evaluate different options for introducing liquid
      based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical
      cancer screening programme. These include options that incorporate HPV testing
      either as a triage for mild and borderline smear abnormalities or as a primary
      screening test. Outcomes include the predicted impact on resource use, total
      cost, life years and cost-effectiveness. Extensive sensitivity analysis has been
      carried out to explore the importance of the uncertainty associated with disease
      natural history and the impact of screening. Under baseline assumptions, the cost
      effectiveness of different options for introducing LBC appears favourable, and
      these results are consistent under a range of assumptions for its impact on the
      diagnostic effectiveness of cytology. However, if we assume a higher marginal
      cost of LBC in comparison to conventional methods, primary smear testing options
      are predicted to be more cost-effective without LBC. Combined LBC primary smear
      and HPV testing with a 5-year interval is similar in both cost and effectiveness
      to the other 3-yearly options of primary smear testing or primary HPV testing
      alone. However, both primary HPV testing and combined options would give rise to
      a far greater risk of inappropriate colposcopy throughout a woman's lifetime.
      British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884
      www.bjcancer.com Published online 25 May 2004

PMID- 15162151
TI  - A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a
      PAS domain protein.
AB  - Here we report that the OX-TES-1 SEREX antigen, which showed immunological
      reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL)
      patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1
      cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively
      spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the
      first 638 aa of which are common to both proteins. The PASD1-predicted protein
      contains a PAS domain that, together with a putative leucine zipper and nuclear
      localisation signal, suggests it encodes a transcription factor. The expression
      of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while
      PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from
      non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients'
      tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients
      mounting an immune response to PASD1 were of a poor prognosis non-germinal centre
      subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent
      expression was observed in solid tumours (25 out of 68), thus fulfilling the
      criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma
      vaccine development that may also be widely applicable to other tumour types.

PMID- 15162152
TI  - Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer:
      monitoring tumour shrinkage and molecular profile on magnetic resonance and
      assessment of 3-year outcome.
AB  - The objective of this study is to assess tumour response to neoadjuvant
      chemotherapy prior to radical hysterectomy in cervical cancer using magnetic
      resonance (MR) to monitor tumour volume and changes in molecular profile and to
      compare the survival to that of a control group. Eligibility included Stage Ib
      IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in
      22 patients (methotrexate 300 mg x m(-2) (with folinic acid rescue), bleomycin 30
      mg x m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses
      and followed by radical hysterectomy. Post-operative radiotherapy was given in 14
      cases. A total of 23 patients treated either with radical surgery or
      chemoradiotherapy over the same time period comprised the nonrandomised control
      group. MR scans before and after neoadjuvant chemotherapy and in the control
      group documented tumour volume on imaging and metabolites on in vivo
      spectroscopy. Changes were compared using a paired t-test. Survival was
      calculated using the Kaplan-Meier method. There were no significant differences
      between the neoadjuvant chemotherapy and control groups in age (mean, s.d. 43.3+/
      10, 44.7+/-8.5 years, respectively, P=0.63) or tumour volume (medians, quartiles
      35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P=0.068). The
      reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0
      cm(3)) was significant (P=0.002). The reduction in -CH(2) triglyceride approached
      significance (P=0.05), but other metabolites were unchanged. The 3-year survival
      in the chemotherapy group (49.1%) was not significantly different from the
      control group (46%, P=0.94). There is a significant reduction in tumour volume
      and -CH(2) triglyceride levels after neoadjuvant chemotherapy, but there is no
      survival advantage.

PMID- 15162153
TI  - Saliva--a pivotal player in the pathogenesis of oropharyngeal cancer.
AB  - Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most
      common head and neck malignancy and accounts for 2-4% of all new cancers. It is
      primarily induced by exposure to tobacco. The paradigm of cigarette smoke (CS)
      induced OP cancer's pathogenesis is based on the assumption that a constant
      direct attack of various CS carcinogens causes widespread accumulating cellular
      and DNA aberrations in the OP mucosal cells, in turn eventually resulting in
      malignant transformation. However, there is never a direct contact between CS and
      the OP mucosa. Saliva, bathing the mucosa from the oral cavity to the larynx,
      always intervenes, and CS must first interact with saliva before it reaches the
      mucosa. The current study investigated the role of saliva in the pathogenesis of
      OP cancer. A synergistic effect of CS and saliva on oral cancer cells was
      demonstrated. This synergism is based on the reaction between redox active metals
      in saliva and low reactive free radicals in CS, which results in the production
      of highly active hydroxyl free radicals. Thus, when exposed to CS, salivary
      behavior is reversed and the saliva loses its antioxidant capacity and becomes a
      potent pro-oxidant milieu. The devastating role of CS-borne aldehydes was
      demonstrated as well. Based on these results and on our recent reports
      demonstrating that CS destroys various salivary components, including protective
      ones such as peroxidase, the most important salivary antioxidant enzyme, a
      comprehensive view of the pivotal role of saliva in the pathogenesis of CS
      induced OP cancer is suggested.

PMID- 15162154
TI  - Role of nutritional intervention in patients treated with radiotherapy for pelvic
      malignancy.
AB  - Up to 12000 patients with gynaecological, urological and rectal cancer undergo
      radical pelvic radiotherapy annually in the UK. More than 70% develop acute
      inflammatory changes causing gastrointestinal symptoms during treatment because
      healthy bowel tissue is encompassed in the radiation field. In total, 50% go on
      to develop chronic bowel symptoms, which affect quality of life due to permanent
      changes in the small and large intestine. Nutritional intervention may influence
      acute and chronic bowel symptoms but the validity of the advice given to patients
      is not clear. To assess the incidence and significance of malnutrition and to
      examine the efficacy of therapeutic nutritional interventions used to manage
      gastrointestinal side effects in patients undergoing pelvic radiotherapy and
      those with chronic bowel side effects after treatment, a critical review of
      relevant original studies on human subjects was carried out using a specific set
      of mesh terms in MEDLINE and EMBASE databases and the Cochrane Library in
      September 2003. Full texts of all relevant articles were collected and reference
      lists were checked. Sources of grey literature including conference abstracts and
      web-based information were also reviewed. A total of 36 papers published in peer
      reviewed journals between 1966 and 2003 were identified. In all, 14 randomised
      controlled trials, 12 prospective cohorts, four retrospective, two qualitative,
      one validation, one pilot study and two case reports were obtained. These
      included 2646 patients. Eight articles including three conference abstracts and
      web-based information were found. None of the studies was definitive because of
      weakness in methodology. No studies could be combined because the interventions
      and the end points were different. There is no evidence base for the use of
      nutritional interventions to prevent or manage bowel symptoms attributable to
      radiotherapy. Low-fat diets, probiotic supplementation and elemental diet merit
      further investigation.

PMID- 15162155
TI  - Comorbidity has negligible impact on treatment and complications but influences
      survival in breast cancer patients.
AB  - In the present study, we investigated whether age and serious comorbid conditions
      influence treatment decisions, complications and survival in breast cancer
      patients. The Eindhoven Cancer Registry records patient, tumour and therapy
      characteristics of all patients diagnosed with cancer in the southern part of the
      Netherlands. Additional information on severity of comorbidity and serious
      complications was collected for a random sample of 527 breast cancer patients
      (aged 40 years and older). More than 70% of the patients >or=80 exhibited high
      severity of comorbidity compared to 6% of those aged 40-49 years. Treatment was
      not influenced by severity of comorbidity. Less than 30% of the breast cancer
      patients had complications after diagnosis. The number of complications was not
      related to age or severity of comorbidity. The hazard ratio (HR) of dying for
      patients with low/moderate severity of comorbidity was 2.4 for those aged 40-69
      years and 1.6 for those aged >or=70 years, after adjustment for age, nodal status
      and treatment. For patients with high severity of comorbidity, the risk of dying
      was almost three times higher. Older breast cancer patients with serious
      comorbidity were not treated differently and did not have more complications
      compared to those without comorbidity, but they exhibited a worse prognosis.

PMID- 15162156
TI  - Prevalence and management of pain in Italian patients with advanced non-small
      cell lung cancer.
AB  - Pain is a highly distressing symptom for patients with advanced cancer. WHO
      analgesic ladder is widely accepted as a guideline for its treatment. Our aim was
      to describe pain prevalence among patients diagnosed with advanced non-small-cell
      lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain
      management. Data of 1021 Italian patients enrolled in three randomised trials of
      chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13.
      Analgesic consumption during the 3 weeks following QoL assessment was recorded.
      Adequacy of pain management was evaluated by the Pain Management Index (PMI).
      Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe);
      50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3%
      very much). Bone metastases strongly affected presence of pain. Mean global QoL
      linearly decreased from 64.9 to 36.4 from patients without pain to those with
      severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain
      (82%) received inadequate analgesic treatment. Bone metastases were associated
      with improved adequacy and worst pain with reduced adequacy at multivariate
      analysis. In conclusion, pain is common in patients with advanced NSCLC,
      significantly affects QoL, and is frequently undertreated. We recommend that:
      (i). pain self-assessment should be part of oncological clinical practice; (ii).
      pain control should be a primary goal in clinical practice and in clinical
      trials; (iii). physicians should receive more training in pain management; (iv).
      analgesic treatment deserves greater attention in protocols of anticancer
      treatment.

PMID- 15162157
TI  - Telomere shortening and mitotic dysfunction generate cytogenetic heterogeneity in
      a subgroup of renal cell carcinomas.
AB  - Most renal cell carcinomas (RCC) show only simple chromosomal changes. However, a
      more complex cytogenetic pattern has been found in a subgroup of aggressive RCC,
      indicating that further accumulation of chromosome changes could play a role in
      tumour progression. To explore the possible mechanisms behind cytogenetic
      evolution in RCC, a parallel assessment of chromosome mutations and mitotic
      segregation pattern in eight tumours was performed. In the majority of cases, no
      abnormalities in the cell division machinery were found and the rate of
      alterations in chromosome copy number, as measured by interphase FISH, was
      similar to that in non-neoplastic cells. This was reflected by relatively simple
      karyotypes, with little cytogenetic intratumour heterogeneity. In contrast,
      another group of tumours exhibited several cytogenetically related clones with
      additional structural chromosomal changes at two or more ploidy levels and a
      frequency of copy number alterations that was higher than in normal cells. In
      these cases, the telomere repeat sequences were abnormally short and chromosomal
      breakage-fusion-bridge events were observed at cell division, as well as
      multipolar configurations and supernumerary centrosomes. Abnormalities of the
      cell division machinery may thus contribute to the evolution of complex
      karyotypes and genetic intratumour heterogeneity in a subgroup of RCC.

PMID- 15162159
TI  - COX inhibitors and sexual development.

PMID- 15162158
TI  - 5-HT(3A) receptor subunit is required for 5-HT3 antagonist-induced reductions in
      alcohol drinking.
AB  - The ionotropic serotonin subtype-3 (5-HT3) receptor has emerged as a potential
      therapeutic target in the treatment of alcohol abuse and alcoholism because
      selective pharmacological antagonists reduce alcohol consumption in preclinical
      and clinical models. 5-HT binds to the extracellular N-terminus of the 5-HT(3A)
      receptor subunit but receptor activation is also enhanced by distinct allosteric
      sites, which indicates the presence of other receptor subunits. It is not known
      if specific molecular subunits of the 5-HT3 receptor modulate alcohol drinking.
      To address this issue, we characterized acute locomotor response to alcohol and
      alcohol consumption in a two-bottle home-cage procedure by congenic C57BL/6J mice
      with a targeted deletion of the 5-HT(3A) receptor subunit gene. 5-HT(3A)-null
      mice did not differ from wild-type littermate controls on measures of spontaneous
      locomotor activity, habituation to a novel environment, or locomotor response to
      ethanol (0, 0.5, 1, or 2 g/kg). Moreover, null mice did not differ from controls
      on measures of ethanol (2-10%) intake and preference during or after a two-bottle
      home-cage sucrose fading procedure. Systemic administration of the 5-HT3
      antagonist LY-278,584 (0-10 mg/kg) decreased intake of both sweetened (2%
      sucrose+10% ethanol) and unsweetened (10% ethanol) ethanol in wild-type mice
      only. These findings indicate that reduction of alcohol drinking produced by 5
      HT3 antagonism is dependent on the presence of 5-HT(3A)-containing receptors.

PMID- 15162161
TI  - Dendritic arithmetic.

PMID- 15162162
TI  - Deconstructing a navigational neuron.

PMID- 15162163
TI  - Brain gender: prostaglandins have their say.

PMID- 15162164
TI  - A 'landmark' study on the neural basis of navigation.

PMID- 15162165
TI  - Assaying axon sensitivity.

PMID- 15162166
TI  - Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia.
AB  - Schizophrenia is a devastating psychiatric disease that affects 0.5-1% of the
      world's adult population. The hypothesis that this disease is a developmental
      disorder of the nervous system with late onset of its characteristic symptoms has
      been gaining acceptance in past years. However, the anatomical, cellular and
      molecular bases of schizophrenia remain unclear. Numerous studies point to
      alterations in different aspects of brain development as possible causes of
      schizophrenia, including defects in neuronal migration, neurotransmitter receptor
      expression and myelination. Recently, the gene that encodes neuregulin-1 (NRG1)
      has been identified as a potential susceptibility gene for schizophrenia, and
      defects in the expression of erbB3, one of the NRG1 receptors, have been shown to
      occur in the prefrontal cortex of schizophrenic patients, suggesting that NRG1
      erbB signaling is involved in the pathogenesis of schizophrenia. These findings
      open new approaches to defining the molecular and cellular basis of schizophrenia
      in more mechanistic terms.

PMID- 15162167
TI  - A new chemotaxis assay shows the extreme sensitivity of axons to molecular
      gradients.
AB  - Axonal chemotaxis is believed to be important in wiring up the developing and
      regenerating nervous system, but little is known about how axons actually respond
      to molecular gradients. We report a new quantitative assay that allows the long
      term response of axons to gradients of known and controllable shape to be
      examined in a three-dimensional gel. Using this assay, we show that axons may be
      nature's most-sensitive gradient detectors, but this sensitivity exists only
      within a narrow range of ligand concentrations. This assay should also be
      applicable to other biological processes that are controlled by molecular
      gradients, such as cell migration and morphogenesis.

PMID- 15162168
TI  - 13th European Congress on Obesity. Prague, Czech Republic, 26-29 May, 2004.
      Abstracts.

PMID- 15162196
TI  - Management of obesity in adults: project for European primary care.

PMID- 15162198
TI  - Controlled induction of the RpoS regulon in Escherichia coli, using an RpoS
      expressing plasmid.
AB  - RpoS, an alternative sigma factor produced by many gram-negative bacteria,
      primarily controls genes that are expressed in stationary phase in response to
      nutrient deprivation. To test the idea that induction of RpoS in the exponential
      phase, when RpoS is not normally expressed, increases RpoS-dependent gene
      expression, we constructed a plasmid carrying the rpoS gene under the control of
      an IPTG (isopropyl-beta-D-thiogalactopyranoside)-inducible T7lac promoter.
      Northern and Western analyses revealed that levels of RpoS mRNA and protein,
      respectively, increased in response to the inducer IPTG. Assays of changes in
      RpoS-dependent functions (catalase activity and glycogen accumulation), confirmed
      that induced RpoS was functional in exponential phase and was sufficient for the
      expression of RpoS-dependent functions. Controlled expression of RpoS and RpoS
      dependent genes by plasmid-encoded rpoS may thus offer a useful tool for the
      study of RpoS-dependent gene expression.

PMID- 15162199
TI  - Influence of phosphate and disinfection on the composition of biofilms produced
      from drinking water, as measured by fluorescence in situ hybridization.
AB  - Biofilms were grown in annular reactors supplied with drinking water enriched
      with 235 microg C/L. Changes in the biofilms with ageing, disinfection, and
      phosphate treatment were monitored using fluorescence in situ hybridization.
      EUB338, BET42a, GAM42a, and ALF1b probes were used to target most bacteria and
      the alpha (alpha), beta (beta), and gamma (gamma) subclasses of Proteobacteria,
      respectively. The stability of biofilm composition was checked after the onset of
      colonization between T = 42 days and T = 113 days. From 56.0% to 75.9% of the
      cells detected through total direct counts with DAPI (4'-6-diamidino-2
      phenylindole) were also detected with the EUB338 probe, which targets the 16S
      rRNA of most bacteria. Among these cells, 16.9%-24.7% were targeted with the
      BET42a probe, 1.8%-18.3% with the ALF1b probe, and <2.5% with the GAM42a probe.
      Phosphate treatment induced a significant enhancement to the proportion of gamma
      Proteobacteria (detected with the GAM42a probe), a group that contains many
      health-related bacteria. Disinfection with monochloramine for 1 month or chlorine
      for 3 days induced a reduction in the percentage of DAPI-stained cells that
      hybridized with the EUB338 probe (as expressed by percentages of EUB338
      counts/DAPI) and with any of the ALF1b, BET42a, and GAM42a probes. The percentage
      of cells detected by any of the three probes (ALF1b+BET42a+GAM42a) tended to
      decrease, and reached in total less than 30% of the EUB338-hybridized cells.
      Disinfection with chlorine for 7 days induced a reverse shift; an increase in the
      percentage of EUB338 counts targeted by any of these three probes was noted,
      which reached up to 87%. However, it should be noted that the global bacterial
      densities (heterotrophic plate counts and total direct counts) tended to decrease
      over the duration of the experiment. Therefore, those bacteria that could be
      considered to resist 7 days of chlorination constituted a small part of the
      initial biofilm community, up to the point at which the other bacterial groups
      were destroyed by chlorination. The results suggest that there were variations in
      the kinetics of inactivation by disinfectant, depending on the bacterial
      populations involved.

PMID- 15162200
TI  - Biodegradation of Maya crude oil fractions by bacterial strains and a defined
      mixed culture isolated from Cyperus laxus rhizosphere soil in a contaminated
      site.
AB  - Ten bacterial strains were isolated by enrichment culture, using as carbon
      sources either aliphatics or an aromatic-polar mixture. Oxygen uptake rate was
      used as a criterion to determine culture transfer timing at each enrichment
      stage. Biodegradation of aliphatics (10,000 mg L(-1)) and an aromatic-polar
      mixture (5000 mg L(-1), 2:1) was evaluated for each of the bacterial strains and
      for a defined culture made up with a standardized mixture of the isolated
      strains. Degradation of total hydrocarbons (10,000 mg L(-1)) was also determined
      for the defined mixed culture. Five bacterial strains were able to degrade more
      than 50% of the aliphatic fraction. The most extensive biodegradation (74%) was
      obtained with strain Bs 9A, while strains Ps 2AP and UAM 10AP were able to
      degrade up to 15% of the aromatic-polar mixture. The defined mixed culture
      degraded 47% of the aliphatics and 6% of the aromatic-polar mixture. The defined
      mixed culture was able to degrade about 40% of the aliphatic fraction and 26% of
      the aromatic fraction when grown in the presence of total hydrocarbons, while
      these microorganisms did not consume the polar hydrocarbons fraction. The
      proposed strategy that combines enrichment culture together with oxygen uptake
      rate allowed the isolation of bacterial strains that are able to degrade specific
      hydrocarbons fractions at high consumption rates.

PMID- 15162201
TI  - Butyrivibriocin AR10, a new cyclic bacteriocin produced by the ruminal anaerobe
      Butyrivibrio fibrisolvens AR10: characterization of the gene and peptide.
AB  - The gene (bviA) encoding the ruminal bacteriocin butyrivibriocin AR10 was cloned
      from an EcoRI library by using an oligonucleotide probe based on a partial
      peptide sequence of the previously isolated peptide. The gene encoded an 80 amino
      acid prebacteriocin that demonstrated significant identity with the cyclic
      bacteriocin gassericin A. Negative ion time of flight mass spectroscopic analysis
      (ESI/MS) indicated a mass of 5981.5 Da for the isolated bacteriocin, a molecular
      mass that could not be generated by removal of a leader peptide alone. However,
      an N- to C-terminal cyclization of the predicted mature bacteriocin resulted in a
      peptide that conformed to the determined mass and charge characteristics.
      Northern blotting confirmed that expression of bviA mirrored the production of
      the bacteriocin in both liquid and solid media.

PMID- 15162202
TI  - Eight gram-negative bacteria are 10,000 times more sensitive to cationic
      detergents than to anionic detergents.
AB  - In liquid culture, eight typical gram-negative bacteria were ca. 10,000-fold more
      sensitive to cationic detergents than to the anionic detergent sodium dodecyl
      sulfate. Cetyltrimethylammonium bromide (CTAB) was inhibitory at concentrations
      ranging from 0.0006% to 0.01%. Four pseudomonads able to form biofilms were ca.
      1000-fold more resistant to CTAB on Luria-Bertani agar plates than they were in
      liquid culture. A lasI mutant of Pseudomonas aeruginosa was only able to tolerate
      0.1% CTAB on Luria-Bertani agar plates but could tolerate 5% CTAB when
      supplemented with homoserine lactone containing culture supernatants.

PMID- 15162204
TI  - Chemoselectivity in reactions of esterification.
AB  - This review is devoted to the problem of chemoselective formation of ester
      functions in polyfunctional molecules. The review covers most typical approaches
      to chemoselective acylation of hydroxy groups in molecules containing an amino,
      mercapto, or another hydroxy functionality as well as chemoselective
      esterification of di- and polycarboxylic acids.

PMID- 15162203
TI  - Identification of indole-3-acetic acid producing freshwater wetland rhizosphere
      bacteria associated with Juncus effusus L.
AB  - Production of indole-3-acetic acid (IAA), a key physiological feature of
      culturable, O2-tolerant bacteria associated with the freshwater macrophyte Juncus
      effusus L., was examined over a period of 2 years. Up to 74% of rhizobacteria
      identified and tested produced IAA. The number of indoleacetic acid producers
      decreased in winter. IAA was produced even when L-tryptophan, a precursor of IAA,
      was not added to the medium. Most of the IAA-producing strains were dominated by
      strains that were not identifiable to species level on the basis of API testing.
      Based on 16S rRNA gene sequencing and fatty acid analysis, it was found that IAA
      producing rhizosphere bacteria associated with the freshwater wetland plant
      Juncus effusus L. are representatives of several families, including the
      Enterobacteriaceae, Pseudomonadaceae, Aeromonadaceae, Burkholderiaceae, and
      Bacillaceae. This study identifies numerous potentially important bacterial
      physiological groups of freshwater wetlands. Additionally, the study provides a
      baseline for monitoring and assessing the mutualistic relationships of wetland
      plants with rhizosphere bacteria in freshwater wetlands.

PMID- 15162205
TI  - CuI catalyzed N-arylation of amide as a key step for the preparation of 3-aryl
      beta-carbolin-1-ones.
AB  - An expedient synthetic route for 3-aryl beta-carbolin-1-ones was developed
      starting from ethyl acetamidocyanoacetate and chalcone derivatives. The five- and
      six-membered nitrogen-containing rings in the beta-carbolin-1-ones were
      elaborated efficiently by an intramolecular ketone-nitrile annulation and an
      intramolecular N-arylation of amide respectively.

PMID- 15162206
TI  - New phenylselanyl group activation: synthesis of aziridines and oxazolidin-2
      ones.
AB  - After the study of different phenylselanyl group activators, halogenation by N
      bromosuccinimide (NBS) has been shown to be the most suitable manner for
      cyclizing beta-phenylselanyl amines into aziridines and also enabled production
      of oxazolidin-2-ones from N-Boc beta-phenylselanyl amines in excellent yield.

PMID- 15162207
TI  - Observed and calculated 1H- and 13C-NMR chemical shifts of substituted 5H
      pyrido[3,2-a]- and 5H-pyrido[2,3-a]phenoxazin-5-ones and of some 3H-phenoxazin-3
      one derivatives.
AB  - Carbon and proton NMR spectra of several substituted 5H-pyrido[3,2-a]-, 5H
      pyrido[2,3-a]phenoxazin-5-ones and 3H-phenoxazin-3-one derivatives have been
      assigned, and the experimental chemical shifts have been compared with the
      results of density functional calculations employing large basis sets. Solvent
      effects were explored by means of the polarizable continuum method (PCM), while
      the (limited) side-chain flexibility of the compounds has been addressed by
      Boltzmann averaging of the computed spectral parameters over different
      conformational minima. Overall, the calculated shifts reproduce well the
      experiment results; thus, the computational procedure represents a feasible and
      useful complement to multidimensional NMR experiments in the assignment process.

PMID- 15162208
TI  - Calix[4]arenes containing thiourea and amide moieties: neutral receptors towards
      alpha,omega-dicarboxylate anions.
AB  - Two-armed neutral anion receptors (4,5), were prepared and examined for their
      anion-binding ability using UV-vis, fluorescence and 1H NMR spectra in DMSO. The
      results of non-linear curve fitting indicate that 4 or 5 form 1 : 1
      stoichiometric complexes with dicarboxylate anions by multiple hydrogen bonding
      interactions and the sensitivity for recognition of dicarboxylate depends on the
      chain length of these dicarboxylate anions. Receptors 4 and 5 have no binding
      ability with acetate, dihydrogen phosphate and the halogen (Cl-, Br-, I-) anions.
      This demonstrates that receptors 4 or 5 could be used as chemical sensors for
      some special dicarboxylate anions.

PMID- 15162209
TI  - Homoheteroaromaticity: the case study of azepine and dibenzazepine.
AB  - Geometrical and energetic DFT calculations as well as GIAO and NICS chemical
      shifts have been calculated for 1H-azepine and 5H-dibenz[b,f]azepine and their
      cations. The last compound has been studied experimentally by 1H and 13C NMR in
      neutral and acidic conditions establishing that the cation corresponds to an N
      protonated structure. The conclusion is that the neutral molecules are
      antiaromatic while the cations are aromatic (homoheteroaromaticity).

PMID- 15162211
TI  - Synthesis and electrogenerated chemiluminescence of donor-substituted
      phenylquinolinylethynes and phenylisoquinolinylethynes: effect of positional
      isomerism.
AB  - In furtherance of our research on the design, synthesis and study of
      electrogenerated chemiluminescence (ECL) of new donor substituted
      phenylquinolinylethynes, we report here more new series with the aim of studying
      the effect of positional isomerism on their overall photophysical properties with
      a special focus on ECL. For this study we have chosen 2-, 3-, and 4-(p
      substituted phenyl)ethynylquinolines, and 1- and 4-(p-substituted
      phenyl)ethynylisoquinolines. These ethynes were synthesized in good yields by
      modified Sonogashira coupling of the corresponding terminal alkyne with the
      respective haloquinolines. The photophysical properties and ECL were studied in
      acetonitrile solvent and the various results are discussed.

PMID- 15162210
TI  - (1R,4S,5R)-3-Fluoro-1,4,5-trihydroxy-2-cyclohexene-1-carboxylic acid: the fluoro
      analogue of the enolate intermediate in the reaction catalyzed by type II
      dehydroquinases.
AB  - The fluoro analogue of the enolate intermediate in the reaction catalyzed by type
      II dehydroquinases has been prepared from naturally occurring (-)-quinic acid
      over seven steps and has been shown to be the most potent inhibitor reported to
      date of the type II enzyme from Mycobacterium tuberculosis.

PMID- 15162212
TI  - PEG-supported synthesis of pyrazole oligoamides with peptide beta-sheet affinity.
AB  - Pyrazole amino acid oligoamides were prepared on polyethylene glycol starting
      from nitro pyrazole carboxylic acids or protected pyrazole amino acids. The
      polymer support facilitates product isolation during synthesis and makes the
      target oligoamides soluble in chloroform and water. This allows the determination
      of their binding properties towards peptides. Moderate affinity, which increases
      with the number of pyrazole units, is observed in chloroform and water.

PMID- 15162213
TI  - Synthesis of [11C]/(13C)amines via carbonylation followed by reductive amination.
AB  - Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by
      reductive amination. The 11C-carbonylation was performed in the presence of
      tetrakis(triphenylphosphine)palladium using aryl iodides or aryl triflates,
      [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in
      this step were then transformed directly into amines by reductive amination using
      different amines in the presence of TiCl4 and NaBH3CN. The 11C-labelled amines
      were obtained with decay-corrected radiochemical yields in the range 2-78%. The
      radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl
      phenyl-amine was synthesised and analysed by NMR spectroscopy for confirmation of
      the labelling position. Specific radioactivity was determined for the same
      compound. The reference compounds were prepared by reductive amination of ketones
      using conventional reaction conditions and three of the compounds were novel. The
      presented approach is a new method for the synthesis of [11C]/(13C)amines.

PMID- 15162214
TI  - Chemo-enzymatic synthesis of fluorinated 2-N-acetamidosugar nucleotides using UDP
      GlcNAc pyrophosphorylase.
AB  - Two non-natural fluorinated 2-N-acetamidosugar nucleotides, uridine 5'
      diphosphate (UDP) 2-acetamido-2,4-dideoxy-4-fluoro-alpha-D-glucopyranose (UDP-4
      FGlcNAc) 1 and its galacto isomer (UDP-4-FGalNAc) 2, were enzymatically
      constructed by treating chemically synthesized fluorinated 2-N-acetamidosugar 1
      phosphates as the donor with UDP 2-acetamido-2-deoxy-alpha-D-glucopyranose
      pyrophosphorylase in the presence of uridine 5'-triphosphate (UTP).

PMID- 15162215
TI  - Design, synthesis and evaluation of ratiometric probes for hydrogencarbonate
      based on europium emission.
AB  - A series of cationic, zwitterionic and anionic macrocyclic europium complexes has
      been prepared incorporating a N or C- linked acridone chromophore that allows
      sensitisation of Eu emission following excitation at 390-410 nm. Each of these
      complexes selectively binds bicarbonate at physiological pH and reversible
      binding is signalled by a change in the form and relative intensity of the Eu
      emission spectrum. Affinity for bicarbonate is regulated by overall complex
      charge and falls within the range required for intracellular or extracellular
      analyses. Monitoring the ratio of the intensity of Eu emission at up to three
      wavelengths, e.g. 618/588 or 618/702 nm allows the solution concentration of
      bicarbonate to be deduced in a background of competing anions such as lactate,
      citrate and phosphate. Preliminary screens reveal the complexes to be non-toxic
      to NIH-3T3 cells and to be taken inside the cell, encouraging further study.

PMID- 15162216
TI  - Design, synthesis and biological activity of a targeted library of potential
      tryptase inhibitors.
AB  - We have designed, synthesized, and tested two small collections of potential
      tryptase inhibitors. The first library consists of diversely N-substituted 3
      aminopiperidin-2-ones 6, and the second (compounds 7) was prepared by dimerising
      compounds 6 through the 3-amino function using diverse carbon chains. We have
      established efficient routes for obtaining 6 both in solution and on solid
      supports. We have also compared the dimerisation on-resin and in solution. Four
      of the compounds showed a high degree of tryptase inhibition at 1 microM, but
      none surpassed the tryptase inhibition activity of BABIM.

PMID- 15162217
TI  - A practical synthesis of D-erythro-sphingosine using a cross-metathesis approach.
AB  - Starting from a vinylepoxide, a short and practical synthesis of D-erythro
      sphingosine is described. The key transformations are a regioselective opening of
      the vinylepoxide and an E-selective cross-metathesis, affording the target
      molecule 5 in steps and 51% overall yield.

PMID- 15162218
TI  - The energetics of isomeric benzoxazine diones: isatoic anhydride revisited.
AB  - The standard (p(o) = 0.1 MPa) molar enthalpy of formation of crystalline 2H-1,3
      benzoxazine-2,4(3H)dione was measured, at T= 298.15 K, by static bomb calorimetry
      and the standard molar enthalpy of sublimation, at T= 298.15 K, was obtained
      using Calvet microcalorimetry. These values were used to derive the standard
      molar enthalpy of formation in the gaseous phase, T= 298.15 K, of -(401.0 +/-
      3.5) kJ mol(-1). The standard molar enthalpy of sublimation of isatoic anhydride
      was recalculated, and our recommended experimental value for the standard molar
      enthalpy of formation in the gaseous phase, T= 298.15 K, is -(406.2 +/- 3.4) kJ
      mol(-1). Density functional calculations for the two isomers 2H-1,3-benzoxazine
      2,4(3H)dione and isatoic anhydride, in which the ring nitrogen and oxygen have
      been transposed, confirm the experimental evidence of nearly identical
      thermochemical stability for these isomers.

PMID- 15162219
TI  - Natural product based inhibitors of the thioredoxin-thioredoxin reductase system.
AB  - Spiroketal naphthodecalins are readily assembled by Barton's base mediated
      Ullmann binaphthyl ether coupling, Dakin reactions and hypervalent iodine
      spirocyclization. The core structures can be further diversified by enone
      addition and Stille coupling reactions. Nanomolar inhibitors for the Trx/TrxR
      redox control system were prepared by this approach and compared to series of
      natural product isolates. Cytotoxicity in MCF-7 cell assays ranged from an IC50
      of 1.6 to >100 microM.

PMID- 15162221
TI  - Chemoselective thioacetalisation and transthioacetalisation of carbonyl compounds
      catalysed by tetrabutylammonium tribromide (TBATB).
AB  - Thioacetals and thioketals of various aldehydes and ketones were obtained
      directly from carbonyl compounds or by a transthioacetalisation process from
      cyclic O,O-acetals in the presence of dithiols and a catalytic amount of
      tetrabutylammonium tribromide (TBATB). Chemoselective thioacetalisation of
      aromatic aldehydes containing an electron-donating group in the presence of an
      aldehyde containing an electron-withdrawing group, aldehydes in the presence of
      ketones, aliphatic cyclic ketones in the presence of aromatic ketones and less
      hindered ketones in the presence of more hindered ketones have been achieved. A
      cyclic acetal containing an electron-donating group has been chemoselectively
      transthioacetalised in the presence of an acetal having an electron-withdrawing
      substituent. These selectivities are due to the intrinsic reactivity of the
      substrate themselves and are independent of the catalyst and reaction conditions.
      Shorter reaction times, mild reaction conditions, stability of acid sensitive
      protecting groups, high efficiencies, facile isolation of the desired products
      and the catalytic nature of the reagent are the attractive features of the
      present method.

PMID- 15162220
TI  - Synthesis of tricyclic analogues of methyllycaconitine using ring closing
      metathesis to append a B ring to an AE azabicyclic fragment.
AB  - The synthesis of several ABE tricyclic analogues of the alkaloid
      methyllycaconitine 1 is reported. The analogues contain two key pharmacophores: a
      homocholine motif formed from a tertiary N-ethyl amine in a 3
      azabicyclo[3.3.1]nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolidin-1
      ly)benzoate ester 4. The synthesis of the ABE tricyclic analogues of MLA 1 began
      with selective allylation at C-3 of 3 to produce allyl beta-keto ester 4. Double
      Mannich reaction of 4 with ethylamine and formaldehyde produced bicyclic amine 5
      The C-9 ketone of bicyclic amine 5 was selectively reduced to form bicyclic
      alcohols 6 and 7 which were subsequently allylated to form dienes 8 and 9. Ring
      closing metathesis of dienes 8 and 9 afforded tricyclic ethers 11 and 12,
      respectively, the C-8 ester of which was reduced to a hydroxymethyl group to form
      ABE tricyclic analogues 13 and 14. Addition of allylmagnesium bromide to the C-9
      ketone of 20 afforded dienes 21 and 22, which underwent ring closing metathesis
      to form tricyclic esters 23 and 24, respectively. Reduction of the C-8 ethyl
      ester of 23 and 24 to a hydroxymethyl group afforded diols 25 and 26
      respectively. The 2-(3-methyl-2,5-dioxopyrrolin-1-ly)benzoate ester was
      introduced by conversion of alcohols 13, 14, 25 and 26, to the anthranilate
      esters 16, 17, 27 and 28 using N-(trifluoroacetyl)anthranilic acid 15 followed by
      fusion with methylsuccinic anhydride to afford the substituted anthranilates 18,
      19, 29 and 30 containing the key 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate
      ester pharmacophore.

PMID- 15162222
TI  - Enzymatic catalysis of the Diels-Alder reaction in the biosynthesis of natural
      products.
AB  - Recent studies on enzymes catalyzing the Diels- Alder reaction. often named
      "Diels-Alderases", clearlydemonstrated the involvement of this synthetically
      useful reaction in the biosynthesis of natural products.This review covers
      natural Diels-Alder type cycloadducts. synthetic efforts on the chemical
      feasibility ofthe biosynthctic Diels - Alder reaction and a brief history of
      studies on Diels-Alderases. In addition,reaction mechanisms of artificial and
      natural Diels--Alderases are discussed.

PMID- 15162224
TI  - Enzymes in preparative mono- and oligo-saccharide synthesis.
AB  - This review covers advances/developments in the use of enzymes in synthetic mono
      /oligo-saccharide chemistry published in the literature between January 2001 and
      June 2003. Particular attention is paid to the use of aldolases, ketolases,
      glycosidases, glycosynthases, lipases, esterases and coupled multi-enzyme
      biotransformations and 132 references are cited.

PMID- 15162225
TI  - Steroids: reactions and partial synthesis.
AB  - The article reviews the progress in the chemistry of the steroids that was
      published between January and December 2002. The reactions and partial synthesis
      of estrogens, androgens, pregnanes, cholic acid derivatives, cholestanes and
      vitamin D analogues are covered. There are 160 references.

PMID- 15162223
TI  - Natural products active against African trypanosomes: a step towards new drugs.
AB  - This review covers compounds with activity on African trypanosomes (mainly
      Trypanosoma brucei subsp.,T congolense and T vivax) isolated from natural sources
      and is organized according to the structure of the etabolites (alkaloids,
      phenolic derivatives, quinones, terpenes and other metabolites). The literature
      from he mid-1980s up to June 2003 is reviewed and 89 references are cited.

PMID- 15162226
TI  - beta-Phenylethylamines and the isoquinoline alkaloids.
AB  - This review covers beta-phenylethylamines and isoquinoline alkaloids derived from
      them, including further products of oxidation. condensation with formaldehyde and
      rearrangement, some of which do not contain an isoquinoline system, together with
      naphthylisoquinoline alkaloids, which have a different biogenetic origin. The
      occurrence of the alkaloids, with the structures of new bases, together with
      their reactions, syntheses and biological activities are reported. The literature
      from July 2002 to June 2003 is reviewed, with 568 references cited.

PMID- 15162227
TI  - A critical review of the bioavailability of glucosinolates and related compounds.
AB  - Glucosinolates (GLSs) are relatively inert (Z)-N-hydroximinosulfate esters,
      possessing a sulfur-linked beta-D-glucopyranose moiety and a variable side chain,
      found almost exclusively in cruciferous vegetables. Following cell disruption,
      they are hydrolysed by plant myrosinases, forming a group of chemically reactive
      and biologically active compounds. There is considerable evidence that these
      breakdown products, when consumed in the diet, may affect the risk of developing
      chronic diseases. However, in order for any compound to exert an activity in
      vivo, it is necessary to reach the site of action in an appropriate form and
      sufficient concentration. Deleterious and toxic effects may be observed at high
      concentrations: hence, bioavailability is a key factor defining the
      physiological, beneficial dose window of GLS hydrolysis products (GLS-HPs). For
      some GLS-HPs, this window can be rather narrow, and therefore is a critical
      parameter to be considered. In this review we critically evaluate the present
      state of knowledge on all factors that affect bioavailability of GLS-HPs. This
      includes liberation from the plant material, absorption from the digestive
      system, distribution around the body, metabolism and excretion.

PMID- 15162229
TI  - Pelvic endometriosis: US and MRI features.
AB  - Endometriosis represents a common and important clinical problem of women of
      childbearing age. It is a disabling disorder manifesting with pain and
      infertility. The exact pathogenesis of the disease remains unclear, despite the
      different theories that have been formulated. The literature on endometriosis is
      extensive, but often in regard to classic endometrioma. It is surprising that, to
      the best of our knowledge, the many radiologic features of extraovarian
      endometriosis have not been well documented thus far. Although ultrasound (US)
      remains the imaging modality of choice in the radiologic evaluation of female
      patients with pelvic pain, the role of magnetic resonance imaging (MRI) in the
      evaluation of abdominal pain is expanding. In the young patient, MRI may be
      performed if a gynecologic disorder is not suspected at first, especially if US
      findings are equivocal or the abnormality extends beyond the field of view of the
      sonographic probe. Moreover, MRI is useful whenever further characterization of
      pelvic disorder is required. In fact, many causes of pelvic disorders and of
      endometriosis in particular demonstrate characteristic MRI findings. For these
      reasons, in this work we describe the protean US and MRI appearances of
      endometrial foci as encountered in daily experience.

PMID- 15162230
TI  - Gluteal muscular and sciatic nerve metastases in advanced urinary bladder
      carcinoma: case report.
AB  - We present a case of gluteal muscular and sciatic nerve metastases from urinary
      bladder carcinoma. T2-weighted magnetic resonance images demonstrated diffuse
      swelling and an increase in the signal of the right gluteus maximus muscle
      without destruction of the original arrangement of muscular fibers. Further,
      remarkable thickening of the right sciatic nerve showing a relatively hypointense
      signal was detected. Postcontrast T1-weighted images showed strong enhancement of
      these structures. Fine-needle aspiration biopsy with ultrasonographic guidance
      confirmed metastatic carcinoma cells in the right gluteal muscle and the sciatic
      nerve. These radiologic findings may represent a rare pattern of metastasis from
      urinary bladder carcinoma.

PMID- 15162231
TI  - Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in
      pediatric living donor liver transplantation.
AB  - Hepatic arterial thrombosis (HAT) after liver transplantation is a life
      threatening event. Previous reports have suggested that the resistive index (RI)
      of the hepatic artery predicts HAT. Doppler ultrasonography (US) to measure RI,
      however, is not routinely performed. The subjects were 70 pediatric patients who
      underwent living donor liver transplantation (LDLT). Protocol Doppler US was
      performed once or twice a day for 2 weeks postoperatively and 692 records were
      examined. Changes in RI values were examined separately in patients with and
      without HAT complications. The incidence of HAT was 10% (seven of 70). HAT was
      diagnosed an average of 6.2 days after LDLT. In patients without HAT
      complications ( n = 63), average RI levels at 14 days after LDLT were 0.71 +/-
      0.1 (records, n = 625). In patients with HAT complications, RI decreased
      gradually within 2 days before the onset of HAT. RI values of less than 0.6
      predicted HAT within 2 days before onset, with 83% sensitivity and 85%
      specificity. RI during the first 2 weeks after LDLT is a sensitive predictor for
      HAT. Thrombectomy and reanastomosis should be considered when RI values are less
      than 0.6 in Doppler US.

PMID- 15162232
TI  - Activity of Crohn disease: value of Color-Power-Doppler and contrast-enhanced
      ultrasonography.
AB  - Diagnosis and follow-up of Crohn disease (CD) often require invasive instrumental
      examinations, with a high risk of iatrogenic damage. Ultrasound (US) examination
      of bowel walls could be the first choice in managing patients with CD. We
      evaluated the role of tissue color power Doppler (CPD) and B-mode US with
      intravenous injection of contrast medium in the detection of disease activity. In
      our series, 52 patients with CD underwent US examination. Each study was
      completed with tissue CPD and US with intravenous injection of contrast medium
      (Sono Vue) to evaluate intestinal wall vascularization as an index of disease
      activity. We then compared our results with those from clinical and laboratory
      tests and follow-up. Data from US examination with intravenous injection of Sono
      Vue partly agreed with clinical and laboratory tests and CPD in disease activity
      evaluation but were most useful in the follow-up. Bowel US examination associated
      with CPD and in particular US contrast medium injection can be used to detect CD
      activity and modulate therapy and follow-up.

PMID- 15162233
TI  - Multidetector-row CT findings of colonic perforation: direct visualization of
      ruptured colonic wall.
AB  - BACKGROUND: We examined the findings of contrast-enhanced multidetector-row
      computed tomography (MD-CT) in patients with colonic perforation. METHODS:
      Abdominal contrast-enhanced MD-CT findings in six patients with colonic
      perforation were reviewed retrospectively. Patients (three men and three women)
      were 74 to 88 years old (mean age = 78 years). Colonic perforation was confirmed
      by surgery. CT findings were correlated with surgical and pathologic findings.
      RESULT: The site of colonic perforation was suggested by the following
      combination of CT findings: free air, dirty mass, dirty fat sign, extraluminal
      fluid collection, bowel wall thickening, and interruption of colonic wall. The
      ruptured colonic wall was directly visualized in four cases (67%). CONCLUSION:
      Abdominal contrast-enhanced MD-CT may improve the accuracy of diagnosis and
      localization of colonic perforation.

PMID- 15162234
TI  - Transhepatic contemporary palliation of biliary and duodenal stenoses by means of
      metallic stents.
AB  - We describe the treatment of a stenosing lesion of the horizontal duodenum by
      means of a large-bore metallic stent inserted percutaneously in a patient with
      transhepatic biliary drainage. In the same session, we used an expandable
      metallic stent in the biliary tree to relieve jaundice. We recommend the
      transhepatic approach for duodenal metallic stent insertion in patients with
      percutaneous biliary drainage.

PMID- 15162235
TI  - Imaging of neuroendocrine tumors: accuracy of helical CT versus SRS.
AB  - BACKGROUND: We retrospectively compared the accuracy of somatostatin receptor
      scintigraphy (SRS) with that of helical computed tomography (CT) in the detection
      and localization of primary and metastatic neuroendocrine tumors. METHODS: A
      medical record search identified 27 patients with known or clinically suspected
      neuroendocrine tumors who underwent helical CT and SRS within 3 months of one
      another at our institution. CT images were evaluated retrospectively by two
      blinded radiologists who used consensus reading. Images were evaluated for the
      presence or absence of primary tumor and hepatic and extrahepatic metastases. CT
      results were compared with the SRS report as interpreted by the nuclear medicine
      physicians. The results of the surgical, clinical follow-up, and pathologic
      findings were considered as the gold standard. Sensitivity, specificity, and
      accuracy were calculated for both imaging techniques. In addition, McNemar
      analysis was performed to determine statistically significant differences between
      CT and SRS. RESULTS: Helical CT was more sensitive than SRS in the detection of
      extrahepatic metastases, and the difference between the two imaging modalities
      was statistically significant (p = 0.0312) as determined by the McNemar chi
      square test. However, the difference between CT and SRS in detecting primary
      neuroendocrine tumors, hepatic metastasis, and combined hepatic and extrahepatic
      metastasis was not statistically significant (p = 0.625, 1.000, and 1.000,
      respectively). CONCLUSION: Helical CT and SRS have similar sensitivity,
      specificity, and accuracy in detecting primary neuroendocrine tumor and hepatic
      metastasis. However, helical CT appears to be more sensitive in detecting
      extrahepatic metastasis from primary neuroendocrine tumors.

PMID- 15162236
TI  - Incremental value of CT in PET/CT of patients with colorectal carcinoma.
AB  - BACKGROUND: We assessed the contribution of dedicated computed tomographic (CT)
      interpretation to the accuracy of positron emission tomography (PET) plus CT in
      imaging patients with suspected primary or metastatic colorectal carcinoma.
      METHODS: One hundred PET/CT scans in 90 consecutive patients were evaluated
      retrospectively. Imaging was performed on a GE Discovery LS PET/CT scanner. PET
      images were obtained from the skull base through the midthigh after intravenous
      administration of 15 to 20 mCi of [(18)F] fluorine-18-fluoro-2-deoxyglucose.
      Noncontrast axial CT images were obtained at the same anatomic locations, with
      140 kV, 80 mA, 0.8 s/CT rotation, a pitch of 6, and a table speed of 22.5 mm/s.
      The CT component of the PET/CT study was reviewed independently by consensus of
      two blinded readers. Scans were evaluated for the presence of primary disease,
      local recurrence, and distant metastases. Results were compared with the PET/CT
      report. The gold standard was clinical and imaging follow-up for at least 6
      months, surgery, or biopsy. RESULTS: The study included 40 males and 50 females,
      with a mean age of 63 years (range, 31-92 years). The indications for the
      examination were to evaluate for recurrence of colorectal cancer in 83 cases,
      determine disease spread in 15 cases, and evaluate for possible primary
      malignancy in two cases with rising carcinoembryonic antigen. Sensitivity,
      specificity, and accuracy of the PET/CT report and of the combined PET/CT with
      dedicated CT interpretation were 0.914, 0.633, and 0.830 and 0.986, 1.000, and
      0.980, respectively. The difference between PET/CT and the combined PET/CT with
      dedicated CT interpretation with respect to accuracy was statistically
      significant (p < 0.05). CONCLUSION: The CT portion of PET/CT provides valuable
      anatomic and pathologic information to the functional information provided by PET
      and helps improve the overall accuracy of the combined study.

PMID- 15162239
TI  - Laparoscopic flip-flap hernioplasty: an innovative technique for pediatric hernia
      surgery.
AB  - BACKGROUND: Laparoscopic hernia repair is especially advantageous for bilateral
      or recurrent diseases in children because it avoids vas injury. However, it is
      more technically demanding, and the recurrent rate has been higher than with the
      open method. The authors developed a method of laparoscopic hernia repair that is
      easy and secure. METHODS: The hernia opening was repaired with a peritoneal flip
      flap anchored with a single tension-free intracorporeal suture. The vas and
      testicular vessel were completely untouched. The valve mechanism of the flip-flap
      helped to avoid scrotal collection and prevent hernia recurrence. RESULTS: In 32
      patients ages 1 month to 17 years 43 repairs were performed. The early result was
      promising, and no recurrence was noticed in a median follow-up period of 4
      months. CONCLUSIONS: Laparoscopic flip-flap hernioplasty is easy to perform and
      has a number of theoretical advantages, although the long-term result still needs
      to be evaluated.

PMID- 15162237
TI  - Extramedullary hematopoiesis presenting as a focal splenic mass: a case report.
AB  - We report the ultrasound, computed tomographic, and magnetic resonance imaging
      findings in a case of extramedullary hematopoiesis presenting as a focal splenic
      mass in a patient with myelodysplastic syndrome. Ultrasound demonstrated a well
      circumscribed hyperechoic mass, whereas computed tomography showed a
      heterogeneous mass better visualized after administration of intravenous
      contrast. On magnetic resonance imaging, the lesion was hypointense to the spleen
      on T1-weighted images, with increased signal on T2-weighted images, and
      demonstrated enhancement after intravenous contrast administration.
      Extramedullary hematopoiesis should be considered in the differential diagnosis
      for a splenic mass in any patient with a hematologic disorder.

PMID- 15162241
TI  - Bioinformatics: a helpmate in the endoscopic age.

PMID- 15162242
TI  - Sperm characteristics of endurance trained cyclists.
AB  - The purpose of this study was to investigate the influence of cycling on sperm
      characteristics. Twenty subjects volunteered for the study, comprising 10 long
      distance competitive cyclists (median 25.5 y) and 10 sedentary controls (median
      24.5 y). A questionnaire was used to obtain a history of training, health,
      nutrition and life style. Semen analysis consisted of a detailed evaluation of
      sperm characteristics that included semen volume, sperm count, viability,
      motility and morphology. Compared to controls, the cyclists had a significantly
      lower proportion of spermatozoa with normal morphology (medians: 41.5 % versus
      19.5 %; p < 0.01) and a significantly higher proportion of morphologically
      abnormal tapered forms (medians: 4.5 % versus 22.5 %; p < 0.01). No significant
      difference in semen volume and sperm motility, viability and count was observed
      between the two groups. We concluded that endurance cycling appears to be
      associated with a significant alteration in sperm morphology.

PMID- 15162240
TI  - Optimal management of the morbidly obese patient. SAGES appropriateness
      conference statement.
AB  - BACKGROUND: Obesity is a growing health problem that contributes to numerous life
      threatening or disabling disorders, including coronary artery disease,
      hypertension, type 2 diabetes mellitus, hyperlipidemia, degenerative joint
      disease, and obstructive sleep apnea. Significant weight reduction in the
      morbidly obese improves or reverses associated illness and benefits well-being.
      The purpose of the SAGES Appropriateness Conference was to summarize the state of
      the art for open and laparoscopic operations for the morbidly obese. METHODS: The
      English literature comparing bariatric procedures was reviewed and grouped by
      level of evidence by three surgeons (BS, LV, and CC). From more than 1,500
      articles, all conference participants were provided with reprints and table
      summaries of no less than 50 selected manuscripts. Ten experts were requested to
      present reviews and make evidence-based arguments for and against the open and
      laparoscopic approaches in written format. An expert panel of six surgeons,
      including an ethicist and patient, commented on implications of data presented.
      The finalized statement was e-mailed to all participants for approval and
      comment. RESULTS: Consensus statements were achieved on various aspects of morbid
      obesity, including indications for surgery, resolution of comorbid illnesses with
      significant weight loss, and the importance of committed bariatric program. Our
      panel of experts agreed, in general, to the advantages of laparoscopic approaches
      compared to open operations in skilled hands. CONCLUSIONS: Laparoscopic Roux-en-Y
      gastric bypass (RYGB) affords improved short-term recovery compared to open
      gastric bypass. Laparoscopic adjustable banding can be performed with lower
      average mortality than either RYGB or any of the malabsorptive operations, and it
      produces variable degrees of short-term weight loss. Prospective randomized
      trials are needed to compare gastric bypass, malabsorptive, and restrictive
      procedures.

PMID- 15162243
TI  - Attenuated ANF response to exercise in athletes with exercise-induced hypoxemia.
AB  - Some highly trained endurance athletes develop an exercise-induced hypoxemia
      (EIH) at least partially due to a hemodynamic factor with a potential stress
      failure on pulmonary capillaries. Atrial natriuretic factor (ANF) is a pulmonary
      vasodilatator and its release during exercise could be reduced with endurance
      training. We hypothesized that athletes exhibiting EIH, who have a greater
      training volume than non-EIH athletes, have a reduced ANF release during exercise
      explaining the pathophysiology of EIH. Ten highly trained EIH-athletes (HT-EIH),
      ten without EIH (HT-nEIH), and nine untrained (UT) males performed incremental
      exercise to exhaustion. No between group differences occurred in resting ANF
      plasma levels. In contrast to HT-nEIH and UT (p < 0.05), HT-EIH showed a smaller
      increase in ANF concentration between rest and maximal exercise (HT-EIH: 8.12 +/-
      0.69 vs. 14.1 +/- 1.86 pmol x l (-1); HT-nEIH: 10.46 +/- 1 vs. 18.7 +/- 1.8 pmol
      x l (-1); UT: 6.23 +/- 0.95 vs. 20.38 +/- 2.79 pmol x l (-1)). During the
      recovery, ANF levels decreased significantly in HT-nEIH and UT groups (p < 0.05).
      Electrolyte values increased in all groups during exercise but were higher in
      both trained groups. In conclusion, this study suggested that ANF response to
      exercise may be important for exercise-induced hypoxemia.

PMID- 15162244
TI  - Concomitant abuse of anabolic androgenic steroids and human chorionic
      gonadotrophin impairs spermatogenesis in power athletes.
AB  - Abuse of anabolic androgenic steroids (AASs) may be an aetiological factor in
      male infertility among recreational power athletes. They try to avoid AAS-induced
      deterioration in spermatogenesis by combining doses of human chorionic
      gonadotrophin (HCG) and/or antiestrogens with their AAS abuse. Eighteen healthy
      male power athletes using massive doses of AASs were recruited for the study.
      Semen samples were collected during AAS abuse and 1.5 and 6 months after
      cessation of the abuse. They were also asked about their reproductive activity
      six years after the study. At the end of the AAS cycle, the sperm count was 33 +/
      49 x 10 (6) /ml (mean +/- SD), and only one subject had azoospermia. At 1.5
      months after cessation of the AAS cycles, the mean sperm concentration was 30 +/-
      42 x 10 (6) /ml, and after six months 77 +/- 70 x 10 (6) /ml. There were
      significant differences between the sample drawn six months after cessation of
      AAS abuse and both samples drawn during and 1.5 months after the abuse (p </=
      0.05, repeated measures of ANOVA). There was a significant positive correlation
      between HCG dose during the cycle and the relative amount of morphologically
      abnormal spermatozoa (r = 0.60, p < 0.01). The concomitant abuse of HCG and
      supraphysiological AAS dose cause transient impairment on semen quality in males,
      although spermatogenesis is maintained with this regimen despite prolonged abuse
      of massive doses of AAS.

PMID- 15162245
TI  - Effect of acute hypoxia on heart rate variability at rest and during exercise.
AB  - The purpose of this study was to investigate sympathovagal balance as inferred
      from heart rate variability (HRV) responses to acute hypoxia at rest and during
      exercise. HRV was evaluated in 12 healthy subjects during a standardized hypoxic
      tolerance test which consists of four periods alternating rest and moderate
      exercise (50 % V.O (2)max) in normoxic and hypoxic conditions. Ventilatory
      responses were determined and HRV indexes were calculated for the last 5 min of
      each period. In well-tolerant subjects, hypoxia at rest induced a decrease of
      root-mean-square of successive normal R-R interval differences (RMSSD) (p < 0.05)
      and of absolute high frequency (HF) power (p < 0.001). All absolute HRV indexes
      were strongly reduced during exercise (p < 0.001) with no further changes under
      the additional stimulus of hypoxia. A significant increase (p < 0.05) in the
      HF/(LF+HF) ratio (where LF is low frequency power) was found during exercise in
      hypoxia compared to exercise in normoxia, associated with similar mean changes in
      ventilation and tidal volume. These results indicate a vagal control withdrawal
      under hypoxia at rest. During exercise at 50 % V.O (2)max, HRV indexes cannot
      adequately represent cardiac autonomic adaptation to acute hypoxia, or possibly
      to other additional stimuli, due to the dominant effect of exercise and the
      eventual influence of confounding factors.

PMID- 15162246
TI  - Influence of aerobic fitness level on measured and estimated perceived exertion
      during exhausting runs.
AB  - The purpose of the present investigation was 1) to study the effects of fitness
      level on perceived exertion (RPE) and estimated time limit (ETL) scales during
      exhausting runs, and 2) to predict time to exhaustion from RPE or ETL values
      collected during a constant run exercise. Eight high-fitness level and twelve
      moderate-fitness level endurance trained males performed two exhausting exercises
      on a 400-m running track. The first test was a graded exercise using a portable
      metabolic system to determine maximal oxygen uptake (V.O (2)max), the velocity
      associated with V.O (2)max (vV.O (2)max), the velocity at the lactate threshold
      (vLT) and the velocity at delta 50 (vDelta50 : the velocity halfway between vV.O
      (2)max and vLT). The second test was a constant run exercise at vDelta50 to
      determine the time to exhaustion at this intensity (tlimvDelta50). Moderate
      fitness level athletes perceived exercise to be relatively more strenuous and
      felt that they could continue for less time than high-fitness level athletes at
      similar relative velocities. There was no effect of fitness level on perceived
      exertion for a given relative exercise duration. RPE corresponding to vLT was not
      statistically significantly different between the two levels groups. For the two
      groups, measured and predicted exhaustion time values, which were calculated from
      linear extrapolation of RPE and ETL values collected during the first 4 minutes
      of a submaximal constant run exercise, were not statistically significantly
      correlated. These results indicate that the aerobic fitness level seems to
      influence perceived exertion only during graded exercise. Consequently, if RPE is
      used to prescribe an exercise intensity, the prescription must be individualised
      regarding the aerobic fitness level of the athlete except for exercise
      intensities corresponding to vLT. Moreover, the perceived exertion pattern at the
      beginning of a submaximal constant run exercise could not be considered as a
      sensitive predictor of the point of self-imposed exhaustion whatever the fitness
      level of the athletes.

PMID- 15162247
TI  - Specific effects of eccentric training on muscular fatigability.
AB  - This study was designed to test the hypothesis that an eccentric training period
      induces a reduction of neuromuscular fatigability following an eccentric
      exercise. Before (Pre-T) and after (Post-T) a 7-wks sub-maximal eccentric
      training, ten active males performed a fatiguing exercise consisting of five sets
      of ten maximal eccentric elbow flexions. Before (Pre-T-1 and Post-T-1) and after
      (Pre-T-2 and Post-T-2) each fatiguing exercise, the voluntary torque and its
      associated agonistic electromyographic activity (RMS), assessed at four angular
      velocities (-60 degrees x s (-1); 0 degrees x s (-1); 60 degrees x s (-1); 240
      degrees x s (-1)) were measured. The isometric voluntary activation level and
      twitch contractile properties were measured. The training period induced
      significant eccentric and isometric torque gains. While isometric and concentric
      torque decreases were similar Pre-T-2 and Post-T-2, the eccentric torque loss was
      significantly lower Post-T-2 than Pre-T-2 (-11.7 +/- 10.2 % and -20.5 +/- 6.5 %,
      respectively; p < 0.05). The reduction of the twitch maximal rate of torque rise
      was also significantly lower Post-T-2 (-49.4 +/- 11.9 %) than Pre-T-2 (-65.2 +/-
      9.8 %) (p < 0.05). The loss of maximal voluntary activation and RMS were similar
      Pre-T-2 and Post-T-2. The present experiment showed that a 7-wks eccentric
      training period produced contraction-type specific adaptations that significantly
      reduced the exercise-induced torque loss during eccentric muscle actions.

PMID- 15162248
TI  - Respiratory muscle training in healthy humans: resolving the controversy.
AB  - Specific respiratory muscle training offers the promise of improved exercise
      tolerance and athletic performance for a wide range of users. However, the
      literature addressing respiratory muscle training in healthy people remains
      controversial. Studies into the effect of respiratory muscle training upon whole
      body exercise performance have used at least one of the following modes of
      training: voluntary isocapnic hyperpnea, flow resistive loading, and pressure
      threshold loading. Each of these training modes has the potential to improve
      specific aspects of respiratory muscle function. Some studies have demonstrated
      significant improvements in either time to exhaustion or time trial performance,
      whilst others have demonstrated no effect. We present an overview of the
      literature that rationalizes its contradictory findings. Retrospective analysis
      of the literature suggests that methodological factors have played a crucial role
      in the outcome of respiratory muscle training studies. We conclude that in most
      well controlled and rigorously designed studies, utilizing appropriate outcome
      measures, respiratory muscle training has a positive influence upon exercise
      performance. The mechanisms by which respiratory muscle training improves
      exercise performance are unclear. Putative mechanisms include a delay of
      respiratory muscle fatigue, a redistribution of blood flow from respiratory to
      locomotor muscles, and a decrease in the perceptions of respiratory and limb
      discomfort.

PMID- 15162249
TI  - Workload demands in mountain bike racing.
AB  - This study aims at describing the workload demands during mountain bike races
      using direct power measurements, and to compare these data to power output and
      physiological findings from laboratory exercise tests. Power output (P, Watt)
      from 11 national team cyclists (9 male, 2 female) was registered continuously
      during 15 races using mobile crank dynamometers (SRM System). To evaluate the
      intensity of racing, incremental exercise tests with determination of P at
      aerobic and anaerobic thresholds (AT, IAT) and at exhaustion (MAX) were
      performed. Intensity zones were determined (zone 1 < AT; AT < zone 2 < IAT; IAT <
      zone 3 < MAX; zone 4 > MAX) and time spent during racing in these zones was
      calculated. Based on power output measurements P during racing was 246 +/- 12 W
      (male) and 193 +/- 1 W (female). P showed high variation throughout the race. In
      contrast heart rate (HR) was relatively stable during racing (male 177 +/- 6 bpm,
      female 172 +/- 7 bpm). 39 +/- 6 % of race time were spent in zone 1, 19 +/- 6 %
      in zone 2, 20 +/- 3 % in zone 3 and 22 +/- 6 % in zone 4. MTB races are
      characterized by a high oscillation in P with permanently elevated HR. A highly
      developed aerobic and anaerobic system is needed to sustain the high variation in
      workload.

PMID- 15162250
TI  - Colour and power Doppler sonography in symptomatic Achilles tendon disease.
AB  - The present trial focused on the exact role of colour and power Doppler
      sonography in Achilles tendinopathy and correlated these techniques with the
      clinical severity of the disease and with findings on grey-scale sonography.
      Twenty patients with in total 28 symptomatic Achilles tendons were included in
      this prospective trial. Additionally included were the asymptomatic tendons (n =
      12) of patients and both tendons (n = 30) of fifteen controls. The pain score of
      Robinson - which ranges from 0 (strong severe pain) to 100 (asymptomatic) - was
      used to assess clinical severity of the disease. Both tendons of patients and
      controls were examined by a GE LOGIQ 9 trade mark scanner with a small-parts 14
      MHz transducer. Grey-scale sonography detected in total 31 focal hypoechoic areas
      in 19 (68 %) of the 28 symptomatic tendons. Colour as well as power Doppler
      sonography detected blood flow in 14 (74 %) of the 19 tendons with focal
      hypoechoic areas. No blood flow was detected in the remaining symptomatic tendons
      (n = 14) and in the asymptomatic tendons of patients or in both tendons of
      controls. Colour and power Doppler sonography resulted in a specificity of 100 %
      and a sensitivity of 50 % for symptomatic Achilles tendinopathy. Patients with
      blood flow within the tendon had a significantly lower score according to
      Robinson than symptomatic patients without flow (P = 0.009). It is concluded that
      colour and/or power Doppler sonography are useful as an adjunct to grey-scale
      sonography in the examination of Achilles tendinosis, especially because the
      presence of blood flow is associated with stronger pain, discomfort and physical
      restriction.

PMID- 15162251
TI  - Effects of iron intake through food or supplement on iron status and performance
      of healthy adolescent swimmers during a training season.
AB  - Maintenance of a normal iron status is important for swimming performance during
      training and competition. The purpose of this study was to investigate whether 1)
      the iron status of healthy adolescent swimmers changes during a training season
      of six months, and 2) increasing daily iron intake affects iron status or
      performance. Forty-two (21 male and 21 female) swimmers, aged 12 - 17, without
      anemia or iron deficiency were divided into three equal groups. Group A received
      an iron supplement of 47 mg per day, group B followed a dietary plan rich in iron
      (providing, on average, 26 mg per day), and group C had a regular diet. Blood
      samples were taken before the beginning of the study and at the end of each of
      three training phases (moderate intensity training, high intensity training, and
      tapering) for the determination of hematological and iron status parameters. To
      evaluate performance, swimming tests at different distances were conducted along
      with blood sampling. The results showed significant fluctuations of iron status
      during the training season, including an increase in erythrocyte parameters
      during moderate intensity training. No significant differences in iron status or
      performance were found among the three groups. In conclusion, iron status and
      performance of healthy adolescent swimmers were affected by training irrespective
      of iron intake ranging from one to over five times the RDA over a period of six
      months.

PMID- 15162253
TI  - [Therapy of idiopathic pulmonary fibrosis - what remains?].

PMID- 15162252
TI  - Trait anxiety predicts panic behavior in beginning scuba students.
AB  - Recreational scuba diving is associated with a significant number of fatalities
      and decompression illnesses each year, and there is evidence that permanent
      neuropsychological injury can occur in divers. There is also evidence that the
      principal cause of decompression illness and fatalities in divers is rapid
      ascent, and it appears that the primary stimulus for rapid ascent is panic. The
      primary purpose of this investigation was to evaluate the extent to which an
      objective measure of trait anxiety could be effective in predicting panic
      behavior in students undergoing scuba training. Trait anxiety was assessed at the
      outset of scuba instruction in 42 students, and the instructor recorded instances
      of panic behavior during the 4-month course. It was predicted that individuals
      scoring 39 or greater on the trait anxiety sub-scale of the State-Trait Anxiety
      Inventory would be more likely to experience panic behavior than individuals with
      scores below this cut-off. Predictions and actual recordings of panic behavior
      were performed independently using a blinded paradigm. Eleven of the students
      exhibited panic behavior on two or more occasions during the instruction, and 35
      of 42 (83 %) predictions were accurate (p < 0.001). It is concluded that an
      objective measure of trait anxiety can be employed a priori for prediction of
      panic behavior in beginning scuba students.

PMID- 15162254
TI  - [Immunohistochemical localization of matrix metalloproteinases (MMP) and tissue
      inhibitors of metalloproteinases (TIMP) in tuberculous pleuritis].
AB  - Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases
      (TIMP) have been found by ELISA and gelatine zymography in different
      concentrations in pleural fluid in tuberculous (TB) pleuritis. For further
      differentiation MMP and TIMP were localized in pleural biopsies by
      immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3,
      MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB).
      Immunohistological reactivity of MMP-1 was found in epitheloidcellular
      histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in
      fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid
      cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly
      positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts,
      epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial
      cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The
      observed inhomogenous staining pattern could be explained by the different state
      of activation of individual cellular units. In conclusion, the
      immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue
      structures indicates their local involvement in fibrosing reactions in TB
      pleuritis.

PMID- 15162256
TI  - [Paraneoplastic limbic encephalitis in small cell lung carcinoma].
AB  - We report about a 63-year-old male patient who complained of a recent onset of
      confusion. A mediastinal mass had been detected in his chest X-ray three days
      before admission to our clinic. Surprisingly, a CT scan of the brain revealed no
      signs of cerebral masses or oedema. MRI demonstrated bright hyperintens signals
      in the medial aspect of both temporal lobes. Biopsy by mediastinoscopy showed
      small cell lung carcinoma (SCLC). No distant metastases were found by staging
      procedures. Cerebrospinal fluid and serum contained antineuronal antibodies (anti
      Hu). The combination of symptoms, MRI findings and paraneoplastic antibodies
      established the diagnosis of paraneoplastic limbic encephalitis in a patient with
      SCLC. Chemotherapy combined with immunosuppression by corticosteroids was started
      immediately. The primary tumour responded to therapy but improvement of cerebral
      symptoms was unsatisfactory. Severe memory loss and personality changes remained
      unchanged while there was a slight improvement in confusion and hallucinations.

PMID- 15162258
TI  - [The sleep apnoea syndromes: alternative therapies].
AB  - Weight-loss recommendation, no alcohol and no sedatives are the first therapeutic
      approaches for patients with the obstructive sleep apne syndrome. However,
      further steps are often necessary. If there is a postural component in mild cases
      sleeping on the side can help. Recent developments are a range of operations that
      increase the size of the pharynx. There is a good relief in snoring but the
      reduction in apnea rate is less successful. Oral appliances are are indicated for
      primary snoring or mild obstructive sleep apnea. The are no data that support the
      use of drugs as a therapy for obstructive sleep apnea. Different nonprescription
      therapies are available (internal and external nasal dilators, nasal and oral
      lubricants, dietary supplements, magnetic pillows and matresses) but their
      usefulness for the treatment has not been demonstrated. The treatment of choice
      for sleep-related obstructive breathing disorders is nCPAP.

PMID- 15162257
TI  - [COPD: an inflammatory disease of the airways?].
AB  - COPD is characterized by a not fully reversible airflow limitation which is
      progressive and associated with an abnormal inflammatory reaction of the lungs.
      Airflow limitation is most often assessed by FEV (1.0). However, FEV (1.0) does
      not always reflect the course of the disease and does not appropriately describe
      the functional effect of a pharmacological or non-pharmacological intervention.
      Measurement of inspiratory parameters, e.g. IC or FIV (1.0), as well as
      assessment of exercise capacity should therefore be part of functional tests. The
      abnormal inflammatory reaction of the lungs can be assessed by a variety of
      methods. However, the characteristic increase of the number of neutrophils does
      not indicate a new therapeutic target. The term abnormal inflammation of the
      airways in bronchial asthma as well as in COPD presumably prompted a number of
      studies investigating the effects of inhalative corticosteroids in COPD. ICS do
      not alter the course of the disease, however they may reduce the number and
      severity of exacerbations. Combination of long-acting beta -agonists and ICS
      exert a better effect than either compound alone. This beneficial effect is
      difficult to explain by an anti-inflammatory action, as the long acting
      anticholinergic tiotropium has a comparable symptomatic and functional effect and
      reduces exacerbations without any known anti-inflammatory component. Future
      pharmacological therapies should therefore be based on a better understanding of
      the functional consequences of the disease and its pathogenesis.

PMID- 15162255
TI  - [Isolation measurements for cystic fibrosis patients].
AB  - BACKGROUND: Respiratory tract infections significantly contribute to morbidity
      and mortality of cystic fibrosis patients. METHODS: We conducted a systematic
      literature review (Pubmed 01/1966 up to 09/2003) in order to present
      recommendations for the isolation of CF patients colonized with Burkholderia
      cepacia spp., Pseudomonas aeruginosa, Stenotrophomonas maltophilia and
      Alcaligenes spp. Evidence and quality of 64 publications dealing with pathogen
      transmission or isolation measurements of colonized patients were evaluated.
      RESULTS: B. cepacia spp. was dealt most often with and 35 of 36 authors
      recommended the isolation of patients colonized with this pathogen. Isolation of
      patients colonized with P. aeruginosa was proposed by 21 of 25 authors. Only 5
      studies concerned S. maltophilia or Alcaligenes spp. CONCLUSIONS: A) B. cepacia
      spp. colonized patients need to get a single room for their own. B) P. aeruginosa
      colonized CF patients should be separated from non-colonized CF patients. C)
      Patients harbouring even multi drug resistant P. aeruginosa, S. maltophilia or
      Alcaligenes spp. may not share their room with immunocompromised patients and
      should also be isolated when treated in intensive care units.

PMID- 15162259
TI  - [Vasoactive intestinal polypeptide in the respiratory tract: physiology and
      pathophysiology].
AB  - Peptidergic neuromediators have gained importance in the field of respiratory
      physiology and pathophysiology due to the characterisation of numerous pulmonary
      effects in the past years. With regard to the multitude of mediators, the
      neuropeptide vasoactive intestinale polypeptide (VIP) plays a special role as it
      exerts potent anti-inflammatory and immunomodulatory effects.
      Neurophysiologically the peptide has been attributed to the family of the
      inhibitory non-adrenergic non-cholinergic (i-NANC) neuromediators of the
      pulmonary innervation. VIP-containing nerve fibres are localized in the airway
      and vascular smooth muscle layers of trachea and bronchi in the human respiratory
      tract. Apart from strong vasodilatory effects, the peptide also shows a high
      bronchodilatory potency. In a large number of respiratory diseases VIP may play a
      pathophysiological role. In this respect, increased levels of VIP have been
      demonstrated for inflammatory diseases of the upper and lower airways and the
      peptide may also play a role in pulmonary hypertension. Due to its fast enzymatic
      cleavage, VIP-based therapies have not been used in routine therapy so far. Also,
      the use of synthetic VIP-agonists did not lead to an improved outcome in patients
      with bronchial asthma if compared to classical drugs. However, recent data from
      animal experiments indicate potent immunomodulatory effects which suggest a
      future use of this mediator and its agonists in the therapy of immune diseases.

PMID- 15162260
TI  - [Amyloidoses of the lung].

PMID- 15162261
TI  - [Amyloidoses of the lung].

PMID- 15162263
TI  - [New documentation sheet for medical examination due to exposures to dust].
AB  - With beginning of the year 2004 a new documentation sheet for occupational
      preventive medical examinations according to exposures to mineral dust (quartz,
      asbestos, ceramic fibres) will replace the existing sheet. The new investigation
      sheet is presented in this publication and changes are described.

PMID- 15162262
TI  - [Recommendations for quality standards in bronchoscopy].

PMID- 15162264
TI  - [Reduced earning capacity due to IgE-mediated skin and airway allergy. Consensus
      paper].

PMID- 15162266
TI  - [Decompensated strabismus surso-adductorius].
AB  - Strabismus surso-adductorius is a frequent unilateral or bilateral eye movement
      disorder. Its clinical features include eye elevation with concomitant vertical
      deviation in adduction, an abnormal head posture from which the patient is
      unaware (head turned and tilted towards the healthy side), a moderate subjective
      excyclotorsion, and a positive Bielschowsky head tilt test. Despite its anglo
      saxon denomination as "congenital fourth nerve palsy", it is not a paretic
      disorder. Strabismus surso-adductorius differs from fourth nerve palsy both by
      etiology and by symptoms. A proper diagnosis is important as neuroradiological
      examination is mandatory in cases of acquired non-traumatic fourth nerve palsy,
      whereas decompensated strabismus surso-adductorius can be operated on without any
      further investigations. Early on, the oculomotor disorder is often well
      compensated and it does manifest at the adult age. Asthenopia and intermittent
      vertical diplopia appear as the fusional mechanisms fade out. The best surgical
      technique for strabismus surso-adductorius is an inferior oblique weakening
      procedure. In severe cases a combined shortening of the superior oblique tendon
      may be necessary.

PMID- 15162267
TI  - [First experience with amniotic membrane transplantation].
AB  - BACKGROUND: The purpose of this retrospective study was to analyze the outcome of
      amniotic membrane transplantation (AMT) performed at the University Eye Clinic
      Bern during the last 12 months. PATIENTS AND METHODS: Nine men (62.4 +/- 16.7
      yrs.) and four women (78.3 +/- 22.3 yrs.) were treated with an AMT and grouped
      according to the ophthalmologic diagnosis: Group A, chronic corneal surface
      defect without limbal stem cell deficiency (n = 8); Group B, conjunctival fornix
      reconstruction (n = 7); Group C, filtering bleb defect (n = 2). RESULTS: 11/17
      (65 %) AMT's performed in 14 eyes of 13 patients showed a favorable postoperative
      result after a mean follow-up time of 8.7 (+/- 2.9) months. In Group A (chronic
      corneal surface defect) 4/8, in Group B (conjunctival fornix defect) 7/7 and in
      Group C (filtering bleb defect) 0/2 showed an improvement of the basic ocular
      problem. 4/8 patients from Group A and 7/7 patients of Group B showed
      postoperatively a strong reduction of the ocular inflammation. CONCLUSIONS: In
      the present small study, favorable results were achieved in patients with chronic
      corneal surface defects without limbal stem cell deficiency and conjunctival
      fornix defects following AMT. In patients with fornix defects, the AMT seemed to
      be a valuable alternative to the more complicated transplantation of mouth- or
      nose mucous membrane. The two eyes with filtering defects failed.

PMID- 15162269
TI  - Corneal and retinal temperatures under various ambient conditions: a model and
      experimental approach.
AB  - BACKGROUND: To determine the distribution of temperatures between the cornea and
      retina under various external conditions, such as illumination and external
      temperature, using a simplified heat exchange model. MATERIALS AND METHODS: The
      human eye is modeled as a water sphere surrounded by different heat sources:
      choroidal and ciliary body blood flow, tears evaporation, metabolic activity,
      diffuse retinal illumination and external convection. Corneal and retinal
      temperatures are derived from this model using finite element theory applied to
      heat transport. Each of five subjects (28 +/- 10 years old) were placed in three
      different environments: - 20 degrees C, 20 degrees C and 40 degrees C. After 15
      mn, their corneal temperatures were measured with an infrared camera. Corneal
      temperatures are compared with the values obtained from the model, assuming the
      same blood flow for all environments. RESULTS: 1) Ciliary body and choroid
      contribute at least 20 times more than retina to the retinal temperature; 2)
      temperature increase of the retina due to illumination is negligible; 3) a 10 %
      reduction of choroidal blood flow induces a corneal temperature decrease of 0.2
      degrees C at - 20 degrees C and < 0.1 degrees C at 20 degrees C and 40 degrees C.
      At normal choroidal blood flow, changes in ambient temperature have a negligible
      effect on retinal temperature. Measured corneal temperatures agreed with the
      values from the model: 26.4 +/- 0.9 versus 26.8 degrees C, at - 20 degrees C and
      36.2 +/- 0.5 versus 36.7 at 40 degrees C. CONCLUSIONS: Our simplified eye model
      predicts in a satisfactory way measured corneal temperatures under very different
      conditions. Calculations show that changing external temperatures from - 20 to +
      40 degrees C affects the retinal temperature by less than 1.8 degrees C.

PMID- 15162270
TI  - [Capsular bag distention after implantation of foldable acrylic lenses].
AB  - BACKGROUND: Incomplete removal of the viscoelastic material during cataract
      surgery may lead to the early postoperative capsular block syndrome. In this
      retrospective case series, postoperative capsular bag distention after
      implantation of a foldable acrylic lens is reported and the sequelae are
      analyzed. PATIENTS AND METHOD: In a retrospective case series, 10 eyes of
      altogether 1674 eyes that underwent cataract surgery in the years 2001 and 2002
      were identified with early postoperative capsular block syndrome. All 10 eyes had
      cataract removal with continuous curvilinear capsulorhexis, phacoemulsification
      and a foldable acrylic lens was placed in the capsular bag. In 4 of 10 eyes
      cataract extraction was combined with trabeculectomy. All patients had posterior
      Nd:YAG capsulotomy. Refraction was performed before and after capsulotomy.
      RESULTS: Postoperative examination showed capsular bag distention in all eyes.
      The mean postoperative spherical equivalent was -3.9 +/- 1.6 Dpt. As the target
      refraction was -1.2 +/- 1.0 Dpt there was an average of -2.7 +/- 1.4 Dpt of
      induced myopia. A mild increase in postoperative anterior chamber inflammation
      was noted only in 1 patient and shallowing of the anterior chamber was observed
      in another patient. Posterior Nd:YAG capsulotomy was performed 4.5 +/- 4.3 months
      after surgery. The mean refractive shift after Nd:YAG capsulotomy was 1.9 +/- 1.9
      Dpt. CONCLUSIONS: Unexpected postoperative myopic correction was the main
      manifestation of capsular block syndrome in this series. Intraoperative use of
      miotics prohibiting optical control of complete viscoelastic removal may explain
      the high proportion of combined procedures. In the case of unexpected
      postoperative myopia the position of the intraocular lens within the bag should
      be checked and attention should be paid to possibly incompletely removed
      viscoelastic material.

PMID- 15162268
TI  - [Retrospective analysis of deep lamellar keratoplasties].
AB  - BACKGROUND: Purpose of this retrospective study was to analyse the outcome of
      deep lamellar keratoplasty. PATIENTS AND METHODS: The records of 9 patients with
      deep lamellar keratoplasty were reviewed. Age, sex, systemic diseases, indication
      for surgery, pre- and postoperative visual acuity and findings, visual acuity and
      findings at last follow-up and complications were noted. RESULTS: Nine eyes of 9
      patients have been operated with the "big bubble" technique described by Anwar.
      Indications for operation were keratoconus (4), keratoglobus (1), central corneal
      scar after keratitis (3) and after alkali burn (1). In 3 cases the intraoperative
      technique had to be changed to penetrating keratoplasty. The preoperative visual
      acuity was 0.2 to 0.3. All 9 patients showed a postoperative improvement of
      visual acuity: best corrected from 0.3 to 0.8. In one eye particles in the
      interface were found. At last follow-up all grafts were clear. There were no
      postoperative complications. CONCLUSIONS: The results demonstrate that deep
      lamellar keratoplasty is a technically difficult procedure, in 3 out of 9
      patients the operation method failed. The postoperative course after deep
      lamellar keratoplasty did not show any severe complications. The patients who had
      to be changed to penetrating keratoplasty were not disadvantaged in respect of
      the final result (visual acuity and findings). The postoperative visual acuities
      after deep lamellar keratoplasty and after penetrating keratoplasty were
      comparable. Despite the small number of patients and the relatively short
      observation period, we noticed that after deep lamellar keratoplasty the sutures
      could tendentially be removed earlier and thus the duration of topic steroids
      therapy was shorter compared to penetrating keratoplasty.

PMID- 15162271
TI  - Clinical outcomes and complications of intraocular lens exchange in patients with
      opacified hydrophilic acrylic lenses SC600-2.
AB  - BACKGROUND: The purpose of this study was to present the outcomes of intraocular
      lens exchange in patients with opacified hydrophilic acrylic intraocular lenses.
      PATIENTS AND METHODS: Fifteen patients, who underwent uncomplicated
      phacoemulsification and hydrophilic acrylic intraocular lens (model SC600-2)
      implantation with good visual recovery, were re-referred to our department 76 -
      188 weeks post-surgery due to progressive visual loss resulting from
      opacification of the implant. Intraocular lens exchange followed. The method of
      lens exchange is described. The effect on the best corrected visual acuity and on
      their refraction, the operative and postoperative complications are reported.
      RESULTS: All 15 patients underwent intraocular lens exchange. Twelve patients (80
      %) had improvement of their best corrected visual acuity, in two cases (13 %) the
      best corrected visual acuity did not change, and in one case (7 %) the best
      corrected visual acuity deteriorated, this being attributed to progression of her
      age-related macular degeneration. None of the patients developed zonular
      dehiscence; in one patient the exchange was complicated with posterior capsule
      rupture, and an anterior chamber intraocular lens was implanted. One patient
      required cutting of the haptics before removal of the opacified intraocular lens.
      The mean Snellen (decimal) visual acuity was 0.35 (range 0.1 to 0.6) before lens
      exchange and 0.49 (range 0.1 to 0.6) six weeks after; the difference was
      significant (P < 0.05). Excluding the patient with the deterioration of her age
      related macular degeneration, mean visual acuity of the remaining fourteen
      patients after the intraocular lens exchange was even better (0.56). CONCLUSION:
      Exchange of opacified hydrophilic acrylic intraocular lenses seems to be the only
      currently available effective treatment, leading to improvement of visual acuity.

PMID- 15162272
TI  - Phacoemulsification with intraocular lens implantation in patients with uveitis.
AB  - BACKGROUND: Cataract remains a challenge for ophthalmologists in uveitic eyes.
      The aim of this study is to report the clinical course of phacoemulsification
      with intraocular lens implantation in eyes suffering from uveitis. PATIENTS AND
      METHODS: Patients presenting a uveitis were prospectively followed from June 2001
      to June 2003. Ocular surgery was performed according to a standard protocol,
      autoimmune follow-up visits were focused on the early detection of complications
      of uveitis: increased ocular inflammation, synechiae, retraction of the rhexis,
      opacification of the posterior capsule or onset of cystoid macular edema.
      RESULTS: Thirty-two eyes of 24 patients suffering from uveitis were operated with
      cataract surgery between June 2001 and June 2003. The mean age at surgery was 56
      years (range 24 - 86 years). Mean preoperative visual acuity in uveitis patients
      presenting cataract was 0.3 +/- 0.3, and final visual acuity was 0.8 +/- 0.3.
      Three patients presented minor postoperative complications. One patient had a
      cystoid macular edema that appeared 5 months after surgery and one patient had a
      relapse of herpetic dendritic keratopathy despite topical antiviral therapy
      combined with steroid drops. The latter presented a slight increase of
      intraocular pressure (24 mm Hg). CONCLUSIONS: In patients with uveitis requiring
      cataract surgery, intraocular lens implantation is safe. Visual prognosis is
      better when pre- and postoperative inflammation is minimized. Macular scars or
      other retinal lesions are poor prognostic indicators.

PMID- 15162273
TI  - Comparing phacoemulsification and extracapsular cataract extraction in eyes with
      pseudoexfoliation syndrome, small pupil, and phacodonesis.
AB  - BACKGROUND: This study aims to compare the frequency of intraoperative and
      postoperative complications between the modern phacoemulsification technique and
      the extracapsular cataract extraction technique in patients with
      pseudoexfoliation syndrome. PATIENTS AND METHODS: A prospective randomized study
      comprised 94 eyes with cataract, pseudoexfoliation syndrome, small pupil and
      slight to moderate phacodonesis. These eyes were randomly assigned into two
      groups. In the first group all patients (47 eyes) were operated on using a
      standard phacoemulsification technique (iris hooks, anterior capsule staining and
      capsular tension ring after capsulorhexis), while in the second group all
      patients (47 eyes) underwent a classic extracapsular cataract extraction. The
      main outcome measures were the frequency of intraoperative zonular tears,
      capsular rupture, vitreous loss and corneal edema, as well as the best-corrected
      visual acuity. RESULTS: Intraoperative zonular separation was recorded in one eye
      (2.1 %) and in 15 eyes (31.9 %) for the first and second groups, respectively (P
      < 0.001). Posterior capsule rupture with or without zonular separation occurred
      in two eyes (4.2 %) of the first group and in eight eyes (17.0 %) of the second
      group (P < 0.05). Vitreous loss also had a higher rate in the second group (17.0
      % versus 4.2 %, P < 0.05). The postoperative difference in best-corrected visual
      acuity was also significant between the two groups, being higher in patients
      operated on using phacoemulsification technique (P < 0.001). CONCLUSIONS: In the
      difficult cases of cataract associated with pseudoexfoliation syndrome, small
      pupil and phacodonesis, the modern small-incision cataract surgery provides
      better results with a low rate of intraoperative and postoperative complications
      when compared with the extracapsular cataract extraction technique.

PMID- 15162274
TI  - [Filtering glaucoma surgery as outpatient procedure].
AB  - BACKGROUND: While cataract surgery is nowadays performed routinely as an
      outpatient procedure, performing filtering glaucoma surgery under these
      conditions remains questionable due to the more demanding perioperative
      management. PATIENTS AND METHODS: Outpatient filtering glaucoma surgery
      (trabeculectomy and combined phakoemulsification and trabeculectomy (phakotrab))
      is performed at the Ophthalmology Department of Kantonsspital Winterthur when
      requested by the patient. This paper provides a retrospective review of all
      outpatient filtering glaucoma procedures performed in the last three and a half
      years. RESULTS: Forty-six filtering procedures (21 trabeculectomies and 25
      phakotrabs) were performed in 45 eyes of 40 patients (50 - 84 years) as
      outpatient procedures. Mitomycin C was administered in 16/21 trabeculectomies and
      in 7/25 combined procedures. In the trabeculectomy group, intraocular pressure
      (IOP) was surgically lowered from 23.3 +/- 7.2 mm Hg (under 2.4 +/- 0.8 IOP
      lowering medications) to 12.7 +/- 3.5 mm Hg (20/21 patients without medication).
      In the combined group, IOP was lowered from 20.8 +/- 6.3 (under 2.0 +/- 0.7
      medications) to 13.7 +/- 2.7 mm Hg (only 5/25 patients still requiring IOP
      lowering medications). In the latter group, the best corrected visual acuity was
      below 20/40 only in 2 eyes due to advanced glaucomatous optic atrophy. One
      patient developed relative intraocular hypotony (IOP 6 mm Hg), one patient
      required needling + 5-fluorouracil injection and one patient required surgical
      revision of the trabeculectomy after 14 months. DISCUSSION: Adequate patient
      selection and refined surgical technique (tight wound closure and releasable
      sutures or argon laser suturolysis) allow performing filtering glaucoma surgery
      as an outpatient procedure. Extended post-operative care during the first 2
      months is the key for IOP-lowering success.

PMID- 15162275
TI  - Deep sclerectomy for the management of uncontrolled uveitic glaucoma: preliminary
      data.
AB  - BACKGROUND: If medical treatment fails in uveitic glaucoma a surgical approach
      should be considered. Classical trabeculectomy is known to have a less favourable
      outcome in uveitis. Our intention is to report the first series of uveitis
      patients with glaucoma resistant to medical therapy who were treated with deep
      sclerectomy (DS). PATIENTS AND METHODS: Fourteen eyes of 13 patients (mean age
      39.0 +/- 18.5 years; range 8 to 76 years) with chronic uveitis underwent non
      penetrating filtering surgery from 1995 to 2003. All patients had their uveitis
      controlled before and after surgery by immunomodulatory therapy. Non-penetrating
      filtering surgery consisted of DS with collagen implant (Staar(R)) in 4 eyes, DS
      with draining device (T-Flux Ioltech(R)) in 2 patients, DS without implant in 7
      patients and with viscocanalostomy in 1 patient. Nine eyes (65 %) received
      mitomycin C peri-operatively. RESULTS: Intra-ocular pressure (IOP) was reduced
      from a mean pre-operative value of 42.8 +/- 13.6 mmHg to a 1-year mean post
      operative value of 12.1 +/- 4.0 (71.7 % reduction). Eleven of the 14 eyes
      completed 12 months of follow-up, resulting in complete success in 5 (45.4 %) and
      in qualified success in 5 (45 %) and in failure in one patient (9.2 %), later
      controlled by a second operation. Anti-glaucomatous medication was reduced from a
      mean of 3.7 +/- 0.5 medications preoperatively to 1.2 +/- 0.8 medications (71.4 %
      reduction) at the 12 month follow-up. Nine of the 14 patients achieved a 24 month
      follow-up with a mean IOP of 14.1 +/- 3.8 mmHg and mean of anti-glaucomatous
      medications of 1.6. Four patients have been examined 4 years after the DS: mean
      IOP was 13.2 +/- 2.2 mmHg and mean medication 1.7 +/- 1.0. Post-operative
      complications included one case of lens opacity and 2 cases of hypotony lasting
      for five months and four weeks after the intervention respectively. CONCLUSION:
      Non-penetrating filtering surgery controlled the intra-ocular pressure in 90 % of
      eyes with uveitic glaucoma resistant to medical therapy at 12 months. Surgical
      complications were low which may explain the high success rate of the procedure,
      compared to classical penetrating surgery.

PMID- 15162276
TI  - Endoscopic laser coagulation of the ciliary processes in patients with severe
      chronic glaucoma.
AB  - BACKGROUND: To investigate the effect of endoscopic laser coagulation on the
      ciliary processes in order to control intraocular pressure (IOP) in patients with
      severe chronic glaucoma. PATIENTS AND METHODS: 6 eyes (5 pseudophakic, 1 phakic)
      of 5 patients (mean age 60 years, range 46 - 70) were treated. Glaucoma was
      related to previous detachment surgery (patients 1), panuveitis (patient 2), iris
      dystrophy (patient 3), or neovascularization (patient 4: central venous
      occlusion; patient 5: proliferative diabetic retinopathy). Preoperatively, all
      patients had not responded to intensive glaucomatous topical and systemic
      treatment (mean 4.2 drugs, range 3 - 5). Trabeculectomy has been unsuccessfully
      performed in patients 2 and 3. After pars plana vitrectomy, the ciliary processes
      were coagulated under endoscopic view over 180 - 270 degrees using endolaser
      (argon green with spots of 300 - 500 mW for 0.4 - 0.5 s). Patient 5 was treated
      in both eyes. RESULTS: The mean preoperative IOP was 39 mm Hg (range 32 - 47).
      The mean postoperative follow-up was 339 days (range 125 - 485). The
      postoperative IOP was over 1 year under 21 mm Hg in patient 1 with one topical
      drug, and in patients 2 and 3 without any further treatment. Patient 4 needed
      trabeculectomy and one topical drug to control IOP. The IOP was not controlled in
      patient 5 with the shortest follow-up despite additional topical treatment. No
      serious treatment-related complication was noted. CONCLUSIONS: Endoscopic laser
      coagulation allows a precise destruction of the ciliary processes, and permits a
      better control of IOP in certain cases of severe chronic glaucoma. Further
      investigations are necessary to better evaluate this therapy.

PMID- 15162277
TI  - Dynamic contour tonometry for post-LASIK intraocular pressure measurements.
AB  - BACKGROUND: Standard applanation tonometers are subject to systematic errors when
      applied to corneas with non-standard properties. Dynamic contour tonometry has
      been proposed as an alternative method for obtaining correct IOP data from such
      corneas. We have examined its applicability for patients who have undergone LASIK
      surgery. PATIENTS AND METHODS: 20 healthy individuals scheduled for bilateral
      myopic LASIK were selected. Pre- and postoperative examination (3 months)
      included applanation tonometry (Goldmann), contour tonometry, pachymetry,
      keratometry, and refraction. LASIK was performed with an MEL-70 Excimer Laser and
      a Hansatome Microkeratome. A tobramycin/dexamethasone preparation (Tobradex eye
      drops) was prescribed during one week after surgery. RESULTS: Applanation
      tonometry and contour tonometry furnished comparable IOP results prior to surgery
      (GAT: 15.1 +/- 2.2 mm Hg [mean +/- SD] DCT: 17.0 +/- 2.2 mm Hg), with corneal
      thickness ranging from 473 - 601 micro m (mean: 555 micro m). 3 months
      postoperatively, mean corneal thickness was reduced by - 85 micro m. Contour
      tonometer readings were not significantly different from preoperative results
      (16.0 +/- 2.4 mm Hg); whereas the Goldmann tonometer furnished significantly
      lower values at 11.8 +/- 1.3 mm Hg. CONCLUSIONS: Preoperative IOP measurements
      with the two types of tonometer were in good agreement. Post-operative results
      with the contour tonometer agree well with preoperative figures. However, the
      Goldmann tonometer furnishes values 3.3 mm Hg lower on average. This result is
      indicative of a significant measurement error of this device on post-LASIK eyes,
      which persists even 3 months postoperatively. The Dynamic contour tonometer
      appears to be suitable, reliable, and easy to use for IOP measurements after
      LASIK surgery.

PMID- 15162278
TI  - Differential inflammatory involvement in retina and choroid in birdshot
      chorioretinopathy.
AB  - BACKGROUND: Birdshot chorioretinopathy is characterised by dual unrelated
      inflammatory involvement of the retina and the choroid. Indocyanine green
      angiography made it possible to assess and follow choroidal disease with the same
      precision as retinal involvement was followed so far. The aim of this study was
      to analyse the severity, progression and response to therapy of both retinal
      involvement using fluorescein angiography and choroidal involvement using
      indocyanine green angiography. PATIENTS AND METHODS: Patients with birdshot
      retinochoroidopathy followed at La Source Eye Centre in Lausanne, Switzerland
      from January 1995 to December 2002 were subdivided into three subgroups according
      to the duration of evolution of the disease: untreated patients with no more than
      one year duration of the disease (group 1, n = 6); treated patients with disease
      duration of 1 - 7 years duration (group 2, n = 5) and patients with disease
      lasting for more than 7 years (group 3, n = 4). Fluorescein and indocyanine green
      angiographic signs (angiographic scores given by a masked observer) were analysed
      in the 3 groups and compared to the "cream-coloured" fundus lesions. RESULTS:
      Fifteen out of the 742 patients (2.0 %) seen at La Source Eye Centre during the
      time period considered presented BC and were included in the study. In the "early
      disease group" fluorescein and ICG angiography showed more severe choroidal than
      retinal involvement with respective scores of 3 +/- 0.79 (ICG) and 2 +/- 1.17
      (FA) while there were few depigmented fundus lesions to be seen (score 1 +/-
      0.27). The choroidal involvement responded well to systemic corticosteroids +/-
      immunosuppressive therapy (scores in groups 2 and 3 = 1.2 and 0.75), while
      retinal disease was stabilised at best (scores in groups 2 and 3 = 2.2. and 2.4)
      and depigmented fundus lesions increased (scores in groups 2 and 3 = 2.8 and 3).
      CONCLUSION: The evolution and response to therapy of retinal and choroidal
      disease in birdshot chorioretinopathy have a different course with choroidal
      disease responding well to therapy while retinal disease is more resistant,
      possibly explaining the slow deterioration of functional parameters despite
      therapy. The increase of "cream-coloured" fundus lesions despite good choroidal
      response to therapy could be explained by depigmentation left behind after
      resolution of choroidal stromal granulomas, a hypothesis recently confirmed by an
      autopsy case of birdshot chorioretinopathy.

PMID- 15162279
TI  - Increased endothelin-1 plasma level in young adults with retinal vascular
      occlusive diseases.
AB  - BACKGROUND: Vascular occlusive diseases are usually seen in the elderly but can
      occur even in younger patients without arteriosclerosis. We assume a vascular
      dysregulation as a underlying pathogenetic mechanism. PATIENTS AND METHODS: In a
      prospective study we analysed the clinical findings of six patients under 55
      years of age, three men with retinal vein occlusions and three women with branch
      retinal arterial obstructions. They were examined for signs of a vascular
      dysregulation and the endothelin-1 (ET-1) plasma level was measured. RESULTS: In
      all patients the ET-1 plasma level was markedly elevated. The mean value (3.72 +/
      0.8 pg/ml) was significantly increased compared to normal values for that age
      (1.52 +/- 0.24 pg/ml; p < 0.001). In all cases an increased tendency for vascular
      dysregulation could be demonstrated in nailfold capillaroscopy. Furthermore,
      frequent coldness of the extremities was mentioned by every patient and migraine
      was mentioned by four patients whereas neither changes of the vessels in carotis
      and ophthalmica region nor disturbances in the haemostasis and fibrinolysis could
      be found. CONCLUSIONS: All six patients with vascular occlusive diseases
      occurring before the age of 55 had a vascular dysregulation and increased ET-1
      plasma levels. A relationship between the vascular dysregulation and the vascular
      occlusive diseases is therefore likely.

PMID- 15162280
TI  - The value of white blood cell count in patients with swollen discs.
AB  - BACKGROUND: A broad differential diagnosis has to be considered in a patient with
      swollen discs. Myeloproliferative disorders such as leukemia and lymphoma can in
      rare cases cause infiltrative optic neuropathy. HISTORY AND SIGNS: Two patients
      initially presented with slowly progressive severe visual loss. History was
      unremarkable except for previously noted slightly elevated white blood cell count
      for which - according to their general physicians - no treatment or work-up was
      required. At presentation, bilateral disc swelling was present. Magnetic
      resonance imaging showed enhancement of the entire optic nerves sparing the
      chiasm. No other intracranial lesion was found. Cerebrospinal fluid contained no
      malignant cells. THERAPY AND OUTCOME: After bone marrow aspiration the diagnosis
      of non-Hodgkin's lymphoma and granulocytic leukemia, respectively, was made.
      Treatment resulted in visual recovery. CONCLUSION: Work-up in a patient with
      swollen discs should always include white blood cell count. If the result is
      abnormal further exploration should be pursued. Elevated white blood cell count
      may be the only hint of optic nerve infiltration caused by a myeloproliferative
      disorder and its treatment can result in remarkable recovery.

PMID- 15162281
TI  - Effect of visual stimulation on blood oxygenation in the optic nerve head of
      miniature pigs: a pilot study.
AB  - BACKGROUND: Visual stimulation is increasingly used to investigate the coupling
      between neuronal activity, blood flow and metabolism in the neural tissue of the
      ocular fundus. In an attempt to clarify whether the oxygen metabolism is involved
      in this coupling, we investigated the changes in the partial pressure of oxygen
      of venous blood (pO (2,blood)) in the optic nerve head of pigs in response to two
      different visual stimuli. MATERIALS AND METHODS: In 3 miniature pigs, the pO
      (2,blood) was measured in the optic disk rim using the technique of
      phosphorescence quenching by oxygen. This parameter was recorded every 8 seconds
      during a dark-to-light transition and during diffuse luminance flicker (field of
      30 degrees centered at the optic disk, temporal frequencies of 2 to 80 Hz).
      RESULTS: The venous pO (2,blood) level (mean +/- standard deviation) did not
      change between dark- and light-adapted conditions (26.2 +/- 5.3 and 26.0 +/- 6.2
      mm Hg, respectively), nor did we observe any transient change of pO (2,blood)
      during the light adaptation phase. On the other hand, the venous pO (2,blood)
      increased, on average, relative to its level during continuous light conditions
      (24.5 +/- 1.9 mm Hg) by at least 6 % for all flickering frequencies, with a
      maximum response of 14 % at 15 Hz. CONCLUSIONS: The phosphorescence quenching
      technique can reveal changes in venous pO (2,blood) induced by visual
      stimulation. Our results show that the pO (2,blood) in the optic nerve head of
      miniature pigs does not change with the light adaptation state of the retina, but
      increases during flicker stimulation with a band-pass type response. The
      previously reported increase of the ONH blood flow in response to flicker
      stimulation could lead to this increase of pO (2,blood).

PMID- 15162282
TI  - Effect of acetazolamide on the optic disc oxygenation in miniature pigs.
AB  - BACKGROUND: The purpose of our study was to evaluate the variations of the optic
      disc PO (2) during normoxia and hyperoxia (100 % O (2)), before and after
      intravenous administration of acetazolamide. MATERIAL AND METHODS: PO (2)
      measurements were obtained at intervascular areas of the optic disc in 11
      anaesthetized miniature pigs using oxygen-sensitive microelectrodes introduced
      through the vitreous cavity by a micromanipulator. PO (2) was measured
      continuously during 10 minutes under systemic normoxia and systemic hyperoxia.
      Oxygen measurements were repeated under these conditions after intravenous
      injection of acetazolamide (bolus of 500 mg) in 8 animals. RESULTS: In systemic
      hyperoxia, the optic disc PO (2) increased moderately (DeltaPO (2) = 4.7 +/- 2.5
      mmHg; p < 0.001; n = 11) in parallel with systemic PaO (2). Acetazolamide led to
      a slow and progressive increase in the optic disc PO (2) (DeltaPO (2) = 2.1 +/-
      1.7 mmHg; p > 0.1; n = 8 after 10 min, while DeltaPO (2) = 4.3 +/- 3.2 mmHg; p <
      0.05; n = 8 after 30 min), in parallel with a slow and progressive increase in
      systemic PaCO (2). The optic disc PO (2) increased much more significantly after
      injection of acetazolamide under systemic hyperoxia (DeltaPO (2) = 13.3 +/- 3.1
      mmHg; p < 0.001; n = 8). CONCLUSIONS: Systemic hyperoxia alone is not sufficient
      to increase substantially the optic disc PO (2) in miniature pigs due to a
      vasoconstrictor effect. Intravenous injection of acetazolamide can increase the
      optic disc PO (2) progressively, due to a vasodilatory effect of elevated
      systemic PaCO (2). The association of acetazolamide injection with systemic
      hyperoxia can further improve the oxygenation of the optic disc.

PMID- 15162283
TI  - Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization
      secondary to toxoplasmic chorioretinal scar.
AB  - BACKGROUND: To assess the effect of photodynamic therapy in the treatment of
      subfoveal choroidal neovascularization consecutive to a toxoplasmic chorioretinal
      scar. HISTORY AND SIGNS: Three patients with a previous history of toxoplasmic
      chorioretinal scar noticed a decrease in visual acuity and metamorphopsia. Fundus
      examination and fluorescein angiography revealed the presence of subfoveal
      choroidal neovascularization at the edge of the toxoplasmic chorioretinal scar.
      THERAPY AND OUTCOME: The first patient, aged 78, was treated by photodynamic
      therapy followed by three subsequent treatments of feeder vessel by laser
      photocoagulation. Visual acuity decreased during follow-up in the presence of
      recurrence of choroidal neovascularization and subretinal fibrosis. The second
      patient, a 20-year-old lady, was treated with three sessions of photodynamic
      therapy for a subfoveal choroidal neovascularization related to a toxoplasmic
      scar. Visual acuity was stabilized on the last follow-up visit at 0.3. The third
      patient, aged 53, received four treatments with photodynamic therapy at an
      interval of 3 - 4 months. choroidal neovascularization was stabilized and the
      last visual acuity was 0.2. CONCLUSIONS: This preliminary report suggests that
      photodynamic therapy with verteporfine may be an effective therapeutic modality
      for subfoveal choroidal neovascularization related to a toxoplasmic chorioretinal
      scar. Further assessment is needed in order to confirm this preliminary findings.

PMID- 15162285
TI  - [The value of multifocal ERG in diagnosis of discrete macular dystrophies].
AB  - BACKGROUND: Multifocal ERG is being extensively applied to numerous retinal
      disorders. It has gained particular clinical value in retinal disorders
      developing without morphological alterations. PATIENTS AND METHODS: We
      investigated a series of 4 patients, aged 10, 18, 29, and 49 years, respectively.
      When examined, they complained of photophobia and slowly progressive bilateral
      loss of vision, visual acuity ranging from 0.7 to 0.1. RESULTS: Ophthalmoscopic
      examination showed no or minimal alterations such as subtle granular changes in
      the fovea. Photopic-scotopic full-field ERG was normal. Multifocal ERG, in
      contrast, showed markedly reduced signal amplitudes within the central 10
      degrees. CONCLUSIONS: Based on the results of multifocal ERG, we were able in
      each case to consider with a high degree of probability the diagnosis of
      progressive foveal cone dystrophy. This is to emphasize the sensitivity of
      multifocal ERG in disorders affecting primarily the macula, without morphological
      changes, as cone (-rod) dystrophy, early Stargardt dystrophy, etc. The uttermost
      advantages of multifocal ERG are its innocuity, its applicability to children and
      the very early sensitivity to changes in retinal function.

PMID- 15162284
TI  - [Kinetics of indocyanine green (ICG) and clinical use for enhancement of
      transpupillary thermotherapy (TTT) in hypopigmented small choroidal melanomas].
AB  - BACKGROUND: To determine the efficacy of intravenous indocyanine green (ICG) as
      an adjuvant to TTT for hypopigmented choroidal melanomas. PATIENTS AND METHODS:
      ICG kinetics in melanoma tissue were evaluated by taking standardized ICG
      angiograms in 28 eyes with small choroidal melanomas. In a prospective non
      randomized analysis 12 eyes with hypopigmented choroidal melanomas (posterior to
      the equator with thickness </= 4.5 mm) were treated with the TTT standard
      protocol developed by an intravenous injection of 100 mg ICG in 10 ml aqueous
      solvent 2 minutes after starting TTT. These eyes were followed-up for at least 22
      months (mean 29). RESULTS: Pharmacokinetic analyses revealed the onset of
      fluorescence after 42 seconds (mean) in pigmented versus 22 seconds in amelanotic
      tumors. Persistence of maximum fluorescence was found for 20 minutes (mean)
      irrespective of the grade of pigmentation. Six eyes revealed tumor regression
      within 2 - 4 months after one treatment session. Three eyes flattened after two
      sessions within 6 - 8 months. Three eyes were judged as failures (two required
      ruthenium-106 radiotherapy because of insufficient regression after two sessions
      of TTT and one eye was enucleated because of regrowth after radiotherapy and
      TTT). Visual acuity was unchanged or improved in 7 eyes. Ocular side effects were
      epiretinal gliosis (2), macular edema (1) and temporary retrobulbar pain (3).
      CONCLUSIONS: TTT with adjuvant ICG was successful in 9 out of 12 hypopigmented
      tumors. Further research with a larger sample of patients in a prospective and
      randomized analysis and longer follow-up are mandatory to determine the role of
      ICG in TTT.

PMID- 15162286
TI  - Visual vertigo: an observational case series of eleven patients.
AB  - BACKGROUND: Dizziness is a common symptom which is frequently due to either
      peripheral or central vestibular dysfunction. However, some patients may lack
      typical signs suggesting a vestibular or cerebellar lesion and they mostly
      complain of vertigo or posture imbalance induced by visual stimulation. The
      symptoms immediately improve either on cessation of the visual input or upon
      closure of the eyes. Such a presentation is typical of visual vertigo. PATIENTS
      AND METHODS: From 1993 to 2003, 242 patients were examined for either "vertigo"
      or "dizziness". The diagnosis of visual vertigo was based on both history and
      clinical examination and was present in 11 patients. RESULTS: Visual vertigo was
      diagnosed in 11/242 patients (4.5 %). Age range was 31 - 77 years (mean 47 years)
      with a sex ratio of 8 females for 3 males. Neuro-ophthalmological examination was
      normal in all cases. CONCLUSIONS: Visual vertigo is not a rare condition but the
      disease is underdiagnosed. The symptoms result from a mismatch between
      vestibular, proprioceptive and visual inputs. Neuro-ophthalmological,
      neurological and neuro-otological examination are often normal or not relevant
      and the diagnosis is largely based on history. It is important to recognize this
      entity because the symptoms might improve if the patients are treated with psycho
      motor rehabilitation.

PMID- 15162287
TI  - [Does amblyopia therapy make sense in eyes with severe organic defects?].
AB  - BACKGROUND: In eyes with severe organic defects the question arises if amblyopia
      therapy makes sense. PATIENTS AND METHODS: Three children are presented in whom
      despite severe organic eye diseases amblyopia therapy was tried. The first child
      had a unilateral large macular scar secondary to retinoblastoma treatment, the
      second a unilateral severe optic nerve atrophy secondary to an orbital
      hemangioma, and the third a unilateral large optic nerve coloboma. RESULTS: In
      the first case a reading visual acuity of 0.9 was achieved by occlusion therapy
      and in the second a reading visual acuity of 0.5. In the third case occlusion
      lead to alternation of the divergent strabismus (child too strongly retarded for
      reliable visual acuity measurements). CONCLUSIONS: During the sensitive phase,
      amblyopia therapy is also indicated in eyes with severe organic defects since
      good visual acuities can be achieved.

PMID- 15162288
TI  - Role of the stimulus size in the generation of optokinetic nystagmus in normals
      and in patients with retinitis pigmentosa.
AB  - BACKGROUND: To find out the smallest stimulus size still able to elicit
      optokinetic nystagmus (OKN). To discuss the differences in the generation of OKN
      between normals and patients with tunnel vision. METHODS AND PATIENTS: OKN was
      elicited monocularly with black and white stripes of 2 degrees moving on a screen
      temporally-to-nasally or nasally-to-temporally at velocities of 15, 30, 45, and
      60 degrees /s. In healthy subjects (n = 10) the size of the stimulus was
      gradually increased from minimal 8 degrees x 0.5 degrees to maximal 48 degrees x
      10 degrees. OKN was elicited in retinitis pigmentosa (RP) patients (n = 2) with
      visual field reduced to the central 10 degrees. OKN gain was measured using
      infrared oculography. OKN response was considered as normal if it was within 2
      standard deviations of the mean OKN of age-matched control groups (n = 29).
      RESULTS: In healthy subjects the size of the stimulus necessary to elicit normal
      OKN gain was smaller at low velocity of 15 degrees /s (16 degrees x 1 degrees )
      than at higher velocities of 30, 45, and 60 degrees /s (16 degrees - 24 degrees x
      3 degrees ). Normal OKN gain was measured in the RP patients only at the low
      velocity of 15 degrees /s. CONCLUSIONS: Small stimuli are sufficient in normals
      to elicit good OKN answers. Therefore, poor OKN gain in RP patients may not be
      explained by their tunnel vision only. We postulate that in these patients the
      reduction of gain is due to a multifactorial decrease of their visual perception
      related to disorders of the visual field, the visual acuity, and the contrast
      sensitivity.

PMID- 15162289
TI  - Free autologous buccal mucosal graft transplantation to treat ocular
      complications after toxic epidermal necrolysis: case report.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) can lead to ocular surface scarring
      associated with pain, dry eye symptoms, and decreased visual acuity that often
      are difficult to treat. HISTORY AND SIGNS: A 34-year-old woman was referred to
      our department two-years after TEN induced by lamotrigin (lamictal(R)). She was
      complaining of severe visual acuity loss, pain, and dry eye symptoms. Visual
      acuity was reduced to light perception in the right eye (RE) and to 0.2 in left
      eye (LE). Basal Schirmer test was 2 mm in RE and 3 mm in LE. With or without
      therapeutic contact lenses, the patient was experiencing severe discomfort
      requiring tear supplementation up to 50 - 80 times/day in both eyes. THERAPY AND
      OUTCOME: A free autologous mucosal graft (3.5 x 2.0 cm) was transplanted from the
      lower lip into the upper RE fornix. Six months after surgery, with therapeutic
      contact lenses, the need for tear supplementation was markedly reduced to 3 - 4
      times/day in RE while it remained unchanged in LE. In RE, slit-lamp examination
      revealed decreases in the corneal stromal edema and in the diameter of neo
      vessels associated with an improvement of visual acuity (counting fingers at 30
      cm). Basal Schirmer test values were unchanged. It has to be mentioned that the
      improvement observed after surgery was markedly dependent on wearing a
      therapeutic contact lens. CONCLUSIONS: Free autologous buccal graft
      transplantation (with its presumably accessory salivary glands) in association
      with the use of a therapeutic contact lens can be an efficient approach to treat
      ocular complication following drug-induced TEN (Lyell's syndrome).

PMID- 15162290
TI  - Follicular conjunctivitis caused by a mantle cell lymphoma.
AB  - BACKGROUND: Lymphoma of the conjunctiva as part of a systemic disease is rare.
      The follicular appearance of the lymphocyte hyperplasia may mimic the clinical
      picture of infectious or allergic conjunctivitis. We report on a case of marked
      chronic follicular conjunctivitis, finally diagnosed as mantle cell lymphoma.
      HISTORY AND SIGNS: A 52-year old male with a history of epiphora for one year,
      presented with follicular conjunctivitis in both eyes, a nodal mass in the upper
      right eyelid and nuchal lymphadenopathy. No infectious or allergic aetiology
      could be found. Conjunctival biopsy revealed a mantle cell lymphoma. Magnetic
      resonance tomography showed a bilateral spread into the orbital cavity. Other
      sites of involvement were the epipharynx and the cervical, axillary and
      paratracheal lymph nodes. THERAPY AND OUTCOME: Chemotherapy with hyper-CVAD
      (cyclophosphamide, vincristine, doxorubicine, dexamethasone) was initiated. After
      4 of 6 cycles, all clinical tumour manifestations had disappeared completely.
      CONCLUSIONS: Conjunctival lymphoma may clinically resemble follicular
      conjunctivitis. Conjunctival biopsy may lead to early diagnosis and initiation of
      therapy.

PMID- 15162293
TI  - Arachnoid cyst of the optic nerve: a case report.
AB  - BACKGROUND: To report a case of an arachnoid cyst of the optic nerve with
      homonymous optic atrophy. HISTORY AND SIGNS: A 17-year-old female patient
      presented with severe visual loss, limited to light perception, of the left eye.
      She underwent complete ophthalmologic examination, color fundus photography and
      electrophysiological study. Magnetic resonance imaging (MRI) revealed the
      presence of a fusiform structure involving the left optic nerve from the orbital
      apex to the posterior surface of the globe. The clinical and radiographic
      features are consistent with an arachnoid cyst of the optic nerve. THERAPY AND
      OUTCOME: The patient refused to be treated. Two years later, the VA remained
      unchanged. CONCLUSIONS: The arachnoid cyst of the optic nerve is a rare entity.
      Its differential diagnosis from the primary optic nerve glioma is difficult and
      important to be made in order to be treated properly.

PMID- 15162292
TI  - Selective and sequential therapy of oculomotor and palpebral sequelae resulting
      from biopsy of dorsal midbrain sarcoidosis.
AB  - BACKGROUND: Biopsy of a dorsal mesencephalon lesion often leads to neuro
      ophthalmological complications, namely dorsal mesencephalic syndrome, skew
      deviation, IV (th) palsy, or Horner's syndrome. HISTORY AND SIGNS: A 26-year-old
      man underwent a biopsy of the quadrigeminal plate for a lesion which revealed to
      be neurosarcoidosis. Post-operative complications included a left homonymous
      hemianopia, a left III (rd) nucleus palsy, a bilateral IV (th) palsy and a
      bilateral internuclear ophthalmoplegia. Palpebral fissures were narrowed to 2 mm
      on both sides. In primary gaze there was 24 degrees of exotropia, 17 degrees of
      right hypertropia and 30 degrees of exyclorotation. THERAPY AND OUTCOME: After 24
      months of stable evolution, three oculomotor surgical procedures were performed
      including: surgery on both horizontal muscles of the left eye; shortening of both
      superior oblique muscles; resection of the right lateral rectus muscle, and
      posterior fixation of an inferior rectus muscle. Bilateral brow suspension on the
      frontal muscle of both superior eyelids was then performed. Evolution was
      favorable with a binocular single field of vision measuring 17 degrees
      horizontally and 20 degrees vertically centered on the primary gaze. Palpebral
      fissures measured 7 to 8 mm in primary gaze. CONCLUSIONS: The neuro
      ophthalmological sequelae which followed the biopsy of a neurosarcoidosis lesion
      of the quadrigeminal plate were so severe that this patient was completely
      handicapped. A four-step surgery correcting the horizontal, torsional, vertical
      components, then the bilateral ptosis allowed the patient to recover both a
      satisfying function and esthetical aspect.

PMID- 15162291
TI  - [Primary intraocular lymphoma with unusual clinical presentation and poor
      outcome].
AB  - BACKGROUND: Primary intraocular lymphoma is a distinct subset of primary non
      Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of
      the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than
      1 % of all intraocular tumors. HISTORY AND SIGNS: A 70-year-old man was
      hospitalized in June 2002 because of acute loss of vision on his left eye. A
      severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal
      lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy
      was performed. An intraocular malignant B-cell lymphoma was determined by
      immunohistochemistry. General screening revealed no further manifestations of the
      lymphoma. THERAPY AND OUTCOME: The patient initially refused any therapy until a
      painful secondary neovascular glaucoma with complete loss of visual function
      developed, thus prompting us to perform an enucleation. The following
      immunohistochemical examination confirmed the initial diagnosis. A chemotherapy
      with high-dose methotrexate and leucovorin rescue was initiated. CONCLUSIONS:
      Primary intraocular lymphoma can present as diffuse uveitis refractory to
      corticosteroids. Diagnosis can be difficult and is often delayed.

PMID- 15162294
TI  - [Traumatic lesion of the optic nerve head by flying fish: a case report].
AB  - BACKGROUND: Traumatic lesion to the optic nerve often leads to severe and
      persistent functional loss. HISTORY AND SIGNS: A male patient was transferred to
      our hospital from the University Eye Clinic of Guadeloupe 5 days after ocular
      injury caused by a flying fish. Visual function was light perception. The
      anterior part of the eye and retina were unremarkable. A computer tomography
      disclosed a fracture of the sphenoid sinus, with a little bone fragment (DD:
      foreign body) located close to the optic nerve. THERAPY AND OUTCOME: Therapy had
      been started with Aminopenicillin combined with clavulan acid (Augmentin) i. v.,
      500 ml methylprednisolone (Solumedrol) i. v., lysine-acetyl salicylate (Aspegic)
      and topical application of dexamethasone combined with neomycin/polymyxin B
      (Maxitrol). We continued this therapy and intensified it by adding nimodipine
      (Nimotop) 30 1-1-1 and acetazolamide retard (Diamox sustet) 1-0-1. Unfortunately
      visual function did not recover under therapy. CONCLUSIONS: Traumatic lesions of
      the optic nerve head, especially when due to axial or tangential forces, can lead
      to severe and irreversible functional loss. Severe traumatic lesions, even bone
      fractures induced by flying fish are not a seldom encounter in the Caribbean Sea.

PMID- 15162295
TI  - Intraosseous meningioma: a rare cause of chronic optic neuropathy and
      exophthalmos.
AB  - BACKGROUND: The association of optic neuropathy, proptosis and chorioretinal
      folds is highly suggestive of an orbitopathy. Usual etiologies include an
      inflammatory orbitopathy, optic nerve sheath meningioma, sphenoid wing
      meningioma, exterioration of a sinus disorder, or an orbital tumor be it primary
      or secondary. HISTORY AND SIGNS: A 40-year-old man treated for systemic
      hypertension complained of decreased vision and floaters in his right eye.
      Initial examination revealed decreased visual acuity to 20/50 of the right eye
      with a slight dyschromatopsia, but a lack of afferent pupillary defect and normal
      visual fields. Fundus examination showed the presence of a slightly swollen right
      optic disc and chorioretinal folds. A diagnosis of presumed anterior ischemic
      optic neuropathy was made. Symptoms persisted and, five months later, right
      proptosis was noted. Magnetic resonance imaging revealed a diffuse thickening of
      the parieto-temporal bone and the greater wing of the sphenoid bone on the right
      side. Radiological differential diagnosis included fibrous dysplasia and
      metastasis. THERAPY AND OUTCOME: Bone biopsy revealed a grade I intraosseous
      meningioma. Conservative management was chosen because the lesion was too
      extensive to be resected and radiotherapy is usually not efficient on grade I
      meningiomas. CONCLUSIONS: Intraosseous meningiomas are benign tumors which are
      due to meningeal cells entrapment during vaginal delivery. It is a rare tumor of
      slow progression. Therapy usually consists of resection and cranioplasty and/or
      radiotherapy. In the present case, decompression of the optic canal remains
      feasible in case of further visual loss.

PMID- 15162297
TI  - Posterior ischemic optic neuropathy: case report of a rare complication after
      general surgery.
AB  - BACKGROUND: Posterior ischemic optic neuropathy (PION) is a rare cause of
      bilateral severe and bilateral visual loss. Three mechanisms for posterior
      ischemic optic neuropathy are recognized: arteritic, non-arteritic, and peri- or
      postoperative. We report a case of bilateral postoperative posterior ischemic
      optic neuropathy. HISTORY AND SIGNS: A previously healthy 51-year-old man
      complained of the sudden onset of visual loss and unformed visual hallucinations
      in both eyes, 24 hours after an uneventful lumbar spine surgery. Duration of
      surgery was 12 hours with 2.5 liters of blood loss. At the time of visual loss,
      anemia was 74 g/L. Ophthalmic examination revealed decreased visual acuity to
      count fingers and normal optic disc without swelling or hemorrhages in both eyes.
      THERAPY AND OUTCOME: Despite blood transfusion 2 days after visual loss,
      evolution was stable. One month later, visual acuity was 0.15 RE and 0.2 LE with
      severe dyschromatopsia. Pupils reacted sluggishly to light but briskly to
      convergence. Optic discs were diffusely pale. DISCUSSION: Peri- and postoperative
      posterior ischemic optic neuropathy is a rare but devastating complication of
      surgery performed at distance from the visual pathways and its vascularization.
      Risk factors include: spine surgery, peri-operative hypotension, anemia, facial
      edema. Early recognition of posterior ischemic optic neuropathy and rapid
      correction of hypotension and/or anemia might improve outcome of posterior
      ischemic optic neuropathy, which usually is poor.

PMID- 15162296
TI  - Multiple intraorbital neurofibromas: a rare cause of proptosis.
AB  - BACKGROUND: Orbital neurofibromas are rare, accounting for 0.5 to 2.4 % of all
      orbital tumors. Generally, they manifest as slowly progressive proptosis, in a
      young adult or middle-aged person, and are usually solitary lesions. Sometimes,
      they can be associated with type 1 neurofibromatosis. We present a case of
      proptosis related to multiple intraorbital neurofibromas in an 82-year-old woman
      without type 1 neurofibromatosis. HISTORY AND SIGNS: An 82-year-old woman was
      referred for slowly progressive left proptosis associated with an ocular burning
      sensation. Neuro-ophthalmic examination revealed 9.5 mm of left exophthalmos,
      signs of minimal left optic neuropathy but normal extraocular movements. Magnetic
      resonance imaging revealed the presence of 4 intraorbital lesions. THERAPY AND
      OUTCOME: The two most anterior tumors were removed. Pathological studies showed
      these tumors to be neurofibromas. Post-operative evolution was favorable with
      reduction of left proptosis to 7 mm and disappearance of the burning sensation of
      the left eye. No other signs of neurofibromatosis were found. CONCLUSIONS:
      Multiple circumscribed intraorbital tumors are rare. Slowly progressive proptosis
      with radiological imaging of multiple round lesions should evoke the diagnosis of
      orbital neurofibromas, even in patients outside the typical age range or without
      neurofibromatosis.

PMID- 15162298
TI  - Retinal vasculitis and cystoid macular edema after body tattooing: a case report.
AB  - BACKGROUND: To report a case of retinal vasculitis occurring after the placement
      of permanent tattoos. HISTORY AND SIGNS: A 21-year-old male was referred to our
      department with impairment of visual acuity. Permanent tattoos covered the head,
      body, arms and legs. The patient was examined with ophthalmoscopy, fluorescein
      angiography, indocyanine green angiography and optical coherence tomography.
      Systemic medical and laboratory work-up were performed in order to exclude an
      infectious agent or an inflammatory disease. He had no history of intravenous
      drug abuse. THERAPY AND OUTCOME: Our patient presented severe posterior uveitis
      associated with retinal vasculitis and cystoid macular edema. Laboratory tests
      ruled out all diseases causing vasculitis. HIV and B, C hepatitis tests were
      negative. Cystoid macular edema and vasculitis were resolved after
      immunosuppressive therapy. CONCLUSIONS: This is the first description of a
      retinal vasculitis associated with cystoid macular edema in a completely healthy
      individual after the placement of permanent tattoos. A phagocytosis of tattoo
      pigments leading to their lysis is described in the literature as a mechanism
      causing vasculitis.

PMID- 15162299
TI  - Juvenile neuronal ceroid lipofuscinosis (Batten disease) CLN3 mutation (Chrom
      16p11.2) with different phenotypes in a sibling pair and low intensity in vivo
      autofluorescence.
AB  - BACKGROUND: The neuronal ceroid lipofuscinoses (Batten disease) are a
      heterogeneous group of autosomal recessively inherited disorders causing
      progressive neurological failure, mental deterioration, seizures and visual loss
      secondary to retinal dystrophy. The juvenile type is of special interest to the
      ophthalmologist as visual loss is the earliest symptom of the disorder. HISTORY
      AND SIGNS: We present two siblings with severe retinal dystrophy due to juvenile
      Batten disease. Sibling A (age 10) presented with visual loss, photophobia and
      night blindness, starting at age 4. His vision was perception of light by the age
      of 10.5 years. Fundus examination revealed severe pigmentary retinopathy. Sibling
      B (age 7) presented with night vision difficulties. Fundus examination revealed a
      bull's eye maculopathy with minimal peripheral atrophic changes. In vivo
      autofluorescence level was found to be very low. Electroretinography (ERG) showed
      generalized retinal dysfunction involving both cone and rod systems, with an
      electronegative maximal response. In both siblings vacuolated lymphocytes were
      found on a peripheral blood film and on molecular genetic testing both were
      homozygous for the commonly reported 1.02-kb deletion of the CLN3 gene. THERAPY
      AND OUTCOME: Although there is no effective treatment, the early diagnosis
      allowed accurate genetic and social counseling. CONCLUSIONS: Juvenile Batten
      disease should be considered in children with a retinal dystrophy, especially
      where there is a bull's eye maculopathy and an abnormal full field ERG. The novel
      finding of very low in vivo autofluorescence is consistent with histopathological
      studies and may be secondary to photoreceptor cell loss.

PMID- 15162300
TI  - Normalisation of ocular pulse amplitude after embolisation of dural cavernous
      sinus arteriovenous fistula.
AB  - BACKGROUND: The difference in the ocular pulse amplitude between an individual's
      eyes may reflect abnormalities of the cerebrovascular circulation and has been
      shown to be helpful in assessing patients with cavernous sinus arteriovenous
      fistulas. HISTORY AND SIGNS: A 71-year-old woman presented with episcleral
      injection, proptosis, bruit and retro-orbital pain on the left side. Ocular pulse
      amplitude as measured by dynamic contour tonometry was 4.38 +/- 1.23 mm Hg in the
      right and 9.57 +/- 2.71 mm Hg in the left eye. Angiography revealed the
      haemodynamics of a dural left cavernous sinus arteriovenous fistula. THERAPY AND
      OUTCOME: Successful occlusion of the fistula was performed by transvenous
      embolisation. After embolisation, ocular pulse amplitude was 2.84 +/- 0.60 mm Hg
      in the right and 1.88 +/- 0.29 mm Hg in the left eye. CONCLUSION: In this case of
      a dural arteriovenous fistula the ocular pulse amplitude as measured by dynamic
      contour tonometry parallels closely both clinical findings and neuroimaging.

PMID- 15162301
TI  - [Self-mutilation with crystalline lens dislocation in Gilles de la Tourette
      disease treated with retropupillary "iris claw" lens].
AB  - BACKGROUND: Gilles de la Tourette syndrome is a neurological disorder
      characterized by motor and vocal tics. Extreme forms of this disease manifest
      themselves with self-mutilating behavior and foul language. HISTORY AND SIGNS: A
      59-year-old man, treated for Gilles de la Tourette syndrome, presented with
      visual loss after an attack during which he punched his right eye with his fist.
      On examination visual acuity was decreased to finger counting but could be
      improved to 1.0 with an S + 13D lens. There was vitreous prolaps into the
      anterior chamber and pigment was noted in the vitreous cavity. The complete
      dislocated lens could be seen ophthalmoscopically in the inferior fundus of the
      eye. THERAPY AND OUTCOME: The patient was treated with vitrectomy and
      phacoemulsification through the pars plana. An additional encircling band was
      placed due to peripheral retinal tears in the inferior quadrants. Visual
      rehabilitation was achieved with a secondary implant of a retropupillary iris
      claw lens nine months later. DISCUSSION: Self-inflicted injuries are common in
      Gilles de la Tourette syndrome. Ocular lesions described in the literature
      comprise isolated cases of orbital hemorrhage, retinal detachment and permanent
      severe visual loss. Lens luxation has not been described before, and is probably
      due to weakened zonulae induced by repeated trauma. Treatment with a
      retropupillary iris-claw lens is the preferred therapy as it reduces the risk of
      endothelial touch during repeated trauma on the eye.

PMID- 15162302
TI  - [Fundus quiz 2003].
AB  - 6 cases with pathognomonic fundus pathologies are presented and discussed using
      multiple-choice questions.

PMID- 15162305
TI  - An introduction to congenital hand anomalies.
AB  - The intention of this introduction is to provide a platform from which ensuing
      articles may deal with the details of management of specific entities. A basic
      knowledge of the process of limb development and an appreciation of our current
      knowledge of the causations of abnormal limb development are necessary to assist
      the surgeon in explanation as to how and why the child has the limb anomaly.
      Undoubtedly it is from this knowledge that prevention and improved management
      will evolve in the future. Some words about classification are appropriate. This
      is always a contentious issue, as classification cannot currently be precisely
      related to causation but is necessary such that those working in the field can
      speak in one language and understand each other. Finally, I will outline a
      philosophy on which to base both indications for, and timing of surgical
      intervention.

PMID- 15162306
TI  - Genetics of congenital hand anomalies.
AB  - Congenital limb malformations exhibit a wide spectrum of phenotypic
      manifestations and may occur as an isolated malformation and as part of a
      syndrome. They are individually rare, but due to their overall frequency and
      severity they are of clinical relevance. In recent years, increasing knowledge of
      the molecular basis of embryonic development has significantly enhanced our
      understanding of congenital limb malformations. In addition, genetic studies have
      revealed the molecular basis of an increasing number of conditions with primary
      or secondary limb involvement. The molecular findings have led to a regrouping of
      malformations in genetic terms. However, the establishment of precise genotype
      phenotype correlations for limb malformations is difficult due to the high degree
      of phenotypic variability. We present an overview of congenital limb
      malformations based on an anatomic and genetic concept reflecting recent
      molecular and developmental insights.

PMID- 15162307
TI  - Embryology of the upper limb: the molecular orchestration of morphogenesis.
AB  - Accumulating data on the molecular interactions that occur during limb
      development have greatly enhanced our understanding of the process of limb
      morphogenesis. In this chapter, the key morphologic events are described, the
      broad categories of molecules involved are defined, the known molecular cascades
      and specific pathways that orchestrate limb development are reviewed. In
      addition, cascades disrupted by known genetic mutations associated with limb
      malformations are identified.

PMID- 15162308
TI  - Teratogenic mechanisms of longitudinal deficiency and cleft hand.
AB  - In order to better understand the teratogenic mechanisms of congenital defects of
      the digits, we analyzed clinical cases and induced similar types of congenital
      hand anomalies in rat fetuses by oral administration of busulfan. In clinical
      cases, radial and ulnar deficiencies had common characteristic features. We
      induced radial and ulnar deficiencies in rat fetuses with the same drug. Radial
      and ulnar deficiencies induced in rats have similar clinical manifestations and
      these anomalies might be caused by the same teratogenic mechanism. Then, the
      formation of the digital rays was examined histologically. The results of
      histological examination suggested that these deficiencies were not caused by
      localized damage of the limb bud. They also suggested that the cause of missing
      digits in longitudinal deficiency is closely related to a deficit of mesenchymal
      cells in the limb bud. Cleft hand is considered to be one of the types of
      longitudinal deficiency. However, several investigators have suggested that the
      abnormal induction of finger rays in the process of formation of fingers induced
      central polydactyly, osseous syndactyly and also cleft hand. X-rays of the
      clinical cases and skeletal changes of the anomalies induced in rats appear to
      demonstrate that cleft hand formation proceeds from osseous syndactyly and
      central polydactyly. The results of our experimental study show that the critical
      periods of central polydactyly, osseous syndactyly and cleft hand are the same.
      They also suggest that central polydactyly, syndactyly and cleft hand might be
      induced when the same teratogenic factor acts on embryos at the same
      developmental stage in the human being. Because they have a similar causation,
      cleft hand, syndactyly and central polydactyly should be classified into the same
      entity, that is, abnormal induction of digital rays. Based on these clinical and
      experimental studies, we modified the Swanson classification. In our modified
      classification, typical cleft hand, syndactyly and polydactyly are included in
      the same category of abnormal induction of digital rays as the fourth new
      category.

PMID- 15162309
TI  - The windblown hand - diagnosis, clinical picture and pathogenesis.
AB  - The syndrome of the windblown hand deformity is a complex constellation of
      malformations affecting not only the head and the feet but also the hands in a
      quite distinct manner. In the hand, it involves congenital bilateral flexion
      contracture with ulnar deviation of the metacarpophalangeal joints. The thumb is
      characteristically adducted (reaching the palm; "thumb-in-palm deformity") with
      flexion of the MP joint and hyperextension of the IP joint. The etiology is
      basically unknown. We present two theories based on knowledge derived from the
      disciplines of evolution biology and embryology. We believe that the atavistic
      appearance of phylogenetically primitive muscle groups in conjunction with an
      impaired rotation of the extremities during embryological development account for
      this malformation syndrome.

PMID- 15162310
TI  - Congenital duplication of the thumb.
AB  - Duplication or polydactyly of the thumb is among the most common congenital
      deformities that involve the hand. The purpose of this presentation is to review
      the Mayo Clinic experience with thumb duplication and to present preferred
      operative procedures to achieve the best clinical outcome and esthetic appearance
      for the hand. We propose that a combination or "best of parts", utilizing the
      components of both duplicates with retention of the ulnar duplicate as the base
      for reconstruction will provide the most functional clinical result. A clinical
      grading system and analysis of results from our personal experience during two
      different time frames provides the scientific support for our conclusions that
      combination procedures are preferred to simple excisions or to central joining of
      parts as in the Bilhaut-Cloquet procedure.

PMID- 15162311
TI  - Thumb duplication - simple surgery for a common problem?
AB  - Polydactyly is one of the most common congenital anomalies of the hand, and thumb
      duplication the most common manifestation of polydactyly. Despite this, the
      results of surgical treatment for thumb duplication are frequently disappointing,
      and deformities secondary to improperly executed reduction procedures often make
      further corrective surgery necessary. Examples of thumb duplication, their
      characteristic abnormal anatomy, and the complexity of surgical reduction
      procedures are illustrated.

PMID- 15162312
TI  - The "Bilhaut-Cloquet" technique for treatment of thumb duplication.
AB  - The presentation of thumb duplication is variable depending on the level of
      bifurcation, the relative sizes of the two thumbs and their possible symmetry
      along a longitudinal axis. Resection of the supernumerary thumb often leads to
      disappointing results when both thumbs are hypoplastic. The principle of the
      "Bilhaut-Cloquet" procedure involves central resection of the duplication
      followed by fusion of the remaining lateral portions, in order to obtain a thumb
      of satisfactory volume. Thirteen children with unilateral thumb duplication were
      treated using the "Bilhaut-Cloquet" procedure. Nine cases involved duplication of
      the distal phalanx (Wassel type II). Five of these duplications were symmetrical
      and four were asymmetrical with an associated proximal delta phalanx. In these
      cases, a corrective osteotomy of the delta phalanx was performed at the same
      time. Four cases involved symmetrical duplications of both proximal and distal
      phalanges (Wassel type IV). The mean age at time of surgery was 11.5 months.
      Patients were reviewed with a mean follow-up of four years. The aesthetic aspect
      of the nail was judged as good in 12 cases. In one case, the aesthetic aspect of
      the nail was judged as fair due to a prominent longitudinal ridge. Bony fusion
      was obtained in all cases but one. The alignment was corrected in all cases but
      four, involving asymmetrical duplications. Joint mobility was limited in all
      patients. The "Bilhaut-Cloquet" technique leads to a satisfactory volume of the
      thumb in selected cases. Good correction of preoperative angular deformity is
      obtained in symmetrical cases. A precise technique of bone and nail approximation
      yields good functional and aesthetic results. The "Bilhaut-Cloquet" technique is
      indicated in balanced and symmetrical duplications, when the two thumbs are
      severely hypoplastic. It can be used either in the distal or proximal phalangeal
      types of thumb duplication.

PMID- 15162313
TI  - Pollicization in congenital differences.
AB  - Pollicization of the index finger is a well established procedure for some cases
      of thumb hypoplasia. We reviewed our experience of 27 "normal" index-finger
      pollicizations with a mean follow-up of seven years, excluding those cases with
      more extensive radial hypoplasia and abnormal fingers. Even in such an "ideal"
      situation, strength was deceptive and the frequently slender aspect of the new
      thumb with quite extensive dorsal scar formation and the "cleft" appearance of
      the first web disappointing. In a prospective series of 32 cases, we tried to
      improve both the function and appearance of the thumb by modifying the classical
      incision as well as the transferred muscles and tendons.

PMID- 15162316
TI  - Kirner's deformity treated by distal detachment of the flexor digitorum profundus
      tendon.
AB  - Kirner's deformity may be due to a very distal insertion of the flexor digitorum
      profundus tendon along the palmar surface of the distal phalanx of the small
      finger. Distal detachment of the flexor digitorum profundus tendon has already
      led to encouraging results. Intraoperative findings, surgical technique and
      results are shown.

PMID- 15162315
TI  - The treatment of crossbones of the hand.
AB  - Over a thirty-year period at Loma Linda University, we have seen eight patients
      with nine crossbones of the hand. These patients fall into the group of central
      deficiency with a cleft hand and central polydactyly. As will be noted in the
      paper, these two conditions may have a similar developmental relationship.
      Although the literature in the past specifies mainly one option - to remove the
      crossbone - we consider several different options that one should think about
      before removal of the crossbones.

PMID- 15162314
TI  - Simplicity and treatment of the typical cleft hand.
AB  - The typical cleft hand is now distinguished from symbrachydactyly. This review of
      the surgical treatment of 108 hands in 63 patients treated over a 28-year period
      concentrates upon the technical principles of surgical correction. The key to
      these reconstructions is a wide incision which extends from the ulnar side of the
      cleft around the malpositioned index finger to the thumb. This wide exposure
      provides clear identification of all anatomic structures within the palm. There
      are no tenuous flaps with narrow random pedicles. These difficult surgical
      corrections may often include index transposition, metacarpal and/or phalangeal
      osteotomies, joint releases, phalangeal ostectomies, preservation of the adductor
      pollicis muscle, first dorsal interosseous muscle release, syndactyly
      separation(s) and thumb duplication correction. Following reposition of all
      skeletal structures the dorsal and palmar full-thickness flaps are easily
      contoured to create a satisfactory first webspace. Outcomes data shows that
      although the pinch and grip remain weak, these hands are quite functional. It is
      important that the repositioned index ray not interfere with gripping and
      precision maneuvers between the mobile thumb and the ulnar two digits (ring and
      small) of the hand.

PMID- 15162317
TI  - [Congenital unilateral muscular hyperplasia of the hand - a rare malformation].
AB  - This is a report on eight cases of a rare congenital malformation in the upper
      extremity, consisting of a unilateral muscular hyperplasia. In addition to the
      hand, all segments of the upper extremity may be affected. The hyperplasia is
      always unilateral, preferably on the right hand side, in combination with
      accessory muscles. Hereditary dependence or association with other malformations
      has not been observed. Six of eight patients were male. Shoulder and arm function
      were normal in all cases. Ulnar drift of the fingers in the metacarpophalangeal
      joints (six of eight patients), flexion contractures of the metacarpophalangeal
      joints (six of eight patients) and extension contractures of the wrist (three of
      eight patients) to various degrees were seen. A prominence of the second and
      third metacarpal head with an enlarged space between them gave the affected hands
      a very typical appearance (six of eight patients). Deformities and functional
      limitations requiring surgical treatment were present in six patients. In all
      cases, accessory muscles were found intraoperatively and resected. The
      macroscopic and microscopic appearance of the muscle specimen did not differ from
      normal muscular tissue. In all cases, additional procedures were necessary to
      improve the overall function. Nevertheless, the reconstructive efforts did not
      lead to an entirely normal hand function or appearance. The malformation we
      describe can clearly be distinguished from other malformations such as
      arthrogryposis multiplex congenita, Freeman-Sheldon syndrome or macrodactyly. Up
      to now, only two other reports were found in the literature showing
      characteristics similar to those in our own cases. Four similar cases were
      observed by Benatar. From a pathomechanical point of view, a disturbance in the
      muscular balance seems to cause the deformities and functional limitations. This
      imbalance could be related to accessory muscles which are not opposed by defined
      antagonists or to an unbalanced hyperplasia of normally developed musculature.
      Surgical intervention should begin early to prevent joint stiffness. Splinting
      and hand therapy should precede surgical intervention. Surgical treatment should
      aim to restore the muscular balance by resection of accessory and hyperplastic
      musculature. In some cases, muscle transpositions and joint releases may have to
      be performed. Postoperative splinting and intensive hand therapy are mandatory to
      preserve the results.

PMID- 15162318
TI  - Surgical management of the hand in Apert syndrome.
AB  - In patients with Apert syndrome, the hands demonstrate many disturbances of soft
      tissue and bony structures. These include a short thumb with radial clinodactyly,
      complex syndactyly with a bony fusion involving the index, long and ring fingers,
      symphalangism and simple syndactyly of the fourth web space. The soft tissue
      anomalies involve the intrinsic muscles, the extrinsic tendon insertions and the
      neurovascular bundles. We have reviewed 52 patients who underwent surgical
      reconstruction of their hands. The aim of this study is to propose a better
      surgical management in the light of recent publications and to improve our
      understanding of the syndrome, attempting to reduce the number of procedures and
      to select the best possible procedures for each patient.

PMID- 15162319
TI  - Full-thickness skin grafts from the cubital fossa for syndactyly-release.
AB  - In syndactyly-release, skin defects along the sides of the fingers are usually
      covered with full-thickness skin grafts harvested from the groin. Since January
      1997, we have been routinely harvesting full-thickness skin grafts from the
      cubital fossa instead. Skin grafts from the cubital fossa are softer and more
      pliable than those from the groin. Furthermore, they give a superior color match
      and cannot give rise to the growth of unsightly and embarrassing pubic hair in
      the hand. Donor-site morbidity seems to be nearly negligible, particularly if the
      donor site scar line is situated along one of the transverse skin creases of the
      cubital fossa. In cases of multiple syndactylies in a single hand, full-thickness
      skin grafts can be repeatedly harvested from the cubital fossa.

PMID- 15162320
TI  - Ten years CHASG, a combination of science and friendship.

PMID- 15162322
TI  - Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding
      protein cause nonsyndromic X-linked mental retardation.
AB  - Nonsyndromic X-linked mental retardation (NSXLMR) is a very heterogeneous
      condition, and most of the underlying gene defects are still unknown. Recently,
      we have shown that approximately 30% of these genes cluster on the proximal Xp,
      which prompted us to perform systematic mutation screening in brain-expressed
      genes from this region. Here, we report on a novel NSXLMR gene, FTSJ1, which
      harbors mutations in three unrelated families--one with a splicing defect, one
      with a nonsense mutation, and one with a deletion of one nucleotide. In two
      families, subsequent expression studies showed complete absence or significant
      reduction of mutant FTSJ1 transcripts. FTSJ1 protein is a homolog of Escherichia
      coli RNA methyltransferase FtsJ/RrmJ and may play a role in the regulation of
      translation. Further studies aim to elucidate the function of human FTSJ1 and its
      role during brain development.

PMID- 15162324
TI  - The Effect of Danazol Treatment on Factor IX Deficiency in Cats.

PMID- 15162325
TI  - A comparison of cytochemical techniques to demonstrate peroxidase activity in
      canine leukocytes.

PMID- 15162326
TI  - Studies on the pathogenesis of the erythrocyte destruction associated with the
      anemia of inflammatory disease.
AB  - Density-separated feline RBC were analyzed for surface immunoglobulin and in
      vitro susceptibility to macrophage phagocytosis before and after introduction of
      a sterile abscess. Prior to abscess induction, least dense cells did not have
      detectable surface immunoglobulin G (IgG) as a direct antiglobulin reaction was
      negative. Two of four intermediate and three of four most dense cell fractions
      had detectable surface IgG as indicated by a positive direct antiglobulin
      reaction. On Days 3 and 5 after induction of sterile abscesses all three RBC
      fractions were positive and the size of the RBC clumps tended to increase. In
      vitro macrophage phagocytosis of all three RBC fractions increased significantly
      after abscess induction. The phagocytosis could be partially blocked by
      preincubation of macrophages with feline IgG.

PMID- 15162327
TI  - The Effect of Diminazene Aceturate on Spienectomized Dogs with Babesia gibsoni
      Infection.
AB  - The effect of diminazene aceturate on splenectomized and nonspienectomized dogs
      with Babesia gibsoni (B. gibsoni) infection was investigated. In splenectomized
      dogs, the fissional and multiplicational stages of B. gibsoni were observed in
      peripheral blood films, and hemoglobinuria was frequently observed. These
      findings were different from previous reports and were not changed by
      administration of diminazene aceturate. It is clear that the intramuscular
      administration of diminazene aceturate at the dose of 3 mg/kg body weight for 3
      days is not effective against B. gibsoni infection in splenectomized dogs.

PMID- 15162328
TI  - Combined phagocytosis-nitroblue tetrazolium reduction test in bovine neutrophils.
AB  - An assay was developed for the simultaneous evaluation of phagocytosis and
      oxidative metabolism of bovine blood neutrophils. Phagocytosis was evaluated by
      using opsonized zymosan, and oxidative metabolism was evaluated by nitroblue
      tetrazolium (NBT) reduction. Normal bovine neutrophils exhibited moderate
      variation in ability to phagocytize zymosan, but little variation in ability to
      reduce NBT. The subcellular location of NBT reduction to formazan was determined
      by electron microscopy. Electron dense formazan precipitate was observed along
      the inner membrane of phagosomes enclosing zymosan particles and radiating from
      the membrane toward the center of the phagosome.

PMID- 15162323
TI  - Phylogeography of Y-chromosome haplogroup I reveals distinct domains of
      prehistoric gene flow in europe.
AB  - To investigate which aspects of contemporary human Y-chromosome variation in
      Europe are characteristic of primary colonization, late-glacial expansions from
      refuge areas, Neolithic dispersals, or more recent events of gene flow, we have
      analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny
      that is widespread over Europe but virtually absent elsewhere. The analysis of
      1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from
      60 population samples, revealed several subclades with distinct geographic
      distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a
      rapidly decreasing frequency toward both the East European Plain and the Atlantic
      fringe, but microsatellite diversity reveals that France could be the source
      region of the early spread of both I1a and the less common I1c. Also, I1b*, which
      extends from the eastern Adriatic to eastern Europe and declines noticeably
      toward the southern Balkans and abruptly toward the periphery of northern Italy,
      probably diffused after the Last Glacial Maximum from a homeland in eastern
      Europe or the Balkans. In contrast, I1b2 most likely arose in southern
      France/Iberia. Similarly to the other subclades, it underwent a postglacial
      expansion and marked the human colonization of Sardinia approximately 9,000 years
      ago.

PMID- 15162329
TI  - Correction for sample free glycerol is needed for accurate measurement of plasma
      triglyceride concentrations in miniature Swine.
AB  - Methods for the measurement of plasma or serum triglyceride concentrations
      usually quantify the glycerol released by enzymatic hydrolysis of the
      triglyceride molecule. Any free glycerol in the sample is measured erroneously as
      triglyceride in these methods. As miniature swine have been used commonly for
      comparative studies of plasma lipoprotein lipids, this study was conducted to
      assess the need for free glycerol correction of plasma triglyceride measurements
      by comparing glycerol-blank corrected and non-corrected total plasma triglyceride
      concentrations from fasted minipigs. Fasting plasma free glycerol concentrations
      range from 9 to 14 mg/dl. The mean +/- SD (n = 16) glycerol-blank corrected total
      plasma triglyceride value (77 +/- 8 mg/dl) was significantly (p < 0.001) less
      than the uncorrected measurement value (189 +/- 12 mg/dl). Poor correlation (r =
      0.24) between corrected and uncorrected total plasma triglyceride measurements
      suggests that mathematic correction by a constant correction factor would yield
      inaccurate results for miniature swine. Free glycerol blanking is essential for
      determination of the true total plasma triglyceride concentration.

PMID- 15162330
TI  - Comparison of Various Staining Procedures in the Identification of Hepatozoon
      canis Gamonts.
AB  - The staining characteristics of gamonts of Hepatozoon canis in peripheral blood
      smears were evaluated. Three stains, Diff-Quik stain, Giemsa stain and a
      modification of the naphthol-ASD-chloroacetate esterase stain, were compared. The
      staining characteristics of the infected cell and the parasite were different in
      each stain used. The modified naphthol-ASD-chloroacetate esterase stain showed
      the most difference between the infected and noninfected cells, as well as a
      difference in staining characteristics of the parasite nucleus from those of the
      host nucleus. Although the parasite was identified with all stains, a definitive
      diagnosis was more easily obtained with the naphthol-ASD-chloroacetate esterase
      stain.

PMID- 15162331
TI  - A Technique for Automated Quantification of Canine Glucocorticoid-induced
      Isoenzyme of Alkaline Phosphatase.
AB  - A sensitive assay for the corticosteroid-induced alkaline phosphatase isoenzyme
      (CAP), adaptable to most clinical chemistry autoanalyzers, is described and
      validated. This assay is based on the greater than 98% inhibition of liver
      alkaline phosphatase isoenzyme (LAP) activity with 4.2 mM levamisole, as compared
      to the 42% inhibition of CAP activity. Analysis of serum with total alkaline
      phosphatase (AP) activity within the reference range, resulted in a reference
      range of 0 to 19 U/L for CAP activity. Analysis of serum from 160 clinical
      patients with AP activity above the reference range, revealed 73% with increased
      CAP activity ranging from 20 to 7,000 U/L. The diagnostic significance of this
      increased CAP activity is discussed.

PMID- 15162333
TI  - Susceptibility of canine, feline and human erythrocytes to oxidant-mediated
      injury.
AB  - e relative susceptibilities of feline, canine and human erythrocytes to in vitro
      hydrogen peroxide-induced lipid peroxidation and hemolysis were studied. At 15
      minutes following exposure to hydrogen peroxide, cat erythrocytes had higher
      concentrations of lipid peroxidation by-products and a greater percent hemolysis
      as compared to dogs and humans. Erythrocytes from cats with induced sterile
      abscesses had lower concentrations of the antioxidant glutathione, but they did
      not have detectable concentrations of lipid peroxides nor were they more
      susceptible to in vitro lipid peroxidation or hemolysis.

PMID- 15162332
TI  - Serum bile acids: reference values in healthy dogs and comparison of two kit
      methods.
AB  - Serum bile acid (SBA) reference intervals were established by use of a
      radioimmunoassay method for fasting dogs to be 0.2 to 4.3 micro mol/L (n = 60)
      and for 2 hour postprandial samples to be 0.6 to 24.2 micro mol/L (n = 37). The
      SBA reference intervals estimated using an enzymatic method were 0 to 8.6 micro
      mol/L for fasting (n = 26) and 0 to 29.8 micro mol/L for 2 hour postprandial
      samples (n = 36). The correlation between the two methods including samples from
      healthy dogs and clinical cases is good (n = 128, r = 0.82, p < 0.0001). The
      radioimmunoassay method is linear to 50 micro mol/L and the enzymatic method is
      linear to 100 micro mol/L, thus both methods require serum dilutions to be made
      in many cases of primary liver disease. The enzymatic method is less expensive
      and more convenient for use in a clinical laboratory but requires a greater
      sample volume (400 micro I) than the RIA method (50 micro I). Both methods have
      adequate precision and accuracy to be useful as diagnostic tests of liver
      function in dogs.

PMID- 15162334
TI  - Effect of age on serum chemistry profile, electrophoresis and thyroid hormones in
      beagle dogs two weeks to one year of age.
AB  - Chemistry tests were conducted on serum from young Beagle dogs in order to deter
      mine the effect of age on these parameters. Blood was collected at regular
      intervals from 25 normal Beagle puppies (13 males and 12 females) at ages ranging
      from 2 weeks to 12 months. Serum chemistry profiles, protein electrophoresis and
      radioimmunoassays for thyroxine and triiodothyronine were included. Rapidly
      changing age related differences were observed in several parameters. Urea
      nitrogen, cholesterol, triglycerides, lactate dehydrogenase, thyroxine, glucose,
      gamma glutamyl transpeptidase, and total bilirubin values were elevated early in
      life, and decreased during the first 6 to 8 weeks, while alanine aminotransferase
      activity was low initially and increased during this period. Lactate
      dehydrogenase, thyroxine, gamma glutamyl transpeptidase, total bilirubin and
      alanine aminotransferase attained stability by 3 months, but the remaining
      parameters showed slight changes subsequently, gradually approaching adult
      values. More gradual age related changes were observed in other parameters. These
      included alkaline phosphatase, inorganic phosphorus and calcium values, which
      were higher in younger dogs, and creatinine, aspartate aminotransferase and total
      protein values, which were lower in younger dogs. Creatinine and aspartate
      aminotransferase values were stable by approximately 6 months; alkaline
      phosphatase, inorganic phosphorus, calcium and total protein values continued to
      change gradually up to 1 year.

PMID- 15162335
TI  - Methemalbumin: reality and myth.
AB  - The ability to form methemalbumin by binding oxidized heme is described
      frequently as a characteristic of albumin from all animal species. Actually, only
      albumin from a limited number of species makes methemalbumin. Lack of recognition
      of interspecies differences has led to the myth of methemalbumin in domestic
      animals. The literature on methemalbumin is reviewed including the chemical
      characteristics of true methemalbumin and the misuse of mythical methemalbumin.

PMID- 15162336
TI  - Automated Blood Cell Counting Systems: A Comparison of the Coulter S-Plus IV,
      Ortho ELT-8/DS, Ortho ELT-8/WS, Technicon H-1, and Sysmex E-5,000.
AB  - Four automated blood cell counting systems were evaluated at the Michigan State
      University Veterinary Clinical Center (VCC) for their suitability for analyzing
      various animals' blood in a university teaching hospital laboratory. The
      instruments were compared to a Coulter Model S-Senior (Coulter Electronics)which
      had been used for 8 years, and was to be replaced. The instruments were a Coulter
      Model S-Plus IV, an Ortho ELT-8/ds (Ortho Diagnostics Systems), a Technicon H-1
      (Technicon Instruments), and a Sysmex E-5,000 (Toa Medical Electronics).
      Additionally, an Ortho ELT-8/ws at a private laboratory (Cenvet) was compared to
      the Coulter S-Senior at the VCC. Based on these evaluations, only the Sysmex E
      5,000 was considered unacceptable for the VCC laboratory. Certain advantages and
      disadvantages of the instruments are described in this article. The comparisons
      among instruments were not as consistent or repetitive as expected for a
      controlled experiment but did provide information likely useful to others
      considering using or purchasing an automated blood cell counting system for a
      veterinary laboratory.

PMID- 15162337
TI  - Estimating platelets and leukocytes on canine blood smears.

PMID- 15162338
TI  - What is your diagnosis?

PMID- 15162339
TI  - Oral Mucosa Bleeding Times of Normal Cats and Cats with Chediak-Higashi Syndrome
      or Hageman Trait (Factor XII Deficiency).
AB  - A commercially available, disposable blade in a spring-loaded cassette was used
      to measure oral mucosa bleeding times (OMBT) of ketamine/acepromazine
      anesthetized cats. The OMBT were determined in cats homozygous for Chediak
      Higashi syndrome (CHS, n = 7), cats heterozygous for CHS (n = 6), and cats
      homozygous for Hageman factor (factor XII) deficiency (n = 5). In addition, OMBT
      were determined in three groups of normal cats: random-source cats (n = 14),
      inbred normal relatives of the cats with CHS (n = 7), and inbred normal relatives
      of Hageman factor deficient cats (n = 9). No significant differences were found
      in the OMBT of the three groups of normal cats. The mean OMBT for all 30 normal
      cats was 1.9 minutes +/- 0.5 minutes s.d. Compared to the normal cats, those
      homozygous for CHS had significantly prolonged OMBT (14.1 +/- 3.3 minutes; p <
      0.05). The mean OMBT of cats heterozygous for CHS (2.6 +/- 0.8 minutes) was also
      significantly longer than the OMBT of the combined normal group. The mean OMBT of
      the CHS heterozygotes, however, was not significantly longer than that of their
      normal relatives (OMBT = 1.8 +/- 0.5 minutes), probably because of the low number
      of cats in this subgroup of normals. As expected, the OMBT of cats homozygous for
      Hageman factor deficiency (2.3 +/- 0.3 minutes) were not significantly prolonged.

PMID- 15162340
TI  - What is your diagnosis?

PMID- 15162341
TI  - Direct measurement of progesterone in plasma and milk by a simple solid-phase
      radioimmunoassay.
AB  - A rapid method for determination of progesterone in bovine, goat and porcine
      plasma as well as in bovine milk was evaluated. The method employed was a solid
      phase (125)I radioimmunoassay equipped with progesterone standards in human serum
      and called the Coat-A-Count procedure. The dilution curves of bovine plasma
      samples with high progesterone content were parallel with the standard curve
      based on human serum. The relation between measurements of progesterone levels in
      bovine plasma using the reference extraction method and the direct Coat-A-Count
      procedure was highly significant, resulting in the linear regression equation Y =
      1.06x-0.04. In case of goat and porcine plasma, the direct method yielded higher
      results than the reference extraction method (Y = 1.37x + 1.38 and Y = 1.69x -
      6.47, respectively). Progesterone concentration in bovine whole milk was much
      higher when measured by the Coat-A-Count procedure than by the reference Farmos
      kit (Y = 1.59x + 1.51). However, when the same samples were assayed by a modified
      Coat-A- Count procedure, i.e. progesterone standards from Farmos kit, the values
      were more or less identical (Y = 0.88x - 0.21).

PMID- 15162342
TI  - Psychological aspects of persistent pain: current state of the science.
AB  - This article provides an overview of current research on psychological aspects of
      persistent pain. It is divided into 3 sections. In section 1, recent studies are
      reviewed that provide evidence that psychological factors are related to
      adjustment to persistent pain. This section addresses research on factors
      associated with increased pain and poorer adjustment to pain (ie, pain
      catastrophizing, pain-related anxiety and fear of pain, and helplessness) and
      factors associated with decreased pain and improved adjustment to pain (ie, self
      efficacy, pain coping strategies, readiness to change, and acceptance). In
      section 2, we review recent research on behavioral and psychosocial interventions
      for patients with persistent pain. Topics addressed include early intervention,
      tailoring treatment, telephone/Internet-based treatment, caregiver-assisted
      treatment, and exposure-based protocols. In section 3, we conclude with a general
      discussion that highlights steps needed to advance this area of research
      including developing more comprehensive and integrative conceptual models,
      increasing attention to the social context of pain, examining the link of
      psychological factors to pain-related brain activation patterns, and
      investigating the mechanisms underlying the efficacy of psychological treatments
      for pain. PERSPECTIVE: This is one of several invited commentaries to appear in
      The Journal of Pain in recognition of The Decade of Pain Research. This article
      provides an overview of current research on psychological aspects of persistent
      pain, and highlights steps needed to advance this area of research.

PMID- 15162343
TI  - The distribution of hyperaemia induced by skin burn injury is not correlated with
      the development of secondary punctate hyperalgesia.
AB  - This study in 20 volunteers examines whether changes in cutaneous blood flow
      distribution (laser Doppler flow scanning, LDS) and visible flare correlate in
      time and in distribution with the development of secondary hyperalgesia (SH,
      punctate stimulation of a 45-g von Frey filament) induced by a superficial skin
      burn injury. Areas of LDS and flare were at their largest at 5 minutes after the
      burn injury (58 +/- 30 and 20 +/- 11 cm2, respectively), whereas the largest area
      of SH was seen after 60 minutes (50 +/- 45 cm2). Although the maximum areas of
      LDS and SH were of the same magnitude, the blood flow response was essentially
      abolished when the maximal SH area was noticed at 60 minutes. Furthermore, on an
      individual basis, there was no correlation between the size of maximal LDS area
      (at 5 minutes) and maximal SH area (at 60 minutes) (r = 0.27; P =.26). Therefore,
      peripheral mechanisms associated with the neurogenic inflammation reaction
      surrounding a skin burn injury are not directly associated with the induction of
      SH. PERSPECTIVE: Tissue trauma and inflammation-induced sensory abnormalities are
      important because they are involved in acute nociceptive pain, as well as in
      chronic pain conditions. This study notes the significance of central
      sensitization for the development of secondary hyperalgesia, an important
      phenomenon underlying many clinical pain conditions.

PMID- 15162344
TI  - Smoking and smokeless tobacco: increased risk for oral pain.
AB  - Tobacco has been linked with several pain conditions that include musculoskeletal
      pain, rheumatoid arthritis, and fibromyalgia. This study documented associations
      between smoking and smokeless tobacco use and measures of orofacial pain and oral
      pain impacts (activity reduction and trouble with sleep) assessed during a 48
      month time period. These data were collected as part of the Florida Dental Care
      Study, a longitudinal study of oral health among 873 adults aged 45 years and
      older at baseline. Twenty-five percent of the study participants were current
      users of some form of tobacco, and 34% were former users. Separate models were
      tested for smoking and smokeless tobacco. Current tobacco users were at increased
      risk of experiencing a range of painful oral symptoms. We also found that
      behavioral impacts associated with oral pain are sensitive to differences in
      tobacco use status. Our data also support the supposition that once tobacco
      cessation occurs, the risk for pain associated with oral disease decreases
      significantly. No differences were found between former users and those never
      having used tobacco across any of the pain measures. Strengths of the current
      study include the longitudinal methodology, assessment of different pain symptoms
      with potentially differing etiology, and that several markers of tobacco use were
      used (prevalence, consumption, and duration). PERSPECTIVE: This study considers
      the harmful effects of tobacco use on oral health. Smokers were at significantly
      increased risk for oral pain and related limitation of daily activities. The data
      also suggest that the risk for oral pain associated with tobacco use decreases
      significantly if tobacco cessation occurs.

PMID- 15162345
TI  - Association between quantitative sensory testing, treatment choice, and
      subsequent pain reduction in vulvar vestibulitis syndrome.
AB  - The chronic pain syndrome of vulvar vestibulitis is a major cause of sexual
      dysfunction, and complete cure is not always achieved. The aim of the study was
      to determine whether the psychophysical characteristics of systemic pain
      perception predict treatment choice and outcome. Ninety women with vulvar
      vestibulitis syndrome were evaluated by using quantitative sensory testing with
      heat pain threshold measurements and pain scores for suprathreshold stimuli
      applied to the forearm, blood pressure measurements, and an assessment of the
      number of other pain disorders. Women were free to choose a surgical procedure
      (ie, vestibulectomy), one of the possible nonsurgical treatments (eg,
      biofeedback, cognitive-behavioral therapy, or hypoallergic agents), or to avoid
      treatment entirely. Eight months later, women reported the success of the
      treatment on the basis of reduction in the level of vulvar pain. Vestibulectomy
      demonstrated the best therapeutic effectiveness (chi2, 26.4; P <.0001). Women who
      chose this type of treatment had lower pain scores (P =.038) and fewer pain
      syndromes other than the vulvar pain (P =.025). Logistic regression analysis,
      controlling for the effect of vestibulectomy, indicated that lower experimental
      pain scores (P =.044), fewer pain disorders (P =.023), and higher systolic blood
      pressure (P =.039) are predictive variables for reduction of vulvar pain. An
      assessment of systemic pain perception might be helpful in choosing the optimal
      treatment and in predicting its success. PERSPECTIVE: The present study suggests
      that pain perception variables might be of value in the prediction of treatment
      choice and outcome among women with vulvar vestibulitis.

PMID- 15162346
TI  - Temperature and the cold pressor test.
AB  - As a method of experimental pain induction, the cold pressor test is thought to
      mimic the effects of chronic conditions effectively. A survey of previous studies
      using the cold pressor, however, revealed a lack of standardization and control
      of water temperature, questioning comparability and reliability. This study
      reports the influence of temperature on pain tolerance and intensity by using a
      commercially available circulating water bath. Twenty-six participants (12 men,
      14 women) underwent 4 cold pressor trials with temperature order counterbalanced
      across 1 degrees C, 3 degrees C, 5 degrees C, and 7 degrees C, temperatures
      representative of the range used in previous literature. After each cold
      immersion participants rated pain intensity on a visual analogue scale and the
      McGill Pain Questionnaire. Tolerance times were recorded for each trial.
      Significant main effects of temperature were found for tolerance time, with
      higher temperatures resulting in longer times, and pain intensity, with lower
      temperatures resulting in higher intensities. Gender differences were found, with
      men tolerating the stimulus for significantly longer than women. It was concluded
      that small differences in water temperature have a significant effect on pain
      intensity and tolerance time. The use of cold pressor equipment that ensures a
      precise constant temperature of circulating water is necessary to ensure
      comparable and reliable results. PERSPECTIVE: The cold pressor method of
      experimental pain induction has been widely used in the evaluation of
      psychological and physiological pain treatments. This article highlights the need
      for clear methodologic guidelines for the technique and demonstrates that very
      minor changes in experimental protocol can produce significant differences.

PMID- 15162347
TI  - Botulinum toxin a for vulvodynia: a case report.
AB  - Vulvodynia is a poorly understood chronic pain condition, and patients who are
      refractory to standard therapies often pose a therapeutic dilemma. Current
      treatment modalities include antidepressants, anticonvulsants, biofeedback,
      pelvic floor physical therapy, and surgery; however, the options are limited for
      patients who fail to respond to these treatments. We present a case of refractory
      vulvodynia with severe dyspareunia successfully managed with a novel therapeutic
      approach combining botulinum toxin A and surgery. PERSPECTIVE: The authors
      present a case of refractory vulvodynia that was successfully managed with a
      novel approach that combined botulinum toxin A and surgery.

PMID- 15162348
TI  - Transoral carbon dioxide laser microsurgery for recurrent glottic carcinoma after
      radiotherapy.
AB  - BACKGROUND: Transoral laser microsurgery is successfully performed in the
      treatment of primary laryngeal carcinomas. Few publications deal with the
      application in patients with recurrent glottic carcinomas after radiation
      failure. Our study aims to review our experience with transoral laser
      microsurgery in these patients. METHODS: Thirty-four patients with early and
      advanced recurrent glottic carcinoma after full-course radiotherapy (rT1, n = 11;
      rT2, n = 10; rT3, n = 10; rT4, n = 3) had CO(2) laser treatment with curative
      intent between 1987 and 1998. RESULTS: Twenty-four patients (71%) were cured with
      one or more laser procedures. In nine patients, recurrences could not be
      controlled by laser microsurgery: six patients underwent total laryngectomy and
      three palliative treatment. One patient received total laryngectomy because of
      chondronecrosis after laser treatment. With a median follow-up interval of 38.6
      months, the 3-year and 5-year disease-specific survival was 86%. The overall 3
      year survival rate was 74%; the corresponding 5-year survival rate was 53%. No
      major complications occurred. In three cases, temporary tracheostomy was needed.
      CONCLUSIONS: In early-stage and advanced-stage recurrent glottic carcinomas after
      radiotherapy, CO(2) laser treatment can successfully be used as a curative organ
      preserving procedure. Compared with salvage laryngectomy, results are superior
      with respect to preservation of laryngeal function. Great expertise is required,
      especially in resections of advanced-stage recurrent carcinomas.

PMID- 15162349
TI  - High-dose superselective intra-arterial cisplatin and concomitant radiation
      (RADPLAT) for advanced head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to study the effect of intensive
      targeted chemoradiation in a group of patients with head and neck cancer with
      stage IV inoperable disease. METHODS: We examined 79 patients with inoperable
      stage IV head and neck cancer receiving intra-arterial infusion of high-dose
      cisplatin (150 mg/m(2)) on days 2, 9, 16, and 23 concomitant with delivery of
      external beam radiotherapy (total dose, 70 Gy; 2 Gy, 35 fractions; 1 fraction/day
      for 7 weeks). Sodium thiosulfate was administered intravenously to provide
      effective cisplatin neutralization. RESULTS: Four patients were not assessable.
      Complete local tumor response was achieved in 72 patients (91%) and a partial
      response in three patients. The complete response rate of neck node metastases
      was 90%. The 1- and 2-year locoregional control rates were 82% and 69%,
      respectively. The median overall survival time was 2.2 years, with a 3-year
      overall survival probability of 43%. Acute toxicities were as follows: grade
      III/IV hematologic toxicity (22%/16%), grade III/IV nephrotoxicity (0%), grade
      III mucositis (43%), grade III skin reactions (24%), grade III toxicity of the
      upper gastrointestinal tract (57%), grade III nausea (20%), and grade III
      subjective hearing loss (10%). Grade V toxicity (treatment-related deaths) was
      3.8%. Six (18%) of 33 patients with complete remission needed tube feeding 2
      years after treatment without intercurrent salvage surgery. CONCLUSIONS:
      Supradose superselective intra-arterial cisplatin and concomitant radiation is an
      effective organ-preserving therapy in an unfavorable group of patients. Our
      series confirms encouraging results reported previously. This regimen is
      justified in unresectable patients despite the substantial toxicity.

PMID- 15162350
TI  - Constitutive expression of interleukin-18 in head and neck squamous carcinoma
      cells.
AB  - BACKGROUND: Interleukin (IL)-18 is a potent immunomodulatory cytokine promoting
      TH-1 and cytotoxic immune responses through interferon (IFN)-gamma induction. The
      aim of this study was to investigate the production of IL-18 by squamous cell
      carcinoma of the head and neck (HNSCC). METHODS: The expression of IL-18 was
      analyzed by reverse transcriptase-polymerase chain reaction, Western blot, and
      ELISA in untreated and 5-fluorouracil (5-FU)-treated HNSCC cell lines.
      Immunohistochemical analysis was performed on tumor specimens from 16 patients
      with primary invasive HNSCC. RESULTS: We have demonstrated that HNSCC cell lines
      express IL-18 at the mRNA, as well as the protein, level. However, the IL-18
      protein was expressed intracellularly and predominantly released as an
      unprocessed inactive 24-kDa form. After exposure to 5-FU, the processed form of
      IL-18 was detected in the supernatants of both HNSCC cell lines. CONCLUSIONS:
      These results indicate that HNSCC cells are a potential source of IL-18 cytokine.
      The finding that the exposure to 5-FU can elicit its processing suggests a novel
      target for immunomodulatory intervention in patients with HNSCC.

PMID- 15162351
TI  - Telomerase as an independent prognostic factor in head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: Telomerase activity has been found to be associated with many
      cancers, including head and neck squamous cell carcinoma (HNSCC). We examined the
      association of telomerase activity with the clinical outcome of patients with
      HNSCC. METHODS: A PCR-based enzyme immunoassay method was used to measure
      telomerase activity in 217 matched (grossly normal and cancerous) tissues from
      patients with HNSCC. Pearson chi-square test was used to analyze the correlation
      of telomerase activity with clinicopathologic parameters. Kaplan-Meier method and
      Cox logistic regression model were used for prognostic analysis. RESULTS: Of the
      217 tissues assayed, 4.1% of the normal and 63.3% of the cancer tissues had high
      levels of telomerase activity. Telomerase activity was shown to be statistically
      correlated with extracapsule spreading (ECS) of lymph nodes (p =.005) and overall
      survival (p =.003). On multivariant analysis, overall stage (p =.007), tumor
      depth (p =.045), and telomerase activity (p =.008) showed independent variables
      associated with poor survival. CONCLUSIONS: Telomerase activity has been shown to
      be an independent prognostic factor for survival in cases of HNSCC. Telomerase
      may be a potential molecular target for clinical use in prognostication and
      therapy in cases of the disease.

PMID- 15162352
TI  - Previous chemotherapy as a predictor of wound infections in nonmajor head and
      neck surgery: Results of a prospective study.
AB  - BACKGROUND: The goal of this prospective study was to determine the incidence of
      wound infections (WI) after clean uncontaminated head and neck cancer procedures
      and after emergency tracheotomies. METHODS: Two hundred twelve clean procedures
      without tracheotomy or opening of mucosa (neck dissections, large skin
      resections, thyroidectomies, parotid gland resections, and explorative
      cervicotomies) were studied at Oscar Lambret Cancer Center over a 24-month
      period. RESULTS: WI rate was 6.6% (14 of 212). In a univariate analysis, only one
      variable was significantly related to the likelihood of WI: previous anticancer
      chemotherapy. All but one patient who had had previous chemotherapy demonstrated
      WI (14 of 15). CONCLUSIONS: After previous chemotherapy, WI rate in clean
      uncontaminated head and neck surgery was as high as 90%. In this case, antibiotic
      prophylaxis should be evaluated.

PMID- 15162353
TI  - A pilot study of a randomized controlled trial to evaluate the effects of
      progressive resistance exercise training on shoulder dysfunction caused by spinal
      accessory neurapraxia/neurectomy in head and neck cancer survivors.
AB  - BACKGROUND: Shoulder dysfunction remains a frequent complication after neck
      dissection procedures for head and neck cancer. METHODS: We conducted a pilot
      study to evaluate the effects of progressive resistance exercise training (PRET)
      on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in
      patients with head and neck cancer. Twenty patients (mean age, 61 +/- 7.7 years)
      were randomly assigned to PRET or standard care intervention. Subjects assigned
      to the PRET group exercised three times per week for 12 weeks. The goal of the
      exercise program was to enhance scapular stability and strength of the upper
      extremity. The resistance-training program was progressive in terms of number of
      sets and repetitions performed, as well as the amount of weight lifted, depending
      on performance status. RESULTS: The completion rate for the trial was 85% (17 of
      20). The exercise group completed 93% of scheduled exercise sessions. Significant
      improvements were found in favor of the PRET group in active shoulder external
      rotation (p =.001), shoulder pain (p =.038), and overall score for shoulder pain
      and disability (p =.045). CONCLUSIONS: The study results demonstrate a high rate
      of completion and adherence with our PRET program among patients with head and
      neck cancer. The preliminary findings, although limited, also suggest a potential
      therapeutic role for resistance exercise as an adjunct to standard physical
      therapy treatment.

PMID- 15162354
TI  - Facial node involvement in head and neck cancer.
AB  - BACKGROUND: Facial node involvement in head and neck cancer is rarely documented.
      Furthermore, facial node removal may increase the risk of damage to the marginal
      mandibular nerve. Thus, although they may receive afferent lymphatic drainage
      from the oral cavity, facial nodes are rarely removed during neck dissection.
      METHODS: We retrospectively reviewed the records of 29 patients with oral cavity
      or oropharyngeal carcinomas who underwent facial node sampling in 32 heminecks
      during neck dissection for oral cavity or oropharyngeal cancer. RESULTS: Facial
      node metastases were present in seven patients. Facial node involvement was much
      more common among patients with palpable cervical lymphadenopathy. Positive
      facial nodes were associated with an increased risk of treatment failure and a
      poorer survival. CONCLUSIONS: In patients with oral cavity/oropharyngeal primary
      tumors and palpable cervical lymphadenopathy, consideration should be given to
      removal of facial nodes during neck dissection; however, further data are awaited
      before any benefits can be quantified.

PMID- 15162355
TI  - End-to-side venous anastomosis with the internal jugular vein stump: a
      preliminary report.
AB  - BACKGROUND: Failure of free flaps is frequently because of failure of the venous
      vascular anastomosis. A new venous anastomosis technique that uses the stump of
      the internal jugular vein (IJV) is described, with preliminary data on operative
      outcomes. METHODS: Retrospective analysis of eight head and neck free flap
      operations in which a venous anastomosis to the stump of an IJV was used compared
      with 222 other free flap operations in the same period (1995-2001) at a single
      institution. RESULTS: None of the eight free flaps that used venous end-to-side
      anastomoses to the stump of an IJV failed. There were 15 failures associated with
      the other 222 venous microvascular anastomoses (6.8%). CONCLUSIONS: This new
      technique resulted in no failures in eight operations. Advantages of this
      technique include avoiding creating an anastomosis under tension or requiring a
      saphenous vein graft and reducing pedicle torsion at the hilum of the flap.

PMID- 15162356
TI  - Tracheal mucormycosis presented as an intraluminal soft tissue mass.
AB  - BACKGROUND: Mucormycosis is a potentially lethal disease caused by an
      opportunistic fungal infection. It occurs mostly in diabetic or immunosuppressed
      patients and usually involves the lungs or paranasal sinuses. METHODS: We report
      a rare case of a patient with diabetic ketoacidosis who presented with
      progressive cough and dyspnea. CT of the neck and chest showed an intraluminal
      soft-tissue mass extending from the first tracheal ring to the thoracic inlet,
      causing severe destruction of the trachea. Direct laryngoscopy and biopsy
      demonstrated hyphal invasion with architecture typical of invasive mucormycosis.
      RESULTS: The patient underwent resection of the upper trachea and prolonged
      amphotericin B therapy and is disease free at 24 months after surgery.
      CONCLUSIONS: In patients with diabetes presenting with progressive hoarseness,
      dyspnea, and endobronchial mass, a fungal infection should be considered. In case
      of invasive tracheal mucormycosis, prompt diagnosis and early surgical resection
      may help improve survival.

PMID- 15162357
TI  - Lipomatous hemangiopericytoma of the head and neck: immunohistochemical and DNA
      ploidy analyses.
AB  - BACKGROUND: Lipomatous hemangiopericytoma (LHPC) is a newly described rare soft
      tissue tumor with unpredictable biologic behavior and is difficult to diagnose by
      conventional histologic parameters. The molecular analyses of this entity to date
      are sparse. Only a few cases of LHPC have been reported. Although one case of
      LHPC in the sinonasal region was briefly reported, this is the first case in the
      head and neck region with detailed clinicopathologic features and molecular
      analysis of this entity. METHODS: We reported a case of LHPC in a 55-year-old
      woman with a slowly growing lesion in the occipital area that was diagnosed by CT
      and MRI and removed surgically. Immunohistochemical and DNA ploidy analyses were
      performed. RESULTS: A panel of 16 markers was included for immunohistochemical
      analysis. Diffuse immunopositivity of CD57 in our case provides supportive
      evidence that LHPC is linked with HPC because this marker is also present in
      approximately 50% of conventional HPCs. CD57 should be used in the
      immunohistochemical panel in any lesion suspected to be LHPC. Furthermore, CD57
      along with CD34 and XIIIa is thought to stain for primitive mesenchymal stem
      cells, suggesting a bimodal/multimodal differentiation of LHPC. By flow
      cytometry, we found that tumor cells were 100% diploid with the S-phase fraction
      (SPF) being 3.21%. A significant positive correlation was detected between
      nuclear proliferating index and SPF (p < 0.001, by Spearman analysis). These
      findings provide molecular evidence indicating a benign nature of LHPC.
      CONCLUSIONS: Contrary to the old belief that HPC has an aggressive nature, this
      variant of tumor looks less aggressive. The patient was followed for 1 year
      without any evidence of recurrence, supporting our pathologic hypothesis.

PMID- 15162358
TI  - Lingual abscess: diagnosis and treatment.
AB  - BACKGROUND: Lingual abscesses are very rare, and as a result, the individual
      surgeon usually lacks experience in the diagnosis and therapy of this entity. We
      present four cases of abscesses of the tongue diagnosed and treated during the
      past 2 years. METHODS: The medical records, films, and charts of four patients
      with lingual abscess were retrospectively reviewed. The clinical presentation,
      radiographic features, treatment, and outcome of the cases were examined.
      RESULTS: Diagnosis was obtained by clinical examination and CT. In all cases, we
      avoided incision and drainage and preferred draining the abscess and aspirating
      pus with a large-bore needle through the inferior surface of the tongue. All
      patients responded remarkably well and did not have any recurrence. CONCLUSIONS:
      Lingual abscesses are rare conditions. In contrast to the approach in cases of
      most deep neck space infections, a more conservative therapeutic approach by
      needle-aspiration is effective and has the advantages of not exacerbating the
      edema of the tongue and of avoiding airway compromise.

PMID- 15162359
TI  - Advances in chemistry and bioactivity of the genus Uncaria.
AB  - The alkaloids of the pantropical genus Uncaria (Rubiaceae) were reviewed
      extensively by Phillipson et al. in (1978) Since then a host of papers with new
      results has been published. The compounds discovered are from three major groups:
      (1) alkaloids; (2) terpenoids; and (3) flavonoids. Some highly unusual structures
      have been reported. Although there are at least 35 species of Uncaria known,
      recent research focussed on a relatively small number of species. During recent
      years bioactivity of extracts and pure compounds isolated from Uncaria species
      have been increasingly investigated. These include anticonvulsive,
      antiinflammatory, antimutagenic, antioxidant, cytoprotective, hypotensive, and
      immunoregulatory effects. The literature since 1978 is reviewed and 133
      references are given.

PMID- 15162360
TI  - Bioactive brominated diterpenes from the marine red alga Jania Rubens (L.) Lamx.
AB  - Seven brominated diterpenes of the parguerene and isoparguerene series were
      isolated for the first time from the red alga Jania rubens (L.) Lamx., collected
      from the Red Sea coast at Hurghada, Egypt. The diterpenes were identified as
      isoparguerol (1), isoparguerol-16-acetate (2), isoparguerol-7,16-diacetate (3),
      parguerol-16-acetate (4), parguerol-7,16-diacetate (5), deoxyparguerol (6) and
      deoxyparguerol-7-acetate (7). The isolated diterpenes had a marked antitumour
      activity. Isoparguerol derivatives were slightly more effective than parguerol
      derivatives. Moreover, the data implied that the cytotoxicity of these compounds
      were dependent on the number of acetoxy groups. Also, anthelmintic activities of
      the isolated compounds on earthworms (Allolobophora caliginosa) were studied.

PMID- 15162361
TI  - Protective effects of selected medicinal plants against protein degradation,
      lipid peroxidation and deformability loss of oxidatively stressed human
      erythrocytes.
AB  - The effects of seven medicinal plants including Artemisia herba-alba, Ferula
      hermonis, Hibiscus sabdariffa, Nigella sativa, Teucrium polium, Trigonella foenum
      graecum, and Allium sativum on protein degradation, lipid peroxidation,
      erythrocyte deformability and osmotic fragility of erythrocytes exposed in vitro
      to 10 mM H(2)O(2) for 60 min at 37 degrees C have been examined. Preincubation of
      erythrocytes with Nigella sativa and Allium sativum protected erythrocytes
      against protein degradation, loss of deformability and increased osmotic
      fragility caused by H(2)O(2), while the other plants failed to protect
      erythrocytes against these damages. Artemisia herba-alba did not protect
      erythrocytes against lipid peroxidation, while Trigonella foenum-graecum
      unexpectedly increased lipid peroxidation of erythrocytes exposed to H(2)O(2).
      Ferula hermonis, Hibiscus sabdariffa, Nigella sativa, Teucrium polium and Allium
      sativum protected erythrocytes against lipid peroxidation. The results indicate
      the importance of oxidatively damaged cellular proteins in compromising the
      rheologic behaviour of the erythrocytes, and that the medicinal plants which have
      anti-protein-oxidant activity (e.g. Nigella sativa and Allium sativum) could be
      rheologically useful, particularly in pathological conditions related to free
      radicals.

PMID- 15162362
TI  - Ultrastructural changes in the testis and epididymis of rats following treatment
      with the benzene chromatographic fraction of the chloroform extract of the seeds
      of Carica papaya.
AB  - The benzene chromatographic fraction of the chloroform extract of the seeds of
      Carica papaya at a dose of 10 mg/rat/day for 150 days, which has shown a total
      inhibition of motility, reduced sperm count and infertility, was tested to de fi
      ne the mode of action at the subcellular level in the testis and epididymis. The
      ultrastructure of the testis of the treated animals revealed no appreciable
      changes in the subcellular characteristics. The mechanism of protein synthesis as
      well as steroidogenesis were evident in the Sertoli cells while the
      spermatogonia, spermatocytes and spermatids, both round and elongated, depicted a
      prominent nucleus, distinct nuclear membrane and cytoplasmic characteristics
      indicating normal germ cell differentiation. The principal cells of the cauda
      epididymis were characterized by the presence of well-de fi ned rough endoplasmic
      reticulum, mitochondria, Golgi bodies and secretary granules, suggesting active
      secretory functions. The absorptive function of the cauda epididymis was
      evidenced by the presence of numerous vesicles and multivesicular bodies adjacent
      to stereocilia. It is concluded that the inhibition of sperm motility by the drug
      could be due to other epididymal factors rather than the subcellular
      characteristics of testis and epididymis.

PMID- 15162363
TI  - Neuropharmacological profile of hydroalcohol extract of Valeriana edulis ssp.
      procera roots in mice.
AB  - Valerian is the common name given to the crude drug consisting of the underground
      organs of the species Valeriana. Valeriana edulis ssp. procera Meyer is the
      Mexican valerian. The aim of the present work was to elucidate the
      neuropharmacological profile of a hydroalcohol extract of Valeriana edulis roots
      at doses of 100, 300 and 1000 mg/kg in several experimental models. A dose
      dependent anticonvulsant and anxiolytic-like effect of V. edulis was
      demonstrated. In addition, the extract decreased rotarod performance and traction
      force and prolonged the pentobarbital-induced sleeping time at high doses.
      Concomitant administration of valerian extract and pentobarbital showed a
      synergistic effect on motor coordination and traction force in mice. The
      anxiolytic-like effect of V. edulis was compared with diazepam and with
      diphenhydramine and doxylamine, the latter in order to consider the H(1)
      antihistamine effect as another possibility to explain, at least in part, the
      central nervous system depressant effect of valerian. These results also underlie
      the medical and industrial use of this species and allowed the conclusion that
      the extract of V. edulis has central nervous depressant properties similar to,
      but with some differences to V. of ficinalis, a very well known species.

PMID- 15162364
TI  - Kava treatment in patients with anxiety.
AB  - In several clinical trials, mainly conducted with a dose of 300 mg kava extract
      per day, kava has been employed successfully for the treatment of anxiety
      disorders. The goal of the placebo-controlled double-blind outpatient trial was
      to obtain more information on the dosage range and efficacy of a kava special
      extract WS 1490 in patients with non-psychotic anxiety. 50 patients were treated
      with a daily dose of 3 x 50 mg WS 1490 during a 4-week treatment period followed
      by a 2-week safety observation phase. In the active treatment group, the total
      score of the Hamilton anxiety scale (primary efficacy variable), showed a
      therapeutically relevant reduction in anxiety versus placebo (more than 4
      points). In the secondary variables studied, HAMA 'somatic and psychic anxiety'
      subscales, the Erlangen anxiety, tension and aggression scale (EAAS), the brief
      personality structure scale (KEPS), the adjective checklist (EWL 60-S) and
      clinical global impressions scale (CGI), a trend in favour of the active
      treatment was detectable. WS 1490 was well tolerated and showed a safety profile
      with no drug-related adverse events or post-study withdrawal symptoms. It can be
      concluded that the applied 150 mg WS 1490 per day is an effective and safe
      treatment of non-psychotic anxiety syndromes in the described population.

PMID- 15162365
TI  - Effects of betaine, coumarin and flavonoids on mucin release from cultured
      hamster tracheal surface epithelial cells.
AB  - Betaine, coumarin, hesperidin and kaempferol are the components derived from
      Lycium chinense, Angelicae decursiva, Poncirus trifoliata and Polygonatum
      odoratum, respectively. These plants have been used for the treatment of
      respiratory diseases in oriental medicine and their respective components were
      reported to have various biological effects. In this study, we investigated
      whether these natural products affect mucin release from cultured hamster
      tracheal surface epithelial cells and compared the possible activities of these
      agents with the inhibitory action on mucin release by poly-L-lysine and the
      stimulatory action by adenosine triphosphate. Confluent primary hamster tracheal
      surface epithelial cells were metabolically radiolabeled using (3)H-glucosamine
      for 24 h and treated for 30 min in the presence of varying concentrations of each
      agent to assess the effects on (3)H-mucin release. The results were as follows:
      (i) Coumarin and kaempferol did not affect mucin release significantly; (ii)
      Betaine and hesperidin increased mucin release at the highest concentration;
      (iii) Poly-L-lysine inhibited and adenosine triphosphate increased mucin release.
      We conclude that betaine and hesperidin can increase mucin release by direct
      acting on airway mucin-secreting cells and suggest these agents be further
      studied for the possible use as mild expectorants during the treatment of chronic
      airway diseases.

PMID- 15162367
TI  - Ferulic acid alleviates lipid peroxidation in diabetic rats.
AB  - Diabetes mellitus is a metabolic disorder associated with increased formation of
      free radicals. The objective of our study was to determine whether ferulic acid
      (FA), a phenolic acid, has any role to play in diabetes induced free radical
      formation. Diabetes was induced with streptozotocin. The levels of blood glucose,
      thiobarbituric acid reactive substances (TBARS), hydroperoxides and free fatty
      acids (FFA) increased in the liver of diabetic animals. The activities of
      glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT)
      decreased in the liver. Histopathology of pancreas also shows shrunken islets.
      Supplementation of FA to the diabetic rats resulted in a decrease in the levels
      of glucose, TBARS, hydroperoxides, FFA and an increase in reduced glutathione
      (GSH). FA also resulted in increased activities of SOD, CAT, GPx and expansion of
      pancreatic islets. The effect was much pronounced with lower dose treatment. Thus
      our study shows that administration of ferulic acid helps in enhancing the
      antioxidant capacity of these diabetic animals by neutralizing the free radicals
      formed thereby reducing the intensity of diabetes.

PMID- 15162366
TI  - Tetrandrine induces apoptosis in hepatic stellate cells.
AB  - We have previously reported that tetrandrine reduced hepatic stellate cell
      activation and collagen accumulation in liver fibrosis induced by biliary
      obstruction. In the present study, we examined the apoptosis-inducing effect of
      tetrandrine on activated hepatic stellate cells, as the therapeutic goal in
      hepatic fibrosis is to eliminate the activated hepatic stellate cells by
      apoptosis. We used rat hepatic stellate cells transformed by Simian virus 40 (T
      HSC/Cl-6) to overcome the limitations inherent in studying primary cultures of
      hepatic stellate cells. Tetrandrine treatment at doses of 25 and 50 microg/ml for
      12 h induced apoptosis as confirmed by DNA fragmentation and increased sub-G1 DNA
      content as detected by flow cytometric analysis. Tetrandrine also induced the
      activation of caspase-3 protease and subsequent proteolytic cleavage of poly(ADP
      ribose) polymerase. In conclusion, our results demonstrate that tetrandrine
      induces apoptosis of T-HSC/Cl-6 cells, and these results should contribute to the
      development of new agents for the treatment of hepatic fibrosis.

PMID- 15162369
TI  - Protective effect of water yam (Dioscorea alata L.) extract on the copper-driven
      fenton reaction and X-ray induced DNA damage in vitro.
AB  - The rhizome extract of Dioscorea has been shown to possess radical scavenging
      activity. In this study, the protective effect of water yam (Dioscorea alata L.)
      rhizome extract on calf thymus DNA and plasmid DNA strand breakage by the copper
      driven Fenton reaction and X-irradiation was examined. The protective activity in
      vitro of four lyophilized extracts obtained from yam rhizomes: (1) aqueous
      extract (YAE); (2) 30% ethanolic extract (YEE); (3) aqueous extract boiled for 30
      min (BYAE); and (4) 30% ethanolic extract boiled for 30 min (BYEE) were evaluated
      by ethidium bromide binding assay and DNA nicking assay. The YAE, YEE, and BYEE
      effectively inhibited the copper-driven Fenton reaction-induced damage of calf
      thymus DNA, while inhibition was less pronounced in the case of X-ray induced
      strand breakage of plasmid DNA. While BYAE potently inhibited X-ray induced
      strand breaks in plasmid pGL3 DNA, it failed to inhibit, and even greatly
      enhanced copper-H(2)O(2) induced damage of calf thymus DNA. The present results
      demonstrate strong copper chelating and weak hydroxyl radical scavenging
      activities in yam rhizome extracts, and these activities may vary depending on
      the procedures used in preparing the extract.

PMID- 15162370
TI  - Hepatoprotective effect of Sabina przewalskii against menadione-induced toxicity.
AB  - Sabina przewalskii is a Tibetan medicinal plant. Pretreatment with an ethyl
      acetate-soluble fraction of the plant suppressed the plasma alanine
      aminotransferase activity in menadione-intoxicated mice. In vitro studies showed
      that the Sabina extract could inhibit NADH-induced superoxide production in
      isolated hepatocytes as indicated by a decrease of lucigenin-amplified
      chemiluminescence. In addition, the extract inhibited tert-butyl hydroperoxide
      induced lipid peroxidation in isolated hepatocytes dose-dependently. These
      results suggested that the protective action of the Sabina extract against
      menadione-induced hepatotoxicity is associated with its antioxidant activities
      including the scavenging of superoxide anion radicals and inhibition of lipid
      peroxidation.

PMID- 15162371
TI  - Trypanocidal activity of chemical constituents from Lychnophora salicifolia Mart.
AB  - The ethyl acetate extract from leaves plus inflorescences of L. salicifolia
      showed significant trypanocidal activity against trypomastigote forms of T.
      cruzi, which was due to the flavonoid quercetin-7,3',4'-trimethyl ether and the
      sesquiterpenoid lychnopholic acid. Despite the use of some species of Lychnophora
      in folk medicine for pain relief, crude extracts from L. salicifolia Mart. showed
      no antinociceptive activity in the mouse writhing test.

PMID- 15162372
TI  - Effect of Solenostemma argel on oviposition, egg hatchability and viability of
      Culex pipiens L. larvae.
AB  - Methanolic extracts of aerial parts of the medicinal plant Argel (Solenostemma
      argel (Del.) Hayne), incorporated into rearing media of Culex pipiens L. showed
      effect on oviposition, egg hatchability and larval viability. Acute toxicity of
      S. argel extract was found to possess LC(50) of 0.037, 0.031, 0.009 and 0.007 ppm
      and the LC(95) was found 0.394, 0.293, 0.065 and 0.030 ppm, after 1, 2, 4 and 7
      days against the larva of C. pipiens under laboratory conditions. The ovicidal
      effect of S. argel was relatively less pronounced, however, the 0.1%
      concentration reduced egg hatch by 33.7%. The mortality of the newly hatched
      larvae, reared from eggs in this media, reached 100% at concentrations as low as
      0.025%, 2 days post hatching. Complete suppression of oviposition within the
      first 2 days was observed, however its action was gradually lost thereafter.
      Bioactive effects were mainly attributed to the presence of a variety of
      bioactive organic substances mainly terpenes, pergenine glucosides, alkaloids and
      sterols.

PMID- 15162368
TI  - Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of
      Salvia species and their constituents.
AB  - Extracts of Salvia (sage) species have been reported to have cholinergic
      activities relevant to the treatment of Alzheimer's disease. A lack of
      information on the inhibition of the enzyme butyrylcholinesterase, also
      considered to be a target in the treatment of the disease, prompted this in vitro
      investigation of the essential oils of S. fruticosa, S. lavandulaefolia, S. of
      ficinalis and S. of ficinalis var. purpurea for anti-butyrylcholinesterase
      activity. Dose-dependent inhibition of human cholinesterases by the extracts and
      constituents was determined using the method of Ellman. A time dependent increase
      in the inhibition of butyrylcholinesterase by the oils of S. fruticosa and S. of
      ficinalis var. purpurea was evident. IC(50) values decreased from 0.15 +/- 0.007
      and 0.14 +/- 0.007 mg/mL after 5 min to 0.035 +/- 0.016 and 0.06 +/- 0.018 mg/mL
      after 90 min incubation time respectively. The slow onset of inhibition of
      butyrylcholinesterase was also shown by individual constituents, such as 3-carene
      and beta-pinene. Analyses of the chemical composition of the oils and anti
      butyrylcholinesterase activity of their constituents revealed that none of the
      compounds tested would account for the total activity of the oils and that
      synergy is likely.

PMID- 15162373
TI  - The antimicrobial activity of essential oils of Hypericum scabrum, Hypericum
      scabroides and Hypericum triquetrifolium.
AB  - The essential oils of Hypericum scabrum, Hypericum scabroides and Hypericum
      triquetrifolium were studied for the first time for their antimicrobial activity
      against nine organisms. All the essential oils exhibited some broad spectrum
      antibacterial activity, at a concentration of 80 microg/mL. The essential oils of
      Hypericum species showed antibacterial activity against the tested organisms and
      a yeast.

PMID- 15162375
TI  - Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft:
      association with tumor cell proliferation prior to recurrence.
AB  - BACKGROUND: Neuroendocrine (NE) cell differentiation is proposed to facilitate
      prostate cancer (CaP) recurrence following androgen deprivation through secretion
      by NE cells of growth factors and neuropeptides that support survival and
      proliferation of CaP cells and vasculature. METHODS: The effect of androgen
      deprivation on NE differentiation and tumor cell proliferation in the CWR22 model
      of human CaP was determined by immunohistochemical analysis of the NE cell marker
      synaptophysin and the cell proliferation marker Ki67. RESULTS: A significant
      increase in the number of NE cells was observed in CWR22 tumors between 28 and 66
      days after castration compared to intact mice, that preceded the increase in
      tumor cell proliferation that began 70 days after androgen deprivation heralding
      recurrence. There was a significant positive correlation between the number of
      tumor-associated NE cells and proliferating CaP cells in tumors from mice after
      28-34 days of androgen withdrawal. CONCLUSION: In the CWR22 model, androgen
      deprivation induces an increase in tumor-associated NE cells prior to increased
      tumor cell proliferation, with NE cells possibly promoting tumor survival and
      recurrent disease.

PMID- 15162374
TI  - Evidence of pluripotent human prostate stem cells in a human prostate primary
      xenograft model.
AB  - INTRODUCTION: The phenotypic plasticity of the human prostate stem cell within
      human prostate tissue was examined to determine the response of the stem cell to
      changes in the androgenic environment. METHODS: Prostate xenografts were
      transplanted into athymic nu/nu mice implanted with testosterone pellets, allowed
      to establish for 1 month time point, the hosts were castrated and pellets
      removed, and following 1 month of androgen deprivation, the hosts were stimulated
      with androgen for 2 days to induce proliferation of the residual population of
      stem cells (2-month time point). RESULTS: Glands in benign xenografts harvested
      at the 1- and 2-month time points contained basal cell layers that expressed p63
      and high molecular weight cytokeratin, and in which essentially all of the
      cellular proliferation was localized, consistent with the proposed localization
      of the prostate stem cell. Benign glandular structures in the xenografts were
      populated by basal, secretory epithelial, neuroendocrine (NE), or squamous cells
      overlaying the basal cell layer, whereas, adenocarcinoma glands in the xenografts
      resembled the original prostate cancer (CaP) tissue. CONCLUSIONS: In this human
      prostate primary xenograft model, the residual stem cell population that survives
      transplantation, or androgen deprivation, maintains significant pluripotentiality
      as demonstrated by the capacity to generate progeny that differentiate along
      multiple lineages in response to microenvironmental signals, particularly along
      the secretory epithelial lineage in response to androgen, and along the NE cell
      lineage in response to androgen deprivation.

PMID- 15162376
TI  - Lineage relationship between LNCaP and LNCaP-derived prostate cancer cell lines.
AB  - BACKGROUND: LNCaP and its derivative cell lines, which include C4-2 (and the
      related C4-2B) and CL1, are used as models of prostate cancer. Unlike LNCaP, the
      other cell lines show features of progressed disease such as metastatic
      capability and hormone independence. Analyses were done to determine if C4-2 or
      CL1 cells were selected from pre-existent subpopulations in LNCaP. METHODS:
      Prostate cancer cells were characterized by cluster designation (CD) phenotyping.
      Specific cell populations were sorted by flow cytometry. DNA array analysis was
      used to probe differential gene expression. RESULTS: CD phenotyping showed that
      CL1 and C4-2 (and C4-2B) were very dissimilar, and C4-2 was more similar to
      LNCaP. One common difference between LNCaP and its derivatives was CD26, in which
      virtually all C4-2 or CL1 cells were CD26(+) but only approximately 10% of LNCaP
      cells were CD26(+). The CD26(+) subpopulation of LNCaP was isolated and cultured
      in vitro. After culture, a high percentage of the cells (descended from the
      sorted cells) were CD26(+), in contrast to those sorted by CD13 or CD44. The
      cultured CD13 and CD44 populations did not show a high percentage of CD13(+) and
      CD44(+) cells, respectively. CD13 and CD44 are markers, in addition to CD26, for
      CL1 but not for C4-2. CONCLUSIONS: C4-2 arose probably from CD26(+) LNCaP cells,
      while CL1 arose de novo.

PMID- 15162378
TI  - Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in
      prostatic cancer cells.
AB  - BACKGROUND: Interleukin (IL)-6-mediated anti-apoptotic effects and drug
      resistance mechanisms in prostate cancer cells were investigated. METHODS: IL-6
      levels of PC-3 and LNCaP cells were studied by using ELISA. Protective effects of
      IL-6 on cytotoxic agent-induced apoptosis were studied by exogenous IL-6 in serum
      starved PC-3 cells and by anti-sense IL-6 strategy. Western blotting and reverse
      transcription-polymerase chain reaction (RT-PCR) were used to determine IL-6
      effects on Bcl-2 family proteins. Tetracycline-regulated Bcl-xL expression system
      and dominant negative STAT3 transfectants were used to study IL-6 signaling
      pathways and its anti-apoptosis effects. RESULTS: Exogenous IL-6 and anti-sense
      IL-6 oligonucleotide treatment conferred resistance to cytotoxic agent-induced
      apoptosis. Among Bcl-2 family proteins, only Bcl-xL was evidently increased by IL
      6 stimulation. The anti-apoptotic effect of IL-6 can be significantly attenuated
      by anti-sense bcl-xL transfection and partially abrogated in dominant negative
      STAT3 transfectants. CONCLUSIONS: IL-6 is a survival factor against cytotoxic
      agent-induced apoptosis through both STAT3 and bcl-xL pathways in prostate cancer
      cells.

PMID- 15162377
TI  - Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial
      neoplasia.
AB  - BACKGROUND: Evidence is accumulating that several proteases are involved in
      prostate cancer progression. A locus which is often amplified in prostate cancer
      is the chromosomal region 20q13. Interestingly, one of the genes encoding the
      cysteine protease cathepsin X maps to this region. The aim of this study was to
      assess the expression pattern of cathepsin X in malignant and non-malignant
      prostatic tissue samples. METHODS: Matched malignant and non-malignant tissue
      specimens were obtained from 56 men after radical prostatectomy. Cathepsin X was
      quantified at both protein and mRNA levels using several detection methods:
      Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ
      hybridization. Furthermore, genomic DNA was analyzed by PCR for possible gene
      amplification. RESULTS: Immunohistochemical analysis of formalin-fixed, paraffin
      embedded sections of radical prostatectomy specimens was performed utilizing a
      polyclonal antibody against human procathepsin X and revealed staining of acinar
      basal cells in normal prostate glands. Prostatic intraepithelial neoplasias
      (PINs) and prostate carcinomas stained highly positive for cathepsin X, showing a
      significant difference to the staining of normal prostate glands. In contrast,
      relatively weak and heterogeneous staining was observed for cathepsins F, B, and
      L. Up-regulation of cathepsin X at the protein level was confirmed by Western
      blotting. No statistically significant difference was observed at the mRNA level.
      PCR of genomic DNA revealed that cathepsin X up-regulation most likely occurs in
      the absence of genomic amplification. CONCLUSIONS: The high expression levels of
      cathepsin X both in PIN and invasive adenocarcinomas of the prostate suggest that
      cathepsin X may play a role in the early tumorigenesis of prostate cancer.
      Further studies are needed to define the utility of this cysteine protease as a
      diagnostic marker for the early detection of prostate cancer.

PMID- 15162379
TI  - Translationally controlled tumor protein (TCTP) in the human prostate and
      prostate cancer cells: expression, distribution, and calcium binding activity.
AB  - BACKGROUND: The translationally controlled tumor protein (TCTP) is an abundantly
      expressed protein found in a wide range of organisms from both the animal and
      plant kingdom. Initially described as a growth-related protein, knowledge of the
      biological actions of TCTP has been recently extended to include calcium binding,
      regulation of apoptosis, and microtubules stabilization. This report describes
      expression, distribution, and characterization of TCTP in human prostatic tissues
      and cell lines. METHODS: Samples were analyzed by Western blot, RT-PCR,
      immunohistochemistry, and confocal microscopy. Calcium binding activity of the
      recombinant human prostatic protein was evaluated on a calcium overlay assay. A
      public SAGE database was analyzed to determine TCTP expression levels in normal
      and cancer tissues. RESULTS: TCTP protein and mRNA were detected in all the
      specimens and cell lines analyzed. The protein was mainly expressed by the
      secretory luminal epithelial and basal layer cells. A significant amount of
      protein was present in the prostatic fluids. Subcellular distribution studies in
      prostate epithelial cells detected the protein in the cytoplasm in interphase and
      colocalized with tubulin during mitosis. The calcium binding capacity of
      prostatic TCTP was shown in vitro. Finally, SAGE data indicated TCTP as the
      calcium binding protein with the highest expression levels among those examined.
      CONCLUSIONS: The results of the present study demonstrate, for the first time,
      the expression of TCTP in the human prostate and in prostate cancer cells, and
      suggest the involvement of the protein in key-processes such as apoptosis,
      cellular differentiation, and in the control of sperm functions.

PMID- 15162380
TI  - Establishment and characterization of a primary androgen-responsive African
      American prostate cancer cell line, E006AA.
AB  - BACKGROUND: Establishment of human prostate cancer cell lines is essential to
      advance our understanding of complex processes associated with the initiation and
      progression of the disease. In the present study, we report the establishment of
      a primary African-American prostate cancer cell line (E006AA) as well as its
      associated stromal cells (S006AA). METHODS: E006AA cell line was established as a
      spontaneously immortalized cells from a patient with a clinically localized
      prostate cancer. Extensive characterization of the cells was accomplished using
      androgen-dependent growth and sensitivity assays, Western analyses, RT-PCR/real
      time PCR, cytogenetic analyses, and tumorigenicity in nude mice. RESULTS: E006AA
      cell line shows androgen-dependent growth, expresses PSA and the androgen
      receptor (AR) with 26 CAG repeats in exon 1 of AR. Cytogenetic analyses revealed
      a hypertriploid karyotype with additional numerical gains in chromosomes 5, 6, 8,
      10, 17, 20, 21 and a marker chromosome of unknown origin as well as structural
      abnormalities in chromosomes 4, 5, 8, 9, 11-14, 18, and 20. This cell line is not
      tumorigenic in nude mice. S006AA cell line, isolated from the same tumor
      specimen, also expresses AR and shows the morphological characteristics of smooth
      muscle cells of prostatic stroma. CONCLUSIONS: These cell lines are the first
      available primary epithelial and stromal cells derived from an African-American
      patient with organ-confined prostate cancer and in conjunction with other
      established cell lines, could provide an in vitro model system to investigate
      early transforming events in prostate cancer.

PMID- 15162381
TI  - Interleukin-8 expression is increased in senescent prostatic epithelial cells and
      promotes the development of benign prostatic hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is an extremely common disease of
      older men characterized by increased growth of prostatic epithelial and stromal
      cells. Previously we showed that senescent epithelial cells accumulate in the
      prostate of aging men and secrete interleukin-1 alpha (IL-1 alpha). IL-8 is also
      present at increased levels in BPH tissues and induces expression of FGF2, a
      potent stromal growth factor. Therefore, we sought to determine if IL-8 is also
      expressed at increased levels by senescent epithelial cells and if this secreted
      IL-8 plays a role in the pathogenesis of BPH. METHODS: Expression of IL-8 in
      human BPH tissue and primary cultures of prostatic epithelial cells was analyzed
      using an enzyme-linked immunoabsorption assay (ELISA). Tissue senescence was
      assessed by a quantitative assay for senescence-associated beta galactosidase (SA
      beta gal). Proliferation of primary and immortalized prostatic epithelial cells
      in response to IL-8 was determined by counting of cells at intervals after
      addition of IL-8. RESULTS: Expression of IL-8 is significantly increased in vitro
      when cultured prostatic epithelial cells undergo senescence. Quantitative assay
      of BPH tissue extracts revealed that tissue IL-8 levels are correlated with both
      SA-beta gal activity and prostate weight. IL-8 promotes proliferation of primary
      and immortalized prostatic epithelial cells in culture. CONCLUSIONS: Senescence
      of prostatic epithelial cells results in increased expression of IL-8, which can
      promote proliferation of non-senescent epithelial and stromal cells by direct and
      indirect mechanisms, and in this manner contributes to the increased tissue
      growth seen in BPH.

PMID- 15162382
TI  - High mobility group protein HMGI(Y) enhances tumor cell growth, invasion, and
      matrix metalloproteinase-2 expression in prostate cancer cells.
AB  - BACKGROUND: The high mobility group protein HMGI(Y) has oncogenic properties and
      correlates with an aggressive phenotype in prostate cancer. The molecular
      mechanisms involved in transformation associated with HMGI(Y) overexpression
      remain unknown. METHODS: The HMG-I isoform was transfected and overexpressed in
      nonmetastatic Dunning prostate cancer cells (G cells) without detectable HMGI(Y).
      The assays of cell proliferation, tumor formation, in vitro invasion, and cDNA
      microarray were performed to assess the effect of HMGI(Y) overexpression in the
      transfected G cells. RESULTS: Overexpression of HMG-I in G cells significantly
      increases cell proliferation and tumor growth and also modestly enhances in vitro
      invasion compared to mock transfectant. cDNA microarray revealed that expression
      of the matrix metalloproteinase-2 (MMP-2) proform was increased eightfold in G
      cells overexpressing HMG-I. CONCLUSIONS: Overexpression of HMG-I in prostate
      cancer cells enhances cell growth, invasion, and expression of the proform of MMP
      2, which may initiate early steps involved in the metastatic cascade.

PMID- 15162384
TI  - Evaluation of experimental strategies for the development of chiral
      chromatographic methods based on diastereomer formation.
AB  - The past two decades has seen explosive growth in the field of chirality as
      illustrated by the rapid progress in the various facets of this intriguing field.
      Firstly, it is the basic understanding of the importance of chirality and,
      secondly, the awareness of the therapeutic pitfalls due to failure to recognize
      chirality that have paved the way for a rejuvenated interest in the field.
      Needless to say that the impetus for chiral separation advancement and
      enhancement has been found to be the highest in the past decade and still
      continues to be an area of high focus. In this regard, both direct and indirect
      separation approaches have been instrumental in placing into literature
      stereoselective pharmacokinetic and pharmacodynamic data of plethora of drug
      racemates. Also, today, the cloud of uncertainty associated with the development
      of a chiral molecule is a thing of the past because the field is so evolved and
      numerous options are available for stereoselective analysis. However, the
      decision to advance either a single enantiomer or a racemate for development has
      to be made by a rational approach with adequate justification. Although indirect
      method of chiral separation has been well established with numerous examples of
      well-documented cases of stereoselective pharmacokinetic data, there is a growing
      need for a review that provides a strategic overview of considerations and key
      issues for developing chromatographic methods based on diastereomer formation.
      This review provides a general framework for the exploratory planning and a
      definitive game plan for the establishment of chiral methods based on
      diastereomer formation. Also, it provides an exhaustive list of applications of
      numerous chiral derivatization reagents that have been used in the generation of
      stereoselective pharmacokinetic data.

PMID- 15162383
TI  - Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via
      activation of protease-activated receptors.
AB  - BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic
      enzymes involved in facilitating cancer metastasis. Protease-activated receptors
      (PARs) have previously been shown to be involved in pathways of MMP upregulation
      by tumor cells. METHODS: Two androgen independent prostate cancer cell lines, PC3
      and DU-145, and one androgen dependent prostate cancer line LNCaP, were
      investigated. PAR expression was detected using RT-PCR and immunofluorochemistry
      (IFC) techniques. MMP activity assays were used to quantify the levels of MMP-2
      and -9 on all three prostate cell lines after PAR activation. RESULTS: RT-PCR and
      IFC showed the presence of PAR-1 and PAR-2 in all cell lines investigated, only
      LNCaP showed PAR-3 and PAR-4 expression. Increased levels of MMP-2 and MMP-9
      activity, up to sevenfold depending on prostate cancer cell line, following PAR
      activation by specific PAR peptides was shown. CONCLUSION: Preliminary studies
      show the activation of PAR-1 or PAR-2 produced increased levels of MMP-2 and MMP
      9 activity in prostate cancer cell lines, indicating their potential role in the
      metastasis of prostate cancer cells.

PMID- 15162386
TI  - Encapsulation of isohexenylnaphthazarins in cyclodextrins.
AB  - Naturally occurring isohexenylnaphthazarins (IHN), such as Alkannin, Shikonin
      (A/S) and their derivatives, are potent pharmaceutical substances with a wide
      spectrum of biological activity. In the present study, inclusion complexes of
      alkannin and shikonin commercial samples and IHN derivatives in the form of an
      oily extract of Alkanna tinctoria roots were formed with beta-cyclodextrin (CD)
      and beta-HPCD. These complexes were investigated to evaluate the effect of
      complexation on their aqueous solubility, decoloration, and also the percentage
      of polymeric A/S and IHN derivatives enclosed in the CDs cavity, since these
      decrease the active monomeric IHN. Both beta-CD and beta-HPCD increased the
      aqueous solubility of A/S and IHN derivatives and thus inclusion complexes can be
      used as drug delivery systems for A/S in both internal (capsules, tablets) and
      external hydrophilic pharmaceutical and cosmetic preparations (creams, gels,
      sprays) with enhanced bioavailability. The inclusion complexes formed had a pale
      purple colour, contributing to the partial decoloration of the A/S and thus of
      the fi nal pharmaceutical preparations. Finally, CDs selectively included more
      monomeric and less polymeric IHN, compared with the initial each time sample that
      is encapsulated; thus inclusion complexes may present enhanced biological
      activity.

PMID- 15162385
TI  - One-step analysis of testis steroidogenesis from neonatal exposure to synthetic
      estrogen by normal-phase HPLC.
AB  - Neonatal exposure to synthetic estrogen endocrine disruptors or estrogen-receptor
      inhibitors induces developmental abnormalities in the male reproductive system.
      To investigate whether neonatal exposure affects spermatogenesis in juvenile and
      pubertal testis, Sprague-Dawley rat pups were given synthetic estrogen endocrine
      disruptors or estrogen-receptor inhibitors by a single injection on the day of
      birth at concentrations ranging between 2 to 40 mm, and sacrificed on day 21
      (juvenile), 35 (prepuberty) or 50 (puberty). The testes were weighed and examined
      histologically at each stage. Further, the metabolites of steroidogenesis were
      analyzed using normal-phase high performance liquid chromatography. Neonatal
      exposure significantly reduced testis weights and steroidogenesis to one- fifth
      to one-half of that of the juvenile control, and further suppressed irreversible
      steroidogenesis and spermatogenesis during puberty.

PMID- 15162387
TI  - Simultaneous determination of chlorpheniramine and pseudoephedrine in human
      plasma by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and specific procedure for simultaneous quantitation of
      chlorpheniramine and pseudoephedrine in human plasma has been developed and
      validated. Analytes were extracted from plasma samples by liquid-liquid
      extraction, separated on a Diamonsil C18 column (250 x 4.6 mm i.d.) and detected
      by tandem mass spectrometry with an atmospheric pressure chemical ionization
      interface. Diphenhydramine was used as the internal standard. The method has a
      lower limit of quantitation of 0.2 and 2.0 ng/mL for chlorpheniramine and
      pseudoephedrine, respectively. The intra- and inter-day relative standard
      deviation, calculated from quality control (QC) samples were below 4.3% for
      chlorpheniramine and below 9.5% for pseudoephedrine. The inter-day relative error
      as determined from QC samples was within 4.7% for each analyte. The overall
      extraction recoveries of chlorpheniramine and pseudoephedrine were 77 and 61% on
      average, respectively. The method was successfully applied to pharmaockinetic
      study of chlorpheniramine and pseudoephedrine in volunteers receiving
      formulations containing 4 mg of chlorpheniramine maleate and 60 mg of
      pseudoephedrine hydrochloride.

PMID- 15162389
TI  - The Hummel-Dreyer method: impact in pharmacology.
AB  - Reviews devoted to drug-protein binding present mostly a variety of analytical
      methods applied to studying the unique process when the protein reversibly binds
      a low-molecular-weight substance-the drug. This report, however, reviews the
      great majority of papers presenting the application of one particular method
      introduced by Hummel and Dreyer in 1962: Measurement of protein-binding phenomena
      by gel filtration. The main criterion in reviewing published papers was the
      application of the Hummel-Dreyer method when the counterpart substances were the
      drug and the human plasma protein.

PMID- 15162388
TI  - A validated HPLC method with ultraviolet detection for the determination of
      buformin in plasma.
AB  - A sensitive and rapid high-performance liquid chromatographic assay is developed
      and validated for the determination of buformin in plasma. After addition of
      metformin as the internal standard, the analytes were deproteinated with
      acetonitrile, washed with dichloromethane, and the resulting supernatant
      injected. Chromatography was performed at ambient temperature by pumping a mobile
      phase of 0.03 m diammonium hydrogen phosphate buffer (pH 7, 250 mL) in methanol
      (750 mL) at a fl ow rate of 1 mL/min through a silica column. Buformin and
      metformin were detected at 236 nm, and eluted 9.8 and 15.4 min, respectively. No
      endogenous substances were found to interfere. Calibration curves were linear
      over the concentration range of 20-2000 ng/mL. The limit of quantitation was 20
      ng/mL. The intra- and inter-day relative standard deviation (RSD) was 8.3%, or
      less, and the accuracy was within 10.1% of the relative error (RE). The method is
      suitable in pharmacokinetic investigation of buformin.

PMID- 15162390
TI  - Role of peg formation in clamp cell fusion of homobasidiomycete fungi.
AB  - In most filamentous basidiomycetes, clamp cells are found at the septa of
      dikaryotic mycelia. Clamp cell formation starts at hyphal tip cells with the
      development of a lateral bulge at a position slightly apical to the future
      septum. Relative to the growth direction of the hypha, the protrusion expands
      backwards into a hook-like structure. Next, the two genetically different haploid
      nuclei within the hyphal tip cell divide. A septum appears between clamp cell and
      hyphal tip cell, thereby trapping one nucleus within the clamp cell. Another
      septum is laid within the hypha, separating a nucleus of the other type in the
      newly generated subapical hyphal cell from the two different nuclei kept together
      in the new apical hyphal cell. Through fusion of clamp and subapical cell, the
      two solitary nuclei become united within the subapical hyphal compartment. In
      1933, Buller described subapical formation of a peg to which the clamp cell fuses
      as an additional, subsequently neglected step in this series of events. In this
      study, we represent evidence for subapical peg formation and its role in clamp
      cell fusion. Our observations potentially indicate a B mating type regulated
      extracellular communication between clamp and subapical hyphal cell.

PMID- 15162391
TI  - Effects of hydrogen peroxide on light emission by various strains of marine
      luminescent bacteria.
AB  - Light-emitting bacteria are the most abundant and widespread luminescent
      organisms. Most species of such bacteria live in marine environments. However,
      until recently, biological role of bacterial luminescence remained unknown.
      Recent studies indicated that light produced in bacterial cells may stimulate DNA
      repair. Therefore, it is not surprising that agents that cause DNA damage induce
      expression of lux genes. Moreover, it was proposed previously that bacterial
      luciferases may be involved in detoxification of reactive oxygen species.
      Recently, this hypothesis was confirmed experimentally. Here we investigated
      effects of hydrogen peroxide on light emission by various strains of luminescent
      bacteria. We found that luminescence of strains with luciferase of fast kinetics
      of reaction decreased at considerably lower concentrations of H2O2 than that of
      strains with luciferase of the slow kinetics. The action (either direct or
      indirect) of luciferases as anti-oxidants seemed to be independent of activity of
      catalase, which was found to be different in various strains. Therefore, it seems
      that luciferases of the slow kinetics are more efficient in detoxification of
      reactive oxygen species than those of the fast kinetics.

PMID- 15162392
TI  - Cytosolic NADP phosphatases I and II from Arthrobacter sp. strain KM: implication
      in regulation of NAD+/NADP+ balance.
AB  - NADP phosphatase (NADPase) is an enzyme that converts NADP+ into NAD+ through
      dephosphorylation of NADP+, and is considered to be one of the possible
      candidates for regulation of the NAD+/NADP+ balance in vivo. In order to obtain
      an intrinsic NADPase, the NADP+-degrading activity in a membrane-free cell
      extract of a Gram-positive bacterium, Arthrobacter sp. strain KM, was first
      assessed and demonstrated to be mainly achieved through the NADPase reaction,
      indicating NADPase is essential for degradation of NADP+ and therefore for
      regulation of the NAD+/NADP+ balance in cytosol. Then, the isolation of cytosolic
      NADPase was attempted using NADP+ as a substrate. Two NADPase isozymes,
      designated as NADPases I and II, were purified from the cell extract of the
      bacterium, and were indicated to be the sole cytosolic NADPases regulating the
      balance of NAD+/NADP+. NADPases I and II are homodimers of 32 and 30 kDa
      subunits, respectively, and most active at pH 7-8. The N-terminal amino acid
      sequences of the two enzymes are similar to each other. Among the biological
      substrates tested, both enzymes showed the highest activity toward NADP+ and
      NADPH. AMP, ADP, and pyridoxal 5'-phosphate were also dephosphorylated, but to
      lower extents. Comparison of the features of NADPases I and II with those of
      other acid phosphatases possessing NADPase activity suggested that NADPases I and
      II are novel enzymes participating in regulation of the NAD+/NADP+ balance in the
      cytosol.

PMID- 15162393
TI  - Evaluation of three new culture media for the cultivation and isolation of
      Leishmania parasites.
AB  - The aim of this study was to establish novel culture media for Leishmania
      parasites with a potential of obtaining high amounts of promastigotes with long
      term viability, and consisting of ingredients that were available in microbiology
      or parasitology laboratories. Other features of these media included no
      requirement for blood, FCS (Fetal calf serum) or erythrocyte lysate,
      inexpensiveness and easiness in preparation. In addition, aspiration samples
      obtained from cutaneous leishmaniasis (CL) suspected patients were cultivated in
      these media. Three culture media were prepared; trypticase beef extract
      hemoglobine (TBH) medium, including trypticase, beef extract and yeast extract as
      the protein source, glucose as the carbohydrate source, FeNH4 and bovine
      hemoglobine; Peptone-Yeast extract medium (PY), found to be effective in our
      previous studies for cultuvation of on Leishmania parasites, with bovine
      hemoglobine (PYH) and Brain Heart medium, containing bovine hemoglobine (BKH).
      The number of promastigotes were the highest on day 8 and 13 in RPMI 1640 and BKH
      medium, respectively. In TBH and PYH, the peak level of reproduction was between
      day 16 and 19, and it was found to be higher in TBH medium after the day 20. The
      number of promastigotes were found to be close in BKH, TBH and RPMI-1640 media
      and lower in PYH medium. Examination of the cultivation of the aqueous lesion
      specimens of the 10 CL-suspected cases in media revealed reproduction in 9 flasks
      of RPMI-1640 containing 10% FCS, 7 TBH, 6 BKH and 4 PYH. The differences between
      the culture media were not found to be statistically significant. These results
      suggested that, three liquid culture media, assessed in this study, with no
      requirement for FCS or erythrocyte lysate, were effective in the reproduction of
      promastigotes, and could be used effectively in the patient isolation and field
      studies, as well.

PMID- 15162394
TI  - Searching for nitrile hydratase using the Consensus-Degenerate Hybrid
      Oligonucleotide Primers strategy.
AB  - Consensus-Degenerate Oligonucleotide Hybrid Primers (CODEHOP) were designed by
      using the WWW-implemented strategy, based on multiple alignments of nitrile
      hydratase (NHase) alpha subunit, available from EMBL database. These primers were
      successfully tested with known NHase-producing bacterial strains such as
      Agrobacterium tumefaciens DSM 9674, Rhodococcus erythropolis DSM 9675, R.
      erythropolis 9685 and R. erythropolis 11397 and also allowed amplification from
      organisms not previously referenced (Variovorax sp. DSM 11402 and Agrobacterium
      sp. DSM 11401). Hybrid primer utilisation was evaluated by analysing the
      incorporated sequences in cloned PCR fragments. Several primers from the
      oligonucleotide pool seemed to participate in the amplification of the correct
      fragment. Common garden soil was used as a source for both acetonitrile culture
      enrichment screening and direct DNA extraction. A R. erythropolis strain (CCMI
      1005) was isolated by culture enrichment and allowed the PCR amplification of a
      DNA sequence (AJ548493) identical to the NHase coding sequences commonly
      described for that species, while the direct use of soil DNA as template led to
      the CODEHOP detection of two putative NHase coding sequences (AJ548498 and
      AJ548499), which were significantly different from any other known sequence. The
      phylogenetic relationship between all sequences obtained and the published NHase
      coding sequences was assessed by neighbour-joining analysis. The results
      demonstrate the use of consensus-degenerate primers in NHase detection from
      organisms known to express it and in the screening for new NHase family members.

PMID- 15162395
TI  - Nucleotide sequence analysis of the recA gene and discrimination of the three
      isolates of urease-positive thermophilic Campylobacter (UPTC) isolated from
      seagulls (Larus spp.) in Northern Ireland.
AB  - Nucleotide sequencing after TA cloning of the amplicon of the almost-full length
      recA gene from three strains of UPTC (A1, A2, and A3) isolated from seagulls in
      Northern Ireland, the phenotypical and genotypical characteristics of which have
      been demonstrated to be indistinguishable, clarified nucleotide differences at
      three nucleotide positions among the three strains. In conclusion, the nucleotide
      sequences of the recA gene were found to discriminate among the three strains of
      UPTC, A1, A2, and A3, which are indistinguishable phenotypically and
      genotypically. Thus, the present study strongly suggests that nucleotide sequence
      data of the amplicon of a suitable gene or region could aid in discriminating
      among isolates of the UPTC group, which are indistinguishable phenotypically and
      genotypically.

PMID- 15162396
TI  - Production of lignocellulolytic enzymes by Trametes gallica and detection of
      polysaccharide hydrolase and laccase activities in polyacrylamide gels.
AB  - White rot fungus Trametes gallica was studied for the production of
      lignocellulolytic enzymes: cellulase, xylanase, laccase, manganese-dependent
      peroxidase (MnP), and lignin peroxidase (LiP). The results demonstrated that low
      nitrogen (2.2 mM N) and surface stationary cultivation favored production of
      extracellular MnP. MnP activity reached 118.1 UL(-1) while T. gallica was grown
      in a low-nitrogen culture containing phenylalanine. However, laccase levels
      observed in high-nitrogen (22 mM N) agitated cultures were much greater than
      those seen in low-nitrogen. The N source experiments seemed to reveal that NH4+
      plays an important role in inducing MnP and laccase of the fungus. Results showed
      that T. gallica produces a series of the lignocellulolytic enzymes, and needs
      high N to produce all the enzymes during solid-state fermentation of wheat straw.
      This paper also presents a modified zymogram procedure to detect xylanase and
      laccase of T. gallica in polyacrylamide gel. Xylanase in crude enzyme of T.
      gallica was displayed by contacting protein gel strips with xylan substrate gels
      and by staining with iodine. By immersing the protein gel strips in o-tolidine
      solution, the blue-green zones representing laccase activity were visualized
      against a colorless background.

PMID- 15162397
TI  - Major outer membrane proteins in moderately halophilic eubacteria of genera
      Chromohalobacter and Halomonas.
AB  - Outer and inner membrane fractions of Chromohalobacter marismortui and Halomonas
      elongata were isolated by differential detergent solubilization, and profiles of
      membrane proteins, especially major outer membrane proteins, were analyzed. These
      type strains possessed one extremely abundant outer membrane protein which showed
      similarity in amino-terminal amino acid sequence with the outer membrane porin
      proteins in other Gram-negative bacteria. Three halophilic eubacterial strains
      isolated from saline environments were also characterized. Strains 160 and 43
      were found to be Chromohalobacter spp. and strain 40 to be a Halomonas sp. by
      sequence analysis of their 16 S ribosomal RNA genes. Extremely abundant porin
      proteins with an apparent molecular mass of 49 kDa were found in Chromohalobacter
      sp.160 and Halomonas sp. 40, but no major outer membrane protein was detected in
      Chromohalobacter sp. 43, suggesting strain 43 was most likely a naturally
      defective porin mutant. Porin proteins from Chromohalobacter spp. and Halomonas
      spp. showed the same migration on SDS-polyacrylamide gel electrophoresis with or
      without heat-treatment, indicating that these porin proteins did not form a SDS
      resistant trimeric structure, which was detected in most of the Gram-negative
      bacterial porin proteins.

PMID- 15162398
TI  - Isolation, characterization and beneficial effects of rice associated plant
      growth promoting bacteria from Zanzibar soils.
AB  - This study was undertaken to isolate and characterize plant growth promoting
      bacteria (PGPB) occurring in four soils of Zanzibar, Tanzania as well as to
      evaluate their potential use as biofertilizers for rice. A total of 12 PGPB
      strains were isolated from rice and studied for growth characteristics,
      carbon/nitrogen source utilization patterns using QTS-24 kits, phosphate
      solubilization, indole acetic acid (IAA) production, antibiotic resistance
      patterns and growth at different pH, temperature and salt concentrations. All the
      isolates were motile and gram negative except Z3-4. Acetylene reduction activity
      was detected in all isolates ranging from 5.9-76.4 nmole C2H2 reduced/h x mg
      protein while 9 isolates produced IAA ranged from 20-90.8 mg/l. Most of the
      isolates showed resistance against different environmental stresses like 10-40
      degrees C temperature, 0.2-1 M salt concentration and 4-8.5 pH range. Only one
      isolate Z2-7 formed clear zones on Pikovskaia's medium showing its ability to
      solubilize phosphates. Z3-2 was used to develop fluorescent antibodies to check
      the cross reactivity of the isolates. Inoculation of these bacterial isolates
      resulted in higher plant biomass, root area, and total N and P contents on
      Tanzanian rice variety BKN PRAT3036B under controlled conditions. Bacillus sp. Z3
      4 and Azospirillum sp. Z3-1 are effective strains and, after further testing
      under field conditions, can be used for inoculum production of rice in Tanzania.
      The plant growth promoting effects of these PGPRs suggest that these can be
      exploited to improve crop productivity of rice in Tanzania.

PMID- 15162399
TI  - Control of pyrimidine biosynthesis in "Pseudomonas alkanolytica" ATCC 21034.
AB  - The control of de novo pyrimidine biosynthesis in the industrially important
      patent strain "Pseudomonas alkanolytica" ATCC 21034 was investigated. Uracil
      supplementation of succinate-grown "P. alkanolytica" cells produced the greatest
      depression of the de novo pyrimidine biosynthetic pathway enzyme activities.
      After the pyrimidine limitation of a "P. alkanolytica" orotate
      phosphoribosyltransferase mutant strain grown on succinate, the pyrimidine
      biosynthetic pathway enzyme activities were derepressed. The pyrimidine
      biosynthetic pathway enzyme aspartate transcarbamoylase in "P. alkanolytica" was
      inhibited by pyrophosphate, cytidine 5'-triphosphate (CTP), uridine 5'
      triphosphate (UTP), and guanosine 5'-triphosphate (GTP).

PMID- 15162400
TI  - Alpha2beta1 integrin-specific collagen-mimetic surfaces supporting osteoblastic
      differentiation.
AB  - The interactions of osteoblasts with their surrounding extracellular matrix (ECM)
      are essential for skeletal development, homeostasis, and maintenance of the
      mature osteoblastic phenotype. Integrins are the principal transducers of ECM
      signals that regulate this process of osteoblast commitment and differentiation.
      Several studies indicate that the alpha(2)beta(1) integrin interaction with type
      I collagen is a crucial signal for the induction of osteoblastic differentiation
      and matrix mineralization. Integrin alpha(2)beta(1) recognizes the Gly-Phe-Hyp
      Gly-Glu-Arg (GFOGER) motif in residues 502-507 of the alpha(1)[I] chain of type I
      collagen. This study demonstrates that an alpha(2)beta(1) integrin-specific
      GFOGER peptide triggers the activation of focal adhesion kinase and alkaline
      phosphatase in MC3T3-E1 murine immature osteoblast-like cells, two events that
      have been implicated in the osteoblastic differentiation pathway. These GFOGER
      peptide surfaces also support the expression of multiple osteoblast-specific
      genes, including osteocalcin and bone sialoprotein, and induce matrix
      mineralization in a manner similar to type I collagen. This triple-helical
      peptide represents a promising surface modification strategy for the design of
      collagen-mimetic bioadhesive surfaces that support osteoblastic differentiation.

PMID- 15162401
TI  - Mechanics considerations for microporous titanium as an orthopedic implant
      material.
AB  - This article investigates mechanics issues related to potential use of a recently
      developed porous titanium (Ti) material for load-bearing implants. This material
      may have advantages over solid Ti of enhancing the bone-implant interface
      strength by promoting bone and soft tissue ingrowth and of reducing the bone
      implant modulus mismatch, which can lead to stress shielding. Experimental data
      from ultrasound experiments and uniaxial compression testing on microporous Ti
      are presented. Analytic models to predict its elastic modulus and Poisson's ratio
      are discussed, including "structural" approaches (Gibson and Ashby's cellular
      solids) and a "composite material" approach (Mori-Tanaka). Finally, two
      dimensional finite element models based on optical micrographs of the material
      are presented. Simulations were performed for different conditions and levels of
      approximation. Results demonstrate that simple analytic models provide good
      estimates of the elastic properties of the porous Ti and that the moduli can be
      significantly reduced to decrease the mismatch between solid Ti and bone. The
      finite element simulations show that bone ingrowth will dramatically reduce
      stress concentrations around the pores.

PMID- 15162402
TI  - Biomaterial surface-dependent neutrophil mobility.
AB  - Compromised neutrophil function in the presence of an implanted biomaterial may
      represent an important mechanism that allows for the development of implant
      associated infections. Here, human neutrophil mobility has been investigated on a
      polyurethane (ChronoFlex AR), a hydrophobic surface consisting of an
      octadecyltrichlorosilane (OTS) self-assembled monolayer, and a glass reference
      material. Neutrophil mobility was quantified, based on cell movement speed and
      persistence time obtained from time-lapse optical microscopy, while neutrophil
      cytoskeletal structures and morphology were visualized using confocal microscopy
      and atomic force microscopy. Our results show that material surface properties
      affect neutrophil-surface interactions, as reflected by morphological changes,
      and the mobility of neutrophils stimulated by N-formylmethionyl-leucyl
      phenylalanine (fMLP). In the absence of adsorbed plasma proteins, the mobility of
      stimulated neutrophils increased with increasing material hydrophobicity from
      glass, to polyurethane, to OTS. The opposite trend was observed in the presence
      of adsorbed plasma proteins, such that neutrophil mobility increased with
      decreasing material hydrophobicity. Analysis of the results showed that the
      mobility of fMLP-stimulated neutrophils cells was inversely related to the extent
      of cell spreading on the materials.

PMID- 15162403
TI  - Osteoblast responses to tape-cast and sintered bioactive glass ceramics.
AB  - The advantage of tape-cast bioactive glasses lies in the manufacturing procedure,
      which allows the build-up of layers and, therefore, the production of complex
      shapes. This, therefore, has applications to tissue engineering, where specific
      shapes are required such as repair of craniofacial defects. The bioactivity of
      tape-cast discs sintered at temperatures ranging from 800 degrees C to 1000
      degrees C and for 3 or 6 h was analyzed by FTIR. Tape-cast discs were used to
      culture primary human osteoblasts, and cell attachment, cell death, collagen
      production, nodule formation, and mineralization were studied. These responses
      were dependent upon Si and Na release profiles of the tape-cast discs, and
      development of the hydroxyapatite layer.

PMID- 15162404
TI  - In vivo evaluation of a biomimetic apatite coating grown on titanium surfaces.
AB  - Osteoconductive mineral coatings represent an established technology for
      enhancing the integration of orthopedic implants with living bone. However,
      current coatings have limitations related to fabrication methods, attachment
      strength to metal substrates, and in vivo performance. Low temperature biomimetic
      growth is a coating technique wherein the device to be coated is immersed in a
      meta-stable saturated solution of the coating constituents and growth of the
      coating is then allowed to proceed on the surface of the device. This study
      focused on the in vivo evaluation of a biomimetic apatite coating fabricated
      under these conditions. The experiment was designed to specifically test the
      amount of bone ingrowth into the coated channels versus the uncoated channels of
      an established bone chamber system, with emphasis placed on the amount of bone
      present on the coupon surface. Three types of measurements were taken on each
      channel: linear ingrowth %, area ingrowth %, and continuous bone apposition %.
      The experiments demonstrated that under controlled conditions, the apatite
      coating appears to resorb in 8 weeks and did stimulate early osseointegration
      with the metal surface with a reduction in fibrous tissue encapsulation. This
      coating may, therefore, be useful in facilitating early bone ingrowth into porous
      surfaces without the potential for coating debris, macrophage infiltration,
      fibrous tissue encapsulation, and eventual coating failure as may occur with
      current plasma-sprayed hydroxapatite coating techniques.

PMID- 15162405
TI  - Reproductive toxic effect of bisphenol A dimethacrylate in mice.
AB  - The current study evaluated the effect of bisphenol A dimethacrylate (Bis-DMA) on
      mouse fertility. Adult male and female mice were exposed to intragastric Bis-DMA
      (0, 5, 25, and 100 microg/kg) daily for 28 days and then mated with sexually
      mature untreated mice and after mating fertility was assessed. Females mated by
      males that had been exposed to Bis-DMA had significant reductions in pregnancy
      rates and significant increases in the total number of resorptions out of the
      total number of implantations. Bis-DMA exposed males had significant reductions
      in body weights and relative testes weights and significant increases in seminal
      vesicle and preputial gland weights. Testicular and epididymal sperm counts as
      well as the efficiency of sperm production were also significantly reduced in
      these groups. Female mice exposed to Bis-DMA showed significant reductions in
      pregnancy rates, number of implantation sites, number of viable fetuses, and
      total number of resorptions out of the total number of implantations. Significant
      reductions in the body weights were observed at all doses, and significant
      increases were found in the relative weights of the ovaries and the uterus. The
      results suggest that Bis-DMA has adverse effects on the fertility and
      reproductive systems of male and female mice.

PMID- 15162407
TI  - Human alveolar bone cell adhesion and growth on ion-implanted titanium.
AB  - Surface characteristics play a vital role in determining the biocompatibility of
      materials used as bone implants. Calcium ion implantation of titanium was
      previously reported to enhance osseointegration and bone formation in vivo,
      although the lack of consistent and reproducible effects highlight the need to
      understand the basic mechanisms involved in the response of target cells to such
      surfaces. The aim of this study was therefore to measure the precise effects of
      ion implantation of titanium on bone cells in vitro. Alveolar bone cells were
      seeded on the surface of polished titanium disks implanted with calcium,
      potassium, and argon ions. Using radioisotopically tagged bone cells, the results
      showed that although the calcium ion implanted surface reduced cell adhesion, it
      nevertheless significantly enhanced cell spreading and subsequent cell growth. In
      contrast, few differences in bone cell behavior were observed between the
      potassium- and argon-implanted titanium and the control nonimplanted titanium
      disks. These findings suggest the possibility that the calcium-implanted surface
      may significantly affect the biocompatibility of titanium implants by enhancing
      bone cell growth. Surface modification by ion implantation could thus prove to be
      a valuable tool for improving the clinical efficacy of titanium for bone repair
      and regeneration in vivo.

PMID- 15162406
TI  - Inhibition of macrophage development and foreign body giant cell formation by
      hydrophilic interpenetrating polymer network.
AB  - The ability of monocytes to adhere, differentiate into macrophages, and fuse to
      form foreign body giant cells (FBGCs) on an implanted material surface is a
      critical step toward biomaterial degradation. Novel homogeneous surfaces were
      utilized to mediate adhesion. These surfaces consisted of N-(2 aminoethyl)-3
      aminopropyltrimethoxysilane (EDS) and an interpenetrating polymer network (IPN)
      of polyacrylamide and poly(ethylene glycol). These surfaces were designed to
      control cell adhesion and morphology and mediate cell differentiation,
      activation, metabolic ability, and apoptosis, resulting in a reduced or
      controlled inflammatory response. The EDS surface promotes cell adhesion and the
      IPN minimizes protein adsorption and subsequent cell adhesion. Both surfaces had
      similar cellular adhesion rates at each respective time point. However, the
      adherent macrophage morphology was similar at 2 h and day 3, and at days 7 and 10
      adherent macrophages on the EDS surface formed FBGCs (46% at day 7 and 40% at day
      10). Adherent cells on the IPN surface did not form FBGCs but instead formed
      monocyte aggregates (73% of adherent cells formed aggregates at day 7 and 63% at
      day 10). It is indicated that the two surface chemistries differentially
      controlled monocyte differentiation into macrophages and subsequent macrophage
      fusion to form FBGCs.

PMID- 15162409
TI  - Ultrastructural comparison of dissolution and apatite precipitation on
      hydroxyapatite and silicon-substituted hydroxyapatite in vitro and in vivo.
AB  - Recent histological studies have demonstrated that the substitution of silicate
      ions into hydroxyapatite (HA) significantly increases the rate of bone apposition
      to HA implants. The enhanced bioactivity of silicon-substituted HA (Si-HA) over
      pure HA has been attributed to the effect of silicate ions in accelerating
      dissolution. In the present study, high-resolution transmission electron
      microscopy (HR-TEM) was employed to compare dissolution of HA and Si-HA in an
      acellular simulated body fluid (SBF) to dissolution in an in vivo model. HR-TEM
      observations confirmed a difference in morphology of apatite precipitates in vivo
      and in SBF: apatite deposits were platelike in vivo and nodular in SBF.
      Compositional mapping suggested that preferential dissolution of silicon from the
      implant promotes the nucleation of carbonate apatite around the implant. The in
      vivo findings illustrated an absence of dissolution at the bone-HA or Si-HA
      interface, whereas dissolution was extensive from within the implant. The amount
      of dissolution in acellular SBF was similar to dissolution from within the
      implant, although the site at which the dissolution nucleates was different:
      dissolution predominates at the crystallite surfaces in SBF, whereas grain
      boundary dissolution predominates in vivo. These findings suggest that proteins
      in the in vivo milieu modify the processes of dissolution from the implant.

PMID- 15162408
TI  - Response of heterograft heart valve biomaterials to moderate cyclic loading.
AB  - We have recently demonstrated that noncalcific tissue damage can lead to
      significant collagen degradation in clinically explanted bioprosthetic heart
      valves (BHVs). In the present study we quantified the early response of
      glutaraldehyde treated bovine pericardium (GLBP) to cyclic tensile loading to
      begin to elucidate the mechanisms of noncalcific tissue degeneration in BHV
      biomaterials. GLBP specimens were cycled at 30 Hz to a maximum uniaxial strain of
      16% (corresponding to approximately 1-MPa peak stress), with the loading
      direction parallel to the preferred collagen fiber (PD) direction. After 30 x
      10(6) cycles, specimens were subjected to biaxial mechanical testing, then cycled
      until 65 x 10(6) cycles. The results indicated a permanent change in the unloaded
      tissue dimensions of +7.1% strain in the PD direction and -7.7% strain in the
      cross fiber direction (XD) after 65 x 10(6) cycles and an increase of the
      collagen crimp period from 40.6 to 45.2 microm by 65 x 10(6) cycles (p = 0.05).
      Fourier transform IR spectroscopy analysis indicated that cyclic fatigue of GLBP
      leads to both collagen conformational changes and early denaturation.
      Furthermore, no significant changes in areal strain were found under 1-MPa
      equibiaxial stress, indicating that cyclic loading changed the collagen fiber
      orientation but not the overall tissue compliance. These observations suggest
      that while deterioration of collagen begins immediately, fiber straightening and
      reorientation dominates the changes in the mechanical behavior up to 65 x 10(6)
      cycles. The present study underscores the complexity of the response of
      biologically derived biomaterials to cyclic mechanical loading. Improved
      understanding of these phenomena can potentially guide the development of novel
      chemical treatment methods that seek to improve BHV durability by minimizing
      these degenerative processes.

PMID- 15162410
TI  - The effect of basic fibroblast growth factor on bone regeneration when released
      from a novel in situ setting tricalcium phosphate cement.
AB  - The osteostimulative effect of the basic fibroblast growth factor is well known,
      but it is dose dependent, and release kinetic depends on interactions with the
      used carrier. The aim of our study was to determine the osteostimulative effect
      of a composite, consisting of an in situ setting tricalcium phosphate cement and
      basic fibroblast growth factor. A trepanation defect of 1.5 mm in the femur
      diaphysis of Sprague-Dawley rats was filled with the in situ setting TCP cement
      combined with 0, 0.25, 2.5, or 25 microg rh bFGF, an autologous bone graft or
      left empty. The rats were euthanized after 1 and 3 weeks and examined by
      radiography, histology, histomorphometry, and bending test. The data were
      analyzed by the Wilcoxon and Kruskal-Wallis test. All TCP groups with or without
      bFGF showed a good bony ingrowth with a close bone-cement contact. Osseous
      ingrowth was not influenced by the addition of the different doses of bFGF as
      shown by histomorphometry. Also, mechanical strength was not affected. In
      conclusion, the combination of this in situ setting cement with bFGF is not
      useful for clinical application. The reason of these negative results remains
      unclear: the osteostimulative effect of bFGF is well known, and the TCP-cement
      was used as a carrier for rhBMP-2 successfully. These negative results may be due
      to a too slow or too fast release of bFGF from the cement.

PMID- 15162411
TI  - A molecular modeling study of the effect of surface chemistry on the adsorption
      of a fibronectin fragment spanning the 7-10th type III repeats.
AB  - Although it is well documented that proteins adsorb onto biomaterial surfaces,
      relatively little is quantitatively understood about the effects of adsorption on
      protein orientation and conformation. Because this is the primary determining
      factor of protein bioactivity, the ability to accurately predict a protein's
      orientation and conformation following adsorption will be essential for the
      rational design of biomaterial surfaces to control biological responses. Force
      field-based computational chemistry methods provide an excellent means to
      theoretically address this issue, with the nontrivial requirement that the force
      field must be tailored to appropriately represent protein adsorption behavior.
      Accordingly, we have modified an existing force field (CHARMm) based on
      semiempirical quantum-mechanical peptide adsorption data to enable it to simulate
      protein adsorption behavior in an implicit aqueous environment. This modified
      force field was then applied to predict the adsorption behavior of the 7-10 type
      III repeats of fibronectin on functionalized surfaces. Predicted changes in
      adsorption energy and adsorption-induced conformation as a function of surface
      chemistry were found to correlate well with experimentally observed trends for
      these same systems. This work represents a first attempt towards the development
      of a molecular mechanics force field that is specifically parameterized to
      accurately simulate protein adsorption to biomaterial surfaces.

PMID- 15162412
TI  - In vitro and in vivo behavior of self-reinforced bioabsorbable polymer and self
      reinforced bioabsorbable polymer/bioactive glass composites.
AB  - The aim of this study was to investigate the in vitro and in vivo properties and
      degradation of (1) self-reinforced (SR) lactide copolymer, P(L/DL)LA 70:30, and
      (2) SR composites of the same polylactide and bioactive glass 13-93. The
      following three polymer and polymer-bioactive glass samples were studied: SR
      PLA70, SR-PLA70 + BaG15s, and SR-PLA70 + BaG20c. In vitro behavior was studied in
      a phosphate-buffered saline for 87 weeks at 37 degrees +/- 1 degrees C and a pH
      of 7.4 +/- 0.2. In vivo behavior was studied by implanting the rods in the dorsal
      subcutaneous tissue of rats (SR-PLA70 + BaG20c) or rabbits (SR-PLA70 and SR-PLA70
      + BaG15s) for 48 weeks. The degradation of the specimens was evaluated by
      measuring the changes in mechanical properties, crystallinity and molecular
      weight of polymer, water absorption, weight loss, and structural changes. Results
      showed that the addition of bioactive glass filler modified the degradation
      kinetics and material morphology.

PMID- 15162413
TI  - Biocompatibility and biodegradation of a bone composite containing tricalcium
      phosphate and genipin crosslinked gelatin.
AB  - A biodegradable composite (GGT) containing tricalcium phosphate ceramic particles
      and genipin crosslinked gelatin was developed for use as a bone substitute. The
      objective of this study was to assess the biocompatibility and the
      osteoconductivity of the GGT composite on new bone formation in vitro.
      Additionally, biodegradation and biocompatibility of the GGT composite in animals
      were investigated. Results of the GGT composites cocultured with osteoblasts
      showed that the concentration of genipin used as a crosslinking agent should be
      <0.5 wt % to avoid cytotoxicity. For in vivo degradation studies, we found that
      when the concentration of genipin in the composite <0.5 wt % was not enough to
      fully crosslink the gelatin, it results in a rapid degradation of the gelatin
      genipin mixture. However, we also found that the foreign body capsule surrounding
      the GGT composite containing 1.0 wt % of the genipin was much thicker than that
      in the other three groups, that is, the composites containing 0.05, 0.1, and 0.5
      wt % of the genipin. We therefore concluded that the ideal concentration of
      genipin used in the GGT was 0.5 wt %. Finally, we examined the organ culture
      units, which were maintained in cultured medium for 5 weeks. Morphology of tissue
      was observed and the quantitative evaluation of the regenerated bone was
      determined. We found that the GGT composites containing 0.5 wt % of the genipin
      had an excellent biocompatibility and could produce osteoconduction for the
      regenerating bone tissues.

PMID- 15162414
TI  - Comparative study of the in vitro apatite-forming ability of poly(epsilon
      caprolactone)-silica sol-gels using three osteoconductivity tests (static,
      dynamic, and alternate soaking process).
AB  - The in vitro apatite-forming ability of poly(epsilon-caprolactone) (70 wt %)
      silica sol-gels, with hydroxyl and triethoxysilane end-groups with potential use
      in bone repair have been assessed using static and dynamic osteoconductivity
      tests. Diffuse reflectance infrared spectroscopy, scanning electron microscopy,
      and microanalysis techniques were used to observe and characterize precipitates
      formed on the material's surface. An apatite layer was observed to form on both
      of the composites' surface. However, variations were observed according to the
      test method used, in accordance with other studies on bioactive ceramics. A third
      method, the "alternate soaking process" (ASP) was developed to provide rapid
      results and quantify the amount of calcium-containing precipitates formed on the
      surface of potentially "bioactive" materials. The results presented here show
      that for a material to be bioactive and have the ability to form a precipitate
      containing calcium and phosphate ions, levels of calcium ions measured by a
      complexometric assay should be significantly higher than the level of 5
      microg/cm(2). This level of calcium ions was obtained after 20 ASP cycles for the
      hydroxyl and triethoxysilane end-capped poly(epsilon-caprolactone) samples that
      did not form precipitates on their surfaces even after >50 ASP cycles. For the
      two sol-gel silica composites containing approximately 70% hydroxyl and
      triethoxysilane poly(epsilon-caprolactone), there was no significant difference
      in the amount of calcium-containing precipitate as observed using the in vitro
      apatite-forming ability tests suggesting that polymer end-group modification is
      not detrimental to the apatite-forming ability of such composites.

PMID- 15162415
TI  - Novel polymer-synthesized ceramic composite-based system for bone repair: an in
      vitro evaluation.
AB  - The emergence of synthetic bone repair scaffolds has been necessitated by the
      limitations of both autografts and allografts. Several candidate materials are
      available including degradable polymers and ceramics. However, these materials
      possess their own limitations that at least in part may be overcome by combining
      the two materials into a composite. Toward that end, a novel approach to forming
      a polymer/ceramic composite has been developed that combines degradable
      poly(lactide-co-glycolide) microspheres and a poorly crystalline calcium
      phosphate that is synthesized within the microspheres, which are then fused
      together to form a porous three-dimensional scaffold for bone repair. The design,
      fabrication, and characterization of the composite microspheres, the calcium
      phosphate formed within these microspheres, and the formation of scaffolds were
      studied. The calcium phosphate formed was analyzed by x-ray diffraction, Fourier
      transform infrared spectroscopy, and energy dispersive spectroscopy, and was
      shown to be similar to native bone in both composition and crystallinity by
      controlling certain processing parameters such as mixing time, solution pH, and
      mixing temperature. Scaffolds with porous interconnected structures and
      mechanical properties in the range of trabecular bone were fabricated via precise
      control of polymer/ceramic ratios within the microspheres and scaffold heating
      times. This composite scaffold represents a new and important vehicle for bone
      tissue engineering.

PMID- 15162416
TI  - Bone formation in polymeric scaffolds evaluated by proton magnetic resonance
      microscopy and X-ray microtomography.
AB  - Magnetic resonance microscopy (MRM) and X-ray microtomography (XMT) were used to
      investigate de novo bone formation in porous poly(ethyl methacrylate) (PEMA)
      scaffolds, prepared by a novel co-extrusion process. PEMA scaffolds were seeded
      with primary chick calvarial osteoblasts and cultured under static conditions for
      up to 8 weeks. Bone formation within porous PEMA scaffolds was confirmed by the
      application of histologic stains to intact PEMA disks. Disks were treated with
      Alizarin red to visualize calcium deposits and with Sirius red to visualize
      regions of collagen deposition. DNA analysis confirmed that cells reached
      confluence on the scaffolds after 7 weeks in static culture. The formation of
      bone in PEMA scaffolds was investigated with water proton MRM. Quantitative MRM
      maps of the magnetization transfer ratio (MTR) yielded maps of protein
      deposition, and magnetic resonance (MR) relaxation times (T1 and T2) yielded maps
      of mineral deposition. The location of newly formed bone and local mineral
      concentrations were confirmed by XMT. By comparing MRM and XMT data from selected
      regions-of-interest in one sample, the inverse relationship between the MR
      relaxation times and mineral concentration was validated, and calibration curves
      for estimating the mineral content of cell-seeded PEMA scaffolds from
      quantitative MRM images were developed.

PMID- 15162417
TI  - On the role of CO2 laser treatment in the human serum albumin and human plasma
      fibronectin adsorption on zirconia (MGO-PSZ) bioceramic surface.
AB  - The nature of the surface strongly influences the composition and recognizability
      of the adsorbed protein layer, which in turn affects the subsequent cellular
      interactions. Thus, to understand the biological response to a material,
      especially in vitro, one must fully understand the nature of the adsorbed protein
      film that forms on the material. This study investigates the fundamental
      interactions between the human serum albumin (no-cell adhesive) and human plasma
      fibronectin and bioinert ceramic following CO(2) laser treatment. The analysis of
      the albumin and fibronectin adsorption was conducted on the untreated and CO(2)
      laser-modified magnesia partially stabilized zirconia (MgO-PSZ) bioceramic using
      an ellipsometry. It was found that the adsorptions of albumin and fibronectin
      were influenced by the surface properties. The albumin adsorption was affected by
      the surface roughness and wettability characteristics of the MgO-PSZ and
      decreased with these properties, while the fibronectin adsorption was increased
      with wettability characteristics and predominantly governed by this property.
      Moreover, the considerable change in the polar component of surface energy,
      gamma(sv) (p), and its effect on protein adsorption implied that the albumin and
      fibronectin adsorption on the MgO-PSZ surfaces was probably due to the polar and
      chemical interactions. The value of this work is to provide a novel technique and
      useful information for manipulating protein adsorption and thereof cellular
      interactions.

PMID- 15162419
TI  - Mini-review: The nuclear protein HMGB1 as a proinflammatory mediator.
AB  - The intranuclear architectural protein that is termed high mobility group box
      chromosomal protein 1 (HMGB1) was recently identified as a potent proinflammatory
      mediator when present extracellularly. HMGB1 has been demonstrated to be a long
      searched-for nuclear danger signal passively released by necrotic, as opposed to
      apoptotic, cells that will induce inflammation. Furthermore, HMGB1 can also be
      actively secreted by stimulated macrophages or monocytes in a process requiring
      acetylation of the molecule, which enables translocation from the nucleus to
      secretory lysosomes. Subsequent transport out of the cells depends on a secretion
      signal mediated by either extracellular lysophophatidyl-choline or ATP. HMGB1
      passively released from necrotic cells and HMGB1 actively secreted by
      inflammatory cells are thus molecularly different. Extracellular HMGB1 acts as a
      cytokine by signaling via the receptor for advanced glycated end-products and via
      members of the Toll-like receptor family. The initiated inflammatory responses
      include the production of multiple cytokines, chemoattraction of certain stem
      cells, induction of vascular adhesion molecules and impaired function of
      intestinal epithelial cells. Therapeutic administration of HMGB1 antagonists
      rescues mice from lethal sepsis, even when initial treatment is delayed for 24 h
      after the onset of infection, establishing a clinically relevant therapeutic
      window that is significantly wider than for other known cytokines.

PMID- 15162420
TI  - Mini-review: Specificity and expression of CIITA, the master regulator of MHC
      class II genes.
AB  - The class II transactivator (CIITA) has been referred to as the "master control
      factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the
      specificity and function of CIITA grows, it is becoming increasingly evident that
      this sobriquet is entirely justified. First, despite extensive investigations,
      the major target genes of CIITA remain those implicated in the presentation of
      antigenic peptides by MHCII molecules. Although other putative target genes have
      been reported, the contribution of CIITA to their expression remains indirect,
      controversial or comparatively minor relative to its decisive role as a regulator
      of MHCII and related genes. Second, the most important parameter dictating MHCII
      expression is by far the expression pattern of the gene encoding CIITA (MHC2TA).
      The vast majority of signals that activate or repress MHCII expression under
      physiological and pathological situations converge on one or more of the three
      alternative promoters that drive transcription of the MHC2TA gene. In short, with
      respect to its specificity and its exquisitely controlled pattern of expression,
      CIITA is by a long stretch the single most important transcription factor for the
      regulation of genes required for MHCII-restricted antigen-presentation.

PMID- 15162421
TI  - Virus-specific CD8+ T lymphocytes within the normal human liver.
AB  - The frequency and phenotype of human antiviral memory CD8(+) T cells in blood are
      well studied, yet little is known about their distribution within tissues.
      Analysis of antiviral CD8(+) T cell populations derived from a unique set of
      normal liver and blood samples identified a consistent population of virus
      specific cells within the liver. In comparison to the circulating T cells, the
      liver-derived T cells were present at frequencies which were variably enriched
      compared to that in the blood, and showed significant differences with regard to
      the expression of CD45RA, CD45RO, CD95, CCR7, CD27 and CD28. The differences in
      these cell surface markers are consistent with a mature 'effector memory'
      phenotype of antigen-specific CD8(+) T cells within the liver. An enrichment of
      an activated subset of NKT cells (V alpha 24/V beta 11) was also observed, a
      finding which may be relevant to the regulation of the antiviral populations.

PMID- 15162422
TI  - Impact of early expression of TCR alpha chain on thymocyte development.
AB  - CD4(-)CD8(-) thymocytes expressing a transgenic T cell receptor (TCR) alpha chain
      have decreased capacity to give rise to CD4(+)CD8(+) thymocytes when compared
      with wild-type thymocytes. This inefficient CD4(-)CD8(-) to CD4(+)CD8(+)
      maturation is mediated by the transgenic TCR alpha chain pairing with endogenous
      TCR beta chain but not with endogenous TCR gamma chain. Comparison between TCR
      alpha chain-transgenic mice with or without a functional pre-TCR alpha (pT alpha
      ) chain reveals that the formation of transgenic alpha/endogenous beta TCR on
      CD4(-)CD8(-) thymocytes inhibits the formation of pre-TCR, but at the same time
      mediates CD4(-)CD8(-) to CD4(+)CD8(+) maturation in the absence of pre-TCR,
      albeit inefficiently. These results indicate that alpha beta TCR and pre-TCR
      provide different signals for thymocyte development. They also suggest that the
      precise regulation of the sequential rearrangements of TCR beta and alpha loci
      and the cellular expansion induced by the pre-TCR may both be evolved to ensure
      the efficient generation of mature alpha beta T cells.

PMID- 15162424
TI  - Extended presentation of specific MHC-peptide complexes by mature dendritic cells
      compared to other types of antigen-presenting cells.
AB  - Dendritic cells are known as the most potent antigen-presenting cells for the
      induction of T cell-mediated immune responses. To discriminate between the
      presentation of antigens and the co-stimulatory aspects of this high
      immunostimulatory capacity, we used recombinant antibodies with T cell receptor
      like specificity to detect defined MHC-peptide complexes on living cells. Mature
      human dendritic cells (mDC) were compared with immature DC (iDC), monocytes,
      CD4(+) T lymphocytes, melanoma cells, T2 cells and B lymphoblastoid cells for
      their capacity to present MHC class I-restricted tumor-associated T cell epitopes
      and were found to display the specific peptides two to six times longer than
      other cells. The most short-lived peptide had an average half-life of 8.7 h on
      mDCvs. 3.5 h on B lymphoblastoid cells, while the most long-lived peptide had a
      half-life of 118.5 h vs. 20.7 h on these two cell types. The decay kinetics of
      specific MHC-peptide complexes on iDC were among the fastest observed. The high
      potency of dendritic cells to induce specific T cell responses is thus based, in
      addition to the expression of co-stimulatory molecules, on an extended antigenic
      memory, which increases the likelihood and the extent of contacts between
      dendritic cells and antigen-specific T cells.

PMID- 15162423
TI  - CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act
      as principal antigen-presenting cells in leishmaniasis.
AB  - In the early phase of leishmaniasis three types of potential antigen-presenting
      cells, including epidermal Langerhans cells (LC), dermal dendritic cells (DC) and
      inflammatory DC, are localized at the site of infection. Therefore, it has been a
      central question which cell type is responsible for the initiation of a
      protective immune response. In the early stage of an anti-Leishmania immune
      response, detectable Leishmania major antigen was localized in the paracortex of
      the draining lymph nodes (LN). Characterization of antigen-positive cells showed
      that L. major co-localized with DC of a CD11c(+) CD8 alpha(-) Langerin(-)
      phenotype. To determine the area of antigen uptake, dermis or epidermis, and to
      further define the type of antigen-transporting cells, L. major was inoculated
      subcutaneously and concurrently LC were mobilized with fluorescein isothiocyanate
      (FITC). After 3 days, DC carrying L. major antigen were always FITC(-),
      indicating a dermal and not an epidermal origin. Moreover, addition of L. major
      antigen to ex vivo isolated CD8 alpha(-) and CD8 alpha(+) DC from the draining LN
      of L. major-infected C57BL/6 mice demonstrated that both DC subpopulations were
      able to stimulate antigen-specific T cell proliferation in vitro. Without
      addition of exogenous antigen only the CD8 alpha(-) Langerin(-) DC were capable
      of stimulating antigen-specific T cell proliferation. Thus, we demonstrate that
      CD8 alpha(-) Langerin(-) DC and not LC are the basis of the protective immune
      response to intracellular L. major parasites in vivo.

PMID- 15162426
TI  - Ultra-sensitive class I tetramer analysis reveals previously undetectable
      populations of antiviral CD8+ T cells.
AB  - A major breakthrough in cellular immunology has been the development of HLA class
      I tetramers to analyze CD8(+) T cell responses. However, in many situations,
      including persistent virus infection, specific T cell responses are rarely
      detected using this technology. This raises the question of whether such
      responses are 'deleted' (or 'exhausted') or present below the conventional
      detection limit for class I tetramer staining. In particular, persistent
      hepatitis C virus (HCV) infection is characterized by very weak or apparently
      absent specific CD8(+) T cell responses, even though they are readily detectable
      in acute disease. Therefore, we assessed the use of anti-PE-labeled magnetic
      beads to enrich tetramer-positive HCV-specific T cells and identify previously
      undetectable populations. Using the enrichment technique, HCV-specific T cells
      could be detected in the majority of infected individuals, whereas these
      responses were not detected using conventional tetramer staining (8/15 vs. 1/15;
      p=0.01). Magnetic enrichment could reliably detect very rare HCV-specific
      responses at frequencies of >0.0011% of CD8(+) T cells (approximately 1/million
      PBMC), and phenotypic analysis of these rare populations was possible. Therefore,
      this direct ex vivo technique revealed the persistence of very low frequencies of
      virus-specific CD8(+) T cells during chronic virus infection and is readily
      transferable to the study of other viral, self- or tumor-specific T cells.

PMID- 15162425
TI  - Interleukin-5 participates in the pathogenesis of ileitis in SAMP1/Yit mice.
AB  - SAMP1/Yit mice spontaneously develop ileitis resembling Crohn's disease (CD)
      without chemical or genetic manipulations. Since the focus of studies were Th1
      cytokines, only Th1-type T cells were thought to be responsible for intestinal
      inflammation in these mice. To further characterize the pathogenesis of this
      ileitis, we investigated the implication of Th2 cytokines in ileitis of SAMP1/Yit
      mice. The expression of chemokine receptors (CCR) associated with both Th1 and
      Th2 lymphocytes, such as CCR2, CCR3, CCR4, CCR5, and CCR8, was increased. Among
      cytokines, IL-5 was remarkably increased in Peyer's patches, mesenteric lymph
      nodes, and mucosa involved in ileitis. Furthermore, infiltration of numerous
      eosinophils in ileitis was histologically evident. Severe combined
      immunodeficiency mice injected intraperitoneally with CD4(+) cells from SAMP1/Yit
      mice developed colitis and ileitis, with the infiltration of eosinophils.
      Administration of anti-IL-5 antibodies significantly attenuated ileitis in these
      mice. We suggest that IL-5 participates in the pathogenesis of ileitis and that
      anti-IL-5 antibodies are potentially useful for immunotherapy in CD patients.
      This is the first demonstration that IL-5 is crucial for the development of
      ileitis in this mouse model of CD.

PMID- 15162427
TI  - Impaired migration of NOD mouse thymocytes: a fibronectin receptor-related
      defect.
AB  - We previously showed intrathymic alterations in non-obese diabetic (NOD) mice,
      including the appearance of giant perivascular spaces, filled with mature
      thymocytes, intermingled with an extracellular matrix network. This raised the
      hypothesis of a defect in thymocyte migration with partial arrest of exiting
      thymocytes in the perivascular spaces. Herein, we investigated the expression of
      receptors for fibronectin [very late antigen (VLA)-4 and VLA-5] and laminin (VLA
      6), known to play a role in thymocyte migration. When compared with two normal
      and one other autoimmune mouse strains, a decrease of VLA-5 expression in NOD
      thymocytes was noticed, being firstly observed in late CD4/CD8 double-negative
      cells, and more pronounced in mature CD4(+) and CD8(+) thymocytes. Functionally,
      thymocyte exit from the lymphoepithelial complexes, the thymic nurse cells, was
      reduced. Moreover, NOD thymocyte adhesion to thymic epithelial cells as well as
      to fibronectin was diminished, and so was the migration of NOD thymocytes through
      fibronectin-containing transwell chambers. In situ, intra-perivascular space
      thymocytes were VLA-5-negative, suggesting a correlation between the thymocyte
      arrest within these structures and loss of VLA-5 expression. Overall, our data
      reveal impairment in NOD thymocyte migration, and correspond to the first
      demonstration of a functional fibronectin receptor defect in the immune system.

PMID- 15162429
TI  - Comparative genomics of the Mill family: a rapidly evolving MHC class I gene
      family.
AB  - Mill (MHC class I-like located near the leukocyte receptor complex) is a novel
      family of class I genes identified in mice that is most closely related to the
      human MICA/B family. In the present study, we isolated Mill cDNA from rats and
      carried out a comparative genomic analysis. Rats have two Mill genes orthologous
      to mouse Mill1 and Mill2 near the leukocyte receptor complex, with expression
      patterns similar to those of their mouse counterparts. Interspecies sequence
      comparison indicates that Mill is one of the most rapidly evolving class I gene
      families and that non-synonymous substitutions occur more frequently than
      synonymous substitutions in its alpha 1 domain, implicating the involvement of
      Mill in immune defenses. Interestingly, the alpha 2 domain of rat Mill2 contains
      a premature stop codon in many inbred strains, indicating that Mill2 is not
      essential for survival. A computer search of the database identified a horse Mill
      like expressed sequence tag, indicating that Mill emerged before the radiation of
      mammals. Hence, the failure to find Mill in human indicates strongly that it was
      lost from the human lineage. Our present work provides convincing evidence that
      Mill is akin to the MICA/B family, yet constitutes a distinct gene family.

PMID- 15162428
TI  - Notch1 expression on T cells is not required for CD4+ T helper differentiation.
AB  - Notch1 proteins are involved in binary cell fate decisions. To determine the role
      of Notch1 in the differentiation of CD4(+) Th1 versus Th2 cells, we have compared
      T helper polarization in vitro in naive CD4(+) T cells isolated from mice in
      which the N1 gene is specifically inactivated in all mature T cells. Following
      activation, Notch1-deficient CD4(+) T cells transcribed and secreted IFN-gamma
      under Th1 conditions and IL-4 under Th2 conditions at levels similar to that of
      control CD4(+) T cells. These results show that Notch1 is dispensable for the
      development of Th1 and Th2 phenotypes in vitro. The requirement for Notch1 in Th1
      differentiation in vivo was analyzed following inoculation of Leishmania major in
      mice with a T cell-specific inactivation of the Notch1 gene. Following infection,
      these mice controlled parasite growth at the site of infection and healed their
      lesions. The mice developed a protective Th1 immune response characterized by
      high levels of IFN-gamma mRNA and protein and low levels of IL-4 mRNA with no IL
      4 protein in their lymph node cells. Taken together, these results indicate that
      Notch1 is not critically involved in CD4(+) T helper 1 differentiation and in
      resolution of lesions following infection with L. major.

PMID- 15162430
TI  - The alpha v beta 3 integrin as a tumor homing ligand for lymphocytes.
AB  - Despite the presence of tumor-specific effector cells in the circulation of
      cancer patients, the immune response of the majority of these patients is not
      sufficient to prevent the growth and spread of their tumors. That tumor cells can
      be killed in vitro by tumor-reactive cytotoxic T cells is testimony to the fact
      that the tumors are not inherently resistant to T cell killing, but rather that
      there is a failure in immune recognition and effector cell activation. Many
      reasons for this failure of the body's defense system have been suggested,
      including the inability of tumor-reactive lymphocytes to migrate to tumor tissue.
      Here we designed a strategy to improve homing of primary lymphocytes into
      vascularized tumors. As a homing molecule we selected the integrin alpha v beta 3
      since it is expressed by angiogenic vascular endothelium in tumors. To promote
      lymphocyte adhesion to alpha v beta 3 we "painted" primary lymphocytes with a
      recombinant, glycosylphosphatidylinositol-linked high-affinity ligand for alpha v
      beta 3. These painted lymphocytes specifically bound to alpha v beta 3 in vitro
      and homed to vascularized, solid tumors in vivo. This novel strategy may provide
      a significant advance in anti-tumor treatment such as adoptive immune therapy.

PMID- 15162431
TI  - Synthesis of several chemokines but few cytokines by primed uncommitted precursor
      CD4 T cells suggests that these cells recruit other immune cells without exerting
      direct effector functions.
AB  - Antigen-stimulated naive CD4 T cells may differentiate into effector T cells such
      as Th1 and Th2 cells, or may remain as proliferating but uncommitted, primed,
      precursor cells (Thpp cells) that can subsequently differentiate into Th1 or Th2
      cells in appropriate cytokine environments. To examine potential Thpp effector
      functions, we compared the genes expressed by mouse Thpp, naive, Th1 and Th2
      cells, using Affymetrix GeneChip and RNase Protection assays. Similar to naive
      CD4 T cells, Thpp cells expressed IL-2 but not the cytokines characteristic of
      differentiated Th1 or Th2 cells, such as IFN-gamma, IL-4, or IL-5. However, Thpp,
      Th1 and Th2 cells, but not naive cells, expressed several CC chemokines including
      CCL1/TCA3, CCL5/RANTES, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, and CCL9/MIP-1 gamma.
      Secretion of the corresponding proteins was confirmed by ELISA and Elispot.
      Consistent with this chemokine expression, supernatants of activated Thpp, Th1
      and Th2 cells but not naive CD4T cells induced pertussis toxin-sensitive
      chemotaxis of B and T cells. Supernatants of Thpp cells did not bias
      differentiation of naive CD4 T cells towards either Th1 or Th2 cells. The
      secretion of several chemokines, but few cytokines, by primed uncommitted Thpp
      cells suggests that their activation during an immune response may recruit
      effector cells without directly polarizing effector functions.

PMID- 15162432
TI  - Involvement of filamentous actin in setting the threshold for degranulation in
      mast cells.
AB  - Previous studies using cytochalasins and latrunculin B, inhibitors of actin
      polymerization, showed that filamentous (F)-actin had a negative regulatory role
      in Fc epsilon receptor I (Fc epsilon RI) signaling. How F-actin is involved in
      regulating the activation of mast cells is unknown. In this study we investigated
      the role of F-actin in mast cell activation induced by aggregation of the
      glycosylphosphatidylinositol (GPI)-anchored proteins Thy-1 and TEC-21, and
      compared it to activation via Fc epsilon RI. Pretreatment of rat basophilic
      leukemia cells with latrunculin B inhibited the Thy-1-induced actin
      polymerization and elevated the Thy-1-mediated secretory and calcium responses.
      Inhibition of actin polymerization followed by Thy-1 aggregation resulted in an
      increased tyrosine phosphorylation of Syk, phospholipase C gamma (PLC gamma),
      Gab2 and linker for activation of T cells (LAT) adapters, and some other
      signaling molecules. Enzymatic activities of phosphatidylinositol 3-kinase, PLC
      gamma, and phosphatase SHP-2 were also up-regulated, but tyrosine phosphorylation
      of ezrin was inhibited. Similar changes were observed in Fc epsilon RI-activated
      cells. Significant changes in intracellular distribution, tyrosine
      phosphorylation, and/or enzymatic activities of signaling molecules occurred in
      latrunculin-pretreated cells before cell triggering. The combined data suggest
      that actin polymerization is critical for setting the thresholds for mast cell
      signaling via aggregation of both Fc epsilon RI and GPI-anchored proteins.

PMID- 15162433
TI  - Induction of somatic hypermutation by antigen-specific B cell receptors in the
      human BL2 cell line.
AB  - The role of the B cell antigen receptor in the induction of somatic hypermutation
      is presently unclear. We established stable transfectants of the human BL2 cell
      line expressing hen-egg lysozyme-specific IgM or IgA and compared their ability
      to induce somatic hypermutation of the endogenous rearranged heavy-chain gene. We
      found that IgM and IgA were both able to induce somatic hypermutation in an
      antigen dose-independent manner. The mutations displayed most of the
      characteristics of somatic hypermutation in vivo. Notably, some replacements
      introduced stop codons in the coding region. Our data suggest that class-switched
      memory B cells may undergo somatic hypermutation. They also suggest that the
      transmembrane/cytoplasmic domains of the class-switched isotypes modulate the
      signaling and down-modulation activities of the BCR in an antigen dose-dependent
      manner.

PMID- 15162434
TI  - Loss or mismatch of MHC class I is sufficient to trigger NK cell-mediated
      rejection of resting lymphocytes in vivo - role of KARAP/DAP12-dependent and 
      independent pathways.
AB  - A prediction from the "missing self" hypothesis is that down-regulation of MHC
      class I on resting hematopoietic cells should be sufficient to make them
      susceptible to NK cell killing. Using a method enabling kinetic and quantitative
      assessments of NK cell-mediated rejection responses in vivo, we here show that
      resting hematopoietic cells from beta(2)-microglobulin-deficient (beta(2)m(-/-))
      mice were rapidly rejected in unmanipulated C57BL/6 (B6) mice. In situations of
      allelic MHC class I mismatches rejection occurred but required longer time.
      beta(2)m(-/-) donor cells pre-activated with concanavalin A were more efficiently
      eliminated compared to resting cells, as were MHC(-) tumor cells. When recipient
      mice were pretreated with an IFN inducer to activate NK cells, rejection was also
      enhanced. The signaling adaptor KARAP/DAP12 was dispensable for rejection of
      beta(2)m(-/-) cells (lacking MHC) but critical for rejection of BALB/c cells
      (mismatched MHC) in unmanipulated B6 recipients. In contrast, B6 recipients with
      pre-activated NK cells rejected BALB/c cells in a KARAP/DAP12-independent
      fashion. Loss or mismatch of MHC class I in resting cells was thus sufficient to
      convey susceptibility to NK cell rejection. However, activation of the effector
      or the target enhanced rejection and shifted the balance between different
      signaling pathways involved.

PMID- 15162435
TI  - Characterization of novel antigens recognized by serum autoantibodies from anti
      CD1 TCR-transgenic lupus mice.
AB  - In this study, we further characterize the humoral autoimmune response in the
      recently described anti-CD1 autoreactive T cell receptor-transgenic mouse lupus
      model (CD1 lupus model). We discovered and characterized novel autoantigens,
      comprising a protein of 105 kDa (p105) and a novel RNA molecule of 140 base pairs
      (bp) that is likely associated with p105, and several additional factors with
      distinct biochemical properties. In the CD1 lupus model, lethally irradiated
      BALB/c/nu/nu mice were injected intravenously with sorted bone marrow cells and
      sorted splenic T cells from donor BALB/c mice expressing TCR alpha and beta
      transgenes that encode autoreactivity for CD1d. Adoptive hosts injected with the
      single-positive (CD4(+) and CD8(+)) subset of transgenic cells developed anti
      double-stranded DNA antibodies and a lupus-like illness. Sera were analyzed by
      Western blotting and immunoprecipitation. Antigens were characterized by
      biochemical and serological methods. Serum autoantibodies from 5 of 12 (42%) CD1
      lupus mice immunoprecipitated a 105-kDa protein, termed p105. p105 was associated
      with a small RNA of approximately 140 bp. Anti-p105 autoantibodies appeared early
      in the course of disease. Serological and biochemical characterization suggested
      that p105 was distinct from known lupus autoantigens of similar molecular masses,
      indicating that p105 represents a novel autoantigen in lupus.

PMID- 15162437
TI  - Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific.
AB  - The recognition of MHC class I molecules by killer cell immunoglobulin-like
      receptors (KIR) is central to the control of NK cell function and can also
      modulate the CTL activation threshold. Among KIR receptors, KIR3DL2 is thought to
      interact with HLA-A3 and -A11, although direct evidence has been lacking. In this
      study, we show that HLA-A3 and -A11 tetramers specifically bind to KIR3DL2*001
      transfectants and that this recognition is peptide-specific. Single amino acid
      substitutions in the nonamer peptide underline a critical role for residue 8 in
      recognition of KIR3DL2. However, the role of this interaction in vivo still
      remains to be established.

PMID- 15162436
TI  - Homophilic interaction of NTBA, a member of the CD2 molecular family: induction
      of cytotoxicity and cytokine release in human NK cells.
AB  - NK-T-B antigen (NTBA) is a CD2 family member that functions as a coreceptor in
      human NK cell activation. Several receptor/ligand interactions occur between
      different members of this molecular family. In this study, in order to identify
      the natural ligand of NTBA, we produced a chimeric protein formed by the NTBA
      extracellular region fused with the Fc portion of human IgG1 (termed NTBA-Fc*).
      NTBA-Fc* specifically binds to NTBA cell transfectants but not to cells
      transfected with other CD2 family members including CD2, CD48, CD84, CD150,
      CD229, and CD244. Moreover, NTBA-Fc* also binds to NTBA(+) but not to NTBA(-) T
      cell lines. Enzyme-linked immunosorbent assays, plasmon resonance analysis, as
      well as NTBA-Fc*-mediated down-regulation of NTBA surface expression further
      confirmed the occurrence of NTBA/NTBA homophilic interaction. Functionally, in NK
      cells, NTBA-Fc* promoted a strong production of IFN-gamma and TNF-alpha.
      Moreover, NTBA-transfected targets displayed increased susceptibility to NK
      mediated killing as compared to untransfected cells and this effect was
      specifically inhibited by anti-NTBA mAb. Altogether our data indicate that NTBA
      is characterized by self recognition.

PMID- 15162438
TI  - Small interference RNA modulation of IL-10 in human monocyte-derived dendritic
      cells enhances the Th1 response.
AB  - RNA interference technology has been used to modulate dendritic cell (DC)
      function by targeting the expression of genes such as IL-12 and NF-kappa B. In
      this paper, we demonstrate that transfection of DC with IL-10-specific double
      strands of small interference RNA (siRNA) resulted in potent suppression of IL-10
      gene expression without inducing DC apoptosis or blocking DC maturation.
      Inhibition of IL-10 by siRNA was accompanied by increased CD40 expression and IL
      12 production after maturation, which endowed DC with the ability to
      significantly enhance allogeneic T cell proliferation. IL-10 siRNA transfection
      did not affect MHC class II, CD86, CD83, or CD54 expression in mature DC. To
      further test the ability of IL-10 siRNA-treated DC to induce a T cell response,
      naive CD4 T cells were stimulated by autologous DC pulsed with KLH. The results
      indicated that IL-10 siRNA-transfected DC enhanced Th1 responses by increasing
      IFN-gamma and decreasing IL-4 production. These findings suggest the potential
      for a novel immunotherapeutic strategy of using IL-10 siRNA-transfected antigen
      presenting cells as vaccine delivery agents to boost the Th1 response against
      pathogens and tumors that are controlled by Th1 immunity.

PMID- 15162439
TI  - The CD200 and CD200 receptor cell surface proteins interact through their N
      terminal immunoglobulin-like domains.
AB  - CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts
      with a receptor on myeloid cells (CD200R) involved in regulation of macrophage
      function. Both CD200 and CD200R contain two Ig superfamily domains like many
      other leukocyte membrane proteins. Site-directed mutagenesis of CD200R showed
      that, like CD200, it interacted through its N-terminal domain. This indicated
      that the cell-cell interaction spans four Ig superfamily domains and this
      distance is similar to many interactions found between T cells and antigen
      presenting cells. This suggests that this topology is also important in
      interactions of CD200 on a variety of cells with CD200R on myeloid cells, and
      comparable contact sites may be important mediating regulation in other cell-cell
      interactions. The mutagenesis showed that the binding involved the predicted
      GFCC' face of its N-terminal domain, like that of CD200, suggesting that the
      interaction evolved from a homotypic interaction.

PMID- 15162440
TI  - AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase-2 mRNA
      by inhibiting mitogen-activated protein kinase p38.
AB  - Secretion of proinflammatory mediators by activated macrophages plays an
      important role in the immune response to Trypanosoma cruzi. We have previously
      reported that AgC10, a glycosylphosphatidylinositol-anchored mucin from T. cruzi,
      inhibits TNF secretion by activated macrophages (de Diego, J., Punzon, C.,
      Duarte, M. and Fresno, M., Alteration of macrophage function bya Trypanosoma
      cruzi membrane mucin. J. Immunol. 1997. 159: 4983-4989). In this report we have
      further investigated the molecular mechanisms underlying this inhibition. AgC10
      inhibited TNF, IL-10 and cyclooxygenase-2 (COX-2) synthesis by macrophages
      activated with LPS or LPS plus IFN-gamma in a dose-dependent manner. AgC10 did
      not affect other aspects of macrophage activation induced by LPS, such as
      inducible nitric oxide synthase (iNOS) expression. AgC10 also had no effect on
      TNF or COX-2 transcription or the induction of their promoters but inhibited the
      stability of TNF and COX-2 mRNA, which are regulated post-transcriptionally by
      the mitogen-activated protein kinase (MAPK) p38 pathway. AgC10 was found to
      inhibit both the activation and the activity of p38 MAPK, since MAPK activated
      protein kinase-2 (MAPKAP-K2 or MK-2) phosphorylation was also strongly inhibited.
      This led to TNF and COX-2 mRNA destabilization. In contrast, AgC10 did not affect
      p38 activation induced by TNF. Furthermore, AgC10 inhibition must lie upstream in
      the MAPK activation pathway by LPS, since this mucin also inhibited
      extracellularly regulated kinase (ERK) and Jun kinase (JNK)activation.

PMID- 15162441
TI  - HIV infection of primary human T cells is determined by tunable thresholds of T
      cell activation.
AB  - HIV infection of primary human T cells requires T cell activation signals.
      However, how strength, duration, and quality of TCR signals affect susceptibility
      of resting human T cells to HIV infection remains poorly understood. We found
      that the same threshold and duration of antigen signals that lead to optimal T
      cell activation are required for HIV to progress beyond the level of reverse
      transcription within resting T cells. Remarkably, sustained cytokine signaling
      from the IL-2 receptor following TCR triggering was critical in establishing
      productive infection. While blockade of TCR signaling pathways with inhibitors of
      the phosphatidylinositol 3-kinase pathway caused a partial pre-integration block,
      another inhibitor, rapamycin, completely suppressed the infection. In contrast,
      cyclosporin A or FK506, inhibitors of NFAT, failed to block infection if the T
      cells were pre-activated. Collectively, these results bring to light significant
      parallels between successful HIV infection and optimal thresholds of T cell
      activation. Furthermore, our results underscore the critical role of IL-2
      signaling in establishing productive HIV infection. These findings have important
      implications for our understanding of the complex interplay of HIV with host
      factors induced upon T cell activation.

PMID- 15162442
TI  - The small subset of CD56brightCD16- natural killer cells is selectively
      responsible for both cell proliferation and interferon-gamma production upon
      interaction with dendritic cells.
AB  - The encounter of NK cells with dendritic cells (DC) undergoing maturation may
      result in the induction of NK cell proliferation. Whether such proliferation
      involves most NK cells or just a subset has yet to be determined. In the present
      study we analyzed the nature of such proliferating NK cells by combining
      carboxyfluorescein succinimidyl ester staining and double-fluorescence
      cytofluorimetric analysis. Freshly isolated peripheral blood NK cells cultured
      with LPS and immature DC underwent proliferation; however, proliferating cells
      were confined to a minor NK cell subset. This subset is characterized by the
      CD56(bright)CD16(-)NKG2A(+)KIR(-) surface phenotype (KIR, killer Ig-like
      receptor). This was further confirmed by the fact that, after cell sorting, only
      the CD56(bright) NK cells were able to proliferate in response to the DC
      stimulus, whereas the CD56(dull) were not. We also provide evidence that the
      CD56(bright) subset is the main source of IFN-gamma-producing NK cells, upon
      interaction with DC. The CD56(bright)CD16(-) NK cells express a panel of surface
      molecules including CD62L, CCR7 and CXCR3 that may allow their homing either to
      secondary lymphoid compartments or to inflamed tissues. This implies that, in
      vivo, the interactions between DC undergoing maturation and CD56(bright) NK cells
      may occur in different tissues and have different functional implications.

PMID- 15162443
TI  - CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice.
AB  - Mechanisms responsible for the development of autoimmune skin disease in humans
      and animal models with lupus remain poorly understood. In this study, we have
      investigated the role of CD1d, an antigen-presenting molecule known to activate
      natural killer T cells, in the development of inflammatory dermatitis in lupus
      susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice
      carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d
      deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more
      frequent and more severe skin disease, with increased local infiltration with
      mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d
      deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the
      spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes.
      Furthermore, CD1d deficiency was associated with decreased T cell production of
      type 2 cytokines and increased or unchanged type 1 cytokines. These findings
      indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the
      mechanisms by which CD1d deficiency results in splenic T cell expansion and
      cytokine alterations, with increased dermal infiltration of dendritic cells and
      lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of
      inflammatory skin diseases.

PMID- 15162445
TI  - Allergen extracts directly mobilize and activate human eosinophils.
AB  - Allergic diseases are characterized by the presence of eosinophils, which are
      recruited to the affected tissues by chemoattractants produced by T cells, mast
      cells and epithelium. Our objective was to evaluate if allergens can directly
      activate human eosinophils. The capacity of purified allergen extracts to elicit
      eosinophil chemotaxis, respiratory burst, degranulation and up-regulation of the
      adhesion molecule complement receptor 3 (CR3) was determined in eosinophils
      isolated from healthy blood donors. Eosinophils stimulated with an extract from
      house dust mite (HDM) released the granule protein major basic protein (MBP) and
      up-regulated the surface expression of CR3. Cat allergen extracts also induced
      the up-regulation of CR3, but not the release of MBP; instead cat, as well as
      birch and grass allergens, elicited the release of eosinophil peroxidase (EPO).
      In addition, grass pollen extract caused the secretion of MBP. None of the
      allergens stimulated eosinophilic cationic protein release, nor production of
      free oxygen radicals. Both HDM and birch extracts were chemotactic for
      eosinophils. These findings establish that common aeroallergens can directly
      activate eosinophils in vitro. We propose that eosinophil activation in vivo is
      not exclusively mediated by cytokines and chemokines of the allergic inflammatory
      reaction, but could partly be the result of direct interaction between allergens
      and eosinophils.

PMID- 15162444
TI  - The survival effect of TNF-alpha in human neutrophils is mediated via NF-kappa B
      dependent IL-8 release.
AB  - The capacity of cytokines to modulate neutrophil apoptosis is thought to be a
      major factor influencing the resolution of granulocytic inflammation. We have
      previously shown that the late survival effect of TNF-alpha in human neutrophils
      involves activation of both NF-kappa B and phosphoinositide 3-kinase (PI3-kinase)
      pathways. In this study, we address how these pathways integrate to prevent cell
      death. In human neutrophils, TNF-alpha (200 U/ml) induced rapid I kappa B-alpha
      degradation, NF-kappa B activation and IL-8 release (31.8+/-5.4 pg/10(5) cells/2
      h), whereas GM-CSF (10 ng/ml) stimulated an equivalent IL-8 release (26.5+/-4.5
      pg/10(5) cells/2 h) without enhanced I kappa B-alpha degradation or NF-kappa B
      activation compared to control. Importantly, inhibition of PI3-kinase did not
      modify TNF-alpha -induced I kappa B-alpha degradation, yet fully inhibited the
      survival effect of both cytokines. Inhibition of I kappa B-alpha phosphorylation,
      PI3-kinase or ERK1/2 activation blocked IL-8 release by both cytokines. Blocking
      IL-8 activity by inhibiting its synthesis or by using a neutralizing antibody
      enhanced the early pro-apoptotic effect of TNF-alpha and inhibited its late
      survival effect without affecting GM-CSF-induced survival. These data suggest
      that cross-talk between NF-kappa B and PI3-kinase pathways in TNF-alpha 
      stimulated neutrophils results from NF-kappa B/ERK1/2-dependent IL-8 production
      which acts in an autocrine manner to drive PI3-kinase-dependent survival. In
      contrast, GM-CSF-mediated survival does not involve NF-kappa B activation or IL-8
      release.

PMID- 15162446
TI  - Interferon gamma suppresses glucocorticoid augmentation of macrophage clearance
      of apoptotic cells.
AB  - One of beneficial effects of glucocorticoids (GC) in inflammation may be the
      augmentation of macrophages' capacity for phagocytosis of apoptotic cells, a
      process that has a central role in resolution of inflammation. Here we define the
      phenotype of GC-treated monocyte-derived macrophages, comparing to IFN-gamma
      treated and IL-4-treated monocyte-derived macrophages and combinatorial
      treatment. Our data indicate that the cytokine microenvironment at an
      inflammatory site will critically determine monocyte functional capacity
      following treatment with GC. In particular, whilst GC exert dominant regulatory
      effects over IFN-gamma in terms of cell surface receptor repertoire and
      morphology, the acquisition of a macrophage capacity for clearance of apoptotic
      cells is prevented by combined treatment. In terms of mechanism, GC augmentation
      of phagocytosis was reversed even when monocytes were pre-incubated with GC for
      the first 24 h of culture, a period that is critical for induction of a highly
      phagocytic macrophage phenotype. These findings have important implications for
      the effectiveness of GC in promoting acquisition of a pro-phagocytic macrophage
      phenotype in inflammatory diseases associated with high levels of IFN-gamma

PMID- 15162447
TI  - Activated T killer cells induce apoptosis in lung epithelial cells and the
      release of pro-inflammatory cytokine TNF-alpha.
AB  - Apoptosis is thought to be involved in lung epithelial cell damage in acute
      respiratory distress syndrome and interstitial pneumonia. Both the role of
      apoptosis and its underlying molecular mechanisms in human lung tissue remain
      unclear. To address these issues, we developed an in vitro assay in which a human
      lung epithelial cell line and a staphylococcal enterotoxin B (SEB)-reactive human
      CD8(+) CTL line were co-cultured in the presence of SEB. SEB-stimulated CD8(+)
      CTL induced apoptosis in the lung epithelial cell line primarily through the
      perforin/granzyme-mediated pathway. In these cells, apoptosis was initially
      independent of death receptor pathways. We also tested the effect of IFN-gamma on
      modulation of apoptosis in lung epithelial cells. In IFN-gamma-pretreated lung
      epithelial cells, CD95 (APO-1/Fas) activation as well as TNF-related apoptosis
      inducing ligand (TRAIL) receptor and TNFR activation led to apoptosis.
      Furthermore, we found that the interaction of SEB-stimulated CD8(+) CTL with lung
      epithelial cells induced an increase in TNF-alpha secretion. These results
      suggest an important role for bacterial superantigen-reactive CD8(+) CTL in
      induction of lung epithelial cell apoptosis and in modulation of inflammatory
      processes in lung tissue.

PMID- 15162448
TI  - In vitro laser ablation of laboratory developed biofilms using an Nd:YAG laser of
      532 nm wavelength.
AB  - We studied the laser ablation of laboratory-developed biofilm on titanium and
      glass surfaces. Specifically, Pseudoalteromonas carrageenovora, a marine biofilm
      forming bacterium was used to generate laboratory biofilm. Two fluences, 0.05 and
      0.1 J/cm(2) and three durations of irradiation, 30 s, 5 min, and 10 min were
      tested using an Nd;YAG laser of 532 nm wavelength (in the green light area).
      Nonirradiated coupons with biofilm served as control. The biofilm removal
      efficiency increased with the increase in laser fluence and duration of
      irradiation. The maximum biofilm area cover on control coupons of glass and
      titanium was 62.5 and 76.0%, respectively. Upon irradiation with fluence 0.1
      J/cm(2) for the very short duration of 30 s, this reduced to 5.6 and 12.4% and at
      10 min to 2.17 and 0.7% on glass and titanium coupons, respectively, while the
      controls did not show any reductions (62.5 and 76.0% respectively, for glass and
      titanium coupons). The biofilm TRC (Total Resuscitated Cells) reduction during
      this period was even more prominent than the area cover, indicating that the
      remaining biofilm portions on coupons after irradiation were largely composed of
      dead bacterial cells. The TRC in the irradiation chamber medium for short
      durations of irradiation showed a significant increase, indicating that the laser
      irradiation removed live bacteria from the biofilm. The re-growth of the
      resuscitated cells showed they could grow like the control cells but with a
      significant lag. The laser's efficiency in the removal of biofilm was better seen
      on titanium coupons than on glass. Our results showed that a low-power pulsed
      laser irradiation could be used to remove biofilm formed on hard surfaces.

PMID- 15162449
TI  - Recombinant antigen from Helicobacter pylori urease as vaccine against H. pylori
      associated disease.
AB  - It is well documented that the enzymatic active site of Helicobacter pylori
      urease is present in the beta-subunit. An important sequence of 135 amino acids
      of the beta-subunit was determined from the structure of H. pylori urease and by
      a homology-based study of the urease of other bacteria and plants. The sequence
      (UreB) was expressed in Escherichia coli as a recombinant fusion protein with
      glutathione-S-transferase (GST). Seventeen monoclonal antibodies, UA-1-17, were
      produced using the UreB-GST as the immunogen. The obtained monoclonal antibodies
      showed a high specificity to UreB, and some of the MAbs cross-reacted with Jack
      bean urease. About 70% of the established MAbs displayed an inhibitory effect on
      the enzymatic activity of the urease. Among them, UA-15 MAb could reduce the
      activity by 53% and it immunologically binds to the bacterium infecting the human
      stomach mucosa. The antiserum induced by immunization with a recombinant UreB-GST
      into rabbits displayed a specific binding to mucosal surfaces of the human
      stomach infected with the pathogen H. pylori. Moreover, the antiserum suppressed
      the enzymatic activity of H. pylori urease, while the purified H. pylori urease
      could not induce such an antiserum.

PMID- 15162450
TI  - Encapsulating chondrocytes in degrading PEG hydrogels with high modulus:
      engineering gel structural changes to facilitate cartilaginous tissue production.
AB  - A major challenge when designing cell scaffolds for chondrocyte delivery in vivo
      is creating scaffolds with sufficient mechanical properties to restore initial
      function while simultaneously controlling temporal changes in the gel structure
      to facilitate tissue formation. To address this design challenge, degradable
      photocrosslinked hydrogels based on poly(ethylene glycol) were investigated. To
      alter the gel's initial mechanical properties, hydrogels were fabricated by
      varying the initial macromer concentration from 10% to 15% to 20%. A twofold
      increase in macromer concentration resulted in an eightfold increase in the
      initial compressive modulus from 60 to 500 kPa. Gel degradation was tailored by
      incorporating fast-degrading crosslinks that enable maximal extracellular matrix
      (ECM) diffusion with time and a minimal number of nondegrading (or slowly
      degrading) crosslinks to maintain scaffold integrity and prevent complete gel
      erosion during tissue formation. Chondrocytes encapsulated in these gels produced
      cartilaginous tissue rich in glycosaminoglycans and collagen as seen
      biochemically and histologically. Interestingly, mass loss appeared to more
      closely match tissue secretion in gels fabricated from a 15% macromer
      concentration. However, the spatial ECM distribution was grossly similar in all
      three gels. By tailoring gel degradation and controlling network evolution during
      degradation, gels with optimal properties can be fabricated to support initially
      physiologic compressive loads while simultaneously supporting the formation of a
      neotissue.

PMID- 15162451
TI  - Rapid chromatography for evaluating adsorption characteristics of cellulase
      binding domain mimetics.
AB  - The cost of cellulolytic enzymes is one barrier to the economic production of
      fermentable sugars from lignocellulosic biomass for the production of fuels and
      chemicals. One functional characteristic of cellulolytic enzymes that improves
      reaction kinetics over mineral acids is a cellulose binding domain that
      concentrates the catalytic domain to the substrate surface. We have identified
      maleic acid as an attractive catalytic domain with pK(a) and dicarboxylic acid
      structure properties that hydrolyze cellulose while producing minimal degradation
      of the glucose formed. In this study we report results of a rapid chromatographic
      method to assess the binding characteristics of potential cellulose binding
      domains for the construction of a synthetic cellulase over a wide range of
      temperatures (20 degrees to 120 degrees C). Aromatic, planar chemical structures
      appear to be key indicators of cellulose adsorption. Indole, the side-chain of
      the amino acid tryptophan, has been shown to reversibly adsorb to cellulose at
      temperatures between 30 degrees and 120 degrees C. Trypan blue, a polyaromatic,
      planar molecule, was shown to be irreversibly adsorbed to cotton cellulose at
      temperatures of <120 degrees C on the time scale of the experiments. These
      results confirm the importance of hydrophobic cellulose and the cellulose-binding
      component of cellulolytic enzymes and cellulolytic enzyme mimetics.

PMID- 15162452
TI  - Insights into adenoviral vector production kinetics in acoustic filter-based
      perfusion cultures.
AB  - One of the major limitations in the production of adenoviral vectors is the
      reduction in cell-specific productivity observed for increasing cell density at
      infection in batch cultures. This observation strongly suggests some nutrient
      depletion and/or metabolite inhibition in the media. These limitations have been
      partially overcome through other feeding strategies, such as fed-batch and
      sequential batch operations. To improve these results, we evaluated perfusion as
      a strategy to increase the volumetric productivity of HEK-293 cell cultures, by
      allowing productive infection at higher cell densities. An acoustic cell
      separator was employed in consideration of the increased shear sensitivity of the
      cells during the infection phase. The effects of perfusion rate and cell density
      at infection on the production of a recombinant adenovirus expressing the GFP
      were investigated. The perfusion mode allowed successful infection at cell
      densities in the range of 2.4-3 x 10(6) cell/mL, while maintaining a similar cell
      specific productivity (17,900 +/- 2400 VP/cell) to that of a batch infected at a
      low cell density (5 x 10(5) cell/mL). The highest virus concentrations (4.1 +/-
      0.6 x 10(10) VP/mL) were attained for a feed rate of 2 vol/d and constituted a
      fivefold increase compared to a batch with medium replacement. Rapid assessment
      of the infection status was achieved through the use of on-line monitoring of
      respiration, fluorescence, and biovolume. Analysis of the kinetics of nutrient
      consumption and metabolite production revealed that a reduction in specific
      productivity is correlated with reduced metabolic activity.

PMID- 15162453
TI  - Method for determining oxygen consumption rates of static cultures from
      microplate measurements of pericellular dissolved oxygen concentration.
AB  - We describe a simple protocol for determining the oxygen consumption of cells in
      static culture. The protocol is based on a noninvasive oxygen-sensing microplate
      and a simple mathematical model derived from Fick's Law. The applicability of the
      model is confirmed by showing the correlation of computed oxygen consumption rate
      (OCR) values to actual cell densities ascertained by direct cell counting and/or
      MTT for HL60 and U937 cells cultured in suspension. Correlation between computed
      OCR and these other indications of cell number was quite good, as long as the
      cultures were not diffusion-limited for oxygen. The impact of the geometric
      factors of media depth and well size were confirmed to be consistent with the
      model. Based on this demonstrated correlation, we also developed a simple,
      completely noninvasive algorithm for ascertaining the per-cell oxygen utilization
      rate (OUR), which is the ratio of OCR to cell number, and a fundamental cell
      characteristic. This is accomplished by correlating the known seed densities to
      extrapolated determinations of OCR at time zero. Such determinations were
      performed for numerous cell types, in varying well sizes. Resulting OUR values
      are consistent with literature values acquired by far more painstaking methods,
      and ranged from <0.01 fmol.min(-1).cell(-1) for bacteria to 0.1-10 fmol.min(
      1).cell(-1) for immortalized mammalian and insect cell lines to >10 fmol.min(
      1).cell(-1) for primary hepatocytes. This protocol for determining OCR and OUR is
      extremely simple and broadly applicable and can afford rapid, informative, and
      noninvasive insight into the state of the culture.

PMID- 15162454
TI  - Biphasic aqueous/organic biotransformation of acetaldehyde and benzaldehyde by
      Zymomonas mobilis pyruvate decarboxylase.
AB  - Zymomonas mobilis pyruvate decarboxylase (PDC) transformed acetaldehyde and
      benzaldehyde into (R)-phenylacetylcarbinol (PAC), the precursor for the synthesis
      of ephedrine and pseudoephedrine. Organic solvents were screened for a biphasic
      biotransformation with the enzyme in an aqueous phase and the toxic substrates
      delivered through the organic phase. In the absence of substrates a second phase
      of 1-pentanol, hexadecane or MTBE (methyl tertiary-butyl ether) stabilized the
      PDC activity in comparison to a control without added solvent. Organic phase
      solvents for optimal PAC production had partitioning coefficient (log P) values
      between 0.8 and 2.8 (production of more than 8 mg PAC/ U PDC), however there was
      no correlation between enzyme stability and log P. Best PAC formation was
      observed with the eight tested alcohols, which in contrast to the other solvents
      allowed lower initial concentrations of toxic acetaldehyde (54-81 mM) in the
      aqueous phase. 1-pentanol, 1-hexanol, and isobutanol resulted in the highest
      specific PAC production of 11 mg PAC /U PDC. Without the addition of an organic
      phase, only 1.2 mg/U was formed.

PMID- 15162455
TI  - In situ product removal using a crystallization loop in asymmetric reduction of 4
      oxoisophorone by Saccharomyces cerevisiae.
AB  - In situ product crystallization was investigated for solid product crystals that
      were obtained during fermentation. The model reaction was the asymmetric
      reduction of 4-oxoisophorone (OIP) using baker's yeast (S. cerevisiae) as a
      biocatalyst. The target product was 6R-dihydro-oxoisophorone (DOIP), also known
      as levodione, a key intermediate in carotenoid synthesis. DOIP was degraded by
      baker's yeast mainly to (4S,6R)-actinol, an unwanted byproduct in the process.
      Actinol formation reached up to 12.5% of the initial amount of OIP in the reactor
      during a batch process. However, better results were obtained when the dissolved
      DOIP concentration was controlled using an integrated fermentation
      crystallization process because: (a) actinol formation was reduced to 4%; and (b)
      DOIP crystal formation in the reactor was avoided. DOIP productivity was improved
      by 50% and its selectivity was raised from 87% to 96% relative to the batch
      process. In the integrated process, most of the product was recovered as pure
      crystals; this may already minimize, if not eliminate, the need for organic
      solvents in the final purification steps. An almost sixfold reduction in
      biocatalyst consumption per kilogram product was achieved, which also can
      contribute to the minimization of waste streams.

PMID- 15162456
TI  - Effect of ethanol, acetate, and phenol on toluene degradation activity and tod
      lux expression in Pseudomonas putida TOD102: evaluation of the metabolic flux
      dilution model.
AB  - The reporter strain Pseudomonas putida TOD102 (with a tod-lux fusion) was used in
      chemostat experiments with binary substrate mixtures to investigate the effect of
      potentially occurring cosubstrates on toluene degradation activity. Although
      toluene was simultaneously utilized with other cosubstrates, its metabolic flux
      (defined as the toluene utilization rate per cell) decreased with increasing
      influent concentrations of ethanol, acetate, or phenol. Three inhibitory
      mechanisms were considered to explain these trends: (1) repression of the tod
      gene (coding for toluene dioxygenase) by acetate and ethanol, which was
      quantified by a decrease in specific bioluminescence; (2) competitive inhibition
      of toluene dioxygenase by phenol; and (3) metabolic flux dilution (MFD) by all
      three cosubstrates. Based on experimental observations, MFD was modeled without
      any fitting parameters by assuming that the metabolic flux of a substrate in a
      mixture is proportional to its relative availability (expressed as a fraction of
      the influent total organic carbon). Thus, increasing concentrations of
      alternative carbon sources "dilute" the metabolic flux of toluene without
      necessarily repressing tod, as observed with phenol (a known tod inducer). For
      all cosubstrates, the MFD model slightly overpredicted the measured toluene
      metabolic flux. Incorporating catabolite repression (for experiments with acetate
      or ethanol) or competitive inhibition (for experiments with phenol) with
      independently obtained parameters resulted in more accurate fits of the observed
      decrease in toluene metabolic flux with increasing cosubstrate concentration.
      These results imply that alternative carbon sources (including inducers) are
      likely to hinder toluene utilization per unit cell, and that these effects can be
      accurately predicted with simple mathematical models.

PMID- 15162457
TI  - Novel chemically synthesized hydroxyl-containing jasmonates as powerful inducing
      signals for plant secondary metabolism.
AB  - Novel hydroxyl-containing jasmonate derivatives were chemically synthesized and
      evaluated by bioassay as potential elicitors for stimulating the biosynthesis of
      plant secondary metabolites. A suspension culture of Taxus chinensis, which
      produces a bioactive taxoid, taxuyunnanine C (Tc), was taken as a model plant
      cell system. Experiments on the timing of addition of jasmonates and dose
      response indicated that day 7 and 100 microM was the optimal elicitation time and
      concentration, respectively, for both cell growth and Tc accumulation. Tc
      accumulation was increased more in the presence of novel hydroxyl-containing
      jasmonates compared to that with methyljasmonate (MJA) addition. For example,
      addition of 100 microM 2,3-dihydroxypropyl jasmonate on day 7 led to a very high
      Tc content of 47.2 +/- 0.5 mg/g (at day 21), whereas the Tc content was 29.2 +/-
      0.6 mg/g (on the same day) with addition of 100 microM MJA. Quantitative
      structure-activity analysis of various jasmonates suggests that the optimal
      lipophilicity and the number of hydroxyl groups may be two important factors
      affecting their elicitation activity. In addition, the jasmonate elicitors were
      found to induce plant defense responses, including oxidative burst and activation
      of L-phenylalanine ammonia lyase (PAL). Interestingly, a higher level of H(2)O(2)
      production and PAL activity was detected with elicitation by the synthesized
      jasmonates compared with that by MJA, which corresponded well to the superior
      stimulating activity in the former. This work indicates that the newly
      synthesized hydroxyl-containing jasmonates can act as powerful inducing signals
      for secondary metabolite biosynthesis in plant cell cultures.

PMID- 15162458
TI  - Preparation of single cells from aggregated Taxus suspension cultures for
      population analysis.
AB  - A method for the isolation of single plant cells from Taxus suspension cultures
      has been developed for the analysis of single cells via rapid throughput
      techniques such as flow cytometry. Several cell wall specific enzymes, such as
      pectinase, pectolyase Y-23, macerozyme, Driselase(R), and cellulase were tested
      for efficacy in producing single cell suspensions. The method was optimized for
      single cell yield, viability, time, and representivity of aggregated cell
      cultures. The best combination for single cell isolation was found to be 0.5%
      (w/v) pectolyase Y-23 and 0.04% (w/v) cellulase. High viability (>95%) and high
      yields of single cell aggregates (>90%) were obtained following 4 hours of
      digestion for four separate Taxus cell lines. In addition, methyl jasmonate
      elicitation (200 microM) was found to have no effect on three of the four tested
      Taxus lines. Isolated single cells were statistically similar to untreated cell
      cultures for peroxidase activity (model cell wall protein) and paclitaxel content
      (secondary metabolite produced in Taxus cell cultures). In comparison,
      protoplasts showed marked changes in both peroxidase activity and paclitaxel
      content as compared to untreated cultures. The use of flow cytometry was
      demonstrated with isolated cells that were found to have > 99% viability upon
      staining with fluorescein diacetate. The development of a method for the
      isolation of single plant cells will allow the study of population dynamics and
      culture variability on a single cell level for the development of population
      models of plant cell cultures and secondary metabolism.

PMID- 15162459
TI  - Kinetic analysis and modeling of firefly luciferase as a quantitative reporter
      gene in live mammalian cells.
AB  - Firefly luciferase has proven to be a highly sensitive and quantitative reporter
      gene for studying gene delivery and regulation, and its recent use in live cells
      and organisms promises to further expand its utility. However, the intracellular
      behavior and properties of the enzyme are not well characterized. Specifically,
      information on the intracellular kinetics and stability of luciferase activity is
      necessary for real-time luminescence counts from live cells to be quantitatively
      meaningful. Here, we report a dynamic analysis of luciferase activity in the
      context of living mammalian cells. We have determined the relative light units
      measured in living cells to be proportional to that found in cell lysate. We have
      also calculated the K(m) of luciferase in living cells to be approximately 1 mM,
      a value much higher than the 10 microM found for pure enzyme in vitro. In
      addition, a 2-hour half-life of luciferase activity in live cells was measured in
      real time. Finally, we have modeled luciferase activity in live cells for the
      purposes of understanding and translating the luciferase signal into a more
      effective metric of gene expression and cell behavior.

PMID- 15162460
TI  - In vitro and in vivo enzyme studies of polyhemoglobin-tyrosinase.
AB  - Melanoma is now the fifth most common type of cancer in North America. At
      present, there is no optimal treatment for this cancer. However, the lowering of
      the tyrosine level can inhibit the growth of melanoma. Unfortunately, this diet
      restriction cannot be humanly tolerated and causes vomiting, nausea, and severe
      body weight loss. To prevent these problems, we are studying a new approach
      involving the preparation intermolecularly crosslinked hemoglobin and tyrosinase
      for intravenous injection. In this article we describe the method of preparation
      and the structural and functional properties of polyhemoglobin-tyrosinase. We
      evaluate the effects of varying glutaraldehyde ratio, crosslinking time, and
      enzyme concentration on the enzyme activity of polyhemoglobin-tyrosinase. We also
      optimize the molecular weight distribution of polyhemoglobin-tyrosinase. The
      stability of polyhemoglobin-tyrosinase at 37 degrees C is much more stable when
      compared to noncrosslinked tyrosinase solution. Animal studies show that a higher
      degree of polymerization correlates with a longer circulation time of
      polyhemoglobin-tyrosinase, and the optimal crosslinking time is 24 hours. One
      intravenous injection of polyhemoglobin-tyrosinase lowers the plasma tyrosine to
      about 10% of its original level within one hour.

PMID- 15162461
TI  - Glutamic acid removal and PHB storage in the activated sludge process under
      dynamic conditions.
AB  - Glutamic acid removal in the activated sludge process is studied herein,
      primarily the formation of storage polymers under dynamic conditions. The
      activated sludge process was operated by using a sequencing batch reactor (sludge
      age of 6 d) fed with a synthetic mixture of readily available carbon sources,
      including glutamic acid. Removal of glutamic acid as the only carbon sources was
      studied in batch tests, along with oxygen consumption, ammonia uptake-release,
      and formation of storage polymers. It was found that poly-3-hydroxybutyrate (PHB)
      was stored and that the storage also occurred simultaneously to biomass growth.
      PHB storage accounted for 16% of the overall solids that were formed from
      glutamic acid, as the average value of nine batch tests. Neither other
      Polyhydroxyalkanoates nor polyglutamic acid were detected. Nuclear magnetic
      resonance analysis, performed on biomass extracts, allowed us to clarify the main
      metabolic pathways involved in glutamic acid removal and, in particular, the
      pathways involved in PHB storage. It was found that glutamic acid enters the
      Krebs cycle as alpha-ketoglutaric acid and exits to form pyruvic acid and then
      acetyl-CoA, which is the starting point of PHB production pathway.

PMID- 15162462
TI  - On-line monitoring of human prostate cancer cells in a perfusion rotating wall
      vessel by near-infrared spectroscopy.
AB  - PC-3 human prostate cancer cells have been cultivated in a rotating wall vessel
      in which glucose, lactate, and glutamine profiles were monitored noninvasively
      and in real time by near-infrared (NIR) spectroscopy. The calibration models were
      based on off-line spectra from tissue culture experiments described previously
      (Rhiel et al., Biotechnol Bioeng 77:73-82). Monitoring performance was improved
      by Fourier filtering of the spectra and initial off-set adjustment. The resulting
      standard errors of predictions were 0.95, 0.74, and 0.39 mM for glucose, lactate,
      and glutamine, respectively. The concentration of ammonia could not be accurately
      measured from the same spectra. In addition, metabolite uptake and production
      rates were determined for PC-3 prostate cancer cells during exponential growth in
      batch-mode cultivation. Cells grew with a doubling time of 21 h and consumed
      glucose and glutamine at rates of 6.8 and 1.8 x 10(-17) mol/cell.s, respectively.
      This resulted in lactate and ammonia production rates of 11.9 and 1.3 x 10(-17)
      mol/cell.s, respectively. Compared with other monitoring technologies, this
      technology has many advantages for spaceflights and stand-alone units; for
      instance, calibration can be performed at one time and then applied in a
      reagentless, low-maintenance way at a later time. The resulting concentration
      information can be incorporated into closed-loop control schemes, thereby leading
      to better in vitro models of in vivo behavior.

PMID- 15162463
TI  - Advances in adult living donor liver transplantation: a review based on reports
      from the 10th anniversary of the adult-to-adult living donor liver
      transplantation meeting in Tokyo.
AB  - In 1993, the Shinshu Group performed the first successful adult-to-adult living
      donor liver transplantation (LDLT). During the first 10 years of LDLT, many
      technical innovations have been reported. The major limitation of LDLT for adult
      recipients is the size of the graft. To overcome the problem, several graft types
      were designed, including left liver graft with caudate lobe, right liver,
      modified right liver, and right lateral sector and dual grafts. The necessity and
      criteria of reconstruction of middle hepatic vein is still on debate in right
      liver graft without trunk of middle hepatic vein. Biliary reconstruction remains
      a significant source of morbidity in LDLT. Donor safety must always be the
      primary consideration in LDLT and the selection criteria and management of the
      living donor must continue to be refined. On February 21, 2004, the 10(th)
      anniversary of the adult-to-adult LDLT meeting was held in Tokyo to review the
      accumulated experience and the presented information is summarized.

PMID- 15162464
TI  - The effect of donor weight reduction on hepatic steatosis for living donor liver
      transplantation.
AB  - Hepatic steatosis is often associated with overweight, so we tried body-weight
      reduction in potential living donors with fatty liver and/or obesity to alleviate
      hepatic steatosis. We advised to reducing the body weight by 5% for 9 potential
      living donors showing hepatic steatosis of 25-95% on initial percutaneous needle
      biopsy (PCNB). They lost 5.9 +/- 2.0% of the initial body weight during 2-6
      months and their body mass index changed from 25.3 +/- 3.8 to 23.7 +/- 3.4. Total
      amount of hepatic steatosis changed significantly from 48.9 +/- 25.6% to 20.0 +/-
      16.2% before and after weight reduction. The proportional reduction in
      microvesicular steatosis was more obvious than in macrovesicular fatty changes.
      Six right lobe and 3 left lobe grafts were procured uneventfully from these 9
      donors. All donors recovered uneventfully, and all 9 recipients survived more
      than 15 months to date. In conclusion, we think that short-term weight reduction
      of living donors will be helpful to alleviate excessive hepatic steatosis,
      especially in microvesicular type and can contribute to expand the pool of
      marginal living donors.

PMID- 15162465
TI  - Obesity in potential living donors: success with simplicity.

PMID- 15162466
TI  - Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction
      therapy after liver transplantation: a protocol with early elimination of
      steroids and reduction of tacrolimus dosage.
AB  - A prospective evaluation was performed to study the potential benefits of the use
      of interleukin-2 receptor antibody (IL-2Rab) in the induction therapy with early
      elimination of steroid and reduction of tacrolimus dosage in liver transplant
      recipients among whom 94% had chronic hepatitis B infection. Thirty-one liver
      transplant recipients who underwent right-lobe live donor (n = 19) or cadaveric
      (n = 12) liver transplantation received IL-2Rab, basiliximab 20 mg intravenously
      within 6 hours of graft reperfusion and on postoperative day 4 (IL-2ab group).
      Two doses of steroid injection were given intraoperatively and on postoperative
      day 1. Postoperative immunosuppression was maintained with oral tacrolimus and
      mycophenolate mofetil without the use of steroids. The operative outcomes were
      compared with those of 49 patients who received standard immunosuppressive
      regimen consisting of tacrolimus and corticosteroid (steroid group). The overall
      postoperative morbidity and hospital stay were comparable between the 2 groups.
      There were significantly lower incidences of postoperative new-onset diabetes (0%
      vs 28%, P =.011), acute cellular rejection (6% vs 27%, P =.038), and
      cytomegalovirus (CMV) antigenemia (0% vs 18%, P =.011) in the IL-2Rab group
      compared with the steroid group. The blood cholesterol level at 6 months after
      transplantation was significantly lower in the IL-2Rab group (median, 4.0 vs 4.4
      mmol/L, P =.007). On follow-up, none of the patients in the IL-2Rab group had
      hepatitis B viral breakthrough or hepatocellular carcinoma (HCC) recurrence,
      whereas 1 and 3 patients in the steroid group developed these complications,
      respectively. In conclusion, treatment of liver transplant recipients with IL
      2Rab with early withdrawal of steroids and reduction of tacrolimus dosage is
      associated with lower incidences of postoperative new-onset diabetes, acute
      cellular rejection, and CMV antigenemia, as well as a lower serum cholesterol
      level. Further studies and long-term follow-up are required to document their
      potential benefits on hepatitis B and HCC recurrences.

PMID- 15162467
TI  - Cytotoxic T-cell elimination during anti-CD4-induced rat liver acceptance and
      rapid replacement of functional graft antigen-presenting cells.
AB  - In previous studies, we showed that primed T cells were eliminated in long-term
      survival Wistar Furth (WF) recipient rats with spontaneously accepted Lewis (LEW)
      liver graft and that the grafted liver lost the ability to elicit rejection
      reaction early after liver transplantation. We hypothesized that the same
      phenomenon may be observed in tolerant animals after immunosuppression in a
      rejector rat strain combination (WF-->LEW). Furthermore, we proposed the
      repopulation of liver allograft with host antigen-presenting cells rapidly after
      transplantation. Recipient LEW rats that underwent anti-CD4 therapy accepted the
      WF liver allografts after a transient rejection reaction. In tolerant animals,
      alloreactive CD8 T cell precursors were present, but primed T cells were absent.
      Intraperitoneal challenge with grafted WF liver homogenates obtained from
      recipient LEW rats on day 4 after transplantation did not induce transient
      rejection responses in long-term survival recipient LEW rats, a finding that
      differed from the results of experiments using normal WF liver homogenates.
      However, challenge with grafted WF liver homogenates, similar to those of normal
      LEW liver homogenates, induced rejection responses in long-term survival
      recipient WF rats with LEW liver allograft. Flow cytometric analysis confirmed
      that most of nonparenchymal cells in the grafted WF liver were recipient (LEW)
      genotype. These observations showed that the deletional mechanism of effector T
      cells also is observed in this setting, and professional donor antigen-presenting
      cells are replaced by those of recipient genotype within the graft during the
      early phase of transplantation.

PMID- 15162468
TI  - Significant enhancement by anti-ICOS antibody of suboptimal tacrolimus
      immunosuppression in rat liver transplantation.
AB  - A member of the costimulatory molecule family, inducible costimulator (ICOS), is
      expressed on activated T cells and plays a critical role in their primary
      activation and cytokine production. ICOS is involved in different immune
      phenomena, such as Th1-mediated autoimmune disease and graft rejection. Although
      blockade of ICOS costimulation theoretically may protect grafts from rejection, a
      single dose of anti-ICOS antibody did not result in the prolongation of rat liver
      allograft survival. However, in this article, we report that anti-rat ICOS
      antibody markedly enhanced the immunosuppressive activity of a suboptimal dose of
      tacrolimus (FK506). After fully allogenic DA to LEW liver transplantation,
      recipients received a single injection of tacrolimus (1 mg/kg, intramuscularly)
      with or without anti-ICOS antibody (1 mg/kg, intravenously). Recipient survival
      was significantly prolonged in rats treated with both the antibody and suboptimal
      tacrolimus (median survival time 44 days vs. 28 days with tacrolimus alone, P
      <.01). The extent of cell infiltration into the graft was closely associated with
      prolongation of recipient survival. Our findings thus demonstrate that anti-ICOS
      antibody immunotherapy combined with suboptimal tacrolimus has a synergistic
      effect in preventing hepatic allograft rejection and that it may induce long-term
      graft acceptance intimately associated with a marked reduction of intragraft T
      lymphocyte infiltration.

PMID- 15162469
TI  - Enhanced proliferation of hepatic progenitor cells in rats after portal branch
      occlusion.
AB  - It is known that hepatic progenitor cells increase in number after liver injury
      caused by carcinogens, but this injury cannot be reproduced in humans. In order
      to create a practical source of hepatic progenitor cells, changes in the number
      of liver epithelial cells (LECs), a type of hepatic progenitor cell, were
      examined following partial interruption of the portal flow. Efficiency in this
      isolation procedure was investigated, and isolated LECs were transplanted into
      livers to demonstrate their differentiation into hepatocytes in vivo.A volume of
      70% of Sprague-Dawley rat's livers was exposed to portal vein ligation. LECs,
      identified as alpha-fetoprotein (AFP)-positive and albumin-negative cells, were
      counted and LECs isolated from the portal vein ligated-lobe were characterized by
      immunostaining and Western blotting. Isolated cells were subjected to a 1-week
      culture, and the number of colonies formed on dishes was counted. The cells were
      then transplanted to the livers of genetic analbuminemic rats and identified by
      immunohistochemistry. The number of LECs in the portal ligated-lobes on day 7 was
      14.7 +/- 6.5 cells/1,000 hepatocytes: 18 times higher than numbers in a normal
      liver. A significant increase was noted from day 3 until day 28. Isolated LECs
      were AFP-positive, albumin-negative, and cytokeratin-19-positive cells. The
      number of colonies on the 7th day following portal vein ligation was 42 times
      higher than in a normal liver. After transplantation of the LECs to the
      analbuminemic rat, a cluster of albumin-producing cells was present until day 56,
      suggesting that they differentiate into hepatocytes. We conclude that after
      portal vein occlusion, the liver can be a good source of hepatic progenitor cell.
      These results open up the possibility of cellular transplantation for liver
      functional support in clinical settings.

PMID- 15162470
TI  - Tailoring donor hepatectomy per segment 4 venous drainage in right lobe live
      donor liver transplantation.
AB  - Including the middle hepatic vein (MHV) in the right lobe liver graft for adult
      to-adult live donor liver transplantation provides more functional liver by
      securing adequate venous drainage. Donor outcome of this procedure in relation to
      different venous drainage patterns of segment 4 is unknown. Modification of graft
      harvesting technique by preserving segment 4b hepatic vein (V4b) in theory
      compensates for unfavorable venous drainage patterns. Consecutive 120 right lobe
      live donors were included. Computed tomography was studied in detail to assign
      each donor to one of the three types of the Nakamura classification of venous
      drainage pattern of segment 4. Type I drainage was mainly via the left hepatic
      vein (LHV), type II drainage was equally into the MHV and LHV, and type III
      drainage was predominantly into the MHV. Any distinct umbilical vein was also
      noted. In the early part of the series, the V4b draining into the MHV was divided
      to provide a long MHV stump in the graft. In the later part of the series,
      prominent V4b draining into the MHV was preserved in the donor as far as
      possible. Donor outcomes were measured by peak values of prothrombin time (PT),
      serum bilirubin and transaminases levels. There was no donor mortality. Type I
      donors (n=69) had the best outcome with peak PT of 17.9 sec (range 12.3-23.3
      sec). Type II donors (n=44) had peak PT of 18.5 sec (range 15.4-24.4 sec). When
      V4b was preserved in type II donors (n=19), the peak PT (18.0 sec, range 15.4
      20.7 sec) became significantly lower than that of type II donors who had V4b
      sacrificed (20.3 sec, range 16.2-24.4 sec) (P=0.001). A distinct umbilical vein
      (n=91, 75.8%) was insignificant for donor outcome measured by peak PT.
      Multivariate analysis identified that type II donors with V4b sacrificed (n=25),
      type III donors (n=7), and the first 50 cases had less favorable outcomes. In
      conclusion, unfavorable venous drainage patterns were one of the independent
      factors compromising postoperative donor liver function, but was circumvented by
      preservation of V4b.

PMID- 15162471
TI  - Hepatic venous congestion in living donor liver transplantation: preoperative
      quantitative prediction and follow-up using computed tomography.
AB  - Hepatic venous congestion (HVC) has not been assessed quantitatively prior to
      hepatectomy and its resolving mechanism has not been fully analyzed. We devised
      and verified a new method to predict HVC, in which HVC was estimated from
      delineation of middle hepatic vein (MHV) tributaries in computed tomography (CT)
      images. The predicted HVC was transferred to the right hepatic lobes of 20 living
      donors using a paper scale, and it was compared with the actual observed HVC that
      occurred after parenchymal transection and arterial clamping. The evolution of
      HVC from its emergence to resolution was followed up with CT. Volume proportions
      of the predicted and observed HVC were 31.7 +/- 6.3% and 31.3 +/- 9.4% of right
      lobe volume (RLV) (P =.74), respectively, which resulted in a prediction error of
      3.8 +/- 3.7% of RLV. We observed the changes in the HVC area of the right lobes
      both in donors without MHV trunk and in recipients with MHV reconstruction. After
      7 days, the HVC of 33.5 +/- 7.7% of RLV was changed to a computed tomography
      attenuation abnormality (CTAA) of 28.4 +/- 5.3% of RLV in 12 donor remnant right
      lobes, and the HVC of 29.1 +/- 11.5% of RLV was reduced to a CTAA of 9.3 +/- 3.2%
      of RLV in 7 recipient right lobe grafts with MHV reconstruction. There was no
      parenchymal regeneration of the HVC area in donor remnant livers during first 7
      days. In conclusion, we believe that this CT-based method for HVC prediction
      deserves to be applied as an inevitable part of preoperative donor evaluation.
      The changes in CTAA observed in the right lobes of donors and recipients indicate
      that MHV reconstruction can effectively decrease the HVC area.

PMID- 15162472
TI  - Pringle's maneuver and selective inflow occlusion in living donor liver
      hepatectomy.
AB  - While inflow occlusion techniques such as Pringle's maneuver are accepted methods
      of reducing bleeding without inducing liver injury during liver surgery, donor
      hepatectomy for living donor liver transplantation is currently performed without
      inflow occlusion for fear that injury to the graft may result. We have performed
      donor hepatectomy for 12 years using selective intermittent inflow occlusion, a
      technique in which the portion used to form the graft is perfused during
      hepatectomy. Starting in November 2000, we applied intermittent Pringle's
      maneuver to donor hepatectomy in 81 cases of living donor liver transplantation.
      We reviewed our experience with Pringle's maneuver and selective inflow occlusion
      techniques in donor hepatectomy in living donor liver transplantation. The
      quality of the grafts was assessed and compared by determining maximum
      postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      values. Neither primary nonfunction nor dysfunction occurred. Maximum AST values
      in the recipients were the same whether the liver segments that formed the grafts
      were totally ischemic during dissection (total ischemia), partially ischemic
      (partial ischemia), perfused only with arterial blood flow (portal ischemia), or
      not ischemic at all (no ischemia). Maximum ALT values in the recipients of the
      total ischemia group was lower, albeit not significantly, than in other groups.
      Total inflow occlusion can be applied to living donor hepatectomy without causing
      graft injury. In conclusion, because the transection surface is blood-free, there
      is decreased risk to the donor during living donor liver transplantation surgery,
      and surgeons should not hesitate to apply this technique because it contributes
      to donor safety.

PMID- 15162473
TI  - Estimation of standard liver volume for liver transplantation in the Korean
      population.
AB  - The standard liver volume (LV) of a recipient is estimated in liver
      transplantation to determine the minimum LV necessary for the recipient. Simple
      linear formulas of LV estimation were developed for the Japanese and Caucasian
      populations. The present study examined the applicability of the reported
      formulas to the Korean population. Liver density (LD) was determined by analyzing
      24 healthy livers. Data of liver weight (LW), body weight (BW), body height (BH),
      body surface area (BSA), and age were obtained from 652 postmortem examination
      reports (age, 42.4 +/- 16.5 years) showing normal livers. The LV of each subject
      was estimated by LW / LD and the relationships between LV, BW, BSA, and age were
      analyzed. LD was 1.04 +/- 0.07 kg/L. LV / BW decreased as age increased in the
      children but leveled off in the adults; the rate of increase in LV along with BSA
      in individuals with BSA <1.2 m(2) appeared less than the corresponding rate in
      individuals with BSA >/=1.2 m(2). The Japanese formula produced underestimates
      for the Korean population (226.9 +/- 289.4 mL), while the Caucasian formula
      produced random errors (-30.64 +/- 281.5 mL). A better LV estimation formula was
      established: LV (mL) = 21.585 x BW (kg)(0.732) x BH (cm)(0.225) (adjusted R(2) =
      0.59; SE = 275.8 mL). In conclusion, this study indicates that a nonlinear or
      piecewise linear model is more desirable than a simple linear model for LV
      estimation in children and adults, because LV / BW and LV / BSA are not constant
      with age and BSA.

PMID- 15162474
TI  - Heme oxygenase-1 potentiates the survival of small-for-size liver graft.
AB  - This study aims to clarify the role of heme oxygenase-1 (HO-1) in small-for-size
      liver transplantation. Transplantation was performed using 40% small-for-size or
      100% whole liver grafts in rats. When no treatment was given, over-expression of
      HO-1 was detected predominantly in the small-for-size grafts at 6 hours after
      reperfusion as compared to whole grafts in both syngeneic and allogeneic
      combinations. Recombinant adenoviral vector encoding HO-1 gene (AdHO-1)
      administered to donors 48 hours before transplantation enhanced HO-1 expression
      in both whole and small-for-size allografts, with a predominant augmentation in
      the small-for-size allografts, suggesting favorable conditions for the induction
      of HO-1 expression in small-for-size allografts. In close relation to the
      expression level of HO-1, AdHO-1 significantly prolonged both whole and small-for
      size allograft survivals, with a remarkable effect in the small-for-size
      allograft group. The prolongation of allograft survival was blocked by the HO-1
      inhibitor (zinc protoprophyrin IX). The non-treated small-for-size allografts
      demonstrated impaired liver function during the early period after reperfusion,
      which could be improved by over-expression of HO-1, but reversed by the HO-1
      inhibitor. The markedly increase expression HO-1 in small-for-size allografts was
      associated with lower levels of adhesion molecules and pro-inflammatory cytokines
      in the early phase after reperfusion. These findings support the beneficial
      effects of HO-1 on allograft survival. In conclusion, the ability of small-for
      size grafts in the induction of HO-1 expression might facilitate their own
      survival in liver transplantation.

PMID- 15162475
TI  - Optimal cycle of intermittent portal triad clamping during liver resection in the
      murine liver.
AB  - We designed this experimental study to determine the optimal cycle for
      intermittent inflow occlusion during liver resection. A cycle of intermittent
      clamping (IC) for 15 minutes of ischemia followed by reperfusion for 5 minutes
      during liver resection is currently the most popular protocol used by experienced
      liver centers. As each period of reperfusion is associated with bleeding, longer
      periods of clamping would be advantageous. However, the longest safe duration of
      successive ischemia is unknown. Three groups of mice were subjected to a total
      liver ischemic period for 90 minutes; 2 groups underwent IC for 15 or 30 minutes,
      respectively, followed by 5 minutes of reperfusion, while the control group was
      subjected to continuous inflow occlusion only. The degree of tissue injury was
      assessed using biochemical and histological markers, as well as animal survival.
      While serious injury was observed in the continuous clamping group, both IC
      groups were associated with minimal injury, including lesser degrees of apoptosis
      and necrosis. All animals survived in the IC groups, while all animals died
      following 90 minutes of continuous inflow occlusion. In conclusion, intermittent
      portal pedicle clamping with 15- or 30-minute cycles is highly protective. A
      period of 30 minutes clamping should be preferred, since this would decrease the
      amount of blood loss associated with each cycle. This data should be confirmed in
      humans, and may represent a change in the current practice of hepatic surgery.

PMID- 15162476
TI  - Umbilical portion of recipient's left portal vein: a useful vascular conduit in
      dual living donor liver transplantation for the thrombosed portal vein.
AB  - We considered performing living donor liver transplantation (LDLT) in a larger
      size recipient. When the recipient was large-sized, or when the donor liver was
      severely steatotic or had a right-to-left volume discrepancy. We devised dual
      living donor liver transplantation (DLDLT) to make up for graft size
      insufficiency and to secure the donor's safety. However, portal vein thrombosis
      (PVT) presented a challenge for DLDLT because of the need for intact right and
      left portal veins for the implantation of both liver grafts. Our 52-year-old male
      patient with hepatitis B cirrhosis had suffered from repeated esophageal and
      gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic
      portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the
      area just above the spleno-mesenteric confluence to the right and left PV. Also,
      the right PV orifice was destructed and difficult to isolate because of severe
      periportal inflammation and neointima growth in the TIPS mesh. The patient's two
      sons were inadequate for donation because of right-to-left volume discrepancy.
      Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size
      insufficiency and to secure donor safety, and we substituted an intact umbilical
      portion of recipient's left PV for the destroyed right PV. The patient recovered
      well, and liver function has been normal for more than a year. In conclusion, the
      umbilical portion of recipient's left PV can be a useful vascular substitute for
      the reconstruction of a thrombosed main portal branch in DLDLT.

PMID- 15162477
TI  - End-to-side portocaval shunting for a small-for-size graft in living donor liver
      transplantation.
AB  - In the development of adult-to-adult living donor liver transplantation (LDLT),
      the small-for-size graft has been associated with poor clinical outcome.
      Persistent portal hypertension or portal venous overperfusion are considered to
      be causative factors, and partial diversion of portal flow to systemic
      circulation may be effective for avoiding injuries that occur in the small-for
      size (SFS) graft. Recently, we constructed an end-to-side portocaval shunting
      using 1 of the portal branches and anastomosed the other branch with the portal
      vein of the graft in 2 cases of LDLT recipients transplanted with a SFS graft.
      With the suppression of portal hypertension, as well as sufficient portal flow to
      the graft, the recipients recovered successfully with favorable graft function.
      This new and simple technique may be able to be used as a feasible and effective
      method to attenuate the SFS syndrome.

PMID- 15162479
TI  - Resection prior to liver transplantation for hepatocellular carcinoma: a strategy
      of optimizing the role of resection and transplantation in cirrhotic patients
      with preserved liver function.

PMID- 15162478
TI  - The right may not be always right: biliary anatomy contraindicates right lobe
      live donor liver transplantation.

PMID- 15162481
TI  - Designing proteins from the inside out.
AB  - Globular proteins are characterized by the specific and tight packing of
      hydrophobic side-chains in the so-called "hydrophobic core." Formation of the
      core is key in folding, stabilization, and conformational specificity. The
      critical role of hydrophobic cores in maintaining the highly ordered structures
      present in natural proteins justifies the tremendous efforts devoted to their
      redesign. Both experimental and computational combinatorial-based approaches have
      been reported in the last years as powerful protein design tools. These manage to
      explore large regions of the sequence/conformational space, allowing the search
      for alternative protein core arrangements displaying native-like properties. The
      overall results obtained from core design projects have contributed significantly
      to our present knowledge of protein folding and function. In addition, core
      design has worked as a benchmark for the development of ambitious protein design
      projects that nowadays are allowing the de novo design of novel protein
      structures and functions.

PMID- 15162482
TI  - Prediction of transmembrane regions of beta-barrel proteins using ANN- and SVM
      based methods.
AB  - This article describes a method developed for predicting transmembrane beta
      barrel regions in membrane proteins using machine learning techniques: artificial
      neural network (ANN) and support vector machine (SVM). The ANN used in this study
      is a feed-forward neural network with a standard back-propagation training
      algorithm. The accuracy of the ANN-based method improved significantly, from
      70.4% to 80.5%, when evolutionary information was added to a single sequence as a
      multiple sequence alignment obtained from PSI-BLAST. We have also developed an
      SVM-based method using a primary sequence as input and achieved an accuracy of
      77.4%. The SVM model was modified by adding 36 physicochemical parameters to the
      amino acid sequence information. Finally, ANN- and SVM-based methods were
      combined to utilize the full potential of both techniques. The accuracy and
      Matthews correlation coefficient (MCC) value of SVM, ANN, and combined method are
      78.5%, 80.5%, and 81.8%, and 0.55, 0.63, and 0.64, respectively. These methods
      were trained and tested on a nonredundant data set of 16 proteins, and
      performance was evaluated using "leave one out cross-validation" (LOOCV). Based
      on this study, we have developed a Web server, TBBPred, for predicting
      transmembrane beta-barrel regions in proteins (available at
      http://www.imtech.res.in/raghava/tbbpred).

PMID- 15162483
TI  - Predicted role for the archease protein family based on structural and sequence
      analysis of TM1083 and MTH1598, two proteins structurally characterized through
      structural genomics efforts.
AB  - Recently, the structures of two proteins belonging to the archease family, TM1083
      from Thermotoga maritima and MTH1598 from Methanobacterium thermoautotrophicum,
      have been solved independently by two Protein Structure Initiative structural
      genomics pilot centers using X-ray crystallography and NMR, respectively. The
      archease protein family is a good example of one of the paradoxes of structural
      genomics: Approximately one third of protein structures produced by structural
      genomics centers have no known function and are still annotated as "hypothetical
      proteins" in the Protein Data Bank. In the case of archeases, despite the
      existence of two protein structures and abundant sequence information, there is
      still no function assigned to this protein family. Here, our group predicts,
      based on structural similarity, sequence conservation, and gene context analyses,
      that members of this protein family might function as chaperones or modulators of
      proteins involved in DNA/RNA processing. The conservation of genomic context for
      this protein family is constant from Archaea and Bacteria to humans, and suggests
      that unannotated open reading frames contiguous to them could be novel RNA/DNA
      binding proteins.

PMID- 15162484
TI  - Solution structure of hypothetical Nudix hydrolase DR0079 from extremely
      radiation-resistant Deinococcus radiodurans bacterium.
AB  - Using nuclear magnetic resonance (NMR) based methods, including residual dipolar
      coupling restraints, we have determined the solution structure of the
      hypothetical Deinococcus radiodurans Nudix protein DR0079 (171 residues, MW =
      19.3 kDa). The protein contains eight beta-strands and three alpha-helices
      organized into three subdomains: an N-terminal beta-sheet (1-34), a central Nudix
      core (35-140), and a C-terminal helix-turn-helix (141-171). The Nudix core and
      the C-terminal helix-turn-helix form the fundamental fold common to the Nudix
      family, a large mixed beta-sheet sandwiched between alpha-helices. The residues
      that compose the signature Nudix sequence, GX5EX7REUXEEXGU (where U = I, L, or V
      and X = any amino acid), are contained in a turn-helix-turn motif on the face of
      the mixed beta-sheet. Chemical shift mapping experiments suggest that DR0079
      binds Mg2+. Experiments designed to determine the biological function of the
      protein indicate that it is not a type I isopentenyl-diphosphate delta-isomerase
      and that it does not bind alpha,beta-methyleneadenosine 5'-triphosphate (AMPCPP)
      or guanosine 5'-[beta,gamma-imido]triphosphate (GMPPNP). In this article, the
      structure of DR0079 is compared to other known Nudix protein structures, a
      potential substrate-binding surface is proposed, and its possible biological
      function is discussed.

PMID- 15162485
TI  - Structural and sequence comparisons arising from the solution structure of the
      transcription elongation factor NusG from Thermus thermophilus.
AB  - NusG is an essential bacterial protein modulator of transcriptional elongation
      and termination events, and interacts directly with RNA polymerase and Rho
      protein. Found also in Archaea, NusG shows stretches of sequence similarity to
      the eukaryotic transcription elongation factor Spt5. Herein, the three
      dimensional solution structure of the bacterial NusG from Thermus thermophilus,
      which shows 43% amino acid sequence similarity to the Escherichia coli NusG, is
      described, and a survey of NusG and Spt5 amino acid sequences is presented.
      Although there is a clear evolutionary and functional relationship between these
      proteins, it is evident from the structural, sequence, and biochemical data that
      their binding specificities to both nucleic acids and other proteins differ.

PMID- 15162486
TI  - Probing flexibility and "induced-fit" phenomena in aldose reductase by
      comparative crystal structure analysis and molecular dynamics simulations.
AB  - Aldose reductase is a promising target for the treatment of diabetic
      complications, and as such, has become the focus of various drug design projects.
      As revealed by a survey of available crystal structures, the protein shows
      pronounced induced-fit effects upon ligand binding. Although helping to explain
      the enzyme's substrate promiscuity, phenomena of this kind are still responsible
      for significant complications in structure-based design efforts directed to
      aldose reductase. Accordingly, a deeper understanding of the principles governing
      conformational alterations in this enzyme would be of utmost practical
      importance. As a first step in addressing this issue, molecular dynamics (MD)
      simulations have been carried out. The ultrahigh resolution crystal structure of
      aldose reductase complexed with inhibitor IDD594 served as ideal starting point
      for a set of different simulations of nanosecond time scale: the native complexed
      state with bound inhibitor, the uncomplexed state (after removal of the
      inhibitor) at standard temperature, and the uncomplexed state at elevated
      temperature. The reference simulation of the complex exhibits extraordinary
      stability of the overall fold, whereas two distinct conformational substates are
      found for the binding-site region. In contrast, already at standard temperature
      pronounced changes are observed in the binding region during the simulation of
      the uncomplexed state. Leu300, for example, closes the access to the pocket
      opened by IDD594. On the other hand, conformations around the catalytic site are
      highly conserved, with the His110-Tyr48-NADP+ orientation being stabilized by a
      water molecule. Detailed analysis of the trajectories allows to reveal a set of
      distinct conformational substates that may prove useful as alternative structural
      templates in virtual screening for new aldose reductase inhibitors.

PMID- 15162487
TI  - Toward the active conformations of rhodopsin and the beta2-adrenergic receptor.
AB  - Using sets of experimental distance restraints, which characterize active or
      inactive receptor conformations, and the X-ray crystal structure of the inactive
      form of bovine rhodopsin as a starting point, we have constructed models of both
      the active and inactive forms of rhodopsin and the beta2-adrenergic G-protein
      coupled receptors (GPCRs). The distance restraints were obtained from published
      data for site-directed crosslinking, engineered zinc binding, site-directed spin
      labeling, IR spectroscopy, and cysteine accessibility studies conducted on class
      A GPCRs. Molecular dynamics simulations in the presence of either "active" or
      "inactive" restraints were used to generate two distinguishable receptor models.
      The process for generating the inactive and active models was validated by the
      hit rates, yields, and enrichment factors determined for the selection of
      antagonists in the inactive model and for the selection of agonists in the active
      model from a set of nonadrenergic GPCR drug-like ligands in a virtual screen
      using ligand docking software. The simulation results provide new insights into
      the relationships observed between selected biochemical data, the crystal
      structure of rhodopsin, and the structural rearrangements that occur during
      activation.

PMID- 15162488
TI  - The structure of murine neuroglobin: Novel pathways for ligand migration and
      binding.
AB  - Neuroglobin, a recently discovered globin predominantly expressed in neuronal
      tissue of vertebrates, binds small, gaseous ligands at the sixth coordination
      position of the heme iron. In the absence of an exogenous ligand, the distal
      histidine (His64) binds to the heme iron in the ferrous and ferric states. The
      crystal structure of murine ferric (met) neuroglobin at 1.5 A reveals interesting
      features relevant to the ligand binding mechanism. Only weak selectivity is
      observed for the two possible heme orientations, the occupancy ratio being 70:30.
      Two small internal cavities are present on the heme distal side, which enable the
      His64(E7) side chain to move out of the way upon exogenous ligand binding.
      Moreover, a third, huge cavity (volume approximately 290 A3) connecting both
      sides of the heme, is open towards the exterior and provides a potential
      passageway for ligands. The CD and EF corners exhibit substantial flexibility,
      which may assist ligands in entering the protein and accessing the active site.
      Based on this high-resolution structure, further structure-function studies can
      be planned to elucidate the role of neuroglobin in physiological responses to
      hypoxia.

PMID- 15162489
TI  - A physical reference state unifies the structure-derived potential of mean force
      for protein folding and binding.
AB  - Extracting knowledge-based statistical potential from known structures of
      proteins is proved to be a simple, effective method to obtain an approximate free
      energy function. However, the different compositions of amino acid residues at
      the core, the surface, and the binding interface of proteins prohibited the
      establishment of a unified statistical potential for folding and binding despite
      the fact that the physical basis of the interaction (water-mediated interaction
      between amino acids) is the same. Recently, a physical state of ideal gas, rather
      than a statistically averaged state, has been used as the reference state for
      extracting the net interaction energy between amino acid residues of monomeric
      proteins. Here, we find that this monomer-based potential is more accurate than
      an existing all-atom knowledge-based potential trained with interfacial
      structures of dimers in distinguishing native complex structures from docking
      decoys (100% success rate vs. 52% in 21 dimer/trimer decoy sets). It is also more
      accurate than a recently developed semiphysical empirical free-energy functional
      enhanced by an orientation-dependent hydrogen-bonding potential in distinguishing
      native state from Rosetta docking decoys (94% success rate vs. 74% in 31 antibody
      antigen and other complexes based on Z score). In addition, the monomer potential
      achieved a 93% success rate in distinguishing true dimeric interfaces from
      artificial crystal interfaces. More importantly, without additional parameters,
      the potential provides an accurate prediction of binding free energy of protein
      peptide and protein-protein complexes (a correlation coefficient of 0.87 and a
      root-mean-square deviation of 1.76 kcal/mol with 69 experimental data points).
      This work marks a significant step toward a unified knowledge-based potential
      that quantitatively captures the common physical principle underlying folding and
      binding. A Web server for academic users, established for the prediction of
      binding free energy and the energy evaluation of the protein-protein complexes,
      may be found at http://theory.med.buffalo.edu.

PMID- 15162490
TI  - Partial atomic charges of amino acids in proteins.
AB  - Using a semiempirical quantum mechanical procedure (FCPAC) we have calculated the
      partial atomic charges of amino acids from 494 high-resolution protein
      structures. To analyze the influence of the protein's environment, we considered
      each residue under two conditions: either as the center of a tripeptide with PDB
      structure geometry (free) or as the center of 13-16 amino acid clusters extracted
      from the PDB structure (buried). The partial atomic charges from residues in
      helices and in sheets were separated. The FCPAC partial atomic charges of the
      Cbeta and Calpha of most residues correlate with their helix propensity,
      positively for Cbeta and negatively for Calpha (r2 = 0.76 and 0.6, respectively).
      The main consequence of burying residues in proteins is the polarization of the
      backbone C=O bond, which is more pronounced in helices than in sheets. The
      average shift of the oxygen partial charges that results from burying is -0.120
      in helix and -0.084 in sheet with the charge of the proton as unit. Linear
      correlations are found between the average NMR chemical shifts and the average
      FCPAC partial charges of Calpha (r2 = 0.8-0.85), N (r3 = 0.67-0.72), and Cbeta
      (r2 = 0.62) atoms. Correlations for helix and beta-sheet FCPAC partial charges
      show parallel regressions, suggesting that the charge variations due to burying
      in proteins differentiate between the dihedral angle effects and the polarization
      of backbone atoms.

PMID- 15162491
TI  - Folding thermodynamics of three beta-sheet peptides: a model study.
AB  - We study the folding thermodynamics of a beta-hairpin and two three-stranded beta
      sheet peptides using a simplified sequence-based all-atom model, in which folding
      is driven mainly by backbone hydrogen bonding and effective hydrophobic
      attraction. The native populations obtained for these three sequences are in good
      agreement with experimental data. We also show that the apparent native
      population depends on which observable is studied; the hydrophobicity energy and
      the number of native hydrogen bonds give different results. The magnitude of this
      dependence matches well with the results obtained in two different experiments on
      the beta-hairpin.

PMID- 15162492
TI  - Strategy for supplementing structure calculations using limited data with
      hydrophobic distance restraints.
AB  - Introductory biochemistry texts often note that the fold of a protein is
      completely defined when the dihedral angles phi and psi are known for each amino
      acid. This assertion was examined with torsion angle dynamics and simulated
      annealing (TAD/SA) calculations of protein G using only dihedral angle
      restraints. When all dihedral angles were restrained to within 1 degrees of the
      values of the X-ray structure, the TAD/SA structures gave a backbone root mean
      square deviation to the target of 4 A. Factors that contributed to divergence
      from the correct solution include deviations of peptide bonds from planarity,
      internal conflicts resulting from the nonuniform energies of different phi, psi
      combinations, and relaxation to extended conformations in the absence of long
      range constraints. Simulations including hydrogen-bond restraints showed that
      even a few long-range contacts constrain the fold better than a complete set of
      accurate dihedral restraints. A procedure is described for TAD/SA calculations
      using hydrogen-bond restraints, idealized dihedral restraints for residues in
      regular secondary structures, and "hydrophobic distance restraints" derived from
      the positions of hydrophobic residues in the amino acid sequence. The hydrogen
      bond restraints are treated as inviolable, whereas violated hydrophobic
      restraints are removed following reduction of restraint upper bounds from 2 to 1
      times the predicted radius of gyration. The strategy was tested with simulated
      restraints from X-ray structures of proteins from different fold classes and NMR
      data for cold shock protein A that included only backbone chemical shifts and
      hydrogen bonds obtained from a long-range HNCO experiment.

PMID- 15162493
TI  - Hydrophobic complementarity in protein-protein docking.
AB  - Formation of hydrophobic contacts across a newly formed interface is
      energetically favorable. Based on this observation we developed a geometric
      hydrophobic docking algorithm that estimates quantitatively the hydrophobic
      complementarity at protein-protein interfaces. Each molecule to be docked is
      represented as a grid of complex numbers, storing information regarding the shape
      of the molecule in the real part and information regarding the hydropathy of the
      surface in the imaginary part. The grid representations are correlated using fast
      Fourier transformations. The algorithm is used to compare the extent of
      hydrophobic complementarity in oligomers (represented by D2 tetramers) and in
      hetero-dimers of soluble proteins (complexes). We also test the implication of
      hydrophobic complementarity in distinguishing correct from false docking
      solutions. We find that hydrophobic complementarity at the interface exists in
      oligomers and in complexes, and in both groups the extent of such complementarity
      depends on the size of the interface. Thus, the non-polar portions of large
      interfaces are more often juxtaposed than non-polar portions of small interfaces.
      Next we find that hydrophobic complementarity helps to point out correct docking
      solutions. In oligomers it significantly improves the ranks of nearly correct
      reassembled and modeled tetramers. Combining geometric, electrostatic and
      hydrophobic complementarity for complexes gives excellent results, ranking a
      nearly correct solution < 10 for 5 of 23 tested systems, < 100 for 8 systems and
      < 1000 for 19 systems.

PMID- 15162495
TI  - Probabilistic description of protein alignments for sequences and structures.
AB  - A number of equally optimal alignments inherently exist in the sequence and
      structure comparisons among proteins. To represent the sub-optimal alignments
      systematically, we have developed a method of generating probabilistic alignments
      for sequences and structures, by which the correspondence between pairs of
      residues is evaluated in a probabilistic manner. Our method uses the periodic
      boundary condition to avoid the entropy artifact favoring full-length matches. In
      the structure comparison, the environmental effects are incorporated by the mean
      field approximation. We applied this method in comparisons of two pairs of
      proteins with internal symmetry; the first set were proteins of TIM-barrel fold
      and the second were beta-trefoil fold. These pairs are expected to have distinct
      sub-optimal alignments suitable for probabilistic description with the periodic
      boundary. It was shown that the sequence and structure alignments are consistent
      with each other and that the alignments with the highest probability represent
      circular permutation.

PMID- 15162494
TI  - A method for simultaneous alignment of multiple protein structures.
AB  - Here, we present MultiProt, a fully automated highly efficient technique to
      detect multiple structural alignments of protein structures. MultiProt finds the
      common geometrical cores between input molecules. To date, most methods for
      multiple alignment start from the pairwise alignment solutions. This may lead to
      a small overall alignment. In contrast, our method derives multiple alignments
      from simultaneous superpositions of input molecules. Further, our method does not
      require that all input molecules participate in the alignment. Actually, it
      efficiently detects high scoring partial multiple alignments for all possible
      number of molecules in the input. To demonstrate the power of MultiProt, we
      provide a number of case studies. First, we demonstrate known multiple alignments
      of protein structures to illustrate the performance of MultiProt. Next, we
      present various biological applications. These include: (1) a partial alignment
      of hinge-bent domains; (2) identification of functional groups of G-proteins; (3)
      analysis of binding sites; and (4) protein-protein interface alignment. Some
      applications preserve the sequence order of the residues in the alignment,
      whereas others are order-independent. It is their residue sequence order
      independence that allows application of MultiProt to derive multiple alignments
      of binding sites and of protein-protein interfaces, making MultiProt an extremely
      useful structural tool.

PMID- 15162496
TI  - Crystal structure of a glycerophosphodiester phosphodiesterase (GDPD) from
      Thermotoga maritima (TM1621) at 1.60 A resolution.

PMID- 15162498
TI  - Crystal structure of the TM1442 protein from Thermotoga maritima, a homolog of
      the Bacillus subtilis general stress response anti-anti-sigma factor RsbV.

PMID- 15162497
TI  - Crystal structure of a ribose-5-phosphate isomerase RpiB (TM1080) from Thermotoga
      maritima at 1.90 A resolution.

PMID- 15162499
TI  - Differential regulation of chondrogenic differentiation by the serotonin2B
      receptor and retinoic acid in the embryonic mouse hindlimb.
AB  - Retinoic acid (RA) synthesizing and metabolizing enzymes are coordinately
      expressed with serotonin 2B (5-HT2B) receptors at sites of epithelial-mesenchymal
      (E-M) interaction in the mouse embryo (Bhasin et al., 1999). The promoter of the
      5-HT2B receptor contains potential RA response element (RAREs) as well as an AP-2
      site. Because both retinoid and serotonergic signaling have been implicated in
      the regulation of chondrogenic differentiation, the present study investigated
      whether these signals may work together to regulate this morphogenetic process in
      hindlimb bud micromass cultures. Results indicate that 5-HT promotes [35S]sulfate
      incorporation (chondrogenic differentiation) by activation of 5-HT2B receptors,
      which use the mitogen activated protein kinase (p42 MAPK) signal transduction
      pathway, whereas RA dose-dependently inhibits sulfate incorporation and promotes
      expression of RARbeta, which could lead to inhibition of p38 MAPK. No evidence
      was found to support the possibility that RA negatively regulates expression of 5
      HT2B receptors. Taken together, these results suggest that 5-HT and RA may act as
      opposing signals to regulate chondrogenic differentiation in the developing
      hindlimb, possibly mediated by different MAPK signal transduction pathways.

PMID- 15162501
TI  - Twist is required for patterning the cranial nerves and maintaining the viability
      of mesodermal cells.
AB  - Twist encodes a basic helix-loop-helix transcription factor that is required for
      normal craniofacial morphogenesis in the mouse. Loss of Twist activity in the
      cranial mesenchyme leads to aberrant migratory behaviour of the neural crest
      cells, whereas Twist-deficient neural crest cells are located in an inappropriate
      location in the first branchial arch and display defective osteogenic and
      odontogenic differentiation (Soo et al. [2002] Dev. Biol. 247:251-270). Results
      of the present study further show that loss of Twist impacts on the patterning of
      the cranial ganglia and nerves but not that of the peripheral ganglia and nerves
      in the trunk region of the body axis. Analyses of the expression of molecular
      markers of early differentiation of the paraxial mesoderm and the histogenetic
      potency of somites of Twist(-/-) embryos reveal that Twist-deficient somites can
      differentiate into muscles, cartilage, and bones, albeit less prolifically. Twist
      function, therefore, is not essential for mesoderm differentiation. The poor
      growth of the Twist-deficient somites after transplantation to the ectopic site
      may be attributed to reduced proliferative capacity and extensive apoptosis of
      the paraxial mesoderm, suggesting that Twist is required for maintaining cell
      proliferation and viability in the mesodermal progenitors.

PMID- 15162500
TI  - Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis.
AB  - Wnt4(-/-) XX gonads display features normally associated with testis
      differentiation, suggesting that WNT4 actively represses elements of the male
      pathway during ovarian development. Here, we show that follistatin (Fst), which
      encodes a TGFbeta superfamily binding protein, is a downstream component of Wnt4
      signaling. Fst inhibits formation of the XY-specific coelomic vessel in XX
      gonads. In addition, germ cells in the ovarian cortex are almost completely lost
      in both Wnt4 and Fst null gonads before birth. Thus, we propose that WNT4 acts
      through FST to regulate vascular boundaries and maintain germ cell survival in
      the ovary.

PMID- 15162502
TI  - Short upstream region drives dynamic expression of hypoxia-inducible factor
      1alpha during Xenopus development.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a central role in regulating
      oxygen-dependent gene expression and is involved in a range of pathways
      implicated in cellular survival, proliferation, and development. While the
      posttranslational regulation of HIF-1alpha is well characterized, the relative
      importance of its control at the transcriptional level during development remains
      less clear. Although the mouse and human promoter regions have been analyzed in
      vitro, to date, there has been no in vivo analysis of any vertebrate HIF-1alpha
      promoter. To investigate the transcriptional regulation of HIF-1alpha during
      development of the amphibian Xenopus laevis, we have described the gene's
      expression pattern and isolated the xHIF-1alpha upstream regulatory regions. We
      show xHIF-1alpha mRNA to be constitutively expressed at low levels throughout
      embryogenesis, but with significant up-regulation during gastrula stages, and
      subsequently, in specific regions of the central nervous system and axial
      tissues. Our functional analysis using a series of truncated xHIF-1alpha promoter
      constructs demonstrates that a 173-bp region of the proximal promoter, which is
      100% conserved among five allelic variants, is sufficient to drive correct
      expression in transgenic embryos. Although these results are corroborated by a
      parallel set of in vitro transfection experiments in a Xenopus cell line, some
      key differences suggest the importance of using transgenic methods in conjunction
      with in vitro assays.

PMID- 15162503
TI  - Development of heart valve leaflets and supporting apparatus in chicken and mouse
      embryos.
AB  - Abnormalities in valvuloseptal development significantly contribute to congenital
      heart defects, yet the underlying causes are complex and poorly understood. Early
      cardiac regulatory genes are differentially expressed during valvuloseptal
      development, consistent with novel functions during heart chamber formation in
      chicken and mouse embryos. Distinct valve cell lineages were identified in the
      leaflets, chordae tendineae, and myotendinous junctions with the papillary
      muscles based on restricted expression of extracellular matrix molecules.
      Specific cell types within these structures demonstrate characteristics of
      chondrogenesis and tendon development, identified by scleraxis, type II collagen,
      and tenascin expression. In chicken embryos, valve remodeling and maturation
      accompanies a decrease in mitotic index indicated by reduced bromodeoxyuridine
      incorporation. Analysis of Tie2-cre x ROSA26R mice demonstrates that mature valve
      structures, including the atrioventricular and outflow tract semilunar valve
      leaflets, chordae tendineae, and the fibrous continuity that connects the septal
      leaflets of mitral and tricuspid valves, arise from endothelial cells of the
      endocardial cushions. Together, these studies provide novel insights into the
      origins and cell lineage diversity of mature valve structures in the developing
      vertebrate heart.

PMID- 15162504
TI  - Time course of programmed cell death in Ciona intestinalis in relation to mitotic
      activity and MAPK signaling.
AB  - Programmed cell death (PCD) in the ascidian species Ciona intestinalis (Tunicata;
      Chordata) is investigated from early larvae to juvenile stages, by means of
      digoxigenin-based terminal deoxynucleotidyl transferase-mediated biotinylated UTP
      nick end labeling (TUNEL) technique. At first, PCD in the swimming larva affects
      trunk mesenchyme and central nervous system (CNS), then it participates
      extensively to metamorphosis, until it is restricted to developing organs of
      juveniles. Analysis of patterns of cell death and division in the larval CNS
      question old models on the genesis of the adult C. intestinalis brain. Upon
      performing immunochemical and functional assays for mitogen-activated protein
      kinase (MAPK) kinase kinase-1 (MEKK1), MAPK kinase 1/2 (MEK1/2), c-Jun NH2
      terminal kinase (JNK), and dual phosphorylated extracellular regulated kinase 1/2
      (dpERK1/2), the neurogenic competence of the larval brain appears to rely on a
      combinatorial regulation of PCD by the mitogen-activated protein kinase signaling
      cascade. These results show that, in tunicates, PCD consists of a multistep
      program implicated in growth and patterning with various roles.

PMID- 15162505
TI  - E-cadherin regulates cell movements and tissue formation in early zebrafish
      embryos.
AB  - E-cadherin is maternally expressed in most vertebrate species, but its function
      during early development of the vertebrate embryo proper is unknown. To directly
      examine E-cadherin gene (cdh1) function in zebrafish, morpholino oligonucleotides
      (MOs) that inhibit E-cadherin protein (Cdh1) expression were injected into
      embryos. Cdh1 knockdown reduced embryo survival. In early cdh1 MO-injected
      embryos, the cleavage plane orientation between blastomeres was irregular and
      adhesion defects prevented normal compaction. Cdh1 knockdown inhibited epiboly
      cell movements. Epiboly delay caused yolk cell lysis and produced embryos with a
      bifurcated embryonic axis. Cdh1 knockdown inhibited gastrulation cell movements,
      causing defects in convergence and extension. Additionally, prechordal plate
      derivatives were absent in Cdh1 knockdown embryos even though presumptive
      prechordal plate markers were induced normally. E-cadherin mRNA coinjection
      demonstrated the specificity of cdh1 MO-induced defects. Our experiments
      illustrate the importance of cdh1 in regulating morphogenetic cell movements and
      tissue formation in the early embryo.

PMID- 15162506
TI  - Arrested pulmonary alveolar cytodifferentiation and defective surfactant
      synthesis in mice missing the gene for parathyroid hormone-related protein.
AB  - Parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor expression are
      developmentally regulated in lung epithelium and adepithelial mesenchyme,
      respectively. To test the hypothesis that PTHrP is a developmental regulator of
      terminal airway development, we investigated in vivo and in vitro models of
      alveolar cytodifferentiation using mice in which the gene encoding PTHrP was
      ablated by homologous recombination. We have determined that fetal and newborn
      PTHrP(-/-) lungs showed delayed mesenchymal-epithelial interactions, arrested
      type II cell differentiation, and reduced surfactant lamellar body formation and
      pulmonary surfactant production. Embryonic PTHrP(-/-) lung buds cultured in the
      absence of skeletal constriction or systemic compensating factors also exhibited
      delayed alveolar epithelial (type II cell) and mesenchymal cytodifferentiation,
      as well as a > 40% inhibition of surfactant phospholipid production (n = 3-5).
      Addition of exogenous PTHrP to embryonic PTHrP(-/-) lung cultures normalized
      interstitial cell morphology and surfactant phospholipid production. The
      importance of PTHrP as an endogenous regulatory molecule in mammalian lung
      development is supported by the findings that ablation of PTHrP expression in
      isolated developing lung is sufficient to disrupt normal development of the
      alveolar ducts and the centriacinar regions.

PMID- 15162507
TI  - Construction and analysis of a subtracted library and microarray of cDNAs
      expressed specifically in chicken heart progenitor cells.
AB  - A subtracted library was constructed of genes expressed specifically in the chick
      precardiac mesoendoderm. The subtracted library was obtained by hybridization of
      nucleic acids derived from a starting tester library of stage 4-7 chick
      precardiac mesoendoderm and a starting driver library of stage 2 area pellucida.
      Approximately 11,000 clones from the resulting subtracted library were printed
      onto a microarray. Screening of the microarray with probes derived from cardiac
      and noncardiac tissues, followed by in situ hybridization during chick embryo
      development, has identified multiple cardiac-specific genes, including several
      that have not been characterized previously. The microarray will be useful for
      future attempts to identify additional novel cardiac-specific genes, as well as
      to characterize patterns of gene expression during heart differentiation.

PMID- 15162508
TI  - Functional knockdown of neuropilin-1 in the developing chick nervous system by
      siRNA hairpins phenocopies genetic ablation in the mouse.
AB  - The chick embryo is widely used for the study of vertebrate development, but a
      general, reliable loss-of-function strategy for the analysis of gene function is
      currently not available. By using small inhibitory hairpin RNA (siRNA) molecules
      generated by the mouse U6 promoter, we have applied an RNA interference approach
      to achieve quantitative knockdown of the neuropilin-1 (Nrp-1) receptor in chick
      embryos. Functional knockdown was evident in the abolition of Sema3A-induced
      growth cone collapse in Nrp-1-siRNA but not Nrp-2-siRNA-expressing dorsal root
      ganglion (DRG) neurons. Two nervous system defects in Nrp-1 mutant mice were
      phenocopied in embryos treated with Nrp-1 siRNA. First, DRG axons prematurely
      entered the dorsal horn and projected inappropriately. Second, targeted early
      migrating neural crest cells destined for the sympathetic chain arrested
      ectopically within ventral spinal nerve roots. Localized knockdown induced by
      specific siRNA constructs will allow rapid functional analysis of genes
      regulating chick neural development whilst circumventing embryonic lethal effects
      often associated with global gene knockout in the mouse.

PMID- 15162509
TI  - Rapid triple-labeling method combining in situ hybridization and double
      immunocytochemistry.
AB  - A new, rapid method is described for combining in situ hybridization and
      immunocytochemistry to define cell populations and to map three-dimensional
      movements of groups of labeled cells within developing chick embryos. The method
      allows fluorescently labeled cells to be followed in living embryos and
      subsequently detected as a permanent reaction product for detailed three
      dimensional analysis by immunocytochemistry in histological serial sections. Cell
      identity can be ascertained using a specific riboprobe and in situ hybridization.
      With this approach, the movements of two groups of cells can be mapped
      simultaneously (using two different fluorescent trackers and, subsequently, two
      different chromogens for immunocytochemistry) to analyze relative movements
      within an embryo, and when combined with in situ hybridization with a specific
      riboprobe for cell identity, allows fate mapping studies to be conducted using
      molecular criteria, rather than solely at morphological/positional criteria. The
      improved method enables the investigator to extract substantially more
      information from individual embryos, maximizing the results obtained from labor
      intensive fate mapping studies.

PMID- 15162510
TI  - Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial
      cells.
AB  - We report the cloning and characterization of a novel epidermal growth factor
      (EGF) domain gene that was identified in a retroviral gene entrapment screen and
      is expressed in endothelial cells. This gene encodes a protein of 278 amino acids
      with an amino-terminal signal peptide and two centrally located EGF-like domains.
      We have named this novel gene in accordance with the guidelines of the Mouse
      Genome Informatics group Egfl7, for EGF-like domain 7. Egfl7 mRNA is expressed in
      highly vascularized adult tissues such as the lung, heart, uterus, and ovary. In
      addition, Egfl7 is expressed early during mouse embryogenesis and in
      undifferentiated murine embryonic stem cells. The analysis of Egfl7 expression in
      embryonic day 9.5 embryos by in situ hybridization indicates that Egfl7 is
      expressed in vascular structures in both the embryo proper and the yolk sac and
      at sites of mesodermal precursors of angioblasts. Within the cell, EGFL7 protein
      is localized to the endoplasmic reticulum and Golgi apparatus, suggesting that
      the protein is targeted for secretion. Indeed, recombinant EGFL7 is readily
      detectable in the supernatant media of transiently transfected HEK293 cells. We
      also report the identification of an Egfl7 paralog, Egfl8, and show that EGFL8
      protein shares similar domains and molecular weight with EGFL7.

PMID- 15162511
TI  - Comparative expression analysis of the MAGED genes during embryogenesis and brain
      development.
AB  - The MAGED gene subfamily contains three genes in mouse and four in human. The
      MAGED1, D2, and D3 proteins are highly conserved between mouse and human, whereas
      paralogues are less conserved between each other. This finding suggests that each
      MAGED protein exerts a distinct function. To get a better insight into their
      physiological roles, we have analyzed their expression patterns during
      embryogenesis and brain development. In the mouse, Maged3 expression is
      restricted to the central nervous system where it was mostly detected in
      postmitotic neurons. Maged2 is mainly expressed in tissues of mesodermal origin.
      The expression pattern of Maged1 roughly summarizes that of Maged2 and Maged3;
      however, contrary to that of Maged3, it includes the proliferative zones of the
      nervous system. We observed a discrepancy between Maged1 expression levels of RNA
      and protein, suggesting that its expression is regulated at a posttranscriptional
      level during the mouse development.

PMID- 15162512
TI  - Upper beak truncation in chicken embryos with the cleft primary palate mutation
      is due to an epithelial defect in the frontonasal mass.
AB  - In this study, we used the chicken mutant strain known as cleft primary palate
      (cpp) to study the mechanisms of beak outgrowth. cpp mutants have complete
      truncation of the upper beak with normal development of the lower beak. Based on
      structural analysis and grafts of facial prominences, we localized the defect to
      the frontonasal mass and its derivatives. Several explanations that would account
      for the outgrowth defect were investigated, including abnormal expression of
      genes in the frontonasal epithelium, intrinsic defects in epithelium and/or
      mesenchyme defects in epithelial-mesenchymal signalling, a localized decrease in
      cell proliferation or a localized increase in programmed cell death. One of the
      genes expressed in the frontonasal epithelial growth zone, Fgf8, failed to down
      regulate and was maintained for at least 48 hr beyond the time when down
      regulation normally occurs. Recombination experiments further illustrated that
      the frontonasal mass epithelium was abnormal in the cpp mutants, whereas mutant
      mesenchyme was capable of normal outgrowth when combined with wild-type
      epithelium. Cell proliferation was not decreased in mutant embryos nor was cell
      death initially increased. Later, at stages 31-32, when the prenasal cartilage
      begins directed outgrowth, there was an increase in cell death within the mutant
      upper but not lower beak cartilage. The cpp beak truncation, therefore, is due to
      an epithelial defect in the frontonasal mass that is coincident with a failure to
      down-regulate expression of Fgf8.

PMID- 15162513
TI  - Slit and robo expression in the developing mouse lung.
AB  - Mammalian lung development is mediated through complex interactions between
      foregut endoderm and surrounding mesenchyme. As airway branching progresses, the
      mesenchyme undergoes dramatic remodeling and differentiation. Little is
      understood about the mechanisms that direct mesenchymal organization during lung
      development. A screen for candidate genes mediating this process identified Slit,
      a ligand for the Roundabout (Robo) receptor previously associated with guidance
      of axonal projections during central nervous system development. Here, we
      demonstrate by in situ hybridization that two Slit genes (Slit-2 and Slit-3) and
      two Robo genes (Robo-1 and Robo-2) are expressed in fetal lung mesenchyme. Slit-2
      and Robo-1 expression is present throughout mesenchyme at midgestation and is not
      detectable by newborn day 1. Slit-3 and Robo-2 expression is restricted to
      specific, complementary subsets of mesenchyme. Robo-2 is expressed in mesenchymal
      cells immediately adjacent to large airways, whereas Slit-3 expression
      predominates in mesenchyme remote from airway epithelium. The temporal and
      spatial distribution of Slit and Robo mRNAs indicate that these genes may direct
      the functional organization and differentiation of fetal lung mesenchyme.

PMID- 15162514
TI  - Expression analysis of the Drosophila pipsqueak family members fernandez/distal
      antenna and hernandez/distal antenna related.
AB  - The "pipsqueak" family is composed of proteins that contain a pipsqueak motif, a
      previously characterised DNA binding domain, and thus represents a new family of
      potential transcription factors. Previous functional characterisation of several
      Drosophila genes encoding pipsqueak domain-containing proteins has shown their
      crucial role in development. Here, I report the embryonic, larval, and pupal
      expression pattern of two Drosophila genes, fernandez/distal antenna and
      hernandez/distal antenna related, which encode protein members of the pipsqueak
      family with similar pipsqueak motifs. Furthermore, I show that, consistently with
      their expression pattern, these two genes are required in the nervous system
      during the embryonic development.

PMID- 15162515
TI  - HMG box transcription factor gene Hbp1 is expressed in germ cells of the
      developing mouse testis.
AB  - HMG box containing protein 1 (HBP1) is a high mobility group domain
      transcriptional repressor that regulates proliferation in differentiated tissues.
      We have found mouse Hbp1 to be expressed strongly in the embryonic mouse testis
      from approximately 12.5 days post coitum, compared with low levels of expression
      in the embryonic ovary. Expression of Hbp1 is maintained in the developing testis
      beyond the onset of spermatogenesis after birth. Whole-mount in situ
      hybridisation analysis showed that expression of Hbp1 in the XY gonad is
      localized within the developing testis cords, the precursors of the seminiferous
      tubules. Expression of Hbp1 is not apparent in testis cords of gonads from
      homozygous W(e) mutant embryos, which lack germ cells. In situ hybridisation
      analysis on cryosectioned embryonic testis indicated that Hbp1 expression
      resembles that of the germ cell marker Oct4. We conclude that Hbp1 is up
      regulated specifically in germ cells of the developing XY gonad. The expression
      of Hbp1 in XY germ cells appears to correlate with the onset of mitotic arrest in
      these cells.

PMID- 15162516
TI  - Cloning and expression analysis of the mouse stroma marker Snep encoding a novel
      nidogen domain protein.
AB  - The vertebrate kidney develops through a series of mesenchymal-epithelial
      interactions between the ureteric bud and the metanephrogenic mesenchyme to form
      nephrons and the collecting system, which are both embedded in the renal
      interstitium. The interstitial stromal cells are an essential prerequisite for
      regular kidney development, but their origin and function is poorly understood.
      They are found in the kidney periphery and the medulla and are likely derived
      from the kidney mesenchyme and/or from migrating neural crest cells. During late
      kidney development, stromal cells are lost through massive apoptosis. We have
      identified a novel marker of kidney stroma cells, Snep (stromal nidogen
      extracellular matrix protein), that is additionally expressed in mesenchymal
      cells of other embryonic tissues and within the nervous system. Of interest, Snep
      transcripts are also found at sites of embryonic apoptosis. Furthermore,
      comparative expression analysis of kidney stroma markers suggests that Snep is
      expressed in a specific subpopulation of stromal cells and may provide
      environmental cues to support regular development.

PMID- 15162517
TI  - Abnormal lymphatic development in trisomy 16 mouse embryos precedes nuchal edema.
AB  - Ultrasound measurement of increased nuchal translucency is a method of risk
      assessment for heart malformations and trisomy 21 in human pregnancy. The
      developmental background of this nuchal edema is still not sufficiently
      understood. We have studied the process in trisomy 16 mice that show nuchal edema
      and heart malformations. We used trisomy 16 and wild-type (WT) embryos from
      embryonic day (E) 12.5 to E18.5. In WT embryos at E13, bilateral jugular
      lymphatic sacs are visible that share a lymphatic-venous membrane with the
      jugular vein. We could not in any case discern a valve between these vessels. At
      E14 in the TS16 embryos, the lymphatic sacs become enlarged showing abnormally
      thickened endothelium, specifically at the site of the membrane. In these
      embryos, severe edema develops in the nuchal region. There is a very close
      colocalisation of the nerves with the vascular structures. The start of
      reorganization of the jugular lymphatic sac to a lymph node is observed in both
      wild-type and TS16 but is diminished in the latter. In conclusion, abnormal size
      and structure of the jugular lymphatic sacs coincides with the development of
      nuchal edema. A disturbance of lymphangiogenesis might be the basis for increased
      nuchal translucency that is often observed in diseased human fetuses.

PMID- 15162518
TI  - A Nice development: The first joint meeting of the British and French Societies
      for Developmental Biology, 13-16th September, 2003, Nice, France.
AB  - Held this autumn on the beautiful Cote d'Azur, the first joint meeting of the
      BSDB and SFBD provided delegates with the perfect informal setting for discussion
      spanning a broad cross-section of Developmental Biology. Participants' interests
      were diverse, ranging from the implementation of genome-wide approaches aimed at
      identifying all the molecular components of cell proliferation, signalling,
      patterning, and morphogenesis, to those engaged in capturing mesmerising glimpses
      of the minute and intricate workings of the cell. The meeting considered a wide
      spectrum of model organisms, including the simple plant Arabidopsis, the
      invertebrates Dictyostelium, Caenorhabditis elegans, and Drosophila melanogaster,
      the ascidian Ciona intestinalis, and the vertebrates Xenopus, zebrafish, chick,
      and mouse. Such a diverse approach served to highlight both similarities and
      differences in the molecular mechanisms that govern embryonic development among
      different species. Here, we highlight a few aspects of the meeting that
      illustrate this point.

PMID- 15162520
TI  - Blossoming of gastroenterology during the twentieth century.

PMID- 15162521
TI  - Survival of patients with stomach cancer in Changle city of China.
AB  - AIM: The survival rate of patients with stomach cancer is used to evaluate the
      effects of treatments. The short- and mid-term survival of patients on the
      present level of treatments can be described by calculating 1- to 5-year survival
      rates. The aims of this study were to document patterns of survival after
      treatments for stomach cancer in Changle city and analyze whether the stage of
      cancer and the way of treatment impacted on survival of patients or not. METHODS:
      A total number of 745 patients with stomach cancer reported in the Changle Cancer
      Registry from 1993 to 1998 were investigated with respect to the disease
      condition, the way of treatment and survival time. 1- to 5-year survival rates
      were estimated by using life-table method. RESULTS: The 1- to 5-year survival
      rates in the patients with stomach cancer in Changle city were 54.23%, 41.77%,
      37.95%, 33.98% and 30.47%, respectively. The 1- to 5-year survival rates in stage
      I or II group were 3, 6.1, 7.4, 8.9 and 9.8 times as high as those in stage III
      or IV group, respectively. The 1- to 5-year survival rates in operation group
      were 3.5, 8.7, 11.2, 11.7 and 19 times as high as those in no operation group,
      respectively. For the patients with stage III or IV stomach cancer the 1-year
      survival rate in operation group was 3 times as high as that in no operation
      group and 2-year survival rate in operation group was 11.9 times as high as that
      in no operation group. For the patients with stage III or IV stomach cancer, the
      differences of the survival rates average survival times between total
      gastrectomy and partial gastrectomy were not significant and the median survival
      times in these 2 groups were 8 mo and 9 mo, respectively. CONCLUSION: Mid-term
      survival rates of patients with stomach cancer in Changle city are low. Stage of
      cancer is an important factor influencing survival of patients with stomach
      cancer. Surgery is an effective treatment for the patients with stage IV cancer
      and can raise short- and mid-term survival rates. Total gastrectomy should not be
      encouraged for the patients with late stage of cancer.

PMID- 15162522
TI  - Gender difference in clinicopathologic features and survival of patients with
      hepatocellular carcinoma.
AB  - AIM: To determine the influence of gender on the clinicopathologic
      characteristics and survival of patients with hepatocellular carcinoma (HCC).
      METHODS: A retrospective analysis of medical records was performed in 299
      patients with HCC and their clinicopathologic features and survival were compared
      in relation to gender. RESULTS: There were 260 male (87%) and 39 female patients
      (13%), with a male-to-female ratio of 6.7:1. Female patients had lower mean serum
      bilirubin levels (P=0.03), lower proportion of alcohol abuse (P=0.002), smaller
      mean tumor size (P=0.02), more frequent nodular type but less frequent massive
      and diffuse types of HCC (P=0.01), were less advanced in Okuda's staging
      (P=0.04), and less frequently associated with venous invasion (P=0.03). The
      median survivals in females (14 mo) were significantly longer than that of male
      patients (4 mo) (P=0.004, log-rank test). Multivariate analysis demonstrated that
      high serum alpha-fetoprotein levels, venous invasion, extrahepatic metastasis and
      lack of therapy were independent factors related to unfavorable prognosis.
      However, gender did not constitute a predictive variable associated with patient
      survival. CONCLUSION: Female patients tend to have higher survival rates than
      males. These differences were probably due to more favorable pathologic features
      of HCC at initial diagnosis and greater likelihood to undergo curative therapy in
      female patients.

PMID- 15162523
TI  - Effect of phosphorus-32 glass microspheres on human hepatocellular carcinoma in
      nude mice.
AB  - AIM: To study the effects of phosphorus-32 glass microspheres ((32)P-GMS) on
      human hepatocellular carcinoma in nude mice. METHODS: Human liver cancer cell
      line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice.
      Then the 40 tumor-bearing BALB/ c nude mice were allocated into treatment group
      (n=32) and control group (n=8). In the former group different doses of (32)P-GMS
      were injected into the tumor mass, while in the latter nonradioactive (31)P-GMS
      was injected into the tumor mass. The experimental animals were sacrificed on the
      14th day. The ultrastructural changes of tumor in both treatment group and
      control group were studied with transmission electron microscopy (TEM) and
      stereology. RESULTS: In treatment group, a lot of tumor cells were killed and the
      death rate of tumor cells was much higher (35-70%). Ultrastructurally, severe
      nuclear damage was observed in the death cells. The characteristics of apoptosis
      such as margination of heterochromatin was also found in some tumor cells.
      Besides, well differentiated tumor cells, degenerative tumor cells and some
      lymphocytes were seen. The skin and muscle adjacent to the tumor were normal. In
      control group, the tumor consisted of poorly differentiated tumor cells, in which
      there were only a few of dead cells(5%). Stereological analysis of
      ultrastructural morphology showed that Vv of nuclei (53.31+/-3.46) and Vv of
      nucleoli(20.40+/-1.84) in the control group were larger than those(30.21+/-3.52
      and 10.96+/-2.52) in the treatment group respectively (P<0.01), and Vv of RER
      (3.21+/-0.54) and Vv of mitochondria (4.53+/-0.89) in the control group were
      smaller than those (8.67+/-1.25 and 7.12+/-0.95) in the treatment group
      respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi
      (27.12 um(2)/100 um(3)+/-11.84 um(2)/100 um(3)) in the control group was smaller
      than that (78.81 um(2)/100 um(3)+/- 19.69 um(2)/100 um(3)) in the treatment group
      (P<0.01). But Vv of lipid particles (3.71+/-1.97) and Vv of vacuoles (5.72+/
      1.58) were much larger than those (0.30+/-0.16 and 0.35+/-0.15) in the treatment
      group respectively (P<0.05, P<0.01). CONCLUSION: The experimental results
      indicate that local administration of (32)P-GMS can produce obvious effect on
      liver cancer cells and the anticancer effect of (32)P-GMS is directly
      proportional to the dose administrated. Ultrastructural stereology can also show
      the effect of (32)P-GMS on the normalization of tumor cells, which is beneficial
      to the prognosis and treatment of patients. Moreover, local administration of
      (32)P-GMS is also safe.

PMID- 15162524
TI  - Structure analysis and expressions of a novel tetratransmembrane protein,
      lysosoma-associated protein transmembrane 4 beta associated with hepatocellular
      carcinoma.
AB  - AIM: To analyze the structure and expressions of the protein encoded by an HCC
      associated novel gene, lysosome-associated protein transmembrane 4 beta
      (LAPTM4B). METHODS: Primary structure and fundamental characteristics of LAPTM4B
      protein were analysed with bioinformatics. Expressions of LAPTM4B in HCC tissues
      and various cell lines were detected using polyclonal antibodies and Western
      blot. RESULTS: LAPTM4B encoded two isoforms of proteins with molecular masses 35
      ku and 24-ku, respectively. The expression level of LAPTM4B-35 protein in HCC
      tissues was dramatically upregulated and related to the differentiation status of
      HCC tissues, and it was also high in some cancer cell lines. Computer analysis
      showed LAPTM4B was an integral membrane protein with four transmembrane domains.
      LAPTM4B showed relatively high homology to LAPTM4A and LAPTM5 in various species.
      CONCLUSION: LAPTM4B gene encoded two isoforms of tetratransmembrane proteins,
      LAPTM4B-35 and LAPTM4B-24. The expression of LAPTM4B-35 protein is upregulated
      and associated with poor differentiation in human HCC tissues, and also at high
      levels in some cancer cell lines. LAPTM4B is an original and conserved protein.

PMID- 15162525
TI  - Quantitative detection of common deletion of mitochondrial DNA in hepatocellular
      carcinoma and hepatocellular nodular hyperplasia.
AB  - AIM: To study the deletion of mitochondiral DNA in hepatocellular carcinoma and
      hepatocellular nodular hyperplasia and its significance in the development of
      cancer. METHODS: Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were
      quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas
      (HCC) and corresponding noncancerous liver tissues and 27 hepatocellular nodular
      hyperplasiae (HNH). RESULTS: A novel CD (4 981 bp) was detected in 85% (23/27)
      and 83%(22/27) of HCC and HNH tumor tissues, respectively, which were
      significantly higher than that in paired noncancerous liver tissues (57%, 15/27)
      (P<0.05). The CD/WT-mtDNA ratio in HCC tumors was 0.00092 (median, interquartile
      range, 0.0001202-0.00105), which was significantly higher than that in paired
      noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002, Mann
      Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374,
      quartile range, 0-0.0004225) (P=0.002, Mann-Whitney test). CONCLUSION: CD-mtDNA
      mutation plays an important role in the development and progression of HCC.

PMID- 15162526
TI  - Expression of cytochrome P4502E1 gene in hepatocellular carcinoma.
AB  - AIM: To investigate cytochrome P4502E1 (CYP2E1) gene expression in occurrence and
      progression of hepatocellular carcinoma (HCC). METHODS: The human liver arrayed
      library was spotted onto the nylon membranes to make cDNA array. Hybridization of
      cDNA array was performed with labeled probes synthesized from RNA isolated from
      HCC and adjacent liver tissues. Sprague-Dawley rats were administrated
      diethylnitrosamine (DENA) to induce HCC. CYP2E1 expression was detected by the
      method of RT-PCR and Northern blot analysis. RESULTS: CYP2E1 was found by cDNA
      array hybridization to express differently between HCC and liver tissues. CYP2E1
      only expressed in liver, but did not express in HCC tissues and expressed lowly
      in cirrhotic tissues. In the progression of cirrhosis and HCC, the expression
      level of CYP2E1 was gradually decreased and hardly detected until the late stage
      of HCC. CONCLUSION: Using arrayed library to make cDNA arrays is an effective
      method to find differential expression genes. CYP2E1 is a unique gene expressing
      in liver but did not express in HCC. CYP2E1 expression descended along with the
      initiation and progression of HCC, which is noteworthy further investigations in
      its significance in the development of HCC.

PMID- 15162527
TI  - Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma.
AB  - AIM: Signal transducers and activators of transcription (STATs) are a family of
      transcription factors activated in response to cytokines and growth factors.
      Constitutive activation of Stat3 has been observed in a growing number of tumor
      derived cell lines, as well as tumor specimens from human cancers. The purpose of
      this study was to investigate the expression of p-Stat3, activated form of Stat3,
      and its downstream mediators including cyclin D1 and Bcl-x(L) in colorectal
      carcinoma (CRC), and to explore the possible mechanism of Stat3 signaling pathway
      in the tumorigenesis of colorectal carcinoma. METHODS: Tissue samples from 45
      patients of primary colorectal carcinoma were selected for studying Stat3
      signaling pathway protein expression. Western blot analysis was used to measure
      the expression of p-Stat3, cyclin D1, and Bcl-x(L) proteins in colorectal
      carcinomas. Furthermore, the expression patterns of these proteins were analyzed
      for their distribution at the cellular level by immunohistochemical staining of
      the tissues. RESULTS: Protein levels of p-Stat3, cyclin D1, and Bcl-x(L) were
      increased in colorectal carcinomas compared with adjacent normal mucosae
      (P<0.05). Elevated levels of p-Stat3 were correlated with the nodal metastasis
      and the stage (P<0.05). Overexpression of cyclin D1 was associated with the nodal
      metastasis (P<0.05). There was also a significant correlation between the
      expressions of p-Stat3 and cyclin D1 (r=0.382, P<0.05). CONCLUSION: Constitutive
      activation of Stat3 may play an important role in the tumorigenesis of colorectal
      carcinoma, and the detailed mechanism of Stat3 signaling pathway in CRC deserves
      further investigation.

PMID- 15162528
TI  - Postprocessing techniques of CT colonography in detection of colorectal
      carcinoma.
AB  - AIM: To evaluate the value of postprocessing techniques of CT colonography,
      including multiplanar reformation (MPR), virtual colonoscopy (VC), shaded surface
      display (SSD) and Raysum, in detection of colorectal carcinomas. METHODS: Sixty
      four patients with colorectal carcinoma underwent volume scanning with spiral CT.
      MPR, VC, SSD and Raysum images were obtained by using four kinds of
      postprocessing techniques in workstation. The results were comparatively analyzed
      according to circumferential extent, lesion length and pathology pattern of
      colorectal carcinomas. All diagnoses were proved pathologically and surgically.
      RESULTS: The accuracy of circumferential extent of colorectal carcinoma
      determined by MPR, VC, SSD and Raysum was 100.0%, 82.8%, 79.7% and 79.7%,
      respectively. There was a significant statistical difference between MPR and VC.
      The consistent rate of lesion length was 89.1%, 76.6%, 95.3% and 100.0%,
      respectively. There was a statistical difference between VC and SSD. The accuracy
      of discriminating pathology pattern was 81.3%, 92.2%, 71.9% and 71.9%,
      respectively. There was a statistical difference between VC and SSD. MPR could
      determine accurately the circumference of colorectal carcinoma, Raysum could
      determine the length of lesion more precisely than SSD, VC was helpful in
      discriminating pathology patterns. CONCLUSION: MPR, VC, SSD and Raysum have
      advantage and disadvantage in detection of colorectal carcinoma, use of these
      methods in combination can disclose the lesion more accurately.

PMID- 15162529
TI  - Dendritic cells from chronic hepatitis B patients can induce HBV antigen-specific
      T cell responses.
AB  - AIM: To determine whether dendritic cells (DCs) from chronic hepatitis B patients
      could induce HBV antigen-specific T cell responses or not. METHODS: DCs were
      generated from peripheral blood mononuclear cells of patients with chronic
      hepatitis B (CHB) infection and healthy donors. We compared the phenotypes of
      these DCs and their ability to secrete cytokines and to participate in mixed
      lymphocyte reactions. In addition, autologous lymphocytes were cultured with DCs
      loaded with HBV core region peptide HBcAg8-27, an epitope recognized by cytotoxic
      T lymphocytes (CTL), and bearing human leucocyte antigen (HLA)-A2 for 10 d.
      Cytokine secretion and lytic activity against peptide-pulsed target cells were
      assessed. RESULTS: DCs with typical morphology were generated successfully by
      culturing peripheral blood mononuclear cells (PBMCs) from CHB patients with AIM-V
      containing GM-CSF and IL-4. Compared with DCs from normal donors, the level of
      CD80 expressed in DCs from CHB patients was lower, and DCs from patients had
      lower capacity of stimulate T cell proliferation. When PBMCs isolated from
      patients with chronic or acute hepatitis B infection and from normal donors were
      cocultured with HBcAg18-27 peptide, the antigen-specific memory response of PBMCs
      from acute hepatitis B patients was stronger than that of PBMCs from chronic
      hepatitis B patients or normal donors. PBMCs cocultured with DCs treated with
      HBcAg18-27 CTL epitope peptide induced an antigen-specific T cell reaction, in
      which the level of secreted cytokines and lytic activity were higher than those
      produced by memory T cells. CONCLUSION: DCs from patients with CHB can induce HBV
      antigen-specific T cell reactions, including secretion of cytokines essential for
      HBV clearance and for killing cells infected with HBV.

PMID- 15162530
TI  - Selection of a peptide mimicking neutralization epitope of hepatitis E virus with
      phage peptide display technology.
AB  - AIM: To select the peptide mimicking the neutralization epitope of hepatitis E
      virus which bound to non-type-specific and conformational monoclonal antibodies
      (mAbs) 8C11 and 8H3 fromed 7-peptide phage display library, and expressed the
      peptide recombinant with HBcAg in E.coli, and to observe whether the recombinant
      HBcAg could still form virus like particle (VLP) and to test the activation of
      the recombinant polyprotein and chemo-synthesized peptide that was selected by
      mAb 8H3. METHODS: 8C11 and 8H3 were used to screen for binding peptides through a
      7-peptide phage display library. After 4 rounds of panning, monoclonal phages
      were selected and sequenced. The obtained dominant peptide coding sequences was
      then synthesized and inserted into amino acid 78 to 83 of hepatitis B core
      antigen (HBcAg), and then expressed in E.coli. Activity of the recombinant
      proteins was detected by Western blotting, VLPs of the recombinant polyproteins
      were tested by transmission electron microscopy and binding activity of the chemo
      synthesized peptide was confirmed by BIAcore biosensor. RESULTS: Twenty-one
      positive monoclonal phages (10 for 8C11, and 11 for 8H3) were selected and the
      inserted fragments were sequenced. The DNA sequence coding for the obtained
      dominant peptides 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 the HBcAg vector, then expressed in E.coli. The recombinant proteins
      aggregated into homodimer or polymer on SDS-PAGE, and could bind to mAb 8C11 and
      8H3 in Western blotting. At the same time, the recombinant polyprotein could form
      virus like particles (VLPs), which could be visualized on electron micrograph.
      The dominant peptide 8H3A selected by mAb 8H3 was further chemo-synthesized, and
      its binding to mAb 8H3 could be detected by BIAcore biosensor. CONCLUSION: These
      results implicate that conformational neutralizing epitope can be partially
      modeled by a short peptide, which provides a feasible route for subunit vaccine
      development.

PMID- 15162532
TI  - Modulation of human enteric epithelial barrier and ion transport function by
      Peyer's patch lymphocytes.
AB  - AIM: To investigate the role of Peyer's patch lymphocytes in the regulation of
      enteric epithelial barrier and ion transport function in homeostasis and host
      defense. METHODS: Mouse Peyer's patch lymphocytes were co-cultured with human
      intestinal epithelial cell line Caco-2 either in the mixed or separated (isolated
      but permeable compartments) culture configuration. Barrier and transport
      functions of the Caco-2 epithelial monolayers were measured with short-circuit
      current (Isc) technique. Release of cytokines was measured by enzyme-linked
      immunosorbent assay (ELISA) and cytokine mRNA expression was analyzed by semi
      quantitative RT-PCR. Barrier and iontransport functions of both culture
      conditions following exposure to Shigella lipopolysaccharide (LPS) were also
      examined. RESULTS: The transepithelial resistance (TER) of the epithelial
      monolayers co-cultured with Peyer's patch lymphocytes was maintained whereas that
      of the Caco-2 monolayers alone significantly decreased after eight days in
      culture. The forskolin-induced anion secretion, in either absence or presence of
      LPS, was significantly suppressed in the both co-cultures as compared with the
      Caco-2 cells alone. Furthermore, only the mixed co-culture condition induced the
      expression and release of mIL-6 from Peyer's patch lymphocytes, which could be
      further enhanced by LPS. However, both co-culture conditions suppressed
      expression and release of epithelial hIL-8 under the unstimulated conditions,
      while the treatment with LPS stimulated their hIL-8 expression and release.
      CONCLUSION: Peyer's patch lymphocytes may modulate intestinal epithelial barrier
      and ion transport function in homeostasis and host defense via cell-cell contact
      and cytokine signaling.

PMID- 15162531
TI  - Community-based survey of HCV and HIV coinfection in injection drug abusers in
      Sichuan Province of China.
AB  - AIM: To investigate the prevalence and risk factors of HCV/HIV coinfection in
      injection drug abusers (IDAs) in Lianshan Yi Autonomous Prefecture of Sichuan
      province, China. METHODS: From November 8, 2002 to November 29, 2002, a community
      based survey was conducted to investigate the demographic characteristics,
      patterns of shared injectors devices and sexual behaviors in IDAs. Blood samples
      were also collected to test HCV and HIV infection. A total of 379 subjects were
      recruited in the study through community outreach and peer recruiting methods.
      RESULTS: Of the 379 IDAs, the HCV prevalence and HIV prevalence were 71.0% and
      11.3%, respectively, and HCV/HIV coinfection was 11.3%. HCV infection was found
      in 100% and 67.3% of HIV-positive and HIV-negative IDAs, respectively. HIV
      prevalence was 16.0% in HCV positive IDAs while none of the HCV negative IDAs was
      positive for HIV. Ethnicity, shared needles or syringes and cotton in the past 3
      mo and syphilis infection were associated with HCV/HIV coinfection shown by
      univariate analysis using chi-square test. Multivariate logistic regression
      analysis showed that shared needles or syringes in the past 3 mo (Odds
      ratio=3.121, 95% CI: 1.278-7.617, P<0.05) and syphilis infection (Odds
      ratio=2.914, 95% CI: 1.327-6.398, P<0.01) were significantly associated with HCV
      infection. No statistically significant association was found in univariate
      analysis between sexual behaviors and HCV/HIV coinfection. CONCLUSION: Shared
      needles and syringes in the past 3 mo and syphilis infection were significantly
      associated with HCV infection. Further sero-epidemiological prospective cohort
      studies should be conducted to clarify the impact of syphilis and high risk
      sexual behaviors on HCV transmission through unprotected sexual intercourse.

PMID- 15162533
TI  - Association of differentially expressed genes with activation of mouse hepatic
      stellate cells by high-density cDNA microarray.
AB  - AIM: To characterize the gene expression profiles associated with activation of
      mouse hepatic stellate cell (HSC) and provide novel insights into the
      pathogenesis of hepatic fibrosis. METHODS: Mice HSCs were isolated from BALB/c
      mice by in situ perfusion of collagenase and pronase and single-step density
      Nycodenz gradient. Total RNA and mRNA of quiescent HSC and culture-activated HSC
      were extracted, quantified and reversely transcribed into cDNA. cDNAs from
      activated HSC were labeled with Cy5 and cDNAs from the quiescent HSC were labeled
      with Cy3, which were mixed with equal quantity, then hybridized with cDNA chips
      containing 4000 genes. Chips were washed, scanned and analyzed. Increased
      expression of 4 genes and decreased expression of one gene in activated HSC were
      confirmed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A
      total of 835 differentially expressed genes were identified by cDNA chip between
      activated and quiescent HSC, and 465 genes were highly expressed in activated
      HSC. The differentially expressed genes included those involved in protein
      synthesis, cell-cycle regulation, apoptosis, and DNA damage response. CONCLUSION:
      Many genes implicated in intrahepatic inflammation, fibrosis and proliferation
      were up-regulated in activated HSC. cDNA microarray is an effective technique in
      screening for differentially expressed genes between two different situations of
      the HSC. Further analysis of the obtained genes will help understand the
      molecular mechanism of activation of HSC and hepatic fibrosis.

PMID- 15162534
TI  - Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells.
AB  - AIM: To investigate the importance of direct contact between Kupffer cells (KCs)
      and hepatocytes (HCs) during hepatic inflammatory responses, and the effect of
      leflunomide's active metabolite, A(771726), on cytokines in KCs, HCs and KC
      cocultures (DC cocultures). METHODS: KCs and HCs in liver were isolated by
      digestion with pronase and collagenase. Lipopolysaccharide (LPS)-induced
      inflammatory response in monocultures of rat HCs and KCs was compared with that
      in DC cocultures. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL
      1) concentrations in different culture supernatants were measured with ELISA. TNF
      alpha mRNA in KCs of inflammatory liver injury was analyzed with reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: DC cocultures strongly
      exhibited the production of TNF-alpha and IL-1 compared with other cultures, and
      these cytokines were mainly produced by KCs, especially by activated KCs. Time
      course studies revealed an increased production of TNF-alpha preceding the IL-1
      production, suggesting that increased TNF-alpha levels could be involved in the
      increase of IL-1 production. Leflunomide's active metabolite, A(771726), had
      significantly inhibitory effect on TNF-alpha and IL-1 at protein and
      transcription levels, and the reduced production of IL-1 by A(771726) was
      associated with the inhibitory action of A(771726 ) on TNF-alpha. CONCLUSION:
      Leflunomide can inhibit hepatocyte damage by inhibiting proinflammatory cytokine
      release from KCs.

PMID- 15162535
TI  - A rapid and efficient method to express target genes in mammalian cells by
      baculovirus.
AB  - AIM: To investigate the modification of baculovirus vector and the feasibility of
      delivering exogenous genes into mammalian cells with the culture supernatant of
      Spodoptera frugiperta (Sf9) cells infected by recombinant baculoviruses. METHODS:
      Two recombinant baculoviruses (BacV-CMV-EGFPA, BacV-CMV-EGFPB) containing CMV
      EGFP expression cassette were constructed. HepG2 cells were directly incubated
      with the culture supernatant of Sf9 cells infected by recombinant baculoviruses,
      and reporter gene transfer and expression efficiencies were analyzed by flow
      cytometry (FCM). The optimal transduction conditions were investigated by FCM
      assay in HepG2 cells. Gene-transfer and expression efficiencies in HepG2 or CV1
      cells by baculovirus vectors were compared with lipofectAMINE, recombinant
      retrovirus and vaccinia virus expression systems. Twenty different mammalian cell
      lines were used to investigate the feasibility of delivering exogenous genes into
      different mammalian cells with the culture supernatant of infected Sf9 cells.
      RESULTS: CMV promoter could directly express reporter genes in Sf9 cells with a
      relatively low efficiency. Target cells incubated with the 1:1 diluted culture
      supernatant (moi=50) for 12 h at 37 degrees C could achieve the highest
      transduction and expression efficiencies with least impairment to cell viability.
      Under similar conditions the baculovirus vector could achieve the highest gene
      transfer and expression efficiency than lipofectAMINE, recombinant retrovirus and
      vaccinia virus expression systems. Most mammalian cell lines could be transduced
      with recombinant baculovirus. In primate adherent culture cells the recombinant
      baculovirus could arrive the highest infection and expression efficiencies, but
      it was not very satisfactory in the cell lines from mice and suspended culture
      cells. CONCLUSION: Mammalian cells incubated with the culture supernatant of
      infected Sf9 cells could serve as a very convenient way for rapid and efficient
      expression of foreign genes in mammalian cells, but it might be more suitable for
      primate adherent culture cells.

PMID- 15162536
TI  - Risk factors of development of gut-derived bacterial translocation in thermally
      injured rats.
AB  - AIM: Studies have demonstrated that gut-derived bacterial translocation (BT)
      might play a role in the occurrence of sepsis and multiple organ dysfunction
      syndrome (MODS). Yet, no convincing overall analysis of risk factors for BT has
      been reported. The purpose of this study was to evaluate the related factors for
      the development of BT in burned rats. METHODS: Wistar rats were subjected to 30%
      third-degree burns. Then samples were taken on postburn d 1, 3, and 5. Incidence
      of BT and counts of mucosal bifidobacteria, fungi and E. coli, mucus sIgA, degree
      of injury to ileal mucosa, and plasma interleukin-6 were observed. Univariate
      analysis and multivariate logistic regression analysis were performed. RESULTS:
      The overall BT rate was 53.9% (69 in 128). The result of univariate analysis
      showed that the levels of plasma endotoxin and interleukin-6, the counts of
      mucosal fungi and E. coli, and the scores of ileum lesion were markedly increased
      in animals with BT compared with those without (P=0.000-0.005), while the levels
      of mucus sIgA and the counts of mucosal bifidobacteria were significantly reduced
      in animals with translocation compared with those without (P=0.000). There was a
      significant positive correlation between mucus sIgA and the counts of mucosal
      bifidobacteria (r=0.74, P=0.001). Moreover, there were strong negative
      correlations between scores of ileum-lesion and counts of bifidobacteria (r=
      0.67, P=0.001). Multivariate logistic regression revealed that ileum lesion score
      (odds ratio [OR] 45.52, 95% confidence interval [CI] 5.25-394.80), and counts of
      mucosal bifidobacteria (OR 0.039, 95% CI 0.0032-0.48) were independent predictors
      of BT secondary to severe burns. CONCLUSION: Ileal lesion score and counts of
      mucosal bifidobacteria can be chosen as independent prognosis factors of the
      development of BT. Specific interventions targeting these high-risk factors might
      be implemented to attenuate BT, including strategies for repair of damaged
      intestinal mucosae and restoration of the balance of gastrointestinal flora.

PMID- 15162537
TI  - Gene expression profiles of hepatocytes treated with La(NO3)3 of rare earth in
      rats.
AB  - AIM: To compare the gene expression between La(NO(3))(3)-exposed and control rats
      in vivo. METHODS: Rats were fed La(NO(3))(3) once daily at a dose of 20 mg/kg for
      one month by gavage. Gene expression of hepatocytes was detected using mRNA
      differential display (DD) technique and cDNA microarray and compared between
      treated and control groups. RESULTS: Six differentially expressed sequence tags
      were cloned by DD, of which five were up regulated and one was down regulated in
      treated rats. Two sequences were determined. One band was novel. The other shared
      100% sequence homology with AU080263 Sugano mouse brain mncb Mus musculus cDNA
      clone MNCb-5435 5'. With DNA microarray, 136 differentially expressed genes were
      identified including 131 over-expressed genes and 5 under-expressed genes. Most
      of these differentially expressed genes were cell signal and transmission genes,
      genes associated with metabolism, protein translation and synthesis. CONCLUSION:
      La(NO(3))(3) could change the expression levels of some kinds of genes. Further
      analysis of the differentially expressed genes would be helpful for understanding
      the wide biological effect spectrum of rare earth elements.

PMID- 15162538
TI  - Competitive inhibition of adherence of enterotoxigenic Escherichia coli,
      enteropathogenic Escherichia coli and Clostridium difficile to intestinal
      epithelial cell line Lovo by purified adhesin of Bifidobacterium adolescentis
      1027.
AB  - AIM: To observe competitive inhibition of adherence of enterotoxigenic
      Escherichia coli (ETEC), enteropathogenic Escherichia coli (EPEC) and Clostridium
      difficile (C. difficile) to intestinal epithelial cell line Lovo by purified
      adhesin of Bifidobacterium adolescentis 1027 (B. ado 1027). METHODS: The binding
      of bacteria to intestinal epithelial cell line Lovo was counted by adhesion
      assay. The inhibition of adherence of ETEC, EPEC and C. difficile to intestinal
      epithelial cell line Lovo by purified adhesin of B. ado 1027 was evaluated
      quantitatively by flow cytometry. RESULTS: The purified adhesin at the
      concentration of 10 microg/mL, 20 microg/mL and 30 microg/mL except at 1
      microg/mL and 5 microg/mL could inhibit significantly the adhesion of ETEC, EPEC
      and C. difficile to intestinal epithelial cell line Lovo. Moreover, we observed
      that a reduction in bacterial adhesion was occurred with increase in the
      concentration of adhesin, and MFI (Mean fluorescent intensity) was decreased with
      increase in the concentration of adhesin. CONCLUSION: The purified adhesin of B.
      ado 1027 can inhibit the adhesion of ETEC, EPEC and C. difficile to intestinal
      epithelial cell line Lovo in a dose-dependent manner.

PMID- 15162540
TI  - Imaging diagnosis of 12 patients with hepatic tuberculosis.
AB  - AIM: To assess CT, MR manifestations and their diagnostic value in hepatic
      tuberculosis. METHODS: CT findings in 12 cases and MR findings in 4 cases of
      hepatic tuberculosis proved by surgery or biopsy were retrospectively analyzed.
      RESULTS: (1) CT findings: One case of serohepatic type of hepatic tuberculosis
      had multiple-nodular lesions in the subcapsule of liver. Parenchymal type was
      found in 10 cases, including multiple, miliary, micronodular and low-density
      lesions with miliary calcifications in 2 cases; singular, low-density mass with
      multiple flecked calcifications in 3 cases; multiple cystic lesions in 1 case;
      multiple micronodular and low-density lesions fusing into multiloculated cystic
      mass or "cluster" sign in 3 cases; and singular, macronodular and low-density
      lesion with multiple miliary calcifications in 1 case. One case of tuberculous
      cholangitis showed marked dilated intrahepatic ducts with multiple flecked
      calcifications in the porta hepatis. (2) MR findings in 4 cases were hypointense
      on both T1-weighted imagings and T2-weighted imagings in one case, hypointense on
      T1-weighted imagings and hyperintense on T2-weighted imagings in 3 cases.
      Enhanced MR in 3 cases was slightly shown peripheral enhancement or with
      multilocular enhancement. CONCLUSION: Various types of hepatic tuberculosis have
      different imaging findings, and typical CT and MR findings can suggest the
      diagnosis.

PMID- 15162539
TI  - Blockage of transforming growth factor beta receptors prevents progression of pig
      serum-induced rat liver fibrosis.
AB  - AIM: To test the hypothesis that introduction of antisense T beta R I and T beta
      R II eukaryotic expressing plasmids into a rat model of immunologically induced
      liver fibrosis might block the action of TGF-beta (1) and halt the progression of
      liver fibrosis. METHODS: RT-Nest-PCR and gene recombination techniques were used
      to construct rat antisense T beta R I and T beta R II recombinant plasmids which
      could be expressed in eukaryotic cells. The recombinant plasmids and empty vector
      (pcDNA3) were encapsulated by glycosyl-poly-L-lysine and then transducted into
      rats of pig serum-induced liver fibrosis model. Expression of exogenously
      transfected gene was assessed by Northern blot, and hepatic expressions of T beta
      R I and T beta R II were evaluated by RT-PCR and Western blot. We also performed
      ELISA for serum TGF-beta(1), hydroxyproline of hepatic tissues,
      immunohistochemistry for collagen types I and III, and VG staining for
      pathological study of the liver tissues. RESULTS: The exogenous antisense T beta
      R I and T beta R II plasmids could be well expressed in vivo, and block mRNA and
      protein expression of T beta R I and T beta R II in the fibrotic liver at the
      level of mRNA respectively. These exogenous plasmid expressions reduced the level
      of TGF-beta(1) (antisense T beta R I group 23.998+/-3.045 ng/mL, antisense T beta
      R II group 23.156+/-3.131 ng/mL, disease control group 32.960+/-3.789 ng/mL;
      F=38.19, 36.73, P<0.01). Compared with disease control group, the contents of
      hepatic hydroxyproline (antisense T beta R I group 0.169+/-0.015 mg/g liver,
      antisense T beta R II group 0.167+/-0.009 mg/g liver, disease control group
      0.296+/-0.026 mg/g liver; F=14.39, 15.48, P<0.01) and the deposition of collagen
      types I and III decreased in the two antisense treatment groups (antisense T beta
      R I group, collagen type I 669.90+/-50.67, collagen type III 657.29+/-49.48;
      antisense T beta R II group, collagen type I 650.26+/-51.51, collagen type III
      661.58+/-55.28; disease control group, collagen type I 1209.44+/-116.60, collagen
      type III 1175.14+/-121.44; F=15.48 to 74.89, P<0.01). Their expression also
      improved the pathologic classification of liver fibrosis models (compared with
      disease control group, chi(2)=17.14, 17.24, P<0.01). No difference was found in
      the level of TGF-beta(1), the contents of hepatic hydroxyproline and collagen
      types I and III and pathologic grade between pcDNA3 control group and disease
      control group or between the two antisense treatment groups (F=0.11 to 1.06,
      chi(2)=0.13 to 0.16, P>0.05). CONCLUSION: Antisense T beta R I and T beta R II
      recombinant plasmids have certain reverse effects on liver fibrosis and can be
      used as possible candidates for gene therapy.

PMID- 15162541
TI  - Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and
      controls.
AB  - AIM: Tumor formation is generally linked to an expansion of glycolytic
      phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor
      cells generally overexpress a special glycolytic isoenzyme, termed pyruvate
      kinase type M(2). The present study was designed to evaluate the use of a new
      tumor marker, tumor M(2)-PK, in discriminating gastrointestinal cancer patients
      from healthy controls, and to compare with the reference tumor markers CEA and
      CA72-4. METHODS: The concentration of tumor M(2)-PK in body fluids could be
      quantitatively determined by a commercially available enzyme-linked immunosorbent
      assay (ELISA)-kit (ScheBo Tech, Giessen, Germany). By using this kit, the tumor
      M(2)-PK concentration was measured in EDTA-plasma of 108 patients. For the
      healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded
      to 90% specificity. Overall 108 patients were included in this study, 54 patients
      had a histological confirmed gastric cancer, 54 patients colorectal cancer, and
      20 healthy volunteers served as controls. RESULTS: The cut-off value to
      discriminate patients from controls was established at 15 U/mL for tumor M(2)-PK.
      The mean tumor M(2)-PK concentration of gastric cancer was 26.937 U/mL. According
      to the TNM stage system, the mean tumor M(2)-PK concentration of stage I was
      16.324 U/mL, of stage II 15.290 U/mL, of stage III 30.289 U/mL, of stage IV
      127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The
      mean Tumor M(2)-PK concentration of colorectal cancer was 30.588 U/mL. According
      to the Dukes stage system, the mean tumor M(2)-PK concentration of Dukes A was
      16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/ml, of non
      metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M(2)-PK
      concentration allowed a significant discrimination of colorectal cancers (30.588
      U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from
      controls (10.965 U/mL) (P<0.05). The overall sensitivity of tumor M(2)-PK for
      colorectal cancer was 68.52%, while that of CEA was 43.12%. In gastric cancer,
      tumor M(2)-PK showed a high sensitivity of 50.47%, while CA72-4 showed a
      sensitivity of 35.37%. CONCLUSION: Tumor M(2)-PK has a higher sensitivity than
      markers CEA and CA72-4, and is a valuable tumor marker for the detection of
      gastrointestinal cancer.

PMID- 15162542
TI  - Epidemiology of gastroesophageal reflux disease: a general population-based study
      in Xi'an of Northwest China.
AB  - AIM: Gastroesophageal reflux disease (GERD) is a common disorder in the Western
      population, but detailed population-based data in China are limited. The aim of
      this study was to understand the epidemiology of symptomatic gastroesophageal
      reflux (SGER) in adults of Xi'an, a northwestern city of China, and to explore
      the potential risk factors of GERD. METHODS: Symptoms suggestive of GERD,
      functional dyspepsia (FD), irritable bowel syndrome (IBS), upper respiratory
      diseases and some potential risk factors were investigated in a face-to-face
      manner in a region-stratified random samples of 2789 residents aged 18-70 years
      in Xi'an by using a standardized questionnaire. METHODS: With a response rate of
      91.8%, the prevalence of SGER was 16.98% (95% CI, 14.2-18.92) in Xi'an adults,
      and no gender-related difference was observed (P<0.05). SGER was more common
      among subjects aged 30-70 years than in those aged 18-29 years (P<0.01). The
      prevalence of SGER in rural, urban and suburban subjects was 21.07%, 17.44% and
      12.12%, respectively, and there was a significant difference between rural, urban
      and suburban regions (P<0.05). Compared with subjects without SGER, the
      prevalence of symptoms suggestive of FD and IBS, pneumonia, asthma, bronchitis,
      laryngitis, pharyngitis, chronic cough, wheeze, globus sensation, oral ulcer and
      snore was significantly increased in subjects with SGER (P<0.01). Heavy smoking
      (OR=5.76; CI, 3.70-6.67), heavy alcohol use (OR=2.85; CI, 1.67-4.49), peptic
      ulcer (OR=5.76; CI, 3.99-8.32), cerebral palsy (OR=3.97; CI, 1.97-8.00),
      abdominal operation (OR=2.69; CI, 1.75-4.13), obesity (OR=2.16; CI, 1.47-3.16),
      excessive food intake (OR=1.43; CI, 1.17-1.15), sweet food (OR=1.23; CI, 0.89
      1.54), and consumption of coffee (OR=1.23; CI, 0.17-2.00) were independently
      associated with SGER. The episodes of GERD were commonly precipitated by dietary
      factors (66.05%), followed by body posture (26.54%), ill temper (23.72%), fatigue
      (22.32%) and stress (10.93%). CONCLUSION: GERD is common in Xi'an's adult
      population with a mild or moderate degree. The etiology and pathogenesis of GERD
      are probably associated with FD, IBS, and some respiratory, laryngopharyngeal and
      odontostological diseases or symptoms. Some lifestyles, diseases and dietary
      factors are the risk factors of GERD.

PMID- 15162543
TI  - Serum hepatic enzyme manifestations in patients with severe acute respiratory
      syndrome: retrospective analysis.
AB  - AIM: To evaluate the hepatic function in patients with severe acute respiratory
      syndrome (SARS) and possible causes of hepatic disorder in these patients.
      METHODS: One hundred and eighty-two patients with SARS were employed in a
      retrospective study that investigated hepatic dysfunction. Liver alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase
      (LDH) were analyzed in these patients. Patients with different hospital
      treatments were further investigated. RESULTS: Of the 182 patients, 128(70.3%)
      had abnormal ALT activity, 57(31.3%) had abnormal AST activity and 87(47.8%) had
      abnormal LDH activity. The peak of elevated hepatic enzyme activities occurred
      between the sixth day and the tenth day after the first day of reported fever. Of
      the 182 patients, 160(87.9%) had been treated with antibiotics, 137(75.2%) with
      Ribavirin, and 115(63.2%) with methylpredisolone. There was no statistically
      significant correlation between the duration of Ribavirin treatment and hepatic
      dysfunction. CONCLUSION: Abnormal liver functions were common in patients with
      SARS and could be associated with virus replication in the liver.

PMID- 15162544
TI  - Maastricht II treatment scheme and efficacy of different proton pump inhibitors
      in eradicating Helicobacter pylori.
AB  - AIM: The Maastricht II criteria suggest the use of amoxicillin and clarithromycin
      in addition to a proton pump inhibitor over 7-10 d as a first line therapy in the
      eradication of Helicobacter pylori (H pylori). For each proton pump inhibitor,
      various rates of eradication have been reported. The present study was to compare
      the efficacy of different proton pump inhibitors like omeprazole, lansoprazole
      and pantoprazole in combination with amoxicillin and clarithromycin in the first
      line eradication of H pylori and to investigate the success of H pylori
      eradication in our district. METHODS: A total of 139 patients were included
      having a Helicobacter pylori (+) gastroduodenal disorders diagnosed by means of
      histology and urease test. Besides amoxicillin (1000 mg twice a day) and
      clarithromycin (500 mg twice a day), they were randomized to take omeprazole (20
      mg twice a day), or lansoprazole (30 mg twice a day), or pantoprozole (40 mg
      twice a day) for 14 d. Four weeks after the therapy, the eradication was assessed
      by means of histology and urease test. It was evaluated as eradicated if the H
      pylori was found negative in both. The complaints (pain in epigastrium, nocturnal
      pain, pyrosis and bloating) were graded in accordance with the Licert scale. The
      compliance of the patients was recorded. RESULTS: The eradication was found to be
      40.8% in the omeprazole group, 43.5% in the lansoprazole group and 47.4% in the
      pantoprazole group. Sixty-three out of 139 patients (45%) had eradication. No
      statistically significant difference was observed between the groups. Significant
      improvements were seen in terms of the impact on the symptom scores in each
      group. CONCLUSION: There was no difference between omeprazole, lansoprazole and
      pantoprazole in H pylori eradication, and the rate of eradication was as low as
      45%. Symptoms were improved independent of the eradication in each treatment
      group. The low eradication rates suggest that the antibiotic resistance or the
      genetic differences of the microorganism might be in effect. Further studies are
      required to verify these suggestions.

PMID- 15162545
TI  - Liver regional continuous chemotherapy: use of femoral or subclavian artery for
      percutaneous implantation of catheter-port systems.
AB  - AIM: To evaluate the feasibility and safety of the intraarterial chemotherapy of
      the liver cancer by an interventional method, catheter-port system. METHODS:
      Thirty-two catheter-port systems were implanted percutaneously via the femoral
      artery or subclavian artery. Chemotherapies were performed 0-5 d after the
      implantation of the catheter-port systems. The mean interval between two
      sequential chemotherapies was 4 wk. The occurrence of side effects of the
      implantation was examined clinically. RESULTS: Implantation of the catheter-port
      was successful in all patients. Mean patency period was 210 d. One occlusion
      (3.1%) of the catheter was observed. Displacement of the catheter was observed in
      one case (3.1%). One patient rated a hematoma in the chest wall as important.
      Mild hematoma was reported in 8 cases (25%). In 3 of 32 cases (9.4%), mild pain
      was reported initially, and dysesthesia was reported in seven (21.9%). No patient
      rated overall discomfort as mild, severe, or important. CONCLUSION: Percutaneous
      placement is feasible and safe for liver regional continuous chemotherapy.
      Compared with surgical placement, the overall complication rate is comparable or
      less.

PMID- 15162546
TI  - Expression of subtypes of somatostatin receptors in hepatic stellate cells.
AB  - AIM: To elucidate the mechanism by which somatostatin and its analogue exert the
      influence on liver fibrosis, and to investigate the mRNA expression of
      somatostatin receptors subtypes (SSTRs) and the distribution of somatostatin
      analogue octreotide in rat hepatic stellate cells (HSCs). METHODS: HSCs were
      isolated from Sprague Dawley (SD) rats by in situ perfusion and density gradient
      centrifugation. After several passages, the mRNA expression of 5 subtypes of
      SSTRs were assessed by reverse transcription-polymerase chain reaction (RT-PCR).
      HSCs were planted on coverslip and co-cultured with octreotide tagged by FITC.
      Then the distribution of FITC fluorescence was observed under laser scanning
      confocal microscope (LSCM) in 12-24 h. RESULTS: There were mRNA expression of
      SSTR2, SSTR3 and SSTR5 but not SSTR1 and SSTR4 in SD rat HSCs. The mRNA
      expression level of SSTR2 was significantly higher than that of other subtypes
      (P<0.01). FITC fluorescence of octreotide was clearly observed on the surface and
      in the cytoplasm, but not in the nuclei of HSCs under LSCM. CONCLUSION: The
      effect exerted by somatostatin and its analogues on HSCs may mainly depend on the
      expression of SSTR2, SSTR3 and SSTR5. Octreotide can perfectly combine with HSCs,
      and thereby exerts its biological activity on regulating the characters of active
      HSCs. This provides a potential prevention and management against liver fibrosis.

PMID- 15162547
TI  - Filamentous-actins in human hepatocarcinoma cells with CLSM.
AB  - AIM: To establish a method for optical sections of HepG2 human hepatoblastoma
      cells with confocal laser scanning microscope (CLSM) and to study the spatial
      structure of filamentous actin (F-actin) in HepG2 cells. METHODS: HepG2 cells
      were stained with FITC-phalloidin that specifically binds F-actin, with propidium
      iodide (PI) to the nucleus, and scanned with a CLSM to generate optically
      sectioned images. A series of optical sections taken successively at different
      focal levels in steps of 0.7 microm were reconstructed with the CLSM
      reconstruction program. RESULTS: CLSM images showed that the FITC-stained F-actin
      was abundant microfilament bundles parallel or netted through the whole cell and
      its processes. Most F-actin microfilaments extended through the cell from one
      part toward the other or run through the process. Some microfilaments were
      attached to the plasma membrane, or formed a structural bridge connecting to the
      neighboring cells. CONCLUSION: A method for double labeling HepG2 human
      hepatoblastoma cells and CLSM imaging F-actin microfilaments and nuclei by image
      thin optical sections and spatial structure was developed. It provides a very
      useful way to study the spatial structure of F-actin.

PMID- 15162548
TI  - Effect of intraoperative radiotherapy combined with external beam radiotherapy
      following internal drainage for advanced pancreatic carcinoma.
AB  - AIM: To determine the survival of advanced pancreatic cancer patients treated
      with intraoperative radiotherapy (IORT) combined with external beam radiation
      therapy (EBRT) following internal drainage (cholecystojejunostomy or
      choledochojejunostomy). METHODS: Eighty-one patients with advanced pancreatic
      cancer who received IORT combined with EBRT following internal drainage (ID)
      between 1996 and 2001 were retrospectively analyzed. Among the 81 patients, 18
      underwent ID+IORT, 25 ID+IORT+EBRT (meanwhile, given 5-Fu 300 mg/m(2) i.v. drip,
      2f/w), 16 EBRT, 22 had undergone simple internal drainage. The IORT dose was 15
      25Gy in a single fraction. The usual EBRT dose was 30-40Gy with a daily fraction
      of 1.8-2.0 Gy. RESULTS: The complete remission rate, partial remission rate of
      patients with backache and abdominal pain treated with ID+IORT were 55.5%, 33.3%
      respectively. Alleviation of pain was observed 2 or 3 wk after IORT. The median
      survival time (MST) of ID+IORT group was 10.7 mo. The pain remission rate of
      patients treated with ID+IORT+EBRT was 92%, and their MST was 12.2 mo. The MST of
      patients treated with EBRT and simple internal drainage was 5.1 mo and 7.0 mo,
      respectively. The survival curve of ID+IORT group and ID+IORT+EBRT group was
      significantly better than that of EBRT group (P<0.05). The difference between the
      ID+IORT+EBRT group and ID group was significant (P<0.05). CONCLUSION: IORT
      combined with EBRT following internal drainage can alleviate pain, improve
      quality of life and prolong survival time of patients with advanced pancreatic
      cancer.

PMID- 15162549
TI  - Effects of mu and kappa opioid receptor agonists and antagonists on contraction
      of isolated colon strips of rats with cathartic colon.
AB  - AIM: To study the effects of mu and kappa opioid receptor agonists and
      antagonists on the isolated colon strips of rats with cathartic colon. METHODS:
      Cathartic colon model was established by feeding rats with contact laxatives, and
      effects of mu and kappa opioid receptor agonists and antagonists on electricity
      stimulated contraction of isolated colon strips of rats with cathartic colon were
      observed. RESULTS: Compared with control group, exogenous mu and kappa agonists
      inhibited significantly electricity-stimulated contraction of strips of cathartic
      colon (8.50+/-0.89 mm, 6.24+/-0.91 mm, 3.35+/-0.6 mm vs 11.40+/-0.21 mm P<0.01;
      8.98+/-0.69 mm, 6.89+/-0.71 mm, 4.43+/-0.99 mm vs 11.40+/-0.21 mm, P<0.01). In
      contrast, the exogenous mu antagonist significantly enhanced electricity
      stimulated contraction of isolated colon strips (13.18+/-0.93 mm, 15.87+/-0.98
      mm, 19.46+/-1.79 mm vs 11.40+/-0.21 mm, P<0.01), but kappa antagonist had no
      effect on the isolated colon strips of rats with cathartic colon. CONCLUSION: Mu
      and kappa opioid receptors are involved in the regulation of colon motility of
      rats with cathartic colon.

PMID- 15162550
TI  - Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer.
AB  - AIM: To establish a method to detect the expression of the tumor specific growth
      factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of
      pancreatic cancer. METHODS: ELISA and Biochemical colorimetric assay were used to
      detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52
      pancreatitis patients and 96 pancreatic cancer patients. RESULTS: The positive
      likelihood ratios of TSGF, CA242 and CA19-9 were 5.4, 12.6 and 6.3, respectively,
      and their negative likelihood ratios were 0.10, 0.19 and 0.17, respectively. With
      single tumor marker diagnosed pancreatic cancer, the highest sensitivity and
      specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when
      all of them were positive, the sensitivity changed to 77.0% and the specificity
      and the positive predictive value were 100%. The levels of TSGF and CA242 were
      significantly higher in the patients with pancreatic cancer of head than those in
      the patients with pancreatic cancer of body, tail and whole pancreas, but the
      expression of CA19-9 had no correlation with the positions of the pancreatic
      cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress
      in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly
      higher than CA242 and CA19-9. CONCLUSION: The combined use of TSGF, CA242 and
      CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis.
      And it shows that it plays an important role to differentiate positions and
      tissue typing. It is a forepart diagnosis for the pancreatic cancer by
      combination checking. There is very important correlation between the three
      markers and the pancreatic cancer.

PMID- 15162551
TI  - Liver biopsy in evaluation of complications following liver transplantation.
AB  - AIM: To analyze the role of liver biopsies in differential diagnosis after liver
      transplantation. METHODS: A total of 50 biopsies from 27 patients with liver
      dysfunction out of 52 liver transplantation cases were included. Biopsies were
      obtained 0-330 d after operation, in which, 44 were fine needle biopsies, another
      6 were wedge biopsies during surgery. All tissues were stained with haemotoxylin
      eosin. Histochemical or immunohistochemical stain was done. RESULTS: The rate of
      acute rejection in detected cases and total transplantation cases was 48.2% and
      25.0%, chronic rejection rate in detected cases and total transplantation cases
      was 14.8% and 7.7%, preservation-reperfusion injury in detected cases and total
      transplantation cases was 25.9% and 13.5%, hepatic artery thrombosis rate in
      detected cases and total transplantation cases was 11.1% and 5.8%, intrahepatic
      biliary injury rate in detected cases and total transplantation cases was 7.4 %
      and 3.8%, CMV infection rate in detected cases and total transplantation cases
      was 3.7% and 1.9%, hepatitis B recurrence rate in detected cases and total
      transplantation cases was 3.7% and 1.9%, the ratio of suspicious drug-induced
      hepatic injury in detected cases and total transplantation cases was 11.1% and
      5.8%. CONCLUSION: Acute rejection and preservation-reperfusion injury are the
      major factors in early liver dysfunction after liver transplantation. Hepatic
      artery thrombosis and prolonged cold preservation may result in intrahepatic
      biliary injury. Acute rejection and viral infection may involve in the
      pathogenesis of chronic rejection. Since there are no specific lesions in drug
      induced hepatic injury, the diagnosis must closely combine clinical history and
      rule out other possible complications.

PMID- 15162555
TI  - Healing environment, Texas style.

PMID- 15162553
TI  - Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant.
AB  - We report a case of fatal liver failure due to reactivation of lamivudine
      resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic
      hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay)
      and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver
      cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA
      subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had
      increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the
      DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT
      spontaneously decreased to the former levels. On Oct 3 the patient presenting
      with general fatigue, nausea and jaundice was admitted to our hospital. The
      laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L,
      total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the
      patient and his family refused blood transfusion, plasma exchange and liver
      transplantation. The patient died 10 d after admission. The autopsy revealed
      remarkable liver atrophy.

PMID- 15162554
TI  - Brain metastasis of hepatocellular carcinoma: A case report and review of the
      literature.

PMID- 15162552
TI  - CDw75 is a significant histopathological marker for gastric carcinoma.
AB  - AIM: To study the expression of CDw75 in patients with gastric carcinoma and to
      correlate CDw75 expression with progression of the tumor. METHODS:
      Immunohistochemical method was used to examine the expression of CDw75 in 72
      cases of the gastric carcinoma and adjacent normal gastric mucosa, and the
      percentage of the cells positively stained with CDw75 was calculated using a
      computer-aided microscopic image analysis system. RESULTS: CDw75 was not
      expressed in normal gastric mucosa but detected in 37 of the 72 neoplastic
      gastric lesions. The expression of CDw75 was associated with the tumor
      progression as indicated by its close correlation with the depth of the tumor
      infiltration (chi(2)=18.415, P<0.01), TNM stage (chi(2)=10.419, P<0.05) and lymph
      node metastasis (chi(2)=6.675, P<0.01). The overall survival rate of the patients
      with positive CDw75 expression (32.4%) was significantly lower than that of the
      patients without CDw75 expression (71.4%) (P<0.01). There was no significant
      correlation between the expression of CDw75 and the sex and age and histological
      type of patients (P>0.05). CONCLUSION: These findings suggest that the expression
      of CDw75 is a significant histopathological marker for more advanced stage of
      gastric carcinoma and indicates a poor prognosis for the patients.

PMID- 15162556
TI  - Got mold? Hospitals make progress in the fight against fungus.

PMID- 15162557
TI  - New wrinkles. Hospital bed makers talk about their product innovations.

PMID- 15162558
TI  - Stepping-->into security. Advice for facility managers overseeing the protection
      function.

PMID- 15162559
TI  - Seal of approval. ACCE rolls out a new certification for clinical engineers.

PMID- 15162560
TI  - On point. Reducing sharps injuries in the ES department.

PMID- 15162562
TI  - When management plays rough.

PMID- 15162563
TI  - Are you aware of your status with the federally mandated National Practitioner
      Data Bank?

PMID- 15162564
TI  - Research utilization: summarizing the research report.

PMID- 15162565
TI  - Fair and effective.

PMID- 15162566
TI  - Unreliable justice.

PMID- 15162568
TI  - Physicians health program message. Here to help.

PMID- 15162567
TI  - Policing the profession: are we catching "bad" doctors?

PMID- 15162569
TI  - Evidence-based medicine: ten hard facts.

PMID- 15162571
TI  - Do we currently have a malpractice crisis in Tennessee?

PMID- 15162570
TI  - Loss prevention case of the month. Critical documentation--the handoff: get the
      story straight.

PMID- 15162572
TI  - The other malpractice crisis: the link between malpractice liability and improved
      health.

PMID- 15162573
TI  - Latinos and their mental health.

PMID- 15162574
TI  - Chicago hospitals teaming-up to improve health education. Publisher, American
      Heart Association provide 'neutral' support.
AB  - In Chicago's southern section, known as Southland, the need for improved health
      status among the local population brought together marketing and business
      planning professionals from 11 healthcare entities that normally compete. Their
      group, named the Southland Health Alliance, came together to meet these urgent
      needs for better health education and lifestyle changes. With the visionary
      support of Midwest Suburban Publishing Co., they are collaborating on a year-long
      series of print advertisements addressing the problem faced by their community.

PMID- 15162575
TI  - Alegent's new Internet News Center. Reporters receive CD by way of introduction.
AB  - Alegent Health, Omaha, Neb., revised its News Center page on alegent.com, last
      September, with the idea of making information easy to find, easy to use, and
      available 24-7. The hospital then promoted the news center by means of an
      attractive direct mail piece containing an introductory CD.

PMID- 15162576
TI  - Television spots win national award. Part of OSF Saint Francis Medical Center's
      branding effort.
AB  - "Miracles in Medicine," a series of award-winning television spots, was produced
      for OSF Saint Francis Medical Center, Peoria, Ill., by The Roberts Group, Inc.,
      Waukesha, Wis. They are an integral part of a broader branding campaign, launched
      in May 2003, that includes newspaper, radio, and outdoor elements. The spots were
      deemed so successful, the branding effort was expanded to include Children's
      Hospital of Illinois.

PMID- 15162577
TI  - Princeton HealthCare System name reflects comprehensive services. New brand
      identity focuses on 'Redefining Care'.
AB  - The Medical Center at Princeton, Princeton, N.J., introduced its new name last
      June, both to its community and its internal stakeholders. It is now known as
      Princeton HealthCare System, a name chosen to reflect its growth and diversity.
      It's being branded as a unique institution that combines the sensitive, caring
      serice of a community hospital with the sophisticated care of a teaching
      hospital.

PMID- 15162578
TI  - Annual report features achievement. NorthEast Medical Center produces report for
      internal audience.
AB  - The 2002 Annual Report of the NorthEast Medical Center, is a summary of extensive
      quarterly reports issued by the Concord, N.C., hospital. Board members are the
      first recipients of the report, which is virtually used as a script at the annual
      meeting in January. Each of the hospital's 140 managers receive copies and
      encourage employees to read them as well.

PMID- 15162579
TI  - Baldrige Award cites two hospitals. Baptist, Saint Luke's hospitals honored for
      quality, performance.
AB  - Baptist Hospital Inc., Pensacola, Fla.; and Saint Luke's Hospital, Kansas City,
      Mo., have received the prestigious Malcolm Baldrige National Quality Award in the
      category of healthcare. Named for a former secretary of commerce, the award
      recognizes efficiency, effectiveness and excellence. The two hospitals are among
      only seven companies in the U.S. to be so recognized this year.

PMID- 15162580
TI  - King's Daughters Medical Center web site is an award winner.
AB  - King's Daughters Medical Center, Ashland, Ky., has an award-winning web site,
      www.kdmc.com, that attracts an average of 24,000 visits a month. Designed to be
      user-friendly and informative. The web site for the 366-bed regional referral
      center uses a newspaper-like style that makes it easily to update.

PMID- 15162581
TI  - Pediatrics in the panhandle. Part 2.

PMID- 15162582
TI  - Evaluation of a tuberculosis screening questionnaire for use in an Alaskan
      homeless population.
AB  - OBJECTIVE: To test the efficacy of a questionnaire for tuberculosis screening in
      an Alaskan homeless population. METHODS: Simultaneous PPD skin testing and
      questionnaire administration was performed at a free-meal facility to test the
      efficacy of a questionnaire for tuberculosis screening. "Positive" questionnaires
      were based on responses to symptom-based and risk-based questions. RESULTS:
      Demographic data was similar to pre-existing data for the Anchorage homeless
      population. Of the 64 participants, 3 were excluded and 47 (77%) returned for
      skin test readings. There were 8 (17%) positive, and 39 (83%) negative PPD tests,
      17 (36%) positive and 30 (64%) negative symptom-based questionnaires (Sensitivity
      25%, specificity 51%. PPV 13%, NPV 80%) and 28 (60%) positive, and 19 (40%)
      negative (n = 61) risk-based questionnaires (Sensitivity 63%, specificity 41%,
      PPV 18%, NVP 84%). CONCLUSION: The prevalence of TB warrants screening and
      treatment of the Anchorage, Alaska homeless population. However, this
      questionnaire was not useful for this population and therefore screening should
      be done using PPD skin tests.

PMID- 15162583
TI  - What ever happened to chlorosis? 1973.

PMID- 15162584
TI  - MEDLINE. Hotline to biomedical information. 1973.

PMID- 15162585
TI  - The changing face of medicine.

PMID- 15162586
TI  - Unstable angina.
AB  - Properly treated unstable angina and non-Q wave myocardial infarction have low
      hospital mortality, but untreated, mortality is high. Symptoms and labs usually
      suffice for diagnosis. Abnormal physical findings are rarely helpful and often
      absent. Careful surveillance and management substantially reduce long-term risks.

PMID- 15162587
TI  - Management of geriatric endocrine disorders.
AB  - Endocrine disorders in older adults are often detected on screening for unrelated
      medical conditions. Many disorders are precipitated during periods of stress.
      Despite a decline in certain hormonal levels endocrine functions of significance
      are well preserved in healthy older adults.

PMID- 15162588
TI  - Psychopharmaco-hazardology: major hazards of treating depression and anxiety.
AB  - Balancing the benefits and risks of prescribing psychotherapeutic drugs requires
      knowledge of both drug hazards as well as risk of untreated psychiatric illness.
      Screening for medical illnesses, substance abuse, suicidality, and unusual side
      effects is essential throughout treatment.

PMID- 15162589
TI  - Discussing life-sustaining treatments: an overview and communications guide for
      primary care physicians.
AB  - Physicians must be skilled communicators with patients, families, and
      multidisciplinary health care teams to meet ethical decision-making challenges
      arising in end-stage disease care. We offer practical suggestions for
      collaborative communication in the "perfect storm" of contemporary critical care
      settings.

PMID- 15162591
TI  - Severe health anxiety: why it persists and how to treat it.
AB  - Hypochondriasis (HA) involves the fear of serious illness despite appropriate
      reassurances. Because HA is associated with patients' personal suffering and
      clinical management problems, it is important for clinicians to be knowledgeable
      about current conceptual and treatment approaches to this problem.

PMID- 15162590
TI  - Psychosocial stress and cardiovascular disease: how to heal a broken heart.
AB  - Psychosocial stress induces adverse changes in autonomic tone accounting for
      substantial but modifiable cardiovascular risk. Various factors, including
      depression, social isolation, hostility and anxiety increase cardiovascular risk,
      whereas social support, altruism, faith and optimism reduce risk.

PMID- 15162592
TI  - Erectile dysfunction in the cardiac patient.
AB  - Erectile dysfunction (ED) is a common problem in men over 40-50 years of age.
      Risk factors include: diabetes, lipid abnormalities, smoking, hypertension,
      obesity, and lack of physical activity. Oral phosphodiesterase-5 inhibitors
      appear effective and safe in most cardiac patients.

PMID- 15162593
TI  - Acute bronchitis: state of the art diagnosis and therapy.
AB  - In managing acute bronchitis, pneumonia or an exacerbation of underlying chronic
      bronchitis should be excluded. Simple bronchitis is best treated symptomatically
      while an exacerbation of chronic bronchitis can be treated with antibiotics.
      Broad spectrum antibiotics are appropriate in selected patients.

PMID- 15162594
TI  - Can burden of obesity be factored into risk contracts?

PMID- 15162595
TI  - Clinical factors, not gatekeeping, dictate specialty referrals.

PMID- 15162596
TI  - Treat MS proactively in managed care setting.

PMID- 15162597
TI  - Benchmark your cap revenue against these IDS practices.

PMID- 15162598
TI  - Tracer methodology: how it can help you improve quality.
AB  - Tracer methodology follows patient through the entire continuum of care.
      Concurrent, rather than retrospective, approach is seen as a plus. Walk around
      creates opportunities to observe many different activities.

PMID- 15162599
TI  - QI program generates physician involvement.
AB  - Average HbA1c levels for participants were brought below the national average.
      Participation, voluntary for physicians at the beginning, now is mandatory.
      Education is a cornerstone, with several different vehicles of delivery.

PMID- 15162600
TI  - New tool adds structure, productivity to meetings.
AB  - Tool reinforces key mission and vision messages with staff personnel. Depending
      on meeting topic, one or all of the goals may be linked. Tool offers more
      balanced approach to decision making and problem solving.

PMID- 15162601
TI  - Quality, teamwork to be key issues for internists.
AB  - General internal medicine should remain true to its core values and competencies,
      according to a task force. The task force calls upon internists to be "quality
      accountable physicians." Many internists today have strong hospital connections.

PMID- 15162602
TI  - Staff education about environment starts day 1.
AB  - Part of Dartmouth-Hitchcock Medical Center's core mission is to be a good
      environmental steward. New employees are given a personal tour of waste
      management center. An environmental rep sits in on value and analysis committee
      meetings.

PMID- 15162603
TI  - Open access: whatever you may think, it works.

PMID- 15162604
TI  - EBM in AFP.

PMID- 15162605
TI  - Proceduralism would boost interest in the specialty.

PMID- 15162606
TI  - Physician couples and the Stark statute.

PMID- 15162607
TI  - Defending EBM.

PMID- 15162608
TI  - Simplifying the credentialing process.

PMID- 15162609
TI  - Implementing advanced access in a group practice network.
AB  - The leadership efforts in this complex process emphasize the importance of
      communication, education and buy-in to implement advanced access in a group
      practice network. These key components, along with timely feedback, staff support
      and necessary resources, are especially significant when the end point and the
      benefits are not immediately apparent to those directly affected by the change.
      Once these elements are in place, however, any practice has the ability to
      establish advanced access, increase its patient base and improve its economic
      performance.

PMID- 15162610
TI  - How to make the media your public health partner.

PMID- 15162611
TI  - A simple method for evaluating the clinical literature.

PMID- 15162612
TI  - Patient-physician partnering to improve chronic disease care.

PMID- 15162613
TI  - Blending work and family.

PMID- 15162614
TI  - A tale of two reports.

PMID- 15162615
TI  - Organizational ethics is "systems thinking".

PMID- 15162616
TI  - Don't forget hospital visitors.

PMID- 15162617
TI  - Who cares about ethics? Five ethicists and five executives discuss the importance
      of ethical guidance in Catholic health care today. Interview by Scott A.
      McConnaha.

PMID- 15162618
TI  - What's a Catholic to think? A genomics that promotes human flourishing can extend
      Jesus' mission.

PMID- 15162619
TI  - The "next generation" model. Ethics committee members are beginning to hold
      themselves responsible for measurable results.

PMID- 15162620
TI  - Stewardship and organizational ethics. How can hospitals and physicians balance
      scarce resources with their duty to serve the poor?

PMID- 15162621
TI  - An opportunity for civic leadership. In advocating health care reform, our
      ministry can also help reinvigorate U.S. democracy.

PMID- 15162622
TI  - Diversity in Catholic health care. Interview by Everard O. Rutledge.

PMID- 15162623
TI  - A shared vision of the future. Canada's counterpart to CHA convenes a national
      dialogue on a path for the Catholic health ministry.

PMID- 15162625
TI  - Operationalizing the standard of medical care: uses and limitations of
      epidemiology to guide expert testimony in medical negligence allegations.
AB  - In most U.S. jurisdictions, jurors are instructed that physicians must use "the
      skill and care ordinarily provided in similar circumstances." A failure to do so
      is called malpractice. However, how is a lay juror to know what ordinary medical
      care is? From physician experts testifying about their experience? Given that
      individual recollections of experience are likely to be skewed in the direction
      which, in retrospect, is preferred (the "Monday Morning Quarterback" phenomenon),
      and that the database upon which they are drawn is likely to be small (at least
      when compared with what might be available elsewhere), idiosyncratic
      generalizations of medical expert witnesses are almost certainly fraught with
      potential inaccuracies. Statistical descriptions of standard medical practices,
      published in peer-reviewed journals whenever possible, would provide a necessary
      buffer for jurors specifically, and the public more generally, against the
      inevitable possibility that an individual expert's experience is skewed, or
      recollection faulty.

PMID- 15162624
TI  - Being who we say we are. "Culture change" helps two long-term care centers align
      practice with their sponsors' values.

PMID- 15162626
TI  - Home healthcare quality.

PMID- 15162627
TI  - Using patient satisfaction data to improve home healthcare.
AB  - Patient satisfaction surveys are used extensively by home health agencies for a
      wide variety of purposes, but their utilization is often limited by a variety of
      practical and methodological problems. This article explores current and
      potential uses of satisfaction data and outlines steps that home health agencies
      may take to focus their use of these data to improve quality of care.

PMID- 15162629
TI  - Building a home healthcare workforce to meet the quality imperative.
AB  - The 1990s brought shifts in the organization and financing of healthcare services
      and changes to the nursing workforce as well. These changes were pronounced in
      home healthcare, where growth in service use between 1988 and 1996 was followed
      by sharp contractions in home healthcare users and visits after changes in
      Medicare reimbursement policy in 1997. This article examines how the nursing
      workforce has responded to these changes, explores the challenges posed by the
      nursing shortage, highlights the gap in knowledge of the staffing-outcomes
      relationship and its implications for quality, and offers recommendations on ways
      to improve care.

PMID- 15162628
TI  - Strengthening condition-specific evidence-based home healthcare practice.
AB  - The home health industry has lagged in adopting evidence-based care but is now
      well positioned to adopt such practices. However, few clinical practice
      guidelines have been developed for the home healthcare setting. This paper
      reviews the existing evidence base for prevalent home healthcare diagnoses and
      conditions and the progress made in applying those practices in home healthcare.
      Existing guidelines for congestive heart failure, diabetes, chronic obstructive
      pulmonary disease, falls, osteoarthritis, depression, and medication management
      could be modified for applicability to home healthcare. The evidence for a number
      of home healthcare practices is robust enough to argue for widespread
      dissemination and implementation.

PMID- 15162630
TI  - An informatics infrastructure for patient safety and evidence-based practice in
      home healthcare.
AB  - The informatics infrastructure for patient safety and evidence-based practice
      (EBP) in home healthcare comprises data acquisition methods, healthcare standards
      including standardized terminologies, data repositories and clinical event
      monitors, data-mining techniques, digital sources of evidence, and communication
      technologies. Although the components of an informatics infrastructure are
      available and applications that bring these components together to promote
      patient safety and enable EBP have demonstrated positive or promising results in
      the acute care setting, a number of challenges hinder implementation in home
      healthcare. Resolution of these challenges requires commitment and collaboration
      among key stakeholders.

PMID- 15162631
TI  - Penny Feldman on home healthcare quality and research. Interview by Susan V.
      White.
AB  - Penny Hollander Feldman, PhD, is Vice President for Research and Evaluation at
      the Visiting Nurse Service of New York (VNSNY) and Director of the Center for
      Home Care Policy and Research. Prior to joining VNSNY, Dr. Feldman served on the
      faculties of the Kennedy School of Government and the Department of Health Policy
      and Management at the Harvard School of Public Health. At the Center for Home
      Care Policy and Research, she directs projects focused on improving the quality,
      outcomes, and cost-effectiveness of home-based care, supporting informed
      policymaking by long-term care decision makers, and helping communities promote
      the health, well-being and independence of people with chronic illness or
      disability. The translation and implementation of research in both service and
      policy settings has been an issue of ongoing focus for Dr. Feldman. She also
      served as a member of the Institute of Medicine Committee on Improving the
      Quality of Long-Term Care, which issued its report in 2001.

PMID- 15162632
TI  - A case study of operational failure in home healthcare.
AB  - Examination of operational failures in home healthcare could yield important
      insights into improving patient safety. This article presents a case study of
      work system breakdowns observed in the home healthcare setting. The findings
      suggest that the biggest areas of opportunity are failures stemming from (a)
      insufficient support from home health agencies and (b) inadequate coordination
      with patients and their families. Factors that impede organizations from learning
      from employees' experiences with operational failures and steps that managers may
      take to overcome these hurdles are discussed.

PMID- 15162633
TI  - Data, information, and quality indicators for home healthcare: rapid
      implementation, what's next?
AB  - From 1999 to 2003, the home health industry in the United States moved from an
      environment with extremely diverse data collection protocols and little or no
      dissemination of quality-related information, to an environment in which
      uniformly collected clinical data are transformed into information and then into
      publicly available reports using federally mandated quality indicators. This
      speed to action has raised many questions about the adequacy of home healthcare
      data and their use as quality-monitoring tools. This article summarizes current
      evidence about the scientific and clinical adequacy of data currently used to
      measure home healthcare quality and discusses roles of a variety of policy
      stakeholders in implementing and refining data, information, and quality
      indicators that are now the cornerstones of federal home healthcare quality
      policy. The scientific adequacy of Outcome and Assessment Information Set data is
      acceptable but bears routine monitoring and review; efforts should be made to
      develop home healthcare quality indicators sensitive to nursing interventions and
      published clinical practice guidelines for specific medical conditions; and
      policy stakeholders should collaborate to maximize the utility of home healthcare
      quality reports now disseminated to consumers, providers, and insurers.

PMID- 15162634
TI  - Recurrent behavioral problems in children.

PMID- 15162635
TI  - A 3-year-old boy with previous illness, signs of meningitis, and seizures.

PMID- 15162637
TI  - Evaluating wickedness in children.
AB  - This article has reviewed one model for evaluating badly behaving or wicked
      children. Bad behavior is the final common pathway of a variety of biological,
      psychological, social, and cultural factors, and a proper evaluation requires
      knowledge of factors and clinical judgment as to the weight given to each factor.

PMID- 15162638
TI  - Psychopharmacologic treatment of aggression in children and adolescents.
AB  - Knowledge regarding psychopharmacology is increasingly based on clinical trials
      and rational algorithms. Medications are increasingly regarded as useful adjuncts
      in the treatment of maladaptive aggression, whether it appears as a target
      symptom or as a complication of a whole range of psychopathology. Properly
      integrated into a treatment package that uses psychotherapies and environmental
      manipulation, medications can provide relief from one of the most destructive
      forms of psychopathology. Still, more controlled clinical trials are needed,
      especially those comparing active interventions and those testing the synergistic
      and antagonistic effects of different treatment modalities.

PMID- 15162636
TI  - The psychophysiology of child misconduct.
AB  - Psychophysiological evidence supports the notion that serious and persistent
      childhood misconduct is symptomatic of an internal dysfunction that dynamically
      interacts with other psychological and social causes. Childhood misconduct is a
      complex phenomenon with multiple causes and no easy solutions. Rather than think
      our civilization is doomed, however, we should realize that the great majority of
      our children grow up to be sociable and law-abiding individuals. For the others,
      we are afforded optimism that this problem can be minimized as we gain a more
      complete understanding of the interplay among biological, psychological, and
      social risks, and through the consequent refinement of interventions.

PMID- 15162639
TI  - Neuropsychological characteristics of juvenile delinquency.
AB  - Knowledge of the neuropsychological characteristics related to JD and other
      behavioral disturbances in childhood is an important aspect of pediatric care.
      Referral of patients with developing behavioral problems for neuropsychological
      evaluation may assist pediatricians with identifying neuropsychological risk
      factors for JD, clarifying differential diagnostic questions, providing
      information for the nature of intervention efforts, and providing useful
      predictive tools for long-term planning and outcome. Thus, referrals for
      neuropsychological evaluation should not occur solely within the context of a
      patient with known central nervous system compromise. Neuropsychological results
      may be of benefit with disorders wherein the precise brain-behavior relationship
      is unclear, such as with JD. Once a child's neuropsychological characteristics
      are known and evaluated from a behavioral risk standpoint, pediatricians will
      have information that is pivotal to asserting recommendations for modifications
      to the home and school environments, as well as for direct intervention and
      treatment. The direction of future neuropsychological research includes the early
      identification of children and adolescents with potential behavioral disturbance.
      Accurate early differential diagnosis and knowledge of neuropsychological risk
      factors help to achieve this goal. Neuropsychological research and knowledge
      assist with understanding the complexities of interactions between environmental
      vulnerabilities and neuropsychological risk factors, and can provide useful
      predictive and preventative information for pediatricians.

PMID- 15162640
TI  - Who's idea is it?
AB  - You can avoid most but probably not all of the misunderstandings about "Who's
      idea is it?" The preventive strategies work. Fortunately, I was aware early in
      may career of the need to move rapidly from the idea to the proposal or written
      manuscript stages. In one instance, when I was attending a national meeting, I
      informally suggested a topic for a new nursing journal to the president of a
      publishing company. I heard his interest and automatically responded, "I will
      send you a written proposal next week." I sent a detailed, copyrighted proposal
      three days later, and it was accepted. As an author, reviewer, or editor, don't
      let your good ideas sit too long. By writing the details in a letter, outline, or
      proposal; including the copyright notice; and setting deadlines so the project
      moves to a finished manuscript, the idea will result in a successful publication.

PMID- 15162641
TI  - Spotting reference errors.
AB  - While authors are ultimately responsible to ensure that reference citations are
      correct, nurse editors and reviewers can use practical strategies to detect
      errors before publication. This author, an experienced reviewer, provides warning
      signs you can look for to uncover hidden citation errors as you review
      manuscripts.

PMID- 15162643
TI  - Patient-flow fixes ease ED crowding.

PMID- 15162642
TI  - Population of heavier patients demands planning, education.

PMID- 15162645
TI  - Safety in mobility for patients and staff.

PMID- 15162644
TI  - New standard aids in selecting barriers.

PMID- 15162646
TI  - Selecting equipment for obese patients.

PMID- 15162647
TI  - Internal bleeding: compelling tales of errors in health care.

PMID- 15162648
TI  - Hospitals, MDs compete for core business.

PMID- 15162649
TI  - New guide to safer sharps for the OR.

PMID- 15162650
TI  - Is there a patient weight limit for ASCs?

PMID- 15162651
TI  - Getting ready for JCAHO's tracer method.

PMID- 15162652
TI  - The European Network of Health Care Chaplaincy--a growing hope.

PMID- 15162653
TI  - What language shall I borrow? The poetry of Rainer Maria Rilke and the care of
      souls.
AB  - This article suggests that the reality of the world is socially constructed
      through the words and narratives chosen and used. These social constructions may
      be from science and technology, business and economics, or poetry and metaphors,
      and as such each shapes a different world. The work of the poet Rainer Maria
      Rilke is used to illustrate how the power of words and images shape and form the
      world. The implications of the use of language for the care of souls are
      discussed.

PMID- 15162654
TI  - The communion of saints as a paradigm for pastoral counseling: a revised look at
      an ancient symbol.
AB  - The Christian symbol of the Communion of Saints has stood for centuries as a call
      to celebrate relationships. From the ancient doctrine of calling out those
      honored among the faithful for their holiness, the symbol evolved into a more
      formal ecclesial process involving procedures and miraculous proof. Reaching back
      to the early roots, the author draws on theologian Elizabeth Johnson's
      revisioning of saints as "friends and prophets" to explore a paradigm for the
      pastoral counselor. Such pastoral characteristics as presence, transforming
      vision, and creative hope are explored for the richness of growth within the
      counseling relationship for all who enter into it.

PMID- 15162655
TI  - How are health care chaplains helpful to bereaved family members? Telephone
      survey results.
AB  - After conducting telephone interviews with 130 next-of-kin whose loved one died,
      the authors report whether and how chaplains were helpful to these family
      members. Analysis of their responses indicated that chaplains were helpful in
      five ways. They provided comfort and support; they helped family members with
      details before, during, and after death; they acted as surrogate family members
      until other loved ones arrived; their availability provided a safety net even if
      contact was limited; and they functioned as a spiritual figure who provided the
      transition of the patient from earth to heaven. Family members rated the
      helpfulness of chaplains as midway between very good and excellent.

PMID- 15162656
TI  - Pastoral care following pregnancy loss: the role of ritual.
AB  - The authors propose a model for different ways in which clergy of diverse
      denominations ritualize pregnancy loss through excerpts from 23 interviews with
      Chicago-area religious leaders. These clergy either do not ritualize pregnancy
      loss at all, adapt existing rituals, or create new ones.

PMID- 15162657
TI  - Promoting patient safety: implications for pastoral care.
AB  - This article provides an overview of current issues in patient safety, the
      subject of recently-implemented JCAHO standards, with attention to issues of
      special interest to pastoral care professionals and Clinical Pastoral Education
      (CPE) students. Case studies of patient safety initiatives in two health care
      systems are used to illustrate the relationship between institutional core values
      and the just treatment of injured patients and their families, and to suggest
      opportunities for chaplains to contribute to patient safety efforts in their
      institutions. A list of suggested readings and online resources is included.

PMID- 15162658
TI  - Marital and Relationship Ministry (MRM) as a tenant of pastoral care.
AB  - Although marital and relationship support programs are available for couples, few
      churches offer comprehensive marital and relationship ministry (MRM). This
      research examined MRM topics and formats desired by congregants and advocated
      adoption by clergy of MRM as a tenant of pastoral care. Eight faith communities
      in a Midwestern city were non-randomly selected for ethnic and denominational
      diversity. Overall analyses indicated congregants desired specific areas of
      marital and relationship ministry that included communication, family, and
      enrichment topics.

PMID- 15162659
TI  - On evil, sin, and suffering: toward a hermeneutic of their relation.
AB  - Historically, evil, illness, and suffering have been interpreted in religious
      communities as having the imprint of Providence. Many traditions continue to hold
      to this world view. But increasingly with the burgeoning of technology and the
      advent of palliative care, more and more religious persons struggle to maintain
      this belief. Suffering as such no longer holds the kind of "purifying effect"
      that it once was thought to have. Indeed, particularly with our capacity to
      mitigate physical suffering with drugs such as methadone and morphine, the belief
      that all suffering has a purpose seems to have lost its appeal. This article
      examines and challenges the underlying assumptions that continue to undergird
      religious communities--particularly sacramental ones--that evil, illness, and
      suffering are linked to notions such as sin and healing.

PMID- 15162660
TI  - Healing the wounds and the wounds of healing: a journey of the spirit.
AB  - This article is a reflective narrative about the death of a parent told from the
      perspective of her daughter. It is an experience-based account. This shared
      journey of mother and child links the familiar realm of the conscious and known
      self to a realm that is not known in the same way and is not merely the self. It
      is as if one end is in the midst of life's struggles and crises and the other in
      another realm; yet the whole works together as a single force. In this way the
      idea is introduced that the very challenges and trauma of life can be a wound
      that is a healing of wounds, in so far as it prompts recognition of the realm
      that is out of sight, though the wound certainly is real enough.

PMID- 15162661
TI  - Virtual visiting seminar replaces verbatim seminar in Clinical Pastoral Education
      (CPE).
AB  - The article addresses the question of the value of the virtual visiting seminar
      compared to the verbatim seminar in a Clinical Pastoral Education (CPE) Unit. A
      Virtual Visit occurs when a volunteer allows a CPE student to engage them in a
      pastoral visit with the expressed purpose of providing feedback to the student.
      The effectiveness of the virtual visiting seminar was monitored by a Site Review
      Team, two independent expert witnesses, by students who have experienced both
      learning tools, and the Education Sub Committee of the Pastoral Care Advisory
      Committee. The results point to advantages of the virtual visiting seminar over
      the verbatim seminar.

PMID- 15162662
TI  - PAUSE for assessment: a multi-level long-term care assessment tool.
AB  - The author of this article noes that as health care improves, paradoxically, long
      term care residents become "older and sicker." In response, many facilities now
      offer a wide range of levels of residential care, from independent living to
      Hospice care--and all under the same roof. Chaplains in such facilities can play
      a key part in identifying changes in individual residents' needs over time.
      Toward this end, the author introduces PAUSE--a one-page questionnaire designed
      to be completed by the chaplain after a visit with a resident. The items reflect
      the chaplain's impressions of several key aspects of the resident's well-being
      from a single interaction. The questionnaire serves several purposes: it
      documents the fact of a visit; it allows comparison of impressions at different
      times and by different visitors; and it quickly highlights "red flag" areas of
      possible concern for interdisciplinary referral, pastoral follow-up, or possible
      change in level of care. It might also function as a teaching tool for student
      chaplains.

PMID- 15162663
TI  - When God stops talking.

PMID- 15162664
TI  - Research on religion and health: a second response.

PMID- 15162665
TI  - Factors affecting healthcare chaplaincy and the provision of pastoral care in the
      United States.

PMID- 15162666
TI  - USC School of Medicine--MUSC College of Medicine Collaborations: current status
      and future directions.

PMID- 15162668
TI  - Recognition and implications of the metabolic syndrome.

PMID- 15162667
TI  - Patients' perceptions of non-physician providers in primary care.
AB  - Patients in this study were most comfortable receiving primary care services from
      physicians trained in primary care specialties. There was, however, a racial
      difference in the comfort level of primary care being provided by non-physician
      providers with minority populations being more comfortable with non-physician
      providers. More research is needed to understand the role that non-physician
      providers play in the primary care delivery system in the United States.

PMID- 15162669
TI  - Brucellosis in two hunt club members in South Carolina.
AB  - We report two cases of brucellosis in members of a hunt club, both of whom had
      killed and dressed wild boars. Serologic studies usually suffice for screening
      patients with suspected or possible brucellosis; however, and as illustrated by
      our index case, one should ask the laboratory to dilute serum out beyond the
      customary 1:160 titer if results are negative yet the clinical suspicion high.
      Hunters should be advised to wear gloves prior to dressing wild mammals.

PMID- 15162671
TI  - Impress Joint Commission and public with dramatic core measure results.

PMID- 15162670
TI  - Advancing medical professionalism. II. One size does not fit all.

PMID- 15162672
TI  - Try these foolproof tips to be ready for JCAHO.

PMID- 15162673
TI  - Project aids rural hospitals in drug error reporting.

PMID- 15162674
TI  - Report, new measures link nursing care to safety.

PMID- 15162675
TI  - Make these changes to improve safety.

PMID- 15162676
TI  - Use Baldrige criteria to advance excellence.

PMID- 15162677
TI  - Perspectives. Trade pacts won't solve drug-price woes.

PMID- 15162678
TI  - New taxa, new records and redefined concepts in the Elaphoglossum sect.
      Elaphoglossum subsec. Pachyglossa (Lomariopsidaceae) from Mexico and Central
      America.
AB  - Twelve new species are described in the taxonomically difficult Elaphoglossum
      (sect. Elaphoglossum): Elaphoglossum angustifrons A. Rojas, E. delgadilloanum A.
      Rojas, E. ellipticifolium A. Rojas, E. incognitum A. Rojas, E. mesoamericanum A.
      Rojas, E. nicaraguese A. Rojas, E. polypodium A. Rojas, E. tejeroanum A. Rojas,
      E. reptans A. Rojas, E. terrestre A. Rojas, E. variabile A. Rojas and E. zavale
      A. Rojas. Also, E. latifolium (Sw.) J. Sm., E. sartorii (Liebm.) Mickel and E.
      viride (E. Fourn.) C. Chr. are amended, E. andicola (Fee) T. Moore and E.
      sporadolepis (Kunze ex Kuhn) T. Moore are reported.

PMID- 15162679
TI  - Notes on Elaphoglossum (Lomariopsidaceae) section Polytrichia subsection Hybrida
      in Mexico and Central America.
AB  - In Elaphoglossum sect. Polytrichia subsect. Hybrida six new species are
      described: E. angustioblongum A. Rojas, E. baquianorum A. Rojas, E. cotoi A.
      Rojas, E. jinoteganum A. Rojas, E. neeanum A. Rojas and E. silencioanum A. Rojas.
      New combination is made for Elaphoglossum mexicanum (E. Fourn.) A. Rojas. Two
      species are reported: E. barbatum (H. Karst.) Hieron. and E. scolopendrifolium
      (Raddi) J. Sm. Two species are redefined: E. erinaceum (Fee) T. Moore and E.
      tambillense (Hook.) T. Moore. E. pallidum (Baker ex Jenman) C. Chr. is eliminated
      for Mexico and Central America. Of the new species only E. neeanum is present
      outside of the region. A key is given to those species in Mexico and Central
      America.

PMID- 15162680
TI  - [Prothallia in nine species of Callipteris and its comparison with other genera
      of the Woodsiaceae family].
AB  - The development of the prothallia in nine species of Callipteris Bory
      (Woodsiaceae), four species of Diplazium, the genus from which Callipteris has
      been segregated, and one species of Dryoathyrium are studied in this paper. The
      data obtained are compared with the development of the prothallia of several
      other genera of Woodsiaceae. The main difference between Callipteris and the
      other genera of Woodsiaceae was that the antheridia dehiscence of Callipteris,
      occurs by an opercular cell and whereas some of Diplazium and other Woodsiaceae
      antheridia dehiscence occurs by a lateral or apical pore. The presence of
      antheridiogens is suspected on the basis of small ameristic male gametophytes in
      the cultures. Spore germination in Callipteris is Vittaria-type, prothallial
      development corresponds to Adiantum-type.

PMID- 15162681
TI  - Invasion by Ligustrum lucidum (Oleaceae) in NW Argentina: early stage
      characteristics in different habitat types.
AB  - Currently biological invasions are considered one of the world's most serious
      conservation problems. Ligustrum lucidum is the most abundant exotic tree in
      secondary forest patches of montane forests of NW Argentina. We studied the
      determinants of success of the early stages of its life cycle in distinct habitat
      types, with the hope of identifying vulnerabilities that could be exploited to
      control the invasion. Seed arrival, germination, seedling recruitment and
      survival, and sapling growth were studied in edges, gaps and forest interior.
      Seed arrival was also assessed under perches and in open fields. Germination was
      studied in forest and grassland patches. L. lucidum seedling survival and sapling
      growth were compared with the most abundant native species survival and growth.
      Seed arrival was strongly seasonal with a peak in mid-August. Seed rain did not
      differ significantly among habitat types, however there was a tendency for edges
      to receive more seeds when only dispersed seeds were considered. Perches strongly
      enhanced seed arrival; more than 40 times the number of seeds were dispersed
      beneath citrus plants (i.e. perches) than found in paired open areas. In the
      forest, seeds in gaps and edges had higher germination rates, but there was no
      difference in seedling survival. Fruits under closed canopy exhibited the lowest
      germination. Germination and survival were low in open areas. Neither seedling
      recruitment nor sapling growth differed between gaps and forest interior. L.
      lucidum saplings grew significantly more than saplings of the most common native
      species, and also showed higher seedling survival. L. lucidum is a prolific fruit
      producer, is capable of germinating and surviving in a broad range of forest
      environments, it is relatively shade tolerant and has higher survival and faster
      growth rate in comparison to the most common native species. All these
      characteristics highlight its potency as a successful invader, and point to few
      vulnerabilities that could be targets of control measures.

PMID- 15162682
TI  - Effects of floral display and plant abundance on fruit production of Ryncholaelia
      glauca (Orchidaceae).
AB  - Flowering plant density can increase number of visits and fruit set in multi
      flowering plants, however this aspect has not been studied on few flower species.
      We studied the effects of individual floral display and plant density on the
      fruit production of the epiphytic, moth-pollinated orchid, Ryncholaelia glauca,
      in an oak forest of Chavarrillo, Veracruz, Mexico. Species is non-autogamous, and
      produced one flower per flowering shoot each flowering season. We hypothesized
      that orchids with more flowering shoots and those on trees with clumps of
      conspecific should develop more fruits than isolated ones. R. glauca population
      flowers synchronouly, and individual flowers last up to 18 days, with flowers
      closing rapidly after pollination. Individuals produced few flowers per year,
      although some plants developed flowers in both seasons and fewer of them
      developed fruits both years. There was no relationship between flower number per
      orchid, or per host tree, with the number of fruits developed per plant. Host
      trees with flowering and fruiting orchids were randomly dispersed and the pattern
      of distribution of flowering and fruiting plants was not related. Apparently,
      pollinators visit the flowers randomly, with no evidence of density dependence.
      The fruit set of R. glauca was as low as fruit set of multi-flowered orchids moth
      pollinated, suggesting that fruit set on moth pollinated orchids could be
      independent of the number of flowers displayed.

PMID- 15162683
TI  - Calvatia sporocristata sp. nov. (Gasteromycetes) from Costa Rica.
AB  - Calvatia sporocristata, Gasteromycetes, is described and illustrated as a new
      species. Its taxonomic characters are discussed and compared with other closely
      related species of the genus. Few studies have been carried out on tropical
      Gasteromycetes. The new species here proposed has, as the main features:
      exoperidium corky, smooth, one-layered, pseudoparenchymatous; endoperidium thin,
      papyraceous, dextrinoid; subgleba cellular; capillitium septate, dissociated at
      the septal site, lycoperdon type, without pores, elastic and spores amigdaloid, 4
      6 (-7) x 2.5-4.5 microns with spines aligned, forming crests, 0.8 micron high.

PMID- 15162685
TI  - On the phytoplankton of Awba reservoir, Ibadan, Nigeria.
AB  - The physico-chemical characteristics and phytoplankton of Awba reservoir in the
      University of Ibadan, Nigeria, were monitored to determine the impact of
      eutrophication on phytoplankton composition. The principal component analysis
      identified three major components influencing the physicochemistry of the water,
      namely trace metals, dissolved oxygen and ionic composition. Comparative analysis
      with a previous study showed a phenomenal increase in zinc, copper and iron
      levels over a 10-year period. Furthermore, the ferruginous nature of the soil
      contributed to the high levels of iron which exceeded the World Health
      Organization Standards for drinking water quality. The most abundant
      phytoplankton species was Microcystis aeruginosa which has been implicated in
      toxic blooms in freshwaters. The conditions favouring cyanophyte blooms and their
      implications are discussed.

PMID- 15162684
TI  - Heterotrophic microbial activity and organic matter degradation in coastal
      lagoons of Colombia.
AB  - In this study we measured the community respiration and the bacterial respiration
      as part of the overall degradation process of organic material. Additionally, the
      turnover rates of the pools of dissolved free glucose and acetate as
      representatives of the fraction of easily degradable low molecular organic
      solutes were determined. The study was performed in several coastal lagoons of
      the "Outer Delta of the Rio Magdalena" in northern Colombia. The lagoons can be
      separated into two groups: The first group contains highly productive brackish
      lagoons with chl a concentrations ranging from 62-130 micrograms/l. The second
      group consists of less productive freshwater lagoons with chl a between 5.5-19
      micrograms/l. Turnover rates of glucose and acetate were very fast in the highly
      productive lagoons resulting in turnover times of less than 20 min for both
      compounds. In the less productive systems the cycling of glucose and acetate was
      much slower. Here the mean values of the turnover times were 2 hr for glucose and
      1.5 hr for acetate. The rates of bacterial DNA-formation measured as thymidine
      incorporation differed significantly between both groups of lagoons, being very
      high (1.86-2.76 nmol/l/hr) in the highly productive and relatively low (0.073
      0.55 nmol/l/hr) in the less productive group. Water column community respiration
      ranged between 122 and 16 micrograms C/l/hr with means of 88 micrograms C/l/hr in
      the highly and 19 micrograms C/l/hr in the less productive group. In the first
      group the mean values of the bacterial contribution to community respiration
      amounted to 37% and in the second group to 18%. The bacterial respiration was
      determined in an indirect way via bacterial biomass production and assuming a
      growth efficiency of 50%. It is discussed whether this relatively high growth
      efficiency allows reasonable results in both groups of lagoons.

PMID- 15162686
TI  - Basic limnology of fifty-one lakes in Costa Rica.
AB  - We visited 51 lakes in Costa Rica as part of a broad-based survey to document
      their physical and chemical characteristics and how these relate to the mode of
      formation and geographical distribution of the lakes. The four oxbow lakes were
      low in elevation and tended to be turbid, high in conductivity and CO2, but low
      in dissolved O2; one of these, L. Gandoca, had a hypolimnion essentially composed
      of sea water. These were similar to the four wetland lakes, but the latter
      instead had low conductivities and pH, and turbidity was often due to tannins
      rather than suspended sediments. The thirteen artificial lakes formed a very
      heterogenous group, whose features varied depending on local factors. The
      thirteen lakes dammed by landslides, lava flows, or lahars occurred in areas with
      steep slopes, and were more likely to be stratified than most other types of
      lakes. The eight lakes that occupy volcanic craters tended to be deep,
      stratified, clear, and cool; two of these, L. Hule and L. Rio Cuarto, appeared to
      be oligomictic (tending toward meromictic). The nine glacial lakes, all located
      above 3440 m elevation near Cerro Chirripo, were clear, cold, dilute, and are
      probably polymictic. Cluster analysis resulted in three significant groups of
      lakes. Cluster 1 included four calcium-rich lakes (average 48 mg l-1), Cluster 2
      included fourteen lakes with more Si than Ca+2 and higher Cl- than the other
      clusters, and Cluster 3 included the remaining thirty-three lakes that were
      generally less concentrated. Each cluster included lakes of various origins
      located in different geographical regions; these data indicate that, apart from
      the high-altitude glacial lakes and lakes in the Miravalles area, similarity in
      lake chemistry is independent of lake distribution.

PMID- 15162687
TI  - Shallow-water Campanulariidae (Hydrozoa, Leptothecatae) from northern Bahia,
      Brazil.
AB  - This study provides the first semi-quantititative account of the benthic
      campanulariid hydroids from Northern Bahia (Brazil), down to a depth of 60 m,
      based largely on collections obtained since 1992. Colonies were collected from
      six habitats along the coast of Salvador City, Todos os Santos Bay, Itaparica
      Island and at the northernmost part of the coast of the State of Bahia. From the
      982 colonies examined, nine species were recorded: Campanularia hincksii, Clytia
      gracilis, C. hemisphaerica, C. hummelincki, C. linearis, C. macrotheca, C.
      noliformis, Obelia bidentata and O. dichotoma. Following a defined abundance
      scale, Clytia gracilis and C. noliformis were the most abundant species, whereas
      Campanularia hincksii and Clytia hummelincki were rare. Cluster analysis of
      relative abundance data revealed sandy shores had a markedly different hydroid
      community from other habitats. A simplified identification key, redescriptions,
      illustrations and data on nematocyst compliment are provided for each species.
      Campanularia hincksii, Clytia macrotheca and C. noliformis are reported from
      Brazil for the first time.

PMID- 15162689
TI  - A new estuarine species, Nereis garwoodi (Polychaeta: Nereididae), from Bahia
      Chetumal, Mexican Caribbean coast.
AB  - Nereis garwoodi n. sp. is described on the basis of eight syntype specimens (six
      atokous and two heteronereis) collected in Bahia Chetumal, Mexican Caribbean
      coast, and the variability in the paragnath numbers in the pharynx is established
      using 180 specimens; paragnath numbers are I:10(SD = 1.9); II:30 (SD = 2.6);
      III:41 (SD = 5.2); IV:29 (SD = 3.5), V:1, VI:4, VII-VIII: > 30. Its eyes are big
      and its longest tentacular cirri reaches setiger 11. A revised key to species of
      Nereis recorded from the Grand Caribbean Sea is included.

PMID- 15162688
TI  - Asexual reproduction and molecular systematics of the sea anemone Anthopleura
      krebsi (Actiniaria: Actiniidae).
AB  - In this paper we use allozyme analyses to demonstrate that individuals in
      Anthopleura krebsi aggregates are monoclonal. Additionally, sympatric samples of
      the red and the green colour-morphs of A. krebsi from Pernambuco, Brazil were
      genetically compared and no significant differences were observed between them
      (gene identity = 0.992), indicating that they do not belong to different
      biological species. All individuals within aggregates of the green colour-morph
      were found to be identical over the five polymorphic loci analysed. Such results
      would be extremely unlikely (P < 10(-11)) if the individuals analysed had been
      generated through sexual reproduction, thus confirming the presence of asexual
      reproduction in this species.

PMID- 15162690
TI  - Factors affecting growth of the spiny lobsters Panulirus gracilis and Panulirus
      inflatus (Decapoda: Palinuridae) in Guerrero, Mexico.
AB  - The effects of sex, injuries, season and site on the growth of the spiny lobsters
      Panulirus gracilis, and P. inflatus, were studied through mark-recapture
      techniques in two sites with different ecological characteristics on the coast of
      Guerrero, Mexico. Panulirus gracilis occurred in both sites, whereas P. inflatus
      occurred only in one site. All recaptured individuals were adults. Both species
      had similar intermolt periods, but P. gracilis had significantly higher growth
      rates (mm carapace length week-1) than P. inflatus as a result of a larger molt
      increment. Growth rates of males were higher than those of females in both
      species owing to larger molt increments and shorter intermolt periods in males.
      Injuries had no effect on growth rates in either species. Individuals of P.
      gracilis grew faster in site 1 than in site 2. Therefore, the effect of season on
      growth of P. gracilis was analyzed separately in each site. In site 2, growth
      rates of P. gracilis were similar in summer and in winter, whereas in site 1 both
      species had higher growth rates in winter than in summer. This could be due to
      spatial differences in processes related to changes in population density and
      food resources, which were documented in previous works. The overall results show
      that P. gracilis grows faster than P. inflatus, and that growth rates of both
      species are highly variable and are affected by environmental factors such as
      site and season, which should be taken into account when attempting to produce
      population growth curves for each species.

PMID- 15162691
TI  - Littoral decapods of Socorro Island, Revillagigedo Archipelago, Mexico.
AB  - Decapod community inhabiting the rocky littoral of eight bays from Socorro
      island, Revillagigedo Archipelago, was studied during March 1992. Samples were
      collected from one-square meter plots placed following transects drawn
      perpendicularly to the shoreline along the intertidal zone. Species richness and
      abundance were determined in each bay, as well as the similarity between bays
      using Morisita's index. Organisms collected belong to six families, 20 genera and
      26 species of the Brachyura and Anomura infraorders. Xanthidae was the family
      with the highest number of species, and the highest species richness was recorded
      at the V. Lozano bay. Pachygrapsus transversus, Xanthodius cooksoni and Calcinus
      explorator were the most abundant species in nearly all localities. Dendrogram
      obtained define two groups of bays at a similarity level above 0.67, given the
      similarity in the crab's species richness and their abundance between bays in the
      island.

PMID- 15162692
TI  - [Diversity and distribution of crustaceans and echinoderms and their relation
      with sedimentation levels in coral reefs].
AB  - Seven reef formations were studied in South Caicos, Turks & Caicos, to determine
      the species richness, patterns of diversity and patterns of distribution of
      crustaceans and echinoderms, and to evaluate the relationship between these
      parameters and the degree of sedimentation of the different sites. The reefs
      showed a gradient from a high sedimentation level, almost totally covered by
      algae, to places with no sediment particles deposited over the corals. Sites were
      classified as with high, low or null sedimentation, and species richness,
      abundance, diversity, spatial distribution of species and similarity among sites
      were estimated. No unique pattern was found: for crustaceans as well as for
      echinoderms, the site with the highest diversity value and high equitability,
      presumably associated to the environmental heterogeneity of this reef formation,
      showed null sedimentation and an uniform and random pattern of distribution,
      crustaceans and echinoderms respectively. The two sites with the lowest diversity
      for both animal groups, although with different sedimentation levels, showed the
      lowest equitability value and were the only sites with an aggregated pattern of
      distribution. The next sites in diversity for crustaceans were those with high
      sedimentation, probably because most species present inhabit empty conchs, in the
      sediment, or among seagrass. For the echinoderms, on the contrary, the
      intermediate sites in diversity had low sedimentation; the habitat requirements
      for these species (inside sponges, over the corals or among rocks) may have
      determined this result. The sites with lowest diversity had high sedimentation
      levels. In these, crustaceans showed the lowest equitability values and an
      aggregated spatial distribution, while the community of echinoderms was dominated
      by one single species. Although only general descriptions can be elucidated with
      the present results, knowledge about the basic population characteristics and
      natural history of these reef communities, combined with that of the
      perturbations related to human activities, provides useful base information for
      appropriate planning for the restoration and conservation of this ecosystem.

PMID- 15162693
TI  - A new species of Ulmeritoides from Brazil (Ephemeroptera: Leptophlebiidae).
AB  - The leptophlebiid mayfly genus Ulmeritoides is composed of nine species, three of
      which have been recorded in Brazil: U. patagianus, U. uruguayensis, and U.
      misionensis. In the present paper, a new species of this genus, Ulmeritoides oepa
      sp.nov., is described and illustrated based on fifteen larvae collected in
      Uraricoera River, state of Roraima, northern Brazil. The species was compared to
      U. misionensis, U. tifferae, and U. guanacaste, the other species of Ulmeritoides
      known from the larval stage. U. opea sp.nov. can be distinguished from these
      species by the following combination of characteristics: 1) medial denticle on
      anteromedian emargination of labrum much larger than others; 2) anterior tibiae
      slightly stained black toward the apex; 3) medial femora with few dorsal spines,
      similar to short thick needles; 4) hind femora with numerous dorsal spines,
      similar to short thick needles; 5) medial femora with no medial black markings,
      apical brown markings. The new species seems to be more closely related to U.
      misionensis, another species in which the anteromedian emargination of the labrum
      has a median denticle much larger than the others. The studied specimens were
      deposited in the Invertebrates Collection of the Amazonian Research National
      Institute, Manaus, state of Amazonas, Brazil, and in the Entomological Collection
      of the Department of Zoology, Federal University of Rio Janeiro, Rio de Janeiro,
      state of Rio de Janeiro, Brazil.

PMID- 15162694
TI  - Caterpillars of Eumaeus childrenae (Lepidoptera: Lycaenidae) feeding on two
      species of cycads (Zamiaceae) in the Huasteca region, Mexico.
AB  - There are few genera of butterflies that feed on cycads. Among them the genus
      Eumaeus (Lycaenidae) presents aposematic coloration in all its life stages. In
      this work we report for the first time the herbivory of young leaflets of
      Ceratozamia mexicana and Zamia fischeri (Zamiaceae) by caterpillars of E.
      childrenae in their natural habitat in the Huasteca region, Mexico.

PMID- 15162695
TI  - Relationships between necrotic cactus availability and population size in a
      cactophilic Drosophila (Diptera, Drosophilidae) located on a sandstone table hill
      in Brazil.
AB  - Drosophila gouveai is a cactophilic species endemic to South America. In
      southeast Brazil it is found on summits of isolated hills, which apparently are
      current refugia resulting from climatic changes during the Quaternary Period. It
      breeds only in necrotic cactus cladodes of Pilosocereus machrisii. Temporal
      differences in necrotic cactus availability could have a great impact upon D.
      gouveai population size, and could thus influence its evolutionary history. We
      analyzed the relationship between necrotic cactus availability and population
      size of D. gouveai. The fluctuation in the population size, variation in necrotic
      cactus availability and exploitation of this resource by larvae were surveyed
      bimonthly for one year on a sandstone table hill in central-south Brazil.
      Temporal necrotic cactus availability did not vary significantly, though in June
      there was a moderate decrease Larval populations were highest in October and
      December. The D. gouveai population size was highest in February and remained
      relatively stable the rest of the year. The observed fluctuation in population
      size was not a function of temporal necrotic cactus availability in quantitative
      terms.

PMID- 15162696
TI  - [Association of the abundance and vertical distribution of tuna and beakfish in
      the southeast of the Caribbean sea].
AB  - The longline hooks suspension depth was estimated using the Mechanic Imitation of
      Flexible Systems method. The vertical distribution of tunas and billfish was
      determined by the relative abundance index, obtained from the catch by 11 to 25 m
      -long longline vessels, -based at Cumana, Venezuela, South-eastern Caribbean Sea
      in depths of 65 to 142 m. The CPUE was evaluated per species, according to depth.
      High values were found for most of the captured species in the layer from 105 to
      125 m. Yellowfin tuna (Thunnus albacares) showed the highest yield (3.37 fish/100
      hooks) and blue marlin (Makaira nigricans) the lowest (0.04 fish/100 hooks).
      However, the statistical comparison did not allow to reject the hypothesis of
      lack of depth efect (Kruskal-Wallis p > .05), and demonstrated a homogeneous
      distribution of yellowfin tuna (Thunnus albacares), albacore (Thunnus alalunga),
      bigeye tuna (Thunnus obesus), sailfish (Istiophorus albicans), white marlin
      (Tetrapturus albidus) and blue marlin (Makaira nigricans) in the water column.
      The conclusion is that fish concentration in the Southern border of the Caribbean
      Sea is possibly due to several hydroclimatic factors--which affect tuna and
      billfish catching--such as water temperature and dissolved oxygen concentration
      which limit the distribution according to depth.

PMID- 15162697
TI  - Reproductive aspects of Oreochromis niloticus (Perciformes: Cichlidae) at
      Coatetelco Lake, Morelos, Mexico.
AB  - Sex ratio, size at maturity, maturity stages, fecundity and egg diameter of
      Oreochromis niloticus from Coatetelco Lake, Morelos State, Mexico, were studied
      from January to December 1993. Sex ratio (male:female) was approximately 1:1.02.
      Length at maturity was 117 mm (males) and 120 mm (females). The fecundity ranged
      between 104 and 709 eggs, with egg diameter from 1,000 to 3,000 microns. The
      gonadosomatic and hepatosomatic index indicate that the species breeds during
      summer and winter.

PMID- 15162699
TI  - Sexual dimorphism in Ramphastos toco and Ramphastos dicolorus (Piciformes, Aves).
AB  - Phenotypic sexual dimorphism seems to be rare in the Ramphastidae family, except
      in Pteroglossus viridis and in the genus Selenidera. Many breeders of wild birds
      believe that specimens of Ramphastos toco can be sexed using bill
      characteristics. In this study, various discriminant phenotypic variables were
      analyzed in birds which were sexed cytogenetically. Fifty-one specimens of R.
      toco and 20 R. dicolorus were studied. The statistically significant parameters
      which served to distinguish the sex in these species were the length of the
      culmen and tomium, length of the lower corneous beak and the cloaca. Using these
      parameters, captive bird breeders can determine sex of R. toco specimens by
      phenotypic analysis and form breeding couples more quickly.

PMID- 15162698
TI  - [Demography and nesting ecology of green iguana, Iguana iguana (Squamata:
      Iguanidae), in 2 exploited populations in Depresion Momposina, Colombia].
AB  - We studied the demography and nesting ecology of two populations of Iguana iguana
      that face heavy exploitation and habitat modification in the Momposina
      Depression, Colombia. Lineal transect data was analyzed using the Fourier model
      to provide estimates of social group densities, which was found to differ both
      within and among populations (1.05-6.0 groups/ha). Mean group size and overall
      iguana density estimates varied between populations as well (1.5-13.7
      iguanas/ha). The density estimates were far lower than those reported from more
      protected areas in Panama and Venezuela. Iguana densities were consistently
      higher in sites located along rivers (2.5 iguanas/group) than in sites along the
      margin of marshes, probably due to vegetational differences (1.5 iguanas/group).
      There was no correlation between density estimates and estimates of relative
      abundance (number of iguanas seen/hour/person) due to differing detectabilities
      of iguana groups among sites. The adult sex ratio (1:2.5 males:females) agreed
      well with other reports in the literature based upon observation of adult social
      groups, and probably results from the polygynous mating system in this species
      rather than a real demographic skew. Nesting in this population occurs from the
      end of January through March and hatching occurs between April and May. We
      monitored 34 nests, which suffered little vertebrate predation, perhaps due to
      the lack of a complete vertebrate fauna in this densely inhabited area, but nests
      suffered from inundation, cattle trampling, and infestation by phorid fly larvae.
      Clutch sizes in these populations were lower than all other published reports
      except for the iguana population on the highly xeric island of Curacao, implying
      that adult females in our area are unusually small. We argue that this is more
      likely the result of the exploitation of these populations rather than an
      adaptive response to environmentally extreme conditions.

PMID- 15162700
TI  - Pharmacological activity of the essential oil of Satureja viminea (Lamiaceae).
AB  - The aqueous extract and the essential oil of Satureja viminea (Lamiaceae) were
      tested. General physiologic effects were assessed through the Hippocratic
      screening test. Non fasted female Sprague Dawley rats were utilized and 250, 500,
      750 and 1000 mg/kg doses were used. Two animals were used for each dosage level
      and for the vehicle alone. Exploratory behavior and curiosity were measured using
      a hole board apparatus and placing non-trained mice on the board and recording
      the number of holes explored in a 5 minute period. The Boissier chimney test was
      used to evaluate motor coordination. Muscle strength was assessed through a
      grasping test where mice were hung by their fore-limbs 40 cm above the base on a
      horizontal metal stainless bar. In all these tests, 3 groups of 6 albino mice,
      were treated with 1000 mg/kg of each the essential oil of S. viminea, the vehicle
      and diazepan (1 mg/kg) as a positive control. Analgesic activity was explored in
      Sprague-Dawley rats. The tail flick method described by D'Amour and Smith (1941)
      modified by CYTED was implemented on three groups (6 rats each) of animals
      treated with, each the essential oil of S. viminea (1000 mg/kg), the vehicle and
      indomethacine. The test was carried out just before and 30, 60 and 120 min after
      oral treatment. Peristaltic activity was measured in albino mice, three groups of
      6 animals each, treated orally with each the essential oil of S. viminea (1000
      mg/kg), the aqueous extract (1000 mg/kg), and the vehicle. The marker used was
      activated carbon. Animals were sacrificed 30 min after the marker was given and
      the percent of total small intestine traversed by it was calculated. Also a
      lethal dose 50 (LD 50) was determined with the Spearman-Karber method. A dose
      related spontaneous motor activity reduction was observed. Exploratory behavior
      and curiosity were diminished. The grasping strength of mice was reduced. A very
      clear and significant analgesic effect was observed with the oral administration
      of the essential oil of S. viminea (1000 mg/kg). This effect is compared to that
      of indomethacine. Intestinal transit and gastric emptying were inhibited by the
      essential oil. The LD50 of the essential oil of S. viminea is 556.8 mg/kg.

PMID- 15162701
TI  - Isolation of bothrasperin, a disintegrin with potent platelet aggregation
      inhibitory activity, from the venom of the snake Bothrops asper.
AB  - The venom of Bothrops asper induces severe coagulation disturbances in
      accidentally envenomed humans. However, only few studies have been conducted to
      identify components that interact with the hemostatic system in this venom. In
      the present work, we fractionated B. asper venom in order to investigate the
      possible presence of inhibitors of platelet aggregation. Using a combination of
      gel filtration, anion-exchange chromatography, and reverse-phase high performance
      liquid chromatography, we isolated an acidic protein which shows a single chain
      composition, with a molecular mass of approximately 8 kDa, estimated by SDS
      polyacrylamide gel electrophoresis. Its N-terminal sequence has high similarity
      to disintegrins isolated from different snake venoms, which are known to bind to
      cellular integrins such as the GPIIb/IIIa fibrinogen receptor on platelets. The
      purified protein exerted potent aggregation inhibitory activity on ADP-stimulated
      human platelets in vitro, with an estimated IC50 of 50 nM. This biological
      activity, together with the biochemical characteristics observed, demonstrate
      that the protein isolated from B. asper venom is a disintegrin, hereby named
      "bothrasperin". This is the first disintegrin isolated from Central American
      viperid snake species.

PMID- 15162702
TI  - Esophageal diverticula: current classification and important complications.
AB  - Esophageal diverticula, although often asymptomatic or discovered incidentally
      during the workup of unrelated symptoms, may serve as a sign to clinicians of an
      ongoing dysmotility process involving the esophagus, particularly in our aging
      population. As well, esophageal diverticula may lead to unexpected complications
      as a result of instrumentation such as endoscopy or nasogastric tube placement
      that may result in significant morbidity and mortality including esophageal
      perforation. This article discusses these topics in detail with special emphasis
      on radiologic diagnosis and information for clinicians for management and
      avoidance of potentially serious complications.

PMID- 15162703
TI  - Just a cellulitis.

PMID- 15162704
TI  - Putting the car in the garage: a medical analogy for sexual dysfunction.

PMID- 15162705
TI  - Looking back: president's address in 1914.

PMID- 15162706
TI  - Timely antibiotic therapy for community-acquired pneumonia.

PMID- 15162707
TI  - HIPAA: challenges and opportunities.

PMID- 15162708
TI  - HIPAA: a paradigm shift in the politics of healthcare.

PMID- 15162709
TI  - HIPAA: reviewing the game films.

PMID- 15162711
TI  - To use, or can I use? Now that is the question!

PMID- 15162710
TI  - Information security strategies for healthcare: Part I.

PMID- 15162712
TI  - Data analytics throughout the healthcare enterprise.

PMID- 15162713
TI  - CPOE and pharmacy: can we talk?

PMID- 15162714
TI  - Single Logon: balancing security and healthcare productivity.
AB  - Mayo Single Logon (MSL) has faced the traditional dilemma that is painful to all
      IT organizations because it forces the tradeoff between user productivity and
      security. Recent regulatory initiatives, such as HIPAA, have caused the issue of
      security to take on more importance, forcing organizations to revisit the balance
      of security and productivity. MSL is a security application that brokers user
      credentials and facilitates desktop security. The simple design, functionality
      and stability have allowed MSL to speed up user productivity, keep satisfaction
      high and help solve many security initiatives.

PMID- 15162715
TI  - How the University of Michigan Health System finds opportunity in HIPAA.
AB  - The University of Michigan Health System has dealt with some difficult challenges
      as a healthcare entity covered by the HIPAA Transaction and Code Sets regulation.
      It has processed electronic healthcare transactions for several years and faced
      major system changes to meet the standards. A capital investment in system
      upgrades and new purchases was inevitable. The organization invested in a systems
      infrastructure that provides for real-time application integration, which lays
      the foundation for real-time eligibility and claims processing where health plan
      systems can communicate with healthcare provider systems.

PMID- 15162716
TI  - Privacy: after the compliance date.
AB  - This article reviews successful strategies in preparing for HIPAA Privacy
      compliance. There are ongoing challenges organizations will face after the
      compliance date, such as managing research issues, identifying all business
      associates and managing the accounting of disclosures process. Finally, health
      information professionals must play an active role in ensuring that patient
      information is protected, while providing appropriate access as new uses for
      information are developed.

PMID- 15162718
TI  - HIPAA implementation: measuring change and quality improvement.
AB  - Implementing appropriate practices to achieve compliance with HIPAA regulations
      is a multifaceted task. Implementation is a work in progress because the
      regulations are in various stages of release. As complex working environments,
      healthcare organizations must consider the individual roles of their staff in
      devising an appropriate and effective HIPAA strategy.

PMID- 15162717
TI  - HIPAA: the critical role of identity and access management.
AB  - Whether providing patients with online access to their medical records or
      enabling physicians to place paperless orders, there are several benefits to
      online electronic systems that ultimately can lead to improved patient care and
      outcomes. However, as healthcare providers move closer to a paperless environment
      and Internet-based applications, they must understand the increased risks to
      privacy and security that are incurred by using electronic systems. Organizations
      must give careful consideration to ensure that applications, authentication,
      authorization and provision practices are addressed to ensure HIPAA regulations
      are met and, more importantly, that patient care is not compromised.

PMID- 15162719
TI  - Maximizing the return on investments in information technology by incorporating
      best practices.
AB  - Most system administrators know what needs to be done to make their systems
      secure and manageable but these needs are tough to sell to upper management in a
      tight economy. However, system administrators using industry accepted best
      practices can calculate a return on investment for budgeting purposes, justifying
      expenses by comparing them with expected costs if such practices are not in
      place.

PMID- 15162720
TI  - HCA Inc.: standardization in action.
AB  - Ongoing government and healthcare industry initiatives clearly indicate that
      information technology will be the driver for change in healthcare. As systems
      proliferate, healthcare organizations grapple with issues of whether to choose
      best-of-breed systems or standardize around one vendor. For many years, HCA Inc.
      has been a major proponent of standardization to help meet its financial and
      patient safety objectives. This article examines HCA's experience and explores
      how standardization has been a major factor in the company's financial and
      clinical success, enabling faster implementation, greater quality control and
      significant cost-savings.

PMID- 15162721
TI  - The evolution and implementation of a pediatric computerized order entry system:
      a case study.
AB  - Implementing CPOE is not an easy undertaking. Designing and implementing a
      pediatric-focused CPOE presented a unique challenge because of the age and weight
      considerations inherent with a pediatric patient population. Through the
      experiences involved in an implementation, key elements of a successful
      implementation include high-level sponsorship, involvement of clinicians up-front
      in the process, excellent communication and round-the-clock support. When
      everyone works together with common objectives, milestones are met, and goals are
      realized.

PMID- 15162723
TI  - The aqueous extract of Triumfetta semitriloba (Tiliaceae) does not inhibit the in
      vitro hydrolytic activity of the major pancreatic enzymes.
AB  - The aqueous extract of Triumfetta semitriloba is part of the Costa Rican folk
      pharmacopoeia. It shows no in-vitro inhibitory action on the hydrolytic activity
      of porcine pancreatic amylase, lipase or proteases, thus diminishing the concern
      of intestinal malabsorption in human beings.

PMID- 15162722
TI  - [Venom of Latrodectus mactans from Chile (Araneae, Theridiidae): effect on smooth
      muscle].
AB  - The venoms of Latrodectus sp. have been reported to induce contraction probably
      mediated by adrenergic and cholinergic transmitters. We have demonstrated that
      the venom of Chilean Latrodectus mactans contains neurotoxins that induce a
      contraction partially independent of transmitters release. Transmembrane mobility
      of Na+ and Ca2+ ions and more specifically, the increase of cytoplasmic calcium
      concentration are responsible for tonic contraction in smooth muscle. Calcium may
      enter the cell by several ways, such as the voltage-dependent Ca2+ L-type
      channels and the Na+/Ca2+ exchanger. This study aimed to examine the
      participation of this exchanger in the tonic contraction of smooth muscle in vas
      deferent of rat induced by the venom of the Chilean spider L. mactans. Blockers
      of Na+ channels (amiloride) and Ca2+ L-type channels (nifedipine), and a
      stimulator of the exchanger (modified Tyrode, Na+ 80 mM) were used.
      Simultaneously, variations of the cytoplasmic concentration of Ca2+ were
      registered by microfluorimetry (Fura-2 indicator) in the presence of nifedipine.
      In presence of amiloride, dose-dependent inhibition of venom-induced contraction
      was observed, suggesting the participation of voltage-dependent Ca2+ L-type
      channels. The contraction was only partially inhibited by nifedipine and the Ca2+
      cytoplasmic concentration increased, as assessed by the microfluorimetric
      registration. Finally, the venom-induced contraction increased in the presence of
      modified Tyrode, probably due to the action of the Na+/Ca2+ exchanger. Taken
      together, our results support the idea that the Na+/Ca2+ exchanger is active and
      may be, at least in part, responsible for the contraction induced by the venom of
      Chilean L. mactans.

PMID- 15162725
TI  - [Gametophyte morphogenesis of Mexican species of Pleopeltis (Polypodiaceae,
      subfamily Pleopeltoideae)].
AB  - The development and morphology of the gametophytes of seven species of ferns from
      genus Pleopeltis are described and compared. The spore germination is Vittaria
      type in P. astrolepis, P. crassinervata, P. macrocarpa, P. polylepis and P.
      revoluta. For P. angusta and P. mexicana it was proposed a new germination
      pattern is Pleopeltis-type. The prothallial development is Drynaria-type in P.
      astrolepis, P. crassinervata, P. macrocarpa, P. polylepis and P. revoluta and
      Ceratopteris-type for P. angusta and P. mexicana. The gametangia are typical of
      the leptosporangiate ferns, sporophytes after six and a half months in culture
      did not appeared.

PMID- 15162724
TI  - [Effect of arthropod extracts on the multiplication of Toxoplasma gondii in mouse
      peritoneal macrophages].
AB  - Treatment of toxoplasmosis usually causes secondary effects. It is important to
      find active substances extracted from natural organisms. In this work we studied
      some arthropod extracts that have effect against Toxoplasma multiplication inside
      mouse macrophages. After studying 382 extracts, 23 were selected on the basis of
      the activity and we found that 13 extracts from orders Polydesmida, Lepidoptera,
      Orthoptera and Hymenoptera exerted an important inhibition of Toxoplasma
      multiplication.

PMID- 15162726
TI  - [Anatomy and uses of the mature leaves of three species of Sabal (Arecaceae) of
      the Yucatan, Mexico].
AB  - This paper describes the leaf anatomy of Sabal mauritiiformis (Karst.) Griseb. &
      H. Wendl., Sabal mexicana Mart. and Sabal yapa Wright ex Becc., three of the four
      most representative species of the Yucatan Peninsula, in Mexico. These species
      are locally used: in the roofing of traditional homes, as food (fruits and apical
      buds), and in the production of hats, brooms and handicrafts. Leaf samples were
      collected in secondary growth of lower montane rainforest in the state of
      Quintana Roo and in two home gardens in the state of Yucatan. Herbarium samples
      were obtained, and samples of blade and petiole were fixed in formaline-acetic
      acid-alcohol. Cross incisions were made on the blade and petiole, and were dyed
      with safranin and toluidine blue O. The results show that S. mauritiiformis and
      S. yapa are morphologically alike: both are tall, slim palm trees; the leaf in S.
      mauritiiformis is a shorter palm-like structure compared with the other two
      species. The shape of the main nerve, as seen in cross section, is rectangular in
      the three species. The hastula in the three species is acuminate and adaxial. The
      foliar anatomic structure is similar in the three species, although there are
      some differences. The adaxial an abaxial epidermis of the blade consist of one
      layer and, superficially, the anticlinal walls are straight; the stomata are
      intercostal, of the tetracytic type, present on both surfaces in S. mexicana and
      S. yapa and only on the abaxial surface on S. mauritiiformis. The hypodermis is
      one layer thick in S. yapa and in S. mexicana and two layers thick in S.
      mauritiiformis. In the three species the palisade parenchyma consists of several
      undefined strata as the cells are similar-in shape and size--to the cells in the
      spongy parenchyma, so there is no marked difference between these strata and the
      spongy parenchyma seems almost continuous. Both fibrous and vascular bundles are
      distributed between the hypodermis and the palisade parenchyma; the fiber bundles
      can be found towards the abaxial surface while the vascular and fiber bundles are
      located towards the adaxial surface. The fibers, in the three species, are
      elongated, with the pointed tips, undivided and unseptated. One to three wide
      vessels of metaxilem can be seen in the vascular bundles, those in S. yapa being
      the widest in diameter. The vascular bundles are surrounded by thick fiber
      sheaths which come in pairs. The anatomic structure of the petiole is similar to
      that of the blade, and is characterized by the many vascular and fiber bundles
      dispersed in the parenchymatous tissue, and which are very resistant. The
      histological structure of the blade and petiole reflects strength and
      flexibility, qualities which make these plants adequate in the construction of
      roofs for rural housing and other buildings.

PMID- 15162727
TI  - Ultrastructural morphologic description of the wild rice species Oryza latifolia
      (Poaceae) in Costa Rica.
AB  - The wild rice species Oryza latifolia is endemic to Tropical America,
      allotetraploid and has a CCDD genome type. It belongs to the officinalis group of
      the genus Oryza. This species is widely distributed throughout the lowlands of
      Costa Rica and it is found on different life zones, having great morphologic
      diversity. The purpose of this research is to perform a morphologic description
      of O. latifolia samples of three Costa Rican localities (Carara, Liberia and
      Canas) and to see if the phenotypic diversity of the species is reflected at the
      ultra-structure level. Structures such as the leaf blade, ligule, auricles and
      spikelet were analyzed. Leaf blade morphology of the specimens from the three
      localities is characterized by the presence of diamond-shaped stomata with
      papillae, zipper-like rows of silica cells; a variety of evenly distributed
      epicuticular wax papillae and bulky prickle trichomes. The central vein of the
      leaf blade from the Canas populations is glabrous, while those from Carara and
      Liberia have abundant papillae. There are also differences among the borders of
      the leaf blade between these locations. Canas and Liberia present alternating
      large and small prickle trichomes ca. 81 and 150 microns, while Carara exhibits
      even sized prickle trichomes of ca. 93 microns. Auricles from Canas are
      rectangular and present long trichomes along the surface ca. 1.5 mm, while those
      of Liberia and Carara wrap the culm and exhibit trichomes only in the borders.
      The ligule from the plants of Carara has an acute distal tip, while that of Canas
      and Liberia is blunt. The Liberia spikelet has large lignified spines while Canas
      and Carara show flexible trichomes.

PMID- 15162728
TI  - How do mangrove forests induce sedimentation?
AB  - The mangrove forests play a significant role as sediment traps. They reduce tidal
      flows and induce sedimentation of soil particles at low tide. However, there are
      no such processes taking place in the non-mangrove areas. Site of Avicennia
      Rhizophora interphase is more efficient than Avicennia and or Rhizophora zones,
      in trapping the sediment by 30, 25 and 20% respectively at low tide as compared
      to high tide.

PMID- 15162730
TI  - [Floral biology, reproductive system and reproductive success of Macroptilium
      fraternum (Fabaceae)].
AB  - Observations about the floral biology and the reproductive system of Macroptilium
      fraternum were made in two populations in Argentina, with different edaphic
      conditions, situated at the southern area of distribution of the species. The
      coexistence of two kind of flowers in the same plant was detected in both
      populations and in herbarium material from other localities: a) cleistogamous
      preanthesis flowers and b) pseudocleistogamous flowers. The cleistogamous
      preanthesis flowers possessed wings longer than 5 mm and were disposed in
      pubescent, erect, racemes exposed above the level of the foliage. The anthesis
      lasted approximately 5 hours on sunny days or 9 hours on rainy days, the right
      wing covered the left wing, the corolla acquired a bilabiate aspect, offering the
      left wing as landing platform; they produced a low quantity of nectar (0.18 +/-
      0.13 microliter); they did not receive pollinator visits; approximately four
      hours after the beginning of the anthesis on sunny days the ovary started to
      grow; in the bud, the receptive stigma was covered with germinating pollen grains
      from the same floral unit. The pseudocleistogamous flowers possessed wings
      shorter than 5 mm that were disposed in brief, hirsute and prostrate racemes, non
      subterranean as in other Macroptilium species; the banner started to spread
      exposing partially the wings, the left wing limb surrounded the keel and never
      spread; the right wing started to spread and after 2 seconds refolded and began
      to wither, the ovary began to grow immediately; the flower did not offer a
      surface to allow visitors to settle; in the buds the stigma was receptive and
      found with pollen grains from the same floral unit emitting their tubes. The
      relative reproductive success was low (natural pollination = 8%; spontaneous self
      pollination = 3%), probably due to the low pollen viability, the high percentage
      of seed abortion and the lack of pollinator's visits. The production of both
      flower types is not conditioned by edaphic factors, as they were found in plants
      belonging to different environments. Study of the progeny of both floral types in
      both populations has demonstrated that each one produces a similar amount of
      seeds contributing to the next generation with plants of similar characteristics
      (slow development, low resistance to infections and high mortality). The absence
      of pollinators in these flowers (in part because they preferred to visit flowers
      of other species with more reward and in part because of the fragmentation of the
      habitats), would be producing inbreeding depression in the studied populations;
      if the germplasm variability is not preserved, these populations situated at the
      Southern end of the distribution range of the species could become extinguished.

PMID- 15162731
TI  - [Limnology of high mountain tropical lake, in Ecuador: characteristics of
      sediments and rate of sedimentation].
AB  - Equatorial high mountain lakes are a special type of lake occurring mainly in the
      South American Andes as well as in Central Africa and Asia. They occur at
      altitudes of a few thousand meters above sea level and are cold-water lakes (< 20
      degrees C). Relatively little is known about them. A long-term limnological study
      was therefore undertaken at Lake San Pablo, Ecuador, to analyze the basic
      limnological processes of the lake, which has a tendency for eutrophication.
      Sediment quality of San Pablo Lake is given under consideration of horizontal and
      vertical distribution using sediment cores. Significance of sediments for
      eutrophication process of lakes is demonstrated using phosphorus concentration of
      sediments as well as the phosphorus retention capacity of the sediments by ratio
      Fe/P. Dating of the sediments is done using 137Cs and 210Pb, but the activity of
      137Cs in the sediment was very low nearly at the detection level. Sedimentation
      rate is determined to be 3.5 mm/year and the sediment cores represent about 110
      years. P concentration of the sediments is high (approximately 5 g/kg dry
      substance), and P retention capacity by Fe is insufficient (Fe/P = 4). The
      sediment quality did not change significantly during the past decades, and the
      trophic state of San Pablo Lake was already less or more eutrophic 110 years ago.
      The contamination of the lake sediments by heavy metals is insignificant.

PMID- 15162732
TI  - Zooplankton associations and environmental factors in Ogunpa and Ona rivers,
      Nigeria.
AB  - Zooplankton abundance, composition and environmental parameters were monitored in
      two tropical rivers over a twenty month period. The data was subjected to
      cluster, factor and correlation analysis to determine the grouping pattern of
      zooplankton and their relationship to environmental parameters. Environmental
      factors in Ogunpa and Ona rivers--included buffering capacity, trace metal ions,
      pH-temperature/transparency--were primarily influenced by rainfall. The dominance
      of the Rotifera in both rivers was attributed to their short developmental rate
      and fish predation on larger zooplankton. Two groups of associations were
      identified in each river--a commonly occurring species group exhibiting strong
      homogenous correlation with environmental factors and a predominant group
      exhibiting weak correlation with environmental factors and whose
      abundance/composition may be defined by biotic factors.

PMID- 15162729
TI  - [Structural characterization of a Podocarpus parlatorei and Juglans australis
      forest in Salta, Argentina].
AB  - Stands of Subtropical Montane Cloud Forest were studied in areas under different
      land use regimes near Los Toldos (NW Argentina). Circular plots were used to
      calculate density and basal area of trees with dbh > 10 cm; and density of trees
      with dbh < 10 cm. The stands were classified and grouped as a function of basal
      area. Five structures were recognized, with different proportions of Juglans
      australis, Podocarpus parlatorei and shade-tolerant species like Blepharocalyx
      salicifolius, Allophylus edulis and Myrcianthes sp. Less disturbed area stands
      had a higher basal area and greater dbh for all species, and shade-tolerant
      species in the canopy. In the most disturbed area, all canopy species were shade
      intolerant and regeneration was dominated by shade-tolerant species. The
      differences in composition, basal area, stem diameter class distribution and
      regeneration indicate that the structure types corresponded to different stages
      of the successional process, and the regeneration of the most disturbed areas
      suggest a tendency towards the composition of mature forest.

PMID- 15162733
TI  - Combined effect of concentrations of algal food (Chlorella vulgaris) and salt
      (sodium chloride) on the population growth of Brachionus calyciflorus and
      Brachionus patulus (Rotifera).
AB  - Salinity is an important variable influencing the density and diversity of
      rotifers. Studies on salt tolerance of rotifers have so far concentrated on
      euryhaline species while very little information is available on non-euryhaline
      taxa. In the present work, we have evaluated the combined effects of Chlorella
      vulgaris and sodium chloride on the population growth of two freshwater rotifers
      B. calyciflorus and B. patulus. A 24 hr acute tolerance test using NaCl revealed
      that B. calyciflorus was more resistant (LC50 = 3.75 +/- 0.04 g l-1) than B.
      patulus (2.14 +/- 0.09 g l-1). The maximal population density (mean +/- standard
      error) for B. calyciflorus in the control at 4.5 x 10(6) cells ml-1 (algal level)
      was 80 +/- 5 ind. ml-1, which was nearly a fifth of the one for B. patulus (397
      +/- 7 ind. ml-1) under comparable conditions. Data on population growth revealed
      that regardless of salt concentration, the density of B. calyciflorus increased
      with increasing food levels, while for B. patulus, this trend was evident only in
      the controls. Regardless of salt concentration and algal food level, the day of
      maximal population density was lower (4 +/- 0.5 days) for B. calyciflorus than
      for B. patulus (11 +/- 1 day). The highest rates of population increase (r
      values) for B. calyciflorus and B. patulus were 0.429 +/- 0.012 and 0.367 +/-
      0.004, respectively, recorded at 4.5 x 10(6) cells ml-1 of Chlorella in the
      controls. The protective role of algae in reducing the effect of salt stress was
      more evident in B. calyciflorus than B. patulus.

PMID- 15162734
TI  - [Morphologic variations in Blackfordia virginica (hydroidomedusae:
      Blackfordiidae) in coastal lagoons of Chiapas, Mexico].
AB  - Blackfordia virginica is an important hydromedusae in the zooplankton of coastal
      lagoons at Mexico. In order to contribute to their study, morphological
      variations of these species were analyzed in the system of coastal lagoons of
      Chiapas, Mexico. A total of 503 jellyfish were studied their sizes varied from
      6.1 to 9.9 mm of umbrelar diameter. The number of marginal tentacles varied from
      86 to 125. A 67.7% females and 30.2% males were recognized. Only 31 jellyfish (26
      females and five males) presented morphological variations of ten different types
      and affected the number and form of the handles, radial channels and gonads. The
      size of the jellyfish and the number of tentacles reflected a correlation of
      0.74.

PMID- 15162735
TI  - [Diversity and abundance of molluscs in Thalassia testudinum prairie of the Bay
      of Mochinma, Mochima National Park, Venezuela].
AB  - The diversity and abundance of benthic malacological communities associated to
      Thalassia testudinum beds was studied at four localities of Mochima Bay, Sucre
      state, Venezuela. At each locality, samples were taken monthly on perpendicular
      transect at different depths (0-4 m), from January 1991 to December 1991, using a
      quadrate (0.25 m2) for collecting mollusks and sediments. A total of 2,988
      organisms of infauna and epifauna belonging to 81 species of the classes
      Gastropoda (41) and Bivalvia (40) were collected. More abundant species were
      Anadara notabilis, Codakia orbicularis, Cerithium litteratum, Cerithium eburneum,
      Batillaria minima, Modiolus squamosus, Modulus modulus, Chione cancellata,
      Turritella variegata, Arca zebra, y Laevicardium laevigatum. There were
      significant differences in number of organisms between depth and month at La
      Gabarra which presented the highest value of total (4.51 bits/ind) and monthly
      diversity (2.71-3.90 bits/ind). Biomass and abundance were low in the Mochima Bay
      while Varadero station presented the highest value. The bivalve A. notabilis and
      gastropod M. modulus were species common to the four stations.

PMID- 15162738
TI  - Revision of the Natada fusca complex and description of six new neotropical
      species (Lepidoptera: Limacodidae).
AB  - Six new species in the genus Natada, which have been hidden under Natada fusca
      Druce, are described and defined primarily by genitalia. New species include N.
      burnsi, N. truncata, N. singulara, N. chaconi, N. covelli, and N. confusa. Five
      of eight species in the Natada fusca complex, which also includes N. fuscodivisa
      Dognin, occur in Costa Rica. Distribution of the complex ranges from Mexico to
      the upper Amazon Basin and Guianas. Detailed geographic information and multiple
      genitalic drawings of males of one species, N. confusa, are provided to help
      define and separate species. The lectotype and paralectotype of N. fusca are
      designated.

PMID- 15162736
TI  - [Relative frequency of Boophilus microplus (Acari: Ixodidae) in bovines (Bos
      taurus and B. indicus) in 8 ecological zones of Costa Rica].
AB  - The research on the relative abundancy of Boophilus microplus took place in ten
      farms, distributed in eight ecological zones (EZ) and two rainfall systems of
      Costa Rica. Monthly visits were made to pick up ticks larger than 4 mm from the
      right side of the animals. The total number of ticks was increased by two and
      divided between the total of sampled bovines per farm. Farm visits were adjusted
      to animals bath to allow the recovery of the tick population. B. microplus was
      detected in all sampled farms throughout the year. Media comparison statistic
      analyses were made and no differences were found among EZ, farms and seasons. On
      the contrary, there were important statistical differences between rainfall
      systems. The rainfall system 1, that included rain seasonality, showed larger
      tick infestations (p = 0.03). An isothermal and low variability regarding
      relative humidity situations were present in some of the areas included in this
      research. Bath intensity was lower to other past studies. Even though no
      differences were found between production systems, it is important to emphasize
      that bath intensity was higher in european cattle farms, in comparison to others
      of the same EZ, but of crossbred. A tick manual removable system was recommended
      in dual-purpose and specialized dairy farms with no more than 30-35 animals, as
      an alternative feasible system that significantly reduced acaricide use.

PMID- 15162737
TI  - [Relative abundance of Amblyomma spp. (Acari: Ixodidae) in bovines (Bos taurus
      and B. indicus) from Costa Rica].
AB  - The research describe the big amount of ticks of the Amblyomma genus, found on
      bovines through monthly samplings carried out in ten farms in eight ecological
      zones (EZ) of Costa Rica. Ticks larger than 4 mm were picked up from the right
      side of the animals during the visit. The study compiled meteorological
      information for some farms located in the experiment, showing that the most
      fluctuant variable is rainfall. The most important Amblyomma species found was A.
      cajennense. Amblyomma nymphs were found only from January to May, which coincides
      with the lower humidity season in the rain seasonality area; as for it is
      expected only one generation per year. In the lab work Amblyomma nymphs are kept
      to measure the moulting season and the surviving time under controlled
      conditions, but no major differences were found between both sexes. The surviving
      periods show that it is not possible to do a grazing land handling, in order to
      control this genus species. Adults of the genus Amblyomma are present through all
      the year, not showing any specific preference for a season. The research divided
      the investigation areas in rain seasonability and not-seasonality systems. The
      highest amount of Amblyomma is found given in the rain seasonality system or of
      pacific influence. A. maculatum is present only in the EZ of Tropical Humid
      Forest transition to pre-mountainous. Likewise, Ixodes boliviensis is found in
      the EZ of low mountainous Very Humid Forest.

PMID- 15162739
TI  - Life history of Manataria maculata (Lepidoptera: Satyrinae) from Costa Rica.
AB  - The life history and early stages of the satyrine butterfly Manataria maculata
      are described and illustrated from Costa Rica. Eggs are laid on Lasiacis sp.
      (Panicoideae), a new non-bamboo host plant for the genus Manataria. The larval
      stage varied from 23 to 28 days, and the pupal duration was approximately 12 days
      when reared on Bambusa vulgaris and Guadua angustifolia in captivity at 23-24
      degrees C.

PMID- 15162741
TI  - Larval, pre-juvenile and juvenile development of Diapterus peruvianus
      (Perciformes: Gerreidae).
AB  - The development of Diapterus peruvianus (Sauvage 1879) is based on 60 larvae
      collected in superficial tows made in Bahia Concepcion, and on 16 pre-juvenile
      and juvenile organisms collected in Bahia de La Paz, B. C. S., Mexico, using a
      standard plankton net and a rectangular epibenthonic net, respectively. Larvae of
      D. peruvianus show three large blotches on the dorsum of the gut that can fuse
      together and give the appearance of one large continuous blotch. There are two to
      three pre-anal pigments and 16 post-anal pigments in the ventral midline;
      cephalic pigments are present from the postflexion stage, as well as a serrated
      preoperculum. The pre-juvenile and juvenile organisms are distinguished by their
      body depth, the anal-fin formula, the serrated pre-operculum and the base
      pigments in the dorsal and anal fins.

PMID- 15162742
TI  - [Gonadal development and reproductive cycle of Lutjanus peru (Pisces: Lutjanidae)
      in Guerrero, Mexico].
AB  - In this paper, aspects of the reproductive biology of Lutjanus peru that can be
      used for the fishery management are described. Samples were taken monthly in 1993
      and 1994, from commercial catches in the southern coast of Guerrero, Mexico. A
      global sex ratio of 1:1.37 (M:F) was found, but the sex ratio was highly variable
      each month. The condition factor, gonadosomatic, hepatosomatic and stomach
      fullness indexes were analyzed. None of the morphophysiological indexes showed
      any clear tendency. From 377 gonads, both male and female, five developmental
      stages were characterized for each sex. L. peru shows asynchronous gonad
      development and multiple spawning. Two spawning period were observed in 1993
      (March, and August-September) and three in 1994 (April-May, July-August, and
      November), with a maximum in August of both years. Length at first maturity for
      the females of L. peru was estimated at 295 mm fork length.

PMID- 15162740
TI  - [Environmental variables and abundance of eggs of Anchoa mitchilli (Pisces:
      Engraulidae) in Tamiahua lagoon, Mexico].
AB  - Egg abundance of Anchoa mitchilli was studied in Laguna de Tamiahua, Veracruz
      during three annual cycles (84-85, 85-86 and 86-87). Our goal was to detect areas
      and seasons with high egg abundance and the possible association of such areas
      and seasons with covariates such as temperature, salinity, transparency, depth,
      location, season and year. The association was tested statistically using a
      Generalized Linear Model (GLM) with Gamma type error. The results suggest that
      not all the covariates considered have a significant effect on egg abundance
      (Student's T, p > 0.005). The significant effects show the presence of a seasonal
      component and that the effect of salinity on egg abundance is conditional to
      location. High average egg abundances for the three annual cycles were observed
      during summer. The presence of significant interactions (Student's T, p < 0.05)
      during the last two annual cycles shows that the variability of egg abundance is
      associated to surface temperature and salinity, conditionally to year.

PMID- 15162743
TI  - [Food habits of Lutjanus peru (Pisces:Lutjanidae) in the coasts of Guerrero,
      Mexico].
AB  - In this paper we describe the feeding habits of the Red snapper (Lutjanus peru)
      in the southern coast of Guerrero state, Mexico. This data could be relevant to
      local fisheries management. In total 385 full stomachs (206 from females and 179
      from males) were collected monthly in 1993 and 1994, from commercial catches.
      Stomach contents were identified to species level when possible. Food items were
      grouped into taxonomically coherent groups, and their numbers, weight and
      frequency of occurrence obtained. The index of relative importance (IRI) was
      calculated for the total sample, by month, sex and size class. In 1993, a total
      of 42 different food items were obtained, and 43 in 1994. Food items consisted of
      fishes, crustaceans, and mollusks. The grouping of prey species, genera, or
      families rendered 14 food groups, as follows: Mollusks, Amphipods, Copepods,
      Stomatopods, Penaeus vannamei, Brachiuran Larvae, Stomatopods Larvae, Family
      Albuneidae Larvae, Other crustaceans, Anchoa ischana, Anchoa lucida, Other
      fishes, Salps and Unidentified organic matter. Anchoa ischana dominated the
      trophic spectrum in both years. Although, Amphipods, Anchoa lucida and Other
      fishes had important indexes in 1994. There was high variability in the diet
      composition by month. Nevertheless, in 1993, from February to August, crustaceans
      as a whole dominated the diet. In 1994, crustaceans only dominated in March and
      August. No differences in food habits were found between immature fish, males and
      females. The diet of the Red snapper varies as they grow, although the same food
      groups are found always. At the adult phase, in length classes over 261 mm FL,
      there is some degree of specialization, as they consume more fish, particularly
      engraulids.

PMID- 15162744
TI  - Age determination of Anisotremus interruptus (Perciformes: Haemulidae) by scale
      reading, in the coast of Colima, Mexico.
AB  - This paper deals with the age determination in Anisotremus interruptus by reading
      of scales that allowed the identification of 9 age groups. The width of the
      growth rings diminishes as the age increases. The growth of the scales is
      proportional to the fish growth. The period of highest growth rate happens during
      the first year of life. During the first year A. interruptus grows 12.52 cm, the
      second year 4.95 cm and the third, 4.60 cm. The strategy of the quick growth
      during the first year of life allows A. interruptus to diminish the natural
      mortality.

PMID- 15162745
TI  - Four new species of eastern tropical Pacific jawfishes (Opistognathus:
      Opistognathidae).
AB  - Three of four new jawfishes described herein have sexually dimorphic jaws and
      dichromatic maxillary markings: O. smithvanizi, with a simple nasal cirrus,
      buccal pigmentation and other traits similar to members of the O. macrognathus
      group, is known only from Isla del Cano, a continental shelf island off southern
      Costa Rica; O. fossoris, with a multifid nasal cirrus, a broad dorsal membranous
      subopercular flap and a black spot on tips of first dorsal-fin spines lives in
      the Gulf of California and is a sister-species of O. galapagensis, the maxilla of
      O. walkeri terminates in a flexible scimitar-shaped lamina in adults of both
      sexes, but is longer in males, the species lacks nasal cirri and is also
      restricted to the Gulf of California. Opistognathus brochus is a small species
      with dark speckling on head and body, and several dark blotches along the dorsal
      fin and two bars on the tail; it is found in moderately deep water on the Costa
      Rican coast and Gulf of California. Opistognathus mexicanus is placed in the
      synonymy of O. punctatus. Opistognathus galapagensis, O. rhomaleus and O.
      fenmutis are recorded for the first time from Costa Rica and a description of the
      latter is given and an identification key and summary table are provided for all
      known eastern Pacific species of Opistognathus.

PMID- 15162746
TI  - [Fauna from the M/N "Vikheim"ship exploration in the northwest of the Colombian
      Caribbean].
AB  - Crustaceans (5 families, 10 species) and fish (38 families, 101 species) were
      captured (October 27 through November 3, 1979) from the R/V "Vikheim" (Cruise
      7901) in the Colombian Caribbean, at a 10-630 m, depth range (Metapeneopsis
      shrimp, 26 species of fishes new for the trawling bottom and, Squalus cubensis,
      Chlorophthalmus agassizi, and, Neoepinnula orientalis), new fishes records for
      the Caribbean of Colombia.

PMID- 15162747
TI  - Lunar phase and catch success of the striped marlin (Tetrapturus audax) in sport
      fishing at Los Cabos, Baja California Sur, Mexico.
AB  - The influence of the lunar phases on the catch-per-unit effort (CPUE) of the
      striped marlin (Tetrapturus audax) captured by the Cabo San Lucas, Baja
      California Sur, Mexico sport-fishing fleet from October 1987 to June 1989 was
      analyzed. The information is from 3,377 fishing trips by 13 vessels that
      represent about 10% of the fleet. The analysis of the CPUE showed a maximum in
      January 1988 and a minimum in February 1989. Taking into account the knowledge of
      the factors that had influence on the fishing success is important in the
      resource management. No significant difference during the full moon compared with
      results during other lunar phases was found.

PMID- 15162748
TI  - Distribution and abundance of Syacium ovale larvae (Pleuronectiformes:
      Paralichthyidae) in the Gulf of California.
AB  - The spawning season of the tonguefish Syacium ovale (Gunter 1864) was determined
      by an analysis of the distribution of preflexion stage larvae in the Gulf of
      California. The larvae were collected during eight oceanographic surveys between
      1984 and 1987. The spawning of this species starts in early summer and ends at
      the beginning of fall, with the highest reproductive activity in mid summer. The
      central and southern regions of the Gulf are the most important reproductive
      area. Spawning is associated with high sea surface temperatures and low plankton
      biomass, both of which are characteristics of the tropical current that invades
      the study area during summer.

PMID- 15162749
TI  - [Distribution and abundance of Caiman crocodilus in the Cano Negro National Wild
      Life Refuge, Costa Rica].
AB  - The distribution and abundance of a population of Caiman crocodilus fuscus were
      estimated by monthly counting of eye-shines at night, from February 1999 to March
      2000 in six transects of Rio Frio in the Cano Negro National Refuge (RNVSCN),
      Northern Costa Rica. March was the month with the greatest abundance of caimans
      observed. The visible fraction of the population (PV2 index) fluctuated between
      42.59% to 54.71% during the wet season and 35.49% to 53.93% in the dry season.
      The transects of river with greater abundance of caimans were Terron-Sabogal and
      Sabogal-Playuela. Significant differences were determined in the abundance of
      caimans between transects, except the transects Entrada San Sebastian-Las Cubas
      and Las Cubas-Entrada Cano Los Patos and Entrada Cano Los Patos-Terron and Boca
      Sabogal-Playuela. The population of estimated brown caiman in this study was
      2283.48 +/- 313.5. The statistical analysis by seasons did not show significant
      differences in the number of caimans observed. Estimated mean number of caimans
      per km of river was 74.36/km for 30.7 km of habitat. The results of this study
      indicated that the fluctuation in population density during the seasons is
      attributable to local movements.

PMID- 15162750
TI  - [Diet of the capybara Hydrochaeris hydrochaeris (Rodentia: Hydrocharidae) in Cano
      Limon, Arauca, Colombia].
AB  - We studied the composition and seasonal variation of the diet of the capybara
      (Hydrochaeris hydrochaeris) in the flooded savannas of Cano Limon, Colombia. This
      was achieved by direct observation of the consumption patterns of these animals.
      The capybaras only consumed plants, and their diet included 89 species of 22
      families. Sixty three percent of these plant species had not been reported
      before. The most commonly consumed plants (94% of the diet), belonged to the
      Poaceae, Cyperaceae, Leguminosae and Pontederiaceae. Only seven species
      represented 60% of the total diet: the grasses Hymenachne amplexicaulis (16.9%),
      Digitaria bicornis (4.5%) and Panicum maximum (4.4%) and the Cyperaceae
      Rynchospora corymbosa (4.4%). There was seasonal variation in the diet
      composition of capybaras.

PMID- 15162752
TI  - Dare we use the word (gasp)--"rationing"?

PMID- 15162751
TI  - [Ecological affinity and current distribution of primates (Cebidae) in Campeche,
      Mexico].
AB  - We carried out surveys realized field work from March to September 2000 to get
      the current distribution of Cebids in the state of Campeche, Mexico. Based on
      interviews and direct observations. We defined the distribution of Ateles
      geoffroyi yucatanensis and Alouatta pigra and we documented the first time
      localities where Allouata palliata is found in the state. We made distributional
      maps of each species using vegetation overlays from Inventario Nacional Forestal
      (Inv For) and each point documented during fieldwork. We presented the
      distribution of species according to confiability of the verified or expected
      data. Using the attributes table of Inv For, we calculated the areas of
      distribution which were 22,735 km2 for Alouatta sp. and 18,501 km2 for A. g.
      yucatanensis. We also presented the area occupied by each species according to
      vegetation types and the relative proportion of these vegetation types in the
      state. We confirmed the ability of Alouatta sp. to survive in disturbed
      environments produced by habitat fragmentation, and the affinity of A. g.
      yucatanesis to well preserved habitats.

PMID- 15162753
TI  - 3 steps to profitable managed care contracts.
AB  - An effective managed care contract negotiation strategy should be founded on:
      Internal analysis that compares performance of your current managed care
      contracts in terms of volume versus discount rates and volume versus profit.
      External analysis that compares your current contracts with those of competitors
      and assesses prevailing market rates, contract language and provisions, and
      premium trends Payment performance analysis that identifies payment promptness
      and accuracy and associated penalty dollars for each payer.

PMID- 15162754
TI  - Medicare payment monitoring systems: 20 questions.

PMID- 15162755
TI  - How are hospitals financing the future? The future of capital access.

PMID- 15162756
TI  - A capital idea. Bonds and nontraditional financing options.
AB  - Not-for-profit healthcare organizations have four basic sources of capital:
      internal sources, philanthropy, asset sales, and external sources. External
      sources, in particular, offer a wealth of options that are important for such
      organizations--especially those facing significant capital shortfalls--to
      consider. External sources include bond offerings and nontraditional offerings,
      such as receivables financing, off-balance-sheet options, real estate investment
      trusts, and subordinated securities.

PMID- 15162757
TI  - New directions in Medicare managed care.
AB  - The new Medicare Prescription Drug, Improvement, and Modernization Act of 2003
      offers the most sweeping reforms to the Medicare program since its inception. The
      managed care benefit formerly offered by Medicare+Choice is greatly improved
      under Medicare Advantage. Now the nation's senior citizens in urban and rural
      areas alike can participate in PPOs that provide care-management programs and
      protection against catastrophic costs. They also receive the same kind of private
      health insurance options that have been available to the nation's work force.

PMID- 15162758
TI  - So you want to be a CFO?
AB  - If you think that becoming a CFO is a pretty straightforward career path, think
      again. Today's CFO needs much more than the traditional degrees and usual
      certifications to succeed. The path will be smoother if you know the skill sets
      and training needed to become a successful CFO and are prepared for some of the
      pitfalls you're likely to encounter along the way.

PMID- 15162759
TI  - Your capital strategy plan and deliver.
AB  - A comprehensive capital plan can help organizations achieve long-term goals. In
      contrast to previous planning methods that were largely department-driven and
      spanned three-year increments, this approach maintains a strategic focus and
      identifies and prioritizes major capital requirements over a 10-year planning
      horizon.

PMID- 15162760
TI  - An alternative to real estate ownership.
AB  - Partnering with healthcare real estate managers and investors is one way to
      generate capital, improve cash flow, and minimize the management costs of
      developing and operating outpatient properties without sacrificing control of
      strategic locations or facilities. Eight simple steps can help you identify and
      select viable strategic healthcare real estate partners and negotiate effective
      monetization (sale of property title) agreements with them.

PMID- 15162761
TI  - The cost of staying young.

PMID- 15162762
TI  - Maintaining the strength of your convictions.

PMID- 15162763
TI  - First communication, then automation.

PMID- 15162764
TI  - (Coat)tails, you win.

PMID- 15162765
TI  - 21st century treasurers: leveraging assets--and themselves.

PMID- 15162766
TI  - Capital as percentage of total costs declining in U.S. hospitals.

PMID- 15162767
TI  - Linking supply costs and revenue: the time has come.

PMID- 15162768
TI  - [Different terms used to describe "red tides"].
AB  - An event characterized by sudden increase in phytoplankton population, in the sea
      or aqueous environment, is often designated by different Spanish terms that
      attempt to describe the nature, aspect, characteristics, and/or properties of
      such phenomena. In this communication, we discuss the convenience of reaching an
      agreement among the Spanish-speaking scientific community to use a simple Spanish
      term that could be much more informative and accurate when referring to Harmful
      Algal Blooms (HABs), in general. Summarizing the different Spanish terms
      historically employed to describe the proliferation of noxious phytoplankton in
      the sea, we propose "Proliferacion Microalgal Nociva" (PMN = HAB) as a term that,
      on the basis of its etymological meaning could be considered correct. Its use
      could help to avoid the prevailing confusion in our language caused by different
      misleading terms now employed when referring to a Harmful Algal Bloom event.

PMID- 15162769
TI  - Polythene and plastic-degrading microbes in an Indian mangrove soil.
AB  - Biodegradation of polythene bags and plastic cups was analyzed after 2, 4, 6, and
      9 months of incubation in the mangrove soil. The biodegradation of polythene bags
      was significantly higher (up to 4.21% in 9 months) than that of plastic cups (up
      to 0.25% in 9 months). Microbial counts in the degrading materials were recorded
      up to 79.67 x 10(4) per gram for total heterotrophic bacteria, and up to 55.33 x
      10(2) per gram for fungi. The microbial species found associated with the
      degrading materials were identified as five Gram positive and two Gram negative
      bacteria, and eight fungal species of Aspergillus. The species that were
      predominant were Streptococcus, Staphylococcus, Micrococcus (Gram +ve),
      Moraxella, and Pseudomonas (Gram -ve) and two species of fungi (Aspergillus
      glaucus and A. niger). Efficacy of the microbial species in degradation of
      plastics and polythene was analyzed in shaker cultures. Among the bacteria,
      Pseudomonas species degraded 20.54% of polythene and 8.16% of plastics in one
      month period. Among the fungal species, Aspergillus glaucus degraded 28.80% of
      polythene and 7.26% of plastics in one-month period. This work reveals that the
      mangrove soil is a good source of microbes capable of degrading polythene and
      plastics.

PMID- 15162770
TI  - [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from
      Plantago major (plantaginaceae)].
AB  - For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was
      tested in 20 male NGP mice, with an average weight of 20.15 g and separated in
      two groups of ten individuals each. The dose used was 2000 mg/kg and the control
      group received 0.5 ml of distilled water. The extract administration was done
      daily during five days at week for a total period of 40 days. Signs of sub
      chronic toxicity were observed in the days two and 12 of treatment. No
      significant change in corporal weight was observed. The ocular irritation was
      tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The
      dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major
      leaves, instill into the right eye and the control was used the left eye instill
      200 microliters of distilled water. The administration was done daily during five
      days. The extract shows no significant irritation during the observation period.

PMID- 15162771
TI  - In vitro multiplication of Toxoplasma gondii and Trypanosoma cruzi in mouse, rat,
      and hamster astrocytes.
AB  - The infection and multiplication of Toxoplasma gondii and Trypanosoma cruzi were
      compared in primary cultures of white rat, mouse and hamster astrocytes. These
      cells were cultured on cover slides and infected with T. gondii tachyzoites or T.
      cruzi blood trypomastigotes. Results show that hamster astrocytes are more
      susceptible to the multiplication of both parasites than rat and mouse cells.
      There was no statistical difference between the T. gondii infection in rat and
      mouse astrocytes (p < 0.05), and this suggests an important role of other
      mechanisms or cells in the white rat natural resistance to this parasite. Because
      the hamster astrocytes are less resistant to these parasites multiplication and
      not necessarily to the invasion, any difference observed could be due to an
      intracellular effect: hamster brain astrocytes favor survival and multiplication
      of these parasites.

PMID- 15162772
TI  - Phytomedicinal potential of tropical cloudforest plants from Monteverde, Costa
      Rica.
AB  - A pharmacological survey of plants from Monteverde, Costa Rica, including 165
      species representing 61 families has been carried out. Crude plant extracts have
      been tested for in-vitro bactericidal and fungicidal activity as well as
      cytotoxic and anti-herpes activity. Of these, 123 extracts exhibited notable
      cytotoxicity, 62 showed antibacterial activity, 4 showed antifungal activity, and
      8 showed promising antiviral activity. Thus, 101 of the plant species examined in
      this work, or 62%, showed marked bioactivity in one or more bioassays. These
      results underscore the phytomedicinal potential of Neotropical cloud forests.

PMID- 15162773
TI  - [Sexual phase of the ferns Odontosoria schlechtendalii and Odontosoria scandens
      (Dennstaedtiaceae)].
AB  - The results of morphogenesis studies of the sexual phase of Odontosoria
      schlechtendalii and O. scandens are presented in this paper. In O.
      schlechtendalii and O. scandens the spores are triletes, non-chlorophyllous, and
      germinacion is of the Vittaria-type, devoid of perine, the exine is smooth and
      sometimes coarsely ridged to reticulate. The development pattern is of the
      Adiantum-type. The adult gametophyte is cordate-spathulate, with probable
      presence of anteridiogen in O. schlechtendalii, both species are glabrous. Sex
      organs are of the common type of the leptosporangiate ferns. The first leaves
      appeared after 56-92 days of culture, with petiole and plate divide narrow,
      trichomes bifurcate and stomate anomocytic.

PMID- 15162774
TI  - [In vitro establishment of Cryptomeria japonica (Taxocidaceae)].
AB  - In this work, it was achieved to establish in vitro shoots of Cryptomeria
      japonica from 20 year old trees. The shoots were disinfected and treated with six
      different concentrations of kinetin and belciladenine in order to induce their
      development and budding. It was evaluated the effect of quality and lighting
      intensity on these using for this orange light at 20 microEs-1 m-2 and white
      light at 30 microEs-1 m-2. For shoots rooting it was used different
      concentrations of NAA (naftalen acetic acid) and IBA (indolbutiric acid) alone or
      combined. BA and KIN induced the bud formation in Cryptomeria but it was observed
      the best budding with BA at 9.1 microM. White light and orange light promoved the
      growth of explants as well as the growth of new buds but it was higher with
      orange light. The bud rooting was observed but it was not possible to find the
      best auxin concentration for rooting because of the plentiful callus formation on
      the base of explants and the root formation was very sporadic. The rooted shoots
      were placed on a substrate for their acclimation in greenhouse conditions.

PMID- 15162775
TI  - Inter and intraspecific variation on reproductive phenology of the Brazilian
      Atlantic forest Rubiaceae: ecology and phylogenetic constraints.
AB  - The reproductive phenology of seven species of Rubiaceae from the Brazilian
      Atlantic rain forest was compared to evaluate the occurrence of phylogenetic
      constraints on flowering and fruiting phenologies. Since phenological patterns
      can be affected by phylogenetic constraints, we expected that reproductive
      phenology would be similar among plants within a family or genus, occurring
      during the same time (or season) of the year. Observations on flowering and
      fruiting phenology were carried out monthly, from December 1996 to January 1998,
      at Nucleo Picinguaba, Parque Estadual da Serra do Mar, Ubatuba, Sao Paulo State,
      Brazil. Nine phenological variables were calculated to characterize, quantify and
      compare the reproductive phenology of the Rubiaceae species. The flowering
      patterns were different among the seven species studied, and the Kruskal-Wallis
      test indicated significant differences in flowering duration first flowering,
      peak flowering and flowering synchrony. The peaks and patterns of fruiting
      intensity were different among the Rubiaceae species studied and they differed
      significantly from conspecifics in the phenological variables fruiting duration,
      fruiting peak date, and fruiting synchrony (Kruskal-Wallis test). Therefore, we
      found no evidence supporting the phylogenetic hypotheses, and climate does not
      seem to constrain flowering and fruiting patterns of the Rubiaceae species in the
      understory of the Atlantic forest.

PMID- 15162776
TI  - [Sexual compatibility between two types of Hylocerus (Cactaceae)].
AB  - There are two types of pitahaya that are cultivated in Yucatan Peninsula of
      Mexico. They differ mainly in the skin color of the fruit, one of them has a red
      skin (Uqroo1), while the other has a light yellow skin (Uqroo2) both belong to
      Hylocereus undatus (Haworth) Britt. & Rose. The yellow skin pitahaya is the
      sweetest. The studies were conducted using the methods of self pollination and
      cross pollination, with direct crosses and reciprocal pollination in order to
      evaluate the effect related to the quantity of fruits that accomplish their
      growing process. Some characteristic parameters of fruits, thus obtained, were
      used to detect the possible xenic effect. The control samples were collected from
      naturally pollinated flowers. The experimental design used was completely random
      and the experiment was repeated fifteen times. The results revealed that the
      Uqroo1 turned out to be self-compatible, and their fruits reached one hundred
      percent of development. On the other hand, Uqroo2 was self-incompatible, that is,
      it did not accept self pollen. The control samples of both types reached the same
      weight, and the fruits of the Uqroo2 produced by cross pollination had the same
      or more weight than the control samples. Several parameters were positively
      correlated. The coefficient between the number of seeds and the fruit weight was
      r = 0.84. The highest correlation that was found (r = 0.97) in the fruit weight
      and the pulp weight within both types. The fruits obtained by cross-pollination
      maintained the characteristic of the female progenitor. It is suggest intercalate
      the yellow pitahaya plants with another types or species of pitahaya, other than
      the Uqroo1.

PMID- 15162777
TI  - [Variation in fruit and seed size from 38 wild populations of Phaseolus lunatus
      (Fabaceae) from Central Valley, Costa Rica].
AB  - We studied the morfological diversity in fruits and seeds in 38 wild populations
      of Phaseolus lunatus var. lunatus (lima beans) in the central valley of Costa
      Rica. In order to do so, measured the length and width of the fruits and the
      length, width and thickness of seeds. We also calculated the ratio between these
      traits and determined the weight of 100 seeds. In general, we found significant
      variation between populations for all variables. When we grouped the 38
      populations into eight geographical regions within the study area, we found
      significant differences between regions. However, the levels of variation between
      populations within geographical regions was larger than that found between
      geographical regions. These findings suggested that there is no clear
      relationship between these variables and the geographical grouping established in
      this study. The implications of these findings for the establishment of
      strategies for in situ conservation of wild populations of lima beans are
      discussed.

PMID- 15162778
TI  - [Polymorphism of Phaseolus vulgaris var. aborigineus (fabaceae). Evidences of
      natural hibridation].
AB  - A polymorphic population of Phaseolus vulgaris var. aborigineus growing at the
      Northwest of Argentina was studied. In order to know the origin of this
      polymorphism, some plants belonging to the var. aborigineus, other plants showing
      floral dimorphism and other individuals with particular characters were
      collected. Their seeds, obtained after field-work treatments of autogamy and free
      pollination, were sown in a greenhouse, isolated of the access of pollinators.
      The growth of each plant was followed until its fructification, and the number of
      plants that died due to infections was recorded. The number of plants that
      flowered and fructified was registered in order to study their reproductive
      success. The floral, fruit and seed qualitative and quantitative characters were
      documented. With the results obtained, the authors concluded that those
      individuals that showed floral dimorphism are probably a result of hybridization
      and introgression between the var. aborigineus and "old cultivars". This
      hypothesis is supported by the presence of divergent segregation, observed in the
      offspring of the plants with this segregation. Other crops should allow the genic
      flow between the parental entities, with the consequence of the establishment of
      an hybrid population coexistent with their ancestors. Perhaps, as a result of
      introgression, the stabilized lines exhibit characters different from their
      parental varieties. The results of autopollination and free pollination in those
      individuals assigned to var. aborigineus, showed that free pollination brings a
      great genetic plasticity, because next generations can persist and resist
      infections. The offspring of the F1 was followed. The plants that belonged to
      var. aborigineus, product of free pollination, exhibited fast growth and were
      healthy, while the descendant of the individuals with the floral dimorphism
      showed characteristics that allowed to conclude the possible existence of
      degeneration of the hybrid progeny; this characteristics were: curled radicles
      with cotyledons that never emerge, plantule's apex that soon die with the
      following development of branches from the cotyledon's axil, and death after some
      weeks. This degeneration indicates that an unwanted gene flow in the area could
      lead to a decline in the wild bean population. The vigor, high reproductive
      success and resistance to illnesses of the individuals corresponding to the var.
      vulgaris, whose progenitor was treated for free fecundation, and the offspring of
      the plants with cultivated characteristics, are indicative of the necessity of
      preserving this germplasm to evaluate its agronomic potential to brief term. The
      DNA analyses already initiated, will allow the confirmation of the hypotheses
      outlined in this work.

PMID- 15162779
TI  - [The family Pontellidae (Crustacea: Copepoda) in la Ventosa Bay, Oaxaca, Mexico:
      systematies and basic ecology].
AB  - A study on ecological records of planktonic copepods from The Ventosa Bay,
      Oaxaca, Mexico is presented. Five species were identified: Labidocera acuta, L.
      lubbockii, Pontella agassizi, P. tenuiremis and Pontellina plumata. The most
      abundant species was L. acuta and their copepodite stages conforming the 95.7% of
      Pontellids, followed by L. lubbockii 4.09%; other species were less than one
      percent. The reproductive success of L. acuta is probably favored by its
      resistance to the changes in temperature and salinity, because of it is an
      eurytherme and euryhaline organism. Total density of this family was between 18
      and 472 copepods/100 m3 in 1987 and 1988. Nevertheless in 1992 and 1993 the
      density was between 490 to 123,030 copepods/100 m3. This copepod density
      increment could be related local phenomenon (upwelling) at the beginning and end
      of the year.

PMID- 15162780
TI  - [Lecithin essay in the diet of young Penaeus vannamei (Crustacea: Decapoda)].
AB  - The effect of different lecithin sources and presentations on growth, food
      conversion ratio and survival of P. vannamei (290 mg +/- 0.02) was studied. The
      bioassay was designed in order to compare different dietary levels and different
      quality of lecithin. Squid lecithin, crude soybean (7%), deoiled soybean lecithin
      (3.48%) in combination with fish oil or squid neutral lipids, in a partially
      dilapidate formula. The isoenergetic diets were fed ad libitum to four replicate
      groups (tanks) of 15 shrimps each (5 x 4 x 15), during 28 days. The result of the
      bioassay with the partially dilapidate formulas was; the best growth rate (191%)
      and FCR (1.69 +/- 0.041) were obtained with the diet containing 7% of soybean
      crude lecithin as the unique lipid source. Followed by the diet countering 3.94%
      deoiled lecithin and 2.42% Menhaden oil (172% and 2.03 +/- 0.054 respectively).
      As expected, the worst results were obtained without the dietary lecithin 121%
      and 2.42 +/- 0.129). Crude soybean lecithin alone covered the phospholipid and
      neutral lipids requirements as well as the combination of deoiled soybean
      lecithin with fish or squid oil.

PMID- 15162781
TI  - [Effect of the protein level in the diet on the development of young Australian
      lobsters, Cherax quadricarinatus (Decapoda: Parastacidae)].
AB  - An experimental study was conducted from October to December, 1999, in the
      aquaculture facilities of CIBNOR SC, at La Paz, BCS. To evaluate the effect of
      diet protein level on the productive response, in juveniles of the australian
      lobster, Cherax quadricarinatus, diets with four levels of crude protein (20.45,
      28.25, 37.33 y 45.44%), were formulated and probed. Growth, grow rate, survival,
      biomass and food conversion rate were greater in juveniles fed with diets of
      37.33 and 45.44% of crude protein. It is concluded that diet protein level
      affects the productive response of redclaw and a level of 37% of crude protein in
      the diet is enough to obtain acceptable results.

PMID- 15162782
TI  - [Effect of temperature on longevity and infection with the nematode
      Strelkovimermis spiculatus (Nemata: Mermithidae), a parasite of mosquitoes].
AB  - Strelkovimermis spiculatus is a common parasite of culicid species in Argentina.
      Effect of temperature on longevity and infectivity of juvenile preparasites of S.
      spiculatus was determined at 4, 10, 20 and 27 degrees C. Three containers with
      100 ml of dechlorinate water and 300 preparasites (12 hour-old), were placed for
      each day and temperature, during 40 days (total = 480 containers). Survived
      preparasites were counted on 12 containers per day (three for each temperature).
      When number of survived preparasites was determined, second instar larvae of
      Aedes aegypti were added to each container in a 10:1 ratio
      (preparasites:mosquito) to determine infectivity of daily survived preparasites.
      Longevity of preparasites decreased at higher temperatures. Maximum longevity of
      preparasites maintained at 4, 10, 20 and 27 degrees C were 35, 30, 25 and 27
      days, respectively. Survivorship of preparasites, exposed to the same
      temperatures, varied from 57% to 100% at day two, from 21% to 77% at day five and
      from 9% to 33% at day ten. Infectivity of preparasites maintained at temperatures
      from 4 to 27 degrees C was always higher than 70%. Extended longevity with
      maintenance of the infectivity capacity of preparasites, are important attributes
      to consider S. spiculatus an effective mean of controlling a large number of
      culicid species between 4 and 27 degrees C.

PMID- 15162783
TI  - Male and mosquito larvae survey at the Arenal-Tempisque irrigation project,
      Guanacaste, Costa Rica.
AB  - A monitoring of male and larvae of mosquitoes was conducted during 1991-1994, at
      the Irrigation Project in Arenal-Tempisque, Guanacaste, Costa Rica. CDC CO2
      baited traps were used to collect adults of mosquitoes and dips were used for
      immatures of culicids. A total of 1,480 larvae and 1,129 males of culicids were
      identified resulting in, Aedes with 6 species, Anopheles, Mansonia and Psorophora
      with 2 species, Culex with 21 species and Haemagogus, Limatus, Toxorhynchites and
      Uranotaenia with only one species each. The results indicate that, as occurred in
      other countries, irrigation projects must be under strict monitoring programs to
      prevent and control possible health problems in which mosquitoes act as vectors.

PMID- 15162784
TI  - Sexual behavior of mutant strains of the medfly Ceratitis capitata (Diptera:
      Tephritidae).
AB  - Males of the mutant strains (blind, vestigal-winged) of the Mediterranean fruit
      fly (medfly), Ceratits capitata (Wiedmann) showed differences in behavior
      compared with control (mass-reared) males. Mutant males made fewer mating
      attempts and achieved fewer matings than control males. Vestigal-winged females
      copulated less frequently with both mutants. Blind males climbed rather than
      jumped onto females and copulated in very low numbers compared with control and
      vestigal males. Blind females copulated normally with control, males and in very
      low numbers with both types of mutant males.

PMID- 15162785
TI  - The fish fauna in tropical rivers: the case of the Sorocaba River basin, Sao
      Paulo, Brazil.
AB  - A survey was carried out on the fish species in the Sorocaba River basin, the
      main tributary of the left margin of the Tiete River, located in the State of Sao
      Paulo, Brazil. The species were collected with gill nets. After identification of
      the specimens, their relative abundance, weight and standard length were
      determined. Up to the present moment there are not any studies that focus this
      subject in this hydrographic basin. Fifty-three species, distributed in eighteen
      families and six orders were collected. Characiformes were represented by twenty
      eight species, Siluriformes by seventeen species, the Gymnotiformes by three
      species, Perciformes and Cyprinodontiformes by two species, and the
      Synbranchiformes by one species. Among the collected species there were two
      exotic. The most abundant species were Astyanax fasciatus and Hypostomus
      ancistroides. In relation to total weight the most representative species were
      Hoplias malabaricus and Hypostomus ancistroides. Cyprinus carpio, Prochilodus
      lineatus, Schizodon nasutus and Hoplias malabaricus were the most representative
      species in relation to average weight. Largest standard length were recorded for
      Sternopygus macrurus, Steindachnerina insculpta, Eigenmannia aff. virescens and
      Cyprinus carpio.

PMID- 15162786
TI  - [The fish community in the Terminos lagoon: compared current structure].
AB  - The structure of the fish community in Terminos Lagoon, Campeche, is analyzed on
      the base the description of the abundance, distribution, length composition and
      identification of the dominant species. The results are discussed and compared
      with the published information. 437 trawl tows were made in 19 monthly collection
      in 23 sites between September 1997 to March 1999. A total of 25,588 individual
      with a total weight of 601.5 kg were grouped in 107 species, 76 gender and 37
      families. The abundance of the fish community showed the following intervals in
      temporal scale: 0.395 to 0.895 ind/m2; 8.637 to 18.316 g/m2 and 18.358 to 34.837
      g/ind. The Shannon index oscillated between 1.875 and 3.995 and 4.94 and 7.88
      respectively. 18 dominant species were identified. The most important species by
      its numerical abundance and appearance frequency is Arius melanopus that
      represents to the 26.5% of the total catch followed by Diapterus rhombeus with
      18.9%. As dominant species, Bairdiella chrysura, B. ronchus, Archosargus
      rhomboidalis, Eugerres plumieri, Cynoscion arenarius and Chaetodipterus faber,
      are fishing resources with local and regional value.

PMID- 15162787
TI  - Characteristics of Carcharhinus galapagensis from Salas y Gomez Island, Chile
      (Chondrichthyes: Carcharhinidae).

PMID- 15162788
TI  - A new species of hognose pitviper, genus Porthidium, from the southwestern
      Pacific of Costa Rica (Serpentes: Viperidae).
AB  - A new species of terrestrial pitviper, Porthidium porrasi, is described from
      mesophytic forests of the Peninsula de Osa and surrounding area of the Pacific
      versant of southwestern Costa Rica. It is most similar to P. nasutum and is
      characterized by a pattern of bands, persistence of the juvenile tail color in
      adults, and a high number of dorsal scales. Analysis of mtDNA sequences confirms
      its distinction from P. nasutum. The existence of this species reinforces the
      notion of elevated herpetofaunal endemism in southwestern Costa Rica.

PMID- 15162789
TI  - A new species of slender coralsnake from Colombia, and its clinal an ontogenetic
      variation (Serpentes, Elapidae: Leptomicrurus).
AB  - Leptomicrurus renjifoi is described from tropical semi-deciduous forest of the
      eastern Colombian Ilanos. It is one of the smallest species in the genus, is most
      similar to L. scutiventris, and it may be distinguished from known congeners by a
      combination of color, pattern, and scale characters. Evidence for the recognition
      of Leptomicrurus is convincing, although its members were recently thought to
      comprise a closely related assemblage within Micrurus. A supposedly aberrant
      specimen of L. scutiventris may indicate clinal or ontogenetic variation in
      pattern.

PMID- 15162790
TI  - Control measures implemented during the 2002 foot-and-mouth disease outbreak in
      the Republic of Korea.

PMID- 15162791
TI  - Clinical quiz. Sequelae of meningococcal sepsis.

PMID- 15162793
TI  - Why are the hydrocarbons in my chromatogram exhibiting peak tailing?

PMID- 15162792
TI  - A model for initial DNA lesion recognition by NER and MMR based on local
      conformational flexibility.
AB  - Initial recognition of DNA damage is the crucial but poorly understood first step
      in DNA repair by the human nucleotide excision repair(NER) and mismatch repair
      (MMR) systems. Failure by NER or MMR to recognize DNA damage threatens the
      genetic integrity of the organism and may play a role in carcinogenesis. Both NER
      and MMR recognize and repair a wide variety of structurally dissimilar lesions
      against the background of normal DNA. Previous studies have suggested that
      detection of thermodynamic destabilization of DNA caused by covalent damage and
      base mismatches is a potential mechanism by which repair pathways with broad
      specificity such as NER and MMR recognize their substrates. However, both NER and
      MMR respectively, repair a wide variety of stabilizing and destabilizing covalent
      DNA lesions and base pair mismatches. A common feature of lesions that are both
      thermodynamically stabilizing and destabilizing is the alteration of the local
      DNA flexibility (dynamics). In this review we describe the experimental evidence
      for altered dynamics from NMR and thermodynamic studies on normal and damaged DNA
      molecules with respect to recognition by NER and MMR. Based on these data, we
      propose a model for initial detection of lesions by both NER and MMR that occurs
      through an indirect readout mechanism of alternative DNA conformations induced by
      covalent damage and base mismatches.

PMID- 15162794
TI  - Why don't calibration curves always intersect the origin?

PMID- 15162795
TI  - Clinical quiz. Hereditary hemorrhagic telangiectasia.

PMID- 15162796
TI  - Role of eNOS in neovascularization: NO for endothelial progenitor cells.
AB  - Nitric oxide (NO) is a gaseous molecule with an astonishingly wide range of
      physiological and pathophysiological activities, including the regulation of
      vessel tone and angiogenesis in wound healing, inflammation, ischaemic
      cardiovascular diseases and malignant diseases. Recent data have revealed the
      predominant role of endothelial nitric oxide synthase (eNOS), an endothelial-cell
      specific isoform of NO producing enzyme, in both angiogenesis (the development of
      new blood vessels derived from existing vessels) and vasculogenesis (blood vessel
      formation de novo from progenitor cells). In addition, successes in gene therapy,
      together with the recent development of an eNOS-specific inhibitor, suggest that
      the modulation of eNOS might be a potent new strategy for the control of
      pathological neovascularization.

PMID- 15162797
TI  - von Hippel-Lindau tumor suppressor: not only HIF's executioner.
AB  - Loss of von Hippel-Lindau (VHL) protein function results in an autosomal-dominant
      cancer syndrome known as VHL disease, which manifests as angiomas of the retina,
      hemangioblastomas of the central nervous system, renal clear-cell carcinomas and
      pheochromocytomas. VHL tumor suppressor is a specific substrate-recognition
      component of the E3 ubiquitin complex, which regulates proteasomal degradation of
      the subunit of the hypoxia inducible transcription factor (HIF). Impaired VHL
      complex function leads to accumulation of HIF, overexpression of various HIF
      induced gene products and formation of highly vascular neoplasia. However, the
      ubiquitylating role of the VHL complex extends beyond its function in regulating
      HIF, as it appears to regulate the stability of other proteins that might be
      involved in various steps of oncogenic processes.

PMID- 15162798
TI  - [Relevance of the guidelines for the therapy of lateral humeral epicondylitis
      under the point of view of randomized controlled studies].

PMID- 15162799
TI  - Aneurysmal bone cyst arising from fibrous dysplasia of the frontal bone
      (2004:2b).

PMID- 15162800
TI  - An unusual hilar lesion (2004:5a).

PMID- 15162801
TI  - [Knee navigation and ligament balancing conditio sine equa non].

PMID- 15162802
TI  - [MRI or CT for the diagnosis of stenosis of the lumbar spinal canal? Results of a
      retrospective study].

PMID- 15162803
TI  - [Extracorporeal shock wave therapy and femur head necrosis--pressure measurements
      in the femur head].

PMID- 15162804
TI  - [Reduced opioid efficacy in chronic pain of support and locomotion systems].

PMID- 15162806
TI  - [UNISPACER -- a new minimally-invasive therapeutic concept for the isolated
      medial knee joint disease].

PMID- 15162805
TI  - [Primary bilateral knee replacement: is a less favorable postoperative
      rehabilitation phase to be expected?].

PMID- 15162808
TI  - Health care continuation coverage. Final rules.
AB  - This document contains final rules implementing the notice requirements of the
      health care continuation coverage (COBRA) provisions of part 6 of title I of the
      Employee Retirement Income Security Act of 1974 (ERISA or the Act). The
      continuation coverage provisions generally require group health plans to provide
      participants and beneficiaries who under certain circumstances would lose
      coverage (qualified beneficiaries) the opportunity to elect to continue coverage
      under the plan at group rates for a limited period of time. The final rules set
      minimum standards for the timing and content of the notices required under the
      continuation coverage provisions and establish standards for administering the
      notice process. These rules affect administrators of group health plans,
      participants and beneficiaries (including qualified beneficiaries) of group
      health plans, and the sponsors and fiduciaries of such plans. These rules also
      provide model notices for use by administrators of single-employer group health
      plans to satisfy their obligation to provide general notices and election
      notices.

PMID- 15162807
TI  - [The operative treatment of Spondyloptosis L5 / S1].

PMID- 15162809
TI  - [Hemovigilance and pediatrics. Self assessment questions].

PMID- 15162810
TI  - i.v.IG for autoimmune, fibrosis, and malignant conditions: our experience with
      200 patients.
AB  - Intravenous immunoglobin (i.v.IG) is generated from the plasma of more than
      10,000 healthy subjects. Originally i.v.IG was employed to supplement the missing
      Igs in subjects with immune-deficiencies. Later on it was given successfully to
      patients with autoimmune conditions, in some of which the benefits were confirmed
      by double blind studies (i.e.polymyositis), while in others remarkable case
      reports and series of patients have alluded to its beneficial effects. Especially
      when conventional therapies failed. Recently, due to multiple mechanisms, i.v.IG
      was found to be useful in reducing collagen deposition (i.e.scleroderma) and to
      prevent metastatic spread. When given properly (not more than 0.4 g/Kg. B.W. 5
      day), side effects are minimal. Yet, its high price (> 3000 US dollars per
      monthly course) precludes the application of i.v.IG more frequently.

PMID- 15162812
TI  - Do you know who your physician is? Placing physician information on the Internet.

PMID- 15162813
TI  - HIV-infected healthcare workers and practice modification.

PMID- 15162814
TI  - Sign on the dotted line: enforceability of signed agreements, upon divorce of the
      married couple, concerning the disposition of their frozen preembryos.

PMID- 15162815
TI  - Genetic discrimination, genetic privacy: rethinking employee protections for a
      brave new workplace.

PMID- 15162816
TI  - When things go wrong: the duty to disclose medical error.

PMID- 15162817
TI  - Adequate protection for the autonomous research subject? The disclosure of
      sources of funding and commercialisation in genetic research trials.

PMID- 15162818
TI  - First US-EU DNA repair meeting: endogenous stress, National Conference Center,
      VA, USA, 14-18 October 2003.

PMID- 15162819
TI  - Management of intraocular retinoblastoma and ocular prognosis.
AB  - Current management modalities for intraocular retinoblastoma, their indications,
      and ocular prognosis are reviewed. Enucleation, external beam radiotherapy,
      plaque radiotherapy, laser photocoagulation and hyperthermia, and cryotherapy are
      the modalities generally employed. Recently, neoadjuvant chemotherapy has been
      introduced for retinoblastoma to avoid external beam radiotherapy. New treatment
      modalities such as subconjunctival injection, selective ophthalmic artery
      injection, and vitreous injection are being investigated and have achieved
      favorable results. Although many modalities are employed, almost half of
      retinoblastoma eyes have to be enucleated. New treatment modalities are expected.

PMID- 15162820
TI  - Results of treatment of retinoblastoma that has infiltrated the optic nerve, is
      recurrent, or has metastasized outside the eyeball.
AB  - Since the development of chemotherapy regimens for patients with retinoblastoma
      started in the 1950s, various agents and regimens have been employed for various
      kinds of patients. Chemotherapy has been employed for: (1) patients with high
      risk features for metastases, such as patients with optic nerve involvement, (2)
      patients with orbital involvement, and (3) patients with distant metastasis.
      Effective systemic chemotherapeutic agents include vincristine, doxorubicin,
      cyclophosphamide, etoposide, cisplatin, and carboplatin, and, as well,
      intrathecal agents, including methotrexate, cytarabine, and corticosteroids are
      available. With the addition of appropriate chemotherapies to the conventional
      treatment modalities such as enucleation and radiotherapy, patients with advanced
      retinoblastoma are expected to obtain a survival benefit. Moreover, a new
      modality combined with autologous stem cell support allowed us to use high-dose
      alkylating agents such as thiotepa, melphalan, and cyclophosphamide, which
      resulted in better prognosis for patients with metastatic retinoblastoma. Because
      of the small number of patients with retinoblastoma and the diversity of the
      disease characteristics in individual patients, there have been no clinical
      trials to determine whether to recommend a particular regimen, or to identify
      specific criteria in patients who would benefit from chemotherapy. Well-designed
      prospective controlled trials are warranted to establish a standard treatment
      strategy for patients with extraocular retinoblastoma.

PMID- 15162821
TI  - Systemic chemotherapy as a new conservative treatment for intraocular
      retinoblastoma.
AB  - Retinoblastoma is the most common malignant intraocular tumor in childhood. With
      advances in the methods for early detection of this disease, the survival rate is
      over 90% in developed countries. The management of intraocular retinoblastoma has
      gradually changed over the past few decades. Every effort has been made to save
      life, with the preservation of the eye and sight, if possible. External beam
      radiotherapy has been a standard treatment for medium and large, or visually
      threatening, intraocular retinoblastoma, but it markedly increases the risk of
      cosmetic deformities and secondary cancer in children with germline RB mutations.
      For the past decade, primary systemic chemotherapy called "chemoreduction" has
      been employed to avoid radiotherapy and enucleation. This article gives an
      overview of the results of current trials of primary chemoreduction for
      intraocular retinoblastoma, and discusses its role and its limitations in
      conservative treatment. The article also discusses future directions to expand
      the indications for this treatment. Many children with advanced intraocular
      retinoblastoma could be spared external beam radiotherapy and enucleation, mostly
      as a result of chemoreduction and focal methods. Chemoreduction combined with
      focal treatments will continue to play an important role in the conservative
      management of children with intraocular retinoblastoma, possibly even in children
      with advanced disease, with the combined use of multidrug-resistance modulators.

PMID- 15162822
TI  - Outpatient clinic for genetic counseling and gene testing of retinoblastoma.
AB  - We report on the genetic counseling and gene testing of patients with
      retinoblastoma who visited the National Cancer Center Hospital, Tokyo, from April
      1997 through September 2003. During this period, 73 probands visited the clinic,
      and gene testing was performed in 51 individuals. Germline mutations of the RBI
      gene were detected in 20 individuals (39%); the frequencies were 82% (9/11) in
      bilateral/familial retinoblastoma, 50% (2/4) in unilateral/familial
      retinoblastoma, 50% (8/16) in bilateral/nonfamilial retinoblastoma, and 5% (1/20)
      in unilateral/nonfamilial retinoblastoma. Gene testing is indicated in the
      medical practice of hereditary retinoblastoma for familial risk assessment, while
      prior counseling is important for an understanding of the risks and benefits of
      gene testing. With improvements in patient prognosis, counseling for adult
      survivors is increasing in importance. Assessment of genetic risk to the
      offspring and prevention of secondary cancer are the primary issues of concern.
      Presymptomatic diagnosis of infants is effective for the proper assessment of the
      genetic risk and for making follow-up schedules for the detection of the tumor at
      an early stage.

PMID- 15162823
TI  - In vitro chemosensitivity assays of retinoblastoma cells.
AB  - The use of chemotherapy in treating retinoblastoma is presently increasing in
      importance. Because of the rarity of this disease, excellent in vitro
      chemosensitivity assays are necessary, not only for individualized testing but
      also for the development of chemotherapy regimens. It is instructive for
      improving such assays to discuss in vitro chemosensitivitly tests of tumor cells
      from clinical specimens according to a cell biological perspective. This review
      will first summarize and discuss the technical problems encountered with several
      representative in vitro chemosensitivity tests on clinical specimens, including
      retinoblastoma. The second part of this review will summarize the results of
      chemosensitivity tests on retinoblastoma specifically.

PMID- 15162824
TI  - Clinical trial of fundoscopy under general anesthesia for pediatric outpatients
      with retinoblastoma.
AB  - Retinoblastoma brings suffering, particularly to children. Formerly management
      during fundoscopy for children in Japan saw children's movements restricted with
      a blanket held by their parents or by nurses. This situation was sad, and the
      performance of the fundoscopy was limited because the children were crying and
      moving during the examination. After we received letters from the families of
      such children, we decided to introduce day-care general anesthesia for
      fundoscopy. After we investigated the current status of the treatment of
      retinoblastoma in leading countries, we carried out a trial of day-care general
      anesthesia for fundoscopy in 70 pediatric patients with retinoblastoma. We have
      now finished this first trial of day-care anesthesia, and we expect that
      discharge from hospital to places a longer distance away will be feasible.

PMID- 15162825
TI  - Impact of serum interleukin-18 level as a prognostic indicator in patients with
      epithelial ovarian carcinoma.
AB  - BACKGROUND: Interleukin-18 (IL-18), a cytokine produced by macrophages, is
      capable of inducing T-lymphocyte synthesis of interferon-gamma (IFN-gamma). In
      this study, for the first time, the serum concentration of IL-18 and its
      significance as a prognostic indicator was evaluated in patients with epithelial
      ovarian cancer. METHODS: The serum IL-18 level was measured by an enzyme-linked
      immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8
      healthy controls. Relationships between the IL-18 level and clinicopathological
      features were examined by univariate and multivariate analyses. RESULTS: The
      median serum IL-18 level in the ovarian cancer patients was 229.6 pg/ml, and the
      level was significantly elevated compared with that in the normal controls (151.3
      pg/ml; P < 0.01). No significant correlations were detected between the IL-18
      level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate
      analysis, overall survival was shown to be affected by IL-18 serum levels.
      However, multivariate analysis failed to demonstrate an independent prognostic
      significance for IL-18 serum levels, while confirming the role of previously
      established prognostic variables, such as performance status, stage, and residual
      tumor. CONCLUSION: This study showed that IL-18 serum levels were elevated in
      ovarian cancer patients and were correlated with overall survival, although they
      were shown not to be an independent prognostic factor.

PMID- 15162826
TI  - Clinical outcome of transrectal ultrasound-guided prostate biopsy, targeting
      eight cores, for detecting prostate cancer in Japanese men.
AB  - BACKGROUND: The objective of this study was to evaluate the clinical usefulness
      of transrectal ultrasound (TRUS)-guided eight-core prostate biopsy for detecting
      prostate cancer in Japanese men. METHODS: Between January 1998 and September
      2002, a total of 628 consecutive patients underwent TRUS-guided biopsy of the
      prostate. As a rule, eight cores were taken from each patient; that is, standard
      sextant cores from the peripheral zone and two additional cores from the
      bilateral anterior lateral horns (ALHs). The present study included 428 patients
      who underwent an initial biopsy, whose age was between 50 and 79 years, and whose
      prostate-specific antigen (PSA) value was less than 20.0 ng/ml. The cancer
      detection rate was calculated according to age, PSA, digital rectal examination
      (DRE) and TRUS findings, prostate volume, and PSA density (PSAD). We also
      assessed whether the sampling of the two extra cores from the ALHs increased the
      cancer detection rate. RESULTS: Of the 428 patients, 101 (23.6%) were diagnosed
      as having cancer by eight-core prostate biopsies. The cancer detection rate was
      significantly associated with the PSA value (ng/ml; < or =4 versus 4-10, versus
      10-20), DRE findings (normal versus abnormal), TRUS findings (normal versus
      abnormal), and PSAD (ng/ml2; < or =0.15 versus >0.15). but not with age (years: <
      or =70 versus >70) on prostate volume (ml; < or =30 versus 30-50, versus >50). Of
      the 101 patients diagnosed as having prostate cancer, 11 had positive cores only
      in the ALH; that is, the increase in the cancer detection rate yielded by
      obtaining two extra cores from the ALHs was 10.9%. CONCLUSION: Despite the
      reasonable strategy, systematic prostate biopsy targeting eight cores did not
      significantly improve the cancer detection rate compared with that of standard
      sextant biopsy in Japanese men. However, the increased cancer detection rate
      yielded by additional sampling from the ALHs was comparatively prominent in the
      subgroup whose PSA value was in the gray zone (4-10 ng/ml) or whose prostate
      volume was greater than 50 ml.

PMID- 15162827
TI  - Comparative evaluation of 201Tl SPECT and CT in the follow-up of irradiated brain
      tumors.
AB  - BACKGROUND: Radiation-induced changes in post-irradiated brain tumors may produce
      morphological alterations similar to those of tumor recurrence on computed
      tomography (CT). However, 201Tl single-photon-emission computed tomography
      (SPECT), with its ability to image metabolic changes, may differentiate post
      irradiated gliotic changes from metabolically active congregations of viable
      tumor cells. This study was carried out to compare these two imaging modalities
      for the follow-up evaluation of post-irradiated brain tumors. METHODS: Thirty
      five patients with previously irradiated primary brain tumors were evaluated for
      this study. 201Tl SPECT and CT were carried out during follow-up, which ranged
      from 3 to 125 months (median, 18 months). These findings were compared with the
      clinical outcome, as observed during the subsequent follow-up. RESULTS:
      Sensitivity, specificity, and the overall accuracy of 201Tl SPECT were 82.7%,
      83.3%, and 82.8%, compared to 58.6%, 66.6%, and 58.3%, respectively, for CT. Post
      scan progression-free survival (PFS) was significantly different for those
      patients having positive and those having negative evidence of tumor recurrence
      based on the imaging studies during follow-up. However, PFS was better correlated
      with 201Tl SPECT results than with the CT results. With 201Tl SPECT, median PFS
      was 4 months for those with positive reports, versus 33 months for those with
      negative reports (P = 0.003), compared to a corresponding median PFS of 3 months
      versus 14 months (P = 0.025), respectively, with CT. On multivariate analysis,
      age and 201Tl SPECT were the only significant variables for predicting post-scan
      PFS. CONCLUSION: 201Tl SPECT, with its ability to be taken up by viable tumor
      tissues, is superior to CT for the follow-up evaluation of post-irradiated brain
      tumors.

PMID- 15162828
TI  - A pilot study of neoadjuvant chemotherapy with mitomycin C, etoposide, cisplatin,
      and epirubicin for adenocarcinoma of the cervix.
AB  - BACKGROUND: To evaluate the efficacy and toxicity of the combination of mitomycin
      C, etoposide, cisplatin, and epirubicin (MEPA) as neoadjuvant therapy for
      patients with cervical adenocarcinoma. METHODS: Fourteen patients with cervical
      adenocarcinoma received neoadjuvant MEPA therapy followed by radical
      hysterectomy. The International Federation of Gynecology and Obstetrics stage
      was: IB1 in 2 patients, IB2 in 5, and IIB in 7. The MEPA regimen consisted of
      mitomycin C (15 mg/m2) on day 1, etoposide (70 mg/m2) on days 1 to 3, cisplatin
      (15 mg/m2) on days 1 to 5, and epirubicin (30 mg/m2) on day 1, with this course
      being repeated every 4 weeks. After two or three courses of chemotherapy, all
      patients underwent radical hysterectomy. Postoperative radiotherapy was given to
      6 patients who showed risk factors at surgery. RESULTS: Of the 14 patients, 7 had
      complete remission (CR) clinically, 6 had partial remission, and only 1 showed no
      change. Examination of surgical material revealed no residual disease in 6
      patients, and microscopic residual disease (<5 mm) in 2 patients. The patients
      who had no residual disease or microscopic disease in their hysterectomy
      specimens showed a significantly longer survival than those with macroscopic
      residual disease (P = 0.012). The dose-limiting toxicity was myelosuppression. Of
      the 33 treatment cycles administered, leukopenia of grade 3 or more occurred in
      70%,and thrombocytopenia of grade 3 or more occurred in 79%. There were no
      therapy-related deaths. CONCLUSION: Although severe myelosuppression was also
      observed, there was a satisfactory response rate to MEPA therapy, which showed a
      good pathological CR rate.

PMID- 15162829
TI  - Limited usefulness of the free-to-total prostate-specific antigen ratio for the
      diagnosis and staging of prostate cancer in Japanese men.
AB  - BACKGROUND: The objective of this study was to evaluate the clinical significance
      of measuring the free-to-total (f/t) prostate-specific antigen (PSA) ratio for
      the differentiation of prostate cancer from benign prostatic hypertrophy (BPH)
      and for the staging of prostate cancer in Japanese men. METHODS: Before
      treatment, tPSA and fPSA were measured in 147 patients with prostate cancer and
      in 253 with BPH, using immunofluorometric techniques. Furthermore, the f/t PSA
      ratio and the tPSA density of the whole prostate (PSAD) were calculated. RESULTS:
      The tPSA and PSAD levels in patients with prostate cancer paralleled the clinical
      stage, and were significantly higher than the levels in patients with BPH, while
      the f/t PSA ratio was not associated with clinical stage, despite the
      significantly lower values in prostate cancer patients than in BPH patients.
      Furthermore, the tPSA and PSAD values, but not the f/t PSA ratio, were
      significantly different between patients with pathologically extraprostatic
      disease and those with organ-confined disease. Calculation of the specificity of
      each assay within the range of 80%-95% sensitivity showed that tPSA and PSAD
      provided better specificities than the f/t PSA ratio. However, there was no
      significant difference in specificities among these three assays. In prostate
      cancer and BPH patients with PSA values of 4.1-10 ng/ml, the specificities of
      tPSA and PSAD were also superior to that of the f/t PSA ratio. CONCLUSION: These
      findings suggest that measurement of the f/t PSA ratio does not provide any
      significant additional information for the diagnosis and staging of prostate
      cancer in Japanese men when tPSA and PSAD values are available.

PMID- 15162830
TI  - Transcutaneous IL-2 uptake mediated by Transfersomes depends on concentration and
      fractionated application.
AB  - INTRODUCTION: Transfersomes (TF) are new, ultradeformable carriers with
      characteristics that enable them to penetrate the skin spontaneously. TFs are
      able to transport noninvasively both low- and high-molecular-weight molecules
      into the body. MATERIALS AND METHODS: TFs contain phosphatidylcholine and sodium
      cholate. Recombinant human interleukin-2 (Proleukin, Chiron) was added to the TFs
      and incubated for 24 h at 4 degrees C. The immunotransfersomes (ITF) were
      isolated from free interleukin-2 (IL-2) by filtration (Centrisart, Sartorius).
      Twenty-five thousand, 50,000 and 150,000 IU pure IL-2 and ITFs, which had been
      incubated with the same concentrations of IL-2, were applied subcutaneously
      (s.c.) (n = 8) and epicutaneously (e.c.) (n = 8) to mice. The IL-2 serum
      concentrations in the mice were then measured by ELISA after 2, 4, 6, 8, 10 and
      24 h. Fractionation of the transdermal IL-2 application was also examined as a
      means of improving uptake. RESULTS: In concentrations of 25,000 and 50,000 IU IL
      2, the subcutaneous application of ITFs resulted in a longer lasting IL-2 serum
      concentration than did the subcutaneous application of pure IL-2. While at 25,000
      IU, the epicutaneous application of ITFs resulted in serum concentrations
      comparable to those resulting from s.c. application, at 50,000 and 150,000 IU,
      only 50% and 22.6% of the maximum serum concentration resulting from the s.c.
      application of pure IL-2 was obtained. Fractionating the transdermal IL-2
      application improved uptake. CONCLUSION: We were able to show that biologically
      active IL-2 can be bonded to TFs up to 75%. It is possible to transport IL-2
      through the skin using TFs. Both the concentration-dependent saturation of the
      TFs with IL-2 and fractionation of the application resulted in differing degrees
      of transcutaneous IL-2 uptake.

PMID- 15162831
TI  - Endogenous production of TNFalpha is a potent trigger of NFkappaB activation by
      irradiation in human monocytic cells THP-1.
AB  - Irradiation causes DNA damage and induces neoplastic transformation. In response
      to irradiation, cells induce genes or activate proteins that protect themselves
      from the external insult. Nuclear factor kappaB (NFkappaB) activates
      transcription of target genes and plays important roles in inflammation. We
      studied the mechanism(s) for activation of NFkappaB by irradiation in human
      monocytic cells THP-1. Gel mobility shift assays showed that irradiation
      stimulated the NFkappaB-DNA binding activity of nuclear extracts from these
      cells. Western blot analysis using polyclonal antibody against phosphorylated
      IkappaB protein showed that irradiation increased the levels of phosphorylated
      IkappaB. The production of tumor necrosis factor alpha (TNFalpha) was stimulated
      by irradiation in these cells. Treatment with exogenously added TNFalpha also
      stimulated the NFkappaB binding activity with concomitant degradation of IkappaB.
      Further study found that the activation of NFkappaB by irradiation was inhibited
      by a neutralizing anti-TNFalpha antibody. Macrophages from TNFalpha-deficient
      mice were also defective in the irradiation-induced activation of NFkappaB. These
      results indicate that endogenous production of TNFalpha in macrophages/monocytes
      is required for NFkappaB activation by irradiation. Our data also suggest that
      TNFalpha in monocytes/macrophages exposed to irradiation is involved in signal
      transduction network initiation.

PMID- 15162832
TI  - Differential effects of LPS and TGF-beta on the production of IL-6 and IL-12 by
      Langerhans cells, splenic dendritic cells, and macrophages.
AB  - We examined modulatory effects of lipopolysaccharide (LPS) on IL-6 and IL-12
      production by mouse Langerhans cells (LC), spleen-derived CD11c+ dendritic cells
      (DC), and macrophages (Mphi). Low dose LPS (1 ng/ml) increased IL-6 and IL-12 p40
      production by Mphi. LPS slightly augmented IL-6 production but showed no effect
      on IL-12 p40 production by DC. In contrast, only high dose LPS (1 microg/ml)
      induced IL-6 but not IL-12 p40 production by LC. CD14 expression was the highest
      on Mphi and then on DC, but not on LC, which may explain the difference in
      responsiveness to LPS. We also found that TGF-beta inhibited IL-6 and IL-12 p40
      production by LPS-stimulated Mphi. However, TGF-beta did not inhibit IL-6
      production and even enhanced IL-12 p40 production by anti-CD40/IFN-gamma
      stimulated Mphi. Concerning LC, TGF-beta enhanced IL-6 and IL-12 p40 production
      when stimulated with anti-CD40/IFN-gamma alone or with anti-CD40/IFN-gamma and
      LPS. Taken together, these findings indicate diverse effects of LPS and TGF-beta
      on these antigen presenting cells, which probably represents their differential
      roles in the innate immunity.

PMID- 15162834
TI  - Interleukin-18 enhances the production of interferon-gamma (IFN-gamma) by
      allergen-specific and unspecific stimulated cord blood mononuclear cells.
AB  - BACKGROUND: IL-18 is a pleiotropic cytokine involved in the polarisation of T
      cell response. This study was performed to determine whether or not IL-18 is
      detectable in phytohemagglutinin (PHA) or betalactoglobulin (BLG) stimulated
      supernatants of cord blood mononuclear cells (CBMC) and to study the in vitro
      effect of IL-18 on the interferon (IFN)-gaamma and IL-13 release of CBMC of
      healthy neonates. METHODS: CBMC of neonates were isolated by Ficoll density
      centrifugation. The cytokines IFN-gamma, IL-13 and IL-18 in the cell culture
      supernatants were measured using the ELISA technique following stimulation with a
      unspecific (PHA 20 microg/ml) and an allergen-specific stimulus (BLG 25
      microg/ml). In order to study the in vitro effect of IL-18, CBMC were stimulated
      either with medium alone or with IL-18, IL-18 + PHA and IL-18 + BLG. RESULTS: IL
      18 levels in supernatants of CBMC were low and did not vary significantly between
      unstimulated and PHA or BLG stimulated cell cultures (median 21.4; 23.5 and 15.5
      pg/ml, respectively). IFN-gamma and IL-13 levels were significantly higher in
      response to PHA and BLG (PHA: IFN-gamma, 6154; IL-13, 4357; BLG: IFN-gamma, 801;
      IL-13, 249 pg/ml) compared to unstimulated cell cultures. The addition of IL-18
      to PHA or BLG stimulated CBMC significantly enhanced the IFN-gamma release (PHA:
      6154; PHA + IL-18: 13474, p = 0.0001; BLG: 801; BLG + IL-18: 1077, p = 0.008). In
      comparison to incubation without IL-18, the release of IL-13 was invariable or
      even reduced, when CBMC were stimulated with PHA + IL-18 (4026, p = 0.16) or BLG
      + IL-18 (124, p = 0.0001) compared to stimulation of CBMC with PHA (4357 pg/ml)
      or BLG (249 pg/ml) alone. CONCLUSIONS: IL-18 is detectable in supernatants of
      CBMC. We observed a significant effect of IL-18 + PHA as well as IL-18 + BLG on
      IFN-gamma release in vitro. Based on our findings we conclude that IL-18 could
      act as a strong TH1-inducing factor on stimulated CBMC also in vivo.

PMID- 15162833
TI  - In vitro analyses of tissue structure and interleukin-1beta expression and
      production by human oral mucosa in response to Candida albicans infections.
AB  - Clinical and experimental observations suggest that oral epithelial cells play a
      key role in host defenses against candidal infections through cytokines and
      chemokines. We thus attempted to determine whether oral epithelial cells convey
      IL-1beta as a pro-inflammatory cytokine in response to Candida albicans
      infections. We created engineered human oral mucosa (EHOM), put them in contact
      with live and heat-inactivated C. albicans (10(5) yeast/cm2), and measured the
      expression of IL-1beta mRNA and protein. Tissue structure and C. albicans
      morphology were also evaluated. Only live C. albicans modulated IL-1beta
      expression and secretion. IL-1beta mRNA expression significantly increased during
      the early stages of infection and decreased during the later stages. The
      modulatory effect of C. albicans on IL-1beta expression was confirmed by the fact
      that increased amounts of inactive IL-1beta (33 kDa) were detected early during
      the infection which then dropped dramatically. There was a significant and time
      dependent increase in the amount of the active form of IL-1beta (17 kDa) secreted
      into the supernatant by epithelial cells infected with live C. albicans.
      Histological features revealed damage to infected tissues (separation of
      epithelial cells, edema, vacuolization, reduction in thickness) compared to
      uninfected ones. Morphological analyses showed that C. albicans changed from a
      blastospore to a hyphal form at later infection periods. This transformation was
      very pronounced at 8 and 24 h post-infection. These results provide additional
      evidence for the contribution of oral epithelial cells to local defenses against
      exogenous stimulations such as C. albicans infections.

PMID- 15162835
TI  - Madimadi, Korean folk medicine, blocks TNF-alpha, IL-1beta, and IL-8 production
      by activated human immune cells.
AB  - Madimadi, a Korean folk medicine, has been applied to treat rheumatoid arthritis
      (RA). However, its mechanisms of action have not been examined. The involvement
      of inflammatory cytokines, particularly TNF-alpha, IL-1beta, and IL-8, resulting
      in local inflammation in the pathogenesis of RA is now widely accepted. Madimadi
      dose-dependently inhibited TNF-alpha, IL-1beta, and IL-8 production from
      activated human mast cells (HMC-1). RT-PCR revealed inhibition of TNF-alpha and
      IL-1beta transcription in activated HMC-1. In addition, we confirmed potent
      inhibition of TNF-alpha and IL-1beta production by Madimadi using purified human
      blood PBMC from an active RA group, but not from healthy or disease control
      groups. These novel insights into the immunosuppressive action of Madimadi are
      likely to impact the clinical use of this agent.

PMID- 15162836
TI  - Safety assessment of dichlorophene and chlorophene.
AB  - Dichlorophene is a halogenated phenolic compound that functions as a bacteriocide
      and fungicide in cosmetics. Chlorophene is a halogenated phenolic compound that
      functions as a biocide and preservative in cosmetics. Dichlorophene was reported
      to be used in a total of five cosmetic formulations at concentrations of 0% to
      1.0%, but Chlorophene was not reported to be used. Dichlorophene is prohibited
      for use in cosmetic ingredients in Japan. In Europe, the maximum authorized
      concentration allowed for Dichlorophene is 0.5% and for Chlorophene is 0.2%. The
      major impurity of Dichlorophene is the trimer 4-chloro-2,6-bis(5-chloro-2
      hydroxybenzyl)phenol. In rats, Dichlorophene sulfate, Dichlorophene
      monoglucuronide, and Dichlorophene diglucuronide were the major metabolites of
      Dichlorophene and were excreted, mainly in the urine. The glucuronic acid
      conjugate, the sulfate ester conjugate, and two minor metabolites of Chlorophene
      were the metabolites found in rat urine. Chlorophene was incompletely absorbed
      through the rat skin. These chemicals exhibited low toxicity in acute oral
      toxicity studies in several animal species. Some evidence of toxicity with both
      chemicals was found in short-term oral toxicity studies in mice and rats;
      nephropathy was the principal finding. Chronic toxicity data were not available
      for Dichlorophene. Rats and mice dosed with Chlorophene for 2 years had a dose
      related and sex-related increase in the severity of nephropathy. In animal tests,
      Dichlorophene and Chlorophene were ocular irritants. No inhalation toxicity data
      were available for these ingredients. Dichlorophene up to 10% concentration
      resulted in no to minimal irritation when applied to the intact and abraded skin
      of rabbits. Chlorophene was severely irritating to rabbits in most dermal
      irritation studies. Studies on guinea pigs gave positive and negative results in
      sensitization tests of Dichlorophene. A dose-related contact hypersensitivity
      response to Chlorophene was reported in mice. No reproductive or developmental
      toxicity data were available for Dichlorophene, but there was some evidence of
      non-dose-dependent developmental toxicity with Chlorophene in rabbits.
      Dichlorophene was positive in the Ames mutagenicity assay, but not in mammalian
      or fruit fly test systems. Chlorophene was mutagenic in four in vitro mammalian
      test systems. Carcinogenicity studies for Dichlorophene were not found. Neoplasms
      were not observed in rats treated with Chlorophene for 2 years; however a
      significant incidence of neoplasms was observed in mice so treated. A 1-year
      National Toxicology Program (NTP) study concluded that Chlorophene was a
      cutaneous irritant and a weak skin tumor promoter but had no activity as an
      initiator or complete carcinogen. Dichlorophene was not a sensitizer in clinical
      dermal sensitization tests. Some reactions to Chlorophene occurred in some, but
      not all, clinical dermal sensitization tests. Positive photopatch tests to
      Dichlorophene were found in 13/469 patients. Although these ingredients were
      ocular irritants at high concentrations, the risk at concentrations which are
      actually used in cosmetic formulations was uncertain. Overall, the available data
      were insufficient to support safety of Dichlorophene or Chlorophene. Additional
      data needed include (1) method of manufacture and impurities data (especially the
      trimer in Dichlorophene); (2) photosensitization and photocarcinogenicity data
      for Dichlorophene; (3) dermal reproductive and developmental toxicity data for
      Dichlorophene (as a function of dose); and (4) ocular irritation at concentration
      of use, if available.

PMID- 15162837
TI  - Safety assessment of MIBK (methyl isobutyl ketone).
AB  - MIBK (Methyl Isobutyl Ketone) is an aliphatic ketone that functions as both a
      denaturant and solvent in cosmetic products. Current use in cosmetic products is
      very limited, but MIBK is reported to be used in one nail correction pen (volume
      = 3 ml) at a concentration of 21%. The maximum percutaneous absorption rate in
      guinea pigs is 1.1 micromol/min/cm2 at 10 to 45 min. Metabolites include 4
      hydroxy-4-methyl-2-pentanone (oxidation product) and 4-methyl-2-pentanol (4-MPOL)
      (reduction product). Values for the serum half-life and total clearance time of
      MIBK in animals were 66 min and 6 h, respectively. In clinical tests, most of the
      absorbed MIBK had been eliminated from the body 90 min post exposure. MIBK was
      not toxic via the oral or dermal route of exposure in acute, short-term, or
      subchronic animal studies, except that nephrotoxicity was observed in rats dosed
      with 1 g/kg in a short-term study. MIBK was an ocular and skin irritant in animal
      tests. Ocular irritation was noted in 12 volunteers exposed to 200 ppm MIBK for
      15 min in a clinical test. A depression of the vestibulo-oculomotor reflex was
      seen with intravenous infusion of MIBK (in an emulsion) at 30 microM/kg/min in
      female rats. The no-observed-effect level in rats exposed orally to MIBK was 50
      mg/kg. Both gross and microscopic evidence of lung damage were reported in acute
      inhalation toxicity studies in animals. Short-term and subchronic inhalation
      exposures (as low as 100 ppm) produced effects in the kidney and liver that were
      species and sex dependent. Dermal doses of 300 or 600 mg/kg for 4 months in rats
      produced reduced mitotic activity in hair follicles, increased thickness of horny
      and granular cell layers of the epidermis, a decrease in the number of reactive
      centers in follicles (spleen), an increase in the number of iron-containing
      pigments in the area of the red pulp (spleen), and a reduction in the lipid
      content of the cortical layer of the adrenal glands. Neuropathological changes in
      the most distal portions of the tibial and ulnar nerves were observed in young
      adult rats which inhaled 1500 ppm MIBK for up to 5 months. No adverse effects
      were seen in any other neurological end point by any route of exposure in other
      studies using rats or other animal species. Clinical tests demonstrated a
      threshold for MIBK-induced irritation of the lungs at 0.03 to 0.1 mg/L after 1
      min of respiration. MIBK was not mutagenic in the Ames test or in a mitotic gene
      conversion assay in bacteria. Mammalian mutagenicity test results were also
      negative in the following assays: mouse lymphoma, unscheduled DNA synthesis,
      micronucleus, cell transformation, and chromosome damage. MIBK did not induce any
      treatment-related increases in embryotoxicity or fetal malformations in pregnant
      Fischer 344 rats or CD-1 mice that inhaled MIBK at concentrations of 300, 1000,
      or 3000 ppm. There was evidence of treatment-related maternal toxicity only at
      the highest concentration tested. MIBK applied to the tail of rats daily at doses
      of 300 or 600 mg/kg for 4 months produced changes in the testes, including a
      reduction in the number of spermatocytes, spermatids, and spermatozoa. An ongoing
      carcinogenicity study of MIBK being conducted by the National Toxicology Program
      will be considered when the results are available. On the basis of the
      information that is currently available, MIBK is considered safe as used in nail
      polish removers and as an alcohol denaturant in cosmetic products.

PMID- 15162838
TI  - Final report on the safety assessment of octoxynol-1, octoxynol-3, octoxynol-5,
      octoxynol-6, octoxynol-7, octoxynol-8, octoxynol-9, octoxynol-10, octoxynol-11,
      octoxynol-12, octoxynol-13, octoxynol-16, octoxynol-20, octoxynol-25, octoxynol
      30, octoxynol-33, octoxynol-40, octoxynol-70, octoxynol-9 carboxylic acid,
      octoxynol-20 carboxylic acid, potassium octoxynol-12 phosphate, sodium octoxynol
      2 ethane sulfonate, sodium octoxynol-2 sulfate, sodium octoxynol-6 sulfate, and
      sodium octoxynol-9 sulfate.
AB  - Octoxynols are ethoxylated alkylphenols in which the size of the molecule is
      related to the number of moles of ethylene oxide used in synthesis. Reactions are
      performed at elevated temperature, under pressure, and in the presence of NaOH.
      It is possible that the synthesis may leave trace amounts of ethylene oxide, 1,4
      dioxane, and unreacted C9 phenols. Octoxynols of various chain lengths as well as
      octoxynol salts and organic acids function in cosmetics either as surfactants-
      emulsifying agents, surfactants--cleansing agents, surfactant--solubilizing
      agents, or surfactants--hydrotropes in a wide variety of cosmetic products at
      concentrations ranging from 0.0008% to 25%, with most less than 5.0%. The
      octoxynols are chemically similar to nonoxynols, the safety of which were
      previously considered. Long-chain nonoxynols (9 and above) were considered safe
      as used, whereas short-chain nonoxynols (8 and below) were considered safe as
      used in rinse-off products and safe at concentrations less than 5% in leave-on
      formulations. Acute exposure of hamsters to Octoxynol-9 by bronchopulmonary
      lavage produced pneumonia, pulmonary edema, and intra-alveolar hemorrhage.
      Octoxynol-9 at doses over 1 g/kg was toxic in rats and in mice in acute oral
      toxicity studies. No significant effects were noted in short-term oral studies of
      Octoxynol-9 in rats, in subchronic oral studies of Octoxynol-40 in rats and dogs,
      or in chronic oral studies of Octoxynol-40 in rats. The intraperitoneal LD50 of
      Octoxynol-9 in rats and mice was around 100 mg/kg. In skin irritation studies,
      octoxynols ranged from nonirritating to moderately irritating. Octoxynols were
      not ocular irritants in one rabbit study, but in others there was ocular
      irritation. No immune system toxicity in CF-1 female mice was noted following the
      intraperitoneal injection of Octoxynol-9 followed by subcutaneous immunization
      with sheep red blood cells (SRBCs). Octoxynol-9 produced no humoral and cell
      mediated immune responses, or autoimmune response in mice. In the Ames test,
      Octoxynol-1 was not mutagenic with and without metabolic activation nor was
      Octoxynol-9 clastogenic. Results for Octoxynol-9 were negative in the following
      assays: unscheduled DNA synthesis, hypoxanthine guanine phosphoribosyl
      transferase mutation assay, malignant transformation assay, DNA alkaline
      unwinding test, and mouse lymphoma thymidine kinase locus forward mutation assay.
      Ethoxylated alkylphenols are generally considered to be estrogenic in that they
      mimic the effects of estradiol. Dermal exposure at three dose levels of rats to
      Octoxynol-9 failed to induce any malformations by category (external, visceral,
      or skeletal) or by individual anatomical location that were different from
      controls at statistically significant level. An increased incidence of a
      vestigial thoracic rib was observed in all dose groups. Octoxynol-9 also did not
      induce developmental toxicity (number of viable litters, liveborn per litter,
      percentage survival, birth weight per pup, and weight gain per pup) in female
      specific pathogen-free CD-1 mice dosed daily by gavage on gestation days 6
      through 13. No reproductive toxicity was seen in male albino rats which received
      5% Octoxynol-40 in the diet daily for 3 months; however, in an in vitro test,
      Octoxynol-9 (0.24 mg/ml) totally immobilized all human spermatozoa within 20 s.
      Women who used Nonoxynol-9 or Octoxynol-9 as spermicides, but who did become
      pregnant, did not have an increase in the overall risk of fetal malformations. In
      a human skin irritation study, formulations containing 2.0% Octoxynol-9 were
      classified as moderately irritating and minimally irritating, respectively, in a
      24-h single-insult, occlusive patch test. Octoxynol-9 (1.0%) was classified as a
      nonirritant in a clinical study of nine subjects patch tested for 4 consecutive
      days. The skin sensitization potential of Octoxynols-1, -3, -5, -9, and -13 was
      evaluated using 50 subjects. Octoxynol-1 induced sensitization in two subjects;
      all other results were negative. No sensitization was observed in the following
      studies: 8.0% Octoxynol-9 in 103 subjects, 0.5% Octoxynol-9 in 102 subjects, and
      0.1% Octoxynol-9 in 206 subjects. Concerns about even trace levels of 1,4
      dioxane, ethylene oxide, or unreacted C9 led to the recommendation that levels be
      limited. Concerns about the ocular irritancy of short-chain octoxynols led to a
      recommendation that they should not be used in products that will be used in the
      area surrounding the eyes. A limitation on the use concentration for short-chain
      octoxynols (8 and below) arose from consideration of the skin sensitization
      potential of octoxynols and the recognition that the short-chain octoxynols could
      be absorbed into the skin more than the long-chain octoxynols. Overall, based on
      the available data, it was concluded that long-chain octoxynols (9 and above) are
      safe as used, whereas short-chain octoxynols (8 and below) are safe as used in
      rinse-off products and safe at concentrations less than 5% in leave-on
      formulations.

PMID- 15162839
TI  - American College of Toxicology: policy statement on the use of animals in
      toxicology.

PMID- 15162840
TI  - Biography of Professor Jan Roubal, MD, PhD.

PMID- 15162841
TI  - Risk from inhaled mycotoxins in indoor office and residential environments.
AB  - Mycotoxins are known to produce veterinary and human diseases when consumed with
      contaminated foods. Mycotoxins have also been proposed to cause adverse human
      health effects after inhalation exposure to mold in indoor residential, school,
      and office environments. Epidemiologic evidence has been inadequate to establish
      a causal relationship between indoor mold and nonallergic, toxigenic health
      effects. In this article, the authors model a maximum possible dose of mycotoxins
      that could be inhaled in 24 h of continuous exposure to a high concentration of
      mold spores containing the maximum reported concentration of aflatoxins B1 and
      B2, satratoxins G and H, fumitremorgens B and C, verruculogen, and trichoverrols
      A and B. These calculated doses are compared to effects data for the same
      mycotoxins. None of the maximum doses modeled were sufficiently high to cause any
      adverse effect. The model illustrates the inefficiency of delivery of mycotoxins
      via inhalation of mold spores, and suggests that the lack of association between
      mold exposure and mycotoxicoses in indoor environments is due to a requirement
      for extremely high airborne spore levels and extended periods of exposure to
      elicit a response. This model is further evidence that human mycotoxicoses are
      implausible following inhalation exposure to mycotoxins in mold-contaminated
      home, school, or office environments.

PMID- 15162842
TI  - Dermal irritation assessment of three benzene sulfonate compounds.
AB  - Three benzene sulfonate compounds, benzene sulfonate, benzene meta-disulfonate,
      and para-phenol sulfonate, were reported to be present in groundwater sampled
      from residential wells near a former disposal site. Concentrations ranged from <
      0.005 mg/L to 474 mg/L. Acute dermal irritation studies were performed on rabbits
      for each of the three sulfonate compounds to determine if they had the potential
      to cause irritation to the skin of persons using this groundwater for bathing,
      showering, or other uses where skin would be exposed. The studies were performed
      by Toxikon Corporation (Bedford, MA) in accordance with the United States
      Environmental Protection Agency (USEPA)'s 1998 Health Effects Test Guidelines. At
      the highest concentration tested (5000 mg/L), all three sulfonate compounds were
      considered to be slight irritants, producing very slight to mild erythema (Draize
      Score 1). In all cases, the reactions were reversible. At 2000 mg/L, benzene meta
      disulfonate and para-phenol sulfonate caused no irritation and were considered
      not to be irritants. At 2000 mg/L, only benzene sulfonate was considered to be a
      slight irritant, producing a mild erythema that was completely reversible within
      24 hours. Benzene sulfonate was not considered an irritant at 1000 mg/L or at 500
      mg/L. It is important to note that all three sulfonate compounds produced only a
      slight irritation at the highest concentration tested. None of the compounds
      produced a moderate to severe irritation response (i.e., severe erythema, edema).
      Furthermore, any irritation response observed at the highest concentrations
      tested was reversible within 72 hours. The only irritation response observed at
      the second highest dose was also reversible within 24 hours.

PMID- 15162843
TI  - Evidence for competitive inhibition of iodide uptake by perchlorate and
      translocation of perchlorate into the thyroid.
AB  - Various published data sets that investigate the potential effect of exogenous
      perchlorate (ClO4-) on the uptake of iodide in the thyroid and subsequent changes
      in thyroid hormone levels are available. In order to best use the data towards
      the prediction of human health effects resulting from ClO4- exposure, the
      available literature data must be integrated into a self-consistent, coherent,
      and parsimonious quantitative model based on the most likely mode of action of
      perchlorate effect on thyroid function. We submit that the simplest mode of
      action for ClO4- in the thyroid that remains consistent with all available data
      involves competitive inhibition of iodide transport into the thyroid follicle,
      transport of perchlorate into the thyroid follicle against a concentration
      gradient, further transport into the thyroid lumen (where it may again interfere
      with iodide transport), and, finally, passive diffusion back into the blood. We
      believe this description of perchlorate's kinetic behavior should serve as the
      foundation for predictive physiologically based pharmacokinetic (PBPK) models and
      as a working hypothesis for further experimental exploration.

PMID- 15162845
TI  - The involvement of p53 in paraquat-induced apoptosis in human lung epithelial
      like cells.
AB  - To investigate the possible role of p53 in the progression of paraquat-induced
      apoptosis, the authors used two cell lines that were wild-type p53-expressing
      human lung epithelial-like cell line (L132) and a p53-deficient human
      promyelocytic leukemia cell line (U937) and explored the linkage between p53, DNA
      damage, and apoptosis. Following paraquat exposure to L132 cells, the percentage
      of S-phase cells decreased significantly and the expression of p53 protein
      increased, suggesting that entry into S phase from G1 phase was blocked. U937
      cells showed complete resistance to paraquat, although paraquat-evoked initial
      single-stranded DNA breaks was shown equally in either L132 or U937 cells, as
      assessed by single-cell gel electrophoresis. U937 and L132 cells die normally
      with similar kinetics when exposed to tumor necrosis factor in the presence of
      cycloheximide, indicating that their capacity to undergo p53-independent
      mechanisms of inducing apoptosis has an equal rate. These results suggest that
      paraquat-induced DNA damage caused G1 arrest and apoptosis only in L132 cells,
      and that p53 protein accumulation is required for the induction of apoptosis by
      paraquat.

PMID- 15162844
TI  - N-acetyltransferase (NAT2) polymorphism and breast cancer susceptibility: a lack
      of association in a case-control study of Turkish population.
AB  - Increased exposure to environmental carcinogens, including several aromatic and
      heterocyclic amines (HAs), is suspected to be one factor contributing to
      incidence of breast cancer. The N-acetyltransferase 2 (NAT2) acetylation
      polymorphism have been associated with a number of drug-induced toxicities and
      cancer in various tissues, resulting from decreased capacity to
      activate/deactivate several aromatic amine, hydrazine drugs, as well as HA
      carcinogens. Ethnic differences exist in NAT2 genotype frequencies, which maybe a
      factor in cancer incidence. Our present case-control study in Turkey was
      performed to explore the association between NAT2 genetic polymorphism and
      individual susceptibility to breast cancer. The NAT2 genotypes (*4, *12A, *5A,
      *5B, *5C, *6, *7) were determined using the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) assay in 84 breast cancer patients and
      103 healthy controls, and 50% and 56.3%, respectively, were found to be slow
      acetylator genotypes. There was no significant difference in risk for breast
      cancer development among patients with rapid and slow acetylators, with adjusted
      odds ratio 0.78 (95% confidence interval 0.44 to 1.38). Also, risk was not
      affected by different variables. To our knowledge, this is the first genetic
      study on the association of NAT2 genotypes with breast cancer in the TUrkish
      population, and this finding showed that NAT2 polymorphism does not play an
      important role in breast cancer risk of Turkish women by altering the capacity in
      deactivation of environmental carcinogens, even though small sample size and wide
      confidence interval.

PMID- 15162846
TI  - Acute and genotoxic profile of a dimeric impurity of cefotaxime.
AB  - The manufacturing and storage of cefotaxime produces different impurities of
      various concentrations, which may influence the efficacy and safety of the drugs.
      Because no report of toxicity data is available on the impurities of cefotaxime,
      the present acute and genotoxicity studies were designed and conducted to provide
      the information for establishing the safety profile and qualification of the
      dimeric impurity. Histidine-requiring mutants of Salmonella typhimurium TA97a,
      TA98, TA100, TA102, and TA1535 strains, with or without metabolic activation (S
      91, were used for point-mutation tests. Neither increase in numbers of
      revertants, indicative of mutagenic activity, nor inhibition of bacterial growth,
      indicative of cytotoxicity, was observed when the dimeric impurity of cefotaxime
      at concentrations of 0.62, 1.85, 5.56, 16.67, and 50 microg/plate was
      incorporated into plates containing S. typhimurium bacterial strains. Cultures of
      Chinese hamster ovary (CHO) cells at a cell density of 2 x 10(5) cells per
      culture were exposed to the dimeric impurity of cefotaxime at the concentration
      of 11.25, 22.5, and 45 mg per culture, with or without metabolic activation, and
      harvested at 18 h after exposure. No chromosomal aberrations in the cultured
      mammalian cells were recorded. Acute intramuscular administration of the dimeric
      impurity of cefotaxime in Sprague-Dawley rats did not result in any clinical
      signs and gross pathological changes up to 2000 mg/kg-body weight. The results of
      these studies indicated that the dimeric impurity of cefotaxime is nonmutagenic
      in Ames test, nonclastogenic in vitro, and acutely nontoxic in rats.

PMID- 15162847
TI  - Fetal ADH2*3, maternal alcohol consumption, and fetal growth.
AB  - There is some evidence suggesting the allele for alcohol dehydrogenase 2*3
      (ADH2*3) is associated with a protective effect against alcohol-related
      intrauterine growth retardation (IUGR). This study was conducted to explore the
      affect of the ADH2*3 allele on fetal growth. Bloodspots (n = 1016) belonging to
      individual infants of a subgroup of the Baltimore-Washington Infant Study (BWIS)
      were assayed for the presence of the ADH2*3 allele by a polymerase chain reaction
      (PCR)-based method. Infants genotyped for ADH2*3 were those for whom bloodspots
      were identified and obtained from the Maryland Newborn Screening Program. The
      effect of ADH2*3 and maternal alcohol consumption on intrauterine growth was
      explored by multivariable linear regression analysis. Twenty-six percent of the
      306 blood spots belonging to African-American infants were positive for ADH2*3
      (4% were homozygous and 22% were heterozygous). Only a small percentage of
      bloodspots for Caucasian (1.3%) were positive for the ADH2*3 allele.
      Consequently, further analysis concentrated on gene-exposure interactions for
      African-American infants. It was found that the incidence of being small-for
      gestation-age (SGA) was lower for ADH2*3-positive infants (2.5% versus 8.8%; p =
      .08). SGA infants had elevated odds for being ADH2*3 negative (OR: 3.15, 95%
      C.I.: 0.70-14.26) and for being born to mothers that consumed alcohol during
      pregnancy (OR: 2.31, 95% C.I.: 0.77-6.91). A negative trend between maternal
      alcohol consumption and mean offspring birthweight was found; however, ADH2*3 did
      not have a significant impact on mean birthweight for infants born to mothers
      that drank during pregnancy. These results could be interpreted as possible
      support for the hypothesis that ADH2 genotype in the infant may impact risk for
      alcohol-related IUGR. However, this study has limitations in that it is a "nested
      study of convenience" and involves a relatively small number of infants born to
      mothers reporting moderate to heavy alcohol use during pregnancy.

PMID- 15162849
TI  - Determination of mercury by cold vapor atomic absorption spectrophotometer in
      Tongkat Ali preparations obtained in Malaysia.
AB  - The DCA (Drug Control Authority), Malaysia, has implemented the phase 3
      registration of traditional medicines on 1 January 1992, with special emphasis on
      the quality, efficacy, and safety (including the presence of heavy metals) in all
      pharmaceutical dosage forms of traditional medicine preparations. As such, a
      total of 100 products in various pharmaceutical dosage forms of a herbal
      preparation, containing Tongkat Ali, were analyzed for mercury content using cold
      vapor atomic absorption spectrophotometer. Results showed that 36% of the above
      products possessed 0.52 to 5.30 ppm of mercury and, therefore, do not comply with
      the quality requirement for traditional medicines in Malaysia. Out of these 36
      products, 5 products that possessed 1.05 to 4.41 ppm of mercury were in fact have
      already registered with the DCA, Malaysia. However, the rest of the products that
      contain 0.52 to 5.30 ppm of mercury still have not registered with the DCA,
      Malaysia. Although this study showed that only 64% of the products complied with
      the quality requirement for traditional medicines in Malaysia pertaining to
      mercury, they cannot be assumed safe from mercury contamination because of batch
      to-batch inconsistency.

PMID- 15162848
TI  - Toxicity of methanol to fish, crustacean, oligochaete worm, and aquatic
      ecosystem.
AB  - Static renewal bioassays were conducted in the laboratory and in outdoor
      artificial enclosures to evaluate toxic effects of methanol to one teleost fish
      and two aquatic invertebrates and to limnological variables of aquatic ecosystem.
      Ninety-six-hour acute toxicity tests revealed cladoceran crustacea Moina micrura
      as the most sensitive to methanol (LC50, 4.82 g/L), followed by freshwater
      teleost Oreochromis mossambicus (LC50, 15.32 g/L) and oligochaete worm Branchiura
      sowerbyi (LC50, 54.89 g/L). The fish, when exposed to lethal concentrations of
      methanol, showed difficulties in respiration and swimming. The oligochaete body
      wrinkled and fragmented under lethal exposure of methanol. Effects of five
      sublethal concentrations of methanol (0, 23.75, 47.49, 736.10, and 1527.60 mg/L)
      on the feeding rate of the fish and on its growth and reproduction were evaluated
      by separate bioassays. Ninety-six-hour bioassays in the laboratory showed
      significant reduction in the appetite of fish when exposed to 736.10 mg/L or
      higher concentrations of methanol. Chronic toxicity bioassays (90 days) in
      outdoor enclosures showed a reduction in growth, maturity index and fecundity of
      fish at 47.49 mg/L or higher concentrations of methanol. Primary productivity,
      phytoplankton population, and alkalinity of water were also reduced at these
      concentrations. Chronic exposure to 1527.60 mg/L methanol resulted in damages of
      the epithelium of primary and secondary gill lamellae of the fish. The results
      revealed 23.75 mg/L as the no-observed-effect concentration (NOEC) of methanol to
      freshwater aquatic ecosystem.

PMID- 15162850
TI  - The man-nature relationship and environmental ethics.
AB  - Our behaviour and policies with regard to nature and the environment should be
      guided by a code of ethics, which is to be derived from basic principles and from
      a pragmatic consideration of the issues at stake. The man-nature relationship has
      always been ambiguous, nature being seen as both a provider and an enemy. In the
      Judeo-Christian tradition, man is set apart from nature and called to dominate
      it, although this attitude has been revised to become one of stewardship.
      Oriental religions, on the other hand, have a more holistic view and consider
      humans as an integral part of nature. Modern philosophers have views ranging from
      anthropocentrism to biocentrism and egocentrism. It is suggested to take a
      pragmatic approach by which primary human needs are met first and foremost
      whereas the needs of other living organisms and ecosystems are allowed to prevail
      over secondary human needs. A plea is made to support the Earth Charter, which
      embodies in its principles and prescriptions a balanced respect for nature and
      future human generations.

PMID- 15162851
TI  - Environmental monitoring and radioecology: a necessary synergy.
AB  - Environmental monitoring primarily aims through sampling or by the use of direct
      detection equipment to quantify the levels of radioactive substances and ionising
      radiation resulting from human activities and natural sources in the different
      compartments of the environment. Its objectives are very practical and include
      the quantification of the environmental sources of ionising radiation and the
      verification of compliance with regulatory requirements and permit limits for
      industrial, research and medical activities, as stated by their specific licence.
      Radioecology is a multidisciplinary science, which attempts to understand and to
      quantify the behaviour of radionuclides in the environment and the processes
      ruling their transport through natural and agricultural ecosystems to various
      receptors such as plants, animals and humans. A second facet of this science
      covers the assessment of the radiological dose to and effects on man and its
      environment from present, past or future, even hypothetical, nuclear activities.
      Despite their different immediate objectives, environmental monitoring and
      radioecology are complementary. Many examples illustrate the connections between
      these two approaches. For instance, transfer parameters generated by
      radioecological studies are necessary to estimate through models the radiological
      exposure of population, derive from the contamination level measured in a bio
      indicator the quantity of radioactivity released from a nuclear installation, or
      identify potentially important pathways to be monitored. On the other hand,
      monitoring data will confirm important pathways suggested by radioecological
      modelling and provide site-specific data for the estimation of model parameters
      or actual data sets for the validation of transfer models.

PMID- 15162852
TI  - Monitoring of radionuclides contamination of soils in Shatsk National Natural
      Park (Volyn region, Ukraine) during 1994-2001.
AB  - The results of studies of radionuclide contamination of the soils in the western
      part of the territory of Shatsk National Natural Park (ShNNP), Volyn region,
      Ukraine, performed during 1994-2001 are presented. Based on the experimental
      results, the three-dimensional plot of the 137Cs density contamination for the
      soils at the territory under investigation has been constructed. The monitoring
      during 1994-2001 of the 137Cs vertical distributions in the different kinds of
      soils from the Park and the forecasting of the distribution changes of the depth
      down to 50 cm for the sod loamy sandy gleyed loamy sand soil of the Park up to
      2086 have been performed.

PMID- 15162853
TI  - Environmental impact of coal industry and thermal power plants in India.
AB  - Coal is the only natural resource and fossil fuel available in abundance in
      India. Consequently, it is used widely as a thermal energy source and also as
      fuel for thermal power plants producing electricity. India has about 90,000 MW
      installed capacity for electricity generation, of which more than 70% is produced
      by coal-based thermal power plants. Hydro-electricity contributes about 25%, and
      the remaining is mostly from nuclear power plants (NPPs). The problems associated
      with the use of coal are low calorific value and very high ash content. The ash
      content is as high as 55-60%, with an average value of about 35-40%. Further,
      most of the coal is located in the eastern parts of the country and requires
      transportation over long distances, mostly by trains, which run on diesel. About
      70% oil is imported and is a big drain on India's hard currency. In the
      foreseeable future, there is no other option likely to be available, as the
      nuclear power programme envisages installing 20,000 MWe by the year 2020, when it
      will still be around 5% of the installed capacity. Hence, attempts are being made
      to reduce the adverse environmental and ecological impact of coal-fired power
      plants. The installed electricity generating capacity has to increase very
      rapidly (at present around 8-10% per annum), as India has one of the lowest per
      capita electricity consumptions. Therefore, the problems for the future are
      formidable from ecological, radio-ecological and pollution viewpoints. A similar
      situation exists in many developing countries of the region, including the
      People's Republic of China, where coal is used extensively. The paper highlights
      some of these problems with the data generated in the author's laboratory and
      gives a brief description of the solutions being attempted. The extent of global
      warming in this century will be determined by how developing countries like India
      manage their energy generation plans. Some of the recommendations have been
      implemented for new plants, and the situation in the new plants is much better. A
      few coal washeries have also been established. It will be quite some time before
      the steps to improve the environmental releases are implemented in older plants
      and several coal mines due to resource constraints.

PMID- 15162854
TI  - Phytoextraction for clean-up of low-level uranium contaminated soil evaluated.
AB  - Spills in the nuclear fuel cycle have led to soil contamination with uranium. In
      case of small contamination just above release levels, low-cost yet sufficiently
      efficient remedial measures are recommended. This study was executed to test if
      low-level U contaminated sandy soil from a nuclear fuel processing site could be
      phytoextracted in order to attain the required release limits. Two soils were
      tested: a control soil (317 Bq 238U kg(-1)) and the same soil washed with
      bicarbonate (69 Bq 238U kg(-1)). Ryegrass (Lolium perenne cv. Melvina) and Indian
      mustard (Brassica juncea cv. Vitasso) were used as test plants. The annual
      removal of soil activity by the biomass was less than 0.1%. The addition of
      citric acid (25 mmol kg(-1)) 1 week before the harvest increased U uptake up to
      500-fold. With a ryegrass and mustard yield of 15,000 and 10,000 kg ha(-1),
      respectively, up to 3.5% and 4.6% of the soil activity could be removed annually
      by the biomass. With a desired activity reduction level of 1.5 and 5 for the
      bicarbonate-washed and control soil, respectively, it would take 10-50 years to
      attain the release limit. However, citric acid addition resulted in a decreased
      dry weight production.

PMID- 15162855
TI  - Comparison of different methods for uranium determination in water.
AB  - Photometry, laser photometry, liquid scintillation (LSC), gamma spectrometry and
      alpha spectrometry were used for estimating waterborne uranium concentration. The
      chemical procedures applied were pre-concentration, liquid extraction,
      chromatographic resin extraction and precipitation. Our results show that laser
      photometry is an easy and accurate method capable of estimating low uranium
      concentrations, parts of micrograms per litre. It is not applicable for higher
      concentrations, difficult water matrixes and isotope determination. The classical
      photometry is complementary, resolving the problem related to high
      concentrations, practically up to 10 mg/l. Alpha and gamma spectrometry resolve
      the problem of precise isotope determination, but with the disadvantage of hard
      chemical preparation and long measurement times. An intermediate method is LSC,
      with the problem of isotope estimation, due to poor energy resolution.

PMID- 15162856
TI  - A common approach for radiological protection of humans and the environment.
AB  - Protection of the environment is developing rapidly at the national and
      international level, but there are still no internationally agreed
      recommendations as to how radiological protection of the environment should be
      carried out. The International Commission on Radiological Protection (ICRP) is
      currently reviewing its existing recommendations for human protection. It has set
      up a task group with the aim of developing a protection policy for, and
      suggesting a framework of, the protection of the environment that could feed into
      its recommendations at the start of the 21st century. The task group will propose
      a framework for the protection of the environment from harmful effects of
      radiation, harmonising with the principles for the protection of humans. Although
      the task group has not yet finalised on the objectives for the environment, these
      might be to safeguard the environment by preventing or reducing the frequency of
      effects likely to cause early mortality, reduced reproductive success, or the
      occurrence of scorable DNA damage in individual fauna and flora to a level where
      they would have a negligible impact on conservation of species, maintenance of
      biodiversity, or the health and status of natural habitats or communities. To
      achieve these objectives, a set of reference dose models, reference dose per unit
      intake and reference organisms will be required.

PMID- 15162857
TI  - Environmental radiation protection: philosophy, monitoring and standards.
AB  - The Euratom Treaty confers important powers to the European Commission with
      regard to monitoring and assessment of levels of radioactivity in the environment
      and discharges with effluents (Articles 35-37 of the Euratom Treaty). Current
      developments in the area relate to harmonised reporting of environmental data and
      to harmonisation of effluent monitoring data. Both developments relate to the
      requirement under the new Basic Safety Standards (BSS) for a realistic assessment
      of population exposure. Guidance to this effect is being prepared by the Article
      31 Group of Experts. In the context of Article 36 intercomparison exercises for
      radionuclides measurements in environmental samples are organised. New challenges
      for environmental monitoring result from the requirement under the BSS to
      regulate also industries processing NORM materials. Also the international move
      towards extending the scope of environmental radioactivity to the protection of
      biota opens new perspectives.

PMID- 15162858
TI  - Overview of the Belgian programme for the surveillance of the territory and the
      implications of the international recommendations or directives on the monitoring
      programme.
AB  - The Royal Decree of 20th July has entrusted the Federal Agency for Nuclear
      Control (FANC) with the task of controlling the territorial radioactivity and the
      doses received by the population. Within this agenda, a monitoring programme has
      been developed over many years, in order to follow the main potential exposure
      pathways of the population. In practice, several potential vectors of
      contamination are controlled: air (and rain), surface water (including sediments
      and biota), soils around nuclear installations, food chain, drinking water etc.
      To carry out such work, the FANC has collaborated with public or private
      reputable organisations: The Centre of Nuclear Energy Studies of Mol, The
      National Institute of Radionuclides of Fleurus, and The Louis Pasteur Public
      Health Institute of Brussels. A synthesis of this monitoring programme will be
      presented and the most important deductions will be pointed out. For many years,
      the tendency has been for tighter control of artificial and natural radioactivity
      in the environment. This has been achieved by increasingly stringent regulations,
      regarding environmental monitoring efforts, from international organisations (EC,
      OSPAR, IAEA). In this context, the FANC in Belgium, is involved in a process that
      will lead to the adaptation of the Belgian monitoring programme. Different
      aspects of these adaptations and of their consequences will be presented for
      illustrative purposes.

PMID- 15162859
TI  - Evolution of the regulation of the environmental radiation protection and
      monitoring in the Russian Federation.
AB  - The evolution of the Russian Federation legislation and regulation concerning the
      radiation protection of the population, the environment and the monitoring is
      presented. The main federal laws--"On the Environmental Protection", "On the
      Atomic Energy Use", "On the Radiation Safety of Population", etc. as well as
      standards of radiation safety, sanitary and hygienic norms, international
      agreements and conventions are briefly summarized. Main directions towards
      further improvement of the environmental radioprotection regulation in Russia are
      pointed out.

PMID- 15162860
TI  - Regulation of nuclear radiation exposures in India.
AB  - India has a long-term program of wide spread applications of nuclear radiations
      and radioactive sources for peaceful applications in medicine, industry,
      agriculture and research and is already having several thousand places in the
      country where such sources are being routinely used. These places are mostly
      outside the Department of Atomic Energy (DAE) installations. DAE supplies such
      sources. The most important application of nuclear energy in DAE is in
      electricity generation through nuclear power plants. Fourteen such plants are
      operating and many new plants are at various stages of construction. In view of
      the above mentioned wide spread applications, Indian parliament through an Act,
      called Atomic Energy Act, 1964 created an autonomous body called Atomic Energy
      Regulatory Board (AERB) with comprehensive authority and powers. This Board
      issues codes, guides, manuals, etc., to regulate such installations so as to
      ensure safe use of such sources and personnel engaged in such installations and
      environment receives radiation exposures within the upper bounds prescribed by
      them. Periodic reports are submitted to AERB to demonstrate compliance of its
      directives. Health, Safety and Environment Group of Bhabha Atomic Research
      Centres, Mumbai carries out necessary surveillance and monitoring of all
      installations of the DAE on a routine basis and also periodic inspections of
      other installations using radiation sources. Some of the nuclear fuel cycle
      plants like nuclear power plants and fuel reprocessing involve large radioactive
      source inventories and have potential of accidental release of radioactivity into
      the environment, an Environmental Surveillance Laboratory (ESL) is set up at each
      such site much before the facility goes into operation. These ESL's collect
      baseline data and monitor the environment throughout the life of the facilities
      including the decommissioning stage. The data is provided to AERB and is
      available to members of the public. In addition, a multi-tier system of AERB
      permissions is in place to ensure that all aspects of safety have been considered
      before permission to operate is granted. The stages where permission of AERB is
      essential are site selection, design data, and several stages during construction
      and operation. The details required by AERB include provision for treatment and
      storage of radioactive waste, de-commissioning procedures and provision of costs.
      In addition to AERB, nuclear power plants have to comply with the requirements of
      Ministry of Environment and Forests and get their clearance. This is given on the
      basis of Environmental Impact Assessment Report which should satisfy the
      authorities that no ecological damage will be caused and the facility will not
      have adverse effect on the environment. In addition, the State Pollution Control
      Board where the facility is to be located has to permit the site of the plant for
      its proposed discharges into the environment. It is largely due to the above
      comprehensive regulatory controls that none of the plants in India had any
      accident during the last 34 decades of operation. The type of measurements
      carried out by the ESL's and results from a few typical ESL's will be presented.

PMID- 15162861
TI  - Continuous radioactivity monitoring systems. From the pre-history of
      radioprotection to the future of radioecology.
AB  - The first significant quantities of artificial radioactivity appeared in the
      environment around the end of the 1940s. They were gigantic and their metrology
      very quickly seemed to be essential for sanitary and military reasons. In the
      1950s, the first continuous monitoring systems of "fall out" were created. They
      were neither automatic nor sensitive and radioprotection of the environment was
      not a concern only for simple public information. Since then, radioecology,
      technology and evolution of our mentality have completely modified our way of
      thinking. Thus, from the 1980s up to the dawn of the new millennium, the gap
      between the performances of metrology laboratories and certain aspects of direct
      measurement has almost disappeared. 1986 certainly contributed a lot to the
      concept of surveillance networks and alarm systems, emphasising that the major
      advantage of these is the fact that they are operational, the minute before the
      accident.

PMID- 15162862
TI  - Status report on standard-setting work in the area of environmental radioactivity
      measurement.
AB  - Environmental assessment studies are regularly commissioned to study the impact
      of radioactive substances on the environment and the public, in response to
      concern about the presence of such substances. The credibility of such studies
      relies on the quality and reliability of radionuclide analysis as well as the
      sample representativity of the radiological situation. The recent expansion from
      national stakeholders to those involving other states requires that activity
      measured in effluents or environmental samples in a country are reliable and
      reproducible so as to be accepted by all states potentially concerned by regional
      contamination. The standard-setting approach, based on consensus, seemed to lend
      itself to a settlement of technical aspects of potential dispute. This document
      describes standardization organizations, French and international, the standards
      published, as well as standardization work under way on the measurement of
      radionuclides found in environmental matrices.

PMID- 15162863
TI  - Monitoring and management of mountain environment.
AB  - The monitoring of mountain environment gives necessary information for its
      control and effective management in view of its sustainable development. A system
      of complex monitoring of environment has been established, including physical,
      chemical, meteorological, hydrological, biological and sociological factors.
      Methods and observations have been developed and applied. Using a geographical
      information system, a database was created for Rila Mountain and a modern
      computer network connected to internet was established. As a direct consequence
      of the French-Bulgarian project OM2 (carried out in the period 1993-1998) a Basic
      Environmental Observatory (on the peak Moussala, 2925 m) was constructed and put
      in operation in attempt to control the large scale and long-term transportation
      of atmospheric pollutants.

PMID- 15162864
TI  - Atmospheric xenon radioactive isotope monitoring.
AB  - The Comprehensive Nuclear Test Ban Treaty (CTBT) organisation is implementing a
      world-wide monitoring network in order to check that the State Signatories comply
      with the treaty. One of the monitoring facilities consists of an atmospheric
      noble gas monitoring equipment. According to the requirements annexed in the
      treaty, the French Atomic Energy Commission (CEA) developed a device, called
      SPALAX, which automatically extracts xenon from ambient air and makes in situ
      measurements of the activities of four xenon radioisotopes (131mXe, 133mXe,
      133Xe, 135Xe). The originality of this device is noticeable essentially in the
      gas sample processing method: thanks to the coupling of a gas permeator and of a
      noble gas specific adsorbent, it can selectively extract and concentrate xenon to
      more than 3 x 10 E6. This process is carried out continuously without cryogenic
      cooling, without any regeneration time. The detection of the xenon radioactive
      isotopes is done automatically by high spectral resolution gamma spectrometry, a
      robust technology well-suited for on-field instrumentation. In the year 2000, a
      prototype was involved in an international evaluation exercise directed by the
      CTBT organisation (CTBTO). This exercise demonstrated that the SPALAX equipment
      perfectly met the requirements of the CTBTO for such systems. On the basis of the
      continuous 24-h resolution record of the atmospheric xenon radioactive isotopes
      concentrations, the SPALAX system also demonstrated that ambient levels of 133Xe
      can fluctuate quickly from less than the detection limit to over 40 x 10(-3) Bq
      m(-3). In order to build an industrial version of this equipment, the CEA entered
      into a partnership with a French engineering company (S.F.I., Marseille, France),
      which is now able to produce an industrial version of SPALAX, i.e. more compact
      and more efficient than the prototypes. The 133Xe minimum detectable
      concentration is 0.15 x 10(-3) Bq m(-3) air per 24 h sampling cycle.

PMID- 15162865
TI  - In situ metrology of 85Kr plumes released by the COGEMA La Hague nuclear
      reprocessing plant.
AB  - The IRSN (Institut de Radioprotection et de Surete Nucleaire, France) has started
      an in situ study of the behaviour of atmospheric releases close-by the COGEMA La
      Hague nuclear reprocessing plant. The study is designed to improve information on
      the dispersion of radioactive pollutants very close to the emission point--a 100
      m height chimney. In this situation, close to the emission and height of the
      emission, Gaussian models generally used to predict the behaviour of atmospheric
      releases are not well adapted. The study is based on the characterisation of the
      85Kr emitted during normal operations of the reprocessing process. Temporal and
      spatial variations of the plume shape were investigated with intensive in situ
      measurements. Live in situ techniques to measure the electrons and the photons
      emitted by the 85Kr have been implemented and will be described. Preliminary
      results showing the interest of the techniques were presented. Variations of the
      dose rates created by the photon flux of a plume were directly measured and
      correlated to other quantities.

PMID- 15162866
TI  - The importance of recording physical and chemical variables simultaneously with
      remote radiological surveillance of aquatic systems: a perspective for
      environmental modelling.
AB  - Modern nuclear metrological tools allow the remote surveillance of the
      radiological status of the aquatic systems, providing an important advance in the
      protection of the environment. Nevertheless, the significance of the radiological
      data could be highly improved through simultaneous recording of physical and
      chemical variables that govern the behaviour and bioavailability of radionuclides
      in these aquatic systems. This work reviews some of these variables from the
      point of view of the environmental modelling. The amount, nature and dynamics of
      the suspended loads and bottom sediments strongly influence the behaviour of
      particle-reactive radionuclides. The kinetics of this process has a very fast
      component, as it is shown from our recent studies with 241Am, 239Pu and 133Ba in
      several aquatic systems from southern Spain. Changes in pH, temperature and in
      the electrical conductivity are influencing the uptake kinetics and the final
      partitioning of the radioactivity. Water currents govern the radionuclide
      transport and dispersion. These points are illustrated with modelling exercises
      in the scenarios of the Suez Canal (Egypt) and the Harsvatten Lake (Sweden).

PMID- 15162867
TI  - POSEIDON/RODOS models for radiological assessment of marine environment after
      accidental releases: application to coastal areas of the Baltic, Black and North
      Seas.
AB  - In the framework of the developments of the European system RODOS (Real-time On
      line DecisiOn support System) for emergency response to nuclear accident, the
      computer code POSEIDON, that was developed to assess the radiological
      consequences of radioactive releases into marine environment, was adapted to cope
      with emergency conditions, in situations of radioactive discharges into the
      oceans from direct deposition from the atmosphere, sunken ships and containers,
      from discharges of rivers and estuaries and from coastal run-off. Based on the
      box model developed within the 'Marina' project, POSEIDON can calculate the dose
      effects from radionuclide releases in the coastal waters of Europe integrated
      over long time periods. A dynamic food chain model was implemented to deal with
      the short-term dynamical uptake of radioactivity by specific marine plants and
      organisms. POSEIDON has been installed on a UNIX platform to be fully compatible
      with RODOS input/output databases and on a Windows platform with an interface
      based on web technology. The 3D hydrodynamic model THREETOX is a part of the
      POSEIDON/RODOS system. It has been applied to coastal areas of the Baltic Sea,
      the Black Sea, and the North Sea. to derive the parameters for a flexible system
      of well-defined model compartments to be adapted to emergency conditions. The
      activity concentrations in water and in the marine food web were calculated by
      means of POSEIDON for radioactive fallout resulting from bomb testing, from the
      Chernobyl accident, and from routine discharges from nuclear facilities.
      POSEIDON's model results were compared with measurement data, and with
      calculation results from THREETOX. The model results agreed with the measurement
      data sufficiently.

PMID- 15162868
TI  - Monte Carlo calculation of entire in situ gamma-ray spectra.
AB  - We present a method for the synthesis of entire in situ gamma-ray spectra based
      on Monte Carlo calculations and measured data that characterize the detector
      properties. The method can serve for the determination of the effective depth of
      137Cs in soil based on the information contained in the low-energy part of an in
      situ spectrum. Effective depth is defined as the depth of a plane distribution of
      137Cs beneath the surface that reproduces the fluence energy and angular
      distribution at 1 m above the ground of gamma rays belonging to the real 137Cs
      distributions. We managed to reproduce the measured in situ spectra with our
      method and to demonstrate that the method allows the determination of the
      effective depth of 137Cs with a precision of 10(-2) m. The method requires
      minimal experimental characterization of the detector and is not sensitive to the
      details of the detector model and the soil composition and density employed in
      the Monte Carlo calculations.

PMID- 15162869
TI  - Sector field inductively coupled plasma mass spectrometry, another tool for
      plutonium isotopes and plutonium isotope ratios determination in environmental
      matrices.
AB  - The transfer of radio nuclides into the different compartments of the environment
      are widely studied and leads to the elaboration of transfer models in order to
      evaluate potential impact onto the environment and humans. Accurate experimental
      data are needed to validate these models for all types of matrices (air, water,
      sediments, soils, biota and food...). Among these radionuclides, 238Pu, 239Pu,
      240Pu and 241Pu, are often mentioned. They have been released into the
      environment by nuclear weapon tests, nuclear facilities, reactors or satellite
      accidents. These different sources have different 240Pu/239Pu ratios and
      therefore this ratio is used to provide information on the source of
      contamination into the environment. The most conventional analytical tools used
      for plutonium isotope determination are liquid scintillation and alpha
      spectrometry, and thermal ionisation mass spectrometry (TIMS) is still considered
      as the primary method for determination of plutonium isotope ratios. During the
      last decade, mass spectrometers equipped with plasma ion sources and sector field
      analysers were developed and can offer now another alternative method for the
      accurate determination of isotope content and ratios of long-lived radionuclides
      in environmental samples. This paper presents and discusses the results obtained
      for 239Pu, 240Pu and 241Pu content and isotope ratios by sector field ICP-MS in
      different environmental matrices.

PMID- 15162870
TI  - Performance level of an autonomous system of continuous monitoring of
      radioactivity in seawater.
AB  - Following the recognition of their usefulness by the authorities and the
      scientific community, automatic water monitoring networks were developed again to
      be able to measure seawater. For that purpose, they had to be fully autonomous,
      with low power consumption (solar panel power supply), wireless communicating
      (satellite, GSM, radio) and very sensitive (a few Bq/m3).

PMID- 15162871
TI  - Direct methods for radionuclides measurement in water environment.
AB  - The paper is devoted to the direct method of anthropogenic radionuclide
      measurement in the water environment. Opportunities of application of submersible
      gamma-spectrometers for in situ underwater measurements of gamma-radiating
      nuclides and also the direct method for 90Sr detection are considered.

PMID- 15162872
TI  - High accuracy in situ radiometric mapping.
AB  - In situ and airborne gamma ray spectrometry have been shown to provide rapid and
      spatially representative estimates of environmental radioactivity across a range
      of landscapes. However, one of the principal limitations of this technique has
      been the influence of changes in the vertical distribution of the source (e.g.
      137Cs) on the observed photon fluence resulting in a significant reduction in the
      accuracy of the in situ activity measurement. A flexible approach for single
      gamma photon emitting radionuclides is presented, which relies on the
      quantification of forward scattering (or valley region between the full energy
      peak and Compton edge) within the gamma ray spectrum to compensate for changes in
      the 137Cs vertical activity distribution. This novel in situ method lends itself
      to the mapping of activity concentrations in environments that exhibit systematic
      changes in the vertical activity distribution. The robustness of this approach
      has been demonstrated in a salt marsh environment on the Solway coast, SW
      Scotland, with both a 7.6 cm x 7.6 cm NaI(Tl) detector and a 35% n-type HPGe
      detector. Application to ploughed field environments has also been demonstrated
      using HPGe detector, including its application to the estimation of field moist
      bulk density and soil erosion measurement. Ongoing research work is also
      outlined.

PMID- 15162873
TI  - Experience with airborne detection of radioactive pollution (ENMOS, IRIS).
AB  - This paper discusses the advantages of airborne monitoring of radioactive
      pollution and shows example maps indicating manmade pollution from different
      sources. The sensitivity of airborne radioactive detection is discussed.
      Comparisons of airborne and different ground measurements are presented. New
      instrumentation for airborne or ground moving vehicles is briefly described.
      Airborne footprinting provides rapid, well-defined spatial images of natural and
      manmade radioactive contamination. Data acquisition integrated with GPS
      navigation provides consistent data and guarantees proper data location. Real
      time airborne measurements are re-calculated, with the use of special algorithms,
      into absolute units for individual radioactive nuclei contamination of the ground
      together with dose calculation. Raw records and calculated data are provided
      after enhanced post-flight processing. Dose rates and detection of different
      radioactive elements are presented. (ENMOS is a product of Picodas Group Inc. and
      IRIS is the product of Pico Envirotec Inc.)

PMID- 15162874
TI  - An airborne gamma-ray spectrometry survey of nuclear sites in Belgium.
AB  - As part of a wider study to define the existing background levels in Belgium an
      airborne gamma-ray survey was conducted in two areas associated with nuclear
      sites. In the Mol area, the survey zone included areas surrounding the SCK-CEN
      nuclear research centre, and its associated neighbourhood which includes
      radioactive waste stores, fuel manufacture and fabrication facilities and an
      international accelerator laboratory. In the vicinity of Fleurus, the survey
      included the IRE complex with radiochemical laboratories, irradiation facilities
      and stores, and isotope production accelerators. The survey was conducted using a
      twin engined helicopter equipped with a combined scintillation and semiconductor
      spectrometer. The system was installed and tested in the UK, and then transferred
      to Belgium for operations. The complete survey was conducted successfully within
      1 week. The results provide a comprehensive record of the radiation environment
      of the nuclear sites at time of survey, and show a range of signals associated
      with the types of activity present in each area. They confirm that radiation
      fields are largely confined to the operational sites, and provide a traceable
      record against which future changes could be assessed. The demonstration of
      efficient deployment between two European countries, coupled with rapid mapping
      of many different radiometric signals around these sites confirms the utility of
      the airborne gamma spectrometry approach for accurate definition of enhanced
      radiation fields. This has important implications for emergency response.

PMID- 15162875
TI  - Aerial measurements of artificial radionuclides in Germany in case of a nuclear
      accident.
AB  - Gamma-ray spectrometric systems carried by helicopters prove to be indispensable
      for the surveillance of environmental radioactivity. The aerial measurements are
      an important tool for rapid and large-scale nuclide specific determination of
      soil contamination after an accidental release of radionuclides from a nuclear
      facility. Furthermore this technique is also applied for the determination of
      anomalies of elevated radioactivity of natural radionuclides, the detection of
      lost radioactive sources and geological mapping. For the measurements the
      helicopters are equipped with a NaI(Tl)-detector array and a high purity
      germanium-semiconductor (HPGe) detector. Especially with the HPGe-detector it is
      possible to clearly identify individual radionuclides. To improve and to
      guarantee the quality of this method several exercises with different fields of
      interest have been carried out during the last years. Thereby the main focus is
      on the improvement of the instrumentation, data handling and data analysis. The
      results of the airborne radionuclide measurements from the Black Forest which was
      performed in co-operation with the Swiss National Emergency Operation Centre, are
      presented here. During this exercise the gamma dose rate, soil contamination due
      to 137Cs and the specific activities of natural radionuclides in soil were
      determined.

PMID- 15162876
TI  - Quality assurance for the measurements and monitoring of radioactivity in the
      environment.
AB  - During the Fifth Framework Programme (FP5) of the European Commission--according
      to an institutional programme in support to the policy of the European Commission
      for the implementation of Art. 35 and 36 of the Euratom Treaty as well as in the
      framework of the OSPAR Convention for the protection of marine environment of the
      north-east Atlantic--at the Institute for Transuranium Elements (ITU--General
      Directorate Joint Research Centre--European Commission), a reference laboratory
      for the measurement of radioactivity in the environment (MaRE laboratory) has
      been set up. In this paper, the principles and philosophy in order to improve the
      quality and reliability of analytical data for the measurement and monitoring of
      radioactivity in the environment under a quality assurance (QA) programme are
      presented. Examples of how a QA programme at the MaRE laboratory is developed and
      applied are given. Internal and external quality control (QC) programmes are also
      discussed.

PMID- 15162877
TI  - The surgical management of thoracolumbar injuries.
AB  - This review addresses the epidemiology, clinical examination, and radiographic
      evaluation and fracture classification of thoracolumbar injuries. The factors
      that indicate surgical intervention and the surgical management of specific
      injuries such as compression fractures, burst fractures, flexion-distraction, and
      fracture-dislocation injuries are described, as well as their potential
      complications. In addition, postoperative management is covered, including deep
      venous thrombosis prophylaxis.

PMID- 15162878
TI  - Significance of bacteriuria in neurogenic bladder.
AB  - OBJECTIVE: To investigate the usefulness of performing routine urine cultures in
      veterans with spinal cord injury (SCI) who come for annual evaluation. RESEARCH
      DESIGN/PARTICIPANTS: This retrospective study was performed on asymptomatic
      patients who came for outpatient annual evaluation. The records of 89 healthy
      male veterans with SCI between the ages of 22 and 82 years (mean age = 50.6) were
      reviewed from March through October 2000. METHODS: The following information was
      collected: patient's name, social security numbers, age, year of injury, level of
      injury, American Spinal Injury Association (ASIA) classification, urinalysis
      including white blood cell (WBC) count and presence or absence of nitrite, urine
      culture results (> or <100,000 colony-forming units of uropathogens per
      milliliter), blood WBC count, and mode of bladder management. The data were
      analyzed statistically to look at the effects of age at injury, level of injury,
      injury category (ASIA classification), pyuria, urinary nitrite, serum WBC count,
      and mode of bladder control on the presence of bacteriuria. RESULTS: Results
      revealed that regardless of the level of injury, individuals with ASIA A injuries
      were at high risk of having bacteriuria with positive culture results. Patients
      who were nitrite positive and/or had > or =6 WBCs per high-powered field (HPF) in
      the urine were also at high risk for significant bacteriuria. CONCLUSION: Urinary
      tract infections (UTIs) in the SCI population frequently are asymptomatic,
      polymicrobial, caused by antibiotic-resistant bacteria, and very likely to recur
      or relapse. However, there are no data to support or justify treatment of
      asymptomatic bacteriuria. The present study suggests that healthy asymptomatic
      patients with SCI who come for annual evaluations should not have routine urine
      cultures if they are at low risk for UTIs; that is, <6 WBC/HPF in the urine
      and/or nitrite negative.

PMID- 15162879
TI  - Life satisfaction following spinal cord injury: long-term follow-up.
AB  - OBJECTIVE: To determine the course of self-reported life satisfaction in a spinal
      cord injury (SCI) cohort. DESIGN: Prospective study using longitudinal data from
      the Injury Control Research Center. PARTICIPANTS: Adult persons with traumatic
      onset SCI (n = 207) evaluated at 1, 2, 4, and 5 years postinjury using the Life
      Satisfaction Index-A. RESULTS: A nonsignificant (P > 0.05) main effect of time
      was found using a repeated-measures analysis controlling for education and
      employment status. Several methods were used that provided a range of liberal to
      conservative estimates for missing data (ie, 38% retention rate at year 5).
      Subsequent missing data analyses tended to corroborate the finding of a
      nonsignificant effect of time, although the most conservative methods showed a
      significant decrease in life satisfaction between year 1 and year 5 postinjury (P
      < 0.05). Examination of numerous demographic, injury, and treatment-related
      characteristics at each follow-up time point suggested that the main findings of
      the study were not merely the result of differential dropout rates. CONCLUSION:
      Life satisfaction after the first year of injury remains largely the same over
      the next 4 years. Methodologic and analytic recommendations are discussed.

PMID- 15162881
TI  - The role of abnormal congenitally displaced ureteral orifices in causing reflux
      following spinal cord injury.
AB  - OBJECTIVE: To determine the role of congenitally displaced ureteral orifices in
      causing vesicoureteral reflux (VUR) in individuals with spinal cord injury (SCI).
      DESIGN: Retrospective chart review. PARTICIPANTS: Men and women with (UMN)
      neurogenic bladders secondary to SCI. MAIN OUTCOME MEASURES: Position of the
      ureteral orifice and urodynamic parameters in association with VUR. METHODS: A
      retrospective chart review was performed to identify SCI participants with and
      without reflux who had evaluation with cystoscopy, cystogram, and urodynamics.
      The position of ureteral orifice was compared in individuals with SCI who did and
      did not have ureteral reflex. All cystogram studies were interpreted by board
      certified radiologists. The International Classification system was used to grade
      the severity of the reflux. Fisher exact test was used to evaluate the
      association of the posterior ureteral orifice and reflux. Analysis also was
      performed to evaluate the association of reflux with posterior-placed ureteral
      orifices and urodynamic parameters in the reflux group and nonreflux group.
      RESULTS: Fifteen participants were found to have reflux--11 had posterior-placed
      ureteral orifices, whereas 4 had normally positioned orifices. The 11 individuals
      with posterior-placed ureteral orifices had no bladder wall trabeculation.
      However, all 4 individuals with normally positioned ureteral orifices had severe
      trabeculation. Seventeen participants did not exhibit reflux--2 had posteriorly
      placed ureteral orifices and 15 had normally positioned orifices. Association of
      posterior position and reflux (P = 0.004). No differences were found with regard
      to bladder capacity, bladder wall compliance, or voiding pressures between the
      reflux group and nonreflux group. CONCLUSION: Congenitally displaced ureteral
      orifices are an important cause of VUR in individuals with SCI. Participants with
      normally positioned ureteral orifices only had reflux in the presence of severe
      trabeculation. This study suggests that annual screening with cystograms may not
      be necessary in individuals with normally positioned ureteral orifices and no
      significant trabeculation.

PMID- 15162880
TI  - Alcohol use associated with cervical spinal cord injury.
AB  - OBJECTIVES: To determine whether alcohol use at time of spinal cord injury (SCI)
      is more common with cervical injury than with lower levels of spinal injury.
      METHODS: Veterans and nonveterans with SCI were assessed at a Veteran's Affairs
      Medical Center from 1994 through 2002 and completed a health questionnaire that
      included information on alcohol use at time of traumatic injury. RESULTS: Of 362
      men, 45% had neurologically complete or incomplete cervical injuries.
      Participants with cervical injury were more likely to have used alcohol when
      injured (62/162, 38%) compared with participants without cervical injury (45/200,
      23%). Adjusting for age at injury and accident type, participants with cervical
      SCI had an increased relative odds of having used alcohol at injury compared with
      participants without cervical SCI (2.06, 95% confidence interval = 1.24-3.43).
      CONCLUSION: Alcohol use at time of SCI is a risk factor for cervical injury. This
      finding is of public health concern and should be included in alcohol educational
      programs.

PMID- 15162882
TI  - Upper limb pain in a national sample of veterans with paraplegia.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this survey study was to examine the
      prevalence and intensity of pain and associated patient characteristics in a
      national sample of veterans with paraplegia. Of particular interest were upper
      limb (UL) pain conditions, which pose unique challenges to individuals who use a
      wheelchair for mobility. Because the risk for UL pain conditions appears to
      increase over time, the associations among age, duration of wheelchair use, and
      UL pain were evaluated. METHODS: A group of 1,675 individuals between the ages of
      18 and 65 with a lesion between T2 and L2 and a mailing address on file were
      selected randomly from the Veteran's Affairs Spinal Cord Dysfunction Registry and
      mailed a survey packet. Of the deliverable packets, approximately 46% were
      completed and returned. RESULTS: Approximately 81% of the respondents reported at
      least a minimal level of ongoing unspecified pain and 69% experienced current UL
      pain. Shoulder pain intensity was most severe during the performance of
      wheelchair-related mobility and transportation activities, suggesting that UL
      pain may have a significant impact on functional independence. Duration of
      wheelchair use modestly predicted shoulder pain prevalence and intensity, but age
      and the interaction between age and duration of wheelchair use did not.
      CONCLUSION: The data of the present study suggest that the development,
      persistence, and exacerbation of UL pain conditions in persons with paraplegia
      are multidimensional processes. A comprehensive theoretic model is needed to
      integrate the existing empiric literature in this area.

PMID- 15162884
TI  - Postural hypotension, hyponatremia, and salt and water intake: case reports.
AB  - PURPOSE: Postural hypotension (PH) and hyponatremia are common and often
      coexistent among patients with severe paralysis secondary to spinal cord injury.
      Volume depletion could account for these conditions. This study examined whether
      salt and water intake correlated with the severity of PH. PARTICIPANTS:
      Participants were 4 patients with tetraplegia, motor and sensory complete, aged
      68 to 83 years, who were paralyzed for 9 to 54 years, who had PH. These patients
      were ranked by the amount of ephedrine prescribed on a daily basis to treat PH
      over the preceding 2-year period. METHODS: The total urinary output of sodium and
      water and the effect of orthostasis on urine output rate, osmolality, sodium
      concentration, and creatinine secretion were determined over a 48-hour period of
      collection and compared with severity of PH. RESULTS: The ephedrine requirements,
      in order of decreasing severity of PH, were 100 mg/d, 25 mg/d, 12.5 mg/d, and no
      ephedrine needed. The 24-hour sodium excretions in that order were 50, 92, 180,
      and 164 mEq. The urine volumes were 1.4, 3, 2.6, and 5.4 L, respectively. In the
      same order of decreasing PH severity, the sitting position relative to the
      recumbent position was characterized by increasing rates of creatinine secretion
      (ratios of 0.69, 0.74, 0.95, and 0.80), increasing rates of water excretion
      (ratios of 0.49, 0.28, 0.69, and 0.99), decreasing urine osmolality (ratios of
      1.2, 1.8, 1.3, and 0.8), and increasing sodium concentrations (ratios of 0.9,
      1.3, 1.2, and 2.6). CONCLUSION: In these individuals with tetraplegia, severe PH
      was accompanied by avid conservation of water and impaired retention of sodium in
      the sitting position, as well as limited salt and water intake.

PMID- 15162883
TI  - Nitrite and leukocyte dipstick testing for urinary tract infection in individuals
      with spinal cord injury.
AB  - OBJECTIVE: To determine sensitivity, specificity, and positive and negative
      predictive values of nitrite (NIT) and leukocyte esterase (LE) testing in
      relation to laboratory evidence of significant bacteriuria and urinary tract
      infection (UTI) in persons with spinal cord injury (SCI). DESIGN: Monthly urine
      cultures were compared with results of dipstick testing. SETTING: Community
      based. METHODS: Fifty-six people with SCI were evaluated on a monthly basis with
      dipstick testing for NIT and LE as well as urine cultures. Participants reported
      whether they believed that they had a UTI and, if so, whether they were treated
      for the UTI and what symptoms they had experienced. RESULTS: The sensitivity rate
      for the most comprehensive criteria--defined as positive NIT test, a positive LE
      positive, or both a positive NIT test and positive LE test--was 0.64 and the
      specificity rate was only 0.52. No single type of bacteria was found to occur in
      more than 30% of the urine samples. CONCLUSION: Reliance on dipstick testing for
      NIT and LE in individuals with SCI can lead to high rates of overtreatment for
      UTI, given the fact that regular catheterization is associated with significant
      bacteriuria. Individuals with SCI should be evaluated with urine culture to
      ensure proper treatment.

PMID- 15162885
TI  - Treatment of myofascial shoulder pain in the spinal cord injured population using
      static magnetic fields: a case series.
AB  - OBJECTIVE: Magnetic therapy has been used in the treatment of a wide variety of
      chronic pain syndromes. It has not been studied in the treatment of myofascial
      shoulder pain in persons with spinal cord injury (SCI). Because this type of pain
      is commonly refractory to traditional therapy, alternative treatments often are
      considered. The primary objective is to determine whether myofascial shoulder
      pain in persons with SCI can be temporarily ameliorated with static magnetic
      fields. DESIGN: Case series. SETTING: Clinic of a university hospital system.
      PARTICIPANTS: A volunteer sample of 8 participants with SCI; 3 women, 5 men; mean
      age = 45 years; mean duration of injury = 12.3 years. INTERVENTIONS: Placement of
      a commercially available magnet with a static magnetic field of 500 gauss on the
      affected shoulder for 1 hour. MAIN OUTCOME MEASURES: Pretreatment and
      posttreatment scores on the short-form McGill Pain Questionnaire and pressure
      algometry were compared. RESULTS: The short-form McGill Pain Questionnaire
      descriptors demonstrated significant decreases: stabbing, 0.75 +/- 0.71 (P <
      0.02); sharp, 0.50 +/- 0.53 (P < 0.033); and tender, 0.88 +/- 0.83 (P < 0.021).
      They also demonstrated a significant decrease in the present pain intensity of
      0.63 +/- 0.52 (P < 0.011). Participants demonstrated a nonsignificant decrease of
      0.813 +/- 0.998 (P < 0.55) on the visual analog scale. Pressure algometry was
      nonsignificant with a difference of 0.062 +/- 1.17 (P < 0.885). CONCLUSION:
      Static magnetic fields may decrease the sensory dimensions and intensity of
      myofascial shoulder pain in persons with SCI.

PMID- 15162886
TI  - The effect of electrically induced lower extremity ergometry on an ischial
      pressure ulcer: a case study.
AB  - BACKGROUND: Individuals with spinal cord injury (SCI) are at an increased risk of
      pressure ulcer development. Electrical stimulation of adjacent muscles may be
      underutilized as a tool for pressure ulcer healing in individuals with SCI.
      METHOD: Single case study. SUMMARY: A 27-year-old man with C4 tetraplegia
      developed a left ischial pressure ulcer that for 23 months responded slowly and
      inconsistently to conventional treatment. Electrically induced lower extremity
      ergometry (EILEE) was introduced to facilitate wound healing. The pressure ulcer
      healed completely in 6.5 months. CONCLUSION: This case illustrates the potential
      important contribution of EILEE in the healing of an ischial pressure ulcer in
      individuals with SCI.

PMID- 15162887
TI  - Spinal cord injury: facts and figures at a glance.

PMID- 15162888
TI  - From dialysis outcomes quality initiative to kidney disease outcomes quality
      initiative: new clinical practice guidelines in nephrology--what the practicing
      pharmacist needs to know.
AB  - The use of clinical practice guidelines (CPGs) to guide rational treatment of
      patients is hardly novel to most areas of medicine or pharmacy but is a
      relatively new concept in nephrology where practice patterns have been dictated
      predominantly by opinion. This situation has undergone significant and dramatic
      change in the last few years, however, and CPGs have now been produced to address
      the management problems that face clinicians caring for patients with kidney
      diseases. This is the first of a series of planned articles designed to review
      these new kidney-related CPGs that are most likely to affect the practice of
      pharmacy in many areas. This article provides a broad overview to the background
      of the development of CPGs in nephrology and the methodology used. Subsequent
      articles will identify in some detail current and pending CPGs that relate to
      pharmacotherapy.

PMID- 15162889
TI  - Inhibition of streptokinase-induced, antibody-mediated platelet aggregation with
      tirofiban after exposure to streptokinase or streptococcal infection.
AB  - STUDY OBJECTIVE: To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa
      inhibitor) in preventing streptokinase-induced, antibody-mediated platelet
      aggregation after administration of streptokinase or development of a
      streptococcal infection. DESIGN: Prospective analysis. SETTING: Research center
      of a Canadian hospital. PARTICIPANTS: Forty-five healthy volunteers, 45 patients
      who had received streptokinase within the past 3 years, and 13 patients who had a
      severe streptococcal infection also within the past 3 years. INTERVENTION: Blood
      samples were drawn to measure the extent of inhibition of streptokinase-induced,
      antibody-mediated platelet activation and aggregation by tirofiban. MEASUREMENTS
      AND MAIN RESULTS: Platelet aggregation was measured by using a turbidimetric
      method. The extent of inhibition by tirofiban was measured by incubating
      tirofiban for 2 minutes before adding streptokinase 5000 U/ml. Also, tirofiban
      was added 2 minutes before adding adenosine 5'-diphosphate (ADP) 2 microM/L into
      the last tube as a comparison. Strepto-kinase-induced, antibody-mediated platelet
      aggregation was observed in 10 (22%) of the 45 patients treated with
      streptokinase, in 3 (23%) of the 13 patients with streptococcal infection, and in
      none of the 45 healthy volunteers. Tirofiban inhibited streptokinase-induced,
      antibody-mediated platelet aggregation by 89 +/- 14% (p<0.001). Similarly, ADP
      induced platelet aggregation was inhibited by 92 +/- 6% (p<0.001) with tirofiban.
      CONCLUSION: Streptokinase-induced, antibody-mediated platelet aggregation
      occurred in 13 (22%) of 58 patients who received streptokinase or were exposed to
      a streptococcal infection in the past 3 years. Such patients may not benefit from
      streptokinase therapy. In these patients, tirofiban significantly decreased the
      extent of antistreptokinase antibody-mediated platelet aggregation. Hence,
      patients undergoing streptokinase therapy may benefit from tirofiban as
      adjunctive therapy.

PMID- 15162890
TI  - Tobramycin pharmacokinetics in children with febrile neutropenia undergoing stem
      cell transplantation: once-daily versus thrice-daily administration.
AB  - STUDY OBJECTIVE: To describe the pharmacokinetic disposition of tobramycin in
      children undergoing stem cell transplantation (SCT) after intravenous
      administration either every 24 hours or every 8 hours, and to use this
      information to create initial dosing guidelines for administration every 24 hours
      in this patient population. DESIGN: Pharmacokinetic analysis of a randomized
      controlled trial. SETTING: The Hospital for Sick Children, Toronto, Ontario,
      Canada. PATIENTS: Sixty children (< 18 yrs) with febrile neutropenia undergoing
      stem cell transplantation. INTERVENTION: Patients were randomized to receive
      intravenous tobramycin either every 24 hours (29 patients) or every 8 hours (31
      patients). Initially, they received either 2.5 mg/kg/dose every 8 hours or weight
      based doses by age group (< 5 yrs, 9 mg/kg/dose; 5 to < 12 yrs, 8 mg/kg/dose; >
      or = 12 yrs, 7 mg/kg/dose) every 24 hours. MEASUREMENTS AND MAIN RESULTS: Serum
      tobramycin concentrations were obtained at 2 and 8 hours after the first dose.
      Initial guidelines for dosing every 24 hours were derived using the parameters
      from all patients to achieve a maximum serum concentration (Cmax) of 20-22.5 mg/L
      and a drug-free interval (time during dosing interval when the tobramycin
      concentration was < 1 mg/L) of at least 4 hours. After the first tobramycin dose,
      the elimination rate constant (kel) and volume of distribution (Vd) observed in
      the every-8-hour group (23 patients) were 0.34 +/- 0.09 hours(-1) and 0.48 +/-
      0.21 L/kg, respectively. The kel and Vd in the every-24-hour group (22 patients)
      were 0.43 +/- 0.12 hr(-1) and 0.43 +/- 0.26 L/kg, respectively. Tobramycin Vd
      varied with age. Initial doses of tobramycin every 24 hours recommended to
      achieve the target parameters are 10 mg/kg/dose for patients aged 6 months to
      less than 9 years, 8 mg/kg/dose for those aged 9 to less than 12 years, and 6
      mg/kg/dose for those aged 12 years or older. CONCLUSION: Children undergoing SCT
      who receive tobramycin every 24 hours should receive an initial dose based on
      age. Further validation of the proposed dosing guidelines is required.

PMID- 15162891
TI  - Single-dose pharmacokinetics of sodium ferric gluconate complex in iron-deficient
      subjects.
AB  - STUDY OBJECTIVES: To determine the single-dose pharmacokinetics of intravenous
      sodium ferric gluconate complex in sucrose injection (SFGC) in iron-deficient
      human volunteers, and to assess iron transport. DESIGN: Open-label, randomized
      study. SETTING: Clinical research facility. SUBJECTS: Fourteen iron-deficient men
      and women. INTERVENTIONS: Subjects were randomized to receive a single
      intravenous dose of either SFGC 62.5 mg administered over 30 minutes or SFGC 125
      mg over 60 minutes. Five days later, the same subjects were rerandomized to
      receive a second intravenous dose of SFGC, either 62.5 mg administered over 4
      minutes or 125 mg over 7 minutes. MEASUREMENTS AND MAIN RESULTS: Blood samples
      were collected at predefined times before, during, and up to 72 hours after the
      infusion to determine the single-dose pharmacokinetics of SFGC. Assays were
      performed for both total iron and transferrin-bound iron, from which drug-bound
      iron could be calculated. Urine was collected over 24 hours before dosing and for
      24 hours after the start of infusion to determine the renal elimination of iron.
      Clearance of SFGC from serum was rapid and far exceeded rates reported for iron
      dextran. Pharmacokinetic parameters were unaffected by dose or infusion rate.
      Serum iron derived from SFGC did not exceed the binding capacity of transferrin.
      Serum iron from SFGC became rapidly available (< 24 hrs) as transferrin-bound
      iron, but only after passage through another compartment, presumably the
      reticuloendothelial system (RES). At least 80% of the administered iron was
      transported to bone marrow within 24 hours after infusion. CONCLUSIONS: Iron
      derived from SFGC appears to be rapidly transferred to a bioavailable iron
      compartment as transferrin-bound iron after digestion in the RES. At the doses
      administered in this study, liberation of potentially toxic, free iron was not
      detectable.

PMID- 15162892
TI  - Statins and liver toxicity: a meta-analysis.
AB  - STUDY OBJECTIVE: To assess the risk of liver function test (LFT) abnormalities
      with the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) for the treatment of hyperlipidemia. DESIGN: Meta-analysis of
      randomized, placebo-controlled trials of statins used for the treatment of
      hyperlipidemia or for primary or secondary prevention of cardiovascular disease.
      SETTING: University research center. PATIENTS: A total of 49,275 patients from 13
      trials. INTERVENTION: A literature search of published clinical trials was
      performed in MEDLINE (January 1966-March 2003) and the Cochrane Controlled Trials
      Registry (first quarter 2003). Studies also were identified from the references
      of the trials and of published systematic reviews. MEASUREMENTS AND MAIN RESULTS:
      For a trial to be included in the meta-analysis, its duration of follow-up had to
      be at least 48 weeks and the trial had to include at least 400 patients, with at
      least 200 treated with a statin. Trials conducted in transplant recipients were
      excluded. The proportion of patients having LFT abnormalities was low in both
      groups (statins 1.14% vs placebo 1.05%, odds ratio [OR] 1.26, 95% confidence
      interval [CI] 0.99-1.62, p=0.07). Only fluvastatin was associated with a
      significant increase in the odds of having LFT abnormalities (fluvastatin 1.13%
      vs placebo 0.29%, OR 3.54, 95% CI 1.1-11.6, p=0.04) compared with placebo,
      although this finding was based on only two trials. CONCLUSIONS: Our results
      support previous observations that pravastatin, lovastatin, and simvastatin at
      low-to-moderate doses are not associated with a significant risk of LFT
      abnormalities. Additional data are required to determine whether other statins
      have a similar safety profile.

PMID- 15162895
TI  - Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride.
AB  - Sulfonylureas, which have evolved through two generations since their
      introduction nearly 50 years ago, remain the most frequently prescribed oral
      agents for treatment of patients with type 2 diabetes mellitus. Glyburide,
      glipizide, and glimepiride, the newest sulfonylureas, are as effective at
      lowering plasma glucose concentrations as first-generation agents but are more
      potent, better tolerated, and associated with a lower risk of adverse effects.
      Differences in their binding affinity to the beta-cell sulfonylurea receptor have
      been described, with preservation of cardioprotective responses to ischemia with
      glimepiride. Clinical studies have shown glimepiride to be safe and effective in
      reducing fasting and postprandial glucose levels, as well as glycosylated
      hemoglobin concentrations, with dosages of 1-8 mg/day. In comparative trials,
      glimepiride was as effective in lowering glucose levels as glyburide and
      glipizide, but glimepiride was associated with a reduced likelihood of
      hypoglycemia and a smaller increase in fasting insulin and C-peptide levels than
      glyburide, and a more rapid lowering of fasting plasma glucose levels than
      glipizide. Glimepiride also improves first-phase insulin secretion, which plays
      an important role in reducing postprandial hyperglycemia. Insulin secretagogues,
      specifically glimepiride, merit consideration as first-line therapy for patients
      with type 2 diabetes.

PMID- 15162894
TI  - Effect of age on international normalized ratio at the time of major bleeding in
      patients treated with warfarin.
AB  - STUDY OBJECTIVES: Because the risk of major bleeding associated with warfarin
      increases with increasing international normalized ratio (INR) as well as with
      advanced age, we evaluated the association between age and INR in patients with
      major bleeding events related to anticoagulation with warfarin. DESIGN:
      Retrospective record review. SETTING: Two university-affiliated anticoagulation
      clinics. PATIENTS: Sixty-six patients (mean age 61.2 yrs, range 21-90 yrs)
      receiving warfarin therapy who experienced major bleeding, defined as bleeding
      requiring hospitalization, during a 20-month index period. MEASUREMENTS AND MAIN
      RESULTS: In patients aged 65 years or older, the mean INR at the time of a major
      bleeding event was significantly lower than that in patients younger than 65
      years (INR 3.1 vs 4.2, respectively; p=0.01). For every 1-year increase in age,
      mean INR at the time of a major bleeding event decreased by 0.03 (p=0.02).
      CONCLUSION: Patients aged 65 years or older experience warfarin-related major
      bleeding events at a mean INR 1.1 units lower (95% confidence interval -1.9 to 
      0.27) than patients younger than 65 years. Older patients may require more
      aggressive management of overanticoagulation to minimize the risk of major
      bleeding.

PMID- 15162893
TI  - Sex-related differences in the pharmacokinetics of once-daily saquinavir soft
      gelatin capsules boosted with low-dose ritonavir in patients infected with human
      immunodeficiency virus type 1.
AB  - STUDY OBJECTIVES: To compare the steady-state pharmacokinetics and safety of
      saquinavir soft-gelatin capsules (SGC) plus low-dose ritonavir administered
      once/day in antiretroviral-naive adult patients infected with the human
      immunodeficiency virus type 1 (HIV-1) and to evaluate any sex-related
      differences. DESIGN: Single-center, open-label, pharmacokinetic study. SETTING:
      University-affiliated outpatient HIV clinic. PATIENTS: Six men and seven women
      with HIV-1. INTERVENTION: Each patient received saquinavir SGC 1600 mg and
      ritonavir 100 mg for a 14-day course of therapy. Nine serial blood samples during
      24 hours were collected on day 14 of therapy MEASUREMENTS AND MAIN RESULTS:
      Plasma saquinavir and ritonavir concentrations were measured by high-performance
      liquid chromatography. Standard noncompartmental methods were used to calculate
      the pharmacokinetic parameters. The unpaired Student t test was used for the
      statistical comparison of pharmacokinetic parameters between male and female
      patients. Once-daily saquinavir SGC plus ritonavir was generally well tolerated.
      Pharmacokinetic data from five men and five women were evaluable. The median
      saquinavir area under the concentration-time curve from 0-24 hours (AUC0-24) in
      the female patients (82,300 ng x hr/ml) was significantly (p=0.036) higher than
      that in the male patients (47,400 ng x hr/ml). This relationship remained
      significant for weight-adjusted saquinavir AUC0-24 values. Ritonavir's apparent
      oral clearance in the women was significantly (p=0.023) lower than that in the
      men. CONCLUSION: Significantly higher plasma concentrations of saquinavir were
      achieved in female compared with male HIV-infected patients receiving once-daily
      saquinavir SGC 1600 mg plus ritonavir 100 mg.

PMID- 15162896
TI  - Treatment of pain syndromes with venlafaxine.
AB  - Major depressive disorder (MDD) and anxiety disorders such as generalized anxiety
      disorder (GAD) are often accompanied by chronic painful symptoms. Examples of
      such symptoms are backache, headache, gastrointestinal pain, and joint pain. In
      addition, pain generally not associated with major depression or an anxiety
      disorder, such as peripheral neuropathic pain (e.g., diabetic neuropathy and
      postherpetic neuralgia), cancer pain, and fibromyalgia, can be challenging for
      primary care providers to treat. Antidepressants that block reuptake of both
      serotonin and norepinephrine, such as the tricyclic antidepressants (e.g.,
      amitriptyline), have been used to treat pain syndromes in patients with or
      without comorbid MDD or GAD. Venlafaxine, a serotonin and norepinephrine reuptake
      inhibitor, has been safe and effective in animal models, healthy human
      volunteers, and patients for treatment of various pain syndromes. The use of
      venlafaxine for treatment of pain associated with MDD or GAD, neuropathic pain,
      headache, fibromyalgia, and postmastectomy pain syndrome is reviewed. Currently,
      no antidepressants, including venlafaxine, are approved for the treatment of
      chronic pain syndromes. Additional randomized, controlled trials are necessary to
      fully elucidate the role of venlafaxine in the treatment of chronic pain.

PMID- 15162897
TI  - Food: an unrecognized source of loop diuretic resistance.
AB  - Food significantly affects the pharmacokinetics of oral loop diuretics in healthy
      individuals, but studies have not been performed in patients with edema. Because
      of this omission, food's effect on pharmacokinetics has been overlooked and may
      decrease the pharmacodynamic response in patients who rely on diuretics. Despite
      this potential interaction, reference manuals do not provide warnings about the
      effects of food on loop diuretic absorption. We reviewed the published human
      studies investigating the effects of food on loop diuretics. Peak plasma
      concentrations and urinary recovery were significantly decreased when taken with
      food, but only one study showed a corresponding decrease in total urine output,
      which is likely related to the diuretic threshold effect. These healthy subjects
      probably were always above the diuretic threshold under both fed and fasting
      conditions and thus could not augment their urine output. Based on these data in
      healthy subjects, the special implications for patients who routinely take
      diuretics are discussed. Therefore, food is more likely to have a clinical effect
      on the diuretic threshold given its effect in healthy subjects and the special
      considerations for patients with edema. Additional studies are needed to help
      answer these questions. Until such data are available, the most conservative,
      effective clinical approach is to administer oral loop diuretics without food.

PMID- 15162898
TI  - Migraine headache misconceptions: barriers to effective care.
AB  - Migraine headaches affect 12% of the adult population in the United States and
      cause a significant economic loss due to decreased workplace productivity
      Although interactions between pharmacists and individuals with headache are
      common, few pharmacists receive adequate training regarding migraine therapy. We
      refute several misconceptions that hinder effective care, such as that migraine
      is a vascular disease, triptans cause rampant cardiacrelated morbidity and even
      mortality, a best oral triptan exists, sinus and tension headaches are prevalent,
      and migraine is a minor economic problem. Our pathophysiologic understanding
      demonstrates that migraine is a neurologic process of the trigeminovascular
      system, of which vascular effects are secondary. This process can result in a
      myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus
      or tension headache. The last decade's experience with triptans in more than half
      a billion people worldwide reveals a benign adverse-effect profile, particularly
      when taken early in an attack. Published reports and real-world experiences
      illustrate that these drugs do not merit fears of triptan-induced cardiac
      consequences in appropriately selected individuals. Society's productivity loss
      due to migraine is measured in billions of dollars. Restoring a patient's ability
      to function normally is now recognized as the primary treatment goal, not merely
      relieving pain. Thus, the overreliance on "pain killer" drugs such as butalbital
      containing products and the continued underutilization of migraine-specific drugs
      need to be addressed. Opportunities exist for pharmacists and other health care
      providers to dispel continually propagated migraine misconceptions and
      familiarize themselves with advances in therapy. Such actions will benefit
      patients, the health care system, and society as a whole.

PMID- 15162899
TI  - A disease management protocol for outpatient perioperative bridge therapy with
      enoxaparin in patients requiring temporary interruption of long-term oral
      anticoagulation.
AB  - STUDY OBJECTIVE: Traditional perioperative bridge therapy for patients receiving
      long-term oral anticoagulation involves weight-adjusted intravenous
      unfractionated heparin (UFH) in the perioperative period during temporary
      discontinuation of the oral anticoagulant. We sought to determine whether an
      alternate strategy of outpatient-based perioperative disease management with low
      molecular-weight heparin (LMWH) as bridge therapy provides the potential for cost
      savings. DESIGN: Retrospective review of all clinic notes from an anticoagulation
      clinic. SETTING: An integrated, staff-model health maintenance organization.
      PATIENTS: Patients receiving long-term warfarin therapy from January 1998-March
      2002 who received perioperative bridge therapy with the LMWH enoxaparin 1 mg/kg
      twice/day subcutaneously MEASUREMENTS AND MAIN RESULTS: A total of 126 bridge
      therapy encounters in 84 patients receiving LMWH as perioperative bridge therapy
      were identified, with 48 of those encounters involving patients with at least one
      mechanical heart valve. A total of 1108 hospital bed days were saved. Based on
      1996 cost estimates, the total approximate cost savings for the 4.25 years of the
      outpatient bridge therapy program was dollars 903,020. No thrombotic events were
      reported. Three major hemorrhagic events that required discontinuation of LMWH
      were reported. CONCLUSION: Outpatient-based disease management protocols and the
      LMWH enoxaparin as bridge therapy during temporary discontinuation of warfarin
      for an elective surgical procedure resulted in cost savings of approximately
      dollars 212,475/year in an integrated health maintenance organization. In
      addition, this strategy appears both safe and effective.

PMID- 15162902
TI  - Cefazolin tolerance does not predict ceftriaxone hypersensitivity: unique side
      chains precipitate anaphylaxis.
AB  - A 48-year-old woman with a questionable history of an unspecified ceftriaxone
      allergy was treated with cefazolin for surgical antibiotic prophylaxis. After she
      tolerated cefazolin therapy for 4 days, the medical staff concluded that her
      allergy history was inaccurate, and she was treated with intravenous ceftriaxone
      for suspected nosocomial pneumonia. Approximately 10 minutes after the start of
      the infusion, the patient experienced anaphylaxis. Initial symptoms of oral
      angioedema and laryngopharyngeal constriction progressed to dyspnea, tachypnea,
      hypotension, and tachycardia, all of which quickly resolved after immediate
      treatment with hydrocortisone, diphenhydramine, and epinephrine. Skin testing
      with cefazolin, cefepime, and ceftriaxone revealed that the likely allergic
      determinant mediating the patient's hypersensitivity reaction was the unique
      ceftriaxone R2 side chain and not the beta-lactam ring, which initially was
      suspected by the physician. Immunoglobulin E-mediated hypersensitivity reactions
      to cephalosporins may occur due to antibody complexes with the beta-lactam ring
      or various cephalosporin side chains. Misconceptions regarding the nature of
      cephalosporin allergies complicate antibiotic selection for patients with
      questionable allergy histories and may lead to inappropriate drug reexposure and
      anaphylaxis. Detailed understanding of the antigenic determinants that mediate
      hypersensitivity reactions is essential for clinicians to avoid type 1 reactions
      in patients with a suspected allergy to cephalosporins.

PMID- 15162900
TI  - Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: case
      report and review of the literature.
AB  - Antithrombin deficiency is a hypercoagulable state that can increase the risk for
      thrombosis, especially in the presence of other procoagulant triggers.
      Unfractionated heparin and low-molecular-weight heparins may not provide
      effective anticoagulation since they require antithrombin for activity. Direct
      thrombin inhibitors, however, work independently of antithrombin. A 21-year-old
      man with a history of heavy alcohol consumption had thrombosis of the superior
      mesenteric vein. Infusion with unfractionated heparin was started, and despite
      repeated boluses and increases to 21 U/kg/hour, the maximum activated partial
      thromboplastin time reached was 39 seconds. The unfractionated heparin was
      discontinued, and the direct thrombin inhibitor argatroban was infused at rates
      of 0.4-0.5 microg/kg/minute. Over the course of several weeks, the patient had
      numerous operations to remove and repair necrotic bowel. When no further surgery
      was anticipated, warfarin therapy was started; the argatroban infusion was
      discontinued when the patient reached the therapeutic target international
      normalized ratio with warfarin. No recurrent thrombosis or major bleeding
      occurred. Direct thrombin inhibitors, such as argatroban, seem to be suitable
      alternatives for acute anticoagulation in patients with antithrombin deficiency.

PMID- 15162901
TI  - Clopidogrel-induced thrombotic thrombocytopenic purpura-hemolytic uremic syndrome
      after coronary artery stenting.
AB  - The antiplatelet drug clopidogrel has largely replaced ticlopidine, due to an
      association between ticlopidine and thrombotic thrombocytopenic purpura-hemolytic
      uremic syndrome (TTP-HUS). Clopidogrel at first was thought to be void of this
      potentially fatal adverse effect, but recent case reports have called that
      assumption into question. Even with proper treatment (plasma exchange), TTP-HUS
      can persist for weeks. Clinicians should be aware of this possible adverse effect
      because prompt therapy is imperative for patients' survival. Earlier reports of
      clopidogrel-related TTP-HUS have involved patients who had received at least 72
      hours of therapy. We describe a case of TTP-HUS in a patient who had received
      only a 300-mg loading dose of clopidogrel.

PMID- 15162903
TI  - Fatal acute encephalomyelitis after a single dose of intrathecal methotrexate.
AB  - A 40-year-old Hispanic man with acute lymphoblastic leukemia was treated with a
      single dose of intrathecal methotrexate 12 mg for prophylaxis against
      leptomeningeal spread of tumor. The day after methotrexate administration, the
      patient complained of severe back pain and urinary retention. The diagnosis of
      encephalomyelitis was made on day 3 after methotrexate administration, and by day
      6 mechanical ventilation was begun secondary to ascending paralysis. By day 8 the
      patient was comatose, with minimal signs of brain activity and little hope for
      recovery; on day 12 he died. Although neurotoxicity is a frequent complication of
      methotrexate therapy, fatal acute neurotoxicity is extremely uncommon, especially
      in adults. The mechanisms of methotrexate toxicity remain unclear, and no
      effective treatment exists to prevent its occurrence. This patient rapidly
      progressed from mild neurotoxicity to fatal encephalopathy after one dose of
      intrathecal methotrexate during his third cycle of chemotherapy. Clinicians
      should be aware of the signs and symptoms of neurotoxicity during treatment, as
      well as predisposing factors that put patients receiving methotrexate at risk for
      neurotoxic effects.

PMID- 15162904
TI  - An individual perspective on the pharmacy education scope of practice disconnect.

PMID- 15162905
TI  - Pharmacy education redux.

PMID- 15162906
TI  - Pharmacy education: back to the basics?--An alternative viewpoint.

PMID- 15162907
TI  - The future of pharmacy education: back to which basics?

PMID- 15162908
TI  - Pharmacy education: beyond the basics.

PMID- 15162909
TI  - Acetaminophen intoxication and length of treatment: how long is long enough?--A
      comment.

PMID- 15162910
TI  - Elevations in serum creatinine concentration: concerning or reassuring?
AB  - The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin
      receptor blockers (ARBs) has significantly reduced morbidity and mortality across
      the continuum of vascular disease. The utilization of these agents, however,
      remains suboptimal. The drugs are not prescribed in many patients because of
      concerns regarding their effects on renal function. Despite overwhelming evidence
      in favor of renoprotection, it is not uncommon for the glomerular filtration rate
      (GFR) to decrease shortly after starting treatment with an ACE inhibitor or ARB.
      This response is functional in nature and should be expected based on renal
      physiology and its dependence on the renin-angiotensin system to maintain GFR.
      Unfortunately, this phenomenon sometimes is viewed as an adverse effect or an
      indicator of underlying pathology. Although somewhat counterintuitive, early
      elevations in serum creatinine concentration are associated with improved long
      term renal outcomes in patients with renal insufficiency and thus support, rather
      than condemn, continued treatment. Clinicians should be aware of the physiologic
      course associated with blockade of the renin-angiotensin system so that these
      agents will not be withheld unnecessarily.

PMID- 15162911
TI  - 3D topographic study of the diode laser evoked potentials (LEPs) to painful
      stimulation of the trigeminal sensory area.
AB  - A diode laser attached with an optic fiber is flexible and adequate for painful
      cutaneous stimulation. The brain potentials elicited by diode laser stimulation
      reflect activation of thin-myelinated afferent fibers. This study examined the
      use of diode laser evoked potentials (LEPs) elicited from the left/right
      ophthalmic and maxillary branch of the trigeminal nerve. Twelve males (age: 26.3
      +/- 4.5) participated in this study. A 20W diode laser (980 nm wavelength, 0.5 mm
      spot diameter) was used for stimulation. The stimulus duration was 250 ms, and
      inter-stimulus interval was 5 sec. The stimulus intensity was tailored to each
      individual eliciting mild pinprick pain. Fifty stimuli were delivered to each of
      the four stimulation sites. Atotal of 32 channels EEG (-1024 ms to 2048 ms) was
      recorded. The grand mean averages were evaluated using 3D topographic brain maps.
      Repeated measure ANOVA was used for statistical comparisons. Ten out of the 12
      subjects resulted in a vertex component with major activations described as a
      negativity (-6.15 to -7.52 microV) peaking around 370 ms and a positivity (14.22
      to 16.29 microV) peaking around 500 ms. This vertex potential reflected
      activation of the thin A-delta fiber innervating thermal and nociceptive
      receptors in the face. This vertex potential to diode laser stimulation may be
      applicable in clinical studies in patients with neurological affections of the
      trigeminal nerves or nucleus e.g. before and after surgery. The diode laser may
      be very useful for clinical neurophysiological purposes due to its applicability
      and user-friendly function.

PMID- 15162912
TI  - Commonalities and differences among vectorized beamformers in electromagnetic
      source imaging.
AB  - A number of beamformers have been introduced to localize neuronal activity using
      magnetoencephalography (MEG) and electroencephalography (EEG). However, currently
      available information about the major aspects of existing beamformers is
      incomplete. In the present study, detailed analyses are performed to study the
      commonalities and differences among vectorized versions of existing beamformers
      in both theory and practice. In addition, a novel beamformer based on higher
      order covariance analysis is introduced. Theoretical formulas are provided on all
      major aspects of each beamformer; to examine their performance, computer
      simulations with different levels of correlation and signal-to-noise ratio are
      studied. Then, an empirical data set of human MEG median-nerve responses with a
      large number of neuronal generators is analyzed using the different beamformers.
      The results show substantial differences among existing MEG/EEG beamformers in
      their ways of describing the spatial map of neuronal activity. Differences in
      performance are observed among existing beamformers in terms of their spatial
      resolution, false-positive background activity, and robustness to highly
      correlated signals. Superior performance is obtained using our novel beamformer
      with higher-order covariance analysis in simulated data. Excellent agreement is
      also found between the results of our beamformer and the known neurophysiology of
      the median-nerve MEG response.

PMID- 15162913
TI  - Discriminating the cortical representation sites of tongue and up movement by
      functional MRI.
AB  - PURPOSE: The purpose of this study was to investigate the possibility to
      discriminate the representation sites of lip and tongue movement in the primary
      motor cortex (PMC). In contrast to preceding studies this research was
      particularly focused on single subject analysis. PROCEDURES: Six healthy right
      handed volunteers underwent functional magnetic resonance imaging (fMRI) by means
      of a 1.5 tesla scanner. Using a block design the subjects had to perform two
      different motor tasks: horizontal tongue movement and symmetrical lip pursing. To
      ensure that only the functional selective cortical representations for each
      particular motor task were determined, the approach of contrasting both motor
      paradigms was followed during data analysis. PRINCIPLE RESULTS: Selective cortex
      activations for both motor tasks were detectable in the motor strips and could be
      spatially discriminated for the whole group and for the majority of the single
      subjects in both hemispheres. Furthermore, expanded regions responsive to both
      motor tasks were found bilaterally. CONCLUSIONS: The individually proven
      possibility to differentiate the cortical representation sites of tongue and lip
      movements opens the chance to monitor therapeutic cortical effects after neuro
      reconstructive surgery, e. g. hypoglossal-facial nerve anastomosis (HFA).

PMID- 15162914
TI  - Topographic analysis of painful laser and sural nerve electrical evoked
      potentials.
AB  - A quantitative scalp topographic pattern analysis was used to compare evoked
      potentials elicited by painful laser (LEP) and electrical stimulation of the
      sural nerve (snSEP) in 22 healthy adults. The snSEP and LEP were separated into
      stable periods (consecutive time points having the same topographic pattern). The
      topographic pattern is dependent upon the number, location, orientation and
      relative magnitudes of the brain areas active at that time (source
      configuration). Demonstrating that 2 topographies have the same topographic
      pattern, therefore, provides evidence that they are generated by the same source
      configuration. The snSEP SP2/3 and SP3 stable periods have similar topographic
      features as the stable periods encompassing the LEP N1 and N2 peaks. However, the
      quantitative scalp topographic analysis demonstrated that the snSEP SP2/3 and SP3
      have a much larger fronto-central negativity. Our earlier work suggests this
      difference might be due to the sural nerve electrical stimulus evoking a more
      robust pain-evoked response from the anterior cingulate cortex than the laser.
      The snSEP SP6 topographic pattern was essentially the same as the LEP P2 peak.
      This finding plus the results of our earlier work demonstrate that SP6 is the
      snSEP analogue of the LEP P2 peak. These findings have important implications for
      the choice of evoking stimulus in investigations of pain processing in humans.
      For example, the sural nerve electrical stimulus will be preferred over the laser
      in studies of the anterior cingulate's role in cognitive processes related to
      pain, such as orienting attention, and/or in studies involving cognitive tasks
      that require the presentation of a large number of painful stimuli. The LEP N1
      and N2 peaks, on the other hand, will be preferred in studies of the parietal
      operculum's role in pain sensation.

PMID- 15162915
TI  - Binding and measuring natural rubber latex proteins on glove powder.
AB  - Cornstarch used as a donning powder on natural rubber latex (NRL) gloves adsorbs
      NRL proteins. During glove use, powder-carried proteins can be aerosolized and
      can cause allergic reactions in NRL sensitized individuals. The amount of NRL
      proteins bound to glove powder and its relative relationship to the total amount
      of proteins on the glove has not been studied, due to the difficulty in measuring
      proteins on powder. Using the ELISA inhibition assay for NRL proteins [Standard
      test method for the immunological measurement of antigenic protein in natural
      rubber and its products. In: The Annual Book of ASTM Standards; ASTM: West
      Conshohocken, PA, 2000; ASTM D 64-0] we have investigated possible protocol
      modifications in order to include measurement of proteins bound to glove powder,
      as well as the water-extractable glove proteins. Possible interference of the
      starch itself was evaluated by adding clean cornstarch to the assay. No
      significant interference was observed with powder concentrations below 5 mg/mL.
      We analyzed 19 extracts of powdered surgical and examination gloves before and
      after removal of the particulate component. Comparison of NRL glove extracts
      with, and without, the cornstarch powder fraction indicated significant
      variations in the ratios of powder-bound protein and corresponding water
      extractable protein. The ratios did not appear to correlate with either the total
      protein on the glove, the glove weight, or the total amount of powder on the
      glove. However, when virgin glove powders were exposed to NRL proteins, binding
      was proportional to the protein concentration in the suspension. Temperature in
      the range from 4 degrees C to 37 degrees C, did not affect binding intensity,
      while a higher pH resulted in a higher level of protein associated with, or bound
      to, the starch. The major differences in the propensity for NRL protein binding
      were observed among different glove powders. The data indicate that the amount of
      protein that binds to glove powder does not depend only on the initial protein
      levels in the raw NRL. More likely, other physical or chemical factors introduced
      during the manufacturing process, as well as the properties of the donning powder
      itself, may influence protein binding. Moreover, we demonstrated that the ELISA
      inhibition assay could be successfully modified for quantitation of proteins
      adsorbed on the glove powder, together with water-extractable proteins.

PMID- 15162916
TI  - Comparative bioavailability study of two tablet formulations of digoxin.
AB  - This investigation was carried out to evaluate the bioavailability of the generic
      product of digoxin 0.25 mg (cardixin) relative to a reference product, lanoxin
      (0.25 mg) tablets. The two formulations were found to be similar in in vitro
      assay (dissolution) as stipulated by USP XXIII. The comparison is carried out on
      12 healthy male volunteers, who received a single dose (0.25 mg) of cardixin
      (product A) lanoxin (product B) as a reference product orally in the fasting
      state, in a randomized balanced two-way crossover design. After dosing, serial
      blood samples were collected for a period of 12 hr. Plasma samples were analyzed
      for digoxin by a sensitive and validated enzyme immunoassay method (ELISA). The
      maximum plasma concentration curve, up to the last measurable concentration
      (AUC(0-24)), was analyzed under the assumption of a multiplicative model. The
      time to maximum concentration (Tmax) was analyzed, assuming an additive model.
      The parametric confidence intervals (90%) of the mean values of the
      pharmacokinetic characteristics (AUC(0-12) and Cmax) for A:B ratio were, in each
      case, well within the bioequivalence acceptable range of 80-125%.

PMID- 15162917
TI  - Development and validation of an ELISA for hemoglobin-A2: a novel method for beta
      thalassemia screening in developing countries.
AB  - Hemoglobin-A2 (HbA2) measurement in human hemolysates has great significance,
      since its level can indicate beta-thalassemia carrier status in otherwise healthy
      individuals. An ELISA for HbA2 using antiserum monospecific to the delta chain of
      HbA2 and affinity purified antirabbit gamma globulins (ARGG) conjugated to
      horseradish peroxidase (HRP) have been developed. The monospecific antiserum used
      does not cross react with other hemoglobins. Hemolysates from volunteers are used
      for measurement of HbA2. In a limited trial for beta-thalassemia carrier
      screening (n = 350), the results obtained with the developed ELISA are comparable
      with those obtained with a micro-column chromatography method (r > or = 0.89).
      The developed ELISA is simple, accurate, precise, inexpensive, and several
      samples can be processed simultaneously with ease, making this system a suitable
      candidate for transforming into a user friendly kit.

PMID- 15162918
TI  - Screening for epitope specificity directly on culture supernatants in the early
      phase of monoclonal antibody production by an ELISA with biotin-labeled antigen.
AB  - This report describes an assay for comparison of epitope specificity in groups of
      monoclonal antibodies against a given antigen. The only prerequisite is the
      biotin-labeled antigen. One of the monoclonal antibodies is captured onto a
      plastic surface via a rabbit anti-mouse Ig, and the other preincubated with
      biotinylated antigen. When the two antibodies react with the same epitope
      subsequent binding of the biotin-labeled antigen is abolished (inhibition). In
      the cases where no inhibition was observed, the two antibodies were considered to
      react with distinct, independent epitopes. The obvious advantages using this
      assay, are that it can be performed directly on culture supernatants in the early
      phase of monoclonal antibody production, and also works for antigens with
      repetitive epitopes. Moreover, the bonus effect, i.e., a signal in excess of the
      reference signal when sets of monoclonal antibodies with different epitope
      specificity are compared, gives a relative measure of affinity.

PMID- 15162919
TI  - Detection of the soluble heat shock protein 27 (hsp27) in human serum by an
      ELISA.
AB  - Increased levels of autoantibodies against heat shock protein 27 (hsp27) in
      patients with breast, ovarian, or endometrial cancer strongly suggest the
      presence and increased levels of hsp27 in their circulation. Therefore, we have
      developed a sensitive and reproducible ELISA for quantification of soluble hsp27
      levels in biological fluid such as serum. The assay is highly specific for hsp27.
      The limit of detection of the ELISA is about 0.5 ng/mL. The mean intra- and inter
      coefficients of variation were 7.45 and 8.18, respectively. The recovery of the
      recombinant protein was nearly 100%. The assay could detect soluble hsp27 levels
      in normal human serum when the level was >0.5 ng/mL. Out of 28 serum samples we
      tested, 10 samples were not detected for any hsp27 level in our ELISA. However,
      hsp27 levels could be detected in the other 18 samples. The median serum hsp27
      level was 3.27 ng/mL when all the 28 normal control samples were included. Low
      levels of hsp27 in normal human serum may be useful to distinguish the hsp27
      levels in breast or other cancer patients during the progression of the disease.
      Therefore, the use of hsp27 ELISA could be extremely useful in evaluating the
      role of soluble hsp27 in breast or other cancers.

PMID- 15162920
TI  - Rough lipopolysaccharide of Brucella abortus RB51 as a common antigen for
      serological detection of B. ovis, B. canis, and B. abortus RB51 exposure using
      indirect enzyme immunoassay and fluorescence polarization assay.
AB  - Rough lipopolysaccharide (RLPS) antigens were prepared from cultures of Brucella
      abortus RB51, B. ovis, and B. canis. The preparations were standardized by weight
      and tested with sera from cattle immunized with B. abortus RB51, sheep infected
      with B. ovis, and dogs infected with B. canis. Populations of unexposed animals
      of each species were also tested. The tests used were the indirect enzyme
      immunoassay (IELISA) using RLPS and the fluorescence polarization assay (FPA)
      using RLPS core fractions, labeled with fluorescein isothiocyanate. The IELISA
      using B. abortus RB51 RLPS antigen resulted in sensitivity and specificity values
      of 94.8% and 97.3%, respectively, when testing bovine sera, 98.5% and 97.8% when
      testing ovine sera, and 95.8% and 100% when testing dog sera. The IELISA using B.
      ovis RLPS antigen gave sensitivity and specificity values of 80.5% and 91.7%,
      respectively with bovine sera, 98.9% and 93.8% with sheep sera, and 70.8% and
      79.8% with dog sera. The IELISA using B. canis RLPS antigen resulted in
      sensitivity and specificity values of 97.0% and 97.4%, respectively, with bovine
      sera, 96.2% and 96.3% with sheep sera, and 95.8% and 98.8% with dog sera.
      Labeling RLPS core from B. ovis and B. canis with fluorescein was not successful.
      B. abortus RB51 core labeled with fluorescein resulted in sensitivity and
      specificity values of 93.5% and 99.8%, respectively, with bovine sera and 78.1%
      and 99.0% with sheep sera. It was not possible to test the dog sera in the FPA.

PMID- 15162921
TI  - Determination of (+)-3,3',5-triiodo-L-thyronine (L-T3) from serum using a
      sequential injection analysis/immunosensor system.
AB  - A sequential injection analysis/immunosensor system is proposed for the analysis
      of T3 in serum with a rate of 75 samples/hr. The immunosensor design is based on
      the physical immobilization of anti-T3 in carbon paste. The working concentration
      range of the immunosensor in a sequential injection analysis system is between
      3.4 and 340 ng/mL with a limit of detection of 2.19 ng/mL. The system is very
      reliable and very easy to design and operate.

PMID- 15162923
TI  - Effect of cardiopulmonary bypass on leukocyte activation: changes in membrane
      bound elastase on neutrophils.
AB  - BACKGROUND: Neutrophil elastase is known to be released from the activated
      leukocytes as a result of cardiopulmonary bypass (CPB). However, its biological
      effect on organ injury is questionable because it is quickly bound by natural
      proteinase inhibitors (PIs). Recently, membrane-bound elastase (MBE) was found to
      be able to resist the PIs' process and, thus, is biologically more active. This
      paper studies the effect of CPB on the kinetic change of MBE and its possible
      link to postoperative inflammation and organ function. METHOD: Ten consecutive
      patients undergoing elective coronary artery bypass grafting (CABG) surgery with
      CPB were recruited into the study. Blood samples were taken before sternotomy,
      after aortic declamping, at the end of CPB, three and six hours after CPB and on
      the first postoperative day. MBE was determined by substrate assay from isolated
      neutrophils. Inflammation and organ function markers methods. RESULTS: MBE
      slightly increased after aortic declamping, while it significantly increased and
      reached its peak at the end of CPB; it returned to its preoperative level on the
      first postoperative day. In contrast to lung sequestration of neutrophils, there
      was no transpulmonary gradient of MBE between left and right atria after aortic
      declamping. Neither MBE nor total MBE activity was positively correlated with
      postoperative inflammation markers such as blood lactate and C-reactive protein
      and organ function markers such as creatine phosphokinase and alanine
      aminotransferase. CONCLUSIONS: CPB induces increased MBE expression on
      neutrophils with its peak at the end of CPB. Lack of association between
      neutrophil MBE and clinical markers suggests that multiple systems might be
      involved in the post-CPB inflammatory reaction and organ dysfunction.

PMID- 15162922
TI  - Highly positive intraoperative fluid balance during cardiac surgery is associated
      with adverse outcome.
AB  - Hemodilution and increase in capillary permeability occurring with
      cardiopulmonary bypass (CPB) impose a risk for tissue edema and blood transfusion
      that may result in an increased complication rate after coronary artery bypass
      grafting (CABG). Of the 1280 consecutive patients undergoing isolated on-pump
      CABG, total fluid balance at the end of the operation was less than or equal to
      500 mL in 1155 (Group 1) and more than 500 mL in 125 (Group 2). During CPB, blood
      was added to the reservoir only when the hematocrit fell to 17% or less and
      crystalloid solution only when the pump flow index fell below 2.0 L/min/m2.
      Anesthetic, surgical, and postoperative management and diagnoses were the same in
      all patients, and a single surgical and anesthesia team performed all operations.
      No patient was excluded from the study. RESULTS: Hypertension, diabetes, chronic
      obstructive pulmonary disease, New York Heart Association (NYHA) Class III-IV,
      use of angiotensin converting enzyme (ACE) inhibitors, chronic renal failure, and
      female gender were the significant preoperative risk factors for increased volume
      replacement during CPB. The groups were similar in body mass index, preoperative
      hematocrit values, total fluid balance in the intensive care unit (ICU), and
      total chest tube output. However, red blood cells' transfusion rate, readmission
      rate to the ICU and length of hospital stay were significantly higher in Group 2
      patients. Multiple logistic regression revealed that age > 70 years (p < 0.001,
      Odds Ratio (OR): 2, 95% CI: 1.4-2.8), and total fluid balance > 500 mL at the end
      of the operation (p < 0.01, OR: 2.2, 95% CI: 1.5-3.2) were the predictors of
      increased length of stay. For transfusion of red blood cells, age > 70 years (p <
      0.0001, OR: 2.3, 95% CI: 1.6-3.3), and total fluid balance > 500 mL at the end of
      the operation (p < 0.001, OR: 2, 95% CI: 1.3-2.9) were the only significant risk
      factors. This study suggests that intraoperative volume overload increases blood
      transfusion and length of hospital stay in patients undergoing CABG.

PMID- 15162925
TI  - Pump-induced haemolysis: a comparison of short-term ventricular assist devices.
AB  - Centrifugal pumps are superior to roller pumps for extended support durations in
      terms of pump-induced haemolysis. In this study, we evaluated the commonly used
      Biomedicus BP 50 and compared it with the Jostra Rotaflow and a standard roller
      pump in an in vitro test circuit. Each circuit was run for a six-day period and
      repeated five times. Plasma haemoglobin values showed the roller pump to become
      more haemolytic than the Biomedicus (p = 0.022) and the Rotaflow. A statistically
      significant difference between the Biomedicus and the Rotaflow was observed on
      day six of the trial (p = 0.016), with the Rotaflow showing lower levels of
      haemolysis than the Biomedicus. These results support the use of the new
      generation centrifugal pump, the Rotaflow, as a suitable device for short-term
      ventricular assist.

PMID- 15162924
TI  - The cerebroprotective effects of pentoxifylline and aprotinin during
      cardiopulmonary bypass in dogs.
AB  - OBJECTIVE: The purpose of this study was to investigate the cerebroprotective
      effects of pentoxifylline (PNX) and aprotinin in dogs using cardiopulmonary
      bypass (CPB). MATERIALS AND METHODS: Eighteen clinically healthy dogs were
      divided into three groups: Group 1 (control, n = 6), Group 2 (PNX, n = 6), and
      Group 3 (aprotinin, n = 6). PNX was administered at a dose of 300 mg/day in Group
      2 three days before the operation and during the operation. Half a million IU
      aprotinin were added to the prime solution and 500,000 IU were transfused via a
      central venous jugular catheter preoperatively in Group 3. Blood samples were
      taken from the central jugular vein before and after CPB and interleukin-6 (IL
      6), tumor necrosis factor-alpha (TNF-alpha), and S100beta protein were measured.
      Gliosis was investigated histopathologically in cerebral cortex biopsy samples
      under light microscopy. RESULTS: The preoperative results of IL-6, TNF-alpha, and
      S100beta protein values were found to be significantly higher (p < 0.001) when
      compared with postoperative values. This significant difference was observed in
      the same parameters between Groups 1 and 2, and 1 and 3 (p < 0.001). There was no
      significant difference between Groups 2 and 3. Comparison between pre- and
      postoperative levels of IL-6 and TNF-alpha for Group 2 and Group 3 revealed
      statistically significant differences (p < 0.001), whereas S100beta protein
      levels did not. Histopathological examinations showed significant differences
      between the control group and PNX and aprotinin, and between aprotinin and PNX
      groups (p < 0.001). CONCLUSION: PNX and aprotinin might be useful in order to
      reduce postoperative cerebral damage in patients undergoing cardiac surgery with
      CPB.

PMID- 15162926
TI  - In vitro assessment of the vacuum-assisted venous drainage (VAVD) system: risks
      and benefits.
AB  - The vacuum-assisted venous drainage (VAVD) technique has been introduced with the
      utilization of small-bore venous cannulae to facilitate minimally invasive
      cardiac surgery and it has found widespread use for traditional surgical
      approaches. Although this technique was devised to increase venous return, it may
      cause a reduction of blood flow through a negative pressure effect on the raceway
      tubing. In this study, the potential of this system to increase the venous
      drainage was evaluated in vitro together with the measurements of delivered blood
      flow. The VAVD has been tested in association with normal gravitational drainage
      or as a substitute for gravitational drainage. The flow was calculated by
      multiplying the pump rate by the stroke volume and it was simultaneously measured
      by a magnetic flowmeter. A steady state maximal flow was defined as the flow that
      could maintain a constant level of fluid in the graduated canister used to act as
      the patient. Based on our results, the VAVD can increase venous drainage by as
      much as 50% above baseline levels. However, delivered blood flow may be
      overestimated, particularly when negative pressure values > 60 mmHg are employed.
      A 100 mmHg negative pressure may produce an overestimate of blood flow as great
      as 54% of the measured flow.

PMID- 15162927
TI  - Highest core temperature during cardiopulmonary bypass and rate of mediastinitis.
AB  - Temperature control during cardiopulmonary bypass (CPB) may be related to rates
      of bacterial infection. We assessed the relationship between highest core
      temperature during CPB and rates of mediastinitis in 6955 consecutive isolated
      coronary artery bypass graft (CABG) procedures in northern New England. The
      overall rate of mediastinitis was 1.1%. The association between highest core
      temperature and mediastinitis was different for diabetics than for nondiabetics.
      A multivariate model showed that there was a significant interaction between
      diabetes and temperature in their association with mediastinitis (p=0.015).
      Diabetic patients showed higher rates of mediastinitis as highest core
      temperature increased, from 0.7% in the < or = 37 degrees C group to 3.3% in the
      > or = 38 degrees C group (p(trend) = 0.002). Adjusted rates were similar.
      Nondiabetic patients did not show this trend (p(trend) = 0.998). Among diabetic
      patients, a peak core body temperature > 37.9 degrees C during CPB is a
      significant risk factor for development of mediastinitis. Avoidance of higher
      temperatures during CPB may lower the risk of mediastinitis for diabetic patients
      undergoing CABG surgery.

PMID- 15162928
TI  - Inflammatory response in an immunosuppressed patient with Wegener's
      granulomatosis.
AB  - BACKGROUND: The use of cardiopulmonary bypass (CPB) triggers a systemic
      inflammatory response (IR), but it is not known if a similar response occurs in
      an immunosuppressed patient with autoimmune disease. METHODS AND RESULTS:
      Observational study in a 56-year-old man receiving immunosuppressive therapy for
      Wegener's granulomatosis (WG) who underwent aortic valve replacement on CPB. The
      following markers for IR were studied in the perioperative period: C3a, C5a,
      neutrophil elastase (NE), interleukin eight (IL-8), white cell count (WCC) and C
      reactive protein (CRP). Results were compared with published literature on the IR
      in patients undergoing coronary revascularisation with and without the use of
      CPB. All inflammatory markers increased in the perioperative period. The
      intensity of IR was markedly reduced compared to published literature for
      patients undergoing coronary revascularisation on CPB and the temporal patients
      and extend resembled that for off-pump. CONCLUSION: In a patient with WG on
      immunosuppressive therapy the CPB-related IR is reduced.

PMID- 15162929
TI  - Dural sinus thrombosis after cardiopulmonary bypass.
AB  - Cerebral venous thrombosis in various clinical conditions, such as congenital
      heart disease (CHD) and hypercoagulable states, have been recognized previously.
      However, dural sinus thrombosis in a pediatric patient with Antiphospholipid
      Syndrome (APLS) after the repair of a ventricular septal defect (VSD) has not
      been reported yet. A child who underwent an operation for the surgical repair of
      VSD under cardiopulmonary bypass (CPB) developed a stroke after the procedure. A
      cranial computer tomography (CT) scan of the patient showed dural sinus
      thrombosis and severe cerebral edema. APLS and CPB were thought to be the only
      risk factors of dural sinus thrombosis. This observation warrants attention and
      screening should be taken into consideration in patients with APLS who carry a
      higher risk for dural sinus thrombosis after CPB.

PMID- 15162930
TI  - Effects of a computer-based intervention program on the communicative functions
      of children with autism.
AB  - This study investigated the use of computer-based intervention for enhancing
      communication functions of children with autism. The software program was
      developed based on daily life activities in the areas of play, food, and hygiene.
      The following variables were investigated: delayed echolalia, immediate
      echolalia, irrelevant speech, relevant speech, and communicative initiations.
      Multiple-baseline design across settings was used to examine the effects of the
      exposure of five children with autism to activities in a structured and
      controlled simulated environment on the communication manifested in their natural
      environment. Results indicated that after exposure to the simulations, all
      children produced fewer sentences with delayed and irrelevant speech. Most of the
      children engaged in fewer sentences involving immediate echolalia and increased
      the number of communication intentions and the amount of relevant speech they
      produced. Results indicated that after practicing in a controlled and structured
      setting that provided the children with opportunities to interact in play, food,
      and hygiene activities, the children were able to transfer their knowledge to the
      natural classroom environment. Implications and future research directions are
      discussed.

PMID- 15162931
TI  - Exploration of strategies for facilitating the reading comprehension of high
      functioning students with autism spectrum disorders.
AB  - Many students with autism spectrum disorders show good decoding combined with
      poor comprehension. Twenty adolescent students with autism spectrum disorders
      participated in a study concerning the effects of three kinds of facilitation on
      reading comprehension. In a within-subjects design, each students read passages
      under four conditions: answering prereading questions, completing cloze sentences
      embedded in the text, resolving anaphora by identifying relevant antecedents, and
      control (reading only). A repeated measures analysis of variance indicated that
      conditions differed significantly in their effects on reading comprehension. Post
      hoc contrasts showed that the effects of anaphoric cuing were statistically
      significant and medium in size; the effects of prereading questions and cloze
      completion were small and not statistically significant. Instructional
      implications for text preparation, remedial instruction, and the design of
      educational software are discussed.

PMID- 15162932
TI  - Interrelationship between Autism Diagnostic Observation Schedule-Generic (ADOS
      G), Autism Diagnostic Interview-Revised (ADI-R), and the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV-TR) classification in children and
      adolescents with mental retardation.
AB  - The interrelationship between the Autism Diagnostic Interview-Revised (ADI-R),
      Autism Diagnostic Observation Schedule-Generic (ADOS-G) and clinical
      classification was studied in 184 children and adolescents with Mental
      Retardation (MR). The agreement between the ADI-R and ADOS-G was fair, with a
      substantial difference between younger and older children (5-8 vs. 8+ years).
      Compared with the Diagnostic and Statistical Manual of Mental Disorders-IV-TR
      (DSM-IV-TR) classification of Autistic Disorder (AD) and Pervasive Developmental
      Disorder (PDD), both instruments measure AD or PDD validly and reliably. Even in
      low-functioning children the interrelationship between the instruments and the
      clinical classification was satisfactory. The combination of ADI-R and ADOS-G
      identifies AD or PDD, as described in the DSM-IV-TR, most appropriately. Both
      instruments seem to be of great value in the diagnostic process of PDD in
      children and adolescents with MR.

PMID- 15162933
TI  - Performance on Cambridge Neuropsychological Test Automated Battery subtests
      sensitive to frontal lobe function in people with autistic disorder: evidence
      from the Collaborative Programs of Excellence in Autism network.
AB  - Recent structural and functional imaging work, as well as neuropathology and
      neuropsychology studies, provide strong empirical support for the involvement of
      frontal cortex in autism. The Cambridge Neuropsychological Test Automated Battery
      (CANTAB) is a computer-administered set of neuropsychological tests developed to
      examine specific components of cognition. Previous studies document the role of
      frontal cortex in performance of two CANTAB subtests: the Stockings of Cambridge,
      a planning task, and the Intradimensional/Extradimensional Shift task, a measure
      of cognitive set shifting. To examine the integrity of frontal functions, these
      subtests were administered to 79 participants with autism and 70 typical controls
      recruited from seven universities who are part of the Collaborative Programs of
      Excellence in Autism network. The two groups were matched on age, sex, and full
      scale IQ. Significant group differences were found in performance on both
      subtests, with the autism group showing deficits in planning efficiency and
      extradimensional shifting relative to controls. Deficits were found in both lower
      and higher-IQ individuals with autism across the age range of 6 to 47 years.
      Impairment on the CANTAB executive function subtests did not predict autism
      severity or specific autism symptoms (as measured by the ADI-R and ADOS), but it
      was correlated with adaptive behavior. If these CANTAB subtests do indeed measure
      prefrontal function, as suggested by previous research with animals and lesion
      patients, this adds to the accumulating evidence of frontal involvement in autism
      and indicates that this brain region should remain an active area of
      investigation.

PMID- 15162934
TI  - Comparing rates of psychiatric and behavior disorders in adolescents and young
      adults with severe intellectual disability with and without autism.
AB  - Eight males and four females with an Autism Diagnostic Interview-Revised (ADI-R)
      diagnosis of autism (mean age of 16.3 years) and severe intellectual disability
      (IQ < 40) were individually matched to controls on the basis of chronological
      age, gender, and nonverbal IQ. The dependent measure was the Diagnostic
      Assessment for the Severely Handicapped-II, which is used to screen for
      psychiatric and behavior disorders in lower-functioning individuals. Participants
      with autism showed significantly greater disturbances as measured by the
      Diagnostic Assessment for the Severely Handicapped-II total score and seven of 13
      subscales. They also averaged 5.25 clinically significant disturbances compared
      with 1.25 disturbances for participants without autism. Specific vulnerabilities
      to anxiety, mood, sleep, organic syndromes, and stereotypies/ tics were found in
      the participants with comorbid autism.

PMID- 15162936
TI  - Counterfactual and mental state reasoning in children with autism.
AB  - The contributions of counterfactual conditional reasoning (CCR), belief
      understanding, and inferential reasoning to the performance of children with
      autism (CWA) on standard false belief tasks were investigated. To assess the
      roles of these three factors, we compared the performance of CWA on physical
      state CCR tasks (which do not require either an understanding of belief or
      inferential reasoning); on Wellman and Bartsch's (1988) nonstandard tests of
      false belief (which require an understanding of belief, but not CCR or
      inferential reasoning), and on standard tests of false belief tasks. The CWA were
      impaired relative to controls on the physical-state CCR and standard false-belief
      tasks, but not on the nonstandard false-belief tasks, and the CWA's performance
      on the physical-state CCR and standard false-belief tasks correlated highly, even
      when the effects of verbal ability were partialled out. Finally, the CWA's
      performance on standard false-belief tasks was more impaired than their
      performance on the physical-state CCR tasks. We concluded that impaired
      performance on standard false-belief tasks in autism is associated with defective
      competence in CCR (or some of its component skills), plus defective competence in
      inferential reasoning and possibly generativity, but that impaired performance is
      not caused by an inadequate understanding of belief. The results are discussed in
      relation to other hypotheses concerning the cause or causes of impaired
      performance on standard false-belief tasks in children with autism.

PMID- 15162935
TI  - The empathy quotient: an investigation of adults with Asperger syndrome or high
      functioning autism, and normal sex differences.
AB  - Empathy is an essential part of normal social functioning, yet there are precious
      few instruments for measuring individual differences in this domain. In this
      article we review psychological theories of empathy and its measurement. Previous
      instruments that purport to measure this have not always focused purely on
      empathy. We report a new self-report questionnaire, the Empathy Quotient (EQ),
      for use with adults of normal intelligence. It contains 40 empathy items and 20
      filler/control items. On each empathy item a person can score 2, 1, or 0, so the
      EQ has a maximum score of 80 and a minimum of zero. In Study 1 we employed the EQ
      with n = 90 adults (65 males, 25 females) with Asperger Syndrome (AS) or high
      functioning autism (HFA), who are reported clinically to have difficulties in
      empathy. The adults with AS/HFA scored significantly lower on the EQ than n = 90
      (65 males, 25 females) age-matched controls. Of the adults with AS/HFA, 81%
      scored equal to or fewer than 30 points out of 80, compared with only 12% of
      controls. In Study 2 we carried out a study of n = 197 adults from a general
      population, to test for previously reported sex differences (female superiority)
      in empathy. This confirmed that women scored significantly higher than men. The
      EQ reveals both a sex difference in empathy in the general population and an
      empathy deficit in AS/HFA.

PMID- 15162937
TI  - Self-organization of an artificial neural network subjected to attention shift
      impairments and familiarity preference, characteristics studied in autism.
AB  - Autism is a developmental disorder with possibly multiple pathophysiologies. It
      has been theorized that cortical feature maps in individuals with autism are
      inadequate for forming abstract codes and representations. Cortical feature maps
      make it possible to classify stimuli, such as phonemes of speech, disregarding
      incidental detail. Hierarchies of such maps are instrumental in creating abstract
      codes and representations of objects and events. Self-Organizing Maps (SOMs) are
      artificial neural networks that offer insights into the development of cortical
      feature maps. Attentional impairment is prevalent in autism, but whether it is
      caused by attention-shift impairment or strong familiarity preference or negative
      response to novelty is a matter of debate. We model attention shift during self
      organization by presenting a SOM with stimuli from two sources in four different
      modes, namely, novelty seeking (regarded as normal learning), attention-shift
      impairment (shifts are made with a low probability), familiarity preference
      (shifts made with a lower probability to the source that is the less familiar to
      the SOM of the two sources), and familiarity preference in conjunction with
      attention-shift impairment. The resulting feature maps from learning with novelty
      seeking and with attention-shift impairment are much the same except that
      learning with attention-shift impairment often yields maps with a somewhat better
      discrimination capacity than learning with novelty seeking. In contrast, the
      resulting maps from learning with strong familiarity preference are adapted to
      one of the sources at the expense of the other, and if one of the sources has a
      set of stimuli with smaller variability, the resulting maps are adapted to
      stimuli from that source. When familiarity preference is less pronounced, the
      resulting maps may become normal or fully restricted to one of the sources, and
      in that case, always the source with smaller variability if such a source is
      present. Such learning, in a system with many different maps, will result in very
      uneven capacities. Learning with familiarity preference in conjunction with
      attention-shift impairment surprisingly has higher probability for the
      development of normal maps than learning with familiarity preference alone.

PMID- 15162938
TI  - Spatial frequency and face processing in children with autism and Asperger
      syndrome.
AB  - Two experiments were designed to investigate possible abnormal face processing
      strategies in children with autistic spectrum disorders. A group of 11 children
      with autism was compared to two groups of normally developing children matched on
      verbal mental age and on chronological age. In the first experiment, participants
      had to recognize faces on the basis of identity, emotion, gaze direction, gender,
      and lip reading. All aspects of face processing, except for identity matching,
      were deficient in the autistic population compared with controls. In the second
      study, children had to match faces on either high-(i.e., local facial features)
      or low-spatial frequency information (i.e., global configuration of faces).
      Contrary to the control subjects, children with autism showed better performance
      when using high rather than low spatial frequency, confirming face-processing
      peculiarities in this population.

PMID- 15162939
TI  - Multicultural issues in autism.
AB  - The professional literature provides ample evidence that individuals with autism
      exhibit a myriad of unusual social, communication, and behavioral patterns of
      interactions that present challenges to their families and service providers.
      However, there is a dearth of quality works on multicultural issues regarding
      autistic spectrum disorders. In this article, we explore issues surrounding
      autism and multiculturalism, with the intent not to provide answers but to raise
      questions for further examination. We focus our discussions on two primary
      issues: autism within cultural groups and multicultural family adaptation based
      on the framework of pluralistic societies in which some cultural groups are a
      minority within the dominant culture. We found differences in prevalence rates
      across races for autism and little information regarding how multicultural
      families adapt to raising a child with autism. Further, students with
      multicultural backgrounds and autism are challenged on at least four dimensions:
      communication, social skills, behavioral repertoires, and culture. Future
      research in these areas is clearly warranted.

PMID- 15162940
TI  - Adaptive behavior in autism and Pervasive Developmental Disorder-Not Otherwise
      Specified: microanalysis of scores on the Vineland Adaptive Behavior Scales.
AB  - The purpose of this study is to provide a microanalysis of differences in
      adaptive functioning seen between well-matched groups of school-aged children
      with autism and those diagnosed as having Pervasive Developmental Disorder-Not
      Otherwise Specified, all of whom functioned in the mild to moderate range of
      intellectual impairment. Findings indicate that the major area of difference
      between children with autism and those with Pervasive Developmental Disorder-Not
      Otherwise Specified, was expressive communication; specifically, the use of
      elaborations in syntax and morphology and in pragmatic use of language to convey
      and to seek information in discourse. Linear discriminant function analysis
      revealed that scores on just three of these expressive communication item sets
      correctly identified subjects in the two diagnostic categories with 80% overall
      accuracy. Implications of these findings for both diagnosis and intervention with
      children with Autism Spectrum Disorders will be discussed.

PMID- 15162941
TI  - Brief report: cognitive processing of own emotions in individuals with autistic
      spectrum disorder and in their relatives.
AB  - Difficulties in the cognitive processing of emotions--including difficulties
      identifying and describing feelings--are assumed to be an integral part of
      autism. We studied such difficulties via self-report in 27 high-functioning
      adults with autistic spectrum disorders, their biological relatives (n = 49), and
      normal adult controls (n = 35), using the 20-item Toronto Alexithymia Scale and
      the Beck Depression Inventory. The individuals with autism spectrum disorders
      were significantly more impaired in their emotion processing and were more
      depressed than those in the control and relative groups.

PMID- 15162942
TI  - Ask the editor. Differences between autism and Asperger's disorder.

PMID- 15162943
TI  - [Long-term follow-up of 413 patients with atrioventricular accessory pathway who
      underwent radiofrequency catheter ablation].
AB  - OBJECTIVE: The aim of this study was shown clinical characteristics and follow-up
      of patients with atrioventricular reentrant tachycardia (AVRT) who underwent
      radiofrequency catheter ablation (RCA) therapy. MATERIAL AND METHODS: From April
      1992 to December 1995, 413 patients with AVRT underwent RCA therapy. RESULTS: Two
      hundred thirty four men (57%) and one hundred seventy nine women (43%) aged 31.3
      +/- 16.3 years were studied. 437 single accessory pathways were found; 24 had
      multiple accessory pathways. Ablation therapy was successful in 381 accessory
      pathways. During follow-up of 7 years, AVRT recurred in 51 patients (13%) and in
      80% this occurred within the first 3 months after the procedure. 56 patients
      underwent a second RCA therapy with success in 35 patients (83.5); two reoccurred
      (5.7%); 365 accessory pathways (83.5) remained without evidence of preexcitation
      AVRT. CONCLUSIONS: During follow-up, these patients with successful ablation
      therapy remained without symptoms. In patients who underwent a second RCA
      therapy, atrioventricular reentrant mechanism was always present.

PMID- 15162944
TI  - [Primary testicular lymphomas. Clinicopathologic analysis of 10 cases. Experience
      at the National Institute of Cancerology in Mexico City].
AB  - Non-Hodgkin lymphoma is the most common primary testicular neoplasm of older men
      but is rare in young men. The vast majority of primary testicular lymphomas (PTL)
      are intermediate- to high-grade lymphomas. OBJECTIVE: To describe the clinical,
      morphologic, and immunophenolypic characteristics of PTL seen in a referral
      center. MATERIAL AND METHODS: We reviewed the cases of PTL seen from 1986 to
      1999. We obtained data of laboratory, tests, clinical course, treatment, and
      immunohistochemical studies. RESULTS: 10 patients with diagnosis of PTL were
      identified. Median age was 62.3 years (range 42-81 years), and nine patients
      underwent orchiectomy as initial therapeutic procedure. Other treatment
      modalities after diagnosis included combination chemotherapy (60%) and
      combination radiotherapy (20%). Histologically, testes showed diffuse dense
      infiltration of large lymphoma cells. All cases were classified as diffuse large
      cell lymphoma according to REAL classification. Eight cases were studied with use
      of paraffin-section immunoperoxidase, 7/8 tumors were B-lineage lymphomas, and
      one was a T-lineage lymphoma.

PMID- 15162945
TI  - [Toward development of a Taenia solium paramyosin-based vaccine against porcine
      cysticercosis].
AB  - Taenia solium paramyosin (TPmy) is a prominent 100 kDa antigen in human and
      porcine cysticercosis. TPmy is an alpha-helical coiled coil protein present in
      muscle and tegumentary structures of T. solium cysticerci. TPmy has the property
      of binding C1q resulting in inhibition of the complement cascade. TPmy probably
      binds C1q through its collagen-like domains and could be involved in a parasite
      strategy to modulate host immune response. Humoral immune response against TPmy
      is prefrentially directed against carboxyl terminal end in humans and mice,
      whereas amino terminal end of TPmy preferentially induces a Th1-related cellular
      immune response. Protection studies in murine model of cysticercosis showed that
      the amino terminal end fragment of TPmy induces approximately 60% protection
      against an i.p. challenge with Taenia crassiceps cysts when mice are immunized
      with recombinant fragments of TPmy. Initial protection studies using genetic
      immunization showed that amino terminal end fragment of TPmy cloned into a
      plasmid expression vector with a cytomegalovirus promoter, together with IL-12
      expressing plasmids induced 79% protection, suggesting that this kind of TPmy
      immunization might result in development of a cost-effective vaccine against
      cysticercosis.

PMID- 15162946
TI  - [The quality of life of the asthmatic child caregiver].
AB  - Despite better understanding of the pathophysiology of asthma, the application of
      better drugs (potent anti-inflammatory medications and beta2 adrenergics with
      long-lasting effects), some symptoms persist and the illness itself, at the same
      time with exacerbation, may compromise the integrity of the patient. This calls
      for an evaluation of the impact of the ailment in different aspects of daily life
      of patients and of his/her caregivers. To address these situations, quality-of
      life questionnaires for patients and caregivers were designed. With this study,
      our objective was to make up a quality-of-life questionnaire to be filled out by
      caregivers of asthmatic children treated with one of two therapeutic schemes:
      with inhaled steroids (EI), or the EI plus prolonged action bronchodilator (BAP).
      MATERIALS AND METHODS: Controlled, experimental, and comparative clinical trial
      polling asthmatic child caregivers, applying a questionnaire designed by
      Elizabeth Juniper (PACQLQ). Patients and caregivers were randomized in two
      groups: group A was treated with IE (Beclomethasone) plus BAP (Salmeterol) during
      a 6-week period, followed by a 2-week wash-out period followed by a 6-week period
      with only IE. Group B were treated only with EI followed by a 2-week period of
      wash-out and a six-week period with IE plus BAP. Caregivers filled in the
      questionnaires at the beginning, and at second, fourth, and sixth weeks of
      treatment. RESULTS: We included 30 patients and their caregivers who were
      randomized in two groups. Values in every group showed significant improvement in
      quality of life, as compared to basal values. Values between groups showed
      greater improvement in groups who received EI plus BAP at the beginning.
      CONCLUSIONS: Our study shows that administering treatment for asthma improves
      significantly the caregiver's appreciation of quality of life with respect to the
      PACQLQ questionnaire. The group that received EI therapy plus BAP at the
      beginning showed greater improvement. These results coincide with those published
      to date. We recommend the use of questionnaires at the beginning of the treatment
      as part of the integral evaluation of every patient with asthma.

PMID- 15162948
TI  - [Morbility at the Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco
      Suarez, 1995-2001].
AB  - Hospital statistics are very important as tools that help to define research
      objectives and design health programs. OBJECTIVE: To determine the main causes of
      hospital morbility at the Manuel Velasco Suarez National Institute of Neurology
      and Neurosurgery (MVS-NINN) between 1995 and 2001. MATERIAL AND METHODS: Data
      were taken from the electronic database of morbidity and mortality of MVS-NINN.
      All outpatient records between 1995 and 2001 were considered. We calculated
      trends and specific rates of morbidity per 100 discharged patients. RESULTS: The
      main causes of morbility were brain tumors, schizophrenic illness,
      neurocysticercosis, and stroke. We found a statistically significant declining
      time-trend of schizophrenic illness and in non-traumatic brain hemorrhage in
      males. In the case of females, we observed an increasing time-trend of benign
      meningeal tumors. The age groups more affected in both genders were those < 51
      years of age. CONCLUSIONS: This study is not a population study, but it helps to
      increase knowledge of the main causes of hospitalization at one of the most
      important neurologic institutions in the world, which provides care for thinsured
      population throughout Mexico. These findings facilitate analysis and decision
      making to undertake specifications to improve the quality of neurologic medical
      attention.

PMID- 15162947
TI  - [Prevention of hypoxic-ischemic encephalopathy with high-dose, early
      phenobarbital therapy].
AB  - OBJECTIVE: To assess usefulness of high-dose early phenobarbital therapy for
      prevention of hypoxic-ischemic encephalopathy (HIE) secondary to perinatal
      asphyxia (PNA). MATERIAL AND METHODS: By means of a randomized clinical trial,
      asphyxiated full-term or post-term newborn infants were divided in two groups:
      Group A was the experimental group, while group B was the control group. Infants
      in group A received phenobarbital, 40 mg/kg, during the first 60 min after birth.
      Infants on group B received phenobarbital at conventional doses, only if there
      was clinical evidence of seizures; otherwise, treatment was similar in both
      groups. We estimated frequency of HIE according to Sarnat classification and also
      rate of post-asphyxial complications in other organs. Phenobarbital levels were
      measured in Group A. Statistical tests used were Student t, Mann-Whitney U, X2 or
      Fisher. Informed consent was obtained from parents of each infant. RESULTS: 37
      infants belonged to Group A, while Group B was composed of 36 infants. Both
      groups were similar in sex, gestational age and cord gases. Birth weight was
      higher in Group A (p<0.05). Diagnostic criteria for PNA a cord pH < or = 7.00
      plus one or two criteria of commonly used parameters for asphyxia. There was a
      difference in total dose of phenobarbital and time of initial dose in both
      groups. HIE was present in 13.5% (5/37) of group A, and 22.2% (8/36) of group B.
      Seizures (Stage II of HIE) occurred in 10.8% (4/37) and 11.1% (4/36),
      respectively, without significant statistical difference. There was also no
      difference in rate of post-asphyxial, non-brain complications in both groups.
      There were no side effects or changes in vital signs associated with use of
      phenobarbital. Only one infant had toxic phenobarbital serum levels. DISCUSSION:
      There was no significant difference in the overall frequency of HIE, nor in the
      incidence of seizures or stage II of HIE in both groups. According to these
      results and even though there were no side effects, we think phenobarbital is not
      useful for these purposes. Long-term follow-up of the treated infants is
      justified, since phenobarbital might have a beneficial effect on neuro-behavioral
      development.

PMID- 15162949
TI  - [The Dr. Manuel Gea General Hospital: past, present, and future].

PMID- 15162950
TI  - [Physiopathologic changes in brain death. Their importance for management and
      organ donation decisions].
AB  - Technological advances in the medical area have allowed for development of useful
      techniques to treat patients with diverse diseases. For example, at intensive
      care units this technology allows maintenance blood flow and tissue oxygenation
      even when brain death (BD) is already established and the individual cannot
      function. The function of heart, lungs, and other organs can be maintained with
      different devices, but maintenance of cerebral functions is not not yet possible.
      Therefore, when a subject fulfills legal and medical requirements for BD, we must
      be clear that any patient procedure will not keep him alive, although the subject
      looks alive due to support devices; when BD is present, death must be accepted.
      Obviously, death is a difficult process to accept, including for health
      personnel. We consider that it is very important for medical and nursing
      personnel directly responsible for patient care to receive knowledge on BD and
      recognize the alternatives with regard this situation, to be able to provide
      specific orientation when it is required. This paper is a review of the BD
      concept, main physiopathologic changes, and some possible treatment alternatives
      to maintain the patient as a potential organ donor.

PMID- 15162952
TI  - [Gigantomastia secondary to mineral oil injection. A case report].
AB  - Use injections of illicit material to improve body contour is still a health
      problem in Mexico. Most commonly used are oily materials that in many patients
      may cause aesthetic and incapacitating functional complications. The case of a 32
      year-old homosexual male patient is reported; he was injected with 80 cc of
      mineral oil in each mamma, which caused an important inflammatory reaction,
      growth, and severe ptosis of these. He was in apparent general good shape; thus,
      he was treated with bilateral subcutaneous mastectomy and free full-thickness
      nipple-areola complex graft. We consider that this pathology remains a current
      health problem that should alert health authorities to take preventive measures
      with regard to its administration.

PMID- 15162951
TI  - [Seventy five-year-old man with dysphagia, generalized weakness and dermatosis].

PMID- 15162954
TI  - [Medicine and philosophy, and undissolvable link. Literary focus on contributions
      of Egyptian culture to medicine].
AB  - Medicine and literature are bound humanistically disciplines from the moment that
      Man has the necessity to communicate his restlessness, anguish and fears with
      regard to the presence of illness and death. Medical topics are a frequent
      resource in literary works in which the writer amalgamates the patient, the
      doctor, illness, and death from the human point of view. Specifically in the
      historical quality of the novel, the author is forced nevertheless to be
      documented thoroughly on the topic on which his work rotate, in such a way that
      he avoids incorrect historical data, combined with the necessity to give flight
      to his imagination in the creation of fictitious situations for his narration.
      Here we analyze as example of the details of medicine in the Egyptian culture
      beginning with the novel "Sinuhe the Egyptian", as an answer to scientific
      commentary at an international on congress of neurosurgery.

PMID- 15162956
TI  - [Vaccines against leukemias].

PMID- 15162953
TI  - [Intrathoracic kidney in a newborn with breathing difficulty syndrome secondary
      to congenital diaphragmatic hernia].
AB  - Congenital diaphragmatic hernia (CDH) is found frequently in from 0.17 to 0.57
      among 1000 newborns and is associated with intrathoracic kidney (IK) in 0.25%.
      The objective of the present work was to describe both present pathologies in a
      newborn and to review the literature in this respect. CLINICAL CASE: male
      newborns, who presented tachypnea sudden and persistent for the first 24 h of
      life. For the that was physical exam, we included breathing difficult, (eight
      points of Silverman's) and cyanosis; initial arterial gases: hypoxemia and
      hypocapnia (acute respiratory failure type I); thorax X-ray; increase of
      bronchial plot and of parahiliary density; normal lungs, pleuro-peritoneal
      membrane and solid mass superimposed on heart silhouette were observed and
      confirmed by echocardiogram. Computed axial tomography (CAT) revealed left kidney
      and part of spleen inside thorax, beside inferior lobe of left lung. Immediately,
      the patient was mechanically ventilated and after 2 days, was operated surgically
      for correction of CDH and descent of left kidney. After surgical intervention,
      initial symtomatology disappeared and evolution was satisfactory. The present
      case illustrates how the kidney on occasion can emigrate due to congenital
      default to the thorax of the wall of the diaphragm and be a casual discovery at
      the moment of radiologic exploration.

PMID- 15162955
TI  - [Congenital cystic adenomatoid malformation of the lungs in adults. Computed
      tomographic-surgical-pathologic correlation].

PMID- 15162957
TI  - [A guide for osteoporosis management].
AB  - Osteoporosis has to be considered only as a risk factor for bone fractures and
      its measurement by the bone mass index has some limitations. The aim of treatment
      of osteoporosis is to reduce the frequency of fractures (especially at the
      vertebral and the hip) which are responsible for morbidity and mortality with the
      osteoporosis. It has been demonstrated that antiresorptive drugs
      (bisphosphonates, estrogens, raloxifen) as well as anabolic agents (synthetic
      parathormone) are useful for preventing fractures. Calcium and vitamin D
      supplementation is not sufficient to treat persons with osteoporosis. Choice of
      treatment depends of age, the presence or absence of prevalent fractures, and the
      degree of bone mineral density measured at the spine and hip. The main
      inconvenient for the adherence of treatment is the high cost of the medicaments
      and agents as well as the poor information given to the patients.

PMID- 15162958
TI  - [DNA at the half century].

PMID- 15162959
TI  - [Clarification from the Si-Mujer Foundation].

PMID- 15162960
TI  - [Molecular mechanism of adaptive response to electrophiles].

PMID- 15162961
TI  - [Diversification of Bacteria, Archaea, and Eucarya--a hypothesis based on the
      enantiomeric glycerophospholipids].

PMID- 15162963
TI  - [Glycoproteome analysis].

PMID- 15162962
TI  - [Biological role of AhR signaling pathway].

PMID- 15162964
TI  - [Photoreceptor systems in ascidians: insights into the origin and evolution of
      vertebrate visual systems].

PMID- 15162965
TI  - [Mechanisms of gene expression during adipocyte differentiation].

PMID- 15162966
TI  - [Function and metabolism of D-amino acids in eukaryotes].

PMID- 15162967
TI  - [Identification and function of ubiquitin-like protein SUMO E3 (PIAS family and
      RanBp2, Pc2)].

PMID- 15162968
TI  - [Proteomics using two-dimensional polyacrylamide gel electrophoresis and
      fluorescence dye labeling technology].

PMID- 15162969
TI  - [A review of health economic assessment for liver transplantation--toward social
      acceptance of liver transplantation in Japan].
AB  - This paper reviews the literature on health economics assessment (HEA) for liver
      transplantation (LT) in Europe and USA, and considers prospects in Japan where
      HEA is currently rarely performed. LT is one of the most expensive health
      technologies but the health outcome is generally good. It provides the only well
      established treatment for end-stage liver disease (ESLD) in the Western world,
      while in Japan it has yet to be fully implemented because public acceptance is
      still very low. MEDLINE and Japana Centra Revuo Medicina WEB version Ver. 2
      (JCRM2) were systematically used for the literature search. As a result, 6
      original papers in Europe and USA that employed accurate methods for HEA were
      identified through MEDLINE, indicating that LT is cost-effective on long term
      follow-up. In Japan, however, only one study could be good which tried to
      estimate it's cost-effectiveness, and the methodology was different from that
      used in Europe and USA. Through accurate HEA for LT in Japan, we hope that this
      procedure may become a well-accepted health technology in the future.

PMID- 15162970
TI  - [Evaluation of gender differences of family caregivers with reference to the mode
      of caregiving at home and caregiver distress in Japan].
AB  - PURPOSE: Male caregivers are growing in number, as the frequency of spouse
      caregiving rapidly increases. This study aimed to examine gender differences in
      family caregivers with reference to the mode of caregiving and caregiver distress
      in Japan. It was designed to clarify the characteristics of both female and male
      caregivers. METHODS: The subjects were 2,020 users of public Long-term Care
      Insurance, randomly stratified and sampled in Higashi-osaka city, Osaka
      prefecture. Data were collected through mailed, anonymous self-report
      questionnaires. 1,287 (63.7%) surveys were collected and data from 868 caregivers
      and care recipients were analyzed, after excluding incomplete cases from 947
      participants who were family caregivers. We compared males and females for the
      level of nursing needs, cognitive disorders of their care recipients, the types
      and amounts of care provided, the levels of their burdens and the depression
      associated with providing care, the availability of informal support, the
      frequency of usage of Long-term care insurance services, and the types of stress
      coping strategies. RESULTS: Of the total, 27.1% of the caregivers were male.
      Their age was higher than that of females, but the age of care recipients of
      female caregivers was significantly higher than that of care recipients of males.
      There were no significant gender differences in the level of nursing needs of
      recipients. However, cognitive disorders of care recipients of female caregivers
      were more severe. Female caregivers spent more time providing care, and performed
      a greater number of care activities. In particular, female caregivers assisted
      their care recipients in taking medications, dressing, bathing, eating, meal
      preparation, shopping, laundry, and money management more often to a significant
      degree. Furthermore, the average scores for burden and depression were higher in
      female than in male caregivers. Concerning the usage of Long-term care insurance
      services, males used a Home-helper service more often. Female caregivers used
      types of Informal support seeking and Positive acceptance of caregiving role as
      coping strategies more often than the men. Multiple logistic regression analysis
      indicated that caregiver's subjective burden and types of informal support
      seeking, as well as acceptance of the caregiving role were significantly higher
      in female caregivers. CONCLUSIONS: These results suggest that there are
      significant gender differences regarding the mode of caregiving and experience of
      caregiver distress in Japan. It is important that future research be focused on
      supplying appropriate social support for family caregivers, taking gender
      differences into account.

PMID- 15162971
TI  - [A trial of a smoking rate survey using the coming-of-age ceremony for evaluating
      action plans to prevent tobacco use in the young].
AB  - PURPOSE: To assess a smoking rate survey using the coming-of-age ceremony to
      examine the practicality for estimating the under twenties' smoking rate as a
      baseline and a long term assessment index for action plans to prevent smoking in
      the young. METHODS: We undertook the survey at village A (with a population of
      about 6,500) and town B (with about 12,000 residents) in Niigata Prefecture.
      Village A started a comprehensive anti-smoking policy featuring cooperation
      between schools and the community. Subjects were twenty-year young adults (69 in
      village A and 118 in town B) who attended rural coming-of-age ceremonies in 2002.
      The self-rated questionnaire included smoking habits, age of first smoking
      experience, and age of becoming a regular smoker (only in village A). RESULTS:
      Smoking rates were 68.0% for men and 48.6% for women in village A. Of these,
      approximately 90% smoked daily and more than 70% became regular smokers before
      the age of 20. Smoking rates in town B were similar. The results were about 20%
      higher than found by a smoking rate survey performed at high schools. CONCLUSION:
      Smoking rate surveys at coming-of-age ceremonies offer a practical and easy
      approach to estimate under twenties' smoking rate and assess the effects of
      smoking prevention strategies among the young.

PMID- 15162972
TI  - [Processes and strategies for developing public health nurse directed community
      health projects in municipalities of Japan--focusing on setting agendas and
      making project alternatives].
AB  - PURPOSE: The purpose of this study was to explore processes and strategies for
      developing community health projects directed by public health nurses (PHNs) in
      municipalities of Japan. METHOD: Yin's case study design was adopted into the 5
      step Policy Making Process Model as the theoretical framework. The first two
      steps involving agenda setting and project planning were the focus of this study.
      PHNs who had developed new community health projects in municipalities were
      interviewed as study participants. In order to maintain the quality of projects
      at a certain level, only these approved officially by municipalities with a
      program and budget were selected. RESULTS: Common strategies emerged for
      developing community health projects in the cases presented by the 5 PHNs. Out of
      891 codes, twenty-six sub-categories were identified and integrated into 9
      categories. When categories were analyzed in a time series, the following common
      processes were found: integration of related data, identification of the health
      problems in the community and recognition of project needs (Phase 1); refining
      the concept and characteristics of the project plan (Phase 2); and assuring that
      resources were available for the optimal implementation of the project by
      consolidating ideas (Phase 3). In Phase 1, PHNs integrated the information about
      previous experimental cases or social circumstances to identify community health
      problems needing solution. PHNs' thoughts were given to problems of existing
      projects and daily practices were grouped to make comprehensive plans for
      improvement. In Phase 2, PHNs discussed ideas for the project plans and
      considered resources and strategies that were necessary for putting new projects
      into place. In Phase 3, PHNs were attentive to the factors reviewed in Phase 2,
      kept account of necessary resources, and made certain of timing for immediate
      implementation of plans. The dual roles of PHNs, both as nurses and public
      servants, helped to clarify and solve the community health problems. CONCLUSION:
      Common strategies of developing programs were explored; "Identifying the
      community health problems through analyzing the causes of difficult cases,"
      "Recognizing the necessity of coverall-projects which will improve the existing
      projects," "Understanding the awareness of those involved and discuss ideas for
      the project plan." The findings have based solely on the experiences of PHNs,
      they can provide suggestions that are keys to efficient development of new
      projects.

PMID- 15162973
TI  - [A role and significance of public health center for a tuberculosis epidemic in a
      religious society].

PMID- 15162974
TI  - [Survey of patients with intractable diseases in Kyoto city].
AB  - OBJECTIVE: This study was performed to assess changes over a 5-year period in the
      number of patients with intractable diseases living in Kyoto city who received
      public financial aid for treatment. Variation in the quality of their lives was
      also investigated. METHODS: Questionnaires were mailed to all patients with
      intractable diseases who lived in Kyoto city and who applied for financial aid
      for treatment in 1996 and in 2001. RESULTS: 1. The total number of patients
      increased 1.4-fold over the 5 years (from 4,097 to 5,891). 2. The number of
      patients who required medical treatments increased. Especially a considerable
      number of patients required treatments for secondary conditions ascribable to a
      long-term bed-confined state or prolonged treatment for primary diseases. 3. The
      number of patients who required care to support daily life or hospital visits
      increased 2-fold. 4. It was demonstrated that 52.8% of patients felt their lives
      had improved after the introduction of long-term care insurance system.
      CONCLUSIONS: The number of patients with intractable diseases appears to be
      increasing and their clinical courses are becoming chronic and more severe. This
      situation can be expected to persist in the near future, so that further
      consideration of measures to provide medical care and welfare is necessary.

PMID- 15162975
TI  - [Domestic violence as a women's health issue--activities of health professionals
      in Thailand].
AB  - OBJECTIVES: This paper reports the results of a qualitative study on domestic
      violence (DV) and interventions against DV in Khon Kaen province in northeastern
      Thailand. We analyzed the roles of health professionals for identifying, treating
      and supporting abused women, and examined a network model of DV interventions in
      developing countries. METHODS: We interviewed abused women, health professionals,
      staff of the government and legal authorities, community health workers and other
      relevant people in Khon Kaen city and surrounding areas. We analyzed the health
      consequences of DV, and the roles of health professionals and other actors
      regarding care and assistance for abused women. We also visited and observed
      homes of the victims and health facilities where those women were treated.
      RESULTS AND DISCUSSION: We interviewed 4 abused women in a slum area. One of the
      women was identified by a nurse of a nearby health center and a social worker
      when they visited homes in the area. Another woman was successfully supported by
      nurses of the health center, a community leader and a Buddhist monk. Health
      professionals played important roles in identifying, treating and protecting
      abused women. The Khon Kaen provincial hospital established an One-Stop Crisis
      Center (OSCC) to provide counseling, care and protection for physically or
      sexually abused women, with a team consisting of doctors, nurses and social
      workers who were trained in the care of abused women. The Nampol community
      hospital in a suburban area also established an OSCC to work together with health
      centers and communities for effective intervention. OSCC team members pointed out
      several problems: insufficient mental care, shortage of staff, and the difficulty
      of caring for women coming to the hospital at night or early in the morning. In
      Thailand, a legal framework against DV has yet to be established and government
      agencies are not greatly involved in DV interventions. Health professionals play
      leading roles in identifying, treating and supporting abused women in Thailand.
      It is important to provide relevant training for health professionals and to
      develop cooperation networks with government staff and legal authorities,
      community health workers, and community leaders. Legal frameworks for protecting
      and supporting DV victims are often insufficient in developing countries, while
      health care systems tend to be more reliable. Taking into account the social
      background, health professionals in developing countries can be expected to
      continue to play the most important role in looking after abused women.

PMID- 15162977
TI  - Modeling for a smallpox-vaccination policy against possible bioterrorism in
      Japan: the impact of long-lasting vaccinal immunity.
AB  - BACKGROUND: There has been concern that variola virus might be held clandestinely
      elsewhere. Through constructing mathematical model based on the detailed
      epidemiologic data, we focused on simulating the various possible scenarios
      arising from a bioterrorist attack whereby smallpox virus was introduced into
      Japan, and sought to develop the most effective way of nationwide vaccination
      policy based on the theory of residual immunity. METHOD: The analysis is based on
      a deterministic mathematical model which predicted the epidemiologic outcome
      while simultaneously evaluating the effect of any specified control strategy of
      the smallpox epidemic. To clarify the required amount of vaccines, we performed
      mathematical analysis for hypothetical population to acquire herd immunity based
      on long-lasting vaccinal immunity. RESULTS: It is demonstrated that the crude
      size of the potential epidemic could be greatly affected by possible level of
      residual immunity. The results also suggest the possibility to develop optimal
      distribution of nationwide vaccination according to the immune status. The
      prevalence at 50th day among population without immunity in our simulation would
      be approximately 405 times greater than expected population with residual
      immunity, and required amount of vaccines for equal distribution would be 3.13
      times more than optimal distribution. CONCLUSION: The mathematical model
      formulated could determine the vaccination priority based on the real status of
      immunity which required much less amount of vaccinations than would be calculated
      using an equal distribution program. It is therefore crucial to determine the
      real immunity status of the population via epidemiologic studies.

PMID- 15162976
TI  - Evaluation of a method for issuing warnings pre-epidemics and epidemics in Japan
      by infectious diseases surveillance.
AB  - BACKGROUND: Simple methods have been developed to warn of pre-epidemics and
      epidemics in small areas using data of infectious diseases surveillance. Epidemic
      warnings are made if the index of cases per week per sentinel medical institution
      is greater than a defined value. A pre-epidemic warning means that an epidemic
      warning will be given in the following four weeks. While the methods are used
      routinely for surveillance in Japan, they remain to be validated. METHODS:
      Infectious diseases surveillance data of influenza-like illness and 12 pediatric
      diseases in the fiscal year between 1999 and 2001 were used in the analysis. We
      examined the frequency of warnings, temporal changes in the index before and
      after the onset of a warning, and the sensitivity, specificity, and positive
      predictive value of pre-epidemic warnings. RESULTS: For the majority of the
      diseases investigated, the proportion of weeks in which a warning was issued
      ranged between 0% and 10%. In several diseases including influenza-like illness,
      we observed a rapid increase and gradual decrease in the index before and after a
      warning. The sensitivity, specificity, and positive predictive value of a pre
      epidemic warning were 90.4%, 93.7% and 23.9% for influenza-like illness, and
      ranged between 25.1-54.2%, 86.1-99.2%, and 2.5-20.8% for the pediatric diseases
      (chickenpox, rubella, measles, and mumps), respectively. CONCLUSIONS: The study
      showed that the methods used for determining whether or not to issue an epidemic
      warning were satisfactory in some diseases, including influenza-like illness, and
      may need to be improved in several other diseases.

PMID- 15162978
TI  - Potential errors resulting from sex and age difference in assessing family
      history of coronary heart disease.
AB  - BACKGROUND: Coronary heart disease occurs nearly exponentially with age and
      differently between men and women. Therefore, difference in sex and age of family
      members yields errors in assessing the family history as a risk factor. The
      influence of sex and age on the positivity of family history was assessed
      numerically. METHODS: Through questionnaires filled in by the parents of 2316
      high school students, information was obtained on the past history of coronary
      heart disease among students' parents, grandparents, uncles, and aunts. The sex-
      and age-specific proportion of a positive history was calculated from the past
      history among the 24,071 family members. The influence of sex and age on a
      positive history was estimated as odds ratios by logistic regression analysis of
      the past history. RESULTS: The odds ratios obtained for sex and age difference
      were 1.61 (95% confidence interval: 1.42-1.83) and 1.07 (95% confidence interval:
      1.06-1.07), respectively. This indicated that a positive history was 1.61 times
      higher among male members than among female members of the same age, and that a
      positive history increased by (1.07)y, where y was age difference by year.
      CONCLUSIONS: Potential errors resulting from disregarding the sex and age of
      family members can be substantial, judging from the above numerical figures. Some
      measures to control for the sex and age of family members are required in
      assessing family history of coronary heart disease.

PMID- 15162979
TI  - Role of prehypertension in the development of coronary atherosclerosis in Japan.
AB  - BACKGROUND: Hypertension is an important risk factor of coronary heart disease. A
      new guidelines for hypertension prevention and management in The Seventh Report
      of the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure in the United States recommended lifestyle
      modification or medical treatment for subjects with prehypertension. However,
      whether prehypertension increases the risk of coronary atherosclerosis in the
      Japanese population is still unknown. METHODS: A cross-sectional study in a
      clinical setting was conducted. The subjects were 705 patients (417 males and 288
      females) aged 30 years and older who underwent a first-time coronary angiography
      for suspected or known coronary heart disease at 5 major cardiology departments
      in the Fukuoka metropolitan area between September 1996 and August 1997. RESULTS:
      Compared to subjects with normal blood pressure, those with prehypertension had
      an increased risk of coronary atherosclerosis even after adjusting for other
      factors. CONCLUSION: Prehypertension may be an important clinical entity which
      requires treatment in the Japanese population.

PMID- 15162980
TI  - Non-biochemical risk factors for cardiovascular disease in general clinic-based
      rural population of Bangladesh.
AB  - BACKGROUND: Strategies for preventing premature cardiovascular disease include
      measures to control its risk factors. To plan such activities, prevalence of
      these factors must be known. Data regarding risk factor prevalence is limited in
      Bangladesh and measurement of biochemical factors is not always feasible. The aim
      of our study is to describe the non-biochemical risk factors in a clinic-based
      rural population of Bangladesh that would reflect at least a part of the problem
      in the rural area. METHODS: A cross sectional study was done in a clinic based
      patient population aged 20 years and older (471 males and 800 females) in a rural
      community of Bangladesh. A questionnaire on lifestyle including dietary and
      smoking habit was administered and physical examinations including height,
      weight, waist circumference, and blood pressure were measured in standardized
      way. RESULTS: Mean body mass index was 18.5 kg/m2 (standard deviation [SD]: 2.9
      kg/m2) in males and 18.7 kg/m2 (SD: 3.3 kg/m2) in females. Mean systolic blood
      pressure was 120.0 mmHg (SD: 18.5 mmHg) and mean diastolic blood pressure 77.2
      mmHg (SD: 9.9 mmHg) in all subjects. The prevalence of hypertension (140+/90+
      mmHg and/or on treatment) was 17.8%. Prevalence of tobacco consumption (smoking
      and chewing) was 43.8% in males and 27.1 in females. Prevalence of abdominal
      obesity (waist circumference >94 cm in males, >80 cm in females) was 1.6 % and
      11.4 % for males and females respectively. Proportion of overweight (BMI 25.0+)
      was 3.6%. CONCLUSION: Prevention programs and measures should be emphasized for
      the control of tobacco and hypertension in general, and central obesity in
      females, as far as rural population of Bangladesh is concerned.

PMID- 15162981
TI  - What expectations do young Japanese epidemiologists have for the future of
      epidemiology? A questionnaire survey of members of the young epidemiologists
      society for discussing the future of epidemiology.

PMID- 15162982
TI  - Increasing the dose of furosemide in patients with azotemia and suspected
      obstruction.
AB  - Diuresis renography is widely used to distinguish obstructed from nonobstructed
      kidneys; however, the delivery of furosemide to its site of action in the loop of
      Henle is impaired in patients with azotemia. Consequently, the standard adult
      dose of 40 mg furosemide could be insufficient to generate an adequate diuretic
      response. This problem is illustrated by a patient with azotemia with bilateral
      nephrostomies who underwent Tc-99m MAG3 (mercaptoacetyltriglycine) diuresis
      renography with 40 mg furosemide to determine if his bilateral ureteral
      obstruction had resolved. The study showed findings typical for obstruction
      despite the fact that the patient could not have been obstructed because the
      nephrostomy tubes had not been clamped. When the study was repeated 6 days later
      with 80 mg furosemide and clamped nephrostomy tubes, there was good drainage
      bilaterally excluding obstruction. The nephrostomy tubes were removed and the
      patient's creatinine has subsequently remained stable for 3 years. In summary,
      this report illustrates the rationale for increasing the dose of furosemide in
      patients with azotemia referred for diuresis renography and shows how increasing
      the dose of furosemide could improve the diuretic response and minimize false
      positive or indeterminate results.

PMID- 15162984
TI  - Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron
      emission tomography in a patient taking recombinant erythropoietin.
AB  - F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used
      extensively in oncology to diagnose, stage, and restage patients with various
      malignancies. Many patients treated for malignancies develop neutropenia
      secondary to marrow suppressive chemotherapy and are subsequently treated with
      synthetic hematopoietic growth factors (HGF), both granulocyte-macrophage colony
      stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF).
      Patients taking HGF can present a diagnostic challenge for those interpreting PET
      because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking
      diffuse bone marrow metastases. It has not been reported whether bone marrow
      uptake is affected on PET scans in patients taking erythropoietin, the erythroid
      specific cell-line stimulator. We report a case of extensive diffuse bone marrow
      uptake in a 77-year-old man with a history of colon cancer who began taking
      erythropoietin 3 weeks before his PET scan. This case demonstrates the need to
      consider erythropoietin in the differential diagnosis of possible etiologies
      causing diffuse bone marrow uptake on PET scans.

PMID- 15162983
TI  - Comparison of three different diuretic renal scintigraphy protocols in patients
      with dilated upper urinary tracts.
AB  - PURPOSE: To compare 3 different diuretic renal scintigraphy protocols in patients
      with dilated upper urinary tract. MATERIALS AND METHODS: Three diuresis
      renography protocols were performed in 22 adult patients (28 kidneys) with upper
      urinary tract dilatation. The diuretic was given 20 minutes after (F+20), at the
      same time as (F+0), and 15 minutes before (F-15) radionuclide administration. The
      mean age was 29.8 years (range, 18-43 years). The 3 protocols were identical,
      except for the time of injection of furosemide. The F+0 protocol could not be
      performed in 1 and F-15 in 2 of the patients. Each of the 3 protocols was
      performed for the rest of the patients. The results were classified as
      nonobstructive, equivocal, and obstructive according to the renogram images and
      curves. RESULTS: None of the patients showed equivocal results in both F+0 and F
      15 protocols. In the F+20 studies, 7 of the 28 kidneys were evaluated as
      equivocal. Of these, 5 kidneys showed nonobstructive and 2 kidneys revealed
      obstructive renogram patterns with the other 2 protocols (F+0 and F-15).
      Moreover, one kidney, which was evaluated as nonobstructive in the F+20 protocol,
      showed an obstructive pattern in both F+0 and F-15 protocols. All of the kidneys
      showing obstructive patterns in the F+20 study also revealed obstruction in the
      F+0 and F-15 investigations. We could not find any difference between the
      renogram patterns of F+0 and F-15 investigations. CONCLUSIONS: F+0 and F-15
      protocols allow clarification in cases of equivocal F+20 studies. Because the F+0
      study is more practical and shorter, we suggest the F+0 method when equivocal
      results are obtained by an F+20 study or as a single test when there is only one
      opportunity to confirm or exclude the presence of obstruction.

PMID- 15162985
TI  - A novel case of false-positive I-131 whole-body scan in thyroid carcinoma caused
      by subdural hematoma.
AB  - Iodine-131 whole-body scintigraphy has been used extensively to detect thyroid
      remnants as well as metastatic disease in thyroid carcinoma postthyroidectomy.
      Over the years, numerous causes of false-positive scans have been reported. The
      authors report a novel case of a false-positive result resulting from a subdural
      hematoma mimicking a skull or cerebral metastasis.

PMID- 15162986
TI  - Bone scan demonstrating metastasis to the breast from an ovarian carcinoma and a
      review of the literature.
AB  - Breast metastasis from a primary ovarian neoplasm is very rare. We report a case
      of breast metastasis along with involvement of the liver, spleen, and pelvis from
      ovarian carcinoma in a 54-year-old woman demonstrated by whole-body bone
      scanning. Ovarian metastatic deposits frequently show calcification, and a Tc-99m
      MDP bone scan could be useful in determining the extent of calcified soft tissue
      metastatic spread in these patients. A review of the literature of breast
      metastases form ovarian carcinoma is discussed.

PMID- 15162987
TI  - Tc-99m depreotide detecting malignant pulmonary nodules: histopathologic
      correlation with semiquantitative tumor-to-normal lung ratio.
AB  - Tc-99m depreotide is a synthetic somatostatin analog with a low molecular weight
      of 1358 and binding domains for somatostatin receptors (SSTRs) subtypes 2, 3, and
      5. This agent has been used for imaging pulmonary nodules in an effort to
      differentiate malignancies from infectious processes. To investigate whether
      there is significant ratio variability predicting a specific lung cancer type, we
      undertook this study. We analyzed the semiquantitative tumor-to-normal lung
      ratios among 23 patients with histopathologically proven lung carcinoma. Eleven
      patients with squamous cell carcinoma had 14 nodular lesions (n = 14); the ratios
      ranged from 6.0 to 1.4; the mean was 3.500. Nine patients with adenocarcinoma had
      9 nodular lesions (n = 9); the ratios ranged from 3.2 to 1.0; mean was 1.89.
      Three patients with large cell carcinoma had 3 nodular lesions (n = 3); mean was
      1.2. There were significantly different ratio values between squamous cell
      carcinoma and nonsquamous cell carcinoma. On a statistical analysis by t test,
      this difference proved to have a statistically significant value of P < 0.038.
      For patients with lung cancer, we could predict the tumor most likely to be
      squamous cell carcinoma if the uptake ratio was greater than 3.5. Otherwise, the
      lower ratio appeared to be either the result of large cell carcinoma or
      adenocarcinoma. High tumor uptake of Tc-99m depreotide reflecting abundant SSTRs
      of a tumor and/or peritumoral neovasculature such as squamous cell carcinoma
      could be potentially useful in diagnostic and therapeutic guidance.

PMID- 15162988
TI  - The role of radionuclide bone scintigraphy in fibrous dysplasia of bone.
AB  - PURPOSE: The purpose of this study was to study the characteristics of fibrous
      dysplasia (FD) of bone on bone scans and to evaluate the diagnostic value of
      radionuclide bone scans in FD. METHODS: Radionuclide bone scans were performed in
      42 cases of histopathologically proven FD and the results were compared with
      other imaging modalities. A retrospective study method was used to analyze the
      imaging results. RESULTS: Although FD showed nonspecific increased 99m-Tc MDP
      uptake, its appearance is different than bone metastates and other bone diseases.
      Combining scans with x-rays and other imaging modalities can improve the
      diagnostic accuracy of this disease. CONCLUSIONS: Radionuclide bone scans are of
      certain value in the diagnosis of FD. The diagnostic specificity of FD with
      radionuclide bone scanning can be improved in association with other imaging
      modalities such as x-rays.

PMID- 15162989
TI  - Radionuclide imaging of the thyroid gland: patterns, pearls, and pitfalls.
AB  - Optimal thyroid scintigraphy requires an understanding of 1) the embryology,
      anatomy, and physiology of the thyroid gland; and 2) the properties of the 2
      common imaging agents, technetium-99m pertechnetate (Tc-99m) and radioiodine (1
      123). The normal gland has a characteristic scintigraphic pattern with these
      tracers and its uptake can be quantified with 1-123. Thyroid diseases often
      produce characteristic abnormal patterns. These abnormal patterns could be
      described as diffuse or focal, homogeneous or heterogeneous, increased or
      decreased. "Extrathyroidal" localization can be seen with esophageal activity,
      ectopic tissue, thyroglossal duct cyst, and substernal goiter. Thyroid
      scintigraphy of neonates, as a follow up to abnormal blood screening,
      demonstrates typical etiologic patterns. The first step in evaluating a patient
      with suspected thyroid disease is correlating the normal or abnormal
      scintigraphic pattern with available biochemical data, clinical history, and
      physical examination. By integrating the interpretive and technical "pearls" and
      "pitfalls" outlined in this article, the radiologist can be more confident in
      establishing a proper diagnosis.

PMID- 15162990
TI  - Sternal infection and retrosternal abscess shown on Tc-99m HMPAO-labeled
      leukocyte scintigraphy.

PMID- 15162991
TI  - Inguinal hernia detected on Tc-99m HMPAO-labeled white blood cell study.

PMID- 15162992
TI  - Urine extravasation into the colon detected by Tc-99m DTPA scintigraphy in a
      pyeloduodenal fistula resulting from chronic penetrating duodenal ulcer.

PMID- 15162993
TI  - VIPoma: a rare cause of a pancreatic mass.

PMID- 15162994
TI  - Use of FDG-PET in the differential diagnosis of a single bone lesion in ovarian
      cancer.

PMID- 15162995
TI  - Lepidic spread of primary lung adenocarcinoma on FDG-PET.

PMID- 15162997
TI  - Tc-99m-labeled red blood cell scan showing gastrointestinal bleeding point, and
      also showing an incidental hepatic hemangioma.

PMID- 15162996
TI  - Demonstration of increased FDG activity in Rosai-Dorfman disease on positron
      emission tomography.

PMID- 15162998
TI  - Altered biodistribution of bone seeking agents in the presence of iron-overload.

PMID- 15162999
TI  - Malignant lymphoma with prostate involvement detected by Ga-67 scintigraphy.

PMID- 15163001
TI  - Current readings in nuclear medicine.

PMID- 15163000
TI  - Free technetium: potential pitfall in the diagnosis of renovascular hypertension.

PMID- 15163002
TI  - Evaluation of epidermal growth factor receptor (EGFR) by chromogenic in situ
      hybridization (CISH) and immunohistochemistry (IHC) in archival gliomas using
      bright-field microscopy.
AB  - Overexpression of EGFR secondary to EGFR gene amplification is a common feature
      in primary malignant gliomas. To correctly assess EGFR protein and gene level as
      possible prognostic and predictive markers in gliomas, straightforward assays,
      which can be used routinely in the pathology laboratory to evaluate EGFR status,
      becomes critical. EGFR gene amplification and chromosome 7 aneuploidy was
      detected in 34 formalin-fixed, paraffin-embedded benign and malignant gliomas by
      chromogenic in situ hybridization (CISH) using digoxigenin-labeled EGFR and
      biotin-labeled chromosome 7 centromeric probes. The results were evaluated by
      bright-field microscopy under a 40x objective lens. EGFR protein level was
      detected by immunohistochemistry (IHC) using monoclonal antibody 31G7. Five
      cases, 3 astrocytoma grade III (33%) and 2 glioblastoma multiforme (GBM) (33%),
      had EGFR amplification displayed as diaminobenzidine-stained multiple dots
      suggesting the pattern of double-minute chromosomes. Chromosome 7 polysomy was
      found in 68% gliomas, 100% GBM, 67% astrocytoma grade III, 42% astrocytoma grade
      II, 50% astrocytoma grade I, 100% ependymoma, and the 1 case of mixed glioma III.
      High expression of EGFR protein was present in 62% gliomas and displayed membrane
      and cytoplasmic staining. All tumors with EGFR gene amplification showed EGFR
      high expression. High expression of EGFR without gene amplification was observed
      in all grades of gliomas. Simultaneous detection of EGFR gene copies or
      chromosome 7 centromere signals along with tissue morphology allows us to compare
      CISH results easily with IHC results. Our results show that CISH is an objective,
      practical, and accurate assay to screen for EGFR gene status in gliomas.

PMID- 15163003
TI  - Detection of hepatitis C virus RNA in formalin-fixed paraffin-embedded sections
      with digoxigenin-labeled cRNA probes.
AB  - Although recent studies have analyzed Hepatitis C (HCV) infections in liver
      tissue by in situ hybridization (ISH), many of these studies have been of limited
      diagnostic utility because of the low copy numbers of HCV in formalin-fixed
      paraffin-embedded (FFPE) tissue and failure to correlate the ISH analysis with
      other methods of detecting HCV. Thirty six cases of liver biopsies from patients
      with known HCV antibody status including 20 cases of serum HCV positive and 16
      cases of serum HCV negative were analyzed. All cases showed histologic features
      suggestion of HCV infection. Analyses of all 36 cases were done by RT-PCR
      combined with Southern hybridization (RT-PCR-SH) and in situ hybridization (ISH).
      A prolactin riboprobe was used as a negative control. Immunohistochemistry (IHC)
      with an antibody against HCV (Rb 246) was also used to analyze HCV viral protein
      in the tissues. Of the 20 serum antibody-positive cases, RT-PCR-SH detected 18
      positive cases, while ISH and IHC detected 19 and 16 positive cases,
      respectively. Of the 16 serum antibody-negative cases, RT-PCR-SH detected 8
      positive cases while ISH and IHC detected 8 and 11 positive cases, respectively.
      A positive ISH signal for HCV was also detected in some lymphocytes and bile
      ducts in the liver. These results show that ISH with a highly specific riboprobe
      is comparable to RT-PCR-SH for detection of HCV infection in liver tissue.

PMID- 15163004
TI  - Detection of polyoma virus in brain tissue of patients with progressive
      multifocal leukoencephalopathy by real-time PCR and pyrosequencing.
AB  - We evaluated 2 methods, a LightCycler PCR assay and pyrosequencing for the
      detection of the JC polyoma virus (JCV) in fixed brain tissue of 10 patients with
      and 3 control patients without progressive multifocal leukoencephalopathy (PML).
      Nucleic acid extraction was performed after deparaffinization and proteinase K
      digestion. The LightCycler assay differentiates the BK virus (BKV), JCV, and SV40
      using melt curve analysis. Conventional PCR was used with the same primers to
      generate products for pyrosequencing. Two sequencing primers were used that
      differentiate the polyoma viruses. Seven of 11 biopsies (1 patient had 2
      biopsies) with PML were positive for JCV by real-time PCR and/or
      PCR/pyrosequencing. Three of 4 remaining biopsies were positive by real-time PCR
      but had melting points between JCV and SV40. The 4 specimens that were negative
      or atypical by LightCycler PCR were positive by traditional PCR, but 1 had an
      amplicon of lower molecular weight by gel electrophoresis. These were shown to
      represent JCV by at least 1 of the 2 pyrosequencing primers. The biopsies from
      patients without PML were PCR negative. Both the LightCycler and pyrosequencing
      assays are useful for confirming JCV in brain biopsies from patients with PML,
      but variant JCVs may require supplementary methods to confirm JCV infection.

PMID- 15163005
TI  - High-resolution array-based comparative genomic hybridization for distinguishing
      paraffin-embedded Spitz nevi and melanomas.
AB  - Distinguishing between Spitz nevus and melanoma presents a challenging task for
      clinicians and pathologists. Most of these lesions are submitted entirely in
      formalin for histologic analysis by conventional hematoxylin and eosin-stained
      sections, and fresh-frozen material for ancillary studies is rarely collected.
      Molecular techniques, such as comparative genomic hybridization (CGH), can detect
      chromosomal alterations in tumor DNA that differ between these 2 lesions. This
      study investigated the ability of high-resolution array-based CGH to serve as a
      diagnostic test in distinguishing Spitz nevus and melanoma using DNA isolated
      from formalin-fixed and paraffin-embedded samples. Two of 3 Spitz nevi exhibited
      no significant chromosomal alterations, while the third showed gain of the short
      arm of chromosome 11p. The latter finding has previously been described as
      characteristic of a subset of Spitz nevi. The 2 melanomas showed multiple copy
      number alterations characteristic of melanoma such as 1q amplification and
      chromosome 9 deletion. This study has shown the utility of array-based CGH as a
      potential molecular test in distinguishing Spitz nevus from melanoma. The assay
      is capable of using archival paraffin-embedded, formalin-fixed material; is
      technically easier to perform as compared with conventional CGH; is more
      sensitive than conventional CGH in being able to detect focal alterations; and
      can detect copy number alterations even with relatively small amounts of lesional
      tissue as is typical of many skin tumors.

PMID- 15163006
TI  - Relationship between mitochondrial DNA instability, mitochondrial DNA large
      deletions, and nuclear microsatellite instability in head and neck squamous cell
      carcinomas.
AB  - Mitochondrial DNA (mtDNA) mutations in coding and noncoding regions have been
      reported in a variety of human cancers. Despite a greater number of studies, the
      relationship between such alterations and nuclear microsatellite instability
      (nMSI) of the tumor cells remains controversial. To contribute new data to this
      discussion, we investigated head and neck squamous cell carcinomas (HNSCC) for
      mutations and mitochondrial microsatellite instability (mtMSI) in 2 parts of the
      mitochondrial D-loop as well as mutations in 2 mitochondrial genes and for the
      delta4977 mtDNA deletion. These results were compared with data of an analysis
      for microsatellite instability at IGFIIR, hMSH3, hMSH6, and 5 dinucleotide
      repeats. We found mtMSI, low nMSI, and high nMSI in 42%, 36%, and 13% of HNSCC
      primary tumors, respectively. A de novo delta4977 mtDNA deletion could be
      demonstrated in 25% of HNSCCs. A correlation between mtMSI and nMSI or between a
      de novo occurrence of the delta4977 mtDNA deletion and nMSI could not be detected
      in our HNSCC samples (P values 0.527 and 0.078, respectively). Nevertheless, the
      high rate of mtMSI suggests an involvement of mtDNA alterations in the
      tumorigenesis of this head and neck cancer and supports the proposal that this
      aberration may be a new tumor marker.

PMID- 15163007
TI  - Definition of a region of loss of heterozygosity at chromosome 11q23.3-25 in head
      and neck squamous cell carcinoma using laser capture microdissection technique.
AB  - To date, loss of heterozygosity (LOH) studies on HNSCC have had limited success
      in identifying a confined region of loss on chromosome 11q partially due to the
      heterogeneous nature of tumor tissue examined. Additionally, little is known
      about the role of the 11q allelic deletion in HNSCC tumorigenesis and current
      reports are conflicting. The aim of this study was to better define LOH at distal
      11q by using combination of a pure cell population procured by laser capture
      microdissection (LCM) and subsequent sensitive PCR amplification of polymorphic
      microsatellites. This study analyzed HNSCC for LOH using a panel of 5
      microsatellite markers spanning 11q23-25. Thirty-four paired DNA samples from
      tumor and autologous normal tissue were harvested by LCM technique to ensure a
      pure cell population for PCR amplification. Approximately 2000 to 3000 cells were
      procured from each sample. Twenty-one of 34 cases (62%, P < 0.001) showed LOH on
      at least one of the loci examined. The highest frequency of LOH was found at the
      11q23.3-25 segment, with 44% at marker D11S968 and 35% at marker D11S1316. A
      distinct novel region of frequent LOH at 11q23.3-25, defined by D11S1316 and
      D11S968, was identified. No allelic loss was found in any normal squamous tissue
      samples. To study LOH in HNSCC, combination of pure cell population procurement
      by LCM and sensitive PCR provides a more accurate approach than the conventional
      method using a bulk of heterogeneous tissue. A novel region of LOH at 11q23.3-25
      was defined. LOH in this region may harbor putative tumor suppressor gene(s)
      critical for HNSCC. Furthermore, these allelic losses were not found in any non
      neoplastic squamous tissue samples, clarifying prior discrepant data.

PMID- 15163008
TI  - Tumor suppressor gene allelic loss profiles of the variants of papillary thyroid
      carcinoma.
AB  - Papillary thyroid carcinoma (PTCa) is a relatively common, indolent tumor that
      usually has an excellent prognosis. While the diagnosis of conventional PTCa is
      relatively straightforward, encapsulated tumors with follicular growth pattern
      and unusual or incomplete cytologic features of papillary carcinoma can be
      diagnostically challenging. Encapsulated, noninvasive tumors are particularly
      controversial as the differential diagnosis includes a nonneoplastic nodule, a
      benign follicular adenoma, and papillary carcinoma. In this study, we performed
      molecular genotyping to identify loss of heterozygosity of tumor suppressor genes
      in conventional PTCa and in several different morphologic variants, including
      follicular variant, tall cell variant, and oncocytic variant. Our data
      demonstrate that conventional PTCas have the lowest frequency of allelic loss
      (7%), as compared with follicular, oncocytic, and tall cell variants (19%, 34%,
      and 20%, respectively). Frequency of allelic loss increased with increasing size
      of the tumors, but did not correlate with age, gender, extrathyroidal extension,
      or lymph node metastases. Though it is unlikely that these results will enable
      the distinction between different variants of papillary carcinoma, the finding of
      significant rates ofallelic loss in the variants of PTCa provides additional
      evidence of malignancy and may be useful in distinguishing encapsulated tumors
      from nonneoplastic or benign nodules.

PMID- 15163009
TI  - A novel case of synovial sarcoma of the kidney: impact of SS18/SSX analysis of
      renal hemangiopericytoma-like tumors.
AB  - We report a new case of synovial sarcoma of the kidney. The patient underwent
      nephrectomy because of a large tumor in the right kidney. The histologic
      diagnosis was hemangiopericytoma. Less than 1 year after primary surgery the
      patient was reoperated due to massive local recurrence. Histology now revealed a
      poorly differentiated tumor tissue with hemangiopericytoma-like features.
      Immunostainings showed immunoreactivity to cytokeratin, epithelial membrane
      antigen, and vimentin. The tumor was negative to CD34 and factor VIII. The tumor
      cell proliferation, assessed by Ki-67, was high. RT-PCR analysis and sequence
      analysis demonstrated the presence of SS18/SSX2 fusion gene. Review of the
      histologic specimens from the original tumors confirmed hemangiopericytoma-like
      morphology. The new diagnosis was poorly differentiated synovial sarcoma. At the
      time of reoperation, lung metastases were detected radiologically, reflecting a
      very aggressive phenotype. To our knowledge, this is the third case of poorly
      differentiated synovial sarcoma of the kidney. Common for all these three cases
      is the hemangiopericytoma-like histology and a very aggressive clinical behavior.
      These circumstances accentuate the impact of SS18/SSX analysis in diagnosis of
      renal hemangiopericytoma-like tumors.

PMID- 15163010
TI  - A poorly differentiated synovial sarcoma (SYT/SSX1) expresses neuroectodermal
      markers: a xenografts and in vitro culture study.
AB  - Synovial sarcoma (SS) is a neoplasm that poses diagnostic problems, due to its
      histologic heterogeneity. The poorly differentiated variant, in particular, may
      be histologically indistinguishable from other small round cell tumors. Detection
      of the synovial sarcoma-associated t(X;18) or SYT-SSX fusion transcripts may be
      necessary to confirm the diagnosis of SS in difficult cases. Most of SS carry a
      t(X;18) in about one third of cases as the sole cytogenetic abnormality. We
      evaluated a case of poorly differentiated synovial sarcoma and their derived
      tumors in nude mice xenografts and cell cultures. We used a panel of antibodies
      (including those to intermediate filament, nerve-sheath associated markers, and
      neuronal and neuroectodermal related antigens) to better establish the
      immunophenotype, supported by the ultrastructural evaluation. The tumor exhibited
      the distinctive cytogenetic abnormality t(X;18), together with a
      der(1)t(1;22)(p36;q12). Present results show that this poorly differentiated
      synovial sarcoma not only expresses conventional biologic and genetical markers
      for SS but also neuroectodermal features when transplanted into nude mice and
      cultured in vitro.

PMID- 15163011
TI  - Quantitation in immunohistology: fact or fiction? A discussion of variables that
      influence results.

PMID- 15163012
TI  - Immunohistochemical evaluation of hormone receptors in breast cancer: which
      scoring system is suitable for highly sensitive procedures?
AB  - To evaluate hormone receptors immunohistochemically, standardized staining
      procedures and scoring systems are required. The authors previously reported that
      highly sensitive procedures affected basic factors for technical validation. The
      aim of the present study was to show the characteristics of scoring systems for
      highly sensitive procedures. To examine how highly sensitive procedures enhance
      the staining intensity and increase the positive cell population, two different
      staining methods were compared. To evaluate scoring systems, three systems--cell
      counting score, modified immunoreactive score, and H score--were compared using
      the same samples stained by an autostaining system. It was found that the highly
      sensitive procedure increased the positive cell population, especially in breast
      cancers with a low enzyme immunoassay (EIA) level of less than 100 fmol/mg, and
      strengthened the staining intensity. This enhancement led to a correlation in a
      logarithmic curve rather than a linear correlation by all three scoring systems.
      The results showed that scoring systems including a factor of staining intensity
      did not have an absolute advantage because boosted staining intensity by highly
      sensitive procedure did not reflect EIA value or protein contents accurately. To
      the authors' knowledge, there is no report discussing the nonlinear correlation
      between biochemical and immunohistochemical assay by highly sensitive procedures;
      however, it is important to select a scoring system and threshold based on
      nonlinear correlation.

PMID- 15163013
TI  - HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in
      situ hybridization and immunohistochemistry with special focus on intratumor
      heterogeneity and comparison of invasive and in situ components.
AB  - We have studied the intratumor HER-2/neu heterogeneity in 78 consecutive and
      population-based primary invasive breast carcinomas. Within the invasive
      component, heterogeneity was detected in only 1 of 78 tumors. In 48 tumors (62%),
      we found both in situ and invasive components in analyzed tissue sections. Twelve
      of these 48 tumors had a difference of at least 2 arbitrary units in the in situ
      compared with the invasive part of the tumor with regard to the HER-2/neu status
      analyzed by HercepTest (immunohistochemistry). Eight of these 12 tumors were
      reanalyzed with fluorescent in situ hybridization and immunohistochemistry with
      and without a new Automated Cellular Imaging System. In this limited material,
      immunohistochemistry in combination with the Automated Cellular Imaging System
      seemed to have a better correlation with fluorescent in situ hybridization than
      immunostaining analyzed manually. In conclusion, HER-2/neu expression is not
      seldom heterogeneous in invasive compared with in situ components within a tumor.
      This finding should be considered in the choice of evaluation method. To avoid
      heterogeneity as a confounding factor in HER-2/neu analyses, detection methods
      such as immunohistochemistry and fluorescent in situ hybridization, which can
      provide evaluation in a preserved tissue architecture, should be used. Perhaps
      the intratumor HER-2/neu heterogeneity can explain some of the unexpected
      failures of trastuzumab therapy.

PMID- 15163014
TI  - Expression of the diffuse B-cell lymphoma family molecule SWAP-70 in human B-cell
      neoplasms: immunohistochemical study of 86 cases.
AB  - SWAP-70 is a recently discovered member of the Dbl (diffuse B-cell lymphoma)
      family of signal transduction molecules that is abundantly expressed in B cells.
      SWAP-70 mediates lipid second-messenger signals to the cytoskeletal-organizing
      GTPase Rac, functioning as a guanine-nucleotide exchange factor. SWAP-70 is
      strongly expressed in germinal center B cells, with low-level expression in
      resting B-cells. Expression of SWAP-70 in neoplastic B cells has not been
      described. We report the immunohistochemical expression of SWAP-70 in 86 B-cell
      neoplasms. SWAP-70 was strongly expressed in 59 of the 86 cases: 2 of 10 (20%)
      precursor B-cell lymphoblastic leukemias, 2 of 2 (100%) precursor B-cell
      lymphoblastic lymphomas, 2 of 4 (50%) mantle cell lymphomas, 7 of 9 (78%) Burkitt
      lymphomas, 9 of 9 (100%) diffuse large B-cell lymphomas, 8 of 8 (100%) follicular
      lymphomas, 6 of 6 (100%) nodular lymphocyte predominant Hodgkin lymphomas, 0 of 8
      (0%) classic Hodgkin lymphomas, 12 of 13 (92%) chronic lymphocytic leukemias, 3
      of 3 (100%) nodal marginal zone lymphomas, 5 of 5 (100%) extranodal marginal zone
      lymphomas, 1 of 2 (50%) splenic marginal zone lymphomas, 2 of 3 (66%) hairy cell
      leukemias, and 0 of 4 (0%) plasma cell neoplasms. All 4 T-cell lymphomas were
      nonreactive for SWAP-70: 0 of 3 peripheral T-cell lymphomas and 0 of 1 anaplastic
      large cell lymphoma. These results suggest that a spectrum of neoplastic B cells
      maintains activation of this signal transduction pathway. This is the first
      report of the expression of a Dbl family molecule in human lymphoma and leukemia
      tissues.

PMID- 15163015
TI  - Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma.
AB  - The anatomic distribution and rate of progression vary significantly between
      acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) and classic
      KS. The reasons are unclear, but cyclin D1 overexpression is associated with
      tumor progression in other malignancies. Cyclin D has an important regulatory
      role in the progression of cell cycle at the G1-S phase due to its effect in
      phosphorylating the retinoblastoma gene product. Forty-one paraffin-embedded
      surgical specimens (31 AIDS-related, 10 classic) were examined using streptavidin
      biotin-peroxidase immunohistochemistry with monoclonal antibody to cyclin D1. A
      scoring system based on the intensity and extent of staining was used. The
      correlations among cyclin D1 expression and clinicopathologic parameters were
      statistically analyzed. Cyclin D1 overexpression was found in 29% (12/41) of all
      KS cases. There was a strong correlation between cyclin D1 overexpression and
      pathologic stage (0% in patch stage, 13% in plaque stage, 50% in nodular stage; P
      = 0.0017). Classic KS lesions had a higher incidence of cyclin D1 overexpression
      than AIDS-related lesions (70% vs 16%, P = 0.001). Cyclin D1 overexpression was
      detected in 78% of the classic nodular lesions and 31% of the AIDS-related
      nodular lesions (P = 0.03). On multivariate analysis, negative human
      immunodeficiency virus status (P = 0.001) and nodular lesions (P = 0.007) were
      strong predictors of cyclin D1 overexpression. Age, gender, recurrence of the
      tumor, multiplicity, and site of the lesions hold no statistically significant
      association with cyclin D1 expression on multivariate analysis. In summary,
      cyclin D1 overexpression was more prevalent in classic lesions and more advanced
      nodular stage. These findings raise the possibility of a different pathogenetic
      mechanism in the progression of AIDS-related KS and classic KS.

PMID- 15163016
TI  - Microvascular density does not correlate with histopathology and outcome in
      neuroendocrine tumors of the pancreas.
AB  - Microvascular density (MVD), a marker for tumor angiogenesis, has been
      demonstrated to have prognostic significance in various malignancies. Previous
      studies have demonstrated that MVD is an independent prognostic factor in
      pancreatic adenocarcinoma and that longer survival is associated with
      hypovascular tumors. The prognostic importance of MVD in pancreatic
      neuroendocrine tumor (NET) has not been documented. We evaluated MVD in
      pancreatic NET and correlated it with clinicopathologic features and patient
      outcome to determine whether MVD is a useful prognostic indicator for these
      patients. Twenty-five pancreatic NETs from our archival files resected between
      1981 and 2000 were identified. The mean MVD was determined for each tumor from
      the 3 most vascularized 200 x fields. Clinical follow-up ranged from 1 to 19
      years, with a mean of 4.9 years. At last follow-up, 6 patients were dead of
      disease, 10 patients were alive without disease, 4 patients were alive with
      disease, and 5 patients were alive with disease status unknown. Mean MVD ranged
      from 43 to 527 microvessels per 200 x field. MVD did not correlate with tumor
      size, the examined histologic parameters, or patient outcome. MVD in pancreatic
      NET does not correlate with the clinicohistologic features evaluated in this
      study or with the patient outcome and is not a useful prognostic indicator in
      these patients. These results suggest that factors other than the simple number
      of microvessels are important in determining pancreatic NET behavior. However,
      most tumors were highly vascular, and additional studies may be helpful to
      clarify further the role of vascularity and assess the utility of antiangiogenic
      agents in the treatment of pancreatic NET.

PMID- 15163017
TI  - Enhanced detection of atypical hyperplasia in endometrial polyps by PTEN
      expression.
AB  - Endometrial hyperplasia is difficult to recognize within endometrial polyps
      because of the background of randomly distributed irregular glands. The loss of
      expression of the PTEN oncogene is characteristic of endometrial cancers and
      clinically significant hyperplasia. Using immunohistochemical staining for the
      PTEN protein, we studied 12 endometrial polyps that were noted to contain foci of
      complex hyperplasia or glandular crowding. Loss of PTEN staining was found in 3
      cases, suggesting a precancerous lesion. Moreover, 2 of these cases were
      originally classified as complex hyperplasia without atypia and 1 as merely
      glandular crowding. Thus, in selected cases, the loss of PTEN expression in an
      area of glandular crowding can highlight biologically significant lesions and
      afford a more definitive diagnosis.

PMID- 15163018
TI  - Immunohistochemical localization of survivin in serous tumors of the ovary.
AB  - The aim of this study was to determine the immunohistochemical distribution of
      survivin in benign, borderline, and malignant serous tumors of the ovary.
      Survivin was localized by an indirect immunoperoxidase method in 42 cases of
      serous tumors of the ovary (15 cystadenomas, 15 borderline tumors, and 12
      cystadenocarcinomas). Nuclear staining and cytoplasmic staining were separately
      scored. Cytoplasmic staining was detected in 27% of adenomas/borderline tumors
      and in 58% of carcinomas. Nuclear staining was detected in 87% of
      adenomas/borderline tumors but in only 42% of carcinomas. Although the
      differences in the intensity of cytoplasmic staining between adenomas and
      borderline tumors versus carcinomas were not significant, the differences in the
      intensity of nuclear staining between low-grade versus malignant tumors were
      significant. These findings suggest that survivin is widely expressed in benign,
      borderline, and malignant serous tumors but that nuclear localization of survivin
      is more common in benign or borderline tumors than in malignant serous tumors of
      the ovary. The molecular mechanisms that determine the subcellular distribution
      of this protein may reflect the role of survivin in the regulation of apoptosis
      during the processes of malignant transformation.

PMID- 15163019
TI  - Prognostic significance of anti-apoptosis proteins survivin and bcl-2 in non
      small cell lung carcinomas: a clinicopathologic study of 102 cases.
AB  - Inhibitors of apoptosis, including bcl-2 and survivin (a novel gene encoding a
      unique apoptosis inhibitor), regulate cell proliferation by promoting cell
      survival. Although survivin has been detected in several human cancers, its
      prognostic significance and relationship to bcl-2 are not well characterized in
      lung cancer. Tissue sections from 102 non-small cell lung carcinomas (NSCLC) were
      immunostained using antibodies against survivin and bcl-2. Staining results were
      correlated with prognostic variables. Immunoreactivity for survivin and bcl-2 was
      observed in 53% and 21% of NSCLCs, respectively. Fifty-two percent of the 50
      squamous cell carcinomas and 54% of the 52 adenocarcinomas expressed survivin.
      Survivin positivity correlated with tumor stage in squamous cell carcinoma. On
      univariate analysis, survivin expression correlated with decreased patient
      survival in NSCLC and in the subset of squamous cell carcinomas, but not in
      adenocarcinomas. On multivariate analysis, survivin was an independent predictor,
      along with distant metastasis and large tumor size. Eighteen percent of squamous
      cell carcinomas and 24% of adenocarcinomas expressed bcl-2. On univariate
      analysis, bcl-2 expression correlated with increased patient survival in NSCLC
      and in the subset of squamous cell carcinomas. An inverse correlation between the
      expression of survivin and bcl-2 was noted. Survivin immunoreactivity is an
      independent predictor of shortened survival in NSCLC, while bcl-2 protein
      expression correlated with prolonged patient survival. These findings indicate an
      inverse relationship between survivin and bcl-2 expression and suggest that these
      two inhibitors of apoptosis function through different pathways in the regulation
      of tumorigenesis in NSCLC.

PMID- 15163020
TI  - Immunohistochemical and ultrastructural comparative study of external lamina
      structure in 31 cases of cellular, classical, and melanotic schwannomas.
AB  - Unlike most soft tissue tumors, schwannoma is characterized by the presence of
      distinct linear, frequently duplicated external lamina (EL). Although electron
      microscopy remains the gold standard for demonstrating this unique feature and
      distinguishing its morphologic variants from mimickers, the use of two anti-EL
      antibodies, laminin and type IV collagen, appears to supersede electron
      microscopy in terms of current practice. To determine whether immunohistochemical
      expression correlates with ultrastructural findings, 10 cellular schwannomas, 18
      classic schwannomas, and 3 melanotic schwannomas were evaluated ultrastructurally
      and immunohistochemically using antibodies to type IV collagen and laminin.
      Immunohistochemically, a moderate to strong intensity in more than 50% of tumor
      cells was detected using either antibody in most cases of cellular schwannomas
      (70%), the Antoni A areas of classic schwannomas (78%), and melanotic schwannomas
      (67%). Ultrastructurally, the presence of diffusely continuous, duplicated EL was
      observed in 30% of cellular schwannomas and 56% of classic schwannomas, while 50%
      of cellular schwannomas and 22% of classic schwannomas showed either continuous
      simple EL or discontinuous but duplicated EL alone. In addition, two cellular
      schwannomas (20%) and four classic schwannomas (22.2%) had only a simple layer of
      EL in focal areas. In contrast to the distinct immunostaining surrounding
      individual cells seen in the former two subtypes, all three melanotic schwannomas
      displayed a biphasic-staining pattern of the EL (ie, individual cell and nested),
      which was confirmed at the ultrastructural level. The authors found a significant
      difference in intensity between the Antoni A and B areas of classic schwannomas
      using both laminin and type IV collagen. In addition, the intensities of laminin
      and type IV collagen in the Antoni A areas of classic schwannomas were
      significantly stronger compared with those of cellular schwannomas. Nevertheless,
      there was no significant difference either between two antibodies or between
      cellular and classic variants with regard to the extent of immunoreaction. Only
      in classic schwannomas did the extent of immunoreaction against both laminin and
      type IV collagen correlate significantly with the ultrastructural EL distribution
      pattern (diffusely continuous vs. discontinuous). However, this association was
      not detected in cases of cellular schwannomas. On the other hand, the intensities
      of laminin and type IV collagen did not correlate with the ultrastructural
      thickness of EL, irrespective of the morphologic subtypes. In conclusion, both
      type collagen IV and laminin are still reliable markers of EL in various types of
      schwannomas. Schwannomas exhibiting a monolayered EL are as strong in
      immunoreaction as those displaying reduplicated/thickened EL, indicating that a
      single layer of EL is thick enough to be identified by both antibodies with
      sufficient sensitivity. The peculiar biphasic EL pattern seen in melanotic
      schwannoma remains under-recognized, which may lead to misdiagnosis as malignant
      melanomas, especially in limited biopsy specimens.

PMID- 15163021
TI  - Inflammatory fibroid polyps of the gastrointestinal tract: clinical, pathologic,
      and molecular characteristics.
AB  - Inflammatory fibroid polyp (IFP) of the gastrointestinal tract is an uncommon
      proliferative lesion. When sampled by biopsy, IFP can be mistaken for various
      lesions, from granulation tissue to high-grade sarcoma. We present an unusual
      case of IFP and review a large series of IFPs to characterize clinical,
      histologic, and molecular features of diagnostic value. A total of 42 IFPs were
      gathered from the pathology archives of the University of Pittsburgh Medical
      Center over the past 22 years. Clinical, histopathologic, and immunohistochemical
      features were collected. A random subset of IFPs (n = 12) underwent
      microdissection genotyping for a broad panel of tumor suppressor gene-associated
      mutations (loss of heterozygosity). IFPs occurred in both sexes (male, 17;
      female, 25) over a broad age range (29-85 years). IFPs varied in size from 0.2 to
      8 cm. The stomach (n = 19) was the most common location, followed by large bowel
      (n = 13) and small bowel (n = 10). Most IFPs displayed typical morphologic
      features (eosinophils admixed with loose, mature fibrous tissue), and in 2
      instances, sampled by biopsy, IFP was confused for sarcoma. All IFPs lacked c-kit
      staining. No mutations were identified in any IFPs examined. IFP is a clinically
      underrecognized entity with unique morphologic and immunohistochemical features.
      On biopsy alone, the differential diagnosis may include sarcoma and other
      malignancies. The absence of mutational change may help to exclude malignant
      lesions.

PMID- 15163022
TI  - Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using
      tissue microarrays.
AB  - The c-erbB-2 and cyclooxygenase (COX) pathways are involved in the pathogenesis
      of colorectal carcinoma, but the relationship is not fully understood. This study
      evaluated the significance of c-erbB-2, COX-2, and Ki-67 protein expression in
      185 patients with colorectal carcinoma using tissue microarrays. Only one case
      expressed cerbB-2 protein. COX-2 expression was noted in 166 of 176 cases
      (94.3%), and the Ki-67 expression rate averaged 5.9%. There was no relationship
      among c-erbB-2, COX-2, and Ki-67 protein expression, and COX-2 protein expression
      was not related to tumor stage, differentiation, size, depth of invasion,
      lymphatic or vascular invasion, or patient survival. While the contribution of c
      erbB-2 to colorectal carcinogenesis may be of little quantity, COX-2 may be
      deeply involved in colorectal carcinogenesis.

PMID- 15163023
TI  - Immunohistochemical expression of cyclooxygenase-2 in normal kidneys.
AB  - Cyclooxygenase (COX)-2, the recently described inducible form ofcyclooxygenase,
      has been shown to be responsible for the inflammatory and tumorigenic effects of
      prostaglandins; hence the development and expanding clinical use of COX-2
      selective inhibitors termed super aspirins. These pharmacologic agents block COX
      2 without abrogating the desired physiologic roles of the constitutively
      expressed isoform COX-1. Therefore, they are now used in place of nonselective
      COX inhibitors in patients who require prolonged use of nonsteroidal anti
      inflammatory agents. However, there are sporadic reports of COX-2-related
      nephrotoxicity, and the mechanism of this adverse reaction is not known. Also,
      the pattern of in situ expression of COX-2 in the human kidney is not known. We
      therefore studied the immunohistochemical expression of COX-2 in normal kidneys
      obtained from 53 consecutive total nephrectomy specimens. COX-2
      immunohistochemistry was performed using affinity purified polyclonal murine
      antibody and avidin-biotin detection method with citrate antigen retrieval. Also,
      to localize COX-2 expression to specific cell types, double immunolabeling was
      performed using avidin-biotin (for COX-2 detection) and alkaline phosphatase (for
      detection of alpha-smooth muscle actin or factor VIII related antigen). In the
      cortex, COX-2 was found to be constitutively expressed in the endothelial cells
      of arteries, arterioles, and glomeruli in all 53 kidneys. COX-2 expression was
      also found in the cortical thick ascending limb of the loop of Henle (medullary
      rays and macula densa) in 50 of 53 cases. In the medulla, COX-2 expression was
      detected in the endothelial lining of the vasa recta in 52 cases and in the
      collecting ducts in 5 cases. These data show significant constitutive expression
      of COX-2 in normal kidney and underscore the need for caution in the use of COX-2
      selective inhibitors, especially on a long-term basis.

PMID- 15163024
TI  - Use of p63/P504S monoclonal antibody cocktail in immunohistochemical staining of
      prostate tissue.
AB  - Diagnosis of prostate needle biopsies can be challenging, particularly when the
      atypical areas of interest are very small. The utility of immunostains for high
      molecular-weight cytokeratin (34betaE12) to highlight prostatic basal cells in
      these cases is well established, and recent reports also document the utility of
      immunostains for p63 (a marker that stains the nuclei of prostate basal cells)
      for this purpose. Several investigators have demonstrated that immunostaining for
      P504S, a cytoplasmic protein that is overexpressed in a high percentage of
      prostate cancers and in many cases of high-grade prostatic intraepithelial
      neoplasia (PIN), can also be of use in the diagnosis of prostate biopsies.
      Because of the cytoplasmic localization of P504S and nuclear localization of p63,
      the authors hypothesized that a cocktail of these two antibodies might allow
      simultaneous demonstration of P504S and p63 using a single immunostain. In this
      report the authors describe the successful use of a cocktail of p63/P504S for
      immunohistochemical staining of prostate tissue. Two different staining
      approaches were investigated, with essentially identical results. This cocktail
      localizes P504S in the cytoplasm of prostate carcinoma cells and high-grade PIN
      and demonstrates the nuclei of prostatic basal cells, providing information on
      both the status of P504S and the presence or absence of basal cells with a single
      immunostain. This cocktail can be of great utility in the examination of
      diagnostically challenging prostate specimens.

PMID- 15163025
TI  - Common blue nevus of the uterine cervix: case report and review.
AB  - A case of common blue nevus of the uterine cervix in a 32-year-old woman is
      reported. This lesion was incidentally discovered in a hysterectomy performed for
      leiomyomas; in addition, a right ovarian benign serous cyst was found. The common
      blue nevus was restricted to the stroma of the endocervix and was characterized
      by clusters of dendritic melanocytes with benign histologic features. These cells
      were positive for melanin, S100, and HMB45. Electron microscopy disclosed
      melanosomes and premelanosomes. The differential diagnosis with other pigmented
      lesions, particularly with malignant melanoma, is emphasized.

PMID- 15163026
TI  - Investigations in renal failure.
AB  - The investigations which have been discussed above are by no means exhaustive.
      Since those with renal disease usually have multifactorial disease processes,
      many other specific investigations may be indicated. Although techniques and
      tests will continue to be updated and improved, it is hoped that by nurses
      understanding something of the current techniques used in renal investigations,
      they will be able to inform and reassure their patients reliably.

PMID- 15163028
TI  - On-line technique for producing substitution fluid in haemodiafiltration and
      haemofiltration.
AB  - When the kidneys are not able to fulfil their task anymore the individual reaches
      a situation known as End-Stage Renal Disease (ESRD). Haemodialysis may be carried
      out. In order to have a more efficient dialysis the treatment modes
      haemodiafiltration and haemofiltration are also in use. In these modes a
      substitution fluid is added to the bloodstream and continuously removed by the
      dialyser. However, these modes require large volumes of sterile fluids, 10 to 30
      litres for haemodiafiltration and 70 - 100 litres for haemofiltration. This fact
      has made these treatment modes expensive. The fluids have traditionally been
      produced by the pharmaceutical industry in five litre bags, but in bags not all
      solutions are stable or possible to produce, for instance when sodium bicarbonate
      is used as a buffer. Today sodium bicarbonate is the absolute predominant buffer.
      An alternative way of producing the fluids has to be found. In 1978 LW Henderson
      (1) described a technique using filtration to produce substitution fluid on-line
      i.e. preparing the fluid directly on site and giving it to the patient. Since
      then work has taken place in order to construct a system that is able to both
      mix, sterilise and administrate the substitution fluid in haemodiafiltration and
      haemofiltration. This work has resulted in dialysis machines with the feature to
      fulfil the task of producing sterile substitution fluid. On-line
      haemodiafiltration is carried out in dialysis clinics. There are approximately 65
      in Sweden, 1000 in Germany, 900 in Italy, 600 in France and 2500 in the US. The
      number of dialysis patients is around 1.000.000 worldwide and the increase is
      around 7 - 9% annually.

PMID- 15163027
TI  - Conventional blood sampling versus On-Line Clearance Monitoring.
AB  - On-line Clearance Monitoring (OCM) calculates the Kt/V during a dialysis session
      using a module incorporated into the Fresenius 4008 H/S haemodialysis machine
      (1). The method is based on repeated increments in dialysate sodium
      concentrations followed by measuring the change of dialysate sodium concentration
      after the dialysate has passed through the kidney. OCM is a patient friendly, non
      invasive and easy method for measuring Kt/V. Kt/V calculated on single-pool urea
      kinetics according to Daugirdas was compared to Kt/V measured by OCM in thirty
      stable patients on chronic haemodialysis. Patients were dialysed using a dialyser
      with either a high-flux polysulfone or a haemophane membrane. In four patients
      OCM was measured in ten consecutive sessions to assess the intra-individual
      variation in OCM. The calculated Kt/V was compared to Kt/Vocm in three patients
      at five consecutive dialysis sessions to measure the intra-individual
      correlation. A linear correlation was present between Kt/Vocal and Kt/Vac for
      both the polysulfone and haemophane membrane. Intra-individual Kt/Vocm showed
      very stable values with an average variation of less than 5%. Intra-individual
      correlation between calculated Kt/V and Kt/Vocm was high.

PMID- 15163029
TI  - Time distribution factors of hospital and home care among chronic haemodialysis
      patients.
AB  - Today, many studies are available that focus on haemodialysis; however studies on
      the time distribution factor involved are lacking. It is therefore important to
      study the distribution of time, taking into account outpatient care, inpatient
      care and home care. The aim of the study was to chart over a five-year period,
      the time distribution factors of hospital care and home care among chronic
      haemodialysis patients. The design of the study was descriptive, and the data
      material was drawn from a patient register (N = 61). The data analysis was
      performed by means of both descriptive and inferential statistics.

PMID- 15163030
TI  - Preventing cross infection of blood borne viruses on haemodialysis.
AB  - A chronic haemodialysis patient acquired hepatitis C. It was thought certain that
      this had occurred while dialysing in a satellite dialysis unit. The incident
      initiated a review of current measures in place to prevent the transmission of
      blood-borne viruses (BBV) on haemodialysis, with an analysis of current
      literature on the topic. It was found that the author's unit and several
      additional local units had no written protocols on prevention of BBV during
      haemodialysis, and methods of prevention were largely verbally communicated. A
      review of the literature gave conflicting opinions on the effectiveness of
      different measures to prevent cross-infection. Following the assessments and
      literature review, the appropriateness of certain preventative measures was
      looked at in more detail. A local protocol was subsequently developed and
      implemented at the author's Trust, which will significantly change practice in
      the haemodialysis unit.

PMID- 15163031
TI  - Evaluation of relationships between haemodialysis unit professionals.
AB  - This paper focuses on the dynamics of a workgroup in a nephrology and
      haemodialysis unit. Teamwork is indispensable in nephrology units, as it provides
      support and help to professionals but working closely together may also cause
      conflict and great strain. This study describes how much and in what way the
      anxiety and the relationship between these professionals influences their work,
      depending on skills and personal preferences among the staff. A questionnaire was
      used to analyse the following issues: stress, changes, routine, confrontation,
      comparisons, preferences, support, valuation, assertiveness, self-evaluation,
      technical competence, affiliation, motivation, work atmosphere and training.

PMID- 15163032
TI  - Counselling should be offered to people with end-stage renal failure.
AB  - Having a counsellor as a member of the multiprofessional team has made a positive
      contribution to the way in which people with end-stage renal failure manage their
      illness. This paper will show how families can be supported when someone close to
      them develops renal failure. A self-report questionnaire was sent to those who
      used the renal counselling service over a one-year period. Findings suggest that
      those who received a period of short-term counselling were able to cope more
      effectively with their illness and lifestyle changes and felt less stress as a
      result. The limitations of the evaluation will be discussed, however, we are not
      seeking to generalise our results but to describe our experience in our unit.
      This points to the value and necessity of having someone with the requisite
      skills, to offer people a place to talk about often difficult and painful
      emotions. In our professional opinion, all renal units should consider having a
      counsellor as part of an integrated approach to patient care.

PMID- 15163033
TI  - Renal anaemia--the patient experience.
AB  - In progress within the United Kingdom (UK) is the provision of a National Service
      Framework (NSF) for Renal Services. The Renal NSF aims to raise standards,
      provide equity of care, reduce variations in services and improve the health care
      of renal patients (1). The Renal NSF will be published in four distinct modules,
      each relating to a major area of renal care: effective delivery of dialysis,
      transplantation, prevention and primary care and alternative models of care.
      Taking into account the opinions of patients based on national surveys, has been
      recognised as an essential component in the modernisation programme of the NHS
      (2), and therefore this national survey represents consultation on current
      service provision. In 2000, the UK's National Kidney Federation (NKF) (supported
      by an educational grant from Amgen Ltd) conducted a postal survey of UK patients
      with renal diseases. This paper provides the patient perspective on anaemia
      management from this survey together with the implications for clinical practice
      for nurses and renal healthcare teams.

PMID- 15163034
TI  - How to evaluate organ donation: the quality programme in Tuscany.
AB  - The shortage of cadaveric organ donors imposes a severe limit on the number of
      patients who can benefit from transplantation. This paper describes a programme
      for evaluation and improvement of the organ donation process, which has been
      implemented in the hospitals of the Tuscany region, Italy. After analysing the
      first results it was found that there was great potential for growth, especially
      in those hospitals with neurosurgery where the weakest points of the process were
      detected The development of a quality improvement programme in cadaveric organ
      donation is an adequate and scientific method to detect where the problems in the
      process of organ donation lie. Ideally, the comparison of these data with those
      of other Italian or European regions should be very useful to plan adequate
      strategies to improve cadaveric organ donation.

PMID- 15163036
TI  - Reliability and repeatability of thermographic examination and the normal
      thermographic image of the thoracolumbar region in the horse.
AB  - REASONS FOR PERFORMING STUDY: Thermographic imaging is an increasingly used
      diagnostic tool. When performing thermography, guidelines suggest that horses
      should be left for 10-20 mins to 'acclimatise' to the thermographic imaging
      environment, with no experimental data to substantiate this recommendation. In
      addition, little objective work has been published on the repeatability and
      reliability of the data obtained. Thermography has been widely used to identify
      areas of abnormal body surface temperature in horses with back pathology;
      however, no normal data is available on the thermographic 'map' of the
      thoracolumbar region with which to compare horses with suspected pathology.
      OBJECTIVES: To i) investigate whether equilibration of the thermographic subject
      was required and, if so, how long it should take, ii) investigate what factors
      affect time to equilibration, iii) investigate the repeatability and reliability
      of the technique and iv) generate a topographic thermographic 'map' of the
      thoracolumbar region. METHODS: A total of 52 horses were used. The following
      investigations were undertaken: thermal imaging validation, i.e. detection of
      movement around the baseline of an object of constant temperature; factors
      affecting equilibration; pattern reproducibility during equilibration and over
      time (n = 25); and imaging of the thoracolumbar region (n = 27). RESULTS: A 1
      degrees C change was detected in an object of stable temperature using this
      detection system, i.e the 'noise' in the system. The average time taken to
      equilibrate, ie. reach a plateau temperature, was 39 mins (40.2 in the gluteal
      region, 36.2 in lateral thoracic region and 40.4 in metacarpophalangeal region).
      Only 19% of horses reached plateau within 10-20 mins. Of the factors analysed
      hair length and difference between the external environment and the internal
      environment where the measurements were being taken both significantly affected
      time to plateau (P<0.05). However, during equilibration, the thermographic
      patterns obtained did not change, nor when assessed over a 7 day period. A
      'normal' map of the surface temperature of the thoracolumbar region has been
      produced, demonstrating that the midline is the hottest, with a fall off of 3
      degrees C either side of the midline. CONCLUSIONS: This study demonstrates that
      horses may not need time to equilibrate prior to taking thermographic images and
      that thermographic patterns are reproducible over periods up to 7 days. A
      topographical thermographic 'map' of the thoracolumbar region has been obtained.
      POTENTIAL RELEVANCE: Clinicians can obtain relevant thermographic images without
      the need for prior equilibration and can compare cases with thoracolumbar
      pathology to a normal topographic thermographic map.

PMID- 15163035
TI  - Post insertion catheter care in peritoneal dialysis centers across Europe:
      results of the Post Insertion Project of the Research Board.
AB  - The EDTNA/ERCA survey of Post Insertion Catheter Care in Peritoneal Dialysis
      (PICC) was a project organised through the Collaborative Research Programme (CRP)
      of the EDTNA/ERCA. In this survey, data were collected from 54 participating
      centres in 20 countries. From this survey it became clear that there is no
      standardised approach to immediate post-catheter insertion treatment protocols.
      If we want to reduce technique failure of PD related to catheter failure, a first
      step will be to investigate the different policies used in Europe in order to
      evaluate the outcome results derived from different policies in post insertion
      catheter care.

PMID- 15163037
TI  - Treatment of chronic or recurrent proximal suspensory desmitis using radial
      pressure wave therapy in the horse.
AB  - REASONS FOR PERFORMING STUDY: Proximal suspensory desmitis (PSD) is diagnosed
      with increasing frequency in horses and radial pressure wave therapy (RPWT) is a
      widely used therapy for painful orthopaedic conditions in man and dogs. There
      are, however, few published data as to the outcome of its use in PSD. OBJECTIVE:
      To evaluate the use of RPWT in the treatment of chronic or recurrent PSD in the
      horse, an injury which carries a poor prognosis for return to athletic function
      with conservative management alone. HYPOTHESIS: RPWT and controlled exercise
      improves the prognosis of chronic or recurrent PSD in the horse when compared to
      previously published results of controlled exercise alone. METHODS: The use of
      RPWT in the management of chronic or recurrent proximal suspensory desmitis (PSD)
      was evaluated in 65 horses. Diagnosis was based on response to local analgesia,
      ultrasonography and radiography. Horses were classified according to severity of
      ultrasonographic lesions, whether fore- or hindlimbs were affected, and duration
      of lameness prior to diagnosis. Horses were treated 3 times at 2-week intervals
      and followed a controlled exercise programme; they were reassessed clinically and
      ultrasonographically 10-12 weeks after diagnosis, when further exercise
      recommendations were made dependent upon the animal's progress. RESULTS: Forty
      one percent of horses with hindlimb lameness and 53% with forelimb lameness were
      nonlame and returned to full work 6 months after diagnosis. The prognosis was
      significantly affected by the ultrasonographic grade at the time of diagnosis and
      by ultrasonographic evidence of resolution of the lesion in hindlimb cases.
      CONCLUSIONS: These findings, when compared to previously published results of
      treatment using controlled exercise alone, suggest that RPWT improves the
      prognosis for PSD in the hindlimb. POTENTIAL RELEVANCE: RPWT is a useful
      treatment modality for chronic or recurrent PSD when combined with controlled
      exercise. Further studies are required on the effect of RPWT employing histology
      and biomechanics in order to fully evaluate its use on equine tissues.

PMID- 15163038
TI  - Effects of stylopharyngeus muscle dysfunction on the nasopharynx in exercising
      horses.
AB  - REASONS FOR PERFORMING STUDY: Nasopharyngeal collapse has been observed in horses
      as a potential cause of exercise intolerance and upper respiratory noise. No
      treatment is currently available and affected horses are often retired from
      performance. OBJECTIVE: To determine the effect of bilateral glossopharyngeal
      nerve block and stylopharyngeus muscle dysfunction on nasopharyngeal function and
      airway pressures in exercising horses. METHODS: Endoscopic examinations were
      performed on horses at rest and while running on a treadmill at speeds
      corresponding to HRmax50, HRmax75 and HRmax, with upper airway pressures measured
      with and without bilateral glossopharyngeal nerve block. RESULTS: Bilateral
      glossopharyngeal nerve block caused stylopharyngeus muscle dysfunction and dorsal
      nasopharyngeal collapse in all horses. Peak inspiratory upper airway pressure was
      significantly (P = 0.0069) more negative at all speeds and respiratory frequency
      was lower (P = 0.017) in horses with bilateral glossopharyngeal nerve block and
      stylopharyngeus muscle dysfunction compared to control values. CONCLUSIONS:
      Bilateral glossopharyngeal nerve anaesthesia produced stylopharyngeus muscle
      dysfunction, dorsal pharyngeal collapse and airway obstruction in all horses.
      POTENTIAL RELEVANCE: The stylopharyngeus muscle is probably an important
      nasopharyngeal dilating muscle in horses and dysfunction of this muscle may be
      implicated in clinical cases of dorsal nasopharyngeal collapse. Before this
      information can be clinically useful, further research on the possible aetiology
      of stylopharyngeus dysfunction and dysfunction of other muscles that dilate the
      dorsal and lateral walls of the nasopharynx in horses is needed.

PMID- 15163039
TI  - Development and validation of a periarticular injection technique of the
      sacroiliac joint in horses.
AB  - REASONS FOR PERFORMING STUDY: Sacroiliac joint osteoarthritis has been recognised
      as a significant cause of poor performance in competition and racehorses.
      Reliable diagnostic tools are currently lacking. The diagnosis has been based
      typically on exclusion of other possible causes of poor performance, back pain
      and hindlimb lameness. OBJECTIVES: To develop a safe, reliable and minimally
      invasive periarticular or intra-articular injection technique of potential use
      for diagnosis and therapy of sacroiliac joint disease in horses. METHODS: Twenty
      six horses were used to develop and assess a medial approach to the sacroiliac
      joint with a 15 gauge, 25 cm long spinal needle. In Part I, the cadaveric study,
      the spinal needle was introduced cranial to the contralateral tuber sacrale and
      advanced along the medial aspect of the ipsilateral iliac wing until the dorsal
      surface of the sacrum was encountered. One ml methylene blue (MB) was injected in
      both sacroiliac joint regions of the sacropelvic specimens. The location of MB
      stained tissues relative to the sacroiliac joints was recorded after dissection
      and disarticulation of the sacroiliac joint. In Part II, the in vivo study, 18
      horses were used to validate the in vivo application of the sacroiliac joint
      injection technique. Horses were restrained in stocks and sedated in preparation
      for needle placement. One ml MB was injected bilaterally prior to euthanasia.
      Stained tissues were identified and recorded at necropsy. Successful joint
      injections were characterised as having MB located intra-articularly or < or = 2
      cm periarticularly from the sacroiliac joint margin and localised to the middle
      or caudal third of the sacroiliac joint. RESULTS: Intra-articular MB was not
      observed in any specimen. However, MB-stained tissue was identified
      periarticularly in all injection sites (n = 48). Based on the predetermined
      success criteria, 96% of the methylene blue depots were located at the middle or
      caudal third of the sacroiliac joint. Dye-stained tissue was located < or = 2 cm
      from the sacroiliac joint margins in 88% of the specimens. Median distance of the
      MB from the sacroiliac joint margins was 1.0 cm (range 0.2-3.8 cm). The overall
      success rate considering both location and distance of the MB-stained tissue
      relative to sacroiliac joint margins was 83% (40 of 48 joints). CONCLUSIONS: The
      injection technique provides a reliable, easy to perform and consistent access to
      the medial periarticular aspect of the sacroiliac joint. POTENTIAL RELEVANCE: The
      described injection technique has the potential for both diagnostic and
      therapeutic applications in the medical management of equine sacroiliac joint
      disease. Further investigation is necessary to evaluate clinical efficacy and
      potential adverse effects.

PMID- 15163040
TI  - Accuracy of diagnostic arthroscopy for the assessment of cartilage damage in the
      equine metacarpophalangeal joint.
AB  - REASONS FOR PERFORMING STUDY: There are many noninvasive diagnostic methods used
      for evaluating chronic progressive joint disease, but each has severe limitations
      in the detection of early articular cartilage damage. OBJECTIVES: To evaluate the
      accuracy of arthroscopy as a diagnostic method for the assessment of the severity
      of cartilage surface damage on the proximal articular margin of the equine first
      phalanx (P1). HYPOTHESIS: That arthroscopic assessment of the visible cartilage
      provides 1) a good indication of the integrity of the cartilage surface and 2) a
      good estimation of the status of the cartilage surface of the entire articular
      area of P1. METHODS: Arthroscopic examination of the dorsal pouch of the
      metacarpophalangeal joint was performed in the left front limbs of 74 slaughter
      horses (age 5 months to 23 years). The appearance of the visible cartilage of P1
      was scored by 2 independent arthroscopists, using the SFA arthroscopic grading
      system. The joints were dissected after completion of the arthroscopic procedure.
      The cartilage degeneration index (CDIP1) was determined and used as a
      quantitative measure for the overall degree of cartilage surface deterioration on
      the articular area of P1. Further, CDI values were determined for the dorsal
      articular margin of P1 (CDIdam), i.e. the area that can be visualised with
      arthroscopy. The CDIdam values were classified into 3 groups (CDIdam<25%, minor
      lesions; 25%<CDIdam<45%, moderate lesions; and CDIdam>45%, severe lesions).
      Differences between the 2 arthroscopists were evaluated statistically in a
      nonparametric test and Pearson correlation coefficients (r) with matching P
      values were determined for the correlations between SFA and CDIdam and between
      CDIP1 and CDIdam. The level of significance was set at P<0.05. RESULTS:
      Differences between SFA scores of the 2 arthroscopists were not significant (P =
      0.22). In the group of joints with minor cartilage changes, there was no
      correlation between SFA and CDIdam (r = 0.12; P = 0.71), but there was a
      significant correlation between CDIP1 and CDIdam (r = 0.95; P<0.01). In the group
      with moderate cartilage damage, there was an increase in correlation between SFA
      and CDIdam (r = 0.27; P = 0.09) and a decrease in the correlation between CDIP1
      and CDIdam (r = 0.48; P<0.01). In the group with severe cartilage changes, there
      was a significant correlation between SFA and CDIdam (r = 058; P<0.01), but no
      significant correlation between CDIP1 and CDIdam (r = 0.43; P = 0.06).
      CONCLUSIONS: Arthroscopic assessment of cartilage lesions on the proximal
      articular surface of P1 in joints with minor cartilage damage leads to an
      underestimation of the actual damage because proteoglycan depletion and light
      cartilage fibrillation cannot be detected arthroscopically. In cases with mild
      cartilage damage, the status of the cartilage surface of the visible area of P1
      is a good representation of the status of the entire articular surface. In cases
      with severe cartilage lesions, there is an overestimation of real damage. In such
      joints, the arthroscopic scoring system provides reliable information, but the
      visible area is not representative of the entire articular surface. POTENTIAL
      RELEVANCE: From a practical viewpoint, it can be stated that the arthroscopic
      grading of visible lesions on the equine P1 gives the best impression of overall
      cartilage damage in joints with moderately severe cartilage lesions. It should be
      realised, however, that this is the result of an underestimation due to the
      shortcomings of the grading system, which is neutralised by an overestimation due
      to the fact that the severity of lesions on the visible area of P1 is not
      representative for the entire articular surface.

PMID- 15163041
TI  - Routine castration in 568 draught colts: incidence of evisceration and omental
      herniation.
AB  - REASONS FOR PERFORMING STUDY: Castration is one of the most common routine
      surgical procedures performed in the horse, from which a number of potential
      complications can arise. We undertook a prospective evaluation of short-term
      complications associated with castration of draught colts over a 3-year period
      (1998-2000). OBJECTIVES: To compare castration complications in a large number of
      draught foals with previously published literature. METHODS: Five hundred and
      sixty-eight draught colts, age 4 or 5 months, were castrated in field conditions.
      Foals were observed for complications for 24 h post operatively. RESULTS: There
      was no significant difference in complication rates between open and closed
      surgical techniques. Inguinal/scrotal hernia rate was 4.6% (26/568) prior to
      surgery, and evisceration of the small intestine occurred in 4.8% (27/568). Foals
      observed to eviscerate underwent immediate surgical correction with an overall
      survival rate of 72.2% (13/18). Omental herniation was seen in 2.8% (16/568) of
      colts. CONCLUSIONS: This study showed no difference between the closed and open
      techniques of castration and the rate of omental herniation or evisceration. The
      evisceration rate in combination with the omental and presurgical herniation
      rates approached 12.2%, which is high enough to warrant further examination.
      POTENTIAL RELEVANCE: Future investigation should help to assess predisposing
      factors for evisceration. Regardless of the technique employed, herniation
      appears to pose a significant risk to draught foals undergoing castration.

PMID- 15163042
TI  - Detection of EHV-1 and EHV-4 DNA in unweaned Thoroughbred foals from vaccinated
      mares on a large stud farm.
AB  - REASONS FOR PERFORMING STUDY: A silent cycle of equine herpesvirus 1 infection
      has been described following epidemiological studies in unvaccinated mares and
      foals. In 1997, an inactivated whole virus EHV-1 and EHV-4 vaccine was released
      commercially in Australia and used on many stud farms. However, it was not known
      what effect vaccination might have on the cycle of infection of EHV-1. OBJECTIVE:
      To investigate whether EHV-1 and EHV-4 could be detected in young foals from
      vaccinated mares. METHODS: Nasal and blood samples were tested by PCR and ELISA
      after collection from 237 unvaccinated, unweaned foals and vaccinated and
      nonvaccinated mares during the breeding season of 2000. RESULTS: EHV-1 and EHV-4
      DNA was detected in nasal swab samples from foals as young as age 11 days.
      CONCLUSIONS: These results confirm that EHV-1 and EHV-4 circulate in vaccinated
      populations of mares and their unweaned, unvaccinated foals. POTENTIAL RELEVANCE:
      The evidence that the cycle of EHV-1 and EHV-4 infection is continuing and that
      very young foals are becoming infected should assist stud farms in their
      management of the threat posed by these viruses.

PMID- 15163043
TI  - Prevalence of superficial digital flexor tendonitis and suspensory desmitis in
      Japanese Thoroughbred flat racehorses in 1999.
AB  - REASONS FOR PERFORMING STUDY: Overstrain injuries to the superficial digital
      flexor tendon (SDFT) and suspensory ligament (SI) are among the most common
      musculoskeletal injuries which contribute to the considerable wastage of racing
      Thoroughbreds. Many epidemiological studies have demonstrated the prevalence of
      and risk factors for tendon injury when racing but have not included those
      injuries sustained during training. However, since tendon injury during training
      is seen commonly in clinical practice, it is appropriate to determine the overall
      prevalence of tendon injury sustained during both training and racing. OBJECTIVE:
      To determine the prevalence of overstrain injury to the SDFT and SL during
      training and racing among Thoroughbred flat racehorses in Japan in 1999. METHODS:
      A retrospective study was performed using a sample population of 10,262
      Thoroughbred racehorses. The medical information database of Thoroughbred
      racehorses registered by the Japan Racing Association (JRA) in 1999 was analysed
      for SDFT and SL overstrain injury diagnosed by a veterinarian employed by JRA
      during training and racing. Jump racehorses were excluded from this study.
      RESULTS: The prevalence of forelimb SDFT tendonitis and SL desmitis was 11.1%
      (1130 cases) and 3.61% (370 cases) of the population, respectively. In the
      hindlimb, there were 0.06% (6 cases) and 0.14% (14 cases), respectively. Risks of
      SDF tendonitis in the forelimb in 3-year-olds or older horses were significantly
      higher than in 2-year-olds. In contrast, the risk of SL desmitis in the forelimb
      at age 3 and 4 years was 2.23 and 2.11 times higher, respectively, than in 2-year
      olds, but this increased to 5.07 times in those age > or = 5 years. Entire males
      were at greater risk in comparison to females and geldings. CONCLUSIONS: The
      results suggest that the prevalence of SDF tendonitis and SL desmitis in the
      forelimb was associated with the horse's age and sex. The prevalence of SL
      desmitis increased further with age compared with SDF tendonitis, possibly
      reflecting a more rapid accumulation of degeneration in this structure. POTENTIAL
      RELEVANCE: The age-related risk demonstrated in this study provides further
      support that overstrain injuries are associated with accumulated degeneration.
      These data provide a valuable resource for further research into the aetiology of
      tendon injury in the racehorse.

PMID- 15163044
TI  - Screening of the equine intestinal microflora for potential probiotic organisms.
AB  - REASONS FOR PERFORMING STUDY: Probiotics have not been demonstrated to provide
      any beneficial health effects in horses, possibly because of improper selection
      of probiotic organisms. This study was designed to identify lactic acid bacteria
      of equine origin with predetermined beneficial properties which might make them
      useful as therapeutic probiotics. HYPOTHESIS: A small percentage of lactic acid
      bacteria that are native to the intestinal tract of horses possess properties
      that may be useful in the treatment and/or prevention of gastrointestinal disease
      in horses. METHODS: Faecal samples were collected from healthy mature horses and
      foals. Lactic acid bacteria were isolated and tested for the ability to grow in
      acid and bile environments, aerotolerance and in vitro inhibition of
      enteropathogens. One isolate that possessed these properties was administered
      orally to healthy mature horses and foals and gastrointestinal survival was
      assessed. RESULTS: Of the 47 tested organisms, 18 were deemed to be adequately
      acid- and bile-tolerant. All were aerotolerant. Four organisms markedly inhibited
      Salmonella spp. One isolate, Lactobacillus pentosus WE7, was subjectively
      superior and chosen for further study. It was also inhibitory against E. coli,
      moderately inhibitory against S. zooepidemicus and C. difficile and mildly
      inhibitory against C. perfringens. After oral administration, this isolate was
      recovered from the faeces of 8/9 (89%) foals and 7/8 (87.5%) mature horses.
      CONCLUSIONS: Lactobacillus pentosus WE7 possesses in vitro and in vivo properties
      that may be useful for the prevention and treatment of enteric disease in horses.
      POTENTIAL RELEVANCE: The beneficial in vitro and in vivo properties that L.
      pentosus WE7 possesses indicate that randomised, blinded, placebo-controlled
      efficacy studies are warranted.

PMID- 15163046
TI  - Comparison of pressure within the corpus spongiosum penis during urination
      between geldings and stallions.

PMID- 15163045
TI  - Arthroscopic debridement of subchondral bone cysts in the distal phalanx of 11
      horses (1994-2000).
AB  - REASONS FOR PERFORMING STUDY: Historically, there has been a consensus that
      conservative management of subchondral cystic lesions of the distal phalanx
      carries a poor prognosis. Surgical management has been advocated; however, there
      are no reports documenting its routine use and successful surgical treatment.
      OBJECTIVES: To describe arthroscopically-guided curettage of distal phalangeal
      subchondral cystic lesions (SCLs) and report the qualitative and quantitative
      results in 11 affected horses age 16-33 months. METHODS: Medical records of
      horses with previously treated lameness resulting from SCLs of the third phalanx
      were reviewed. Arthroscopic debridement of the SCLs was described. Follow-up
      information was obtained from race records and telephone contact with owners and
      trainers. The sign-rank test was used to compare performance of operated
      racehorses to that of unoperated siblings. RESULTS: Ten of the 11 horses (91%) in
      the study returned to athletic soundness after surgical treatment and had
      performance records similar to their siblings. CONCLUSIONS: Data show that
      arthroscopic debridement of distal phalangeal SCLs is a viable treatment for
      affected horses age 16-33 months and can result in a successful return to
      intended athletic performance. No horses younger than 16 months or older than 33
      months were treated and results in horses younger or older than this group may
      vary in success. POTENTIAL RELEVANCE: The description of treatment and approach
      used for arthroscopic curettage will increase awareness of this option and
      increase treatment options for this condition.

PMID- 15163047
TI  - Fractures and tendon injuries in National Hunt horses in training in the UK: a
      pilot study.

PMID- 15163048
TI  - What is your diagnosis? Ventricular tachycardia.

PMID- 15163049
TI  - Bone scintigraphy in the investigation of occult lameness in the dog.
AB  - 99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in
      14 dogs of different breeds after clinical lameness examination, radiography and
      synovial fluid analysis failed to localise lameness to a specific area of pain.
      The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc
      MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised
      positions with a low-energy all-purpose collimator. Confirmation of diagnosis was
      achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography,
      computed tomography and response to treatment. In seven cases, bone phase scans
      showed single elbow uptakes, in two cases unilateral limb uptake, and in one case
      each a single shoulder and tibia uptake; in three cases there was no increased
      uptake. Vascular and soft tissue phase images did not reveal additional
      information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid
      process, panosteitis and arthropathy was possible in nine cases. Skeletal
      pathology was ruled out in three normal scintigrams. In two dogs with unilateral
      uptake of multiple joints, no diagnostic benefit was gained from scintigraphy.
      The highly sensitive and relatively specific uptake allowed localisation and
      characterisation or exclusion of skeletal lesions in most dogs.

PMID- 15163050
TI  - Efficacy of combined cyclosporine A and ketoconazole treatment of anal
      furunculosis.
AB  - Cyclosporine A and ketoconazole were used as a combined therapy to treat 19 dogs
      with anal furunculosis. Complete resolution of all lesions was achieved in three
      to 10 weeks, but recurrences occurred in seven of the 19 dogs (36.8 per cent),
      with remission periods extending from one to six months for these dogs. Adverse
      effects of treatment included excessive hair loss, intermittent lethargy,
      vomiting and decreased appetite in some dogs, but none of the signs were
      considered serious. The results of treatment are comparable with, if not better
      than, the surgical alternatives. There is an approximate 70 per cent cost saving
      over the use of cyclosporine alone.

PMID- 15163051
TI  - Canine elbow dysplasia and primary lesions in German shepherd dogs in France.
AB  - Five hundred and twenty German shepherd dogs were screened for elbow dysplasia.
      The following primary lesions were analysed: joint incongruity (JI), fragmented
      medial coronoid process (FCP), osteochondrosis or osteochondritis of the medial
      humeral condyle and ununited anconeal process (UAP). Three radiographic views
      were used for each joint to achieve a definitive diagnosis. The prevalence of
      elbow dysplasia was 19.4 per cent. The most frequent lesion was JI (16.3 per
      cent), followed by FCP (11.3 per cent). UAP was diagnosed rarely (1.1 per cent).
      Combinations of lesions were very frequent (42.2 per cent of the dysplastic
      elbows). Although these results may be biased due to prescreening of dogs with
      UAP, it should be highlighted that JI and FCP occur frequently in German shepherd
      dogs and are probably the most common primary lesions of elbow dysplasia,
      although they have been under-reported until now.

PMID- 15163052
TI  - Prolonged interval between parturition of normal live pups in a bitch.
AB  - On day 64 after artificial insemination, a six-year-old primiparous briard bitch
      whelped three live pups between 05.00 and 08.00. It was presented at 11.00 on the
      same day with failure to complete parturition. On ultrasound examination, a
      normal live fetus was observed and the bitch was treated with oxytocin three
      times during the day (1.0, 2.0 and 2.0 iu intramuscularly), with no effect. The
      following day, a higher dose of oxytocin (5.0 iu) was administered
      intramuscularly at 11.00, after a uterine ultrasound examination confirmed
      viability of the fetus. At 18.00 of the same day, the bitch whelped the fourth
      normal live pup, 37 hours after initiation of parturition and 34 hours after
      expulsion of the last fetus. Effectiveness of oxytocin and normal versus
      prolonged parturition due to uterine inertia are discussed.

PMID- 15163053
TI  - Dermatitis and lymphadenitis resembling juvenile cellulitis in a four-year-old
      dog.
AB  - A four-year-old, entire male toy poodle was presented with a two-and-a-half-week
      history of ocular discharge progressing to periorbital alopecia, depigmentation,
      alopecia and ulceration around the muzzle. There was also a haemorrhagic
      discharge from the ears, pyrexia, lethargy and generalised lymphadenopathy. The
      clinical, cytological, bacteriological and histopathological findings were
      consistent with a diagnosis of dermatitis resembling juvenile cellulitis in an
      adult dog. Glucocorticoid therapy led to rapid resolution of the clinical signs
      and the dog has remained in remission for two years after cessation of treatment.

PMID- 15163054
TI  - Multicentric lymphoma in a dog after cyclosporine therapy.
AB  - An 11-year-old, neutered male German shepherd dog was presented with perianal
      ulceration and fistulas. A clinical diagnosis of anal furunculosis was made, and
      the dog was treated with cyclosporine and ketoconazole. The perianal lesions
      resolved. However, after four weeks of therapy the dog developed multicentric
      lymphoma. Complete remission was achieved with combination chemotherapy
      (Wisconsin-Madison protocol). Cyclosporine administration is associated with an
      increased risk of development of lymphoma in humans and a similar increased risk
      might be expected in dogs. Although a causative relationship between cyclosporine
      administration and the development of lymphoma cannot be proven in this case, it
      is possible that cyclosporine therapy may have contributed to lymphomagenesis. As
      the use of cyclosporine in small animals is increasing, further work is required
      to substantiate and quantify the proposed increased risk.

PMID- 15163055
TI  - Trilostane treatment of bilateral adrenal enlargement and excessive sex steroid
      hormone production in a cat.
AB  - A 14-year-old neutered female cat was presented for the investigation of
      aggression and male-type behaviour. Bilateral adrenal enlargement together with
      elevated plasma concentrations of oestradiol and testosterone were identified,
      with no evidence of hypercortisolaemia. These findings are similar to the
      syndrome of hyperadrenocorticism recognised most commonly in ferrets. The cat was
      treated for six months with the enzyme inhibitor drug, trilostane, and showed a
      moderate improvement in clinical signs.

PMID- 15163056
TI  - Spinal nephroblastoma in a crossbreed dog.
AB  - A three-year-old, male crossbreed dog presented with progressive hindlimb
      paresis. Magnetic resonance imaging revealed an intramedullary spinal cord lesion
      of 1.5 cm diameter at the levels of the first and second lumbar vertebrae.
      Following surgical excision of the mass, there was resolution of the neurological
      signs. Twelve months later, hindlimb paresis was again evident. A second surgical
      procedure restored ambulatory status for a further five months before signs
      recurred and the dog was euthanased. A diagnosis of spinal nephroblastoma was
      made on the basis of signalment, lesion location and histopathological analysis
      of biopsy specimens.

PMID- 15163057
TI  - Value before cost when screening for canine hip dysplasia.

PMID- 15163058
TI  - Pet passports to replace PETS certificates.

PMID- 15163059
TI  - Hospital acoustic pollution: seeking "the sound of silence".

PMID- 15163060
TI  - The self-locating peritoneal catheter.

PMID- 15163061
TI  - Long thrice weekly hemodialysis: the Tassin experience.

PMID- 15163062
TI  - Mass transfers in a fluidized bed bioreactor using alginate beads for a future
      bioartificial liver.
AB  - Fluidized bed bioreactor with alginate beads may be an alternative to hollow
      fiber cartridge to host hepatocytes for bioartificial liver purposes. After the
      bioreactor design and the characterization of fluid mechanics, the present study
      was aimed at analyzing bi-directional mass transfers of calibrated species
      between external fluid and empty beads. Static (batch) and dynamic (fluidized bed
      bioreactor) experimental conditions were analyzed. A simple modelling approach
      permitted the definition of mass transfer coefficients. The motion of beads
      within the bioreactor clearly enhanced mass transfer kinetics, but did not alter
      the amount exchanged. The shear enhanced diffusion coefficient for VitB12 was 20
      times higher in the fluidized bed bioreactor than under batch conditions, proving
      the efficiency of such a device.

PMID- 15163063
TI  - Efficacy of immunoadsorbent devices for maintaining hepatic function in ex vivo
      direct xenogenic hemoperfusion.
AB  - We have developed a new system for direct xenogenic hemoperfusion of a
      bioartificial liver support system adopting two types of immunoadsorbent devices.
      In this study, we compared the efficacy of each immunoadsorbent device in
      maintaining porcine hepatocyte function during 3 h perfusion treatment in a
      canine liver failure model. Suppression of humoral immunity by the immunoglobulin
      adsorber prevented immunogenic hepatocyte injury more effectively, and the system
      showed higher hepatic function when compared with suppression of cell-mediated
      immunity by the leukocyte adsorber. However, single use of immunoglobulin
      adsorber was less effective in reducing patients' systemic ammmonia levels and
      modulating the Fischer's ratio compared with the case of combined use of both
      immunoadsorbent devices. These results suggest that suppression of humoral
      immunity was of primary importance in preventing immunogenic hepatocyte injury,
      however the adsorption of leukocytes may have a synergic effect on maintaining
      hepatocyte function in direct xenogenic hemoperfusion.

PMID- 15163064
TI  - Influence of serum from rats with fulminant hepatic failure on hepatocytes in a
      bioartificial liver system.
AB  - Fulminant hepatic failure (FHF) is a life-threatening condition marked by many
      excessively increased unmetabolized toxins and growth factors. Recently developed
      bioartificial liver (BAL) systems containing hepatocytes can be used to treat
      patients with FHF However, the behavior of these hepatocytes on exposure to FHF
      serum in vitro remains unclear. In the present study, we used FHF rat models and
      the sera from these rats (i.e., FHF serum) contained elevated inflammatory
      cytokines (TNF-alpha, IL-1beta, and IL-6), HGF, and TGF-beta1. In addition,
      1x10(8) hepatocytes were harvested from the livers of inbred rats and incubated
      with microcarrier beads. Four hours later, the hepatocyte-coated beads were
      inoculated into a hollow-fiber module (=BAL system). FHF serum or normal control
      serum circulated for 6 hours through the BAL system. Expressions of mRNA for
      albumin, GST A1, CYP 1A2, OTC and c-fos were investigated by RT-PCR, and PCNA
      staining was performed before and after perfusion. The expressions of albumin,
      GST A1, and CYP 1A2 mRNAs were markedly decreased, whereas those of OTC and c-fos
      were modestly decreased. PCNA positive cells were low and showed no difference
      between FHF and normal serum-exposed hepatocytes. In conclusion, the exposure of
      hepatocytes to hypercytokinemia, including inflammatory cytokines and positive
      and negative growth factors, caused a loss in liver specific functions. This
      environment also failed to facilitate hepatocyte regeneration.

PMID- 15163065
TI  - Reduced systemic heparin dose with phosphorylcholine coated closed circuit in
      coronary operations.
AB  - In this prospective cohort study we addressed the clinical impact of a reduced
      anticoagulation protocol on the hospital outcome of patients undergoing coronary
      revascularization with cardiopulmonary bypass. 364 consecutive low to moderate
      risk patients scheduled for elective isolated coronary operations were admitted
      to the study. 184 patients (Control Group) received conventional open circuits
      and full systemic anticoagulation (target activated clotting time 480 seconds);
      180 patients (Intraoperative ECMO group) received closed, phosphorylcholine
      coated circuits and a reduced systemic heparin dose (target activated clotting
      time 320 seconds). Patients of the Intraoperative ECMO group had less requirement
      for allogeneic blood products (odds ratio 0.55, 95% confidence interval 0.34
      0.92, p = 0.02), a significant containment of blood loss (374 +/- 278 mL vs. 463
      +/- 321 mL in Control group, p = 0.005) a lower postoperative peak serum
      creatinine levels (1.19 +/- 0.48 mg/dL vs. 1.41 +/- 0.94 mg/dL in Control group,
      p = 0.048), and a significant lower rate of severe morbidity (odds ratio 0.27,
      95% confidence interval 0.09-0.81, p = 0.02). A reduction of systemic
      anticoagulation is feasible with a non-heparin-bonded, closed biocompatible
      circuit, and results in a significant improvement of the outcome of low to
      moderate risk coronary patients.

PMID- 15163066
TI  - EPO or not-EPO? An evidence based informed consent.
AB  - BACKGROUND: Informed consent is crucial in therapeutic choices; however, the
      forms presented to patients are often locally developed and information may not
      be homogeneous. OBJECTIVE: To prepare an evidence-based model for informed
      consent, applied in the case of erythropoietin therapy (EPO) as a teaching tool
      for medical students. METHODS: Methodological tools of Evidence-Based Medicine
      (EBM) were developed within the EBM Course in the Medical School of Torino,
      Italy, as problem solving and patient information tools (5th year students work
      in small groups under the supervision of statisticians, epidemiologists and
      experts of internal medicine--nephrology in this case). RESULTS: Methodological
      and ethical problems were identified: in the pre-dialysis field, evidence from
      randomized clinical trials (RCT) is scant; how to use evidence gathered in
      dialysis? How to deal with implementation? How with the mass media? Do we need to
      discuss the drug choice with the patients? How to deal with rare and severe side
      effects?). The "evidence" was searched for on Medline/Embase, by using key-words
      and free terms. About 680 papers were retrieved and screened. Forms available on
      the Internet were retrieved and a general scheme was drawn: it included 5 areas:
      title, aim and targets (patients and family physicians); search strategies and
      updating; pros and cons of therapy; alternative options; open questions.
      CONCLUSIONS: EBM may offer valuable tools for systematically approaching patient
      information; the inclusion of this kind of exercise in the Medical School EBM
      courses may help enhance the awareness of future physicians of the correct
      communication with patients.

PMID- 15163067
TI  - Charlson Comorbidity Index is a predictor of outcomes in incident hemodialysis
      patients and correlates with phase angle and hospitalization.
AB  - BACKGROUND: The adjustment of comorbidity is important in international
      hemodialysis comparisons. The aim of this study is to verify if it is possible to
      use the Charlson Comorbidity Index (CCI), in an Italian population of incident
      hemodialysis patients from the Campania region as outcome predictors. A similar
      proposal has already been made for an American population of incident patients in
      peritoneal dialysis. METHODS: The data for this study come from the Uremic
      Registry of Campania taken in the year 2001. This is an observational study in
      which demographic, comorbid, laboratory, treatment and insurance data were
      collected in 111 dialysis units (70%) in Campania. We evaluated 515 hemodialysis
      incident patients who were hemodialyzed in Campania between January 1 and
      December 31, 2001. The study was restricted to patients who had already undergone
      90 days of hemodialysis. The duration of this study was 15 months. Charlson
      Comorbidity Index was performed. In 128 patients (24.8%) BIA measurements were
      performed after dialysis. STATISTICS: We used Student's t test for unpaired data
      and Cox proportional model to analyze predictors of mortality. The variables
      analyzed were age at start of hemodialysis, sex, CCI, hemoglobin, diabetes,
      hypertension, albumin, days of hospitalization. The statistically significant
      variables, analyzed initially by univariate analysis, were chosen for
      multivariate analysis. We considered p < 0.05 statistically significant. RESULTS:
      A total of 515 patients (M = 316, F = 199) (age: 63.62 +/- 15.35 years) presented
      with the following diseases: NO diagnosed in 93 patients (19%), GN in 64 (13%) IN
      in 42 (99%), Hereditary in 55 (11%), Vascular in 66 (14%), Diabetes in 135 (28%),
      others in 30 (6%). Hemoglobin levels were 10.71 +/- 1.51 g/dL and albumin was
      3.79 +/- 0.54 g/dL. The days of hospitalization for the population studied were
      3364/year. After the study, 75 patients died and the overall mortality rate was
      11.65/100 patient/years. Univariate analysis shows that there are significant
      differences calculated for age (median value 73 and 65 years, respectively for
      non-survivers and survivers), BMI (median value and 22 and 24 kg/m2,
      respectively), Hb (median value 9.5 and 11 g/dL, respectively), Albumin (median
      value 3.5 and 3.8 g/dL, respectively), days of hospitalization (median value 8
      and zero days, respectively), CCI (median value 6 and 4 score, respectively,
      phase angle (median value 3.3 and 4 degree, respectively). The mortality rates
      (100 dialysis years) by the CCI score: the mortality rate was zero for patients
      with a CCI of 3; and it increased to approximately 60% of patient years with a
      CCI score of 6 or greater. The linear correlation between CCI and phase angle in
      living (y = 18.90 x -3.83; R2 = 0.56) and in the dead (y = 13.01 x -1.87; R2 =
      0.29). DISCUSSION: We found that CCI is a strong predictor of mortality in
      incident HD patients as has also been indicated in PD patients; CCI correlates
      with phase angle calculated from Bioelectrical Impedance Analysis and this last
      factor can be used in the following examinations; several days of hospitalization
      are a very important determinant in the survival in hemodialysis patients.

PMID- 15163068
TI  - LDL-apheresis in acute anterior ischemic optic neuropathy.
AB  - Acute anterior ischemic optic neuropathy (AION) is a disabling disease which
      impairs visual function. Standard treatment is unable to affect the outcome and
      the visual damage persists. We describe the case of a 64-year-old patient
      affected by AION, whose only known risk factor was hypercholesterolemia. After a
      first onset of involvement of the right eye (RE), the patient presented four
      weeks later with an analogous episode affecting the left eye (LE). Since standard
      treatment, started at involvement of the RE, had not yielded any beneficial
      effect, the patient underwent three sessions of LDL apheresis. The scotomatous
      portion of the visual field reduced even after the first session, there was
      further improvement after the third, and after six months the condition remained
      stable. Corrected vision improved from 2/10 to 6/10 after the third session. LDL
      cholesterol and fibrinogen decresade after the third session from 239 mg/dL to 31
      mg/dL and from 289 mg/dL to 92 mg/dL, respectively. In conclusion, thanks to its
      effect of antagonizing hemorheologic disorders of the ocular microcirculation,
      LDL apheresis seems to be an efficacious treatment of AION, especially in
      patients suffering from hypercholesterolemia.

PMID- 15163070
TI  - The legal protection of test subjects in clinical trials of medicinal products
      for human use in the European Union.
AB  - On the international as well as on the level of the European Union a legal
      framework has been developed on the protection of test subjects has been
      developed. In 2000, the Declaration of Helsinki, issued by the World Medical
      Association, was revised and the previous distinction between therapeutic and non
      therapeutic trial situations has been eliminated. Non-therapeutic trials that
      only aim at the progress of scientific knowledge and do not benefit the patient
      are now admissible. This is not to the benefit of the position of the test
      subject and most certainly not when the test subject should be given special
      protection. The question arises what this recent revision means for the group of
      incompetent adult patients in clinical trials on medicinal products (hereinafter
      called drugs) in the European Union (EU). This group needs special protection.
      Also relevant are national and international legal frameworks and the protection
      offered by informed consent procedures and screening by ethics committees and
      member states' competent authorities.

PMID- 15163069
TI  - Extracorporeal albumin dialysis in a patient with primary sclerosing cholangitis:
      effect on pruritus and bile acid profile.

PMID- 15163071
TI  - The relationship between health care and mass media in Polish law.
AB  - The purpose of this presentation is to analyse the relations between: medical
      professionals (physicians, nurses, pharmacists) and health institutions (their
      managers), and, press and other media, from the point of view of Polish law. In
      this respect the medical professional or institution is situated between health
      law and press law--sometimes without realising the common problems of both, such
      as the problem of access to information versus personal privacy or the question
      related to medicine-press contacts in the advertising of professionals,
      institutions and pharmaceuticals. In this paper I shall attempt to examine the
      interdisciplinary areas of current Polish law.

PMID- 15163073
TI  - Patients' rights in New Zealand: complaints resolution and quality improvement.
AB  - "Patients' rights" has become a familiar catchword in western countries in recent
      years. In New Zealand the Office of the Health and Disability Commissioner was
      established in 1994 to promote and protect patients' rights. The Commissioner
      also facilitates the resolution of complaints relating to the infringement of
      patients' rights as set out in the Code of Health and Disability Services
      Consumers' Rights. Victims of medical misadventure in New Zealand are compensated
      through a no-fault, state-funded rehabilitation and compensation scheme. The
      regulatory environment is rehabilitative rather than punitive. This framework is
      consistent with a systems approach to reducing errors and improving patient
      safety, and the Commissioner seeks to use the resolution of individual complaints
      as a tool for improving the quality of care throughout the health care system.

PMID- 15163072
TI  - Embryonic stem cell research: terminological ambiguity may lead to legal
      obscurity.
AB  - National regulation on embryonic stem cell research in the European Union is
      ambiguous, due to a lack of consistent scientific terminology as exemplified by
      the Dutch Embryos Act. To force a breakthrough in this ethically dubious research
      topic, a more careful use of terminology would be in the interest of both the
      scientific community and the lawmakers, in order to avoid terminology becoming
      associated with research or applications for which it is inappropriate. Therefore
      I will first clarify the technological possibilities in an age of biological
      control. Secondly, we will critically analyse the statements of the European
      Convention on Human Rights and Biomedicine concerning embryo research and
      cloning. The Convention prohibits human reproductive cloning but does not take a
      clear position on so-called therapeutic cloning. Finally, we will give an
      overview of the most recent legislative initiatives within the European Union on
      this matter.

PMID- 15163074
TI  - Tissue banking, patient rights, and confidentiality: tensions in law and policy.
AB  - The collection, storage and analysis of tissue samples, including genetic data,
      has become an increasingly common part of biomedical research. Though there are
      many scientific justifications for the creation of tissue and DNA databanks, the
      storage and use of human tissue continues to create legal dilemmas. In this
      paper, the impact and relevance of existing common law principles are reviewed.
      It is noted that the Canadian common law rules covering consent and
      confidentiality may create challenges for the research community. Emerging health
      information legislation does, however, create a somewhat more lenient research
      environment, largely because these laws allow, in some circumstances, research on
      identifiable health information without consent. Nevertheless, conflicts between
      existing common law, research ethics policy and new health information
      legislation illustrate profound policy dilemmas created by research involving
      storage and use of tissue and genetic material.

PMID- 15163075
TI  - Patients' rights versus family rights: the situation in Italy.
AB  - The authors, on the basis of Italian legislative and deontological regulation,
      discuss the problems which are faced in reconciling rights and ethical
      considerations involving patients and their families. In Italy, with the
      exception of parents and guardians (for minors and those incapable of consent),
      there is no family member that Italian law recognises for the purposes of giving
      consent in the name of another. In all cases, contact with the family must be
      authorised by the patient in accordance with Law 675/1996 regarding privacy.
      However, in some situations having the advice of a member of the family can be
      useful, as it can be of benefit to know the will, tacitly or expressly
      demonstrated, of the patient. Nonetheless, their opinion cannot be binding on the
      doctor and he or she is not obliged to request it. Ethically, this usually
      demands evaluation of almost every case.

PMID- 15163076
TI  - Reassessing "Jacob's case": a serial killer re-examined after ten years.
AB  - The current study re-examines an exceptional case of a serial killer incarcerated
      since a decade ago. "Jacob" is the first serial killer apprehended in Israel. His
      known actions were committed during the eighties of the last century, and
      continued for eleven years. The victims were elderly individuals, including both
      his parents. Shortly after incarceration he became overtly schizophrenic and
      underwent five hospitalisations. The case is re-examined in view of changes, both
      in the perpetrator's diagnosis and criminal legislation. Was Jacob doomed to
      become a serial killer, or could his fate be avoided through early professional
      intervention? Were the killings presenting symptoms of a psychotic or pre
      psychotic phase? Should he be eligible for a retrial? What would have been his
      position with the current law in view of the new 300A(a) clause ("Reduced
      Punishment") of the Israeli Criminal Code? Could he ever be released back to the
      community? These are some of the questions to be addressed.

PMID- 15163077
TI  - Abortion in Islamic countries--legal and religious aspects.
AB  - The debate over abortion is still controversial as ever. As one of every four
      people in the world is of the Muslim religion, it is important to learn more
      about the Islamic point of view toward this dilemma in medical ethics. The first
      part of this paper gives a general view of the sources of Islamic law and
      discusses modern developments in Islamic medical ethics regarding abortion. The
      second part focuses on the legal aspects of abortion in different Islamic states,
      dealing with the need to supply solutions to women who for different reasons wish
      to abort and at the same time enact laws that would not contradict Islamic
      principles. A study of three Muslim states (Egypt, Kuwait and Tunisia)
      demonstrates three different approaches toward legalizing abortion--a
      conservative approach, a more lenient approach, and a liberal one--all within
      Islamic oriented states. This leads to a conclusion that a more liberal attitude
      regarding abortion is possible in Islamic states, as long as traditional
      principles are taken into account.

PMID- 15163078
TI  - Rape as a legal indication for abortion: implications and consequences of the
      medical examination requirement.
AB  - A number of countries adopt abortion laws recognizing rape as a legal ground for
      access to safe abortion service. As rape is a crime, these abortion laws carry
      with them criminal and health care elements that in turn result in the
      involvement of legal and medical expertise. The most common objective of the laws
      should be providing safe abortion services to women survivors of rape. Depending
      on purposes of a given abortion law, the laws usually require women to undergo a
      medical examination to qualify for a legal abortion. Some abortion laws are so
      vague as to result in uncertainties regarding the steps health personnel must
      follow in conducting medical examination. Another group of abortion laws do not
      leave room for regulation and remain too rigid to respond to changing socio
      economic circumstances. Still others require medical examination as a
      prerequisite for abortion. As a result, a number of abortion laws remain on the
      books. The paper attempts to analyze legal and practical issues related to
      medical examination in rape cases.

PMID- 15163079
TI  - Impact of the European Clinical Trials Directive on academic clinical research.
AB  - With the adoption of the Clinical Trials Directive it was Europe's intention to
      make the performance of multi-national clinical trials in Europe easier through
      the harmonization of the regulatory procedures. As the Directive was mainly
      conceived to facilitate the performance of multi-national clinical trials to
      develop new drugs, it is to be determined to what extent academic clinical trials
      will be concerned by the Directive and more importantly what will be its impact
      on daily academic clinical research. Contrary to several national regulations the
      scope of the Directive is very large only excluding non-interventional trials.
      This implies that most of the academic clinical trials will be concerned by the
      Directive. Besides the handling of the regulatory procedures in the different
      countries, issues related to insurance, labeling requirements and provision of
      the investigational medical products will expose the academic sponsor to
      additional administrative and financial challenges that will have to be handled
      appropriately, as the academic sponsors will be controlled by Inspectors
      regarding their compliance with the new regulations to come.

PMID- 15163080
TI  - Organ and tissue transplantation in Greece: the law and an insight into the
      social context.
AB  - Advances in biological sciences and medicine have revolutionized current practice
      and opened new horizons. Tissue and organ transplantation is a miracle and an
      action of love and sacrifice for the sake of fellow human beings. Organ
      transplantation has been commonplace over the last decade but Greece still
      remains the lowest numerically among European countries in this field because of
      the lack of organ donation although it is highest in traffic accidents. Despite
      this, the legal framework regulating transplantation was enacted late in
      comparison to other European countries, and was not the only obstacle to the
      development of organ donation. Several other factors such as philosophy, culture,
      traditional and religious attitudes, lack of public information and lack of the
      relevant social fabric, have all contributed to the current sad situation. This
      article aims to present a critical view on the evolution of the legal framework
      in the field of tissue and organ transplantation in Greece. Issues that still
      deter organ donation are discussed along with an insight into the current
      situation in the Greek social context in order to make a constructive
      contribution to future perspectives.

PMID- 15163081
TI  - Epilepsy: a question of ethics--why undertake such a project and the methodology
      adopted.

PMID- 15163082
TI  - Epilepsy and confidentiality: ethical considerations.

PMID- 15163083
TI  - Alternative dispute resolution and disputes concerning physicians' practices or
      services.

PMID- 15163084
TI  - Negotiating in the public interest: considerations for health negotiators acting
      on behalf of government (NABG).
AB  - It is asserted that what distinguishes government negotiations from those
      conducted within solely the private sector is the role played by the public
      interest in the former. This is a subject area that has not received a great deal
      of academic attention. Direct interviews with government negotiators in the
      health field are used to explore the nature and expression of the public interest
      in public policy negotiations. The information drawn from the interviews is then
      set against a review of the literature on the public interest and government
      negotiations. Many of the negotiators interviewed differed as to what constituted
      the public interest. On the basis of the interviews conducted, it appears that
      the public interest acts to restrain the government from applying its power
      during negotiations regardless of the level of awareness the negotiators have of
      this phenomenon. The research conducted suggests that government negotiators,
      without explicit direction but with a deep understanding of the culture within
      the government, work with both the public and private interests of the government
      when they conduct a negotiation.

PMID- 15163085
TI  - An analysis of a health professions appeal board--should a mediational style of
      hearing matters be adopted?
AB  - The Ontario Health Professions Board is a statutory Board that carries out a
      supervisory function and review function of certain matters arising from twenty
      three health professions in the province. This paper examines the board, how it
      functions, and the nature and type of disputes, which come before it. Having
      regard to key concepts in the areas of conflict analysis and process design, the
      paper critically discusses whether the Board ought to adopt a mediational style
      of hearing matters. The conclusions are that there are very real dangers that the
      current practices of the Board may contribute to conflict rather than resolve it,
      that there is no legal impediment to the Board adopting a mediational style of
      hearing matters, and that such an approach would contribute to the Board
      effectively carrying out its statutory functions.

PMID- 15163086
TI  - Using therapeutic jurisprudence and preventive law to examine disputants' best
      interests in mediating cases about physicians' practices: a guide for medical
      regulators.
AB  - Therapeutic jurisprudence (TJ) and preventive law (PL) are used as two
      theoretical perspectives from which to examine the best interests of parties in
      mediation because of a dispute about a physician's practice. The focus is
      mediation provided by and/or for the medical regulator. The paper reviews the
      literature on TJ and PL, and their relationship to mediation, and demonstrates
      how medical regulators could benefit by working within a framework reflecting
      both these perspectives providing it does not involve an egregious matter. A TJ
      and PL framework would be of particular value in identifying cases for mediation
      and in evaluating resolutions to mediated disputes.

PMID- 15163087
TI  - Institutionally sponsored mediation and the emerging medical trust movement in
      the U.S.
AB  - This essay identifies the bias that institutional sponsorship of medical
      mediation introduces and the probability that such bias undermines the ability of
      such mediation programs to generate trust by patients in physicians and health
      care institutions. Based on data from an emerging medical trust movement in the
      U.S., the essay argues that institutionally sponsored medical mediation programs
      are missing an opportunity to reap the economic benefits of promoting trust
      through the use of classic mediation techniques. It also identifies new tools for
      measuring trust that have been created as part of the emerging movement, and it
      explains how those tools can be used to confirm the economic value of classical
      mediation while remaining free of much of the bias that appears to plague current
      institutionally sponsored medical mediation programs.

PMID- 15163088
TI  - Neuropsychiatric problems in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is an autosomal dominant disorder characterized by
      abnormal cellular differentiation and proliferation, as well as abnormal neuronal
      migration. It is a disease affecting multiple organ systems and typically has
      brain involvement, causing severe disabilities. This article reviews the
      literature of the commonly associated neuropsychiatric complications, including
      mental retardation, autism-like features, and other behavior problems, which are
      discussed in the context of the neuropathology and epilepsy observed in tuberous
      sclerosis complex. The potential pathogenesis of neuropsychiatric problems is
      explored, including links to the genetics, neuropathology, neurotrophins, and
      epilepsy factors associated with tuberous sclerosis complex. Treatment of
      neuropsychiatric symptoms, including autism-like features, attention deficits,
      and sleep disorders, is also discussed.

PMID- 15163089
TI  - Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a
      randomized study.
AB  - Childhood tuberculous meningitis is associated with serious long-term sequelae,
      including mental retardation, behavior disturbances, and motor handicap. Brain
      damage in tuberculous meningitis results from a cytokine-mediated inflammatory
      response, which causes vasculitis and obstructive hydrocephalus. Thalidomide, a
      potent tumor necrosis factor alpha inhibitor, was well tolerated and possibly
      showed some clinical benefit in children with tuberculous meningitis during a
      pilot study. The purpose of the present study was to assess the effect of
      adjunctive thalidomide in addition to standard antituberculosis and
      corticosteroid therapy on the outcome of tuberculous meningitis. Thalidomide (24
      mg/kg/day orally) or placebo was administered in a double-blind randomized
      fashion for 1 month to patients with stage 2 or 3 tuberculous meningitis. The
      study was terminated early because all adverse events and deaths occurred in one
      arm of the study (thalidomide group). Thirty of the 47 children enrolled received
      adjunctive thalidomide, of whom 6 (20%) developed a skin rash, 8 (26%) hepatitis,
      and 2 (6%) neutropenia or thrombocytopenia. Four deaths (13%) occurred in
      patients with very severe neurologic compromise at baseline; two deaths were
      associated with a rash. Motor outcome after 6 months of antituberculosis therapy
      was similar in the two groups, even though the thalidomide group showed greater
      neurologic compromise on admission. In addition, the mean IQ of the two treatment
      groups did not differ significantly (mean IQ thalidomide group 57.8 versus mean
      IQ control group 67.5; P = .16). These results do not support the use of
      adjunctive high-dose thalidomide therapy in the treatment of tuberculous
      meningitis.

PMID- 15163090
TI  - Mitochondrial DNA deletion in a child with megaloblastic anemia and recurrent
      encephalopathy.
AB  - A 3 1/2-year-old boy presented with megaloblastic anemia and recurrent episodes
      of severe lactic acidosis and coma. At age 4 years, he developed sepsis and died;
      postmortem examination failed to show any gross abnormality in any tissue.
      Biochemical analysis of muscle showed decreased activities for all respiratory
      chain enzymes except complex II. Muscle histochemistry revealed diffuse
      cytochrome c oxidase deficiency. Southern blot analysis of mitochondrial DNA from
      muscle, liver, and blood showed a heteroplasmic single mitochindrial DNA deletion
      of 2.4 kb, which removed the genes for cytochrome c oxidase I and II and the
      transfer ribonucleic acid genes for serine and aspartic acid. Single large-scale
      deletions in mitochondrial DNA have been associated with Pearson's syndrome,
      Kearns-Sayre syndrome, and progressive external ophthalmoplegia. This patient's
      presentation is unusual and suggests an overlap between Pearson's syndrome and
      Kearns-Sayre syndrome.

PMID- 15163092
TI  - Unique clinical phenomenology can help distinguish primary from secondary
      generalized seizures in children.
AB  - The physical manifestations a seizure produces provide critical information. It
      is assumed that all generalized convulsions are ostensibly the same, regardless
      of whether they are primary or secondary generalized seizures. We undertook a
      pilot study to determine if the clinical phenomenology of secondary generalized
      seizures in children with epilepsy is different from classic descriptions of
      generalized tonic-clonic convulsions. A data capture sheet was created and
      applied to the video-electroencephalographic (EEG) records of 64 secondary
      generalized seizures from 13 children with intractable and/or refractory
      epilepsy. Many features of secondary generalized seizures were different from
      traditional descriptions of generalized convulsions. In 100% of cases, the mouth
      either remained open or repeatedly opened and closed rather than slamming shut.
      In 77% of cases, a variety of late motor activities were seen to occur after the
      seizure activity had ceased and the EEG record was quiet. The clinical features
      of a generalized convulsion in a child, especially mouth opening and late motor
      events, can be useful in establishing the origin as either focal or primary
      generalized.

PMID- 15163091
TI  - Factors associated with poor control in partial complex epilepsy.
AB  - To evaluate the predictive factors of response to anticonvulsant therapy in
      children with complex partial epilepsy, we studied prospectively 74 children and
      adolescents suffering from this type of epilepsy. All children were prospectively
      followed for at least 2 years after the beginning of anticonvulsant therapy. At
      the end of follow-up, the children were subdivided into two groups according to
      the frequency of seizures: group A, children who were seizure free in the last
      year, and group B, children with at least six seizures in the previous year.
      Children with a poor response to anticonvulsant therapy had a more frequent
      personal history of neonatal seizures, an interval of less than 6 months between
      the first and the second seizures, and persistent abnormal electroencephalograms
      than the seizure-free patients and were often treated with polytherapy.

PMID- 15163093
TI  - Prevalence of epilepsy in Turkish children between the ages of 0 and 16 years.
AB  - The aim of this cross-sectional study was to determine the prevalence of epilepsy
      in Turkey among children between the ages of 0 and 16 years. The study population
      consisted of 24,773,569 children living in Turkey. Because the prevalence of
      childhood epilepsy is reported to be 0.001 to 1% in the literature, the sample
      size was determined as 48,260, with 0.05 error type I and 0.10 error type 2
      (power 0.90), and the effect size was 2. With the cluster sampling method,
      samples were selected from cities, towns, districts, and villages, and 46,813
      (97%) children were reached. The study questionnaire contained sections with
      individual informational questions and questions for the selection of suspected
      epilepsy cases and physical examination results. The epilepsy classification was
      designed according to the classification of the International League Against
      Epilepsy (ILAE). The prevalence of epilepsy was determined as 0.8%; 55.2% of the
      subjects with epilepsy were grouped as generalized, 39% as partial, and 5.8% as
      unidentified. Age, place of residence, route of delivery, place of delivery, and
      social and economic status had no statistically significant effect on the
      development of epilepsy. Male gender, preterm, and post-term delivery increased
      the risk of developing epilepsy. Early diagnosis and treatment of epilepsy, as
      well as the education of health workers and families, are very important.

PMID- 15163094
TI  - Reduced brain size and gyrification in the brains of dyslexic patients.
AB  - Dyslexia is a specific learning disability that affects the way in which a person
      acquires reading skills. The pathologic substrate of the condition has been
      debated in the literature. Conclusions from postmortem studies remain
      controversial because series have been based on few and often ill-characterized
      cases. The present article expands on one of the reported neuropathologic
      findings in dyslexia, that is, wider minicolumns. Measurements were made of
      magnetic resonance images in a series of 16 dyslexic and 14 age- and sex-matched
      controls. Dyslexic patients had significantly smaller total cerebral volume (P =
      .014) and reduced gyrification index (P = .021). No changes were noted in
      cortical thickness, the ratio of gray to white matter, or the cross-sectional
      areas of the corpus callosum and medulla oblongata. The findings, although not
      conclusive, are in keeping with a minicolumnar defect in dyslexia. The decreased
      gyrification and preserved cortical thickness can alter the information
      processing capacity of the brain by providing a greater degree of cortical
      integration at the expense of a slower response time. The article also emphasizes
      the contrast between findings in dyslexia and in autism.

PMID- 15163095
TI  - What ever happened to developmental Gerstmann's syndrome? Links to other
      pediatric, genetic, and neurodevelopmental syndromes.
AB  - Developmental Gerstmann's syndrome is a neurodevelopmental disorder infrequently
      described in the literature. The limited literature might result from controversy
      surrounding developmental Gerstmann's syndrome as a "true syndrome."
      Developmental Gerstmann's syndrome requires a tetrad of symptoms: left-right
      confusion, finger agnosia, dyscalculia, and dysgraphia, with constructional
      dyspraxia often included as a fifth symptom. The etiology of developmental
      Gerstmann's syndrome is unknown, but several hypotheses have been proposed, and
      none have been conclusively confirmed. Based on the paucity of recent research on
      developmental Gerstmann's syndrome, individuals who meet the criteria for the
      disorder could be given other diagnoses. A clustering of neuropsychologic
      features across other seemingly related disorders suggests that the
      conceptualization of the tetrad of symptoms traditionally associated with
      developmental Gerstmann's syndrome more appropriately reflects soft signs that
      are commonly associated with a number of other neurodevelopmental disorders.
      Thus, although developmental Gerstmann's syndrome is of historical interest to
      neurodevelopmental specialists, there appears to be no basis for considering this
      disorder as a unique syndrome.

PMID- 15163096
TI  - Further analysis of the impact factors and submission information for the Journal
      of Child Neurology.
AB  - Now in its nineteenth volume year, the Journal of Child Neurology continues its
      preeminence among child neurology journals. The Institute of Scientific
      Information impact factor value for the year 2002 of 1.338 places the Journal of
      Child Neurology seventy-first in rank among the 138 clinical neurology journals.
      Since 1998, the rejection rate for manuscripts has been nearly 25%, with more
      than half of the accepted manuscripts originating in North America. In its first
      18 volumes, the journal published 2144 items as listed in the PubMed database of
      the National Library of Medicine, and for 2003, the PubMed database indexed 176
      published items from the Journal of Child Neurology.

PMID- 15163097
TI  - Effective treatment with oxcarbazepine in paroxysmal kinesigenic choreoathetosis.
AB  - Paroxysmal kinesigenic choreoathetosis is often responsive to anticonvulsants
      such as carbamazepine and phenytoin. We report a boy with paroxysmal kinesigenic
      choreoathetosis, which is dramatically relieved by oxcarbazepine even after
      unsatisfactory treatment with carbamazepine and other medications.

PMID- 15163098
TI  - Polyoma nephropathy and progressive multifocal leukoencephalopathy in a renal
      transplant recipient.
AB  - Progressive multifocal leukoencephalopathy is a progressive and ultimately fatal
      white-matter disease of the brain that is associated with polyomavirus infection.
      It is uncommon in the general population, and even in the immunosuppressed
      patient, who is inherently at greatest risk for active infection with the virus,
      it is rare. The causative agent in progressive multifocal leukoencephalopathy, JC
      virus, has become increasingly important in recent years as its role in
      nephropathy in the renal transplant recipient has become better understood. We
      present a young renal transplant patient who developed nephropathy with renal
      biopsy changes consistent with polyomavirus lesions and then developed mental
      status changes and was diagnosed with progressive multifocal leukoencephalopathy.

PMID- 15163100
TI  - Infection as a cause of age-related morbidity and mortality.

PMID- 15163099
TI  - Frontal lobe seizures and uveitis associated with acute human parvovirus B19
      infection.
AB  - We report a 5-year-old girl who developed repeated episodes of behavioral
      alterations shortly after human parvovirus B19 infection and uveitis. Video
      electroencephalographic study demonstrated that these brief episodes were frontal
      lobe seizures. Seizures responded promptly to antiepilepsy medications. Further
      diagnostic testing did not reveal any rheumatologic disorders. Human parvovirus
      B19 infections in children are more commonly associated with febrile seizures and
      meningoencephalitis. Our case demonstrates that, rarely, it may be associated
      with the development of partial epilepsy.

PMID- 15163102
TI  - Lung infections and aging.
AB  - Respiratory tract infections are the leading cause of death due to infectious
      disease in the elderly. Many factors, especially waning immune responses and the
      onset of age-associated organ dysfunction, likely account for an increase in
      susceptibility to respiratory tract infection in the elderly, and morbidity and
      mortality rates are substantially greater for the elderly when outcomes are
      compared to that of younger individuals. The presence of underlying disease
      states such as chronic obstructive pulmonary disease (COPD) or other organ system
      disease further increases the likelihood of developing severe pneumonia in the
      elderly population, and the frail elderly, particularly when institutionalized in
      chronic care facilities, are at high risk for developing severe and recurrent
      pneumonia. This article will discuss various factors associated with advanced age
      that predispose the elderly to respiratory infections and summarize current
      approaches to treatment and prevention.

PMID- 15163101
TI  - Follicular dendritic cells in aging, a "bottle-neck" in the humoral immune
      response.
AB  - Senescence leads to the appearance of atrophic follicular dendritic cells (FDCs)
      that trap and retain little immune complexes (IC), generate few memory B cells,
      and induce a reduced number of germinal centers (GC). Deficiencies in antibody
      responses to T cell dependent exogenous antigens such as pneumonia and influenza
      vaccines may reflect intrinsic FDC defects or altered FDC-B cell interactions. We
      recently studied antigen handling capacity and co-stimulatory activity of old
      FDCs and determined age-related changes in the expression or function of
      FcgammaRII or CR1 and 2 on FDCs. Here, we present an overview of FDC function in
      recall responses with known deficiencies in FDCs and GC development. Then, we
      review our recent work on aged FDCs and discuss age-related changes in molecular
      interactions between FDCs and B cells. We also discuss the causes underlying the
      impaired humoral immune response with respect to age-related molecular changes in
      FDC and B cell interactions. In vitro evidence suggests that FcgammaRII on aged
      FDCs is regulated abnormally and this in turn might cause the development of a
      defective FDC-network (reticulum) that retains few ICs, promotes ITIM signaling,
      prevents B cell proliferation and GC formation, and antibody production.

PMID- 15163103
TI  - Skin infections and ageing.
AB  - Elderly individuals have an increased susceptibility to skin infections due to
      age-related anatomical, physiological and environmental factors. The types of
      organisms that cause primary skin and soft tissue infections are diverse, and
      include bacterial, viral and fungal pathogens as well as parasites. In the
      elderly, these infections and infestations may present with atypical signs and
      symptoms or may complicate underlying chronic skin disorders. Clinical features,
      investigations and management of the following important and common skin
      infections are described in more detail: cellulitis, erysipelas, necrotizing
      fasciitis, impetigo, folliculitis, furunculosis and carbunculosis, erythrasma,
      herpes zoster and postherpetic neuralgia, herpes simplex, warts, molluscum
      contagiosum, dermatophytosis of the skin, hair and nails, candidiasis, and
      scabies. Treatment should be based on the results of the appropriate diagnostic
      tests. Correct diagnosis and therapy of skin infections lead to satisfactory
      outcome in the majority of elderly patients.

PMID- 15163104
TI  - Impact of nutritional status and nutrient supplements on immune responses and
      incidence of infection in older individuals.
AB  - With advancing age there is a progressive decline in immune responses although
      this is not inevitable. The impairment in immunocompetence is noticeable as early
      as 35-40 years in many individuals. At the same time, some persons even in the
      80s may show a vigorous immune system comparable with that of the young adult.
      Nutrient deficiencies are frequent in older populations. A variety of nutrients
      are affected: zinc, iron, beta-carotene, Vitamins B6, B12, C, D and E, ad folic
      acid. The causal interaction between nutritional deficiencies and impaired
      immunity has been known in children; a similar relationship has been postulated
      in the elderly. In the last 25 years, many studies employing different designs
      have examined the role of diet, nutritional status, and nutrient supplements in
      the immune responses of older individuals. Some nutrients, for example zinc and
      Vitamin E, have been shown to increase selected immune responses but have not
      been beneficial in terms of reduction in infectious morbidity. A growing
      consensus indicates that the use of a multinutrient containing optimum amounts of
      essential trace elements and vitamins is likely to result in enhanced immune
      responses and reduction in the occurrence of common infections. These findings
      have considerable fundamental, clinical and public health significance.

PMID- 15163105
TI  - Infectious agents and age-related neurodegenerative disorders.
AB  - chlamdAs with other organ systems, the vulnerability of the nervous system to
      infectious agents increases with aging. Several different infectious agents can
      cause neurodegenerative conditions, with prominent examples being human
      immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of
      the central nervous system (CNS) typically have a relatively long incubation
      period and a chronic progressive course, and are therefore increasing in
      frequency as more people live longer. Infectious agents may enter the central
      nervous system in infected migratory macrophages, by transcytosis across blood
      brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses
      and lipid rafts are important sites at which infectious agents may enter neurons
      and/or exert their cytotoxic effects. Recent findings suggest the possibility
      that infectious agents may increase the risk of common age-related
      neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's
      disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can
      be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and
      influenza promote damage to neurons during aging, there is no conclusive evidence
      for a major role of these pathogens in neurodegenerative disorders. In the case
      of stroke, blood vessels may be adversely affected by bacteria or viruses
      resulting in atherosclerosis.

PMID- 15163106
TI  - Epidemiology of extra-articular manifestations in rheumatoid arthritis.
AB  - Extra-articular RA (ExRA) includes a wide variety of disease manifestations.
      Although rheumatologists in general are aware that such events are clinically
      important, the heterogeneity of available data, including discrepancies in case
      definitions, has complicated constructive discussions on this aspect of the RA
      disease phenotype. In recent years, there has been a growing recognition of the
      importance of co-morbidity in patients with RA. ExRA manifestations are not
      uncommon, explain excess mortality in RA and are predicted by smoking and
      autoantibodies. Further studies of the mechanisms underlying these associations
      are likely to be important in improving our understanding of the systemic nature
      of RA. This article discusses the methodological issues involved in the study of
      ExRA manifestations, presents suggested criteria that have been used in clinical
      studies, and reviews important surveys of the epidemiology of extra-articular RA.

PMID- 15163107
TI  - Prevalence and incidence of shoulder pain in the general population; a systematic
      review.
AB  - OBJECTIVE: To investigate the incidence and prevalence of shoulder complaints in
      the general population. METHOD: A systematic review of the literature was
      conducted. Medline, Embase, and Cinahl were searched for relevant studies.
      RESULTS: Eighteen studies on prevalence and one study on incidence met the
      inclusion criteria. Incidence figures of 0.9-2.5% were found for different age
      groups. Prevalence figures differed from 6.9 to 26% for point prevalence, 18.6
      31%, for 1-month prevalence, 4.7-46.7% for 1-year prevalence and 6.7-66.7% for
      lifetime prevalence. Prevalence rates decreased when the case definition was
      restricted, in terms of duration of pain or the presence of limited movements,
      and increased when the location for pain was enlarged. CONCLUSION: The reported
      prevalence figures on shoulder complaints diverged strongly. Health professionals
      and policymakers who estimate the amount of medical care needed and related costs
      should be aware of the variations in prevalence rate and the underlying reasons
      for these differences.

PMID- 15163108
TI  - Improvement of refractory rheumatoid arthritis after depletion of B cells.
AB  - OBJECTIVE: B cells are involved in the pathogenesis of rheumatoid arthritis (RA).
      To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an
      open label study has been performed using the B-cell depleting anti-CD20 antibody
      rituximab. METHODS: Five patients with refractory RA were treated weekly with
      four infusions of rituximab (375 mg/m2) alone, or in combination with ongoing
      methotrexate (MTX). Patients were followed for at least 44 weeks and monitored
      for safety and tolerability of treatment. RESULTS: Treatment could be performed
      without serious side effects and resulted in peripheral B-cell depletion lasting
      between 36 weeks up to > 1 year. The follow-up revealed no significant treatment
      associated side effects. At 22 weeks, 4/5 patients showed a significant
      improvement (> 1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all
      patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another
      patient still had a sustained response, and three patients showed slowly
      increasing disease activity (mean DAS28 of the remaining four patients: Week 0:
      6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin
      levels, rheumatoid factor levels decreased parallel to disease activity.
      CONCLUSION: In patients with refractory RA, B-cell depletion with rituximab is
      safe and well tolerated. A reduction of disease activity could be observed, which
      eventually deteriorated after B-cell repopulation. The findings give more
      evidence for B-cell targeted therapies in RA.

PMID- 15163109
TI  - Relationship between the area of cartilage shown on the magnetic resonance
      imaging middle-slice image of the medial and lateral tibial cartilages with
      cartilage volume and grade of osteoarthritis over time.
AB  - OBJECTIVE: Knee cartilage volume measurement requires significant time and
      training. Simplifying the measurement may improve feasibility. We investigated
      whether the area of cartilage shown on the middle slice of the medial and lateral
      tibial cartilages on sagittal MRI correlates with radiological features of
      osteoarthritis (OA), cartilage volume, and longitudinal change in cartilage
      volume. METHODS: One hundred and seventy-three subjects (normal and
      osteoarthritic), who had serial magnetic resonance imaging (cartilage volume
      measured) and baseline weight-bearing antero-posterior radiographs of the same
      knee were examined. RESULTS: In the lateral compartment, with increasing grade of
      OA there was a significant reduction in cartilage area. In the medial
      compartment, this was true for medial joint-space narrowing (after adjusting for
      gender). There was a moderate to strong association between cartilage area and
      volume, especially in those with early or no OA. However, when change over time
      was examined, the strength of these relationships was weak. CONCLUSION: Our data
      suggests that cartilage area may provide a simple surrogate measure of cartilage
      volume, in cross-sectional studies, after adjustment for gender: especially in
      subjects with early disease. However, before it can be widely used, further
      investigation will be required.

PMID- 15163110
TI  - Ultrasonography as a tool for diagnosis, guidance of local steroid injection and,
      together with pressure algometry, monitoring of the treatment of athletes with
      chronic jumper's knee and Achilles tendinitis: a randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: The diagnosis of Achilles and patella tendinitis has until recently
      been based on clinical examination, and treatment with local steroid injection
      has been given blindly. This is the first randomized, double blind, placebo
      controlled study of local steroid injection in athletes with chronic tendinitis,
      which used ultrasonography to increase diagnostic accuracy, to guide the correct
      placement of local steroid and, conjunctively with pressure algometry, to
      objectify and monitor the results of treatment. METHOD: Forty-eight athletes each
      with severe symptomatic tendinitis of a patellar (24) or Achilles tendon (24) for
      more than 6 months, whose conditions were confirmed ultrasonographically, and who
      all failed conservative treatment (rehabilitation) were included in this double
      blind, placebo-controlled study and treated with three ultrasonographically
      guided peritendinous injections of steroid or placebo. RESULTS: The conditions of
      only one-third of the referred athletes with clinically suspected tendinitis were
      confirmed by ultrasonographic examination. The ultrasonographically guided
      peritendinous injection of steroid had a significant effect in reducing pain and
      thickening of tendons. CONCLUSION: Ultrasonography should be used in the future
      to assure precise diagnosis and to guide the peritendinous injection of steroid
      in chronic Achilles and patella tendinitis. Ultrasonography and pressure
      algometry are recommended as objective methods for monitoring the effect of
      treatment. Ultrasonographically guided injection of long-acting steroid can
      normalize the ultrasonographic pathological lesions in the Achilles and patellar
      tendons, and has a dramatic clinical effect but when combined with aggressive
      rehabilitation with running after a few days, many will have relapse of symptoms
      within 6 months.

PMID- 15163111
TI  - Daily activities and hand function in women with scleroderma.
AB  - OBJECTIVE: To give a detailed description of hand function and the ability to
      perform daily activities among patients with systemic sclerosis. METHODS: Thirty
      patients with scleroderma answered a self-administered activities of daily living
      (ADL) questionnaire. Hand function was estimated with respect to hand mobility,
      dexterity, and grip force. Perceived symptoms were reported on a visual analogue
      scale (VAS), and skin thickness was assessed by means of the modified Rodnan skin
      score. RESULTS: Finger flexion and extension were the most impaired aspects of
      hand mobility. Dexterity was on average reduced to 68-80%, and grip force to 46
      65% compared with values for healthy persons. The predominant self-perceived
      problem was Raynaud's phenomenon, whereas pitting scars/ulcers were perceived as
      the least problem. Activities building on hand and arm function were harder to
      perform than activities depending on lower limb function. Raynaud's phenomenon,
      stiffness, grip force, and dexterity were factors with the strongest associations
      with ADL difficulties. Assistive devices and alternative working methods improved
      ADL ability. CONCLUSION: Impaired hand function was related to ADL difficulties
      and the use of assistive devices improved ADL. This emphasizes the importance of
      treatments that improve hand function and of testing ergonomic tools.

PMID- 15163112
TI  - Predominant inhibition of Th1 cytokines in New Zealand black/white F1 mice
      treated with FK506.
AB  - The T-helper 1/T-helper 2 (Th1/Th2) cell balance was examined in 6-month-old New
      Zealand black/white F1 (B/WF1) mice treated with an immunosuppressive agent,
      FK506. The survival rate of mice treated with 10 mg/kg/day of FK506 was 7/8,
      while that of those treated with 2.5 mg/kg/day was 5/8, and 4/8 after treatment
      for 8 weeks with placebo. Proteinuria, which was already positive in all mice
      before the treatment, in the seven of eight mice treated with 10 mg/kg/day
      remained mildly positive (< or = 1+), while seven of eight mice treated with 2.5
      mg/kg/day and six of eight mice treated with the placebo showed severe
      proteinuria (> or = 2+). Pathological changes in the kidneys of mice treated with
      10 mg/kg/day of FK506 were less severe than in mice treated with the placebo or
      2.5 mg/kg/day of FK506. Expression of mRNA was unchanged for all cytokines
      determined in the groups treated with 2.5 mg/kg/day of FK506 or placebo. In
      contrast, expression of mRNA for interleukin (IL)-2, and interferon (IFN)-gamma
      was suppressed, while that for IL-4 and IL-10 was not suppressed in the group
      treated with 10 mg/kg of FK506. The serum levels of IgG-class anti-DNA
      antibodies, which had been elevated before the treatment, were suppressed-
      especially in the IgG2a subclass--and the deposition of IgG2a and IgG2b in the
      glomeruli was reduced in the group treated with 10 mg/kg/day of FK506 compared
      with the other groups. These findings suggest that an improvement in the lupus
      nephritis of 6-month-old B/WF1 mice induced by FK506 might be associated with a
      predominant inhibition of Th1 cytokine.

PMID- 15163113
TI  - Limited Wegener's granulomatosis presenting with complete heart block.
AB  - Complete heart block associated with Wegener's granulomatosis (WG) is rare, and
      has not previously been reported with 'limited' WG. The case of a 36-year-old man
      who presented with complete heart block due to 'limited' WG [positive cytoplasmic
      antineutrophil cytoplasmic antibodies (c-ANCA) on indirect immunofluorescence,
      positive serum antibodies to proteinase-3, and inflammatory sinus disease seen on
      computerized tomography (CT) without renal or pulmonary involvement] is
      presented. In addition, a gallium-scan fused with a myocardial perfusion scan and
      cardiac magnetic resonance imaging (MRI) suggested focal inflammation near the
      atrioventricular (AV) node.

PMID- 15163114
TI  - Sinus histocytosis with massive lymphadenopathy (Rosai-Dorfman disease) in a
      patient with primary Sjogren's syndrome.
AB  - Sinus histocytosis with massive lymphadenopathy is a rare disease that has been
      described by Rosai and Dorfman. It is characterized by massive, cervical
      lymphadenopathy, with extranodal manifestations in about 40% of patients. It
      occurs as a distinct entity, never associated with other diseases, and in most
      cases the prognosis is good. Lymphadenopathy is also a frequent sign of patients
      with primary Sjogren's syndrome (SS), usually associated with disease activity or
      concurrent infection. However, excessive lymphadenopathy in SS patients is a sign
      of lymphoproliferative disorder development. In this report, we describe a
      patient with primary SS, and excessive lymphadenopathy and splenomegaly who
      developed Rosai-Dorfman disease, and we discuss the possible
      aetiopathophysiological mechanism linking these two entities.

PMID- 15163115
TI  - An unusual presentation of familial Mediterranean fever with prolonged hip pain
      and amyloidosis.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent self-limiting attacks of joint, chest and abdominal
      associated with fever. We present an unusual case of FMF with prolonged arthritis
      and amyloidosis. Familial Mediterranean fever should be considered in the
      differential diagnosis of prolonged hip pain, even in the absence of symptoms or
      signs of FMF.

PMID- 15163116
TI  - The relationship between insulin-like growth factor-II gene Apa I polymorphism
      and rheumatoid arthritis.

PMID- 15163118
TI  - Up-regulation of c-FLIPshort and reduction of activation-induced cell death in T
      cells from patients with Type 1 diabetes.
AB  - AICD of T-cells is an efficient way of removing activated T-lymphocytes. In this
      study we investigated the molecular basis of AICD upon reactivation in peripheral
      T-lymphocytes from newly diagnosed T1DM patients and age-matched healthy
      controls. In an in vitro model system, PHA-stimulated T-cells, upon prolonged
      culture in IL-2, acquire a sensitive phenotype to Fas-mediated apoptosis. This
      phenomenon is less pronounced in T1DM T-cells. Moreover, the restimulation of
      activated T-cells via TCR/CD3 and/or via CD28 inhibits Fas-mediated apoptosis in
      T1DM in comparison to control T-cells. After Fas triggering, the generation of
      the active sub-units of caspase-8 is significantly reduced in T1DM T-cells
      restimulated via TCR/CD3 and/or CD28. In parallel, we found that the amount of c
      FLIPshort protein is significantly increased in the DISC only in T1DM T-cells
      restimulated via TCR/CD3 and via CD28. These data suggest that increased levels
      of c-FLIPshort may prevent recruitment of pro-caspase-8 in T1DM CD3-treated T
      cells and provide new insight into the molecular mechanisms of apoptosis
      resistance in stimulated T-cells from T1DM patients.

PMID- 15163117
TI  - The influence of oral insulin on the development of autoimmune diabetes in NOD
      mice fed a hypoallergenic diet.
AB  - BACKGROUND: Autoimmune diabetes can be prevented in animal models by
      hypoallergenic diets. Moreover, in animal models, oral administration of insulin
      can suppress the development of autoimmune diabetes and clinical trials on
      prevention of human Type 1 diabetes by oral administration of insulin are already
      taking place. However, it has been reported that autoimmune diabetes can be
      induced by oral administration of an auto-antigen (insulin), and great caution is
      therefore warranted when applying the oral tolerance approach to prevent Type 1
      diabetes. AIM: To evaluate the effect of orally administered insulin on the
      development of autoimmune diabetes in non-obese diabetic mice fed a
      hypoallergenic diet. METHODS: Four groups of mice were fed regular mouse chow
      (group 1, control mice), hypoallergenic diet, using the hydrolyzed infant formula
      Pregistimil (group 2), and Pregistimil with oral insulin (4 U/l of drinking
      water, group 3; and 8 U/l of drinking water, group 4). RESULTS: At 210 days of
      age, 11/20 (55%) mice in group 1 developed diabetes. In contrast, none of the
      mice from the Pregistimil-fed groups (0/16, 0/14, 0/17) developed the disease
      (p<0.001). The incidence of infiltrated islets and the severity of insulitis, at
      age 90 days, was significantly lower in mice fed with the hypoallegenic diet than
      in controls (p=0.028). CONCLUSIONS: In NOD mice fed a diet that prevents the
      development of diabetes, oral insulin supplementation appears to be safe, since
      it does not promote the development of clinical diabetes.

PMID- 15163119
TI  - Serum magnesium levels in non-diabetic offspring of patients with Type 2 diabetes
      mellitus.
AB  - A tendency for magnesium deficiency in patients with diabetes mellitus is well
      established, which probably results from glycosuria-related hypermagnesiuria,
      nutritional factors or hyperinsulinaemia. Hypomagnesaemia is probably a secondary
      event but it can also lead to insulin resistance itself. The offspring of
      patients with Type 2 diabetes mellitus (T2DM) are at increased risk of developing
      diabetes and several metabolic abnormalities of the disease. The aim of this
      study was to determine if serum total magnesium levels in healthy offspring of
      T2DM patients underwent alterations and their relationship to indicators of
      glucose homeostasis. The sample consisted of two groups: 30 healthy offspring
      with at least one diabetic parent, and 30 age-matched healthy subjects with no
      family history of T2DM. None of the participants was on a diet. The mean serum
      magnesium concentration was 1.070 +/- 0.059 mmol/l in offspring and 1.075 +/-
      0.084 mmol/l in controls (p=0.66). There was no statistically significant
      correlation between serum magnesium levels and parameters of glucose homeostasis
      in offspring. Our results support the conclusion that total serum magnesium
      probably has no relationship with the main indicators of glucose homeostasis in
      offspring of T2DM patients and is not likely to be a fundamental risk factor for
      the development of insulin resistance.

PMID- 15163120
TI  - Influence of two polymorphisms of the tumoral necrosis factor-alpha gene on the
      obesity phenotype.
AB  - Several populational-based studies have suggested an association between tumoral
      necrosis factor-alpha (TNF-alpha) polymorphisms and obesity-related phenotypes.
      Therefore, this study aimed at assessing the situation (frequency and associated
      phenotype) of two TNF-alpha common polymorphisms in a Spanish population. In a
      case-control design study, a group of Spanish subjects (n=313) were genotyped for
      the TNF-alpha G/A -308 and -238 polymorphisms. Obese subjects (cases) were
      compared with lean individuals (controls) according to body mass index (BMI;
      cases: BMI >30 kg/m2, controls: BMI <25 kg/m2). Waist-to-hip ratio, body
      composition and some metabolic indicators were assessed. The frequency of the 
      308A allele (0.14) and -238A allele (0.09) was similar to those previously
      reported in other Caucasian populations. Interestingly, cases with the -308A
      allele of the TNF-alpha gene have significantly higher hip and waist
      circumferences (p<0.05), BMI (p<0.01) and body fat mass (p<0.05) values than
      obese individuals carrying the -308G allele, but not the waist-to-hip ratio. No
      apparent influence of the -308A polymorphism on other metabolic indicators
      (insulin and leptin levels) was found. We could not detect any association
      between the substitution at position -238 polymorphism of the TNF-alpha gene and
      obesity anthropometrical phenotypes in this Spanish population, despite some
      differences in plasma leptin. These results support the hypothesis that the G/A 
      308 polymorphism of the TNF-alpha gene is associated with a higher BMI as well as
      hip ad waist circumferences, particularly on female bearers, while no influence
      on such measurements was found for the G/A -238 TNF-alpha gene polymorphism, but
      only an effect on leptinaemia.

PMID- 15163122
TI  - Investigating symptoms: use of questionnaires in gastroenterology.

PMID- 15163121
TI  - Drug-induced severe hypoglycaemia in Type 2 diabetic patients aged 80 years or
      older.
AB  - Our knowledge about the risk of hypoglycaemia associated with diabetes treatment
      is derived from studies that often exclude elderly people. Aim of this study was
      to determine the incidence and risk factors for developing severe hypoglycaemia
      among persons aged 80 yr or older, with Type 2 diabetes mellitus (T2DM). During a
      2-yr period, all episodes of severe hypoglycaemia occurred in T2DM patients aged
      80 yr or older were identified. Hypoglycaemia was defined as a symptomatic event
      requiring treatment with i.v. glucose and confirmed by a blood glucose
      determination of less than 50 mg/dl. A detailed history and blood laboratory
      profile were obtained for each patient. During the period of the survey a total
      of 124 diabetic subjects aged 80 yr or older were hospitalised and severe
      hypoglycaemia was reported in 31 patients (25%). This group of patients had a
      marked comorbidity and was found to have HbA1c values of 5.1% indicating that
      their diabetes was well controlled. Of these hypoglycaemic episodes, 23 (74%)
      occurred in patients taking glibenclamide. Diabetes therapy was prescribed by
      general practitioners in 24 of these patients. Seventeen subjects concomitantly
      received drugs that potentiated hypoglycaemia. Only 10 patients performed regular
      blood glucose self-monitoring. In conclusion, severe hypoglycaemia is a serious
      and not uncommon problem among elderly patients with T2DM; it is more frequent in
      patients undergoing aggressive diabetes management and in users of a long-acting
      sulphonylurea (eg, glibenclamide). A normal HbA1c level in this age group appears
      to be a powerful indicator of the risk of severe hypoglycaemia and should alert
      clinicians to change therapy. Finally, each patient's risk for hypoglycaemia
      should be considered and therapy should be individualised accordingly; in our
      opinion, a great number of episodes of serious hypoglycaemia may be prevented by
      teaching the principles of blood glucose monitoring and involving general
      practitioners in outpatient management of diabetes mellitus in the elderly.

PMID- 15163123
TI  - Intestinal manometry: value and limitations.

PMID- 15163124
TI  - Ultrasonography in the assessment of gastric and gallbladder motor function.

PMID- 15163125
TI  - Gastric emptying evaluation by 13C-octanoic acid breath test.

PMID- 15163126
TI  - Glycaemic control and gastric emptying.

PMID- 15163127
TI  - Measurement of gastrointestinal sensitivity.

PMID- 15163129
TI  - Helicobacter pylori infection and diabetic complications.

PMID- 15163128
TI  - Type 1 (insulin-dependent) diabetes mellitus and gastric emptying: role of blood
      glucose concentration and dopamine D2 receptors.

PMID- 15163130
TI  - Oesophageal motor disorders in Type 1 diabetic patients.

PMID- 15163131
TI  - Effects of hyperinsulinaemia on erythromycin-induced gallbladder and gastric
      motility in normal subjects.

PMID- 15163132
TI  - How to develop the basic and applied science of health promotion.

PMID- 15163133
TI  - Effects of a self-determination theory-based mail-mediated intervention on
      adults' exercise behavior.
AB  - PURPOSE: To examine the effect of a mail-mediated intervention, based on self
      determination theory, on adults'exercise behavior. METHODS: The study was a
      randomized control trial conducted over a 2-month period. Of the initial 185
      volunteer participants, 126 (68.1%) completed questionnaires at baseline, 1
      month, and 2 months. Participants in intervention-only and intervention-plus
      booster groups received a mail-delivered packet containing strategies designed to
      promote perceptions of autonomy, competence, and relatedness regarding exercise.
      Those in a control group received an American Heart Association physical-activity
      facts packet. After 1 month, those in the intervention-plus-booster group
      received a booster postcard, reiterating the main points of the initial
      intervention packet. Exercise behavior was the primary outcome variable.
      Perceptions of autonomy, competence, and relatedness were evaluated as mediating
      variables. RESULTS: Separate 3 (group) x 3 (time) repeated measures analyses of
      variance conducted for men and women revealed that for women, all three groups
      significantly increased exercise levels over the 2-month period. No significant
      interactions were found regarding the influence of the intervention on the
      mediating variables. A process evaluation indicated a lack of compliance
      regarding completing intervention-packet worksheets. DISCUSSION: Findings
      suggested that more intensive interventions and greater fidelity of treatment may
      be needed to evidence change in exercise behavior.

PMID- 15163134
TI  - The relationships between delivery agents' physical activity level and the
      likelihood of implementing a physical activity program.
AB  - PURPOSE: To determine the relationships between delivery agents'physical activity
      characteristics and subsequent adoption of a physical activity promotion program
      for community implementation. METHODS: Agents responsible for county health
      promotion in Kansas (n = 91; 94.5% women; mean age = 43.0 +/- 11) completed
      interviews that assessed physical activity self-efficacy, value, and
      participation. Subsequent implementation of a physical activity program was
      monitored. The response rate was 100%. RESULTS: Fifty-five percent of the agents
      met Centers for Disease Control and Prevention (CDC) recommendations for physical
      activity, 35% were active but did not meet CDC recommendations, and 10% were
      inactive. On the basis of logistic regression analysis (Wald statistic = 7.63; p
      < .05), agents who met recommendations were more likely to adopt the program for
      their county (69%) than were agents who were less active (41%) and inactive
      (11%). DISCUSSION: The data suggest that increasing the proportion of delivery
      agents who meet the CDC recommendations for physical activity could be related
      with a higher proportion of communities implementing physical activity programs.

PMID- 15163135
TI  - The relationships among constructs in the health belief model and the
      transtheoretical model among African-American college women for physical
      activity.
AB  - PURPOSE: Health Belief Model (HBM) and Transtheoretical Model concepts were used
      to investigate possible differences in perceptions of physical activity among
      African-American college women categorized by their stage of physical activity
      behavior METHODS: A survey was administered to 233 participants to assess their
      stage of physical activity behavior and HBM perceptions. Analysis of variance was
      used to investigate possible differences among HBM constructs for each behavior
      stage. RESULTS: Perceived barriers were significantly higher (p < .05), and
      perceived severity, cues to action, and self-efficacy were significantly lower in
      the inactive group than in the active group. For example, perceived barriers were
      significantly higher in the inactive (mean = 2.3) stage than in the preparation
      (mean = 2.1), action (mean = 1.9), and maintenance (mean = 1.7) stages of
      physical activity behavior. DISCUSSION: The results suggest that many perceptions
      of physical activity differ significantly among stages of behavior in this sample
      of African-American college women. A limitation was that some scales were
      modified specifically for this population and were not validated.

PMID- 15163136
TI  - Prevalence and patterns of environmental tobacco smoke exposures among California
      teachers.
AB  - PURPOSE: This study describes the prevalence and patterns of environmental
      tobacco smoke (ETS) exposure in a large, well-defined cohort of professional,
      female school employees in California. DESIGN: This is a cross-sectional study
      based on survey responses from members of the California Teachers Study (CTS)
      cohort. SUBJECTS: The analyses focused on lifetime nonsmokers (N = 61,899) in the
      CTS cohort who responded to detailed questions on lifetime ETS exposures in the
      home, workplace, and other social settings. MEASURES: Demographic
      characteristics, smoking status, and ETS exposure were based on self-reported
      data from two mailed surveys. Prevalence estimates within the cohort were
      compared with those from the California Behavioral Risk Factor Survey and the
      California Adult Tobacco Survey. RESULTS: ETS exposures were highest for never
      smokers born in the 1930s (78% in the home, 66% in the workplace, and 48% in
      other social settings) and steadily declined among participants born in later
      years. ETS exposure from spousal smoking peaked during the 1950s (37%). In the
      1980s, the workplace (28%) replaced the household (19%) as the primary exposure
      setting. CONCLUSIONS: Consideration of these patterns in the prevalence of ETS
      exposures is important in the interpretation and design of tobacco-related health
      studies.

PMID- 15163137
TI  - Does a health plan effort to increase smokers' awareness of cessation medication
      coverage increase utilization and cessation?
AB  - PURPOSE: To test whether a mailing describing new coverage for smoking cessation
      medications increases benefit knowledge, utilization, and quitting. METHODS: This
      randomized controlled trial assigned participants to benefit communication via
      (1) standard contract changes or (2) enhanced communication with direct-to-member
      postcards. A sample of 1930 self-identified smokers from two Minnesota health
      plans took surveys before and 1 year after the benefit's introduction. The follow
      up response rate was 80%. A multilevel logistic estimator tested for differences
      in benefit knowledge and smoking behavior from baseline. RESULTS: More enhanced
      than standard communication respondents knew about the benefit (39.0% vs. 22.2%,
      p < .0001) at follow-up. Groups did not differ on bupropion utilization (24.6%
      vs. 23.1%, p = .92); nicotine replacement therapy utilization (26.9% vs. 25.9%, p
      = .26), or cessation (12.8% vs. 15.6%, p = .32). CONCLUSION: Although limited by
      the low intervention intensity and potential social desirability bias,
      information about new coverage alone does not appear to increase quitting
      behaviors.

PMID- 15163138
TI  - Factors underlying variation in receipt of physician advice on diet and exercise:
      applications of the behavioral model of health care utilization.
AB  - PURPOSE: To identify factors associated with receipt of physician advice on diet
      and exercise, including patient sociodemographic characteristics, health-related
      needs, and health care access, using Andersen's model of health care utilization.
      DESIGN: A cross-sectional analysis was performed using data from the 2000
      National Health Interview Survey (NHIS). SETTING: NHIS data were collected
      through personal household interviews by Census interviewers. The overall
      response rate for the 2000 NHIS adult sample was 82.6%. SUBJECTS: Subjects were a
      representative sample of the American civilian, noninstitutionalized population
      aged 18 and older. After eliminating missing data and respondents who reported
      they did not see a doctor in the past 12 months, sample sizes for physician
      advice on diet and exercise were n = 26,255 and n = 26,158, respectively.
      MEASURES: Using the 2000 NHIS, the prevalence of receipt of physician advice on
      diet and exercise was assessed. Multiple logistic regression analyses were
      performed to examine the associations between receipt of physician advice on diet
      and exercise and potential predictors, adjusting for all covariates. RESULTS: By
      self-report, 21.3% and 24.5% of respondents received physician advice on diet and
      exercise, respectively. Being middle-aged (adjusted odds ratio [AOR] = 1.14, 95%
      confidence interval [CI], 1.0-1.29 for diet; AOR = 1.55, 95% CI = 1.33-1.79 for
      exercise) and having a baccalaureate degree or higher (AOR = 1.78, 95% CI = 1.52
      2.08 for diet; AOR = 1.75, 95% CI = 1.47-2.07) were associated with a higher
      likelihood of receiving physician advice on diet and exercise. African-Americans
      (AOR = .78, 95% CI = .67-.92) and foreign-born immigrants (AOR = .57, 95% CI =
      .38-.86) were less likely to receive physician advice on exercise. The prevalence
      of physician advice was higher for persons who chose hospital outpatient
      departments as a usual source for care (AOR = 2.36, 95% CI = 1.66-3.36 for diet;
      AOR = 2.39, 95% CI = 1.68-3.4 for exercise) than for adults with other types of
      usual care sites. Poorer self-rated health status (AOR = 5.2, 95% CI = 4.12-6.57
      for diet; AOR = 2.63, 95% CI = 2.04-3.38 for exercise) and obesity (AOR = 2.32,
      95% CI = 2.02-2.66 for diet; AOR = 3.01, 95% CI = 2.46-3.69 for exercise) was
      positively associated with the likelihood of receiving physician advice on diet
      and exercise. CONCLUSIONS: Effective strategies to increase receipt of physician
      advice should include efforts to improve access to regular source of care and
      patient-physician communication. Sociodemographic factors remain independent and
      important predictors of who obtains such advice.

PMID- 15163140
TI  - Proportion of trips made by walking: estimating a state-level baseline for
      Healthy People 2010 Objective 22-14.
AB  - PURPOSE: The purpose of this study was to investigate the proportion of short
      trips made by walking among Michigan adults and barriers to walking for
      transportation. METHODS: Four questions on walking for transportation were asked
      of 3808 respondents to the Michigan Behavioral Risk Factor Surveillance System
      (BRFSS) between January and December 2001. RESULTS: Three quarters (74.3%) of
      Michigan adults were estimated to have made at least one short trip (.25-1 mile)
      in the previous week; however, only 36.2% of them walked even one of these trips.
      The mean proportion of short trips walked was 21.4%; less than 10% of all
      respondents walked five or more trips per week. DISCUSSION: Our results provide a
      Michigan-specific baseline for Healthy People 2010 Objective 22-14 (i.e.,
      increase the proportion of trips made by walking) and suggest the potential for
      these questions to be used to monitor active transportation via the BRFSS.

PMID- 15163139
TI  - Unsafe to play? Neighborhood disorder and lack of safety predict reduced physical
      activity among urban children and adolescents.
AB  - PURPOSE: Lack of physical activity is associated with increased risk of
      overweight and cardiovascular disease, conditions associated with lower
      socioeconomic status (SES). Associations between activity levels of urban youth
      and limited access to safe recreation areas in their neighborhoods of residence
      were investigated. DESIGN: Analyses of data from the Project on Human Development
      in Chicago Neighborhoods, a multilevel longitudinal study of families and
      communities, are reported. SETTING: Chicago, Illinois. SUBJECTS: Individual-level
      data were obtained from 1378 youth 11 to 16 years old and caregivers living in 80
      neighborhood clusters. Neighborhood-level data were collected from 8782 community
      residents and videotapes of 15,141 block faces. MEASURES: Parental estimates of
      hours youth spent in recreational programming were used to estimate physical
      activity. A scale of residents' assessment of neighborhood safety for children's
      play was created; disorder measures came from videotaped observations. RESULTS:
      Physical activity averaged 2.7 hours/week (SD = 5.0), varying significantly
      across neighborhoods. Using hierarchical linear regression, SES, age, and male
      gender, but not body mass index, were independently associated with physical
      activity. Lower neighborhood safety and social disorder were significantly
      associated with less activity, controlling for demographics. CONCLUSIONS: One
      mechanism for reduced physical activity among youth may be the influence of
      unsafe neighborhoods. Neighborhood interventions to increase safety and reduce
      disorder may be efficacious in increasing physical activity, thereby reducing
      risk of overweight and cardiovascular disease.

PMID- 15163141
TI  - Serving older adults with health promotion.

PMID- 15163142
TI  - Serving higher education communities with health promotion.

PMID- 15163143
TI  - Serving racial and ethnic populations with health promotion.

PMID- 15163144
TI  - A simplified technique for the restoration of severely mutilated primary anterior
      teeth.
AB  - The restoration of severely carious primary anterior teeth is a challenge to the
      pediatric dentist. The introduction of new materials and technologies makes re
      evaluation of existing treatment philosophies necessary. A technique involving
      the placement of an omega shaped stainless steel wire extension into the entrance
      of the root canal prior to restoring the crown with a compomer material is
      described. 96 restorations were placed in 25 children. After 18 months 81.2% of
      the 96 restorations, which were available for evaluation, 60 (79.9%) were intact.
      The technique for restoring primary anterior teeth was simple, quick and
      effective.

PMID- 15163145
TI  - Dentistry for babies: why do parents seek dental care?
AB  - This study investigated what are the main reasons that led parents to enroll
      children in a clinic for infants. This was studied by consulting 1368 records
      during the period from July 1996 to August 2001. The predominant reason for
      enrolling was orientation/prevention followed by "other" and treatment. This
      study demonstrated that a program for children from the first year of life
      encourages parents to have a new vision of dentistry.

PMID- 15163146
TI  - Delayed eruption of maxillary permanent central incisors as a consequence of
      mesiodens: a surgical re-treatment approach.
AB  - The presence of mesiodens can cause some clinical problems. This paper reports a
      case of delayed eruption of permanent central incisors in a nine-year-old male as
      a consequence of a mesiodens and three surgical approaches prior to the eruption
      of incisors, which occurred after the third surgery when the crown was exposed
      and submitted to a gentle luxation.

PMID- 15163147
TI  - Resin bonded metal plate as a splint for fractured restored teeth: a case report.
AB  - This article presents a case with traumatic tooth fracture that was treated by
      direct pulp capping followed by fragment restoration. The fixed parts were
      reinforced by resin bonded metal plates.

PMID- 15163148
TI  - Biological factors in dental caries: role of remineralization and fluoride in the
      dynamic process of demineralization and remineralization (part 3).
AB  - Dental caries is a complex disease process that afflicts a large proportion of
      the world, regardless of gender, age and ethnicity, although it does tend to
      affect more with a low socioeconomic status to a greater extent. Remineralization
      may be enhanced by providing low levels of calcium and phosphate, in conjunction
      with minimal amounts of fluoride. It is truly remarkable the difference that a
      very small amount of fluoride (<1 ppm) has upon demineralization and
      remineralization. This is because fluoride acts as a catalyst and influences
      reaction rates with dissolution and transformation of various calcium phosphate
      mineral phases within tooth structure and resident within plaque adjacent to
      tooth surfaces. The incorporation of minimal amounts of fluoride into HAP yields
      FHAP that resists demineralization to similar level as FAP. New and emerging
      methods have been and are in the process of being developed. These hold great
      promise for preventing and reversing caries, especially in the one-fifth of the
      population that accounts for two-thirds of the caries experience. Still, the
      mainstay in caries prevention and remineralization is frequent exposure to low
      levels of fluoride. This may be accomplished with fluoridated toothpastes,
      supplemented with fluoride mouthrinses, CPP-ACP containing chewing gum and
      application of fluoride varnishes. The role of systemic fluorides appears to be
      limited and primarily has a topical effect.

PMID- 15163149
TI  - Panoramic radiographic findings of the mandibular foramen from deciduous to early
      permanent dentition.
AB  - The purpose of this study was to investigate the position of the mandibular
      foramen from deciduous (Hellman's stage IIA) to early permanent dentition
      (Hellman's stage IVA). Panoramic radiographs of 311 Taiwanese children were used.
      The results revealed that the distances between the mandibular foramen and ramus
      anterior plane were greater than those between the mandibular foramen and ramus
      posterior plane through all stages. The mean difference between them was the
      smallest (0.25 mm) in stage IIA and the greatest (1.18 mm) in stage IIIC. The
      distance from the mandibular foramen to the alveolar crest plane showed a little
      change from stage IIA (3.99 mm) to IVA (5.26 mm). The gonial angle had a negative
      correlation with the distances between the mandibular foramen and each mandibular
      border. Evaluation of the mandibular foramen from the oral aspect can be
      influenced by the degree of mouth opening.

PMID- 15163150
TI  - Alveolar bone height in infraoccluded primary teeth.
AB  - The purpose of this research is to describe the distance from the cemento enamel
      junction (CEJ) to the alveolar bone crest (ABC) of infra occluded primary molars
      and the adjacent and opposing teeth. Bitewing radiographs from 29 children (mean
      age 98.8 months; SD 21.2), who had infra occluded molars, were scanned and
      measured. The results of these measurements found that the means of the CEJ-ABC
      distances of the mesial and distal aspects of the infra occluded teeth were 0.78
      mm (SD 0.3) and 0.94 mm (SD 0.32) respectively. Pearson correlation coefficient
      analysis revealed no significant correlation between the different measurements,
      except when comparing the measurements in the infra occluded tooth and those of
      the opposing tooth. It was concluded that the CEJ-ABC values for infra occluded
      primary molars are shorter than normal values. The CEJ-ABC distances of the
      opposing and adjacent teeth to the infra occluded tooth are within normal limits.

PMID- 15163151
TI  - Effects of timing and number of palate repair on maxillary growth in complete
      unilateral cleft lip and palate patients.
AB  - This cross-sectional study was conducted on 40 subjects to investigate the
      effects of timings and number of palate surgeries on maxillary growth in complete
      unilateral cleft lip and palate patients. The number of surgeries performed for
      palate repair was not an important growth inhibiting factor of maxilla, rather
      the age at which the initial palate surgery was performed for palate repair was
      an important factor in influencing maxillary growth.

PMID- 15163152
TI  - Evaluation of TMJ by conventional transcranial radiography and indirect digitized
      images to determine condylar position in primary dentition.
AB  - The aim of this study was to evaluate temporomandibular joint radiographs of
      children in primary dentition, obtained by conventional transcranial radiography,
      indirect digitization, digitized images using 3D and brightness/contrast tools.
      Condyle position was also determined measuring anterior, superior and posterior
      joint space. The X-Ray machine GE-1000 and the head positioner Accurad 200 were
      used. Radiographs were digitized using a scanner with transparency and registered
      in Adobe Photoshop 5.0. Images were evaluated by four examiners as follows: 0-
      unacceptably quality; 1--poorly diagnostic quality; 2--optimal visualization
      quality. Articular space was measured using a digital caliper. A significant
      difference (Sign Test) was found between conventional radiography and the
      remaining modalities (Conventional/Unenhanced p<0.001; Conventional/3D p<0.001;
      Conventional/Brightness and Contrast p=0.017). The mean distance of anterior,
      superior and posterior regions was 2.2(0.5), 3.5(0.9) and 3.9(1.2) mm,
      respectively. Conventional and brightness/contrast digitized radiographs showed
      higher diagnostic quality. The posterior joint space was larger than the anterior
      one, demonstrating anterior condylar position.

PMID- 15163153
TI  - Salivary characteristics of children and its relation to oral microorganism and
      lip mucosa dryness.
AB  - The aim of this paper was to present baseline data on various saliva properties
      among a group of Saudi children aged 5 to 11 years and to study the relationship
      of these properties to some oral micro-organisms as well as to lip and oral
      mucosa dryness. The results showed a mean of resting and stimulated flow rate of
      0.54 +/- 0.40 and 1.23 +/- 0.59 respectively and mean pH value of 7.27 +/- 0.38
      and 7.5 +/- .035 respectively. Fluoride concentration was estimated to be 0.151
      +/- 0.07 and 0.145 +/- 0.06 in resting and stimulated saliva respectively.
      Children with dry lip represented 33.9% of the sample population, whereas, those
      with dry mucosa represented only 0.8%. No significant sex difference was evident
      in all parameters. 59.1% of children showed medium buffering capacity in the
      resting saliva, whereas, the majority of children (73.7%) showed high stimulated
      buffering capacity. Children showed generally high Lactobacillus counts (Lb) in
      the resting and stimulated saliva (57.9% and 60.5% of children). The presence of
      yeast also in resting and stimulated saliva seemed high in general (40% and 53%
      of children had high count). However, Streptococcus mutans (S. mutans) counts
      showed no discriminating trend in both types of saliva. The data showed no
      significant association between flow rate and Lb counts in both resting and
      stimulated saliva although there was a trend toward higher counts associated with
      low flow rate. The same trend was observed in resting saliva although not
      significant. Similarly, low resting buffering capacity was associated with high
      counts of Lb among a high proportion of children (68.6% of children) although not
      significant. A significant reverse relation was evident between S. mutans counts
      and stimulated flow rate (p=0.049). The majority of children with normal level of
      saliva pH showed no yeast colonization (62.1%). The association was significant
      (p=.024). Similarly, the same association was observed in the medium and high
      buffering group (66.2%) (p=.040). It was concluded that salivary Lb count seems
      to be primarily affected by some local factors other than salivary properties,
      such as diet. Significant inverse relationship was found between S. mutans and
      stimulated salivary flow. Children in general showed high percentage of yeast
      reflecting the affect of poor diet among the studied population group. Buffering
      capacity and pH had an important role in yeast colonization.

PMID- 15163154
TI  - Comparison of three different preparation methods in the improvement of sealant
      retention.
AB  - The purpose of this in vitro study was to evaluate the effect of three invasive
      fissure preparation methods in the retention of sealant on the surfaces of
      permanent molars. One hundred and eight extracted caries-free human molars were
      used in this study, which were divided into 3 groups according to the fissure
      preparation: laser, air abrasion and bur. In addition, each of these three groups
      was further divided into 2 additional groups to isolate those in which a bonding
      agent would be used from those in which a bonding agent would not be used. After
      the accomplishment of the different treatments samples from all the 6
      experimental groups were submitted to two different bond strength tests: (i)
      shear bond strength test and (ii) tensile bond strength test. Bond strengths were
      determined by the dividing fracture load and a statistical test ANOVA was used to
      evaluate significant differences. The results showed that laser improved the
      sealant retention when compared with air abrasion preparation when the bonding
      agent was used. The use of bonding agent increased the sealant retention in all
      methods except for tensile bond strength when air abrasion was used as the
      preparation method

PMID- 15163155
TI  - Titanium penetration in human enamel after TiF4 application.
AB  - The TiF4 application produces a titanium coating on enamel surface, reducing
      solubility in presence of cariogenic challenge. However, it is not established if
      this titanium also penetrates inside the enamel. The aim of this study was to
      evaluate in vitro the presence of this superficial coat and titanium penetration
      into human sound and decayed enamel after TiF4 application. Twenty-four unerupted
      third molars were mesiodistally cut and divided into two groups (GA--sound and GB
      -artificial decayed). After a 4% TiF4 application, each sample was fractured
      longitudinally (occlusal-cervical). Through microprobe analysis with energy
      dispersive spectrometer (EDS), titanium penetration could be observed inside the
      enamel. The McNemar test (p=0.267) showed that there was no difference between
      the groups analyzed regarding to titanium penetration, although in group A the
      titanium penetrated more deeply (Wilcoxon test, p=0.047). It could be concluded
      that there was no difference between the groups regarding the titanium
      penetration, but titanium penetrated more deeply into sound enamel compared to
      artificially decayed enamel.

PMID- 15163156
TI  - Six-year clinical evaluation of polyacid-modified composite resin used as fissure
      sealant.
AB  - The aim of this study was to evaluate retention and efficacy of polyacid-modified
      composite resin used as fissure sealant (Variglass V.L.C.) after six years. Three
      hundred and seventy permanent first molars were sealed. After six years, 42.0% of
      the original group was re-examined and the sealant was found to be totally
      present in 3.4%, partially present in 16.2% and absent in 70.4% of the previously
      sealed occlusal surfaces. During the 6 years period, 9.5% of the sealed surfaces
      became carious, 25.0% were filled and 65.5% remained sound. Although the
      retention rate of the material has been very low, it appears to have prevented
      dental caries in 2/3 of the teeth evaluated after six years of placement.

PMID- 15163157
TI  - Efficacy of a self-etching dentin primer composed of TEGMA and phenyl-P.
AB  - The purpose of the present study was to evaluate the efficacy of an experimental
      self-etching dentin primer composed of TEGMA and phenyl-P using primary and young
      permanent teeth. The efficacy of the self-etching dentin primer was evaluated by
      measuring the wall-to-wall polymerization contraction gap width and the shear
      bond strength to the flat dentin surface. The contraction gap formation was
      prevented completely in the specimens primed with the 35 vol% TEGMA and 20%
      phenyl-P for 30 sec.

PMID- 15163158
TI  - Van der Woude syndrome: a report of two cases.
AB  - Van der Woude syndrome is a rare autosomal dominant condition with high
      penetrance and variable expression. It consists of a cleft lip and/or palate pits
      on the vermilion of the lower lip, and hypodontia. Two cases of congenital lip
      pits with cleft lip and alveolus and an isolated cleft palate are described to
      illustrate the variable presentation of the clinical features and the importance
      of early recognition of Van der Woude syndrome because of the genetic
      implications.

PMID- 15163159
TI  - Dental erosion: a complication of pervasive developmental disorder.
AB  - A young teenage male presenting for a routine check-up reported no health
      problems. Initial clinical examination revealed some enamel loss on the palatal
      surfaces of the maxillary incisors. Erosion lesions were suspected. Similar
      lesions, however, were not found throughout the mixed dentition and radiographic
      findings were inconclusive. To confirm the diagnosis of these lesions and, more
      importantly, to disclose the etiology, a thorough and detailed clinical
      examination of these lesions was conducted. Study models were made, mounted in
      centric occluding position, and closely screened. In addition, the health history
      was revisited, by interviewing the patient and his legal guardian. The
      information gathered led to the conclusion that the lesions in question were
      erosion lesions with concomitant wear facets that resulted from attrition of the
      softened enamel surface. An ample light on the possible etiological factors was
      shed, which assisted in the planning phase for the course of management. It is
      not uncommon that dental health care providers encounter in daily practice cases
      of early erosion lesions similar to those reported here. In most of these
      instances, minor changes in tooth morphology that represent a slight departure
      from the norm could be overlooked and often ignored. If such lesions go
      undetected, the underlying causes may escape diagnosis. However, if action is
      taken to pursue investigation of the causative factor, the result could assist in
      understanding the overall complexity of the health condition of the patient. This
      would enable planning the proper course of management for the total well being of
      the patient.

PMID- 15163160
TI  - Long-term sequelae after cancer therapy--a necessary consequence of success?

PMID- 15163161
TI  - Long-term sequelae after cancer therapy--survivorship after treatment for
      testicular cancer.
AB  - This paper is based on a lecture given during the Oncological Forum, Oslo, in
      November 2002. Long-term morbidity in cancer survivors is exemplified by results
      of clinical research in testicular cancer survivors (TCSs). The most serious
      complication is the development of second, non-germ cell malignancies (relative
      risk [RR]: 1.4-1.6). After infradiaphragmatic radiotherapy, most solid
      malignancies are diagnosed within or near the target volume. Combined chemo
      radiotherapy increases this risk. Chemotherapy-induced leukaemia is usually
      reported after 4-7 years. After 3 or 4 cycles of cisplatin-based chemotherapy, 15
      20% of TCSs suffer from peripheral sensory neuropathy, Raynaud-like phenomena
      and/or ototoxicity. Hypogonadism is observed in 16%. The risk of cardiac
      complications is increased by hypercholestorolaemia and abnormal body mass.
      Pelvic radiotherapy and cisplatin-based chemotherapy are followed by transient
      oligo/azospermia with recovery after 6-12 months. The risk of surgery-related
      'dry ejaculation' is significantly reduced after unilateral and nerve-sparing
      retroperitoneal lymph node dissection, but infertility remains a long-term
      problem in 10-15% of survivors. Most TCSs describe their quality of life as
      comparable with that of the age-matched male general population. Not all long
      term complications are avoidable after curative treatment of cancer. Knowledge of
      post-treatment long-term morbidity is essential for early recognition and
      treatment of late complications, and enables adequate counselling of new cancer
      patients.

PMID- 15163162
TI  - Angiotensin converting enzyme inhibitors for cancer treatment?
AB  - Angiotensin converting enzyme inhibitors (ACEi) prescribed for cardiovascular and
      renal disease since 1980 are widely atoxic and several experimental studies and
      one epidemiological study have demonstrated an effect of ACEi on cancer. ACEi has
      the effect of modifying gene expression; inhibiting proliferation and invasion of
      cancer cells; reducing endothelial cell migration and angiogenesis in vitro,
      whereas tumour growth and metastasis were inhibited in vivo. Several mechanisms
      of action are possible but inhibition of matrix metalloprotease activity, reduced
      expression of vascular endothelial growth factor and interference with the renin
      angiotensin system were demonstrated by the experimental studies. In this paper
      we review the laboratory investigations and epidemiological studies on the anti
      cancer actions of ACEi and present a summary of the evidence regarding the
      potential use of ACEi in cancer treatment.

PMID- 15163164
TI  - Anxiety and depressive symptoms measured by the Hospital Anxiety and Depression
      Scale as predictors of time to recurrence in localized cutaneous melanoma.
AB  - The purpose of this study was to investigate anxiety and depression as predictors
      for recurrence-free survival in cutaneous melanoma, when corrected for known
      prognostic factors. The association between known prognostic factors and anxiety
      and depression were also studied. Consecutive patients (n = 437) completed the
      Hospital Anxiety and Depression Scale (HAD) approximately three months after
      diagnosis of melanoma. Neither anxiety, nor depression turned out to be
      prognostic factors for time to recurrence. A higher proportion of young patients,
      women, patients without ulcerated tumours, patients with tumours with low mitotic
      index and Clark's level II tumours scored > or = 8 (possible clinical levels of
      anxiety) on the anxiety scale. Furthermore, on the depression scale, a higher
      proportion of young patients scored > or = 8 (possible clinical level of
      depression). Using the HAD scale, a well-validated instrument for assessing
      anxiety and depression in patients with somatic diseases, our data did not show
      any associations between anxiety or depression and outcome in terms of recurrence
      in patients with localized disease.

PMID- 15163163
TI  - Normative data for functional assessment of cancer therapy--general scale and its
      use for the interpretation of quality of life scores in cancer survivors.
AB  - The aims of this study were to derive population-based reference values for the
      Functional Assessment of Cancer Therapy Scale-General (FACT-G) and to investigate
      the impact of sociodemographic variables (e.g. age, sex, health status) on these
      quality of life (QOL) scores, and to compare the normative QOL scores with those
      of various groups of cancer survivors. A random sample of 2 000 members of the
      Austrian public were sent questionnaires containing the FACT-G and questions
      relating to demographic data and health status. A total of 968 questionnaires
      were returned giving an overall response rate of 50.6% (females 48.3%, age 49.3
      +/- 16.8). Subjects with higher education reported higher QOL values; divorced
      and widowed persons had significantly lower QOL scores. Higher age was also
      associated with lower QOL scores. After bone marrow transplantation, patients
      generally showed lower QOL scores than the age- and sex-matched population-based
      sample, whilst in breast cancer survivors there was reduced QOL regarding social
      well-being. Survivors of Hodgkin's disease were found to have higher functional
      and social well-being scores than those of the general population sample.
      Sociodemographic variables should always be taken into consideration when
      interpreting QOL scores. Furthermore, unless patient data are compared with
      normative values, phenomena such as adaptation and response shift might be missed
      or misinterpreted.

PMID- 15163165
TI  - Concomitant vinorelbine and radiation in head and neck squamous cell carcinoma in
      vitro.
AB  - Concomitant chemoradiotherapy has been used for locally advanced head and neck
      squamous cell carcinoma (HNSCC) particularily with cisplatin, 5-FU, methotrexate,
      bleomycin and taxanes. Vinorelbine is a semisynthetic vinca alcaloid, which
      causes a block in the G2/M phase of the cell cycle. HNSCC cell lines have
      previously been reported to be sensitive to vinorelbine in nanomolar
      concentrations. In the current study the effect of vinorelbine as a
      radiosensitizer in vitro was studied and eight recently established head and neck
      SCC cell lines of the UT-SCC-series were tested. Vinorelbine concentrations of
      0.4-1.6 nM were used, corresponding to the IC70, IC50 and IC30 values of each
      cell line, resulting in 30%, 50% and 70% inhibition in clonogenic survival. The
      desired concentrations of vinorelbine were added to the medium and the cells were
      plated in 96-well culture plates in this solution. The plated cells were
      irradiated 24 h later with 4MeV photons generated by a linear accelerator and
      incubated at 37 degrees C with 5% CO2 for 4 weeks. Thereafter, the number of
      wells containing coherent, living colonies, consisting of 32 cells or more, was
      counted. The plating efficiency was calculated and the fraction survival data
      were fitted to the linear quadratic model [F = exp[-(alphaD + betaD2)]]. An
      additive effect of combining vinorelbine and irradiation could be demonstrated.
      The dose-dependent decrease in survival was seen at vinorelbine doses of 0.4-1.6
      nM in all cell lines tested.

PMID- 15163166
TI  - Diagnosis and prognosis of breast and ovarian cancer--a population-based study of
      234 women.
AB  - The diagnosis and prognosis for 135 women with breast cancer and 99 women with
      ovarian cancer in a well-defined geographical area, and a follow-up of 7-15 years
      are described, based on patients' records. Diagnosis was initiated in primary
      care for 53% of women with breast cancer, and for 57% of women with ovarian
      cancer. Median patient delay was 1 week for breast cancer, and 3.5 weeks for
      ovarian cancer patients, and median provider delay was 3 weeks for both groups.
      Crude, relative, and corrected 5-year survival was 73%, 91%, and 82% in breast
      cancer, and 40%, 49%, and 43% in ovarian cancer. Cox multiple regression analyses
      showed that stage IIIA and IV, and young age were associated with impaired
      disease-related survival in breast cancer. In patients with ovarian cancer,
      stages III and IV at diagnosis, old age, and systemic symptoms dominating at
      presentation were predictive of reduced disease-related survival while a family
      history of cancer was predictive of increased survival.

PMID- 15163167
TI  - Enlarged axillary nodes and position of the arms in axillary irradiation--a
      computed tomography and magnetic resonance imaging evaluation.
AB  - The purpose of this study was to evaluate the axillary node displacement away
      from chest wall and their anatomical location in relation to the humeral head,
      according to the position of the arms, when the axilla is the site of enlarged
      nodes. In 13 patients with enlarged axillary nodes, the anatomical span of the
      nodes according to two arms positions, akimbo (A) and up over the head (U), was
      prospectively evaluated using computed tomography (CT) and magnetic resonance
      imaging (MRI). The nodes were classified into two groups, i.e. the lower and
      upper groups. The mean distances of the lower node group from the chest wall when
      the patients were in A, and U positions were 3 cm and 6.4 cm, respectively (p =
      0.002). The upper group nodes showed a smaller difference in the distance from
      the chest wall: in A position, mean 2.1 cm; in U position 2.8 cm (p = 0.03). In U
      position, there was always a node of the lower group that was displaced in front
      of the humeral head. This study demonstrates the displacement of enlarged
      axillary nodes according to the position of the arms. In patients with axillary
      node involvement, CT planning should be considered when they have their arms held
      up over their heads.

PMID- 15163168
TI  - Oral capecitabine in anthracycline- and taxane-pretreated advanced/metastatic
      breast cancer.
AB  - An open-label, non-randomized, compassionate-use study was carried out to
      investigate the effects of oral capecitabine at a dose of 1 250 mg/m2 twice daily
      on days 1 to 14 every 21 days in anthracycline- and taxane-pretreated
      advanced/metastatic breast cancer patients. Forty-eight patients were enrolled
      from April 2000 to December 2001. Twenty-four patients (50%) had metastases to
      the liver, 18 to bone, 13 to lung, 10 to regional lymph nodes, 8 to pleura, 7 to
      the thoracic wall, 5 to skin, 3 to the mediastinum, 1 to breast and 1 had
      metastasis to the abdomen. Thirty-three patients (69%) had metastases to more
      than one site. Median age of the patients was 55 years (range 35-74). Three
      patients had an ECOG performance status (PS) of 0, 32 PS 1 and 13 PS 2,
      respectively. Fourteen patients (29%; 95% CI 16 to 42%) obtained a partial
      response (PR) while 16 (33%) had stable disease (SD) as the best response, of
      whom 6 had stabilization for more than 24 weeks. This gives a clinical benefit
      (PR + SD > 24 weeks) of 42% (95% CI 28 to 56). Dose reduction was necessary in
      29% of the patients. Median dose reduction was 25%. Grades 2 and 3 hand-foot
      syndrome (PPE) was observed in 17 patients (36%). Eleven patients experienced
      grades 2 and 3 gastrointestinal toxicity, and haematological toxicity grade 3 was
      observed in 3 patients (6%). Median time to progression was 107 days (CI 95% 85
      to 129), and median overall survival was 281 days (CI 95% 164 to 398). Third
      line, oral capecitabine in anthracycline- and taxane-pretreated metastatic breast
      cancer appears to be effective and has an acceptable toxicity profile.

PMID- 15163169
TI  - Skin toxicity as a risk factor for major infections in breast cancer patients
      treated with docetaxel.
AB  - Docetaxel-related skin toxicity, oral and gastrointestinal mucosal toxicity, and
      changes in blood cell counts were investigated as predictive factors for major
      infections in 143 women treated with 3-weekly docetaxel (100 mg/m2) as second
      line therapy for metastatic breast cancer in a randomized trial. Each patient
      with a major infection (n = 37) was compared with two controls. Skin toxicity
      (odds ratio 2.97, 95% CI 1.37-6.47), oral mucositis (1.98, CI 1.30-3.04), and the
      leukocyte nadir (0.12, CI 0.02-0.51) were significantly associated with a major
      infection in a univariate logistic regression analysis. In a multivariate
      analysis, skin toxicity was the only independent factor predictive for grade 3 to
      4 infection (2.75, CI 1.00-7.58). A major infection was diagnosed in 62% (8 out
      of 13) of the docetaxel cycles in severely (grade 4) leukopenic patients who had
      grade 2 to 4 skin toxicity. Major infections are common in leukopenic patients
      who develop docetaxel-associated skin toxicity, and leukopenic patients
      presenting with docetaxel-induced skin toxicity may be candidates for
      prophylactic anti-infection measures such as prophylactic therapy with
      hematopoietic growth factors.

PMID- 15163170
TI  - Outcome of single fraction total body irradiation-conditioned stem cell
      transplantation in younger children with malignant disease--comparison with a
      busulphan-cyclophosphamide regimen.
AB  - The logistic difficulties of using fractionated total body irradiation (TBI) in
      the youngest children often limit the choice to single fraction TBI (sfTBI) or
      non-TBI-based regimens. We retrospectively evaluated 44 such children ( < 7
      years) conditioned with either sfTBI (n = 26) or busulphan-cyclophosphamide (Bu
      Cy) (n = 18), transplanted for hematological malignancies between 1988 and 2001.
      Both neutrophil and platelet engraftment were faster in the sfTBI group with a
      similar incidence of graft failure (6.8%). Acute GVHD (graft versus host disease)
      grade 2-4 occurred in 38.4% and 38.8% and chronic GVHD in 20% and 15.4% of the
      patients in the sfTBI and Bu-Cy groups, respectively Grade 2-4 GVHD was
      associated with reduced risk of relapse (p = 0.03). This finding was more
      pronounced in high-risk patients with 2/10 relapses in patients with GVHD grade 2
      4, compared with 13/18 relapses among those with GVHD 0-1 (p = 0.05). The
      probability of overall survival was 43.3% in the sfTBI group and 33.3% in the Bu
      Cy group (p = 0.6). However, the outcomes for high-risk patients and those with
      acute lymphoblastic leukemia were better in the sfTBI group. While
      hypothyroidism, growth hormone deficiency, learning problems and cataract
      formation were observed only in the sfTBI group, early cardiac toxicity,
      behavioral problems and seizures were more common in the Bu-Cy group. Thus, where
      fractionated TBI is not feasible, sfTBI offers improved survival in high-risk
      children with acute lymphoblastic leukemia compared with Bu-Cy, without an
      unacceptable increase in early or late toxicity.

PMID- 15163171
TI  - Effects of 10alpha,25-dihydroxyvitamin D3 on doxorubicin-induced chromosomal
      aberrations in rat bone marrow cells.
AB  - The present study was carried out to evaluate the effects of 1alpha,25
      dihydroxyvitamin D3 (VD) on chromosomal aberrations induced by doxorubicin (DXR).
      Wistar rats were divided into eight experimental groups of five animals each.
      Control group animals were treated with i.p. distilled water. The animals in
      three VD groups were given only VD for 4, 6 or 8 weeks. In the DXR groups the
      animals were given only DXR. In the combination groups VD doses were given for 4,
      6 or 8 weeks for each group and DXR was injected 24 h before sacrificing the
      rats. DXR (50 mg/100 g b.w.) was injected intraperitoneally and VD by gavage 3
      microg/kg/day twice weekly. Animals treated with both VD and DXR showed a low
      frequency of chromosomal aberrations and abnormal metaphases when compared with
      animals treated with DXR alone (p < 0.0001). The numbers of both chromosomal
      aberrations and abnormal metaphases were similar in weeks 6 and 8 (p > 0.05) and
      lower than those in week 4 for the VD groups (p < 0.0001). Under the present
      experimental conditions, the efficiency of VD in protecting cells against DXR
      induced chromosome damage was found to be dose dependent. The protective effects
      of VD on chromosome aberrations induced by DXR are discussed in the light of
      literature data.

PMID- 15163173
TI  - Four testicular biopsies failing to detect a case of testicular intraepithelial
      neoplasia.

PMID- 15163172
TI  - Vinorelbine-induced acute reversible peripheral neuropathy in a patient with
      ovarian carcinoma pretreated with carboplatin and paclitaxel.

PMID- 15163174
TI  - Response of plasmacytomas to low-dose thalidomide in a patient with refractory
      multiple myeloma.

PMID- 15163175
TI  - A medicinal chemistry perspective on artemisinin and related endoperoxides.

PMID- 15163176
TI  - Synthesis and antibacterial activity of a novel class of 4'-substituted 16
      membered ring macrolides derived from tylosin.
AB  - Novel 4'-substituted 16-membered ring macrolides were synthesized by the cleavage
      of the mycarose sugar of tylosin and subsequent modification of 4'-hydroxyl
      group. This new class of macrolide antibiotics exhibited potent activity against
      some key erythromycin-resistant pathogens.

PMID- 15163177
TI  - A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are
      organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes.
      Selective targeting of delta-kappa heterodimers.
AB  - In view of recent pharmacological studies suggesting the existence of delta-kappa
      opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized
      and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series)
      containing kappa and delta antagonist pharmacophores. Pharmacological and binding
      data have provided evidence for the bridging of spinal delta-kappa receptor
      heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The
      selectivity profile of KDN-21 and the apparent absence of coupled delta(1)
      kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.

PMID- 15163178
TI  - A novel series of piperidin-4-yl-1,3-dihydroindol-2-ones as agonist and
      antagonist ligands at the nociceptin receptor.
AB  - A series of N-(4-piperidinyl)-2-indolinones were discovered as a new structural
      class of nociceptin receptor (NOP) ligands. Unlike other previously reported
      classes of NOP receptor ligands, modifications of the piperidine N substituents
      afforded both potent agonists and antagonists, with modest selectivities over
      other opioid receptors. The SAR revealed in this new series will provide
      important insights for the development of pharmacophores for agonist and
      antagonist actions at the NOP receptor.

PMID- 15163179
TI  - The PDBbind database: collection of binding affinities for protein-ligand
      complexes with known three-dimensional structures.
AB  - We have screened the entire Protein Data Bank (Release No. 103, January 2003) and
      identified 5671 protein-ligand complexes out of 19 621 experimental structures. A
      systematic examination of the primary references of these entries has led to a
      collection of binding affinity data (K(d), K(i), and IC(50)) for a total of 1359
      complexes. The outcomes of this project have been organized into a Web-accessible
      database named the PDBbind database.

PMID- 15163180
TI  - Sultam hydroxamates as novel matrix metalloproteinase inhibitors.
AB  - In this communication we describe the design, synthesis, and evaluation of novel
      sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to
      be an active inhibitor (MMP-2 IC(50) = 1 nM) with 1000-fold selectivity over MMP
      1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of
      26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active
      site.

PMID- 15163181
TI  - Antiproliferative and phenotype-transforming antitumor agents derived from
      cysteine.
AB  - Selective destruction of malignant tumor cells without damaging normal cells is
      an important goal for cancer chemotherapy in the 21st century. Differentiating
      agents that transform cancer cells to either a nonproliferating or normal
      phenotype could potentially be tissue-specific and avoid side effects of current
      drugs. However, most compounds that are presently known to differentiate cancer
      cells are histone deacetylase inhibitors that are of low potency or suffer from
      low bioavailability, rapid metabolism, reversible differentiation, and
      nonselectivity for cancer cells over normal cells. Here we describe 36
      nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C
      terminus to benzylamine, at the N-terminus to a small library of carboxylic
      acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were
      cytotoxic at nanomolar concentrations against a particularly aggressive human
      melanoma cell line (MM96L), four compounds showed selectivities of > or =5:1 for
      human melanoma over normal human cells (NFF), and four of the most potent
      compounds were further tested and found to be cytotoxic for six other human
      cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7;
      ovarian JAM, CI80-13S). The most active compounds typically caused
      hyperacetylation of histones, induced p21 expression, and reverted phenotype of
      surviving tumor cells to a normal morphology. Only one compound was given orally
      at 5 mg/kg to healthy rats to look for bioavailability, and it showed reasonably
      high levels in plasma (C(max) 6 microg/mL, T(max) 15 min) for at least 4 h.
      Results are sufficiently promising to support further work on refining this and
      related classes of compounds to an orally active, more tumor-selective, antitumor
      drug.

PMID- 15163182
TI  - Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors.
AB  - In an effort to discover potent, clinically useful thrombin inhibitors, a rapid
      analogue synthetic approach was used to explore the P(1) region. Various
      benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One
      compound with an o-thiadiazole benzylic substitution was found to have a thrombin
      K(i) of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was
      undertaken and subsequently demonstrated that the o-triazole and tetrazole rings
      were optimal. Combination of these potent P(1) aryl heterocycles with a variety
      of P(2)-P(3) groups produced a compound with an extraordinary thrombin inhibitory
      activity of 1.4 pM. It is hoped that this potency enhancement in P(1) will allow
      for more diversification in the P(2)-P(3) region to ultimately address additional
      pharmacological concerns.

PMID- 15163183
TI  - Synthesis, molecular modeling, and biological studies of novel piperidine-based
      analogues of cocaine: evidence of unfavorable interactions proximal to the 3alpha
      position of the piperidine ring.
AB  - A qualitative model for the binding pocket proximal to the 3alpha-substituent of
      the piperidine-based monoamine transporter ligands was proposed and tested. Based
      on this model, a new series of druglike 3alpha-modified piperidine-based
      analogues of cocaine were designed, synthesized, and studied for their ability to
      inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. We
      found that the insertion of at least one additional methylene group between the
      piperidine ring and the polar group in the 3alpha-substituent dramatically
      improves the activity of the compounds that are generally inactive without this
      additional linker. Molecular modeling analysis showed that the more flexible
      3alpha-substituents can avoid unfavorable interactions with the binding sites of
      DAT, SERT, and NET. The present results may have important implications for the
      elucidation of the structural differences between DA, 5-HT, and NE transporters
      and for the further design of new leads for development of cocaine abuse
      medication as well as certain neurological disorders such as ADHD and depression.

PMID- 15163184
TI  - Study on affinity profile toward native human and bovine adenosine receptors of a
      series of 1,8-naphthyridine derivatives.
AB  - A new series of 1,8-naphthyridine derivatives (29-44 and 46-52) bearing various
      substituents in different positions on the heterocyclic nucleus were synthesized
      in order to analyze the effects produced on the affinity toward the bovine
      adenosine receptors. These derivatives represent an extension of our previous
      work on this class of compounds with high affinity toward A(1) adenosine
      receptors.(19) The results of radioligand binding assays indicate that a large
      number of the 1,8-naphthyridine derivatives proved to be A(1) selective, with a
      high affinity toward bovine adenosine receptors in the low nanomolar range, and
      one (29) in the subnanomolar range. Furthermore, the new series of 1,8
      naphthyridine derivatives (29-44 and 46-52), together with the analogous
      derivatives 1-28 previously studied,(19) were tested to evaluate their affinity
      toward human cortical A(1) receptors and human striatal A(2A) receptors. The
      results indicate that all the 1,8-naphthyridine compounds generally possess a
      higher affinity toward the bovine A(1) receptor compared with the human A(1)
      receptor. As regards the affinity toward the A(2A) bovine receptor, only a few
      compounds possess a moderate affinity, which for some compounds remained
      approximately the same toward the A(2A) human receptor. A molecular modeling
      study of the docking of the 1,8-naphthyridine compounds with both the bovine and
      the human A(1) adenosine receptors was carried out with the aim of explaining the
      marked decrease in the affinity toward human A(1) adenosine receptors in
      comparison with bovine A(1) adenosine receptors. This study indicated that the
      structural differences, albeit small, of the active sites of the two receptors
      make differences in the dimensions of the site and this influenced the ability of
      the title compounds to interact with the two A(1) receptors.

PMID- 15163186
TI  - Development of a 3D model for the human cannabinoid CB1 receptor.
AB  - A novel comparison model of the human cannabinoid CB1 receptor has been
      constructed using the bovine rhodopsin X-ray structure as a template. The model
      was subjected to a 500-ps molecular dynamics simulation, and thereafter new
      conformers of the receptor model were produced in a simulated annealing
      procedure. Using an automated docking procedure, well-known cannabimimetic
      ligands were docked into six different model conformers, of which one was chosen
      for a detailed study of receptor-ligand interactions. The docking results
      confirm, for example, the importance of lysine K3.28(192) in the binding of these
      ligands. Also, other experimental data are fairly consistent with the present
      model, though there are some differences when compared to other recent CB1
      comparison models. The present model will serve as a tool to investigate the
      receptor-ligand interactions and facilitate the design of novel cannabimimetic
      drugs.

PMID- 15163185
TI  - Assessing scoring functions for protein-ligand interactions.
AB  - An assessment of nine scoring functions commonly applied in docking using a set
      of 189 protein-ligand complexes is presented. The scoring functions include the
      CHARMm potential, the scoring function DrugScore, the scoring function used in
      AutoDock, the three scoring functions implemented in DOCK, as well as three
      scoring functions implemented in the CScore module in SYBYL (PMF, Gold,
      ChemScore). We evaluated the abilities of these scoring functions to recognize
      near-native configurations among a set of decoys and to rank binding affinities.
      Binding site decoys were generated by molecular dynamics with restraints. To
      investigate whether the scoring functions can also be applied for binding site
      detection, decoys on the protein surface were generated. The influence of the
      assignment of protonation states was probed by either assigning "standard"
      protonation states to binding site residues or adjusting protonation states
      according to experimental evidence. The role of solvation models in conjunction
      with CHARMm was explored in detail. These include a distance-dependent dielectric
      function, a generalized Born model, and the Poisson equation. We evaluated the
      effect of using a rigid receptor on the outcome of docking by generating all
      pairs decoys ("cross-decoys") for six trypsin and seven HIV-1 protease complexes.
      The scoring functions perform well to discriminate near-native from misdocked
      conformations, with CHARMm, DOCK-energy, DrugScore, ChemScore, and AutoDock
      yielding recognition rates of around 80%. Significant degradation in performance
      is observed in going from decoy to cross-decoy recognition for CHARMm in the case
      of HIV-1 protease, whereas DrugScore and ChemScore, as well as CHARMm in the case
      of trypsin, show only small deterioration. In contrast, the prediction of binding
      affinities remains problematic for all of the scoring functions. ChemScore gives
      the highest correlation value with R(2) = 0.51 for the set of 189 complexes and
      R(2) = 0.43 for the set of 116 complexes that does not contain any of the
      complexes used to calibrate this scoring function. Neither a more accurate
      treatment of solvation nor a more sophisticated charge model for zinc improves
      the quality of the results. Improved modeling of the protonation states, however,
      leads to a better prediction of binding affinities in the case of the generalized
      Born and the Poisson continuum models used in conjunction with the CHARMm force
      field.

PMID- 15163187
TI  - Anti-HIV activity and conformational studies of peptides derived from the C
      terminal sequence of SDF-1.
AB  - The entry of the human immunodeficiency virus type 1 (HIV-1) into target cells
      requires the interaction of viral envelope glycoprotein, gp120, with the human
      CD4 glycoprotein and a chemokine receptor, usually CCR5 or CXCR4. The natural
      ligand for CXCR4 is the chemokine SDF-1 that inhibits entry and replication of X4
      HIV-1 strains. SDF-1 is produced in two forms, SDF-1alpha (68 residues) and SDF
      1beta (72 residues); the difference between them lies in the additional four C
      terminal amino acids in the SDF-1beta sequence. Despite the relevance of the N
      terminal site in determining the SDF anti HIV-1 activity, SDF-1beta has a
      stronger activity than SDF-1alpha. Here we demonstrate that a synthetic peptide
      mapped on the C-terminus of SDF-1beta presents inhibitory activity, whereas an
      analogue reproducing the C-terminal trait of SDF-1alpha does not show any
      activity. The opposite biological effect of the two peptides correlates with the
      type of interaction they each have with heparin and chondroitin sulfate.

PMID- 15163188
TI  - A molecular basis for the selectivity of thiadiazole urea inhibitors with
      stromelysin-1 and gelatinase-A from generalized born molecular dynamics
      simulations.
AB  - Matrix metalloproteinases (MMPs) represent a potentially important class of
      therapeutic targets for the treatment of diseases such as cancer. Selective
      inhibition of MMPs will be required given the high sequence identity across the
      family and the discovery that individual MMPs also regulate the natural
      angiogenesis inhibitor angiostatin. In this study, we have used computational
      methods to model the selectivity for six thiadiazole urea inhibitors with
      stromelysin-1 and gelatinase-A, two homologous MMPs that have been implicated in
      breast cancer. From continuum Generalized Born molecular dynamics (GB-MD) and MM
      GBSA analysis, we estimated ligand free energies of binding using 200 snapshots
      obtained from a short 40 ps simulation of the relevant protein-ligand complex.
      The MM-GBSA free energies, computed from the continuum GB-MD trajectories, show
      strong correlation with the experimental affinities (r(2) = 0.74); prior studies
      have employed explicit water MD simulations. Including estimates for changes in
      solute entropy in the binding calculations slightly diminishes the overall
      correlation with experiment (r2 = 0.71). Notably, in every case, the simulation
      results correctly predict that a given ligand will bind selectively to
      stromelysin-1 over gelatinase-A which is gratifying given the high degree of
      structural homology between the two proteins. The increased selectivity for
      stromelysin-1 appears to be driven by (1) increased favorable van der Waals
      interactions, (2) increased favorable Coulombic interactions, and (3) decreased
      unfavorable total electrostatic energies (Coulombic plus desolvation).

PMID- 15163189
TI  - Characterization of a ligand-receptor binding event using receptor-dependent four
      dimensional quantitative structure-activity relationship analysis.
AB  - Receptor-dependent four-dimensional quantitative structure-activity relationship
      (RD-4D-QSAR) analysis is used to map the ligand-receptor binding event
      characteristic of a set of 47 glucose analogue inhibitors of glycogen
      phosphorylase (GPb). Specifically, the geometric and energetic binding profiles
      are constructed, conformational changes are determined, and conformational
      couplings among structural units are identified for the composite set of ligand
      receptor complexes. A pruned ligand-receptor model is used to estimate ligand
      receptor thermodynamics. Rather than explicitly handling the large amount of
      structural data generated from each of the pruned ligand-receptor models, these
      complexes were divided into three subregions. The subregions consist of a
      "functional" region, the smallest region providing definitive information about
      inhibitor binding, and two "allosteric" regions that surround the "functional"
      region and are based on distances from the center of the catalytic site. Maximum
      information on inhibitor binding and/or inhibitor-receptor conformational changes
      is extracted from each of these subregions. The key sites for inhibitor binding
      and conformational changes in GPb are presented as grid cell occupancy
      descriptors (GCODs), which can be both numerically and graphically represented.
      An induced conformational change in both the inhibitor and the binding site of
      GPb occurs in a distinct manner for each complex. The inter-relationships
      (correlations) between GCODs from different regions are identified and probed.
      Such correlations validate the ligand-receptor interactions identified from the
      "functional" region. A long-range network of conformational associations
      involving ligands and the receptor is also found by exploring correlations among
      the GCODs for the set of inhibitors.

PMID- 15163190
TI  - New series of morpholine and 1,4-oxazepane derivatives as dopamine D4 receptor
      ligands: synthesis and 3D-QSAR model.
AB  - Since the identification of the dopamine D(4) receptor subtype and speculations
      about its possible involvement in schizophrenia, much work has been put into
      development of selective D(4) ligands. These selective ligands may be effective
      antipsychotics without extrapyramidal side effects. This work describes the
      synthesis of a new series of 2,4-disubstituted morpholines and 2,4-disubstituted
      1,4-oxazepanes with selectivity for the dopamine D(4) receptor. A 3D-QSAR
      analysis using the GRID/GOLPE methodology was performed with the purpose to get a
      better understanding of the relationship between chemical structure and
      biological activity. Inspection of the coefficient plots allowed us to identify
      that regions which are important for affinity are situated around the two benzene
      ring systems, a p-chlorobenzyl group, and the aliphatic amine belonging to the
      morpholine or 1,4-oxazepane system. In addition, the size of the morpholine or
      1,4-oxazepane ring seems to be important for affinity.

PMID- 15163192
TI  - Integrating fragment assembly and biophysical methods in the chemical advancement
      of small-molecule antagonists of IL-2: an approach for inhibiting protein-protein
      interactions.
AB  - Fragment assembly has shown promise for discovering small-molecule antagonists
      for difficult targets, including protein-protein interactions. Here, we describe
      a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2
      receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a
      compound with millimolar affinity was evolved to a hit series with low micromolar
      activity, and these compounds were optimized into a lead series with nanomolar
      affinity. Fragment assembly was useful not only for hit identification, but also
      for lead optimization. Throughout the discovery process, biophysical methods and
      structural biology demonstrated that compounds bound reversibly to IL-2 at the IL
      2 receptor binding site.

PMID- 15163191
TI  - Synthesis and quantitative structure-activity relationship of hydrazones of N
      amino-N'-hydroxyguanidine as electron acceptors for xanthine oxidase.
AB  - A series of new N-hydroxyguanidines were synthesized and tested for electron
      acceptor activity on bovine milk xanthine oxidase using xanthine as reducing
      substrate. Manual inspection of the structure-activity data revealed that
      molecules containing nitro groups ("set A") show a different structure-activity
      relationship pattern compared to non-nitro compounds ("set B"). Accordingly
      separate QSAR models were built and validated for the two sets. Substantial
      differences were found in properties governing acceptor activity for the models,
      the only common property being sterical access to the imino nitrogen atom of the
      hydroxyguanidinimines. For set A molecules the presence of a nitro substituent at
      a certain distance range from the hydroxuguanidino group was most important. In
      addition, the presence of a nitro group in the ortho position interacting with
      NH(2) of the hydroxyguanidino group, and the mutual geometry of the phenyl ring,
      hydroxyguanidine, and imine groups was important for this set. By contrast, for
      set B molecules the acceptor activity was most influenced by the geometry of
      methoxy groups and the size and geometry of meta and para substituents of the
      phenyl ring.

PMID- 15163193
TI  - Conformationally constrained peptide analogues of pTyr-Glu-Glu-Ile as inhibitors
      of the Src SH2 domain binding.
AB  - A series of conformationally constrained peptides were designed and synthesized
      as the Src SH2 domain ligands based on a tetrapeptide sequence pTyr-Glu-Glu-Ile
      (pYEEI). In general, the constrained peptides such as compounds 6, 7, and 11
      (IC(50) = 1.1-1.5 microM) showed higher binding affinities to the Src SH2 domain
      relative to the corresponding linear peptides 8a, 9a, and 13a, respectively
      (IC(50) > 100 microM), and pYEEI (IC(50) = 6.5 microM), as evaluated by a
      fluorescence polarization assay. Molecular modeling studies revealed that in
      constrained peptides, the isoleucine side chain penetrates very deeply into the
      hydrophobic binding pocket (P + 3 site) of the Src SH2 domain. These constrained
      peptides can serve as novel templates for the design of small and nonpeptidic
      inhibitors of the Src SH2 domain.

PMID- 15163194
TI  - SDOCKER: a method utilizing existing X-ray structures to improve docking
      accuracy.
AB  - This paper introduces a new strategy for structure-based drug design that
      combines high-quality docking with data from existing ligand-protein cocrystal X
      ray structures. The main goal of SDOCKER, a new algorithm that implements this
      strategy, is docking accuracy improvement. In this new paradigm, simulated
      annealing molecular dynamics is used for conformational sampling and optimization
      and an additional similarity force is applied on the basis of the positions of
      ligands from X-ray data that focus the sampling on relevant regions of the active
      site. Because the structural information from both the ligand and protein active
      site is included, this approach is more effective in finding the optimal
      conformation for a ligand-protein complex than the classical docking or
      similarity overlays. Interestingly, it was found that a 3D similarity-only
      approach gives comparable docking accuracy to the regular force field approach
      used in classical docking, given the final structures are minimized in the
      presence of the protein. The combination of both, as implemented in SDOCKER, is
      shown here to be more accurate. A significant improvement in docking accuracy has
      been observed for three different test systems. Specifically an improvement of
      10%, 17.5%, and 10% is seen for 37 HIV-1 protease, 32 thrombin, and 23 CDK2
      ligands, respectively, compared to docking using the force field alone. In
      addition, SDOCKER's accuracy performance dependence on the similarity template is
      discussed. The strategy of utilizing existing ligand X-ray information should
      prove effective in light of the multitude of structures available from structural
      genomics approaches.

PMID- 15163195
TI  - Design, synthesis, anti-HIV activities, and metabolic stabilities of
      alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors.
AB  - The alkenyldiarylmethane (ADAM) HIV-1 non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) are effective anti-HIV agents in cell culture. However, the
      potential clinical utility of the ADAMs is expected to be limited by the presence
      of methyl ester moieties that are likely to be metabolized by nonspecific
      esterases in blood plasma to biologically inactive carboxylic acid derivatives.
      The present investigation was therefore undertaken to investigate the anti-HIV
      activities of the ADAMs versus HIV-1(IIIB) and HIV-2(ROD) in MT-4 cells and the
      stabilities of the biologically active ADAMs in rat plasma. The ADAMs displayed a
      wide range of metabolic stabilities in rat plasma, with half-lives ranging from
      0.9 to 76.6 min. A wide assortment of structural modifications was tolerated,
      with 18 of the 32 compounds tested displaying EC(50) values between 0.3 and 3.7
      microM versus HIV-1(IIIB) in MT-4 cells, 3 compounds in the EC(50) = 13.2-35.4
      microM range, and the remaining compounds inactive. Consistent with the mechanism
      of action of the ADAMs as NNRTIs, they were inactive or displayed comparatively
      low activity versus HIV-2(ROD). The replacement of the two aromatic methyl ester
      substituents in one of the most active ADAMs (EC(50) = 0.6 microM) with two
      methyl thioester groups resulted in an increase in plasma half-life from 5.8 to
      55.3 min, while maintaining the antiviral potency at the EC(50) = 1.8 microM
      level. At the same time, the bis(thioester) modification was less cytotoxic to
      uninfected MT-4 cells, with a CC(50) of >224 microM versus 160 microM for the
      parent compound.

PMID- 15163197
TI  - Synthesis and structure-activity relationships of a novel series of tricyclic
      dihydropyridine-based KATP openers that potently inhibit bladder contractions in
      vitro.
AB  - Structure-activity relationships were investigated on a novel series of tricyclic
      dihydropyridine-containing K(ATP) openers. This diverse group of analogues,
      comprising a variety of heterocyclic rings fused to the dihydropyridine nucleus,
      was designed to determine the influence on activity of hydrogen-bond-donating and
      -accepting groups and their stereochemical disposition. Compounds were evaluated
      for K(ATP) activity in guinea pig bladder cells using a fluorescence-based
      membrane potential assay and in a pig bladder strip assay. The inhibition of
      spontaneous bladder contractions in vitro was also examined for a subset of
      compounds. All compounds studied showed greater potency to inhibit spontaneous
      bladder contractions relative to their potencies to inhibit contractions elicited
      by electrical stimulation.

PMID- 15163198
TI  - Chemometric studies on the bactericidal activity of quinolones via an extended
      VolSurf approach.
AB  - An extended VolSurf approach, that additionally includes SHAPE descriptors, was
      applied to a dataset of 55 quinolones. Bactericidal activity was measured at
      Bayer AG, Germany, for Gram-negative (Escherichia coli and Pseudomonas
      aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Enterococcus
      faecalis). Chemometric analysis was first approached via a classical VolSurf
      approach. The following descriptors were found most important: bactericidal
      activity particularly increases with high values of the best volume (BV11(OH2))
      and the minimum energy (Emin1(OH2)) of the water probe, high values of the integy
      moment (ID(DRY)) of the lipophilic probe, and high values of the hydrophilic
      region (W(O)) of the hydrogen bond acceptor probe. Best volume (BV31(OH2)) of the
      water probe and best volume (BV12(DRY)) and lipophilic regions (D(DRY)) of the
      lipophilic probe as well as H-bonding capacity derived with the CO probe (HB(O))
      are inversely related to activity. PLS analysis yields a five-component model
      with an r(2) of 0.83 and a q(2) of 0.43 after variable selection via fractional
      factorial design (FFD). Chemometric modeling could be improved by including newly
      derived SHAPE descriptors, which were merged with the VolSurf descriptors and
      subjected to PLS analysis. The global model of this extended VolSurf approach is
      optimal with two components and exhibits a significantly improved statistical
      quality; a marginally reduced r(2) (0.75 versus 0.83) is more than compensated by
      a highly improved predictivity with a q(2) of 0.63 versus 0.43. To prove model
      quality, external prediction of seven test set quinolones was performed. The
      precise prediction of all test set molecules nicely demonstrates the robustness
      and statistical significance of the obtained chemometric model using the extended
      VolSurf approach.

PMID- 15163196
TI  - Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9
      hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers:
      discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2
      b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that
      selectively inhibits spontaneous bladder contractions.
AB  - Structure-activity relationships were investigated on a novel series of
      sulfonyldihydropyridine-containing K(ATP) openers. Ring sizes, absolute
      stereochemistry, and aromatic substitution were evaluated for K(ATP) activity in
      guinea pig bladder cells using a fluorescence-based membrane potential assay and
      in a pig bladder strip assay. The inhibition of spontaneous bladder contractions
      in vitro was also examined for a select group of compounds. All compounds studied
      showed greater potency to inhibit spontaneous bladder contractions relative to
      their potencies to inhibit contractions elicited by electrical stimulation. In an
      anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)
      cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at
      plasma concentrations lower than those that affected hemodynamic parameters.
      Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and
      supports the concept that bladder-selective K(ATP) channel openers may have
      utility in the treatment of overactive bladder.

PMID- 15163199
TI  - Arylcyanoguanidines as activators of Kir6.2/SUR1K ATP channels and inhibitors of
      insulin release.
AB  - Phenylcyanoguanidines substituted with lipophilic electron-withdrawing functional
      groups, e.g. N-cyano-N'-[3,5-bis-(trifluoromethyl)phenyl]-N' '
      (cyclopentyl)guanidine (10) and N-cyano-N'-(3,5-dichlorophenyl)-N' '-(3
      methylbutyl)guanidine (12) were synthesized and investigated for their ability to
      inhibit insulin release from beta cells, to repolarize beta cell membrane
      potential, and to relax precontracted rat aorta rings. Structural modifications
      gave compounds, which selectively inhibit insulin release from betaTC6 cells
      (e.g. compound 10: IC(50) = 5.45 +/- 1.9 microM) and which repolarize betaTC3
      beta cells (10: IC(50) = 4.7 +/- 0.5 microM) without relaxation of precontracted
      aorta rings (10: IC(50) > 300 microM). Inhibition of insulin release from rat
      islets was observed in the same concentration level as for betaTC6 cells (10:
      IC(50) = 1.24 +/- 0.1 microM, 12: IC(50) = 3.8 +/- 0.4 microM). Compound 10 (10
      microM) inhibits calcium outflow and insulin release from perifused rat
      pancreatic islets. The mechanisms of action of 10 and 12 were further
      investigated. The compounds depolarize mitochondrial membrane from smooth muscle
      cells and beta cell and stimulate glucose utilization and mitochondrial
      respiration in isolated liver cells. Furthermore, 10 was studied in a patch clamp
      experiment and was found to activate Kir6.2/SUR1 and inhibit Kir6.2/SUR2B type of
      K(ATP) channels. These studies indicate that the observed effects of the
      compounds on beta cells result from activation of K(ATP) channels of the cell
      membrane in combination with a depolarization of mitochondrial membranes. It also
      highlights that small structural changes can dramatically shift the efficacy of
      the cyanoguanidine type of selective activators of Kir6.2/SUR2 potassium
      channels.

PMID- 15163200
TI  - Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone
      cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei,
      and Trypanosoma cruzi.
AB  - We have synthesized a library of thiosemicarbazones and screened them against
      three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and
      against the respective parasite sources of these three proteases, Trypanosoma
      cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified
      compounds that were effective against the enzymes and the parasites but also some
      compounds that were parasiticidal despite a lack of activity against the
      proteases. Several compounds were effective in killing all tested parasites.
      These promising lead compounds were tested for general toxicity in mice, and only
      one produced observable toxicity after 62 h. Our results suggest that
      thiosemicarbazones represent validated drug leads that kill several species of
      protozoan parasites through the inhibition of cysteine proteases as well as other
      novel targets.

PMID- 15163202
TI  - Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant
      enzymes for indigoid synthesis.
AB  - Indigoids, a class of bis-indoles, represent a promising protein kinase inhibitor
      scaffold. Oxidation of indole by cytochrome P450 (P450) has been shown to
      generate species (indoxyl, isatin) that couple to yield indigo and indirubin.
      Escherichia coli-expressed human P450 2A6 mutants isolated from a randomized
      library were incubated with 27 substituted indole derivatives. Extracts of the
      cultures were screened for inhibition of human cyclin-dependent kinases (CDK)-1
      and -5 and glycogen synthase kinase-3 (GSK3). The extracts from cultures
      incubated with 5-methoxyindole were the most inhibitory. High-performance liquid
      chromatography (HPLC) separation yielded a mixture of seven colored indigoids.
      These indigoids included indigo, indirubin, the di(5-methoxy) derivatives of
      indigo and indirubin, and both of the possible mono 5-methoxy derivatives of
      indirubin, which were all identified by visible, mass, and NMR spectra. Cultures
      with 5-methylindole added to the media also yielded inhibitory material, and 5-
      and 5'-methylindirubin were characterized. The most inhibitory of these indigoids
      were the monosubstituted indirubins and 5,5'-dimethoxyindirubin, which was > or
      =10x more active than indirubin. Thus, the overall approach involves the use of a
      library of randomized enzyme mutants to activate component moieties of a desired
      set of larger molecules, thus yielding a library of drug candidates that can be
      screened and characterized. The general strategy may have additional
      applications.

PMID- 15163201
TI  - Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8
      tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing alpha(1A)
      adrenoceptor agonist.
AB  - Structure-activity studies were performed on the alpha(1A)-adrenoceptor (AR)
      selective agonist N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1
      naphthalenyl]methanesulfonamide (4). Compounds were evaluated for binding
      activity at the alpha(1A), alpha(1b), alpha(1d), alpha(2a), and alpha(2B)
      subtypes. Functional activity in tissues containing the alpha(1A) (rabbit
      urethra), alpha(1B) (rat spleen), alpha(1D) (rat aorta), and alpha(2A) (rat
      prostatic vas deferens) was also evaluated. A dog in vivo model simultaneously
      measuring intraurethral pressure (IUP) and mean arterial pressure (MAP) was used
      to assess the uroselectivity of the compounds. Many of the compounds that were
      highly selective in vitro for the alpha(1A)-AR subtype were also more
      uroselective in vivo for increasing IUP over MAP than the nonselective alpha(1)
      agonists phenylpropanolamine (PPA) (1) and ST-1059 (2, the active metabolite of
      midodrine), supporting the hypothesis that greater alpha(1A) selectivity would
      reduce cardiovascular side effects. However, the data also support a prominent
      role of the alpha(1A)-AR subtype in the control of MAP.

PMID- 15163203
TI  - Synthesis and biological evaluation of 14-alkoxymorphinans. 21. Novel 4-alkoxy
      and 14-phenylpropoxy derivatives of the mu opioid receptor antagonist cyprodime.
AB  - The synthesis, biological, and pharmacological evaluation of novel derivatives of
      cyprodime are described. Their binding affinities at mu, delta, and kappa opioid
      receptors were evaluated using receptor binding assay. It was observed that the
      affinity of these compounds was sensitive to the character and length of the
      substituent in position 4. Further prolongation of the 4-alkoxy group of
      cyprodime (1) and its 4-butoxy analogue 2 is detrimental for the mu opioid
      receptor affinity. Introduction of an arylalkoxy group at C-4 does not increase
      mu affinity in the case of benzyloxy, while a phenylpropoxy group reduces mu
      affinity. The delta and kappa affinities were also reduced compared to the
      reference compounds. A significant increase in the affinity at the mu opioid
      receptors was achieved by introducing a 14-phenylpropoxy group. Increases in the
      affinity at delta and kappa receptors were also observed. These findings provide
      further evidence that the nature of the substituent at position 14 has a major
      impact on the abilities of morphinans to interact with opioid receptors. In the
      [(35)S]GTPgammaS binding assay, all tested compounds were partial agonists at mu
      and delta receptors. Compounds 8 and 17 showed antagonism at kappa receptors,
      while compound 7 exhibited some partial agonist activity at this receptor. The
      novel derivatives of cyprodime containing a 14-phenylpropoxy group acted as
      potent antinociceptives. When tested in vivo, compounds 7, 8, and 17 were
      considerably more potent than morphine, with phenol 7 showing the highest
      antinociceptive potency (21-fold in the hot plate test, 38-fold in the tail flick
      test, and 300-fold in the paraphenylquinone writhing test) in mice. Introduction
      of a 14-phenylpropoxy substituent leads to a profound alteration in the
      pharmacological profile of this class of compounds.

PMID- 15163204
TI  - Conformationally constrained analogues of diacylglycerol. 21. A solid-phase
      method of synthesis of diacylglycerol lactones as a prelude to a combinatorial
      approach for the synthesis of protein kinase C isozyme-specific ligands.
AB  - A solid-phase method for the synthesis of diacylglycerol lactones as protein
      kinase C ligands was developed, and a small array of nine compounds were selected
      with the idea of testing this methodology and forecasting the reliability of the
      biological data as a preamble for the construction of large chemical libraries to
      be synthesized under the same conditions. The process started with the loading of
      5-(hydroxymethyl)-5-[(4-methoxyphenoxy)methyl]-3,4,5-trihydrofuran-2-one (1) to a
      3,4-dihydro-2H-pyran resin packed inside IRORI MacroKan reactors. The elements of
      diversity were introduced at the alpha-alkylidene (R(1)) and acyl (R(2))
      positions using a set of three different aldehydes and three different acid
      chlorides, respectively. An LDA-mediated aldol condensation with R(1)CHO in the
      presence of ZnCl(2) followed by a DBU-catalyzed elimination of the triflate of
      the resulting aldol gave the alpha-alkylidene intermediates as mixtures of
      geometric isomers. Removal of the aryl-protecting group followed by acylation
      with R(2)COCl introduced the second element of diversity. Acid-assisted cleavage
      of the compounds from the resin afforded the final targets. The biological
      results obtained using the crude samples directly obtained from the resin
      compared well with those from pure materials, as the K(i) values between the two
      sets varied only by a factor between 1.5 and 3.7.

PMID- 15163205
TI  - (2R)-2-ethylchromane-2-carboxylic acids: discovery of novel PPARalpha/gamma dual
      agonists as antihyperglycemic and hypolipidemic agents.
AB  - A series of chromane-2-carboxylic acid derivatives was synthesized and evaluated
      for PPAR agonist activities. A structure-activity relationship was developed
      toward PPARalpha/gamma dual agonism. As a result, (2R)-7-(3-[2-chloro-4-(4
      fluorophenoxy)phenoxy]propoxy)-2-ethylchromane-2-carboxylic acid (48) was
      identified as a potent, structurally novel, selective PPARalpha/gamma dual
      agonist. Compound 48 exhibited substantial antihyperglycemic and hypolipidemic
      activities when orally administered in three different animal models: the db/db
      mouse type 2 diabetes model, a Syrian hamster lipid model, and a dog lipid model.

PMID- 15163206
TI  - Meta-substituted aryl(thio)ethers as potent partial agonists (or antagonists) for
      the histamine H3 receptor lacking a nitrogen atom in the side chain.
AB  - 4-(3-Aryloxypropyl)-1H-imidazoles, which possess a meta-positioned substituent in
      the aryl ring, have been synthesized and tested for activity at histamine H(3)
      receptors. The compounds having a CN, Me, or Br substituent were found to be
      antagonists, whereas CF(3), Et, i-Pr, t-Bu, COCH(3), or NO(2) substituents
      remarkably afforded partial agonists when tested in vitro on rat cerebral cortex
      synaptosomes for inhibition of [(3)H]histamine release. The compounds were also
      active in vivo, and furthermore, the CF(3)-substituted compound trifluproxim (UCL
      1470, 7) acted as a potent full agonist in vivo, having ED(50) = 0.6 +/- 0.3
      mg/kg per os in mice for inhibition of brain N(tau)-methylhistamine formation.
      Related structures have also been investigated; homologues 4-[4-(3
      (trifluoromethyl)phenoxy)butyl]-1H-imidazole and 4-[2-(3
      (trifluoromethyl)phenylthio)ethyl]-1H-imidazole are shown to be partial agonists,
      whereas the O isostere 4-[2-(3-(trifluoromethyl)phenoxy)ethyl]-1H-imidazole is an
      antagonist as is the S homologue 4-[3-(3-(trifluoromethyl)phenylthio)propyl]-1H
      imidazole and its CH(2) isostere 4-[4-(3-(trifluoromethyl)phenyl)butyl]-1H
      imidazole.

PMID- 15163207
TI  - Targeting the polyamine pathway with transition-state analogue inhibitors of 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 latter stages of polyamine biosynthesis (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. Potent inhibitors of MTAP might allow the
      buildup of sufficient levels of MTA to generate feedback inhibition of polyamine
      biosynthesis. We have designed and synthesized a family of potential transition
      state analogue inhibitors of MTAP on the basis of our knowledge of the transition
      state structure of purine nucleoside phosphorylase and the assumption that it is
      likely the two enzymes share a common catalytic mechanism. Several of the
      inhibitors display slow-onset tight-binding properties, consistent with them
      being transition-state analogues, with the most potent having a dissociation
      constant of 166 pM.

PMID- 15163208
TI  - Design, synthesis, and structure-activity relationships of haloenol lactones:
      site-directed and isozyme-selective glutathione S-transferase inhibitors.
AB  - Overexpression of glutathione S-transferase (GST), particularly the GST-pi
      isozyme, has been proposed to be one of the biochemical mechanisms responsible
      for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST
      has been suggested as an approach to combat GST-induced drug resistance. 3
      Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site
      directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of
      cisplatin on tumor cells. As an initial step to develop more potent and more
      selective haloenol lactone inactivators of GST-pi, we examined the relationship
      between the chemical structures of haloenol lactone derivatives and their GST
      inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized
      to probe the effects of (1) halogen electronegativity, (2) electron density of
      aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5)
      aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each
      compound was determined by time-dependent inhibition tests, and recombinant human
      GST-pi was used to determine their inhibitory activity. Our structure-activity
      relationship studies demonstrated that (1) reactivity of the halide leaving group
      plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic
      electron density may have some influence on the potency of GST inactivation, (3)
      high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely
      proportional to enzyme inactivation, and (5) an unsaturated system may be
      important for enzyme inhibition. This work facilitated understanding of the
      interaction of GST-pi with haloenol lactone derivatives as site-directed and
      isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

PMID- 15163209
TI  - Aziridinyldinitrobenzamides: synthesis and structure-activity relationships for
      activation by E. coli nitroreductase.
AB  - The 5-aziridinyl-2,4-dinitrobenzamide CB 1954 is a substrate for the oxygen
      insensitive nitroreductase (NTR) from E. coli and is in clinical trial in
      combination with NTR-armed adenoviral vectors in a GDEPT protocol; CB 1954 is
      also of interest for selective deletion of NTR-marked cells in normal tissues.
      Since little further drug development has been carried out around this lead, we
      report here the synthesis of more soluble variants and regioisomers and structure
      activity relationship (SAR) studies. The compounds were primarily prepared from
      the corresponding chloro(di)nitroacids through amide side chain elaboration and
      subsequent aziridine formation. One-electron reduction potentials [E(1)],
      determined by pulse radiolysis, were around -400 mV, varying little for
      aziridinyldinitrobenzamide regioisomers. Cytotoxicity in a panel of NTR
      transfected cell lines showed that in the CB 1954 series there was considerable
      tolerance of substituted CONHR side chains. The isomeric 2-aziridinyl-3,5
      dinitrobenzamide was also selective toward NTR+ve lines but was approximately 10
      fold less potent than CB 1954. Other regioisomers were too insoluble to evaluate.
      While CB 1954 gave both 2- and 4-hydroxylamine metabolites in NTR+ve cells,
      related analogues with substituted carboxamides gave only a single hydroxylamine
      metabolite possibly because the steric bulk in the side chain constrains binding
      within the active site. CB 1954 is also a substrate for the two-electron
      reductase DT-diaphorase, but all of the other aziridines (regioisomers and close
      analogues) were poorer substrates with resulting improved specificity for NTR.
      Bystander effects were determined in multicellular layer cocultures and showed
      that the more hydrophilic side chains resulted in a modest reduction in bystander
      killing efficiency. A limited number of analogues were tested for in vivo
      activity, using a single ip dose to CD-1 nude mice bearing WiDr-NTR(neo) tumors.
      The most active of the CB 1954 analogues was a diol derivative, which showed a
      substantial median tumor growth delay (59 days compared with >85 days for CB
      1954) in WiDr xenografts comprising 50% NTR+ve cells. The diol is much more
      soluble and can be formulated in saline for administration. The results suggest
      there may be advantages with carefully selected analogues of CB 1954; the weaker
      bystander effect of its diol derivative may be an advantage in the selective cell
      ablation of NTR-tagged cells in normal tissues.

PMID- 15163212
TI  - Development of a new type of allosteric modulator of muscarinic receptors:
      hybrids of the antagonist AF-DX 384 and the hexamethonio derivative W84.
AB  - Various fragments of the hexamethonio-type allosteric agent W84 were linked to
      the secondary amino group of the muscarinic M(2) acetylcholine receptor
      preferring antagonist AF-DX 384 to increase the area of attachment with the
      allosteric site. Addition of only the phthalimido moiety of W84 gave an
      allosteric enhancer of NMS binding. Thus, a new lead structure for the
      development of allosteric enhancers of NMS binding has been discovered.

PMID- 15163211
TI  - 2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors.
      Differential binding modes dependent on nitrogen substitution.
AB  - 4-Methylaminopyridine (4-MAP) (5) is a potent but nonselective nitric oxide
      synthase (NOS) inhibitor. While simple N-methylation in this series results in
      poor activity, more elaborate N-substitution such as with 4-piperidine carbamate
      or amide results in potent and selective inducible NOS inhibition. Evidently, a
      flipping of the pyridine ring between these new inhibitors allows the piperidine
      to interact with different residues and confer excellent selectivity.

PMID- 15163210
TI  - Mitomycin dimers: polyfunctional cross-linkers of DNA.
AB  - The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer
      chemotherapeutic agent, were synthesized in which two MC molecules were linked
      with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers,
      respectively. The dimeric mitomycins were designed to react as polyfunctional DNA
      alkylators, generating novel types of DNA damage. To test this design, their in
      vitro DNA alkylating and interstrand cross-linking (ICL) activities were studied
      in direct comparison with MC, which is itself an ICL agent. Evidence is presented
      that 3-5 multifunctionally alkylate and cross-link extracellular DNA and form DNA
      ICLs more efficiently than MC. Reductive activation, required for these
      activities, is catalyzed by the same reductases and chemical reductants that
      activate MC. Dimer 5, but not MC, cross-linked DNA under activation by low pH
      also. Sequence specificities of cross-linking of a 162-bp DNA fragment (tyrT DNA)
      by MC, 3, and 5 were determined using DPAGE. The dimers and MC cross-linked DNA
      with the same apparent CpG sequence specificity, but 5 exhibited much greater
      cross-linking efficacy than MC. Greatly enhanced regioselectivity of cross
      linking to G.C rich regions by 5 relative to MC was observed, for which a
      mechanism unique to dimeric MCs is proposed. Covalent dG adducts of 5 with DNA
      were isolated and characterized by their UV and mass spectra. Tri- and
      tetrafunctional DNA adducts of 5 were detected. Although the dimers were
      generally less cytotoxic than MC, dimer 5 was highly and uniformly cytotoxic to
      all 60 human tumor cell cultures of the NCI screen. Its cytotoxicity to EMT6
      tumor cells was enhanced under hypoxic conditions. These findings together verify
      the expected features of the MC dimers and warrant further study of the
      biological effects of dimer 5.

PMID- 15163213
TI  - Pathologic quiz case: a multicystic mass of the pancreatic body in a 70-year-old
      man. Serous microcystic adenoma of the pancreas.

PMID- 15163214
TI  - Pathologic quiz case: a 70-year-old man with bladder outflow obstruction.
      Prostatic stromal sarcoma.

PMID- 15163215
TI  - Pathologic quiz case: repeated positive ethylene glycol levels by gas
      chromatography. Central venous line contamination of blood samples by propylene
      glycol from intravenous lorazepam injections.

PMID- 15163216
TI  - Pathologic quiz case: a 63-year-old renal transplant recipient with a sore
      throat. Posttransplantation lymphoproliferative disorder, plasmacytoma type, with
      prominent Russell body formation.

PMID- 15163218
TI  - Cystic adrenal lymphangioma.

PMID- 15163219
TI  - Displaced bacterial colonies indicating Strongyloides larval migration on agar
      plates.

PMID- 15163220
TI  - Cutaneous anthrax.

PMID- 15163221
TI  - Pathologic quiz case: a 15-year-old girl with an intracranial midline mass.
      Pineoblastoma, World Health Organization Grade IV.

PMID- 15163222
TI  - Pathologic quiz case: an abdominopelvic mass in a 13-year-old adolescent girl.
      Predominantly mature cystic teratoma with minimal immature neuroglia and
      gliomatosis peritonei.

PMID- 15163223
TI  - Pathologic quiz case: a woman with abdominal fullness. Adrenal myelolipoma.

PMID- 15163224
TI  - Pathologic quiz case: a 10-year-old boy with weakness, lethargy, and edema.
      Arrhythmogenic right ventricular cardiomyopathy, cardiomyopathic pattern.

PMID- 15163225
TI  - Laboratory and clinical aspects of B-type natriuretic peptides.

PMID- 15163226
TI  - Clear cell ductal adenocarcinoma of pancreas: a case report and review of the
      literature.
AB  - We present a unique carcinoma of the pancreas with predominantly clear cell
      morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal
      and intracytoplasmic mucin. Immunohistochemically, the cells were positive for
      the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for
      cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen.
      Stains for the neuroendocrine markers synaptophysin and chromogranin were
      negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional
      outstanding feature was the presence of dense intraluminal and intracytoplasmic
      hyaline globules, which were immunohistochemically positive for alpha1
      antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon
      12, providing molecular evidence of ductal origin. In the proper morphologic
      context supported by immunohistochemistry, clear cell carcinoma can be regarded
      as a rare variant of ductal adenocarcinoma.

PMID- 15163227
TI  - A 59-year-old woman with immunotactoid glomerulopathy, heavy-chain disease, and
      non-hodgkin lymphoma.
AB  - Immunotactoid glomerulopathy is one of several renal disorders characterized by
      the extracellular deposition of nonamyloid fibrillary deposits. There is
      considerable debate as to whether immunotactoid glomerulopathy should be
      distinguished from fibrillary glomerulonephritis, a closely related entity.
      Currently, the distinction is based on fibril size and arrangement. We report the
      case of a 59-year-old woman in whom a diagnosis of immunotactoid glomerulopathy
      was made after a 2-year history of proteinuria. Electron microscopy of her renal
      biopsy showed randomly arranged microtubular subepithelial and mesangial
      deposits, which measured 34 nm in average diameter. She was later discovered to
      have circulating immunoglobulin G heavy chains without associated light chains
      (gamma-heavy-chain disease) and, subsequently, non-Hodgkin lymphoma, follicular
      lymphoma, grade I (World Health Organization classification). Approximately 100
      cases of gamma-heavy-chain disease have been reported in the literature since it
      was originally described by Franklin in 1964. However, while there are 10 reports
      in the literature of heavy-chain disease with fibrillary deposits in the kidney,
      none fit the criteria for immunotactoid glomerulopathy.

PMID- 15163228
TI  - Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical,
      and ultrastructural study of a case and review of the literature.
AB  - Malignant melanoma is known to display tremendous histologic diversity. One rare
      variant is the rhabdoid phenotype, so called because of the appearance of cells
      resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We
      present the histologic, immunohistochemical, and ultrastructural features of a
      malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man
      presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion,
      extensive workup failed to reveal a primary tumor site. Histologic sections
      showed a mass composed entirely of polygonal neoplastic cells with prominent
      nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly
      immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive
      with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3,
      cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen,
      smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30,
      CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and
      glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of
      intermediate filaments containing entrapped rough endoplasmic reticulum,
      mitochondria, and lipid. Recognition of this rare variant of malignant melanoma
      is important in the evaluation of tumors with rhabdoid morphology.

PMID- 15163229
TI  - Myocardial involvement in Erdheim-Chester disease.
AB  - Erdheim-Chester disease (lipoid granulomatosis) is a rare type II (non-Langerhans
      cell) histiocytosis with systemic manifestations. The disease causes nonspecific
      disturbances in the function of multiple extraosseous organs, most commonly the
      eyes, lungs, pituitary gland, and kidneys. Diagnosis is usually made on the basis
      of radiologic evidence of cortical expansion of long bones. While the osseous and
      systemic changes have been well documented in the current literature, pathologic
      changes in the myocardium have not been well characterized since Erdheim and
      Chester's first description of this disease in 1930. In the 2 autopsy cases from
      Dartmouth-Hitchcock Medical Center (Lebanon, NH) reported in the present study,
      myocardial involvement was severe and had contributed significantly to the
      patients' morbidity and death. We describe the autopsy results and correlate them
      with Erdheim's original descriptions of this disease. In neither of our cases was
      bony involvement characteristic of the disease, and the diagnosis was made
      postmortem on the basis of soft tissue findings at autopsy.

PMID- 15163230
TI  - Kaposiform hemangioendothelioma associated with nonimmune fetal hydrops.
AB  - We describe the case of a 31-week fetus who died in utero with an invasive
      retroperitoneal kaposiform hemangioendothelioma. This rare vascular neoplasm
      usually presents as a localized violaceous skin lesion in infants and behaves in
      a benign fashion; however, kaposiform hemangioendothelioma may present as an
      invasive neoplasm of the chest or abdominal cavity, where it can lead to the
      Kasabach-Merritt syndrome, which consists of thrombocytopenia, consumptive
      coagulopathy, and microangiopathic anemia in association with a vascular anomaly.
      The case we describe is unique in that the tumor presented in utero and led to
      intrauterine nonimmune fetal hydrops. Kaposiform hemangioendothelioma has been
      described in utero; however, to our knowledge, intrauterine fetal death as a
      direct consequence has not been reported previously in the literature.

PMID- 15163231
TI  - Polarizable placental particles: a case study and brief review of the literature.
AB  - Two otherwise healthy pregnant women presented with intrauterine fetal demise and
      underwent unremarkable induction of labor. Histopathologic examination of both
      placentas revealed polarizable foreign material with minimal associated tissue
      reaction in the membranes and adjacent maternal decidua. No overt foreign body
      giant cell reaction or inflammation was seen, suggesting recent introduction of
      the material. Further review of the histories showed that both women had
      undergone cervical ripening with laminaria. These are strips of collagenous
      seaweed placed in a closed cervix, where they absorb moisture and swell, dilating
      the cervix and hastening the onset of labor. Microscopic examination and
      polarization of known laminaria fragments identified this substance as the likely
      source of the polarizable material within the placental membranes. Laminaria
      fragments should be distinguished from other polarizable materials such as talc,
      suture, and retained foreign bodies on the basis of their histologic appearance
      and the acute nature of the accompanying tissue reaction.

PMID- 15163234
TI  - Clostridium botulinum and the clinical laboratorian: a detailed review of
      botulism, including biological warfare ramifications of botulinum toxin.
AB  - OBJECTIVE: This review article is designed to thoroughly familiarize all health
      care professionals with the history, classification, epidemiology, clinical
      characteristics, differential diagnosis, diagnostic evaluation (including
      laboratory-based testing), treatment, and prognosis of botulism. It is especially
      targeted toward clinical laboratorians and includes a detailed enumeration of the
      important clinical laboratory contributions to the diagnosis, treatment, and
      monitoring of patients with botulism. Finally, the bioterrorism potential for
      botulism is discussed, with an emphasis on the clinical laboratory ramifications
      of this possibility. DATA SOURCES: Included medical periodicals and textbooks
      accessioned from computerized and manual medical literature searches. More than
      1000 medical works published from the 1800s through 2003 were retrieved and
      reviewed in this process. DATA SYNTHESIS: Pertinent data are presented in textual
      and tabular formats, the latter including 6 tables presenting detailed
      information regarding the clinical parameters, differential diagnosis, diagnostic
      studies, laboratory testing, and therapeutic approaches to botulism. CONCLUSIONS:
      Because botulism is such a rare disease, a keen awareness of its manifestations
      and prompt diagnosis are absolutely crucial for its successful treatment. The
      bioterrorism potential of botulism adds further urgency to the need for all
      health care professionals to be familiar with this disease, its proper
      evaluation, and timely treatment; the need for such urgency clearly includes the
      clinical laboratory.

PMID- 15163232
TI  - Determination of plasma glycoprotein 2 levels in patients with pancreatic
      disease.
AB  - CONTEXT: Blood tests possessing higher diagnostic accuracy are needed for all the
      major pancreatic diseases. Glycoprotein 2 (GP2) is a protein that is specifically
      expressed by the pancreatic acinar cell and that has previously shown promise as
      a diagnostic marker in animal models of acute pancreatitis. OBJECTIVE: This study
      describes the development of an assay for GP2, followed by the determination of
      plasma GP2 levels in patients with acute pancreatitis, chronic pancreatitis, and
      pancreatic cancer. DESIGN: Rabbit polyclonal antisera and mouse monoclonal
      antibodies were generated against human GP2 and used to develop an enzyme-linked
      immunosorbent assay. The assay was tested in patients with an admitting diagnosis
      of pancreatic disease at 2 tertiary care facilities. The diagnosis of acute or
      chronic pancreatitis and pancreatic cancer was determined using previously
      established criteria that incorporated symptoms, radiology, pathology, and
      serology. Plasma GP2 levels were determined in 31 patients with acute
      pancreatitis, 16 patients with chronic pancreatitis, 36 patients with pancreatic
      cancer, and 143 control subjects without pancreatic disease. Amylase and lipase
      levels were also determined in patients with acute pancreatitis. RESULTS: The GP2
      assay's sensitivity values were 0.94 for acute pancreatitis, 0.81 for chronic
      pancreatitis, and 0.58 for pancreatic cancer, which were greater than the 0.71
      for acute pancreatitis and 0.43 for chronic pancreatitis (P =.02) observed for
      amylase. The lipase assay sensitivity for acute pancreatitis was 0.66. The
      accuracy of the GP2 assay was greater than that of the amylase or lipase assays
      for acute pancreatitis (GP2 vs lipase, P =.004; GP2 vs amylase, P =.003) when
      analyzed using receiver operator characteristic curves. When daily serial blood
      samples were obtained for 13 patients with acute pancreatitis, GP2 levels
      remained abnormally elevated for at least 1 day longer than the amylase or lipase
      levels. CONCLUSION: The GP2 assay is a useful new marker for acute and chronic
      pancreatitis.

PMID- 15163233
TI  - An improved failure mode effects analysis for hospitals.
AB  - OBJECTIVE: To review the Failure Mode Effects Analysis (FMEA) process recommended
      by the Joint Commission on Accreditation of Health Organizations and to review
      alternatives. This reliability engineering tool may be unfamiliar to hospital
      personnel. DATA SOURCES: Joint Commission on Accreditation of Health
      Organizations recommendations, Mil-Std-1629A, and other articles about FMEA were
      used. STUDY SELECTION: The articles were selected by a literature search that
      included Web site-accessible material. DATA EXTRACTION: All articles found were
      used. DATA SYNTHESIS: The results are based on the articles cited and the
      author's experience in conducting FMEAs in the medical diagnostics industry.
      CONCLUSIONS: Fault trees and a list of quality system essentials are recommended
      additions to the FMEA process to help identify failure mode effects and causes.
      Neglecting mitigations for failure modes that have never occurred is a possible
      danger when too much emphasis is placed on improving risk priority numbers. A
      modified Pareto, not based on the risk priority number, is recommended when there
      are qualitatively different failure mode effects with different severities.
      Performing a FMEA that both meets accreditation requirements and reduces the risk
      of medical errors is an attainable goal, but it may require a different focus.

PMID- 15163235
TI  - Expression of cysteine protease protein 32 in prostatic adenocarcinoma correlates
      with tumor grade.
AB  - CONTEXT: Controlled cell death is mediated by apoptosis-specific genes, tumor
      suppressor genes, and oncogenes. The caspase family is a group of at least 15
      known cysteine proteases that serve as initiator and effector molecules of the
      apoptosis pathway. On activation, caspases cause cell shrinkage, condensation of
      chromatin, fragmentation of DNA, and the formation of blebs in the cytoplasmic
      membrane. OBJECTIVES: The patterns of cysteine protease protein (CCP) 32 (caspase
      3) expression have been determined in normal human tissues and a variety of
      tumors, and have been shown to correlate with the outcome in breast cancer and
      linked to resistance to chemotherapy in other tumors. This study was performed to
      determine whether CPP32 is expressed in prostatic adenocarcinoma and to define
      its relationship with outcome variables. DESIGN: Formalin-fixed, paraffin
      embedded radical prostatectomy specimens from 211 patients with prostatic
      adenocarcinoma were evaluated for CPP32 expression by immunohistochemistry.
      Hematoxylin-eosin-stained slides were reviewed, and tumors were graded based on
      the Gleason grading system. Tumors were scored for CPP32 expression
      semiquantitatively, based on the staining intensity and distribution patterns.
      These results were compared with Gleason grade and clinical and pathologic
      stages. RESULTS: One hundred thirty-three (63%) of 211 cases showed high
      expression of CPP32, whereas expression was low in 78 (37%) cases. One hundred
      three (49%) of 211 cases had a high Gleason score (7 and above). Of 103 cases
      with a high Gleason score, 74 (72%) showed high CPP32 expression. Strong
      cytoplasmic staining for CPP32 in high-grade tumors was statistically significant
      (P =.01). Also, by linear regression analysis a significant correlation was seen
      between the Gleason score and the cytoplasmic CPP32 expression (P =.001).
      Expression of CPP32 did not correlate with either clinical stage (P =.28) or
      pathologic stage (P =.60); however, this study included very few patients with
      stage IV disease. CONCLUSION: The correlation between CPP32 and high tumor grade
      suggests a CPP32-related high turnover rate in high-grade prostatic
      adenocarcinoma. Moreover, strong correlation with Gleason grade, a powerful
      predictor of disease progression and overall survival, suggests potential
      usefulness of CPP32 as a prognostic factor, especially in limited biopsy samples.

PMID- 15163236
TI  - Detection of clonality with kappa and lambda immunohistochemical analysis in
      cutaneous plasmacytomas.
AB  - CONTEXT: Cutaneous plasmacytomas rarely occur in the setting of multiple myeloma.
      However, since poorly differentiated lesions may resemble other neoplasms, such
      as carcinoma, melanoma, and lymphoma, the diagnosis of cutaneous plasmacytoma may
      be difficult. OBJECTIVE: To demonstrate clonality using kappa and lambda
      immunohistochemical analysis in cutaneous plasmacytomas and to ascertain whether
      or not interpretation is hindered by background staining. DESIGN: Pathology
      reports of all patients with the diagnosis of multiple myeloma were reviewed.
      Twelve patients had cutaneous lesions diagnosed as plasmacytoma, and these
      lesions were analyzed for light chain restriction with kappa and lambda
      immunohistochemical analysis. RESULTS: In most cases (11 of 12), monoclonality
      was demonstrated. In the remaining case, monoclonality could not be established
      because most cells did not stain for either kappa or lambda. CONCLUSIONS: Light
      chain restriction can be demonstrated in most multiple myeloma-related cutaneous
      plasmacytomas, establishing the neoplastic nature of the infiltrate.

PMID- 15163237
TI  - Fatal hemorrhagic pneumonia concomitant with Chlamydia pneumoniae and
      parainfluenza virus 4 infection.
AB  - CONTEXT: Cases of fatal hemorrhagic pneumonia need to be investigated for highly
      contagious viral causes. While not all hemorrhagic pneumonias are caused by very
      contagious agents, the etiology must be correctly determined in order to
      administer appropriate patient care. OBJECTIVE: To determine whether chlamydia,
      paramyxovirus, or mycoplasma was the causative agent in a case of fatal
      hemorrhagic pneumonia, and to evaluate the possibility that this was the first
      case of hantavirus pulmonary syndrome in Illinois. DESIGN: Nonroutine virological
      and molecular analyses were performed on lung tissue taken during an unrestricted
      autopsy of a patient who died in 2002. SETTING AND PATIENT: An elderly, male,
      Chicago-area resident with a 3-week history of nonspecific, mild upper
      respiratory tract infection was admitted for hospital treatment of the
      respiratory infection and viral myositis without cardiac involvement. The patient
      became febrile, hypoxic, developed hemorrhagic pneumonia, and died. Because he
      had proven exposure to mice and had developed hemorrhagic pneumonia, hantavirus
      pulmonary syndrome was suspected as the cause of death. Mice known to carry
      hantaviruses live in Illinois, including the Chicago area. INTERVENTIONS:
      Gatifloxacin and heparin anticoagulation were initiated because community
      acquired pneumonia and pulmonary embolism were considered likely etiologies for
      an acute exacerbation of hypoxemia. RESULTS: Two respiratory pathogens were
      isolated and identified: Chlamydia pneumoniae and human parainfluenza virus 4a.
      CONCLUSIONS: A mixed (polymicrobial) infection contributed to the patient's
      death. Hemorrhage was likely a result of anticoagulation therapy superimposed on
      lung tissues damaged by pneumonia. The uncommon nature of this case and the
      pathogens involved underscore the challenges in infection control and clinical
      evaluation that hospitals will face when confronted with possibly new and
      potentially deadly communicable diseases.

PMID- 15163238
TI  - Perivascular fibrosis in the bone marrow in sickle cell disease.
AB  - CONTEXT: Magnetic resonance imaging of bone marrow in homozygous sickle cell
      disease (hemoglobin [Hb] SS) shows nonhomogeneous, mottled signals that increase
      with age and number of crises. The pattern of these signals is reminiscent of the
      underlying vascular architecture, but histopathology of this tissue has not been
      adequately studied. OBJECTIVE: To elucidate the histopathology of blood vessels
      in the bone marrow in sickle cell disease. DESIGN: Retrospective histochemical
      morphometric study of bone marrow arteries by point counting in HbSS (13 cases)
      and sickle cell Hb C (HbSC) (8 cases) compared to nonanemic normal controls
      (HbAA) (10 cases). All patients were nondiabetic, normotensive, younger than 37
      years, and matched for age group. RESULTS: The mean point count for perivascular
      fibrous tissue was significantly greater in the HbSS group (P <.001) in both
      small (P <.001) and medium-sized (P =.002) vessels, and in both age groups
      (pediatric, P <.001; adult, P =.005) compared with the HbAA group. Additional
      analysis showed the difference was significant in HbSS pediatric small vessels (P
      <.001) and in pediatric and adult medium vessels (P =.045 and P =.03,
      respectively). Ratios of fibrous tissue to muscle showed proportionately greater
      fibrous tissue in HbSS pediatric small (P <.001) and medium-sized vessels (P
      =.02), and in adult large vessels (P =.03). Mean point counts for muscle were
      significantly decreased in HbSS small vessels when all ages were compared as a
      group (P =.02), but when compared by age groups, counts were significantly
      increased in adult HbSS medium-sized vessels (P =.01). Overall mean point counts
      for muscle and fibrous tissue in the HbSC group were intermediate between those
      of the HbSS and HbAA groups, but were not significantly different from counts in
      the HbAA group (P =.78 and P =.35, respectively). CONCLUSION: In sickle cell
      disease, arterial vessels in the bone marrow show significantly increased fibrous
      connective tissue and changes in muscle that vary with age and vessel size.

PMID- 15163239
TI  - Comparative assays for the HER-2/neu oncogene status in breast cancer.
AB  - CONTEXT: Tumor marker assays, especially those used to indicate the right
      therapy, should be standardized. OBJECTIVE: To analyze the current methods for
      the HER-2/neu (h2n) oncogene status by immunohistochemical (IHC) analysis,
      fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization
      (CISH) and compare those results with the chromosome 17 copy number and the
      status of the topoisomerase II alpha (TPIIalpha) gene. DESIGN: We tested 50
      infiltrating ductal breast carcinomas (pTNM status varied from pT1 N0 to pT4 N1)
      using the Food and Drug Administration (FDA)-approved methods HercepTest and
      Pathway for overexpression of h2n. We also used FISH and CISH to test for h2n
      amplification and CISH to test for chromosome 17 (c17) and TPIIalpha. The p53 and
      Ki-67 factors were also evaluated by IHC analysis. RESULTS: h2n overexpression
      (3+) and amplification were observed in only 6 (12%) of 50 cases by IHC analysis,
      FISH, and CISH. Three cases that initially scored 3+ and 2+ had 4 to 5.95 signals
      (equivocal) by FISH but when corrected by the h2n/c17 ratio were nonamplified.
      TPIIalpha isomerase was amplified in only 2 (4%) of the 50 cases. Nineteen (38%)
      of the 50 cases were aneuploidic. All h2n amplified cases had high proliferative
      activity, but only 2 of 6 had p53 protein alterations. CONCLUSIONS: The
      HercepTest and Pathway IHC assay h2n were fully concordant for the 3+ cases. The
      3+ cases had to be confirmed in 75% of the tumor area examined. These 2 IHC
      assays were fully concordant with FISH and CISH. The 2 in situ hybridization
      (ISH) assays were 94% concordant for the 50 cases. The cutoff signal points for
      both ISH assays should be 6 or more. Thus, there is no need for the c17 ratio
      correction. Tumor heterogeneity appears not be a major problem, but our
      percentage of amplified cases is lower than previously reported. The FDA-approved
      IHC and ISH assays should give relatively uniform results when used following our
      recommendations.

PMID- 15163240
TI  - Continuous monitoring of stat and routine outlier turnaround times: two College
      of American Pathologists Q-Tracks monitors in 291 hospitals.
AB  - CONTEXT: The laboratory test turnaround times (TATs) that exceed the expectations
      of clinicians who order those tests, the so-called outlier test reporting rates,
      may be responsible for perceptions of inadequate laboratory service. OBJECTIVE:
      To monitor outlier test reporting rates for emergency department stat potassium
      results and routine inpatient morning blood tests. DESIGN: In 2 different
      monitors, each conducted for 2 years, laboratory personnel in institutions
      enrolled in the College of American Pathologists (CAP) Q-Tracks program tracked
      the percentages of emergency department stat potassium results and/or the
      percentages of morning rounds routine test results that were reported later than
      self-imposed reporting deadlines. SETTING: A total of 291 hospitals participating
      in 2 CAP Q-Tracks monitors. RESULTS: Participants monitored 225,140 stat
      emergency department potassium TATs, of which 33,402 (14.8%) were outliers, and
      1,055040 routine morning test reporting times, of which 123,554 (11.7%) were
      outliers. For both monitors, there was a significant (P <.05) downward trend in
      the outlier rates as the number of quarters in which participants submitted data
      increased. CONCLUSION: Outlier reporting rates for emergency department stat
      potassium and routine morning test results decreased during the 2-year period of
      continuous monitoring. The CAP Q-Tracks program provides an effective vehicle by
      which providers of laboratory services may improve the timeliness with which they
      deliver the results of laboratory tests.

PMID- 15163243
TI  - Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as
      alpha(2)delta ligands at voltage-gated calcium channels.
AB  - ISSUE: Anticonvulsants that act as ligands at alpha(2)delta subunits of voltage
      gated calcium channels are proving to be novel treatments for chronic pain.

PMID- 15163244
TI  - The molecular medicine revolution and psychiatry: bridging the gap between basic
      neuroscience research and clinical psychiatry.
AB  - Recent years have witnessed a considerable increase in both fundamental knowledge
      and available experimental techniques in the basic neurosciences. Unfortunately,
      clinical translation of these findings vis-a-vis a direct benefit to patients who
      suffer from psychiatric diseases has not been as rapid. It is likely that this
      will change in the near future. We discuss some of the knowledge and expanding
      techniques of basic neuroscience, focusing on those that may be most promising
      regarding the future impact of the current molecular medicine revolution in
      psychiatry. Some of the more exciting findings (basic mechanisms, techniques, and
      clinical methodologies) that are expected to have a major impact on both our
      understanding of the biological underpinnings of psychiatric diseases and the
      development of novel and/or improved therapies include genetics, epigenetics,
      transcriptomics/proteomics, neuroimaging, animal models, and improved psychiatric
      endophenotypes.

PMID- 15163245
TI  - Using questionnaires to screen for psychiatric disorders: a comment on a study of
      screening for bipolar disorder in the community.

PMID- 15163246
TI  - How effective is St John's wort? The evidence revisited.
AB  - BACKGROUND: St. John's wort (Hypericum perforatum) has been identified as an
      effective treatment for depression in controlled studies and subsequent meta
      analyses. However, 3 recently published large studies failed to demonstrate
      robust efficacy. Updated meta-analysis and assessment of publication bias may
      help determine the true effect of St. John's wort. METHOD: Meta-analysis to
      reevaluate the effectiveness of St. John's wort as an antidepressant, funnel plot
      analysis, and meta-regression to assess the impact of publication bias, small
      study effects, and variation in trial characteristics were performed. We
      conducted 2 analyses: a reproduction of a recent meta-analysis including 15
      studies (Meta-15) and a meta-analysis extended by the 3 studies published since
      then (Meta-18). The studies in Meta-15 were identified through MEDLINE and EMBASE
      searches conducted in June 2000. The search terms used were St. John's wort,
      hypericum, hypericin, depression, and antidepressant, and no language
      restrictions were applied. For both meta-analyses, we compared funnel plots,
      Begg's rank correlation, Egger's regression, trim and fill method, and meta
      regression. RESULTS: In both analyses, effect sizes in recent studies were
      smaller than those reported in earlier studies; the addition of more recent
      studies into the analyses resulted in reduced effect size. In Meta-15, St. John's
      wort was significantly more effective than placebo with a risk ratio (RR) of 1.97
      (CI = 1.54 to 2.53). In Meta-18, the RR was reduced to 1.73 (CI = 1.40 to 2.14).
      On funnel plot analysis, the Meta-18 plot proved to be much more skewed than the
      Meta-15 plot. Meta-regression showed that increase in effect size was associated
      with smaller sample size only. The impact of baseline severity of depression
      could not be evaluated as the studies used different versions of the Hamilton
      Rating Scale for Depression. CONCLUSION: St. John's wort may be less effective in
      the treatment of depression than previously assumed and may finally be shown to
      be ineffective if future trials confirm this trend.

PMID- 15163247
TI  - What characteristics of primary anxiety disorders predict subsequent major
      depressive disorder?
AB  - OBJECTIVE: The goal of this study was to examine the associations between
      specific anxiety disorders and the risk of major depressive disorder and to
      explore the role of various clinical characteristics of anxiety disorders in
      these relationships using a prospective, longitudinal design. METHOD: The data
      are from a 4-year prospective, longitudinal community study, which included both
      baseline and follow-up survey data on 2548 adolescents and young adults aged 14
      to 24 years at baseline. DSM-IV diagnoses were made using the Munich-Composite
      International Diagnostic Interview. RESULTS: The presence at baseline of any
      anxiety disorder (odds ratio [OR] = 2.2 [95% CI = 1.6 to 3.2]) and each of the
      anxiety disorders (specific phobia, OR = 1.9 [95% CI = 1.3 to 2.8]; social
      phobia, OR = 2.9 [95% CI = 1.7 to 4.8]; agoraphobia, OR = 3.1 [95% CI = 1.4 to
      6.7]; panic disorder, OR = 3.4 [95% CI = 1.2 to 9.0]; generalized anxiety
      disorder, OR = 4.5 [95% CI = 1.9 to 10.3]) was associated with a significantly (p
      <.05) increased risk of first onset of major depressive disorder. These
      associations remained significant after we adjusted for mental disorders
      occurring prior to the onset of the anxiety disorder, with the exception of the
      panic disorder association. The following clinical characteristics of anxiety
      disorders were associated with a significantly (p <.05) increased risk of
      developing major depressive disorder: more than 1 anxiety disorder, severe
      impairment due to the anxiety disorder, and comorbid panic attacks. In the final
      model, which included all clinical characteristics, severe impairment remained
      the only clinical characteristic that was an independent predictor of the
      development of major depressive disorder (OR = 2.2 [95% CI = 1.0 to 4.4]).
      CONCLUSION: Our findings suggest that anxiety disorders are risk factors for the
      first onset of major depressive disorder. Although a number of clinical
      characteristics of anxiety disorders appear to play a role in the association
      between anxiety disorders and depression, severe impairment is the strongest
      predictor of major depressive disorder.

PMID- 15163248
TI  - Anger attacks in bipolar depression: predictors and response to citalopram added
      to mood stabilizers.
AB  - BACKGROUND: Of the 2 reports in the literature on anger attacks in bipolar
      depression, one found them to be uncommon (12%) compared with the rate in bipolar
      mixed states and unipolar depression (40%-60%), whereas the other found them to
      be common (62%). We examined anger attacks among participants in an 8-week trial
      of open-label citalopram added to mood stabilizer for the treatment of bipolar
      depression. We also examined trait anger, hypomanic symptoms, and depressive
      symptoms as predictors of anger attacks. We hypothesized that if anger attacks
      were related to hypomanic symptoms they would respond unfavorably to citalopram,
      whereas if they were related to trait anger or depressive symptoms they would
      respond favorably. METHOD: In 45 participants with a DSM-IV diagnosis of bipolar
      I or II depression, anger attacks, hypomanic symptoms, and depressive symptoms
      were assessed using a modified Anger Attacks Questionnaire, Young Mania Rating
      Scale, and Hamilton Rating Scale for Depression, respectively. Trait anger was
      measured using the State-Trait Anger Inventory. Posttreatment data were collected
      at the end of 8 weeks of treatment with citalopram or at dropout from the trial.
      The first participant study visit was in November 1998, and the final participant
      study visit was in December 2000. RESULTS: Before treatment with citalopram, 17
      (38.6%) of 44 participants reported anger attacks (data on anger attacks were
      missing for 1 participant before treatment and 4 after treatment). Significantly
      fewer participants reported anger attacks after treatment (6 of 41, 14.6%;
      McNemar test, p <.05, 2-tailed). At pretreatment and post-treatment, trait anger
      was the only significant predictor of anger attacks (p <.05). CONCLUSIONS: These
      findings suggest that in bipolar depression anger attacks are common, may respond
      favorably to acute treatment with citalopram added to mood stabilizer, and are
      better predicted by trait anger than hypomanic or depressive symptoms. Further
      studies are needed to clarify the diagnostic and treatment implications of anger
      attacks in bipolar depression.

PMID- 15163249
TI  - Are mood disorders and obesity related? A review for the mental health
      professional.
AB  - OBJECTIVE: We reviewed evidence regarding a possible relationship between mood
      disorders and obesity to better inform mental health professionals about their
      overlap. METHOD: We performed a MEDLINE search of the English-language literature
      for the years 1966-2003 using the following terms: obesity, overweight,
      abdominal, central, metabolic syndrome, depression, mania, bipolar disorder,
      binge eating, morbidity, mortality, cardiovascular, diabetes, cortisol,
      hypertriglyceridemia, sympathetic, family history, stimulant, sibutramine,
      antiobesity, antidepressant, topiramate, and zonisamide. We evaluated studies of
      obesity (and related conditions) in persons with mood disorders and of mood
      disorders in persons with obesity. We also compared studies of obesity and mood
      disorders regarding phenomenology, comorbidity, family history, biology, and
      pharmacologic treatment response. RESULTS: The most rigorous clinical studies
      suggest that (1). children and adolescents with major depressive disorder may be
      at increased risk for developing overweight; (2). patients with bipolar disorder
      may have elevated rates of overweight, obesity, and abdominal obesity; and (3).
      obese persons seeking weight-loss treatment may have elevated rates of depressive
      and bipolar disorders. The most rigorous community studies suggest that (1).
      depression with atypical symptoms in females is significantly more likely to be
      associated with overweight than depression with typical symptoms; (2). obesity is
      associated with major depressive disorder in females; and (3). abdominal obesity
      may be associated with depressive symptoms in females and males; but (4). most
      overweight and obese persons in the community do not have mood disorders. Studies
      of phenomenology, comorbidity, family history, biology, and pharmacologic
      treatment response of mood disorders and obesity show that both conditions share
      many similarities along all of these indices. CONCLUSION: Although the overlap
      between mood disorders and obesity may be coincidental, it suggests the two
      conditions may be related. Clinical and theoretical implications of this overlap
      are discussed, and further research is called for.

PMID- 15163250
TI  - A novel, point-of-care test for lithium levels: description and reliability.
AB  - BACKGROUND: Lithium is a highly effective agent for numerous psychiatric
      disorders but requires therapeutic monitoring because of its narrow therapeutic
      index. This article describes a novel instant blood test that will facilitate the
      routine monitoring process. METHOD: This instant blood test allows the clinician
      to take a finger-stick sample of whole blood and determine the plasma lithium
      level in a 2-minute period. This new test is compared with standard laboratory
      measurements for lithium in human subjects. The reliability of the new test is
      reported as agreement with standard laboratory values in 3 studies involving a
      total of 269 subjects. RESULTS: The test demonstrates extremely high reliability
      (r = 0.962, 0.928, 0.983 for studies 1-3, respectively) for the measurement of
      serum and plasma lithium levels as compared with standard laboratory measures.
      CONCLUSION: This new test is reliable and offers unique advantages over standard
      laboratory procedures for measuring lithium levels in patients.

PMID- 15163252
TI  - Risperidone in the treatment of delirium: results from a prospective open-label
      trial.
AB  - BACKGROUND: Effective treatment is necessary to reverse delirium and prevent
      potentially serious consequences. METHOD: Patients were identified for screening
      by initial chart review of all consecutive admissions to the general medical or
      surgical wards at the Department of Veterans Affairs hospital and the University
      of Mississippi Medical Center in Jackson, Mississippi, between November 2000 and
      April 2002. Medically ill patients with delirium defined by DSM-IV criteria and a
      Delirium Rating Scale (DRS) score of >or= 13 were given risperidone, 0.5 mg,
      twice daily, with additional doses permitted on day 1 for target symptoms. Total
      day 1 dosage was given daily until the DRS score was <or= 12; dosage was then
      decreased by 50% (maintenance dose) and continued until day 6. Daily assessment
      included DRS, Cognitive Test for Delirium (CTD), and modified Extrapy-ramidal
      Symptom Rating Scale. Functional status (Karnofsky Scale of Performance Status;
      KSPS) and medical burden (Cumulative Illness Rating Scale) were assessed at
      baseline and day 6. RESULTS: Ten patients (mean age = 64.7 years) were enrolled.
      Mean daily maintenance risperidone dosage was 0.75 mg. Mean CTD scores improved
      from day 1 to the day maintenance dose was initiated (p <.0005) and remained
      improved at day 6 (7.1 +/- 2.0 and 16.9 +/- 3.0, days 1 and 6, respectively; p
      =.0078). Mean DRS scores improved from day 1 to the day maintenance dose was
      initiated (p <.0001) and remained improved at day 6 (25.2 +/- 0.9 and 11.3 +/-
      1.5, days 1 and 6, respectively; p <.0001). Mean KSPS scores improved from 32.0
      on day 1 to 45.5 on day 6 (p =.044). No patient developed movement disorders. One
      patient each discontinued because of sedation and hypotension. CONCLUSION: Low
      dose risperidone can improve cognitive and behavioral symptoms of delirium in
      medically ill patients.

PMID- 15163253
TI  - A 6-month, multicenter, open-label evaluation of beaded, extended-release
      carbamazepine capsule monotherapy in bipolar disorder patients with manic or
      mixed episodes.
AB  - BACKGROUND: Carbamazepine is frequently used for treating bipolar disorder, but
      few large trials have assessed its efficacy in preventing relapse. We evaluated
      open-label monotherapy with beaded extended-release carbamazepine capsules (ERC
      CBZ; SPD417) as continuation and short-term maintenance therapy in bipolar
      disorder patients with manic and mixed episodes. METHOD: A 6-month, open-label
      study enrolled 92 patients with DSM-IV bipolar disorder (most recent episode: 67%
      [N = 62] mixed, 33% [N = 30] manic) who had participated in 2 previous 3-week,
      double-blind, placebo-controlled studies. Subjects received beaded ERC-CBZ (200
      1600 mg/day), titrated at investigators' discretion to a final mean dose of 938
      mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary
      efficacy measure was time to relapse, and secondary efficacy measures included
      Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and
      Hamilton Rating Scale for Depression (HAM-D) scores. Data were gathered from
      January 2000 to January 2002. RESULTS: Of 77 patients analyzed in the intent-to
      treat population, 11 (14.3%) relapsed. Fifty-three patients (68.8%) discontinued
      early, including 18 (23.4%) due to adverse events. Observed mean time to relapse
      was 61.1 days, while estimated mean time to relapse based on the Kaplan-Meier
      model was 141.8 days. Improvements on the YMRS, CGI, and HAM-D from the beginning
      of prior double-blind treatment were maintained. The most common adverse events
      were headache, dizziness, and rash. No significant weight gain was noted.
      CONCLUSION: We noted a low relapse rate with beaded ERC-CBZ in this 6-month
      trial. Adverse events were generally mild to moderate and were typical of those
      associated with carbamazepine. Controlled studies are warranted to further
      explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder.

PMID- 15163251
TI  - Frontal cerebral perfusion after antidepressant drug treatment versus ECT in
      elderly patients with major depression: a 12-month follow-up control study.
AB  - BACKGROUND: Little is known about the evolution of brain perfusion alterations in
      patients with major depression, and still less about the changes in functional
      neuroimage produced by different antidepressant biological treatments. METHOD:
      Between January 2001 and December 2003, long-term follow-up frontal brain
      perfusion was compared in 2 subgroups of elderly patients (>or= 60 years) treated
      for severe unipolar major depression (DSM-IV): one subgroup of 16 patients
      administered electroconvulsive therapy, and another of 26 patients receiving
      pharmacologic treatment. All patients were remitters. A medication-free brain
      single photon emission computed tomography was performed in baseline conditions
      and after a minimum period of 12 months of euthymia. Twenty-eight age- and sex
      matched healthy controls were also assessed. RESULTS: No significant differences
      were found between the 2 subgroups in frontal uptake ratios after a 12-month
      follow-up period of euthymia. During the acute episode, patients presented
      significant anterior hypofrontality; 12 months later the hypofrontality had
      disappeared. CONCLUSION: The long-term evolution of frontal perfusion in elderly
      major depressives who respond to antidepressant biological treatment is
      essentially the same in those who receive electroconvulsive therapy and in those
      who receive medication.

PMID- 15163254
TI  - Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus.
AB  - BACKGROUND: Several studies have indicated that type 2 diabetes mellitus is more
      common among schizophrenic patients than in the general population. In this
      study, we investigated whether the use of antipsychotic drugs in patients with
      diabetes leads to worsening of glycemic control. METHOD: In this cohort study,
      patients with newly diagnosed type 2 diabetes were selected from the PHARMO
      Record Linkage System, which comprises pharmacy records for all 320000 residents
      of 6 Dutch cities. In total, we identified 2585 patients with incident cases of
      type 2 diabetes who began treatment with oral hypoglycemic agents between 1991
      and 1997 and had a medication history of at least 2 years after diagnosis of
      diabetes. A change in treatment from oral hypoglycemic agents alone to insulin
      therapy (with or without continuation of oral hypoglycemic agents) was considered
      a proxy for deterioration of beta-cell function. We compared the incidence of
      initiation of insulin therapy between users and nonusers of antipsychotic drugs
      by performing a Cox proportional hazards model analysis. RESULTS: We found an
      increased risk for initiation of insulin therapy at 2 years after diagnosis of
      diabetes in users of antipsychotics compared with nonusers; the relative hazard
      (hazard ratio) was 2.0 (95% CI = 1.2 to 3.3), which did not change after
      adjustment for potential confounders. The risk decreased in the years after
      diagnosis of diabetes. CONCLUSION: It seems that use of antipsychotics by
      patients with type 2 diabetes mellitus is associated with initiation of insulin
      therapy (i.e., "secondary failure"), especially in the first 2 years of the
      disease.

PMID- 15163255
TI  - Patterns of concomitant psychotropic medication use during a 2-year study
      comparing clozapine and olanzapine for the prevention of suicidal behavior.
AB  - BACKGROUND: Results from the International Suicide Prevention Trial (InterSePT)
      indicate that clozapine is more effective than olanzapine in reducing suicidal
      behavior in schizophrenic and schizoaffective patients. However, because
      InterSePT allowed the uncontrolled use of concomitant psychotropic medications
      (CPMs), it is possible that the antisuicidal effect of clozapine may have been
      influenced by greater use of such agents. This article describes the use patterns
      of CPMs during InterSePT and examines whether CPM use may have affected study
      outcome. METHOD: In this study, 479 patients received clozapine and 477 patients
      received olanzapine. Concomitant psychotropic medications were grouped into 4
      classes: antipsychotics, antidepressants, sedatives/anxiolytics, and mood
      stabilizers. The doses of each CPM were converted into dosage equivalents of
      standard reference drugs. An analysis of covariance was performed to compare mean
      daily doses of CPMs between the 2 groups over the 2-year treatment period. The
      duration of treatment for each patient was 2 years, with the first patient
      entering the study in March 1998 and the last patient completing treatment in
      February 2001. RESULTS: Approximately 90% of patients in both treatment groups
      received at least 1 CPM. The mean +/- SD number of CPMs per patient was 3.8 +/-
      2.90 in the clozapine group and 4.2 +/- 3.16 in the olanzapine group. For each
      CPM class, the mean daily dose was statistically significantly lower in the
      clozapine group (antipsychotics, p <.001; antidepressants, p <.01;
      sedatives/anxiolytics, p <.001; mood stabilizers, p <.05). Analyses of CPM use by
      study intervals, suicide attempters versus nonattempters, study completers versus
      noncompleters, and geographic region resulted in similar findings. CONCLUSION:
      The results support the conclusion that the effects of clozapine in reducing the
      risk of suicidal behavior derive from its intrinsic pharmacology and not from the
      influence of concomitant psychotropic medications.

PMID- 15163257
TI  - A history of major depressive disorder influences intent to die in violent
      suicide attempters.
AB  - BACKGROUND: The inconsistency of the results obtained in biological studies of
      suicidal behavior may be due to the use of broad categories lacking validity. In
      previous genetic studies, in which we identified an association between a
      serotonin-related gene and violent suicide attempts, we suggested that a history
      of major depressive disorder (MDD) might influence this association. In this
      study, we aimed to clarify the relationships between the violence of suicide
      attempts, intent to die, and depression in a large sample of suicide attempters.
      METHOD: We investigated intent to die, according to history of violent suicide
      attempts and MDD, in 502 consecutively admitted suicide attempters. We
      characterized patients in terms of lifetime DSM-IV Axis I diagnoses, suicidal
      intent (Beck Suicide Intent Scale), and history of violent suicide attempts.
      RESULTS: Suicidal intent, for both the last suicide attempt before admission and
      the most lethal suicide attempt, was higher in those with history of MDD (p =.03
      and p =.04, respectively) but was not affected by history of violent suicide
      attempt. In violent suicide attempters, suicidal intent was higher in patients
      with a history of MDD than in patients with no such history (p =.04 for last
      suicide attempt and p =.02 for most lethal attempt), whereas MDD had no effect on
      suicidal intent in nonviolent suicide attempters. CONCLUSION: Violent suicide
      attempters constitute a heterogeneous group in terms of suicidal intent. Our
      results suggest that biological and genetic studies should take into account the
      method used to attempt suicide, intent to die, and history of MDD.

PMID- 15163256
TI  - Clozapine and hypertension: a chart review of 82 patients.
AB  - OBJECTIVE: Clozapine has been linked to significant weight gain and increase in
      serum lipids and appears to negatively impact glucose metabolism. In this
      retrospective chart review study, we examine changes in systolic and diastolic
      blood pressure and treatment for hypertension in clozapine-treated patients.
      METHOD: Data on demographics and systolic and diastolic blood pressure were
      examined for up to 5 years (September 1987 to September 1992) in 82 patients
      treated with clozapine. Rates of hypertension treatment in clozapine-treated
      patients were compared with patients receiving conventional antipsychotics (N =
      56) and other atypical antipsychotic agents (N = 102). RESULTS: The mean age of
      the 82 patients at the time of clozapine initiation was 36.4 +/- 7.8 years, with
      22 (27%) female, 75 (91%) white, 3 (4%) black, 3 (4%) Hispanic, and 1 (1%) Asian.
      The baseline weight was 175.5 +/- 34.0 lb (79.0 +/- 15.3 kg) and baseline body
      mass index was 26.9 +/- 5.0 kg/m(2). There was a significant increase in systolic
      blood pressure (p =.0004) and diastolic blood pressure (p =.0001). Overall, 22
      patients (27%) received treatment for hypertension following clozapine
      initiation. Only 2 (4%) of 56 patients in the conventional antipsychotic group
      and 9 (9%) of 102 patients in the other atypical antipsychotic group (olanzapine,
      N = 6; risperidone, N = 3) received treatment for hypertension. CONCLUSION: Our
      findings suggest that long-term clozapine treatment is associated with increased
      rates of hypertension, which may have a significant impact on medical morbidity
      and mortality.

PMID- 15163259
TI  - Prevalence of diabetes mellitus among outpatients with severe mental disorders
      receiving atypical antipsychotic drugs.
AB  - BACKGROUND: Recent studies have suggested that patients receiving atypical
      antipsychotic drugs are at increased risk for developing diabetes mellitus. The
      purpose of this study is to examine the prevalence of diabetes in a group of
      adults with schizophrenia and other severe mental disorders receiving atypical
      antipsychotic drugs within a community mental health center setting. METHOD: A
      retrospective chart review was conducted on 436 outpatients receiving either
      atypical antipsychotic or decanoate antipsychotic drugs at a community mental
      health center. Diagnosis of diabetes was established through the presence of
      documentation in the medical record. Patients with a history of diabetes prior to
      age 18 years were excluded. Data were gathered from April 2001 through September
      2002. RESULTS: The mean (SD) age of patients was 42.5 (10.8) years, and 57.3%
      were men. Patients were 61.5% white, 31.8% black, 5.3% Hispanic, and 2.3% other.
      Seventeen percent of patients had a positive family history of diabetes. Point
      prevalence of diabetes was 14.2% for the entire group. Chi-square analysis for
      the group revealed significant effects of age (chi(2) = 16.514, p <.001), family
      history of diabetes (chi(2) = 27.128, p <.001), and gender (chi(2) = 14.114, p
      <.001). A trend was noted toward a higher prevalence of diabetes among patients
      receiving atypical drugs (15.2%) compared with those receiving decanoate drugs
      (6.3%) (chi(2) = 2.984, p =.078). CONCLUSION: Prevalence of diabetes mellitus
      among outpatients with severe mental disorders receiving atypical antipsychotic
      drugs is substantially higher than that reported in the general population.
      Results of this study are limited by the retrospective methodology, which may
      underestimate actual prevalence by failing to detect undiagnosed cases.

PMID- 15163258
TI  - A single-blind, randomized trial comparing quetiapine and haloperidol in the
      treatment of tardive dyskinesia.
AB  - BACKGROUND: While the atypical antipsychotics should ultimately reduce the
      prevalence of tardive dyskinesia, it is likely to remain a significant clinical
      problem for a long time to come. No strategy has clearly emerged as the treatment
      of choice for tardive dyskinesia. Atypical antipsychotics have reduced
      propensities for producing acute extrapyramidal symptoms (EPS) and possibly
      tardive dyskinesia and may be effective in treating patients with established
      tardive dyskinesia. METHOD: This 12-month, randomized, investigator-blinded study
      compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating
      patients with DSM-IV schizophrenia or schizoaffective disorder and established
      tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom
      Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression
      (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and
      glycosylated hemoglobin level were also assessed. Subjects were enrolled in the
      study between April 2000 and March 2002. RESULTS: Mean endpoint doses were 400
      mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol
      group, the quetiapine group showed significantly greater improvements in ESRS
      dyskinesia (6 and 9 months [p <or=.01]) and CGI dyskinesia (from 6 months onward
      [p <.05] and with repeated-measures analysis [p =.002]). Response rate (>or= 50%
      symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and
      37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS
      decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p
      =.002) months. Serum prolactin levels decreased with quetiapine but increased
      with haloperidol, differing significantly between the groups at endpoint (p
      =.005). No significant changes in weight or glucose metabolism were recorded in
      either group. CONCLUSION: Quetiapine effectively reduces the severity of tardive
      dyskinesia and is well tolerated in patients with established tardive dyskinesia.

PMID- 15163260
TI  - Risperidone in combination with mood stabilizers: a 10-week continuation phase
      study in bipolar I disorder.
AB  - BACKGROUND: Combination therapy (risperidone and a mood stabilizer) for patients
      with a history of bipolar disorder (DSM-IV) and hospitalized for treatment of a
      manic episode was assessed in a 13-week study. METHOD: Subjects received flexible
      doses of a mood stabilizer (lithium or divalproex) plus placebo, risperidone, or
      haloperidol in a 3-week double-blind study. They could then enter a 10-week open
      label study during which they received risperidone combined with a mood
      stabilizer. RESULTS: Of the 156 patients enrolled in the 3-week study, 85 entered
      the 10-week open-label extension, of whom 48 completed 10 weeks of treatment. The
      mean +/- SE doses of risperidone were 3.8 +/- 0.3 mg/day during the 3-week study
      and 3.1 +/- 0.2 mg/day during the 10-week study. At double-blind endpoint, mean
      reductions in Young Mania Rating Scale (YMRS) scores were significantly greater
      in patients receiving risperidone plus mood stabilizer than in those receiving
      placebo plus mood stabilizer (-14.3 vs. -8.2, p <.001). Further significant (p
      <.001) reductions were seen during the 10 weeks of treatment with risperidone
      plus mood stabilizer. Symptom remission (YMRS score <or= 12) was seen in 38
      patients (79%) at the end of the 10-week study. Scores on the Brief Psychiatric
      Rating Scale, Hamilton Rating Scale for Depression, and Clinical Global
      Impressions scale improved significantly (p <.05) during both the 3-week and 10
      week studies. Treatment was well tolerated, and modest weight gain was observed
      during the 13-week study period. CONCLUSION: The combination of risperidone and a
      mood stabilizer was efficacious and well tolerated in the continuation treatment
      of patients initially hospitalized for the management of an acute manic episode.

PMID- 15163261
TI  - Cardiovascular disease in patients with schizophrenia in Saskatchewan, Canada.
AB  - BACKGROUND: Studies have shown that patients with schizophrenia have higher rates
      of cardiovascular disease and mortality compared with the general population.
      However, population-based data on the prevalence, incidence, and mortality of
      cardiovascular disease are needed. METHOD: In this retrospective cohort study,
      the Saskatchewan Health databases were searched for all patients diagnosed with
      schizophrenia (ICD-9 code 295) in 1994 or 1995. 3022 subjects were identified.
      For each subject, 4 age- and sex-matched comparison individuals were selected
      randomly among residents of the province who had no diagnosis of schizophrenia or
      any other mental disorders and who received no prescriptions for antipsychotic
      medications. Prevalence of cardiovascular morbidity during 1994 and 1995 and
      incidence of cardiovascular morbidity and mortality during the follow-up period
      of January 1996 through March 1999 were analyzed. RESULTS: Concerning prevalence
      of morbidity in schizophrenia patients, significantly increased risk-adjusted
      odds ratios were as follows: arrhythmia, 1.5 (95% CI = 1.2 to 1.8); syncope, 4.0
      (95% CI = 2.0 to 7.9); heart failure, 1.7 (95% CI = 1.4 to 2.2); stroke, 2.1 (95%
      CI = 1.6 to 2.7); transient cerebral ischemia, 2.6 (95% CI = 1.7 to 3.7); and
      diabetes, 2.1 (95% CI = 1.8 to 2.4). Odds of acute myocardial infarction,
      ischemic heart disease, and ventricular arrhythmias were not significantly
      different from those for the comparison group. Concerning incidence of morbidity
      and mortality in the patients, adjusted relative risk was significantly increased
      for ventricular arrhythmia, 2.3 (95% CI = 1.2 to 4.3); heart failure, 1.6 (95% CI
      = 1.2 to 2.0); stroke, 1.5 (95% CI = 1.2 to 2.0); diabetes, 1.8 (95% CI = 1.2 to
      2.6); all-cause mortality, 2.8 (95% CI = 2.3 to 3.4); and cardiovascular
      mortality, 2.2 (95% CI = 1.7 to 2.8). CONCLUSIONS: Persons with schizophrenia
      appear to be at greater risk for cardiovascular morbidity and mortality than
      those in the general population.

PMID- 15163262
TI  - Financial support for letter writing.

PMID- 15163264
TI  - Schizophrenia as a manifestation of X-linked Mcleod-Neuroacanthocytosis syndrome.

PMID- 15163265
TI  - Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction
      in a patient taking risperidone and lithium carbonate.

PMID- 15163266
TI  - Dosing differences between valproic acid concentrate and divalproex sodium: a
      case report.

PMID- 15163267
TI  - A case of kleptomania correlating with premenstrual dysphoria.

PMID- 15163268
TI  - Acetaminophen preferable to ibuprofen for pretreatment of electroconvulsive
      therapy-induced headache.

PMID- 15163269
TI  - Chemotherapeutic management of malignant pleural effusion.
AB  - The management of malignant pleural effusions are a common, and sometimes
      difficult, therapeutic problem. This article reviews the currently available
      sclerosing agents and discusses novel agents that show promise for the future.
      Talc, tetracycline and bleomycin are currently the most widely used agents but
      none is an ideal sclerosant and certain adverse effects are of concern. Novel
      agents, particularly transforming growth factor (TGF)-beta(2) and
      metalloproteinase inhibitors, are being investigated, and the increase in
      knowledge into the mechanisms of pleural fluid formation and pleurodesis will
      hopefully lead to the development of targeted therapy in the future.

PMID- 15163270
TI  - Delaying surgery with chemotherapy for osteosarcoma of the extremities.
AB  - Osteosarcoma is the most frequent primary cancer of bone. When treated by surgery
      alone, it is almost invariably followed by metastatic dissemination and death.
      This dismal prognosis can be improved dramatically by including chemotherapy in
      an interdisciplinary regimen. Today, two-thirds of patients with localised
      extremity primaries can achieve long-term survival with such intensive multimodal
      therapy. This article provides a summary overview of current pharmacotherapy in
      osteosarcoma of the extremities, focussing on the approach of preoperative
      'neoadjuvant' chemotherapy and thus, the potential benefits and pitfalls of
      delaying surgery. Prospective, multi-institutional trials are essential in
      guaranteeing that as many patients as possible can benefit from modern,
      efficacious interdisciplinary therapeutic regimens and that further progress can
      be made.

PMID- 15163272
TI  - Gallbladder cancer: current status.
AB  - Gallbladder cancer (GBC) is the most common biliary tract malignancy. There is a
      tremendous regional variability in its incidence. Risk factors include genetic
      susceptibility, gender, presence of gallstones, chronic biliary infections, diet
      and some anatomical anomalies. Several genetic abnormalities have been described
      which may be aetiologically important as well as carry prognostic significance.
      These include mutations in the proteins K-RAS and P53, and altered expression of
      P-glycoprotein, COX-2 and epidermal growth factor receptor. Most patients present
      at an advanced stage, overall prognosis is very poor. TNM stage and the extent of
      surgical resection are the most important prognostic factors. Surgery is the only
      curative therapy reserved for patients with early-stage disease. The role of
      adjuvant therapy is not fully defined. Patients with advanced disease are managed
      with systemic chemotherapy that is primarily palliative. Although 5-fluorouracil
      alone, or in combination, has been most commonly utilised, there is much greater
      enthusiasm for the combination of cisplatin and gemcitabine. The availability of
      better drugs and combinations may affect the use of chemotherapy in neoadjuvant
      and adjuvant settings. Novel targeted therapies require exploration alone or in
      combination with chemotherapy.

PMID- 15163271
TI  - Pharmacological management of Ewing sarcoma family of tumours.
AB  - The Ewing sarcoma family of tumours comprises of a group of well-characterised
      neoplasms with aggressive behaviour. Despite significant progress with the use of
      intensive multiagent chemotherapy and local control measures, a significant
      proportion of patients die because of disease progression. Most treatment
      regimens are based on the intensification of alkylating agents and topoisomerase
      II inhibitors. Using this approach, the expected survival rate is between 70 and
      80% in patients with localised disease. An increasingly important complication
      among survivors is the development of treatment-related haematological
      malignancies. The outcome for patients with metastatic disease is very poor and
      many studies have explored the use of high-dose chemotherapy with haematopoietic
      stem cell transplantation (HSCT). The benefit of this approach is unclear and
      HSCT must therefore be considered investigational. New strategies, such as the
      use of immunotherapy, biological modifiers and novel classes of chemotherapeutic
      agents must be explored.

PMID- 15163274
TI  - Management of pituitary apoplexy.
AB  - Pituitary apoplexy is a rare clinical syndrome caused by sudden haemorrhaging or
      infarction of the pituitary gland, generally within a pituitary adenoma. Headache
      of sudden and severe onset is the main symptom, associated with visual
      disturbances or ocular palsy. Signs of meningeal irritation or altered
      consciousness may complicate the diagnosis. Corticotropic deficiency (secondary
      adrenal failure) may be life-threatening if untreated. Computed tomography (CT)
      or magnetic resonance imaging (MRI) confirm the diagnosis by revealing a
      pituitary tumour with haemorrhagic and/or necrotic components: CT is most useful
      in the acute setting (24 - 48 h), MRI is useful for identifying blood components
      in the subacute setting (4 days to 1 month). Owing to the highly variable course
      of this syndrome and the limited individual experience, the optimal management of
      acute pituitary apoplexy is controversial. Some authors advocate early
      transphenoidal surgical decompression for all patients, whereas others adopt a
      more conservative approach for selected patients (those without visual acuity or
      field defects and with normal consciousness). Glucocorticoid treatment must
      always be initiated immediately, at a dose of hydrocortisone 50 mg every 6 h.

PMID- 15163273
TI  - The role of alpha-blockers in the management of prostate cancer.
AB  - Prostate cancer is the second most common cause of cancer death in men in the US.
      Patients with prostate cancer are initially treated with surgical resection,
      radiation or antiandrogen therapy. After an initial remission, however, the
      majority of prostate tumours evolve into a highly aggressive, metastatic androgen
      independent state, for which successful therapy has not yet been established.
      During the past few years, new perspectives have emerged towards the development
      of preventive and therapeutic approaches for prostate cancer. Quinazoline-based
      alpha(1)-blockers have been shown to have antitumour efficacy against prostate
      cancer cells in inducing apoptosis and anoikis via an alpha(1)-adrenoceptor
      independent mechanism. Specifically, doxazosin and terazosin can induce
      apoptosis, inhibit invasion and migration of prostate cancer and endothelial
      cells, and reduce their adhesion potential to extracellular matrix components,
      thus enhancing their susceptibility to anoikis. This review discusses recent
      evidence suggesting the apoptotic efficacy of quinazoline-based alpha(1)
      adrenoceptor antagonists, doxazosin and terazosin and speculates on the
      therapeutic promise of these drugs as novel antitumour agents against prostate
      cancer. From a drug discovery perspective, separation of the effect of doxazosin
      on apoptosis in prostate cancer cells from its original pharmacological activity
      in normal prostate cells, will provide a molecular basis in developing a novel
      class of apoptosis-inducing agents through lead optimisation.

PMID- 15163275
TI  - Pharmacological strategies in relieving neuropathic pain.
AB  - The pharmacological treatment of neuropathic pain relies, to a large extent, on
      drugs belonging to a small number of defined classes. Opioids, tricyclic
      antidepressants, antiepileptic drugs and membrane stabilisers form the current
      basis of treatment. Varying levels of evidence support the use of individual
      members of these classes and overall show no indication that one class of drug,
      or individual drug has universal effectiveness. More refined knowledge of the
      modes of action of these agents used to treat neuropathic pain should lead to a
      more logical approach to the management of this difficult series of conditions. A
      number of drugs currently licensed for a different indication have recently had
      an analgesic effect in neuropathic pain attributed to them. In addition, a number
      of novel compounds are undergoing investigation and provide hope of dicovering
      more efficacious treatment options in the future.

PMID- 15163276
TI  - Pharmacological management of attention-deficit hyperactivity disorder.
AB  - Pharmacotherapy is the most common intervention for attention-deficit
      hyperactivity disorder (ADHD). Stimulant medications are highly efficacious and
      are the gold-standard for treating the inattention, impulsivity and excessive
      motoric activity associated with ADHD. Methylphenidate and amphetamine-based
      stimulants are now available in longer-acting, once-daily and shorter-acting
      divided dosing schedules. Several nonstimulant, second-line treatments are now
      available or under development for the treatment of ADHD in children and adults.
      This article reviews the support for a variety of pharmacological agents and the
      issues to be considered when selecting an agent. The authors conclude that there
      is a need for additional direct comparisons between the longer-acting agents to
      effectively guide the practicing clinician.

PMID- 15163278
TI  - Review of the immunosuppressant enteric-coated mycophenolate sodium.
AB  - Enteric-coated mycophenolate sodium (EC-MPS; myfortic, Novartis Pharma AG) is an
      advanced formulation delivering mycophenolic acid (MPA). EC-MPS was designed to
      improve MPA-related upper gastrointestinal adverse events by delaying the release
      of MPA until reaching the small intestine. At a dose of 720 mg, EC-MPS exhibits
      equivalent MPA exposure (area under the concentration curve [AUC]) and maximal
      MPA concentration (C(max)) to mycophenolate mofetil (MMF; CellCept, Roche AG)
      1000 mg. The time to maximal MPA concentration (T(max)) for EC-MPS is delayed
      relative to that for MMF, consistent with a functioning enteric coating. EC-MPS
      720 mg b.i.d. has demonstrated therapeutic equivalence to MMF 1000 mg b.i.d. in
      renal transplant patients. Recent clinical trials have demonstrated that EC-MPS
      is as effective and safe as MMF in both de novo and maintenance renal transplant
      patients. Furthermore, studies have confirmed that maintenance patients can be
      safely converted from MMF to EC-MPS with no compromise of efficacy or safety. EC
      MPS therefore presents physicians and patients with a valid alternative MPA
      therapy with a comparable efficacy and safety profile to MMF.

PMID- 15163279
TI  - Aceclofenac in the management of inflammatory pain.
AB  - Aceclofenac (Almirall Prodesfarma SA) is an oral NSAID that is effective in the
      treatment of painful inflammatory diseases and has been used to treat > 75
      million patients worldwide. It has proved as effective as diclofenac, naproxen
      and piroxicam in patients with osteoarthritis, diclofenac, ketorolac, tenoxicam
      and indomethacin in patients with rheumatoid arthritis and tenoxicam, naproxen
      and indomethacin in patients with ankylosing spondylitis. It also provides
      effective analgesia in other indications, such as dental or gynaecological pain,
      lower back pain and ear, nose and throat indications. Aceclofenac appears to be
      particularly well-tolerated amongst the NSAIDs, with a lower incidence of
      gastrointestinal adverse effects. This good tolerability profile results in a
      reduced withdrawal rate and hence greater compliance with treatment.

PMID- 15163277
TI  - A review of the proteasome inhibitor bortezomib in multiple myeloma.
AB  - Multiple myeloma (MM) represented 14% of new haematological malignancies in the
      US in 2003 and almost 19% of anticipated deaths. Treatment with standard
      chemotherapy has resulted in a median survival of about 3 years and despite the
      improvements in survival seen with the use of intensive therapy supported by
      autologous stem cell transplantation, MM remains incurable; hence, new
      therapeutic strategies are urgently needed. One novel approach to the treatment
      of MM is the use of proteasome inhibitors. Proteasomes are ubiquitous protease
      complexes involved in diverse aspects of cell biology, such as protein
      homeostasis, cell cycle progression, apoptosis and inflammation, as well as
      resistance to antineoplastic therapy. The first-in-class proteasome inhibitor,
      bortezomib was recently approved in the US for the treatment of patients with MM
      who have received at least two prior therapies and are progressing on their last
      therapy. Its use in earlier-stage MM, other haematological malignancies and in
      solid tumours as monotherapy and in combination therapy is currently under
      investigation.

PMID- 15163280
TI  - Long-term oral carvedilol in chronic heart failure.
AB  - The long-term beta-blockade strategy with carvedilol, metoprolol succinate or
      bisoprolol is now strongly recommended to reduce the rates of mortality and
      morbidity in patients with chronic heart failure (CHF). Although the benefits
      observed with such drugs are viewed as a class effect, theoretically, carvedilol
      might be superior to the other two agents, considering its unique pharmacological
      profile, which includes a more comprehensive antiadrenergic activity and
      potentially relevant ancillary properties. So far, carvedilol has been proven to
      be effective and safe in a broader range of CHF patients than metoprolol and
      bisoprolol. Moreover, a recent large clinical trial has shown a significantly
      greater survival benefit with carvedilol as directly compared with metoprolol
      tartrate. Therefore, carvedilol may be the preferred beta-blocking agent to treat
      patients with CHF.

PMID- 15163281
TI  - Fondaparinux: a Factor Xa inhibitor for antithrombotic therapy.
AB  - Fondaparinux (Arixtra) is the first of a new class of antithrombotic compounds -
      Factor Xa inhibitors. This synthetic pentasaccharide acts by inhibiting Factor Xa
      selectively. Its efficacy and safety have been demonstrated in animal models of
      venous and arterial thromboses and bleeding risk. In humans, its pharmacokinetic
      profile after subcutaneous injection shows a rapid onset of antithrombotic
      activity and an elimination half-life that reliably allows once-daily dosing. As
      the inter-subject variability is limited, no laboratory monitoring of coagulation
      parameters is needed. The efficacy and safety of fondaparinux have been examined
      in several Phase II and III clinical trials. So far, the largest programme has
      involved approximately 9000 patients undergoing major orthopaedic surgery of the
      lower limbs. In the setting of short-term prophylaxis, the efficacy of
      fondaparinux for preventing venous thromboembolism was significantly superior to
      that of the low-molecular-weight heparin, enoxaparin (common reduction in risk:
      50.6%; p < 0.001). The benefit of extended thromboprophylaxis with fondaparinux
      in hip fracture surgery patients was also demonstrated. Fondaparinux also showed
      benefit in the prevention of venous thromboembolism in other surgical and medical
      settings and in the treatment of patients with venous thromboembolism. Overall,
      fondaparinux therapy was as well-tolerated as currently available treatments. In
      conclusion, selective inhibition of Factor Xa is an effective antithrombotic
      strategy. Fondaparinux may substantially improve the prevention and treatment of
      thrombosis. Fondaparinux 2.5 mg once-daily s.c. has been approved for the
      prevention of venous thromboembolism after major orthopaedic surgery.
      Fondaparinux use in extended prophylaxis (4 weeks) after hip fracture surgery has
      also been recently approved.

PMID- 15163282
TI  - Extended-release niacin for modifying the lipoprotein profile.
AB  - Niacin (nicotinic acid) favourably modifies all aspects of the lipoprotein
      profile; it raises high-density lipoprotein cholesterol (HDL-C) levels, lowers
      triglyceride, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a)
      levels and reduces atherogenic small, dense LDL particles. One large monotherapy
      trial and multiple trials of niacin in combination with other lipid-modifying
      drugs show remarkable consistency in the ability of niacin to improve
      angiographic and clinical outcomes. In practice, however, the use of regular,
      immediate-release niacin (niacin IR) has been limited by the side effect of
      flushing. Sustained-release (SR) formulations, developed in order to reduce
      flushing, were found to cause serious hepatotoxicity at varying frequencies.
      Extended-release niacin (niacin ER; Niaspan), Kos Pharmaceuticals, Inc.) is a
      prescription formulation of niacin, administered once-daily at bedtime. Niacin ER
      is as effective in modifying lipoprotein levels as an equal daily dose of niacin
      IR and it causes less flushing. In addition, niacin ER administered once-daily is
      not associated with the increased hepatotoxicity reported with SR formulations.
      Niacin ER has been studied extensively in combination therapy with statins,
      including lovastatin in a recently introduced combination tablet. Myopathy has
      not been a substantial problem in statin/niacin ER combination therapy. Finally,
      a study of niacin ER given to diabetic patients showed only mild trends towards
      increased glycosylated haemoglobin concentrations and a need for additional
      antidiabetic medication. Thus, niacin ER represents an effective and safe option
      in the management of low levels of HDL-C and other lipoprotein abnormalities in a
      variety of settings.

PMID- 15163283
TI  - Rivastigmine in vascular dementia.
AB  - Patients with vascular dementia (VaD) show cholinergic deficits that may result
      in characteristic clinical syndromes for different subtypes of the condition.
      Subcortical VaD is characterised by executive dysfunction and behavioural
      problems, reflecting deterioration of the frontal lobe. Based on limited open
      labelled controlled studies of rivastigmine in VaD, this article aims to
      determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE)
      and butyrylcholinesterase (BuChE), has any effects on the typical symptoms of
      subcortical VaD. Long-term rivastigmine treatment is safe and effective.
      Improvements in domains that characterise subcortical VaD were observed,
      indicating that rivastigmine may have provided targeted treatment in areas of the
      brain that are particularly affected in this patient population. A large, double
      blind study of rivastigmine in patients with VaD is clearly warranted.

PMID- 15163285
TI  - The therapeutic potential of ximelagatran to become the anticoagulant of choice
      in medicine: a review of recently completed clinical trials.
AB  - Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that
      inhibits the final step in the coagulation process - namely, the conversion of
      fibrinogen to insoluble fibrin by thrombin. Recently completed large clinical
      trials have evaluated the efficacy and safety of ximelagatran compared to
      standard anticoagulation therapy with warfarin and heparins in several thrombotic
      disorders including the treatment and prevention of venous thromboembolism
      following major orthopaedic surgery; stroke prevention in atrial fibrillation;
      and after acute myocardial infarction. This article reviews these recent clinical
      trials and explores the therapeutic potential of ximelagatran to become the oral
      anticoagulant of first choice in medicine.

PMID- 15163284
TI  - Rosiglitazone plus metformin: combination therapy for Type 2 diabetes.
AB  - Type 2 diabetes is a common disease associated with an increased risk of long
      term complications, in particular cardiovascular disease. Intervention trials
      have provided evidence that strict metabolic control can substantially reduce the
      burden of the disease. However, in order to accomplish this, the pathogenetic
      defects must be tackled by appropriate therapy. Insulin resistance is a common
      defect in these patients and it is even more severe in those who are obese.
      Insulin resistance not only contributes to impaired glucose homeostasis, but also
      to the development of dyslipidaemia, hypertension, inflammatory response and
      endothelial dysfunction, thus exacerbating the cardiovascular risk. Improvement
      of insulin sensitivity can be obtained with metformin and thiazolidinediones.
      These drugs act through different mechanisms with metformin exerting a prevalent
      effect on the liver and glitazones improving insulin sensitivity in peripheral
      tissue. Because of different mechanisms, the association of the two compounds is
      likely to result in an additive effect. Clinical trials available indicate that
      the combination of the two drugs results in greater improvement in plasma glucose
      concentration and HbA(1c) as compared to single therapy, without increasing the
      occurrence of specific side effects. More recently, the two compounds have been
      associated in the same tablet, thus providing the opportunity for a more
      convenient treatment that may encourage patient compliance and, at the same time,
      provide a tool to assess whether a more aggressive intervention on insulin
      resistance may produce favourable effects on the cardiovascular risk.

PMID- 15163286
TI  - Sirolimus- versus paclitaxel-eluting stents in patients with stenosis in a native
      coronary artery.
AB  - With stenting, restenosis occurs in approximately 25% of patients and the
      incidence is even higher in patients with diabetes, small coronary vessels and
      long lesions. The sirolimus-eluting balloon-expandable stent in the treatment of
      patients with de novo native coronary-artery lesions (SIRIUS) trial, enrolled
      patients with more challenging conditions, including a higher frequency of
      diabetes, more complex lesion morphology and longer lesions and showed benefits
      in all groups. After 240 days, the frequency of stenosis of at least 50% of the
      luminal diameter was 3.2 and 35.4% in the sirolimus and standard stents groups,
      respectively. The TAXUS-IV trial was the first large-scale trial on the safety
      and efficacy of paclitaxel-eluting stents in a broad population of patients and
      lesions, and established the safety and effectiveness of this agent. After 9
      months, there was a mean stenosis of 17% in the paclitaxel group compared to 37%
      of patients treated with a bare stent. Thus, the local delivery of potent cell
      cycle inhibitors (sirolimus, paclitaxel) from stents being used for
      revascularisation dramatically decreases the incidence of restenosis in the
      populations of patients studied so far and represents a major advancement in the
      treatment of coronary artery disease.

PMID- 15163287
TI  - Alterations in colonic barrier function caused by a low sodium diet or ionizing
      radiation.
AB  - This article reviews how cytokines and radiation-induced apoptosis affect the
      barrier function of the colonic pericryptal sheath and thereby colonic crypt
      fluid absorption. A layer of myofibroblasts forming a pericryptal sheath
      surrounds the colonic crypt epithelial cells. The colonic pericryptal
      hypertonicity (250--350 mM NaCl) resulting from Na(+) pumping into the space
      between the crypt epithelial cells and the myofibroblasts provides the driving
      force required to produce the suction tension (5-10 atmospheres) that dehydrates
      feces. [Na(+)] in the pericryptal space and crypt lumen is monitored in vivo with
      a Na(+) ion-sensitive fluorescent dye, Sodium Red. Dietary Na+ restriction
      increases this hypertonicity. The rate of dextran--labeled with fluorescein
      isothiocyanate (FITC--accumulation in the crypt lumen monitors fluid absorption
      by the crypt lumen. The rate of leakage of FITC dextran (10 kDa) across the crypt
      wall reflects its permeability. With low Na(+) intake, there is decreased crypt
      luminal dextran permeability. This decrease in crypt permeability is due to
      increased systemic and local release of angiotensin II and TGF-beta and is
      accompanied by pericryptal growth stimulation with consequent increased
      expression of myofibroblast proteins, smooth muscle actin, collagen 4, and OB
      cadherin. Inhibition of cytokine formation by the angiotensin-converting enzyme
      inhibitor (ACEI) captopril prevents these trophic effects. Colonic fluid
      absorption is inhibited 4 days after whole-body exposure to ionizing radiation of
      >8 Gy. Concurrently, there is loss of the pericryptal myofibroblasts resulting
      from apoptosis, with consequent loss of the barrier function of the pericryptal
      sheath. These effects cause increased rates of dextran leakage across the crypt
      wall and loss of myofibroblast markers. Normal colonic function returns after 10
      days accompanied by repair of the pericryptal sheath. The caspase inhibitor, Z
      VAD Fmk, reduces sheath apoptosis. Longer term irradiation of >8 Gy produces
      overgrowth of the myofibroblasts and fibrosis, which is inhibited by captopril.

PMID- 15163288
TI  - Radiation and cardiovascular diseases.
AB  - Both epidemiological and experimental evidence emphasize the connection between
      radiation exposure and cancer. Little effort has been directed toward finding an
      association between radiation and cardiovascular diseases. Lately, studies on the
      A-bomb survivors and Chernobyl accident victims have indicated that radiation
      doses as low as 0.05-1.0 Gy could be responsible for an increase in the incidence
      of cardiovascular diseases. Exposures to high doses of radiation (approximately
      10-40 Gy) have also been reported to induce atherosclerotic lesions in cancer
      patients undergoing radiotherapy. Earlier studies in experimental animals have
      shown that radiation, mostly at high doses (>5 Gy), could accelerate the
      formation of atherosclerotic lesions. This article provides an up-to-date review
      of the literature connecting cardiovascular diseases to radiation exposures,
      particularly at low doses, and the potential implications of this connection in
      radiation risk assessment.

PMID- 15163289
TI  - Cellular inactivation and chromosomal aberrations: initial damage.
AB  - It has been proposed that unrepaired or misrepaired complex lesions of DNA are
      responsible for cell inactivation and chromosomal aberrations. The detailed
      features of the critical damage and the nature of initiating physical events are
      actively investigated. We studied the role of inner-shell (core) ionizations in
      DNA atoms is studied. Ultrasoft X-rays from LURE synchrotron radiation have been
      used to mimic core events induced by ionizing radiations. For biological matter,
      inner-shell photoionization is indeed the main interaction channel of these
      radiations. Moreover, by tuning the X-ray energy below and above the carbon K
      threshold, it is possible to achieve a two-fold increase in the number of core
      ionizations in DNA for a same dose. Cell survival and chromosome aberrations have
      thus been studied at three iso-attenuated energies: 250, 350, and 810 eV.
      Relative biological efficiencies (RBEs) for cell inactivation and chromosome
      aberrations were found to be strongly correlated with the yields of core events
      in DNA.

PMID- 15163290
TI  - Modification of thymocytes membrane radiooxidative damage and apoptosis by
      eugenol.
AB  - Radiation-induced membrane oxidative damage, generation of reactive oxygen
      species (ROS), and cellular apoptosis, as well as their modification by a natural
      antioxidant from plant source, eugenol, have been investigated in mouse
      thymocytes. Thymocyte suspension was irradiated by gamma-rays, and the
      malondialdehyde (MDA) formation was measured with the thiobarbituric acid
      reactive species (TBARS) method. The results showed an increase in MDA in
      irradiated (2 Gy) thymocytes, which was inhibited in samples treated with
      increasing concentrations of eugenol (10-200 microM) prior to irradiation. The
      concentration of eugenol required to inhibit half of the MDA formation (IC(50))
      in irradiated thymocytes was 100 microM. A dose-dependent increase in the
      generation of ROS was observed in irradiated thymocytes (0.5-200 cGy) as measured
      by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA), which was, however,
      inhibited by eugenol administered before irradiation. Furthermore, experiments
      showed a significant decrease in thymocytes apoptosis by antioxidant as measured
      by annexin-V labeling protocol. The inhibition of apoptosis by membrane-localized
      antioxidants such as eugenol, isoeugenol, and alpha-tocopherol acetate was more
      effective than a cytosolic antioxidant such as ascorbic acid. The results suggest
      an effective prevention of membrane and cellular damage in irradiated thymocytes
      by eugenol. It is inferred that damage to membrane played a significant role in
      radiation-induced cellular apoptotic death, which was markedly modified by
      membrane-specific antioxidants.

PMID- 15163291
TI  - Induction of apoptosis in thymocytes by Hippophae rhamnoides: implications in
      radioprotection.
AB  - Hippophae rhamnoides (RH-3), which has been recently reported to elicit dose
      dependent pro- and antioxidant properties in vitro, induced apoptosis in murine
      thymocytes. In a concentration-dependent manner, RH-3 induced apoptosis in
      thymocytes in ex vivo conditions. The maximum effect was observed with 100
      microg/mL of RH-3. Beyond this dose, the induction of apoptosis was inhibited, as
      seen on the ladder formation. However, apoptotic body formation, another
      indicator of apoptosis, was not manifested when various doses of RH-3 (20-200
      microg/mL) were administered. RH-3 (>100 microg/mL) compacted chromatin in the
      form of densely stained masses, and subsequent treatment with proteinase-K
      loosened them and developed a halo around each mass. RH-3 treatment of cells that
      had already undergone apoptosis induced chromatin compaction, which made the
      ladder invisible. During in vivo experiments in mice, the radioprotective dose of
      RH-3 (30 mg/kg b.w.) induced significant DNA fragmentation in thymocytes studied
      spectrofluorimetrically. RH-3 treatment before irradiation in vivo enhanced
      radiation-induced apoptosis. These results were confirmed by hypodiploid
      population studied flow-cytometrically and also by ladder formation. RH-3
      treatment was prooxidative in nature because it depleted thiols and enhanced
      lipids peroxidation after 8 hours of treatment. The paradox between the
      prooxidant and the antioxidant effects of RH-3 in the context of its overall
      radioprotective efficacy has been explained.

PMID- 15163292
TI  - Radioprotective effect of podophyllotoxin in Saccharomyces cerevisiae.
AB  - Recent reports showed that whole extract of Podophyllum hexandrum was
      radioprotective in mice. Podophyllotoxin is one of the major constituents of the
      whole extract of Podophyllum. In this study we report on the radioprotective
      action of podophyllotoxin in Saccharomyces cerevisiae yeast. Proliferating yeast
      cells pretreated with podophyllotoxin (2.5-5.0 microg/mL) for > or =3 hours
      showed a higher surviving fraction after (60)Co-gamma-irradiation (200-600 Gy)
      than did the irradiated cells not pretreated with podophyllotoxin. The maximum
      increase (2.0 times) in surviving fraction was observed in cells treated with 2.5
      microg/mL podophyllotoxin, 5 hours before (60)Co-gamma-irradiation (400 Gy).
      Podophyllotoxin was not mutagenic or recombinogenic at radioprotective doses (2.5
      microg/mL). A post-irradiation decrease in revertants and gene convertants was
      observed in cells treated with podophyllotoxin (2.5 microg/mL podophyllotoxin, -5
      hours, 400 Gy). This study indicates that podophyllotoxin is radioprotective in
      yeast, and its radioprotective effects in higher eukaryotes would be worth
      investigating.

PMID- 15163293
TI  - Evaluation of radioprotective action of compounds using Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae serves as a model eukaryotic system to screen
      radioprotectors that can be used primarily in radiotherapy as well as in
      occupational workers in nuclear and allied industries. A number of antioxidants
      are suggested to be radioprotectors by virtue of their ability to quench reactive
      oxygen species, but their radioprotective action has not been investigated so
      far. In this study, a number of antioxidants were tested for their efficacy in
      radioprotection using yeast cells. Sulfhydryl compounds (disulfiram at 100 and
      200 microM) and reduced glutathione (10 and 100 mM), purified compounds of plant
      origin, such as curcumin (1 mM, 10 mM, and 100 mM), quercetin (100 and 500
      microM), rutin (100 and 200 microM), ellagic acid (100,200, and 500 microM) and
      gallic acid (100 and 500 microM)-were studied. The results revealed that all
      compounds, except gallic acid, specifically protected normal yeast cells from
      gamma-radiation damage. Using rad 52 mutants, which lack recombinational DNA
      repair pathway, it has been found that protection was solely brought about by
      reducing DNA damage rather than by interfering with DNA repair. Results with DNA
      repair polymerase further substantiated this contention. We conclude that simple
      eukaryotic yeast cells can serve as a test system not only for rapid screening of
      radiomodifiers but also to study their mode of action.

PMID- 15163294
TI  - Relevance of radioprotectors in radiotherapy: studies with tocopherol
      monoglucoside.
AB  - Radioprotective compounds are of importance in clinical radiation therapy,
      because normal tissues should be protected against radiation injury while using
      higher doses of radiation to obtain better cancer control. We investigated the
      radioprotection of cellular DNA in cancer and in various cells and tissues, in a
      murine system following exposure to gamma-radiation and tocopherol monoglucoside
      (TMG) administration. We used single-cell gel electrophoresis (comet assay) and
      studied the progression of murine fibrosarcoma following radiation exposure and
      administration of TMG. The administration of TMG to tumor-bearing mice protected
      the cellular DNA against radiation-induced strand breaks as shown by the decrease
      in comet tail length, tail moment, and percentage of DNA in the tails of the
      cells of normal tissues. The same parameters were not altered in the cells of
      fibrosarcoma. Our results showed that the administration of TMG immediately after
      exposure to gamma-radiation can protect normal tissues against radiation damages
      in tumor-bearing mice. Local gamma-radiation exposure (5 Gy) of the tumor
      retarded the tumor growth. Administration of TMG did not protect cancer cells
      from radiation damage because the growth curves of cancer cells treated with
      radiation alone and those treated with TMG after irradiation were not
      significantly different.

PMID- 15163295
TI  - Protein kinase C: a target for anticancer drugs?

PMID- 15163297
TI  - Aromatase inhibitors in breast cancer.
AB  - The development of aromatase inhibitors for breast cancer therapy is a result of
      successful translational research exploring the biochemical effects of different
      compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo
      aromatase inhibition have revealed a consistent difference with respect to
      biochemical efficacy between the third generation compounds (anastrozole,
      letrozole and exemestane) and the previous, first and second generation drugs,
      corresponding to the improved clinical effects of these compounds as outlined in
      large phase III studies. Thus, endocrine evaluation has been found to be a valid
      surrogate parameter for clinical efficacy. Moreover, the results from these
      studies have added important biological information to our understanding of
      endocrine regulation of breast cancer. Based on the clinical results so far,
      aromatase inhibitors are believed to play a key role in future adjuvant therapy
      of postmenopausal breast cancer patients and potentially also for breast cancer
      prevention. Interesting findings such as the lack of cross-resistance between
      steroidal and non-steroidal compounds should be further explored, as this may add
      additional information to our understanding of breast cancer biology.

PMID- 15163296
TI  - High-resolution serum proteomic features for ovarian cancer detection.
AB  - Serum proteomic pattern diagnostics is an emerging paradigm employing low
      resolution mass spectrometry (MS) to generate a set of biomarker classifiers. In
      the present study, we utilized a well-controlled ovarian cancer serum study set
      to compare the sensitivity and specificity of serum proteomic diagnostic patterns
      acquired using a high-resolution versus a low-resolution MS platform. In blinded
      testing sets, the high-resolution mass spectral data contained multiple
      diagnostic signatures that were superior to the low-resolution spectra in terms
      of sensitivity and specificity (P<0.00001) throughout the range of modeling
      conditions. Four mass spectral feature set patterns acquired from data obtained
      exclusively with the high-resolution mass spectrometer were 100% specific and
      sensitive in their diagnosis of serum samples as being acquired from either
      unaffected patients or those suffering from ovarian cancer. Important to the
      future of proteomic pattern diagnostics is the ability to recognize inferior
      spectra statistically, so that those resulting from a specific process error are
      recognized prior to their potentially incorrect (and damaging) diagnosis. To meet
      this need, we have developed a series of quality-assurance and in-process control
      procedures to (a) globally evaluate sources of sample variability, (b) identify
      outlying mass spectra, and (c) develop quality-control release specifications.
      From these quality-assurance and control (QA/QC) specifications, we identified 32
      mass spectra out of the total 248 that showed statistically significant
      differences from the norm. Hence, 216 of the initial 248 high-resolution mass
      spectra were determined to be of high quality and were remodeled by pattern
      recognition analysis. Again, we obtained four mass spectral feature set patterns
      that also exhibited 100% sensitivity and specificity in blinded validation tests
      (68/68 cancer: including 18/18 stage I, and 43/43 healthy). We conclude that (a)
      the use of high-resolution MS yields superior classification patterns as compared
      with those obtained with lower resolution instrumentation; (b) although the
      process error that we discovered did not have a deleterious impact on the present
      results obtained from proteomic pattern analysis, the major source of spectral
      variability emanated from mass spectral acquisition, and not bias at the clinical
      collection site; (c) this variability can be reduced and monitored through the
      use of QA/QC statistical procedures; (d) multiple and distinct proteomic
      patterns, comprising low molecular weight biomarkers, detected by high-resolution
      MS achieve accuracies surpassing individual biomarkers, warranting validation in
      a large clinical study.

PMID- 15163299
TI  - The role of bisphosphonates in breast and prostate cancers.
AB  - Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to
      hydroxyapatite bone mineral surfaces and their major action is to inhibit
      osteoclast activity and thus bone resorption. In oncology, their role in
      metastatic bone disease is well established, but there is increasing interest in
      their potential role in preventing and treating cancer-induced bone loss and
      their possible anti-tumour effects. Metastatic bone disease is associated with a
      variety of skeletal complications, including pathologic fractures, bone pain,
      impaired mobility, spinal cord compression and hypercalcaemia. Intravenous
      bisphosphonates, particularly zoledronic acid, in conjunction with rehydration,
      are now established as the treatment of choice for hypercalcaemia. For treatment
      of bone pain, it has also been shown that bisphosphonates can be an effective
      supplementary approach to radiotherapy. In breast cancer and myeloma,
      bisphosphonates have now become part of standard therapy to treat and prevent
      skeletal-related events (SRE) and, until recently, treatment was largely with
      intravenous pamidronate or oral clodronate. However, large, randomised,
      multicentre trials using intravenous administration of the highly potent
      bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a
      reduction of 20% in the risk of developing an SRE compared with pamidronate for
      patients with breast cancer. Moreover, these trials have demonstrated, for the
      first time, that a bisphosphonate significantly reduces the occurrence of
      skeletal events in hormone-refractory prostate cancer and in non-small cell lung
      cancer and a range of other solid tumours. Investigations into the potential of
      the relatively low potency bisphosphonate, clodronate, for the prevention of bone
      metastases in breast cancer have produced conflicting data. Further large,
      randomised studies with clodronate and zoledronic acid are planned and until the
      results are available it is not possible to identify a definite adjuvant role for
      bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also
      able to directly affect tumour cells, in addition to their effects on
      osteoclasts, with zoledronic acid being particularly potent. Over recent decades
      there has been a significant improvement in cure rates and survival times in
      certain cancers and the use of chemotherapy and hormone therapy has expanded
      greatly, leading to increasing numbers of long-term survivors who have received
      these treatments. Management of treatment-induced bone loss is therefore assuming
      a greater importance and bisphosphonates represent an attractive treatment option
      in such patients. Several placebo-controlled trials using oral clodronate, oral
      risedronate, intravenous pamidronate and intravenous zoledronic acid have all now
      demonstrated benefits in reducing the loss in bone mineral density.

PMID- 15163298
TI  - Farnesyl transferase inhibitors: the next targeted therapies for breast cancer?
AB  - The ras family of proto-oncogenes are upstream mediators of several essential
      cellular signal transduction pathways involved in cell proliferation and
      survival. Point mutations of ras oncogenes result in constitutively active Ras
      and have been shown to be oncogenic. However, ras activation can occur in the
      absence of ras mutations secondary to upstream receptor activation. The first
      important step in Ras activation is farnesylation by farnesyl transferase, and
      inhibitors of this enzyme have been demonstrated to inhibit Ras signaling, and
      have anti-tumor effects. However, it is now clear that farnesyl transferase
      inhibitors (FTIs) have activity independent of Ras, most likely due to effects on
      prenylated proteins downstream of Ras, which explains their activity in several
      malignancies, including breast cancer, where ras mutations are rare. Several FTIs
      are in clinical development for the treatment of solid tumors. Preclinical
      evidence suggests that FTIs can inhibit breast cancers in vitro and in vivo, and
      a phase II trial of the FTI, R115777, in patients with advanced breast cancer
      produced encouraging results. Based on prior successful outcomes with agents
      targeting the estrogen and epidermal growth factor receptor pathways in breast
      cancer, the FTIs, used alone or more likely with other agents, may be the next
      exciting targeted therapy in breast cancer.

PMID- 15163300
TI  - Genetically defined mouse models that mimic natural aspects of human prostate
      cancer development.
AB  - This review is focused on mouse models for prostate cancer that have been
      designed on the basis of genetic alterations that are frequently found in human
      prostate cancer. It begins with an analysis of the similarities and differences
      in the gross and microscopic anatomy of the mouse and human prostate glands, and
      extends to the pathologies induced in the genetically manipulated mouse prostate
      in comparison with the sporadic development of the disease in humans. Major
      achievements have been made in modeling human prostate cancer in mice in recent
      years. There are models which display slow, temporal development of increasingly
      severe preneoplastic lesions, which are remarkably restricted to the prostate
      gland, a property similar to the aging-related progression of these lesions in
      humans. Other models rapidly progress to local invasive adenocarcinoma, and, in
      some of them metastasis is manifested subsequently with defined kinetics. Global
      assessment of molecular changes in the prostate of the genetically manipulated
      mice is increasingly underscoring the validity of the models through
      identification of 'signature' genes which are associated with the organ-confined
      primary or distant metastases of human prostate cancer. Taken together, various
      'natural' models depicting stages of the disease, ranging from the early
      preneoplastic lesions to metastatic prostate cancer, now provide new tools both
      for exploring the molecular mechanism underlying prostate cancer and for
      development or testing of new targeted therapies.

PMID- 15163301
TI  - Copper deficiency as an anti-cancer strategy.
AB  - Copper is a tightly regulated trace element. Disruptions of copper homeostasis
      are rare and they cause serious disorders such as Wilson's disease and Menkes
      disease. Copper also plays an important role in promoting physiological and
      malignant angiogenesis. Formation of new blood vessels by a tumor enables tumor
      growth, invasion and metastasis. The copper chelator tetrathiomolybdate (TM),
      which quickly and effectively depletes copper stores, is under investigation as
      an anti-angiogenic agent. Promising results in vitro, in pre-clinical animal
      models and in an early (phase I) clinical trial have led to ongoing phase II
      evaluation of TM in patients with advanced cancers.

PMID- 15163302
TI  - Protein kinase A and its role in human neoplasia: the Carney complex paradigm.
AB  - The type 1 alpha regulatory subunit (R1alpha) of cAMP-dependent protein kinase A
      (PKA) (PRKAR1A) is an important regulator of the serine-threonine kinase activity
      catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association
      'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in
      essence the latest form of multiple endocrine neoplasia to be described and
      affects the pituitary, thyroid, adrenal and gonadal glands. Primary pigmented
      nodular adrenocortical disease (PPNAD), a micronodular form of bilateral adrenal
      hyperplasia that causes a unique, inherited form of Cushing syndrome, is also the
      most common endocrine manifestation of CNC. CNC and PPNAD are genetically
      heterogeneous but one of the responsible genes is PRKAR1A, at least for those
      families that map to 17q22-24 (the chromosomal region that harbors PRKAR1A). CNC
      and/or PPNAD are the first human diseases to be caused by mutations in one of the
      subunits of the PKA holoenzyme. Despite the extensive literature on R1alpha and
      PKA, little is known about their potential involvement in cell cycle regulation,
      growth and/or proliferation. The presence of inactivating germline mutations and
      the loss of its wild-type allele in CNC lesions indicated that PRKAR1A could
      function as a tumor-suppressor gene in these tissues. However, there are
      conflicting data in the literature about PRKAR1A's role in human neoplasms,
      cancer cell lines and animal models. In this report, we review briefly the
      genetics of CNC and focus on the involvement of PRKAR1A in human tumorigenesis in
      an effort to reconcile the often diametrically opposite reports on R1alpha.

PMID- 15163303
TI  - Molecular mechanisms of androgen receptor-mediated gene regulation: structure
      function analysis of the AF-1 domain.
AB  - The androgen receptor is a ligand-activated transcription factor that binds DNA
      response elements as a homodimer. Binding sites for the receptor have been
      identified both upstream and downstream of the transcription start site. Once
      bound to DNA, the receptor contacts chromatin remodelling complexes, coactivator
      proteins and components of the general transcription machinery in order to
      regulate target gene expression. The main transactivation domain, termed AF1, is
      located within the structurally distinct amino-terminal domain. This region is
      structurally flexible but adopts a more folded conformation in the presence of
      the binding partner TFIIF, and this in turn enhances subsequent protein-protein
      interactions. Thus, there is likely to be a dynamic interplay between protein
      protein interactions and protein folding, involving AF1, that is proposed to lead
      to the assembly and/or disassembly of receptor-dependent transcription complexes.

PMID- 15163304
TI  - Gene expression profiling in human insulinoma tissue: genes involved in the
      insulin secretion pathway and cloning of novel full-length cDNAs.
AB  - Insulinoma is a clinically common cause of organic hypoglycemia. The prominent
      characteristic of insulinoma is endogenous hyperinsulinism. Until now, the
      molecular biology of human insulinoma has been little understood. In this study,
      gene expression profiling of human insulinoma was established by expressed
      sequence tag (EST) sequencing and cDNA array. A total of 2063 clones were
      obtained, of these, 1589 clones were derived from EST sequencing, 975 clones were
      derived from cDNA array and 501 clones were shared by the two methods. G protein
      alpha-stimulating activity polypeptide (Gsalpha) and carboxypeptidase E (CPE)
      were the most highly expressed genes in human insulinoma, as derived by EST
      sequencing and cDNA array respectively. The genes involved in the protein/insulin
      secretion pathway were strongly expressed in human insulinoma tissue. Meanwhile,
      eight full-length cDNAs of novel genes were cloned and sequenced. The results
      demonstrated the molecular biology of human insulinoma tissue at the level of
      transcript abundance and validated the efficacy of EST sequencing combined with
      cDNA array in the construction of gene expression profiling. In conclusion, the
      predominance of the genes participating in the secretory pathway suggested that
      regulation of secretion might be a major mechanism by which insulin release is
      abnormally increased in patients with insulinomas. It was also concluded that
      overexpression of the Gsalpha gene played an important role in the pathogenesis
      of insulinoma.

PMID- 15163305
TI  - Hormone therapy after endometrial cancer.
AB  - Endometrial carcinoma is listed under the absolute contraindications to hormone
      therapy (HT). According to current opinion, HT after stage I or II is still
      considered an option, and continuous combined oestrogen/progestogen replacement
      therapy (CCEPT) would be recommended. However, up to now, only observational
      studies have been put forward. Although none of these studies have established an
      increased rate of recurrence or mortality, alternatives such as phytopreparations
      and tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should
      be considered for the relief of climacteric complaints. Progestogen-only therapy
      (PT) particularly has been considered. However, the currently discussed possible
      progestogen effects regarding an increased risk of breast cancer have to be taken
      into account. Indeed, the wider discussion about the gestagen effects regarding
      the risk of breast cancer is to be considered. Generally, after hysterectomy, at
      least for patients with cardiovascular risk factors, the preference today is to
      use low-dose oestrogen therapy (patches or gels) instead of CCEPT, and this is
      also now recommended for patients after endometrial cancer. This is to be noted
      because of the risk factors for endometrial carcinoma, such as hypertension,
      obesity, polycystic ovary syndrome (PCO) and diabetes mellitus. However, each
      form of HT should be only exceptionally recommended, and the patients must be
      informed about the risks that exist and the use of alternatives.

PMID- 15163306
TI  - FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.
AB  - The aim of this work was to compare mean concentrations of gonadotropins in serum
      and fluid from malignant and benign ovarian tumors. We enrolled 126 patients
      diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors
      (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary.
      Premenopausal and postmenopausal subgroups were formed in each group. The
      concentration of FSH and LH was measured in serum and tumor fluid and the
      serum/tumor fluid ratio was calculated. The results in each group were compared
      and the sensitivity, specificity, positive and negative predictive values were
      determined. Mean concentrations of both gonadotropins in ovarian cancer fluid
      were significantly higher than in the remaining groups (P ranged from <0.005 to
      <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91,
      LH=4.19). Our findings support the hypothesis that gonadotropins are involved in
      ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios
      could be of value in the differential diagnosis of functional and organic cysts
      of the ovary.

PMID- 15163307
TI  - Measurement of somatostatin receptor subtype 2 mRNA in breast cancer and
      corresponding normal tissue.
AB  - Somatostatin analogs are effective in inhibiting growth of human breast cancer
      cell lines. These antiproliferative effects are mediated by specific receptors
      located on cell membranes. The somatostatin receptor subtype 2 (sst2) is the
      principal mediator of somatostatin effects in normal and cancer cells, and its
      presence has already been demonstrated in breast cancer. The purpose of our study
      was to evaluate the clinical relevance of the expression of sst2 by quantifying
      its mRNA in a large group of infiltrating breast cancers and their corresponding
      normal tissues. The expression of sst2 mRNA was measured with quantitative real
      time RT-PCR in 169 breast cancers and in their corresponding unaffected tissues.
      We evaluated the association of sst2 expression with the commonest clinical
      pathologic features of breast cancer. The correlation with a marker of cell
      proliferation (Ki-67) and with receptor concentration was also evaluated. In
      cancer tissues, we found that the absolute concentrations of sst2 mRNA were
      significantly higher in estrogen receptor (ER)-positive samples (P=0.002) as well
      as in lymph-node-negative cancers (P=0.04) (Student's t-test or one-way ANOVA).
      In addition, sst2 mRNA was significantly higher in breast cancers than in
      corresponding unaffected tissues (P=0.0002). However, when the clinical
      pathologic parameters were considered, this gradient maintained its statistical
      significance only in tumors expressing positive prognostic markers, such as the
      presence of ER (P=0.0005) and progesterone receptors (PgR) (P=0005), and the lack
      of lymph-node involvement (P=0.0003). The same difference was also significant in
      postmenopausal women (P=0.001) and in T1 patients (P=0.001). In addition, sst2
      mRNA expression was significantly higher (P=0.008) in low-proliferating breast
      cancers. Finally, we found that the quantitative expression of sst2 mRNA was
      directly related to the PgR concentration in breast cancer tissues (P<0.001). Our
      data seem to indicate that an upregulation of sst2 gene expression is a common
      feature of breast cancers which, on the basis of conventional predictive
      parameters, are expected to have a better prognosis. Featuring a possible role of
      somatostatin analogs in combined endocrine therapies for breast cancer, our
      results seem to confirm that the sst2 status of the tumor should be previously
      investigated.

PMID- 15163308
TI  - Differential expression of menin in sporadic pituitary adenomas.
AB  - Pituitary adenomas represent one of the key features of multiple endocrine
      neoplasia type 1. The gene involved in this syndrome (MEN1) is a putative tumor
      suppressor, that codes for a 610-amino acid nuclear protein termed 'menin'.
      Analyses of sporadic pituitary adenomas have so far failed to reveal MEN1
      mutations or defects in MEN1 transcription in these tumors. In the present study
      we detected menin protein expression in a panel of normal and tumoral pituitary
      tissues, using a monoclonal antibody against the carboxy-terminus of menin. In
      the normal human pituitary gland, strong nuclear staining for menin was
      detectable in the majority of the endocrine cells of the anterior lobe, without a
      clear association with a particular hormone-producing type. In sporadic pituitary
      adenomas, menin expression was variable, with a high percentage of cases
      demonstrating a significant decrease in menin immunoreactivity when compared with
      the normal pituitary. Interestingly, metastatic tissues derived from one
      pituitary carcinoma had no detectable menin levels. Altogether, our data provide
      the first information regarding the status of menin expression in human normal
      and neoplastic pituitary as determined by immunohistochemistry (IHC).

PMID- 15163309
TI  - Chronic thyrotropin-suppressive therapy with levothyroxine and short-term overt
      hypothyroidism after thyroxine withdrawal are associated with undesirable
      cardiovascular effects in patients with differentiated thyroid carcinoma.
AB  - To evaluate cardiovascular functionality in patients with thyroid cancer, we have
      performed echocardiography and ambulatory blood pressure monitoring in 19 women
      with differentiated thyroid carcinoma during thyroxine withdrawal, at three time
      points: the last day on TSH-suppressive thyroxine doses (subclinical or mild
      hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free
      triiodothyronine (FT3) levels), and before 131I whole body scanning (overt
      hypothyroidism). Twenty-one healthy euthyroid women served as controls. When
      compared with the values at visit 2, when patients had normal serum FT4 and FT3
      levels, night-time systolic and mean blood pressure were increased when the
      patients were mildly hyperthyroid, and night-time systolic, diastolic and mean
      blood pressure were increased during overt hypothyroidism. The proportion of
      nondippers (absence of nocturnal decline in blood pressure) was markedly
      increased compared with healthy controls (7%), when patients were hyper- or
      hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and
      FT3 levels (12%). No changes were observed in office blood pressure or in daytime
      ambulatory blood pressure readings. Diastolic function worsened during thyroxine
      withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A
      ratio and the isovolumic relaxation time increased), and cardiac output decreased
      in parallel with the decrease in heart rate and systolic blood flow. In
      conclusion, the chronic administration of TSH-suppressive doses of thyroxine and
      the withdrawal of thyroxine frequently used for the management of differentiated
      thyroid carcinoma, are associated with undesirable cardiovascular effects.

PMID- 15163310
TI  - Postoperative calcitonin study in medullary thyroid carcinoma.
AB  - Calcitonin (CT) is a sensitive marker for medullary thyroid carcinoma.
      Normalization of early postoperative CT level is a favorable prognostic factor.
      The aim of this study was to establish the prognostic value of CT-level kinetics
      by preoperative tumor stage and postoperative elimination rate. Blood serum from
      22 medullary thyroid carcinoma (MTC) patients without remote metastases was
      assayed. A commercial RIA DSL-1200 test was used to assay CT levels. Basal CT< or
      =42 pg/ml and stimulated CT< or =120 pg/ml were considered normal. The patients
      were divided into three groups according to the intensity of the postoperative CT
      level reduction in blood serum. Group 1 comprised patients who showed basal CT
      normalization within the first 2-3 days after surgery. Group 2 included those
      patients with slow (from 2 to 4 weeks) CT-level normalization. Group 3 included
      patients with CT levels that reduced within 14 days, but subsequently increased.
      Preoperative basal CT varies from 216 to 1654 pg/ml and depends on tumor-node
      metastasis (TNM) stage. In seven patients, no basal CT decrease to normal values
      was observed; in five of these patients, disease recurrence was detected 2-6
      months after surgery. In the group with slowly decreasing CT levels, no strong
      correlation between preoperative CT level and the postoperative time to
      normalization of basal and peak CT could be established; this may be due to the
      small number of patients. Our study showed that preoperative CT level depended on
      the disease stage. Postoperative CT elimination rate is independent of
      preoperative CT level. Postoperative increase in the basal or stimulated CT level
      is an unfavorable prognostic factor, implying disease recurrence.

PMID- 15163312
TI  - Heat shock protein 70 (Hsp70) subtype expression in neuroendocrine tissue and
      identification of a neuroendocrine tumour-specific Hsp70 truncation.
AB  - In order to identify neuroendocrine tumour-specific protein expression, we
      generated monoclonal antibodies (mAbs) with a tumour-related reaction pattern
      using a human insulinoma as immunogen. One of the generated mAbs (mAb 1D4)
      exhibited striking immunoreactivity against various neuroendocrine tumours
      without staining pancreatic islets of Langerhans. Furthermore, mAb 1D4
      immunostained a characteristic subtype of hypothalamic neurones. Using two
      dimensional (2-D) gel electrophoresis, mAb 1D4 immunoblotting and mass
      spectrometry, heat shock protein 70 (Hsp70) isoforms were identified as the mAb
      1D4-specific antigen. In hypothalamic tissue, the presence of two different Hsp70
      isoforms (Hsp70-8 and Hsp70-1) was revealed by 2-D gel immunoblots and
      consecutive mass spectrometric peptide analysis. In contrast, insulinoma and
      other neuroendocrine tumours displayed solely Hsp70-8 expression. Moreover, the
      tumour-specific presence of an additional mAb 1D4 immunoreactive protein of 40
      kDa was observed in eight out of eight tested neuroendocrine tumours. For this
      variant, exclusively, peptides derived from the C terminus excluding the 299
      amino-terminal residues were detected. In cultured tumour-derived fibroblasts,
      expression of the truncated Hsp70-8 subtype was not present. In conclusion, we
      have demonstrated a neuroendocrine tumour-specific expression pattern of Hsp70
      isoforms and identified an as yet unknown N-terminally truncated Hsp70-8 variant.

PMID- 15163311
TI  - Clinico-pathological significance of cell-type-specific loss of heterozygosity on
      chromosome 7q21: analysis of 318 microdissected thyroid lesions.
AB  - A careful pathological examination often reveals the presence of different
      lesions at various stages of tumor progression and invasion, even in those
      thyroid glands presenting with solitary nodules. Each thyroid lesion is composed
      of many different cell types, reflecting the marked heterogeneity of normal
      thyroid tissue. Among the different chromosome regions altered in thyroid tumors,
      7q21 appears to be specifically involved in malignant tumors, especially of the
      follicular type. This study was conducted to analyze the loss of heterozygosity
      (LOH) pattern at 7q21 in pure populations of cells from each single lesion
      harbored in surgically removed thyroid glands, and to evaluate its clinical
      significance. One hundred and forty-two thyroid glands were examined, all
      showing, as a common trait, a goitrous appearance associated with one single
      lesion in 114 cases and with more than one in the remaining 28 cases. A total
      number of 318 lesions was analyzed, consisting of 142 goiters (TG), 48
      hyperplasias (TH), 80 adenomas (TA) and 48 carcinomas (TC). Five different types
      of cells were isolated by laser capture microdissection from each lesion. DNA was
      analyzed by PCR and polyacrylamide gel electrophoresis in search of LOH affecting
      five microsatellite markers, D7S660, D7S630, D7S492, D7S657, and D7S689. We
      detected LOH at 7q21 not only in thyroid malignant tumors but also in benign
      lesions. Allelic loss occurred exclusively in dark nucleus and eosinophilic
      cytoplasm cells, commonly observed in the follicular type of lesions. In these
      types of lesions allelic loss frequency increases along with neoplastic
      transformation (9% in TG, 41% in TH, 68% in TA and 100% in TC), and is directly
      correlated with thyroid gland volume as well as with the presence of multiple
      lesions. The highest LOH rate was observed for D7S492, indicating that the
      recurrent region of deletion was localized at the corresponding genetic locus at
      7q21.2, in the same position where the common fragile site FRA7E was previously
      mapped. LOH at this locus represents an early event in the development of
      follicular TC and is associated with intense growth of thyroid glands.

PMID- 15163314
TI  - Molecular diagnosis of haemoglobin disorders.
AB  - The haemoglobinopathies refer to a diverse group of inherited disorders
      characterized by a reduced synthesis of one or more globin chains (thalassaemias)
      or the synthesis of a structurally abnormal haemoglobin (Hb). In prevalent
      regions, the thalassaemias often coexist with a variety of structural Hb variants
      giving rise to complex genotypes and an extremely wide spectrum of clinical and
      haematological phenotypes. An appreciation of these phenotypes is needed to
      facilitate the definitive diagnosis of the causative mutations to inform
      management and counselling. Haematological and biochemical investigations, and
      family studies provide essential clues to the different interactions and are
      fundamental to DNA diagnostics of the Hb disorders. With the exception of a few
      rare deletions and rearrangements, the molecular lesions causing
      haemoglobinopathies are all identifiable by PCR-based techniques. Although a full
      spectrum of >1000 mutations causing haemoglobinopathies has been documented, in
      practice only a limited number are associated with disease states and clinical
      significance. Furthermore, each at-risk ethnic group has its own combination of
      common Hb variants and thalassaemia mutations. Prior identification of the ethnic
      origin is thus an important part of the diagnostic strategy which becomes less
      reliable in the UK because of the large ethnic mix. Although the current approach
      using a combination of different PCR-based techniques seems to work in most
      laboratories, practice pressures with the imminent implementation of universal
      antenatal screening for clinically significant Hb disorders in the UK will
      require a higher throughput approach for DNA diagnostics in the near future. The
      complex mutational spectrum and the compactness of the globin genes places them
      in an ideal position for the different non-gel based analytical platforms.

PMID- 15163313
TI  - Recombinant human mast-cell chymase: an improved procedure for expression in
      Pichia pastoris and purification of the highly active enzyme.
AB  - Human mast-cell chymase (EC 3.4.21.39) is a chymotrypsin-like serine protease
      that is stored in and released from mast-cell granules. This enzyme has been
      expressed in Pichia pastoris by homologous recombination of the cDNA coding for
      the mature active chymase into the Pichia genome. Cells producing the highest
      levels of recombinant human chymase were selected by activity screening and they
      were grown in a fermentor. Methanol induction resulted in the secretion of active
      chymase into the Pichia growth media and increasing levels of enzyme were
      detected in the media for 5 days. Active enzyme was purified from the culture
      media with a 22% yield of activity by a simple two-step procedure involving
      hydrophobic-interaction chromatography followed by affinity chromatography on
      immobilized heparin. The major peak from the heparin column contained a single
      band of 30.6 kDa on SDS/PAGE. The purified recombinant human chymase was 96%
      active and the yield was 2.2 mg/l of growth media.

PMID- 15163315
TI  - A standardized procedure for quantitation of CD11b on polymorphonuclear
      neutrophil by flow cytometry: potential application in infectious diseases.
AB  - An up-regulation of the surface marker CD11b has been demonstrated during
      polymorphonuclear (PMN) cell activation. CD11b over-expression is often
      associated with inflammation and is considered as an early marker of infection.
      However, the absence of standardized assay and the variability of preanalytical
      settings leading to PMN artifactual activation have compromised the interest of
      this marker. In the present study a standardized quantitative flow cytometry
      assay directly performed in whole blood has been used to determine CD11b
      expression on PMN cells. The results indicate that quantitative flow cytometry
      can provide consistent CD11b density values between laboratories provided that a
      calibration system is used including specific calibrators, reagents and
      protocols. This method allowed us to evidence an up-regulation of CD11b
      expression for infected patients. This quantitation is a standardized and
      potentially useful method in clinical situations implying quantitative CD11b
      expression variations.

PMID- 15163316
TI  - Flow cytometric analysis of fetal hemoglobin in erythroid precursors of beta
      thalassemia.
AB  - Fetal hemoglobin (HbF), the major hemoglobin species in fetal life, drops to <1%
      in normal adults, where it is restricted to a few 'F-cells', which may increase
      in various acquired and genetic conditions, including thalassemia. Using flow
      cytometry, we studied the percentage of HbF-containing cells and their HbF
      content in RBC, reticulocytes (retics) and normoblasts (NRBC) present in the
      peripheral blood of patients with beta-thalassemia. Thiazol orange, a nucleic
      acid-specific dye, and anti-CD45 antibodies identified the various blood cells
      and antihuman HbF antibodies quantitated HbF. The results indicated that F-RBC
      were more numerous in beta-thalassemic (both transfused and nontransfused)
      patients than in normal donors, but, in most cases, their HbF content was
      comparable, suggesting that increased HbF in thalassemia is mainly due to higher
      %F-cells rather than an increased HbF per cell. Among the retics, the %F-cells
      and their HbF content were highest in immature retics and decreased with
      maturation to levels of RBC. This may reflect preferential maturation of F-retics
      into RBC in the circulation. The NRBC population contained the lowest %F-cells.
      This could be due to preferential maturation of F-NRBC, having more normal
      phenotype than non-F-NRBC, in the bone marrow into F-retics, while non-F-NRBC
      enter the circulation.

PMID- 15163317
TI  - Evaluation of ADVIA 120 CSF assay (Bayer) vs. chamber counting of cerebrospinal
      fluid specimens.
AB  - The ADVIA 120 cerebrospinal fluid (CSF) assay (Bayer; Bayer Corp., Tarrytown, NY,
      USA) provides a new, automated analysis of CSF specimens. We evaluated this
      method by comparing its performance with classic chamber counting and microscopic
      analysis of CSF samples.

PMID- 15163318
TI  - Performing bone marrow biopsies with or without sedation: a comparison.
AB  - Although intravenous sedation (ISED) in addition to a local anaesthetic (LA) is
      commonly used in the performance of a bone marrow aspirate and trephine (BMAT),
      it is not clear under what circumstances and in which way sedation may be most
      beneficial. In this study, information was gathered using a questionnaire, from
      112 patients shortly after undergoing BMAT; the duration of the procedures and
      the length of the biopsy cores were measured and any complications noted. Most
      patients (68%) chose to receive LA only, and almost all (74/76) were happy with
      their decision. Patients who received sedation gave lower pain scores than
      patients receiving LA only (1 vs. 3) and were found to have lower levels of
      apprehension at the thought of having a repeat procedure. Patients having a
      repeat BMAT showed a slightly increased preference for having sedation compared
      with patients who were undergoing it for the first time. There is some concern
      that guidelines regarding the use of ISED for procedures other than BMAT are not
      always adhered to, and current practice may be best revealed by a large-scale
      audit of sedation practice for the performance of BMAT. Patients should be given
      the choice of having ISED if the appropriate resources are available, but in most
      cases the additional small risk of receiving sedation can be avoided.

PMID- 15163319
TI  - In patients who have stainable iron in the bone marrow an elevated plasma
      transferrin receptor value may reflect functional iron deficiency.
AB  - Elevated transferrin receptor (TfR) concentration may be either because of iron
      deficiency or an increased rate of erythropoiesis. We have studied the
      relationship between elevated TfR and advanced RBC and reticulocyte indices in an
      unselected population of hospitalized patients. The iron status in 95 consecutive
      hospitalized patients was assessed using bone marrow aspirate examination and
      analysis of the RBC and reticulocyte indices was performed using the Advia 120
      haematology system. Of the 95 patients, a total of 17 had no stainable iron in
      the bone marrow and most of them also had an elevated TfR. Of the 78 patients
      with stainable iron stores, 15 also had an elevated TfR concentration (> or =2.4
      mg/l). Six of them also had an elevated %HYPOm (> or =3.4%), and therefore were
      regarded as having functional iron deficiency. We evaluated the possible causes
      of elevated TfR concentrations in patients having stainable iron in the bone
      marrow, and this study suggests that functional iron deficiency explains a
      considerable proportion of these cases.

PMID- 15163320
TI  - Splenectomy results in patients with idiopathic thrombocytopenic purpura: 10
      years of experience in Turgut Ozal Medical Center.
AB  - The standard treatment for immune thrombocytopenic purpura (ITP) is
      corticosteroid therapy. In patients who are refractory to this treatment,
      splenectomy is the most usual therapy. Between 1993 and 2003, 125 patients were
      diagnosed with ITP in the Inonu University School of Medicine, Department of
      Haematology. Twenty-one of these patients who did not respond to steroids,
      underwent splenectomy. Of these 21 patients, 12 achieved complete and three
      achieved partial haematological responses, while the remaining six did not
      respond. Four of these six patients responded to drugs such as azathioprine and
      danazol, while the others were totally refractory. Only one of our patients
      showed fatal complications either during or after the surgery. Our results after
      10 years experience demonstrate that splenectomy is an effective and safe
      treatment for ITP patients who are refractory to steroids.

PMID- 15163321
TI  - Usefulness of synthetic phospholipid in measurement of activated partial
      thromboplastin time: a new preparation procedure to reduce batch difference.
AB  - Commercial activated partial thromboplastin time (APTT) reagents prepared with
      phospholipid extracted from animal or plant sources often differ in their
      response to heparin and coagulation factors and in their reference values. It is
      also known that there are variations in phospholipid composition and preparation
      procedure. The present study attempted to demonstrate that an APTT reagent based
      on synthetic phospholipids (phosphatidylethanolamine, phosphatidylcholine and
      phosphatidylserine), which are substances of high purity and homogeneity, reduces
      batch-to-batch difference when compared with two traditional APTT reagents
      derived from rabbit brain and soybean. Three types of APTT reagent (SYN-APTT, RBT
      APTT, SOY-APTT), prepared respectively from synthetic phospholipid, rabbit brain,
      and soybean, were tested. The total batch-to-batch difference was coefficient of
      variation (CV) 0.7-2.4% in the five reagents prepared from synthetic phospholipid
      (SYN-APTT), but CV 1.5-10.3% in the two traditional reagents (RBT-APTT and SOY
      APTT). Additionally, high-performance liquid chromatography (HPLC) analysis
      showed clear variation in the phospholipid composition of the RBT-APTT and SOY
      APTT reagents. In conclusion, the SYN-APTT reagent derived from synthetic
      phospholipid was shown to reduce batch-to-batch difference, and we therefore
      suggest that synthetic phospholipid is a substance useful in the preparation of
      APTT reagent and could contribute to stability of supply and uniform diagnosis.

PMID- 15163322
TI  - Prevalence of seromarkers of HBV and HCV among blood donors in eastern Saudi
      Arabia, 1998-2001.
AB  - The prevalence of serological markers of HBV and HCV were determined for blood
      donors in eastern Saudi Arabia. Between 1998 and 2001, 13,443 donors (10,778
      Saudi and 2665 non-Saudi), were screened for HBsAg, anti-HBc Ab, and anti-HCV Ab
      using commercial kits. There was a steady decrease in the HBsAg (2.58 and 1.67%),
      anti-HBc rates (15.32 and 9.15%), and anti-HCV (1.04 and 0.59%) rates between
      1998 and 2001, respectively. However, there was a marked difference between Saudi
      and non-Saudi donors with regard to anti-HBc (P < 0.001) and anti-HCV (P < 0.01),
      but not HBsAg prevalence rates in the same time period.

PMID- 15163323
TI  - Immediate haemostasis with recombinant factor VIIa for haemorrhage following
      Hickman line insertion in acute myeloid leukaemia.
AB  - Bleeding following Hickman line insertion is not uncommon but can be life
      threatening, especially in the presence of coagulopathy and thrombocytopenia
      following chemotherapy. Treatment to control the bleeding can be challenging and
      treatment options are limited. We present our experience of a patient who had
      persisting haemorrhage immediately following Hickman line insertion for
      administration of chemotherapy for relapsed acute myeloid leukaemia. Haemostasis
      could not be achieved after FFP and platelet administration. A single dose of
      recombinant factor VIIa (rhFVIIa) stopped the bleeding immediately, avoiding the
      need for surgical intervention or line removal. Our experience indicates rhFVIIa
      may be an effective option for bleeding related to Hickman line insertion.

PMID- 15163324
TI  - Acute promyelocytic leukaemia presenting as postpartum haemorrhage.
AB  - Acute leukaemia is encountered rarely in obstetric practice, occurring once in
      every 100,000 pregnancies. Such cases are usually diagnosed in the second and
      third trimesters. We describe a patient who developed a postpartum haemorrhage
      (PPH) as the presenting feature of acute promyelocytic leukaemia, which, to the
      best of our knowledge, has not been reported previously.

PMID- 15163325
TI  - A very rapid multiplex polymerase chain reaction for simultaneous detection of
      factor V Leiden and G20210A prothrombin mutation.

PMID- 15163326
TI  - Values of the parameter immature reticulocyte fraction in elite athletes.

PMID- 15163327
TI  - Age-related changes in testosterone and the role of replacement therapy in older
      men.

PMID- 15163328
TI  - Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies
      (ANCA) in patients with Graves' disease.
AB  - OBJECTIVE: Propylthiouracil treatment of Graves' disease has been postulated to
      provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We
      aimed to investigate whether carbimazole therapy was also associated with
      increased risk of ANCA. DESIGN: The occurrence of ANCA and the relationship to
      thionamide treatment was investigated in a cross-sectional study in a consecutive
      series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis
      and 649 normal euthyroid subjects. MEASUREMENTS: ANCA was measured by indirect
      immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for
      proteinase 3 and myeloperoxidase-ANCA. RESULTS: The prevalence of ANCA, as
      measured by IIF, was increased in the Graves' disease cohort (19.9%) compared
      with euthyroid controls (4.6%; P < 0.001). The prevalence of MPO-ANCA (measured
      by ELISA) was also increased in Graves' disease (P = 0.019). ANCA prevalence was
      more strongly associated with propylthiouracil treatment than carbimazole (P =
      0.0265), although risk of ANCA was also higher in Graves' patients treated with
      carbimazole than controls (RR 2.2, P < 0.0001). ANCA positivity was not increased
      in patients with Hashimoto's thyroiditis. CONCLUSION: This study revealed a high
      prevalence of ANCA in treated patients with Graves' disease but not in those with
      Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA
      development was associated with propylthiouracil usage to a greater extent than
      carbimazole. These findings suggest that the altered immune environment
      associated with autoimmune thyroid disease is not sufficient to develop ANCA but
      treatment with thionamides is important in promoting ANCA development.

PMID- 15163329
TI  - Comparison of single daily dose of methimazole and propylthiouracil in the
      treatment of Graves' hyperthyroidism.
AB  - OBJECTIVE: The present study was to compare the efficacy of a single daily dose
      of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves'
      hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in
      the treatment of hyperthyroidism. Previous studies in the treatment of
      hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a
      more favourable result with MMI. However, the efficacy of a single daily dose of
      PTU was inconsistent. In this study, we examined the therapeutic efficacy of
      single daily doses of MMI and PTU on the change of thyroid hormones and
      thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with
      newly diagnosed Graves' hyperthyroidism were randomly divided into two groups,
      each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12
      weeks. The therapeutic efficacy was determined by serum total triiodothyronine
      (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb
      levels at baseline and at the end of 4, 8 and 12 weeks during the study period.
      RESULTS: There was no significant difference in baseline thyroid function
      parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were
      significantly lower than those of the PTU-treated group after 4 weeks and through
      the end of the study. MMI also has superior effect on reducing serum TRAb levels
      than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12
      week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was
      much more effective in the induction of euthyroidism than a single daily dose of
      150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once
      daily regimen of antithyroid drug is considered for the treatment of Graves'
      hyperthyroidism.

PMID- 15163330
TI  - Vitamin A and iron supplementation is as efficient as hormonal therapy in
      constitutionally delayed children.
AB  - OBJECTIVE: To assess the effect of nutritional supplementation on growth and
      puberty in constitutionally delayed children. PATIENTS: One hundred and two boys,
      13.6-15.5 years of age, who were referred because of short stature and delayed
      puberty. METHODS: The boys were randomly allocated to one of the following
      treatment groups: oxandrolone therapy, 5 mg/day for 6 months (n = 15),
      testosterone depot, 100 mg monthly for 3 months (n = 15) or for 6 months (n =
      20), nutritional programme (n = 17), oxandrolone and nutritional programme (n =
      15) or passive observation (n = 20). Boys in the nutritional programmes received
      12 mg/day iron and 6000 IU/week of vitamin A. Outcome measurements were of
      height, weight, pubertal signs, dietary intake, serum vitamin A, iron, GH and IGF
      1. RESULTS: Six months of vitamin A supplementation induced growth acceleration
      similar to that seen in the oxandrolone- and testosterone-treated children, and
      significantly greater than in the observation group (9.3 +/- 2.9 vs. 4.0 +/- 0.9
      crn/yr, P < 0.001). Whereas in the vitamin A-supplemented group, puberty
      (increase in testicular volume >/= 12 ml) was induced within 12 months. In all
      testosterone-treated patients, pubic hair was noted within 3 months and a
      testicular volume of >/= 12 ml was observed 9-12 months after the initiation of
      therapy. No pubertal signs were noted in the observation group during this time.
      CONCLUSIONS: Subnormal vitamin A intake is one of the aetiological factors in
      delayed pubertal maturation. Supplementation of both vitamin A and iron to normal
      constitutionally delayed children with subnormal vitamin A intake is as
      efficacious as hormonal therapy in the induction of growth and puberty.

PMID- 15163331
TI  - Conventional glucocorticoid replacement overtreats adult hypopituitary patients
      with partial ACTH deficiency.
AB  - BACKGROUND: Glucocorticoid therapy is associated with potentially serious side
      effects, but there is no information available regarding glucocorticoid
      requirement in adult hypopituitary patients with partial ACTH deficiency.
      SUBJECTS: Ten male adult hypopituitary patients with partial ACTH deficiency,
      baseline plasma cortisol > 200 nmol/l but a peak stimulated cortisol < 500 nmol/l
      and 10 matched healthy male control volunteers participated. DESIGN: Patients
      were assigned, in a random order, to a cross-over protocol of treatment for 1
      week with full dose hydrocortisone (10 mg twice daily), half-dose hydrocortisone
      (5 mg twice daily), or no treatment. All patients completed all three of the
      treatment limbs. MEASUREMENTS: Following each treatment schedule, patients
      underwent an 11-h cortisol day curve (CDC), and the results were compared with
      those from the 10 control volunteers on no glucocorticoid treatment. RESULTS: The
      integrated CDC values were significantly higher in patients taking a full dose of
      hydrocortisone compared to controls (P < 0.001). There was no significant
      difference in the integrated CDC between patients on half-dose (P = 0.37) or no
      hydrocortisone treatment (P = 0.13), compared to control subjects. Peak
      postabsorption cortisol values were higher in patients receiving full-dose
      hydrocortisone treatment compared to controls (P < 0.001). There was no
      significant difference in plasma sodium concentration, blood pressure or
      corticosteroid-binding globulin between patients on any treatment schedule and
      controls. CONCLUSION: Adult patients with pituitary disease and partial ACTH
      deficiency have a cortisol secretory pattern comparable to that of healthy
      controls. Conventional full-dose replacement with 10 mg twice daily of
      hydrocortisone produces hypercortisolaemia, whereas half-dose produces a CDC that
      is not statistically different from that of healthy controls. The results suggest
      that current conventional glucocorticoid replacement overtreats patients with
      partial ACTH deficiency under normal unstressed physiological conditions.

PMID- 15163332
TI  - Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves'
      disease.
AB  - OBJECTIVE: The aim of this study was twofold: first to investigate the presence
      of extraocular muscle antibodies (EMAb) in sera of Graves' patients with
      ophthalmopathy characterized by clinical extraocular muscle (EM) involvement;
      second to evaluate in Graves' patients without ophthalmopathy whether
      longitudinal variations of EMAb have a predictive role for the development of eye
      disease. PATIENTS: We evaluated sera of Graves' patients previously tested for
      G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe
      ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with
      inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19
      Graves' patients without ophthalmopathy previously tested for anti-GS2 (G2sAb)
      and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up,
      four of them did not develop ophthalmopathy (group 3a), and 15 did: seven
      developed eye disease (group 3b) with clinical EM involvement. In particular,
      moderate disease and clinical activity score (CAS) >/= 4 in four of them, severe
      ophthalmopathy and CAS </= 1 in three were observed. The remaining eight patients
      showed moderate ophthalmopathy and CAS >/= 4 without EM involvement (group 3c).
      MEASUREMENTS: EMAb were evaluated in all samples by indirect immunofluorescence
      method. RESULTS: EMAb were detected in 13 out of 18 patients (72.2%) in group 1
      (titre 1/32-1/128) and in five out of 14 patients (35.7%) in group 2 (titre 1/2
      1/8). As regards to group 3, at the start of the study EMAb were detected in 13
      out of 19 patients (72%) at titres 1/2-1/8; during the follow-up they became or
      persisted negative in all patients in group 3a, while they increased at titres
      ranging from 1/64 to 1/128 in all patients in group 3b before the onset of
      ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8
      1/16) of EMAb before the onset of eye disease, while four patients were negative
      during the entire follow-up. CONCLUSIONS: Our results indicate that EMAb are a
      good marker of ophthalmopathy with EM involvement and their titre is higher in
      patients with active than in those with inactive disease. Thus, even if our
      results must be confirmed on a larger cohort of patients, the increase of EMAb in
      patients with Graves' disease could be considered as a risk factor for the
      development of ophthalmopathy with subclinical/clinical EM impairment. In this
      connection we propose the evaluation of EMAb, in Graves' patients with
      subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the
      EM inflammatory process.

PMID- 15163333
TI  - Ghrelin does not mediate the somatotroph and corticotroph responses to the
      stimulatory effect of glucagon or insulin-induced hypoglycaemia in humans.
AB  - OBJECTIVE: Acylated ghrelin, a gastric peptide, possesses a potent GH- but also
      significant ACTH/cortisol-releasing activity mediated by the activation of GH
      secretagogue receptors (GHS-R) at the hypothalamus-pituitary level. The
      physiological role of ghrelin in the control of somatotroph and corticotroph
      function is, however, largely unclear. Glucagon is known to induce a clear
      increase of GH, ACTH and cortisol levels in humans, at least after intramuscular
      administration. In fact, glucagon is considered to be a classical alternative to
      insulin-induced hypoglycaemia (ITT) for the combined evaluation of the function
      of GH and the hypothalamus-pituitary-adrenal (HPA) axis. We aimed to clarify
      whether ghrelin mediate the GH and corticotroph responses to intramuscular
      glucagon or ITT, which has recently been reported able to induce a surprising
      ghrelin decrease. SUBJECTS: To this aim we enrolled six normal young male
      subjects [age (mean +/- SD): 29.0 +/- 8.0 years, body mass index (BMI) 21.9 +/-
      2.5 kg/m(2)]. DESIGN AND MEASUREMENTS: In all the subjects we studied ghrelin,
      GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0.017 mg/kg
      intramuscularly), ITT (0.1 IU/kg insulin intravenously) or saline administration.
      RESULTS: Saline infusion was not followed by any significant variation in
      ghrelin, GH and glucose levels while ACTH and cortisol showed the expected
      spontaneous morning trend toward a decrease. GLU administration increased (P <
      0.01) circulating GH, ACTH and cortisol as well as insulin and glucose levels.
      ITT induced an obvious increase (P < 0.01) of GH, ACTH and cortisol levels. The
      ITT-induced increases in GH and ACTH, but not cortisol, levels were higher (P <
      0.01) than those after GLU. Circulating ghrelin levels were not modified by GLU.
      On the other hand, ghrelin levels underwent a transient reduction (P < 0.01)
      after insulin-induced hypoglycaemia. CONCLUSIONS: Ghrelin does not mediate the GH
      and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not
      modified at all by glucagon and transiently decrease during the ITT. These
      findings support the assumption that ghrelin does not play a major role in the
      physiological control of somatotroph and corticotroph function.

PMID- 15163334
TI  - Erythrocyte Na/K-ATPase is increased in subjects with subclinical hypothyroidism.
AB  - OBJECTIVE: In erythrocytes of patients with overt hyperthyroidism, the number of
      ouabain-binding sites and the activity of the Na(+)/K(+)-ATPase have been
      demonstrated to be decreased, whereas the opposite is true in patients with overt
      hypothyroidism. No information has been reported on the status of the Na(+)/K(+)
      ATPase in subclinically hypothyroid (Sub Hypo) patients. DESIGN: We investigated
      the number of ouabain-binding sites and Na(+)/K(+)-ATPase activity in
      erythrocytes of chronic Sub Hypo subjects. PATIENTS AND METHODS: We measured (3)H
      ouabain-binding sites in erythrocytes from 15 patients with subclinical
      hypothyroidism, and compared with those found in 17 normal subjects (N), seven
      with overt hypothyroidism (Hypo) and 10 with overt hyperthyroidism (Hyper). The
      activity of the sodium pump was assessed by measuring ouabain-sensitive (86)Rb
      uptake in a subpopulation of the same groups. RESULTS: The number of ouabain
      binding sites in Sub Hypo patients (252 +/- 17; mean +/- SEM) was significantly
      higher (P < 0.02) than in Hyper (135 +/- 12) and N (203 +/- 10) groups, whereas
      it was not significant different from Hypo (293 +/- 31). There was a positive
      correlation between the number of ouabain-binding sites and TSH concentrations (P
      < 0.002) when Sub Hypo and N groups were considered together. There was a
      negative correlation between the number of ouabain-binding sites and free
      thyroxine (FT4; P < 0.0001) and free triiodothyronine (FT3) concentrations (P <
      0.001) when all subjects were considered. Ouabain-sensitive (86)Rb uptake
      (picomoles (86)Rb/h 10(6) cells) in Sub Hypo was significantly higher (4.2 +/-
      0.5) when compared with N (2.5 +/- 0.2, P < 0.01) and Hyper (2.5 +/- 0.5, P <
      0.02). CONCLUSIONS: Erythrocytes of subclinically hypothyroid patients show a
      significant increase in the number of ouabain-binding sites and in ouabain
      sensitive (86)Rb uptake. The state of erythrocyte Na(+)/K(+)-ATPase may therefore
      represent a biochemical marker of subclinical hypothyroidism.

PMID- 15163335
TI  - Premature birth and low birth weight associated with nonautoimmune
      hyperthyroidism due to an activating thyrotropin receptor gene mutation.
AB  - OBJECTIVE: Nonautoimmune hyperthyroidism (NAH), a rare autosomal dominantly
      inherited condition characterized by nonremitting thyrotoxicosis and the absence
      of features of autoimmune thyrotoxicosis, can result from activating germline
      mutations in the thyrotropin receptor (TSHR) gene. We report clinical and genetic
      features of a new family with NAH, and highlight that premature delivery and low
      birth weight are important characteristics of this condition. PATIENTS AND
      METHODS: Thyrotoxicosis was diagnosed in two children at the ages 20 months and 4
      years and in their father at the age of 9 years. Both children were born
      prematurely by Caesarian section at 33 and 30 weeks following early rupture of
      the membranes. Their birth weights were 1750 g (27th centile) and 790 g (< 3rd
      centile), respectively. Mutation analysis of the TSHR gene was performed in both
      children and their parents by direct DNA sequencing. RESULTS: A heterozygous
      germline mutation of the TSHR gene resulting in the substitution of serine (AGC)
      by asparagine (AAC) at codon 505 (S505N) was found, which co-segregated with
      thyrotoxicosis in the family. A review of all previously reported cases of NAH
      due to an activating TSHR germline mutation showed that the mean duration of
      gestation in these patients was significantly lower than in patients with
      inactivating TSHR mutations causing congenital hypothyroidism (35.8 weeks vs.
      39.4 weeks, P = 0.003). In addition, the mean birth weight in patients with
      activating TSHR mutations was lower than in patients with inactivating TSHR
      mutations (2338 g vs. 3470 g, P = 0.004). CONCLUSIONS: Premature delivery and low
      birth weight are consistent features of NAH due to activating TSHR germline
      mutations. This suggests a possible role for the fetal thyroid axis in the
      regulation of the timing of delivery and possibly fetal growth.

PMID- 15163336
TI  - Ultrasonographic screening for detection of thyroid cancer in patients with
      Graves' disease.
AB  - OBJECTIVE: We prospectively screened consecutive patients with Graves'
      hyperthyroidism by ultrasonography (USG), regardless of presence of palpable
      nodules, and evaluated patients with nodule(s) by fine-needle aspiration (FNA)
      and by resulting surgery to define the prevalence of thyroid cancer in patients
      with Graves' disease. METHODS: Two hundred and forty-five consecutive Graves'
      disease patients without prior thyroid surgery or radio-iodine treatment were
      enrolled at Asan Medical Centre endocrinology clinic. All patients with nodule(s)
      of 5 mm or greater were reviewed for evaluation by FNA, and of these 90.0% (n =
      62) underwent FNA. All patients with suspicious/malignant cytology or those with
      positive immunostaining with GAL-3 antibody underwent surgery. RESULTS: Among 245
      patients, thyroid nodule(s) were detected in 35.1% (86/245) by USG. Nodule
      prevalence significantly increased according to age, which was the only
      significant variable predicting the presence of nodule(s) in logistic regression
      analysis. Among patients with thyroid nodule(s), 69 patients had nodule(s) of 5
      mm or greater in size, and 62 cases of them (90.0%) underwent FNA. In eight
      patients, thyroid cancers were histologically confirmed (all papillary thyroid
      cancers), so the prevalence of thyroid cancer was at least 3.3% (8/245) in
      Graves' patients. Of eight patients with thyroid cancer, only one case was
      detected by palpation and the other seven patients were detected only by USG. In
      pathologic examination, mean size of tumour was 10.0 +/- 6.7 mm (5-25 mm), three
      cases had extrathyroidal extension (37.5%), four cases had cervical node
      metastasis (50.0%) and one case had multifocal tumour (12.5%). Thus, five of
      eight patients had locally advanced cancers (pT4 or pN1 lesion), but none had
      distant metastasis. Prevalence of thyroid cancers in Graves' disease tended to be
      higher in patients of 45 years or greater than younger patients (6.7%vs. 1.3%, P
      = 0.05), and that of the locally advanced cancers was significantly higher in
      older patients (5.6%vs. 0%, P < 0.05). Older age of the patient was the only
      significant factor predicting the presence of locally advanced thyroid cancers
      regardless of duration/severity of hyperthyroidism, goitre size, or of TBII
      activity. CONCLUSIONS: The prevalence of thyroid cancer in Graves' patients was
      at least 3.3% in this prospective analysis; most of them were micropapillary
      thyroid cancers. Stimulating TSHR antibodies seems not to induce nodule/cancer
      formation and not to change biologic behaviour of thyroid cancers in Graves'
      patients. Graves' patients of 45 years of age or above are more likely to harbour
      locally advanced thyroid cancers than younger patients, regardless of duration or
      severity of hyperthyroidism, goitre size, or of TBII activity.

PMID- 15163337
TI  - Comparison of practical methods for urinary glycosaminoglycans and serum
      hyaluronan with clinical activity scores in patients with Graves' ophthalmopathy.
AB  - OBJECTIVE: Immunosuppressive treatment of Graves' opthalmopathy (GO) should be
      restricted to patients with active eye disease, but assessing disease activity is
      difficult. Several methods to evaluate GO activity have been introduced, but none
      of them is satisfactory. Glycosaminoglycans (GAGs) are complex polysaccharides
      that participate on the pathogenesis of GO and attempts to correlate its local
      increase to urinary GAGs (uGAGs) or serum hyaluronan (sHA) have been made, but
      the available techniques are labourious, time-consuming and difficult for routine
      use. The aim of the present study is to develop practical and simple methods for
      uGAGs and sHA and compare them to the activity and severity of thyroid-associated
      ophthalmopathy. DESIGN, PATIENTS AND MEASUREMENTS: We developed a
      microelectrophoresis technique for uGAGs and a fluoroassay for sHA and assessed
      each in 152 patients with Graves' disease, 25 without GO and 127 with GO,
      classified according to the Clinical Activity Score (CAS). All patients had been
      euthyroid for > 2 months. RESULTS: Patients with inactive disease (CAS = 2, n =
      100) had uGAGs (4.2 +/- 1.3 micro g/mg/creatinine) and sHA (11.1 +/- 7.2 micro
      g/l) that did not differ from normal subjects (3.1 +/- 1.1 micro g/mg/creatinine,
      n = 138 and 13.9 +/- 9.6 micro g/l, n = 395). In contrast, patients with active
      eye disease (CAS = 3, n = 27) had uGAGs (8.4 +/- 2.7 micro g/mg/creatinine) and
      sHA (32.3 +/- 17.8 micro g/l) 2-3 times higher than those patients with inactive
      eye disease. Using a cut-off of 6.1 micro g/mg creatinine for uGAGs and 20.7
      micro g/l for sHA we found, respectively, 85% and 81% sensitivity and 93% and 91%
      specificity for each test. The positive and negative predictive values were 77%
      and 96% for uGAGs and 71% and 95% for sHA. CONCLUSION: Employing these two new
      methods we have established a significant relationship between the levels of
      uGAGs and/or sHA and the clinical activity of GO. Therefore, together with CAS,
      uGAGs determination, and, to a lesser degree, sHA, would be very useful in the
      discrimination from active and inactive ocular disease and aid in deciding on the
      best therapy for GO patients.

PMID- 15163338
TI  - One-year follow-up of patients with acromegaly treated with fixed or titrated
      doses of lanreotide Autogel.
AB  - OBJECTIVE: Somatostatin analogue treatment is first-line medical therapy for
      acromegaly. This study compared the efficacy and tolerability of titrated doses
      of the long-acting somatostatin analogue preparation lanreotide Autogel with
      fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles.
      PATIENTS: Patients entering the initial study had received a diagnosis of active
      acromegaly within the previous 5 years. DESIGN: This open, comparative,
      multicentre study was a 1-year extension of a previous trial during which
      patients with acromegaly had switched from lanreotide PR 30 mg microparticles
      injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of
      three fixed doses of lanreotide Autogel (120, 90, or 60 mg every 28 days,
      respectively). In this extension study, patients continued to receive 60, 90, or
      120 mg of lanreotide Autogel by deep subcutaneous injection every 28 days for 1
      year. Doses could be titrated at entry or after four or eight injections,
      according to the GH/IGF-I response (dose increased if GH > 2.5 micro g/l, or
      decreased if GH < 1 micro g/l with normal IGF-I). MEASUREMENTS: Mean +/- SEM GH
      and IGF-I concentrations were analysed and gallbladder echography performed at
      weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance
      and side-effects were monitored throughout the study. RESULTS: In total, 130
      patients entered this extension phase. After 1 year of treatment with titrated
      doses of lanreotide Autogel, mean GH (2.4 +/- 0.2 micro g/l) and IGF-I (287 +/-
      12 micro g/l) concentrations were significantly lower than with lanreotide
      microparticles (GH, 2.8 +/- 0.2 micro g/l, P < 0.001; IGF-I, 332 +/- 15 micro
      g/l, P < 0.01) or with fixed-dose lanreotide Autogel (GH, 3.0 +/- 0.2 micro g/l,
      P < 0.001; IGF-I, 310 +/- 14 micro g/l, P = 0.02). GH hypersecretion was reduced
      to </= 2.5 micro g/l in 68% of patients with titrated-dose lanreotide Autogel
      compared with 49% with microparticles (P < 0.001) and 56% with fixed-dose
      lanreotide Autogel (P </= 0.005). In the 65 patients who did not require any dose
      titration, there was no substantial change in serum lanreotide concentration, GH
      or IGF-I levels over the 12-month study duration. Acromegaly was effectively
      controlled (GH </= 2.5 micro g/l and normalized IGF-I) in significantly more
      patients (43%) compared with microparticles (32%; P < 0.05). There was a trend
      for improved control of acromegalic symptoms with dose titration, whereas the
      incidence of gastrointestinal symptoms and local tolerance was similar with
      lanreotide Autogel and lanreotide microparticles. Gallbladder echographies showed
      new lithiasis in 8% of lanreotide Autogel patients. CONCLUSION: Dose titration of
      lanreotide Autogel improved GH and IGF-I control in patients with acromegaly
      beyond that achieved using fixed doses of lanreotide Autogel or lanreotide
      microparticles. Titrated long-term lanreotide Autogel treatment is well
      tolerated.

PMID- 15163339
TI  - Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic
      patients undergoing peritoneal dialysis and haemodialysis.
AB  - OBJECTIVE: The GH/IGF axis is altered in chronic renal failure (CRF). CRF
      patients usually show normal or high serum concentrations of GH and IGF-I,
      whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably
      increase with declining renal function. The aims of the present study were to
      quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of
      patients with CRF, and determine whether there were differences according to the
      type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD).
      DESIGN: A cross-sectional study in the setting of a dialysis unit of a general
      hospital. PATIENTS AND MEASUREMENTS: We studied 108 dialysis patients treated by
      PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54,
      31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects
      of similar age, sex and body mass index (BMI) served as the control group.
      Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were
      measured in all patients and control subjects. RESULTS: Fasting serum
      concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were
      significantly higher in dialysis patients than in subjects with normal renal
      function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6
      +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5
      micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD)
      patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and
      insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were
      significantly higher in the PD group than in the HD group. Both groups of
      dialysis patients showed significantly higher levels of insulin than healthy
      subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD,
      respectively). In both groups of dialysis patients, IGF-I correlated inversely
      with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and
      directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P =
      0.001). No correlation between insulin and IGFBP-1 was found in any of the groups
      studied. CONCLUSIONS: These findings demonstrate that adult dialysis patients
      have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with
      subjects with normal renal function. Only GH and insulin show statistically
      significant differences in relation to type of dialysis. Finally, the negative
      correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I
      and IGFBP-3 are maintained in both groups of adult dialysis patients.

PMID- 15163340
TI  - Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar
      ratio 14 : 1) is not superior to thyroxine alone to improve well-being and
      cognitive performance in hypothyroidism.
AB  - OBJECTIVES: There is evidence from recent controlled clinical studies that
      replacement therapy of hypothyroidism with T4 in combination with a small amount
      of T3 may improve the well-being of the patients. As the issue is still the
      subject of controversial discussion, our study was assigned to confirm the
      superiority of a physiological combination of thyroid hormones (absorbed molar
      ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning.
      DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4
      weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross
      over study without washout between the treatment periods was performed in 23
      hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after
      surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of
      the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of
      the respective T4 dose was substituted by T3. MEASUREMENTS: Standard hormonal
      characteristics and standardized psychological tests to quantify mood and
      cognitive performance were measured after the run-in period and at the end of
      each treatment period. In 12 subjects, the concentration-time profiles of fT3 and
      fT4 were compared after the last administration of the respective study
      medication. TSH, fT3 and fT4 were measured with immunological assays. CLINICAL
      RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady
      state hormonal, metabolic and cardiovascular characteristics except for TSH,
      which was more suppressed after T4/T3. The efficacy of replacement therapy with
      the T4/T3 combination was not different from the T4 monotherapy with regard to
      all psychological test scores describing mood and cognitive functioning of the
      patients. Mood was even significantly impaired by the T4/T3 combination in eight
      subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck
      Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026).
      PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h))
      of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8
      +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly
      correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a
      history of Graves' disease or autoimmune thyroiditis had significantly higher
      serum trough levels of fT3 whereas the fT4 concentrations were significantly
      lower in patients with a nonautoimmune background. CONCLUSION: Replacement
      therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive
      performance compared to the standard T4 monotherapy. There is even a higher risk
      of signs of subclinical hyperthyroidism associated with impaired well-being of
      the patients, which is clearly caused by significant fluctuations in the steady
      state fT3 serum concentrations.

PMID- 15163341
TI  - Altered serum profile of inhibin B, Pro-alphaC and anti-Mullerian hormone in
      prepubertal and pubertal boys with varicocele.
AB  - OBJECTIVE: Anti-Mullerian hormone (AMH) and inhibin B are reliable markers of
      Sertoli cell function. The aim of the present study was to assess the functional
      state of Sertoli cells in order to detect early changes in the testicular
      function of prepubertal and pubertal patients with untreated grade II or III
      varicocele. DESIGN AND PATIENTS: Seven prepubertal and 55 pubertal boys with
      untreated grade II or III varicocele were studied. Seven prepubertal and 43
      pubertal normal boys were considered as controls. MEASUREMENTS: Serum levels of
      gonadotrophins, testosterone, inhibin B and Pro-alphaC and AMH were determined by
      time-resolved immunofluorometric assays, radioimmunoassay (RIA) and specific
      enzyme-linked immunosorbent assays (ELISAs), respectively. RESULTS: Inhibin B and
      Pro-alphaC serum levels were higher in prepubertal patients with varicocele than
      in controls (P < 0.001). No further increment in inhibin B and Pro-alphaC levels
      was observed in pubertal patients with varicocele. Higher levels of AMH were
      found in patients in Tanner stages I, III, IV and V when compared to normal boys
      by Tanner stage (P < 0.05, P < 0.01, P < 0.01, P < 0.001, respectively). The
      direct correlation found in normal boys between inhibin B levels and LH,
      testosterone and testicular volume was not observed in patients with varicocele.
      CONCLUSIONS: The altered serum profile of gonadal hormones observed in untreated
      prepubertal and pubertal patients with varicocele may indicate an early abnormal
      regulation of the seminiferous epithelium function.

PMID- 15163342
TI  - Profound amplification of secretory-burst mass and anomalous regularity of ACTH
      secretory process in patients with Nelson's syndrome compared with Cushing's
      disease.
AB  - OBJECTIVE: As described originally, Nelson's syndrome is characterized by grossly
      elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging
      in the course of Cushing's disease after bilateral adrenalectomy. No detailed
      studies have defined whether the mechanisms directing ACTH secretion differ in
      Nelson's syndrome and untreated Cushing's disease. PATIENTS AND METHODS: To
      address this pathophysiological issue, we studied nine patients fulfilling the
      criteria of Nelson's syndrome receiving glucocorticoid and mineralocorticoid
      replacement; nine patients with untreated pituitary-dependent Cushing's disease
      and nine gender- and age-matched controls. ACTH release was appraised by
      monitoring plasma ACTH concentrations in blood samples collected every 10 min for
      24 h. ACTH secretion rates and endogenous decay were quantified by multiparameter
      deconvolution analysis. The orderliness of the ACTH release process was
      delineated by the approximate entropy (ApEn) statistic. Diurnal variation in ACTH
      secretion was appraised by cosinor analysis. RESULTS: Basal ACTH secretion was
      increased sixfold and pulsatile secretion ninefold in patients with Nelson's
      syndrome compared with Cushing's disease (P </= 0.01 and P </= 0.001,
      respectively). The increase in pulsatile secretion was due to an eightfold
      augmentation of burst mass. Event frequency was comparable in both patient groups
      (32 +/- 1 vs. 28 +/- 2 pulses/24 h), and higher than in normal controls (22 +/- 1
      pulses/24 h, P < 0.0001). Paradoxically, the consistency of subordinate patterns
      of serial ACTH release, albeit disrupted in active Cushing's disease, was normal
      in Nelson's syndrome (P = 0.014). Normal ACTH secretory-process regularity in
      Nelson's syndrome was attributable to a more reproducible (lower ApEn) succession
      of ACTH secretory-burst mass denoting more uniform amplitude evolution over 24 h
      (P = 0.007, Nelson vs. Cushing). However, the quantifiable regularity of serial
      interburst intervals (waiting times) was unexpectedly elevated in Nelson's
      syndrome (P = 0.022). Nelson patients maintained a significant diurnal rhythm in
      ACTH release, which was marked by a 15-fold greater amplitude (P = 0.0018 vs.
      Cushing's) and a 4-h acrophase (maximum) delay (P = 0.037 vs. control).
      CONCLUSION: The present detailed analyses delineate marked ACTH secretory-burst
      mass amplification and (amplitude-independent) anomalous regularity of successive
      pulse size and timing in Nelson's syndrome compared with Cushing's disease or
      controls. We postulate that the foregoing novel distinctions are due to unique
      tumoural secretory properties, concurrently required glucocorticoid replacement
      and/or hypothalamic injury associated with prior radiotherapy in Nelson's
      syndrome.

PMID- 15163343
TI  - Surgical stress-induced transient nephrogenic diabetes insipidus (NDI) associated
      with decreased Vasopressin receptor2 (AVPR2) expression linked to nonsense
      mediated mRNA decay and incomplete skewed X-inactivation in a female patient with
      a heterozygous AVPR2 mutation (c. 89-90 delAC).

PMID- 15163346
TI  - Evidence for interplay among yeast replicative DNA polymerases alpha, delta and
      epsilon from studies of exonuclease and polymerase active site mutations.
AB  - BACKGROUND: DNA polymerase epsilon (Pol epsilon) is essential for S-phase
      replication, DNA damage repair and checkpoint control in yeast. A pol2-Y831A
      mutation leading to a tyrosine to alanine change in the Pol epsilon active site
      does not cause growth defects and confers a mutator phenotype that is normally
      subtle but strong in a mismatch repair-deficient strain. Here we investigate the
      mechanism responsible for the mutator effect. RESULTS: Purified four-subunit
      Y831A Pol epsilon turns over more deoxynucleoside triphosphates to
      deoxynucleoside monophosphates than does wild-type Pol epsilon, suggesting
      altered coordination between the polymerase and exonuclease active sites. The
      pol2-Y831A mutation suppresses the mutator effect of the pol2-4 mutation in the
      exonuclease active site that abolishes proofreading by Pol epsilon, as measured
      in haploid strain with the pol2-Y831A,4 double mutation. Analysis of mutation
      rates in diploid strains reveals that the pol2-Y831A allele is recessive to pol2
      4. In addition, the mutation rates of strains with the pol2-4 mutation in
      combination with active site mutator mutations in Pol delta and Pol alpha suggest
      that Pol epsilon may proofread certain errors made by Pol alpha and Pol delta
      during replication in vivo. CONCLUSIONS: Our data suggest that Y831A replacement
      in Pol epsilon reduces replication fidelity and its participation in chromosomal
      replication, but without eliminating an additional function that is essential for
      viability. This suggests that other polymerases can substitute for certain
      functions of polymerase epsilon.

PMID- 15163347
TI  - Report of three cases that received maintenance treatment with risperidone as a
      mood stabilizer.
AB  - INTRODUCTION: The current study is a short report of 3 cases of bipolar patients.
      MATERIAL AND METHODS: Three bipolar patients were prospectively followed up. All
      were partial responders to lithium therapy alone, and unresponsive to other
      therapies (anticonvulsants, antidepressants, typical antipsychotics, various
      combinations). RESULTS: All manifested complete remission of symptoms after
      combination therapy with lithium (plasma levels above 0.8 mEq/lt) plus 1-3 mg of
      risperidone daily. The two of them are still free of symptomatology during the
      maintenance period for 28 and 38 months respectively. The third patient, after
      several months during which she was free of symptomatology discontinued lithium
      against the psychiatrist's advise and received only 3 mg of risperidone daily.
      For the next 15 months the patient was under risperidone monotherapy and free of
      symptomatology. She discontinued therapy to become pregnant, the illness recurred
      several times during pregnancy and after the delivery the patient restarted
      risperidone therapy. She was free of symptoms for the following 9 months until
      her last follow-up. DISCUSSION: The current study provides preliminary evidence
      concerning the long term efficacy of risperidone in the treatment of bipolar
      patients

PMID- 15163348
TI  - Prevalence of Chlamydia trachomatis infection among women in a Middle Eastern
      community.
AB  - BACKGROUND: Common vaginal infections that manifest in women are usually easily
      diagnosed. However, Chlamydia infection is often asymptomatic, leading to
      infertility before it is detected. If it occurs in pregnancy, it could lead to
      significant neonatal morbidity. It may also play a role with other viral
      infections for e.g. Human Papilloma Virus in the development of cervical cancer.
      The objective of this study was to determine the prevalence of Chlamydia
      infection in women undergoing screening for cervical abnormalities as a part of a
      research project in primary and secondary care institutions in the United Arab
      Emirates. METHODS: In this cross sectional study married women attending primary
      and secondary care participating in a large nationwide cervical abnormalities
      screening survey were offered Chlamydia testing using a commercially available
      test kit. This kit uses a rapid immunoassay for the direct detection of Chlamydia
      trachomatis antigen in endocervical swab specimens. As this study was performed
      in a traditional Islamic country, unmarried women were excluded from testing, as
      the management of any positive cases would create legal and social problems. All
      married women consenting to take part in the study were included irrespective of
      age. RESULTS: Of 1039 women approached over a period of eight months 919 (88.5%)
      agreed to participate. The number of women in the 16 to 19 years was small
      (0.01%) and 30% were aged over 40 years. The prevalence of Chlamydia infection in
      this study was 2.6% (95% confidence interval 1.2-3.3%), which was marginally
      higher in women screened in secondary care (p = 0.05). CONCLUSION: This is one of
      the few reports on the prevalence of Chlamydia infection in women from the Middle
      East. Due to cultural and social constraints this study excluded a large
      proportion of women aged less than 19 years of age. Hence no direct comparisons
      on prevalence could be made with studies from the West, which all included
      younger women at high risk of Chlamydia. However this study emphasizes the
      importance of cultural factors while interpreting results of studies from
      different cultures and communities.

PMID- 15163349
TI  - Cognitive function in relation with bone mass and nutrition: cross-sectional
      association in postmenopausal women.
AB  - BACKGROUND: It has been suggested that bone loss and cognitive decline are co
      occurring conditions, possibly due to their relationship with estrogen. Cognitive
      decline has been associated with various nutritional deficiencies as well. The
      purpose of this study was to determine if cognitive function is related to bone
      mineral density of various skeletal sites as well as to various dietary
      components. METHODS: Cross-sectional study with 97 healthy, Caucasian,
      postmenopausal women (59.4-85.0 years) enrolled in a larger longitudinal study,
      investigating the effects of sodium on bone mass. The subjects were divided into
      two groups based on cognition scores. Group 1 represented lower and Group 2
      higher scores on cognitive function. Bone mineral density from the whole body,
      lumbar spine, femur and forearm were measured with the Lunar DPX-MD instrument.
      Anthropometry was measured by standard methods. Cognition was assessed using the
      Mini Mental State Examination. Cumulative (over 2 years) dietary intake from 3
      day records was analyzed by Food Processor(R) (ESHA Research, Salem, OR) and
      cumulative physical activity was assessed using Allied Dunbar National Fitness
      Survey for older adults. RESULTS: Subjects' cognition scores ranged from 22-30
      (normal, 27-30), indicating all subjects had either mild or no cognitive
      impairment. Multiple Analysis of Covariance adjusted for age, height, weight,
      physical activity, alcohol, calcium, sodium and energy intake, showed a
      statistically significant association between cognition and bone mineral density
      of all measurable sites (eta2 = 0.21, P < 0.01). However, after Analysis of
      Covariance follow-up tests and Bonferroni correction, the differences for
      individual bone sites diminished, though Group 2 had higher adjusted means for
      all sites except for the femoral neck, Ward's triangle and trochanter. There was
      a positive significant association between cognition score and carbohydrate and
      potassium intake (eta2 = 0.07, P = 0.050). Group 2 did have a significantly
      higher potassium intake (P = 0.023). In multiple regression, saturated fat had a
      significant negative relationship with cognitive function. CONCLUSIONS: It
      appears mild degree of cognitive impairment may be a marker for lower bone
      mineral density as well as for a diet lower in carbohydrate and potassium intake,
      and higher in saturated fat. Consequently, older women with cognitive impairment
      may benefit of being screened for potential bone loss and poor nutrition.

PMID- 15163350
TI  - Subjective and objective evaluation of alertness and sleep quality in depressed
      patients.
AB  - BACKGROUND: The reliability of the subjective statements reports on disturbed
      night sleep and alertness in the daytime was assessed by their correlation to the
      objective indicators in patients with mild depression. METHOD: Among patients
      with depression, altogether 28 patients with insomnia were examined. Their
      answers to typical questions, as they are used during a psychiatric interview,
      were scored. In parallel, night sleep quality and alertness level in the daytime
      were objectively estimated by means of polygraphic recording. RESULTS: The
      subjective statements on the type of insomnia, the estimated time of falling
      asleep, frequent awakenings and occurrence of disturbing dreams seem to be
      unreliable. Similarly, the results were disappointing when the patients were
      asked about alertness disturbances in the daytime. An unexpected finding was the
      lack of any significant correlation to the scores obtained by means of Epworth's
      scale. Among the factors possibly influencing the patients' reports, age, sex,
      coffee intake and also chronic administration of sedatives or hypnotics showed a
      low correlation with the sleep and alertness indicators. CONCLUSION: The
      statistical evaluation indicated rather poor agreement between the subjective and
      objective items. The statistical evaluation suggested that anxiety and depression
      significantly influence reports on sleep quality and alertness disturbances in
      the daytime.

PMID- 15163351
TI  - A microsatellite linkage map of Drosophila mojavensis.
AB  - BACKGROUND: Drosophila mojavensis has been a model system for genetic studies of
      ecological adaptation and speciation. However, despite its use for over half a
      century, no linkage map has been produced for this species or its close
      relatives. RESULTS: We have developed and mapped 90 microsatellites in D.
      mojavensis, and we present a detailed recombinational linkage map of 34 of these
      microsatellites. A slight excess of repetitive sequence was observed on the X
      chromosome relative to the autosomes, and the linkage groups have a greater
      recombinational length than the homologous D. melanogaster chromosome arms. We
      also confirmed the conservation of Muller's elements in 23 sequences between D.
      melanogaster and D. mojavensis. CONCLUSIONS: The microsatellite primer sequences
      and localizations are presented here and made available to the public. This map
      will facilitate future quantitative trait locus mapping studies of phenotypes
      involved in adaptation or reproductive isolation using this species.

PMID- 15163352
TI  - Esub8: a novel tool to predict protein subcellular localizations in eukaryotic
      organisms.
AB  - BACKGROUND: Subcellular localization of a new protein sequence is very important
      and fruitful for understanding its function. As the number of new genomes has
      dramatically increased over recent years, a reliable and efficient system to
      predict protein subcellular location is urgently needed. RESULTS: Esub8 was
      developed to predict protein subcellular localizations for eukaryotic proteins
      based on amino acid composition. In this research, the proteins are classified
      into the following eight groups: chloroplast, cytoplasm, extracellular, Golgi
      apparatus, lysosome, mitochondria, nucleus and peroxisome. We know subcellular
      localization is a typical classification problem; consequently, a one-against-one
      (1-v-1) multi-class support vector machine was introduced to construct the
      classifier. Unlike previous methods, ours considers the order information of
      protein sequences by a different method. Our method is tested in three
      subcellular localization predictions for prokaryotic proteins and four
      subcellular localization predictions for eukaryotic proteins on Reinhardt's
      dataset. The results are then compared to several other methods. The total
      prediction accuracies of two tests are both 100% by a self-consistency test, and
      are 92.9% and 84.14% by the jackknife test, respectively. Esub8 also provides
      excellent results: the total prediction accuracies are 100% by a self-consistency
      test and 87% by the jackknife test. CONCLUSIONS: Our method represents a
      different approach for predicting protein subcellular localization and achieved a
      satisfactory result; furthermore, we believe Esub8 will be a useful tool for
      predicting protein subcellular localizations in eukaryotic organisms.

PMID- 15163353
TI  - Comparative genomics.

PMID- 15163354
TI  - Application of comparative genomics to the analysis of vertebrate regulatory
      elements.
AB  - Gene regulatory regions (also known as 'cis-regulatory modules') in vertebrates
      are poorly understood and annotated by comparison with protein-coding sequences.
      The short and degenerate sequences of regulatory elements and their distribution
      over large intergenic and intronic regions pose a major challenge to genomics
      scientists. Comparative genomics can be used to identify putative regulatory
      regions, and to analyse regulatory regions into their constituent transcription
      factor binding sites. There is need for high throughput assay systems to analyse
      the function of predicted vertebrate gene regulatory regions.

PMID- 15163355
TI  - 'Gotta pick a megabase or two': in silico routes to gene regulation.
AB  - A number of vertebrate genome sequences are now available in draft or high
      quality form. By comparing genomes from related species, conserved elements that
      are located outside the coding regions can be identified, many of which represent
      regulatory elements. The design of the sequence comparisons, taking into account
      the extent of the evolutionary divergence, is crucial to the outcome. Clearly,
      investigations of these conserved regulatory elements are important in
      understanding mechanisms underlying both vertebrate evolution and human disease.

PMID- 15163356
TI  - Plenty more fish in the sea: comparative and functional genomics using teleost
      models.
AB  - Biology has collaborated with evolution to create an enormous repertoire of
      animal variation. This in turn has provided experimental biologists with models
      that can be used in the lab to simulate more complex systems. Amongst the
      organisms that have been used in this way are fish, where a large number of
      species have been utilised in a variety of different ways. Fish possess the
      smallest genomes of any vertebrate, making them ideal as models for genome
      analysis and gene discovery. Fish are also easy to maintain in a laboratory
      environment and can be bred easily. Fish often have well-defined physiology and
      respond well to many experimental procedures. Finally, fish are of great economic
      importance in their own right, as one of the world's largest sources of protein.
      In this review, the relationship between fish species is examined along with the
      role of different fish models in a wide range of biological disciplines.

PMID- 15163357
TI  - Caenorhabditis elegans functional genomics: omic resonance.
AB  - The nematode Caenorhabditis elegans is widely used as a model organism for
      studying many fundamental aspects of development and cell biology, including
      processes underlying human disease. The genome of C. elegans encodes over 19,000
      protein-coding genes and hundreds of non-coding RNAs. The availability of whole
      genome sequence has facilitated the development of high throughput techniques for
      elucidating the function of individual genes and gene products. Furthermore,
      attempts can now be made to integrate these substantial functional genomics data
      collections and to understand at a global level how the flow of genomic
      information that is at the core of the central dogma leads to the development of
      a multicellular organism.

PMID- 15163358
TI  - Yeast as a model organism for studying the evolution of non-standard genetic
      codes.
AB  - During the last 30 years, a number of alterations to the standard genetic code
      have been uncovered both in prokaryotes and eukaryotic nuclear and mitochondrial
      genomes. But, the study of the evolutionary pathways and molecular mechanisms of
      codon identity redefinition has been largely ignored due to the assumption that
      non-standard genetic codes can only evolve through neutral evolutionary
      mechanisms and that they have no functional significance. The recent discovery of
      a genetic code change in the genus Candida that evolved through an ambiguous
      messenger RNA decoding mechanism is bringing that naive assumption to an abrupt
      end by showing, in a rather dramatic way, that genetic code changes have profound
      physiological and evolutionary consequences for the species that redefine codon
      identity. In this paper, the recent data on the evolution of the Candida genetic
      code are reviewed and an experimental framework based on forced evolution,
      molecular genetics and comparative and functional genomics methodologies is put
      forward for the study of non-standard genetic codes and genetic code ambiguity in
      general. Additionally, the importance of using Saccharomyces cerevisiae as a
      model organism for elucidating the evolutionary pathway of the Candida and other
      genetic code changes is emphasised.

PMID- 15163359
TI  - Transgenic mouse models of Alzheimer's disease: how useful have they been for
      therapeutic development?
AB  - Transgenic mice have been created in an attempt to generate models of human
      Alzheimer's disease, but success has been partial and unpredictable. The overall
      aim of this paper is to illustrate how genomics can be used in translational
      research, turning genetic information in the form of pathogenic mutations into
      clinically useful drugs against a major human disease. This paper will illustrate
      how genetic information allows researchers to dissect the aetiology of a disease
      and then replicate the disease in vivo through the process of transgenesis. The
      limitations of recreating a condition like Alzheimer's disease in a transgenic
      mouse, how far the mice have advanced understanding of the disease and how useful
      they have been for the development of therapeutics will then be discussed.

PMID- 15163360
TI  - Chicken genomics charts a path to the genome sequence.
AB  - In this paper, the current status of chicken genomics is reviewed. This is timely
      given the current intense activity centred on sequencing the complete genome of
      this model species. The genome project is based on a decade of map building by
      genetic linkage and cytogenetic methods, which are now being replaced by high
      resolution radiation hybrid and bacterial artificial chromosome (BAC) contig
      maps. Markers for map building have generally depended on labour-intensive
      screening procedures, but in recent years this has changed with the availability
      of almost 500,000 chicken expressed sequence tags (ESTs). These resources and
      tools will be critical in the coming months when the chicken genome sequence is
      being assembled (eg cross-checked with other maps) and annotated (eg gene
      structures based on ESTs). The future for chicken genome and biological research
      is an exciting one, through the integration of these resources. For example,
      through the proposed chicken Ensembl database, it will be possible to solve
      challenging scientific questions by exploiting the power of a chicken model. One
      area of interest is the study of developmental mechanisms and the discovery of
      regulatory networks throughout the genome. Another is the study of the molecular
      nature of quantitative genetic variation. No other animal species have been
      phenotyped and selected so intensively as agricultural animals and thus there is
      much to be learned in basic and medical biology from this research.

PMID- 15163361
TI  - Technique review: how to use RNA interference.
AB  - RNA interference (RNAi) has been rapidly adopted as a general method for
      inhibiting gene expression in most laboratory organisms. This paper discusses how
      libraries of RNAi reagents are being used to perform genome-wide reverse genetic
      screens in both model organisms and mammalian cells. Guidelines for designing
      effective small interfering RNAs and appropriate controls for mammalian RNAi
      experiments will also be discussed.

PMID- 15163362
TI  - Additional paper: computational resources for metabolomics.
AB  - Metabolomics, a comprehensive extension of traditional targeted metabolite
      analysis, has recently attracted much attention as the biological jigsaw puzzle's
      missing piece that can complement transcriptome and proteome analysis. This
      tutorial survey introduces practical web resources with special emphasis on the
      computational aspects involved in processing and navigating metabolome data. The
      introduced materials are also accessible from the author's web directory (Atomic
      Reconstruction of Metabolism or ARM).

PMID- 15163364
TI  - Back to the biology in systems biology: what can we learn from biomolecular
      networks?
AB  - Genome-scale molecular networks, including protein interaction and gene
      regulatory networks, have taken centre stage in the investigation of the
      burgeoning disciplines of systems biology and biocomplexity. What do networks
      tell us? Some see in networks simply the comprehensive, detailed description of
      all cellular pathways, others seek in networks simple, higher-order qualities
      that emerge from the collective action of the individual pathways. This paper
      discusses networks from an encompassing category of thinking that will hopefully
      help readers to bridge the gap between these polarised viewpoints. Systems
      biology so far has emphasised the characterisation of large pathway maps. Now one
      has to ask: where is the actual biology in 'systems biology'? As structures
      midway between genome and phenome, and by serving as an 'extended genotype' or an
      'elementary phenotype', molecular networks open a new window to the study of
      evolution and gene function in complex living systems. For the study of
      evolution, features in network topology offer a novel starting point for
      addressing the old debate on the relative contributions of natural selection
      versus intrinsic constraints to a particular trait. To study the function of
      genes, it is necessary not only to see them in the context of gene networks, but
      also to reach beyond describing network topology and to embrace the global
      dynamics of networks that will reveal higher-order, collective behaviour of the
      interacting genes. This will pave the way to understanding how the complexity of
      genome-wide molecular networks collapses to produce a robust whole-cell behaviour
      that manifests as tightly-regulated switching between distinct cell fates - the
      basis for multicellular life.

PMID- 15163365
TI  - Modelling the fission yeast cell cycle.
AB  - The molecular networks regulating basic physiological processes in a cell can be
      converted into mathematical equations (eg differential equations) and solved by a
      computer. The division cycle of eukaryotic cells is an important example of such
      a control system, and fission yeast is an excellent test organism for the
      computational modelling approach. The mathematical model is tested by simulating
      wild-type cells and many known cell cycle mutants. This paper describes an
      example where this approach is useful in understanding multiple rounds of DNA
      synthesis (endoreplication) in fission yeast cells that lack the main (B-type)
      mitotic cyclin, Cdc13. It is proposed that the key physiological variable driving
      progression through the cell cycle during balanced growth and division is the
      mass/DNA ratio, rather than the mass/nucleus ratio.

PMID- 15163366
TI  - Cell-free protein synthesis for proteomics.
AB  - The use of cell-free expression systems as an alternative to cell-based methods
      for protein production is greatly facilitating studies of protein functions.
      Recent improvements to cell-free systems, and the development of cell-free
      protein display and microarray technologies, have led to cell-free protein
      synthesis becoming a powerful tool for large-scale analysis of proteins. This
      paper reviews the most commonly used cell-free systems and their applications in
      proteomics.

PMID- 15163367
TI  - Identification and characterisation of imprinted genes in the mouse.
AB  - Imprinted genes are expressed specifically from one or other parental allele.
      Over 70 are now known, and about one-half of these are expressed from the
      paternal allele and one-half from the maternal allele. Most imprinted genes are
      clustered within imprinting regions of the mouse genome, regions which are
      associated with abnormal phenotypes when inherited uniparentally. Imprinted genes
      have been identified from surveys based on differential expression or
      differential methylation according to parental origin, as well as analyses of
      candidate genes, mutants and imprinted gene clusters. Many imprinted genes affect
      growth and development, and more than 25 per cent determine non-coding RNAs that
      may have a function in controlling imprinted gene expression.

PMID- 15163368
TI  - Chromatin higher order structure: opening up chromatin for transcription.
AB  - DNA packaged into chromatin is the physiologically relevant substrate for all DNA
      dependent processes inside the nuclei of eukaryotic cells. The highly compacted
      structures of DNA and histones is inherently repressive for all DNA-dependent
      processes. Active mechanisms exist to generate dynamic chromatin, which maintains
      two apparently contradictory functions: tight compaction and free accessibility
      of DNA. The dynamics of chromatin higher order folding and the influence of
      chromatin structure on transcription will be described in this paper. Chromatin
      dynamics and higher order folding may be the key regulators of not only
      transcription but of all DNA-dependent processes in the nucleus.

PMID- 15163369
TI  - Chromatin remodelling and the interaction between enhancers and promoters in the
      beta-globin locus.
AB  - The beta-globin genes are among the most studied families of tissue-specific and
      developmentally regulated genes. Even before genome-wide sequencing was a
      reality, the sequences of extensive regions of the human, rabbit and mouse beta
      globin loci were available through the individual efforts of several research
      groups. Many of the genomic approaches now being pursued in order to understand
      the control of gene expression were applied early to this gene family with
      success. Higher levels of regulation attributable to networks of transcription
      factor interaction, chromatin remodelling and enhancer-promoter communication
      remain as challenges in the post-genomic era.

PMID- 15163370
TI  - Combining different 'omics' technologies to map and validate protein-protein
      interactions in humans.
AB  - The mapping of protein-protein interactions is key to understanding biological
      processes. Many technologies have been reported to map interactions and these
      have been systematically applied in yeast. To date, the number of reported yeast
      protein interactions that have been truly validated by at least one other
      approach is low. The mapping of human protein interaction networks is even more
      complicated. Thus, it is unreasonable to try to map the human interactome;
      instead, interaction mapping in human cell lines should be focused along the
      lines of diseases or changes that can be associated with specific cells. In this
      paper, an approach for combining different 'omics' technologies to achieve
      efficient mapping and validation of protein interactions in human cell lines is
      presented.

PMID- 15163371
TI  - [Expression of a novel human interleukin-13 in E.coli and its biological activity
      assay].
AB  - AIM: To express a novel Gln98-deleted human interleukin-13 in E.coli. METHODS:
      Total RNA was isolated from Jurkat cells costimulated with PHA and ConA. A 358 bp
      specific DNA fragment encoding hIL-13 was amplified by semi-nested RT-PCR. DNA
      sequencing showed that the target DNA was a Gln98-deleted novel splicing of hIL
      13. This hIL-13 cDNA and plasmid pBV220 were ligated at BamH I and EcoR I sites
      to construct the expression vector. After transforming E.coli strain DH5alpha,
      the expression of the novel splicing hIL-13 gene was induced by shifting culture
      temperature from 30 degrees Celsius to 42 degrees Celsius. The expression product
      was then purified by chromatography on Sepharcryl-200 gel column, and the
      bioactivity was detected by MTT colorimetry on the growth of TF-1 cell line.
      RESULTS: The novel rhIL-13 was expressed in the form of inclusion bodies. After
      purification and renaturation, the specific activity of the novel rhIL-13 was
      1.6x10(6) IU/mg. CONCLUSION: The novel rhIL-13 with biological activity has been
      obtained, which lays the foundation for treating cancer and septicemia by the
      cytokine in future.

PMID- 15163372
TI  - [Effect of the two types of TNF-alpha on the biological functions of monocytic
      cell line U937].
AB  - AIM: To compare the effect of the two types of TNF-alpha, transmembrane TNF-alpha
      (TM-TNF-alpha) and secreted TNF-alpha (sTNF-alpha) on the biological functions of
      monocytic cell line U937 so as to explore the role of TM-TNF-alpha in
      inflammation. METHODS: Effect of the two types of TNF-alpha on the functions of
      U937 cells, such as phagocytosis, accumulation of cytokines' mRNA, the level of
      cytoplasmic IkappaB-alpha and expression of ICAM-1, was compared by phagocytosis,
      RT-PCR, Western blot and FACS. RESULTS: sTNF-alpha was found to be able to
      promote markedly phagocytosis by monocytic U937 cells, enhance the mRNA
      accumulation of cytokines, such as TNF-alpha, IL-1beta and IL-8 mRNA, induce the
      degradation of IkappaB-alpha and the expression of adhesion molecule ICAM-1;
      while TM-TNF-alpha was shown to have no effect on the functions above of U937
      cells. Furthermore, it seemed TM-TNF-alpha did not have a synergic action with
      sTNF-alpha when U937 cells was treated with both types of TNF-alpha. CONCLUSION:
      The data above shows that sTNF-alpha can activate U937 cells, while TM-TNF-alpha
      has no influence. It suggests that the two types of TNF-alpha may play the
      different role in inflammation.

PMID- 15163373
TI  - [Screening of TNF-alpha mimotopes from c7c phage display peptide library].
AB  - AIM: To acquire oligo-peptides mimicking TNF-alpha epitopes. METHODS: The TNF
      alpha mimotopes were screened from c7c phage display peptide library by using
      neutralizing mAb J1D9 against TNF-alpha, and positive clones were identified by
      sandwich ELISA. RESULTS: 9 out of 20 phage clones were identified as positive
      clones which can bind to mAb J1D9. The deduced amino acid sequence analysis
      showed three different sequences: c-RRPAQSG-c, c-NKHNRKI-c and c-RGMSRKI-c.
      CONCLUSION: All of the three peptides obtained can mimic the epitopes of TNF
      alpha and bind to mAb J1D9.

PMID- 15163374
TI  - [The cloning of mouse FasL gene and expression in chondrocytes].
AB  - AIM: To clone mFasL cDNA, then insert it into retrovirus expression system
      pLNCX(2), and express mFasL cDNA in chondrocytes to study its function. METHODS:
      RT-PCR was applied to amplify mFasL cDNA from the total RNA of activated mouse
      spleen lymphocytes. The cDNA was inserted into a T-cloning vector, then subcloned
      into pLNCX(2). After transfection of chondrocytes, expression of FasL cDNA was
      detected by FACS, and activity of expressed product was analyzed by single mixed
      lymphocyte reaction(SMLC). RESULTS: mFasL cDNA fragment of 0.855 kb was
      successfully cloned and verified by sequencing. The transfection efficiency of
      mFasL cDNA in chondrocytes determined by FACS was 60.64%. Expressed product could
      evidently inhibit SMLC of allogeneic lymphocytes. It's stimulating index (SI)
      reduced to 11.71% as compare with the untransfected chondrocytes. CONCLUSION:
      Cloned recombinant pLNCX(2)-FasL can effectively express mFasL in chondrocytes,
      and can evidently inhibit SMLC of allogeneic lymphocytes.

PMID- 15163376
TI  - [Construction of the prokaryotic expression vector of MTB lhp gene and its
      expression].
AB  - AIM: To construct prokaryotic expression vector carrying lhp gene and express it
      in E.coli. METHODS: The MTB lhp gene was amplified by PCR and then cloned into
      plasmid pQE30. After sequencing, the gene was cloned into plasmid pET32a(+) to
      construct recombinant prokaryotic expression vectors pQE30-CFP10 and pET32a(+)
      CFP10. RESULTS: After transformation of the E.coli and induction with 1 mmol/L of
      IPTG, no additional protein was expressed in pQE30-CFP10 system, but recombinant
      target protein with M(r) 20 000 or so was expressed in pET32a(+)-CFP10 system,
      and the expressed protein was maximum when induced with IPTG for 4 h. The
      expressed protein existed in cytoplasm in soluble form and amounted to 38% of
      total protein of E.coli. Western blot analysis showed that the protein had good
      antigenicity. The purity of the protein purified through the Ni-NTA resin reached
      93%. CONCLUSION: The prokaryotic expression vector pET32a(+)-CFP10 was
      constructed successfully and the rCFP10 protein was obtained, which laid the
      foundation for application of the rCFP10.

PMID- 15163375
TI  - [Construction and expression of retroviral vector containing bone morphogenetic
      protein-7].
AB  - AIM: To achieve stable and long-term expression of BMP-7 gene in bone marrow stem
      cells (BMSCs). METHODS: Retrovirus expression vector containing BMP-7 gene was
      constructed and transfected into packaging cells PT67. After puromycin selection
      and cells cloning, cell clones producing high level of recombinant virus were
      obtained. The viruses were used to infect directly BMSCs and the expression of
      BMP-7 gene in BMSCs was analyzed by immunohistochemical staining. RESULTS:
      Retrovirus vector containing BMP-7 gene was successfully reconstructed and BMP-7
      was expressed in the BMSCs.The transfection rates was about 30%-40%. CONCLUSION:
      The construction of recombinant retrovirus vector containing BMP-7 gene can
      provide a reliable tool for the formation of bone or cartilage seed cells in the
      research of tissue engineering.

PMID- 15163377
TI  - [Establishment of an attenuated salmonella typhimurium vaccine strain SL3261
      expressing Hp-NAP gene].
AB  - AIM: To develop an attenuated salmonella typhimurium vaccine strain SL3261
      expressing Helicobacter pylori neutrophile activation protein(Hp-NAP). METHODS:
      The Hp-NAP gene was amplified by PCR and was cloned into prokaryotic expression
      plasmid pTrc99A to construct recombinant plasmid pTrc99A-NAP. After the pTrc99A
      NAP was performed successively by PCR, enzyme digestion analysis and sequencing
      the homology was compared between the cloned Hp-NAP gene and related genes in
      GenBank. The vaccine strain SL3261 was transformed by pTrc99A-NAP. After
      cultivation, positive colonies were picked out and the plasmid was amplified by
      PCR and enzyme digestion analysis again. The expression of Hp-NAP protein in the
      SL3261 bacteria was proved by SDS-PAGE and thin layer scanning. RESULTS:
      Sequencing and homologous analysis showed that the homology between the cloned Hp
      NAP gene and related genes in GenBank reached 98% for their nucleotide and
      deduced amino acid sequences. The expression of Hp-NAP protein could be detected
      in the culture fluid of SL3261 bacteria. Relative molecular mass (M(r)) of
      expression product was about 15 000, and expression amount accounted for 37.5% of
      total bacterial protein. CONCLUSION: An attenuated salmonella typhimurium vaccine
      strain SL3261 has been established successfully, which lays the foundation for
      further developing oral HP vaccine.

PMID- 15163378
TI  - [Site-specific mutagenesis of murine anti-human TNF-alpha Fab gene and its
      expression in E.coli].
AB  - AIM: To make the gene encoding murine anti-human TNF-alpha (hTNF-alpha) Fab
      fragment humanized construction and get its soluble expression products. METHODS:
      One-step opposite direction PCR method was applied to make the genes of heavy and
      light chain's variable region of murine antibody site-specific mutagenesis
      respectively. The mutant genes were cloned into vector pComb3H and induced to
      express through IPTG. RESULTS: It was succeeded that three point mutations were
      introduced into murine anti-hTNF-alpha monoclonal antibody, involving the
      replacement of Ser88 with Ala in heavy chain variable region(V (H)) and Glu17 and
      Lys18 with Asp and Arg, respectively in light chain variable region(V(L)), and
      that humanized Fab expression vector was constructed. It was confirmed that Fab
      fragments expressed in supernatant by Western-blot. CONCLUSION: We get soluble
      expression products of humanized Fab, which provides a sound basis for future
      research on its activity and purification.

PMID- 15163379
TI  - [Construction and Identification of DNA vaccine containing chimeric gene gag
      gp120 of HIV-1].
AB  - AIM: To construct DNA vaccine expression plasmid containing the chimeric gene gag
      gp120 of HIV-1. METHODS: The recombinant eukaryotic expression vector pVAXGE was
      constructed via inserting the chimeric gene gag-gp120 into the vector pVAX1. Hela
      cells had been transfected by recombinant plasmid via liposome. After 72 h, the
      transfected cells was detected by RT-PCR and analyzed by Dot-ELISA. RESULTS: The
      transcript products of target gene could be amplified from the cells transfected
      by recombinant plasmid. Dot-ELISA detection showed that the target gene was
      expressed in Hela cells. CONCLUSION: The DNA vaccine plasmid expressing chimeric
      gene gag-gp120 was successfully constructed, which lays the foundation for
      preparing DNA vaccine against HIV-1.

PMID- 15163380
TI  - [Induction of specific cytotoxic T lymphocytes and humoral immune response by
      MUC1 DNA vaccine in mice].
AB  - AIM: To observe the specific cytotoxic T lymphocyte and humoral immune response
      induced by MUC1 DNA inmunization in mice. METHODS: Female BALB/c mice were
      immunized intramuscularly with 100 microg pcDNA3.1-MUC1 3 times at intervals of 3
      weeks. Three weeks after the last immunization, tumor challenge experiments were
      performed by inoculation of MUC1 positive breast cancer cell line EMT6. Both
      humoral immune response and CTL-specific cytotoxicity were detected by
      immunohistochemical staining and (51)Cr release assay, respectively. RESULTS: The
      cytotoxicity of MUC1-specific CTLs to EMT6 target cells showed that the cytotoxic
      effect was different at various ratio of effector cells to target cells. At
      ratios of 100:1, 50:1, 25:1 and 12.5:1, the specific lysis in MUC1cDNA group
      reached 54.1%, 39.8%, 26.4% and 20.1%, while two control groups 13.2%, 10%, 8.2%,
      7.2% and 11.7%, 9.8%, 7.7%, 7.0%, respectively. The former was markedly higher
      than the two latters(P<0.01). MUC1 expression was exhibited to be positive in
      breast cancer tissue by immunohistochemical staining with BALB/c mouse sera
      against MUC1 cDNA. There was only 40% tumorigenic rate in MUC1 cDNA immunized
      group, while there 100% in pcDNA3.1(+) and NS control groups. There was a
      significant difference between MUC1 cDNA group and control groups (P<0.05).
      CONCLUSION: Specific CTLs and antibody prodution are elicited by MUC1 DNA
      inmunization. MUC1 cDNA inmunization partly inhibit the growth of implanted tumor
      in mice.

PMID- 15163381
TI  - [The effect of BCG on airway inflammatory reaction of experimental asthma mice].
AB  - AIM: To explore in-vivo regulation of T cells in pulmonary tissues of
      ovalbumin(OVA)-sensitized mice by BCG and its effect on airway inflammatory
      reaction. METHODS: Thirty BALB/c mice (male and female, 6 to 8 weeks of age) were
      divided into 3 groups. For the mice of first group, aerosol OVA was inhaled daily
      for 20 minutes once for 10 days running, so as to establish a OVA-sensitized
      mouse model. In the mice of second group, aerosol normal solution was inhaled
      according to the time and frequency of the first group. In the third group, the
      mice were intradermally injected with BCG of 0.04 to 0.06 mg on 10 and 14 days
      before OVA sensitization, respectively, and then aerosol purified protein
      derivative (PPD) was inhaled to the mice on 6 days after OVA sensitization. The
      changes in the number of CD4(+), CD8(+) and IFN-gamma(+) T cells in the
      inflammatory tissues and changes in the inflammatory cells in the inflammatory
      tissues and broncho-alveolar lavage fluid (BALF) were detected by SABC immuno
      histochemical staining. RESULTS: The number of CD4(+) T cells significantly
      increased in the pulmonary tissues of OVA-sensitized mice, which mainly was the
      increased number of CD4(+)/IFN-gamma(-) T cells, While the number of CD8(+) T
      cells had no notable variation, thus the ratio of CD4(+)/IFN-gamma(+) T cells
      descended. After BCG treatment, the number of CD8(+) T cells markedly increased,
      so the ratio of CD4(+)/ IFN-gamma(+) T cells variously rose, whereas the number
      of inflammatory cells decreased in BALF. CONCLUSION: BCG can upregulate the
      number of Th1 cells and lighten the airway inflammatory reaction of experimental
      asthma mice.

PMID- 15163382
TI  - [Expressions of TNF-alpha and IL-1beta in human ischemic brain tissues].
AB  - AIM: To detect the expression of TNF-alpha and IL-1beta in human cerebral
      ischemic tissues. METHODS: 13 cerebral specimens from patients died of cerebral
      infarction were divided into three groups, <2 d, 3-5 d, and >5d, according to the
      lasting time of infarctions. The expression of TNF-alpha and IL-1beta in the
      cerebral ischemic tissues were examined by immnohistochemical staining. The
      contralateral tissues were employed as controls. RESULTS: The expression of TNF
      alpha and IL-1beta in the cerebral ischemic tissues were significant higher than
      those in the contralateral tissues. The focal distribution of the TNF-alpha(+)
      and IL-1beta(+) cells was identical with the ischemic area. The expression of IL
      1beta and TNF-alpha peaked at the 3rd to 5th and 2nd day after ichemia,
      respectively. There were no significant difference between the ischemic and
      contralateral brains at the 5th day after ischemia for the expression of TNF
      alpha and IL-1beta. CONCLUSION: Our results showed the expression of TNF-alpha
      and IL-1beta in human strok of infarction were similar to those in animal
      experiments. It is suggested that TNF-alpha and IL-1beta are involved in cerebral
      ischemic injury, which will be helpful for developing clinically a novel therapy
      aiming at cerebral ischemic injury.

PMID- 15163383
TI  - [The construction and expression of a hepatocellular carcinoma-specific
      superantigen SEA (D227A) expression vector].
AB  - AIM: To construct the superantigen SEA (D227A) expression vector modulated by cis
      acting element of AFP and express it specifically on AFP(+) hepatocellular
      carcinoma (HCC) cells. METHODS: The enhancer and promoter of AFP gene, SEA
      (D227A) cDNA and linker-CD80tm were amplified by PCR. The gene segments mentioned
      above were cloned into the multiple cloning sites of retrovirus vector pLXSN to
      construct an attenuated superantigen expression vector pLXSN-SEA (D227A)-linker
      CD80tm modulated by cis-acting element of AFP gene. AFP(+) or AFP(-) HCCs were
      transfected by the superantigen expression vector through lipofectamine
      mediation. SEA expression was detected by RT-PCR and indirect immunofluorescence
      staining. RESULTS: Promoter, enhancer, SEA (D227A) and linker-CD80tm had been
      successfully cloned into the multiple cloning site of retrovirus vector pLXSN RT
      PCR and indirect immunofluorescence assay were used to prove that SEA (D227A)
      could specifically express in the AFP(+) HCCs. CONCLUSION: The successful
      construction and expression of hepatocellular carcinoma-specific superantigen SEA
      (D227A) gene expression vector lay the foundation for enhancing immunotherapy of
      hepatocellular carcinoma.

PMID- 15163385
TI  - [Effects of Shenqi compound recipe on cell cycle and apoptosis of ascites
      inducible hepatocarcinoma cell line H22].
AB  - AIM: To observe the effects of Shenqi compound recipe (SQ) on cell cycle and
      apoptosis of hepatocarcinoma cell line H22 in-vitro and in-vivo. METHODS: BALB/c
      mice bearing tumors were perfused with SQ for 10 days running. And then cytotoxic
      activity of mouse NK cells and macrophages and variation of cell cycle of H22
      cells were observed. Inhibition of H22 cell proliferation and induction of the
      their apoptosis by SQ were analyzed by flow cytometry. RESULTS: The tumor-suppre
      ssive rate of SQ was 65.68%. SQ could make H22 cells arrested at the S phase and
      induce their apoptosis. CONCLUSION: SQ has significant anti-tumor effect both in
      vitro and in-vivo. Its mechanism may be related to blocking of cell cycle and
      inducing apoptosis of H22 cells.

PMID- 15163384
TI  - [Induction of apoptosis of HepG2 cells by NDRG2].
AB  - AIM: To explore the induction of HepG2 cells by NDRG2 gene. METHODS: Human NDRG2
      gene was obtained by RT-PCR. Sequence analysis proved that sequence of NDRG2 gene
      was correct. Then the gene was inserted into the eukaryotic expression vector
      pIRES2-EGFP and transfected into NDRG2 gene-negative HepG2 cells. The changes of
      cell morphology and structure were observed under light, fluorescence and
      transmission electron microscope, respectively. The variation of cell cycle was
      detected by flow cytometry. RESULTS: The NDRG2 gene had been obtained and its
      expression vector was constructed successfully. The NDRG2 gene-transfected HepG2
      cells were shown a bad condition, structure damage, and a great number of died
      cells. The expression of target gene in cytoplasm of HepG2 cells was seen under
      fluorescence microscope. Flow cytometry analysis showed G1 phase arrest and
      apoptosis peak appeared.The typical manifestation of cell apoptosis could be
      observed under transmission electron microscope. CONCLUSION: NDRG2 gene can
      arrest HepG2 cell proliferation and induce their apoptosis.

PMID- 15163386
TI  - [Survey research of serum anti-influenza virus antibody levels in Chinese young
      people during 1997-2000].
AB  - AIM: To survery the levels of serum anti-influenza virus antibodies and variable
      extent of the virus in the young people. METHODS: The levels of anti-influenza
      virus antibody in the serum samples collected from 3 000 young people of eight
      different areas in China in spring and autumn per year during 1997-2000 were
      detected by microhemagglutination inhibition test. RESULTS: The antibody levels
      of the young people fluctuated between the spring and autumn per year. The levels
      of antibody against type A3 virus (H3N2) preserved high from 1999-2000, while the
      level of antibody to type A1 (H1N1) decreased from 1998 to 2000 and the
      percentages of people susceptible to this type rose from 15% to 75%. CONCLUSION:
      The epidemic of H3N2, H1N1 viruses and influenza virus type has occurred at some
      areas in China. Significant variation appeared in H1N1 virus, while the variation
      of H3N2 virus will be expected.

PMID- 15163387
TI  - [Effects of perindopril on plasma soluble TRAIL and receptor soluble DR5 in
      patients with congestive heart failure].
AB  - AIM: To explore the levels of soluble TRAIL and DR5 in plasma of patients with
      congestive heart failure (CHF) and the effects of perindopril. METHODS: 58 CHF
      patients were randomly divided into two groups, namely perindopril treatment
      group (30 cases) and routine treatment group (28 cases). The levels of sTRAIL and
      sDR5 in plasma of 30 CHF patients treated with perindopril, 28 CHF patients
      treated with routine method before and after treatment and 20 healthy persons
      were detected by ELISA. RESULTS: (1)The mean levels of sTRAIL in plasma of 58 CHF
      patients and 20 healthy persons were (1.43+/-0.47) microg/L and (0.93+/-0.12)
      microg/L, respectively, the comparison between the patients and healthy persons
      had no notable difference (P>0.05), suggesting that plasma sTRAIL level had no
      significant relation to injured level of cardiac function. As for sDR5 level, the
      mean level in plasma of 58 CHF patients was (39.67+/-6.78) ng/L, this value was
      significantly higher than that of healthy control group, and the level of sDR5
      was increased with the injured level of cardic function.(2)The plasma levels of
      sTRAIL in both perindopril group and conventional treatment group decreased after
      treatment, but there was no significant difference. The mean levels of plasma
      sDR5 in perindopril group were (31.23+/-10.16 ) ng/L and (8.50+/-2.14) ng/L; the
      levels in conventional group (48.81+/-8.74) ng/L and (26.64+/-6.27) ng/L,
      respectively, the perindopril group was lower than the conventional group
      descending rates were 72.7% and 45.3% respectively.(3)The level of plasma sDR5 in
      CHF patients resulting from hypertensive cardiopathy was much higher than that in
      CHF patients resulting from any other etiological factors. CONCLUSION: DR5 may
      play an important role in the occurrence and progress of myocardium apoptosis of
      CHF patients. Perindopril can down-regulate the level of plasma sDR5, therefore,
      it may have the great effect on retarding course of ventricular remodeling,
      protecting and improving cardial function of CHF patients.

PMID- 15163388
TI  - [Effects of LFA-1 costimulation on proliferation and IgG production of PBMCs from
      lupus nephritis patients].
AB  - AIM: To study the effect of lymphocyte function associated antigen-1(LFA-1)
      costimulation on proliferation and immunoglobin production of peripheral blood
      mononuclear cells(PBMCs) form lupus nephritis(LN) patients. METHODS: 29 LN
      patients were enrolled in this study, and 12 healthy persons served as control.
      PBMCs from LN patients and healthy persons were obtained by Ficoll density
      gradient centrifugation, and cell proliferation was detected by (3)H-TdR
      incorporation. IgG content in cultural supermatant was detected by ELISA.
      RESULTS: Stimulation of anti-CD3 mAb alone could enhance the proliferation and
      IgG production of PBMCs from 29 LN patients,while the effects on PBMCs from
      patients in active phase were stronger than those from the patients in the
      inactive phase (P<0.01). But anti-CD3 mAb had no influenence on PBMCs from
      healthy persons.The costimulation of anti-CD3 mAb and LFA-1 could increase
      proliferation and IgG production of PBMCs from LN patients and healthy persons.
      The effects of this costimulation decreased in turn from active and inactive LN
      patients to normal persons (P<0.01). The costimulant effects of LFA-1 was
      inhibited by anti-LFA-1 mAb. CONCLUSION: The effects of enhancing PBMC
      proliferation and IgG production by LFA-1 may be a mechanism of LN pathogenesis.

PMID- 15163389
TI  - [The effect of continuous high-volume hemofiltration therapy on TNF-alpha of
      pancreatitis patients complicated with acute renal function failure].
AB  - AIM: To explore the role of continuous high-volume renal replacement therapy(HV
      CRRT) in serum TNF-alpha removal. METHODS: 13 panceatitis patients complicated
      with acute renal failure were treated by continuous venovenous hemofiltration
      (CVVH), and they were divided into two groups according to the substitution rate
      during CVVH. The substitution rate of group I (8 cases) was 2 L/h, the that of
      group II(5 cases) was 4 L/h. 1ml blood samples were taken from the post-filter at
      0,1,2,3,6 and 24 h after CRRT, respectively. The TNF-alpha level produced from
      endotoxin-induced periphral blood mononuclear cells (PBMCs) was detected by
      ELISA. Ultrafiltrate samples were co-incubated with donor's whole blood
      containing ET so as to detect suppression activity of ultrafiltrate. RESULTS:
      Production of TNF-alpha by ET-induced PBMCs was significantly suppressed in group
      I and II. During CVVH treatment, suppressed ET-induced TNF-alpha production
      increased variously in the first 3 h, and then decreased gradually. In contrast,
      the increased levels of ET-induced TNF-alpha production in group II were higher
      than that in group I, and maintained a higher level until 24 h after CVVH
      therapy. The ultrafiltrate from group I had no suppressing activity, but the
      ultrafiltrate from group II suppressed ET-induced TNF-alpha production, the
      suppression rate was (15+/-6)%. CONCLUSION: HV-CRRT is more effective than
      standard CRRT in removal of inflammatory mediators. The mediators are removed
      mainly by filter membrane adsorption, and maybe partly by convection. Therefore,
      HV-CRRT with large-pore filter membranes is an effective way in removal of
      inflammatory mediators.

PMID- 15163390
TI  - [Activation effects of BCR/ABL antigen on CML T cells mediated by protein
      transduction domain].
AB  - AIM: To study the activation effect of BCR/ABL antigen on T cells from CML
      patients mediated by protein transduction domain (PTD). METHODS: The fused
      plasmid containing PTD gene and b3a2 bcr/abl gene of CML was constructed by
      genetic engineering technique and was expressed in E.coli. The PBMCs from CML
      patients were stimulated in-vitro with purified PTD-BCR/ABL antigen and then
      expression of the activation antigen CD25 on CD8(+) and CD4(+) T cells after
      stimulation was detected by flow cytometry (FCM). RESULTS: After stimulation with
      100 mg/L of PTD-BCR/ABL antigen (final concentration) for 4 days in-vitro, CD8(+)
      T cells were activated in 5 of 10 CML patients and CD4(+) T cells were activated
      in 2 of 10 patients. Both CD8(+) and CD4(+) T cells were activated simultaneously
      in one of them. However, neither CD4(+) nor CD8(+) T cells was activated in
      BCR/ABL antigen stimulation group as control. CONCLUSION: Using a PTD-mediated
      antigen transduction system, exogenous BCR/ABL antigen can be transferred into
      APCs and be processed and presented onto surface of APCs to activate Ag-specific
      CD8(+) and CD4(+) T cells in-vitro. The strategy outlined in this paper may
      provide a new approach for priming Ag-specific CD8(+) and CD4(+) T cells in-vitro
      and immunotherapy of CML.

PMID- 15163391
TI  - [Preliminary observation of CXCR3 expression on peripheral blood lymphocytes from
      patients with chronic hepatitis B infection].
AB  - AIM: To explore the role of chemokine receptor CXCR3 in pathogenesis of chronic
      hepatitis B. METHODS: The expression of CXCR3 on peripheral blood lymphocytes
      from chronic hepatitis B patients with various degrees of inflammation was
      detected, and the distributions of CXCR3 on CD4(+) and CD8(+) T lymphocytes were
      also evaluated by FACS. RESULTS: As compared with healthy control, the
      percentages of CXCR3(+) lymphocytes, monocytes and CD8(+) T cells were increased
      significantly in chronic hepatitis B patients. CONCLUSION: Above data suggest
      that chemokine receptor CXCR3 may play an important role in the recruitment of
      lymphocytes, especially CTLs recruited to inflammation sites.

PMID- 15163392
TI  - [Comparative studies on the resistance of hepatitis B by Syringa extract, IFN and
      ganyanling in HepG2.2.15 cells].
AB  - AIM: To explore the effects of Syringa extract, IFN and ganyanling on the the
      survival rate of HepG2.2.15 cells and the secretion of HBsAg and HBeAg by
      HepG2.2.15 cells. METHODS: (3)H-TdR incorporation and ELISA were used to detect
      respectively the survival rate of HepG2.2.15 cells and levels of HBsAg and HBeAg
      in culture supernatant of HepG2.2.15 cells after stimulation with 3 drugs.
      RESULTS: (1)All of the three drugs decreased the survival rate of HepG2.2.15
      cells to the various extent with the increase of doses. The effect of the Syringa
      extract was between those of IFN and ganyanling. (2)All of the three drugs might
      suppress the secration of HBsAg and HbeAg by HepG2.2.15 cells in dose-dependent
      manner, while the the effect of the syringa extract was between those of IFN and
      ganyanling. CONCLUSION: The Syringa extract is an effective and low toxic anti
      hepatitis B drug.

PMID- 15163393
TI  - [Effects of altered peptide ligands (APLs) of proteolipid(136-150) on T-cell
      clone 4B.14a].
AB  - AIM: By investigating the effects of APLs of PLP(136-150) on T cell clone 4B.14a
      in-vitro and in-vivo, to determine the feasibility of APLs to prevent relapsing
      multiple sclerosis (MS) in human. METHODS: To mimic the clinic course of
      relapsing MS, SJL/J female mice were first irradiated at 450R and intravenously
      infused with 1x10(7) resting 4B.14a T cells per mouse. Then mice were immunized
      with 50 microg/mouse APL for inducing passive experiment allergic
      encephalomyelitis (EAE). The proliferation and cytokine production of 4B.14a T
      cells in response to APLs were also examined. RESULTS: Except 139A, 143A, 144A,
      145A and 148A, other APLs triggered T cells to induce passive EAE; 4B.14a T cells
      well responded to the most APLs, weakly responded to 137A, 144A and 148A, but the
      response was suppressed by 139A. CONCLUSION: The effects of some APLs on 4B.14a T
      cells are different in-vitro and in-vivo. It may be feasible to select some APLs
      to prevent relapsing MS in human.

PMID- 15163394
TI  - [Enhancement effect of IL-2 on the proliferation of cultured mammary carcinoma
      cell line Bcap-37].
AB  - AIM: To investigate the effects of IL-2 on the proliferation of human mammary
      carcinoma cell line Bcap-37 and explore its possible mechanism. METHODS:
      Enhancement effect of IL-2 on proliferation of cultured Bcap-37 cells, the IL-2
      expression on the cells, the expressions of IL-2Ralpha, beta, gamma mRNAs in the
      cells, the effect of IL-2 on DNA content at various periods of cell cycle and on
      Ca(2+) concentration in the cells were detected or observed by MTT colorimetry,
      immunohistochemical staining, RT-PCR, flow cytometry and laser scanning confocal
      microscope, respectively. RESULTS: IL-2 of 1x10(5) to 1x10(6) U/L significantly
      stimulated the proliferation of cultured Bcap-37 cells. IL-2 was secreted and IL
      2Ralpha, beta and gamma were expressed by cultured Bcap-37 cells. IL-2(1x10(5)
      U/L) increased ratio of Bcap-37 cells in G(2) and S phases and decreased the
      Ca(2+) release from Bcap-37 cells. CONCLUSION: IL-2 significantly enhance the
      proliferation of mammary carcinoma cell line Bcap-37. The enhancement effect of
      IL-2 on Bcap-37 cell proliferation is possibly related to the expression of IL-2R
      and decreased Ca(2+) concentration in the cells.

PMID- 15163395
TI  - [Preparation and preliminary identification of the monoclonal antibody to bovine
      bFGF].
AB  - AIM: To prepare mAb against bovine bFGF and identify their Ig subgroups so as to
      establish an ELISA for detection of bFGF level. METHODS: BALB/c mice were
      immunized by recombinant bovine bFGF. Hybridoma cell lines which could stably
      secret the monoclonal antibodies to bFGF were established by cell fusion
      technique, and their related characteristics were identified. In addition,
      polyclonal antibodies to bFGF were prepared by immunization of rabbits with
      bovine bFGF. The mAb and polyclonal antibodies purified through protein A
      affinity chromatography were used to develop a sandwich ELISA for detection of
      bFGF level. RESULTS: Three hybridoma cell lines which could secret the mAbs IgG 1
      to bFGF were obtained. The concentration of bFGF could be detected by sandwich
      ELISA developed with purified mAb and polyclonal antibody at nanogram level.
      CONCLUSION: mAb and polyclonal antibodies against to bovine bFGF have been
      prepared successfully, which provide powerful tool for further clinical
      application and related studies.

PMID- 15163396
TI  - [Preparation of monoclonal antibodies against morphine and preliminary
      application of its colloidal gold conjugates].
AB  - AIM: To prepare monoclonal antibodies (mAbs) against morphine. METHODS: Morphine
      was conjugated to rabbit serum albumin or bovine serum albumin, respectively and
      the BALB/c mice were immunized with the conjugated. The mAbs against morphine
      were obtained by hybridoma technique. The urine samples were detected with the
      paper chromatography based on crosslinked of the purified mAb with colloidal
      gold. RESULTS: Three mAbs against morphine were obtained and the sensitivity
      detected by paper chromatography reached to 200 microg/L. CONCLUSION: The
      successful preparation of the mAb and its colloid gold conjugates may be useful
      for field check.

PMID- 15163397
TI  - [Morphological evidence on participating in adhesive function of human umbilical
      vein endothelial cells by CD226].
AB  - AIM: To provide the morphological evidence on participating in the adhesive
      function of human umbilical vein endothelial cells by CD226. METHODS: Human
      umbilical vein endothelial cells(HUVECs) were cultured and the effect of CD226 on
      the adhesion between activated HUVEC and activated PBMC were observed by Leica
      inverted microscope and scanning electron microscope. RESULTS: Fusion protein
      CD226/Ig could block the adhesion between activated HUVECs and activated PBMC
      markedly. CONCLUSION: CD226 was a novel inducible adhesion molecule expressed on
      activated endothelial cells, which may possess important physiological and
      pathological function.

PMID- 15163398
TI  - [Purification and characterization of the fusion protein TGF-betaR II/Fc].
AB  - AIM: To express the fusion protein TGF-betaR II/Fc in large amounts by using
      recombinant Bac-TR II baculovirus expression system constructed by our laboratory
      and to purify and characterize it. Then, to verify whether the fusion protein TGF
      betaR II/Fc can be able to block the biological activity of cytokine TGF-beta1.
      METHODS: The viral titer was determined by plaque forming test. The recombinant
      baculovirus was amplified by infecting sf9 cells. The fusion protein was purified
      by FPLC using protein G column. The purified product was analyzed by SDS-PAGE and
      the amount of target protein calculated by gray scanning. Western blot and
      sandwich ELISA were used to affirm the expression of the fusion protein. MTT
      colorimetry was used to test whether the fusion protein can block the inhibition
      effect of cytokine TGF-beta1 on the growth of L929 cells. It was to verify
      whether the fusion protein can reduce the fibronectin production in L929 cells
      accelerated by TGF-beta1 by western blot. RESULTS: The titer of recombinant Bac
      TR II baculavirus in the primary culture fluid was 2x10(12) pfu/L. After
      electrophoresis, gray scanning analysis showed that the target protein accounted
      for 10 percent of the total protein. Western blot analysis and sandwich ELISA
      detection proved that the target protein has been expressed. The fusion protein
      could block the inhibitive effect of cytokine TGF-beta1 on the growth of L929
      cells and fibronectin production in L929 cells. CONCLUSION: The fusion protein
      TGF-betaR II/Fc can inhibit the biological activity of TGF-beta1 in-vitro. This
      study will be helpful to the mass production of the fusion protein, and will
      facilitate its further use in the therapy of pulmonary fibrosis.

PMID- 15163399
TI  - [Study on a new IL-12 inducing gene NAP2].
AB  - AIM: To study the function of newly cloned NF-kappaB-activating gene (NAP2) and
      its mechanism. METHEDS: Activation of NF-kappaB and IL-12 promoters as well as
      modulation of IL-12 synthesis by NAP2 in macrophages were observed by NF-kappaB
      and IL-12 luciferase reporter assay and intracellular IL-12 staining. RESULTS:
      NAP2 could activate NF-kappaB and IL-12 promoter. But IkappaBalphaDN could
      inhibit their activation. In addition, NAP2 could induce IL-12 expression in
      macrophage cell line J774. CONCLUSION: NAP2 as a newly cloned NF-kappaB
      activating gene can activate IL-12 promoter and induce IL-12 expression in
      macrophages. The data suggest that NAP2 regulates the expression of IL-12 most
      likely through its modulation of NF-kappaB transcription factor.

PMID- 15163400
TI  - [Study on immunoreaction induced by DCs loaded with hepatocarcinoma antigen
      peptide in-vitro].
AB  - AIM: To investigate the potency and antitumor effect of specific cytotoxic T
      lymphocytes induced by hepatocarcinoma antigen peptide EPVTKAEML-loaded dendritic
      cells (DCs). METHODS: The healthy donors of HLA-B7 genotype were selected by PCR
      SSP. Isolated and cultured DCs from HLA-B7 donors' spleen tissues were loaded
      with the peptide EPVTKAEML from hepatocarcinoma cell line HHCC. The specific CTL
      reaction and inhibitory effect of anti-HLA-I molecule mAb on CTL cytotoxicity
      were detected in-vitro by (51)Cr-release assay. RESULTS: 4 donors with HLA-B7
      genotype were found. Their spleen T lymphocytes could be induced to proliferate
      and differentiate into specific CTLs by DCs loaded with the peptide. Antibody
      blocking test demonstrated that the cytotoxity of CTLs was strictly limited by
      MHC-I molecule. CONCLUSION: EPVTKAEML-loaded DCs can induce efficient and
      specific antitumor immune reaction in-vitro.

PMID- 15163401
TI  - [Study on the preliminary purification and bioactivity of recombinant human TNF
      alpha mutein 471].
AB  - AIM: To purify preliminary recombinant human TNF-alpha mutein 471 and detect its
      bioactivity on the basis of the TNF-alpha mutein 471 expressed in prokaryotic
      express system. METHODS: The expression of recombinant human TNF-alpha mutein 471
      in engineering bacteria strains E.coil was induced under the condition of optimal
      fermentation and expression. After cultured E.coil cells were collected and
      broken by using an ultrasonic disintegrator, the TNF-alpha mutein 471 existed in
      the form of inclusion body was extracted and purified, and then the effects of
      denaturation and protein concentration on protein folding were examined. The
      bioactivities of wild type TNF-alpha and the TNF-alpha mutein 471 were detected
      by MTT colorimetry. RESULTS: The TNF-alpha mutein 471 was folded and polymerized
      successfully to from a trimer with bioactivity under the condition of proper
      denaturation and renaturation. The cytotoxic activity of the TNF-alpha mutein 471
      to the L929 cells was 15 times as much as wild type TNF-alpha. CONCLUSION: The
      TNF-alpha mutein 471 expressed in prokaryotic expression system possesses
      significantly bioactivity after renaturation, which lays the foundation for
      further animal experiment and clinical experimental researches.

PMID- 15163403
TI  - Reprogramming committed B lineage cells.
AB  - It is generally assumed that once a cell commits to a certain lineage it no
      longer can change its fate. A new study in this issue of Cell provides compelling
      evidence that committed mature B lineage cells can be reprogrammed to become
      macrophages.

PMID- 15163402
TI  - Checkpoint adaptation; molecular mechanisms uncovered.
AB  - Adaptation to the DNA damage checkpoint is a phenomenon long thought to be
      confined to the unicellular world. A new report in this issue of Cell by suggests
      the presence of a checkpoint adaptation pathway in Xenopus egg extracts that
      displays interesting molecular parallels to adaptation in yeast.

PMID- 15163404
TI  - Class II MHC: sweetening the peptide only diet?
AB  - MHC molecules typically bind peptides to create ligands for the T cell antigen
      receptor. In this issue of Cell, report an unexpected association of class II MHC
      molecules with processed zwitterionic polysaccharides from pathogenic bacteria.
      The complexes appear to modulate the T cell dependent pathology of abscess
      formation.

PMID- 15163405
TI  - Inflammatory caspases: linking an intracellular innate immune system to
      autoinflammatory diseases.
AB  - Caspases not only play an essential role during apoptotic cell death, but a
      subfamily of them-the inflammatory caspases-are associated with immune responses
      to microbial pathogens. Activation of inflammatory caspases, such as caspase-1
      and caspase-5, occurs upon assembly of an intracellular complex, designated the
      inflammasome. This results in the cleavage and activation of the proinflammatory
      cytokines IL-1beta and IL-18. Mutations in one of the scaffold proteins of the
      inflammasome, NALP3/Cryopyrin, are associated with autoinflammatory disorders
      underscoring the importance of regulating inflammatory caspase activation.

PMID- 15163406
TI  - Adaptation of a DNA replication checkpoint response depends upon inactivation of
      Claspin by the Polo-like kinase.
AB  - The checkpoint mediator protein Claspin is essential for the ATR-dependent
      activation of Chk1 in Xenopus egg extracts containing aphidicolin-induced DNA
      replication blocks. We show that, during this checkpoint response, Claspin
      becomes phosphorylated on threonine 906 (T906), which creates a docking site for
      Plx1, the Xenopus Polo-like kinase. This interaction promotes the phosphorylation
      of Claspin on a nearby serine (S934) by Plx1. After a prolonged interphase
      arrest, aphidicolin-treated egg extracts typically undergo adaptation and enter
      into mitosis despite the presence of incompletely replicated DNA. In this
      process, Claspin dissociates from chromatin, and Chk1 undergoes inactivation. By
      contrast, aphidicolin-treated extracts containing mutants of Claspin with alanine
      substitutions at positions 906 or 934 (T906A or S934A) are unable to undergo
      adaptation. Under such adaptation-defective conditions, Claspin accumulates on
      chromatin at high levels, and Chk1 does not decrease in activity. These results
      indicate that the Plx1-dependent inactivation of Claspin results in termination
      of a DNA replication checkpoint response.

PMID- 15163407
TI  - The active site of the ribosome is composed of two layers of conserved
      nucleotides with distinct roles in peptide bond formation and peptide release.
AB  - Peptide bond formation and peptide release are catalyzed in the active site of
      the large subunit of the ribosome where universally conserved nucleotides
      surround the CCA ends of the peptidyl- and aminoacyl-tRNA substrates. Here, we
      describe the use of an affinity-tagging system for the purification of mutant
      ribosomes and analysis of four universally conserved nucleotides in the innermost
      layer of the active site: A2451, U2506, U2585, and A2602. While pre-steady-state
      kinetic analysis of the peptidyl transferase activity of the mutant ribosomes
      reveals substantially reduced rates of peptide bond formation using the minimal
      substrate puromycin, their rates of peptide bond formation are unaffected when
      the substrates are intact aminoacyl-tRNAs. These mutant ribosomes do, however,
      display substantial defects in peptide release. These results reveal a view of
      the catalytic center in which an inner shell of conserved nucleotides is pivotal
      for peptide release, while an outer shell is responsible for promoting peptide
      bond formation.

PMID- 15163408
TI  - Structure of Ero1p, source of disulfide bonds for oxidative protein folding in
      the cell.
AB  - The flavoenzyme Ero1p produces disulfide bonds for oxidative protein folding in
      the endoplasmic reticulum. Disulfides generated de novo within Ero1p are
      transferred to protein disulfide isomerase and then to substrate proteins by
      dithiol-disulfide exchange reactions. Despite this key role of Ero1p, little is
      known about the mechanism by which this enzyme catalyzes thiol oxidation. Here,
      we present the X-ray crystallographic structure of Ero1p, which reveals the
      molecular details of the catalytic center, the role of a CXXCXXC motif, and the
      spatial relationship between functionally significant cysteines and the bound
      cofactor. Remarkably, the Ero1p active site closely resembles that of the
      versatile thiol oxidase module of Erv2p, a protein with no sequence homology to
      Ero1p. Furthermore, both Ero1p and Erv2p display essential dicysteine motifs on
      mobile polypeptide segments, suggesting that shuttling electrons to a rigid
      active site using a flexible strand is a fundamental feature of disulfide
      generating flavoenzymes.

PMID- 15163409
TI  - The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to
      promotion of actin assembly.
AB  - The widespread beta-thymosin/WH2 actin binding domain has versatile regulatory
      properties in actin dynamics and motility. beta-thymosins (isolated WH2 domain)
      maintain monomeric actin in a "sequestered" nonpolymerizable form. In contrast,
      when repeated in tandem or inserted in modular proteins, the beta-thymosin/WH2
      domain promotes actin assembly at filament barbed ends, like profilin. The
      structural basis for these opposite functions is addressed using ciboulot, a
      three beta-thymosin repeat protein. Only the first repeat binds actin and
      possesses the function of ciboulot. The region that shows the strongest
      interaction with actin is an amphipathic N-terminal alpha helix, present in all
      beta-thymosin/WH2 domains, which recognizes the ATP bound actin structure and
      uses the shear motion of actin linked to ATP hydrolysis to control
      polymerization. Crystallographic ((1)H, (15)N), NMR, and mutagenetic data reveal
      that the weaker interaction of the C-terminal region of beta-thymosin/WH2 domain
      with actin accounts for the switch in function from inhibition to promotion of
      actin assembly.

PMID- 15163410
TI  - Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent
      switching from a peroxidase to a molecular chaperone function.
AB  - Although a great deal is known biochemically about peroxiredoxins (Prxs), little
      is known about their real physiological function. We show here that two cytosolic
      yeast Prxs, cPrxI and II, which display diversity in structure and apparent
      molecular weights (MW), can act alternatively as peroxidases and molecular
      chaperones. The peroxidase function predominates in the lower MW forms, whereas
      the chaperone function predominates in the higher MW complexes. Oxidative stress
      and heat shock exposure of yeasts causes the protein structures of cPrxI and II
      to shift from low MW species to high MW complexes. This triggers a peroxidase-to
      chaperone functional switch. These in vivo changes are primarily guided by the
      active peroxidase site residue, Cys(47), which serves as an efficient "H(2)O(2)
      sensor" in the cells. The chaperone function of these proteins enhances yeast
      resistance to heat shock.

PMID- 15163411
TI  - Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor
      biosynthesis at the ER.
AB  - The yeast ERI1 gene encodes a small ER-localized protein that associates in vivo
      with GTP bound Ras2 in an effector loop-dependent manner. We showed previously
      that loss of Eri1 function results in hyperactive Ras phenotypes. Here, we
      demonstrate that Eri1 is a component of the GPI-GlcNAc transferase (GPI-GnT)
      complex in the ER, which catalyzes transfer of GlcNAc from UDP-GlcNAc to an
      acceptor phosphatidylinositol, the first step in the production of GPI-anchors
      for cell surface proteins. We also show that GTP bound Ras2 associates with the
      GPI-GnT complex in vivo and inhibits its activity, indicating that yeast Ras uses
      the ER as a signaling platform from which to negatively regulate the GPI-GnT. We
      propose that diminished GPI-anchor protein production contributes to hyperactive
      Ras phenotypes.

PMID- 15163412
TI  - RNA and RNA binding proteins participate in early stages of cell spreading
      through spreading initiation centers.
AB  - Focal adhesions are specialized attachment and signaling centers that form at
      sites of cell-matrix contacts. We employed a quantitative mass spectrometry-based
      method called SILAC to identify and quantify proteins interacting in an
      attachment-dependent manner with focal adhesion proteins. Subsequent confocal
      microscopy revealed a previously undescribed structure, which we have termed a
      spreading initiation center (SIC), existing only in early stages of cell
      spreading. SICs contain focal adhesion markers, appear to be surrounded by an
      actin sheath, and, surprisingly, contain numerous RNA binding proteins, ribosomal
      RNA, and perhaps other RNAs. Interfering with the function of FUS/TLS, hnRNP K,
      and hnRNP E1 results in increased spreading. Spreading initiation centers are
      ribonucleoprotein complexes distinct from focal adhesions and demonstrate a role
      for RNA and RNA binding proteins in the initiation of cell spreading.

PMID- 15163413
TI  - Stepwise reprogramming of B cells into macrophages.
AB  - Starting with multipotent progenitors, hematopoietic lineages are specified by
      lineage-restricted transcription factors. The transcription factors that
      determine the decision between lymphoid and myeloid cell fates, and the
      underlying mechanisms, remain largely unknown. Here, we report that enforced
      expression of C/EBPalpha and C/EBPbeta in differentiated B cells leads to their
      rapid and efficient reprogramming into macrophages. C/EBPs induce these changes
      by inhibiting the B cell commitment transcription factor Pax5, leading to the
      downregulation of its target CD19, and synergizing with endogenous PU.1, an ETS
      family factor, leading to the upregulation of its target Mac-1 and other myeloid
      markers. The two processes can be uncoupled, since, in PU.1-deficient pre-B
      cells, C/EBPs induce CD19 downregulation but not Mac-1 activation. Our
      observations indicate that C/EBPalpha and beta remodel the transcription network
      of B cells into that of macrophages through a series of parallel and sequential
      changes that require endogenous PU.1.

PMID- 15163414
TI  - Polysaccharide processing and presentation by the MHCII pathway.
AB  - The adaptive immune system functions through the combined action of antigen
      presenting cells (APCs) and T cells. Specifically, class I major
      histocompatibility complex antigen presentation to CD8(+) T cells is limited to
      proteosome-generated peptides from intracellular pathogens while the class II
      (MHCII) endocytic pathway presents only proteolytic peptides from extracellular
      pathogens to CD4(+) T cells. Carbohydrates have been thought to stimulate immune
      responses independently of T cells; however, zwitterionic polysaccharides (ZPSs)
      from the capsules of some bacteria can activate CD4(+) T cells. Here we show that
      ZPSs are processed to low molecular weight carbohydrates by a nitric oxide
      mediated mechanism and presented to T cells through the MHCII endocytic pathway.
      Furthermore, these carbohydrates bind to MHCII inside APCs for presentation to T
      cells. Our observations begin to elucidate the mechanisms by which some
      carbohydrates induce important immunologic responses through T cell activation,
      suggesting a fundamental shift in the MHCII presentation paradigm.

PMID- 15163416
TI  - External quality control assessment in PCR diagnostics of dengue virus
      infections.
AB  - BACKGROUND: Increased travelling to countries endemic for dengue fever (DF)
      demands efficient laboratory diagnostics. Nucleic acid amplification techniques
      (NAT) are now frequently used for rapid diagnosis of imported viral diseases.
      Different PCR systems are available. OBJECTIVES: In order to assess the quality
      of molecular diagnostics of dengue virus infections, an external quality
      assurance (EQA) in PCR diagnostics was conducted. STUDY DESIGN: A panel of 10
      human plasma samples was prepared and spiked with dengue virus types DEN-1 to DEN
      4. In addition, a 10-fold dilution series (1:10-1:10(4) ) of DEN-3 virus was
      included. The panel was pre-tested by nested RT-PCR, in-house real-time PCR, and
      a commercial real-time PCR kit. The samples were inactivated by gamma irradiation
      and shipped in freeze dried state. Thirteen laboratories, within the European
      network for the diagnostics of imported viral diseases (ENIVD) took part using
      either single-round, nested, or real-time RT-PCR methods. Two laboratories used
      two methods in parallel, summarising up to 15 comparable results. RESULTS: 33
      100% correct results were achieved. All laboratories detected DEN-2 correctly,
      followed by DEN-1 (14 positive results of 15), DEN-3 (12/15) and DEN-4 (11/15).
      Testing of the serial dilution revealed low sensitivity in many labs, with
      results ranging from 33 to 80% of correctly tested samples. CONCLUSION: The EQA
      gives a feedback of the quality of the RT-PCR system used by each respective
      laboratory. The different test systems and amplification conditions demonstrate
      the importance of external quality control measures.

PMID- 15163415
TI  - Prospects for dendritic cell vaccination in persistent infection with hepatitis C
      virus.
AB  - Although hepatitis C virus (HCV) is classified in the Hepacivirus genus in the
      family Flaviviridae, it is unlike most of the other members of this family due to
      its propensity to cause persistent infections. This persistent infection
      eventually results in chronic liver disease, cirrhosis and hepatocellular
      carcinoma in a proportion of infected individuals. It has been difficult to
      examine correlates of clearance or persistence because most acute phase HCV
      infections are subclinical or result in symptoms which are non-specific;
      consequently, acute infections are not generally recognised and patients often
      present many years later with persistent infection and accompanying chronic liver
      disease. Nevertheless, seminal studies, performed during the acute phase, have
      identified a number of factors which are likely to influence the outcome of
      infection, although it is possible that the mechanism is multifactorial. One of
      these factors is impairment of dendritic cell function by a mechanism resulting
      from expression of an HCV protein(s) in these cells. This may be a major factor
      in the failure of the immune response to expand after HCV infection, leading to
      persistence. Nevertheless, it may be possible to overcome this defect by
      autologous transfusion of HCV antigen-loaded, mature dendritic cells and the
      purpose of this review is to highlight the need and general approaches for
      developing dendritic cell-based immunotherapy for HCV infection.

PMID- 15163417
TI  - One-Step RT-PCR protocols improve the rate of dengue diagnosis compared to Two
      Step RT-PCR approaches.
AB  - Dengue is the most important arboviral disease transmitted to humans. In our
      laboratory, we have been working on the standardization of the polymerase chain
      reaction (PCR) diagnosis of this disease. In this work, we compared five
      commercial kits regularly used on reverse-transcription polymerase chain reaction
      (RT-PCR) protocols: two Two-Step kits (SuperScript II RT/Super Mix kit and
      reverse transcription system/Taq DNA polymerase) and three One-Step kits (ready
      to-go RT-PCR Beads kit, QIAGEN One-Step RT-PCR kit, and AcessQuick RT-PCR
      system). Thirty-one serum samples of patients with clinical diagnosis of dengue
      fever (DF) were analyzed by RT-PCR and serology. RNA extraction was done with the
      QIAamp Viral RNA kit, and cDNA synthesis and PCR done according to the
      manufacturer's protocol for the five kits. Out of the 31 serum samples collected
      from patients suspected of having dengue, 27 were IgM-positive, confirming the
      dengue diagnosis. Out of those, 24 were positive by the ready-to-go RT-PCR Beads
      kit, 25 were positive by AcessQuick RT-PCR system and 27 were positive by QIAGEN
      One-Step RT-PCR kit. On the other hand, only six samples were positive by the
      SuperScript II RT/Super Mix kits and 10 were positive by reverse transcription
      system/Taq DNA polymerase kit. The best performance observed with the One-Step
      kits was confirmed in spiked samples with known quantities of dengue-1 virus
      since they detected up 1 x 10(2) PFU/ml, while the most sensitive Two-Step kit
      detected up 1 x 10(4) PFU/ml. These data show that One-Step RT-PCR kits yielded a
      higher rate of dengue virus detection than the Two-Step kits and correlated well
      with the serological diagnosis.

PMID- 15163418
TI  - PCR detection of human papillomavirus of the mucosa: comparison between MY09/11
      and GP5+/6+ primer sets.
AB  - BACKGROUND AND OBJECTIVES: Human papillomaviruses (HPV) are the causal agent for
      the development of carcinomas in the cervix uteri and further pathological
      changes of the skin including mucosa, particularly warts, condylomas and
      dysplasias. Therefore, we investigated the efficacy of different consensus
      primers pairs for HPV detection by PCR using brushed samples from the oral cavity
      in comparison with samples from the cervix uteri. STUDY DESIGN: In the present
      study, we used two well-established sets of PCR primers in different combinations
      for the detection of HPV DNA in 106 non-invasive brush biopsy samples of the oral
      mucosa and 56 samples from the cervix uteri. Direct sequencing of PCR products in
      all cases determined HPV genotype and specificity. RESULTS: Overall, HPV was
      detected in 69 of 106 oral mucosa samples. HPV specific amplicons were obtained
      in 35.8% (N = 38) when using GP5+/6+ primers. The positivity rate was increased
      to 65.1% in a GP5+/6+ auto-nested PCR approach. In contrast, MY9/11 PCR and
      nested PCR with MY9/11 outer followed by GP5+/6+ inner primers yielded 2.2% and
      16.1%, respectively. In gynaecological samples, PCR results were similar
      independent of the primer combination used. Thus, DNA quality and DNA content
      could be additional factors influencing the rate of positivity. CONCLUSION: For
      oral mucosa samples, auto-nested GP5+/6+ PCR is in our hands the most suitable
      approach for epidemiological studies because of its high sensitivity, high
      reliability and reproducibility as well as its relatively simple laboratory
      procedure.

PMID- 15163419
TI  - Cloning, sequencing, expression, and purification of SARS-associated coronavirus
      nucleocapsid protein for serodiagnosis of SARS.
AB  - A novel coronavirus has been associated with a worldwide outbreak of atypical
      pneumonia referred to as Severe Acute Respiratory Syndrome (SARS-CoV). SARS-CoV
      nucleocapsid (N) protein has been cloned sequenced and expressed in Escherichia
      coli strain. Purified N protein was used to measure the SARS-CoV specific IgG
      antibodies from 16 SARS-CoV infected patients' sera and from 131 control subjects
      using ELISA assay. Specific antibody responses to the purified recombinant N
      protein after 10, 20, and 30 days of disease onset were observed in 13 of 16
      (81.3%), 16 of 16 (100%) and 16 of 16 (100%) SARS patients sera, respectively.
      Comparison of detection results with a commercially available diagnostic kit
      coated with a mixture of SARS-CoV viral proteins showed 9 of 16 (56.3%), 13 of 16
      (81.3%), and 15 of 16 (93.7%) positive responses, respectively. None of 131
      control sera gave positive reaction in either assay. This data suggests that the
      N protein of SARS-CoV is immunodominant and this ELISA based test assay for
      detecting the SARS-CoV N antigen may hold a significant value for SARS diagnosis.

PMID- 15163420
TI  - Inter-laboratory comparison of qualitative and quantitative detection of
      hepatitis C (HCV) virus RNA in diagnostic virology: a multicentre study (MS) in
      Italy.
AB  - BACKGROUND: The importance of the standardisation of nucleic acid amplification
      technology (NAT) assays for the detection of hepatitis C virus RNA is well known
      today, as many studies carried out in different European countries attest. The
      results of a previous study performed in Italy (J. Clin. Virol. 1 (2003) 83) by
      the Italian Society of Clinical Microbiology (AMCLI) showed that the use of
      external reference standards and of multicentre collaborative studies
      significantly improves laboratory performance for the qualitative evaluation of
      HCV RNA. OBJECTIVES: the AMCLI organised a new study on the standardisation of
      both the qualitative and the quantitative evaluation of HCV RNA with NAT in order
      to improve the implementation of the diagnostic methods for HCV RNA detection.
      STUDY DESIGN: seventeen diagnostic centres of major Italian Hospitals
      participated in this quality control study. The study consisted of testing three
      panels, each made up of 10 coded samples including negative and positive samples.
      Positive samples contained four levels of HCV RNA (genotype 1). RESULTS AND
      CONCLUSION: Seven out of 510 qualitative results obtained were incorrect (1.4%),
      two false negative and five false positive. The results gave a sensitivity of
      99.5% and a specificity of 95.8%. Regarding quantitative tests, the geometric
      mean (GM) and standard deviation (S.D.) could be calculated only for the three
      highest HCV RNA levels. The percentage of results within the range of GM +/- 0.5
      log(10) varied from 91% to 100%. Some laboratories had some difficulty in the
      exact quantification of the lowest (3.00 log IU/ml) as well as of the highest
      viral levels (6.35 log IU/ml) values, very near to the limits of the dynamic
      range of the assays. The comparison of the results of this study with that
      previously carried out one confirms that a regular participation in external
      quality assessment (EQA) assures the achievement of a high proficiency level in
      the diagnosis of HCV infection.

PMID- 15163421
TI  - Detection of West Nile virus using formalin fixed paraffin embedded tissues in
      crows and horses: quantification of viral transcripts by real-time RT-PCR.
AB  - West Nile virus (WNV) RNA was quantified in WNV infected crows and horses with
      the help of a real-time reverse transcriptase-PCR assay. A 5' nuclease assay,
      based on NS5 gene detection with a fluorescent probe was used for quantifying WNV
      RNA using formalin fixed paraffin embedded tissue specimens. Quantitative
      detection of WNV RNA showed the presence of a higher amount of the viral RNA in
      crow tissues compared to equine tissues and these results correlated well with
      the detection of WNV antigen by immunostaining. In crows, the highest amount of
      virus was seen in the intestine and in horses in the brain.

PMID- 15163422
TI  - Viral titers in nasal lining fluid compared to viral titers in nasal washes
      during experimental rhinovirus infection.
AB  - BACKGROUND: The concentration of rhinovirus in nasal wash specimens from infected
      volunteers peaks at 48-72 h after inoculation. The volume of expelled nasal fluid
      peaks at the same time, raising the question of whether the viral concentration
      in nasal wash reflects viral replication in nasal cells or merely the production
      of an increased volume of nasal fluid during a cold. OBJECTIVES: To determine the
      amount of rhinovirus in nasal lining fluid during colds before the nasal fluid
      has been diluted in a nasal wash. STUDY DESIGN: Rhinovirus titers were determined
      in nasal wash specimens collected daily for five days from 14 subjects with
      type16 rhinovirus infection. The urea concentration in nasal lining fluid equals
      that in blood. By determining the urea concentration in a nasal wash and
      comparing it to the urea concentration in blood from the same subject, it was
      possible to determine the amount of dilution of the nasal lining fluid. The
      dilution factor (reciprocal of the dilution) was then used to calculate the viral
      concentration in undiluted nasal lining fluid. RESULTS: The dilution factor in 70
      nasal washes varied from 5 to 64. The viral GMTs (+S.E.) in nasal washes were
      1.79 (+0.3) TCID(50)/ml at 24 h, 3.11 (+0.15) at 48 h, and 2.61 (+0.3) at 72 h.
      The viral GMTs in nasal lining fluid, based on urea adjusted values, paralleled
      those in nasal washes but were approximately one log higher. Virus concentrations
      returned to near baseline values by day 5. CONCLUSIONS: The temporal pattern of
      rhinovirus shedding observed in nasal wash specimens, with a peak in virus
      concentration at 48-72 h after infection, is a true indication of virus
      production in nasal cells and not an artifact of the increased amount of nasal
      fluid produced during the early phase of a cold.

PMID- 15163423
TI  - Severe herpes virus (HSV-2) infection in two patients with myelodysplasia and
      undetectable NK cells and plasmacytoid dendritic cells in the blood.
AB  - BACKGROUND: How the immune system contains herpes simplex virus (HSV) infections
      is partly understood. T cells from infected persons proliferate in response to
      HSV antigens in vitro and may control local relapse rather than primary
      infection. NK cells have been involved in the control of experimental infections.
      A potentially important, as yet unexplored, population of interest might be the
      plasmacytoid dendritic cells (PDC), which contrary to monocytes, produce very
      high amounts of the major antiviral molecules, type-I interferon (IFN) following
      interaction with HSV. OBJECTIVES: Measure type-I IFN production, PDC, and NK
      cells in patients with unusually severe HSV infections. STUDY DESIGN: Two female
      patients of 33- and 50-year-old, respectively were referred because of severe
      disseminated HSV2 infection and myelodysplastic marrow. One patient had leukaemia
      and a primary HSV2 infection whereas the other had systemic lupus erythematosus
      (SLE) and a chronic HSV2 infection. The following studies were performed at
      various time points over 18 months: analysis of the lymphocytes and PDC subsets
      phenotype, lymphocyte proliferation assays to recall antigens; generation of NK
      cells in cultures, and production of type-I IFN in serum and by HSV-infected and
      by sendai virus (SV)-infected blood cells. RESULTS AND CONCLUSIONS: PDC and NK
      cells were undetectable in the blood of both patients and NK cells could not be
      generated in culture at the time of ongoing infection. PBMC failed to produce IFN
      after infection with HSV contrasting with a normal T cell proliferation to HSV
      antigens in patient 1. Our observation suggests that innate immunity, through NK
      cells and PDC may control HSV infections, and together with IFN-producing
      capacity, should be investigated in patients with unusually severe HSV
      infections.

PMID- 15163424
TI  - SV40 in human thyroid nodules.
AB  - BACKGROUND: Simian virus 40 (SV40) has been a model experimental system for the
      study of cell transformation and tumorigenesis for many years. The study of SV40
      in humans has aroused interest in the related BK virus (BKV) and JC virus (JCV)
      and their role in human disease. OBJECTIVES: SV40 has been found in a variety of
      human samples, both malignant and normal. Many independent studies have suggested
      that SV40 plays a role for some cancers. However, in most cases the role of SV40
      remains unclear. STUDY DESIGN: The subject of this study consisted of 99 patients
      with thyroid nodules. Both thyroid nodule and normal thyroid tissue were taken
      from each patient to test whether they contained SV40 sequences. RESULTS: We
      detected SV40 sequences by polymerase chain reaction (PCR) in four of 99 thyroid
      nodules. Two of them were papillary thyroid carcinomas and the others were benign
      thyroid nodules. No SV40 was detected in 99 of normal thyroid tissues of the same
      patients. DNA sequence analysis, performed in four positive samples, confirmed
      that PCR products belong to the SV40 T antigen (Tag) region. CONCLUSION: The
      possible role of SV40 in the development of thyroid nodules and the spread of
      SV40 by horizontal infection in the human population are discussed.

PMID- 15163425
TI  - HSV excretion after bone marrow transplantation: a 4-year survey.
AB  - BACKGROUND: Herpes simplex virus (HSV) oral excretions are common after bone
      marrow transplantation (BMT). OBJECTIVE: We report a 4-year systematic survey of
      HSV excretions in an adult population who underwent BMT (289 transplantations).
      STUDY DESIGN: Patients received either intravenous ACV treatment when mucositis
      occurred or systematic intravenous ACV prophylaxis from initiation of the BMT
      conditioning until the end of aplasia. All patients were followed up for HSV
      excretions. RESULTS: Twenty-eight patients (9.7%) excreted HSV. The occurrence of
      HSV excretions was similar in both allogeneic and autologous transplant patients.
      The incidence was significantly lower when ACV was systematically used after
      transplantation (2.5%) compared to when ACV was implemented for mucositis (12%).
      ACV-resistant HSV was detected in three patients who received allogeneic
      transplantation, representing 27% of allogeneic recipients excreting HSV.
      CONCLUSION: HSV infection prophylaxis with high dose of intravenous ACV resulted
      in a decreased incidence of HSV excretion. Nevertheless, the risk of emergence of
      ACV resistance, especially among allogeneic transplant patients, appears to be
      identical whatever the route and dose of ACV prophylaxis.

PMID- 15163427
TI  - The role of hypoxia in the pathogenesis of alcoholic liver disease.
AB  - Research on alcohol-induced liver hypoxia in experimental and clinical alcoholic
      liver disease (ALD) over a span of 20 years is reviewed. The data has repeatedly
      supported a role for hypoxia in the pathogenesis of ALD but little attention has
      been given to this phenomenon in a clinical setting where intervention strategies
      could be developed. Liver hypoxia, particularly when blood alcohol levels are
      high, has been documented in vivo in rats fed ethanol continuously at a constant
      rate for prolonged periods. In this model of ALD, the liver pathology, the liver
      metabolism and the gene expression differ when the livers are compared at the
      peak and trough blood alcohol levels as monitored daily by measuring the urinary
      alcohol level cycle (UAL). Genes regulated by the hypoxia-inducible factor (HIF)
      are expressed more at the peaks, and the livers contain more inflammation at the
      peaks. However, alanine aminotransferase levels are higher at the troughs
      suggesting that hypoxia occurs at the peaks and reperfusion injury occurs at the
      troughs. These findings may be relevant to binge drinking-induced liver injury
      where hypoxia at high BAL is followed by normoxia and reoxygination injury when
      BAL falls toward zero.

PMID- 15163426
TI  - HIV-1 viral load in blood and semen plasma of Brazilian patients under
      antiretroviral therapy.

PMID- 15163428
TI  - Prevalence of Hepatitis C in adults in the south-eastern region of Anatolia: a
      community-based study.
AB  - Aim: There is a limited number of studies on the general population about
      prevalence of Hepatitis C virus (HCV) in Turkey. The estimated prevalence of HCV
      in the Southeastern region of the country was obtained from the data of the blood
      donors. There is no study reflecting the general population of this region,
      leading us to plan this study. Material and method: Four provinces in the
      Southeastern Anatolia were randomly selected and sample sizes were determined by
      Epi Info Programme, and blood samples were collected from 2888 individuals.
      Questionnaires in which demographic information and probable risk factors for
      Hepatitis C were investigated and were applied on subjects who gave their consent
      to participate in the study. Anti-HCV was examined by using Cobas Core II
      immunochemistry system (Roche). All positive samples were further tested for the
      presence of HCV RNA by RT-PCR. Crude odds ratios (OR) and 95% confidence
      intervals (CI) were calculated and Chi-square analyses were performed. Epi Info
      2000 Programme was used to perform the analysis. Results: Of the 2888
      individuals, 17 (0.6%) were anti-HCV positive and 13 (82%) of them were confirmed
      as positive for HCV-RNA. No difference was found between rural and urban regions
      with respect to HCV prevalence ( [Formula: see text] ). The prevalence of HCV in
      35-44 years of age group was found to be different from those of the other age
      groups ( [Formula: see text] ). It was determined that the risk for HCV in this
      age group was 4.23 times ( [Formula: see text]; [Formula: see text];1.02-20.15;
      CI 95%:) higher with a prevalence rate of 1.6%. In this age group, anti-HCV was
      positive in 6 male (2.4%) and 2 female (0.8%), of whom 7 were living in urban
      (2.2%) and 1 in rural area (0.5%). The overall prevalence of HCV was not found to
      be different for sex ( [Formula: see text] ). Similarly, there was no difference
      between the married and single individuals for the prevalence ( [Formula: see
      text] ). Anti-HCV positivity did not change for the level of education. We could
      not determine any factor that might play a role in transmission of HCV.
      Conclusion: This is the first population-based study to be performed in order to
      determine the prevalence of HCV in the south-eastern region of Anatolia (Turkey).
      This region has a low prevalence of HCV. The extremely rare prevalence of
      homosexuality and intravenous drug addiction might have a role in this low
      prevalence.

PMID- 15163429
TI  - Production of IFN-gamma and IL-12 by peripheral whole blood is maintained in
      hepatitis C virus patients with persistently normal alanine transferase activity;
      A preliminary report.
AB  - The current study was designed to investigate the immune status in hepatitis C
      virus (HCV) patients with persistently normal alanine transferase activity (ALT)
      (patients with normal alanine transferase). For this purpose, serum levels and
      lipopolysaccharide (LPS)-induced IFN-gamma, IL12 p70, IL12 p40 and IL-10 as well
      as NK cell activity were assayed in six patients with normal ALT, 22 HCV-infected
      individuals with chronic hepatitis (CH), 13 cases of liver cirrhosis (LC) and 26
      age-matched controls. Cytokine production was assayed with the whole blood
      induction method. IFN-gamma levels were significantly lower in patients with HCV
      infected chronic hepatitis and liver cirrhosis than in controls ( [Formula: see
      text], [Formula: see text] and [Formula: see text] pg/ml, respectively, [Formula:
      see text] ). However, IFN-gamma production in those individuals with normal ALT
      was not reduced ( [Formula: see text] pg/ml). Although variation was observed,
      four of the six patients showed moderate to strong IFN-gamma production. No
      intergroup differences were observed for IL12 p70, IL12 p40 and IL-10 production
      and NK cell activity. Our results suggest that preserved IFN-gamma production in
      patients with normal ALT, in contrast to the reduction in chronic hepatitis and
      liver cirrhosis, may be related to a slow rate of disease progression.

PMID- 15163430
TI  - Changes of HCV quasispecies during combination therapy with interferon and
      ribavirin.
AB  - Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) and
      ribavirin improves the rate of eradication of HCV, but only about 13-14% of non
      responders (NR) with HCV of genotype 1b previously treated with IFN achieve a
      sustained virological response (SVR). To determine whether HCV quasispecies
      diversity correlates with the outcome of therapy with IFN and ribavirin, we
      studied 13 patients undergoing combination therapy with IFN-alpha2b and ribavirin
      after failure of IFN monotherapy. HCV quasispecies diversity was assessed by
      cloning and sequencing before and during combination therapy. During therapy,
      quasispecies diversity diminished in NR patients, both in the hypervariable
      region (HVR) 1 of the envelope 2 (E2) domain and in the interferon sensitivity
      determining region (ISDR) in the NS5A. Pre-treatment nucleotide quasispecies
      diversity was lower in SVR and end-of-therapy viral response (ETR) patients than
      in NR patients. Resistance to ribavirin was associated with high pre-treatment
      heterogeneity and the selection of quasispecies of the HCV genome. HVR
      quasispecies may be a predictor of efficacy of combination therapy with IFN and
      ribavirin.

PMID- 15163431
TI  - Efficacy of non-invasive elastometry on staging of hepatic fibrosis.
AB  - To assess the efficacy of elastmetry in the determination of fibrotic stage in
      the liver, we investigated correlation between liver histology and the
      elastometry using a device equipped with a vibrator and an ultrasound system
      (Echosens, Paris, France) in patients with chronic hepatitis C. Totally 75
      patients, 24 in F1 stage, 17 in F2 stage, 18 in F3 stage, and 16 in F4 stage
      according to the new Inuyama classification without fatty change were
      investigated. Correlations between the staging of liver fibrosis and elastometry,
      serum fibrosis makers and platelet counts were investigated. The elastometry was
      absolutely non-invasive. Serum fibrosis markers did not well correlate with the
      stage of liver fibrosis. Platelet counts significantly ( [Formula: see text] )
      correlated with the fibrotic stage. Median platelet counts in each stage was; F1,
      191.5; F2, 172.0; F3, 132.0; F4, 77.5 (x10(3)microl(-1)). However, the deviation
      was comparatively broad. On the contrary, the elastometry correlated well to the
      stage of fibrosis and the deviation was small. Median elastometric levels in each
      stage were; F1, 6.25; F2, 7.80; F3, 13.85; F4, 34.00 (kPa). These results suggest
      that elastometry is significantly useful for evaluating fibrotic staging of the
      liver without any invasiveness.

PMID- 15163432
TI  - Effect of early octreotide administration on the development of esophageal
      varices in cirrhotic rats.
AB  - This study was conducted to investigate the effect of chronic octreotide
      administration on the development of esophageal varices in rats being at the
      early stages of carbon tetrachloride-induced cirrhosis. For the development of
      liver cirrhosis and esophageal varices 96 rats underwent ligation of left adrenal
      vein followed by phenobarbital and carbon tetrachloride administration. After 2
      weeks of carbon tetrachloride administration, rats were randomly separated into
      three groups. Chronic octreotide administration started in group A, normal saline
      in group B, while 32 rats consisted control group. Haemodynamic studies and
      morphometric analysis of the lower esophagus were performed 2 weeks after
      complete induction of cirrhosis. Total submucosal vessel area, mean cross
      sectional area of submucosal vessels, percentage of submucosa occupied by
      vessels, the area of the most dilated submucosal vessel as well as the number of
      submucosal vessels were studied. Octreotide administration induced a significant
      ( [Formula: see text] ) decrease of portal vein pressure. Morphometric analysis
      revealed a significant reduction ( [Formula: see text] ) in octreotide-treated
      rats of both "total submucosal vessel area" and area of "the most dilated
      submucosal vessel". Chronic octreotide administration partially prevented rats
      from the development of esophageal varices. Octreotide-treated rats were found to
      have a less pronounced dilatation of submucosal veins compared to placebo-treated
      group rats. We believe that this effect was mainly due to the decrease of portal
      vein pressure induced by chronic octreotide administration.

PMID- 15163433
TI  - Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular
      carcinoma.
AB  - Liver cirrhosis accompanies at least 70% of hepatocellular carcinomas world-wide.
      To evaluate the dysregulation of apoptosis and the MAPK pathway in
      hepatocarcinogenesis, we investigated the expression profiles of the genes
      involved in apoptosis and MAPK pathway in cirrhosis and hepatocellular carcinoma.
      A total of 94 tissue specimens (61 cirrhosis and 33 hepatocellular carcinoma)
      obtained from 67 patients were analyzed by microarray, quantitative PCR and
      Western blot experiments. Of 71 apoptosis-associated genes, c-raf-1 and S6 were
      up-regulated in 42.9% and 32.1% of 28 cirrhosis tissues, respectively, and both
      genes were well correlated in a five-cluster K-means analysis. For c-raf-1 and
      down stream genes in the MAPK pathway, c-raf-1, MEK, and MAPK were up-regulated
      in 40%, 80%, and 86.7% of 45 cirrhosis specimens, respectively, and in 50%,
      63.6%, and 59.1% of 22 hepatocellular carcinoma specimens, respectively. Western
      blot analysis showed that activated Raf-1 was over-expressed in 91.2% (52/57) of
      cirrhosis and in 100% (30/30) of hepatocellular carcinoma. The expression level
      of Raf-1 in 14 of 26 paired samples (53.8%) was significantly higher in
      hepatocellular carcinoma than in cirrhosis ( [Formula: see text] -fold, [Formula:
      see text] ). These results suggest that the activation of Raf-1 plays an
      important role in the development of hepatocellular carcinoma.

PMID- 15163434
TI  - Differential diagnosis of hepatic nodules using delayed parenchymal phase imaging
      of levovist contrast ultrasound: comparative study with SPIO-MRI.
AB  - T2-weighted fast spin echo images and T2*-weighted gradient-echo images of
      superparamagnetic iron oxide magnetic resonance imaging (SPIO-MRI) have been
      reported to reflect the number and function of macrophages in reticuloendothelial
      organs and be useful to differentiate malignant tumors from benign nodules of
      liver. We tried to prove that contrast-enhanced ultrasound can diagnose
      hepatocellular carcinoma (HCC) by comparing the findings of SPIO-MRI and the
      findings of the liver parenchyma on the delayed parenchymal phase of ultrasound
      imaging using the intravenous contrast agent Levovist, not through the evaluation
      of vascular imaging. Forty-six patients (52 nodules) with histopathological
      diagnosis of hepatic tumors were studied. They consisted of 11 non-malignant
      nodules (six regenerative nodules and five dysplastic nodules) and 41 HCC. All
      the patients were examined by Levovist contrast-enhanced ultrasonography and SPIO
      MRI. The delayed liver parenchymal images of contrast-enhanced ultrasound using
      the intravenous contrast agent Levovist were similar to those observed on SPIO
      MRI. The similarity of both findings suggests that delayed phase imaging by
      Levovist is closely related to the number and function of Kupffer cells in liver
      tumors. The diagnostic accuracy of contrast-enhanced ultrasound for HCC was high
      (90.4%) demonstrating that it is as reliable as SPIO-MRI.

PMID- 15163436
TI  - Nitric oxide synthase inhibitors augment the effects of serotonin re-uptake
      inhibitors in the forced swimming test.
AB  - The problem of antidepressant-resistant depression has necessitated finding ways
      of augmenting the actions of currently existing antidepressants. The present
      studies investigate the possibility of synergistic interactions between nitric
      oxide (NO) synthase inhibitors and antidepressants in the mouse forced swim test
      (FST), a pre-clinical test of antidepressant activity. Treatment with a
      behaviourally subactive dose of the NO synthase inhibitor NG-nitro-L-arginine (L
      NA) (3 mg/kg) augmented the behavioural effect of the tricyclic antidepressant
      imipramine. In a similar fashion L-NA (3 mg/kg) augmented the effect of the
      selective serotonin re-uptake inhibitor (SSRI) fluoxetine but not the
      noradrenaline re-uptake inhibitor, reboxetine in the FST. The interaction
      observed between L-NA and fluoxetine generalised to other selective serotonin re
      uptake inhibitors, namely, sertraline and citalopram in the FST. Treatment with a
      subactive dose of the neuronally selective NO synthase inhibitor, 7-nitroindazole
      (30 and 50 mg/kg), augmented the behavioural effects of imipramine and
      fluoxetine, respectively. Thus inhibition of NO synthase enhances the activity of
      antidepressants that work via a serotonergic mechanism in the FST. The results of
      the present investigation support a view that antidepressant effects, or
      enhancement of such effects in the FST, may be elicited via NO synthase
      inhibition. Furthermore, these data raise the possibility that inhibition of NO
      synthase could be used as a strategy to enhance the clinical efficacy of
      serotonergic antidepressants.

PMID- 15163437
TI  - Regional mRNA expression of a second tryptophan hydroxylase isoform in postmortem
      tissue samples of two human brains.
AB  - Tryptophan hydroxylase (TPH) as rate limiting enzyme in the biosynthesis of
      serotonin plays a major role as candidate gene in several psychiatric disorders.
      Recently a second TPH isoform (TPH2) was identified in mice, which was
      exclusively expressed in the brain. We investigated whether the mRNA of the human
      homologue of this new TPH2 isoform is expressed in the human brain but not in
      peripheral tissues. The study was performed with postmortem specimen obtained
      from two subjects who died on cardiovascular failure. TPH2 mRNA levels were
      determined by quantitative real time RT-PCR. TPH2 mRNA was exclusively present in
      the human brains but not in the investigated peripheral tissues. Our finding may
      open up new research strategies for the analysis of the repeatedly observed
      disturbances in the serotonergic system in patients suffering from several
      psychiatric disorders.

PMID- 15163435
TI  - Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are
      neurosteroids, produced in the brain, and neuroactive steroids, produced in the
      adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA
      or DHEA-S in schizophrenia patients with normal subjects, and determined the
      correlation of these ratios with psychopathology and distress. Early morning
      plasma concentrations of DHEA, DHEA-S, and cortisol were determined by
      radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects
      with similar age and sex distribution. Subjects were assessed for psychopathology
      using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and
      Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic
      distress levels. Schizophrenia inpatients demonstrated significantly higher
      levels of state and trait anxiety, anger expression index, emotional and somatic
      self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were
      significantly higher in schizophrenia patients than in healthy comparison
      subjects. Both ratios correlated positively with age and duration of illness;
      cortisol/DHEA-S ratio also showed positive association with age of illness onset.
      When age, illness duration and age of onset were controlled, cortisol/DHEA-S
      ratio significantly correlated with severity of depression (MADRS, r=0.33,
      p=0.048), state and trait anxiety (r=0.43, p=0.008 and r=0.40, p=0.014,
      respectively), trait anger (r=0.41, p=0.012), angry temperament (r=0.46,
      p=0.004), anger expression index (r=0.36, p=0.033), and hostility (r=0.42,
      p=0.010). No significant association was found between these ratios and severity
      of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated
      cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are
      positively associated with higher scores for anxiety and anger, depression and
      hostility, age and age of onset/duration of illness, but are independent of
      severity of psychopathology (PANSS) and antipsychotic treatment.

PMID- 15163438
TI  - Effects of acute and repeated administration of a cholinesterase inhibitor on
      timing behaviour.
AB  - It has been hypothesised that a leftward shift in the response distribution
      obtained in the peak interval (PI) procedure is a characteristic of cognitive
      enhancement in which mental processes are speeded. Metrifonate, a cholinesterase
      inhibitor with reported cognitive enhancing properties in many animal models of
      learning and memory, was tested in the PI procedure. Acute administration of 3
      and 60 mg/kg but not 1 and 30 mg/kg in fully trained rats shifted the response
      distribution to the right, whereas subchronic administration of 10, 30 or 50
      mg/kg during task acquisition had no effect on timing behaviour. On the basis of
      the present data, it can be concluded that the effects of a cognition enhancer in
      the PI procedure cannot be predicted from the scalar expectancy theory (SET).
      Furthermore, SET does not appear to be an appropriate tool for analysing the
      acquisition of timing behaviour.

PMID- 15163439
TI  - Impulsivity related to brain serotonin transporter binding capacity in suicide
      attempters.
AB  - Altered monoaminergic activity has earlier been associated with violent suicidal
      behaviour. In this study whole brain binding potential of the serotonin
      transporter (5HTT) and dopamine transporter (DAT) was measured by single photon
      emission computerised tomography (SPECT) in 12 patients after a serious suicide
      attempt and in 12 age, sex and season matched healthy controls. Clinical and
      temperamental assessments were analysed for possible associations with 5HTT and
      DAT. We found no significant 5HTT or DAT differences between patients and
      controls. In patients, but not in controls, there was a significant correlation
      between whole brain 5HTT and DAT. Impulsiveness according to the Marke Nyman
      Temperament (MNT) was significantly correlated to 5HTT in suicide attempters, but
      not in controls. Neither of the transporters could be regarded as a marker for
      serious suicidal behaviour. A previously discussed connection between serotonin
      and dopamine was replicated in this study. In suicide attempters, low 5HTT was
      associated with impulsivity and to some extent with depressive disorder-key
      factors for suicidal behaviour.

PMID- 15163441
TI  - Influence of antazoline and ketotifen on the anticonvulsant activity of
      conventional antiepileptics against maximal electroshock in mice.
AB  - Experimental studies have indicated that the central histaminergic system plays
      an important role in the inhibition of seizures through the stimulation of
      histamine H1 receptors. H1 receptor antagonists, including classical antiallergic
      drugs, occasionally may induce convulsions in healthy children and patients with
      epilepsy. The purpose of this study was to investigate the effects of antazoline
      and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of
      antiepileptic drugs against maximal electroshock (MES)-induced convulsions in
      mice. The following antiepileptic drugs were used: valproate, carbamazepine,
      diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic
      drugs alone or in combination with antazoline or ketotifen were studied on long
      term memory (tested in the passive avoidance task) and motor performance
      (evaluated in the chimney test), acutely and after 7-day treatment with these H1
      receptor antagonists. The influence of antazoline and ketotifen on the free
      plasma and brain levels of the antiepileptics was also evaluated. Antazoline (at
      0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the
      electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses
      of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases,
      antazoline and ketotifen were without effect upon this parameter at lower doses.
      Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine
      against MES (both, acutely and after 7-day treatment). Furthermore antazoline
      (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but
      only after repeated administration, without modifying the brain and free plasma
      level of this drug. Moreover, valproate and phenobarbital did not change their
      protective activity when combined with antazoline. Ketotifen (4 mg/kg) possessed
      a biphasic action, acutely it enhanced the anticonvulsant action of carbamazepine
      and phenobarbital while, following 7-day treatment, reduced the antiseizure
      activity of carbamazepine. Ketotifen did not affect the free plasma or brain
      levels of antiepileptics tested. Only acute antazoline (0.25 mg/kg) applied with
      valproate impaired the performance of mice evaluated in the chimney test.
      Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs
      impaired motor coordination in mice treated with valproate, phenobarbital or
      diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in
      combination with antiepileptic drugs did not disturb long-term memory, tested in
      the passive avoidance task. Similarly, ketotifen (4 mg/kg) did not impair long
      term memory, acutely and after 7-day treatment. However, valproate alone or in
      combination with chronic ketotifen (4 mg/kg) worsened long-term memory. The
      results of this study indicate that H1 receptor antagonists, crossing the blood
      brain barrier, should be used with caution in epileptic patients. This is because
      antazoline reduced the protective potential of diphenylhydantoin and
      carbamazepine. Also, ketotifen reduced the protection offered by carbamazepine
      and elevated the adverse activity of diphenylhydantoin, phenobarbital and
      valproate.

PMID- 15163440
TI  - Zolpidem is not superior to temazepam with respect to rebound insomnia: a
      controlled study.
AB  - This randomised controlled trial was conducted to compare zolpidem to an
      equivalent dose of temazepam with respect to subjective rebound insomnia after
      cessation of 4 weeks of treatment in chronic insomnia (zolpidem 10 mg, n=79;
      temazepam 20 mg, n=84). Both agents improved total sleep time (TST) as well as
      sleep onset latency (SOL) significantly during the 4 treatment weeks. Prevalence
      rates for rebound insomnia, defined as a worsening of TST or SOL of more than 40%
      compared to baseline, were 27% for TST and 53% for SOL in the Zolpidem condition
      and 26% and 58%, respectively, in the temazepam condition. No significant
      differences were found between both agents with respect to rebound insomnia, nor
      with respect to their efficacy or safety. We conclude that in clinical practice
      zolpidem has no advantages over temazepam with respect to rebound insomnia.

PMID- 15163442
TI  - How real are patients in placebo-controlled studies of acute manic episode?
AB  - OBJECTIVE: To determine whether the results from placebo-controlled studies
      conducted in patients with manic episode can be generalised to a routine
      population of hospitalised acute manic patients. METHODS: A list of four most
      prevalent inclusion and the nine most prevalent exclusion criteria was
      constructed for participation in previous randomised-controlled trials (RCTs). On
      the basis of this list, a consecutive series of 68 patients with 74 episodes of
      acute mania who had been referred for routine treatment were retrospectively
      assessed to determine their eligibility for a hypothetical but representative
      randomised controlled trial. RESULTS: Only 16% of the manic episodes would
      qualify for the hypothetical trial (male episodes 28%, female episodes 10%),
      whereas 37%, 20% and 27% of the manic episodes would have to be excluded because
      they did no fulfil one, two or at least three of the inclusion or exclusion
      criteria. The most common exclusion criterion was "no use of contraceptives". If
      this criterion was not taken into account, 28% of the male episodes and 33% of
      the female episodes would qualify for inclusion in the hypothetical study. Apart
      from the use of contraceptives, no significant differences between male and
      female episodes were observed in the reasons for exclusion: 11% suicidal
      ideation, 29% prior mood stabilising medication, 1% depot medication, 22% other
      axis I diagnosis, 27% internal disease somatic disease, 5% neurological disorder,
      15% alcohol use disorder and 10% drug use disorder. CONCLUSION: Only a small
      percentage acute manic episodes in a routine mental hospital seem to qualify for
      a standard placebo-controlled RCT. It could be argued, however, that certain
      exclusion criteria (e.g. no use of contraceptives) are not very likely to reduce
      the external validity of a standard RCT. In contrast, some other exclusion
      criteria (e.g. comorbid alcohol and drug use disorders) may have resulted in an
      overestimation of the efficacy of anti-manic medications. These notions should be
      taken into account when evaluating the results of RCTs in bipolar patients with
      an acute manic episode.

PMID- 15163443
TI  - Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory
      behavior and sensitization to amphetamine.
AB  - Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in
      the CNS may be important in the pathogenesis of psychotic disorders and substance
      abuse. In this study, the effect of coadministration of the selective CCK
      receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and
      CCK2 receptors, respectively), on the effect of amphetamine on the rat
      exploratory behavior, and on sensitization of locomotor response to amphetamine,
      were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the
      exploration box for 5 consecutive testing days, while devazepide (10 microg/kg)
      blocked and L-365,260 (10 microg/kg) enhanced amphetamine-induced stimulation of
      activity. Devazepide coadministration prevented the development of sensitization
      to amphetamine, while coadministration of L-365,260 with amphetamine potentiated
      the locomotor effect of a challenge dose of amphetamine. These results suggest
      that endogenous CCK, released during exploratory activity, shapes behavioral
      responses to amphetamine by acting on both receptor subtypes, and modulates the
      development of sensitization to amphetamine.

PMID- 15163444
TI  - The effect of famotidine addition on olanzapine-induced weight gain in first
      episode schizophrenia patients: a double-blind placebo-controlled pilot study.
AB  - Olanzapine treatment is associated with substantial weight gain. In this double
      blind placebo-controlled study we evaluated whether the H2 antagonist famotidine
      may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM
      IV schizophrenia patients were randomly allocated to receive either famotidine
      (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6
      weeks. All patients completed the trial. Patients in both groups showed a similar
      increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and
      olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of
      0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group
      and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of
      their initial body weight, a cut-off for clinically significant weight gain.
      Famotidine addition was safe and well tolerated and did not interfere with
      olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6
      weeks) is not effective in preventing/attenuating weight gain in olanzapine
      treated first-episode schizophrenia patients.

PMID- 15163445
TI  - Overnight metyrapone and combined dexamethasone/metyrapone tests in post
      traumatic stress disorder: preliminary findings.
AB  - Using overnight metyrapone and combined dexamethasone/metyrapone tests,
      hypothalamic-pituitary-adrenocortical (HPA) axis feedback regulation was
      characterised in 10 patients with post-traumatic stress disorder (PTSD) and 10
      matched healthy comparison subjects. Significant treatment effects of both
      metyrapone and the combination of dexamethasone and metyrapone were observed for
      adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11-DOC) and cortisol, but
      no differences between patients and comparison subjects emerged. Dose-response
      studies using metyrapone and glucocorticoid agonists are needed to further
      investigate HPA axis regulation in PTSD.

PMID- 15163446
TI  - Effects of subchronic clozapine treatment on long-term potentiation in rat
      prefrontal cortex.
AB  - Several studies postulated an interaction of clozapine with N-methyl-D-aspartate
      (NMDA) receptor-mediated transmission. We previously showed that acute clozapine
      application on rat prefrontal cortex (PFC) slices increased NMDA receptor
      dependent long-term potentiation (LTP) in the prelimbic (PL) area. The present
      study explores the effects of subchronic clozapine treatment on LTP in the same
      brain area. After 21 days of treatment (30 mg/kg per day, via drinking water),
      rats were sacrificed and slices from the PFC were prepared for
      electrophysiological investigations. To this end, extracellular field potentials
      in the layer II-V pathway were recorded. In contrast to our previous study with
      acute application on the slice, subchronic clozapine treatment attenuated LTP as
      compared to non-treated animals. We interpret these findings to suggest that
      prolonged treatment with clozapine might result in a compensatory response to the
      acute facilitating action of clozapine on LTP-mediating processes.

PMID- 15163447
TI  - Bright light therapy in seasonal affective disorder--does it suffice?
AB  - Bright light therapy (BLT) has been proposed as treatment of choice for seasonal
      affective disorder (SAD). However, conventional antidepressants have also been
      found to be effective in this condition. We examined the psychopharmacologic
      medication in a clinical sample of 553 SAD patients, who had been treated with
      BLT, to assess the importance of drug treatment and to critically question the
      effectiveness of BLT. Forty-nine percent of our patients received
      psychopharmacologic treatment and about one third (35.4%) was treated with
      antidepressants, suggesting that BLT does not suffice as only antidepressant
      regimen for all SAD patients. Furthermore, our results show that only few
      patients with bipolar affective disorder were willing to accept long-term
      medication. Opposed to treatment guidelines, patients with several depressive
      episodes did not receive antidepressant maintenance medication or mood
      stabilizers more often than patients with only a few episodes.

PMID- 15163448
TI  - Detecting malingering: a survey of experts' practices.
AB  - A survey addressing practices of 'expert' neuropsychologists in handling
      financial compensation claim or personal injury litigation cases was carried out.
      Potential participants were identified by publication history. Responses were
      obtained from 24 out of the 39 neuropsychologists who were surveyed.
      Approximately 79% of the respondents reported using at least one specialized
      technique for detecting malingering in every litigant assessment. Half stated
      that they always give specialized tests at the beginning of the assessment. The
      Rey 15-Item test and the Test of Memory Malingering were the most frequently
      reported measures. Respondents also reported frequent use of 'malingering'
      indexes from standard neuropsychological tests. Reported base-rates varied, but
      the majority of respondents indicated that at least 10% of the litigants they
      assessed in the last year were definitely malingering. Respondents were split on
      the practice of routinely giving warnings at the outset of assessments that
      suboptimal performance may be detected. However, when the client's motivational
      status was suspect, more than half (58.3%) altered their assessment routine at
      least on some occasions, by encouraging good effort (70.8%) or administering
      additional SVTs. A minority directly confronted or warned clients (25%),
      terminated the examination earlier than planned (16.6%), or contacted the
      referring attorney immediately (29.2%). Respondents almost always stated some
      opinion regarding indicators of invalidity in written reports (95%). However,
      41.7% rarely used the term 'malingering' and 12.5% never used the term. Most
      respondents (>80%) instead stated that the test results are invalid, inconsistent
      with the severity of the injury or indicative of exaggeration.

PMID- 15163449
TI  - A comparison of WMT, CARB, and TOMM failure rates in non-head injury disability
      claimants.
AB  - Two-alternative forced-choice procedures have been the most widely employed for
      detecting incomplete effort and exaggeration of cognitive impairment. However, it
      cannot be assumed that different symptom validity tests (SVTs) are of equal
      sensitivity. In this study, 519 claimants referred for disability or personal
      injury related assessments were administered three SVTs, one based on digit
      recognition (Computerized Assessment of Response Bias, CARB), one using pictorial
      stimuli (Test of Memory Malingering, TOMM) and one employing verbal recognition
      memory (Word Memory Test, WMT). More than twice as many people failed the WMT
      than TOMM. CARB failure rates were intermediate between those on the other two
      tests. Thus, tests of recognition memory using digits, pictorial stimuli or
      verbal stimuli, all of which are objectively extremely easy tasks, resulted in
      widely different failure rates. This suggests that, while these tests may be
      highly specific, they vary substantially in their sensitivity to response bias.

PMID- 15163450
TI  - Performance profiles and cut-off scores on the Memory Assessment Scales.
AB  - The increased role of neuropsychologists in the courtroom has led to an increased
      effort in the detection of possible symptom exaggeration/malingering. Whereas
      domain specific measures of malingering have traditionally been used in this
      detection process, the identification of performance profiles and cut-off scores
      on standard neuropsychological assessment instruments may provide an alternate
      strategy. The present study evaluated the effectiveness of performance profiles
      and cut-off scores in discriminating traumatic brain injury (TBI) litigants
      suspected of malingering from those not suspected of malingering on the Memory
      Assessment Scales (MAS). Results suggest that TBI litigants suspected of poor
      effort will perform globally at a lower level than TBI litigants not suspected of
      poor effort on nearly all MAS indices, however, the performance profiles of each
      group was similar. Cut-off scores, especially when used in combination, were also
      effective in correctly classifying individuals in the two groups. The present
      findings warrant further research examining the utility of the proposed cut-off
      scores separately and concomitantly. Such research will aid the clinical
      neuropsychological practitioner in interpreting aberrant performance profiles on
      the MAS in forensic situations.

PMID- 15163451
TI  - The effect of acute stress on subsequent neuropsychological test performance
      (2003).
AB  - Acute mental stressors have been implicated as variables that may deleteriously
      affect neuropsychological test performance by increasing distractibility and
      decreasing working memory function. This study examined 25 subjects with no known
      neurological or psychiatric impairment on a brief battery of neuropsychological
      measures on alternate days following either rest or induced mental stress in a
      counterbalanced design. The test battery consisted of the Rey Auditory-Verbal
      Learning Test, the Rey Complex Figure, and three Wechsler Memory Scale-III
      subtests (Logical Memory, Digit Span, and Visual Memory Span). The Ss average age
      was 24.8 years (S.D. = 10.1) and average education was 15.0 years (S.D. = 1.6).
      The mental stressor employed was a videotaped public-speaking exercise that has
      been shown in previous work to induce negative mood, cardiovascular reactivity,
      and perceived mental stress. Ss demonstrated statistically significant (P < .05)
      increases in negative mood, heart rate, diastolic blood pressure, and systolic
      blood pressure as well as elevated cortisol concentration following induced
      stress, suggesting substantially increased adrenocortical reactivity and
      cardiovascular stress response. There were, however, no statistically significant
      differences in any of the neuropsychological measures when stress versus rest
      days were compared. The results suggest that acute mental stressors may have no
      measurable effect on subsequent performance on selected neuropsychological tests
      in a normal population. Further work is suggested to determine whether pre
      existing anxiety-related psychopathology or pre-existing neurological compromise
      might interact with induced mental stress to cause decrements in
      neuropsychological test performance.

PMID- 15163452
TI  - Speed of presentation influences story recall in college students and persons
      with multiple sclerosis.
AB  - Story memory tests are commonly used in clinical neuropsychology. Surprisingly,
      no guidelines are provided for speed of presentation for two of the most commonly
      used story memory tests in clinical neuropsychology. The current investigation
      was designed to explore whether speed of presentation influences recall on the
      Story subtest from the Rivermead Behavioural Memory Test. Consistent with
      predictions, college students in Study 1 and multiple sclerosis participants in
      Study 2 recalled significantly more story elements at immediate recall when the
      story was presented slow versus fast. This effect, however, was limited to the
      conditions where the fast story was presented before the slow story. At delayed
      recall, participants in both studies recalled more story elements in the slow
      versus fast story independent of presentation conditions. Both studies also
      revealed that significantly more participants fell in the "impaired" range on
      immediate recall for the fast story in the condition where it was presented
      first. Data from these studies show that speed of presentation can substantially
      alter story recall in a wide range of individuals. It will be important to
      develop story tests for which speed of presentation is standardized to ensure
      that erroneous conclusions regarding memory are not drawn about individuals seen
      in clinical neuropsychological practice.

PMID- 15163453
TI  - Symptom validity testing of feigned amnesia for a mock crime.
AB  - Perpetrators sometimes claim loss of memory for the crimes they have committed.
      For the neuropsychologist, the veracity of such crime-related amnesia is
      difficult to assess. The aim of the present study was to investigate whether
      Symptom Validity Testing (SVT) can be used to detect feigning of crime-related
      amnesia. Undergraduate students (N = 39) were instructed to commit a mock crime
      and asked to feign complete amnesia for the event. Subsequently, they were given
      25 forced-choice items about the "crime" that were always followed by the correct
      answer and an equally plausible alternative. To counteract chance performance,
      test items were intermixed with 25 bogus questions that contained two equally
      plausible alternatives. Results show that a majority of participants (59%) scored
      below chance level on the critical items of the SVT. In addition, debriefing
      interviews showed that understanding the rationale behind the SVT was not related
      to chance performance. SVT procedures therefore might be helpful in identifying
      feigned crime-related amnesia.

PMID- 15163454
TI  - Setting empirical cut-offs on psychometric indicators of negative response bias:
      a methodological commentary with recommendations.
AB  - Malingering in neuropsychological assessment has been the subject of intense
      research for more than a decade and the detection methods arising from this work
      are diverse and sophisticated. However, the empirical findings are often
      presented in ways that limit the clinical utility of these techniques and may
      threaten their admissibility into legal proceedings. The purpose of this paper is
      to outline an approach for setting cut-offs on techniques designed to identify
      the presence of negative response bias. The use of this approach will result in
      the explicit specification of the error rate(s) of a given technique which can
      easily be applied by clinicians in the course of their practice and be admissible
      in court.

PMID- 15163455
TI  - The physiological experience of the Paced Auditory Serial Addition Task (PASAT):
      does the PASAT induce autonomic arousal?
AB  - Previous research suggests that the Paced Auditory Serial Attention Task (PASAT)
      alters mood states, which may induce performance changes and complicate
      interpretation test scores. In the current design, we examined arousal as one
      mechanism moderating PASAT performance. It was expected that arousal level would
      increase during the test, and performance on the test would be related to arousal
      level. Heart rate and blood pressure (systolic and diastolic) were recorded from
      42 healthy adult men during rest and PASAT challenge. Heart rate and blood
      pressure were significantly higher and stable across the PASAT procedure, while
      performance scores showed a steady decrease in correct responses. No association
      of arousal level and performance was found. Although, PASAT induced arousal
      changes were not significantly related to performance among healthy adults, the
      observed arousal changes do raise concerns about interpretation of PASAT
      performance among more sensitive populations and indicate new areas of
      application of the procedure.

PMID- 15163456
TI  - A new interference score for the Stroop test.
AB  - A New interference calculation method for the Stroop test was developed based
      upon a neuropsychological model of the suppression of word reading in favor of
      color naming. Polynomial regression equations show a significant relationship
      between word reading and the New interference score that closely fits the
      underlying prediction of the New model, while the Golden [Stroop Color and Word
      Test, Stoelting Co., IL, Wood Dale, 1978] model (Old) produces only a random
      relationship. Constructs of developmental maturation and lateralized brain damage
      are supported by the New but not the Old method. The New compared to the Old
      method also gives a significant reduction in scores in a small sample of demented
      patients. It would be advisable to use this New model in both cognitive and
      neuropsychological comparisons of different lesions or different stimulus and
      response demands. The New model will also help promote finer clinical inferences
      when an understanding relative to the patient's own baselines is necessary.

PMID- 15163457
TI  - Executive functioning in boys with ADHD: primarily an inhibition deficit?
AB  - This study was aimed at: (1) testing whether boys with Attention
      Deficit/Hyperactivity Disorder (ADHD) demonstrate a deficit in response
      inhibition and deficits in other executive functions (EF), or alternatively,
      demonstrate a deficit in only response inhibition; (2) investigating which role
      associated factors, such as IQ, age, and performance on non-EF tasks play in EF
      in ADHD; (3) studying the association between the three different forms of
      inhibition studied here. Boys with ADHD were compared with normal control (NC)
      boys on five domains of executive functioning: inhibition (inhibition of a
      prepotent response, inhibition of an ongoing response, and interference control),
      planning, set-shifting, working memory, and verbal fluency. Boys with ADHD
      demonstrated deficits in interference control, inhibition of an ongoing response,
      planning, and letter fluency. After controlling for age, IQ, and non-EF measures,
      none of the EF deficits in ADHD remained. Finally, correlations between different
      inhibition measures were generally low, and correlations within domains of
      inhibition were not higher than correlations between domains of inhibition. This
      calls into question the distinctiveness of the different forms of response
      inhibition.

PMID- 15163458
TI  - Transition metal-induced apoptosis in lymphocytes via hydroxyl radical
      generation, mitochondria dysfunction, and caspase-3 activation: an in vitro model
      for neurodegeneration.
AB  - BACKGROUND: Redox transition metals have been implicated as crucial players in
      pathogenesis of neurodegenerative diseases. Intracellular signaling mechanism(s)
      responsible for oxidative stress and death in single-cell model exposed to metals
      has not yet been fully elucidated. The objective of the study was to determine
      the mechanism by which metals induced apoptosis in human peripheral blood
      lymphocytes (PBL). METHODS: PBL were exposed to 50, 100, 250, 500, and 1,000
      microM (Fe2+), (Mn2+), (Cu2+), and (Zn2+)-(SO4). Apoptotic/necrotic morphology
      was assessed with acridine orange/ethidium bromide staining. Further evaluations
      comprised production of H2O2, generation of hydroxyl radical (.OH), disruption of
      mitochondrial transmembrane potential (DeltaPsim), caspase-3 activation, and
      activation of NF-kappaB and p53 transcriptional factors. RESULTS: Morphologic
      analysis showed that 500 microM provoked maximal percentage of apoptosis (22-30%
      AO/EB) and minimal necrosis (3-7%), whereas low concentrations were innocuous but
      1,000 microM induced mainly necrosis (>40% AO/EB). Metals generated both H2O2 and
      (.OH) by Fenton reaction. Hydroxyl scavengers protected PBL from metal-induced
      apoptosis. All metals induced mitochondrial depolarization (17-62% nonfluorescent
      cells) and activated caspase-3 concomitantly with apoptotic morphology (25-32%
      AO/EB) at 24 h, and neither NF-kappaB nor p53 transcription factor showed
      activation. CONCLUSIONS: This study provides evidence that redox-active (Fe2+),
      (Mn2+), (Cu2+), and (Zn2+) ion-induced apoptosis in PBL by (H2O2)/(.OH)
      generation, resulting in mitochondria depolarization, caspase-3 activation, and
      nuclear fragmentation independent of NF-kappaB and p53 transcription factors
      activation. Our data highlight the potential use of lymphocytes as a model to
      screen antioxidant strategies designed to remove H2O2/.OH associated with metal
      catalyzed reactions in neurodegenerative disorders.

PMID- 15163459
TI  - A single amino acid change within the ion-channel domain of the gamma
      aminobutyric acid rho1 receptor accelerates desensitization and increases taurine
      agonism.
AB  - BACKGROUND: GABAC receptors are part of the ligand-gated ion channel family of
      receptors that share some functional and structural features: e.g., they have
      four putative transmembrane domains (TM1-TM4) and the TM2-segment is presumed to
      form the ion-channel. GABAC receptors open chloride channels and do not
      desensitize even after long exposures to GABA. These receptors are highly
      expressed in vertebrate retina, where they may play a unique role due to their
      unusual biophysical and pharmacologic characteristics. METHODS: To determine
      whether the TM2 domain plays a role in the process of desensitization of GABAC
      receptors, we used site-directed mutagenesis to produce several permutations
      within the leucine (L9') residue of the TM2 domain of the human GABArho1 subunit.
      Recombinant receptors were expressed in Xenopus laevis oocytes and their
      functional and pharmacologic properties were studied by using a two
      microelectrode, voltage-clamp. RESULTS: Several amino acid changes led to
      receptors that did not generate GABA-currents, whereas an Asp for Leu mutation in
      the well-conserved L9' position of the rho1 subunit (L301D-rho1) generated a fast
      desensitizing, bicuculline-resistant receptor that was antagonized by TPMPA, a
      specific GABAC receptor antagonist. Moreover, in contrast with wild-type rho1
      receptors, which are practically not gated by taurine, L301D-rho1 mutant
      receptors generated substantial taurine-currents. CONCLUSIONS: Substitution of
      L9' residue in the TM2 region of GABArho1 receptor for an amino acid residue with
      an acidic lateral chain greatly accelerates its desensitization rate and
      increases taurine-agonism. This mutant will be useful to study mechanisms
      involved in gating and desensitization of GABAC receptors in particular, and of
      neurotransmitter receptors in general.

PMID- 15163460
TI  - A 63 kDa VSP9B10A-like protein expressed in a C-8 Giardia duodenalis Mexican
      clone.
AB  - BACKGROUND: It is well documented that Giardia duodenalis undergoes surface
      antigenic variation both in vivo and in vitro. Proteins involved have been
      characterized and referred to as VSP (variable surface protein). METHODS: Two
      cloned cDNA inserts of 0.45 and 1.95 kb were obtained from G. duodenalis
      expression library and sequenced. Comparison sequence analyses were made against
      Genbank. PCR analysis was performed on G. duodenalis isolates to identify
      isolates bearing genes encoding such a peptide. Specific antiserum was prepared
      against 450-bp encoded peptide and tested by Western blot, immunofluorescence,
      and inhibition of adhesion of G. duodenalis to target cells. RESULTS: We cloned
      and characterized a G. duodenalis 450-bp DNA fragment; its DNA sequence analysis
      revealed that this fragment displayed 99% identity with vsp9B10A gene. Predicted
      amino acid sequence for this fragment also had significant (99%) identity to
      VSP9B10A. A second 1.95-kb insert, which encompassed the 450-bp cDNA fragment,
      was also isolated; its DNA and amino acid sequence displayed 99.5% identity with
      vsp9B10A gene and 99.2% with the corresponding inferred protein, respectively.
      This inferred protein contained 24 Cys-X-X-Cys motifs and long ORF of 642
      aminoacids. PCR analysis showed that DNA sequence encoding a fragment of this
      gene was present in P1, CIEA:0487:2-C-8 clone and in INP:180800-B2 G. duodenalis
      human isolates, while it was absent in sheep isolate of G. duodenalis INP:150593
      J10. CONCLUSIONS: Immunofluorescence analysis using antibodies raised against the
      peptide encoded by 450-bp fragment showed that expression of this epitope varies
      on trophozoite surface of the C-8 Mexican clone and is involved in parasite
      adhesion to target epithelial cells.

PMID- 15163461
TI  - Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with
      cytogenetic tests in vivo.
AB  - BACKGROUND: Growth-modulating noncytotoxic activity of 8-chloro-adenosine 3',5'
      cyclic monophosphate (8-Cl-cAMP) showed inhibitory effect on growth of a wide
      variety of cancer cell lines in vitro and in vivo. To assess possible genotoxic
      effects of 8-Cl-cAMP, we conducted a study in vivo using male BALB/c mice.
      METHODS: Clastogenic effects were estimated by bone marrow micronucleus assay and
      cytogenetic test in adult mice BALB/c strain. 8-Cl-cAMP was administered
      intraperitoneally (i.p.) to three dose groups including 10 mg/kg body weight
      (b.w.), 90 mg/kg b.w., and 160 mg/kg b.w., with saline solution as negative
      control and cyclophosphamide, a known mutagen, and clastogen as positive control
      during a 7-day period in 24-h intervals. RESULTS: Micronucleus test in vivo
      results showed consistently increasing dose-dependent pattern increase of dose
      regime (10 mg/kg body weight [b.w.], 90 mg/kg b.w., and 160 mg/kg b.w.), and
      increase in frequency of micronuclei in polychromatic erythrocytes (4.88 +/-
      0.35, 8.32 +/- 0.57, and 11.74 +/- 0.37) compared to negative control (2.04 +/-
      0.28). Quantitative effects are paralleled by structural changes in chromosome
      morphology. 8-Cl-cAMP induced structural (breaks, gaps, centric rings, acentrics,
      and Robertsonian translocations) and numerical-type chromosomal aberrations
      (aneuploidy and polyploidy). CONCLUSIONS: Results of this study demonstrate that
      8-Cl-cAMP has genotoxic potential in vivo.

PMID- 15163462
TI  - Insulin increase in colon cancerogenesis: a case-control study.
AB  - BACKGROUND: Our aim was to establish whether individuals who develop colon cancer
      have elevated blood insulin concentrations. METHODS: This was a case-control
      study in which 56 normoglycemic patients with colon cancer and a corresponding
      control group were investigated at the Clinical Hospital Split from April 1998 to
      April 1999. Data on age, weight, height, and sex of examinees were recorded and
      concentrations of glucose, insulin, and C-peptide were measured first in the
      morning before breakfast and again 90 min after breakfast. RESULTS: In the male
      group of colon cancer patients, we found statistically significant higher blood
      insulin concentrations 90 min after breakfast (median 34.7 mIU/L, range 3.3-162.6
      mIU/L) in comparison to male control group (median 20.7 mIU/L, range 3.1-122.1
      mIU/L) (p=0.044). Concentration of C-peptide in blood 90 min after breakfast
      (median 3.28 nmol/L, range 0.38-6.1 nmol/L) was higher in the male group of colon
      cancer patients than in male control group (median 1.68 nmol/L, range 0.26-4.26
      nmol/L) (p=0.001). No difference was found in concentrations of insulin, C
      peptide, and glucose in blood measured in the morning before breakfast between
      the male group of colon cancer patients and male control group. Ratio of insulin
      90 min after breakfast with respect to insulin in the morning before breakfast
      was higher in the male group of colon cancer patients (median 4.65, range 0.83
      22.1) than in male control group (median 1.78, range 0.38-8.75) (p=0.005). Ratio
      of C-peptide 90 min after breakfast with respect to fasting C-peptide was higher
      in the male group of colon cancer patients (median 3.22, range 0.74-11.9) than in
      male control group (median 1.42, range 0.54-6.0) (p=0.001). Women with colon
      cancer also had statistically significant higher ratio of insulin and C-peptide
      with respect to female control group. In the female group of colon cancer
      patients, median for ratio of C-peptide was 2.42 (range 0.43-8.87), while in
      female control group it was 1.19 (range 0.62-15.4) (p=0.025). Median for ratio of
      insulin in the female group of colon cancer patients was 4.23 (range 0.25-8.54),
      while in female control group it was 1.17 (range 0.29-26.89) (p=0.007).
      CONCLUSIONS: There was a higher increase of insulin 90 min after breakfast in the
      group of patients with colon cancer than in control group.

PMID- 15163463
TI  - Inflammation in patients on peritoneal dialysis is associated with increased
      extracellular fluid volume.
AB  - BACKGROUND: Cardiovascular disorders (CD) are the most frequent cause of death in
      patients on dialysis. CD have been related to increased extracellular fluid
      volume, peritoneal transport type (PTT), hypertension, and inflammation.
      Inflammation is in itself a risk factor for mortality. The aim of this study was
      to assess the relationship of increased extracellular fluid volume, inflammation,
      and PTT in patients on continuous ambulatory peritoneal dialysis (CAPD) and
      automated peritoneal dialysis (APD). METHODS: A cross-sectional study was carried
      out with 20 healthy controls (C), 21 patients on CAPD, and nine patients on APD.
      Clinical and demographic variables were measured and registered. Peritoneal
      equilibrium test (PET) was done. Blood volume (BV), total body water (TBW),
      inferior vena cava diameter during inspiration (IVCDi) and expiration (IVCDe),
      serum albumin, and serum C-reactive protein (CRP) were measured. RESULTS: All
      patients on peritoneal dialysis (PD) had at least one sign or symptom of
      increased extracellular fluid volume, hypertension being the most common.
      Patients also had higher TBW (C, 60.7 +/- 7.2; APD, 62.6 +/- 8.7; CAPD, 66.1 +/-
      8.3, as percentage of body weight, p <0.02), higher BV (C, 7.9 +/- 1.6; APD, 9.8
      +/- 2.3; CAPD, 9.6 +/- 2.3, as percentage of body weight, p <0.02), higher DIVCi
      (C, 2.9 +/- 1.2; APD, 4.6 +/- 2.5; CAPD, 4.5 +/- 2.4 mm/m2 BSA, p <0.02), and
      higher DIVCe (C, 6.2 +/- 1.7; APD, 8.3 +/- 3.4; CAPD, 8.0 +/- 2.8 mm/m2 BSA, p
      <0.05). PD patients also had hypoalbuminemia and higher CRP levels. There was
      significant positive correlation between CRP and DIVCi (r=0.43, p <0.05) and IVCe
      (r=0.45, p <0.05) and between serum albumin and creatinine dialysate-to-plasma
      ratio (D/P Cr, r=0.57, p <0.01). Serum albumin and CRP were negatively correlated
      (r= -0.54, p <0.02). CONCLUSIONS: Patients on PD have increased extracellular
      fluid volume as compared with healthy controls. Hyperhydration is related to
      inflammation and to higher peritoneal transport types.

PMID- 15163464
TI  - Variable resolution electromagnetic tomography (VARETA) in evaluation of
      compression of cerebral arteries due to deep midline brain lesions.
AB  - BACKGROUND: Hemispheric tumors produced electroencephalographic (EEG) delta
      activity mainly due to deafferentation of cerebral cortex. In small, deep midline
      lesions that compressed cerebral arteries, the most important abnormality should
      have been in EEG theta band that selectively responded to brain ischemia.
      Frequency domain-variable resolution electromagnetic tomography (FD-VARETA) has
      been applied satisfactorily to the study of brain tumors, cerebral infarcts, and
      brain hemorrhages and was shown to localize areas of hypoperfusion. METHODS:
      Twelve patients with deep midline lesions compressing different cerebral arteries
      were studied. Computer tomography (CT) and/or magnetic resonance imaging (MRI) as
      well as quantitative EEG with source calculation in frequency domain were
      obtained. Brain electromagnetic tomographies (BETs) were calculated to evaluate
      localization and extension of functional abnormalities. RESULTS: Ten of twelve
      cases presented abnormal sources in theta band as main abnormal source. In only
      two cases was the main source in delta band, but these cases also had abnormal Z
      values in theta band. In four patients there were only abnormal values in theta
      range. Sources of abnormal theta activity were observed in regions irrigated by
      the arteries compressed. CONCLUSIONS: In deep midline lesions, compression of
      cerebral arteries producing relative ischemia may explain abnormal EEG sources in
      theta band. Patients with main source in theta band showed vascular compression
      and some patients exhibited vasogenic edema. Thus, theta might be due to relative
      ischemia produced by both hypoperfusion and edema. Once again, VARETA has found
      to be very useful in evaluation of functional abnormalities.

PMID- 15163465
TI  - A mutation in the 5,10-methylenetetrahydrofolate reductase gene is not associated
      with preeclampsia in women of southeast Mexico.
AB  - BACKGROUND: We investigated the possible association between C677T-5,10
      methylenetetrahydrofolate (MTHFR) polymorphism and preeclampsia in women from the
      Yucatan Peninsula in Mexico. METHODS: We performed a comparative study among
      three groups of subjects: 148 preeclamptic women; 177 women with normal
      pregnancies, and 313 healthy volunteers as control group. All subjects were
      genotyped for C677T polymorphism in MTHFR gene by PCR amplification and digestion
      of the product with Hinf I restriction enzyme. Genotypic and allelic frequencies
      were compared between affected women (preeclamptic) and nonaffected groups to
      determine the association using Fisher exact test. Odds ratios (ORs) were also
      calculated to obtain estimation of relative risk (RR) for developing
      preeclampsia. RESULTS: Statistical analysis of intergroup comparisons among
      preeclamptic women, women with normal pregnancies, and control group showed no
      statistically significant differences for any genotype or for T allele (p >0.05).
      CONCLUSIONS: Our results suggest that C677T-MTHFR polymorphism is not an
      associated risk factor for developing preeclampsia in southeast Mexico. Results
      also confirmed high prevalence of C677T mutation in Mexico.

PMID- 15163466
TI  - Paraoxonase 1 and platelet-activating factor acetylhydrolase activities in
      patients with low hdl-cholesterol levels with or without primary
      hypertriglyceridemia.
AB  - BACKGROUND: Previous studies have shown that high density lipoprotein (HDL)
      deficient states are associated with reduced paraoxonase 1 (PON1) activity.
      However, HDL reduction caused by primary hypertriglyceridemia has not been fully
      explored. The aim of the present study was to evaluate whether PON1 and platelet
      activating factor acetylhydrolase (PAF-AH), two antioxidant enzymes, were altered
      in patients with low HDL-cholesterol levels with or without primary
      hypertriglyceridemia in comparison with control normolipemic subjects. METHODS:
      We studied 24 patients with low HDL-cholesterol levels with (n=12) or without
      (n=12) primary hypertriglyceridemia in comparison with 12 control subjects who
      presented normal HDL-cholesterol and triglyceride levels. Paraoxon and
      phenylacetate were used as substrate for measuring PON1 activities and 1
      hexadecyl-2-[3H]acetyl-glycero-3-phosphocholine for platelet-activating factor
      acetylhydrolase (PAF-AH) activity. Double substrate method was used to assign
      phenotypes. Lipid, lipoprotein, apolipoprotein, and lipoprotein particles were
      determined by standardized methods. RESULTS: Both PON1 activities were
      significantly reduced in patients with low HDL-cholesterol levels. This reduction
      could be selectively attributed to the hypertriglyceridemic subgroup. PAF-AH
      activity was not different between hypoalphalipoproteinemic patients and
      controls. PON1 activities correlated positively and significantly with HDL
      cholesterol, HDL2-cholesterol, HDL3-cholesterol, HDL-phospholipids, apo A-I, apo
      A-II, and LpA-I:A-II. PAF-AH correlated positively and significantly with total
      and low density lipoprotein-cholesterol. CONCLUSIONS: Data from this study would
      suggest that in hypoalphalipoproteinemic syndrome, particularly when associated
      with hypertriglyceridemia, there is impairment in enzymatic antioxidant activity
      exclusively related with HDL.

PMID- 15163467
TI  - Lower agreement on behavioral factors than on medical conditions in self-reported
      data among pregnant Latina women.
AB  - BACKGROUND: Agreement between self-reported data and data obtained from medical
      records is far from perfect and few studies have analyzed the element of language
      when self-reported data are given in one language and this information is
      recorded in another language in the medical record. Our objective was to assess
      agreement between self-reported data and medical record data with regard to
      prenatal risk factors in pregnant Latina women. METHODS: We interviewed 350
      Latina women at >or =20 weeks' gestation regarding alcohol use, tobacco use, use
      of prenatal vitamins, age, education, use of prenatal care, and medical
      conditions. Kappa statistic (kappa) and 95% confidence intervals (95% CIs) were
      used to calculate agreement between self-reported responses and medical record
      data. Multiple logistic regression analysis was used to evaluate effect of
      maternal characteristics on likelihood of disagreement. RESULTS: Agreement
      between self-reported and medical record data was generally lower for behavioral
      factors (alcohol kappa=0.37 and prenatal vitamin use kappa=0.09) than for medical
      conditions (anemia kappa=0.63, gestational diabetes kappa=0.83, and hypertension
      kappa=0.68). In general, maternal characteristics did not significantly predict
      patterns of disagreement. CONCLUSIONS: Among pregnant Latina women, self-reported
      data on behavioral factors had lower agreement than self-reported data on medical
      conditions. Further study is needed to define the effect of other factors, such
      as social norms, on accuracy of self-reported data during pregnancy.

PMID- 15163468
TI  - Smoking-induced leukocytosis can persist after cessation of smoking.
AB  - BACKGROUND: Associations between smoking and leukocytosis or elevated hemoglobin
      concentrations in the blood need to be validated using multivariate analysis.
      METHODS: A total of 2,511 male subjects aged 25-62 years participated in an
      annual health examination held at their workplace. The relationship between white
      blood cells (WBC) and hemoglobin (Hb) levels in blood and smoking status was then
      evaluated using a cross-sectional survey and multiple logistic regression
      analysis. Age, body mass index (BMI), smoking and drinking status, diastolic
      blood pressure, and physical activity were used as covariate factors. RESULTS:
      Odds ratios (ORs) and 95% confidence intervals (95% CIs) of WBC of >9,000
      counts/mm3 of total blood for current smokers and ex-smokers with a period of 5
      9.9 years since smoking cessation vs. that of nonsmokers were 12.1 (7.0-21.0) and
      3.8 (1.2-12.0), respectively. OR (95% CI) of Hb level >16 g/dL of total blood for
      current smokers vs. nonsmokers was 1.6 (1.1-2.3). Significant ORs for elevated Hb
      level in total blood were also observed for age (OR, 1.0; 95% CI, 0.9-1.0), BMI
      >25 (OR, 2.2; 95% CI, 1.6-3.1), and diastolic blood pressure of >90 mmHg (OR,
      2.2; 95% CI, 1.5-3.2). CONCLUSIONS: Current smoking is associated with increase
      in WBC count and Hb levels in total blood, the former relationship recognized in
      subjects who have stopped smoking for 5-9.9 years. Obesity and aging are
      inversely related with Hb level in blood.

PMID- 15163469
TI  - Relationship between clinical and environmental isolates of Pseudomonas
      aeruginosa in a hospital setting.
AB  - BACKGROUND: Populations of Pseudomonas aeruginosa have been extensively studied,
      although there is no general agreement concerning their genetic structure. It has
      been proposed that P. aeruginosa is a very homogeneous species with 90% of
      individuals within the same clonal group; nonetheless, other results suggested
      that Pseudomonas populations are panmictic. Here we compared P. aeruginosa
      populations from clinical and environmental samples, both isolated from the
      Bellvitge Hospital of the University of Barcelona in Spain. METHODS: Antibiotic
      susceptibility determination as well as whole cell and outer membrane protein
      denaturing gel electrophoresis, pulsed-field electrophoresis, and random
      amplified polymorphic DNA analysis were performed. RESULTS: Environmental
      isolates were much more susceptible to antibiotics than those isolated from
      clinical specimens. The remainder of the analyses revealed high degree of
      diversity. CONCLUSIONS: Whole-cell proteins, outer-membrane proteins, and pulsed
      field electrophoresis did not support a close relationship between clinical and
      environmental isolates. Random amplified polymorphic DNA (RAPD) confirmed the
      distance between isolates from both sources. This suggests that the origin of
      hospital infections by P. aeruginosa is due mainly to growth of bacterial strains
      acquired by patients prior to hospital admission or from patient-to-patient
      through healthcare workers (HCWs).

PMID- 15163470
TI  - Inverse relationship between decreased infectious diseases and increased
      inflammatory disorder occurrence: the price to pay.

PMID- 15163471
TI  - NTPDase and 5'-nucleotidase activities in rats with alloxan-induced diabetes.
AB  - Diabetes is associated with a hypercoagulable state. In this study, we
      investigated the potential effects of alloxan-induced diabetes on the activities
      of the enzymes NTPDase (E.C. 3.6.1.5, apyrase, ATP diphosphohydrolase, ecto/CD39)
      and 5'-nucleotidase (E.C. 3.1.3.5, CD73) that can control the levels of ADP and
      adenosine, two substances that regulates platelet aggregation. In the alloxan
      treated rats, NTPDase activity was significantly increased by 88 and 35% with ATP
      as substrate and by 156 and 58% with ADP as substrate in platelets and
      synaptosomes, respectively (P< 0.05). AMP hydrolysis was increased by 142%
      (platelets) and 70% (synaptosomes) in diabetic rats compared to control. These
      results demonstrate that alloxan-induced diabetes interferes with ATP, ADP, and
      AMP hydrolysis in platelets and synaptosomes. Taken together, these results may
      indicate that in diabetic rats both NTPDase and 5'-nuleotidase from the central
      nervous system (CNS) and platelets respond similarly with increased activity.
      Thus, we speculate that platelets could be used as a potential peripheral marker
      of central alterations in NTPDase and 5'-nucleotidase activities in diabetes.

PMID- 15163472
TI  - Effect of soluble fiber intake in lipid and glucose levels in healthy subjects: a
      randomized clinical trial.
AB  - OBJECTIVE: The aim of our work was to carry out a randomized clinical trial with
      two diets, one enriched in fiber (total fiber 30 g and soluble fiber 4 g) to
      investigate the effect on lipid and glucose levels in healthy subjects. RESEARCH
      DESIGN AND METHODS: Fifty-three subjects were prospectively randomized to two
      groups (see Table 1). Group I received a diet with 10.4 g of fiber given as 1.97
      g soluble fiber (pectins, gums and mucilages) and 8.13 g of insoluble fiber
      (hemicelullose, cellulose and lignins) and Group II received a diet with 30.5 g
      of fiber of which 4.11 g were soluble fiber and 25.08 g insoluble fiber.
      Prospective serial assessment of weight and nutritional intake (3 days written
      food records) were made. These determinations were performed at baseline and at 3
      months. All enrolled subjects underwent the following examinations; fasting blood
      samples were drawn for measurement of total cholesterol, triglyceride
      concentrations and other lipid fractions, low density lipoprotein (LDL
      cholesterol), high density lipoprotein (HDL-cholesterol), glucose, and insulin.
      RESULTS: Total calorie and fat consumption were lower than recommended in both
      groups (calories; group I 1633+/-417 kcal per day versus group II 1707.5 +/- 579
      kcal per day:ns) and (fats; group I 73.4 +/- 22.7 g per day versus group II [72.6
      +/- 28 g per day:ns), without differences in fatty acid intake profile. Total
      fiber intake did not reach that recommended in both diets but it was higher in
      group II ( 9.06 +/- 2.7 g per day versus 25.95 +/- 7.12 g per day: P < 0.05).
      Soluble fiber intake did not reach that recommended in both diets but it was
      higher in group II (1.7 +/- 0.58 g per day versus 3.5 +/- 0.96 g per day: P <
      0.05). Body weight did not change in both groups during treatment. During
      treatment, in group II a significant change was detected from baseline in LDL
      cholesterol and fasting glucose levels. LDL-cholesterol decreased by 12.8% (P <
      0.05) and glucose decreased by 12.3% (P < 0.05). No statistical differences were
      detected among triglycerides, HDL-cholesterol, and insulin levels. CONCLUSIONS:
      Modest increases in soluble fiber intake in healthy subjects improved LDL
      cholesterol and glucose levels.

PMID- 15163473
TI  - Flow mediated dilatation and carotid intimal media thickness in South Indian type
      2 diabetic subjects.
AB  - OBJECTIVE: The aims of this study were to determine: (1). endothelial function in
      type 2 diabetic subjects with and without diabetic microvascular complications
      using flow mediated dilatation method (FMD); (2). influence of other variables on
      FMD; and (3). the correlation between FMD and carotid intimal media thickness
      (IMT). RESEARCH, DESIGN AND METHODS: In this cross-sectional study, flow mediated
      dilatation (FMD) and intimal media thickness (IMT) were determined using high
      resolution ultrasonography in 20 non-diabetic subjects, in 23 type 2 diabetic
      subjects without any complications and in 23 type 2 diabetic patients with
      nephropathy and retinopathy. RESULTS: Age-adjusted mean (S.D.) FMD value in
      diabetic subjects (8.9 +/- 5%) was lower (P < 0.0001) when compared with the
      group of control subjects (18.8 +/- 7.5 %. However, there was no difference in
      the age-adjusted FMD values between diabetic subjects with and without
      complications (7.3 +/- 3.3 % versus 10.5 +/- 5.9 %). FMD levels did not vary
      significantly between sexes in both non-diabetic and diabetic groups. FMD
      correlated negatively with carotid IMT (r = -0.23, P < 0.05). In multiple linear
      regression analysis, age adjusted FMD was associated only with type 2 diabetes
      with complications (P = 0.012). The variance explained was 21.9%. CONCLUSION:
      Abnormal FMD and increased carotid IMT were present in type 2 diabetes. Both
      these parameters negatively correlated with each other supporting an association
      between impaired FMD and atherogenesis. As these abnormalities existed even in
      diabetic subjects with no microvascular complications, it is likely that they
      preceded the development of these complications.

PMID- 15163474
TI  - The impact of vitamin and/or mineral supplementation on lipid profiles in type 2
      diabetes.
AB  - OBJECTIVE: The purpose of the present study was to assess the impact of Mg + Zn,
      Vitamins C + E, and combination of these micronutrients on serum lipid and
      lipoprotein profiles in type 2 diabetic patients. MATERIALS AND METHODS: In a
      randomized, double-blind, placebo controlled clinical trial, 69 type 2 diabetic
      patients were randomly divided into four groups, each group receiving one of the
      following daily supplement for 3 months; group M: 200 mg Mg and 30 mg Zn (n =
      16), group V: 200mg Vitamin C and 150 mg Vitamin E (n = 18), group MV: minerals
      plus vitamins (n = 17), group P: placebo (n = 18). Fasting blood and urine
      samples were collected at the beginning and at the end of the trial. Serum
      triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-c) and
      low density lipoprotein cholesterol (LDL-c) were measured enzymatically.
      Apolipoproteins (apo) A1 and B were measured by immunoturbidimetric method.
      Adjustment for differences in baselines covariates and changes in variables
      during study were performed by analysis of covariance using general linear
      models. RESULTS: Results indicate that after 3 months of supplementation mean
      serum levels of HDL-c and apo A1 increased significantly in the MV group by 24%
      (50.4 +/-19.3 mg/dl versus 40.6 +/- 10.8 mg/dl) and 8.8% (169.8 +/- 33.8 mg/dl
      versus 156.1+ /- 23.9 mg/dl), respectively (P < 0.01). There were no significant
      changes in the levels of these parameters in the other three groups. Serum levels
      of total cholesterol, LDL-c, triglyceride, and apo B were not altered after
      supplementation in all four groups. CONCLUSION: It is concluded that since co
      supplementation of Mg, Zn, Vitamins C and E significantly increases HDL-c and apo
      A1, supplementation of these micronutrients could be recommended for the type 2
      diabetic patients based on their daily requirements.

PMID- 15163475
TI  - Effect of carbohydrate source on post-prandial blood glucose in subjects with
      type 1 diabetes treated with insulin lispro.
AB  - Our purpose was to determine if the glycemic index (GI) and proportion of
      carbohydrate absorbed as glucose (Pg) affected glycemic responses and occurrence
      of post-prandial hypoglycemia in subjects with type 1 diabetes treated with
      insulin lispro. Subjects (n=8) were studied on five separate occasions after 10
      12 h overnight fasts following a standard dinner. After their morning insulin
      dose, subjects ate 50 g carbohydrate from a starchy food (Pg=1; mashed potato
      GI=83, white bread GI=71, spaghetti GI=41, barley GI=25) or pineapple juice
      (Pg=0.5; GI=46). Blood glucose was measured fasting and at 30 min intervals for 4
      h. Glucose responses after different foods differed significantly from 30 to 180
      min, with mean incremental area under the curve being closely related to GI
      (r=0.98, P<0.01). By multiple regression analysis, occurrence of post-prandial
      hypoglycemia was influenced (P<0.05) by subject and Pg. Time to hypoglycemia was
      affected by subject, fasting glucose, and GI. Thus, in subjects with type 1
      diabetes treated with insulin lispro, GI predicts glycemic responses of
      carbohydrate foods. Pg may affect the occurrence of post-prandial hypoglycemia,
      while GI may affect its timing. Further studies using mixed meals are required to
      confirm how carbohydrate source affects glycemic responses and occurrence of
      hypoglycemia in normal meal setting.

PMID- 15163476
TI  - ACE inhibitors and calcium channel blockers: patterns of use and associations
      with mortality in type 1 diabetes.
AB  - OBJECTIVE: To determine the frequency of ACE-I and Calcium channel blockers (CCB)
      use in type 1 diabetes (T1D), and associations of these medications with
      mortality. RESEARCH DESIGN AND METHODS: Data from the Pittsburgh Epidemiology of
      Diabetes Complications (EDC) Study, a 10-year follow up of childhood onset T1D,
      were used to document ACE-I and CCB use. Use in subjects who died during follow
      up was compared to gender, age, duration (+/-5 years), hypertension, and renal
      status matched living controls. RESULTS: ACE-I use increased from baseline (1986
      1988) to 10 years later (1996-1998) for those with hypertension (20.8-65.8%), and
      microalbuminuria (2.3-31.5%). However, the majority of patients with
      microalbuminuria were not on ACE-I at 10 years. CCB use was 2.1% at baseline,
      increased to 10.4% at 8 years, and fell to 9.5% at 10 years. An increased risk of
      mortality was apparent for those not treated with either ACE-I or CCB when
      controlling for cardiovascular status and age (hazard ratio (HR) 2.6, 95% CI 1.1
      6.3), while ACE-I use alone was protective (HR=0.26, 0.08-0.79). CCB use with or
      without ACE-I was not related to mortality status. CONCLUSIONS: This data
      suggests that ACE-I use is not optimal, but more favorably associated with
      decreased mortality than CCB use.

PMID- 15163477
TI  - Glycohemoglobin (A1C) distribution in school children: results from a school
      based screening program.
AB  - OBJECTIVE: To establish the normal distribution for glycohemoglobin (A1C) in
      sixth and seventh grade children and to assess the practicality of a school-based
      fingerstick screening program. RESEARCH DESIGN AND METHODS: Fingerstick capillary
      whole blood was collected from 400 children aged 11 to 13 years and the percent
      A1C was determined on-site. RESULTS: Among the boys, the A1C was significantly
      higher among the minorities (4.88+/-0.37%, mean+/-S.D.) than among the non
      hispanic whites (4.73+/-0.41%, P<0.01), but was similar in the two groups of
      girls (4.74+/-0.41 and 4.75+/-0.34, respectively, P=0.88). None of the students
      had abnormal glucose tolerance by the standards published for adults.
      CONCLUSIONS: A1C in boys was higher among minorities than among the non-hispanic
      whites, even at this young age of 11-13 years. This may be an early sign of
      predisposition to type 2 diabetes among the groups known to be at higher risk for
      type 2 diabetes. However, this difference was not seen among girls. Reasons for
      the discrepancy between boys and girls is unexplained. A school-based fingerstick
      screening program proved to be practical. As the risk of obesity-related
      diseases, such as type 2 diabetes mellitus, increases among youth, the classroom
      may become an important location for screening.

PMID- 15163478
TI  - Hospitalization and re-hospitalization of people with and without diabetes in La
      Plata, Argentina: comparison of their clinical characteristics and costs.
AB  - OBJECTIVE: To examine the prevalence, characteristics, and costs of
      hospitalization and re-hospitalization of diabetic and non-diabetic patients in
      La Plata, Argentina, and to compare the data with those of developed countries.
      RESEARCH DESIGN AND METHODS: We studied all in-hospital registries of diabetic
      patients enrolled in a health maintenance organization of the Province of Buenos
      Aires (IOMA, November 1996). For each diabetic patient (127 persons), the
      characteristics of two other hospitalized non-diabetic patients matched by age
      and gender were simultaneously recorded. RESULTS: Of the 2200 recorded
      hospitalizations, 5.8% were for diabetic patients, accounting for 10.5% of the
      hospitalization cost. Cardiovascular diseases were the major cause of
      hospitalization in both groups. The per capita hospitalization cost of diabetic
      patients was significantly higher: 1628.5+/-1754.0 US dollars versus 833+/-842 US
      dollars; P=0.00002. Percent re-hospitalizations were five and a half times higher
      in diabetic patients (P=0.0001), and significantly associated with history of
      severe episodes of acute (odds ratio: 3.61; 95% CI: 1.11-11.70; P=0.03) and
      chronic (odds ratio: 4.26; 95% CI: 1.60-11.29; P=0.004) complications.
      CONCLUSIONS: The combination of higher and longer hospitalization rates and
      frequent re-hospitalizations resulted in increased costs for our diabetic
      population. Implementation of care programs based on education (for physicians
      and patients) could effectively decrease current and future costs of the disease.

PMID- 15163479
TI  - Factors affecting hypoglycemia awareness in insulin-treated type 2 diabetes: The
      Diabetes Outcomes in Veterans Study (DOVES).
AB  - OBJECTIVE: To identify clinical factors that affect hypoglycemia perception in
      type 2 diabetes. METHODS: Prospective observational study of 344 insulin-treated
      subjects randomly selected from pharmacy records at three large medical centers.
      At entry, subjects underwent an extensive psychological evaluation and then
      monitored their blood glucoses in their usual fashion for up to 52 weeks using a
      glucose meter capable of storing 1000 readings. For blood glucoses <or=3.33
      mmol/l (60 mg/dl), subjects recorded the severity of symptoms in a log book.
      Symptoms were scored '0' if they were asymptomatic, '1' for symptoms that were
      mild-to-moderate, and '2' if the subject had a diminished level of consciousness
      or required the assistance of others. A mean blood glucose and mean symptom score
      were calculated for all hypoglycemic episodes detected by each patient. RESULTS:
      One hundred seventy-six subjects (51.2%) had a median of 4.5 hypoglycemic events
      during 42.5+/-8.0 weeks of follow-up. The mean hypoglycemic blood glucoses and
      mean symptom scores were modestly correlated (r=0.153; P=0.043). After adjusting
      for blood glucose, symptom scores were lower in the elderly and higher in
      subjects with higher diabetes knowledge scores, microvascular complications, and
      higher entry hemoglobin A1c. Multiple linear regression showed that the latter
      three factors were independently predictive of higher symptoms. CONCLUSIONS:
      Conventional clinical data may be useful in identifying patients with poor
      hypoglycemia perception. Patients with better long- and short-term glycemic
      control are at higher risk and may benefit from instruction on all aspects of
      hypoglycemia.

PMID- 15163480
TI  - Proceedings of the First European Influenza Conference. Malta, 20-23 October
      2002.

PMID- 15163481
TI  - Influence of clinical case definitions with differing levels of sensitivity and
      specificity on estimates of the relative and absolute health benefits of
      influenza vaccination among healthy working adults and implications for economic
      analyses.
AB  - Clinical illness case definitions for influenza and methods used to define
      influenza seasons can vary substantially from study to study. These differences
      often result in differing levels of sensitivity, specificity and positive
      predictive value for the case definitions used. We explored the implications of
      different case definitions and outcome periods on estimates of influenza vaccine
      effectiveness and cost benefit by conducting additional analyses of data
      collected from a randomized, double blind, placebo controlled trial of the
      trivalent, intranasal, live attenuated influenza virus vaccine in healthy working
      adults. Febrile upper respiratory tract illnesses occurring during the peak
      influenza period was identified as the most specific clinical case definition
      expected to have the highest positive predictive value for true influenza whereas
      events occurring on a day with any symptom occurring during the entire outcome
      period was identified as the most sensitive clinical case definition with the
      lowest positive predictive value for influenza. As expected, the former provided
      the highest estimates of vaccine effectiveness (28.4% reduction in work loss
      days, 24.6% reduction in days with impaired productivity and 40.9% reduction in
      days with health care provider visits) but the lowest estimates of absolute
      reductions in events (42.4 work loss days prevented per 1000, 79.0 impaired
      productivity days per 1000, and 16.5 days with health care provider visits per
      1000). On the other hand, events on days with any symptom during the entire
      outcome period provided the lowest estimates of vaccine effectiveness (18%
      reduction in work loss days, 18% reduction in days with impaired productivity,
      and 13% reduction in days with health care provider visits) but the highest
      estimates of absolute reductions in events (186.4 work loss days per 1000, 271.5
      impaired productivity days per 1000, and 44.8 days with health care provider
      visits per 1000). When applied to a cost benefit analysis, the more specific case
      definition provided a break even cost for vaccination of US$ 6.58 whereas the
      more sensitive case definition provided a break even cost for vaccination of US$
      43.07. Clearly the latter combination is most appropriate when trying to assess
      the total population level impact of a vaccine preventable disease and the
      potential cost effectiveness of vaccination whereas the former may be most
      appropriate for assessing whether the vaccine actually works. The definitions of
      clinical influenza illness and outcome periods should be selected to match the
      study question.

PMID- 15163482
TI  - Modeling pandemic preparedness scenarios: health economic implications of
      enhanced pandemic vaccine supply.
AB  - Influenza pandemic planning is a complex, multifactorial process, which involves
      public health authorities, regulatory authorities, academia and industry. It is
      further complicated by the unpredictability of the time of emergence and severity
      of the next pandemic and the effectiveness of influenza epidemic interventions.
      The complexity and uncertainties surrounding pandemic preparedness have so far
      kept the various stakeholders from joining forces and tackling the problem from
      its roots. We developed a mathematical model, which shows the tangible
      consequences of conceptual plans by linking possible pandemic scenarios to health
      economic outcomes of possible intervention strategies. This model helps to
      structure the discussion on pandemic preparedness and facilitates the translation
      of pandemic planning concepts to concrete plans. The case study for which the
      model has been used shows the current level of global pandemic preparedness in an
      assumed pandemic scenario, the health economic implications of enhanced pandemic
      vaccine supply and the importance of cell culture-based influenza vaccine
      manufacturing technologies as a tool for pandemic control.

PMID- 15163484
TI  - Medical economics in the field of influenza--past, present and future.
AB  - Influenza represents a major challenge for public health worldwide. The burden of
      suffering is not only reflected by the extent of hospitalisations and deaths
      arising from this devastating disease, but also by the attributed economic toll.
      The economics of this disease can, however, be changed favourably due to the
      availability of efficacious vaccines. Recent studies have demonstrated the
      economic benefits of vaccinating not only persons at risk, but also healthy
      working adults. There seems to be an economic advantage even in immunising
      certain pediatric subpopulations. Only with a clear and transparent body of
      economic evidence will it be possible to advise health authorities and payors on
      the utility of influenza vaccination vaccination policies.

PMID- 15163483
TI  - The expected number of hospitalisations and beds needed due to pandemic influenza
      on a regional level in the Netherlands.
AB  - In order to minimise the effects of a potential influenza pandemic on the
      population, regional authorities in the Netherlands are in the process of
      development of a plan to be prepared to cope with mass illness and to ensure
      health care services. The objective of this study is to calculate the expected
      numbers of hospitalisations and the maximum number of beds needed per day on a
      regional level. As many uncertainties are involved in this type of studies, we
      have performed a scenario analysis of the expected number of hospitalisations and
      beds needed during an influenza pandemic. The analysis gives insight into the
      impact of the pandemic in terms of how many will be hospitalised, how many beds
      are needed during the pandemic and in the effect of a possible intervention by
      therapeutic use of antivirals in terms of hospitalisations and beds needed. It
      can be concluded that our scenario analysis will be helpful in designing and
      planning on a regional level.

PMID- 15163485
TI  - Harmonising the virological surveillance of influenza in Europe: results of an 18
      country survey.
AB  - The European influenza surveillance scheme (EISS) is based on a surveillance
      model that combines clinical and virological data in the general population.
      Eighteen countries in Europe report weekly influenza activity to EISS
      (http://www.eiss.org). A questionnaire on the virological data collection was
      sent electronically to the EISS members. Questions on the specimen collection,
      representativity, laboratory diagnosis of influenza, reporting of variants,
      testing for other respiratory infections, serological testing, near-patient tests
      and preparedness for a pandemic were included. The results of the survey showed
      that for the typing of influenza, the methods polymerase chain reaction (PCR),
      enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition (HAI)
      methods are used most frequently. For the subtyping of influenza, HAI and PCR are
      used most often. An east-west divide was seen for the use of PCR in typing and
      subtyping (more PCR use in the west). Differences in the virological surveillance
      systems in Europe can make direct comparisons difficult because detection rates
      may differ by test. For the reporting of other respiratory infections besides
      influenza, many networks (68%) collect information on RSV. This is important
      because RSV causes similar clinical symptoms as influenza and can have a similar
      impact in terms of burden of disease. With the collection of RSV data, EISS is
      moving to a broader spectrum of viral respiratory diseases. The findings of this
      survey will be used to better harmonise laboratory methods in EISS in order to
      obtain more reliable and comparable information on influenza activity in Europe.

PMID- 15163487
TI  - Recent changes among human influenza viruses.
AB  - Recurrent epidemics of influenza are due to the frequent emergence of antigenic
      variants. With co-circulation of two influenza A subtypes and two antigenically
      distinct lineages of B viruses, genetic reassortment also has an important role
      in antigenic drift, as illustrated by recent changes in both A and B viruses. The
      H1N2 subtype viruses, which emerged during 2001, possessed a H1 HA similar to
      those of contemporary A/New Caledonia/20/99 (H1N1)-like viruses and seven genes
      closely related to those of recent H3N2 viruses, and did not represent a
      significant increase in the antigenic diversity of circulating viruses. The re
      emergence of B/Victoria/2/87-lineage viruses, previously prevalent during the
      1980s, in 2000 has been followed by the predominant circulation of reassortant B
      viruses possessing a B/Victoria-lineage HA and a B/Yamagata-lineage NA similar in
      sequence to those of recent B/Sichuan/379/99-like viruses. These events emphasize
      not only the lack of divergence in the complementary functional characteristics
      of the HA and NA of divergent influenza B lineages, but also the apparent
      convergence in compatibility between the H1 and N2 components of the two
      influenza A subtypes.

PMID- 15163486
TI  - Are influenza surveillance data useful for mapping presentations?
AB  - Geographical information system (GIS) based on mappings of influenza data are
      rare (http://www.b3e.jussieu.fr.80/sentiweb/fr) and influenza data are commonly
      aggregated for rather large areas (http://www.eiss.org,
      http://oms2b3e.jussieu.fr/FluNet). The most limiting factors for the use of
      morbidity-data from practices in GIS-based mappings are differences which are not
      related to morbidity. These differences may be due to consultation behaviour,
      interpretation of the case definition, age distribution of patients and other
      reasons. In order to reduce the impact of these non-morbidity related differences
      on the interpretation, the data of many practices are usually pooled and
      consequently rather large areas are presented. Extracting and harmonising the
      signals for increased morbidity from practices is a presupposition for mapping
      with a sufficient geographical resolution. The possibility to harmonise by
      reducing those confounding differences on a practice level is investigated.
      Different harmonisation methods were applied to data from Germany where acute
      respiratory infections (ARI) per consultations are registered and from The
      Netherlands were influenza like illnesses (ILI) per population are registered.
      The harmonisation of the indices between countries was achieved by scaling them
      in relation to the level of the index representative for the peak activity during
      a usual influenza epidemic. The Kriging method is applied as a means of spatial
      prediction for the influenza data. The preliminary results are discussed with
      respect to resulting mappings.

PMID- 15163488
TI  - Epidemiological features of a new strain of the influenza A virus--influenza A
      (H1N2) circulating in England and its public health implications.
AB  - The UK influenza season of 2001/2002 was characterized by widespread geographic
      circulation of a new subtype of influenza A (H1N2) virus throughout the duration
      of the season. Younger children were predominantly infected, suggesting primary
      infection. Despite this, the public health impact of this new virus was minimal.
      It remains to be seen whether influenza A (H1N2) virus will persist and co
      circulate with the previously circulating subtypes of influenza A (H1N1 and
      H3N2), or whether it was a sporadic recombination event that will disappear.
      Ultimately, the emergence of a new strain highlights the importance of continual
      surveillance of circulating viruses.

PMID- 15163489
TI  - Reassortment and evolution of current human influenza A and B viruses.
AB  - During the 2001-2002 influenza season, human influenza A (H1N2) reassortant
      viruses were detected globally. The hemagglutinin (HA) of these H1N2 viruses was
      similar to that of the A/New Caledonia/20/99 (H1N1) vaccine strain both
      antigenically and genetically, while their neuraminidase (NA) was antigenically
      and genetically related to that of recent human influenza H3N2 reference viruses
      such as A/Moscow/10/99. All six internal genes of the H1N2 reassortants
      originated from an H3N2 virus. After being detected only in eastern Asia during
      the past 10 years, Influenza B/Victoria/2/87 lineage viruses reappeared in many
      countries outside of Asia in 2001. Additionally, reassortant influenza B viruses
      possessing an HA similar to that of B/Shandong/7/97, a recent B/Victoria/2/87
      lineage reference strain, and an NA closely related to that of B/Sichuan/379/99,
      a recent B/Yamagata/16/88 lineage reference strain, were isolated globally and
      became the predominant influenza B epidemic strain. The current influenza vaccine
      is expected to provide good protection against H1N2 viruses because it contains
      A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) like viruses whose H1 HA
      or N2 NA are antigenically similar to those of recent circulating H1N2 viruses.
      On the other hand, widespread circulation of influenza B Victoria lineage viruses
      required inclusion of a strain from this lineage in influenza vaccines for the
      2002-2003 season.

PMID- 15163490
TI  - Phylogenetic studies of influenza B viruses isolated in southern Africa: 1998
      2001.
AB  - Influenza B viruses isolated in southern Africa during the period from 1998 to
      2001 were analysed by sequence analysis of the viral haemagglutinin HA1 subunit
      and the phylogenetic relationships were determined. Influenza B activity varied
      considerably in South Africa during the 4-year study period with no activity
      detected in 2000. Phylogenetic analysis revealed that viruses isolated in 1998
      from a localised outbreak in Durban belonged to two distinct sub-lineages. Some
      of the influenza B viruses isolated throughout South Africa in 1999 as well as
      several viruses obtained from Mozambique in the same year were closely related to
      the B/Yamanashi/166/98-like viruses. In contrast, the majority of the 1999
      isolates, represented by B/Johannesburg/5/99, exhibited considerable drift from
      the B/Yamanashi/166/98 stain. The viruses isolated during the 2001 season fell
      into two sub-lineages, one of which had evolved from the B/Johannesburg/5/99-like
      viruses and the other which had evolved from the group of viruses that included
      one of the 1998 Durban isolates. These molecular epidemiological studies reveal a
      diverse and complex pattern of influenza B virus strains circulating in southern
      Africa.

PMID- 15163491
TI  - Multiple lineages of antigenically and genetically diverse influenza A virus co
      circulate in the United States swine population.
AB  - Before the isolation of H3N2 viruses in 1998, swine influenza in the United
      States was an endemic disease caused exclusively by classical-swine H1N1 viruses.
      In this study we determined the antigenic and phylogenetic composition of a
      selection of currently circulating strains and revealed that, in contrast to the
      situation pre-1998, the swine population in the United States is now a dynamic
      viral reservoir containing multiple viral lineages. H3N2 viruses still circulate
      and representatives of each of two previously identified phylogenetic groups were
      isolated. H1N1 and H1N2 viruses were also identified. In addition to the
      genotypic diversity present, there was also considerable antigenic diversity
      seen. At least three antigenic profiles of H1 viruses were noted and all of the
      recent H3N2 viruses reacted poorly, if at all, to the index A/swine/Texas/4199
      2/98 H3N2 antiserum in hemagglutination inhibition assays. The influenza
      reservoir in the United States swine population has thus gone from a stable
      single viral lineage to one where genetically and antigenically heterogenic
      viruses co-circulate. The growing complexity of influenza at this animal-human
      interface and the presence of viruses with a seemingly high affinity for
      reassortment makes the United States swine population an increasingly important
      reservoir of viruses with human pandemic potential.

PMID- 15163492
TI  - Influenza-associated acute encephalopathy in Japanese children in 1994-2002.
AB  - We addressed the incidence of influenza-associated acute encephalopathy, which is
      distinct from Reye syndrome, in children in Japan. Eighty-nine children with a
      mean age of 3.8 years were reported to have developed this disease during eight
      influenza seasons (December 1994-April 2002) in Hokkaido, Japan. None of them had
      received aspirin. Most of the patients rapidly became comatose with or without
      convulsions with a mean interval of 1.7 days from the onset of fever to the onset
      of central nervous system symptoms. Thirty-three (37.1%) patients died and 17
      (19.1%) patients had neurological sequelae. A total of 53 (59.6%) cases were
      proved to have an influenza virus infection. Interleukin-6 and tumor necrosis
      factor-alpha were markedly elevated in serum and cerebrospinal fluid samples from
      two patients who died after a rapid, fulminant course. A post-mortem examination
      of one fatal case revealed vasogenic brain edema with generalized vasculopathy,
      suggesting that the generalized impairment of vascular endothelial cells caused
      by highly activated cytokines plays a central role in the pathophysiology of this
      disease. We conclude that influenza-associated acute encephalopathy may be an
      underestimated syndrome and is another reason to promote vaccination against
      influenza in infants and younger children.

PMID- 15163493
TI  - A novel means of identifying the neuraminidase type of currently circulating
      human A(H1) influenza viruses.
AB  - With the recent emergence and spread of influenza A(H1N2) viruses which appear to
      have arisen by reassortment of circulating A(H1N1) and A(H3N2) strains, there is
      a need in epidemiological studies to determine the neuraminidase type in order to
      differentiate between influenza A(H1N2) and A(H1N1) strains. A fluorescence-based
      neuraminidase enzyme inhibition assay that has been developed to screen influenza
      viruses for potential resistance to the neuraminidase inhibitor drugs appears to
      be suitable for this purpose. When used with the neuraminidase inhibitor
      zanamivir the assay was able to provide a positive predictive value of 93.5% for
      the identification of neuraminidase type N1 or N2. This assay enables a large
      number of influenza A viruses to be screened at low cost to determine relative
      levels of A(H1N2) or A(H1N1) viruses circulating in the population.

PMID- 15163494
TI  - Detection of influenza B in clinical specimens: comparison of high throughput RT
      PCR and culture confirmation.
AB  - Influenza virus is one of the major causes of worldwide respiratory tract
      infections during the winter season. Here we describe a high throughput (HTP)
      protocol for rapid diagnosis of influenza B that combines automated viral RNA
      extraction with detection and quantification by TaqMan-based PCR. Using this
      methodology, we tested 4176 nasal swabs collected from children enrolled in a
      European influenza vaccine trial during the winter of 2000 to compare our HTP PCR
      method to culture confirmation for detection of influenza B. Among these, 37 were
      positive by culture and 169 were positive by PCR irrespective of virus copy
      number. However, when specimens with fewer than 20 copies of the viral genome
      were disregarded, a good correlation between two methods was observed. At this
      cut-off, 34 specimens were positive and 4106 were negative by both methods.
      Statistical analysis of the data using culture confirmation as the standard
      indicated that the sensitivity of HTP RT-PCR for influenza B was 92% (95% CI,
      0.83-1), and the specificity was 99% (95% CI, 0.99-1). In summary, HTP RT-PCR was
      proved to be more rapid and sensitive than culture confirmation, and it
      correlated significantly with culture confirmation for specimens containing more
      than 20 copies of the viral genome.

PMID- 15163495
TI  - Detection of anti-H5 responses in human sera by HI using horse erythrocytes
      following MF59-adjuvanted influenza A/Duck/Singapore/97 vaccine.
AB  - Haemagglutination-inhibition (HI) tests are a simple method used to assess immune
      responses to influenza haemagglutinin. However, HI tests are insensitive at
      detection of antibody responses to avian haemagglutinin after vaccination or
      natural infection, even in the presence of high titres of neutralising antibody
      or virus isolation. Avian influenza viruses preferentially bind to sialic acid
      receptors that contain N-acetylneuraminic acid alpha2,3-galactose (alpha2,3Gal)
      linkages while human viruses preferentially bind to those containing N
      acetylneuraminic acid alpha2,6-galactose (alpha2,6Gal) linkages. By using horse
      erythrocytes in the HI test and thereby increasing the proportion of alpha2,3Gal
      linkages available for binding, we are able to demonstrate improved detection of
      antibody to avian H5 in human sera following vaccination with MF59-adjuvanted
      A/Duck/Singapore/97 surface antigen vaccine. This modified HI test was more
      sensitive in detection of anti-H5 antibody evoked by revaccination of primed
      subjects and may be useful in assessing potential avian HA vaccine candidates.

PMID- 15163496
TI  - Sequence variation in the influenza A virus nucleoprotein associated with escape
      from cytotoxic T lymphocytes.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) contribute to the control of viral infections
      by recognizing peptides of viral proteins presented by MHC class I molecules on
      infected cells. Some viruses have developed strategies to evade recognition by
      CTL. One of these strategies involves antigenic variation in CTL epitopes as
      described for viruses chronically infecting their host like EBV, HIV, HBV and
      HCV. Here we show three examples of variation in CTL epitopes in the influenza
      virus nucleoprotein (NP) associated with escape from CTL immunity. The first two
      involve a mutation at position 384 of the NP, which is the anchor residue of a
      HLA-B*2705-restricted epitope NP383-391 (SRYWAIRTR) and the HLA-B*08-restricted
      epitope NP380-388 (ELRSRYWAI). It was shown that these mutations have arisen in
      the 1993/1994 season and that these mutant variants completely replaced the virus
      strains containing the wild-type epitopes. Furthermore, T cell recognition was
      completely abrogated by the R384G mutation. A third example of variation in an
      influenza virus CTL epitope was found in a newly identified HLA-B*3501-restricted
      CTL epitope. This immunodominant epitope exhibited extensive amino acid sequence
      variation and the variants emerged in a chronological order. Again CTL specific
      for older variants failed to recognize more recent strains of influenza A virus,
      indicating an escape from CTL immunity. Thus, in addition to the introduction of
      mutations in the surface glycoproteins like the hemagglutinin, allowing escape
      from antibody-mediated immunity, there is now evidence that influenza viruses can
      escape in a similar way from CTL-mediated immunity.

PMID- 15163497
TI  - Exploring cross-protection between influenza strains by an epidemiological model.
AB  - Almost all influenza surveillance systems of temperate countries report a single
      influenza illness peak each winter. Although several strains of different types
      or subtypes may co-circulate, they exceptionally lead to two distinct illness
      peaks during the same winter. We hypothesize that cross-protection between the
      different strains can, by itself, explain this absence of succeeding illness
      peaks. We used a dynamic population model to describe the spread of two influenza
      strains during one season. Cross-protection is included through a parameter
      defined as the reduction of host risk of infection to one strain after infection
      with another strain. Different scenarios are performed with two strains emerging
      with different time-lags, for different levels of cross-protection. We show that
      a cross-protection of 50% between the two strains is sufficient to explain why we
      observe a single influenza illness peak in temperate countries.

PMID- 15163498
TI  - The NS1 gene of H5N1 influenza viruses circumvents the host anti-viral cytokine
      responses.
AB  - The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent,
      but the mechanism of their virulence in humans is largely unknown. Here we show
      that lethal H5N1 influenza viruses, unlike other human, avian, and swine
      influenza viruses, are resistant to the anti-viral effects of interferons and
      tumor necrosis factor alpha The nonstructural (NS) gene of H5N1 viruses is
      associated with this resistance. Pigs infected with recombinant human H1N1
      influenza virus that carried the H5N1 NS gene experienced significantly greater
      and more prolonged viremia, fever, and weight loss than did pigs infected with
      wild-type human H1N1 influenza virus. These effects required the presence of
      glutamic acid at position 92 of the NS1 molecule. These findings may explain the
      mechanism of the high virulence of H5N1 influenza viruses in humans and provide
      insight into the virulence of 1918 Spanish influenza.

PMID- 15163499
TI  - Genetic relationships, serological cross-reaction and cross-protection between
      H1N2 and other influenza A virus subtypes endemic in European pigs.
AB  - This study examines the genetic relationships between the recently emerged H1N2
      swine influenza virus and viruses of H1N1 and H3N2 subtypes, and the extent of
      protection against H1N2 challenge in pigs immune after infection or vaccination
      with the other subtypes. There was low amino acid homology (70.4-71.9%) in the
      haemagglutinin (HA) gene between H1N1 viruses used for primary infection or
      vaccination and the H1N2 challenge strain, with 94-99 amino acid changes between
      these viruses involving all five antigenic sites. The NA genes of H3N2 viruses
      used for primary infection or vaccination showed higher amino acid homology with
      H1N2 (88.3-92.6%), while nucleoprotein (95.5-96.3% nucleotide identity) and
      matrix (96.8-98.4%) genes were most conserved between the three subtypes. Pigs
      immune as a result of intranasal inoculation with either H1N1 or H3N2 showed
      partial clinical protection against H1N2 challenge, and nasal virus excretion was
      2 days shorter than in naive pigs. Moreover, dually infected (H1N1 + H3N2)-immune
      pigs showed complete clinical protection and H1N2 virus replication in the lungs
      and nasal secretions was either undetectable or markedly reduced. In contrast, a
      double vaccination with a commercial H1N1 and H3N2-based vaccine did not protect
      against H1N2 challenge. Haemagglutination inhibition (HI) or virus neutralisation
      (VN) tests of swine sera revealed little if any antigenic cross-reactivity
      between subtypes. These data suggest that serum HI or VN antibodies are not
      essential in heterosubtypic protection, but that mucosal or cellular immunity are
      probably involved. It is still unknown whether this type of cross-subtype
      protection will also occur in infection-immune pigs in the field.

PMID- 15163500
TI  - Seroprotection rate, mean fold increase, seroconversion rate: which parameter
      adequately expresses seroresponse to influenza vaccination?
AB  - Serological parameters intend to describe antibody response to influenza vaccine
      in a population. However, there is uncertainty about the mathematical
      appropriateness and the biological or clinical meaning of conventionally used
      parameters. Theoretical considerations and exploration of a data-set of 16
      studies with an inactivated (subunit) influenza vaccine involving 1176 adult
      subjects suggest the following conclusions. In a population seronegative before
      vaccination, the post-vaccination geometric mean titre (post-GMT) is a meaningful
      immunological parameter adequately expressing antibody response after
      vaccination. The related protection rate (PR) is a good surrogate parameter for
      protection provided by a given vaccine, thus relevant to public health. However,
      in a population partially seropositive before vaccination (due to previous
      exposition to influenza antigens), the same parameters may, under certain
      conditions, seriously overestimate the antibody response, as they do not account
      for the pre-vaccination state. Conventional attempts to address pre-vaccination
      antibody are associated with either loss of information (exclusion of
      seropositive subjects) or incomplete control of pre-vaccination state (mean fold
      increase (MFI), response rate (RR)). Although not devoid of theoretical
      limitations (heteroscedasticity), correction of post-GMT and PR by linear
      regression appears to provide better estimates of antibody response and vaccine
      immunogenicity.

PMID- 15163501
TI  - Immunogenicity and protective efficacy of influenza vaccination.

PMID- 15163502
TI  - Virosomal influenza vaccine: a safe and effective influenza vaccine with high
      efficacy in elderly and subjects with low pre-vaccination antibody titers.
AB  - In 14 clinical studies, various efficacy and safety aspects of a new virosomal
      influenza vaccine (Invivac) were assessed in 2865 subjects. The virosomal
      influenza vaccine fully complies with the Committee for Proprietary Medicinal
      Products (CPMP) requirement for immunogenicity of influenza vaccines. In
      particular, in a subset of subjects with low pre-vaccination titers (thus those
      persons who actually need protection by a vaccine), between 76 and 99% of
      subjects (dependent on age, health status and vaccine components) achieved
      protective hemagglutination inhibiting (HI) antibody titers after vaccination
      with the virosomal influenza vaccine. Acceptable frequencies of well-known local
      and systemic reactions were observed in healthy adults and risk subjects in
      clinical studies and in a post-marketing study population. These reactions were
      transient and generally not severe, and did not cause major inconvenience. In
      conclusion, Invivac is an efficacious and safe vaccine for the protection against
      influenza in healthy and chronically ill adult subjects. The vaccine is
      especially efficacious in subjects with low pre-vaccination immunity.

PMID- 15163503
TI  - Epidermal powder immunization: cellular and molecular mechanisms for enhancing
      vaccine immunogenicity.
AB  - Epidermal powder immunization (EPI) of mice with an influenza vaccine elicited
      consistently a higher hemagglutination inhibition (HI) antibody titers than
      intramuscular (IM) injection using the same dose of vaccine. The epidermal
      Langerhans cells (LCs) at the site of EPI were found to play an important role in
      the immune responses. Indeed, depletion of LCs from the immunization site prior
      to EPI caused a significant reduction in the antibody response. Transfer of LCs
      isolated from the EPI sites to naive mice induced a robust antigen-specific
      antibody response. Cytokines produced by target site cells appear to be important
      for the augmented immune responses induced by EPI. LTR72, a genetically
      detoxified heat-labile toxin from Escherichia coli with a strong adjuvant effect
      in EPI, was found to bind the keratinocytes of the epidermis, but not the LCs,
      and caused the production of elevated TNF-alpha and IL-12 cytokines in emigrating
      epidermal cells. These results have important implications for the development of
      a more efficacious human influenza vaccine.

PMID- 15163504
TI  - Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA
      fragments.
AB  - A reverse genetics system for the generation of influenza virus A/PR/8/34 (NIBSC
      vaccine strain) from plasmid DNA was developed. Upon transfection of eight
      bidirectional transcription plasmids encoding the gene segments of A/PR/8/34 into
      293T cells, virus titers in the supernatant were about 10(4) TCID50/ml. The
      production of A/PR/8/34 in 293T cells was compared to that of A/WSN/33, for which
      virus titers in the supernatant were 10(7)-10(8) TCID50/ml. Time-course analysis
      of virus production indicated that the differences in virus titers were due to
      reinfection of 293T cells by A/WSN/33 but not A/PR/8/34. Indeed, virus titers of
      A/PR/8/34 comparable to those of A/WSN/33 were achieved upon addition of trypsin
      to the culture medium of transfected cells. The production of chimeric viruses
      revealed that the difference in virus titers between A/PR/8/34 and A/WSN/33 are
      determined primarily by differences in the surface glycoproteins hemagglutinin
      and neuraminidase and the polymerase protein PB1. In conclusion, high-titer virus
      stocks of recombinant influenza A/PR/8/34 virus can be produced as well as virus
      stocks with much lower titers, but without the requirement of virus amplification
      through replication.

PMID- 15163505
TI  - Immunogenicity of a monovalent, aluminum-adjuvanted influenza whole virus vaccine
      for pandemic use.
AB  - In the case of an influenza pandemic a significant gap between influenza vaccine
      manufacturing capacities and vaccine demands must be expected on a global scale.
      This study explores the possibility to increase the number of vaccine doses that
      can be provided with the existing resources by using a lower amount of antigen
      per dose in an aluminum-adjuvanted whole virus vaccine formulation, instead of
      the standard dosage of 15 microg hemagglutinin (HA). The study was performed as
      an open, non-controlled, randomized, multicentric study in 200 volunteers (18-30
      years of age). Three monovalent aluminum-adjuvanted whole virus formulations with
      different antigen concentrations (1.9, 3.75 and 7.5 microg HA per dose) were
      compared to a split virus vaccine (15 microg HA per dose) without aluminum
      adjuvantation. The sera were tested for hemagglutination inhibition (HI)
      antibodies, neuraminidase inhibition (NI) antibodies and virus neutralizing (VN)
      antibodies. Nasal swab samples were tested for influenza-specific IgA antibodies.
      All volunteers were immunologically naive to the vaccine strain influenza
      A/Singapore/1/57 (H2N2). The vaccine was well tolerated. HI titers reached
      protective levels (geometric mean titer (GMT) >1:40) after two vaccine doses. In
      the group immunized with the lowest antigen dose the seroprotection rate was 82%.
      Although the immune response tends to be lower for vaccine formulations with
      reduced antigen content, the immunogenicity criteria as defined by the European
      Agency for the Evaluation of Medicinal Products (EMEA) were met with all antigen
      formulations after two vaccine doses. Significant increases in HI, NI and VN
      titers were observed, however, no significant local immune response was detected.
      The use of a low-dose whole virus influenza vaccine, adjuvanted with aluminum
      appears to be a viable approach to increase vaccine supplies in a pandemic
      situation.

PMID- 15163506
TI  - A "universal" human influenza A vaccine.
AB  - We have previously reported on a universal human influenza A vaccine, based on
      the external domain of the transmembrane viral M2-protein (M2e) [Nature Medicine
      5 (1999) 1119]. M2-protein is scarcely present on the virus but is abundantly
      expressed on virus-infected cells. The external domain, M2e, is 23-amino acids
      long and as such weakly immunogenic. But when presented on an appropriate
      carrier, such as hepatitis B virus core (HBc) particles, it induces a high titer
      antibody response that in mice effectively protects against a potentially lethal
      influenza infection. The advantage of M2e as an antigen is the conservation of
      its sequence that has hardly changed since the first influenza virus was isolated
      in 1933, despite numerous epidemics and several pandemics. Various constructs,
      e.g. M2e fused at the N-terminus of the HBc subunit or inserted in the immuno
      dominant loop, were evaluated as a vaccine. They conferred full protection when
      administered together with an adjuvant. Several adjuvants were tested in
      conjunction with intraperitoneal vaccine administration, while the non-toxic
      enterotoxin mutant LT(R192G) was used for intranasal vaccination. Appropriate
      combinations of vaccine construct and adjuvant allowed to obtain anti-M2e IgG2a
      serum titers above 10,000, and this provided complete protection.

PMID- 15163507
TI  - Current status of live attenuated influenza virus vaccine in the US.
AB  - The efficacy and effectiveness of cold adapted live attenuated (CAIV-T, FluMist
      intranasal influenza vaccine is reviewed. CAIV-T consists of approximately 10(7)
      TCID50 per dose of each influenza A/H1N1, influenza A/H3N2, and influenza B
      vaccine strain. The exact strains are updated each year to antigenically match
      the antigens recommended by national health authorities for inclusion in the
      vaccine. In one year in which the vaccine strain did not well match the epidemic
      strain, the live attenuated vaccine induced a broad immune response that cross
      reacted significantly with the drifted strain. The efficacy of CAIV-T in adults
      was demonstrated with challenge studies and the effectiveness of the vaccine for
      reducing febrile upper respiratory illness, days of missed work, and days of
      antibiotic use was demonstrated in a large field trial. In young children,
      protective efficacy against culture confirmed influenza was demonstrated in a
      field trial with overall protective efficacy of 92% during a two year study.
      Vaccine was also highly protective against a strain not contained in the vaccine,
      with 86% protective efficacy demonstrated against this significantly drifted
      virus. Effectiveness measures, including protection against febrile otitis media
      and visits to the doctor were demonstrated. Live attenuated vaccine provides a
      significant new tool to help prevent influenza.

PMID- 15163508
TI  - Live cold-adapted influenza A vaccine produced in Vero cell line.
AB  - The African green monkey kidney (Vero) cell line was used as a substrate for the
      development of a live cold-adapted (ca) reassortant influenza vaccine. For that
      purpose, a new master strain was generated by an adaptation of the wild type (wt)
      A/Singapore/1/57 virus to growth at 25 degrees C in a Vero cell line. The
      resulting cold-adapted (ca) muster strain A/Singapore/1/57ca showed temperature
      sensitive (ts) phenotype and was attenuated in animal models and protective in
      the challenge experiments in ferrets. Two vaccine candidates of influenza A(H1N1)
      and A(H3N2) subtypes (6/2 reassortants) inheriting six genes coding internal
      proteins from the new master strain and the surface antigens hemagglutinin (HA)
      and neuraminidase (NA) from the epidemic viruses were obtained by a standard
      method of genetic reassortment. All steps of the vaccine preparation were done
      exclusively in Vero cells, including the isolation of the epidemic viruses. Both
      vaccine strains were used for immunization of young adult volunteers in a limited
      clinical trial and appeared to be safe, well tolerated and immunogenic after
      intranasal administration.

PMID- 15163509
TI  - Surveillance of influenza isolates for susceptibility to neuraminidase inhibitors
      during the 2000-2002 influenza seasons.
AB  - Neuraminidase (NA) inhibitors (NI) have recently been licensed for the
      prophylaxis and treatment of influenza virus infection in humans. This study has
      utilized a new chemiluminescent (CL) neuraminidase assay to routinely monitor
      more than a thousand influenza field isolates collected worldwide during the 2000
      2002 seasons for susceptibility to both licensed NIs, zanamivir, and oseltamivir
      by determining the 50% inhibitory concentration (IC50). Our data demonstrated
      that influenza A viruses of the N2 subtype were less susceptible to zanamivir,
      but not oseltamivir, than those of the N1 subtype such that 41 of 45 confirmed
      H1N2 isolates could be reliably differentiated from H1N1 viruses based on their
      zanamivir susceptibility. Pre-titration of influenza A viruses appeared to have
      no effect on IC50 determined for either NI, while pre-titration of influenza B
      viruses significantly reduced oseltamivir IC50 and increased zanamivir IC50.
      Influenza B viruses were less susceptible to either compound than type A
      isolates. The CL assay is a rapid and reliable method for screening large numbers
      of influenza isolates for NI susceptibility. Reassortant viruses of the H1N2
      subtype that started to circulate worldwide during the 2001-2002 season can be
      reliably separated from H1N1 viruses based on their zanamivir susceptibility,
      enabling large scale screening of H1 isolates for determining the prevalence of
      such reassortants.

PMID- 15163510
TI  - Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors.
AB  - A wide use of inhibitors of influenza virus neuraminidase (NAIs) to control
      influenza in humans demands a better understanding of the mechanisms involved in
      the resistance emergence. In vitro studies demonstrate that both neuraminidase
      (NA) and hemagglutinin (HA) influence virus susceptibility to NAIs. Drug
      resistance conferred due to changes in the NA could be monitored in the NA
      inhibition assays. Zanamivir-selected viruses acquired the NA substitutions at
      residues 119 and 292; oseltamivir-selected--at 274 and 292; peramivir-selected-
      at 292; and A-315675-selected--at 119. The HA binding efficiency and therefore
      susceptibility to NAIs are affected by the amino acids forming the HA receptor
      binding site, the location and number of oligosaccharide chains, and structure of
      the neuraminic acid-containing cellular receptors. The lack of suitable cell
      culture-based assays hampers the assessment of virus susceptibility in humans.
      Emergence of the viruses with the NAI-induced substitutions in the NA is uncommon
      in drug-treated humans, however a compromised state of the immune system promotes
      emergence of drug resistance. In vivo, the zanamivir-selected mutant contained a
      substitution at 152 (B/NA); the oseltamivir-selected mutants-at residues 119
      (A/N2), 198 (B/NA), 274 (A/N1), and 292 (A/N2). Substitutions in the NA were
      often accompanied by impairment of virus infectivity and virulence in animal
      models. Because of complexity of mechanisms of virus resistance, further analysis
      of the viruses recovered from the drug-treated humans is warranted.

PMID- 15163511
TI  - Identification of a human influenza type B strain with reduced sensitivity to
      neuraminidase inhibitor drugs.
AB  - A total of 126 influenza B isolates isolated between 1998 and 2002 from
      Australasia and the Asia-Pacific region were tested for their sensitivity to the
      neuraminidase (NA) inhibitor drugs zanamivir and oseltamivir carboxylate using a
      fluorescence-based enzyme assay. The mean (+/-1 S.D.) 50% inhibitory
      concentration (IC50) of the influenza B viruses tested was 1.41+/-0.53 nM against
      zanamivir and 14.91+/-14.31 nM with oseltamivir carboxylate. However, a single
      type B isolate (B/Perth/211/2001) from an infant who had not been treated with
      either of the NA inhibitor drugs, showed a nine-fold lower sensitivity to
      zanamivir and a 14-fold lower sensitivity to oseltamivir carboxylate compared
      with the mean IC50 of influenza B strains. A decrease in sensitivity to
      oseltamivir carboxylate and RWJ-270201 was also seen in both: a chemiluminescent
      assay and a second different fluorescent assay. Sequence analysis of the
      haemagglutinin HA1 region and the neuraminidase gene of B/Perth/211/2001 revealed
      no amino acid changes in sites that have previously been reported to confer
      resistance to either of the NAI drugs. Further investigations are in progress to
      identify the basis for this reduced sensitivity.

PMID- 15163512
TI  - High level expression of Streptomyces mobaraensis transglutaminase in
      Corynebacterium glutamicum using a chimeric pro-region from Streptomyces
      cinnamoneus transglutaminase.
AB  - We previously observed secretion of native-type Streptomyces mobaraensis
      transglutaminase (MTGase) in Corynebacterium glutamicum by co-expressing the
      subtilisin-like protease SAM-P45 from S. albogriseolus which processes the pro
      region. In the present study, we have used a chimeric pro-region consisting of S.
      mobaraensis and Streptomyces cinnamoneus transglutaminases for the production of
      MTGase in C. glutamicum. As a result, secretion of MTGase using the chimeric pro
      region is increased compared to that using the native pro-region.

PMID- 15163513
TI  - In vivo excision and amplification of large human genomic segments using the
      Cre/loxP-and large T antigen/SV40 ori-mediated machinery.
AB  - In vivo excision and amplification of pre-determined large genomic segments,
      directly from the genome of a natural host, can be a powerful tool for obtaining
      the genomic sequences with minimum rearrangements. In this study, an in vivo
      excision and amplification system in human BJAB cells was devised by combining
      the Cre/loxP system of bacteriophage P1 and the large T antigen/SV40 ori system
      of Simian virus 40. Two loxP sequences, each of which serves as a recognition
      site for recombinase Cre, were integrated unidirectionally into 5'- and 3'
      untranslated regions (UTRs) of the human iNOS. An SV40 ori sequence, which serves
      as a conditional replication system, was inserted between the loxP sites. Trans
      acting genes cre and large T antigen, which were under the control of a
      tetracycline responsive promoter, were also inserted into the 5'- and 3'-UTRs of
      the iNOS, respectively, by homologous recombination. Upon induction by
      doxycycline, the 45-kb iNOS genomic fragment of human chromosome 17 flanked by
      two loxP sites was excised and amplified up to about 45 copies per cell. Our
      method is very useful for obtaining large genomic fragments in quantities
      directly from human cells without using foreign hosts. Therefore, our approach
      can be used effectively for gap sequencing of a genome, gene therapy, and
      functional analysis of unknown genes in human cells.

PMID- 15163514
TI  - Biodegradation of phenanthrene in soil-slurry systems with different mass
      transfer regimes and soil contents.
AB  - The effect of soil contents and mass transfer rates on soil bioremediation was
      investigated. Phenanthrene, a 3-ring polycyclic aromatic hydrocarbon (PAH), was
      chosen as a model target compound. The biodegradation tests were performed in
      soil-slurry systems at two distinct mass transfer rates: fast in flasks tests at
      150 rpm and slow in roller-bottle tests at 2 rpm. The rate of phenanthrene
      biodegradation was similar at low soil content (2 wt.%) in both slurry systems,
      but the rates at high soil contents (6 and 18 wt.%) were higher in the roller
      bottle tests. The maximum utilization rate constant for sorbed-phase
      biodegradation obtained from curve fitting using a mathematical model was
      decreased in the flask tests with increasing soil content, while not decreased in
      the roller-bottle tests.

PMID- 15163515
TI  - The influence of cell and substratum surface hydrophobicities on microbial
      attachment.
AB  - This study investigated the role of hydrophobic/hydrophilic interaction between
      bacterial and support surfaces in microbial adhesion, and a model that correlates
      microbial adhesion and relative cell-hydrophobicity defined as the ratio of cell
      support surface hydrophobicity over cell-support hydrophilicity was derived. This
      model quantitatively describes how cell hydrophobic and hydrophilic interactions
      affect microbial adhesion, and offers deep insights into the thermodynamic
      mechanisms of microbial adhesion. The proposed model was verified by literature
      data. It appears that a high cell-hydrophobicity strongly facilitates microbial
      adhesion on both hydrophobic and hydrophilic support surfaces.

PMID- 15163516
TI  - A novel cell-free protein synthesis system.
AB  - An efficient cell-free protein synthesis system has been developed using a novel
      energy-regenerating source. Using the new energy source, 3-phosphoglycerate (3
      PGA), protein synthesis continues beyond 2 h. In contrast, the reaction rate
      slowed down considerably within 30-45 min using a conventional energy source,
      phosphoenol pyruvate (PEP) under identical reaction conditions. This improvement
      results in the production of twice the amount of protein obtained with PEP as an
      energy source. We have also shown that Gam protein of phage lambda, an inhibitor
      of RecBCD (ExoV), protects linear PCR DNA templates from degradation in vitro.
      Furthermore, addition of purified Gam protein in extracts of Escherichia coli
      BL21 improves protein synthesis from PCR templates to a level comparable to
      plasmid DNA template. Therefore, combination of these improvements should be
      amenable to rapid expression of proteins in a high-throughput manner for
      proteomics and structural genomics applications.

PMID- 15163517
TI  - Effect of acyl donor chain length and substitutions pattern on the enzymatic
      acylation of flavonoids.
AB  - Rutin and esculin were enzymatically acylated with different aliphatic acids as
      acyl donors (fatty acids, dicarboxylic acids and omega-substituted fatty acids)
      by an immobilized lipase from Candida antarctica. The effect of the water content
      and the acyl donors pattern on the flavonoid initial acylation rate and
      conversion yield were investigated. The obtained results indicated that the water
      content of the medium has a strong effect on the performance of these reactions.
      The best conversion yields were reached when the water content was kept lower
      than 200 ppm. At low water content of the medium, these syntheses are influenced
      by carbon chain length and substitution pattern of the acyl donors. Higher
      conversion yields of esculin and rutin (>70%) were obtained with aliphatic acids
      having high carbon chain length (>12). Moreover, it has been found that the amine
      and thiol groups on omega-substituted fatty acid chain were unfavourable to these
      reactions. The 1H NMR and 13C NMR analyses of some synthesized esters (esculin
      and rutin palmitate) show that only monoesters were produced and that the
      esterification takes place on the primary OH of glucose moiety of the esculin and
      on the secondary 4"'-OH of the rhamnose residue of rutin.

PMID- 15163518
TI  - Synthesis of alkylgalactosides using whole cells of Bacillus pseudofirmus species
      as catalysts.
AB  - Whole cells of alkaliphilic Bacillus pseudofirmus AR-199, induced for beta
      galactosidase activity, were used for the synthesis of 1-hexyl-beta-d-galactoside
      and 1-octyl-beta-d-galactoside, respectively, by transglycosylation reaction
      between lactose and the corresponding alcohol acceptor. The product yield was
      strongly influenced by the initial water content in the reaction mixture. Water
      content of 10% (v/v) was optimal providing 3.6-36 mM hexyl galactoside from 10 to
      150 mM lactose, and no secondary product hydrolysis. Product yield could be
      enhanced by supplementing the reaction mixture with more cells or partly
      replacing the product with fresh substrate, but was decreased with time to the
      initial equilibrium level. Cell permeabilisation or disruption resulted in
      increased reaction rate and higher product yield but was followed by product
      hydrolysis. Octyl galactoside synthesis using whole cells was optimal at water
      content of 2% (v/v) with a yield of 26%. The cells were immobilised in cryogels
      of polyvinyl alcohol for use in continuous process, where hexyl galactoside was
      produced with a constant yield of 50% from 50mM lactose for at least a week.

PMID- 15163519
TI  - Continuous ethanol production and evaluation of yeast cell lysis and viability
      loss under very high gravity medium conditions.
AB  - A combined bioreactor system, composed of a stirred tank and a three-stage
      tubular bioreactor in series and with a total working volume of 3260 ml, was
      established. Continuous ethanol production was carried out using Saccharomyces
      cerevisiae and a very high gravity (VHG) medium containing 280 g l(-1) glucose.
      An average ethanol concentration of 124.6 g l(-1) or 15.8% (v) was produced when
      the bioreactor system was operated at a dilution rate of 0.012 h(-1). The yield
      of ethanol to glucose consumed was calculated to be 0.484 or 94.7% of its
      theoretical value of 0.511 when ethanol entrapped in the exhaust gas was
      incorporated. Meanwhile, quasi-steady states and non-steady oscillations were
      observed for residual glucose, ethanol and biomass concentrations for all of
      these bioreactors during their operations. Models that can be used to predict
      yeast cell lysis and viability loss were developed.

PMID- 15163520
TI  - Efficient MILP formulations for the optimal synthesis of chromatographic protein
      purification processes.
AB  - The use of recombinant proteins has increased greatly in recent years, as well as
      the techniques used for their purification. The selection of an efficient process
      to purify proteins is a major bottleneck found when trying to scale up results
      obtained in the laboratory to a large-scale industrial process. One of the main
      challenges in the synthesis of downstream purification stages in biotechnological
      processes is the appropriate selection and sequencing of chromatographic steps.
      The objective of this work is to develop mixed integer linear programming models
      for the synthesis of protein purification processes. Models for each
      chromatographic technique rely on physicochemical data of a protein mixture,
      which contains the desired product and provide information on its potential
      purification. Formulations that are based on convex hull representations are
      proposed to calculate the minimum number of steps from a set of chromatographic
      techniques that must achieve a specified purity level and alternatively to
      maximize purity for a given number of steps. The proposed models are tested in
      several examples with experimental data and present time reductions of up to
      three orders of magnitude when compared to big-M formulations.

PMID- 15163521
TI  - Identification and characterization of a phytase of potential commercial
      interest.
AB  - Phytases catalyse the hydrolytic degradation of phytic acid and its salts and are
      added to monogastric animal feed to ameliorate the negative environmental and
      nutritional consequences of dietary phytate. Screening of 58 microbial strains
      identified a phytase produced by Rhizopus oligosporus ATCC 22959 that displayed
      physicochemical characteristics likely to render it of potential industrial
      interest. The 124 kDa enzyme was purified to homogeneity by anion exchange
      chromatography, gel filtration and chromatofocusing. The monomeric glycosylated
      enzyme (30.5% total carbohydrate) displayed maximum activity at 65 degrees C and
      pH 5.0. It displayed a Km of 10.4 microM, a Vmax of 1.32 nmols(-1) and a Kcat of
      51 s(-1). It is acid tolerant, retaining full activity after incubation at pH 2.0
      for 6h. HPLC analysis indicated the enzyme's ability to almost completely degrade
      phytate. Substrate specificity studies showed its ability to dephosphorylate
      several additional phosphorylated molecules. Activity was unaffected or
      moderately stimulated by a range of metal ions with only Ca2+ exerting a modest
      (13%) inhibitory effect. The enzyme is significantly more thermostable at 80
      degrees C and retains a significantly greater proportion of maximal activity at
      physiological temperatures than do two commercial phytases tested for comparative
      purposes. This may render it of industrial interest.

PMID- 15163522
TI  - Direct detection of 16S rRNA using oligonucleotide microarrays assisted by base
      stacking hybridization and tyramide signal amplification.
AB  - A simple method has been developed and validated for direct, sensitive detection
      and specific identification of 16S rRNA. We first report our direct investigation
      of discrimination efficiency for sequence variations in RNA using oligonucleotide
      microarrays assisted by base stacking hybridization, and demonstrate that the
      sequence variations of double base substitution, single base substitution and
      single base deletion in RNA could be directly identified. With the help of
      tyramide signal amplification (TSA), the detection sensitivity of this method for
      four clinically important bacterial species was below 0.5, 5, 1 and 1 ng of total
      RNA, which are 100-1000 fold more sensitive than the published methods.

PMID- 15163523
TI  - Assessment of DHPLC usefulness in the genotyping of GSTP1 exon 5 SNP: comparison
      to the PCR-RFLP method.
AB  - Single-nucleotide polymorphism (SNP) analysis can be performed by several methods
      such as PCR-RFLP, real time PCR and mass spectrometry. Denaturating High Pressure
      Liquid Chromatography (DHPLC) analysis allows the detection of DNA mutations in
      heteroduplex samples. GSTP1 exon 5 gene presents a single-nucleotide polymorphism
      (a to g) that results into an amino-acid substitution (Ile to Val). Ile and Val
      variants are identified respectively by a and b alleles. This polymorphism
      affects enzyme activity and is highly frequent within Caucasian populations and
      therefore widely studied in the context of SNP related to cancer susceptibility.
      Our goal was to evaluate DHPLC usefulness in detecting a well-known SNP in
      comparison to PCR-RFLP, in the field of molecular epidemiological studies. Fifty
      Caucasian people were genotyped by both methods. Heterozygous samples were
      identified easily at two temperatures using the DHPLC method. Discrimination
      between a/a and b/b homozygous genotypes was done by pooling every homozygous
      sample with a known a/a sample. Our genotyping using both methods resulted in the
      characterisation of 32 (64%) a/a homozygous, 18 (36%) a/b heterozygous and 5
      (10%) b/b homozygous. All samples were also identically genotyped by the two
      methods. Our results show that DHPLC is a good alternative to classical PCR-RFLP
      method in genotyping SNPs. Advantages of this chromatographic method were no
      restriction site needed and a reduced technical time thanks to an automated
      injection. Moreover, unlike classical RFLP gel analysis, DHPLC chromatograms
      provided objective criteria for sample classification.

PMID- 15163524
TI  - Modification of the furanacryloyl-L-phenylalanylglycylglycine assay for
      determination of angiotensin-I-converting enzyme inhibitory activity.
AB  - Angiotensin-I-converting enzyme (ACE, EC 3.4.15.1) plays a central role in the
      regulation of blood pressure in man. The objective of this study was to evaluate
      and modify the furanacryloyl-L-phenylalanylglycylglycine (FAPGG) assay method for
      quantification of ACE activity. The fixed time conditions developed for assay of
      ACE activity were as follows: 0.8 mM FAPGG, 175 + or - 10 units l(-1) ACE,
      incubation at 37 degrees C for 30 min and enzyme inactivation with 100 mM
      ethylenediaminetetra-acetic acid (EDTA). Hydrolysis of FAPGG to FAP and GG was
      quantified by measuring the decrease in absorbance at 340 nm. It was shown that
      increasing the level ACE activity in the assay from 155 to 221 + or - 15 units l(
      1) resulted in a corresponding increase in the apparent IC(50) value for
      Captopril from 9.10 to 39.40 nM. Similar trends in the apparent IC50 values for a
      whey protein hydrolysate were obtained. The results demonstrate the requirement
      for carefully controlling ACE activity levels in the assay in order to obtained
      comparable and reproducible values for the inhibitory potency of ACE inhibitors.

PMID- 15163525
TI  - A rapid method for fibronectin purification on nitrocellulose membranes suitable
      for tissue culture.
AB  - We have developed a simple method for plasma fibronectin purification based on
      the well-known gelatin binding property of fibronectin. In this procedure we
      immobilize the melted gelatin to nitrocellulose membranes; these are then used to
      affinity-purify the fibronectin from the plasma sample. The fibronectin is eluted
      from the membrane by treatment with 8 M urea. The procedure described here gives
      a yield of up to 60% (from presumed fibronectin concentration) and the
      fibronectin obtained is homogeneous in SDS-PAGE and biologically active, as
      assessed by a cell migration assay. The method is rapid, simple, inexpensive,
      does not require the use of chromatographic equipment and is suitable for tissue
      culture applications.

PMID- 15163526
TI  - Real-time turbidimetry of LAMP reaction for quantifying template DNA.
AB  - Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification
      method that allows the synthesis of large amounts of DNA in a short period of
      time with high specificity. As the LAMP reaction progresses, the reaction by
      product pyrophosphate ions bind to magnesium ions and form a white precipitate of
      magnesium pyrophosphate. We designed an apparatus capable of measuring the
      turbidity of multiple samples simultaneously while maintaining constant
      temperature to conduct real-time measurements of the changes in the turbidity of
      LAMP reactions. The time (Tt) required for the turbidity of the LAMP reaction
      solution to exceed a given value was dependent on the quantity of the initial
      template DNA. That is, a graph with the plot of Tt versus the log of the amount
      of initial template DNA was linear from 2 x 10(3) copies (0.01 pg/tube) to 2 x
      10(9) copies (100 ng/tube) of template DNA. These results indicate that real-time
      turbidity measurements of the LAMP reaction permit the quantitative analysis of
      minute amounts of nucleic acids present in a sample, with a high precision over a
      wide range, using a simple apparatus reported in this study.

PMID- 15163527
TI  - Stereoselective RP-HPLC determination of esmolol enantiomers in human plasma
      after pre-column derivatization.
AB  - A stereoselective reversed-phase HPLC assay to determine S-(-) and R-(+)
      enantiomers of esmolol in human plasma was developed. The method involved liquid
      liquid extraction of esmolol from human plasma, using S-(-)-propranolol as the
      internal standard, and employed 2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl
      isothiocyanate as a pre-column chiral derivatization reagent. The derivatized
      products were separated on a 5-microm reversed-phase C18 column with a mixture of
      acetonitrile/0.02 mol/L phosphate buffer (pH 4.5) (55:45, v/v) as mobile phase.
      The detection of esmolol derivatives was made at lambda=224 nm with UV detector.
      The assay was linear from 0.035 to 12 microg/ml for each enantiomer. The
      analytical method afforded average recoveries of 94.8% and 95.5% for S-(-)- and R
      (+)-esmolol, respectively. For each enantiomer, the limit of detection was 0.003
      microg/ml and the limit of quantification for the method was 0.035 microg/ml
      (RSD<14%). The reproducibility of the assay was satisfactory.

PMID- 15163528
TI  - Analysis of solid-phase immobilized antibodies by atomic force microscopy.
AB  - Antibody adsorption to solid surfaces creates a number of constraints that may
      interfere with epitope recognition and ligand-antibody interaction. By optimizing
      the conditions of adsorption, one may minimize these constraints. We have studied
      several factors that affect the antibody adsorption using atomic force microscopy
      (AFM) as a readout mechanism. AFM provides a highly sensitive, label-free method
      for detecting and analyzing molecular interactions. In this report, AFM was used
      to study antibody properties, the efficiency of particle capture and ligand
      antibody interaction using anti-bacteriophage fd antibodies in a solid phase
      assay format. The capture efficiencies of anti-fd preparations adsorbed onto gold
      surfaces under various conditions including pH and antibody concentration were
      determined and compared. The relative sensitivities of each antibody for the
      capture of phage fd as a function of applied phage concentrations was evaluated.
      The collective data indicates that AFM is effective as an analytical instrument
      for studying the functionality of surface adsorbed antibodies in particle capture
      assays. This method of analysis can be extended to rapidly screen and select
      antibodies or other ligands with a specific set of characteristics. As the number
      and complexity of chip-based analytical platforms in proteomics increases, rapid
      selection/screening processes such as that described here will become invaluable.

PMID- 15163529
TI  - Immunoassays and sequence-specific DNA detection on a microchip using enzyme
      amplified electrochemical detection.
AB  - A CMOS fabricated silicon microchip was used as a platform for immunoassays and
      DNA synthesis and hybridization. The chip is covered with a biofriendly matrix
      wherein the chemistries occur. The active silicon chip has over 1000 active
      electrodes that can be individually addressed for both synthesis of DNA and
      protein attachment to a membrane on the chip surface. Additionally, the active
      chip can be further used for the detection of various analytes at the chip
      surface via digital read out resulting from the redox enzymes on the captured
      oligonucleotide or antibody.

PMID- 15163530
TI  - Potassium permanganate as a probe to map DNA-protein interactions in vivo.
AB  - Potassium permanganate (KMnO4) has widely been used in genomic footprinting
      assays to map unusual gene structures, including the melting DNA block in
      transcriptional elongation that results from promoter-proximal pausing of RNA
      polymerase (Pol) II complexes. Although it has been assumed that DNA-bound
      proteins do not protect underlying nucleic acids from KMnO4 modifications, we
      provide evidence herein that this chemical can readily be used to detect nuclear
      factor loading at a promoter when using optimized conditions. Moreover, by
      comparing parallel KMnO4 and dimethylsulfate (DMS) in vivo footprintings, we show
      that the utilization of KMnO4 in combination with another chemical probe
      maximizes the detection of factor occupancy at a DNA regulatory region, thus
      providing a better opportunity to define the actual profiles of DNA-protein
      contacts at given genomic sites in living cells.

PMID- 15163531
TI  - High-throughput non-heme iron assay for animal tissues.
AB  - Iron has been widely studied in nearly every realm of biology. However, current
      methodologies, such as genetic mapping or mutation screening, have been difficult
      to apply due to the lack of robust high-throughput methods for quantifying iron
      levels from cells or tissues. The measurement of total iron levels in tissues,
      usually done with atomic absorption spectroscopy, is impractical for large
      numbers of samples and includes the contribution of heme iron from hemoglobin
      contained in red blood cells. The measurement of non-heme iron by reaction with a
      bathophenanthroline reagent, a commonly used assay reported more than 30 years
      ago, is also not feasible for large-scale analyses because it is cuvette-based.
      We therefore have modified this method to a microplate format that will
      facilitate large-scale analysis. The microplate assay is highly sensitive and
      specific, and is a simple and effective method for the measurement of non-heme
      iron for animal tissues that will enable the application of high-throughput of
      genetic methodologies.

PMID- 15163532
TI  - The human complement factor H: functional roles, genetic variations and disease
      associations.
AB  - Factor H is an essential regulatory protein that plays a critical role in the
      homeostasis of the complement system in plasma and in the protection of bystander
      host cells and tissues from damage by complement activation. Genetic and
      structural data generated during recent years have been instrumental to delineate
      the functional domains responsible for these regulatory activities in factor H,
      which is helping to understand the molecular basis underlying the different
      pathologies associated to factor H. This review summarises our current knowledge
      of the role of factor H in health and disease.

PMID- 15163533
TI  - Genomic and molecular characterization of bovine surfactant protein D (SP-D).
AB  - Collectins are a group of C-type lectins involved in the innate host defense
      against pathogens. They selectively recognize non-self glyco-conjugates on the
      surface of microorganisms and induce lysis, agglutination, and phagocytosis to
      eliminate invading microorganisms. With the perspective of being able to identify
      surfactant protein D (SP-D) polymorphisms associated with immune-compromised
      phenotypes in cattle, we have characterized the gene encoding bovine SP-D and its
      proximal promoter. Cloning and sequencing of the bSP-D gene, including the
      complete 5'-untranslated sequence, reveal that the gene comprises nine exons
      spanning approximately 10.5 kb with an organization resembling the bovine
      conglutinin gene. The gene localizes to the same locus as the conglutinin gene on
      Bos taurus chromosome 28 at position q1.8, which also includes the genes encoding
      CL-43 and CL-46. Several potential cis-regulatory elements, similar to elements
      known to regulate the transcription of human SP-D, were identified in the 5'
      upstream sequence. RT-PCR analysis revealed that bovine SP-D is heavily expressed
      in the lung and the trachea, but also in segments of the gastrointestinal tract,
      the mammary glands and the salivary glands. By genotyping we assigned two
      potential polymorphisms leading to variations in the amino acid composition of
      the carbohydrate recognition domain (242 Glu/Val and 268 Ala/Gly).

PMID- 15163534
TI  - Hydroid TNF-receptor-associated factor (TRAF) and its splice variant: a role in
      development.
AB  - TNF-receptor-associated factors (TRAFs) mediate signaling via tumor necrosis
      factor receptor (TNFR)/TLR molecules, playing a role in cellular processes such
      as growth, differentiation and apoptosis. They have been most studied in the
      immunological context. Within the animal kingdom, TRAFs have been characterized
      from vertebrates, flies and worms. We have cloned and characterized the first
      TRAF homologue from a member of the most basal eumetazoan phylum, the Cnidaria.
      The cnidarian TRAF, HyTRAF1, is a typical member of its family, containing one
      RING finger and five zinc finger domains in its N-terminal region, followed by a
      TRAF domain located at the C terminus. In addition to the full-length mRNA, the
      gene is alternatively spliced to create a shorter isoform, HyTRAF1a, with a
      deletion of 35 amino acids, resulting in a protein with only four zinc fingers.
      This is the first described TRAF alternative splicing in invertebrates. Whereas
      the full-length protein is expressed in most life stages of the animal, the short
      isoform is exclusively found at the larval and early metamorphic stages. This
      stage is characterized by extensive apoptosis, suggesting that HyTRAF1a mediates
      a proapoptotic c-jun N-terminal kinase (JNK) signaling, similar to the murine
      TRAF2A isoform. Based on neighbor joining analysis of TRAF molecules across the
      animal kingdom, we propose that the cnidarian TRAF interacts with TNFR, rather
      than with TLR. Our findings suggest that TNF signaling has evolved in the common
      ancestor to cnidarians and bilaterians and that it has been conserved in the
      entire animal kingdom.

PMID- 15163535
TI  - Protein kinase C beta is dispensable for TCR-signaling.
AB  - PKCbeta has been established to be essential in B cell receptor (BCR) signaling.
      Additionally, a critical role of PKCbeta in TCR/CD28-stimulated regulation of IL
      2 gene transcription but also exocytotic IL-2 secretion was observed in leukemic
      T cell lines. To now study the physiological function of PKCbeta in primary
      CD3(+) T cells, we used our established PKCbeta null mice. Unexpectantly, we did
      not reveal any defect in the development and function of T cells. Proliferative
      responses as well as IL-2 cytokine secretion of PKCbeta-deficient CD3(+) T cells
      induced by allogenic MHC, plate-bound anti-CD3 antibodies (with or without anti
      CD28 costimulation), or mitogenic stimuli such as phorbol ester and Ca(2+)
      ionophore were comparable with wild-type controls. Thus, PKCbeta-deficient T
      cells had similar physiological thresholds for activation in vitro. These
      findings suggest that PKCbeta plays a redundant role in TCR-induced regulation of
      IL-2 cytokine production and T cell proliferation.

PMID- 15163536
TI  - Taenia crassiceps carbohydrates stimulate IL-6 expression in naive murine
      macrophages via Toll-like receptors (TLRs).
AB  - In murine infections of Schistosoma mansoni and Taenia crassiceps, a
      characteristic polarization of the immune response from a Th-1 type to a Th-2
      type occurs with progression of infection. In S. mansoni, egg glycoprotein
      carbohydrates are said to be responsible for this immunomodulatory activity. We
      have previously shown that in vitro systems, T. crassiceps carbohydrates (TCHO)
      up-regulate the expression of interleukin 6 (IL-6) in naive spleen cells, while
      conventional Th-2 cytokines were not detected. In this report, we show that
      peritoneal macrophages are the source of this early IL-6 and that these cells
      recognize T. crassiceps carbohydrates via Toll-like receptors (TLRs). Co
      stimulation experiments with synthetic sugars showed that the most likely active
      moieties in TCHO are Lewis X analogues. To our knowledge, this is the first
      report on native carbohydrates of a helminth parasite stimulating mammalian
      innate immune cells to produce a Th-2 polarizing cytokine (IL-6) via a Toll-like
      receptor. It is hypothesized this is a general mechanism of Th-2 immunodominance
      in helminth infections in mammalian hosts.

PMID- 15163537
TI  - Analysis of lipid rafts in T cells.
AB  - The plasma membrane of T cells is made of a combination of glycosphingolipids and
      protein receptors organized in glycolipoprotein microdomains termed lipid rafts.
      The structural assembly of lipid rafts was investigated by various physical and
      biochemical assays. Depending on the differentiation status of T cells, the lipid
      rafts seclude various protein receptors involved in T cell signaling,
      cytoskeleton reorganization, membrane trafficking, and the entry of infectious
      organisms into the cells. This review article summarizes the most common methods,
      and their limits and advantages for analyzing the composition and assembly of
      lipid rafts with protein receptors into lipid rafts microdomains in plasma
      membrane of T cells. It also includes new methods such as ELISA/Polysorp and flow
      cytometry, and a combined sucrose gradient centrifugation-FPLC-Western blot
      strategy developed in our laboratory to study non-covalent interactions between
      the GM1 glycosphingolipid and protein receptors in plasma membrane of T cells.

PMID- 15163538
TI  - Two monoclonal antibodies to precisely the same epitope of type II collagen
      select non-crossreactive phage clones by phage display: implications for
      autoimmunity and molecular mimicry.
AB  - Two monoclonal antibodies (mAb) CB268 and CII-C1 to type II collagen (CII) react
      with precisely the same conformational epitope constituted by the residues ARGLT
      on the three chains of the CII triple helix. The antibodies share structural
      similarity, with most differences in the complementarity determining region 3 of
      the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by
      screening two nonameric phage-displayed random peptide libraries. For each mAb,
      there were phage clones (phagotopes) that reacted strongly by ELISA only with the
      selecting mAb, and inhibited binding to CII only for that mAb, not the alternate
      mAb. Nonetheless, a synthetic peptide RRLPFGSQM corresponding to an insert from a
      highly reactive CII-C1-selected phagotope, which was unreactive (and non
      inhibitory) with CB268, inhibited the reactivity of CB268 with CII. Most phage
      displayed peptides contained a motif in the first part of the molecule that
      consisted of two basic residues adjacent to at least one hydrophobic residue
      (e.g. RRL or LRR), but the second portion of the peptides differed for the two
      mAbs. We predict that conserved CDR sequences interact with the basic-basic
      hydrophobic motif, whereas non-conserved amino acids in the binding sites
      (especially HCDR3) interact with unique peptide sequences and limit cross
      reactivity. The observation that two mAbs can react identically with a single
      epitope on one antigen (CII), but show no cross-reactivity when tested against a
      second (phagotope) indicates that microorganisms could exhibit mimics capable of
      initiating autoimmunity without this being evident from conventional assays.

PMID- 15163539
TI  - Minor interspecies variations in the sequence of the gp53 TSL-1 antigen of
      Trichinella define species-specific immunodominant epitopes.
AB  - Among the Trichinella TSL-1 antigens, whose antigenicity is generally due mainly
      to tyvelose-containing epitopes, gp53 is unusual in that its antigenicity is due
      mainly to protein epitopes. In the present study we mapped two of these epitopes,
      recognized by monoclonal antibodies (mAbs) that specifically recognize gp53 from
      all encysting Trichinella species (mAb US9), or gp53 from Trichinella spiralis
      alone (mAb US5). Based on previously published sequences of this glycoprotein
      [Mol. Biochem. Parasitol. 72 (1995) 253], in this study, we cloned the full gp53
      cDNA from a new strain, Trichinella britovi (ISS 11; AN: ), and from another T.
      spiralis isolate (ISS 115; AN: ). The gp53 sequence comprised an ORF of 1239bp,
      coding for 412 amino acids, with 61 nucleotide differences (resulting in 38
      residue changes) between the two species. Mapping of US5- and US9-recognized
      epitopes was undertaken through the construction and expression in the pGEX4T
      vector of truncated gp53 peptides, and by the construction of peptides derived
      from the antigenic regions. The epitope recognized by mAb US9 was a linear
      peptide of 8 residues, 33Met- 40Ser, located in the amino-terminal region, while
      the corresponding epitope recognized by mAb US5 was a 47-amino acid sequence
      containing two alpha-helix regions flanked by random coils, 290Thr- 336Lys.
      Molecular modeling of these peptides seems to indicate that recognition of the
      US9 epitope depends on the presence of two available hydroxyl groups provided by
      one methionine and one serine on T. spiralis gp53 (not present on Trichinella
      pseudospiralis gp53). Additionally, the stability of the US5 epitope seems to
      depend on correct folding of the 47-amino acid sequence (only present in T.
      spiralis). The relevance of these findings for understanding the antigenic
      recognition of Trichinella TSL-1 antigens, and for further studies to investigate
      possible function(s) of gp53 in Trichinella, is discussed.

PMID- 15163540
TI  - Identification of the cytoskeletal regulatory protein alpha-adducin as a target
      of T cell receptor signaling.
AB  - Quiescent T lymphocytes reorganize the actin cytoskeleton subsequent to
      interaction with antigen presenting cells bearing the appropriate peptide
      antigen. Although both biochemical and genetic evidence indicate that T cell
      receptor-dependent cytoskeletal reorganization is critical to T cell activation,
      the mechanisms that mediate this process remain poorly defined. In this study,
      the cytoskeletal regulatory protein alpha-adducin was identified as a novel
      target of TCR signaling in primary T lymphocytes through the biochemical
      purification of an unknown 120 kDa protein (p120) defined by a fortuitously cross
      reactive phospho-sensitive antiserum. The epitope identified by this antiserum
      defines a previously unrecognized site of phosphorylation localized to amino
      acids 590-620. Both TCR cross-linking and exposure to phorbol ester resulted in
      the phosphorylation-dependent elimination of this epitope. However, while phorbol
      ester induced rapid phosphorylation of both the phospho-sensitive epitope and the
      functionally defined major protein kinase C site present near the carboxy
      terminus (serine 724) of alpha-adducin, only the phospho-sensitive epitope was
      modified upon activation through the TCR. Moreover, inhibition of actin
      polymerization by cytochalasin D blocked this modification. Of particular
      importance, alpha-adducin was not expressed in T cell lines, was completely down
      regulated in primary T cells within 24h of activation and was reduced in
      quiescent memory T cells. These results suggest a model in which reorganization
      of the unique cytoskeletal network that defines a primary quiescent T lymphocyte
      is mediated in part through the TCR-dependent modification and subsequent down
      regulation of alpha-adducin, thereby resulting in a cytoskeletal architecture
      compatible with T cell effector and memory functions.

PMID- 15163541
TI  - Reduced complement receptor 1 (CR1, CD35) transcription in systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease
      characterized by the production of a broad spectrum of autoantibodies against
      nuclear, cytoplasmic and cell surface antigens and immune complex overload.
      Complement receptor 1 (CR1, CD 35), a transmembrane glycoprotein found on the
      surface of erythrocytes, leukocytes and glomerular podocytes plays a key role in
      the clearance of immune complexes and regulation of complement cascade. A drastic
      decline in the level of cell surface CR1 appears to be an important event in
      pathology of SLE. However, the etiology of lower than normal expression of cell
      surface CR1 in this disease is poorly understood. We studied the level of
      leukocyte CR1 transcription in 30 patients with active SLE and 30 controls by
      reverse transcriptase-polymerase chain reaction (RT-PCR) and related the same
      with the level of CR1 protein expression monitored by Western blotting. For RT
      PCR, ratio of CR1/beta-actin was considered for semiquantitation of the level of
      CR1 transcription. Despite individual variation at the level of transcription,
      70% (21 out of 30) of the patients expressed CR1 transcript at the lowest range
      of 0-15% as compared to the controls wherein only 30% (9 out of 30 individuals)
      demonstrated CR1 transcript in this range. Majority of the controls (70%)
      expressed CR1 transcript at the level above 15%. Mean level of CR1 transcript in
      patients (mean +/- S.D. = 21.09 +/- 14.3) was significantly lower than the
      controls (mean +/- S.D. = 48.91 +/- 26.34) (P < 0.001). The level of CR1
      transcription correlated inversely with circulating immune complexes (CIC) (r =
      0.52, P < 0.01). This may suggest that although erythrocyte CR1 is the chief
      vehicle for CIC clearance, drastic decline in leukocyte CR1 expression may impair
      the phagocyte mediated immune complex clearance and contribute to increased
      complement consumption in SLE. Total leukocyte CR1 protein expression was also
      significantly reduced in patients (P < 0.001) as compared to controls. This
      decline at the protein level gave a very significant positive correlation with
      CR1 transcript (r = 0.67, P < 0.01). A marginal increase in soluble CR1 (sCR1)
      was observed in the plasma (ELISA) of SLE patients compared to the controls but
      was insignificant. This paper for the first time brings evidence to suggest that
      reduced synthesis of CR1 contributes substantially to the low cell surface CR1
      expression in SLE. Our findings also suggest increased proteolytic cleavage of
      leukocyte cell surface CR1 in these patients. However, evidence for the latter is
      indirect.

PMID- 15163543
TI  - The potential biological mechanisms of arsenic-induced diabetes mellitus.
AB  - Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have
      demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and
      require further investigation. This paper reviewed the potential biological
      mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of
      the biochemical properties of arsenic. Arsenate can substitute phosphate in the
      formation of adenosine triphosphate (ATP) and other phosphate intermediates
      involved in glucose metabolism, which could theoretically slow down the normal
      metabolism of glucose, interrupt the production of energy, and interfere with the
      ATP-dependent insulin secretion. However, the concentration of arsenate required
      for such reaction is high and not physiologically relevant, and these effects may
      only happen in acute intoxication and may not be effective in subjects
      chronically exposed to low-dose arsenic. On the other hand, arsenite has high
      affinity for sulfhydryl groups and thus can form covalent bonds with the
      disulfide bridges in the molecules of insulin, insulin receptors, glucose
      transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate
      dehydrogenase and alpha-ketoglutarate dehydrogenase). As a result, the normal
      functions of these molecules can be hampered. However, a direct effect on these
      molecules caused by arsenite at physiologically relevant concentrations seems
      unlikely. Recent evidence has shown that treatment of arsenite at lower and
      physiologically relevant concentrations can stimulate glucose transport, in
      contrary to an inhibitory effect exerted by phenylarsine oxide (PAO) or by higher
      doses of arsenite. Induction of oxidative stress and interferences in signal
      transduction or gene expression by arsenic or by its methylated metabolites are
      the most possible causes to arsenic-induced diabetes mellitus through mechanisms
      of induction of insulin resistance and beta cell dysfunction. Recent studies have
      shown that, in subjects with chronic arsenic exposure, oxidative stress is
      increased and the expression of tumor necrosis factor alpha (TNFalpha) and
      interleukin-6 (IL-6) is upregulated. Both of these two cytokines have been well
      known for their effect on the induction of insulin resistance. Arsenite at
      physiologically relevant concentration also shows inhibitory effect on the
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma), a
      nuclear hormone receptor important for activating insulin action. Oxidative
      stress has been suggested as a major pathogenic link to both insulin resistance
      and beta cell dysfunction through mechanisms involving activation of nuclear
      factor-kappaB (NF-kappaB), which is also activated by low levels of arsenic.
      Although without supportive data, superoxide production induced by arsenic
      exposure can theoretically impair insulin secretion by interaction with
      uncoupling protein 2 (UCP2), and oxidative stress can also cause amyloid
      formation in the pancreas, which could progressively destroy the insulin
      secreting beta cells. Individual susceptibility with respect to genetics,
      nutritional status, health status, detoxification capability, interactions with
      other trace elements, and the existence of other well-recognized risk factors of
      diabetes mellitus can influence the toxicity of arsenic on organs involved in
      glucose metabolism and determine the progression of insulin resistance and
      impaired insulin secretion to a status of persistent hyperglycemia or diabetes
      mellitus. In conclusions, insulin resistance and beta cell dysfunction can be
      induced by chronic arsenic exposure. These defects may be responsible for arsenic
      induced diabetes mellitus, but investigations are required to test this
      hypothesis.

PMID- 15163542
TI  - An IgM class anti-neutrophil cytoplasm antibody inhibits neutrophil adhesion and
      apoptosis via a Syk dependent signaling cascade.
AB  - Anti-neutrophil cytoplasm antibodies (ANCA) with specificity for myeloperoxidase
      (MPO) are implicated as pathogenic agents in pauci-immune systemic vasculitis. In
      agreement with previously published observations we show that human neutrophils
      incubated with an MPO-specific IgG class monoclonal antibody are pro-adhesive and
      undergo apoptosis more readily in vitro. If apoptotic neutrophils are incubated
      with this antibody they are readily phagocytosed by macrophages and we show that
      'blocking' antibodies to FcgammaRIIa (CD32) on the macrophage inhibit this
      process. We also examined the effect of E3MPO, a monoclonal anti-MPO antibody
      derived from a patient with severe systemic vasculitis. E3MPO is closely related
      to the cold-agglutinins and bears an epitope recognized by the monoclonal
      antibody 9G4 which is expressed on antibodies derived from the V4-34 germ-line
      immunoglobulin gene. In previous studies, we have shown that anti-MPO antibodies
      present in sera from patients with vasculitis often bear this epitope. In
      contrast to the IgG-class antibody, incubation of neutrophils with E3MPO
      inhibited neutrophil adhesion and apoptosis. Apoptotic neutrophils however were
      phagocytosed more readily by macrophages in the presence of E3MPO. The effects of
      E3MPO on neutrophil adhesion and apoptosis were inhibited by piceatannol, an
      inhibitor of Syk-family kinases; activation of which is associated with cross
      linking of the beta(2)-integrins. We show that surface-expressed MPO co-localizes
      with these beta(2)-integrins and suggest that cross-linking of beta(2)-integrin
      bound MPO by polyvalent antibodies could result in signaling through these
      receptors. We have demonstrated that there are different consequences of Fcgamma
      receptor-dependent and -independent signaling mediated by ANCA.

PMID- 15163544
TI  - Structurally related antitumor effects of flavanones in vitro and in vivo:
      involvement of caspase 3 activation, p21 gene expression, and reactive oxygen
      species production.
AB  - Flavonoids exist extensively in plants and Chinese herbs, and several biological
      effects of flavonoids have been demonstrated. The antitumor effects in colorectal
      carcinoma cells (HT29, COLO205, and COLO320HSR) of eight flavanones including
      flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone, 7-OH flavanone,
      naringenin, nargin, and taxifolin were investigated. Results of the MTT assay
      indicate that 2'-OH flavanone showed the most potent cytotoxic effect on these
      three cells, and cell death induced by 2'-OH flavanone was via the occurrence of
      DNA ladders, apoptotic bodies, and hypodiploid cells, all characteristics of
      apoptosis. Induction of caspase 3 protein processing and enzyme activity
      associated with cleavage of poly(ADP-ribose) polymerase (PARP) was identified in
      2'-OH flavanone-treated cells, and a peptidyl inhibitor (Ac-DEVD-FMK) of caspase
      3 attenuated the cytotoxicity of 2'-OH flavanone in COLO205 and HT-29 cells.
      Elevation of p21 (but not p53) and a decrease in Mcl-1 protein were found in 2'
      OH flavanone-treated COLO205 and HT-29 cells. Elevation of intracellular reactive
      oxygen species (ROS) was detected in 2'-OH flavanone-treated cells by the 2',7'
      dichlorodihydrofluorescein diacetate (DCHF-DA) assay, and ROS scavengers
      including 4,5-dihydro-1,3-benzene disulfonic acid (tiron), catalase, superoxide
      dismutase (SOD), and pyrrolidine dithiocarbamate (PDTC) suppressed the 2'-OH
      flavanone-induced cytotoxic effect. Subcutaneous injection of COLO205 induced
      tumor formation in nude mice, and 2'-OH flavanone showed a significant inhibitory
      effect on tumor formation. The appearance of apoptotic cells with H&E staining,
      and an increase in p21, but not p53, protein by immunohistochemistry were
      observed in tumor tissues under 2'-OH flavanone treatment. Primary tumor cells
      (COLO205-X) derived from a tumor specimen elicited by COLO205 were established,
      and 2'-OH flavanone showed an significant apoptotic effect in COLO205-X cells in
      accordance with the appearance of DNA ladders, caspase 3 protein processing, PARP
      protein cleavage, and increasing p21 protein. These results revealed in vitro, ex
      vivo, and in vivo antitumor activities of 2'-OH flavanone via apoptosis
      induction, and indicates that 2'-OH flavanone is an active compound worthy of
      development for cancer chemotherapy.

PMID- 15163545
TI  - Signal transduction of p53-independent apoptotic pathway induced by hexavalent
      chromium in U937 cells.
AB  - It has been reported that the hexavalent chromium compound (Cr(VI)) can induce
      both p53-dependent and p53-independent apoptosis. While a considerable amount of
      information is available on the p53-dependent pathway, only little is known about
      the p53-independent pathway. To elucidate the p53-independent mechanism, the
      roles of the Ca(2+)-calpain- and mitochondria-caspase-dependent pathways in
      apoptosis induced by Cr(VI) were investigated. When human lymphoma U937 cells,
      p53 mutated cells, were treated with 20 microM Cr(VI) for 24 h, nuclear
      morphological changes and DNA fragmentation were observed. Production of hydroxyl
      radicals revealed by electron paramagnetic resonance (EPR)-spin trapping, and
      increase of intracellular calcium ion concentration monitored by digital imaging
      were also observed in Cr(VI)-treated cells. An intracellular Ca(2+) chelator,
      BAPTA-AM, and calpain inhibitors suppressed the Cr(VI)-induced DNA fragmentation.
      The number of cells showing low mitochondrial membrane potential (MMP), high
      level of superoxide anion radicals (O(2)(-)), and high activity of caspase-3,
      which are indicators of mitochondria-caspase-dependent pathway, increased
      significantly in Cr(VI)-treated cells. An antioxidant, N-acetyl-l-cysteine (NAC),
      decreased DNA fragmentation and inhibited the changes in MMP, O(2)(-) formation,
      and activation of caspase-3 induced by Cr(VI). No increase of the expressions of
      Fas and phosphorylated JNK was observed after Cr(VI) treatment. Cell cycle
      analysis revealed that the fraction of G2/M phase tended to increase after 24 h
      of treatment, suggesting that Cr(VI)-induced apoptosis is related to the G2
      block. These results indicate that Ca(2+)-calpain- and mitochondria-caspase
      dependent pathways play significant roles in the Cr(VI)-induced apoptosis via the
      G2 block, which are independent of JNK and Fas activation. The inhibition of
      apoptosis and all its signal transductions by NAC suggests that intracellular
      reactive oxygen species (ROS) are important for both pathways in Cr(VI)-induced
      apoptosis of U937 cell.

PMID- 15163546
TI  - Toxic effects of bis(thiosemicarbazone) compounds and its palladium(II) complexes
      on herpes simplex virus growth.
AB  - Here, we present data on the activity of benzyl bis(thiosemicarbazone); 3,5
      diacyl-1,2,4-triazole bis(4-methylthiosemicarbazone) and their Pd(II) complexes
      against the replication of wild type and of acyclovir (ACV)-resistant, herpes
      simplex virus type 1 (HSV 1) and type 2 (HSV 2) strains. The data were compared
      to those under the action of acyclovir. The testing of cytotoxic activity
      suggests that these compounds may be endowed with important antiviral properties.
      It is interesting to note that the Pd(II)-benzyl bis(thiosemicarbazone) complex,
      2, exhibits a significant activity against acyclovir-resistant viruses R-100 (HSV
      1) and PU (HSV 2) with an in vitro selectivity index (SI) of 8.0 vs. 0.01 for
      acyclovir. This complex also negatively influenced the expression of key
      structural HSV 1 proteins (VP23, gH and gG/gD), thus suppressing simultaneously
      virus entry, transactivation of virus genome, capsid assembly, and cell-to-cell
      spread of infectious HSV progeny.

PMID- 15163547
TI  - Old age and gender influence the pharmacokinetics of inhaled manganese sulfate
      and manganese phosphate in rats.
AB  - In this study, we examined whether gender or age influences the pharmacokinetics
      of manganese sulfate (MnSO(4)) or manganese phosphate (as the mineral form
      hureaulite). Young male and female rats and aged male rats (16 months old) were
      exposed 6 h day(-1) for 5 days week(-1) to air, MnSO(4) (at 0.01, 0.1, or 0.5 mg
      Mn m(-3)), or hureaulite (0.1 mg Mn m(-3)). Tissue manganese concentrations were
      determined in all groups at the end of the 90-day exposure and 45 days later.
      Tissue manganese concentrations were also determined in young male rats following
      32 exposure days and 91 days after the 90-day exposure. Intravenous (54)Mn tracer
      studies were also performed in all groups immediately after the 90-day inhalation
      to assess whole-body manganese clearance rates. Gender and age did not affect
      manganese delivery to the striatum, a known target site for neurotoxicity in
      humans, but did influence manganese concentrations in other tissues. End-of
      exposure olfactory bulb, lung, and blood manganese concentrations were higher in
      young male rats than in female or aged male rats and may reflect a portal-of
      entry effect. Old male rats had higher testis but lower pancreas manganese
      concentrations when compared with young males. Young male and female rats exposed
      to MnSO(4) at 0.5 mg Mn m(-3) had increased (54)Mn clearance rates when compared
      with air-exposed controls, while senescent males did not develop higher (54)Mn
      clearance rates. Data from this study should prove useful in developing dosimetry
      models for manganese that consider age or gender as potential sensitivity
      factors.

PMID- 15163548
TI  - Hormesis: from marginalization to mainstream: a case for hormesis as the default
      dose-response model in risk assessment.
AB  - The paper provides an account of how the hormetic dose response has emerged in
      recent years as a serious dose-response model in toxicology and risk assessment
      after decades of extreme marginalization. In addition to providing the
      toxicological basis of this dose-response revival, the paper reexamines the
      concept of a default dose model in toxicology and risk assessment and makes the
      argument that the hormetic model satisfies criteria (e.g., generalizability,
      frequency, application to risk assessment endpoints, false positive/negative
      potential, requirements for hazard assessment, reliability of estimating risks,
      capacity for validation of risk estimates, public health implications of risk
      estimates) for such a default model better than its chief competitors, the
      threshold and linear at low dose models. The selection of the hormetic model as
      the default model in risk assessment for noncarcinogens and specifically for
      carcinogens would have a profound impact on the practice of risk assessment and
      its societal implications.

PMID- 15163549
TI  - Apoptotic injury in cultured human hepatocytes induced by HMG-CoA reductase
      inhibitors.
AB  - Hepatotoxicity is the major complaint during therapy with lipid-lowering agents
      such as statins, although the cellular mechanisms underlying the statin-induced
      liver injury are not fully understood. Using cultured human hepatocytes, we
      investigated the effects of lipophilic as well as hydrophilic statins on the cell
      viability. Lipophilic statins, including simvastatin, lovastatin, cerivastatin,
      fluvastatin and atorvastatin, reduced the viability of hepatocytes as assessed by
      the mitochondrial enzyme activity to reduce WST-8, however, a hydrophilic
      pravastatin did not cause cell injury. The simvastatin-induced loss of cell
      viability was attenuated by mevalonate or geranylgeranyl pyrophosphate.
      Simvastatin-induced DNA fragmentation and increased the number of cells stained
      with annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling, both of which were reversed by caspase inhibitors such as zDEVD-fmk,
      zLEHD-fmk and zIETD-fmk. Consistent with these data, the activities of caspase-3,
      caspase-9 and caspase-8 were elevated by simvastatin. Simvastatin reduced the
      protein content and mRNA expression for bcl-2 without affecting bax mRNA
      expression. On the other hand, both lipophilic and hydrophilic statins
      significantly reduced the content of endogenous cholesterol. These findings
      suggest that lipophilic statins cause an apoptotic injury in human hepatocytes by
      stimulating caspase-3 subsequent to the activation of caspase-9 and caspase-8, in
      which the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase may be
      involved.

PMID- 15163550
TI  - The cystic fibrosis mutation G1349D within the signature motif LSHGH of NBD2
      abolishes the activation of CFTR chloride channels by genistein.
AB  - Cystic fibrosis (CF) is a common lethal genetic disease caused by autosomal
      recessive mutations of the cystic fibrosis transmembrane conductance regulator
      (CFTR) chloride channel that belongs to the ATP-Binding Cassette (ABC) family of
      transporters. The class III CF mutations G551D and G1349D are located within the
      "signature" sequence LSGGQ and LSHGH of NBD1 and NBD2, respectively. We have
      constructed by site-directed mutagenesis vectors encoding green fluorescent
      protein (GFP)-tagged wild-type (wt) CFTR or CFTR containing delF508, G551D,
      G1349D and G551D/G1349D to study their pharmacology after transient expression in
      COS-7 cells. We show that IBMX and the benzo[c]quinolizinium derivative MPB-91
      stimulates the activity of G1349D-, G551D- and G551D/G1349D-CFTR only in the
      presence of cAMP-promoting agents like forskolin or cpt-cAMP. Similar half
      maximal effective concentrations (EC(50)) of MPB-91 (22-36microM) have been
      determined for wt-, G551D-, G1349D- and G551D/G1349D-CFTR. The isoflavone
      genistein stimulates wild-type (wt)- and delF508-CFTR channel activity in a non
      Michaelis-Menten manner. By contrast, the response of G1349D- and G551D-CFTR to
      genistein is dramatically altered. First, genistein is not able to stimulate
      G1349D- and G551D/G1349D-CFTR. Second, genistein stimulates G551D-CFTR without
      any inhibition at high concentration. We conclude from these results that whereas
      G551 in NBD1 is an important molecular site for inhibition of CFTR by genistein,
      the symmetrical G1349 in NBD2 is also one major site but for the activation of
      CFTR by genistein. Because both mutations alter specifically the mechanism of
      CFTR channel activation by genistein, we believe that the signature sequences of
      CFTR act as molecular switches that upon interaction with genistein turn on and
      off the channel.

PMID- 15163551
TI  - NO-donating nonsteroidal antiinflammatory drugs (NSAIDs) inhibit colon cancer
      cell growth more potently than traditional NSAIDs: a general pharmacological
      property?
AB  - The novel nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs),
      consisting of a traditional NSAID to which a NO releasing moiety is covalently
      attached, may have an important role in colon cancer prevention and/or treatment.
      Preclinical studies have shown that NO-aspirin (NO-ASA) is more potent than
      traditional ASA in preventing colon cancer. Preclinical and clinical studies have
      also documented its superior safety, compared to traditional ASA. To evaluate the
      role of this structural modification on the cancer cell growth inhibitory effect
      of NSAIDs, we studied seven pairs of traditional NSAIDs (ASA, salicylic acid,
      indomethacin, sulindac, ibuprofen, flurbiprofen, piroxicam) and their
      corresponding NO-NSAIDs. All NO-NSAIDs (except NO-piroxicam which is a salt and
      not a true NO-NSAID) have greater potency in inhibiting HT-29 and HCT-15 colon
      cancer cell growth compared to their NSAID counterparts: the IC(50)s of the NO
      NSAIDs were enhanced between 7- and 689-fold in HT-29 cells and 1.7- to 1083-fold
      in HCT-15 cells over those of the corresponding NSAIDs. Their growth inhibitory
      effect is due to a profound cell kinetic effect consisting of reduced cell
      proliferation and enhanced cell death. Since HT-29 cells express cyclooxygenases
      but HCT-15 do not, this effect appears independent of cyclooxygenase in the colon
      cancer cells. Thus the structural modification of these traditional NSAIDs
      leading to NO-NSAIDs enhances their potency in inhibiting colon cancer cell
      growth. Our findings suggest that the enhanced potency imparted on NSAIDs by this
      structural modification represents a pharmacological property that may be a
      general one for this class of compounds.

PMID- 15163552
TI  - Polyhydroxylated 2-styrylchromones as potent antioxidants.
AB  - Four polyhydroxylated 2-styrylchromones, structurally related to flavones and
      cinnamic acid, have been studied. An SC derivative with OH groups only at
      positions 3' and 4' on the styryl moiety and another SC bearing an additional OH
      group at position 5 on the benzopyrone ring were more potent inhibitors of the
      Cu2+-induced peroxidation of LDL than the flavonoid quercetin. Fluorescence and
      absorption spectroscopies suggested that one LDL particle may bind 40 SC
      molecules. A pulse radiolysis study in pH 7 buffered micellar solutions of
      neutral TX100 and positively charged CTAB demonstrated that one-electron
      oxidation by *Br2-, *O2- and tryptophan radicals (8Trp) depends strongly on the
      micellar microenvironment. All SCs were readily oxidized by *O2- in CTAB micelles
      (rate constants: 6-18 x 10(6) M(-1) s(-1)). In TX100 micelles only the SC
      derivative with OH groups in position 3' and 4' reacted with *O2- (rate constant:
      1.1 x 10(6) M(-1)s(-1)). In CTAB, electron transfer to *Trp radicals was observed
      for all SCs with rate constants > or =3.2 x 10(7) M(-1) s(-1). In TX100 micelles,
      this reaction occurred solely with the derivative bearing OH groups only at
      positions 3' and 4'.

PMID- 15163553
TI  - Intrinsic activity and comparative molecular dynamics of buspirone analogues at
      the 5-HT(1A) receptors.
AB  - In CNS, the 5-hydroxytryptamine(1A) (5-HT(1A)) receptors exist in two different
      populations with different behavioural and physiological effects: (1)
      somatodendritic autoreceptors located pre-synaptically of 5-HT containing neurons
      and (2) receptors located post-synaptic to 5-HT containing neurons. Clinical
      studies have shown that 5-HT(1A) partial agonists have anxiolytic properties,
      while antagonists of pre-synaptical autoreceptors shorten the onset time of
      selective serotonin reuptake inhibitors (SSRIs). In the present study, the pre-
      and post-synaptic activity of structural analogues of buspirone was evaluated in
      animal models. A three dimensional model of the 5-HT(1A) receptor was used to
      study their interaction modes and helical displacements upon receptor binding.
      The predicted receptor-ligand interactions indicated similarities in the receptor
      binding modes for all buspirone analogues, and no clear relationship between
      receptor contact residues and activity at pre- and post-synaptic receptors.
      Comparative molecular dynamics (MD) simulations for 650ps indicated that pre
      synaptic antagonistic behaviour is connected to large displacements of
      transmembrane helix (TMH) 7 upon binding, while pre-synaptic agonistic behaviour
      is connected to large displacements of TMH2 and small displacements of TMH7. Post
      synaptic partial agonist behaviour is connected to large displacements of TMH4
      and TMH5 upon binding, while post-synaptic antagonists only slightly displace
      these helices.

PMID- 15163554
TI  - Functional characterization of genetic polymorphisms identified in the human
      cytochrome P450 4F12 (CYP4F12) promoter region.
AB  - The human cytochrome CYP4F12 has been shown to be active toward inflammatory
      mediators and exogenous compounds such as antihistaminic drugs. In the present
      study, we report the first investigation of polymorphisms in the human CYP4F12
      gene. A screening for sequence variations in the 5'-flanking region was performed
      by a Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR
      SSCP) strategy, using DNA samples from 53 unrelated French individuals of
      Caucasian origin. Several polymorphisms were identified, comprising a large
      deletion located in intron 1 (CYP4F12*v1), two isolated substitutions -402G>A
      (CYP4F12*v3) and -188 T>C (CYP4F12*v4) and nine combined mutations, -474T>C, 
      279A>C, -224A>G, -173G>A, -145C>G, -140T>C, -126T>C, -56T>C, and -21T>G
      (CYP4F12*v2). Considering the nature and location of the polymorphisms
      characterizing the CYP4F12*v1 and *v2, the functional relevance of those two
      allelic variants was further examined by transfecting different cell lines with
      constructs of the related region of the CYP4F12/luciferase reporter gene. Both
      alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell
      line and, therefore, are likely to determine interindividual differences in
      CYP4F12 gene expression.

PMID- 15163555
TI  - Induction of cyclooxygenase-2 by bovine type I collagen in macrophages via C/EBP
      and CREB activation by multiple cell signaling pathways.
AB  - Bovine type I collagen (Col-I) is utilized for medical purposes such as cosmetic
      surgery and wrinkle removal. Cyclooxygenase-2 (COX-2) plays roles in
      pathophysiological processes including inflammation and tumorigenesis. This study
      examines the effects of Col-I on the COX-2 expression and the signaling pathways
      in macrophages. Col-I increased the levels of COX-2 protein and mRNA in serum
      stimulated Raw264.7 cells in a time- and concentration-dependent manner.
      Treatment of cells with Col-I increased CCAAT/enhancer binding protein (C/EBP)
      DNA binding. Antibody supershift experiments revealed that C/EBP DNA binding
      activity induced by Col-I depended largely on C/EBPbeta and C/EBPdelta.
      Immunocytochemistry showed that Col-I induced nuclear translocation of C/EBPbeta
      and C/EBPdelta, whose activation contributes to COX-2 induction. Overexpression
      of the dominant-negative mutant form of C/EBP abolished COX-2 induction by Col-I.
      Col-I also increased cyclic-AMP response element binding protein (CREB) binding
      to DNA. Inhibition of focal adhesion kinase (FAK) or downstream phosphoinositide
      3-kinase and p70S6 kinase by specific chemical inhibitors prevented COX-2
      induction by Col-I, and C/EBP and CREB from binding to their consensus DNA
      oligonucleotides. Experiments using chemical inhibitors or dominant-negative
      mutant vectors showed that the mitogen-activated protein (MAP) kinase pathways
      including p38-kinase and extracellular signal-regulated kinase (ERK1/2), but not
      c-Jun N-terminal kinase (JNK1), simultaneously regulated COX-2 induction by Col
      I. This was in agreement with inhibition of Col-I-inducible C/EBP and CREB DNA
      binding by concomitant treatment with SB203580 and PD98059. These results provide
      evidence that Col-I induces COX-2 in serum-stimulated macrophages and that the
      multiple cell signaling pathways involving Src-focal adhesion kinase,
      phosphoinositide 3-kinase, and MAP kinases regulate COX-2 induction by Col-I via
      C/EBP and CREB activation.

PMID- 15163556
TI  - Prevention of macrophage adhesion molecule-1 (Mac-1)-dependent neutrophil firm
      adhesion by taxifolin through impairment of protein kinase-dependent NADPH
      oxidase activation and antagonism of G protein-mediated calcium influx.
AB  - Taxifolin has been reported to down-regulate the expression of intercellular
      adhesion molecule-1 (ICAM-1), a receptor-mediating firm adhesion with beta2
      integrin (e.g., Mac-1) expressed on leukocytes. To evaluate whether taxifolin
      could modulate Mac-1-dependent firm adhesion by neutrophils, and the possible
      mechanism(s) underlying its anti-inflammatory action, its effects on N-formyl
      methionyl-leucyl-phenylalanine (fMLP) or phorbol-12-myristate-13-acetate (PMA)
      activated peripheral human neutrophils were studied. Pretreatment with taxifolin
      (1-100 microM) concentration-dependently diminished fMLP- or (PMA)-induced Mac-1
      dependent firm adhesion and upexpression of surface Mac-1. Mobilisation of
      intracellular calcium and production of reactive oxygen species (ROS) signal the
      upexpression of Mac-1 and firm adhesion by neutrophils. Taxifolin impeded the
      calcium influx induced by fMLP (a receptor-mediated activator) or AlF(4)(-) (a G
      protein-mediated activator). Taxifolin also effectively inhibited the fMLP- or
      PMA-induced ROS production with 50% inhibitory concentration (IC(50)) less than
      10microM, possibly through impairing the activation of NADPH oxidase, a major ROS
      generating enzyme in neutrophils, by restricting the activation of p38 mitogen
      activated protein kinase (p38 MAPK) and protein kinase C (PKC). In conclusion, we
      propose that impairment of ROS production by NADPH oxidase through interfering
      with p38 MAPK- and/or PKC-dependent signals, and antagonism of G protein-mediated
      calcium influx may account for the inhibition of Mac-1-dependent neutrophil firm
      adhesion that confers taxifolin the anti-inflammatory activity.

PMID- 15163557
TI  - Counteracting effects of NADPH oxidase and the Na+/Ca2+ exchanger on membrane
      repolarisation and store-operated uptake of Ca2+ by chemoattractant-activated
      human neutrophils.
AB  - This study was designed to investigate the possible involvement of NADPH oxidase
      and the Na(+)/Ca(2+) exchanger in regulating membrane repolarisation and store
      operated uptake of Ca(2+) by FMLP (1 microM)-activated human neutrophils.
      Diphenyleneiodonium chloride (DPI, 5-10 microM) and KB-R7943 (2.5-10 microM),
      inhibitors of NADPH oxidase and the reverse mode of the Na(+)/Ca(2+) exchanger
      respectively, were used as pharmacological probes. Transmembrane fluxes of
      Ca(2+), K(+) and Na(+) were determined radiometrically, while alterations in
      membrane potential and cytosolic Ca(2+) were evaluated using spectrofluorimetric
      procedures. DPI, added to the cells at the time of maximum FMLP-activated
      membrane depolarisation, accelerated the rates of both membrane repolarisation
      and influx of Ca(2+), while KB-R7943 effectively antagonised these processes. SKF
      96365 (10 microM), an antagonist of store-operated Ca(2+) channels, abolished the
      influx of Ca(2+) into FMLP-activated neutrophils, but had no effects on membrane
      repolarisation, suggesting that the Na(+)/Ca(2+) exchanger is primarily involved
      in mediating membrane repolarisation, thereby facilitating uptake of Ca(2+) via
      store-operated channels. These observations are compatible with prominent
      negative and positive regulatory roles for NADPH oxidase and the Na(+)/Ca(2+)
      exchanger respectively in regulating the rates of membrane repolarisation and
      store-operated uptake of Ca(2+) by chemoattractant-activated neutrophils.

PMID- 15163558
TI  - Reduced basal nitric oxide bioavailability and platelet activation in young
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the role of basal nitric oxide (NO) bioavailability for
      platelet activation in young spontaneously hypertensive rats before onset of
      hypertension. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP)
      in platelets was used as a sensitive monitor of in vivo NO bioavailability.
      METHODS AND RESULTS: Whole blood samples were taken from 10-week-old Wistar-Kyoto
      rats (WKY) and spontaneously hypertensive rats (SHR). In vivo surface-expression
      of P-selectin and platelet-binding of fibrinogen were assessed by flow cytometry.
      Platelet VASP-phosphorylation at its serine 239 (Ser239) and serine 157 (Ser157)
      residues was assessed using specific antibodies to determine NO bioavailability
      in vivo, and compared with endothelial vasomotor function. The increment in
      vascular tone following inhibition of NO-synthase in slightly preconstricted
      aortic rings was reduced indicating less NO formation under physiological
      stimulation (WKY 71.1+/-4.1%; SHR 57.8+/-2.4%, P<0.05). In vivo platelet VASP
      phosphorylation was significantly reduced at both phosphorylation sites in SHR
      (mean fluorescence for Ser239: WKY: 15.2+/-0.6; SHR: 11.7+/-0.5, P<0.01; Ser157:
      WKY: 53.0+/-3.0; SHR: 35.0+/-3.5, P<0.05). Surface-expression of P-selectin and
      membrane-bound fibrinogen were significantly enhanced in SHR compared with WKY (P
      selectin: WKY: 23.2+/-3.4; SHR 58.3+/-7.9, P<0.001; platelet-bound fibrinogen:
      WKY: 8.6+/-0.5; SHR: 13.5+/-1.1, P<0.001). In vitro preincubation of platelets
      with the NO donor sodium nitroprusside normalized platelet surface-expression of
      P-selectin in SHR. CONCLUSION: Using VASP-phosphorylation as a sensitive monitor
      of in vivo NO bioavailability, these data provide evidence that reduced vascular
      NO formation in vivo contributes to increased platelet activation in young SHR.

PMID- 15163559
TI  - Up-regulation of low-density lipoprotein receptor in human hepatocytes is induced
      by sequestration of free cholesterol in the endosomal/lysosomal compartment.
AB  - Up-regulation of low-density lipoprotein receptor (LDLr) is a key mechanism to
      control elevated plasma LDL-cholesterol levels. In the present paper, we compare
      the ability of four distinct pharmacological drugs to up-regulate LDLr expression
      in human hepatocytes. HepG2 cells were treated with the steroidal analog GW707,
      the oxidosqualene cyclase inhibitor U18666A, the 3beta-hydroxysterol Delta(7)
      reductase inhibitor AY-9944 and the vacuolar-type ATPase inhibitor bafilomycin
      A1. We found that the four compounds induced sequestration of free cholesterol in
      the endosomal/lysosomal compartment leading to a positive filipin staining
      pattern and a complete inhibition of cholesteryl ester synthesis. As a
      consequence of the sequestration of cholesterol, the expression and the activity
      of LDLr were strongly induced resulting from a transcriptional effect which was
      measured by a reporter gene assay. These effects were fully abolished when an
      exogenous water soluble cholesterol analog was added to the cells. These findings
      have led to the identification of a common mechanism to up-regulate LDLr
      expression in human hepatocytes and may represent an interesting alternative
      approach to identify new hypolipidemic drugs.

PMID- 15163560
TI  - Chronic ethanol ingestion by mice increases expression of CD80 and CD86 by
      activated macrophages.
AB  - Results from previous studies from our laboratory have shown that T cells
      obtained from the spleens of C57BL/6 mice that consumed ethanol chronically have
      increased expression of activation markers and increased second signal
      independent production of interferon-gamma (IFN-gamma). We now report that in
      vitro-activated CD11b(+) splenocytes obtained from C57BL/6 and BALB/c mice that
      consumed ethanol chronically express increased levels of the T cell co
      stimulatory molecules CD80 and CD86. CD11b(+) splenocytes encompass at least two
      populations: the CD11b(+)Gr.1(-) population, which is primarily monocytes
      macrophages, and a smaller CD11b(+)Gr.1(+) population, which is in the myelocytic
      monocytic cell series and contains precursors of both macrophages and
      neutrophils. Evaluation of cultures of purified CD11b(+) cells, obtained from
      mice that consumed ethanol chronically, incubated overnight, showed increased up
      regulation of CD80 and CD86 expression on Gr.1(-) mouse splenic macrophages.
      Results of functional studies of purified CD11b(+) cells have demonstrated that
      CD11b(+) cells obtained from C57BL/6 mice that were exposed to ethanol
      chronically secrete higher levels, in comparison with the levels secreted by
      CD11b(+) cells obtained from control animals, of nitric oxide and several
      proinflammatory cytokines after stimulation by the oligodeoxynucleotide (ODN) CpG
      1826. These findings indicate that CD11b(+) splenocytes are in some way
      sensitized to activating stimuli by chronic ethanol exposure in vivo. Such cells
      may contribute to systemic immunodysregulation, including T-cell activation, by
      providing abnormal second signals to T cells, or through excessive release of
      cytokines, such as interleukin (IL)-6 or IL-12.

PMID- 15163562
TI  - Microarray gene analysis of the liver in a rat model of chronic, voluntary
      alcohol intake.
AB  - The mechanisms underlying alcoholic liver disease are not fully understood. It
      has been established that alcohol interferes with transcriptional and
      translational regulatory steps of cell function. To understand such an effect,
      assessment of alcohol-induced changes in the simultaneous expression of a large
      number of genes may prove very useful. The purpose of the current study was to
      test a large number of genes ( approximately 8700) for possible changes in
      expression induced by alcohol alone or in addition to treatment with
      lipopolysaccharide (LPS), a putative mediator of alcohol effects on the liver.
      Male rats were fed an alcohol-containing liquid diet (Lieber-DeCarli) for 14-15
      weeks, injected with Escherichia coli LPS (0.8 mg x kg(-1)), and killed 24 h
      later. Blood samples were taken for determination of plasma liver enzyme
      activity, and liver samples were obtained for histologic evaluation and total RNA
      extraction. Total RNA was analyzed for gene expression (Rat Toxicology U34 Array;
      Affymetrix, Santa Clara, CA). Of 8740 genes on the microchip, 2259 were expressed
      in the liver. Seven hundred ninety-eight genes underwent significant changes
      induced by either alcohol or LPS, but listed in this article are only those that
      significantly increased or decreased expression twofold or more. The genes were
      assigned to functional groups and reviewed. Gene changes were discussed from two
      viewpoints: relevance to established hypotheses of alcohol and LPS mechanisms of
      action and revealing of novel mechanisms of alcohol-induced liver injury.
      Application of DNA microarray technology to the study of alcohol-induced liver
      injury generated novel theoretical and experimental approaches to alcohol-induced
      liver injury.

PMID- 15163561
TI  - SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in
      rats.
AB  - Anxiety-like behaviors are integral features of withdrawal from chronic ethanol
      exposure. In the experiments in the current study, we tested the hypothesis that
      anxiety can be regulated independently of other withdrawal signs and thus may be
      responsive to selective pharmacological agents. For 17 days, rats were fed
      ethanol (8-12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of
      ethanol treatment, rats were tested in either the social interaction or plus-maze
      test of anxiety-like behavior after treatment with drugs hypothesized to have
      anxiolytic action. SB242084, flumazenil, and CRA1000-antagonists for 5
      hydroxytryptamine (serotonin) (5-HT) 2C (5-HT(2C)), benzodiazepine, and
      corticotropin-releasing factor type 1 (CRF(1)) receptors, respectively-attenuated
      decreased social interaction without concomitant effects on activity measures. In
      contrast, ifenprodil, MDL 72222, and zolpidem-antagonists for N-methyl-d
      aspartate (NMDA) and 5-HT(3) receptors, and agonist for benzodiazepine type 1
      receptors, respectively-did not share this effect. Results for SB242084,
      flumazenil, and ifenprodil in the elevated plus-maze test were comparable to
      those in the social interaction test. These results support the suggestion that
      multiple neuronal systems (CRF(1), 5-HT(2C), and benzodiazepine receptors)
      contribute to the ethanol withdrawal sign of decreased social interaction.
      Furthermore, the selective effects of pharmacological agents on social
      interaction seem to indicate that this behavior can be dissociated from other
      signs. Because anxiety may be a complicating factor in alcohol withdrawal and
      relapse, future studies of this type are needed to provide focus for the effort
      to define selective and novel antianxiety agents for these disorders.

PMID- 15163563
TI  - Effects of ethanol on cultured embryonic neurons from the cerebral cortex of the
      rat.
AB  - Fetal alcohol syndrome is a serious disorder that causes lifelong learning,
      memory, and behavioral problems. In the current study, we determined the ethanol
      concentrations that produced detrimental effects on the development of embryonic
      cortical neurons because mental capacity seems to be proportional to the level of
      dendritic arborization. Neurons from fetal rat cortices were grown in culture in
      close proximity to a glial plane. The cells were treated with concentrations of
      ethanol ranging from 450 nM to 45 mM, and neurite outgrowth was subsequently
      quantified. A significant decrease in dendritic branching was observed at ethanol
      concentrations as low as 45 microM after 6 days of ethanol exposure in vitro,
      whereas changes in primary neurite outgrowth were observed at an ethanol
      concentration of 4.5 microM. This finding is of particular interest as it seems
      to indicate that occasional ethanol exposure is detrimental to cortical
      development at very low concentrations of ethanol.

PMID- 15163565
TI  - Characterizing the ontogeny of ethanol-associated increases in corticosterone.
AB  - The following experiments were conducted as adjuncts to previous work in an
      effort to characterize the ontogenetic profile of the elevations in
      corticosterone after ethanol challenge. In Experiment 1, female and male Sprague
      Dawley rats were administered intraperitoneally either a 1.5- or a 4.5-g/kg dose
      of ethanol on postnatal day (PND) 16, 26, 36, or 56. Blood samples were collected
      at 40, 80, or 160 min after ethanol injection and analyzed by means of
      radioimmunoassay for corticosterone levels and correlated with brain alcohol
      levels (BrALs) determined from brain samples collected at the same time
      intervals. In Experiment 2, the ethanol dose was varied ontogenetically to equate
      functional impairment across age, with the use of intraperitoneal doses of
      ethanol of 3.2, 2.6, or 2.2 g/kg, to induce equivalent amounts of ethanol-induced
      motor impairment in infant (PND 22), adolescent (PND 28), or adult (PND 60) rats,
      respectively. Animals were tested on a swim task 15 min after injection, with
      blood and brain samples collected immediately after the swim and analyzed for
      corticosterone levels and BrALs as in Experiment 1. Reminiscent of previous
      reports of an age-related increase in sensitivity to the hypnotic and motor
      impairing effects of ethanol, the corticosterone response to an ethanol challenge
      increased at least through adolescence, with sex differences emerging by PND 26
      and becoming more pronounced in adulthood. To the extent that corticosterone
      release is involved in the reinforcing effects of drugs, ontogenetic differences
      in the response of the hypothalamic-adrenal-pituitary (HPA) axis to ethanol could
      contribute to the excessive alcohol consumption often observed during
      adolescence.

PMID- 15163564
TI  - Involvement of the mesopallidal dopamine system in ethanol reinforcement.
AB  - The current study was designed to test the hypothesis that acquisition of signal
      induced anticipation of self-administered ethanol and operant oral self
      administration of ethanol increases the extracellular levels of dopamine in the
      ventral pallidum of alcohol-preferring (P) rats. The study was also designed to
      explore the association between behavioral activity and dopamine efflux in the
      ventral pallidum. Adult, female P rats were randomly assigned to operantly self
      administer 15% (volume/volume) ethanol, 0.0125% (weight/volume) saccharin, or
      water. In addition, all groups were acclimated in the operant chambers to periods
      of habituation, anticipation, and postadministration. The ethanol group showed
      significant increases in extracellular levels of dopamine in the ventral pallidum
      during (1). the first 10 min of the anticipation period, (2). the last 10 min of
      the self-administration period, and (3). the initial 10 min of the
      postadministration period. There were no significant differences in motor
      activity during anticipation and self-administration of ethanol, saccharin, or
      water. These findings support the suggestion that dopaminergic activation in the
      ventral pallidum is involved in ethanol-seeking and ethanol-drinking behaviors
      and directly implicate the mesopallidal dopamine system in the reinforcing
      actions of ethanol.

PMID- 15163566
TI  - Role of high normal gamma-glutamyltransferase level in identifying heavy alcohol
      use in young men.
AB  - The objective of the current study was to determine the predictive value of high
      normal gamma-glutamyltransferase (GGT) level as an indication of heavy drinking
      in young men. In a sample of 577 men attending a one-day army recruitment process
      mandatory for all Swiss men at age 19 years, GGT level was evaluated as the
      dependent variable for each of eight dichotomous classifications of individuals
      on the basis of meeting cut-off criteria for five indexes of alcohol use, two
      indexes of alcohol-related problems, and one index of body mass. The sensitivity,
      specificity, and predictive values of GGT level in identifying subjects as either
      heavy drinkers or being overweight were determined. Compared with findings for
      their counterparts, GGT level was higher in subjects reporting consumption of
      more than 14 drinks per week (20.5 +/- 7.81 vs. 18.9 +/- 7.60, P <.05), in those
      reporting being drunk at least once during the past 30 days (20.3 +/- 7.80 vs.
      18.3 +/- 7.43, P <.001), and in individuals with body mass indexes >or=25 kg/m(2)
      (25.8 +/- 10.84 vs. 18.3 +/- 6.59, P <.001). At a GGT level cut-off of 20 U/l,
      the sensitivity, specificity, and positive and negative predictive values of
      either being a heavy drinker or overweight were 48.2%, 70.2%, 67.7%, and 51.2%,
      respectively. Exclusion of subjects with body mass indexes of >or=25 kg/m(2)
      revealed similar results. High normal GGT level in young men is indicative of
      heavy alcohol use or being overweight; when present, subjects should be screened
      further for potential concomitant drinking problems.

PMID- 15163567
TI  - An introduction to wilderness medicine.
AB  - As individuals increasingly recreate in wilderness settings, the medical
      community is faced with increasing numbers of injuries and illnesses occurring in
      remote and austere locations. In response to this, the specialized and dynamic
      field of wilderness medicine has developed to care for and counsel those
      participating in wilderness pursuits. This article adds clarity to the definition
      of wilderness medicine and examines the current state of wilderness medicine,
      including the scope of practice in the United States.

PMID- 15163568
TI  - Hypothermia and localized cold injuries.
AB  - Hypothermia and localized cold injuries are largely preventable with proper
      preparation for activities in cold environments. Proficient field management is
      crucial to the final outcome in terms of function and viability because proper
      care is vital to preventing exacerbation of the initial exposure and injury.
      Rapid rewarming is optimal when further cold exposure can be avoided reliably.
      Repetitive freeze-thaw cycles are associated with increased morbidity and tissue
      loss caused by progressive microvascular injury and thrombosis. The subsequent
      care is largely supportive and consists of wound care and physical and
      hydrotherapy to promote optimal functional recovery.

PMID- 15163569
TI  - Plant exposures: wilderness medicine.
AB  - This article discusses poisonous plants, the symptoms that might arise if they
      are ingested, and the treatments that should be administered to patients.

PMID- 15163570
TI  - Heat-related illness.
AB  - Heat-related illness represents a continuum of disorders from minor syndromes
      such as heat cramps, heat syncope, and heat exhaustion to the severely life
      threatening disorder known as heat stroke. It represents an important cause of
      wilderness-related morbidity and mortality.

PMID- 15163571
TI  - High-altitude illness.
AB  - Travel to a high altitude requires that the human body acclimatize to hypobaric
      hypoxia. Failure to acclimatize results in three common but preventable maladies
      known collectively as high-altitude illness: acute mountain sickness (AMS), high
      altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE).
      Capillary leakage in the brain (AMS/HACE) or lungs (HAPE) accounts for these
      syndromes. The morbidity and mortality associated with high-altitude illness are
      significant and unfortunate, given they are preventable. Practitioners working in
      or advising those traveling to a high altitude must be familiar with the early
      recognition of symptoms, prompt and appropriate therapy, and proper preventative
      measures for high-altitude illness.

PMID- 15163572
TI  - Submersion.
AB  - Many thousands of individuals are submersion victims each year in the United
      States. The majority of victims are young, previously healthy people. There have
      been no recent breakthroughs in medical technology or treatment modalities that
      have improved survival rates for submersion victims. The key to their successful
      outcome and return to productive, full lives is aggressive resuscitation by
      emergency physicians and prehospital care providers. Most submersion incidents
      should never take place. Emergency physicians can take the lead in public
      education and prevention.

PMID- 15163573
TI  - Lightning injuries.
AB  - Lightning is persistently one of the leading causes of death caused by
      environmental or natural disaster. To understand the pathophysiology and
      treatment of lightning injuries one must first discount the innumerable myths,
      superstitions, and misconceptions surrounding lightning. The fundamental
      difference between high voltage electrical injury and lightning is the duration
      of exposure to current. Reverse triage should be instituted in lightning strike
      victims because victims in cardiopulmonary arrest might gain the greatest benefit
      from resuscitation efforts, although there is no good evidence suggesting that
      lightning strike victims might benefit from longer than usual resuscitation
      times. Many of the injuries suffered by lightning strike victims are unique to
      lightning, and long-term sequelae should be anticipated and addressed in the
      lightning victim.

PMID- 15163574
TI  - Arachnid envenomation.
AB  - This article focuses on the medically relevant arachnid species found in North
      America and selected other arachnids from around the world. While it is largely
      still true that the geographic location of the envenomation assists in
      determining the species responsible, the booming trade in arachnids as exotic
      pets should prompt the clinician to inquire into this possibility. Expert advice
      should be sought in either case; species identification is critical in
      determining the need for and proper type of antivenom therapy.

PMID- 15163575
TI  - North American snake envenomation: diagnosis, treatment, and management.
AB  - A bite from a venomous snake is a medical emergency involving not only the
      affected site but also multiple organ systems. Rapid transport of a snakebite
      victim to a medical facility is paramount. Management decisions must be based on
      close clinical monitoring of the potentially erratic envenomation syndrome.
      Because of the many variables inherent in the management of snakebite victims,
      consultation with a physician specialist is recommended.

PMID- 15163576
TI  - North American wild mammalian injuries.
AB  - Wild animal injuries are distinct from other injuries sustained by humans;
      tearing, cutting, penetrating, and crushing injuries are sometimes combined with
      falls and large animal forces causing blunt trauma. Bites from attacking animals
      may cause local infection, and wounds are potentially contaminated with a variety
      of pathogens. In addition, animals can transmit systemic diseases, many of which
      induce substantial morbidity and mortality. To compound the problem, many animal
      attacks occur in remote or wilderness areas and involve substantial delays in the
      time to notification, rescue, and presentation to definitive care. This article
      discusses attacks by the most common North American wild mammals.

PMID- 15163577
TI  - Wilderness survival.
AB  - This introduction to wilderness survival discusses basic survival rules and
      psychology, essential equipment, and selected survival skills, including shelter
      building, fire starting, water acquisition, signaling, and navigation. Among the
      litany of other survival topics in the literature, these skills are the most
      important. An effort has been made to concentrate on the skills and lessons that
      are simple, straightforward, and most easily used in a wilderness emergency. The
      purpose is to help readers to learn how to survive with the least amount of pain
      and the greatest possibility of success.

PMID- 15163578
TI  - An introduction to mountain search and rescue.
AB  - Alpine search and rescue teams must perform each incident response safely. To do
      so requires experience, organizational skills, technical training, and ability.
      In addition, teams should interface with emergency medical control advisors who
      are familiar with local terrain, mountain rescue operations, and the evacuation
      techniques employed. To facilitate safety and organization, each mission can be
      divided into four linked stages: location, reach, stabilize, and evacuate.

PMID- 15163579
TI  - Wilderness emergency medical services.
AB  - Emergency medical service providers are increasingly being asked to respond to
      unfamiliar environments. The challenges encountered have spurred the development
      of courses designed to enhance the rescuer's knowledge about wilderness medical
      topics and how to work and travel safely in a hitherto unfamiliar environment.
      This article describes the evolution of these courses, discusses the challenges
      of curriculum development, and lists some of what is available.

PMID- 15163580
TI  - Wilderness medicine education for the physician.
AB  - As more Americans venture into the wilderness, physicians will be called upon to
      provide care in the backcountry or austere setting. Additionally, more isolated
      regions of the world are becoming accessible for trekking and mountaineering.
      These facts imply a higher rate of injuries and medical problems within a
      distinct spectrum of disease that are best treated by the well-prepared and
      continuously educated physician. This article discusses the educational resources
      that are currently available for physicians to meet these needs in the United
      States.

PMID- 15163581
TI  - Wilderness emergency medical services systems.
AB  - Wilderness emergency medical services (WEMS) systems have components and
      requirements that are different from those of traditional EMS systems. These
      differences arise from the extremes of time and environmental exposure and the
      limited available resources that help define the wilderness environment. Although
      disaster systems combine wilderness and traditional EMS system components, most
      WEMS systems have had to develop independently on a localized level and in
      response to the need of a particular community or location. In many cases,
      volunteers provide much of the personnel and resources available to law
      enforcement agencies that are ultimately tasked with the responsibility of
      oversight for effecting rescues in a wilderness setting.

PMID- 15163583
TI  - Characterization of an E2-type colicin and its application to treat alfalfa seeds
      to reduce Escherichia coli O157:H7.
AB  - Several outbreaks of Escherichia coli O157:H7 infections have been associated
      with contaminated alfalfa seeds. A recently isolated E. coli strain Hu194 was
      capable of inhibiting 22 strains of E. coli O157:H7 and this inhibition was
      mediated by the production of a colicin named Hu194. The objectives of this study
      were to test the efficacy of treating alfalfa seeds with colicin Hu194 against E.
      coli O157:H7 strains, and to characterize this antimicrobial protein. Significant
      reductions (approximately 5 log CFU ml-1) in the viable cell counts of strains
      43890 and 43895 were observed after 1-day incubation with semi-crude colicin, and
      after 2 days for strain 3081. Strain 43890 was successfully eliminated (5 log CFU
      g-1) from inoculated alfalfa seeds after soaking in a colicin suspension at a
      concentration of 10,000 AU/g. Treatment of alfalfa seeds inoculated with strains
      43895 and 3081 required 20-fold higher concentrations of colicin Hu194 to achieve
      as much as 3 log CFU g-1 reductions. The genes encoding the colicin Hu194 operon
      were located on a 6 kb plasmid, and the sequence analysis revealed that this
      colicin was an E-type DNAse. From the sequence data, the estimated molecular
      masses of colicin Hu194, its immunity protein and lysis protein were 61.3, 10.0
      and 4.8 kDa, respectively. Based on DNA and protein sequence comparisons with
      other E-type colicin, colicin Hu194 belonged to the type E2-colicin cluster.
      However, cross-immunity tests between E-group colicins suggested that Hu194
      colicin was divergent from the previously characterized E2 colicins.

PMID- 15163585
TI  - Use of RAPD-PCR as a method to follow the progress of starter cultures in
      sauerkraut fermentation.
AB  - DNA fingerprinting methods were used to follow the progress of unmarked starter
      cultures in laboratory sauerkraut fermentations (1.2 and 13 l). Random prime PCR
      (RAPD-PCR) was used for strain-specific identification of Leuconostoc
      mesenteroides cultures. A comparative analysis of RAPD banding patterns for
      fermentation isolates and starter cultures was carried out using both genetically
      marked and unmarked cultures. While some variation in the RAPD patterns was
      observed, the results showed that the starter cultures dominated the fermentation
      during early heterofermentative stage for up to 5 days after the start of
      fermentation. Results from marked and unmarked starter cultures were confirmed by
      intergenic transcribed spacer (ITS)-PCR, and strain identify was confirmed by
      pulse field gel electrophoresis (PFGE) patterns. The results demonstrate the
      utility of RAPD to follow the progression of unmarked starter cultures of L.
      mesenteroides in sauerkraut fermentations.

PMID- 15163584
TI  - Protective effect of exopolysaccharide colanic acid of Escherichia coli O157:H7
      to osmotic and oxidative stress.
AB  - Many strains of Escherichia coli O157:H7 produce, under stress, an
      exopolysaccharide (EPS) comprised of colanic acid (CA) and form mucoid colonies
      on minimal glucose agar (MGA) at ambient temperature. Previous research conducted
      in our laboratory involving a CA-proficient (W6-13) and a CA-deficient (M4020;
      wcaD::Ekan(r)) strain of E. coli O157:H7 revealed that CA conferred acid and heat
      tolerance to E. coli O157:H7. Cells covered with CA were more persistent during
      acid (pH 4.5, 5.5, and 6.5) and heat (55 and 60 degrees C) treatment. The goal of
      this research was to study the effect of CA on the fate of E. coli O157:H7 under
      osmotic and oxidative stress. Cells of W6-13 and M4020 were exposed to various
      concentrations of NaCl (0.5, 1.5, and 2.5 M) and H2O2 (0, 10, and 20 mM) in
      minimal glucose broth (MGB) at 22 degrees C. Viable counts of E. coli O157:H7
      were determined within 48 h of the osmotic stress and 3 h of the oxidative
      stress. The results suggest that cells of E. coli O157:H7 deficient in CA
      production are more susceptible than its wild-type parent to NaCl ( P< 0.05) and
      H2O2 (P< or = 0.05). This indicates that CA plays a role in protecting E. coli
      O157:H7 from osmotic and oxidative stress.

PMID- 15163586
TI  - Sodium bicarbonate enhances biocontrol efficacy of yeasts on fungal spoilage of
      pears.
AB  - The addition of 2% (w/v) sodium bicarbonate (SBC) in the suspensions of
      antagonistic yeast Cryptococcus laurentii or Trichosporon pullulans significantly
      limited spore germination and germ tube elongation of Penicillium expansum and
      Alternaria alternata in potato dextrose broth (PDB) medium. Biocontrol activity
      of C. laurentii or T. pullulans against postharvest decay caused by P. expansum
      and A. alternata in pear fruits was significantly increased when C. laurentii or
      T. pullulans combined with SBC. Combining C. laurentii or T. pullulans with SBC
      provided a more effective control on P. expansum and A. alternata than applying
      the antagonistic yeast or SBC alone. Effects of C. laurentii with and without SBC
      on controlling P. expansum and A. alternata were better than those of T.
      pullulans. C. laurentii in combination with SBC showed the best control of
      disease caused by A. alternata in pear fruits.

PMID- 15163587
TI  - Temperature step changes: a novel approach to control biofilms of Streptococcus
      thermophilus in a pilot plant-scale cheese-milk pasteurisation plant.
AB  - A pilot plant-scale cheese-milk pasteurisation plant was designed and constructed
      to study the development of biofilms of Streptococcus thermophilus during
      pasteurisation of milk, and to investigate methods for preventing this growth
      from occurring. Under base run conditions, S. thermophilus grew on surfaces in
      the cool-down sections of the pilot plant, between 50 and 35 degrees C (bulk milk
      temperature), and could be detected in the product stream after 8-10 h
      production, reaching levels of 10(6) CFU ml-1 after 16 h. Thermoduric bacteria
      also grew in the heating sections of the pilot plant, although to a lesser
      extent, as did non-thermoduric bacteria that originated in the raw milk. The
      novel application of temperature step changes, implemented periodically to the
      growth region of S. thermophilus, successfully controlled the development of
      biofilms of these organisms. The growth of bacteria on the heating side of the
      pilot plant was also prevented by the implementation of these same step changes.
      The optimum step change conditions required to achieve a 20-h production run
      without detectable growth of S. thermophilus comprised a step change to 55
      degrees C, applied for 10 min, with a 60-min interval between step changes.

PMID- 15163588
TI  - Investigation of the effectiveness of Ascopyrone P as a food preservative.
AB  - Ascopyrone P (APP), a novel antibacterial from fungi, was evaluated as a food
      preservative. Efficacy was generally assessed by comparing the time taken for
      test strains to grow to 10(6) CFU/g in food +/- APP. In chilled chicken soup,
      2000 mg kg-1 APP prevented Bacillus cereus, Listeria monocytogenes, Pseudomonas
      fluorescens, Salmonella and Escherichia coli reaching this threshold for >60
      days. Good activity was also observed at 500-1000 mg kg-1 but not against L.
      monocytogenes. No activity was observed against Saccharomyces cerevisiae.
      Activity was reduced at 20 degrees C, although 2000 mg kg-1 was still effective
      against B. cereus and P. fluorescens. APP was less effective in chilled cooked
      meat systems and ineffective in raw meat. In a cooked meat system at 8 degrees C,
      bacteriostatic effect was generally observed at 2000 mg kg-1 against Salmonella
      typhimurium, E. coli and P. fluorescens but not against L. monocytogenes or
      Lactobacillus sake. Activity against Gram-negative enteric bacteria was enhanced
      by low temperature. In milk, 2000 mg l-1 was effective against P. fluorescens at
      chilled but not ambient temperature. APP was ineffective against yeasts and the
      mould Byssochlamys in apple juice. A minimum of 2000 mg kg-1 APP would appear to
      be necessary for antibacterial efficacy in food, although low-temperature storage
      may help. Observed variations in sensitivity may be related to APP stability,
      which decreases >pH 5.5. Toxicology testing is needed before consideration of APP
      for food use.

PMID- 15163589
TI  - New method for rapid and sensitive quantification of sulphide-producing bacteria
      in fish from arctic and temperate waters.
AB  - The offensive, fishy, rotten H2S-off-odours in spoiled, aerobically and cold
      stored fish from arctic and temperate waters are generally caused by sulphide
      producing bacteria (SPB), mainly Shewanella putrefaciens. In the present work, a
      new, rapid, simple and accurate method for estimation of the SPB content in fish
      from these areas is described. The quantification is based on the formation rate
      of iron sulphide during growth of SPBs incubated at 30 degrees C in a liquid
      growth medium containing cysteine, sodium thiosulphate and iron(III)citrate as
      specific substrates for iron sulphide formation. The iron sulphide turns the
      medium grey and masks the background fluorescence in the medium when the SPB
      content in the assay is approximately 10(9) cfu/ml. The fluorescence change could
      be detected instrumentally and the colour change visually. The method was
      developed and evaluated in tests with S. putrefaciens CCUG 13452 DT as well as
      naturally occurring SPBs in cod, salmon, wolf fish and coal fish. A linear
      correlation between the SPB count and detection time was obtained over the entire
      range from 1 to 10(9) cfu SPB/g, corresponding to detection times 17 and 1 h,
      respectively. The correlation is described by the equation: log cfu/g fish= 
      0.59(+/- 0.17) x DT+ 9.65(+/- 0.09), where DT is the detection time in hours. The
      model was valid for all the tested fish species and all tested naturally
      occurring SPBs in these species. The regression coefficients (R2) for cod, coal
      fish, wolf fish and salmon were 0.99, 0.92, 0.97 and 0.97, respectively. The
      detection level of the method is 1 SPB per sample tube, corresponding to 16 cfu/g
      fish. The method could be used to predict the remaining shelf life of the fish
      for different markets, even when the time-temperature history during storage of
      the fish is unknown.

PMID- 15163590
TI  - Enhancement of 2-methylbutanal formation in cheese by using a fluorescently
      tagged Lacticin 3147 producing Lactococcus lactis strain.
AB  - The amino acid conversion to volatile compounds by lactic acid bacteria is
      important for aroma formation in cheese. In this work, we analyzed the effect of
      the lytic bacteriocin Lacticin 3147 on transamination of isoleucine and further
      formation of the volatile compound 2-methylbutanal in cheese. The Lacticin 3147
      producing strain Lactococcus lactis IFPL3593 was fluorescently tagged (IFPL3593
      GFP) by conjugative transfer of the plasmid pMV158GFP from Streptococcus
      pneumoniae, and used as starter in cheese manufacture. Starter adjuncts were the
      bacteriocin-sensitive strains L. lactis T1 and L. lactis IFPL730, showing
      branched chain amino acid aminotransferase and alpha-keto acid decarboxylase
      activity, respectively. Adjunct strains were selected to complete the isoleucine
      conversion pathway and, hence, increase formation of 2-methylbutanal conferring
      aroma to the cheese. The non-bacteriocin-producing strain L. lactis IFPL359-GFP
      was included as starter in the control batch. Fluorescent tagging of the starter
      strains allowed their tracing in cheese during ripening by fluorescence
      microscopy and confocal scanning laser microscopy. The bacteriocin produced by L.
      lactis IFPL3593-GFP enhanced lysis of the adjuncts with a concomitant increase in
      isoleucine transamination and about a two-fold increase of the derived volatile
      compound 2-methylbutanal. This led to an enhancement of the cheese aroma detected
      by a sensory panel. The improvement of cheese flavour and aroma may be of
      significant importance for the dairy industry.

PMID- 15163592
TI  - Screening the receptorome to discover the molecular targets for plant-derived
      psychoactive compounds: a novel approach for CNS drug discovery.
AB  - Because psychoactive plants exert profound effects on human perception, emotion,
      and cognition, discovering the molecular mechanisms responsible for psychoactive
      plant actions will likely yield insights into the molecular underpinnings of
      human consciousness. Additionally, it is likely that elucidation of the molecular
      targets responsible for psychoactive drug actions will yield validated targets
      for CNS drug discovery. This review article focuses on an unbiased, discovery
      based approach aimed at uncovering the molecular targets responsible for
      psychoactive drug actions wherein the main active ingredients of psychoactive
      plants are screened at the "receptorome" (that portion of the proteome encoding
      receptors). An overview of the receptorome is given and various in silico, public
      domain resources are described. Newly developed tools for the in silico mining of
      data derived from the National Institute of Mental Health Psychoactive Drug
      Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail.
      Additionally, three case studies aimed at discovering the molecular targets
      responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica
      actions are presented. Finally, recommendations are made for future studies.

PMID- 15163593
TI  - Clinical investigations of the therapeutic potential of ayahuasca: rationale and
      regulatory challenges.
AB  - Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and
      shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the
      oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results
      from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is
      the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long
      been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it
      is used as a sacrament by several syncretic churches. Some of these organizations
      have incorporated in the United States. The recreational and religious use of
      ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is
      increasing. The current legal status of ayahuasca or its source plants in the
      United States is unclear, although DMT is a Schedule I controlled substance. One
      ayahuasca church has received favorable rulings in 2 federal courts in response
      to its petition to the Department of Justice for the right to use ayahuasca under
      the Religious Freedom Restoration Act. A biomedical study of one of the churches,
      the Uniao do Vegetal (UDV), indicated that ayahuasca may have therapeutic
      applications for the treatment of alcoholism, substance abuse, and possibly other
      disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca
      can be used safely in normal healthy adults, but have done little to clarify its
      potential therapeutic uses. Because of ayahuasca's ill-defined legal status and
      variable botanical and chemical composition, clinical investigations in the
      United States, ideally under an approved Investigational New Drug (IND) protocol,
      are complicated by both regulatory and methodological issues. This article
      provides an overview of ayahuasca and discusses some of the challenges that must
      be overcome before it can be clinically investigated in the United States.

PMID- 15163594
TI  - Hallucinogens and dissociative agents naturally growing in the United States.
AB  - It is usually believed that drugs of abuse are smuggled into the United States or
      are clandestinely produced for illicit distribution. Less well known is that many
      hallucinogens and dissociative agents can be obtained from plants and fungi
      growing wild or in gardens. Some of these botanical sources can be located
      throughout the United States; others have a more narrow distribution. This
      article reviews plants containing N,N-dimethyltryptamine, reversible type A
      monoamine oxidase inhibitors (MAOI), lysergic acid amide, the anticholinergic
      drugs atropine and scopolamine, or the diterpene salvinorin-A (Salvia divinorum).
      Also reviewed are mescaline-containing cacti, psilocybin/psilocin-containing
      mushrooms, and the Amanita muscaria and Amanita pantherina mushrooms that contain
      muscimol and ibotenic acid. Dangerous misidentification is most common with the
      mushrooms, but even a novice forager can quickly learn how to properly identify
      and prepare for ingestion many of these plants. Moreover, through the ever
      expanding dissemination of information via the Internet, this knowledge is being
      obtained and acted upon by more and more individuals. This general overview
      includes information on the geographical range, drug content, preparation,
      intoxication, and the special health risks associated with some of these plants.
      Information is also offered on the unique issue of when bona fide religions use
      such plants as sacraments in the United States. In addition to the Native
      American Church's (NAC) longstanding right to peyote, two religions of Brazilian
      origin, the Santo Daime and the Uniao do Vegetal (UDV), are seeking legal
      protection in the United States for their use of sacramental dimethyltryptamine
      containing "ayahuasca."

PMID- 15163595
TI  - Prostacyclin and its analogues in the treatment of pulmonary hypertension.
AB  - Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess
      antithrombotic and antiproliferative properties. All of these properties help to
      antagonize the pathological changes that take place in the small pulmonary
      arteries of patients with pulmonary hypertension. Indeed, several prostanoids
      have been shown to be efficacious to treat pulmonary hypertension, while the main
      mechanism underlying the beneficial effects remains unknown. There are
      indications of beneficial combination effects of prostaglandins and
      phosphodiesterase inhibitors and endothelin receptor antagonists. This speaks in
      favor of combination therapies for pulmonary hypertension in the future. The mode
      of application of prostanoids used in randomized controlled studies has been
      quite variable: continuous i.v. infusion of prostacyclin, continuous s.c.
      infusion of treprostinil, p.o. application of beraprost, and inhaled application
      of iloprost. In addition, the applied doses were quite different, ranging from
      0.25 ng/kg/min for inhaled iloprost to 30-50 ng/kg/min for i.v. prostacyclin.
      While the principal pharmacological properties of all prostanoids are very
      similar due to a main action on IP receptors, there are considerable differences
      in pharmacokinetics and metabolism, with half-lives of 2 min for prostacyclin and
      about 34 min for treprostinil for i.v. infused drugs and half-lives of about 85
      min for s.c. infused treprostinil. In addition, the adverse effects largely
      depend on the doses used and the mode of application, although there is great
      variability between subjects. It remains to be determined which patients will
      profit most from which substance (or combination) and mode of application.

PMID- 15163596
TI  - Rationale for and use of NMDA receptor antagonists in Parkinson's disease.
AB  - N-Methyl-d-aspartate (NMDA) glutamate receptors are a class of excitatory amino
      acid receptors, which have several important functions in the motor circuits of
      the basal ganglia, and are viewed as important targets for the development of new
      drugs to prevent or treat Parkinson's disease (PD). NMDA receptors are ligand
      gated ion channels composed of multiple subunits, each of which has distinct
      cellular and regional patterns of expression. They have complex regulatory
      properties, with both agonist and co-agonist binding sites and regulation by
      phosphorylation and protein-protein interactions. They are found in all of the
      structures of the basal ganglia, although the subunit composition in the various
      structures is different. NMDA receptors present in the striatum are crucial for
      dopamine-glutamate interactions. The abundance, structure, and function of
      striatal receptors are altered by the dopamine depletion and further modified by
      the pharmacological treatments used in PD. In animal models, NMDA receptor
      antagonists are effective antiparkinsonian agents and can reduce the
      complications of chronic dopaminergic therapy (wearing off and dyskinesias). Use
      of these agents in humans has been limited because of the adverse effects
      associated with nonselective blockade of NMDA receptor function, but the
      development of more potent and selective pharmaceuticals holds the promise of an
      important new therapeutic approach for PD.

PMID- 15163597
TI  - The development of successful tracheoesophageal voice restoration.
AB  - Effective treatment for laryngeal cancer concerns the preservation of voice.
      Progress has been made in treatment, rehabilitation,restoration of the airway,
      and nonsurgical treatments. With the introduction of tracheoesophageal speech and
      the voice prosthesis,many treated patients acquire socially acceptable speech
      after total laryngectomy and maintain satisfactory quality of life.

PMID- 15163598
TI  - Preoperative evaluation for tracheoesophageal voice restoration.
AB  - Systematic preoperative assessment by the surgeon and speech pathologist reduces
      complications and increases the success rates of tracheoesophageal (TE) voice
      restoration by identifying unsuitable candidates for the procedure. Preselection
      criteria are based on the various medical, psychologic, structural, and
      physiologic factors that are contraindications to the procedure or are associated
      with failure of the TE method. Predictive testing as part of the preoperative
      evaluation for secondary voice restoration can identify patients with structural
      or physiologic abnormalities that will hinder the development of satisfactory TE
      speech. Early recognition and management of potential obstacles to TE voice
      production will shorten the recovery time to achieve functional communication,and
      allow more laryngectomees to benefit from the TE voice restoration method of
      alaryngeal communication.

PMID- 15163599
TI  - Tracheoesophageal voice restoration with total laryngectomy.
AB  - Tracheoesophageal voice restoration has gained worldwide acceptance over the past
      24 years and is the preferred method of postlaryngectomy speech.
      Tracheoesophageal puncture is safe, reliable,and reproducible and should be
      considered in all patients undergoing total laryngectomy and in those who have
      failed to master other methods of alaryngeal speech. This article discusses
      patient selection, surgical technique and complications, quality of speech,and
      predictors of success. Improved prosthesis design has expanded the use of
      tracheoesophageal speech in laryngectomees.

PMID- 15163600
TI  - Operative prevention and management of voice-limiting pharyngoesophageal spasm.
AB  - Voice-limiting pharyngoesophageal spasm presents a challenge to the surgeon who
      is trying to optimize functional voice outcomes in the laryngectomy patient.
      Modified closure techniques, adjunctive myotomy, and pharyngeal plexus neurectomy
      have the ability to improve or prevent pharyngoesophageal spasm. Attempts to
      maximize vocal outcome should be considered at the original time of laryngectomy
      and tracheoesophageal voice restoration because salvage treatment can be
      challenging.

PMID- 15163601
TI  - Management of pharyngoesophageal spasm with Botox.
AB  - Pharyngoesophageal spasm following laryngectomy can result in failure of
      tracheoesophageal (TE) speech and dysphagia. Chemical denervation with
      Clostridium botulinum toxin (Botox) is effective in relieving pharyngeal
      constrictor spasm, thereby facilitating TE speech production. This article
      reviews the technique, results,and complications regarding the use of Botox in
      the management of TE speech failure associated with pharyngoesophageal spasm.

PMID- 15163602
TI  - Tracheoesophageal speech following laryngopharyngectomy and pharyngeal
      reconstruction.
AB  - Voice restoration following total laryngectomy and pharyngeal reconstruction is
      an achievable yet challenging reconstructive task. Because numerous methods exist
      for pharyngeal reconstruction in conjunction with total laryngectomy, a thorough
      knowledge of the tissues used for reconstruction is necessary. This knowledge
      allows for realistic expectations for patient success. Also, specific
      modifications in voice restoration may be necessary with individual
      reconstruction methods. This article reviews the methods for reconstruction and
      the available literature on voice restoration in reconstructed patients.

PMID- 15163603
TI  - Nonsurgical management of the stoma to maximize tracheoesophageal speech.
AB  - The anatomic site for respiratory exchange following total laryngectomy is the
      tracheostoma, which plays a key role in restoring pulmonary function in all
      laryngectomized patients and in restoring speech in patients who use
      tracheoesophageal (TE) voice production. Variations in stomal size, shape, and
      location are challenges in restoring speech and pulmonary function following
      total laryngectomy and TE puncture. A large, irregularly shaped, or recessed
      stoma that prevents adequate stomal occlusion or a small stoma that inhibits
      placement of a TE voice prosthesis is frustrating to the patient and requires
      creative management strategies. This article discusses the problems of stomal
      size, configuration, and location as they relate to TE voice restoration and
      reviews the nonsurgical strategies and techniques used to manage these problems.

PMID- 15163604
TI  - Voice following laryngeal cancer surgery: troubleshooting common problems after
      tracheoesophageal voice restoration.
AB  - The introduction of tracheoesophageal voice restoration by Blom and Singer has
      provided laryngectomy patients with a successful alternative to the use of
      artificial larynx and esophageal speech. Although this method of communication
      provides for the rapid acquisition of intelligible, functional speech, there are
      common problems that may occur in these patients. Close follow-up of patients
      postoperatively along with thorough patient education is beneficial to improving
      long-term success with tracheoesophageal speech. The purpose of this article is
      to discuss common problems encountered in the treatment of patients who have
      undergone tracheoesophageal puncture and to provide systematic assessment and
      treatment guidelines that are essential to maintaining functional
      tracheoesophageal speech.

PMID- 15163605
TI  - Nontracheoesphageal speech rehabilitation.
AB  - Numerous noninvasive methods exist for successful voice rehabilitation following
      total laryngectomy. In addition to surgical voice restoration, practitioners
      caring for laryngectomee patients should understand the esophageal speech methods
      and the available electronic devices, so informed decisions can be made on
      individualized needs and abilities.

PMID- 15163606
TI  - Optimizing voice after endoscopic partial laryngectomy.
AB  - Phonosurgical management of early and midsized glottic cancer has evolved
      considerably during the past decade. There has been a partial migration from
      transcervical to transoral partial laryngectomy to diminish perioperative
      morbidity (ie, tracheotomy) and to facilitate subsequent voice restoration. After
      an endoscopic partial laryngectomy heals, a medialization of the glottal neocord
      should be done. An endolaryngeal injection or transcervical medialization is used
      to reconstruct the glottal valve and the associated aerodynamic competency, which
      ultimately enhance voice quality. These reconstructive techniques will improve
      the voice outcome subsequent to almost any endoscopic vertical partial
      laryngectomy; however,a near-normal conversational level voice can be achieved
      inpatients in whom there is one remaining normal vocal fold. These favorable
      results are based on the fact that after effective glottal closure is achieved
      through the reconstruction, the primary oscillator is the layered microstructure
      of noncancerous glottal tissue.

PMID- 15163607
TI  - Voice rehabilitation after external partial laryngeal surgery.
AB  - Excising part or all of a larynx as a cancer operation results in changes that
      transgress anatomic, physiologic, psychologic, and social common principles. The
      treatment of laryngeal cancer has evolved significantly over the prior 5 decades,
      and better diagnostic procedures, combined with an improved understanding of the
      anatomico-clinical behavior of laryngeal tumors, has allowed the development of
      external partial or "organ-preservation" laryngeal surgery. When total or partial
      laryngectomy procedures are performed,profound changes in anatomy and physiology
      and, thus,voice are inevitable. Because the spectrum of these changes maybe
      broad, the role of professional rehabilitation therapy has taken an involved,
      multidisciplinary approach, with an integrated understanding of anticipated and
      potential functional outcomes.

PMID- 15163608
TI  - Voice rehabilitation after near-total laryngectomy.
AB  - Near-total laryngectomy provides oncologic control of hypopharyngeal and
      laryngeal cancers that are not amenable to conservation procedures. The resulting
      myomucosal shunt provides a prosthesis-free method of voice rehabilitation. This
      review presents indications, technique, and speech rehabilitation for a near
      total laryngectomy.

PMID- 15163610
TI  - Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance
      imaging study.
AB  - The cognitive impairment revealed in some non- demented amyotrophic lateral
      sclerosis (ALS) patients is characterized by executive dysfunction with widely
      repeated deficits on tests of verbal (letter) fluency. However, conflicting
      evidence exists of an impairment on other word retrieval tasks, such as
      confrontation naming, which do not place heavy demands on executive processes.
      Previous research has demonstrated intact confrontation naming in the presence of
      verbal fluency deficits, although naming deficits have been described in other
      studies. In this investigation, functional MRI (fMRI) techniques were employed to
      explore whether word retrieval deficits and underlying cerebral abnormalities
      were specific to letter fluency, which are more likely to indicate executive
      dysfunction, or were also present in confrontation naming, indicating language
      dysfunction. Twenty-eight non-demented ALS patients were compared with 18 healthy
      controls. The two groups were matched for age, intelligence quotient, years of
      education, and anxiety and depression scores. Two compressed-sequence overt fMRI
      activation paradigms were employed, letter fluency and confrontation naming,
      which were developed for use with an older and potentially impaired population.
      In ALS patients relative to controls, the letter fluency fMRI task revealed
      significantly impaired activation in the middle and inferior frontal gyri and
      anterior cingulate gyrus, in addition to regions of the parietal and temporal
      lobes. The confrontation naming fMRI task also revealed impaired activation in
      less extensive prefrontal regions, including the inferior frontal gyrus and
      regions of the temporal, parietal and occipital lobes. These changes were present
      despite matched performance between patients and controls during each activation
      paradigm. The pattern of dysfunction corresponded to the presence of cognitive
      deficits on both letter fluency and confrontation naming in the ALS group. This
      study provides evidence of cerebral abnormalities in ALS in the network of
      regions involved in language and executive functions. Moreover, the findings
      further illustrate the heterogeneity of cognitive and cerebral change in ALS.

PMID- 15163611
TI  - Satisfaction of the uncertainty principle in cancer clinical trials:
      retrospective cohort analysis.
AB  - OBJECTIVE: To assess whether publicly funded adult cancer trials satisfy the
      uncertainty principle, which states that physicians should enroll a patient in a
      trial only if they are substantially uncertain which of the treatments in the
      trial is most appropriate for the patient. This principle is violated if trials
      systematically favour either the experimental or the standard treatment. DESIGN:
      Retrospective cohort study of completed cancer trials, with randomisation as the
      unit of analysis. SETTING: Two cooperative research groups in the United States.
      STUDIES INCLUDED: 93 phase III randomised trials (103 randomisations) that
      completed recruitment of patients between 1981 and 1995. MAIN OUTCOME MEASURES:
      Whether the randomisation favoured the experimental treatment, the standard
      treatment, or neither treatment; effect size (outcome of the experimental
      treatment compared with outcome of the standard treatment) for each
      randomisation. RESULTS: Three randomisations (3%) favoured the standard
      treatment, 70 (68%) found no significant difference between treatments, and 30
      (29%) favoured the experimental treatment. The average effect size was 1.20 (95%
      confidence interval 1.13 to 1.28), reflecting a slight advantage for the
      experimental treatment. CONCLUSIONS: In cooperative group trials in adults with
      cancer, there is a measurable average improvement in disease control associated
      with assignment to the experimental rather than the standard arm. However, the
      heterogeneity of outcomes and the small magnitude of the advantage suggest that,
      as a group, these trials satisfy the uncertainty principle.

PMID- 15163612
TI  - Developmental expression of three forms of gonadotropin-releasing hormone and
      ontogeny of the hypothalamic-pituitary-gonadal axis in gilthead seabream (Sparus
      aurata).
AB  - To address the complexity of the origin of the GnRH system in perciforms, we
      investigated the ontogenic expression of three GnRHs in gilthead seabream. Using
      in situ hybridization, chicken (c) GnRH-II mRNA-expressing cells were detected in
      the hindbrain at 1.5 days postfertilization (DPF) and in the midbrain at 2 DPF
      and thereafter; the hindbrain signals became undetectable after 10 DPF. Salmon
      (s) GnRH mRNA-expressing cells were first seen in the olfactory placode at 3 DPF,
      started caudal migration at 14 DPF, and reached the preoptic areas at 59 DPF.
      Seabream (sb) GnRH mRNA-expressing cells were first detected in the terminal
      nerve ganglion cells (TNgc), ventral part of the ventral telencephalon, nucleus
      preopticus parvocellularis, and thalamus at 39 DPF, and extended to the nucleus
      preopticus magnocellularis at 43 DPF, ventrolateral hypothalamus at 51 DPF, and
      nucleus lateralis tuberis and posterior tuberculum at 59 DPF. Coexpression of
      sbGnRH and sGnRH transcripts was found in the TNgc. Using real-time fluorescence
      based quantitative polymerase chain reaction, transcript levels of cGnRH-II and
      sGnRH were first detected at 1 and 1.5 DPF, respectively, and increased and
      remained high thereafter. Transcript levels of sbGnRH remained low after first
      detection at 1 DPF. Furthermore, these GnRH expression profiles were correlated
      with the expression profiles of reproduction-related genes in which at least four
      concomitant increases of GnRH, GnRH receptor, gonadotropin, gonadotropin
      receptor, and Vasa transcripts were found at 5, 8, 14, and 28 DPF. Our data
      provide an expanded view of the ontogeny of the GnRH system and reproductive axis
      in perciforms.

PMID- 15163613
TI  - Nucleoprotein transitions during spermiogenesis in mice with transition nuclear
      protein Tnp1 and Tnp2 mutations.
AB  - Chromatin remodeling during spermiogenesis is characterized by a series of
      nuclear protein replacements. Histones are replaced by transition nuclear
      proteins, which are in turn replaced by protamines. The transition nuclear
      proteins, TP1 and TP2, and the protamines, PRM1 and PRM2, are the major nuclear
      proteins involved in this process. Biochemical studies of mice with null
      mutations in one of the Tnp genes showed that the absence of one TP led to an
      apparent elevation in the amount of the remaining TP in the testis. To
      investigate the mechanism of changes of protein levels and effects of one Tnp
      mutation on other nuclear proteins, we used immunohistochemistry techniques to
      determine the distribution of these nuclear proteins. In contrast to previous
      biochemical analyses, which indicated that nuclear protein replacement was
      sequential with little overlap between the protein types, we found considerable
      overlap in the nucleoprotein types during spermiogenesis. The TPs, which appear
      in the nucleus before histone displacement is complete, were shared among
      genetically inequivalent spermatids. The absence of one TP did not affect the
      time of appearance of the other TP or of the protamines, but it did affect the
      displacement of the other TP, leading to its abnormal retention in the nucleus.
      The elevated levels of the remaining TP in Tnp-mutant mice appeared to be a
      consequence of the prolonged retention, rather than increased synthesis. Thus the
      absence of one of the TPs did not significantly affect transcription or
      translation of the other basic proteins, but it did affect posttranslational
      events.

PMID- 15163615
TI  - Estrogen metabolism in the equine conceptus and endometrium during early
      pregnancy in relation to estrogen concentrations in yolk-sac fluid.
AB  - Because estradiol (E(2)) production by the early equine conceptus is considered
      crucial to the establishment of pregnancy, the amounts of E(2), estrone (E(1)),
      and their sulfates (E(2)S, E(1)S) were measured by RIA in yolk-sac fluid of 63
      conceptuses collected by transcervical lavage over the period of 11-26 days after
      ovulation. Amounts increased significantly with age of conceptus, especially for
      E(1)S. Then, the metabolism of E(2), which may be highly relevant for its action,
      was examined in the conceptus and endometrium over the period when the conceptus
      ceases to migrate within the uterus. Eleven conceptuses collected mainly on Days
      12, 15, and 18, with endometrial biopsy samples taken immediately thereafter,
      were used for steroid metabolic studies. Trophoblastic and endometrial tissues
      were incubated with [(3)H]-labeled E(2) or E(1), and with [(14)C]-E(1) in one
      experiment. Steroids were recovered from the media by solid-phase extraction
      (SPE) and eluted separately as unconjugated and conjugated fractions. Conjugation
      increased from Day 12 for the trophoblast (more so by bilaminar than trilaminar
      tissues on Day 18) and was much greater for endometrium, with almost all as
      sulfoconjugates. HPLC profiles of free and sulfate fractions were obtained from a
      gradient of acetonitrile/water. Interconversion (E(2) right harpoon over left
      harpoon E(1)) by trophoblast varied with development; it favored E(2) in older
      conceptuses, more in bilaminar than trilaminar tissues. Some more polar products
      were also noted, with loss of tritium seen as [(3)H](2)O at SPE, and confirmed by
      HPLC in a second system with authentic reference steroids. Almost all
      radioactivity in the endometrium was present as E(2) in both free and sulfate
      fractions. It was concluded that local metabolism of E(2) is quantitatively
      significant and may play an important role in the actions of the large amounts of
      estradiol produced by the early equine conceptus.

PMID- 15163614
TI  - Oxygen-regulated gene expression in bovine blastocysts.
AB  - Oxygen concentrations used during in vitro embryo culture can influence embryo
      development, cell numbers, and gene expression. Here we propose that the
      preimplantation bovine embryo possesses a molecular mechanism for the detection
      of, and response to, oxygen, mediated by a family of basic helix-loop-helix
      transcription factors, the hypoxia-inducible factors (HIFs). Day 5 compacting
      bovine embryos were cultured under different oxygen tensions (2%, 7%, 20%) and
      the effect on the expression of oxygen-regulated genes, development, and cell
      number allocation and HIFalpha protein localization were examined. Bovine in
      vitro-produced embryos responded to variations in oxygen concentration by
      altering gene expression. GLUT1 expression was higher following 2% oxygen culture
      compared with 7% and 20% cultured blastocysts. HIF mRNA expression (HIF1alpha,
      HIF2alpha) was unaltered by oxygen concentration. HIF2alpha protein was
      predominantly localized to the nucleus of blastocysts. In contrast, HIF1alpha
      protein was undetectable at any oxygen concentration or in the presence of the
      HIF protein stabilizer desferrioxamine (DFO), despite being detectable in cumulus
      cells following normal maturation conditions, acute anoxic culture, or in the
      presence of DFO. Oxygen concentration also significantly altered inner cell mass
      cell proportions at the blastocyst stage. These results suggest that oxygen can
      influence gene expression in the bovine embryo during postcompaction development
      and that these effects may be mediated by HIF2alpha.

PMID- 15163616
TI  - Temporal changes occur in the neuroendocrine control of gonadotropin secretion in
      aging female rats: role of progesterone.
AB  - The present study examined the gonadotropin surge-inducing actions of estradiol
      (E(2)), both alone and with progesterone (P(4)), in middle-aged, early persistent
      estrous (PE) female rats that had become PE within 35 days. In addition, we also
      assessed the effect of P(4) on the mating-induced gonadotropin surges in these
      acyclic animals. Early PE rats were ovariectomized and received E(2) implants
      (Day 0). On Day 4, an s.c. injection of P(4) (0.5 mg/ 100 g body weight) at 1200
      h markedly increased plasma P(4) and elicited both LH and FSH surges, whereas
      vehicle-treated controls displayed no rise in P(4) or gonadotropins. This
      observation confirms that at middle age, female rats no longer respond to the
      positive-feedback stimulation of E(2) on gonadotropin surges whenever the estrous
      cyclicity ceases. As PE continued, such a surge-inducing action of E(2) plus P(4)
      became diminished after 75 days of PE and disappeared thereafter. When caged with
      males, vehicle-treated early PE rats display a mating-induced increase in P(4)
      from the adrenal along with small gonadotropin surges. The amplitude of these
      mating-induced gonadotropin surges was enhanced by supplementation with exogenous
      P(4) in early PE rats. Our findings indicate that during the early phase of PE,
      the surge-inducing action of E(2) and P(4) remains intact but deteriorates as PE
      continues. Thus, a deficiency in P(4) secretion during aging may contribute to
      the diminished gonadotropin surge response in the hypothalamic-pituitary axis and
      the subsequent cessation of estrous cyclicity.

PMID- 15163617
TI  - Compartmentalization of prion isoforms within the reproductive tract of the ram.
AB  - Cellular prion protein (Prp(C)) is a glycoprotein usually associated with
      membranes via its glycosylphosphatidylinositol (GPI) anchor. The trans
      conformational form of this protein (Prp(SC)) is the suggested agent responsible
      for transmissible neurodegenerative spongiform encephalopathies. This protein has
      been shown on sperm and in the reproductive fluids of males. Antibodies directed
      against the C-terminal sequence near the GPI-anchor site, an N-terminal sequence,
      and against the whole protein showed that the Prp isoforms were compartmentalized
      within the reproductive tract of the ram. Immunoblotting with the three
      antibodies showed that the complete protein and both N- and C-terminally
      truncated and glycosylated isoforms are present within cauda epididymal fluid and
      seminal plasma. Moreover, we demonstrate that in these fluids, the Prp(C)
      isoforms are both in a soluble state as well as associated with small membranous
      vesicles (epididymosomes). We also report that only one major glycosylated 25 kDa
      C-terminally truncated Prp(C) isoform is associated with sperm from the testis,
      cauda epididymis, and semen, and this form is also present in the sperm
      cytoplasmic droplets that are released during maturation. In sperm, this C
      terminal truncated form was found to be associated with membrane lipid rafts
      present in the mature sperm, suggesting a role for it in the terminal stages of
      sperm maturation.

PMID- 15163618
TI  - Short day lengths delay reproductive aging.
AB  - Caloric restriction and hormone treatment delay reproductive senescence in female
      mammals, but a natural model of decelerated reproductive aging does not presently
      exist. In addition to describing such a model, this study shows that an abiotic
      signal (photoperiod) can induce physiological changes that slow senescence.
      Relative to animals born in April, rodents born in September delay their first
      reproductive effort by up to 7 mo, at which age reduced fertility is expected. We
      tested the hypothesis that the shorter day lengths experienced by late-born
      Siberian hamsters ameliorate the reproductive decline associated with advancing
      age. Short-day females (10L:14D) achieved puberty at a much later age than long
      day animals (14L:10D) and had twice as many ovarian primordial follicles. At 10
      mo of age, 86% of females previously maintained in short day lengths produced
      litters, compared with 58% of their long day counterparts. Changes in pineal
      gland production of melatonin appear to mediate the effects of day length on
      reproductive aging; only 30% of pinealectomized females housed in short days
      produced litters. Exposure to short days induces substantial decreases in
      voluntary food intake and body mass, reduced ovarian estradiol secretion, and
      enhanced production of melatonin. One or more of these changes may account for
      the protective effect of short day lengths on female reproduction. In delaying
      reproductive senescence, the decrease in day length after the summer solstice is
      of presumed adaptive significance for offspring born late in the breeding season
      that first breed at an advanced chronological age.

PMID- 15163619
TI  - Hydroxyl radical activation of a Ca(2+)-sensitive nonselective cation channel
      involved in epithelial cell necrosis.
AB  - In a previous work the involvement of a fenamate-sensitive Ca(2+)-activated
      nonselective cation channel (NSCC) in free radical-induced rat liver cell
      necrosis was demonstrated (5). Therefore, we studied the effect of radical oxygen
      species and oxidizing agents on the gating behavior of a NSCC in a liver-derived
      epithelial cell line (HTC). Single-channel currents were recorded in HTC cells by
      the excised inside-out configuration of the patch-clamp technique. In this cell
      line, we characterize a 19-pS Ca(2+)-activated, ATP- and fenamate-sensitive NSCC
      nearly equally permeable to monovalent cations. In the presence of Fe(2+),
      exposure of the intracellular side of NSCC to H(2)O(2) increased their open
      probability (P(o)) by approximately 40% without affecting the unitary
      conductance. Desferrioxamine as well as the hydroxyl radical (.OH) scavenger MCI
      186 inhibited the effect of H(2)O(2), indicating that the increase in P(o) was
      mediated by.OH. Exposure of the patch membrane to the oxidizing agent 5,5'-dithio
      bis-2-nitrobenzoic acid (DTNB) had a similar effect to.OH. The increase in P(o)
      induced by.OH or DTNB was not reverted by preventing formation or by DTNB
      washout, respectively. However, the reducing agent dithiothreitol completely
      reversed the effects on P(o) of both.OH and DTNB. A similar increase in P(o) was
      observed by applying the physiological oxidizing molecule GSSG. Moreover, GSSG
      oxidized channels showed enhanced sensitivity to Ca(2+). The effect of GSSG was
      fully reversed by GSH. These results suggest an intracellular site(s) of action
      of oxidizing agents on cysteine targets on the fenamate-sensitive NSCC protein
      implicated in epithelial cell necrosis.

PMID- 15163620
TI  - CREB trans-activates the murine H(+)-K(+)-ATPase alpha(2)-subunit gene.
AB  - Despite its key role in potassium homeostasis, transcriptional control of the
      H(+)-K(+)-ATPase alpha(2)-subunit (HKalpha(2)) gene in the collecting duct
      remains poorly characterized. cAMP increases H(+)-K(+)-ATPase activity in the
      collecting duct, but its role in activating HKalpha(2) transcription has not been
      explored. Previously, we demonstrated that the proximal 177 bp of the HKalpha(2)
      promoter confers basal collecting duct-selective expression. This region contains
      several potential cAMP/Ca(2+)-responsive elements (CRE). Accordingly, we examined
      the participation of CRE-binding protein (CREB) in HKalpha(2) transcriptional
      control in murine inner medullary collecting duct (mIMCD)-3 cells. Forskolin and
      vasopressin induced HKalpha(2) mRNA levels, and CREB overexpression stimulated
      the activity of HKalpha(2) promoter-luciferase constructs. Serial deletion
      analysis revealed that CREB inducibility was retained in a construct containing
      the proximal 100 bp of the HKalpha(2) promoter. In contrast, expression of a
      dominant negative inhibitor (A-CREB) resulted in 60% lower HKalpha(2) promoter
      luciferase activity, suggesting that constitutive CREB participates in basal
      HKalpha(2) transcriptional activity. A constitutively active CREB mutant (CREB
      VP16) strongly induced HKalpha(2) promoter-luciferase activity, whereas
      overexpression of CREBdLZ-VP16, which lacks the CREB DNA-binding domain,
      abolished this activation. In vitro DNase I footprinting and gel shift/supershift
      analysis of the proximal promoter with recombinant glutathione S-transferase
      (GST)-CREB-1 and mIMCD-3 cell nuclear extracts revealed sequence-specific DNA
      CREB-1 complexes at -86/-60. Mutation at three CRE-like sequences within this
      region abolished CREB-1 DNA-binding activity and abrogated CREB-VP16 trans
      activation of the HKalpha(2) promoter. In contrast, mutation of the neighboring 
      104/-94 kappabeta element did not alter CREB-VP16 trans-activation of the
      HKalpha(2) promoter. Thus CREB-1, binding to one or more CRE-like elements in the
      -86/-60 region, trans-activates the HKalpha(2) gene and may represent an
      important link between rapid and delayed effects of cAMP on HKalpha(2) activity.

PMID- 15163621
TI  - Imaging endoplasmic reticulum calcium with a fluorescent biosensor in transgenic
      mice.
AB  - The use of biosynthetic fluorescent sensors is an important new approach for
      imaging Ca(2+) in cells. Genetically encoded indicators based on green
      fluorescent protein, calmodulin, and fluorescence resonance energy transfer
      (FRET) have been utilized to measure Ca(2+) in nonmammalian transgenic organisms
      and provide information about the organization and regulation of Ca(2+) signaling
      events in vivo. However, expression of biosynthetic FRET-based Ca(2+) indicators
      in transgenic mammals has proven to be problematic. Here, we report transgenic
      expression of an endoplasmic reticulum (ER) Ca(2+) biosensor in mouse pancreas.
      We targeted expression of a yellow cameleon3.3er (YC3.3er) transgene with mouse
      insulin I promoter. YC3.3er protein expression was limited to pancreatic beta
      cells within islets of Langerhans and absent in the exocrine pancreas and other
      tissues. Animals developed and matured normally; sensor expression was unaffected
      by age. Glucose tolerance in transgenic mice was also unaffected, indicating the
      transgenic biosensor did not impair endocrine pancreas function. ER Ca(2+)
      responses after administration of thapsigargin, carbachol, and glucose were
      measured in individual beta-cells of intact islets using confocal microscopy and
      confirmed the function of the biosensor. We conclude that controlling transgene
      transcription with a cell-specific promoter permits transgenic expression of FRET
      based Ca(2+) sensors in mammals and that this approach will facilitate real-time
      optical imaging of signal transduction events in living tissues.

PMID- 15163622
TI  - A key angiogenic role of monocyte chemoattractant protein-1 in
      hemangioendothelioma proliferation.
AB  - Angiomatous lesions are common in infants and children. Hemangioendotheliomas
      (HE) represent one type of these lesions. Endothelial cell proliferation and the
      development of vascular/blood cell-filled spaces are inherent in the growth of
      HE. Therefore, understanding mechanisms that regulate the proliferation of these
      lesions should provide key insight into mechanisms regulating angiogenesis. A
      murine model was used to test the significance of monocyte chemoattractant
      protein (MCP)-1 in HE proliferation. EOMA cells, a cell line derived from a
      spontaneously arising murine HE, generate these lesions with 100% efficiency when
      injected subcutaneously into syngeneic mice. MCP-1 produced by EOMA cells recruit
      macrophages, which were shown to induce angiogenic behavior in EOMA cells by
      stimulating transwell migration and inducing sprout formation on type I collagen
      gels. When EOMA cells were injected into MCP-1(-/-) mice, only 50% of the mice
      developed tumors, presumably because the low levels of MCP-1 expressed by the
      injected EOMA cells were enough to overcome any host deficits of this chemokine.
      When EOMA cells were coinjected with a neutralizing antibody to MCP-1, tumors
      failed to develop in any of the treated mice, including syngeneic 129P3, C57Bl/6
      (wild type), and MCP-1(-/-). These results present the first evidence that MCP-1
      is required for HE proliferation and may promote the growth of these lesions by
      stimulating angiogenic behavior of endothelial cells. This study has produced the
      first in vivo evidence of a complete response for any neoplasm, specifically a
      vascular proliferative lesion, to anti-MCP-1 therapy in animals with intact
      immune systems.

PMID- 15163623
TI  - Regional rheological differences in locomoting neutrophils.
AB  - Intracellular rheology is a useful probe of the mechanisms underlying spontaneous
      or chemotactic locomotion and transcellular migration of leukocytes. We
      characterized regional rheological differences between the leading, body, and
      trailing regions of isolated, adherent, and spontaneously locomoting human
      neutrophils. We optically trapped intracellular granules and measured their
      displacement for 500 ms after a 100-nm step change in the trap position. Results
      were analyzed in terms of simple viscoelasticity and with the use of structural
      damping (stress relaxation follows a power law in time). Structural damping fit
      the data better than did viscoelasticity. Regional viscoelastic stiffness and
      viscosity or structural damping storage and loss moduli were all significantly
      lower in leading regions than in pooled body and/or trailing regions (the latter
      were not significantly different). Structural damping showed similar levels of
      elastic and dissipative stresses in body and/or trailing regions; leading regions
      were significantly more fluidlike (increased power law exponent). Cytoskeletal
      disruption with cytochalasin D or nocodazole made body and/or trailing regions
      approximately 50% less elastic and less viscous. Cytochalasin D completely
      suppressed pseudopodial formation and locomotion; nocodazole had no effect on
      leading regions. Neither drug changed the dissipation-storage energy ratio. These
      results differ from those of studies of neutrophils and other cell types probed
      at the cell membrane via beta(2)-integrin receptors, which suggests a distinct
      role for the cell cortex or focal adhesion complexes. We conclude that 1)
      structural damping well describes intracellular rheology, and 2) while not
      conclusive, the significantly more fluidlike behavior of the leading edge
      supports the idea that intracellular pressure may be the origin of motive force
      in neutrophil locomotion.

PMID- 15163624
TI  - Signal transduction of betacellulin in growth and migration of vascular smooth
      muscle cells.
AB  - Epidermal growth factor (EGF) family ligands have been implicated in
      cardiovascular diseases because of their enhanced expression in vascular lesions
      and their promoting effects on growth and migration of vascular smooth muscle
      cells (VSMCs). Betacellulin (BTC), a novel EGF family ligand, has been shown to
      be expressed in atherosclerotic lesions and to be a potent growth factor of
      VSMCs. However, the molecular mechanisms downstream of BTC involved in mediating
      vascular remodeling remain largely unknown. Therefore, the aim of this study was
      to examine the effects of BTC on signal transduction, growth, and migration in
      VSMCs. We found that BTC stimulated phosphorylation of EGF receptor (EGFR) at
      Tyr1068, which was completely blocked by an EGFR kinase inhibitor, AG-1478. BTC
      also phosphorylated ErbB2 at Tyr877, Tyr1112, and Tyr1248 and induced association
      of ErbB2 with EGFR, suggesting their heterodimerization in VSMCs. In postreceptor
      signal transduction, BTC stimulated phosphorylation of extracellular signal
      regulated kinase (ERK)1/2, Akt, and p38 mitogen-activated protein kinase (MAPK).
      Moreover, BTC stimulated proliferation and migration of VSMCs. ERK and Akt
      inhibitors suppressed migration markedly and proliferation partially, whereas the
      p38 inhibitor suppressed migration partially but not proliferation. In addition,
      we found the presence of endogenous BTC in conditioned medium of VSMCs and an
      increase of BTC on angiotensin II stimulation. In summary, BTC promotes growth
      and migration of VSMCs through activation of EGFR, ErbB2, and downstream
      serine/threonine kinases. Together with the expression and processing of
      endogenous BTC in VSMCs, our results suggest a critical involvement of BTC in
      vascular remodeling.

PMID- 15163625
TI  - A major flagellum sialoglycoprotein in sea urchin sperm contains a novel
      polysialic acid, an alpha2,9-linked poly-N-acetylneuraminic acid chain, capped by
      an 8-O-sulfated sialic acid residue.
AB  - A new type of polysialic acid (polySia) structure was demonstrated to occur in a
      major unknown sialoglycoprotein with a diverse molecular mass of 40-80 kDa in sea
      urchin sperm. The polySia-containing glycan structure was determined to be HSO(3)
      ->8Neu5Acalpha2-->9(Neu5Acalpha2-->9)(n-2) Neu5Acalpha2-->6GalNAcalpha1-->Ser/Thr
      (n, on average 15), based on carbohydrate analysis of the sialoglycopeptide
      obtained by an exhaustive protease digestion of whole sperm, fluorometric anion
      exchange high-performance liquid chromatography, and methylation analysis. The
      sulfate group was predominantly localized to the nonreducing terminus of the
      polySia chain. This is the first example of an alpha2,9-linked polySia structure
      in animal sperm. The polySia-containing sialoglycoprotein was present in sperm
      flagellum but not in the head. Furthermore, this sialoglycoprotein localized in
      the sperm lipid raft, which contains an enriched ganglioside (Neu5Acalpha2-
      >8Neu5Acalpha2-->6GlcCer), a receptor for sperm-activating peptide (speract), and
      its associated guanylate cyclase.

PMID- 15163626
TI  - Effects of galectin-1 on regulation of progesterone production in granulosa cells
      from pig ovaries in vitro.
AB  - The detection of galectin-1 (gal-1) in pig granulosa cell lysates by
      immunoblotting and its cytosolic as well as membrane-associated localization
      prompted us to study its effects on cell proliferation and regulation of
      progesterone synthesis. The lectin stimulated the proliferation of granulosa
      cells from pig ovaries cultured in serum-free medium. Gal-1 inhibited the FSH
      stimulated progesterone synthesis of granulosa cells. This inhibitory effect was
      strongly reduced by the disaccharidic competitor lactose at 30 mM. The absence of
      inhibitory effects on dibutyryl-cAMP (db-cAMP), forskolin, and pregnenolone
      enhanced cellular progesterone synthesis suggests that gal-1interferes with the
      receptor-dependent mechanism of FSH-stimulated progesterone production. In FSH
      stimulated granulosa cells, western blot analysis revealed the gal-1-mediated
      suppression of the cytochrome P450-dependent cholesterol side chain cleavage
      enzyme (P450(SCC)) that catalyzes the conversion of cholesterol to pregnenolone.
      In the presence of 30 mM lactose, the gal-1-reduced P450(SCC) expression was
      prevented. Strongly reduced mRNA levels were recorded for P450(SCC) and 3beta
      hydroxysteroid dehydrogenase/isomerase (3beta-HSD) when FSH-stimulated granulosa
      cells were cultured in the presence of gal-1. We conclude that gal-1 exerts its
      inhibitory effect on steroidogenic activity of granulosa cells by interfering the
      hormone-receptor interaction resulting in decreased responses to FSH stimulation.

PMID- 15163627
TI  - Development of the mammary gland requires DGAT1 expression in stromal and
      epithelial tissues.
AB  - Mammary gland development is a complex process that is dependent on interactions
      between the developing mammary epithelium and the surrounding stromal tissues. We
      show that mice lacking the triglyceride synthesis enzyme acyl CoA:diacylglycerol
      transferase 1 (DGAT1) have impaired mammary gland development, characterized by
      decreased epithelial proliferation and alveolar development, and reduced
      expression of markers of functional differentiation. Transplantation studies
      demonstrate that the impaired development results from a deficiency of DGAT1 in
      both the stromal and epithelial tissues. Our findings are the first to link
      defects in stromal lipid metabolism to impaired mammary gland development.

PMID- 15163628
TI  - Xenopus Staufen is a component of a ribonucleoprotein complex containing Vg1 RNA
      and kinesin.
AB  - RNA localization is a key mechanism for generating cell and developmental
      polarity in a wide variety of organisms. We have performed studies to investigate
      a role for the Xenopus homolog of the double-stranded RNA-binding protein,
      Staufen, in RNA localization during oogenesis. We have found that Xenopus Staufen
      (XStau) is present in a ribonucleoprotein complex, and associates with both a
      kinesin motor protein and vegetally localized RNAs Vg1 and VegT. A functional
      role for XStau was revealed through expression of a dominant-negative version
      that blocks localization of Vg1 RNA in vivo. Our results suggest a central role
      for XStau in RNA localization in Xenopus oocytes, and provide evidence that
      Staufen is a conserved link between specific mRNAs and the RNA localization
      machinery.

PMID- 15163629
TI  - Sox17 and beta-catenin cooperate to regulate the transcription of endodermal
      genes.
AB  - Recent studies have led to a model of the molecular pathway that specifies the
      endoderm during vertebrate gastrulation. The HMG box transcription factor Sox17
      is a key component of this pathway and is essential for endoderm formation;
      however, the molecular events controlled by Sox17 are largely unknown. We have
      identified several direct transcriptional targets of Sox17, including Foxa1 and
      Foxa2. We show that beta-catenin, a component of Wnt signaling pathway,
      physically interacts with Sox17 and potentiates its transcriptional activation of
      target genes. We identify a motif in the C terminus of Sox17, which is conserved
      in all the SoxF subfamily of Sox proteins, and this motif is required for the
      ability of Sox17 to both transactivate target genes and bind beta-catenin.
      Nuclear beta-catenin is present in endoderm cells of the gastrula, and depletion
      of beta-catenin from embryos results in a repression of Sox17 target genes. These
      data suggest that in a mechanism analogous to Tcf/Lef interacting with beta
      catenin, Sox17 and beta-catenin interact to transcribe endodermal target genes.

PMID- 15163630
TI  - Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an
      absolute requirement for mitochondrial ATP production.
AB  - At fertilisation, repetitive increases in the intracellular Ca2+ concentration,
      [Ca2+]i, drive the completion of meiosis and initiate the development of the
      quiescent egg into an embryo. Although the requirement for an ATP supply is
      evident, the relative roles of potential ATP sources remains unclear in the
      mammalian egg, and the specific role of mitochondria in [Ca2+]i regulation as
      well as in the sperm-triggered [Ca2+] oscillations is unknown. We have used
      fluorescence and luminescence imaging to investigate mitochondrial activity in
      single mouse eggs. Simultaneous imaging of mitochondrial redox state (NADH and
      flavoprotein autofluorescence) and [Ca2+]i revealed that sperm-triggered [Ca2+]
      oscillations are transmitted to the mitochondria where they directly stimulate
      mitochondrial activity. Inhibition of mitochondrial oxidative phosphorylation
      caused release of Ca2+ from the endoplasmic reticulum because of local ATP
      depletion. Mitochondrial ATP production is an absolute requirement for
      maintaining a low resting [Ca2+]i and for sustaining sperm-triggered [Ca2+]
      oscillations. Luminescence measurements of intracellular [ATP] from single eggs
      confirmed that mitochondrial oxidative phosphorylation is the major source of ATP
      synthesis in the dormant unfertilised egg. These observations show that a high
      local ATP consumption is balanced by mitochondrial ATP production, and that
      balance is critically poised. Mitochondrial ATP supply and demand are thus
      closely coupled in mouse eggs. As mitochondrial ATP generation is essential to
      sustain the [Ca2+] signals that are crucial to initiate development,
      mitochondrial integrity is clearly fundamental in sustaining fertility in
      mammalian eggs.

PMID- 15163631
TI  - Presenilin 1 in migration and morphogenesis in the central nervous system.
AB  - Morphogenesis of the central nervous system relies in large part upon the correct
      migration of neuronal cells from birthplace to final position. Two general modes
      of migration govern CNS morphogenesis: radial, which is mostly glia-guided and
      topologically relatively simple; and tangential, which often involves complex
      movement of neurons in more than one direction. We describe the consequences of
      loss of function of presenilin 1 on these fundamental processes. Previous studies
      of the central nervous system in presenilin 1 homozygote mutant embryos
      identified a premature neuronal differentiation that is transient and localized,
      with cortical dysplasia at later stages. We document widespread effects on CNS
      morphogenesis that appear strongly linked to defective neuronal migration. Loss
      of presenilin 1 function perturbs both radial and tangential migration in
      cerebral cortex, and several tangential migratory pathways in the brainstem. The
      inability of cells to execute their migratory trajectories affects cortical
      lamination, formation of the facial branchiomotor nucleus, the spread of
      cerebellar granule cell precursors to form the external granule layer and
      development of the pontine nuclei. Finally, overall morphogenesis of the mid
      hindbrain region is abnormal, resulting in incomplete midline fusion of the
      cerebellum and overgrowth of the caudal midbrain. These observations indicate
      that in the absence of presenilin 1 function, the ability of a cell to move can
      be severely impaired regardless of its mode of migration, and, at a grosser
      level, brain morphogenesis is perturbed. Our results demonstrate that presenilin
      1 plays a much more important role in brain development than has been assumed,
      consistent with a pleiotropic involvement of this molecule in cellular signaling.

PMID- 15163632
TI  - Expression profiling of the developing and mature Nrl-/- mouse retina:
      identification of retinal disease candidates and transcriptional regulatory
      targets of Nrl.
AB  - The rod photoreceptor-specific neural retina leucine zipper protein Nrl is
      essential for rod differentiation and plays a critical role in regulating gene
      expression. In the mouse retina, rods account for 97% of the photoreceptors;
      however, in the absence of Nrl (Nrl-/-), no rods are present and a concomitant
      increase in cones is observed. A functional all-cone mouse retina represents a
      unique opportunity to investigate, at the molecular level, differences between
      the two photoreceptor subtypes. Using mouse GeneChips (Affymetrix), we have
      generated expression profiles of the wild-type and Nrl-/- retina at three time
      points representing distinct stages of photoreceptor differentiation. Comparative
      data analysis revealed 161 differentially expressed genes; of which, 78 exhibited
      significantly lower and 83 higher expression in the Nrl-/- retina. Hierarchical
      clustering was utilized to predict the function of these genes in a temporal
      context. The differentially expressed genes primarily encode proteins associated
      with signal transduction, transcriptional regulation, intracellular transport and
      other processes, which likely correspond to differences between rods and cones
      and/or retinal remodeling in the absence of rods. A significant number of these
      genes may serve as candidates for diseases involving rod or cone dysfunction.
      Chromatin immunoprecipitation assay showed that in addition to the rod
      phototransduction genes, Nrl might modulate the promoters of many functionally
      diverse genes in vivo. Our studies provide molecular insights into differences
      between rod and cone function, yield interesting candidates for retinal diseases
      and assist in identifying transcriptional regulatory targets of Nrl.

PMID- 15163633
TI  - Six5 is required for spermatogenic cell survival and spermiogenesis.
AB  - Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine
      defects that include testicular and tubular atrophy, oligospermia, Leydig cell
      hyperproliferation and increased follicle stimulating hormone (FSH) levels. DM1
      results from a CTG expansion that causes transcriptional silencing of the
      flanking SIX5 allele. Loss of Six5 results in male sterility and a progressive
      decrease in testicular mass with age. We demonstrate a strict requirement of Six5
      for both spermatogenic cell survival and spermiogenesis. Leydig cell
      hyperproliferation and increased intra-testicular testosterone levels are
      observed in the Six5-/- mice. Although increased FSH levels are observed in the
      Six5+/- and Six5-/- mice, serum testosterone levels and intra-testicular inhibin
      alpha and inhibin beta B levels are not altered in the Six5 mutant animals when
      compared with controls. Significantly, steady-state c-Kit levels are reduced in
      the Six5-/- testis. Thus, decreased c-Kit levels could contribute to the elevated
      spermatogenic cell apoptosis and Leydig cell hyperproliferation in the Six5-/-
      mice. The results support the hypothesis that the reduced SIX5 levels contribute
      to the male reproductive defects in DM1.

PMID- 15163634
TI  - Mutant huntingtin directly increases susceptibility of mitochondria to the
      calcium-induced permeability transition and cytochrome c release.
AB  - Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine
      stretch in the huntingtin protein, conferring a novel property on the protein
      that leads to the loss of striatal neurons. Defects in mitochondrial function
      have been implicated in the pathogenesis of HD. Here, we have examined the
      hypothesis that the mutant huntingtin protein may directly interact with the
      mitochondrion and affect its function. In human neuroblastoma cells and clonal
      striatal cells established from HdhQ7 (wild-type) and HdhQ111 (mutant) homozygote
      mouse knock-in embryos, huntingtin was present in a purified mitochondrial
      fraction. Subfractionation of the mitochondria and limited trypsin digestion of
      the organelle demonstrated that huntingtin was associated with the outer
      mitochondrial membrane. We further demonstrated that a recombinant truncated
      mutant huntingtin protein, but not a wild-type, directly induced mitochondrial
      permeability transition (MPT) pore opening in isolated mouse liver mitochondria,
      an effect that was prevented completely by cyclosporin A (CSA) and ATP.
      Importantly, the mutant huntingtin protein significantly decreased the Ca2+
      threshold necessary to trigger MPT pore opening. We found a similar increased
      susceptibility to the calcium-induced MPT in liver mitochondria isolated from a
      knock-in HD mouse model. The mutant huntingtin protein-induced MPT pore opening
      was accompanied by a significant release of cytochrome c, an effect completely
      inhibited by CSA. These findings suggest that the development of specific MPT
      inhibitors may be an interesting therapeutic avenue to delay the onset of HD.

PMID- 15163635
TI  - The subcellular localization of the ChoRE-binding protein, encoded by the
      Williams-Beuren syndrome critical region gene 14, is regulated by 14-3-3.
AB  - The Williams-Beuren syndrome (WBS) is a contiguous gene syndrome caused by
      chromosomal rearrangements at chromosome band 7q11.23. Several endocrine
      phenotypes, in particular impaired glucose tolerance and silent diabetes, have
      been described for this clinically complex disorder. The WBSCR14 gene, one of the
      genes mapping to the WBS critical region, encodes a member of the basic-helix
      loop-helix leucine zipper family of transcription factors, which dimerizes with
      the Max-like protein, Mlx. This heterodimeric complex binds and activates, in a
      glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the
      promoter of lipogenic enzymes. We identified five novel WBSCR14-interacting
      proteins, four 14-3-3 isotypes and NIF3L1, which form a single polypeptide
      complex in mammalian cells. Phosphatase treatment abrogates the association
      between WBSCR14 and 14-3-3, as shown previously for multiple 14-3-3 interactors.
      WBSCR14 is exported actively from the nucleus through a CRM1-dependent mechanism.
      This translocation is contingent upon the ability to bind 14-3-3. Through this
      mechanism the 14-3-3 isotypes directly affect the WBSCR14:Mlx complexes, which
      activate the transcription of lipogenic genes.

PMID- 15163636
TI  - Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW,
      but not MYC in MYC-containing double minutes in myeloid malignancies.
AB  - Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are
      found in approximately 1% of karyotypically abnormal acute myeloid leukemias
      (AML) and myelodysplastic syndromes (MDS). The MYC gene at 8q24 has been reported
      to be amplified in the majority of the cases, and generally it has been assumed
      that MYC is the target gene. However, only a few studies have focused on the
      extent of the amplicon or on the expression patterns of the amplified genes. We
      have studied six cases (five AML and one MDS) with MYC-containing dmin. Detailed
      fluorescence in situ hybridization analyses identified a common 4.3 Mb amplicon,
      with clustered proximal and distal breakpoints, harboring eight known genes
      (C8FW, NSE2, POU5FLC20, MYC, PVT1, AK093424, MGC27434 and MLZE). The
      corresponding region was deleted in one of the chromosome 8 homologues in five of
      the six cases, suggesting that the dmin originated through extra replication (or
      loop-formation)--excision--amplification. Northern blot analysis revealed that
      MYC was not overexpressed. Instead, the C8FW gene, encoding a phosphoprotein
      regulated by mitogenic pathways, displayed increased expression. These results
      exclude MYC as the target gene and indicate that overexpression of C8FW may be
      the functionally important consequence of 8q24 amplicons in AML and MDS.

PMID- 15163637
TI  - SIAH1 targets the alternative splicing factor T-STAR for degradation by the
      proteasome.
AB  - T-STAR is one of three members of the SAM68 family of RNA-binding proteins that
      have been shown to be involved in various gene expression pathways including the
      control of pre-mRNA splicing. We employed a two-hybrid screen to identify
      proteins that interact with human T-STAR. The predominant interacting proteins
      were the E3 ubiquitin ligases SIAH1 and SIAH2. We found that SIAH1 bound to an
      octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation.
      Rodent T-STAR orthologues (also known as etoile or SLM2) were not targeted for
      degradation by SIAH1. However a double amino acid substitution of mouse T-STAR
      that mimics the human SIAH1-binding site brought mouse T-STAR under in vivo
      control of SIAH1. Using a minigene transfection assay for alternative splicing
      activity we showed that human T-STAR, like its rodent orthologues can influence
      splice site choice and that human, but not mouse, T-STAR-dependent alternative
      splicing is modulated by SIAH1. Western blots of protein from purified germ cells
      indicated that SIAH1 protein expression peaks in meiosis. In mouse, T-STAR is co
      expressed with SIAH1 during meiosis but, in humans, T-STAR is only strongly
      expressed after meiosis. Comparative sequence analysis showed SIAH-mediated
      proteasomal degradation of T-STAR has evolved in the primate lineage.
      Collectively these data suggest that SIAH-mediated down regulation of alternative
      splicing may be an important developmental difference between otherwise highly
      conserved T-STAR proteins.

PMID- 15163638
TI  - Stem cell based therapeutical approach of male infertility by teratocarcinoma
      derived germ cells.
AB  - Infertility affects 13-18% of couples and growing evidence from clinical and
      epidemiological studies suggests an increasing incidence of male reproductive
      problems. There is a male factor involved in up to half of all infertile couples.
      The pathogenesis of male infertility can be reflected by defective
      spermatogenesis due to failure in germ cell proliferation and differentiation. We
      report here in vitro generation of a germ cell line (SSC1) from the pluripotent
      teratocarcinoma cells by a novel promoter-based sequential selection strategy and
      show that the SSC1 cell line form mature seminiferous tubule structures, and
      support spermatogenesis after transplantation into recipient testes. To select
      differentiated germ cell population, we generated a fusion construct (Stra8-EGFP)
      harbouring the 1.4 kb promoter region of germ line specific gene Stra8 and coding
      region of enhanced green fluorescence protein. This region was sufficient to
      direct gene expression to the germinal stem cells in testis of transgenic mice.
      The purified cells expressed the known molecular markers of spermatogonia Rbm,
      cyclin A2, Tex18, Stra8 and Dazl and the beta1- and alpha6-integrins
      characteristic of the stem cell fraction. This cell line undergoes meiosis and
      can develop into sperm when transplanted into germ cell depleted testicular
      tubules. Sperm were viable and functional, as shown by fertilization after intra
      cytoplasmic injection into mouse oocytes. This approach provides the basis that
      is essential for studying the development and differentiation of male germ line
      stem cell, as well as for developing new approaches to reproductive engineering
      and infertility treatment.

PMID- 15163639
TI  - Agreement between husband and wife reports of domestic violence: evidence from
      poor refugee communities in Lebanon.
AB  - BACKGROUND: This paper compares husband and wife reports of wife beating using
      household survey data collected from poor Palestinian refugee communities in
      Lebanon. METHODS: The analyses are based on a matched data file of 417 currently
      married couples, drawn from a unique multi-purpose living conditions sample
      survey of about 3600 Palestinian refugee households interviewed in the spring and
      summer of 1999. Four outcomes (ever beaten, last year beating, beating during
      pregnancy, and injuries caused by beating) were analysed using Kappa statistics
      and per cent agreement. Logistic regression was used to analyse discordant
      reporting of wife beating during the year preceding the survey. RESULTS: Husband
      and wives' reports of the four different outcomes are in 'good' agreement as
      judged by Kappa coefficients, ranging from 0.62 for 'beaten during pregnancy' to
      0.69 for 'injuries resulting from beating'. Prevalence estimates of domestic
      violence are also remarkably similar. However, findings from a multivariate
      logistic regression model on agreement regarding 'last year beating' show that
      only age of men was a significant predictor of agreement, controlling for
      education level, marital duration, region of residence, household size, health
      status, and consanguinity. CONCLUSIONS: Our findings show that men's self-reports
      of their violent behaviour against their wives are fairly congruent with those of
      their spouses, implying that the perpetrators, men, can be 'trusted' in providing
      basic information on 'beating histories' in epidemiological and demographic
      population-based investigations in contexts similar to ours. However, care should
      be taken in studies of young men's current beating behaviour using only their
      self-reports.

PMID- 15163641
TI  - What is a case-control study?

PMID- 15163640
TI  - Tubal sterilization and risk of ovarian, endometrial and cervical cancer. A
      Danish population-based follow-up study of more than 65 000 sterilized women.
AB  - BACKGROUND: On the basis of a population-based cohort, we assessed the cancer
      risk, focusing on gynaecological cancers and pre-malignant lesions, among women
      with a previous tubal sterilization. METHODS: Using the Danish Hospital Discharge
      Register we identified 65 232 women who had a tubal sterilization (1977-1993).
      The cohort was followed for cancer occurrence, and compared with the expected
      number based on the national cancer incidence rates. RESULTS: The overall risk of
      ovarian cancer was decreased (standardized incidence ratio [SIR] = 0.82; 95% CI:
      0.6, 1.0), and it was still decreased > or =10 years after the sterilization (SIR
      = 0.65; 95% CI: 0.4, 1.0). The rate of endometrial cancer was also decreased (SIR
      = 0.66; 95% CI: 0.5, 1.0), the risk continued being moderately reduced during
      follow-up, although it was not statistically significant. CONCLUSIONS: In this
      nationwide, population-based study we find that women with tubal sterilization
      have a decreased risk of subsequent development of ovarian cancer. As the
      protective effect is not decreasing with years of follow-up, our data do not
      support that 'screening' bias can explain the protective effect, but indicate
      that the sterilization itself may convey a reduction in risk. The same pattern is
      found for endometrial cancer, the association being less strong.

PMID- 15163642
TI  - Long-term pulmonary complications in combatants exposed to mustard gas: a
      historical cohort study.
AB  - BACKGROUND: Sulphur mustard (mustard gas), the most widely used chemical agent in
      the Iran-Iraq war, affects many organs including the skin, the gastrointestinal
      and respiratory tracts, and the central nervous system. The aim of this study was
      to assess the cumulative incidence rate and annual incidence rate of pulmonary
      complications, and the rate ratio of related factors. METHODS: In a retrospective
      cohort study of 1337 soldiers with a history of mustard gas exposure, factors
      such as age, smoking habit, number of exposure episodes, and the use of gas masks
      were determined, together with an assessment of their relationship to the
      occurrence of long-term pulmonary complications. All patients residing in the
      Tehran area were enrolled in the study. Data collection was based on the
      subjects' medical records and included clinical, spirometric, and in some cases
      histopathological findings. RESULTS: The cumulative incidence rate of pulmonary
      complications was 31.6%; the lowest annual incidence rate was noted during the
      first year of follow-up (0.75/1000), and the highest rate recorded in the seventh
      year (76.9/1000). Estimated relative risks (RR) for various age groups are as
      follows: 1.13 (95% CI: 0.88, 1.46) for those aged 21-25 years; 1.49 (95% CI:
      1.10, 2.01) for ages 26-30; 1.70 (95% CI: 1.20, 2.40) for ages 31-35; and 2.09
      (95% CI: 1.57, 2.77) for subjects aged >/=36. RR with regard to other factors
      were: more than one versus single exposure 0.69 (95% CI: 0.42, 1.12); smoking
      versus non-smoking 1.08 (95% CI: 0.80, 1.45), and unprotected exposure versus
      protective mask use 3.04 (95% CI: 2.20, 4.20). CONCLUSION: The estimated risk of
      pulmonary complications from war exposure to mustard gas increased with age and
      for soldiers who had not worn masks.

PMID- 15163643
TI  - Commentary: Does tubal sterilization reduce the risk of gynaecological cancers?

PMID- 15163644
TI  - Live birth with sperm cryopreserved for 21 years prior to cancer treatment: case
      report.
AB  - Advances in cancer treatment have led to significant improvements in the
      likelihood of reaching remission and long-term survival for men. Chemo- and
      radiotherapy-induced infertility are significant treatment side effects.
      Cryopreservation before the start of treatment enables sperm to be stored,
      thereby preserving the man's potential fertility. Here, we describe the
      successful use (with ICSI) of sperm cryopreserved prior to cancer treatment, for
      a total of 21 years. We believe this to be the longest period of sperm
      cryopreservation, resulting in a live birth, so far reported in the literature.

PMID- 15163645
TI  - A further note on the sex ratios of births conceived during wartime.

PMID- 15163647
TI  - Evolutionary mapping of the SHV beta-lactamase and evidence for two separate IS26
      dependent blaSHV mobilization events from the Klebsiella pneumoniae chromosome.
AB  - OBJECTIVES: To determine the most likely evolutionary pathway that has led to the
      development of extended-spectrum SHV derivatives, and to the mobilization of
      blaSHV. MATERIALS AND METHODS: Evolutionary mapping used a shortest-path analysis
      of aligned blaSHV variants, and other basic bioinformatic approaches, such as
      CLUSTAL W and Blast were employed. RESULTS: Two main branches of the blaSHV
      evolutionary tree were located; both are derived from variant blaSHV-1 alleles.
      Identical mutations, responsible for extended-spectrum SHV substrate profiles,
      have been selected independently in each branch. There is evidence for a pool of
      non-mobile blaSHV framework sequences. Analysis of the genome sequence of
      Klebsiella pneumoniae confirms the chromosomal origin of blaSHV, whose
      mobilization has occurred at least twice, once for each of the main evolutionary
      branches. Both these mobilization events have been catalysed by IS26. Evolution
      of blaSHV to give common extended-spectrum variants is most likely to have
      occurred following mobilization. CONCLUSIONS: These data shed new light on the
      evolution and mobilization of blaSHV, and these observations may be useful in
      predicting what might happen in future, both for blaSHV, and for other beta
      lactamase genes.

PMID- 15163648
TI  - Effect of a high-molecular-weight component of cranberry on constituents of
      dental biofilm.
AB  - BACKGROUND: Previous studies have shown that high molecular-weight non-dialysable
      material derived from cranberry juice (NDM) inhibits co-aggregation of a variety
      of oral bacteria. OBJECTIVES: In the present study, we examined the effect of NDM
      on several constituents of the dental biofilm, glucosyltransferase (GTF) and
      fructosyltransferase (FTF), as well as on the adhesion of Streptococcus sobrinus.
      RESULTS: The activity of immobilized and soluble GTF and FTF was inhibited by NDM
      (P > 0.05). NDM also inhibited adhesion of S. sobrinus to hydroxyapatite (P <
      0.05). CONCLUSIONS: Our results indicate that NDM may affect biofilm formation.
      One of the proposed mechanisms is via inhibition of extracellular polysaccharide
      synthesis, which promote the sucrose-dependent adhesion of oral bacteria as S.
      sobrinus.

PMID- 15163649
TI  - Pharmacokinetic-pharmacodynamic modelling of the electroencephalogram effect of
      imipenem in rats with experimental hypovolaemia or endotoxaemia.
AB  - OBJECTIVES: The epileptogenic activity of imipenem in rats with experimentally
      induced hypovolaemia or endotoxaemia was investigated by pharmacokinetic
      pharmacodynamic modelling of the electroencephalogram effect. METHODS:
      Hypovolaemia was induced by removal of 30% of the blood volume and endotoxaemia
      by intravenous lipopolysaccharide injection. RESULTS: Imipenem clearance and
      volume of distribution values of 16.4+/-1.1 mL/min per kg and 357+/-49 mL/kg
      (mean+/-S.E.M.) in healthy rats (n=5), were significantly reduced in hypovolaemic
      (n=6) and endotoxaemic (n=6) animals. A dose reduction from 250 mg/kg to 120
      mg/kg was necessary in endotoxaemic rats. The pharmacokinetic-pharmacodynamic
      model with an effect compartment previously developed in healthy rats described
      the data adequately and pharmacodynamic parameters in hypovolaemic and
      endotoxaemic rats were not significantly different from corresponding values
      estimated in the control group. CONCLUSION: Hypovolaemia and endotoxaemia only
      had an effect on imipenem pharmacokinetics.

PMID- 15163650
TI  - Post-exposure prophylaxis of systemic anthrax in mice and treatment with
      fluoroquinolones.
AB  - OBJECTIVES: To compare the fluoroquinolones gatifloxacin and moxifloxacin with
      ciprofloxacin for post-exposure prophylaxis of systemic anthrax in a BALB/c mouse
      model. METHODS: Treated mice and controls were inoculated subcutaneously with 5 x
      10(4) spores/mouse of Bacillus anthracis Ames strain and observed for 37 days
      after challenge. Treated mice were given 100 mg/kg of antibiotic orally twice
      daily for 14 days, starting at various times post-challenge. RESULTS: Treatment
      starting 6 h post-challenge resulted in survival rates of 90%, 15% and 40% for
      gatifloxacin, moxifloxacin and ciprofloxacin, respectively. Treatment commencing
      24 h post-challenge resulted in survival rates of 65%, 10% and 5%, respectively.
      Treatment starting more than 24 h after exposure had little effect on survival.
      CONCLUSIONS: Gatifloxacin appeared to be more effective than moxifloxacin or
      ciprofloxacin, at similar doses, for early post-exposure treatment of murine
      systemic anthrax. However, these results might be due to differences in potency
      or pharmacokinetic properties.

PMID- 15163651
TI  - A double-blind randomized controlled trial of fusidic acid and metronidazole for
      treatment of an initial episode of Clostridium difficile-associated diarrhoea.
AB  - OBJECTIVES: Few treatment options are currently available to treat patients
      suffering from an initial episode of Clostridium difficile-associated diarrhoea
      (CDAD). PATIENTS AND METHODS: A prospective, randomized controlled, double-blind
      trial was conducted to compare the efficacy of fusidic acid and metronidazole for
      treatment of patients experiencing a first episode of CDAD. The primary outcomes
      were clinical cure and clearance of C. difficile toxin determined on days 8-13,
      and secondary outcomes were clinical recurrence and reappearance of C. difficile
      toxin evaluated on days 35-40. RESULTS: Of the patients in the fusidic acid
      group, 83% were clinically cured in comparison to 93% in the metronidazole group
      (P=0.116) at the first follow-up visit. Clearance of C. difficile toxin did not
      differ between the two groups at that time. Clinical recurrence and reappearance
      of C. difficile toxin were noted in 27% and in 13% of the patients receiving
      fusidic acid, respectively and in 29% and 10% of those given metronidazole at the
      second follow-up on days 35-40. CONCLUSION: Since three of the four primary and
      secondary outcomes were almost identical for the two groups, the results indicate
      that fusidic acid is as effective as metronidazole in curing an initial episode
      of CDAD and can therefore be considered as an adequate alternative for treatment
      of this disease.

PMID- 15163652
TI  - Targeting Leishmania (L.) chagasi amastigotes through macrophage scavenger
      receptors: the use of drugs entrapped in liposomes containing phosphatidylserine.
AB  - OBJECTIVES: We devised liposome-entrapped antimony with the negatively charged
      lipid phosphatidylserine-liposome-entrapped antimony (Sb-LP)-in order to improve
      their targeting to infected macrophages through the interaction with scavenger
      receptors (SRs). METHODS: SR production was indirectly evaluated by its mRNA
      synthesis in infected and uninfected peritoneal macrophages using RT-PCR. The
      interaction and cytotoxicity of Sb-LP with SRs and their metabolism were
      determined by incubation with macrophages in the presence of cytochalasin B,
      chloroquine or different competitive ligands, with determination of the 50%
      inhibitory concentration (IC50) in vitro in infected macrophages. The
      intracellular trafficking of Sb-LP was evaluated by confocal microscopy using
      trapped fluorescent dyes. RESULTS: Our results showed an up-regulation of
      macrophage SR mRNA during the initial steps of Leishmania (L.) chagasi infection.
      By competitive ligand assays, we demonstrated the preferential uptake of Sb-LP by
      macrophage SRs. Sb-LP was 16-fold more effective (IC50=14.11 microM) than the
      free drug (IC50=225.9 microM) against L. (L.) chagasi-infected macrophages. The
      binding and uptake of Sb-LP in macrophages were shown to be energy-dependent and
      were reduced in the presence of cytochalasin B, showing the dependency of the
      cell microfilament system. Confocal analysis using trapped fluorescent dyes
      showed fluorescence of parasites or in their close proximity, compatible with the
      localized delivery of the liposomes. CONCLUSIONS: The uptake of Sb-LP was reduced
      in infected macrophages, despite their effectiveness and targeting ability,
      suggesting a low metabolic rate in infected macrophages that could be overcome by
      the higher efficiency of the liposomal formulation. These in vitro results
      suggest that liposomes could improve the therapeutic index of old drugs, such as
      pentavalent antimony, via targeted delivery to Leishmania-infected cells.

PMID- 15163653
TI  - Pre-exposure of infected human endometrial epithelial cells to penicillin in
      vitro renders Chlamydia trachomatis refractory to azithromycin.
AB  - OBJECTIVE: The clinical significance of the potential for persistent human
      chlamydial infections in vivo is being actively reassessed because of the
      increased frequency of recurrent infection with the same serovar despite
      compliance with an effective antibiotic regimen. The ability to extend the length
      of time of in vitro cultivation of polarized human endometrial epithelial cells
      (HEC-1B) provided the opportunity to establish a model system to determine if a
      persistent form of Chlamydia trachomatis had the same susceptibility as the
      actively growing form to a cidal concentration of azithromycin. METHODS:
      Polarized HEC-1B cells cultivated on extracellular matrix were infected with C.
      trachomatis serovar E and exposed to penicillin at 24 h post-infection (hpi) to
      induce a persistent infection characterized by slowly metabolizing but non
      dividing, ultrastructurally aberrant reticulate bodies within the chlamydial
      inclusion; at 48 hpi, infected cultures were exposed to a bactericidal
      concentration of azithromycin for 72 h. RESULTS: Persistent chlamydiae were
      phenotypically resistant to azithromycin; the number of chlamydial inclusions on
      subpassage of progeny from persistent chlamydiae following removal of penicillin
      and recovery was essentially the same as from progeny from persistent chlamydiae
      following removal of penicillin and azithromycin and recovery. Neutrophils were
      attracted in vitro to persistently infected HEC-1B cells that had been exposed to
      penicillin and azithromycin. CONCLUSIONS: Thus, this study provides evidence at
      the cellular microbiology level in vitro for mechanisms that could exist in vivo
      to create sustained, but perhaps clinically inapparent inflammation, which might
      eventually lead to conditions such as silent pelvic inflammatory disease.

PMID- 15163654
TI  - Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and
      incidence of Clostridium difficile diarrhoea.
AB  - OBJECTIVES: We followed the effects of changes to a new antibiotic policy
      favouring a ureidopenicillin as opposed to a third-generation cephalosporin on
      the long-term incidence of Clostridium difficile diarrhoea (CDD) and antibiotic
      utilization in a large Elderly Medicine Unit. PATIENTS AND METHODS: In 1999,
      piperacillin-tazobactam was added to the formulary in Elderly Medicine and its
      use promoted in preference to cefotaxime. Following review and feedback to
      clinicians of surveillance data, cefotaxime prescribing was actively restricted
      during 2000-2001. An audit of prescriber adherence to antibiotic policy was
      carried out by reviewing the records of 159 patients during February-April 2001.
      In December 2001, due to manufacturer production problems, supply of piperacillin
      tazobactam was stopped. We performed standardized period prevalence surveillance
      (February-April) allowing comparisons of antibiotic utilization and CDD incidence
      during the 5 year study period (1998-2002). RESULTS: CDD incidence did not change
      significantly (P>0.1) during 1998-1999 despite a marked increase in piperacillin
      tazobactam prescribing. However, when cefotaxime prescribing was curtailed in
      2001, CDD rates decreased (in four of five wards) and overall by 52% (P=0.008).
      When piperacillin-tazobactam became unavailable in 2002, despite advice to the
      contrary cefotaxime prescribing rose five-fold, and CDD rates increased in four
      of five wards and by 232% (P<0.01) overall. Adherence to antibiotic policy
      introduced in 2000 was good (81% accordance); 94%, 88% and 73% of patients with
      cellulitis, urinary tract and respiratory tract infection, respectively, received
      appropriate antibiotics. CONCLUSIONS: Long-term prescribing of piperacillin
      tazobactam in Elderly Medicine in preference to cefotaxime is associated with
      reduced rates of CDD. However, unless cephalosporin prescribing is curtailed, the
      beneficial effects on CDD rates may be missed. This is one of few studies to
      document adverse effects due to loss of antibiotic supply.

PMID- 15163655
TI  - Antiviral prophylaxis of smallpox.
AB  - Proof-of-concept studies suggest that current defences against smallpox could be
      strengthened by supplementing vaccination with antiviral drug prophylaxis, based
      on aerosolized or orally available forms of the long-acting medication cidofovir.
      Delivery of aerosolized cidofovir to mice results in its prolonged retention in
      respiratory tissues and protection against lethal intranasal or aerosol poxviral
      challenge. Although cidofovir itself is not orally available, the addition of an
      alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal
      tract. This also markedly increases its antiviral activity and lengthens its
      intracellular half-life from roughly 3 to 8-10 days. Oral treatment also
      protected mice against lethal poxviral challenge. These results suggest that a
      single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could
      provide prolonged protection against initiation of smallpox infection, whereas
      oral treatment could prevent both initiation of infection and internal
      dissemination of virus. Both approaches may avoid the nephrotoxicity that
      occasionally results from intravenous cidofovir therapy.

PMID- 15163656
TI  - Starting highly active antiretroviral therapy: why, when and response to HAART.
AB  - Highly active antiretroviral therapy (HAART) has dramatically improved the
      prognosis of patients with HIV, although it remains unclear as to the best time
      to start treatment to reduce the risk of clinical progression. The initial
      virological response to HAART, by reducing viral load to below the limit of
      detection, is essential for reducing the risk of drug resistance, which in the
      longer term may lead to a deterioration in immune function and an increased risk
      of clinical disease progression. There has been a switch to more conservative
      therapy recently, given concerns about toxicities and the difficulties of
      adhering to a complicated regimen long term.

PMID- 15163657
TI  - A long-term latent reservoir for HIV-1: discovery and clinical implications.
AB  - Despite the remarkable success of highly active antiretroviral therapy (HAART)
      for the treatment of HIV-1 infection, it now appears that the infection is
      intrinsically incurable with antiretroviral therapy alone. The major reason is
      that the virus can persist in a latent form in resting memory CD4 cells. These
      cells arise when infected CD4+ lymphoblasts carrying an integrated copy of the
      HIV-1 genome revert back to a resting memory state. In this resting state, CD4
      cells are minimally permissive for virus gene expression, and infected memory
      cells can survive for many years. Following re-exposure to the relevant antigen
      or other activating stimuli, these cells can begin to produce virus again. The
      existence of a stable reservoir has altered treatment strategies in several ways.
      HAART is no longer given with the goal of eradication. In addition, the reservoir
      serves as a permanent archive for wild-type virus and for drug-resistant variants
      that arise during treatment. Thus, once resistance to a particular drug arises,
      the patient will always carry that resistance. Interruption in treatment results
      in the re-emergence of the original wild-type virus, which often replicates
      better than drug-resistant virus. Although HAART cannot eradicate the infection,
      current regimens do come close to stopping virus evolution. Free viruses found in
      the plasma at low levels in patients on HAART resemble viruses in the latent
      reservoir and do not contain new drug resistance mutations. Thus although HAART
      cannot produce eradication, lifetime control of the infection with antiretroviral
      drugs may be possible.

PMID- 15163658
TI  - Substantially increased faecal carriage of vancomycin-resistant enterococci in a
      tertiary Greek hospital after a 4 year time interval.
AB  - OBJECTIVES: In a tertiary Greek hospital with no documented vancomycin-resistant
      enterococci (VRE) infections, a cross-sectional study was conducted in order to
      determine the degree of VRE faecal carriage among adult patients hospitalized in
      high-risk units. METHODS: Specimens for the surveillance were collected from
      separate patients in two periods (January-May 1999 and January-May 2003); 258
      specimens were submitted during the first period and 149 during the second
      period. RESULTS: Three patients (1.2%) were colonized with VRE during the first
      period, whereas 52 (34.9%) were colonized during the second period. Two VRE
      isolates of the first period were Enterococcus faecalis and one Enterococcus
      faecium, whereas those of the second period were E. faecium except for three E.
      faecalis and two Enterococcus gallinarum. All VRE isolates apart from the two E.
      gallinarum isolates were positive for the vanA gene. The 48 vancomycin-resistant
      E. faecium were classified into eight clonal types, one of those predominating
      with 29 isolates; the remaining included one to nine isolates. The five
      vancomycin-resistant E. faecalis formed four distinct clonal types. CONCLUSIONS:
      The study reports a substantially higher prevalence of VRE carriage when the
      surveillance was repeated after a 4 year time interval. Urgent infection control
      measures are needed to prevent emergence of VRE outbreaks in our hospital
      setting.

PMID- 15163659
TI  - Biochemical and structural characterization of (South)-methanocarbathymidine that
      specifically inhibits growth of herpes simplex virus type 1 thymidine kinase
      transduced osteosarcoma cells.
AB  - Two analogs of the natural nucleoside dT featuring a pseudosugar with fixed
      conformation in place of the deoxyribosyl residue (carbathymidine analogs) were
      biochemically and structurally characterized for their acceptance by both human
      cytosolic thymidine kinase isoenzyme 1 (hTK1) and herpes simplex virus type 1
      thymidine kinase (HSV1 TK) and subsequently tested in cell proliferation assays.
      3'-exo-Methanocarbathymidine ((South)-methanocarbathymidine (S)-MCT), which is a
      substrate for HSV1 TK, specifically inhibited growth of HSV1 TK-transduced human
      osteosarcoma cells with an IC(50) value in the range of 15 microM without
      significant toxicity toward both hTK1-negative (TK(-)) and non-transduced cells.
      2'-exo-Methanocarbathymidine ((North)-methanocarbathymidine (N)-MCT), which is a
      weak substrate for hTK1 and a substantial one for HSV1 TK, induced a specific
      growth inhibition in HSV1 TK-transfected cells comparable to that of (S)-MCT and
      ganciclovir. A growth inhibition activity was also observed with (N)-MCT and
      ganciclovir in non-transduced cells in a cell line-dependent manner, whereas TK(
      ) cells were not affected. The presented 1.95-A crystal structure of the complex
      (S)-MCT.HSV1 TK explains both the more favorable binding affinity and catalytic
      turnover of (S)-MCT for HSV1 TK over the North analog. Additionally the
      plasticity of the active site of the enzyme is addressed by comparing the binding
      of (North)- and (South)-carbathymidine analogs. The presented study of these two
      potent candidate prodrugs for HSV1 TK gene-directed enzyme prodrug therapy
      suggests that (S)-MCT may be even safer to use than its North counterpart (N)
      MCT.

PMID- 15163660
TI  - Substrate-induced conformational changes in human UMP/CMP kinase.
AB  - Human UMP/CMP kinase plays a crucial role in supplying precursors for nucleic
      acid synthesis by catalyzing the conversion of UMP, CMP, and dCMP into their
      diphosphate form. In addition, this kinase is an essential component of the
      activation cascade of medicinally relevant nucleoside analog prodrugs such as
      AraC, gemcitabine, and ddC. During the catalytic cycle the enzyme undergoes large
      conformational changes from open in the absence of substrates to closed in the
      presence of both phosphoryl donor and phosphoryl acceptor. Here we report the
      crystal structure of the substrate-free, open form of human UMP/CMP kinase.
      Comparison of the open structure with the closed state previously reported for
      the similar Dictyostelium discoideum UMP/CMP kinase reveals the conformational
      changes that occur upon substrate binding. We observe a classic example of
      induced fit where substrate-induced conformational changes in hinge residues
      result in rigid body movements of functional domains to form the catalytically
      competent state. In addition, a homology model of the human enzyme in the closed
      state based on the structure of D. discoideum UMP/CMP kinase aids to rationalize
      the substrate specificity of the human enzyme.

PMID- 15163661
TI  - Ubiquitin-Proteasome-mediated degradation of Id1 is modulated by MyoD.
AB  - Degradation of many short-lived cellular proteins such as the transcription
      factor MyoD occurs via the ubiquitin-proteasome pathway. MyoD, similar to many
      rapidly degraded regulatory factors, interacts with several high affinity binding
      partners, including members of the Id (inhibitors of DNA binding) family.
      Following transfection to HeLa cells, Id1 is localized to the nucleus and rapidly
      (t(1/2) approximately 1 h) degraded via the ubiquitin-proteasome system.
      Mutagenesis of lysine residues within the putative nuclear localization region
      (amino acids 68-82) directs Id1(NLS) to the cytoplasm yet confers an increased
      rate of degradation (t(1/2) approximately 0.5 h). Id1 in which all lysine
      residues were mutagenized to alanine (lysineless Id1) was also rapidly degraded
      (t(1/2) approximately 0.6 h). Addition of a Myc(6) tag to the N terminus of
      lysine-less Id1 markedly stabilized Id1 (t(1/2) > 10 h) and suggests degradation
      via the N terminus-dependent pathway. Co-transfection of MyoD with Id1 or
      Id1(NLS) increases Id1 or Id1(NLS) within the nucleus and markedly reduces the
      rate of Id1 or Id1(NLS) degradation. These results thus demonstrate that in vivo
      MyoD modulates the rate of Id1 degradation and suggest a dynamic interplay of
      these factors.

PMID- 15163662
TI  - Deacetylase inhibitors and the viral transactivator TaxBLV synergistically
      activate bovine leukemia virus gene expression via a cAMP-responsive element- and
      cAMP-responsive element-binding protein-dependent mechanism.
AB  - Efficient bovine leukemia virus (BLV) transcription requires the virus-encoded
      transactivator Tax(BLV), which acts through three Tax(BLV)-responsive elements
      located in the 5' long terminal repeat. It has been proposed that the binding of
      the CRE-binding protein (CREB) and the activating transcription factor (ATF) to
      the three imperfect cAMP-responsive elements (CREs) located in each Tax(BLV)
      responsive element mediates Tax(BLV) transactivation. Here we demonstrated that
      deacetylase inhibitors (HDACis) synergistically enhanced the transcriptional
      activation of the BLV promoter by Tax(BLV) in a CRE-dependent manner. Tax(BLV)
      was acetylated in vivo at its N(alpha) terminus but not at internal lysine
      residues. Rather, HDACi potentiation of Tax(BLV) transactivation was mediated by
      an HDACi indirect action that requires new protein synthesis. Mechanistically,
      using a dominant-negative form of CREB, we showed that Tax(BLV) and HDACi
      synergistically activated BLV gene expression via a CREB-dependent mechanism.
      Moreover, electrophoretic mobility shift assay and Western blot experiments
      revealed that HDACi increased the in vitro DNA binding activity of CREB/ATF but
      did not alter CREB/ATF intranuclear presence. Remarkably, chromatin
      immunoprecipitation assays demonstrated that HDACi treatment increased the level
      of CREB bound to the BLV promoter in vivo. Our results together suggest that an
      increase in CREB/ATF occupancy of the viral CREs in response to HDACi potentiates
      Tax(BLV) transactivation of the BLV promoter.

PMID- 15163663
TI  - Potyviral NIa proteinase, a proteinase with novel deoxyribonuclease activity.
AB  - The NIa proteinase from pepper vein banding virus (PVBV) is a sequence-specific
      proteinase required for processing of viral polyprotein in the cytoplasm. It
      accumulates in the nucleus of the infected plant cell and forms inclusion bodies.
      The function of this protein in the nucleus is not clear. The purified
      recombinant NIa proteinase was active, and the mutation of the catalytic residues
      His-46, Asp-81, and Cys-151 resulted in complete loss of activity. Most
      interesting, the PVBV NIa proteinase exhibited previously unidentified activity,
      namely nonspecific double-stranded DNA degradation. This DNase activity of the
      NIa proteinase showed an absolute requirement for Mg(2+). Site-specific
      mutational analysis showed that of the three catalytic residues, Asp-81 was the
      crucial residue for DNase activity. Mutation of His-46 and Cys-151 had no effect
      on the DNase activity, whereas mutant D81N was partially active, and D81G was
      completely inactive. Based on kinetic analysis and molecular modeling, a metal
      ion-dependent catalysis similar to that observed in other nonspecific DNases is
      proposed. Similar results were obtained with glutathione S-transferase-fused PVBV
      NIa proteinase and tobacco etch virus NIa proteinase, confirming that the DNase
      function is an intrinsic property of potyviral NIa proteinase. The NIa protein
      present in the infected plant nuclear extract also showed the proteinase and the
      DNase activities, suggesting that the PVBV NIa protein that accumulates in the
      nucleus late in the infection cycle might serve to degrade the host DNA. Thus the
      dual function of the NIa proteinase could play an important role in the life
      cycle of the virus.

PMID- 15163664
TI  - Identification and characterization of a functional nuclear localization signal
      in the HIV-1 integrase interactor LEDGF/p75.
AB  - Human lens epithelium-derived growth factor (LEDGF)/p75 protein forms a specific
      nuclear complex with human immunodeficiency virus type 1 (HIV-1) integrase and is
      essential for nuclear localization and chromosomal association of the viral
      protein. We now studied nuclear import of LEDGF/p75 in live and semipermeabilized
      cells. We show that nuclear import of LEDGF/p75 is GTP-, Ran-, importin
      alpha/beta-, and energy-dependent and that the protein competes with the
      canonical SV40 large T antigen nuclear localization signal (NLS) for nuclear
      import receptors. We identified the NLS of LEDGF/p75 through deletion analysis
      and site-directed mutagenesis. The LEDGF/p75 NLS, 148GRKRKAEKQ156, belongs to the
      canonical SV40-like family. Fusion of this short peptide to the amino terminus of
      Escherichia coli beta-galactosidase rendered the fusion protein nuclear,
      confirming that the LEDGF/p75 NLS is transferable. Moreover, a single amino acid
      change in the NLS was sufficient to exclude the mutant LEDGF/p75 protein from the
      nucleus and abolish nuclear import of HIV-1 integrase.

PMID- 15163665
TI  - Impaired platelet activation in familial high density lipoprotein deficiency
      (Tangier disease).
AB  - ATP binding cassette transporter A1 (ABCA1) is involved in regulation of
      intracellular lipid trafficking and export of cholesterol from cells to high
      density lipoproteins. ABCA1 defects cause Tangier disease, a disorder
      characterized by absence of high density lipoprotein and thrombocytopenia. In the
      present study we have demonstrated that ABCA1 is expressed in human platelets and
      that fibrinogen binding and CD62 surface expression in response to collagen and
      low concentrations of thrombin, but not to ADP, are defective in platelets from
      Tangier patients and ABCA1-deficient animals. The expression of platelet membrane
      receptors such as GPVI, alpha2beta1 integrin, and GPIIb/IIIa, the collagen
      induced changes in phosphatidylserine and cholesterol distribution, and the
      collagen-induced signal transduction examined by phosphorylation of LAT and
      p72syk and by intracellular Ca2+ mobilization were unaltered in Tangier
      platelets. The electron microscopy of Tangier platelets revealed reduced numbers
      of dense bodies and the presence of giant granules typically encountered in
      platelets from Chediak-Higashi syndrome. Further studies demonstrated impaired
      release of dense body content in platelets from Tangier patients and ABCA1
      deficient animals. In addition, Tangier platelets were characterized by defective
      surface exposure of dense body and lysosomal markers (CD63, LAMP-1, LAMP-2, CD68)
      during collagen- and thrombin-induced stimulation and by abnormally high
      lysosomal pH. We conclude that intact ABCA1 function is necessary for proper
      maturation of dense bodies in platelets. The impaired release of the content of
      dense bodies may explain the defective activation of Tangier platelets by
      collagen and low concentrations of thrombin, but not by ADP.

PMID- 15163666
TI  - The N terminus of Myxococcus xanthus CarA repressor is an autonomously folding
      domain that mediates physical and functional interactions with both operator DNA
      and antirepressor protein.
AB  - Expression of the Myxococcus xanthus carB operon, which encodes the majority of
      the enzymes involved in light-induced carotenogenesis, is down-regulated in the
      dark by the CarA repressor binding to its bipartite operator. CarS, produced on
      illumination, relieves repression of carB by physically interacting with CarA to
      dis-mantle CarA-DNA complexes. Here, we demonstrate that the N- and C-terminal
      portions of CarA are organized as distinct structural and functional domains.
      Specifically, we show that the 78 N-terminal residues of CarA, CarA(Nter), form a
      monomeric, highly helical, autonomously folding unit with significant structural
      stability. Significantly, CarA(Nter) houses both the operator and CarS binding
      specificity determinants of CarA. CarA(Nter) binds operator with a lower affinity
      than whole CarA, and the CarA(Nter)-CarS complex has a 1:1 stoichiometry. In
      vitro, sufficiently high concentrations of CarA(Nter) block M. xanthus RNA
      polymerase-promoter binding, and this is relieved by CarS. In vivo, substitution
      of the gene carA by that for CarA(Nter) results in constitutive expression of
      carB just as in a carA-deleted background. However, re-engineering the latter
      strain to overexpress CarA(Nter) restores repression of carB. Thus, the 78
      residue N-terminal portion of CarA is an autonomously folded, dual function
      domain that orchestrates specific DNA-protein and protein-protein interactions
      and, when overexpressed, can be functionally competent in vivo.

PMID- 15163667
TI  - Sympathetic influence on capsaicin-evoked enhancement of dorsal root reflexes in
      rats.
AB  - A series of experiments by our group suggest that the initiation and development
      of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes
      (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary
      afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from
      single afferent fibers in the proximal ends of cut dorsal root filaments at the
      L4-L6 level and tested for responses to intradermal injection of capsaicin.
      Sympathectomy combined with pharmacological manipulations were employed to
      determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic
      modulation. DRRs could be recorded from both myelinated (Abeta and Adelta) and
      unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into
      the plantar foot, a significant enhancement of DRRs was seen in C- and Adelta
      fibers but not in Abeta-fibers. This enhancement of DRRs evoked by capsaicin
      injection was almost completely prevented by sympathectomy. However, if
      peripheral alpha1-adrenoceptors were activated by intra-arterial injection of
      phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored,
      whereas no such restoration was seen following pretreatment with an alpha2
      adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the
      enhanced DRRs following capsaicin injection could be blocked by administration of
      terazosin, an alpha1-adrenoceptor antagonist, but not by administration of
      yohimbine, an alpha2-adrenoceptor antagonist. These results provide further
      evidence that the DRR-mediated neurogenic inflammation depends in part on intact
      sympathetic efferents acting on peripheral alpha1-adrenoceptors, which augment
      the sensitization of primary afferent nociceptors induced by capsaicin injection,
      helping trigger DRRs that produce vasodilation.

PMID- 15163668
TI  - Functional properties of grasping-related neurons in the dorsal premotor area F2
      of the macaque monkey.
AB  - We investigated the properties of neurons located in the distal forelimb field of
      dorsal premotor area F2 of macaque monkey using a behavioral paradigm for
      studying the neuronal discharge during observation (object fixation condition)
      and grasping of different 3-dimensional objects with and without visual guidance
      of the movement (movement in light and movement in dark conditions,
      respectively). The main result is that almost all studied neurons were selective
      for both the type of prehension and the wrist orientation required for grasping
      an object. Three categories of neurons were found: purely motor, visually
      modulated, and visuomotor neurons. The discharge of purely motor neurons was not
      affected by either object presentation or by the visual feedback of the hand
      approaching to and interacting with the object. Visually modulated neurons
      presented a different discharge in the 2 movement conditions, this determining a
      decrease in selectivity for the grip and wrist orientation in the movement in
      dark condition. Visuomotor neurons typically discharged during the object
      fixation task even in the absence of any grasping movement. Nine of them also
      displayed a different discharge rate between the 2 movement conditions.
      Congruence was observed between the neuron response during the most effective
      type of prehension and the neuron response during observation of the object
      requiring that particular prehension. These results indicate an important role of
      F2 in the control of goal-related hand movements.

PMID- 15163669
TI  - A possible role of midbrain dopamine neurons in short- and long-term adaptation
      of saccades to position-reward mapping.
AB  - Dopamine (DA) neurons respond to sensory stimuli that predict reward. To
      understand how DA neurons acquire such ability, we trained monkeys on a one
      direction-rewarded version of memory-guided saccade task (1DR) only when we
      recorded from single DA neurons. In 1DR, position-reward mapping was changed
      across blocks of trials. In the early stage of training of 1DR, DA neurons
      responded to reward delivery; in the later stages, they responded predominantly
      to the visual cue that predicted reward or no reward (reward predictor)
      differentially. We found that such a shift of activity from reward to reward
      predictor also occurred within a block of trials after position-reward mapping
      was altered. A main effect of long-term training was to accelerate the within
      block reward-to-predictor shift of DA neuronal responses. The within-block shift
      appeared first in the intermediate stage, but was slow, and DA neurons often
      responded to the cue that indicated reward in the preceding block. In the
      advanced stage, the reward-to-predictor shift occurred quickly such that the DA
      neurons' responses to visual cues faithfully matched the current position-reward
      mapping. Changes in the DA neuronal responses co-varied with the reward
      predictive differentiation of saccade latency both in short-term (within-block)
      and long-term adaptation. DA neurons' response to the fixation point also
      underwent long-term changes until it occurred predominantly in the first trial
      within a block. This might trigger a switch between the learned sets. These
      results suggest that midbrain DA neurons play an essential role in adapting
      oculomotor behavior to frequent switches in position-reward mapping.

PMID- 15163670
TI  - Response properties of whisker-related neurons in rat second somatosensory
      cortex.
AB  - In addition to a primary somatosensory cortex (SI), the cerebral cortex of all
      mammals contains a second somatosensory area (SII); however, the functions of SII
      are largely unknown. Our aim was to explore the functions of SII by comparing
      response properties of whisker-related neurons in this area with their
      counterparts in the SI. We obtained extracellular unit recordings from narcotized
      rats, in response to whisker deflections evoked by a piezoelectric device, and
      compared response properties of SI barrel (layer IV) neurons with those of SII
      (layers II to VI) neurons. Neurons in both cortical areas have similar response
      latencies and spontaneous activity levels. However, SI and SII neurons differ in
      several significant properties. The receptive fields of SII neurons are at least
      five times as large as those of barrel neurons, and they respond equally strongly
      to several principal whiskers. The response magnitude of SII neurons is
      significantly smaller than that of neurons in SI, and SII neurons are more
      selective for the angle of whisker deflection. Furthermore, whereas in SI fast
      spiking (inhibitory) and regular-spiking (excitatory) units have different
      spontaneous and evoked activity levels and differ in their responses to stimulus
      onset and offset, SII neurons do not show significant differences in these
      properties. The response properties of SII neurons suggest that they are driven
      by thalamic inputs that are part of the paralemniscal system. Thus whisker
      related inputs are processed in parallel by a lemniscal system involving SI and a
      paralemniscal system that processes complimentary aspects of somatosensation.

PMID- 15163672
TI  - Auditory saccades from different eye positions in the monkey: implications for
      coordinate transformations.
AB  - Auditory spatial information arises in a head-centered coordinate frame, whereas
      the saccade command signals generated by the superior colliculus (SC) are thought
      to specify target locations in an eye-centered frame. However, auditory activity
      in the SC appears to be neither head- nor eye-centered but in a reference frame
      that is intermediate between both of these reference frames. This
      neurophysiological finding suggests that auditory saccades might not fully
      compensate for changes in initial eye position. Here, we investigated whether the
      accuracy of saccades to sounds is affected by initial eye position in rhesus
      monkeys. We found that, on average, a 12 degrees horizontal shift in initial eye
      position produced only a 0.6 to 1.6 degrees horizontal shift in the endpoints of
      auditory saccades made to targets at a range of locations along the horizontal
      meridian. This shift was similar in size to the modest influence of eye position
      on visual saccades. This virtually complete compensation for initial eye position
      implies that auditory activity in the SC is read out in a manner that is
      appropriate for generating accurate saccades to sounds.

PMID- 15163671
TI  - A-current expression is regulated by activity but not by target tissues in
      developing lumbar motoneurons of the chick embryo.
AB  - The functional expression of A-type K+ channels (IA) was examined in chick lumbar
      motoneurons (LMNs) at embryonic days 6 and 11 (E6 and E11). We observed a
      threefold increase in IA density between E6 and E11 in spinal cord slices and
      acutely dissociated LMNs. There was no change in current density, kinetics, or
      voltage dependence of IA in E11 homozygous limbless mutants or in E11 embryos in
      which hindlimbs were surgically removed at E6. Moreover, chronic in ovo
      administration of D-tubocurarine, which causes an increase in motoneuron
      branching on the surface of target muscles, had no effect on IA. Electrical
      activity played an important role in IA regulation in LMNs in vitro and in ovo.
      Blocking spontaneous electrical activity of LMNs by chronic in ovo application of
      mecamylamine or muscimol reduced IA by 80%. LMNs cultured in the presence of TTX
      also failed to express normal densities of IA, even when the cultures also
      contained target tissues. The portion of IA that remained after in ovo or in
      vitro blockade of activity inactivated more quickly than the IA of LMNs that were
      allowed to discharge spikes. The developmental expression of LMN IA increases
      significantly during development, and this increase is activity dependent but
      does not require interactions with target tissues. Ongoing activity also seems to
      regulate the kinetics of IA inactivation.

PMID- 15163673
TI  - Lamina I, but not lamina V, spinothalamic neurons exhibit responses that
      correspond with burning pain.
AB  - Single-unit recordings from monkey spinothalamic tract (STT) neurons reveal that
      the responses of polymodal nociceptive lamina I STT neurons correspond with the
      profile of burning pain elicited in human subjects by repeated brief-contact
      heat. In contrast, lamina V wide-dynamic-range (WDR) neurons show a significantly
      different response pattern. This finding indicates that burning pain is signaled
      by modality-selective lamina I neurons and not convergent lamina V WDR neurons.

PMID- 15163674
TI  - Contribution of Ih and GABAB to synaptically induced afterhyperpolarizations in
      CA1: a brake on the NMDA response.
AB  - CA1 pyramidal cells receive two major excitatory inputs: the perforant path (PP)
      terminates in the most distal dendrites, whereas the Schaffer collaterals (SC)
      terminate more proximally. We have examined the mechanism of the
      afterhyperpolarization (AHP) that follows single subthreshold excitatory
      postsynaptic potentials (EPSPs) in these inputs. The AHPs were not reduced by a
      GABAA antagonist or by agents that block Ca2+ entry. Application of the Ih
      blocker, ZD7288, partially blocked the AHP in the PP; the substantial remaining
      component was blocked by 2-hydroxysaclofen, a GABAB antagonist. In contrast, the
      AHP in the SC depends nearly completely on Ih, with almost no GABAB component.
      Thus postsynaptic GABAB receptors appear to be preferentially involved at distal
      synapses, consistent with the spatial distribution of GABAB receptors and g
      protein-coupled inward rectifying potassium (GIRK) channels. GABAB does, however,
      play a role at proximal synapses through presynaptic suppression of glutamate
      release, a mechanism that is much weaker at distal synapses. Experiments were
      conducted to explore the functional role of the AHP in the PP, which has a higher
      N-methyl-D-aspartate (NMDA)/AMPA ratio than the SC. Blockade of the AHP converted
      a response that had a small NMDA component to one that had a large component.
      These results indicate that the Ih and postsynaptic GABAB conductances act as a
      brake on distally generated NMDA responses.

PMID- 15163675
TI  - Properties of primary motor cortex output to forelimb muscles in rhesus macaques.
AB  - Stimulus-triggered averaging (StTA) of electromyographic (EMG) activity from 24
      simultaneously recorded forelimb muscles was used to investigate properties of
      primary motor cortex (M1) output in the macaque monkey. Two monkeys were trained
      to perform a reach-to-grasp task requiring multijoint coordination of the
      forelimb. EMG activity was recorded from 24 forelimb muscles including 5
      shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles.
      Microstimulation (15 microA at 15 Hz) was delivered throughout the movement task.
      From 297 stimulation sites in M1, a total of 2,079 poststimulus effects (PStE)
      were obtained including 1,398 poststimulus facilitation (PStF) effects and 681
      poststimulus suppression (PStS) effects. Of the PStF effects, 60% were in distal
      and 40% in proximal muscles; 43% were of extensors and 47% flexors. For PStS, the
      corresponding numbers were 55 and 45% and 36 and 55%, respectively. M1 output
      effects showed extensive cofacilitation of proximal and distal muscles (96 sites,
      42%) including 47 sites that facilitated at least one shoulder, elbow, and distal
      muscle, 45 sites that facilitated an elbow muscle and a distal muscle, and 22
      sites that facilitated at least one muscle at all joints. The muscle synergies
      represented by outputs from these sites may serve an important role in the
      production of coordinated, multijoint movements. M1 output effects showed many
      similarities with red nucleus output although red nucleus effects were generally
      weaker and showed a strong bias toward facilitation of extensor muscles and a
      greater tendency to facilitate synergies involving muscles at noncontiguous
      joints.

PMID- 15163676
TI  - Patterns of muscle activity underlying object-specific grasp by the macaque
      monkey.
AB  - During object grasp, a coordinated activation of distal muscles is required to
      shape the hand in relation to the physical properties of the object. Despite the
      fundamental importance of the grasping action, little is known of the muscular
      activation patterns that allow objects of different sizes and shapes to be
      grasped. In a study of two adult macaque monkeys, we investigated whether we
      could distinguish between EMG activation patterns associated with grasp of 12
      differently shaped objects, chosen to evoke a wide range of grasping postures.
      Each object was mounted on a horizontal shuttle held by a weak spring (load force
      1-2 N). Objects were located in separate sectors of a "carousel," and inter-trial
      rotation of the carousel allowed sequential presentation of the objects in
      pseudorandom order. EMG activity from 10 to 12 digit, hand, and arm muscles was
      recorded using chronically implanted electrodes. We show that the grasp of
      different objects was characterized by complex but distinctive patterns of EMG
      activation. Cluster analysis shows that these object-related EMG patterns were
      specific and consistent enough to identify the object unequivocally from the EMG
      recordings alone. EMG-based object identification required a minimum of six EMGs
      from simultaneously recorded muscles. EMG patterns were consistent across
      recording sessions in a given monkey but showed some differences between animals.
      These results identify the specific patterns of activity required to achieve
      distinct hand postures for grasping, and they open the way to our understanding
      of how these patterns are generated by the central motor network.

PMID- 15163677
TI  - Cerebral areas processing swallowing and tongue movement are overlapping but
      distinct: a functional magnetic resonance imaging study.
AB  - Although multiple regions of the cerebral cortex have been implicated in
      swallowing, the functional contributions of each brain area remain unclear. The
      present study sought to clarify the roles of these cortical foci in swallowing by
      comparing brain activation associated with voluntary saliva swallowing and
      voluntary tongue elevation. Fourteen healthy right-handed subjects were examined
      with single-event-related functional magnetic resonance imaging (fMRI) while
      laryngeal movements associated with swallowing and tongue movement were
      simultaneously recorded. Both swallowing and tongue elevation activated 1) the
      left lateral pericentral and anterior parietal cortex, and 2) the anterior
      cingulate cortex (ACC) and adjacent supplementary motor area (SMA), suggesting
      that these brain regions mediate processes shared by swallowing and tongue
      movement. Tongue elevation activated a larger total volume of cortex than
      swallowing, with significantly greater activation within the ACC, SMA, right
      precentral and postcentral gyri, premotor cortex, right putamen, and thalamus.
      Although a contrast analysis failed to identify activation foci specific to
      swallowing, superimposed activation maps suggested that the most lateral extent
      of the left pericentral and anterior parietal cortex, rostral ACC, precuneus, and
      right parietal operculum/insula were preferentially activated by swallowing. This
      finding suggests that these brain areas may mediate processes specific to
      swallowing. Approximately 60% of the subjects showed a strong functional
      lateralization of the postcentral gyrus toward the left hemisphere for
      swallowing, whereas 40% showed a similar activation bias for the tongue elevation
      task. This finding supports the view that the oral sensorimotor cortices within
      the left and right hemispheres are functionally nonequivalent.

PMID- 15163678
TI  - Modulation of locomotor activity by multiple 5-HT and dopaminergic receptor
      subtypes in the neonatal mouse spinal cord.
AB  - Recently, it has been shown that bath-applied 5-HT can elicit fictive locomotion
      from perinatal mouse preparations. Since 5-HT acts on multiple receptor subtypes,
      the focus of this study was to examine which receptor families contribute to the
      genesis and modulation of locomotor activity. Blockade of 5-HT(2) (ketanserin or
      N-desmethylclozapine) or 5-HT(7) receptors (SB-269970) could reversibly block or
      modulate the locomotor-like pattern. A 5-HT(2) agonist (alpha-methyl-5-HT) was
      shown to be capable of activating the rhythm. Bath application of 5-HT(7)
      agonists (5-CT) generally led to a tonic increase in neurogram discharge,
      accompanied by bouts of rhythmic activity. Blockade of dopaminergic receptors
      (D(1) [R-(+)-SCH-23390 or LE 300]/D(2) [(+/-)-sulpiride or L-741,626] ) could
      reversibly disrupt the rhythm and most effectively did so when the D(1) and D(2)
      antagonists were added together. Conversely, 5-HT(2) and D(1)/D(2) agonists can
      interact to evoke locomotor activity. Overall, our data show that, in the
      neonatal mouse preparation, 5-HT evoked locomotion is partly dependent on
      activation of 5-HT(2), 5-HT(7), and dopaminergic receptor subtypes.

PMID- 15163679
TI  - Effect of quinidine on the 10-hydroxylation of R-warfarin: species differences
      and clearance projection.
AB  - Stimulation by quinidine of warfarin metabolism in vitro was first demonstrated
      with liver microsomal preparations. We report herein that this drug interaction
      is reproducible in an animal model but that it exhibits profound species
      differences. Thus, using rabbit liver microsomes and a kinetic model
      incorporating two binding sites, the hepatic intrinsic clearance of R-warfarin
      via the 10-hydroxylation pathway (CL(int)(W)) was projected to be 6 +/- 1 and 128
      +/- 51 microl/min/g liver, respectively, in the absence and presence of 21 microM
      unbound quinidine. These estimates were consistent with the results from studies
      in which rabbit livers (n = 5) were perfused in situ with R-warfarin or R
      warfarin plus quinidine. The CL(int)(W) increased from 7 +/- 3 to 156 +/- 106
      microl/min/g liver after increasing the hepatic exposure of unbound quinidine
      from 0 to 21 microM. In contrast, when liver microsomes or intact livers from
      rats were examined, R-warfarin metabolism was inhibited by quinidine, the
      CL(int)(W) decreasing to 26% of the control value after exposure of perfused rat
      livers (n = 5) to 22 microM unbound quinidine. The third example involved monkey
      liver microsomes, in which the rate of 10-hydroxylation of R-warfarin was little
      affected in the presence of quinidine (<2-fold increase). In all three species,
      the 10-hydroxylation of R-warfarin was catalyzed primarily by members of CYP3A,
      based on immuno- and chemical inhibition analyses. These findings not only
      highlight the variability of drug interactions among different species but also
      suggest that changes in hepatic clearance resulting from stimulation of
      cytochrome P450 activity may be projected based on estimates generated from
      corresponding liver microsomal preparations.

PMID- 15163680
TI  - Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is
      associated with microglial activation.
AB  - Methamphetamine intoxication causes long-lasting damage to dopamine nerve endings
      in the striatum. The mechanisms underlying this neurotoxicity are not known but
      oxidative stress has been implicated. Microglia are the major antigen-presenting
      cells in brain and when activated, they secrete an array of factors that cause
      neuronal damage. Surprisingly, very little work has been directed at the study of
      microglial activation as part of the methamphetamine neurotoxic cascade. We
      report here that methamphetamine activates microglia in a dose-related manner and
      along a time course that is coincident with dopamine nerve ending damage.
      Prevention of methamphetamine toxicity by maintaining treated mice at low ambient
      temperature prevents drug-induced microglial activation. MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine), which damages dopamine nerve endings and cell
      bodies, causes extensive microglial activation in striatum as well as in the
      substantia nigra. In contrast, methamphetamine causes neither microglial
      activation in the substantia nigra nor dopamine cell body damage. Dopamine
      transporter antagonists (cocaine, WIN 35,428 [(-)-2-beta-carbomethoxy-3-beta-(4
      fluorophenyl)tropane 1,5-naphthalenedisulfonate], and nomifensine), selective D1
      (SKF 82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine hydrobromide]), D2 (quinpirole), or mixed D1/D2 receptor agonists
      (apomorphine) do not mimic the effect of methamphetamine on microglia.
      Hyperthermia, a prominent and dangerous clinical response to methamphetamine
      intoxication, was also ruled out as the cause of microglial activation. Together,
      these data suggest that microglial activation represents an early step in
      methamphetamine-induced neurotoxicity. Other neurochemical effects resulting from
      methamphetamine-induced overflow of DA into the synapse, but which are not
      neurotoxic, do not play a role in this response.

PMID- 15163681
TI  - Multiple, developmentally regulated expression mechanisms of long-term
      potentiation at CA1 synapses.
AB  - Long-term potentiation (LTP) of AMPA receptor-mediated synaptic transmission at
      hippocampal CA1 synapses has been extensively studied, but the mechanisms
      responsible for its expression remain unresolved. We tested a hypothesis that
      there are multiple, developmentally regulated expression mechanisms by directly
      comparing LTP in hippocampal slices obtained from rats of two ages. At postnatal
      day 12 (P12), LTP was fully accounted for by an increase in potency (mean
      amplitude of responses excluding failures). This was associated with either an
      increase in AMPA receptor single-channel conductance (gamma) or no change in
      gamma, suggesting an increase in the number of AMPA receptors. At P6, LTP was
      explained by an additional two mechanisms. In the majority of neurons, LTP was
      associated with an increase in success rate and a decrease in paired-pulse
      facilitation. In the remaining neurons, LTP was attributable to an increase in
      potency. However, in contrast to P12 neurons, the potency increase was associated
      with a decrease in gamma, suggesting the insertion of receptors with lower gamma.
      We conclude that there are multiple expression mechanisms for LTP at CA1 synapses
      that are developmentally regulated. These findings suggest that a single class of
      synapse uses a number of different molecular mechanisms to produce long-term
      changes in synaptic strength.

PMID- 15163682
TI  - Encoding-specific effects of social cognition on the neural correlates of
      subsequent memory.
AB  - To examine whether social cognition recruits distinct mental operations, we
      measured brain activity during social ("form an impression of this person") and
      relatively nonsocial ("remember the order in which person information is
      presented") orienting tasks. Extending previous research on the neural basis of
      social cognition, the impression formation task differentially engaged an
      extensive region of the dorsomedial prefrontal cortex (PFC). In contrast, the
      nonsocial sequencing task differentially engaged the superior frontal and
      parietal gyri, precentral gyrus, and the caudate. In addition, we compared
      encoding activations for subsequently remembered (i.e., hits) to subsequently
      forgotten (i.e., misses) items. The brain regions in which the blood oxygenation
      level-dependent signal distinguished subsequent hits from subsequent misses
      depended on which orienting task was performed at encoding: subsequent memory was
      correlated with encoding activity only in the medial PFC for impression formation
      trials but in the right hippocampus for sequencing trials. These data inform two
      interrelated cognitive issues. First, results underscore the neuroanatomical
      distinctiveness of social cognition and suggest that previous psychological
      theories may have neglected important functional differences in how the human
      brain instantiates social and nonsocial cognitive processes. Second, by
      demonstrating that activity in different brain regions correlates with subsequent
      memory as a function of the orienting task performed at encoding, these data
      provide evidence of the neural basis for encoding specificity, the principle that
      memory is critically determined by the cognitive process engaged by the initial
      study episode.

PMID- 15163683
TI  - Visualization of glucocorticoid receptor and mineralocorticoid receptor
      interactions in living cells with GFP-based fluorescence resonance energy
      transfer.
AB  - Adrenal corticosteroids readily enter the brain and exert markedly diverse
      effects, including stress responses in the target neural cells via two receptor
      systems, the mineralocorticoid receptor (MR) and the glucocorticoid receptor
      (GR). It has been shown that the GR and MR are highly colocalized in the
      hippocampus. Given the differential action of the MR and GR in the hippocampal
      region, it is important to elucidate how these receptors interact with each other
      in response to corticosteroids. We investigated the heterodimerization of the MR
      and GR with green fluorescent protein-based fluorescence resonance energy
      transfer (FRET) microscopy in living cells with spatiotemporal manner. FRET was
      evaluated in three ways: (1) ratio imaging; (2) emission spectra; and (3)
      acceptor photobleaching. FRET analysis demonstrated that cyan fluorescent protein
      GR and yellow fluorescent protein-MR form heterodimers after corticosterone
      (CORT) treatment both in the nucleus of cultured hippocampal neurons and COS-1
      cells, whereas they do not form heterodimers in the cytoplasm. The content of the
      GR-MR heterodimer was higher at 10(-6) m CORT than at 10(-9) m CORT and reached a
      maximum level after 60 min of CORT treatment in both cultured hippocampal neurons
      and COS-1 cells. The distribution pattern of heterodimers in the nucleus of
      cultured hippocampal neurons was more restricted than that in COS-1 cells. The
      present study using mutant fusion proteins in nuclear localization signal showed
      that these corticosteroid receptors are not translocated into the nucleus in the
      form of heterodimers even after treatment with ligand and thus allow no
      heterodimerization to take place in the cytoplasm. These results obtained with
      FRET analyses give new insights into the sites, time course, and effects of
      ligand concentration on heterodimersization of the GR and MR.

PMID- 15163684
TI  - Long-term alterations in neuroimmune responses after neonatal exposure to
      lipopolysaccharide.
AB  - Fever is an integral part of the host's defense to infection that is orchestrated
      by the brain. A reduced febrile response is associated with reduced survival.
      Consequently, we have asked if early life immune exposure will alter febrile and
      neurochemical responses to immune stress in adulthood. Fourteen-day-old neonatal
      male rats were given Escherichia coli lipopolysaccharide (LPS) that caused either
      fever or hypothermia depending on ambient temperature. Control rats were given
      pyrogen-free saline. Regardless of the presence of neonatal fever, adult animals
      that had been neonatally exposed to LPS displayed attenuated fevers in response
      to intraperitoneal LPS but unaltered responses to intraperitoneal interleukin
      1beta or intracerebroventricular prostaglandin E(2). The characteristic reduction
      in activity that accompanies fever was unaltered, however, as a function of
      neonatal LPS exposure. Treatment of neonates with an antigenically dissimilar LPS
      (Salmonella enteritidis) was equally effective in reducing adult responses to E.
      coli LPS, indicating an alteration in the innate immune response. In adults
      treated as neonates with LPS, basal levels of hypothalamic cyclooxygenase 2 (COX
      2), determined by semiquantitative Western blot analysis, were significantly
      elevated compared with controls. In addition, whereas adult controls responded to
      LPS with the expected induction of COX-2, adults pretreated neonatally with LPS
      responded to LPS with a reduction in COX-2. Thus, neonatal LPS can alter CNS
      mediated inflammatory responses in adult rats.

PMID- 15163685
TI  - Firing mode-dependent synaptic plasticity in rat neocortical pyramidal neurons.
AB  - Pyramidal cells in the mammalian neocortex can emit action potentials either as
      series of individual spikes or as distinct clusters of high-frequency bursts.
      However, why two different firing modes exist is largely unknown. In this study,
      we report that in layer V pyramidal cells of the rat somatosensory cortex, in
      vitro associations of EPSPs with spike bursts delayed by +10 msec led to long
      term synaptic depression (LTD), whereas pairings with individual action
      potentials at the same delay induced long-term potentiation. EPSPs were evoked
      extracellularly in layer II-III and recorded intracellularly in layer V neurons
      with the whole-cell or nystatin-based perforated patch-clamp technique. Bursts
      were evoked with brief somatic current injections, resulting in three to four
      action potentials with interspike frequencies of approximately 200 Hz,
      characteristic of intrinsic burst firing. Burst-firing-associated LTD (Burst-LTD)
      was robust over a wide range of intervals between -100 and +200 msec, and
      depression was maximal (approximately 50%) for closely spaced presynaptic and
      postsynaptic events. Burst-LTD was associative and required concomitant
      activation of low voltage-activated calcium currents and metabotropic glutamate
      receptors. Conversely, burst-LTD was resistant to blockade of NMDA receptors or
      inhibitory synaptic potentials. Burst-LTD was also inducible at already
      potentiated synapses. We conclude that intrinsic burst firing represents a signal
      for resetting excitatory synaptic weights.

PMID- 15163686
TI  - Effects of the lurcher mutation on GluR1 desensitization and activation kinetics.
AB  - Previous studies of the lurcher mutation in GluR1 channels concluded that its
      main effect is to create constitutively active channels (Kohda et al., 2000;
      Taverna et al., 2000). GluR1Lc channels also exhibit slowed kinetics and a shift
      in their apparent affinity for glutamate (Kohda et al., 2000; Taverna et al.,
      2000). Here, we have undertaken a kinetic analysis of GluR1Lc channels to
      quantify the effects of lurcher and to determine the relative contribution of
      these effects to the lurcher phenotype. Analysis of GluR1Lc leak current
      demonstrated that the 2,3-dioxo-6-nitro-1,2,3,4-tetrahydro[f]quinoxaline-7
      sulfonamide (NBQX)-sensitive portion of the leak current corresponded to a
      current generated by glutamate concentrations similar to the levels of
      contaminating glutamate measured in our normal external solutions. This result,
      and the small size of the leak current relative to the currents evoked by
      saturating glutamate, indicates that GluR1Lc channels exhibit little or no
      constitutive activity. Our results indicate that the primary effect of the
      lurcher mutation is to increase the affinity of GluR1 for glutamate and reduce
      the desensitization of GluR1 at nanomolar concentrations. We also found that the
      mutation makes both the rate and extent of GluR1Lc channel desensitization depend
      strongly on subunit occupancy. We conclude that the poor survival of GluR1Lc
      transfected cells, and presumably cerebellar neurons in lurcher mice, results
      because channels carrying the lurcher mutation open and do not desensitize at
      ambient levels of glutamate.

PMID- 15163687
TI  - Rescuing transient corticospinal terminations and promoting growth with
      corticospinal stimulation in kittens.
AB  - Development of corticospinal (CS) terminations is activity dependent. In the cat,
      activity-dependent refinement of termination topography occurs between weeks 3
      and 6. Initially, sparse terminals are present in the gray matter bilaterally,
      including the motor nuclei. By week 6, virtually all motor nuclear terminations
      are eliminated, as are most ipsilateral terminations. In this study, we
      determined whether electrical stimulation of CS axons could be used to rescue
      transient terminations and promote their growth. We implanted microwires in the
      pyramid or spinal white matter to stimulate CS axons (2 hr/d, 330 Hz, 45 msec
      burst, 2 sec intervals) for 2-3 weeks during the refinement period. CS
      terminations were traced using wheat germ agglutinin conjugated to horseradish
      peroxidase. Animals were killed after week 6. Stimulation produced dense
      terminations bilaterally, including within the motor nuclei. Termination density
      was least in lamina 1 and ventral lamina 9. Reticular formation stimulation
      produced a control (i.e., nonstimulated) termination pattern. To determine
      whether CS stimulation affected development of the nonstimulated CS system, we
      traced terminations from the contralateral cortex using biotinylated dextran
      amine. Compared with controls or after reticular formation stimulation, there was
      a shift in the distribution of terminations of the nonstimulated side to more
      dorsal laminas, which is where the stimulated CS system had fewer terminals. This
      distribution shift is consistent with competition for termination space between
      the CS systems on both sides. Our findings indicate that activity can be
      harnessed to bias CS axon terminal development. This has important implications
      for using activity to modify motor system organization after perinatal CNS
      trauma.

PMID- 15163688
TI  - A dissociation of motion and spatial-pattern vision in the avian telencephalon:
      implications for the evolution of "visual streams".
AB  - The ectostriatum is a large visual structure in the avian telencephalon. Part of
      the tectofugal pathway, the ectostriatum receives a large ascending thalamic
      input from the nucleus rotundus, the homolog of the mammalian pulvinar complex.
      We investigated the effects of bilateral lesions of the ectostriatum in pigeons
      on visual motion and spatial-pattern perception tasks. To test motion perception,
      we measured performance on a task requiring detection of coherently moving random
      dots embedded in dynamic noise. To test spatial-pattern perception, we measured
      performance on the detection of a square wave grating embedded in static noise. A
      double dissociation was revealed. Pigeons with lesions to the caudal ectostriatum
      showed a performance deficit on the motion task but not the grating task. In
      contrast, pigeons with lesions to the rostral ectostriatum showed a performance
      deficit on the grating task but not the motion task. Thus, in the avian
      telencephalon, there is a separation of visual motion and spatial-pattern
      perception as there is in the mammalian telencephalon. However, this separation
      of function is in the targets of the tectofugal pathway in pigeons rather than in
      the thalamofugal pathway as described in mammals. The implications of these
      findings with respect to the evolution of the visual system are discussed.
      Specifically, we suggest that the principle of parallel visual streams originated
      in the tectofugal pathway rather than the thalamofugal pathway.

PMID- 15163689
TI  - An analysis of the neural representation of birdsong memory.
AB  - Songbirds, such as zebra finches, learn their song from a tutor early in life.
      Forebrain nuclei in the "song system" are important for the acquisition and
      production of song. Brain regions [including the caudomedial part of the
      neostriatum (NCM) and of the hyperstriatum ventrale (CMHV)] outside the song
      system show increased neuronal activation, measured as expression of immediate
      early genes (IEGs), when zebra finch males are exposed to song. IEG expression in
      the NCM in response to tutor song is significantly positively correlated with the
      strength of song learning (i.e., the number of elements copied). Here, we exposed
      three groups of adult zebra finch males to tutor song, to their own song, or to
      novel conspecific song. The two control groups were included to examine an
      alternative explanation of our previous results in terms of variation in
      predisposed levels of attentiveness. Expression of Zenk, the protein product of
      the IEG ZENK, was measured in the NCM, CMHV, and hippocampus. There were no
      significant differences in overall Zenk expression between the three experimental
      groups. However, there was a significant positive correlation between Zenk
      expression in the NCM (but not in the other two regions) and strength of song
      learning in the males that were exposed to the tutor song. There was no such
      correlation in the other two groups. These results suggest that experience
      related neuronal activation is specific to the tutor song and thus unlikely to be
      a result of differences in attention.

PMID- 15163690
TI  - Endocannabinoid-independent retrograde signaling at inhibitory synapses in layer
      2/3 of neocortex: involvement of vesicular glutamate transporter 3.
AB  - Recent studies implicate dendritic endocannabinoid release from subsynaptic
      dendrites and subsequent inhibition of neurotransmitter release from nerve
      terminals as a means of retrograde signaling in multiple brain regions. Here we
      show that type 1 cannabinoid receptor-mediated endocannabinoid signaling is not
      involved in the retrograde control of synaptic efficacy at inhibitory synapses
      between fast-spiking interneurons and pyramidal cells in layer 2/3 of the
      neocortex. Vesicular neurotransmitter transporters, such as vesicular glutamate
      transporters (VGLUTs) 1 and 2, are localized to presynaptic terminals and
      accumulate neurotransmitters into synaptic vesicles. A third subtype of VGLUTs
      (VGLUT3) was recently identified and found localized to dendrites of various cell
      types. We demonstrate, using multiple immunofluorescence labeling and confocal
      laser-scanning microscopy, that VGLUT3-like immunoreactivity is present in
      dendrites of layer 2/3 pyramidal neurons in the rat neocortex. Electron
      microscopy analysis confirmed that VGLUT3-like labeling is localized to vesicular
      structures, which show a tendency to accumulate in close proximity to
      postsynaptic specializations in dendritic shafts of pyramidal cells. Dual whole
      cell recordings revealed that retrograde signaling between fast-spiking
      interneurons and pyramidal cells was enhanced under conditions of maximal
      efficacy of VGLUT3-mediated glutamate uptake, whereas it was reduced when
      glutamate uptake was inhibited by incrementing concentrations of the nonselective
      VGLUT inhibitor Evans blue (0.5-5.0 microm) or intracellular Cl- concentrations
      (4-145 mm). Our results present further evidence that dendritic vesicular
      glutamate release, controlled by novel VGLUT isoforms, provides fast negative
      feedback at inhibitory neocortical synapses, and demonstrate that glutamate can
      act as a retrograde messenger in the CNS.

PMID- 15163691
TI  - An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by
      retinal ganglion cells.
AB  - In the mammalian CNS, glial cells repel axons during development and inhibit axon
      regeneration after injury. It is unknown whether the same repulsive axon guidance
      molecules expressed by glia and their precursors during development also play a
      role in inhibiting regeneration in the injured CNS. Here we investigate whether
      optic nerve glial cells express semaphorin family members and, if so, whether
      these semaphorins inhibit axon growth by retinal ganglion cells (RGCs). We show
      that each optic nerve glial cell type, astrocytes, oligodendrocytes, and their
      precursor cells, expressed a distinct complement of semaphorins. One of these,
      sema5A, was expressed only by purified oligodendrocytes and their precursors, but
      not by astrocytes, and was present in both normal and axotomized optic nerve but
      not in peripheral nerves. Sema5A induced collapse of RGC growth cones and
      inhibited RGC axon growth when presented as a substrate in vitro. To determine
      whether sema5A might contribute to inhibition of axon growth after injury, we
      studied the ability of RGCs to extend axons when cultured on postnatal day (P) 4,
      P8, and adult optic nerve explants and found that axon growth was strongly
      inhibited. Blocking sema5A using a neutralizing antibody significantly increased
      RGC axon growth on these optic nerve explants. These data support the hypothesis
      that sema5A expression by oligodendrocyte lineage cells contributes to the glial
      cues that inhibit CNS regeneration.

PMID- 15163692
TI  - Corticotropin-releasing factor and acute stress prolongs serotonergic regulation
      of GABA transmission in prefrontal cortical pyramidal neurons.
AB  - The stress-related neuropeptide corticotropin-releasing factor (CRF) and the
      serotonin system are both critically involved in the pathophysiology of mental
      disorders, including anxiety and depression. To understand the potential link
      between them, we investigated the impact of CRF on 5-HT functions in pyramidal
      neurons of the prefrontal cortex (PFC), a brain region that is crucial for the
      control of emotion and cognition. One prominent function of serotonin in PFC is
      to regulate GABAergic inhibitory transmission, as indicated by a 5-HT-induced
      large, desensitizing (approximately 4 min) enhancement of the amplitude and
      frequency of spontaneous IPSCs (sIPSCs). In PFC slices exposed to CRF treatment,
      the regulation of sIPSCs by 5-HT was significantly prolonged (8-10 min), and this
      effect of CRF was blocked by treatment with the competitive CRF receptor
      antagonist alpha-helical CRF9-41 and with the CRF-R1-specific antagonist
      astressin. Inhibiting phospholipase C or protein kinase C (PKC) abolished the
      prolongation by CRF of the effects of 5-HT on sIPSCs. In PFC slices prepared from
      animals previously exposed to acute stress (forced swim or elevated platform),
      the regulation of sIPSCs by 5-HT was significantly prolonged, mimicking the
      effect of CRF treatment. The stress-induced prolongation of the effects of 5-HT
      on sIPSCs was diminished by alpha-helical CRF9-41 treatment, mimicked by direct
      activation of PKC, and reversed by short-term treatment with drugs that have
      anxiolytic efficacy. These results show that in response to stressful stimuli,
      CRF alters the serotonergic regulation of GABA transmission through a mechanism
      that is dependent on PKC. The interaction between CRF and 5-HT may play an
      important role in psychiatric disorders, in which both are highly implicated.

PMID- 15163694
TI  - Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of
      astrocytic processes and improves post-traumatic regeneration.
AB  - The regenerative capacity of the CNS is extremely limited. The reason for this is
      unclear, but glial cell involvement has been suspected, and oligodendrocytes have
      been implicated as inhibitors of neuroregeneration (Chen et al., 2000, GrandPre
      et al., 2000; Fournier et al., 2001). The role of astrocytes in this process was
      proposed but remains incompletely understood (Silver and Miller, 2004). Astrocyte
      activation (reactive gliosis) accompanies neurotrauma, stroke, neurodegenerative
      diseases, or tumors. Two prominent hallmarks of reactive gliosis are hypertrophy
      of astrocytic processes and upregulation of intermediate filaments. Using the
      entorhinal cortex lesion model in mice, we found that reactive astrocytes devoid
      of the intermediate filament proteins glial fibrillary acidic protein and
      vimentin (GFAP-/-Vim-/-), and consequently lacking intermediate filaments
      (Colucci-Guyon et al., 1994; Pekny et al., 1995; Eliasson et al., 1999), showed
      only a limited hypertrophy of cell processes. Instead, many processes were
      shorter and not straight, albeit the volume of neuropil reached by a single
      astrocyte was the same as in wild-type mice. This was accompanied by remarkable
      synaptic regeneration in the hippocampus. On a molecular level, GFAP-/-Vim-/-
      reactive astrocytes could not upregulate endothelin B receptors, suggesting that
      the upregulation is intermediate filament dependent. These findings show a novel
      role for intermediate filaments in astrocytes and implicate reactive astrocytes
      as potent inhibitors of neuroregeneration.

PMID- 15163693
TI  - An experiment of nature: brain anatomy parallels cognition and behavior in
      Williams syndrome.
AB  - Williams syndrome (WS) is a neurogenetic-neurodevelopmental disorder
      characterized by a highly variable and enigmatic profile of cognitive and
      behavioral features. Relative to overall intellect, affected individuals
      demonstrate disproportionately severe visual-spatial deficits and enhanced
      emotionality and face processing. In this study, high-resolution magnetic
      resonance imaging data were collected from 43 individuals with WS and 40 age- and
      gender-matched healthy controls. Given the distinct cognitive-behavioral
      dissociations associated with this disorder, we hypothesized that neuroanatomical
      integrity in WS would be diminished most in regions comprising the visual-spatial
      system and most "preserved" or even augmented in regions involved in emotion and
      face processing. Both volumetric analysis and voxel-based morphometry were used
      to provide convergent approaches for detecting the hypothesized WS
      neuroanatomical profile. After adjusting for overall brain volume, participants
      with WS showed reduced thalamic and occipital lobe gray matter volumes and
      reduced gray matter density in subcortical and cortical regions comprising the
      human visual-spatial system compared with controls. The WS group also showed
      disproportionate increases in volume and gray matter density in several areas
      known to participate in emotion and face processing, including the amygdala,
      orbital and medial prefrontal cortices, anterior cingulate, insular cortex, and
      superior temporal gyrus. These findings point to specific neuroanatomical
      correlates for the unique topography of cognitive and behavioral features
      associated with this disorder.

PMID- 15163695
TI  - Partial deletion of the cAMP response element-binding protein gene promotes
      alcohol-drinking behaviors.
AB  - The cAMP response element-binding protein (CREB) gene transcription factor has
      been shown to play a role in the synaptic plasticity associated with drug
      addictive behaviors; however, the causal role of the CREB gene in alcohol
      drinking behaviors is unknown. The present investigation evaluated alcohol
      drinking behaviors in mice that are haplodeficient in CREB as a result of
      targeted CREB (alpha and Delta) gene disruption. It was found that CREB
      haplodeficient (+/-) mice have higher preference for ethanol but not for sucrose
      solution than wild-type (+/+) littermates. The functional aspects of the CREB
      gene transcription factor were also investigated by measuring the protein levels
      of phosphorylated CREB (p-CREB) and the expression of cAMP-inducible genes such
      as neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF). Deletion of
      the CREB (alpha and Delta) gene significantly decreases total CREB, p-CREB levels
      and the expression of NPY and BDNF in the brain structures of CREB-deficient (+/
      ) mice. It was also found that CREB-deficient (+/-) mice displayed more anxiety
      like behaviors and that acute ethanol exposure produced anxiolytic effects and
      significantly increased protein levels of p-CREB and NPY in the central and
      medial but not in the basolateral amygdala of wild-type mice, but these effects
      are attenuated in CREB-deficient mice compared with wild-type mice. These results
      provide the first direct evidence that a haplodeficiency of the CREB gene is
      associated with increased alcohol-drinking behaviors. Furthermore, alcohol
      drinking and anxiety-like behaviors in CREB-haplodeficient mice may possibly be
      related to decreased expression of NPY and BDNF in the brains of these mice.

PMID- 15163697
TI  - Modulation of ion channels and synaptic transmission by a human sensory neuron
      specific G-protein-coupled receptor, SNSR4/mrgX1, heterologously expressed in
      cultured rat neurons.
AB  - Human sensory neuron-specific G-protein-coupled receptors (SNSRs) are expressed
      solely in small diameter primary sensory neurons. This restricted expression
      pattern is of considerable therapeutic interest because small nociceptors
      transmit chronic pain messages. The neuronal function of human SNSRs is difficult
      to assess because rodent orthologs have yet to be clearly defined, and individual
      isoforms are found only in a small subset of primary sensory neurons. To
      circumvent this problem, we expressed human SNSR4 (hSNSR4; also known as
      Hs.mrgX1) in rat superior cervical ganglion (SCG), dorsal root ganglion (DRG),
      and hippocampal neurons using nuclear injection or recombinant adenoviruses and
      examined modulation of ion channels and neurotransmission using whole-cell patch
      clamp techniques. BAM8-22 (a 15 amino acid C-terminal fragment of bovine adrenal
      medulla peptide 22), a peptide agonist derived from proenkephalin, inhibited high
      (but not low) voltage-activated Ca2+ current in both DRG and SCG neurons
      expressing hSNSR4, whereas no response was detected in control neurons. The Ca2+
      current inhibition was concentration dependent and partially sensitive to
      Pertussis toxin (PTX) treatment. Additionally, the peptide was highly effective
      in modulating current arising from M-type K+ channels in SCG neurons expressing
      hSNSR4. In hippocampal neurons expressing hSNSR4, BAM8-22 induced presynaptic
      inhibition of transmission that was abolished after PTX treatment. Our data
      indicate that hSNSR4, when heterologously expressed in rat neurons, can be
      activated by an opioid-related peptide, couples to G(q/11)-proteins as well as
      PTX-sensitive G(i/o)-proteins, and modulates neuronal Ca2+ channels, K+ channels,
      and synaptic transmission.

PMID- 15163696
TI  - GABA( A) synapses shape neuronal responses to sound intensity in the inferior
      colliculus.
AB  - Neurons in the inferior colliculus (IC) change their firing rates with sound
      pressure level. Some neurons maintain monotonic increases in firing rate over a
      wide range of sound intensities, whereas other neurons are monotonic over limited
      intensity ranges. We examined the conditions necessary for monotonicity in this
      nucleus in vitro in rat brain slices and in vivo in the unanesthetized rabbit.
      Our in vitro recordings indicate that concurrent activation of GABA(A) synapses
      with excitatory inputs facilitates monotonic increases in firing rate with
      increases in stimulus strength. In the absence of synaptic inhibition, excitatory
      input to IC neurons causes large depolarizations that result in firing block and
      nonmonotonicity. In vivo, although GABA(A) synapses decrease the firing rate in
      all IC neurons, they can have opposing effects on rate-level functions. GABAergic
      inputs activated by all sound intensities maintain monotonicity by keeping the
      postsynaptic potential below the level at which depolarization block occurs. When
      these inputs are blocked, firing block can occur and rate-level functions become
      nonmonotonic. High-threshold GABAergic inputs, in contrast, cause nonmonotonic
      responses by decreasing the firing rate at high intensities. Our results suggest
      that a dynamic regulation of the postsynaptic membrane potential by synaptic
      inhibition is necessary to allow neurons to respond monotonically to a wide range
      of sound intensities.

PMID- 15163698
TI  - Inhibition of neurotransmitter release by a nonphysiological target requires
      protein synthesis and involves cAMP-dependent and mitogen-activated protein
      kinases.
AB  - During the development of neuronal circuits, axonal growth cones can contact many
      inappropriate targets before they reach an appropriate postsynaptic partner.
      Although it is well known that the contact with synaptic partners upregulates the
      secretory machinery of the presynaptic neuron, little is known about the
      signaling mechanisms involved in preventing the formation of connections with
      inappropriate target cells. Here, we show that the contact with a
      nonphysiological postsynaptic target inhibits neurotransmitter release from
      axonal terminals of the Helix serotonergic neuron C1 by means of an active
      mechanism requiring ongoing protein synthesis and leading to the inhibition of
      cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (MAPK)
      extracellular signal-related kinase (Erk) pathways. The reversal of the
      inhibitory effect of the nonphysiological target by blockade of protein synthesis
      was prevented by cAMP-PKA or MAPK-Erk inhibitors, whereas disinhibition of
      neurotransmitter release promoted by cAMP-PKA activation was not affected by MAPK
      Erk inhibitors. The data indicate that the inhibitory effect of the
      nonphysiological target on neurotransmitter release is an active process that
      requires protein synthesis and involves the downregulation of the MAPK-Erk and
      cAMP-PKA pathways, the same protein kinases that are activated after contact with
      a physiological target neuron. These mechanisms could play a relevant role in the
      prevention of synapse formation between inappropriate partners by modulating the
      neurotransmitter release capability of growing nerve terminals according to the
      nature of the targets contacted during their development.

PMID- 15163699
TI  - Subclinical bovine spongiform encephalopathy infection in transgenic mice
      expressing porcine prion protein.
AB  - The bovine-porcine species barrier to bovine spongiform encephalopathy (BSE)
      infection was explored by generating transgenic mouse lines expressing the
      porcine prion protein (PrP) gene. All of the porcine transgenic (poTg) mice
      showed clinical signs of BSE after intracerebral inoculation with a high-titer
      BSE inoculum. The protease-resistant PrP (PrP(res)) was detected in 14% (3 of 22)
      of the BSE-infected poTg mice by immunohistochemical or immunoblot analysis.
      Despite being able to infect 42% (5 of 12) of control mice, a low-dose BSE
      inoculum failed to penetrate the species barrier in our poTg mouse model. The
      findings of these infectivity studies suggest that there is a strong species
      barrier between cows and pigs. However, after second-passage infection of poTg
      mice using brain homogenates of BSE-inoculated mice scoring negative for the
      incoming prion protein as inoculum, it was possible to detect the presence of the
      infectious agent. Thus, porcine-adapted BSE inocula were efficient at infecting
      poTg mice, giving rise to an incubation period substantially reduced from 300 to
      177 d after inoculation and to the presence of PrP(res) in 100% (21 of 21) of the
      mice. We were therefore able to conclude that initial exposure to the bovine
      prion may lead to subclinical infection such that brain homogenates from poTg
      mice classified as uninfected on the basis of the absence of PrP(res) are
      infectious when used to reinoculate poTg mice. Collectively, our findings suggest
      that these poTg mice could be used as a sensitive bioassay model for prion
      detection in pigs.

PMID- 15163700
TI  - Hippocampal place cells are not controlled by visual input during the small
      irregular activity state in the rat.
AB  - In the actively foraging rat, hippocampal pyramidal cells have strong spatial
      correlates. Each "place cell" fires rapidly only when the rat enters a particular
      delimited portion of its environment, called the "place field" of that cell.
      Hippocampal pyramidal cells also exhibit spatial selectivity during a
      physiological state that occurs during sleep, termed "small irregular activity"
      (SIA), because of the appearance of the hippocampal EEG. It is not known whether
      rats determine their current location in space during SIA using current visual
      information or whether they recall the location in which they fell asleep. To
      address this question, we recorded spikes from ensembles of CA1 pyramidal cells
      and hippocampal EEG while rats slept along the edge of a large circular recording
      arena with minimal local features in a room with prominent distal visual cues. To
      move the rats to a new location in the room while they were sleeping, we slowly
      rotated the recording arena on which they slept to a new orientation in the room.
      Hippocampal place cell activity in subsequent SIA episodes reflected the location
      in the room in which the rats fell asleep, rather than the location to which they
      were moved, although the alignment of the rats' spatial map was governed by the
      room cues in the subsequent active foraging session. Thus, the hippocampal
      population activity during SIA does not result from the processing of current
      visual information but instead probably reflects a memory for the location in
      which the rat fell asleep.

PMID- 15163701
TI  - Interleukin-13 overexpression by tax transactivation: a potential autocrine
      stimulus in human T-cell leukemia virus-infected lymphocytes.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein induces growth
      transformation and is critical for the pathogenesis of the HTLV-1-induced adult T
      cell leukemia (ATL). It stimulates the cell cycle and transactivates cellular
      genes. Here we show that the expression of interleukin-13 (IL-13) is upregulated
      as a consequence of Tax in HTLV-1-transformed T cells and ATL-derived cultures.
      IL-13 exerts proliferative and antiapoptotic functions and is linked to
      leukemogenesis, since it stimulates Hodgkin lymphoma cells by an autocrine
      mechanism. Overexpression of IL-13 RNA and protein was confirmed in HTLV-1
      positive and Tax-transformed cells. Induction of endogenous IL-13 levels in tax
      transfected Jurkat cells and in conditional Tax-expressing transformed T
      lymphocytes suggested that Tax can replace signals required for IL-13 synthesis.
      For functional analysis, the IL-13 promoter and deletion variants were cloned
      into luciferase reporter plasmids. Experiments with transfected human T
      lymphocytes revealed a 16-fold stimulation of the IL-13 promoter by Tax.
      Experiments with Tax mutants indicated that none of the classical transactivation
      pathways (SRF, CREB, and NF-kappaB) is sufficient for the transactivation; at
      least two different Tax functions are required for full transactivation. The IL
      13 promoter is stimulated via two elements; one is a NF-AT binding P element, and
      the other is a putative AP-1 site. The following observations suggest that IL-13
      may stimulate HTLV-1-transformed cells by an autocrine mechanism: (i) the HTLV-1
      transformed cells express the IL-13 receptor on their surface, and (ii) STAT6, a
      downstream effector of IL-13 signaling, is constitutively activated. Thus, in
      summary, Tax, by transactivating the promoter, induces IL-13 overexpression that
      possibly leads to an autocrine stimulation of HTLV-1-infected cells.

PMID- 15163702
TI  - Requirements for brome mosaic virus subgenomic RNA synthesis in vivo and
      replicase-core promoter interactions in vitro.
AB  - Based solely on in vitro results, two contrasting models have been proposed for
      the recognition of the brome mosaic virus (BMV) subgenomic core promoter by the
      replicase. The first posits that the replicase recognizes at least four key
      nucleotides in the core promoter, followed by an induced fit, wherein some of the
      nucleotides base pair prior to the initiation of RNA synthesis (S. Adkins and C.
      C. Kao, Virology 252:1-8, 1998). The second model posits that a short RNA hairpin
      in the core promoter serves as a landing pad for the replicase and that at least
      some of the key nucleotides help form a stable hairpin (P. C. J. Haasnoot, F.
      Brederode, R. C. L. Olsthoorn, and J. Bol, RNA 6:708-716, 2000; P. C. J.
      Haasnoot, R. C. L. Olsthoorn, and J. Bol, RNA 8:110-122, 2002). We used
      transfected barley protoplasts to examine the recognition of the subgenomic core
      promoter by the BMV replicase. Key nucleotides required for subgenomic initiation
      in vitro were found to be important for RNA4 levels in protoplasts. In addition,
      additional residues not required in vitro and the formation of an RNA hairpin
      within the core promoter were correlated with wild-type RNA4 levels in cells.
      Using a template competition assay, the core promoter of ca. 20 nucleotides was
      found to be sufficient for replicase binding. Mutations of the key residues in
      the core promoter reduced replicase binding, but deletions that disrupt the
      predicted base pairing in the proposed stem retained binding at wild-type levels.
      Together, these results indicate that key nucleotides in the BMV subgenomic core
      promoter direct replicase recognition but that the formation of a stem-loop is
      required at a step after binding. Additional functional characterization of the
      subgenomic core promoter was performed. A portion of the promoter for BMV minus
      strand RNA synthesis could substitute for the subgenomic core promoter in
      transfected cells. The comparable sequence from Cowpea Chlorotic Mottle Virus
      (CCMV) could also substitute for the BMV subgenomic core promoter. However,
      nucleotides in the CCMV core required for RNA synthesis are not identical to
      those in BMV, suggesting that the subgenomic core promoter can induce the BMV
      replicase in interactions needed for subgenomic RNA transcription in vivo.

PMID- 15163703
TI  - The Arabidopsis cucumovirus multiplication 1 and 2 loci encode translation
      initiation factors 4E and 4G.
AB  - The cum1 and cum2 mutations of Arabidopsis thaliana inhibit cucumber mosaic virus
      (CMV) multiplication. In cum1 and cum2 protoplasts, CMV RNA and the coat protein
      accumulated to wild-type levels, but the accumulation of the 3a protein of CMV,
      which is necessary for cell-to-cell movement of the virus, was strongly reduced
      compared with that in wild-type protoplasts. In cum2 protoplasts, the
      accumulation of turnip crinkle virus (TCV)-related RNA and proteins was also
      reduced. Positional cloning demonstrated that CUM1 and CUM2 encode eukaryotic
      translation initiation factors 4E and 4G, respectively. Unlike most cellular
      mRNA, the CMV RNA lacks a poly(A) tail, whereas the TCV RNA lacks both a 5'
      terminal cap and a poly(A) tail. In vivo translation analyses, using chimeric
      luciferase mRNA carrying the terminal structures and untranslated sequences of
      the CMV or TCV RNA, demonstrated that these viral untranslated sequences contain
      elements that regulate the expression of encoded proteins positively or
      negatively. The cum1 and cum2 mutations had different effects on the action of
      these elements, suggesting that the cum1 and cum2 mutations cause inefficient
      production of CMV 3a protein and that the cum2 mutation affects the production of
      TCV-encoded proteins.

PMID- 15163704
TI  - Characterization of the polymerase and RNase H activities of human foamy virus
      reverse transcriptase.
AB  - Foamy virus (FV) replication, while related to that of orthoretroviruses, differs
      at a number of steps. Several of these differences involve the reverse
      transcriptase (RT). There appear to be fewer RTs present in FV than in
      orthoretroviruses; we previously proposed that the polymerase of FV RT was more
      active than orthoretroviral RTs to compensate for the numerical difference. Here
      we present further characterization of the RT of FV. The polymerase activity of
      FV RT was greater than that of human immunodeficiency virus type 1 RT in a
      variety of assays. We also examined the RNase H activity of FV RT, and we propose
      that FV RT has a basic loop in the RNase H domain. Although the sequence of the
      basic loop of FV RT is different from the basic loop of either Moloney leukemia
      virus RNase H or Escherichia coli RNase H, the FV RT basic loop appears to have a
      similar function.

PMID- 15163705
TI  - Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected
      individuals carry integrated HIV-1 genomes within actively transcribed host
      genes.
AB  - Resting CD4+ T-cell populations from human immunodeficiency virus type 1 (HIV-1)
      infected individuals include cells with integrated HIV-1 DNA. In individuals
      showing suppression of viremia during highly active antiretroviral therapy
      (HAART), resting CD4+ T-cell populations do not produce virus without cellular
      activation. To determine whether the nonproductive nature of the infection in
      resting CD4+ T cells is due to retroviral integration into chromosomal regions
      that are repressive for transcription, we used inverse PCR to characterize the
      HIV-1 integration sites in vivo in resting CD4+ T cells from patients on HAART.
      Of 74 integration sites from 16 patients, 93% resided within transcription units,
      usually within introns. Integration was random with respect to transcriptional
      orientation relative to the host gene and with respect to position within the
      host gene. Of integration sites within well-characterized genes, 91% (51 of 56)
      were in genes that were actively expressed in resting CD4+ T cells, as directly
      demonstrated by reverse transcriptase PCR (RT-PCR). These results predict that
      HIV-1 sequences may be included in the primary transcripts of host genes as part
      of rapidly degraded introns. RT-PCR experiments confirmed the presence of HIV-1
      sequences within transcripts initiating upstream of the HIV-1 transcription start
      site. Taken together, these results demonstrate that HIV-1 genomes reside within
      actively transcribed host genes in resting CD4+ T cells in vivo.

PMID- 15163706
TI  - S protein of severe acute respiratory syndrome-associated coronavirus mediates
      entry into hepatoma cell lines and is targeted by neutralizing antibodies in
      infected patients.
AB  - The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes
      severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV
      is not closely related to other coronaviruses but shares a similar genome
      organization. Entry of coronaviruses into target cells is mediated by the viral S
      protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral
      particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the
      cell surface upon transient transfection. Coexpression of SARS-CoV S with human
      immunodeficiency virus-based reporter constructs yielded viruses that were
      infectious for a range of cell lines. Most notably, viral pseudotypes harboring
      SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of
      the hepatoma cell line Huh-7 was also observed with replication-competent SARS
      CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo.
      Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing
      pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection
      by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was
      efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by
      sera from SARS patients, demonstrating that SARS-CoV S is a target for
      neutralizing antibodies and that such antibodies are generated in SARS-CoV
      infected patients. Our results show that viral pseudotyping can be employed for
      the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV
      infection might not be limited to lung tissue and can be inhibited by the humoral
      immune response in infected patients.

PMID- 15163707
TI  - Differential antiviral response of endothelial cells after infection with
      pathogenic and nonpathogenic hantaviruses.
AB  - Hantaviruses represent important human pathogens and can induce hemorrhagic fever
      with renal syndrome (HFRS), which is characterized by endothelial dysfunction.
      Both pathogenic and nonpathogenic hantaviruses replicate without causing any
      apparent cytopathic effect, suggesting that immunopathological mechanisms play an
      important role in pathogenesis. We compared the antiviral responses triggered by
      Hantaan virus (HTNV), a pathogenic hantavirus associated with HFRS, and Tula
      virus (TULV), a rather nonpathogenic hantavirus, in human umbilical vein
      endothelial cells (HUVECs). Both HTNV- and TULV-infected cells showed increased
      levels of molecules involved in antigen presentation. However, TULV-infected
      HUVECs upregulated HLA class I molecules more rapidly. Interestingly, HTNV
      clearly induced the production of beta interferon (IFN-beta), whereas expression
      of this cytokine was barely detectable in the supernatant or in extracts from
      TULV-infected HUVECs. Nevertheless, the upregulation of HLA class I on both TULV-
      and HTNV-infected cells could be blocked by neutralizing anti-IFN-beta
      antibodies. Most strikingly, the antiviral MxA protein, which interferes with
      hantavirus replication, was already induced 16 h after infection with TULV. In
      contrast, HTNV-infected HUVECs showed no expression of MxA until 48 h
      postinfection. In accordance with the kinetics of MxA expression, TULV replicated
      only inefficiently in HUVECs, whereas HTNV-infected cells produced high titers of
      virus particles that decreased after 48 h postinfection. Both hantavirus species,
      however, could replicate equally well in Vero E6 cells, which lack an IFN-induced
      MxA response. Thus, delayed induction of antiviral MxA in endothelial cells after
      infection with HTNV could allow viral dissemination and contribute to the
      pathogenesis leading to HFRS.

PMID- 15163708
TI  - Lack of phenotypic and functional impairment in dendritic cells from chimpanzees
      chronically infected with hepatitis C virus.
AB  - Dendritic cells (DCs), which are potent antigen-presenting cells (APCs), are used
      as adjuvants for the treatment of cancer and infectious diseases in human and
      nonhuman primates, with documented clinical efficacy. The hepatitis C virus (HCV)
      chimpanzee model is the best available model for testing the immunotherapeutic
      effects of DCs in the setting of a chronic infection, as chimpanzees develop a
      persistent infection resembling that seen in humans. However, several reports
      have suggested that DCs derived from chronically infected individuals or nonhuman
      primates are functionally compromised. As a prelude to clinical studies, we
      evaluated whether functionally mature DCs could be generated in chimpanzee plasma
      by good manufacturing practice using CD14(+) mononuclear precursors from
      chronically infected chimpanzees. DCs generated in a medium with HCV-negative
      plasma and treated with a defined cocktail of cytokines or a CD40 ligand trimer
      matured fully, as measured by the induction of CD83 expression and the
      upregulation of costimulatory molecules. Furthermore, the expression of CCR7 was
      induced, suggesting an acquisition of migration capacity. Mature DCs were capable
      of stimulating allogeneic T cells, antigen-specific memory CD4(+) T cells, and
      HCV-specific CD8(+)-T-cell clones. In all cases, there was no evidence of HCV
      infection in DCs. Furthermore, these DCs maintained their phenotype and APC
      function after cryopreservation. Finally, no discernible differences were noted
      between DCs derived from HCV-infected and uninfected chimpanzees. In summary,
      precursor cells from HCV-infected chimpanzees are fully capable of
      differentiating into functional, mature DCs, which can now be reproducibly
      prepared for investigations of their immunotherapeutic potential in the setting
      of chronic HCV infection.

PMID- 15163710
TI  - Inhibition of reovirus by mycophenolic acid is associated with the M1 genome
      segment.
AB  - Mycophenolic acid (MPA), an inhibitor of IMP dehydrogenase, inhibits reovirus
      replication and viral RNA and protein production. In mouse L929 cells, antiviral
      effects were greatest at 30 microg of MPA/ml. At this dosage, MPA inhibited
      replication of reovirus strain T3D more than 1,000-fold and inhibited replication
      of reovirus strain T1L nearly 100-fold, compared to non-drug-treated controls.
      Genetic reassortant analysis indicated the primary determinant of strain-specific
      differences in sensitivity to MPA mapped to the viral M1 genome segment, which
      encodes the minor core protein mu2. MPA also inhibited replication of both
      strains of reovirus in a variety of other cell lines, including Vero monkey
      kidney and U373 human astrocytoma cells. Addition of exogenous guanosine to MPA
      treated reovirus-infected cells restored viral replicative capacity to nearly
      normal levels. These results suggest the mu2 protein is involved in the uptake
      and processing of GTP in viral transcription in infected cells and strengthens
      the evidence that the mu2 protein can function as an NTPase and is likely a
      transcriptase cofactor.

PMID- 15163709
TI  - Differential cellular requirements for activation of herpes simplex virus type 1
      early (tk) and late (gC) promoters by ICP4.
AB  - The herpes simplex virus type 1 immediate-early protein, ICP4, activates the
      transcription of viral early and late genes and is essential for viral growth. It
      has been shown to bind DNA and interact with components of the general
      transcription machinery to activate or repress viral transcription, depending
      upon promoter context. Since early and late gene promoters have different
      architectures and cellular metabolism may be very different at early and late
      times after infection, the cellular requirements for ICP4-mediated activation of
      early and late genes may differ. This hypothesis was tested using tk and gC as
      representative early and late promoters, respectively. Nuclear extracts and
      phosphocellulose column fractions derived from nuclear extracts were able to
      reconstitute basal and ICP4-activated transcription of both promoters in vitro.
      When examining the contribution of the general transcription factors on the
      ability of ICP4 to activate transcription, the fraction containing the general
      transcription factor TFIIA was not essential for ICP4 activation of the gC
      promoter, but it was required for efficient activation of the tk promoter. The
      addition of recombinant TFIIA restored the ability of ICP4 to efficiently
      activate the tk promoter, but it had no net effect on activation of the gC
      promoter. The dispensability of TFIIA for ICP4 activation of the gC promoter
      required an intact INR element. In addition, microarray and Northern blot
      analysis indicated that TFIIA abundance may be reduced at late times of
      infection. This decrease in TFIIA expression during infection and its
      dispensability for activation of late but not early genes suggest one of possibly
      many mechanisms for the transition from viral early to late gene expression.

PMID- 15163712
TI  - Early detection of a two-long-terminal-repeat junction molecule in the cytoplasm
      of recombinant murine leukemia virus-infected cells.
AB  - We showed that a U5-U3 junction was reproducibly detected by a PCR assay as early
      as 1 to 2 h postinfection with a DNase-treated murine leukemia virus (MLV)
      containing supernatant in aphidicolin-arrested NIH 3T3 cells, as well as in
      nonarrested cells. Such detection is azidothymidine sensitive and corresponded to
      neosynthesized products of the reverse transcriptase. This observation was
      confirmed in two additional human cell lines, TE671 and ARPE-19. Using cell
      fractionation combined with careful controls, we found that a two-long-terminal
      repeat (two-LTR) junction molecule was detectable in the cytoplasm as early as 2
      h post virus entry. Altogether, our data indicated that the neosynthesized
      retroviral DNA led to the early formation of structures including true two-LTR
      junctions in the cytoplasm of MLV-infected cells. Thus, the classical assumption
      that two-LTR circles are a mitosis-dependent dead-end product accumulating in the
      nucleus must be reconsidered. MLV-derived products containing a two-LTR junction
      can no longer be used as an exclusive surrogate for the preintegration complex
      nuclear translocation event.

PMID- 15163711
TI  - Involvement of glutathione as a mechanism of indirect protection against
      spontaneous ex vivo apoptosis associated with bovine leukemia virus.
AB  - Viruses have developed strategies to counteract the apoptotic response of the
      infected host cells. Modulation of apoptosis is also thought to be a major
      component of viral persistence and progression to leukemia induced by
      retroviruses like human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia
      virus (BLV). Here, we analyzed the mechanism of ex vivo apoptosis occurring after
      isolation of peripheral blood mononuclear cells from BLV-infected sheep. We show
      that spontaneous apoptosis of ovine B lymphocytes requires at least in part a
      caspase 8-dependent pathway regardless of viral infection. Cell death is
      independent of cytotoxic response and does not involve the tumor necrosis factor
      alpha/NF-kappaB/nitric oxide synthase/cyclooxygenase pathway. In contrast,
      pharmaceutical depletion of reduced glutathione (namely, gamma-glutamyl-l
      cysteinyl-glycine [GSH]) by using ethacrynic acid or 1-pyrrolidinecarbodithioic
      acid specifically reverts inhibition of spontaneous apoptosis conferred
      indirectly by protective BLV-conditioned media; inversely, exogenously provided
      membrane-permeable GSH-monoethyl ester restores cell viability in B lymphocytes
      of BLV-infected sheep. Most importantly, intracellular GSH levels correlate with
      virus-associated protection against apoptosis but not with general inhibition of
      cell death induced by polyclonal activators, such as phorbol esters and
      ionomycin. Finally, inhibition of apoptosis does not correlate with the
      activities of GSH peroxidase and GSH reductase. In summary, our data fit into a
      model in which modulation of the glutathione system is a key event involved in
      indirect inhibition of apoptosis associated with BLV. These observations could
      have decisive effects during therapeutic treatment of delta-retroviral
      pathogenesis.

PMID- 15163713
TI  - Common structure of rare replication-deficient E1-positive particles in
      adenoviral vector batches.
AB  - The use of the PER.C6 adenovirus packaging cell line in combination with a
      designated vector plasmid system, whereby the cell line and vector with E1
      deleted have no sequence overlap, eliminates the generation of replication
      competent adenovirus during vector production. However, we have found cytopathic
      effect (CPE)-inducing particles in 2 out of more than 40 large-scale
      manufacturing lots produced in PER.C6 cells. The CPE inducer was detected at a
      frequency of 1 event in 7.5 x 10(12) vector particles. Despite amplification, it
      was not readily purified, indicating that the agent itself is replication
      deficient and requires the parental recombinant adenovirus serotype 5 (rAd5)
      vector for replication and packaging. Therefore, we designated the agent as a
      helper-dependent E1-positive region containing viral particle (HDEP). Here, we
      report the molecular structure of the HDEP genome, revealing an Ad comprised of
      E1 sequences derived from PER.C6 cells flanked by inverted terminal repeat,
      packaging signal, and transgene sequences. These sequences form a palindromic
      structure devoid of E2, E3, E4, and late genes. Since only 5 bp were shared
      between E1 sequences in the PER.C6 genome and viral vector sequences, the data
      strongly suggested that insertion of genomic DNA into an adenoviral genome had
      occurred essentially via nonhomologous recombination. HDEPs have been found in
      unrelated virus batches and appear to share a common structure that may explain
      their mechanism of generation. This finding allowed development of an HDEP assay
      to screen batches of rAd5 produced on the PER.C6 cell line and resulted in
      detection of seven HDEP agents from four different transgene-virus vector
      constructs in separate batches of Ad.

PMID- 15163714
TI  - Identification of synthetic endothelial cell-specific promoters by use of a high
      throughput screen.
AB  - Transcriptional targeting is a desirable property for many gene transfer
      applications. Because endothelial cells line most blood vessels, they are
      attractive candidates for the introduction of therapeutic gene products. As a
      proof-of-concept study, we attempted to identify a synthetic, endothelial cell
      specific promoter by use of a high-throughput screen involving self-inactivating
      (SIN) human immunodeficiency virus type 1 (HIV-1)-based vectors. Select duplex
      oligodeoxynucleotides recognized by transcription factors and located 5' of
      endothelial cell-specific mRNA transcripts were randomly ligated and cloned
      upstream of a minimal ICAM-2 promoter driving enhanced green fluorescent protein
      (eGFP) in a SIN HIV-1-based vector. Vesicular stomatitis virus G protein
      pseudotyped particles were prepared from a library of >10(6) vector recombinants
      and used to transduce an endothelial cell line. The highest eGFP expressers were
      repeatedly sorted, and the synthetic promoters were recovered and retested by a
      luciferase reporter. Several promoters were active and specific to endothelial
      cells of varied species, with high selectivity indexes and inducibility under
      hypoxia-mimetic conditions. One in particular was then introduced back into a SIN
      HIV-1-based vector to confirm its endothelial cell activity and specificity. This
      study suggests that SIN vectors may be used in a high-throughput manner to
      identify tissue-specific promoters of high activity, with potential applications
      for both transcriptional targeting and gene transfer.

PMID- 15163716
TI  - The P domain of norovirus capsid protein forms dimer and binds to histo-blood
      group antigen receptors.
AB  - Noroviruses (NVs) are the most important pathogen of epidemic nonbacterial
      gastroenteritis. The recent finding that NVs recognize human histo-blood group
      antigens (HBGAs) as receptors provided a new approach to study the pathogenesis
      of NVs. Using computational and site-directed mutagenesis approaches, our
      investigators previously identified a plausible binding pocket in the P domain of
      the NV capsids. In this study, we further characterize the role of the P domain
      in the interaction with human HBGA receptors using three NV strains representing
      three binding patterns. Our results show that the isolated P domain, although it
      did not form virus-like particles (VLPs), formed dimers, and the dimers bound
      HBGAs with the same patterns as those of the intact viral capsids. In contrast,
      the S domain, which formed small, thin-layer VLPs, did not bind A, B, or H HBGAs.
      A chimera containing the S domain of VA387 and the P domain of MOH revealed a
      binding pattern of the P donor strain (MOH). Deletion experiments revealed that
      an intact P domain is necessary for receptor binding. The P domain dimers are
      stable over a broad range of pH (2 to 11) or under strong denaturing conditions.
      Taken together, our results suggest that the P domain of NV contains essential
      elements for strain-specific binding to receptors. Further study of the P domain
      will provide useful information about the virus-receptor interaction. The high
      yield and easy production of the recombinant P protein in the Escherichia coli
      expression system will provide a simple approach to this goal.

PMID- 15163715
TI  - Insertion of host-derived costimulatory molecules CD80 (B7.1) and CD86 (B7.2)
      into human immunodeficiency virus type 1 affects the virus life cycle.
AB  - Human immunodeficiency virus type 1 (HIV-1) carries virus-encoded and host
      derived proteins. Recent advances in the functional characterization of host
      molecules inserted into mature virus particles have revealed that HIV-1 biology
      is influenced by the acquisition of host cell membrane components. The CD28/B7
      receptor/ligand system is considered one of the fundamental elements of the
      normal immune response. Two major cell types that harbor HIV-1 in vivo, i.e.,
      monocytes/macrophages and CD4+ T cells, express the costimulatory molecules CD80
      (B7.1) and CD86 (B7.2). We investigated whether CD80 and CD86 are efficiently
      acquired by HIV-1, and if so, whether these host-encoded molecules can contribute
      to the virus life cycle. Here we provide the first evidence that the insertion of
      CD80 and CD86 into HIV-1 increases virus infectivity by facilitating the
      attachment and entry process due to interactions with their two natural ligands,
      CD28 and CTLA-4. Moreover, we demonstrate that NF-kappaB is induced by CD80- and
      CD86-bearing virions when they are combined with the engagement of the T-cell
      receptor/CD3 complex, an event that is inhibited upon surface expression of CTLA
      4. Finally, both CD80 and CD86 were found to be efficiently incorporated into R5-
      and X4-tropic field strains of HIV-1 expanded in cytokine-treated macrophages.
      Thus, besides direct interactions between the virus envelope glycoproteins and
      cell surface constituents, such as CD4 and some specific chemokine coreceptors,
      HIV-1 may attach to target cells via interactions between cell-derived molecules
      incorporated into virions and their natural ligands. These findings support the
      theory that HIV-1-associated host proteins alter virus-host dynamics.

PMID- 15163718
TI  - A novel cis-acting element facilitates minus-strand DNA synthesis during reverse
      transcription of the hepatitis B virus genome.
AB  - Hepadnaviruses replicate through reverse transcription of an RNA pregenome,
      resulting in a relaxed circular DNA genome. The first 3 or 4 nucleotides (nt) of
      minus-strand DNA are synthesized by the use of a bulge in a stem-loop structure
      near the 5' end of the pregenome as a template. This primer is then transferred
      to a complementary UUCA motif, termed an acceptor, within DR1* near the 3' end of
      the viral pregenome via 4-nt homology, and it resumes minus-strand DNA synthesis:
      this process is termed minus-strand transfer or primer translocation. Aside from
      the sequence identity of the donor and acceptor, little is known about the
      sequence elements contributing to minus-strand transfer. Here we report a novel
      cis-acting element, termed the beta5 region (28 nt in length), located 20 nt
      upstream of DR1*, that facilitates minus-strand DNA synthesis. The deletion or
      inversion of the sequence including the beta5 region diminished minus-strand DNA
      synthesis initiated at DR1*. Furthermore, the insertion of the beta5 region into
      its own position in a mutant in which the sequences including the beta5 region
      were replaced restored minus-strand DNA synthesis at DR1*. We speculate that the
      beta5 region facilitates minus-strand transfer, possibly by bringing the acceptor
      site in proximity to the donor site via base pairing or by interacting with
      protein factors involved in this process.

PMID- 15163717
TI  - Molecular analysis of the protease-resistant prion protein in scrapie and bovine
      spongiform encephalopathy transmitted to ovine transgenic and wild-type mice.
AB  - The existence of different strains of infectious agents involved in scrapie, a
      transmissible spongiform encephalopathy (TSE) of sheep and goats, remains poorly
      explained. These strains can, however, be differentiated by characteristics of
      the disease in mice and also by the molecular features of the protease-resistant
      prion protein (PrP(res)) that accumulates into the infected tissues. For further
      analysis, we first transmitted the disease from brain samples of TSE-infected
      sheep to ovine transgenic [Tg(OvPrP4)] and to wild-type (C57BL/6) mice. We show
      that, as in sheep, molecular differences of PrP(res) detected by Western blotting
      can differentiate, in both ovine transgenic and wild-type mice, infection by the
      bovine spongiform encephalopathy (BSE) agent from most scrapie sources.
      Similarities of an experimental scrapie isolate (CH1641) with BSE were also
      likewise found following transmission in ovine transgenic mice. Secondly, we
      transmitted the disease to ovine transgenic mice by inoculation of brain samples
      of wild-type mice infected with different experimental scrapie strains (C506M3,
      87V, 79A, and Chandler) or with BSE. Features of these strains in ovine
      transgenic mice were reminiscent of those previously described for wild-type
      mice, by both ratios and by molecular masses of the different PrP(res)
      glycoforms. Moreover, these studies revealed the diversity of scrapie strains and
      their differences with BSE according to labeling by a monoclonal antibody (P4).
      These data, in an experimental model expressing the prion protein of the host of
      natural scrapie, further suggest a genuine diversity of TSE infectious agents and
      emphasize its linkage to the molecular features of the abnormal prion protein.

PMID- 15163719
TI  - Mutational analysis of the influenza virus cRNA promoter and identification of
      nucleotides critical for replication.
AB  - Replication of the influenza A virus virion RNA (vRNA) requires the synthesis of
      full-length cRNA, which in turn is used as a template for the synthesis of more
      vRNA. A "corkscrew" secondary-structure model of the cRNA promoter has been
      proposed recently. However the data in support of that model were indirect, since
      they were derived from measurement, by use of a chloramphenicol acetyltransferase
      (CAT) reporter in 293T cells, of mRNA levels from a modified cRNA promoter rather
      than the authentic cRNA promoter found in influenza A viruses. Here we measured
      steady-state cRNA and vRNA levels from a CAT reporter in 293T cells, directly
      measuring the replication of the authentic influenza A virus wild-type cRNA
      promoter. We found that (i) base pairing between the 5' and 3' ends and (ii) base
      pairing in the stems of both the 5' and 3' hairpin loops of the cRNA promoter
      were required for in vivo replication. Moreover, nucleotides in the tetraloop at
      positions 4, 5, and 7 and nucleotides forming the 2-9 base pair of the 3' hairpin
      loop were crucial for promoter activity in vivo. However, the 3' hairpin loop was
      not required for polymerase binding in vitro. Overall, our results suggest that
      the corkscrew secondary-structure model is required for authentic cRNA promoter
      activity in vivo, although the precise role of the 3' hairpin loop remains
      unknown.

PMID- 15163720
TI  - RNA recombination in vivo in the absence of viral replication.
AB  - To study fundamental aspects of RNA recombination, an in vivo RNA recombination
      system was established. This system allowed the efficient generation of
      recombinant cytopathogenic pestiviruses after transfection of synthetic,
      nonreplicatable, subgenomic transcripts in cells infected with a replicating
      noncytopathogenic virus. Studies addressing the interplay between RNA
      recombination and replication revealed that cotransfection of noninfected cells
      with various pairs of nonreplicatable RNA derivatives also led to the emergence
      of recombinant viral genomes. Remarkably, homologous and nonhomologous
      recombination occurred between two overlapping transcripts, each lacking
      different essential parts of the viral RNA-dependent RNA polymerase (RdRp) gene.
      Apart from the generally accepted viral replicative copy choice recombination,
      our results prove the existence of a viral RdRp-independent mechanism of RNA
      recombination that occurs in vivo. It appears likely that such a mechanism not
      only contributes to the evolution of RNA viruses but also leads to the generation
      of recombinant cellular RNAs.

PMID- 15163721
TI  - Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1
      contributes to inhibition of the interferon signaling pathway.
AB  - We showed previously that herpes simplex virus type 1 (HSV-1) suppresses the
      interferon (IFN) signaling pathway during the early infection stage in the human
      amnion cell line FL. HSV-1 inhibits the IFN-induced phosphorylation of Janus
      kinases (JAK) in infected FL cells. In the present study, we showed that the
      suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the
      JAK/STAT pathway, is rapidly induced in FL cells after HSV-1 infection. Maximal
      levels of SOCS3 protein were detected at around 1 to 2 h after infection. This is
      consistent with the occurrence of HSV-1-mediated inhibition of IFN-induced JAK
      phosphorylation. The HSV-1 wild-type strain VR3 induced SOCS3 more efficiently
      than did mutants that are defective in UL41 or UL13 and that are hyperresponsive
      to IFN. Induction of the IRF-7 protein and transcriptional activation of IFN
      alpha4, which occur in a JAK/STAT pathway-dependent manner, were poorly induced
      by VR3 but efficiently induced by the mutant viruses. In contrast,
      phosphorylation of IRF-3 and transcriptional activation of IFN-beta, which are
      JAK/STAT pathway-independent process, were equally well induced by the wild-type
      strain and the mutants. In conclusion, the SOCS3 protein appears to be mainly
      responsible for the suppression of IFN signaling and IFN production that occurs
      during HSV-1 infection.

PMID- 15163722
TI  - Nef stimulates human immunodeficiency virus type 1 replication in primary T cells
      by enhancing virion-associated gp120 levels: coreceptor-dependent requirement for
      Nef in viral replication.
AB  - The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) replication
      through an unknown mechanism. We and others have previously reported that
      efficient HIV-1 replication in activated primary CD4(+) T cells depends on the
      ability of Nef to downregulate CD4 from the cell surface. Here we demonstrate
      that Nef greatly enhances the infectivity of HIV-1 particles produced in primary
      T cells. Nef-defective HIV-1 particles contained significantly reduced quantities
      of gp120 on their surface; however, Nef did not affect the levels of virion
      associated gp41, indicating that Nef indirectly stabilizes the association of
      gp120 with gp41. Surprisingly, Nef was not required for efficient replication of
      viruses that use CCR5 for entry, nor did Nef influence the infectivity or gp120
      content of these virions. Nef also inhibited the incorporation of CD4 into HIV-1
      particles released from primary T cells. We propose that Nef, by downregulating
      cell surface CD4, enhances HIV-1 replication by inhibiting CD4-induced
      dissociation of gp120 from gp41. The preferential requirement for Nef in the
      replication of X4-tropic HIV-1 suggests that the ability of Nef to downregulate
      CD4 may be most important at later stages of disease when X4-tropic viruses
      emerge.

PMID- 15163724
TI  - PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates
      variably sized pores in planar lipid membranes.
AB  - A frameshifted region of the influenza A virus PB1 gene encodes a novel protein,
      termed PB1-F2, a mitochondrial protein that can induce cell death. Many
      proapoptotic proteins are believed to act at the mitochondrial outer membrane to
      form an apoptotic pore with lipids. We studied the interaction of isolated,
      synthetic PB1-F2 (sPB1-F2) peptide with planar phospholipid bilayer membranes.
      The presence of nanomolar concentrations of peptide in the bathing solution
      induced a transmembrane conductance that increased in a potential-dependent
      manner. Positive potential on the side of protein addition resulted in a
      severalfold increase in the rate of change of membrane conductance. sPB1-F2
      treated membranes became permeable to monovalent cations, chloride, and to a
      lesser extent, divalent ions. Despite various experimental conditions, we did not
      detect the distinctive conductance levels typical of large, stable pores, protein
      channels, or even pores that are partially proteinaceous. Rather, membrane
      conductance induced by sPB1-F2 fluctuated and visited almost all conductance
      values. sPB1-F2 also dramatically decreased bilayer stability in an electric
      field, consistent with a decrease in the line tension of a lipidic pore. Since
      similar membrane-destabilizing profiles are seen with proapoptotic proteins
      (e.g., Bax) and the cytoplasmic helix of human immunodeficiency virus gp41, we
      suggest that the basis for sPB1-F2-induced cell death may be the permeabilization
      and destabilization of mitochondrial membranes, leading to macromolecular leakage
      and apoptosis.

PMID- 15163723
TI  - A chimeric porcine circovirus (PCV) with the immunogenic capsid gene of the
      pathogenic PCV type 2 (PCV2) cloned into the genomic backbone of the
      nonpathogenic PCV1 induces protective immunity against PCV2 infection in pigs.
AB  - Porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic
      wasting syndrome in pigs, whereas PCV1 is nonpathogenic. We previously
      demonstrated that a chimeric PCV1-2 virus (with the immunogenic capsid gene of
      PCV2 cloned into the backbone of PCV1) induces an antibody response to the PCV2
      capsid protein and is attenuated in pigs. Here, we report that the attenuated
      chimeric PCV1-2 induces protective immunity to wild-type PCV2 challenge in pigs.
      A total of 48 specific-pathogen-free piglets were randomly and equally assigned
      to four groups of 12 pigs each. Pigs in group 1 were vaccinated by intramuscular
      injection with 200 microg of the chimeric PCV1-2 infectious DNA clone. Pigs in
      group 2 were vaccinated by intralymphoid injection with 200 microg of a chimeric
      PCV1-2 infectious DNA clone. Pigs in group 3 were vaccinated by intramuscular
      injection with 10(3.5) 50% tissue culture infective doses (TCID(50)) of the
      chimeric PCV1-2 live virus. Pigs in group 4 were not vaccinated and served as
      controls. By 42 days postvaccination (DPV), the majority of pigs had
      seroconverted to PCV2 capsid antibody. At 42 DPV, all pigs were challenged
      intranasally and intramuscularly with 2 x 10(4.5) TCID(50) of a wild-type
      pathogenic PCV2 virus. By 21 days postchallenge (DPC), 9 out of the 12 group 4
      pigs were viremic for PCV2. Vaccinated animals in groups 1 to 3 had no detectable
      PCV2 viremia after challenge. At 21 DPC the lymph nodes in the nonvaccinated pigs
      were larger (P < 0.05) than those of vaccinated pigs. The PCV2 genomic copy loads
      in lymph nodes were reduced (P < 0.0001) in vaccinated pigs. Moderate amounts of
      PCV2 antigen were detected in most lymphoid tissues of nonvaccinated pigs but in
      only 1 of 36 vaccinated pigs. Mild-to-severe lymphoid depletion and histiocytic
      replacement were detected in lymphoid tissues in the majority of nonvaccinated
      group 4 pigs but in only a few vaccinated group 1 to 3 pigs. The data from this
      study indicated that when given intramuscularly in pigs, the attenuated chimeric
      PCV1-2 live virus, as well as the chimeric PCV1-2 infectious DNA clone, induces
      protective immunity against PCV2 infection and could potentially serve as an
      effective vaccine.

PMID- 15163727
TI  - Role of the I7 protein in proteolytic processing of vaccinia virus membrane and
      core components.
AB  - Certain core and membrane proteins of vaccinia virus undergo proteolytic cleavage
      at consensus AG/X sites. The processing of core proteins is coupled to
      morphogenesis and is inhibited by the drug rifampin, whereas processing of the
      A17 membrane protein occurs at an earlier stage of assembly and is unaffected by
      the drug. A temperature-sensitive mutant with a lesion in the I7L gene exhibits
      blocks in morphogenesis and in cleavage of core proteins. We found that the
      mutant also failed to cleave the A17 membrane protein. To further investigate the
      role of the putative I7 protease, we constructed a conditional lethal mutant in
      which the I7L gene was regulated by the Escherichia coli lac repressor. In the
      absence of an inducer, the synthesis of I7 was repressed, proteolytic processing
      of the A17 membrane protein and the L4 core protein was inhibited, and virus
      morphogenesis was blocked. Under these conditions, expression of the wild-type I7
      protein in trans restored protein processing. In contrast, rescue did not occur
      when the putative protease active site residue histidine 241 or cysteine 328 of
      I7 was converted to alanine. The mutation of an authentic AG/A and an alternative
      AG/S motif of L4 prevented substrate cleavage. Similarly, when AG/X sites of A17
      were mutated, I7-induced cleavages at the N and C termini failed to occur. In
      conclusion, we provide evidence that I7 is a viral protease that is required for
      AG/X-specific cleavages of viral membrane and core proteins, which occur at early
      and late stages of virus assembly, respectively.

PMID- 15163726
TI  - Identification of a protective CD4+ T-cell epitope in p15gag of Friend murine
      leukemia virus and role of the MA protein targeting the plasma membrane in
      immunogenicity.
AB  - Recent studies have demonstrated an essential role of Gag-specific CD4+ T-cell
      responses for viral control in individuals infected with human immunodeficiency
      virus type 1. However, little is known about epitope specificities and functional
      roles of the Gag-specific helper T-cell responses in terms of vaccine-induced
      protection against a pathogenic retroviral challenge. We have previously
      demonstrated that immunization with Friend murine leukemia virus (F-MuLV) Gag
      proteins protects mice against the fatal Friend retrovirus (FV) infection. We
      report here the structure of a protective T helper cell (Th) epitope,
      (I)VTWEAIAVDPPP, identified in the p15 (MA) region of F-MuLV Gag. In mice
      immunized with the Th epitope-harboring peptide or a vaccinia virus-expressed
      native full-length MA protein, FV-induced early splenomegaly regressed rapidly.
      In these mice, FV-infected cells were eliminated within 4 weeks and the
      production of virus-neutralizing antibodies was induced rapidly after FV
      challenge, resulting in strong protection against the virus infection.
      Interestingly, mice immunized with the whole MA mounted strong CD4+ T-cell
      responses to the identified Th epitope, whereas mice immunized with mutant MA
      proteins that were not bound to the plasma membrane failed to mount efficient
      CD4+ T-cell responses, despite the presence of the Th epitope. These mutant MA
      proteins also failed to induce strong protection against FV challenge. These data
      indicate the importance of the properly processible MA molecule for CD4+ T-cell
      priming and for the resultant induction of an effective immune response against
      retrovirus infections.

PMID- 15163725
TI  - Proteolytic cleavage of the catalytic subunit of DNA-dependent protein kinase
      during poliovirus infection.
AB  - DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase that has
      critical roles in DNA double-strand break repair, as well as B- and T-cell
      antigen receptor rearrangement. The DNA-PK enzyme consists of the Ku regulatory
      subunit and a 450-kDa catalytic subunit termed DNA-PK(CS). Both of these subunits
      are autoantigens associated with connective tissue diseases such as systemic
      lupus erythematosus (SLE) and scleroderma. In this report, we show that DNA
      PK(CS) is cleaved during poliovirus infection of HeLa cells. Cleavage was visible
      as early as 1.5 h postinfection (hpi) and resulted in an approximately 40%
      reduction in the levels of native protein by 5.5 hpi. Consistent with this
      observation, the activity of the DNA-PK(CS) enzyme was also reduced during viral
      infection, as determined by immunoprecipitation kinase assays. Although it has
      previously been shown that DNA-PK(CS) is a substrate of caspase-3 in vitro, the
      protein was still cleaved during poliovirus infection of the caspase-3-deficient
      MCF-7 cell line. Cleavage was not prevented by infection in the presence of a
      soluble caspase inhibitor, suggesting that cleavage in vivo was independent of
      host caspase activation. DNA-PK(CS) is directly cleaved by a picornaviral 2A
      protease in vitro, producing a fragment similar in size to the cleavage product
      observed in vivo. Taken together, our results indicate that DNA-PK(CS) is cleaved
      by the 2A protease during poliovirus infection. Proteolytic cleavage of DNA
      PK(CS) during poliovirus infection may contribute to inhibition of host immune
      responses. Furthermore, cleavage of autoantigens by viral proteases may target
      these proteins for the autoimmune response by generating novel, or
      "immunocryptic," protein fragments.

PMID- 15163728
TI  - Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies
      inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer
      in the brain.
AB  - Epidemiological studies report that 80% of the population maintains antibodies
      (Ab) to wild-type (wt) adeno-associated virus type 2 (AAV2), with 30% expressing
      neutralizing Ab (NAb). The blood-brain barrier (BBB) provides limited immune
      privilege to brain parenchyma, and the immune response to recombinant AAV (rAAV)
      administration in the brain of a naive animal is minimal. However, central
      nervous system transduction in preimmunized animals remains unstudied. Vector
      administration may disrupt the BBB sufficiently to promote an immune response in
      a previously immunized animal. We tested the hypothesis that intracerebral rAAV
      administration and readministration would not be affected by the presence of
      circulating Ab to wt AAV2. Rats peripherally immunized with live wt AAV2 and
      naive controls were tested with single intrastriatal injections of rAAV2 encoding
      human glial cell line-derived neurotrophic factor (GDNF) or green fluorescent
      protein (GFP). Striatal readministration of rAAV2-GDNF was also tested in
      preimmunized and naive rats. Finally, serotype specificity of the immunization
      against wt AAV2 was examined by single injections of rAAV5-GFP. Preimmunization
      resulted in high levels of circulating NAb and prevented transduction by rAAV2 as
      assessed by striatal GDNF levels. rAAV2-GFP striatal transduction was also
      prevented by immunization, while rAAV5-GFP-mediated transduction, as assessed by
      stereological cell counting, was unaffected. Additionally, inflammatory markers
      were present in those animals that received repeated administrations of rAAV2,
      including markers of a cell-mediated immune response and cytotoxic damage. A live
      virus immunization protocol generated the circulating anti-wt-AAV Ab seen in this
      experiment, while human titers are commonly acquired via natural infection.
      Regardless, the data show that the presence of high levels of NAb against wt AAV
      can reduce rAAV-mediated transduction in the brain and should be accounted for in
      future experiments utilizing this vector.

PMID- 15163729
TI  - Novel nuclear herniations induced by nuclear localization of a viral protein.
AB  - A common consequence of viral infection is perturbation of host cell nuclear
      functions. For cytoplasmically replicating viruses, this process may require
      regulated transport of specific viral proteins into the nucleus. Here, we
      describe a novel form of virus-induced perturbation of host cell nuclear
      structures. Active signal-mediated nuclear import of the reovirus sigma1s protein
      results in redistribution of nuclear pore complexes and nuclear lamins and
      formation of nuclear herniations. These herniations represent a previously
      undescribed mechanism by which cytoplasmic viral infection can perturb nuclear
      architecture and induce cytopathic effects, which ultimately lead to disease
      pathogenesis in the infected host.

PMID- 15163730
TI  - Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C
      virus core protein.
AB  - Hepatitis C virus (HCV) core protein is suggested to localize to the endoplasmic
      reticulum (ER) through a C-terminal hydrophobic region that acts as a membrane
      anchor for core protein and as a signal sequence for E1 protein. The signal
      sequence of core protein is further processed by signal peptide peptidase (SPP).
      We examined the regions of core protein responsible for ER retention and
      processing by SPP. Analysis of the intracellular localization of deletion mutants
      of HCV core protein revealed that not only the C-terminal signal-anchor sequence
      but also an upstream hydrophobic region from amino acid 128 to 151 is required
      for ER retention of core protein. Precise mutation analyses indicated that
      replacement of Leu(139), Val(140), and Leu(144) of core protein by Ala inhibited
      processing by SPP, but cleavage at the core-E1 junction by signal peptidase was
      maintained. Additionally, the processed E1 protein was translocated into the ER
      and glycosylated with high-mannose oligosaccharides. Core protein derived from
      the mutants was translocated into the nucleus in spite of the presence of the
      unprocessed C-terminal signal-anchor sequence. Although the direct association of
      core protein with a wild-type SPP was not observed, expression of a loss-of
      function SPP mutant inhibited cleavage of the signal sequence by SPP and
      coimmunoprecipitation with unprocessed core protein. These results indicate that
      Leu(139), Val(140), and Leu(144) in core protein play crucial roles in the ER
      retention and SPP cleavage of HCV core protein.

PMID- 15163731
TI  - Clades of Adeno-associated viruses are widely disseminated in human tissues.
AB  - The potential for using Adeno-associated virus (AAV) as a vector for human gene
      therapy has stimulated interest in the Dependovirus genus. Serologic data suggest
      that AAV infections are prevalent in humans, although analyses of viruses and
      viral sequences from clinical samples are extremely limited. Molecular techniques
      were used in this study to successfully detect endogenous AAV sequences in 18% of
      all human tissues screened, with the liver and bone marrow being the most
      predominant sites. Sequence characterization of rescued AAV DNAs indicated a
      diverse array of molecular forms which segregate into clades whose members share
      functional and serologic similarities. One of the most predominant human clades
      is a hybrid of two previously described AAV serotypes, while another clade was
      found in humans and several species of nonhuman primates, suggesting a cross
      species transmission of this virus. These data provide important information
      regarding the biology of parvoviruses in humans and their use as gene therapy
      vectors.

PMID- 15163732
TI  - Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is dispensable for
      virus entry.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is considered the etiologic agent
      of Kaposi's sarcoma and several lymphoproliferative disorders. Recently, the KSHV
      genome was cloned into a bacterial artificial chromosome and used to construct a
      recombinant KSHV carrying a deletion of the viral interferon regulatory factor
      gene (F. C. Zhou, Y. J. Zhang, J. H. Deng, X. P. Wang, H. Y. Pan, E. Hettler, and
      S. J. Gao, J. Virol. 76:6185-6196, 2002). The K8.1 glycoprotein is a structural
      component of the KSHV particle and is thought to facilitate virus entry by
      binding to heparan sulfate moieties on cell surfaces. To further address the role
      of K8.1 in virus infectivity, a K8.1-null recombinant virus (BAC36DeltaK8.1) was
      constructed by deletion of most of the K8.1 open reading frame and insertion of a
      kanamycin resistance gene cassette within the K8.1 gene. Southern blotting and
      diagnostic PCR confirmed the presence of the engineered K8.1 gene deletion.
      Transfection of the wild-type genome (BAC36) and mutant genome (BAC36DeltaK8.1)
      DNAs into 293 cells in the presence or absence of the complementing plasmid
      (pCDNAK8.1A), transiently expressing the K8.1A gene, produced infectious virions
      in the supernatants of transfected cells. These results demonstrated that the
      K8.1 glycoprotein is not required for KSHV entry into 293 cells.

PMID- 15163733
TI  - High beta-chemokine expression levels in lymphoid tissues of simian/human
      immunodeficiency virus 89.6-vaccinated rhesus macaques are associated with
      uncontrolled replication of simian immunodeficiency virus challenge inoculum.
AB  - Viral suppression by noncytolytic CD8+ T cells, in addition to that by classic
      antiviral CD8+ cytotoxic T lymphocytes, has been described for human
      immunodeficiency virus and simian immunodeficiency virus (SIV) infections.
      However, the role of soluble effector molecules, especially beta-chemokines, in
      antiviral immunity is still controversial. In an attenuated vaccine model,
      approximately 60% of animals immunized with simian/human immunodeficiency virus
      (SHIV) 89.6 and then challenged intravaginally with SIVmac239 controlled viral
      replication (viral RNA level in plasma, <10(4) copies/ml) and were considered
      protected (K. Abel, L. Compton, T. Rourke, D. Montefiori, D. Lu, K. Rothaeusler,
      L. Fritts, K. Bost, and C. J. Miller, J. Virol. 77:3099-3118, 2003). To determine
      the in vivo importance of beta-chemokine secretion and CD8+-T-cell proliferation
      in the control of viral replication in this vaccine model, we examined the
      relationship between viral RNA levels in the axillary and genital lymph nodes of
      vaccinated, protected (n = 20) and vaccinated, unprotected (n = 11) monkeys by
      measuring beta-chemokine mRNA levels and protein expression, the frequency of
      CD8+ T cells expressing beta-chemokines, and the extent of CD8+-T-cell
      proliferation. Tissues from uninfected (n = 3) and unvaccinated, SIVmac239
      infected (n = 9) monkeys served as controls. Axillary and genital lymph nodes
      from unvaccinated and vaccinated, unprotected monkeys had significantly higher
      beta-chemokine mRNA expression levels and increased numbers of beta-chemokine
      positive cells than did vaccinated, protected animals. Furthermore, the lymph
      nodes of vaccinated, unprotected monkeys had significantly higher numbers of beta
      chemokine(+) CD8+ T cells than did vaccinated, protected monkeys. Lymph nodes
      from vaccinated, unprotected animals also had significantly more CD8+-T-cell
      proliferation and marked lymph node hyperplasia than the lymph nodes of
      vaccinated, protected monkeys. Thus, higher levels of virus replication were
      associated with increased beta-chemokine secretion and there is no evidence that
      beta-chemokines contributed to the SHIV89.6-mediated control of viral replication
      after intravaginal challenge with SIVmac239.

PMID- 15163734
TI  - Direct binding of hepatitis C virus core to gC1qR on CD4+ and CD8+ T cells leads
      to impaired activation of Lck and Akt.
AB  - Complement plays a pivotal role in the regulation of innate and adaptive
      immunity. It has been shown that the binding of C1q, a natural ligand of gC1qR,
      on T cells inhibits their proliferation. Here, we demonstrate that direct binding
      of the hepatitis C virus (HCV) core to gC1qR on T cells leads to impaired Lck/Akt
      activation and T-cell function. The HCV core associates with the surface of T
      cells specifically via gC1qR, as this binding is inhibited by the addition of
      either anti-gC1qR antibody or soluble gC1qR. The binding affinity constant of
      core protein for gC1qR, as determined by BIAcore analysis, is 3.8 x 10(-7) M. The
      specificity of the HCV core-gC1qR interaction is confirmed by reduced core
      binding on Molt-4 T cells treated with gC1qR-silencing small interfering RNA and
      enhanced core binding on GPC-16 guinea pig cells transfected with human gC1qR.
      Interestingly, gC1qR is expressed at higher levels on CD8(+) than on CD4(+) T
      cells, resulting in more severe core-induced suppression of the CD8(+)-T-cell
      population. Importantly, T-cell receptor-mediated activation of the Src kinases
      Lck and ZAP-70 but not Fyn and the phosphorylation of Akt are impaired by the HCV
      core, suggesting that it inhibits the very early events of T-cell activation.

PMID- 15163735
TI  - Phosphorylation of vesicular stomatitis virus phosphoprotein P is indispensable
      for virus growth.
AB  - The phosphoprotein (P) of vesicular stomatitis virus (VSV) is an essential
      subunit of the viral RNA-dependent RNA polymerase (RdRp) complex. It is
      phosphorylated at two different domains. Using defective interfering (DI) RNA or
      minigenomic RNA templates, we previously demonstrated that phosphorylation within
      the amino-terminal domain I is essential for transcription, whereas
      phosphorylation within the carboxy-terminal domain II is necessary for
      replication. For the present study, we examined the role of the phosphorylation
      of residues in these domains in the life cycle of VSV. Various mutant P coding
      sequences were inserted into a full-length cDNA clone of VSV, and the virus
      recovery, kinetics of growth, and mRNA and protein synthesis were examined. We
      observed that virus recovery was completely abolished when all three phosphate
      acceptor sites in domain I or both sites in domain II were replaced with alanine.
      Single or double mutations in domain I (with the exception of P60/64) or single
      mutations in domain II had no adverse effect on virus recovery. VSVP227, carrying
      alanine at position 227, showed reduced kinetics of virus growth but increased
      kinetics of viral mRNA synthesis in infected cells. More interestingly, this
      particular virus exhibited a significantly reduced cytopathic effects and
      apoptosis in infected cells, implying that P may be involved in these processes.
      Furthermore, we found that DI RNAs of different sizes were generated by high
      multiplicity passaging of various mutant VSVs, indicating that the viral RdRp may
      play a significant role in the process of DI particle generation. Taken together,
      our results suggest that the phosphorylation of residues in domains I and II of
      VSV P is indispensable for virus growth.

PMID- 15163736
TI  - Biodistribution of radioiodinated adenovirus fiber protein knob domain after
      intravenous injection in mice.
AB  - The knob domains from the fiber proteins of adenovirus serotypes 2 and 12 were
      labeled with radioiodine and then injected into the bloodstreams of mice. Knob
      proteins with functional binding sites for the coxsackie and adenovirus receptor
      (CAR) were cleared rapidly from the circulation, with radioactivity appearing
      predominantly in the stomach, while knob mutants unable to bind to CAR remained
      in the blood circulation for a prolonged period. The clearance of radiolabeled
      wild-type knob from the blood was slowed by coinjecting an excess of unlabeled
      wild-type knob protein. An earlier study showed that (99m)Tc-labeled knob protein
      with intact CAR-binding activity also cleared rapidly from the blood circulation
      of mice, with radioactivity accumulating predominantly in the liver (K. R. Zinn
      et al., Gene Ther. 5:798-808, 1998). Together these results suggest that rapid
      clearance of knob protein from the blood results from specific binding to CAR in
      the liver and that the bound knob then enters a degradative pathway. The elevated
      levels of radioiodine in the stomach observed in our experiments are consistent
      with deiodination of labeled knob by dehalogenases in hepatocyte microsomes and
      uptake of the resultant free radioiodine by Na/I symporters in the gastric
      mucosa. Although CAR has been shown to localize in tight junctions of polarized
      epithelial cells, where it functions in intercellular adhesion, the results of
      our study suggest that a subset of CAR molecules in the liver is highly
      accessible to ligands in the blood and able to rapidly deliver bound ligand to an
      intracellular degradative compartment.

PMID- 15163737
TI  - Characterization of two Autographa californica nucleopolyhedrovirus proteins,
      Ac145 and Ac150, which affect oral infectivity in a host-dependent manner.
AB  - The genome of the baculovirus Autographa californica nuclear polyhedrosis virus
      (AcMNPV) contains two homologues, orf145 and orf150, of the Heliothis armigera
      Entomopoxvirus (HaEPV) 11,000-kDa gene. Polyclonal antibodies raised against the
      Ac145 or Ac150 protein were utilized to demonstrate that they are expressed from
      late to very late times of infection and are within the nuclei of infected Sf-21
      cells. Transmission electron microscopy coupled with immunogold labeling of Ac145
      found this protein within the nucleus in areas of nucleocapsid assembly and
      maturation, along with some association with the enveloped bundles of virions
      within the developing occlusion bodies (OBs). Ac150 was found to be mainly
      associated with enveloped bundles of virions within OBs and also with those not
      yet occluded. Both Ac145 and Ac150 were found to be present in budded virus as
      well as OBs. Both orf145 and orf150 were deleted from the AcMNPV genome, singly
      or together, and these deletion mutants were assessed for oral infectivity both
      in Trichoplusia ni and Heliothis virescens larvae. Deletion of Ac145 led to a
      small but significant drop in infectivity (sixfold) compared to wild-type (wt)
      AcMNPV for T. ni but not for H. virescens. Deletion of Ac150 alone had no effect
      on infectivity of the virus for either host. However, deletion of both Ac145 and
      Ac150 gave a recombinant virus with a drastic (39-fold) reduction in infectivity
      compared to wt virus for H. virescens. Intrahemocoelic injection of budded virus
      from the double-deletion virus into H. virescens larvae is as infectious to this
      host as wt budded virus, indicating that Ac145 and Ac150 play a role in primary
      oral infection of AcMNPV, the extent of which is host dependent.

PMID- 15163738
TI  - MCP-1 and CCR2 contribute to non-lymphocyte-mediated brain disease induced by
      Fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral
      neuropathogenesis.
AB  - Virus infection of the central nervous system (CNS) often results in chemokine
      upregulation. Although often associated with lymphocyte recruitment, increased
      chemokine expression is also associated with non-lymphocyte-mediated CNS disease.
      In these instances, the effect of chemokine upregulation on neurological disease
      is unclear. In vitro, several chemokines including monocyte chemotactic protein 1
      (MCP-1) protect neurons from apoptosis. Therefore, in vivo, chemokine
      upregulation may be a protective host response to CNS damage. Alternatively,
      chemokines may contribute to pathogenesis by stimulating intrinsic brain cells or
      recruiting macrophages to the brain. To investigate these possibilities, we
      studied a neurovirulent retrovirus, Fr98, that induces severe non-lymphocyte
      mediated neurological disease and causes the upregulation of several chemokines
      that bind to chemokine receptors CCR2 and CCR5. Knockout mice deficient in CCR2
      had reduced susceptibility to Fr98 pathogenesis, with significantly fewer mice
      developing clinical disease than did wild-type controls. In contrast, no
      reduction in Fr98-induced disease was observed in CCR5 knockout mice. Thus,
      signaling through CCR2, but not CCR5, plays an important role in Fr98-mediated
      pathogenesis. Three ligands for CCR2 (MCP-1, MCP-3, and MCP-5) were upregulated
      during Fr98 infection of the brain. Antibody-blocking experiments demonstrated
      that MCP-1 was important for retrovirus-induced neurological disease. In situ
      hybridization analysis revealed that MCP-1 was expressed by glial fibrillary
      acidic protein-positive astrocytes. Thus, astrocytes, previously not thought to
      play an effector role in the disease process were found to contribute to
      pathogenesis through the production of MCP-1. This study also demonstrates that
      chemokines can mediate pathogenesis in the CNS in the absence of lymphocytic
      infiltrate and gives credence to the hypothesis that chemokine upregulation is a
      mechanism by which retroviruses such as human immunodeficiency virus induce
      neurological damage.

PMID- 15163740
TI  - Inter- and intragenus structural variations in caliciviruses and their functional
      implications.
AB  - The family Caliciviridae is divided into four genera and consists of single
      stranded RNA viruses with hosts ranging from humans to a wide variety of animals.
      Human caliciviruses are the major cause of outbreaks of acute nonbacterial
      gastroenteritis, whereas animal caliciviruses cause various host-dependent
      illnesses with a documented potential for zoonoses. To investigate inter- and
      intragenus structural variations and to provide a better understanding of the
      structural basis of host specificity and strain diversity, we performed
      structural studies of the recombinant capsid of Grimsby virus, the recombinant
      capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4),
      which are representative of the genera Norovirus (genogroup 2), Sapovirus, and
      Vesivirus, respectively. A comparative analysis of these structures was performed
      with that of the recombinant capsid of Norwalk virus, a prototype member of
      Norovirus genogroup 1. Although these capsids share a common architectural
      framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral
      lattice with a modular domain organization of the subunit consisting of a shell
      (S) domain and a protrusion (P) domain, they exhibit distinct differences. The
      distally located P2 subdomain of P shows the most prominent differences both in
      shape and in size, in accordance with the observed sequence variability. Another
      major difference is in the relative orientation between the S and P domains,
      particularly between those of noroviruses and other caliciviruses. Despite being
      a human pathogen, the Parkville virus capsid shows more structural similarity to
      SMSV4, an animal calicivirus, suggesting a closer relationship between
      sapoviruses and animal caliciviruses. These comparative structural studies of
      caliciviruses provide a functional rationale for the unique modular domain
      organization of the capsid protein with an embedded flexibility reminiscent of an
      antibody structure. The highly conserved S domain functions to provide an
      icosahedral scaffold; the hypervariable P2 subdomain may function as a
      replaceable module to confer host specificity and strain diversity; and the P1
      subdomain, located between S and P2, provides additional fine-tuning to position
      the P2 subdomain.

PMID- 15163739
TI  - Adenovirus protein VII condenses DNA, represses transcription, and associates
      with transcriptional activator E1A.
AB  - Adenovirus protein VII is the major protein component of the viral nucleoprotein
      core. It is highly basic, and an estimated 1070 copies associate with each viral
      genome, forming a tightly condensed DNA-protein complex. We have investigated DNA
      condensation, transcriptional repression, and specific protein binding by protein
      VII. Xenopus oocytes were microinjected with mRNA encoding HA-tagged protein VII
      and prepared for visualization of lampbrush chromosomes. Immunostaining revealed
      that protein VII associated in a uniform manner across entire chromosomes.
      Furthermore, the chromosomes were significantly condensed and transcriptionally
      silenced, as judged by the dramatic disappearance of transcription loops
      characteristic of lampbrush chromosomes. During infection, the protein VII-DNA
      complex may be the initial substrate for transcriptional activation by cellular
      factors and the viral E1A protein. To investigate this possibility, mRNAs
      encoding E1A and protein VII were comicroinjected into Xenopus oocytes.
      Interestingly, whereas E1A did not associate with chromosomes in the absence of
      protein VII, expression of both proteins together resulted in significant
      association of E1A with lampbrush chromosomes. Binding studies with proteins
      produced in bacteria or human cells or by in vitro translation showed that E1A
      and protein VII can interact in vitro. Structure-function analysis revealed that
      an N-terminal region of E1A is responsible for binding to protein VII. These
      studies define the in vivo functions of protein VII in DNA binding, condensation,
      and transcriptional repression and indicate a role in E1A-mediated
      transcriptional activation of viral genes.

PMID- 15163742
TI  - Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A
      oncoprotein.
AB  - The saimiri transforming protein (STP) oncogene of Herpesvirus saimiri subgroup A
      strain 11 (STP-A11) is not required for viral replication but is required for
      lymphoid cell immortalization in culture and lymphoma induction in primates. We
      previously showed that STP-A11 interacts with cellular Src kinase through its SH2
      binding motif and that this interaction elicits Src signal transduction. Here we
      demonstrate that STP-A11 interacts with signal transducer and activator of
      transcription 3 (Stat3) independently of Src association and that the amino
      terminal short proline-rich motif of STP-A11 and the central linker region of
      Stat3 are necessary for their interaction. STP-A11 formed a triple complex with
      Src kinase and Stat3 where Src kinase phosphorylated Stat3, resulting in the
      nuclear localization and transcriptional activation of Stat3. Consequently, the
      constitutively active Stat3 induced by STP-A11 elicited cellular signal
      transduction, which ultimately induced cell survival and proliferation upon serum
      deprivation. Furthermore, this activity was strongly correlated with the
      induction of Fos, cyclin D1, and Bcl-XL expression. These results demonstrate
      that STP-A11 independently targets two important cellular signaling molecules,
      Src and Stat3, and that these proteins cooperate efficiently to induce STP-A11
      mediated transformation.

PMID- 15163741
TI  - Cross-packaging of human immunodeficiency virus type 1 vector RNA by spleen
      necrosis virus proteins: construction of a new generation of spleen necrosis
      virus-derived retroviral vectors.
AB  - The ability of the nonlentiviral retrovirus spleen necrosis virus (SNV) to cross
      package the genomic RNA of the distantly related human immunodeficiency virus
      type 1 (HIV-1) and vice versa was analyzed. Such a model may allow us to further
      study HIV-1 replication and pathogenesis, as well as to develop safe gene therapy
      vectors. Our results suggest that SNV can cross-package HIV-1 genomic RNA but
      with lower efficiency than HIV-1 proteins. However, HIV-1-specific proteins were
      unable to cross-package SNV RNA. We also constructed SNV-based gag-pol chimeric
      variants by replacing the SNV integrase with the HIV-1 integrase, based on
      multiple sequence alignments and domain analyses. These analyses revealed that
      there are conserved domains in all retroviral integrase open reading frames
      (orf), despite the divergence in the primary sequences. The transcomplementation
      assays suggested that SNV proteins recognized one of the chimeric variants. This
      demonstrated that HIV-1 integrase is functional in the SNV gag-pol orf with a
      lower transduction efficiency, utilizing homologous (SNV) RNA, as well as the
      heterologous vector RNA of HIV-1. These findings suggest that homology in the
      conserved sequences of the integrase protein may not be fully competent in the
      replacement of protein(s) from one retrovirus to another, and there are likely
      several other factors involved in each of the steps related to replication,
      integration, and infection. However, further studies to dissect the gag-pol
      region will be critical for understanding the mechanisms involved in the cleavage
      of reverse transcriptase, RNase H, and integrase. These studies should provide
      further insight into the design and development of novel molecular approaches to
      block HIV-1 replication and to construct a new generation of SNV-based vectors.

PMID- 15163743
TI  - Membrane association of greasy grouper nervous necrosis virus protein A and
      characterization of its mitochondrial localization targeting signal.
AB  - Localization of RNA replication to intracellular membranes is a universal feature
      of positive-strand RNA viruses. The betanodavirus greasy grouper (Epinephelus
      tauvina) nervous necrosis virus (GGNNV) is a positive-RNA virus with one of the
      smallest genomes among RNA viruses replicating in fish cells. To understand the
      localization of GGNNV replication complexes, we generated polyclonal antisera
      against protein A, the GGNNV RNA-dependent RNA polymerase. Protein A was detected
      at 5 h postinfection in infected sea bass cells. Biochemical fractionation
      experiments revealed that GGNNV protein A sedimented with intracellular membranes
      upon treatment with an alkaline pH and a high salt concentration, indicating that
      GGNNV protein A is tightly associated with intracellular membranes in infected
      cells. Confocal immunofluorescence microscopy and bromo-UTP incorporation studies
      identified mitochondria as the intracellular site of protein A localization and
      viral RNA synthesis. In addition, protein A fused with green fluorescent protein
      (GFP) was detected in the mitochondria in transfected cells and was demonstrated
      to be tightly associated with intracellular membranes by biochemical
      fractionation analysis and membrane flotation assays, indicating that protein A
      alone was sufficient for mitochondrial localization in the absence of RNA
      replication, nonstructural protein B, or capsid proteins. Three sequence analysis
      programs showed two regions of hydrophobic amino acid residues, amino acids 153
      to 173 and 229 to 249, to be transmembrane domains (TMD) that might contain a
      membrane association domain. Membrane fraction analysis showed that the major
      domain is N-terminal amino acids 215 to 255, containing the predicted TMD from
      amino acids 229 to 249. Using GFP as the reporter by systematically introducing
      deletions of these two regions in the constructs, we further confirmed that the N
      terminal amino acids 215 to 255 of protein A function as a mitochondrial
      targeting signal.

PMID- 15163744
TI  - Cloning and characterization of a bovine adeno-associated virus.
AB  - To better understand the relationship between primate adeno-associated viruses
      (AAVs) and those of other mammals, we have cloned and sequenced the genome of an
      AAV found as a contaminant in two isolates of bovine adenovirus that was reported
      to be serologically distinct from primate AAVs. The bovine AAV (BAAV) genome has
      4,693 bp, and its organization is similar to that of other AAV isolates. The left
      hand open reading frame (ORF) and both inverted terminal repeats (ITRs) have the
      highest homology with the rep ORF and ITRs of AAV serotype 5 (AAV-5) (89 and 96%,
      respectively). However, the right-hand ORF was only 55% identical to the AAV-5
      capsid ORF; it had the highest homology with the capsid ORF of AAV-4 (76%). By
      comparing the BAAV cap sequence with a model of an AAV-4 capsid, we mapped the
      regions of BAAV VP1 that are divergent from AAV-4. These regions are located on
      the outside of the capsid and are partially located in exposed loops. BAAV was
      not neutralized by antisera raised against recombinant AAV-2, AAV-4, or AAV-5,
      and it demonstrated a unique cell tropism profile in four human cancer cell
      lines, suggesting that BAAV might have transduction activity distinct from that
      of other isolates. A murine model of salivary gland gene transfer was used to
      evaluate the in vivo performance of recombinant BAAV. Recombinant BAAV-mediated
      gene transfer was 11 times more efficient than that with AAV-2. Overall, these
      data suggest that vectors based on BAAV could be useful for gene transfer
      applications.

PMID- 15163745
TI  - A bidirectional SF2/ASF- and SRp40-dependent splicing enhancer regulates human
      immunodeficiency virus type 1 rev, env, vpu, and nef gene expression.
AB  - The integrated human immunodeficiency virus type 1 (HIV-1) genome is transcribed
      in a single pre-mRNA that is alternatively spliced into more than 40 mRNAs. We
      characterized a novel bidirectional exonic splicing enhancer (ESE) that regulates
      the expression of the HIV-1 env, vpu, rev, and nef mRNAs. The ESE is localized
      downstream of the vpu-, env-, and nef-specific 3' splice site no. 5. SF2/ASF and
      SRp40 activate the ESE and are required for efficient 3' splice site usage and
      binding of the U1 snRNP to the downstream 5' splice site no. 4. U1 snRNP binding
      to the 5' splice site no. 4 is required for splicing of the rev and nef mRNAs and
      to increase expression of the partially spliced env mRNA. Finally, our results
      indicate that this ESE is necessary for the recruitment of the U1 snRNP to the 5'
      splice site no. 4, even when the 5' splice site and the U1 snRNA have been
      mutated to obtain a perfect complementary match. The ESE characterized here is
      highly conserved in most viral subtypes.

PMID- 15163746
TI  - Ability of the human cytomegalovirus IE1 protein to modulate sumoylation of PML
      correlates with its functional activities in transcriptional regulation and
      infectivity in cultured fibroblast cells.
AB  - In one of the earliest events in human cytomegalovirus (HCMV)-infected cells, the
      major immediate-early (IE) protein IE1 initially targets to and then disrupts the
      nuclear structures known as PML oncogenic domains (PODs) or nuclear domain 10.
      Recent studies have suggested that modification of PML by SUMO is essential to
      form PODs and that IE1 both binds to PML and may disrupt PODs by preventing or
      removing SUMO adducts on PML. In this study, we showed that in contrast to herpes
      simplex virus type 1 (HSV-1) IE110 (ICP0), the loss of sumoylated forms of PML by
      cotransfected IE1 was resistant to the proteasome inhibitor MG132 and that IE1
      did not reduce the level of unmodified PML. Reduced sumoylation of PML was also
      observed in U373 cells after infection with wild-type HCMV and proved to require
      IE1 protein expression. Mutational analysis revealed that the central hydrophobic
      domain of IE1, including Leu174, is required for both PML binding and loss of PML
      sumoylation and confirmed that all IE1 mutants tested that were deficient in
      these functions also failed both to target to PODs and to disrupt PODs. These
      same mutants were also inactive in several reporter gene transactivation assays
      and in inhibition of PML-mediated repression. Importantly, a viral DNA genome
      containing an IE1 gene with a deletion [IE1(Delta290-320)] that was defective in
      these activities was not infectious when transfected into permissive fibroblast
      cells, but the mutant IE1(K450R), which is defective in IE1 sumoylation, remained
      infectious. Our mutational analysis strengthens the idea that interference by IE1
      with both the sumoylation of PML and its repressor activity requires a physical
      interaction with PML that also leads to disruption of PODs. These activities of
      IE1 also correlate with several unusual transcriptional transactivation functions
      of IE1 and may be requirements for efficient initiation of the lytic cycle in
      vivo.

PMID- 15163747
TI  - Lyssavirus matrix protein induces apoptosis by a TRAIL-dependent mechanism
      involving caspase-8 activation.
AB  - Lyssaviruses, which are members of the Rhabdoviridae family, induce apoptosis,
      which plays an important role in the neuropathogenesis of rabies. However, the
      mechanisms by which these viruses mediate neuronal apoptosis have not been
      elucidated. Here we demonstrate that the early induction of apoptosis in a model
      of lyssavirus-infected neuroblastoma cells involves a TRAIL-dependent pathway
      requiring the activation of caspase-8 but not of caspase-9 or caspase-10. The
      activation of caspase-8 results in the activation of caspase-3 and caspase-6, as
      shown by an increase in the cleavage of the specific caspase substrate in
      lyssavirus-infected cells. However, neither caspase-1 nor caspase-2 activity was
      detected during the early phase of infection. Lyssavirus-mediated cell death
      involves an interaction between TRAIL receptors and TRAIL, as demonstrated by
      experiments using neutralizing antibodies and soluble decoy TRAIL-R1/R2
      receptors. We also demonstrated that the decapsidation and replication of
      lyssavirus are essential for inducing apoptosis, as supported by UV inactivation,
      cycloheximide treatment, and the use of bafilomycin A1 to inhibit endosomal
      acidification. Transfection of cells with the matrix protein induced apoptosis
      using pathways similar to those described in the context of viral infection.
      Furthermore, our data suggest that the matrix protein of lyssaviruses plays a
      major role in the early induction of TRAIL-mediated apoptosis by the release of a
      soluble, active form of TRAIL. In our model, Fas ligand (CD95L) appears to play a
      limited role in lyssavirus-mediated neuroblastoma cell death. Similarly, tumor
      necrosis factor alpha does not appear to play an important role.

PMID- 15163748
TI  - Development of a novel helper-dependent adenovirus-Epstein-Barr virus hybrid
      system for the stable transformation of mammalian cells.
AB  - Epstein-Barr virus (EBV) episomes are stably maintained in permissive
      proliferating cell lines due to EBV nuclear antigen 1 (EBNA-1) protein-mediated
      replication and segregation. Previous studies showed the ability of EBV episomes
      to confer long-term transgene expression and correct genetic defects in deficient
      cells. To achieve quantitative delivery of EBV episomes in vitro and in vivo, we
      developed a binary helper-dependent adenovirus (HDA)-EBV hybrid system that
      consists of one HDA vector for the expression of Cre recombinase and a second HDA
      vector that contains all of the sequences for the EBV episome flanked by loxP
      sites. Upon coinfection of cells, Cre expressed from the first vector recombined
      loxP sites on the second vector. The resulting circular EBV episomes expressed a
      transgene and contained the EBV-derived family of repeats, an EBNA-1 expression
      cassette, and 19 kb of human DNA that functions as a replication origin in
      mammalian cells. This HDA-EBV hybrid system transformed 40% of cultured cells.
      Transgene expression in proliferating cells was observed for over 20 weeks under
      conditions that selected for the expression of the transgene. In the absence of
      selection, EBV episomes were lost at a rate of 8 to 10% per cell division.
      Successful delivery of EBV episomes in vivo was demonstrated in the liver of
      transgenic mice expressing Cre from the albumin promoter. This novel gene
      transfer system has the potential to confer long-term episomal transgene
      expression and therefore to correct genetic defects with reduced vector-related
      toxicity and without insertional mutagenesis.

PMID- 15163749
TI  - Contribution of proteoglycans to human immunodeficiency virus type 1 brain
      invasion.
AB  - As a neurotropic virus, human immunodeficiency virus type 1 (HIV-1) invades the
      brain and causes severe neuronal, astrocyte, and myelin damage in AIDS patients.
      To gain access to the brain, HIV-1 must migrate through brain microvascular
      endothelial cells (BMECs), which compose the blood-brain barrier (BBB). Given
      that BMECs lack the entry receptor CD4, HIV-1 must use receptors distinct from
      CD4 to enter these cells. We previously reported that cell surface proteoglycans
      serve as major HIV-1 receptors on primary human endothelial cells. In this study,
      we examined whether proteoglycans also impact cell-free HIV-1 invasion of the
      brain. Using an artificial BBB transmigration assay, we found that both heparan
      and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) are
      abundantly expressed on primary BMECs and promote HIV-1 attachment and entry. In
      contrast, the classical entry receptors, CXCR4 and CCR5, only moderately enhanced
      these processes. HSPGs and CSPGs captured HIV-1 in a gp120-dependent manner.
      However, no correlation between coreceptor usage and transmigration was
      identified. Furthermore, brain-derived viruses did not transmigrate more
      efficiently than lymphoid-derived viruses, suggesting that the ability of HIV-1
      to replicate in the brain does not correlate with its capacity to migrate through
      the BBB as cell-free virus. Given that HIV-1-proteoglycan interactions are based
      on electrostatic contacts between basic residues in gp120 and sulfate groups in
      proteoglycans, HIV-1 may exploit these interactions to rapidly enter and migrate
      through the BBB to invade the brain.

PMID- 15163750
TI  - Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear
      antigen inhibits lytic replication by targeting Rta: a potential mechanism for
      virus-mediated control of latency.
AB  - Like other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV, also
      designated human herpesvirus 8) can establish a latent infection in the infected
      host. During latency a small number of genes are expressed. One of those genes
      encodes latency-associated nuclear antigen (LANA), which is constitutively
      expressed in cells during latent as well as lytic infection. LANA has previously
      been shown to be important for the establishment of latent episome maintenance
      through tethering of the viral genome to the host chromosomes. Under specific
      conditions, KSHV can undergo lytic replication, with the production of viral
      progeny. The immediate-early Rta, encoded by open reading frame 50 of KSHV, has
      been shown to play a critical role in switching from viral latent replication to
      lytic replication. Overexpression of Rta from a heterologous promoter is
      sufficient for driving KSHV lytic replication and the production of viral
      progeny. In the present study, we show that LANA down-modulates Rta's promoter
      activity in transient reporter assays, thus repressing Rta-mediated
      transactivation. This results in a decrease in the production of KSHV progeny
      virions. We also found that LANA interacts physically with Rta both in vivo and
      in vitro. Taken together, our results demonstrate that LANA can inhibit viral
      lytic replication by inhibiting expression as well as antagonizing the function
      of Rta. This suggests that LANA may play a critical role in maintaining latency
      by controlling the switch between viral latency and lytic replication.

PMID- 15163752
TI  - Murine gammaherpesvirus 68 open reading frame 31 is required for viral
      replication.
AB  - Murine gammaherpesvirus 68 (MHV-68) is genetically related to the human
      gammaherpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) and
      Epstein-Barr virus (EBV). It has been proposed as a model for gammaherpesvirus
      infection and pathogenesis. Open reading frame 31 (ORF31) is conserved among the
      Beta- and Gammaherpesvirinae subfamily, and there is no known mammalian homologue
      of this protein. The function of MHV-68 ORF31 and its viral homologues has not
      yet been determined. We described here a primary characterization of this protein
      and its requirement for lytic replication. The native MHV-68 ORF31 was detected
      at peak levels by 24 h postinfection, and the FLAG-tagged and green fluorescent
      protein fusion ORF31 were localized in the cytoplasm and nucleus in a diffuse
      pattern. Two independent experimental approaches were then utilized to
      demonstrate that ORF31 was required for lytic replication. First, small
      interfering RNA generated against ORF31 expression blocked protein expression and
      virus production in transfected cells. Then, two-independent bacterial artificial
      chromosome-derived ORF31-null MHV-68 mutants (31STOP) were generated and found to
      be defective in virus production in fibroblast cells. This defect can be rescued
      in trans by MHV-68 ORF31 and importantly by its KSHV homologue. A repair virus of
      31STOP was also generated by homologous recombination in fibroblast cells.
      Finally, we showed that the defect in ORF31 blocked late lytic protein
      expression. Our results demonstrate that MHV-68 ORF31 is required for viral lytic
      replication, and its function is conserved in its KSHV homologue.

PMID- 15163751
TI  - Adeno-associated virus type 2 VP2 capsid protein is nonessential and can tolerate
      large peptide insertions at its N terminus.
AB  - Direct insertion of amino acid sequences into the adeno-associated virus type 2
      (AAV) capsid open reading frame (cap ORF) is one strategy currently being
      developed for retargeting this prototypical gene therapy vector. While this
      approach has successfully resulted in the formation of AAV particles that have
      expanded or retargeted viral tropism, the inserted sequences have been relatively
      short, linear receptor binding ligands. Since many receptor-ligand interactions
      involve nonlinear, conformation-dependent binding domains, we investigated the
      insertion of full-length peptides into the AAV cap ORF. To minimize disruption of
      critical VP3 structural domains, we confined the insertions to residue 138 within
      the VP1-VP2 overlap, which has been shown to be on the surface of the particle
      following insertion of smaller epitopes. The insertion of coding sequences for
      the 8-kDa chemokine binding domain of rat fractalkine (CX3CL1), the 18-kDa human
      hormone leptin, and the 30-kDa green fluorescent protein (GFP) after residue 138
      failed to lead to formation of particles due to the loss of VP3 expression. To
      test the ability to complement these insertions with the missing capsid proteins
      in trans, we designed a system for producing AAV vectors in which expression of
      one capsid protein is isolated and combined with the remaining two capsid
      proteins expressed separately. Such an approach allows for genetic modification
      of a specific capsid protein across its entire coding sequence leaving the
      remaining capsid proteins unaffected. An examination of particle formation from
      the individual components of the system revealed that genome-containing particles
      formed as long as the VP3 capsid protein was present and demonstrated that the
      VP2 capsid protein is nonessential for viral infectivity. Viable particles
      composed of all three capsid proteins were obtained from the capsid
      complementation groups regardless of which capsid proteins were supplied
      separately in trans. Significant overexpression of VP2 resulted in the formation
      of particles with altered capsid protein stoichiometry. The key finding was that
      by using this system we successfully obtained nearly wild-type levels of
      recombinant AAV-like particles with large ligands inserted after residue 138 in
      VP1 and VP2 or in VP2 exclusively. While insertions at residue 138 in VP1
      significantly decreased infectivity, insertions at residue 138 that were
      exclusively in VP2 had a minimal effect on viral assembly or infectivity.
      Finally, insertion of GFP into VP1 and VP2 resulted in a particle whose
      trafficking could be temporally monitored by using confocal microscopy. Thus, we
      have demonstrated a method that can be used to insert large (up to 30-kDa)
      peptide ligands into the AAV particle. This system allows greater flexibility
      than current approaches in genetically manipulating the composition of the AAV
      particle and, in particular, may allow vector retargeting to alternative
      receptors requiring interaction with full-length conformation-dependent peptide
      ligands.

PMID- 15163753
TI  - Short duration of elevated vIRF-1 expression during lytic replication of human
      herpesvirus 8 limits its ability to block antiviral responses induced by alpha
      interferon in BCBL-1 cells.
AB  - Human herpesvirus 8 (HHV-8) encodes multiple proteins that disrupt the host
      antiviral response, including viral interferon (IFN) regulatory factor 1 (vIRF
      1). The product of the vIRF-1 gene blocks responses to IFN when overexpressed by
      transfection, but the functional consequence of vIRF-1 that is expressed during
      infection with HHV-8 is not known. These studies demonstrate that BCBL-1 cells
      that were latently infected with HHV-8 expressed low levels of vIRF-1 that were
      associated with PML bodies, whereas much higher levels of vIRF-1 were transiently
      expressed during the lytic phase of HHV-8 replication. The low levels of vIRF-1
      that were associated with PML bodies were insufficient to block alpha IFN (IFN
      alpha)-induced alterations in gene expression, whereas cells that expressed high
      levels of vIRF-1 were resistant to some changes induced by IFN-alpha, including
      the expression of the double-stranded-RNA-activated protein kinase. High levels
      of vIRF-1 were expressed for only a short period during the lytic cascade, so
      many cells with HHV-8 in the lytic phase responded to IFN-alpha with increased
      expression of antiviral genes and enhanced apoptosis. Furthermore, the production
      of infectious virus was severely compromised when IFN-alpha was present early
      during the lytic cascade. These studies indicate that the transient expression of
      high levels of vIRF-1 is inadequate to subvert many of the antiviral effects of
      IFN-alpha so that IFN-alpha can effectively induce apoptosis and block production
      of infectious virus when present early in the lytic cascade of HHV-8.

PMID- 15163754
TI  - Late assembly motifs of human T-cell leukemia virus type 1 and their relative
      roles in particle release.
AB  - Three late assembly domain consensus motifs, namely PTAP, PPPY, and LYPXL, have
      been identified in different retroviruses. They have been shown to interact with
      the cellular proteins TSG101, Nedd4, and AP2 or AIP, respectively. Human T-cell
      leukemia virus type 1 (HTLV-1) has a PPPY and a PTAP motif, separated by two
      amino acids, located at the end of MA, but only the PPPY motif is conserved in
      the deltaretrovirus group. Like other retroviral peptides carrying the late
      motif, MA is mono- or di-ubiquitinated. A mutational analysis showed that 90% of
      PPPY mutant particles were retained in the cell compared to 15% for the wild-type
      virus. Mutations of the PTAP motif resulted in a 20% decrease in particle
      release. In single-cycle infectivity assays, the infectious titers of late motif
      mutants correlated with the amounts of released virus, as determined by an enzyme
      linked immunosorbent assay. We observed binding of MA to the WW domains of the
      Nedd4 family member WWP1 but not to the amino-terminal ubiquitin E2 variant
      domain of TSG101 in mammalian two-hybrid analyses. The binding to WWP1 was
      eliminated when the PPPY motif was mutated. However, MA showed binding to TSG101
      in the yeast two-hybrid system that was dependent on an intact PTAP motif. A
      dominant-negative (DN) mutant of WWP1 could inhibit budding of the intact HTLV-1
      virus. In contrast, DN TSG101 only affected the release of virus-like particles
      encoded by Gag expression plasmids. Electron and fluorescent microscopy showed
      that Gag accumulates in large patches in the membranes of cells expressing
      viruses with PPPY mutations. Very few tethered immature particles could be
      detected in these samples, suggesting that budding is impaired at an earlier step
      than in other retroviruses.

PMID- 15163755
TI  - Role of an arbovirus nonstructural protein in cellular pathogenesis and virus
      release.
AB  - The insect-borne Bluetongue virus (BTV) is considered the prototypic Orbivirus, a
      member of the Reovirus family. One of the hallmarks of Orbivirus infection is the
      production of large numbers of intracellular tubular structures of unknown
      function. For BTV these structures are formed as the polymerization product of a
      single 64-kDa nonstructural protein, NS1, encoded by the viral double-stranded
      RNA genome segment 6. Although the NS1 protein is the most abundant viral protein
      synthesized in infected cells, its function has yet to be determined. One
      possibility is that NS1 tubules may be involved in the translocation of newly
      formed viral particles to the plasma membrane, and NS1-specific monoclonal
      antibodies have been shown to react with viral particles leaving infected cells.
      In the present study we generated a mammalian cell line that expresses a
      recombinant single-chain antibody fragment (scFv) derived from an NS1-specific
      monoclonal antibody (10B1) and analyzed the effect that this intracellular
      antibody has on BTV replication. Normally, BTV infection of mammalian cells in
      culture results in a severe cytopathic effect within 24 to 48 h postinfection
      manifested by cell rounding, apoptosis, and lytic release of virions into the
      culture medium. However, infection of scFv-expressing cells results in a marked
      reduction in the stability of NS1 and formation of NS1 tubules, a decrease in
      cytopathic effect, an increased release of infectious virus into the culture
      medium, and budding of virions from the plasma membrane. These results suggest
      that NS1 tubules play a direct role in the cellular pathogenesis and
      morphogenesis of BTV.

PMID- 15163757
TI  - Molecular population genetics of Cucumber mosaic virus in California: evidence
      for founder effects and reassortment.
AB  - The structure and genetic diversity of a California Cucumber mosaic virus (CMV)
      population was assessed by single-strand conformation polymorphism and nucleotide
      sequence analyses of genomic regions 2b, CP, MP, and the 3' nontranslated region
      of RNA3. The California CMV population exhibited low genetic diversity and was
      composed of one to three predominant haplotypes and a large number of minor
      haplotypes for specific genomic regions. Extremely low diversity and close
      evolutionary relationships among isolates in a subpopulation suggested that
      founder effects might play a role in shaping the genetic structure. Phylogenetic
      analysis indicated a naturally occurring reassortant between subgroup IA and IB
      isolates and potential reassortants between subgroup IA isolates, suggesting that
      genetic exchange by reassortment contributed to the evolution of the California
      CMV population. Analysis of various population genetics parameters and
      distribution of synonymous and nonsynonymous mutations revealed that different
      coding regions and even different parts of coding regions were under different
      evolutionary constraints, including a short region of the 2b gene for which
      evidence suggests possible positive selection.

PMID- 15163756
TI  - Herpesvirus protease inhibition by dimer disruption.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), like all herpesviruses, encodes a
      protease (KSHV Pr), which is necessary for the viral lytic cycle. Herpesvirus
      proteases function as obligate dimers; however, each monomer has an intact,
      complete active site which does not interact directly with the other monomer
      across the dimer interface. Protein grafting of an interfacial KSHV Pr alpha
      helix onto a small stable protein, avian pancreatic polypeptide, generated a
      helical 30-amino-acid peptide designed to disrupt the dimerization of KSHV Pr.
      The chimeric peptide was optimized through protein modeling of the KSHV Pr
      peptide complex. Circular dichroism analysis and gel filtration chromatography
      revealed that the rationally designed peptide adopts a helical conformation and
      is capable of disrupting KSHV Pr dimerization, respectively. Additionally, the
      optimized peptide inhibits KSHV Pr activity by 50% at a approximately 200-fold
      molar excess of peptide to KSHV Pr, and the dissociation constant was estimated
      to be 300 microM. Mutagenesis of the interfacial residue M197 to a leucine
      resulted in an inhibitory concentration which was twofold higher for KSHV Pr
      M197L than for KSHV Pr, in agreement with the model that the dimer interface is
      involved in peptide binding. These results indicate that the dimer interface, as
      well as the active sites, of herpesvirus proteases is a viable target for
      inhibiting enzyme activity.

PMID- 15163758
TI  - Rinderpest virus phosphoprotein gene is a major determinant of species-specific
      pathogenicity.
AB  - We previously demonstrated that the rinderpest virus (RPV) hemagglutinin (H)
      protein plays an important role in determining host range but that other viral
      proteins are clearly required for full RPV pathogenicity to be manifest in
      different species. To examine the effects of the RPV nucleocapsid (N) protein and
      phosphoprotein (P) genes on RPV cross-species pathogenicity, we constructed two
      new recombinant viruses in which the H and P or the H, N, and P genes of the
      cattle-derived RPV RBOK vaccine were replaced with those from the rabbit-adapted
      RPV-Lv strain, which is highly pathogenic in rabbits. The viruses rescued were
      designated recombinant RPV-lapPH (rRPV-lapPH) and rRPV-lapNPH, respectively.
      Rabbits inoculated with RPV-Lv become feverish and show leukopenia and a decrease
      in body weight gain, while clinical signs of infection are never observed in
      rabbits inoculated with RPV-RBOK or with rRPV-lapH. However, rabbits inoculated
      with either rRPV-lapPH or rRPV-lapNPH became pyrexic and showed leukopenia.
      Further, histopathological lesions and high virus titers were clearly observed in
      the lymphoid tissues from animals infected with rRPV-lapPH or rRPV-lapNPH,
      although they were not observed in rabbits infected with RPV-RBOK or rRPV-lapH.
      The clinical, virological, and histopathological signs in rabbits infected with
      the two new recombinant viruses did not differ significantly; therefore, the RPV
      P gene was considered to be a key determinant of cross-species pathogenicity.

PMID- 15163760
TI  - Postattachment events associated with viral entry are necessary for induction of
      interferon-stimulated genes by human cytomegalovirus.
AB  - Utilizing a human cytomegalovirus-specific fusion inhibitor and an
      antiglycoprotein H antibody, we studied the role of virion fusion in interferon
      stimulated gene (ISG) induction. Our results indicate that ISG induction does not
      occur when virion-mediated, post-high-affinity attachment events are inhibited by
      either reagent. Thus, virion-mediated postattachment events, such as fusion, are
      required for ISG induction.

PMID- 15163759
TI  - Target specificity of human immunodeficiency virus type 1 NCp7 requires an intact
      conformation of its CCHC N-terminal zinc finger.
AB  - The modification of zinc-binding residues inside the conserved CCHC motif of
      human immunodeficiency virus type 1 NCp7, in particular into CCHH, induces a
      complete loss of infectivity. Since the mutant His28NCp7 has been shown to be
      devoid of infectivity in vivo, the structure-function relationships of the mutant
      His28(12-53)NCp7 were investigated by nuclear magnetic resonance and surface
      plasmonic resonance. Although the Cys28-->His mutation modifies drastically the
      structure of the core domain (residues 12 to 53) of NCp7, His28(12-53)NCp7 still
      interacts with a 10-fold-lower affinity to specific nucleic acid targets, such as
      SL3, a stem-loop critically involved in viral RNA packaging, and without affinity
      change with the nonspecific, single-stranded nucleic acid poly(T). Moreover,
      His28(12-53)NCp7 and native (12-53)NCp7 displayed the same affinity with reverse
      transcriptase, but the natures of the complexes are probably different,
      accounting for the drastic reduction in the amount of RNA packaged in the mutated
      virus. We propose a structural model of His28(12-53)NCp7 that provides insights
      into the NCp7 structural features necessary for target recognition and that shows
      that the specific native structure of the zinc finger domain is strictly required
      for the optimal target selectivity of NCp7.

PMID- 15163761
TI  - Engagement of ICAM-3 provides a costimulatory signal for human immunodeficiency
      virus type 1 replication in both activated and quiescent CD4+ T lymphocytes:
      implications for virus pathogenesis.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication is regulated by several
      extracellular signals. We demonstrate that intercellular adhesion molecule 3
      (ICAM-3) acts as a costimulating molecule to increase HIV-1 transcription and
      viral production, a process allowing productive infection of quiescent CD4+ T
      lymphocytes. The present work suggests an important role for ICAM-3 in HIV-1
      replication.

PMID- 15163762
TI  - Nodamura virus nonstructural protein B2 can enhance viral RNA accumulation in
      both mammalian and insect cells.
AB  - During infection of both vertebrate and invertebrate cell lines, the
      alphanodavirus Nodamura virus (NoV) expresses two nonstructural proteins of
      different lengths from the B2 open reading frame. The functions of these proteins
      have yet to be determined, but B2 of the related Flock House virus suppresses RNA
      interference both in Drosophila cells and in transgenic plants. To examine
      whether the NoV B2 proteins had similar functions, we compared the replication of
      wild-type NoV RNA with that of mutants unable to make the B2 proteins. We
      observed a defect in the accumulation of mutant viral RNA that varied in extent
      from negligible in some cell lines (e.g., baby hamster kidney cells) to severe in
      others (e.g., human HeLa and Drosophila DL-1 cells). These results are consistent
      with the notion that the NoV B2 proteins act to circumvent an innate antiviral
      response such as RNA interference that differs in efficacy among different host
      cells.

PMID- 15163763
TI  - RNA stem-loop enhanced expression of previously non-expressible genes.
AB  - The key step in bacterial translation is formation of the pre-initiation complex.
      This requires initial contacts between mRNA, fMet-tRNA and the 30S subunit of the
      ribosome, steps that limit the initiation of translation. Here we report a method
      for improving translational initiation, which allows expression of several
      previously non-expressible genes. This method has potential applications in
      heterologous protein synthesis and high-throughput expression systems. We
      introduced a synthetic RNA stem-loop (stem length, 7 bp; DeltaG(0) = -9.9
      kcal/mol) in front of various gene sequences. In each case, the stem-loop was
      inserted 15 nt downstream from the start codon. Insertion of the stem-loop
      allowed in vitro expression of five previously non-expressible genes and enhanced
      the expression of all other genes investigated. Analysis of the RNA structure
      proved that the stem-loop was formed in vitro, and demonstrated that
      stabilization of the ribosome binding site is due to stem-loop introduction. By
      theoretical RNA structure analysis we showed that the inserted RNA stem-loop
      suppresses long-range interactions between the translation initiation domain and
      gene-specific mRNA sequences. Thus the inserted RNA stem-loop supports the
      formation of a separate translational initiation domain, which is more accessible
      to ribosome binding.

PMID- 15163768
TI  - IQPNNI: moving fast through tree space and stopping in time.
AB  - An efficient tree reconstruction method (IQPNNI) is introduced to reconstruct a
      phylogenetic tree based on DNA or amino acid sequence data. Our approach combines
      various fast algorithms to generate a list of potential candidate trees. The key
      ingredient is the definition of so-called important quartets (IQs), which allow
      the computation of an intermediate tree in O(n(2)) time for n sequences. The
      resulting tree is then further optimized by applying the nearest neighbor
      interchange (NNI) operation. Subsequently a random fraction of the sequences is
      deleted from the best tree found so far. The deleted sequences are then re
      inserted in the smaller tree using the important quartet puzzling (IQP)
      algorithm. These steps are repeated several times and the best tree, with respect
      to the likelihood criterion, is considered as the inferred phylogenetic tree.
      Moreover, we suggest a rule which indicates when to stop the search. Simulations
      show that IQPNNI gives a slightly better accuracy than other programs tested.
      Moreover, we applied the approach to 218 small subunit rRNA sequences and 500
      rbcL sequences. We found trees with higher likelihood compared to the results by
      others. A program to reconstruct DNA or amino acid based phylogenetic trees is
      available online (http://www.bi.uni-duesseldorf.de/software/iqpnni).

PMID- 15163766
TI  - Genomic analysis of Drosophila melanogaster telomeres: full-length copies of HeT
      A and TART elements at telomeres.
AB  - The repetitive nature of heterochromatin hampers its analysis in general genome
      sequencing projects. Specific studies are needed to extend the sequence into
      telomeric and centromeric heterochromatin. Drosophila telomeres lack the
      telomerase-generated repeats that are characteristic of other eukaryotic
      chromosomes. Instead, they consist of tandem arrays of HeT-A and TART elements.
      Herein, we present the genomic organization of the telomeres in the isogenic
      strain (y; cn bw sp) that was used for the Drosophila melanogaster sequencing
      project. The data indicate that the canonical features of telomere organization
      are widely conserved in evolution. In addition, we have identified full-length
      elements, likely competent elements, for HeT-A and TART.

PMID- 15163767
TI  - Evolutionary process of amino acid biosynthesis in Corynebacterium at the whole
      genome level.
AB  - Corynebacterium glutamicum, which is the closest relative of Corynebacterium
      efficiens, is widely used for the large scale production of many kinds of amino
      acids, particularly glutamic acid and lysine, by fermentation. Corynebacterium
      diphtheriae, which is well known as a human pathogen, is also closely related to
      these two species of Corynebacteria, but it lacks such productivity of amino
      acids. It is an important and interesting question to ask how those closely
      related bacterial species have undergone such significant functional
      differentiation in amino acid biosynthesis. The main purpose of the present study
      is to clarify the evolutionary process of functional differentiation among the
      three species of Corynebacteria by conducting a comparative analysis of genome
      sequences. When Mycobacterium and Streptomyces were used as out groups, our
      comparative study suggested that the common ancestor of Corynebacteria already
      possessed almost all of the gene sets necessary for amino acid production.
      However, C. diphtheriae was found to have lost the genes responsible for amino
      acid production. Moreover, we found that the common ancestor of C. efficiens and
      C. glutamicum have acquired some of genes responsible for amino acid production
      by horizontal gene transfer. Thus, we conclude that the evolutionary events of
      gene loss and horizontal gene transfer must have been responsible for functional
      differentiation in amino acid biosynthesis of the three species of
      Corynebacteria.

PMID- 15163769
TI  - The cation/Ca(2+) exchanger superfamily: phylogenetic analysis and structural
      implications.
AB  - Cation/Ca(2+) exchangers are an essential component of Ca(2+) signaling pathways
      and function to transport cytosolic Ca(2+) across membranes against its
      electrochemical gradient by utilizing the downhill gradients of other cation
      species such as H(+), Na(+), or K(+). The cation/Ca(2+) exchanger superfamily is
      composed of H(+)/Ca(2+) exchangers and Na(+)/Ca(2+) exchangers, which have been
      investigated extensively in both plant cells and animal cells. Recently,
      information from completely sequenced genomes of bacteria, archaea, and
      eukaryotes has revealed the presence of genes that encode homologues of
      cation/Ca(2+) exchangers in many organisms in which the role of these exchangers
      has not been clearly demonstrated. In this study, we report a comprehensive
      sequence alignment and the first phylogenetic analysis of the cation/Ca(2+)
      exchanger superfamily of 147 sequences. The results present a framework for
      structure-function relationships of cation/Ca(2+) exchangers, suggesting unique
      signature motifs of conserved residues that may underlie divergent functional
      properties. Construction of a phylogenetic tree with inclusion of cation/Ca(2+)
      exchangers with known functional properties defines five protein families and the
      evolutionary relationships between the members. Based on this analysis, the
      cation/Ca(2+) exchanger superfamily is classified into the YRBG, CAX, NCX, and
      NCKX families and a newly recognized family, designated CCX. These findings will
      provide guides for future studies concerning structures, functions, and
      evolutionary origins of the cation/Ca(2+) exchangers.

PMID- 15163770
TI  - Smoking ban--made in Ireland, for home use and for export.

PMID- 15163771
TI  - Torment.

PMID- 15163772
TI  - Chronic thromboembolic pulmonary hypertension--not so rare after all.

PMID- 15163773
TI  - Prevalence of prostate cancer among men with a prostate-specific antigen level <
      or =4.0 ng per milliliter.
AB  - BACKGROUND: The optimal upper limit of the normal range for prostate-specific
      antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among
      men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per
      milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459
      were randomly assigned to receive placebo and had an annual measurement of PSA
      and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA
      level of more than 4.0 ng per milliliter or an abnormal digital rectal
      examination, had a final PSA determination, and underwent a prostate biopsy after
      being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to
      91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449
      cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of
      prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per
      milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter,
      17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9
      percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent
      among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high
      grade cancers increased from 12.5 percent of cancers associated with a PSA level
      of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA
      level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate
      cancer, including high-grade cancers, is not rare among men with PSA levels of
      4.0 ng per milliliter or less--levels generally thought to be in the normal
      range.

PMID- 15163774
TI  - A comparison of albumin and saline for fluid resuscitation in the intensive care
      unit.
AB  - BACKGROUND: It remains uncertain whether the choice of resuscitation fluid for
      patients in intensive care units (ICUs) affects survival. We conducted a
      multicenter, randomized, double-blind trial to compare the effect of fluid
      resuscitation with albumin or saline on mortality in a heterogeneous population
      of patients in the ICU. METHODS: We randomly assigned patients who had been
      admitted to the ICU to receive either 4 percent albumin or normal saline for
      intravascular-fluid resuscitation during the next 28 days. The primary outcome
      measure was death from any cause during the 28-day period after randomization.
      RESULTS: Of the 6997 patients who underwent randomization, 3497 were assigned to
      receive albumin and 3500 to receive saline; the two groups had similar baseline
      characteristics. There were 726 deaths in the albumin group, as compared with 729
      deaths in the saline group (relative risk of death, 0.99; 95 percent confidence
      interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ
      and multiple-organ failure was similar in the two groups (P=0.85). There were no
      significant differences between the groups in the mean (+/-SD) numbers of days
      spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline
      group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6,
      respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7,
      respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/
      2.0, respectively; P=0.41). CONCLUSIONS: In patients in the ICU, use of either 4
      percent albumin or normal saline for fluid resuscitation results in similar
      outcomes at 28 days.

PMID- 15163775
TI  - Incidence of chronic thromboembolic pulmonary hypertension after pulmonary
      embolism.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTPH) is associated
      with considerable morbidity and mortality. Its incidence after pulmonary embolism
      and associated risk factors are not well documented. METHODS: We conducted a
      prospective, long-term, follow-up study to assess the incidence of symptomatic
      CTPH in consecutive patients with an acute episode of pulmonary embolism but
      without prior venous thromboembolism. Patients with unexplained persistent
      dyspnea during follow-up underwent transthoracic echocardiography and, if
      supportive findings were present, ventilation-perfusion lung scanning and
      pulmonary angiography. CTPH was considered to be present if systolic and mean
      pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg, respectively;
      pulmonary-capillary wedge pressure was normal; and there was angiographic
      evidence of disease. RESULTS: The cumulative incidence of symptomatic CTPH was
      1.0 percent (95 percent confidence interval, 0.0 to 2.4) at six months, 3.1
      percent (95 percent confidence interval, 0.7 to 5.5) at one year, and 3.8 percent
      (95 percent confidence interval, 1.1 to 6.5) at two years. No cases occurred
      after two years among the patients with more than two years of follow-up data.
      The following increased the risk of CTPH: a previous pulmonary embolism (odds
      ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion
      defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic
      pulmonary embolism at presentation (odds ratio, 5.70). CONCLUSIONS: CTPH is a
      relatively common, serious complication of pulmonary embolism. Diagnostic and
      therapeutic strategies for the early identification and prevention of CTPH are
      needed.

PMID- 15163776
TI  - Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in
      blacks and non-Hispanic whites.
AB  - BACKGROUND: Several small studies have reported a lower response rate to
      interferon alfa among black patients with chronic hepatitis C infection than
      among white patients. The increased prevalence of infection with hepatitis C
      virus (HCV) genotype 1, which has a lower response rate than other genotypes, has
      been suggested as the cause. METHODS: We treated 100 black patients and 100 non
      Hispanic white patients with chronic hepatitis C with peginterferon alfa-2b and
      ribavirin for 48 weeks. Enrollment was controlled so that the two groups had
      similar proportions of patients with genotype 1 infection. The primary end point
      was a sustained virologic response, which was defined as a negative test for
      serum HCV RNA six months after the completion of therapy. RESULTS: In both
      cohorts, 98 percent of patients had genotype 1 infection. The rate of sustained
      virologic response was higher among non-Hispanic white patients than among black
      patients (52 percent vs.19 percent, P<0.001). The black patients also had
      significantly lower rates of virologic response at 12 weeks and at the end of
      treatment. Multivariable analyses examining sociodemographic and clinical
      characteristics found that black race was the only variable significantly
      associated with the difference in response rate. CONCLUSIONS: Black patients with
      chronic hepatitis C have a lower rate of response to treatment with peginterferon
      alfa-2b and ribavirin than non-Hispanic white patients, a difference that is not
      explained by differences in the viral genotype.

PMID- 15163777
TI  - Diverse causes of hypoglycemia-associated autonomic failure in diabetes.

PMID- 15163778
TI  - Images in clinical medicine. Unusual cystitis.

PMID- 15163779
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 17-2004. A 42-year-old woman with cardiac arrest several weeks
      after an ankle fracture.

PMID- 15163780
TI  - Prostate cancers in men with low PSA levels--must we find them?

PMID- 15163781
TI  - Is albumin safe?

PMID- 15163782
TI  - Forcible medication for courtroom competence--the case of Charles Sell.

PMID- 15163783
TI  - Targeting gene therapy for osteogenesis imperfecta.

PMID- 15163784
TI  - Excision margins in high-risk malignant melanoma.

PMID- 15163785
TI  - Alendronate versus calcitriol for prevention of bone loss after cardiac
      transplantation.

PMID- 15163786
TI  - Predicting outcomes in chronic obstructive pulmonary disease.

PMID- 15163787
TI  - Effusive-constrictive pericarditis.

PMID- 15163788
TI  - Medical mystery: painless ulcers--the answer.

PMID- 15163789
TI  - Case 6-2004: severe burns from a nightclub fire.

PMID- 15163790
TI  - An acute hypertensive episode triggered by an ambulatory blood-pressure
      monitoring device.

PMID- 15163791
TI  - Images in clinical medicine. Sarcoptes scabiei infestation.

PMID- 15163792
TI  - A concise, total synthesis of the TMC-95A/B proteasome inhibitors.
AB  - A concise, total synthesis of the proteasome inhibitors TMC-95A/B has been
      accomplished. The synthesis features the use of an L-serine-derived E-selective
      modified Julia olefination reaction to ultimately control the stereochemical
      outcome of the highly oxidized tryptophan fragment. Additionally, the limited use
      of protecting groups at a late stage of the total synthesis allowed for its
      completion in an efficient manner.

PMID- 15163794
TI  - Selective deposition of a gadolinium(III) cluster in a hole opening of single
      wall carbon nanohorn.
AB  - Selective synthesis of particles of angstrom to nanometer size consisting of one
      to many metal atoms is instrumental in various applications, but it has been
      hampered by the tendency of the metal atom to form large clusters. We found, as
      studied by the state-of-the-art electron microscopic technique, a strategy to
      produce metal-containing nanoparticles isolated from each other by depositing
      metal atoms in a hydrophilic hole on or in the interior of a carbon nanotube as
      demonstrated by the reaction of Gd(OAc)(3) with oxidized single-wall nanohorns.
      Besides the potential utilities of the deposited metal clusters, the metal
      deposition protocol provides a method to control permeation of molecules through
      such openings.

PMID- 15163793
TI  - The cholesterol membrane anchor of the Hedgehog protein confers stable membrane
      association to lipid-modified proteins.
AB  - The Hedgehog proteins are potent organizers of animal development. They carry a
      cholesterol ester at the C terminus of their signaling domain. The membrane
      anchoring mediated by this lipophilic modification was studied by means of an
      approach integrating cell biology, biochemistry, biophysics, and organic
      chemistry techniques. Sterol-modified and fluorescent-labeled Hedgehog-derived
      peptides and proteins were synthesized and investigated in biophysical and cell
      biological assays. These experiments revealed that cholesterol alone anchors
      proteins to membranes with significant strength and half-times for spontaneous
      desorption of several hours. Its membrane anchoring ability is comparable to dual
      lipidation motifs such as double geranylgeranylation or S-palmitoylation plus S
      farnesylation found in other lipidated proteins. The experiments also demonstrate
      that membrane binding changes dramatically if short lipidated peptides are
      equipped with a large protein. These data suggest that for Hedgehog release and
      subsequent signaling an interaction partner such as the Dispatched protein is
      necessary. In addition to these findings the described approach allows one to
      correlate biophysical data obtained with model peptides with data determined with
      fully functional proteins and to combine results from in vitro and in vivo
      experiments. It should be generally applicable to other membrane anchors and
      proteins.

PMID- 15163795
TI  - A unified approach to the tedanolides: total synthesis of (+)-13-deoxytedanolide.
AB  - A unified approach for the construction of the potent marine antitumor agents (+)
      tedanolide (1) and (+)-13-deoxytedanolide (2) is described. Highlights of the
      synthetic strategy include the development of a versatile bifunctional dithiane
      vinyl iodide linchpin, the unorthodox use of the Evans-Tishchenko reaction, and a
      late-stage high-risk stereocontrolled introduction of the C(18,19) epoxide to
      achieve a total synthesis of (+)-13-deoxytedanolide (2).

PMID- 15163796
TI  - Variation in xylem structure from tropics to tundra: evidence from vestured pits.
AB  - Bordered pits play an important role in permitting water flow among adjacent
      tracheary elements in flowering plants. Variation in the bordered pit structure
      is suggested to be adaptive in optimally balancing the conflict between hydraulic
      efficiency (conductivity) and safety from air entry at the pit membrane (air
      seeding). The possible function of vestured pits, which are bordered pits with
      protuberances from the secondary cell wall of the pit chamber, could be increased
      hydraulic resistance or minimized vulnerability to air seeding. These functional
      hypotheses have to be harmonized with the notion that the vestured or nonvestured
      nature of pits contains strong phylogenetic signals (i.e., often characterize
      large species-rich clades with broad ecological ranges). A literature survey of
      11,843 species covering 6,428 genera from diverse climates indicates that the
      incidence of vestured pits considerably decreases from tropics to tundra. The
      highest frequencies of vestured pits occur in deserts and tropical seasonal
      woodlands. Moreover, a distinctly developed network of branched vestures is
      mainly restricted to warm habitats in both mesic and dry (sub)tropical lowlands,
      whereas vestures in woody plants from cold and boreal arctic environments are
      usually minute and simple. A similar survey of the frequency of exclusively
      scalariform perforation plates illustrates that the major ecological trend of
      this feature is opposite that of vestured pits. These findings provide previously
      undescribed insights suggesting that vessels with vestured pits and simple
      perforation plates function as an efficient hydraulic system in plants growing in
      warm environments with periodical or continuous drought stress.

PMID- 15163797
TI  - Distinct migrating and nonmigrating dendritic cell populations are involved in
      MHC class I-restricted antigen presentation after lung infection with virus.
AB  - During lung infection with virus, airway-derived dendritic cells (DC) have been
      thought to be the dominant cell type involved in acquisition, transport, and
      direct antigen presentation for cytotoxic T lymphocyte priming. Contrary to this
      view, we have found that both an airway-derived CD8alpha(-)CD11b(-) DC subset and
      distinct CD8alpha(+) lymph node resident DC can present class I-restricted
      antigens after lung infection with influenza virus or herpes simplex virus 1.
      Presentation by a nonairway-derived DC population argues that cytotoxic T
      lymphocyte priming may involve interplay between different DC subsets, not all of
      which originate within the site of infection.

PMID- 15163798
TI  - Artificially ambiguous genetic code confers growth yield advantage.
AB  - A primitive genetic code is thought to have encoded statistical, ambiguous
      proteins in which more than one amino acid was inserted at a given codon. The
      relative vitality of organisms bearing ambiguous proteins and the kinds of
      pressures that forced development of the highly specific modern genetic code are
      unknown. Previous work demonstrated that, in the absence of selective pressure,
      enforced ambiguity in cells leads to death or to sequence reversion to eliminate
      the ambiguous phenotype. Here, we report the creation of a nonreverting strain of
      bacteria that produced statistical proteins. Ablating the editing activity of
      isoleucyl-tRNA synthetase resulted in an ambiguous code in which, through
      supplementation of a limited supply of isoleucine with an alternative amino acid
      that was noncoding, the mutant generating statistical proteins was favored over
      the wild-type isogenic strain. Such organisms harboring statistical proteins
      could have had an enhanced adaptive capacity and could have played an important
      role in the early development of living systems.

PMID- 15163799
TI  - Seven in absentia homolog 1A mediates ubiquitination and degradation of group 1
      metabotropic glutamate receptors.
AB  - Seven in absentia homolog 1A (Siah1A) is a member of the RING-finger-containing
      E3 ubiquitin ligases and has been shown to bind to the Siah-interacting domain
      (SID) at the carboxyl-terminal tails of the long splice forms of group 1
      metabotropic glutamate receptors (mGluR1a and mGluR5). We examined the function
      of Siah1A in ubiquitination and degradation of group 1 mGluRs in heterologously
      expressing cell lines. Coexpression of Siah1A markedly decreased the SID
      containing splice forms of group 1 mGluRs but not the SID-lacking mGluR1b splice
      form or the SID-deleted mGluR1a mutant. The decrease of mGluR1a resulted from
      accelerated protein turnover, as revealed by pulse-chase experiments. The Siah1A
      mediated degradation of group 1 mGluRs was abrogated by not only mutations at the
      RING-finger domain of Siah1A but also treatment with a proteasome inhibitor.
      Siah1A coexpression induced strong ubiquitination of group 1 mGluRs. Replacements
      of lysine residues with arginine showed that Siah1A-mediated ubiquitination
      occurs at multiple lysine residues spanning both the seven-transmembrane region
      and carboxyl-terminal tail of mGluR5. In situ hybridization histochemistry showed
      a wide-spread distribution of Siah1 mRNAs, with high expression in the
      hippocampal pyramidal neurons and cerebellar Purkinje cells. Group 1 mGluRs play
      critical roles in the neural plasticity in both the hippocampal neurons and
      Purkinje cells. This investigation indicates that Siah1A serves as a selective
      ubiquitin ligase that mediates ubiquitination-dependent degradation of long
      splice variants of group 1 mGluRs and would contribute to posttranslational down
      regulation of group 1 mGluRs.

PMID- 15163801
TI  - Can microbubbles be targeted to lymph nodes?

PMID- 15163800
TI  - Can optical molecular imaging techniques with catheter-based approaches be used
      for disease detection?

PMID- 15163802
TI  - Personalized medicine.

PMID- 15163803
TI  - Cancer upgrades at excisional biopsy after diagnosis of atypical lobular
      hyperplasia or lobular carcinoma in situ at core-needle biopsy: some reasons why.

PMID- 15163804
TI  - Primer for clinician scholars in academic radiology.

PMID- 15163805
TI  - MR imaging: its development and the recent Nobel Prize.

PMID- 15163806
TI  - Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR
      imaging findings in normal-appearing white matter.
AB  - PURPOSE: To prospectively determine hemodynamic changes in the normal-appearing
      white matter (NAWM) of patients with relapsing-remitting multiple sclerosis (RR
      MS) by using dynamic susceptibility contrast material-enhanced perfusion magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: Conventional MR imaging (which
      included acquisition of pre- and postcontrast transverse T1-weighted, fluid
      attenuated inversion recovery, and T2-weighted images) and dynamic susceptibility
      contrast-enhanced T2*-weighted MR imaging were performed in 17 patients with RR
      MS (five men and 12 women; median age, 38.4 years; age range, 27.6-56.9 years)
      and 17 control patients (seven men and 10 women; median age, 42.0 years; age
      range, 18.7-62.5 years). Absolute cerebral blood volume (CBV), absolute cerebral
      blood flow (CBF), and mean transit time (MTT) (referenced to an arterial input
      function by using an automated method) were determined in periventricular,
      intermediate, and subcortical regions of NAWM at the level of the lateral
      ventricles. Least-squares regression analysis (controlled for age and sex) was
      used to compare perfusion measures in each region between patients with RR-MS and
      control patients. Repeated-measures analysis of variance and the Tukey honestly
      significant difference test were used to perform pairwise comparison of brain
      regions in terms of each perfusion measure. RESULTS: Each region of NAWM in
      patients with RR-MS had significantly decreased CBF (P <.005) and prolonged MTT
      (P <.001) compared with the corresponding region in control patients. No
      significant differences in CBV were found between patients with RR-MS and control
      patients in any of the corresponding areas of NAWM examined. In control patients,
      periventricular NAWM regions had significantly higher CBF (P =.03) and CBV (P
      =.04) than did intermediate NAWM regions. No significant regional differences in
      CBF, CBV, or MTT were found in patients with RR-MS. CONCLUSION: The NAWM of
      patients with RR-MS shows decreased perfusion compared with that of controls.

PMID- 15163808
TI  - Early MR lymphography with gadofluorine M in rabbits.
AB  - PURPOSE: To investigate the dose and time dependency of gadofluorine M for lymph
      node imaging and the detection of lymph node metastases in an animal model and to
      compare gadofluorine M with Gadomer (both, Schering, Berlin, Germany) for lymph
      node enhancement. MATERIALS AND METHODS: Enhancement of popliteal and iliac lymph
      nodes was studied in VX2 tumor-bearing rabbits before injection and at 5-120
      minutes and 24 hours after intravenous bolus injection of 0.025, 0.05, and 0.1
      mmol gadolinium per kilogram of body weight gadofluorine M (six rabbits) or 0.5
      mmol/kg Gadomer (eight rabbits). Effects of treatment and time point at
      enhancement were evaluated with repeated measures analysis of variance. Means
      were separated with all-pairs comparison with Tukey-Kramer adjustment. After 1.5
      T magnetic resonance (MR) imaging, lymph nodes were removed, and prepared
      sections were stained with hematoxylin-eosin for microscopic examination.
      RESULTS: MR images in VX2 tumor-bearing rabbits revealed rapid and strong signal
      intensity increase in the functional lymph node tissue by 15 minutes after
      intravenous injection of gadofluorine M. Maximum enhancement of 165%-309% was
      observed 60-90 minutes after injection (enhancement with 0.05 and 0.1 mmol/kg
      significantly different from that with 0.025 mmol/kg, P < or =.05). Metastatic
      tissue showed only slight enhancement at early time points, resulting in high
      contrast differentiation between functional and metastatic tissue. Intravenous
      injection of the blood-pool agent Gadomer induced only short and inhomogeneous
      lymph node enhancement (enhancement significantly lower [P < or =.05] than that
      with gadofluorine M). CONCLUSION: Findings in the study showed that gadofluorine
      M produces rapid lymph node accumulation. Diagnosis of lymph node metastases was
      shown with intravenous injection of gadofluorine M with a minimum effective
      diagnostic dose of 0.025 mmol/kg.

PMID- 15163807
TI  - Catheter-based in vivo imaging of enzyme activity and gene expression:
      feasibility study in mice.
AB  - PURPOSE: To construct and evaluate an interventional catheter-based imaging
      system for intravital monitoring of molecularly sensitive near-infrared
      fluorescent probes and optical marker genes. MATERIALS AND METHODS: An imaging
      device that was based on a miniaturized fiberoptic sensor (MIFS) was built in
      which images created with a 2.7-F fiberoptic catheter were relayed through a
      dichroic mirror, through a bandpass filter, and on two independent cameras. This
      system permitted simultaneous recording of white-light and fluorescent images.
      Spatial resolution, spectral transmissions, and sensitivity were determined in
      vitro. In vivo testing was performed in nude mice bearing intraperitoneal tumors
      that express green fluorescent protein and in a mouse model of ovarian carcinoma
      with enzyme-activatable near-infrared probes sensitive to tumoral protease
      activity. Signal intensity on images of tumors and that on images of normal
      tissue were measured and compared with t test. RESULTS: The catheter, which was
      advanced through an 18-gauge sheath, showed resolution of 7 line pairs per
      millimeter and detection limit for fluorochrome Cy5.5 of 1-10 pmol. Detection of
      endogenous green fluorescent protein gene expression was feasible in tumor
      nodules smaller than 1 mm in diameter (mean tumor signal intensity, 153.26 +/-
      26.45 [SD], compared with that of adjacent nontumoral tissue of 36.73 +/- 11.69;
      P <.008). Similarly, activation of the near-infrared probe by tumoral proteases
      could be detected in peritoneal tumor seeds of ovarian cancer model with mean
      tumor signal intensity of 246.33 +/- 7.77 compared with that of adjacent
      nontumoral tissue of 41.56 +/- 18.64 (P <.001). Mean contrast-to-noise ratio in
      the near-infrared channel exceeded white-light contrast-to-noise ratio by a
      factor of 6.7 (P <.02). CONCLUSION: With this system, in vivo MIFS imaging of
      gene expression, enzyme activity, and potentially other molecular events is
      feasible, through direct interventional access to several organs and body
      cavities and potentially through transvascular approaches.

PMID- 15163809
TI  - Transendocardial delivery of extracellular myocardial markers by using
      combination X-ray/MR fluoroscopic guidance: feasibility study in dogs.
AB  - PURPOSE: To demonstrate the feasibility of using a combination of x-ray
      fluoroscopic and magnetic resonance (MR) fluoroscopic (ie, x-ray/MR fluoroscopy)
      guidance for left ventricular (LV) catheterization and transendocardial delivery
      of extracellular tissue markers. MATERIALS AND METHODS: Experiments were
      performed in six dogs by using an x-ray/MR fluoroscopy system. The arterial guide
      wire and catheter were advanced into the heart with x-ray fluoroscopic guidance.
      The dogs were injected with 0.5, 1.0, and 2.0 mL of iohexol. For passive catheter
      tracking, a steady-state free precession MR imaging sequence was used. A
      steerable dual-lumen catheter was used to transendocardially inject a mixture of
      gadodiamide (0.05 mol/L) plus Evans blue dye (3%). An electrocardiographically
      gated dual-inversion-recovery MR imaging sequence was used to visualize the
      myocardial delivery of the gadodiamide-blue dye mixture. A high concentration of
      gadodiamide (0.5 mol/L) was used to demarcate the borders of the area of
      interest, or "hit the target." Blood pressure, heart rate, and oxygen saturation
      were measured before and after the intervention. Analysis of variance, Scheffe,
      and paired Student t tests were used for data analysis. RESULTS: LV
      catheterization via arterial access was feasible with two-dimensional x-ray
      fluoroscopic and three-dimensional MR fluoroscopic guidance. Delivery of the
      gadodiamide-blue dye mixture and the consequences of the procedure were monitored
      with MR imaging. Gadolinium-enhanced regions were bright on T1-weighted MR
      images, but they varied in size as a function of injectant volume. The mean sizes
      of these regions were 1.5% +/- 0.6 of the LV after the 0.5-mL injection of the
      mixture and 7.0% +/- 0.5 of the LV after the 2.0-mL injection (P <.001, Scheffe
      test). The corresponding mean sizes of the blue dye-enhanced regions were 2.3% +/
      0.6 and 8.3% +/- 0.4, respectively (P <.001). A high concentration of
      gadodiamide caused signal intensity loss around the gadolinium-enhanced regions.
      CONCLUSION: Transendocardial delivery of potential therapeutic solutions is
      feasible with x-ray/MR fluoroscopic guidance. The injection catheter can be
      navigated with MR imaging guidance to hit the target.

PMID- 15163810
TI  - Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.
AB  - PURPOSE: To investigate the feasibility of obtaining reproducible apparent
      diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory
      triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to
      investigate the sensitivity of ADC maps in the evaluation of renal blood flow,
      and to use this technique to monitor acute graft rejection in transplanted rat
      kidneys. MATERIALS AND METHODS: Spin-echo diffusion-weighted MR imaging
      measurements were performed in 20 normal rats and nine rats that had undergone
      transplantation (six rats had received allografts; three had received isografts)
      at 7 T. To evaluate the effect of alteration in blood flow and water transport
      function, angiotensin II was infused in six normal rats and a series of spin-echo
      diffusion-weighted MR images was obtained at five time points. Transplanted
      kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and
      gradient-echo MR images every 2 hours for 8 hours on postoperative day 4.
      Statistical analysis was performed with repeated-measures multivariate analysis
      of variance and the paired t test. RESULTS: No significant differences in ADC
      values were observed between right and left kidneys in all three orthogonal
      directions; however, a small difference was observed between the cortex and
      medulla. ADC values in the cephalocaudal and mediolateral directions were higher
      than those in the anteroposterior direction (P <.01 for all). ADC values in the
      cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin
      II-induced reduction in renal blood flow. No significant signal intensity change
      was observed between native and transplanted kidneys on gradient-echo MR images.
      Allografts exhibited decreased ADC values (P <.01) and isografts exhibited
      similar ADC values compared with native kidneys. CONCLUSION: These findings
      suggest that reproducible renal ADC maps can be obtained in rats by using spin
      echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR
      imaging may have potential as a noninvasive tool for monitoring early graft
      rejection after kidney transplantation.

PMID- 15163811
TI  - Chronic prostatitis: MR imaging and 1H MR spectroscopic imaging findings--initial
      observations.
AB  - PURPOSE: To determine whether chronic prostatitis affects three-dimensional
      proton magnetic resonance (MR) spectroscopic imaging in evaluation of disease in
      the peripheral zone. MATERIALS AND METHODS: Combined MR imaging and three
      dimensional MR spectroscopic imaging data were examined retrospectively in 12
      patients with radical prostatectomy specimens that contained regions of chronic
      prostatitis larger than 6 mm in the peripheral zone. The 6-mm restriction was
      based on MR spectroscopic imaging spatial resolution of 6.25 mm. Transverse T2
      weighted MR images were reviewed for changes in signal intensity (SI): normal,
      suspicious for cancer (nodular focal low SI), or indeterminate (focal low SI that
      was not nodular or contour deforming or diffuse low SI). At MR spectroscopic
      imaging, proton spectra were considered suspicious for cancer if the ratio of
      choline plus creatine to citrate was more than 2 SDs above normal mean peripheral
      zone values. RESULTS: In the 12 patients, mean pretreatment prostate-specific
      antigen level was 5.77 +/- 2.07 (SD), and median biopsy Gleason score for the
      gland was 6. At MR imaging in the area of histopathologically confirmed chronic
      prostatitis, seven of 12 patients had focal low SI that was not nodular (contour
      deforming) over a region in and around the pathologically defined focus of
      chronic prostatitis. MR imaging in one patient showed diffuse low SI that
      correlated with a diffuse area of chronic prostatitis at pathologic examination.
      MR imaging in another patient showed nodular focal low SI that was suspicious for
      cancer and corresponded to a focus of chronic prostatitis at pathologic
      examination. The remaining three patients had no MR imaging abnormality in the
      region of chronic prostatitis. In the pathologically identified regions of
      chronic prostatitis, MR spectroscopic imaging data in nine of 12 patients
      demonstrated elevated choline peak and reduced or no citrate, findings that mimic
      those of cancer. In two patients, the spectra were normal, and in the remaining
      patient, the spectra were nondiagnostic. CONCLUSION: At MR spectroscopic imaging,
      pathologically confirmed chronic prostatitis may demonstrate metabolic
      abnormality that leads to false-positive diagnosis of cancer. The most common MR
      imaging finding in chronic prostatitis was focal low SI that was not specific for
      cancer. In one patient, the MR imaging diagnosis of cancer could not be excluded.

PMID- 15163812
TI  - Uniform vascular contrast enhancement and reduced contrast medium volume achieved
      by using exponentially decelerated contrast material injection method.
AB  - PURPOSE: To investigate in computed tomographic (CT) angiography whether an
      exponentially decelerated contrast medium injection, as compared with a standard
      constant-rate injection, can facilitate uniform vascular contrast enhancement
      with a reduced contrast material volume. MATERIALS AND METHODS: CT angiography of
      the abdominal aorta was performed in 46 subjects by using an exponentially
      decelerated injection method: 134 mL of contrast medium was injected for 40
      seconds, starting at 4.0 mL/sec and decreasing exponentially to 2.7 mL/sec by the
      end of the injection. Twenty-one of these subjects also underwent CT angiography
      with a constant-rate injection: 160 mL of contrast medium was injected for 40
      seconds at a constant rate of 4 mL/sec. Time-enhancement curves and the magnitude
      of peak vascular enhancement were measured. Enhancement uniformity was evaluated
      by using three indexes: (a) duration of contrast enhancement achieved within 80%
      of the peak (80% DCE), (b) SD of the normalized contrast enhancement (SDNCE)
      measured from the beginning of spiral CT scanning to the time when the
      enhancement decreased to a level lower than the beginning level, and (c) slope of
      the enhancement curve calculated by using linear regression analysis. RESULTS:
      Exponentially decelerated injection resulted in more uniform enhancement. Mean
      values generated by using exponentially decelerated versus constant-rate
      injection in 21 paired comparisons were, respectively, 30.8 seconds +/- 5.0
      versus 22.6 seconds +/- 7.6 for 80% DCE, 0.052 +/- 0.017 versus 0.086 +/- 0.031
      for SDNCE, and 0.47 HU/sec +/- 0.70 versus 2.27 HU/sec +/- 0.87 for slope (P
      <.001 for all indexes). Compared with the peak enhancement resulting from the
      constant-rate injection, that resulting from the exponentially decelerated
      injection was reduced by a mean of 17.2% +/- 10.0. CONCLUSION: Uniform vascular
      contrast enhancement and reduced contrast medium volume, which are desirable in
      CT angiography, can be achieved with exponentially decelerated injection.

PMID- 15163813
TI  - Quantitative analysis of focal masses at MR imaging: a plea for standardization.
AB  - PURPOSE: To assess the effects of changing analytic method variables on the
      signal intensity (SI) difference-to-noise ratios (SDNRs) for the contrast between
      lesions and background organs depicted on magnetic resonance (MR) images and to
      propose a standardized analytic method for the quantitative analysis of focal
      masses seen at MR imaging. MATERIALS AND METHODS: The SIs of 48 liver metastases
      (originating from colorectal cancer) in 20 patients, the surrounding liver
      parenchyma, and the background noise were measured on T2-weighted MR images. All
      2000 and 2001 issues of the American Journal of Roentgenology, the Journal of
      Magnetic Resonance Imaging, Magnetic Resonance Imaging, and Radiology were
      searched for articles describing quantitative analyses. SDNRs were calculated by
      using formulas from these articles and various region-of-interest (ROI) locations
      to measure metastasis and background noise SIs. The Wilcoxon signed rank test was
      used to compare the various SDNR calculations. RESULTS: In 34 articles in which
      quantitative analyses of focal masses are described, the reported SDNRs were
      calculated with four different formulas. The SDNRs for our study material
      calculated with the four formulas reported in the literature differed grossly in
      both number and unit. The SDNRs for ROIs encompassing the entire metastasis
      differed significantly (P =.034) from the SDNRs for ROIs in a homogeneous area of
      the metastasis margin. Differences in SDNRs between various noise ROI locations
      were significant (P <.022). CONCLUSION: Slight changes in the variables of
      quantitative analysis of focal masses had marked effects on reported SDNRs. To
      overcome these effects, the use of a standardized method involving one formula, a
      lesion ROI in a homogeneous area at the metastasis margin, and a background noise
      ROI along the phase-encoding axis in the air (including systematic noise) is
      proposed for the quantitative analysis of findings on magnitude MR images.

PMID- 15163815
TI  - Case 71: Ebstein anomaly.

PMID- 15163816
TI  - Normal anatomy and complications after gastric bypass surgery: helical CT
      findings.
AB  - PURPOSE: To determine the usefulness and potential pitfalls of helical computed
      tomography (CT) for depiction of normal anatomy and diagnosis of complications
      after gastric bypass surgery. MATERIALS AND METHODS: From March 1998 to July
      2002, 100 abdominal and pelvic CT examinations were performed in 72 patients
      after gastric bypass surgery for treatment of morbid obesity. Two of four
      attending abdominal radiologists retrospectively assessed the CT images in
      consensus for normal postoperative gastrointestinal anatomy and complications
      such as leaks, staple line dehiscence, bowel obstruction, abscess, hepatic or
      splenic infarction, and hernia. CT findings were compared with clinical,
      surgical, and other imaging findings. RESULTS: The gastric pouch, excluded
      stomach, proximal efferent loop, oversewn jejunal loop, and distal jejunojejunal
      anastomosis were identified in 96 (96%) of 100 studies and 69 (96%) of 72
      patients, 100 (100%) of 100 studies and 72 (100%) of 72 patients, 99 (99%) of 100
      studies and 71 (99%) of 72 patients, 88 (88%) of 100 studies and 61 (85%) of 72
      patients, and 67 (67%) of 100 studies and 46 (64%) of 72 patients, respectively.
      The fundus of the excluded stomach was filled with a combination of air, fluid,
      and contrast material, which mimicked a loculated fluid collection in 15 (15%) of
      100 studies and 13 (18%) of 72 patients. Sixty-two abnormalities, detected in 41
      patients, included leak (n = 12), loculated fluid collection unrelated to leak (n
      = 9), markedly distended excluded stomach (n = 6), small-bowel obstruction (n =
      6), gastric staple line dehiscence (n = 6), splenic infarction (n = 5), hematoma
      (n = 5), left hepatic lobe infarction (n = 3), and hernia related to gastric
      bypass (n = 10, including three internal hernias, three incisional hernias, and
      four nonincisional ventral hernias). Seventeen patients required a total of 21 CT
      guided interventional procedures. CONCLUSION: Helical CT is useful for
      identifying normal postoperative anatomy and complications after gastric bypass
      surgery.

PMID- 15163817
TI  - Positional change in colon polyps at CT colonography.
AB  - PURPOSE: To determine the frequency with which polyps change positions with
      respect to the bowel surface and the cause of this movement. MATERIALS AND
      METHODS: From December 2001 to March 2003, 113 patients underwent computed
      tomographic (CT) colonography prior to colonoscopy. For all confirmed polyps that
      were 5 mm and larger, images obtained with CT colonography were retrospectively
      analyzed by one author to determine if the polyp was present on both data sets or
      on only one data set. Retrospective evaluation of these polyps for ventral or
      dorsal location within the colonic lumen was performed for data sets obtained
      with patients in the prone and the supine position. The data sets were further
      reviewed by another author to determine the cause of positional change, when
      present. RESULTS: Twenty-six patients had a total of 49 histologically proved
      colorectal polyps that were 5 mm and larger. Eight of 49 colorectal polyps were
      depicted only on images obtained with the patient in the supine or prone
      position. Of the remaining 41 polyps that were depicted on images obtained with
      the patient in the supine and the prone position, 11 moved from a dorsal to a
      ventral location or vice versa relative to the colonic surface when the patient
      changed position. Five of these polyps were pedunculated on a stalk. Six were
      sessile; two were located in the sigmoid colon, two in the transverse colon, one
      in the ascending colon, and one in the cecum. In these cases, polyp mobility was
      related to positional changes of the colon in the mesentery, as opposed to true
      mobility of the polyp. CONCLUSION: In this series, 27% of polyps moved from a
      ventral location to a dorsal location relative to the colonic surface when the
      patient was turned from the supine to the prone position; thus, polyps appeared
      to be mobile. Thus, a mobile filling defect cannot be assumed to be residual
      fecal material at CT colonography.

PMID- 15163818
TI  - The ankle teardrop sign.

PMID- 15163819
TI  - Glenohumeral deformity in children with internal rotation contractures secondary
      to brachial plexus birth palsy: intraoperative arthrographic classification.
AB  - PURPOSE: To evaluate, with intraoperative arthrography, joint morphology in
      children undergoing surgical treatment of residual paralysis of the shoulder
      resulting in brachial plexus birth palsy and to correlate the morphology with the
      degree of passive external rotation. MATERIALS AND METHODS: In 64 children (age
      range, 7 months to 13 years 6 months), an orthopedic surgeon performed
      intraoperative arthrography and measured passive external rotation while the
      patient received a general anesthetic. The orthopedic surgeon and three
      radiologists reviewed arthrograms and in consensus classified glenohumeral joints
      in one of four categories: concentric, with the humeral head well centered on the
      glenoid fossa; flat, with flattening of the posterior glenoid; biconcave, with
      the humeral head in articulation with the posterior of two concavities, which
      were in the same plane; and pseudoglenoid, with the humeral head in articulation
      with the more posterior of two concavities, with retroversion and in a plane
      different from that of the anterior concavity. Kruskal-Wallis test was used to
      compare preoperative external rotation with four appearances of glenoid. RESULTS:
      Twenty-one children had concentric glenohumeral joints; seven children, flat
      glenohumeral joints; 19 children, biconcave glenoid; and 17 children,
      pseudoglenoid. Median passive external rotation was -20 degrees for patients with
      pseudoglenoid, -10 degrees for those with flat or biconcave glenoids, and 0
      degrees for those with concentric glenoids. Presence and type of glenoid
      deformity were significantly associated with severity of internal rotation
      contracture (P <.001). CONCLUSION: Consistent patterns of glenohumeral joint
      deformity in brachial plexus birth palsy were identified and correlated with
      severity of internal rotation contracture.

PMID- 15163820
TI  - Effect of smoking on restenosis during the 1st year after lower-limb endovascular
      interventions.
AB  - PURPOSE: To investigate whether smoking has an effect on recurrent lumen
      narrowing after percutaneous transluminal angioplasty (PTA) or stent placement in
      lower-limb arteries. MATERIALS AND METHODS: A total of 650 patients (median age,
      70 years; 389 men) with peripheral artery disease who underwent iliac artery PTA
      (n = 95), iliac artery stent placement (n = 83), femoropopliteal PTA (n = 406),
      or femoropopliteal stent placement (n = 66) were selected from a prospective
      database. Patients were categorized according to their preintervention smoking
      habits as nonsmokers (n = 352), light smokers (one to nine cigarettes daily) (n =
      54), habitual smokers (10-20 cigarettes daily) (n = 82), or heavy smokers (>20
      cigarettes daily) (n = 162). Multivariate Cox proportional hazards analysis was
      used to determine whether there was an association between smoking habits and
      restenosis (> or =50%) in the treated vessel segment within 1 year after
      treatment. RESULTS: Cumulative restenosis rates at 6 and 12 months according to
      patients' smoking habits were 99 and 190 nonsmokers, 18 and 22 light smokers, 16
      and 29 habitual smokers, and 26 and 47 heavy smokers, respectively (P <.001).
      Adjusted hazard ratios for restenosis in smokers compared with nonsmokers were
      1.51 (95% CI: 0.92, 2.50) for light smokers, 0.49 (95% CI: 0.28, 0.87) for
      habitual smokers, and 0.46 (95% CI: 0.30, 0.71) for heavy smokers, indicating a
      reduced restenosis risk in patients who smoked 10 or more cigarettes daily. These
      patients had reduced restenosis rates after either iliac (P =.011) or
      femoropopliteal intervention (P =.009). However, endovascular treatment at a
      younger age, coronary artery disease, and history of myocardial or
      cerebrovascular infarction were more frequently found in smokers. CONCLUSION:
      Smoking 10 or more cigarettes daily is associated with a reduced rate of
      intermediate-term restenosis after lower-limb endovascular interventions.

PMID- 15163821
TI  - Pancreas transplants: experience with 232 percutaneous US-guided biopsy
      procedures in 88 patients.
AB  - PURPOSE: To retrospectively assess the authors' experience with percutaneous
      ultrasonographic (US)-guided biopsy of pancreas transplants. MATERIALS AND
      METHODS: Data from 232 percutaneous US-guided pancreas transplant biopsies
      performed in 88 patients were retrospectively reviewed. Biopsies were typically
      performed on an outpatient basis by using local anesthesia. Considerations
      included the indication for the biopsy, the type of pancreas transplant, the
      number of needle passes, the size of the biopsy needle, the use of aspirin, and
      the success of the biopsy. Important complications were detailed. RESULTS: Of the
      232 biopsies performed, 78 were for clinically indicated reasons and 154 were for
      surveillance purposes. The number of biopsy procedures per patient ranged from
      one to nine (mean, 2.6). Two needle passes were performed in 196 (84.5%) of the
      biopsy procedures. Almost all biopsies (ie, 228 [98.3%]) were performed by using
      an 18-gauge biopsy device. Adequate pancreatic tissue was obtained in 223 (96.1%)
      of the procedures. One hundred sixty-seven biopsies (72.0%) were performed while
      patients were receiving therapeutic aspirin. Six biopsies (2.6%) resulted in
      clinically important complications: three cases of intraabdominal hemorrhage and
      one case each of gross hematuria, allograft pancreatitis, and severe pain
      requiring overnight hospitalization. Two of the four bleeding complications
      occurred while patients were receiving therapeutic aspirin. CONCLUSION: US-guided
      biopsy of pancreas transplants yielded tissue that was adequate more than 96% of
      the time. Important complications in this study were few (2.6%) and did not
      appear to be related to aspirin use.

PMID- 15163822
TI  - Lung tumor growth: assessment with CT--comparison of diameter and cross-sectional
      area with volume measurements.
AB  - PURPOSE: To compare diameter and cross-sectional area measurements with volume
      measurements in the assessment of lung tumor growth with serial computed
      tomography (CT). MATERIALS AND METHODS: Patients with lung cancer who underwent
      at least one pair of chest CT examinations 25 or more days apart before treatment
      and with a tumor size of T1 (< or =3-cm diameter) at the initial CT examination
      were identified. A total of 63 patients (62 men, one woman) who underwent 93
      pairs of CT examinations were included. Images obtained at each examination were
      displayed, and the maximum diameter, cross-sectional area, and volume of the
      tumor were measured. For each measurement, the change between examinations was
      assessed to determine whether the change reached a detection threshold for
      growth, as determined in a prior study with simulated tumors. Results were then
      compared between measurement methods, with volume change serving as the reference
      standard, by calculating Spearman rank-order coefficients between examinations.
      Tumor size or section width were also evaluated with the two-tailed Fisher exact
      probability test to determine if they affected agreement about tumor growth
      between measurement methods. RESULTS: Thresholds were as follows: diameter, 2.1
      mm with hand-held calipers and 0.68 mm with electronic calipers; area, 9.4%;
      volume, 16.5%. The median time between examinations was 92 days (range, 25-1,221
      days). Median diameter increased from 19.3 mm to 23.0 mm (19.2%), median area
      from 207 mm(2) to 267 mm(2) (29.0%), and median volume from 1,652 mm(3) to 2,443
      mm(3) (47.9%). Growth assessment with these diameter (as assessed with hand-held
      and electronic calipers) and area thresholds disagreed with those obtained with
      volume in 34 (37%), 26 (28%), and 25 (27%) of the 93 pairs of CT examinations,
      respectively. Of diameter assessments with the hand-held caliper threshold, 28
      (30%) were false-negative; false-negative results occurred with this diameter
      threshold and area threshold with examination intervals as long as 1 year.
      CONCLUSION: Growth assessment of T1 lung tumors on serial CT scans with
      nonvolumetric measurements frequently disagrees with growth assessment with
      volumetric measurements.

PMID- 15163823
TI  - Metastases in mediastinal and hilar lymph nodes in patients with non-small cell
      lung cancer: quantitative and qualitative assessment with STIR turbo spin-echo MR
      imaging.
AB  - PURPOSE: To evaluate short inversion time inversion-recovery (STIR) turbo spin
      echo (TSE) magnetic resonance (MR) imaging for detection of metastases in lymph
      nodes by using quantitative and qualitative analyses. MATERIALS AND METHODS: One
      hundred ten patients (68 men and 42 women) with non-small cell lung cancer who
      ranged in age from 36 to 82 years (mean age, 64 years) were examined with
      respiratory-triggered STIR TSE MR imaging. Ratios of signal intensity in a lymph
      node to that in a 0.9% saline phantom (lymph node-saline ratios [LSRs]) for all
      lymph nodes were classified into three groups according to nodal short-axis
      diameter. LSRs of each group were compared by using pathologic diagnosis as the
      standard of reference. For quantitative analysis, the LSR threshold value for a
      positive test was determined on a per-node basis and tested for ability to enable
      a correct diagnosis on a per-patient basis. For qualitative analysis, signal
      intensities of lymph nodes were assessed by using a five-point visual scoring
      system. Results of quantitative and qualitative analyses were compared on a per
      patient basis with McNemar testing. RESULTS: In 110 patients, 92 of 802 lymph
      nodes were pathologically diagnosed as containing metastases, while 710 lymph
      nodes did not contain metastases. Mean LSR in the lymph node group with
      metastasis was higher than that in the group without metastasis (P <.05). When an
      LSR of 0.6 was used as the positive-test threshold at quantitative analysis,
      sensitivity was 93% (37 of 40 patients) and specificity was 87% (61 of 70
      patients) on a per-patient basis. With a score of 4 as the positive-test
      threshold at qualitative analysis, sensitivity was 88% (35 of 40 patients) and
      specificity was 86% (60 of 70 patients) on a per-patient basis. There was no
      significant difference (P >.05) between results of quantitative and those of
      qualitative analysis. CONCLUSION: Quantitative and qualitative analyses of STIR
      TSE MR images enable differentiation of lymph nodes with metastasis from those
      without. Qualitative analysis can substitute for quantitative analysis of STIR
      TSE MR imaging data.

PMID- 15163824
TI  - On improving temporal and spatial resolution of 3D contrast-enhanced body MR
      angiography with parallel imaging.
AB  - Use of a parallel imaging technique to improve temporal and spatial resolution at
      three-dimensional contrast-enhanced magnetic resonance (MR) angiography was
      investigated. Thirty experiments were performed in five groups of healthy
      subjects. In groups 1-3, the technique was used to improve imaging speed by a
      factor of two or four while maintaining spatial resolution. Contrast agent
      concentration was two to four times higher than at standard MR angiography, to
      take advantage of the faster imaging speed. In groups 4 and 5, the technique was
      used to double spatial resolution in the phase-encoding direction while
      maintaining imaging speed and contrast agent concentration. At a two to four
      times faster imaging speed, signal-to-noise ratio (SNR) and contrast-to-noise
      ratio (CNR) almost equaled those at standard MR angiography, likely a result of
      increased contrast agent concentration. The use of parallel imaging to achieve
      higher spatial resolution was also proved feasible, but with substantial
      reduction in SNR and CNR.

PMID- 15163825
TI  - Proteoglycan loss in human knee cartilage: quantitation with sodium MR imaging-
      feasibility study.
AB  - The feasibility of using sodium magnetic resonance (MR) imaging to detect
      proteoglycan loss in early-stage osteoarthritis is evaluated. Fixed charge
      density (FCD) maps were calculated from sodium MR imaging data collected in nine
      healthy volunteers and three individuals with symptoms of early-stage
      osteoarthritis by using a 4.0-T clinical MR imaging unit. Data from the healthy
      individuals revealed a mean FCD of -182 mmol/L +/- 9. Data from the symptomatic
      subjects revealed focal regions of decreased FCD, with mean values ranging from 
      108 to -144 mmol/L, indicating proteoglycan loss from the cartilage matrix. The
      data suggest that sodium MR imaging has potential for use as a quantitative
      diagnostic tool to measure changes in proteoglycan content in early-stage
      osteoarthritis.

PMID- 15163826
TI  - Nasopharyngeal carcinoma tumor volume measurement..
AB  - Tumor volume was measured in 69 patients with nasopharyngeal carcinoma. On
      transverse nonenhanced T1-weighted and gadolinium-enhanced T1-weighted magnetic
      resonance (MR) images, segmentation was performed by means of seed growing and
      knowledge-based fuzzy clustering methods. Data were compared with those collected
      with the manual tracing method and analyzed for interoperator variance and
      interobserver reliability. There was no significant difference between the
      volumes determined with manual tracing or semiautomated segmentation (P >.05). On
      the volume level, Pearson correction coefficients were close for both the manual
      tracing and semiautomated methods. Significant differences in interoperator
      variance existed between the two methods on the pixel level (P <.05). Compared
      with manual tracing, the semiautomated method helped reduce interoperator
      variance and obtain higher interobserver reliability. Findings in the current
      study validate the use of semiautomated volume measurement methods for
      nasopharyngeal carcinoma.

PMID- 15163827
TI  - Further thoughts on low-level radiation: an evolutionary biologist's perspective.

PMID- 15163828
TI  - Embolization of uterine arteries with type IA utero-ovarian anastomoses.

PMID- 15163829
TI  - Contrast-enhanced coronary MR angiography.

PMID- 15163830
TI  - C sign comments.

PMID- 15163831
TI  - Biases likely invalidate the conclusions.

PMID- 15163832
TI  - Spinal mobility in ankylosing spondylitis: reliability, validity and
      responsiveness.
AB  - OBJECTIVE: To evaluate the measurement properties of an evidence-based selection
      of measures of spinal mobility in patients with ankylosing spondylitis (AS).
      METHODS: Measurements of spinal mobility were taken by trained observers within a
      UK rheumatology centre. Inter-observer reliability was assessed. Intra-observer
      reliability was assessed in patients reporting no change in AS-specific health at
      2 weeks. Validity was assessed and scores were correlated with responses to
      health transition questions. Responsiveness was evaluated for patients reporting
      change in health at 6 months. RESULTS: Reliability estimates support the use of
      all measures in individual evaluation (intraclass correlation>0.90). Correlations
      between measures of spinal mobility were in the hypothesized direction; the
      largest was between the modified Schober index (15 cm) (MSI) and the other
      measures. As hypothesized, small to moderate levels of correlation were found
      between mobility measures and patient-assessed health status. There was no
      significant linear relationship between mobility measures and self-reported
      health transition. Fingertip-to-floor distance following trunk forward flexion
      (FFD) was the most responsive mobility measure but was not as responsive as two
      AS-specific patient-assessed instruments, the Ankylosing Spondylitis Quality of
      Life Questionnaire (ASQoL) and the Bath Ankylosing Spondylitis Disease Activity
      Index (BASDAI). The MSI and cervical rotation (Crot) also had evidence of
      responsiveness. Low levels of responsiveness were found for the remaining
      measures. CONCLUSION: All mobility measures had adequate levels of reliability
      and validity. The MSI had a strong relationship with all mobility measures, and
      the FFD and Crot were the most responsive to self-perceived changes in health at
      6 months. The MSI, FFD and Crot are recommended for clinical practice and
      research.

PMID- 15163833
TI  - The historical development of thermal imaging in medicine.

PMID- 15163834
TI  - Urinary matrix metalloproteinase-9 and interleukin-6 and renal manifestations of
      primary Sjogren's syndrome.

PMID- 15163835
TI  - A case of distal renal tubular acidosis (type 1) presenting with musculoskeletal
      pain.

PMID- 15163836
TI  - Post-partum polyarthritis associated with a staphylococcal breast abscess.

PMID- 15163837
TI  - Rosai-Dorfman disease masquerading as chronic ankle arthritis: a case report and
      review of the literature.

PMID- 15163840
TI  - The FUTURE of ErbB-1 and ErbB-2 pathway inhibition in breast cancer: targeting
      multiple receptors.

PMID- 15163841
TI  - Monoclonal antibodies, small molecules, and vaccines in the treatment of breast
      cancer.
AB  - The human epidermal growth factor receptor (HER, ErbB) family of receptors is
      considered an important therapeutic target, and various types of molecularly
      based small molecules, including monoclonal antibodies, protein tyrosine kinase
      inhibitors, and therapeutic vaccines, are in development as potential therapies
      for metastatic breast cancer. Trastuzumab (Herceptin; Genentech, Inc.; South San
      Francisco, CA), the first approved monoclonal antibody for HER-2 (ErbB-2)
      overexpressing metastatic breast cancer, provided the proof of principle that
      targeting specific receptors results in clinical benefit. Other monoclonal
      antibodies and the small molecule dual protein tyrosine kinase inhibitors show
      great promise as treatments for metastatic breast cancer but require evaluation
      in clinical trials to assess their benefits. Therapeutic vaccines may have a
      role, particularly in early-stage disease, but they are associated with greater
      limitations and study design issues that make their evaluation difficult. Optimum
      combination therapy regimens with a variety of novel approaches that incorporate
      small molecule targeted therapies need to be developed, and the population most
      likely to benefit from targeted therapies needs to be identified.

PMID- 15163842
TI  - Dual kinase inhibition in the treatment of breast cancer: initial experience with
      the EGFR/ErbB-2 inhibitor lapatinib.
AB  - Dual inhibition of ErbB-1 (EGFR) and ErbB-2 (HER-2) tyrosine kinases has been
      found to exert greater biologic effects in the inhibition of signaling pathways
      promoting cancer cell proliferation and survival than inhibition of either
      receptor alone. The novel dual EGFR/ErbB-2 tyrosine kinase inhibitor lapatinib
      (GlaxoSmithKline; Research Triangle Park, NC) has been shown to inhibit tumor
      cell growth in vitro and in xenograft models for a variety of human tumors.
      Preliminary findings in a phase I study of lapatinib in patients with solid
      tumors indicate doses up to 1,800 mg per day are well tolerated. No grade 4
      toxicities were observed and only two of 43 patients had grade 3 toxicity
      (diarrhea). Clinical activity of lapatinib was observed in these patients; nine
      patients with a variety of tumors remained on study for > or =4 months, one with
      a complete response (head and neck cancer). In a phase IB study in pretreated
      metastatic cancer patients with disease that could be biopsied, grade 1 or 2
      diarrhea and rash were the most common adverse events. Three patients with breast
      cancer refractory to trastuzumab (Herceptin; Genentech, Inc.; South San
      Francisco, CA) had partial responses and 12 patients with a variety of tumors had
      stable disease. Assessment of biologic correlates in these patients indicates
      that increased tumor cell apoptosis on the terminal deoxynucleotide transferase
      mediated dUTP nick-end labeling assay correlates with clinical response.
      Lapatinib currently is being evaluated in phase II and phase III trials in
      patients with metastatic breast cancer.

PMID- 15163843
TI  - The role of ErbB inhibitors in trastuzumab resistance.
AB  - The ErbB family of receptors and ligands is a complex, delicately balanced system
      involved in the growth and differentiation of normal human cells as well as
      neoplasms. Targeting this system with therapies that inhibit ErbB receptor
      activity in cancer patients has been somewhat successful, but resistance to ErbB
      inhibitor monotherapy is substantial. An understanding of the biology of ErbB
      receptor inhibitors is necessary to determine how best to utilize them in
      treatment regimens. Experimental evidence has provided valuable insights
      regarding mechanisms involved in resistance, and indicates that resistance can be
      reversed in some models. Ongoing studies in patients are evaluating whether
      agents that target both the epidermal growth factor (EGFR, ErbB-1) and ErbB-2
      (HER-2) receptors can prevent or delay resistance in patients with metastatic
      breast cancer that overexpresses HER-2. With a better understanding of the
      biology of breast cancer, and with several novel ErbB receptor inhibitors in
      development, continued progress for improved patient outcomes is expected.

PMID- 15163844
TI  - Overcoming endocrine therapy resistance by signal transduction inhibition.
AB  - Endocrine therapy is the most effective systemic treatment for patients with
      hormone-receptor-positive (HR(+)) breast cancer. Unfortunately, efficacy is often
      limited by the onset of resistance, which is almost inevitable for patients with
      advanced disease. Several patterns of endocrine resistance are recognizable
      clinically, including: A) tumors that are inherently insensitive to all attempts
      at estrogen receptor (ER) targeting despite expression of ER (pan-endocrine
      therapy resistance); B) tumors that are estrogen dependent but resistant to one
      or more specific endocrine therapies (agent-selective resistance); and C) tumors
      that initially respond but subsequently progress (acquired resistance). Current
      insights into the molecular basis for these resistance patterns are rudimentary,
      but are most clearly illuminated by investigations that focus on the crosstalk
      between the ErbB or HER peptide growth factor family and the ER. The data are
      sufficiently compelling to be addressed by ongoing clinical trials that examine
      combinations of endocrine agents and either trastuzumab (Herceptin; Genentech,
      Inc.; South San Francisco, CA) or ErbB-specific tyrosine kinase (TK) inhibitors.
      Preliminary data from a small "proof of concept" phase II study of letrozole
      (Femara; Novartis Pharmaceuticals Corporation; East Hanover, NJ) and trastuzumab
      demonstrated durable responses despite tamoxifen (Nolvadex; AstraZeneca
      Pharmaceuticals; Wilmington, DE) resistance. Efficacy was variable, however,
      despite the selection of patients on the basis of ER and ErbB-2 coexpression.
      Complicating matters further, resistance often occurs in the absence of any
      evidence for ErbB TK family member expression. In the absence of a clear target,
      common downstream signal transduction proteins that are known to intersect with
      the ER pathway can be inhibited to address resistance, including G proteins with
      farnesyltransferase inhibitors and molecular target of rapamycin (mTOR) with
      rapamycin analogues. With a number of phase III clinical trials now under way,
      major advances in the endocrine treatment of advanced disease are possible.

PMID- 15163845
TI  - A life of fusion.

PMID- 15163846
TI  - Merging routes.

PMID- 15163847
TI  - Symphony of errors.

PMID- 15163848
TI  - Declining immunity with age in the wild.
AB  - Despite their higher metabolic rates and lifetime energy expenditures, birds
      generally outlive similar-sized mammals even in the wild, often reaching maturity
      and aging considerably more slowly. Wild populations of many bird species have
      been monitored for years using banding-and-recapture methods, allowing field
      ornithologists to document age-related declines in survival and reproductive
      success. Although elderly birds rarely reach advanced stages of senescence in
      nature, many show other signs of physiological deterioration. In this
      Perspective, we review recent reports of aging-related changes in the immune
      response of two small European songbirds, the barn swallow and the collared
      flycatcher. Researchers in both studies challenged birds' humoral immune response
      by administering antigen to free-ranging adults during the breeding season. Older
      barn swallows--particularly breeding females--showed lower antibody responses
      (both primary and secondary) to vaccination with Newcastle disease virus, an
      avian pathogen. In flycatchers, older females raised lower antibody titers than
      younger breeders did in response to an injection of sheep red blood cells, a
      nonpathogenic antigen, and produced offspring with lower average body masses.
      Although the relevance of such measures of "immunosenescence" to actual fitness,
      reproductive success, and mortality is still unclear, studies of wild vertebrate
      populations may ultimately provide an important link between laboratory research
      and our understanding of the natural history and evolution of basic mechanisms of
      aging.

PMID- 15163849
TI  - GEHA--the pan-European "Genetics of Healthy Aging" project.
AB  - The pan-European "Genetics of Healthy Aging" (GEHA) consortium is undertaking a
      large study of long-lived individuals, which officially began on 22 May 2004. The
      consortium aims to identify genes that promote longevity and good health during
      the process of aging. The project will involve scientists working in multiple
      disciplines and using a variety of techniques.

PMID- 15163850
TI  - Surfactant-based methods for prevention of protein adsorption in capillary
      electrophoresis.
AB  - Surfactants such as didodecyldimethyl ammonium bromide (DDAB) and 1,2-dilauroyl
      sn-phosphatidylcholine (DLPC) form bilayers at the walls of bare silica
      capillaries. Once formed, these bilayers are stable in the absence of surfactant
      in the buffer. DDAB provides a cationic bilayer coating which yields a strong
      reversed EOF and is effective for separation of cationic proteins. DLPC provides
      a zwitterionic bilayer coating which is effective for both cationic and anionic
      proteins. The electroosmotic flow (EOF) is strongly suppressed in DLPC-coated
      capillaries, thus low mobility proteins are slow to elute, and so the coating is
      favored for separation of high mobility proteins.

PMID- 15163851
TI  - Capillary coating for protein separation based on Si-O and Si-C covalent bond
      formation for capillary electrophoresis with laser-induced fluorescence
      detection.
AB  - Protein adsorption to capillary walls is one of the major complications in
      protein analyses with capillary electrophoresis (CE). Coating the capillary with
      different materials is used to reduce the adsorption. This chapter overviews
      different approaches used for capillary coating and concentrates on those
      utilizing Si-O and Si-C covalent bonds. The apparatus and methods are presented
      for capillary coating using Si-O and Si-C chemistry. Furthermore, procedures are
      described for monitoring the quality of coating.

PMID- 15163852
TI  - On-column labeling reaction for analysis of protein contents of a single cell
      using capillary electrophoresis with laser-induced fluorescence detection.
AB  - This chapter presents methods for capillary electrophoresis (CE) fingerprinting
      of proteins in a cell extract and in single cells. A custom-made CE instrument
      with laser-induced fluorescence (LIF) detection, used for the analyses, is
      described. Detailed procedures are given for: (1) on column labeling of proteins
      with a fluorogenic reagent, 5-furoyl quinoline-3-carboxaldehyde, (2) CE
      separation of labeled proteins, (3) preparation of a protein extract from
      cultured cells, and (4) manipulations associated with analyses of proteins in
      single cells. More than 20 relevant publications are cited in this chapter to
      assist the reader with adopting the presented methods.

PMID- 15163853
TI  - Covalent and noncovalent labeling schemes for near-infrared dyes in capillary
      electrophoresis protein applications.
AB  - Capillary electrophoresis (CE) is experiencing increased use in the field of
      separation science. Part of its growing popularity of capillary electrophoresis
      can be attributed to the high efficiency of the separations achievable with the
      technique, making it an attractive tool for bioanalytical applications. Laser
      induced fluorescence (LIF) is a common detection method for CE. One of the
      problems frequently experienced when using visible LIF detection is matrix
      autofluorescence which has the effect of degrading the overall sensitivity of the
      technique. However, the use of near-infrared (NIR) laser induced fluorescence
      nearly eliminates matrix autofluorescence, as very few molecules have intrinsic
      fluorescence in this region. This chapter describes the use of covalent and
      noncovalent labeling schemes for tagging biomolecules with near infrared dyes. To
      fully appreciate the advantages that the NIR LIF technique can supply, we also
      review applications that employ detection schemes other than NIR LIF. Specific
      applications to be discussed include drug-protein studies by CE, as well as
      capillary electrophoretic immunoassays.

PMID- 15163854
TI  - Capillary electrophoresis in the analysis and monitoring of biotechnological
      processes.
AB  - Capillary electrophoresis (CE) became a versatile technique for analysis of
      biological macromolecules. We have applied capillary zone electrophoresis (CZE)
      and SDS-gel CE for the characterization of recombinant proteins during
      development of major bioprocessing steps, including fermentation, hybridoma cell
      cultivation, chromatographic purification, and chemical transformation. Rapid SDS
      gel CE was developed for the fast analysis of fermentation broth and hybridoma
      cell culture. The total analysis time was reduced to 4.5 min. We have developed
      system for fraction collection, which allows analyzing separated proteins by
      MALDI-TOF-MS. The main advantages of applied techniques were high resolution and
      selectivity, fast analysis, and high accuracy.

PMID- 15163855
TI  - Capillary electrophoresis of proteins in a quality control environment.
AB  - A method for determining the purity of recombinant carboxypeptidase B utilizing
      CE-SDS has been developed and validated for use in a manufacturing quality
      control laboratory. The method was optimized, prior to validation, to allow for
      the lowest limit of quantitation. The method was validated with the typical
      ICHQ2A parameters, including accuracy, linearity, LOQ, precision,
      robustness/ruggedness, and specificity. All validation parameters met the
      acceptance criteria defined in the validation protocol.

PMID- 15163856
TI  - Analysis of neutral N-linked oligosaccharides from antibodies using free-solution
      capillary electrophoresis in bare fused-silica capillaries.
AB  - Conditions for the enzymatic release, chemical derivatization, and analysis of
      oligosaccharides from the consensus glycosylation sites on antibodies are
      described. Release of the oligosaccharides is from the native protein. The APTS
      derivatives of the released oligosaccharides are then analyzed by capillary
      electrophoresis (CE) using a free solution separation in a bare fused silica
      capillary. An example of the application of the method to the analysis of the
      oligosaccharide population from antibodies obtained from different cell lines is
      provided. The separation conditions provide for resolution of various galactose
      positional isomers, including those derived from different linkage
      configurations.

PMID- 15163857
TI  - Affinity capillary electrophoresis to examine receptor-ligand interactions.
AB  - Afffinity capillary electrophoresis (ACE) is a new analytical technique that has
      been shown to be an efficient and accurate tool in studying biomolecular
      noncovalent interactions and determining binding and dissociation constants of
      formed complexes. ACE uses as its basis the change in migration time of a
      receptor upon binding to a ligand found in the electrophoresis buffer. Subsequent
      Scatchard analysis using noninteracting markers realizes a binding constant.
      Herein, ACE and three modifications in the technique, partial-filling ACE
      (PFACE), flow through PFACE (FTPFACE), and multiple-step ligand injection ACE
      (MSLIACE) are used to probe the binding of ristocetin A (Rist A) and vancomycin
      (Van) from Streptomyces orientalis to D-Ala-D-Ala terminus peptides and carbonic
      anhydrase B (CAB, E.C.4.2.1.1) to arylsulfonamides.

PMID- 15163858
TI  - Screening major binding sites on human serum albumin by affinity capillary
      electrophoresis.
AB  - A screening method is described for determining whether a drug or small solute
      has significant interactions at the two major binding sites on human serum
      albumin (HSA). This method uses affinity capillary electrophoresis (ACE) to
      perform a mobility shift assay, where the solute of interest is injected in both
      the presence of pH 7.4, 0.067 M phosphate buffer, and the same buffer containing
      a known concentration of HSA. Dextran is also used in the running buffer to
      adjust the mobility of HSA. Two types of modified HSA are used in this assay. The
      first is modified with 2-hydroxy-5-nitrobenzyl bromide (HNB), which selectively
      blocks HSA's warfarin-azapropazone site. The second type of HSA is modified with
      tetranitromethane (TNM), which decreases binding at the indole-benzodiazepine
      site. By comparing the mobility of a solute in the presence of these two modified
      forms of HSA vs normal HSA, it is possible to detect solute interactions at these
      binding sites. This approach is illustrated using warfarin and ibuprofen as
      examples of test solutes.

PMID- 15163859
TI  - Using charge ladders and capillary electrophoresis to measure the charge, size,
      and electrostatic interactions of proteins.
AB  - This chapter provides an overview of protein charge ladders--collections of
      protein derivatives that differ in charge--and capillary electrophoresis (CE).
      The combination of charge ladders and CE is a useful biophysical tool for
      measuring the net charge of proteins and the role of electrostatics in
      biochemical processes involving proteins. Methods to synthesize and analyze
      charge ladders by CE are described. Applications of charge ladders and CE to the
      simultaneous measurement of net charge and hydrodynamic radius of proteins are
      presented. Techniques for using charge ladders and CE to measure the role of
      interactions between charged groups on protein stability and ligand binding are
      also given. The power of this approach lies in the ability to isolate protein
      charge as an independent and measurable variable in the study of protein
      stability and function.

PMID- 15163860
TI  - Frontal analysis continuous capillary electrophoresis for protein-polyelectrolyte
      binding studies.
AB  - A novel technique, frontal analysis continuous capillary electrophoresis (FACCE),
      has been described as an effective way to study protein-polyelectrolyte binding.
      FACCE involves continuous sampling, integrating sample injection and separation
      into one process that provides advantages over conventional frontal
      chromatography. The method provides rapid and precise determination of binding
      isotherms, and allows for quantitative binding analysis in terms of binding
      constant and the binding-site size by considering the protein as the ligand and
      allowing the polyelectrolyte to bind to a number of proteins with variable levels
      of cooperativity. FACCE is particularly suitable for binding systems involving
      rapid binding kinetics because it allows for the determination of the
      concentrations of free or bound ligands under conditions that avoid perturbation
      of the binding equilibrium. This chapter focuses on studies of the binding of
      bovine serum albumin (BSA) to heparin using FACCE. These investigations are
      demonstrated within the context of this chapter as representative of a model
      protein-polyelectrolyte system from which extensions to other systems can be
      made.

PMID- 15163861
TI  - Analysis of proteins by CE, CIEF, and microfluidic devices with whole-column
      imaging detection.
AB  - The recently developed whole-column-imaging detection technique for capillary
      electrophoresis (CE) and capillary isoelectric focusing (CIEF), a commercial
      whole-column-imaged CIEF instrument and its standard operation protocol are
      introduced. Furthermore, new developments and applications of whole-column
      imaging detection in protein-protein interaction study, in protein separation
      using microfluidic devices and CIEF methods without carrier ampholytes, as well
      as in 2D separation techniques are reviewed. Miniaturization of whole-column
      imaging CIEF and axially illuminated fluorescence whole-column-imaging CIEF are
      also discussed.

PMID- 15163862
TI  - Capillary electrophoresis-electrospray ionization mass spectrometry of amino
      acids, peptides, and proteins.
AB  - Separation in capillary electrophoresis (CE) is based on the movement of charged
      compounds inside a background electrolyte under an applied potential. Because the
      mechanism of separation of CE differs from that of conventional high-performance
      liquid chromatography (HPLC), where separation is based on the analyte's
      hydrophobic properties, CE is often used as a complementary technique to HPLC. In
      addition, because CE is performed in narrow capillaries at atmospheric pressure,
      it is used as an alternative to HPLC, capable of handling small sample volumes
      while providing shorter analysis times with higher efficiency. For the analysis
      of amino acid, protein, and peptide mixtures in small volume samples such as in
      single cells, CE has rapidly evolved as a preferred separation technique. The
      combination of a high-efficiency separation technique, such as CE, with mass
      spectrometry (MS) detection provides a powerful system for the analysis of
      complex biological mixtures. In this chapter, a theoretical and practical
      approach to achieving high-performance CE-MS is discussed and the utility of CE
      MS for the analysis of amino acids, peptides, and proteins is demonstrated.

PMID- 15163863
TI  - Capillary isoelectric focusing--mass spectrometry of proteins and protein
      complexes.
AB  - Complex proteome samples require efficient separation and detection methods in
      order to characterize their protein components. On-line combination of capillary
      isoelectric focusing (CIEF) with electrospray ionization (ESI) mass spectrometry
      (MS) is shown as an effective method to analyze complex protein mixtures. Our
      experience with several microorganisms allowed us to establish successful
      experimental protocol. Here we use the example of E. coli whole-cell lysate for
      the CIEF separation and MS detection on the intact protein level. The protocol
      was further adapted for the analysis of the mixture of noncovalent complexes on
      the intact complex level.

PMID- 15163864
TI  - Integrated system for rapid proteomics analyses using microfluidic devices
      coupled to nanoelectrospray mass spectrometry.
AB  - This chapter presents an integrated and modular microsystem providing rapid
      analyses of low femtomole of in-gel digests for proteomics applications.
      Enhancement of sample throughput is facilitated using an autosampler, a
      microfabricated device comprising a large (2.4-microL total volume) separation
      channel together with a low-dead-volume interface to nES mass spectrometry.
      Sample preconcentration is achieved by packing C18 reverse phase or immobilized
      metal affinity chromatography (IMAC) beads into the large channel of this
      microfluidic device to adsorb peptides or enrich the sample in phosphopeptides
      prior to capillary electrophoresis separation and MS detection. This integrated
      microfluidic systems enables a sample throughput of up to 12 samples/h with a
      detection limit of approx 5 nM (25 fmol inj.). Replicate injections of peptide
      standards indicated that reproducibility of migration time was typically 1.2
      1.8%, whereas relative standard deviation (RSD) values of 9.2-11.8% were obtained
      on peak heights. The application of this device is demonstrated for 2D gel spots
      obtained from protein extracts of human astrocyte cells and for excised bands of
      membrane proteins from Neisseria meningitidis. A stepped acetonitrile gradient
      can be incorporated with the present microfluidic system to enhance selectivity
      during sample analysis.

PMID- 15163865
TI  - The Indian picture puzzle test - a developmental test designed and standardised
      for Indian children.
AB  - OBJECTIVE: To construct a test used by community pediatricians and other
      professionals in the UK as a screening test for verbal and non-verbal development
      in children aged 2 to 4 years of age. METHODS: A multifaceted developmental test
      of cognitive skills was constructed, modeled on the Bus Puzde Test (Egan 1984)
      for its case of administration and appeal. Each stage in the design was piloted
      in Rajasthan in all socioeconomic groups. Stages include simple ethnic
      modification of the original test, development of more socioculturally
      appropriate scenes, a detailed statistical procedure of item analysis and
      reliability studies. The picture was converted into a wooden insert puzzle,
      called The Indan Picture Puzzle Test (IPPT) and standardized on a random sample
      of 616 children to construct the norms. RESULT: The IPPT assesses aspects of
      early language, picture interpretation, performance skills and conceptual
      development in children aged 2 to 5 years. Analysis of the standardized data
      highlighted the need for separate norms for each socioeconomic group. CONCLUSION:
      Verbal abilities were significantly different between advantaged and
      disadvantaged (slum and rural) groups though performance skills were comparable.

PMID- 15163866
TI  - Surgical implications of snakebites.
AB  - OBJECTIVE: Snakebites are a common problem in the pediatric age group. Local
      complications such as necrosis and compartment syndrome threaten limb survival
      even after control of systemic manifestations. Few recommendations exist about
      the nature and timing of surgical treatment. METHODS: A retrospective review of
      all children with snakebites presenting to the hospital was undertaken over a 6
      year period. Records were reviewed with special emphasis on the type of surgical
      lesions seen and the treatment offered and their results. RESULTS: 44 of the 58
      children required some form of local therapy. In the majority conservative
      treatment was successful. 28% of the patients needed debridement for local
      necrosis, and only 5 needed a skin graft, with good functional results over a
      period of 1 to 45 days. One child underwent an above knee amputation. Patients
      who required surgical intervention received significantly more vials of
      antivenin. CONCLUSION: Local complications of snakebite are frequent, but can be
      managed conservatively. Delayed excision of the resultant local necrosis is
      associated with good outcomes. The need for fasciotomy is rare.

PMID- 15163867
TI  - Health status of siblings of hospitalized children.
AB  - OBJECTIVE: To study health status of siblings of children hospitalized for
      various diseases. METHODS: A total of 308 siblings of 200 hospitalized children
      were studied by detailed history, anthropometry, physical examination and
      relevant laboratory tests. RESULTS: Only 43.83% siblings were fully immunized,
      25.32% partially and 30.85% were totally unimmunized. Normal nutritional status
      was seen in 20.43% siblings; 26.95% had grade 1, 25.64% grade II, 24.02% grade
      III and 2.92% had grade IV malnutrition. Various morbid conditions were observed
      in siblings, the common ones were vit. A deficiency (22.40%), worm infestation
      (21.42%), anemia (19.15%), dental caries (13.63%), ARI (13.31%), diarrhoea
      (12.01%), malaria (7.46%) and scabies (7.14%). CONCLUSION: The siblings of
      hospitalized children are in a high-risk group as they share same environment and
      nutrition. They have various ailments in various stages of severity. The health
      screening of such children will have a positive impact in promoting health and
      diagnosing diseases at an early stage.

PMID- 15163868
TI  - Mental health status of runaway adolescents.
AB  - There are 47.22 million homeless and runaway adolescents roaming on the streets
      of our country (Voluntary Health Association of India - VHAI) of which one lakh
      are in Delhi.1 Very little is known about them, their needs or their experiences.
      OBJECTIVE: (1). To assess the psychological problems amongst the runaway
      adolescent boys. (2). To determine possible risk factors. METHODS: This study was
      cross-sectional in design and done at a child observation home for boys in Delhi.
      All runaway boys aged 10 to 16 years of age were included in the study. The study
      was conducted from 15th June to 15th July 2001. A comprehensive schedule
      consisting of five parts, viz identification data, hopelessness scale for
      children by Kazdin, Beck depression inventory, Psychological survey questionnaire
      and RUTTER-B2 scale were used to assess various mental health problems. RESULTS:
      20.7% of children were found to have high hopelessness and 8% of children had
      depression. 2% of children revealed that they had attempted suicide at any point
      of time in life. Among children with high hopelessness, 3.2% had ever attempted
      suicide. 8.3% of the depressed children gave history of suicidal attempts. 38% of
      children gave history of physical abuse, 14.6% of sexual abuse and a large number
      reported substance abuse. 69.33% were found to have behavioral problems (i.e.
      scored above the recommended cut off score of 9). 81% of children had antisocial
      behavior, 7.8% were neurotic and 10.5% remained undifferentiated. CONCLUSION:
      Runaway adolescents suffer from a wide array of mental health problems and there
      is a need for a broad based psychosocial intervention programme.

PMID- 15163869
TI  - Cefpodoxime - utility in respiratory tract infections and typhoid fever.
AB  - Cefpodoxime is a oral third generation cephalosporin active against most of gram
      positive and gram negative bacteria except Pseudomonas, B. fragilis and
      Entrococcous. Clinical studies have confirmed efficacy of cefpodoxime in acute
      otitis media, sinusitis and tosillopharyngitis. Twice daily administration and
      safety profile increases compliance and decreases failure rate. It has a role as
      switch over therapy from intravenous ceftriaxone in serious respiratory tract
      infections (RTIs). In areas where common respiratory pathogens show decreased
      sensitivity to penicillins and macrolides cefpodoxime can be used as empirical
      first line therapy in respiratory tract infections. It seems to be a promising
      molecule in pediatric typhoid fever because of its excellent activity against
      Salmonella species but clinical trials are limited.

PMID- 15163870
TI  - Breast feeding and childhood hematological malignancy.
AB  - Breast milk is known to have anti-infective and immunomodulating effects on
      infants, but its association with childhood cancer has not been well studied.
      Artificial feeding may affect the immune response in carcinogenesis. In this
      communication the authors have reviewed different articles describing the
      association between breast feeding (BF) and subsequent development of childhood
      hematological malignancy. It appears that BF may have a protective effect on
      childhood cancer, both the duration of BF as well as the quantity of milk
      ingested is probably critical to the beneficial immunological effects of BF
      against childhood cancer if any.

PMID- 15163871
TI  - Umbilical cord allantoic cysts in a newborn with vacterl association.
AB  - Allantoic cysts of umbilical cord are very rare. A preterm, low birth weight,
      male newborn with a new constellation of anomalies, allantoic duct cysts in the
      umbilical cord and associated perinatally lethal malformations of VACTERL
      sequence, is reported. In addition, the neonate also had duodenal atresia, patent
      urachus, obstructive uropathy and bifid scrotum. Association of Allantoic cysts
      with VACTERL sequence has not been described earlier.

PMID- 15163872
TI  - Streptococcus pyogenes meningitis.
AB  - Group A Streptococcus (GAS) is a rare cause of meningitis. Although it has a high
      mortality, the condition is easily treatable if diagnosed early since the
      bacteria retains its sensitivity to many antimicrobials. The authors report here
      two cases of GAS meningitis along with a review of world literature.

PMID- 15163873
TI  - Nitric oxide in preterm infant with pulmonary hypoplasia.
AB  - Premature infants with hypoplastic lungs may have elevated pulmonary vascular
      resistance with right to left shunt across ductus arteriosus and/or foramen
      ovale. Inhaled nitric oxide (NO) being selective pulmonary vasodilator without
      significant effects on systemic circulation can potentially reverse this shunt.
      The authors herewith report a case of a premature infant with severe hypoxemic
      respiratory failure after preterm premature prolonged rupture of membranes
      leading to oligohydramnios and pulmonary hypoplasia that was treated successfully
      with NO and describe the neurodevelopmental outcome at 1 year of age.

PMID- 15163874
TI  - Non hodgkin's lymphoma seven years following remission of acute lymphoblastic
      leukemia.
AB  - The authors describe a case of extramedullary relapse in lymph node presenting as
      lymphoblastic lymphoma seven years following remission of acute lymphoblastic
      leukemia. To the best of our knowledge, this is the first reported case of an
      isolated lymph node relapse with hematopoietic remission of leukemia. We have
      discussed cases of large cell lymphoma and other unusual areas of extramedullary
      relapse complicating acute lymphoblastic leukemia in hematopoietic remission.

PMID- 15163875
TI  - Toxic shock syndrome.
AB  - The authors present two children who had fever >or=38.9 degree C, diffuse rash,
      hypotension, deranged renal and hepatic functions, disseminated intravascular
      coagulation, altered sensorium and inflamed oral mucosa. They responded to
      fluids, inotropes, antibiotics and intravenous immunoglobulin (2 g/kg).
      Desquamation particularly of palms and soles and periungal region was noted 1 to
      2 weeks after onset of illness. These features were consistent with the diagnosis
      of staphylococcal toxic shock syndrome (TSS). The cases highlight that TSS is
      very much with us and can mimic a variety of other diseases. Early recognition,
      and aggressive antimicrobial supportive and IVIG therapy cover can ensure
      complete recovery.

PMID- 15163876
TI  - Sengers disease: a rare association of hypertrophic cardiomyopathy and congenital
      cataracts.
AB  - Hypertrophic cardiomyopathy is an uncommon childhood cardiac disease and can be
      primary or secondary. Several systemic diseases are known to be associated with
      this entity. Senger's disease is a mitochondrial disorder causing congenital
      cataracts lactic acidosis and skeletal and cardiac myopathy. Diagnosis should be
      kept in mind when routine neonatal eye screening reveals absent red reflex. The
      authors report a case of Sengers disease and discuss the underlying pathogenetic
      mechanisms.

PMID- 15163877
TI  - Congenital factor VII deficiency.
AB  - A 1(1/2)-month-old baby with seizures, lethargy and refusal of feeds was
      diagnosed to have intracranial hemorrhage due to factor VII deficiency. MRI also
      demonstrated the unusual presence of a hemorrhagic infarct. The case underscores
      the importance of carrying out neuroimaging and appropriate hematological studies
      even in the absence of obvious external bleeding. Hypothesis for increased
      propensity for intra-cranial hemorrhage is discussed.

PMID- 15163878
TI  - Hirschsprung's disease complicating colonic atresia.
AB  - A case of colonic atresia associated with Hirschsprung's disease is described in
      a full term neonate presented with intestinal obstruction. Laparotomy revealed
      type III colonic atresia. Histopathological examination suggested total
      aganglionosis in the postatretic colonic segment. The child recovered
      satisfactorily following two stage Duhamel - Martin's pull through procedure.
      Authors present their experience with the present case and the pertinent
      literature.

PMID- 15163879
TI  - Sirenomelia with radial dysplasia.
AB  - Sirenomelia is a rare anomaly usually associated with other multiple
      malformations. In this communication the authors report a case of sirenomelia
      associated with multiple malformations, which include radial hypoplasia also.
      Though several theories have been proposed regarding the etiology of multiple
      malformation syndromes in the past, the recent theory of primary developmental
      defect during blastogenesis holds good in this case.

PMID- 15163880
TI  - Heterotopic neuroglial tissue in hard palate.
AB  - Heterotopic neuroglial condition is a rare congenital anomaly in children. Most
      of the reported cases have been located in nose. To date, there was no recorded
      case of heterotopic neuroglial tissue in hard palate without any other congenital
      anomaly. The purpose of this report is to present a rare case of heterotopic
      neuroglial tissue in hard palate to add to literature we reviewed.

PMID- 15163881
TI  - Pyknodysostosis: visceral manifestations and simian crease.
AB  - Pyknodysostosis is a rare autosomal recessive osteosclerosing skeletal disorder
      caused by mutations in the CTSK gene situated at 1q21 that codes for cathepsin K 
      a lysosomal cysteine protease. Mutations in this gene affect the metabolism of
      skeletal system. This causes problems in bone resorption and remodelling and
      craniofacial abnormalities. In this article we report a case of 12 year old
      female from Punjab with pyknodysostosis having hepatosplenomegaly and simian
      crease.

PMID- 15163882
TI  - Esophageal tuberculosis.
AB  - Esophageal tuberculosis is a rare clinical entity even in adults. Esophageal
      tuberculosis, can be either primary or secondary, the former is less common as
      compared to the latter. The authors present a 14-year-old boy, who presented with
      vomiting, cough, low-grade fever and anorexia for two months. He had a positive
      mantoux with history of contact to Tuberculosis. Upper GI scopy revealed an
      irregular ulcer in the mid esophagus and the biopsy was suggestive of
      tuberculosis. The CT scan of the chest showed consolidation left lower lobe with
      hilar and mediastinal adenopathy. He responded well to ATT.

PMID- 15163883
TI  - Spectrum of clinical presentations of vein of galen aneurysm.
AB  - Aneurysm of the vein of Galen is a rare intracranial vascular malformation. It is
      known to have diverse manifestations and varying severity. Four cases with
      different modes of presentation and outcome are reported. A mortality of 50 per
      cent was encountered. Among the survivors, one had neurologic sequelae whereas
      the other had attained age-appropriate developmental milestones. The former was a
      rare case of spontaneous thrombosis of the aneurysm while the latter was a boy
      who underwent therapeutic embolization.

PMID- 15163884
TI  - Wilm's tumor in a solitary kidney complicated by chemotherapy induced obstructive
      uropathy.
AB  - A three-year-old male child with Wilm's tumor of left kidney and right sided
      unilateral renal agenesis is reported. The left renal vein was located posterior
      to the aorta. He was managed with medical measures alone. The initial phase of
      treatment was complicated by chemotherapy induced dislodgment of the tumor
      fragment and subsequent distal obstruction.

PMID- 15163886
TI  - Megalencephalic leukoencephalopathy with subcortical cysts.
AB  - Megalencephalic leukocncephalopathy is rare disorder seen in India in patient
      belonging to Agarwal community. Many of the patients may have a mild clinical
      course with gradual worsening of neurological disability. A case is being
      reported who was followed for 17 years and paradoxically showed radiological and
      clinical improvement.

PMID- 15163885
TI  - Isolated "one and a half syndrome" with brainstem tuberculoma.
AB  - A seldom reported causal association of two rare entities, an isolated brainstem
      tuberculoma and an isolated One and a half syndrome in a 12 year old girl is
      presented. MRI showed an isolated inflammatory granuloma in the brainstem which
      on empirical treatment with anti tubercular drugs resulted in complete
      restoration of ocular motility, along with resolution of the lesion on follow up
      MRI at 6 months. The diagnosis and management are discussed.

PMID- 15163887
TI  - Congenital prepubic sinus.

PMID- 15163889
TI  - T cells recognize multiple GAD65 and proinsulin epitopes in human type 1
      diabetes, suggesting determinant spreading.
AB  - Human type 1 diabetes is thought to be mediated by autoreactive T cells specific
      for antigens expressed by pancreatic beta cells. However, it is unclear which
      autoantigens and determinants thereof are the targets of the autoimmune attack.
      Using comprehensive peptide libraries that cover the entire sequence of two major
      candidate autoantigens, GAD65 and proinsulin, we measured the in vivo frequencies
      of peptide-specific, IFN-gamma-producing memory T cells in 27 diabetic patients,
      14 high risk individuals, and 15 partially HLA-matched healthy controls. Compared
      to the controls, both a higher number of determinants on the islet cell antigens
      were recognized and the frequencies of peptide specific cells were increased in
      patients and high risk individuals. Inclusion of signal enhancing anti-CD28
      antibody further accentuated this difference. Considerable heterogeneity in
      peptide recognition was seen even in DRB1*04, DQB1*0302 matched individuals.
      Unlike its peptides, the GAD protein antigen did not recall a T cell memory
      response. The highly heterogeneous recognition of a multitude of peptide
      determinants on both autoantigens, occurring in the absence of protein
      recognition, and the low functional avidity of the memory cells involved jointly
      suggest that the autoimmune T cell repertoire in human type 1 diabetes primarily
      targets cryptic determinants engaged by determinant spreading.

PMID- 15163888
TI  - Inhibitory Fc gamma receptors: from gene to disease.
AB  - Multiple lines of evidence have revealed a key role for inhibitory Fc gamma
      receptors class IIb (FcgammaRIIb) as negative modulators of innate and adaptive
      immune responses. Acquired and genetic factors regulate the expression of
      FcgammaRIIb receptors and modify their inhibitory potential. Recent advances have
      highlighted the importance of FcgammaRIIb receptors in influencing the
      development of cancer and autoimmunity. The association of increased FcgammaRIIb
      expression with tumor development is believed to operate at effector cell level
      resulting in inhibition of antitumor cytotoxicity. In autoimmune diseases,
      FcgammaRIIb receptors play a major role in controlling the amplitude of antibody-
      and immune complex-mediated reactions. Generally, FcgammaRIIb deficiency is
      associated with increased susceptibility and severity to organ-specific and
      systemic autoimmunity. This article discusses the proposed mechanisms for
      FcgammaRIIb deregulation associated with malignant and autoimmune pathology in
      animal models and human diseases.

PMID- 15163890
TI  - Analysis of somatic hypermutation and antigenic selection in the clonal B cell in
      immunoglobulin light chain amyloidosis (AL).
AB  - Light chain amyloidosis (AL) is a protein folding disorder with an underlying B
      cell neoplasia where the monoclonal immunoglobulin light chains (LCs) produced
      from insoluble amyloid fibrils. The deposition of these fibrillar aggregates in
      vital organs causes severe organ dysfunction over time and is associated with
      high mortality. We have identified the postgerminal center status of the B cell
      clone by evaluating the presence of somatic hypermutation in the variable region
      of the LC gene in 27 (13 of the lambda and 14 of the kappa subtype) AL patients.
      Seven of the 27 clones showed statistically significant evidence of antigenic
      selection, using a multinomial algorithm. The framework region mutations were
      selected for conservation of protein structure in 13 of the 27 patients.
      Additionally, mutational clusterspots were identified at specific positions in
      the nucleotide and deduced protein sequence that could potentially contribute to
      destabilizing interactions resulting in a propensity to form amyloid.

PMID- 15163891
TI  - Antibody levels after regular childhood vaccinations in the immunological
      screening of children with recurrent otitis media.
AB  - Recurrent otitis media may be related to defects in specific antibody production,
      as suggested previously. This might be reflected in lower antibody responses to
      vaccinations administered in the context of the national childhood vaccination
      program in children suffering from recurrent otitis media. In a cross-sectional
      study we determined the levels of antidiphtheria, antitetanus, anti- Haemophilus
      influenzae type b (anti-Hib) and antimeasles antibodies in sera of 163 children
      with two or more episodes of acute otitis media per year and in 143 children with
      repeated periods of persistent otitis media with effusion each lasting at least 3
      months. The control group consisted of 521 age-matched healthy children, who were
      free of recurrent respiratory tract infections. Children with recurrent acute
      otitis media, including highly otitis-prone children, showed higher
      antidiphtheria and antitetanus antibody titers compared to controls. No
      differences were observed in anti-Hib and antimeasles antibody levels between
      children with recurrent acute otitis media and controls, nor did any of the
      antibody levels in children with persistent otitis media with effusion differ
      from those in controls. Therefore, the results of our study do not point toward a
      generalized immunological hyporesponsiveness in children with recurrent acute
      otitis media and persistent otitis media with effusion. Determination of antibody
      responses to regular vaccines is not indicative for otitis-proneness.

PMID- 15163892
TI  - Systemic treatment with either cyclosporin A or methotrexate does not influence
      the T helper 1/T helper 2 balance in psoriatic patients.
AB  - Cyclosporin A and methotrexate are highly effective drugs in the treatment of
      psoriasis. It was hypothesized that these therapies might modulate T helper cell
      cytokine secretion patterns or T cell migration patterns. Flow cytometric
      determination of interferon-gamma (IFNgamma) and interleukin 4 (IL4) producing T
      helper cell frequencies, as well as of cutaneous lymphocyte associated antigen
      (CLA) expressing T cell frequencies was performed in patients suffering from
      severe psoriasis, before, during, and after a scheduled immunosuppressive regimen
      with either cyclosporin A or methotrexate. Both cyclosporin A and methotrexate
      treatment reduced the psoriasis area severity index score after 12 weeks of
      treatment. Cyclosporin A treatment reduced the frequencies of IL4-producing
      CD4(pos) T cells, without significantly affecting the T helper 1 to T helper 2
      (Th1/Th2) balance but in conjunction with the decreasing number of peripheral
      blood eosinophil counts. In methotrexate-treated patients, the Th1/Th2 balance
      was unaffected. Cessation of both therapies resulted in increased numbers of
      IFNgamma- as well as IL4-producing CD4(pos) T cells as compared to before
      initiation of oral therapy. Methotrexate, but not cyclosporin A, treatment
      reduced the frequencies of circulating skin-homing CLA(pos) T cells. This effect
      was reversed by 4 weeks after withdrawal of methotrexate therapy. We conclude
      that (1) neither cyclosporin A nor methotrexate affects the balance between Th1
      and Th2 cells; (2) exaggerated cytokine production by T helper cells after
      cessation of oral cyclosporin A or methotrexate drug treatment may contribute to
      the reappearance of psoriatic skin lesions; and (3) decrease of circulating skin
      homing T cells may be responsible for part of the therapeutic effect of
      methotrexate in severe psoriasis.

PMID- 15163893
TI  - Interleukin-4 cellular gene therapy and osteoprotegerin decrease inflammation
      associated bone resorption in collagen-induced arthritis.
AB  - To evaluate the respective action of IL-4, an anti-inflammatory cytokine, and
      OPG, an inhibitor of bone resorption, on the inflammatory process and the
      associated bone resorption in collagen-induced arthritis (CIA). After CIA
      induction, DBA/1 mice were treated with OPG or with IL-4 DBA/1 transfected
      fibroblasts or both OPG + IL-4. CIA significantly improved in IL-4 groups. OPG
      had no effect on arthritis clinical scores but histologic scores were reduced in
      OPG, IL-4, and OPG + IL-4 groups vs. nontreated CIA mice. OPG increased
      significantly BMD and decreased by 45% D-pyridinolin levels. Moreover association
      of IL-4 and OPG exerted an additive effect of BMD and resorption marker (-68%).
      Production of IFN-gamma in the supernatants of spleen cells was reduced in IL-4
      treated mice. OPG had a moderate effect on IFN-gamma, but potentiated the
      inhibitory effect of IL-4. OPG and IL-4 prevent bone loss in CIA-mice model and
      could have additive effects on IFN-gamma secretion.

PMID- 15163894
TI  - Immunity in HIV-1-infected adults with a previous state of moderate-severe immune
      suppression and more than 500 CD4+ T cell after highly active antiretroviral
      therapy.
AB  - We evaluated phenotypic and functional parameters of immune restoration of 27 HIV
      infected patients on highly active antiretroviral therapy (HAART) (HIV-cases)
      with HIV-RNA levels below detectable limits at least during 18 months, and CD4+
      cell per microliter higher than 500 at the moment of the study and lower than 300
      anytime before. These patients were compared with 11 HIV-controls that never had
      less than 500 CD4+ cell per microliter and 20 healthy-controls (HIV seronegative
      subjects) in a cross-sectional study. HIV-cases had lower counts of naive CD4+
      than HIV-controls and healthy-controls. HIV-patients (both HIV-cases and HIV
      controls) showed higher values of naive and memory CD8+ counts than healthy
      controls. TREC-bearing cell levels were significantly lower in HIV-cases than in
      healthy-controls. Peripheral blood mononuclear cells (PBMC) cultures, HIV-cases
      had lower values in proliferation to streptokinase (SK) and tetanus toxin (TT)
      than in healthy-controls. HIV-cases had lower IFN-gamma and higher IL-5
      production with pokeweed than healthy-controls ( P < 0.01). However, IL-5
      production of HIV-cases after TT stimulation was lower than in HIV-controls and
      healthy-controls. Total IgG and IgG1 levels were significantly higher in HIV
      cases than in HIV-controls and healthy-controls. Also, IgM levels were
      significantly higher in HIV-cases than in healthy-controls. Nevertheless, IgG2
      levels were significantly lower in HIV-cases and HIV-controls than in healthy
      controls. The levels of specific Igs antipneumococcal capsular polysaccharide and
      TT were significantly lower in HIV-cases than in healthy-controls. HIV-patients
      with a previous state of severe-moderate immunosuppression normalizing their CD4+
      counts have a incomplete immune reconstitution after HAART. Long-term
      consequences of this subclinical immune deficiency remain to be determined.

PMID- 15163895
TI  - Safety, efficacy, and pharmacokinetics of Flebogamma 5% [immune globulin
      intravenous (human)] for replacement therapy in primary immunodeficiency
      diseases.
AB  - The purpose of the study was to evaluate the safety, efficacy, and
      pharmacokinetics of Flebogamma 5%, an immune globulin intravenous product, for
      replacement therapy in primary immunodeficient patients. The US Food and Drug
      Administration has proposed that the use of new products must result in < or =1
      serious bacterial infection/subject/year, have acceptable safety and
      tolerability, and have pharmacokinetic properties similar to endogenous IgG and
      other commercially available immune globulin products. Flebogamma 5% was
      administered at seven clinical sites to 51 subjects aged 14-74 years with well
      defined primary immunodeficiency diseases at a dose of 300-600 mg/kg every 21-28
      days for 12 months. The calculated serious infection rate for the intent-to-treat
      population was 0.061/subject/year. The incidence of adverse events considered
      potentially related to Flebogamma 5%, and occurring during or within 72 h after
      completing the infusion was approximately 8%. The half-life of total IgG was 37
      days. Flebogamma 5% is efficacious, safe, and well-tolerated, and does not put
      subjects at increased risk of adverse events other than those that could be
      reasonably expected in primary immunodeficient subjects who are receiving any
      immune globulin product.

PMID- 15163897
TI  - Antibody response to a seven-valent pneumococcal conjugated vaccine in patients
      with ataxia-telangiectasia.
AB  - Immunodeficiency is a characteristic feature of ataxia-telangiectasia (A-T).
      Humoral immunodeficiency generally consists of hypogammaglobulinemia and impaired
      antibody response to bacterial and viral antigens. We previously observed
      defective antibody response to 23-valent pneumococcal polysaccharide vaccine
      (PPV) in 96% of 29 patients with A-T. In this study, we investigated the antibody
      response to a seven-valent pneumococcal conjugate vaccine, PCV7, in 14 patients
      with A-T. IgG antibody levels to four pneumococcal serotypes, 6B, 14, 19F, 23F,
      which were included in PCV7, were measured by ELISA in pre- and postimmunization
      serum samples. Antibody titers against each individual Streptococcus pneumoniae
      serotype was considered to be positive when serotype specific pneumococcal
      antibody titer was higher than 10% (>10 U/mL) of the reference plasma pool level.
      However, when the fold increase (FI) in postimmunization antibody titer was less
      than two, the subject was determined to be unresponsive to the given serotype.
      The values were compared with the results obtained in age- and ethnic-matched
      children after one dose of PPV. Only two patients produced antibodies to one
      serotype each; one to serotype 19 with a fold increase of <2, and the other to
      serotype 23F with a fold increase of 5.7 based on the above criteria, although
      the differences between pre- and postvaccine antibody titers for serotypes 14,
      19, and 23 appeared to be statistically significant. In conclusion, A-T patients
      failed to respond to one dose of PCV7 vaccine. Two or more doses of conjugated
      vaccine may be required to recruit the help of T lymphocytes in A-T patients.

PMID- 15163896
TI  - Griscelli syndrome: characterization of a new mutation and rescue of T-cytotoxic
      activity by retroviral transfer of RAB27A gene.
AB  - Griscelli syndrome (GS) is caused by mutations in the MYO5A (GS1), RAB27A (GS2),
      or MLPH (GS3) genes, all of which lead to a similar pigmentary dilution. In
      addition, GS1 patients show primary neurological impairment, whereas GS2 patients
      present immunodeficiency and periods of lymphocyte proliferation and activation,
      leading to their infiltration in many organs, such as the nervous system, causing
      secondary neurological damage. We report the diagnosis of GS2 in a 4-year-old
      child with haemophagocytic syndrome, immunodeficiency, and secondary neurological
      disorders. Typical melanosome accumulation was found in skin melanocytes and
      pigment clumps were observed in hair shafts. Two heterozygous mutant alleles of
      the RAB27A gene were found, a C-T transition (C352T) that leads to Q118stop and a
      G-C transversion on the exon 5 splicing donor site (G467+1C). Functional assays
      showed increased cellular activation and decreased cytotoxic activity of NK and
      CD8+ T cells, associated with defective lytic granules release. Myosin-Va
      expression and localization in the patient lymphocytes were also analyzed. Most
      importantly, we show that cytotoxic activity of the patient's CD8+ T lymphocytes
      can be rescued in vitro by RAB27A gene transfer mediated by a recombinant
      retroviral vector, a first step towards a potential treatment of the acute phase
      of GS2 by RAB27A transduced lymphocytes.

PMID- 15163898
TI  - Effect of montelukast, a cysteinyl receptor antagonist, on myofibroblasts in
      interstitial lung disease.
AB  - Montelukast, a potent cysteinyl receptor antagonist, may be an antifibrotic
      therapeutic agent for lung fibrosis. Seven sarcoidosis patients and 10 with
      unusual interstitial pneumonia underwent conventional bronchoalveolar lavage,
      from which myofibroblasts were recovered. Myofibroblast proliferation was
      assayed, alpha smooth muscle actin levels were measured, TGFbeta mRNA RT-PCR
      transcripts were semiquantitated, and secretion was evaluated in myofibroblast
      supernatants. Montelukast at 10(-8) M concentration had a suppressive effect on
      cell proliferation (31 +/- 18%), which was significantly enhanced by LTD4 10(-8)
      M. No differences were found between sarcoidosis (31.28 +/- 15.9%) and unusual
      interstitial pneumonia (30.56 +/- 24.3%) lines. Fetal calf serum (20%) produced
      an enhancing effect (29.8 +/- 21.6%) in all lines. Myofibroblasts recovered from
      sarcoidosis patients showed lower alpha-smooth muscle actin contents than unusual
      interstitial pneumonia lines (0.09 +/- 0.02 vs. 0.34 +/- 0.16, p =0.039,
      respectively). Montelukast suppressed alpha-actin in short-term cultures in
      sarcoidosis myofibroblasts and in long-term unusual interstitial pneumonia
      myofibroblasts. Montelukast at 10(-6) M concentratin decreased the TGFbeta
      induced alpha-actin expression in all lines tested. Montelukast decreased mRNA
      expression of TGFbeta. Montelukast may be a therapeutic agent in pathological
      conditions involving fibrotic and remodeling processes.

PMID- 15163899
TI  - Th2 cytokines IL-4 and IL-13 downregulate paxillin expression in bronchial airway
      epithelial cells.
AB  - Asthma is characterized by infiltration and shedding of the bronchial epithelium.
      The Th2 cytokines IL-4 and IL-13 are involved in the cellular recruitment and
      infiltration seen in asthma. The effects of IL-4 and IL-13 on cell-matrix
      interactions and epithelial shedding are unknown. We hypothesize that bronchial
      airway epithelial cells (BAEC) express paxillin, a structural focal adhesion
      protein, and downregulation of paxillin by Th2 cytokines lead to BAEC
      hyperpermeability. We showed by confocal microscopy the presence of paxillin in
      BAEC. We demonstrated by Western blot analysis that IL-4 and IL-13 stimulation
      results in downregulation of paxillin production. IL-4 and IL-13 stimulation
      decreased epithelial cell-matrix attachment as measured by electrical cell
      substrate impedance sensing system (ECIS). Our results suggest that Th2 cytokines
      IL-4 and IL-13 downregulate paxillin production by BAEC, thereby disrupting the
      cell-matrix interactions. This may help explain the epithelial shedding and
      epithelial membrane hyperpermeability that occurs in asthma.

PMID- 15163900
TI  - ANCA-GBM dot-blot: evaluation of an assay in the differential diagnosis of
      patients presenting with rapidly progressive glomerulonephritis.
AB  - Rapidly progressive glomerulonephritis (RPGN) is characterized by rapid and
      progressive loss of renal function and the presence of crescentic
      glomerulonephritis (CGN). Early diagnosis and appropriate treatment is mandatory
      to prevent death and/or renal failure. We have evaluated an ANCA-GBM dot-blot
      diagnostic test in terms of sensitivity, specificity, and inter-observer effect
      in consecutive patients with RPGN ( n = 82). Control sera ( n = 34) included
      healthy and relevant disease controls. Dot-blots were independently evaluated by
      nine observers. Proteinase 3 (PR3)-ANCA, myeloperoxidase (MPO)-ANCA, and both
      were detected by ELISA in 36, 32, and 3 samples of 71 patients with pauci-immune
      CGN, respectively. Two additional samples were ANCA negative. The dot-blot
      revealed a sensitivity of 92-95% for PR3-ANCA and 80-86% for MPO-ANCA. The
      specificity of the dot-blot for PR3- and MPO-ANCA was 100%. In the patients with
      anti-GBM nephritis ( n = 9) anti-GBM was detected by both ELISA and dot-blot
      (sensitivity: 100%). The specificity of the anti-GBM dot-blot was 91-94%.
      However, the inter-observer effect was relatively high for detection of anti-GBM
      antibodies (24%). In conclusion, the ANCA-GBM dot-blot is a useful screening tool
      in situations where conventional ANCA testing is not readily available with
      excellent performance for PR3-ANCA detection, but less optimal sensitivity for
      MPO-ANCA and specificity for anti-GBM detection. Therefore, it is recommended to
      include the following advises in the report to the physicians: 1) patients with a
      high clinical suspicion for MPO-ANCA-associated RPGN and negative dot-blot must
      have conventional analysis for MPO-ANCA, and 2) negative anti-GBM dot-blot makes
      anti-GBM disease very unlikely, but positive samples should be confirmed by
      conventional anti-GBM tests.

PMID- 15163901
TI  - A novel lymphocyte signaling defect: trk A mutation in the syndrome of congenital
      insensitivity to pain and anhidrosis (CIPA).
AB  - Congenital insensitivity to pain with anhidrosis is a syndrome characterized by
      loss of pain and sensation. The condition frequently evolves into deep wounds and
      prolonged healing times. Anhidrosis is another prominent component of the
      disorder. Often associated with recurrent episodes of unexplained fever, it can
      result in patient mortality. Recent investigations point to Trk A, the high
      affinity receptor for nerve growth factor (NGF), as a candidate for the site of
      the mutation that causes the disorder. Functional NGF receptors, such as Trk A
      and the Trk family of tyrosine kinases, are essential for NGF signaling of human
      lymphocytes. In this study, we demonstrated that the presence of a trk A mutation
      in patient B cells results in a novel lymphocyte signaling defect. In these B
      cells, NGF failed to induce Trk A phosphorylation, cytoskeleton assembly, or MAP
      kinase activation. These abnormalities may explain some of the clinical features
      of the disease.

PMID- 15163902
TI  - Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for
      monitoring the in vivo immune response to a HER2/neu vaccine in breast and
      prostate cancer patients.
AB  - HER2/neu is a proto-oncogene and a member of the epidermal growth factor receptor
      family of proteins that is overexpressed in numerous types of human cancer. We
      are currently conducting clinical trials with the HER2/neu E75 peptide vaccine in
      breast and prostate cancer patients. We have evaluated the use of HLA-A2 dimer
      molecule for the immunological monitoring of cancer patients receiving the E75
      peptide vaccine. Peripheral blood samples from patients receiving the vaccine
      were stained with HLA-A2 dimers containing the vaccine peptide E75 or control
      peptides and analyzed by flow cytometry. We compared the HLA-A2 dimer assay to
      standard methods of immunologic monitoring (IFN-gamma release, lymphocyte
      proliferation, and cytotoxicity). The HLA-A2 dimer assay was also compared with
      the HLA-A2 tetramer assay. E75 peptide-specific CD8 T cells were detected
      directly in the peripheral blood of patients by staining with E75-HLA-A2 dimers
      and CD8 antibodies. T cell cultures generated by repeated stimulations using E75
      peptide-pulsed dendritic cells showed increased staining with E75-peptide loaded
      HLA-A2 dimers. Simultaneously analysis by the dimer assay and standard
      immunologic assays demonstrated that the dimer-staining assay correlated well
      with these methods of immunologic monitoring. A direct comparison using E75
      specific HLA-A2 tetramers and HLA-A2 dimers for the detection of E75-specific CD8
      T cells in peripheral blood showed comparable results with the two assays. Our
      findings indicate that the HLA-A2 dimer is a powerful new tool for directly
      quantifying and monitoring immune responses of antigen-specific T cells in
      peptide vaccine clinical trials.

PMID- 15163918
TI  - [Genetics of diabetic complications: peripheral neuropathy].
AB  - Diabetic neuropathy is a common complication of type 1 and 2 diabetes mellitus.
      Chronic hyperglycaemia and/or insulin deficiency in the peripheral nerve lead to
      metabolic and vascular disturbances, responsible for the functional alterations
      and the characteristic histological abnormalities observed in the nerve fibre.
      Recently, genetic factors have been described, suggestive of a predisposition
      and/or a protective effect for diabetic neuropathy in certain patients. The
      search for these genetic factors through the study of polymorphism of gene
      involved in the various metabolic and vascular pathways, is currently increasing,
      but with contradictory results. The main studies and data are reviewed in this
      Article. The identification of candidate-genes should allowed, in the future, to
      better identify and manage diabetic patients at-risk for peripheral neuropathy.

PMID- 15163903
TI  - Tapasin decreases immune responsiveness to a model tumor antigen.
AB  - The T-cell response against cancer is dependent on the cell surface presentation
      of tumor-associated or tumor-specific peptides by major histocompatibility
      complex (MHC) class I molecules. We found that tapasin, a chaperone protein that
      normally assists in the assembly of MHC class I molecules, is undetectable in an
      unstimulated pancreatic tumor cell line, Panc02, and only very weakly expressed
      after gamma-interferon stimulation. Transfection of tapasin into the Panc02 cells
      did not quantitatively increase MHC class I surface expression or detectably
      affect MHC class I association with peptide and beta(2)-microglubulin (beta(2)m).
      However, we found that transfected tapasin downregulated immune reactivity
      against a model tumor antigen, MUC1. Although tapasin has been previously shown
      by others to increase immune recognition of particular antigens, our results
      suggest that tapasin has a negative impact on the presentation of an
      immunodominant epitope from a specific model tumor antigen.

PMID- 15163919
TI  - [Genetics of diabetic complications: nephropathy].
AB  - Diabetic nephropathy is present in 35 to 45% of Type 1 diabetic patients after 15
      20 yrs of diabetes duration. Glycaemic control and diabetes duration are the
      major risk factors for diabetic nephropathy. Hypertension which is twice as
      common in diabetics than in the general population, as well as ethnic origin play
      an important role too. However, as not all diabetic patients will develop
      diabetic nephropathy, this support the hypothesis for factors of genetic
      susceptibility (or of protection!) to diabetic nephropathy. Familial aggregation
      studies supporting this concept of genetic susceptibility, and studies on
      candidate genes polymorphisms and their association (or lack of association) with
      diabetic nephropathy (angiotensin-converting enzyme, angiotensinogen and atrial
      natriuretic peptide genes) are reviewed. Available data from candidate genes
      studies support a possible implication of vasoactive genes polymorphisms in the
      development of diabetic nephropathy, but the risk appears to be weak. Ongoing and
      future studies should aim to detect gene polymorphisms with strong effects, or to
      identify the association and/or interaction between polymorphisms and diabetic
      nephropathy.

PMID- 15163920
TI  - [Genetics of diabetic complications: retinopathy].
AB  - Multiple clinical and physiopathological studies as well as genetic analysis,
      suggest that diabetic retinopathy (DR) is a consequent of interactions between
      environmental factors, especially hyperglycaemia, and several genetic factors.
      The genes of aldose reductase (AR), inducible nitric oxide synthase (NOS2A),
      endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor
      (VEGF), pigmented epithelium-derived factor (PEDF), protein kinase C-beta (PKC
      beta) and receptor for advanced glycation end products (RAGE) implicated in the
      pathogenesis of DR. The only genetic marker associated with risk of DR in several
      studies is a microsatellite (A-C)n at 5'end of AR. The synergistic combination of
      conventional approaches (e.g. candidate gene association studies) with new
      emerging technologies (e.g. biochips) will be a key factor in the elucidation of
      the genetic aspects of DR.

PMID- 15163921
TI  - [Heart, diabetes and glitazones].
AB  - Beneficial metabolic effects of rosiglitazone are now well established and its
      adverse events, generally minor or mild well known too. Following a brief review
      of these metabolic effects and main adverse events, we mainly describe fluid
      retention (and edema) and the heart failure risk, their risk factors, clinical
      and diagnosis characteristics, possible pathophysiological mechanisms and the
      main preventive measures are reviewed. Numerous experimental data and/or
      preliminary studies in type 2 diabetic patients, including effects on
      cardiovascular risk factors or markers, justify to conduct a large prospective
      long term clinical program to assess rosiglitazone effects on cardiovascular
      morbidity and mortality in type 2 diabetic patients at high cardiovascular risk,
      these studies are briefly described.

PMID- 15163923
TI  - [Physical activity as a therapeutic tool in type 2 diabetes: the rationale].
AB  - Physical exercise is an important component of type 2 diabetes mellitus
      management. Acute physical exercise, on a day by day basis, has a clear
      hypoglycaemic effect. Physical exercise, on a regular basis at a sufficient
      level, has numerous favourable effects: improvement of glycaemic control (HbA1c)
      and insulin sensitivity, decrease of visceral fat mass, increase of skeletal
      muscle mass, favourable effects on various cardiovascular risk factors (arterial
      pressure, HDL-cholesterol, triglycerides, etc.). However, precise characteristics
      of physical exercise to be advised in type 2 diabetic patients (type of exercise,
      frequency, intensity, etc.) are still a matter of debates, as well as lack of
      practical guidance in/or differences between the various current recommendations.
      The crucial point, however, remains their feasibility, as well as the lack of
      long term patient's motivation and compliance which may partly explain the
      current low level of physical exercise observed in type 2 diabetic patients.

PMID- 15163922
TI  - [Adiponectin: from adipocyte to skeletal muscle].
AB  - Insulin resistance is characterized by a peripheral resistance to insulin
      mediated glucose uptake, and an hepatic resistance of glucose production to
      insulin. Insulin resistance in skeletal muscle is of a particular importance, and
      could be the consequence of an increase in intracellular and circulating fatty
      acids and triglycerides. Adipose tIssue plays an important role to regulate
      mobilization and release of fatty acids. Adipose tIssue is an endocrine organ
      which secretes several factors, including adiponectin. Adiponectin improves
      insulin sensitivity in skeletal muscle and liver, through a stimulation of fatty
      acid oxidation and glucose utilization. Thiazolidinediones enhance adiponectin
      expression and synthesis through PPARgamma, although the precise mechanism
      remains controversial. AMP-activated protein kinase (AMPK) is the main
      adiponectin target. Adiponectin, clearly, is a major modulator of glucose and
      lipid metabolism in insulin-sensitive tIssue and/or regulator of insulin
      sensitivity, in obese and/or glucose intolerant subjects, as well as in type 2
      diabetes mellitus. Recent works and the links between insulin resistance, adipose
      tIssue, adiponectin and its PPARgamma-enhanced secretion are reviewed in this
      paper.

PMID- 15163924
TI  - [Physical activity as a therapeutic tool in type 2 diabetes: practical aspects].
AB  - Physical activity is an integral part of the therapeutic management of type 2
      diabetic patients. Its beneficial effects on patients' metabolic control and
      quality of life are well recognized. The clinical intervention is based on two
      complementary approaches: to promote physical activity and/or to decrease
      sedentary behavior, with the aim of long term maintainance. Careful examination
      of the patient, and assessment of his/her physical capacity and potential risks
      associated with activity represent the first steps. Assessment of the patient's
      motivation and stage of change regarding physical activity appears to be a key
      element for the success of the physical activity project. Main objectives should
      be clearly defined, as well as the means to reach them (changes in every day-life
      activities, progressive structured physical exercise), and should be reevaluated
      and adapted on a regular basis, together with the patient, and whenever possible,
      with his/her familial/social environment.

PMID- 15163925
TI  - [Continuous glucose monitoring: which benefits?].
AB  - Continuous glucose monitoring is a recent technique which appears to be highly
      useful in diabetic patients, particularly in children and adolescents. Its
      potential interest to study unstable diabetes, to detect asymptomatic and
      nocturnal hypoglycaemias, to adapt and/or to adjust insulin treatment, etc. has
      lead to several recent clinical studies, conducted in various conditions. The
      different techniques, the studies conducted in children and adult diabetic
      patients, as well as the main current indications for continuous glucose
      monitoring are described in this article.

PMID- 15163926
TI  - [Clinical case: beliefs, Ramadan and diabetes mellitus].
AB  - From the clinical case of a 52-Year old, type 2 diabetic obese woman, muslim
      algerian native, an endocrinologist and a religious representative discuss the
      influences of religion, beliefs and environment, on compliance to the diabetes
      diet and therapeutic management, with a particular emphasis on the Ramadan
      period. Inadequate behaviours, result in a worsening in glucose control. This,
      should be avoided through an appropriate patient's education, all along the Year,
      not only through the healthcare team, but involving patient's family and friends
      too, as well as the community and religious Authorities.

PMID- 15163927
TI  - Prevention and control of influenza: recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - This report updates the 2003 recommendations by the Advisory Committee on
      Immunization Practices (ACIP) on the use of influenza vaccine and antiviral
      agents (CDC. Prevention and control of influenza: recommendations of the Advisory
      Committee on Immunization Practices [ACIP]. MMWR 2003;52[No. RR-8]:1-34). The
      2004 recommendations include new or updated information regarding 1) influenza
      vaccine for children aged 6-23 months; 2) vaccination of health-care workers with
      live, attenuated influenza vaccine (LAIV); 3) personnel who may administer LAIV;
      4) the 2004-05 trivalent inactivated vaccine virus strains: A/Fujian/411/2002
      (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Shanghai/361/2002-like
      antigens (for the A/Fujian/411/2002 (H3N2)-like antigen, manufacturers may use
      the antigenically equivalent A/Wyoming/3/2003 [H3N2] virus, and for the
      B/Shanghai/361/2002-like antigen, manufacturers may use the antigenically
      equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus); and 5) the
      assessment of vaccine supply and timing of influenza vaccination. A link to this
      report and other information regarding influenza can be accessed at
      http://www.cdc.gov/flu.

PMID- 15163928
TI  - Cigarette smoking among adults--United States, 2002.
AB  - One of the national health objectives for 2010 is to reduce the prevalence of
      cigarette smoking among adults to </=12%. To assess progress toward this
      objective, CDC analyzed self-reported data from the 2002 National Health
      Interview Survey (NHIS) sample adult core questionnaire. This report summarizes
      the results of that analysis, which indicated that, in 2002, approximately 22.5%
      of adults were current smokers. Although this prevalence is slightly lower than
      the 22.8% prevalence among U.S. adults in 2001 and substantially lower than the
      24.1% prevalence in 1998, the rate of decline has not been at a sufficient pace
      to achieve the 2010 national health objective. During 1983-2002, adults with
      household incomes below the poverty level and those with less than some college
      education consistently had higher smoking prevalence. A comprehensive approach to
      smoking cessation that comprises educational, economic, clinical, and regulatory
      strategies and emphasizes reducing disparities is required to reduce further the
      prevalence of smoking.

PMID- 15163929
TI  - Immunization registry progress--United States, January-December 2002.
AB  - Immunization registries are confidential, computerized information systems that
      collect vaccination data within a geographic area. By consolidating vaccination
      records from multiple health-care providers, generating reminder and recall
      notifications, and assessing clinic and vaccination coverage, registries serve as
      key tools to increase and sustain high vaccination coverage. One of the national
      health objectives for 2010 is to increase to 95% the proportion of children aged
      <6 years who participate (i.e., have two or more vaccinations recorded) in fully
      operational, population-based immunization registries. This report summarizes
      data from CDC's 2002 Immunization Registry Annual Report (2002 IRAR), a survey of
      registry activity among immunization programs in the 50 states and the District
      of Columbia (DC) that receive grant funding under section 317b of the Public
      Health Service Act. These data indicate that approximately 43% of children aged
      <6 years are enrolled in a registry; achieving the national health objective will
      require increased implementation of functional standards to improve data quality.

PMID- 15163930
TI  - Wild poliovirus importations--West and Central Africa, January 2003-March 2004.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, three
      World Health Organization (WHO) regions (Americas, European, and Western Pacific)
      have been certified polio-free, and the number of countries with endemic polio
      has decreased from 125 in 1988 to six in 2003 (Afghanistan, Egypt, India, Niger,
      Nigeria, and Pakistan). During January 2003-March 2004, importations of wild
      poliovirus (WPV) occurred in eight countries that were previously polio-free:
      five in the West African block (Benin, Burkina Faso, Cote d'Ivoire, Ghana, and
      Togo) and three in the Central African block (Cameroon, Central African Republic,
      and Chad), resulting in 63 polio cases. This report summarizes the 1)
      investigation and response to these WPV importations and 2) progress toward polio
      eradication in West and Central Africa.

PMID- 15163931
TI  - Noninvasive estimation of impaired hemodynamics for patients with acute
      myocardial infarction by Tei index.
AB  - BACKGROUND: Tei index, defined as the sum of isovolumic contraction and
      relaxation times divided by ejection time, has been proposed to express global
      left ventricular function. For patients with acute myocardial infarction (AMI),
      left ventricular function can potentially be a major determinant of hemodynamics
      with limited time for compensation, such as increased brain natriuretic peptide
      to attenuate congestion, and usually without any intervention to modify cardiac
      loading on arrival at the hospital during the acute phase. We, therefore,
      hypothesized that left ventricular function, expressed by the Tei index, allows
      noninvasive estimation of impaired hemodynamics for patients with AMI. METHODS:
      We studied 86 consecutive patients with first AMI (34 inferoposterior and 52
      anteroseptal). Tei index was obtained as: (a - b)/b, where a is the interval
      between the cessation and onset of mitral flow and b is the ejection time by
      aortic flow by pulsed Doppler echocardiography. By using pulmonary capillary
      wedge pressure (PCWP) > or = 18 mm Hg or <18 mm Hg and cardiac index (CI) < or =
      2.2 L/min/m(2) or > 2.2 L/min/m(2) by consecutive catheterization, patients were
      classified into 4 subsets: subset I with normal hemodynamics; subset II with
      elevated PCWP; subset III with reduced CI; and subset IV with both elevated PCWP
      and reduced CI. RESULTS: For patients with inferoposterior AMI, there was no
      significant correlation between the Tei index and PCWP or CI. For patients with
      anteroseptal AMI, however, the Tei index showed significant correlation both with
      PCWP (r = 0.59, P <.0001) and CI (r = -0.42, P <.01). Diagnosis of impaired
      hemodynamics (subset II-IV) by a Tei index > or = 0.60 showed a sensitivity,
      specificity, and accuracy of 86%, 82%, and 83%, respectively. CONCLUSIONS:
      Although the Tei index has limitations to evaluate hemodynamics in patients with
      inferoposterior AMI, the index allows approximate but quick and practical
      noninvasive estimation of impaired hemodynamics in patients with anteroseptal
      AMI.

PMID- 15163932
TI  - Effect of central hypothyroidism on Doppler-derived myocardial performance index.
AB  - BACKGROUND: Myocardial performance index (MPI) has been used to assess global
      ventricular function in different types of cardiac disease. Thyroid hormones
      influence cardiac performance directly and indirectly by changes in peripheral
      circulation. The aim of this study was to evaluate the possible effect of central
      hypothyroidism (CH) on MPI. METHODS: The study included 28 control subjects and 7
      patients with CH without cardiac disease. MPI was defined as the sum of
      isovolumetric contraction time (ICT) and isovolumetric relaxation time divided by
      ejection time. Patients were submitted to hormonal therapy with thyroxin and the
      study was repeated after 35 to 42 days. RESULTS: MPI was significantly higher in
      patients with CH (0.54 +/- 0.08) than in control subjects (0.40 +/- 0.05) (P
      =.002). The increase in MPI was caused by the prolongation of ICT without a
      significant variation of isovolumetric relaxation time and ejection time. After
      hormonal therapy there was a significant reduction of MPI (0.54 +/- 0.08 vs 0.42
      +/- 0.07; P =.028) and ICT. CONCLUSION: MPI was increased in patients with
      untreated CH. The increase was related to prolongation of ICT and reverted by
      hormonal therapy.

PMID- 15163933
TI  - Global longitudinal strain: a novel index of left ventricular systolic function.
AB  - BACKGROUND: Echocardiographic estimation of global left ventricular (LV) function
      is subjective and time consuming. Our aim was to develop a novel approach for
      assessment of global LV function from 2-dimensional echocardiographic images
      METHODS: Novel computer software for tissue tracking was developed and applied as
      follows: digital loops were acquired from apical 2-, 3-, and 4-chamber views and
      a line was loosely traced along the LV endocardium at the frame wherein it was
      best defined. Around this line, the software selected natural acoustic markers
      moving with the tissue. Automatic frame-by-frame tracking of these markers during
      the heart cycle yielded a measure of contractility along the selected region of
      interest. Global longitudinal strain (GLS) and GLS rate (GLSR) were calculated
      for the entire U-shaped length of LV myocardium (basal, mid, and apical segments
      of 2 opposite walls in each view). To test this software, computer-derived GLS
      and GLSR were analyzed by a nonechocardiographer, blinded to the
      echocardiographic interpretation, in 27 consecutive patients after myocardial
      infarction (MI) (age 64.4 +/- 12.9 years; 19 men; mean wall-motion score index of
      1.79 +/- 0.44) and compared with those obtained in 12 consecutive control
      patients (age 59.0 +/- 9.7 years; 8 women), with a normal echocardiographic
      study. RESULTS: GLS and GLSR, averaged from the 3 apical views, differed
      significantly in patients post-MI compared with control patients (GLS -14.7 +/-
      5.1% vs -24.1 +/- 2.9% and GLSR -0.57 +/- 0.21/s vs -1.02 +/- 0.09/s for patients
      post-MI vs control patients, respectively; both P <.0001). There was a good
      linear correlation between the wall-motion score index and the GLS and GLSR (R =
      0.68 and R = 0.67, respectively; both P <.0001). A cut-off value for GLS of -21%
      had 92% sensitivity and 89% specificity and a cut-off value for GLSR -0.9/s had
      92% sensitivity and 96% specificity for the detection of patients post-MI.
      CONCLUSIONS: GLS and GLSR are novel indices for assessment of global LV function
      from 2-dimensional echocardiographic images. Early validation studies with the
      method are suggestive of high sensitivity and specificity in the detection of LV
      systolic dysfunction in patients post-MI.

PMID- 15163934
TI  - Tachycardia during the valsalva maneuver: a sign of normal diastolic filling
      pressures.
AB  - Alteration of the loading conditions during the Valsalva maneuver is a helpful
      ancillary method in the noninvasive assessment of diastolic filling of the heart
      by Doppler echocardiography. When tachycardia is induced by the maneuver, mitral
      inflow velocity curves may become uninterpretable because of E velocity (the
      initial early diastolic velocity on the transmitral flow velocity curve) and A
      velocity (the velocity at atrial contraction on the transmitral flow velocity
      curve) wave fusion. To determine the clinical significance of the E velocity and
      A velocity wave fusion, our study assessed the relation between the heart rate
      response induced by the Valsalva maneuver and the left ventricular filling
      pressures measured during cardiac catheterization. In all, 77 patients performed
      the maneuver during continuous hemodynamic and electrocardiographic monitoring.
      The ratio between the baseline R-R interval and the shortest R-R interval during
      the maneuver was calculated. A ratio value higher than 1.1 was predictive of a
      pre-A pressure of less than 18 mm Hg (94% positive predictive value). Reflex
      tachycardia during the Valsalva maneuver and subsequent fusion of the E velocity
      and A velocity waves on the mitral velocity curves is a sign of normal left
      ventricular filling pressures.

PMID- 15163935
TI  - Are there sex differences in regional systolic function and wall stress in
      hypertrophic obstructive cardiomyopathy? A three-dimensional echocardiography
      study.
AB  - OBJECTIVES: Sex-related differences in left ventricular (LV) systolic function
      have been previously reported in patients with aortic stenosis and hypertensive
      heart disease. The goal of this study was to determine systolic function of the
      LV in male and female patients with hypertrophic obstructive cardiomyopathy and
      to relate it to wall thickness and wall stress, respectively. BACKGROUND: Wall
      thickening, a parameter of regional systolic function, is determined by wall
      thickness and wall stress. A comprehensive analysis of regional LV function was
      performed from multiplane transesophageal echocardiography with 3-dimensional
      reconstruction of the LV. METHODS: In 21 patients (11 men and 10 women) 4
      parallel (2 basal and 2 apical) equidistant short-axis cross sections from base
      to apex were obtained from the reconstructed LV. In each short axis, 24 wall
      thickness measurements were carried out in 15-degree intervals at end-diastole
      (ED) and end-systole. Thus, a total of 192 measurements were obtained in each
      patient. Wall thickening, a parameter of regional systolic function, was
      calculated as the difference of ED and end-systolic wall thickness, and
      fractional thickening as thickening divided by ED thickness. RESULTS: Fractional
      thickening and wall stress were inversely related to ED wall thickness in both
      men and women. Women showed better LV systolic function when compared with men (P
      <.001). However, when corrected for wall stress, which was lower in women, there
      was no sex difference in systolic function. CONCLUSIONS: There are regional
      differences in LV systolic function in men and women that depend on regional wall
      thickness and wall stress.

PMID- 15163937
TI  - Assessment of infarct size and myocardial function in mice using transesophageal
      echocardiography.
AB  - BACKGROUND: Because transthoracic echocardiography (TTE) has significant
      limitations in assessing changes consequent to myocardial infarction (MI) in
      mice, we studied two novel methods to characterize such infarcts. METHODS: Large
      MIs were produced by proximal left coronary artery ligation, and small MIs by
      distal left coronary artery ligation. Serum cardiac troponin I levels were
      measured 24 hours postoperatively. At 2 weeks, mice underwent transesophageal
      echocardiography (TEE) and TTE. Infarct sizes were determined histologically.
      RESULTS: Surviving mice were classified according to infarct size. TEE identified
      all histologically proven large infarcts, and 4 of 5 small infarcts. TTE
      identified 4 of 5 large infarcts, but only 1 of 5 small infarcts. TEE-derived
      fractional area change, but not TTE-estimated left ventricular fractional
      shortening, was significantly different among large, small, and sham infarcts.
      Cardiac troponin I showed excellent correlation with infarct size and mortality.
      CONCLUSIONS: Cardiac troponin I was found to predict infarct size and mortality,
      whereas TEE proved superior to TTE in determining infarct size and/or myocardial
      function in a murine MI model. These tools should provide more accurate
      assessments in preclinical studies of ischemic cardiomyopathy.

PMID- 15163936
TI  - Left atrial volume and the risk of paroxysmal atrial fibrillation in patients
      with hypertrophic cardiomyopathy.
AB  - Paroxysmal atrial fibrillation (PAF) is a common complication of patients with
      hypertrophic cardiomyopathy, often leading to acute or progressive heart failure
      and cerebral infarction. We assessed the echocardiographic data of 141
      consecutive patients with hypertrophic cardiomyopathy, with and without PAF. In
      all, 31 patients (22%) had a history of PAF with spontaneous conversion to in
      sinus rhythm. Left atrial volume and left atrial volume indexed to body surface
      area were significantly increased for patients with PAF compared with those
      without PAF. Maximum left atrial volume was the most sensitive and specific
      parameter for the occurrence of PAF in patients with hypertrophic cardiomyopathy.

PMID- 15163939
TI  - Effects of coil closure of patent ductus arteriosus on left anterior descending
      coronary artery blood flow using transthoracic Doppler echocardiography.
AB  - Transthoracic Doppler echocardiography provides noninvasive measurements of
      coronary blood flow in the left anterior descending coronary artery (LAD). This
      method has the potential to show the effects of acute changes in loading
      conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a
      model of acute changes in blood pressure and left ventricular (LV) preload that
      influences coronary blood flow. We applied this technique to assess the coronary
      blood flow changes for patients with PDA before and immediately after PDA coil
      closure. We examined 9 patients (1.8 +/- 1.1 years) with simple PDA and 8 age
      matched healthy children. LV dimensions and LV mass were measured. Maximum peak
      flow velocity and flow volume in the LAD were measured. Pulmonary to systemic
      flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil
      closure, LV end-diastolic dimension decreased, and systolic and diastolic blood
      pressures increased significantly. The maximum peak flow velocity, LAD flow
      volume, and the ratio of LAD flow volume to LV mass increased significantly. The
      changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass
      (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In
      5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared
      with control subjects, but they increased to normal values after coil closure of
      PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting
      in improvement of myocardial perfusion. These findings provide new insights into
      the relationship between cardiac function and coronary circulation in pediatric
      patients with heart diseases associated with PDA.

PMID- 15163938
TI  - Noninvasive vessel-selective perfusion imaging with intravenous myocardial
      contrast echocardiography.
AB  - BACKGROUND: Intravenous myocardial contrast echocardiography (MCE) cannot
      identify each perfusion area of coronary vessels separately. However, by
      destroying microbubbles passing through a specific vessel using high-power
      ultrasound during intravenous MCE, vessel-selective perfusion imaging (VSPI) may
      be feasible. METHODS: In 10 open-chest dogs, intermittent short-axis images were
      obtained during contrast agent infusion using an ultrasound system. For VSPI, a
      probe coupled to another ultrasound machine was placed on the proximal left
      circumflex coronary artery (LCx). High-power ultrasound pulses were transmitted
      to destroy bubbles passing through the LCx. A negative contrast area on VSPI was
      considered to represent the perfusion area of the LCx (LCx-VSPI). A negative
      contrast area on conventional MCE during LCx occlusion and a region without
      staining by Evans blue dye were used as gold standards for defining the LCx
      perfusion area. LCx-VSPI was compared with a negative contrast area on
      conventional MCE during LCx occlusion and a region without staining by Evans blue
      dye. RESULTS: Despite lack of LCx occlusion, high-power destructive pulses
      produced a definite area of negative contrast on the LCx region. Decreased power
      of ultrasound pulses resulted in disappearance of the negative contrast area. An
      excellent relationship was demonstrated between both LCx-VSPI and a negative
      contrast area on conventional MCE during LCx occlusion (r = 0.93, P <.0001), and
      LCx-VSPI and a region without staining by Evans blue dye (r = 0.92, P =.0002).
      CONCLUSION: VSPI during intravenous MCE may be feasible for noninvasive
      assessment of perfusion areas associated with specific vessels.

PMID- 15163940
TI  - Are all echocardiographic findings equally predictive for diagnosis in prosthetic
      endocarditis?
AB  - OBJECTIVE: The purpose of this study was to analyze the predictive value of
      different anatomic echocardiographic findings for diagnosis of prosthetic
      endocarditis. BACKGROUND: Prognosis in endocarditis has improved in recent years
      after the wide acceptance of new clinical diagnostic criteria. One of the most
      important issues in clinical diagnosis is to use echocardiography for
      identification of endocardial involvement, but prosthetic material impairs echo
      quality. METHODS: In all, 49 patients with 58 episodes of suggested prosthetic
      endocarditis were prospectively studied using transthoracic and transesophageal
      echocardiography. The patients were divided into two groups: group A, patients
      with 34 episodes of definite endocarditis according to Durack's criteria; and
      group B, patients with 24 episodes who were eventually classified as not having
      endocarditis, either by surgical exploration or by a mean of 32.6 months (range:
      8-38 months) of follow-up. RESULTS: In group A, valve dehiscence was observed in
      4 episodes of suggested endocarditis, pseudoaneurysms in 3, fistulae in 2, and
      moderate to severe perivalvular regurgitation in 15. No patient in group B had
      these abnormalities (P <.001). Vegetations were present in 17 episodes in group A
      (50%) versus 1 in group B (9%; P <.001); perivalvular abscesses were seen in 19
      episodes in group A (56%) versus 1 in group B (P <.001). Mild perivalvular
      regurgitation was observed in only 1 episode for group A (3%) and in 14 episodes
      for group B (58%; P <.01). The presence of any of the above echocardiographic
      finding, when used in combination with the exclusion of mild perivalvular
      regurgitation, had a positive and negative predictive value for diagnosing
      endocarditis of 94% and 96%, respectively. Isolated mild perivalvular
      regurgitation had a poor positive predictive value (6%). CONCLUSION: Isolated
      mild perivalvular regurgitation should not be used as diagnostic criteria in
      patients with suggested prosthetic valve endocarditis.

PMID- 15163941
TI  - Feasibility of remote echocardiography with satellite transmission and real-time
      interpretation to support medical activities in the austere medical environment.
AB  - Echocardiography is an essential tool in the evaluation of patients with cardiac
      emergencies and chest trauma. The objective of our study was to establish the
      feasibility and diagnostic accuracy of a portable satellite transmission system
      in the assessment of cardiac emergencies for the real-time support of mass
      casualty and humanitarian relief efforts. Twelve patients with various degrees of
      cardiac structural disease identified by conventional inhospital transthoracic
      echocardiography were transported to a remote portable field hospital where
      transthoracic echocardiography was performed with a handheld echocardiographic
      device. Images were then relayed by a commercial satellite to a level III trauma
      center where they were interpreted in real time by a cardiologist. Remote studies
      were recorded at the field hospital before satellite transmission and again on
      download at the receiving facility. The remotely acquired studies before and
      after satellite transmission were compared with each other and subsequently
      compared with conventional hospital transthoracic echocardiograms for technical
      quality and diagnostic accuracy using a blinded, single-reader, side-by-side
      comparison. Excellent agreement was found between the recorded field-site and
      satellite-transmitted images with an overall average of 95% concordance. When the
      field data acquired with the handheld device and satellite transmission were
      compared with conventional inhospital echocardiography, a high degree of
      agreement was demonstrated in overall technical quality (83%) and assessments of
      left ventricular ejection fraction (100%), pericardial effusion (100%), and left
      ventricular size (92%). This study demonstrates the feasibility and diagnostic
      accuracy of remote, real-time echocardiography using satellite transmission for
      mass casualty triage or humanitarian relief efforts.

PMID- 15163942
TI  - Intrapericardial carcinoid metastasis.
AB  - Carcinoid tumors are malignancies of neuroendocrine tissue. Metastasis, most
      commonly to the liver, is associated with the carcinoid syndrome characterized by
      secretory symptoms and right-sided valvular heart disease. We report a case of
      previously unidentified pericardial metastasis, in the absence of any valvular
      disease, thus, reflecting an unusual cardiac complication of this tumor. A 50
      year-old patient with histologically confirmed carcinoid syndrome underwent
      screening transthoracic echocardiography that demonstrated a large mass posterior
      to the interatrial septum. The location of this mass was confirmed by
      transesophageal echocardiography and magnetic resonance imaging to be entirely
      within the pericardial space without evidence of myocardial involvement. The mass
      was removed at thoracotomy and histology confirmed metastatic carcinoid disease.
      Although patients with carcinoid syndrome are at risk of cardiac valvular
      complications, and should be screened, this case demonstrates an unusual and
      previously unidentified site of metastatic disease.

PMID- 15163943
TI  - Noncompacted myocardium in Ebstein's anomaly: initial description in three
      patients.
AB  - Exercise intolerance in Ebstein's anomaly is usually attributed to desaturation
      secondary to right-to-left shunting as a result of a small or distorted left
      ventricle (LV), significant tricuspid valve regurgitation, right ventricular
      dysfunction, or a combination of these. We observed one boy (age 15 years) and
      two women (ages 20 and 29 years) with severe Ebstein's anomaly and strikingly
      abnormal LV myocardium resembling the features described for LV noncompaction. LV
      size and systolic function were normal in the two women; the boy had a dilated LV
      with severely diminished ejection fraction. The LV myocardium was found to be
      unusually coarse and hypertrabeculated, with small intertrabecular recesses and
      an irregular endocardial surface. The findings in these 3 patients represent the
      whole spectrum of mild to severe LV noncompaction. Diastolic dysfunction was
      present in 2 of the 3 patients. Exercise tolerance was diminished in all. There
      was no mitral or aortic valve disease. The 15-year-old boy underwent heart
      transplantation 6 months later for biventricular failure. Thus, Ebstein's anomaly
      does not seem to be a pathology confined to the right ventricle, but may rarely
      lead to LV noncompacted myocardium. This LV pathology may be an additional
      explanation for exercise intolerance or signs of left heart failure in patients
      with Ebstein's anomaly.

PMID- 15163945
TI  - Using imaging for cardiovascular risk prediction: an overview.
AB  - Atherosclerosis is a systemic, silent, and deadly disease; however, primary risk
      reduction is very effective. Cost-effective risk modification relies on accurate
      and individualized risk stratification; however, traditional risk factor-based
      assessments fail to account for individual progression along the pathophysiologic
      continuum. Ultrasound and other imaging techniques that measure both anatomy and
      function provide well-validated surrogate markers for atherosclerosis that have
      incremental predictive power to that provided by risk factors, and may be useful
      in designing primary prevention strategies.

PMID- 15163946
TI  - Carotid intima-media thickness and vascular age: you are only as old as your
      arteries look.

PMID- 15163947
TI  - Carotid intima-media thickness testing: technical considerations.

PMID- 15163948
TI  - Brachial artery reactivity: clinical tool or research toy?

PMID- 15163949
TI  - Ultrasound brachial artery reactivity testing: technical considerations.

PMID- 15163950
TI  - Going for the money: Transthoracic assessment of coronary artery flow reserve.

PMID- 15163951
TI  - Noninvasive assessment of coronary flow reserve by echocardiography: technical
      considerations.

PMID- 15163952
TI  - Evaluation of left ventricular filling pressures by the Tei index.

PMID- 15163954
TI  - Where is the informed consumer?

PMID- 15163955
TI  - Courts review last chance employment agreements.

PMID- 15163958
TI  - Disease management: breaking down silos to improve chronic care.

PMID- 15163956
TI  - Women's health trends and National Institutes of Health centers on research in
      women's health.

PMID- 15163959
TI  - Incorporating life care planning concepts in case management.

PMID- 15163960
TI  - Music therapy--the rhythm of recovery.

PMID- 15163961
TI  - Making the best home care referral.

PMID- 15163962
TI  - Ensuring quality of highest-risk population care management in a teleworking
      environment.

PMID- 15163963
TI  - A winning team.

PMID- 15163964
TI  - [The quality of life of patients with chronic lower limb ischemia].
AB  - Sixty-six patients with chronic lower limb ischemia (CLLI) were examined. The
      mean age of the patients constituted 55.98+/-7.7 (from 39 to 75 years). There
      were 64 (96.9%) men and 2 (3.1%) women. According to the runoff, the patients
      were distributed in the following way. Twenty-eight (41.8%) patients demonstrated
      good runoff, 23 (34.855) satisfactory, and 15 (23.2%) patients had poor runoff
      (according to the classification proposed by R.B.Rutherford). As dependent on the
      stage of ischemia the patients were divided into 2 groups. Twenty-eight (42.5%)
      patients presented with intermittent claudication (stage IIB) and 38 (57.5%)
      patients suffered from critical ischemia (st. III-IV). The quality of life (QL),
      was assessed using a SF-36 questionnaire and a questionnaire for patients with
      CLLI. After vascular reconstruction the QL of patients with infrainguinal artery
      lesion remained significantly low according to the majority of parameters as
      compared to the normal population. However, comparatively to the preoperative
      parameters, the QL after operation was significantly improved in all the
      indicators. The QL of patients with a clinical improvement after operation
      significantly differed from that in the patient group with a history of
      unsuccessful operation. In the long-term period, the QL of patients with bypass
      thrombosis was considerably worse in all the parameters than in patients with
      patent bypasses. As for the parameters of both questionnaires, the QL of patients
      with an amputated lower limb was appreciably worse than in patients with saved
      limbs.

PMID- 15163965
TI  - The importance of D-dimer for the diagnosis of venous thromboses in clinical
      cardiology.
AB  - The aim of the study was to analyze the importance of the rapid assay for D-dimer
      in the diagnosis of venous thromboses (VT). The study accrued 82 patients. There
      were 57 (70%) men and 25 (30%) women aged 16 to 86 years. Fifty-three patients
      were suspected of deep venous thrombosis (DVT) and 29 of pulmonary
      thromboembolism (PTE). In 49 of the 82 patients, the use of USD, isotope
      phlebography, x-ray and ventilation-perfusion scintigraphy of the lungs made it
      possible to verify the diagnosis of VT. In one case, it was verified on autopsy.
      In 33 patients, the suspicions were rejected. The blood assay for D-dimer was
      performed using the kit Roche/Diagnostika Stago. The method is based on
      agglutination of latex particles covered by monoclonal antibodies to D-dimer.
      Among the 49 patients with a verified diagnosis of VT, D-dimer was positive in 44
      (89.8%) and negative in 5 (11.4%) patients. In the group of the 33 patients, in
      whom the diagnosis of VT was rejected, D-dimer was negative in 26 (78.8%) and
      positive in 7 (21.8%) patients. Thus, the sensitivity of the assay for D-dimer
      constituted 89.8% and the specificity 78,8%. The high sensitivity of the assay
      provides an opportunity of using D-dimer measurement as a screening method in
      patients suspected of VT. Negative D-dimer is helpful in excluding VT. If D-dimer
      is positive, the diagnosis should be confirmed by other methods.

PMID- 15163967
TI  - [Endovascular surgery in the treatment of patients with myoma uteri].
AB  - Forty patients with myoma uteri of varying sites were treated by the new little
      invasive method - embolization of the uterine arteries. All the patients were
      admitted to the clinic with the symptoms of the high menstrual blood loss or
      functional disorders of the pelvic organs. Embolization of the uterine arteries
      made it possible to achieve good clinical results marked by minimization or
      removal of the clinical manifestations of myoma uteri.

PMID- 15163966
TI  - [The role of matrix metal proteinases in the development of restenoses after
      transcutaneous coronary interventions].
AB  - Endovascular coronary interventions for CAD induce restenoses in 20-50% of
      patients after 3-6 months. Following angioplasty or stenting restenosis arises
      from constrictive remodeling of the arterial wall and intimal hyperplasia. The
      damaged arteries provoke migration and proliferation of smooth muscle cells as a
      result of which there forms the neointima with accumulation of the extracellular
      matrix in the arterial intimal layer. These processes are regulated by matrix
      metal proteinases (MMP) and their tissue inhibitors. The rise of the MMP level in
      the dilated coronary arteries leads to vascular remodeling and formation of
      restenosis due to the effect on vascular smooth cell migration and thrombosis.

PMID- 15163968
TI  - [Use of covered stent grafts in treatment of embolism-threatening stenoses and
      arterial occlusions].
AB  - The present work was aimed at demonstrating possibilities and prospects of using
      covered stent grafts in treatment of patients with embolism-hazardous parietal
      thrombi, embolism-endangered stenoses, and occlusions of peripheral arteries.
      Using stent grafts covered with non-woven materials, including PTFE films
      ("Hemobahn endograft" and "JOSTENT Peripheral Stent Graft") in the arteries of
      the iliac and femoropoplietal segments, makes it possible to avoid not only acute
      and delayed occlusions, but to use a PTFE-covered stent graft as a means of
      isolating the intima from the blood flow, as a method of "inhibiting" intimal
      hyperplasia in the stented arterial segment. The article deals with clinical
      follow-ups of patients with embolism-dangerous atherosclerotic stenoses and
      occlusions of iliac arteries, who underwent successful implantation of covered
      stents into the affected segments of the arterial bed. These findings
      demonstrably show high efficacy of using methods of endografting in clinical
      situations wherein surgical treatment is associated with increased risk.

PMID- 15163969
TI  - [Color duplex scanning in morphological and functional assessment of lower limb
      arterial occlusions].
AB  - The paper assesses a potential of color duplex scanning (CDS) in topical
      diagnosis of atherosclerosis-related lower limb arterial occlusions (LLAO).
      Benefits and drawbacks of CDS are compared with those of digital subtraction
      arteriography (DSA). The authors describe objective quantitative measurement of
      ischemic grade or lower limb chronic arterial insufficiency due to
      atherosclerosis-related occlusions according to the magnitude of resistance or
      Pourcelot index (RI). Comparative effectiveness of CDS and DSA are evaluated on
      the base of 100 patients (791 arterial segments) examination with subsequent
      calculation of CDS sensitivity, specificity, diagnostic accuracy and validity.
      Correlation is drawn between ischemic grade and RI in tibial and dorsal
      metatarsal arteries. It is concluded that CDS plays an important role in topical
      diagnosis of LLAO, in graft patency evaluation and decision for future
      interventions. CDS can be used for objective measurement of limb ischemic grade.
      RI value appears to be a valid criterion for functional assessment of lower limb
      ischemia. Yielded with the help of CDS anatomic and hemodynamic data restrict
      indications for invasive, costly and radiation-related DSA.

PMID- 15163970
TI  - [Long-term hemodynamic characterization of distal anastomoses after aortofemoral
      reconstruction].
AB  - Duplex scanning was used to characterize the qualitative and quantitative
      parameters of blood flow in portofemoral bypasses and distal anastomoses in the
      long-term (3- 144 months) period after operation. In 50% of cases with an end-to
      side anastomosis, the examination reverled arterial segment occlusions caudal to
      the anastomosis. 12.5% of patients showed the maintenance of antegrade blood flow
      in the native arteries (parallel with the bypass). Retrograde blood flow through
      the anastomosis was recorded only in 32.5% of cases. As a rule, it was restricted
      by 1-2 branches of the external iliac artery, reaching the internal iliac artery
      only in 5% of cases. After one year the cumulative retrograde patency of the end
      to-side anastomoses constitute 59.1+/-7.2% and after 5 years it is equal to
      18.6+/-9.9%. If the superficial femoral artery was patent, the volume blood flow
      in the bypass was higher. The rise of the volume blood flow was also induced by
      the presence of the retrograde patency of the anastomosis which was apparently
      linked with the origination of an additional runoff pool. This advantage is
      especially completely realized when the condition of the distal perceptive bed is
      poor.

PMID- 15163971
TI  - The first experience with minimally invasive phlebectomy using the TriVex system.
AB  - Presented herein is the first experience gained in Russia with endoscopic
      transillumination phlebectomy (ETP). The aim of the study was to evaluate the
      clinical effectiveness and advantages of ETP versus traditional combined
      phlebectomy (TCP). Altogether 94 patients with different forms of lower extremity
      varicosis were operated on. Before operation the patients underwent Doppler
      ultrasound and duplex scanning. The main group included 47 patients who were
      operated on by ETP. The control group comprised 47 patients provided TCP. The ETP
      technique is based on hydraulic dissection of varicose veins which is attained by
      injection of a special solution under a pressure of 400-500 mm Hg, using an
      illumination irrigator inserted to subcutis via 2-3 mm punctures. Besides ETP is
      based on the effect of transillumination allowing to determine not only a precise
      location of varicose veins but also to control their drastic ablation by means of
      a special resector. To compare the above-indicated two techniques, the following
      parameters were studied: the time of operation, the number of incisions, the
      intensity of postoperative painful syndrome and the cosmetic effect according to
      the analog scales. The results obtained have shown that the use of ETP
      considerably decreased the time of operation; there was a substantial lowering of
      the number of incisions and punctures due to which the duration of postoperative
      painful syndrome decreased. Since the operation is performed via minipunctures
      which are closed by surgical plaster, an excellent cosmetic result is obtained.
      The first experience with ETP has demonstrated that this technique compares very
      favourably with TCP. The labor intensity of operation is minimized. Permanent
      visual control over vein extraction during operation makes it possible to
      appreciably raise the radicalness of intervention. The possibility of performing
      operation via minipunctures guarantees a more uneventful postoperative course and
      an excellent cosmetic result. So, ETP is a modern promising and a minimally
      invasive method for the treatment of varicose veins of the lower extremities. It
      requires extensive application with referral to one-day hospital.

PMID- 15163972
TI  - [Ginkor Fort for management of lower limb chronic venous insufficiency].
AB  - Considering current knowledge on pathogenesis of lower limb chronic venous
      insufficiency, the authors substantiate the necessity of drug therapy in
      phlebological practice. The use of combined drug Ginkor Fort - representative of
      a new polyvalent venotonics - is described. The need of large-scale clinical
      trials with adequate objective control is stressed.

PMID- 15163973
TI  - [The potential of conservative therapy and surgical treatment of microcirculatory
      distress in chronic venous insufficiency of the lower extremities in a stage of
      trophic disorders].
AB  - The present work describes the results of an all-round examination and treatment
      of 120 patients suffering from different forms of chronic venous insufficiency
      (CVI) of the lower extremities with trophic disorders of soft tissues. Of these,
      varicosis was present in 91 (75.8%) patients and postthrombotic disease - in 29
      (24.2%), patients. Hemomicrocireulation was examined by laser Doppler flow-metry.
      Assessment was made of the functional activity of neutrophilic granulocytes of
      the microcirculatory bed. The data were obtained indicating the decrease of skin
      perfusion and activation of neutrophils in the hemomicrocirculatory bed of the
      involved extremity at venous outflow decompensation. Of the 120 persons,
      conservative treatment was provided to 23 patients, in 45 patients, the
      conservative measures represented a stage in the preoperative preparation. Ninety
      seven patients were operated on. The studies of hemomicrocirculation carried out
      at different times after treatment have demonstrated that conservative treatment
      produces a beneficial effect on hemomicrocirculatory disorders in the lower
      extremities of patients with CVI. However, the effects of conservative therapy
      are unstable and not long-lasting. Surgical correction of the venous outflow in
      patients with decompensated forms of CVI of the lower extremities leads to a
      stable improvement of the functional parameters of microcirculation.

PMID- 15163974
TI  - [Real embologenicity of thromboses of lower extremity veins].
AB  - The aim of the present work was to study real embologenicity of thromboses of
      lower extremity veins. We carried out a comparative evaluation of the embologenic
      risk of different thromboses of the superficial and deep veins associated with
      hospital treatment. The study performed allows the following conclusions to be
      drawn: venous thromboses in the system of the inferior vena cava are marked by an
      unpredictable course and require the follow up of the thrombotic process and
      active conservative treatment within the period not less than 7 days from the
      time of the first manifestations of thrombosis; thrombosis of the femoral vein as
      well as thrombosis of the sural veins have the highest embologenic risk (6.45 and
      6.25%, respectively). Patients with ascending thrombophlebitis of the greater
      saphenous vein remain at high risk for embologenic process and require urgent
      operation.

PMID- 15163975
TI  - [Varicosis of the lower extremities as a consequence of connective tissue
      dysplasia].
AB  - An analysis was made of two groups of patients presenting with varicosis. The
      first group comprised 82 patients aged 15 to 30 years without risk factors. The
      second group accrued 85 patients with traditional risk factors: pregnancy and
      birth, overweight, considerable dynamic and physical loading, age from 30 to 50
      years, and intake of hormonal contraceptives. It has been established that the
      key role in the development of varicosis is played by connective tissue dysplasia
      (CTD), the intensity of which predetermines the origination of phlebopathy and
      varicosis as well as the rate of their progression. The most frequently occurring
      is the mechanism of the development of phlebopathy as structural and functional
      defectiveness of all venous vessels of the extremity, leading to the rise of the
      deposited blood volume in the leg because of the high elasticity of venous walls.
      Secondly, CTD that initially impairs valve morphology, results in local varicosis
      under the effect of reflux hydrodynamic strokes at the weakened venous wall.

PMID- 15163976
TI  - [The long-term results and indications for use of Gore-Texgrafts in the
      femoropopliteal position in patients with atherosclerotic lesion of lower limb
      arteries].
AB  - Presented herein are the long-term results of femoropopliteal reconstructions
      above the knee joint fisure in patients with atherosclerotic lesion of the
      femoropopliteal segment using Gore-Tex grafts. The retrospective study accrued
      108 patients. Of these, IIB degree lower limb ischemia (according to the A.V.
      Pokrovsky classification) was initially present in 64 (60.2%) and critical
      ischemia in 52 (40.8%) patients. Patients suffering from lower limb ischemia of
      varying degree did not significantly differ in the age or coexistent diseases.
      The mean value of the ankle/brachial index (ABI) accounted for 0.46+/-0.23 in
      patients with IIB degree ischemia and for 0.40+/-0.27 in patients with critical
      lower limb ischemia. All the patients were evaluated for the condition of the
      distal bed according to the scheme proposed by Rutherford et al. in 1997. The
      patients were distributed into three groups: patients with "good" runoff (from 1
      to 4 points, n=65), patients with "satisfactory" runoff (from 5 to 7 points,
      n=36), and those with an "unsatisfactory" condition of the distal bed (runoff
      point over 7, n=7). The long-term results were assessed in 81 (75%) patients over
      the period as long as 105 months. The mean follow up accounted for 58,4 months.
      One year later the graft patency in the total patient group constituted 73.1%,
      after 3 years it was equal to 54.8%, and after 5 years to 49.9%. It is
      demonstrated that the initial runoff point exerted a significant effect on the
      graft patency. It is noteworthy that in patients with an initially "good" runoff
      point, 57.5% of the grafts were patent 5 years after operation whereas in
      patients with a "satisfactory" point only 35.3% turned out patent (p<0.05).
      Patients with an initially "unsatisfactory" runoff point developed thrombosis of
      all grafts over the period as long as 6 months following operation. The five-year
      limb salvage was observed in 77.6% of patients. It has been revealed over the 5
      year period that the degree of initial limb ischemia did not produce any
      significant effect on the graft patency or limb salvage. The scheme for runoff
      assessment allows to define in a differentiated way the indications for use of
      Gore-Tex grafts in the femoropopliteal position. The runoff point had a
      significant effect on the long-term 5-year patency of the grafts.

PMID- 15163977
TI  - Multiyear experience in endoscopic thoracic sympathectomy.
AB  - The results of endoscopic thoracic sympathectomy performed for 787 patients
      during a 30-year period are presented. Six hundred seventy three patients were
      operated on for upper limb arterial occlusion of distal and diffuse type,
      Raynaud's disease or syndrome, 7 patients - for causalgic pain in upper limbs and
      Sudeck's syndrome, 85 - for hyperhidrosis. Twelve patients underwent lower
      thoracic sympathectomy for painful chronic pancreatitis, 4 - total destruction of
      thoracic sympathetic trunk due to pernicious hypertension of unknown origin, and
      6 - endoscopic thoracic sympathectomy for acute thrombosis of upper limb arteries
      with distal circulation impairment. Immediate positive effect of interventions
      was detected in all cases except for acute arterial thrombosis. One patient died
      postoperatively due to arrhythmia-related cardiac arrest. Postoperative
      complications - lung border damage and intercostal vascular hemorrhage - were
      detected in 0.2% of cases. Increased air effusion from pleural cavity and
      intercostal neuralgia were observed postoperatively in some cases but did not
      require any special management. Long-term outcomes were followed up for period of
      5-10 years, 72.7% of monitored patients had stable positive outcomes. Our
      experience has demonstrated that endoscopic thoracic sympathectomy is a safe,
      minimally invasive and effective intervention for upper limb chronic arterial
      insufficiency of distal and diffuse type or for hyperhidrosis.

PMID- 15163978
TI  - [Surgical management of patients with multifocal atherosclerosis].
AB  - One-stage reconstructions on the brachiocephalic and lower limb arteries are most
      often linked with a risk of perioperative acute coronary insufficiency.
      Retrospective analysis of the results of surgical treatment of this group of
      patients has demonstrated an opportunity of successful simultaneous operations
      when performing aortofemoral reconstructions from the mini-laparotomy access.
      This is ensured by minimization of surgical trauma, blood loss and the time of
      operation. Provided the coronary reserve of the heart is appreciably lowered, it
      is advisable that one-stage operation may be declined.

PMID- 15163979
TI  - [Endothelial vascular grafts (Experimental research)].
AB  - The authors present herein their findings obtained in bench-test and experimental
      studies, which made it possible to work out an original technology of creating an
      endothelial covering of the inner surface of vascular grafts made of
      polytetrafluorethylene. The new technology includes the definite sequential
      processes which are as follows: 1) creation of vascular endotheliocytes; 2)
      stimulation of growth and reproduction of endotheliocytes; 3) preparation of the
      graft, including creation of stable positive potential on its inner surface in
      order to create optimal conditions for endothelization; 4) graft endothelization
      itself. In order to assess efficacy of endothelial vascular grafts, we carried
      out a total of 105 experiments on dogs. The experimental conditions made it
      possible to comparatively study the standard and endothelialized grafts using
      them in the position of the aortic abdominal portion, carotid and femoral
      arteries. The new grafts turned out to possess satisfactory performance
      properties, which precluded formation of thromboses and hyperplasia of the
      noeintima, simultaneously providing good implantability.

PMID- 15163980
TI  - [A case of successful one-stage correction of abdominal aortic aneurysm and
      stenosis of the internal carotid artery in a 78-year-old patient].
AB  - Presented herein are the results of successful one-stage revascularization of the
      brain and reconstruction of the abdominal aorta in a 78-year old patient with
      infrarenal abdominal aortic aneurysm, the signs of rupture, stenosis of the left
      renal artery and multiple aortic arch lesions -- stenoses of both internal
      carotid arteries and both vertebral arteries. The sequence and technology of
      surgical intervention are described.

PMID- 15163981
TI  - [The simultaneous operation for rectal cancer and abdominal aortic aneurysm].
AB  - The authors present a successful case of simultaneous operation for rectal cancer
      and abdominal aortic aneurysm.

PMID- 15163982
TI  - Assessment of the patient's quality of life in the long-term postoperative period
      after reconstructions on lower extremity arteries.
AB  - The study accrued 28 male patients provided reconstruction for atherosclerotic
      lesion of lower extremity arteries. Their ages ranged from 36 to 69 years, with a
      mean of 57.73+/-8.75 years. Degree IIB ischemia according to the R. Fontaine
      classification modified by A. V. Pokrovsky was present in 10, degree III in 17
      patients, and degree IV in one patient. The level end degree of lesion were
      assessed using contrast angiography and Doppler ultrasound. Before and after
      operation all the patients underwent measurements of the painless walking
      distance and regional systolic pressure on the shoulder and ankle as well as of
      the ankle/brachial pressure index. The quality of life was evaluated in all the
      patients with the aid of a MOS SF36 questionnaire before and 3 months after
      operation. The individual and typological personality properties were defined by
      the psychodiagnostic test (PDT). Operation was followed by a significant rise of
      the pressure index, painless walking index, and an improvement of the patient's
      quality of life according to the scales "physical function" and "physical pain".
      The correlation was established between the painless walking distance and
      indicators of the "physical function" scale (r=0.48, p<0.05) and "physical pain "
      (r=0.44, p>0.05) as well as between the ankle/brachial pressure index and general
      health status (r=0.58, p<0.02). The relationship was revealed between the change
      in the patient's quality of life after operation and individual-typological
      personality properties. The correlation coefficient between the scales of
      "neurotism" according to the PDT: and "physical function", "physical role" and
      "emotional role" according to the SF36 constituted -0.47, -0.54 and - -0.49
      respectively (p<0.05) that between psychotism and the general health status was 
      0.49 (p<0.05), and that between mental instability and physical and emotional
      role -0.66 and -0,61 respectively (p<0.01).

PMID- 15163983
TI  - [Critical ischemia resulted from inadequate outpatient management of lower limb
      chronic arterial obliterations].
AB  - Management of critical and subcritical lower limb ischemia poses a challenge due
      to poor effectiveness and high costs of therapy. Problem solving supposes not
      only the development of effective surgical and medical management of severe
      arterial insufficiency, but also preventive efforts on early outpatient stage.
      The paper reviews 611 patients with lower limb arterial obliterative lesions and
      correlates age, sex, concomitant diseases, stage of arterial insufficiency and
      risk factors. Consideration of these parameters can be useful in choosing the
      most effective management strategy. Authors mention that in community outpatient
      facilities treatment effectiveness of chronic lower limb arterial obliterative
      lesions does not exceed 40%, white the success of conservative treatment
      according to the protocol developed in their clinics reaches 90%. It means that
      there is a real perspective of lowering the incidence of severe lower limb
      arterial insufficiency managed in hospital environment by improving preventive
      and therapeutic strategies at outpatient care level.

PMID- 15163984
TI  - [Aspirin versus oral anticoagulants following lower limb arterial
      reconstructions: what to choose?].
AB  - Graft thrombosis in long-term postoperative period after lower extremity arterial
      reconstructions often results in limb loss. In some studies prolonged
      antithrombotic therapy was demonstrated to improve long-term patency of vascular
      grafts. Nevertheless little consensus exists on the optimal antithrombotic
      agents. The paper reviews publications on the problem. Oral anticoagulants seem
      to be feasible for reconstructions with poor outflow. In such cases strict
      laboratory monitoring of blood coagulation system is mandatory to prevent
      hemorrhagic complications.

PMID- 15163985
TI  - Evaluation of the efficacy of heparins of varying molecular mass and duration of
      their use in the treatment of patients with acute venous thrombosis.
AB  - This paper analyses the results of examination and treatment of 90 patients with
      acute thrombosis in the inferior vena cava system. To verify the diagnosis, use
      was made of contrast phlebography (retrograde iliocavography), ultrasound
      angioscanning, and perfusion scanning of the lungs, The treatment was carried out
      using heparins of varying molecular mass given for a short and longer time
      together with indirect anticoagulants. It has been demonstrated that the use of
      low-molecular heparin does not produce any noticeable changes in the hemostatic
      system, which can be revealed by standard coagulation tests. In the authors
      opinion, a differentiated approach is required to the choice of the regimes of
      heparin therapy. The indications for the use of heparins have been worked out.
      Early administration of vitamin K raises the efficacy of anticoagulant therapy
      and shortens the time of heparin therapy. The use of low-molecular heparin allows
      to minimize the incidence of thromboembolic and hemorrhagic events without an
      increase in the total expenses for treatment.

PMID- 15163986
TI  - [Size of viable myocardium and collateral blood flow in patients with coronary
      artery occlusion].
AB  - The aim of the study was to investigate correlation between collateral blood flow
      to occluded coronary vessel and the size of viable myocardium in the area fed by
      that artery. Total 295 patients with coronary artery occlusion were divided into
      2 groups. The 1st group included 193 patients with the history of Q-wave
      myocardial infarction (MI), the 2nd group - 102 patients with non-Q-wave MI or
      without MI. Left ventriculography evidenced lesser volume of viable myocardium in
      the 1st group compared with the 2nd. All patients were assessed for collateral
      blood flow (CBF) to occluded vessel. There was significantly higher incidence of
      minor (grade I) or absent (grade 0) CBF in the 1st group - 71 (36.9%) and 10
      (5.1%) cases, respectively - compared with the 2nd group - 15 (14.7%) and 0 (0%)
      cases, respectively (p<0.05). Unlike this, satisfactory (grade II) and good
      (grade III) CBF to distal segments of occluded artery was more frequent in the
      2nd group - 71 (69.6%) and 16 (15.7%) cases, respectively, compared with the 1st
      group - 102 (52.9%) and 10 (5.1%) cases, respectively (p<0.05). The authors
      conclude that evaluation of CBF level can complement the assessment of viable
      myocardium in the occluded coronary artery area, and the presence of the II-III
      grade CBF can support the necessity of occluded vessel angioplasty.

PMID- 15163987
TI  - Scintigraphic evaluation of myocardial and cerebral blood flow in patients with a
      history of coronary artery bypass grafting.
AB  - This paper deals with a comparative scintigraphic evaluation of the changes that
      occur in coronary and cerebral circulation in patients with coronary artery
      disease (CAD) after coronary artery bypass grafting (CABG) under conditions of
      cardiopulmonary bypass (CPB) or beating heart. Twenty-nine CAD patients who
      underwent CPB were examined. Of these, 14 patients were operated on using CPB
      (the first group) and 15 patients on the beating heart using the myocardial
      "stabilizer" Octopus (the 2nd group). The patient groups matched in terms of the
      age, sex, the clinical and angiographic factors. Perfusion scintigraphy of the
      heart and brain by means of single-photon emission computed tomography (SPECT)
      and the neurologic evaluation were performed twice in all the patients: before
      and 2-4 weeks after CABG. The second group patients demonstrated a significant
      lowering of the mean magnitude of stable defects (SD) of myocardial perfusion.
      The lowering or disappearance of SD was observed in a greater percentage of cases
      versus the first group. All the patients were found to have areas of hypokinesis
      in the SD projection. Also, the second group showed a significant rise of the
      mean magnitude of left ventricle ejection fraction. Operations with CPB were
      associated with a 5% decrease of cerebral blood flow in the frontal and temporal
      lobes of the right hemisphere. No significant deterioration of brain perfusion
      was observed in patients (on the whole in the group) operated on without heart
      arrest. It is noteworthy that there was a significant improvement of the average
      group indicators of cerebral perfusion in the right occipital and posterior
      segments of the temporal lobes. The changes in cerebral perfusion were in
      agreement with the course of changes in the cognitive status. Thus, CABG on the
      resting heart in CAD patients favours a more remarkable restoration of perfusion
      and contractility of the hibernated myocardium versus revascularization performed
      under CPB and exerts, as a result, a beneficial effect on cerebral circulation
      and the neuropsychological status of the patients.

PMID- 15163988
TI  - [Homocysteine: why is it harmful?].
AB  - This paper discusses the potential pathogenetic mechanisms by which the damaging
      action of hyperhomocysteinemia on the vessels is realized, namely a negative
      effect on the structure and function of the vessel wall, on proliferation of
      smooth muscle cells and endothelium-dependent vasodilatation; on the processes of
      blood cell interaction with the vessel wall (adhesion of monocytes, platelet
      adhesion and aggregation, etc): prothrombogenic action on the coagulation system,
      and effect of homocysteine on adenosine concentration in plasma and tissues.

PMID- 15163989
TI  - [Original nitinol monowire stent for percutaneous iliac arterial
      reconstructions].
AB  - Nitinol monowire stents of original construction were implanted to 35 patients
      (aged from 36 to 84, mean 53.9) with atherosclerotic lesions of iliac arteries.
      Arterial stenosis ranged from 50% to 100% (mean 72.2%), ankle-brachial index
      (ABI) averaged 0.45+/-0.12. Initial success was achieved in 97.1% of procedures.
      Ultrasonography 3 days since the procedure showed the increase of ABI up to
      0.78+/-0.16. Restenoses in the stented site was revealed during follow-up period
      (mean 24.3+/-18.3 months) in 3 patients (8.3%). In conclusion, new stent appeared
      to be effective tool for treatment of iliac atherosclerotic lesions. However long
      term restenoses resulting from intimal hyperplasia can require repetitive
      revascularization.

PMID- 15163990
TI  - [Potential of tomographic methods of diagnosis and three-dimensional analysis of
      abdominal aortic aneurysm images].
AB  - Between 1998 and 2002, 256 tomographic investigations of the abdominal aorta were
      performed. Aortic aneurysms were identified in 29 (11.3%) patients. Computed
      tomographic angiography (CTA) was provided to 16 patients 4 patients were
      examined by an electron-radiation tomograph, 6 by a spiral tomograph, 6 by a
      multispiral tomograph, and 13 patients underwent magnetic resonance angiography
      (MRA), with contrast enforcement. Two- and three-dimensional reconstructions of
      CT- and MR-angiograms were accomplished using special computerized working
      stations. Good quality MR- or CT- angiograms were obtained in all the patients
      examined. Interpretation of the angiograms did not cause noticeable difficulties.
      None of the patients required conventional contrast angiography. The
      investigations have demonstrated the benefits of multispiral CTA recognized as
      the method of choice for the diagnosis of aortic aneurysms. Of the 29 patients
      with the verified diagnosis of aneurysm of the abdominal aorta, aneurysms in 26
      subjects were located in the infrarenal aorta. Of these, 5 patients were
      identified to have an aneurysm extending to the iliac arteries. In two patients,
      aneurysms extended to the renal arteries or to the suprarenal segment. A
      thoracoabdominal aneurysm (type III) was revealed in one patient. Associated
      aneurysm and occlusive lesions of lower extremity arteries (iliac, femoral) were
      present in 15 (51.7%) cases. In the majority of cases (89.7%), aneurysms ran an
      uncomplicated course. The complications encountered by us consisted in incomplete
      (intramural) rupture (2 patients) and dissection (one patient). 22 patients were
      operated on. Comparison of the intraoperative revision data with the results of
      preoperative CT and MR angiography has established that the sensitivity of the
      tomographic methods for the diagnosis of aneurysms was 95.7% and specificity 99%.
      With an accuracy of up to 2-3 mm there were determined the size of aneurysms, the
      distance to the renal arteries, the diameter of the proximal and distal "neck",
      the extension of aneurysms to the iliac arteries, the presence of occlusive
      lesions of lower extremity arteries. CT and MR angiography with bolus contrast
      enforcement are safe and noninvasive methods for the diagnosis of aortic
      aneurysms. They have the high information content and thus allow to plan surgical
      (and possibly endovascular) interventions without the use of conventional
      contrast angiography.

PMID- 15163992
TI  - [The status of carotid arteries and the main vascular risk factors in cerebral
      infarctions of "anterior circulation"].
AB  - The aim of the work was to examine the degree of carotid stenosis, the structure
      of atherosclerotic plaques, and the predominance of the main vascular risk
      factors in patients with multiple lacunar and comparatively large "non-lacunar"
      cerebral infarctions. A study WAS made of the data on 110 patients (mean age 62.5
      years) with multiple cerebral infarctions revealed by MRT and with stenoses of
      the internal carotid artery (ICA) of varying degrees of severity. Minor lacunar
      infarctions (LI) were present in 62 cases whereas comparatively large "non
      lacunar" infarctions (NLI) in 48 cases. All the patients underwent standard
      neurologic examination, laboratory analyses, MRT of the brain with angiography
      (MRA) of the extra-intrecrania1 vessels, transcranial Doppler (TCD), and
      examination of the heart for revealing the cardioembolic nature of cerebral
      infarctions. Among patients with both LI and NLI, arterial hypertension was the
      most frequently occurring risk factor in 53 (85%) and 35 (73%) patients
      respectively. In the study groups, there were no appreciable differences in the
      incidence of high hematocrit, hyperfibrinogenemia, tobacco-smoking, and diabetes
      mellitus. Patients with NLI demonstrated hypercholesterolemia, CAD and
      atherosclerosis of the peripheral vessels significantly more often (p<0.05). In
      the patient group with NLI, hemodynamically significant stenoses of the ICA were
      predominant: in 18 (37.5%) patients, they were moderate, in 12 (25%) critical,
      and 7 (14.6%) patients had occlusions whereas in LI, the portion of critical
      stenoses and ICA occlusions was cooperatively low - in 11 (17.7%) and in 5 (8.1%)
      patients respectively. Both groups showed the thickening of the complex of the
      medial CCA layer. Ultrasonopraphy of the vessels has revealed that in patients
      with NLI and LI, there predominated potentially embologenic plaques, namely in
      69% and in 53% of cases, respectively. Our investigations allow to assume that
      arterial hypertension is the most frequently occurring risk factor of cerebral
      infarction (both minor lacunar and large "non-lacunar"). Factors such as CAD,
      hypercholesterolemia, DM, hemorheological disorders, end tobacco-smoking are
      likely to have an unfavorable impact on both general and cerebral hemodynamics as
      well as on the microcirculatory bed whereby being on the whole important risk
      factors of cerebral infarction. Hemodynamically significant stenoses, especially
      critical ones, occlusions, and embologenic plaques of the ICA are
      pathogenetically closely linked with the development of "non-lacunar" cerebral
      infarctions. At the same time they, under certain conditions, may become the
      cause of multiple lacunar cerebral infarctions.

PMID- 15163991
TI  - Laser Doppler flowmetry assessment of microcirculation in upper extremities
      before and in long-term period after harvesting of radial artery.
AB  - Radial artery (RA) is rather commonly used as a graft for autoarterial myocardial
      revascularization. Consequences of RA harvesting for the development of ischemic
      disturbances in distal hand segments are poorly understood. The paper presents
      assessment of hand microcirculation (HMC) before and in late postoperative period
      after RA harvesting with modern precise diagnostic method - laser Doppler
      flowmetry (LDF). LDF assessment of HMC was carried out in 80 patients with
      ischemic heart disease (160 hands) to evaluate the possibility of RA harvesting
      for coronary artery bypass surgery. HMC classification was developed on the base
      of these measurements: type 1 -normocirculatory HMC: 6.7-17 ml/min/100 g (58%);
      type 2 - vasospastic HMC: < or = 6.7 ml/min/100 g (20%); type 3 - hyperemic HMC:
      > or = 17 ml/min/100 g (22%). In 34% of cases preoperative examination revealed
      microcirculatory asymmetry between right and left hands. Based on preoperative
      examination results in 22.9% of cases the decision was made to refuse from RA
      excision because of positive collateral circulation test developed in our
      Institute (positive decision about Patent award according to appeal
      No2000122582/14 (023905) from 28.08.2000). In 14 patients (14 upper extremities)
      HMC was measured before and 1-1.5 years after RA harvesting. After RA excision
      baseline HMC in operated hand reduced significantly while maximal HMC reserve
      remained at the level close to preoperative one. Postoperative HNMC alterations
      evidence of adequate preoperative assessment of hand collateral circulation
      potential. In case of blood flow asymmetry RA must be taken from the hand with
      higher blood supply and adequate collateral microcirculation.

PMID- 15163993
TI  - Chronic diseases of lower extremity veins in industrial workers of Moscow
      (results of the epidemiological survey).
AB  - This paper describes the results of the study into the prevalence of chronic
      venous diseases among industrial workers of Moscow. It has been established that
      chronic venous diseases are fairly prevalent among industrial workers. They
      affect the people of both sexes (67.5% of women and 50.4% of men), varying age
      and occupation. With age their incidence rises. The most significant risk factors
      of the onset of chronic venous diseases include hereditary predisposition,
      pregnancy and birth, overweight, and intake of hormonal contraceptives. The study
      has demonstrated that in most cases, such patients are not rendered medical
      assistance.

PMID- 15163994
TI  - [Comparison of variceal surgery methods].
AB  - Combined ablation of great saphenous vein (GSV) remains the most common way of
      lower limb variceal management. In recent years different surgical methods were
      proposed for the treatment of varices. Nevertheless, their invasiveness, poor
      esthetic outcome, prolonged postoperative rehabilitation and recurrences cail for
      the development of new minimally invasive and highly effective methods. In the
      last 5 years a new procedure of intraoperative trunk catheter scieroobliteration
      of GSV and its tributaries was introduced. From 1997 to 2002 total 493 surgical
      corrections of lower limb varices were fulfilled, among them 374 patients were
      operated for primary variceal vein dilatations including 188 standard combined
      venectomies (1st group) and 186 trunk obliterations (2nd group). Groups were
      similar in age, sex and lesion extension. Outcomes were followed up to 4 weeks -
      5 years. Outcomes comparison between groups has demonstrated significantly lower
      incidence of postoperative subcutaneous hematomas in the 2nd group, absence of
      saphenous nerve injuries, better esthetics in the absence of additional incisions
      (remaining variceal tributaries were sclerosed postoperatively by puncture
      scieroobliteration). Besides postoperative rehabilitation period was double
      shorter in ihe 2nd group then in the 1st one. Recurrence rate in long-term period
      was similar in both groups. Thus intraoperative trunk scieroobliteration of GSV
      can be a valuable alternative for standard combined venectomy.

PMID- 15163995
TI  - Endovasal laser obliteration of the greater saphenous vein in patients with
      varicosis.
AB  - This paper describes the first results of endovasal laser obliteration of the
      greater sephenous vein in two patient groups (n=40) math varicosis. In 15 cases
      (control group), laser obliteration was employed during routine operation as an
      alternative to phlebectomy according to Babcock following crossectomy. In 25
      patients (the main group), operation was performed without ligation of the
      saphenofemoral anastomosis. After puncture and catheterization according to
      Seldinger the greater saphenous vein was exposed to thermal action over the
      length from the osteal valve to the upper third of the leg. The follow up of the
      patients amounted to 12 months. The results obtained in the main patient group
      seem most interesting. Stable elimination of truncal varicosis could be attained
      in more than 90% of cases, which was associated with quick medicosocial
      rehabilitation, the minimal number of complications and an excellent cosmetic
      effect.

PMID- 15163996
TI  - [Sclerotherapy of small pelvis varicosis].
AB  - This paper analyses the results of sclerotherapy provided to 89 patients with
      small pelvis varicosis. Selection of the treatment technology depended on the
      clinical variant of disease. In patients with damage to the parietal venous
      system of the pelvis, the treatment was realized by multiple repeat injections of
      a sclerosing agent to the pelvic veins in a minimal dose which may induce only
      proliferative processes in varicose vein walls. Elastic compression was not
      applied. Women with the syndrome of blood overfilling of the pelvic organs
      (visceral pattern of lesion) were provided sclerotherapy of the left ovarian vein
      followed by its pharmacological spasm. The treatment results were evaluated by
      clinical examination of patients, duplex scanning end estimation of the quality
      of life based on the patients' self-estimation according to the recommendations
      of the International Association of Phlebologists. Excellent results were
      obtained in 32.6%, good in 46.1%, satisfactory in 19.1% and unsatisfactory
      results in 2.2% of patients.

PMID- 15163997
TI  - [Experience with the use of autoarterial conduits in coronary surgery].
AB  - Between September 1999 and until the present time 14 direct myocardial
      revascularization using arterial conduits were performed at the Department of
      Vascular Surgery and Surgical Treatment of CAD, V. Vakhidov Scientific Center of
      Surgery, RU Ministry of Public Health. The internal mammary artery was used in
      all the cases, right gastroomental artery in 2 cases. Revascularization of one
      coronary artery was accomplished in 2 patients, of two arteries in 8 and of three
      coronary arteries in 4 patients. In 12 cases, direct myocardial revascularization
      was realized on the working heart and in 2 cases, under cardiopulmonary bypass.
      Ischemic changes on the ECG at rest, recorded in the preoperative period,
      disappeared following operation. In all the patients, myocardial contractility
      (EF) after operation rose by 6-8% on an average as compared to the initial level.
      Physical exercise tolerance was measured by BEM in 6 (42.9%) patients. Angina of
      effort, FC II, was diagnosed only in 2 patients. All the patients were discharged
      in a satisfactory condition. Only patients with unstable angina were recommended
      to take long-acting nitrates whereas the remaining subjects were advised to take
      the antiaggregation doses of aspirin.

PMID- 15163998
TI  - [Relationship between the results of the treatment of patients with cerebral
      artery atherosclerosis and technology of carotid endarterectomy].
AB  - Presented herein is an analysis of surgical treatment of 232 patients with
      atherosclerotic stenoses and occlusions of the carotid arteries, including 144
      persons with bilateral lesions. The patients underwent carotid endarterectomy
      according to the traditional and eversion techniques. Analysis of the short- and
      long-term results has demonstrated that they do not depend on the technique of
      endarterectomy. The risk of carotid endarterectomy rises in occlusions of the
      contralateral internal carotid artery. The measures for this risk minimization
      are offered. The long-term results of surgical treatment of asymptomatic stenoses
      are better as compared to the results of drug therapy. Surgical treatment of
      atherosclerotic lesions followed by the treatment of lipid metabolism disorders
      provides for the improvement of the quality of life due to the restoration of
      work fitness, physical and social activity.

PMID- 15163999
TI  - [Effect of aortic clamping on hemodynamics at reconstruction of the
      thoracoabdominal aorta].
AB  - This paper describes an experience with monitoring and computerized follow up of
      the hemodynamic status in 60 patients at and right after reconstruction of the
      thoracoabdominal aorta. In addition to the routine control, measurements were
      made of the pressure in the large vessels and cavities of the heart, duration of
      each heart contraction and CI. The following parameters were computed
      automatically: the status of the ventricles for each heart contraction,
      resistance of the greater end pulmonary circulation, elasticity of the arterial,
      venous, pulmonary arterial and pulmonary venous reservoirs, also for each cardiac
      cycle. At the generally accepted monitoring the hemodynamic responses to the
      surgeon's manipulations on the aorta appear smoothed or are not visualized at
      all. The control of each heart contraction reveals the responses to application
      of the clamp and its removal from the aorta, with their hemodynamic significance
      being not questionable. Aortic clamping and clamp removal from the aorta are
      associated with the generalized response of the regulatory systems of the body.
      The slow and thoroughly controlled aortic clamping and graded, controlled blood
      flow restoration due to clamp removal as well as the use of sodium nitroprusside
      (trimetafan or isofluran are preferable) allow to avoid an abrupt stroke load of
      the left ventricle of the heart and, respectively, the generalized response of
      the regulatory systems of the body.

PMID- 15164000
TI  - Another piece in the BRCA1 puzzle.

PMID- 15164002
TI  - Biochemistry matters.

PMID- 15164003
TI  - Helicases become mechanistically simpler and functionally more complex.

PMID- 15164004
TI  - A new role for an old cofactor.

PMID- 15164005
TI  - Opening the gate in potassium channels.

PMID- 15164008
TI  - The mRNA cap-binding protein eIF4E in post-transcriptional gene expression.
AB  - Eukaryotic initiation factor 4E (eIF4E) has central roles in the control of
      several aspects of post-transcriptional gene expression and thereby affects
      developmental processes. It is also implicated in human diseases. This review
      explores the relationship between structural, biochemical and biophysical aspects
      of eIF4E and its function in vivo, including both long-established roles in
      translation and newly emerging ones in nuclear export and mRNA decay pathways.

PMID- 15164009
TI  - Science appeal.

PMID- 15164010
TI  - Nondeletional pathways for the development of autoreactive thymocytes.

PMID- 15164011
TI  - Balancing life and death.

PMID- 15164012
TI  - V(D)J recombinational accessibility-heading in the opposite direction?

PMID- 15164013
TI  - Cutting into innate immunity.

PMID- 15164014
TI  - Dendritic cells: the immune information management experts.

PMID- 15164016
TI  - Getting a grip on things: how do communities of bacterial symbionts become
      established in our intestine?
AB  - The gut contains our largest collection of resident microorganisms. One obvious
      question is how microbial communities establish and maintain themselves within a
      perfused intestine. The answers, which may come in part from observations made by
      environmental engineers and glycobiologists, have important implications for
      immunologists who wish to understand how indigenous microbial communities are
      accommodated. Here we propose that the mucus gel layer overlying the intestinal
      epithelium is a key contributor to the structural and functional stability of
      this microbiota and its tolerance by the host.

PMID- 15164020
TI  - The rise of cafe culture.

PMID- 15164021
TI  - Dragged into the fray.

PMID- 15164017
TI  - Elaborate interactions between the immune and nervous systems.
AB  - The immune system and the nervous system maintain extensive communication,
      including 'hardwiring' of sympathetic and parasympathetic nerves to lymphoid
      organs. Neurotransmitters such as acetylcholine, norepinephrine, vasoactive
      intestinal peptide, substance P and histamine modulate immune activity.
      Neuroendocrine hormones such as corticotropin-releasing factor, leptin and alpha
      melanocyte stimulating hormone regulate cytokine balance. The immune system
      modulates brain activity, including body temperature, sleep and feeding behavior.
      Molecules such as the major histocompatibility complex not only direct T cells to
      immunogenic molecules held in its cleft but also modulate development of neuronal
      connections. Neurobiologists and immunologists are exploring common ideas like
      the synapse to understand properties such as memory that are shared in these two
      systems.

PMID- 15164023
TI  - Project structure blamed for Beagle 2 loss.

PMID- 15164022
TI  - Clinicians win fight to overturn patent for breast-cancer gene.

PMID- 15164024
TI  - Monsanto wins seven-year court battle for seed patent.

PMID- 15164025
TI  - Tissue survey raises spectre of 'second wave' of vCJD.

PMID- 15164026
TI  - Biodefence project accused of violating weapons treaty.

PMID- 15164027
TI  - Japan announces follow-up to human genome project.

PMID- 15164028
TI  - Microbiology gaining ground after lean years.

PMID- 15164029
TI  - Pop science pulls in public as cafe culture goes global.

PMID- 15164030
TI  - Britain opens first repository to speed work on stem cells.

PMID- 15164031
TI  - AIDS-vaccine firm needled by stock-exchange rules.

PMID- 15164032
TI  - Striking back.

PMID- 15164033
TI  - NASA meets Hollywood: catch a falling star.

PMID- 15164034
TI  - Efforts to help Africa are tripped up by red tape.

PMID- 15164035
TI  - Call for action to protect free exchange of ideas.

PMID- 15164041
TI  - A late change to the programme.

PMID- 15164042
TI  - Automata make antisense.

PMID- 15164043
TI  - Granular materials: the Brazil nut effect--in reverse.

PMID- 15164045
TI  - Genome sequencing: differences with the relatives.

PMID- 15164046
TI  - Earth science: just add more water.

PMID- 15164047
TI  - Organic chemistry: OOO!

PMID- 15164048
TI  - Ageing: mice and mitochondria.

PMID- 15164049
TI  - Geochemistry: warm debate on early climate.

PMID- 15164051
TI  - Pigment chemistry: the red sweat of the hippopotamus.
AB  - Within a few minutes of perspiration, the colourless, viscous sweat of the
      hippopotamus gradually turns red, and then brown as the pigment polymerizes. Here
      we isolate and characterize the pigments responsible for this colour reaction.
      The unstable red and orange pigments turn out to be non-benzenoid aromatic
      compounds that are unexpectedly acidic and have antibiotic as well as sunscreen
      activity.

PMID- 15164052
TI  - Quality assessment of the human genome sequence.
AB  - As the final sequencing of the human genome has now been completed, we present
      the results of the largest examination of the quality of the finished DNA
      sequence. The completed study covers the major contributing sequencing centres
      and is based on a rigorous combination of laboratory experiments and
      computational analysis.

PMID- 15164056
TI  - Electron-hole symmetry in a semiconducting carbon nanotube quantum dot.
AB  - Optical and electronic phenomena in solids arise from the behaviour of electrons
      and holes (unoccupied states in a filled electron sea). Electron-hole symmetry
      can often be invoked as a simplifying description, which states that electrons
      with energy above the Fermi sea behave the same as holes below the Fermi energy.
      In semiconductors, however, electron-hole symmetry is generally absent, because
      the energy-band structure of the conduction band differs from the valence band.
      Here we report on measurements of the discrete, quantized-energy spectrum of
      electrons and holes in a semiconducting carbon nanotube. By applying a voltage to
      a gate electrode, an individual nanotube is filled controllably with a precise
      number of either electrons or holes, starting from one. The discrete excitation
      spectrum for a nanotube with N holes is strikingly similar to the corresponding
      spectrum for N electrons. This observation of near-perfect electron-hole symmetry
      demonstrates that a semiconducting nanotube can be free of charged impurities,
      even in the limit of few electrons or holes. We furthermore find an anomalously
      small Zeeman spin splitting and an excitation spectrum indicating strong electron
      electron interactions.

PMID- 15164055
TI  - DNA sequence and comparative analysis of chimpanzee chromosome 22.
AB  - Human-chimpanzee comparative genome research is essential for narrowing down
      genetic changes involved in the acquisition of unique human features, such as
      highly developed cognitive functions, bipedalism or the use of complex language.
      Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee
      chromosome 22. By comparing the whole sequence with the human counterpart,
      chromosome 21, we found that 1.44% of the chromosome consists of single-base
      substitutions in addition to nearly 68,000 insertions or deletions. These
      differences are sufficient to generate changes in most of the proteins. Indeed,
      83% of the 231 coding sequences, including functionally important genes, show
      differences at the amino acid sequence level. Furthermore, we demonstrate
      different expansion of particular subfamilies of retrotransposons between the
      lineages, suggesting different impacts of retrotranspositions on human and
      chimpanzee evolution. The genomic changes after speciation and their biological
      consequences seem more complex than originally hypothesized.

PMID- 15164057
TI  - Electric polarization reversal and memory in a multiferroic material induced by
      magnetic fields.
AB  - Ferroelectric and magnetic materials are a time-honoured subject of study and
      have led to some of the most important technological advances to date. Magnetism
      and ferroelectricity are involved with local spins and off-centre structural
      distortions, respectively. These two seemingly unrelated phenomena can coexist in
      certain unusual materials, termed multiferroics. Despite the possible coexistence
      of ferroelectricity and magnetism, a pronounced interplay between these
      properties has rarely been observed. This has prevented the realization of
      multiferroic devices offering such functionality. Here, we report a striking
      interplay between ferroelectricity and magnetism in the multiferroic TbMn2O5,
      demonstrated by a highly reproducible electric polarization reversal and
      permanent polarization imprint that are both actuated by an applied magnetic
      field. Our results point to new device applications such as magnetically recorded
      ferroelectric memory.

PMID- 15164054
TI  - The DNA sequence and comparative analysis of human chromosome 10.
AB  - The finished sequence of human chromosome 10 comprises a total of 131,666,441
      base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase
      of heterochromatic sequence within the pericentromeric region of the short and
      long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which
      816 are protein coding, and 430 are pseudogenes. We observed widespread
      occurrence of overlapping coding genes (either strand) and identified 67
      antisense transcripts. Our analysis suggests that both inter- and
      intrachromosomal segmental duplications have impacted on the gene count on
      chromosome 10. Multispecies comparative analysis indicated that we can readily
      annotate the protein-coding genes with current resources. We estimate that over
      95% of all coding exons were identified in this study. Assessment of single base
      changes between the human chromosome 10 and chimpanzee sequence revealed nonsense
      mutations in only 21 coding genes with respect to the human sequence.

PMID- 15164053
TI  - DNA sequence and analysis of human chromosome 9.
AB  - Chromosome 9 is highly structurally polymorphic. It contains the largest
      autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans,
      whereas pericentric inversions occur in more than 1% of the population. The
      finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs
      and represents >99.6% of the region. Analysis of the sequence reveals many intra-
      and interchromosomal duplications, including segmental duplications adjacent to
      both the centromere and the large heterochromatic block. We have annotated 1,149
      genes, including genes implicated in male-to-female sex reversal, cancer and
      neurodegenerative disease, and 426 pseudogenes. The chromosome contains the
      largest interferon gene cluster in the human genome. There is also a region of
      exceptionally high gene and G + C content including genes paralogous to those in
      the major histocompatibility complex. We have also detected recently duplicated
      genes that exhibit different rates of sequence divergence, presumably reflecting
      natural selection.

PMID- 15164058
TI  - Evidence from massive siderite beds for a CO2-rich atmosphere before
      approximately 1.8 billion years ago.
AB  - It is generally thought that, in order to compensate for lower solar flux and
      maintain liquid oceans on the early Earth, methane must have been an important
      greenhouse gas before approximately 2.2 billion years (Gyr) ago. This is based
      upon a simple thermodynamic calculation that relates the absence of siderite
      (FeCO3) in some pre-2.2-Gyr palaeosols to atmospheric CO2 concentrations that
      would have been too low to have provided the necessary greenhouse effect. Using
      multi-dimensional thermodynamic analyses and geological evidence, we show here
      that the absence of siderite in palaeosols does not constrain atmospheric CO2
      concentrations. Siderite is absent in many palaeosols (both pre- and post-2.2-Gyr
      in age) because the O2 concentrations and pH conditions in well-aerated soils
      have favoured the formation of ferric (Fe3+)-rich minerals, such as goethite,
      rather than siderite. Siderite, however, has formed throughout geological history
      in subsurface environments, such as euxinic seas, where anaerobic organisms
      created H2-rich conditions. The abundance of large, massive siderite-rich beds in
      pre-1.8-Gyr sedimentary sequences and their carbon isotope ratios indicate that
      the atmospheric CO2 concentration was more than 100 times greater than today,
      causing the rain and ocean waters to be more acidic than today. We therefore
      conclude that CO2 alone (without a significant contribution from methane) could
      have provided the necessary greenhouse effect to maintain liquid oceans on the
      early Earth.

PMID- 15164059
TI  - Low electrical resistivity associated with plunging of the Nazca flat slab
      beneath Argentina.
AB  - Beneath much of the Andes, oceanic lithosphere descends eastward into the mantle
      at an angle of about 30 degrees (ref. 1). A partially molten region is thought to
      form in a wedge between this descending slab and the overlying continental
      lithosphere as volatiles given off by the slab lower the melting temperature of
      mantle material. This wedge is the ultimate source for magma erupted at the
      active volcanoes that characterize the Andean margin. But between 28 degrees and
      33 degrees S the subducted Nazca plate appears to be anomalously buoyant, as it
      levels out at about 100 km depth and extends nearly horizontally under the
      continent. Above this 'flat slab', volcanic activity in the main Andean
      Cordillera terminated about 9 million years ago as the flattening slab presumably
      squeezed out the mantle wedge. But it is unknown where slab volatiles go once
      this happens, and why the flat slab finally rolls over to descend steeply into
      the mantle 600 km further eastward. Here we present results from a
      magnetotelluric profile in central Argentina, from which we infer enhanced
      electrical conductivity along the eastern side of the plunging slab, indicative
      of the presence of partial melt. This conductivity structure may imply that
      partial melting occurs to at least 250 km and perhaps to more than 400 km depth,
      or that melt is supplied from the 410 km discontinuity, consistent with the
      transition-zone 'water-filter' model of Bercovici and Karato.

PMID- 15164060
TI  - Aldehyde suppression of copepod recruitment in blooms of a ubiquitous planktonic
      diatom.
AB  - The growth cycle in nutrient-rich, aquatic environments starts with a diatom
      bloom that ends in mass sinking of ungrazed cells and phytodetritus. The low
      grazing pressure on these blooms has been attributed to the inability of
      overwintering copepod populations to track them temporally. We tested an
      alternative explanation: that dominant diatom species impair the reproductive
      success of their grazers. We compared larval development of a common
      overwintering copepod fed on a ubiquitous, early-blooming diatom species with its
      development when fed on a typical post-bloom dinoflagellate. Development was
      arrested in all larvae in which both mothers and their larvae were fed the diatom
      diet. Mortality remained high even if larvae were switched to the dinoflagellate
      diet. Aldehydes, cleaved from a fatty acid precursor by enzymes activated within
      seconds after crushing of the cell, elicit the teratogenic effect. This insidious
      mechanism, which does not deter the herbivore from feeding but impairs its
      recruitment, will restrain the cohort size of the next generation of early-rising
      overwinterers. Such a transgenerational plant-herbivore interaction could explain
      the recurringly inefficient use of a predictable, potentially valuable food
      resource--the spring diatom bloom--by marine zooplankton.

PMID- 15164061
TI  - Predator diversity dampens trophic cascades.
AB  - Food web complexity is thought to weaken the strength of terrestrial trophic
      cascades in which strong impacts of natural enemies on herbivores cascade to
      influence primary production indirectly. Predator diversity can enhance food web
      complexity because predators may feed on each other and on shared prey. In such
      cases, theory suggests that the impact of predation on herbivores relaxes and
      cascading effects on basal resources are dampened. Despite this view, no
      empirical studies have explicitly investigated the role of predator diversity in
      mediating primary productivity in a natural terrestrial system. Here we compare,
      in a coastal marsh community, impacts of arthropod predators on herbivores and
      plant productivity between a simple food web with a single predator species and a
      complex food web with a diverse predator assemblage. We show that enhancing
      predator diversity dampens enemy effects on herbivores and weakens trophic
      cascades. Consequently, changes in diversity at higher trophic levels can
      significantly alter ecosystem function in natural systems.

PMID- 15164062
TI  - Object-based attention determines dominance in binocular rivalry.
AB  - A question of long-standing interest to philosophers, psychologists and
      neuroscientists is how the brain selects which signals enter consciousness.
      Binocular rivalry and attention both involve selection of visual stimuli, but
      affect perception quite differently. During binocular rivalry, awareness
      alternates between two different stimuli presented to the two eyes. In contrast,
      attending to one of two different stimuli impairs discrimination of the ignored
      stimulus, but without causing it to disappear from consciousness. Here we show
      that despite this difference, attention and rivalry rely on shared object-based
      selection mechanisms. We cued attention to one of two superimposed transparent
      surfaces and then deleted the image of one surface from each eye, resulting in
      rivalry. Observers usually reported seeing only the cued surface. They were also
      less accurate in judging unpredictable changes in the features of the uncued
      surface. Our design ensured that selection of the cued surface could not have
      resulted from spatial, ocular or feature-based mechanisms. Rather, attention was
      drawn to one surface, and this caused the other surface to be perceptually
      suppressed during rivalry. These results raise the question of how object
      representations compete during these two forms of perceptual selection, even as
      the features of those objects change unpredictably over time.

PMID- 15164063
TI  - VEGF delivery with retrogradely transported lentivector prolongs survival in a
      mouse ALS model.
AB  - Amyotrophic lateral sclerosis (ALS) causes adult-onset, progressive motor neuron
      degeneration in the brain and spinal cord, resulting in paralysis and death three
      to five years after onset in most patients. ALS is still incurable, in part
      because its complex aetiology remains insufficiently understood. Recent reports
      have indicated that reduced levels of vascular endothelial growth factor (VEGF),
      which is essential in angiogenesis and has also been implicated in
      neuroprotection, predispose mice and humans to ALS. However, the therapeutic
      potential of VEGF for the treatment of ALS has not previously been assessed. Here
      we report that a single injection of a VEGF-expressing lentiviral vector into
      various muscles delayed onset and slowed progression of ALS in mice engineered to
      overexpress the gene coding for the mutated G93A form of the superoxide dismutase
      1 (SOD1(G93A)) (refs 7-10), even when treatment was only initiated at the onset
      of paralysis. VEGF treatment increased the life expectancy of ALS mice by 30 per
      cent without causing toxic side effects, thereby achieving one of the most
      effective therapies reported in the field so far.

PMID- 15164064
TI  - Premature ageing in mice expressing defective mitochondrial DNA polymerase.
AB  - Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a
      variety of tissues during ageing in humans, monkeys and rodents. These mutations
      are unevenly distributed and can accumulate clonally in certain cells, causing a
      mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal
      muscle and brain. In terms of the ageing process, their possible causative
      effects have been intensely debated because of their low abundance and purely
      correlative connection with ageing. We have now addressed this question
      experimentally by creating homozygous knock-in mice that express a proof-reading
      deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA
      polymerase. Here we show that the knock-in mice develop an mtDNA mutator
      phenotype with a threefold to fivefold increase in the levels of point mutations,
      as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA
      mutations is associated with reduced lifespan and premature onset of ageing
      related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair
      loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced
      fertility and heart enlargement. Our results thus provide a causative link
      between mtDNA mutations and ageing phenotypes in mammals.

PMID- 15164066
TI  - Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand
      exchange.
AB  - Homologous recombination is crucial for the repair of DNA breaks and maintenance
      of genome stability. In Escherichia coli, homologous recombination is dependent
      on the RecA protein. In the presence of ATP, RecA mediates the homologous DNA
      pairing and strand exchange reaction that links recombining DNA molecules. DNA
      joint formation is initiated through the nucleation of RecA onto single-stranded
      DNA (ssDNA) to form helical nucleoprotein filaments. Two RecA-like recombinases,
      Rad51 and Dmc1, exist in eukaryotes. Whereas Rad51 is needed for both mitotic and
      meiotic recombination events, the function of Dmc1 is restricted to meiosis. Here
      we examine human Dmc1 protein (hDmc1) for the ability to promote DNA strand
      exchange, and show that hDmc1 mediates strand exchange between paired DNA
      substrates over at least several thousand base pairs. DNA strand exchange
      requires ATP and is strongly dependent on the heterotrimeric ssDNA-binding
      molecule replication factor A (RPA). We present evidence that hDmc1-mediated DNA
      recombination initiates through the nucleation of hDmc1 onto ssDNA to form a
      helical nucleoprotein filament. The DNA strand exchange activity of hDmc1 is
      probably indispensable for repair of DNA double-strand breaks during meiosis and
      for maintaining the ploidy of meiotic chromosomes.

PMID- 15164065
TI  - Assembly and function of a bacterial genotoxin.
AB  - The tripartite cytolethal distending toxin (CDT) induces cell cycle arrest and
      apoptosis in eukaryotic cells. The subunits CdtA and CdtC associate with the
      nuclease CdtB to form a holotoxin that translocates CdtB into the host cell,
      where it acts as a genotoxin by creating DNA lesions. Here we show that the
      crystal structure of the holotoxin from Haemophilus ducreyi reveals that CDT
      consists of an enzyme of the DNase-I family, bound to two ricin-like lectin
      domains. CdtA, CdtB and CdtC form a ternary complex with three interdependent
      molecular interfaces, characterized by globular, as well as extensive non
      globular, interactions. The lectin subunits form a deeply grooved, highly
      aromatic surface that we show to be critical for toxicity. The holotoxin
      possesses a steric block of the CdtB active site by means of a non-globular
      extension of the CdtC subunit, and we identify putative DNA binding residues in
      CdtB that are essential for toxin activity.

PMID- 15164068
TI  - Genomes for medicine.
AB  - We have the human genome sequence. It is freely available, accurate and nearly
      complete. But is the genome ready for medicine? The new resource is already
      changing genetic research strategies to find information of medical value. Now we
      need high-quality annotation of all the functionally important sequences and the
      variations within them that contribute to health and disease. To achieve this, we
      need more genome sequences, systematic experimental analyses, and extensive
      information on human phenotypes. Flexible and user-friendly access to well
      annotated genomes will create an environment for innovation, and the potential
      for unlimited use of sequencing in biomedical research and practice.

PMID- 15164069
TI  - Mapping complex disease loci in whole-genome association studies.
AB  - Identification of the genetic polymorphisms that contribute to susceptibility for
      common diseases such as type 2 diabetes and schizophrenia will aid in the
      development of diagnostics and therapeutics. Previous studies have focused on the
      technique of genetic linkage, but new technologies and experimental resources
      make whole-genome association studies more feasible. Association studies of this
      type have good prospects for dissecting the genetics of common disease, but they
      currently face a number of challenges, including problems with multiple testing
      and study design, definition of intermediate phenotypes and interaction between
      polymorphisms.

PMID- 15164070
TI  - Predicting disease using genomics.
AB  - Information from the human genome sequence will eventually alter many aspects of
      clinical practice. It will increase through our understanding of disease
      mechanisms, and guide the development of new drugs and therapeutic procedures. In
      the short term, however, knowledge of the genome will have a profound clinical
      impact on the diagnostic capability of clinical genetics laboratories. Molecular
      phenotyping using genetic and genomic information will allow early and more
      accurate prediction and diagnosis of disease and of disease progression. Medicine
      will become oriented towards disease prevention rather than efforts to cure
      people at late stages of illness.

PMID- 15164071
TI  - Epigenetics in human disease and prospects for epigenetic therapy.
AB  - Epigenetic mechanisms, which involve DNA and histone modifications, result in the
      heritable silencing of genes without a change in their coding sequence. The study
      of human disease has focused on genetic mechanisms, but disruption of the balance
      of epigenetic networks can cause several major pathologies, including cancer,
      syndromes involving chromosomal instabilities, and mental retardation. The
      development of new diagnostic tools might reveal other diseases that are caused
      by epigenetic alterations. Great potential lies in the development of 'epigenetic
      therapies'--several inhibitors of enzymes controlling epigenetic modifications,
      specifically DNA methyltransferases and histone deacetylases, have shown
      promising anti-tumorigenic effects for some malignancies.

PMID- 15164072
TI  - Moving towards individualized medicine with pharmacogenomics.
AB  - Individuals respond differently to drugs and sometimes the effects are
      unpredictable. Differences in DNA that alter the expression or function of
      proteins that are targeted by drugs can contribute significantly to variation in
      the responses of individuals. Many of the genes examined in early studies were
      linked to highly penetrant, single-gene traits, but future advances hinge on the
      more difficult challenge of elucidating multi-gene determinants of drug response.
      This intersection of genomics and medicine has the potential to yield a new set
      of molecular diagnostic tools that can be used to individualize and optimize drug
      therapy.

PMID- 15164073
TI  - Oncogenomics and the development of new cancer therapies.
AB  - Scientists have sequenced the human genome and identified most of its genes. Now
      it is time to use these genomic data, and the high-throughput technology
      developed to generate them, to tackle major health problems such as cancer. To
      accelerate our understanding of this disease and to produce targeted therapies,
      further basic mutational and functional genomic information is required. A
      systematic and coordinated approach, with the results freely available, should
      speed up progress. This will best be accomplished through an international
      academic and pharmaceutical oncogenomics initiative.

PMID- 15164074
TI  - The case for a US prospective cohort study of genes and environment.
AB  - Information from the Human Genome Project will be vital for defining the genetic
      and environmental factors that contribute to health and disease. Well-designed
      case-control studies of people with and without a particular disease are
      essential for this, but rigorous and unbiased conclusions about the causes of
      diseases and their population-wide impact will require a representative
      population to be monitored over time (a prospective cohort study). The time is
      right for the United States to consider such a project.

PMID- 15164075
TI  - Organizational challenges in clinical genomic research.
AB  - Genome sequence data are enabling clinical genomic investigation, in which the
      characteristics of human patients are explored using comprehensive inventories of
      biomolecules. Successful investigators must navigate rapid technological change,
      collect and analyse large volumes of data, and engage systems of clinical care.
      Such projects will increasingly rely on fully integrated multidisciplinary teams,
      demanding new organizational models in academic biomedical research.

PMID- 15164076
TI  - Back to life.

PMID- 15164077
TI  - Taking a risk in start-ups.

PMID- 15164079
TI  - Recruiters and industry. Rules of engagement.

PMID- 15164081
TI  - Structural basis of protein phosphatase 1 regulation.
AB  - The coordinated and reciprocal action of serine/threonine (Ser/Thr) protein
      kinases and phosphatases produces transient phosphorylation, a fundamental
      regulatory mechanism for many biological processes. The human genome encodes a
      far greater number of Ser/Thr protein kinases than of phosphatases. Protein
      phosphatase 1 (PP1), in particular, is ubiquitously distributed and regulates a
      broad range of cellular functions, including glycogen metabolism, cell-cycle
      progression and muscle relaxation. PP1 has evolved effective catalytic machinery
      but lacks substrate specificity. Substrate specificity is conferred upon PP1
      through interactions with a large number of regulatory subunits. The regulatory
      subunits are generally unrelated, but most possess the RVxF motif, a canonical
      PP1-binding sequence. Here we reveal the crystal structure at 2.7 A resolution of
      the complex between PP1 and a 34-kDa N-terminal domain of the myosin phosphatase
      targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in
      smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the
      RVxF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping
      of the catalytic cleft of PP1, contributing to the increased myosin specificity
      of this complex. The structure has general implications for the control of PP1
      activity by other regulatory subunits.

PMID- 15164082
TI  - Research in clinical psychiatry: an interdisciplinary view from Germany.

PMID- 15164085
TI  - Hormonal symphony: steroid orchestration of gene modules for sociosexual
      behaviors.
AB  - Genes induced by estrogens in the mammalian forebrain influence a variety of
      neural functions. Among them, reproductive behavior mechanisms are very well
      understood. Their functional genomics provide a theoretical paradigm for linking
      genes to neural circuits to behavior. We propose that estrogen-induced genes are
      organized in modules: Growth of hypothalamic neurons; Amplification of the
      estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex
      behavior circuitry; and Synchronization of mating behavior with ovulation. These
      modules may represent mechanistic routes for CNS management of successful
      reproduction. Moreover, new microarray results add estrogen-dependent genes,
      including some expressed in glia, suggesting possible hormone-dependent
      neuronal/glial coordination.

PMID- 15164086
TI  - Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol
      abuse and alcoholism.
AB  - Acetaldehyde, the first product of ethanol metabolism, has been speculated to be
      involved in many pharmacological and behavioral effects of ethanol. In
      particular, acetaldehyde has been suggested to contribute to alcohol abuse and
      alcoholism. In the present paper, we review current data on the role of
      acetaldehyde and ethanol metabolism in alcohol consumption and abuse. Ethanol
      metabolism involves several enzymes. Whereas alcohol dehydrogenase metabolizes
      the bulk of ethanol within the liver, other enzymes, such as cytochrome P4502E1
      and catalase, also contributes to the production of acetaldehyde from ethanol
      oxidation. In turn, acetaldehyde is metabolized by the enzyme aldehyde
      dehydrogenase. In animal studies, acetaldehyde is mainly reinforcing particularly
      when injected directly into the brain. In humans, genetic polymorphisms of the
      enzymes alcohol dehydrogenase and aldehyde dehydrogenase are also associated with
      alcohol drinking habits and the incidence of alcohol abuse. From these human
      genetic studies, it has been concluded that blood acetaldehyde accumulation
      induces unpleasant effects that prevent further alcohol drinking. It is therefore
      speculated that acetaldehyde exerts opposite hedonic effects depending on the
      localization of its accumulation. In the periphery, acetaldehyde is primarily
      aversive, whereas brain acetaldehyde is mainly reinforcing. However, the
      peripheral effects of acetaldehyde might also be dependent upon its peak blood
      concentrations and its rate of accumulation, with a narrow range of blood
      acetaldehyde concentrations being reinforcing.

PMID- 15164088
TI  - The 'effectiveness' scale--therapeutic outcome of pharmacologic therapies for ED:
      an international consensus panel report.
AB  - Despite availability of outcome measures and scales for assessing erectile
      dysfunction (ED) treatment efficacy, guidelines are not available for assessing
      broader therapeutic outcomes or defining treatment failure in ED. An
      International Consensus Advisory Panel was convened to develop guidelines,
      definitions and a new algorithm for evaluating treatment effectiveness in ED.
      These new guidelines are recommended for use in both research and clinical
      practice. A multidisciplinary, international panel, consisting of 11 senior
      researchers and clinicians, was convened to address pertinent issues concerning
      therapeutic outcome assessment for ED. The panel utilized a modified Delphi
      method of consensus development and proposed a new model for outcomes assessment.
      This model is inherently testable, using existing instruments and current methods
      of assessment. Following a comprehensive literature review and discussion, the
      Panel recommended adoption of a new treatment effectiveness conceptual framework
      or theoretical model for assessing therapeutic outcomes in ED. Treatment
      effectiveness is presumed to be a combined function of two other factors,
      treatment response and treatment satisfaction. Treatment response is based on the
      combined assessment of efficacy and tolerability, and treatment satisfaction on
      the combined assessment of patient and partner satisfaction. Taken together,
      these two domains define an overall domain of treatment effectiveness. This
      therapeutic index would be derived by independently assessing treatment efficacy
      and satisfaction by means of event logs, questionnaires or the more typical
      patient interview methods. In conclusion, the Ad Hoc Advisory Consensus Panel
      recommends adoption of a new framework or conceptual model for conducting ED
      outcome trials or clinical research. The concept of 'treatment effectiveness' is
      proposed as a new 'umbrella concept' or distal outcome to be evaluated.

PMID- 15164087
TI  - Aging and pathogenesis of erectile dysfunction.
AB  - The prevalence and the severity of erectile dysfunction (ED) increase with
      advancing age; different pathogenetic factors could contribute to age-related ED.
      We studied organic, relational and intrapsychic components of ED as a function of
      patients' age in a consecutive series of 977 patients with ED, using the
      specifically designed structured interview SIEDY. A complete physical examination
      and a series of biochemical, hormonal, psychometric and penile vascular tests
      were also performed. Relational factors seems to be more relevant in patients
      aged over 60 y, while intrapsychic disturbances play a major role in younger
      subjects. Organic factors are the most important determinant of ED in all age
      groups, but their contribution is more important in older patients. In fact,
      basal and dynamic peak cavernosal velocity at Doppler ultrasound penile
      examination was reduced in older patients. Among hormonal factors, the body mass
      index-dependent reduction of testosterone in older patients does not seem to play
      a crucial role in the pathogenesis of ED. No significant correlation was observed
      between testosterone level and the severity of ED, although patients reporting
      hypoactive sexual desire showed significantly lower testosterone levels when
      compared with the rest of the sample. A better understanding of the relative
      contribution of age-related pathogenetic factors of ED could be of help in the
      design of appropriate therapeutic approaches.

PMID- 15164089
TI  - Effects of age, menopause, and comorbidities on neurological function of the
      female genitalia.
AB  - The aim of this study was to investigate the effects of age, menopause, and
      comorbidities on neurological function of the female genitalia using a
      noninvasive, validated technique. In all, 58 consecutive women were enrolled in
      the study. Biothesiometry was performed at five genital sites and one peripheral
      site with S2 dermatome distribution. Kruskal-Wallis one-way ANOVA on ranks was
      used to evaluate the relationship between age and vibratory sensation. Bivariate
      and regressional analyses were performed to evaluate the effects of age,
      menopause and comorbidities on genital sensation. The mean age was 44.6+14.8 y
      (range 20-78 y). Vibration thresholds increased with advancing age at all six
      sites. Multilinear regression analysis indicated that menopause and increasing
      age negatively affect sensation. History of herniated lumbar disc, vaginal
      delivery, and diabetes variably affected genital sensation. There is a
      significant increase in vibration thresholds (indicating worsening neurological
      function) in women as they age and undergo menopause. Biothesiometry is a
      technique for evaluating genital neurological function in women with coexisting
      morbidities.

PMID- 15164091
TI  - Comparative analysis of genomic HSV vectors for gene delivery to motor neurons
      following peripheral inoculation in vivo.
AB  - The use of viral vectors for gene delivery to motor neurons in vivo has been
      hampered by the need to perform invasive surgery to inject directly the vector
      into the anterior horn of the spinal cord. Here, we have characterized the
      features of herpes simplex virus-1 (HSV)-derived vectors, in terms of gene
      mutations and promoter constructs, that are required to allow efficient
      transduction of motor neurons following a relatively noninvasive peripheral
      administration via sciatic nerve or footpad injection. Owing to the wide variety
      of animal models used to study neurodegenerative diseases of motor neurons, we
      analysed the effectiveness of these vectors in adult mice and adult and neonatal
      rats. We tested viruses with differing degrees of disablement based on the 1764
      backbone (deleted for ICP34.5 and an insertional inactivation in VP16) rendered
      completely replication incompetent by the deletion of the essential immediate
      early genes ICP27 and/or ICP4. In the adult mouse, prolonged gene expression in
      motor neurons was obtained after sciatic nerve inoculation with a vector
      defective in ICP4 and ICP27. In the adult rat, both the vector defective in ICP4
      and the vector defective in ICP4 and ICP27 were capable of transducing motor
      neurons for extended periods of time during viral latency. This study
      demonstrates the feasibility of using HSV vectors for persistent transgene
      expression in motor neurons in a safe and nontoxic manner following peripheral
      administration. These vectors are potentially useful tools to investigate the
      functions of genes involved in motor neuronal survival and regeneration in models
      of motor neuron diseases in vivo.

PMID- 15164090
TI  - Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and
      Central Africa.
AB  - For the development of human immunodeficiency virus type 1 (HIV-1) vaccines,
      traditional approaches inducing virus-neutralizing antibodies have so far failed.
      Thus the effort is now focused on elicitation of cellular immunity. We are
      currently testing in clinical trials in the United Kingdom and East Africa a T
      cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in
      a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA).
      Here, we describe engineering and preclinical development of a second immunogen
      RENTA, which will be used in combination with the present vaccine in a four
      component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a
      fusion protein derived from consensus HIV clade A sequences of Tat, reverse
      transcriptase, Nef and gp41. We inactivated the natural biological activities of
      the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA
      vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys
      broadening of HIVA-elicited T-cell responses by a parallel induction of HIVA- and
      RENTA-specific responses recognizing multiple HIV epitopes.

PMID- 15164092
TI  - Seeing the gene therapy: application of gene gun technique to transfect and
      decolour pigmented rat skin with human agouti signalling protein cDNA.
AB  - We developed a gene gun method for the transfer of human agouti signalling
      protein (ASP) cDNA to alter rat skin colour in vivo. Human ASP cDNA was cloned
      into a modified cytomegalovirus plasmid and delivered to the skin of Long-Evans
      rats by gene gun bombardment. Skin pigmentation, body weight and blood sugar of
      ASP cDNA-transfected rats were recorded against the control group, which were
      injected with plasmids encoding for green fluorescent protein. The treated skin
      showed lighter skin colour after 3 days of ASP gene transfection. This
      depigmentation effect was most prominent on day 14 and the skin gradually
      returned to its original pigmentation by day 28. Successful transfection of ASP
      gene in skin and hair follicles, as well as downregulation of melanocortin-1
      receptor (MC1R) and tyrosinase expression upon treatment, was confirmed using
      immunohistochemistry and Western blot analysis. Body weight and blood sugar in
      the treated rats did not show statistically significant differences as compared
      to control groups. These observations demonstrate that gene transfer using the
      gene gun method can induce high cutaneous ASP production and facilitate a switch
      from dark to fair colour without systemic pleiotropic effects. Such a colour
      switch may be that ASP is acting in a paracrine fashion. In addition, this study
      verifies that ASP exerts its functions by acting as an independent ligand that
      downregulates the melanocyte MC1R and tyrosinase protein in an in vivo system.
      Our result offers new, interesting insights about the effect of ASP on
      pigmentation, providing a novel approach to study the molecular mechanisms
      underlying skin melanogenesis.

PMID- 15164093
TI  - Targeting cathepsin L (CL) by specific ribozymes decreases CL protein synthesis
      and cartilage destruction in rheumatoid arthritis.
AB  - The present study was undertaken to examine whether ribozymes cleaving
      specifically cathepsin L (CL) mRNA are able to decrease the synthesis of CL
      protease in rheumatoid arthritis synovial fibroblasts (RA-SF) and thereby reduce
      the invasiveness into cartilage both in vitro and in the SCID mouse
      coimplantation model of RA. Two different ribozymes that cleave CL mRNA
      specifically at positions 533 (RzCL533) and 790 (RzCL790) were generated. Using
      retroviral gene transfer, RA-SF were transduced with the ribozyme constructs or
      the empty vector. To examine the effect of the ribozymes on the mRNA level,
      quantitative analysis for CL mRNA was performed using real-time PCR. For
      evaluation on the protein level, ELISA using specific anti-CL antibodies was
      performed. In addition, transduced RA-SF were examined in vitro in a three
      dimensional destruction assay evaluating their ability to degrade extracellular
      matrix produced by human chondrocytes. Matrix destruction was monitored by the
      release of soluble glycosaminoglycans (sGAG). Using the in vivo SCID mouse
      coimplantation model of RA, RzCL533-transduced RA-SF and control cells were
      coimplanted with human cartilage for 60 days. After being killed, invasion of RA
      SF into the cartilage was evaluated by using a semiquantitative score.
      Transduction of RA-SF with RzCL533 and RzCL790 ribozymes decreased significantly
      the expression of CL mRNA to 44% (range 25-62%) and 20% (range 1-43%),
      respectively, when compared to mock-transduced cells. The protein concentration
      of CL in the cell culture supernatants of transduced RA-SF was decreased from
      16.0 ng/ml in the mock constructs to 4.1 and 8.2 ng/ml (mean), respectively.
      Using the in vitro cartilage destruction assay, the release of sGAG decreased to
      46 and 60%, respectively, after 14 days when compared to mock-transduced cells.
      In the SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF revealed a
      significant lower cartilage invasion when compared to mock and untransduced
      cells. Using retroviral gene transfer, ribozymes cleaving CL mRNA inhibit
      specifically the synthesis of this matrix-degrading enzyme and reduce cartilage
      destruction in in vitro and in vivo models. Our study therefore suggests that
      ribozymes targeting CL could be a novel and efficient tool to inhibit joint
      destruction in RA.

PMID- 15164094
TI  - Complete reversal of multidrug resistance by stable expression of small
      interfering RNAs targeting MDR1.
AB  - Overexpression of P-glycoprotein, encoded by the MDR1 gene, confers multidrug
      resistance (MDR) on cancer cells and is a frequent impediment to successful
      chemotherapy. Recent developments in the use of small interfering RNAs to inhibit
      specific protein expression have highlighted their potential use as therapeutic
      agents. We have expressed two different short hairpin RNAs from stably integrated
      plasmids in doxorubicin-resistant K562 leukaemic cells. The MDR1-targeted RNA
      interference (RNAi) resulted in decreased MDR1 mRNA, abolished P-glycoprotein
      expression, and completely reversed the MDR phenotype to that of the drug
      sensitive K562 parental line. This study demonstrates that MDR, which is solely
      due to overexpression of P-glycoprotein, can be reversed by RNAi. These target
      sequences can in the future be integrated into gene therapy vectors with
      potential clinical application.

PMID- 15164095
TI  - Enhanced efficacy of Escherichia coli nitroreductase/CB1954 prodrug activation
      gene therapy using an E1B-55K-deleted oncolytic adenovirus vector.
AB  - Viruses that replicate selectively in cancer cells constitute an exciting new
      class of anticancer agent. The conditionally replicating adenovirus (CRAd)
      dl1520, which lacks the E1B-55K gene, has elicited significant clinical responses
      in humans when used in combination with chemotherapy. A convergent development
      has been to use replication-defective viruses to express prodrug-activating
      enzymes in cancer cells. This can sensitize the cancer to prodrug, but depends
      upon achieving sufficient level, distribution and specificity of enzyme
      expression within the tumour. In this study, we have expressed the prodrug
      activating enzyme nitroreductase (NTR) in the context of an E1B-55K-deleted
      adenovirus, CRAd-NTR(PS1217H6). We show that CRAd-NTR(PS1217H6) retains oncolytic
      growth properties, and expresses substantially more NTR than a comparable,
      replication-defective adenovirus. The combination of viral oncolysis and NTR
      expression results in significantly greater sensitization of SW480 and WiDr
      colorectal cancer cells to the prodrug CB1954 in vitro. In vivo, CRAd
      NTR(PS1217H6) was shown to replicate in subcutaneous SW480 tumour xenografts in
      immunodeficient mice, resulting in more NTR expression and greater sensitization
      to CB1954 than with replication-defective virus. Combination therapy of CRAd
      NTR(PS1217H6) with CB1954 reduced tumour growth from 13.5- to 2.8-fold over 5
      weeks, and extended median survival from 42 to 81 days, compared with no
      treatment.

PMID- 15164096
TI  - Transgenic rescue of Krabbe disease in the twitcher mouse.
AB  - The twitcher mouse is a natural model of Krabbe disease caused by
      galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the
      twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis
      were only partially successful. Here, we report the transgenic (tg) rescue of the
      twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg
      mice exhibited growth, motor function, and fertility similar to those of
      nonaffected animals. These animals had normal levels of GALC activity in brain
      and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC
      expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was
      only partially cleared. Nonetheless, these mice have been maintained for over 1
      year without any sign of disease. Since pathological damage associated with GALC
      deficiency is confined to the nervous system, our work represents the first
      successful rescue of the twitcher mouse and opens the possibility of developing
      novel therapeutic approaches.

PMID- 15164097
TI  - Improved transduction of primary murine hepatocytes by recombinant adeno
      associated virus 2 vectors in vivo.
AB  - Adeno-associated virus 2 (AAV) vectors are currently in use in Phase I/II
      clinical trials for gene therapy of cystic fibrosis and hemophilia B. Although
      100% of murine hepatocytes can be targeted by AAV vectors, the transgene
      expression is limited to approximately 5% of hepatocytes. Since the viral genome
      is a single-stranded DNA, and single strands of both polarities are encapsidated
      with equal frequency, it has been suggested that failure to undergo DNA strand
      annealing accounts for the lack of efficient transgene expression. We and others,
      on the other hand, have proposed that failure to undergo viral second-strand DNA
      synthesis attributes to the observed low efficiency of transgene expression. We
      have previously documented that a cellular protein, designated FKBP52, when
      present in phosphorylated forms, inhibits the viral second-strand DNA synthesis,
      and consequently, limits transgene expression in nonhepatic cells, whereas
      unphosphorylated forms of FKBP52 have no effect. To further evaluate whether
      phosphorylated FKBP52 is also involved in regulating AAV-mediated transgene
      expression in murine hepatocytes, we generated transgenic mice overexpressing the
      cellular T-cell protein tyrosine phosphatase (TC-PTP) protein, known to catalyze
      dephosphorylation of FKBP52, as well as mice deficient in FKBP52. We demonstrate
      here that dephosphorylation of FKBP52 in TC-PTP transgenic (TC-PTP-TG) mice, and
      removal of FKBP52 in FKBP52-knockout (FKBP52-KO) mice results in efficient
      transduction of murine hepatocytes following tail-vein injection of recombinant
      AAV vectors. We also document efficient viral second-strand DNA synthesis in
      hepatocytes from both TC-PTP-TG and FKBP52-KO mice. Thus, our data strongly
      support the contention that the viral second-strand DNA synthesis, rather than
      DNA strand-annealing, is the rate-limiting step in the efficient transduction of
      hepatocytes, which should have implications in the optimal use of recombinant AAV
      vectors in human gene therapy.

PMID- 15164098
TI  - Infectious delivery of the 132 kb CDKN2A/CDKN2B genomic DNA region results in
      correctly spliced gene expression and growth suppression in glioma cells.
AB  - The expression of genes from genomic loci can be relatively complex, utilizing
      exonic, intronic and flanking sequences to regulate tissue and developmental
      specificity. Infectious bacterial artificial chromosomes (iBACs) have been shown
      to deliver and express large genomic loci (up to 135 kb) into primary cells for
      functional analyses. The delivery of large genomic DNA inserts allows the
      expression of complex loci and of multiple splice variants. Herein, we
      demonstrate for the first time that an iBAC will deliver and correctly express in
      human glioma cells the entire CDKN2A/CDKN2B genomic region, which encodes for at
      least three important cell-cycle regulatory proteins (p16(INK4a), p14(ARF) and
      p15(INK4b)). Two of these proteins are expressed from overlapping genes,
      utilizing alternative splicing and promoter usage. The delivered locus expresses
      each gene at physiological levels and cellular responses (apoptosis versus growth
      arrest) occur dependent on cellular p53 status, as expected. The work further
      demonstrates the potential of the iBAC system for the delivery of genomic loci
      whose expression is mediated by complex splicing and promoter usage both for gene
      therapy applications and functional genomics studies.

PMID- 15164099
TI  - Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and
      alters tumor vessel ultrastructure.
AB  - Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually
      fatal within 1 year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we
      have developed a novel drug delivery method in which naked plasmid DNA is
      selectively targeted to brain tumors via intra-arterial injection. Using a
      plasmid encoding the antiangiogenic endostatin, transgene expression can be
      detected in tumor cells in vivo, and therapeutic efficacy is observed.
      Administration of this plasmid resulted in an 80% tumor volume reduction 1 week
      after treatment and enhanced survival time by up to 47%. Treated tumors exhibited
      a 40% decrease in the number of tumor vessels; ultrastructural analysis of
      remaining tumor vessels demonstrated a number of changes including markedly
      narrowed or collapsed lumens. We conclude that intra-arterial injection of
      plasmids selectively targets therapeutic genes to CNS neoplasms. This method of
      gene therapy holds promise for the treatment of these highly malignant brain
      tumors.

PMID- 15164100
TI  - A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia
      stimulated TNF alpha production.
AB  - CD14, a pattern recognition receptor on monocyte and macrophage, plays a central
      role in innate immunity through recognition of bacterial lipopolysaccharide and
      initiation of inflammatory response. Recently, CD14/-260C>T promoter gene
      polymorphism has been found to be related to a risk of inflammatory diseases. Our
      results showed that the C allele frequency among Chinese in Taiwan was lower than
      those in Western countries. The membrane CD14 expression was significantly higher
      in TT as compared with CT and CC genotypes (P=0.034, 0.044, respectively). There
      was a higher level of soluble CD14 in TT and CT genotypes than in CC genotypes.
      In addition, TNFalpha production in whole blood was significantly higher in TT
      genotype than in CC genotype after stimulation by Chlamydiae. In conclusion, the
      single base pair polymorphism of CD14 promoter gene is associated with CD14
      expression and Chlamydia-stimulated TNFalpha production, and may thus play some
      role in the chlamydia-induced inflammatory response.

PMID- 15164101
TI  - MICA intron 1 sequences of conserved extended HLA haplotypes: implications for
      sequencing-based typing.
AB  - The human major histocompatibility complex (MHC) class I chain-related gene A
      (MICA) has a high degree of genetic diversity. Several methods have been used in
      MICA typing. Recent studies reported different results for the same reference
      cell lines typed by different methods. By searching the GenBank, we found an
      indel polymorphism in MICA intron 1 corresponding to the area where one of the
      sequencing-based typing primers used by others is located. We investigated this
      polymorphism in 43 reference samples by primer cycle sequencing. This approach
      revealed three haplotype-specific patterns of polymorphisms in intron 1. This
      study provided evidence that one of the primers commonly used in MICA typing may
      fail to amplify both alleles in certain heterozygous combinations. Our data
      showed a correlation between the three patterns in MICA intron 1 and exon 5 short
      tandem repeat (STR) alleles. Being neutral ones, the intron 1 and STR
      polymorphisms appeared to mark the ancestral lineages better than the coding
      region polymorphisms.

PMID- 15164102
TI  - Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer
      associations with disease.
AB  - Alleles of HLA class II genes DQB1, DQA1, and DRB1 in the MHC region are major
      determinants of genetic predisposition to type 1 diabetes (T1D). Several alleles
      of each of these three loci are associated with susceptibility or protection from
      disease. In addition, relative risks for some DR-DQ genotypes are not simply the
      sum or product of the single haplotype relative risks. For example, the risk of
      the DRB1*03-DQB1*02/DRB1*0401-DQB1*0302 genotype is often found to be higher than
      for the individual DRB1*03-DQB1*02 and DRB1*0401-DQB1*0302 homozygous genotypes.
      It has been hypothesized that this synergy or epistasis occurs through formation
      of highly susceptible trans-encoded HLA-DQ(alpha 1, beta 1) heterodimers. Here,
      we evaluated this hypothesis by estimating the disease associations of the range
      of DR-DQ genotypes and their inferred dimers in a large collection of nuclear
      families. We determined whether the risk of haplotypes in DRB1*0401-DQB1*0302
      positive genotypes relative to the DRB1*03-DQB1*02-positive genotypes is
      different from that of DRB1*01-DQB1*0501, which we used as a baseline reference.
      Several haplotypes showed a different risk compared to DRB1*01-DQB1*0501, which
      correlated with their ability to form certain trans-encoded DQ dimers. This
      result provides new evidence for the potential importance of trans-encoded HLA DQ
      molecules in the determination of HLA-associated risk in T1D.

PMID- 15164104
TI  - Epidemiological study of the influence of family and socioeconomic status in
      disorders of eating behaviour.
AB  - OBJECTIVE: To analyse the differences in family functioning and socioeconomic
      status between subjects with disorders of eating behaviour and the healthy
      population, considering the possible relationship of these factors with the
      psychic characteristics of patients, with consumption of various substances, and
      with sexual practices. DESIGN: Case-control study. SETTING: 'Puerta del Mar'
      University Hospital (Andalusia, Spain). SUBJECTS: Conducted on a sample of 120
      patients with AN and BN, and 240 controls with an identical distribution by age
      and sex. INTERVENTIONS: SCOFF, eating disorder inventory (EDI), Apgar family and
      socioeconomic questionnaires are utilised. RESULTS: Patients with disorders of
      eating behaviour present greater family dysfunctioning than controls; among
      cases, this difference is greater in the acute forms, but there are no
      differences between recent situations or crises due to previous episodes. Family
      dysfunction is associated with higher scores of multiple subscales of the EDI,
      which is corroborated on analysing each of the Apgar parameters independently.
      Family functioning is not associated with other variables such as breast-feeding
      or consumption of toxic substances. Socioeconomic status does not differentiate
      cases from controls, or acute situations from evolving ones, or new episodes from
      other crisis episodes, although differences may be found in the psychic
      manifestations according to social class. CONCLUSIONS: It is confirmed that
      family functioning has an influence in these types of disorder, in their
      evolution and in the psychic characteristics of the patients, without any
      evidence being found of a relationship between these disorders and socioeconomic
      status.

PMID- 15164105
TI  - Body composition in patients with short bowel syndrome: an assessment by
      bioelectric impedance spectroscopy (BIS) and dual-energy absorptiometry (DXA).
AB  - OBJECTIVE: To describe body composition in patients with short bowel syndrome
      (SBS) by using bioelectric impedance spectroscopy (BIS), dual-energy X-ray
      absorptiometry (DXA) measurements and anthropometrical-derived estimates.
      SUBJECTS: In all, 19 patients were included, mean age 54 y, range 36-77
      (F/M=11/8). Mean BMI was 21.5 kg/m(2). Eight patients were on home parenteral
      nutrition (HPN). METHODS: Total body water (TBW), intracellular water and
      extracellular water were assessed by BIS. TBW were derived from DXA. Fat-free
      mass (FFM) was assessed by BIS and DXA. TBW and FFM were predicted according to
      an empirical formula. Differences were analysed using the Bland-Altman method.
      RESULTS: The mean difference between TBW (DXA) and TBW (BIS) was -1.1 l in women
      and -1.8 l in men. For FFM, the mean difference between FFM (DXA) and FFM (BIS)
      was -1.7 kg in women and -2.5 kg in men. The mean difference between TBW (DXA)
      and TBW (BIS) for all patients was -1.2 l and limits of agreement were (-7.80
      5.40). Hydration of FFM assessed by BIS gave a mean of 0.75 (0.08). CONCLUSION:
      The limits of agreement (Bland-Altman) between DXA and BIS were wide, indicating
      that methods are not interchangeable, which limits its clinical utility. Most of
      our patients with SBS were maintained in a stable clinical condition within
      normal limits of body weight and BMI. FFM and TBW did not appear to be altered in
      ileostomates or those on HPN.

PMID- 15164103
TI  - Nutrient supplementation with polyunsaturated fatty acids and micronutrients in
      rheumatoid arthritis: clinical and biochemical effects.
AB  - OBJECTIVE: To investigate in a double-blind placebo-controlled, parallel group
      study, the effects of a nutrient supplement, containing, among other ingredients,
      the omega-3 fatty acids eicosapentaenoic acid (1.4 g EPA), docosahexaenoic acid
      (0.211 g DHA), omega-6 fatty acid gamma-linolenic acid (0.5 g GLA) and
      micronutrients in patients with active rheumatoid arthritis (RA). DESIGN,
      SUBJECTS AND INTERVENTION: RA patients were randomized to receive either daily
      liquid nutrient supplementation or placebo for 4 months. The primary end point
      was the change in tender joint count at 2 and 4 months. Other clinical variables
      included swollen joint count, visual analogue scales for pain and disease
      activity, grip strength, functionality score and morning stiffness. Biochemical
      parameters included plasma concentrations of PUFA and vitamins C and E. SETTING:
      Outpatient university clinic. RESULTS: In all, 66 patients enrolled, 55 completed
      the study. No significant change from baseline in tender joint count or any of
      the other clinical parameters was detected in either group. Patients receiving
      nutrient supplementation, but not those receiving placebo, had significant
      increases in plasma concentrations of vitamin E (P=0.015), and EPA, DHA and
      docosapentaenoic acid concomitant with decreases of arachidonic acid (P=0.01).
      Intergroup differences for PUFA and vitamin E were significantly different
      (P=0.01 and 0.03, respectively). CONCLUSIONS: This double-blind, placebo
      controlled study in RA patients did not show superior clinical benefit of daily
      nutrient supplementation with EPA, GLA and micronutrients at the doses tested as
      compared to placebo. The study adds information regarding doses of omega-3 fatty
      acids, below which anti-inflammatory effects in RA are not seen.

PMID- 15164107
TI  - Dietary intakes of adults in the Netherlands by childhood and adulthood
      socioeconomic position.
AB  - OBJECTIVE: To determine whether there are socioeconomic differences in the
      intakes of total fat, fatty acids and fruit among adults in the Netherlands using
      childhood (parental) and participant's own socioeconomic position (SEP).
      Furthermore, to quantify the independent effects of childhood and adulthood SEP
      on dietary behavior in adulthood. DESIGN: Cross-sectional study among
      participants in the GLOBE study. SUBJECTS: A total of 2512 men and women, aged 25
      78 y, living in a region in the southeast Netherlands. METHODS: Dietary intakes
      were collected by an interviewer-administered quantitative food frequency
      questionnaire. Average daily intakes of total energy, total, saturated,
      monounsaturated, polyunsaturated fat and fruit were calculated. The highest
      educational level was used to classify the participant's adulthood SEP. Parental
      indicators (mother's education and father's occupation when participants were 12
      y of age) were used to classify childhood SEP. RESULTS: Males with lower levels
      of education had moderately higher energy intakes than their more educated
      counterparts, but did not differ in their intakes of total fat, fatty acids and
      fruit. Among females, the least educated groups had marginally higher intakes of
      total and monounsaturated fat than the most educated group, and were less likely
      to consume fruit. For most of these significant differences, the participant's
      own education demonstrated independent effects that were consistent with chronic
      disease inequalities. A small residual effect of mother's education was also
      demonstrated for intakes of some nutrients for males and females, and for fruit
      consumption among females. However, the effect size of mother's education was
      rather small and not always consistent with disease inequalities. CONCLUSIONS:
      The results imply that socioeconomic disparities in intakes of some dietary
      factors may contribute to inequalities in chronic disease. Adulthood SEP
      potentially has a more direct influence on dietary intake inequalities than
      childhood SEP.

PMID- 15164106
TI  - Effect of free plant sterols in low-fat milk on serum lipid profile in
      hypercholesterolemic subjects.
AB  - OBJECTIVE: To determine the effect of nonesterified, nonhydrogenated plant
      sterols solubilized in a partly vegetable oil-filled low-fat milk on serum low
      density lipoprotein cholesterol (LDL) in mildly hypercholesterolemic patients.
      DESIGN: Double-blind, randomized, placebo-controlled three-arm crossover study.
      SETTING: Outpatient clinical trial. SUBJECTS: A total of 138 patients were
      screened, providing 81 patients for randomization; 71 patients completed the
      study. INTERVENTIONS: The study product was a 500 ml milk blend with or without
      nonesterified, nonhydrogenated sterols. The daily consumption of sterols in the
      three groups was 0 g/day, control group (C); 1.2 g/day, (Lo); or 1.6 g/day, (Hi),
      respectively. The patients were randomly assigned to one of three different
      treatment sequences. Each intervention period was 4 weeks. The total study
      duration was 12 weeks. RESULTS: The milk product was well tolerated. The placebo
      adjusted mean reduction in LDL was 7.13+/-12.31 and 9.59+/-12.44% (mean+/-s.d.)
      for Lo and Hi groups, respectively (P<0.0001); there was no statistically
      significant difference in LDL lowering for the Lo and Hi groups. There were no
      significant changes in serum vitamin E or carotenoid concentrations after
      standardization with LDL cholesterol during the study period. CONCLUSION: The
      present study shows for the first time a substantial reduction in LDL cholesterol
      with a new, partly vegetable oil-filled 1.2% low-fat milk product, containing
      nonesterified plant sterols from soybean oil, in a randomized, placebo-controlled
      trial. This result encourages further development of novel low-fat dairy products
      containing free plant sterols for future use in cholesterol-lowering initiatives.

PMID- 15164109
TI  - Waist circumference, body mass index, hip circumference and waist-to-hip ratio as
      predictors of cardiovascular disease in Aboriginal people.
AB  - OBJECTIVE: To investigate waist circumference (WC), waist-hip ratio, hip
      circumference and body mass index (BMI) as risk factors for cardiovascular
      disease in Aboriginal Australians. METHODS: This cohort study included 836 adults
      aged 20-74 y in a remote Aboriginal community. WC, waist-hip ratio, hip
      circumference and BMI were obtained from a screening program. The participants
      were followed for up to 10 y for cardiovascular events. A Cox regression model
      was used to calculate the rate ratio (RR) and 95% confidence interval (CI) for
      the first-ever cardiovascular event (fatal and nonfatal). RESULTS: RRs for the
      first-ever cardiovascular event were 1.31 (95% CI: 1.11, 1.54), 1.29 (95% CI:
      1.09,1.53), 1.28 (95% CI: 1.08, 1.52) and 1.10 (95% CI: 0.93, 1.30) per standard
      deviation increase in WC, BMI, hip circumference and waist-hip ratio,
      respectively, after adjustment for diabetes mellitus, total cholesterol, systolic
      blood pressure and smoking status. WC, BMI and hip circumference were
      significantly associated with cardiovascular risk, independent of other
      cardiovascular risk factors. Dividing each of the four parameters into quartiles,
      WC had the highest likelihood statistics (12.76) followed by BMI (11.45), hip
      circumference (10.57) and waist-hip ratio (3.15) for predicting first CV events.
      CONCLUSION: WC, BMI and hip circumference are associated with cardiovascular
      outcome, independent of traditional risk factors. However, WC appears to be a
      better predictor for cardiovascular risk than other parameters. Waist-hip ratio
      is not as useful as other measurements.

PMID- 15164108
TI  - Reduction of dietary saturated fatty acids correlates with increased plasma
      lecithin cholesterol acyltransferase activity in humans.
AB  - OBJECTIVE: Increased HDL-cholesterol (HDL-C) concentrations have been associated
      with lower coronary heart disease risk. On the other hand, dietary fats are known
      to influence the fatty acid profile of plasma lipids, including phospholipids
      that are substrates of lecithin cholesterol acyltransferase (LCAT), an important
      enzyme in HDL metabolism. The purpose of this study was to examine the
      association between the saturated fatty acid (SFA) intake and LCAT activity.
      DESIGN: An interventional study was performed in a monk community of 25 men.
      SETTING: A French monk community, South West of France. SUBJECTS AND
      INTERVENTIONS: The basal diet of the study cohort contained SFA in a proportion
      of 13.5% of their total energy intake (TEI). They were submitted to two
      experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A)
      or 11% (diet B), each lasting 5 weeks. RESULTS: The elevation of SFA in diet B
      was mainly obtained by decreasing carbohydrates. The only significant difference
      among total fats between diets A and B was the myristic acid content (0.6 and
      1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a
      significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and
      LCAT activity both decreased (P<0.02). CONCLUSION: Altogether, these results are
      consistent with a negative effect of SFA on reverse cholesterol transport.

PMID- 15164110
TI  - Fetal growth is directly related to maternal anthropometry and placental volume.
AB  - OBJECTIVE: To describe the influence of maternal weight and weight gain,
      placental volume and the rate of placental growth in early pregnancy on fetal
      dimensions measured sonographically. DESIGN: In a prospective study, 712 women
      were recruited from the antenatal clinic of the University Hospital of the West
      Indies. Data analysis was confined to 374 women on whom measurements of the
      placental volume at 14, 17 and 20 weeks gestation were complete. Measurements of
      maternal anthropometry and fetal size (by ultrasound) were performed. Weight gain
      in pregnancy between the first antenatal visit (8-10 weeks) and 20 weeks
      gestation, and the rate of growth of the placenta between 14-17 and 17-20 weeks
      gestation were calculated. MAIN OUTCOME MEASURES: Fetal anthropometry (abdominal
      and head circumferences, femoral length, and biparietal diameter) at 35 weeks
      gestation. RESULTS: Lower maternal weight at the first antenatal visit was
      associated with a significantly smaller placental volume at 17 and 20 weeks
      gestation (P<0.002 and <0.0001 respectively). In all women, maternal weight gain
      was directly related to fetal anthropometry. Placental volume at 14 weeks
      gestation and the rate of growth of the placenta between 17 and 20 weeks
      gestation were significantly related to all four fetal measurements. CONCLUSION:
      This study has provided evidence that both placental volume, and the rate of
      placental growth may influence fetal size. These effects are evident in the first
      half of pregnancy, and appear to be mediated through maternal weight and weight
      gain.

PMID- 15164111
TI  - Iron status in 2-year-old Icelandic children and associations with dietary intake
      and growth.
AB  - OBJECTIVE: To investigate the effects of food and nutrient intake at 2 y and
      growth from birth on iron status at 2 y in a population with high birth weight.
      DESIGN: In a cross-sectional study, children's food consumption and body size
      measurements were recorded and blood samples taken. Weighed 3-day food records
      were used to analyse food and nutrient intake. SETTING: Children were recruited
      from across Iceland from the Icelandic National Registry by the University of
      Iceland, Computing Services. The children in the sample were born over a 1-y
      period. SUBJECTS: Parents of randomly selected 2-year-old children (n=130) were
      contacted, and 72% (n=94) participated. Blood samples were analysed in 76% (n=71)
      of participating children. RESULTS: In total, 9% of the children were iron
      deficient (serum ferritin (SF)<12 microg/l and mean corpuscular volume (MCV) <74
      fl) and 1.4% were also anaemic (Hb<105 g/l), while 27% of children were iron
      depleted (SF<12 microg/l). Iron status indices were negatively associated with
      cow's milk consumption. Half of children consuming>500 g cow's milk/day (n=10)
      were iron-deficient, while one child in 58 consuming<500 g cow's milk/day had
      iron deficiency (P<0.001). In multiple regression analyses, also biscuits and
      crackers consumption was positively associated with MCV. Weight gain from birth
      to 2 y was negatively associated with SF (adjusted R(2)=0.15; P=0.002; n=58).
      Iron-depleted children were heavier than children not iron-depleted (14.7+/-1.3
      vs 13.8+/-1.7 kg; P=0.043), had higher BMI (17.7+/-1.5 vs 16.7+/-1.4 kg/m(2);
      P=0.028) and gained more weight from birth (11.2+/-1.3 vs. 10.0+/-1.6 kg;
      P=0.011). CONCLUSIONS: The results suggest that cow's milk consumption above 500
      g/day should be avoided at the age of 2 y for better iron status. Iron depletion
      at 2 y is associated with faster growth from birth.

PMID- 15164112
TI  - Potential intake of phytosterols/-stanols: results of a simulation study.
AB  - BACKGROUND: Different doses of phytosterols/-stanols up to a maximum of 4.0 g/day
      have been used in human safety studies, whereas only one small-scale study
      investigated some detailed clinical information about consumption levels
      exceeding 8.6 g/day. OBJECTIVE: To determine which population groups are likely
      to be at risk of excessive intakes if liberal enrichment of foods with
      phytosterols/-stanols will be allowed. DESIGN AND SUBJECTS: Cross-sectional study
      among a representative sample (n=23 106) of the Dutch population, aged 20-60 y
      (MORGEN-project, 1993-1997). Phytosterol/-stanol intake was assessed with virtual
      replacement of one to four ordinary foods in the diet with enriched products.
      Percentile values were used to describe the distribution in simulated intake for
      different groups in the population, varying in sociodemographic and health
      characteristics. Multiple linear regression was used to describe the contribution
      of the different population characteristics to the simulated phytosterol/-stanol
      intake. RESULTS: If three commonly consumed products (margarine, cheese, yoghurt)
      were completely replaced, the median daily phytosterol/-stanol intake will be
      about 5.5 g in men and 4.6 g in women. In males, the intake above the 90th
      percentile will exceed 8.6 g/day. Women will approach this level. Especially,
      age, body mass index, socioeconomic status, subjective health, smoking behaviour,
      alcohol consumption, pregnancy (women) and high cholesterol level (men)
      contributed to the variance in the simulated intake (P<0.05), although the total
      explained variance was low (1-3%). CONCLUSIONS: If liberal phytosterol/-stanol
      fortification is allowed, the daily intake might exceed the recommended intake
      level as well as our 'cutoff' level of 8.6 g/day. Postlaunch monitoring to
      identify consumers and real intake levels, refinement of scenario buiding, as
      well as human safety studies for levels above 8.6 g/day are necessary.

PMID- 15164113
TI  - Diet as a risk factor for the development of stress urinary incontinence: a
      longitudinal study in women.
AB  - OBJECTIVE: To assess the association between diet and the onset of stress urinary
      incontinence (SUI) in women aged 40 y plus. DESIGN AND SETTING: The
      Leicestershire MRC Incontinence Study - a prospective longitudinal study of the
      prevalence, incidence and aetiology of urinary symptoms. SUBJECTS AND METHODS: A
      total of 5816 women aged 40 y plus and living in the community. Urinary symptoms
      were reported in a postal questionnaire at baseline and at 1-y follow-up. Dietary
      intake was assessed in a food frequency questionnaire at baseline. RESULTS:
      Intakes of total fat, saturated fatty acids and monounsaturated fatty acids were
      associated with an increased risk of SUI onset 1 y later. Of the micronutrients
      studied, zinc and vitamin B12 were positively associated with SUI onset.
      CONCLUSION: The results from this prospective study suggest there may be an
      aetiological association between certain components of the diet and the onset of
      SUI. The findings need confirming and possible mechanisms to explain these
      associations need further investigation.

PMID- 15164114
TI  - Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation
      for adolescent boys and girls through schools in rural and urban East Java,
      Indonesia.
AB  - OBJECTIVE: High prevalences of vitamin A deficiency and anaemia among adolescents
      warrant interventions. This study evaluated the effectiveness of school-based
      supplementation to reduce anaemia and improve vitamin A status. DESIGN: School
      based, grade-randomized, intervention. SUBJECTS AND SETTING: In all, 1757 girls
      and 1859 boys, aged 12-15 y, in 24 Junior High Schools. INTERVENTIONS: Weekly
      supplementation for 14 weeks with 60 mg iron and 250 microg folate (Fe group;
      n=978), 10 000 IU vitamin A (VA group; n=970) or both (VAFe group; n=1042) to
      subjects in 15 schools, compared to subjects in nine other schools not receiving
      supplements (control; n=626). RESULTS: The baseline anaemia prevalence (Hb <120
      g/l) in girls was 20% (prepubertal) and 26% (pubertal), and in boys 24% (pre
      pubertal) and 11% (pubertal). Serum retinol concentrations were low (<1.05
      micromol/l) in 41% of boys and 45% of girls. The interventions did not increase
      haemoglobin concentrations. Serum retinol concentration of boys, but not girls,
      in the VA group increased (0.33 vs 0.07 micromol/l in controls; P<0.01). The risk
      factors for low serum retinol concentration were lower baseline serum retinol
      concentration (OR 0.02-0.03) with, for girls, nightblindness at baseline (OR
      5.88), and for boys, not receiving vitamin A (OR control: 1.00; VA: 0.37; Fe:
      0.77; VAFe: 0.34) and maternal illiteracy (OR mother never attended school 1.00,
      mother received any formal education 0.17-0.33). CONCLUSIONS: Supplementation
      with vitamin A increased serum retinol concentration of boys. Iron
      supplementation did not change Hb. This appeared to be due to poor compliance,
      and partly related to side effects.

PMID- 15164115
TI  - Poor nutritional status of younger Tibetan children living at high altitudes.
AB  - BACKGROUND: The growth, development and nutrition of children in Tibet with high
      altitude and unique traditional culture have recently gained attention. However,
      few researches are available on the nutritional status of younger children of
      Tibet. OBJECTIVE: The objective of the study was to evaluate the nutritional
      status of children below 36 months old in Tibet by means of anthropometry.
      DESIGN: The cross-sectional survey was conducted between August and September in
      1999 and a sample of 1655 children below 36 months old was obtained using a
      stratified multistage cluster random sampling method from a total of seven
      districts of Tibet. Height, weight and hemoglobin concentration were measured and
      at the same time related sociodemographic and environmental information were
      collected. NCHS/CDC/WHO reference data were used to evaluate the nutritional
      status of the entire study children population and estimate the prevalence of
      stunting, underweight and wasting. RESULTS: Compared with the reference of
      NCHS/CDC/WHO, the distributions of HAZ and WAZ shifted to the left significantly
      and the means of HAZ and WAZ were -1.53 and -1.05, respectively, which were
      significantly lower than the reference value. The distribution of WHZ, however,
      was close to that of the reference. The reduction of Z-scores for height and
      weight occurred very early in life and was greatest in the second year after
      birth. The prevalence of malnutrition of children was 39.0% for stunting, 23.7%
      for underweight and 5.6% for wasting, respectively. Rural children had prevalence
      of stunting of 41.4% and underweight of 24.7%, as compared with prevalence of
      stunting of 25.3% and underweight of 18.1% for urban children. Stunting and
      underweight were associated with altitudes. The mean of hemoglobin (Hb) of
      children was 120.4 g/l and rural children had a significantly lower Hb
      concentration (119.9 g/l) than urban children (123.3 g/l). The prevalence of
      anemia seemed higher when using different altitude corrections for Hb to estimate
      the prevalence, but the consequences were uneven. CONCLUSIONS: For Tibetan young
      children, the nutritional status of the entire population is poor and the
      prevalence of malnutrition is higher, especially for stunting. Malnutrition is
      related to high altitudes. Although the Hb concentration is higher induced by
      high altitude, there must be quite a lot of anemic children at high altitudes.
      The relationship between altitude and Hb for children on the Tibetan plateau
      requires further study in order to determine correctly the magnitude of anemia of
      children.

PMID- 15164116
TI  - Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in
      humans.
AB  - OBJECTIVE: To determine the absorption, excretion and metabolism of kaempferol in
      humans. DESIGN: A pharmacokinetic study of kaempferol from endive over 24 h.
      SUBJECTS: Four healthy males and four healthy females. RESULTS: Kaempferol, from
      a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma
      concentration of 0.1 microM, at a time of 5.8 h, indicating absorption from the
      distal section of the small intestine and/or the colon. Although a 7.5-fold
      interindividual variation between the highest and lowest maximum plasma
      concentration was observed, most individuals showed remarkably consistent
      pharmacokinetic profiles. This contrasts with profiles for other flavonoids that
      are absorbed predominantly from the large intestine (eg rutin). An average of
      1.9% of the kaempferol dose was excreted in 24 h. Most subjects also showed an
      early absorption peak, probably corresponding to kaempferol-3-glucoside, present
      at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound
      detected in plasma and urine. Quercetin was not detected in plasma or urine
      indicating a lack of phase I hydroxylation of kaempferol. CONCLUSIONS: Kaempferol
      is absorbed more efficiently than quercetin in humans even at low oral doses. The
      predominant form in plasma is a 3-glucuronide conjugate, and interindividual
      variation in absorption and excretion is low, suggesting that urinary kaempferol
      could be used as a biomarker for exposure.

PMID- 15164117
TI  - Bioavailability and antioxidant effects of olive oil phenols in humans: a review.
AB  - OBJECTIVE: We reviewed the bioavailability and antioxidant effects of phenols
      from extra virgin olive oil. SEARCH STRATEGY: We searched the MEDLINE database
      for the years 1966-2002. To review the bioavailability of olive oil phenols, we
      selected animal and human studies that studied the absorption, metabolism, and
      urinary excretion of olive oil phenols. We also estimated the intake of the
      various phenols in the Mediterranean area. To review the antioxidant effects of
      olive oil phenols, we included human and animal studies on the effect of olive
      oil phenols on markers of oxidative processes in the body. We excluded studies
      without a proper control treatment and studies in which the antioxidant effects
      of phenols could not be disentangled from those of the fatty acid composition of
      olive oil. RESULTS: Bioavailability studies in humans show that the absorption of
      olive oil phenols is probably larger than 55-66 mol%, and that at least 5% is
      excreted in urine as tyrosol and hydroxytyrosol. Animal studies suggest that
      phenol-rich olive oil lowers oxidisability of ex vivo low-density lipoprotein
      (LDL) particles or lowers markers in urine of oxidative processes in the body. In
      five out of seven human studies, however, these effects of phenols were not
      found. There are no data on the phenol concentrations in plasma that are
      attainable by intake of olive oil. We estimated that 50 g of olive oil per day
      provides about 2 mg or approximately 13 micromol of hydroxytyrosol-equivalents
      per day, and that the plasma concentration of olive oil phenols with antioxidant
      potential resulting from such an intake can be at most 0.06 micromol/l. This is
      much lower than the minimum concentrations of these phenols (50-100 micromol)
      required to show antioxidant activity in vitro. CONCLUSION: Although phenols from
      olive oil seem to be well absorbed, the content of olive oil phenols with
      antioxidant potential in the Mediterranean diet is probably too low to produce a
      measurable effect on LDL oxidisability or other oxidation markers in humans. The
      available evidence does not suggest that consumption of phenols in the amounts
      provided by dietary olive oil will protect LDL against oxidative modification to
      any important extent.

PMID- 15164118
TI  - Low bone mass in premenopausal chronic dieting obese women.
AB  - BACKGROUND: Obese premenopausal women are thought to be at low risk for
      osteoporosis due to increased body weight and effects of estrogen on weight
      bearing bone. OBJECTIVE: To examine the effect of restrained eating on obese
      women, we examined bone mineral density (BMD) and content (BMC) of the spine and
      femur in obese women who were restrained eaters, with emphasis on the
      relationship between BMC and determinants of bone mass, and current eating
      behaviors, dietary intake, physical activity, and indices of calcium regulation,
      bone metabolism, stress and inflammation. DESIGN: A total of 78 obese, Caucasian,
      female, restrained eaters, ages 30-45 y, were enrolled in a weight lose program.
      Height, weight, bone turnover markers, serum parathyroid hormone (PTH), cortisol,
      c-reactive protein (CRP), dietary intake, eating behaviors, physical activity,
      and BMD and BMC were measured. SETTING: This study was conducted at the
      University of California, in Davis, CA, USA. RESULTS: In all, 31% of women had
      osteopenia or osteoporosis (OSTEO). In the OSTEO group, 87.5% of women had
      osteoporosis or osteopenia of the lumbar spine and 12.5% of the women had
      osteoporosis or osteopenia in femur. A significant positive correlation between
      BMC and energy expenditure (r=0.256), and a significant negative correlation
      between BMC and number of times on a weight loss diet (r=-0.250) and cognitive
      restraint (r=-0.239) were observed. No significant differences were observed
      between OSTEO women and nonosteoporotic women for current eating behaviors,
      dietary intake, physical activity habits, bone turnover, calcium regulation,
      stress, or inflammation. CONCLUSIONS: Obese restrained eaters are at risk for low
      bone mass. Prior dieting may be responsible. Chronic dieters should be encouraged
      to decrease their dietary restraint, develop healthy eating habits and increase
      physical activity.

PMID- 15164119
TI  - Ultrasonographic gastric emptying in protein energy malnutrition: effect of type
      of meal and nutritional recovery.
AB  - OBJECTIVE AND DESIGN: The earlier reports of disturbed gastric motility in
      protein energy malnutrition (PEM) point out to its possible contribution in the
      difficulties faced during nutritional rehabilitation. This study was thus
      designed to assess the ultrasonographic gastric emptying time (GET) using 20
      ml/kg body weight of both liquid and semisolid meals, in 27 patients suffering
      from PEM as well as in 15 healthy matching infants to delineate any defect
      present, its degree in different types of PEM and the effect of nutritional
      rehabilitation. PATIENTS: The patients were recruited from the in-patient
      department of Children's Hospital, Ain Shams University, Cairo, Egypt. They were
      divided into three groups: 10 marasmic infants, 10 marasmic kwashiorkor (marasmic
      KWO) and seven kwashiorkor (KWO) cases. Ultrasonographic GET assessment was
      carried out within 72 h of admission and 30+/-7 days after nutritional
      rehabilitation. RESULTS: The gastric half-emptying time T(1/2) of both liquid and
      semisolid meals was markedly prolonged in patients with marasmus and marasmic
      KWO. It was more delayed for the semisolid than the liquid meals. This delay was
      reversible after nutritional rehabilitation of the patients, indicating that it
      was secondary to the malnourished status. On the other hand, T(1/2) of both
      liquid and semisolid meals showed no statistically significant delay in the KWO
      group and nutritional rehabilitation added no further to the results. CONCLUSION:
      PEM, especially marasmus and marasmic KWO, causes a delay in GET, which is
      reversible on nutritional recovery. This must be considered during nutritional
      rehabilitation of such patients to decrease the duration of their hospitalization
      and thus decrease the morbidity in PEM.

PMID- 15164125
TI  - Introduction: the Mount Sinai Adolescent Health Center.

PMID- 15164120
TI  - Role of infiltrated leucocytes in tumour growth and spread.
AB  - Leucocytes are a major component of the tumour microenvironment. Recent studies
      have indicated that the infiltration and activity of these host cells are
      regulated by the tumour to promote its survival and progression. Through the
      production of an array of growth factors, proteases and angiogenic mediators,
      leucocytes in the tumour microenvironment promote tumour growth, angiogenesis and
      metastasis.

PMID- 15164121
TI  - Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial
      ovarian cancer.
AB  - Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen
      responsive gene that was identified in MCF-7 human breast carcinoma cell line. It
      is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune
      escape. In the present study, we examined the expression of EBAG9/RCAS1 in human
      epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse
      transcription-polymerase chain reaction (RT-PCR). A total of 90 epithelial
      ovarian cancer cases were examined immunohistochemically by means of the
      antibodies for EBAG9 and ERalpha. The correlation between EBAG9 immunoreactivity
      and clinicopathological parameters was examined. mRNA expression of EBAG9 and
      ERalpha were evaluated by RT-PCR in 22 cases. The expression for EBAG9 and
      ERalpha was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9
      immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in
      46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous
      histology (P=0.0402) and advanced disease (P=0.0206). No significant relationship
      was detected between EBAG9 immunoreactivity and overall survival (P=0.689). There
      was a highly significant correlation between EBAG9 and ER immunoreactivity
      (P<0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the
      cases that were positive for ERalpha mRNA, they were also positive for EBAG9
      mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of
      ovarian cancer cell lines, and was consistent with ERalpha expression. In
      conclusion, the wide distribution of EBAG9 and its relation to advanced disease
      suggest that this protein may play important roles in epithelial ovarian cancer.

PMID- 15164126
TI  - Fostering resilience in adolescent females.
AB  - The health of adolescent females can be compromised by new social morbidities
      resulting from high-risk behaviors. The presence of various risk factors will
      increase the chances of their becoming involved in these behaviors and decrease
      their ability to reach the milestones of this developmental age. Protective
      factors will moderate these risks. Physicians and other health care providers can
      help foster resilience in the face of adversity by developing a better
      understanding of these factors and using a multidisciplinary approach to care.

PMID- 15164127
TI  - Nutrition and eating disorders in adolescents.
AB  - Adequate nutrition is essential during adolescence, since growth and development
      during this period play key roles in achieving normal adult size and reproductive
      capacity. This article briefly reviews recommended caloric intake; the healthy
      balance of carbohydrates, fat and protein; and the appropriate dietary intake of
      iron, folic acid and calcium for the adolescent. A major potential obstacle to
      good nutrition for an adolescent is the development of an eating disorder such as
      anorexia nervosa or bulimia nervosa. Anorexia nervosa, characterized by severe
      underweight, fear of gaining weight, and low self-esteem and amenorrhea, is
      associated with many physiological and psychological complications with which the
      provider must be familiar. Similarly, bulimia nervosa, which presents with eating
      binges followed by compensatory behaviors such as vomiting, diet pill abuse and
      overexercise, may be harder to detect, but can also have devastating
      consequences, both physically and emotionally, for a young person. Both of these
      disorders are best treated by a multidisciplinary team of specialists to address
      the medical, psychological, and nutritional components of these illnesses.

PMID- 15164128
TI  - Adolescents and immunization: tips for the primary care provider.
AB  - Despite high immunization rates in this country, many adolescents do not receive
      all of the recommended vaccines. Each year, more than 3.5 million adolescents in
      the U.S. enter adulthood lacking recommended immunizations. This article will
      review the current recommendations for immunization for adolescents, including
      those for the meningococcal vaccine. The vaccine schedule is continually
      changing, and it is important that health care providers be up to date and
      utilize available resources with current information. Primary care providers
      should review and update immunization records with their adolescent patients on a
      routine basis.

PMID- 15164129
TI  - Foster children with special needs: The Children's Aid Society experience.
AB  - Children in foster care have many health needs. This article presents the model
      of the Children's Aid Society (CAS) of New York City in addressing these needs.
      In addition to their regular foster care program, CAS developed the Medical
      Foster Care (MFC) in response to the growing number of boarder babies (children
      with medical conditions who are abandoned at hospitals), and the Therapeutic
      Foster Care (TFC) for foster children with emotional and behavioral mental health
      problems. The MFC serves 145 children considered medically fragile, as evidenced
      by congenital diseases such as heart disease, renal agenesis, cerebral palsy,
      seizure disorders and mental retardation. The TFC serves 50 children with severe
      levels of emotional and behavioral symptomatology. As is indicated by the
      extensive services offered through CAS's regular foster care program, as well as
      MFC and TFC, these children require specialized treatment. In addition, systems
      of information maintenance and exchange surrounding the health care of foster
      children need to be improved. Often agencies are ill-equipped to do adequate
      background checks on these young people and as a result deliver them to foster
      care situations where their health needs are not revealed and therefore not
      addressed. Health care providers also need to stay informed on the overall
      subject of foster care, as their voices will probably be crucial in ensuring that
      the extensive needs of these children are adequately represented to government,
      medical and other service providers.

PMID- 15164131
TI  - Where the wild things are: the power and challenge of adolescent group work.
AB  - Because groups are an intrinsic part of the adolescent's life, group therapy can
      be a powerful and effective treatment modality for them. However, it poses many
      challenges to group leaders and members alike. This paper, drawing on Maurice
      Sendak's well-known and beloved picture book Where the Wild Things Are, describes
      some of the issues involved in setting up groups for adolescents as well as how
      various developmental tasks of this age group appear in the group process.
      Clinical examples are utilized to illustrate the challenges and therapeutic
      efficacy of such groups.

PMID- 15164130
TI  - Obtaining a history of sexual victimization from adolescent females seeking
      routine health care.
AB  - OBJECTIVE: To evaluate the clinical practice of direct physician inquiry of
      adolescent females during routine history taking and medical examination, with
      regard to their experience of childhood sexual abuse and/or assault. METHOD:
      During a one-year period, a female physician directly questioned 146 consecutive
      female patients, aged 12-22, who were being seen for routine medical histories
      and physical examinations, as to whether they had ever been sexually victimized.
      Patients who disclosed histories of sexual victimization were immediately
      counseled and provided with appropriate on-site mental health referrals. Follow
      up of these referrals was conducted to determine if patients complied with
      referrals to seek mental health services. RESULTS: For 141 of the 146 patients,
      the physician was unaware of a history of sexual victimization. Of these 141
      patients, thirty-two (23%) cases were identified using this clinical strategy.
      Almost all (93%) of these young women accepted referrals for on-site
      psychotherapy, and 81% kept their initial appointments for psychotherapy.
      CONCLUSIONS: The routine medical history and physical examination may be an
      appropriate setting for health care providers to accurately and comfortably
      elicit a history of sexual victimization from adolescent females, and provide
      appropriate referrals for mental health counseling.

PMID- 15164133
TI  - CHIP: new opportunities in adolescent health care delivery.
AB  - Children's Health Insurance Programs (CHIP), usually targeted to infants,
      toddlers, and school-aged children, have been expanded to include adolescents.
      Adolescents need some form of health insurance in order to access needed care.
      Moreover, programs and services that provide them with health care must be
      adolescent-friendly, adolescent-focused and adolescent-sensitive, and include
      specialized training for primary care providers. Translating this philosophy into
      a successful health care delivery program involves addressing the psychological,
      institutional and financial barriers that make it difficult for adolescents to
      access health care. Overcoming these barriers, especially the financial ones,
      requires that primary care providers advocate for teenagers and take advantage of
      resources made available for them. CHIP provides a critical opportunity for
      policy-makers and health care providers to further improve adolescent health care
      and to more fully integrate adolescents into the health care system.

PMID- 15164132
TI  - Legal and ethical issues facing adolescent health care professionals.
AB  - This article reviews the legal standards and ethical dilemmas surrounding the
      provision of care to adolescent patients. Uncertainty and ambiguity in this area
      has contributed to the underserving of the adolescent population. Usually, the
      legal right to consent to treatment resides with the adolescent's parent or legal
      guardian; however, there are many cases in which adolescents may provide their
      own consent. The determination that the adolescent is "mature" is one important
      factor. The law generally upholds a provider's determination of maturity of a
      patient. Minors also have the right to confidentiality in almost all situations
      in which they have the right to consent. The issue of confidentiality poses legal
      and ethical challenges to the provider in five discussed areas. Providers should
      be aware of the laws specific to their state, while keeping foremost the best
      interest of their patients. Providers should also encourage parental involvement
      and communication concerning treatment, while respecting adolescents' right to
      confidentiality.

PMID- 15164134
TI  - Adolescent school-based health care: a description of two sites in their 20th
      year of service.
AB  - PURPOSE: While there are currently nearly 1,400 school-based health centers
      (SBHC) nationwide, only 20% have been in operation for more than 10 years. The
      Mount Sinai Adolescent SBHC Program is now in its 20th year of service. The
      purpose of this study is to: (a) present the demographic data for 2003 high
      school SBHC medical visits, including age, sex and insurance status; (b) describe
      the current prevalence of medical and psychosocial risk factors of the students
      seen for examination; and (c) present general distributions for psychosocial risk
      factors found in 1988 archival information and note differences from current risk
      factors. METHODS: A retrospective chart review was conducted in high school A,
      whose SBHC serves students mainly interested in going to college, and in high
      school B, whose SBHC has a heterogeneous population with a large proportion of
      recent immigrants. Data collected included demographic variables as well as
      reports of risk factors such as: considering oneself to be overweight, history of
      sexual activity, history of sexually transmitted diseases, same-sex attraction,
      use of alcohol, cigarette smoking, use of marijuana, suicidal ideation and
      exposure to violence. RESULTS: For those participating from high school A
      (n=231): 78% female, mean age 15.75; asthma (17%); think oneself overweight
      (30%); family member with HIV (11%); sexually active (35%); same-sex attraction
      (3%); cigarette use (14%); marijuana use (13%); alcohol use (38%); suicide
      ideation (14%); witnessed violence (37%); and overweight and obese (33%). For
      those participating from high school B (n=241): 64% female; mean age 16; asthma
      (16%); think oneself overweight (32%); family member with HIV (9%); sexually
      active (43%); same-sex attraction (7%); cigarette use (38%); marijuana use (24%);
      alcohol use (53%); suicide ideation (23%); witnessed violence (33%); and
      overweight and obese (31%). In 1988, students at these schools reported: sexually
      active status (41%); marijuana use (13%); cocaine use (12%); alcohol use (20%);
      and sadness/depression (43%). CONCLUSIONS: While a snapshot of the risk factors
      in 2003 might indicate that sexual activity has decreased somewhat, substance
      use, as well as eating-related and AIDS-related issues have come to the
      forefront. SBHCs continue to serve students with intense medical and
      psychological needs. It remains crucial that SBHCs provide comprehensive medical
      and mental health services.

PMID- 15164135
TI  - Update in atherothrombotic disease.
AB  - Crucial advances in our understanding of the pathogenesis of atherothrombosis,
      defined as atherosclerosis and its thrombotic complications, have been achieved
      during the past two decades. The historical hypothesis of pathogenesis ("lipid
      accumulation") has evolved to integrate several factors contributing to the
      initiation and evolution of this complex disease. Endothelial dysfunction is
      considered to be the earliest event in atherogenesis. Inflammation and apoptosis
      play critical roles in its progression and onset. Tissue factor is postulated to
      be a central actor in determining plaque thrombogenicity. A hyperreactive state
      of the blood ("vulnerable blood") may be responsible for one-third of all the
      acute coronary syndromes. This review will discuss emerging concepts in the
      pathogenesis of and therapeutic approaches to atherothrombotic disease.

PMID- 15164136
TI  - Clinical quiz: parosteal lipoma.

PMID- 15164137
TI  - Hepatic and colonic perforation by an abandoned ventriculoperitoneal shunt.
AB  - We report a case of an abandoned distal limb of a ventriculoperitoneal shunt that
      resulted in hepatic as well as colonic perforation in a 12-year-old girl.
      Although it is common practice at the time of shunt revision to leave a retained
      distal catheter in the peritoneal cavity, we suggest this can result in
      perforation of solid as well as hollow viscera.

PMID- 15164138
TI  - More on Kartagener's syndrome and the contributions of Afzelius and A.K. Siewert.

PMID- 15164139
TI  - When a pregnant woman with suspected appendicitis is referred for a CT scan, what
      should a radiologist do to minimize potential radiation risks?

PMID- 15164140
TI  - Bilateral adrenal cystic neuroblastoma with superior vena cava syndrome and
      massive intracystic haemorrhage.
AB  - Bilateral cystic adrenal tumours are a rare presentation of neuroblastoma.
      Intratumoural haemorrhage is a frequent finding in neuroblastoma, but is rarely
      symptomatic. We present an 11-month-old girl with predominantly cystic bilateral
      neuroblastomas and distant lymph-node metastasis. Massive intracystic haemorrhage
      and superior vena cava (SVC) syndrome were ominous prognostic factors, leading to
      death. Large tumours with intracystic haemorrhage might require a conservative
      approach.

PMID- 15164141
TI  - Urinary bladder volume and pressure at reflux as prognostic factors of
      vesicoureteral reflux outcome.
AB  - BACKGROUND: Controversy exists as to whether the outcome of vesicoureteral reflux
      (VUR) can be prognosticated by direct radionuclide cystography (DRC). OBJECTIVE:
      To correlate the quantitative data obtained by DRC with disease outcome in
      infants with VUR and positive DRC 1 year after diagnosis. MATERIALS AND METHODS:
      The medical records of 109 children with known primary VUR diagnosed during the
      first year of life were studied retrospectively. One year after diagnosis all
      patients underwent DRC. Children with a positive first DRC were followed up for
      the next 36 months. Fisher's exact test was used to calculate the statistical
      significance of differences in the number of ureters with resolved reflux, as
      related to quantitative data obtained during the first DRC. RESULTS: The first
      DRC, performed 1 year after the initial diagnosis, was positive in 49 children
      (26 with bilateral reflux). Quantitative data derived from this first examination
      could not establish any prognostic value for a refluxing volume of <2% of the
      total vesical volume or a reflux at a bladder volume of more than 60% of total
      bladder capacity. When this limit was lowered to 45%, a statistically significant
      difference was found ( P=0.046). Moreover, when a bladder pressure at the time of
      reflux of more than 20 cm H(2)O was set as a criterion, an extremely significant
      probability value was calculated ( P=0.0009). CONCLUSIONS: VUR occurring at a
      bladder pressure of less than 20 cm H(2)O and a filling volume of less than 45%
      of the total bladder volume indicate a low probability for VUR resolution within
      the subsequent 36 months, in infants with known reflux.

PMID- 15164142
TI  - Ultrasound diagnosis of infantile scrotal emphysema.
AB  - We report a 4-month-old boy who developed scrotal emphysema following removal of
      a chest drain. The initial diagnosis was made by ultrasonography. This report
      describes the sonographic findings, pathophysiological mechanisms and outcome of
      this rare entity.

PMID- 15164143
TI  - A case of sporadic infantile histiocytoid cardiomyopathy caused by the A8344G
      (MERRF) mitochondrial DNA mutation.
AB  - The A8344G mitochondrial DNA (mtDNA) mutation is best known for the MERRF
      phenotype (myoclonic epilepsy, myopathy, and ragged red fibers). We describe a
      sporadic case of an infant with the A8344G mtDNA mutation who presented with
      failure to thrive and sudden unexpected death at 11 months of age. The autopsy
      revealed a histiocytoid cardiomyopathy, diffuse steatosis of the liver, and
      bilateral retinal hypoplasia. Electron micrographs of cardiac myocytes showed
      striking mitochondrial hyperplasia, dispersing the sarcomeres. Special stains of
      frozen heart muscle showed an absence of complex IV (cytochrome c oxidase) in
      many of the myocytes. Both complexes I and IV of the respiratory chain were
      reduced in cardiac muscle. The A8344G mtDNA mutation was detected in both liver
      and cardiac muscle tissue. To our knowledge, this is the first description of the
      A8344G mtDNA mutation presenting as a sporadic case of fatal infantile
      cardiomyopathy and the first occurrence of this mutation associated with
      histiocytoid cardiomyopathy.

PMID- 15164147
TI  - Effects of doxycycline on mechanical properties of bones in rats with ovariectomy
      induced osteopenia.
AB  - Tetracyclines have been reported to inhibit bone resorption and intensify bone
      formation. The aim of the present study was to investigate the effects of
      doxycycline (20 mg/kg PO daily for 28 days) on bone mechanical properties in
      bilaterally ovariectomized and sham-operated rats. The experiment was carried out
      on 3-month-old Wistar rats. Mechanical properties of the whole femur (extrinsic
      stiffness, ultimate and breaking load, deformation caused by applied load) and
      the femoral neck (load at fracture) as well as bone mass and bone mineral content
      in the tibia, femur, and L4 vertebra were examined. Bilateral ovariectomy
      resulted in decreases in bone mineral content/bone mass ratio and worsening of
      mechanical properties of the femoral neck. The changes were counteracted by
      doxycycline. Doxycycline reversed the effect of ovariectomy on load at fracture
      of the femoral neck. Doxycycline did not significantly affect the mechanical
      properties of bones in the sham-operated rats.

PMID- 15164145
TI  - Polymorphism of angiotensin-1 converting enzyme gene and Kawasaki disease.
AB  - Kawasaki disease is an acute febrile illness typically elicited by vasculitis and
      occurring in young children. We investigated the polymorphism of the angiotensin
      1 converting enzyme (ACE) gene in children with Kawasaki disease and also in age
      matched controls. A total of 107 children, with a mean age at diagnosis of 1.71
      +/- 1.48 years, who suffered from Kawasaki disease and who were treated with
      aspirin as well as intravenous immunoglobulin were enrolled in this study.
      Control subjects consisted of 107 children, with a mean age of 1.84 +/- 1.20
      years. The polymorphisms of the ACE gene, including I/D, A-240T, and G2350A, were
      examined using a polymerase chain reaction method for Kawasaki disease patients
      and also for control subjects. We noted a significant difference in the
      distribution of the ACE gene I/D genotype between Kawasaki disease and control
      groups. The ACE gene G2350A polymorphism and associated allelic frequencies
      demonstrated an association with Kawasaki disease. Our results revealed no
      evidence of any association between the ACE gene polymorphism and the frequency
      of coronary artery aneurysm associated with Kawasaki disease, although our
      results do support a role for the I/D and G2350A polymorphism of the ACE gene in
      determining the risk of Kawasaki disease in the population of Taiwan.

PMID- 15164149
TI  - Mineralization of decalcified bone occurs under cell culture conditions and
      requires bovine serum but not cells.
AB  - The purpose of this study was to develop an in vitro model system for bone matrix
      mineralization in the absence of cells. For this model, we utilized EDTA
      decalcified new-born rat tibias with the cartilaginous ends intact, allowing us
      to visually determine the specificity of mineralization within the bone. Our
      results show that supplementation of DMEM culture medium with 10mM beta
      glycerophosphate and 15% fetal bovine serum (FBS) results in non-physiological
      mineral percipitation in the tibia because of the generation of
      supraphysiological (5mM) levels of inorganic phosphate in the medium. The same
      medium supplemented only with inorganic phosphate to a final concentration of 2mM
      failed to mineralize a decalcified tibia matrix. However, additional
      supplementation of this medium with as little as 5% FBS resulted in
      mineralization of those regions of the type I collagen where mineral was found
      prior to decalcification, with no evidence for mineralization in the cartilage at
      the bone ends or in the periosteum. Analysis of the mineral by Fourier-transform
      infrared spectroscopy and powder X-ray diffraction shows that tibias that have
      been decalcified and then remineralized contain an apatitic mineral that is
      strikingly similar to the mineral in normal bone. Tendon, a type I collagen
      matrix not normally mineralized in vivo, also mineralizes when incubated in DMEM
      containing 2mM Pi and as little as 1.5% FBS, but not when incubated in DMEM
      without serum. These data indicate that serum contains a nucleator of type I
      collagen matrix mineralization, and that mineralization of type I collagen under
      cell culture conditions requires serum but not living cells.

PMID- 15164148
TI  - Fructooligosaccharides maximize bone-sparing effects of soy isoflavone-enriched
      diet in the ovariectomized rat.
AB  - Isoflavones (IF) have been increasingly implicated for use in the prevention of
      osteoporosis. As their bioavailability could be improved by modulating intestinal
      microflora, the present study was undertaken to investigate whether IF and
      fructooligosaccharides (FOS), which are known to modify large-bowel flora and
      metabolism, may exhibit a cooperative bone-sparing effect. This work was carried
      out on 3-month-old Wistar rats assigned to 12 groups: 2 SH (sham-operated) and 10
      OVX (ovariectomized). Animals received a diet for 90 days containing total IF
      (Prevastei HC, Central Soya) at 0 (OVX and SH), 10 (IF10), 20 (IF20), 40 (IF40),
      or 80 (IF80) microg/g body weight per day. FOS (Actilight, Beghin-Meiji) were
      orally given to half of the groups, (OVX FOS), (IF10 FOS), (IF20 FOS), (IF40
      FOS), (IF80 FOS), and (SH FOS). Isoflavones exhibited a bone-sparing effect as
      soon as consumption reached 20 microg/g/day, whereas only the highest dose
      induced a weak uterotrophic activity. Indeed, total femoral bone mineral density
      (BMD) was significantly enhanced (compared with that of OVX rats), as was the
      metaphyseal compartment. Bone strength was improved as well. As far as the FOS
      diet is concerned, addition of prebiotics significantly raised the efficiency of
      the IF protective effect on both femoral BMD and mechanical properties. The trend
      toward higher BMD levels with the lowest IF dose (IF10) even reached a
      significant level when FOS were added. This effect could be explained by a
      reduced bone resorption. In conclusion, daily IF consumption prevented castration
      induced osteopenia by decreasing bone resorption when given at 20, 40, or 80
      microg (total isoflavones)/g/day. Simultaneous FOS consumption improved IF
      protective effect on the skeleton, with the lowest IF dose becoming efficient.
      Enhancement of IF bioavailability, following FOS fermentation, is probably
      involved.

PMID- 15164150
TI  - Evaluation of the role of the SQSTM1 gene in sporadic Belgian patients with
      Paget's disease.
AB  - A positional cloning effort in French Canadian families with Paget's disease of
      bone (PDB) resulted in the identification of a mutation in the sequestosome1
      (SQSTM1) gene in a subset of both familial and sporadic PDB cases. This was
      confirmed in samples of mainly United Kingdom (UK) origin. In this study, we
      performed both mutation analysis and association studies in order to evaluate the
      role of this gene in a collection of isolated Belgian PDB patients. A mutation in
      the SQSTM1 gene was found in only 6 of 111 patients (5.4%). In all cases it
      involves the P392L mutation, previously shown to be common in both familial and
      sporadic cases. To perform association studies, we selected 8 single nucleotide
      polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these.
      Haplotype analysis indicated that typing of 3 Tag SNPs (IVS1 + 633A/C, IVS5 -
      23A/G, and 976A/G) enables us to identify the most common haplotypes. Association
      studies for the 3 selected SNPs, based on 105 PDB cases without a SQSTM1 mutation
      and 159 control individuals, did not support a possible influence of natural
      variants in the SQSTM1 gene either on the pathogenesis of PDB or on the disease
      severity. In conclusion, our study confirms that the P392L mutation is a
      recurrent mutation causing PDB in different populations. We were not able to show
      an association between SQSTM1 polymorphisms and PDB in our population but this
      clearly needs to be extended to other populations. The presented identification
      of haplotype Tag SNPs will be of major help for such studies.

PMID- 15164151
TI  - Recovery of the locomotor function after prolonged microgravity exposure. I. Head
      trunk movement and locomotor equilibrium during various tasks.
AB  - Recovery of locomotor function was investigated in seven cosmonauts exposed to
      microgravity for 6 months. Crew members executed a locomotor task with visual
      cues (eyes open, EO) and without them (eyes closed, EC). The locomotor task
      consisted of ascending a two-step staircase, jumping down from a 30-cm high
      platform, and finally walking 4 m in the straight-ahead direction. Subjects were
      tested before the flight (D-30), and on the second day (R+2) and the sixth day
      (R+6) after the flight. Cosmonauts succeeded in all locomotor sub-tasks as early
      as R+2. In particular, microgravity exposure did not prevent cosmonauts from
      producing a straight walking trajectory even when blindfolded (deviation at R+2
      with EO 2.0+/-0.7 degrees, and with EC 4.7+/-1.9 degrees ). However, lateral
      movements of trunk were found to be increased at R+2 (16%), suggesting post
      flight gait instability. Modifications of the timing of forward trunk movements
      were also detected at R+2. Unexpectedly, coordination patterns between head and
      trunk movements remained unchanged. The maximum amplitude of head pitches was 5
      degrees or less. Yet, the cosmonauts held their heads at lower positions at R+2
      in comparison with their pre-flight postures, and they lowered their heads even
      further during blindfolded locomotion. In general, comparable spatial and
      temporal modifications of head and trunk movements at R+2 were observed during
      the stair and gait cycles. Mean values of locomotor descriptors measured at R+6
      did not deviate from the pre-flight baseline. When performing jumps after the
      return from their flight, cosmonauts decreased the amplitude and speed of head
      rotation by approximately 50% in comparison with the pre-flight values. In
      addition, the timing of head pitches was uncertain after weightlessness. All the
      above changes endured at R+6. Previous studies reported that prolonged exposure
      to microgravity adversely affects the motor performance in the initial hours upon
      re-entry to Earth. However, gait analysis revealed that cosmonauts recovered near
      optimal locomotor abilities as early as the second day post-flight. Results
      suggest a notable capability of the central nervous system to rapidly accommodate
      to changing physical environment and body properties. The role of head
      stabilization at a lower position is conjectured to be an adaptive response to
      microgravity-induced motor disorders.

PMID- 15164152
TI  - When two eyes are better than one in prehension: monocular viewing and end-point
      variance.
AB  - Previous research has suggested that binocular vision plays an important role in
      prehension. It has been shown that removing binocular vision affects (negatively)
      both the planning and on-line control of prehension. It has been suggested that
      the adverse impact of removing binocular vision is because monocular viewing
      results in an underestimation of target distance in visuomotor tasks. This
      suggestion is based on the observation that the kinematics of prehension are
      altered when viewing monocularly. We argue that it is not possible to draw
      unambiguous conclusions regarding the accuracy of distance perception from these
      data. In experiment 1, we found data that contradict the idea that a consistent
      visuomotor underestimation of target distance is an inevitable consequence of
      monocular viewing. Our data did show, however, that positional variance increases
      under monocular viewing. We provide an alternative explanation for the kinematic
      changes found when binocular vision is removed. Our account is based on the
      changes in movement kinematics that occur when end-point variance is altered
      following the removal of binocular vision. We suggest that the removal of
      binocular vision leads to greater perceptual uncertainty (e.g. less precise
      stimulus cues), resulting in changes in the kinematics of the movement (longer
      duration movements). Our alternative account reconciles some differences within
      the research literature. We conducted a series of experiments to explore further
      the issue of when binocular information is advantageous in prehension. Three
      subsequent experiments were employed which varied binocular/monocular viewing in
      selectively lit conditions. Experiment 2 explored the differences in prehension
      measured between monocular and binocular viewing in a full cue environment with a
      continuous view of the target object. Experiment 3 required participants to
      reach, under a monocular or binocular view, for a continuously visible self
      illuminated target object in an otherwise dark room. In Experiment 3, the
      participant could neither see the target object nor the reaching hand following
      initiation of the prehension movement. Our results suggest that binocular vision
      contributes to prehension by providing additional information (cues) to the
      nervous system. These cues appear to be weighted differentially according to the
      particular constellation of stimulus cues available to the participants when
      reaching to grasp. One constant advantage of a binocular view appears to be the
      provision of on-line information regarding the position of the hand relative to
      the target. In reduced cue conditions (i.e. where a view of the target object is
      lost following initiation of the movement), binocular information regarding
      target location appears to be particularly useful in the initial programming of
      reach distance. Our results are a step towards establishing the specific
      contributions that binocular vision makes to the control of prehension.

PMID- 15164153
TI  - Phosphene threshold as a function of contrast of external visual stimuli.
AB  - Transcranial magnetic stimulation (TMS) of the occipital lobe is frequently used
      to induce visual percepts by direct stimulation of visual cortex. The threshold
      magnetic field strength necessary to elicit a visual percept is often regarded as
      a measure of electrical excitability of visual cortex. Using single-pulse TMS
      during visual motion stimulus presentation, we investigated the relationship
      between different degrees of visual cortical preactivation and cortical phosphene
      threshold (PT). The two possible, mutually exclusive, predictions on the outcome
      of this experiment were that a) PT increases with stronger preactivation because
      of a decrease in the signal-to-noise ratio, or b) that PT decreases with
      increased preactivation because of the increase in neuronal response towards some
      threshold. PTs for single-pulse stimulation of the occipital lobe were determined
      for eight subjects while they passively viewed a horizontally drifting luminance
      modulated sinewave grating. Gratings used were of four different luminance
      contrasts while the spatial and temporal frequencies remained constant. PTs were
      shown to increase significantly as the background grating increased in contrast.
      These results suggest that the neural activity underlying the perception of a
      phosphene can be considered a type of signal that can be partially masked by
      another signal, in this case the visual cortical activation produced by passive
      viewing of drifting gratings.

PMID- 15164154
TI  - Simultaneous determination of chlorophyll a and chlorophyll b by derivative
      spectrophotometry.
AB  - Chlorophyll a (Chl a) and chlorophyll b (Chl b) plant pigments, which are
      important in the food industry and are beneficial as environmental pollution
      indicators, have been extracted with a novel solvent mixture (1:1 v/v acetone
      propanol) not containing chloroform and simultaneously determined by first
      derivative spectrophotometry. The results were statistically compared to those
      obtained by the ordinary absorption spectrophotometric reference utilizing the
      principle of additivity of absorbances. The testing of the developed method in
      synthetic mixtures of Chl a and Chl b and in real plant material samples (grass,
      spinach, chard, purslane, black cabbage, crisp lettuce, rocket, dill and seaweed)
      proved successful in that the developed extractive derivative spectrophotometric
      method was both rapid and precise, and was not dependent on the Chl a/b ratio in
      contrast to the reference method which was adversely affected by the latter
      parameter.

PMID- 15164155
TI  - An improved transmutation method for quantitative determination of the components
      in multicomponent overlapping chromatograms.
AB  - An improved method is proposed for the quantitative determination of
      multicomponent overlapping chromatograms based on a known transmutation method.
      To overcome the main limitation of the transmutation method caused by the
      oscillation generated in the transmutation process, two techniques--wavelet
      transform smoothing and the cubic spline interpolation for reducing data points-
      were adopted, and a new criterion was also developed. By using the proposed
      algorithm, the oscillation can be suppressed effectively, and quantitative
      determination of the components in both the simulated and experimental
      overlapping chromatograms is successfully obtained.

PMID- 15164156
TI  - An extinction cue reduces spontaneous recovery of ataxic ethanol tolerance in
      rats.
AB  - RATIONALE AND OBJECTIVES: Ethanol ataxia experiments with rats investigated cue
      effects on conditioned tolerance. Spontaneous recovery (SR) was assessed 1 day
      and 18 days after extinction with conditioned stimuli (CSs) paired or unpaired
      with an ethanol unconditioned stimulus (US). Behavioral tolerance was assessed by
      not tilting the apparatus during conditioning. Non-associative processes were
      assessed post-conditioning with or without a buzzer cue. Bouton's (1993, Psychol
      Bull 114:80-99) memory theory was tested using an extinction cue and an
      associatively neutral cue presented during SR testing. METHODS: Tolerance was
      conditioned to a room + strobelight CS by ethanol injections experienced on a
      tilting floor (standard conditioning). Controls received no ethanol or ethanol,
      either during the CS without the floor tilting or 11 h post-CS. SR testing
      occurred 1 day or 18 days after extinction (experiment 1). Conditioning was
      followed by tolerance and CR tests either with or without a 15-s buzzer cue
      (experiment 2). In extinction, the CS and cue occurred without ethanol; the cue
      occurred before 7% or none of the extinction trials. Testing occurred 18 days
      after extinction with or without that cue (experiment 3), or with an equally
      familiar ("neutral'') cue presented before conditioning (experiment 4). RESULTS:
      Tolerance developed without floor tilting. CS-US unpairings prevented tolerance.
      Tolerance SR occurred 18 days but not 1 day after extinction only after CS-US
      pairings (experiment 1). Post-conditioning tests showed no unconditioned effects
      of the cue (experiment 2). Testing with no cue 1 day after extinction with the
      cue resulted in no tolerance increase. The extinction cue reduced SR (experiments
      3 and 4); the neutral cue did not (experiment 4). CONCLUSIONS: Cues correlated
      with extinction reduce SR. Non-associative and practice processes, Bouton's
      (1993, Psychol Bull 114:80-99) memory theory, alternative interpretations, and
      clinical implications are discussed.

PMID- 15164157
TI  - Potentiated startle and hyperalgesia during withdrawal from acute morphine:
      effects of multiple opiate exposures.
AB  - RATIONALE: Administration of an opiate antagonist following acute morphine
      exposure elevates the startle response in rodents, a phenomenon that may reflect
      the anxiogenic effects of withdrawal. Previous acute dependence studies have
      demonstrated escalated withdrawal severity following multiple withdrawal
      episodes. OBJECTIVES: To examine the effects of prior opiate exposure on the
      magnitude of withdrawal-potentiated startle and an additional measure of acute
      dependence, withdrawal-induced hyperalgesia. METHODS: The effects of repeated
      naloxone-precipitated morphine withdrawals on acoustic startle responding were
      evaluated in experiments that varied either the dose of the opiate antagonist (8
      day, repeated measures procedure) or agonist (3-day procedure). Additional
      experiments examined withdrawal-induced hyperalgesia utilizing either a single
      day dependence paradigm or the same 3-day procedure as in the startle experiment.
      RESULTS: Repeated naloxone-precipitated withdrawals from acute morphine
      exacerbated withdrawal severity in both startle procedures, although this effect
      varied biphasically (inverted-U function) with morphine dose in the 3-day
      dependence paradigm. Withdrawal from a single morphine exposure also induced
      hyperalgesia, and this effect was intensified by prior withdrawal episodes.
      CONCLUSIONS: These data demonstrate that repeated withdrawals from acute morphine
      exacerbate the severity of potentiated startle and hyperalgesia. These paradigms
      may be useful in examining the neural plasticity underlying the development of
      opiate dependence.

PMID- 15164158
TI  - The priming effect of alcohol pre-load on attentional bias to alcohol-related
      stimuli.
AB  - BACKGROUND: Previous research has shown attentional bias toward alcohol-related
      stimuli in non-dependent social drinkers. The aim of this study was to
      investigate whether attentional bias towards alcohol-related stimuli would
      increase after priming with either one of two doses of alcohol (0.3 or 0.6 g/kg)
      or placebo. METHODS: Questionnaires were used to measure alcohol use, mood
      states, craving for alcohol and alcohol outcome expectancies. Attentional bias
      was assessed using a dot-probe detection task and a modified Stroop task.
      RESULTS: Mood ratings showed dose dependent increases in positive mood after the
      alcohol pre-load. In the dot-probe task, all subjects showed an attentional bias
      towards the alcohol-related stimuli over neutral stationery-related items,
      although the attentional bias was significantly positive only at the low alcohol
      dose. In addition, a negative correlation was found between the attentional bias
      under the high alcohol dose and the alcohol use questionnaire score. In the
      Stroop task, a dose related effect of alcohol was found, with subjects making
      more errors for alcohol-related words under the high alcohol dose. CONCLUSIONS:
      These data support ideas derived from the incentive learning theories of drug
      addiction. Furthermore, these data suggest that history of alcohol exposure may
      influence the priming effects of an alcohol pre-load on attentional bias.

PMID- 15164159
TI  - Effects of nefazodone on the development of experimentally induced tumors in
      stressed rodents.
AB  - RATIONALE: Anxiety and depression are commonly encountered in patients with
      cancer and constitute risk and prognostic factors for the disease. Although
      previous findings do not support an overall association between the use of
      antidepressants and higher prevalence of cancer, results for serotonin uptake
      inhibitors are not entirely reassuring. OBJECTIVES: We evaluated the effects of
      nefazodone, a serotonin and norepinephrine (NE) reuptake inhibitor and 5-HT(2A)
      receptor antagonist antidepressant, on the appearance of breast cancer induced by
      mammary tumor virus (MTV) in mice, and on the development of lung metastases in
      rats injected intravenously with Walker 256 (W-256) carcinosarcoma cells.
      METHODS: Female C3H/He mice carrying the MTV were monitored for mammary tumor
      incidence and latent periods while being treated with a daily intraperitoneal
      injection with placebo or nefazodone. Rats were administered 10(4) W-256 cells,
      exposed to a chronic auditory stressor for 8 days, and then killed to evaluate
      metastatic nodules in the lungs. RESULTS: Although all of the mice were potential
      candidates for MTV-induced breast cancer, those treated with nefazodone were
      partially protected against adverse effects of stress induced by the daily
      administration of placebo on both parameters. Relative to placebo, nefazodone
      reduced the stress-induced increase in the number and percentage area of
      metastases in the frontal section through pulmonary hilus and increased the
      survival periods of rats given W-256 cells and exposed to a chronic auditory
      stressor. CONCLUSIONS: Our results provide evidence of the beneficial effects of
      nefazodone against the adverse effects of stress on tumor development and
      metastaticity in rodents, but did not show significant effects in unstressed
      rodents.

PMID- 15164160
TI  - Tests of linkage and/or association of TGF-beta1 and COL1A1 genes with bone mass.
AB  - Transforming growth factor beta 1 (TGF-beta1) is involved in bone metabolism and
      collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix.
      Both have been considered as candidate genes for osteoporosis. In this study, we
      employed the transmission disequilibrium test (TDT) to examine the relationship
      between each of the two genes with bone mineral density (BMD) and bone mineral
      content (BMC) at the spine and hip in a sample of 1668 subjects from 387
      Caucasian nuclear families. For the TGF-beta1 gene, three SNPs, SNP1, SNP2, and
      SNP4 (located in exon 1, intron 4 and intron 5, respectively) were tested and the
      minor allele frequencies were 30.9%, 2.1% and 27.0%, respectively. All eight
      possible haplotypes (TGF1-8) were observed. For the COL1A1 gene, the minor allele
      frequencies of SNP5, SNP6 and SNP8 (located in exon 1, intron 1, and exon 45,
      respectively) were 15.2%, 18.7%, 2.0%, respectively, and only six of eight
      potential haplotypes (COL1-6) were obtained. In the whole sample, total
      associations were observed between haplotype COL5 with spine BMD (P=0.027),
      haplotypes COL3 and TGF4 with hip BMC (P=0.002, 0.003, respectively). Within
      family associations were found for spine BMD at haplotypes TGF4 (P=0.027) in
      female offspring families and TGF3 (P=0.021) in male offspring families. Further
      studies with denser markers and larger sample size are required to eventually
      define the relationship between these two genes with bone mass at the spine and
      hip.

PMID- 15164161
TI  - The clinical significance of serum osteocalcin and N-terminal propeptide of type
      I collagen in predialysis patients with chronic renal failure.
AB  - Several new serum markers for bone metabolism have recently become available and
      are being applied to clinical practice. Their clinical usefulness in predialysis
      patients with chronic renal failure (CRF), however, has not yet been determined.
      Serum levels of three bone formation markers-bone alkaline phosphatase (BAP),
      osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)-and three
      bone resorption markers-type I collagen cross-linked N-telopeptide (NTx),
      deoxypyridinoline (DPD), and pyridinoline (PYD)-were measured simultaneously in
      85 predialysis CRF patients (serum creatinine 3.5 +/- 1.9 mg/dl, 61.0 +/- 10.9
      years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine
      the relationships between these markers and bone mineral density (BMD) of the
      distal radius, as measured by peripheral quantitative computed tomography (pQCT).
      Trabecular BMD, which is strongly affected by bone metabolism, was significantly
      negatively correlated with each of the bone formation markers (r=-0.341,
      p=0.0016, for OC; r=-0.314, p=0.0036, for PINP; r=-0.238, p=0.0315, for BAP), but
      there was no significant correlation between BMD and any of the bone resorption
      markers. In multivariate regression analyses (adjusted by age, sex, presence of
      diabetes, glomerular filtration rate, intact parathyroid hormone, calcium,
      phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly
      associated with a decrease in BMD, but BAP was not. In conclusion, we
      demonstrated that in predialysis CRF patients, BMD of the distal radius,
      particularly of trabecular bone, is associated with serum OC and PINP levels. OC
      and PINP are suggested to be possible parameters for the clinical evaluation of
      the effect of bone metabolism on BMD.

PMID- 15164163
TI  - Experimental model of knee contracture in extension: its prevention using a sheet
      made from hyaluronic acid and carboxymethylcellulose.
AB  - Treatment once extension contracture of the knee has completed is difficult and
      costly. The most effective treatment might be the prevention of contracture,
      especially after joint injury. In order to establish an effective method for
      contracture prevention we first made an extension contracture in rabbit knees,
      then studied the effect of a sheet made from hyaluronic acid and carboxymethyl
      cellulose (HA/CMC) for the prevention of knee contracture. One hundred and twenty
      two mature male Japanese white rabbits were divided into three groups: (1) group
      B (n=42), where bony holes were made at the medial and lateral epicondyles, (2)
      group H (n=40), where HA/CMC sheets were placed on the bony holes, and (3) group
      S (n=40),where only arthrotomy was performed. All surgical procedures were
      performed on the right knees. All right knees were fixed at 45 degrees using
      external fixators; this is the maximum extension angle the rabbit is able to
      tolerate and still walk. At 1, 3, and 6 weeks after surgery, we measured the
      moment necessary to flex the knee using a special device. We defined the moment
      as flexion moment (FM). Forty four left knees were also tested as group N, not
      operated on and serving as the healthy side. In all groups, FM was increased
      parallel to the increment of flexion angle from 45 degrees to 115 degrees . At
      many flexion angles, the FM in group B was higher than those of group S at 3 and
      6 weeks. The FM in group H was significantly lower than those of group B at 85
      degrees and 95 degrees of flexion at 6 weeks after the operation. By macroscopic
      observation, the area and degree of adhesion were greater in group B than those
      of group S. In group H, adhesions around the bony hole were less evident than in
      group B at 6 weeks after the operation. By histological examination, dense
      granulation tissue was found adjacent to the bony hole in group B at 3 and 6
      weeks after the operation. In contrast, in group H the amount of granulation
      tissue was smaller at 3 and 6 weeks after the operation than those of group B.
      The usage of HA/CMC sheet should be effective for prevention of contracture
      occurring after trauma such as treatment for intra-articular fracture.

PMID- 15164162
TI  - Tendon regeneration: an anatomical and histological study in sheep.
AB  - Utilization of the hamstring tendon in reconstruction of the anterior cruciate
      ligament (ACL) has become common in recent years. In MRI studies regeneration
      potential in harvested tendon has been observed. In the present study, 20 legs
      from ten sheep, which underwent 10 cm segment resection of tendon of musculus
      extensor digitalis lateralis (MEDL) were used. The sheep were killed 6 months
      after the operation and regenerated tendons were examined macroscopically and
      histologically. Dissection was performed in the tendon resection area and
      specimens were reharvested for histological examination. Regeneration of the
      tendon with normal anatomical topographies was found in all legs. Regeneration
      occurred on both sides of the resected tendon simultaneously. Regeneration was
      muscle-like in the proximal side but it was tendon-like in the distal side. The
      developed tendon was fused to the joint capsule and to the fascia at the joint
      line in all specimens. This study indicates that tendon has a potential for
      regeneration.

PMID- 15164164
TI  - Internal fixation for osteochondritis dissecans of the knee.
AB  - Eight knees of seven patients with osteochondritis dissecans of the knee
      underwent internal fixation of the fragments. The affected location was the
      medial femoral condyle in four knees, the lateral femoral condyle in one knee and
      the patellar groove in three knees. At the time of surgery, patient age ranged
      from 13 to 20 years (mean 16.9 years). Open reduction and internal fixation of
      the unstable fragments was performed with autologous bone pegs in one knee. In
      the other seven knees, the procedures were carried out with biodegradable poly-L
      lactide pins. At a mean follow-up of 5 years (range 4-6.8 years), seven fragments
      were united, whereas one knee required arthroscopic removal of the loose
      fragment. Neither effusion nor synovitis was noticed in any of the patients
      treated with biodegradable pins. The technique is simple and provides
      satisfactory results, suggesting a valid option for the treatment of
      osteochondral defects where possible.

PMID- 15164165
TI  - Knee arthrodesis using circular external fixator in the treatment of infected
      knee prosthesis: case report.
AB  - A patient (68 years old and male) underwent total knee replacement because of
      arthrosis, but he subsequently had infection due to a wound problem. Although he
      underwent early debridement, antibiotherapy, and soft-tissue operation, treatment
      failed because of improper soft-tissue coverage and progression of the infection.
      Therefore, the prosthesis was removed and a spacer with antibiotic was placed, in
      order to provide soft-tissue coverage and to eradicate infection. After 2 months,
      the patient underwent knee arthrodesis using a circular external fixator to
      achieve a stable lower extremity and to facilitate return to activities of daily
      living. We obtained knee fusion at 4 months without any requirement for secondary
      procedure of soft tissue and bone graft. There was no major complication.
      Arthrodesis with circular external fixator is a reliable and successive method
      that should be preferred for the treatment of infected knee replacement.

PMID- 15164166
TI  - Evaluation of left ventricular performance: an insolvable problem in human
      beings? The Graal quest.

PMID- 15164168
TI  - Potent activation of multiple signalling pathways by C-peptide in opossum kidney
      proximal tubular cells.
AB  - AIMS/HYPOTHESIS: Proinsulin C-peptide is generally believed to be inert without
      any appreciable biological functions. However, it has been shown to modulate a
      variety of cellular processes important in the pathophysiology of diabetic
      complications. We therefore investigated the ability of C-peptide to stimulate
      intracellular signalling pathways in kidney proximal tubular cells, the altered
      activation of which may possibly be related to the development of diabetic
      nephropathy. METHODS: Extracellular signal-regulated kinase (ERK) and Akt
      phosphorylation were evaluated by western blotting. ERK activity was measured by
      in vitro kinase assay. Intracellular Ca(2+) was evaluated by confocal imaging.
      The membrane and cytosol-associated fractions of protein kinase C (PKC) isoforms
      were evaluated by western blotting. Proliferation was assessed by thymidine
      incorporation assay. RESULTS: Using the opossum proximal tubular kidney cell line
      as a model, we demonstrated that at high picomolar to low nanomolar
      concentrations, C-peptide stimulates extracellular signal-regulated mitogen
      activated kinase (3.3+/-0.1-fold over basal at 3 minutes) and
      phosphatidylinositol 3-kinase (4.1+/-0.05-fold over basal at 5 minutes). ERK
      activation was attenuated by pre-treatment with a PKC inhibitor and abolished by
      pertussis toxin. Elevations of intracellular [Ca(2+)] are seen in response to 5
      nmol/l C-peptide with consequent activation of PKC-alpha. Pre-treatment with
      pertussis toxin abolished PKC-alpha. C-peptide is also a functional mitogen in
      this cell type, stimulating significantly increased cell proliferation.
      Proliferation was attenuated by wortmannin and pertussis toxin pre-treatments.
      None of these effects is reproduced by scrambled C-peptide.
      CONCLUSIONS/INTERPRETATION: This study provides evidence that C-peptide, within
      physiological concentration ranges, stimulates many signalling pathways in
      opossum kidney cells.

PMID- 15164169
TI  - Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular
      disease in subjects with impaired glucose tolerance: facts and interpretations
      concerning the critical analysis of the STOP-NIDDM Trial data.
AB  - The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired
      glucose tolerance is associated with a significant risk reduction in the
      development of diabetes, hypertension and cardiovascular complications. Kaiser
      and Sawicki have accused the investigators of the STOP-NIDDM Trial of major
      biases in the conduct of the study, of manipulating the data and of conflict of
      interest. The aim of this paper is to present data and explanations refuting
      these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the
      efficacy analysis before unblinding for legitimate reasons: failure to satisfy
      major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding
      and randomisation were carried out by an independent biostatistician. Titration
      of placebo/acarbose is well described in the protocol and in the study design
      paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0
      mmol/l at screening and could have been diabetic according to the new diagnostic
      criteria. However, even if these subjects are excluded, patients having acarbose
      treatment still saw a significant risk reduction in the development of diabetes
      (p=0.0027). The changes in weight are consistent in different publications and
      are related to different times of follow-up and assessment. Weight change does
      have an effect on the development of diabetes, but acarbose treatment is still
      effective even after adjusting for this (p=0.0063). The cardiovascular endpoints
      were a clearly designated assessment in the original protocol, and only those
      defined in the protocol and ascertained by the independent Cardiovascular Event
      Adjudication Committee were used in the analysis. Hypertension was defined
      according to the most recent diagnostic criteria. The STOP-NIDDM Trial results
      are scientifically sound and credible. The investigators stand strongly behind
      these results demonstrating that acarbose treatment is associated with a delay in
      the development of diabetes, hypertension and cardiovascular complications in a
      high-risk population with IGT.

PMID- 15164170
TI  - Nerve growth factor promotes reparative angiogenesis and inhibits endothelial
      apoptosis in cutaneous wounds of Type 1 diabetic mice.
AB  - AIMS/HYPOTHESIS: The neurotrophin nerve growth factor (NGF) is pro-angiogenic and
      facilitates wound repair. The present study was conducted to (i) assess the
      statement of NGF system components in diabetic wounds and (ii) evaluate whether
      NGF supplementation could prevent impairment of wound neoangiogenesis by
      diabetes. METHODS: Skin wounds were produced in the interscapular region of
      streptozotocin-induced diabetic mice. NGF (1 microg per day in PBS) or vehicle
      was applied onto the ulcers for 3 days after punching. Non-diabetic mice were
      used as controls. RESULTS: In wounds of untreated diabetic mice, endogenous
      levels of immunoreactive NGF were lower than those in wounds of non-diabetic mice
      ( p<0.01). Immunohistochemical analysis showed down-regulation of tyrosine kinase
      receptor-A (TrkA) and up-regulation of p75 receptor in granulation tissue
      microvasculature. Local NFG administration prevented diabetes-induced
      expressional alterations, enhanced reparative capillarisation ( p<0.01), and
      accelerated wound closure ( p<0.01). This was associated with a three-fold
      increase in endothelial cell proliferation ( p<0.01), while apoptosis was reduced
      by 50% ( p<0.05). Quantitative RT-PCR documented a 5.5-fold increase in the
      expression of vascular endothelial growth factor-A (VEGF-A) by exogenous NGF in
      diabetic tissues ( p<0.01). In in vitro preparations of human endothelial cells
      from derma, NGF increased the release of immunoreactive VEGF-A, and reduced high
      glucose-induced apoptosis ( p<0.05), the latter effect being inhibited by a VEGF
      A receptor-2 antagonist. CONCLUSIONS/INTERPRETATION: Diabetic ulcers display
      distinct alterations in reparative angiogenesis and in the expression of NGF and
      its receptors. NGF supplementation corrects endogenous liabilities, facilitates
      vascular regeneration, and suppresses endothelial apoptosis seemingly via VEGF-A.
      Our findings unravel new mechanisms responsible for NGF reparative action.

PMID- 15164171
TI  - Diabetes mellitus and risk of prostate cancer: a meta-analysis.
AB  - AIMS/HYPOTHESIS: The association of diabetes mellitus with prostate cancer has
      been controversial. This study examines the strength of this association by
      conducting a detailed meta-analysis of the studies published in peer-reviewed
      literature on the subject. METHODS: A comprehensive search for articles published
      up to 2003 was performed, reviews of each study were conducted and data were
      abstracted. Prior to meta-analysis, the studies were evaluated for publication
      bias and heterogeneity. Pooled relative risk (RR) was calculated using the random
      and the fixed-effects models. Subgroup and sensitivity analyses were also
      performed. RESULTS: We included 14 studies, published between 1971 and 2002, in
      the meta-analysis (five case-control studies, nine cohort studies). We found no
      evidence of publication bias ( p=0.89) or heterogeneity among the studies (
      p=0.38). The association of diabetes with prostate cancer was statistically
      significant, both on the basis of a random-effects model (RR=0.91, 95% CI: 0.86
      to 0.96), and on the basis of a fixed-effects model (RR=0.91, 95% CI: 0.88 to
      0.94). When the analysis was stratified into subgroups according to study design,
      the association was inverse in both cohort and case-control studies, but only in
      the former was it statistically significant. The sensitivity analysis
      strengthened our confidence in the validity of this association.
      CONCLUSIONS/INTERPRETATION: Our meta-analysis findings provide strong evidence
      that people with diabetes have a significant decrease in risk of developing
      prostate cancer. There is biological evidence to support this association.

PMID- 15164173
TI  - SSR marker and ITS cleaved amplified polymorphic sequence analysis of soybean x
      Glycine tomentella intersubgeneric derived lines.
AB  - Wild perennial Glycine species are an invaluable gene resource for the cultivated
      soybean [ Glycine max (L.) Merr., 2 n=40]. However, these wild species have been
      largely unexplored in soybean breeding programs because of their extremely low
      crossability with soybean and the need to employ in vitro embryo rescue methods
      to produce F(1) hybrids. The objective of this study was to develop molecular
      markers to identify gene introgression from G. tomentella, a wild perennial
      Glycine species, to soybean. A selection of 96 soybean simple sequence repeat
      (SSR) markers was evaluated for cross-specific amplification and polymorphism in
      G. tomentella. Thirty-two SSR markers (33%) revealed specific alleles for G.
      tomentella PI 483218 (2 n=78). These SSR markers were further examined with an
      amphidiploid line (2 n=118) and monosomic alien addition lines (MAALs), each with
      2 n=40 chromosomes from soybean and one from G. tomentella. The results show that
      the use of SSR markers is a rapid and reliable method to detect G. tomentella
      chromosomes in MAALs. We also developed a cleaved amplification polymorphism
      sequence (CAPS) marker according to the sequences of internal transcribed spacer
      (ITS) regions in soybean and G. tomentella. Four MAALs that carry the ITS (rDNA)
      locus from G. tomentella were identified. The SSR and ITS-CAPS markers will
      greatly facilitate the introgression and characterization of gene transfer from
      G. tomentella to soybean.

PMID- 15164172
TI  - Enhanced insulin secretion and cholesterol metabolism in congenic strains of the
      spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent
      genetic loci in rat chromosome 8.
AB  - AIMS/HYPOTHESIS: Genetic investigations in the spontaneously diabetic (Type 2)
      Goto Kakizaki (GK) rat have identified quantitative trait loci (QTL) for diabetes
      related phenotypes. The aims of this study were to refine the chromosomal mapping
      of a QTL ( Nidd/gk5) identified in chromosome 8 of the GK rat and to define a
      pathophysiological profile of GK gene variants underlying the QTL effects in
      congenics. METHODS: Genetic linkage analysis was carried out with chromosome 8
      markers genotyped in a GKxBN F2 intercross previously used to map diabetes QTL.
      Two congenic strains were designed to contain GK haplotypes in the region of
      Nidd/gk5 transferred onto a Brown Norway (BN) genetic background, and a broad
      spectrum of diabetes phenotypes were characterised in the animals. RESULTS:
      Results from QTL mapping suggest that variations in glucose-stimulated insulin
      secretion in vivo, and in body weight are controlled by different chromosome 8
      loci (LOD3.53; p=0.0004 and LOD4.19; p=0.00007, respectively). Extensive
      physiological screening in male and female congenics at 12 and 24 weeks revealed
      the existence of GK variants at the locus Nidd/gk5, independently responsible for
      significantly enhanced insulin secretion and increased levels of plasma
      triglycerides, phospholipids and HDL, LDL and total cholesterol. Sequence
      polymorphisms detected between the BN and GK strains in genes encoding ApoAI,
      AIV, CIII and Lipc do not account for these effects. CONCLUSIONS/INTERPRETATION:
      We refined the localisation of the QTL Nidd/gk5 and its pathophysiological
      characteristics in congenic strains derived for the locus. These congenic strains
      provide novel models for testing the contribution of a subset of GK alleles on
      diabetes phenotypes and for identifying diabetes susceptibility genes.

PMID- 15164174
TI  - Fine mapping of a malting-quality QTL complex near the chromosome 4H S telomere
      in barley.
AB  - Malting quality has long been an active objective in barley (Hordeum vulgare L.)
      breeding programs.However, it is difficult for breeders to manipulate malting
      quality traits because of inheritance complexity and difficulty in evaluation of
      these quantitative traits. Quantitative trait locus (QTL) mapping provides
      breeders a promising basis with which to manipulate quantitative trait genes. A
      malting-quality QTL complex, QTL2, was mapped previously to a 30-cM interval in
      the short-arm telomere region of barley chromosome 4H in a "Step-toe"/"Morex"
      doubled haploid population by the North American Barley Genome Project, using an
      interval mapping method with a relatively low-resolution genetic map. The QTL2
      complex has moderate effects on several malting-quality traits, including malt
      extract percentage(ME), a-amylase activity (AA), diastatic power (DP), malt 13
      glucan content (BG), and seed dormancy, which makes it a promising candidate gene
      source in malting barley-cultivar development. Fine mapping QTL2 is desirable for
      precisely studying barley malting-quality trait inheritance and for efficiently
      manipulating QTL2 in breeding. A reciprocal-substitution mapping method was
      employed to fine map QTL2. Molecular marker-assisted backcrossing was used to
      facilitate the generation of isolines. Fourteen different types of "Steptoe"
      isolines, including regenerated "Steptoe" and 13 different types of "Morex"
      isolines,including regenerated "Morex", were made within a 41.5-cM interval
      between MWG634 and BCD265B on chromosome 4H. Duplicates were identified for 12
      "Steptoe" and 12 "Morex" isoline types. The isolines together with "Steptoe" and
      "Morex" were grown variously at three locations in 2 years for a total of five
      field environments.Four malting-quality traits were measured: ME, DP, AA,and BG.
      Few significant differences were found between duplicate isolines for these
      traits. A total of 15 putative QTLs were mapped; three for ME, four for DP, six
      for AA,and two for BG. Background genotype seemed to make a difference in
      expression/detection of QTLs. Of the 15 QTLs identified, ten were from the
      "Morex" and only five from the "Steptoe" background. By combining the results
      from different years, field environments, and genetic backgrounds and taking into
      account overlapping QTLsegments, six QTLs can be conservatively estimated: two
      each for ME and AA and one each for DP and BG with chromosome segments ranging
      from 0.7 cM to 27.9 cM. A segment of 15.8 cM from the telomere (MWG634-CDO669)
      includes all or a portion of all QTLs identified. Further study and marker
      assisted breeding should focus on this 15.8-cM chromosome region.

PMID- 15164175
TI  - Characterization of low-molecular-weight glutenin genes in Aegilops tauschii.
AB  - This paper reports the characterization of the low-molecular-weight (LMW)
      glutenin gene family of Aegilops tauschii (syn. Triticum tauschii), the D-genome
      donor of hexaploid wheat. By analysis of bacterial artificial chromosome (BAC)
      clones positive for hybridization with an LMW glutenin probe, seven unique LMW
      glutenin genes were identified. These genes were sequenced, including their
      untranslated 3' and 5' flanking regions. The deduced amino acid sequences of the
      genes revealed four putative active genes and three pseudogenes. All these genes
      had a very high level of similarity to LMW glutenins characterized in hexaploid
      wheat. The predicted molecular weights of the mature proteins were between 32.2
      kDa and 39.6 kDa, and the predicted isoelectric points of the proteins were
      between 7.53 and 8.06. All the deduced proteins were of the LMW-m type. The
      organization of the seven LMW glutenin genes appears to be interspersed over at
      least several hundred kilo base pairs, as indicated by the presence of only one
      gene or pseudogene per BAC clone. Southern blot analysis of genomic DNA of Ae.
      tauschii and the BAC clones containing the seven LMW glutenin genes indicated
      that the BAC clones contained all LMW glutenin-hybridizing bands present in the
      genome. Two-dimensional gel electrophoresis of an LMW glutenin extract from Ae.
      tauschii was conducted and showed the presence of at least 11 distinct proteins.
      Further analysis indicated that some of the observed proteins were modified
      gliadins. These results suggest that the actual number of typical LMW glutenins
      may in fact be much lower than previously thought, with a number of modified
      gliadins also being present in the polymeric fraction.

PMID- 15164177
TI  - Molecular pathology of renal cell carcinoma.

PMID- 15164178
TI  - Early and late genetic changes in clear cell renal carcinoma.

PMID- 15164176
TI  - Construction and characterization of a soybean bacterial artificial chromosome
      library and use of multiple complementary libraries for genome physical mapping.
AB  - Two plant-transformation-competent large-insert binary clone bacterial artificial
      chromosome (hereafter BIBAC) libraries were previously constructed for soybean
      cv. Forrest, using BamHI or HindIII. However, they are not well suited for clone
      based genomic sequencing due to their larger ratio of vector to insert size (27.6
      kbp:125 kbp). Therefore, we developed a larger-insert bacterial artificial
      chromosome (BAC) library for the genotype in a smaller vector (pECBAC1), using
      EcoRI. The BAC library contains 38,400 clones; about 99.1% of the clones have
      inserts; the average insert size is 157 kbp; and the ratio of vector to insert
      size is much smaller (7.5 kbp:157 kbp). Colony hybridization with probes derived
      from several chloroplast and mitochondrial genes showed that 0.89% and 0.45% of
      the clones were derived from the chloroplast and mitochondrial genomes,
      respectively. Considering these data, the library represents 5.4 haploid genomes
      of soybean. The library was hybridized with six RFLP marker probes, 5S rDNA and
      18S-5.8S-25S rDNA, respectively. Each RFLP marker hybridized to about six clones,
      and the 5S and 18S-5.8S-25S rDNA probes collectively hybridized to 402 BACs-
      about 1.05% of the clones in the library. The BAC library complements the
      existing soybean Forrest BIBAC libraries by using different restriction enzymes
      and vector systems. Together, the BAC and BIBAC libraries encompass 13.2 haploid
      genomes, providing the most comprehensive clone resource for a single soybean
      genotype for public genome research. We show that the BAC library has enhanced
      the development of the soybean whole-genome physical map and use of three
      complementary BAC libraries improves genome physical mapping by fingerprint
      analysis of most of the clones of the library. The rDNA-containing clones were
      also fingerprinted to evaluate the feasibility of constructing contig maps of the
      rDNA regions. It was found that physical maps for the rDNA regions could not be
      readily constructed by fingerprint analysis, using one or two restriction
      enzymes. Additional data to fingerprints and/or different fingerprinting methods
      are needed to build contig maps for such highly tandem repetitive regions and
      thus, the physical map of the entire soybean genome.

PMID- 15164179
TI  - Current limitations of radiofrequency ablation in renal cell carcinoma.

PMID- 15164180
TI  - Cytotoxic chemotherapy for metastatic renal cell carcinoma.

PMID- 15164182
TI  - Vascular parkinsonism.
AB  - The concept of vascular parkinsonism (VP) has been highly controversial since the
      initial paper by Critchley in 1929. This review tentatively delineates the extent
      of the spectrum of VP. Much confusion has arisen owing to the lack of clear
      definitions of parkinsonism, "atypical parkinsonism" and "pseudoparkinsonism",
      which we here attempt to define. Confusion has also arisen because incidental
      vascular lesions occurring in true idiopathic Parkinson's disease (IPD) are up to
      10 times more common than parkinsonism due to cerebrovascular disease. VP is
      clinically heterogeneous. Most often VP is atypical and can be separated from
      IPD, on the basis of the presence of additional focal signs, and the absence of
      typical resting tremor in the upper limbs, of true akinesia (i. e.: with
      decrement and fatiguing of alternating movements), and of definite benefit from
      levodopa. Exceptionally, VP may mimic IPD or other degenerative diseases such as
      progressive supranuclear palsy or corticobasal degeneration. The lesions
      responsible for VP are mostly basal ganglia lacunes and/or subcortical white
      matter vasculopathy of the "Binswanger" type. Rarely, a single striatal infarct,
      striatal cribriform cavities or ischaemic changes in the substantia nigra have
      been described. Vascular "pseudo-parkinsonism" refers to isolated gait disorders
      called "lower body parkinsonism", "frontal-type gait disorders" or "gait ignition
      failure" that are reminiscent of, but distinct from, that found in IPD. The
      pathophysiology of VP is poorly understood. Why some patients develop
      parkinsonism and others do not, despite the same apparent lesion load, remains a
      mystery.

PMID- 15164181
TI  - Specific monoclonal antibody-based immunotherapy by targeting the RCC-associated
      antigen carbonic anhydrase-IX(G250/MN).

PMID- 15164183
TI  - How to treat tremor.
AB  - This paper presents an example of 18(th) century medical thinking. The author, Dr
      Georg Ernst Stahl (1659-1734) was the founder of the phlogiston theory in the
      field of chemistry, a medical professor, and a court physician in Saxony and
      Prussia. His description includes a definition of tremor, the internal and
      external causes of tremor, the types of tremor, the diagnostic and prognostic
      signs, and the treatment. From a present (contemporary) point of view, some
      compounds that were then used in treatment may have had a limited therapeutic
      effect on some kinds of tremor. Protopin has an anticholinergic and GABA-ergic
      effect, and rhoeadin (tetrahydrobenzazepin) may have had an effect similar to
      that of neuroleptics. Nevertheless, it is not clear whether the recommended
      quantity of these compounds was sufficient for a clinical effect. Most of the
      prescribed drugs could only have had a placebo effect.

PMID- 15164184
TI  - Comparison of secondary vascular prevention in practice after cerebral ischemia
      and coronary heart disease.
AB  - BACKGROUND: Secondary prevention measures in patients with cerebral ischemia or
      coronary heart disease (CHD) consist of vascular risk factors management and
      antithrombotic therapy. The aim of this study was to compare how secondary
      prevention measures are applied in practice between patients with a history of
      CHD or cerebral ischemia. METHOD: We compared vascular risk factors management
      and antithrombotic therapy between patients with a history of CHD and patients
      with a history of cerebral ischemia that occurred 2 months to 6 years earlier.
      Whether patients were properly treated or not was determined by a comparison
      between their current treatments and European guidelines for stroke and CHD
      management. RESULTS: We included 107 consecutive patients with a history of
      cerebral ischemia and 85 consecutive patients with a history of CHD. We found
      that: (i). most patients did not receive an appropriate secondary prevention in
      both groups: 76 of 107 patients with previous cerebral ischemia (71 %) and 73 of
      85 patients with CHD (85.9 %); (ii). identification of risk factors, such as
      hypercholesterolemia, diabetes mellitus and smoking, did not differ between both
      groups, but arterial hypertension was more frequent in CHD patients; (iii). an
      inappropriate management of risk factors was more frequent in patients with TIA
      vs. ischemic stroke, and angina pectoris vs. myocardial infarction; (iv).
      arterial hypertension and hypercholesterolemia were the 2 more frequent risk
      factors that were not properly treated; (v). more than half diabetic patients had
      hyperglycemia > or= 126 mg/dl in both groups; (vi). patients with previous CHD
      had twice more frequently stopped smoking than those with cerebral ischemia.
      CONCLUSION: Many patients were not properly treated in both groups, and
      differences between practice and guidelines were more frequent in the CHD group,
      where guidelines are more strict.

PMID- 15164185
TI  - Cerebral microbleeds and white matter changes in patients hospitalized with
      lacunar infarcts.
AB  - Microbleeds (MBs) detected by gradient-echo T2*-weighted MRI (GRE-T2*),white
      matter changes and lacunar infarcts may be regarded as manifestations of
      microangiopathy. The establishment of a quantitative relationship among them
      would further strengthen this hypothesis. We aimed to investigate the frequency
      and the number of MBs in patients hospitalized with lacunar infarcts and their
      quantitative relationship with the severity of white matter changes (WMC) and the
      number of old lacunar infarcts. We performed a hospital-based survey of patients
      with acute lacunar infarct. Eighty-two consecutive Chinese patients with acute
      lacunar infarcts on diffusion-weighted imaging were recruited in 2002. The number
      of MBs, number of old lacunar infarcts on T2-weighted imaging and the severity of
      WMC on MRI on admission were recorded. MBs were detected in 22 (27%) patients.
      The number of MBs ranged from 1 to 42 (mean 6.59, median 3). Advancing age and
      previous transient ischemic attacks or cerebrovascular accidents (TIA/CVA) were
      more common in patients with MBs than those without. There were significant
      correlations among the number of MBs, extent of WMC and number of lacunar
      infarcts: lacunar infarcts and MBs (r = 0.297, p = 0.007); lacunar infarct and
      WMC (r = 0.331, p = 0.002); WMC and MBs (r = 0.522, p < 0.0001). In conclusion,
      linear associations exist among MBs, WMC and lacunar infarcts. Our results
      suggest that all three may have a shared pathogenesis such as advanced
      microangiopathy.

PMID- 15164186
TI  - Increased prevalence of and gene transcription by Chlamydia pneumoniae in
      cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.
AB  - Microbial agents may play a role in the pathogenesis of multiple sclerosis (MS).
      C. pneumoniae has been recently associated with MS; however, study results are at
      variance. We tested the hypothesis that Chlamydia pneumoniae-specific DNA and RNA
      are more often detected in cerebrospinal fluid (CSF) of patients with multiple
      sclerosis than patients with other neurological diseases (OND). We investigated
      CSF samples from 84 patients with definite MS and 89 OND patients (n = 62 with
      normal CSF; n = 27 with pathological CSF) using a nested polymerase chain
      reaction (PCR) to detect ompA gene sequences of C. pneumoniae. In subjects with
      positive PCR, we probed for chlamydial heat shock protein 60-mRNA and 16S-rRNA by
      reverse transcriptase (rt)-PCR. C. pneumoniae-specific DNA was more often
      detected in MS patients (50 %) than in all OND patients combined (28.1%, p =
      0.003) and in OND patients with normal CSF (24.2%, p = 0.003) but not than in OND
      patients with pathological CSF (37%, p = 0.24). In relapsing-remitting MS (n =
      55), the prevalence of C. pneumoniae DNA was higher (66.7 %) than in both OND
      subgroups (p <or= 0.05). In MS patients (n = 20), chlamydial heat shock protein
      60-mRNA (75%) and 16S-rRNA (70%) were more often detected than in OND patients (n
      = 16; 18.8%; p < 0.005). Although more often detected in remitting-relapsing MS,
      C. pneumoniae DNA in CSF is not specific for MS owing to its high prevalence in
      OND controls. However, the higher rate of gene transcription suggests a more
      active metabolism of C. pneumoniae in MS patients.

PMID- 15164187
TI  - Uncommon findings in idiopathic hypertrophic cranial pachymeningitis.
AB  - BACKGROUND: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare,
      poorly understood, inflammatory disease, usually involving the dura mater of
      skull base, tentorium, and falx, and presenting with headache, progressive
      cranial nerve palsies, and cerebellar dysfunction. PATIENTS AND METHODS: In four
      patients, the diagnosis of IHCP has been made on the basis of extensive clinical,
      and radiological investigation, and confirmed by dural biopsy in three patients.
      The clinical follow-up ranges from 24 to 120 months. RESULTS: At diagnosis, all
      the patients complained of severe, progressively increasing headache, two had
      simple or complex partial seizures, but none had cranial nerve palsies. Two
      patients had electrophysiological evidence of axonal peripheral neuropathy,
      biopsy-proved in one of them. In all the patients, MRI showed linear or focal
      thickening of the dura mater of the tentorium and/or of the convexity, sparing
      the skull base. In one patient, MRI findings resembled chronic subdural hematoma.
      Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory
      infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the
      peripheral neuropathy. In three patients, temporary steroids withdrawal led to
      dramatic clinical worsening including status epilepticus in one. CONCLUSIONS: In
      the patients here reported, absence of cranial nerve impairment, seizures, MRI
      findings resembling chronic subdural hematoma, and association with
      polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory
      infiltrate, lacking in previous reported cases, suggests a probable pathogenetic
      role for cell-mediated immunity of unknown origin.

PMID- 15164188
TI  - Muscle computed tomography patterns in patients with the mitochondrial DNA
      mutation 3243A>G.
AB  - Computed tomography provides a sensitive method for investigating skeletal muscle
      changes in neuromuscular diseases, but this method has not been applied to
      mitochondrial myopathies. We characterized the pattern of muscle involvement in
      patients with the 3243A>G mutation in mitochondrial DNA (mtDNA), the common MELAS
      (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes) mutation. Twenty-four patients, age 19-73 years, with 3243A>G were
      examined. Clinical evaluation included assessment of muscle strength and
      functional capacity. All the patients underwent muscle computed tomography, and
      muscle samples from 17 of them were examined for the presence of ragged red
      fibres and for the 3243A>G heteroplasmy. Venous blood lactate at rest and serum
      creatine kinase were determined. Clinical myopathy was found in six patients,
      while nine showed mild muscle weakness and nine had normal muscle function. The
      upper and lower limbs were equally affected, but the proximal muscles were more
      severely affected than the distal ones. CT revealed abnormalities in the muscles
      of 13 patients (54%; 95% confidence interval, 33-76%), including the six with
      clinical myopathy and seven without clinical myopathy. Myopathic changes were
      found most frequently in the pelvic muscles, with predominant involvement of the
      gluteus maximus. These data show that CT reveals frequent abnormal findings in
      the muscle of patients with the 3243A>G mtDNA mutation. Muscle CT is a useful
      adjunct to clinical evaluation in these patients.

PMID- 15164189
TI  - Reduced cerebral blood flow velocity and impaired cerebral autoregulation in
      patients with Fabry disease.
AB  - In Fabry disease, there is glycosphingolipid storage in vascular endothelial and
      smooth muscle cells and neurons of the autonomic nervous system. Vascular or
      autonomic dysfunction is likely to compromise cerebral blood flow velocities and
      cerebral autoregulation. This study was performed to evaluate cerebral blood flow
      velocities and cerebral autoregulation in Fabry patients. In 22 Fabry patients
      and 24 controls, we monitored resting respiratory frequency, electrocardiographic
      RR-intervals, blood pressure, and cerebral blood flow velocities (CBFV) in the
      middle cerebral artery using transcranial Doppler sonography. We assessed the
      Resistance Index, Pulsatility Index, Cerebrovascular Resistance, and spectral
      powers of oscillations in RR-intervals, mean blood pressure and mean CBFV in the
      high (0.15-0.5 Hz) and sympathetically mediated low frequency (0.04-0.15 Hz)
      ranges using autoregressive analysis. Cerebral autoregulation was determined from
      the transfer function gain between the low frequency oscillations in mean blood
      pressure and mean CBFV. Mean CBFV (P < 0.05) and the powers of mean blood
      pressure (P < 0.01) and mean CBFV oscillations (P < 0.05) in the low frequency
      range were lower,while RR-intervals, Resistance Index (P < 0.01), Pulsatility
      Index, Cerebrovascular Resistance (P < 0.05), and the transfer function gain
      between low frequency oscillations in mean blood pressure and mean CBFV (P <
      0.01) were higher in patients than in controls. Mean blood pressure, respiratory
      frequency and spectral powers of RR-intervals did not differ between the two
      groups (P > 0.05). The decrease of CBFV might result from downstream stenoses of
      resistance vessels and dilatation of the insonated segment of the middle cerebral
      artery due to reduced sympathetic tone and vessel wall pathology with decreased
      elasticity. The augmented gain between blood pressure and CBFV oscillations
      indicates inability to dampen blood pressure fluctuations by cerebral
      autoregulation. Both, reduced CBFV and impaired cerebral autoregulation, are
      likely to be involved in the increased risk of stroke in patients with Fabry
      disease.

PMID- 15164190
TI  - Gait analysis of sporadic and hereditary spastic paraplegia.
AB  - OBJECTIVES: Sporadic (SSP) and hereditary spastic paraplegias (HSP) are
      clinically and genetically heterogeneous disorders, which are characterised by a
      slowly progressive spastic paraparesis. Initial symptoms and the rate of
      progression are variable even among members of the same family. Spastic
      paraparesis is the major and most disabling clinical symptom and was assessed
      with gait analysis using a three-dimensional infrared movement analysis system.
      METHODS AND RESULTS: 22 patients with clinically and/or genetically confirmed
      SSP/HSP were compared with age-matched control subjects. Significantly lower
      values were found for gait velocity, stride length, step height and the range of
      motion of the knee-angle. The gait pattern is characterised by a severe
      spasticity of both legs with only mild paresis. The balance-related gait
      parameters show a broad-based gait without inwardly rotated feet. No correlation
      was found between disease duration and the severity of the gait disorder and the
      central motor conduction time to the leg muscles and the abnormal gait
      parameters. The gait pattern did not differ between the 7 SSP cases and the 15
      HSP cases. CONCLUSIONS: We conclude that three-dimensional gait analysis can
      uncover specific features of such rare gait disorders, and may be used as an
      objective tool to quantify the impairment of gait parameters in patients with
      SSP/HSP and thus can be used to monitor disease progression and the effect of
      therapeutic interventions.

PMID- 15164191
TI  - Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic
      acid compared with slow-release levodopa/benserazid.
AB  - We aimed to compare the efficacy of valproic acid (VPA) on paresthesias and sleep
      in RLS to that of levodopa (LD). Twenty patients with idiopathic restless legs
      syndrome (RLS) were treated with 600 mg slow-release VPA and 200 mg slow-release
      LD+50mg benserazid in a randomized, placebo-controlled, cross-over, double-blind
      setting with polysomography (PSG) at the end of each 3-week treatment periods.
      There was no major difference between the efficacy of valproic acid or LD.
      Periodic leg movements in sleep (PLMS) and PLM arousal index (PLMAI)
      significantly decreased with LD (p < or= 0.005). However, LD, but not VPA,
      significantly increased arousals not associated with PLMS (p = 0.002). Decrease
      of intensity and duration of RLS symptoms were more pronounced with VPA (p < or=
      0.022) than with LD (NS). We conclude that slow-release VPA provides a treatment
      alternative for RLS.

PMID- 15164192
TI  - White matter hyperintensities and rating scales-observer reliability varies with
      lesion load.
AB  - BACKGROUND: Cerebral white matter hyperintensities (WMHs) are common in older
      people. Their presence correlates with cognitive decline and vascular risk
      factors. Various scales have been developed to quantify the amount and type of
      WMH, but with few observer reliability studies. We evaluated several scales in
      different cohorts to determine their observer reliability. METHODS: Two observers
      independently rated T2-weighted MR images from five groups (total n = 494: normal
      older subjects [97]; patients with minor stroke [221]; young insulin dependent
      diabetics [141]; maturity onset diabetics [10]; and hepatic encephalopathy [25]),
      using seven rating scales (Breteler, Fazekas, Longstreth, Mirsen, Shimada, Van
      Swieten and Wahlund). Inter-observer reliability was determined using Kappa
      statistics. RESULTS: Patients with maturity onset diabetes had the most WMHs and
      young insulin-dependent diabetics the least. Inter-observer reliability varied
      with the amount of WMH. In maturity onset diabetics (most WMHs) the weighted
      Kappas were: Breteler 0.74; Fazekas 0.89 and 0.72; Van Swieten 0.76 and 0.88; and
      in young insulin-dependent diabetics (least WMH): Breteler 0.3; Fazekas 0.2 and
      0.24; Van Swieten 0.39 and 0.30. These findings were consistent across the
      groups. CONCLUSION: WMH rating scale performance varied with WMH prevalence, and
      hence with subject cohort. In patients with most WMHs the apparent better kappas
      may reflect a "ceiling effect" rather than true better agreement. These factors
      should be considered in studies where risk factors for, or associations with, the
      early development of WMHs are being determined.

PMID- 15164193
TI  - Aprataxin mutations are a rare cause of early onset ataxia in Germany.
AB  - Aprataxin (APTX) mutations are the cause of ataxia with ocular motor apraxia type
      1(AOA1), an autosomal recessive disorder linked to chromosome 9p13.AOA1 seems to
      be one of the most frequent causes of recessive ataxia in Japan and Portugal. We
      screened a group of 165 early onset ataxia patients for APTX mutations and
      detected two non-related patients homozygous for the W293X nonsense mutation.
      Additionally, we describe several new transcript variants of the APTX gene and
      discuss their relevance for a sufficient mutation screening.

PMID- 15164195
TI  - Factors associated with pre-stroke dementia: the cracow stroke database.
AB  - BACKGROUND: Many stroke patients who fulfilled diagnostic criteria for dementia
      three months after stroke had a mental deterioration before stroke, implying an
      underlying neurodegenerative process. The goal of this study was to determine the
      factors associated with pre-stroke dementia in hospitalised-based population.
      SUBJECTS AND METHODS: Pre-stroke cognitive decline was evaluated in 250 stroke
      patients using the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE). Patients with IQCODE score > or=104 were classified as having pre
      stroke dementia. Clinical, radiological, and biochemical data of patients with
      and without pre-stroke dementia were compared. RESULTS: Pre-stroke dementia was
      found in 12% of 250 stroke patients. Patients with pre-stroke dementia were
      older, suffered more frequently from ischemic heart disease and diabetes, and had
      more frequently prior cerebrovascular disease. These patients had significantly
      more brain atrophy and number of old infarcts on CT than patients without pre
      stroke dementia. Serum gamma-globulins levels at admission were significantly
      higher in patients with pre-stroke dementia. In logistic regression analysis
      female gender (OR 3.47, CI 95% 1.25-9.64), history of previous stroke (OR 3.46,
      CI 95 % 1.26-9.51), the number of old infarcts on CT (OR 1.58, CI 95 % 1.08-2.33)
      and serum gamma-globulins level (OR 1.19, CI 95 % 1.02-1.40) were independently
      associated with pre-stroke dementia. CONCLUSIONS: Female gender and previous
      ischemic stroke are the most important determinants of pre-stroke cognitive
      decline.

PMID- 15164194
TI  - Physical therapy in Parkinson's disease: an open long-term rehabilitation trial.
AB  - The aim of this study was to evaluate the effects of prolonged physical therapy
      on disability in patients with Parkinson's disease. The study was designed as an
      open long-term trial over 20 weeks. Twenty slightly to moderately affected
      parkinsonian patients were included (Hoehn & Yahr stages: 1.5-3). A comprehensive
      rehabilitation program was applied three times a week in all patients.
      Pharmacological treatment was kept stable. Evaluations were performed at
      baseline, at the end of treatment and after 3 months. Following physical
      rehabilitation, there was a significant improvement in UPDRS (ADL and motor
      sections) scores, Self-assessment Parkinson's disease Disability Scale, Ten-Meter
      Walk test and Zung scale for depression. At 3-month follow-up clinical
      improvements were largely maintained. A sustained improvement of motor skills in
      PD patients can be achieved with a long-term comprehensive rehabilitation
      program.

PMID- 15164197
TI  - Many patients with dementia identified after stroke already had dementia present
      before.

PMID- 15164196
TI  - Frequency and determinants of prestroke dementia in a Chinese cohort.
AB  - Pre-existing dementia among patients with acute stroke is common, and adversely
      affects outcomes. Only a few studies have been published on prestroke dementia
      (PSD), none of which have investigated a consecutive stroke cohort in an Asian
      patient population. The objective of this study was to examine the prevalence and
      clinical correlates of PSD in Chinese stroke patients in Hong Kong. Close and
      reliable informants of 289 stroke patients who were consecutively admitted to the
      medical wards of a university-affiliated regional hospital completed the
      Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) within 1
      week after their relative's admission. The presence of PSD was defined as an
      average IQCODE score of >or= 4.00. In addition, a wide range of demographic and
      clinical variables were examined and recorded.Twenty-two participants (7.6%) had
      PSD. The frequency of PSD in the group of subjects (n = 73) who were assessed
      within 48 hours after their admission was 12.3%. Univariate analysis found that
      PSD was associated with age, marital status, atrial fibrillation (AF), previous
      transient ischaemic attack (TIA), leukoaraiosis, and cerebral atrophy index
      (CAI). Multivariate logistic regression suggested that CAI, age, AF, and past TIA
      were independent risk factors for PSD. The low prevalence of PSD in Chinese
      patients in comparison with their Caucasian counterparts may be due to the
      difference in the time frame of the assessment. Comparative studies involving
      both Caucasian and Chinese stroke patients are required to further explore the
      role of AF and TIA in the development of PSD in both Chinese and Caucasian
      patients.

PMID- 15164198
TI  - Granulomatous angiitis of the central nervous system revealing Hodgkin's disease.

PMID- 15164199
TI  - Clinical and radiological features of symptomatic cerebral perfusion failure due
      to carotid artery occlusion surgically corrected by extracranialintracranial
      bypass surgery.

PMID- 15164200
TI  - The diagnostic value of vestibular evoked myogenic potentials in multiple
      sclerosis.

PMID- 15164202
TI  - Persistent amnesia following right-sided vertebral artery dissection.

PMID- 15164201
TI  - Clinical evidence of fluconazole-induced carbamazepine toxicity.

PMID- 15164203
TI  - Acute disseminated encephalomyelitis associated with Borrelia burgdorferi.

PMID- 15164204
TI  - The future of headache.

PMID- 15164205
TI  - Giovanni Aldini (1762-1834).

PMID- 15164211
TI  - Entomotoxicology for the forensic toxicologist: much ado about nothing?
AB  - We present a series of 29 necropsies in which organic compounds (including
      benzodiazepines, barbiturates, antidepressants, phenothiazine, opiates,
      cannabinoids, meprobamate, digoxin and nefopam) were detected in arthropod larvae
      sampled on human corpses. No correlation was observed between drug concentrations
      in the larvae versus human samples. When tested, inter-larvae and inter-site
      variations of drug concentrations (i.e., within larvae when analyzed separately,
      and within anatomic sites when larvae were grouped according to their site of
      sampling) were enormous and not reproducible from one case to another, confirming
      that arthropod larvae are unreliable for quantitative toxicological analysis.
      Since drugs identified in maggots are always detectable in the cadaver too, we
      conclude that larvae analysis is of almost no interest for practical forensic
      casework.

PMID- 15164212
TI  - Determining time of death using blow fly eggs in the early postmortem interval.
AB  - A forensic entomology case is presented which is interesting for two reasons;
      firstly, it uses egg development, but secondly, it involves a case which is over
      20 years old, and was recently re-opened. The only entomological evidence was in
      the form of photographs. Usually, it is not possible to make any determinations
      from photographs alone, as species and age cannot be determined. However, this
      case was particularly unusual, as close up photographs taken by police at the
      crime scene showed the first egg eclosion. Weather records, developmental data
      and degree day accumulations, together with a knowledge of local species and
      their habitats, allowed determination of the time since death. Time of death was
      affirmed when the defendant was convicted of first degree murder more than 20
      years after the killing.

PMID- 15164215
TI  - Subileus caused by intestinal endometriosis: experience from three cases.

PMID- 15164213
TI  - Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis.
AB  - Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells
      are a good model system for studying the peripheral nervous system and the
      outgrowth of neurites. In addition to the dramatic changes observed in the
      cytoplasm, neuronal differentiation is also accompanied by striking changes in
      nuclear morphology. The large and sustained increase in nuclear transcription
      during neuronal differentiation requires synthesis of a large number of factors
      involved in pre-mRNA processing. We show that the number and composition of the
      nuclear subdomains called Cajal bodies and gems changes during the course of N
      ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies
      found in undifferentiated cells are largely devoid of the survival of motor
      neurons (SMN) protein product. As cells shift to a differentiated state, SMN is
      not only globally upregulated, but is progressively recruited to Cajal bodies.
      Additional SMN foci (also known as Gemini bodies, gems) can also be detected.
      Using dual-immunogold labeling electron microscopy and mouse embryonic
      fibroblasts lacking the coilin protein, we show that gems clearly represent a
      distinct category of nuclear body.

PMID- 15164214
TI  - Carcinoid tumours of the larynx.
AB  - The larynx is a rare site of origin of neuroendocrine carcinomas. They can be
      divided into typical, atypical and small cell tumours on the basis of their
      histopathological differentiation. The tumour histology and prognosis correlate
      closely. The typical carcinoid tumours are well differentiated with a benign
      course. Conservative surgery for local disease is the treatment and is associated
      with good survival. The atypical carcinoid tumours are poorly differentiated with
      an aggressive course. Response to radiotherapy and chemotherapy is poor. The
      treatment of choice is adequate total excision of the lesion with neck dissection
      if there is clinical evidence of cervical lymphadenopathy and a careful follow-up
      so as to recognise and treat any metastatic spread. We present two cases with
      similar history and clinical findings-one typical and the other atypical-and
      discuss the relevant literature.

PMID- 15164216
TI  - Clinical and pathologic considerations in a case of inflammatory myofibroblastic
      tumor of the spleen.
AB  - Inflammatory myofibroblastic tumors, also called inflammatory pseudotumors, are
      rare pseudosarcomatous proliferations. Their behavior is generally not
      aggressive, but in most instances they can simulate malignant neoplasms, from
      which they are impossible to distinguish before excision. One case of
      myofibroblastic tumor of the spleen in a 5-year-old boy is described: the patient
      was treated with a partial splenectomy, which was found to be the best approach
      for diagnosis and treatment. The purpose of this report is to call attention to
      this entity with peculiar histologic and immunohistochemical characteristics,
      which has to be included in the differential diagnosis of splenic lesions and may
      be excised by a nonaggressive procedure.

PMID- 15164217
TI  - True hermaphroditism in southern Africa: the clinical picture.
AB  - This is an 18-year (1985-2001) retrospective review of 85 patients with true
      hermaphroditism, with the aim of facilitating early recognition of this
      condition. Presentation of neonates and infants 6 months or younger, constituting
      54% of this cohort, were different from the older children. The presentation,
      clinical features and investigative results of all patients diagnosed with true
      hermaphroditism at a single South African paediatric surgical unit were reviewed.
      This paper highlights the previously reported high incidence (51%) of this
      condition, as well as some of the unusual features of true hermaphroditism in
      this region. Diagnosis of true hermaphroditism requires a high index of suspicion
      for subtle anomalies of the genitalia. Although there were no pathognomonic
      clinical features, the true hermaphrodite presents as a patient of either gender
      with a congenital anomaly of the genitalia. The child is likely to have a normal
      male phallus, bifid labio-scrotal folds, a perineal hypospadias and in 53% of
      patients there was a palpable gonad. The method of investigation, together with
      the results and some of the management dilemmas associated with true
      hermaphroditism in a Third World population are presented.

PMID- 15164219
TI  - Ultrasonic singing by the blue-throated hummingbird: a comparison between
      production and perception.
AB  - Blue-throated hummingbirds produce elaborate songs extending into the ultrasonic
      frequency range, up to 30 kHz. Ultrasonic song elements include harmonics and
      extensions of audible notes, non-harmonic components of audible syllables, and
      sounds produced at frequencies above 20 kHz without corresponding hearing range
      sound. To determine whether ultrasonic song elements function in intraspecific
      communication, we tested the hearing range of male and female blue-throated
      hummingbirds. We measured auditory thresholds for tone pips ranging from 1 kHz to
      50 kHz using auditory brainstem responses. Neither male nor female blue-throated
      hummingbirds appear to be able to hear above 7 kHz. No auditory brainstem
      responses could be detected between 8 and 50 kHz at 90 dB. This high-frequency
      cutoff is well within the range reported for other species of birds. These
      results suggest that high-frequency song elements are not used in intraspecific
      communication. We propose that the restricted hummingbird hearing range may
      exemplify a phylogenetic constraint.

PMID- 15164220
TI  - Length and angle measurements of the lower extremity in digital composite
      overview images.
AB  - We here introduce a digital scanning method for determining leg length and
      angles. The leg length and angle measurements, image quality and radiation dose
      were evaluated. A composite overview image was reconstructed from a series of
      individual images. In 45 overview images, the total leg length and the femoro
      tibial angle were determined by two radiologists, and the inter- and intra
      observer variability was examined in the light of the measured values as well as
      the subjective assessment of the image quality. A dose comparison was carried out
      with a series of conventional whole leg images. The mean standard deviation of
      the multiple measurements of leg length was 0.4 mm for researcher I and 0.5 mm
      for researcher II. The difference in the mean values of the measured leg lengths
      between the researchers was 0.3 mm. The mean standard deviation of the multiple
      measurements of the femoro-tibial angle was 0.1 degrees for both researchers. The
      difference in the mean values of the measured femoro-tibial angle between the
      researchers was 0.03 degrees. On average, the marks for the image quality awarded
      by researcher II with an average score of 2 were very significantly worse than
      those awarded by researcher I with an average score of 1.5. The mean entrance
      dose value determined was 0.16 mGy lower in the digital system (0.49 mGy) than
      that of the comparative conventional series (0.65 mGy). Where there is a large
      number of possible length and angle measurements, the proposed procedure offers
      the advantages of good image quality, digital image processing, measurements that
      are easy to perform, reproducible and accurate, and lower radiation dose, and it
      is superior to conventional whole leg images.

PMID- 15164221
TI  - [Recommendations for organ/tissue removal and use in research and teaching].

PMID- 15164223
TI  - [Collisiontumour composed of glioblastoma and meningioma-a case report].
AB  - A 51 year old caucasian male presented with headache, facial nerve paresis and
      continuing contraction of the visual field. CT scan revealed a singular
      intracerebral contrast enhancing lesion in the left frontal lobe.
      Intraoperatively the tumour was well demarcated. Frozen sections showed a high
      grade glioma. Paraffin sections revealed, in addition to the gliomatous
      component, some sharply demarcated nests of meningothelial cells.
      Immunohistochemistry with glial fibrillary acidic protein and epithelial membrane
      antigen confirmed a collision tumour consisting of a glioblastoma WHO-grade IV
      and a meningothelial meningioma WHO-grade I. The coincidence of these two
      different tumours at the same time and the same location leads us to the
      speculation, that the collision tumour might have been caused by malignant
      transformation of a reactive astrogliosis surrounding the meningioma.

PMID- 15164222
TI  - [Immunohistochemical identification of lymph vessels with D2-40 in diagnostic
      pathology].
AB  - D2-40 is an antibody that reliably detects human lymphatic endothelial cells.
      Because little is known about the extent to which other cells are stained, we
      have investigated this question in various tissues. Normal, reactive and
      neoplastic lymphatics (including lymphangiomas and Stewart-Treves syndrome) were
      stained by D2-40. Published findings indicate that some angiosarcomas and Kaposi
      are positive. Staining was also found in the following non-endothelial cells:
      mesothelial cells, follicular dendritic reticulum cells, Cajal cells, a few
      epithelial cells in the dermis, myoepithelial cells (e. g. breast), and basal
      cells (e. g. prostata), various mesenchymal cells. The following tumours were
      reactive: myofibroblastic tumours, gastrointestinal stromal tumour, mesothelioma,
      adenomatoid tumour, traumatic neuroma, seminoma, seminoma in situ and other
      testicular tumours, pleomorphic adenoma (one of two tumours positive), and
      follicular dendritic reticulum cell sarcoma. Despite this relatively broad
      spectrum of reactivity, we consider D2-40 to be the best commercially available
      antibody for the delineation of normal, reactive and neoplastic lymphatic
      endothelial cells.

PMID- 15164224
TI  - Grey-box pharmacokinetic/pharmacodynamic modelling of a euglycaemic clamp study.
AB  - Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a
      promising way of modelling the pharmacokinetics and pharmacodynamics of the in
      vivo system of insulin and glucose and to estimate model and derived PK/PD
      parameters. The concept behind grey-box modelling consists in using a priori
      physiological knowledge along with information from data in the estimation of
      model parameters. The PK/PD properties of two types of insulin are investigated
      in a euglycaemic clamp study where a single bolus of insulin is injected
      subcutaneously. The effect of insulin on the glucose disappearance is
      investigated by artificially maintaining a blood glucose concentration close to
      the normal fasting level. The infused glucose needed to maintain the clamped
      blood glucose concentration can therefore be used as a measure for the glucose
      utilization. The PK and PD parameters are successfully estimated simultaneously
      thereby describing the uptake, distribution, and effect of the two different
      types of insulin.

PMID- 15164225
TI  - Dynamic energy budget models with size-dependent hazard rates.
AB  - We formulate and analyze two dynamic energy budget models, a net assimilation
      model with constant allocation strategy and a net production model with a 2-stage
      allocation strategy, with the objective of determining strategies that maximize
      the expected lifetime reproductive energy. The per capita death rate depends on
      the organism's size, as for example when the main cause of death is predation. In
      the analysis of the net production model, the size at maturity is calculated
      along with the probability of reaching that size. We show that a small
      probability of survival to maturity is incompatible with the simple assumption of
      an exponential survival probability. We demonstrate that when the hazard rate is
      significantly greater for small individuals than large ones, it is possible for
      the optimum strategy to be for an individual to grow to a large size in spite of
      an arbitrarily small probability of survival to maturity. Numerical simulations
      indicate how the optimal allocation strategies depend on the parameter values.

PMID- 15164226
TI  - Human leg design: optimal axial alignment under constraints.
AB  - Alignment of joints with respect to the leg axis reduces the moment arm of
      external forces and therefore joint torques. Moreover, it affects the gearing of
      muscle forces and displacements. Thus, it influences tissue stress, cost of
      support and locomotion, and stability. Assuming that alignment is of general
      advantage we propose a mathematical criterion quantifying the axial alignment
      using the static torque equilibrium of a three-segment leg. Using this criterion
      derived from joint torque minimisation we asked for optimal leg designs (segment
      lengths and joint angles) at varied leg lengths. The trivial "straight is best"
      solution is excluded and the configuration space is restricted by geometrical
      constraints such as the ground contact. For different total leg lengths we could
      identify different optimal segment length combinations and appropriately adjusted
      joint angles. The extended human leg configuration characterised by a short foot
      and a combination of unequal ankle and knee angles emerges as a global optimum
      from our analysis. For crouched configurations allowing for larger leg extensions
      an angle symmetrical 1:1:1 segment length combination is best. The plantigrade
      optimum is enforced by the requirement of the distal segment (foot) being shorter
      than the opposite outer segment (thigh), as well as by the ground contact
      constraint. Different (e.g. digitigrade) geometries might be of advantage in
      different biological contexts with different constraints. The fact that small
      mammals use a crouched equal segment design implies that other locomotor
      requirements such as stability, strain rates, and acceleration distance per step
      might dominate.

PMID- 15164227
TI  - Large amplification in stage-structured models: Arnol'd tongues revisited.
AB  - The coexistence of periodic and point attractors has been confirmed for a range
      of stage-structured discrete time models. The periodic attractor cycles have
      large amplitude, with the populations cycling between extremely low and
      surprisingly high values when compared to the equilibrium level. In this
      situation a stable state can be shocked by noise of sufficient strength into a
      state of high volatility. We found that the source of these large amplitude
      cycles are Arnol'd tongues, special regions of parameter space where the system
      exhibits periodic behaviour. Most of these tongues lie entirely in that part of
      parameter space where the system is unstable, but there are exceptions and these
      exceptions are the tongues that lead to attractor coexistence. Similarity in the
      geometry of Arnol'd tongues over the range of models considered might suggest
      that this is a common feature of stage-structured models but in the absence of
      proof this can only be a useful working hypothesis. The analysis shows that
      although large amplitude cycles might exist mathematically they might not be
      accessible biologically if biological constraints, such as non-negativity of
      population densities and vital rates, are imposed. Accessibility is found to be
      highly sensitive to model structure even though the mathematical structure is
      not. This highlights the danger of drawing biological conclusions from particular
      models. Having a comprehensive view of the different mechanisms by which periodic
      states can arise in families of discrete time models is important in the debate
      on whether the causes of periodicity in particular ecological systems are
      intrinsic, environmental or trophic. This paper is a contribution to that
      continuing debate.

PMID- 15164228
TI  - Modelling the isotope enrichment of leaf water.
AB  - Farquhar and Gan have proposed a model for the spatial variation in the isotopic
      enrichment of H(2)(18)O across a leaf, which is specifically formulated for
      monocotyledoneous leaves. The model is based on the interaction between mass
      fluxes longitudinally within the xylem, and fluxes laterally through veinlets
      into the lamina mesophyll, where moisture leaves the leaf through transpiration.
      The lighter, more abundant, molecule H(2)(16)O escapes preferentially with the
      evaporating water, resulting in the enrichment of H(2)(18)O at these sites.
      Enriched water diffuses throughout the leaf, and it is this spatial distribution
      of enriched water which the model seeks to capture. In this paper we present a
      general formulation of the model in terms of mass flux, extending it to include
      variable transpiration rates across the leaf surface, as well as a tapering
      xylem. Solutions are developed for the general case and, since the solutions
      present in the form of Kummer functions, properties are established as well as
      methods for estimating the solutions under certain conditions relevant to the
      biology. The model output is compared with Gan's data collected from maize
      plants.

PMID- 15164229
TI  - Philadelphia (Ph) chromosome-positive thrombocythemia without features of chronic
      myeloid leukemia in peripheral blood: natural history and diagnostic
      differentiation from Ph-negative essential thrombocythemia.
AB  - We have evaluated the clinical symptoms, hematological features, and natural
      history of 3 cases and 20 reported cases described as Philadelphia chromosome
      positive (Ph+) essential thrombocythemia (ET). The presence of increased small
      mononuclear megakaryocytes in bone marrow smears and biopsy material in patients
      with pronounced thrombocytosis and no evidence of chronic myeloid leukemia (CML)
      in peripheral blood appeared to be a diagnostic clue to the diagnosis of Ph+
      (essential) thrombocythemia. As compared to cases of reactive thrombocytosis, the
      megakaryocytes in Ph+ thrombocythemia are smaller than normal ones and typically
      have hypolobulated round nuclei. This contrasts with the finding of clustered
      mature and enlarged megakaryocytes in Ph-negative true ET. Patients diagnosed as
      Ph+ ET may progress to CML and show a high tendency to myelofibrosis and blastic
      transformation. These observations indicate that both Ph+ ET and Ph+
      thrombocythemia associated with CML can be regarded as early manifestations of
      the chronic stable phase of CML.

PMID- 15164230
TI  - Vertical reduction mammaplasty.
AB  - The patients seeking our help for breast reduction are very often young and
      probably planning to have children later in their lives. Therefore it is most
      important to offer them a method of reduction mammaplasty that leaves as little
      scars and as much physiological function as possible. The vertical reduction
      mammaplasty as we perform it is a method that leaves normal sensibility in almost
      all cases, the possibility of lactation, little scarring and a pleasant form. The
      method can be used in all cases, ranging from mastopexy to reduction weights of
      over 2 kg of each breast. The vertical technique developed by Claude Lassus [1,2]
      and Madeleine Lejour [3,4,5,6] is a contemporary method of reduction that leaves
      few scars and conserves a maximum of physiological function. The method needs
      surgical skill and therefore it is not suitable for beginners in breast surgery.
      It is difficult to teach because it uses no patterns such as those of Strombeck
      [7] or McKissock [8] but it gives the breasts a new form based on the anatomical
      circumstances and wishes of the patients. Due to some unfavorable results in the
      early beginning often caused by too long a caudal part of the breast or a dog-ear
      at the end of the vertical scar, we have added some modifications to the method.
      We've heard of the same problems from several colleagues who no longer perform
      this method in major reduction plasties. We have been using this technique in all
      cases of breast reductions or mastopexies for the past 8 years.

PMID- 15164231
TI  - The transareolar incision for breast augmentation revisited.
AB  - Of the various possible incisions for breast augmentation, the transareolar
      access has gained only limited popularity. The potential side effects of this
      incision are said to be altered nipple sensation, impaired lactation, an
      increased rate of infections with capsular fibrosis, well visible scar formation
      with hypopigmentation, and the need for an additional access in case a breast
      ptosis correction should prove necessary at a later date. The purpose of this
      retrospective study was to judge advantages and limitations of transareolar
      breast augmentation, and to verify whether the reluctant attitude toward this
      surgical approach is justified. A sample of 18 patients with a transareolar,
      retropectoral breast augmentation was selected for a retrospective evaluation.
      The suitability of the technique in general was examined together with early
      postoperative complications, sensory changes, and late complications on the basis
      of an evaluation system for cosmetic surgical results. The study showed that only
      women with an areolar diameter of 3.5 cm or more without pronounced breast ptosis
      were suitable for the transareolar access. No early infections were noted. The
      rate of capsular fibrosis was 11%. Two years after breast augmentation, 16 women
      (89%) judged their breast sensation to be normal, but objective assessment showed
      that mean pressure and vibration sensation were moderately compromised in all
      parts of the breast. The scars were of good quality, with very little
      hypopigmentation. With appropriate patient selection, respecting the advantages
      and limitations, the transareolar incision has its definite place among the
      different incisions for breast augmentation.

PMID- 15164232
TI  - Benign symmetric lipomatosis (Madelung's disease): case reports and current
      management.
AB  - Benign symmetrical lipomatosis (BSL) is a rare disorder characterized by the
      presence of multiple, symmetric, nonencapsulated fat masses in the face, neck,
      and other areas. Typically, this entity has been related to the presence of three
      anterior bulges in the neck. The disorder was first described by Brodie in 1846.
      After that, Madelung in 1888 and Launois and Bensaude in 1898 characterized the
      disease. There are multiple synonyms for this disorder, such as Madelung's
      disease, Launois-Bensaude syndrome, and multiple symmetrical lipomatosis. Benign
      symmetric lipomatosis is usually described in adults from 30 to 60 years old,
      with an incidence of about 1 in 25,000 and a male-to-female ratio of 15:1 to
      30:1. Most cases have no hereditary pattern. More than 90% of the patients have
      associated alcoholism. The etiology of benign symmetric lipomatosis remains
      unknown, but an abnormal lipogenesis induced by catecholamines has been observed.
      The transformation of BSL to a malignant tumor is extremely rare. In the current
      report, the authors describe two cases of benign symmetric lipomatosis treated in
      their department and a review of the literature.

PMID- 15164233
TI  - Generation of human tumor-specific CTLs in HLA-A2.1-transgenic mice using
      unfractionated peptides from eluates of human primary breast and ovarian tumors.
AB  - HER-2/neu oncoprotein is overexpressed in a variety of human tumors and is
      associated with malignant transformation and aggressive disease. Due to its
      overexpression in tumor cells and because it has been shown to be immunogenic,
      this protein represents an excellent target for T-cell immunotherapy. Peptide
      extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by
      acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit
      in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+
      HER-2/neu+ tumor cells. Injections of ACE in transgenic mice induced CTLs capable
      of specifically lysing HER-2/neu+ tumor cell lines (also including the original
      HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201
      restricted fashion. Adoptive transfer of ACE-induced CTLs was sufficient to
      significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/
      neu+ human tumor cell lines. Cytotoxicity of such ACE-induced CTL lines was
      directed, at least as detected herein, also against the HER-2/ neu peptides HER-2
      (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes.
      HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon
      peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA
      A*0201-restricted manner and, when adoptively transferred, conferred sufficient
      protection in SCID mice inoculated with the same human tumor cell lines as above.
      However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of
      xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2
      [9(369)] or HER-2 [9(435)]). Even by administering mixtures of CTLs specific for
      each of these peptides, the prolongation of survival achieved was still inferior
      compared with that obtained with ACE-induced CTLs. This suggested that additional
      epitopes may contribute to the immunogenicity of such tumor-derived ACEs. Thus,
      immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an
      effective approach to generate multiple and potent CTL-mediated immune responses
      against HER-2/neu+ tumors expressing the appropriate HLA allele(s). By screening
      ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu
      sequence, it is feasible to identify immunodominant epitopes which may be used in
      mixtures as vaccines with enhanced efficacy in both the prevention and therapy of
      HER-2/neu+ malignancies.

PMID- 15164234
TI  - Detection of 14 alleles derived from the MHC class I A locus in cynomolgus
      monkeys.
AB  - A basic understanding of the major histocompatibility complex (MHC) class I,
      which, together with T-cell receptors, is a key player in antigen recognition by
      cytotoxic T lymphocytes, is necessary to study the cellular immune response to
      intracellular pathogens. The MHC has hardly been reported in cynomolgus monkeys (
      Macaca facicularis), although cynomolgus monkeys have been frequently used as the
      surrogate animal model. We attempted to determine the nucleotide sequences of the
      MHC class I A locus of cynomolgus monkeys ( Mafa-A) and eventually 34 independent
      sequences of Mafa-A were obtained from 29 cynomolgus monkeys. These 34 sequences
      were classified into 14 Mafa-A alleles according to the results of phylogenetic
      analyses using the neighbor-joining method. One to three Mafa-A alleles were
      obtained from a single animal. We also tried to establish a multiplex PCR-SSP
      method for convenient typing of Mafa-A alleles. cDNA from a family of cynomolgus
      monkeys, which is composed of four sirs and four dams, were examined by multiplex
      PCR-SSP. The result of multiplex PCR-SSP showed that an individual cynomolgus
      monkey had two or three Mafa-A alleles, suggesting that the A locus of cynomolgus
      monkeys might be duplicated.

PMID- 15164236
TI  - Permeability and the hidden area of lipid bilayers.
AB  - The passive water permeability of a lipid vesicle membrane was studied, related
      to the hydrostatic (not osmotic) pressure difference between the inner and the
      outer side of the vesicle in a water environment without additives. Each pressure
      difference was created by sucking a vesicle into a micropipette at a given
      sucking pressure. The part of the membrane sucked into the micropipette (the
      projection length) was measured as a function of time. The time dependence can be
      divided into two intervals. We put forward the idea that smoothing of membrane
      defects, accompanied by an increase of the membrane area, takes place during the
      initial time interval, which results in a faster increase of the projection
      length. In the second time interval the volume of the vesicle decreases due to
      the permeability of its membrane and the increase of the projection length is
      slower. The hidden area and the water permeability of a typical lipid bilayer
      were estimated. The measured permeability, conjugated to the hydrostatic pressure
      difference, is an order of magnitude higher than the known value of the
      permeability, conjugated to the osmotic pressure difference. A hypothesis, based
      on pore formation, is proposed as an explanation of this experimental result.

PMID- 15164237
TI  - Plankton diversity in the Bay of Fundy as measured by morphological and molecular
      methods.
AB  - Phytoplankton have traditionally been identified based on morphological
      characteristics. However, identifications based on morphology are time-consuming,
      require expertise in taxonomy, and often fail to distinguish differences among
      the multitudes of minute, nondescript planktonic organisms. Molecular techniques,
      which have revealed new insights into bacterial and picoplankton communities, may
      also enhance our knowledge of the diversity among communities of larger plankton.
      We compared plankton identifications and community assessments based on the two
      types of techniques (morphological vs molecular) for surface seawater samples
      collected on 2 May, 31 July and 25 September 2000 from several sampling stations
      in the Bay of Fundy. Phytoplankton captured in surface bucket samples were
      quantified and identified based on morphology. DNA was extracted from plankton
      communities (5-100 microm in diameter) collected by filtration, and 18S rRNA gene
      fragments were amplified with primers specific for eukaryotes. Denaturing
      gradient gel electrophoresis (DGGE) was used to develop DNA profiles of
      eukaryotic phylogenetic diversity and to select cloned 18S rDNA fragments for
      sequencing. Both morphological and molecular methods showed great community
      diversity. However, the communities identified with the two different types of
      techniques were starkly different. Morphological abundances and taxon richness
      were lowest in the May samples, whereas the number of DGGE bands was highest in
      May and July. Morphological identifications showed a succession of dominant
      organisms through time. Whereas neither diatoms nor dinoflagellates were dominant
      in May, diatoms and a few dinoflagellates were dominant in July and September. In
      contrast, few 18S rDNA sequences were related to rDNA sequences of known
      identity, and furthermore, few diatoms were identified in the molecular analyses.
      Molecular phylogenetic analysis indicated the presence of many novel organisms,
      several of which were most closely related to other unidentified sequences from
      diverse marine environments representing new lineages. Our results support the
      ideas that we are just beginning to uncover the diversity of eukaryotic marine
      organisms and that there may be many more ubiquitous, microeukaryotic plankton
      than previously realized. Our results suggest that both types of methods capture
      only a portion of the community. Morphological methods may be more adept at
      capturing the phototrophic organisms within the community. However, just as for
      bacteria and picoplankton, molecular techniques can enhance our understanding of
      plankton diversity, particularly by detecting previously unidentified organisms.

PMID- 15164238
TI  - Changes in Synechococcus population size and cellular ribosomal RNA content in
      response to predation and nutrient limitation.
AB  - A mathematical model of predator-prey interactions was used to predict the
      relationship between population size and cellular growth rate in a two-tiered
      trophic system consisting of Synechococcus PCC 6301 and Tetrahymena pyriformis.
      As predicted, axenic chemostat cultures of Synechococcus responded to increased
      nutrient availability by expanding the equilibrium population size without a
      concurrent change in growth rate. Likewise, the addition of the predator
      Tetrahymena pyriformis decreased the Synechococcus population size by 85% and
      increased the Synechococcus growth rate. Synechococcus populations in the surface
      waters of the Gulf of Mexico were sampled to ascertain whether the relationship
      between population size and cellular 16S rRNA concentration conformed to that
      predicted by the model. Direct counts of autofluorescent cells in size
      fractionated seawater samples provided an estimate of Synechococcus population
      size. The growth rate of in situ populations was estimated by measuring the
      extent of hybridization of an oligonucleotide probes complementary to
      Synechococcus 16S rRNA, based on evidence that ribosomal RNA content increases
      concurrently with growth rate. The comparison of in situ population sizes and
      specific growth rates revealed that relatively large Synechococcus populations
      were growing slowly, indicative of nutrient limitation, and that quickly growing
      populations were relatively small, as predicted for predator-limited populations.

PMID- 15164239
TI  - Recovery of GFP-labeled bacteria for culturing and molecular analysis after cell
      sorting using a benchtop flow cytometer.
AB  - Exciting opportunities exist for the application of simple fluorescence-activated
      cell sorting (FACS) to microbiology. The technology is widely available, but
      critical reports on the efficiency of cell sorting using benchtop instruments are
      lacking. It is vital that single cell sorting be of the highest purity possible.
      If purity is compromised detrital material or unwanted cells will be captured
      along with target cells of interest. Here, the isolation of fluorescent bacteria
      using a benchtop FACSCalibur-sort flow cytometer is described. The efficiency and
      purity of isolated cells was determined using fluorescence microscopy, culturing,
      and molecular analysis. To achieve high purity it was essential that the total
      event rate did not exceed 300 cells per second. This instrument was capable of
      recovering >55% sorted Escherichia coli cells, coupled with a purity exceeding
      99%. However, the purity of recovered cells was substantially reduced (<25%) when
      the event rate increased. Cell sorting onto polycarbonate membranes did not
      reduce the ability of E. coli to form colonies, and sorting of ~1000 E. coli
      cells was sufficient for 16S rDNA amplification. Additionally, as few as 100
      isolated Erwinia sp. carrying the gfp gene were amplified using seminested PCR
      targeting the single copy gfp gene. With such low numbers of bacteria being
      required for molecular identification, FACS can be achieved without the
      requirement for high-speed droplet cell sorters.

PMID- 15164240
TI  - Micrococcus luteus -- survival in amber.
AB  - A growing body of evidence now supports the isolation of microorganisms from
      ancient materials. However, questions about the stringency of extraction methods
      and the genetic relatedness of isolated organisms to their closest living
      relatives continue to challenge the authenticity of these ancient life forms.
      Previous studies have successfully isolated a number of spore-forming bacteria
      from organic and inorganic deposits of considerable age whose survival is
      explained by their ability to enter suspended animation for extended periods of
      time. However, despite a number of putative reports, the isolation of non-spore
      forming bacteria and an explanation for their survival have remained enigmatic.
      Here we describe the isolation of non-spore-forming cocci from a 120-million-year
      old block of amber, which by genetic, morphological, and biochemical analyses are
      identified as belonging to the bacterial species Micrococcus luteus. Although
      comparison of 16S rRNA sequences from the ancient isolates with their modern
      counterparts is unable to confirm the precise age of these bacteria, we
      demonstrate, using complementary molecular and cell biological techniques,
      evidence supporting the view that these (and related modern members of the genus)
      have numerous adaptations for survival in extreme, nutrient-poor environments,
      traits that will assist in this bacteria's persistence and dispersal in the
      environment. The bacteria's ability to utilize succinic acid and process terpine
      related compounds, both major components of natural amber, support its survival
      in this oligotrophic environment.

PMID- 15164241
TI  - A highly selectable and highly transferable Ti plasmid to study conjugal host
      range and Ti plasmid dissemination in complex ecosystems.
AB  - A conjugal donor system, ST2, was constructed to study the conjugal dissemination
      of a Ti plasmid to wild-type recipient bacteria in vitro and in situ. The system
      consisted of a polyauxotrophic derivative of C58 harboring a hyperconjugative and
      highly selectable Ti plasmid, pSTiEGK, which was constructed by inserting a
      multiple antibiotic resistance cassette in the traM- mcpA region of pTiC58Delta
      accR. ST2 transfers pSTiEGK constitutively at frequencies up to 10(-1) to
      plasmidless Agrobacterium recipients. The host range of pSTiEGK includes all the
      known genomic species of Agrobacterium, indigenous soil agrobacteria and some
      Rhizobium and Phyllobacterium spp. All transconjugants became pathogenic upon
      acquisition of the Ti plasmid and were also able to transfer pSTiEGK by
      conjugation. This host range was indistinguishable from that of its wild-type
      parent pTiC58, and therefore pSTiEGK constitute a valid proxy to study the
      dissemination of Ti plasmids directly in the environment. Transconjugants can be
      selected on a combination of four antibiotics, which efficiently prevents the
      growth of the indigenous microbiota present in complex environments. The transfer
      of pSTiEGK to members of the genus Agrobacterium was affected primarily by the
      plasmid content of the recipient strain (10(3)- to 10(5)-fold reduction), e.g.,
      the presence of incompatible plasmids. As a consequence, a species should be
      considered permissive to Ti transfer whenever one permissive isolate is found.

PMID- 15164242
TI  - Determining parameters of the numerical response.
AB  - The numerical response, the change in specific growth rate with food
      concentration, is a fundamental component of many aquatic microbial studies.
      Accurately and precisely determining the parameters of this response is essential
      to obtain useful data for both aut- and synec-ological studies. In this work we
      emphasize four points that are often ignored in designing numerical response
      experiments: (1) the inclusion of subthreshold concentrations (i.e., where growth
      rate is negative) in the experimental design; (2) an appropriate allocation of
      effort, i.e., the superiority of choosing more individual prey concentrations
      rather than replicating fewer; (3) the potential superiority of replicating
      experiments rather than simply replicating treatment in a single experiment; and
      (4) the placement of most measurements near the lower end of the concentration
      gradient, well below the asymptote, possibly following a geometric progression.
      We illustrate the first point by examining a small subset of published data on
      planktonic oligotrich ciliates and then, using a Monte Carlo simulation,
      rigorously evaluate the experimental design, supporting the remaining points.

PMID- 15164243
TI  - Total mesorectal excision results in low local recurrence rates in lymph node
      positive rectal cancer.
AB  - PURPOSE: Most series report lymph node involvement as the main predictor for
      local recurrence. The principal lymphatic drainage of the rectum is to nodes in
      the mesorectum and then nodes along the superior rectal and inferior mesenteric
      arteries. If total mesorectal excision provides adequate block dissection of the
      lymphatics of the rectum, good local control with low rates of local recurrence
      should be achieved even in node-positive disease. METHODS: Prospective data on
      all rectal cancers have been collected since 1978; 170 patients with Dukes C
      rectal cancer have undergone anterior resection and total mesorectal excision. We
      did not perform any internal iliac node dissections. Follow-up data were analyzed
      for local recurrence and distant recurrence. RESULTS: The local recurrence rate
      was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes
      C ( P = 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18
      percent for Dukes B, and 37 percent for Dukes C ( P = 0.0001). CONCLUSIONS: If
      surgical priority is given to the difficult task of excision of the whole
      mesorectum, anterior resection with total mesorectal excision in node-positive
      rectal cancer, local recurrence rates of < 10 percent can be achieved.

PMID- 15164245
TI  - Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus
      initially managed with combined modality therapy.
AB  - PURPOSE: Primary chemoradiation failure for epidermoid carcinoma of the anus is
      treated by surgical resection. This study evaluates the outcome of salvage
      surgery at one institution. METHODS: All patients (n = 177) with a diagnosis of
      epidermoid carcinoma of the anus undergoing surgery since 1980 were reviewed.
      After criteria-based exclusion (n = 115), the remaining patients (n = 62) were
      analyzed. Kaplan-Meier survival analysis was performed on abdominoperineal
      resection/low anterior resection patients. Variable comparisons were made using
      log-rank and Cox regression analyses. Inguinal lymph node dissection patients (n
      = 5) were analyzed separately. RESULTS: Median follow-up was 24.2 months.
      Actuarial five-year survival in all abdominoperineal resection/low anterior
      resection patients (n = 57) was 33 percent (median, 34.1 months). Univariate
      predictors of decreased survival were tumor size > 5 cm or adjacent organ
      involvement at salvage, positive nodal disease at salvage, and positive margins.
      Independent predictors of decreased survival were the same except for tumor size
      or adjacent organ involvement at salvage (not significant). Patients undergoing
      potentially curative resections (n = 47) had an actuarial five-year survival of
      40 percent (median, 49 months). The univariate and multivariate predictors of
      both decreased survival and recurrence in this subgroup included: disease
      persistence after chemoradiation and nodal disease at salvage. Tumor size > 5 cm
      or adjacent organ involvement at salvage predicted recurrence with only
      univariate analysis. Interestingly, actuarial five-year survival after
      potentially curative resection for recurrence after chemoradiation was 51 percent
      (as opposed to 31 percent for persistence). After potentially curative
      resections, most documented recurrences (79 percent) occurred within two years
      and were locoregional (74 percent). Actuarial five-year recurrence-free survival
      was 46 percent. Three of five inguinal lymph node dissection patients were alive
      without disease at 21.2, 81.7, and 84.3 months. CONCLUSIONS: Salvage surgery
      after failed chemoradiation therapy has a reasonable chance of cure. Favorable
      independent prognostic factors include recurrence ( vs. persistence) after
      chemoradiation (when salvage is potentially curative), absence of nodal disease
      at salvage, and negative margins. Salvage inguinal lymph node dissection after
      failed chemoradiation therapy also is potentially curative.

PMID- 15164246
TI  - Colorectal stenting for malignant and benign disease: outcomes in colorectal
      stenting.
AB  - INTRODUCTION: Self-expanding metal stents are now an established treatment for
      malignant colonic obstruction. Favorable outcomes have been reported both for
      cancer palliation and treatment of acute obstruction as a "bridge" to surgery.
      However, little data exists regarding the use of stents for benign colonic
      obstruction. METHODS: All cases of colonic stent insertion occurring between
      December 1996 to October 2002 were reviewed. During the study period, 36 patients
      with malignant obstruction and 6 patients with benign obstructive disease
      underwent placement of self-expandable stents using a combined endoscopic and
      fluoroscopic technique. RESULTS: Stent placement was successful in 36 of 42
      patients (86 percent). Complications occurred in 16 of 36 patients (44 percent):
      migration (n = 7), reobstruction (n = 5), perforation (n = 2), fistula formation
      (n = 1), and stent fracture (n = 1). Stent placement was successful in 100
      percent of patients with benign strictures but poststent migration was frequent
      (2/6). CONCLUSIONS: Stent insertion provided an effective outcome in patients
      with malignant colonic obstruction as a palliative and preoperative therapy.
      Although a relatively high migration rate was observed in patients with benign
      strictures, stenting was still effective in providing luminal patency (median
      follow-up, 7.5 months). Stenting should be considered as a first-line treatment
      for malignant strictures and as a potential therapy for selected benign
      strictures.

PMID- 15164247
TI  - Complications and survival after surgery for rectal cancer in patients younger
      than and aged 75 years or older.
AB  - PURPOSE: An increasing number of rectal cancer patients are elderly and have
      comorbid medical diseases. This study was designed to compare perioperative
      morbidity, mortality, and survival after surgery for rectal cancer in patients
      younger than and aged 75 years or older. METHODS: Between 1980 and 1997, 294
      patients with rectal cancer were admitted to the Fourth Department of Surgery,
      Helsinki University Central Hospital. Of these, 95 (32 percent) were aged 75 or
      older and comprise the elderly group. RESULTS: Major curative operation was
      possible in 59 of 95 patients in the elderly group and in 147 of 199 patients in
      the younger age group. Among those operated on with curative intent, 20 of 59
      patients (34 percent) in the older age group and 39 of 147 patients (27 percent)
      in the younger age group had complications ( P = 0.31). Thirty-day mortality was
      2 percent (n = 1) and 0, respectively. Although five-year crude survival was
      significantly lower in the older age group (43 vs. 65 percent, P = 0.01), five
      year cancer-specific survival (60 vs.70 percent, P = 0.6) and disease-free, five
      year survival (60 vs. 69 percent, P = 0.4) were similar in both groups. Patients
      (n = 17) treated with local excision had a cancer-specific survival of 81 and 83
      percent in younger and older age groups, respectively. After palliative
      resection, the two-year survival was similar (20 vs. 24 percent) in both age
      groups. Ten elderly patients (11 percent) were not operated on at all in contrast
      to two patients (1 percent) younger than aged 75 years ( P = 0.003). CONCLUSIONS:
      Major, curative, rectal cancer surgery in selected elderly patients can be
      performed with similar indications, perioperative morbidity, and mortality, as
      well as five-year, cancer-specific and disease-free survival as in younger
      patients.

PMID- 15164248
TI  - Colorectal cancer in Denmark 1943-1997.
AB  - PURPOSE: This article reports the incidence rates of colon and rectal cancer in
      Denmark during 55 years of data registration and estimates the number of cases
      identified attributable to four modifiable risk factors and potentially
      preventable. METHODS: On the basis of reports in the nationwide, population
      based, Danish Cancer Registry, we calculated age-standardized, period-specific,
      incidence rates and age and birth cohort-specific incidence rates. To calculate
      the population attributable risk, relative risk estimates were obtained from meta
      analyses, case-control, and prospective cohort studies, combined with data from
      surveys of the consumption of alcohol, red meat, vegetables, and level of
      physical activity. RESULTS: For both genders, the incidence rate of colon cancer
      increased, whereas the incidence rate for rectal cancer decreased during the
      period 1943 to 1997. The decrease in the incidence rate of rectal cancer was
      observed for both genders, but the incidence rate among males was higher than
      that among females. The proportion of cases that could have been prevented if the
      Danish population had not been exposed to the four known risk factors varied from
      0 to 15 percent for each of the four risk factors. CONCLUSIONS: This study shows
      that the incidence rate of colon cancer has increased, whereas that of rectal
      cancer has decreased in Denmark during 55 years of observation. The potentially
      preventable proportions of incident cases are substantial but not as high as
      might have been expected.

PMID- 15164249
TI  - Carbohydrate-electrolyte (E-Lyte) solution enhances bowel preparation with oral
      fleet phospho-soda.
AB  - PURPOSE: Bowel preparation with oral sodium phosphate can cause symptomatic
      dehydration and electrolyte disturbances. This randomized, controlled trial was
      designed to evaluate whether carbohydrate-electrolyte (E-Lyte) solution enhanced
      bowel preparation and improved patient acceptance with oral sodium phosphate.
      METHODS: A total of 187 consecutive adults undergoing colonoscopy by two
      endoscopists were randomized to receive two packets of oral sodium phosphate
      (Fleet Phospho-soda) with or without additional supplement of a carbohydrate
      electrolyte (E-Lyte) solution. All patients and endoscopists completed a
      standardized questionnaire. Urine-specific gravity and serum biochemistry were
      randomly performed in 150 and 50 patients, respectively. RESULTS: Ninety patients
      were randomized to have oral sodium phosphate with E-Lyte supplements (Group 1)
      and 94 patients to sodium phosphate without E-Lyte supplements (Group 2). The
      groups were similar in age and gender, indication for colonoscopy, and previous
      colonic surgery. Patients taking E-Lyte supplement had significantly less
      dizziness (none, 80 vs. 56 percent; P < 0.001) and a trend toward less nausea
      (none, 70 vs. 56 percent; P = 0.05). All patients in Group 1 completed the bowel
      preparation as opposed to 3 percent of Group 2 being unable to complete the
      preparation. Hypokalemia was significantly more frequent ( P = 0.008) in Group 2
      patients without E-Lyte supplements. More patients in Group 2 needed intravenous
      rehydration (11 vs. 4 percent). Differences in serum creatinine and urine
      specific gravity suggested possibly a lesser degree of hypovolemia in patients
      taking E-Lyte supplements. The quality of bowel cleansing in patients taking E
      Lyte supplements was considered better by both the endoscopists and patients.
      CONCLUSIONS: Carbohydrate-electrolyte (E-Lyte) solution protects against
      hypokalemia, improves patient tolerability, and may enhance use of oral sodium
      phosphate as a bowel-preparation agent.

PMID- 15164250
TI  - Detection of lymphatic micrometastases in patients with stages I and II
      colorectal cancer: impact on five-year survival.
AB  - PURPOSE: Despite having removed the whole macroscopic disease (curative intent
      surgery), one of five patients with Stages I and II colorectal cancer will
      develop recurrence. Lymphatic micrometastases detected by immunohistochemistry
      could be one of explanation for recurrence and cancer-related death in patients
      without lymph node involvement at light microscopy. However, the biologic
      importance of micrometastases remains unclear. This study was designed to
      determine the impact of micrometastases in five-year survival in patients with
      Stages I and II colorectal cancer. METHODS: This retrospective study included
      patients operated on between May 1989 and January 1999 for colorectal cancer
      without histopathologic lymph node involvement. Patients who received any
      adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes
      was performed with antipancytokeratin antibodies. Follow-up data were obtained
      from the clinical database and death certificates. Survival was estimated by the
      Kaplan-Meier method and compared by the log-rank test. RESULTS: Micrometastases
      were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was
      90.7 (range, 11-160) months. Seventeen cancer-related deaths occurred during
      follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1
      percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559).
      Cancer-specific five-year survival was 87 percent in the whole group and 81
      percent in patients positive for micrometastases vs. 90 percent in negative
      patients ( P = 0.489). CONCLUSIONS: The presence of micrometastases in patients
      with Stages I and II colorectal cancer seems not to have any impact on cancer
      specific survival.

PMID- 15164251
TI  - Cap polyposis: further experience and review.
AB  - PURPOSE: Cap polyposis is characterized by the presence of inflammatory polyps
      with a "cap" of granulation tissue. It may represent one end of a spectrum of
      conditions caused by chronic straining. This experience represents the second
      largest reported series of cap polyposis. METHODS: The case notes of all patients
      with histologically proven cap polyposis were reviewed retrospectively and
      clinicopathologic features identified. A MEDLINE search was performed from 1985
      to 2002 using cap polyps, polyposis, and inflammatory polyp as key words and
      further hand search was undertaken of key references. RESULTS: Eleven cases (9
      males; median age, 20 (range, 15-54 years) of cap polyposis were diagnosed
      between 1993 and 2002. The commonest presenting symptoms were rectal bleeding (82
      percent) and mucous diarrhea (46 percent). Chronic straining at stool and
      constipation were noted in seven of these patients (64 percent). Digital rectal
      examinations revealed polypoidal masses in the rectum in four patients (36
      percent). All patients underwent colonoscopy. The commonest site of involvement
      was in the lower rectum (82 percent). One patient had polyps in the sigmoid colon
      and one patient in the transverse colon. Of 11 patients, 2 defaulted follow-up
      after colonoscopy. Three patients with solitary polyps had complete resolution of
      symptoms after polypectomy and remained symptom-free at three-month follow-up.
      The remaining six patients had persistent symptoms and required surgical
      intervention. Four underwent anterior resection and were all symptom-free at
      median of 48 (range, 18-72) months after surgery. One patient had transanal
      excision of rectal polyps and had recurrence at three months after surgery. This
      patient refused further treatment and remains symptomatic to date. One patient
      presented with recurrence of polyps at the coloanal anastomosis soon after a pull
      through procedure. Total colectomy and ileal pouch-anal anastomosis was performed
      and the patient was free of symptoms at four months after surgery. CONCLUSIONS:
      Cap polyposis is eminently treatable with good long-term prognosis and function.
      Patients with solitary cap polyp respond well to endoscopic polypectomy. However,
      patients with multiple polyps and concurrent anorectal pathology require surgical
      resection.

PMID- 15164252
TI  - Synchronous colorectal neoplasms in patients with colorectal cancer: predisposing
      individual and familial factors.
AB  - PURPOSE: Patients with colorectal cancer have an increased risk for developing
      synchronous and metachronous neoplasms. However, besides those cases with
      inherited disorders predisposing to tumor multicentricity, it is unknown which
      patients are prone to this condition. This study was designed to identify
      individual and familial characteristics associated with the development of
      synchronous colorectal neoplasms in patients with colorectal cancer. METHODS:
      During a one-year period, all patients with colorectal cancer attended in 25
      Spanish hospitals were included. Exclusion criteria were colorectal cancer
      developed in the context of familial adenomatous polyposis or inflammatory bowel
      disease, refusal to participate in the study, incomplete family history, and
      inadequate examination of the colon and rectum. In addition to demographic,
      clinical, pathology, molecular (microsatellite instability status), and familial
      characteristics, presence of synchronous colorectal neoplasms (adenoma or
      carcinoma) were analyzed. RESULTS: A total of 1,522 patients were included in the
      study. Synchronous colorectal neoplasms were documented in 505 patients (33.2
      percent): adenoma (n = 411), carcinoma (n = 27), or both (n = 67). Development of
      these lesions was associated with male gender (odds ratio, 1.94; 95 percent
      confidence interval, 1.43-2.65), personal history of colorectal adenoma (odds
      ratio, 3.39; 95 percent confidence interval, 1.58-7.31), proximal location of
      primary tumor (odds ratio, 1.40; 95 percent confidence interval, 1.02-1.94),
      tumor TNM Stage II (odds ratio, 1.31; 95 percent confidence interval, 1.15-4.66),
      mucinous carcinoma (odds ratio, 1.89; 95 percent confidence interval, 1.19-2.99),
      and family history of gastric cancer (odds ratio, 2.03; 95 percent confidence
      interval, 1.17-3.52). CONCLUSIONS: Based on individual and familial
      characteristics associated with synchronous colorectal neoplasms, it has been
      possible to identify a subgroup of patients with colorectal cancer prone to tumor
      multicentricity with potential implications on the delineation of preventive
      strategies.

PMID- 15164253
TI  - Pregnancy and delivery before and after ileal pouch-anal anastomosis for
      inflammatory bowel disease: immediate and long-term consequences and outcomes.
AB  - PURPOSE: This study was designed to evaluate pregnancy, delivery, and functional
      outcome in females before and after ileal pouch-anal anastomosis for chronic
      ulcerative colitis. METHODS: From a prospective database of 1,454 patients who
      underwent ileal pouch-anal anastomosis for chronic ulcerative colitis between
      1981 and 1995, a standardized questionnaire was sent to all female patients aged
      40 years or younger at the time of ileal pouch-anal anastomosis (n = 544).
      RESULTS: The response rate was 83 percent (450/544) with a mean follow-up after
      ileal pouch-anal anastomosis of 13 years. A total of 141 females were pregnant
      after the chronic ulcerative colitis diagnosis, but before ileal pouch-anal
      anastomosis (236 pregnancies; mean, 1.7) and 87 percent delivered vaginally. A
      mean of five (range, 1-16) years after ileal pouch-anal anastomosis, 135 females
      were pregnant (232 pregnancies; mean, 1.7). Comparison of pregnancy and delivery
      before and after ileal pouch-anal anastomosis in the same females (n = 37) showed
      no difference in birth weight, duration of labor, pregnancy/delivery
      complications, vaginal delivery rates (59 percent before vs. 54 percent after
      ileal pouch-anal anastomosis), and unplanned cesarean section (19 vs.14 percent).
      Planned cesareans occurred only after ileal pouch-anal anastomosis and were
      prompted by obstetrical concerns in only one of eight. Pouch function at first
      follow-up after delivery (mean, 7 months) was similar to pregravida function.
      After ileal pouch-anal anastomosis, daytime stool frequency was the same after
      delivery as pregravida (5.4 vs. 5.4, not significant) but was increased at the
      time of last follow-up (68 months after delivery; 5.4 vs. 6.4; P < 0.001). The
      rate of occasional fecal incontinence also was higher (20 percent after ileal
      pouch-anal anastomosis and 21 percent pregravida vs. 36 percent at last follow
      up; P = 0.01). No difference in functional outcome was noted compared with
      females who were never pregnant after ileal pouch-anal anastomosis (n = 307). Age
      and becoming pregnant did not affect the probability of pouch-related
      complications, such as stricture, pouchitis, and obstruction. CONCLUSIONS:
      Successful pregnancy and vaginal delivery occur routinely in females with chronic
      ulcerative colitis before and after ileal pouch-anal anastomosis. The method of
      delivery should be dictated by obstetrical considerations. Pouch function and the
      incidence of complications in females with pregnancies seem largely unaffected
      long-term.

PMID- 15164254
TI  - Female infertility after ileal pouch-anal anastomosis for ulcerative colitis.
AB  - PURPOSE: Although ulcerative colitis commonly affects young females, the impact
      of ulcerative colitis and its treatment on female fertility have not been well
      studied. The purpose of this survey was to examine the impact of ulcerative
      colitis and ileal pouch-anal anastomosis on female reproductive ability. METHODS:
      Demographic, reproductive history, and disease history information were obtained
      via a questionnaire mailed to females who had pelvic pouch surgery or
      nonoperative management for ulcerative colitis. Based on age at diagnosis, age at
      surgery, and marital status, 153 females who had pelvic pouch surgery and 60
      females who had nonoperative management for ulcerative colitis were identified
      for inclusion. Patients were asked if they attempted to become pregnant, when
      relative to their diagnosis or surgery, and if they were successful. Married or
      cohabiting females aged 18 to 44 years who failed to become pregnant during 12
      months of unprotected intercourse were defined as infertile. RESULTS: The
      infertility rate was significantly higher in females who had pelvic pouch surgery
      compared with females managed nonoperatively (59/153 (38.1 percent) vs. 8/60
      (13.3 percent), respectively; P < 0.001). There was no difference in female
      fertility after diagnosis with ulcerative colitis compared with before diagnosis
      (odds ratio, 0.68; P = 0.23). In contrast, there was a 98 percent reduction in
      fertility after pelvic pouch surgery compared with before surgery (odds ratio,
      0.021; P < 0.0001). By logistic regression, increasing age was the only factor
      associated with failure to become pregnant after surgery (odds ratio, 1.136 per
      additional year of age; P = 0.027). CONCLUSIONS: Females with ulcerative colitis
      who are managed nonoperatively have normal fertility, which suggests that
      ulcerative colitis and medical therapy do not decrease female reproductive
      ability. After pelvic pouch surgery for ulcerative colitis, female fertility is
      significantly decreased and this problem should be discussed routinely with
      patients considering this procedure.

PMID- 15164255
TI  - Radiological assessment of hydrocephalus: new theories and implications for
      therapy.
AB  - It is almost a century since Dandy made the first experimental studies on
      hydrocephalus, but its underlying mechanism has been unknown up to now. The
      conventional view is that cerebrospinal fluid (CSF) malabsorption due to
      hindrance of the CSF circulation causes either obstructive or communicating
      hydrocephalus. Analyses of the intracranial hydrodynamics related to the pulse
      pressure show that this is an over-simplification. The new hydrodynamic concept
      presented here divides hydrocephalus into two main groups, acute hydrocephalus
      and chronic hydrocephalus. It is still accepted that acute hydrocephalus is
      caused by an intraventricular CSF obstruction, in accordance with the
      conventional view. Chronic hydrocephalus consists of two subtypes, communicating
      hydrocephalus and chronic obstructive hydrocephalus. The associated malabsorption
      of CSF is not involved as a causative factor in chronic hydrocephalus. Instead,
      it is suggested that increased pulse pressure in the brain capillaries maintains
      the ventricular enlargement in chronic hydrocephalus. Chronic hydrocephalus is
      due to decreased intracranial compliance, causing restricted arterial pulsations
      and increased capillary pulsations. The terms "restricted arterial pulsation
      hydrocephalus" or "increased capillary pulsation hydrocephalus" can be used to
      stress the hydrodynamic origin of both types of chronic hydrocephalus. The new
      hydrodynamic theories explain why third ventriculostomy may cure patients with
      communicating hydrocephalus, a treatment incompatible with the conventional view.

PMID- 15164257
TI  - Epidemiological features of invasive and noninvasive group A streptococcal
      disease in the Netherlands, 1992-1996.
AB  - A prospective, nationwide, laboratory-based surveillance of invasive group A
      streptococcal infections was conducted in the Netherlands from 1992 through 1996.
      Clinical and demographic data were obtained and all isolates were T/M typed. All
      noninvasive group A streptococcal isolates were registered from 1994 through
      1996. A total of 880 patients with invasive streptococcal disease were
      identified. The annual incidence was found to be 2.2 per 100,000. Predominant M
      types were M1 (21%), M3 (11%), M6 (5%), M12 (5%), and M28 (8%). Particular age
      and M-type distributions were observed in different clinical entities. The case
      fatality rate was 18% overall, but it reached 59% among cases of toxic shock-like
      syndrome. Older age, necrotizing fasciitis, sepsis without focus, pneumonia,
      infection with type M1 or M3 strains, and underlying cardiopulmonary disease were
      associated with fatality. A total of 10,105 patients with noninvasive group A
      streptococcal disease were registered. These patients differed significantly from
      patients with invasive disease with regard to age distribution and primary foci
      of infection.

PMID- 15164260
TI  - Transcatheter embolization of hypogastric artery aneurysms: lessons learned.
AB  - Transcatheter embolization of hypogastric artery aneurysms has become an
      attractive therapeutic alternative for many patients with this difficult lesion.
      Because of the increasing use of stent grafting for treatment of abdominal aortic
      aneurysms, transcatheter embolization of normal-caliber hypogastric arteries has
      become an almost routine procedure, usually accomplished with little morbidity.
      Applying this treatment to aneurysmal hypogastric arteries, however, involves
      greater technical complexity and a significantly higher risk of ischemic
      complications. We present three cases to illustrate the technical challenges of
      hypogastric aneurysm embolization, the potentially devastating ischemic
      complications, and the clinical situations that may predispose to poor outcomes.

PMID- 15164259
TI  - Male chacma baboons (Papio hamadryas ursinus) discriminate loud call contests
      between rivals of different relative ranks.
AB  - Males in multi-male groups of chacma baboons (Papio hamadryas ursinus) in
      Botswana compete for positions in a linear dominance hierarchy. Previous research
      suggests that males treat different categories of rivals differently; competitive
      displays between males of similar rank are more frequent and intense than those
      between disparately ranked males. Here we test whether males also respond
      differently to male-male interactions in which they are not directly involved,
      using playbacks of the loud 'wahoo' calls exchanged between competing males in
      aggressive displays. We played paired sequences of vocal contests between two
      adjacently ranked and two disparately ranked males to ten subjects, half ranking
      below the signalers in the call sequences and half above. Subjects who ranked
      above the two signalers showed stronger responses than lower-ranking subjects.
      Higher-ranking subjects also responded more strongly to sequences involving
      disparately ranked, as opposed to adjacently ranked opponents, suggesting that
      they recognized those individuals' relative ranks. Strong responses to sequences
      between disparately ranked opponents might have occurred either because such
      contests typically involve resources of high fitness value (defense of meat,
      estrous females or infants vulnerable to infanticide) or because they indicate a
      sudden change in one contestant's condition. In contrast, subjects who ranked
      lower than the signalers responded equally strongly to both types of sequences.
      These subjects may have been able to distinguish between the two categories of
      opponents but did not respond differently to them because they had little to lose
      or gain by a rank reversal between males that already ranked higher than they
      did.

PMID- 15164258
TI  - Tuberculous vertebral osteomyelitis in the new millennium: still a diagnostic and
      therapeutic challenge.
AB  - In order to determine the clinical features and current prognosis of tuberculous
      vertebral osteomyelitis, the charts of all patients diagnosed with definite or
      probable tuberculous vertebral osteomyelitis from January 1983 to June 2002 (
      n=78) were reviewed. The mean delay to diagnosis was 6.1 months. Sixty-five
      (83.3%) patients had inflammatory spinal pain, 35 (44.9%) had some neurological
      deficit, and only 27 (34.6%) had fever. Paravertebral, epidural, and psoas
      abscesses were detected in 73.1, 65.4, and 24.4% of the cases, respectively.
      Culture was positive in 48% of the percutaneous biopsies and in 61.7% of the open
      biopsies. After histological findings were included, the diagnostic yield of
      percutaneous biopsies was 68%. Fifty-five (70.5%) patients required surgical
      treatment at some stage of the disease. Although no deaths were directly
      attributable to tuberculous vertebral osteomyelitis and only 5.1% of patients
      relapsed, the mean overall hospital stay was 69.1+/-36.9 days, and 30 (38.5%)
      patients had severe functional sequelae. In conclusion, diagnosis of tuberculous
      vertebral osteomyelitis requires a high degree of suspicion. Percutaneous biopsy
      should be undertaken as soon as possible in any patient with compatible symptoms
      or radiological images in order to initiate suitable therapy.

PMID- 15164261
TI  - An audit of vascular surgical intervention for complications of cardiovascular
      angiography in 2324 patients from a single center.
AB  - This study examines the incidence and outcome of complications requiring surgical
      intervention in a major vascular unit serving interventional radiology and
      interventional cardiology. Between April 2000 and March 2001, 2324 patients
      underwent angiographic examinations (male/female = 1579:745, mean age = 68 years,
      range 45-88). In non-stent patients, a 4-or 5-mm French (4-mm F, 5-mm F) guage
      nonheparinized arterial catheter was used, and in patients requiring stents a 6-
      or 7-mm French guage catheter was used. Pressure was applied to the puncture site
      for up to 6 min. Fifteen complications requiring vascular surgical procedure were
      recorded during in-hospital follow-up (9 males, 6 females). Our early operative
      (30-day) mortality rate was 0.086%. Although the number of major complications
      requiring surgical intervention after interventional or diagnostic cardiovascular
      radiology is diminishing, vigilance in these cases is still required. Where
      possible, a small catheter with a J-shaped guidewire should be used and prolonged
      compression should be brought to bear on the puncture site.

PMID- 15164262
TI  - Infragenicular polytetrafluoroethylene bypass with tapered versus straight
      vascular grafts: results from a prospective multicenter cohort study.
AB  - Both straight and tapered arterial grafts are commonly used for infragenicular
      bypass surgery. Opinions vary considerably regarding the use of each type of
      graft and depend on individual experience, as no trial yet has assessed clinical
      outcomes comparing both groups. We conducted a prospective, multicenter, cohort
      study to analyze results for each graft type. From a total of 81 patients, 50
      underwent infragenicular bypass surgery with straight PTFE prostheses and 31 with
      tapered prostheses in a prospective, multicenter trial. Six different centers for
      vascular surgery took part in the trial. In clinical follow-up at discharge as
      well as 3, 6, 12, 18, 24, and 36 months after revascularization, various
      parameters were evaluated comparing patency rates, limb salvage, and major
      amputation rates. Significant differences were found in limb salvage rates
      between the two groups. Patients receiving a straight graft fared better in this
      regard. Further data suggest that short-term primary patency is also improved in
      straight prostheses. Sixty-four percent of these remained patent after 1 year,
      while only 50% of tapered prostheses were still patent. No differences between
      the groups were found for secondary patency. The advantages of straight
      prostheses seem to be reduction of thrombus formation and intimal hyperplasia.
      Furthermore, it appears that the surgeons participating in this study prefer the
      use of straight prostheses. Even though the group of patients that received
      tapered grafts had slightly more unfavorable preoperative conditions, the data
      still support the superiority of straight vascular grafts. However, prospective
      randomized trials are necessary to evaluate the benefit of different bypass
      designs definitively.

PMID- 15164263
TI  - Hemodynamic changes in stripping operation or saphenofemoral ligation of the
      greater saphenous vein for primary varicose veins.
AB  - The aim of this study was to assess early hemodynamic improvement after a
      stripping operation or saphenofemoral ligation by means of air plethysmography.
      This prospective study assessed 109 limbs of 71 patients treated between May 2000
      and December 2001 for primary varicose veins due to greater saphenous
      insufficiency. Eighty-nine limbs were treated by stripping surgery (stripping
      group), and 20 limbs were treated with saphenofemoral ligation (saphenofemoral
      ligation group). To evaluate venous hemodynamic changes, air plethysmography was
      performed before surgery and 7-14 days after surgery. A significant decrease and
      normalization of the venous filling index and residual volume function was
      observed in the two groups. A decrease in venous volume was observed in the
      ligation group, but the change was not statistically significant. In contrast, a
      significant decrease in venous volume was observed in the stripping group. The
      ejection fraction was not improved in either of the groups. From these results we
      conclude that hydrostatic forces can be controlled by means of a stripping
      operation as well as by saphenofemoral ligation in the early postoperative
      period.

PMID- 15164264
TI  - Role of duplex arteriography as the sole preoperative imaging modality prior to
      lower extremity revascularization surgery in diabetic and renal patients.
AB  - The limitations and complications associated with contrast angiography (CA) prior
      to lower extremity revascularization have led to an increased interest in duplex
      arteriography (DA) as a potential replacement. We report our experience with DA
      in patients with diabetes and/or chronic renal insufficiency (CRI) that would
      particularly benefit from a noninvasive approach to preoperative evaluation of
      the arterial tree. From January 1998 to November 2000, DA was performed in 145
      patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions.
      One hundred twenty-one procedures were performed on 91 patients with diabetes
      alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI
      alone. Patient ages ranged from 36 to 98 years (mean 72 +/- 12 years).
      Indications for surgery were severe claudication in 33 (18%), rest pain in 37
      (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%).
      Optimal inflow and outflow anastomotic sites were selected according to a diagram
      based on DA that included arterial tree imaging from mid-aorta to the pedal
      vessels. Preoperative contrast arteriography was performed in 16 cases (9%)
      because of extremely poor runoff based on DA and limited visualization of outflow
      vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and
      to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed
      the preoperative DA results with the exception of one (0.6%) where the distal
      anastomosis was placed proximal to a significant stenosis requiring an extension
      graft. The use of DA presents a safe and reliable option to prebypass CA for many
      patients with diabetes or CRI. The ease of use and favorable patient outcomes
      achieved by this imaging modality may rival the use of CA for these patients.

PMID- 15164265
TI  - Acute appendicitis-like symptoms as initial presentation of ovarian vein
      thrombosis.
AB  - Postpartum ovarian vein thrombosis is a rare condition, with an incidence rate
      being 1/600 deliveries. It most often arises in the right ovarian vein. A 33-year
      old patient who had had normal vaginal delivery presented with fever, pain in the
      right iliac fossa, and leukocytosis on the sixth day after delivery. An
      antibiotic course was instituted but 3 days later symptoms reappeared. Diagnosis
      of acute appendicitis was made. At surgery through a McBurney incision, a woody
      tumoration consistent with ovarian vein thrombosis was found. Anticoagulation
      therapy with heparin and antibiotics were instituted. Phlebography and color
      Doppler sonography confirmed the presence of thrombosis of both the common
      femoral iliac and inferior vena cava. Fribrolysis with urokinase was performed.
      The patient has remained stable and symptom-free over a 4-year follow-up. Ovarian
      vein thrombosis typically presents with symptoms suggestive of acute
      appendicitis, as was the case in our patient. Color Doppler sonography is the
      favored diagnostic procedure, with CT being a supplementary tool. Surgery is not
      necessary and treatment consists of anticoagulants and antibiotics. Even though
      postpartum ovarian vein thrombosis is rare, early recognition of the condition is
      of paramount importance to institute the adequate treatment and avoid potential
      serious sequelae.

PMID- 15164266
TI  - Pseudoaneurysm of the dorsalis pedis artery causing neurological deficit.
AB  - Pseudoaneurysm of the dorsalis pedis artery is very rare. This case report
      describes a 71-year-old man with an idiopathic aneurysm of the dorsalis pedis
      artery that caused neurological deficit. Surgical resection was performed and his
      symptoms improved.

PMID- 15164267
TI  - What is the future for laparoscopic aortic surgery?

PMID- 15164268
TI  - The first evidence of anaerobic CO oxidation coupled with H2 production by a
      hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent.
AB  - From 24 samples of hydrothermal venting structures collected at the East Pacific
      Rise (13 degrees N), 13 enrichments of coccoid cells were obtained which grew on
      CO, producing H2 and CO2 at 80 degrees C. A hyperthermophilic archaeon capable of
      lithotrophic growth on CO coupled with equimolar production of H2 was isolated.
      Based on its 16S rRNA sequence analysis, this organism was affiliated with the
      genus Thermococcus. Other strains of Thermococcales species ( Pyrococcus
      furiosus, Thermococcus peptonophilus, T. profundus, T. chitonophagus, T.
      stetteri, T. gorgonarius, T. litoralis, and T. pacificus) were shown to be unable
      to grow on CO. Searches in sequence databases failed to reveal deposited
      sequences of genes related to CO metabolism in Thermococcales. Our work provides
      the first evidence of anaerobic CO oxidation coupled with H2 production performed
      by an archaeon as well as the first documented case of lithotrophic growth of a
      Thermococcales representative.

PMID- 15164269
TI  - Geobacillus stearothermophilus V ubiE gene product is involved in the evolution
      of dimethyl telluride in Escherichia coli K-12 cultures amended with potassium
      tellurate but not with potassium tellurite.
AB  - A 3.8-kb fragment of chromosomal DNA of Geobacillus stearothermophilus V cloned
      in pSP72 (p1VH) confers resistance to potassium tellurite (K(2)TeO(3)) and to
      potassium tellurate (K(2)TeO(4)) when the encoded genes are expressed in
      Escherichia coli K-12. The nt sequence of the cloned fragment predicts three ORFs
      of 780, 399, and 600 bp, whose encoded protein products exhibit about 80%
      similarity with the SUMT methyltransferase and the BtuR protein of Bacillus
      megaterium, and with the UbiE methyltransferase of Bacillus anthracis A2012,
      respectively. In addition, E. coli/p1VH cells evolved dimethyl telluride, which
      was released into the headspace gas above liquid cultures when amended with
      K(2)TeO(3) or with K(2)TeO(4). After 48 h of growth in the presence of these
      compounds, a protein of about 25 kDa was found at a significantly higher level
      when crude extracts were analyzed by SDS-PAGE. The N-terminal amino acid (aa)
      sequence of this protein, obtained by Edman degradation, matched the deduced aa
      sequence predicted by the G. stearothermophilus V ubiE gene. This gene was
      amplified by PCR, subcloned in pET21b, and transformed into E. coli JM109(DE3).
      Interestingly, DMTe evolution occurred when these modified cells were grown in
      K(2)TeO(4) - but not in K(2)TeO(3) - amended media. These results may be
      indicative that the two Te oxyanions could be detoxified in the cell by different
      metabolic pathways.

PMID- 15164270
TI  - The soluble [NiFe]-hydrogenase from Ralstonia eutropha contains four cyanides in
      its active site, one of which is responsible for the insensitivity towards
      oxygen.
AB  - Infrared spectra of (15)N-enriched preparations of the soluble cytoplasmic NAD(+)
      reducing [NiFe]-hydrogenase from Ralstonia eutropha are presented. These spectra,
      together with chemical analyses, show that the Ni-Fe active site contains four
      cyanide groups and one carbon monoxide molecule. It is proposed that the active
      site is a (RS)(2)(CN)Ni(micro-RS)(2)Fe(CN)(3)(CO) centre (R=Cys) and that H(2)
      activation solely takes place on nickel. One of the two FMN groups (FMN-a) in the
      enzyme can be reversibly released upon reduction of the enzyme. It is now
      reported that at longer times also one of the cyanide groups, the one proposed to
      be bound to the nickel atom, could be removed from the enzyme. This process was
      irreversible and induced the inhibition of the enzyme activity by oxygen; the
      enzyme remained insensitive to carbon monoxide. The Ni-Fe active site was EPR
      undetectable under all conditions tested. It is concluded that the Ni-bound
      cyanide group is responsible for the oxygen insensitivity of the enzyme.

PMID- 15164271
TI  - Dynamic electrophysiological examination in patients with lumbar spinal stenosis:
      is it useful in clinical practice?
AB  - Neurogenic claudication (NC) is typical of lumbar spinal stenosis (LSS). One
      suspected pathophysiological mechanism underlying NC is intermittent hypoxia of
      cauda equina fibres resulting from venous pooling, which may lead to ischaemic
      nerve conduction failure and to transient clinical and electrophysiological
      changes after exercise. The aim of this study was to evaluate the appearance of
      significant transient electrophysiological abnormalities after walking exercise
      in patients with LSS and to establish the contribution of dynamic
      electrophysiological examination in the differential diagnostics of patients with
      LSS. The study participants were 36 consecutive patients with LSS demonstrated by
      computed tomography (CT). The control groups included, respectively, 28 patients
      with diabetes mellitus and clinically manifested polyneuropathy, and 32 healthy
      volunteers. The LSS patients were divided into four subgroups based on the
      clinical severity of the disease (with respect to the presence or absence of NC
      in the history and pareses on neurological examination). Soleus H-reflex, tibial
      F-wave and motor evoked potentials (MEPs) to abductor hallucis muscle were
      examined in all groups, before and after quantified walking on a treadmill. The
      electrophysiological parameters measured after an exercise treadmill test (ETT)
      in LSS patients and in both control groups were compared with the same parameters
      obtained before ETT. The study shows that the electrophysiological parameters
      reveal minimal but statistically significant changes after walk loading in
      patients with LSS (a prolongation of the minimal latency of the tibial F-wave and
      of the latency of the soleus H-reflex). The changes in these parameters were
      demonstrated not only in patients with NC but also in patients without NC. More
      pronounced changes were found in LSS patients exhibiting chronic lower extremity
      pareses. CONCLUSIONS: From among a large battery of electrophysiological tests,
      only the minimal latency of the tibial F-wave and the latency of the soleus H
      reflex exhibit changes after walk loading in patients with LSS. These are minimal
      but statistically significant. Dynamic electrophysiological examination can
      illustrate the pathophysiology of NC in LSS, but from a practical point of view
      its contribution to the differential diagnostics of LSS or diabetic
      polyneuropathy is limited by an absence of established cut-off values.

PMID- 15164272
TI  - Headache due to an osteochondroma of the axis.
AB  - We reported a case of a 42-year-old man with a 3-year history of headache due to
      a spinal osteochondroma. Repeated neurological evaluation, including EEG studies
      and CT of the cerebrum, revealed no pathology. More recently the patient
      presented with persistent headache and a slight limitation of neck motion. MRI
      studies of the cerebrum including the cervical spine showed a high cervical
      extradural tumor. Additional CT angiography showed a bony tumor suspected of
      being a spinal osteochondroma. An en bloc resection of the tumor was performed;
      histological evaluation confirmed the diagnosis. Immediately after intervention,
      all symptoms disappeared. In most patients with a spinal osteochondroma, the
      lesion causes no symptoms, or symptoms are aspecific. Therefore, there is often a
      significant delay between initial complaints and the diagnosis, as in the current
      case.

PMID- 15164273
TI  - Population genetic structure of an ectomycorrhizal fungus Amanita manginiana in a
      subtropical forest over two years.
AB  - The population genetic structure of the late-stage fungus Amanita manginiana in a
      natural forest in Dujiangyan, southwest China was examined over two years using
      inter-simple sequence repeat (ISSR) markers. Seven ISSR primers were used and 170
      bands were obtained in this population: 134/160 and 135/153 bands were
      polymorphic for sporocarps of 2001 and 2002, respectively. Each sporocarp
      represented a single genet in 2001 and 2002, and no identical genets were found
      between the two years. The results of genetic similarity comparison, using
      unweighted pair group method with arithmetic means, and analysis of molecular
      variance, indicated that although genetic variances were mainly within
      individuals of the same year the genetic variance between years was statistically
      significant (P<0.001). Relationships between genetic similarity and spatial
      distance of pairwise sporocarps were also found to be different in the two years.
      The differences in genetic structure and genetic similarity between individuals
      of the two years implied that the sporocarps were not likely to be derived from
      continuous generations, i.e., the sporocarps collected in 2002 were not developed
      from sexual spores dispersed by sporocarps of 2001. We suggest that the life
      cycle traits of ectomycorrhizal (ECM) fungi should be considered in genetic
      studies on ECM fungal populations.

PMID- 15164274
TI  - Rapid growth and early flowering in an invasive plant, purple loosestrife (
      Lythrum salicaria L.) during an El Nino spring.
AB  - Phenological shifts may play a role in the success of invasive species,
      especially in association with climatic variability. We studied the response of a
      North American population of the invasive plant, Lythrum salicaria L., to changes
      in local climate associated with the El Nino/Southern Oscillation Event (ENSO) of
      1997-1998. For L. salicaria plants at two wetland sites near North Bay, Ontario,
      Canada, we made weekly observations of flowering phenology and monthly
      measurements of aboveground biomass during the 1997 and 1998 growing seasons
      (April-October). Reproductive output was measured as cumulative length and
      biomass of inflorescences at the end of the growing season. Temperature and
      precipitation during the 1997 growing season were typical for the region and
      provided good baseline data for comparison to the full effects of the ENSO event
      in 1998, which increased spring temperatures and reduced precipitation in the
      study area. In response to these conditions, populations of L. salicaria began to
      flower 14 days earlier (Julian day = 181 +/- 10) in 1998 than in 1997 (Julian day
      = 195 +/- 12), and accumulated more aboveground biomass early in the growing
      season (P < 0.05). However, by the end of the growing season, there were no
      significant differences between years in aboveground biomass or total
      inflorescence lengths, and senescence of plants occurred at similar times for
      both growing seasons. Advances in spring phenology during ENSO events offer
      several potential advantages to L. salicaria, and could have a significant impact
      on biological control programs initiated for this species in North America.

PMID- 15164275
TI  - [Use of the World Health Organization guidelines on cancer pain relief before
      referral to a specialized pain service].
AB  - In 1986 the World Health Organization (WHO) released guidelines for cancer pain
      relief. Since then, several controlled studies on effectiveness and
      practicability of these guidelines have been published. Various authors described
      inadequate use of these guidelines. We analysed, whether the pain medication of
      160 cancer patients referred to the anesthesiological pain clinic at the
      university hospital of Vienna corresponded to the WHO guidelines or not. Adequacy
      of pain treatment was assessed using the pain management index (PMI). Multiple
      criteria were chosen to assess the conformity of the treatment with the
      guidelines. Furthermore we studied the effect of a strict use of the WHO
      guidelines in these patients. The average pain intensity of the referred patients
      was 75 mm (VAS). Negative PMI scores, indicating inadequate pain therapy, were
      found in 39 % of cases. A violation of the rules was found in 38% of the therapy
      schedules. Pain medication was then modified by switching to fixed time
      intervals, escalation of the steps of the WHO ladder, increasing the dosage or
      treating neuropathic pain with adjuvant drugs. Two weeks later the average pain
      score of the patients was reduced to 27 mm (VAS). At that time 72% of the
      patients quoted an adequate reduction of pain. Inadequate knowledge or disregard
      of the WHO guidelines for cancer pain relief are common and result in unnecessary
      and prolonged suffering in these patients.

PMID- 15164276
TI  - Characterizing the "gold standard" image for laparoscopic surgery.
AB  - BACKGROUND: The term "gold standard" is often used to describe preferred display
      devices, frequently without substantiating evidence. A meaningful and objective
      measure of display quality for endoscopic surgery is required. METHODS: Typical
      colors from five tissue types were arranged in a striped pattern and displayed on
      four devices: a medical-grade cathode ray tube monitor, a liquid crystal display,
      a digital light projection display, and an obsolete cathode ray tube (CRT)
      monitor. The breadth and color contrast of the stripes were adjusted until the
      patterns became indiscernible to 12 subjects. The data provide a discernibility
      threshold. RESULTS: The liquid crystal display (LCD) monitor provided the best
      image. The medical grade and obsolete CRTs were second and third, respectively,
      and the projection display provided the most inferior image. CONCLUSIONS: A
      meaningful and relevant measurement of image display quality for laparoscopic
      surgery based on the discernibility threshold is provided. Of the devices tested,
      the LCD is the best in terms of image, although the CRT may be preferred at off
      axis viewing angles. The projection system, however, offers compensatory
      ergonomic advantages.

PMID- 15164277
TI  - Outcome in laparoscopic management of persistent adnexal mass during the second
      trimester of pregnancy.
AB  - BACKGROUND: This study evaluated the safety of laparoscopic management for
      persistent adnexal mass in the second trimester of pregnancy. METHODS: Between
      April 1994 and March 2003, 67 consecutive women underwent laparoscopic removal of
      adnexal masses that had persisted into the second trimester of pregnancy in an
      academic tertiary referral center. Operative complications, pregnancy, and labor
      outcomes were evaluated. RESULTS: The median gestation was 10.5 weeks (range, 5
      25 weeks) at diagnosis and 16 weeks (range, 12-25 weeks) at the time of
      operation. Only two women required for conversion to laparotomy. Cystectomy was
      performed for 55 women, oophorectomy for 9 women and fenestration in 3 women.
      There were no intraoperative complications or major postoperative complications.
      No women were given tocolytic therapy, and none experienced uterine contractions.
      There was one spontaneous abortion 6 weeks after the operation, and one patent
      was lost to follow up. Of the remaining 65 women, the median gestation at
      delivery was 39 weeks (range, 33-42 weeks), and the median birthweight was 3,160
      g (range, 2,220-4,200 g). CONCLUSIONS: Laparosocpic surgery for persistent
      adnexal masses in the second trimester of pregnancy is safe when performed by
      experienced surgeons.

PMID- 15164278
TI  - Emergent laparoscopic repair of incarcerated incisional and ventral hernia.
AB  - BACKGROUND: The role of laparoscopy in the repair of incarcerated incisional or
      ventral hernia is not yet established. This presentation reviews the authors'
      experience with patients who underwent laparoscopic surgery in presence of
      incarceration. METHODS: Patients who had surgery during the years 1997 to 2001
      were included in the study. All patients underwent surgery immediately after
      their admission. In all cases, Gore-Tex Dual Mesh was used. RESULTS: The review
      included 25 patients (21 women and 4 men). Ten of these patients (40%) had
      undergone at least one earlier repair, and one patient (4%) underwent conversion
      to open repair because of small bowel injury. The mean operation time was 63 min
      (range, 15-20 min). The median postoperative hospital stay was 3.2 days (range, 2
      7 days). There were no noteworthy postoperative complications. During the follow
      up period, no patient experienced recurrent hernia. CONCLUSIONS: The authors'
      current has experience demonstrated that laparoscopic repair is feasible and can
      be attempted for patients presenting with incarcerated incisional or ventral
      hernia.

PMID- 15164279
TI  - Impact of video colonoscopy on stage and outcome of patients with symptomatic
      colorectal cancer.
AB  - BACKGROUND: Double-contrast barium enema still is regarded by many as the
      investigation of choice for patients with large bowel symptoms. The aim of this
      study was to compare the stage and outcome of patients with colorectal cancer
      diagnosed by video colonoscopy (VC) and barium enema (BE) in a single
      institution. METHODS: Between July 1997 and December 2001, data were gathered
      prospectively in a series of 489 patients presenting consecutively with
      symptomatic colorectal cancer. Selection of patients for either VC or BE
      investigation was made by the clinician who examined the patient in the clinic.
      Of the 489 patients, 82 were excluded because they presented acutely or other
      methods were used for the diagnosis. RESULTS: A diagnosis of colorectal cancer
      was determined by VC for 292 patients and by BE for 115 patients. The patients in
      both groups were similar in terms of age, gender, and site of disease. Stage 1
      disease (T1/2NO) was diagnosed for 87 (29.8%) patients in the VC group, as
      compared with 10 (8.7%) in the BE group (p < 0.0001). Early colorectal cancer
      (T1) was diagnosed for 43 patients in the VC group as compared to 1 patient in
      the BE group (p < 0.0001). During a median follow-up period of 33 months, 8.2% of
      the patients in the VC group had experienced recurrence after curative resection,
      as compared with 17.4% of the patients in the BE group p = 0.018). Freedom from
      disease (p = 0.02) and overall survival (p = 0.03) were significantly increased
      in the VC group. CONCLUSIONS: Videocolonoscopy used as the investigation of
      choice for patients with large bowel symptoms detects colorectal cancer at an
      earlier stage and has a significant impact on the outcome for this condition.

PMID- 15164280
TI  - Anesthesiological hazards during laparoscopic transhiatal esophageal resection: a
      case control study of the laparoscopic-assisted vs the conventional approach.
AB  - BACKGROUND: Interest for minimal invasive approach of esophagus resection is
      increasing. Today, a minimally invasive transhiatal esophagectomy is possible and
      is accepted widespread. Since cardiopulmonary changes during laparoscopic
      dissection of the mediastinum has not been studied yet we assessed the
      anesthesiological consequences of pneumothorax during laparoscopic mediastinal
      dissection. METHODS: In this case control study, 25 laparoscopically assisted
      transhiatal espohagus resections were compared with a control group consisting of
      20 open transhiatal esophagus resections. Patient characteristics and
      intraoperative haemodynamic, respiratory, and ventilatory parameters were
      assessed. RESULTS: The laparoscopic assisted procedure was performed successfully
      in 12 of the 20 patients. The duration of the laparoscopic assisted procedure,
      compared to the open group was significantly longer (p<0.05). Intraoperative
      blood loss was significantly less in the laparoscopic group (p<0.05). Mediastinal
      dissection resulted in entry of the pleura in 84% of the open and 93% of the
      laparoscopic assisted procedure. Carbonedioxide pneumothorax resulted in
      increased end-tidal CO2)and airway pressure levels and decreased lung compliance.
      Airway pressure showed a significant difference between the groups (p<0.05).
      Hemodynamic parameters did not differ between groups significantly. There were no
      differences in postoperative cardiopulmonary complications. CONCLUSIONS:
      Laparoscopic assisted transhiatal esophagectomy is a safe procedure and has no
      increased risk of postoperative cardiopulmonary complications compared to thr
      conventional approach. The anesthesiologist and the surgeon must be aware of the
      potential risk of pleural injury to manage cardiopulmonary compromises and
      minimize complications.

PMID- 15164281
TI  - Manual robot assisted endoscopic suturing: time-action analysis in an
      experimental model.
AB  - BACKGROUND: Robotic surgery systems were introduced to overcome the disadvantages
      of endoscopic surgery. The goal of this study was to assess whether robot
      assistance could support endoscopic surgeons in performing a complex endoscopic
      task. METHODS: Five experienced endoscopic surgeons performed end-to-end
      anastomosis on post-mortem porcine small intestine. The procedure was performed
      both with standard endoscopic techniques and with robotic assistance (da Vinci
      system, Intuitive Surgical, Sunny vale, CA). It was performed in three different
      working directions with a horizontal, vertical, and diagonal position of the
      bowel. Anastomosis time, number of stitches, knots, time per stitch, suture
      ruptures, and the number of stitch errors were recorded. Also, an action analysis
      was performed. RESULTS: Anastomosis time, number of stitches, and the number of
      knots did not differ significantly between the two groups. The time needed per
      stitch was significantly shorter with robot assistance (81.4 sec/stitch vs 95.9
      sec/stitch, p = 0.005). More suture ruptures occurred in the robot group (0 (0-2)
      vs 0 (0-0), p = 0.003). In the standard group more stitch errors were found (2 (0
      5) vs 0 (0-3), p = 0.017). These results were comparable for three different
      working directions. The action analysis, however, showed significant benefits of
      robotic assistance. The benefits were greatest in a vertical bowel position.
      CONCLUSION: Robot assistance might offer added value to experienced endoscopic
      surgeons in the performance of a small-bowel anastomosis in an experimental
      setup, even though total anastomosis time could not be demonstrated to be shorter
      and some suture tears occurred due to the lack of force feedback.

PMID- 15164282
TI  - Fiber-optic bronchoscopic classification of inhalation injury: prediction of
      acute lung injury.
AB  - BACKGROUND: Fiber-optic bronchoscopy is widely used for the early diagnosis of
      inhalation injury. However, there is no current bronchoscopic classification of
      inhalation injury for the prediction of acute lung injury (ALI). Our goal was to
      devise such a classification. METHODS: Between February 1993 and January 2002,
      167 patients with highly suspicious inhalation injuries were collected. All
      patients received fiber-optic bronchoscopy within 24 h after their accident. In
      total, 108 patients were diagnosed as positive under direct inspection. The
      patients were divided into three groups (G(1), G(2), and G(3)) according to the
      depth of mucosal damage. Six patients were found to be positive by biopsy and
      were assigned to group Gb. Of these 114 positive cases, 27 developed ALI.
      Meanwhile, 53 patients were diagnosed as negative; these patients were assigned
      to group G(0). RESULTS: After analysis, the following results were noted: G(0) (n
      = 53), two ALI (3.8%); G(1) (n = 49), two ALI (4%); G(2) (n = 46), 15 ALI (33%);
      G(3)(n = 13),10 ALI (77%); Gb (n = 6), no ALI. We discovered that the deeper the
      mucosal injuries, the higher the rate of ALI. There were no deaths related to the
      procedure. CONCLUSIONS: Fiber-optic bronchoscopy is a safe and effective method
      for the early diagnosis of inhalation injuries. Also, it is a good predictor of
      ALL. We hope that in the near future, this classification will serve as a
      treatment guideline for the early prevention of ALI. The more severe the damage,
      the more alert clinicians need to be to improve the patient's chances for
      survival.

PMID- 15164284
TI  - Litter decomposition in moist acidic and non-acidic tundra with different glacial
      histories.
AB  - Plant species composition is a potentially important source of variation in soil
      processes, including decomposition rates. We compared litter decomposition in two
      common and compositionally distinct tundra vegetation types in the northern
      foothills of the Brooks Range, Alaska: moist acidic tundra (soil pH 3-4), which
      occurs primarily on older landscapes, and moist non-acidic tundra (soil pH 6-7),
      which occurs primarily on landscapes with a more recent history of glaciation and
      has higher graminoid and forb abundance and lower woody shrub abundance than
      acidic tundra. To separate the influence of plant community composition from that
      of the soil environment, we decomposed the same nine substrates at a moist acidic
      and a moist non-acidic site located less than 2 km apart. Substrates included
      leaf litter of the dominant species in each growth form (graminoid, deciduous
      shrub, evergreen shrub, forb, moss) as well as woody stems of the deciduous shrub
      Betula nana. Then, we estimated above-ground community-level decomposition by
      weighting the decay rate of each species in the community by its proportional
      contribution to overall above-ground net primary production (ANPP). In contrast
      to our expectations, community-level decomposition rates estimated using the site
      average decay rate for each substrate were similar between the two sites, likely
      because growth forms differed little in their leaf litter decay. By contrast,
      when site-specific decay rates were used to estimate community-level
      decomposition, it was nearly twice as fast at the older, moist acidic tundra site
      because most substrates decayed faster at that site, indicating a more favorable
      environment for decomposition in acidic tundra. Site differences in soil moisture
      and temperature could not explain site differences in decomposition. However,
      higher soil N availability at the moist acidic tundra may have contributed to
      faster decomposition since, in a separate experiment, fertilization with N
      stimulated decomposition of a common substrate at both sites. In addition, lower
      pH in acidic tundra may promote greater abundance of soil fungi, perhaps
      explaining faster decomposition rates at that site. In summary, the large
      differences in plant species composition between moist acidic and non-acidic
      tundra are likely to not contribute to site differences in decomposition.
      Nevertheless, decomposition is much more rapid in moist acidic tundra. Thus,
      landscape age and associated differences in soil pH and nutrient availability are
      important sources of variation in decomposition rate in upland Alaskan tundra.

PMID- 15164283
TI  - Endoscopic palliative treatment for esophageal and gastric cancer: techniques,
      complications, and survival in a population-based cohort of 948 patients.
AB  - BACKGROUND: Under the auspices of the Scottish Audit of Gastric and Esophageal
      Cancer, we investigated treatment techniques, complications, and survival in a
      population-based cohort of patients undergoing endoscopic palliative therapy for
      esophageal or gastric cancer. METHODS: A total of 948 patients undergoing
      endoscopic palliative therapy were identified prospectively and followed for a
      minimum of 1 year. RESULTS: Expandable metal stent placement (506 patients) and
      LASER (117 patients) were the most frequently used treatment options. Stent
      placement was more common for grade 3 or 4 dysphagia. Delivery of endoscopic
      palliative therapy varied by region of residence (from 18% to 38% of patients, p
      < 0.001) but not by deprivation category. Complications were recorded in 16% of
      patients (155 of 948). Overall survival was 40% (95% confidence interval [CI], 36
      43) at 6 months, 17% (95% CI, 14-19) at 12 months, and 10% (95% CI, 8-12%) at 18
      months. CONCLUSIONS: These data define the reality of endoscopic palliative
      therapy for patients with advanced esophageal or gastric cancer and provide a
      baseline against which future improvements in care can be measured.

PMID- 15164287
TI  - Immunolocalization of a plant glutathione peroxidase-like protein.
AB  - We report on the localization of GPXle-1, a plant glutathione peroxidase (GPX)
      like protein, in the internode of Lycopersicon esculentum Mill. GPXle-1 was
      detected in the cytoplasm near to the plasma membrane of trichomes, in the wall
      of collenchyma and in both the cytoplasm and wall of vascular tissues. GPXle-1
      was not found in the epidermis or parenchyma. After mechanical stimulation, a
      change in its cell distribution was recorded. In stimulated plants, GPXle-1 was
      detected throughout the cytoplasm in the epidermis, collenchyma and cortical
      parenchyma.

PMID- 15164285
TI  - Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from
      the ACE allele with deletion.
AB  - The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin
      converting enzyme (ACE) gene is involved in the development of cardiovascular
      diseases. We compared the ACE mRNA expression originating from the allele with a
      deletion (D allele) and that from the allele with an insertion (I allele) in
      human white blood cells from ID heterozygotes. We identified the mRNA from the I
      allele by using the G2215A polymorphism that lies in exon 15 and that was linked
      to the I/D polymorphism. RNA samples were obtained from 12 healthy heterozygotes
      of both I/D and G2215A, and every insertion was shown to be linked to 2215G. ACE
      mRNA was amplified by the reverse transcription/polymerase chain reaction (RT
      PCR) method with an end-labeled antisense primer. The PCR products were digested
      with HaeII and separated by electrophoresis, and the relative radioactivities of
      the 2215A and 2215G bands were measured on an auto-image analyzer. The results
      showed that, in every cases, the intensity of the 2215A product (D allele origin)
      was higher than that of the 2215G product (I allele origin). The mean ratio of
      2215A to 2215G was 1.79 (1.11-2.62). Thus, the D allele leads to higher
      expression of the ACE mRNA and may affect the renin-angiotensin system in local
      regions.

PMID- 15164288
TI  - The tall-cell variant of papillary thyroid carcinoma: a multivariate analysis of
      clinical risk factors.
AB  - BACKGROUND: The biological behaviour of the tall-cell variant (TCV) of papillary
      thyroid carcinoma (PTC) remains to be clarified in a multivariate analysis that
      controls for all relevant clinicopathological parameters. PATIENTS AND METHODS: A
      retrospective analysis was carried out of 332 consecutive PTC patients operated
      on at a university hospital between November 1994 and February 2003. RESULTS: A
      total of 16 TCV tumours (4.8%) was identified among the 332 PTC patients. Nodal
      and (predominantly pulmonary) distant metastases were identified at surgery in,
      respectively, 50% and 31% of TCV tumours. On univariate analysis, only the
      association between the TCV and distant metastasis retained statistical
      significance after adjustment for multiple testing. On multivariate logistic
      regression analysis, the presence of distant metastasis increased more than
      fourfold [odds ratio (OR) 4.2] the chance of having the TCV of PTC, with controls
      for extrathyroidal extension, nodal metastasis, operation status, patient gender,
      categorized patient age, and categorized primary tumour diameter. CONCLUSION: The
      increased risk of distant metastasis associated with the TCV morphology of PTC
      warrants an extensive post-operative search for distant metastasis to facilitate
      early diagnosis and treatment of tumour deposits in distant organs.

PMID- 15164290
TI  - [How good are clinical investigative procedures for diagnosing meniscus
      lesions?].
AB  - AIM: The purpose of this study was to evaluate different clinical meniscus tests.
      METHOD: During 13 months we evaluated 64 patients with a suspected meniscus
      lesion in a prospective study. The age ranged from 16 to 76 years (average: 38.5
      years). 66 % were male patients. Between the clinical examination and the
      arthroscopy there was no additional trauma to the knee. All patients were
      clinically examined in a standard manner by two independent orthopaedic surgeons.
      Clinical findings of the menisci were documented according to 12 well-described
      and commonly used meniscus tests. The arthroscopy was performed by a single
      surgeon who was not aware of the results of the clinical examination. This
      surgeon documented the intraarticular findings in a standardized operating
      report. A meniscus lesion/degeneration was documented when this was evident
      either by inspection or by palpation. RESULTS: The results showed either clinical
      meniscus tests with a high specificity and a low sensitivity or tests with a high
      sensitivity, but only a low specificity. We were not able to identify meniscus
      tests which showed both a high sensitivity and a high specificity. CLINICAL
      RELEVANCE: Even with access to MRI the clinical findings in knee joint with
      injured menisci still have a high diagnostic value. However, it seems to be
      necessary to combine different tests.

PMID- 15164289
TI  - Exposure to glycol ethers in a population of French men evaluated by measurement
      of urinary alkoxycarboxylic acids.
AB  - OBJECTIVES: Glycol ethers are solvents that are present in a large number of
      products used commercially and domestically. During recent years, ethylene glycol
      ether derivatives, in particular ethylene glycol methyl ether and ethylene glycol
      ethyl ether, have been progressively replaced by propylene glycol ether
      derivatives, which are less toxic. The aim of this study was to estimate the
      level of exposure to glycol ethers in a sample population of French men employed
      by the Paris Municipality by measuring the amount of alkoxycarboxylic acid
      metabolites in their urine. METHODS: Urine samples were collected at the end of
      two different working weeks from 109 men, 54 of whom were judged to be
      occupationally exposed to glycol ether-containing products. Five alkoxyacetic
      acids (methoxyacetic, ethoxyacetic, n-propoxyacetic, phenoxyacetic, butoxyacetic
      acids) from ethylene glycol derivatives, and one alkoxypropionic acid (2
      methoxypropionic) from a propylene glycol derivative, were simultaneously
      analysed by gas chromatography coupled to electron-capture detection. RESULTS: 2
      Methoxypropionic was the most frequently found alkoxycarboxylic acid. The
      concentration of this metabolite reached 5.6 mmol/mol creatinine. The second most
      common alkoxycarboxylic acid was phenoxyacetic (up to 2.3 mmol/mol creatinine).
      The concentrations of the other alkoxycarboxylic acids were less than 1 mmol/mol
      creatinine. Although the concentration of alkoxycarboxylic acids was higher among
      men occupationally exposed to glycol ether-containing products than among
      unexposed men, the difference was significant only for butoxyacetic acid.
      CONCLUSIONS: Our data suggest that the use and exposure levels of glycol ethers
      have qualitatively and quantitatively changed dramatically over recent years.
      Particular attention should be paid in the future to alkoxypropionic acids
      derived from minor isomers of propylene glycol ether derivatives.

PMID- 15164291
TI  - [MRI evaluation of meniscal movement and deformation in vivo under load bearing
      condition].
AB  - AIM: The aim of this experimental study was a quantitative evaluation of meniscal
      movement and deformation in vivo under load bearing conditions. METHODS: Sagittal
      T1-weighted MRI pictures of 15 healty knees were evaluated. The subjects were
      placed in an open MRI, that enabled measurements under load bearing and in
      different flexion grades. Series of pictures of the medial and lateral meniscus
      without load, with half and full body weight load and in full extension and 30
      degrees flexion were taken. Two examiners measured twice the height of the
      posterior horn, and the inner and outer distance between the anterior and
      posterior horns of the menisci. RESULTS: The height of the posterior horns of the
      medial and lateral menisci decreased with increasing load. The inner and outer
      distance increased with load, the inner distance more than the outer, resulting
      in a compression of the periphery. Increase of flexion from 0 degrees to 30
      degrees significantly influenced only the outer distance of both menisci.
      CONCLUSION: This method can be used in future to functionally evaluate the
      postoperative result after meniscus saving or replacing therapies. The
      compression of meniscal periphery from the inside to the outside under load in
      full extension allows early postoperative mobilisation after meniscal sutures.

PMID- 15164292
TI  - [How reliable are data from 3d-gait analysis].
AB  - AIM: The aim of the present study was to collect preliminary data to determine
      the test-retest reliability in healthy subjects using 3-dimensional computerised
      gait analysis. METHOD: Ten healthy subjects (6 females, 4 males) were tested
      using a 3-dimensional computerized gait analysis system (VICON 512, Oxford
      Metrics). There were two trials within a 2-hour period in which kinetic,
      kinematic and time-distance data were collected. Markers were removed after the
      first trial and reapplied for the second trial and Pearson's correlation
      coefficients were calculated. RESULTS: The correlation coefficients were all
      positive and high for time-distance (r = 0.86-0.99), sagittal plane kinematics (r
      = 0.86-0.98) and power (r = 0.90-0.98) parameters, indicating excellent
      reliability of these measures. Correlation coefficients for frontal and
      transverse plane kinematics were lower (r = 0.59-0.89). The lowest correlation
      coefficient values were obtained for transverse plane measures at the hip joint
      indicating poor reliability of this measure in healthy subjects. CONCLUSION: The
      results suggest excellent test-retest reliability using 3-dimensional
      computerized gait analysis, especially in the sagittal plane. Therefore this
      method is a very valuable tool in the analysis as well as in the outcome
      evaluation of conservative and operative procedures in movement disorders

PMID- 15164293
TI  - [Injuries in Olympic handball tournaments: a video analysis].
AB  - INTRODUCTION: The aim of the study was to achieve injury situations in European
      team handball with a video based method. METHODS: A video tape containing 59
      injuries of an Olympic handball tournament were analyzed by two observers (sports
      scientist, orthopaedic surgeon). The analysis was based on a method previously
      published by Teitz, which was developed to analyze ACL-injuries. The parameters
      body region, field position, contact/non-contact, offense/defense, field
      player/goal keeper were mainly used. RESULTS: The most injuries were localized at
      the head (N = 20), the lower limb (N = 15), thorax and abdomen (N = 9) and the
      upper limb (N = 9). Concerning the field, the most injuries were in the midfield
      (N = 20), followed by the left (N = 13) and right (N = 9) outside position. The
      injured players were mostly in the offense (84 %), and in the majority of cases
      the field players were affected (97 %). 86 % of the injuries accomplished by
      contact. CONCLUSION: The head has a high risk, predominantly of contact injury.
      Contact-injuries could only be reduced by strict decisions of the referees. Non
      contact injuries should be prevented by a special coordinative training.

PMID- 15164294
TI  - [Injuries- and frequency of complaints in competitive tennis- and leisure
      sports].
AB  - Tennis is one of the most popular sporting activities in Germany and worldwide.
      According to this fact injuries and complaints associated with this sport are
      common in tennis players. Here a retrospective analysis was undertaken in 60
      tennis players with and 50 tennis players without tournament experience. Injuries
      were seen in all players. The most common lesions were blisters, sunburn and
      abrasions (65.5 %) followed by cramps (51.8 %), strains (35.5 %) and sprains
      (25.5 %). More severe injuries like meniscal lesions or ruptures of the cruciate-
      and ankle-ligaments or the achilles tendon were found in 2 % to 4 %. Fractures
      were not seen in this study. The majority of tennis injuries occurred in the
      lower extremity (182 vs. 62) whereas chronic complaints domain in the upper
      extremity (38/91). Most of the injuries and complaints have been treated
      conservatively with good results. Only 3.3 % of all acute and 2.2 % of the
      chronic lesions were treated by surgical intervention.

PMID- 15164296
TI  - [Disturbed eating behaviour among high school and university students].
AB  - To develop suitable preventive programs for eating disorders, it is important to
      examine the prevalence and severity of disturbed eating behaviour in the
      corresponding risk population as well as to investigate the conditions that might
      explain their origin and further progression. Based upon this background 736
      female and male high school and university students from Eastern and Western
      parts of Germany were examined. Height and weight were measured objectively. In
      accordance with the study of Buddeberg-Fischer three groups were defined
      depending on the total score in the Eating Attitudes Test. 28.5 % of the women
      and 12.6 % of the men revealed impaired eating behaviour with female high school
      students being specifically affected (35.3 %). With an increasing impairment,
      women more often used methods to regulate their weight like diets, restrained
      eating, or drugs. Participants with disordered eating behaviour were also more
      likely to show higher scores on the subscales of the Eating Disorders Inventory
      and a distorted body perception. The feeling of being overweight showed a
      correlation with the severity of the disturbed eating. With increasing eating
      problems the correspondence between the real existing BMI and the subjective
      estimation of the weight decreased significantly. The results of this study
      clearly demonstrate the high prevalence of disturbed eating behaviour and
      concerns about weight among female adolescents and young adults. Female high
      school students should be a special target group for the application of
      preventive programs. The reported use of drugs in order to lose weight should be
      discussed more explicitly.

PMID- 15164295
TI  - [Effects of sports and media consumption on the trunk muscle strength, posture
      and flexibility of the spine in 12- to 14- year-old adolescents].
AB  - INTRODUCTION: Back pain and posture deficits get more common in childhood and
      adolescents. Lack of movement, insufficient physical education and high amounts
      of TV and PC are known as risk factors for chronic low back pain in later life.
      METHODS: In a cross-sectional study, trunk muscle strength, posture and spinal
      flexibility were assessed in 200 untrained schoolchildren (117 girls, 83 boys).
      Independent variables, collected by a standardized questionnaire: age, height,
      weight, gender, weekly scope of TV, PC and sports (conditional, conditional
      coordinative, coordinative). DEPENDENT VARIABLES: spinal parameter, tested by the
      Zebris CMS-System and IPN Back Check. OUTCOMES: PC and TV-consumption had
      negative effects on the spinal parameter, whereas esp. conditional-coordinative
      sports correlated positively. DISCUSSION: For general health and preventive
      reasons, children need a daily minimum of 30 minutes of movement. Conditional
      coordinative sports are suited best because of their multifactorial load.

PMID- 15164297
TI  - [Journal statistics - information for authors].

PMID- 15164298
TI  - [Inter-session-processes].
AB  - We do not know much about how patients internalize, remember or use
      psychotherapeutic experiences between psychotherapy sessions and how they use
      them for change. What happens with in-session-experiences after a session ("inter
      session-process") is of main importance for outcome. The inter-session-process
      describes the work on psychotherapy between sessions. Although inter-session
      processes are a central element connecting psychotherapy process and outcome,
      they remain a neglected area of research. Previous studies examined individual
      outpatient settings only. This paper gives an overview over theory, instruments
      for measurement, previous studies and relevance of inter-session-processes for
      the field of psychotherapy research.

PMID- 15164299
TI  - [Mother-infant interaction and adrenocortical reactivity in infancy].
AB  - The aim of this study was to examine the relationship between maternal
      reactivity/sensitivity when interacting with her child and the adrenocortical
      reactivity of the child in a distressing situation. Based on former results
      reported in the literature a negative relationship was hypothesized. 20 mother
      child-dyads were examined when babies were four and 23 dyads when babies were
      eight months old. At each age data were collected in two settings (laboratory and
      at home). In both settings the interaction between mother and child was observed.
      Additionally the adrenocortical reactivity of the baby was examined in a separate
      situation of induced stress. At the age of four months the expected negative
      relationship between maternal reactivity/sensitivity and the adrenocortical
      response was found to be significant. When babies were eight months this
      relationship was much weaker and not statistically significant. The present
      results are in congruence with formerly reported data from the literature.

PMID- 15164300
TI  - [Synergetics of hypnoid relaxation].
AB  - The Autogenic Training (AT) is a well established relaxation technique and
      psychotherapy tool. We report the use of nonlinear routines, the Multi-scaled
      Time-Frequency-Distribution (mTFD) for the graphical display of vegetative
      rhythms, and Post-Event-Scan (PES) for the direct visual identification of
      coupling between physiological subsystems. Applying these methods to time series
      of respiration, arterial blood pressure, and cutaneous forehead blood content
      fluctuations in controls (n = 11) or AT-experts (ATE, n = 11) induced psychomotor
      drive reduction during orthostatic stress allowed the instantaneous
      identification of a 0.15 Hz-rhythm. This rhythm prevailed in ATE significantly
      longer resulting a significantly robust 1 : 1 coupling between cutaneous blood
      content fluctuations and respiration. Consequently, we hypothesize that the "0.15
      Hz-rhythm" in the cutaneous blood content fluctuations described previously which
      was associated with the subjective experience of profound psychomotor relaxation
      reflects an order-order transition in peripheral signals of central nervous
      origin. Results produced with the aid of these analytic tools support the
      efficacy of the AT induced, synergetic relaxation response.

PMID- 15164303
TI  - Gene expression studies in leiomyomata: new directions for research.
AB  - Uterine leiomyomata (fibroids) are a leading women's health problem, resulting in
      significant morbidity and surgical intervention. As benign clonal tumors,
      leiomyomata also represent a target well suited to molecular analysis. Familial
      studies and genetic syndromes featuring leiomyomata provide compelling evidence
      that genetic alterations may cause fibroid development, but the specific genes
      involved in leiomyoma development have not been identified. Microarrays permit
      simultaneous comparison of the relative expression of thousands of genes, thereby
      highlighting specific genes that may play a role in the development of
      leiomyomata. Microarray studies conducted by several laboratories have identified
      candidate genes. However, few gene products have been confirmed with alternative
      experimental approaches. The objective of this article is to focus on the
      insights provided by microarray studies investigating leiomyoma development. Such
      studies suggest that although hormonal control of leiomyoma growth is observed,
      there are other critical pathways involved in development of the leiomyoma cell
      phenotype that warrant investigation. In particular, expression of extracellular
      matrix genes in leiomyomata is deranged and such genes represent potential novel
      targets for therapy.

PMID- 15164304
TI  - Apoptosis in human uterine leiomyomas.
AB  - Human uterine leiomyomas (fibroids) are benign neoplasms that typically occur in
      reproductive age and perimenopausal women. These tumors pose a significant and
      costly health concern for numerous women throughout the world. Alternative
      therapies are few, with hysterectomy being the treatment of choice by many
      physicians. There is a growing body of evidence suggesting that the development
      of leiomyomas may be influenced by numerous factors including genetic,
      environmental, and hormonal influences resulting in a possible failure of any
      number of apoptotic pathways. Understanding the role apoptosis plays in the
      normal regression of nascent myometrial tissue and how this failure may influence
      leiomyoma tumor growth may provide a better understanding of how to develop
      effective and less invasive treatment modalities for this disease. The following
      review attempts to highlight what is currently known about apoptosis in
      leiomyomas as compared with the normal myometrium and where future research is
      needed.

PMID- 15164305
TI  - Treatment strategies for uterine leiomyoma: the role of hormonal modulation.
AB  - Uterine leiomyomas are the most common gynecological tumors and are a significant
      health concern for many women. Although the exact etiology of these tumors is
      unknown, epidemiological and experimental animal studies have established a role
      for ovarian hormones in the pathogenesis of this disease. Current treatment
      regimens for symptomatic tumors primarily require surgical intervention. However,
      a major emphasis of leiomyoma research involves understanding how hormones
      regulate tumor growth to target the hormonal dependence of these tumors with new
      therapeutic strategies. Gonadotropin-releasing hormone agonists that block
      hormone production and induce a hypoestrogenic milieu can be utilized as adjuvant
      therapy; however, these drugs do little to reduce tumor cellularity, and their
      negative impact on bone mineral density limits their use. Selective estrogen
      receptor modulators (SERMs) are nonsteroidal therapeutic agents that bind to the
      estrogen receptor and elicit tissue-specific estrogen agonist or antagonist
      effects. SERMs are effective in the treatment and prevention of breast cancer,
      and preclinical and clinical data suggest that these hormonal modulators may also
      be beneficial for the treatment of uterine leiomyomas. Continued efforts to
      understand the role of hormones in the development of this disease will allow the
      development of newer, less invasive treatment strategies, which will help
      minimize the negative impact of these tumors on women's health.

PMID- 15164306
TI  - Therapeutic potential for the selective progesterone receptor modulator
      asoprisnil in the treatment of leiomyomata.
AB  - Asoprisnil is a novel selective progesterone receptor modulator that exhibits
      partial agonist and antagonist activities in animals and humans. It demonstrates
      a high degree of progesterone receptor specificity and tissue selectivity.
      Although asoprisnil at high doses exhibited some antiglucocorticoid activity in
      animal models, no antiglucocorticoid effects were observed at therapeutic doses
      in humans. In male rats, asoprisnil showed mixed androgenic and antiandrogenic
      properties. Unlike antiprogestins, asoprisnil at high doses exhibited only
      marginal labor-inducing activity in guinea pigs during midpregnancy and was
      completely ineffective in inducing preterm parturition. In nonhuman primates,
      asoprisnil completely eliminated menstrual cyclicity and induced endometrial
      atrophy. Early clinical studies of asoprisnil in healthy volunteers demonstrated
      a dose-dependent suppression of menstruation, irrespective of the effects on
      ovulation, with no change in basal estrogen concentrations and no breakthrough
      bleeding. Phase 2 studies in subjects with uterine fibroids demonstrated that
      asoprisnil induced amenorrhea and reduced the volume of the dominant leiomyoma in
      a dose-dependent manner without altered basal estrogen and with virtually no
      clinical symptoms of estrogen deprivation. Asoprisnil seems to exhibit a direct
      inhibitory effect on both the endometrium and leiomyoma. In all studies to date,
      asoprisnil has maintained a favorable safety and tolerability profile. Thus,
      asoprisnil has the potential to target the major clinical symptoms of leiomyomata
      related to both menorrhagia and the size of the tumors and may, therefore, reduce
      or eliminate the need for surgery.

PMID- 15164307
TI  - Potential nonhormonal therapeutics for medical treatment of leiomyomas.
AB  - Uterine leiomyomas are a common disorder resulting in significant morbidity for
      women and substantial economic impact on the health care system. Current
      therapies include conservative surgery, hysterectomy, and hormonal therapy.
      Conservative surgical therapy often fails because of recurrence, and hysterectomy
      dramatically limits reproductive options. Radiologic therapies are associated
      with considerable risk of morbidity and mortality and are not likely to be
      compatible with reproduction. Hormonal therapies such as gonadotropin-releasing
      hormone (GnRH) analogues or progestins with or without estrogen are utilized by
      many patients, but long-term use of either is often responsible for unacceptable
      morbidity and hormonal therapies are not compatible with reproduction. Newer
      hormonal alternatives such as progesterone antagonists and selective agonists as
      well as "add-back" estrogen therapy in addition to GnRH analogues have been
      developed and show promise. However, no hormonal therapy that significantly
      alters estrogen and progesterone production or function is likely to be
      compatible with reproduction. Thus, it is important to develop novel nonhormonal
      therapies for medical treatment of leiomyomas. Other laboratories have evaluated
      pirfenidone, halofuginone, heparin, and interferon-alpha (IFN-alpha). Recent work
      in our laboratory suggests potential use of two additional classes of compounds,
      thiazolidinediones and tocopherol analogs. The rationale, evidence, and potential
      for the use of each of these compounds in the treatment of leiomyomas are
      discussed.

PMID- 15164308
TI  - Diagnostic imaging and vascular embolization for uterine leiomyomas.
AB  - This review article explains the relatively new therapy method of vascular
      embolization for leiomyomas of the uterus. The current concepts of diagnostic
      imaging of uterine leiomyomas with emphasis on preembolization imaging and
      postembolization follow-up are presented.

PMID- 15164309
TI  - Myomectomy and MRI-directed cryotherapy.
AB  - The purpose of this study was to identify alternatives to hysterectomy by
      transabdominal interventional magnetic resonance imaging-guided cryoablation.
      This represents a report of a prospective institutional review board-approved
      protocol to study interventional magnetic resonance imaging-guided cryoablation
      of uterine fibroid tumors. Women were selected on the basis of symptoms that were
      related to uterine fibroid tumors (bleeding, uterine pain, pelvic congestion,
      compression symptoms) and the absence of any desire for childbearing. Magnetic
      resonance imaging was performed before the procedure to measure the size and
      number of fibroid tumors, and follow-up magnetic resonance imaging determined the
      reduction of the lesion. Ten patients were originally included, and nine were
      treated and had substantial reduction in the uterine size (average, 65% volume
      reduction). The primary symptoms have either improved or resolved in eight of the
      nine women. This is the first reported review of interventional magnetic
      resonance imaging-directed cryotherapy of uterine fibroid tumors. This minimally
      invasive therapy produced shrinkage of the tumor in nine of our first ten
      patients.

PMID- 15164310
TI  - Endoscopic management of leiomyomata.
AB  - Prior to the advent of modern minimally invasive surgery techniques, the primary
      surgical management of symptomatic leiomyomata for women desiring future
      fertility or uterine conservation was through laparotomy. Today, many cases of
      intramural and subserous leiomyomata are managed with laparoscopic myomectomy and
      selected cases of submucosal leiomyomata are managed with hysteroscopic
      myomectomy. The management of leiomyomata endoscopically is one of the more
      challenging procedures in minimally invasive surgery and requires a skilled
      surgeon. Despite its benefits, such as faster postoperative recovery and
      potentially less postoperative adhesions compared with laparotomy, many concerns
      still exist. Although pregnancy rates for women with leiomyomata managed
      endoscopically are similar to those after laparotomy, a major worry continues to
      be the risk of uterine rupture. The risk is essentially unknown. Lastly, the risk
      of recurrence seems higher after laparoscopic myomectomy compared with
      laparotomy.

PMID- 15164311
TI  - On the significance of linkage studies of complex traits.

PMID- 15164314
TI  - Initiation of insulin therapy reduces serum concentrations of high-sensitivity C
      reactive protein in patients with type 2 diabetes.
AB  - Atherosclerosis has highly important chronic inflammatory aspects. We
      investigated anti-inflammatory effects upon initiating insulin therapy by
      measuring serum high-sensitivity C-reactive protein (hsCRP) and plasma fibrinogen
      and serum monocyte chemoattractant protein (MCP)-1in patients with poorly
      controlled type 2 diabetes. In 18 inpatients with type 2 diabetes, we measured
      serum hsCRP, plasma fibrinogen, serum MCP-1, body weight (BW), girth, and fasting
      plasma glucose (FPG) before and 2 weeks (14.0 +/- 2.5 days) after initiation of
      insulin therapy. Daily insulin doses (in units) were approximately 0.2 x BW (in
      kilograms). Various changes (ratio) were calculated as the ratio of the value
      during treatment to the pretreatment value. Significant decreases occurred for
      log(10) hsCRP and FPG (-0.025 +/- 0.557 mg/L, 215 +/- 64.3 mg/dL v -0.213 +/-
      0.571 mg/L, 129.8 +/- 32.1 mg/dL; P =.0121, and P =.00002, respectively). This
      was particularly true for log(10) hsCRP in patients whose BW was unchanged or
      increased between measurement (P =.0050). There were no significant differences
      between pretreatment and treatment values for fibrinogen and MCP-1. However, MCP
      1 decreased significantly in the group with high-value in the first time point
      (MCP-1 > 250 pg/mL, n = 9; P =.0224) compared with the low-value group (MCP-1 <
      250 pg/mL, n = 9; P =.3164). No significant correlation was found between hsCRP
      ratio and fibrinogen ratio, MCP-1 ratio, BW ratio, waist girth ratio, or FPG
      ratio. In conclusion, newly initiated insulin therapy in patients with poorly
      controlled type 2 diabetes decreased serum hsCRP. The decrease in hsCRP may have
      resulted largely from anti-inflammatory effects of insulin.

PMID- 15164313
TI  - Studies on the mechanism of caffeine action in alveolar macrophages: caffeine
      elevates cyclic adenosine monophosphate level and prostaglandin synthesis.
AB  - We have previously reported that the effects of caffeine on alveolar macrophages
      are dose-dependent; thus, at low concentrations caffeine prevents apoptosis and
      at moderate concentrations, the cells proceed into apoptosis. In the current
      study, the mechanism of caffeine action via prostaglandin synthesis and cyclic
      adenosine monophosphate (cAMP) was investigated using moderate concentrations of
      caffeine. The results show that the combination of caffeine with indomethacin, an
      inhibitor of prostaglandin synthesis, mediated caffeine's effect by increasing
      cellular viability and lowering superoxide anion production and DNA
      fragmentation. However, addition of exogenous prostaglandin E2 (PGE2) to the
      culture in the presence of caffeine had the opposite effect, in which the
      viability was decreased and anion superoxide production was increased. Incubation
      of macrophages with exogenous dibutyryl cAMP showed nearly similar effects to
      caffeine. At low concentrations (<50 micromol/L), higher viability and lower
      superoxide production pattern were evident and at higher concentrations (>50
      micromol/L) the cells proceeded into apoptosis. Therefore, it is suggested that
      caffeine exerts its effects on macrophages by altering cAMP level and
      prostaglandin synthesis.

PMID- 15164315
TI  - The relationships of vigorous exercise, alcohol, and adiposity to low and high
      high-density lipoprotein-cholesterol levels.
AB  - While vigorous exercise, alcohol, and weight loss are all known to increase high
      density lipoprotein-cholesterol (HDL-C), it is not known whether these
      interventions increase low HDL as effectively as has been demonstrated for normal
      HDL. This report tests the hypothesis that there may be differences in the
      calculated response of men and women with low versus high HDL-C to exercise,
      alcohol, and weight loss across the spectrum of HDL-C levels. Physican-supplied
      medical data from 7,288 men and 2,326 women were divided into deciles of self
      reported vigorous exercise, alcohol intake, body mass index (BMI), or body
      circumferences. Within each decile we determined the percentiles of the HDL
      distributions and average running distance, alcohol intake, BMI, or body
      circumference. Simple least-squares regression analysis was then used to estimate
      the slope for kth HDL percentile (k = 5%, 6%, ...,95%) versus running distance,
      alcohol intake, BMI, or body circumference across deciles. Bootstrap resampling
      was used to estimate standard errors and statistical significance for the
      regression lines. In both sexes, the increase in HDL-C per unit alcohol intake
      was at least twice as great at the 95th as at the 5th percentile of the HDL
      distribution. There was also a significant graded increase from the 5th to the
      95th HDL percentile for the slopes relating HDL to exercise (km run) and alcohol
      intake. Men's HDL-C declined in association with fatness (BMI, waist, and chest
      circumference) more sharply at the 95th than at the 5th percentile of the HDL
      distribution. The results of this study suggest that the effects of physical
      activity, alcohol, and weight reduction on HDL-C levels may be, to a large
      extent, dependent on the initial level with the greatest improvement achieved in
      subjects with high HDL and the least improvement in those having low HDL-C
      levels.

PMID- 15164316
TI  - Direct effects of high glucose and insulin on protein synthesis in cultured
      cardiac myocytes and DNA and collagen synthesis in cardiac fibroblasts.
AB  - The present study examined the direct effects of high glucose and insulin on
      protein synthesis in cardiac myocytes and DNA and collagen synthesis in cardiac
      fibroblasts. Cultured rat cardiac myocytes and fibroblasts were grown in media
      containing normal glucose, high glucose, or osmotic control, and incubated with
      or without insulin. In cardiac myocytes, high glucose had no effect, but insulin
      increased protein synthesis and atrial natriuretic peptide (ANP) secretion and
      gene expression. The extracellular signal-regulated protein kinase (ERK)/mitogen
      activated protein kinase (MAPK) inhibitor and the protein kinase C (PKC)
      inhibitor blocked insulin-induced protein synthesis. In cardiac fibroblasts, high
      glucose and osmotic control media increased DNA synthesis. Collagen synthesis and
      fibronectin and transforming growth factor-beta1 (TGF-beta1) mRNA expression were
      stimulated by high glucose, but not by osmotic control. Insulin increased DNA and
      collagen synthesis in fibroblasts, and the insulin-induced increase in DNA
      synthesis was blocked by the phosphatidylinositol 3 kinase (PI3K) inhibitor. Our
      findings suggest that cardiomyocyte protein synthesis is mainly regulated by
      insulin rather than high glucose and both high glucose and insulin contribute to
      fibroblast DNA and collagen synthesis. High glucose accelerates fibroblast DNA
      synthesis and collagen synthesis, and fibronectin and TGF-beta1 mRNA expression,
      dependent or independent of osmotic stress. Insulin regulates myocyte protein
      synthesis and fibroblast DNA synthesis through different intracellular
      mechanisms.

PMID- 15164317
TI  - Effects of hypoxia and hypoxic training on 8-hydroxydeoxyguanosine and
      glutathione levels in the liver.
AB  - The effects of hypoxia and hypoxic training on 8-hydroxydeoxyguanosine (8-OHdG),
      reduced glutathione (GSH), and oxidized glutathione (GSSG) levels and on
      glutathione reductase (GR) activity in the liver of rats were evaluated. Rats
      were divided into 3 groups: a hypoxia and exercise (HE) group, a hypoxia and
      sedentary (HS) group, and a normoxia and sedentary (NS) group. The liver 8-OHdG
      levels were lower in the HE and HS groups compared with the NS group (P <.05). No
      significant difference between in the liver 8-OHdG levels in the HE and HS groups
      were found. However, the liver GSH level in the HS group was lower than that in
      the NS group (P <.05), and the HE group had significantly higher levels of liver
      GSH than the HS group (P <.01). The activity of liver GR in the HS group was
      lower than that of the NS group (P <.05). Moreover, the liver GR activity of the
      HE group was significantly higher than that of the HS group (P <.01). No
      significant difference in liver GR activity between the HE and NS groups was
      noted. In conclusion, the present study confirmed that moderate hypoxia and
      hypoxic training attenuated liver DNA damage and decreased liver GSH levels and
      GR activity. These results indicate that moderate hypoxia and hypoxic training
      result in decreased oxidative stress.

PMID- 15164318
TI  - Central hypothalamic-pituitary-adrenal activity and the metabolic syndrome:
      Studies using the corticotrophin-releasing hormone test.
AB  - A number of studies have suggested that the metabolic syndrome (principally, the
      combination of hypertension, glucose intolerance, and dyslipidemia) is associated
      with subtle dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
      leading to raised circulating cortisol concentrations. The mechanisms underlying
      these observations are not known. We assessed the salivary cortisol response to
      awakening and pituitary-adrenal responses during a 100-microg human
      corticotrophin-releasing hormone (CRH) test and a dexamethasone-suppressed CRH
      test in a well-characterized group of 65-year-old men (n = 122). In the cohort
      from which this subgroup was drawn, there were associations between the
      components of the metabolic syndrome and 9 am cortisol concentration in line with
      previous studies. However, there were no significant associations between blood
      pressure, glucose tolerance, and lipid concentrations and the dynamic tests of
      HPA activity. We therefore found no evidence to suggest that exaggerated
      pituitary responsiveness or increased central drive to the pituitary, as
      determined by CRH testing, plays a part in the development of the metabolic
      syndrome.

PMID- 15164319
TI  - Regulation of metabolic rate and substrate utilization by zinc deficiency.
AB  - The trace metal zinc (Zn) is essential for the catalytic activity of many enzymes
      involved in energy nutrient metabolism and appears to regulate hormones, such as
      insulin, leptin, and thyroid hormone that play key roles in metabolism. Thus,
      this study used the continuous monitoring of oxygen consumption, carbon dioxide
      production, locomotion, and food intake to determine the effect of dietary Zn
      restriction on metabolic rate (MR), basal metabolic rate (BMR), and respiratory
      quotient (RQ). Rats were fed a Zn-adequate (ZA, 28 ppm) or Zn-deficient (ZD, <1
      ppm) diet for 8 days, followed by a 4-day refeeding period. To control for
      reductions in food intake that characteristically occur in ZD rats, an additional
      group was pair-fed (PF) the same amount ZA food eaten by ZD rats. The mean
      caloric intake of ZD rats was significantly lower than ZA rats by day 3. By day
      8, ZD and PF rats weighed 64% and 67% of ZA rats, respectively, (P <.01). Pair
      feeding resulted in increased locomotor activity, such that the distance traveled
      for PF rats (316 +/- 43 m) was 6 times that of ZA (53 +/- 6 m). Despite the fact
      that PF and ZD rats had the same food intake, there was no increase in locomotor
      activity in ZD rats suggesting that the mechanisms responsible for increased
      physical activity in food restricted animals may be Zn dependent. Furthermore,
      differences in activity between PF and ZD animals were not reflected in
      differences in MR. Both ZD and PF significantly reduced MR compared with ZA rats
      beginning on day 4. There was a significant relationship between RQ and caloric
      intake (r = 0.708, P <.01), but no specific effect of Zn status. Thus, while
      there may be an effect of Zn on locomotion and the energetic cost of activity, it
      appears that the most profound effect of Zn status on MR and substrate
      utilization is the result of Zn deficiency-induced anorexia.

PMID- 15164320
TI  - Fluvastatin improves endothelial dysfunction in overweight postmenopausal women
      through small dense low-density lipoprotein reduction.
AB  - Small dense low-density lipoprotein (sdLDL), which are often associated with
      obesity, are considered as the most atherogenic and have been shown to impair
      endothelial function. It is not known whether reduction of sdLDL by
      pharmacological intervention can improve endothelial function. Thirty-four
      consecutive postmenopausal women with >/=5.70 mmol/L total cholesterol were
      placed into either an overweight (body mass index [BMI] >/= 25.0, n = 22) or a
      normal-weight (BMI < 25.0, n = 12) group, and forearm blood flow (FBF) was
      measured using strain-gauge plethysmography during reactive hyperemia before and
      after fluvastatin treatment. At baseline, the peak FBF during reactive hyperemia
      in the overweight group was less than that in the normal-weight group (mean +/-
      SD, 13.6 +/- 4.4 v 22.2 +/- 4.0 mL/min/100 mL, P <.01). The maximal FBF after
      nitroglycerin was similar in both groups. In the stepwise multiple regression
      analysis, only the concentration of sdLDL was the predictor for peak FBF
      (standard coefficient = -0.517, P =.0115). The nonsignificant parameters for the
      correlations in the model were age, BMI, systolic blood pressure, the homeostasis
      model assessment of insulin resistance (HOMA-IR), hemoglobin A(1c) (HbA(1c)), and
      LDL-cholesterol. Fluvastatin treatment was associated with the recovery of the
      peak FBF in the overweight group but it did not influence that of the normal
      weight group. Changes in sdLDL fractions by fluvastatin correlated well with the
      peak FBF recovery. These results suggested that an increased sdLDL was linked to
      endothelial dysfunction in overweight postmenopausal women and fluvastatin
      treatment improved endothelial dysfunction by decreasing the atherogenic sdLDL
      fraction in this population.

PMID- 15164321
TI  - Long-term monitoring of insulin sensitivity in growth hormone-deficient adults on
      substitutive recombinant human growth hormone therapy.
AB  - Since the effects of recombinant human growth hormone (rhGH) replacement therapy
      on glucose metabolism are still a matter of debate, the aim of the present study
      was to evaluate the impact of long-term rhGH treatment on insulin sensitivity.
      Simple indices of insulin resistance (IR) and insulin sensitivity (IS), based on
      fasting glucose and insulin, such as the homeostasis model assessment of insulin
      resistance (HOMA-IR) and the quantitative insulin check index (QUICKI), were used
      to estimate the degree of IR and IS in 20 normoglycemic patients (11 men and 9
      women; mean age, 44 +/- 14 years) with severe adult-onset GH deficiency (GHD).
      Measurements were determined at baseline and after 1 and 5 years of continuous
      rhGH therapy. Basal values were compared to those obtained in 20 healthy sex- and
      age-matched controls. Starting rhGH dose ranged from 3 to 8 microg/kg/d in
      keeping with sex and age, then doses were titrated according to insulin-like
      growth factor-I (IGF-I) levels. At baseline all patients had low IGF-I levels (10
      +/- 5.4 nmol/L), high body mas index (BMI; 27.5 +/- 4 kg/m(2)), and elevated body
      fat percentage (BF%; 31.8 +/- 9.6). Fasting glucose and insulin levels, as well
      as HOMA-IR and QUICKI, did not differ significantly from those recorded in the
      control group. After 1 year of rhGH replacement therapy, normalization in IGF-I
      levels and a significant reduction in BF% were observed (P <.001), and these
      effects were maintained after 5 years of treatment. Fasting glucose increased
      from 79 +/- 10 to 87 +/- 13, and 87 +/- 12 mg/dL (P <.05) after 1 and 5 years of
      therapy, respectively. Fasting insulin significantly increased after 1 year,
      without further modifications in the long-term follow-up. HOMA-IR significantly
      increased from 2.1 +/- 1.7 to 2.5 +/- 1.7 (P <.05) after 1 year, then decreased
      to 2.3 +/- 1.5 (P = not significant [NS] v basal) after 5 years. A specular
      decrease in QUICKI from 0.37 +/- 0.05 to 0.34 +/- 0.03 (P <.01) occurred after 1
      year, with a trend to increase (0.35 +/- 0.04; P = NS v basal) after 5 years. No
      patient developed impaired fasting glucose. In conclusion, rhGH therapy
      determined an increase in fasting glucose and insulin levels, causing in the
      short-term period a worsening of IS. The sustained reduction in BF%, without
      further deterioration of IS, suggests that long-term beneficial effects on body
      composition may overcome the negative influence of GH on glucose metabolism.

PMID- 15164322
TI  - Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal
      women.
AB  - Statins are able to reduce cardiovascular morbility and mortality mainly through
      their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis,
      the identification of "ancillary" mechanisms has motivated studies evaluating the
      relationship between the use of statins and the modification of bone mineral
      density (BMD). To date, clinical trials have provided discordant results. The aim
      of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify
      BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared
      with a control group treated only with diet (n = 20) and matched by gender, age,
      body mass index (BMI), lipids, menopausal age, and BMD and the number of
      osteopenic, osteoporotic, and normal women (on the basis of T-score value).
      Exclusion criteria were secondary hyperlipemias and osteoporosis and current or
      previous therapy with statins, bisphosphonates, and estrogens. The BMD was
      measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA).
      In the group treated by simvastatin, BMD, both on the spine and femoral hip,
      showed a significant increase after 8 and 24 months, respectively (0.878 +/-
      0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101;
      and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8
      months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased
      1.6% after 8 months and 2.7% after 24 months. The group treated only with
      hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both
      on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and
      0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05).
      In conclusion, as partly suggested by retrospective or observational data, this
      longitudinal study indicates that simvastatin treatment exerts a beneficial
      effect on BMD.

PMID- 15164323
TI  - Effects of omega-3 fatty acid supplementation and exercise on low-density
      lipoprotein and high-density lipoprotein subfractions.
AB  - The purpose of this study was to examine the effect of combining exercise with
      omega-3 fatty acids (n-3fa) supplementation on lipoprotein subfractions and
      associated enzymes. Subjects were 10 recreationally active males, aged 25 +/- 1.5
      years (mean +/- SE), who supplemented n-3fa (60% eicosapentaenoic acid [EPA] and
      40% docosahexaenoic [DHA]) at 4 g/d for 4 weeks. Before and after
      supplementation, subjects completed a 60-minute session of treadmill exercise at
      60% Vo(2)max. Following a 24-hour diet and activity control period, blood was
      collected immediately before and after the exercise session to assess lipid
      variables: high-density lipoprotein cholesterol (HDL-C) and subfractions, low
      density lipoprotein cholesterol (LDL-C) and subfractions and particle size,
      lecithin:cholesterol acyltransferase (LCAT) activity, and cholesterol ester
      transfer protein (CETP) activity. Supplementation with n-3fa alone increased
      total HDL-C and HDL(2)-C, while exercise alone increased total HDL-C, HDL(3)-C,
      and total LDL-C. LDL subfractions, particle size, and LCAT and CETP activities
      were not affected by supplementation. Combination treatment resulted in an
      additive effect for HDL(3)-C only and also increased LDL(1)-C versus baseline.
      LCAT and CETP activities were not affected by treatments. These results suggest
      that n-3fa supplementation or an exercise session each affect total HDL-C and
      subfractions but not LDL-C or subfractions. In addition, the combination of n-3fa
      and exercise may have additional effects on total HDL-C and LDL-C subfractions as
      compared to either treatment alone in active young men.

PMID- 15164324
TI  - Susceptibility of low-density lipoprotein to oxidation and circulating cell
      adhesion molecules in young healthy adult offspring of parents with type 2
      diabetes.
AB  - Relatives of subjects with type 2 diabetes carry an increased risk for diabetes
      and cardiovascular disease. Oxidative modification of low-density lipoprotein
      (LDL) and proinflammatory processes are believed to have central roles in
      atherogenesis. We have investigated the susceptibility of LDL to oxidation and
      circulating cell adhesion molecules in healthy, glucose-tolerant adults (aged 18
      to 38 years) with (12 men, 2 women) and without (controls; 12 men, 2 women) a
      parental history of type 2 diabetes. From fasting blood samples, oxidation of LDL
      was initiated with copper ions and adhesion molecules were measured using
      immunoassays. Groups were similar with respect to age, body mass index (BMI),
      blood pressure, plasma glucose, and serum lipids. Resistance of LDL to oxidation
      was reduced in offspring of parents with type 2 diabetes (time to Vmax, 80.1 +/-
      2.2 v 91.4 +/- 2.6 minutes, P =.003). Plasma hydroperoxides did not differ
      between groups (1.2 +/- 0.1 v 1.1 +/- 0.1 micromol/L). Soluble intracellular
      adhesion molecule-1 (sICAM1) was elevated in offspring compared with controls
      (571 +/- 20 v 447 +/- 20 microg/L, P =.0002). Soluble vascular cell adhesion
      molecule-1 (sVCAM-1) (1,184 +/- 76 v 1084 +/- 56 microg/L, P =.31) and E-selectin
      (53 +/- 8 v 53 +/- 7 microg/L, P =.98) did not differ between groups. Reduced
      resistance of LDL to oxidation and increased circulating sICAM-1 in young healthy
      adult offspring of parents with type 2 diabetes may be intrinsic to increased
      risk of atherosclerosis in these subjects.

PMID- 15164325
TI  - Moderately elevated plasma homocysteine impairs functional endothelial recovery
      following denudation of mouse carotid arteries.
AB  - Increased total plasma homocysteine is an independent risk factor for
      cardiovascular disease. This study was designed to determine whether it can
      impair endothelial function, by examining the recovery of acetylcholine-evoked
      relaxation following mechanical denudation of the endothelium in the arteries of
      cystathionine beta-synthase knockout (CbetaS(+/-)) mice. Heterozygous CbetaS(+/-)
      mice had total plasma homocysteine concentrations significantly higher (8.9 +/-
      1.1 micromol/L, n = 12) than strain-matched wild-types (4.6 +/- 0.4 micromol/L, n
      = 5; P =.003). Left common carotid arteries were denuded of endothelium using a
      250-microm polytetrafluoroethylene filament. After 10 days, when the endothelium
      had completely regrown, relaxation to acetylcholine was measured in precontracted
      segments of artery. Uninjured right carotid arteries from the same animals served
      as internal controls. Relaxation to acetylcholine was significantly attenuated in
      the injured arteries of the CbetaS(+/-) mice, compared to wild-types (P =.017);
      furthermore, there was a significant negative correlation between sensitivity to
      acetylcholine and total plasma homocysteine concentration measured in the same
      animal (r = -0.69, P <.003). These data suggest that even modest homocysteinemia
      has a deleterious effect on the function of healed endothelium in mouse arteries.
      This may account for its adverse influence on chronic cardiovascular disease.

PMID- 15164326
TI  - Effect of glucosamine on apolipoprotein AI mRNA stabilization and expression in
      HepG2 cells.
AB  - Previously published studies suggest that an alteration in hexosamine flux
      induces a state of insulin resistance in muscle, liver, and other cell types.
      Glucosamine also alters the expression of several genes through an effect on
      transcription factors such as Sp1. Since the anti-atherogenic protein
      apolipoprotein AI (apoAI) is positively regulated by insulin, at least partly
      through its effect on Sp1, we investigated the effect of glucosamine on apoAI
      gene expression in the hepatocyte cell line, HepG2. By 24 hours of treatment with
      0.1, 1, or 3 mmol/L glucosamine, the amount of apoAI protein secreted into the
      culture media increased 1.8-fold, 5.5-fold, and 2.3-fold, respectively. The
      decline in apoAI secretion at the highest glucosamine levels may be due to
      toxicity since the percentage of cells able to exclude trypan blue was lower in
      this group than in control cells (98.5% +/- 1.5% in control cells v 89.2% +/-
      2.1% in cells treated with 3 mmol/L glucosamine, P <.01). ApoAI mRNA levels
      increased 2.4-fold in hepatocytes treated with 1 mmol/L glucosamine for 24 hours
      (1,158.1 +/- 78.8 v 482.2 +/- 24.3 arbitrary integrator units [AIU], P <.02),
      suggesting that the increase in apoAI protein secretion was due, at least partly,
      to an increase in apoAI mRNA levels. However, glucosamine had no effect on apoAI
      gene transcription rate as measured by nuclear runoff analysis (3,155 +/- 46.0 in
      control cells v 3,181 +/- 30.0 AIU in glucosamine-treated cells). Similarly,
      apoAI promoter activity measured in HepG2 cell transfected with an apoAI reporter
      plasmid containing the full-length apoAI promoter including an insulin-responsive
      Sp1 binding site did not change with glucosamine addition. In this assay, the
      chloramphenicol acetyltransferase (CAT) activity was 12.4% +/- 3.1%, 10.1% +/-
      2.4%, 9.8% +/- 2.0%, 9.7% +/- 2.2%, and 11.9% +/- 2.9% in cells treated with 0,
      0.03, 0.1, 0.3, and 1 mmol/L glucosamine, respectively. The apoAI mRNA turnover
      studies showed that 1 mmol/L glucosamine treatment of HepG2 cells was associated
      with increased apoAI mRNA half-life, from 7.6 to 16.6 hours. These findings
      suggest that increases in apoAI gene expression by glucosamine occur primarily
      through stabilizing apoAI mRNA.

PMID- 15164327
TI  - Effect of sauna bathing and beer ingestion on plasma concentrations of purine
      bases.
AB  - To determine whether sauna bathing alone or in combination with beer ingestion
      increases the plasma concentration of uric acid, 5 healthy subjects were tested.
      Urine and plasma measurements were performed before and after each took a sauna
      bath, ingested beer, and ingested beer just after taking a sauna bath, with a 2
      week interval between each activity. Sauna bathing alone increased the plasma
      concentrations of uric acid and oxypurines (hypoxanthine and xanthine), and
      decreased the urinary and fractional excretion of uric acid, while beer ingestion
      alone increased the plasma concentrations and urinary excretion of uric acid and
      oxypurines. A combination of both increased the plasma concentration of uric acid
      and oxypurines, and decreased the urinary and fractional excretion of uric acid,
      with an increase in the urinary excretion of oxypurines. The increase in plasma
      concentration of uric acid with the combination protocol was not synergistic as
      compared to the sum of the increases by each alone. Body weight, urine volume,
      and the urinary excretion of sodium and chloride via dehydration were decreased
      following sauna bathing alone. These results suggest that sauna bathing had a
      relationship with enhanced purine degradation and a decrease in the urinary
      excretion of uric acid, leading to an increase in the plasma concentration of
      uric acid. Further, we concluded that extracellular volume loss may affect the
      common renal transport pathway of uric acid and xanthine. Therefore, it is
      recommended that patients with gout refrain from drinking alcoholic beverages,
      including beer, after taking a sauna bath, since the increase in plasma
      concentration of uric acid following the combination of sauna bathing and beer
      ingestion was additive.

PMID- 15164328
TI  - Candesartan, an angiotensin II receptor blocker, improves left ventricular
      hypertrophy and insulin resistance.
AB  - A growing body of evidence indicates that the renin-angiotensin system and
      insulin resistance play crucial roles in left ventricular hypertrophy (LVH) in
      patients with essential hypertension (EH). Angiotensin II receptor blockers (ARB)
      have been reported to regress LVH and improve insulin resistance. We tested the
      hypothesis that candesartan, an ARB, could regress LVH, in association with
      improvement of insulin resistance in EH patients. The study participants were
      nondiabetic and never-treated EH patients (n = 10). Candesartan was administered
      at a mean final dose of 10.4 +/- 2.1 mg/d for 24 weeks. Candesartan treatment
      resulted in a significant decrease of systolic and diastolic blood pressures, LV
      mass index (LVMI), homeostasis model assessment (HOMA) index, and plasma brain
      natriuretic peptide (BNP). A significant correlation was observed between the
      percent decrease in LVMI and that of both the HOMA index (r = 0.83, P <.001) and
      BNP (r = 0.71, P <.005). Stepwise regression analyses revealed that the percent
      decrease of HOMA index was an independent predictor for both percent decrease in
      LVMI and plasma BNP. Our findings suggest that pharmacological blockade of
      angiotensin II receptors by candesartan could improve LVH in never-treated EH
      patients, which may relate to the improvement of insulin resistance.

PMID- 15164329
TI  - Augmenting leptin circadian rhythm following a weight reduction in diet-induced
      obese rats: short- and long-term effects.
AB  - The current study sought to examine whether leptin injections following a weight
      reduction in diet-induced obese rats would reduce both the enhanced food intake
      and body weight (BW) regain observed during the refeeding phase. Female Wistar
      rats (n = 100, 20 per group) were divided into 5 groups: (1) LEP rats were fed a
      high-fat (HF) diet (35% wt/wt) for 8 weeks to induce obesity and were then food
      restricted (50% ad libitum) with a fortified high-fat diet for 2 weeks to induce
      a 20% BW loss. These rats were then refed the HF diet ad libtum for another 11
      weeks. They were given leptin injections (200 microg/kg BW, twice daily,
      intraperitoneally ) for 19 days concomitant with the onset of refeeding. (2) SAL
      rats were treated in the same manner as LEP rats except that they were given
      saline injections; (3) PF rats were treated like SAL rats except that they were
      pair-fed with the LEP rats; (4) HFC rats were fed HF diet ad libitum; and (5) LFC
      rats were fed a low-fat (LF) diet (AIN-93M) ad libitum. Ten rats from each group
      were killed after leptin treatment and at the end of the study. Food and caloric
      intakes were monitored, and body composition and plasma glucose, insulin, and
      leptin levels were assessed at death. Leptin injections after a weight reduction
      briefly reduced energy intake during the first week only. After 19 days of
      treatment and to the end of the study, LEP and SAL rats were similar in energy
      intake, BW (LEP: 393 +/- 11.2 g, SAL: 371 +/- 14.1; difference not significant
      [NS]) and total body fat percent (LEP: 19.3 +/- 1.5, SAL: 17.6 +/- 1.5; NS).
      Leptin treatment induced hyperinsulinemia and insulin resistance. All of the
      metabolic abnormalities observed at the end of treatment period disappeared at
      the end of the study (8 weeks post-leptin injection). We conclude that bolus
      leptin injections to manipulate leptin circadian rhythm in diet-induced obese
      rats after a weight reduction caused temporary insulin resistance and
      hyperinsulinemia, and were ineffective in influencing food intake, BW, and fat
      content. Leptin resistance was evident following 1 week of treatment in this
      study. Leptin treatment had no effect on body fat content both short-term and
      long-term. Exogenous leptin treatment may, in the long run, increase leptin
      resistance in diet-induced obese animals. Hence, long-term leptin treatment may
      not be beneficial to obese individuals consuming a HF diet.

PMID- 15164330
TI  - Acute regulation of adiponectin by free fatty acids.
AB  - Little is known about the acute regulation of adiponectin in humans. In animal
      studies, adiponectin increases the clearance of free fatty acids (FFA) from the
      circulation by increasing skeletal uptake and oxidation of lipid, thereby
      regulating the FFA concentration. However, it is unknown if FFA regulate
      adiponectin. The aim of the present study was to investigate the effect of an
      acute reduction in free fatty acids on adiponectin concentration in healthy
      subjects. Ten normal male subjects were admitted for 2 inpatient visits and
      randomized to receive either acipimox (500 mg orally at 2 am and again at 6 am)
      or placebo on the first visit and vice versa on the second visit. Adiponectin,
      FFA, insulin and glucose were measured at 7:45 am. FFA concentrations were
      significantly lower after acipimox than placebo administration (0.08 +/- 0.02
      mEq/L v 0.35 +/- 0.53 mEq/L, P <.05). Adiponectin concentrations were also
      significantly lower after acipimox than placebo administration (7.4 +/- 1.2
      microg/mL v 10.3 +/- 1.7 microg/mL, P <.05). The change in FFA between acipimox
      and placebo correlated significantly with the change in adiponectin (r = 0.66, P
      <.05), eg, the larger the reduction in FFA in response to acipimox, the larger
      the reduction in adiponectin. These results suggest that acute lowering of FFA is
      associated with decreased adiponectin concentrations.

PMID- 15164331
TI  - Evidence for increased and insulin-resistant lipolysis in skeletal muscle of high
      fat-fed rats.
AB  - The metabolic and isotopic profiles of glycerol in skeletal muscle were examined
      using awake, fasted lean and high-fat-induced obese rats, and hyperinsulinemic
      euglycemic clamp was performed to assess the effect of insulin. During the clamp,
      Intralipid (no heparin; Fresnius Kabi Clayton, Clayton, NC), free fatty acids,
      glycerol, and glucose were coinfused to maintain their respective basal plasma
      levels in both groups. At steady-state, [U-(14)C]glycerol was infused
      intravenously for 120 minutes followed by muscle biopsy. The classical phenotypic
      characteristics of obesity, namely, reduced insulin-stimulated glucose uptake, a
      failure to suppress systemic lipolysis by insulin, and elevated plasma fatty acid
      concentration, were observed in the obese rats. Novel observations showed that in
      the basal state, the isotopic specific activity (S.A.) of glycerol (dpm/nmol) in
      gastrocnemius (0.03 v 0.12), soleus (0.05 v 0.12), and tibialis anterior (0.03 v
      0.12) was significantly lower (all P <.003) in obese than in lean rats despite
      similar concentrations, indicating an active basal intramyocellular lipolysis. In
      addition, the lipolysis appeared resistant to insulin because the suppression of
      muscle glycerol during the clamp was 8%, 12%, and 8% in obese compared to 67%,
      71%, and 63% in the lean control for gastrocnemius (P =.001), soleus (P =.007),
      and tibialis anterior (P =.004), respectively. The active intracellular lipolysis
      likely disturbs metabolic functions that may contribute to insulin resistance.

PMID- 15164332
TI  - Contributions of dysregulated energy metabolism to type 2 diabetes development in
      NZO/H1Lt mice with polygenic obesity.
AB  - New Zealand Obese (NZO) male mice develop a polygenic juvenile-onset obesity and
      maturity-onset hyperinsulinemia and hyperglycemia (diabesity). Here we report on
      metabolic and molecular changes associated with the antidiabesity action of
      CL316,243 (CL), a beta(3)-adrenergic receptor agonist. Dietary CL treatment
      initiated at weaning reduced the peripubertal rise in body weight and adiposity
      while promoting growth without suppressing hyperphagia. The changes in adiposity,
      in turn, suppressed development of hyperinsulinemia, hyperleptinemia,
      hyperlipidemia, and hyperglycemia. These CL-induced alterations were reflected by
      decreased adipose tissue mass, increased expression of transcripts for uncoupling
      protein-1 (UCP-1), peroxisome proliferator-activated receptor alpha (PPARalpha),
      peroxisome proliferater-activated receptor coactivator-1 (PGC-1), and robust
      development of brown adipocyte function in white fat. Increased drug-mediated
      energy dissipation elicited a 1.5 degrees C increase in whole body temperature
      under conditions of increased food intake but with no change in physical
      activity. Indirect calorimetry of mice treated with CL showed both increased
      energy expenditure and a restoration of a prominent diurnal pattern in the
      respiratory exchange ratio suggesting improved nutrient sensing. Our data suggest
      that CL promotes increased energy dissipation in white and brown fat depots by
      augmenting thermogenesis and by metabolic re-partitioning of energy in a
      diabesity-protective fashion. This is the first report demonstrating the effects
      of dietary beta(3)-agonist in preventing the onset of diabesity in a polygenic
      rodent model of type 2 diabetes.

PMID- 15164333
TI  - Propionic acidemia: unusual course with late onset and fatal outcome.
AB  - A 4 1/2-year-old girl with a so far unremarkable medical history became comatose
      during a simple infection. She showed severe metabolic acidosis without elevation
      of lactate. In blood the branched-chain amino acids were increased. In urine
      ketone-bodies, increased 3-OH-isovaleric and 3-OH propionic acid excretion were
      detected, while methylmalonate was not found. The profile of acylcarnitines
      revealed increased propionylcarnitine. Despite restriction of protein supply,
      high-caloric nutrition, correction of acidosis, and supplementation of biotin and
      carnitine, the girl died 2 days after admission due to arrhythmia of the heart.
      In skin fibroblasts the activity of propionyl-coenzyme A carboxylase (PCC) was
      markedly decreased. Mutation analysis confirmed the diagnosis of propionic
      acidemia (PA) with compound heterozygosity for 2 new missense mutations
      L417W/Q293E in the PCCA gene, with the mother carrying the Q293E and the father
      the L417W mutation. Late-onset PA should be included in the differential
      diagnosis of unclear coma. Determination of the acylcarnitines using tandem mass
      spectrometry as well as organic acids in urine is recommended.

PMID- 15164334
TI  - Effect of chenodeoxycholic acid on 11beta-hydroxysteroid dehydrogenase in various
      target tissues.
AB  - Glucocorticoids are metabolized by isoforms of the enzyme 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD). There is some controversy concerning the bile acid,
      chenodeoxycholic acid (CDCA), as a potential endogenously produced inhibitor of
      11beta-HSD. The present experiments were designed to determine the relative
      specificity of CDCA for both isoforms of 11beta-HSD and to assess the biological
      relevance of inhibition in vascular tissue. IC(50) values (concentrations which
      inhibit 50% of the enzyme reaction) were calculated using rat liver microsomes as
      a source of 11beta-HSD1 dehydrogenase, Leydig cells for 11beta-HSD1 dehydrogenase
      and reductase, aorta for 11beta-HSD1 dehydrogenase and reductase, and sheep
      kidney for 11beta-HSD2 dehydrogenase. In each case, CDCA functioned as a potent
      inhibitor of 11beta-HSD1 dehydrogenase with IC(50) values of ranging from 0.2 to
      7 micromol/L in contrast to 37 to 200 micromol/L for 11beta-HSD1 reductase. CDCA
      exhibited relatively weak inhibitory activity against 11beta-HSD2 from sheep
      kidney with an IC(50) of 70 micromol/L. The effect of CDCA on vascular
      contraction was studied in aortic rings isolated from Spague-Dawley rats
      incubated in medium containing corticosterone 10 nmol/L +/- CDCA (1 micromol/L)
      for 24 hours. Rings were stimulated with graded concentrations of phenylephrine
      (PE) (10 nmol/L, 100 nmol/L, and 1 micromol/L). Rings exposed to corticosterone
      and CDCA consistently demonstrated a greater contractile response at lower doses
      of PE (63% at PE 10 nmol/L, P <.001; 20% at PE 100 nmol/L, P <.025; and 10% at PE
      1 micromol/L, not significant [NS]) compared to control preparations incubated
      with cortiosterone alone. These studies demonstrate (1) that CDCA preferentially
      affects 11beta-HSD1 dehydrogenase; (2) CDCA does inhibit 11beta-HSD2
      dehydrogenase and 11beta-HSD1 reductase but only at high(er) concentrations
      exceeding 70 micromol/L and 37 micromol/L, respectively; and (3) inhibition of
      11beta-HSD1 dehydrogenase in aortic rings by CDCA (1 micromol/L) enhances the
      contractile response of corticosterone plus PE.

PMID- 15164335
TI  - Cholesterol absorption and hepatic acyl-coenzyme A:cholesterol acyltransferase
      activity play major roles in lipemic response to dietary cholesterol and fat in
      laboratory opossums.
AB  - Partially inbred lines of laboratory opossums differ considerably in their low
      density lipoprotein (LDL) cholesterol responses to dietary cholesterol and fat.
      Genetic analysis suggested that a single major gene is responsible for the
      variation in LDL cholesterol on the high cholesterol and high fat (HCHF) diet. We
      measured cholesterol absorption and acyl-coenzyme A:cholesterol acyltransferase
      (ACAT) activity in intestine and liver to narrow the search for the major gene.
      We measured plasma lipoproteins and percent cholesterol absorption by the fecal
      isotope ratio method in high and low responding lines of opossums on basal and
      HCHF diets. We also measured lipids in liver and ACAT activity in liver and
      intestine on the HCHF diet. High and low lines exhibited no differences in
      percent cholesterol absorption on the basal diet. However, high responding
      opossums had significantly higher percent cholesterol absorption, hepatic free
      and esterified cholesterol, and hepatic ACAT activity than low responding
      opossums on the HCHF diet. Hepatic ACAT activity but not the intestinal ACAT
      activity was associated with hepatic cholesterol concentration and percent
      cholesterol absorption. Cholesterol absorption is a major determinant of diet
      induced hyperlipidemia in opossums. Hepatic ACAT activity but not the intestinal
      ACAT may also play a role in diet-induced hyperlipidemia in opossums.

PMID- 15164336
TI  - High intake of cholesterol results in less atherogenic low-density lipoprotein
      particles in men and women independent of response classification.
AB  - The influence of a high-cholesterol diet on the atherogenicity of the low-density
      lipoprotein (LDL) particle was examined by measuring LDL peak diameter and
      composition, LDL susceptibility to oxidation, and the distribution of cholesterol
      between LDL subclasses. The crossover intervention randomly assigned 27
      premenopausal women and 25 men (18 to 50 years) to an egg (640 mg/d additional
      dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) diet for
      30 days, followed by a 3-week washout period. Subjects were classified as either
      hyperresponders (>2.5 mg/dL increase in plasma cholesterol for each 100 mg
      additional dietary cholesterol consumed) or hyporesponders to dietary
      cholesterol. Sex was found to have a significant effect on 3 of the parameters
      examined. LDL peak diameter was significantly larger (P <.005) in females (26.78
      +/- 0.59 nm, n = 27) as compared with males (26.52 +/- 0.49 nm, n = 25),
      regardless of response to dietary cholesterol. The LDL particles of the male
      participants also had a higher number of triglyceride (TG) and cholesteryl ester
      (CE) molecules (P <.01); however, cholesterol ester transfer protein (CETP)
      activity was higher in females (P <.05). Response classification also revealed
      significant differences in the determination of LDL subclasses. Independent of
      sex, the LDL-1 particle (P <.05), which is considered to be less atherogenic, was
      predominant in hyperresponders and this finding was associated with increased
      cholesterol intake (interactive effect, P <.001). In addition, CETP and lecithin:
      cholesterol acyltransferase (LCAT) activities were higher in hyperresponders
      during the egg period (interactive effect, P <.05). Sex, response to cholesterol
      intake, and diet were not found to affect the susceptibility of LDL to oxidation
      (P > 0.5). Because LDL peak diameter was not decreased and the larger LDL-1
      subclass was greater in hyperresponders following egg intake, these data indicate
      that the consumption of a high-cholesterol diet does not negatively influence the
      atherogenicity of the LDL particle.

PMID- 15164337
TI  - Ultrastructure of the osteocyte process and its pericellular matrix.
AB  - Osteocytes are believed to be the mechanical sensor cells in bone. One potential
      physical mechanism for the mechanosensing process is that osteocytes directly
      sense the deformation of the substrate to which they are attached. However, there
      is a fundamental paradox in this theory: tissue-level strains in whole bone are
      typically <0.2%, yet an extensive range of in vitro experiments show that dynamic
      substrate strains must be at least an order of magnitude larger in order for
      intracellular biochemical responses to occur. Recently, a theoretical model was
      developed (You et al. J. Biomech., 2001; 34:1375-1386) that provides a possible
      mechanism by which mechanical loading-induced fluid flow in the lacuno
      canalicular system, under routine physical activity, can produce cellular-level
      strains on the osteocyte processes that are at least one order of magnitude
      larger than bone tissue deformations. This would resolve the fundamental paradox
      mentioned above. In this work we experimentally confirm and quantify the
      essential ultrastructural elements in this model: 1) the presence of the
      transverse elements that bridge the pericellular space surrounding the osteocyte
      process, which interact with the fluid flow and lead to an outward hoop tension
      on the process; and 2) the presence of bundled F-actin in the osteocyte
      processes, which resists the outward hoop tension and limits the cell process
      membrane deformation. Morphological data to support these assumptions are scant.
      Special staining techniques employing ruthenium III hexamine trichloride (RHT)
      were developed to elucidate these structures in the humeri of adult mice.

PMID- 15164338
TI  - Development of the trabecular structure within the ulnar medial coronoid process
      of young dogs.
AB  - This study describes the timing of development of the trabecular structure of the
      ulnar medial coronoid process (MCP) in the dog. The right MCPs of nine healthy
      golden retrievers, aged 4 to 24 weeks, without signs of secondary joint disease
      were dissected and scanned with microcomputed tomography (micro-CT) at a voxel
      size of 34 microm to determine histomorphometric parameters. Bone volume fraction
      and mean trabecular separation show a reciprocal pattern in time, reflecting an
      initial high bone density (and low trabecular separation), and then a sharp drop
      in density at 8-10 weeks, followed by a gradual increase to high values at 24
      weeks. With a similar bone volume fraction as in young bone, the older bone shows
      thicker trabeculae and a more plate-like structure. This is reflected in the much
      smaller number of trabeculae and the lower surface/volume ratio at higher age. An
      anisotropic structure of the trabeculae with an orientation in the direction of
      the proximodistal axis of the ulna is already present at 6 weeks after birth.
      This primary alignment was perpendicular to the humeroulnar articular surface,
      matching the direction of the compressive forces applied to the MCP by the
      humeral trochlea. The secondary alignment appeared at 13 weeks after birth and
      was directed along the craniocaudal axis of the MCP, toward the attachment of the
      anular ligament. In comparison with data from long bones and vertebrae, the
      findings of a high bone volume fraction and a well-defined trabecular alignment
      at a very early age are remarkable. The high bone volume fraction is possibly a
      remnant of the fetal trabecular structure, as dogs are relatively immature at
      birth compared to other animals. Soon after the start of steady locomotion, the
      trabecular structure changes into a more mature-like structure. The early
      trabecular alignment is possibly a reflection of the early load-bearing function
      of the MCP in the elbow joint.

PMID- 15164339
TI  - Ontogeny of the VATER kidney in a rat model.
AB  - By exposing rat fetuses to adriamycin prenatally, a rat model of VATER
      association has been created. Absence of the fetal bladder is prominent and the
      kidneys show features of chronic obstruction with hydronephrosis/hydroureter,
      loss of parenchyma, fewer glomeruli, and less differentiation. The aim of this
      study was to elucidate this rat model, to determine exactly when the changes in
      the kidneys develop, hopefully thereby to expand our understanding of congenital
      obstructive uropathy. Timed-pregnant Sprague-Dawley rats were injected
      intraperitoneally with adriamycin on days 6-9 of gestation. The control group
      received saline. Fetuses were recovered on gestational days (GDs) 20, 19, 18, 17,
      16, 15, 14, 12, and 10 (total, 120 control, 121 treated). Macroscopic features
      were determined. Serial sections were then taken and stained with hematoxylin and
      eosin. Comparisons were made under light microscopy. The metanephric kidney first
      became apparent at GD12. The development of the control and treated kidneys
      appeared similar till GD18. Beyond this day, the treated kidneys exhibited
      increasing degrees of distension of Bowman's capsule, ducts, and subsequently
      pelvis and ureter. There were fewer levels of glomeruli, which were also less
      differentiated. Less differentiation was also noted in the medulla, and with time
      this became thin in comparison to the control kidneys. By GD20, the renal pelvis
      was grossly dilated with a blunted papilla, and the renal parenchyma was thin.
      Prenatal exposure of rat fetuses to adriamycin results in kidneys that are
      chronically obstructed, as the majority of the fetuses show absence of the
      bladder. Absence of renal dysmorphology until GD18, when urine is first produced,
      suggests strongly that the effect of adriamycin on the kidney is indirect, via
      agenesis of the bladder and secondary to backpressure from early urine
      production. This is a unique, simple, and reliable model of fetal obstructive
      uropathy and will be very useful to facilitate further investigation into its
      pathophysiology and to explore new treatment options.

PMID- 15164340
TI  - Calbindin-immunoreactive neurones in the ovine rumen.
AB  - In small laboratory animals, such as guinea pigs, immunoreactivity for the
      calcium-binding protein calbindin (CALB) can be used to distinguish functionally
      different classes of myenteric neurones. The rumen of sheep is a highly
      specialized gastrointestinal region, and the control of its functions requires
      specific intrinsic innervation patterns. The aim of this study was to
      neurochemically identify and characterize CALB-positive myenteric neurones of the
      ovine rumen. Therefore, we performed quadruple immunohistochemistry against CALB,
      substance P (SP), vasoactive intestinal peptide (VIP), and nitric oxide synthase
      (NOS) using whole-mount preparations of the ruminal myenteric plexus. On average,
      3 +/- 2 and 1 +/- 0.4 myenteric neurones/ganglion were CALB-immunoreactive in
      suckling lambs and adult sheep, respectively. These neurones had Dogiel type-I
      morphology. Most of them (89.2% +/- 8.7% and 71.7% +/-44.8% in suckling lambs and
      adult sheep, respectively) did not colocalize any of the other antigenes. Since
      it has been shown in previous studies that ruminal myenteric neurones are
      immunoreactive for either choline acetyltransferase (ChAT) or NOS, we defined
      neurones which were CALB-positive and NOS-negative as CALB/ChAT. The other CALB
      positive neurones were encoded CALB/NOS/+/-VIP (10.3% +/- 9.3% and 26.7% +/-
      46.2% in suckling lambs and adult sheep, respectively) or CALB/ChAT/SP (0.5% +/-
      1.0% and 1.7% +/- 1.9% in suckling lambs and adult sheep, respectively). We used
      cryostat sections of the ruminal wall to analyze the projections of the CALB
      positive neurones. CALB-immunoreactive somata were exclusively located within the
      myenteric plexus. CALB-immunoreactive nerve fibers were found primarily in the
      lamina propria of the ruminal papillae. We conclude that CALB-positive myenteric
      neurones within the ovine rumen project to the epithelium; however, their
      functional role remains to be investigated.

PMID- 15164341
TI  - Reversible formation of giant and normal-sized mitochondria in gastric parietal
      cells of guinea pigs.
AB  - Mitochondria occasionally increase in size in response to metabolic injury.
      Numerous studies have reported giant mitochondria in patients with various
      diseases and animals with metabolic injuries, and there are few reports on giant
      mitochondria in normal cells under physiological conditions. Here, we report a
      reversible formation of giant and normal-sized mitochondria in gastric parietal
      cells of guinea pigs. We morphometrically analyzed the frequency distribution of
      mitochondrial area on ultrathin sections of parietal cells in guinea pigs fed
      freely (control group), starved for 60-72 hr (starvation group), and starved and
      then injected with histamine (histamine group). The distribution was
      significantly different between the control and starvation group and between the
      starvation and histamine group: the histogram of the starvation group
      significantly shifted toward large mitochondria compared with that of the control
      or histamine group; the frequency of mitochondria more than 2 microm2 in size was
      significantly higher in the starvation group than that in the control or
      histamine group. This is the first report that clearly demonstrated the presence
      of giant mitochondria in gastric parietal cells under the starved condition and a
      mitochondrial recovery in a normal size after the administration of histamine.
      Because gastric parietal cells change their membrane system according to the
      state of gastric acid secretion, the present data may offer new insight into the
      morphological changes in gastric parietal cells.

PMID- 15164342
TI  - Histochemical similarities of mucins produced by Brunner's glands and pyloric
      glands: A comparative study.
AB  - Mucins of the gastroduodenal junction are secreted by the mucous surface and
      mucus-producing glandular cells in the stomach, and by goblet cells and Brunner's
      glands in the duodenum. Developmental studies have demonstrated that Brunner's
      glands can arise from undifferentiated gastric epithelium and/or intestinal
      epithelium in the proximal duodenum. The aim of this study was to investigate the
      carbohydrate composition of mucins from this region and compare it with that of
      mucins from Brunner's glands to evaluate the probable evolution of mucins from
      these glands. Toward that end, paraffin sections from 13 mammalian species were
      stained by classic carbohydrate histochemistry and treated with 13 lectins. In
      general, the mucous surface cells of the stomach, pyloric glands, duodenal goblet
      cells, and Brunner's glands secretory epithelium had different lectin-binding
      patterns. However, the lectin-binding profile of the secretory epithelium of
      Brunner's glands resembled that of pyloric glands more closely than that of
      duodenal goblet cells and mucous surface cells of the stomach. Mucins from
      Brunner's glands and pyloric glands showed a greater terminal carbohydrate
      residue diversity than those of gastric mucous surface cells or duodenal goblet
      cells. The lectin-binding profile argues for the evolution of similar mucins from
      the epithelia of Brunner's glands and pyloric glands. The greater diversity of
      carbohydrate residues in mucins secreted by Brunner's glands suggests that their
      mucus is more adaptable. This may explain why Brunner's glands metaplasia rather
      than goblet cell metaplasia is seen in the mucosa adjacent to chronic intestinal
      ulcers.

PMID- 15164343
TI  - Geometric morphometric analysis of allometric variation in the mandibular
      morphology of the hominids of Atapuerca, Sima de los Huesos site.
AB  - Allometry is an important factor of morphological integration that contributes to
      the organization of the phenotype and its variation. Variation in the allometric
      shape of the mandible is particularly important in hominid evolution because the
      mandible carries important taxonomic traits. Some of these traits are known to
      covary with size, particularly the retromolar space, symphyseal curvature, and
      position of the mental foramen. The mandible is a well studied system in the
      context of the evolutionary development of complex morphological structures
      because it is composed of different developmental units that are integrated
      within a single bone. In the present study, we investigated the allometric
      variation of two important developmental units that are separated by the inferior
      nerve (a branch of CN V3). We tested the null hypothesis that there would be no
      difference in allometric variation between the two components. Procrustes-based
      geometric morphometrics of 20 two-dimensional (2D) landmarks were analyzed by
      multivariate regressions of shape on size in samples from 121 humans, 48
      chimpanzees, and 50 gorillas (all recent specimens), eight fossil hominids from
      Atapuerca, Sima de los Huesos (AT-SH), and 17 Neandertals. The findings show that
      in all of the examined species, there was significantly greater allometric
      variation in the supra-nerve unit than in the infra-nerve unit. The formation of
      the retromolar space exhibited an allometric relationship with the supra-nerve
      unit in all of the species studied. The formation of the chin-like morphology is
      an "apodynamic" feature of the infra-nerve unit in the AT-SH hominids. The
      results of this study support the hypothesis that allometry contributes to the
      organization of variation in complex morphological structures.

PMID- 15164344
TI  - Craniofacial growth in growth hormone-deficient rats.
AB  - Although supplementation with growth hormone (GH) is an accepted treatment for
      children who are GH-deficient or very small in stature, its effect on the
      craniofacial skeleton has been little studied. The goal of this study was to
      compare the absolute and relative growth of the craniofacial skeleton in GH
      deficient dwarf rats to that in wild-type rats of the same strain, using a mixed
      longitudinal radiographic design. Lateral and dorsoventral X-rays of the head and
      hindlimb were obtained weekly in dwarf and wild-type female Lewis rats from 4 to
      9 weeks of age (n = 14 for each time interval). The X-rays were scanned, 27
      cephalometric points were digitized, and selected linear distances were measured
      between points. Multilevel statistical procedures were used to model growth
      changes in different regions of the head. Among craniofacial measures, growth
      curves of the two groups differed greatly in the magnitude of initial size
      differences and the effect of GH deficiency on growth velocity. Considerable
      variation (65-97%) also existed among craniofacial measures with regard to
      relative maturity (i.e., the percentage of growth completed between the first and
      last time intervals). The deficiency effect (a quantitative estimate of the
      extent to which growth velocity was affected by GH) was negatively correlated (r
      = -0.52, P < 0.01) with relative maturity of a particular measure. The dependence
      of the GH effect on relative maturity suggests that different craniofacial
      morphologies may result depending on the timing of GH supplementation therapy.

PMID- 15164345
TI  - Development of a mammalian series-fibered muscle.
AB  - This study examines the processes by which multiply innervated, serially fibered
      mammalian muscles are constructed during development. We previously reported that
      primary myotubes of such a muscle, the guinea pig sternomastoid muscle, span from
      tendon to tendon and are innervated at each of the muscle's four innervation
      zones. Secondary myotubes form later, in association with each point of
      innervation (Duxson and Sheard, Dev. Dyn., 1995; 204:391-405). We now describe
      the further growth and development of the muscle. Secondary myotubes initially
      insert onto and grow along the primary myotube. However, as they reach a critical
      length, they encounter other secondary myotubes growing from serially adjacent
      innervation zones and may transfer their attachment(s) to these serially
      positioned secondary myotubes. Other secondary myotubes maintain attachment at
      one or both ends to their primary myotube. Thus, an interconnected network of
      primary and secondary myotubes is formed. Patterns of reactivity for cell
      adhesion molecules suggest that early attachment points between myotubes are the
      embryonic precursors of adult myomyonal junctions, characterized by the
      expression of alpha7Bbeta1 integrin. Finally, the results show that secondary
      myotubes positioned near a tendon are generally longer than those lying in the
      mid belly of the muscle, and we suggest that the environment surrounding the
      tendinous zone may somehow stimulate myotube growth.

PMID- 15164346
TI  - Identifying acetylated lignin units in non-wood fibers using pyrolysis-gas
      chromatography/mass spectrometry.
AB  - A series of non-wood plant fibers, namely kenaf, jute, sisal and abaca, have been
      analyzed upon pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) of the
      whole material. The pyrolysis products mainly arise from the carbohydrate and
      lignin moieties of the fibers. The lignin-derived phenols belonged to the p
      hydroxyphenylpropanoid (H), guaiacylpropanoid (G) and syringylpropanoid (S)
      structures, and showed a high S/G ratio of between 2.0 and 5.4, the highest
      corresponding to kenaf. Among the lignin-derived phenols released, small amounts
      of sinapyl and coniferyl acetates (in both cis- and trans-forms) were identified
      for the first time upon Py-GC/MS of lignocellulosic materials. Acetylation of the
      sinapyl and coniferyl alcohols was at the gamma-position of the side chain. The
      release of these alcohols derived from intact acetylated lignin units upon
      pyrolysis seems to indicate that the native lignin in the fibers selected for
      this study is at least partially acetylated. Sinapyl (and coniferyl) acetates
      have recently been suggested to be authentic lignin precursors involved in the
      polymerization of lignin along with the normal sinapyl and coniferyl alcohols. Py
      GC/MS will offer a convenient and rapid tool for analyzing naturally acetylated
      lignins, as well as to screen plant materials for the presence of acetylated
      units in lignin.

PMID- 15164347
TI  - Study of the photoinduced degradation of polycyclic musk compounds by solid-phase
      microextraction and gas chromatography/mass spectrometry.
AB  - Polycyclic musks are widely used synthetic fragrances that have been identified
      during the last few years in biota samples and environmental matrices.
      Nevertheless, there is a lack of information concerning the photodegradation
      behavior of these compounds. In this work, the photoinduced degradation of six
      polycyclic musk compounds (Cashmeran, Celestolide, Phantolide, Galaxolide,
      Traseolide and Tonalide) was studied using a solid-phase microextraction (SPME)
      fiber as support. Musk fragrances were extracted from aqueous solutions using
      SPME fibers that were subsequently exposed to ultraviolet (UV) irradiation for
      different times. To study the degradation kinetics and to tentatively identify
      the photoproducts generated, gas chromatography coupled to ion trap mass
      spectrometry was used. Aqueous photodegradation studies were also performed. The
      on-fiber photodegradation approach avoids the need for further extraction
      processes and makes the identification of photoproducts easier, due to their
      higher concentration on the fibers. All musk compounds were easily photodegraded,
      suggesting that UV irradiation could work as a decontamination tool for these
      musks.

PMID- 15164348
TI  - Electrospray sample deposition for matrix-assisted laser desorption/ionization
      (MALDI) and atmospheric pressure MALDI mass spectrometry with attomole detection
      limits.
AB  - Electrospray sample deposition was explored for matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). In this
      method, nanoliter volumes of matrix/analyte mixture were electrosprayed from a
      high voltage biased (1-2 kV) fused-silica capillary onto a grounded MALDI plate
      mounted 100-500 microm from the capillary outlet. Electrospray deposition with
      these conditions produced sample spots 200-300 microm in diameter thus matching
      the laser spot size. Varying spray voltage and distance resulted in different
      crystal sizes and volatilization rates for alpha-cyano-4-hydroxycinnamic acid
      matrix. Best results were obtained when the sample was deposited as wet droplets
      as opposed to deposition as dried solid. Under 'wet-spray' conditions, 2-4 microm
      diameter crystals were formed and detection limits for several neuropeptides were
      0.7-25 amol. Samples could be pre-concentrated on the plate by spraying
      continuously and allowing sample to evaporate in a small spot. Sample volumes as
      large as 580 nL were deposited yielding a detection limit of 35 pM for
      neurotensin 1-11. Electrospray sample deposition yielded similar results when
      using atmospheric pressure-MALDI coupled with a quadrupole ion trap mass
      spectrometer, except that the sensitivity was approximately seven-fold worse.

PMID- 15164349
TI  - Distinguishing sources of N2O in European grasslands by stable isotope analysis.
AB  - Nitrifiers and denitrifiers are the main producers of the greenhouse gas nitrous
      oxide (N(2)O). Knowledge of the respective contributions of each of these
      microbial groups to N(2)O production is a prerequisite for the development of
      effective mitigation strategies for N(2)O. Often, the differentiation is made by
      the use of inhibitors. Measurements of the natural abundance of the stable
      isotopes of N and O in N(2)O have been suggested as an alternative for the often
      unreliable inhibition studies. Here, we tested the natural abundance incubation
      method developed by Tilsner et al.1 with soils from four European grasslands
      differing in long-term management practices. Emission rates of N(2)O and stable
      isotope natural abundance of N(2)O and mineral N were measured in four different
      soil incubations: a control with 60% water-filled pore space (WFPS), a treatment
      with 60% WFPS and added ammonium (NH(4) (+)) to support nitrifiers, a control
      with 80% WFPS and a treatment with 80% WFPS and added nitrate (NO(3) (-)) to
      support denitrifiers. Decreases in NH(4) (+) concentrations, linked with relative
      (15)N-enrichment of residual NH(4) (+) and production of (15)N-depleted NO(3) (
      ), showed that nitrification was the main process for mineral N conversions. The
      N(2)O production, however, was generally dominated by reduction processes, as
      indicated by the up to 20 times larger N(2)O production under conditions
      favouring denitrification than under conditions favouring nitrification.
      Interestingly, the N(2)O concentration in the incubation atmospheres often
      levelled off or even decreased, accompanied by increases in delta(15)N and
      delta(18)O values of N(2)O. This points to uptake and further reduction of N(2)O
      to N(2), even under conditions with small concentrations of N(2)O in the
      atmosphere. The measurements of the natural abundances of (15)N and (18)O proved
      to be a valuable integral part of the natural abundance incubation method.
      Without these measurements, nitrification would not have been identified as
      essential for mineral N conversions and N(2)O consumption could not have been
      detected.

PMID- 15164350
TI  - Improved method for peak picking in matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - A method for peak picking for matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) is described. The method is based on the
      assumption that two sets of ions are formed during the ionization stage, which
      have Gaussian distributions but different velocity profiles. This gives rise to a
      certain degree of peak skewness. Our algorithm deconvolutes the peak and utilizes
      the fast velocity, bulk ion distribution for peak picking. Evaluation of the
      performance of the new method was conducted using peptide peaks from a bovine
      serum albumin (BSA) digest, and compared with the commercial peak-picking
      algorithms Centroid and SNAP. When using the new two-Gaussian algorithm, for
      strong signals the mass accuracy was equal to or marginally better than the
      results obtained from the commercial algorithms. However, for weak, distorted
      peaks, considerable improvement in both mass accuracy and precision was obtained.
      This improvement should be particularly useful in proteomics, where a lack of
      signal strength is often encountered when dealing with weakly expressed proteins.
      Finally, since the new peak-picking method uses information from the entire
      signal, no adjustments of parameters related to peak height have to be made,
      which simplifies its practical use.

PMID- 15164351
TI  - Characterisation of natural indigo and shellfish purple by mass spectrometric
      techniques.
AB  - Two analytical methods based on mass spectrometry were used in the
      characterisation of constituents of natural indigo prepared from the leaves of
      Indigofera tinctoria, and of shellfish purple prepared from the hypobranchial
      glandular secretions of Murex trunculus, following old recipes. On-line pyrolysis
      gas chromatography in the presence of hexamethyldisilazane followed by mass
      spectrometric analysis (Py-silylation/GC/MS), and direct exposure mass
      spectrometry (DE-MS), were used. Extensive fragmentation of indigoid dyes was
      obtained by Py-silylation/GC/MS. The following molecular markers were
      highlighted, which are useful for identification purposes: 1,2-dihydro-3H-indol-3
      one for indigoid dyes, 1,3-dihydro-2H-indol-2-one for indirubine, and 6-bromo-1,2
      dihydro-3H-indol-3-one for shellfish purple. Using DE-MS, 6,6'dibromoindigotine,
      monobromoindigotine and indigotine were identified as the main components, and
      the presence of tyrindoxyl, one of the dye precursors, was also assessed.

PMID- 15164352
TI  - Gas-phase ligand loss and ligand substitution reactions of platinum(II) complexes
      of tridentate nitrogen donor ligands.
AB  - The source of protons associated with the ligand loss channel of HX((n - 1)+)
      from [Pt(II)(dien)X](n+) (X = Cl, Br and I for n = 1 and X = NC(5)H(5) for n = 2)
      in the gas phase was investigated by deuterium-labelling studies. The results of
      these studies indicate that these protons originate from both the amino groups
      and the carbon backbone of the dien ligand. In some instances (e.g. X = Br and
      I), the protons lost from the carbon backbone can be even more abundant than the
      protons lost from the amino groups. The gas-phase substitution reactions of
      coordinatively saturated [Pt(II)(L(3))L(a)](2+) complexes (L(3) = tpy or dien)
      were also examined using ion-molecule reactions. The outcome of the ion-molecule
      reactions depends on both the ancillary ligand (L(3)) as well as the leaving
      group (L(a)). [Pt(II)(tpy)L(a)](2+) complexes undergo substitution reactions,
      with a faster rate when L(a) is a good leaving group, while the
      [Pt(II)(dien)L(a)](2+) complex undergoes a proton transfer reaction.

PMID- 15164353
TI  - Stable carbon isotope analysis of different tissues of beef animals in relation
      to their diet.
AB  - As part of a larger experiment, 31 young bulls, divided into three groups, were
      given different diets containing either C(3) plants or a combination of C(3) and
      C(4) plant-based feeds in three feeding periods before slaughter. Variation in
      the proportion of C(4) plant material in the diets was made by including or not
      maize or maize-derived ingredients, whereas the other dietary constituents were
      from C(3) plants. Analysis of stable carbon isotope ratios (delta(13)C value) was
      performed on different tissues taken at slaughter: blood, plasma, liver, kidney
      fat, hair, muscle and ruminal contents. Blood and plasma samples were also taken
      at the beginning of each period. A highly significant difference was found in the
      delta(13)C values of blood and plasma samples taken from animals that had
      received a diet of only C(3) plants or with 59% C(4) material for 70 days. The
      delta(13)C values of all different samples taken at slaughter were highly
      significantly different between the three feeding groups that had received diets
      with 0, 13.5 or 35% C(4) material for on average 137, 139 and 83 days,
      respectively. For the three groups, samples of hair, muscle, plasma, whole blood
      and liver were significantly enriched in (13)C compared with the diet (except for
      liver in one group), whereas kidney fat was significantly depleted. The
      proportion of C(4) plant material could be accurately estimated from the
      delta(13)C values of different tissue samples. Stable carbon analysis of
      different tissues from beef animals can be used to trace back diets containing
      variable proportions of C(3) and C(4) plant material.

PMID- 15164355
TI  - A simple method of soil gas stable carbon isotope analysis.

PMID- 15164356
TI  - Detection of chlordecone by liquid chromatography with tandem mass spectrometry.

PMID- 15164354
TI  - Determination of carnitine and acylcarnitines in plasma by high-performance
      liquid chromatography/electrospray ionization ion trap tandem mass spectrometry.
AB  - A high-performance liquid chromatography/mass spectrometry method was developed
      for the determination of carnitine, its biosynthetic precursor butyrobetaine, and
      eight acylcarnitines in plasma. The procedure includes a solid-phase extraction
      for carnitine and short- and medium-chain acylcarnitines, and a liquid-liquid
      extraction for protein-bound long-chain acylcarnitines, followed by separation on
      a reversed-phase column in the presence of a volatile ion-pairing reagent.
      Detection was achieved using an ion-trap mass spectrometer run in the tandem mass
      spectrometry (MS/MS) mode. The choice of the matrix for calibrators, used for
      quantification of these endogenous compounds, was also investigated. Validation
      was performed for standard quality controls diluted with 4% bovine serum albumin
      solution and for spiked plasma quality control samples at concentrations between
      0.5 and 80 micromol/L, depending on the compound. Intra- and inter-day precisions
      for the determination of carnitine were below 3.4% and accuracies were between
      95.2 and 109.0%. Application of the method to the diagnosis of pathological
      acylcarnitine profiles of metabolic disorders in a patient suffering from
      methylmalonic aciduria is presented. The method allows quantification of
      carnitine, butyrobetaine, acetylcarnitine and propionylcarnitine, and
      semiquantitative analysis of medium- and long-chain acylcarnitines. In contrast
      with other methods, no derivatization step is needed.

PMID- 15164357
TI  - High levels of the mitochondrial large ribosomal subunit protein 40 prevent loss
      of mitochondrial DNA in null mmf1 Saccharomyces cerevisiae cells.
AB  - Members of the YERO57c/YJGFc/UK114 protein family have been identified in
      bacteria and eukaryotes. The budding yeast Saccharomyces cerevisiae contains two
      different proteins of this family, Hmf1p and Mmf1p. We have previously shown that
      Mmf1p is a mitochondrial protein functionally related to its human homologue and
      able to influence the maintenance of mitochondrial DNA. Deletion of Mmf1 results
      in loss of the mitochondrial genome. Using a multicopy suppression approach, we
      have identified a protein of the mitochondrial large ribosomal subunit, MRPL40,
      which stabilizes mtDNA in Deltammf1 cells. Overexpression of MRPL40 did not
      prevent loss of mtDNA in a mutant strain lacking the mitochondrial protein Abf2p.
      Thus, MRPL40 does not have a general effect on mtDNA stability, but it may be
      specific for the mmf1-null strain. We also show that the Deltamrpl40 cells
      present a similar phenotype to the mmf1-null strain, having reduced mtDNA
      stability and growth rate. Furthermore, we observed that rho(+)Deltamrpl40
      haploid cells can be obtained when tetrads are directly dissected on medium
      containing a non-fermentable carbon source. Thus, replication and segregation of
      the mtDNA can occur in the absence of MRPL40. We also show that another
      mitochondrial ribosomal protein, MRPL38, is able to overcome the Deltammf1
      associated defect. Together, our results suggest a link between Mmf1p and the two
      mitochondrial ribosomal proteins.

PMID- 15164358
TI  - Yeast involved in fermentation of Coffea arabica in East Africa determined by
      genotyping and by direct denaturating gradient gel electrophoresis.
AB  - Samples of Coffea arabica were collected during the different stages of the
      fermentation from two production sites in Tanzania. The yeasts community was
      identified by genotyping using ITS-PCR and sequence analysis of the D1/D2 domain
      of the 26S rRNA gene. For confirmation, denaturating gradient gel electrophoresis
      (DGGE) of PCR-amplified 26S rRNA gene was performed to detect yeast directly from
      coffee samples without cultivation. Yeast counts were in the range 4.0 x 10(4) -
      5.0 x 10(7) CFU/g with an increase during fermentation. Three yeasts species were
      dominant. The predominant yeast found during fermentation and drying was Pichia
      kluyveri. Pichia anomala was found in high numbers during drying of coffee beans.
      Hanseniaspora uvarum was the predominant yeast during fermentation but decreased
      during drying. Kluyveromyces marxianus, Candida pseudointermedia, Issatchenkia
      orientalis, Pichia ohmeri and Torulaspora delbrueckii occurred in concentrations
      of 10(3) CFU/g or below in coffee samples. Saccharomyces cerevisiae and Candida
      xestobii were not isolated by cultivation, but by the DGGE technique. A good
      agreement was found between the sequence analysis of the D1/D2 domain of the 26S
      rRNA gene and sequencing of the DGGE bands.

PMID- 15164360
TI  - The trehalose pathway and intracellular glucose phosphates as modulators of
      potassium transport and general cation homeostasis in yeast.
AB  - Trk, encoded by the partially redundant genes TRK1 and TRK2, is the major
      potassium transporter of Saccharomyces cerevisiae. This system is specific for
      potassium and rubidium but, by reducing the electrical membrane potential of the
      plasma membrane, Trk decreases the uptake of toxic cations such as lithium,
      calcium, aminoglycosides and polyamines, which are transported by other systems.
      Gain- and loss-of-function studies indicate that TPS1, a gene encoding trehalose
      6-phosphate synthase and known to modulate glucose metabolism, activates Trk and
      reduces the sensitivity of yeast cells to many toxic cations. This effect is
      independent of known regulators of Trk, such as the Hal4 and Hal5 protein kinases
      and the protein phosphatase calcineurin. Mutants defective in isoform 2 of
      phosphoglucomutase (pgm2) and mutants defective in isoform 2 of hexokinase (hxk2)
      exhibit similar phenotypes of reduced Trk activity and increased sensitivity to
      toxic cations compared with tps1 mutants. In all cases Trk activity was
      positively correlated with levels of glucose phosphates (glc-1-P and glc-6-P).
      These results indicate that Tps1, like Pgm2 and Hxk2, increases the levels of
      glucose phosphates and suggest that these metabolites, directly or indirectly,
      activate Trk.

PMID- 15164359
TI  - Candida glabrata Ste20 is involved in maintaining cell wall integrity and
      adaptation to hypertonic stress, and is required for wild-type levels of
      virulence.
AB  - The conserved family of fungal Ste20 p21-activated serine-threonine protein
      kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20
      is involved in pheromone signalling, invasive growth, the hypertonic stress
      response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding
      protein required for polarized morphogenesis. We have cloned the STE20 homologue
      from the fungal pathogen Candida glabrata and have shown that it is present in a
      single copy in the genome. Translation of the nucleotide sequence predicts that
      C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine
      protein kinase domain, a binding site for G-protein beta subunits and a
      regulatory Rho-binding domain that enables the kinase to interact with Cdc42
      and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58%
      predicted amino acid similarity to S. cerevisiae Ste20 and can complement both
      the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae
      ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C.
      glabrata Ste20 is required for a fully functional hypertonic stress response and
      intact cell wall integrity pathway. C. glabrata Ste20 is not required for
      nitrogen starvation-induced filamentation. Survival analysis revealed that C.
      glabrata ste20 mutants, while still able to cause disease, are mildly attenuated
      for virulence compared to reconstituted STE20 cells.

PMID- 15164361
TI  - The use of Yarrowia lipolytica for the expression of human cytochrome P450
      CYP1A1.
AB  - Cytochromes P450 constitute a superfamily of haem-thiolate mono-oxygenases that
      are involved in the oxidative metabolism of lipophilic subtrates. These enzymes
      require association with cytochrome P450 reductase (CPR) to achieve optimal
      activities. We have expressed human cytochrome P450 CYP1A1 under the POX2
      promoter (pPOX2-CYP1A1) in Y. lipolytica, with or without overproduction of Y.
      lipolytica CPR expressed under the ICL promoter (pICL-CPR) or the POX2 promoter
      (pPOX2-CPR). Activity of cytochrome CYP1A1 was analysed by conversion of
      hydroxyresorufin to resorufin. Strain JMY330 and JMY330-CPR present no activity,
      the monocopy cytochrome CYP1A1 integrant JMY331 and JMY331-CPR derivatives
      present an average activity of 32.0 pM/min/dw and 48.3 and 64.6 pM/min/dw for
      pICL-CPR and pPOX2-CPR, respectively. Increase of CPR expression resulted in
      about two-fold higher activity. The multicopy 1A1 integrant JMY339 and JMY339-CPR
      derivatives present an activity of 129 pM/min/dw and 815-1845 pM/min/dw,
      respectively. Increase of CPR expression resulted in 6.3-12.8-fold higher
      activity, depending on the CPR transformant. We observed a 50-fold increase of
      activity between the monocopy integrant JMY331 as compared to the multicopies
      integrant JMY339-CPR in which CPR was overexpressed.

PMID- 15164362
TI  - Transcriptional and post-translational regulation of neutral trehalase in
      Schizosaccharomyces pombe during thermal stress.
AB  - In the fission yeast Schizosaccharomyces pombe, a heat shock enhances
      transcription of the ntp1(+) gene, encoding the hydrolytic enzyme neutral
      trehalase. As compared to wild-type cells, cells devoid of the MAP kinase Sty1p
      showed a strong decrease in ntp1(+) expression induced by the temperature
      upshift, indicating that the stress-activated protein kinase (SAPK) pathway
      regulates the expression of this gene during heat shock. The transcription factor
      Atf1p, which is the main downstream target for Sty1p in the SAPK pathway, appears
      to be involved in such control, since ntp1(+) expression under heat shock proved
      to be significantly blocked in atf1(+)-disrupted cells. Serial deletion and point
      mutation analyses of the ntp1(+) promoter, as well as electrophoretic mobility
      shift assays, revealed the existence of a CRE-like element as the target for
      Atf1p-mediated expression under thermal stress. The relevance of two putative HSE
      elements located in the ntp1(+) promoter was also investigated for their
      potential role in regulating ntp1(+) transcription during heat shock. The results
      support a model in which heat-induced Atf1p binding to the CRE-like element
      favours the subsequent interaction of the heat shock factor (HSF) with HSE
      elements in the ntp1(+) promoter. Unlike what happens under osmostress or
      oxidative treatments, Sty1p has no role in the post-translational activation of
      neutral trehalase induced by heat shock in the fission yeast.

PMID- 15164363
TI  - Ultrastructure of the annual cycle of female sperm storage in spermathecae of the
      torrent salamander, Rhyacotriton variegatus (Amphibia: Rhyacotritonidae).
AB  - This study is the first report on the ultrastructure of the sperm storage glands
      (spermathecae) in the salamander Rhyacotriton variegatus. The population studied
      is associated with cold-water, rocky streams of the redwood (Sequoia) zone in
      northern California. Males possess sperm in their vasa deferentia and undergo
      spermiation throughout the year, but mating is seasonal. Most females with large,
      vitellogenic follicles (2.0-3.9 mm mean dia.) collected from February-June
      contain sperm in their spermathecae, although some females with large follicles
      lack sperm. Other mature-size females collected during this period have small
      ovarian follicles (0.9-1.2 mm mean dia.) and lack stored sperm. All females
      collected from September-November have small follicles (0.6-1.6 mm mean dia.) and
      lack sperm, except in one instance in which a female collected in November had a
      small amount of degraded sperm, apparently retained from the previous breeding
      season. The spermathecae consist of simple tubulo-alveolar glands in which the
      neck tubules produce a mucoid secretory product, and the distal bulbs, where
      sperm are stored, contain secretory vacuoles of uniform density that stain
      positively for glycosaminoglycans. In specimens containing sperm, some bulbs have
      abundant sperm and others lack sperm, but the ultrastructure is similar in both
      conditions. The acini contain columnar epithelial cells with wide intercellular
      canaliculi, and a merocrine process releases the secretion. Spermiophagy occurs.
      In specimens from spring and summer with small ovarian follicles, the neck
      tubules are similar to those of breeding females, but the distal bulbs are
      reduced to cords of cells lacking a discernible lumen. Secretory activity in the
      distal bulbs is initiated in the fall. Spermathecae of R. variegatus are most
      similar to those of a stream-dwelling plethodontid, Eurycea cirrigera.

PMID- 15164364
TI  - Effects of adrenaline administration on the interrenal gland of the newt,
      Triturus carnifex: evidence of intraadrenal paracrine interactions.
AB  - The existence of paracrine control of steroidogenic activity by adrenochromaffin
      cells in Triturus carnifex was investigated by in vivo adrenaline (A)
      administration. The effects were evaluated by examination of the ultrastructural
      morphological and morphometrical features of the tissues as well as the serum
      levels of aldosterone, noradrenaline (NA), and adrenaline. In March and July,
      adrenaline administration reduced aldosterone release (from 187.23 +/- 2.93 pg/ml
      to 32.28 +/- 1.85 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 87.51 +/- 2.57
      pg/ml in July) from steroidogenic cells. The cells showed clear signs of lowered
      activity: they appeared full of lipid, forming large droplets. Moreover,
      adrenaline administration decreased the mean total number of secretory granules
      in the chromaffin cells in July (from 7.74 +/- 0.74 granules/microm(2) to 5.14 +/
      1.55 granules/microm(2)). In this period T. carnifex chromaffin cells contain
      almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm(2); A: 0.32 +/-
      0.13 granules/microm(2)). Adrenaline administration reduced noradrenaline content
      (4.36 +/- 1.40 granules/microm(2)) in the chromaffin cells, enhancing
      noradrenaline secretion (from 640.19 +/- 1.65 pg/ml to 1030.16 +/- 3.03 pg/ml).
      In March, adrenaline administration did not affect the mean total number of
      secretory vesicles (from 7.24 +/- 0.18 granules/microm(2) to 7.25 +/- 1.97
      granules/microm(2)). In this period the chromaffin cells contain both
      catecholamines, noradrenaline (3.88 +/- 0.13 granules/microm(2)), and adrenaline
      (3.36 +/- 0.05 granules/microm(2)), in almost equal quantities; adrenaline
      administration reduced adrenaline content (1.74 +/- 0.84 granules/microm(2)),
      increasing adrenaline release (from 681.27 +/- 1.83 pg/ml to 951.77 +/- 4.11
      pg/ml). The results of this study indicate that adrenaline influences the
      steroidogenic cells, inhibiting aldosterone release. Adrenaline effects on the
      chromaffin cells (increase of noradrenaline or adrenaline secretion) vary
      according to the period of chromaffin cell functional cycle. The existence of
      intraadrenal paracrine interactions in T. carnifex is discussed.

PMID- 15164365
TI  - Embryonic development of the oligochaete Enchytraeus coronatus: an SEM and
      histological study of embryogenesis from one-cell stage to hatching.
AB  - We describe the embryonic development of the soil-living oligochaete Enchytraeus
      coronatus (Enchytraeidae, Oligochaeta, Annelida). Enchytraeus coronatus is a
      direct developer. It follows the typical spiral cleavage mode of development that
      is highly conserved among annelids and a large number of other lophotrochozoan
      taxa that are collectively named "Spiralia." Scanning electron microscopy (SEM)
      was combined with light microscopic analysis of wholemounted and sectioned
      embryos, differentially processed through histological stainings, to reconstruct
      and document cellular movements and organogenesis from early cleavage stages
      until hatching. With the help of these data we have established a scheme of
      morphologically defined stages in order to facilitate future studies on the
      molecular and histological level that will allow a detailed cross-species
      comparison among annelids and other phyla.

PMID- 15164367
TI  - The spermatozoon of Eurasian murine rodents: Its morphological diversity and
      evolution.
AB  - The murine rodents are the most speciose subfamily of mammals. Here the
      morphology of the spermatozoon, as determined by scanning and transmission
      electron microscopy of representative species from four Eurasian clades, is
      described. Much interspecific variability in all components of the spermatozoon
      was found to occur, although most species have a bilaterally flattened sperm head
      with a single apical hook of variable length and orientation. Ultrastructural
      observations indicate that this apical hook invariably contains a nuclear
      projection as well as a large extension of the subacrosomal cytoskeleton, as a
      perforatorium rostrally, and a complex asymmetrical acrosomal extension. These
      spermatozoa also have relatively long tails that are attached to the lower
      concave surface of the sperm head. Uniquely, in species in the Apodemus clade,
      the apical hook is orientated caudally. In a few species a highly derived sperm
      head morphotype that does not contain an apical hook is present. These sperm
      heads vary in morphology from being globular in two species of Bandicota, to
      bilaterally flattened and paddle-shaped in Tokudaia and Micromys. In spermatozoa
      of the latter two genera the subacrosomal cytoskeleton, which is less extensive
      than in species with a hooked sperm head, forms an apical extension, but that is
      not the case in Bandicota. In all species where the sperm head lacks an apical
      hook the acrosome is more symmetrical. The sperm tail is much shorter in these
      species, with attachment to the head occurring on the ventral surface in Tokudaia
      and basal in Micromys and the two species of Bandicota. As the sperm head
      morphotype with a complex apical hook is present in all the major clades of
      murine rodents, it is likely to be a plesiomorphic character within each of these
      clades, with the nonhooked sperm heads, which vary greatly in structure between
      species of the different lineages, probably being independently derived. The
      ultrastructural organization of the sperm head of Bandicota, but not those of
      Micromys or Tokudaia, suggest divergence in some of the morphological events
      associated with sperm-egg interaction at the time of fertilization.

PMID- 15164366
TI  - Infraciliature and myoneme system of Campanella umbellaria (Protozoa, Ciliophora,
      Peritrichida).
AB  - The infraciliature and myoneme system of Campanella umbellaria were revealed
      using the protargol impregnation technique. The main characteristics of the
      infraciliature are the peristomial ciliary rows (haplokinety and polykineties),
      which make four and a half turns around the peristomial disc before plunging into
      the infundibulum, and the aboral infraciliature, which is made up of the aboral
      ciliary wreath (trochal band) and the scopula. The myoneme system is composed of:
      1) longitudinal fibers, which include 60-84 (mean 72.3) short longitudinal
      fibers, 40-56 (mean 45.8) medium-length longitudinal fibers, and numerous long
      longitudinal fibers; and 2) circular fibers, which include 8-12 (mean 9.3)
      peristomial ring fibers, linking fibers, support fibers, and peristomial disc
      fibers. The various fibers in C. umbellaria are interconnected to form a single
      myoneme system that may act as a cell skeleton as well as providing the mechanism
      by which the zooid contracts and relaxes.

PMID- 15164368
TI  - Variation in seasonal ultrastructure of sexual granules in the renal sexual
      segment of the Northern Water Snake, Nerodia sipedon sipedon.
AB  - The renal sexual segment of the kidney (RSS) can be found in many male squamate
      reptiles, encompassing the distal region of the nephron and, in some cases,
      collecting ducts. This sexually dimorphic structure exhibits varying degrees of
      hypertrophy and regression throughout the year. Although researchers have been
      aware of and have investigated this unique structure for over a century, its
      ultimate function remains under discussion. In many studies hypertrophy and
      regression of the RSS have been correlated with testicular activity and androgen
      secretion. As in most of the snakes studied to date, the male Northern Water
      Snake (Nerodia s. sipedon) does not exhibit a dramatic cycle of hypertrophy and
      regression, as reported in lizards. Following the initial hypertrophy at
      maturity, the male Northern Water Snake maintains a level of RSS hypertrophy
      throughout the year. Variations in the appearance and makeup of the sexual
      granules provide an identifiable and quantifiable seasonal pattern that can be
      correlated with the concentration of plasma androgens. In the Northern Water
      Snake, plasma androgens are elevated upon emergence and the RSS epithelial cells
      are filled with solid granules. As androgen levels decline during spring, sexual
      granule content appears to be breaking down (utilized?), becoming diffuse in
      appearance. By mid- to late summer androgen synthesis is at a maximum, increasing
      circulating androgens and stimulating the development and return of the solid
      granules. This study utilized electron microscopy and steroid radioimmunoassay to
      examine seasonal cycles of sex granules, in terms of development, maintenance,
      and regression, correlated with plasma androgen concentration. In addition, this
      investigation provides evidence of a possible secondary source of androgen
      secretion.

PMID- 15164369
TI  - Morphometric analysis of the larval branchial chamber in the dragonfly Aeshna
      cyanea Muller (Insecta, Odonata, Anisoptera).
AB  - The aquatic larvae of anisopteran dragonflies possess tracheal gills located in
      the rectum. Using stereological methods, we estimated the morphometric diffusing
      capacity for oxygen (D(MO2)) across the gill epithelium, i.e., from rectal water
      to the gill tracheoles, in the larvae of Aeshna cyanea. A 271-mg larva has a
      total branchial surface area of approximately 12 cm(2). Tracheoles make up 6% of
      the epithelial volume of the gills; the harmonic mean thickness of the water
      tracheolar diffusion barrier is 0.27 microm and consists mainly of cuticle. The
      calculated D(MO2) is 23.0 microl min(-1) g(-1) kPa(-1), which, using published
      values for oxygen consumption in a similar species, would result in a mean
      driving pressure of 0.2 kPa at rest and 1.3 kPa during activity. Since these
      driving pressures are similar to those reported for other arthropods, we conclude
      that the D(MO2) of the gill is not rate-limiting for aerobic metabolism in Aeshna
      cyanea larvae. J Morphol. 261:81-91, 2004.

PMID- 15164370
TI  - Stages in spermatogenesis of two species of caecilians, Ichthyophis tricolor and
      Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): Light and electron microscopic
      study.
AB  - The sequential changes during spermatogenesis in the testis of two species of
      caecilians, Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani
      (Uraeotyphliidae), of Western Ghats of Kerala, India, were traced using both
      histological techniques and transmission electron microscopy. The cell nests were
      assigned to stages in spermatogenesis based on the classification of van Oordt
      (1956, Thesis, Utrecht University). To the best of our knowledge, this is the
      first identification and ultrastructural description of stages in spermatogenesis
      in caecilians. The article illustrates not only the stages, but also the cell
      divisions, mitotic and meiotic, as specified. The observations indicate that,
      although caecilians have undergone considerable modifications in morphology and
      anatomy, including reproductive anatomy, in the context of a subterranean and
      concealed life, they appear to have conserved the typical amphibian pattern of
      spermatogenesis for the events of development of spermatids.

PMID- 15164371
TI  - Structural fiber reinforcement of keel blubber in harbor porpoise (Phocoena
      phocoena).
AB  - This study investigated the functional morphology of the blubber that forms the
      caudal keels of the harbor porpoise (Phocoena phocoena). Blubber is a pliant
      biocomposite formed by adipocytes and structural fibers composed of collagen and
      elastic fibers. Caudal keels are dorsally and ventrally placed triangular wedges
      of blubber that define the hydrodynamic profile of the porpoise tailstock.
      Mechanical tests on carcasses demonstrate that when keels are bent, they strain
      nonuniformly along their lengths, with highest strains just caudal to the dorsal
      fin and lowest at the insertion of the flukes. Therefore, caudal keels undergo
      nonuniform longitudinal deformation while maintaining a stable, triangular cross
      sectional shape. Polarizing and transmitted light microscopy techniques were used
      to investigate blubber's 3D fiber architecture along the length of the dorsal
      keel. The triangular cross-sectional shape of the keel appears to be maintained
      by structural fibers oriented to act as tensile stays. The construction of the
      blubber composite is regionally specific :structural fiber densities and
      diameters are higher in the relatively stiff caudal region of the keel than in
      the more deformable cranial keel region. The orientations of structural fibers
      also change along the length of the keel. Cranially, no fibers are oriented along
      the long axis, whereas a novel population of longitudinally oriented fibers
      reinforces the keel at the insertion of the flukes. Thus, differences in the
      distribution and orientation of structural fibers contribute to the regionally
      specific mechanical properties of the dorsal keel.

PMID- 15164372
TI  - Three-dimensional model of the feline hindlimb.
AB  - This article describes a three-dimensional musculoskeletal model of the feline
      hindlimb based on digitized musculoskeletal anatomy. The model consists of seven
      degrees of freedom: three at the hip and two each at the knee and ankle. Lines of
      action and via points for 32 major muscles of the limb are described.
      Interspecimen variability of muscle paths was surprisingly low; most via points
      displayed a scatter of only a few millimeters. Joint axes identified by
      mechanical techniques as noncoincident and nonorthogonal were further honed to
      yield moment arms consistent with previous reports. Interspecimen variability in
      joint axes was greater than that of muscle paths and highlights the importance of
      joint axes in kinematic models. The contribution of specific muscles to the
      direction of endpoint force generation is discussed.

PMID- 15164373
TI  - The older sickle cell patient.
AB  - The lifespan of sickle cell patients has increased substantially. We chose to
      compare the attributes of older sickle cell patients with younger ones within the
      confines of a single institutional study serving the local Bronx population.
      Laboratory and clinical assessments from 40 patients with sickle cell disease
      over 40 years of age were compared to 40 patients under 30 years of age. When the
      older group was compared to the younger group, hemoglobin, indirect bilirubin,
      and platelet counts were significantly lower. Creatinine clearances were lower
      and BUN levels were higher in the older group. Although the prevalence of
      radiographically measured cardiomegaly was significantly higher in the older
      group, systolic and diastolic blood pressures remained unchanged. The number of
      crises and number of admissions were higher in the younger group than in the
      older, but there was wide variation, and no significant differences could be
      detected; days spent in hospital over the previous 2 years did not differ. No
      statistically significant differences were observed for absolute reticulocyte
      count, MCV, % HbF, white cell count, liver function tests, or oxygen saturation.
      Comparing genders within age groups, younger males had higher hemoglobin levels
      and absolute reticulocyte counts than younger females, while only the older
      females had higher HbF levels than the corresponding males. Lower levels of
      hemoglobin associated with older age may reflect decreased hematopoietic
      potential that may in part be due to decreased renal function. Lower platelet
      counts in older sickle cell patients may be a consequence of this decreased
      hematopoietic potential but may also represent a secondary survival benefit
      effect in sickle cell anemia.

PMID- 15164374
TI  - Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood
      cell survival.
AB  - A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is
      thought to result from increased RBC turnover, RBC survival has not been
      determined in subjects receiving RBV due to the complexity of the techniques
      commonly used to quantitate RBC life span. We recently described a simple, rapid,
      non-invasive technique that utilizes measurements of alveolar carbon monoxide
      (CO) concentration to determine RBC survival. In the present report, this method
      was employed to assess RBC survival in patients receiving RBV for hepatitis C.
      Each of the 31 measurements of RBC survival in 12 subjects with RBV-associated
      anemia was below the lower limit of normal (77 days), and the average survival
      (46 +/- 14 days) in these subjects was only about 38% of that of healthy controls
      (122 +/- 23 days). Five hepatitis C patients not undergoing RBV treatment had
      normal RBC survivals (112 +/- 17 days). While the mean reticulocyte percentage
      was significantly elevated in subjects treated with RBV, 59% of these
      measurements fell within the limits of normal. We conclude that RBV-associated
      anemia consistently is associated with reduced RBC survival as determined from
      breath CO measurements and that this reduced survival frequently is not
      associated with an elevated reticulocyte count.

PMID- 15164376
TI  - Determinants of ELISA D-dimer sensitivity for unstable angina pectoris as defined
      by coronary catheterization.
AB  - Unstable angina pectoris is associated with elevated D-dimer levels. However, the
      operating characteristics (sensitivity, specificity, positive and negative
      predictive value) of the D-dimer assay for the diagnosis of coronary artery
      disease (CAD) are unknown. Using a prospective, observational design, we
      collected blood from 54 patients with unstable angina pectoris at admission and
      assayed for ELISA D-dimer levels. The sensitivity, specificity, and negative and
      positive prediction values for angiographically determined coronary artery
      disease were calculated at multiple discriminate levels. All patients underwent
      coronary catheterization. A statistically significant correlation was noted
      between ELISA D-dimer levels and age, male sex, hypertension, use of beta
      blocker, fibrinogen levels and catheterization findings. No correlation was noted
      between ELISA D-dimer levels and degree of the coronary artery disease. Best
      results were provided at a discriminate level of 270 ng/ml, with sensitivity 70%,
      negative predictive value 72%, and overall accuracy 67%. All discriminate levels,
      however, provided values too low for diagnosis. In conclusion, ELISA D-dimer
      assay is a non-sensitive, non-specific test for coronary artery disease as
      defined by coronary catheterization. However, the assay adds information
      regarding the severity of disease in patients presenting with acute coronary
      syndrome.

PMID- 15164375
TI  - Mild hyperhomocysteinemia in adult patients with sickle cell disease: a common
      finding unrelated to folate and cobalamin status.
AB  - Homocysteine has associations with both vitamin insufficiency and vascular
      complications, and its status is therefore of interest in sickle cell disease
      (SCD). However, information is limited, especially in adults. We studied plasma
      total homocysteine (tHcy) and three of its major modifiers, cobalamin, folate,
      and creatinine, in 90 adult patients with SCD and 76 control subjects. The
      patients had higher tHcy levels than did controls (P = 0.03) and had elevated
      tHcy more often (20% vs. 3%, P = 0.0005). None of the hyperhomocysteinemic
      patients had low cobalamin or folate levels; on the contrary, patients with SCD
      had high folate levels more often than control subjects (32% vs. 7%; P < 0.0001).
      Although serum creatinine values were lower in SCD patients than in control
      subjects (P = 0.03), high levels also tended to occur more often (8% vs. 1%; P =
      0.054). Most importantly, creatinine levels correlated significantly with tHcy (P
      < 0.0001) and logistic regression analyses showed creatinine to be the only
      significant predictor of high tHcy levels in SCD (P = 0.01). Our results show
      that hyperhomocysteinemia affects 20% of adults with SCD despite routine folate
      supplementation and is independent of folate and cobalamin status. Creatinine was
      the major identifiable influence on tHcy, but renal insufficiency explained only
      4 of the 18 elevated tHcy levels. Longitudinal studies will be needed to
      determine whether the frequent hyperhomocysteinemia of SCD influences the
      vascular complications in SCD. If reducing tHcy becomes advisable, then
      interventions other than folate therapy will be needed.

PMID- 15164377
TI  - Inflammatory potential of neutrophils detected in sickle cell disease.
AB  - An early event in the inflammatory response is neutrophil recruitment to
      endothelium in response to chemotactic stimulation, which in turn activates CD18
      integrin, which anchors neutrophils to the vessel wall under the shear force of
      blood flow. Activated neutrophils circulating in sickle cell disease (SCD)
      patients may significantly contribute to vascular occlusions (VOC) as neutrophils
      adherent to inflamed endothelium recruit sickle red blood cells inducing VOC. To
      elucidate the mechanisms by which neutrophils may participate in VOC in SCD, CD18
      integrin expression and function in fresh blood samples of non-crisis patients
      were measured by flow cytometry. CD11b/CD18 membrane expression was approximately
      70% higher on unstimulated SCD neutrophils than controls, which correlated with a
      1-fold higher rate of adhesion to ligand. Unstimulated SCD neutrophils expressed
      approximately 30,000 active CD18 per cell, while controls expressed approximately
      6,000. Stimulation with a low concentration of IL-8 (0.1 nM) upregulated 100%
      more active CD18 and induced 60% more adhesion of SCD than control neutrophils.
      These data demonstrate that neutrophils from SCD patients constitutively express
      active CD18 in blood and respond with enhanced sensitivity to chemokine
      activation of adhesion, thus increasing their propensity for exuberant adhesion.

PMID- 15164379
TI  - Cutaneous ulcers: An unusual manifestation of inherited thrombophilia.
AB  - We report two cases with cutaneous lesions found to be associated with factor V
      Leiden mutation and low S protein levels. At the time of presentation, no other
      symptoms were reported. Histopathology of both lesions revealed the presence of
      widespread intravascular thrombi. The therapeutic response to oral anticoagulants
      in the first case was dramatic, leading to complete healing of the lesions.
      Inherited causes of thrombophilia manifested as cutaneous lesions, although rare,
      should be considered in the differential diagnosis of occlusive vasculopathy.

PMID- 15164378
TI  - Acute basophilic leukemia: case report.
AB  - The term "basophilic leukemia" has been in use for 75 years. However, consistent
      diagnostic criteria are lacking. This is due to the rarity of the disease and to
      the routine unavailability of special tests that are often required to confirm a
      diagnosis. We report an unusual case of acute basophilic leukemia in a child who
      was referred to our Center, arriving with partially treated acute lymphoblastic
      leukemia. Basophilic differentiation on light microscopy was evident from the
      coarse basophilic granules in blasts, a progressive maturation of blasts toward
      basophils, and toluidine positivity on cytochemistry. Blasts showed a myeloid
      immunophenotype (CD13+, CD33+, CD117+) with a characteristic dual positivity for
      CD34 and CD25, highly suggestive of basophilic nature of the blasts. Conventional
      cytogenetic studies revealed translocation t(8;21)(q22;q22). A diagnosis of acute
      basophilic leukemia with t(8;21) was made. Review of pre-therapy slides showed
      features consistent with AML-M2 with basophilia. There were no basophilic blasts.
      With these features, a diagnosis of acute basophilic leukemia secondary to AML-M2
      was made. In our patient, basophilic leukemia appears to have evolved from
      selective clonal proliferation of "basophil-committed blasts" during the course
      of the disease in a case of AML-M2 with basophilia.

PMID- 15164380
TI  - Thromboembolic complications after splenectomy for hematologic diseases.
AB  - Thromboembolic complications following splenectomy for hematologic diseases occur
      in up to 10% of patients and may range from portal vein thrombosis (PVT) to
      pulmonary embolism (PE) and deep vein thrombosis (DVT). Up to now there exist no
      recommendations for the duration and intensity of prophylactic anticoagulation,
      which usually follows local institutional protocols. We report on three
      consecutive patients with severe portal vein thrombosis and/or pulmonary embolism
      -one with fatal outcome--7 to 35 days after splenectomy for autoimmune hemolytic
      anemia, immunothrombocytopenia, and indolent lymphoma, respectively. Incidence
      and pathophysiology of thromboembolic events (TE) in this patient group as well
      as prophylactic anticoagulation will be discussed, including a review of the
      current literature on this topic.

PMID- 15164381
TI  - Vulvar cancer in a patient with Fanconi's anemia, treated with 3D conformal
      radiotherapy.
AB  - Fanconi's anemia (FA) is rare autosomal recessive disorder characterized by
      aplastic anemia, congenital anomalies, and cancer susceptibility. FA patients
      have deficiencies in DNA repair pathways that cause cellular sensitivity to
      ionizing radiation and cross-link agents such as mitomycin C and diepoxybutane
      (DEB). If these patients survive until early adulthood, they are at high risk for
      developing solid tumors, most commonly squamous cell carcinoma of the oropharynx,
      esophagus, and vulva. Treatment of these solid tumors with radiotherapy is
      complicated by the increased risk of normal tissue toxicity. Three-dimensional
      (3D) conformal radiotherapy is a technique that uses CT images to more accurately
      target tumors and maximize the dose to the tumor volume while limiting the dose
      to normal tissue. This report describes application of 3D conformal radiotherapy
      techniques to the treatment of vulvar cancer in a patient with FA in an attempt
      to limit the normal tissue volume exposed to radiation.

PMID- 15164382
TI  - Successful anti-CD20 monoclonal antibody treatment of severe autoimmune hemolytic
      anemia due to warm reactive IgM autoantibody in a child with common variable
      immunodeficiency.
AB  - Autoimmune hemolytic anemia due to warm reactive IgM autoantibodies is unusual,
      severe, and often fails to respond to standard immunosuppressive therapies in
      both adults and children. A 6-year-old girl with common variable immunodeficiency
      had longstanding steroid dependent, splenectomy-unresponsive, warm IgM
      autoantibody-mediated autoimmune hemolytic anemia. Rituximab, a monoclonal
      antibody directed against CD20 antigen, was used to deplete B lymphocytes and
      reduce autoantibody production. She received a total of six doses of rituximab
      (375 mg/m2). Therapy was well tolerated, and B-lymphocytes were effectively
      depleted from the peripheral blood. The patient was completely tapered off
      glucocorticoids. The patient has remained off immunosuppressive agents for 16
      months despite the return of B lymphocytes to the peripheral circulation. She
      continues to require IVIG. Early treatment with rituximab might be an option for
      patients with warm reactive IgM autoantibody-mediated autoimmune hemolytic anemia
      not responding to other treatments or experiencing untoward side effects from
      those treatments.

PMID- 15164383
TI  - Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus-6 (HHV-6)
      reactivation in an adult receiving high-dose melphalan with autologous peripheral
      stem cell transplantation.
AB  - We report an adult autologous stem cell transplant (ASCT) patient who developed
      transplant-associated thrombotic microangiopathy (TMA) due to human herpesvirus-6
      (HHV-6) reactivation. A 58-year-old female with Stage IIIA IgGkappa multiple
      myeloma received a melphalan (200 mg/m2) ASCT with discharge home after
      resolution of ASCT-related toxicities. She presented on D+20 with dyspnea, rash,
      and fever to 105 degrees F, followed by worsening dyspnea, hypotension, and
      capillary leak. Mental status (MS) changes were noted on D+23, but head CT and
      EEG were unremarkable. On D+29, a generalized seizure occurred with decline in
      platelet count and haptoglobin. TMA was noted on peripheral blood smear and
      therapeutic plasma exchange (TPE) was initiated on D+31. Lumbar puncture (LP)
      revealed CSF protein 74 mg/dL and white blood count 7,000/mm3 with 74%
      lymphocytosis. TPE was continued without improvement in her MS or
      thrombocytopenia despite improvement in microangiopathy. An MRI of the brain
      showed a left hippocampus abnormality, and an EEG was consistent with
      encephalopathy. Serum polymerase chain regimen (PCR) was negative for CMV, HSV1,
      and HSV2 but was strongly positive for HHV-6. Repeat LP protein was 597 mg/dL.
      Foscarnet was initiated, and cerebrospinal fluid (CSF) PCR for HHV-6 revealed
      1,400 DNA copies/mL. Her MS greatly improved within 48 hr of antiviral therapy,
      serum HHV-6 became negative, and TPE was tapered without recurrence of her TMA.
      TMA with HHV-6 reactivation is likely an underdiagnosed entity. Given its
      fulminant course and favorable response to therapy, HHV-6 reactivation should be
      considered a potential etiology in patients with TMA after ASCT.

PMID- 15164384
TI  - Molecular basis of inherited antithrombin deficiency in Portuguese families:
      identification of genetic alterations and screening for additional thrombotic
      risk factors.
AB  - Antithrombin (AT), the most important coagulation serine proteases inhibitor,
      plays an important role in maintaining the hemostatic balance. Inherited AT
      deficiency, mainly characterized by predisposition to recurrent venous
      thromboembolism, is transmitted in an autosomal dominant manner. In this study,
      we analyzed the underlying genetic alterations in 12 unrelated Portuguese
      thrombophilic families with AT deficiency. At the same time, the modulating
      effect of the FV Leiden mutation, PT 20210A, PAI-1 4G, and MTHFR 677T allelic
      variants, on the thrombotic risk of AT deficient patients was also evaluated.
      Three novel frameshift alterations, a 4-bp deletion in exon 4 and two 1-bp
      insertions in exon 6, were identified in six unrelated type I AT deficient
      families. A novel missense mutation in exon 3a, which changes the highly
      conserved F147 residue, and a novel splice site mutation in the invariant
      acceptor AG dinucleotide of intron 2 were also identified in unrelated type I AT
      deficient families. In addition to these, two previously reported missense
      mutations changing the AT reactive site bond (R393-S394) and leading to type II
      RS deficiency, and a previously reported cryptic splice site mutation (IVS4-14G-
      >A), were also identified. In these families, increased thrombotic risk
      associated with co-inheritance of the FV Leiden mutation and of the PAI-1 4G
      variant was also observed. In conclusion, we present the first data regarding the
      underlying genetic alterations in Portuguese thrombophilic families with AT
      deficiency, and confirm that the FV Leiden mutation and probably the PAI-1 4G
      variant represent additional thrombotic risk factors in these families.

PMID- 15164385
TI  - Hemophagocytic syndrome associated with retinoic acid syndrome in acute
      promyelocytic leukemia.
AB  - A 56-year-old woman with an acute promyelocytic leukemia (APL) developed a severe
      all-trans-retinoic (ATRA) syndrome on day 17 of treatment. Shortly after, she
      presented a picture of pancytopenia, hepatosplenomegaly, increased triglycerides,
      ferritin, and liver enzymes. A bone marrow biopsy showed abundant macrophages and
      no evidence of leukemia. Tests for secondary hemophagocytic syndrome (HPS) were
      negative. A diagnosis of HPS was made. Treatment with dexamethasone and high-dose
      immunoglobulins was unsuccessful. Consolidation chemotherapy with idarubicin and
      ATRA rapidly reversed the HPS. The HPS in this patient could be related to the
      release of macrophage-stimulating cytokines by APL cells during ATRA syndrome.

PMID- 15164386
TI  - Warfarin-induced limb gangrene in the setting of lung adenocarcinoma.
AB  - A 53-year-old man with lung adenocarcinoma developed pulmonary embolism and
      bilateral popliteal venous thrombosis. Treated with intravenous unfractionated
      heparin and discharged home on warfarin, he returned a week later with extending
      thrombosis. Treatment with heparin followed by warfarin was reinitiated. Twenty
      four hours following the re-administration of warfarin, the patient's INR
      increased to 14.5. The platelet count dropped by more than 50%, and he developed
      venous limb gangrene of the left leg and skin necrosis of the right leg. Heparin
      induced thrombocytopenia was ruled out, and coagulation studies showed a severe
      depletion of protein C as well as increased thrombin generation. The patient was
      transfused with fresh frozen plasma, and vitamin K was given. Heparin was
      continued, and after 4 weeks, the patient improved markedly showing only minimal
      necrosis of the toes. Venous limb gangrene is a major complication associated
      with warfarin therapy. Its pathogenesis is explained by a transient
      hypercoagulable state produced by protein C depletion that leads to microvascular
      thrombi progressing to venous limb gangrene. The present case emphasizes the
      importance of careful anticoagulation with heparin followed by slow initiation of
      low-dose warfarin, in order to minimize thrombotic complications.

PMID- 15164388
TI  - Solitary plasmacytoma of the duodenum.

PMID- 15164387
TI  - Ablation of hemophilic FVIII inhibitors with FVIII priming, cyclophosphamide
      immune suppression, and rapid tapering of FVIII immune tolerance.
AB  - The efficacy and toxicity of factor VIII (FVIII) priming, cyclophosphamide immune
      suppression, and rapid tapering of concurrent FVIII immune tolerance for subjects
      with hemophilic inhibitors were evaluated. Four subjects with hemophilic
      inhibitors were studied. Before treatment, inhibitors were present for a median
      of 8 months (mean 13 +/- 14.0 months). The median FVIII inhibitor titer was 16
      BU/mL (mean 27.2 +/- 29.2 BU/mL). Following FVIII priming (80.0 +/- 70.2 U/kg),
      subjects received cyclophosphamide 1,418 +/- 636 mg/M2 i.v. q3 weeks for 4.4 +/-
      1.7 courses. Subjects concurrently received a low (6 U/kg/day), moderate (30
      U/kg/day), or high (100 U/kg/day) dose of FVIII followed by a rapid taper as the
      inhibitor titer decreased or resolved. During treatment, the inhibitor titer
      initially increased but then rapidly declined. Inhibitors resolved in 3.9 +/- 2.9
      months. One inhibitor recurred at 2.8 years, but it was successfully re-treated.
      Effectiveness did not depend on the FVIII dose. Toxicity was minimal.
      Cyclophosphamide (1,400 mg/M2) administered after a priming dose of FVIII (80
      U/kg) i.v. q3 weeks for 2-6 cycles with a rapid taper of concurrently
      administered daily FVIII as the inhibitor titer falls is an effective approach to
      hemophilic inhibitor ablation.

PMID- 15164390
TI  - Management of acute chest wall sickle cell pain with nebulized morphine.
AB  - This paper describes, for the first time, the utilization of nebulized morphine
      in the management of severe chest pain in two young adult African-American
      patients who suffered from generalized acute sickle cell painful episodes. While
      hospitalized, both patients developed new sharp chest wall pain, and were treated
      with nebulized morphine started at 20 mg MOSO4 in 3.0- to 5.0-mL physiologic
      buffered saline solution. Within minutes, both patients reported significant
      relief of chest wall pain. Patient 1 achieved 90% pain relief as well as a
      significant decrease in the pain intensity score. Patient 2 reported 40% pain
      relief, and the pain intensity score decreased to a mean of 5.6/10. Hence,
      treatment every 6 hr was continued for 10 days, after which the chest wall pain
      subsided. These findings indicate that nebulized morphine may prove effective in
      the management of acute chest pain in patients with sickle cell anemia. This is a
      desirable alternative in patients with difficult venous access and may more
      specifically target chest pain.

PMID- 15164389
TI  - Hemophagocytic syndrome as a presenting sign of transformation of smoldering to
      acute adult T-cell leukemia/lymphoma: efficacy of anti-retroviral and interferon
      therapy.
AB  - A 55-year-old Caribbean woman with a 6-year history of smoldering adult T-cell
      leukemia/lymphoma presented with clinical and biological symptoms of
      hemophagocytic syndrome. An extensive search for infectious diseases was
      negative. A lymph node biopsy showing large T-cell lymphoma (CD4-, CD25+) and
      findings of high LDH count and severe lymphocytosis led to the diagnosis of acute
      adult T-cell leukemia/lymphoma. Anti-retroviral therapy combining zidovudine,
      lamivudine, and interferon-alpha was started, resulting in rapid control of both
      hemophagocytic syndrome and symptoms of acute adult T-cell leukemia/lymphoma.
      Thus, we propose that adult T-cell leukemia/lymphoma must be added to the
      spectrum of etiologies of hemophagocytic syndrome.

PMID- 15164391
TI  - Topical GM-CSF hastens healing of leg ulcers in sickle cell disease.

PMID- 15164392
TI  - Occupational exposure to diesel and gasoline engine exhausts and risk of lung
      cancer among Finnish workers.
AB  - BACKGROUND: Studies on engine exhausts and lung cancer have given inconsistent
      results. METHODS: Economically active Finns were followed-up for lung cancer
      during 1971-95 (33,664 cases). Their Census occupations in 1970 were converted to
      exposures to diesel and gasoline engine exhausts with a job-exposure matrix. The
      relative risks (RRs) for cumulative exposure (CE) were defined by Poisson
      regression, adjusted for smoking, asbestos, and quartz dust exposure, and
      socioeconomic status. RESULTS: RR for engine exhausts among men did not increase
      with increasing CE. In women, RR for gasoline engine exhaust was 1.58 (95% CI
      1.10-2.26) in the CE-category of 1-99 mg/m(3)-y and 1.66 (1.11-2.50) among those
      with > or =100 mg/m(3)-y (lag 20 years). With a lag of 10 years RR for the
      middle/highest diesel exhaust category in women was 1.42 (0.94-2.13).
      CONCLUSIONS: Occupational exposure to engine exhausts was not consistently
      associated with lung cancer in this study, possibly due to low exposure levels.

PMID- 15164393
TI  - Risk behaviors for pesticide exposure among pregnant women living in farmworker
      households in Salinas, California.
AB  - BACKGROUND: Farmworkers and their families are at risk for pesticide exposure,
      however, little is known about behaviors that increase their risk. We determined
      the frequency of risky behaviors among pregnant farmworkers and characterized
      those at greatest risk. METHODS: Participants included 153 pregnant farmworkers
      and 248 pregnant non-farmworkers who resided with farmworkers from the CHAMACOS
      (Center for the Health Assessment of Mothers and Children of Salinas) study. We
      examined risky behaviors relating to handwashing, bathing, protective clothing,
      house cleaning, laundering of work clothes, wearing of work clothes and shoes
      into the home, and eating produce from the fields. RESULTS: Between 25 and 60% of
      women demonstrated risky behavior on each item. Practices of households with
      pregnant farmworkers and non-farmworkers did not differ. Women who lived in the
      United States longer, and in crowded households demonstrated the most risky
      behavior overall. CONCLUSIONS: Pregnant farmworkers and those living with
      farmworkers need to be educated to reduce potential take-home pesticide exposure.

PMID- 15164394
TI  - Vibration exposure and disease in a shipyard: a 13-year revisit.
AB  - BACKGROUND: In a 1988 study of shipyard workers, a progressive association was
      observed between cumulative exposure to vibration and the vascular and
      neurological symptoms of the hand-arm vibration syndrome (HAVS). In 2001, after a
      decade of exposure reduction and ageing of the workforce, a second study at the
      same site was initiated. METHODS: In 2001, 214 subjects were selected; they
      represented four current weekly vibration exposure time intervals--0 hr, >0 < 5
      hr, > or =5 < 20 hr, > or =20 hr. The 1988 and 2000 cross-sectional populations
      were compared on the basis of exposure duration and current symptoms. RESULTS: In
      2001, the study population was 9.6 years older than the 1988 group. Current
      weekly exposure hours were similar in the low and medium exposure groups 2001 and
      1988, but exposure was reduced by an average of 9.7 hr per week in the highest
      exposure group (> or =20 hr) in 2001. Symptom severity was regressed
      polychotomously on estimated exposure (log cumulative hours); the OR was weaker
      in 2001 than in 1988 for sensorineural symptoms-1.44 [CI 1.04-1.98] versus 2.35
      [CI 1.48-3.73]. This was also true for vascular symptoms-1.70 [CI 1.06-2.71]
      versus 3.99 [CI 2.27-7.01]. Vascular symptoms were more prevalent in the highest
      lifetime vibration exposure group in 1988 (68.7 vs. 43.2% in 2001); sensorineural
      symptoms were more prevalent in the least vibration exposed group in 2001 (52.6
      vs. 20.7% in 1988). CONCLUSIONS: The prevalence of vascular symptoms associated
      with cumulative vibratory exposure was significantly greater in 1988, but
      neurological symptoms were more common at lower exposure levels in 2001. The
      presumption that reducing exposure duration alone is sufficient, in the absence
      of change in vibration magnitude, is not supported by the results of this study.

PMID- 15164395
TI  - Work-attributed symptom clusters (darkroom disease) among radiographers versus
      physiotherapists: associations between self-reported exposures and psychosocial
      stressors.
AB  - BACKGROUND: "Darkroom disease" (DRD) has been used to describe unexplained
      multiple symptoms attributed by radiographers to their work environment. This
      study determines the prevalence of symptom clusters similar to other unexplained
      syndromes among (medical radiation technologists (MRTs) as compared with
      physiotherapists (PTs), and identifies associated work-related (WR) factors.
      METHODS: A mail survey was undertaken of members of the professional associations
      of MRTs and PTs in Ontario, Canada. Questions were included to determine the
      prevalence and frequency of symptom clusters including abnormal tiredness as well
      as WR headaches, and symptoms suggestive of eye, nasal, and throat irritation.
      For the purpose of this study, these are considered to be DRD symptom clusters.
      Individuals with doctor-diagnosed asthma were excluded from our analyses.
      RESULTS: Overall, 63.9% of MRTs and 63.1% of PTs participated. Criteria for DRD
      were met by 7.8% of 1,483 MRTs and 1.8% of 1,545 PTs [odds ratio, OR 4.8
      (confidence interval, CI 3.1-7.5); (P < 0.0001)]. Both occupations showed
      significant associations between responses reflecting psychosocial stressors and
      DRD. Those with this symptom cluster were more likely to report additional
      symptoms than those without, and MRTs with DRD symptoms reported significantly
      more workplace chemical exposures. CONCLUSIONS: Findings suggest excess symptoms
      consistent with DRD among MRTs versus PTs, and there were associations among
      those meeting our definition of DRD with self-reported irritant exposures and
      psychosocial stressors.

PMID- 15164396
TI  - Neglecting safety precautions may lead to trenching fatalities.
AB  - BACKGROUND: Trench collapses ranked as the seventh leading cause of the possible
      twenty-nine causes of OSHA-inspected fatal construction events during the period
      1991-2001. This study aims to examine why these fatalities occurred. METHODS:
      Forty-four case files from OSHA inspections of fatal trench collapses were
      reviewed. RESULTS: Improper protection of the excavation site where work was
      taking place was the leading fatality cause. Several organizational or physical
      conditions were present at many fatal sites; the most frequent was that no
      training had been provided for trenching. CONCLUSIONS: Presence of a competent,
      diligent person at the site would have prohibited most fatalities. The top cited
      violation was lack of protection, that is, benching, shoring, sloping, trench
      boxes, etc. (29 CFR 1926.652 (a) (1)).

PMID- 15164397
TI  - An integrated comprehensive occupational surveillance system for health care
      workers.
AB  - BACKGROUND: Workers in the health care industry may be exposed to a variety of
      work-related stressors including infectious, chemical, and physical agents;
      ergonomic hazards; psychological hazards; and workplace violence. Many of these
      hazards lack surveillance systems to evaluate exposures and health outcomes. The
      development and implementation of a comprehensive surveillance system within the
      Duke University Health System (DUHS) that tracks occupational exposures and
      stressors as well as injuries and illnesses among a defined population of health
      care workers (HCWs) is presented. METHODS: Human resources job and work location
      data were used to define the DUHS population at risk. Outcomes and exposure data
      from existing occupational health and safety programs, health promotion programs,
      and employee health insurance claims, were linked with human resources data and
      de-identified to create the Duke Health and Safety Surveillance System (DHSSS).
      RESULTS: The surveillance system is described and four examples are presented
      demonstrating how the system has successfully been used to study consequences of
      work-related stress, hearing conservation program evaluation, risk factors for
      back pain and inflammation, and exposures to blood and body fluids (BBF).
      CONCLUSIONS: Utilization of existing data, often collected for other purposes,
      can be successfully integrated and used for occupational health surveillance
      monitoring of HCWs. Use of the DHSSS for etiologic studies, benchmarking, and
      intervention program evaluation are discussed.

PMID- 15164398
TI  - Surveillance of hazardous materials events in 17 states, 1993-2001: a report from
      the Hazardous Substances Emergency Events Surveillance (HSEES) system.
AB  - BACKGROUND: Thousands of acute hazardous materials (HazMat) releases occur
      annually throughout the United States. To prevent human exposure and resulting
      injuries, it is critical to understand the frequency with which these releases
      occur, the locations involved, the industries associated, and the specific
      substances being released. METHODS: HazMat events data from the Agency for Toxic
      Substances and Disease Registry's Hazardous Substances Emergency Events
      Surveillance (HSEES) system were analyzed for frequency and locations of
      occurrence, major industry categories and sub-categories involved, and substances
      released. The data analyzed were collected from 17 participating state health
      departments for 1993 through 2001. RESULTS: During 1993 through 2001, 53,142
      HazMat events occurred. Of the 17 states analyzed, Texas had the most releases,
      comprising 38.3% of all HSEES events. Of the 14 major US Census industry
      categories analyzed, the manufacturing category had the highest percentage of
      events (48.7%) followed by transportation, communication, and other public
      utilities (27.5%). Of the 10 states that participated during the entire analysis
      period, the numbers of events increased 64.3%. Twelve of 14 major industrial
      categories experienced increases in numbers of events over the analysis period,
      while public administration and active duty military events decreased. The
      substances released most frequently overall included ammonia, sulfur dioxide, and
      sulfuric acid, respectively. CONCLUSIONS: The HSEES data appear to reflect an
      upward trend in the occurrence of hazardous HazMat events. While it is difficult
      to definitively conclude whether this trend is due to more events actually
      occurring or from other factors, reviewing historical HazMat data may help
      communities, government agencies, and industries prevent or better prepare for
      potential events in the future.

PMID- 15164399
TI  - A disease and non-battle injury model based on Persian Gulf War admission rates.
AB  - BACKGROUND: Military planners must ensure adequate medical care for deployed
      troops-including care for disease and non-battle injuries (DNBI). This study
      develops a heuristic model with the three distinct phases of a warfighting
      operation (build-up, ground combat, post-combat) to assist in predicting DNBI
      incidence during warfighting deployments. METHODS: Inpatient healthcare records
      of soldiers deployed to the Persian Gulf War who were admitted with DNBI
      diagnoses were analyzed. DNBI admission rates for the three phases of the
      operation were examined and compared to rates for US Army Forces Command
      (FORSCOM) posts in the US. RESULTS: DNBI admission rates among the phases were
      distinctly different. The operation's overall rate and 95th percentile daily rate
      were less than the FORSCOM FY 1990 annual rate. CONCLUSIONS: The level of combat
      must be considered. The traditional use of average or overall rates should be
      abandoned when forecasting DNBI rates. Medical support projections should use
      separate 95th percentile DNBI admission rates for each of the phases.

PMID- 15164400
TI  - Trends in occupational lead exposure since the 1978 OSHA lead standard.
AB  - BACKGROUND: The purpose of the study was to evaluate trends in occupational lead
      exposures throughout U.S. industry after the establishment of the general
      industry lead standard in 1978 and the construction industry standard in 1993.
      METHODS: Lead exposure measurements collected by the Occupational Safety and
      Health Administration (OSHA) under their compliance and consultation programs
      were analyzed. Time trends in the distributions of exposure levels were evaluated
      graphically. Trends in the proportion of exposures above the OSHA permissible
      exposure limit (PEL) were analyzed using logistic regression models. RESULTS: The
      distribution of lead exposure levels declined over the study time period for
      general industry, but not for construction. The median exposure levels for
      general industry facilities decreased five- to tenfold. Logistic regression
      models reveal statistically significant declines in the odds of a lead exposure
      exceeding the PEL. CONCLUSIONS: This study provides evidence for relatively large
      decreases in lead exposure levels in general industry facilities over time. The
      study does not provide similar evidence for the construction industry. Given the
      limited number of years of data available since the implementation of the revised
      construction standard for lead, re-analysis of lead exposure levels within this
      industry would be worthwhile when more data become available.

PMID- 15164401
TI  - The doctors and the dockers.
AB  - BACKGROUND: London Dockers unloading a dusty asbestos cargo in 1965, consulted an
      eminent Occupational Health physician, Dr. Donald Hunter who informed them that
      they had been at serious risk. A second, opinion provided jointly by a Consultant
      Chest Physician, the Port Medical Officer, and the Medical Advisor to the Trades
      Union Congress, declared that they knew of no disease affecting dockers, and
      stated that intermittent exposure to asbestos constituted an inconsiderable risk
      that with certain precautions would be eradicated. METHODS: Archival material
      have been obtained to supplement limited published material and eyewitness
      accounts of the event, to provide a clearer picture of the issues. RESULTS:
      Reassured by the Chest Physician, the Port Medical Officer, and the Medical
      Advisor to the Trades Union Congress that they had little to fear, London dockers
      resumed unloading asbestos. From time to time dockers at other ports were to
      express concern and interrupt work, only to be similarly reassured. CONCLUSIONS:
      Had the medical troika in 1965 considered the available health statistics, they
      would have had reason to take a less sanguine attitude to the cancer mortality of
      dockers. An analysis of data for 16 selected occupations for the years 1900-1902,
      showed dockers to have an unhealthy job, with deaths from 'All Cancers' of 1.09
      per 1,000 years of life (the fourth highest). The Registrar General's
      occupational mortality report for 1951, noted excess tumors of the lung and
      stomach for dockers. Elevated Standardized Mortality Ratios for lung cancer had
      consistently been calculated by the Registrar General for the 20-64 age group of
      dockers; in 1931 (183), 1951 (149), and 1961 (169): by 1971 it would be 182. A
      total of 266 dockers were to be registered in the UK by 1999 as having died of
      malignant mesotheliomas, proving that Donald Hunter's concern for dockers had not
      been excessive.

PMID- 15164404
TI  - Fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal
      renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys.
AB  - OBJECTIVES: To evaluate fetal serum ss2-microglobulin and cystatin C in the
      prediction of post-natal renal function in bilateral hypoplasia and
      hyperechogenic enlarged kidneys. Predicting post-natal renal function is crucial
      to the prenatal evaluation of fetal nephropathies. Prenatal ultrasound can
      identify terminal renal failure, but is not sensitive enough to identify infants
      whose post-natal renal function will be impaired. Fetal serum ss2-microglobulin
      and cystatin C are potential predictors of post-natal renal function. METHODS:
      Fifty-four prenatally diagnosed cases of bilateral nephropathy were
      retrospectively reviewed. Final diagnosis was established using histological or
      post-natal findings: renal hypoplasia (n = 7), cystic dysplasia (n = 9),
      autosomal dominant polycystic kidney disease (ADPKD; n = 8) or autosomal
      recessive polycystic kidney disease (ARPKD; n = 22) and transient sonographic
      abnormalities (n = 8). Fetal serum ss2-microglobulin and cystatin C were assayed
      respectively in 54 and 38 cases. The prognostic value of these markers was
      assessed in terms of the post-natal outcome. RESULTS: In bilateral kidney
      hypoplasia and cystic dysplasia, ss2-microglobulin and cystatin C were
      significantly (p < 0.0001 and p < 0.02 respectively) higher than in the normal
      control group. In hyperechogenic fetal kidneys (ARPKD, ADPKD and transient
      sonographic abnormalities), these markers were not different from controls.
      However, whereas normal values cannot exclude renal failure, abnormal values
      predict post-natal renal failure. CONCLUSIONS: In bilateral renal hypoplasia and
      dysplasia, fetal serum ss2-microglobulin and cystatin C are good markers for post
      natal renal function. However, in bilateral renal hyperechogenic enlargement,
      abnormal values are associated with poor post-natal renal function, but normal
      values cannot preclude renal failure.

PMID- 15164405
TI  - Assessment of cortical gyrus and sulcus formation using magnetic resonance images
      in small-for-gestational-age fetuses.
AB  - OBJECTIVES: The purpose was to compare the development of gyrus and sulcus
      formation (GSF), an indicator of brain maturation, in small-for-gestational-age
      (SGA) fetuses using magnetic resonance (MR) imaging, with those of appropriate
      for-gestational-age (AGA) fetuses. METHODS: The 160 infants with a normal
      neurological outcome were divided into two groups on the basis of their body
      weight at delivery; 37 SGA infants (Group SGA) and 123 AGA infants (Group AGA).
      Fetal MR images, which were obtained from 28 to 39 gestational weeks in Group SGA
      and from 18 to 39 gestational weeks in Group AGA, were classified into the 8
      stages of development for GSF established by Abe et al. (2003), and comparison
      was made between the two groups retrospectively in their neurological development
      in relation to gestational age. RESULTS: In Group SGA, images were classified
      into stages 3 to 8 (P < 0.001). The gestational age of the cases determined for
      each stage between Groups SGA and AGA did not differ significantly, with respect
      to the development of GSF, despite differences in fetal estimated body weights.
      CONCLUSION: In SGA fetuses, evaluation of fetal GSF using MR images during the
      third trimester may be useful for predicting neurological prognoses postpartum.

PMID- 15164406
TI  - A comparative study of prenatal ultrasound findings and post-mortem examination
      in a tertiary referral centre.
AB  - This retrospective study compares the findings of prenatal ultrasound, performed
      in a tertiary fetal medicine centre, with the results of post-mortem examination
      in pregnancies complicated by suspected fetal abnormality that results in fetal
      loss. The study was carried out over a year at a teaching hospital, Fetal
      Medicine Centre and Regional Centre for Perinatal Pathology. Results were
      directly compared and the level of agreement between the ultrasound and post
      mortem findings described. These were classified as having complete agreement;
      major agreement or major disagreement. The group of cases with major agreement
      between findings was further divided into those with significant, or minor,
      additional findings at post-mortem examination. Over the 12-month period, 153
      ultrasound cases were identified, of which 47 were also examined by autopsy and
      were thus suitable for comparison in this study (30.7%). Complete agreement
      between ultrasound and post-mortem findings was found in 22 cases (46.8%). In 24
      cases (51.1%), major agreement between ultrasound and post-mortem findings was
      seen. Of these, 11 had minor additional findings at post-mortem examination and
      13 were found to have significant additional findings at post-mortem (27.7%),
      adding to the eventual diagnosis. In 12.8% of cases, post-mortem examination
      provided a definitive diagnosis. Only in one case was there complete discordance
      in the findings of the ultrasound examination and the autopsy (2.1%). No major
      disagreement between ultrasound and post-mortem findings was seen in 98% of
      cases. This study confirms the accuracy of prenatal ultrasound diagnosis in
      specialist centres, whilst emphasising the continuing importance of post-mortem
      examination in cases of fetal malformation to refine and, in some cases, define
      the diagnosis.

PMID- 15164407
TI  - A comparison of the impact of screen-positive results obtained from ultrasound
      and biochemical screening for Down syndrome in the first trimester: a pilot
      study.
AB  - OBJECTIVE: To compare the experiences of women who received a screen-positive
      test result for Down syndrome after nuchal translucency screening or after
      biochemical screening in the first trimester of pregnancy in the Netherlands.
      METHOD: Semi-quantitative questionnaires were sent to 40 women with a screen
      positive test result for Down syndrome in the first trimester of pregnancy: 20
      had undergone nuchal translucency screening (NT group) and 20 had undergone serum
      screening (PAPP-A and free beta-hCG) (SS group). In all the cases, chorionic
      villus sampling (CVS) had not revealed any chromosomal abnormalities. RESULTS:
      The major reason for undergoing the screening test in both groups of women was to
      be more reassured about the health of the baby. In the NT group, 5 out of the 20
      women stated that they had suddenly been confronted with the NT measurement
      during the ultrasound examination without even being asked, or had been caught by
      surprise about the possibility. Together with two other women, they felt that at
      that stage they had been insufficiently informed about what the test meant. In
      the SS group, two women also held this opinion. In 10 out of the 20 women in the
      SS group, the positive-screening result had caused (a great deal of) anxiety. In
      the NT group, this proportion was as high as 18 out of the 20. Six of the women
      in the NT group mentioned that 'seeing the baby' had been an important factor in
      their decision to undergo CVS. Even after a favourable result of CVS, a
      proportion of the pregnant women were still feeling anxious about the health of
      their baby (5 women in the SS group and 12 in the NT group). Nevertheless, a
      large proportion of the women in both groups was pleased that they had undergone
      the screening test. Only a few of them stated that they would not choose the same
      screening test again in a future pregnancy. CONCLUSIONS: An unfavourable
      screening result after NT screening appeared to have a greater impact than an
      unfavourable result after serum screening. This might partly be explained by the
      ultrasound examination visualising the increased risk during NT screening. An
      additional important role may have been played by the fact that an abnormal NT
      screening result implies an increased risk of other disorders besides Down
      syndrome, which the women should be informed about beforehand. Several factors
      place special demands on the counselling prior to NT screening.

PMID- 15164408
TI  - Semiquantitative assessment of myelination using magnetic resonance imaging in
      normal fetal brains.
AB  - OBJECTIVES: To evaluate the development of myelination in normal fetuses
      quantitatively using magnetic resonance (MR) imaging in relation to gestational
      age (GA). METHODS: Fetal MR images were obtained from 101 fetuses between 26 and
      39 weeks of gestation with no neurological problems. Regions of interest were
      designated in frontal lobe, corona radiata, optic radiation, thalamus, pons,
      cerebellar vermis, and vitreous body. The signal intensity ratio (SIR) was
      calculated by the signal intensity of each of these designated areas to that of
      the vitreous body and analyzed in relation to GA. RESULTS: The SIR of the frontal
      lobe did not vary significantly with GA. The SIR of the corona radiata and the
      optic radiation decreased significantly with GA (P < 0.05); after 34 weeks of
      gestation, they decreased sharply. The SIR of the thalamus, the pons, and the
      cerebellar vermis was significantly smaller than that of the cerebral white
      matter at 26 weeks of gestation (P < 0.05) and decreased significantly with GA (P
      < 0.05). CONCLUSION: Changes in the SIR approximately corresponded to the time
      course of progression of myelination in the previous histopathological reports.
      Semiquantitative evaluation on MR images may allow prenatal diagnosis of a delay
      or deficit of myelination.

PMID- 15164409
TI  - Identification of two mutations for ataxia telangiectasia among the Druze
      community.
AB  - Ataxia telangiectasia (AT) is a rare autosomal recessive disease characterized by
      progressive cerebellar ataxia, immunodeficiency, susceptibility to
      lymphoreticular malignancies and cancer predisposition, hypersensitivity to ionic
      radiation and chromosomal instability. In this study, we report a founder effect
      of AT with two different mutations: 1339 C > T and 6672 del GG together with 6677
      del TACG, found in four Israeli Druze clans originating from three different
      Druze centers in the Middle East (Lebanon, Syria and Jordan). The 1339 C > T
      mutation, which results in a stop codon at position 447 of the ATM protein, was
      observed in two unrelated clans originating from Lebanon and Jordan. The 6672 del
      GG/6677 del TACG mutation was observed in two unrelated clans originating from
      Syria and Lebanon. In the present study, simple and fast detection assays were
      developed for both mutations. The ability to identify AT carriers routinely
      provides a unique opportunity for prenatal diagnosis, genetic counseling as well
      as marriage guidance in the Druze community.

PMID- 15164410
TI  - Prenatal diagnosis of autosomal dominant hereditary spastic paraplegia (SPG4)
      using direct mutation detection.
AB  - OBJECTIVE: To present a report on prenatal diagnosis using direct SPG4 gene
      analysis in a family with autosomal dominant hereditary spastic paraplegia (AD
      HSP). METHODS: Genetic linkage and haplotype analysis were previously carried out
      with chromosome 2p markers. DNA was obtained from affected individuals, the
      affected father, the mother, and fetal DNA from an ongoing pregnancy by chorionic
      villus sampling (CVS) in the first trimester. The spastin gene (SPG4) was
      completely sequenced. RESULTS: A novel 832insGdelAA frameshift mutation,
      predicted to cause loss of functional protein, was identified in the affected
      father and in the fetal DNA. CONCLUSIONS: This is the first report on direct
      prenatal diagnosis of chromosome 2p-linked AD-HSP (SPG4). In addition, we report
      a novel SPG4-combined small insertion/deletion mutation in exon 5, which may be
      the first SPG4 mutational hot spot.

PMID- 15164411
TI  - Prenatal diagnosis of a fetus harboring an intermediate load of the A3243G mtDNA
      mutation in a maternal carrier diagnosed with MELAS syndrome.
AB  - We prenatally diagnosed MELAS syndrome in a fetus whose mother and older brother
      had the MELAS-specific A3243G mutation. The mutant mtDNA level of the amniotic
      fluid cells was not significantly different from that of the postnatal peripheral
      blood and hair follicle samples. The obstetrical course was uncomplicated except
      for transient exacerbation of the mother's diabetes, which required insulin
      control. At term, the infant was macrosomic, and the delivery was complicated by
      shoulder dystocia. MELAS syndrome in itself does not influence either the
      prenatal course of the mother or the fetal outcome. In contrast to the
      fulminating clinical course of this mother's first child, MELAS symptoms did not
      develop in her second child until age four, despite similar high tissue levels of
      mutant mtDNA. The phenotypic diversity in two offspring with similar higher
      levels of mutant mtDNA suggests that prenatal genetic diagnosis of cultured
      amniotic cells may yield results that are poor prognosticators of fetal outcome.

PMID- 15164412
TI  - Prenatal diagnosis of an isochromosome 5p in a fetus with increased nuchal
      translucency thickness and pulmonary atresia with hypoplastic right heart at 14
      weeks.
AB  - We report on a fetus presenting with increased nuchal translucency at 11 weeks'
      gestation, suggesting cystic hygroma. Chorion villous sampling was performed, and
      cytogenetic analysis revealed a supernumerary isochromosome 5p leading to
      tetrasomy 5p: 47,XX,+ i(5p)[7]/46,XX[5] after short-term culture and 47,XX,+
      i(5p)[20] after long-term culture. Subsequent targeted sonographic follow-up at
      12 and 14 weeks revealed further increase of the NT to 6.4 mm and the additional
      presence of a congenital heart defect (pulmonary atresia with intact ventricular
      septum). Termination of pregnancy was performed, and the heart defect was
      confirmed. Isochromosome 5p was found in varying proportions in all examined
      organs. Only a few cases of mosaic tetrasomy 5p have been reported in the
      literature, and recent reports on prenatally detected isochromosome 5p showed a
      possible relationship to increased nuchal translucency in some cases and also a
      possible role of confined mosaicism in others. Whereas cases with confined
      mosaicism did not show suspicious signs on ultrasound, true mosaicism conversely
      showed increased nuchal thickness as well as structural abnormalities. This is
      the first report on the association of a cardiac defect with this chromosome
      aberration.

PMID- 15164413
TI  - Another case of autosomal dominant exstrophy of the bladder.
AB  - OBJECTIVE: Exstrophy of the bladder is a rare malformation due to an anterior
      midline defect. Most cases of this condition with variable expression occur
      sporadically, but there are some cases indicative of a strong genetic component
      apart from environmental factors. This is a report about another rare mother
      child pair with bladder exstrophy. METHODS: We present the clinical data of a
      familial case of bladder exstrophy with an affected mother and her equally
      affected male fetus. RESULTS: Prenatal diagnosis of bladder exstrophy in the
      fetus was assessed by ultrasound at the 19th gestational week and was confirmed
      after termination of pregnancy at the 21st gestational week. CONCLUSION: The
      present case may be additional evidence for an autosomal dominant inherited
      variant of this malformation complex with implication for counselling of affected
      patients.

PMID- 15164414
TI  - Genetic approach to prenatal diagnosis in urea cycle defects.
AB  - OBJECTIVE: To demonstrate the feasibility of prenatal diagnosis by molecular
      genetics in all urea cycle defects in order to improve and standardize the
      current approaches. METHODS: Deceased index patients who had suffered from a urea
      cycle disorder were investigated for mutations of the biochemically most likely
      affected gene. If no material of index patients was available, parental DNA was
      studied for obligate carrier status. Fetal cells of 15 pregnancies, either
      chorionic villi or amniotic fluid cells, were used for direct sequence analysis
      of the respective mutations. Thirteen families were investigated, of which two
      were affected by N-acetylglutamate synthase deficiency, four by
      carbamoylphosphate synthetase 1 deficiency, one by ornithine transcarbamylase
      deficiency, three by argininosuccinate synthetase deficiency, two by
      argininosuccinate lyase deficiency, and one by arginase deficiency. RESULTS:
      Molecular genetics allowed the determination of the fetal status in all cases.
      Besides 14 known mutations, we detected the novel mutation c.544delC of the N
      acetylglutamate synthase gene, the novel missense mutation c.721G>A (E241K) of
      the argininosuccinate lyase gene, and the novel double mutated allele comprising
      the known mutation c.703G>A (G235R) and the novel insertion c.712ins[GGACC](2)
      (254X) of the arginase 1 gene. CONCLUSION: Direct genetic analysis of chorionic
      villi or amniotic fluid cells is feasible, fast, and specific, and can be
      regarded as the method of choice for prenatal diagnosis in urea cycle disorders.

PMID- 15164415
TI  - A novel PCR approach for prenatal detection of the common NEMO rearrangement in
      incontinentia pigmenti.
AB  - OBJECTIVES: Incontinentia pigmenti (IP) is a rare X-linked dominant
      genodermatosis that is usually lethal in males in the prenatal period. Largely
      80% of cases are accounted for by a large-scale deletion encompassing exons 4 to
      10 of the NEMO gene. The aim of this work was to facilitate prenatal diagnosis of
      IP by devising a novel test for detection of the prevalent NEMO deletion.
      METHODS: We devised a sensitive and reproducible multiplex PCR test enabling
      simultaneous amplification of the deleted and wild-type NEMO genes in IP female
      individuals. RESULTS: Combination of this DNA test, with Xq28 linkage analysis
      and X-inactivation pattern study enabled us to offer an IP prenatal diagnosis in
      15 of the 16 couples at a 50% risk to have an affected offspring. CONCLUSION: A
      current approach to IP prenatal diagnosis is proposed on the basis of the
      previously mentioned molecular tools.

PMID- 15164416
TI  - Prenatal screening for Down syndrome: the problem of recurrent false-positives.
AB  - OBJECTIVES: It has been reported that, in prenatal screening programmes for Down
      syndrome, women who have false-positive results in one pregnancy have an
      increased risk of a false-positive result in a subsequent pregnancy. We examined
      the effect of this in the screening programme conducted from the Wolfson
      Institute of Preventive Medicine with a view to determining the magnitude of the
      effect, and to describe a method of avoiding the problem. METHODS: Six thousand
      four hundred and forty-eight women were identified who had had two singleton
      pregnancies without Down syndrome in the screening programme based at the Wolfson
      Institute of Preventive Medicine, in which both pregnancies were screened using a
      Quadruple test (maternal age with alphafetoprotein (AFP), unconjugated oestriol
      (uE(3)), total or free beta-human chorionic gonadotrophin (hCG) and either free
      alpha-hCG or inhibin-A as the fourth serum marker). RESULTS: Among women who had
      a false-positive result in their initial pregnancy, the false-positive rate in
      the subsequent pregnancy was high: 20% (46/229), about three times higher than
      both the overall observed false-positive rate (6.6%), and the expected false
      positive rate, in subsequent pregnancies that were false-positive in their
      initial pregnancy (7.5%) (p < 0.001). This arises because serum marker levels in
      one pregnancy are associated with the levels in a subsequent pregnancy. Using the
      slope (the regression coefficient b) of each marker level in a subsequent
      pregnancy regressed on the value in the first pregnancy, it is possible to adjust
      all marker values in a subsequent pregnancy to allow for the higher-than-expected
      false-positive rate. This can be done by dividing the observed MoM value for each
      marker by the 'expected' MoM, which is the MoM value in a previous pregnancy
      raised to the power b. CONCLUSIONS: If a woman has had a false-positive result in
      one pregnancy, she is much more likely to have a false-positive screening result
      in a subsequent pregnancy than women in general. The problem can be avoided by
      adjusting the serum markers in all women who have been screened in a previous
      pregnancy and who have not had a previous pregnancy with Down syndrome.

PMID- 15164417
TI  - Prenatal overgrowth and mosaic trisomy 15q25-qter including the IGF1 receptor
      gene.
AB  - Overgrowth is rarely associated with chromosomal imbalances. Here, we report on a
      male foetus presenting with overgrowth and additional material on the short arm
      of one of the chromosome 15 in 12% of lymphocytes and 50% of amniotic cells.
      Parents' karyotypes were normal, indicating a de novo origin for this unbalanced
      rearrangement. Complementary studies using cytogenetic and FISH studies showed
      that this additional material resulted in a 15q25-qter trisomy and confirmed the
      presence of three copies of the insulin-like growth factor 1 receptor (IGF1R)
      gene, included in the trisomic region. Autopsy performed after termination of
      pregnancy revealed isolated overgrowth and absence of visceral malformations. The
      possible mechanisms and origins for the formation of this mosaic pure trisomy are
      complex. The present observation emphasises the hypothesis that the overgrowth
      phenotype, frequently reported in patients with trisomy including the 15q26
      region, might be causally related to a dosage effect of the IGF1R gene, as well
      as the importance of chromosome analysis in patients with overgrowth. It also
      confirms that the overgrowth is of prenatal onset in those observations.

PMID- 15164418
TI  - Prenatal identification of fetal overgrowth, abdominal wall defect, and neural
      tube defect in pregnancies achieved by assisted reproductive technology.

PMID- 15164419
TI  - Nucleotide differences in SMN1 and SMN2 gene.

PMID- 15164420
TI  - Second-trimester nasal bone hypoplasia/aplasia associated with cleidocranial
      dysplasia.

PMID- 15164421
TI  - Late granule cell genesis in quail cerebellum.
AB  - Proliferation of avian cerebellar neurons, including granule cells, is thought to
      be completed during embryonic life, and aspects of cell addition in cerebellar
      lobules in posthatching life are unknown. The present study tested the hypothesis
      that cell genesis in late embryonic and posthatching stages of quail cerebellum
      occurs in parallel with the performance of motor programs. After exposure to
      bromodeoxyuridine, short (20 hours) and long survival time points were selected
      to investigate survival and migration of labeled cells. Quantitative analysis of
      the lobular distribution of labeled cells was performed with the stereological
      disector method. External granular layer (EGL) proliferation did not cease after
      hatching, indicating that there is an extended posthatching period, lasting until
      P20, when cells can be added into the internal granular layer, modifying the
      cerebellar circuitry and function. Indeed, long survival experiments suggested
      that EGL-labeled cells migrated into the internal granular layer and survived for
      a prolonged time, although many of the progenitor cells remained in the EGL for
      days. Double-labeling experiments revealed that most of the late-generated
      granule cells were NeuN positive, but only few expressed nitric oxide synthase.
      In addition to granule cells, the white matter and a glutamic acid decarboxylase
      (GAD)-positive cell population in the molecular layer around Purkinje somata
      showed bromodeoxyuridine labeling. Although all lobules showed significant
      posthatching proliferation, an anteroposterior gradient was evident. The index of
      granule cell production and survival supports a spatiotemporal pattern, in
      correlation with the functional division of cerebellum into anterior and
      posterior domains.

PMID- 15164422
TI  - Cerebral areas mediating visual redirection of gaze: cooling deactivation of 15
      loci in the cat.
AB  - In humans, damage to posterior parietal or frontal cortices often induces a
      severe impairment of the ability to redirect gaze to visual targets introduced
      into the contralateral field. In cats, unilateral deactivation of the posterior
      middle suprasylvian (pMS) sulcus in the posterior inferior parietal region also
      results in an equally severe impairment of visually mediated redirection of gaze.
      In this study we tested the contributions of the pMS cortex and 14 other cortical
      regions in mediating redirection of gaze to visual targets in 31 adult cats.
      Unilateral cooling deactivation of three adjacent regions along the posterior
      bend of the suprasylvian sulcus (posterior middle suprasylvian sulcus, posterior
      suprasylvian sulcus, and dorsal posterior ectosylvian gyrus at the confluence of
      the occipital, parietal, and temporal cortices) eliminated visually mediated
      redirection of gaze towards stimuli introduced into the contralateral hemifield,
      while the redirection of gaze toward the ipsilateral hemifield remained highly
      proficient. Additional cortical loci critical for visually mediated redirection
      of gaze include the anterior suprasylvian gyrus (lateral area 5, anterior
      inferior parietal cortex) and medial area 6 in the frontal region. Cooling
      deactivation of: 1) dorsal or 2) ventral posterior suprasylvian gyrus; 3) ventral
      posterior ectosylvian gyrus, 4) middle ectosylvian gyrus; 5) anterior or 6)
      posterior middle suprasylvian gyrus (area 7); 7) anterior middle suprasylvian
      sulcus; 8) medial area 5; 9) the visual portion of the anterior ectosylvian
      sulcus (AES); 10) or lateral area 6 were all without impact on the ability to
      redirect gaze. In summary, we identified a prominent field of cortex at the
      junction of the temporo-occipito-parietal cortices (regions pMS, dPE, PS), an
      anterior inferior parietal field (region 5L), and a frontal field (region 6M)
      that all contribute critically to the ability to redirect gaze to novel stimuli
      introduced into the visual field during fixation. These loci have several
      features in common with cortical fields in monkey and human brains that
      contribute to the visually guided redirection of the head and eyes.

PMID- 15164423
TI  - Fiber connections of the lateral valvular nucleus in a percomorph teleost,
      tilapia (Oreochromis niloticus).
AB  - Fiber connections of the lateral valvular nucleus were investigated in a
      percomorph teleost, the tilapia (Oreochromis niloticus), by tract-tracing
      methods. Following tracer injections into the lateral valvular nucleus, neurons
      were labeled in the ipsilateral dorsal part of dorsal telencephalic area, corpus
      glomerulosum pars anterior, dorsomedial thalamic nucleus, central nucleus of the
      inferior lobe, mammillary body, semicircular torus, valvular and cerebellar
      corpus, in the bilateral rostral regions of the central part of dorsal
      telencephalic area, dorsal region of the medial part of dorsal telencephalic
      area, habenula, anterior tuberal nucleus, posterior tuberal nucleus, and spinal
      cord, and in the contralateral lateral funicular nucleus. Labeled fibers and
      terminals were found in the ipsilateral cerebellar corpus and bilateral valvula
      of the cerebellum. Tracers were injected into portions of the telencephalon,
      pretectum, inferior lobe, and cerebellum to confirm reciprocally connections with
      the lateral valvular nucleus and to determine afferent terminal morphology in the
      lateral valvular nucleus. Telencephalic fibers terminated mainly in a
      dorsolateral portion of the lateral valvular nucleus. Terminals from the corpus
      glomerulosum pars anterior, central nucleus of the inferior lobe, and mammillary
      body showed more diffuse distributions and were not confined to particular
      portions of the lateral valvular nucleus. Labeled terminals in the lateral
      valvular nucleus were cup-shaped or of beaded morphology. These results indicate
      that the lateral valvular nucleus receives projections from various sources
      including the telencephalon, pretectum, and inferior lobe to relay information to
      the valvular and cerebellar corpus. In addition, the corpus glomerulosum pars
      anterior in tilapia is considered to be homologous to the magnocellular part of
      superficial pretectal nucleus in cyprinids.

PMID- 15164424
TI  - Intergeniculate leaflet and ventral lateral geniculate nucleus afferent
      connections: An anatomical substrate for functional input from the vestibulo
      visuomotor system.
AB  - The intergeniculate leaflet (IGL) has widespread projections to the basal
      forebrain and visual midbrain, including the suprachiasmatic nucleus (SCN). Here
      we describe IGL-afferent connections with cells in the ventral midbrain and
      hindbrain. Cholera toxin B subunit (CTB) injected into the IGL retrogradely
      labels neurons in a set of brain nuclei most of which are known to influence
      visuomotor function. These include the retinorecipient medial, lateral and dorsal
      terminal nuclei, the nucleus of Darkschewitsch, the oculomotor central gray, the
      cuneiform, and the lateral dorsal, pedunculopontine, and subpeduncular pontine
      tegmental nuclei. Intraocular CTB labeled a retinal terminal field in the medial
      terminal nucleus that extends dorsally into the pararubral nucleus, a location
      also containing cells projecting to the IGL. Distinct clusters of IGL-afferent
      neurons are also located in the medial vestibular nucleus. Vestibular projections
      to the IGL were confirmed by using anterograde tracer injection into the medial
      vestibular nucleus. Other IGL-afferent neurons are evident in Barrington's
      nucleus, the dorsal raphe, locus coeruleus, and retrorubral nucleus. Injection of
      a retrograde, trans-synaptic, viral tracer into the SCN demonstrated transport to
      cells as far caudal as the vestibular system and, when combined with IGL
      injection of CTB, confirmed that some in the medial vestibular nucleus
      polysynaptically project to the SCN and monosynaptically to the IGL, as do cells
      in other brain regions. The results suggest that the IGL may be part of the
      circuitry governing visuomotor activity and further indicate that circadian
      rhythmicity might be influenced by head motion or visual stimuli that affect the
      vestibular system.

PMID- 15164425
TI  - Characterization of long-term mouse brain aggregating cultures: evidence for
      maintenance of neural precursor cells.
AB  - An extensive characterization of fetal mouse brain cell aggregates has been
      performed using immunohistochemical and stereological methods. Single cell
      suspensions from mechanically dissociated cortex and hippocampus were cultured in
      serum-free, B27-supplemented medium under constant gyratory agitation for up to
      56 days. Three-dimensional aggregates started to form immediately after seeding
      and reached a final average size of 500 microm in diameter. Among the cell types
      identified, neurons were the most abundant cells in the aggregates, followed by
      astrocytes, microglia, and oligodendrocytes. Western blotting for synaptophysin
      and immunostaining for neurotransmitter-related molecules indicated the presence
      of well-defined phenotypic characteristics of the neurons in this culture system,
      suggesting functionality. Proliferating cells, many with neural precursor cell
      properties, were seen throughout the culture period and could be isolated from
      the aggregates even after 2 months in culture. Neural precursor cells were
      isolated from the aggregates after more than 1 month in culture; these cells were
      successfully differentiated into neurons, astrocytes, and oligodendrocytes. The
      aggregate culture system may provide a versatile tool for molecular dissection of
      processes identified in mouse models, including transgenic animals and
      manipulation of neural precursor cells.

PMID- 15164427
TI  - Wnt genes define distinct boundaries in the developing human brain: implications
      for human forebrain patterning.
AB  - Understanding the factors that govern human forebrain regionalization along the
      dorsal-ventral and left-right (L-R) axes is likely to be relevant to a wide
      variety of neurodevelopmental and neuropsychiatric conditions. Recent work in
      lower vertebrates has identified several critical signaling molecules involved in
      embryonic patterning along these axes. Among these are the Wingless-Int (WNT)
      proteins, involved in the formation of dorsal central nervous system (CNS)
      structures, as well as in visceral L-R asymmetry. We examined the expression of
      WNT2b and WNT7b in the human brain, because these genes have highly distinctive
      expression patterns in the embryonic mouse forebrain. In the human fetal
      telencephalon, WNT2b expression appears to define the cortical hem, a dorsal
      signaling center previously characterized in mouse, which is also confirmed by
      BMP7 expression. In diencephalon, WNT2b expression is restricted to medial dorsal
      structures, including the developing pineal gland and habenular nucleus, both
      implicated in CNS L-R asymmetry in lower organisms. At 5 weeks gestation, WNT7b
      is expressed in cerebral cortical and diencephalic progenitor cells. As the
      cortical plate develops, WNT7b expression shifts, demarcating deep layer neurons
      of the neocortex and the hippocampal formation. Spatial and temporal expression
      patterns show startling similarity between human and mouse, suggesting that the
      developmental roles of these WNT genes may be highly conserved, despite the far
      greater size and complexity of the human forebrain.

PMID- 15164426
TI  - Paucity of horizontal connections for binocular vision in V1 of naturally
      strabismic macaques: Cytochrome oxidase compartment specificity.
AB  - To describe the structural basis for lack of binocular fusion in strabismic
      primates, we investigated intrinsic horizontal connections within striate cortex
      (area V1) of normal and strabismic, adult macaque monkeys. The strabismic animals
      had early-onset natural esotropia (the visual axes deviated nasally), normal
      visual acuity in each eye, and the constellation of ocular motor deficits that
      typify human infantile strabismus. Horizontal patchy connections and synaptic
      boutons were labeled by injections of the neuronal tracer biotinylated dextran
      amine. Ocular dominance columns (ODCs), and blob vs. interblob compartments, were
      revealed by using cytochrome oxidase (CO). In layers 2/3 and 4B of the strabismic
      monkeys, patchy projections and boutons terminated much more frequently in same
      eye (73%) as opposed to opposite-eye (27%) ODCs (normal monkeys 58% and 42%,
      respectively). The deficiency of binocular connections in the strabismic cortex
      was evident qualitatively as a "skip" pattern, in which every other row of ODCs
      had labeled patches. Analysis of V1 in normal monkeys revealed that the deficits
      in strabismic V1 were due mainly to a loss of binocular connections between
      neurons in CO-interblob compartments. In both normal and strabismic monkeys: (1)
      CO-blob compartment neurons showed a more pronounced bias for monocular
      connectivity, and (2) commitment of connections to the same CO-compartment as the
      injection site (blob-to-blob, or interblob-to-interblob) was moderately strong
      (64%) but far from absolute. These findings help elucidate the relative roles of
      visual experience vs. innate mechanisms in the development of axonal connections
      between ocular dominance domains and compartments within macaque V1. They also
      provide the first detailed description of the V1 maldevelopments associated with
      unrepaired natural, infantile-onset strabismus in primates.

PMID- 15164428
TI  - Cytoarchitectonic characterization of the parahippocampal region of the guinea
      pig.
AB  - The cytoarchitectonic features of the parahippocampal region (PHR) in the guinea
      pig are described, based on coronal, horizontal, and sagittal 50-microm sections
      stained for Nissl substance, zinc, parvalbumin, or calbindin. We differentiate
      between perirhinal (PRC), postrhinal (POR), and entorhinal (ERC) cortices. PRC is
      divided into areas 35 and 36 occupying the fundus and the dorsal bank of the
      rhinal fissure, respectively. POR is located caudal to the PRC. POR and area 36
      show a dense, clustered cellular layer II and a thinner layer III in comparison
      to the adjacent neocortex, and they differ from each other with respect to the
      orientation of the somata of layer VI neurons. Area 35 is characterized by a thin
      layer II that is not very different from layer III. Layer IV is (dys)granular in
      area 36 and POR, and is absent in area 35 and ERC. ERC, located ventromedial to
      the PRC and POR, is subdivided in six fields, of which field 5 is adjacent to
      area 35. In both area 35 and field 5, no clear differentiation between layers II
      and III is present. Field 5 shows a darker cellular stain and exhibits a cell
      free zone or lamina dissecans between layers III and V. Medial to field 5, an
      area characterized by large cell clusters in layer II is designated field 4. The
      latter field is replaced by field 3 rostromedially, which also typically shows
      clustering of layer II neurons. These cell clusters in field 3, however, are much
      more constant in size in spacing compared to those in field 4. The caudomedial
      portion of ERC is subdivided into fields 1, 1', and 2. The latter, characterized
      by a homogeneous distribution of neurons in all layers with large darkly stained
      neurons in layer V is positioned rostral to field 1 and caudomedial to fields 4
      and 5. In field 1, layers V and VI are thinner, and layer II neurons are smaller
      then in field 1' and field 2. We conclude that the architectonic features of the
      guinea pig PHR are comparable to those described in other mammals, particularly
      the rat.

PMID- 15164429
TI  - Timing and topography of cell genesis in the rat retina.
AB  - To understand the mechanisms of cell fate determination in the vertebrate retina,
      the time course of the generation of the major cell types needs to be
      established. This will help define and interpret patterns of gene expression,
      waves of differentiation, timing and extent of competence, and many of the other
      developmental processes involved in fate acquisition. A thorough retinal cell
      "birthdating" study has not been performed for the laboratory rat, even though it
      is the species of choice for many contemporary developmental studies of the
      vertebrate retina. We investigated the timing and spatial pattern of cell genesis
      using 3H-thymidine (3H-TdR). A single injection of 3H-TdR was administered to
      pregnant rats or rat pups between embryonic day (E) 8 and postnatal day (P) 13.
      The offspring of prenatally injected rats were delivered and all animals survived
      to maturity. Labeled cells were visualized by autoradiography of retinal
      sections. Rat retinal cell genesis commenced around E10, 50% of cells were born
      by approximately P1, and retinogenesis was complete near P12. The first
      postmitotic cells were found in the retinal ganglion cell layer and were 9-15
      microm in diameter. This range includes small to medium diameter retinal ganglion
      cells and large displaced amacrine cells. The sequence of cell genesis was
      established by determining the age at which 5, 50, and 95% of the total
      population of cells of each phenotype became postmitotic. With few exceptions,
      the cell types reached these developmental landmarks in the following order:
      retinal ganglion cells, horizontal cells, cones, amacrine cells, rods, bipolar
      cells, and Muller glia. For each type, the first cells generated were located in
      the central retina and the last cells in the peripheral retina. Within the
      sequence of cell genesis, two or three phases could be detected based on
      differences in timing, kinetics, and topographic gradients of cell production.
      Our results show that retinal cells in the rat are generated in a sequence
      similar to that of the primate retina, in which retinogenesis spans more than 100
      days. To the extent that sequences reflect underlying mechanisms of cell fate
      determination, they appear to be conserved.

PMID- 15164430
TI  - Safety in numbers.

PMID- 15164431
TI  - Improving the outcome for older women with breast cancer.

PMID- 15164432
TI  - Evolution of surgical treatment for pharyngeal pouch.
AB  - BACKGROUND: The development of endoscopic techniques, particularly endoscopic
      stapling, has led to a re-evaluation of the treatment of pharyngeal pouch. The
      pathophysiology and treatment of the condition is reviewed. METHODS: An
      electronic literature search was undertaken on the pathophysiology, history and
      surgery of pharyngeal pouch (Zenker's diverticulum). These last two terms were
      used to the search the Cochrane, Medline and Embase databases (from 1966 to date)
      and the bibliographies of extracted articles. RESULTS AND CONCLUSION: With
      recognition of the central role of the cricopharyngeus muscle in the pathogenesis
      of pouch formation, the emphasis on treatment has shifted from diverticulectomy
      to cricopharyngeal myotomy. Minimally invasive techniques have become established
      since the advent of endoscopic stapling devices. Although randomized controlled
      data are lacking, the endoscopic approach appears to offer advantages in terms of
      a shorter duration of anaesthesia, more rapid resumption of oral intake, shorter
      hospital stay and quicker recovery. It is associated with excellent success rates
      and minimal morbidity.

PMID- 15164433
TI  - Systematic review of safety and effectiveness of an artificial bowel sphincter
      for faecal incontinence.
AB  - BACKGROUND: The aim was to determine the safety and effectiveness of the
      implantation of an artificial bowel sphincter for the treatment of severe faecal
      incontinence. METHOD: Medical bibliographic databases, the internet and reference
      lists were searched from January 1966 to January 2003. Only the lowest level of
      evidence was available for inclusion in this systematic review. Case series and
      case reports were selected to assess safety, whereas only case series were
      selected to assess effectiveness. RESULTS: Fourteen studies met the inclusion
      criteria. A number of safety issues were reported, including high explantation
      rates, and rates of adverse events owing to infection, device malfunction,
      ulceration and pain. Results in published reports were not analysed on an
      intention-to-treat basis. Continence, quality of life and manometry scores were
      reported for patients with a functioning device at the end of follow-up. These
      patients experienced a significant improvement in their level of continence. As
      no outcome data were presented for those with a non-functioning or explanted
      device, it is possible that such patients may have a worsened degree of
      incontinence or decreased quality of life. CONCLUSION: Implantation of an
      artificial bowel sphincter is of uncertain benefit and may possibly harm many
      patients. Patient selection is therefore critical and should be enhanced by
      higher-quality research.

PMID- 15164434
TI  - Management of in-transit metastases from cutaneous malignant melanoma.
AB  - BACKGROUND: In-transit metastases from cutaneous malignant melanoma (cutaneous or
      subcutaneous deposits between the primary melanoma and regional lymph nodes)
      represent late-stage disease, and their treatment should be tailored accordingly.
      This article reviews the pathology, clinical significance and treatment options
      for in-transit disease from melanoma. METHODS: An initial Medline search was
      undertaken using the keywords 'melanoma and in-transit' and 'melanoma and non
      nodal regional recurrence'. Additional original articles were obtained from
      citations in articles identified by the initial search. RESULTS AND CONCLUSION:
      In-transit metastases carry a poor prognosis. The method of treatment should be
      tailored to the extent of cutaneous disease. The first line of treatment remains
      complete excision with negative histopathological margins. There is no need for
      wide excision. Carbon dioxide laser therapy is valuable for multiple small
      cutaneous deposits. Isolated limb perfusion has a role for numerous or bulky
      advanced in-transit metastases in the limbs that are beyond the scope of simpler
      techniques. Systemic chemotherapy has response rates of about 25 per cent and is
      reserved for patients for whom surgery is no longer feasible.

PMID- 15164435
TI  - Early postoperative small bowel obstruction.
AB  - BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is a distinct
      clinical entity that is often difficult to differentiate from postoperative
      ileus. METHODS: A literature search was performed for articles dealing with early
      postoperative small bowel obstruction using Medline and Google. RESULTS AND
      CONCLUSION: When bowel function does not return within 5 days after surgery,
      causes of persistent ileus should be excluded and treated. Most instances of
      mechanical EPSBO can be treated expectantly for at least 10-14 days with almost
      no risk of bowel strangulation. Some causes of obstruction (for example
      herniation at a laparoscopic trocar site) require early reintervention, whereas
      in other cases (such as radiation enteritis, carcinomatosis) reintervention may
      be deferred indefinitely. Many episodes of EPSBO resolve without the cause being
      elucidated.

PMID- 15164436
TI  - Randomized clinical trial to assess the effect of an educational programme
      designed to improve nurses' assessment and recording of postoperative pain.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of an intervention
      designed to improve postoperative pain assessment and recording by nurses.
      METHODS: This cluster randomized clinical trial included two intervals of 3
      months each: a preintervention observational study (period 1) followed by a
      period of intervention (period 2). Six surgical wards were randomly assigned to
      receive either an experimental intervention, including educational seminars for
      nurses on pain, pain assessment and the use of a visual analogue scale (n = 3),
      or standard care (control group; n = 3). The main outcome measures were the
      percentage of patients in whom pain was assessed, number of pain assessments per
      patient and postoperative pain intensity scores. RESULTS: A total of 2278
      patients were included. Significant improvements were found in the percentage of
      patients in whom pain was assessed and the number of daily pain assessments per
      patient in the intervention group between periods 1 and 2. In contrast, these
      outcomes were unchanged between the two intervals in wards randomized to standard
      care. During period 2, pain scores at 48 h were significantly decreased in the
      intervention wards compared with those in the control group. CONCLUSION: An
      educational programme dedicated to nurses strongly increased the use of regular
      pain assessment, and may have contributed to a modest improvement in
      postoperative analgesia.

PMID- 15164438
TI  - Use of donor aorta for arterial reconstruction in paediatric liver and
      multivisceral transplantation.
AB  - BACKGROUND: Arterial reconstruction remains the most important technical issue in
      paediatric transplantation. The arteries of paediatric donors as well as
      recipients are small and friable. The aim of this study was to assess the use of
      the donor aorta as a conduit for arterial reconstruction in paediatric liver and
      multivisceral transplantation. METHODS: Between June 1994 and January 2002, 284
      paediatric transplants, including 197 cadaveric liver and multivisceral
      transplants, were performed in children at this centre. Of these, 41 (20.8 per
      cent), including nine cadaveric liver transplants and 32 multivisceral
      transplants, were revascularized by donor aortic reconstruction. Patient
      demographics, types of donor arterial reconstruction, technical complications and
      incidence of hepatic artery thrombosis were reviewed. RESULTS: None of the 41
      donor aortic reconstructions used in revascularization of paediatric liver and
      multivisceral transplants thrombosed. There were no bleeding complications and no
      pseudoaneurysms developed. CONCLUSION: Arterial reconstruction using donor aorta
      is a useful option with a low incidence of thrombosis in paediatric
      transplantation.

PMID- 15164437
TI  - Late follow-up of a randomized trial of surgery plus tamoxifen versus tamoxifen
      alone in women aged over 70 years with operable breast cancer.
AB  - BACKGROUND: Breast cancer has been considered a more indolent disease in the
      elderly, who are less tolerant of aggressive therapy. This trial tested the
      hypothesis that tamoxifen without surgery would provide adequate control of
      breast cancer for the remainder of life in elderly women, thereby sparing them
      surgery. METHOD: Women aged over 70 years with operable, invasive breast cancer
      were randomized to receive either tamoxifen alone or surgery plus tamoxifen. Time
      to treatment failure (TTF), indicating initial primary treatment failure, was the
      primary endpoint. Overall mortality, and death from breast cancer were also
      compared between the two groups. RESULTS: Between 1984 and 1991, 455 patients
      were included in the trial. The analysis was based on a median follow-up of 12.7
      years. The TTF was significantly shorter in the tamoxifen alone group: hazard
      ratio (HR) 4.41 (95 per cent confidence interval (c.i.) 3.31 to 5.88). Ninety
      three (40.4 per cent) of 230 patients randomized to tamoxifen alone underwent
      surgery for the management of their disease. Both overall mortality and mortality
      from breast cancer were significantly increased in the tamoxifen alone group,
      although the survival curves did not diverge for the first 3 three years: HR 1.29
      (95 per cent c.i. 1.04 to 1.59) and 1.68 (95 per cent c.i. 1.15 to 2.47)
      respectively. CONCLUSION: Omission of primary surgery in unselected elderly women
      with operable breast cancer who were fit for the procedure resulted in an
      increased rate of progression, therapeutic intervention and mortality.

PMID- 15164439
TI  - Prediction of mediastinal lymph node metastasis in medullary thyroid carcinoma.
AB  - BACKGROUND: Mediastinal lymph node metastases can be life threatening owing to
      their proximity to vital organs. Reliable identification of mediastinal
      metastasis is of utmost importance for timely mediastinal lymph node dissection,
      although suitable clinicopathological variables for their detection in patients
      with thyroid cancer have yet to be identified. METHODS: This was an analysis of
      83 consecutive patients with radiological suspicion of mediastinal metastasis who
      underwent trans-sternal mediastinal lymph node dissection for node-positive
      medullary thyroid carcinoma between November 1994 and March 2003. RESULTS:
      Univariate analysis revealed that extrathyroidal extension (P < 0.001), distant
      metastasis (P = 0.001), the preoperative serum calcitonin level (P = 0.001),
      operation type (P = 0.004), contralateral cervicolateral metastasis (P = 0.016)
      and bilateral nodal metastasis (P = 0.031) were significantly associated with
      mediastinal involvement. Only extrathyroidal extension remained significant in a
      multivariate logistic regression analysis of mediastinal lymph node metastasis.
      Prediction of mediastinal metastasis by extrathyroidal extension was best at
      reoperation, with a specificity of 97 per cent and a positive predictive value of
      88 per cent. CONCLUSION: Mediastinal lymph node dissection should be considered
      in patients undergoing reoperation for node-positive medullary thyroid carcinoma
      who have extrathyroidal extension and cervical lymph node metastases.

PMID- 15164440
TI  - Phenotypic expression of a family with multiple endocrine neoplasia type 2A due
      to a RET mutation at codon 618.
AB  - BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense
      mutations in the RET proto-oncogene on chromosome 10. This paper reports the
      phenotypic expression of a family with MEN2A, in which serine substitutes for
      cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that
      medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this
      has recently been updated to intermediate-high risk, based on stratified genetic
      information. METHODS: The family was mapped over six generations. In 1971 family
      members were invited to join a screening programme. Genetic testing was started
      in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the
      screening programme. One screened patient had a phaeochromocytoma and four had
      hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases
      and two young patients also had liver metastases. No screened patient died from
      MTC during a mean observation time of 19 years. Six other family members were
      diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION:
      Because of the great interindividual differences in tumour aggressiveness within
      the family it is impossible to predict whether an individual gene carrier will
      have an aggressive MTC or not. This unpredictability is an additional argument,
      besides those obtained in stratified genetic studies, for operating on gene
      carriers at young age.

PMID- 15164441
TI  - Assessment of satisfaction with care after inpatient treatment for oesophageal
      and gastric cancer.
AB  - BACKGROUND: Patients' views are becoming increasingly important in the current
      health system. They provide information on effectiveness of healthcare and how it
      may be improved. This study aimed to measure patients' satisfaction with care
      received for treatment of oesophageal and gastric cancer, and to identify areas
      that contribute most to overall satisfaction scores. METHODS: Consecutive
      inpatients with oesophageal and gastric cancer treated in one surgical unit were
      recruited prospectively during a 2-year period. The European Organization for
      Research and Treatment of Cancer 'satisfaction with in-hospital care'
      questionnaire (QLQ-SAT32) was completed following discharge. Scores ranged from 0
      to 100 for each satisfaction scale. Univariable and multivariable analysis was
      used to define the relationships between the different dimensions of satisfaction
      with care and the overall score. RESULTS: Ninety-one patients (mean age 67 years,
      60 men) completed the questionnaire a mean of 40 days after treatment. The
      highest scores were for doctors (mean 72), nurses (mean 67) and overall
      satisfaction (mean 68). Univariable analysis showed that all dimensions of
      satisfaction with care contributed significantly to overall satisfaction (P <
      0.001). Multivariable analyses, however, showed that most of the variation in
      overall satisfaction could be attributed to levels of satisfaction with doctors,
      nurses, and hospital comfort and cleanliness. CONCLUSION: Satisfaction with care
      in these surgical patients was high and could be measured using a
      multidimensional instrument. Overall satisfaction was not influenced equally by
      all aspects of care. The strongest contributors to overall satisfaction in this
      study were doctors, nurses and hospital cleanliness.

PMID- 15164442
TI  - Comparison of three different procedures for antireflux surgery.
AB  - BACKGROUND: No long-term comparisons of the various open and laparoscopic
      antireflux procedures have been undertaken. The aim of this study was to compare
      symptomatic outcomes of three procedures for antireflux surgery performed at
      three specialist units. METHODS: Patients undergoing open Nissen fundoplication,
      laparoscopic Nissen fundoplication and laparoscopic anterior partial
      fundoplication between December 1993 and February 2001 were identified. Patient
      outcome was assessed by means of a postal questionnaire. This was a hypothesis
      generating study. RESULTS: Three hundred and fifty-seven patients (80.0 per cent)
      completed the questionnaire, with no differences in response rate between
      centres. Overall, a mean of only 7.6 per cent of patients reported a poor
      outcome. Logistic regression revealed no significant differences amongst the
      three procedures for any symptoms, after allowing for the effect of time. There
      was a general increase in the DeMeester score with increasing time from
      operation. The incidence of revisional reflux surgery was similar in the three
      groups. CONCLUSION: Medium-term symptomatic outcome following all three
      procedures was similar. There was some recurrence of symptoms of gastro
      oesophageal reflux with time for all procedures, suggesting that the effects of
      surgery diminish with time. The level of experience of the surgeon in a
      particular operation was more important than the procedure performed.

PMID- 15164443
TI  - Posterior laparostomy through the bed of the 12th rib to drain retroperitoneal
      infection after endoscopic sphincterotomy.
AB  - BACKGROUND: Duodenal perforation occurs in 0.4-1 per cent of endoscopic
      procedures. The best therapeutic approach for periampullary injury is
      controversial; initially the treatment is generally conservative, but sometimes
      large retroperitoneal infections develop that require surgery. METHODS: Six
      patients with an extensive retroperitoneal collection and unstable sepsis as a
      consequence of periampullary duodenal perforation sustained during endoscopic
      retrograde cholangiopancreatography were treated by right posterior laparostomy
      through the bed of the 12th rib. RESULTS: The sepsis was managed effectively by
      an open posterior approach, resulting in spontaneous closure of the duodenal leak
      after a mean(s.d.) of 14.5(5.2) days. No hospital death or major complication was
      recorded. Late incisional hernia developed in one patient. CONCLUSION: The
      technique of posterior laparostomy through the bed of the 12th rib provided
      adequate debridement and drainage of upper and lower parts of the retroperitoneal
      space involved by infection following periampullary duodenal perforation. Good
      control of retroperitoneal sepsis and duodenal secretions resulted in spontaneous
      closure of the duodenal leak, avoiding the need for more complex intra-abdominal
      procedures.

PMID- 15164444
TI  - Development of symptoms and complications in individuals with asymptomatic
      gallstones.
AB  - BACKGROUND: Gallbladder stones are common in the developed world. Complications
      of gallstones contribute substantially to healthcare costs and may be life
      threatening. The identification of individuals likely to develop complications
      would be of benefit in clinical practice as elective cholecystectomy could then
      be performed. METHODS: Seven hundred and thirty-nine subjects aged 35-85 years
      from the general population were screened for gallbladder problems by
      ultrasonography and questionnaire assessment of putative risk factors and
      digestive symptoms. Gallstones, cholesterolosis or sludge in the gallbladder were
      diagnosed in 123 (16.3 per cent) of 739 subjects, 120 of whom were followed for a
      median of 87 (range 3-146) months to May 2003 or until treatment was required.
      RESULTS: Fourteen patients were admitted to hospital and treated for gallstone
      related complications or symptoms. The cumulative risk of being treated during
      the first 5 years after detection of asymptomatic gallstones was 7.6 per cent and
      there was no indication of this risk levelling off. There were no significant
      differences between treated and untreated subjects with regard to digestive
      symptoms or any of the risk factors monitored at the initial screening, although
      treated subjects were significantly younger than those who were not treated.
      CONCLUSION: Nearly one in ten individuals with asymptomatic gallbladder stones in
      the general population may be expected to develop symptoms or complications that
      require treatment within 5 years. Age may be inversely related to the incidence
      of complications.

PMID- 15164445
TI  - Predicting the survival of patients with peritoneal carcinomatosis of colorectal
      origin treated by aggressive cytoreduction and hyperthermic intraperitoneal
      chemotherapy.
AB  - BACKGROUND: Peritoneal carcinomatosis in the absence of distant metastasis occurs
      in approximately 8 per cent of patients with colorectal cancer. Cytoreduction
      followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment
      option. Patient selection is crucial to outcome. METHODS: Cytoreduction followed
      by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The
      following factors were studied for association with survival: perforation and
      obstruction of the primary lesion, location of the primary lesion, obstruction
      associated with carcinomatosis, presentation, tumour differentiation and
      histological type. Extent of disease and completeness of cytoreduction were also
      studied. Hazard ratios (HRs) were used to study these factors. RESULTS: Location
      of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.)
      1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04
      to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i.
      1.21 to 4.16); P = 0.008) were associated with shorter survival. Important
      factors predicting survival were the number of affected regions (HR 1.38 (95 per
      cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR
      1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of
      cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other
      factor correlated with survival. CONCLUSION: The survival of patients with
      peritoneal carcinomatosis of colorectal origin is dominated by the extent of
      disease and the amount of residual tumour after cytoreduction.

PMID- 15164447
TI  - Sacral nerve stimulation for faecal incontinence in the UK.
AB  - BACKGROUND: Sacral nerve stimulation (SNS) is an effective therapy for faecal
      incontinence. Published studies derive largely from single centres and there is a
      need to determine the broader applicability of this procedure. METHODS:
      Prospective data were collected for all patients undergoing SNS in the UK.
      Records were reviewed to determine the outcome of treatment. RESULTS: In three UK
      centres 59 patients underwent peripheral nerve evaluation, with 46 (78 per cent)
      proceeding to permanent implantation. Of these 46 patients (40 women) all but two
      had improved continence at a median of 12 (range 1-72) months. Faecal
      incontinence improved from a median (range) of 7.5 (1-78) to 1 (0-39) episodes
      per week (P < 0.001). Urgency improved in all but five of 39 patients in whom
      ability to defer defaecation was determined, improving from a median of 1 (range
      0-5) to 10 (range from 1 to more than 15) min (P < 0.001). Maximum anal squeeze
      pressure and sensory function to rectal distension changed significantly.
      Significant improvement occurred in general health (P = 0.024), mental health (P
      = 0.008), emotional role (P = 0.034), social function (P = 0.013) and vitality (P
      = 0.009) subscales of the Short Form 36 health survey questionnaire. There were
      no major complications. One implant was removed. CONCLUSION: SNS is a safe and
      effective treatment, in the medium to long term, for faecal incontinence when
      conservative treatment has failed.

PMID- 15164446
TI  - Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients
      with peritoneal carcinomatosis of colorectal origin.
AB  - BACKGROUND: Colorectal cancer with peritoneal carcinomatosis is usually
      considered incurable. The purpose of this study was to evaluate the efficacy of
      intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in
      patients with colorectal carcinomatosis. METHODS: Between January 1989 and August
      2002, 53 patients (mean age 48.6 years) were treated by IPCH with mitomycin C.
      IPCH was performed in 34 patients following extensive cytoreductive surgery (more
      than two peritonectomy procedures). Five patients underwent two operations and
      one patient three operations. RESULTS: Operative morbidity and mortality rates
      were 23 and 4 per cent respectively. At a median follow-up of 59.5 months, the
      overall median survival was 12.8 months. The extent of carcinomatosis,
      completeness of cytoreduction and histological differentiation were significant
      prognostic indicators by univariate analysis. The median survival was 32.9 months
      for patients whose resection was classified as completeness of cancer resection
      (CCR) 0 (complete cytoreduction), 12.5 months for those whose operation was CCR-1
      (diameter of residual nodules 5 mm or less) and 8.1 months for patients who had a
      CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0.001).
      Completeness of cytoreduction was the only significant independent predictor of
      survival by multivariate analysis. CONCLUSION: IPCH combined with cytoreductive
      surgery seems to be an effective therapy for carefully selected patients with
      carcinomatosis from colorectal cancer. This strategy was most effective in
      patients with carcinomatosis of limited tumour volume or when cytoreductive
      surgery allowed sufficient downstaging (residual tumour nodules smaller than 5
      mm).

PMID- 15164448
TI  - Interleukin 13 and inflammatory markers in human sepsis.
AB  - BACKGROUND: Interleukin (IL) 13 is an anti-inflammatory cytokine that reduces
      inflammatory cytokine production, and enhances monocyte survival and MHC class II
      and CD23 expression. The only report of IL-13 in human sepsis noted no increase
      in IL-13 concentration, in contrast to animal data. This study further examined
      the expression of IL-13 in relation to human sepsis. METHODS: In a prospective
      observational study of 31 patients (24 men) with sepsis or septic shock, high
      sensitivity enzyme-linked immunoabsorbent assay (ELISA) was used to quantify
      levels of tumour necrosis factor (TNF) alpha on admission, and on days 1, 3, 5
      and 7 thereafter. IL-13 and IL-2 were assayed by standard ELISA, and HLA-DR on
      CD14-positive monocytes was measured by flow cytometry. RESULTS: Twenty-three
      patients developed septic shock. Monocyte HLA-DR levels showed greater depression
      and a slower recovery in shocked than non-shocked patients. The serum IL-13
      concentration was significantly higher in the shocked group from admission to day
      3, but subsequently decreased to levels similar to those in the non-shocked
      group. IL-13 concentrations were higher in non-survivors. The TNF-alpha
      concentration was higher in those with septic shock than in those without. The
      TNF-alpha level correlated with IL-13 concentration (r(S) = 0.61, P = 0.002). The
      IL-13/TNF-alpha ratio was greater in patients with shock than those with sepsis
      only (P = 0.017). IL-2 was undetectable. CONCLUSION: In human sepsis and septic
      shock, IL-13 correlated with TNF-alpha expression, but its effect on HLA-DR class
      II molecules remains unclear.

PMID- 15164449
TI  - Role of surgical portosystemic shunts in the era of interventional radiology and
      liver transplantation.
AB  - BACKGROUND: In the present era of liver transplantation and transjugular
      intrahepatic portosystemic shunts, the role and choice of shunt surgery for
      portal hypertension was reviewed. METHODS: This retrospective study analysed the
      management of patients with portal hypertension in a tertiary liver transplant
      unit between June 1993 and May 2002. During this 9-year interval, 394 patients
      underwent endoscopic control of varices, 235 transjugular intrahepatic
      portosystemic shunts were inserted, 1142 liver transplants were performed, while
      only 29 patients needed a surgical portosystemic shunt. RESULTS: Twenty-nine
      shunt operations were performed in nine patients with cirrhosis, one patient with
      congenital hepatic fibrosis and 19 without parenchymal liver disease. There were
      12 side-to-side lienorenal, nine mesocaval, three proximal lienorenal, two distal
      lienorenal, two portacaval and one mesoportal shunts. Encephalopathy was seen in
      five of 11 patients with a non-selective shunt, but did not occur after side-to
      side or selective lienorenal shunt procedures. At a median follow-up of 42.5
      months, one mesocaval shunt had thrombosed and one portacaval shunt had stenosed;
      both were successfully managed by percutaneous intervention. To date, six
      patients have died; two succumbed to postoperative complications, one of which
      was related to the shunt. CONCLUSION: Patients with Budd-Chiari syndrome and
      cirrhosis can nearly always be managed by a combination of endoscopy,
      interventional radiology and liver transplantation. In the rare instances when
      these therapies fail in patients with cirrhosis, a side-to-side lienorenal shunt
      is a good option.

PMID- 15164450
TI  - Effects of training and supervision on recurrence rate after inguinal hernia
      repair.
AB  - BACKGROUND: There is little information about the effects of operative experience
      and supervision of trainees on outcome in inguinal hernia surgery, one of the
      cornerstone operations of basic surgical training. METHODS: All primary inguinal
      hernia repairs carried out between 1994 and 2001 were registered prospectively in
      the Lothian Surgical Audit database. Subsequent problems that required re
      referral were identified from this database. Patients who required reoperation
      for recurrence a median of 3 (range 1-7) years after surgery were identified.
      RESULTS: Some 4406 repairs, including 90 recurrences (2.0 per cent), were
      identified. Open mesh, open sutured and laparoscopic techniques were employed.
      Senior trainees (registrars and senior registrars) had similar recurrence rates
      to consultants; supervision did not affect outcome. Junior trainees (senior house
      officers) had similar recurrence rates to consultants as long as they were
      supervised by either a senior trainee or a consultant. Unsupervised junior
      trainees had unacceptably high recurrence rates (open mesh: relative risk (RR)
      21.0 (95 per cent confidence interval (c.i.) 7.3 to 59.9), P < 0.001; open
      sutured: RR 16.5 (95 per cent c.i. 7.2 to 37.8), P < 0.001). CONCLUSION: Senior
      trainees may operate independently and supervise junior trainees, with recurrence
      rates equal to those of consultant surgeons. Junior trainees should be encouraged
      and given more practice in inguinal hernia repair with appropriate supervision.

PMID- 15164451
TI  - Hyperlipidaemia is positively correlated with lymph node metastasis in men with
      early gastric cancer (Br J Surg 2004; 91: 191-198).

PMID- 15164452
TI  - Letter 1: Late complications after ligation and bypass for popliteal aneurysm (Br
      J Surg 2004; 91: 174-177).

PMID- 15164453
TI  - Infection of patients by bloodborne viruses (Br J Surg 2004; 91: 395-399).

PMID- 15164454
TI  - Letter 2: Late complications after ligation and bypass for popliteal aneurysm (Br
      J Surg 2004; 91: 174-177).

PMID- 15164455
TI  - Inadvertent perforation during rectal cancer resection in Norway (Br J Surg 2004;
      91: 210-216).

PMID- 15164456
TI  - Hand-assisted laparoscopic live donor nephrectomy (Br J Surg 2004; 91: 344-348).

PMID- 15164457
TI  - Chronic anal fissure (Br J Surg 2004l; 91: 270-279).

PMID- 15164460
TI  - Proceedings of the Seventh International Congress on Toxoplasmosis. May 23-27,
      2003. Tarrytown, New York, USA.

PMID- 15164459
TI  - Proceedings of the third international meeting. Hepatocellular carcinoma: eastern
      and western experiences. November 21-22, 2002. Lodi Italy.

PMID- 15164461
TI  - Microscale reactors: nanoscale products.

PMID- 15164462
TI  - Proliferation of microfluidics in literature and intellectual property.

PMID- 15164463
TI  - Medicare's in good health.

PMID- 15164464
TI  - Fast-food lovers, unite!

PMID- 15164465
TI  - A shocking diagnosis.

PMID- 15164466
TI  - Unbelievable hype or documented science?

PMID- 15164467
TI  - Should dentists do oral sedation?

PMID- 15164468
TI  - You can now charge for local if you want (unless you're an oral surgeon).

PMID- 15164469
TI  - Good Joe, bad Joe; coffee's saga continues.

PMID- 15164470
TI  - Milestone Scientific and KaVo to develop injection device.

PMID- 15164471
TI  - FDA approves oral fluid rapid HIV test.

PMID- 15164472
TI  - A cavity-free life?

PMID- 15164473
TI  - The staff's role in the sale of a practice.

PMID- 15164474
TI  - Hepatitis C virus and dental personnel.

PMID- 15164476
TI  - Maximizing available options to embrace "less is best".

PMID- 15164475
TI  - Aesthetic restorations made predictable with new technology.

PMID- 15164477
TI  - Treatment planning for restorations. Available options.

PMID- 15164478
TI  - How do composite resins stand the test of time?

PMID- 15164479
TI  - Endodontic diagnosis. Mystery or mastery?
AB  - Review of 6 clinical distinctions: (1) Symptom: "anything under the sun."
      DIAGNOSIS: pulp exposure. Duplicate: clinical or radiographic pulp exposure
      evidence. TREATMENT: endodontics or pulp cap under strict protocol conditions.
      (2) Symptom: "cold." DIAGNOSIS: hyperemia. Duplicate: ice. TREATMENT: pulp
      protection or endodontics. (3) Symptom: "heat." DIAGNOSIS: pulpitis. Duplicate:
      heat. TREATMENT: pulpotomy for multirooted teeth or pulpectomy for single-rooted
      teeth. Schedule endodontic completion. (4) Symptom: "I recently had a toothache
      and now it is gone." DIAGNOSIS: necrosis. Duplicate: Electric Pulp Test and ice
      are negative. TREATMENT: endodontics. (5) Symptom: "I had a toothache awhile back
      and now it is gone." DIAGNOSIS: LEO. Duplicate: Electric Pulp Test, ice, and test
      cavity are negative. TREATMENT: endodontics. (6) Symptom: "It really hurts to
      touch my tooth." DIAGNOSIS: percussion. Duplicate: may or may not have a LEO and
      may or may not have cellulitis. TREATMENT: reduce occlusion, access cavity, water
      chew, and schedule to finish endodontics. If these tests are carefully performed,
      then they are objective and the doctor does not have to be in a subjective
      situation. A newfound sense of endodontic diagnostic mastery is experienced.
      Perhaps the best way to summarize the simplicity of this clinical diagnostic
      scheme is to quote Sherlock Holmes: "Nothing is more deceptive than the obvious."

PMID- 15164480
TI  - Silver cone re-treatment, or how to do the "hallway dance!".

PMID- 15164481
TI  - Optimizing the remaining dentition.

PMID- 15164482
TI  - Restoring the dento-gingival complex, Part 1.

PMID- 15164483
TI  - Endodontic treatment of reimplanted avulsed teeth.
AB  - By using an appropriate storage system such as a Save-A-Tooth and having
      knowledge of appropriate treatment options, an avulsed tooth can be reimplanted
      with the greatest chance of success. Using the different categories of avulsed
      teeth discussed in this article as a guide, the clinician can determine the most
      applicable course of treatment. If endodontic treatment is based on the clinical
      condition of the pulp and PDL cells, the chance of success following
      reimplantation is improved.

PMID- 15164484
TI  - Extraction site bone grafting in general dentistry. Review of applications and
      principles.
AB  - The clinician can successfully graft dental extraction sites to improve the
      aesthetics and function of the final restoration. When an extraction site
      receives a graft, ridge preservation is enhanced, pontic form can improve, dental
      implants can be placed in the correct position, and the prosthetic outcome will
      be enhanced.

PMID- 15164485
TI  - Collection correction. How to turn receivables into cash.

PMID- 15164486
TI  - Electronic scheduling. An underutilized software feature.

PMID- 15164487
TI  - Rhode Island's got the Blues. But the state's Blues plan isn't the only one
      drawing fire over its reserves, executive perks and compensation.
AB  - It's been a strained few months at Blue Cross and Blue Shield of Rhode Island.
      Outrage over corporate excess led to a flurry of reforms at the insurer, headed
      by Chairman Frank Montanaro, left, including banning loans to employees and
      dropping lavish perks. Other Blues have been catching flak for their burgeoning
      bottom lines, but executives say they need ample reserves since that's their only
      capital.

PMID- 15164488
TI  - A hospital divided. PPS proposal restricts LTACs in host hospitals.

PMID- 15164489
TI  - One step at a time on uninsured. Flurry of bills offered, but no immediate action
      seen.

PMID- 15164490
TI  - Public reporting. HCA naming suspected moratorium violators.

PMID- 15164491
TI  - New territory. Ardent to acquire Okla. system for $281 million.

PMID- 15164492
TI  - Alleged improprieties. Trial could affect hospital-drug company relationships.

PMID- 15164493
TI  - An unfunded mandate. The path to electronic records must be paved with someone's
      cash.

PMID- 15164494
TI  - The principles of going paperless. After decades of debate it is time to take
      action on electronic health records.

PMID- 15164495
TI  - Adding voltage to e-records. Action by White House, HHS and standards group HL7
      give electronic health records a strong jolt. Will momentum continue?

PMID- 15164496
TI  - Action and inaction. Election-year issues likely to impede IT bills' progress.

PMID- 15164497
TI  - By the numbers. Top healthcare software application providers. Ranked by 2003
      healthcare revenue.

PMID- 15164498
TI  - [Erythema nodosum in internal medicine].

PMID- 15164499
TI  - [Helicobacter pylori infection and stomach cancer].

PMID- 15164500
TI  - [Current issues regarding the complications of non-specific aorto-arteritis].

PMID- 15164501
TI  - [Clinical course of acute myocardial infarction and left ventricular function in
      long-term epidural analgesia].
AB  - The study of 76 patients with macrofocal myocardial infarction (MI) evaluated
      effects of epidural and standard analgesia on pumping capacity of the left
      ventricle (LV) and clinical course of MI. The study group consisted of 37
      patients exposed to long-term morphine-clopheline epidural analgesia. In the
      control 39 patients analgesia was induced conventionally (intravenous injection
      of morphine). Both groups received the same routine treatment. Long-term morphine
      clopheline epidural analgesia noticeably improves pumping LV function and
      clinical course of MI.

PMID- 15164502
TI  - [Circadian rhythms and seasonally dependent variability of arterial pressure in
      patients with arterial hypertension in the Khanty-Mansiysky region].
AB  - Key parameters of 24-h blood pressure monitoring (BPM) in 46 18-50-year-old
      patients (men and women) with arterial hypertension (AH) stage I, II and 33
      healthy persons living in the Tyumen North (Khanty-Mansiysky Region, the town of
      Nyagan) were investigated. The comparison group consisted of 55 patients with AH
      stage I, II and 33 healthy persons living in moderate climate (Tyumen) matched by
      sex, age, duration of AH, office systolic and diastolic arterial pressure (SAP,
      DAP). General patterns of 24-h and seasonal rhythms of AP fluctuations in healthy
      northerners and citizens of moderate climatic zone and mismatch of these rhythms
      in AH patients more evident in the northerners are shown. Paired correlations
      were obtained which indirectly confirm the priority role of daily AP rhythm in
      development of visceral lesions irrespective of the season of the year and
      climatic load. In the North, when winter meets spring, a surge of SAP, DAP and
      mean AP occurs as well as an increase in heart rate, number of patients with
      disturbed circadian profile of AP. In moderate climate these changes are more
      typical for summer period. The results of the study necessitate design of
      programs of additional pharmacological and preventive measures for hypertensive
      northerners with consideration of AP seasonal rhythms and climatic load.

PMID- 15164503
TI  - [Serum lipoproteins in different types of obesity in lipid loading challenge].
AB  - The impact of food fat load on plasmic lipid transport system (LTS) was studied
      in persons with abdominal and gluteofemoral obesity by the standard fat test
      proposed by J. Patsch. The lipoprotein spectrum in abdominally obese patients was
      characterized by high atherogenicity of lipoprotein spectrum on an empty stomach
      aggravating under fat intake: prolongation of postprandial lipemia up to 6 hours
      with growing apoB and apoB/A1. Patients with gluteofemoral obesity differed from
      normal weight persons only by higher fasting values of triglycerides. They showed
      no atherogenic trend in changes in response to food fat.

PMID- 15164504
TI  - [Changes of thyroid hormone levels in the progression of coronary
      arteriosclerosis].
AB  - The study concerned changes in the levels of thyroid hormones (T3, T4) and their
      proportional relations in the serum of peripheral venous blood of patients with
      ischemic heart disease (IHD) with reference to severity of coronary and
      myocardial insufficiency and clinical symptoms. Thyroid hormones (TH) were
      examined in patients with stenosing atherosclerosis of the coronary arteries with
      incipient angina pectoris (IAP), acute myocardial infarction (AMI), chronic IHD
      before and after MI and postinfarction myocardial dysfunction (PIMD) depending on
      severity of coronary atherosclerosis. The findings were compared to hemodynamic
      and metabolic myocardial parameters, severity of coronary atherosclerosis
      assessed at coronaroangiography. It is shown that TH concentrations depend on
      efficiency of coronary circulation and characteristics of myocardial metabolism.
      IHD patients have isometric TH levels before MI, conversion of T4 into T3 being
      inhibited. After MI and development of PIMD at the compensation stage T4 and T3
      levels lowered under control levels. This reflects intensity and pattern of
      metabolic processes in the myocardium. In intact myocardial function T4/T3 in the
      above patients was above the control levels because of high concentration of
      serum T4. In development of acute coronary syndrome the level of T3 fell while
      that of T4 went up due to suppression of its deiodination.

PMID- 15164505
TI  - [Adrenergic vascular reactivity in elderly hypertensive patients with orthostatic
      disorders].
AB  - Vascular adrenergic reactivity was studied in 100 healthy persons and 222 elderly
      patients with stage II essential hypertension at high risk of complications. With
      age, the rate of orthostatic hypotension rises. This hypotension in the elderly
      hypertensive patients is caused by reduced adrenergic reactivity of venous
      microvessels.

PMID- 15164506
TI  - [Pre-hospital factors of in-hospital mortality of myocardial infarction].
AB  - The time of referral for medical care, results of prehospital diagnosis and
      hospital myocardial infarction (MI) lethality were studied in 1138 inpatients.
      Early referral (within 6 hours of the disease onset) was in 61.9% cases.
      Hypodiagnosis was registered in 15.6%. Hospital lethality in MI was 14.7%. By age
      groups: 45-59 years--4.9%, 60-74 years--13.0%, 75 years and older--21.1% (p <
      0.01); in women--12.1%, in men 16.0% (p < 0.05); in first and second MI--10.3 and
      19.2%, respectively (p < 0.05), in typical and atypical MI--13.9 and 16.6% (p <
      0.05), respectively. In early and late referral in patients with macrofocal MI
      hospital lethality reached 19.3 and 11.7% (p < 0.05), respectively. In early
      referral hypodiagnosis of macrofocal MI did not increase lethality. In late
      referral lethality was higher (p < 0.05) in the presence of hypodiagnosis
      (11.7%).

PMID- 15164507
TI  - [Prediction of brain infarction in hypertensive patients].
AB  - A 7-year prospective study of 379 hypertensive patients was conducted with
      primary comprehensive clinical and device examination of the patients in hospital
      followed by annual control in hospital or outpatient setting. Two groups were
      formed: with uncomplicated essential hypertension (EH)(n = 263, group 1); with EH
      complicated by brain infarction (BI) (n = 116, group 2). Overall prognostic
      correctness was 85.9%. BI was predicted by age, smoking, high intake of salt,
      absence of regular antihypertensive therapy, non-dipper pattern, low output,
      atherosclerotic changes of major head arteries, frequent paroxysms of cardiac
      fibrillation, ventricular extrasystole, abnormal blood rheology. Integral index
      of the patient condition calculated on the basis of the decisive prognosis rule
      (data of the primary examination + MI within 7-year follow-up) enables targeted
      prevention of cerebral complications.

PMID- 15164508
TI  - [Structural and functional cardiac changes and sex hormone levels in men with
      sexual dysfunctions].
AB  - 44 men with chronic prostatitis were examined for structural-functional heart
      alterations with reference to severity of erectile dysfunction (ED). Sex hormones
      were also estimated. Control group consisted of 20 healthy men. Doppler
      echocardiography, 24-h monitoring of arterial pressure (AP) and ECG, finger and
      ultrasound investigation of the prostatic gland and microscopy of its secretion
      were made. Blood plasm testosteron, prolactin and dehydroepiandrosterone-sulphate
      were estimated by enzyme immunoassay. Erectile function was assessed by the
      questionnaire "International index of erectile function". Thus, sexual hormone
      changes associated with sexual dysfunction in men promote left ventricular
      diastolic dysfunction. The type of intracardiac hemodynamics in this case is, as
      a rule, restrictive.

PMID- 15164509
TI  - [The condition of peripheral arteries in patients with systemic lupus
      erythematosus].
AB  - To evaluate the condition of peripheral arteries and its correlations with blood
      lipid spectrum and intake of glucocorticoids (GC), 53 female patients with SLE
      entered the study. Of them, 20 patients were GC untreated (group 1) while 33 ones
      took GC for a long time (group 2). Nine of 20 (45%) patients and 9 of 33 (27%)
      patients of group 1 and 2, respectively, had antiphospholipid syndrome (APS).
      Ultrasonography examined common carotid arteries (CCA), brachial arteries (BA),
      femoral arteries (FA) with measurement of the thickness of the intima-media
      complex (IMC). Lipid spectrum was examined with standard enzyme assay using kits
      by Boehringer Mannheim GmbH (Germany). Atherosclerotic plaques of carotid
      arteries were detected only in group 2. CCA IMC thickness reached 0.78 +/- 0.17
      and 0.75 +/- 0.16 mm in groups 1 and 2, respectively. This thickness was
      significantly greater in SLE patients with APS than free of APS (0.89 +/- 0.18
      and 0.87 +/- 0.18 mm in groups 1 and 2, respectively; 0.72 mm on the average in
      both groups, p = 0.02). Patients of group 1 with dyslipidemia showed a
      significant increase in CCA IMC (0.84 +/- 0.18 mm) vs patients with
      normolipidemia (0.70 +/- 0.13 mm, p = 0.042). Significantly increased levels of
      cholesterol, LDLP cholesterol and triglycerides were recorded in SLE patients of
      group 1 with CCA IMC > 0.8 mm. In group 1 there were significant positive
      correlations between CCA IMC and levels of total cholesterol, LDLP cholesterol,
      triglycerides (r = 0.78, 0.76 and 0.66 respectively, p < 0.05). Thus,
      atherosclerotic affection of the peripheral arteries in SLE is associated with
      long-term course of the disease, APS, dyslipidemia and intake of GC.

PMID- 15164510
TI  - [Immune parameters in patients with chronic hepatitis C and with various
      histologic changes].
AB  - Levels of cytokines (IL-1, IL-2, IL-4, IL-6, TNF) were studied in 22 patients
      with chronic hepatitis C (CHC) under different value of histological activity
      index (HAI). Cytokines were measured in peripheral blood by enzyme immunoassay
      using kits produced by Proteinovy Kontur (St-Petersburg). Morphological
      examination of hepatic biopsies was made with estimation of HAI by R. Knodell and
      fibrosis degree by V. Desmet. CHC patients with a high HAI were found to have
      higher levels of gamma-globulines and gamma-GTP. No significant correlation was
      revealed between HAI and content of transaminases. CHC patients with definite
      inflammatory infiltration of the portal tracts, intralobular degeneration,
      hepatic necrosis had higher indices of proinflammatory mediators of immune
      response IL-1, IL-2, IL-6 and TNF-alpha. In severe hepatic fibrosis there were
      higher values of IL-1, IL-2, IL-6. IL-4 was higher in patients with weak
      inflammatory infiltration, intralobular degeneration, lobular necrosis, mild
      fibros. The latter was associated with high interferon-alpha. Thus, serum
      cytokines concentrations and morphological changes in the liver correlate.

PMID- 15164512
TI  - [Correction of hyperlipidemia with Allicor].
AB  - The hypocholesterolemic action of long-acting garlic powder tablets Allicor was
      investigated in a double-blind placebo-controlled study in men with mild
      hypercholesterolemia. Group 1 received allicor in a daily dose 600 mg, group 2
      received placebo. The results show that allicor lowers total cholesterol, LDLP
      cholesterol, raises HDLP cholesterol and therefore can be recommended for
      correction of lipid content in patients with moderate hyperlipidemia.

PMID- 15164511
TI  - [Pharmacodynamics of nonessential amino acids in elderly patients with post
      infarction cardiac sclerosis].
AB  - We studied pharmacodynamics of an amino acids complex (AAC) in 60 elderly
      patients (a mean age 71.6 years) with ischemic heart disease, postinfarction
      cardiosclerosis (PIC), circulatory insufficiency stage I-II. The patients were
      randomized into 3 groups, 20 persons each. Group 1 received standard therapy (ST)
      and placebo, group 2--ST + AAC (one tablet of 70 mg 3 times a day), group 3--ST +
      AAC sublingually in the same dose. Clinical symptoms, results of ECG Holter
      monitoring and echocardiography were assessed before the treatment and on
      treatment day 18. Positive effects of AAC used in combination with ST in relation
      to clinical symptoms, myocardial contractility and ischemia. No differences in
      efficacy were observed with oral and sublingual AAC administration.

PMID- 15164513
TI  - [Cardiometabolic therapy of ischemic heart disease].
AB  - A total of 59 patients suffering from ischemic heart disease with effort angina
      (functional classes II-IV) entered the study. Of them, 29 patients received
      antianginal drugs and 10-day courses of a combination of drugs with membran
      oprotective properties (MPD); 30 patients received antianginal drugs alone. Blood
      levels of lipid peroxidation products, lipid structure of erythrocytic membrane,
      exercise tolerance were studied before and after the treatment. MPD therapy was
      associated with lower activity of lipid peroxidation, stabilization of cell
      membrane structure and greater exercise tolerance due to more effective cardiac
      performance.

PMID- 15164514
TI  - [Causes of hospitalization of non-tuberculous patients in a tuberculosis
      hospital].
AB  - In present epidemiological and economic conditions tuberculosis suspects should
      be hospitalized to specialized tuberculosis hospitals only after they are
      carefully examined for cancer of the lungs and lingering pneumonia. For this an
      obligatory diagnostic minimum should be introduced.

PMID- 15164515
TI  - [The topic of heart failure at the 25th European Congress of Cardiologists].

PMID- 15164516
TI  - [Development of new technology for isolation of nebramycin complex antibiotics
      from the cultural fluid].
AB  - A new technology for nebramycin complex antibiotics isolation from non-filtered
      culture fluid was developed. The industrial use of the technology permitted to
      exclude the stage of the culture fluid filtration, to increase the yield by more
      than 33% and to reduce the time of the process by 1.7 times.

PMID- 15164518
TI  - [Effect of novel natural hypolipidemic compounds on human immunodeficiency
      virus].
AB  - Target screening among microbial products resulted in isolation of hypolipidemic
      compounds tested for activity against HIV in culture of transferable
      lymphoblastoid cells MT-4. The majority of the compounds showed antiviral
      activity. The highest antiviral effect was observed when before exposure to the
      virus the cells were preincubated for 1 hour in the presence of the isolated
      compounds. The compounds showed no effect when added to the cell culture
      preliminarily infected by HIV.

PMID- 15164517
TI  - [Detection of sulfamethoxazole by a piezoquarz immunosensor].
AB  - A mass susceptible immunosensor for FIA of sulfamethoxazole residues in liquid
      products was designed. The immunosensor is based on piezoelectric transducer.
      Hapten-protein conjugate (SMX-Diazo-BSA) immobilized on the preliminarily
      silanized electrode surface of piezoelectric quartz crystal was used as the
      bioreceptor coating. Optimization of the FIA conditions permitted to develop a
      simple and express procedure for one-step detection of sulfamethoxazole in a
      sample and further regeneration of the bioreceptor layer. The measuring ranges
      are 1 to 50 ng/ml and the detection limit is 0.15 ng/ml. The detection results
      were compared with the HPLC data. The advantages of the new procedure are its
      simplicity and rapid provision of the analysis results, possible direct detection
      of the analyte without additional label and repeated use of the bioreceptor
      layer. The new immunosensor was applied to testing of various milk specimens. It
      was shown that the quantity of sulfamethoxazole in all the specimens was lower
      than the recommended Euroresidue standards (100 ng/ml).

PMID- 15164519
TI  - [Efficacy of plague prophylaxis with streptomycin, tetracycline, and rifampicin
      in simultaneous immunization of white mice by resistant EV NRIEG strain].
AB  - Tetracycline, doxycycline, streptomycin and rifampicin were used for prophylaxis
      of experimental plague in albino mice (Yersinia pestis 231, approximately 1000
      LD50). The antibiotics were administered 5 hours after the infection for 5 days.
      Tetracycline and doxycycline provided survival of 60 to 75% of the animals, while
      the respective figure for streptomycin and rifampicin was 100%, but streptomycin
      and rifampicin inhibited development of plague immunity evident from a lower
      protection index (PI) by 3-4 orders. The PI for the tetracyclines lowered by 2
      orders. Simultaneous prophylaxis with the tetracyclines and immunization by Y.
      pestis EV Rifr R(SmTc) (10(6) microbial cells) provided not only higher
      percentage of the animal survival (80-90%) but also development of sufficient
      plague immunity: PI of 1.0 x 10(5)--5.0 x 10(5). When the animals were infected
      with Y. pestis 231 R(SmTc) the use of the tetracyclines failed, whereas the use
      of doxycycline and simultaneous vaccination by EV Rifr R(SmTc) provided survival
      of 70-85% of the animals. Successive use of inefficient streptomycin (for 2 days)
      and efficient rifampicin (for 3 days) provided survival only of 30% of the mice.
      A similar regimen of the successive use of the inefficient and efficient
      antibiotics (the total term of 5 days) started simultaneously with immunization
      by EV Rifr R(SmTc) provided survival of 80% of the animals. The use of combined
      specific and urgent prophylaxis of plague infection due not only to antibiotic
      susceptible but also to antibiotic resistant strains of the plague pathogen was
      shown promising.

PMID- 15164520
TI  - [Use of clarithromycin in the treatment of atopic dermatitis complicated by
      staphylococcal infection].
AB  - Thirty patients (19 boys and 11 girls) with atopic dermatitis complicated by
      pyodermia were treated with clarithromycin tablets (Fromilid, KRKA, Slovenia) in
      a dose of 7.5 mg/kg body weight twice a day. The average treatment course was 7
      days. The severity of atopic dermatitis was evaluated by the SCARAD Index. Thirty
      patients of the reference group were treated with intramuscular lincomycin in a
      dose of 10-20 mg/kg body weight twice a day for 7 days. The difference in the
      average SCORAD Index before and after the treatment with clarithromycin amounted
      to 19.95 vs 14.68 (p < 0.005) with the use of lincomycin. The tolerance of
      clarithromycin was good.

PMID- 15164521
TI  - [3-Year experience of use of cefepime (Maxipime) for the treatment of hospital
      infections in a specialized surgical hospital].
AB  - Microbiological and clinical monitoring for 3 years (from 2001 to 2003) confirmed
      high clinical and microbiological efficacy of cefepime (Maxipime, Bristol-Myers
      Squibb) in the treatment of infectious complications in patients with solid
      tumors in an oncologic hospital. It should be noted, however, that high efficacy
      of cefepime and wide ranges of the indications to its use do not allow to
      consider it as an agent for the treatment of all possible complications in such
      patients. The drug is not active against enterococci, not always clinically
      sufficiently effective in the treatment of Pseudomonas aeruginosa infections, it
      is impossible to use cefepime in monotherapy of suspected anaerobic infections.
      Therefore, widespread uncontrolled use of cefepime should be prohibited. It
      should be prescribed strictly by the indications with the account of the pathogen
      susceptibility, the infection severity and the recommended doses and regimens.
      The use of cefepime is undoubtedly valid when other antimicrobials fail or when
      empirical antimicrobial therapy of severe cases is required, including those
      under intensive care.

PMID- 15164522
TI  - [Analysis of parameters of the antibacterial treatment of acute otitis media in
      adults: results of a multicenter study].
AB  - The programme was aimed at audit of the parameters of antibacterial therapy for
      acute otitis media in adult outpatients in 8 cities of Russia (Smolensk,
      Volgograd, Ekaterinburg, Yaroslavl, Nizhny Novgorod, Tyumen, Ryazan,
      Vladivostok). The information sources were the case records. The data from the
      records were structurally fixed in specially designed individual registration
      charts for further computer processing. The analysis of the results showed that
      the real practice of the antibacterial therapy for acute otitis media was not
      based on a unique approach and did not mainly correspond to the present
      standards. Ampicillin proved to be preferential, whereas it is known that the
      drug of choice for such cases is amoxicillin. Antibacterial agents with low
      activity against the basic pathogens of the infection (doxycycline and others)
      and high toxicity (co-trimoxazol) were often prescribed, while the recommended up
      to-date antibiotics (amoxicillin/clavulanate and others) were prescribed
      extremely rare or not prescribed at all. Scientifically unreasonable combined
      antibiotic therapy and prescription of parenteral drugs not rational for the
      treatment of outpatients were practiced.

PMID- 15164523
TI  - [Activation of macrophages by plant polysaccharides].

PMID- 15164525
TI  - Portal biliopathy: emerging management problems.

PMID- 15164524
TI  - [Aminoglycoside antibiotics and the inner ear: toxicity, idiosyncrasy or
      frequency resonance?].

PMID- 15164526
TI  - Advances in immunosuppressive therapy in solid organ transplantation.

PMID- 15164527
TI  - Transcatheter arterial chemoembolization in hepatocellular carcinoma: technique,
      effects and present status.

PMID- 15164528
TI  - Association of human leucocyte DR and DQ antigens in Crohn's disease in Asian
      Indians: a family study.
AB  - The pathogenesis of Crohn's disease (CD) involves an abnormal immune response to
      enteric bacteria in genetically susceptible individuals. There are no family
      studies regarding the association of CD with human leucocyte antigens (HLA) class
      II. In the present study, we have studied the association of HLA class II
      antigens in patients with CD and their first-degree relatives. Nine patients with
      CD and their first-degree relatives were studied. A group of 110 healthy
      unrelated and ethnically matched subjects were used as controls. Molecular HLA
      typing was done using the sequence-specific primer-based method. The transmission
      disequilibrium test (TDT) was used to analyze the results. A total of 65
      individuals were included in the study; 52/56 first-degree relatives (92.8%) of 9
      patients with CD consented to the study. The median age of patients was 40 years.
      When the distribution of the HLA class II antigens in patients was compared to
      that in controls no significant differences were observed even after applying the
      Yates correction. As the sample size of the population was small, the association
      of CD with DR and DQ alleles was further analyzed by using the TDT. Even after
      applying TDT, no significant association was observed. Familial aggregation of CD
      is uncommon in India. Crohn disease is not associated with HLA class II antigens
      in Indian patients. Genes of the major histocompatiblity complex are likely to
      contribute little to the susceptibility to Crohn disease in Indian patients.

PMID- 15164529
TI  - Effects of malnutrition on the digestive enzymes of the large bowel of young
      rhesus monkeys.
AB  - The aim of the present study was to investigate the effect of mild-to-moderate
      protein-energy malnutrition (PEM) and rehabilitation on the digestive enzymes of
      the large bowel in young rhesus monkeys. The presence of these enzymes has
      already been reported in the large bowel by many authors. The activities of the
      digestive enzymes, i.e. lactase, sucrase, maltase, trehalase, glucoamylase,
      leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase,
      from different parts of the large bowel were determined in 6 controls, 6 PEM and
      6 rehabilitated young rhesus monkeys. These monkeys had been used to study the
      effect of malnutrition on the small intestine and the results have already been
      published. There was a significant decrease in the sucrase in the ascending colon
      (p < 0.05); maltase in all the parts of the large bowel (p < 0.05); and
      glucoamylase activities (p < 0.05) in the caecum segment of the large bowel in
      the PEM group. The activity of other enzymes, i.e. lactase, trehalase, alkaline
      phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase, was
      unaffected in the PEM group. The changes in the enzyme activities recovered on
      rehabilitation of 21 weeks. The result of this study suggest that even mild-to
      moderate malnutrition affects the enzyme activity of the large bowel, which
      recovers on rehabilitation.

PMID- 15164530
TI  - Prevalence, risk factors and genotype distribution of HCV and HBV infection in
      the tribal population: a community based study in south India.
AB  - Viral hepatitis caused by the hepatitis C virus (HCV) and hepatitis B virus (HBV)
      represents a major public health problem in India. These viruses share common
      modes of transmission, such as parenteral routes. We aimed to assess the exposure
      of a tribal population to these viruses in south India. The present study was
      carried out on serum samples from 890 individuals (526 males and 324 females)
      belonging to the Lambada tribe residing in the state of Andhra Pradesh, south
      India. Anti-HCV antibody and hepatitis B surface antigen (HBsAg) status in the
      sera were analyzed using commercially available enzyme immunoassays (Abbott Labs,
      Chicago, IL). HCV-RNA and HBV-DNA in the sera was tested by reverse transcriptase
      polymerase chain reaction (RT-PCR) and PCR, respectively. The infecting genotype
      of HCV was determined using type-specific primers corresponding to the NS5 region
      of the virus. Out of the 890 samples, 18 (2.02%; male 11/526; female 7/364) were
      positive for HCV-RNA by RT-PCR and, 17 of them were positive for anti-HCV
      antibody. Genotyping of HCV isolates from the 18 individuals positive for HCV-RNA
      revealed that 66.67% (12/18) were infected with type 1 of HCV and its variants;
      while in the remaining (6/18), the infecting genotype was found to be type 3 and
      its variants. A total of 46 samples (5.16%; males 28/526; female 18/364) were
      positive for HBsAg; while 11 were positive only for HBV-DNA, 9 were positive for
      both hepatitis B e antigen (HBeAg) and HBV-DNA. Cultural practices such as
      tattooing, traditional medicine (e.g. blood-letting), rituals (e.g.
      scarification), body-piercing etc are the potential sources of spread of
      infection in this tribe. None of the samples analyzed revealed co-infection with
      the 2 viruses.

PMID- 15164531
TI  - Prevalence of hepatitis B surface and e antigens, risk factors for viral
      acquisition and serum transaminase among blood donors in Ibadan, Nigeria.
AB  - The objective of this study was to determine the prevalence of hepatitis B e
      antigen (HBeAg) in blood donors with hepatitis B surface antigen (HBsAg), and
      alaninine transaminases (ALT) levels and possible risk factors for the
      transmission of hepatitis B virus (HBV). Over a 6-month period, consecutive blood
      donors were screened for HBsAg, HBeAg, ALT and risk factors for HBV transmission.
      One hundred seventy-five adults (158 males, 17 females) were screened. Thirty
      seven (21.3%) were HBsAg positive, 4 (2.3%) were HBeAg Positive and 17 (9.7%) had
      a raised ALT level, which ranged between 42-126 IU/L. All the HBeAg-positive
      subjects had raised ALT levels. The main risk factors among others, were
      scarification and indiscriminate injections. Twenty of the 37 HBsAg-positive
      subjects (54%) had no identifiable risk factor. The present study revealed that,
      HBeAg positivity among HBsAg positive blood donors was infrequent and whenever
      present was associated with active liver disease indicated by raised ALT value.

PMID- 15164533
TI  - Acute pancreatitis associated with acute hepatitis E infection.
AB  - A 45-year-old male presented with severe abdominal pain, hyperamylasaemia and a
      bulky pancreas. In addition, he had deep jaundice and markedly raised serum
      transaminases, and his serum was positive for IgM anti-hepatitis E virus (HEV)
      antibodies. The common aetiologies of acute pancreatitis were excluded. The
      patient ran a benign course for both acute viral hepatitis and acute
      pancreatitis, and recovered completely. Acute pancreatitis caused by HEV
      infection has been reported only occasionally.

PMID- 15164532
TI  - Unusual presentation of enteric fever: three cases of splenic and liver abscesses
      due to Salmonella typhi and Salmonella paratyphi A.
AB  - Enteric fever is a multisystem disorder caused mainly by Salmonella typhi and
      Salmonella paratyphi A. It continues to be a major public health problem,
      especially in developing countries. Unusual presentations of Salmonellosis are
      rare. We report 3 such cases of young adult males, one of splenic abscess due to
      Salmonella typhi and one each of liver abscess due to Salmonella typhi and
      Salmonella paratyphi A. A brief review of the literature pertaining to the cases
      is also given.

PMID- 15164534
TI  - Anterior or posterior gastro-jejunostomy with truncal vagotomy for duodenal ulcer
      -are they functionally different?
AB  - Truncal vagotomy with gastrojejunostomy (GJ) is the standard treatment for
      chronic cicatrizing duodenal ulcer with gastric outlet obstruction. We tried to
      determine if a significant functional difference exists in the early and late
      outcomes following anterior and posterior types of GJ to treat this condition.
      The case records of 106 patients who underwent truncal vagotomy and GJ at our
      institute from 1 January 1995 to 31 December 1999 were studied retrospectively.
      Patients were followed up with a personal interview. Perioperative and long-term
      parameters were compared in the anterior and posterior G.I. groups. Sixty-five
      patients (61.32%) were followed up; 31 in the anterior group and 34 in the
      posterior group. The median follow-up was 5 years (range 2.5-7.5 years). Except
      for a significant difference in length of afferent loop (p < 0.0001), there were
      no significant differences in the duration of hospital stay, nasogastric
      aspirates on postoperative days 1, 2, 3 and 4 and the day the nasogastric tube
      was removed. Early postoperative complications were uncommon and not different in
      the two groups and long-term outcomes were similar. The Anterior GJ, being
      technically easier and needing less operative time, may be advocated in all cases
      of chronic duodenal ulcer, with gastric outlet obstruction requiring truncal
      vagotomy and drainage.

PMID- 15164535
TI  - Evaluation of long-term results of choledochoduodenostomy for benign biliary
      obstruction.
AB  - The role of choledochoduodenostomy (CDD) in the management of lower common bile
      duct (CBD) obstruction is controversial because of the long-term complications
      such as ascending cholangitis, sump syndrome and alkaline reflux gastritis. In
      spite of the good long-term results observed in some studies, CDD is considered a
      last trial for lower CBD obstruction. This study was done to analyze the efficacy
      and long-term results observed in patients who underwent CDD. A total of 21
      patients who underwent side-to-side CDD for various causes of lower CBD
      obstruction from 1992 to 2002 in our institute were analyzed retrospectively.
      Symptoms, indications and complications were noted from the hospital records.
      Long-term follow-up evaluation was done through personal communication,
      examination, and subsequent ultrasonography and endoscopy in symptomatic
      patients. The most common presenting symptom was abdominal pain (95.2%) and the
      most frequent indication for CDD was multiple CBD stones (61.9%). Eighteen of the
      21 patients (85.7%) had a normal postoperative recovery without any
      complications. One patient (4.8%) had an anastomotic leak and peritonitis, and 2
      (9.5%) had wound infection. Long-term follow-up was possible in only 15 patients
      as the others were lost to follow-up. Nine patients (60%) were asymptomatic and 6
      (40%) were occasionally symptomatic (abdominal pain and bilious vomiting), to an
      extent which did not affect their day-to-day life. Recurrent or retained stones
      were not noted, in any patient. All 6 symptomatic patients showed duodenogastric
      reflux but alkaline reflux gastritis was seen in only 1 patient (6.66%).
      Anastomotic stoma was patent in all the patients subjected to endoscopy. Features
      of cholangitis or sump syndrome were not noted in any patient. Side-to-side CDD
      is a safe and definitive procedure for the decompression of lower CBD
      obstruction. It has good long term results with infrequent complications.

PMID- 15164536
TI  - Intestinal lipoma: a rare cause of lower gastrointestinal haemorrhage.
AB  - Lower gastrointestinal bleeding from submucosal lipomas of the intestine is very
      rare. We report our experience with 3-patients presenting with lower
      gastrointestinal haemorrhage who were detected to have no cause other than
      intestinal lipomas. In two of these patients, the lipoma was in the small
      intestine and presented with chronic blood loss or recurrent episodes of
      bleeding. The third patient presented with massive haematochyzia and had a number
      of lipomas in the cecum and right colon. The diagnosis was established by
      laparotomy and intraoperative enteroscopy in 2 cases, and by colonoscopy and
      laparotomy in the third. Surgical excision of the lipoma led to cure in all the
      patients. We conclude that when laparotomy and intraoperative enteroscopy fail to
      show any cause for bleeding other than an innocuous-looking lipoma, it should be
      excised. The literature has been reviewed.

PMID- 15164537
TI  - Mesenteric and portal vein thrombosis presenting as acute intestinal obstruction.
AB  - Acute bowel infarction is a major complication in patients with superior
      mesenteric vein and portal vein thrombosis. However, in some patients, sufficient
      collaterals can prevent acute bowel infraction. We present a case of mesenteric
      vein and portal vein thrombosis with intestinal obstruction due to acute bowel
      oedema and ischaemic adhesion without infarction or stenosis.

PMID- 15164539
TI  - Efficacy of endoscopic wire guided biliary brushing in the evaluation of biliary
      strictures.
AB  - Endoscopic brush cytology is a valuable technique for the evaluation of biliary
      strictures. The sensitivity of this technique varies from 30% to 83%, however, it
      can have specificity of 100%. We retrospectively evaluated the usefulness of wire
      guided biliary brush cytology in biliary strictures in our hospital over a 3
      years period from 1997 to 2000. Brushings from 58 biliary strictures were
      obtained during endoscopic retrograde cholangiography. They were compared with
      histological proof obtained by surgical biopsy or percutaneous fine-needle
      aspiration cytology and/or clinical findings. These were reported as benign or
      malignant. Eleven patients were excluded due to incomplete data. Eighteen
      patients had benign brushings. Fourteen of the 29 patients in whom histological
      confirmation of malignancy brushings was obtained were also reported as
      malignant. The sensitivity of endoscopic brushings was 48.2%, specificity 100%
      and diagnostic accuracy 55.2%. No major complications were seen in our study
      group.

PMID- 15164540
TI  - Too close for comfort? Appointment of Blues exec as head of board overseeing Iowa
      system resurrects questions about corporate conflicts of interest.
AB  - What happens when a top insurance executive also serves on a hospital-related
      board? In Iowa, where Wellmark Chairman John Forsyth is leading the board
      overseeing the University of Iowa Hospitals and Clinics, observers say it's
      sometimes difficult to avoid potential conflicts. Concerns also crop up for Joel
      Allison, left, head of Baylor Health Care System, who serves on the board of an
      Abbott spinoff.

PMID- 15164538
TI  - Bleeding gastric lipoma: case report and review of the literature.
AB  - We present a rare case of a bleeding gastric lipoma diagnosed by computed
      tomography. Surgical treatment was followed by an uneventful recovery.
      Histopathological confirmed the diagnosis.

PMID- 15164541
TI  - Tooting their own horns. AHA to show Washington what hospitals are worth.

PMID- 15164542
TI  - Operating without a budget. Heart programs adding on but not adding up finances.

PMID- 15164543
TI  - Force to be reckoned with UnitedHealth-Oxford could dominate northeast.

PMID- 15164544
TI  - Patient privacy safe, for now.

PMID- 15164545
TI  - Lurching into the future. Bush sets 2014 goal for EMRs, calls for incentives.

PMID- 15164546
TI  - The real ROI is from the NIH. Clinical research cuts may slow effort to improve
      care and cut long-term costs.

PMID- 15164547
TI  - Lost in translation. Professional interpreters needed to help hospitals treat
      immigrant patients.

PMID- 15164548
TI  - Long-range forecast: partly healthy, chance of storms. Health plans use
      sophisticated modeling to help predict members' health risks, cost of care. But
      privacy issues cloud technology's future.

PMID- 15164549
TI  - Boardroom via courtroom. Former county prosecutor, administrator putting skills
      to work as Detroit Medical Center's new CEO.

PMID- 15164550
TI  - My morning run is a moving meditation.

PMID- 15164551
TI  - Putting it all together.

PMID- 15164552
TI  - Fresh weapons for an old battle.

PMID- 15164553
TI  - Women, cigarettes and death.

PMID- 15164554
TI  - Have it your way: redesigning birth.

PMID- 15164555
TI  - An unspeakable affliction.

PMID- 15164556
TI  - Health for life M.D.: our doctor's advice.

PMID- 15164557
TI  - How to think about HT.

PMID- 15164558
TI  - No time for wrinkles.

PMID- 15164559
TI  - A better sex life.

PMID- 15164560
TI  - The more social sex.

PMID- 15164561
TI  - Alcohol's deadly triple threat.

PMID- 15164562
TI  - A worldwide gender gap.

PMID- 15164563
TI  - Broke and broken.

PMID- 15164564
TI  - A deadly disease, a promising drug.

PMID- 15164565
TI  - It's a mystery, but it clearly makes us smarter and healthier.

PMID- 15164566
TI  - A nation's wake-up call.

PMID- 15164567
TI  - The rise of the gay family.

PMID- 15164568
TI  - An overview of sterolithography (STL).

PMID- 15164569
TI  - Development and evaluation of sentinel node biopsy: a continuing professional
      development course.
AB  - The Interpretive Visualization (IVIS) Group at the Division of Biomedical
      Communications, Dept. of Surgery, University of Toronto has developed a visually
      oriented, Internet-based Continuing Professional Development (CPD) course on
      Sentinel Node Biopsy. The site design methodology involved an extensive needs
      assessment, iterative formative evaluations of site and media design, a summative
      evaluation of the project, and a final evaluation for certification. Special
      emphasis was placed on asynchronous Web-based evaluation of the visual media
      including still images, animations, and interactive figures-used in the course.
      Results reinforced the importance of: needs assessment; a user-centered design
      process; and rapid prototyping.

PMID- 15164570
TI  - Colored pencil for medical and veterinary art.
AB  - Colored pencil is versatile in its use in both medical and veterinary
      illustration for the depiction of a variety of representational textures and
      tissues. The suggestion of tone and color can be created in linear strokes with a
      series of lines and cross hatching marks or created in paintery fashion through
      color layering and burnishing techniques. It also is an attractive compliment to
      mixed media including computer generated illustration.

PMID- 15164572
TI  - The history of Werner Spalteholz's Handatlas der Anatomie des Menschen. 1999.

PMID- 15164571
TI  - Improving parents' early recognition and understanding of infant cranial
      abnormalities through Web-based 2-D animations of 3-D structures.
AB  - A prototype Web site, "HeadStart: a craniosynostosis and positional plagiocephaly
      resource," was developed to help parents of children with cranial abnormalities
      access information about their child's condition. An on-line survey of 30 parents
      confirmed the need for information regarding the early diagnosis and treatment of
      cranial abnormalities. Three methods of creating the illusion of 3-D in a 2-D
      interactive animation were investigated. The final prototype Web site was
      developed using a novel approach to rendering 3-D models for use on the Web using
      a non-photorealistic rendering technique which emulated a hand-drawn appearance.
      Many advantages were found when creating 2-D animations based on 3-D files. A
      formative evaluation with parents revealed that the 3-D feature added to their
      understanding of cranial structures and led to a more complete understanding of
      their child's condition. Although the small sample size limits the ability to
      generalize about the success of including 3-D elements in educational programs,
      the research demonstrated that involving parents in the development process was
      successful in prioritizing the program content to fit with their needs.

PMID- 15164573
TI  - Can the nursing pipeline meet Tennessee's demand or nurses?

PMID- 15164574
TI  - Disease management.

PMID- 15164575
TI  - Preventing meeting burn-out: how to make the most of every meeting minute.

PMID- 15164576
TI  - [Diagnosing the mild cognitive impairment stage of Alzheimer's disease].
AB  - Recently, it has become important to diagnose Alzheimer's Disease (AD) at an
      early stage due to the development of AD therapy. Also, there is increasing
      recognition of a class of elderly people with complaints of memory loss but who
      nevertheless do not meet the criteria for dementia. "Mild cognitive impairment"
      (MCI) is the term used for this disorder, and amnestic MCI is highly converted to
      AD. In this study we evaluated the accuracy of diagnosis of amnestic MCI by
      cerebrospinal fluid total-tau protein (CSF/total-tau), cerebrospinal fluid
      amyloid beta 1-42 protein (CSF/A beta 1-42), and cerebral blood flow in the
      posterior cingulate cortex using SPECT. CSF/total-tau was the most appropriate to
      discriminate between normal cognitive individuals and those with amnestic MCI. We
      also evaluated the CSF/total-tau and MRI images between patients with stable MCI
      and those with progressive MCI, including those who converted to AD in the
      following two years. The stable type was characterized by normal CSF/total-tau
      levels and relatively high grade periventricular white matter lesions (PWML).
      Conversely, the progressive type was characterized by high CSF-tau levels and
      relatively low grade PWML. We speculate that stable MCI is due to ischemic change
      with in the white matter lesion, while progressive MCI may represent a previous
      stage of AD.

PMID- 15164577
TI  - [Capgras syndrome and possible worlds or places where the real person and its
      imposter coexist].
AB  - In a previous paper, the author has argued that what actually changes in the
      person whom the Capgras patient has chosen as his/her target of delusion is non
      attribute <I> such as having only "haecceity." At the same time, the author has
      pointed out that such ever-identical <I> is also the target of the indication for
      the rigid designator as proposed by S. Kripke. Such problems with indication and
      identity, however, are closely associated with ontology presented by possible
      worlds semantics, an analytic philosophy that was much debated during the latter
      half of the 20th century. The purpose of this paper is to try to define the
      essence of Capgras syndrome from the viewpoint of possible worlds semantics. If
      Capgras syndrome is taken as suggested by the patient's statement that "a real
      person has been replaced by an imposter," it is though that this statement refers
      to metaphysics with regard to the number of individuals who exist in the world.
      This is because the appearance of the imposter means the generation of a new
      individual who had not been in existence until that time. The creation of the new
      individual not only demands the existence of plural worlds as addressed by
      possible worlds semantics, but also provides a clue to solving problems with
      places where the real person and its imposter exist. If the number of individuals
      existing in the world is taken into account, it is difficult to spatio-temporally
      comprehend the places in which the real person and its imposter exist.
      Inevitably, the real person and its imposter have to be in mutually different
      possible worlds as defined by possible worlds semantics. This leads into the
      conclusion that after the onset of Capgras syndrome, the patient and the imposter
      are in a possible world that is different from the possible world to which the
      real person belongs. In the case presented herein, the patient repeatedly talked
      about how difficult it was to get access to the real person. If the patient was
      separated by space and time from the real person, his difficulty in getting
      access should have been only a matter of relativity. On the contrary, it is quite
      likely that what the patient really wanted to express is the fundamental
      impossibility of access that exists between two individuals who belong to
      mutually different possible worlds.

PMID- 15164579
TI  - [Changing the disease name for schizophrenia in Japan].

PMID- 15164578
TI  - [Discussion on diagnostic criteria for narcissistic personality disorder:
      Narcissism of conductor, von Karajan].

PMID- 15164580
TI  - [Change in the disease name for schizophrenia in Japan and its effect on informed
      consent given by physicians].

PMID- 15164581
TI  - [Influence of changing the disease name for schizophrenia on clinical practice of
      psychiatry in community psychiatric hospitals in Japan].

PMID- 15164582
TI  - [Medical, practical and sociocultural significance in changing the disease name
      for schizophrenia in Japan].

PMID- 15164583
TI  - [Influence of changing the disease name for schizophrenia on Japanese patients'
      quality of life ].

PMID- 15164584
TI  - [Process and future tasks in changing the disease name for schizophrenia in
      Japan].

PMID- 15164585
TI  - [Significance of atypical psychoses in present-day psychiatry].

PMID- 15164586
TI  - [Concepts in atypical psychoses].

PMID- 15164587
TI  - [Psychopathological study on atypical psychoses].

PMID- 15164588
TI  - [Biological study on atypical psychoses].

PMID- 15164589
TI  - [Outcome of genetic studies on atypical psychoses].

PMID- 15164590
TI  - [Influence of rearing environment on development of the human brain].

PMID- 15164591
TI  - [Mechanism of the brain's adaptation to stress].
AB  - To clarify the mechanism of adaptation to stress in the brain, we performed
      neuroimaging studies by functional magnetic resonance imaging and
      magnetoencephalography. First, to investigate which areas of the brain play an
      important role in the perception of stressful events, we performed fMRI for
      recognition of unpleasant words concerning interpersonal relationships. Secondly,
      we evaluated the effect of various stresses on the sensory gating system by MEG
      to show whether stress could affect the brain mechanism. Finally, we studied the
      neural activity associated with the expectancy of emotional stimuli using fMRI
      and MEG, because of the importance of expectancy in adaptation to stress. Our
      results suggested that stressful events might be recognized in the same brain
      regions, that acute stress might affect one brain mechanism, and that expectancy
      might suppress incoming stressful stimuli.

PMID- 15164592
TI  - [Hypothetical theory on the etiology of neurodevelopmental disorders].

PMID- 15164593
TI  - [Circadian-rhythm sleep disorders].

PMID- 15164594
TI  - [Relation between benign prostatic hyperplasia and obesity and estrogen].
AB  - PURPOSE: There have been few reports on correlations between resection volume of
      benign prostatic hyperplasia, body mass index (BMI) and estrogen. This study was
      undertaken to evaluate the correlations. METHOD: In this study, we considered 50
      patients who had benign prostatic hyperplasia (BPH) and underwent suprapubic
      prostatectomy (SPP). Men with prostate cancer or prior prostate surgery were
      excluded. The relationship between prostate resection volume and BMI was
      examined. Additionally, patients were divided into two groups according to BMI:
      less than 25, and more than 25. The two groups were evaluated according to
      stained estrogen receptors. RESULTS: BMI was correlated positively with prostate
      volume (p < 0.01). However, positive rates of estrogen receptors showed no
      significant difference between the two groups. CONCLUSIONS: This was a study
      describing the relationship between BMI and prostate volume. Obesity has been
      hypothesized to be associated with BPH because of the endocrine changes in men
      that occur with age, including increased estrogen and decreased testosterone. Our
      findings suggest that estrogen may play a pathophysiologic role in benign
      prostatic hyperplasia. Further studies of large populations are needed to
      validate this assumption.

PMID- 15164595
TI  - [Investigation for clinical practice of pulmonary function tests in undergraduate
      medical education--results from the inquiries to 91 medical institutes with the
      Department of Laboratory Medicines in Japan].
AB  - Pulmonary function tests(PFTs), especially spirometry, play important roles in
      screening and diagnosing the patients with bronchial asthma or chronic
      obstructive pulmonary disease. It is reported, however, that only 38% of the
      general physicians utilizes spirometry. Based on the assumption that clinical
      practices might be insufficient to learn PFTs in the undergraduate education
      periods, we made inquiries to 91 institutes with the departments of laboratory
      medicine in April 2003. The reply was from 67 institutes(73.6%). In 57
      institutes(85.1%) they prepared a clinical practice curriculum for the students.
      The periods for the practice were 1 week in 38 institutes(56.7%) and 2 weeks in
      10(17.5%). In 36 institutes(76.6%). In 47 institutes in which physiological
      examinations were included in the curriculum, PFTs were performed as one of the
      clinical practices. In all the institutes they employed either spirometry or flow
      volume curve test. In 20 institutes(55.6%), approximately 2 hrs were assigned to
      the practice of PFTs. In 24 institutes (66.7%), the clinical technologists
      participated in educating the students. The main reasons why they did not employ
      PFTs in the practice were shortness of teaching staffs(7 institutes, 22.6%) or
      practicing time(4 institutes, 12.9%). These inquiries prevailed that practices of
      PFTs were performed mainly by lecture or by observation, since the practice time
      was insufficient to learn several kinds of PFTs. The Japanese Society of
      Laboratory Medicine should immediately prepare and popularize a model core
      curriculum for the practice of PFTs.

PMID- 15164596
TI  - [Nutrition assessment protein].
AB  - Nutrition status must be estimated during a patient's hospitalization. Body
      weight, hemoglobin or serum albumin are used to estimate nutrition status, but
      they can not reflect the present nutrition status. Recently, rapid turnover
      protein(RTP) has been proposed as a nutrition assessment protein, reflecting real
      time nutrition status. The halves in the serum of retinal-binding protein(RBP)
      and transthyretin (TTR) are 0.5 and 2 days, respectively. Their physiological
      variations, such as intra-individual, diet, and athletics, are within 10%, so
      they are suitable for monitoring present nutrition status. Because they are
      negative acute-phase reactants, we have to measure CRP as a marker for the acute
      phase reaction. Measuring RBP and TTR as monitoring markers reveals the accurate,
      real-time nutrition status of the patient. Providing accurate information for a
      patient's nutrition situation will support cure and early discharge, and reduce
      medical costs.

PMID- 15164597
TI  - Postgraduate education in laboratory medicine and certification/re-certification
      of clinical pathologists in Taiwan.
AB  - The Taiwan Society of Clinical Pathologists (TSCP) plays a central role in
      postgraduate education of laboratory medicine and the certification/re
      certification of clinical pathologists in Taiwan. For the certification of
      clinical pathologists, TSCP establishes "Guidelines and Scope of Resident
      Training" and "Standards for Training Hospitals in Clinical Pathology(CP)",
      administers board examinations, and issues board certifications/re
      certifications. There are two types of CP resident training programs, including a
      straight CP program with 3 years of CP training for a CP certificate and a
      combined program with 3 years of Anatomic Pathology training and 2 years of CP
      training for both the CP and AP certificates. The core curriculum for CP training
      includes: (1) Clinical Chemistry (at least 4 months), (2) Clinical Microscope
      with Parasitology (at least 3 months), (3) Clinical Hematology (at least 4
      months), and (4) Clinical Microbiology with Clinical Virology (at least 4
      months), (5) Immunohematology and Blood Banking (Transfusion Medicine) (at least
      3 months), (6) Clinical Serology and Immunology(at least 4 months), and (7)
      Laboratory Management (at least 2 months). The curriculum for third-year training
      is not specified and may be in any field. In recent years, the board examination
      has emphasized the topics of Molecular Biology and Laboratory Informatics. The
      TSCP has also established an accreditation and inspection program for the CP
      resident raining hospitals. Each accredited CP training hospital is required to
      have a detailed teaching protocol of CP training. Quotas are assigned according
      to the available CPs of the accredited hospitals. The accreditation period is 3
      years. Through sponsoring scientific and educational programs, the TSCP offers
      credit hours of education in laboratory medicine, which are required for re
      certification of CPs in Taiwan. The members of the TSCP meet at least twice a
      year for scientific presentations and seminars. In addition, two to four
      symposia, offering 8 credit hours each, are held each year in various
      subspecialties of CP. In 2003, 22 hospitals were accredited as CP training
      hospitals for a total quota of 26. Until 2003, the TSCP had certified 116 CPs. At
      the present time, only 103 certified CPs are actively practicing laboratory
      medicine. Re-certification requires 100 credit hours of continuing education. The
      requirements for board certification and re-certification are the two main
      driving forces for CPs in Taiwan to seek continuing education. Our model of
      education for CPs has proven to be effective. The number of practicing CPs
      increased from 21 (one per 3,083 beds) in 1991 to 103 (one per 929 beds) in 2002.
      Most of the CPs are associated with medical centers(62/103, 60.2%) and regional
      hospitals(38/103, 36.9%).

PMID- 15164598
TI  - Education and certification of laboratory medicine.
AB  - Not only are there differences in the definition of a specialist, but there are
      also different education systems for residents and certifications of specialists
      of laboratory medicine from country to country. The resident education program,
      the certification system of specialists of laboratory medicine, requirements for
      specialist examination, requirements for training hospitals, and the quota system
      for resident distribution in Korea are reported here for comparison with other
      countries' systems. Also, the function of a specialist society for laboratory
      medicine is described, to demonstrate its profound involvement in the education
      and certification of laboratory medicine.

PMID- 15164599
TI  - [Clinical usefulness of urinary diacetylpolyamines as novel tumor markers].
AB  - N1,N12-Diacetylspermine(DiAcSpm) and N1,N8-diacetylspermidine(DiAcSpd) are
      excreted in the urine of healthy persons as minor components of urinary
      polyamine, with small individual variations in amount. They are promising tumor
      markers, since their excretion is frequently elevated in patients with various
      types of cancers. DiAcSpm is sensitive in cancer detection, while DiAcSpd is
      highly specific for cancer. Diacetylpolyamines were initially characterized and
      determined by HPLC fractionation, followed by enzymatic detection. More recently,
      antibodies highly specific for DiAcSpm and DiAcSpd were developed, and an ELISA
      system applicable to the determination of urinary DiAcSpm was established.
      Measurement of urinary DiAcSpm using this ELISA system revealed that DiAcSpm is a
      more sensitive tumor marker than CEA, CA19-9 and CA15-3 for colon and breast
      cancers. More importantly, DiAcSpm efficiently detects patients at early stages.
      On the other hand, CEA, CA19-9 and CA15-3 are quite insensitive for early stage
      cancers. The urinary DiAcSpm level tends to remain low even in tumor-bearing
      individuals when their cancerous lesions remain static, while it rises rapidly
      concomitant with recurrence. DiAcSpm may serve as a prognostic indicator and
      marker for recurrence of prostate and colon cancers. Diacetylpolyamines may turn
      out to be general tumor markers, since active proliferation of any cancer tissues
      would likely be accompanied by activation of polyamine metabolism.

PMID- 15164600
TI  - [Establishment of an ELISA system of N1,N12-diacetylspermine in human urine].
AB  - OBJECTIVE: It is known that two kinds of Diacetylpolyamine, N1,N12
      Diacetylspermine(DiAcSpm) and N1,N8-Diacetylspermidine(DiAcSpd), are excreted in
      urine. Although these two substances are 0.4% and 1.2% of the whole polyamine,
      respectively, these substances may be important for a sick diagnosis. The aim of
      this study was to develop a sensitive and specific method for detecting DiAcSpm.
      METHODS: We developed a new competitive ELISA system for the measurement of
      DiAcSpm in human urine, using polyclonal antibodies against DiAcSpm. RESULTS: The
      lower limit of detection of this ELISA was 4.53 nM/assay. The higher limit of
      detection was 145 nM/assay. Mean recovery was 101% (range, 96.3-108%). The
      coefficients of variation (CV) for within-run measurements by this method were
      4.87% (mean = 95.5 nM) and 5.20% (mean = 32.4 nM), and the between-run CV were
      7.53% (mean = 101 nM) and 9.46% (mean = 33.8 nM). CONCLUSIONS: We have
      established an ELISA system for the quantification of urinary DiAcSpm that uses
      novel polyclonal antibodies. Our ELISA system is simple and sensitive.

PMID- 15164601
TI  - [The significance of urine di-acetyl spermine level as a cancer marker for
      colorectal cancer].
AB  - We analyzed the significance of the measurement of urine di-acetyl spermine
      (DiAcSpm) as a cancer marker for colorectal cancer treatment. We measured both
      the urine DiAcSpm(ELISA, normal range: 0-0.25 mumol/creatinine) and serum CEA
      (normal range: 0-5.0 ng/ml) of preoperative and postoperative colorectal cancer
      patients every month. We compared the positive rate from the cancer stage and the
      power of prognostic prediction. We divided the colorectal cancer patients into 4
      groups: Group A: both levels were high; Group B: only the CEA level was high;
      Group C: only the DiAcSpm level was high; Group D: both levels were within a
      normal range. The positive rates of DiAcSpm and CEA from cancer staging were as
      follows: Stage 0: 62% and 9.5%, Stage I: 60% and 10%, Stage II: 70% and 42%,
      Stage III: 82% and 47%, and Stage IV: 88% and 63%, respectively. There was a
      significant difference (p < 0.0001) between both levels, especially for early
      stage cases. The two-year survival rate was 0% in Group A, 100% in Group B, 72.7%
      in Group C and 100% in Group D. The difference among the 4 groups was significant
      (p < 0.0001). This showed that urine DiAcSpm predicted the prognosis after
      colorectal cancer surgery more exactly than serum CEA.

PMID- 15164602
TI  - [Urine diacetylspermine as a novel tumor marker for pancreatobiliary carcinomas].
AB  - A novel urine tumor marker, diacetylspermine, was compared with two conventional
      serum tumor markers, carcinoembryonic antigen (CEA) (highly specific for
      pancreatic cancer) and carbohydrate antigen (CA) 19-9 (highly sensitive for
      pancreatic cancer), in 125 patients with bilio-pancreatic tumors. When the
      diagnoses of benign or malignant conditions were examined, the sensitivity of
      urine diacetylspermine (75%) was shown to be higher than that of CEA (44%; P =
      0.044) and CA19-9 (75%). The specificity of urine diacetylspermine (81%) was
      lower than that of CEA (92%) and as high as that of CA19-9 (80%). These results
      suggest that urine discetylspermine is a highly sensitive and specific novel
      marker for bilio-pancreatic carcinoma.

PMID- 15164603
TI  - [Tissue factor expression at the site of inflammation: a cross-talk between
      inflammation and the blood coagulation system].
AB  - Recent studies have revealed a close association of the blood coagulation system
      with inflammation and immune reactions. The products of the cascade reaction of
      blood coagulation can work as inflammatory mediators or immune modulators, and,
      vice versa, some inflammatory or immune stimuli are linked to induction of blood
      coagulation. First, tissue factor (the blood coagulation initiator), the
      monocyte/macrophage tissue factor expression regulatory factors associated with
      inflammation and immune reactions, and the assembly of coagulation factors on
      leukocytes were reviewed. Second, evidence of leukocyte tissue factor expression
      and subsequent fibrin deposition were demonstrated at sites of infection or
      allergic reactions, using immunohistochemical staining. Third, the progress in
      the investigation of thrombin was reviewed from the viewpoint of its effects on
      inflammation (vascular permeability enhancement, leukocyte chemotaxis, chemical
      mediator release, etc.) and immune reactions (T-cell proliferation, cytokine
      production, etc.). The evidence presented here indicates a cross-talk between
      blood coagulation and inflammatory and immune reactions, suggesting that the
      products of the clotting reaction (e.g., thrombin) in lesions are real-time
      markers of inflammatory diseases.

PMID- 15164604
TI  - [Evaluation of thrombin in urine as a real-time indicator of clotting activation
      in glomerulonephritis].
AB  - When tissues are injured and bleeding occurs, blood clotting is immediately
      activated and fibrin clots are formed by thrombin. Afterwards, antithrombin III
      promptly inactivates thrombin, which restricts the clotting to the bleeding site.
      In inflamed sites, tissue factor is expressed on cells in the lesion by
      stimulation from cytokines, and produces thrombin. In this case, thrombin may
      survive longer because of inefficient inactivation by antithrombin III due to
      dilution and less perturbation in the interstitial fluid, and therefore, has a
      greater chance to activate thrombin receptors (protease-activated receptors:
      PARs) on the cells, which induces various cellular events including
      proliferation, migration, and shape change. Recent studies have suggested a
      pathophysiological association of the PAR pathway with crescentic
      glomerulonephritis. However, the role of thrombin in human diseases has not been
      fully studied, probably because of a lack of simple and reliable methods for
      measuring thrombin in clinical samples. To solve this problem, we developed an
      ELISA system for human alpha-thrombin and applied it to the measurement of
      thrombin in the urine of patients with glomerulonephritis. Thrombin in urine was
      detected in glomerulonephritic patients but not in healthy volunteers or
      disseminated intravascular coagulation patients, which suggests that thrombin in
      urine may reflect thrombin generation by clotting activation in the glomerular
      lesion.

PMID- 15164605
TI  - [A novel molecular marker for thrombus formation and life prognosis--clinical
      usefulness of measurement of soluble fibrin monomer-fibrinogen complex (SF)].
AB  - For a long time fibrinopeptide A(FPA), fibrinopeptide B(FPB), D-dimer, FM test,
      serum FDP, and thrombin anti-thrombin complex(TAT) are being used as molecular
      markers to for sure diagnose hypercoagulable state and thrombus formation. Indeed
      these molecular markers are very useful for diagnosing thrombus formation,
      disseminated intravascular coagulation(DIC), and the indicator of treatment of
      DIC. But these molecular parameters are not enough and difficult for prognosis of
      the disease or predicting the complication of patients as the most important
      subject for clinicians. The soluble fibrin monomer-fibrinogen complex (SF) is a
      complex coupling fibrin monomer and fibrinogen molecules to be formed in the
      early-activated state of blood coagulation. Thus such a molecular complex is
      expected to serve as a parameter for the diagnosis of thrombus formation and DIC,
      in particular its early stage. The aim of the present study is to evaluate a
      potential usefulness of a newly developed SF test utilizing an SF specific
      monoclonal antibody (IF-43). We measured SF together with established other
      parameters in 195 patients with DIC, subclinical DIC/hypercoagulable state, and
      non-DIC. The diagnosis of DIC was made based on a modified version of the
      criteria established by the Ministry of Health, Labor and Welfare of Japan.
      Underlying disease includes leukemia, malignant lymphoma, myelodysplastic
      syndrome (MDS), multiple injury, giant ovarian tumor, prostatic cancer with
      multiple bone metastasis, lung cancer, breast cancer with multiple lung and bone
      metastasis, severe pneumoniae, sepsis, hemophagocytic syndrome (HPS), and
      rheumatoid arthritis. The SF levels in DIC patients were significantly higher
      than those in the subclinical DIC/hypercoagulable state, and the non-DIC
      patients. Receiver operating characteristic (ROC) analysis shows that the
      specificity and sensitivity of the SF assay appears to be satisfactory. As the
      level of SF reflects the thrombin generation activity in plasma, it would serve
      as a strong tool to selectively kick up the state of thrombin generation. These
      results indicate that the SF could be a specific and reliable parameter for the
      diagnosis of DIC and contribute to legitimate managements of patients with DIC.
      The excessive life response to serious clinical insults, such as sepsis, severe
      pancreatitis, trauma and shock, is called systemic inflammatory response syndrome
      (SIRS). Once SIRS occurs, people may often die from serious complications such as
      adult respiratory distress syndrome (ARDS), acute lung injury (ALI), disseminated
      intravascular coagulation (DIC) and multiple organ failure (MOF). Especially, ALI
      followed by pneumoniae associated with SIRS could depend on patient's prognosis
      and life. That is to say, it seems to be urgent for clinicians to make
      differential diagnosis between Pneumoniae associated with SIRS and Coagulopathy
      (PASC) and Simple Pneumoniae (SP). Soluble fibrin monomer-fibrinogen complex(SF)
      is formed in the early-activated state of blood coagulation. Thus such a
      molecular complex is expected to serve as a parameter for the diagnosis of
      coagulopathy, in particular its early stage. The aim of the present study is to
      make differential diagnosis between Pneumoniae associated with SIRS and
      Coagulopathy (PASC) and Simple Pneumoniae(SP) by using a newly developed SF test
      utilizing an SF specific monoclonal antibody (IF-43). We measured SF together
      with established other parameters, hemogram, blood laboratory items in 7 patients
      with PASC and 17 patients with SP. The diagnosis of Pneumoniae was defined
      according to the criteria: clinical symptoms abnormal shadow in both Chest X-p
      and Chest CT, increased level of CRP, number of WBC. The diagnosis of SIRS was
      based on the criteria established by American College of Chest Physicians
      (ACCP)/Society of Critical Care Medicine (SCCM) Consensus Conference held in
      August of 1991 in Northbrook, IL (USA). Underlying disease includes leukemias,
      malignant lymphoma, myelodysplastic syndrome (MDS), multiple myeloma, idiopathic
      thrombocytopenia purpura(ITP), multiple injury (bone fracture), cerebral
      hemorrhage, enterocolitis, Appendicitis, lung cancer, larynx cancer,
      bronchiolitis obliterans organizing pneumonia(BOOP), chronic obstructive
      pulmonary disease(COPD), sepsis. The SF levels in PASC patients are significantly
      higher than those in SP patients (p < 0.001). Otherwise, there is no significant
      difference of the CRP levels between in PASC group and SP group (p < ns). There
      is no co-relationship between SF level and D-dimer level. Receiver operating
      characteristic (ROC) analysis shows that the specificity and sensitivity of the
      SF assay appears to be quite satisfactory. As the level of SF reflects the
      thrombin generation activity in plasma, it would serve as a strong tool to
      selectively kick up the state of thrombin generation. These results indicate that
      the SF could be a specific and reliable parameter for the diagnosis of PASC and
      contribute to legitimate managements of patients with PASC.

PMID- 15164606
TI  - [New molecular marker in dialysis setting--misfolded beta 2-microglobulin].
AB  - More than 25 clinical settings in amyloidosis have been acknowledged in which a
      peculiar criminal protein, a precursor protein, has been identified. As of now,
      however, the mechanism of amyloidogenesis, by which a precursor protein is
      transformed irreversibly into an amyloid protein, remains to be clarified. We
      speculated that a study of the molecular conformation of beta 2-microglobulin
      (beta 2 m), a precursor protein in dialysis-related amyloidosis (DRA), might
      provide a typic model of amyloidogenesis in other precursor proteins. Therefore,
      we investigated the misfolding of beta 2 m in DRA using a specific monoclonal
      antibody against C-terminal peptide 92-99 of beta 2 m. Our study indicated the
      possibility that the monoclonal antibody specific for C-terminal 92-99 of beta 2
      m can detect a pre-amyloid state in amyloidogenesis in vivo, which might take
      place in the extravascular space.

PMID- 15164607
TI  - [Tumor markers of urinary tract carcinoma].
AB  - The tumor markers for malignant tumors arisen from urinary system including
      prostate cancer were reviewed. As for renal cell carcinoma there was no good
      marker used in routine test level at present. In the diagnosis of urothelial
      (transitional cell) carcinoma, mainly bladder cancer, 3 methods (urinary BTA,
      NMP22 and BFP) are used now in Japan. They all seem to be not fully sufficient in
      respect of the specificity. In foreign countries, new tests such as urinary
      telomerase and BLCA-4 are used and have been evaluated. On the diagnosis of
      prostate cancer, serum total PSA is well established and used. Various PSA
      relation markers have been advocated for the differentiation between benign
      prostate hypertrophy and carcinoma in so called "gray zone" level of total PSA.
      In methods based on the molecular forms of PSA, the ratio of free PSA to total
      PSA (f/T) is widely use, and proPSA is a test that is expected. Other approaches
      such as volume of index PSA, age specific PSA reference range and PSA velocity
      are also in practical application. Human glandular kallikrein 2, which belong to
      the human kallikrein family as well as PSA, is expected as a tumor specific
      marker.

PMID- 15164608
TI  - Regulation of dopamine and MPP+ transport by catecholamine transporters.
AB  - Following exocytotic release of the biogenic amine neurotransmitters,
      norepinephrine and dopamine, are removed from the synaptic cleft by the
      respective transporter, norepinephrine transporter (NET) and dopamine transporter
      (DAT) located on the plasma membrane. The catecholamine transporters are the
      molecular targets for psychoactive drugs as well as drugs of abuse such as
      cocaine and amphetamine and the Parkinsonism-inducing neurotoxin, MPP+. Nicotine
      regulates the transport of catecholamines and MPP+ and may exert self-medicating
      effects for depression, schizophrenia and attention deficit hyperactivity
      disorder, and neuroprotective effects against MPP+ through the regulation of the
      transporters. The availability of cDNAs of these transporters has permitted
      detailed pharmacological studies in heterologous expression systems for
      determining the mechanisms of action of nicotine on transporters. Moreover,
      functional analysis of the effect of single amino acid substitution suggests that
      specific residues in DAT molecules may play a significant role in interaction
      with MPP+ and cocaine, and thus would promise a development of novel drugs with
      diverse chemical structures.

PMID- 15164609
TI  - [Calcium signaling mediated by nicotine receptors in neurons].
AB  - Nicotine has many acute and chronic pharmacological effects. Nicotine treatment
      activates neuronal nicotinic acetylcholine receptors (nAChR) in peripheral and
      central nervous systems leading to depolarization and elevation of intracellular
      calcium levels, which are considered to cause stimulation of neurotransmitter
      release, synaptic transmission, intracellular signal transduction and gene
      expression. Multiple subtypes of nAChRs display different sensitivity to
      nicotinic agonists and antagonists. Each of these subtypes has a unique
      distribution in peripheral and central nervous systems. Although presynaptic
      nAChRs have been extensively studied to modulate the release of
      neurotransmitters, the functional importance of nAChRs in somata is not
      sufficiently characterized. To clarify the mechanisms of calcium signaling and
      its stimulation of gene expression via nAChRs in somata, we have investigated
      nAChR-mediating calcium signaling mechanisms including phosphorylation of p42/44
      MAP kinase (ERK), CREB and Akt in PC12h cells. Nicotine transiently activates
      phosphorylation of ERK-, CREB and Akt. Nicotine induces the activation of both
      PI3 kinase/Act and ERK/CREB pathways via common pathways including non-alpha 7
      nAChRs, L-type VSCC, CaM kinase and EGFR in PC12h cells, but Src family tyrosine
      kinases only participate in the pathway to activate Akt. Based on these results,
      we discuss nAChR signaling mechanisms in neurons.

PMID- 15164610
TI  - [Neuropsychopharmacological profile of nicotine].
AB  - The reinforcing effects of nicotine have been investigated by intravenous self
      administration methods using mice, rats, dogs, squirrel monkeys, rhesus monkeys,
      baboons, and humans. Based on accumulated data related to these effects, it is
      clear that subjects show moderate self-administration of nicotine with no marked
      manifestation in contrast to excessive self-administration of cocaine with
      hyperactivity and of morphine with withdrawal syndrome. The magnitude of
      reinforcing effects of nicotine was judged to be lower than that of cocaine and
      other abused drugs by the progressive ratio schedule method although persistent
      self-administration behavior for nicotine was maintained under the second-order
      schedule with conditioned stimulus in monkeys. The brain mechanism producing the
      reinforcing effects of nicotine is considered to involve nicotinic receptors at
      the nucleus accumbens, prefrontal cortex or other regions, as well as the
      mesolimbic dopaminergic system. It has been demonstrated by brain imaging
      techniques such as PET and fMRI that the relevant brain sites for producing
      craving for abused drugs such as cocaine include the amygdala, dorsolateral
      frontal cortex and anterior cingulated cortex. Further studies should elucidate
      the mechanism of craving for cigarettes by these imaging techniques. The actions
      of nicotine and its analogs have been studied for the purpose of developing
      therapeutic drugs for Alzheimer's disease, Parkinson's disease, Tourrette's
      syndrome and so on. Thus, studies on nicotine and its analogs with a wide variety
      of pharmacological profiles are interesting and important in the field of
      neuropsychopharmacology.

PMID- 15164611
TI  - [Studies on clinical characteristics of nicotine dependence using a two
      compartment model of drug dependence].
AB  - The purpose of the present study was to develop a new clinical evaluation form to
      compare the clinical characteristics of nicotine dependence with those associated
      with other drugs of abuse, using a two-compartment model consisting of "drug
      dependence" and "dependence syndrome". The evaluation form consisted of five
      scoring items: subjective effects, drug liking, withdrawal syndrome, acute
      psychic and acute physical disorders, and social disturbance. "Drug dependence"
      was defined by positive scores on the "drug liking" item. "Dependence syndrome"
      was defined by positive scores on drug-induced pathological symptoms (withdrawal
      syndrome, and acute psychic and physical disorders) and social disturbance. The
      subjects were dependent on nicotine (cigarette smoking) (n = 114), alcohol (n =
      101), methamphetamine (n = 90), inhalants (n = 63), and benzodiazepines (n = 39).
      All subjects met the DSM-IV-TR criteria for drug dependence. Nicotine produced a
      mild or the least degree of drug liking and withdrawal syndrome, without any
      significant social disturbance, or acute disorders. The other four drugs produced
      more intensive degrees of withdrawal syndrome and acute psychic and physical
      symptoms, with more significant social disturbance than nicotine. The present
      study indicated that nicotine dependence differed from other forms of drug
      dependence in that nicotine was not associated with "dependence syndrome".

PMID- 15164612
TI  - [Effect of smoking on pharmacokinetics of antipsychotics].
AB  - The population of Japanese smokers has decreased; however, the prevalence of
      smokers among psychiatric patients has been reported to be as high as 80% in
      schizophrenic patients. Although the impact of smoking on the pharmacokinetics of
      antipsychotics has been reported, results have been controversial. At first, the
      impact of smoking on plasma haloperidol (HAL) concentrations was investigated in
      Japanese male schizophrenic inpatients treated with HAL per os. Smokers had
      approximately 20% lower HAL concentrations/daily dose of HAL/kg body weight than
      non-smokers. The impact of genetic polymorphism of CYP1A2 that are related to the
      induction of the isozyme on the plasma levels of HAL in male smokers with
      schizophrenia was also investigated. A point mutation from C to A in intron 1 at
      position 734 and a point mutation from G to A at position--2964 in the 5'
      flanking region of CYP1A2 were identified by the PCR-RFLP method. Regarding C/A
      polymorphism in intron 1 at position 734, no significant difference was found in
      the plasma concentrations of HAL corrected for dose and weight among the subjects
      with A/A, A/C and C/C genotypes. Regarding G/A polymorphism at position--2964 in
      the 5'-flanking region, no significant difference was found in the plasma
      concentrations of HAL corrected for dose and weight between subjects with G/G and
      G/A.

PMID- 15164613
TI  - [Immunophilin ligands: from immunosuppressants to neuroprotective drugs].
AB  - Non-immunosuppressive immunophilin ligands (NI-IPLs) are attracting attention as
      new candidate drugs for neuroprotection and/or neurorestoration, particularly
      since they do not have the adverse effects of immunosuppressants. However, it is
      not yet enough to understand that NI-IPLs are useful drugs for treating
      neurological disorders. In particular, the molecular mechanism of NI-IPL activity
      in target cells in the brain remains obscure. In this review, we focused on the
      molecular basis of the neuroprotective properties of IPLs. Our findings suggest
      that IPLs have neuroprotective effects mediated by multiple beneficial properties
      such as a glutathione (GSH)-activating effect, a neurotrophic factor (NTF)
      activating effect, and an anti-apoptotic effect, but not by an immunosuppressive
      effect, both in cell cultures and in vivo. In particular, the GSH-activating
      effect and the NTF-activating effect of NI-IPLs may be essential to the
      expression of their neuroprotective properties. Thus, NI-IPLs might have a
      potentially beneficial effect by ameliorating neurological disorders, since they
      do not cause serious side effects such as immune deficiency.

PMID- 15164615
TI  - [Postherpetic neuralgia alleviated by an SSRI fluvoxamine: two cases of PHN
      accompanied with depression were treated with fluvoxamine].
AB  - Case 1: female, age 76. Fluvoxamine (50 mg/day) initiated a reduction of pain on
      the 14th day of administration and completely ameliorated pain as well as
      depression. Case 2: female, age 76. Fluvoxamine (25 mg/day) was administered with
      tandospirone (15 mg/day) which augments the effect of an SSRI. This combination
      regimen induced a reduction of PHN-pain on the 10th day and as the analgesic
      effect attained nearly 50%, there occurred a reflaming of pain on the 35th day.
      Increasing fluvoxamine to 50 mg/day reameliorated pain on the 49th day, and a
      further increase to 75 mg/day finally eliminated pain and depression at the end
      of the 3rd month. The long latency of fluvoxamine action, its shortening by
      tandospirone and the parallel changes of PHN and depression are all indicative of
      that the same mechanism, namely renormalization of the dysfunctioned central
      serotonergic transmission would be underlying both the anti-PHN and
      antidepressant actions. It would be concluded that fluvoxamine alleviates PHN by
      restoration of the descending serotonergic inhibition of primary afferent
      activity that carries pain impulses.

PMID- 15164614
TI  - [Clonazepam as a therapeutic adjunct to improve the management of depression].
AB  - Clonazepam, which is a benzodiazepine structurally related to chlordiazepoxide
      hydrochloride, diazepam and nitrazepam, has been available for the treatment of
      seizure disorders in the USA since 1976 and in Japan since 1981. Increasingly,
      clonazepam has been used in the treatment of a variety of psychiatric disorders.
      The effect of clonazepam on depression was first reported by Jones and Chouinard
      in 1985. Since their report, many investigators have reported on the
      antidepressive properties of clonazepam. A daily dose of at least 3.0 mg
      clonazepam in augmentation of ongoing antidepressant treatment should be
      considered in depression. Regarding clonazepam augmentation therapy, if a patient
      does not show improvement by the end of four weeks, the treatment regimen should
      be altered. Age at onset of the first depressive episode and a history of family
      psychiatric illness should be considered the predictor of prognosis. The author
      discusses specific guidelines for the use of clonazepam in depression.

PMID- 15164616
TI  - [Effects of neurotensin microinjected into ventral tegmental area on spontaneous
      motor activity in neonatal 6-hydroxydopamine-treated rats].
AB  - Intracerebroventricular treatment of the catecholamine neurotoxin, 6
      hydroxydopamine (6-OHDA) after desmethylimipramine pretreatment results in
      semipermanent brain dopamine (DA) depletion. It has been shown that rats
      neonatally treated with 6-OHDA show hyperactivity in an open-field test. The
      purpose of this study was to investigate the spontaneous motor activity in
      neonatal 6-OHDA-treated rats following bilateral saline (SAL; 0.25 microliter) or
      neurotensin (NT; 1.25, 2.50, 5.00 micrograms/0.25 microliter/side) microinjection
      into the ventral tegmental area. Each dose of NT significantly augmented
      locomotor activity in 6-OHDA-treated rats. On the other hand, controls did not
      show significant increase in lower dose of NT. Effect of NT microinjection on
      number of rearings in the 6-OHDA-treated group was not significantly altered
      compared to the vehicle-treated group. These results suggest that the responses
      in locomotor activity to NT the ventral tegmental area increase in neonatal 6
      OHDA-treated rats, and imply that residual activity in mesolimbic DA neurons
      which is mediated by NT receptors contributes to a part of the hyperactivity seen
      after neonatal 6-OHDA lesion.

PMID- 15164617
TI  - [DISC1 and schizophrenia].
AB  - Molecular mechanisms underlying the pathogenesis of schizophrenia remains
      elusive. The difficulty in accessing the mechanisms stems from, at least in part,
      multiple etiologies for schizophrenia. We have studied DISC1, as it was
      identified as a candidate gene for a schizophrenia-associated mental condition
      with the single etiology. Thus far, we have obtained evidence that DISC1 may have
      implications in neurodevelopment. This concept fits with many historical
      observations found for schizophrenia in association with neurodevelopmental
      abnormalities. DISC1 may become one of the key molecules in studying the
      pathogenesis of schizophrenia.

PMID- 15164618
TI  - [Dysfunction of serotonergic systems in thiamine-deficient diet fed mice: effects
      of SSRI on abnormality induced by thiamine deficiency].
AB  - Mice fed a thiamine deficient (TD) diet, showed some abnormal behaviors such as
      amnesia and mood abnormality. It is known that several neurons, especially marked
      in serotonergic neuron, are damaged in humans and rodents in the earlier phase of
      TD. The symptoms derived from dysfunction of serotonergic neurons are observed in
      Wernicke-Korsakoff patients (WKS)-derived TD, and it is known that fluvoxamine is
      effective for WKS. However, the mechanism of this dysfunction is still unclear.
      For that reason, we studied the relative mechanism between abnormal behaviors and
      selective dysfunction of serotonergic neurons in TD animals. As a result, this
      dysfunction by TD is much affected by the brainstem region. But the effect of
      fluvoxamine on depressive symptoms in WKS patients is not reported; therefore we
      also studied the effects of fluvoxamine on the depressive behaviors in TD mice as
      a model of WKS. The increase of immobility time in a forced swimming test as
      depressive behavior in TD mice was significantly inhibited by fluvoxamine,
      suggesting an improvable effect on depressive symptoms. With those results of
      ours, the possible mechanisms between the abnormal behaviors derived from the
      dysfunction of serotonergic neurons and the role of serotonin in TD and WKS are
      reviewed here.

PMID- 15164619
TI  - Molecular cloning, expression and purification of protein 2A of hepatitis A
      virus.
AB  - Expression of the protein 2A of Hepatitis A virus (HAV), spanning amino acids 764
      through 981 of the viral polyprotein results in a strong inhibition of cap
      dependent translation (Maltese et al., 2000). However, the molecular mechanism
      responsible has remained unclear, in part because the HAV 2A protein was not
      available in amounts large enough to allow biological or structural studies. To
      address this issue, a cDNA representation of the sequences encoding HAV 2A was
      generated by PCR, using primers that introduced an AUG triplet, and a sequence
      coding for 6 histidine residues at the 5'- and 3'-termini of the genomic
      sequence, respectively. The cDNA fragment was introduced by cassette exchange in
      the inducible expression vector pQE-60, and the construct was propagated in
      bacteria E. coli M15 which constitutively expresses the lac repressor. Upon
      induction with IPTG (1 mM), HAV 2A was visualized by SDS-PAGE of bacterial
      lysates as a prominent band M(r) = 21 kDa. The identity of the polypeptide was
      confirmed by both MALDI-TOF peptide mapping and direct amino acid sequencing. The
      His-tagged HAV 2A was extracted from bacterial pellets under totally denaturing
      conditions (6 M urea), subjected to Ni(++)-Sepharose affinity chromatography,
      allowed to refold while still attached to the matrix, and eluted with 250 mM
      Imidazole. Contaminant material was partly removed by differential ammonium
      sulfate precipitation. The protein was further concentrated (Vivaspin centrifugal
      concentrator), the insoluble material (if present) was discarded, and the
      homogeneity of the dispersion was ascertained by light scattering. SDS-PAGE
      revealed that in addition to the main protein (Mr = 21 kDa), a second one of
      apparent Mr = 14 kDa was always present in variable amounts. The proportion of
      the latter tended to increase with aging of the preparation. Edman degradation
      analysis proved that the 14 kDa protein resulted from the cleavage of HAV 2A at a
      so far undetected scissile bond Gly856/Val857 of the viral polyprotein. A first
      attempt to crystallize the protein by the hanging drop procedure yielded only
      small crystals containing exclusively the 14 kDa derivative of HAV 2A. Western
      blot analysis of HeLa cell extracts that had been incubated with the His-tagged
      HAV 2A so purified failed to reveal any change in the electrophoretic mobility of
      the eukaryotic initiation factor (eIF) 4G I.

PMID- 15164620
TI  - Presence of TT virus DNA in bone marrow cells from hematologic patients.
AB  - Recent observations suggest that TT virus (TTV), in addition to liver, may also
      infect bone marrow. In this study, bone marrow samples and sera from 33 patients
      with haematological disorders and sera from 16 healthy controls were investigated
      for TTV DNA presence. Altogether TTV DNA sequences were demonstrated in bone
      marrow cells of 84.84% of patients. Moreover TTV DNA was detected in sera from
      72.72% of patients and from 93.75% of controls. N22 sequences amplified from bone
      marrow cells and serum of 3 patients were analysed, after cloning: all these
      isolates were of type 2c and 2 or 3 variants were present in each isolate. After
      single strand DNA degradation, replicative forms were detectable in BM cells.
      This finding, in addition to the detection of variants similar in the BM and in
      the serum of the same patient could suggest that BM is a site of TTV replication
      (or one of the sites) from which the virus is spread in blood.

PMID- 15164621
TI  - A comparison of RT-PCR-based assays for the detection of HAV from shellfish.
AB  - The hepatitis A virus (HAV) is the most common cause of viral infection linked to
      shellfish consumption. The lack of correlation between the fecal coliform
      indicators and the presence of enteric viruses in shellfish and their harvesting
      waters points to the need for molecular methods to detect viruses. We compared
      two RT-PCR based techniques currently available for the detection of the
      hepatitis A virus (HAV) in shellfish. Both approaches involve extraction of viral
      particles by glycine buffer and concentration of virus particles by one or two
      PEG precipitation steps. One procedure involves as RNA extraction method the use
      of oligo (dT) cellulose to select poly (A) RNA, and the other uses a system in
      which total RNA is bound on silica membrane. Comparison of the two RT-PCR based
      methods highlighted the efficiency of the first approach which is less time
      consuming and technically demanding than the second.

PMID- 15164622
TI  - Requirement of gene fadD33 for the growth of Mycobacterium tuberculosis in a
      hepatocyte cell line.
AB  - Gene fadD33 of Mycobacterium tuberculosis, one of the 36 homologues of gene fadD
      of Escherichia coli identified in the M. tuberculosis genome, predictively
      encodes an acyl-CoA synthase, an enzyme involved in fatty acids metabolism. The
      gene is underexpressed in the attenuated strain M. tuberculosis H37Ra relative to
      virulent H37Rv and plays a role in M. tuberculosis virulence in BALB/c mice by
      supporting mycobacterial replication in the liver. In the present paper, we
      investigated the role of fadD33 expression in bacterial growth within the
      hepatocyte cell line HepG2, as well as in human monocyte-derived THP-1 cells and
      peripheral blood mononuclear cells. M. tuberculosis H37Rv proved able to grow
      within HepG2 cells, while the intracellular replication of M. tuberculosis H37Ra
      was markedly impaired; complementation of strain H37Ra with gene fadD33 restored
      its replication to the levels of H37Rv. Moreover, disruption of gene fadD33 by
      allelic exchange mutagenesis reduced the intracellular growth of M. tuberculosis
      H37Rv, and complementation of the fadD33-disrupted mutant with gene fadD33
      restored bacterial replication. Conversely, fadD33 expression proved unable to
      influence M. tuberculosis growth in human phagocytes, as fadD33-disrupted M.
      tuberculosis H37Rv mutant, as well as fadD33-complemented M. tuberculosis H37Ra,
      grew within THP-1 cells and peripheral monocytes basically at the same rates as
      parent H37Rv and H37Ra strains. The results of these experiments indicate that
      gene fadD33 expression confers growth advantage to M. tuberculosis in
      immortalized hepatocytes, but not in macrophages, thus emphasizing the importance
      of fadD33 in liver-specific replication of M. tuberculosis.

PMID- 15164623
TI  - Bacterial and viral DNA in periodontal disease: a study using multiplex PCR.
AB  - Recent studies have suggested an association between periodontal disease and the
      presence of Herpesviruses, in particular: Epstein-Barr virus (EBV) and Human
      Cytomegalovirus (CMV) (Contreras et al., 1999--Contreras et al., 2000--Slots et
      al., 2000--Ting et al., 2000). In the work reported in this paper, we use a
      multiplex Polymerase Chain Reaction (PCR) to compare the presence of
      Herpesviruses and putative bacterial pathogens in patients with periodontal
      disease and in healthy individuals. Direct detection of microorganisms with PCR
      is shown to offer significant advantages in terms of time, effort and cost. The
      study detected no statistically significant differences between the prevalence of
      EBV and CMV in patients and controls. The failure to replicate previous findings
      may be due to differences in the age composition and the geographical and social
      origins of the study groups. The study detected a significant excess of HSV-1 in
      periodontal patients. This suggests that the role of Herpesviruses in the
      pathogenesis of periodontal disease deserves further investigation. The bacterial
      assay confirmed the results of previous studies showing a strong association
      between periodontitis and the presence of A. actinomycetemcomitans, P. gingivalis
      and P. intermedia.

PMID- 15164624
TI  - Serum and gastric fluid levels of cytokines and nitrates in gastric diseases
      infected with Helicobacter pylori.
AB  - This case control study presents data on the concentrations of nitrite and
      nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta
      (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8)
      and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with
      gastritis, gastric ulcer and gastric cancer are studied and grouped according to
      infection by Helicobacter pylori. The 208 patients who underwent upper
      gastrointestinal endoscopic examination were classified as follows; H. pylori
      positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori
      positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H.
      pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy
      control individuals. Gastric fluids and blood samples were taken concomitantly.
      Cytokines and nitrite and nitrate determinations were attempted as soon as
      possible after collection of the samples. Nitrite and nitrate levels of serum and
      gastric fluids of H. pylori-positive gastritis and ulcers were higher than H.
      pylori-negative gastritis and ulcers. The concentrations of total nitrite and
      nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and
      sera of H. pylori-positive gastric cancer patients were higher than H. pylori
      negative control groups. IL-1 beta level was significantly elevated in gastric
      fluid of infected cancer patients but not in serum. Taken together, the results
      suggest that an increase in cytokine-NO combination in gastric mucosa previously
      reported by many studies is not restricted to local infected gastric tissue but
      also detected in gastric fluid and sera of H. pylori-positive subjects and may
      have an important role in the pathogenesis and development of common gastric
      diseases.

PMID- 15164625
TI  - Evaluation of an IgM-ELISA test for the diagnosis of human leptospirosis.
AB  - Leptospirosis is a zoonosis with a worldwide distribution very common in most
      countries. In Italy this acute febrile illness is more frequent in the Northern
      than in the Southern regions. In the period 1994-1996, the number of cases of
      Leptospirosis in Sicily was lower with respect to the northern-central regions
      (7.2% and 73.4% respectively). Between January 1990 and December 1999, a total of
      9 leptospirosis cases were observed in the Regional Centre for Leptospirosis of
      Palermo. The patients were all males (age between 22 and 59 years) and their
      occupations varied. Laboratory diagnosis is performed by the classical
      microagglutination microscopical (MAT) but this test is very complex and time
      consuming. This study compared the classical MAT with ELISA IgM by using 19 serum
      samples from 9 patients with confirmed leptospirosis. We also tested 23 serum
      samples from blood-donors and 29 serum samples from patients with other
      infectious diseases. By the MAT and the PanBio IgM ELISA all sera from patients
      were found to be positive. Our results indicate that MAT represents the test with
      the highest degree of specificity (100%), but ELISA is simpler to perform,
      considering the favourable degree of sensitivity (100%) and specificity (95.9%).

PMID- 15164626
TI  - Development of a western blotting assay to discriminate Brucella spp. and
      Yersinia enterocolitica O:9 infections in sheep.
AB  - Outer membrane proteins (OMPs) of Rev-1 strain of Brucella melitensis were used
      in a Western blotting assay for the serological diagnosis of brucellosis in ovine
      sera. Fifty-four sheep sera were tested and divided into the following groups:
      Group A) n. 9 samples from one sheep that had been experimentally infected with
      Y. enterocolitica O:9; Group B) n. 10 samples collected from sheep infected with
      Brucella melitensis and 1 sample from a sheep vaccinated with the Rev 1 strain;
      Group C) n. 10 samples collected in "officially brucellosis-free" herds; Group D)
      n. 12 samples classified as "suspicious"; Group E) n. 12 samples classified as
      "positive". Antibodies were detected by routine tests performed for the diagnosis
      of brucellosis in serum samples of the sheep infected with Y. enterocolitica O:9
      after the 2nd week post infection. In the WB assay, sera of group B recognised a
      17 kDa protein, whereas sera of groups A, and D and 9 out of 12 of group E
      exhibited no reactivity to this protein. The results obtained encourage the use
      of the WB assay as a confirmatory test for the diagnosis of brucellosis.

PMID- 15164628
TI  - Relationship between the morphology of Candida cells and vaginal discharge.
AB  - The aim of this study was to detect whether there is a correlation between the
      dimorphic pattern of Candida cells and various types of vaginal discharge. For
      this purpose, 2861 Papanicolaoustained cervicovaginal smears were examined
      cytologically and 265 of 2861 (9.26%) were diagnosed as having Candida cells. The
      88 of 295 (29.83%) were identified as having blastospores only, 135 of 295
      (45.76%) as having "hyphae only", and 47 of 295 (15.93%) as having both
      blastospores and hyphae of candida cells. There was a significant correlation
      between the type of candida cells and vaginal discharge (p < 0.05). The white
      cheesy type vaginal discharge was the most prominent symptom for the observation
      the "hyphae only" following "blastospores only" and both blastospores and hyphae
      of Candida cells. It was suggested that hyphael form of Candida cells is the most
      pathogenic pattern and white-cheesy vaginal discharge is a marker for the
      presence of hyphael form in the vaginal mucosa.

PMID- 15164627
TI  - Evaluation of a new plate hybridization assay for the laboratory diagnosis of
      imported malaria in Italy.
AB  - A new molecular diagnostic method "Malaria-IBRIDOGEN" (Amplimedical S.p.A.-
      Bioline Division, Turin, Italy) based on a plate-hybridization assay for the
      simultaneous detection and identification of human malaria parasites was
      evaluated in this study. A target DNA sequence of the plasmodial 18S ribosomal
      RNA gene was amplified by polymerase chain reaction (PCR) and hybridized in
      microtiter wells with five biotinylated probes each specific for Plasmodium
      falciparum, P. vivax, P. malariae, P. ovale and the beta-globine human gene,
      respectively. Compared to the nested-PCR actually used in our laboratory for the
      molecular diagnosis of malaria, "Malaria-IBRIDOGEN" revealed an overall
      sensitivity of 100% (51/51) for the four human Plasmodium species testing 100
      whole blood samples from people with malaria-like symptoms and fever. Specificity
      was 92% (45/49) considering four discordant samples as "false positive" by
      "Malaria-IBRIDOGEN". The assay showed a threshold of parasite density (detection
      limit) of 0.07 P. falciparum parasites/microliter, 0.15-1.5 P. vivax
      parasites/microliter, 0.3 P. malariae parasites/microliter and 0.4 P. ovale
      parasites/microliter of whole blood, respectively. This assay could be
      successfully applied to the laboratory diagnosis of malaria as a useful aid to
      microscopy.

PMID- 15164629
TI  - Canine distemper and related diseases: report of a severe outbreak in a kennel.
AB  - An outbreak of canine distemper in a kennel of German shepherds in the province
      of Bari is reported. Six 42-day-old pups developed typical signs of canine
      distemper (fever, conjunctivitis, respiratory distress and enteritis) and died
      within 7-10 days. Neurological symptoms were observed only in one pup. Four
      additional pups, which had shown no sign of illness, were separated and
      vaccinated, but two of these developed a severe, fatal nervous form 15 days
      later. Post-mortem examination, carried out on two pups which died without
      neurological signs, showed pneumonia and enteritis, more severe in one of the two
      examined pups. Smears from the brain and the conjunctiva of both dogs tested
      positive for canine distemper virus (CDV) by an immunofluorescent assay,
      confirmed by the identification of viral RNA using RT-PCR. Bordetella
      bronchiseptica and a canine adenovirus strain, characterized as canine adenovirus
      type 2 by a differential PCR assay, were isolated from the lungs of the pup
      showing the most pronounced lesions. Furthermore, canine coronavirus was detected
      by PCR in the intestinal content of this pup, suggesting a multifactorial
      aetiology of the outbreak.

PMID- 15164630
TI  - An imported case of adult T cell leukemia in a HTLV-I-infected patient in Italy.
AB  - In this study we report the case of an acute form of ATL in a HTLV-I-infected
      Nigeria-born 27-year-old female prostitute living in Italy from February, 2001.
      The presence of HTLV-I infection was demonstrated by the detection of serum
      antibody to HTLV-I by immunoenzymatic assay and western blot analysis. In
      addition, the presence of HTLV-I proviral DNA was confirmed by a hemi-nested PCR
      in a sample of peripheral blood mononuclear cells. From an epidemiological point
      of view, it is important to report new cases of imported ATL, as it may explain
      the otherwise untraceable origin of some rare and apparently autochthonous cases
      of ATL in non-endemic areas.

PMID- 15164631
TI  - Immunity to tetanus of a rural population in a Greek county.
AB  - Tetanus is still a common problem in countries with poor health conditions. On
      the contrary, where there is a systematic program of vaccination in children it
      is very rare. The aim of this study was to check the immunity level of a
      representative sample of rural people from villages of Achaia County in Southern
      Greece. Samples were taken from 140 locals during a six-month period (January
      till July 2002). In each sample, we estimated IgG antibodies against Clostridium
      tetani toxin. A protection level of 0.1 IU/ml was set. 15.7% of the people had
      sufficient immunization cover while a statistically significant superiority of
      immunized men was found. The results of this study revealed low immunity
      percentage of the examined inhabitants and a vaccination program against the
      disease has been proposed to the local health authorities.

PMID- 15164633
TI  - Candida spp. morphotype differentiation on Sabouraud-Triphenyltetrazolium-Agar
      (STTZ-Agar) under three different experimental conditions.
AB  - One hundred and thirty-two strains of Candida spp. were cultured on STTZ-Agar at
      37 degrees C for 6 days and at 25 degrees C for 6 and 21 days to determine the
      culture conditions that would ensure maximum reproducibility in the
      discrimination of the strains of the same species. Standardization is of utmost
      importance, as varying experimental conditions can alter the results of the
      tests. Further studies are needed also implementing molecular tests to establish
      possible relationships between morphotype, genotype and virulence.

PMID- 15164632
TI  - Comparison of culture and immunoassay for detection of Escherichia coli O157 in
      raw minced meat and hamburger.
AB  - Verocytotoxin-producing Escherichia coli O157 (VTEC) is an important food-borne
      pathogen of humans. The serious complications of VTEC infection and the
      established reservoir of VTEC in cattle used for mass food production are a
      public health concern. In this study 500 samples of hamburger and minced meat
      were examined for presence of E. coli O157. For E. coli detection, Tryptic Soy
      Broth supplemented (with novobiocin and bile salts) and Sorbitol Mc Conkey agar
      were used; an automated rapid enzyme linked fluorescent immunoassay (VIDAS E.
      coli O157) was also evaluated. E. coli O157 was found in 5 samples of hamburger,
      2 strains were found to be positive for verocytotoxin production on Vero cells.

PMID- 15164635
TI  - Toxic scarlet fever complicating cellulitis: early clinical diagnosis is crucial
      to prevent a fatal outcome.
AB  - We describe a case of toxic scarlet fever in a healthy adult with streptococcal
      cellulitis of the right elbow as a result of skin abrasion. The clinical picture
      mimicked that of drug eruption after treatment of cellulitis with antibiotics.
      Among the five cases of scarlet fever complicating cellulitis, including the
      present one, reported in the English literature, four had severe systemic
      complications and two died. As a result of re-emergence of invasive streptococcal
      infections, clinicians should be aware of the differential diagnosis of scarlet
      fever in patients presenting with cellulitis and skin rash. Early clinical
      diagnosis is crucial to exclude drug eruptions, prompt initiation of antibiotic
      treatment, and prevention of the potentially fatal outcome.

PMID- 15164634
TI  - Prevalence of Chlamydophila felis by PCR among healthy pet cats in Italy.
AB  - Conjunctival swabs were taken from 60 healthy pet cats and tested for
      Chlamydophila felis by PCR assays to amplify the ompA, omp2 and groEL genes.
      Chlamydial DNA was detected in 2 (3.3%) cats, one of which had been vaccinated
      against C. felis eight months before sample collection. The nucleotide and
      predicted amino acid sequences of three genes from two cats showed 100% identity
      with the same regions amplified from conjunctival swabs of cats in the same
      geographic area.

PMID- 15164636
TI  - Trigger point injections.

PMID- 15164638
TI  - EMR success: training is the key.

PMID- 15164637
TI  - Getting an EMR up and running.

PMID- 15164639
TI  - Patient histories: how computers help.

PMID- 15164640
TI  - Protect yourself when you refer.

PMID- 15164641
TI  - How I reward excellent staffers.

PMID- 15164642
TI  - Managing anger in a managed care age.

PMID- 15164643
TI  - Code with care: you're being watched.

PMID- 15164644
TI  - What am I doing here?

PMID- 15164645
TI  - Our system lives on personal attacks.

PMID- 15164646
TI  - Is your sample cabinet a danger zone?

PMID- 15164647
TI  - I'm at least as ethical as a contractor.

PMID- 15164648
TI  - When a treatment isn't covered.

PMID- 15164649
TI  - What would you do? In this border-town dilemma.

PMID- 15164650
TI  - A shortcoming you need to know about.

PMID- 15164651
TI  - What's eating your profits?

PMID- 15164652
TI  - Helping patients use the Web wisely.

PMID- 15164653
TI  - Follow-up on the uninsured.

PMID- 15164654
TI  - Dentistry and Ayurveda--II. Basic principles.

PMID- 15164655
TI  - Oral exfoliative cytology of smokers at discrete clinical stages using AgNOR
      staining.
AB  - OBJECTIVE: This study was designed to evaluate oral exfoliative cytology of
      smokers without any clinically evident lesion and smokers with leukoplakia or
      oral cancer using AgNOR staining. STUDY DESIGN: Cytological smears of 30 smokers
      without lesion, 30 smokers with leukoplakia, 30 smokers with oral cancer and 30
      non-smokers (control group) were studied using one step silver staining method.
      The AgNOR count was established on 100 cells. Mean AgNOR count and mean % of
      cells with 5 or more AgNORs was evaluated. The count values of groups were
      compared and analysed using Student's unpaired t-test. RESULTS: The mean AgNOR
      count for control group was 2.94 +/- 0.325, smokers without lesion 3.79 +/- 0.480
      smokers with leukoplakia 3.89 +/- 0.433 and oral cancer 4.96 +/- 0.467. Mean % of
      cells with 5 or more AgNORs was 11.7, 26.5, 30.2 and 55.8 for control group,
      smokers without lesion, smokers with leukoplakia and oral cancer respectively.
      CONCLUSION: Analysis of AgNORs suggest that smoking influences proliferative
      activity in cells of smokers without any clinical lesion and that oral cancer
      shows highest proliferative activity.

PMID- 15164656
TI  - Correlation between water fluoride levels and dental caries in Davangere
      District, India.
AB  - Areas with natural fluoride in the drinking water are natural laboratories where
      the effect of fluoride on dental caries can be studied in a real life situation.
      This study was conducted to assess the prevalence of dental caries and to study
      its correlation with fluoride in the drinking water in Davangere District. 1128
      school children in the age groups of 12 and 15 years from 12 villages with
      different concentrations of fluoride in drinking water were studied. Ion
      Selective electrode method (Orion, USA) was used to estimate Fluoride
      concentrations in drinking water. Dentition Status (WHO, 1997) was used to assess
      dental caries status. Results showed that there was a significant trend towards
      reduction in dental caries with increase in water fluoride levels. A negative
      correlation between fluoride levels and mean DMFT was seen among the subjects
      with the Karl Pearson's Correlation Co efficient being -0.65 and -0.72 for the 12
      and 15 year olds respectively. It was concluded from the study that although
      dental caries was negatively associated with increasing fluoride levels, the
      problem of attendant dental fluorosis should also be considered seriously.

PMID- 15164657
TI  - LED's--future technology in curing scenario?--an in-vitro study.
AB  - The long term clinical success of composite restoration depends upon appropriate
      curing light sources. This in-vitro comparative study investigates the influence
      of conventional halogen and light emitting diode curing sources on the surface
      hardness, depth of cure and polymerization shrinkage of composites specimens of 8
      mm diameter and 10 mm in height were used to study the depth of cure. Specimens
      of dimension 8.6 mm in diameter and 2 mm in depth were used to measure the
      surface hardness and polymerization shrinkage. The results showed that in the
      long run LED's seem to have great potential to achieve a clinically consistent
      quality of composite cure.

PMID- 15164658
TI  - A comparative evaluation of medicated calcium sulphate, hydroxylapatite, mineral
      trioxide aggregate (MTA) as barrier and their effect on the sealing ability of
      furcation perforation repair material--an in vitro study.
AB  - Artificial communication between the root canal system and supporting tissues of
      the tooth lowers the prognosis of the endodontic treatment. Studies have found
      that the second most common reason for failure association with endodontic
      treatment is root perforation. Hence a study was undertaken to evaluate the
      effect of calcium sulphate, hydroxylapatite and MTA as internal matrix and their
      ability on the sealing ability of the perforation repair material (GIC) on 70
      recently extracted molar with non fused roots. MTA showed the least microleakage
      and best sealing ability and resin modified GIC when used alone without any
      internal matrix showed maximum microleakage and least sealing ability.

PMID- 15164659
TI  - Eagle's syndrome: review of literature and case report.
AB  - Eagle's Syndrome is caused by an elongated styloid process of the temporal bone
      or by ossification of the derivations of the second branchial arch. It is a
      source of craniofacial and cervical pain. Although the incidence of styloid
      process elongation is fairly common, only a small percentage of the patients
      exhibit symptoms associated with Eagle's syndrome. Like any other pain in the
      head and neck region it is an enigma. Eagle's syndrome is one of the glaring
      examples where the exact etiology eludes from the treating doctor for a long. It
      is important for the dental practitioner to be aware of this anomaly and its
      anatomic basis. Unilateral symptoms were present in one case of bilateral
      elongation.

PMID- 15164660
TI  - Gingival fibromatosis and growth hormone deficiency syndrome--report of a rare
      case and review of literature.
AB  - Oikarinen et al in 1989 reported a syndrome associated with generalized gingival
      fibromatosis and growth hormone deficiency. This is a case report of a 15-year
      old female patient who presented to the Government Dental College, Chennai with
      generalized gingival fibromatosis and growth hormone deficiency. Interestingly,
      the histopathology of the excised gingival overgrowth showed dense collagenous
      connective tissue in which were strewn calcified structures that resembled
      cementum. This syndrome is being reported for the second time after its first
      case report in 1989 by Oikarinen et al. We are herewith reporting this case for
      its rarity with a brief review of literature of syndromes associated with
      generalized gingival fibromatosis.

PMID- 15164661
TI  - Midline lethal granuloma--a clinical enigma.
AB  - Midline Lethal granuloma is characterized by progressive destruction of nose,
      paranasal sinuses and palate. Till date, the diagnosis of this mutilating process
      remains as enigma due to the non specific histological and systemic findings.
      However, over the years the clinicians have been able to divide the "Lethal
      midline granuoloma syndrome" into clinical entities: Idiopathic midline
      destructive disease, Wegener's granulomatosis, polymorphic retiaculosis and Non
      Hodgkins lymphoma. This article attempts to distinguish between these disease
      entities in the light of 2 case reports of Idiopathic midline destructive
      disease.

PMID- 15164662
TI  - Basaloid squamous cell carcinoma report of a case and review of literature.
AB  - Basaloid squamous cell carcinoma (BSCC) is an aggressive distinct variant of
      squamous cell carcinoma that mandates recognition as a separate entity owing to
      the difference in its clinical behaviour. Histologically this tumor can mimic
      other neoplasms like adenoid cystic carcinoma, neuroendocrine carcinoma and basal
      cell adenocarcinoma. BSCC occurs most commonly in older men and has a site
      predilection for the upper aero-digestive tract. We report a case of basaloid
      squamous cell carcinoma for its relative rarity, which was diagnosed in a 52 year
      old woman, with a brief review of literature.

PMID- 15164663
TI  - The fruits of new knowledge.

PMID- 15164664
TI  - Usability basics for clinical nurse specialists.

PMID- 15164665
TI  - Nosocomial infections. An issue of patient safety, Part 2.

PMID- 15164666
TI  - Selective serotonin reuptake inhibitors and abnormal bleeding. Implications for
      the clinical nurse specialist.

PMID- 15164667
TI  - Nurse entrepreneurship. Taking an invention from birth to the marketplace.

PMID- 15164668
TI  - The effectiveness of a CNS-led community-based COPD screening and intervention
      program.
AB  - PURPOSE/OBJECTIVES: The purpose of this study was to evaluate the effectiveness
      of a screening program in identifying undiagnosed individuals with chronic
      obstructive pulmonary disease (COPD). THEORETICAL RATIONALE: Underdiagnosis of
      COPD is common. Symptoms do not usually become apparent until the disease is
      advanced. Consequently, by the time a diagnosis of COPD is made, based on
      symptoms, the individual has often lost up to 50% or more of their original lung
      capacity. Early diagnosis and intervention has been demonstrated to have an
      impact in slowing the progression of the disease. The study was based on the
      premise that when individuals become self-aware of their risk factors related to
      disease, they are more likely to change their behaviors. The Transtheoretical
      Model describes how individuals move through various stages of change and how
      they can be helped in transitioning from one stage to another. DESCRIPTION OF THE
      PROJECT: Subjects (n = 243) were recruited via letter, newspaper, and physician
      referral. The screening program consisted of (1) pulmonary function testing using
      a handheld spirometry device, (2) education about the test results and COPD, and
      (3) smoking cessation counseling. Current smokers and those found to have
      obstruction were contacted at 8 to 12 weeks after screening. OUTCOME: Results
      indicated that 209 (86%) of participants were at risk for developing COPD as
      evidenced by current or past smoking status. Mild to moderate stage obstructive
      disease was found in 55 subjects (23%). Of 61 subjects contacted after the
      screening, 29 smokers (47%) indicated they had stopped smoking, were in the
      process of quitting, or were seriously considering quitting. CONCLUSIONS: Results
      support the use of a community-screening program to identify and help modify risk
      factors for COPD. IMPLICATIONS FOR NURSING PRACTICES: This project provides an
      example of how a clinical nurse specialist (CNS) can exercise all the spheres of
      CNS influence: the patient/client sphere, the nursing personnel sphere, and the
      organization sphere. In addition, the COPD screening project demonstrated how a
      CNS can successfully lead and direct a community initiative and influence others
      in changing behavior to enhance their state of health.

PMID- 15164669
TI  - Nursing considerations in psychotropic medication-induced weight gain.
AB  - PURPOSE/OBJECTIVES: The purpose of this clinical project is to emphasize the
      importance of prevention/treatment of psychotropic medication-induced weight
      gain. Professionals who work with patients taking psychotropic medications should
      provide a weight management program specifically designed to address the unique
      needs of the mentally ill patient. BACKGROUND/RATIONALE: Psychotropic medications
      used in the treatment of serious psychiatric disorders are associated with body
      weight gain. Medication-induced weight gain can lead to serious health issues and
      noncompliance with needed treatment. DESCRIPTION OF THE PROJECT: Current
      literature and discussion of possible mechanisms of pharmacologically induced
      weight gain are reviewed. Health issues related to weight gain are summarized.
      The nursing process is then used to assess, diagnose, plan, implement, and
      evaluate a program of weight management for pharmacologically treated psychiatric
      patients. OUTCOMES: Research findings demonstrate an increased rate of obesity in
      pharmacologically treated psychiatric patients. This phenomenon is probably
      multifactorial and leads to physical complications, psychological consequences,
      and noncompliance with treatment. Patients with mental health disorders can
      effectively control their weight if they are supported by a weight management
      program specifically designed to meet their needs. INTERPRETATION/CONCLUSIONS:
      Early intervention can prevent or minimize weight gain. Weight gain when it does
      occur can be reversed through a program of weight management. Nurses can utilize
      the nursing process to develop a weight management program that provides for the
      special needs of mentally ill clients. IMPLICATIONS FOR NURSING PRACTICE:
      Psychotropic medication-induced weight gain is an often neglected problem that is
      not readily addressed in the clinical setting. On the basis of the scope of the
      problem, nurses should view medication-induced weight gain as a priority. Nurses
      are in a unique position to design and implement an individualized weight
      management program through the collaborative and holistic strategies that the
      nursing process provides.

PMID- 15164671
TI  - Clinical nurse specialist profile.

PMID- 15164670
TI  - Research ethics, informed consent, and participant recruitment.
AB  - PURPOSE/OBJECTIVES: This analysis explores ethical issues and challenges in
      participant recruitment. BACKGROUND/RATIONALE: The clinical nurse specialist
      (CNS) as researcher faces many issues and challenges, including ethical issues of
      informed consent. Balancing participant expectations of care with the research
      purpose is often challenging. DESCRIPTION OF THE ANALYSIS: This analysis
      synthesizes literature in key areas related to participant recruitment. Medline,
      CINAHL, and hand search techniques were used to collect relevant materials for
      this analysis. OUTCOMES: Key issues related to ethics and informed consent
      included readability of consent documents, education level, relationships between
      participants and health care providers, therapeutic misconception, and illness
      severity. Related issues include compensation of participants, recruitment of
      special populations, and the role of clinical research associate.
      INTERPRETATION/CONCLUSIONS: The CNS faces considerable ethical and logistical
      challenges in any research study. Strategies to support the CNS as researcher are
      available. IMPLICATIONS FOR NURSING PRACTICE: Increased awareness of ethical
      issues and challenges in recruitment is important for the CNS to creatively
      design strategies to enhance recruitment and retention in research studies.

PMID- 15164672
TI  - Effectiveness of antimicrobial adjuncts to scaling and root-planing therapy for
      periodontitis.

PMID- 15164673
TI  - [Risk factors and risk indicators of destructive periodontitis. II. Genetic risk
      factors (literature review)].
AB  - After the latest advances in genetic research and basic genetic terminology
      having been briefly discussed in the second part of the paper, the chromosomal,
      monogenic as well as polygenic inherited disorders affecting normal PMN leukocyte
      functions are overviewed. From Down's syndrome to the Papillon-LeFevre syndrome,
      the different leukocyte adherence deficiencies and also certain inherited
      metabolic bone diseases, like hypophosphatasia are discussed. Than the recent
      advances in the research of the role of genetic polymorphisms of lymphokines and
      certain white blood cell's Fc receptor polymorphism in the development and
      progression of periodontitis are discussed in details. Finally the role of the
      ethnic modifying factors in the aetiology of destructive periodontal disease are
      discussed.

PMID- 15164674
TI  - [Literature survey of apexification in connection with three cases].
AB  - Endodontic treatment of three non-vital immature teeth is discussed. According
      Moorrees et al. root formation was in the stage two, six and four respectively.
      After access to the root canal, removing necrotic pulp and effective chemo
      mechanical cleansing, Ca(OH)2 paste was used as a temporary filling material in
      each case. In two cases after closing the apical opening, permanent obturation
      was performed with half heated gutta-percha and lateral condensation to obtain a
      good seal. In one case permanent filling of the canal occurred with gutta-percha
      and AH26 as a sealer. In the first case two years, in the second case five years
      after obturation of the root canal with gutta-percha, periapical healing was
      evident in the control radiograph. In the third case using gutta-percha with AH26
      as a sealer after two years new periapical lesion has developed. On the bases of
      literature data and our experiences in the case of non-vital immature teeth.
      Ca(OH)2 paste is the best temporary filling material to induce apexification
      process, and the half heated gutta-percha obturation is the most suitable
      permanent root filling material.

PMID- 15164675
TI  - [Possibilities of dowel core fabrication under the anchors of fixed restorations-
      case report].
AB  - Frequent consequence of inadequate constructions post & core placement in root
      canal treated abutment teeth is loosening of the anchors. Patients frequently
      seeks dental treatment too late, only when the whole abutment gets decayed and
      totally vanished. Providing the dentist is able to remove the fixed restoration
      without damaging the anchors the same restoration can be replaced if the dentist
      can create a new dowel core under the retainer. That is a big question if the
      fabrication of such a properly fitting dowel core is possible tha provides a
      durable fixation without the remaking the whole bridgework? Dowel cores can be
      fabricated using the direct and indirect techniques. The advantage of the direct
      method is that it needs only one appointment, while the indirect technique
      provides all the advantages of the laboratory accuracy. The technique of
      fabrication will be shown on two patient's cases.

PMID- 15164676
TI  - [Measurement of periapical pressure created by occlusal loading].
AB  - The aim of this study was to develop an in vitro model in which the pressure in
      the periapical tissues can be measured during loading. Extracted human maxillary
      central incisors were embedded into resin blocks that had physical
      characteristics similar to bone and periodontal ligament. Each tooth was loaded
      with 20, 40, 50, 60, 75, 85, 100, 200, 300 and 450 N vertical forces from the
      incisal edge of the crown; this procedure was carried out three consecutive
      times. A minute resistor embedded in the periapical space was used to detect
      apical pressure changes during occlusal loading. The ratio of apical pressure
      changes (delta P) to the loading force changes (delta F) was calculated. The
      periapical pressure detected was in direct proportion to the loading force. The
      mean value of delta P/delta F was 5.994 kPa/N (SD = 2.04). Direct proportionality
      was found between the coronal loading and the apical hydrostatic pressure. The
      (delta P)/(delta F) ratio determined in this study makes it easier to estimate
      the apical hydrostatic pressure values during occlusal loading of single rooted
      teeth. In this study the apical pressure generated under occlusal loading was of
      the same magnitude as that estimated with the finite element method.

PMID- 15164677
TI  - [Some background data about the high dental anxiety of the Hungarian population].
AB  - 100 dental patients waiting for hypnotic dental treatment (n = 100, 58 female, 42
      male, mean age: 36.4 +/- 10.6 yr.) was investigated about their perceived origins
      of dental anxiety. Dental anxiety levels (DAS, DFS) and general anxiety were
      measured as well. Mean dental anxiety scores were high (DAS: 12.5 +/- 3.3; DFS:
      47.9 +/- 17.3). The most frequent reason of high dental anxiety was previous
      painful dental treatment (20.0%), dislike of dentist's behaviour (15.0%),
      treatment error (5.0%), and "other reasons" (4.0%). A large amount of the
      patients (48.0%) did not know what to expect, and 8.0% indicate no fear related
      to dentistry. Previous painful dental treatment induced the highest dental
      anxiety (DAS: 15.1 +/- 3.1; DFS: 58.1 +/- 20.3), followed by the "other reasons"
      (DAS: 14.0 +/- 0.8; DFS: 50.5 +/- 13.5), treatment error (DAS: 13.0 +/- 3.7; DFS:
      49.0 +/- 16.1), and dislike of dentist's behaviour (DAS: 11.4 +/- 2.8; DFS: 45.0
      +/- 12.5). Increased general anxiety was found in the groups indicated previous
      painful dental treatment, "other reasons", and no expectation.

PMID- 15164678
TI  - Strategies for improving minority healthcare quality.

PMID- 15164679
TI  - International nurses share the benefits of membership in ONS.

PMID- 15164680
TI  - The medical waste revolution is on the horizon: Part II.

PMID- 15164681
TI  - Dracunculiasis eradication.

PMID- 15164682
TI  - Investment in water and sanitation yields health and economic benefits.

PMID- 15164683
TI  - The QT interval enters mainstream medicine.

PMID- 15164684
TI  - Patient co-payment for prescription medicines across Europe--how do we compare?

PMID- 15164685
TI  - Schizophrenia susceptibility genes: recent discoveries and new challenges.

PMID- 15164686
TI  - Audit of thromboprophylaxis in women undergoing caesarean section.
AB  - Thromboembolism is a major cause of maternal mortality. Pregnancy is associated
      with an increased risk of thromboembolic diseases, with an even greater risk in
      women undergoing caesarean section. Since the introduction of the RCOG guidelines
      in 1995 on thromboprophylaxis for women undergoing caesarean section, there has
      been a significant reduction in the number of women dying from pulmonary embolism
      in the UK. The aims of our study was to conduct an audit cycle to assess our
      compliance with RCOG guidelines for thromboprophylaxis in women undergoing
      caesarean section to introduce changes in practice based on the observations of
      this audit, and to re-audit our practice to assess the effect of the changes. A
      retrospective audit of 100 women undergoing caesarean section was done in the
      Rotunda Hospital in June 2001. Changes in practice were introduced based on the
      findings of this audit. Obstetricians were asked to complete a checklist pre
      operatively and to assign the patients a risk category-low, moderate or high.
      Prophylaxis was prescribed based on this risk assessment. Following the
      introduction of this change in practice, we re-audited 100 women delivered by
      caesarean section in June 2002. In the first audit, risk assessment was as
      follows: 20 low, 75 moderate and 5 high. Twenty-one of 75 (28%) of moderate risk
      patients in the first audit received appropriate prophylaxis. In the re-audit,
      risk assessment was as follows: 33 low, 66 moderate and 1 high. Following the
      introduction of new clinical practice, 45 of 66 (68%) of those in the moderate
      risk group received appropriate prophylaxis. All women in the low risk groups
      received appropriate prophylaxis in both audits. Our audit cycle of
      thromboprophylaxis in women undergoing caesarean section has demonstrated that
      the introduction of new clinical practice resulted in greater compliance with the
      RCOG guidelines, but further improvement could be achieved. These observations
      are discussed and recommendations are made to further improve compliance with
      RCOG guidelines.

PMID- 15164687
TI  - Endoscopic stapling vs conventional methods of surgery for pharyngeal pouches:
      results, benefits and modifications.
AB  - Endoscopic stapling of pharyngeal pouches using the Endo GIA-30 stapling gun is a
      relatively new technique. We compared the outcome of patients who had endoscopic
      stapling of their pharyngeal pouch with those who had excision of the pouch along
      with a cricopharyngeal myotomy using conventional methods. A total of 19 patients
      were included in the study, 9 in the conventional technique group and 10 in the
      endoscopic stapling group. Data was collected by reviewing patient records and a
      postal questionnaire. Median stay in hospital for the conventional technique
      group was 10 days while in comparison the average stay in hospital for the
      endoscopic stapling group was 3.9 days. The median fasting time for the
      conventional technique group was 6 days while all patients in the endoscopic
      stapling group commenced oral feeding on day one post surgery. The postal
      questionnaire showed that endoscopic stapling was associated with a high patient
      satisfaction rate. We conclude that endoscopic stapling of pharyngeal pouches has
      similar results to the conventional open technique, but is less invasive and
      associated with a shorter stay in hospital. We also discuss a technical
      modification employed in the stapling of small pouches with thick anterior walls.

PMID- 15164688
TI  - Brain death and organ donation: an audit in the Irish National Transplantation
      and Neurosurgical Centre.
AB  - We set out to identify the reasons why potential organ donors (PODs) fail to
      become actual donors and the causes of under-utilization of organs offered for
      donation. We audited 354 patients who died in the intensive Care Unit over 18
      months. Of 155 PODs, 78 (50%) did not undergo brain stem testing (BST) because of
      (i) unavoidable death from non-CNS causes before BST (n = 50), (ii) treatment
      withdrawal without BST (n = 17) and (iii) preconditions for BST were not
      fulfilled (n = 11). Brain death was confirmed in 75 patients. Relatives refused
      consent for donation in 25 patients organ donation was not discussed with the
      family in 6, and medical contraindications to organ donation prevented donation
      in 5. Thirty seven (24% of all PODs) became organ donors who provided a total of
      216 organ. All donated kidneys were utilized but unsuitability and logistic
      issues prevented utilization of 20% and 13% of all donated organs respectively.
      The commonest reason for failure to utilise potential organ donors was failure to
      perform BST. In most cases this was because BSTs were not possible but more
      aggressive management of and the routine performance of BST in all PODs could
      increase the number of donors. Not approaching relatives to ask consent for organ
      donation and a high rate of refusal by relatives also led to loss of organ
      donors.

PMID- 15164689
TI  - Injuries sustained by recruits during basic training in Irish Army.
AB  - The incidence of recruit injuries during basic training in the Irish Army is, to
      date undocumented. In this retrospective cohort study, the medical records of 415
      recruits are examined. The lower limb predominated as the anatomical site of the
      majority of injuries. The overall incidence of male 'first time' injuries was
      56.96 per 1000 man-week training. The corresponding female figure was 99.26.
      Female recruits lost an average of 8.2 days per injury, while the male figure was
      5.69 days. The injured female recruit was also more likely to sustain a further
      injury than her male colleague. Risk factors and possible prevention strategies
      are discussed.

PMID- 15164690
TI  - Implications of the increasing female participation in the general practice
      workforce in Ireland.
AB  - Almost one in three Irish general practitioners (GPs) are now women, a ratio that
      has doubled since the early 1990s. The increase in numbers of women entering
      general practice training looks likely to continue and will have a formative
      influence on the future of general practice. This study investigates the
      implications for Irish general practice of the increasing feminization of the
      workforce. Questionnaires were sent to all (200) Irish vocationally trained
      female General Practitioners qualifying between 1995 and 2001. Sixty eight
      percent of respondents were currently working in full-ltime general practice. A
      majority wish to remain in general practice (88%) and potentially up to 90%
      intend to work part-time in the future. The ideal future work practices of this
      cohort are part-time partnerships, and over 50% are not in a position to work out
      of hours. To facilitate the career and working intentions of female vocationally
      trained GPs and to retain their services, there needs to be increased flexibility
      of hours of work, increased part-time partnerships and an Irish retainer scheme
      that will accommodate female GPs who cannot work full-time because of family
      commitments.

PMID- 15164691
TI  - Demographic profile of the elderly population in Dublin accident and emergency
      hospital catchment areas.
AB  - The Dublin metropolitan area is now divided into a number of clearly defined
      accident and emergency (A & E) catchment areas since the closing of the smaller
      inner city hospitals and the opening of newer hospitals on the periphery of the
      city. We examined the demographic profile of the elderly population in Dublin
      city and county served by each of the new catchment areas. Whilst the elderly
      population make up 9.9% (105,188) of the Dublin population (1996 census) they
      make up over 20% of the A & E attendances and up to over 40% of the A & E
      admissions in major Dublin hospitals. There is a wide variation in the percentage
      elderly population in each hospital catchment area with inner more settled city
      areas having a much higher percentage elderly population over those hospital
      catchment areas that serve newer housing areas. We also looked at the level of
      deprivation. Combining the two most deprived levels St James's Hospital had the
      largest absolute number and the highest percentage of deprived elderly 12,736
      (51.1%) followed by the Mater 6,919 (32.9%), Beaumont 5371 (31.5%), James
      Connolly 2,983 (38.1%), Tallaght 2012 (22.3%) and St Vincent's Hospital 1987
      (7.7%). Hospitals with high numbers of elderly and serving deprived catchment
      areas face particular resource problems in meeting the needs of the population
      that they serve. A significant increase in the provision of publicly funded
      community facilities and long stay accommodation is required to meet the needs of
      the large number of deprived elderly in the inner city area. Failure to respond
      to these demographic challenges will have a profound effect on the ability of
      hospital emergency services to meet the increasing pressures posed by the high
      volume of acutely sick economically deprived elderly presenting to hospital
      accident and emergency departments.

PMID- 15164692
TI  - Dental and maxillofacial abnormalities following treatment of malignant tumours
      in children.
AB  - There is a wide range of malignant tumours with an embryonic origin that can
      affect children in their early childhood including Rhabdomyosarcoma,
      Osteosarcoma, Chloroma, Retinoblastoma and neuroblastoma. Different protocols
      have been developed over the past years to treat these tumours and different
      combinations of radiotherapy, surgery and chemotherapy were used. This improved
      the survival rate considerably. This treatment has a marked effect on growth of
      soft and hard tissues in the affected regions of the head and face, leading to
      facial and dental abnormalities that become evident with growth. The great effect
      of radiotherapy and chemotherapy on craniofacial skeletal growth should be
      considered in all cases undergoing treatment for tumours. The resulting dental
      and maxillofacial abnormalities should be expected in all cases and its
      management require involvement of different members of the medical team including
      maxillofacial surgeon, restorative dentist, orthodontist, psychologist,
      dietician, speech therapist, the patient and the parents in order to achieve
      maximum results. This paper presents four patients who underwent radiotherapy and
      chemotherapy for treatment of embryonic tumours and discusses the main side
      effects of the treatment.

PMID- 15164693
TI  - Running with the squirrels.

PMID- 15164694
TI  - Making the transition: document delivery at the crossroads of paper and
      electronic delivery.

PMID- 15164695
TI  - Christine Chastain-Warheit--winner of the 2004 Lois Ann Colaianni Award for
      excellence and achievement in hospital librarianship.

PMID- 15164696
TI  - Acting the part. While Cover the Uninsured Week adds star power to its campaign,
      few viable solutions are in the works.
AB  - While Cover the Uninsured Week may have a celebrity spokesman in TV star Noah
      Wyle, the campaign is still lacking viable legislative solutions. As Sen. Jay
      Rockefeller, left, noted at a news conference kicking off the event, the "me
      first" special interests of the various healthcare trade associations have made
      putting together a comprehensive approach to the uninsured problem nearly
      impossible.

PMID- 15164697
TI  - A new dawn. Board picks veteran HCA exec to lead HealthSouth.

PMID- 15164698
TI  - Mass exodus. Catholic system CEO 4th to step down in 2 months.

PMID- 15164699
TI  - Relocation, relocation. Tenet plans to move headquarters to Dallas.

PMID- 15164700
TI  - Piedmont on prowl. Atlanta system eyes new partner after separation.

PMID- 15164701
TI  - Looking for a solution. Review process questioned after Maryland fiasco.

PMID- 15164702
TI  - The perils of serving two masters. Healthcare execs are slow to recognize why you
      can't sit on both sides of the table.

PMID- 15164703
TI  - Unequal access. Smaller hospitals still at a disadvantage in terms of capital
      access. But often it's where you are, not how big you are, that really matters.

PMID- 15164704
TI  - Deep trouble. A few preventive steps can head off deadly complications of deep
      vein thrombosis. But many hospitals fail to address the risk.

PMID- 15164705
TI  - [Correlation between otoacoustic emissions and BAEP. The importance of their
      combined use].
AB  - Auditory Brainstem Response (ABR) of 50 newborn with negative transient evoked
      acoustic emissions (OEAT) was performed. 54% of them had no family history of
      sensorineural hearing loss (SHNL) and no risk factors were found. In 70% of cases
      ABR recording was negative. Follow up did show that 60% of them had normal
      recordings of hearing and in a 40% different stages of hearing loss were seen. To
      establish a definitive diagnosis a 1 to 9 month period is necessary.

PMID- 15164706
TI  - [Evaluation of electroneurography as a prognostic method in the development of
      peripheral facial paralysis].
AB  - Electroneurography (EnoG) is a prognostic test used in the assessment of the
      peripheral facial nerve paralysis. We believe that when performed in standard
      conditions and together with the clinical evolutive parameters, it is very useful
      to reveal the critical time for a more radical treatment. We studied 44 patients;
      13 patients had greater than 90% neural degeneration on EnoG. 5 of them underwent
      facial nerve surgical decompression due to a poor clinical outcome and up to
      three of these patients had a normal facial function after this.

PMID- 15164708
TI  - [Somnoplasty: treatment of chronic snoring using radiofrequency irradiation of
      the palate].
AB  - The goal of this study is to evaluate the efficacy and the safety of tissue
      reduction of the palate by means of radiofrequency for the treatment of snoring.
      Fifty-three patients were evaluated. Eight of them (15%) met criteria for mild
      OSAS. All of them underwent RF energy treatment with several ablation sites and
      the mean total energy administered was about 2500 J per treatment session. 40
      patients (75%) underwent an additional RF treatment and the energy administered
      in the second session was the same as in the first one. We evaluated
      postoperative pain, snoring and the satisfaction of the patient and his
      enviroment. After a mean follow-up of 20 months no adverse effect was reported.
      The success diminishes with time as happens other surgical procedures (UPPP or
      LAUP) but the absence of serious adverse side-effects and the minimal
      postoperative pain support the use of RF as an effective procedure for reducing
      snoring.

PMID- 15164707
TI  - [The Connecticut Chemosensorial Clinical Research Center olfaction test: values
      in healthy volunteers].
AB  - OBJECTIVE: To know the values of the olfactory test (CCCRC) performed in healthy
      people. To analyse how the age and sex affect the test. MATERIAL AND METHODS:
      Descriptive study in 100 volunteers with no olfactory disorders. We used CCCRC
      olfactory test, which it has an odor threshold component, an odor identification
      component and a composite score. We analysed how age and sex variables affect
      olfactory test data, listing a t-Student test. The size sample is calculated to
      0.05 alfa error. RESULTS: Threshold test data mean was 5.8. Identification test
      data mean was 7.5. Composite score mean was 6.7. CONCLUSION: Age is a significant
      factor in our study but not sex. Sample size is sufficient to analyze normal
      values. Our results are similar to other authors.

PMID- 15164709
TI  - [Induction chemotherapy using vinorelbine, cisplatin, and UFT in advanced
      pharyngeo-laryngeal carcinomas: results of a phase II study].
AB  - OBJECTIVE: To evaluate the results of an induction chemotherapy protocol with
      Vinorelbine, UFT and Cisplatin (UFTVP). METHODS: 93 patients with laryngo
      pharyngeal squamous cell carcinoma in stage III or IV were prospectively entered
      into a protocol to receive four cycles of UFTVP. Responders followed definitive
      radiation therapy. Nonresponders underwent conventional surgery with
      postoperative radiation. RESULTS: Following chemotherapy nodal response (complete
      in 28% and partial in 33%) was less than that the primary site (complete in 60%
      and partial in 30%), p = 0.002. With a median follow-up of 62 months, the Kaplan
      Meier 5-year survival was 45%. Successful larynx preservation was achieved in 50%
      of patients with laryngeal cancer and in 29% of patients with hypopharyngeal
      cancer. Lymph node metastases and pharyngeal localization were found to be
      significant negative factors with regards to survival. CONCLUSIONS: UFTVP is an
      active regime of chemotherapy in advanced squamous cell carcinoma of the pharynx
      and larynx. Results differ according to the localization, having significantly
      better rates of survival and organ preservation in the laryngeal cancers that in
      those of the pharynx.

PMID- 15164710
TI  - [Quality of life in patients treated for head and neck cancer].
AB  - In this paper we have studied the quality of life of patients that underwent
      treatment for an early laryngeal carcinoma in comparison to others with an
      advanced head and neck cancer. We have studied 62 patients (T1N0M0, T2N0M0) with
      laryngeal carcinoma diagnosed between 1990 and 1998. We have applied the European
      EORTC QOL C-30 questionnaire, and more specifically its head and neck module (H&N
      35). The results were compared with a heterogeneous group of 48 patients with
      different degrees of head and neck cancers. The quality of life of our patients
      who were treated for an early glottic cancer was better in many functional scales
      of the EORTC and in many specific symptom scales of the H&N 35, but not in global
      cancer symptoms.

PMID- 15164711
TI  - [Isolated lymphatic recurrences in patients with head and neck carcinomas].
AB  - OBJECTIVE: Recurrencies of lymphatic metastasis implies a poor prognosis in
      patients with head and neck carcinoma. The aim of our study is to analyse the
      results of salvage treatment after an isolated regional tumour recurrence.
      MATERIAL AND METHODS: Retrospective study of 144 patients with head and neck
      carcinoma with an isolated neck recurrence. The treatments used, regional control
      and patient's survival were analysed. RESULTS: Sixty-four percent (92/144) of
      patients were not candidates to salvage treatment with radical intention. Salvage
      surgery was performed in 36% (52/144) of patients, with a survival of 46% in this
      group of patients. Previous treatment of the neck was the most relevant variable
      to decide a salvage surgery. Patients treated initially with neck dissection had
      the worst prognosis. CONCLUSIONS: The existence of a regional recurrence has a
      bad prognosis, with 16% 5-year survival. Only 36% of patients were considered
      candidates to salvage treatment, achieving 46% of survival.

PMID- 15164712
TI  - [Asymptomatic bilateral pharyngocele].
AB  - The diverticula of the lateral wall of the pharynx are called pharyngoceles. We
      present a case of a 71-year old male in whom we discovered, by chance, a
      bilateral pharyngocele. Given their scarcity, we review the characteristics of
      the process, highlighting the relevance of the oesophagopharingeal barium
      swallow. Finally, we describe two possible anatomical locations of the herniated
      sac.

PMID- 15164713
TI  - [Recurrent polychondritis: apropos of a case].
AB  - We present a case of relapsing polychondritis which presented as hypoacusis and
      showed several peculiarities. The initial diagnosis was serous otitis. After a
      more careful study we found certain details which made us suspect a relapsing
      polychondritis. The diagnosis was confirmed by a biopsy of the nasal cartilage
      and a detailed systemic study was performed. As distinctive characteristics we
      found a mixed hypoacusis, in which the sensorineural component was partially
      recovered following corticoid treatment.

PMID- 15164714
TI  - [Bacteria of Bartonella genus: characteristics, pathogenicity factors and methods
      of molecular-genetic investigation].
AB  - Bartonella bacteria are an agent of a variety of human and animal diseases whose
      etiology used to be unknown. The survey contains a description of the above
      bacteria with the established pathogenicity factors and with the molecular and
      genetic approaches to studies of genes' functions and of their regulation being
      in the focus of attention. Modern methods related with the genus-specific and
      species-specific determination and identification of Bartonella bacteria are
      discussed.

PMID- 15164715
TI  - [A comparative analysis of genomes of virulent and avirulent strains of Vibrio
      cholerae O139].
AB  - A comparative analysis of the genome of V. cholerae O139 strains isolated in
      Russia's territory from patients with cholera and from the environment showed
      essential differences in their structures. The genome of clinical strains
      possessed all tested genes associated with virulence (ctxAB, zot, ace, rstC,
      rtxA, hap, toxR and toxT) and the at-tRS site for the CTXp phage DNA integration.
      As for the O139 V. cholerae chromosome strains isolated from water, 70% of the
      studied genes (ctxAB, zot, ace, rstC, tcpA, and toxT) and the attRS sequence were
      not detected in them. A lack of the key virulence genes in O139-serogroup "water"
      vibrios, including genes of toxin-coregulated adhesion pili. (that are receptors
      for the CTXp phage), and of the attachment site of the above phage are indicative
      of that the O139 V. cholerae strains isolated from open water sources located in
      different Russia's regions are epidemically negligible.

PMID- 15164716
TI  - [Identification of the open reading frame coding transposase of Bordetella
      pertussis RS-element].
AB  - A computer-aided analysis of the repeating sequence of Bordetella pertussis
      chromosome (RSBP3) revealed 3 open reading frames, one of whose (ORF1) can code a
      protein whose structure and properties are similar to those of transposasas, i.e.
      enzymes in charges for the traveling of migrating genetic elements of pro- and
      eukaryote. Mutants of the RSBP3 insertion sequence with the affected and
      unaffected ORF1 sequence were constructed in order to substantiate the above
      assumption. Two independent experimental models (formation of inter-plasmid co
      integrates and of co-integrates between plasmid and E. coli chromosome) were used
      to show that the RSBP3-stimulated formation of co-integrates is only true for
      plasmids containing RSBP3 with the unaffected ORF1 sequence. An activity of the
      Hpr protein (a component of the phosphoenolpyruvate-dependent phosphotransferase)
      was proven to influence the formation process of inter-plasmid co-integrates.

PMID- 15164717
TI  - [Genotyping of the Francisella tularensis strains isolated from natural foci of
      tularemia in the Rostov region by multilocus VNTR analysis].
AB  - On the basis of an analysis of the VNTR alleles' distribution in 109 strains of
      F. tularensis it was established that 19 genotypes of the disease causative agent
      circulated in the Rostov Region from 1945 to 2002. The microbe-provoked infection
      episodes can be divided into polyclonal, monoclonal and cluster ones. A
      retrospective analysis of the genotypes' distribution is indicative of that
      strains of similar or of closely-related genotypes circulate simultaneously in
      the studied territory. All investigated F. tularensis strains could be
      differentiated into two groups; strains, whose genotypes are encountered almost
      evenly within the entire Region's territory, belong to group 1; and strains of
      group 2 displayed a trend towards being geographically bound. Isolations of
      cultures with similar (close) genotypic features made in prolonged time periods
      suggest that a part of F. tularensis clones can persist for a long time in
      environmental foci. A set of strains described by genotype can provide a
      foundation for a database of the tularemic microbe culture within the geo
      information system of the South Federative Okrug of Russia.

PMID- 15164718
TI  - [Expression regulation of the protelomerase gene of the bacteriophage N15].
AB  - The N15 bacteriophage, when in the lysogenic state, does not integrate into the
      chromosome; in fact, it exists as a linear plasmid with the covalently closed
      ends. Upon infection, the phage DNA circularizes via its cohesive ends, after
      which a specific enzyme, the N15 protelomerase, cuts the circular molecule thus
      generating a linear plasmid with the covalently closed telomeres. Protelomerase
      generates, as the replication of plasmid prophage proceeds, the hairpin telomeres
      in replicated molecules. We identified the promoter of the protelomerase gene and
      demonstrated that it could be repressed presumably due to its binding with 3 tosL
      sites overlapping the promoter. We also found the transformation efficiency of E.
      coli cells of linear DNA with hairpin telomeres to be approximately 100-fold
      lower versus the circular DNA of the same size. At the same time, presence of the
      N15 prophage or of the protelomerase-expressing vector enhances, in a strain
      being transformed, the efficiency of its transformation by linear DNA up to a
      level ensured in transformation by circular plasmids. We believe that
      protelomerase, while binding with the hairpin telomeres, protects the latter from
      degradation by cellular nucleases.

PMID- 15164719
TI  - [Molecular typing of the tick-borne encephalitis virus isolated from patients
      with different-infection severities in the south of Russia's Far East].
AB  - The thick-borne encephalitis virus (TBEV), which is widespread in the Eurasian
      continent, belongs to the Flaviviridae family, Flavirus genus, and comprises the
      Far Eastern, Siberian and West European subtypes. It was for the first time that
      the gene part of the E 24 strain envelope glycoprotein of TBEV, which caused
      infection in residents of the South of Russia's Far East, was analyzed. It was
      established that the TBEV Far-Eastern subtype causes different-severity disease
      cases ranging from the focal ones with the lethal outcome to latent infection
      forms. On the basis of the phylogenetic analysis, the Far-Eastern subtype was
      shared between 4 sub-clusters, 2 of which constitute a majority of the analyzed
      TBEV strains.

PMID- 15164721
TI  - Editor in the eye of a storm.

PMID- 15164720
TI  - [Genetic variability of the nucleocapsid protein of the virus of the porcine
      reproductive and respiratory syndrome].
AB  - The porcine reproductive and respiratory syndrome (PRRS) is a contagious viral
      pathology caused by PRRS virus. There are 2 types of the above virus--the
      European and American ones. Distribution patterns of the PRRS virus were studied
      for Russia and Byelorussia. Above 700 porcine sera obtained from 32 households of
      21 Russia's administrative regions and from 19 households of 6 Byelorussia's
      administrative regions were tested for presence of antibodies to the PRRS virus.
      Simultaneously, the samples were tested for virus presence by polymerase chain
      reaction (PCR). It was proven serologically that the PRRS virus is widespread in
      the territories of Russia and Byelorussia. Noteworthily, all field isolates found
      in Russia and Byelorussia belong to the European type. Not a single viral isolate
      of the American PRRS type was found. The nucleocapsid (N) recombinant protein was
      obtained on the basis of the Russian field isolate of the PRRS virus by using the
      E. coli. expression system. Finally, it was shown as possible to use the
      recombinant protein in indirect immune enzyme assay for the sake of detecting the
      antibodies to the PRRS virus.

PMID- 15164722
TI  - How PR firms use research to sell products.

PMID- 15164723
TI  - [Alcoholic cardiomyopathy (existence of cofactors of development: alcohol
      sensitivity and genetic factors)].

PMID- 15164724
TI  - Circulating TNF-alpha and its soluble receptors during experimental acute
      pancreatitis.
AB  - Clinical and experimental studies have shown increased concentrations of TNF
      alpha and its soluble receptors in serum of patients with acute pancreatitis. In
      this work, we have investigated the time-course of TNF-alpha and its soluble
      receptors during taurocholate-induced acute pancreatitis. In addition, since TNF
      alpha itself could mediate the shedding of its receptors, we have assessed the
      effect of inhibiting TNF-alpha production on the release of soluble TNF-alpha
      receptors in experimental acute pancreatitis. Our results indicate that soluble
      receptors are released in the early stages of the disease and this increase is
      concomitant with the release of TNF-alpha, which is mainly bound to specific
      proteins. The increased concentrations of its receptors strongly suggest that
      they could be these binding proteins. Inhibition of TNF-alpha generation with
      pentoxifylline abrogated the shedding of sTNF-alphaR1, but had no effect on sTNF
      alphaR2. This finding suggests that the shedding of sTNF-alphaR1 is induced by
      TNF-alpha itself, but in the case of sTNF-alphaR2, the shedding appears to be
      induced by another mechanism.

PMID- 15164725
TI  - HIV infection and advanced age emerging epidemiological, clinical, and management
      issues.
AB  - While the mean age of HIV/AIDS patients at first diagnosis is progressively
      rising, no updated epidemiological estimates, controlled clinical data, and
      randomized therapeutic trials, are available regarding clinical and laboratory
      response to antiretroviral therapy, safety of anti-HIV compounds and their
      associations, potential drug-drug interactions, short- and long-term toxicity,
      consequences on underlying disorders, or interactions with concomitant
      pharmacological regimens, in the elderly. The life expectancy of HIV-infected
      persons treated with highly active antiretroviral therapy (HAART) now
      approximates that of general population matched for age, while also AIDS
      definition itself has lost most of its epidemiological and clinical significance,
      thanks to the immunoreconstitution resulting from the large-scale use of potent
      HAART regimens. The increased survival of HIV-infected patients, the late
      recognition of other subjects with missed or delayed diagnosis are responsible
      for a further expected rise of mean age of HIV-infected individuals, so that the
      patient population aged 60-70 years or more is expected to increase in coming
      years. Unfortunately, the majority of therapeutic trials involving antiretroviral
      therapy, as well as antimicrobial chemoprophylaxis for AIDS-related opportunistic
      complications, have advanced age and/or concurrent end-organ disorders among main
      exclusion criteria, or the design of these studies does not allow to extrapolate
      data regarding older patients, compared with younger ones. The very limited data
      presently available seem to demonstrate that HAART has a virological efficacy in
      the elderly comparable with that of younger adults, but immunological recovery is
      often slower and blunted, although several studies clearly demonstrated that
      thymic function is preserved until late adult age. When facing an HIV-infected
      patient with advanced age, health care givers have to pay careful attention to
      eventual end-organ disorders, all possible pharmacological interactions,
      overlapping toxicity due to concurrent drug administration. All these issues may
      significantly interfere with HAART activity, patient's adherence to prescribed
      medications, and frequency and severity of untoward effects. The guidelines of
      antiretroviral therapy and those of treatment and prophylaxis of AIDS-related
      diseases deserve appropriate updates, paralleling the increasing mean age of HIV
      infected population. Moreover, epidemiological figures need an increased focus on
      older age, while clinical trials specifically targeting on the elderly population
      are mandatory to have reliable data on all aspects of HAART administration in
      advanced age.

PMID- 15164726
TI  - Cost analysis of endoscopic antireflux procedures: endoluminal plication vs.
      radiofrequency coagulation vs. treatment with a proton pump inhibitor.

PMID- 15164727
TI  - Antibiotic prophylaxis for GI procedure.

PMID- 15164728
TI  - Waldenstrom's macroglobulinemia of the GI tract.

PMID- 15164729
TI  - Organosulfur compounds from alliaceae in the prevention of human pathologies.
AB  - A strong association between elevated plasma low-density-lipoprotein (LDL) and
      the development of cardiovascular diseases (CVD) has been established. Oxidation
      of LDL (Ox-LDL) promotes vascular dysfunction, enhances the production and
      release of inflammatory mediators such as reactive oxygen species and contribute
      to the initiation and progression of atherosclerosis. In addition, Ox-LDL
      enhances the production and release of tumor necrosis factor (TNF-alpha),
      interleukin (IL)-6, arachidonic acid metabolites and nitric oxide (NO) that are
      responsible for various human pathologies including cancer. Organosulfur
      compounds (OSC) from alliaceae modulate the glutathione (GSH) redox cycle and
      inhibits NFkappa-B activation in human T cells. Furthermore, OSC bioactivities
      include antioxidant, antibacterial, anticarcinogenic, antiatherogenic,
      immunostimulatory, and liver protection potential.

PMID- 15164731
TI  - [Abdominal trauma. Injury oriented management].
AB  - Successful management of abdominal trauma is characterized by efficient emergency
      room work-up aimed at immediate determination of the prognosis by rational use of
      diagnostic techniques. The purposes of any conservative and/or surgical
      procedures are the preservation of organ function and low mortality and morbidity
      in multiply injured patients. State-of-the-art computed tomography with fast
      trauma scanning has become well accepted among patients with multiple trauma.
      Organ resections are becoming less common, except in the case of bowel injuries.
      The surgical treatment of hepatobiliary, splenic and large-vessel trauma is still
      challenging, as it involves the risk of life-threatening bleeding, while in the
      case of pancreatic and bowel injuries the challenge lies in the avoidance of
      septic complications. Interdisciplinary management of complex injuries with
      application of the "damage control" concept contributes to high-quality results
      in abdominal trauma.

PMID- 15164730
TI  - Plasma leptin concentration and change in bone density among elderly men and
      women: the Hertfordshire Cohort Study.
AB  - Several studies have shown an association between circulating leptin
      concentration and bone mineral density. but most studies are cross-sectional in
      design and report findings in women only. We per-formed a population-based
      longitudinal study relating baseline plasma leptin concentration to bone mass at
      the lumbar spine and femoral neck and to change in bone density at these sites
      over four years in a cohort of 302 men and women aged 60 75 years born and still
      resident in Hertfordshire, UK. Baseline plasma leptin concentration was strongly
      positively correlated with body mass index (men: r = 0.71, P 0.0001; women: r =
      0.79, P < 0.0001) and with bone mineral content,bone mineral density, and
      volumetric bone mineral density at all sites (r = 0.24-0.36, P < 0.001) in both
      sexes: associations with change in bone density were markedly weaker and
      inconsistent. Adjustment for adult lifestyle determinants of osteoporosis made
      little difference to our results, but the associations of leptin with bone mass
      were no longer significant after adjustment for body mass index. These results
      suggest that the relationship between plasma leptin and bone mass is similar in
      men and women and that it is mediated through the strong association of both
      variables with adiposity, rather than through a direct association of leptin on
      bone cell function.

PMID- 15164732
TI  - [The 16th spring meeting of the Japanese Society of Allergology. Gunma, Japan.
      May 12-14, 2004. Abstracts].

PMID- 15164734
TI  - Independence(TM) iBOT(TM) 3000 Mobility System: a stair-climbing wheelchair.
AB  - Independence (TM) iBOT(TM) 3000 is a wheelchair that may be used to climb stairs,
      elevate the user to standing adult eye level and cross uneven terrain. Limited
      evidence indicates that the device may offer more mobility and freedom to users
      than conventional wheelchairs. The iBOT may be difficult to manoeuvre indoors due
      to the seat height, but it operates well outdoors. The use of this technology is
      limited by the high cost of ownership and uncertain incremental benefit for
      users. While the device is not yet licensed for use in Canada, it is approved by
      the Food and Drug Administration for use in the US.

PMID- 15164733
TI  - [Cesarean section on maternal request: cons].

PMID- 15164735
TI  - A homeless man with maculopapular rash who died in Marseille, France.

PMID- 15164737
TI  - HIV/AIDS in China.

PMID- 15164738
TI  - Unreasonable publicity: how well does tort law protect the unwarranted disclosure
      of a person's HIV-positive status?

PMID- 15164739
TI  - Reproductive rights in Afghanistan: considerations of abortion regulation in
      light of the Afghan reconstruction process.

PMID- 15164740
TI  - Going beyond parents and institutional review boards in protecting children
      involved in nontherapeutic research.

PMID- 15164741
TI  - Genetic patents: gatekeeper to the promised cures.

PMID- 15164742
TI  - Assisted suicide and human rights.
AB  - The case of R (Pretty) v. Director of Public Prosecutions, gave the House of
      Lords the opportunity to comment on the issues surrounding the application of the
      European Convention on Human Rights to the crime of assisted suicide in the case
      of the terminally ill. A conservative approach was taken in relation to both this
      issue and indeed in relation to the possibilities of judicial control of the Law
      Officers of the Crown.

PMID- 15164743
TI  - From conception until birth: exploring the maternal duty to protect fetal health.

PMID- 15164744
TI  - Contraceptive coverage laws: eliminating gender discrimination or infringing on
      religious liberties?

PMID- 15164745
TI  - Conceiving harm: disability discrimination in assisted reproductive technologies.
AB  - Applying the Americans with Disabilities Act (ADA) to denials of treatment by
      assisted reproductive technology (ART) practitioners raises particularly
      challenging legal and ethical issues. On the one hand, the danger that physicians
      will inappropriately deny treatment to patients with disabilities is especially
      worrisome in the context of ARTs, given the widespread stigma associated with
      reproduction by individuals with disabilities. On the other hand, patients'
      disabilities may sometimes have potentially devastating implications for any
      child resulting from treatment, including the possibility that the child will be
      born with life-threatening or seriously debilitating impairments. Some physicians
      have strong ethical objections to helping patients become pregnant in the face of
      such risks. In this Article, Professor Coleman develops a framework for applying
      the ADA to disability-based denials of ARTs that addresses these competing
      considerations. In recognizing risks to the future child as a potential defense
      to a disability discrimination claim, Professor Coleman rejects the view of some
      commentators that such risks are relevant to reproductive decisions only if the
      child is likely to suffer so much that he or she would prefer not to exist.
      Instead, he proposes that, when a patient's disabilities create significant risks
      to the future child, the question should not be whether the child's life is
      likely to be so awful that nonexistence would be preferable, but how the risks
      and benefits of the requested treatment compare to those associated with other
      available reproductive and parenting options. Professor Coleman provides a
      theoretical justification for adopting this comparative framework, and examines
      how ADA precedents developed in other contexts should be applied to decisions
      about ARTs.

PMID- 15164746
TI  - Human reproductive cloning: a policy framework for South Africa.

PMID- 15164747
TI  - King Solomon in the age of assisted reproduction.

PMID- 15164748
TI  - Until life support do us part: a spouse's limited ability to terminate life
      support for an incompetent spouse with no hope of recovery.

PMID- 15164749
TI  - Ethical postures of futility and California's Uniform Health Care Decisions Act.

PMID- 15164750
TI  - Not without my father: the legal status of the posthumously conceived child.

PMID- 15164752
TI  - [A clinical scale for determining the sensitivity of MECP2 genetic analysis].

PMID- 15164751
TI  - Misrepresentation of research publications among orthopedic surgery fellowship
      applicants: a comparison with documented misrepresentations in other fields.
AB  - Study Design. A retrospective study was used to review fellowship applications
      over 3 years. Objectives. To assess the prevalence of research misrepresentation
      in orthopedic fellowship applications, and to compare such activity between
      subspecialties (e.g. spine, sports, hand). Summary of Background Data.
      Competition for orthopedic surgery fellowships is intense. The applicant pool
      includes orthopedic, plastic, and general surgeons, as well as neurosurgeons.
      Residency and fellowship training programs in other disciplines have documented
      shocking levels of misrepresentation in the curriculum vitae of prospective
      applicants. However, no study has looked at orthopedic residents applying for
      subspecialty fellowship programs. Methods. A retrospective analysis investigated
      280 applications for fellowship positions in the department of orthopedic surgery
      at the authors' academic institution from 1996 to 1998 inclusively. To allow for
      press and publication delays, a minimum 24-month follow-up period was instituted.
      The listings of applicants' research publications were analyzed for evidence of
      misrepresentation through an exhaustive literature search. Only the most obvious
      confirmable discrepancies were labeled as misrepresentations. The results then
      were compared with those found in studies conducted in other fields:
      gastroenterology fellowship, emergency medicine residency, pediatric residency,
      dermatology residency, orthopedic residency, and medical faculty applications.
      Results. Among 280 (54%) applicants for orthopedic surgery candidates, 151
      claimed journal publications. It was found that 16 (10.6%) of these 151
      applicants had misrepresented their citations. This rate was highest in spine
      fellowship applicants (20%). However, considering the numbers available, this was
      not significantly different among the various subspecialty fellowship applicants
      (P>0.1). In addition, various demographic data did not correlate with the rate of
      misrepresentation (P>0.1). These results are comparable with those reported in
      other medical fields (P>0.1). Conclusions. Misrepresentation occurs in orthopedic
      fellowship applications at a rate comparable with that observed in other fields.
      This rate is not different among the various subspecialties in orthopedics.
      Policies that may lessen the incidence of falsification on curriculum vitae
      should be instituted in an attempt to curb such activity.

PMID- 15164753
TI  - Viewpoint: ethics in advertising.

PMID- 15164754
TI  - Henk van den Bosch: chemist and biochemist.
AB  - Henk van den Bosch is a native of The Netherlands and recently retired from his
      position as Professor at Utrecht University. This article summarizes the many
      scientific achievements of Dr. van den Bosch. He enjoys an international
      reputation for his research on phospholipases A, cardiolipin biosynthesis in
      eukaryotes, lysophospholipases, phosphatidylcholine biosynthesis for lung
      surfactant, plasmalogen biosynthesis in peroxisomes, diagnosis of peroxisomal
      disorders and most recently his work on alkyl-dihydroxyacetone phosphate
      synthase. During his research career Henk van den Bosch published approximately
      280 articles and presented 110 invited lectures.

PMID- 15164755
TI  - Increased accumulation of the glycoxidation product Nepsilon
      (carboxymethyl)lysine in hearts of diabetic patients: generation and
      characterisation of a monoclonal anti-CML antibody.
AB  - Heart failure is a condition closely linked to diabetes. Hyperglycaemia amplifies
      the generation of a major advanced glycation end product Nepsilon
      (carboxymethyl)lysine (CML), which has been associated with the development of
      vascular and inflammatory complications. An increased accumulation of CML in
      hearts of diabetic patients may be one of the mechanisms related to the high risk
      of heart failure. Therefore, we investigated the localization of CML in diabetic
      hearts. To investigate the presence and accumulation of CML in tissues, a
      monoclonal anti-CML antibody was generated and characterised. With this novel
      monoclonal antibody against CML, the localization of CML was investigated by
      immunohistochemistry, in heart tissue of controls (n = 9) and heart tissue of
      diabetic patients (n = 8) without signs of inflammation or infarction. In
      addition, in the same subjects we studied the presence of CML in renal and lung
      tissues. CML staining was approximately sixfold higher in hearts from diabetic
      patients as compared to control hearts (2.0 +/- 0.3 and 0.3 +/- 0.2 A.U.,
      respectively, P < 0.01). CML deposition was localized in the small
      intramyocardial arteries in endothelial cells and smooth muscle cells, but not in
      cardiomyocytes. These arteries did not show morphological abnormalities. The
      intensity of staining between arteries at the epicardial, midcardial and
      endocardial side did not vary significantly within patients. In renal tissues,
      CML staining was most prominent in tubules and in atherosclerotic vessels,
      without differences in intensity between controls and diabetic patients. In non
      infected lungs, no CML was detected. In conclusion, CML adducts are abundantly
      present in small intramyocardial arteries in the heart tissue of diabetic
      patients. The accumulation of CML in diabetic hearts may contribute to the
      increased risk of heart failure in hyperglycaemia.

PMID- 15164756
TI  - Administration of phosphatidylcholine-cholesterol liposomes partially
      reconstitutes fat absorption in chronically bile-diverted rats.
AB  - BACKGROUND AND AIMS: Intestinal bile deficiency in cholestatic patients leads to
      fat malabsorption. We addressed the potency of model bile, bile salts and
      phosphatidylcholine (PC)-cholesterol (CH) liposomes to reconstitute fat
      absorption in permanently bile-diverted (BD) rats. METHODS: The plasma appearance
      of 13C-labeled palmitic acid (13C-16:0) and linoleic acid (13C-18:2) was
      determined after their enteral administration to BD or to control rats with an
      intact enterohepatic circulation (EHC) (13C-16:0 and 13C-18:2 dissolved in 25%
      olive oil-75% medium chain triacylglycerol oil mixture). BD rats were
      intraduodenally infused with buffer, model bile [consisting of 60 mM taurocholate
      (TC), 8 mM PC and 1 mM CH], buffer with TC, buffer with PC and CH liposomes, or
      buffer with lyso-PC and CH. RESULTS: Plasma concentrations of 13C-16:0 and 13C
      18:2 were consistently three- to eightfold higher in control rats than those in
      buffer-infused BD rats (P < 0.01). ID administration of either model bile or TC
      to BD rats restored plasma appearance of 13C-fatty acids at least to
      concentrations observed in control rats. Administration of PC + CH liposomes to
      BD rats partially reconstituted the plasma appearance of 13C-16:0, but did not
      affect that of 13C-18:2. Compared with control rats, the area under the curve
      (AUC) of plasma 13C-16:0 concentrations was 13.0 +/- 6.9% in buffer-infused rats
      and 40.9 +/- 3.1% in liposome-infused rats (P < 0.005). CONCLUSIONS: Enteral
      administration of PC + CH liposomes to BD rats partially corrects the absorption
      of palmitic acid. Present data suggest that administration of PC + CH liposomes
      could enhance fat absorption in clinical conditions of cholestasis in which bile
      salt supplemention is contraindicated.

PMID- 15164757
TI  - Inhibition of phosphatidylcholine synthesis is not the primary pathway in
      hexadecylphosphocholine-induced apoptosis.
AB  - The anticancer drug hexadecylphosphocholine (HePC), an alkyl-lysophospholipid
      analog (ALP), has been shown to induce apoptosis and inhibit the synthesis of
      phosphatidylcholine (PC) in a number of cell lines. We investigated whether
      inhibition of PC synthesis plays a major causative role in the induction of
      apoptosis by HePC. We therefore directly compared the apoptosis caused by HePC in
      CHO cells to the apoptotic process in CHO-MT58 cells, which contain a genetic
      defect in PC synthesis. HePC-provoked apoptosis was found to differ substantially
      from the apoptosis observed in MT58 cells, since it was (i) not accompanied by a
      large decrease in the amount of PC and diacylglycerol (DAG), (ii) not preceded by
      induction of the pro-apoptotic protein GADD153/CHOP, and (iii) not dependent on
      the synthesis of new proteins. Furthermore, lysoPC as well as
      lysophosphatidylethanolamine (lysoPE) could antagonize the apoptosis induced by
      HePC, whereas only lysoPC was able to rescue MT58 cells. HePC also induced a
      rapid externalisation of phosphatidylserine (PS). These observations suggest that
      inhibition of PC synthesis is not the primary pathway in HePC-induced apoptosis.

PMID- 15164759
TI  - Scott syndrome, a bleeding disorder caused by defective scrambling of membrane
      phospholipids.
AB  - Normal quescent cells maintain membrane lipid asymmetry by ATP-dependent membrane
      lipid transporters, which shuttle different phospholipids from one leaflet to the
      other against their respective concentration gradients. When cells are
      challenged, membrane lipid asymmetry can be perturbed resulting in exposure of
      phosphatidylserine [PS] at the outer cell surface. Translocation of PS from the
      inner to outer membrane leaflet of activated blood platelets and platelet-derived
      microvesicles provides a catalytic surface for interacting coagulation factors.
      This process is dramatically impaired in Scott syndrome, a rare congenital
      bleeding disorder, underscoring the indispensible role of PS in hemostasis. This
      also testifies to a defect of a protein-catalyzed scrambling of membrane
      phospholipids. The Scott phenotype is not restricted to platelets, but can be
      demonstrated in other blood cells as well. The functional aberrations observed in
      Scott syndrome have increased our understanding of transmembrane lipid movements,
      and may help to identify the molecular elements that promote the collapse of
      phospholipid asymmetry during cell activation and apoptosis.

PMID- 15164758
TI  - Inhibition of Rho modulates cytokine-induced prostaglandin E2 formation in renal
      mesangial cells.
AB  - Stimulation of rat mesangial cells for 24 h with interleukin-1beta (IL- 1beta)
      plus forskolin (Fk) leads to a marked increase in prostaglandin E2 (PGE2)
      synthesis. This effect is further enhanced by the small G-protein Rho inhibitor
      toxin A. A similar increase in PGE2 formation is obtained with Y27632, a Rho
      dependent kinase inhibitor, and with lovastatin, a hydroxymethylglutaryl-coenzyme
      A inhibitor which depletes cells from geranylgeranyl moieties and thus blocks Rho
      activation. In parallel to the increased PGE2 synthesis, a potentiation of IL
      1beta-induced secretory group IIA phospholipases A2 (sPLA2-IIA) protein
      expression also occurs by Rho inhibition. However, only toxin A triggers an
      increased sPLA2-IIA activity consistent with the elevated levels of protein
      expression, whereas Y27632 and lovastatin rather reduced IL-1beta-induced sPLA2
      IIA activity. In vitro activity studies reveal that Y27632 and lovastatin can
      directly block sPLA2-IIA enzyme activity in a concentration-dependent manner.
      Interestingly, in the absence of IL-1beta/Fk stimulation and the lack of sPLA2
      IIA protein expression, all Rho inhibitors exert a small but significant increase
      in PGE2 formation suggesting that additional PLA2s or downstream enzymes like
      cyclooxygenases or prostaglandin synthases may be activated by Rho inhibitors.
      Western blot analyses of toxin A-, Y27632- and lovastatin-stimulated cells reveal
      that the cytosolic group IV PLA2 (cPLA2) and the cytosolic PGE2 synthase (cPGES),
      but not the sPLA2-IIA, cyclooxygenase-2 or the microsomal PGE2 synthase (mPGES),
      are upregulated compared to unstimulated cells. Furthermore, the Rho inhibitors
      induced arachidonic acid release from intact cells which is blocked by the cPLA2
      inhibitor methyl arachidonyl fluorophosphonate (MAFP). In summary, these data
      show that inhibition of the small G-protein Rho, either by toxin A, lovastatin,
      or Y27632, exert a dual effect on mesangial cells: (i) in the absence of an
      inflammatory stimulus it activates the constitutive cPLA2 and cPGE2 synthase and
      generates low amount of PGE2. (ii) In the presence of inflammatory cytokines it
      potentiates sPLA2-IIA expression and subsequent PGE2 formation. In addition, we
      identified lovastatin and Y27632 as direct inhibitors of sPLA2-IIA in a cell-free
      system.

PMID- 15164760
TI  - Knock down of cytosolic phospholipase A2: an antisense oligonucleotide having a
      nuclear localization binds a C-terminal motif of glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - We have previously shown that an antisense, effective in the knock down of
      cytosolic phospholipase A2 (cPLA2), localizes mainly in the nucleus of human
      endothelial cells and monocytes and that glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) is involved in its nuclear localization. In this study, we clarify how
      GAPDH participates in the nuclear localization of this antisense
      oligodeoxynucleotide (ODN) directed against cPLA2 mRNA. A central TAAAT motif
      providing specificity and high affinity binding was assumed to interact with the
      enzyme Rossmann fold region on the basis of competition to this site by NAD+. To
      asses whether the TAAAT motif interacts directly with the enzyme Rossmann fold
      region, we evaluated the binding to GAPDH of different oligonucleotides and the
      effect of competitors such as NAD+, NADH, mononucleotides, DNA, polyribonucleic
      acids and polyanions. We found that the dissociation constant for TAAAT
      containing oligonucleotides was three--to fivefold higher with respect to oligo
      not containing this motif. By covalently linking 32P-labeled cPLA2p(N)16 to GAPDH
      and after executing hydrolysis with hydroxylamine, the labeling was exclusively
      found in the C-terminal domain (aa 286-334). These results indicate that the
      antisense oligonucleotide interacts with a site not having a defined function but
      which can be negatively allosterically regulated when NAD+ or polynucleotides are
      bound to Rossmann fold.

PMID- 15164761
TI  - Attenuation of lipid peroxidation by antioxidants in rat-1 fibroblasts:
      comparison of the lipid peroxidation reporter molecules cis-parinaric acid and
      C11-BODIPY(581/591) in a biological setting.
AB  - Lipid peroxidation is a major factor in the pathogenesis of many disease states.
      To detect the initial stages of lipid peroxidation or evaluate antioxidant
      efficacy, cis-parinaric acid (cis-PnA) has been successfully used and thoroughly
      validated. However, cis-PnA is not very well suited for medium throughput
      screening of antioxidants in living cells. We recently introduced and validated a
      lipid peroxidation reporter molecule, C11-BODIPY(581/591). To further explore
      this probe, we evaluated the protective effect of 12 natural antioxidants in rat
      1 fibroblasts subjected to 50 microM cumene-hydroperoxide using both probes. The
      same pecking order for the individual antioxidant efficacies was obtained: alpha
      tocopherol approximately gamma-tocopherol > quercetin approximately lycopene >
      kaempferol > palm oil > hydroxy-tyrosol > > alpha-carotene = beta-carotene =
      lutein = tyrosol = chlorogenic acid. This validates the accuracy of the C11
      BODIPY(581/591) method and shows that this assay is an accurate and highly
      flexible method for indexing lipid peroxidation or determining antioxidant
      efficacy in living cells in a medium throughput scenario. The antioxidant
      efficacy was compared with their one-electron reduction potential, hydrophobicity
      and Trolox C equivalent antioxidant capacity. Our results show that although
      these parameters are valuable for determining structure-function relationships,
      they have limited predictive value for antioxidant efficacy in vivo.

PMID- 15164762
TI  - Overexpression of phosphatidylinositol transfer protein beta in NIH3T3 cells has
      a stimulatory effect on sphingomyelin synthesis and apoptosis.
AB  - Phosphatidylinositol transfer proteins (PI-TPs) consist of two isoforms (PI
      TPalpha and PI-TPbeta), which differ in phospholipid transfer properties and
      intracellular localization. Both PI-TP isoforms are substrates for protein kinase
      C and contain a minor phosphorylation site (Ser166 in PI-TPalpha; Ser165 in PI
      TPbeta). Only PI-TPbeta contains a major phosphorylation site at Ser262, which
      must be phosphorylated for PI-TPbeta to be associated with the Golgi. The PI-TP
      isoforms are completely conserved between mammals. Although their function is
      still not clear, their importance follows from knock-out studies, showing that
      mice lacking PI-TPalpha die soon after birth and that embryonic stems cells
      lacking PI-TPbeta cannot be generated [Mol. Biol. Cell 13 (2002) 739]. We
      determined the levels of the PI-TP isoforms in various mouse tissues by
      immunoblotting. PI-TPalpha is present in all tissues investigated, with highest
      levels in brain (167 ng/100 microg total protein). The levels of PI-TPbeta are 50
      100 times lower than those of PI-TPalpha, with relatively high levels found in
      liver and brain (1.2 and 1.8 ng/100 microg of total protein, respectively). In
      contrast to NIH3T3 cells overexpressing PI-TPalpha, cells overexpressing PI
      TPbeta (SPIbeta cells) were able to maintain steady-state levels of sphingomyelin
      in plasma membrane under conditions where this lipid is degraded by exogenous
      sphingomyelinase. This process of rapid sphingomyelin replenishment is dependent
      on PI-TPbeta being associated with the Golgi as cells overexpressing a mutant PI
      TPbeta in which the major phosphorylation site is replaced (PI-TPbeta(S262A)
      behave as wild-type NIH3T3 cells. Since the SPIbeta cells display a decreased
      growth rate (35 h as compared to 21 h for wtNIH3T3 cells), we have investigated
      the sensitivity of these cells towards UV-induced apoptosis. We have found that
      the SPIbeta cells, but not the cells overexpressing PI-TPbeta(S262A), are very
      sensitive. We are currently investigating whether a relationship exists between
      PI-TPbeta being involved in maintaining plasma membrane sphingomyelin levels and
      the enhanced sensitivity towards apoptosis.

PMID- 15164763
TI  - Differential binding of ceramide to MEKK1 in glomerular endothelial and mesangial
      cells.
AB  - Previously, we have shown that ceramide is able to directly bind to and activate
      c-Raf and to trigger the downstream classical mitogen-activated protein kinase
      (MAPK/ERK) cascade in glomerular mesangial cells [Proc. Natl. Acad. Sci. USA 93
      (1996) 6959]. In this study, we show that ceramide acts differently in glomerular
      endothelial cells in that treatment of endothelial cells with exogenous ceramide
      leads to a potent activation of the stress-activated protein kinase (SAPK/JNK)
      cascade but not to an activation of the classical ERK cascade. A similar effect
      was observed with the inflammatory cytokines TNFalpha and IL-1beta, which
      activate a sphingomyelinase and thereby increase intracellular ceramide levels.
      The activation of JNKs as shown by c-Jun phosphorylation assays was paralleled by
      increased phosphorylation of the two JNK isoforms, p45 and p54. In addition, also
      the activator of JNKs, SEK1, was found to be increasingly phosphorylated by
      exogenous ceramide as well as by TNFalpha. In contrast, dihydroceramide had no
      effect on JNK or SEK1 phosphorylation. To see whether ceramide directly binds to
      MEKK1, which is the c-Raf analog in the SAPK cascade, a radioiodinated
      photoaffinity labeling analogue of ceramide, (N-[3-[[[2-(125I)iodo-4-[3
      (trifluoromethyl)-3H-diazirin-3-yl]benzyl]oxy]-carbonyl] propanoyl]-D-erythro
      sphingosine) ([125I]TID-ceramide) was used. Stimulation of endothelial cells with
      this [125I]TID-ceramide for 5 min followed by a short photolysis defined MEKK1 as
      a direct target of ceramide. With the same method, protein kinase C-alpha (PKC
      alpha) was identified as a ceramide target. In contrast, no binding to c-Raf or
      the MEKK1 activator p65-PAK could be detected. A direct binding of ceramide to
      MEKK1 was also confirmed by affinity chromatography using a ceramide-coupled
      sepharose column. Furthermore, the ceramide-activated SAPK/JNK cascade is clearly
      involved in the mechanism of apoptosis, since in the presence of a JNK inhibitor,
      ceramide-induced DNA fragmentation is significantly reduced. In summary, we have
      shown that ceramide potently activates the SAPK cascade but not the ERK cascade
      in endothelial cells, which contrasts to mesangial cells where ceramide activates
      the ERK pathway and has only a minor effect on the SAPK cascade. Regarding the
      direct target of ceramide binding and action in endothelial cells, we identified
      MEKK1 as a further member of the growing family of ceramide-activated protein
      kinases.

PMID- 15164764
TI  - Structure-activity relationship of diacylglycerol kinase theta.
AB  - Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol
      (DAG) to phosphatidic acid (PA). Among the nine mammalian isotypes identified,
      DGKtheta is the only one with three cysteine-rich domains (CRDs) (instead of two)
      in its N-terminal regulatory region. We previously reported that DGKtheta binds
      to and is negatively regulated by active RhoA. We now report that RhoA strongly
      binds to the C-terminal catalytic domain, which would explain its inhibition of
      DGK activity. To help finding a physiological function of DGKtheta, we further
      determined its activity in vitro as a function of 15 different truncations and
      point mutations in the primary structure. Most of these alterations, located
      throughout the protein, inactivated the enzyme, suggesting that catalytic
      activity depends on all of its conserved domains. The most C-terminal CRD is
      elongated with a stretch of 15 amino acids that is highly conserved among DGK
      isotypes. Mutation analysis revealed a number of residues in this region that
      were essential for enzyme activity. We suggest that this CRD extension plays an
      essential role in the correct folding of the protein and/or in substrate
      presentation to the catalytic region of the protein.

PMID- 15164765
TI  - Dimethylethanolamine does not prevent liver failure in phosphatidylethanolamine N
      methyltransferase-deficient mice fed a choline-deficient diet.
AB  - Mice that lack phosphatidylethanolamine-N-methyltransferase (PEMT) and are fed a
      choline-deficient (CD) diet suffer severe liver damage and do not survive. Since
      phosphatidyldimethylethanolamine (PDME) has physical properties similar to those
      of phosphatidylcholine (PC), we hypothesized that dimethylethanolamine (DME)
      would be converted into PDME that might substitute for PC, and therefore abrogate
      the liver damage in the Pemt -/- mice fed a CD diet. We fed Pemt -/- mice either
      a CD diet, a CD diet supplemented with choline, or a CD diet supplemented with
      DME (CD + DME). Pemt -/- mice fed the CD diet developed severe liver failure by 4
      days while CD + DME-fed mice developed severe liver failure by 5 days. The
      hepatic PC level in choline-supplemented (CS) mice was 67 +/- 4 nmol/mg protein,
      whereas the PC content was reduced in CD- and CD + DME-fed mice (49 +/- 3 and 30
      +/- 3 nmol/mg protein, respectively). Upon supplementation of the CD diet with
      DME the amount of hepatic PDME was 81 +/- 9 nmol/mg protein so that the hepatic
      content of PC + PDME combined was 111 nmol/mg protein. Moreover, plasma
      apolipoprotein B100 and Al levels were markedly lower in mice fed the CD + DME
      diet compared to mice fed the CS diet, as was the plasma content of PC. Thus,
      despite replacement of the deficit in hepatic PC with PDME in Pemt -/- mice fed a
      CD diet, normal liver function was not restored. We conclude that although PC and
      PDME exhibit similar physical properties, the three methyl groups of choline are
      required for hepatic function in mice.

PMID- 15164766
TI  - Activation of cytosolic phospholipase A2 in Her14 fibroblasts by hydrogen
      peroxide: a p42/44(MAPK)-dependent and phosphorylation-independent mechanism.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of
      diseases as well as various normal cellular processes. It has been suggested that
      ROS function as mediators of signal transduction, given that they can mimic
      growth factor-induced signaling. The ROS H2O2 has been reported to activate
      phospholipase A2 (PLA2) and, therefore, we investigated if and through which
      pathway ROS activate cytosolic PLA2 (cPLA2) in Her14 fibroblasts. cPLA2 was
      activated concentration-dependently by H2O2 in a transient manner. In addition,
      the lipophilic cumene hydroperoxide was shown to induce cPLA2 activity in the
      same manner. H2O2-induced cPLA2 activity in Her14 cells was partially
      phosphorylation-dependent, which was mediated through the Raf-MEK-p42/44(MAPK)
      pathway and occurred partially through a phosphorylation-independent mechanism.
      ROS can lead to changes in the (micro) viscosity of membranes due to the presence
      oxidized lipids, thereby increasing the substrate availability for cPLA2. In
      support of this, treatment of Her14 cells with H2O2 induced lipid peroxidation
      time-dependently as determined from degradation of lipid arachidonate and
      linoleate and the formation of aldehydic degradation products. Furthermore, H2O2
      induced translocation of cPLA2 to the membrane fraction in a calcium-independent
      fashion, with a concomitant increase in cPLA2 activity. Collectively, the results
      suggest that oxidative stress-induced cPLA2 activity is partially phosphorylation
      dependent and is further increased due to increased substrate availability by the
      action of ROS on membranes.

PMID- 15164768
TI  - Uptake and remodeling of exogenous phosphatidylethanolamine in E. coli.
AB  - The fate of exogenous short-chain analogues of phosphatidylethanolamine and
      phosphatidylserine was studied in a deep-rough derivative of E. coli mutant
      strain AD93 that cannot synthesize phosphatidylethanolamine de novo. Using mass
      spectrometry, it was shown that dicaproyl(di 6:0)-phosphatidylethanolamine is
      extensively remodeled, eventually adopting the phosphatidylethanolamine species
      profile of the parental wild-type strain of AD93. Dicaproyl-phosphatidylserine
      was decarboxylated to form phosphatidylethanolamine, and yielded a species
      profile, which strongly resembled that of the introduced
      phosphatidylethanolamine. This demonstrates transport of phosphatidylserine to
      the cytosolic leaflet of the inner membrane. The changes of the species profile
      of phosphatidylethanolamine indicate that the short-chain phospholipids are most
      likely remodeled via two consecutive acyl chain substitutions, and at least part
      of this remodeling involves transport to the inner membrane.

PMID- 15164767
TI  - Phenotype of palmitic acid transport and of signalling in alveolar type II cells
      from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma.
AB  - Based on the assumption that fatty-acid-binding proteins (FABPs) of the epidermal
      type (E-FABP) and heart-type (H-FABP) in murine alveolar type II (TII) cells
      mediate the synthesis of dipalmitoyl phosphatidylcholine (DPPC), the main
      surfactant phospholipid, we analysed TII cells isolated from wild-type (wt) and
      E/H-FABP double-knockout (double-ko) mice. Application of labelled palmitic acid
      to these cells revealed a drop in uptake, beta-oxidation, and incorporation into
      neutral lipids and total phosphatidylcholine (PC) of TII cells from double-ko
      mice. Whereas incorporation of labelled palmitic acid into DPPC remained
      unchanged, degradation studies demonstrated a substantial shift in DPPC synthesis
      from de novo to reacylation. In addition, increased expression of mRNAs and
      proteins of caveolin-1 and PPARgamma, and an increase of the mRNA encoding fatty
      acid translocase (FAT) was observed in the double-ko phenotype. As caveolin-1
      interacted with PPARgamma, we assumed that FAT, caveolin-1, and PPARgamma form a
      signalling chain for fatty acid or drug. Consequently, PPARgamma-selective
      pioglitazone was added to the diet of double-ko mice. We found that further
      activation of PPARgamma could 'heal' the E/H-FABP double-ko effect in these TII
      cells as transport and utilisation of labelled palmitic acid restored a wt
      phenocopy. This indicated that E-FABP and/or H-FABP are involved in the mediation
      of DPPC synthesis in wt TII cells.

PMID- 15164769
TI  - The ABC's of Group IV cytosolic phospholipase A2.
AB  - The three known human Group IV phospholipase A2 (PLA2) paralogs, Group IVA, IVB
      and IVC, were overexpressed in Sf9 insect cells using the baculovirus expression
      system. An endogenous, calcium-independent PLA2 activity was identified in the
      insect cell lysates, which can be inhibited by bromoenol lactone (BEL). The Group
      IV PLA2 enzymes were characterized in overexpressing insect cell lysates in the
      presence of BEL, enabling their differentiation from the endogenous PLA2
      activity. Group IVC PLA2 was found to have significant lysophospholipase
      activity, while Group IVB PLA2 did not. Of the three paralogs, only the Group IVA
      PLA2 shows enhanced activity in the presence of PIP2, which enables its
      differential detection in cell homogenates. RT-PCR was used to demonstrate the
      presence of all three enzymes in human U937 and human WISH cells, while only
      Group IVA and Group IVB PLA2 were detected in murine P388D1 cells and human
      astrocytes at the mRNA level.

PMID- 15164770
TI  - Functions and biosynthesis of plasmalogens in health and disease.
AB  - Plasmalogens (1-O-alk-1'-enyl-2-acyl glycerophospholipids) constitute a special
      class of phospholipids characterized by the presence of a vinyl-ether bond at the
      sn-1 position. Although long considered as biological peculiarities, interest in
      this group of phospholipids has grown in recent years, thanks to the realization
      that plasmalogens are involved in different human diseases. In this review, we
      summarize the current state of knowledge with respect to the enzymatic synthesis
      of plasmalogens, the characteristic topology of the enzymes involved and the
      biological roles that have been assigned to plasmalogens.

PMID- 15164771
TI  - Post-herniographic abdominal pain syndrome.
AB  - PURPOSE: To disclose the frequency of abdominal pain that led to post-procedure
      hospitalization and the outcome of this major complication. MATERIAL AND METHODS:
      576 patients who had undergone herniography during a 13-year period were
      retrospectively analysed. RESULTS: Nine out of 576 patients (1.6%) undergoing
      herniography with an iodine contrast medium developed abdominal pain. The pain
      resolved within 24 h in 6 patients while 3 patients had pain for up to 3 days.
      CONCLUSION: Patients who present with this pain syndrome thus only need careful
      clinical observation until asymptomatic, with no need for laparotomy or X-ray
      examination. Prior to herniography, the patients should be informed about this
      potential complication.

PMID- 15164773
TI  - Intermittent hepatic artery antibiotic infusion therapy for pyogenic hepatic
      abscess.
AB  - PURPOSE: To study the efficacy and problems associated with intermittent hepatic
      artery antibiotic infusion therapy for pyogenic hepatic abscess. MATERIAL AND
      METHODS: The material comprised eight patients with pyogenic hepatic abscess in
      whom percutaneous drainage could not be performed and intravenous administration
      of antibiotics was ineffective. An injection catheter was introduced into the
      common hepatic artery. Almost the same dose of antibiotics as with intravenous
      administration was infused intra-arterially 2-4 times per day. RESULTS: A
      therapeutic effect was achieved in six of the eight cases. In these 6 cases, the
      mean period of intra-arterial infusion was 10.8 days, while the mean period of
      catheter placement was 14.7 days. Using broad spectrum antibiotics, the
      therapeutic effect was obtained regardless of the numbers, morphologic
      characteristics, and differences in location of the abscesses. No significant
      complications were noted except in one case of splenic infarction. CONCLUSION:
      Intermittent hepatic artery antibiotic infusion therapy is useful as an
      alternative therapeutic procedure for pyogenic hepatic abscess in which
      percutaneous drainage cannot be performed and intravenous administration of
      antibiotics is ineffective.

PMID- 15164772
TI  - Radiological spectrum of late sequelae of corrosive injury to upper
      gastrointestinal tract. A pictorial review.
AB  - PURPOSE: To evaluate the radiological spectrum of sequelae of corrosive acid and
      alkali injury to the upper gastrointestinal (GI) tract using barium contrast
      examination. MATERIAL AND METHODS: Barium contrast radiographic films of 155
      patients with a history of corrosive ingestion, acid in 120 and alkali in 35
      patients with grade 2b and 3 injury on initial endoscopy, were retrospectively
      evaluated. Barium contrast examination of the upper GI tract was performed in the
      course of follow-up, beyond 3 weeks of corrosive ingestion. RESULTS: The
      esophagus was involved in 131 patients and the stomach in 74. Fifty patients had
      simultaneous involvement of esophagus and stomach. Radiological findings in the
      esophagus were solitary or multiple strictures of varying length, intramural
      pseudodiverticula, and carcinoma in long-standing corrosive injury. The stomach
      showed cicatrization, predominantly involving the antrum, linitis plastica type
      deformity with multiple pseudodiverticula. There was no difference in the
      radiological findings as to the type of corrosive ingested. CONCLUSION: Barium
      examination of the upper GI tract is useful in the evaluation of late sequelae of
      corrosive injury (acid/alkali). There was no difference in the radiological
      findings as to the type of corrosive ingested. Thus, contrary to general belief,
      we found that acid and alkali damage both the esophagus and the stomach with
      equal degree of severity.

PMID- 15164774
TI  - Magnetic resonance imaging of metaplastic carcinoma of the breast: sonographic
      and pathologic correlation.
AB  - Metaplastic carcinoma of the breast is a rare disease. We describe the MRI
      findings with the correlative sonographic and pathologic features of two cases.
      On MRI, T2-weighted images demonstrate a relatively well-defined mass with high
      signal intensity cystic components. Dynamic enhancement subtraction images showed
      an early enhancing and delayed washout peripheral rim and non-enhancing internal
      components. A microlobulated, isoechogenic mass with cystic components was seen
      sonographically, and was histopathology related to necrosis and cystic
      degeneration. Although these features are not unique, metaplastic carcinoma
      should be included in the differential diagnosis for breast masses.

PMID- 15164775
TI  - Treatment of long superficial femoral artery occlusions with excimer laser
      angioplasty: long-term results after 48 months.
AB  - PURPOSE: To evaluate clinical and hemodynamical long-term results after laser
      angioplasty of long occlusions of the superficial femoral artery (SFA). MATERIAL
      AND METHODS: In a prospective trial of 452 patients with long occlusions of the
      SFA, excimer percutaneous transluminal laser angioplasty (PTLA) for
      recanalization was applied. The average occlusion length of the SFA was 25.5 cm
      (range 16-38 cm). The recanalization attempt was done with the crossover
      technique in 398 patients, in 36 patients with the antegrade technique and in
      another 18 patients with the transpopliteal technique. RESULTS: The application
      of laser angioplasty demonstrated a successful recanalization of the SFA in
      386/452 patients (85.5%). Recanalization with PTLA was not possible in 66
      patients (14.5%). The main reason for the unsuccessful PTLAs was obstructing
      calcified material (n = 28) resistant to PTLA application. After a follow-up
      period of 48 months there was a primary, primary-assisted, and secondary patency
      rate of 22.3%, 40.9%, and 43.2%, respectively. CONCLUSION: Laser angioplasty of
      long occlusions of the SFA is a feasible procedure with a low failure rate. Long
      term results are promising, but additional interventions are required in most
      patients if a patency rate of 43.2% is to be achieved after 4 years.

PMID- 15164776
TI  - Rapid-sequence phosphorus-31 magnetic resonance spectroscopy of the human heart
      using a 1.5-T clinical system.
AB  - PURPOSE: To compare a 'standard' slow phosphorus-31 magnetic resonance
      spectroscopy (31P-MRS) sequence with two faster sequences in phantoms and healthy
      volunteers using a 1.5-T clinical system. MATERIAL AND METHODS: Complete 3D
      localization was performed using a 2D phosphorus chemical-shift imaging sequence
      in combination with 30-mm axial slice-selective excitation. Two 31P-MRS rapid
      sequences (RS8-4: 8 x 8 phase-encoding, with an average of 4 acquisitions, and
      RS16-1: 16 x 16 phase-encoding, 1 acquisition) were compared with the standard
      sequence (StdP: 16 x 16 phase-encoding, with an average of 8 acquisitions) in
      phantom and healthy volunteers. RESULTS: Acquisition time for the 31P-MRS
      procedure with StdP, RS8-4, and RS16-1 in the healthy volunteer studies ranged
      from 30 to 45, 3 to 5, and 3 to 5 minutes, respectively. Metabolite measurements
      of healthy volunteers obtained from 31P-MRS using RS8-4 correlated with values
      obtained using StdP (PCr r2=0.63, P<0.001; ATP r=0.41, P<0.01 and PCr/ATP ratio
      r2=0.25, P<0.05). There was no correlation between StdP and RS16-1 for either ATP
      or the PCr/ATP ratio (r2=0.03, P=0.60, and r2=0.11, p=0.26, respectively).
      Reproducibility (intensity of phosphorus signal) with RS16-1 was worse than that
      of RS8-4 or StdP. CONCLUSION: 31P-MRS using RS8-4 may be a valid diagnostic tool
      for patients with cardiac diseases.

PMID- 15164777
TI  - Magnetic resonance venography in consecutive patients with suspected deep vein
      thrombosis of the upper extremity: initial experience.
AB  - PURPOSE: To assess the feasibility and accuracy of two magnetic resonance (MR)
      venography methods in a consecutive series of patients with suspected deep vein
      thrombosis of the upper extremity (DVTUE). MATERIAL AND METHODS: Consecutive in-
      and outpatients who were referred for imaging of suspected DVTUE in a large
      teaching hospital during the period April 2001 to October 2002 were eligible for
      inclusion. All patients were scheduled to undergo contrast venography with the
      intention to perform additional MR venography. Both time-of-flight and gadolinium
      enhanced 3D MR venography were scheduled. All MR imaging were interpreted
      independently by consensus of two experienced radiologists, who were blinded for
      contrast venography outcome. Patients were managed based on contrast venography
      only. RESULTS: A total of 44 patients were eligible for inclusion. Thirteen
      patients were excluded (5 refused consent, 2 inability to gain venous access, 2
      renal failure, 4 logistic reasons). Contrast venography was performed in 31
      patients, and demonstrated DVTUE in 11 patients. MR imaging was not feasible in
      10 patients (4 unable to lie flat, 3 claustrophobia, 1 too large for MR scanner,
      1 osteosynthesis of shoulder, 1 pacemaker). The sensitivity and specificity of
      TOF MRV versus Gadolinium 3D MRV was 71% and 89% versus 50% and 80%,
      respectively. CONCLUSION: A high number of patients were unable to undergo MR
      venography in this setting. Contrast-enhanced MRV did not improve diagnostic
      accuracy. The clinical utility of MR venography in the setting of suspected DVTUE
      seems disappointing.

PMID- 15164778
TI  - High-resolution computed tomography in healthy smokers and never-smokers: a 6
      year follow-up study of men born in 1933.
AB  - PURPOSE: To elucidate whether emphysematous lesions and other high-resolution
      computed tomography (HRCT) findings considered associated with smoking are part
      of a progressive process, and to measure the extent to which similar changes are
      found in never-smokers. MATERIAL AND METHODS: Healthy smokers and never-smokers
      were recruited from a randomized epidemiological study and investigated with a 6
      year interval. Emphysema, parenchymal and subpleural nodules, ground-glass
      opacities, bronchial alterations, and septal lines were evaluated in 66 subjects
      (40 smokers, 11 of whom had stopped smoking in the interval, and 26 never
      smokers). Lung function was tested. RESULTS: All except emphysematous lesions
      were present to some extent in never-smokers. Emphysema, parenchymal nodules, and
      septal lines occurred significantly more in current smokers, and a progression in
      extent of emphysema, ground-glass opacities, bronchial alterations and septal
      lines was seen. There was no significant change among those who stopped and never
      smokers except for bronchial alterations, which progressed in never-smokers.
      CONCLUSION: In healthy, elderly never-smokers a low extent of various HRCT
      findings has to be considered normal. Emphysema, parenchymal nodules, and ground
      glass opacities are indicative of smoking-induced disease. Further progress may
      cease if smoking is stopped.

PMID- 15164779
TI  - Regional variations in the thickness of cervical spine endplates as measured by
      computed tomography.
AB  - PURPOSE: To determine regional variations in the thickness of human cervical
      spine endplates with high spatial resolution. MATERIAL AND METHODS: Six explanted
      human cadaveric spine specimens underwent computed tomography (CT) scanning.
      Measurement of endplate thickness was done fully automatically at every point of
      the endplate using a computer program written specifically for this purpose.
      Variations in thickness along sagittal and coronal lines were determined and
      statistical parametric mapping was used to test for significant regional
      variations at every point. RESULTS: Anterior and medial aspects of superior
      endplates were shown to be significantly thinner than lateral and dorsal parts.
      Superior endplates were found to be thicker than inferior endplates. CONCLUSION:
      Fully automatic assessment of endplate thickness from CT data is feasible.
      Central regions of the cervical spine endplates are thinner than peripheral parts
      of the endplates. This distribution is more pronounced in superior than in
      inferior endplates.

PMID- 15164780
TI  - Evaluation of bone mineral density of the lumbar spine and proximal femur in
      population-based routine health examinations of healthy Asians.
AB  - PURPOSE: To understand the peak bone mineral density (BMD) and annual loss of BMD
      of the lumbar spine (L-BMD) and the proximal femur (F-BMD) and the prevalence of
      osteoporosis in both sexes in Taipei City, Taiwan. MATERIAL AND METHODS: The
      medical records from a recent 3-year period of annual health examinations at a
      single institution were reviewed. A total of 1514 men (mean age 49.08 +/- 13.62)
      and 1955 women (48.07 +/- 14.12), who lived in the Taipei area, had no major
      systemic disorders, and who had undergone both L-BMD and F-BMD examinations, were
      recruited. RESULTS: In women, peak L-BMD (1.078 +/- 0.133 g/cm2) occurred in the
      30 to 39-year age group, whereas peak F-BMD (0.873 +/- 0.101 g/cm2) occurred in
      the 17 to 29-year age group. In men, peak L-BMD (1.095 +/- 0.137 g/cm2) and F-BMD
      (0.989 +/- 0.140 g/cm2) both occurred in the 17 to 29-year age group. The
      estimated annual bone loss was 0.69% of peak L-BMD in women over 50 years; in the
      proximal femur this was 0.688% in women and 0.332% in men. In women over 60
      years, approximately half of the population had osteoporosis in the lumbar spine.
      CONCLUSION: We report descriptive BMD data of a Chinese population recruited from
      a Taipei urban area who underwent routine health examination. The values are
      similar to or higher than those of Japanese, Canadian and Greek populations. L
      BMD was lower than that in the Lebanese, and F-BMD of both sexes was lower than
      that reported in the Greek study.

PMID- 15164781
TI  - Multidetector computed tomography diagnosis of adult elbow fractures.
AB  - PURPOSE: To assess acute phase multidetector computed tomography (MDCT) findings
      in elbow traumas. MATERIAL AND METHODS: Fifty-six patients (32 M, 24 F, age 16 to
      88 years, mean 44 years) underwent MDCT of the elbow due to an acute trauma
      during a time period of 34 months. RESULTS: A total of 65 fractures and 3 main
      fracture types were established: 16 (25%) ulnar coronoid process fractures, 13
      (20%) radial head fractures, and 12 (18%) humeral supracondylar fractures. Three
      main injury mechanisms were falling (38 (68%) patients), falling from high places
      (6 (11%) patients), and traffic accidents (5 (9%) patients). In 6 (11%) patients,
      MDCT revealed 13 occult fractures in the elbow joint compared to primary
      radiography. In four (7%) patients a displaced fracture fragment was detected in
      primary radiography, but the origin of the fragment was unclear. In all four
      cases, MDCT revealed the origin of the fragment. CONCLUSION: Radiography remains
      the primary imaging modality in elbow trauma, but in complex fracture patterns,
      where the extent of the fractures and the position or origin of dislocated
      fragments is not clear by radiography, the MDCT is a recommended complementary
      examination.

PMID- 15164783
TI  - How quickly does a meningeal cyst increase in size?
AB  - Preoperative imaging of a 45-year-old woman disclosed a large (32 cc) meningeal
      cyst of the thoracic spine. A chest radiograph performed about four and a half
      years earlier exhibited a minute widening of the mediastinum in the same place,
      presumably representing the lesion in its nascent state. It is concluded that a
      meningeal cyst with a linear tendency to grow enlarges by about 6 cc per year.

PMID- 15164782
TI  - Dynamic contrast enhanced magnetic resonance imaging in monitoring bone
      metastases in breast cancer patients receiving bisphosphonates and endocrine
      therapy.
AB  - PURPOSE: To study the role of dynamic contrast enhanced magnetic resonance
      imaging (DCE-MRI) in monitoring the response of bone metastases to endocrine
      therapy combined with bisphosphonates in patients with breast cancer. MATERIAL
      AND METHODS: Ten breast cancer patients with bone metastases who were to receive
      endocrine therapy and bisphosphonates were investigated prospectively by DCE-MRI.
      We chose a reference lesion for each patient who was studied at baseline, within
      3 weeks from the second administration of bisphosphonates, and after 4 and 8
      months from the initiation of medical treatment. Time/intensity curves,
      representing temporal changes of signal intensity in areas of interest in the
      context of the target lesions (ROI), were obtained for each DCE-MRI. RESULTS:
      Changes in the shape of the T/I curves suggesting tumor regression were seen
      shortly after the initiation of medical treatment in the three patients who had
      the most durable responses. CONCLUSION: DCE-MRI has the potential to detect early
      changes related to medical treatment in bone metastases from breast cancer. If
      confirmed in larger series, these data identify DCE-MRI as a diagnostic tool for
      evaluating new bone targeting antineoplastic agents.

PMID- 15164784
TI  - Wallenberg's lateral medullary syndrome: diffusion-weighted imaging findings.
AB  - PURPOSE: To investigate the efficacy of diffusion-weighted imaging in patients
      with Wallenberg's lateral medullary syndrome. MATERIAL AND METHODS: Thirteen
      patients with Wallenberg's lateral medullary syndrome were examined with
      conventional and echoplanar diffusion-weighted magnetic resonance (MR) imaging in
      a 1.5 T magnetic resonance unit. MR examinations were obtained in the acute or
      subacute stage of clinical syndrome, and diffusion-weighted imaging (DWI) was
      considered to be positive for infarction when an increase in signal was seen on b
      = 1000 s/mm2 images in the posterolateral medullary localization. RESULTS: DWIs
      were positive in 12 patients in the acute or subacute stages of this clinical
      syndrome. A false-negative result was obtained in only one patient examined
      within the first day, 10 h after onset of the symptoms. In the visual evaluation
      of the DWI, the contrast between normal and infarcted brainstem area was better
      in the high b-value images than in the apparent diffusion coefficient map images.
      CONCLUSION: DWI is a valuable technique for examining patients presenting with
      the signs and symptoms of Wallenberg's syndrome and high b-value images can
      provide complementary data to T2-weighted images. However, because most of our
      case group were in either the acute or subacute stage, true sensitivity of the
      method in the hyperacute stage of the syndrome remains unclear.

PMID- 15164785
TI  - Report of diffusion-weighted MRI in two cases with different cerebral hydatid
      disease.
AB  - PURPOSE: To present MRI findings in two cases of cerebral hydatid disease with an
      emphasis on diffusion-weighted imaging (DWI) findings of Echinococcus granulosus
      (EG) versus Echinococcus alveolaris (EA). RESULTS: EG lesions were isointense
      with cerebrospinal fluid in all sequences including DWI. On DWI, EA lesions
      remained hypointense on b = 1000 s/mm2 diffusion-weighted images. Apparent
      diffusion coefficient (ADC) values of EG and EA lesions were completely different
      from each other, 2.88 +/- 0.24 x 10(-3) s/mm2 and 1.33 +/- 0.15 x 10(-3) s/mm2,
      respectively. CONCLUSION: The ADC values could not be used to discriminate from
      other differential diagnoses.

PMID- 15164786
TI  - Magnetic resonance imaging findings and outcome in severe tick-borne
      encephalitis. Report of four cases and review of the literature.
AB  - PURPOSE: To describe the magnetic resonance imaging (MRI) findings of four
      patients with proven tick-borne encephalitis (TBE). These are the most northern
      cases reported from Scandinavia. Experience of turbo fluid-attenuated inversion
      recovery (FLAIR) and diffusion-weighted imaging (DWI) has not previously been
      published in this context. MATERIAL AND METHODS: The MRI findings of four
      consecutive patients with TBE treated in our hospital during the year 2002 were
      evaluated. MRI was done during the first week of illness, and follow-up scans
      were available in three cases. RESULTS: In T2-weighted and turbo FLAIR images,
      thalamic hyperintensity was equally evident in three of the four patients. One of
      them also showed hyperintensity in the left putamen and the internal capsule and
      another patient in the peduncles and the hypothalamus. T1-weighted images without
      contrast were normal in all patients, and leptomeningeal enhancement was detected
      in only one patient. The two patients who underwent DW images did not show any
      restricted diffusion. Follow-up MR images showed no atrophy or necrotic foci, and
      the signal abnormalities disappeared during 16-34 weeks of follow-up. CONCLUSION:
      T2-weighted and turbo FLAIR sequences proved equally effective in detecting and
      delineating the thalamic, brainstem, and basal ganglia pathologies. According to
      our results, mechanisms other than cytotoxic edema contribute to the signal
      pathology. Radiologists should be familiar with the MR findings of TBE even in
      non-endemic areas.

PMID- 15164787
TI  - Multi-slice computed tomography urography after diuretic injection in children
      with urinary tract dilatation.
AB  - PURPOSE: To evaluate the potential use of multi-slice computed tomography
      urography (MSCTU) after diuretic injection in children with urinary tract
      dilatation. MATERIAL AND METHODS: MSCTU was performed in 19 patients (11 boys, 8
      girls, mean age 5.4 years) with suspicion of urinary tract obstruction and
      dilatation. Furosemide, 1 mg/kg, was injected 3 min before contrast material
      administration and followed by a bolus of 30 ml of physiologic saline solution
      immediately after application of contrast material. Excretory-phase images were
      obtained through the abdomen and pelvis beginning 10 min after initiation of the
      injection of contrast material. Maximum intensity projection (MIP) and volume
      rendering (VR) images were post-processed to obtain urographic views. RESULTS:
      MSCTU revealed pathology in 16 of 19 patients, while 3 patients had normal
      findings. Ureteropelvic obstruction was found in 4 patients, obstructive
      megaureter in 8. Both ureteropelvic obstruction and obstructive megaureter were
      disclosed in 1 patient, partial ureteral duplication in 1 patient, and both
      complete ureteral duplication and ureterocele in 2 patients. In all patients, MIP
      and VR images could satisfactorily show the pathologies of the urinary tract. The
      estimated effective average doses of MSCTU were higher than IVU. CONCLUSION:
      Preliminary results of furosemide-enhanced MSCTU demonstrated consistently
      dilated urinary tracts, obstruction levels, and underlying pathologies better
      than US and IVU.

PMID- 15164788
TI  - Pelvic imaging: multicystic uterine cervical lesions. Can magnetic resonance
      imaging differentiate benignancy from malignancy?
AB  - PURPOSE: To evaluate whether magnetic resonance imaging (MRI) can be used to
      differentiate between malignant and benign multicystic uterine cervical lesions.
      MATERIAL AND METHODS: Twenty-two patients with cervical adenocarcinomas,
      including minimal deviation adenocarcinoma, and five patients with benign
      multicystic lesions were classified as a percentage of solid components on MRI.
      Cystic components were further classified by average cyst diameter and signal
      intensity of the cyst fluid on T1WI. RESULTS: All nine of the entirely solid
      lesions were malignant. In contrast, two of the entirely cystic lesions were
      benign. Ten of the ordinary adenocarcinomas had both solid and cystic components.
      However, three of the 16 solid and cystic lesions were benign. Lesions composed
      of cysts smaller than 5mm tended to be malignant; however, some lesions composed
      of larger cysts were also malignant. Three of 5 lesions with low-signal and 7 of
      10 with intermediate-signal fluid were malignant. CONCLUSION: The malignancy
      potential was higher in the lesions with a higher percentage of solid components.
      However, determining whether multicystic lesions were benign or malignant based
      on the existence of solid components, the average cyst size, and the signal
      intensity of cyst fluid was impossible. Although a multicystic lesion with solid
      components in the deep cervical stroma had been reported as a MR finding of a
      minimal deviation adenocarcinoma, this does not appear to be pathognomonic.

PMID- 15164789
TI  - Double accessory fissures in the upper lobe of the right lung (double azygos
      fissures?): high resolution computed tomography appearance.

PMID- 15164790
TI  - Spontaneous rupture of mediastinal cystic teratoma with high levels of amylase,
      lipase, CA 19-9, CA 125 and CEA in cystic fluid: a case report.

PMID- 15164791
TI  - Influence of DNA double-strand break rejoining on clonogenic survival and
      micronucleus yield in human cell lines.
AB  - PURPOSE: To examine the role of DNA double-strand break (DSB) rejoining in cell
      survival and micronucleus yield after 60Co gamma-irradiation. MATERIALS AND
      METHOD: Thirteen human cell lines (six glioblastoma, five prostate, one melanoma,
      one squamous cell carcinoma) were irradiated with 60Co gamma-rays to doses of 0
      10Gy for cell survival and micronucleus measurements and 0-100Gy for DSB
      rejoining. Measurements were performed using standard clonogenic, micronucleus
      and constant-field gel electrophoresis assays. RESULTS: Radioresistance and
      micronucleus yield were positively correlated (r=0.74, p=0.004). A significant
      cell type-dependent correlation was demonstrated between total (0-20 h) DSB
      rejoining and cell survival (r=0.86, p=0.03 for glioblastomas; r=0.79, p=0.04 for
      other cell lines), with more resistant cell lines showing higher levels of DSB
      rejoining. No relationship was apparent between fast (0-2 h) or slow (2-20 h) DSB
      rejoining and clonogenic survival. While there was no relationship between total
      or slow DSB rejoining and micronucleus yield, a significant and cell type
      specific correlation emerged between fast rejoining and micronucleus yield for
      the glioblastomas (r=0.89, p=0.04) and other cell lines (r=0.76, p=0.04). Cell
      lines with higher levels of DSB rejoining within 2 h of irradiation showed higher
      yields of micronuclei. CONCLUSION: Fast DSB rejoining, possibly through
      interaction with slow DSB rejoining, appears to play an important role in the
      formation of micronuclei. However, total DSB rejoining reflects intrinsic
      radiosensitivity. Consideration of differences in DSB rejoining kinetics might
      contribute to a better understanding of the significance of cell survival and
      micronucleus data in the clinical and radiation protection setting.

PMID- 15164792
TI  - Induction and detection of bystander effects after combined treatment of cells
      with 5-bromo-2'-deoxyurine, Hoechst 33 258 and ultraviolet A light.
AB  - PURPOSE: A combined treatment of cells with 5-bromo-2'-deoxyurine (BrdU), Hoechst
      33 258 and ultraviolet A (UVA) light was used to introduce chromosomal
      aberrations in cells for the study of bystander effects in non-labelled cells.
      MATERIALS AND METHODS: Mixtures of BrdU-labelled and non-labelled Chinese hamster
      cells (V79) in S phase were exposed to Hoechst 33 258 and/or UVA light. Metaphase
      cells were collected and analysed for chromosomal aberrations by Giemsa staining.
      BrdU immunostaining was performed to verify BrdU incorporation in the cells.
      RESULTS: Combined treatment with BrdU, Hoechst dye and UVA light induced reduced
      cell survival and increased chromosomal aberrations, whereas treatment with
      Hoechst 33 258 and/or UVA light had no effect on cells. Elevated frequencies of
      chromosomal aberrations were found in non-labelled cells mixed with BrdU-labelled
      cells and exposed to Hoechst dye and UVA light, suggesting the induction of
      bystander effects by damaged BrdU-labelled cells. These bystander clastogenic
      effects were also observed in non-labelled cells mixed with dying cells,
      indicating a contribution of dying cells in the induction of the bystander
      effects. CONCLUSIONS: The combined treatment with BrdU, Hoechst 33 258 and UVA
      light is a valid method for the study of bystander effects as it enables both
      induction of DNA damage and discrimination of targeted cells and bystander cells.

PMID- 15164793
TI  - Dose-dependent biphasic induction and transcriptional activity of nuclear factor
      kappa B (NF-kappaB) in EA.hy.926 endothelial cells after low-dose X-irradiation.
AB  - PURPOSE: Low-dose radiotherapy is known to exert an anti-inflammatory effect, but
      the underlying radiobiological mechanisms are still elusive. It was recently
      reported that transforming growth factor (TGF) beta1 essentially contributes to
      the reduced adhesion of peripheral blood mononuclear cells to endothelial cells
      at low-dose X-irradiation. As the transcription factor nuclear factor kappa B (NF
      kappaB) is crucially involved in mediating an inflammatory response by inducing
      the expression of cytokines and adhesion molecules, NF-kappaB DNA binding and
      transcriptional activity as well as its impact on the expression of TGF-beta1 in
      EA.hy.926 endothelial cells were analysed subsequently to low-dose radiotherapy.
      MATERIALS AND METHODS: Human EA.hy.926 endothelial cells were grown to
      subconfluence. Twenty hours after X-irradiation with single doses ranging from
      0.3 to 3 Gy, the cells were activated with tumour necrosis factor-alpha. Four
      hours later, the cells were harvested. NF-kappaB DNA-binding activity of nuclear
      extracts was analysed by electrophoretic mobility shift assay. The NF-kappaB
      subunits p50, p65/RelA, c-Rel and RelB of the NF-kappaB complexes were quantified
      by enzyme-linked immunoabsorbant assay. The transcriptional activity of NF-kappaB
      was measured using luciferase reporter gene assays in EA.hy.926 endothelial cells
      transiently transfected with the plasmid pB2xLuc. To correlate transcriptional
      activity to TGF-beta1 expression, NF-kappaB decoy oligonucleotides were used to
      inhibit NF-kappaB activity and TGF-beta1 secretion. RESULTS: After low-dose
      radiotherapy, an increased NF-kappaB DNA-binding activity was observed in
      stimulated EA.hy.926 endothelial cells with a relative maximum (threefold
      induction) at 0.5 Gy. The NF-kappaB activation then decreased after X-irradiation
      at 0.6-0.8 Gy and subsequently increased again at doses of 1 and 3 Gy. This
      biphasic induction profile of NF-kappaB was confirmed by the analysis of the NF
      kappaB-specific transcriptional activity. The latter showed a relative maximum at
      0.5 Gy, a relative minimum between 0.5 and 1.0 Gy, and an increase at 3 Gy.
      Transfection of EA.hy.926 endothelial cells with NF-kappaB decoy oligonucleotides
      before irradiation resulted in a 50% reduction of TGF-beta1 secretion at 0.5 Gy
      compared with control oligonucleotides or untreated cells. CONCLUSIONS: Low-dose
      radiotherapy induces a biphasic activation of NF-kappaB with a relative maximum
      at 0.5 Gy. The induction by NF-kappaB of TGF-beta1 in endothelial cells might
      contribute to the anti-inflammatory properties of low-dose ionizing irradiation.

PMID- 15164794
TI  - Role of DNA-dependent protein kinase in the process of radiation-induced
      aberration formation.
AB  - PURPOSE: To further investigate the role of DNA-dependent protein kinase (DNA-PK)
      and ataxia-telangiectasia mutation (ATM) in the formation of chromosome
      aberrations, we analysed radiation-induced aberrations in M059J cells,
      complemented with the PRKDC (DNA-PK) gene by introducing a fragment of human
      chromosome 8 containing a copy of the human PRKDC gene. One hybrid cell line
      (M059J Fus1) displayed kinase activity and was radioresistant; the other hybrid
      cell line (M059J Fus9) showed no kinase activity and was radiosensitive. Both
      Fus1 and Fus9 cells have only a low ATM activity. Wortmannin, an inhibitor of DNA
      PKCS and ATM, was added before irradiation in order to study the effect of DNA
      PKCS--and ATM--inhibition on the formation of chromosome aberrations.
      Furthermore, aberration formation was studied in a lymphoblastoid ATM-deficient
      cell line AT-1 and in an ATM-proficient control. MATERIALS AND METHODS: Confluent
      cells were irradiated with 200 kV X-rays. Dicentrics, excess acentric fragments,
      chromatid/ isochromatid breaks and chromatid exchanges were scored in the absence
      and presence of wortmannin. RESULTS: In M059J-Fus1 cells and normal
      lymphoblastoid cells, only chromosome-type aberrations were observed
      independently of the presence of wortmannin. In DNA-PK-deficient Fus9 cells and
      in ATM-deficient AT-1 cells, an increasing proportion (30-80%) of cells
      containing chromatid-type aberrations was observed. This proportion increased
      with irradiation dose and with wortmannin addition. The aberration yields
      observed in the complemented M059J-Fus1 cell line were much lower than the
      corresponding yields observed in the deficient M059J and AT-1 cell lines.
      However, the low yields observed in the DNA-PK-proficient 'wild-type' cell line
      M059K were not completely restored. CONCLUSIONS: Since in M059J-Fus1 cells the
      radioresistant phenotype with respect to chromosome-type aberration formation was
      restored by the complementation of PRKDC, ATM expression determines the
      chromosomal radiosensitivity of M059J cells only to a minor extent. The
      increasing presence of chromatid-type aberrations in cells irradiated in G0/G1
      phase as observed either in DNA-PK- or ATM-deficient cells definitely requires
      the lack of either kinase. Thus, the aberration spectrum observed is determined
      by the genetic profile of the respective cells and aberration class amplitudes
      can be modulated by the inhibition of either kinase.

PMID- 15164795
TI  - Chromosome aberrations and cell inactivation induced in mammalian cells by
      ultrasoft X-rays: correlation with the core ionizations in DNA.
AB  - PURPOSE: To study the frequency of chromosome aberrations induced by soft X-rays.
      To see if the core ionization of DNA atoms is involved in this end-point as much
      as it appears to be in cell killing. MATERIALS AND METHODS: V79 hamster cells
      were irradiated by synchrotron radiation photons iso-attenuated in the cell (250,
      350, 810eV). The morphological chromosome aberrations detected in the first post
      irradiation cell division (dicentrics and centric rings) were studied by Giemsa
      staining. RESULTS: The chromosome aberrations at 350eV were, respectively, 2.6 +/
      0.8 and 2.1 +/- 0.8 times more numerous than at 250 and 810eV for the same
      average dose absorbed by the nucleus. These relative effectivenesses are
      comparable with the ones already measured for cell killing. Moreover, they
      roughly vary such as the relative numbers of core ionizations (including in the
      phosphorus L-shell) produced in DNA and its bound water (water being involved
      only at 810eV through the oxygen atoms). In particular, they reproduce the
      characteristic twofold enhancement at 350eV, above the carbon K threshold.
      CONCLUSIONS: Correlations suggest that the core ionization process is likely a
      common and essential mechanism initiating both chromosome aberration and cell
      killing end-points at these photon energies.

PMID- 15164797
TI  - Effect of americium-241 alpha-particles on the dose-response of chromosome
      aberrations in human lymphocytes analysed by fluorescence in situ hybridization.
AB  - PURPOSE: To evaluate by the fluorescent in-situ hybridization (FISH) technique
      the dose-response and intercellular distribution of alpha-particle-induced
      chromosome aberrations. In particular, the validity of using the yield of
      characteristic types of chromosome abnormalities in stable cells as quantitative
      indicators for retrospective dose reconstruction has been evaluated. MATERIAL AND
      METHODS: Monolayers of human peripheral lymphocytes were exposed at doses from
      0.02 to 1 Gy to alpha-particles emitted from a source of americium-241. The most
      probable energy of the alpha-particles entering the cells was 2.7 MeV. FISH
      painting was performed using DNA probes for chromosomes 2, 4 and 8 in combination
      with a pan-centromeric probe. In complete first-division cells, identified by
      harlequin staining, aberrations involving painted target chromosomal material
      were recorded as well as aberrations involving only unpainted chromosomal
      material. RESULTS: In total, the percentage of complex aberrations was about 35%
      and no dose dependence was observed. When complex-type exchanges were reduced to
      simple base types, the different cell distributions were clearly over-dispersed,
      and the linear coefficients of the dose-effect curves for translocations were
      significantly higher than for dicentrics. For past dose reconstruction, only a
      few complex aberrations were in stable cells. The linear coefficient obtained for
      transmissible aberrations in stable cells was more than seven times lower than
      that obtained in all analysed cells, i.e. including unstable cells. CONCLUSION:
      FISH-based analysis of complex rearrangements allows discrimination between
      partial-body exposures to low-linear energy transfer radiation and high-linear
      energy transfer exposures. In assessing past or chronic exposure to alpha
      particles, the use of a dose-effect curve obtained by FISH-based translocation
      data, which had not excluded data determined in unstable cells, would
      underestimate the dose. Insertions are ineffective biomarkers because their
      frequency is too low.

PMID- 15164796
TI  - Chromosomal aberrations in uranium and coal miners.
AB  - PURPOSE: To compare chromosomal aberrations in peripheral lymphocytes of Wismut
      uranium miners (WUM) and Ruhr coal miners (RCM). MATERIALS AND METHODS:
      Peripheral lymphocytes from 66 WUM and 29 RCM were cultured and analysed for
      structural chromosomal aberrations in Giemsa-stained M1 metaphases. Cytogenetic
      data from 23 male white-collar workers from public services were used as a
      historical control group. RESULTS: The frequencies of chromosomal aberrations and
      sister chromatid exchanges in WUM and RCM were quite similar. Compared with
      public services workers, WUM and RCM had significantly higher frequencies of
      chromosomal aberrations. CONCLUSIONS: Chromosomal aberrations in WUM are not
      induced by radioactive particles inhaled during underground mining but as in RCM
      rather result from factors such as age, lifestyle, illnesses, medications and
      diagnostic irradiations.

PMID- 15164798
TI  - Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium.
AB  - PURPOSE: To test the hypothesis that non-lethal hypotonia will enhance ultrasound
      induced cell killing in vitro and that the mechanism is mechanical in nature.
      MATERIALS AND METHODS: Hypotonic RPMI medium (146 mOsm) was used to induce non
      lethal osmotic swelling of human myelomonocytic leukaemia U937 cells. Hypotonia
      for 10 min was started just before exposure to 1 MHz ultrasound at 0.5 or 1.0
      Wcm(-2) for 10 min, or 5 min before exposure to 2.0 Wcm(-2) for 1 min. Surviving
      intact cells were then determined by the trypan blue dye exclusion test
      immediately after treatment. After 6-h incubation of the treated cells, early
      apoptosis and secondary necrosis were measured using a flow cytometer.
      Intracellular free calcium ion imaging by Fura-2 fluorescence and cellular ion
      scanning using a secondary ion mass spectrometer were also performed. RESULTS:
      Enhancement of ultrasound-induced cell lysis was observed at all intensities, and
      most prominently at 2.0 Wcm(-2), while apoptosis induction was significantly
      enhanced at intensities of 0.5 and 1.0 Wcm(-2), but not at 2.0 Wcm(-2). The
      enhanced cell lysis is attributed to the increased susceptibility of the cells to
      mechanical damage. This is consistent with previous reports describing the
      effects of mechanical stresses on cell membranes. Cellular ion scanning images
      also suggest that hypotonia has an effect on the membrane damage-and-repair
      mechanism of the cells. CONCLUSIONS: The results support the hypothesis that non
      lethal hypotonia can enhance ultrasound-induced cell killing. These findings also
      suggest the 'sonomechanical' nature of the effects on the cells.

PMID- 15164799
TI  - Modification of radiation-induced acute oral mucositis in the rat.
AB  - PURPOSE: A new non-toxic drug (compound A) consisting of curcumin, alpha
      tocopherol and sunflower oil was developed and its efficacy tested in the
      treatment of radiation-induced oral mucositis in the rat. MATERIAL AND METHODS:
      Mature (12 weeks old, 200-225 g) female Sprague-Dawley rats were used. While
      under general anaesthesia, the tongues of the animals were slightly extended
      outside and a region of the underside of the tongue was irradiated in-situ with
      single doses of 2.27 MeV beta-rays from a 5-mm diameter 90Sr/90Y plaque. The dose
      rate of the source was about 10 Gy min(-1) at the surface of the mucus membrane.
      Irradiations and subsequent assessment of the lesion were carried out under
      general anaesthesia maintained by a 1.5% halothane/oxygen mixture. Six groups of
      animals were irradiated with single doses of 13.5, 15.0, 16.5 or 18Gy. One
      subgroup (radiation only) received no further treatment, while the other five
      groups received 0.5 ml day(-1) of either compound A, sunflower oil, alpha
      tocopherol, curcumin or water containing 10% ethanol by oral gavage until the end
      of experiments. Mucosal ulceration (erosion of mucosal epithelium) was considered
      as an end-point. From the day after irradiation until any acute radiation-induced
      oral mucosal lesion had healed, the tongues of the animals were assessed daily
      for the presence of radiation-induced mucositis (mucosal ulceration). Quantal
      data for the incidence of radiation-induced mucositis were analysed using logit
      analysis and a dose-modification factor was obtained. RESULTS: There was a modest
      increase in ED50, the dose expected to cause mucositis in 50% of the animals
      after both alpha-tocopherol and sunflower oil were administered. This resulted in
      dose-modification factors of 1.05. While curcumin treatment resulted in a dose
      modification factor of 1.09. Compound A significantly reduced the incidence of
      radiation-induced mucositis with a statistically significant dose-modification
      factor of 1.2 +/- 0.1. CONCLUSIONS: Curcumin and other components of compound A
      appeared to be effective in the prevention of radiation-induced oral mucositis.
      However, the overall effect observed with the combination drug (compound A)
      appeared greater than additive.

PMID- 15164800
TI  - ISPOR's "Code of Ethics for Researchers": is it ethical?

PMID- 15164801
TI  - ISPOR Code of Ethics for Researchers background article--report of the ISPOR Task
      Force on Code of Ethics for Researchers.
AB  - In 2001, ISPOR convened a Task Force on Code of Ethics for Researchers (The Task
      Force). This Task Force was to build on the previous work of ISPOR Health Science
      Policy Task Forces and develop a code of ethics that would be applicable to all
      ISPOR members and to ISPOR itself. The Task Force developed a code of ethics that
      was subsequently adopted by the ISPOR Board of Directors. The Code of Ethics is
      appended to this article and can be found on ISPOR's Web page at
      http://www.ispor.org/workpaper/code_ethic.htm. This article provides supportive
      information and justification for the ISPOR Code of Ethics for Researchers and
      includes a discussion of the stakeholders as well as ethical considerations for
      the researcher on research practices, research sponsorship, research publication
      and dissemination, and relationships with others. It also includes a discussion
      of the ethical considerations for the Society.

PMID- 15164802
TI  - What is next for pharmacoeconomics and outcomes research in Asia?
AB  - OBJECTIVES: Pharmacoeconomics and outcomes research have the potential for rapid
      adoption in the Asia Pacific region. Nevertheless, the region is characterized by
      great diversity in social and economic development, ethnicity, population size,
      health-care system, culture, language, and religion. Thus, the rate of adoption
      is also quite diverse across the region. METHODS: Among the countries reviewed in
      this article, governments take varying levels of interest in applying this
      research in health policy decisions. For example, some countries have already
      implemented systems that require pharmacoeconomic studies as one component of a
      new pharmaceutical product's approval for reimbursement, whereas others recommend
      such data but do not require it in policy and medical decision making. The
      literature in the countries reviewed is actually quite robust given the early
      stages of development of this field in most countries. The academic community has
      members trained in this field of research in all the countries reviewed and some
      universities have established departments whereas others have just introduced a
      few classes in the area. RESULTS: At the moment, pharmacoeconomics and outcomes
      research are being conducted mainly by academics. In addition, some
      pharmaceutical researchers are active and pharmaceutical companies are currently
      preparing to conduct more of this research as part of their strategy for Asian
      drug development. CONCLUSIONS: Prospects for future growth and development in
      this field are quite good in Asia as rapid healthcare inflation, increasing rates
      of chronic conditions and aging population, and increasing technology diffusion
      will underpin the need for greater awareness of the need to incorporate economic
      efficiency into the health-care systems.

PMID- 15164803
TI  - Seniors with chronic health conditions and prescription drugs: benefits, wealth,
      and health.
AB  - OBJECTIVES: The objectives of this study were to examine the relationship between
      prescription benefit status and access to medications among Medicare
      beneficiaries with hypertension, congestive heart failure, coronary artery
      disease, and diabetes and to determine how income, wealth, and health status
      influence this relationship. METHODS: We analyzed survey and administrative data
      for 4492 Medicare + Choice enrollees aged 67 and above enrolled in a
      predominantly group-model health maintenance organization in 2000. Outcome
      measures included difficulty affording medications, methods of coping with
      medication costs including obtaining medicines from another country, using free
      samples, and stretching out medications to make them last longer. Independent
      variables included prescription benefit status, income, wealth measures, health
      status, and out-of-pocket prescription drug spending. RESULTS: Lacking a
      prescription benefit was independently associated with difficulty affording
      medications (25% of those without a benefit vs. 17% with a benefit) and coping
      methods such as stretching out medications. Lower income, lower assets, and worse
      health status also independently predicted greater difficulty as measured by
      these outcomes; there was no effect modification between these factors and
      benefit status. Relative to national figures, out-of-pocket spending in this
      setting was quite low, with only 0.2 and 13% of those with and without a benefit,
      respectively, spending over 100 dollars per month. Higher out-of-pocket spending
      predicted greater difficulty affording medications but not stretching out
      medications. CONCLUSIONS: Efforts to improve medication accessibility for older
      Americans with chronic conditions need to address not only insurance coverage but
      also barriers related to socioeconomic status and health status.

PMID- 15164804
TI  - Resource utilization and costs of stroke unit care in Germany.
AB  - OBJECTIVES: Stroke imposes a considerable economic burden on the individual and
      society. Recently, the concept of an integrated stroke unit has been established
      in several countries to improve the outcome of patients. This study evaluates the
      costs of acute care of the different cerebrovascular insults in a stroke unit.
      METHODS: The study population included 340 patients who were consecutively
      admitted to the Department of Neurology, Philipps University Marburg, with the
      diagnosis of stroke or transient ischemic attack (TIA) between January 1 and June
      30, 2000. Clinical status and course were evaluated by using the Barthel index
      and the modified Rankin scale. Employing a "bottom-up" approach, we calculated
      the costs from the perspective of the hospital and the third-party payer using
      data from provider departments and other published sources. RESULTS: Inpatient
      costs were 3020 euros (3290 US dollars) for TIA, 3480 euros (3790 US dollars) for
      ischemic stroke (IS), and 5080 euros (5540 US dollars) for intracerebral
      hemorrhage (ICH) and differed significantly among these subgroups (P < .05).
      Patient subgroups ranked in the same order for average length of stay at 9.4 days
      for TIA, 10.2 days for IS, and 11.9 days for ICH (P > .05). Approximately 30% of
      the hospital costs are due to physician charges and care. Imaging amounted to 10%
      and lab investigations to 14% of total costs, independent of the diagnosis.
      Postacute treatment, including inpatient rehabilitation, cost 9880 euros per
      patient. Across all diagnostic groups, a mean clinical improvement was observed
      at time of discharge. CONCLUSIONS: Care of patients with cerebrovascular events
      in a stroke unit causes a high demand of resources and has a considerable impact
      on health-care expenditure. Therefore, investigations comparing the stroke unit
      concept with other strategies in stroke care are necessary to evaluate the stroke
      unit concept for a rational use of available resources in patients with
      cerebrovascular events.

PMID- 15164805
TI  - A computer simulation model of the natural history and economic impact of chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health problem
      with high societal costs. The Global Initiative for Chronic Lung Disease (GOLD)
      has identified a need for health economics data for COPD. For chronic diseases,
      such as COPD, where the natural history of disease is lifetime, a modeling
      approach for economic evaluation may be more realistic than prospective, piggy
      backed clinical trials or specific COPD cohort studies. Simulation models can be
      used to extrapolate clinical data beyond the limited time frame of clinical
      trials, to analyze subgroups of patients or to explore uncertainty regarding the
      results by using sensitivity analysis techniques. Our purpose has been to develop
      a flexible computer simulation model for COPD that will represent disease
      progression and GOLD recommendations, useful for economic evaluations of new
      medicines to meet the needs of various payer requirements for reimbursement and
      resource allocation. METHODS: This article describes a two-dimensional Markov
      model, which uses data from multiple sources about disease progression,
      exacerbation frequency and duration, mortality, costs, burden of illness, and the
      relationships between those variables. The model is evaluated using stochastic
      uncertainty analysis, it allows comparison of treatments affecting different
      disease mechanisms, and it uses primary data validated against published sources.
      RESULTS: We have evaluated two hypothetical interventions treating different
      features of the disease (lung function decline and acute exacerbations). These
      analyses show that reducing lung function decline must be a long-term strategy
      compared to reducing the number of exacerbations. It was necessary to have a long
      term like 30 years, with 10,000 patients and 20% increase in price, or 20 years
      with equal prices to show cost-effectiveness with statistical significance for a
      treatment that reduces lung function decline. CONCLUSIONS: Our study shows the
      value of modeling as a tool for evaluating different scenarios and for combining
      several sources of data, to provide estimates that would otherwise be
      unavailable. Clinical trials of this size and duration would be unrealistic.

PMID- 15164806
TI  - The SCOPE study: health-care consumption related to patients with chronic
      obstructive pulmonary disease in France.
AB  - OBJECTIVE: The main objective of the SCOPE study was to estimate the total direct
      medical costs of patients with treated chronic obstructive pulmonary disease
      (COPD) in France according to severity stages. METHODS: Total medical resources
      consumption of a sample of COPD patients was collected over a 12-month period
      through a national physician survey (including both general practitioners and
      lung specialists). This survey was completed for 255 patients. Data were then
      extrapolated to all patients with diagnosed and treated COPD in France. Average
      total medical resources consumption of a COPD patient per year was 4366 euros.
      Among this cost 41% was directly related to COPD follow-up, 25% to COPD-related
      complications (mainly exacerbations), and 34% to other diseases. More than one
      third of the total direct COPD cost was related to hospitalizations and 31% to
      drug consumption. COPD-related costs increased markedly with severity based on
      FEV1 (but data suggested the existence of a threshold effect). SCOPE data did not
      show any evidence of a significant relationship between direct medical cost and
      patient age, sex, addiction to tobacco, or duration of COPD. The total medical
      consumption of COPD patients in France was 3.5 billion euros and accounted for
      3.5% of the total medical expenditures (prevalence of COPD was estimated 1.3% in
      the general population). RESULTS: The SCOPE study revealed the high level of
      medical resources consumption of patients with COPD. CONCLUSIONS: The burden of
      COPD itself and its complications appeared to be of considerable magnitude in
      France especially for severe COPD.

PMID- 15164807
TI  - Cost-effectiveness analysis of interventions to enhance mammography compliance
      using computer modeling (CAN*TROL).
AB  - OBJECTIVE: Tailored telephone counseling and physician-based and clinic-based
      interventions have been shown to be cost-effective in enhancing utilization of
      mammography among nonadherent women. The objective of this study was to evaluate
      the costs and benefits of a broad implementation of these interventions from a
      health payer perspective. METHODS: CAN*TROL computer modeling was employed in the
      cost-effectiveness analysis of interventions in a 2000 Texas female population.
      The estimated effects of the various interventions and their related costs
      derived from the literature were applied to a hypothetical scenario of a broad
      implementation of these interventions. RESULTS: Seven studies were identified
      from the literature, six of them employed tailored telephone counseling (TC),
      whereas two used comprehensive physician-based (PB) or clinic-based (CB)
      interventions. The estimated intervention cost per women was 43 dollars for TC,
      71 dollars for PB, and 151 dollars for CB. CAN*TROL model showed that after 15
      years of implementation, TC, PB, and CB could reduce cancer mortality by 6.5,
      2.2, and 10.7%, respectively. The cumulative net costs of interventions,
      mammography screening, and medical care costs were lower for TC (TC vs. PB vs.
      CB, 1.05 million vs. 1.06 million vs. 1.60 million). Nevertheless, CB resulted in
      more life-years saved (TC vs. PB vs. CB, 11,413 vs. 8515 vs. 14,559). The
      incremental cost-effectiveness ratio was more favorable for tailored telephone
      counseling interventions. One-way sensitivity analysis indicated that compliance
      rates and intervention costs had the most significant impact on the incremental
      cost-effectiveness ratio. CONCLUSION: Tailored telephone counseling interventions
      may be the preferred first-line intervention for getting nonadherent women aged
      50 to 79 years on schedule for mammography screening.

PMID- 15164808
TI  - Out-of-pocket health-care expenditures among older Americans with cancer.
AB  - OBJECTIVE: There is currently limited information regarding the out-of-pocket
      expenditures (OOPE) for medical care made by elderly individuals with cancer. We
      sought to quantify OOPE for community-dwelling individuals age 70 or older with:
      1) no cancer (No CA), 2) a history of cancer, not undergoing current treatment
      (CA/No Tx), and 3) a history of cancer, undergoing current treatment (CA/Tx).
      METHODS: We used data from the 1995 Asset and Health Dynamics Study, a nationally
      representative survey of community-dwelling elderly individuals. Respondents
      identified their cancer status and reported OOPE for the prior 2 years for: 1)
      hospital and nursing home stays, 2) outpatient services, 3) home care, and 4)
      prescription medications. Using a multivariable two-part regression model to
      control for differences in sociodemographics, living situation, functional
      limitations, comorbid chronic conditions, and insurance coverage, the additional
      cancer-related OOPE were estimated. RESULTS: Of the 6370 respondents, 5382 (84%)
      reported No CA, 812 (13%) reported CA/No Tx, and 176 (3%) reported CA/Tx. The
      adjusted mean annual OOPE for the No CA, CA/No Tx, and CA/Tx groups were 1210
      dollars, 1450 dollars, and 1880 dollars, respectively (P < .01). Prescription
      medications (1120 dollars per year) and home care services (250 dollars)
      accounted for most of the additional OOPE associated with cancer treatment. Low
      income individuals undergoing cancer treatment spent about 27% of their yearly
      income on OOPE compared to only 5% of yearly income for high-income individuals
      with no cancer history (P < .01). CONCLUSIONS: Cancer treatment in older
      individuals results in significant OOPE, mainly for prescription medications and
      home care services. Economic evaluations and public policies aimed at cancer
      prevention and treatment should take note of the significant OOPE made by older
      Americans with cancer.

PMID- 15164809
TI  - The impact of managed eye care on use of vision services, vision costs, and
      patient satisfaction.
AB  - OBJECTIVES: This study was designed to evaluate the impact of introducing a
      managed vision benefit program on the use and costs of vision services in a
      managed care setting and also to assess satisfaction with those services after
      the program was introduced. METHODS: Utilization and costs were compared for two
      groups of patients. The comparison group (n = 36,168) included all patients
      enrolled for 18 months before implementation of the managed eye-care plan. The
      study group (n = 23,816) included those enrolled for 18 months following its
      implementation. Medical claims, survey, and administrative data were used to
      evaluate study outcomes. RESULTS: The overall use of vision care was similar
      before and after the introduction of the managed eye-care programs, with 24% of
      each group receiving at least one vision service during the 18-month period.
      Nevertheless, an increase in the use of routine eye-care services and a decrease
      in medical eye-care services were observed following program implementation. The
      overall cost of providing eye-care services to patients decreased from 1.86
      dollars to 1.36 dollars per member per month after the program started, largely
      owing to a reduction in spending associated with medical eye-care services. More
      than 90% of patients surveyed were satisfied with their vision care provided by
      the program. CONCLUSIONS: Findings suggest that introducing routine and medical
      managed eye-care programs in a managed care setting allows for a reduction in
      medical costs while maintaining access to care and patient satisfaction.

PMID- 15164811
TI  - Inconsistency in DTCA practices by manufacturers: is it time to standardize print
      summaries?

PMID- 15164810
TI  - Satisfaction with medication: an overview of conceptual, methodologic, and
      regulatory issues.
AB  - OBJECTIVE: Patients' satisfaction with their medication or medical device has
      been of increasing interest over the past decade. This is reflective of the rise
      of the patient as consumer and the desire of pharmaceutical and device
      manufacturers to obtain feedback from the consumers about their products.
      Satisfaction with medication is more narrowly focused and should be distinguished
      from other aspects of satisfaction. The purpose of this article is to place the
      concept of patient satisfaction with medication in an appropriate theoretical
      context, to explore the challenges of performing this research, and to offer
      recommendations for the basis of satisfaction claims. METHODS: We reviewed the
      literature on satisfaction with medication or medical devices. We summarize and
      discuss the background, conceptual issues, and theoretical justification for
      studying satisfaction with medication. We offer examples of domains to be
      included and suggestions on how to develop a psychometrically sound satisfaction
      measure. We also address additional issues for consideration. RESULTS: Medication
      satisfaction is a type of patient-reported outcome, but is distinguished from
      other patient-reported outcomes-specifically health-related quality of life
      (HRQL) and self-reports of symptoms. The Theory of Reasoned Action provides one
      theoretical justification for the concept. The heuristic value of this theory
      leads to implications regarding the relation between satisfaction and adherence.
      In addition, the theory is consistent with the need to focus on the patient's
      beliefs and values concerning the impact of taking his/her medication. Although
      the beliefs will differ according to the specific drug-disease combination, the
      beliefs can often be categorized in several domains of satisfaction: symptom
      relief/efficacy, side effects, ease and convenience, impact on HRQL, general
      satisfaction, and additional domains specific to the given research question.
      CONCLUSION: Patient satisfaction instruments should be subjected to the same
      psychometrically rigorous standards and procedures as any other patient-reported
      outcome and should also be subject to the same regulatory standards as other
      patient-reported outcomes with respect to advertising and promotion.

PMID- 15164812
TI  - Overuse of the term "nonconvulsive status epilepticus".

PMID- 15164813
TI  - The EEG profile of patients with uncontrolled vs. controlled seizures.
AB  - The goal of this study was to provide an EEG profile of patients (150) with
      uncontrolled (U) seizures, in contrast with those (150) with controlled (C)
      attacks. In the U group 804 EEGs were done and in the C group 674 were performed,
      all with both waking and sleep recordings; the range of EEG records on a given
      patient was 2-23. The number of spikes and the amount of abnormal slowing was
      quantified in each record. Two different peaks of age were evident, appearing at
      10-19 yrs and 40-49 yrs. The number of patients with a spike discharge on the
      first EEG was 64% in the C and 92% in the U group with an increasing incidence to
      83% (C) and 100% (U) in later records. If spikes were absent in the first EEG in
      the C group, the majority showed only rare discharges later. The spike profile of
      the U patient initially was that 1/2 showed a typical number of spikes and nearly
      1/2 many or very many spikes. Over time a decrease was seen in those with many
      very many discharges, resulting in an increase with a typical number. Still
      later, a reversal occurred in the U patients with an increasing number with many
      or very many spikes. The slow wave profile of the U patient was that 2/3 showed
      some abnormal slow waves on the first record, increasing to 100% in later
      records. The increase was from delta, not theta activity. The spike profile of
      the C patient was that a typical number of spikes was seen at first in nearly
      1/2, but only a small minority showed many-very many discharges. The slow wave
      profile for the C patient was that theta, not delta waves, increased in time. The
      (median) time between a unilateral spike discharge to a bilateral discharge was 4
      5 yrs, and the U group much more often than the C group showed this change to
      bilateral spikes. The time between unilateral to bilateral slow waves varied
      between 4-9 yrs.

PMID- 15164814
TI  - Event-related potentials elicited by visual stimulus-duration discrimination
      tasks.
AB  - Event-related potentials (ERPs) were recorded on subjects who discriminated the
      stimulus duration of two sequentially presented spots (S1 and S2). Four kinds of
      trials were included: short-duration match (S1 and S2 lasting 300 ms), short
      duration conflict (S1 and S2 lasting 300 ms and 600 ms, respectively), long
      duration match (S1 and S2 were 600 ms) and long-duration conflict (S1 and S2 were
      600 ms and 900 ms, respectively). When S1 was equal to S2, components of P1, N1,
      P2, N2 and a delayed late positive component were recorded after the onset of S2.
      The other three negativities were elicited in both short and long duration
      conflict conditions. The three negative components peaked at 475, 600 and 900 ms
      in the short-duration condition, and they peaked at 805, 900 and 1200 ms in the
      long-duration condition. The first negativity was considered a visual mis-match
      negativity (vMMN), followed by a delayed N270 reflecting the conflict processing
      for duration in the brain. The last negativity, similar to N270, possibly
      reflects the second conflict processing activity evoked by stimulus offset.

PMID- 15164815
TI  - "Mu rhythm status" and clinical correlates.
AB  - Rolandic mu rhythm is usually limited to brief stretches of 0.5 to 2 sec
      duration. Two observations of status-like enhancement of mu rhythm have prompted
      this report. In both cases, 4-hour EEG-Video-Monitoring was used. Clinically, the
      reported cases differed considerably. Case 1 showed nearly continuous mu activity
      associated with general motionlessness: akinesia/amimia but without rigidity,
      caused by frontal lobe impairment due to multiple sclerosis. In Case 2, an
      impressive mu-status started in drowsiness and was presumably attributable to
      levitiracetam (which had rendered seizure-free the patient's formerly severe case
      of temporal lobe epilepsy). Mu rhythm status, thus far, is an unknown EEG entity.
      It can be caused by impaired fronto-motor input and may also constitute a
      medication-effect (levitiracetam).

PMID- 15164816
TI  - Structural lesions in periodic lateralized epileptiform discharges (PLEDs).
AB  - In this study we investigated the structural lesions of patients with periodic
      lateralized epileptiform discharges (PLEDs) to determine the possible
      relationship of lesions to PLEDs' localization on EEG and to metabolic
      abnormality. Clinical findings and electroencephalography (EEG), computerized
      tomography (CT) and magnetic resonance imaging (MRI) of the 71 adult patients
      with PLEDs were evaluated. Stroke, herpes encephalitis and intracranial tumor or
      abscess were the most common etiological factors. Cortical gray matter and
      adjacent subcortical white matter lesions were detected in 64.7%, cortical gray
      matter lesions in 11.3% and subcortical white matter lesions in 4.2% of the
      patients. Although it is thought that PLEDs occur mostly with acute lesions,
      chronic lesions causing PLEDs were found in 35.2% of the patients. Bilateral
      lesions were detected in 19.7% and 33.8% of the patients had metabolic
      abnormality. PLEDs localized the region of the lesion in 63.4% of the patients.
      PLEDs are usually self-limited features, but chronic PLEDs were detected in 5
      patients in this study. Acute structural lesions involving cortical gray matter
      with adjacent subcortical white matter were found in most of the patients with
      PLEDs, but the lesion localization and age, acute or chronic, varied.

PMID- 15164817
TI  - Benign focal epilepsy of childhood: epileptic seizure during somatosensory evoked
      potential: a case report.
AB  - A 6-year-old girl with a history of partial seizures had parietal spontaneous
      spikes, and high-voltage paroxysms, evoked by tapping of the hands and feet, in
      the parietal contralateral region during the electroencephalogram. The girl
      underwent a somatosensory evoked potential study, when she had a seizure, with
      tonic contraction rising of the right leg then followed by clonic jerks of the
      right leg, version of the head to the right, followed by a tonic contraction of
      the ipsilateral arm with flexion at the elbow. The seizure lasted 20-30 seconds.
      We believe this is the first description of a seizure during a somatosensory
      evoked potential procedure.

PMID- 15164818
TI  - Tonic-clonic seizures in a patient with primary hypoparathyroidism: a case
      report.
AB  - Hypoparathyroidism, a life threatening disorder, occurs when insufficient
      parathyroid hormone is produced to maintain extracellular calcium levels within
      the normal range. The acute clinical signs and symptoms of hypoparathyroidism are
      the same as those of hypocalcemia, ranging from tingling to intractable
      generalized tonic-clonic seizures; therefore, it can be mistaken for epilepsy. We
      report the case of a 36-year-old man who presented two tonic-clonic seizures,
      characterized by sudden loss of consciousness with a fall and diffuse tonic
      contractions and clonic jerks. At first diagnosis of epilepsy was established and
      therapy with valproate was commenced. In the following days, the patient
      presented typical signs of hypocalcemia and the diagnosis of hypoparathyroidism
      was made. In the 4 months follow up, antiepileptic drug therapy was reduced until
      suspension and calcium supplementation was initiated. We briefly review the most
      recent reports in the literature.

PMID- 15164819
TI  - Encephalopathy secondary to imipenem therapy.
AB  - We describe the case of an 84-year-old woman who developed a confusional state
      and suffered from a generalized tonic-clonic seizure while she was treated with
      imipenem, a beta-lactam antibiotic. Focal and generalized epileptiform discharges
      and a photoparoxysmal response were prominent with transient changes on the EEG.

PMID- 15164820
TI  - Quantitative EEG findings of a temporal lobe abnormality not detected by magnetic
      resonance or SPECT imaging in a patient with dementia.
AB  - The last three decades have seen significant advances in structural neuroimaging
      techniques such as computerized tomography and magnetic resonance imaging. These
      seem to have surpassed EEG as modalities for the identification of focal CNS
      lesions. Reported here is the case of a patient with a temporal lobe lesion not
      evident with magnetic resonance imaging or single photon emission computerized
      tomography but detected by EEG and positron emission tomography. EEG,
      particularly quantitative EEG, remains a valuable tool for the demonstration of
      the degree of dysfunctional changes associated with a cerebral lesion.

PMID- 15164821
TI  - Quantitative electroencephalography in frontotemporal dementia with
      methylphenidate response: a case study.
AB  - Frontotemporal dementia is an underdiagnosed illness with predominant behavioral
      and executive manifestations. Historically, diagnosis has been based on a
      combination of clinical history, neuropsychological testing, and brain imaging.
      No effective treatment currently exists for this disorder. A case is presented
      using quantitative EEG with methylphenidate challenge correlated with SPECT. The
      patient underwent neuropsychological testing, a SPECT brain study, and a
      quantitative EEG, which was repeated after methylphenidate administration. SPECT
      was significant for hypoperfusion to the bilateral frontotemporal regions, with
      left-sided hypoperfusion greater than homologous right as demonstrated by LORETA
      analysis. QEEG correlated with SPECT, and demonstrated profound left greater than
      right bi-frontotemporal slowing, which normalized partially after methylphenidate
      administration. The patient has remained on methylphenidate as an outpatient, and
      has had significant behavioral improvement. Quantitative EEG may provide both
      diagnostic and therapeutic data with regard to frontotemporal dementia. Further
      studies of methylphenidate in this population are needed to confirm these data.

PMID- 15164822
TI  - The electrocerebellogram.
AB  - A revisitation of EEG studies derived experimentally from the cerebellum confirms
      the predominance of ultrafast activities but also shows various degrees of
      underlying slower frequencies (from the beta down to the delta range). Earlier
      personal work was based upon recording from the human cerebellum (and especially
      from fastigial and dentate nucleus) in connection with therapeutic cerebellar
      electrical stimulation. These patients suffered from intractable seizures
      (advanced cases of Lennox-Gastaut syndrome). Naturally, our recording technique
      in 1974 excluded the ultrafast range above 80/sec but failed to show activities
      in the upper beta range. In these cases, the severity of the seizure disorder
      caused structural impairment and ictal activity invaded the cerebellum. The
      electrocerebellogram is still insufficiently understood. An attempt at an
      analysis of known facts is being made. Further research in this field is needed.

PMID- 15164823
TI  - 'Computation of HORRAT values".

PMID- 15164824
TI  - Inductively coupled plasma-optical emission spectrometry and -mass spectrometry.

PMID- 15164825
TI  - Determination of tylosin in feeds by liquid chromatography with solid-phase
      extraction.
AB  - A method was developed for the determination of tylosin in feeds. The method
      involves extraction of tylosin with methanol, concentration under a stream of
      nitrogen, and cleanup using Phenomenex C18 solid-phase extraction cartridge.
      Analyte separation and quantitation were achieved by gradient reversed-phase
      liquid chromatography and UV absorbance at 285 nm with a reference wavelength of
      320 nm with column temperature of 45 degrees C. Average spike recoveries for
      samples prepared at 4 spiking levels (22.7, 181, 907, and 1000 g/ton) were 111.0,
      94.9, 96.2, and 98.6%, respectively. The overall method precision at each of the
      4 spiking levels was < or = 7.85% relative standard deviation. The limits of
      detection and quantitation (g/ton) were 2.16 and 7.20 g/ton, respectively.

PMID- 15164826
TI  - Liquid chromatographic determination of urea in water-soluble urea-formaldehyde
      fertilizer products and in aqueous urea solutions: collaborative study.
AB  - Water soluble urea-formaldehyde (UF) fertilizers, manufactured by complex
      reaction of urea and formaldehyde, typically contain varying amounts of unreacted
      urea. A liquid chromatography method for the analysis of urea in these products,
      and in aqueous urea solutions, was collaboratively studied. An amine
      chromatography column was used to separate the unreacted urea from numerous UF
      reaction products present in these liquid fertilizers. Unreacted urea was
      determined by using external urea standards with UV detection at 195 nm. The
      standards and test samples were prepared in the mobile phase of 85% (v/v)
      acetonitrile in water. Ten laboratories analyzed 5 different UF-based commercial
      products containing unreacted urea in the range of 6 to 17% by weight, and 5
      different concentrations of urea in water equivalent to commercial products of
      that nature. The aqueous urea solutions contained 2-20% urea (w/w). The range of
      s(R) values for the 5 UF-based commercial fertilizers was 0.49-1.02 and the
      %RSD(R) was 1.94-6.14. The s(R) range for the 5 urea solutions was 0.10 to 0.79
      and the %RSD(R) range was 2.54 to 4.88. The average recovery of urea from the
      aqueous urea solutions was 96-103%. Therefore, this method is capable of
      monitoring urea nitrogen manufacturers' label claims and total nitrogen claims in
      those cases where urea is the sole source of plant food nitrogen. Based on the
      collaborative study data, the authors recommend this method be approved for AOAC
      Official First Action status.

PMID- 15164827
TI  - Kinetic spectrophotometric determination of josamycin in formulations and spiked
      human plasma using 3-methylbenzothiazolin-2-one hydrazone/Fe+3 system.
AB  - A simple kinetic spectrophotometric method was developed for the determination of
      josamycin in its dosage forms and spiked human plasma. The method is based on
      reaction of the drug with 3-methylbenzothiazolin-2-one hydrazone/ferric chloride
      system for a fixed time of 20 min at 70 degrees C and measuring the produced
      color at 665 nm. The absorbance-concentration plot is rectilinear over the range
      of 5.0-30.0 microg/mL with detection limit of 1.0 microg/mL (1.2 x 10(-6) M). The
      determination of josamycin by the fixed concentration and the rate-constant
      methods is also feasible with the calibration equations obtained, but the fixed
      time method proved to be more applicable. The procedure was successfully applied
      to commercial tablets. The results obtained were favorably compared with those
      given by reference methods. The method was further extended to the in vitro
      determination of josamycin in spiked human plasma. The recovery (n = 8) was
      100.76 +/- 3.43%. The stoichiometry of the reaction between the drug and the
      reagent was studied by adopting the limiting logarithmic method, and a proposal
      of the reaction pathway was presented.

PMID- 15164828
TI  - Multicomponent quantitative resolution of binary mixtures by using continuous
      wavelet transform.
AB  - Continuous 1-dimensional wavelet transform (WT) was applied to the quantitative
      analysis of a vitamin combination of thiamine hydrochloride (THI) and pyridoxine
      hydrochloride (PYR) with strongly overlapping signals. Absorbance data from the
      UV-Vis absorption spectrum of width 1150 were subjected to Gauss1 and Gauss2 WTs.
      Because of its flexibility, data processing, and its high signal amplitude, the
      continuous WT method is a powerful tool for analysis of multicomponent mixtures.
      By measuring the amplitude signals corresponding to the selected zero-crossing
      points of the transformed signal, we obtained the calibration curve. The
      validation of the calibration graphs was confirmed with different mixtures of THI
      and PYR at various concentration ratios. A brief explanation of the continuous
      wavelet method is given. MATLAB 6.5 software was used to perform the
      calculations. The results of our study were compared with those obtained by
      spectroscopic, chemometric, and liquid chromatographic methods, and good
      agreement was found.

PMID- 15164829
TI  - Stability-indicating chromatographic methods for the determination of some
      oxicams.
AB  - Two sensitive and selective methods were developed for the determination of some
      oxicams, namely, lornoxicam (LOX), tenoxicam (TEX), and meloxicam (MEX), in the
      presence of their alkaline degradation products. The first method is based on the
      thin-layer chromatographic separation of the 3 drugs from their alkaline
      degradation products, followed by densitometric measurement of the intact drug
      spots for LOX, TEX, and MEX at 380, 370, and 364 nm, respectively. The developing
      systems used for separation are ethyl acetate-methanol-26% ammonia (17 + 3 +
      0.35, v/v/v) for LOX and TEX and chloroform-n-hexane-96.0% acetic acid (18 + 1 +
      1, v/v/v) for MEX. The linear ranges were 0.25-6.0 microg/spot for LOX and TEX
      and 0.5-10 microg/spot for MEX, with mean recoveries of 99.80 +/- 1.32, 100.57 +/
      1.34, and 100.71 +/- 1.57%, respectively. The second method is based on the
      liquid chromatographic separation of the 3 drugs from their alkaline degradation
      products on a reversed-phase C18 column, using mobile phases of methanol
      acetonitrile-acetate buffer, pH 4.6 (4.5 + 0.5 + 5.0, v/v/v) for LOX and MEX and
      methanol-acetonitrile-acetate buffer, pH 4.6 (1.9 + 0.1 + 3.0, v/v/v) for TEX at
      ambient temperature. Quantification is achieved by UV detection at 280 nm, based
      on peak area. The linear ranges were 0.5-20 microg/mL for LOX and TEX and 1.25-50
      microg/mL for MEX, with mean recoveries of 99.81 +/- 1.01, 98.90 +/- 1.61, and
      100.86 +/- 1.55%, respectively. The methods were validated according to
      guidelines of the International Conference on Harmonization. The developed
      methods were successfully applied to the determination of LOX, TEX, and MEX in
      bulk powder, laboratory-prepared mixtures containing different percentages of
      degradation products, and pharmaceutical dosage forms.

PMID- 15164830
TI  - Validation study to demonstrate the equivalence of a minor modification (TECRA
      ULTIMA protocol) to AOAC Method 998.09 (TECRA Salmonella Visual Immunoassay) with
      the cultural reference method.
AB  - The TECRA Salmonella Visual Immunoassay (VIA) using Rappaport-Vassiliadis RV[R10]
      as a single selective enrichment broth has Final Action approval (AOAC Method
      998.09). TECRA has recently developed a protocol (TECRA ULTIMA), which involves
      the addition of a new additive to a 1 mL aliquot of the RV[R10] broth, prior to
      the heat-killing step, thereby allowing the RV[R10] broth to be tested directly
      in the kit and thus eliminating the need for the 2 h post-enrichment in M broth.
      An in-house validation study was conducted to compare the modified AOAC Method
      998.09 to the reference culture method. Three foods were used in the study:
      Naturally contaminated raw ground poultry at high (10-50 cells/25 g), and low (1
      5 cells/25 g) levels; and milk powder and peanut butter, artificially inoculated
      at low and high levels with Salmonella bovismorbificans and S. enterica Mbandaka,
      respectively. Twenty test portions were analyzed for each level with 10
      uninoculated control samples per food. Overall, no significant differences (p
      <0.05) were observed when the proportion of positive test portions for the
      modified VIA were compared with that for the reference method. This minor
      modification, which employs the additive (provided in the TECRA ULTIMA SALMONELLA
      Test Kit) to permit the direct analysis of RV[R10] broth has demonstrated the
      utility of the TECRA ULTIMA SALMONELLA protocol. It is recommended that the minor
      modification to Method 998.09 be approved First Action as an additional option
      within the method.

PMID- 15164831
TI  - Evaluation of VIDAS Immuno-Concentration Salmonella (ICS) plus selective plate
      method (Hektoen enteric, bismuth sulfite, Salmonella identification) for
      detection of Salmonella in selected foods (Method Modification 2001.07):
      collaborative study.
AB  - A new method for detection of Salmonella in foods in 48 h has been granted AOAC
      First Action approval in selected foods (Official Method 2001.07) using both the
      VIDAS Immuno-Concentration Salmonella (ICS) method and a combination of 3
      selective plates: Hektoen enteric (HE), bismuth sulfite (BS), and Salmonella
      Identification (SMID).

PMID- 15164832
TI  - Evaluation of VIDAS Immuno-Concentration Salmonella (ICS) plus selective plate
      method (Hektoen enteric, bismuth sulfite, xylose lysine desoxycholate) for
      detection of Salmonella in selected foods (Method Modification 2001.08):
      collaborative study.
AB  - A new method for detection of Salmonella in foods in 48 h has been granted AOAC
      First Action approval in selected foods (Official Method 2001.08) using both the
      VIDAS Immuno-Concentration Salmonella (ICS) method and a combination of 3
      selective plates: Hektoen enteric (HE), bismuth sulfite (BS), and xylose lysine
      desoxycholate (XLD).

PMID- 15164833
TI  - Evaluation of VIDAS Immuno-Concentration Salmonella (ICS)/VIDAS Salmonella (SLM)
      immunoassay method for detection of Salmonella in selected foods (Method
      Modification 2001.09): collaborative study.
AB  - A new method for detection of Salmonella in foods in a minimum of 24 h was
      adopted as an AOAC Official First Action Method for selected foods (2001.09)
      using both the VIDAS Immuno-Concentration Salmonella (ICS) and VIDAS Salmonella
      (SLM) methods.

PMID- 15164835
TI  - Simultaneous determination of aflatoxins, ochratoxin A, and zearalenone in grains
      by new immunoaffinity column/liquid chromatography.
AB  - The simultaneous determination of mycotoxins was performed in 3 steps:
      extraction, cleanup, and detection. For extraction, a mixture of acetonitrile
      water (60 + 40, v/v) was proved appropriate. For cleanup, a new Afla-Ochra-Zea
      immunoaffinity column was used. After derivatization with trifluoroacetic acid,
      the mycotoxins aflatoxins, ochratoxin A (OTA), and zearalenone (ZEA) were
      determined simultaneously by liquid chromatography with fluorescence detection.
      The detection limits in different matrixes after cleanup with the new
      immunoaffinity column were very low: aflatoxins, 0.002-0.7 microg/kg; OTA, 0.07
      0.25 microg/kg; ZEA, 1-3 microg/kg. The limits of determination were: aflatoxins,
      0.25 microg/kg; OTA, 0.5 microg/kg; ZEA, 5 microg/kg. The recovery rates for
      aflatoxins, OTA, and ZEA for rye and rice were between 86 and 93% when a 0.5 g
      sample matter per immunoaffinity column was used.

PMID- 15164834
TI  - Evaluation of the BAX system for detection of Listeria monocytogenes in foods:
      collaborative study.
AB  - A multilaboratory study was conducted to compare the automated BAX system and the
      standard cultural methods for detection of Listeria monocytogenes in foods. Six
      food types (frankfurters, soft cheese, smoked salmon, raw, ground beef, fresh
      radishes, and frozen peas) were analyzed by each method. For each food type, 3
      inoculation levels were tested: high (average of 2 CFU/g), low (average of 0.2
      CFU/g) and uninoculated controls. A total of 25 laboratories representing
      government and industry participated. Of the 2335 samples analyzed, 1109 were
      positive by the BAX system and 1115 were positive by the standard method. A Chi
      square analysis of each of the 6 food types, at the 3 inoculation levels tested,
      was performed. For all foods, except radishes, the BAX system performed as well
      as or better than the standard reference methods based on the Chi square results.

PMID- 15164836
TI  - Qualitative method for determination of aflatoxin B1 in nuts.
AB  - The proper characterization of a commercial qualitative method for determining
      aflatoxin B1 in some nuts is described. A qualitative method that provides binary
      responses of the yes/no type means that the performance parameters have been
      properly adapted and defined. Performance characteristics such as the cut-off
      limit, the detection limit, sensitivity, specificity, false-positive and negative
      rates, and the unreliability or uncertainty region are defined and then estimated
      by means of the performance characteristic curves. The commercial test kit showed
      the cut-off limit at 1.6 ng/g, with a sensitivity rate of 95% and a false
      negative rate of zero. A modification can be performed to shift the cut-off to
      2.0 ng/g, keeping the same values for the sensitivity and false-negative rate.

PMID- 15164837
TI  - Preparation of peanut butter suspension for determination of peanuts using enzyme
      linked immunoassay kits.
AB  - Peanuts are one of the 8 most common allergenic foods and a large proportion of
      peanut-allergic individuals have severe reactions, some to minimal exposure.
      Specific protein constituents in the peanuts are the cause of the allergic
      reactions in sensitized individuals who ingest the peanuts. To avoid accidental
      ingestion of peanut-contaminated food, methods of analysis for the determination
      of the allergenic proteins in foods are important tools. Such methods could help
      identify foods inadvertently contaminated with peanuts, thereby reducing the
      incidence of allergic reactions to peanuts. Commercial immunoassay kits are
      available but need study for method performance, which requires reference
      materials for within- and between-laboratory validations. In this study, National
      Institute of Standards and Technology Standard Reference Material 2387 peanut
      butter was used. A polytron homogenizer was used to prepare a homogenous aqueous
      Peanut Butter suspension for the evaluation of method performance of some
      commercially available immunoassay kits such as Veratox for Peanut Allergen Test
      (Neogen Corp.), Ridascreen Peanut (R-Biopharm GmbH), and Bio-Kit Peanut Protein
      Assay Kit (Tepnel). Each gram of the aqueous peanut butter suspension contained
      20 mg carboxymethylcellulose sodium salt, 643 microg peanut, 0.5 mg thimerosal,
      and 2.5 mg bovine serum albumin. The suspension was homogenous, stable,
      reproducible, and applicable for adding to ice cream, cookies, breakfast cereals,
      and chocolate for recovery studies at spike levels ranging from 12 to 90
      microg/g.

PMID- 15164838
TI  - Studies of polyester fiber as carrier for microbes in a quantitative test method
      for disinfectants.
AB  - Tests were conducted by a Task Force on Disinfectant Test Methods that was
      appointed to investigate controversies regarding the accuracy of AOAC test
      methods for disinfectants as presented in AOAC's Official Methods of Analysis,
      Chapter 6. The general principles for new and improved AOAC tests are discussed,
      and a disinfectant test using microbes labeled onto a polyester fiber surface is
      described. The quantitative test measures the survival of test microbes as a
      function of exposure time as well as the exposure conditions required to kill 6
      log10 of the test microbes. The time required was similar to that for the
      kinetics of the kill of Bacillus subtilis-labeled cylinders as tested by methods
      of the AOAC Sporicidal Test 966.04.

PMID- 15164839
TI  - Determination of fluquinconazole, pyrimethanil, and clofentezine residues in
      fruits by liquid chromatography with ultraviolet detection.
AB  - A simple method was developed for the determination of fluquinconazole,
      pyrimethanil, and clofentezine in whole fruit; peel; and pulp of mango, apple,
      and papaya. These compounds were extracted from fruit samples with a mixture of
      ethyl acetate-n-hexane (1 + 1, v/v). An aliquot (2 mL) of the extract was
      evaporated to near dryness under a stream of nitrogen, and the residue was
      dissolved with 2 mL methanol. The analysis was performed by means of liquid
      chromatography with ultraviolet detection at 254 nm using a gradient solvent
      system. The method was validated with fortified fruit samples at concentration
      levels of 0.05, 0.10, 0.20, and 0.50 mg/kg. Average recoveries (4-8 replicates)
      ranged from 80 to 95% with relative standard deviations between 3.5 and 12.7%.
      Detection limits ranged from 0.03 to 0.05 mg/kg for fruit pulp and 0.03 mg/kg for
      whole fruit. The quantitation limits ranged from 0.05 to 0.10 mg/kg for fruit
      pulp and 0.05 mg/kg for whole fruit. The analytical method was applied to fruit
      samples obtained from local markets.

PMID- 15164840
TI  - Accurate and reproducible methods for analysis of sterol oxidation products in
      foods: an overview.

PMID- 15164841
TI  - Analysis of sterol oxidation products in foods.
AB  - The main aspects related to the analysis of sterol oxidation products (SOP) in
      foods are comprehensively reviewed. Special emphasis is placed on the critical
      and controversial points of this analysis because these points affect crucial
      analytical parameters such as precision, accuracy, selectivity, and sensitivity.
      The effect of sample preparation and the conditions of quantification by gas
      chromatography and liquid chromatography on these parameters are also reviewed.
      The results show that, in order to choose an adequate method to analyze SOP in a
      certain food, the analyst must consider its SOP concentration and matrix
      complexity. The term SOP includes both cholesterol oxidation products (COP) and
      phytosterol oxidation products (POP). The state of the art of COP and POP
      analysis is quite different; many more studies have dealt with the analysis of
      COP than of POP. However, most of the results presented here about COP analysis
      may be extrapolated to POP analysis because both groups of compounds show similar
      structures and characteristics.

PMID- 15164842
TI  - Analysis of cholesterol oxidation products in biological samples.
AB  - Cholesterol oxidation products, or oxysterols, have gained increased attention
      since it was suggested that they participate in cell signaling as ligands for the
      nuclear receptors liver X receptor alpha and beta. In addition, oxysterols serve
      as important intermediates in bile acid biosynthesis and are also involved in
      cholesterol transport. Several studies have suggested that certain oxysterols may
      be used as markers for oxidative stress, and still other oxysterols may be of use
      in diagnosing neurological diseases. This broad spectrum of functions in health
      and disease has created a demand for accurate and reliable methods to measure
      oxysterols in complex biological matrixes. At present, the most reliable and
      sensitive method for oxysterol determination in biological materials is isotope
      dilution gas chromatography-mass spectrometry using deuterium-labeled internal
      standards. With this technique, the major oxysterols in human blood plasma and
      atherosclerotic plaques have been carefully determined. The knowledge of
      oxysterol contents in other tissues and organs is still very scarce. As
      oxysterols are found to participate in an increasing number of cellular events,
      it is obvious that improved methods are needed for their analysis to understand
      their roles in the living cell.

PMID- 15164843
TI  - Comparison of cholesterol oxidation product preparation methods for subsequent
      gas chromatographic analysis.
AB  - An evaluation was made of the stability of cholesterol hydroperoxides (CHPs)
      under the analytical conditions and preparation methods commonly used for
      determination and quantification of cholesterol oxidation products (COPs). CHPs
      were prepared by photoxidation and separated by silica thin-layer chromatography.
      CHPs were individually collected by normal-phase liquid chromatography and then
      subjected either to reduction or to cold saponification. The corresponding
      hydroxyl derivatives were generated by reduction, whereas cold saponification
      gave rise predominantly to 7-ketocholesterol. In another test, silylated and non
      silylated CHPs were separately injected into a gas chromatograph at 310 degrees
      C, collected, and re-injected into a gas chromatography-mass spectrometry system.
      The silylated CHPs were more stable than the non-silylated ones, giving 7
      ketocholesterol, 7alpha- and 7beta-hydroxycholesterol as main degradation
      products. Two unknown degradation peaks were detected in both silylated and
      nonsilylated CHPs, having 384 as main m/z fragment. The study of their mass
      spectra led to the conclusion that peaks A and B correspond to 6alpha- and 6beta
      hydroxycholesterol, respectively.

PMID- 15164844
TI  - New internal standard for quantitative determination of oxyphytosterols by gas
      chromatography.
AB  - A study was conducted to develop a new internal standard for the quantitative
      determination of oxyphytosterols. Tests on 5-androsten-3beta,17beta-diol; 5alpha
      androstan-3beta,17beta-diol; 5-pregnen-3beta,20alpha-diol; and 5alpha-pregnan
      3beta,20beta-diol showed that these compounds were not fully adequate. However,
      the compound 3beta,22-dihydroxy-20-homo-5-pregnene, synthesized in 4 steps,
      resulted in a promising internal standard, with a molecule similar to
      hydroxysterols; retention time as trimethylsilyl in gas chromatography comprised
      between 5alpha-cholestane and 7alpha-hydroxycholesterol; clear mass spectrum in
      electronic impact mass spectrometry, with several intense ions suitable for
      selected ion monitoring-mass spectrometry. Further studies are necessary to
      observe the behavior of these compounds during the entire analytical procedure.

PMID- 15164845
TI  - Determination of plant sterol oxidation products in plant sterol enriched
      spreads, fat blends, and plant sterol concentrates.
AB  - Plant sterols (PS) are very stable molecules but may undergo oxidation due to the
      presence of a double bond in the ring structure. In order to assess whether this
      occurs during heating and storage, an analytical procedure was developed for the
      determination of concentration levels and identity of PS oxidation products in
      functional food ingredients and products. The method is based on cold
      saponification, solvent extraction of unsaponifiables, isolation of sterol
      oxidation products by means of liquid chromatography, and final analysis by gas
      chromatography (GC) with flame ionization detection. Identification of the key PS
      oxidation products was performed by means of GC-mass spectrometry (GC-MS).
      Isotope dilution MS was used to verify the absence of the formation of potential
      artifacts by the method. The method described is applicable to spreads
      (containing 20-65% water), oils, sterol esters, pure sterols, and fat extracts
      from food. The between-day reproducibility of the total content of sterol
      oxidation products in control samples sample was 8%, and of individual sterol
      oxidation products, 6-15%. The recovery of sterol oxidation products was 91%. The
      limit of detection was 0.1 mg/kg.

PMID- 15164846
TI  - Artifactual oxidation of cholesterol during the analysis of cholesterol oxidation
      products: protective effect of antioxidants.
AB  - To study the influence of the addition of various antioxidants and their
      combinations on the artifactual oxidation of cholesterol during analysis, 2
      factorial experiments were performed in duplicate. In the first experiment, 2
      amounts of the following antioxidants were assayed: ethylenediaminetetraacetic
      acid (EDTA) disodium salt (0 and 1 mg), pyrogallol (0 and 600 microg), and
      butylated hydroxytoluene (BHT; 0 and 600 microg); in the second, EDTA disodium
      salt (0 and 1 mg), ascorbyl palmitate (0 and 600 microg), and BHT (0 and 600
      microg). Under low oxidative conditions of dim light, evaporation of solvents at
      low temperatures, and cold saponification in darkness under nitrogen atmosphere,
      the addition of antioxidants showed no further protective effect. Furthermore,
      the presence of ascorbyl palmitate significantly increased the formation of
      cholesterol-5beta,6beta-epoxide, and 7beta-hydroxycholesterol.

PMID- 15164848
TI  - Cholesterol oxidation in meat-based baby foods.
AB  - Cholesterol oxidation in commercial meat-based homogenized and freeze-dried baby
      foods was examined. The 7 major products of this reaction were determined by gas
      chromatography coupled with mass spectrometry (GC-MS). As far as single
      cholesterol oxidation products (COP) are concerned, 7-ketocholesterol was the
      major product of direct cholesterol oxidation in the 2 groups of analyzed
      samples, and this study confirmed that it is a useful marker of the whole
      cholesterol oxidation process. Nevertheless, the amounts of cholesterol
      5beta,6beta-epoxide were often similar to and sometimes higher than the amounts
      of 7-ketocholesterol, thus showing a strong development of both direct and
      indirect cholesterol oxidation pathways. Total COP content was significantly
      higher in freeze-dried than in homogenized products. Moreover, in freeze-dried
      samples, the COP content per serving was quite variable and, in 2 samples, it was
      close to or even higher than 500 microg. The greater development of cholesterol
      oxidation in the freeze-dried samples was confirmed by their highest total
      COP/cholesterol percent ratios. A constant correlation between the fatty acid
      composition and the development of cholesterol oxidation was not found, although
      a positive correlation between unsaturated fatty acid content and total COP
      content occasionally exists in samples of the same brand.

PMID- 15164847
TI  - Inhibition of stigmasterol oxidation by antioxidants in purified sunflower oil.
AB  - A study was conducted to analyze the effect of the antioxidants butylated
      hydroxytoluene, alpha-tocopherol, ethanolic extracts of rosemary, and green tea
      on stigmasterol resistance against degradation and formation of its oxidation
      products in purified triacylglycerols (TAG) from sunflower oil. The content of
      stigmasterol and its oxidation products 7alpha- and 7beta-hydroxy, alpha- and
      beta-epoxy, triol, and 7-ketostigmasterol were determined during incubation at 60
      degrees C for 3, 6, and 9 days. In addition, peroxide value and fatty acid
      composition were also determined in the samples. Correlation between the levels
      of the accumulated stigmasterol oxides and peroxide value of the TAG with
      antioxidants during incubation was significant only for rosemary extract (R =
      0.6799, p < 0.05). The lack of correlation precludes the use of peroxide values
      to determine the level of sterol oxidation products in the used model system.
      Correlation between stigmasterol content and the level of stigmasterol oxides was
      significant for all samples (R = 0.8874, p < 0.05). The total increase of the
      stigmasterol oxidation products was the lowest in samples with alpha-tocopherol,
      but the content of stigmasterol-triol increased the most in this sample. In all
      the analyzed samples, alpha-epoxy-stigmasterol was formed in the highest amounts
      among the analyzed stigmasterol oxidation products.

PMID- 15164849
TI  - Harmonization of methods for analysis of cholesterol oxides in foods--the first
      portion of a long road toward standardization: interlaboratory study.
AB  - A compilation of literature data on the content of cholesterol oxidation products
      (COP) in various food products and in blood demonstrates a large variation in
      content in products or tissues of very similar nature when analyzed in different
      laboratories according to a large number of methods. The lack of validated,
      internationally recognized methodology with published accuracy and precision has
      so far hindered such assessments. Hence an interlaboratory comparision of
      methodologies of COP analysis was undertaken on egg yolk powders (EYP), whole
      milk powders (WMP), skim milk powders (SMP), and lard (L). Each product type had
      one fresh sample (low) and one aged (high) in COP contents. A total of 17 sets of
      results on WMP, 15 on SMP and EYP, and 13 on L were compared. Overall results
      (mg/kg sample) varied extensively: Fresh EYP 0.72-265, aged EYP 2.51-361; fresh
      WMP 0.02-18.1, aged WMP 0.02-26.9; fresh SMP 0.02-6.51, aged SMP <0.01-6.51;
      fresh L 0.18-97, aged L 4.15-452. Some results were questioned, viz., those from
      laboratories not indicating substantial differences between samples "low" and
      "high" in total COP. Others were excluded because of lack of verification of
      identity of gas chromatographic peaks by mass spectrometry. Then a more narrow
      range of core results (mg/kg sample) was observed: Fresh EYP 5.69-29.5 sample,
      aged EYP 11.8-79.0; fresh WMP 0.12-1.76, aged WMP 1.17-13.7; fresh SMP <0.30
      <1.21, aged SMP 0.30-2.26; fresh L 0.18-5.07, aged L 94.4-231. At a workshop
      discussing the results, numerous recommendations were made toward more reliable
      methodology for determination of COP in foods.

PMID- 15164850
TI  - Reliable methods for the determination of trans fatty acids and conjugated
      linoleic acid isomers: an overview.

PMID- 15164851
TI  - Overview of methods for the determination of trans fatty acids by gas
      chromatography, silver-ion thin-layer chromatography, silver-ion liquid
      chromatography, and gas chromatography/mass spectrometry.
AB  - trans Isomers of naturally occurring cis-unsaturated fatty acids are produced
      when liquid vegetable oils or marine oils are partially hydrogenated to produce
      margarine, shortenings, and other hardened-fat products. Isomeric trans fatty
      acids are also formed in the intestinal tract of ruminants, and they appear in
      small amounts in dairy products and ruminant meat. Currently, satisfactory
      analyses for the fatty acid profiles of fats containing trans fatty acids are
      obtained by gas chromatography (GC) using capillary columns coated with highly
      polar cyanosilicone stationary phases. In capillary GC methods, the key
      limitation has been the incomplete separation of trans-monoenoic acid isomers
      from their cis isomers; however, recent reports have demonstrated that
      improvements in separation are attainable with the use of 100 m columns. In these
      columns, there is very little overlap of cis and trans isomers. More accurate
      trans fatty acid analyses can be obtained by coupling GC with either silver
      nitrate thin-layer chromatography or silver-nitrate liquid chromatography.

PMID- 15164852
TI  - Overview of infrared methodologies for trans fat determination.
AB  - trans Fatty acids are present in a variety of foods like dairy products, but the
      major sources are products that contain commercially hydrogenated fats. Some
      studies have shown that trans fatty acids elevate levels of serum low-density
      lipoprotein (LDL)-cholesterol and lower high-density lipoprotein (HDL)
      cholesterol. The quantitation and identification of trans fatty acid isomers is
      difficult because of the wide range of positional monoene, diene, and triene
      fatty acid isomers present in hydrogenated oils. This is complicated by the cis
      positional isomers that are also present, as well as the lack of commercial
      chromatographic standards for many fatty acid isomers. In this review, infrared
      methodologies for the determination of total trans fat are presented. Using an
      attenuated total reflection (ATR) infrared cell, a novel Fourier transform
      infrared (FTIR) spectroscopic method that was developed for the rapid (5 min)
      quantitation of the total trans fatty acid levels in neat (without solvent) fats
      and oils measured as triacylglycerols (TAG) is discussed. TAG required no
      derivatization, but had to be melted prior to measurement. The lower limit of
      trans quantitation was 5% of total fat. The precision of this ATR method was
      found to be superior to that of transmission infrared official methods. Accuracy
      was enhanced by generating a symmetric absorption trans infrared band at 966 cm(
      1) on a horizontal background. This was achieved by "ratioing" the single-beam
      spectrum of the trans-containing fat or oil against that of a reference oil or
      standard having only cis double bonds. Attempts to apply this ATR-FTIR method to
      food matrixes with low trans fat and/or low total fat content were not
      satisfactory due to interfering infrared absorptions in the trans region. To
      overcome this interference, the method was modified by applying the standard
      addition technique to the ATR-FTIR determination. The modified procedure required
      more time, but eliminated any adverse impact on accuracy arising from interfering
      minor food components having absorption bands near 966 cm(-1).

PMID- 15164854
TI  - Improved identification of conjugated linoleic acid isomers using silver-ion HPLC
      separations.
AB  - Silver-ion high-performance liquid chromatography (Ag+-HPLC) has been shown to be
      effective in the resolution of most of the isomers of conjugated octadecadienoic
      acids (18:2), also known as conjugated linoleic acid (CLA). The CLA isomers
      identified in natural fats from ruminants are a mixture of numerous positional
      and geometric isomers from 7,9- to 12,14-18:2. Ag+-HPLC separates both geometric
      (trans,trans < cis/trans < cis,cis) and positional CLA isomers using the mobile
      phase hexane/acetonitrile (99.9:0.1). The elution volumes for the CLA isomers
      were not only affected by the concentration of acetonitrile (in the prepared
      mobile phase) but also with successive runs during the day using a prepared
      mobile phase batch, due to the partial solubility of acetonitrile in hexane.
      However, this drift does not affect the relative resolution of the CLA isomers.
      The addition of diethyl ether to the mobile phase partly stabilizes the solvent
      mixture. In order to facilitate the interpretation of Ag-+HPLC chromatograms, the
      relative retention volumes (RRV) were calculated for each CLA isomer. Toluene was
      added to all the test portions and served as an estimator of dead volume, whereas
      the elution of the ubiquitous 9c,11t-CLA isomer was chosen as unity (1.00).
      Expressing the elution of all the CLA isomers as their RRV greatly helped to
      standardize each CLA isomer, resulting in relatively small coefficients of
      variation (% CV) for the trans,trans (<1.5%) and cis/trans (<0.5%) CLA isomers.
      The identification of the CLA isomers was further facilitated by synthesis of
      authentic CLA isomers. All the geometric CLA fatty acid methyl esters (FAME) from
      positions 6,8- to 13,15-CLA were commercially available or synthesized by a
      combination of partial hydrazine reduction of known polyunsaturated fatty acids
      followed by alkali isomerization, isolation of products, and further iodine
      catalyzed geometric isomerization. Based on expressing the elution volume as RRV
      and the availability of the synthetic CLA isomers, a unique reversal of the
      elution order of the c/t CLA isomers was found. It is also proposed that the
      retention times of CLA isomers by gas chromatography (GC) should be expressed as
      their relative retention times (RRT) relative to methyl gamma-linoleneate. The
      availability of CLA reference materials and the application of RRV and RRT to Ag+
      HPLC and GC separations, respectively, will greatly improve in the
      identifications of CLA isomers.

PMID- 15164853
TI  - Methods for analysis of conjugated linoleic acids and trans-18:1 isomers in dairy
      fats by using a combination of gas chromatography, silver-ion thin-layer
      chromatography/gas chromatography, and silver-ion liquid chromatography.
AB  - Conjugated linoleic acids (CLA) are octadecadienoic acids (18:2) that have a
      conjugated double-bond system. Interest in these compounds has expanded since CLA
      were found to be associated with a number of physiological and pathological
      responses such as cancer, metastases, atherosclerosis, diabetes, immunity, and
      body fat/protein composition. The main sources of these conjugated fatty acids
      are dairy fats. Rumen bacteria convert polyunsaturated fatty acids, especially
      linoleic and linolenic acids, to CLA and numerous trans- containing mono- and
      diunsaturated fatty acids. It has been established that an additional route of
      CLA synthesis in ruminants and monogastric animals, including humans, occurs via
      delta9 desaturation of the trans-18:1 isomers. To date, a total of 6 positional
      CLA isomers have been found in dairy fats, each occurring in 4 geometric forms
      (cis,trans; trans,cis; cis,cis; and trans,trans) for a total of 24. All of these
      CLA isomers can be resolved only by a combination of gas chromatography (GC),
      using 100 m highly polar capillary columns, and silver-ion liquid chromatography,
      using 3 of these 25 cm columns in series. Complete analysis of all the trans-18:1
      isomers requires prior isolation of trans monoenes by silver-ion thin-layer
      chromatography (TLC), followed by GC analysis using the same 100 m capillary
      columns operated at low temperatures starting from 120 degrees C. These
      analytical techniques are required to assess the purity of commercial CLA
      preparations, because their purity will affect the interpretation of any
      physiological and/or biochemical response obtained. Prior assessment of CLA
      preparations by TLC is also recommended to determine the presence of any other
      impurities. The availability of pure CLA isomers will permit the evaluation and
      analysis of individual CLA isomers for their nutritional and biological activity
      in model systems, animals, and humans. These techniques are also essential to
      evaluate dairy fats for their content of specific CLA isomers and to help design
      experimental diets to increase the level of the desired CLA isomers in dairy
      fats. These improved techniques are further required to evaluate the CLA profile
      in monogastric animals fed commercial CLA preparations for CLA enrichment of
      animal products. This is particularly important because absorption and metabolism
      will alter the ingested-CLA profile in the animal fed.

PMID- 15164855
TI  - Exploring the association between anxiety and conduct problems in a large sample
      of twins aged 2-4.
AB  - Anxiety and conduct problems covary, yet studies have not explored the genetic
      and environmental origins of this association. We analyzed parent-reported
      anxiety and conduct problems in 6,783 pairs of twins at 2-, 3-, and 4-years of
      age. As anxiety and conduct problems were fairly stable across the three ages
      (average 1-year correlation was .53), ratings from all three were combined. The
      aggregate anxiety and conduct ratings correlated .33 for boys and .30 for girls.
      Bivariate genetic analyses indicated fairly low genetic correlations (.31 for
      boys, .16 for girls), and high shared environmental correlations (1.0 for boys
      and 0.99 for girls) between anxiety and conduct problems. Most of the phenotypic
      correlation was accounted for by shared environmental mediation (65% for boys and
      94% for girls), indicating that many of the same family environmental factors are
      responsible for the development of both anxiety and conduct problems.

PMID- 15164856
TI  - Child maltreatment and emergent personality organization: perspectives from the
      five-factor model.
AB  - The Five-Factor Model was used to examine personality organization in 211 six
      year-old children (135 maltreated and 76 nonmaltreated). Longitudinal assessments
      were conducted at ages 7, 8, and 9. Six-year-old maltreated children exhibited
      lower agreeableness, conscientiousness, and openness to experience and higher
      neuroticism than did nonmaltreated children. Maltreated children also were more
      frequently represented in less adaptive personality clusters than were their
      nonmaltreated counterparts. A particularly vulnerable profile occurred
      predominantly among maltreated children and was related to experiencing both
      abuse and neglect. Child maltreatment and personality clusters were related to
      individual differences perceived by peers. Longitudinal stability of the
      personality dimensions also was assessed. At age nine, evidence was found for
      maintenance of the organization of the personality clusters obtained at age six
      and for continuity of maltreated children's personality liabilities.

PMID- 15164857
TI  - Cognitive moderators of the longitudinal association between peer rejection and
      adolescent depressive symptoms.
AB  - This longitudinal study examined peer rejection as a predictor of adolescent
      depressive symptoms during the critical developmental period associated with
      substantial increases in the prevalence of girls' depression. In a sample of 158
      adolescents aged 15-17 years, a peer nomination, sociometric assessment was
      conducted to examine adolescents' peer status at an initial time point, along
      with self-report measures of depressive symptoms, depressogenic attributions, and
      peer importance. Adolescents completed a second measure of depressive symptoms 17
      months later. Results were consistent with integrated cognitive vulnerability
      stress and cognitive dissonance models, particularly for girls. Specifically,
      peer rejection was a significant prospective predictor of depressive symptoms
      when combined with high levels of importance ascribed to peer status and high
      levels of adolescents' depressogenic attributional styles.

PMID- 15164858
TI  - Negative affect in victimized children: the roles of social withdrawal, peer
      rejection, and attitudes toward bullying.
AB  - This study evaluated the validity of mediating pathways in predicting self
      assessed negative affect from shyness/social withdrawal, peer rejection,
      victimization by peers (overt and relational), and the attitude that aggression
      is legitimate and warranted. Participants were 296 3rd through 5th graders (156
      girls, 140 boys) from 10 elementary schools. Self-report measures of
      victimization, attitudes, and negative affect, and a teacher-report measure of
      shyness/social withdrawal and peer rejection were completed during the spring
      semesters of 2 consecutive years. Hierarchical regression analyses supported the
      mediational model in predicting negative affect at Time 2. However, an increase
      in negative affect over the 12-month study period was best accounted for by
      direct effects of increased victimization and changes in attitudes/attributions
      regarding aggression. Implications for the planning of school interventions
      designed to interrupt these victimization-maladjustment pathways are discussed.

PMID- 15164859
TI  - Risk as a moderator of the effects of prevention programs for children from
      divorced families: a six-year longitudinal study.
AB  - Program by risk interactions were assessed to evaluate whether the long-term
      effects of two preventive interventions for children from divorced families were
      moderated by baseline levels of risk. Six-year prospective relations between
      childhood (ages 9-12) and adolescence (ages 15-19) were examined in 68 children
      who comprised the control group of a randomized trial. Analyses indicated that
      two childhood variables predicted multiple adolescent outcomes: environmental
      stressors and externalizing problems. A risk index composed of these 2 variables
      was highly predictive of internalizing and externalizing problems, competence,
      substance use, and mental disorder 6 years later. Analyses of the full sample (N
      = 218) indicated that program effects were greater for children with higher risk
      scores and that the programs attenuated the relation between risk and adolescent
      internalizing and externalizing problems, competence, and mental disorder.

PMID- 15164860
TI  - Everyday marital conflict and child aggression.
AB  - Children's immediate aggressive responding to exposure to marital conflict was
      examined. Participants were 108 families with 8- to 16-year-old children (53
      boys, 55 girls), with diary records of children's reactions to marital conflict
      in the home completed by 103 mothers (n = 578 records) and 95 fathers (n = 377
      records) during a 15-day period. Child responses to analog presentations of
      marital conflict tactics were also obtained. Exposure to destructive conflict
      tactics and negative parental emotionality increased the likelihood of aggressive
      behavior in children when they witnessed marital conflict, whereas constructive
      conflict tactics and positive parental emotionality decreased the probability of
      aggression. Conflict topics presumed to be threatening to the child (child- or
      marital-related) also heightened the likelihood of aggression. Aggressive
      responding to conflict in both home and laboratory predicted externalizing
      behavior problems. Fathers' and mothers' separate diary reports, and child
      responses to analog presentation of conflict, provided generally consistent
      findings. An exposure hypothesis for marital conflict as an influence on child
      aggression is discussed.

PMID- 15164861
TI  - Parenting disruptive preschoolers: experiences of mothers and fathers.
AB  - This study examined parental functioning and interactions with young children
      with Oppositional Defiant Disorder (ODD), with emphasis on differences between
      mothers and fathers in their responses to their child and in their unique
      contributions to the prediction of child disruptive behavior. Participants were
      53 3- to 6-year olds with ODD who presented for treatment with two parents.
      Mothers reported more severe disruptive behavior and higher parenting stress than
      fathers. During parent-child interactions, mothers showed more responsiveness
      than fathers, even though children were more compliant during interactions with
      fathers. Regression analyses showed that fathers' parent-related stress was
      predictive of both mothers' and father's reports of disruptive child behavior;
      mothers' marital satisfaction was predictive of behavioral observations of child
      compliance with both mothers and fathers. This study revealed several important
      differences in the experiences of mothers versus fathers of disruptive children
      and indicates the importance of including the father in the child's assessment
      and treatment.

PMID- 15164862
TI  - Gender differences in the effects of oppositional behavior on teacher ratings of
      ADHD symptoms.
AB  - H. Abikoff, M. Courtney, W. E. Pelham, and H. S. Koplewicz (1993) presented
      elementary school teachers with a videotape of a 4th-grade male child exhibiting
      behavior associated with either Attention Deficit Hyperactivity Disorder (ADHD)
      or Oppositional Defiant Disorder (ODD). Comparisons with ratings generated from a
      control tape (same child exhibiting unremarkable behavior) suggested that
      oppositional tendencies inflated teacher ratings of ADHD for boys. The term "halo
      effect" has been used in the literature to refer to the impact of one class of
      behavior on the perception of another. This study replicated this procedure using
      identical scripts with both male and female child models. Oppositional behavior
      was associated with higher teacher ratings of hyperactivity and inattentiveness.
      Portrayals of behavior associated with ADHD generated higher teacher ratings of
      oppositional conduct. This bidirectional effect differed in magnitude as a
      function of child gender. The boy actor exhibiting oppositional behavior received
      teacher ratings of hyperactivity and inattention that were roughly half of those
      elicited by his portrayal of ADHD itself. The girl actor portraying ADHD
      generated oppositional defiant ratings that were roughly two thirds of those
      elicited from her performance as a child with ODD. These teacher rating
      tendencies could contribute to higher diagnostic rates of ADHD among boys and ODD
      among girls. Available epidemiologic data indicate a much higher rate of ADHD
      among boys and prevalence differentials for ODD (girls initially lower) that
      disappear by adolescence. Future research will be required to determine the
      extent to which these teacher response sets generalize to other evaluators such
      as parents, physicians and mental health professionals.

PMID- 15164864
TI  - Implementation of Hawaii's Prepaid Health Care Act: root cause of a health care
      monopoly.

PMID- 15164863
TI  - Association of normative beliefs and anger with aggression and antisocial
      behavior in Russian male juvenile offenders and high school students.
AB  - Examined the association of anger experience and two types of normative beliefs
      with physical aggression and nonaggressive antisocial behavior in 361 juvenile
      offenders and 206 high school students in Russia. All participants were male and
      ranged in age from 14 to 18 years. Higher frequency of aggressive acts was
      significantly associated with higher levels of anger and stronger beliefs that
      physical aggression is an appropriate course of action in conflicts. After
      statistically controlling for nonaggressive antisocial behavior, the relationship
      between physical aggression and antisocial beliefs was not significant.
      Similarly, with physical aggression controlled, nonaggressive antisocial behavior
      was uniquely associated with approval of deviancy, but not with anger or beliefs
      legitimizing aggression. Juvenile offenders reported higher levels of anger
      experience and higher frequency of aggression and antisocial behavior compared to
      high school students. There were no differences in normative beliefs between
      these two groups. This specificity of association of social-cognitive and emotion
      regulation processes to aggressive and nonaggressive forms of antisocial behavior
      may be relevant to understanding the mechanisms of cognitive-behavioral therapy
      for conduct disorder and antisocial behavior.

PMID- 15164865
TI  - A community-based asthma management program: effects on resource utilization and
      quality of life.
AB  - OBJECTIVE: The Waianae Coast Comprehensive Health Center (WCCHC) developed an
      integrated community-based asthma management program in an effort to reduce
      inappropriate medical utilization and improve quality of life in their pediatric
      asthma population. METHODS: Over a period of three years, eighty-eight children
      with asthma participated in the community-based asthma management program. During
      this time, an automated asthma tracking system was developed, the WCCHC
      established a standard system of care based on the National Asthma Education and
      Prevention Program Expert Panel Report Guidelines for the Diagnosis and
      Management of Asthma (NAEPP Asthma Guidelines) adapted for cultural sensitivity,
      and a coordinated team care approach was implemented in the asthma management
      program. RESULTS: During the pilot study, forty children participated in the
      program. Among these forty individuals, there was a significant decrease in both
      per capita expenditures and asthma related visits after community health worker
      (CHW) intervention. Average per capita charges decreased from dollar 735 to
      dollar 181, Emergency Department (ED) visits decreased from 60 to 10, and the
      overall asthma related visits decreased from 1.5 to 0.25 per person after the
      initial CHW encounter. These results were replicated during the 2000-2001
      intervention period where average per capita charges decreased from dollar 310 to
      dollar 129 and ED encounters dropped from 32 to 10 after the first CHW encounter.
      In addition, the number of high utilizers-defined as those presenting to the ED
      two or more times for asthma-related diagnoses- sharply decreased from 176 in
      1998 to only 16 in 2001. Quality of life improved, with 72% fewer nighttime and
      96% fewer daytime symptoms reported after CHW intervention during the pilot
      study. During the year 2000, symptoms during exercise and asthma related doctor
      visits decreased 59% and 67% respectively after CHW intervention. CONCLUSION: The
      community-based asthma management program demonstrated success in improving
      utilization patterns and reducing asthma-related expense among program
      participants. Improvement was also noted in quality of life as expressed through
      frequency and time of asthma symptoms. Other health care institutions may also be
      positively impacted by developing multidisciplinary team implemented, culturally
      adapted, and scientifically-based disease management programs.

PMID- 15164867
TI  - Surgical notes from ancient Tonga.

PMID- 15164866
TI  - Occurrence of neural tube defects and Down syndrome among siblings.
AB  - A recent study had reported increased risk of Down syndrome among siblings of
      Infants with neural tube defects (NTDs) and vice versa. However Hawaii Birth
      Defects Registry data indicate no elevated risk of Down syndrome among older
      siblings of infants with NTDs and vice versa, contradicting the findings of the
      previous study. Further investigation of the potential relationship is warranted.

PMID- 15164868
TI  - Laboratory professionals: the "behind the scene" partner in healthcare.

PMID- 15164869
TI  - Oncology nurses ... who are we?
AB  - Oncology nursing has matured into a well-established specialty in nursing. The
      scope of practice for the oncology nurse is broad and spans the continuum of
      cancer care. Oncology nurses have important roles in all aspects of cancer care.
      The ONS is the largest organization of oncology professionals in the United
      States with a membership of about 30,000 and has contributed to the development
      of oncology nursing through its many educational programs, support of research,
      opportunities for networking, establishment of certification examinations, and
      development of an active foundation.

PMID- 15164870
TI  - Biology of the epidermal growth factor receptor family.

PMID- 15164871
TI  - Integrin signaling in cancer.

PMID- 15164872
TI  - Regulators of vascular endothelial growth factor expression in cancer.

PMID- 15164873
TI  - Integrin-linked kinase (ILK) in combination molecular targeting.

PMID- 15164874
TI  - p21-activated kinase 1: an emerging therapeutic target.

PMID- 15164875
TI  - Basis and importance of Src as a target in cancer.

PMID- 15164876
TI  - Therapeutic targeting of the receptor tyrosine kinase Met.

PMID- 15164877
TI  - Nuclear factor-kappaB activation mediates cellular transformation, proliferation,
      invasion angiogenesis and metastasis of cancer.

PMID- 15164878
TI  - The p53 pathway: targets for the development of novel cancer therapeutics.

PMID- 15164879
TI  - Runx protein signaling in human cancers.

PMID- 15164880
TI  - Signal transduction mediated by cyclin D1: from mitogens to cell proliferation: a
      molecular target with therapeutic potential.

PMID- 15164881
TI  - Signal transduction pathways in Bcr-Abl transformed cells.

PMID- 15164882
TI  - Estrogen receptors and anti-estrogen therapies.

PMID- 15164883
TI  - Targeting endothelin axis in cancer.

PMID- 15164884
TI  - km23: a novel TGFbeta signaling target altered in ovarian cancer.

PMID- 15164885
TI  - How much do crashes related to obstructive sleep apnea cost?

PMID- 15164886
TI  - Work hours and sleep in residency training.

PMID- 15164887
TI  - Low-dose repeated caffeine administration for circadian-phase-dependent
      performance degradation during extended wakefulness.
AB  - OBJECTIVE: To investigate whether the effectiveness of a novel high-frequency low
      dose caffeine regimen in counteracting the deterioration of performance during
      extended wakefulness is related to its interaction with homeostatic or circadian
      signals modulating performance and sleep propensity. DESIGN: Double-blind,
      placebo-controlled, parallel-group design in a 29-day forced desynchrony paradigm
      in which the period of the sleep-wake cycle was scheduled to be 42.85 hours,
      i.e., far removed from the circadian range. This design allowed for separate
      estimation of the sleep homeostatic, circadian, and caffeine contributions to
      performance deficits or improvements. SETTING: Private suite of a general
      clinical research center, in the absence of time of day information.
      PARTICIPANTS: Sixteen healthy normal-sleeping men (aged 18-30 years)
      INTERVENTIONS: Caffeine (0.3 mg per kg per hour) or placebo was administered
      hourly during the 28.57-hour wake episodes. RESULTS: Plasma caffeine
      concentrations rose in an exponential saturating manner during wakefulness.
      Rising caffeine levels markedly attenuated wake-dependent deterioration of a
      number of measures of cognitive performance, particularly at the circadian
      performance nadir. Moreover, caffeine enhanced the ability of subjects to remain
      consistently awake for extended periods, holding subjects back from completing
      the full transition to sleep, but at the expense of increasing subjective
      sleepiness. CONCLUSIONS: High-frequency low-dose caffeine administration is
      effective in countering the detrimental performance effects of extended
      wakefulness. These data are in accordance with the hypothesis that adenosine is a
      mediator of performance decrements associated with extended wakefulness and may
      lead to new strategies to use caffeine in situations in which neurobehavioral
      functioning is affected by sleep loss.

PMID- 15164889
TI  - Murine Multiple Sleep Latency Test: phenotyping sleep propensity in mice.
AB  - STUDY OBJECTIVES: Objectives were to (1) establish a measure of sleep propensity
      for a more comprehensive characterization of sleepiness in murine genetics and
      interventional studies and (2) to characterize sample sizes necessary for
      statistical differences in effect. DESIGN: Average multiple sleep latency values
      were compared in mice, varying strain, circadian time, and forced-wakefulness
      conditions. SUBJECTS: Adult male mice of inbred strains were studied.
      INTERVENTIONS: Mice were implanted with electroencephalographic and
      electromyographic recording electrodes. Twenty-four-hour periods of stable
      baseline sleep activity (> 600 minutes) were confirmed prior to baseline sleep
      latency testing. Average sleep latencies were obtained across 10- and 20-minute
      nap opportunities within 4 consecutive 30-minute periods. Forced wakefulness
      protocols were performed prior to additional sleep-latency tests. MEASUREMENTS
      AND RESULTS: Sleep-latency testing with 20-minute nap opportunities every 30
      minutes revealed a shorter sleep latency in the lights-on period (12.4 minutes +/
      0.9 vs 16.5 +/- 1, P < .001), a substantial reduction in sleep latencies in mice
      subjected to 6-hour forced wakefulness (eg, C57BL/6J baseline: 12.4 +/- 0.9
      minutes, and forced wakefulness, 8.5 +/- 0.9 minutes, P < .01), and strain
      differences in latencies following short-term forced wakefulness (P < .01).
      Sample sizes for 85% power to detect a 25% reduction in the 20-minute daytime
      Murine Multiple Sleep Latency Test require fewer than 20 mice per group for
      commonly used transgenic background strains. CONCLUSIONS: The Murine Multiple
      Sleep Latency Test is a robust measure of sleep propensity, and the latency
      varies with homeostatic and circadian influences. The test requires minimal added
      time to standard murine sleep recordings, yet yields important additive
      information.

PMID- 15164888
TI  - Pontine intertrigeminal region attenuates sleep apneas in rats.
AB  - STUDY OBJECTIVES: To determine whether the pontine intertrigeminal region (ITR),
      with recently described anatomic connections and an effect on vagally induced
      reflex apnea, has an impact on spontaneous sleep apneas in rats. DESIGN:
      Respiration, electroencephalogram (EEG), and electromyogram (EMG) were recorded
      in rats with lesions of the pontine ITR and in control animals. PARTICIPANTS: 9
      adult male Sprague-Dawley rats. INTERVENTIONS: Rats were implanted with EEG and
      EMG electrodes and were polygraphically recorded for 6 hours, and their
      respiration was monitored by placing each animal inside a single-chamber
      plethysmograph. Subsequently, a respiratory-related intertrigeminal site was
      identified by probing on dorsoventral tracks with 2 to 5 nL glutamate (10 nL, 10
      mmol) injections from a multibarrel glass pipette. This site was then lesioned by
      injecting ibotenic acid (10 nL, 50 mmol) from a second pipette barrel. Animals
      were again recorded for 6 hours on days 2, 7, and 14 after the lesion.
      MEASUREMENTS AND RESULTS: ITR lesions exerted no impact on mean respiratory
      pattern during any sleep-wake state, compared to baseline recordings. In
      contrast, apnea frequency during non-rapid eye movement sleep increased following
      ITR lesion, more than doubling by day 14. CONCLUSIONS: This study demonstrates
      that a small and well-localized unilateral lesion of the ITR region in the
      lateral pons can increase sleep apnea expression in freely moving rats over a 2
      week period. The present findings are in agreement with the general modulatory
      role of pontine structures in activities including respiration, heart rate, and
      regulation of blood pressure.

PMID- 15164890
TI  - Consolidation of strictly episodic memories mainly requires rapid eye movement
      sleep.
AB  - STUDY OBJECTIVES: The aim of this study is to examine the effects of sleep
      deprivation during the first or second half of the night on episodic memory
      consolidation. Episodic memory is defined as memory for events located in time
      and space. It is also characterized by autonoetic consciousness, which gives a
      subject the conscious sensation of traveling back in time to relive the original
      event and forward into the future. DESIGN: Consolidation of episodic information
      was tested after 4-hour retention intervals, which followed learning and occurred
      during either the early or late half night, respectively dominated by slow wave
      sleep (SWS) or rapid eye movement (REM) sleep, or corresponding periods of
      wakefulness. SETTING: Data collection occurred in the sleep laboratory.
      PARTICIPANTS: Forty-three young healthy subjects: 9 men and 34 women, age ranging
      from 18 to 26 years (mean 20.18 +/- 1.94 years) were included in this study.
      INTERVENTIONS: Waking after a 4-hour retention interval filled with early or late
      sleep, or 4-hour sleep deprivation, during early or late period of night.
      MEASUREMENTS AND RESULTS: The cognitive task, named the What-Where-When test, was
      specially designed to assess factual, spatial, and temporal components of
      episodic memory. This task was associated with the Remember/Know paradigm to
      assess autonoetic consciousness. We measured performance on immediate free
      recall, delayed free recall (after a 4-hour interval of wakefulness or sleep),
      and delayed recognition. We also calculated a forgetting rate for each feature
      (factual, spatial, and temporal) and, for the recognition task, scores of
      autonoetic consciousness (R responses). REM-sleep deprivation was associated with
      significantly lower recall of spatial information compared to SWS deprivation (P
      < .01) or late sleep (P < .05) conditions. REM-sleep deprivation was also
      associated with a higher forgetting rate of temporal information as compared to
      the early sleep condition (P< .01). Finally, REM-sleep deprivation led subjects
      to give significantly fewer R responses, indicative of true memories, as compared
      to SWS deprivation (P < .05). CONCLUSIONS: These results suggest that
      consolidation of truly episodic memories mainly involves REM sleep.

PMID- 15164891
TI  - Minimal olfactory perception during sleep: why odor alarms will not work for
      humans.
AB  - STUDY OBJECTIVES: To examine olfactory arousal threshold during sleep in
      comparison to an auditory tone. DESIGN: On night 1, participants rated odor
      intensity when awake and experienced olfactory stimuli during stage 1 sleep.
      Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials
      using the "staircase" threshold-detection method. Electroencephalogram,
      electrooculogram, electromyogram, electrocardiogram, and respiration were
      recorded along with behavioral response. An 800-Hz tone was given on trials when
      odors failed to arouse. SETTING: Participants slept in individual rooms. Stimulus
      delivery systems were operated from a separate room, where an experimenter
      observed physiologic recordings and behavioral responses. PARTICIPANTS: Three
      healthy men and 3 women aged 20 to 25 years (mean, 22 years). INTERVENTIONS: Two
      odorants, peppermint and pyridine, at 4 concentrations were presented through
      nasal cannulas using an air-dilution olfactometer. Tones were played over a
      speaker. MEASUREMENTS: Behavioral (button press and oral) responses,
      electroencephalographic activation, and changes in breathing and heart rate were
      assessed. RESULTS: Participants responded to odors on 92% of stage 1 sleep
      trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine
      produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one
      third of REM sleep trials. Tones were effective on at least 75% of trials. Heart
      rate increased significantly only following behavioral responses to odors or
      tones across sleep stages. CONCLUSIONS: The data indicate that human olfaction is
      not reliably capable of alerting a sleeper.

PMID- 15164892
TI  - Changes in sleep patterns in spontaneously hypertensive rats.
AB  - STUDY OBJECTIVES: To explore whether spontaneous hypertension is associated with
      a change in sleep pattern in rats. DESIGN: Adult male spontaneously hypertensive
      rats (SHR) were compared to normotensive Wistar-Kyoto rats (WKY) on their normal
      daytime sleep pattern. PARTICIPANTS: Ten WKY and 10 SHR. INTERVENTIONS: All rats
      had electrodes implanted for polygraphic recordings. Weeks later, a 5-hour
      daytime sleep-weakfulness recording session was analyzed. MEASUREMENTS AND
      RESULTS: Electroencephalogram and electromyogram signals were subjected to
      continuous power spectral analysis, from which mean power frequency of the
      electroencephalogram and power of the electromyogram were quantified. Active
      waking (AW), quiet sleep (QS), and paradoxical sleep (PS) were defined every 8
      seconds from corresponding mean power frequency and electromyogram power
      readings. Analysis of heart-rate variability was derived from the
      electrocardiogram signals. Macrostructural analysis of sleep revealed that SHR
      were characterized by fewer QS and PS episodes and eventually shorter accumulated
      QS and PS times as compared to WKY. SHR also had more QS-to-AW transitions but
      fewer QS-to-PS transitions. Microstructural analysis revealed that SHR were
      associated with more-frequent interruptions during QS. Analysis of heart-rate
      variability indicated that SHR had similar R-R intervals and lower high-frequency
      (0.6-2.4 Hz) power but a higher ratio of low-frequency (0.06-0.6 Hz) power to
      high-frequency power during the daytime recording as compared to WKY.
      CONCLUSIONS: As compared to WKY, SHR may have less sleep time, poorer sleep
      quality, and a greater tendency to wake up from QS. Such changes in sleep may be
      concomitant with cardiac autonomic changes. Our methodology offers a convenient
      yet effective way to study the constitution, sequence, and interruption of sleep
      in the rat.

PMID- 15164893
TI  - Association between delayed sleep phase and hypernyctohemeral syndromes: a case
      study.
AB  - STUDY OBJECTIVE: We investigated whether the hypernyctohemeral syndrome (non-24
      hour sleep-wake syndrome) may show a clinical association with the delayed sleep
      phase syndrome (DSPS) in a 39-year-old woman who developed sleep disturbances
      following a traumatic brain injury. MEASUREMENTS AND RESULTS: Sleep-wake log
      documentation and wrist-activity recordings for more than 6 consecutive months
      confirmed the patient's tendency to live on longer-than-24-hour "days." Episodes
      of relative coordination to the 24-hour day were also noted, suggesting that the
      patient was transiently in and out of phase with environmental synchronizers too
      weak to fully entrain her to the geophysical environment. Interestingly, we noted
      a tendency to initiate sleep between 3:00 am and 5:00 am and wake up from sleep
      between noon and 1:00 pm. CONCLUSIONS: These results support an association
      between the hypernyctohemeral syndrome and the DSPS. This association may carry
      implications for the treatment of circadian rhythms disorders.

PMID- 15164894
TI  - Systematic interindividual differences in neurobehavioral impairment from sleep
      loss: evidence of trait-like differential vulnerability.
AB  - OBJECTIVES: To investigate interindividual differences in neurobehavioral
      deficits during sleep deprivation, and to establish to what extent the
      neurobehavioral responses to sleep loss are a function of sleep history versus
      trait-like differential vulnerability. DESIGN: Individuals were exposed to sleep
      deprivation on 3 separate occasions in order to determine the stability of
      interindividual differences in neurobehavioral impairment. SETTING: The sleep
      deprivation experiments were conducted under standardized laboratory conditions
      with continuous monitoring of wakefulness. Each subject underwent a laboratory
      adaptation session before entering the sleep-deprivation phase of the study.
      PARTICIPANTS: A total of 21 healthy adults (aged 21-38 years) completed the
      experiment. INTERVENTIONS: Subjects came to the laboratory 3 times at intervals
      of at least 2 weeks. During each laboratory session, they underwent
      neurobehavioral testing every 2 hours during 36 hours of total sleep deprivation,
      which was preceded by baseline sleep and followed by recovery sleep. In the week
      prior to each sleep-deprivation session and on the baseline night in the
      laboratory, subjects were required to either restrict their sleep to 6 hours per
      day (prior sleep restriction condition) or to extend their time in bed to 12
      hours per day (prior sleep extension condition), so as to experimentally
      manipulate sleep history (in randomized counterbalanced order). RESULTS: There
      was strong evidence that interindividual differences in neurobehavioral deficits
      during sleep deprivation were systematic and trait-like. The magnitude of
      interindividual variability was substantial relative to the magnitude of the
      effect of prior sleep restriction (which on average involved a reduction of 4.1
      hours sleep per day, compared to prior sleep extension, for 7 days). Overall,
      interindividual differences were not explained by subjects' baseline functioning
      or a variety of other potential predictors. Interindividual variability clustered
      on 3 distinct neurobehavioral dimensions: self-evaluation of sleepiness, fatigue,
      and mood; cognitive processing capability; and behavioral alertness as measured
      by sustained attention performance. CONCLUSIONS: Neurobehavioral deficits from
      sleep loss varied significantly among individuals and were stable within
      individuals. Interindividual differences in neurobehavioral responses to sleep
      deprivation were not merely a consequence of variations in sleep history. Rather,
      they involved trait-like differential vulnerability to impairment from sleep
      loss, for which neurobiologic correlates have yet to be discovered.

PMID- 15164895
TI  - Modafinil improves alertness, vigilance, and executive function during simulated
      night shifts.
AB  - STUDY OBJECTIVES: To assess the effect of 200 mg of modafinil compared to placebo
      on alertness, neurobehavioral performance, and executive function during 4
      consecutive simulated night shifts. DESIGN: Double-blind, randomized, parallel
      groups. SETTING: Sleep research facility. PARTICIPANTS: 32 male and female
      volunteers between the ages of 18 and 55 years. INTERVENTIONS: 200 mg of
      modafinil or placebo given nightly on the 4 consecutive simulated night shifts.
      MEASUREMENTS AND RESULTS: Subjects were randomly assigned to 1 of the 2 treatment
      conditions, following medical, psychiatric, and polysomnographic screening. On 4
      consecutive nights, subjects took study drug at 2200, and then from about 2300 to
      0730 participated in a simulated night shift that included the Maintenance of
      Wakefulness Test, Psychomotor Vigilance Test, Digit Symbol Substitution Test,
      measures of subjective alertness, and multiple executive-function measures. At
      0800, daytime sleep periods were recorded polysomnographically for 6 to 8 hours.
      Alertness--as measured by the MWT, vigilance and reaction time as indexed by
      Psychomotor Vigilance Test lapses, and slowest 10% of reaction times--and 3
      executive-function tasks showed significant enhancement with modafinil versus
      placebo. Subjective sleepiness at night and some performance measures did not
      show consistent treatment differences. Daytime sleep showed minimal differences
      between conditions. CONCLUSIONS: The physiologic sleepiness and neurobehavioral
      deficits that occurred during the hours of a typical night shift were clearly
      attenuated by modafinil. Modafinil also had beneficial effects on some measures
      of executive function.

PMID- 15164896
TI  - A prospective study of sleep duration and mortality risk in women.
AB  - STUDY OBJECTIVES: It is commonly believed that 8 hours of sleep per night is
      optimal for good health. However, recent studies suggest the risk of death is
      lower in those sleeping 7 hours. We prospectively examined the association
      between sleep duration and mortality in women to better understand the effect of
      sleep duration on health. DESIGN: Prospective observational study. SETTING:
      Community-based. PARTICIPANTS: Women in the Nurses Health Study who answered a
      mailed questionnaire asking about sleep duration in 1986. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Vital status was ascertained through questionnaires,
      contact with next of kin, and the National Death Index. During the 14 years of
      this study (1986-2000), 5409 deaths occurred in the 82,969 women who responded to
      the initial questionnaire. Mortality risk was lowest among nurses reporting 7
      hours of sleep per night. After adjusting for age, smoking, alcohol, exercise,
      depression, snoring, obesity, and history of cancer and cardiovascular disease,
      sleeping less than 6 hours or more than 7 hours remained associated with an
      increased risk of death. The relative mortality risk for sleeping 5 hours or less
      was 1.15 (95% confidence interval [CI], 1.02-1.29) for 6 hours, 1.01 (95% CI,
      0.94-1.08), for 7 hours, 1.00 (reference group), for 8 hours, 1.12 (95% CI, 1.05
      1.20), and for 9 or more hours 1.42 (95% CI, 1.27-1.58). CONCLUSIONS: These
      results confirm previous findings that mortality risk in women is lowest among
      those sleeping 6 to 7 hours. Further research is needed to understand the
      mechanisms by which short and long sleep times can affect health.

PMID- 15164897
TI  - Increasing task difficulty facilitates the cerebral compensatory response to
      total sleep deprivation.
AB  - STUDY OBJECTIVES: To test the role of task difficulty in the cerebral
      compensatory response after total sleep deprivation (TSD). DESIGN: Subjects
      performed a modified version of Baddeley's logical reasoning task while
      undergoing functional magnetic resonance imaging twice: once after normal sleep
      and once following 35 hours of TSD. The task was modified to parametrically
      manipulate task difficulty. SETTING: Inpatient General Clinical Research Center
      and outpatient functional magnetic resonance imaging center. PATIENTS OR
      PARTICIPANTS: 16 young adults (7 women; mean age, 27.6 +/- 6.1 years; education,
      15.4 +/- 1.8 years) were included in the final analyses. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Behaviorally, subjects performed the same after TSD as
      while well rested. Neuroimaging data revealed a linear increase in cerebral
      response with a linear increase in task demands in several brain regions after
      normal sleep. Even stronger linear responses were found after TSD in several
      brain regions, including bilateral inferior parietal lobes, bilateral temporal
      cortex, and left inferior and dorsolateral prefrontal cortex. CONCLUSIONS: Task
      difficulty facilitates the cerebral compensatory response observed following TSD.
      Compensation manifests as both new regions that did not show significant
      responses to task demands in the well-rested condition, as well as stronger
      responses within regions typically underlying task performance. The possible
      significance of these 2 types of responses should be explored further, as should
      the importance of the parietal lobes for cognitive performance after TSD.

PMID- 15164898
TI  - Reducing motor-vehicle collisions, costs, and fatalities by treating obstructive
      sleep apnea syndrome.
AB  - STUDY OBJECTIVES: Drivers suffering from obstructive sleep apnea syndrome (OSAS)
      have an increased risk for being involved in motor-vehicle collisions. This study
      estimates, for the first time, the annual OSAS-related collisions, costs, and
      fatalities in the United States and performs a cost-benefit analysis of treating
      drivers suffering from OSAS with continuous positive airway pressure (CPAP).
      DESIGN: The MEDLINE-PubMed database (1980 to 2003) was searched for information
      on OSAS. A meta-analysis was performed of studies investigating the relationship
      between collisions and OSAS. Data from the National Safety Council were used to
      estimate OSAS-related collisions, costs, and fatalities and their reduction with
      treatment. Next, the annual cost of treating OSAS with CPAP was calculated.
      Finally, multiple 1-way sensitivity analyses were performed. SETTING: N/A.
      PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: More
      than 800,000 drivers were involved in OSAS-related motor-vehicle collisions in
      the year 2000. These collisions cost 15.9 billion dollars and 1,400 lives in the
      year 2000. In the United States, treating all drivers suffering from OSAS with
      CPAP would cost 3.18 billion dollars, save 11.1 billion dollars in collision
      costs, and save 980 lives annually. CONCLUSION: Annually, a small but significant
      portion of motor-vehicle collisions, costs, and deaths are related to OSAS. With
      CPAP treatment, most of these collisions, costs, and deaths can be prevented.
      Treatment of OSAS benefits both the patient and the public.

PMID- 15164899
TI  - Inspiratory airflow dynamics during sleep in women with fibromyalgia.
AB  - STUDY OBJECTIVES: To determine whether women with fibromyalgia have inspiratory
      airflow dynamics during sleep similar to those of women with upper-airway
      resistance syndrome (UARS). DESIGN: A descriptive study of consecutive female
      patients with fibromyalgia. SETTING: An academic sleep disorders center. PATIENTS
      OR PARTICIPANTS: Twenty-eight women with fibromyalgia diagnosed by
      rheumatologists using established criteria. Fourteen of the women gave a history
      of snoring, while 4 claimed to snore 'occasionally' and 10 denied snoring. The
      comparison group comprised 11 women with UARS matched for age and obesity.
      INTERVENTIONS: Eighteen of the 28 women with fibromyalgia and all of the women
      with UARS had a full-night polysomnogram. All participants had a nasal continuous
      positive airway pressure (CPAP) study with quantitative monitoring of inspiratory
      airflow and effort between atmospheric pressure and therapeutic CPAP. Fourteen
      patients with fibromyalgia and all patients with UARS had a successful
      determination of pharyngeal critical pressure. MEASUREMENTS AND RESULTS: Twenty
      seven of 28 women with fibromyalgia had sleep-disordered breathing. One of the 27
      had obstructive sleep apnea hypopnea while 26 had milder inspiratory airflow
      limitation with arousals. One patient had no apnea or hypopnea or inspiratory
      airflow limitation during sleep. While the patients were sleeping at atmospheric
      pressure, apnea-hypopnea index, arousal index, the prevalence of flow-limited
      breaths, and maximal inspiratory flow were similar between groups. The pharyngeal
      critical pressure of the patients with fibromyalgia was -6.5 +/- 3.5 cmH2O (mean
      +/- SD) compared to -5.8 +/- 3.5 cmH2O for patients with UARS (P = .62).
      Treatment of 14 consecutive patients with nasal CPAP resulted in an improvement
      in functional symptoms ranging from 23% to 47%, assessed by a validated
      questionnaire. CONCLUSION: Inspiratory airflow limitation is a common inspiratory
      airflow pattern during sleep in women with fibromyalgia. Our findings are
      compatible with the hypothesis that inspiratory flow limitation during sleep
      plays a role in the development of the functional somatic syndromes.

PMID- 15164900
TI  - Sleep-disordered breathing is not associated with the presence of retinal
      microvascular abnormalities: the Sleep Heart Health Study.
AB  - STUDY OBJECTIVE: Sleep apnea and milder forms of sleep-disordered breathing (SDB)
      have been associated with overt clinical cardiovascular disease, but it is
      unknown whether SDB is associated with arterial microvascular pathology. We
      examined the relation between SDB and retinal microvascular abnormalities.
      DESIGN: Cross-sectional study. PARTICIPANTS: Subjects were 2,927 men and women,
      aged 51 to 97 years, who participated in the Sleep Heart Health Study and had
      retinal photographs taken within approximately 3 years of overnight, unattended,
      at-home polysomnography. MEASUREMENTS AND RESULTS: A respiratory disturbance
      index (RDI), calculated as the average number of apneas and hypopneas per hour of
      sleep, was used as an indicator of SDB in analysis. The overall prevalence of
      retinopathy was slightly higher in people with higher RDI values (5.4%, 4.9%,
      8.6%, and 7.6%, respectively, in increasing quartiles of RDI), but after
      adjustment for age, body-mass index, hypertension, diabetes, and other factors,
      the presence of retinopathy was not associated with SDB. With the possible
      exceptions of microaneurysms and generalized arteriolar narrowing, as measured by
      lower arteriole-to-venule ratio, specific retinal abnormalities were not
      associated consistently with the RDI. Relative to the first quartile of RDI, the
      adjusted odds ratios (95% confidence interval) for the presence of microaneurysm
      in the second, third, and fourth quartiles of RDI were 1.05 (0.44-2.55), 1.97
      (0.89-4.37), and 1.79 (0.78-4.10), respectively. An increase of RDI from 0 to 10
      was associated with a predicted decrease in arteriole-to-venule ratio of 0.01.
      Results were similar when analyses were conducted in normotensive and nondiabetic
      persons separately. CONCLUSIONS: These data do not demonstrate a notable relation
      between SDB and retinal abnormalities. However, since this is the first
      investigation of a link between retinopathy and SDB, similar studies should be
      conducted in other population samples to demonstrate either consistency or
      inconsistency of our findings across studies.

PMID- 15164901
TI  - Sleep-disordered breathing and white matter disease in the brainstem in older
      adults.
AB  - STUDY OBJECTIVES: To examine whether sleep-disordered breathing is associated
      with white matter disease in the brainstem. DESIGN: A population-based
      longitudinal study. SETTING: Allegheny County, PA; Sacramento County, CA; and
      Washington County, MD. PATIENTS OR PARTICIPANTS: A total of 789 individuals, aged
      68 years or older, drawn from the Sleep Heart Health Study. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: The participants underwent home polysomnography in 1995
      1998 and cerebral magnetic resonance imaging in both 1992-1993 and 1997-1998. The
      apnea-hypopnea index was not associated with white matter disease in the
      brainstem, with or without adjusting for age, sex, race, community, body mass
      index, smoking status, alcohol use, systolic blood pressure, and the use of
      antihypertensive medication. In contrast, the arousal index (number of arousals
      per hour of sleep) was inversely associated with brainstem white matter disease
      (odds ratio = 0.75 for a SD increase in the arousal index, 95% confidence
      interval: 0.62, 0.92). CONCLUSIONS: The frequency of apneas and hypopneas was not
      associated with brainstem white matter disease in these older adults. A unique
      relationship with arousal frequency suggests that ischemic changes in the
      brainstem may be associated with arousals during sleep.

PMID- 15164902
TI  - Exercise and sleep-disordered breathing: an association independent of body
      habitus.
AB  - STUDY OBJECTIVES: The degree to which physical exercise habits are related to
      sleep-disordered breathing is not known. We sought to investigate the association
      between a single-item exercise question and laboratory-assessed sleep-disordered
      breathing. DESIGN: A population-based cross-sectional epidemiologic study of
      adults measured the association between exercise and sleep-disordered breathing.
      Hours of weekly planned exercise were assessed by questionnaire. Sleep-disordered
      breathing was assessed by 18-channel in-laboratory polysomnography and
      characterized by the apnea-hypopnea index. SETTING: Polysomnography was conducted
      at the University of Wisconsin General Clinical Research Center sleep laboratory.
      PATIENTS AND PARTICIPANTS: Participants included 1104 men and women, aged 30 to
      60 years, enrolled in the Wisconsin Sleep Cohort Study. MEASUREMENTS AND RESULTS:
      Associations were modeled using linear and logistic regression, adjusting for
      body mass index, skinfold measurements, age, sex, and other covariates. Adjusted
      mean (95% confidence interval) apnea-hypopnea index was 5.3 (4.4, 6.2) events per
      hour for participants who exercised 0 hours per week; 3.9 (2.8, 5.0) events per
      hour for those with 1 to 2 hours of exercise; 3.2 (2.2, 4.2) events per hour for
      those with 3 to 6 hours of exercise; and 2.8 (1.0, 4.6) for those with > 7 hours
      of exercise (P trend < .001). Similarly, the odds of having moderate or worse
      sleep-disordered breathing (apnea-hypopnea index > 15 events per hour)
      significantly decreased with increasing level of exercise. CONCLUSION:
      Independent of measures of body habitus, lack of exercise was associated with
      increased severity of sleep-disordered breathing.

PMID- 15164903
TI  - Obstructive apneic events induce alpha-receptor mediated digital
      vasoconstriction.
AB  - STUDY OBJECTIVE: To characterize the role of alpha-receptors in autonomic control
      of digital skin blood flow change in response to obstructive apnea-hypopnea
      events. DESIGN: Experimental intervention study. SETTING: Sleep laboratory in a
      university hospital. PATIENTS: Eight male patients with severe obstructive sleep
      apnea (OSA). INTERVENTIONS: Patients received four cumulative dosage steps of
      phentolamine (0.066, 0.2, 2 and 5 [n=3] microg/min/100 ml forearm tissue) via
      brachial artery infusion during nonrapid eye movement sleep (stage 1 and 2).
      MEASUREMENTS AND RESULTS: The pulse amplitude determined with peripheral arterial
      tonometry (PAT) was periodically attenuated during the immediate post apnea
      hypopnea period coinciding with arousal. PAT ratio (smallest pulse amplitude post
      apnea divided by largest pulse amplitude during apnea), was determined as a
      measure of digital vasoconstriction. We found that, compared with baseline, PAT
      ratio dose-dependently increased during phentolamine (0.2, 2 and 5 microg)
      infusion by 11.2+/-1.7%, 24.4+/-2.1% and 30.9+/-4.1%, respectively (P<0.001).
      Systemic blood pressure and heart rate were largely unaffected by the
      pharmacological intervention. CONCLUSION: OSA related alteration of the pulse
      amplitude includes a constriction of digital skin vasculature that to a large
      extent is mediated via sympathoadrenergic alpha-receptors.

PMID- 15164905
TI  - Pediatric sleep disorders: exploratory modulation of their relationships.
AB  - STUDY OBJECTIVES: This study explores relationships between clinically
      encountered sleep problems in children. DESIGN: The Sleep Disturbance Scale for
      Children (SDSC) (Bruni et al 1996), which screens 26 sleep problems and results
      in 6 sleep disorder-subscales, was used as core in a larger health-behavior
      questionnaire (HBQ). PARTICIPANTS: Caregivers of 3045 6- to 12-year-olds filled
      out the HBQ. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 21 SDSC-items plus 15
      new sleep items were selected. Via structural equation modelling we explored (1)
      relations within and between disorder-subscales, (2) relations between the
      disorder-subscales with 3 indexes added (i.e., sleep efficiency index, sleep
      environment index, and sleep enuresis) and (3) relations of the disorder
      subscales to their categorization: dyssomnia and parasomnia, without and with the
      indexes. CONCLUSIONS: The final model had a satisfying fit and approximates the
      Association of Sleep Disorders Centers' classification. Each disorder-subscale
      can be applied individually. However, some items are statistically of low value.
      For that reason, the use as the inference of relations between such items should
      be cautious. Adding the 3 indexes improved the fit of the model. The complexity
      of 'sleep enuresis' was especially revealed. For the practicing care provider, as
      for researchers, the statistical model proposed could be a valuable directive in
      the diagnostic classification process of pediatric sleep problems.

PMID- 15164904
TI  - Response shift in perception of sleepiness in obstructive sleep apnea-hypopnea
      syndrome before and after treatment with nasal CPAP.
AB  - STUDY OBJECTIVES: After nasal continuous positive airway pressure (nCPAP)
      treatment, several symptoms such as hypersomnolence, daytime fatigue, and
      impaired concentration improve in patients with obstructive sleep apnea-hypopnea
      syndrome (OSAHS). A variability of perception of pretreatment sleepiness
      (response-shift phenomenon) experienced in OSAHS patients before and after nCPAP
      treatment may reflect informative shifts in an individual's internal standards,
      in values and priorities, or in the conceptualization of perceived sleepiness.
      The objective of this study is to determine whether there is a response shift in
      perceptions of pretreatment sleepiness before and after nCPAP treatment in
      patients with OSAHS. We investigated the response shift in Epworth Sleepiness
      Scale scores before and after nCPAP. DESIGN: Thirty-one consecutive OSAHS
      patients filled out the subjective ESS before nCPAP treatment (Pre-ESS). After a
      mean of about 10 months of nCPAP treatment, the patients filled out the ESS
      again, which was designated as the Post-ESS. Then they were asked to complete the
      scale again, recalling sleepiness before nCPAP treatment (Response Shift-Pre
      ESS). The control group consisted of 11 patients with OSAHS who had not yet
      received nCPAP treatments and were matched for age, body mass index, and
      respiratory disturbance index. SETTING: University Hospital in, Japan.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There was a significant response
      shift in ESS scores before and after nCPAP treatment (Pre-ESS: 8.5 [95%
      Confidence interval [CI], 7.1-9.9] vs Response Shift-Pre-ESS: 11.1 [95% CI, 9.5
      12.8], P < .002). A significant number of patients (P < .02) had not recognized
      the degree of sleepiness experienced before treatment until after they had
      received nCPAP treatment. Eight had pretreatment ESS scores > or = 11 and 18 had
      posttreatment ESS scores > or = 11 on the Response Shift-Pre-ESS. In the control
      group, ESS did not change significantly from the first to the second testing
      performed before nCPAP treatment (first ESS, 8.8 [95% CI, 5.3-12.3]; second ESS,
      8.3 [95% CI, 4.7-11.8]: P = .95). CONCLUSIONS: Response shifts should be taken
      into consideration when explaining factors underlying individual differences in
      susceptibility to daytime sleepiness.

PMID- 15164906
TI  - Peripheral arterial tonometry events and electroencephalographic arousals in
      children.
AB  - STUDY OBJECTIVES: Peripheral arterial tonometry (PAT) is a sensitive measure of
      moment-to-moment changes in sympathetic activity and reliably identifies arousals
      in adult subjects. We investigated whether PAT events during sleep are associated
      with visually recognizable electroencephalographic arousals in healthy children
      and in children with sleep-disordered breathing. DESIGN: Prospective cohort.
      SETTING: Pediatric Sleep Research Laboratory. PARTICIPANTS: Twenty children with
      obstructive sleep apnea syndrome, 20 children with mild sleep-disordered
      breathing, and 20 control children with a mean age of 7.6 +/- 2.6 years (range:
      5.7-16.5 years); 53% of children were boys. INTERVENTIONS AND MEASUREMENTS:
      Polysomnographic evaluation in the sleep laboratory with concomitant recording of
      PAT. PAT events were defined as attenuations from immediately preceding baseline
      of 20% to 50% (PAT20) and > 50% (PAT50) for at least 5 seconds and the indexes
      calculated per hour of sleep time that included good-quality PAT signals. Total
      PAT index (the sum of PAT20 index and PAT50 index) was also calculated. RESULTS:
      Total PAT index correlated with total arousal index and spontaneous arousal index
      (r = 0.55, P < .0001, r = 0.64, P < .001, respectively), especially in the group
      with obstructive sleep apnea syndrome (r = 0.71, P < .0001). The sensitivity and
      specificity of PAT for identifying electroencephalographic arousals were 95% and
      35%, respectively. The PAT device identified pathologic arousals indexes (> or =
      16 per hour) (area under the curve 0.79, P = .002). Thirty-five percent of
      respiratory events (eg, obstructive apnea or hypopnea) were associated with a
      visual electroencephalographic arousal, compared to 92% being associated with PAT
      attenuation events. CONCLUSIONS: Arousals in sleeping children are associated
      with increased sympathetic discharge, as evidenced by attenuations in PAT signal.
      However, a significant proportion of PAT attenuations were not accompanied by
      visual electroencephalographic arousals. Thus, the importance of these autonomic
      arousals has yet to be explored in association with morbidities related to sleep
      disordered breathing and, therefore, PAT technology cannot be recommended as an
      alternative tool for measuring arousals in children. Nevertheless, these data
      further support the contention that adult criteria for the measurement for
      arousals may not be adequate in children.

PMID- 15164907
TI  - Mother-infant bedsharing is associated with an increase in infant heart rate.
AB  - OBJECTIVES: We hypothesized that mother-infant bed sharing, compared to solitary
      sleeping, would be associated with higher infant heart rates. The objective was
      to compare infant heart rates between the 2 environments and, secondarily, to
      test for relationships between heart rate and other, previously reported,
      differences in the same infants. DESIGN: Heart rate was measured in 15 infants
      over a bed-sharing night and a solitary-sleeping night. Eight of the 15 infants
      routinely bed shared with the mother at home; the other 7 routinely slept in a
      room alone. SETTING: The Sleep Disorders Center, University of California, Irvine
      Medical Center. PARTICIPANTS: Fifteen mother-infant pairs who met criteria for
      routinely bed sharing or sleeping solitarily. All were healthy, and infants were
      more than 38 weeks gestation at birth and 11 to 15 weeks old at the time of the
      study. INTERVENTIONS: None. RESULTS: Analysis of variance indicated that,
      irrespective of routine sleeping condition, heart rate was lower during solitary
      sleeping than during bed sharing in all sleep stages. Significant regressions
      were found with infant temperature. Heart-rate variability was higher during
      solitary sleeping than during bed sharing (both routine groups) in stages 1 and 2
      and rapid eye movement sleep, but only stages 1 and 2 sleep effects were
      independent of basal heart rate. CONCLUSIONS: Infant heart rate is affected by
      the mother's presence in the sleep environment. The increase in sympathetic
      activity in stages 3 and 4 and rapid eye movement sleep might be partly explained
      by differences in thermoregulation between bed-sharing and solitary-sleeping
      environments. These results support the notion that sensory differences between
      bed-sharing and solitary-sleeping environments account for some of the
      physiologic differences between infant sleep in the 2 sleeping conditions.

PMID- 15164908
TI  - Correlates of sleep-wake patterns among children and young adolescents in Taiwan.
AB  - STUDY OBJECTIVE: To determine correlates of morning and evening sleep-wake
      patterns in a community sample of children. DESIGN: A school-based cross
      sectional survey. PARTICIPANTS: Sample included 1572 students, grades 4 to 8
      (response rate, 98.4%), using a multistage sampling method. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Student participants completed a Sleep Habits
      Questionnaire, which included sleep schedules, a mood scale, substance use, the
      morningness/eveningness (M/E) scale, pubertal development scale, sleep
      disturbance scale, and parental monitoring scale. The morning (n = 367) and
      evening (n = 364) groups were operationally defined as participants who scored in
      the top or bottom 25% of the M/E scale, respectively. Linear mixed and tree-based
      classification models were used to explore correlates of sleep-wake patterns. Our
      results showed the evening type was associated with older school grade level,
      increased coffee drinking, moodiness, decreased parental monitoring, daytime
      sleepiness, and several sleep disturbances, including early insomnia, fear of
      sleeping in darkness, bedwetting, and going to bed later than 3 am. The 2 most
      potent discriminators between evening and morning subtypes were higher grade
      level, an index of age, and moodiness. The association of moodiness with the
      evening type was greater in boys than girls. CONCLUSIONS: These findings suggest
      that further research should address explanations for the association between
      evening type and mood and anxiety symptoms, including order of the effects,
      developmental factors, environmental determinants of sleep time such as school
      start time and parental bedtime monitoring, and circadian maturation.

PMID- 15164909
TI  - Snoring, sleep quality, and sleepiness across attention-deficit/hyperactivity
      disorder subtypes.
AB  - STUDY OBJECTIVES: To characterize the relationship between pediatric attention
      deficit/hyperactivity disorder (ADHD) subtypes, chronic snoring, and indexes of
      sleep quality and daytime sleepiness. DESIGN: A cross-sectional design with
      planned comparisons of ADHD (all subtypes) versus general community controls;
      ADHD Predominantly Inattentive Type (ADHD-I) versus a group with both ADHD
      Predominantly Hyperactive/Impulsive Type (ADHD-HI) and ADHD Combined Type (ADHD
      C); and ADHD-HI versus ADHD-C. SETTING: Subjects recruited from a pediatric
      clinic, a university psycholgy clinic, and the general community. PARTICIPANTS:
      Caretakers of 74 children (45 with ADHD, 29 community controls; 53 boys, 21
      girls; mean age, 9.6 years; age range, 6 to 16 years). Thirty-two (71.1%) of the
      children with ADHD were taking stimulant medication and 7 (15.5%) were taking
      hypnotic medication. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Caretakers
      completed the Pediatric Sleep Questionnaire (PSQ) and the Children's Sleep-Wake
      Scale (CSWS). Only the ADHD-HI diagnosis was associated with an increased
      likelihood of chronic snoring. Sleep quality was poorer among children with ADHD
      than controls; however, there were no differences in sleep quality across ADHD
      subtypes. Sleepiness was greater in children with ADHD, especially the ADHD-I
      Type. CONCLUSIONS: Chronic snoring may be a correlated feature in only a subgroup
      of the ADHD population, possibly those more likely to be diagnosed with ADHD-HI.
      Although children with ADHD have poorer sleep quality and greater daytime
      sleepiness, these 2 features of ADHD are not closely related.

PMID- 15164910
TI  - Impact of spouses' sleep problems on partners.
AB  - STUDY OBJECTIVES: To analyze relationships between spouses' sleep problems and
      their partners' physical health, mental health, well-being, social involvement,
      and marital quality in a sample of older persons. DESIGN: The Alameda County
      Study is a population-based longitudinal study focusing on behavioral factors
      associated with health and mortality. SETTING: Participants completed
      questionnaires for the sixth wave of data collection (1999). PARTICIPANTS: 405
      couples (810 husbands and wives aged 51 to 94 years). MEASUREMENTS AND RESULTS:
      Participants were asked how often they had experienced difficulty falling asleep,
      waking up in the middle of the night, and waking up very early in the morning
      over the past month. Response sets ranged from "never" to "often." Scores were
      summed. Analyses included multivariate statistical models using generalized
      estimating equations to adjust for paired data as well as partner age, sex,
      chronic conditions, financial problems, and own sleep problems. Although
      partners' associations with negative outcomes were stronger for their own sleep
      problems, spouses' sleep problems were associated with partners' poor health,
      depressed mood, poor mental health, unhappiness, low optimism, feeling left out,
      not satisfied with relationships, and unhappy marriage, even after adjusting for
      the partners' sleep problems. We found no sex differences in associations between
      spouses' sleep problems and partners' outcomes. CONCLUSIONS: Although data are
      cross-sectional, findings suggest that spouses' sleep problems negatively impact
      partners' health and well-being. Our analyses emphasize the importance of
      treating sleep problems to promote the health and well-being of both affected
      individuals and their partners.

PMID- 15164911
TI  - Polysomnography performed in the unattended home versus the attended laboratory
      setting--Sleep Heart Health Study methodology.
AB  - STUDY OBJECTIVE: To compare polysomnographic recordings obtained in the home and
      laboratory setting. DESIGN AND SETTING: Multicenter study comparing unsupervised
      polysomnography performed in the participant's home with polysomnography
      supervised at an academic sleep disorders center, using a randomized sequence of
      study setting. Sleep Heart Health Study (SHHS) standardized polysomnographic
      recording and scoring techniques were used for both settings. PARTICIPANTS: 64 of
      76 non-SHHS participants recruited from 7 SHHS field sites who had both a
      laboratory and home polysomnogram meeting acceptable quality criteria.
      MEASUREMENTS AND RESULTS: Median sleep duration was greater in the home than in
      the laboratory (375 vs 318 minutes, respectively, P < .0001) as was sleep
      efficiency (86% vs 82%, respectively, P < .0024). Very small, but significant
      increases in percentage of rapid eye movement sleep and decreases in stage 1
      sleep were noted in the laboratory. Employing multiple definitions of respiratory
      disturbance index (RDI), median RDI was similar in both settings (for example,
      RDI with 3% desaturation: home 12.4, range 0.6-67; laboratory 9.5, range 0.1
      93.4, P = .41). Quartile analysis of laboratory RDI showed moderate agreement
      with home RDI measurements. Based on the mean of laboratory and home RDI and
      using a cutpoint of 20, there was a biphasic distribution, with the RDI 3% above
      20 being more common in the recordings performed in the laboratory than in the
      home and below 20 being more common in the recordings performed in the home than
      in the laboratory. These differences could not be attributed to quality of
      recording, age, sex, or body mass index. CONCLUSIONS: Using SHHS methodology,
      median RDI was similar in the unattended home and attended laboratory setting
      with differences of small magnitude in some sleep parameters. Differences in RDI
      between settings resulted in a rate of disease misclassification that is similar
      to repeated studies in the same setting.

PMID- 15164913
TI  - Radiofrequency surgery of the soft palate in the treatment of snoring: a review
      of the literature.
AB  - STUDY OBJECTIVES: Radiofrequency surgery of the soft palate presents a promising
      alternative for the treatment of snoring. The aim of this study was to give an
      overview of the current literature and to quantify the results in terms of a meta
      analysis of treatment efficacy. METHODS: Current databases were searched for
      publications concerning the treatment of snoring with radiofrequency surgery up
      to January 2003. Only original articles published in peer-reviewed journals were
      taken into consideration. RESULTS: The review is based on 22 publications, mostly
      consisting of prospective noncontrolled clinical trials. Snoring was assessed
      with the help of visual analogue scales or snoring scores provided by the bed
      partner. In all these trials, a significant reduction of snoring was reported.
      Postoperative morbidity was low, but complication rates differed substantially.
      CONCLUSIONS: According to all of the published material, radiofrequency surgery
      of the soft palate leads to a significant reduction of subjective snoring, and
      snoring is reduced to a tolerable level. Nevertheless, these findings will have
      to be confirmed by controlled clinical trials.

PMID- 15164912
TI  - A pictorial sleepiness scale based on cartoon faces.
AB  - STUDY OBJECTIVES: To develop a sleepiness scale devoid of semantic or geometric
      elements. DESIGN: Subjects were asked to rank in order 7 cartoon faces
      representing degrees of sleepiness. We used Thurstone's scaling procedure to
      transform these rankings into an interval scale, which allowed us to eliminate 2
      of the faces. The remaining 5 faces were ranked again using other subjects. In a
      validation study, subjects rated their perceived level of sleepiness using our
      scale and other sleepiness scales. Employed shiftworkers and school-going
      children used our scale to assess its practical applicability. SETTINGS: Research
      and diagnostic sleep laboratories, pre-primary to tertiary institutions, shift
      working industry. PARTICIPANTS: Ethnically diverse healthy and sleep-disordered
      adults (n = 490), and school-going children (n = 345). MEASUREMENTS AND RESULTS:
      Our faces scale correlated with the Karolinska Sleepiness Scale (P < .05), the
      Stanford Sleepiness Scale (P < .04), and a visual analog scale measuring
      sleepiness (P < .0001). Shiftworkers showed a time-on-task effect on the evening
      shift (P < .0001) and a peak in sleepiness at 4:00 and 5:00 (P < .0001) on the
      night shift. Eight to 10 year old children appeared sleepier than older children
      throughout a school day (P < or = .02) and became sleepier as the day progressed
      (P < .0001). We confirmed that our scale measures sleepiness, uncontaminated by
      pain, anger, or happiness. CONCLUSIONS: We have devised a sleepiness scale
      suitable for people too young or insufficiently educated to employ more
      conventional scales. We envisage the scale being used for diagnostic,
      therapeutic, and research purposes.

PMID- 15164914
TI  - Practice parameters for the dopaminergic treatment of restless legs syndrome and
      periodic limb movement disorder.
AB  - Dopaminergic agents, particularly dopamine agonists, have been used with
      increasing frequency in the treatment of restless legs syndrome and periodic limb
      movement disorder. These evidence-based practice parameters are complementary to
      the Practice Parameters for the Treatment of Restless Legs Syndrome and Periodic
      Limb Movement Disorder, published in 1999. These practice parameters were
      developed by the Standards of Practice Committee and reviewed and approved by the
      Board of Directors of the American Academy of Sleep Medicine. Recommendations are
      based on the accompanying comprehensive review of the medical literature
      regarding the dopaminergic treatment of restless legs syndrome (RLS) and periodic
      limb movement disorder (PLMD), which was developed by a task force commissioned
      by the American Academy of Sleep Medicine. The following recommendations serve as
      a guide to the appropriate use of dopaminergic agents in the treatment of RLS and
      PLMD. Levodopa with decarboxylase inhibitor, and the dopaminergic agonists
      pergolide, pramipexole, and ropinirole are effective in the treatment of RLS and
      PLMD. Other dopamine agonists (talipexole, cabergoline, piribidel, and alpha
      dihydroergocryptine) and the dopaminergic agents amantadine and selegiline may be
      effective in the treatment of RLS and PLMD, but the level of effectiveness of
      these medications is not currently established. Lastly, no specific
      recommendations can be made regarding dopaminergic treatment of children or
      pregnant women with RLS or PLMD.

PMID- 15164915
TI  - An update on the dopaminergic treatment of restless legs syndrome and periodic
      limb movement disorder.
AB  - This paper reviews evidence from April, 1998 through April 2002 for the
      dopaminergic treatment of the restless legs syndrome (RLS) and periodic limb
      movement disorder (PLMD). There has been increased study of dopaminergic agents
      for the treatment of these conditions since publication of a review paper and
      practice parameters that covered all types of medical treatment of RLS and PLMD
      in 1999. For this reason, the Restless Legs Syndrome Task Force and the Standards
      of Practice Committee decided to update the evidence on dopaminergic treatment of
      these conditions. This paper reviews the literature on levodopa, dopaminergic
      agonists (pergolide, pramipexole, ropinirole, talipexole, cabergoline, piribidel,
      DHEC), and other dopaminergic agents (amantadine, selegiline).

PMID- 15164916
TI  - Preoperative evaluation for obstructive sleep apnea.

PMID- 15164917
TI  - Thermal expansion typed investments for casting titanium.
AB  - New investments for titanium were developed by adding ZrC and ZrN as additives
      for thermal expansion to an MgO cement base investment with setting shrinkage and
      low thermal expansion. Setting, thermal and residual expansion, X-ray diffraction
      and compressive strength of these experimental investments, surface roughness of
      the cast plate and casting accuracy of titanium crowns were evaluated. Thermal
      expansion of investments increased with additive amounts, and residual expansion
      occurred even when cooling to room temperature after firing in an air atmosphere
      by the oxidation to ZrO2 of these additives. The casting accuracy of full-crowns
      cast into molds at room temperature correlated with the content of ZrC and ZrN.
      As the result the cast titanium crown could be obtained with low surface
      roughness and good adaptability.

PMID- 15164918
TI  - Influence of a thickness and processing method on the linear dimensional change
      and water sorption of denture base resin.
AB  - The purpose of this study was to evaluate the influence of a thickness and
      processing method on linear dimension change and water sorption in a denture base
      resin after storage in water for 24 hours, one week, and four weeks. Sixty wax
      specimens 65 mm long and 10 mm wide were fabricated in three thicknesses, 1.5, 3,
      and 4.5 mm. Three dimples were made in each wax specimen. A travelling microscope
      was used to measure the total distance from the uppermost dimple to the lowest
      dimple to the nearest 0.01 mm. Acrylic resin blocks were polymerized with 2
      processing cycles (short and long-cured). Immediately after processing, all
      samples were measured by the same investigator. They were then weighed by an
      electronic precision balance capable of measuring to 0.001 g. Data were analyzed
      by analysis of variance. Thickness and time of storage were statistically
      significant on the dimensional change (linear and weight changes) of denture-base
      resin (p < 0.01), showing the influence of the processing method.

PMID- 15164919
TI  - Polymerization characteristics of EMA-based resin.
AB  - To explore the feasibility of a new relining material, polymerization
      characteristics such as peak temperature, setting time, residual monomer, and
      postpolymerization were examined in ethyl methacrylate (EMA) resins composed of
      EMA and 4 kinds of EMA/methyl methacrylate (MMA) copolymers with high and low
      molecular weights and initiated by benzoyl peroxide/N,N-dimethyl-p-toluidine
      system and compared with those of MMA/PMMA resins. Peak temperature (53.8-71.0
      degrees C) and residual monomer (2.56-3.52% after 1 h and 1.57-2.31% after 24 h)
      of the EMA resins were significantly lower than those of the MMA resins (88.9
      93.4 degrees C and 4.61-5.85% after 1 h and 4.09-4.84% after 24 h, respectively).
      The composition of the copolymers had a significant effect on peak temperature
      and setting time but no significant effect on residual monomer and
      postpolymerization. The molecular weight of the copolymers affected peak
      temperature, setting time and residual monomer significantly. This study
      suggested that EMA resins are worthy of further evaluation as a relining
      material.

PMID- 15164920
TI  - Retention force of complete palate coverage and palate-less dentures in vitro.
AB  - The purpose of this study was to investigate the retention force of complete
      palate coverage and palate-less dentures made with three polymerization systems
      (DS system, SR-Ivocap system, microwave polymerization system) in vitro. The
      retention force between each denture and a polyurethane model by intervening
      artificial saliva was measured using a tensile tester. In addition, discrepancies
      between the denture base and the stone cast were measured at several points. The
      retention force of complete palate coverage and palate-less dentures made with
      the 3 polymerization systems shows that the DS system had a greater retention
      force than the SR-Ivocap system and the microwave system. Moreover, the retention
      force of palate-less dentures was greater than that of complete dentures only in
      the case of the DS system. The interaction of the polymerization system and the
      denture type also had a statistically significant effect on the retention force.
      Dentures made with the DS system had smaller discrepancies compared with dentures
      processed with the other systems. The retention force correlated very closely
      with discrepancies at the denture border and the residual ridge.

PMID- 15164921
TI  - Application of dentition and facial morphology integration system for occlusal
      correction.
AB  - A system to provide quantitative information on the angle between dentition and
      face was developed using a three-dimensional (3D) integrated configuration
      measured by a non-contact 3D digitizer. The integrated configuration angles
      between the Camper's plane and occlusal plane on the sagittal and the horizontal
      projected planes were obtained. Clinical application for a patient to improve the
      tegmenta of the anterior tooth by setting a temporary bridge on her lower
      dentition was attempted. Her dentition and face were measured on her first visit
      and after treatment, and 3D data of them were integrated. The quantitative change
      of the angle between the Camper's plane and lower occlusal plane were
      successfully analyzed by the present system, and after treatment, rotation of the
      lower occlusal plane for 1 degrees in a clockwise direction on the sagittal plane
      projection, and that for 1 degrees in a counterclockwise direction on the
      horizontal plane projection relative to the Camper's plane were detected.

PMID- 15164922
TI  - Effects of silane coupling agent amount on mechanical properties and hydrolytic
      durability of composite resin after hot water storage.
AB  - The purpose of this study was to evaluate the effects of the silane coupling
      agent amount on the flexural properties and hydrolytic durability on an
      experimental composite resin for understanding the optimum amount of silanation.
      A spherical filler was silanated with 7 different amounts of gamma-MPTS, 0, 0.17,
      0.34, 0.66, 1.36, 2.72 and 5.45 mass%. Photopolymerized experimental composite
      resins were made from a 70/30 mass% of UDMA/TEGDMA and a 65 mass% of different
      silanated amounts of filler. Bar-shaped specimens were prepared for a 3-point
      bending test in 37 degrees C water after 1-day water storage at 37 degrees C and
      after an additional 1, 7, and 28 days hot water storage in Soxhlet's extractor.
      The flexural strength and flexural modulus of unsilanated filler dramatically
      decreased after 28 days hot water storage while those of silanated filler showed
      a slight change. These results suggested that the silanated amount on the silica
      filler is not sensitive for flexural properties and hydrolytic stability of
      composite resin.

PMID- 15164923
TI  - Machinability evaluation of titanium alloys.
AB  - In the present study, the machinability of titanium, Ti-6Al-4V, Ti-6A1-7Nb, and
      free-cutting brass was evaluated using a milling machine. The metals were slotted
      with square end mills under four cutting conditions. The cutting force and the
      rotational speed of the spindle were measured. The cutting forces for Ti-6Al-4V
      and Ti-6Al-7Nb were higher and that for brass was lower than that for titanium.
      The rotational speed of the spindle was barely affected by cutting. The cross
      sections of the Ti-6Al-4V and Ti-6Al-7Nb chips were more clearly serrated than
      those of titanium, which is an indication of difficult-to-cut metals. There was
      no marked difference in the surface roughness of the cut surfaces among the
      metals. Cutting force and the appearance of the metal chips were found to be
      useful as indices of machinability and will aid in the development of new alloys
      for dental CAD/CAM and the selection of suitable machining conditions.

PMID- 15164924
TI  - Study of resin-bonded calcia investment. Part 3: Hardness of titanium castings.
AB  - The Vickers hardness of the cross-sectioned area of titanium castings made from
      an experimental resin-bonded calcia investment and three commercial investments
      was evaluated. The microstructure and element distribution of the surface zone
      were analyzed using an EPMA. The results showed that the high hardness of the
      casting surface could be decreased using the experimental investment. The
      hardness of the castings made from the experimental investment at a 25-50 microm
      depth was lower than those from the other investments, and the thickness of the
      hardened casting surface was 125 microm. Layered structures with fewer layers
      were formed on the surfaces of the castings made from the experimental
      investment. The layered structures were influenced by both the investment
      components and the mold temperature at casting. The less contaminating nature of
      the experimental investment components and the technology of the room temperature
      mold contributed to the improved surface properties of the resulting castings.

PMID- 15164925
TI  - Determination of the fabricating conditions for the preferable marginal and
      internal adaptation of the mica crystal castable ceramic crown.
AB  - This study was performed to find an acceptable internal adaptation of castable
      ceramics containing mica and beta-spodumene crystals. The influences of factors,
      expansion rate of phosphate-bonded investment (A), anisotropic expansion (B),
      diecoating (C), shrinkage during crystallization (D), and interaction (A x B),
      and (A x C) were tested by twice repeated experiments under block design
      according to L8(2)(7) orthogonal array. Estimated mean ranges under the
      conditions combined with significant factors were judged by considering the
      criteria of the ideal internal gap (about 50 microm). The ideal marginal fit of
      less than 50 microm and uniform cement space about 50 microm around the axial
      wall could be achieved by a combination of optimum levels of A1B1C2D2. However,
      the estimated mean gap at the cusp tip and central fossa of occlusal inside by
      this combination were about 120 microm. The near intolerable gaps could not be
      reduced.

PMID- 15164926
TI  - [Interstitial pneumonitis and serum markers (SP-D & KL-6) in collagen vascular
      diseases].

PMID- 15164927
TI  - [Role of dendritic cells in the immunopathogenesis and therapy of liver
      diseases].

PMID- 15164928
TI  - [Pathogenesis and treatment of psoriasis vulgaris].

PMID- 15164929
TI  - [Development of immunotherapy for cancer: lessons from melanoma research].
AB  - Identification of human melanoma antigens by various molecular biological and
      immunological techniques and evaluation of tumor reactive T cells in patients
      with the identified tumor antigen and HLA tetramer technology, not only provided
      us more profound understanding of anti-tumor immune responses in human, but also
      led to reveal basic problems in each step towards immunological tumor rejection,
      including systemic suppressive mechanisms such as regulatory T cell induction and
      local inhibitory environment in tumors. Based on these results obtained from the
      basic and clinical researches, various improvements have been applied for
      immunotherapy, including active immunization with modified antigenic peptides and
      recombinant virus, T cell adoptive transfer with lymphodepletive pretreatment,
      and administration of anti-CTLA-4 Ab, although further improvement is necessary.
      The translational research performed on melanoma, would facilitate development of
      immunotherapy for other cancers.

PMID- 15164930
TI  - [The effectiveness of cevimeline hydrochloride on dry cough in Sjogren's
      syndrome].
AB  - Dry cough in Sjogren syndrome (SS) is not an uncommon symptom observed in
      clinical fields. However, effective treatments for the cough have not been
      established. The recently introduced cevimeline hydrochloride, a muscarinic
      receptor stimulant, has been confirmed to be definitely effective for xerostomia
      of SS. In the present study, the effectiveness of cevimeline hydrochloride on dry
      cough was studied in 9 Sjogren patients and evaluated using the visual analog
      scale (VAS) and face scale. Improvement of dry cough was observed in 8 out of the
      9 patients, suggesting the effectiveness of cevimeline hydrochloride. Although
      the detailed etiology of dry cough in SS is unknown, the result of the study
      suggested the mechanism that cevimeline hydrochloride increased the secretion in
      the airway mucus, improving dry bronchial conditions. Further studies are needed
      with more subjects.

PMID- 15164931
TI  - [A case of amyopathic dermatomyositis with acute interstitial pneumonia (DAD
      pattern)].
AB  - A 61-year-old man was admitted to our hospital because of edematous erythema on
      his upper eyelids and dry cough. No subjective nor objective findings suggestive
      of skeletal muscle involvement, such as muscle weakness and elevated levels of
      aldolase and creatine phosphokinase were noted. Chest high-resolution computed
      tomography revealed a ground glass opacity and consolidation of his lower lung.
      Skin biopsy findings were compatible with dermatomyositis. Therefore, he was
      diagnosed as amyopathic dermatomyositis (ADM) with acute interstitial pneumonia
      and treatment with steroid pulse therapy was started. Since histological
      evaluation showed diffuse alveolar damage during the initial treatment, the
      treatment was changed into the combination therapy of prednisolone and
      cyclosporine. However, his acute interstitial pneumonia did not respond to this
      treatment and passed away by aggravation of a breathing state and concurrence of
      disseminated intravascular coagulation. Japanese patients with ADM have been
      shown to be more frequently associated with intractable acute interstitial
      pneumonia than Caucasian patients, suggesting that the racial difference
      influences the occurrence of acute interstitial pneumonia in ADM. Since
      autoantibodies specific for ADM have not been detected, we performed
      immunoprecipitation analysis using 35S methionine-labeled K562 cells to identify
      them. His sera immunoprecipitated a polypeptide of 140 kDa. The 140 kDa
      polypeptide might be one of autoantibodies specific for ADM with acute
      interstitial pneumonia, although future analysis using a larger number of
      patients with ADM will be required to confirm this result.

PMID- 15164932
TI  - [Regulation of apoptosis by p53].

PMID- 15164933
TI  - [Current status and perspective of mass screening for prostate cancer in Japan].

PMID- 15164934
TI  - [A study on the factors influencing the anxiety of family members in the
      emergency department].
AB  - The purpose of this study was to determine the factors which affect anxiety of
      family members in the emergency department (ED). 174 family members of patients
      participated in this study. The age of family members was a mean of 43.1 (range:
      20 to 84) years and 59.8% of them were women. The informations were obtained from
      a questionnaire filled out by the family members when they were waiting during
      examination and treatment of the patients. In this study, we divided the factors
      that influence the anxiety of family members into 4 categories; demographic
      factors, the family's individual factors, factors associated illness, and
      environmental factors in the ED. Multiple regression analysis with SPSS was used
      to identify the variables contributing to the variance in anxiety. We used the
      State Anxiety Inventory (S-STAI) to measure anxiety. As a result, 8 variables
      involving in severity of illness, situation in the emergency room, disagreement
      between perceived severity of illness and actual severity of illness, having
      symptoms of trauma, neurological, heart, and respiratory problems, waiting time,
      family needs, naturally anxious personality and a first visit patient were
      identified as significant predictors of anxiety. These variables accounted for
      46.9% of total variance. These results suggest that nurses need more interaction
      with family members to reduce their anxiety.

PMID- 15164935
TI  - Marriage and contraception among the Pare of northern Tanzania.
AB  - The purpose of the research reported here is to examine the connection between
      contraception and those aspects of a woman's position that are related to her
      marriage. The research was conducted in two villages among the Pare of northern
      Tanzania where a shift from hoe cultivation as primary occupation to wage labour
      has brought about major changes in social relations. The major hypothesis is that
      a change from a 'traditional' marital union to a 'companionate' marriage is
      instrumental in the acceptance of contraception and in lowering fertility. The
      latter type of relationship between marital partners is related to the status of
      women. The research methodology consisted of a combination of an ethnographic
      study, demographic surveys and in-depth interviews. Findings show that
      approximately half of the women in this community ever used contraception. Of
      current users, a third are sterilized and half are using a modern reversible
      method. The determining factor for using modern reversible methods is the nature
      of the conjugal union.

PMID- 15164936
TI  - Abortion as a backup method for contraceptive failure in China.
AB  - Contraceptive failure rates for modern methods including sterilization are
      reported to be high in China, but little is known about the consequence of
      contraceptive failure and characteristics of women who decide to have an abortion
      if a contraceptive failure occurs. Using 6225 contraceptive failures from the
      1988 Chinese Two-per-Thousand Fertility Survey, this study examines the
      resolution of contraceptive failure and assesses the impact of some women's
      sociodemographic characteristics on the decision to terminate contraceptive
      failure in abortion. This study has three important findings: (1) The abortion
      rate was 50.1%, 75.3% and 80.2% for IUD, condom and pill failures, respectively;
      (2) The abortion rates differed by contraceptive method and women's social and
      demographic characteristics. In particular, a woman with just one child was most
      likely to have the contraceptive failure aborted; (3) Some women experienced
      repeated abortions because of contraceptive failure. The results suggest that
      abortion was a backup method if contraception failed in China and the correlates
      of aborting an unwanted pregnancy reflect the strong impact of the Chinese family
      planning programme.

PMID- 15164937
TI  - A social component in the negative effect of sons on maternal longevity in pre
      industrial humans.
AB  - Due to their effect on maternal testosterone levels, sons are said to have
      reduced maternal longevity in pre-industrial humans. This analysis, using
      information from a Flemish agricultural village in the 18th-20th centuries,
      confirms the presence of a negative effect of sons on maternal longevity.
      However, the effect is mainly observed for mothers belonging to the least
      privileged social group and for sons surviving their fifth birthday. Both
      findings make the above-mentioned biological explanation relative. However, a
      plausible alternative, social interpretation is male-dominated intra-household
      resource competition. It is reasonable to assume that only sons above a certain
      age are able to claim a serious amount of resources and that competition is
      strongest within the least privileged social group.

PMID- 15164938
TI  - Birth seasonality in the Old Order Amish.
AB  - The Old Order Amish are a healthy and well-nourished natural fertility
      population, so that the timing of births is not influenced by behaviours to limit
      family size, undernutrition or disease. The present study examines the monthly
      distribution of 8160 births occurring between 1920 and 1991 in the Geauga
      Settlement in north-east Ohio, USA. The monthly distribution of births in the
      Geauga Settlement is bimodal, with a major peak extending from August to October,
      a minor peak in February, and a major trough from April to June. This pattern is
      almost identical to the pattern found in the US in 1943. The monthly distribution
      of first births appears to be influenced to some extent by a highly significant
      seasonal pattern of weddings. The pattern of births in the Old Order Amish is
      consistent with the hypothesis that the spring trough in US births is at least
      partially caused by a decrease in coital frequency and/or a decrease in
      fecundability as a result of hot summer temperatures but is not consistent with
      the hypothesis that the fall peak in US births is primarily due to an increase in
      coital frequency during the Thanksgiving and Christmas holiday seasons.

PMID- 15164939
TI  - Gender difference in daily time and space use among Bangladeshi villagers under
      arsenic hazard: application of the compact spot-check method.
AB  - The compact spot-check method was applied to elucidate the daily time and space
      use patterns of 121 adults from a Bangladeshi village in which the authors had
      previously found more skin manifestations due to arsenic poisoning in males than
      females. The analysis of 2178 spot-check data, which were obtained over a net
      period of 2 days, highlighted that farming and cash-earning activities were
      almost exclusively conducted by males. This is probably due to the Muslim
      Bangladeshi norm for females to be 'sedentary' in or around their own dwellings.
      Discussion focuses on the advantages of the compact spot-check method and the
      possibility that males' larger energy expenditure and longer exposure to sunlight
      are responsible for their severer skin manifestations.

PMID- 15164940
TI  - Cognitive ability and occupational status in a British cohort.
AB  - The relation between individual trait differences, social mobility and social
      structure is central to social biology. Because genetic variance underlies
      phenotypic variance in some of these traits, for example IQ, several mechanisms
      determine the population variance. Polygenic inheritance is the basic mechanism.
      Social mobility and assortative partner choice distribute the trait variance
      within generations. This feedback circle is constrained by sociological
      conditions at several levels of analysis. Fundamental to this theory of social
      assortment is the relation between social-biological traits and social class on
      the one hand, and these traits and social mobility on the other hand. The focus
      here is on the relation between social class, social mobility and cognitive
      ability. The National Child Development Study is drawn upon, including the last
      follow-up (1999-2000). By approaching this relationship through various methods,
      both social-biological and sociological aspects of this research question can be
      assessed.

PMID- 15164941
TI  - Fertility transition in Bangladesh: understanding the role of the proximate
      determinants.
AB  - Bangladesh has been passing through a crucial phase of fertility transition. The
      level of fertility declined dramatically during the early 1990s without any
      remarkable improvement in socioeconomic and health status, and then remained
      constant at a high level of 3.3, despite the increased use of contraception. Such
      fertility transition can be traced to variations in one or more of the proximate
      or direct determinants of fertility. This paper critically analyses the fertility
      levels in Bangladesh with a view to exploring the possible explanations of
      fertility decline in the 1990s and then its stabilization. The main focus of the
      study is to examine the role of the major proximate determinants of fertility in
      bringing about the change in fertility level in Bangladesh. The data for the
      study come from a series of nationally representative surveys over the period of
      1975 to 1999-2000. The analysis indicates that fertility has temporarily ceased
      to decline in recent years due to the 'tempo' effect of high past fertility, but
      in general a declining trend in fertility is underway. The analysis suggests that
      the fall in fertility is consistent with the underlying trends in most important
      proximate determinants of fertility. In recent years contraception has emerged as
      the highest fertility reducing factor in Bangladesh and its effect is greatest in
      middle and older age groups. Although until the early 1990s postpartum
      lactational infecundability was the most important and strongest fertility
      reducing factor in Bangladesh, in recent years its fertility inhibiting effect
      has gradually decreasing owing to the declining trend in the lactational
      infecundability period. The analysis reveals that although the fertility reducing
      effect of the marriage pattern is increasing, its effect is offset by the
      declining trend in the lactational infecundability period. A review of these two
      variables suggests that their effect cannot be raised much for prevailing
      socioeconomic and cultural reasons, and any future reduction in fertility in
      Bangladesh may be largely dependent on increased use of effective birth control
      methods.

PMID- 15164942
TI  - The sexual orientation of men who were brought up in gay or lesbian households.
AB  - Elsewhere the author has suggested that adolescent and adult male homosexual
      orientation is, in some cases, causally associated with sexual or quasi-sexual
      experience in childhood (James, 2004). Here it is argued that the available data
      on men raised by same-sex parents cannot validly be interpreted as supporting or
      refuting this suggestion.

PMID- 15164943
TI  - Does nitric oxide contribute to iron-dependent brain injury after experimental
      cerebral ischaemia?
AB  - Experimental and clinical data suggest that iron has a key role in cerebral
      ischaemia. We measure infarct volume and analyse the nitric oxide responses to
      brain injury in rat stroke model after increased oral iron intake. Permanent
      middle cerebral artery occlusion (MCAO) was performed in a group of 20 male
      Wistar rats, 10 of which were fed with a control diet and 10 of which were fed
      with iron-enriched diet containing 2.5% carbonyl iron for 9 weeks. L-arginine and
      nitric oxide metabolites were determined in blood samples before and at 2, 6, 8
      and 48 h after MCAO. Infarct volume, thiobarbituric acid reaction substances
      (TBARS) and tissue iron were measured at 48 h. Infarct volume was 66% greater in
      the iron-fed rats than in the control group. Iron-fed animals showed
      significantly higher levels of TBARS. Liver iron stores (3500 +/- 199 vs 352 +/-
      28 microg Fe/g, p<0.0001) but not brain iron stores (131 +/- 11 vs 139 +/- 8
      microg Fe/g, p=0.617), were significantly higher in the iron-fed group. L
      arginine levels were slightly lower in iron-fed rats and decreased significantly
      in both groups at 6 and 8 hours after MCAO. The levels of the stable end products
      of NOS (NOx = nitrite + nitrate) were significantly higher in iron-fed rats
      before MCAO (16.2 +/- 2.2 vs. 9.6 +/- 0.8 micromol x L(-1), p<0.05), with a
      further increase during the six first hours after MCAO in both groups. These
      results suggest that the iron overload that increases both superoxide and nitric
      oxide production leads to peroxynitrite formation, thus enhancing brain damage.

PMID- 15164944
TI  - Cerebrospinal fluid S-100 protein levels in neurological pathologies.
AB  - The aim of this paper was to evaluate S-100 concentration in cerebrospinal fluid
      (CSF) from patients with different neurological disorders, and in subjects with
      no proven neurological pathology, in order to study possible differences in their
      protein concentrations. The total number of patient-samples examined was 119 (58
      males and 61 females; mean age 35 yrs, 1-79 yrs). Based on the final diagnoses,
      nine patient groups were studied: a control group, meningitis, acute lymphatic
      leukemia (ALL), dementia, hydrocephalia, polyneuropathy-motor neuron disease,
      acute cerebral infarction (ACI), and patients diagnosed with multiple sclerosis.
      S-100 protein concentrations were measured by the Sangtec 100 two-site
      immunoradiometric assay. The highest S-100 levels in CSF were found in the
      dementia group, ACI group, bacterial-fungal and lymphocytic meningitis groups
      (Kruskal-Wallis test). The S-100 concentrations in these groups were
      significantly higher compared with the control group (Mann-Whitney U test,
      p<0.05, p<0.01) and the multiple sclerosis group (p<0.05, p<0.01). No other
      significant differences were found between groups. Our results suggest that the
      high protein levels in CSF found in these pathologies may reflect the presence of
      brain damage. However, the levels need to be considered individually, as they
      depend on several factors, such as age, severity of brain damage or interval
      between the onset of brain damage and the taking of the sample.

PMID- 15164945
TI  - Effect of melatonin on the oxidative stress in N1E-115 cells is not mediated by
      mt1 receptors.
AB  - To explore if protective effect of melatonin on oxidative stress induced by
      okadaic acid, an inhibitor of protein phosphatases PP1 and PP2A, is mediated by
      membrane receptors subtype mt1, we used an in vitro model with N1E-115
      neuroblastoma cells. We demonstrated that exposure of cells to 50 nM okadaic acid
      for 2 h induces a reduction in the activity of antioxidative enzymes, and an
      increase of lipid peroxidation products, while melatonin prevents the effect of
      okadaic acid. On the other hand, the presence of luzindole, 20 min before adding
      melatonin, did not cause changes on the effect of the melatonin on oxidative
      stress. These results seem to indicate that protective effect of melatonin is not
      mediated by mt1 receptors.

PMID- 15164946
TI  - Purified angiotensin converting enzyme from Rana esculenta ovary influences
      ovarian steroidogenesis in vitro.
AB  - The aim of the present study was to purify and characterize angiotensin
      converting enzyme (ACE) present in frog ovary (Rana esculenta). Detergent and
      trypsin-extracted enzymes were purified using a one-step process, consisting of
      affinity chromatography on lisinopril coupled to Sepharose 6B. The molecular mass
      was 150 kDa for both detergent-extracted and trypsin-extracted enzyme. The
      specific activity of detergent-extracted and trypsin-extracted ACE was 294 U mg(
      1) and 326 U mg(-1) respectively. The optimum pH range was from 7-8.5 at 37
      degrees C and the optimum temperature was 50 degrees C. Optimum chloride
      concentration was about 200 mM for synthetic substrate FAPGG (N-[3-(2
      furyl)acryloyl] L-phenylalanyl glycyl glycine) and angiotensin I, and 10 mM for
      bradykinin. The Km and Kcat values for FAPGG were 0.608 +/- 0.07 mM and 249 sec(
      1) respectively and I50 values for captopril and lisinopril, two specific ACE
      inhibitors, were 68 +/- 12.55 nM and 6.763 +/- 0.66 nM respectively. Frog ovary
      tissue from prereproductive period was incubated in vitro in the presence of frog
      ovary ACE (2.5 mU/ml), captopril (0.1 mM), and lisinopril (0.1 mM). Production of
      17beta-estradiol, progesterone, and prostaglandins E2 and F2alpha was determined.
      The data showed a modulation of 17beta-estradiol, progesterone and prostaglandin
      E2 production by ovary ACE.

PMID- 15164947
TI  - Hemorheology and oxygen transport in vertebrates. A role in thermoregulation?
AB  - We studied the effect of temperature on blood rheology in three vertebrate
      species with different thermoregulation and erythrocyte characteristics. Higher
      fibrinogen proportion to total plasma protein was found in turtles (20%) than in
      pigeons (5.6%) and rats (4.2%). Higher plasma viscosity at room temperature than
      at homeotherm body temperature was observed in rats (1.69 mPa x s at 20 degrees C
      vs. 1.33 mPa x s at 37 degrees C), pigeons (3.40 mPa x s at 20 degrees C vs. 1.75
      mPa x s at 40 degrees C), and turtles (1.74 mPa x s at 20 degrees C vs. 1.32 mPa
      x s at 37 degrees C). This fact allow us to hypothesize that thermal changes in
      protein structure may account for an adjustment of the plasma viscosity. Blood
      viscosity was dependent on shear rate, temperature and hematocrit in the three
      species. A different behaviour in apparent and relative viscosities between rat
      and pigeon at environmental temperature was found. Moreover, the blood oxygen
      transport capacity seems more affected by a reduction of temperature in rats than
      in pigeons. Both findings indicate a greater influence of temperature on
      mammalian erythrocyte than on nucleated red cells, possibly as a consequence of
      differences in thermal sensitivity and mechanical stability between them. A
      comparison between the three species revealed that apparent blood viscosity
      measured at homeotherm physiological temperature was linearly related to the
      hematocrit level of each species. However, when measured at environmental
      temperature, rat blood showed a higher apparent viscosity than those found in
      species with non-nucleated red cells, thus indicating a higher impact of
      temperature decrease on blood viscosity in mammals. This suggest that regional
      hypothermia caused by cold exposure may affect mammalian blood rheological
      behaviour in a higher extent than in other vertebrate species having nucleated
      red cells and, consequently, influencing circulatory function and oxygen
      transport.

PMID- 15164948
TI  - Mitochondrial alkaline phosphatase as an intracellular signal in the synthesis of
      1,25(OH)2D3 and 24,25(OH)2D3 in LLC-PK1 cells.
AB  - In previous works we have found a mitochondrial alkaline phosphatase (AP)
      activity in LLC-PK1. The aim of this work has been to study the possible
      involvement of mitochondrial AP activity in the synthesis of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)
      from the substrate 25(OH)D3. Renal phenotype LLC-PK1 cells were incubated with
      25(OH)D3 as substrate and treated with or without 1,25(OH)2D3, forskolin, 12
      myristate-13-acetate (PMA) and 1,25(OH)2D3 in conjunction with PMA. Incubation of
      LLC-PK1 cells with forskolin (adenylate cyclase activator) not only stimulated
      the 1-hydroxylase and inhibited the 24-hydroxylase activities but also increased
      the mitochondrial AP activity. The addition of 1,25(OH)2D3, the main activator of
      24-hydroxylase, produced a decrease of mitochondrial AP activity, a decrease of
      1,25(OH)2D3 synthesis and an increase of the 24,25(OH)2D3 synthesis. Incubation
      with PMA, a potent activator of protein kinase C, did not produce any changes in
      mitochondrial AP activity, but an inhibition of 1,25(OH)2D3 and an activation of
      24,25(OH)2D3 synthesis were found. Moreover, incubation of LLC-PK1 cells with PMA
      in conjunction with 1,25(OH)2D3 produced an additive effect in the decrease of
      1,25(OH)2D3 and an increase of 24,25(OH)2D3 synthesis remaining mitochondrial AP
      activity as cells treated only with 1,25(OH)2D3. Our results suggest that
      mitochondrial AP activity could be involved as an intracellular signal in the
      regulation of 25(OH)D3 metabolism to the synthesis of 1,25(OH)2D3 and
      24,25(OH)2D3 in renal phenotype LLC-PK1 cells through cAMP protein kinase system.

PMID- 15164949
TI  - Influence of microcystin-LR on the activity of membrane enzymes in rat intestinal
      mucosa.
AB  - The objective of the present study was to evaluate the effects of microcystin-LR
      (MCLR) on the activity of membrane enzymes from intestinal mucosa. In addition,
      serum chemistry and peroxidative status of both serum and intestinal homogenate
      were evaluated after treatment with MCLR. Wistar rats were treated with
      intraperitoneal injection of either 100 microg pure MCLR/Kg body weight or saline
      solution. A significant increase in liver weight and altered serum enzyme
      activities were found in MCLR-treated rats, indicating damage to the liver in
      these rats, as previously suggested. A higher specific activity of sucrase (1.5
      fold) was observed after the administration of MCLR, whereas other intestinal
      apical membrane enzymes, such as lactase, maltase and alkaline phosphatase were
      not modified by the treatment. The specific activities of acid phosphatase and
      succinate dehydrogenase, markers for lysosomal and mitochondrial membranes,
      respectively, were also increased (32% and 60%, respectively) in treated rats.
      The analysis of lipid peroxidation showed that the peroxidative status was
      increased in both serum and intestinal mucosa from MCLR-treated rats, reflecting
      an excess production of oxygen free radicals induced by this cyanobacterial
      toxin. In conclusion, this study shows that acute exposure to MCLR affects the
      intestinal physiology by modifying the intestinal peroxidation status as well as
      the activity of membrane enzymes.

PMID- 15164950
TI  - Relation between leptin and body fat distribution in menopausal status.
AB  - We examined the serum concentrations of leptin in a homogeneous group of 52
      postmenopausal Mediterranean women, calculating body fat mass distribution by
      waist-to-hip circumference ratio (WHR) and other anthropometric measurements.
      Significant correlations were found between leptin and weight (r=0.59), Body Mass
      Index (BMI) (r=0.56), Conicity Index (CI) (r=0.49) and all circumferences
      measured: chest (r=0.55), waist (0.61) and hip (r=0.65), but not between leptin
      and WHR. Leptin levels does not seem to be influenced by fat mass distribution
      (android or gynoid type) while weight gain over life appears to be related with
      the hormone concentration when menopausal status is well established.

PMID- 15164953
TI  - A comparison study of quality of life in women with fibromyalgia and myofascial
      pain syndrome.
AB  - PURPOSE: To compare the quality of life scores of fibromyalgia patients with
      myofascial pain syndrome patients. METHOD: Thirty-three fibromyalgia patients, 33
      myofascial pain syndrome patients, and 33 age-matched controls completed Beck
      Depression Inventory and Short Form-36 questionnaires. RESULTS: Compared with
      myofascial pain syndrome patients, fibromyalgia patients reported significantly
      more often fatigue, numbness, tingling, gastrointestinal discomfort, and poor
      sleep. The mean scores on VAS and on Beck Depression Inventory were significantly
      higher in fibromyalgia patients than myofascial pain syndrome patients. Patients
      with fibromyalgia had significantly poorer health than the patients with
      myofascial pain syndrome in pain, general health, vitality, and role emotional
      subscales. CONCLUSIONS: The quality of life profile of fibromyalgia patients is
      quite different from those in the myosfascial pain syndrome group. Myofascial
      pain syndrome impacted mostly on physical health whereas fibromyalgia impacted on
      both physical and mental health.

PMID- 15164951
TI  - Molecular basis of 3-hydroxy-3-methylglutaric aciduria.
AB  - 3-Hydroxy-3-methylglutaric aciduria is a human autosomal recessive metabolic
      disorder that usually appears within the first year of life. The causes of this
      aciduria are lethal mutations in the gene encoding for 3-hydroxy-3-methylglutaryl
      coenzyme A lyase (HL). HL is a mitochondrial matrix enzyme that catalyzes the
      last step of ketogenesis and leucine catabolism. This gene has been mapped to
      chromosome 1 at locus 1pter-p33 and its genomic organisation comprises 9 exons
      whose sizes vary between 64-678 bp. The human cDNA sequence was reported in 1993
      with the first genetic study of two Acadian-French Canadian siblings. To date, 24
      mutations in 36 patients have been described; most of them are single-base
      substitutions causing amino acid replacements and a variety of splicing defects.
      In the population studied two mutations appear predominant: g.122GA (8 patients
      and 15 alleles) frequent in Saudi Arabia, and g.109GT (6 patients and 12
      alleles), prevalent in Spain. At least seven mutations are clustered in the
      second half of exon 2 affecting aminoacids E37, R41 and D42 and conforming a
      possible hot spot. The genotype-phenotype correlation is difficult to establish
      since the probands received different treatments, and the onset of an acute
      episode frequently depends on external factors such as fasting or acute illness.

PMID- 15164952
TI  - Prognostic social factors in the subacute phase after a stroke for the discharge
      destination from the hospital stroke-unit. A systematic review of the literature.
AB  - PURPOSE: The objective of our study was to identify prognostic social factors in
      the subacute phase after stroke for the discharge destination from the hospital
      stroke-unit. METHODS: A systematic literature search was performed, designed in
      accordance with the Cochrane Collaboration criteria. Internal, statistical and
      external validity of the studies were assessed using a checklist with 11
      methodological criteria. RESULTS: Characteristics of the social situation that
      proved to be important for prediction of the discharge destination are marital
      status and social support. Quantity and methodological quality of the research
      studies were insufficient, and the number of possible social prognostic factors
      investigated was limited by the absence of a conceptual framework of social
      subdomains in the studies, including an unambiguous definition of the prognostic
      social factors within these subdomains. CONCLUSIONS: A great need exists for
      research into the prognostic qualities of the following social factors: the
      ability to provide support, presence, and readiness of the homefront; the
      availability of professional care, personal financial means, membership of
      societies and clubs, frequency of contacts with close relatives and friends; the
      quality of the patient's residence with regard to the adaptation to the needs and
      abilities of the patient. A commitment about the aforementioned conceptual
      framework is mandatory.

PMID- 15164954
TI  - Dimensions of quality of life for Chinese adults with spinal cord injury: a
      qualitative study.
AB  - PURPOSE: The purpose of this study was to explore meaning and components of
      quality of life (QOL) perceived by Chinese adults with a spinal cord injury (SCI)
      and to examine the frame of reference that this population used to assess quality
      of their life. METHOD: A qualitative research approach was used. Six focus group
      interviews were conducted with 40 adults with SCI from a northeastern city in
      China. A content analysis was conducted on interview data to determine meaning
      and components of QOL perceived by the participants. RESULTS: Participants
      defined QOL as satisfaction with one's life, which might vary from person to
      person and change when the circumstance changed. They identified 18 QOL
      components that could be grouped into five domains: physical, psychological,
      economic, social well-being, and a least restrictive environment. When assessing
      quality of their life, participants used both internal (comparing with oneself)
      and external (comparing with others) comparisons. CONCLUSIONS: The results of
      this study contribute to the understanding of dimensions of QOL for people with
      SCI in China. Although several domains of QOL identified in the present study
      were similar to those found in previous studies conducted elsewhere, several
      unique components of QOL, such as relationship with extended family and
      neighbours, government support, peace in the world and the nation, were
      identified by the participants. These components appeared to be related to the
      Chinese culture and socioeconomic system. Specific QOL measurements that address
      these unique components are needed when assessing QOL of this population.

PMID- 15164955
TI  - Women on sickness absence--views of possibilities and obstacles for returning to
      work. A focus group study.
AB  - PURPOSE: The aim was to learn how women on sickness absence due to work related
      strain perceive and describe their possibilities and obstacles for returning to
      work. METHOD: The focus group method was used. Five groups were conducted and
      each group met at one occasion. Twenty women participated in total. RESULTS:
      Three different themes were found. In 'The process of losing control' the
      participants describe the process from controlling every day living, to total
      loss of control of private and working life. The second theme, 'Not finding
      alternatives', deals with the difficulties of finding an alternative way back to
      work. 'Mastering life as a whole' contains strategies for regaining control over
      daily activities and life as a whole. The results show that personal as well as
      environmental factors have an impact for returning to work. CONCLUSIONS: In this
      study we have received an understanding of the complex situation of being on
      sickness absence due to work related strain. We have learned the importance of
      recognizing the context of the individual and understanding the interplay between
      the person and the environment. As professionals in rehabilitation we can use
      this knowledge to create a rehabilitation programme supporting people back to
      work.

PMID- 15164956
TI  - Experiences of adolescents with cystic fibrosis during their transition from
      paediatric to adult health care: a qualitative study of young Australian adults.
AB  - PURPOSE: Exploring the experiences of Australian adolescents with Cystic Fibrosis
      (CF) as they made the transition from paediatric to adult care. This often
      traumatic change of care was examined from the perspective of the two types of
      care, paediatric and adult, elements of a transition programme if available and
      psychosocial factors that may affect the transition. METHOD: Focused-in-depth
      interviews were conducted with six young adults with CF (19-34 years), asking
      them to describe their experiences during the transition period. RESULTS:
      Thematic analysis of the transcribed interviews indicated that the four main
      areas that affected the transition experiences of the participants were
      paediatric and adult health care, the elements included in the transition
      programme, and psychosocial factors. CONCLUSIONS: The relationship of the patient
      with their paediatric doctor, the doctor's attitude towards the transition and
      the delivery of age-appropriate care appeared to influence the experiences of
      adolescents as they changed to adult care. Successful elements of a transition
      programme, if it was offered, were the orientation tours, the provision of
      information and the presence of a familiar face at adult clinics. Transition
      experiences of individuals had potential effects on their psychological and
      physical well-being so that, in order to maximize quality of care, health
      professionals must be aware of factors which may improve transition experiences.

PMID- 15164957
TI  - The international classification of functioning, disability and health and its
      application to cognitive disorders.
AB  - PURPOSE: This paper describes the conceptual foundation and systematic framework
      of the International Classification of Functioning, Disability, and Health (ICF)
      as a mechanism for understanding the course and consequences of various health
      related states. The specific application of the ICF with persons with cognitive
      dysfunction is also presented. METHOD: A comprehensive literature review related
      to the conceptualization of the ICF, its classification scheme and coding process
      is presented. Information on cognitive disorders including prevalence, functional
      manifestations and the assessment of a person's cognitive functioning and the
      applicability of the ICF's holistic classification and coding of cognitive
      dysfunction within the components of body structure and function, activity and
      participation, and environmental attributes is also reviewed. CONCLUSION: The ICF
      has the potential to classify and interpret cognitive deficits on a global level
      and thereby reflects upon the overall health and functioning of the individual in
      major life activities. The coding system systematically organizes measures
      related to the person's cognitive status and the resulting functional outcomes.
      The ICF focuses on individuals' performance of activities in all aspects of life
      and validates the independence and well-being of persons with disabilities making
      it an important instrument to be used by rehabilitation professionals.

PMID- 15164958
TI  - A picture of amputees and the prosthetic situation in Haiti.
AB  - PURPOSE: The purpose of this study is to present the situation of Haitian
      amputees and to outline some of the major barriers in Haiti that prevent people
      from receiving prosthetic treatment. METHOD: Interviews were conducted with
      amputees throughout Haiti using a 42-question questionnaire. Additionally,
      interviews were conducted with traditional healers, health care workers, and
      leaders of handicap associations. Each interview was manuscripted and the data
      were subsequently coded and analysed in the USA. RESULTS: There are three full
      time prosthetic shops and two part-time prosthetic shops in Haiti, all of which
      are severely limited in the scope of services they are able to provide amputees
      due to insufficient supplies and inadequately trained personnel. Only 25% of the
      164 amputees interviewed had ever had a prosthetic limb. Typically prosthetic
      treatment is inaccessible and unaffordable for amputees, which prevents many from
      seeking treatment. The most common cause of amputation in Haiti is infection,
      followed by motor vehicle accidents. CONCLUSION: There must be additional
      cooperation between Haitian patients, doctors, traditional healers, prosthetists,
      and government officials in order to provide more adequate prosthetic care.
      Prosthetic treatment in Haiti can be successful with cooperation of different
      entities, proper rehabilitation therapy, adequately trained personnel, and
      development of culturally appropriate limbs.

PMID- 15164959
TI  - Antibiotic resistance from two perspectives: man and microbe.
AB  - Despite much effort, antibiotic resistance continues to increase. Looking back,
      it is clear that this was an inevitable consequence of antibiotic use. From a
      bacterial viewpoint, the introduction of antibiotics was a tremendous stimulus to
      evolution. As a survival reaction to stress (selection pressure) bacteria, by
      means of their extreme biochemical and genetic versatility, have adapted to 21st
      Century conditions. Resistance can be to some extent contained by less and better
      use of antibiotics, but ultimately novel approaches to the treatment and
      prevention of infectious diseases will have to be forthcoming. This will only be
      achieved if best use is made of alternative resources presently available and
      most importantly, man's ingenuity must be fully engaged.

PMID- 15164960
TI  - Mechanisms of antibiotic neurotoxicity in renal failure.
AB  - Neurological complications of antibiotics are relatively common in renal failure.
      Central nervous system neurotoxicity due to penicillin and beta-lactam
      antibiotics is best documented with fewer accounts of ototoxicity, peripheral
      nerve toxicity and neuromuscular blockade. In the context of risk stratification,
      the goal of this review is to explore the mosaic of factors in renal impairment
      that may contribute to susceptibility to antibiotic neurotoxicity. Improved
      knowledge of the pathogenesis of these formidable adverse events among the renal
      failure subjects should help prevent antibiotic neurotoxicity in the future.

PMID- 15164961
TI  - PK-PD modelling of the effect of cefaclor on four different bacterial strains.
AB  - The effect of cefaclor against relevant bacterial strains was studied by
      employing a combined in vivo pharmacokinetic (PK)-in vitro pharmacodynamic (PD)
      approach. For this purpose selected isolates of Escherichia coli, Moraxella
      catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae were exposed in
      vitro to the interstitial cefaclor profile obtained in vivo in the interstitial
      space fluid of human tissue after administration of commonly used doses of
      cefaclor and the change in the number of colony forming units per millilitre
      (CFU/ml) versus time was monitored. Fitting of the data using a modified E(max)
      model resulted in a set of mean pharmacodynamic parameters (k0, k(max), EC50) for
      each bacterial strain. The parameters derived from these experiments were used in
      a computer-simulation of the antibacterial effects for different dosing regimens
      and formulations of cefaclor, notably an immediate (IR) and a modified (MR)
      release formulation. Dosage regimens were compared using the ratio between the
      number of bacteria remaining after 24 h of a given treatment (N24h). The results
      indicate that the number of bacteria of all investigated strains killed per day
      is equivalent when the same daily dose is administered twice a day with the MR
      dosage form than when given three times a day with the IR dosage form, in spite
      of the fact that the MR dosage form has approximately 20% lower bioavailability.
      Best results were obtained with the three-times a day regimen of the MR
      formulation. In conclusion, the present in vivo-PK/in vitro-PD simulations of the
      antimicrobial effects of cefaclor indicate that a twice-daily treatment with a MR
      formulation may offer a convenient and safe alternative to the conventional tid
      treatment.

PMID- 15164962
TI  - Effects of linezolid on staphylococcal adherence versus time of treatment.
AB  - Staphylococcus epidermidis has emerged as a major nosocomial pathogen that is
      often associated with infections of indwelling medical devices. Microbial
      adhesion to implanted foreign materials is a prerequisite for establishing
      infection. We studied the time-dependent anti-adhesion effects of linezolid and
      vancomycin on three S. epidermidis clinical isolates. Minimum inhibitory
      concentration (MIC) values were identical for both agents for all three isolates
      (2 mg/l). Bacterial suspensions were added to polystyrene wells and treated with
      0.5-4 times the MIC of linezolid or vancomycin at 0, 2, 4 or 6 h post
      inoculation. Supra-inhibitory (2 and 4 x MIC) and inhibitory (MIC) concentrations
      of linezolid demonstrated potent anti-adhesion activity following 2 and 4 h
      deferred treatments. Even at sub-inhibitory concentrations (0.5 x MIC),
      suppression of staphylococcal adherence to polystyrene was still evident in most
      cultures. Linezolid at two and four times the MIC also exerted significant
      inhibitory effects in cultures that had been treated with a 6-h delay. Supra
      inhibitory and inhibitory concentrations of vancomycin administered 2 h post
      infection appeared equally effective as linezolid. However, sub-inhibitory
      concentrations of vancomycin showed minimal or no activity against bacterial
      adhesion. When vancomycin treatments were delayed by 4 h, only concentrations
      above the MIC prevented adherence. Linezolid has promising in vitro anti-adhesion
      activity that merits further studies to determine its role in the management of
      foreign-body infections.

PMID- 15164963
TI  - Efficacy of ertapenem against methicillin-susceptible Staphylococcus aureus in
      complicated skin/skin structure infections: results of a double-blind clinical
      trial versus piperacillin-tazobactam.
AB  - Staphylococcus aureus is the predominant pathogen in complicated skin/skin
      structure infections. In this analysis of a subgroup of data from a randomised,
      double-blind trial, the efficacy of ertapenem 1 g daily was compared with
      piperacillin-tazobactam 3.375 g Q6H for treatment of complicated skin/skin
      structure infections caused by methicillin-susceptible S. aureus (MSSA). Of the
      529 treated patients in this trial, 185 (35.0%) had MSSA as a baseline pathogen.
      At the test of cure assessment 10-21 days post-therapy, 54 of 67 (80.6%) protocol
      evaluable patients in the ertapenem group and 55 of 68 (80.9%) in the
      piperacillin-tazobactam group were cured (odds ratio: 1.0 (95% confidence
      interval (CI): 0.4-2.4), P = 0.99). In both treatment groups, cure rates were
      higher in patients with monomicrobial than polymicrobial infections, but the
      difference was not significant. In this subgroup analysis of patients with MSSA
      complicated skin/skin structure infections, therapy with ertapenem 1 g daily was
      as effective as piperacillin-tazobactam 13.5 g divided in four daily doses.

PMID- 15164965
TI  - In vitro combined bactericidal activity of cefpirome and glycopeptides against
      glycopeptides and oxacillin-resistant staphylococci.
AB  - Infections caused by coagulase-negative staphylococci are becoming increasingly
      important, particularly those of nosocomial origin, as the organisms are
      frequently multi-resistant. New antimicrobial strategies are needed. The
      bactericidal activity of a combination of cefpirome with either vancomycin or
      teicoplanin against 12 strains of methicillin-resistant staphylococci with a
      decreased susceptibility to teicoplanin was determined in vitro by a time killing
      method. Strains Mu3 and Mu50 of Staphylococcus aureus were also studied.
      Cefpirome (0.125-0.5 x MIC) combined with vancomycin (0.25-1 x MIC) or
      teicoplanin (0.125-1 x MIC) acted synergically against 12 isolates over 18 h in
      most cases. A synergistic killing effect was also observed with the Mu3 and Mu50
      strains of glycopeptide-intermediate S. aureus but over a longer period.

PMID- 15164964
TI  - Antibiotic susceptibility of bacteria most commonly isolated from bone related
      infections: the role of cephalosporins in antimicrobial therapy.
AB  - Bone infections, which can be acute or chronic, often require aggressive
      antibiotic therapy, whether treated at home or in the community. Surveillance
      programmes are essential tools in the monitoring of antimicrobial resistance and
      can act as a resource to maintain effective prescribing. The Surveillance Network
      (TSN), which collects organism and patient-specific data from a network of
      laboratories across the United States, was used to analyse susceptibility of
      common bacterial species isolated from bone infections during 2000-2002. Narrow
      spectrum antimicrobials such as vancomycin, quinupristin-dalfopristin and
      linezolid demonstrated good activity against Staphylococcus aureus and
      streptococci, and were active against 100% of isolates. However, Gram-negative
      species were also commonly isolated from these sites of infection. Later
      generation cephalosporins, represented by ceftriaxone, cefotaxime and cefepime,
      exhibited a broad spectrum of activity including Enterobacteriaceae, streptococci
      and methicillin-susceptible S. aureus, but they were not active against
      methicillin-resistant S. aureus (MRSA) and showed variable activity against
      Pseudomonas aeruginosa. Using ceftazidime as a marker for extended spectrum beta
      lactamase (ESBL) expression, less than 3% of Escherichia coli or Klebsiella
      pneumoniae expressed this phenotype. Based on current in vitro activity, the
      third-generation cephalosporins provide broad-spectrum coverage useful for the
      empirical therapy of suspected bone infections, especially for patients treated
      in the community or hospitalised with community-acquired infections.

PMID- 15164966
TI  - Antimicrobial resistance among non-fermentative Gram-negative bacilli isolated
      from the respiratory tracts of Italian inpatients: a 3-year surveillance study by
      the Italian Epidemiological Survey.
AB  - The Italian Epidemiological Survey evaluated antibiotic susceptibility of non
      fermentative Gram-negative bacilli isolated from inpatient respiratory-tract
      specimens collected throughout Italy during 1997-1999. The minimal inhibitory
      concentrations of 14 antibiotics for 1474 Pseudomonas aeruginosa strains, 307
      Stenotrophomonas maltophilia strains and 114 Acinetobacter baumannii strains were
      determined in 57 clinical microbiology laboratories by means of a standardised
      micro-dilution method. The most active drugs against P. aeruginosa isolates were
      meropenem (81% susceptible) and amikacin (80% susceptible). Imipenem and
      meropenem proved to be the only agents active against A. baumannii isolates,
      although 13 and 16%, respectively, of strains were resistant to these drugs.
      Trimethoprim-sulphamethoxazole (TMP-SMZ) showed activity only against S.
      maltophilia isolates (83% susceptible). A total of 185 multidrug-resistant P.
      aeruginosa isolates (resistant to piperacillin, ceftazidime, gentamicin, and
      imipenem) were found. Resistance rates and trends showed consistent regional
      variations, including sharp increases from 1997 to 1999 in imipenem resistance
      among P. aeruginosa isolates from central and southern Italy.

PMID- 15164968
TI  - Antibiotic resistance and epidemiological typing of Staphylococcus aureus strains
      from ovine and rabbit mastitis.
AB  - Mastitis is a serious problem for sheep and rabbit farms, Staphylococcus aureus
      being the main causal agent. Fifty strains of S. aureus isolated from sheep and
      rabbits from farms located in diverse geographical regions of Spain were studied.
      Their resistance pattern and plasmid profile was related to the pulsotypes
      obtained by pulsed-field gel electrophoresis (PFGE). The results showed great
      heterogeneity in staphylococci isolated from sheep, both in pulse-type and
      plasmid profile. We found in addition, antibiotic-resistant strains and
      aminoglycoside-modifying enzyme (AGMEs) producer strains. The genotypes
      corresponding to staphylococci isolated from rabbits were less heterogeneous,
      although they also could be subdivided by plasmid profile and resistance
      patterns. Resistance to antibiotics such as methicillin or AGMEs production could
      indicate possible human origin of the strains or a possible source of resistant
      strains for human beings.

PMID- 15164967
TI  - A Klebsiella pneumoniae producing three kinds of class A beta-lactamases encoded
      by one single plasmid isolated from a patient in Huashan Hospital, Shanghai,
      China.
AB  - A Klebsiella pneumoniae strain was isolated from a sputum specimen of a patient
      in the intensive care unit in 1999 in Shanghai Huashan Hospital, China. The
      isolate was confirmed as an extended-spectrum beta-lactamase (ESBL) producing
      strain by double-disk synergy test. The results of susceptibility test showed
      that it was resistant to most beta-lactams (including third generation
      cephalosporins) and non-beta-lactam antimicrobial agents. Transconjugants were
      obtained at a frequency of 10(-4). A plasmid of about 60 kb was obtained from the
      transconjugant by plasmid extraction. Three major nitrocefin-hydrolysing bands
      with pIs of 5.4, 8.2 and 8.4, were shown in extracts of the transconjugant.
      Partial gene amplification products of bla(TEM), bla(SHV), and CTX-M-1 group gene
      were obtained from the isolate as well as its transconjugant. The entire
      bla(TEM), bla(SHV), and bla(CTX-M) in the transconjugant were amplified by PCR
      and the PCR products were cloned into a pHSG398 vector. Afterwards, the
      susceptibility of transformants and activities of beta-lactamases of
      transformants on antibiotics were tested. The PCR products were directly
      sequenced, analysed and identified as TEM-1, SHV-12, and CTX-M-3 genes. These
      results confirm that this strain of Klebsiella pneumoniae produces SHV-12, CTX-M
      3 ESBLs and TEM-1 beta-lactamase, encoded by one single plasmid, which is
      responsible for the resistance of this strain to most beta-lactams.

PMID- 15164969
TI  - Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor
      risedronate on Trypanosoma cruzi.
AB  - We present the results of the first detailed study of the molecular and cellular
      basis of the antiproliferative effects of the bisphosphonate risedronate (Ris) on
      Trypanosoma cruzi, the causative agent of Chagas' disease. Ris and related
      compounds, which block poly-isoprenoid biosynthesis at the level of farnesyl
      pyrophosphate synthase, are currently used for the treatment of bone resorption
      disorders, but also display selective activity against trypanosomatid and
      apicomplexan parasites. Ris induced a dose-dependent effect on growth of the
      extracellular epimastigote form of T. cruzi; complete growth arrest and cell
      lysis ensued at 150 microM. Growth inhibition was associated with depletion of
      the parasite's endogenous sterols, but complete growth arrest and loss of cell
      viability took place before full depletion of these compounds, suggesting that
      disappearance of other essential poly-isoprenoids is involved in its anti
      parasitic action. Ris had a variety of effects on cellular ultrastructure,
      including mitochondrial swelling, disorganisation of other organelles, such as
      reservosomes and the kinetoplast, together with the appearance of autophagic
      vesicles and progressive vacuolization of the cytoplasm. Ris had selective
      antiproliferative effects against the clinically relevant amastigote form of T.
      cruzi, and at 100 microM, was able to prevent completely the development of T.
      cruzi infection of murine muscle heart or Vero cells, and to cure cultures which
      were already infected. Ris induced drastic ultrastructural alterations in the
      intracellular parasites and blocked amastigote to trypomastigote differentiation,
      with no biochemical or ultrastructural effects on the host cells, which fully
      recovered their normal structure and activity after treatment. Ris is, therefore,
      a promising lead compound for the development of new drugs against T. cruzi.

PMID- 15164971
TI  - Population pharmacokinetics of gentamicin in hospitalized patients receiving once
      daily dosing.
AB  - The purpose of this study was to describe the population pharmacokinetics of
      gentamicin in a group of 939 adult hospitalized patients receiving once-daily
      administration of gentamicin and to evaluate the potential influence of patient
      covariates on gentamicin disposition. Data comprising 1294 serum concentrations
      from 939 patients, were analyzed using a nonlinear mixed-effect model (NONMEM).
      The patients had an average age of 55 and an average weight of 70 kg, 431 of the
      patients were female. The patient covariates including body weight, gender, age,
      and creatinine clearance (CL(CR)) were analyzed in a stepwise fashion to identify
      their potential influences on gentamicin pharmacokinetics. The data were best
      described with a two-compartment model. NONMEM analyses showed that gentamicin
      clearance (CL, l/h) was linearly correlated with CLcR with proportionality
      constant: 0.047 (S.E.: 0.0035) x CL(CR) (ml/min). Volume of the central
      compartment (V1, 1) was linearly related to body weight with proportionality
      constant: 0.28 (S.E.: 0.021) x body weight (kg). The mean population estimates of
      CL and V1 were 4.32 l/h and 19.61. respectively. The inter-individual variability
      in CL and V1 were 29.6 and 5.8%, respectively. Residual errors were 0.23 mg/l and
      23.7%. The mean population values of CL and V1 of gentamicin dosed once daily are
      in agreement with those described by others. This analysis indicates that once
      daily dosing (7 mg/kg) of gentamicin should achieve satisfactory concentration in
      patients with normal renal function although serum concentration monitoring is
      required to confirm the optimal dosing interval in patients with impaired renal
      function.

PMID- 15164970
TI  - Antiparasitic activity of risedronate in a murine model of acute Chagas' disease.
AB  - We report the results of a study on the activity of the farnesyl-pyrophosphate
      synthase inhibitor risedronate (Ris) in a murine model of acute Chagas' disease.
      This compound displays rapid, cytocidal activity in vitro against Trypanosoma
      cruzi, but its in vivo activity had not been investigated previously. A murine
      model of acute Chagas' disease was used, in which experimental animals were
      infected with 10(3) trypomastigotes and intravenous treatment was started 24 h
      post-infection. In this model, Ris, at doses as low as 1 mg/kg per day given for
      7 days, induced > 90% reductions in parasitaemia and increased very significantly
      (P = 0.001) the survival of treated animals. Higher doses (up to 10 mg/kg per
      day) led to further reductions in parasitaemia and mortality, with no deleterious
      effects on weight gain and general physical condition of the treated animals.
      There was no relapse of parasitaemia after discontinuation of treatment,
      suggesting trypanocidal, rather than trypanostatic, activity. This interpretation
      was confirmed by the almost complete disappearance of amastigote nests in the
      hearts of treated animals. However, no parasitological cures were observed in
      infected animals that received the bisphosphonate, probably due to the short
      treatment period. Taken together, these results indicate that Ris could be a
      useful lead compound for the development of new drugs effective against Chagas'
      disease.

PMID- 15164972
TI  - Antimicrobial susceptibility of Haemophilus influenzae, Haemophilus
      parainfluenzae and Moraxella catarrhalis isolated from adult patients with
      respiratory tract infections in four southern European countries. The ARISE
      project.
AB  - Over a 7-month period in 2000-2001, 1213 Haemophilus influenzae, 112 Haemophilus
      parainfluenzae and 142 Moraxella catarrhalis isolates were recovered from adult
      patients with respiratory tract infections. Patients were from four southern
      European countries (Spain, Italy, Portugal and Greece). The antimicrobial
      susceptibility of the isolates to 11 antibiotics was determined in a central
      laboratory. The most active drugs on the basis of MICs were levofloxacin,
      cefditoren, cefotaxime, cefpodoxime and amoxicillin/clavulanate. MICs > or = 2
      mg/l for amoxicillin were found in 19.5, 28.6, and 75.4% of H. influenzae, H.
      parainfluenzae and M. catarrhalis isolates, respectively. Isolates of H.
      influenzae and H. parainfluenzae with reduced susceptibility or that were fully
      resistant to amoxicillin/clavulanate, cefuroxime and clarithromycin were detected
      (0.2-1.8%) as well as M. catarrhalis resistant to clarithromycin (0.7%). Regular
      surveys of resistance patterns for antimicrobial agents are necessary.

PMID- 15164973
TI  - Fusidic acid resistance in community isolates of methicillin susceptible
      Staphylococcus aureus and the use of topical fusidic acid: a retrospective case
      control study.
AB  - Resistance to fusidic acid among community methicillin susceptible Staphylococcus
      aureus (MSSA) isolates in the United Kingdom and prescriptions for fusidic acid
      have both doubled over the past 6 years. A retrospective case-control study was
      undertaken to test the hypothesis that the use of topical fusidic acid is
      associated with the isolation of resistant organisms. A statistically significant
      association was found between fusidic acid resistance in MSSA isolates and
      exposure to topical fusidic acid (odds ratio: 2.77, 95% CI 1.01-7.93, P = 0.027).
      This study demonstrates for the first time an association between the use of
      topical fusidic acid and resistance at the individual patient level and supports
      the hypothesis that the observed increase in resistance is causally associated
      with the increased use of topical fusidic acid.

PMID- 15164974
TI  - Efficacy of two modalities of triple HIV therapy: probable superiority of
      indinavir.
AB  - The introduction of the so-called highly active antiretroviral therapies has had
      an impact on the natural history of the HIV infection. The aim of this
      contribution is to assess the differences in terms of plasma viral load (VL), as
      a reflection of therapy success or failure. A retrospective study was made of the
      changes in VL in two cohorts of patients depending on the drugs included in the
      triple therapy prescribed to them. The comparison of the triple therapies
      containing any reverse transcriptase inhibitor and different protease inhibitors,
      indinavir (IDV) (239 patients) versus saquinavir (SQV) or ritonavir (RTV) (138
      subjects), showed a significantly higher percentage of patients reaching a 'non
      detectable' VL among those receiving indinavir (67.8% versus 54.3%; P = 0.011).
      The interval before VL levels rose above 30,000 RNA copies/ml was different in
      the two groups: 385 days (276-495 days) for therapies including indinavir, and
      239 days (86-391 days) for saquinavir or ritonavir. This seems to support the
      excellent behaviour of indinavir when its efficiency is compared with other
      protease inhibitors acting as potential competitors.

PMID- 15164975
TI  - Evaluation of a triple-drug combination for treatment of experimental multidrug
      resistant pneumococcal meningitis.
AB  - To evaluate the therapeutic efficacy of ceftriaxone + vancomycin + rifampicin
      (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant
      strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or
      vancomycin 20 mg/kg), double-drug regimens (ceftriaxone + vancomycin [CV] and
      ceftriaxone + rifampicin [CR]) and a triple-drug combination (CVR) with or
      without dexamethasone were compared in a rabbit meningitis model. Meningitis was
      induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant
      (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the
      bacterial concentration at 24 h, and the bacterial killing rate was also
      evaluated. All combination regimens were superior to ceftriaxone or vancomycin
      single-drug regimens with regard to sterilisation of CSF and bacterial killing
      rate. Rifampicin was as effective as combination regimens. Regardless of
      dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV.
      CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would
      not have additional therapeutic benefit over CR during the initial 24 h of
      treatment.

PMID- 15164976
TI  - Improved method of detection of beta-lactam antibiotic-induced VCM-resistant MRSA
      (BIVR).

PMID- 15164977
TI  - Genotoxicity of benzene and its metabolites.
AB  - The potential role of genotoxicity in human leukemias associated with benzene
      (BZ) exposures was investigated by a systematic review of over 1400 genotoxicity
      test results for BZ and its metabolites. Studies of rodents exposed to
      radiolabeled BZ found a low level of radiolabel in isolated DNA with no
      preferential binding in target tissues of neoplasia. Adducts were not identified
      by 32P-postlabeling (equivalent to a covalent binding index <0.002) under the
      dosage conditions producing neoplasia in the rodent bioassays, and this method
      would have detected adducts at 1/10,000th the levels reported in the DNA-binding
      studies. Adducts were detected by 32P-postlabeling in vitro and following high
      acute BZ doses in vivo, but levels were about 100-fold less than those found by
      DNA binding. These findings suggest that DNA-adduct formation may not be a
      significant mechanism for BZ-induced neoplasia in rodents. The evaluation of
      other genotoxicity test results revealed that BZ and its metabolites did not
      produce reverse mutations in Salmonella typhimurium but were clastogenic and
      aneugenic, producing micronuclei, chromosomal aberrations, sister chromatid
      exchanges and DNA strand breaks. Rodent and human data were compared, and BZ
      genotoxicity results in both were similar for the available tests. Also, the
      biotransformation of BZ was qualitatively similar in rodents, humans and non
      human primates, further indicating that rodent and human genotoxicity data were
      compatible. The genotoxicity test results for BZ and its metabolites were the
      most similar to those of topoisomerase II inhibitors and provided less support
      for proposed mechanisms involving DNA reactivity, mitotic spindle poisoning or
      oxidative DNA damage as genotoxic mechanisms; all of which have been demonstrated
      experimentally for BZ or its metabolites. Studies of the chromosomal
      translocations found in BZ-exposed persons and secondary human leukemias produced
      by topoisomerase II inhibitors provide some additional support for this mechanism
      being potentially operative in BZ-induced leukemia.

PMID- 15164978
TI  - DNA double-strand break repair by homologous recombination.
AB  - DNA double-strand breaks (DSB) are presumed to be the most deleterious DNA
      lesions as they disrupt both DNA strands. Homologous recombination (HR), single
      strand annealing, and non-homologous end-joining are considered to be the
      pathways for repairing DSB. In this review, we focus on DSB repair by HR. The
      proteins involved in this process as well as the interactions among them are
      summarized and characterized. The main emphasis is on eukaryotic cells,
      particularly the budding yeast Saccharomyces cerevisiae and mammals. Only the
      RAD52 epistasis group proteins are included.

PMID- 15164980
TI  - Neuro-oncology in a nutshell.

PMID- 15164979
TI  - Advances in the application of germline tandem repeat instability for in situ
      monitoring.
AB  - Alterations in tandem repetitive DNA sequences such as minisatellite DNA and
      expanded simple tandem repeats (ESTRs) may provide useful biomarkers of induced
      germline effects. In this review, I describe the differences between ESTRs and
      minisatellites with respect to their structure and mutational mechanisms, and
      discuss field applications measuring induced germline instability. It is evident
      that both types of loci have high rates of mutation that facilitate the
      measurement of induced mutation measured in relatively small numbers of samples
      following environmentally relevant exposures. Several research groups have used
      these loci to demonstrate a significant increase in germline mutation in humans
      and animals exposed to radioactive or chemical pollutants in their natural
      environment. Mutations are manifested as gains or losses in repeat units and are
      detected either by pedigree screening or by PCR amplification of sperm DNA.
      Mutations at both ESTRs and minisatellites appear to arise via indirect
      mechanisms rather than by direct damage to the repeat locus itself. Most
      interestingly, ESTR instability following radiation has been shown to be
      heritable and transmitted to subsequent generations. An understanding of the
      mechanisms involved in induced instability is required in order to begin to
      decipher the potential biological implications of increased germline tandem
      repeat mutation. Furthermore, relatively few studies have investigated the
      ability of different genotoxins to induce tandem repeat instability. Such
      laboratory-based experiments will be crucial in clarifying the particular
      environmental or occupational exposures that should be targeted for future
      studies and for isolating and subsequently identifying the putative mutagens in
      complex environmental matrices.

PMID- 15164981
TI  - Analysis of the bHLH transcription factors Olig1 and Olig2 in brain tumors.
AB  - In the absence of specific markers, the histological diagnosis of
      oligodendroglial tumors is based on subjective qualitative criteria and remains
      controversial. Recently, two bHLH transcription factors involved in
      oligodendroglial specification, Olig1 and Olig2 have been proposed as potential
      markers of oligodendrogliomas. Expression of Olig1/2 was analyzed by in situ
      hybridization on 78 samples including 47 glial, 29 non-glial tumors, and two non
      tumoral brain tissues. Both genes had a similar pattern of expression. Olig1 and
      Olig2 were expressed in 26/30 (87%) and 28/30 (93%) of oligodendroglial tumors
      respectively but in only 9% of glioblastomas (1/11). Olig genes were also
      expressed in the low-grade fibrillary astrocytomas (4/4) and anaplastic
      astrocytomas (2/2). No expression was found in non-glial tumors, except for one
      primary cerebral lymphoma. Double staining with PLP, NFH, GFAP showed that olig
      genes were expressed by mature, non-tumoral oligodendrocytes, but not by normal
      astrocytes or neurones. This study indicates that Olig1/2 expression clearly
      distinguishes pure Olig-negative glioblastomas from a wide spectrum of Olig
      positive tumors including traditional oligodendrogliomas and oligoastrocytomas,
      glioblastomas with an oligodendroglial component (GBMO), and WHO grade 2 and 3
      astrocytomas. Because Olig genes have a crucial role in oligodendroglial
      determination, our data could be of help in defining the real spectrum of
      oligodendroglial tumors.

PMID- 15164982
TI  - Two different mechanisms of apoptosis resistance observed in interferon-beta
      induced apoptosis of human glioma cells.
AB  - Interferon (IFN)-beta is known to exert cytostatic or cytocidal effects in human
      glioma cells and is widely used in the treatment for gliomas. However, precise
      mechanisms of cell death induced by IFN-beta are not well understood. In this
      study, the authors investigated the intracellular signal transduction of IFN-beta
      in human glioma cells. The cell death process observed in susceptible cells SK-MG
      1 was accompanied by characteristic morphological changes of apoptosis,
      processing of caspases, and DNA fragmentation. Use of caspase inhibitors
      confirmed the activation of caspases, however activated executioner caspase was
      caspase-7 rather than caspases-3 or -6. Activation of DNA endonuclease, DNase
      gamma was also observed. Observation of other IFN-beta relatively resistant
      glioma cells (U251SP, T98G, U251MG, U87MG, SK-AO2) revealed two different
      mechanisms of apoptosis resistance. In contrast to T98G, U87MG, and SK-AO2 which
      showed no activation of caspases, surprisingly, all the apoptosis process except
      DNase-gamma activation was observed in U251SP and U251MG cells. Collectively,
      these findings indicate that IFN-beta induced apoptosis in human glioma cells
      through activation of caspase-7 and activation of DNase-gamma. The similar
      activations of caspases were found also in some of the apoptosis resistant cells.
      These findings may help to improve the IFN-beta therapy in near future.

PMID- 15164983
TI  - Loss of 14q chromosome in oligodendroglial and astrocytic tumors.
AB  - Loss of chromosome 14q has been investigated in 142 gliomas. Loss of
      heterozygosity (LOH) at one or more microsatellite has been found in 8/30 grade
      II (27%) and 2/21 grade III (10%) oligodendrogliomas, 3/9 grade II (33%) and 5/15
      grade III (33%) oligoastrocytomas, 0/9 grade II (0%) and 1/7 grade III (14%)
      astrocytomas, 11/51 glioblastomas (22%). Two minimal regions were identified on
      14q21.2-14q24.3 (between D14S288 and D14S74) and 14q31.3-14q32.1 (between D14S74
      and D14S65). Loss of 14q was not correlated to survival, histological grading and
      subtype or other genetic alterations, except for 1p deletions. Taken together,
      these data suggest that LOH14q is an early alteration involving 20% of glioma.

PMID- 15164984
TI  - Interstitial infusion of IL13-PE38QQR in the rat brain stem.
AB  - Interstitial infusion of IL13-PE38QQR, a tumor specific, chimeric cytotoxin, into
      the rat brain stem was performed in an effort to assess safety. Six rats
      underwent stereotaxic cannula placement into the pontine segment of the brain
      stem followed by a 24-h infusion of IL13-PE38QQR (volume of infusion (Vi) 200
      microl) at a concentration of 10 microg/ml. The animals were assessed
      neurologically and then sacrificed either immediately or after 2 weeks. All
      animals tolerated the infusions without exhibiting any neurological changes.
      Postmortem examination of the brains revealed no significant histological changes
      beyond the site of the cannula tract. These findings indicate that
      supratherapeutic concentrations of IL13-PE38QQR administered by interstitial
      infusion into the rat brain stem is well tolerated and may serve as a potential
      therapeutic strategy for children with diffuse pontine gliomas.

PMID- 15164985
TI  - Spheroid preparation from hanging drops: characterization of a model of brain
      tumor invasion.
AB  - BACKGROUND: The use of three-dimensional in vitro models of brain tumor invasion
      has provided a system for reconstructing some of the cellular microenvironments
      present in the tumor mass. While spheroids of murine and human astrocytoma cells
      can be prepared using spinning cultures, spheroid preparation using many cell
      lines is not amenable to this method. We have developed a reproducible system of
      creating implantable spheroids that is applicable to different cell lines, and is
      independent of cell line characteristics. METHODS: For murine and human brain
      tumor cell lines, 20 microl drops containing predetermined cell concentrations
      were suspended from the lids of culture dishes and the resulting aggregates were
      transferred to culture dishes base-coated with agar. The two-dimensional
      aggregates formed three-dimensional spheroids on the non-permissive agar
      substrate, and were then implanted into three-dimensional collagen I gels and the
      invasive activity assessed. The invasive activity of C6 and U251 spheroids
      prepared by hanging drops was compared to spheroids of similar size prepared by
      spinner culture. RESULTS: The hanging drop method produced implantable spheroids
      capable of sustained invasion using all cell lines tested. Most cell lines
      required initial hanging drop cell concentrations of 45,000 cells/drop,
      suspension times of 48, and 72 h on agar. C6 spheroids had the same invasive
      capacity regardless of the model utilized, however U251 spheroids produced by
      hanging drops had significantly increased invasion compared to those prepared by
      spinner culture. Only spheroids prepared by spinner culture showed histological
      evidence of central necrosis. CONCLUSIONS: This model represents a reproducible
      approach to the preparation of implantable spheroids with invasive potential that
      compares with those produced using spinner culture. The use of hanging drops
      broadens the applicability of three-dimensional in vitro assays examining brain
      tumor invasiveness.

PMID- 15164986
TI  - CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk
      between endothelial and tumoral cells.
AB  - CXCL12 (stromal cell-derived factor-1/CXCL12) regulates leukocyte, endothelial
      and hematopoietic precursor migration, bone-marrow myelopoiesis and angiogenesis.
      CXCL12 and its receptor CXCR4 are over-expressed in malignant gliomas, which are
      highly vascularized tumors with a poor prognosis. We studied the expression of
      CXCL12 and CXCR4 in glioma cell lines, endothelial cells, tissue sections and
      endocavitary fluids from patients with gliomas. We then analyzed the
      proliferative and the apoptotic effect of CXCL12 in endothelial cells and glioma
      primary cultures. We observed the release of CXCL12 in supernatants of human
      brain microvascular endothelial cells and at variable levels, in post-surgical
      endocavitary fluids. CXCL12 was expressed in both glioma and endothelial cells as
      assessed by immunostaining of surgical brain sections. CXCR4 was found in cells
      lines and primary cultures from malignant gliomas as well as in endothelial cells
      and was increased by vascular endothelial growth factor and basic fibroblast
      growth factor (bFGF). CXCL12 inhibited bFGF-induced proliferation of endothelial
      cells and increased the survival of endothelial cells. The survival of primary
      cells obtained from glioma specimens was also enhanced in the presence of CXCL12.
      We point out the presence and the release of CXCL12 in tumor microenvironment and
      we observed a modulating effect of CXCL12 on proliferation and survival of both
      endothelial and tumoral cells. Our data support in vivo studies suggesting a role
      in angiogenesis played by CXCL12, which could represent a possible prognostic
      factor.

PMID- 15164987
TI  - Interstitial infusion of carmustine in the rat brain stem with systemic
      administration of O6-benzylguanine.
AB  - Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction
      with systemic administration of O6-benzylguanine (O6-BG) was performed in an
      effort to assess clinical tolerance. A total of 12 rats underwent stereotactic
      cannula placement into the pontine segment of the brain stem. Six of the rats
      underwent a 24-h infusion of BCNU (Volume of infusion [Vi] 200 microl) at its
      maximal concentrated dose (3.3 mg/ml) in 5% dextrose water. Six additional rats
      underwent 24-h infusion of BCNU preceded by an intraperitoneal injection of O6-BG
      at a dose of 50 mg/kg. Serial neurological examinations were performed on all
      animals. Histologic analyses were performed immediately or 2 weeks following
      sacrifice. Postoperatively, there were no neurological changes in any of the
      animals. Postmortem histological examination of the brains showed small pontine
      cavitary lesions (ranging from 20 to 250 microm) containing variable numbers of
      macrophages or neutrophils consistent with an inflammatory response. No changes
      beyond these findings indicated any histological evidence of injury. These
      finding were limited only to the cannula site and no changes beyond region of the
      cannula tract were found. These findings indicate that interstitial infusion of
      BCNU into the brain stem in conjunction with systemic administration of O6-BG is
      safe in a small animal and may serve as a potential investigative strategy for
      children with diffuse pontine gliomas.

PMID- 15164989
TI  - Images in neuro-oncology. Pilocytic astrocytoma.

PMID- 15164988
TI  - Toxicity and cerebrospinal fluid levels of carboplatin chronically infused into
      the brainstem of a primate.
AB  - PURPOSE: Carboplatin was infused into the brainstem of cynomolgus monkeys to
      investigate neurotoxicity and systemic exposures following chronic local
      delivery. METHODS: Infusions at 0.42 microl/h were intended to deliver 0.025 (n =
      2), 0.075 (n = 3), 0.25 (n = 5), and 0.75 (n = 3) mg/kg by day 30. Laboratory
      tests, radiographic measurements, and clinical observations were used to monitor
      toxicity. Blood and cerebrospinal fluid (CSF) were sampled for platinum. RESULTS:
      Lethargy and ataxia were observed after week 4 in the monkeys given 0.075 mg/kg,
      and week 2 in the monkeys given 0.25 mg/kg when the infused doses were
      approximately 250 and 400 microg, respectively. Rapidly progressive neurotoxicity
      with the 0.75 mg/kg dose required termination of the infusions at days 4-10.
      Hematology and chemistry values were unremarkable in all groups. Blood levels of
      platinum remained undetectable in 0.025 and 0.075 mg/kg dose groups. Levels in
      the 0.25 mg/kg group were 3.1 +/- 0.6 microg/l at 2 weeks and 5.2 +/- 0.8
      microg/l at 1 month. The CSF platinum levels varied. Animals in the 0.25 mg/kg
      group had higher CSF levels at 2 weeks (avg. 65 microg/l, range 36-89) compared
      to their 1 month value (avg. 60 microg/l, range 7-170), despite the constant
      infusion. CONCLUSION: Carboplatin can be chronically infused into monkey
      brainstems. Neurotoxicity is the predominant side effect and is dose-dependent.
      Pharmacokinetics of local and systemic delivery are different for carboplatin.
      Further studies are needed to monitor toxicity at higher flow rates and to
      investigate drug binding to abnormal central nervous system (CNS) tissues.

PMID- 15164990
TI  - Malignant intracranial epithelioid hemangioendothelioma presumably originating
      from the lung: case report.
AB  - OBJECTIVE AND IMPORTANCE: Epithelioid hemangioendothelioma (EHE) is a rare
      vascular tumor that presents histological features and biological behavior of low
      grade malignancy. The authors report a case of malignant intracranial EHE, in
      which surgical excisions and additional immuno-chemotherapy were ineffective.
      Emphasis is placed on the histological features of this rare tumor and its
      potential for malignancy. CLINICAL PRESENTATION: A 69-year old male presented
      with paresis of the right arm. Magnetic resonance imaging revealed intracranial
      multiple lesions in the right temporal and parietal and left frontal lobes. Chest
      radiography revealed a mass lesion occupying the lower lobe of the left lung that
      had been followed as old tuberculosis since it had not changed in size for as
      long as 5 years. INTERVENTION: We performed craniotomy and excised tumors.
      Histological examination demonstrated that the excised tumors had the features of
      EHE. Further intracranial recurrence after the excision of the tumors
      necessitated adjuvant treatment with interferon alpha-2b. However, the patient
      continued to deteriorate and died 3 months later. Postmortem study disclosed the
      tumor cells existing in the left lung, pleura, ribs, intercostal tissues and
      diaphragm. Other organs including liver, bone, and skin were free from tumor
      invasion, which indicated that the malignant EHE originated from the left lung
      and metastasized to the brain. CONCLUSION: To the authors knowledge, no case of
      malignant EHE that simultaneously involves the central nervous system and the
      lung has been previously reported. An extensive inspection for involvement of
      other organs is recommended after recognizing an intracranial EHE.

PMID- 15164991
TI  - S-100beta protein--serum levels in children with brain neoplasms and its
      potential as a tumor marker.
AB  - OBJECTIVE: To determine if serum S-100beta levels are elevated in children with
      brain neoplasms and if it can be used as a tumor marker for children with brain
      neoplasms. DESIGN: Prospective cohort study. SETTING: Urban, tertiary care,
      children's teaching hospital. PATIENTS: 136 healthy children and 27 children with
      brain neoplasms. METHODS: Serum levels of S-100beta were measured in 136 healthy
      children to serve as controls and 27 children with brain neoplasms, who underwent
      biopsy or resection of the mass. Patients were then classified into astrocytoma
      or non-astrocytoma groups. MEASUREMENTS AND MAIN RESULTS: The median serum S
      100beta level for the control group was 0.27 mcg/l (range, 0.06-2.6 mcg/l), and
      for the brain neoplasm group was 0.2 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.09).
      There were 13 children with astrocytomas and 14 with non-astrocytomas. The S
      100beta levels for the astrocytoma group was 0.25 mcg/l (range, 0.05-1.1 mcg/l)
      and for the non-astrocytoma group 0.17 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.47).
      CONCLUSIONS: Serum S-100beta levels are not elevated in children with brain
      neoplasms compared to healthy children, nor are they elevated in children with
      astrocytomas compared to non-astrocytomas. The S-100beta protein does not appear
      to be useful as a serum tumor marker in children with brain neoplasms.

PMID- 15164992
TI  - The early effects of radiotherapy on intellectual and cognitive functioning in
      patients with frontal brain tumours: the use of a new neuropsychological
      methodology.
AB  - Investigations of the effects of radiation on neuropsychological functions have
      revealed variable outcomes, ranging from no effect to severe cognitive
      impairment. However, many of the previous studies have relied on retrospective
      data or have been limited by methodological problems. In this study, prospective
      neuropsychological assessments were compared at baseline (after surgery and
      before radiotherapy) and within 4 months of completion of radiotherapy (except
      one case), to examine early-delayed effects of radiation on intellectual and
      cognitive functioning. Sixteen adult patients with either low- or high-grade
      brain tumours, 15 of whom were treated with radiotherapy, were compared with 8
      control participants with nonmalignant brain tumours whom did not undergo
      radiotherapy. All participants had lesions situated mainly in the frontal lobes.
      All groups of patients had evidence of intellectual and cognitive impairment at
      baseline. The low- and high-grade brain tumour groups showed a differential
      pattern of performance following radiotherapy, with the low-grade tumour group's
      performance being more competent on all of the five main neuropsychological
      measures. Their pattern of improvement was very similar to that of the
      nonmalignant brain tumour group who had not undergone radiotherapy. The present
      study provides some preliminary information about the neuropsychological deficits
      associated with primary brain tumours, their severity, and the relationship
      between neuropsychological functioning and brain tumours and radiotherapy.

PMID- 15164993
TI  - Epithelioid hemangioendothelioma of the infundibular-hypothalamic region: case
      report and literature review.
AB  - Epithelioid hemangioendothelioma (EHE) is an uncommon vascular neoplasm. Its
      intracranial occurrence is rare, and the literature review revealed only 23 cases
      (14 adults and 9 children). To our knowledge, this is the first case of EHE
      arising in the infundibular-hypothalamic region. A 53-year-old man presented with
      headaches and loss of libido. Magnetic resonance imaging revealed a supra-sellar
      mass, which homogeneously absorbed the contrast agent. A trans-sphenoidal
      craniotomy and a biopsy were performed. Adjuvant radiotherapy was administered
      due to intolerance to interferon. Epithelioid hemangioendothelioma is a
      hemorrhagic tumor. Total resection is mandatory where possible, otherwise
      radiotherapy seems necessary. The prognosis of intracranial location has not yet
      been well defined, despite the favorable outcome noted in the majority of cases.

PMID- 15164994
TI  - Desferoxamine (DFO)--mediated iron chelation: rationale for a novel approach to
      therapy for brain cancer.
AB  - Iron homeostasis is crucial to normal cell metabolism, and its deficiency or
      excess is associated with numerous disease states. The association of increased
      iron load with cancer may be due to several factors including free radical
      production, reduction of the body's protective mechanism to combat oxidative
      stress, inhibition of immune systems, inhibition of essential nutrient functions,
      facilitation of cancer growth, suppression of antitumor actions of macrophages,
      and lowering of the ratio of T4-T8 positive lymphocytes. Antiproliferative
      effects of desferoxamine (DFO) both in vitro and in vivo are mediated by an
      intracellular pool of iron that is necessary for DNA synthesis rather than
      prevention of iron uptake from transferrin. Several clinical studies have shown
      it to have antitumor activity in the treatment of neuroblastoma, leukemia,
      bladder carcinoma, and hepatocellular carcinoma. Human neural tumor cells are
      susceptible to the effects of DFO. Continued study of DFO is necessary to further
      elucidate its antineoplastic profile and its use as an adjunct to current
      chemotherapy regimens. Given the lack of satisfactory treatment of central
      nervous system neoplasms, DFO could serve as an important tool in the management
      of such cancers.

PMID- 15164995
TI  - Inducing Graves' ophthalmopathy.
AB  - The majority of patients with Graves' disease (GD) have some degree of ocular
      involvement and this requires surgical or medical intervention in about 5% of
      cases. There are autoimmune and inflammatory processes operating in Graves'
      ophthalmopathy (GO), which together induce glycosaminoglycan production, edema
      and adipogenesis resulting in an increase in the volume of the orbital contents.
      GO is a heterogeneous disorder, i.e.: 1) whilst usually associated with
      hyperthyroidism it may occur in euthyroid (and even hypothyroid) patients; 2)
      expansion of orbital tissues may be due to 'big-fat' or 'big muscles'. The
      heterogeneity is further exemplified by the spectrum of protocols which have
      succeeded in inducing aspects of the disease both in animal models and in humans
      including: 1) Production of severe hypothyroidism in guinea pigs by thyroidectomy
      and administration of pituitary extract (TSH); 2) Induction of T cells
      autoreactive to the thyrotropin receptor (TSHR) in mice; 3) Depletion of
      regulatory T cells in humans susceptible to autoimmunity; 4) Modulation of
      adipose tissue metabolism in mice and men. In addition, identical induction
      protocols result in different pathological features depending on the environment,
      e.g. TSHR primed T cells produce thyroiditis and ocular pathology in BALBc mice
      in Brussels but thyroid stimulating antibodies accompanied by elevated thyroxine
      in these animals (from the same supplier) in Cardiff. Thus, experiences in the
      induction of GO have confirmed the polygenic, multifactorial nature of the
      disorder and highlight the importance of careful disease classification to
      promote further progress in understanding.

PMID- 15164996
TI  - TSH receptor expression in orbital tissue and its role in the pathogenesis of
      Graves' ophthalmopathy.
AB  - The TSH receptor (TSHr) is the autoantigen responsible for the hyperthyroidism of
      Graves' disease. Recent studies suggest that this receptor may also be an
      autoimmune target in Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD).
      Its involvement in the pathogenesis of these conditions would help to explain the
      close clinical associations between hyperthyroidism, GO and PTD. TSHr has been
      shown to be present in normal orbital and dermal tissues and evidence supports
      the conviction that expression may be increased in tissues involved in GO and
      PTD. In the setting of Graves' disease, the expression of this antigen in
      connective tissues throughout the body may lead to systemic, subclinical
      connective tissue inflammation. Given this background, local or environmental
      factors such as circulating or local cytokines, gravitational dependency,
      anatomic constraint of the bony orbit, or trauma, may augment clinical disease
      involvement within the orbit and pretibial skin. Alternately, locally enhanced
      expression of this protein at the sites of clinical disease may not be directly
      involved in pathogenesis, but could be secondary to the ongoing process, and
      nonetheless important in disease progression.

PMID- 15164997
TI  - Eye muscle antibodies in Graves' ophthalmopathy: pathogenic or secondary
      epiphenomenon?
AB  - The extra ocular (eye) muscles are one of the principal tissues involved in the
      autoimmune-mediated inflammation of Graves' ophthalmopathy (GO). Several eye
      muscle proteins are targeted by autoantibodies or sensitized T lymphocytes, or
      both, and include: G2s, which is now identified as the terminal 141 amino acids
      of the winged-helix transcription factor FOXP1, the flavoprotein (Fp) subunit of
      the mitochondrial enzyme succinate dehydrogenase, the so-called "64kDa protein",
      a non-tissue specific membrane protein called 1D and the calcium binding protein
      calsequestrin. Of these, antibodies against G2s and Fp are the most sensitive
      markers of eye muscle damage in patients with thyroid autoimmunity even though
      neither antigen is specific to eye muscle and neither antibody is specific to GO.
      However, the recent finding that the calsequestrin gene is 4.7 times more
      expressed in eye muscles than other skeletal muscles suggests that we should
      reconsider the possible role of anti-calsequestrin autoantibodies in
      ophthalmopathy. GO may comprise two main subtypes with different pathogenetic
      mechanisms, namely ocular myopathy in which eye muscle inflammation predominates
      and congestive ophthalmopathy where inflammatory changes occur in the periorbital
      connective tissues in the absence of eye muscle dysfunction. Anti-G2s and anti-Fp
      antibodies are closely associated with the ocular myopathy subtype of GO while
      antibodies targeting type XIII collagen, the only member of the collagen family
      to have a transmembrane domain, are closely linked to congestive ophthalmopathy.
      Since both G2s and Fp are intracellular antigens it is unlikely that either
      antibody causes eye muscle fiber damage in GO, although a role in the later
      stages of the disease when the fiber has released its cellular contents has not
      been excluded. Eye muscle antibodies that are cytotoxic to eye muscle cells in
      antibody-dependent cell-mediated cytotoxicity (ADCC) are more likely to play a
      role in eye muscle fiber damage since they target a putative eye muscle cell
      membrane antigen, the identity of which is currently being investigated. While
      anti-G2s and anti-Fp antibodies are probably secondary to an underlying reaction,
      such as cytotoxic T lymphocyte targeting of an eye muscle membrane antigen that
      has yet to be identified, they are reliable markers of immunologically mediated
      eye muscle fiber damage in patients with Graves' hyperthyroidism. In conclusion,
      while a pathogenic role for eye muscle antibodies has not been excluded, they are
      most likely secondary to cytotoxic T cell reactions in GO and, as such, good
      markers of this autoimmune disease.

PMID- 15164998
TI  - Role of thyroglobulin in the pathogenesis of Graves' ophthalmopathy: the
      hypothesis of Kriss revisited.
AB  - One of the hypothesis to explain the pathogenesis of Graves' ophthalmopathy (GO)
      was formulated by Joseph P. Kriss in the early 1970s. He postulated that the
      initiating event in the pathogenesis of GO is the deposition and accumulation of
      thyroglobulin (Tg) in orbital tissues, followed by an autoimmune reaction against
      Tg. In the last 30 yrs several studies have addressed this hypothesis, through
      various, different experimental approaches, raising results that are both in
      favor and against the possibility that Tg plays a role in the pathogenesis of GO.
      The finding that intact Tg is present in orbital tissues of GO patients supports
      Kriss' hypothesis, although the role of Tg as an autoantigen seems to be
      unlikely, as GO is not significantly associated with serum TgAb and mice
      immunized with Tg do not develop GO. Whether Tg is indeed involved in the
      pathogenesis of GO remains to be established. Our current view is that, provided
      that Tg plays a role, it is unlikely the only factor involved and Tg in orbital
      tissues may rather reinforce or worsen a damage initiated by other mechanisms.

PMID- 15164999
TI  - New understanding of the role of cytokines in the pathogenesis of Graves'
      ophthalmopathy.
AB  - Cytokines play a key role in the development of Graves' ophthalmopathy (GO).
      These molecules are produced in the orbit of GO patients by infiltrating
      inflammatory cells as well as orbital fibroblasts. Locally produced cytokines
      stimulate fibroblast proliferation and their production of glycosaminoglycans,
      which result in accumulation of extracellular matrix and oedema with consequent
      proptosis. In addition to these direct effects, cytokines can modulate the immune
      reaction in GO by increasing major histocompatibility complex (MHC) class II,
      adhesion molecules, CD40, prostaglandin and heat shock protein expression in the
      orbit, thereby having a role in localising and augmenting the inflammatory
      response.

PMID- 15165000
TI  - Novel aspects of orbital fibroblast pathology.
AB  - Orbital fibroblasts exhibit a unique phenotype including exaggerated responses to
      proinflammatory cytokines. We hypothesize that the unusual susceptability of
      these fibroblasts to molecular cues underlies the involvement of the orbit in
      Graves' ophthalmopathy. A number of attributes of orbital fibroblasts are
      reviewed in this article. In addition, we have found IgG circulating in patients
      with Graves' disease that binds and activates the insulin-like growth factor-1
      receptor displayed on fibroblasts from many anatomic regions. Activation of this
      receptor leads to the expression of T-cell chemoattractants. Thus, fibroblast
      activation, and the resulting T-cell trafficking to connective tissue in Graves'
      disease may be systemic. The consequences of lymphocyte-derived cytokine action
      may differ vastly in the orbit and other tissues manifesting clinically obvious
      disease.

PMID- 15165001
TI  - Recent developments in Graves' ophthalmopathy imaging.
AB  - Orbital ultrasound, computed tomography, and magnetic resonance are commonly used
      as imaging techniques to demonstrate pathological changes in ocular adnexa of
      patients with Graves' ophthalmopathy. Low cost, short time of investigation, and
      lack of radiation characterize ultrasound. Nevertheless, a clear differentiation
      regarding disease activity is not possible, nor is the evaluation of orbital
      tissue precise enough. Short investigation time, precise imaging of the orbital
      apex and moderate costs are advantages of tomography. This method delivers a
      significant radiation dose to the lens, which if repeated constitutes a risk for
      cataract development. For this reason, magnetic resonance imaging is preferable,
      particularly if repeated scans are required to assess response to treatment.
      Precise tissue differentiation and lack of ionizing radiation uniquely suit
      magnetic resonance for eye studies. Although sensitive in demonstrating
      interstitial edema within the rectos muscles in active disease, as well as
      providing a good predictive value with respect to immunosuppressive therapy,
      quantitative magnetic resonance imaging is an expensive method and is non
      specific for the orbital changes in ophthalmopathy. Because of a favorable target
      to background ratio, octreoscan carries a high sensitivity and may be regarded as
      a semi-objective tool in the evaluation of patients with Graves' ophthalmopathy,
      both at initial stages as well as during treatment. A positive orbital octreoscan
      indicates a clinically active disease in which immunosuppressive treatment might
      be of therapeutic benefit. However, it is an expensive method with a non
      negligible radiation burden. Also, it is neither specific nor does it offer
      detailed orbital imaging. In summary, in unclear cases of proptosis or recently
      developed diplopia, prior to orbital decompression surgery, or if imaging is
      needed in subjects with ophthalmopathy, magnetic resonance actually is the
      imaging method of choice.

PMID- 15165002
TI  - Effects of Graves' ophthalmopathy on quality of life.
AB  - General health-related quality of life is markedly impaired in patients with
      Graves' ophthalmopathy (GO), and even worse than in patients with other chronic
      conditions like diabetes, emphysema or heart failure. A disease-specific quality
      of-life questionnaire for GO has been developed, the so-called GO-QOL, consisting
      of two subscales: one for visual functioning (8 questions referring to
      limitations due to decreased visual acuity and/or diplopia) and one for
      appearance (8 questions referring to limitations in psychosocial functioning due
      to changes in appearance). The GO-QOL was found to be a valid and reliable
      instrument. A minimal clinically important difference (MCID) in the GO-QOL score
      was derived from data obtained before and after specific eye treatments. Based on
      the patient's opinions, changes of > or = 6 points (minor surgery) or > or = 10
      points (surgical decompression, immunosuppression) are recommended as MCID. It is
      concluded that the GO-QOL is an useful instrument for measuring changes over time
      in visual functioning and appearance of GO patients. The GO-QOL is available in
      six languages, and can be used as a separate outcome measure in clinical studies.

PMID- 15165003
TI  - Relationship between cigarette smoking and Graves' ophthalmopathy.
AB  - Environmental triggers in the development of Graves' disease (GD) have been
      suggested from the very first description of the disease. Since 1987 a number of
      studies from various countries, have assessed the risk for Graves' ophthalmopathy
      (GO) associated with smoking, and found an odds-ratio of approximately 4
      associated with smoking. Smokers have a higher risk for more advanced GO and a
      dose response relation is evident. Temporality is suggested by a few prospective
      studies, as is reversibility since former smokers had a lower risk of developing
      GO than current smokers, even with a comparable lifetime tobacco consumption. In
      view of the biological plausibility of the association (suggested mechanisms
      include tissue hypoxia, modulation of circulating pro- and anti-inflammatory
      cytokines and accentuation of fibroblast HLA-DR expression) it seems that the
      association is, indeed, causal. Treatment effect of GD/GO is also influenced by
      cigarette smoking. It is an independent risk factor for relapse of GD after
      antithyroid drug treatment. Furthermore, it attenuates the effect of orbital
      radiotherapy and high-dose systemic glucocorticoids in GO and causes a higher
      rate of progression of eye disease after radioiodine therapy. The possibility of
      hindering GO or attenuating its course suggests that counselling on smoking
      cessation should be an integral part of the treatment of any patient with GD.

PMID- 15165004
TI  - Novel aspects of immunosuppressive and radiotherapy management of Graves'
      ophthalmopathy.
AB  - Treatment of severe Graves' ophthalmopathy (GO) is a complex therapeutic
      challenge and, in spite of any efforts, about one third of patients are
      disappointed with the outcome of treatment. Glucocorticoids (GC), orbital
      radiotherapy (RT), or a combination of both, are most frequently used for their
      immunosuppressive effects. Novel immunosuppressive treatment procedures (or novel
      modalities of established treatments) are reviewed in the present article. GC has
      recently been used by the i.v. route and this treatment modality has been shown
      to be more effective and better tolerated than the oral route. Promising
      preliminary results have been reported by some authors with somatostatin analogs,
      octreotide and lanreotide. The number of patients treated so far is limited, most
      of the results have been obtained in nonrandomized or uncontrolled studies, and
      comparison with other validated methods of treatment is also needed. Because of
      the pathogenic role of cytokines, cytokine antagonists, currently evaluated in
      other autoimmune diseases, have been tested with positive results also in a small
      series of GO patients. The use of antioxidants might also be envisioned in the
      future, since in vitro studies have shown that oxygen free radicals might be
      involved in GO. Based on the shared antigen(s) theory, total thyroid ablation, by
      removing the bulk of shared antigens(s), might be beneficial for the course of
      GO. New data on recently performed placebo-controlled studies on orbital
      radiotherapy are discussed, together with studies on long-term safety of orbital
      radiotherapy.

PMID- 15165005
TI  - Somatostatin analogs: a new tool for the management of Graves' ophthalmopathy.
AB  - Somatostatin (SM), a peptide inhibiting the release of GH, is present and plays
      an inhibitory role in the regulation of several organ systems in men and other
      species. Various SM analogs (SM-As) have been developed and used in clinical
      practice because the short half-life of SM makes it unsuitable for routine
      treatment. Recently it has been shown that SM-As might be of therapeutic value in
      the treatment of active thyroid ophthalmopathy. So far, 61 patients have been
      treated with octreotide and the results have been published in the literature. It
      was found that in 41 patients the drug had a beneficial effect. Ten patients were
      given lanreotide and 8 of those had a positive response, while 23 patients were
      treated with long-acting release octreotide and 16 improved. The exact mechanism
      of action of SM-As has not yet been fully clarified. One possible mechanism could
      be a direct inhibition of insulin-like growth factor (IGF)-I mediated effects. A
      second mechanism could be an inhibition of the release of lymphokines and
      inflammatory mediators from T-lympocytes. Finally, SM-As may act directly on
      target cells through specific cell surface receptors. With the introduction from
      Novartis of SOM-230, a compound which binds with high affinity to SM-receptors
      (SM-Rs) subtypes 1, 2, 3 and 5, with lower affinity to SM-Rs 4, and which has a
      very favorable T1/2 of nearly 24 h, a much better therapeutic outcome is
      expected. Thus, SM-As may provide a well-tolerated therapeutic alternative to
      corticosteroids. However, prospective placebo-controlled studies with large
      numbers of patients are needed before their role in the treatment of Graves'
      opthalmopathy is definitely established.

PMID- 15165008
TI  - Evidence-based medicine in orthopaedics.
AB  - Evidence-based medicine (EBM) is medicine based on the sum of personal clinical
      experience and clinical studies with the best possible design (preferably, but
      not necessarily, randomised controlled trials or RCTs), while focusing on the
      expectancies of patients and institutions.

PMID- 15165007
TI  - Graves' ophthalmopathy: state of the art and perspectives.
AB  - Graves' ophthalmopathy (GO) is an autoimmune orbital disorder most commonly
      associated with Graves' disease. Recent studies have underscored the role that
      orbital cells, particularly fibroblasts and adipocytes, play in causing the
      increase in orbital content responsible for clinical manifestations of the
      disease. GO seems to be related to autoimmune reactions triggered by autoreactive
      T lymphocytes of thyroid origin, which recognize antigen(s) shared by thyroid and
      orbit. The nature of the antigen (or antigens) involved is not fully understood,
      but TSH receptor is likely to be involved. Cytokines secreted by T lymphocytes,
      macrophages and fibroblasts play an essential role in perpetuating the disease.
      Animal models of GO have been developed, but results have not clarified GO
      pathogenesis yet. Progress in the management of the ophthalmopathy has been very
      limited, and glucocorticoids, orbital radiotherapy and orbital decompression
      remain the mainstays in GO treatment. Novel treatments, such as somatostatin
      analogues, antioxidants, cytokine antagonists are currently under investigation,
      as well as the effects of total thyroid ablation. Cessation of smoking currently
      represents the only form of GO (secondary and tertiary) prevention.

PMID- 15165006
TI  - Relationship between management of hyperthyroidism and course of the
      ophthalmopathy.
AB  - The relationship between treatment for hyperthyroidism and course of Graves'
      ophthalmopathy (GO) has been and still is a matter of debate. Literature often
      presents conflicting data, due to several influencing factors, such as selection
      bias, nonrandomized and uncontrolled or retrospective features of many studies,
      nonstandardized evaluation of ocular changes. However, it seems clear that
      neither antithyroid drug treatment nor thyroidectomy affect the natural course of
      GO, while radioiodine therapy may cause, in about 15% of cases, GO progression.
      The latter is more likely in patients who smoke, have pre-existing GO and more
      severe hyperthyroidism, or whose post-radioiodine hypothyroidism is not promptly
      corrected by L-thyroxine. GO progression after radioiodine therapy can be
      prevented by concomitantly treating patients with glucocorticoids, thus making
      radioiodine therapy a safe procedure also in GO patients. The presence of GO
      should not, therefore, influence the choice of treatment for hyperthyroidism.
      Should antithyroid drug treatment or thyroidectomy be selected for patients with
      mild ophthalmopathy, no treatment for GO is necessary, while a short course of
      moderate doses of glucocorticoids is advised if radioiodine therapy is chosen. In
      patients with severe GO, treatment of hyperthyroidism and management of GO
      proceed independently of each other, and either definitive (radioiodine or
      thyroidectomy) or conservative (antithyroid drugs) treatment for hyperthyroidism
      can be selected while treating GO. The authors' preference goes to the former,
      because it depletes intrathyroidal autoreactive T lymphocytes and removes thyroid
      antigens, which are likely to be involved in the pathogenesis of autoimmune
      reactions of the ophthalmopathy.

PMID- 15165009
TI  - Upper limb flaps for hand reconstruction.
AB  - This article reviews three of the most popular upper limb flaps used in hand
      surgery, namely the posterior interosseous flap, the lateral arm flap and the
      radial forearm flap. An anatomic study performed with the use of eight fresh
      cadavers (sixteen upper limbs) is supported by a wide review of the literature.
      The combined posterior interosseous and lateral arm flap is also discussed. It is
      concluded that these flaps are easily harvested and dependable and in spite of
      any disadvantages their combination should be adequate for the treatment of
      almost any hand injury.

PMID- 15165011
TI  - Recurrent anterior shoulder instability. Results of the glenoid based inferior
      capsular shift.
AB  - A total of forty consecutive patients suffering from recurrent traumatic anterior
      shoulder instability underwent stabilisation with a glenoid based inferior
      capsular shift. The patients were followed up prospectively by an independent
      observer (JM) using the Constant-Murley score and objective evaluation of
      shoulder movement and strength with an isometric dynamometer. The mean follow-up
      period was 50 months (range, 2 to 6.8 years). Three patients (7.5%) suffered a
      repeat, high energy, traumatic dislocation following an early return to sports
      activities. "Cybex" testing documented a minimal average loss of external
      rotation movement (4.4 degrees) and strength (4.3%) with the arm in neutral,
      which was higher with the arm at 90 degrees of abduction (i.e., 13.7 degrees and
      15.6%, respectively). The deficit in internal rotation strength was similarly
      lower in neutral position (2%), when compared to the deficit with the arm at 90
      degrees of abduction (13.5%). There was no measurable loss of internal rotation
      motion. Our study supports the use of a glenoid based inferior capsular shift, as
      there is a low recurrence rate and minimal deficit in shoulder movement and
      strength.

PMID- 15165010
TI  - Relative rates and features of musculoskeletal complications in adult sicklers.
AB  - The purpose of this study was to prospectively look for the relative rates and
      features of musculoskeletal complications in a sample of adult homozygous SS
      sicklers in Yaounde. During a 3-year period, known homozygous SS sicklers aged
      sixteen years or more, with suspicion or evidence of locomotor system disease,
      including leg ulcer, were consecutively investigated through complete medical
      history, clinical examination, full blood count, C-reactive protein, standard
      radiographs of the area of complaint, and, when necessary, CT scan and pus
      analysis. Those patients with no definite diagnosis were excluded. The study
      group comprised 84 patients aged 16 to 51 years (mean age: 22 years), with a
      male/female ratio of 0.75. Four of them (4.5%) were older than 40 years. Thirty
      five (41.6%) presented a total of 50 lesions of aseptic osteonecrosis, which were
      located in the hips in 25 cases (50%), in the lumbar spine in 20 cases (40%), in
      the humeral head in four cases (10%) and in the talar body in one case. The hip
      necrosis was grade I in 6 cases, grade II in four, grade III in 11 and terminal
      in four. Multiple sites of necrosis were observed in six patients. Nineteen
      (22.6%) of the sicklers came on with 36 malleolar ulcers, more frequently in
      males (sex ratio: 5/1) and 28 (78%) located on the medial side. Fifteen sites of
      osteomyelitis were noted in 14 patients (17.8%) and septic arthritis in six (7%).
      Less frequent complications were impingement syndrome, gout osteoarthropathy,
      stress fracture, subtalar fusion, knee osteoarthritis, tendonitis of the anterior
      tibialis, and recurrent dislocation of the patella. All patients were managed
      conventionally, except for advanced aseptic necrosis in which the indication for
      arthroplasty was delayed till the terminal stage. As suggested by another recent
      report from Senegal, efforts should be made to improve the life expectancy of
      sicklers in Sub-Saharan African countries, by acting on education, social and
      medical care. Orthopaedic surgery should focus on reducing the failure rate of
      joint replacement in terminal stages of osteonecrosis and designing core
      decompression trials in early stages.

PMID- 15165012
TI  - Functional outcome following internal fixation of intraarticular fractures of the
      distal humerus (AO type C).
AB  - The aim of this study was to evaluate the functional outcome following internal
      fixation of intraarticular fractures of the distal humerus (AO Type C) with a
      minimum follow-up of two years. A retrospective evaluation with prospective
      clinical review was carried out. Twenty-six consecutive patients with fractures
      of the distal humerus were treated over a 31-month period. Their mean age was 56
      years (range, 18-82). Six patients were not available for final clinical review.
      Analysis of the results were based on the medical records, pre-operative and
      postoperative radiographs of all 26 patients and clinical review of 20 patients
      at a mean follow-up of 35 months (range, 24-48 months). Twenty-six fractures were
      fixed using the AO double column plating techniques. Radiographic evaluation of
      the quality of reduction was carried out using a grading system. Clinical outcome
      was assessed using the Broberg and Morrey functional rating index. Fourteen
      patients (70%) had an excellent or good outcome, five patients (25%) a fair
      outcome and one patient (5%) had a poor result. Three patients (15%) underwent a
      second procedure for hardware removal. The mean arc of flexion was 112 degrees
      (range, 85 to 122). Mean pronation was 75 degrees (range, 60-82) and supination
      was 76 degrees (range, 60-80). No patients had achieved normal grip strength; the
      mean grip strength was 82% (range, 46-90%) compared to the uninjured side.
      Fifteen patients (75%) were able to return to their pre-injury level of
      occupation and activity. Seventeen patients (85%) were satisfied with the final
      outcome. We conclude that internal fixation of intraarticular fractures of the
      distal humerus is an effective procedure with an excellent or good functional
      outcome in most patient age groups. Patients have a high level of satisfaction
      and the majority return to their previous level of activity.

PMID- 15165013
TI  - Functional evaluation of comminuted intra-articular fractures of the distal
      humerus (AO type C). Long term results in twenty-six patients.
AB  - The authors present the results achieved in 26 patients who presented with intra
      articular fractures of the distal humerus (8 AO type C1, 8 C2 and 10 C3) and who
      were operatively treated between 1999 and 2001; they were retrospectively
      evaluated after a mean follow-up period of 70.2 months. There were 12 males and
      14 females with a mean age of 46.1 years. After a standard posterior approach
      with olecranon osteotomy, internal fixation was achieved with unilateral or
      bilateral plates and screws, or isolated screws and/or Kirschner wires. Anterior
      intramuscular transposition of the ulnar nerve was performed in 14 of the
      patients. The results were evaluated using the criteria of Morrey. The results
      were graded as excellent in 6 patients (23.1%), very good in 15 (57.6%) and fair
      in 5 (19.3%). Complications included postoperative ulnar nerve palsy (1), wire
      migration (4), heterotopic ossification (3), infection (2) and material failure
      (2). The overall re-operation rate was 38.4%. The authors conclude that careful
      preoperative planning, transolecranon approach for good visualisation, routine
      ulnar nerve exploration and stable internal fixation facilitating early active
      rehabilitation, remain the gold standard for the treatment of intra-articular
      fractures of the distal humerus.

PMID- 15165014
TI  - Surgical treatment of tennis elbow: percutaneous release of the common extensor
      origin.
AB  - Twenty six patients who had undergone percutaneous release of the common extensor
      tendon for lateral epicondylitis were investigated. Fourteen were female and
      twelve were male. The mean follow-up period was 32 months. Symptoms had been
      present for an average of 8.9 months. Before the surgery, all the patients were
      surgically treated with conservative methods; only those that did not respond to
      conservative methods were surgically treated. The common extensor origin was
      released percutaneously. Pain relief was achieved on average eight weeks after
      surgery. The clinical results were evaluated in terms of pain, activity level and
      patient satisfaction. The results were excellent in twenty-four patients, good in
      one and poor in one. Release of the common extensor origin appears as a
      commendable treatment in patients with lateral epicondylar pain not relieved by
      conservative management.

PMID- 15165016
TI  - Lower limb salvage surgery with MUTARS endoprostheses: 2 to 7 year results.
AB  - The reconstruction of bone defects remains a challenge in orthopaedic oncology.
      Allogenic and autologous bone grafts, as well as megaprostheses are well
      recognised methods for bone reconstruction. Modular, both cemented and
      cementless, endoprosthetic systems have become more popular to bridge defects of
      different sizes. The clinical and radiological results of 50 consecutive patients
      treated with MUTARS endoprostheses between 1995 and 2000 were evaluated in a
      prospective clinical study. The average follow-up was 46 months (25-86 months).
      Clinical evaluation showed good results with an average Enneking-Score of 72% (33
      100%, SD +/- 19). Radiological evaluation showed various patterns of bone
      remodelling including extracortical bone bridging. Early symptomatic loosening
      occurred in 11 cases, necessitating revision surgery. In conclusion, the use of
      the MUTARS Endoprosthesis may be a valuable tool in the treatment of major bone
      defects in the lower limb, if the problems with the first-generation design can
      be solved.

PMID- 15165015
TI  - Systemic effects of bilateral tibial versus bilateral femoral shaft fractures. Is
      there a difference?
AB  - The authors investigated the prevalence and the difference in the severity of
      systemic complications following intramedullary nailing of bilateral tibial and
      femoral shaft fractures. A retrospective chart analysis of 12 consecutive
      patients with bilateral tibial shaft fractures (TF) and 14 patients with
      bilateral femoral shaft fractures (FF) was performed. The incidences of bilateral
      tibial fractures and bilateral femoral shaft fractures were 3.8% and 4.6%
      respectively. The median Injury Severity Score (ISS) in TF group was 13 (9-29)
      compared to 16 (9-34) in the FF group (p = 0.169). The mean resuscitation
      requirements were 4.2 (3-11) litres of colloids and crystalloids and 1.7 (0-10)
      units of blood in the TF group and 10.6 (6-16) litres of colloids and
      crystalloids and 9.2 (5-25) units of blood in the FF group (p = 0.002). In the TF
      group there was 1 death compared to 2 in the FF group. In the TF group, there
      were 2 cases of ARDS, 4 cases of deep sepsis and 3 above knee amputations. In the
      FF group, there were 6 cases of ARDS (p = 0.04), 1 case of deep sepsis and 1
      above knee amputation. Patients with bilateral tibial shaft fractures revealed
      lower ISS, resuscitation requirements, ARDS, associated injuries, and mortality
      when compared to bilateral femoral shaft fractures. This is probably due to the
      anatomical difference in the morphology of the bones, volume of liberated
      intravascular marrow fat, organisation and layout of the venous capillary network
      and severity of associated injuries.

PMID- 15165018
TI  - A novel surgical option for the operative treatment of clubfoot.
AB  - Clubfoot (talipes equinovarus) is a condition well known since the time of
      Hippocrates. Numerous conservative treatments have been introduced for this
      condition; few are still in favour. Conservative treatment was used in our
      department up to the third month of age. The indication for surgery was failure
      to correct or maintain the correction after conservative treatment. We report on
      134 children (206 feet) who had operative treatment for clubfoot in our
      department during the period 1990-1996, using a novel surgical technique based on
      extensive posteromedial release combined with the lateral spread of the "extensor
      forces" of the foot. This new technique has produced excellent results.

PMID- 15165017
TI  - Percutaneous plate fixation of fractures of the distal tibia.
AB  - Minimally invasive plate osteosynthesis (MIPO) of the distal tibia offers several
      theoretical advantages compared to classic open reduction and internal fixation.
      A mechanically stable fracture-bridging osteosynthesis can be obtained without
      significant dissection and surgical trauma to the bone and surrounding soft
      tissues. In this retrospective study we looked at the results and complications
      in ten consecutive patients treated with percutaneous plating for fractures of
      the distal tibia and plafond with a minimum follow-up period of one year. No
      significant soft tissue problems occurred. The need for bone grafting should be
      carefully evaluated in every case as we encountered two delayed unions. All
      fractures healed within one year; there was no fracture malunion. The use of
      indirect reduction techniques and small incisions to insert hardware is
      technically more demanding and requires strict radioscopic control throughout the
      procedure, but it considerably decreases surgical trauma to the soft tissues.

PMID- 15165019
TI  - The spacer block technique in osteomyelitis of the phalangeal bones of the hand.
AB  - The authors report a case of an open mallet injury with a traumatic arthrotomy
      which was complicated with a destructive infection involving both the middle and
      distal phalanges of a ring digit and which was treated with two-stage
      reconstructive surgery with good results. In the first stage, after the
      osteomyelitic portion of adjacent phalangeal bones were excised en bloc, the dead
      space was filled by means of an antibiotic-impregnated cement spacer. In the
      second stage, an autogenous corticocancellous bone graft from the iliac crest was
      secured into the defect with a intramedullary Herbert scaphoid screw.

PMID- 15165020
TI  - Simple bone cysts of the proximal humerus complicated with growth arrest.
AB  - A simple bone cyst of the proximal humeral metaphysis was found to cause growth
      disturbance with shortening and deformity in four patients. All had one
      pathological fracture. Three of them were treated with cortisone injections; the
      fourth patient, who presented an erosion of the physis, was treated with saline
      solution irrigation. Four hypotheses about the aetiology of growth arrest in the
      evolution of this benign lesion, are discussed: iatrogenic lesion of the physis,
      growth plate involvement by fracture, cortisone injection, and increased cyst
      pressure leading to erosion and even perforation of the growth plate.

PMID- 15165021
TI  - Bilateral pisiform-hamate coalition causing carpal tunnel syndrome and tendon
      attrition. A case report.
AB  - Congenital coalition of pisiform and hamate is rare and had been considered
      asymptomatic in the first reports. The authors report a case of bilateral
      pisiform-hamate coalition in a young patient, causing symptoms of median nerve
      compression in the carpal tunnel and attritional changes on digital flexor
      tendons. This type of coalition had not previously been related to such symptoms.
      Additionally, the morphology of the coalition on the right side is unique among
      published cases. Surgical treatment with bilateral excision of the coalition
      resulted in the resolution of symptoms.

PMID- 15165023
TI  - Hair-thread tourniquet syndrome. A case report.
AB  - The authors report the case of a 3-month-old boy with hair-thread tourniquet
      syndrome, seen just distal to the MP joint on the right fourth toe. The patient
      was brought to the hospital with a history of irritability and weeping. On
      examination there was swelling, ecchymosis and a hair fibre was found wrapped
      around his right fourth toe. After the hair fibre was removed there was a fast
      healing period and no signs of tissue necrosis were seen.

PMID- 15165022
TI  - Occult fracture of the trapezoid bone: a report on two cases.
AB  - The authors report two cases of isolated, undisplaced, fractures of the trapezoid
      bone. Because of its well-protected position in the wrist, traumatic lesions of
      the trapezoid bone are rare. Dislocation of the trapezoid has been reported in 30
      patients; fractures are seen even less frequently and usually go with dorsal
      displacement. To our knowledge and based on a Medline literature review, only two
      cases of acute and isolated, undisplaced or minimally displaced fractures of the
      trapezoid have been previously described. We believe that the lesion has often
      been missed in the past and modern diagnostic tools will make its diagnosis far
      more frequent.

PMID- 15165024
TI  - Synovial chondromatosis of the hip: a case report and clinicopathologic study.
AB  - Primary synovial chondromatosis (PSC) is a rare, usually monoarticular disorder
      of synovial joints. PSC is characterised by the formation of osteocartilaginous
      nodules in the synovial connective tissue. We report the case of a 32-year-old
      male with PSC of the left hip. At clinical examination abduction of the left hip
      was limited and rotation was painful. Ultrasound examination of the hip revealed
      joint effusion and multiple hyperechogenic foci due to distal acoustic shadowing.
      Plain radiographs showed a slight soft tissue swelling around the femoral neck
      and multiple round or ovoid calcifications of a uniform size. MRI revealed a
      large joint effusion with multiple small filling defects. Open total synovectomy
      was performed after dislocation of the femoral head. The diagnosis of PSC was
      confirmed by histological examination of the excised material. The majority of
      cells failed to exhibit any staining for cerb B-2 and ki-67. None of the sections
      showed more than 5% labelling for DNA-fragmentation proven by terminal
      deoxytransferase-mediated dUTD nick-end labeling (TUNEL), and all were completely
      non-reactive for p53 as well. In conclusion, immunohistochemical analysis
      suggests that in this case PSC originated from metaplasia and not from a
      proliferative process. After two years, the patient was free of symptoms and
      radiological control did not show evidence of recurrence or femoral head
      necrosis. Physical findings, diagnosis, histological features and management of
      PSC are discussed.

PMID- 15165026
TI  - Prostaglandins & other lipid mediators: a new phase, a new team.

PMID- 15165025
TI  - Concomitant alar and apical ligament avulsion in atlanto-axial rotatory fixation.
      Case report and review of the literature.
AB  - The authors report a case of Fielding type II acute atlanto-axial rotatory
      fixation (AARF). The CT scan with coronal reconstruction showed an avulsion of
      the apical and right alar ligament. These findings are exceptionally reported in
      the literature, especially concerning the apical ligament which might be a
      stabiliser in flexion and extension of the occipitocervical joint.

PMID- 15165027
TI  - Peter Ramwell, scientist and editor: a tribute.

PMID- 15165028
TI  - Can endogenous gaseous messengers control mitochondrial biogenesis in mammalian
      cells?
AB  - Mitochondria have been identified as the site of oxidative energy metabolism and
      of numerous biosynthetic and degradative reactions, which depend on a distinctive
      mitochondrial structure, with different enzymes and reactions localised in
      discrete membranes and aqueous compartments. Synthesis and import of
      mitochondrial components are required for mitochondrial proliferation, but rather
      than producing new organelles, these processes may facilitate the growth of
      preexisting mitochondria. Recent evidence indicates that these events are
      regulated in a complex way by several agonists and environmental conditions,
      through activation of specific transcription factors and signaling pathways. Some
      of these are now being elucidated. Generation of nitric oxide (NO) appears to be
      a novel player in this scenario, possibly acting as a unifying molecular switch
      to trigger the whole process of the mitochondrial biogenesis.

PMID- 15165029
TI  - Functional characterization of sphingosine 1-phosphate receptor agonist in human
      endothelial cells.
AB  - Sphingosine 1-phosphate (S1P) is a pleiotropic lysophospholipid mediator involved
      in many cellular responses, including transient calcium mobilization, activation
      of MAP kinase signaling, inhibition of adenylyl cyclase and increased cell
      migration. S1P has been shown to be an effective activator of vascular
      endothelial cells via the interaction with cell surface G protein-coupled
      receptors (GPCRs), namely S1P-R (formerly EDG-R). The potent immunomodulator,
      FTY720, is phosphorylated by sphingosine kinase (SK) to FTY720-P. Recently it was
      shown that FTY720-P, not FTY720, can bind to four out of five of the S1P-R. In
      the present study, we evaluated the effects of FTY720, FTY720-P, and analogues of
      FTY720-P: an active (R)-enantiomer [AFD(R)] and an inactive (S)-enantiomer
      [AFD(S)], on endothelial cell functions. Treatment of HUVEC with FTY720-P, but
      not FTY720, lead to a robust transient increase in calcium mobilization, detected
      using the fluorometric imaging plate reader (FLIPR) assay. Additionally, only the
      phosphorylated derivative (FTY720-P) stimulated MAPK activation. We also observed
      complementary activities of S1P and FTY720-P in an established in vitro
      endothelial morphogenesis (Matrigel tube formation) assay and an in vitro
      endothelial cell migration assay. Using a potent inhibitor of sphingosine kinase,
      N,N-dimethylsphingosine (DMS), FTY720's effects were inhibited in the migration
      assay, suggesting that FTY720-P is the active mediator. The effects of FTY720-P
      in these assays were inhibited by pre-treatment with PTx (pertussis toxin),
      indicating the requirement of a Gi-coupled S1P receptor. These findings suggest
      that agonist of S1P-R are able to regulate important endothelial cell properties,
      which may lead to a greater insight into vascular functions.

PMID- 15165030
TI  - A nomenclature system for isofurans.
AB  - Recently, the isolation of a new class of human arachidonic acid oxidation
      products, the isofurans, was reported. These are produced in vivo by a free
      radical mechanism independent of the cyclooxygenase enzymes. Because these
      compounds are tetrahydrofuran derivatives that are related biosynthetically to
      the isoprostanes, they were termed isofurans. There are eight different isofuran
      regioisomers, each of which can exist as 16 racemic diastereomers. Thus, 256
      enantiomerically-pure isofurans can be formed. These molecules are of interest as
      measurement of isofurans provides a sensitive index of free-radical induced lipid
      peroxidation in vivo under conditions of elevated oxygen tension. They also, in
      analogy to isoprostanes, may have potent biological activity. To explore this,
      the chemical synthesis of the IsoFs has been initiated. As a result, there is a
      need for a systematic nomenclature for this class of natural products. A facile
      system that will allow the ready differentiation of each of the isomeric
      structures comprising the family of isofurans is presented.

PMID- 15165031
TI  - Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in
      pancreatic cancer.
AB  - Despite recognition of the devastating malignant potential of the pancreatic
      ductal cancer, the exact pathophysiological events contributing to tumor growth
      remain to be elucidated. Expression levels of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase (COX)-2 were found to be frequently elevated in several
      types of human cancer and have also been directly linked to carcinogenesis. The
      purpose of this study was to determine the expression of COX-1, COX-2 and iNOS in
      human pancreatic cancer and matched normal adjacent tissue by the Western blot
      assay. Marked COX-2 expression was observed in cancer tissue compared with the
      normal surrounding tissue. The iNOS protein was markedly expressed only in
      pancreatic cancer while the expression of COX-1 was similar in both normal and
      cancerous tissue. Our findings indicate that COX-2 up-regulation and the
      expression of iNOS in pancreatic cancer, not seen in normal tissue, may play a
      role in the pathogenesis of human pancreatic adenocarcinomas. These observations
      suggest that COX-2 and iNOS may be a target for prevention or treatment of
      pancreatic carcinomas.

PMID- 15165032
TI  - Metabolism of anandamide in cerebral microvascular endothelial cells.
AB  - Anandamide (N-arachidonoylethanolamine, AEA), an endogenous cannabinoid receptor
      agonist, causes potent vasodilation in the cerebral circulation through an
      endothelial-dependent or -independent mechanism. We have investigated the
      processing of [3H]AEA in cultured mouse cerebral microvascular endothelial cells
      (MEC) in order to better understand its mechanism of action in the cerebral
      vasculature. These cells took up anandamide very quickly, reaching a maximum
      value in 5 min and remaining at that level for at least 8 h. Analysis of the cell
      lipids demonstrated that, in addition to free anandamide, radioactivity was
      incorporated into phosphatidylcholine (PC), phosphatidylinositol (PI), and
      phosphatidylethanolamine (PE) in a time-dependent manner. Analysis of the
      hydrolyzed cell lipids indicated that anandamide was converted to arachidonic
      acid, a process that was inhibited by the selective fatty acid amide hydrolase
      inhibitor oleyl trifluoromethyl ketone (OTMK). Phospholipase A2 (PLA2) hydrolysis
      of the PC, PI, and PE fractions indicated that the arachidonic acid formed from
      anandamide was esterified predominately into sn-2 position of the endothelial
      phospholipids. Furthermore, anandamide and arachidonic acid were released when
      the cells were incubated with A23187. These results suggest that the biological
      activity of anandamide might be regulated by its rapid uptake and calcium
      dependent release in endothelial cells, and conversion of anandamide to
      arachidonic acid might serve as an inactivation process in the cerebral
      microcirculation.

PMID- 15165033
TI  - Effects of platelet-activating factor and thromboxane A2 on isolated perfused
      guinea pig liver.
AB  - Lipid mediators, thromboxane A2 (TxA2) and platelet-activating factor (PAF), are
      potent vasoconstrictors, and have been implicated as mediators of liver diseases,
      such as ischemic-reperfusion injury. We determined the effects of a TxA2 analogue
      (U-46619) and PAF on the vascular resistance distribution and liver weight (wt)
      in isolated guinea pig livers perfused with blood via the portal vein. The
      sinusoidal pressure was measured by the double occlusion pressure (P(do)), and
      was used to determine the pre- (R(pre)) and post-sinusoidal (R(post))
      resistances. U-46619 and PAF concentration-dependently increased the hepatic
      total vascular resistance (R(t)). The minimum concentration at which significant
      vasoconstriction occurs was 0.001 microM for PAF and 0.1 microM for U-46619.
      Moreover, the concentration of U-46619 required to increase R(t) to the same
      magnitude is 100 times higher than PAF. Thus, the responsiveness to PAF was
      greater than that to U-46619. Both agents increased predominantly R(pre) over
      R(post). U-46619 caused a sustained liver weight loss. In contrast, PAF also
      caused liver weight loss at lower concentrations, but it produced liver weight
      gain at higher concentrations (2.5 +/- 0.3 per 10g liver weight at 1 microM PAF),
      which was caused by substantial post-sinusoidal constriction and increased P(do).
      In conclusion, both TxA2 and PAF contract predominantly the pre-sinusoidal veins.
      TxA2 causes liver weight loss, while PAF at high concentrations increases liver
      weight due to substantial post-sinusoidal constriction in isolated guinea pig
      livers.

PMID- 15165034
TI  - Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and
      CRTH2 in human nasal mucosa.
AB  - BACKGROUND: Prostaglandin D2 (PGD2) is released from mast cells during the
      allergic response. OBJECTIVE: Since PGD2 has been shown to induce nasal
      congestion in humans, we investigated the distribution of hematopoietic
      prostaglandin D synthase (PGDS) and the two PGD2 receptors, DP and CRTH2 in human
      nasal mucosa from healthy subjects and subjects suffering from polyposis, a
      severe form of chronic rhinosinusitis. METHODS: DP mRNA expression was detected
      by in situ hybridization while PGDS, CRTH2 and various leukocyte markers
      expression were revealed by immunohistochemistry. RESULTS: In the normal mucosa,
      PGDS was only detected in few resident mast cells while CRTH2 was undetectable.
      In contrast, DP receptor mRNA was detected in epithelial goblet cells, serous
      glands and in the vasculature. In the nasal mucosa of subjects suffering from
      polyposis: (1) PGDS was detected in mast cells and other large infiltrating
      inflammatory cells, (2) both DP mRNA and CRTH2 were detected in eosinophils and
      (3) CRTH2 was detected on a subset of infiltrating T cells. Although DP mRNA
      could not be detected in the T cells invading the nasal mucosa, it was found to
      be expressed in the T cells present in the lymph node and the thymus from normal
      individuals. CONCLUSION: This study indicates that cells capable of producing
      PGD2 are present in the nasal mucosa and that both PGD2 receptors, DP and CRTH2,
      might play a role in inflammatory disease of the upper airways.

PMID- 15165035
TI  - Quantitative liquid chromatography-tandem mass spectrometric analysis of 11
      dehydro TXB2 in urine.
AB  - A simple and selective determination method of 11-dehydrothromboxane B2 (11
      dehydroTXB2), which is urinary metabolite of TXA2, has been developed employing
      liquid chromatography-tandem mass spectrometry (LC-MS-MS). 11-DehydroTXB2 and its
      deuterium-labeled analogue as an internal standard were extracted from urine by
      simple solid-phase extraction (SPE). These compounds were analyzed using LC-MS-MS
      in the selected reaction monitoring (SRM) mode, by monitoring the transitions
      from m/z 367 to m/z 161 for 11-dehydroTXB2 and from m/z 371 to m/z 165 for its
      internal standard. A good linear response over the range 50 pg-10 ng per tube was
      demonstrated. The values determined by LC-MS-MS were well validated and closely
      corresponded to the values determined by gas chromatography-mass spectrometry (GC
      MS). The mean concentration of 11-dehydroTXB2 in urine of healthy adults was 635
      +/- 427 pg/mg creatinine (mean +/- S.D., n = 13). This simple, accurate and
      selective determination method described in this study should greatly aid in
      evaluating the role of TXA2 in vivo.

PMID- 15165036
TI  - 15-LOX-1 inhibits p21 (Cip/WAF 1) expression by enhancing MEK-ERK 1/2 signaling
      in colon carcinoma cells.
AB  - Currently, some controversy exists regarding the precise role of 15-lipoxygenase
      1 (15-LOX-1) in colorectal carcinogenesis and other aspects of cancer biology.
      The aim of this study was to evaluate the effect of 15-LOX-1 on p21 (Cip/WAF 1)
      expression and growth regulation in human colon carcinoma cells. The effect of 13
      S-hydroxyoctadecadienoic acid (HODE), a product of 15-LOX-1, on p21 (Cip/WAF 1)
      expression was evaluated in Caco-2 cells treated with sodium butyrate (NaBT)
      and/or nordihydroguaiarectic acid (NDGA), a LOX inhibitor. The effect of
      transfecting HCT-116 cells with 15-LOX-1 was also examined. NaBT-induced p21
      (Cip/WAF 1) expression was enhanced by treatment with NDGA and 13-S-HODE reversed
      NaBT-induced p21 (Cip/WAF 1) expression in Caco-2 cells. Overexpression of 15-LOX
      1 induced extracellular signal-related kinase (ERK) 1/2 phosphorylation,
      decreased p21 (Cip/WAF 1) expression, and increased HCT-116 cell growth.
      Treatment with NDGA decreased ERK 1/2 phosphorylation, and increased p21 (Cip/WAF
      1) expression in 15-LOX-1 overexpressing HCT-116 cells. Our experimental results
      support the hypothesis that 15-LOX-1 may have "pro-neoplastic" effects during the
      development of colorectal cancer.

PMID- 15165037
TI  - Application of a TCA-precipitation method for the determination of 1-alkyl-sn
      glycero-3-phosphate: Acetyl-CoA acetyltransferase in human renal tissue.
AB  - The activity of 1-alkyl-sn-glycero-3-phosphate:Acetyl-CoA acetyltransferase,
      which catalyses the first step of the de novo biosynthesis of PAF, was determined
      and characterised in cortical and medullary human renal tissues. A novel thin
      layer chromatographic system as well as a trichloroacetic acid precipitation
      method, were utilised in order to determine the enzyme's activity. The
      acetyltransferase activity was associated with the membranous fractions of the
      renal tissue, it showed an optimum pH of 8.4 and it had a bell-shaped dependence
      on BSA concentration. One or more disulphide bonds were necessary for the action
      of acetyltransferase while the enzyme seemed to be independent from divalent
      cations. Two assay products were extracted from the incubation mixture namely
      alkylacetylphosphatidic acid, produced by the acetylating action of the
      acetyltransferase on alkyllyso-phosphatidic acid and alkylacetyl-glycerol, which
      is produced by the action of a phosphohydrolase on alkylacetylphosphatidic acid.
      The presence of NaF in the assay mixture resulted to a decreased degradation of
      alkylacetylphosphatidic acid, as well as to an increased overall product
      formation. Cortical and medullary acetyltransferases share similar biochemical
      properties and there is no statistical difference between the two activities.

PMID- 15165038
TI  - Constitutive expression of the S1P1 receptor in adult tissues.
AB  - S1P1 (also known as EDG-1) is a G-protein coupled receptor for the bioactive
      lipid, sphingosine-1-phosphate (S1P). Activation of S1P1 receptor in endothelial
      cells induces diverse cellular effects, including cell proliferation, survival,
      migration and morphogenesis. Recent in vivo studies showed that the S1P1 receptor
      is required in vascular maturation during development. While a number of studies
      reported a functional role of S1P1 in vascular system and the presence of S1P1
      transcripts in various mouse organs, tissue distribution of S1P1 has not been
      fully defined. In this study, we determined the expression pattern of S1P1 by
      beta-galactosidase reporter gene expression, which is knocked into the S1P1
      locus. We show that S1P1 is widely expressed in various cell types of adult mouse
      tissues, suggesting a regulatory role of this receptor in numerous physiological
      processes in both vascular and non-vascular tissues.

PMID- 15165039
TI  - Purification, characterization, and immunolocalization of a thioredoxin reductase
      from adult Fasciola hepatica.
AB  - Thioredoxin reductase (TrxR), an enzyme belonging to the flavoprotein family of
      pyridine nucleotide-disulfide oxidoreductases, was isolated from the deoxycholate
      soluble extract of the common liver fluke, Fasciola hepatica. Purification to
      homogeneity of the 60-kDa enzyme from the adult worm was achieved by a
      combination of ammonium sulfate fractionation, anion exchange, and affinity
      chromatography on 2',5'-adenosine diphosphate-Sepharose. Using the 5,5'
      dithiobis(2-nitrobenzoic acid) assay, the purified TrxR showed a specific
      activity of 7,117 U min(-1) mg(-1). The enzyme activity was completely inhibited
      by the presence of the gold compound aurothioglucose (IC50 = 120 nm), indicating
      that F. hepatica TrxR is a selenoenzyme. Also, the enzyme was capable of reducing
      disulfide bonds in insulin and was activated by the presence of the reduced form
      of flavin adenine dinucleotide, properties shared with mammalian TrxRs.
      Furthermore, the isolated enzyme showed very low glutaredoxin (Grx) activity
      (0.47 U mg(-1)), but no glutathione reductase activity was detected. Affinity
      purified IgGs (20 microg ml(-1)) from the antisera produced against the purified
      TrxR inhibited its activity about 80% with respect to the control. The enzyme was
      immunolocalized in cells located within the parenchyma and in the testes, but it
      was not found in the tegument of the adult fluke.

PMID- 15165040
TI  - Cryptosporidium parvum attachment to and internalization by human biliary
      epithelia in vitro: a morphologic study.
AB  - To explore the mechanisms by which Cryptosporidium parvum infects epithelial
      cells, we performed a detailed morphological study by serial electron microscopy
      to assess attachment to and internalization of biliary epithelial cells by C.
      parvum in an in vitro model of human biliary cryptosporidiosis. When C. parvum
      sporozoites initially attach to the host cell membrane, the rhoptry of the
      sporozoite extends to the attachment site; both micronemes and dense granules are
      recruited to the apical complex region of the attached parasite. During
      internalization, numerous vacuoles covered by the parasite's plasma membrane are
      formed and cluster together to establish a preparasitophorous vacuole. This
      preparasitophorous vacuole comes in contact with host cell membrane to form a
      host cell-parasite membrane interface, beneath which an electron-dense band
      begins to appear within the host cell cytoplasm. Simultaneously, host cells
      display membrane protrusion along the edge of the host cell-parasite membrane
      interface, resulting in the formation of a mature parasitophorous vacuole that
      completely covers the parasite. During internalization, vacuole-like structures
      appear in the apical complex region of the attached sporozoite, which bud out
      into host cells. A tunnel directly connecting the parasite to the host cell
      cytoplasm forms during internalization and remains when the parasite is totally
      internalized. Immunoelectron microscopy showed that sporozoite-associated
      proteins were localized along the dense band and at the parasitophorous vacuole
      membrane. These morphological observations provide evidence that secretion of
      parasite apical organelles and protrusion of host cell membrane play an important
      role in the attachment and internalization of host epithelial cells by C. parvum.

PMID- 15165041
TI  - Ligophorus pilengas n. sp. (Monogenea: Ancyrocephalidae) from the introduced So
      iuy mullet, Mugil soiuy (Teleostei: Mugilidae), in the Sea of Azov and the Black
      Sea.
AB  - The monogenean Ligophorus chabaudi was originally described on the gills of the
      flathead mullet, Mugil cephalus, and was subsequently reported on the So-iuy
      mullet, Mugil soiuy. However, the morphology of sclerotized parts and
      multivariate statistical analyses suggest that the form from the So-iuy mullet
      represents a new species. This study provides a description of the new species
      Ligophorus pilengas n. sp. and provides additional morphological data concerning
      the morphology of the ventral bar that might be useful for the diagnosis of
      Ligophorus. Ligophorus pilengas n. sp. is the second species of Ligophorus
      reported on the So-iuy mullet. Zoogeographical records indicate that L. pilengas
      n. sp. was probably introduced to the Black Sea and the Sea of Azov from the
      western Pacific Ocean together with its host.

PMID- 15165042
TI  - Effect, distribution, and prevalence of Glugea stephani (Microspora) in winter
      flounder (Pleuronectes americanus) living near two pulp and paper mills in
      Newfoundland.
AB  - A study was conducted to determine the effects, geographical distribution, and
      prevalence of a microsporan parasite, Glugea stephani, in winter flounder
      (Pleuronectes americanus) in Newfoundland. Fish were captured by SCUBA divers in
      several coastal areas, including 2 embayments where pulp and paper mill effluent
      was discharged, as well as a number of pristine sites. Fish health was assessed
      by comparing histological profiles, condition factors (K), organosomatic indices
      and blood values between infected and uninfected samples. Multifocal xenomas of
      G. stephani were observed in several organs of fish taken near contaminated
      sites, whereas infected samples captured at a pristine site harbored the cysts
      only in the wall of the digestive tract. Proliferative inflammation, granuloma
      formation, and focal necrosis were associated with the infection primarily in the
      liver and kidney. Condition factors and blood values were lower and ovarian
      development inhibited or delayed in infected flounder. The multifocal infection
      occurred only in flounder in 2 embayments in western Newfoundland where pulp and
      paper mill effluent was discharged. Prevalence varied seasonally, with a peak in
      autumn and a low in spring. It is likely that the multifocal infection was
      associated with immunodepression after exposure to the contaminant.

PMID- 15165043
TI  - Livestock trade history, geography, and parasite strains: the mitochondrial
      genetic structure of Echinococcus granulosus in Argentina.
AB  - A sample of 114 isolates of Echinococcus granulosus (Cestoda: Taeniidae)
      collected from different host species and sites in Argentina has been sequenced
      for 391 bp from the mitochondrial cytochrome c oxidase subunit I gene to analyze
      genetic variability and population structure. Nine different haplotypes were
      identified, 5 of which correspond to already characterized strains. Analysis of
      molecular variance and nested clade analysis of the distribution of haplotypes
      among localities within 3 main geographic regions indicate that geographic
      differentiation accounts for the overall pattern of genetic variability in E.
      granulosus populations. Significant geographic differentiation is also present
      when the sheep strain alone is considered. Our results suggest that geographic
      patterns are not due to actual restricted gene flow between regions but are
      rather a consequence of past history, probably related to the time and origin of
      livestock introduction in Argentina.

PMID- 15165044
TI  - Life cycle and paratenesis of American gordiids (Nematomorpha: Gordiida).
AB  - To complete their life cycle, gordiids must make a transition from aquatic to
      terrestrial environments. However, epibenthic aquatic larvae and their
      terrestrial definitive hosts do not overlap in habitat. This has led many
      investigators to suggest that infections are acquired through the ingestion of
      insects, which become infected as aquatic larvae with gordiid cysts and
      subsequently carry gordiids to land. This proposed life cycle was experimentally
      tested using 3 common American species of gordiids: Gordius robustus, Paragordius
      varius, and Chordodes morgani. Cysts of all 3 species survived the metamorphosis
      of Tanytarsus sp., a midge. Subsequent infection trials of definitive hosts with
      cysts from imagos show that cysts surviving the metamorphosis of insects remained
      viable and free of host internal defense reaction. Data from naturally infected
      mayflies, Callibaetus sp., show that encystment and survival of gordiids within
      aquatic insects occur in nature. Paratenesis between paratenic hosts was also
      shown to be possible in these 3 species. This latter finding appears to indicate
      that cysts formed in spurious paratenic hosts may not be lost but may eventually
      transfer to normal paratenic hosts.

PMID- 15165045
TI  - Establishment of adult Parelaphostrongylus tenuis, patent infections, and
      acquired immunity after experimental infection of white-tailed deer (Odocoileus
      virginianus) and red deer (Cervus elaphus elaphus).
AB  - Experimental Parelaphostrongylus tenuis infections were established in white
      tailed deer (Odocoileus virginianus) and an atypical host, red deer (Cervus
      elaphus elaphus). Groups of deer were fed 10, 25, or 100 third-stage larvae (L3)
      of P. tenuis and received a single equivalent challenge exposure at varying
      intervals. Infections were monitored up to 6 yr in white-tailed deer and up to
      2.8 yr in red deer. The prepatent period in white-tailed deer varied from 91 to
      1,072 days (381 +/- 374) and in red deer from 105 to 358 days (167 +/- 77). Adult
      worms lived for up to 6 yr in white-tailed deer. Although most had patent
      infections until necropsy, latent periods were observed regardless of season.
      Adult worms lived for up to 2.8 yr in red deer, and patent infections persisted
      for 20-363 days (152 +/- 106). Patent infections were correlated with the
      presence of adult worms in blood vessels and sinuses of both deer species. Worms
      were restricted to the subdural space in all deer with latent and occult
      infections. Adult worm recovery in white-tailed deer fed 10 or 25 L3 corresponded
      to the mean intensities reported in natural infections of white-tailed deer
      Recovery from deer fed 100 L3 was not typical of natural infection intensities.
      Adult P. tenuis established in all groups of red deer, but neurologic disease was
      restricted to animals fed 100 L3. Acute neurologic disease was associated with
      subdural hemorrhage and occurred at 11 mo postinfection in 2 red deer. The
      absence of postchallenge patent periods and the persistence of occult infections
      indicated that challenge exposures did not establish. These data indicate that
      acquired immunity to P. tenuis was established by 6 mo postinfection in both
      white-tailed and red deer. Latent periods in white-tailed deer and latent
      infections in red deer reinforce the need for a reliable diagnostic assay.

PMID- 15165047
TI  - Helminth parasites of the tropical gar, Atractosteus tropicus Gill, from Tabasco,
      Mexico.
AB  - A total of 8 helminth species were recorded in an examination of 43 tropical gar,
      Atractosteus tropicus Gill, collected at the Pantanos de Centla Biosphere
      Reserve, Tabasco, Mexico. The parasite species included 1 adult trematode, 3
      metacercariae, 1 cestode, 1 adult nematode, and 2 nematode larvae. Six of these 8
      species were rare, with low prevalence (< 17%) and abundance (< 1.0 helminths per
      examined fish). The larvae of Contracaecum sp. were the most abundant in the
      sample, constituting 60% of the total helminths (64% prevalence, 3.8 +/- 5.2
      abundance), followed by the cestode Proteocephalus singularis, constituting 18%
      of the worms (30.5% prevalence, 1.1 +/- 3.0 abundance). Species richness,
      individual parasite abundance, and diversity were low in the infracommunities.
      The recording of 3 specialist species in the tropical gar confirms that the
      helminth fauna of gar has an appreciable degree of specificity. This study
      indicates the importance of ecological determinants of richness in helminth
      communities of the tropical gar.

PMID- 15165046
TI  - Experimental Toxoplasma gondii infection in grey seals (Halichoerus grypus).
AB  - Laboratory-reared animals were used to assess the susceptibility of seals
      (Halichoerus grypus) to Toxoplasma gondii infection. Four seals were each orally
      inoculated with 100 or 10,000 oocysts of T. gondii (VEG strain), and another 4
      seals served as negative controls. Occasionally, mild behavioral changes were
      observed in all inoculated seals but not in control animals. A modified
      agglutination test revealed the presence of antibodies to T. gondii in sera
      collected from inoculated seals and mice inoculated as controls. No evidence of
      the parasite was found on an extensive histological examination of seal tissues,
      and immunohistochemical staining of tissue sections from inoculated seals
      revealed a single tissue cyst in only 1 seal. Control mice inoculated with 10
      oocysts from the same inoculum given to seals became serologically and
      histologically positive for T. gondii. Cats that were fed brain or muscle tissue
      collected from inoculated seals passed T. gondii oocysts in feces. This study
      demonstrates that T. gondii oocysts can establish viable infection in seals and
      supports the hypothesis that toxoplasmosis in marine mammals can be acquired from
      oocysts in surface water runoff and sewer discharge.

PMID- 15165048
TI  - Helminth infracommunities of Gallotia caesaris caesaris and Gallotia caesaris
      gomerae (Sauria: Lacertidae) from the Canary Islands (Eastern Atlantic).
AB  - A survey of gastrointestinal helminth communities of Gallotia caesaris caesaris
      (Lehrs, 1914) and G. c. gomerae (Boettger and MUller, 1914), from the islands of
      El Hierro and La Gomera, respectively, in the Canary Archipelago, Spain, was
      conducted to determine the prevalence, intensity, and diversity of intestinal
      parasites of these lacertid lizards. Larval forms of cestodes, nematodes, and
      acanthocephalans were found in the body cavity of G. c. caesaris; this lizard is
      the intermediate or paratenic host in the life cycle of these helminths.
      Pharyngodonid nematodes were the most common intestinal helminths in both hosts,
      4 of them being Gallotia spp. specialists. Helminth infracommunities of both
      hosts were depauperate and isolationist, according to the low values of helminth
      diversity.

PMID- 15165049
TI  - Description and proposed life cycle of Maritrema novaezealandensis n. sp.
      (Microphallidae) parasitic in red-billed gulls, Larus novaehollandiae scopulinus,
      from Otago Harbor, South Island, New Zealand.
AB  - Maritrema novaezealandensis n. sp. is described from Otago Harbor, South Island,
      New Zealand, on the basis of adult specimens collected from the Red-billed gull,
      Larus novaehollandiae scopulinus, and excysted metacercariae obtained from crabs.
      It belongs to the "eroliae group" and differs from other related species mainly
      in the shape, size, and patterns of distributions of the spines on the cirrus,
      the shape of the metraterm, the presence of an unlobed ovary, and the complete
      ring of the vitelline follicles. Based on morphometric features of metacercariae
      and adult specimens, the trophic relationships among invertebrate and vertebrate
      hosts, experimental infections, and previous reports of species of Maritrema with
      similar transmission patterns, the life cycle of M. novaezealandensis n. sp. is
      described. A 3-host life cycle is proposed for this parasite. The first
      intermediate host is the mud snail, Zeacumantus subcarinatus, in which the
      cercarial stage is produced in sporocysts located within the gonad of the snail.
      At least 3 crab species (Hemigrapsus crenulatus, Macrophtalmus hirtipes, and
      Halicarcinus whitei) and several species of amphipods act as second intermediate
      hosts, with metacercariae encysted in the body cavity of the crustacean host.
      Finally, the definitive host, the gull, L. n. scopulinus, harbors the adult worms
      in its intestine.

PMID- 15165050
TI  - Cloning, expression, and characterization of iron-containing superoxide dismutase
      from Neospora caninum.
AB  - A gene encoding superoxide dismutase (SOD) from Neospora caninum, a causative
      agent of neosporosis, has been cloned and its gene product functionally expressed
      and characterized. The gene had an open reading frame of 606 bp and deduced 201
      amino acids. Sequence analysis showed that the gene had conserved metal-binding
      residues and conserved amino acid residues that were found in Fe-SODs. Comparison
      of the deduced amino acid sequence of the enzyme with previously reported Fe-SOD
      amino acid sequences of the other parasitic protozoans revealed significant high
      homology. The coding region of the N. caninum Fe-SOD was cloned and functionally
      expressed in Escherichia coli. Enzyme activity of the expressed protein was
      inhibited by hydrogen peroxide but not by sodium azide and potassium cyanide, and
      the enzyme showed similar biochemical properties with typical Fe-SODs of other
      parasitic protozoans. Southern blot analysis showed that the SOD gene appears to
      be present as a single-copy gene in N. caninum genome. Semiquantitative reverse
      transcription-polymerase chain reaction and immunoblot using antiserum raised
      against the purified recombinant protein showed that Fe-SOD is expressed in both
      developmental stages of N. caninum, i.e., in bradyzoites and tachyzoites. In an
      immunofluorescence assay, the enzyme was localized on the cell surface of N.
      caninum tachyzoites. These results suggest that Fe-SOD might be essential for the
      intracellular survival of N. caninum and may play an important role in the
      pathogenesis of the parasite by protecting the parasite from oxidative killing.

PMID- 15165051
TI  - Five new species of Pedibothrium (Tetraphyllidea: Onchobothriidae) from the tawny
      nurse shark, Nebrius ferrugineus, in the Pacific Ocean.
AB  - The spiral intestines of 7 Tawny nurse sharks (Nebrius ferrugineus;
      Rhincodontidae) from Australia and French Polynesia were examined for tapeworms.
      These sharks hosted 5 new species of Pedibothrium. The 5 species were prepared
      for light and scanning electron microscopy. Whereas 3 of the species exhibit the
      bipronged hooks typical of members of Pedibothrium, 1 species was found to
      possess tiny unipronged hooks or to lack some, or all, hooks, and all individuals
      of the fifth species appeared to lack bothridial hooks entirely. Nonetheless, the
      otherwise remarkable similarities between these species and the species of
      Pedibothrium bearing bipronged hooks were considered to be sufficient to justify
      the placement of these 2 species in this genus. All 5 species possess proglottid
      features typical of Pedibothrium, including a uterus that extends anteriorly only
      to the level of the cirrus sac and a cirrus sac that is bent anteriorly and is
      crossed by the vagina. All 5 species also exhibit uniloculated bothridia. Of
      particular note was the fact that all 5 species exhibit bladelike spinitrichs
      with elongated distal tips, a form of microthrix currently known only from
      species of Pedibothrium. As a consequence, these species were treated as
      possessing modified hooks or as having lost hooks. The diagnoses of Pedibothrium
      and Onchobothriidae were emended to include these species. Each of the 5 new
      species bears a strong resemblance to 1 or more species of Pedibothrium hosted by
      a species of rhincodontid shark other than N. ferrugineus. Much of Southwell's
      type and voucher material of Pedibothrium was located and used to verify the
      identity of Pedibothrium kerkhami and many of the hosts from which Southwell's
      material of Pedibothrium was collected. This material suggests that P. kerkhami
      parasitizes Stegostoma fasciatum and not N. ferrugineus.

PMID- 15165052
TI  - Naiadocystis phykoterion n. gen., n. sp. (Apicomplexa: Eugregarinida:
      Hirmocystidae), from the Mexican pygmy grasshopper, Paratettix mexicanus
      (Orthoptera: Tetrigidae), in the Texas big thicket with recognition of three
      previously described species of Naiadocystis.
AB  - Naiadocystis phykoterion n. gen., n. sp. (Apicomplexa: Eugregarinida:
      Hirmocystidae), is described from the Mexican pygmy grasshopper, Paratettix
      mexicanus (Orthoptera: Tetrigidae), collected from sandbars along Harmon Creek,
      Walker County, Texas, in the western edge of the Texas Big Thicket. Naiadocystis
      n. gen. is distinguished by the form of the epimerite complex, a simple cordoid
      or toroid epimerite with an interior obconoid structure resembling a funnel that
      tapers to a distinct axial canal bisecting the protomerite, which is conspicuous
      in all stages of development, and a satellite protomerite reduced to a linearly
      crateriform cup or sucker that receives and enfolds posterior end of primite
      deutomerite. Association is precocious, caudofrontal, and biassociative.
      Gametocysts are spherical. Sporoducts are present but vestigial and irregular in
      number. Oocysts are broadly elliptoid with 4 small spherical polar knobs, 1 each
      at 30 degrees, 150 degrees, 210 degrees, and 330 degrees, and dehisce en masse.
      The species described herein are differentiated by their overall size and
      relative proportion of cellular structures. Naiadocystis acantholobae (Hoshide,
      1952) n. comb., Naiadocystis acrydiinarum (Semans, 1939) n. comb., and
      Naiadocystis tetrigis (Corbel, 1968) n. comb. are recognized as members of
      Naiadocystis previously placed within Gregarina (Apicomplexa: Eugregarinida:
      Gregarinidae).

PMID- 15165053
TI  - Himasthla escamosa n. sp. (Digenea: Echinostomatidae) from the kelp gull, Larus
      dominicanus (Charadriiformes: Laridae), on the Patagonian coast, Argentina.
AB  - In this article, we describe a new species of Himasthla Dietz, 1909 (Digenea:
      Echinostomatidae) from Larus dominicanus Lichtenstein (Aves: Laridae) in northern
      Patagonia, Argentina. We also describe the hosts, localities, and key diagnostic
      features and the measurements of the so far 25 described species. Of these
      species. Himasthla militaris, H. leptosoma, H. elongata, H. secunda, H.
      megacotyla, H. multilecithosa, H. piscicola, H. compacta, H. schachtachtinskoi,
      H. littorinae, H. continua, H. avosettae, and H. interrupta are similar to H.
      escamosa n. sp. in having 29 head collar spines. Himasthla leptosoma, H.
      piscicola, H. multilecithosa, H. interrupta, H. continua, and H. militaris can be
      differentiated from the new species mainly by the extension of the vitellaria.
      Himasthla avosettae, H. megacotyla, H. elongata, H. compacta, and H. littorinae
      have a different size or arrangement (or both) of head collar spines compared
      with H. escamosa. Himasthla secunda can be distinguished from H. escamosa n. sp.
      in having a larger body, testes, and ovary and a different position of the ovary.
      The comparison with H. schachtachtinskoi could not be done because the
      bibliography was not available. This is the first record of the genus in
      Argentina and from L. dominicanus.

PMID- 15165054
TI  - Bathycestus brayi n. gen. and n. sp. (Cestoda: Pseudophyllidea) from the deep-sea
      fish Notacanthus bonaparte in the northeastern Atlantic.
AB  - Bathycestus brayi n. gen., n. sp. (Pseudophyllidea: Triaenophoridae) is proposed
      to accommodate a new cestode from a deep-sea fish, the shortfin spine eel
      Notacanthus bonaparte (Notacanthiformes: Notacanthidae), from the northeastern
      Atlantic. The new genus is placed in the Triaenophoridae because it possesses a
      uterine pore on the ventral surface, a marginal genital pore, and a follicular
      vitellaria. Bathycestus most closely resembles Eubothrioides, Fistulicola,
      Probothriocephalus, and Pseudeubothrioides, which have also an unarmed scolex, a
      single set of genital organs per proglottid, an unarmed cirrus, cortical
      vitellaria, and a compact rather dendritic ovary. It differs from these genera by
      combination of the following features: a sagittate scolex with a weakly developed
      apical disc and free posterior margins of bothria, no neck, a long cirrus sac,
      reaching to the median third of proglottids and angled anteromedially in its
      proximal part, the posterior position of the vagina in relation to the cirrus
      sac, the testes in 2 lateral fields confluent postovarially, circumcortical
      vitellaria continuous longitudinally, and unoperculate eggs. Bathycestus brayi n.
      sp. is the first cestode to be described from a deep-sea fish of the genus
      Notacanthus.

PMID- 15165055
TI  - Micropleura australiensis n. sp. (Nematoda: Micropleuridae) from the body cavity
      of Crocodylus johnsoni in Western Australia.
AB  - A new nematode species, Micropleura australiensis n. sp., is described on the
      basis of specimens found in the peritoneal cavity of the Australian freshwater
      crocodile, Crocodylus johnsoni Krefft, from the Ord River area, Western
      Australia. The new species is mainly characterized by the length of spicules
      (0.360-0.366 mm) and gubernaculum (0.096-0.105 mm), the number and arrangement of
      male caudal papillae (4 preanal and 6 postanal pairs), and the postequatorial
      vulva. To date, it is the first species of Micropleura reported from Australia.
      Micropleura trionyxi Agrawal, 1966, and M. lissemysia Chattervati, 1985, are
      considered junior synonyms of M. indica Khera, 1951.

PMID- 15165057
TI  - Herpetomonas ztiplika n. sp. (Kinetoplastida: Trypanosomatidae): a parasite of
      the blood-sucking biting midge Culicoides kibunensis Tokunaga, 1937 (Diptera:
      Ceratopogonidae).
AB  - Herein, we describe the first case of a natural infection of biting midges by a
      kinetoplastid protozoan. Flagellates from a female Culicoides kibunensis captured
      in a bird's nest were introduced into culture and characterized by light and
      electron microscopy. However, because the morphological data were inconclusive,
      the novel endosymbiont-free trypanosomatid was assigned into Herpetomonas
      primarily on the basis of the 18S and 5S ribosomal RNA (rRNA) gene sequences.

PMID- 15165056
TI  - Dactylogyrids (Platyhelminthes: Monogenoidea) parasitizing butterfly fishes
      (Teleostei: Chaetodontidae) from the coral reefs of Palau, Moorea, Wallis, New
      Caledonia, and Australia: species of Euryhaliotrematoides n. gen. and Aliatrema
      n. gen.
AB  - Seven species of Euryhaliotrematoides n. gen. and 1 species of Aliatrema n. gen.
      (Monogenoidea; Dactylogyridae) are described and reported from the gills of 15
      species of butterfly fishes (Chaetodontidae) from the coral reefs of Moorea
      (French Polynesia), Wallis (Wallis and Futuna), Heron and Lizard (Australia),
      Palau (Micronesia), and New Caledonia: Aliatrema cribbi n. sp. from Chaetodon
      auriga, Chaetodon lunula, Chaetodon trifasciatus, Chaetodon ulietensis, Chaetodon
      vagabundus, Forcipiger flavisissimus, and Heniochus chrysostomus;
      Euryhaliotrematoides annulocirrus n. comb. from C. auriga, C. lunula, and C.
      vagabundus; Euryhaliotrematoides aspistis n. sp. from C. auriga, Chaetodon
      citrinellus, C. lunula, Chaetodon reticulatus, C. ulietensis, and C. vagabundus;
      Euryhaliotrematoides berenguelae n. sp. from C. citrinellus, Chaetodon
      ornatissimus, and F. flavisissimus; Euryhaliotrematoides grandis n. comb. from C.
      auriga, C. citrinellus, Chaetodon ephippium, Chaetodon kleinii, Chaetodon
      lineolatus, C. lunula, C. ornatissimus, C. trifasciatus, C. vagabundus, and H.
      chrysostomus; Euryhaliotrematoides microphallus n. comb. from C. auriga, C.
      citrinellus, C. ephippium, C. kleinii, C. lunula, C. ornatissimus, C.
      reticulatus, Chaetodon trifascialis, C. trifasciatus, C. vagabundus, F.
      flavisissimus, and H. chrysostomus; Euryhaliotrematoides pirulum n. sp. from C.
      auriga, C. citrinellus, C. lunula, C. trifasciatus, and C. vagabundus; and
      Euryhaliotrematoides triangulovagina n. comb. from C. auriga, C. citrinellus, C.
      kleinii, C. lunula, C. ornatissimus, C. vagabundus, F. flavisissimus, H.
      chrysostomus, and Hemitaurichthys polylepis. All reports of previously described
      species are new locality records. With exceptions of E. grandis and E.
      annulocirrus on C. auriga and C. lunula and E. triangulovagina and E.
      microphallus on C. auriga, all reports are new host records. Haliotrema
      hainanensis and H. affinis are considered junior subjective synonyms of E.
      triangulovagina and E. annulocirrus, respectively. Aliatrema n. gen. is
      characterized by marine dactylogyrids with tandem gonads (germarium
      pretesticular), haptoral hooks with upright acute thumbs, a coiled copulatory
      organ with counterclockwise rings and funnel-shaped base but lacking an accessory
      piece, and a dextral vaginal pore. Euryhaliotrematoides n. gen. is characterized
      by marine dactylogyrids having tandem gonads (germarium pretesticular), haptoral
      hooks with upright acute thumbs, a coiled copulatory organ with counterclockwise
      rings and funnel-shaped base, a vas deferens looping the left intestinal cecum,
      and a dextral vaginal pore.

PMID- 15165058
TI  - Species of Eimeria (Apicomplexa: Eimeriidae) from bats (Chiroptera:
      Vespertilionidae) in central Wyoming.
AB  - Feces from 60 bats representing 5 species and 4 genera collected in central
      Wyoming in 2001 were examined for the presence of coccidia. Two species of
      Eimeria were identified in 4 bats representing 2 species of Myotis. All infected
      animals harbored a single species; there was no multispecies infection. Eimeria
      catronensis was recovered from 3 little brown bats (Myotis lucifugus), and
      Eimeria californicensis was identified from a single long-legged myotis (Myotis
      volans). Both represent new geographic records and the second a new host record.
      Eimeria catronensis-like oocysts were recovered from a single silver-haired bat
      (Lasionycteris noctivagans). Descriptions and taxonomic summaries for the
      eimerian species are presented in this study.

PMID- 15165059
TI  - Hepatozoon sauritus: a polytopic hemogregarine of three genera and four species
      of snakes in north Florida, with specific identity verified from genome analysis.
AB  - Hemogregarines from Thamnophis s. sirtalis, Coluber constrictor priapus, Elaphe
      obsoleta quadrivittata, and E. g. guttara in northern Florida appeared to be
      conspecific on the basis of similar gamonts from all the hosts and sporogonic
      stages obtained from 3 hosts. The resemblance of gamonts to those of Hepatozoon
      sauritus, described from T. sauritus sackenii in southern Florida, justified
      comparison of DNA isolates from the type infection of H. sauritus with samples
      from each of the northern Florida hosts and with a morphologically distinct
      species, H. sirtalis, from northern Florida. A nucleotide sequence (530 bp)
      alignment of the 18S ribosomal RNA gene revealed 2 hemogregarine haplotypes that
      varied at 15 sites (p distance = 2.8%), which included 10 transitions and 5
      transversions. Two well-supported clusters (100% bootstrap support) were revealed
      by a neighbor-joining tree topology. One cluster included the type infection of
      H. sauritus and all 4 of the other samples from the northern Florida hosts, with
      samples of H. sirtalis comprising a second cluster. Hepatozoon sauritus,
      therefore, is a polytopic species in contrast to the 8 other Hepatozoon species
      thus far described from snakes in Florida, each of which appears to parasitize a
      single host species.

PMID- 15165060
TI  - Parallopharynxs pp. (Trematoda: Digenea: Plagiorchioidea) in iguanian lizards
      from the Area de Conservacion Guanacaste, Guanacaste, Costa Rica, including
      Parallopharynx matternae n. sp. in Chaetodon basiliscus (Squamata: Iguania:
      Corytophanidae).
AB  - We report 3 species of the digenean genus Parallopharynx, 1 previously
      undescribed, from the Area de Conservacion Guanacaste (ACG) in northwestern Costa
      Rica. Parallopharynx gonzalezi, which was originally described in Basiliscus sp.
      and Ctenosoura similis from central Costa Rica, inhabits C. quinquecarinata; P.
      jonesi, originally described in Anolis lionotus (syn. Norops oxylophus) from
      Nicaragua, inhabits N. oxylophus, N. biporcatus, and Basiliscus basiliscus; and
      the new species, which inhabits B. basiliscus. Parallopharynx matternae n. sp.
      differs from all other members of the genus by having a metraterm extending
      posteriad from the genital pore to the posterior margin of the ventral sucker,
      whereas in P. arctus and P. gonzalezi, the metraterm never surpasses the midlevel
      of the ventral sucker and in P. jonesi it never passes the anterior margin of the
      ventral sucker, and by having an oral sucker that does not exceed 150 microm in
      diameter with a subsequent greater oral-ventral sucker width ratio ranging from
      1:0.88-1.12 (averaging 1:1), whereas values range from 1:0.71-0.83 for P.
      gonzalezi and P. arctus, and from 1:0.59-0.68 for P. jonesi. Parallopharynx spp.
      possesses Y-shaped excretory vesicles with a long central stem and short arms
      bifurcating immediately posterior to the ovary; similar to those found in members
      of the Telorchiidae. Additional similarities in the relative positions of the
      gonads and the structure of the cirrus sac and metraterm indicate a close
      relationship between Parallopharynx and members of the Telorchiidae.

PMID- 15165061
TI  - Procyrnea chabaud, 1958 (Nematoda: Habronematoidea: Habronematidae) in birds from
      the Area de Conservacion Guanacaste, Costa Rica, including descriptions of 3 new
      species.
AB  - Four species of Procyrnea were collected in birds from the Area de Conservacion
      Guanacaste, Costa Rica. Procyrnea brevicaudata n. sp. in Crypturellus cinnamomeus
      resembles P. ficheuri, P. murrayi, P. ameerae, P. dollfusi, and P. aptera in
      lacking lateral alae but differs from all these species in having 2 longitudinal
      ridges on the left side of the body, in having a sinistral rather than ventral
      vulvar opening, and in having dorsally bent rather than straight female tails.
      Procyrnea mawsonae n. sp., in Buteo magnirostris, is similar to P. strialata in
      body size and in having 2 transverse striated lateral alae, but differs by having
      longer and differently shaped spicules, and by lacking a single preanal sessile
      papilla. Procyrnea mclennanae n. sp., in Heliomaster constantii, is similar to P.
      strialata (Zhang, 1991) and P. mawsonae n. sp. in having 2 transverse striated
      lateral alae, but it can be distinguished from P. strialata and P. mawsonae in
      having 4 rather than 3 small teeth on the interior border of the pseudolabia, in
      having unequal rather than equal lateral alae, and in having longer spicules.
      Procyrnea sp., on the basis of a single adult male in Campephilus guatemalensis,
      resembles P. suraiyae, P. tulostoma, and P. unilateralis in possessing a single
      and long lateral ala, but can be distinguished from P. suraiyae and P. tulostoma
      in the length of the left spicule, in the left spicule having a bifid distal end,
      the right spicule having a rounded distal end rather than both spicules having
      pointed distal ends, and in having the lateral ala beginning at the lip region
      instead of posterior to the cervical papillae. It differs from P. uncinipenis in
      having a spicule ratio of 1:3.5 rather than 1:2.5, in the left spicule having a
      bifid rather than alate distal end, and in the absence of a single preanal
      papilla.

PMID- 15165062
TI  - Recognition of Entamoeba histolytica 115-kDa surface protein by human secretory
      immunoglobulin A antibodies from asymptomatic carriers.
AB  - Entamoeba histolytica is a protozoan parasite that can invade the intestinal
      mucosa. Infection induces production of secretory immunoglobulin A (SIgA)
      antibodies that can diminish the adhesion between E. histolytica trophozoites and
      epithelial cells in vitro and reduce the rate of new infections in children. SIgA
      antibodies produced by asymptomatic cyst carriers could play a protective role
      against the damage caused by E. histolytica. To identify membrane antigens
      capable of inducing SIgA response in E. histolytica cyst carriers, salivary SIgA
      antibodies were confronted with blotted plasma membrane proteins from amebae. A
      surface 115-kDa ameba protein was recognized by 62% of the human SIgA antibodies
      tested. The 115-kDa protein is not a mannose-containing glycoprotein and has no
      protease activity. Rabbit anti-115-kDa protein antibodies were capable of
      reducing erythrophagocytosis but were unable to protect culture cells from the
      cytopathic damage caused by E. histolytica. However, anti-115-kDa protein
      antibodies induced surface receptor redistribution.

PMID- 15165063
TI  - Evaluation and comparison of an indirect fluorescent antibody test for detection
      of antibodies to Sarcocystis neurona, using serum and cerebrospinal fluid of
      naturally and experimentally infected, and vaccinated horses.
AB  - The objectives of this study were to evaluate the accuracy of the indirect
      fluorescent antibody test (IFAT) using serum and cerebrospinal fluid (CSF) of
      horses naturally and experimentally infected with Sarcocystis neurona, to assess
      the correlation between serum and CSF titers, and to determine the effect of S.
      neurona vaccination on the diagnosis of infection. Using receiver-operating
      characteristic analysis, the areas under the curve for the IFAT were 0.97 (serum)
      and 0.99 (CSF). Sensitivity and specificity were 83.3 and 96.9% (serum, cutoff
      80) and 100 and 99% (CSF, cutoff 5), respectively. Titer-specific likelihood
      ratios (LRs) ranged from 0.03 to 187.8 for titers between <10 and 640. Median
      time to conversion was 22-26 days postinfection (DPI) (serum) and 30 DPI (CSF).
      The correlation between serum and CSF titers was moderately strong (r = 0.6) at
      30 DPI. Percentage of vaccinated antibody-positive horses ranged from 0 to 95%
      between 0 and 112 days after the second vaccination. Thus, the IFAT was reliable
      and accurate using serum and CSF. Use of LRs potentially improves clinical
      decision making. Correlation between serum and CSF titers affects the joint
      accuracy of the IFAT; therefore, the ratio of serum to CSF titers has potential
      diagnostic value. The S. neurona vaccine could possibly interfere with equine
      protozoal myeloencephalitis diagnosis.

PMID- 15165064
TI  - Serodiagnosis of canine Babesia gibsoni infection by enzyme-linked immunosorbent
      assay with recombinant P50 expressed in Escherichia coli.
AB  - The entire P50 gene encoding a surface protein of Babesia gibsoni was cloned into
      the bacteria expression vector pGEX-4T-3 and subsequently expressed in
      Escherichia coli as a glutathione S-transferase fusion protein. The purified
      recombinant P50 was evaluated in an enzyme-linked immunosorbent assay (ELISA) for
      the serological diagnosis of B. gibsoni infection in dogs. ELISA was able to
      differentiate clearly among B. gibsoni-infected, Babesia canis-infected, and
      uninfected dog sera. The antibody response against the recombinant P50 was
      maintained at a high level until the chronic stage of infection in dogs
      experimentally infected with B. gibsoni. When serum samples collected from
      domestic dogs in Japan were examined for the diagnosis of B. gibsoni infection by
      the ELISA, 3 of 209 samples (1.4%) were positive for the antibody to B. gibsoni.
      This result was completely identical to those of Western blot analysis and the
      indirect fluorescent antibody test. These results indicate that the recombinant
      P50 expressed in E. coil is a useful diagnostic antigen for practical use in the
      diagnosis of B. gibsoni infection in dogs.

PMID- 15165065
TI  - Prenatal Schistosoma japonicum infection in piglets: effect of repeated exposure
      of the dams on treatment efficacy and susceptibility to challenge infections.
AB  - This study elucidated the fate of prenatal infections in piglets born by dams
      repeatedly infected before and during pregnancy with Schistosoma japonicum.
      Independent variables included repeated infections of the dams and treatment or
      challenge infection (or both) of the prenatally exposed piglets. Dependant
      variables were worm counts, fecal and tissue egg counts, weight gain, and gross
      pathological observations. Fifteen female piglets (the dams) were included, of
      which 6 received repeated infections with S. japonicum during 6 mo. All dams were
      inseminated and 10 wk pregnant; 12 of the dams were infected with S. japonicum,
      of which 6 had been repeatedly infected. Three dams remained uninfected. Eight
      weeks after delivery, the prenatally exposed piglets (the offspring) were
      grouped, and 6 of the 12 groups were treated with praziquantel. Four weeks after
      treatment, 5 groups of piglets were infected with S. japonicum. Groups of piglets
      were killed either 12 or 22 wk after delivery. Repeated infections of the dam did
      not prevent establishment of a congenital infection in the pig fetuses. Piglets
      born with a congenital infection were not resistant to a S. japonicum challenge
      infection given 12 wk after birth. Neither did praziquantel effectively cure the
      piglets nor did treatment of the prenatally infected piglets prevent
      establishment of a challenge infection given 4 wk after treatment. Results of the
      present study indicate that prenatal exposure, independently of the dam's
      infection status, may change the host response to challenge infections and
      treatment after birth.

PMID- 15165066
TI  - Detection of cryptosporidium antibodies in sera and oral fluids using multiplex
      bead assay.
AB  - For the first time, a multiplex bead assay (MBA) was used to assay oral fluid and
      serum specimens for immunoglobulin G (IgG) antibodies to specific Cryptosporidium
      parvum antigens that were coupled to polystyrene beads. Recombinant C. parvum 17-
      and 27-kDa antigens (r17 and r27, respectively) both linked with glutathione-S
      transferase (GST) fusion proteins, native 17-kDa antigen, and GST alone were each
      coupled to microspheres that could be differentiated based on variable amounts of
      internally incorporated red fluorescent dye. Initial and follow-up serum and oral
      fluid specimens from a 1997 cryptosporidiosis outbreak in Spokane, Washington,
      were incubated with the coupled beads. Antibodies bound to the coupled beads were
      detected using biotinylated monoclonal anti-human IgG antibody and streptavidin
      labeled r-phycoerythrin. Fluorescence intensity was measured by flow cytometry.
      For the 3 C. parvum antigens, the median of the mean fluorescence intensity (MFI)
      was significantly higher (P < 0.03) in the initial specimens than in the follow
      up specimens. No significant change in IgG responses to GST in oral fluids or
      serum specimens was observed. For all Cryptosporidium antigens, the MFI in the
      initial serum specimens correlated with the MFI in the initial oral fluid
      specimens (P < 0.001, r > 0.673). For the recombinant antigens used in the MBA,
      the MFI correlated with the response as measured by an enzyme-linked
      immunosorbent assay that used r17 and r27 expressed without the GST fusion
      partner (P < 0.001, r > 0.854). MBA using sera or more conveniently collected
      oral fluids, especially from children, may be an option for immunodiagnosis of C.
      parvum infection and for prospective epidemiological studies designed to monitor
      infection risk.

PMID- 15165067
TI  - Infection by anisakid nematodes contracaecum spp. in the Mayan cichlid fish
      'Cichlasoma (Nandopsis)' urophthalmus (Gunther 1862).
AB  - Larval nematodes that parasitize the Mayan cichlid fish 'Cichlasoma (Nandopsis)'
      urophthalmus (Gunther 1862) in southern Florida were identified as Contracaecum
      spp. (Nematoda: Anisakidae, Anisakinae). The objective of this study was to
      determine whether infection intensity and prevalence of these parasites differ
      between a brackish water and freshwater habitat or through ontogeny in the
      freshwater habitat only. The nematodes were removed from the abdominal cavity of
      the fishes and counted. Infection intensity was compared between habitats using
      analysis of covariance and evaluated through ontogeny using Spearman rank order
      correlation. Prevalence was compared between habitats and between adults and
      juveniles from the freshwater habitat using a z-test. Although infection
      intensity did not differ between habitats, infection prevalence was greater at
      the freshwater site (FWS). Both the prevalence and intensity of nematode
      infection increased through ontogeny at the FWS, and no nematode was found in
      fishes that were smaller than 93 mm standard length. Thus, the parasites appear
      to accumulate during the lifetime of the fishes.

PMID- 15165069
TI  - Toxoplasmosis in an elephant seal (Mirounga angustirostris).
AB  - Toxoplasma gondii infections in fish-eating marine mammals is intriguing and
      indicative of contamination of the sea environment with oocysts. Toxoplasma
      gondii was identified in an elephant seal (Mirounga angustirostris) that had
      encephalitis. Tissue cysts were found in sections of cerebrum, and the diagnosis
      was confirmed by immunohistochemical staining with T. gondii-specific polyclonal
      rabbit serum. This is the first report of T. gondii infection in an elephant
      seal.

PMID- 15165068
TI  - Ex vivo anthelmintic activity of albendazole-sulphoxide enantiomers.
AB  - The antiparasitic activity of racemic albendazole-sulphoxide (Ricobendazole =
      racRBZ) and its (+) and (-) enantiomers was tested in an ex vivo murine model for
      Trichinella spiralis infection. Larvae were isolated from the muscle of infected
      mice and exposed to concentrations between 0.01 and 1 microg/ml of the racemic
      mixture or to each of its enantiomers. The activity of each compound was then
      assayed by measuring the ability of the treated larvae to infect naive mice
      (larval viability). At a concentration of 0.5 microg/ml, all 3 compounds were
      highly effective in reducing the viability of the larvae, achieving reductions of
      91.26% (racRBZ), 96.7% (+), and 89.2% (-), when compared with untreated controls.
      At lower concentrations (0.1 microg/ml), only treatment with (+)RBZ rendered a
      significant reduction in larval viability in comparison with controls (84.3%; P <
      0.01), whereas at 0.01 microg/ml, none of the compounds altered larval viability
      (P > 0.05).

PMID- 15165070
TI  - Isolation and genotyping of Toxoplasma gondii from free-ranging chickens from
      Mexico.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the presence of T. gondii oocysts in the environment because chickens feed
      from the soil. In the present study, prevalence of T. gondii in 208 free-range
      chickens (Gallus domesticus) from Mexico was investigated. Blood, heart, and
      brain from each animal were obtained to test for T. gondii infection. Antibodies
      to T. gondii, assayed with the modified agglutination test (1:10 or higher), were
      found in 13 (6.2%) chickens. Hearts and brains of 13 seropositive chickens were
      bioassayed in mice, and T. gondii was isolated from 6 chickens. All 6 isolates
      were avirulent for mice. Genotyping of chicken isolates of T. gondii using the
      SAG2 locus indicated that 5 were type III and 1 was type I. This is the first
      report of isolation of T. gondii from chickens from Mexico.

PMID- 15165071
TI  - Clinostomum complanatum and Clinostomum marginatum (Rudolphi, 1819) (Digenea:
      Clinostomidae) are separate species based on differences in ribosomal DNA.
AB  - Infections by metacercariae of Clinostomum (Leidy, 1856) species adversely affect
      aquacultured fish and are potentially transmissible to humans. Molecular
      methodologies are efficient tools, which enable diagnosis of all life-history
      stages of trematodes in their diverse hosts. The small subunit of ribosomal DNA
      genes of adults of the Old World Clinostomum complanatum (Rudolphi, 1819) and the
      New World Clinostomum marginatum (Rudolphi, 1819), obtained from a little egret
      Egretta garzetta (Linnaeus, 1766) and the great blue heron Ardea herodias
      (Linnaeus, 1758), respectively, were amplified, sequenced, and aligned. The
      resulting alignment was used to develop a genetic assay to differentiate between
      these species.

PMID- 15165072
TI  - Patterns of occurrence of the platyhelminth parasites of the wild bullseye puffer
      (Sphoeroides annulatus) off Sinaloa, Mexico.
AB  - This study provides basic information on the occurrence of platyhelminths in the
      wild bullseye puffer (Sphoeroides annulatus) from Sinaloa, Mexico. Specimens of
      pufferfish were collected from 2 localities: Teacapan (n = 161) and Mazatlan (n =
      66). Six species of platyhelminths were recorded: 2 monogeneans (Diclidophoridae:
      Heterobothrium ecuadori and Capsalidae: Neobenedenia melleni) and 4 digeneans
      (Apocreadiidae: Homalometron longisinosum, Lepocreadiidae: Bianium plicitum,
      Gorgoridae: Phyllodristomum mirandai, and Fellodistomidae: Lintonium vibex). This
      is the first record of the platyhelminth L. vibex in S. annulatus in the Mexican
      Pacific. Bianium plicitum was the most abundant species, and H. ecuadori was the
      most prevalent species. The fish from Teacapan had the higher prevalence of
      platyhelminths. Teacapan had higher specific richness index, whereas Mazatlan had
      a higher dominance, 3.098 (Teacapan = 2.38). A relative risk analysis showed that
      B. plicitum was more likely to be present on fish in water within the temperature
      range of 21-25 C and from Teacapan compared with fish from the warmer water (26
      30 C) or from Mazatlan. Heterobothrium ecuadori was more likely to be present at
      water temperatures of 23-24.5 C on fish from Teacapan and when other
      ectoparasites were present. Neobenedenia melleni also was more likely to be
      present when other parasites were present.

PMID- 15165073
TI  - Gastrointestinal helminths of Cuvier's beaked whales, Ziphius cavirostris, from
      the western Mediterranean.
AB  - We examined the gastrointestinal helminth fauna of 2 Cuvier's beaked whales,
      Ziphius cavirostris, stranded on the Spanish Mediterranean coast. Information
      regarding intestinal parasites of this species is provided for the first time.
      Six helminth taxa were identified. Thirty type II larvae of the nematode Anisakis
      sp. were found in the stomach and the intestine of both hosts; 2 type I larvae of
      Anisakis sp. were found in the intestine of 1 host. One juvenile of the
      acanthocephalan Bolbosoma vasculosum was found in the intestine; the metacestode
      Scolex pleuronectis was found mainly in the terminal colon and the anal crypts of
      both hosts; adult cestodes of Tetrabothrius sp., which may represent a new
      species, were collected from the duodenum of 1 host. Composition of the
      intestinal parasitic community is similar to that of other oceanic cetaceans,
      which mostly include species of Bolbosoma and tetrabothriids (Cestoda).

PMID- 15165074
TI  - Determination of poultry feed-through insecticide activity in an in vivo
      anticoccidial assay.
AB  - The ability of an in vivo anticoccidial assay to identify potential feed-through
      insecticides was demonstrated using first-instar Lucilia sericata on droppings
      from chicks fed medicated diets. Cyromazine, a commercially available feed
      through insect growth regulator, ivermectin, diflubenzuron, fipronil, permethrin,
      and 2 experimental compounds were effective in varying degrees in killing L.
      sericata larvae. Eleven coccidiostats were effective against the protozoan
      parasites (Eimeria spp.) at commercially used levels, whereas they were
      ineffective against Lucilia larvae.

PMID- 15165075
TI  - Effects of snail size and diet on encystment of Echinostoma caproni cercariae in
      juvenile Helisoma trivolvis (Colorado strain) and observations on survival of
      infected snails.
AB  - The effects of snail size and diet on encystment of Echinostoma caproni cercariae
      in juvenile Helisoma trivolvis (Colorado strain) snails were studied. Encystment
      in neonatal (<1-mm shell diameter) and juvenile (2- to 3-mm shell diameter)
      snails was compared 24 hr postinfection (PI) after individual exposure of snails
      of each size to 1, 5, 10, 25, or 50 cercariae. Significantly more cysts were
      recovered from juvenile snails exposed to 10, 25, or 50 cercariae than from
      neonatals with comparable exposure. The maximum number of cysts recovered from
      juveniles exposed to 50 cercariae was 42, compared with a maximum of 15 cysts in
      neonatals comparably exposed. Size of H. trivolvis was a major factor in
      determining cyst burden in this planorbid. A diet of either Romaine lettuce leaf
      or hen's egg yolk did not have a significant effect on the number of cysts
      recovered at 24 hr PI from juvenile snails exposed to 25 or 75 cercariae.
      Survival of infected versus uninfected neonatals was also examined for 7 days.
      Neonatals exposed to 10 cercariae showed a significant decrease in survival at 6
      and 7 days PI when compared with uninfected controls.

PMID- 15165076
TI  - Occurrence of Proteocephalus tetrastomus (Rudolphi, 1810) (Cestoda:
      Proteocephalidea) in larval rainbow smelt (Osmerus mordax) in North America:
      identification of a potential pathogen confirmed.
AB  - A morphological evaluation and genetic analysis (sequencing of ITS2 region of
      rDNA) of proteocephalidean cestodes from rainbow smelt (Osmerus mordax) in the
      Saint Lawrence Estuary, Canada, has shown their conspecificity with
      Proteocephalus tetrastomus, a specific parasite of smelt (Osmeridae), previously
      known only from northern Europe, Russia, and Japan. The parasite occurs only in
      larval, but not adult, smelt in the Saint Lawrence Estuary. Prevalence of larval
      smelt infection was 42% (n = 50), mean intensity 2.1 +/- 2.4 and mean abundance
      1.1 +/- 1.0.

PMID- 15165077
TI  - Cell-mediated immune responses in horses with equine protozoal myeloencephalitis.
AB  - Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses
      from the Americas and is mainly caused by Sarcocystis neurona. Cell-mediated
      immune responses to mitogens have been shown to be reduced in horses with EPM,
      although it is not known whether the parasite causes this immunosuppression or if
      the immunosuppression is required for disease manifestation. Recently, a 29-kDa
      surface antigen from S. neurona merozoites was identified as being highly
      immunodominant on Western blot. This antigen has been sequenced and cloned, and
      the expressed protein has been named SnSAG1. Isolated peripheral blood
      lymphocytes from 43 EPM-negative horses and 28 horses with clinical EPM were
      cocultured with a mitogen or SnSAG1, and lymphocyte blastogenic responses to
      these antigens was measured by tritiated thymidine uptake. The ability of SnSAG1
      to induce gamma-interferon (gammaIFN) production was also investigated with
      reverse transcriptase-polymerase chain reaction. There was no significant
      differences between EPM-positive and -negative horses in lymphocyte responses to
      ConcanavalinA. However, lymphocytes from EPM-negative horses responded
      significantly higher to SnSAG1 than lymphocytes from EPM-positive horses.
      GammaIFN production was detectable by 24 hr in culture in response to SnSAG1 in
      all EPM-negative horses. There was still no detectable gammaIFN production in EPM
      positive horses after 72 hr in culture. It appears that the parasite is also able
      to induce an immunosuppression toward parasite-derived antigens as parasite
      specific responses are decreased.

PMID- 15165078
TI  - Fasciola hepatica: the growth and larval productivity of redial generations in
      Galba truncatula subjected to miracidia differing in their mammalian origin.
AB  - Experimental infections of Galba truncatula with 4 isolates of Fasciola hepatica
      miracidia differing by their mammalian origin (cattle, nutrias, rabbits, or
      sheep) were carried out to determine if parasite origin had an effect on the
      number of free rediae, their growth, and their larval productivity in each redia
      category. The mammalian origin of miracidia had a significant influence on the
      numbers of free rediae (they were higher in cattle-group snails) and the lengths
      of rediae (they were lower in rabbit groups). The redia category had also a
      significant effect on body and pharyngeal measurements. In all groups, the
      majority of cercariae (55.8-63.2%) were produced by the daughter rediae (R2a
      rediae) originating from the first mother redia. Compared with the other groups,
      the mean number of cercariae at day 49 postexposure was twice as high in cattle
      groups. In contrast, the mean number of daughter rediae produced by each second
      appearing mother redia or each R2a redia was higher in the nutria, rabbit, and
      sheep groups. The mammalian origin of F. hepatica miracidia had an effect on the
      number of live rediae, their length, and their redial and cercarial productivity.

PMID- 15165079
TI  - Epizootiology of Plasmodium hermani in Florida: chronicity of experimental
      infections in domestic turkeys and northern bobwhites.
AB  - A pen-reared northern bobwhite and a domestic turkey were infected with a strain
      of Plasmodium hermani obtained originally from a wild turkey in southern Florida.
      Blood films from these 2 birds were positive microscopically for 188 and 370 days
      postinfection (PI), respectively. Culicine mosquitoes (Culex nigripalpus and C.
      salinarius) were blood fed on the bobwhite and the turkey at different times
      during the infection and used to transmit the malaria to other bobwhites and
      turkeys up to days 298 and 473 PI, respectively. It was concluded that in nature,
      P. hermani could remain in a chronic phase in avian hosts for a year, or longer,
      allowing survival of the parasite between seasons of mosquito transmission.

PMID- 15165080
TI  - Development of nestedness: host biology as a community process in parasite
      infracommunities of yellow perch (Perca flavescens (Mitchill)) from Garner Lake,
      Alberta.
AB  - Infracommunity data from 60 perch collected from Garner Lake, Alberta, in 1992
      were examined to determine whether ontogenetic shifts in host diet or habitat
      could produce a nested subset pattern of infracommunity structure. The host by
      parasite matrix showed significant nesting. Host idiosyncratic temperatures,
      which are indicative of differing "biogeographic histories," were determined
      primarily by the presence of Ergasilus caeruleus in depauperate communities, or
      its absence in richer communities, and covaried positively with host age and the
      associated variables of host length, mass, and infracommunity richness.
      Idiosyncratic host temperatures did not differ significantly between male and
      female perch when the effect of age was controlled for by analysis of covariance.
      Although an ontogenetic diet shift can be ruled out as producing the observed
      nested pattern, it is possible that the observed nested subset pattern is the
      result of an ontogenetic habitat shift.

PMID- 15165081
TI  - Serologic prevalence of Toxoplasma gondii in field mice, Microtus fortis, from
      Yuanjiang, Hunan Province, People's Republic of China.
AB  - Antibodies to Toxoplasma gondii were investigated in serum samples of field mice,
      Microtus fortis, from Yuanjiang, Hunan Province, People's Republic of China. The
      modified agglutination test (MAT) incorporating formalin-fixed whole tachyzoites
      and mercaptoethanol was used to determine antibodies. Antibodies to T. gondii
      (MAT > or = 1:20) were found in 36 (29%) of 124 trapped mice. The antibody titers
      of positive sera (percentage in parentheses) were 1:20 (8.9), 1:40 (3.2), 1:80
      (3.2), 1:160 (1.6), 1:320 (1.6), 1:640 (1.6), 1:1,280 (1.6), 1: 2,560 (0.8), and
      > 1:2,560 (6.5). No antibody to T. gondii was found in 104 sera of laboratory
      bred M. fortis infected with Schistosoma japonicum between 1 and 45 days after
      infection.

PMID- 15165082
TI  - Pain experienced by lung cancer patients: a review of prevalence, causes and
      pathophysiology.
AB  - BACKGROUND: Lung cancer is one of the commonest cancers to cause pain, but little
      is known regarding the extent of this complex problem in these patients. METHODS:
      Medline (1966-June 2002) and Cancerlit (1975-May 2002) were searched to identify
      studies of lung cancer patients' experience of pain, its prevalence, causes and
      underlying pathophysiology. RESULTS: Thirty-two studies were identified. Patients
      were recruited from diverse populations, and the prevalence varied according to
      study setting. Pain affected 27% of outpatients (range 8-85%), and 76% of
      patients cared for by palliative care services (range 63-88%). Pain was caused by
      cancer in 73% (range 44-87%), and cancer treatment in 11% (range 5-17%).
      Nociceptive pain was the major pathophysiological subtype in lung cancer pain,
      but neuropathic pain accounted for 30% (range 25-32%) of cases. CONCLUSIONS: The
      overall weighted mean pain prevalence of pain was 47% (range 6-100%). Cancer
      patients should be asked about pain at all stages of management. Those with pain
      should be investigated for disease progression and considered for referral for
      specialist management.

PMID- 15165084
TI  - Cigarette smoking and risk of large cell carcinoma of the lung: a case-control
      study in Uruguay.
AB  - In the time period 1988-2000, a case-control study on large cell carcinoma of the
      lung was conducted in Montevideo, Uruguay. The study included 149 cases (139 men
      and 10 women) and 596 controls (556 men and 40 women) afflicted with diseases not
      related with tobacco smoking. Cases and controls were frequency matched on age,
      sex, residence and urban/rural status. According to our results, large cell
      carcinoma was strongly related with cigarette smoking (OR for heavy smokers
      155.2, 95% CI: 30.6-786.1). Furthermore, all cases displayed higher risks for
      intensity compared with smoking duration. Smokers of black tobacco showed odds
      ratios (ORs) significantly higher than those presented by smokers of blond
      tobacco and smoking cessation displayed a reduction in risk of 95%, close to the
      risk of never smokers. Finally, filter use was not associated with any reduction
      in risk. It could be concluded that undifferentiated large cell carcinoma of the
      lung could be included among those lung tumors classified as Kreyberg I cancers.

PMID- 15165083
TI  - A novel approach for assessment of cancer predisposing roles of GSTM1 and GSTT1
      genes: use of putatively cancer resistant elderly tumor-free smokers as the
      referents.
AB  - We applied an alternative approach to assess the controversial evidence for the
      role of GSTM1 and GSTT1 deficiencies (null genotypes) in cancer susceptibility.
      In this study setting, the prevalence of GSTM1 and GSTT1 null genotypes in the
      lung cancer patients (LCs, n = 167) were compared with those in the group of
      putatively cancer resistant individuals, i.e. elderly tumor-free donors (EDs, n =
      324). Healthy middle-aged donors (HDs, n = 339) were used as another comparison
      group. Our results support the previous conclusions of a modest protective effect
      associated with presence of at least one functional copy of GSTM1 gene; the
      prevalence of GSTM1 deficiency in LCs (54%) did not differ from that observed in
      HDs (54%), but showed a significant increase when compared with EDs (45%) (OR =
      1.46, 95% CI = 1.00-2.12). Furthermore, in agreement with mechanistic
      considerations, the GSTM1 null genotypes were more prevalent in squamous cell
      carcinoma patients (58%) and in lung cancer patients with seemingly low
      cumulative carcinogen exposure dose (non-smokers: 63%; patients aged below 50
      years: 76%). Contrary to GSTM1, no significant effect in the lung cancer
      proneness was observed for the GSTT1 genotypes. The results of this study are
      thus in good agreement with the body of literature data, including several
      published meta-analyses. Consequently, the suggested study design involving
      additional "cancer resistant" group of non-affected subjects appears to provide
      highly demonstrative data and to be well suited for pilot investigations and for
      resolving controversial issues.

PMID- 15165085
TI  - Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin
      on human lung carcinoma cell lines.
AB  - Coumarin and 7-hydroxycoumarin have anti-tumour actions in vitro and in vivo.
      There are no previous reports on the cytostatic and apoptotic actions of coumarin
      and 7-hydroxycoumarin in non-small cell lung carcinoma (NSCLC) cell lines. Here
      we report on: (1) the inhibition of cell proliferation, (2) the phase in which
      cell cycle arrest occurs, and (3) the induction of apoptosis. Inhibition of cell
      proliferation was determined by 3H-thymidine incorporation. The effects on cell
      cycle phases were determined at 100 microg/ml of coumarin or 7-hydroxycoumarin
      using propidium iodide and flow cytometry. Higher concentrations were used to
      study apoptosis, detected by: (1) morphological cell changes, (2) subG1 peak
      detection and (3) Annexin-V assay. Peripheral blood mononuclear cells (PBMC)
      stimulated with phytohemagglutinin were used as controls. The actions of these
      compounds depended on drug concentrations and on histological cell type. Coumarin
      and 7-hydroxycoumarin inhibited cell growth by inducing cell cycle arrest in the
      G1 phase in all the lung carcinoma cell lines. Apoptosis required large
      concentrations of the coumarin compounds and was observed in adenocarcinomas.
      Apoptosis was not associated with intra-nucleosomal DNA fragmentation. Apoptosis
      was not observed in squamous lung carcinoma cell lines, but an increase in G1
      cell cycle arrest was detected. In PBMC, only large concentrations of the
      coumarin compounds elicited a cystostatic action. Coumarins in combination with
      other anti-neoplastic drugs might increase the effectiveness of NSCLC treatments.

PMID- 15165086
TI  - MDM2 gene amplification: a new independent factor of adverse prognosis in non
      small cell lung cancer (NSCLC).
AB  - The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC)
      remains unknown. In this study, we investigated the occurrence of MDM2
      amplification in surgically treated NSCLC patients. Molecular data were
      correlated with clinicopathological factors and evaluated for their prognostic
      value. The study group included 116 NSCLC patients who underwent pulmonary
      resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR
      using hybridization probe format on a LightCycler (Roche). The calculated ratio
      was a MDM2 value normalized to the amplification of the housekeeping gene
      phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan
      Meier method and compared with the use of the log-rank test. Multivariate
      analysis was based on Cox regression analysis. MDM2 amplification was found in 24
      patients (21%). There was no relationship between MDM2 amplification and
      clinicopathological factors, such as sex, age and stage of disease, pT, pN,
      histology and tumor differentiation. Median disease-free survival (DFS) in
      patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS
      24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival
      (OS) in patients with and without MDM2 amplification was 9 and 33 months,
      respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The
      strong prognostic relevance of MDM2 amplification for both DFS and OS was
      confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results
      suggest that MDM2 gene amplification analysis provides additional prognostic
      information in surgically treated NSCLC patients.

PMID- 15165087
TI  - Clinical course of lung cancer in patients with chronic kidney disease.
AB  - Co-morbidity has a major impact on survival in early and late-stage lung
      carcinoma. Patients maintained on dialysis are potentially at increased risk of
      cancer. However, since very few studies have examined the clinical course of lung
      cancer in patients with chronic kidney disease (CKD), we felt it was important to
      study the course of non-small cell lung cancer (NSCLC) and small cell lung cancer
      (SCLC) in this patient population. We performed a retrospective chart review of
      patients diagnosed with lung cancer and co-existent CKD. 107 patients (101 males
      and six females), with a mean age at diagnosis of 69 years (range: 39-86 years)
      were included in our study. Of these, 17 (15.9%) patients had SCLC while 87
      (81.3%) had NSCLC. Dyspnea, weight loss, and chest pain were the most common
      symptoms at presentation in our patient population occurring in 25, 20, and 15%
      of patients, respectively. The median survival of all the patients in the study
      was 10 months (range: 0-116 months). Patients with SCLC had a median survival of
      7 months. Patients with NSCLC had a median survival of 10 months. We found that
      the clinical course and survival in patients with lung cancer and CKD appear to
      be comparable to that of patients with lung cancer, but without kidney
      dysfunction. Hence though treatment of lung cancer does need to be individualized
      in the setting of CKD, it should not dissuade the clinician from treating the
      malignancy.

PMID- 15165088
TI  - Hypercalcemia-leukocytosis syndrome associated with lung cancer.
AB  - Hypercalcemia and leukocytosis are two of the most common paraneoplastic
      syndromes associated with various malignancies. Of note, concomitant
      manifestation of hypercalcemia and leukocytosis are occasionally observed in the
      same cancer patients. However, the relationship between these two paraneoplastic
      syndromes and clinical outcome is unclear. In the present study, we
      retrospectively investigated the occurrence of hypercalcemia (> or = 10.2 mg/dl
      after adjustment for serum albumin concentration), leukocytosis (> or =
      14,000/mm3 with no evidence of infection) or both in lung cancer patients (1149
      cases). There were 65 cases (5.7%) of hypercalcemia, 16 cases (1.4%) of
      leukocytosis and six cases (0.5%) of both hypercalcemia and leukocytosis at the
      time of first presentation. The occurrence of these two distinct paraneoplastic
      syndromes in the same patients was more frequent than could have been expected by
      chance alone (P < 0.001). There was a significant correlation between the
      hypercalcemia-leukocytosis syndrome and performance status (P = 0.002). Survivals
      of patients with hypercalcemia alone (median survival time: MST 3.8 months, n =
      59), leukocytosis alone (MST 1.9 months, n = 10), and the hypercalcemia
      leukocytosis syndrome (MST 1.5 months, n = 6) were significantly shorter than
      those without them (MST 9.5 months, n = 1074; P < 0.001). Moreover, survival of
      patients with the hypercalcemia-leukocytosis syndrome was significantly shorter
      than that of patients with hypercalcemia alone (P = 0.013). On the other hand,
      there was no significant difference in survival between the hypercalcemia
      leukocytosis syndrome and leukocytosis alone (P = 0.47). Multivariate analysis of
      prognostic factors using the Cox proportional hazards model could not demonstrate
      that the hypercalcemia-leukocytosis syndrome had independent prognostic
      significance. In conclusion, our results suggest that the hypercalcemia
      leukocytosis syndrome is an additional clinical entity of paraneoplastic syndrome
      and is an indicator for poorer outcome in lung cancer patients, although the
      frequency of the combined syndrome is very rare (0.5% of cases over a 10 year
      interval.

PMID- 15165089
TI  - A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy
      alone in stage III non-small cell lung cancer.
AB  - This study was designed to compare high-dose fractionated radiotherapy alone
      versus the same radiotherapy plus cisplatin in stage III non-small cell lung
      cancer (NSCLC). We randomly assigned 176 patients with stage III non-small cell
      lung cancer to one of two treatments; fractionated radiotherapy alone at dose of
      64 Gy for 6-7 weeks (2 Gy given 32 times, in five fractions a week) or
      radiotherapy in the same schedule, combined with 20mg/m2 cisplatin 1 h before
      radiotherapy, given on days 1-5 of the second and sixth treatment weeks. The
      frequency of loco-regional progression was 68% among the patients who received
      radiotherapy plus cisplatin and 86% among those who received radiotherapy alone
      (P = 0.0001). The probability of survival free of disease after 3 years was 10%
      among the patients assigned to radiotherapy plus cisplatin and 0% among those
      treated only with radiotherapy (P = 0.0006). Overall survival at 3 years was 10%
      among those given radiotherapy plus cisplatin and 2% among those who received
      radiotherapy alone (P = 0.00001). Multivariate analysis demonstrated that
      radiotherapy plus cisplatin significantly improved loco-regional progression-free
      survival and overall survival, irrespective of radiation dose. The addition of
      cisplatin to fractionated radiotherapy prolongs loco-regional progression-free
      interval and survival in stage III non-small cell lung cancer.

PMID- 15165091
TI  - Pleurodesis in recurrent pleural effusions: a randomized comparison of a
      classical and a currently popular drug.
AB  - STUDY OBJECTIVES: Pleurodesis is generally regarded to give the best palliation
      in recurrent pleural effusion. Talc is now increasingly recommended but in our
      department quinacrine has been used successfully for many decades with good
      results and only minor side effects. It was therefore decided to make a
      prospective randomized clinical study comparing quinacrine (500 mg) with talc (5
      g) with regard to efficacy and safety. METHODS: One hundred and ten eligible
      consecutive patients with recurrent and or malignant effusions, from 1 March 1996
      till 31 March 1999 were randomized to chemical pleurodesis with either talc or
      quinacrine through a chest drainage tube after medical thoracoscopy. Patients
      were evaluated with chest radiographs at 2 weeks and 2, 4, and 6 months after
      pleurodesis. RESULTS: Chi-square test showed 84% power to distinguish between the
      groups and 10% to determine the primary endpoint. Primary success (fluid
      production < 50ml/24h within the first 6 days) was 96% of 56 patients with talc
      and 91% of 54 patients with quinacrine, a non-significant difference (P = 0.46).
      Quinacrine patients needed a repeated treatment in 31% (17 patients) and talc
      patients in 7% (4 patients) (P < 0.05). Side effects were minor with no
      significant difference between the substances. CONCLUSIONS: Both substances are
      effective. Talc treatment had less often to be repeated. This indicates that the
      recommendation of talc for pleurodesis is well founded. However, quinacrine is a
      good alternative.

PMID- 15165090
TI  - Gefitinib as first-line, compassionate use therapy in patients with advanced non
      small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy of single-agent gefitinib (Iressa, ZD1839), an
      oral, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, as first
      line compassionate use therapy for advanced non-small-cell Lung cancer (NSCLC).
      PATIENTS AND METHODS: Twenty-five patients who were unfit or refused chemotherapy
      received oral gefitinib 250mg daily as first-line therapy for the treatment of
      recurrent or metastatic NSCLC in a compassionate use program at a single
      institution. RESULTS: Four of 22 evaluable patients (18%), two with
      adenocarcinomas and two with bronchioloalveolar carcinomas, had an objective
      response and five patients (23%) had stable disease. Duration of response or
      stable disease was 3.5-22+ months. Median time to progression was 2.2 months,
      median survival was 12.6 months and 1-year survival 52%. The partial response
      plus stable disease rate by Eastern Cooperative Oncology Group (ECOG) performance
      status (PS) was 4/5 for PS 0 patients; 3/6 for PS 1-2 patients; and 2/14 for PS 3
      4 patients. The two patients with PS > 2 who derived benefit from gefitinib had
      PS 3 due to co-morbidities. Two patients discontinued therapy due to severe
      toxicities: one patient had severe liver dysfunction and hemorrhagic cystitis,
      and another patient developed diarrhea with hypotension. A correlation between
      rash and antitumor activity was noted. Of seven patients who received
      chemotherapy subsequent to gefitinib, one had a partial response, three had
      stable disease, two progressed, and one was non-evaluable for response.
      CONCLUSION: We report encouraging response and survival results with gefitinib as
      first-line treatment in unselected patients with advanced NSCLC. Gefitinib
      monotherapy should undergo further evaluation as first-line therapy in advanced
      NSCLC.

PMID- 15165092
TI  - A multicenter phase II study of the combination of gemcitabine and docetaxel in
      previously treated patients with small cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of the combination of gemcitabine
      and docetaxel in pretreated patients with small-cell lung cancer (SCLC). PATIENTS
      AND METHODS: Twenty-two pretreated patients (median age 61 years, PS: 0-1 in 77%
      and 2 in 23%) with limited or extensive stage disease were treated with
      gemcitabine 1000 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8, every 21
      days. Fifteen (68%) of the 22 patients had received two prior regimens and
      fourteen (64%) were refractory to front-line chemotherapy. RESULTS: All patients
      were evaluable for efficacy analysis. No complete or partial responses were
      observed. Disease stabilization was obtained in one (5%) patient. The median
      survival was 14 weeks and the six-month survival rate was 28%. WHO grade 2 and 3
      toxicities were infrequent and easily manageable. CONCLUSION: The combination of
      gemcitabine and docetaxel was inactive as salvage treatment in this poor
      prognosis group of patients with SCLC.

PMID- 15165093
TI  - Phase I study of gemcitabine given weekly as a short infusion for non-small cell
      lung cancer: results and possible immune system-related mechanisms.
AB  - PURPOSE: To define the maximum tolerated dose (MTD) and the nature of the
      toxicities associated with gemcitabine given as a short infusion to patients with
      non-small cell lung cancer (NSCLC). Secondary objectives were to monitor
      immunologic response, clinical response, and survival. PATIENTS AND METHODS:
      Thirty-two patients diagnosed with advanced inoperable NSCLC and performance
      status of 0 or 1 participated in this study. Patients consisted of 22 males and
      10 females whose median age was 62 years (range 32-79). Gemcitabine was
      administered as a 30 min infusion once weekly for 3 weeks followed by 1 week of
      rest. Patients were enrolled at six gemcitabine dose levels ranging from 1000 to
      3500 mg/m2. Patients completed a median of four cycles (range 1-17). Responses
      were evaluated after every two cycles. RESULTS: Toxicity was evaluated in all 32
      patients. The MTD was not reached as gemcitabine was well tolerated at all dose
      levels. Grade 4 toxicity occurred in three (9%) patients: pulmonary and
      lymphocytopenia in one patient each, and both neurocortical and cardiac in one
      patient. Grade 3 toxicity was found in a total of 20 (63%) patients: pulmonary in
      10 (31%) patients; pain in 6 (19%) patients; liver toxicity in 6 (19%) patients;
      leukopenia and lymphocytopenia in 5 (16%) patients each; anemia, nausea, and
      cardiac toxicity in 3 (9%) patients each; proteinuria and infection in 2 (6%)
      patients each; and hemorrhage in 1 (3%) patient. Of the 29 patients evaluable for
      response, seven objective responses were achieved: six at the 2200 mg/m2 dose
      level and one at the 2800 mg/m2 dose level. The distribution of responses
      differed significantly by dose (P = 0.0124 by the exact chi-square test for
      independence). The overall response rate was 24.1% (95% CI, 10.3-43.5%). At 6 h
      post-infusion, there was a significant increase in spontaneous tumor necrosis
      factor (TNF) release and stimulated interleukin (IL)-2 production, and
      significant decreases in total white blood cell and lymphocyte counts (CD3+,
      CD8+, and CD16+ lymphocytes) and resting and stimulated superoxide production by
      formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate, and
      opsonized zymosan (OPS-Z). At 24 h post-infusion, there were significant
      decreases in total lymphocyte count, lymphocyte subsets (CD3+, CD4-, CD8+, CD56+,
      CD19+), and in resting and stimulated superoxide production by fMLP and OPS-Z.
      There also appeared to be an association between the levels of spontaneous TNF
      release and the severity of both gastrointestinal (GI) and pulmonary toxicities.
      CONCLUSION: Gemcitabine given as a short infusion was well tolerated at the dose
      levels of 1000-3500 mg/m2. The MTD was not reached. Toxicities appeared to be
      cumulative with multiple cycles. Gemcitabine appears to have activity against
      NSCLC. Although there was a differential dose-response rate among dose levels,
      increasing the gemcitabine dose beyond 2200mg/m2 did not show increased clinical
      response. Gemcitabine appears to modulate the immune response, which may in turn
      mediate both response and toxicity, although no statistically significant
      correlation between immune and clinical response was detected.

PMID- 15165094
TI  - Oral vinorelbine for the treatment of metastatic non-small cell lung cancer in
      elderly patients: a phase II trial of efficacy and toxicity.
AB  - PURPOSE: Before now oral vinorelbine has not yet been tested in a cohort of
      elderly, advanced non-small cell lung cancer patients, even though the
      intravenous form of this drug provides a reasonable therapeutic option for this
      group. This trial was conducted to determine the tumor response rate and toxicity
      profile of oral vinorelbine in advanced non-small cell lung cancer patients > or
      = 65 years of age. PATIENT AND METHODS: Fifty-eight evaluable patients > or = 65
      years of age with advanced non-small cell lung cancer were enrolled. Median age
      was 73 years (range: 65-87). The Eastern Cooperative Oncology Group (ECOG)
      performance score was 0, 1, or 2 in 29, 59, and 12% of patients, respectively.
      All patients had adequate organ function. Oral vinorelbine 60 mg/m2 per week was
      prescribed weekly as first-line therapy. RESULTS: Two patients manifested a
      confirmed tumor response, yielding a response rate of 3.4% (95% confidence
      interval (CI): 0.4, 11.9%). There were no complete responses. Median progression
      free survival was 3.5 months (95% CI: 2.2, 5.4 months), and median overall
      survival was 7.5 months (95% CI: 5.0, 12 months). There were five deaths, one of
      which might have been treatment-related, and there were 10 grade 4 events.
      CONCLUSIONS: Oral vinorelbine, as prescribed in this trial, provides minimal
      activity in the treatment of advanced non-small cell lung cancer in patients > or
      = 65 years of age.

PMID- 15165095
TI  - Regression of squamous cell carcinoma of the lung by Chinese herbal medicine: a
      case with an 8-year follow-up.
AB  - A 51-year-old woman diagnosed with squamous cell carcinoma (SCC) of the lung
      (T2N2M0) by cytological tests and a CT scan has survived for 8 years. During this
      period of time, she had been treated with Chinese herbal medicine alone for 4
      years. The herbal prescription consisted of nine Chinese medicinal herbs. These
      herbs have been reported to possess anti-tumour and immune enhancing effects.
      Therefore, it is suggested that the herbal treatment for this patient might have
      contributed to the complete regression of her lung carcinoma. Further research on
      the actions of these herbs is warranted.

PMID- 15165096
TI  - Caution! The latest AJCC's rules for lung cancer classification differ from the
      latest UICC's.

PMID- 15165097
TI  - Networking for excellence in lung cancer: paper vs research work.

PMID- 15165098
TI  - Severe acute interstitial pnuemonia and gefitinib.

PMID- 15165099
TI  - Is the second line data on the use of docetaxel in non-small cell lung cancer
      reproducible?

PMID- 15165100
TI  - Effect of gefitinib (ZD1839) on metastatic brain tumour.

PMID- 15165101
TI  - Outcomes of palliative chemotherapy in stage IV non-small cell lung cancer. Have
      we found what we are looking for?

PMID- 15165102
TI  - Response to de Gramont regimen in small cell lung cancer: a case report.

PMID- 15165103
TI  - Inhibition of expression of hypoxia-inducible factor-1alpha mRNA by nitric oxide
      in hypoxic pulmonary hypertension rats.
AB  - In order to study the effect of nitric oxide (NO) on the expression of hypoxia
      inducible factor-1 alpha (HIF-1alpha) mRNA in hypoxic pulmonary hypertension
      (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic
      control group, chronic hypoxic group and hypoxia plus L-arginine (L-Arg) group.
      The animal model of HPH was developed. The mean pulmonary arterial pressure
      (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The
      HIF-1alpha mRNA expression levels were detected by in situ hybridization (ISH)
      and semiquantitative RT-PCR. It was found that after 14 days hypoxia, the mPAP in
      normoxic control group (17.6 +/- 2.7 mmHg, 1 mmHg=0.133 kPa) was significantly
      lower than that in chronic hypoxic group (35.8 +/- 6.1 mmHg, t=0.2918, P<0.05)
      and mPAP in chronic hypoxic group was higher than that in hypoxia plus L-arginine
      group (24.4 +/- 3.8 mmHg, t=0.2563, P<0.05). ISH showed that the expression of
      HIF-1alpha mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic
      control group (0.1076 +/- 0.0205) was markedly weaker than that in chronic
      hypoxic group (0.3317 +/- 0.0683, t=3.125, P<0.05) and that in chronic hypoxic
      group was stronger than that in hypoxia plus L-arginine group (0.1928 +/- 0.0381,
      t=2.844, P<0.05). RT-PCR showed that the content of HIF-1alpha mRNA in chronic
      hypoxic group (2.5395 +/- 0.6449) was 2.16 times and 1.75 times higher than that
      in normoxic control group (1.1781 +/- 0.3628) and hypoxia plus L-arginine group
      (1.4511 +/- 0.3981), respectively. It is concluded that NO can reduce the mPAP by
      the inhibition of the expression of HIF-1alpha mRNA, which may be one of the
      mechanisms through which NO affects the pathogenesis of HPH.

PMID- 15165105
TI  - Effect of nuclear factor-kappaB on airway remodeling in asthmatic rats.
AB  - In order to investigate the effect of nuclear factor-kappaB (NF-kappaB) on airway
      remodeling in asthmatic rats, 18 Wistar rats were divided into three groups:
      asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were
      injected intraperitoneally with NF-kappaB specific inhibitor PDTC (100 mg/kg)
      before ovalbumin (OVA) challenge; control group. The NF-kappaB activity and the
      expression of inhibitory protein kappaBalpha (I-kappaBalpha) in airway were
      detected by electrophoretic mobility shift assay (EMSA), Western blot and
      immunohistochemistry respectively. The infiltration of inflammatory cells, the
      number of Goblet cells, the area of collagen and smooth muscle in airway were
      measured by means of image analysis system. The results showed that with the up
      regulation of airway NF-kappaB activity in asthmatic group, the number of goblet
      cells (3.084 +/- 0.86/100 microm basement membrane (BM)), the area of collagen
      (24.71 +/- 4.24 microm2/microm BM) and smooth muscle (13.81 +/- 2.11
      microm2/microm BM) in airway were significantly increased (P<0.05) as compared
      with control group (0.14 +/- 0.05/100 microm BM, 14.31 +/- 3.16 microm2/microm BM
      and 7.67 +/- 2.35 microm2/microm BM respectively) and PDTC group (0.33 +/-
      0.14/100 microm BM, 18.16 +/- 2.85 microm/microm BM and 8.95 +/- 2.16
      microm2/microm BM respectively). However, there was no significant difference
      between PDTC group and control group (P>0.05). It was concluded that the activity
      of NF-kappaB is increased in airway of asthmatic rats. Inhibition of NF-kappaB
      activation can attenuate constructional changes in asthma airway, suggesting NF
      kappaB may contribute to asthmatic airway remodeling.

PMID- 15165104
TI  - Effect of nuclear factor-kappa B on vascular endothelial growth factor mRNA
      expression of human pulmonary artery smooth muscle cells in hypoxia.
AB  - In order to investigate the effect of nuclear factor-kappa B (NF-kappaB) on
      vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary
      artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro
      were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF
      kappaB. The NF-kappaB p65 nuclei positive expression was detected by
      immunocytochemical technique. The IkappaBalpha protein expression was measured by
      Western blot. RT-PCR was used to detect the VEGF mRNA expression of HPASMCs. The
      results showed that no significant change was observed in the NF-kappaB p65
      nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but
      the levels of NF-kappaB p65 nuclei positive expression of cultured HPASMCs were
      significantly increased in hypoxia groups as compared with those in all normoxia
      groups (P<0.05). The IkappaBalpha protein expression of cultured HPASMCs showed
      no significant change during 6 h-24 h in normoxia, but significantly decreased in
      hypoxia as comapred with that in normoxia groups (P<0.05). PDTC (1 to 100
      micromol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration
      dependent manner in hypoxia. In conclusion, NF-kappaB can be partly translocation
      activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The
      inhibition of NF-kappaB activation can decrease the VEGF mRNA expression. It is
      suggested that the activation of NF-kappaB is involved in the VEGF mRNA
      expression of HPASMCs under hypoxia.

PMID- 15165106
TI  - Inhibitory effect of melatonin on the growth of H22 hepatocarcinoma cells by
      inducing apoptosis.
AB  - Whether melatonin not only inhibits the growth of H22 hepatocarcinoma cells but
      also induces apoptosis in vitro was assessed. The anti-proliferative effects of
      melatonin on tumor cells was observed by MTT assay and tumor cells growth curve
      assay. And the apoptosis of the cells was studied by acridine orange fluorescence
      assay and flow cytometry. The cell cycle of the tumor cells was also observed by
      flow cytometry. It was found that melatonin could significantly inhibit the
      growth of H22 hepatocarcinoma cells. Incubated with melatonin, chromatin
      condensation of the tumor cells was observed by fluorescence microscopy. Compared
      with control, the percentage of apoptotic cells was increased, and the proportion
      of G0/S increased but that of G2/M decreased. It was suggested that melatonin
      could directly inhibit the growth of H22 hepatocarcinoma cells by inducing
      apoptosis and extending the length of cell cycle of the tumor cells.

PMID- 15165108
TI  - Applied study on magnetic nanometer beads in preparation of genechip samples.
AB  - A protocol for enrichment and adsorption of karyocyte from whole blood by using
      magnetic nanometer beads as solid-phase absorbents was presented. The PCR
      amplification could be accomplished by using the nanobeads with karyocyte as
      template directly and the PCR products were applied on an oligonucleotide array
      to do gene typing. The HLA-A PCR amplification system and a small HLA-A
      oligonucleotide microarray were applied as the platform and an experiment
      protocol of separating karyocyte from whole blood using the magnetic nanometer
      beads (Fe2O3) were set up. The experimental conditions were also discussed. It
      showed that pH level of PBS eluent, Taq enzyme quantity and fragment length of
      products could influent the amplification results, and the magnetic nano-beads
      could succeed in sample preparation in microarray to provide a promising way in
      automatic detection and lab-on-a-chip.

PMID- 15165107
TI  - Cloning of the gene encoding urease subunit A in Helicobacter pylori.
AB  - The gene encoding urease subunit A (ureA) of Helicobacter pylori (H. pylori) was
      cloned from H. pylori isolate by polymerase chain reaction (PCR). Sterile
      distilled water instead of DNA served as negative control. The nucleotide
      sequence of the amplified product was determined. Homologous analysis of the ureA
      against that reported by Clayton CL and the GenBank and SwissProt databases were
      performed with the BLAST program at the Genome Net through the Internet. 0.8 kb
      PCR product was amplified from all H. pylori clinical isolators. The nucleotide
      sequence of the ureA was determined. The nucleotide sequence of the ureA began
      with ATG as the initiation codon and terminated in TAA as stop codon. The coding
      regions had a 44% G + C content. The DNA sequence was 98% homologous to that
      reported by Clayton CL (688 out of 702 residues were identical). The derived
      amino-acid sequences of the ureA were 99% homologous to that reported by Clayton
      CL (232 out of 234 residues were identical). The nucleotide sequence and the
      predicted protein showed significant homology to ureA of H. pylori in the NCBI
      Entrez database.

PMID- 15165109
TI  - Heat shock protein 70 gene polymorphisms in Han nationality of China with chronic
      obstructive pulmonary diseases.
AB  - In order to investigate whether polymorphism in gene for heat shock protein 70
      (HSP70) has any bearing on individual susceptibility to the development of
      chronic obstructive pulmonary disease (COPD), the geotypes of 88 patients with
      COPD and 87 healthy smoking control subjects were tested by polymerase chain
      reaction followed by restriction fragment polymorphism analysis for HSP70 gene.
      In COPD group, HSP70-1 genotype A/A, A/B and B/B was 59.1%, 35.2% and 5.7%, HSP70
      2 genotype A/A, A/B and B/B was 26.1%, 54.6% and 19.3%, and HSP70-hom genotype
      A/A, A/B and B/B was 70.4%, 27.3% and 2.3% respectively. In the control group, it
      was 60.9%, 27.5% and 3.5%, 20.7%, 56.3% and 23.0%, and 54.0%, 42.5% and 3.5%,
      respectively. The frequency of polymorphic genetypes showed no difference between
      the COPD group and the control group (P>0.05). It was suggested that geneic
      polymorphism in HSP70 is not associated with development of COPD in Han
      nationality of China.

PMID- 15165110
TI  - Expression of extracellular signal-regulated kinase and angiotensin-converting
      enzyme in human atria during atrial fibrillation.
AB  - In order to investigate the changes in the expression of extracellular signal
      regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the
      patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases
      were examined. Nineteen patients had chronic persistent AF (AF > or = 6 months,
      CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF.
      The ERK expression was detected at the mRNA level by reverse transcription
      polymerase chain reaction, at the protein level by Western blotting and at atrial
      tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE
      were determined by Western blotting techniques. The expression of ERK2-mRNA was
      increased in the patients with CAF (74 +/- 19 U vs sinus rhythm: 32 +/- 24 U, P <
      0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150% in the
      patients with AF compared to those with sinus rhythm. No significant difference
      between CAF and PAF was found. The expression of ACE was three-fold increased in
      the patients with CAF compared to those with sinus rhythm. Patients with AF
      showed an increased expression of ERK1/ERK2 in atrial interstitial cells and
      marked atrial fibrosis. An ACE-dependent increase in the amounts of activated
      ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the
      development of atrial fibrosis in the patients with AF. These findings may have
      important impact on the treatment of AF.

PMID- 15165111
TI  - Effect of autonomic nervous system on the transmural dispersion of ventricular
      repolarization in intact canine.
AB  - The effect of the autonomic nerves on the transmural dispersion of ventricular
      repolarization in intact canine was investigated. By using the monophasic action
      potential (MAP) recording technique, monophasic action potentials (MAPs) of the
      epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded
      simultaneously by specially designed plunge-needle electrodes at the left
      ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of
      repolarization among three myocardial layers as well as the incidence of the EAD
      before autonomic nervous stimulation and during autonomic nervous stimulation
      were compared. The results showed that the MAPD90 of Epi, Mid and Endo before
      autonomic nervous stimulation were 278 +/- 11 ms, 316 +/- 16 ms and 270 +/- 12 ms
      respectively, the MAPD90 of Mid was significantly longer than that of Epi or Endo
      (P<0.01). MAPD90 of Epi, Mid and Endo were shortened by 19 +/- 4 ms, 45 +/- 6 ms,
      18 +/- 3 ms respectively during sympathetic stimulation. Compared with that of
      the control, the transmural dispersion of repolarization during sympathetic
      stimulation was shortened from 44 +/- 4 ms to 15 +/- 3 ms (P<0.01), but early
      afterdepolarizations were elicited in the Mid of 5 dogs (41%) during sympathetic
      stimulation. Parasympathetic stimulation did not significantly affect the MAPD90
      in the three layers. It is concluded that there is the transmural dispersion of
      ventricular repolarization in intact canine. Sympathetic stimulation can reduce
      transmural dispersion of repolarization, but it can produce early
      afterdepolarizations in the Mid. Parasympathetic stimulation does not
      significantly affect the transmural dispersion of ventricular repolarization.

PMID- 15165112
TI  - Effects of POH in combination with STI571 on the proliferation and apoptosis of
      K562 cells.
AB  - The effects of monoterpene perilly alcohol (POH) alone or in combination with
      STI571 on the proliferation and apoptosis of the cell line K562 positive for
      Bcr/Abl were investigated. By using cell culture, the effect of the drugs on the
      proliferation of the cells was studied. TUNEL and flow cytometry assay of FITC
      Annexin V and PI labeled cells were applied to detect the effects of the drugs on
      the apoptosis of the cells. The results showed that at 36 h, IC50 of POH on K562
      positive for Bcr/Abl and HL-60 negative for Bcr/Abl were 81.0 +/- 11.3 micromol/L
      and 113.6 +/- 23.4 micromol/L respectively (P>0.05). POH could inhibit the
      proliferation of K562 in a time- and dose-dependent manner with the inhibitory
      rate of 100 micromol/L POH on K562 cells at 36 h being (53.2 +/- 3.65)%. K562
      cells were more sensitive to STI571 than POH. IC50 of STI571 on K562 cells in 36
      h was (0.256 +/- 0.054) micromol/L. In a time- and dose-dependent manner, POH
      induced the apoptosis of K562 cells with the percentage of apoptotic cells by 100
      micromol/L POH at 40 h being (21.0 +/- 3.3)%. Both 100 micromo/L POH and 0.2
      micromol/L STI571 had the same inhibitory effects on the K562 cells at 36 h. But
      at 12 and 24 h, the inhibitory rate of POH was significantly higher than that of
      STI571 (P<0.05) and the ability of STI571 inducing apoptosis at 36 h was greater
      than that of POH. 50 micromol/L, 100 micromol/L and 200 micromol/L POH in
      combination with 0.2 micromol/L STI571 could obviously increase the inhibitory
      effects on the cellular proliferation. Combined use of 50 micromol/L, 100
      micromol/L, 200 micromol/L with 0.2 micromol/L STI571 could strongly induced
      apoptosis, especially 200 micromol/L POH in combination with 0.2 micromol/L
      STI571. It was concluded that the antileukemia effect of POH had no obvious
      Bcr/Abl positive selectivity. POH can inhibit the proliferation of K562 and
      induce the apoptosis in a time- and dose-dependent manner. K562 cells were more
      sensitive to STI571 than POH. POH in combination with STI571 could obviously
      enhance the abilities of STI571 inhibiting the proliferation and inducing
      apoptosis of K562 cells.

PMID- 15165113
TI  - Role of extracelluar regulated protein kinases in FTY720-induced apoptosis of
      leukemia cell lines HL-60 and U937.
AB  - The effects of a novel immunosuppressive agent FTY720 on proliferation inhibition
      and apoptosis of acute leukemia cell lines HL-60 and U937, and the role of
      extracelluar regulated protein kinase (ERK) in the course of proliferation
      inhibition and apoptosis induced by FTY720 were studied. The proliferation
      inhibition rate of HL-60 and U937 cells by various concentrations of FTY720 was
      detected by MTT assay. Cell apoptosis was detected by DNA fragment analysis and
      flow cytometry. The phosphorylated ERK1/2 protein expression was observed by
      Western blotting. The change of intracellular distribution of ERK1/2 protein was
      identified by SP immunohistochemical staining. The results showed that FTY720
      could inhibit the growth of HL-60 and U937 cells effectively in a dose-dependent
      manner. After incubation with FTY720 for 24 h, apoptosis was observed in HL-60
      and U937 cells. The intracellular expression of phosphorylated ERK1/2 protein was
      also down-regulated and the distribution of ERK1/2 protein in cell nuclear was
      reduced during FTY720-induced apoptosis. So, that FTY720 inhibited ERK1/2
      phosphorylation might mediate the role of FTY720-induced apoptosis and
      proliferation inhibition of leukemia cells.

PMID- 15165114
TI  - Detection of telomerase activity and the expression of telomerase subunits in the
      patients with acute myelogenous leukaemia.
AB  - Telomerase activity and the expression of telomerase subunits (for example,
      telomerase reverse transcriptase and telomerase associated protein 1 and
      telomerase RNA component) of peripheral white blood cells were detected in the
      patients with acute myelogenous leukaemia (AML) and the correlation between
      telomerase activity and the expression of telomerase subunits was observed. In 94
      peripheral white blood cells from 18 healthy volunteers and 76 patients with AML,
      including 31 AML at initial presentation, 24 at relapse and 21 at complete
      remission, the telomerase activity and telomerase subunits mRNA or RNA were
      detected by PCR-ELISA and RT-PCR respectively. The results showed that the
      positive rate of telomerase from patients with AML at initial presentation, at
      relapse and at complete remission was 74.1%, 79.2% and 4.8% respectively. The
      positive rate of telomerase reverse transcriptase mRNA from healthy volunteers,
      AML at initial presentation, AML at relapse and AML at complete remission was
      5.6%, 80.6%, 83.3% and 9.5% respectively. The positive rate of telomerase
      associated protein 1 mRNA and telomerase RNA component in all samples were 100%.
      It was suggested that the up-regulation of telomerase activity and the expression
      of telomerase reverse transcriptase is correlated closely with the occurrence and
      relapse of AML, so telomerase activity and the expression of telomerase reverse
      transcriptase may be used to estimate the curative effect and predict relapse of
      AML. Moreover, the up-regulation of telomerase activity is correlated with the
      expression of telomerase reverse transcriptase significantly.

PMID- 15165115
TI  - Construction and significance of directional expression cDNA library from human
      NB4 cells.
AB  - Human acute premyeloid leukemia cell cDNA expression library was constructed to
      screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were
      extracted from human premyeloid cell line NB4. First and second strands of cDNA
      were synthesized by reverse transcription. After blunting, the cDNA fragments
      were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and
      less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the
      remaining were ligated with lambdaZAP vector. The recombinants were packaged in
      vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue
      MRF' for titration. The recombinants were examined by color selection. In order
      to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV
      phagemid was excised from the ZAP express vector by using ExAssist helper phage
      with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR
      I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x
      10(6) recombinant bacteriophages was constructed with the recombinant ratio of
      99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb.
      It was concluded that the constructed cDNA library are deserved to screen target
      clones.

PMID- 15165116
TI  - Growth-inhibitory effects of curcumin on ovary cancer cells and its mechanisms.
AB  - To study the growth-inhibitory effects of curcumin on human ovary cancer A2780
      cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780
      cancer cells, after being treated with 10 micromol/L-50 micromol/L curcumin for 6
      24 h, were examined by MTT method. The morphological changes of cancer cells were
      observed under inversion microscopy. Cellular apoptotic rates were determined by
      using TUNEL. The protein expression levels of bcl-2, p53 and MDM2 in cancer cells
      were examined by SP immunohistochemistry. After being treated by various
      concentrations of curcumin, the growth of cancer cells was inhibited
      significantly. Some cancer cells presented characteristic morphological changes
      of apoptosis. The rates of apoptosis were 6.41%-28.48% (P<0.01). The expression
      of bcl-2 and p53 was decreased, which depended on the action time (P<0.01). There
      were no obvious changes in MDM2 expression. It was concluded that curcumin could
      significantly inhibit the growth of ovary cancer cells. The induction of
      apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of
      its molecular mechanisms.

PMID- 15165117
TI  - Application of fetal DNA in maternal plasma in noninvasive prenatal diagnosis.
AB  - To explore the application of fetal DNA in maternal plasma for noninvasive
      prenatal diagnosis, the DNA template was extracted by hydroxybenzene-chloroform
      from 44 maternal (7-41 weeks) plasma. The Fetus-derived Y sequence DYZ-1 gene
      (149bp) was chosen to be amplified by PCR. The fragment was identified in all the
      plasma of male bearing pregnant women with the diagnostic accordance rate being
      100.00%. Two of the 22 female bearing pregnant women had false positive results.
      Among the 44 pregnant women, the diagnostic accordance rate was 88.89% at early
      pregnant stage, 100.00% at medium pregnant stage, and 96.55% at late stage
      respectively. The final accuracy of 95.45% was obtained in all cases. It was
      concluded that by means of hydroxybenzene-chloroform extraction the authors of
      this article promoted the concentration and purity of the DNA template, and
      diagnosed more accurately. The results showed that free fetal DNA in the maternal
      plasma could be regarded as the gene resource for noninvasive prenatal diagnosis.

PMID- 15165118
TI  - Dysregulation of the TGF-beta postreceptor signaling pathway in cell lines
      derived from primary or metastatic ovarian cancer.
AB  - Transforming growth factor-beta (TGF-beta) may cause cell cycle arrest, terminal
      differentiation, or apoptosis in most normal epithelial cells, whereas most
      malignant cell lines are resistant to TGF-beta. Mechanisms of resistance to TGF
      beta caused by modulation of cell cycle regulators and/or inactivation of
      components of the TGF-beta signaling transduction pathway such as C-myc and Smad4
      are not well understood. To investigate the potential association between loss of
      sensitivity to TGF-beta and expression status of transforming growth factor
      receptor II (TbetaR II) , Smad4, CDC25A and C-myc in 14 cell lines derived from
      ovarian cancer, the expression levels of these genes were detected by semi
      quantitative RT-PCR. Normal ovarian surface tissues were used as controls. The
      expression of TbetaR II was detectable in all of 14 cell lines. The expression of
      Smad4 was decreased in 10 cell lines and 9 cell lines overexpressed CDC25A, as
      compared to normal controls. CDC25A gene was overexpressed with 88% (8/9) in
      tumorigenic cell lines as determined by xenografts in nude mice, and only in 20%
      (1/5) of non-tumorigenic cell lines (P<0.05). C-myc was not overexpressed in any
      of these cell lines. The loss of sensitivity to TGF-beta of cell lines derived
      from ovarian cancers may be related to a decreased expression of Smad4, which
      mediates TGF-beta induced growth inhibition, and/or an overexpression of CDC25A.
      This overexpression of CDC25A correlates with increased tumorigenicity of ovarian
      cancer cell lines. The loss of sensitivity to TGF-beta is not associated with a
      lack of TbetaR II.

PMID- 15165119
TI  - Noninvasive prenatal diagnosis of fetal sex by single-cell PEP-PCR method.
AB  - A new method for noninvasive prenatal diagnosis of fetal sex was developed by
      using single-cell PEP-PCR techniques. Micromamipulation techniques were used to
      obtain single fetal cells from 273 maternal blood samples. The genome of single
      cells was preamplified by PEP and SRY genes were analyzed by PCR method. The SRY
      genes of 149 samples were detected by the new method among 153 samples carrying
      male fetus, while 119 out of 120 samples carrying female fetus were proved
      negative for SRY genes. The sensitivity and specificity of the new method were
      97.39% and 99.17% respectively and the correct rate was 98.17%. The new method
      has the advantage of high sensitivity and specificity in noninvasive prenatal
      diagnosis of fetal sex and provides the basis of other researches such as sex
      linked inherited diseases.

PMID- 15165120
TI  - Correlation between blood cAMP, cGMP levels and traumatic severity in the
      patients with acute trauma and its clinical significance.
AB  - In order to investigate the correlation between traumatic servity and blood cAMP
      and cGMP levels in the patients with acute trauma and its clinical significance,
      120 cases of trauma were randomly selected and divided into 4 groups (n = 30 in
      each group): mildly traumatic group (ISS < or = 9), moderately traumatic group
      (ISS = 10-16), severely traumatic group (ISS = 17-25) and dangerously traumatic
      group (> 25). The cAMP and cGMP levels were assayed in sera, leucocytes and
      platelets respectively in 6 h and 24 h after trauma. The results showed that cAMP
      and cGMP levels were elevated significantly in sera and platelets (P < 0.05 or P
      < 0.01), meanwhile cGMP levels in leucocytes (P < 0.05). It was concluded that
      cAMP and cGMP might play an important role in traumatic stress, participate in
      the cellular signal transducation and promote the immune function of leucocytes
      and the coagulation founction of platelets. Serum cAMP and cGMP levels were
      upregulated correspondingly as ISS increased, and positively correlated to the
      traumatic severity.

PMID- 15165121
TI  - Protective effect of interleukin-1beta on motor neurons after sciatic nerve
      injury in rats.
AB  - Protective effect of interleukin-1beta (IL-1beta) on motor neurons was studied
      after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups
      randomly. The right sciatic nerve of each rat was resected. After silicon
      tubulization of sciatic nerve in rat, 15 microl 1 ng/ml IL-1beta and PBS solution
      were injected into the silicon capsule respectively. Enzyme histochemistry was
      performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS)
      activity of spinal alpha motor neurons in spinal segments 2 weeks later. Neurons
      were counted and the diameter and cross sectional (c/s) area of neurons were
      analyzed by using computer image analysis system. The results showed that as
      compared with the normal side, both enzyme activities significantly changed in
      motor neurons in PBS group. The diameter and c/s area of both neurons changed
      significantly too (P < 0.01). These results suggest that exogenous IL-1beta
      protects alpha-motor neurons from degeneration and necrosis after peripheral
      nerve injury.

PMID- 15165122
TI  - Isolation, culture and identification of neural stem cells in new-born rats.
AB  - The cortexes were obtained from new-born rats and dissociated to single cells by
      triturating. The cells were cultured in neural stem cell (NSC) culture medium
      (DMEM supplemented with bFGF, EGF and B27) and formed primary neurospheres after
      7 days. Single cells dissociated from neurosphere were cultured in 96-well plates
      and formed single-cell cloning neurosphere 7 days later. The primary and single
      cell cloning neurospheres were both positive for the immunofluorescent staining
      of nestin and were identified as NSC. It was proved that NSC can be expanded in
      vitro and provide seed cells for neural tissue engineering.

PMID- 15165123
TI  - Involvement of apoptosis in 3-nitropropionic acid-induced ischemic tolerance to
      transient focal cerebral ischemia in rats.
AB  - The involvement of apoptosis in mitochondrial toxin 3-nitropropionic acid (3-NPA)
      induced ischemic tolerance to transient focal cerebral ischemia in rats and the
      mechanism was investigated. 3-NPA at a dose of 20 mg/kg or vehicle control was
      intraperitoneally into the rats. Three days later, rats were exposed to 2 h of
      middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes
      were assessed by 2,3,5-triphenyltetrazolinm chloride (TTC) staining 24 h after
      reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end
      labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as
      compared to the vehicle-treated group, pretreatment with 3-NPA could reduce the
      infarct volume by 23.3% and decrease the number of TUNEL-positive neural cells
      and apoptotic percentage by 47% (P<0.05) and 44.9% (P<0.01), respectively. It was
      concluded that the development of 3-NPA-induced ischemic tolerance in brain might
      be related to the decreases in neural cell apoptosis.

PMID- 15165124
TI  - LPS-induced degeneration of dopaminergic neurons of substantia nigra in rats.
AB  - In order to investigate the neurotoxicity of lipopolysaccharide (LPS) on the
      dopaminergic neurons of substantia nigra and the pathogenesis of Parkinson
      disease, LPS was stereotaxically infused into substantia nigra (SN). At different
      dosages and different time points with 5 microg LPS, the damage of the
      dopaminergic neurons in SN was observed by using tyrosine-hydroxylase (TH)
      immunohistochemical staining. The results showed that 14 days after injection of
      0.1 microg to 10 microg LPS into the rat SN, TH-positive (TH+) neurons in the SN
      were decreased by 5%, 15%, 20%, 45 %, 96% and 99% respectively. After injection
      of 5 microg LPS, as compared with the control groups, TH+ neurons began to
      decrease at 3rd day and obviously decrease at 14th day, only 5% of total cells,
      and almost disappeared 30 days later. The results suggested that LPS could induce
      the degeneration of dopaminergic neurons in the SN in a dose- and time-dependent
      manner.

PMID- 15165125
TI  - Apoptosis of human trabecular meshwork cells induced by transforming growth
      factor-beta2 in vitro.
AB  - Whether transforming growth factor-beta2 (TGF-beta2) induces apoptosis of human
      trabecular meshwork cells was investigated in vitro. Cultured 3-5 passage human
      trabecular meshwork cells were treated with 0 (control), 0.32, 1, 3.2 ng/ml TGF
      beta2 for 48 h and divided into control group and experimental group. The
      apoptosis of human trabecular meshwork cells was examined by transmission
      electron microscopy, TUNEL technique and flow cytometry. The results showed
      characteristic morphologic changes of apoptotic cells were observed under
      transmission electron microscopy. DNA fragmentation of human trabecular meshwork
      cells was found by TUNEL technique. Quantitative analysis of flow cytometry
      showed that percentages of apoptotic human trabecular meshwork cells were (2.79
      +/- 0.44)%, (4.43 +/- 1.17)% and (9.60 +/- 2.05)% respectively with different
      concentrations [1 ng/ml (P<0.05), 3.2 ng/ml (P<0.01)] of TGF-beta2 with the
      difference being significant between experimental group and control group [(1.41
      +/- 0.34)%]. It was concluded that TGF-beta2 can induce apoptosis of human
      trabecular meshwork cells in vitro and may be involved in the decrease of
      trabecular meshwork cells in the patients with primary open angle glaucoma and
      aging of normal people.

PMID- 15165127
TI  - Management of mandibular hypoplasia using distraction osteogenesis technique.
AB  - By using distraction osteogenesis technique, 3 cases of mandibular hypoplasia
      were treated by home-made and German-made jaw distractors: including one patient
      suffered from bilateral ankylosis of temporo-mandibular joint and 2 patients from
      deficiency of mandible. The duration of distraction osteogenesis was one month.
      The bone distractor was removed 3 months after operation. Satisfactory results
      were obtained in all 3 cases. Distraction osteogenesis can successfully be used
      in mandibular functional reconstruction and has much more advantages than
      traditional technique.

PMID- 15165126
TI  - Correlation between the expression of Fas, Bcl-2 in peripheral blood lymphocytes
      and the level of IFN-gamma, IL-4 in serum of patients with condyloma acuminata.
AB  - In order to investigate the correlation between the expression of the apoptotic
      regulatory proteins (Fas, Bcl-2) in peripheral blood lymphocytes (PBLC) and the
      level of IFN-gamma and IL-4 in serum of the patients with condyloma acuminata
      (CA) in the immune pathogenesis of CA, indirect immunofluorescence labeling
      method of flow cytometer and solid sandwich ELISA method were performed for
      detecting the expression of Fas, Bcl-2 in PBLC and the level of IFN-gamma and IL
      4 in serum of 60 cases of CA. The results showed the expression level of Fas in
      PBLC of CA was significantly higher than in the normal control group, but the
      expression level of Bcl-2 was significantly lower (both P<0.01). The level of IFN
      gamma in serum of CA was significantly lower than in the normal control group
      (P<0.01), but IL-4 was significantly lower (both P<0.01). The expression of Fas
      in PBLC had a negative correlation with the level of IFN-gamma in serum of
      patients with CA, but had a positive correlation with the level of IL-4; The
      expression of Bcl-2 had a positive correlation with the level of IFN-gamma, but
      had a negative correlation with the level of IL-4. All the correlation
      coefficients had significant difference by t test (P<0.01). It was suggested
      abnormal apoptosis in PBLC, the suppressed secretion of the TH1-associated
      cytokines (eg: IFN-gamma) and the increased secretion of the TH2-associated
      cytokines (eg: IL-4) existed in the patients with CA and might play an important
      role in the immune pathogenesis of CA.

PMID- 15165128
TI  - Evaluation of large intracranial aneurysms with cine MRA and 3D contrast-enhanced
      MRA.
AB  - The value of combined application of both ECG-gated cine MRA and 3D-CEMRA in the
      detection of large intracranial aneurysms was evaluated and the findings were
      compared with those of conventional MRA and DSA. Twenty-four patients with 26
      large intracranial aneurysms underwent MRI and DSA. All these aneurysms, diameter
      from 15 to 39 mm, were located at internal cerebral artery (n=12), vertebral
      artery (n=3), basilar artery (n=4), anterior cerebral artery (n=2), middle
      cerebral artery (n=2), anterior communicate artery (n=2) and posterior
      communicate artery (n=1). Thirteen cases of hematoma or cavernoma were studied as
      control group. All patients were examined on GE 1.5T MR system. ECG-gated cine
      MRA was performed with 2D multi-phase fast gradient-recalled echo sequence in a
      single section. All the images were analyzed with signal intensity VS time curve
      for differentiating intraaneurysmal blood flow from static tissue. The results
      were analyzed by statistic "t" test. 3D-CEMRA was performed with spoiled gradient
      recalled echo and one dose of Gd-DTPA. All data was processed with multi-plannar
      reformat (MPR) and tomography for the demonstration of aneurysms in detail. All
      26 aneurysms were demonstrated successfully by combined application of both cine
      MRA and 3D-CEMRA. Compared to DSA and conventional 3D-MOTSA, its sensitivity and
      specificity figures were both 100%. Cine MRA could differentiate the blood flow
      from the static tissue. The intensity VS time curves of intraaneurysmal blood
      flow offered fluctuating form and average signal change between systole and
      diastole period was about 89.8 +/- 37.4; However, under the control group,
      intraaneurysmal thrombus or cerebral hemorrhage or cavernomas had no significant
      signal change and the curves offered steady form with the average signal change
      being about 8.2 +/- 6.3. There was statistically significant difference between
      the intraaneurysmal blood flow and static tissue (P=0.025, <0.05). 3D-CEMRA was
      very useful in demonstrating the aneurysmal size, intraaneurysmal thrombus
      formation, neck and the detailed relationship of the aneurysm to the surrounding
      structures. It was concluded that the combined application of both cine MRA and
      3D-CEMRA might be a valuable clinical tool for the detection of large
      intracranial aneurysms.

PMID- 15165129
TI  - MRI features of intracranial primitive neuroectodermal tumors in adults:
      comparing with histopathological findings.
AB  - The MRI appearances of 7 adult patients with pathologically proven intracranial
      primitive neuroectodermal tumors (PNET) were retrospectively analyzed. The MRI
      features were compared with findings in pathology and surgery. In this group, the
      tumor masses were most commonly found in the semisphere of cerebrum and in the
      vermis of cerebellum. They were relatively large and 4 were in lobulated shape.
      All of them had well-defined margins. MR images showed the tumors to be mildly or
      obviously hypointense on T1-weighted images and hyperintense on T2-weighted
      images. Most masses had heterogeneous appearances with some cystic and necrotic
      areas. Intratumoral haemorrhage and focal calcification were occasionally seen.
      Mostly, there was no or only mild surrounding edema. Marked inhomogeneous
      contrast enhancement on MRI was seen in 6 cases except one. Two patients with
      multiple intracranial metastases were revealed on MR images. In this series,
      there was good correlation between MRI features and findings in pathology and
      surgery. These results showed that certain MRI features might suggest the
      diagnosis of intracranial PNET in adults. MRI is an effective technique to detect
      these tumors and is helpful to treatment planning and follow-up.

PMID- 15165130
TI  - Quantitative analysis on economic contribution of community health service in
      China.
AB  - In China, the implementation of community health service shows that the
      prevention is an essential and important part of our national health system and
      is helpful to decrease the medical expenditure gradually. According to the data
      from Health Statistic Information Center of Ministry of Health in China, we
      calculated that the total health expenditure of China would be decreased 8000.0
      million yuan only in 2001, among which, 1188.3 million, 1953.9 million and 4833.0
      million yuan were respectively saved for the government budget, the society and
      resident if implementing the policy of community health service powerfully. And
      every outpatient can save 15.46 yuan per time. By the quantitative analysis on
      the economic contribution of community health service, it can be proved that a
      great economic benefit could be gotten from the implementation of community
      health service.

PMID- 15165131
TI  - Ancistrotanzanine C and related 5,1'- and 7,3'-coupled naphthylisoquinoline
      alkaloids from Ancistrocladus tanzaniensis.
AB  - Three new naphthylisoquinoline alkaloids, the 7,3'-coupled ancistrotanzanine C
      (6), the 5,1'-coupled O-methylancistrocladinine (7), and the likewise 5,1'
      coupled O,N-dimethylancistrocladine (8, previously known only as a partial
      synthetic compound), have been isolated from the highland liana Ancistrocladus
      tanzaniensis, along with the two known 7,3'-coupled naphthylisoquinoline
      alkaloids ancistrocladidine (4) and ancistrotectorine (5). All of the compounds
      are S-configured at C-3 and bear an oxygen at C-6, and thus belong to the so
      called Ancistrocladaceae type, similar to 1-3 previously isolated from this newly
      discovered plant species. The structural elucidation was achieved by chemical,
      spectroscopic, and chiroptical methods. The biological activities of the
      alkaloids against the pathogens causing malaria tropica, leishmaniasis, Chagas'
      disease, and African sleeping sickness were evaluated.

PMID- 15165132
TI  - Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide:
      preparation and biological activity.
AB  - A series of seven synthetic discodermolide analogues 2-8, which are minor side
      products generated during the final stages in the synthesis of (+)-discodermolide
      (1), have been purified and evaluated for in vitro cytotoxicity against A549,
      P388, MFC-7, NCI/ADR, PANC-1, and VERO cell lines. These synthetic analogues
      showed a significant variation of cytotoxicity and confirmed the importance of
      the C-7 hydroxy through C-17 hydroxy molecular fragment for potency.
      Specifically, these analogues suggested the relevance of the C-11 hydroxyl group,
      the C-13 double bond, and the C-16 (S) stereochemistry for the potency of (+)
      discodermolide. The preparation, purification, structure elucidation, and
      biological activity of these new analogues are described.

PMID- 15165133
TI  - New isoprenylated flavones, artochamins A--E, and cytotoxic principles from
      Artocarpus chama.
AB  - Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known
      flavones (6-13), were isolated from the roots of Artocarpus chama. All structures
      were elucidated by spectroscopic methods. Artonin E (12) showed strong
      cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast
      adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231
      (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent
      against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB
      (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN)
      variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects
      compared with 3 and 12.

PMID- 15165134
TI  - Chemical constituents from the mangrove plant, Aegiceras corniculatum.
AB  - From the stems and twigs of the mangrove plant, Aegiceras corniculatum, seven new
      compounds, namely, 2-methoxy-3-nonylresorcinol (1), 5-O-ethylembelin (2), 2-O
      acetyl-5-O-methylembelin (3), 3,7-dihydroxy-2,5-diundecylnaphthoquinone (4), 2,7
      dihydroxy-8-methoxy-3,6-diundecyldibenzofuran-1,4-dione (5), 2,8-dihydroxy-7
      methoxy-3,9-diundecyldibenzofuran-1,4-dione (6), and 10-hydroxy-4-O-methyl-2,11
      diundecylgomphilactone (7), were isolated together with three known compounds, 5
      O-methylembelin (8), 3-undecylresorcinol, and 2-dehydroxy-5-O-methylembelin. The
      structures of 1-7 were determined by spectroscopic methods. Compound 2 and 5-O
      methylembelin showed in vitro cytotoxicity against the HL-60, Bel(7402), U937,
      and Hela cell lines.

PMID- 15165136
TI  - A new antimalarial quassinoid from Simaba orinocensis.
AB  - A new antimalarial quassinoid, namely, orinocinolide (1), was isolated from the
      root bark of Simaba orinocensis, together with the previously reported
      simalikalactone D (2). The structure of 1 was determined primarily from 1D and 2D
      NMR analysis, as well as by chemical derivatization. Compound 1 was found to be
      as equally potent as 2 against Plasmodium falciparum clones D6 and W2 (IC(50)
      3.27 and 8.53 ng/mL vs 3.0 and 3.67 ng/mL, respectively), but was 4- and 28-fold
      less toxic than 2 against VERO cells (IC(50) 10 vs 2.3 microg/mL) and HL-60
      (IC(50) 0.7 vs 0.025 microg/mL), respectively. In addition, 2 was >46- and >31
      fold more potent than pentamidine and amphotericin B (IC(50) 0.035 vs 1.6 and 1.1
      microg/mL) against Leishmania donovani, while 1 was inactive. Orinocinolide (1)
      inhibited growth of human cancer cells SK-MEL, KB, BT-549, and SK-OV-3, but was
      less potent than 2 (IC(50) 0.8-1.9 vs 0.3-1.0 microg/mL) against these cells.

PMID- 15165135
TI  - Molecular-targeted antitumor agents: the Saururus cernuus dineolignans
      manassantin B and 4-O-demethylmanassantin B are potent inhibitors of hypoxia
      activated HIF-1.
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of
      tumor cell adaptation and survival under hypoxic conditions. Selective HIF-1
      inhibitors represent an important new class of potential molecular-targeted
      antitumor therapeutic agents. Extracts of plants and marine organisms were
      evaluated using a T47D human breast tumor cell-based reporter assay for HIF-1
      inhibitors. Bioassay-guided fractionation of the lipid extract of Saururus
      cernuus resulted in the isolation of manassantin B (1) and a new compound, 4-O
      demethylmanassantin B (2). The structure of 2 was determined spectroscopically.
      The absolute configurations of manassantin-type dineolignans have not been
      previously reported. Therefore, the absolute configurations of the chiral centers
      in each side chain were deduced from spectroscopic analysis of the Mosher MTPA
      ester derivatives of 1. Both 1 and 2 are among the most potent small molecule HIF
      1 inhibitors discovered, to date, with IC(50) values of 3 and 30 nM,
      respectively. Compounds 1 and 2 selectively inhibited hypoxia-activated HIF-1 in
      contrast to iron chelator-activated HIF-1. Compounds 1 and 2 also inhibited
      hypoxic induction of the angiogenic factor VEGF. Further study revealed that 1
      selectively blocked the induction of HIF-1alpha protein, the oxygen regulated HIF
      1 subunit that determines HIF-1 activity.

PMID- 15165137
TI  - 5-methylcoumaranones from Mutisia friesiana and their bioactivity.
AB  - In addition to the known mutisicoumaranones A (1) and B (2), the methanolic
      extract of the aerial parts of the shrub Mutisia friesiana afforded two new 5
      methylcoumaranones, mutisicoumaranones C (3) and D (4). Their structures were
      elucidated by spectroscopic methods. (13)C NMR data for mutisicoumaranones A and
      B are reported for the first time. All compounds showed antifungal activity
      against the phytopathogenic fungus Cladosporium cucumerinum and bactericidal
      activity against Staphylococcus aureus. The presence of 5-methylcoumaranones A-D
      is biosynthetically related to 5-methylcoumarins and phenolic derivatives
      previously isolated from M. friesiana.

PMID- 15165138
TI  - Comparison of fascaplysin and related alkaloids: a study of structures,
      cytotoxicities, and sources.
AB  - The fascaplysin class of compounds have been further investigated from six
      organisms consisting of four sponge collections (Fascaplysinopsis reticulata) and
      two tunicate collections (Didemnum sp.). This work is an extension of an earlier
      communication and reports the isolation of 12 new fascaplysin derivatives: 10
      bromofascaplysin (7), 3,10-dibromofascaplysin (8), homofascaplysate A (9),
      homofascaplysin B-1 (11), 3-bromohomofascaplysins B (12), B-1 (13), and C (15),
      7,14-dibromoreticulatine (17), reticulatol (20), 14-bromoreticulatol (21), and 3
      bromosecofascaplysins A (22) and B (23), along with known compounds: fascaplysin
      (1), reticulatine (4), 3-bromofascaplysin (6), and homofascaplysin C (14).
      Selected compounds were screened in a cell-based cytotoxicity assay with
      compounds 1, 6, and fascaplysin A (24) also screened in the NCI 60 cell line
      panel. A biogenetic pathway for the brominated fascaplysins and brominated
      related alkaloids is proposed and discussed.

PMID- 15165139
TI  - Structure--activity relationships in the fungistatic activity against Botrytis
      cinerea of clovanes modified on ring C.
AB  - The preparation of clovanes 4, 5, 6, 8, and 9, which bear different levels of
      oxidation on ring C, is described for the first time. The biotransformation of
      compounds 5, 6, and 9 by the fungus Botrytis cinerea is investigated, yielding
      compounds 10, 11, and 12, which are described for the first time, together with
      compounds 4-6, 8, and 9. The evaluation of the fungistatic activity against B.
      cinerea of compounds 6, 9, 12, 18, 19, 20, and 21 is reported. Comparison of
      these results with previously published data shows first that the inclusion of
      hydroxyl groups on ring C leads to a decrease in the biological activity and,
      second, that the presence of a 9alpha-hydroxyl group and an alkyl chain at C-2
      plays an important role in the fungistatic activity against B. cinerea of
      compounds with a clovane skeleton.

PMID- 15165140
TI  - Isolation of a library of aromadendranes from Landolphia dulcis and its
      characterization using the VolSurf approach.
AB  - A library of nine aromadendrane-type sesquiterpenes (1-9), including eight new
      natural products (1-5 and 7-9), was isolated from Landolphia dulcis var. barteri
      along with a previously described cadinane derivative (10) and a new muurolane
      derivative (11). The structures of all compounds were established by means of NMR
      methods including COSY, NOESY, HSQC, and HMBC experiments, supported by HRMS and
      optical rotation data. Virtual characterization of the aromadendrane library (1
      9) was performed using chemoinformatics tools. 3D molecular fields were
      calculated with the GRID program using low-energy structures obtained with the
      MMFF force field. VolSurf descriptors were calculated from the GRID maps and
      subsequently analyzed by multivariate statistics. The analysis disclosed the
      presence of a common motif for possible interactions of the aromadendranes with a
      putative target receptor. At the same time, a considerable chemical diversity
      within the library was disclosed, despite a close biosynthetic relationship of
      its members. The results can be interpreted in terms of evolutionary optimization
      of structures of secondary metabolites for interaction with macromolecular
      targets and are of interest in terms of assessment of potential "drug-likeness"
      of natural products.

PMID- 15165141
TI  - Variations in cyclotide expression in viola species.
AB  - Cyclotides, a family of approximately 50 mini-proteins isolated from various
      Violaceae and Rubiaceae plants, are characterized by their circular peptide
      backbone and six conserved cysteine residues arranged in a cystine knot motif.
      Cyclotides show a wide range of biological activities, making them interesting
      targets for both pharmaceutical and agrochemical research, but little is known
      about their natural function and the events that trigger their expression. An
      investigation of the geographical and seasonal variations of cyclotide profiles
      has been performed, using the native Australian violet, Viola hederacea, and the
      Swedish sweet violet, Viola odorata, as model plants. The results showed that in
      the Australian violet the relative peptide levels of some cyclotides remained
      almost constant throughout the year, while other cyclotides were present only at
      certain times of the year. Therefore, it appears that V. hederacea expresses a
      basic armory of cyclotides as well as special "add-ons" whose levels are
      influenced by external factors. In the Swedish violet, cyclotide levels were
      increased up to 14 times during the warmest period of the year. The larger
      variation in expression levels of the Swedish plants may be a reflection of a
      greater climatic variation.

PMID- 15165142
TI  - Tolaasins A--E, five new lipodepsipeptides produced by Pseudomonas tolaasii.
AB  - Pseudomonas tolaasii, the causal organism of brown blotch disease of Agaricus
      bisporus and of the yellowing of Pleurotus ostreatus, was shown to produce in
      culture tolaasin I (1), tolaasin II (2), and five other minor metabolites,
      tolaasins A, B, C, D, and E (3-7). These compounds were demonstrated to be
      important in the development of the disease symptoms. This paper reports on the
      structural elucidation, based essentially on NMR studies and MS spectra, and
      biological activity of the above lipodepsipeptides (3-7). All the above analogues
      showed differences in the peptide moiety, as observed in other lipodepsipeptides
      of bacterial origin, and maintained the beta-hydroxyoctanoyl phi chain at the N
      terminus, except tolaasin A, in which the acyl moiety was a gamma-carboxybutanoyl
      phi moiety. Among the target microorganisms used (fungi, yeast, and bacteria) the
      Gram-positive bacteria were the most sensitive, although the antimicrobial
      activity appeared to be correlated to the structural modification in the
      different analogues. The structure-activity relationships of these toxins are
      discussed.

PMID- 15165143
TI  - New imidazole alkaloids from the Indonesian sponge Leucetta chagosensis.
AB  - Chemical investigation of the sponge Leucetta chagosensis collected in Indonesia
      afforded five new imidazole alkaloids, naamine F (2), naamine G (3), kealiinine A
      (6), kealiinine B (7), and kealiinine C (8), in addition to the known compound
      naamine A (1). Naamine G (3) exhibited strong antifungal activity against the
      phytopathogenic fungus Cladosporium herbarum and also showed mild cytotoxicity
      against mouse lymphoma (L5178Y) and human cervix carcinoma (HeLa) cell lines. In
      the brine shrimp assay, kealiinine A (6) was more active than naamine G (3). The
      structures of the new compounds were unambiguously established by 1D and 2D NMR
      and MS data.

PMID- 15165144
TI  - Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2
      c]pyran-4-one derivatives from the fungus Phellinus igniarius.
AB  - Three unique pyrano[4,3-c][2]benzopyran-1,6-dione derivatives and a new furo[3,2
      c]pyran-4-one, named phelligridins C-F (2-5), together with hispolon (8), (E)-4
      (3,4-dihydroxyphenyl)but-3-en-2-one (9), 4-hydroxybenzaldehyde,
      protocatechualdehyde, syringic acid, protocatechuic acid, caffeic acid,
      isoergosterone, and octadecyl ferulate were isolated and identified from the
      ethanolic extract of Phellinus igniarius. Their structures were determined by
      spectroscopic methods including IR, MS, and 1D and 2D NMR experiments. The
      structures of the new compounds were characterized as 3-(4-hydroxystyryl)-8,9
      dihydroxypyrano[4,3-c]isochromene-4-one (2), 3-(3,4-hydroxystyryl)-8,9
      dihydroxypyrano[4,3-c]isochromene-4-one (3), 8,9-dihydroxy-3-[5',6'-dihydroxy-5'
      '-methyl-3' '-oxo-spiro[fural-2' '(3' 'H),1'-indene]-2'-yl]-1H,6H-pyrano[4,3
      c][2]benzopyran-1,6-dione (4), and (3Z)-3-(3,4-dihydroxybenzylidene)-6-(3,4
      dihydroxystyryl)-2,3-dihydro-2-methoxy-2-(2-oxo-propyl)furo[3,2-c]pyran-4-one
      (5), respectively. Some compounds including 2 and 3 showed in vitro selective
      cytotoxicity against a human lung cancer cell line (A549) and a liver cancer cell
      line (Bel7402). Possible biogenetic sequences to the formation of 1-9 are
      postulated.

PMID- 15165145
TI  - Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)
      dirhamnoside from Bauhinia forficata leaves.
AB  - In vivo and in vitro treatments were carried out to investigate the effects of
      kaempferol-3,7-O-(alpha)-dirhamnoside (kaempferitrin), a major flavonoid compound
      of the n-butanol fraction from Bauhiniaforficata leaves, on serum glucose levels,
      as well as its antioxidant potential. Oral administration of kaempferitrin led to
      a significant hypoglycemic effect in normal and in alloxan-induced diabetic rats.
      In normal rats, blood glucose lowering was observed only with the higher dose of
      kaempferitrin (200 mg/kg) at 1 h after treatment. However, the hypoglycemic
      effect of kaempferitrin in diabetic rats was evident at all doses tested (50,
      100, and 200 mg/kg), and this profile was maintained throughout the period
      studied for both higher doses. Additionally, in glucose-fed hyperglycemic normal
      rats, the kaempferitrin failed to decrease blood glucose levels. In vitro
      antioxidant properties or action against reactive oxygen species of this compound
      was also evaluated. The compound showed high reactivity with 1,1-diphenyl-2
      picryl hydrazyl (DPPH), IC(50) of 84.0 +/- 7.8 microM, inhibited myeloperoxidase
      activity with K(0.5) = 86 +/- 9.9 microM, and decreased lipid peroxidation,
      induced by ascorbyl radical either in microsomes or in asolectin and
      phosphatidylcholine liposomes, with IC(50)'s of 320 +/- 14.1, 223 +/- 8.3, and
      112 +/- 8.8 microM, respectively.

PMID- 15165146
TI  - Terpene isocyanides, isocyanates, and isothiocyanates from the Okinawan marine
      sponge Stylissa sp.
AB  - Seven new nitrogenous terpenoids, (1R,6R,7S,10S)-10-isothiocyanatocadin-4-ene
      (1), (1S,2S,5S,6S,7R,8S)-13-isothiocyanatocubebane (2), (1R,3S,4R,7S,8S,12S,13S)
      7-isocyanoamphilecta-10,14-diene (3), (1S,3S,4R,7S,8S,12S,13S)-8
      isocyanoamphilecta-11(20),14-diene (4), (3S,4R,7S,8S,11S,13S)-8
      isocyanoamphilecta-1(12),14-diene (5), 8-isocyanatocycloamphilect-10-ene (6), and
      8-isothiocyanatocycloamphilect-10-ene (7), were isolated from the Okinawan sponge
      Stylissasp., along with 12 known related compounds. Structural determinations of
      these compounds were made by spectroscopic analysis, and assessment was made of
      their cytotoxicity toward HeLa cells.

PMID- 15165147
TI  - Characterization of an abeo-taxane: brevifoliol and derivatives.
AB  - Brevifoliol is a natural diterpene isolated from Taxus baccata Nutt. A series of
      brevifoliol 1 derivatives, 2-8 and 10, were prepared for characterization and
      semisynthesis purposes and included the introduction of acetyl, Troc, and TES
      groups at C-5 and C-13. Derivatives 16-20 of 5-acetylbrevifoliol 2 were obtained
      via esterification with cinnamic acid, with both 2S-(-)- and 2R-(+)-3
      phenyllactic acid, and with N-benzoyl-(2'R,3'S)-3'-phenylisoserine at C-13.
      Brevifoliol compounds 12, 13, and 15 with either 2S-(-)-phenyllactate moieties at
      C-5 and C-13 or an N-benzoyl-(2'R,3'S)-3'-phenylisoserinyl at C-13 were also
      prepared. An abeo-taxane structure for 1 was clearly defined from the (13)C NMR
      analysis of the 5-acetyl-13-oxo derivative 8 and from the conversion of 1 into
      10, a conformationally restrained compound having a C-13, C-15 oxygen bridge. The
      biological activity of each of these derivatives is being studied.

PMID- 15165148
TI  - Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in
      Scilla peruviana.
AB  - 2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed
      in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2
      dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a
      search for glycosidase inhibitors in this family of plants, we isolated three new
      d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and
      1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position,
      respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful
      inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta
      galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine
      alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3
      hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine
      A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids
      4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of
      6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of
      bacterial beta-glucosidase with an IC(50) value of 5.1 microM.

PMID- 15165149
TI  - Enniatins of Fusarium sp. strain F31 and their inhibition of Botrytis cinerea
      spore germination.
AB  - A spectrum of enniatins was isolated from Fusarium sp. strain F31 by bioassay
      guided isolation directed against Botrytis cinerea. Two new enniatins, J(2) (7)
      and J(3) (8), were co-isolated and both contained, in addition to three
      hydroxyisovaleric acid units, N-methylated l-alanine, l-valine, and l-isoleucine
      units, differing only in their primary sequence. Two other enniatins, named
      enniatin J(1) (1) and enniatin K(1) (6), each containing two N-Me-l-Val units and
      one N-Me-l-Ala or alpha-N-Me-l-butyric acid unit, respectively, were isolated for
      the first time without directed biosynthesis. The enniatin structures were
      elucidated by spectroscopic and chemical methods, and the absolute configuration
      of the amino acids (l) and hydroxyisovaleric acid (d) was consistent with all
      previously isolated enniatins. The known enniatins B (2), B(1) (4), B(2) (5), and
      B(4) (3) were also isolated. The minimum inhibitory concentration of pure
      enniatins against Botrytis cinerea was 75 microg/mL.

PMID- 15165150
TI  - Cytotoxic flavonoids and alpha-pyrones from Cryptocarya obovata.
AB  - One alpha-pyrone, obolactone (1), two chalcones, kurzichalcolactone B (2) and
      obochalcolactone (3), and two flavanones, oboflavanones A (4) and B (5), have
      been isolated from the fruits and the trunk bark of Cryptocarya obovata. The
      structures of the new compounds were elucidated by spectroscopic interpretations.
      The absolute configuration of obolactone (1) was established by circular
      dichroism. Obolactone (1) and obochalcolactone (3) display significant activity
      in in vitro cytotoxic assays against the KB cell line. Biosynthetic pathways for
      oboflavanones and obochalcolactone are suggested.

PMID- 15165151
TI  - New quassinoids, javanicolides C and D and javanicosides B--F, from seeds of
      Brucea javanica.
AB  - Two new quassinoids, javanicolides C and D, and five new quassinoid glucosides,
      javanicosides B-F, were isolated from the seeds of Brucea javanica, along with
      eight known quassinoids, i.e., yadanziolides A, C, D, and S, bruceins D and E,
      brusatol, and the aglycone of yadanzioside D, and 19 known quassinoid glucosides,
      i.e., yadanziosides A-G, I, and K-P, bruceosides A-C and E, and bruceantinoside
      A. Their structures were elucidated by analysis of spectroscopic data and
      chemical evidence.

PMID- 15165152
TI  - Antioxidative constituents from the leaves of Hypericum styphelioides.
AB  - Two new compounds have been isolated from the leaves of Hypericum styphelioides.
      Their structures have been established on the basis of mass spectrometry and 2D
      NMR techniques as 1,3,5-trihydroxy-2-(2',2'-dimethyl-4'
      isopropenyl)cyclopentanylxanthone (1) and 3,5-dihydroxybenzophenon-4-beta-d
      glucoside (2). Known compounds 5-O-demethylpaxanthonin (3) and 3-geranyl-1-(3
      methylbutanoyl)phloroglucinol (4) were also isolated and characterized. Compounds
      1-4 were evaluated for their antioxidative properties in Trolox equivalent
      antioxidant activity (TEAC) and chemiluminescence (CL) assays.

PMID- 15165153
TI  - Isolation, structure, absolute stereochemistry, and HIV-1 integrase inhibitory
      activity of integrasone, a novel fungal polyketide.
AB  - HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition
      is one of the most promising new drug targets for anti-retroviral therapy with
      potentially significant advantages over existing therapies. In this Note, the
      isolation, structure elucidation, and absolute stereochemistry of integrasone, a
      novel polyketide, derived from an unidentified sterile mycelium have been
      described. This bicyclic dihydroxy epoxide lactone inhibited the strand transfer
      reaction of HIV-1 integrase with an IC(50) of 41 microM.

PMID- 15165154
TI  - Ananosic acids B and C, two new 18(13-->12)-abeo-lanostane triterpenoids from
      Kadsura ananosma.
AB  - Two new 18(13-->12)-abeo-lanostane triterpenoid acids, ananosic acids B (1) and C
      (2), were isolated from the stems of Kadsura anaosma. Their structures were
      elucidated by spectral studies and chemical transformation. Compounds 1 and 2
      were evaluated for cytotoxicity using CCRF-CEM leukemia cells and HeLa cells.

PMID- 15165155
TI  - Psychrophilin A and cycloaspeptide D, novel cyclic peptides from the
      psychrotolerant fungus Penicillium ribeum.
AB  - Two fungal metabolites, psychrophilin A (1) and cycloaspeptide D (2), together
      with the known cycloaspeptide A (3) were isolated from the psychrotolerant fungus
      Penicillium ribeum using high-speed countercurrent chromatography (HSCCC) and
      preparative HPLC. The structures were determined from 1D and 2D NMR techniques,
      HREIMS, tandem mass spectrometry (ESMS/MS), and X-ray crystallography. The amino
      acid residues of psychrophilin A (1) and cycloaspeptide D (2) were all found to
      possess the l configuration by Marfey's method. Psychrophilin A (1) is the first
      natural cyclic peptide containing a nitro group instead of an amino group.

PMID- 15165156
TI  - Yucca schidigera bark: phenolic constituents and antioxidant activity.
AB  - Two new phenolic constituents with unusual spirostructures, named yuccaols D (1)
      and E (2), were isolated from the MeOH extract of Yucca schidigera bark. Their
      structures were established by spectroscopic (ESIMS and NMR) analysis. The new
      yuccaols D and E, along with resveratrol (3), trans-3,3',5,5'-tetrahydroxy-4'
      methoxystilbene (4), yuccaols A-C (5-7), yuccaone A (8), larixinol (9), the MeOH
      extract of Yucca schidigera bark, and the phenolic portion of this extract, were
      assayed for antioxidant activity by measuring the free radical scavenging effects
      using two different assays, namely, the Trolox Equivalent Antioxidant Capacity
      (TEAC) assay and the coupled oxidation of beta-carotene and linoleic acid
      (autoxidation assay). The significant activities exhibited by the phenolic
      fraction and its constituents in both tests show the potential use of Y.
      schidigera as a source of antioxidant principles.

PMID- 15165157
TI  - Pentacyclic triterpenoid esters from the fruits of Bruguiera cylindrica.
AB  - Six new pentacyclic triterpenoid esters (1-6) together with 3alpha- and 3beta
      taraxerol were isolated from the fruits of Bruguiera cylindrica. The structures
      of the new compounds were characterized as 3alpha-E-feruloyltaraxerol (1), 3alpha
      Z-feruloyltaraxerol (2), 3beta-E-feruloyltaraxerol (3), 3beta-Z-feruloyltaraxerol
      (4), 3alpha-E-coumaroyltaraxerol (5), and 3alpha-Z-coumaroyltaraxerol (6),
      respectively. Compounds 2 and 6 exhibited weak cytotoxicity against the NCI-H187
      cell line.

PMID- 15165158
TI  - Isotsaokoin, an antifungal agent from Amomum tsao-ko.
AB  - Bioassay-guided purification of a methanol extract from Amomum tsao-ko led to the
      isolation of the bicyclic nonane isotsaokoin (1) as the major active principle,
      an isomer of the previously reported tsaokoin (2). The stereochemical
      relationship of 1 and 2 was investigated by NOE experiments and Mosher ester
      derivatization. Compound 1 showed antifungal activity against Trycophyton
      mentagrophytes.

PMID- 15165159
TI  - New constituents of Artemisia monosperma.
AB  - A new eudesmane sesquiterpene (1) and a C(10) diyne (2) were isolated from the
      aerial parts of Artemisia monosperma. The structures of these compounds were
      determined as rel-1beta,3alpha,6beta-trihydroxyeudesm-4-ene (1) and 1,3R,8R
      trihydroxydec-9-en-4,6-yne (2) on the basis of spectral data interpretation. The
      absolute stereochemistry of 2 was determined using Mosher ester methodology in
      which the terminal primary hydroxyl group was first protected to simplify the
      stereochemical analysis.

PMID- 15165160
TI  - New cytotoxic terpenoids from the wood of Vepris punctata from the Madagascar
      Rainforest.
AB  - Continuation of the chemical examination of the cytotoxic constituents of the
      wood of Vepris punctata resulted in the isolation of the two new terpenoids 1 and
      2 and eight known compounds, glechomanolide (3), isogermafurenolide, (E,E)
      germacra-1(10),4,7(11)-triene, alpha-amyrin, lupeol, lupeyl acetate, taraxerol,
      and 3-epi-taraxerol, in addition to the alkaloids reported reported previously.
      The structures of the two new compounds were established on the basis of 1D and
      2D NMR spectroscopic data interpretation and chemical modifications. All the
      isolated compounds were tested against the A2780 human ovarian cancer cell line;
      the four sequiterpenoids showed moderate cytotoxic activity, while the six
      triterpenoids were inactive.

PMID- 15165161
TI  - A new ursane triterpene from Monochaetum vulcanicum that inhibits DNA polymerase
      beta lyase.
AB  - Bioassay-directed fractionation of a butanone extract of Monochaetum vulcanicum
      resulted in the isolation of a new triterpene (1) and four known compounds,
      ursolic acid (2), 2alpha-hydroxyursolic acid (3), 3-(p-coumaroyl)ursolic acid
      (4), and beta-sitosteryl-beta-d-galactoside (5). The structure of the new
      compound 1 was established as 3beta-acetoxy-2alpha-hydroxyurs-12-en-28-oic acid
      on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical
      derivatization. Compounds 1-3 and 5 exhibited polymerase beta lyase activity.

PMID- 15165162
TI  - Bioactive diterpenoids, a new jatrophane and two ent-abietanes, and other
      constituents from Euphorbia pubescens.
AB  - A new jatrophane diterpene, pubescenol (1), known ent-abietane lactones,
      helioscopinolide A (2) and B (3), and taraxerone, 24-methylenecycloartanol, and
      vanillin have been isolated from Euphorbia pubescens. Diterpenes 1-3 and
      previously described pubescene D (4) were shown to be moderate inhibitors of the
      growth of MCF-7, NCI-H460, and SF-268 human tumor cell lines, whereas compounds 2
      and 3 also exhibited significant antibacterial activity against Staphylococcus
      aureus.

PMID- 15165163
TI  - Three new oxetane-ring-containing taxoids from Taxus chinensis.
AB  - Three new 14beta-benzoyloxy taxoids containing an oxetane ring, namely, 14beta
      benzoyloxybaccatin IV (1), 14beta-benzoyloxy-13-deacetylbaccatin IV (2), and
      14beta-benzoyloxy-2-deacetylbaccatin VI (3), have been isolated from the leaves
      and stems of Taxus chinensis. Their structures were elucidated on the basis of 1D
      and 2D NMR spectroscopic data.

PMID- 15165164
TI  - Further bioactive piperidine alkaloids from the flowers and green fruits of
      Cassia spectabilis.
AB  - The flowers of Cassia spectabilis yielded three new piperidine alkaloids, (-)-3-O
      acetylspectaline (1), (-)-7-hydroxyspectaline (2), and iso-6-spectaline (3),
      together with the known (-)-spectaline (4). The green fruits of this plant were
      also investigated, resulting in the isolation of 1 and 4. Their structures were
      elucidated using a combination of multidimensional NMR and MS techniques, and
      relative stereochemistries were established by NOESY correlations and analysis of
      coupling constants. The DNA-damaging activity of these compounds was evaluated
      using a mutant yeast, Saccharomyces cerevisiae, assay.

PMID- 15165165
TI  - A new 3,4-seco-lupane derivative from Lasianthus gardneri.
AB  - A new seco-ring A lupane triterpene derivative (1), along with lupenone, lupeol,
      beta-sitosterol, ursolic acid, and stigmasterol 3-O-beta-d-glucoside, were
      isolated from a methanol extract of mature stems of Lasianthus gardneri, a shrub
      from the family Rubiaceae growing in Sri Lanka. The structure and stereochemistry
      of the new compound were determined using a combination of (13)C and (1)H homo-
      and heteronuclear 2D NMR experiments and from mass spectral data. The structure
      of 1 was confirmed by partial synthesis from lupeol.

PMID- 15165166
TI  - Three new sesquiterpenes from Croton arboreous.
AB  - Three new sesquiterpenes, 5alpha,7alpha,10betaH-3-patchoulen-2-one (1),
      5alpha,7alpha10betaH-4(14)-patchoulen-2alpha-ol (2), and 9alpha,10beta-dihydroxy
      2beta,4beta-peroxy-1alpha,5beta,7alphaH-guaiane (3), were isolated from the
      aerial parts of Croton arboreous along with 14 known compounds. The structures of
      these compounds were determined on the bases of their spectroscopic data (IR, UV,
      OR, 1D and 2D NMR, and MS). The anti-inflammatory activity against ear edema in
      mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated for all
      the pure compounds and showed that compounds 4-7 are active.

PMID- 15165167
TI  - Eucosterol-type nortriterpenoids from Merwilla natalensis.
AB  - The bulbs of Merwilla natalensis have yielded two known homoisoflavanones, the
      known spirocyclic homoisoflavanone, scillascillin, four known nortriterpenoids,
      and the new nortriterpenoid, (22R,23S)-17alpha,23-epoxy-22,29-dihydroxy-27-nor
      lanost-8-en-3,24-dione (1), bisnortriterpenoid, (22R,23S)-17alpha,23-epoxy
      3beta,22,24xi-trihydroxy-27,28-bisnor-lanost-8-ene (2), and trisnortriterpenoid,
      (23S)-17alpha,23-epoxy-3beta,24xi-dihydroxy-27,28,29-trisnor-lanost-8-ene (3).
      The structures of 1-3 were determined by spectroscopic methods.

PMID- 15165168
TI  - Sesterterpenoids from the marine sponge Hyrtios erectus.
AB  - Four new sesterterpenes, namely, (+)-20-formylhyrtiosal (1), (+)-16-O-acetyl-20
      formylhyrtiosal (2), 12-alpha-O-acetylhyrtiolide (3), and 5,10
      dihydroxyfurospinulosine-1 (4), together with seven known sesterterpenes (5-11)
      were isolated from the marine sponge Hyrtios erectus collected at Hainan, China.
      The structures were elucidated on the basis of extensive spectroscopic analysis
      involving mainly one- and two-dimensional NMR as well as mass spectroscopy.

PMID- 15165169
TI  - The changing face of lab automation.

PMID- 15165171
TI  - Advances in genome biology and technology.

PMID- 15165172
TI  - Integrative approaches in molecular medicine.

PMID- 15165173
TI  - Pharmacogenomic strategies against resistance development in microbial
      infections.
AB  - There are several promising new strategies against resistance development in
      microbial infections. This paper discusses typical experimental and
      bioinformatical strategies to study the impact of infectious challenges on host
      pathogen interaction, followed by several novel approaches and sources for new
      pharmaceutical strategies against resistance development. Genomics reveals
      promising new targets by providing a better understanding of cellular pathways,
      through the identification of new pathways, and by identifying new intervention
      areas, such as phospholipids, glycolipids, innate immunity, and antibiotic
      peptides. Additional antibiotic resources come from new genomes, including marine
      organisms, lytic phages and probiotic strategies. A system perspective regards
      all interactions between the host, pathogen and environment to develop new
      pharmacogenomic strategies against resistance development.

PMID- 15165174
TI  - Impact of proteomics on bladder cancer research.
AB  - Detecting bladder cancer at an early stage and predicting how a tumor will behave
      and act in response to therapy, as well as the identification of new targets for
      therapeutic intervention, are among the main areas of research that will benefit
      from the current explosion in the number of powerful technologies emerging within
      proteomics. The purpose of this article is to briefly review what has been
      achieved to date using proteomic technologies and to bring forward novel
      strategies - based on the analysis of clinically relevant samples - that promise
      to accelerate the translation of basic discoveries into the daily clinical
      practice.

PMID- 15165175
TI  - Genomics and proteomics tools for compound mode-of-action studies in drug
      discovery.
AB  - A broad range of genomics and proteomics technologies are increasingly being
      integrated into emerging research fields such as pharmacogenomics,
      pharmacoproteomics, chemogenomics, chemical genetics, and chemical biology. Here
      we review applications of genomic and proteomic technologies to drug mechanism-of
      action studies and how these are beginning to impact the drug discovery process.

PMID- 15165176
TI  - Automated protein structure homology modeling: a progress report.
AB  - Understanding the molecular function of proteins is greatly enhanced by insights
      gained from their three-dimensional structures. Since experimental structures are
      only available for a small fraction of proteins, computational methods for
      protein structure modeling play an increasingly important role. Comparative
      protein structure modeling is currently the most accurate method, yielding models
      suitable for a wide spectrum of applications, such as structure-guided drug
      development or virtual screening. Stable and reliable automated prediction
      pipelines have been developed to apply large-scale comparative modeling to whole
      genomes or entire sequence databases. Model repositories give access to these
      annotated and evaluated models. In this review, we will discuss recent
      developments in automated comparative modeling and provide selected examples
      illustrating the use of homology models.

PMID- 15165177
TI  - Variation in vaccine response in normal populations.
AB  - Genetic polymorphisms of the human leukocyte antigen (HLA) system significantly
      influence the variation in immune responses to viral vaccines. Considerable data
      on the genetic determinants of immune responses to the measles vaccine support
      the importance of HLA genes in determining the variation in vaccine response. HLA
      class I and class II, TAP, and HLA-DM allele associations with measles-specific
      antibody levels following measles vaccination have revealed, in part, the
      immunologic basis for mechanisms of measles immunity variation. Associations
      between HLA genotype and immune responses have also been reported for other
      vaccines and infectious diseases, such as hepatitis B and C, human
      papillomaviruses, and influenza. Vaccine pharmacogenomics may provide important
      insights for the design and development of new peptide-based vaccines against
      measles and other pathogens.

PMID- 15165178
TI  - How personalized medicine is changing the rules of drug life exclusivity.
AB  - Personalized medicine is premised on the notion that diagnostic techniques can
      improve safety or effectiveness of pharmaceutical therapies based upon individual
      genetic or proteomic make-ups. This article explains how diagnostic techniques
      and pharmaceutical therapies interact during the US Food & Drug Administration's
      approval of branded and generic drugs in the US, and how the same labeling
      requirement for generic drugs of the Hatch-Waxman Act can prevent generic drugs
      from entering the market when proprietary pharmacogenomic techniques are
      incorporated into the labeling of a branded drug.

PMID- 15165179
TI  - Solexa Ltd.
AB  - Solexa Ltd is developing an integrated system, based on a breakthrough single
      molecule sequencing technology, to address a US$2 billion market that is expected
      to grow exponentially alongside and as a consequence of further technological
      enhancements. The system, software and consumables will initially be sold to
      research organizations, pharmaceutical companies and diagnostic companies that
      will sequence large regions of genomic DNA, including whole genomes, at costs
      several orders of magnitude below current levels. Solexa expects to launch its
      first product in 2006, and as it continues to make time and cost efficiencies,
      additional products will be launched into the expanding markets that will have
      broad applications in basic research through to healthcare management.

PMID- 15165180
TI  - VBC-Genomics Bioscience Research GmbH (LLC).
AB  - Founded as a spin-off from the University of Vienna in 1999, VBC-GENOMICS
      Bioscience Research GmbH (LLC) has rapidly gained a strong position within the
      Austrian biotech scene, based on its success as a service provider in
      oligonucleotide synthesis and custom sequencing. In research, the company has
      focused on the development of diagnostic assays based on microarrays. A technical
      platform for amplification and analysis of DNA has been established and validated
      in clinical studies. In addition, the company has developed the world's first
      protein microarray that is certified as an in vitro diagnostic device. This
      microarray contains allergen components and provides a powerful assay for the
      profiling of numerous allergy disease-related antigens. The company also markets
      technological skills and array development expertise to academics and industry.

PMID- 15165181
TI  - Interaction of the plant glycine-rich RNA-binding protein MA16 with a novel
      nucleolar DEAD box RNA helicase protein from Zea mays.
AB  - The maize RNA-binding MA16 protein is a developmentally and environmentally
      regulated nucleolar protein that interacts with RNAs through complex association
      with several proteins. By using yeast two-hybrid screening, we identified a DEAD
      box RNA helicase protein from Zea mays that interacted with MA16, which we named
      Z. maysDEAD box RNA helicase 1 (ZmDRH1). The sequence of ZmDRH1 includes the
      eight RNA helicase motifs and two glycine-rich regions with arginine-glycine-rich
      (RGG) boxes at the amino (N)- and carboxy (C)-termini of the protein. Both MA16
      and ZmDRH1 were located in the nucleus and nucleolus, and analysis of the
      sequence determinants for their cellular localization revealed that the region
      containing the RGG motifs in both proteins was necessary for nuclear/nucleolar
      localization The two domains of MA16, the RNA recognition motif (RRM) and the
      RGG, were tested for molecular interaction with ZmDRH1. MA16 specifically
      interacted with ZmDRH1 through the RRM domain. A number of plant proteins and
      vertebrate p68/p72 RNA helicases showed evolutionary proximity to ZmDRH1. In
      addition, like p68, ZmDRH1 was able to interact with fibrillarin. Our data
      suggest that MA16, fibrillarin, and ZmDRH1 may be part of a ribonucleoprotein
      complex involved in ribosomal RNA (rRNA) metabolism.

PMID- 15165182
TI  - Calmodulin activity and cAMP signalling modulate growth and apical secretion in
      pollen tubes.
AB  - Our present understanding implicates both calmodulin (CaM) and 3',5'-cyclicAMP
      (cAMP) in the regulation of pollen tube growth. However, downstream molecules of
      these signalling pathways and the cellular processes they modulate remain largely
      unknown. In order to elucidate the role of CaM, we mapped its activity in growing
      pollen tubes. 2-chloro-(epsilon-amino-Lys(75))-[6-4-(N,N'-diethylaminophenyl)
      1,3,5-triazin-4-yl]-calmodulin (TA-CaM) and fluorescein-calmodulin (FL-CaM),
      fluorescent analogues of CaM, were loaded into pollen tubes and CaM activity was
      mapped by fluorescence ratio imaging. It was found that CaM activity exhibits a
      tip-focused gradient, similar to the distribution of cytosolic-free calcium
      ([Ca(2+)](c)). In long pollen tubes, apical CaM activity was also found to
      oscillate with a period similar to [Ca(2+)](c) (40-80 sec). This oscillatory
      behaviour was not observed in small pollen tubes or in tubes that had stopped
      growing. Changes in CaM activity within the dome of the pollen tube apex
      resulting from the photolysis of caged photolysis of RS-20 (a peptide antagonist
      of CaM) induced re-orientation of the growth axis, suggesting that CaM is also
      involved in the guidance mechanism. CaM activity was strongly modulated by
      intracellular changes in cAMP (induced by activators and antagonists of adenylyl
      cyclase). These results indicate that the action of this protein is dependent not
      solely on [Ca(2+)](c) but also on a cross-talk with other signalling pathways. A
      putative target of this cross-talk is the secretory machinery as observed in
      pollen tubes loaded with the FM (N-(3-triethylammoniumpropyl)-4-(4
      dibutylamino)styryl)pyridinium dibromide 1-43 dye and exposed to different
      antagonists and activators of these molecules. Our data thus suggest that pollen
      tube growth and orientation depend on an intricate cross-talk between multiple
      signalling pathways in which CaM is a key element.

PMID- 15165183
TI  - Two TIR:NB:LRR genes are required to specify resistance to Peronospora parasitica
      isolate Cala2 in Arabidopsis.
AB  - Resistance responses that plants deploy in defence against pathogens are often
      triggered following a recognition event mediated by resistance (R) genes. The
      encoded R proteins usually contain a nucleotide-binding site (NB) and a leucine
      rich repeat (LRR) domain. They are further classified into those that contain an
      N-terminal coiled coil (CC) motif or a Toll interleukin receptor (TIR) domain.
      Such R genes, when transferred into a susceptible plant of the same or closely
      related species, usually impart full resistance capability. We have used map
      based cloning and mutation analysis to study the recognition of Peronospora
      parasitica (RPP)2 (At) locus in Arabidopsis accession Columbia (Col-0), which is
      a determinant of specific recognition of P. parasitica (At) isolate Cala2.
      Genetic mapping located RPP2 to a 200-kb interval on chromosome 4, which
      contained four adjacent TIR:NB:LRR genes. Mutational analysis revealed three
      classes of genes involved in specifying resistance to Cala2. One class, which
      resulted in pleiotropic effects on resistance to other P. parasitica (At)
      isolates, was unlinked to the RPP2 locus; this class included AtSGT1b. The other
      two classes were mapped within the interval and were specific to Cala2
      resistance. Representatives of each of these classes were sequenced, and
      mutations were found in one or the other of two (RPP2A and RPP2B) of the four
      TIR:NB:LRR genes. RPP2A and RPP2B complemented their specific mutations, but
      failed to impart resistance when present alone, and it is concluded that both
      genes are essential determinants for isolate-specific recognition of Cala2. RPP2A
      has an unusual structure with a short LRR domain at the C-terminus, preceded by
      two potential but incomplete TIR:NB domains. In addition, the RPP2A LRR domain
      lacks conserved motifs found in all but three other TIR:NB:LRR class proteins. In
      contrast, RPP2B has a complete TIR:NB:LRR structure. It is concluded that RPP2A
      and RPP2B cooperate to specify Cala2 resistance by providing recognition or
      signalling functions lacked by either partner protein.

PMID- 15165184
TI  - Senescence-induced expression of cytokinin reverses pistil abortion during maize
      flower development.
AB  - Maize is a monoecious species that produces imperfect (unisexual), highly derived
      flowers called florets. Within the spikelet, the basic repeating unit of the
      maize inflorescence, the spikelet meristem gives rise to an upper and a lower
      floret. Although initially bisexual, floret unisexuality is established through
      selective organ elimination. In addition, the lower floret of each ear spikelet
      is aborted early in its development, leaving the upper floret to mature as the
      only pistillate floret. Expression from the cytokinin-synthesizing isopentenyl
      transferase (IPT) enzyme under the control of the Arabidopsis senescence
      inducible promoter SAG (senescence associated gene)12 was observed during early
      maize floret development. Moreover, the lower floret was rescued from abortion,
      resulting in two functional florets per spikelet. The pistil in each floret was
      fertile, but the spikelet produced just one kernel composed of a fused endosperm
      with two viable embryos. The two embryos were genetically distinct, indicating
      that they had arisen from independent fertilization events. These results suggest
      that cytokinin can determine pistil cell fate during maize floret development.

PMID- 15165185
TI  - The Etched1 gene of Zea mays (L.) encodes a zinc ribbon protein that belongs to
      the transcriptionally active chromosome (TAC) of plastids and is similar to the
      transcription factor TFIIS.
AB  - Etched1 (et1) is a pleiotropic, recessive mutation of maize that causes fissured
      and cracked mature kernels and virescent seedlings. Microscopic examinations of
      the et1 phenotype revealed an aberrant plastid development in mutant kernels and
      mutant leaves. Here, we report on the cloning of the et1 gene by transposon
      tagging, the localization of the gene product in chloroplasts, and its putative
      function in the plastid transcriptional apparatus. Several alleles of Mutator
      (Mu)-induced et1 mutants, the et1-reference (et1-R) mutant, and Et1 wild-type
      were cloned and analyzed at the molecular level. Northern analyses with wild-type
      plants revealed that Et1 transcripts are present in kernels, leaves, and other
      types of tissue, and no Et1 expression could be detected in the et1 mutants
      analyzed. The ET1 protein is imported by chloroplasts and has been
      immunologically detected in transcriptionally active chromosome (TAC) fractions
      derived from chloroplasts. Accordingly, the relative transcriptional activity of
      TAC fractions was significantly reduced in chloroplasts of et1-R plants. ET1 is
      the first zinc ribbon (ZR) protein shown to be targeted to plastids. With regard
      to its localization and its striking structural similarity to the eukaryotic
      transcription elongation factor TFIIS, it is feasible that ET1 functions in
      plastid transcription elongation by reactivation of arrested RNA polymerases.

PMID- 15165186
TI  - Arabidopsis thaliana plants overexpressing thylakoidal ascorbate peroxidase show
      increased resistance to Paraquat-induced photooxidative stress and to nitric
      oxide-induced cell death.
AB  - Ascorbate peroxidases (APX), localized in the cytosol, peroxisomes, mitochondria
      and chloroplasts of plant cells, catalyze the reduction of H(2)O(2) to water by
      using ascorbic acid (ASA) as specific electron donor. The chloroplastic
      isoenzymes of APX are involved in the water-water cycle, which contributes to the
      photophosphorylation coupled to the photosynthetic electron transport. In order
      to better clarify the contribution of thylakoidal APX (tAPX) to the reactive
      oxygen species (ROS) scavenging activity, as well as to the fine modulation of
      ROS for signaling, we produced Arabidopsis lines overexpressing tAPX. These lines
      show an increased resistance to treatment with the O(2)(-) generating herbicide
      Paraquat (Pq). However, when challenged with photoinhibitory treatments at high
      light or low temperature, or with iron (Fe) or copper (Cu) overload, the tAPX
      overexpressing lines show no increased resistance with respect to controls,
      indicating that in such experimental conditions, tAPX overexpression does not
      reinforce plant defenses against the oxidative stresses tested. Interestingly,
      the nitric oxide (NO)-donor sodium nitroprusside (SNP) represses accumulation of
      tAPX transcript; SNP also partially inhibits tAPX enzymatic activity. After
      treatment with SNP, the tAPX-overexpressing lines show reduced symptoms of damage
      with respect to control plants treated with SNP. These transgenic lines confirm
      that H(2)O(2) acts in partnership with NO in causing cell death and highlight the
      important role of tAPX in the fine modulation of H(2)O(2) for signaling.

PMID- 15165187
TI  - The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage
      repair and homologous recombination.
AB  - Rad17 is involved in DNA checkpoint control in yeast and human cells. A homologue
      of this gene as well as other genes of the pathway (the 9-1-1 complex) are
      present in Arabidopsis and share conserved sequence domains with their yeast and
      human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17
      mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and
      mitomycin C (MMC), which can be reversed by complementation, suggesting that the
      loss of function of Rad17 disturbs DNA repair in plant cells. Our results are
      further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which
      is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic
      as the double mutant is not more sensitive to the chemicals than the single
      mutants. The mutants show a delay in the general repair of double-strand breaks
      (DSBs). However, frequencies of intrachromosomal homologous recombination (HR)
      are enhanced. Nevertheless, the mutants are proficient for a further induction of
      HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is
      associated with a general deregulation of DNA repair, which seems to be
      correlated with a deficiency in non-homologous DSB repair.

PMID- 15165188
TI  - Phytocalpain controls the proliferation and differentiation fates of cells in
      plant organ development.
AB  - Calpain, a calcium-dependent cysteine protease, plays an essential role in basic
      cellular processes in animal cells, including cell proliferation, apoptosis, and
      differentiation. NbDEK encodes the calpain homolog of N. benthamiana. In this
      study, virus-induced gene silencing (VIGS) of NbDEK resulted in arrested organ
      development and hyperplasia in all the major plant organs examined. The epidermal
      layers of the leaves and stems were covered with hyperproliferating cell masses,
      and stomata and trichome development was severely inhibited. During flower
      development, a single dome-like structure was grown from the flower meristem to
      generate a large cylinder-shaped flower lacking any floral organs. At the
      cellular level, cell division was sustained in tissues that were otherwise
      already differentiated, and cell differentiation was severely hampered. NbDEK is
      ubiquitously expressed in all the plant tissues examined. In the abnormal organs
      of the NbDEK VIGS lines, protein levels of D-type cyclins (CycD)2, CycD3, and
      proliferating cell nuclear antigen (PCNA) were greatly elevated, and
      transcription of E2F (E2 promoter binding factor), E2F-regulated genes,
      retinoblastoma (Rb), and KNOTTED1 (KN1)-type homeobox genes was also stimulated.
      These results suggest that phytocalpain is a key regulator of cell proliferation
      and differentiation during plant organogenesis, and that it acts partly by
      controlling the CycD/Rb pathway.

PMID- 15165189
TI  - Identification of cold-inducible downstream genes of the Arabidopsis DREB1A/CBF3
      transcriptional factor using two microarray systems.
AB  - The transcriptional factor DREB/CBF (dehydration-responsive element/C-repeat
      binding) specifically interacts with the dehydration-responsive element (DRE)/C
      repeat (CRT) cis-acting element (A/GCCGAC) and controls the expression of many
      stress-inducible genes in Arabidopsis. Transgenic plants overexpressing DREB1A
      showed activated expression of many stress-inducible genes and improved tolerance
      to not only drought, salinity, and freezing but also growth retardation. We
      searched for downstream genes in transgenic plants overexpressing DREB1A using
      the full-length cDNA microarray and Affymetrix GeneChip array. We confirmed
      candidate genes selected by array analyses using RNA gel blot and identified 38
      genes as the DREB1A downstream genes, including 20 unreported new downstream
      genes. Many of the products of these genes were proteins known to function
      against stress and were probably responsible for the stress tolerance of the
      transgenic plants. The downstream genes also included genes for protein factors
      involved in further regulation of signal transduction and gene expression in
      response to stress. The identified genes were classified into direct downstream
      genes of DREB1A and the others based on their expression patterns in response to
      cold stress. We also searched for conserved sequences in the promoter regions of
      the direct downstream genes and found A/GCCGACNT in their promoter regions from 
      51 to -450 as a consensus DRE. The recombinant DREB1A protein bound to A/GCCGACNT
      more efficiently than to A/GCCGACNA/G/C.

PMID- 15165190
TI  - Identification and characterization of a novel anthocyanin malonyltransferase
      from scarlet sage (Salvia splendens) flowers: an enzyme that is phylogenetically
      separated from other anthocyanin acyltransferases.
AB  - Anthocyanin acyltransferases (AATs) catalyze a regiospecific acyl transfer from
      acyl-CoA to the glycosyl moiety of anthocyanins, thus playing an important role
      in flower coloration. The known AATs are subfamily members of an acyltransferase
      family, the BAHD family, which play important roles in secondary metabolism in
      plants. Here, we describe the purification, characterization, and cDNA cloning of
      a novel anthocyanin malonyltransferase from scarlet sage (Salvia splendens)
      flowers. The purified enzyme (hereafter referred to as Ss5MaT2) is a monomeric 46
      kDa protein that catalyzes the transfer of the malonyl group from malonyl-CoA to
      the 4"'-hydroxyl group of the 5-glucosyl moiety of anthocyanins. Thus, it is a
      malonyl-CoA:anthocyanin 5-glucoside 4"'-O-malonyltransferase. On the basis of the
      partial amino acid sequences of the purified enzyme, we isolated a cDNA that
      encodes an acyltransferase protein. The steady-state transcript level of the gene
      was the highest in recently opened, fully pigmented flowers and was also
      correlated with the trend observed for an AAT gene responsible for the first
      malonylation step during salvianin biosynthesis. Immunoprecipitation studies
      using antibodies against the recombinant acyltransferase protein corroborated the
      identity of this cDNA as that encoding Ss5MaT2. The deduced amino acid sequence
      of Ss5MaT2 showed a low similarity (22-24% identity) to those of AATs and lacked
      the AAT-specific signature sequence. A phylogenetic analysis suggested that
      Ss5MaT2 is more related to acetyl-CoA:benzylalcohol acetyltransferase (BEAT)
      rather than to AAT. This is another example in which enzymes with similar,
      although not identical, substrate evolved from different branches of the BAHD
      family.

PMID- 15165191
TI  - Geminivirus VIGS of endogenous genes requires SGS2/SDE1 and SGS3 and defines a
      new branch in the genetic pathway for silencing in plants.
AB  - Virus-induced gene silencing (VIGS) is a sequence-specific RNA degradation
      process that can be used to downregulate plant gene expression. Both RNA and DNA
      viruses have been used for VIGS, but they differ in their mode of replication,
      gene expression, and cellular location. This study examined silencing mediated by
      a DNA virus, cabbage leaf curl virus (CaLCuV), in several silencing-deficient
      Arabidopsis mutants. A DNA VIGS vector derived from CaLCuV, which silenced
      chlorata42 (ChlI) needed for chlorophyll formation, was used to test endogenous
      gene silencing responses in suppressor of gene silencing (sgs)1, sgs2, sgs3, and
      Argonaute (ago)1 mutants defective in sense transgene-mediated post
      transcriptional silencing (S-PTGS). SGS2/silencing defective (SDE)1, SGS3, and
      AGO1 are each dispensable for silencing mediated by transgenes containing
      inverted repeats (IR-PTGS), and SGS2/SDE1 is dispensable for RNA VIGS. We show
      that DNA VIGS requires both SGS2/SDE1 and SGS3, regardless of the orientation of
      362 nt ChlI transcripts produced from the viral DNA promoter. Viral DNA
      accumulation is slightly higher, and viral symptoms increase in sgs2 and sgs3,
      whereas overexpression of SGS2/SDE1 mRNA results in decreased viral symptoms.
      Mutants affected in SGS1 and AGO1 function are only delayed in the onset of
      silencing, and have a small effect on chlorophyll accumulation. DNA VIGS is
      unaffected in defective DNA methylation (ddm)1/somniferous (som)8 and maintenance
      of methylation (mom)1 mutants, impaired for TGS. These results demonstrate that
      SGS2/SDE1 and SGS3 are needed for endogenous gene silencing from DNA viruses, and
      suggest that SGS2/SDE1 may reduce geminivirus symptoms by targeting viral mRNAs.

PMID- 15165192
TI  - Non-invasive online detection of nitric oxide from plants and some other
      organisms by mass spectrometry.
AB  - As nitric oxide (NO) is a key messenger in many organisms, reliable techniques
      for the detection of NO are essential. Here, it is shown that a combination of
      membrane inlet mass spectrometry (MIMS) and restriction capillary inlet mass
      spectrometry (RIMS) allows for the fast, specific, and non-invasive online
      detection of NO that has been emitted from tissue cultures of diverse organisms,
      or from whole plants. As an advantage over other NO assays, MIMS/RIMS
      discriminates nitrogen isotopes and simultaneously measures NO and O(2) (and
      other gases) from the same sample. MIMS/RIMS technology may thus help to identify
      the source of gaseous NO in cells, and elucidate the relationship between primary
      gas metabolism and NO formation. Using RIMS, it is demonstrated that the novel
      fungicide F 500((R)) triggers NO production in plants.

PMID- 15165194
TI  - The preauricular sinus: a review of its clinical presentation, treatment, and
      associations.
AB  - Preauricular sinuses (ear pits) are common congenital abnormalities. Usually
      asymptomatic, they manifest as small dells adjacent to the external ear near the
      anterior margin of the ascending limb of the helix, most frequently on the right
      side. Preauricular sinuses can be either inherited or sporadic. When inherited,
      they show an incomplete autosomal dominant pattern with reduced penetrance and
      variable expression. They may be bilateral, increasing the likelihood of being
      inherited, in 25-50% of cases. Preauricular sinuses are features of other
      conditions or syndromes in 3-10% of cases, primarily in association with deafness
      and branchio-oto-renal (BOR) syndrome. When other congenital anomalies coexist
      with these sinuses, auditory testing and renal ultrasound should be considered.
      Sinuses may become infected, most commonly with gram-positive bacteria, in which
      case their exudates should be cultured and appropriate antibiotics administered.
      Recurrent infection is a clear indication for complete excision and provides the
      only definitive cure. Recurrence rates after surgery range from 9% to 42%.
      Meticulous excision by an experienced head and neck surgeon minimizes the risk of
      recurrence.

PMID- 15165195
TI  - Lichen striatus: clinical and laboratory features of 115 children.
AB  - To analyze the clinical features, response to treatment, and follow-up of lichen
      striatus and any associated symptoms or disease, we designed a retrospective
      study involving 115 affected children at the Pediatric Dermatology Unit of the
      Department of Dermatology of the University of Bologna, Bologna, Italy. Between
      January 1989 and January 2000 we diagnosed lichen striatus in 37 boys and 78
      girls (mean age 4 years 5 months). We studied their family history and the season
      of onset, morphology, distribution, extent, duration, histopathology, and
      treatment of their lichen striatus. We found that family history was negative in
      all our patients except for two pairs of siblings. The majority of children had
      the disease in the cold seasons; precipitating factors were found in only five
      cases. The most frequently involved sites were the limbs, with no substantial
      difference between upper and lower limb involvement. When lichen striatus was
      located on the trunk and face, it always followed Blaschko lines; in seven
      children the bands on the limbs appeared to be along the axial lines of
      Sherrington. In 70 cases, lichen striatus was associated with atopy. The mean
      duration of the disease was 6 months and relapses were observed in five children,
      and in one instance the disease had a prolonged course. Only a few case study
      series of lichen striatus in children have been reported and ours is the largest
      to date. The etiology of lichen striatus remains unknown in the majority of our
      patients. The confirmed association with atopy observed in our patients may be a
      predisposing factor. It has generally been accepted that lichen striatus follows
      the lines of Blaschko, and this distribution is a sign of both a topographic and
      a pathogenetic concept. In patients where lichen striatus is along axial lines, a
      locus minoris resistentiae, we suppose that this distribution may only be an
      illusory phenomenon in instances in which the trigger factor prefers this route,
      consisting of several successive Blaschko lines, but appearing as a single band.

PMID- 15165196
TI  - Dermatitis artefacta in pediatric patients: experience at the national institute
      of pediatrics.
AB  - Dermatitis artefacta is a factitious disorder in which there is deliberate
      conscious production of skin lesions. There are only a few reports that evaluate
      instances of dermatitis artefacta in the pediatric population. The aim of this
      retrospective study was to assess the characteristics of patients with this
      disorder who were seen at the National Institute of Pediatrics in Mexico City.
      The records of all patients diagnosed with dermatitis artefacta from January 1980
      to December 1999 were analyzed. There were 29 patients (25 females, 4 males). The
      upper limbs and the face were the most commonly involved areas. Superficial
      erosions were the most frequent initial event, and residual lesions consisted of
      scars and crusts. Time taken to diagnosis was on average 10 months. Half of the
      patients were lost to follow-up. No correlation was found between the length of
      time from the disease onset to diagnosis, the type of lesions, and the clinical
      outcome. Twelve patients had an associated systemic disorder. The possible
      association with chronic disease has not been sufficiently stressed and
      demonstrates the importance of providing psychological support for these
      patients. Psychiatric diagnoses were anxiety, depression, and personality
      disorder. No correlation was found between the psychiatric diagnosis and the
      outcome of dermatitis artefacta. A young age at presentation, which has been
      considered important as a favorable prognostic sign, could not be demonstrated in
      our patients.

PMID- 15165197
TI  - Three children with CD30 cutaneous anaplastic large cell lymphomas bearing the
      t(2;5)(p23;q35) translocation.
AB  - Since its discovery in CD30(+) anaplastic large cell lymphomas, the
      t(2;5)(p23;q35) translocation has shown a high degree of association with nodal
      disease, younger patient age, and better prognosis. Furthermore, primary
      cutaneous CD30(+) anaplastic large cell lymphomas rarely manifests the t(2;5)
      translocation. We present three cases of this disease that occurred in children,
      bore the t(2;5) translocation, and had excellent outcomes, but presented
      cutaneously. Two of these lesions were primary skin lymphomas. Review of the
      available literature in conjunction with these three cases suggests that the
      t(2;5) translocation may be more strongly associated with younger patient age and
      favorable outcomes rather than nodal versus cutaneous site of presentation.

PMID- 15165198
TI  - Frequency and clinical and dermatoscopic features of volar and ungual pigmented
      melanocytic lesions: a study in schoolchildren of Manizales, Colombia.
AB  - In Latin American populations, acral lentiginous melanoma is the prevailing type
      of melanoma. Its relationship to preexistent benign volar melanocytic lesions has
      not been established; however, it is common practice to remove these lesions from
      children in spite of the fact that childhood acral lentiginous melanoma is
      extremely rare. To determine the frequency and the clinical and dermatoscopic
      characteristics of acrally located pigmented melanocytic lesions in
      schoolchildren of Manizales, Colombia, we undertook an exploratory, descriptive
      study of 1106 schoolchildren in search of pigmented volar and ungual lesions. In
      the study group there were 680 males and 426 females, ranging in age from 6 to 23
      years (median age 13 years). At least one acral pigmented lesion was found in 464
      individuals (42%). Their distribution over the volar surface was rather regular.
      Increasing age and darkness of the skin correlated with an increased number of
      lesions. Dermatoscopic patterns were consistent and suggestive of union nevus and
      simple lentigo as the predominant types of melanocytic proliferation. Typical
      pigmented melanocytic volar skin lesions are very common in our schoolchildren.
      Removal of these lesions is not routinely recommended since a relationship with
      acral lentiginous melanoma has not been established.

PMID- 15165199
TI  - Periumbilical allergic contact dermatitis: blue jeans or belt buckles?
AB  - Nickel is the most ubiquitous contact allergen among children and adolescents.
      Metal blue jeans buttons and belts have been noted to cause nickel dermatitis
      around the umbilicus. For these children, traditional teaching is strict
      avoidance of all pants with metal snaps/buttons, particularly blue jeans. In this
      study we tested 90 pairs of blue jeans and 47 belts for nickel using the
      dimethylglyoxime spot test. Only 10% of blue jeans tested positive, while 53% of
      belts tested positive. Furthermore, 10 pairs of nickel-negative blue jeans
      remained negative after 10 washings. Overall we found no resistance to testing in
      clothing stores. From these results, we recommend that patients with allergic
      contact dermatitis secondary to nickel need not strictly avoid blue jeans and
      metal belt buckles. Rather, families should be encouraged to use the
      dimethylglyoxime spot test to test these items for nickel prior to purchase.

PMID- 15165200
TI  - Erythema nodosum in association with celiac disease.
AB  - We present a 16-year-old girl with a 4-year history of chronic persistent
      erythema nodosum. Recurrently low serum iron values suggested the possibility of
      a malabsorption syndrome. The presence of antitransglutaminase and antiendomysium
      antibodies and the jejunal biopsy specimen findings showed an underlying celiac
      disease. On a strict gluten-free diet, the skin lesions resolved and the girl has
      since remained symptom free for 9 months. Thus celiac disease can be a triggering
      factor for erythema nodosum. In the chronic form of the skin lesions, serologic
      testing for this specific enteropathy may be justified.

PMID- 15165201
TI  - Dermatologic signs of biotin deficiency leading to the diagnosis of multiple
      carboxylase deficiency.
AB  - The biotin-responsive, multiple carboxylase deficiencies are autosomal
      recessively inherited disorders of metabolism in which biotin-dependent
      carboxylases show diminished activity. This results in an accumulation of organic
      acids in the urine. The clinical picture involves the nervous system, skin,
      respiratory system, digestive system, and immune system. The disorder has a good
      prognosis if biotin therapy is introduced early. If not, it can result in
      irreversible damage to the central nervous system and early death from metabolic
      acidosis. We report a 4-year-old girl with unexplained seizures that did not
      respond well to anticonvulsants. The development of skin problems, which
      histologically could match the diagnosis of a nutritional dermatitis, together
      with the fact that the child was constantly eating without gaining weight, led us
      to the diagnosis of a metabolic disorder. The accumulation of organic acids in
      the urine suggested the possibility of a biotin deficiency. With biotin therapy
      the skin problems resolved completely. The seizures also diminished. This case
      shows that in young children with unexplained seizures that do not respond well
      to classic anticonvulsant therapy, the possibility of biotin deficiency should
      always be considered. This article also includes a thorough review of the skin
      manifestations and other problems caused by biotin deficiency.

PMID- 15165202
TI  - Acetaminophen-induced toxic epidermal necrolysis in a child.
AB  - Toxic epidermal necrolysis (TEN) is a severe, life-threatening disorder that
      usually affects adults. It is often drug induced. We report an instance of a
      severe case of TEN in a 6-year-old boy, probably induced by acetaminophen, and
      less likely by codeine. A lymphocyte stimulation test could not identify the
      culprit drug. Treatment with intravenous immunoglobulin seemed to halt the
      disease progression.

PMID- 15165203
TI  - An unusual case of factitious onychodystrophy.
AB  - Nail disorders are a common dermatologic problem, and when such disorders are
      self-induced, the diagnosis and treatment can be challenging. We present an
      unusual instance of factitious onychodystrophy with associated erythronychia of
      the nail bed.

PMID- 15165204
TI  - The importance of screening for sight-threatening retinopathy in incontinentia
      pigmenti.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant disorder of ectodermal
      structures affecting the skin, hair, teeth, eyes, and central nervous system. The
      four classic cutaneous stages of the disorder are well known to pediatric
      dermatologists. However, ocular and neurologic sequelae represent the major
      morbidity in IP. The two patients reported here highlight some of the potential
      ocular manifestations of IP and emphasize the importance of early ophthalmologic
      assessment in this condition.

PMID- 15165205
TI  - Fatal cytophagic histiocytic panniculitis.
AB  - Individual cases of so-called Weber-Christian disease with a bleeding diathesis
      have been reported for several years. These were originally diagnosed as Weber
      Christian disease, but have been recategorized on review as a chronic, visceral,
      and cutaneous histiocytic (cytophagic) panniculitis, progressing to liver
      dysfunction and jaundice and a terminal hemorrhagic diathesis. We report here a
      rare catastrophic form of systemic panniculitis in an adolescent girl. Despite
      compelling clinical evidence, the diagnosis was made only on postmortem biopsies.

PMID- 15165206
TI  - Baboon syndrome in childhood: easy to avoid, easy to diagnose, but the problem
      continues.
AB  - Baboon syndrome was first described as a particular type of systemic contact
      dermatitis, characterized by an exanthem with involvement of the buttocks and
      flexures. In children, it is an important entity to take into account for the
      differential diagnosis of viral exanthem. A large number of allergens have been
      implicated, although inhalation of mercury vapor is a common trigger. We present
      the findings in 14 patients younger than 14 years with baboon syndrome. We also
      look at the frequency in children and the most common causes and triggers in our
      area.

PMID- 15165208
TI  - Invasive fungal dermatitis in a 770 gram neonate.
AB  - A 770 g birthweight, 25-weeks gestation infant girl was born from a bigeminal
      pregnancy. Six days later she developed erythematous "diaper dermatitis" and
      maceration of the flexural areas. Despite topical antifungal therapy,
      erythematous plaques appeared 2 days later on the back. Within less than 24
      hours, skin erosions with crusting appeared and spread over the whole body.
      Candida albicans was found in cutaneous scales, and blood, umbilical catheter,
      and cerebrospinal fluid cultures. In spite of intravenous fluconazole therapy,
      her general condition deteriorated and she died 2 days later. This premature
      neonate had a typical case of invasive fungal dermatitis, which is characterized
      by diffuse erosive and crusting cutaneous lesions appearing several days after
      birth and a high rate of systemic fungal infection (mainly but not exclusively)
      due to Candida sp. Mortality is high and prompt diagnosis and initiation of
      antifungal therapy appears to be the most important factor for survival.

PMID- 15165209
TI  - Flushing due to solitary cutaneous mastocytoma can be prevented by hydrocolloid
      dressings.
AB  - Solitary mastocytomas occur commonly and can occasionally be associated with
      troublesome flushing related to rubbing. We report a child with a solitary
      mastocytoma who repeatedly and reproducibly caused flushing only with rubbing and
      scratching. Conventional treatment with antihistamines was not completely
      effective and caused sedation. A trial application of double-layer hydrocolloid
      dressing led to complete abolition of flushing episodes until the child reached
      an age where he could peel off the dressings. This treatment is particularly
      suited to very young children with solitary mastocytomas whose parents do not
      feel comfortable with antihistamine treatment, topical or intralesional
      corticosteroids, or surgical interventions. This treatment may be used alone or
      in conjunction with conventional therapy where there has been a failure to
      achieve complete control of flushing and/or blistering.

PMID- 15165207
TI  - Mercury intoxication: it still exists.
AB  - A3-year-old boy presented to the Hospital for Sick Children with systemic
      symptoms and oropharyngeal and peripheral extremity changes suggestive of
      Kawasaki disease. He was found to have severe hypertension. Investigation for a
      catecholamine-secreting tumor was negative. Toxins were considered when the
      patient's 20-month-old brother presented with similar symptoms, and the boys were
      subsequently diagnosed with elemental mercury poisoning. We review the literature
      on mercury intoxication and discuss the historical context, clinical syndrome
      (acrodynia), treatment, and radiologic findings of this unusual diagnosis.

PMID- 15165210
TI  - What syndrome is this? Acquired progressive kinking of the hair.

PMID- 15165211
TI  - Multiple milia-like dermal papules.

PMID- 15165212
TI  - Dermatitis artefacta.

PMID- 15165215
TI  - Extensive pityriasis alba in a child with atopic dermatitis.

PMID- 15165216
TI  - Idiopathic pyoderma gangrenosum in a child.

PMID- 15165217
TI  - Generalized acanthosis nigricans in childhood.

PMID- 15165218
TI  - Childhood herpes zoster complicated by neurogenic bladder dysfunction.

PMID- 15165219
TI  - Dexamethasone pulse therapy for scleredema.

PMID- 15165220
TI  - Bullous necrotizing fixed drug eruption in an infant.

PMID- 15165222
TI  - Methotrexate in severe childhood psoriasis.

PMID- 15165221
TI  - Recurrent Stevens-Johnson syndrome in winter.

PMID- 15165223
TI  - Literature review.

PMID- 15165227
TI  - New targets of the PII signal transduction protein identified in cyanobacteria.

PMID- 15165228
TI  - Structure, function and evolution of microbial adenylyl and guanylyl cyclases.
AB  - Cells respond to signals of both environmental and biological origin. Responses
      are often receptor mediated and result in the synthesis of so-called second
      messengers that then provide a link between extracellular signals and downstream
      events, including changes in gene expression. Cyclic nucleotides (cAMP and cGMP)
      are among the most widely studied of this class of molecule. Research on their
      function and mode of action has been a paradigm for signal transduction systems
      and has shaped our understanding of this important area of biology. Cyclic
      nucleotides have diverse regulatory roles in both unicellular and multicellular
      organisms, highlighting the utility and success of this system of molecular
      communication. This review will examine the structural diversity of microbial
      adenylyl and guanylyl cyclases, the enzymes that synthesize cAMP and cGMP
      respectively. We will address the relationship of structure to biological
      function and speculate on the complex origin of these crucial regulatory
      molecules. A review is timely because the explosion of data from the various
      genome projects is providing new and exciting insights into protein function and
      evolution.

PMID- 15165229
TI  - Encoded errors: mutations and rearrangements mediated by misalignment at
      repetitive DNA sequences.
AB  - Mutations and rearrangements that occur by misalignment during DNA replication
      are frequent sources of genetic variation in bacteria. Dislocations between a
      replicating strand and its template at repetitive DNA sequences underlie the
      mechanism of these genetic events. Such misalignments can be transient or stable
      and can involve intramolecular or intermolecular DNA mispairing, even pairing
      across a replication fork. Paradoxically, these replication 'slippage' events
      both create and destroy repetitive sequences in bacterial genomes. This review
      catalogues several types of slippage errors, presents the cellular processes that
      act to limit them and discusses the consequences of this class of genetic events
      on the evolution of bacterial genomes and physiology.

PMID- 15165231
TI  - Identification of novel dominant INO2c mutants with an Opi- phenotype.
AB  - The INO2 gene of Saccharomyces cerevisiae is required for derepression of the
      phospholipid biosynthetic genes in response to inositol depletion. Conversely,
      the OPI1 gene is required for repression in response to inositol supplementation.
      Results of an in vitro assay have led to a model in which Opi1p interacts with
      Ino2p. However, there is no in vivo evidence to support this model. Additionally,
      most of the previously isolated ino2 mutants offer little insight into this
      model. Here, we report the isolation of a new class of dominant mutations in the
      INO2 gene, which yield constitutive expression of a target gene (i.e. an Opi(-)
      mutant phenotype). Two mutations reside in a region of the Ino2p required for
      interaction with Opi1p in vitro. Three other mutations are at the amino-terminus
      in a transcriptional activation domain.

PMID- 15165230
TI  - Screening for synthetic lethal mutants in Escherichia coli and identification of
      EnvC (YibP) as a periplasmic septal ring factor with murein hydrolase activity.
AB  - Bacterial cytokinesis is driven by the septal ring apparatus, the assembly of
      which in Escherichia coli is directed to mid-cell by the Min system. Despite
      suffering aberrant divisions at the poles, cells lacking the minCDE operon (Min(
      )) have an almost normal growth rate. We developed a generally applicable
      screening method for synthetic lethality in E. coli, and used it to select for
      transposon mutations (slm) that are synthetically lethal (or sick) in combination
      with DeltaminCDE. One of the slm insertions mapped to envC (yibP), proposed to
      encode a lysostaphin-like, metallo-endopeptidase that is exported to the
      periplasm by the general secretory (Sec) pathway. Min(-) EnvC(-) cells showed a
      severe division defect, supporting a role for EnvC in septal ring function.
      Accordingly, we show that an EnvC-green fluorescent protein fusion, when directed
      to the periplasm via the twin-arginine export system, is both functional and part
      of the septal ring apparatus. Using an in-gel assay, we also present evidence
      that EnvC possesses murein hydrolytic activity. Our results suggest that EnvC
      plays a direct role in septal murein cleavage to allow outer membrane
      constriction and daughter cell separation. By uncovering genetic interactions,
      the synthetic lethal screen described here provides an attractive new tool for
      studying gene function in E. coli.

PMID- 15165232
TI  - Oligomeric structure of the Bacillus subtilis cell division protein DivIVA
      determined by transmission electron microscopy.
AB  - DivIVA from Bacillus subtilis is a bifunctional protein with distinct roles in
      cell division and sporulation. During vegetative growth, DivIVA regulates the
      activity of the MinCD complex, thus helping to direct cell division to the
      correct mid-cell position. DivIVA fulfils a quite different role during
      sporulation in B. subtilis when it directs the oriC region of the chromosome to
      the cell pole before asymmetric cell division. DivIVA is a 19.5 kDa protein with
      a large part of its structure predicted to form a tropomyosin-like alpha-helical
      coiled-coil. Here, we present a model for the quaternary structure of DivIVA,
      based on cryonegative stain transmission electron microscopy images. The purified
      protein appears as an elongated particle with lateral expansions at both ends
      producing a form that resembles a 'doggy-bone'. The particle mass estimated from
      these images agrees with the value of 145 kDa measured by analytical
      ultracentrifugation suggesting 6- to 8-mers. These DivIVA oligomers serve as
      building blocks in the formation of higher order assemblies giving rise to
      strings, wires and, finally, two-dimensional lattices in a time-dependent manner.

PMID- 15165233
TI  - Role of KatG catalase-peroxidase in mycobacterial pathogenesis: countering the
      phagocyte oxidative burst.
AB  - Reactive nitrogen species (RNS) play an essential role in host defence against
      Mycobacterium tuberculosis (MTB) in the mouse model of tuberculosis (TB), as
      evidenced by the increased susceptibility of mice deficient in the inducible
      isoform of nitric oxide synthase (NOS2). In contrast, the role of reactive oxygen
      species (ROS) in protection against MTB is less clear, and mice defective in the
      ROS-generating phagocyte NADPH oxidase (Phox) are relatively resistant. This
      suggests that MTB might possess efficient mechanisms to evade or counter the
      phagocyte oxidative burst, effectively masking the impact of this host defence
      mechanism. In order to assess the role of ROS detoxification pathways in MTB
      virulence, we generated a katG null mutant of MTB, deficient in the KatG catalase
      peroxidase-peroxynitritase, and evaluated the mutant's ability to replicate and
      persist in macrophages and mice. Although markedly attenuated in wild-type
      C57Bl/6 mice and NOS2(-/-) mice, the DeltakatG MTB strain was indistinguishable
      from wild-type MTB in its ability to replicate and persist in gp91(Phox-/-) mice
      lacking the gp91 subunit of NADPH oxidase. Similar observations were made with
      murine bone marrow macrophages infected ex vivo: growth of the DeltakatG MTB
      strain was impaired in macrophages from C57Bl/6 and NOS2(-/-) mice, but
      indistinguishable from wild-type MTB in gp91(Phox-/-) macrophages. These results
      indicate that the major role of KatG in MTB pathogenesis is to catabolize the
      peroxides generated by the phagocyte NADPH oxidase; in the absence of this host
      antimicrobial mechanism, KatG is apparently dispensable.

PMID- 15165234
TI  - The Synechococcus elongatus P signal transduction protein controls arginine
      synthesis by complex formation with N-acetyl-L-glutamate kinase.
AB  - This communication identifies, for the first time, a receptor protein for signal
      perception from the P(II) signal transduction protein in the cyanobacterium
      Synechococcus elongatus. P(II), a phosphoprotein that signals the carbon/nitrogen
      status of the cells, forms a tight complex with the key enzyme of the arginine
      biosynthetic pathway, N-acetylglutamate (NAG) kinase. In complex with P(II), the
      catalytic activity of NAG kinase is strongly enhanced. Complex formation does not
      require the effector molecules of P(II), 2-oxoglutarate and ATP, but it is highly
      susceptible to modifications at the phosphorylation site of P(II), Ser-49. Stable
      complexes were only formed with the non-phosphorylated form of P(II) but not with
      Ser-49 mutants. In accordance with these data, NAG kinase activity in S.
      elongatus extracts correlated with the phosphorylation state of P(II), with high
      NAG kinase activities corresponding to non-phosphorylated P(II) (nitrogen-excess
      conditions) and low activities to increased levels of P(II) phosphorylation
      (nitrogen-poor conditions), thus subjecting the key enzyme of arginine
      biosynthesis to global nitrogen control.

PMID- 15165235
TI  - A complex of the Escherichia coli cell division proteins FtsL, FtsB and FtsQ
      forms independently of its localization to the septal region.
AB  - Three membrane proteins required for cell division in Escherichia coli, FtsQ,
      FtsL and FtsB, localize to the cell septum. FtsL and FtsB, which each contain a
      leucine zipper-like sequence, are dependent on each other for this localization,
      and each of them is dependent on FtsQ. However, FtsQ is found at the cell
      division site in the absence of FtsL and FtsB. FtsQ, in turn, requires FtsK for
      its localization. Here, we show that FtsL, FtsB and FtsQ form a complex in vivo.
      Strikingly, this complex forms in the absence of FtsK, which is required for the
      localization of all three proteins to the mid-cell. These findings indicate that
      the FtsL, FtsB, FtsQ interactions can take place in cells before movement to the
      mid-cell and that migration to this position might occur only after the formation
      of the complex. Evidence indicating the regions of the three proteins involved in
      complex formation is presented. These findings provide the first example of
      preassembly of a subcomplex of cell division proteins before their localization
      to the septal region.

PMID- 15165236
TI  - Regulated site-specific recombination of the she pathogenicity island of Shigella
      flexneri.
AB  - The she pathogenicity island (PAI) is a chromosomal, laterally acquired,
      integrative element of Shigella flexneri that carries genes with established or
      putative roles in virulence. We demonstrate that spontaneous, precise excision of
      the element from its integration site in the 3' terminus of the pheV tRNA gene is
      mediated by an integrase gene (int) and a gene designated rox (regulator of
      excision), both of which are carried on the she PAI. Integrase-mediated excision
      occurs via recombination between a 22 bp sequence at the 3' terminus of pheV and
      an imperfect direct repeat at the pheV-distal boundary of the PAI. Excision leads
      to the formation of a circular episomal form of the PAI, reminiscent of circular
      excision intermediates of other mobile elements that are substrates for lateral
      transfer processes such as conjugation, packaging into phage particles and
      recombinase-mediated integration into the chromosome. The circle junction
      consists of the pheV-proximal and pheV-distal boundaries of the PAI converging on
      a sequence identical to 22 bp at the 3' terminus of pheV. The isolated circle was
      transferred to Escherichia coli where it integrated specifically into phe tRNA
      genes, as it does in S. flexneri, independently of recA. We also demonstrate that
      Rox stimulates, but is not essential for, excision of the she PAI in an integrase
      dependent manner. However, Rox does not stimulate excision by activating the
      transcription of the she PAI integrase gene, suggesting that it has an
      excisionase function similar to that of a related protein from the P4 satellite
      element of phage P2.

PMID- 15165237
TI  - Excision of the high-pathogenicity island of Yersinia pseudotuberculosis requires
      the combined actions of its cognate integrase and Hef, a new recombination
      directionality factor.
AB  - The Yersinia high-pathogenicity island (HPI) encodes the siderophore
      yersiniabactin-mediated iron uptake system. The HPI of Yersinia
      pseudotuberculosis I has previously been shown to be able to excise precisely
      from the bacterial chromosome by recombination between the attB-R and attB-L
      sites flanking the island. However, the nature of the Y. pseudotuberculosis HPI
      excision machinery remained unknown. We show here that, upon excision, the HPI
      forms an episomal circular molecule. The island thus has the ability to excise
      from the chromosome, circularize and reintegrate itself, either in the same
      location or in another asn tRNA copy. We also demonstrate that the HPI-encoded
      bacteriophage P4-like integrase (Int) plays a critical role in HPI excision and
      that, like phage integrases, it acts as a site-specific recombinase that
      catalyses both excision and integration reactions. However, Int alone cannot
      efficiently promote recombination between the attB-R and attB-L sites, and we
      demonstrate that a newly identified HPI-borne factor, designated Hef (for HPI
      excision factor) is also required for this activity. Hef belongs to a family of
      recombination directionality factors. Like the other members of this family, Hef
      probably plays an architectural rather than a catalytic role and promotes HPI
      excision from the chromosome by driving the function of Int towards an
      excisionase activity. The fact that the HPI, and probably several other
      pathogenicity islands, carry a machinery of integration/excision highly similar
      to those of bacteriophages argues for a phage-mediated acquisition and transfer
      of these elements.

PMID- 15165238
TI  - VirA of Agrobacterium tumefaciens is an intradimer transphosphorylase and can
      actively block vir gene expression in the absence of phenolic signals.
AB  - The VirA-VirG two-component system regulates the 30-gene vir regulon in response
      to host-released chemical signals. VirA is a homodimeric membrane-spanning
      histidine protein kinase. Here, we show that mutations in two essential VirA
      residues, His-474 and Gly-657, can be complemented by the formation of mixed
      heterodimers, indicating that each subunit of a VirA dimer transphosphorylates
      the opposite subunit. VirA contains a receiver domain that inhibits kinase
      activity. We use the forced heterodimer system to show that the two receiver
      domains of a VirA dimer act independently and that each inhibits the
      phosphoacceptor subdomain of the opposite subunit. We also demonstrate that
      merodiploid strains co-expressing constitutive VirA mutants and wild-type VirA
      show levels of vir gene expression far lower than haploid strains expressing just
      the constitutive alleles. The fact that wild-type VirA can actively block vir
      gene expression in the absence of phenolic signals suggests that it might have a
      phospho-VirG phosphatase activity. The receiver domain of VirA is essential for
      this activity, whereas residues H474 and G657 of the kinase domain are not
      required. Merodiploid strains co-expressing a constitutive VirA allele and an
      allele that is kinase inactive but proficient in the inhibitory activity show
      strongly inducible vir gene expression, indicating that the inhibitory activity
      is modulated by environmental signals.

PMID- 15165239
TI  - Variation in lipid A structure in the pathogenic yersiniae.
AB  - Important pathogens in the genus Yersinia include the plague bacillus Yersinia
      pestis and two enteropathogenic species, Yersinia pseudotuberculosis and Yersinia
      enterocolitica. A shift in growth temperature induced changes in the number and
      type of acyl groups on the lipid A of all three species. After growth at 37
      degrees C, Y. pestis lipopolysaccharide (LPS) contained the tetra-acylated lipid
      IV(A) and smaller amounts of lipid IV(A) modified with C10 or C12 acyl groups, Y.
      pseudotuberculosis contained the same forms as part of a more heterogeneous
      population in which lipid IV(A) modified with C16:0 predominated, and Y.
      enterocolitica produced a unique tetra-acylated lipid A. When grown at 21 degrees
      C, however, the three yersiniae synthesized LPS containing predominantly hexa
      acylated lipid A. This more complex lipid A stimulated human monocytes to secrete
      tumour necrosis factor-alpha, whereas the lipid A synthesized by the three
      species at 37 degrees C did not. The Y. pestis phoP gene was required for
      aminoarabinose modification of lipid A, but not for the temperature-dependent
      acylation changes. The results suggest that the production of a less
      immunostimulatory form of LPS upon entry into the mammalian host is a conserved
      pathogenesis mechanism in the genus Yersinia, and that species-specific lipid A
      forms may be important for life cycle and pathogenicity differences.

PMID- 15165240
TI  - Unique roles of the rrn P2 rRNA promoters in Escherichia coli.
AB  - In bacteria, genes are often expressed from multiple promoters to allow for a
      greater spectrum of regulation. Transcription of rRNA genes in Escherichia coli
      uses two promoters, rrn P1 and rrn P2. Under the conditions examined previously,
      the P1 and P2 promoters were regulated in response to many of the same changes in
      nutritional conditions. We report here that rrn P2 promoters play unique roles in
      rRNA expression during transitional situations. rrn P2 promoters play a dominant
      role in rRNA synthesis as cells enter into and persist in stationary phase. rrn
      P2 promoters also play a role in the rapid increases in rRNA synthesis that occur
      during outgrowth from stationary phase and during the initial stages of rapid
      shifts to richer media. We demonstrate that rrnB P2 directly senses the
      concentrations of guanosine 5'-disphosphate 3'-diphosphate (ppGpp) and the
      initiating nucleoside triphosphate (iNTP), thereby accounting, at least in part,
      for the observed patterns of regulation. Our work significantly extends previous
      information about the regulators responsible for control of the rrn P2 promoters
      and the relationship between the tandem rRNA promoters.

PMID- 15165242
TI  - Bacteriophage T4 endonuclease II: concerted single-strand nicks yield double
      strand cleavage.
AB  - In vivo, endonuclease II (EndoII) of coliphage T4 cleaves sites with conserved
      sequence elements (CSEs) to both the left and the right of the cleaved bonds, 16
      bp altogether with some variability tolerated. In vitro, however, single-strand
      nicks in the lower strand predominate at sites containing only the left-side CSE
      that determines the precise position of lower strand nicks. Upper strand nick
      positions vary both in vivo and in vitro. A 24 bp substrate was nicked with the
      same precision as in longer substrates, showing that the conserved sequence
      suffices for precise nicking by EndoII. Using DNA ligase in vitro, we found that
      EndoII nicked both strands simultaneously at an in vivo-favoured site but not at
      an in vitro-favoured site. This indicates that the right-side CSE at in vivo
      favoured sites is important for simultaneous nicking of both strands, generating
      double-strand cleavage. Separate analysis of the two strands following in vitro
      digestion at two in vitro-favoured sites showed that EndoII nicked the lower
      strand about 1.5-fold faster than the upper strand. In addition, the upper and
      lower strands were nicked independently of each other, seldom resulting in double
      strand cleavage. Thus, cleavage by EndoII is the fortuitous outcome of two
      separate nicking events.

PMID- 15165241
TI  - The quormone degradation system of Agrobacterium tumefaciens is regulated by
      starvation signal and stress alarmone (p)ppGpp.
AB  - A unique signal degradation system has recently been discovered in Agrobacterium
      tumefaciens. Upon entering stationary phase, A. tumefaciens terminates quorum
      sensing-dependent Ti-plasmid conjugation by degradation of acyl homoserine
      lactone (AHL) quormone via the enzyme AttM (AHL-lactonase). attM, together with
      attK and attL, constitute one transcriptional unit subjected to the control of a
      common promoter. AttJ, the other member of the signal degradation system, is an
      IclR-like negative transcriptional factor, which tightly represses the expression
      of AttM at the early stage of bacterial growth. In this study, we found that this
      quormone degradation system is activated by either carbon or nitrogen starvation.
      Quormone degradation was significantly delayed when bacterial culture was
      supplemented with extra carbon or nitrogen source in the nutrient-limited minimal
      medium before the onset of stationary phase. To identify the signalling pathway
      and regulatory mechanisms that mediate quormone degradation, we constructed a
      reporter strain A6(attKLM::lacZ) in which the promoterless lacZ was
      transcriptionally fused to the attKLM promoter. Transposon mutagenesis of strain
      A6(attKLM::lacZ) led to identification of the relA gene, which encodes the stress
      alarmone (p)ppGpp synthetase. Tn5 knock-out of relA abolished the stationary
      phase-dependent expression of attM. We concluded that the A. tumefaciens quormone
      degradation system is coupled to and regulated by the generic (p)ppGpp stress
      response machinery.

PMID- 15165243
TI  - Sed1p and Srl1p are required to compensate for cell wall instability in
      Saccharomyces cerevisiae mutants defective in multiple GPI-anchored
      mannoproteins.
AB  - The covalently linked cell wall protein Ccw12p of Saccharomyces cerevisiae is a
      GPI-anchored protein (V. Mrsa et al., 1999, J Bacteriol 181: 3076-3086). Although
      only 121 amino acids long, the haemagglutinin-tagged protein released by
      laminarinase from the cell wall possesses an apparent molecular mass of > 300
      kDa. A membrane-bound form with an apparent molecular mass of 58 kDa is highly O-
      and N-glycosylated and contains the GPI anchor. With a half-life of 2 min, the
      membrane form is transformed to the > 300 kDa form. The deletion mutant
      ccw12Delta grows slower than the wild type, is highly sensitive to Calcofluor
      white and contains 2.5 times more chitin. Further, compared with wild-type yeast,
      significantly more proteins are released from intact cells when treated with
      dithiothreitol. Interestingly, these defects become less pronounced when further
      GPI-anchored cell wall proteins are deleted. Mutant DeltaGPI (simultaneous
      deletion of CCW12, CCW13/DAN1, CCW14, TIP1 and CWP1) is similar in many respects
      to wild-type yeast. To find out how the cell wall is stabilized in mutant
      DeltaGPI, a genome-wide transcription analysis was performed. Of 159
      significantly regulated genes, 14 encode either known or suspected cell wall
      associated proteins. Analysis of genes affected in transcription revealed that
      SED1 and SRL1 in particular are required to reconstruct cell wall stability in
      the absence of multiple GPI-anchored mannoproteins.

PMID- 15165244
TI  - Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of
      the intracellular oxidant concentration.
AB  - The transcription factor Pap1 and the MAP kinase Sty1 are key regulators of
      hydrogen peroxide-induced responses in Schizosaccharomyces pombe. Pap1 can be
      activated quickly at low, but not high, hydrogen peroxide concentrations. The MAP
      kinase Sty1 has been reported to participate in Pap1 activation by the oxidant.
      Here, we provide biochemical and genetic evidence for the in vivo formation of a
      hydrogen peroxide-induced disulphide bond in Pap1, which precedes the rapid and
      reversible nuclear accumulation of the transcription factor. We show that
      activation of the Sty1 cascade before the oxidative insult, or overexpression of
      the Sty1-regulated genes ctt1 (encoding catalase) or gpx1 (encoding glutathione
      peroxidase), can accelerate Pap1 entry even at high doses of hydrogen peroxide.
      In fact, the lack of Sty1 impedes Pap1 nuclear localization, but only at high
      doses of the oxidant. We propose that, whereas low doses of hydrogen peroxide
      lead directly to Pap1 oxidation-activation, high concentrations of the oxidant
      initially activate the Sty1 pathway, with the consequent increase in scavenging
      enzymes, which in turn helps to decompose the excess of hydrogen peroxide and
      achieve an appropriate concentration for the subsequent activation of Pap1. Our
      results also suggest that activation of Sty1 at high doses of hydrogen peroxide
      may also be required to trigger other antioxidant activities such as those
      reverting the overoxidation of cysteine residues at the Pap1 pathway.

PMID- 15165245
TI  - Calcium measurement in living filamentous fungi expressing codon-optimized
      aequorin.
AB  - Calcium signalling is little understood in filamentous fungi largely because easy
      and routine methods for calcium measurement in living hyphae have previously been
      unavailable. We have developed the recombinant aequorin method for this purpose.
      High levels of aequorin expression were obtained in Neurospora crassa,
      Aspergillus niger and Aspergillus awamori by codon optimization of the aequorin
      gene. Three external stimuli (mechanical perturbation, hypo-osmotic shock and
      high external calcium) were found transiently to increase [Ca(2+)](c). Each of
      the calcium signatures associated with these physico-chemical treatments was
      unique, suggesting the involvement of three distinct calcium-mediated signal
      transduction pathways. The fungal calcium channel blocker KP4 inhibited the
      [Ca(2+)](c) responses to hypo-osmotic shock and high external calcium, but not to
      mechanical perturbation. The divalent cation chelator BAPTA inhibited [Ca(2+)](c)
      responses to mechanical perturbation and hypo-osmotic shock. The calcium agonists
      A23187 and cyclopiazonic acid increased [Ca(2+)](c) levels.

PMID- 15165247
TI  - The RING-finger domain of the fungal repressor crgA is essential for accurate
      light regulation of carotenogenesis.
AB  - Mucor circinelloides responds to blue light by activating the biosynthesis of
      carotenoids. Gene crgA acts as a repressor of this light-regulated process, as
      its inactivation leads to overaccumulation of carotenoids in both the dark and
      the light. The predicted CrgA protein contains different recognizable structural
      domains, including a RING-finger zinc-binding motif, several glutamine-rich
      regions, a putative nuclear localization signal and an isoprenylation domain. To
      gain insight into the specific mode of action of the CrgA protein, we sought to
      define the CrgA domains critical for the light regulation of carotenogenesis. For
      this, mutant crgA alleles harbouring missense or deletion mutations in conserved
      residues of those domains were generated, and their functionality was assessed by
      testing their ability to complement a null crgA mutation. Point mutations of the
      amino-terminal RING-finger domain abrogated the ability of CrgA to repress
      carotenogenesis in the dark, as did the deletion of a poly glutamine-rich region
      at the carboxyl domain of CrgA. In contrast, mutations of the isoprenylation
      domain only slightly affected the CrgA function in carotenogenesis. The results
      identify two functional domains presumably involved in protein-protein
      interaction in the CrgA protein and suggest a role for the ubiquitin-proteasome
      pathway in the light regulation of carotenogenesis in fungi.

PMID- 15165246
TI  - Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic
      rearrangements and tetraploid formation.
AB  - One hundred and twenty Candida albicans clinical isolates from the late 1980s and
      early 1990s were examined for homozygosity at the MTL locus. Of these, 108 were
      heterozygous (MTLa/MTLalpha), whereas seven were MTLa and five were MTLalpha.
      Five of the homozygous isolates were able to switch to the opaque cell
      morphology, while opaque cells were not detectable among the remaining seven.
      Nevertheless, all but one of the isolates homozygous at the MTL locus were shown
      to mate and to yield cells containing markers from both parents; the non-mater
      was found to have a frameshift in the MTLalpha1 gene. In contrast to
      Saccharomyces cerevisiae, C. albicans homozygotes with no active MTL allele
      failed to mate rather than mating as a cells. There was no correlation between
      homozygosity and fluconazole resistance, mating and fluconazole resistance or
      switching and fluconazole resistance, in part because most of the strains were
      isolated before the widespread use of this antifungal agent, and only three were
      in fact drug resistant. Ten of the 12 homozygotes had rearranged karyotypes
      involving one or more homologue of chromosomes 4, 5, 6 and 7. We suggest that
      karyotypic rearrangement, drug resistance and homozygosity come about as the
      result of induction of hyper-recombination during the infection process; hence,
      they tend to occur together, but each is the independent result of the same
      event. Furthermore, as clinical strains can mate and form tetraploids, mating and
      marker exchange are likely to be a significant part of the life cycle of C.
      albicans in vivo.

PMID- 15165248
TI  - Characterization of the MerD protein from Ralstonia metallidurans CH34: a
      possible role in bacterial mercury resistance by switching off the induction of
      the mer operon.
AB  - MerD and MerR from Tn4378 found in Ralstonia metallidurans CH34 were purified to
      homogeneity after overexpression in Escherichia coli. Using electrophoretic
      mobility shift assays and footprinting experiments, we found that MerD cannot
      bind to DNA. However, in vitro MerD can form a ternary complex in association
      with merOP and MerR. The presence of MerD in this complex was demonstrated by
      Western analysis with antibodies to MerD. To our knowledge, this is the first
      description of such a ternary complex between MerD-MerR and DNA. The formation
      and stability of this ternary complex are dependent on the relative concentration
      of the two proteins and modulated by the presence of mercury. We postulate that
      MerD could displace Hg-bound MerR from the mer operator to allow new synthesis of
      metal-free MerR able to switch off the induction of the mer genes when the
      external mercury is exhausted. This could fully explain how MerD can be a co
      regulator repressing the induction of the mer operon.

PMID- 15165249
TI  - Cleavage-dependent activation of a chlamydia-secreted protease.
AB  - A chlamydia-secreted protein designated CPAF (chlamydial proteasome-like activity
      factor) was shown previously to degrade host transcriptional factors (e.g. RFX5)
      required for major histocompatibility (MHC) gene activation. Although CPAF is
      encoded by a single open reading frame (ORF) in the chlamydial genome, two
      fragments designated CPAFn and CPAFc were the main products purified. The current
      study was designed to test whether cleavage of CPAF into CPAFn and CPAFc is a
      physiological process required for CPAF proteolytic activity. Pulse-chase
      experiments revealed that CPAF was initially synthesized in chlamydia-infected
      cells as a 70 kDa full-length protein and rapidly cleaved into CPAFn and c
      fragments. Full-length CPAF expressed via a transgene in mammalian cells remained
      uncleaved and had no proteolytic activity, whereas CPAF expressed in Escherichia
      coli cells was processed and possessed RFX5 degradation activity. CPAF mutants
      deficient in processing even when expressed by E. coli failed to degrade RFX5.
      More importantly, the RFX5 degradation activity was partially restored when the
      mutant CPAF was artificially induced to undergo cleavage. These observations
      together have demonstrated that cleavage of CPAF is both necessary and sufficient
      for CPAF activity.

PMID- 15165250
TI  - The FNR-type transcriptional regulator SinR controls maturation of Agrobacterium
      tumefaciens biofilms.
AB  - Agrobacterium tumefaciens is a plant pathogen that persists as surface-associated
      populations on plants or soil particles. A genetic screen for A. tumefaciens
      mutants deficient for surface interactions identified a mutant that forms thin,
      sparsely populated biofilms, but is proficient for initial attachment. The mutant
      is disrupted in a gene designated sinR, encoding a member of the DNR subfamily of
      FNR-type transcription regulators. SinR is required for normal maturation of A.
      tumefaciens biofilms on both inert surfaces and plant tissues, and elevated sinR
      expression results in accelerated biofilm formation. Expression of sinR is
      increased close to 30-fold in cultures grown in oxygen-limited environments and
      is also induced within biofilms grown under oxic conditions. A consensus FNR box,
      the presumptive binding site for FNR-type proteins, is located upstream of the
      sinR promoter. FnrN, a second A. tumefaciens FNR-like regulator, is required for
      induction of sinR in oxygen-limited cultures, whereas SinR negatively influences
      its own expression. FnrN influences biofilm formation, but its effects are less
      dramatic than those of SinR. We propose a model in which a signal cascade,
      responsive to oxygen limitation and initiated by FnrN, activates sinR expression
      in response to decreased oxygen levels, and influences the formation of A.
      tumefaciens biofilms.

PMID- 15165251
TI  - The major structural components of two cell surface filaments of Porphyromonas
      gingivalis are matured through lipoprotein precursors.
AB  - Bacterial cell surface filaments play significant roles in adherence to and
      invasion of host cells. They are generated by the chaperone/usher pathway system
      (class I fimbriae), the type II secretion system (type IV pili) and the
      nucleation-dependent polymerization system (Curli filaments) that are categorized
      by their modes of expression and assembly. In this study, we found that the
      periodontal pathogen Porphyromonas gingivalis expressed the major structural
      components of two cell surface filaments (fimbrilin and the 75 kDa protein) that
      had extremely long prosequences in their primary gene products. N-terminal amino
      acid sequencing of the prosequences, treatment of P. gingivalis cells with
      globomycin, an inhibitor for lipoprotein-specific signal peptidase, amino acid
      substitution of the cysteine residue of the prosequence of fimbrilin and [(3)H]
      palmitic acid labelling implied that fimbrilin and the 75 kDa protein were
      matured through their lipoprotein precursor forms. Accumulation of precursor
      forms of fimbrilin and the 75 kDa protein on the cell surface of the gingipain
      null mutant revealed that Arg-gingipain processed these precursors on the surface
      to yield their mature forms, which subsequently assembled into the filamentous
      structures, suggesting that the transport and assembly of the major component
      proteins appear to be novel.

PMID- 15165253
TI  - Inactivation of Helicobacter pylori cagA gene affects motility.
AB  - BACKGROUND: The cytotoxin-associated protein CagA is a Helicobacter pylori
      immunodominant antigen whose gene resides in the cag pathogenicity island. Our
      purpose was to determine if the disruption or deletion of cagA gene could have an
      effect on the expression of other proteins at the proteome level. We analyzed two
      H. pylori strains, 328 and G27 wild-type, bearing the cag pathogenicity island,
      and their respective isogenic cagA(-) mutants. METHODS: The proteomes of two H.
      pylori strains (328 and its isogenic mutant SPM328_DeltacagA) were resolved by
      two-dimensional electrophoresis and the digitalized images obtained were analysed
      both quantitatively and qualitatively. Peculiar spots of each strain were
      identified by mass spectrometry or by Western blotting. RESULTS: The comparison
      between the proteome expression of an H. pylori cagA(+) strain and an isogenic
      mutant strain where the cagA gene was disrupted showed that, as well as the lack
      of expression of CagA, both flagellin A and flagellin B expressions were
      significantly decreased. The cagA(-) isogenic mutant was nonmotile.
      G27_DeltacagA, in which CagA was inactivated by gene deletion, was nonmotile as
      well respecting to motile G27 wild-type strain. Moreover, reintroduction of cagA
      in G27_DeltacagA restored motility. CONCLUSIONS: Our results suggest that CagA
      could quantitatively influence flaA and flaB transcription or their subsequent
      translation and/or correct folding.

PMID- 15165254
TI  - Serum antibodies to Helicobacter pylori and its heat-shock protein 60 correlate
      with the response of gastric mucosa-associated lymphoid tissue lymphoma to
      eradication of H. pylori.
AB  - BACKGROUND AND AIMS: Eradication of Helicobacter pylori leads to regression of
      mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we measured
      serum antibodies to H. pylori and H. pylori-recombinant heat-shock protein 60
      (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral
      immune responses to the bacterial antigens correlate with the efficacy of
      eradication therapy. METHODS: Serum samples were obtained from 33 patients with
      H. pylori-positive gastric MALT lymphoma before undergoing therapy to eradicate
      the bacteria. Anti-H. pylori antibodies were measured in a commercial assay and
      in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain.
      RESULTS: Helicobacter pylori were eradicated in all 33 patients, and the lymphoma
      completely regressed histologically in 26 patients (79%). Pre-treatment titers of
      serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed
      were significantly higher than titers in patients whose tumors did not regress (p
      =.0011 and.035, respectively). By logistic regression analysis, age (odds ratio =
      0.88, 95% confidence interval = 0.80-0.99), endoscopic appearance (0.053, 0.004
      0.65), titers of anti-H. pylori antibodies (67.6, 2.5-1800), and titers of anti
      rHSP60 antibody (6.4, 1.2-36) were identified as significantly associated factors
      with the outcome of MALT lymphoma. CONCLUSIONS: Measurement of serum antibodies
      to H. pylori and HSP60 might be useful for predicting the response of gastric
      MALT lymphoma to eradication of H. pylori.

PMID- 15165255
TI  - Increased production of matrix metalloproteinases in Helicobacter pylori
      associated human gastritis.
AB  - BACKGROUND AND AIMS: Helicobacter pylori infection results in an active, chronic
      inflammation of the gastric mucosa. Previous studies have highlighted the
      importance of matrix metalloproteinases (MMPs) in diseases involving mucosal
      inflammation, prompting us to investigate MMP activity in H. pylori-induced
      gastritis. METHODS: Gastric biopsies were obtained from H. pylori-infected and
      uninfected volunteers, and MMP activity was assessed using substrate gel
      electrophoresis. MMP production was also evaluated by immunohistochemistry and
      real time-polymerase chain reaction. In parallel, tissue inhibitors of MMPs
      (TIMP) levels and TIMP-MMP complexes were examined in corresponding tissues using
      enzyme-linked immunosorbent assays and Western blotting. Finally, MMP production
      by gastric macrophages was determined after stimulation with H. pylori. RESULTS:
      Antral mucosa of H. pylori-infected subjects demonstrated a 19-fold higher MMP-9
      activity than that of uninfected individuals. MMP-2 was present at lower levels,
      but was also increased in H. pylori-infected individuals, while there was no
      difference in the total levels of TIMP-1 and TIMP-2 between the groups of
      volunteers. Significant numbers of MMP-9-containing cells were only found in the
      H. pylori-infected antral mucosa. Tissue-resident macrophages were significantly
      increased in H. pylori-infected individuals, and double-staining showed MMP-9
      colocalized to macrophages. Furthermore, gastric macrophages secreted MMP-9 in
      response to H. pylori bacteria. A corresponding 10-fold increase of gene
      expression of MMP-9 was seen in patients infected with H. pylori compared to
      uninfected individuals. CONCLUSIONS: Helicobacter pylori infection results in a
      substantial increase in MMP-9 and MMP-2 activity in the gastric mucosa, probably
      contributed to in large part by tissue-resident macrophages, while no changes
      were seen in the TIMP levels. The net increase in gastric MMP activity is likely
      to contribute to tissue damage during H. pylori-associated gastritis.

PMID- 15165256
TI  - Absence of catalase reduces long-term survival of Helicobacter pylori in
      macrophage phagosomes.
AB  - BACKGROUND: Some Helicobacter pylori strains can survive within macrophage
      phagosomes for up to 24 hours. The factors that play a role in this survival
      remain ill-defined. Therefore, the contribution of catalase in mediating the
      survival of H. pylori following phagocytosis was investigated in vitro. METHODS:
      An isogenic, catalase-deficient strain of H. pylori was generated and tested for
      sensitivity to hydrogen peroxide and susceptibility to macrophage-mediated
      killing. RESULTS: The isogenic, catalase-deficient strain of H. pylori was
      effectively killed by hydrogen peroxide within 3 minutes compared to wild-type H.
      pylori which maintained 100% survival up to 21 minutes. The catalase-deficient
      mutant was also significantly more susceptible to macrophage-mediated killing
      than the parent strain, even when the ratio of bacteria to macrophage was
      increased. CONCLUSION: These results indicate that although some strains of H.
      pylori are capable of survival within the macrophage phagosome, survival is
      dependent on virulence factors such as catalase for evasion of innate host
      defense.

PMID- 15165257
TI  - Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced
      gastritis in mongolian gerbils.
AB  - BACKGROUND AND AIMS: Helicobacter pylori infection causes chronic gastritis and
      leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal
      barrier could be involved in these processes. Our aim was to investigate gastric
      barrier function in H. pylori-induced gastritis. METHODS: Stripped gastric
      mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks
      after inoculation, respectively) and controls were mounted in Ussing chambers.
      (51)Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein
      antigen) were used to assess mucosal barrier function. The electrophysiological
      parameters of the mucosa (transepithelial potential, short circuit current, and
      transepithelial resistance) were monitored as measurements of barrier integrity
      and viability. Tissue histology was performed to assess inflammation. RESULTS: In
      the antrum, both short-term gastritis [4.68 (3.88-5.74) x 10(-6) vs. control 2.86
      (2.34-3.77) x 10(-6) cm/s, p <.001] and gastritis of long-standing [5.72 (3.88
      10.94) x 10(-6) cm/s, p <.001 vs. control] showed increased permeability to
      (51)Cr-EDTA. In long-standing antral gastritis there was also an increased HRP
      flux [9.01 (2.98-45.02) vs. control 0.52 (0.06-1.20) pmol/h/cm(2), p <.001]. In
      the corpus, permeability to (51)Cr-EDTA was increased only in long-standing
      gastritis [4.63 (3.64-7.45) x 10(-6) vs. control 2.86 (2.12-3.98) x 10(-6) cm/s,
      p <.01]. Gastric mucosal permeability to (51)Cr-EDTA was correlated to
      histological inflammation and inflammatory activity. The levels of serum anti-H.
      pylori immunoglobulin G were positively correlated to HRP flux and (51)Cr-EDTA
      permeation. CONCLUSIONS: Helicobacter pylori-induced gastritis in Mongolian
      gerbils was associated with a long-standing gastric mucosal barrier dysfunction.
      The barrier defect extended from the antrum into the corpus over time. This
      impaired barrier function may contribute to perpetuation of chronic inflammation
      and may be involved in H. pylori-associated carcinogenesis.

PMID- 15165258
TI  - Novel monoclonal antibody-based Helicobacter pylori stool antigen test.
AB  - BACKGROUND: A number of noninvasive tests have been developed to establish the
      presence of Helicobacter pylori infection. Although polyclonal antibody-based
      stool antigen testing has a good sensitivity and specificity, it is less accurate
      than urea breath testing. Recently, a monoclonal antibody-based stool antigen
      test demonstrated an excellent performance in diagnosing H. pylori infection in
      adults and in pediatric populations. AIM: To evaluate the diagnostic accuracy of
      a novel stool test based on monoclonal antibodies to detect H. pylori antigens in
      frozen human stool in the pretreatment setting. PATIENTS AND METHODS: Stool
      specimens were prospectively collected from 78 patients undergoing gastroscopy
      and stored at -20 degrees C until tested. Helicobacter pylori infection was
      evaluated by histology, rapid urease testing and urea breath tests ((13)C-UBT).
      Positivity of the three tests was considered the gold standard for H. pylori
      active infection. Patients with no positive test were considered negative. The
      gold standard was compare to the results of the monoclonal antibody stool antigen
      test. Frozen stool specimens were tested using a novel monoclonal-antibody-based
      enzyme immunoassay (HePy-Stool, Biolife-Italiana, Milan, Italy). RESULTS: The
      sensitivity and specificity of the monoclonal stool antigen test were 97%[95%
      confidence interval, (CI) 86-100] and 94% (95% CI: 81-99), respectively. Negative
      and positive predictive values were 97% (95% CI: 85-99), and 95% (95% CI: 83-99),
      respectively. The diagnostic accuracy was 96% (95% CI: 88-99). The likelihood
      ratio for a positive test was 17 and for a negative test was 0. CONCLUSIONS:
      Although the (13)C-UBT is the most accurate among the available noninvasive
      tests, our results show that an H. pylori stool test using monoclonal antibody
      might be an excellent alternative.

PMID- 15165259
TI  - Helicobacter pylori infection in children in Estonia: decreasing seroprevalence
      during the 11-year period of profound socioeconomic changes.
AB  - BACKGROUND: The prevalence of Helicobacter pylori infection is inversely
      associated with socioeconomic conditions in childhood. In Estonia, a high
      prevalence of H. pylori infection has been observed among children born in 1987
      and earlier. Since 1991, after the dissolution of the USSR, profound social and
      economic changes have taken place in the country. The aim of the study was to
      evaluate changes in the seroprevalence of H. pylori infection among children in
      the period 1991-2002. MATERIALS AND METHODS: The hospital-based study population
      consisted of two groups of children enrolled in 1991 (n = 425) and 2002 (n = 296)
      according to the same inclusion criteria. The immunoglobulin G antibodies to the
      cell surface proteins of H. pylori were determined by enzyme-linked immunosorbent
      assay, and the sera with the borderline results were analyzed by immunoblot
      analysis. Multiple regression analysis was used to determine the associations
      between H. pylori seropositivity and different variables such as demographic
      characteristics, diagnoses and year of enrollment. RESULTS: The only two
      variables linked independently to H. pylori serostatus were age and year of
      enrollment: the adjusted odds of being H. pylori seropositive were 1.92 [95%
      confidence interval (CI) 1.33-2.76] times higher for the children enrolled in
      1991 compared with the children enrolled in 2002. The age-standardized
      seroprevalence rate was 42.2% (95% CI 37.4-47.0%) for the group of 1991 and 28.1%
      (95% CI 23.1-33.6%) for the group of 2002. CONCLUSION: The prevalence of H.
      pylori infection among children has significantly decreased during the 11-year
      period of profound socioeconomic changes in Estonia.

PMID- 15165260
TI  - Helicobacter pylori infection in Turkish children: comparison of diagnostic
      tests, evaluation of eradication rate, and changes in symptoms after eradication.
AB  - BACKGROUND: Helicobacter pylori infection is most frequently acquired in
      childhood. After this organism is eradicated, the rate of reinfection is low.
      Thus, it is very important to diagnose and treat the disease appropriately in
      childhood, and to be able to assess eradication with certainty. Eradication of H.
      pylori infection is reported to reduce or eliminate abdominal pain and dyspeptic
      symptoms in children. PATIENTS AND METHODS: The study involved 102 children who
      had already been diagnosed with symptomatic H. pylori infection based on gastric
      histopathological examination, urea breath test, rapid urease test, serology and
      culture. Each patient's symptoms and family history of gastrointestinal problems
      were recorded. Using histology as the gold standard for identifying H. pylori
      infection, we determined the diagnostic sensitivity of each of the other methods.
      Omeprazole or lansoprazole, amoxicillin and clarithromycin were administered as
      eradication treatment, and each patient was re-evaluated by urea breath test 8
      weeks later. Each child was re-interviewed about symptoms after treatment. These
      answers and the results of drug sensitivity testing were recorded. Cases of
      failed eradication were re-treated with a quadruple-drug regimen of tetracycline,
      metronidazole, bismuth subsalicylate and omeprazole. RESULTS: The most frequent
      symptom was abdominal pain (89.2%). Fifty-four per cent of the subjects had a
      family history of dyspeptic symptoms. Sixty-six patients (64.7%) exhibited
      nodularity in the antral mucosa. The sensitivities of the diagnostic tests in
      histologically proven cases were as follows: urea breath test 100%, rapid urease
      test 89.2%, serology 71.9%, and culture 54.9%. Metronidazole had the highest
      frequency of resistance (36.4%) and the rate of clarithromycin resistance was
      18.2%. The eradication rate after first-line therapy was 75.5%, and abdominal
      pain and dyspeptic symptoms were reduced or completely resolved in 75.7% of the
      successful-eradication cases. The proportion of failed-eradication cases that
      responded well to quadruple-drug therapy was 93.8%. CONCLUSION: Symptomatic H.
      pylori infection in a child should always be treated. The urea breath test is an
      accurate and reliable way to identify H. pylori-positive patients and to
      determine the response to treatment. Triple-agent therapy is effective for
      eradicating H. pylori infection in children and usually helps reduce or eliminate
      dyspeptic symptoms. The level of H. pylori resistance to metronidazole is high in
      our region. The significant rate of resistance to clarithromycin (18.1%) may
      explain the treatment failure observed in this study.

PMID- 15165261
TI  - The prevalence of peptic ulcer not related to Helicobacter pylori or non
      steroidal anti-inflammatory drug use is negligible in southern Europe.
AB  - BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer
      disease, but the proportion of H. pylori-negative peptic ulcers seems to be
      increasing in developed countries. We investigated the frequency of H. pylori
      negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs
      (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We
      prospectively collected consecutive patients with an endoscopically verified
      active peptic ulcer over 6 months from different areas of Spain. Helicobacter
      pylori infection was assessed by rapid urease test and histologic examination
      (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori
      was not detected with the invasive test. Patients were considered H. pylori
      negative if all three tests were negative. NSAID use was determined by structured
      data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%)
      were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472
      patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and
      only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193
      patients had benign gastric ulcers and 87% (n = 168) of them were infected by H.
      pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric
      ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001).
      Consequently, the frequency of H. pylori-negative gastric ulcer in patients not
      using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly
      associated with H. pylori infection in southern Europe, and only 1.6% of all
      duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H.
      pylori infection or NSAID use.

PMID- 15165263
TI  - Age at acquisition of Helicobacter pylori infection: comparison of two areas with
      contrasting risk of gastric cancer.
AB  - BACKGROUND: Helicobacter pylori infection is usually acquired during childhood
      and is a known risk factor for the development of gastric malignancies in
      adulthood. It has been reported that early age at first infection may determine a
      neoplastic outcome in adults. The purpose of this study was to determine the
      prevalence of Helicobacter pylori infection in children residing in areas with
      high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate
      whether differences in the age of acquisition of H. pylori infection were present
      in the two populations. MATERIALS AND METHODS: The study sample was based on a
      census taken in 1999. Using the (13)C-urea breath test, we compared the
      prevalence of H. pylori infection among children aged 1-6 years. RESULTS: Among
      345 children in Pasto, 206 (59.7%) were H. pylori-positive, compared with 188
      (58.6%) among 321 children in Tumaco. The two populations share a common pattern
      of very early age at infection and marked increase in prevalence during the first
      4 years of life. No differences in any one year were observed when comparing the
      two groups. CONCLUSIONS: The prevalence of infection was similarly high and
      increased with age in both populations. In these populations the age of
      acquisition of H. pylori after 1 year of age does not appear to be a primary
      factor responsible for the differences in the rates of gastric cancer incidence
      in adults. Previous findings in adults showed lower prevalence of the most
      virulent genotypes in Tumaco compared to Pasto, and bacterial virulence may play
      a key role in determining cancer outcome.

PMID- 15165262
TI  - Efficacy of two rabeprazole/gatifloxacin-based triple therapies for Helicobacter
      pylori infection.
AB  - OBJECTIVES: To evaluate the efficacy of two novel treatment regimens consisting
      of gatifloxacin (400 mg daily), amoxicillin (1 g twice daily), and rabeprazole 20
      mg once (RAG20) or twice daily (RAG40) given for 7 days in the eradication of
      Helicobacter pylori. METHODS: Eligible patients undergoing endoscopy and having a
      positive rapid urease assay for H. pylori were enrolled in this open-label trial.
      Gastric biopsies from a random cohort of patients were cultured for H. pylori and
      in vitro susceptibility to gatifloxacin and amoxicillin was performed using the E
      test. Compliance and side-effects were evaluated by phone calls. (14)C-urea
      breath tests were performed a minimum of 4 weeks after therapy and 3 weeks after
      any acid suppressive therapy. RESULTS: A total of 104 patients, 52 in each group
      (40 females and 64 males; mean age 45.7 years) were enrolled sequentially.
      Eradication occurred in 43 out of 52 patients in RAG20 group (both per-protocol
      and intention-to-treat analysis: 83%; 95% CI: 72-93%) and in 48 of 52 patients in
      the RAG40 group (both per-protocol and intention-to-treat analysis: 92%; 95% CI:
      85-99%). Seven patients in the RAG40 group who had previously failed one or more
      treatment regimens for H. pylori were cured. No significant adverse effects were
      reported. All 50 recovered H. pylori strains were susceptible to amoxicillin and
      gatifloxacin in vitro. CONCLUSIONS: A 7-day regimen of gatifloxacin-rabeprazole
      amoxicillin is effective eradication therapy for H. pylori. The use of
      rabeprazole twice daily results in superior eradication rates including cases of
      failed primary therapy. This new regimen is simple, well-tolerated, and may lead
      to higher compliance and lower costs.

PMID- 15165265
TI  - Lower prevalence of Helicobacter pylori infection in patients with inflammatory
      bowel disease but not with chronic obstructive pulmonary disease - antibiotic use
      in the history does not play a significant role.
AB  - BACKGROUND: Patients with inflammatory bowel disease have lower prevalence of
      Helicobacter pylori infection, but the exact reason for this is not yet clear.
      AIM: To examine whether the antibiotics frequently used in inflammatory bowel
      disease are responsible for the lower prevalence of H. pylori infection. Patients
      with chronic obstructive pulmonary disease on prolonged previous antibiotic
      therapy were used for comparison. METHODS: Presence/absence of H. pylori
      infection was detected by a (13)C-urea breath test in 133 patients with
      inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and
      compared with that of 135 patients with chronic obstructive pulmonary disease and
      with two age-matched control groups (200 patients each). Primary disease
      location, duration of disease and detailed analysis of previous and current
      medication (dose and duration of antibiotics, steroids, 5-aminosalicylic acid)
      were analysed in each cases. RESULTS: Seventeen of the 133 patients with
      inflammatory bowel disease [12.2% (10/82) of ulcerative colitis and 13.7% (7/51)
      of Crohn's disease] and 90/135 patients with chronic obstructive pulmonary
      disease (66.7%) were positive for H. pylori. A total of 78/200 (39%) for the
      inflammatory-bowel-disease-group-matched controls and 110/210 (55%) for the
      chronic-obstructive-pulmonary-disease-matched controls were positive for H.
      pylori. The history of any antibiotic or steroid therapy had no influence on H.
      pylori status of patients with inflammatory bowel disease. CONCLUSION: The
      prevalence of H. pylori compared to the age-matched controls is significantly
      lower in patients with inflammatory bowel disease but not in those with chronic
      obstructive pulmonary disease. Antibiotic use is not responsible for the lower
      prevalence of H. pylori infection in patients with inflammatory bowel disease.

PMID- 15165264
TI  - Is the association between Helicobacter pylori and gastric cancer confined to
      CagA-positive strains?
AB  - BACKGROUND: Infection with Helicobacter pylori is associated with an increased
      risk of gastric cancer. Several studies have indicated that the association
      differs with strain type. We aimed to find out if infection with strains lacking
      the virulence factor CagA is linked to gastric cancer risk. MATERIALS AND
      METHODS: In a hospital-based case-control study, we collected sera from 100 case
      patients with a newly diagnosed gastric adenocarcinoma and 96 control patients
      with diseases unrelated to H. pylori status. Antibodies to H. pylori were
      analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA
      were detected by immunoblot. Logistic regression was used to obtain odds ratios
      (ORs) as estimates of relative risk, adjusted for potential confounding. RESULTS:
      Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA.
      The corresponding numbers among the controls were 58% and 55%, respectively.
      ELISA positivity was associated with an increased risk of gastric adenocarcinoma
      compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95%
      CI 1.9-8.2). The OR was 7.4 (95% CI 3.3-16.6) for CagA-positive relative to CagA
      negative subjects. Among ELISA-positive subjects the presence of CagA antibodies
      increased the risk 3.6 times (95% CI 1.2-11.1). ELISA-positive CagA-negative
      infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0
      17.0) compared to no infection (ELISA-negative and CagA-negative). CONCLUSIONS:
      Although patients with antibodies to CagA have the greatest risk of developing
      gastric cancer, those with CagA-negative infections run a significantly greater
      risk than uninfected persons.

PMID- 15165266
TI  - Is there any relation between Helicobacter pylori infection and iron deficiency
      anemia in children with celiac disease?

PMID- 15165268
TI  - Liquid-based cytology: applying international experience to the United Kingdom.

PMID- 15165269
TI  - Peritoneal washing cytology.
AB  - Peritoneal washing cytology (PWC) is a useful indicator of ovarian surface
      involvement and peritoneal dissemination by ovarian tumours. It may identify
      subclinical peritoneal spread and thus provide valuable staging and prognostic
      information, particularly for non-serous ovarian tumours. The role of PWC as a
      prognostic indicator for endometrial carcinoma is less clear, due in part to the
      questionable significance of identifying endometrial tumour cells in the
      peritoneum. Detection of metastatic carcinoma in PWC is based on the recognition
      of non-mesothelial cell characteristics. However a number of conditions such as
      reactive mesothelial cells, endometriosis and endosalpingiosis may mimic this
      appearance. Cells from these conditions may have a similar presentation in PWC to
      that of serous borderline tumours and low-grade serous carcinoma. The presence of
      cilia, lack of single atypical cells, prominent cytoplasmic vacuolation, marked
      nuclear atypia or two distinct cell populations are features favouring a benign
      process. Attention to these features along with close correlation with clinical
      history and the results of surgical pathology should help avoid errors.
      Additional assistance may be provided by the use of cell blocks and special
      stains.

PMID- 15165270
TI  - Women's interpretation of cervical smear test results.
AB  - Screening for cervical cancer using the Papanicolaou smear test has been
      available in England since the 1960s, yet very little is known about how women
      interpret their test results. This questionnaire study required women to explain,
      in their own words, the meaning of normal and abnormal test results. It was
      discovered that the use of the word cell as a description of findings was
      extremely common, and that a proportion of subjects equated abnormal results with
      technical inadequacy. The frequency of circularity in the interpretations, i.e.
      interpreting 'normal' as 'not abnormal' and vice versa, was striking. Contrary to
      previous research, we find that, whilst many women interpret normal results as
      indicating the current absence of cancer, few appear to believe that future
      cancer is thereby definitively ruled out. By the same token, only a very small
      minority interpret abnormal results as definitive of cancer.

PMID- 15165271
TI  - Significance of atypia in conventional Papanicolaou smears and liquid-based
      cytology: a follow-up study.
AB  - The diagnosis of atypical squamous epithelial cells, borderline nuclear changes,
      is associated with some controversy, as it encompasses benign, reactive, as well
      as possible neoplastic conditions. The aim of this study was to evaluate the
      follow-up diagnoses of cytological atypia in conventional Papanicolaou smears
      (CP) and liquid-based samples by the ThinPrep Pap Test (TP). A total of 1607 CP
      smears from 1 January 2000 to 31 December 2000 and 798 TP samples from 1 January
      2002 to 31 December 2002 diagnosed as atypia were included. The results show that
      the detection rate of atypia in cervical cytological samples was reduced by 41.3%
      (P < 0.001) in TP compared with CP. Cytological and histological follow-up data
      showed the presence of neoplastic lesions in 34.7% of patients screened by TP
      versus 22.3% of patients screened by CP, corresponding to a 55.6% increase in TP
      (P < 0.001). Follow-up diagnosis of mild dysplasia was seen more than twice as
      often in TP than in CP (12.8% versus 5.0%, P < 0.001). The prevalence of moderate
      and severe dysplasia was significantly increased with 26.7% in TP compared with
      CP (21.9% versus 17.2%, P < 0.01). In conclusion, the ThinPrep Pap Test yielded a
      significant decrease in atypia rates compared with the conventional Papanicolaou
      test. In subsequent follow-up the percentage of neoplastic lesions was
      significantly increased in the ThinPrep Pap Test samples.

PMID- 15165272
TI  - MIB-1 immunostaining on cytological samples: a protocol without antigen
      retrieval.
AB  - The aim of the study was to evaluate the effect of fixation procedures on MIB-1
      immunostaining on microwave-treated Papanicolaou-stained slides and to establish
      protocol for MIB-1 immunostaining on cytological samples without microwave pre
      treatment. Cytospins for immunostaining and nuclear suspension for DNA
      measurement were prepared from human breast cancer cell line (MCF-7). Following
      fixation, the cytospins were either stained by Papanicolaou, stored in methanol
      or air-dried. Antigen retrieval by microwave was used before MIB-1 immunostaining
      only for Papanicolaou-stained cytospins. Air-dried cytospins and cytospins stored
      in methanol were immunostained without pre-treatment. The percentage of MIB-1
      positive cells was compared with the S phase fraction of MCF-7 cells calculated
      from DNA histograms. Variations in fixation procedures used before Papanicolaou
      staining had no influence on the percentage of MIB-1 positive cells. The
      difference between the percentage of the MIB-1-positive cells on microwave
      treated Papanicolaou-stained cytospins and on methanol-fixed cytospins without
      microwave pre-treatment was not significant. There was a strong correlation
      between the percentage of the MIB-1-positive cells and S phase fraction.
      Monoclonal antibody MIB-1 recognized Ki-67 antigen in Papanicolaou-stained
      cytospins treated by microwave as well as in cytospins that were fixed and stored
      in methanol without microwave pre-treatment.

PMID- 15165273
TI  - An unusual tumour of the breast: cytological findings.

PMID- 15165274
TI  - Cytopathology in France.
AB  - In France, organization of the cytopathology seems to be quite different from
      that specifically regulated in the USA and in some other European countries. The
      aim of this article is to underline these specificities and to describe the
      solutions we advocate concerning new technologies, teaching, quality assurance,
      national guidelines em leader, to make our current practice compatible with the
      international recommendations. Moreover, we highlight the peculiar status of
      French cytotechnologists' and comment on the recent dramatic decrease of the
      medical demography in France, the consequence of which may promote a controlled
      transfer of competence.

PMID- 15165275
TI  - Malignant pleural effusion of post-transplant neutrophil-rich anaplastic large
      cell lymphoma.

PMID- 15165276
TI  - Comparing conventional and liquid-based smears from a consecutive series of 297
      subjects referred to colposcopy assessment.

PMID- 15165277
TI  - Rapid screening in cervical cytology--a simple method with a big impact.

PMID- 15165278
TI  - Eosinophilic ascites: taxol-induced hypersensitivity?

PMID- 15165281
TI  - The use of ultrasonic reflectoscope for the continuous recording of the movements
      of heart walls. 1954.

PMID- 15165282
TI  - Ultrasound in Lund--three world premieres.

PMID- 15165283
TI  - Early, recent and future applications of echocardiography.

PMID- 15165284
TI  - Tissue Doppler, a fundamental tool for parametric imaging.
AB  - Tissue Doppler has been used for clinical applications since 1989. It has been
      developed from a pulsed Doppler acquisition tool towards a method where
      extraction of velocities can be performed from colour-coded images. This has
      introduced a further development into different forms of parametric images
      describing different myocardial functions as colour-coded information, like
      deformation imaging, motion imaging and phase imaging. The technical requirements
      have been established with temporal requirements of frame rates in acquisition
      exceeding 100 frames s(-1). The most powerful application of the tissue Doppler
      technique today is perhaps to quantify the myocardial functional reserve, during
      stress echocardiography, making the method applicable to diagnose the presence of
      coronary disease with an accuracy exceeding that of nuclear and other non
      invasive techniques. The method has also great potential for future developments
      with introduction of more regional measuring variables.

PMID- 15165285
TI  - Ultrasound augmentation of thrombolysis and tissue perfusion.

PMID- 15165286
TI  - Fetal medicine--a reality thanks to ultrasound.

PMID- 15165287
TI  - Abstracts from the symposium on the occasion of the 50th anniversary of
      echocardiography, Lund, Sweden, 29 October 2003.

PMID- 15165288
TI  - Endothelin receptors as novel targets in tumor therapy.
AB  - The endotelin (ET) axis, that includes ET-1, ET-2, ET-3, and the ET receptors,
      ETA and ETB, plays an important physiological role, as modulator of vasomotor
      tone, tissue differentiation and development, cell proliferation, and hormone
      production. Recently, investigations into the role of the ET axis in mitogenesis,
      apoptosis inhibition, invasiveness, angiogenesis and bone remodeling have
      provided evidence of the importance of the ET-1 axis in cancer. Data suggest that
      ET-1 participates in the growth and progression of a variety of tumors such as
      prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma,
      Kaposi's sarcoma, brain tumors, melanoma, and bone metastases. ET-1 receptor
      antagonists beside providing ideal tools for dissecting the ET axis at molecular
      level have demonstrated their potential in developing novel therapeutic
      opportunity. The major relevance of ETA receptor in tumor development has led to
      an extensive search of highly selective antagonists. Atrasentan, one of such
      antagonists, is orally bioavailable, has suitable pharmacokinetic and toxicity
      profiles for clinical use. Preliminary data from clinical trials investigating
      atrasentan in patients with prostate cancer are encouraging. This large body of
      evidence demonstrates the antitumor activity of endothelin receptor antagonists
      and provides a rationale for the clinical evaluation of these molecules alone and
      in combination with cytotoxic drugs or molecular inhibitors leading to a new
      generation of anticancer therapies targeting endothelin receptors.

PMID- 15165290
TI  - The American Association for Respiratory Care and the National Lung Health
      Education Program: partnering for our patients.

PMID- 15165289
TI  - Evolutionary rate depends on number of protein-protein interactions independently
      of gene expression level.
AB  - BACKGROUND: Whether or not a protein's number of physical interactions with other
      proteins plays a role in determining its rate of evolution has been a contentious
      issue. A recent analysis suggested that the observed correlation between number
      of interactions and evolutionary rate may be due to experimental biases in high
      throughput protein interaction data sets. DISCUSSION: The number of interactions
      per protein, as measured by some protein interaction data sets, shows no
      correlation with evolutionary rate. Other data sets, however, do reveal a
      relationship. Furthermore, even when experimental biases of these data sets are
      taken into account, a real correlation between number of interactions and
      evolutionary rate appears to exist. SUMMARY: A strong and significant correlation
      between a protein's number of interactions and evolutionary rate is apparent for
      interaction data from some studies. The extremely low agreement between different
      protein interaction data sets indicates that interaction data are still of low
      coverage and/or quality. These limitations may explain why some data sets reveal
      no correlation with evolutionary rates.

PMID- 15165291
TI  - The American Association for Respiratory Care and the National Lung Health
      Education Program: assuring quality in spirometry.

PMID- 15165292
TI  - Empowering respiratory therapists to take a more active role in delivering
      quality care for infants with bronchiolitis.
AB  - BACKGROUND: Cincinnati Children's Hospital Medical Center developed a
      bronchiolitis-treatment guideline and implemented a program, led by respiratory
      therapists, to encourage the use of respiratory function assessment to determine
      the need for and effect of bronchodilator treatment of infant bronchiolitis
      patients. METHODS: The program was implemented on January 14, 2002, and included
      (1). a revised respiratory scoring form, (2). a change in the respiratory score
      threshold for a recommendation of bronchodilator treatment, (3). establishment of
      multidisciplinary rounds, (4). providing current data to the respiratory
      therapists, and (5). increasing effective data-based communication between the
      respiratory therapists and physicians. Guideline-eligible patients admitted
      before the implementation of the program (between 12/1/01 and 1/13/02) were
      compared to patients admitted during the program (between 1/14/02 and 3/31/02).
      We compared the mean numbers of bronchodilator treatments per patient in fiscal
      years 2001 and 2002. We defined "perfect respiratory care" as administration of
      bronchodilator only if preceded by suction treatment that resulted in a post
      suction respiratory score >or= 3. RESULTS: Documentation of respiratory scoring
      significantly increased following implementation of the program, as did "perfect
      respiratory care." Between the 2001 and 2002 bronchiolitis seasons, there was a
      decrease in both the mean number and the variability in the number of
      bronchodilator doses administered. CONCLUSIONS: Expanding guideline
      recommendations to the level of specific protocols and empowering respiratory
      therapists to take a more active role improve the quality of care for infant
      bronchiolitis patients.

PMID- 15165293
TI  - Results of a physician and respiratory therapist collaborative effort to improve
      long-term metered-dose inhaler technique in a pediatric asthma clinic.
AB  - BACKGROUND: Despite advances in therapy, asthma continues to be the chronic
      condition most responsible for school absenteeism and pediatric hospitalizations.
      This is especially true for inner-city children. We operate an inner-city
      Pediatric Asthma Compliance and Technique (PACT) clinic in which physicians and
      respiratory therapists collaborate to improve metered-dose inhaler (MDI)
      technique and outcomes among asthmatic children. OBJECTIVE: To determine the
      efficacy of our strategy for improving MDI technique and asthma outcomes.
      METHODS: Children referred to the PACT clinic underwent standardized assessment
      based on the Expert Panel Guidelines of the National Heart, Lung, and Blood
      Institute (NHLBI). Clinicians demonstrated and reinforced correct MDI technique
      at each visit. Using a standardized format we prospectively collected, at the
      patient's first visit (T1) and most recent visit (T2), data on demographics, MDI
      technique scores (MDI steps done correctly; scale of 0-8), pulmonary function,
      and asthma severity (NHLBI classification scale: 1 = mild intermittent to 4 =
      severe persistent). Statistical analyses were performed using parametric and non
      parametric tests. RESULTS: Of the 60 patients who attended the PACT clinic
      between 1999 and 2002, 15 were excluded from the study because of incomplete data
      recording. Mean duration from T1 to T2 was 11.8 +/- 9.5 months. At T1 and T2,
      respectively, the mean MDI-technique scores were 53% and 81%, the mean overall
      asthma severity scores were 2.6 and 2.3, and the mean overall pulmonary function
      severity scores were 2.4 and 2.1. MDI-technique scores significantly improved
      between TI and T2 (p < 0.001). The black patients had the largest improvement in
      MDI technique (p < 0.001), but their pulmonary function test results, overall
      asthma severity, and pulmonary function severity did not improve significantly.
      The white patients significantly improved both their MDI technique (p = 0.004)
      and their overall asthma severity scores (p = 0.005). CONCLUSION: In our PACT
      clinic asthmatic children showed sustained improvement in MDI technique, and some
      of the patients improved in pulmonary function and overall asthma severity score.

PMID- 15165297
TI  - Inhaled bronchodilator administration during mechanical ventilation.
AB  - Inhaled bronchodilators are routinely administered to mechanically ventilated
      patients to relieve dyspnea and reverse bronchoconstriction. A lower percentage
      of the nominal dose reaches the lower respiratory tract in a mechanically
      ventilated patient than in a nonintubated subject, but attention to device
      selection, administration technique, dosing, and patient-ventilator interface can
      increase lower-respiratory-tract deposition in a mechanically ventilated patient.
      Assessing the airway response to bronchodilator by measuring airway resistance
      and intrinsic positive end-expiratory pressure helps guide dosing and timing of
      drug delivery. Selecting the optimal aerosol-generating device for a mechanically
      ventilated patient requires consideration of the ease, reliability, efficacy,
      safety, and cost of administration. With careful attention to administration
      technique, bronchodilator via metered-dose inhaler or nebulizer can be safe and
      effective with mechanically ventilated patients.

PMID- 15165294
TI  - Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab:
      possible zoonotic transmission from a pet cockatiel.
AB  - The use of humanized antibody against tumor necrosis factor alpha (TNF-alpha) may
      increase the risk of various opportunistic infections, including tuberculosis and
      fungal infections. We report a case of cryptococcal pneumonia in a patient who
      was taking infliximab for rheumatoid arthritis. A temporally related exposure
      history raised the possibility that our patient acquired the infection from his
      pet cockatiel. It seems prudent to advise patients receiving infliximab to avoid
      exposure to pet avian excreta.

PMID- 15165296
TI  - Basic techniques for aerosol delivery during mechanical ventilation.
AB  - Among the devices employed for aerosol generation (metered-dose inhalers,
      nebulizers, and dry powder inhalers) only metered-dose inhalers and nebulizers
      are routinely employed for aerosol delivery to mechanically ventilated patients.
      The ventilator circuit and artificial airway were previously thought to be major
      barriers to effective aerosol delivery to mechanically ventilated patients. In
      the past decade in vitro and in vivo investigations have contributed to a better
      understanding of the complex array of factors that influence inhaled drug
      delivery in mechanically-ventilated patients. Several investigators have shown
      that with careful attention to the administration technique aerosol delivery
      efficiency in mechanically-ventilated patients is comparable to that in
      ambulatory patients. The ability to efficiently deliver aerosols should lead to
      wider clinical application of inhaled therapies in patients receiving mechanical
      ventilation.

PMID- 15165298
TI  - Aerosolized antibiotics in mechanically ventilated patients.
AB  - Aerosolized antibiotics are potentially useful in intensive care. At State
      University of New York at Stony Brook we developed a human model of
      tracheobronchitis in intubated patients. The model provides daily specimens of
      airway secretions, allowing serial studies of airway inflammation and testing of
      therapy modes. The presence of local infection is defined by a unique method of
      quantified sputum collection. Bench models have been developed that illustrate
      the factors that limit aerosol delivery to intubated patients. With those models
      clinical trials have defined possible indications for targeted aerosol therapy to
      patients at risk for deep lung infection. An efficient aerosolized-antibiotics
      method that delivers the aerosol past the endotracheal tube has been established,
      and with that method the drug levels in pulmonary secretions exceed by several
      orders of magnitude the levels expected with intravenous therapy. Potential end
      points of therapy are being evaluated, including the rate of bacterial resistance
      and the incidence and definition of deep lung infection.

PMID- 15165299
TI  - Aerosolized prostacyclins.
AB  - Two prostacyclins (prostaglandin E(1) and prostaglandin I(2)) are potent
      vasodilators. Aerosolized prostacyclins reduce pulmonary artery pressure, improve
      right heart function, and increase arterial oxygenation by improving
      ventilation/perfusion matching. This report describes aerosolized prostacyclins
      and compares them to inhaled nitric oxide. I review the types of inhalable
      prostacyclins and their indications, evidence of efficacy, delivery, and adverse
      effects.

PMID- 15165300
TI  - Aerosol delivery to ventilated infant and pediatric patients.
AB  - Infants have low tidal volume, vital capacity, and functional residual capacity,
      and short respiratory cycles (low I:E ratio), which result in a low residence
      time for aerosol particles and, thus, low pulmonary deposition of aerosol
      particles (< 1% of the nominal dose), compared to adults (8-22%). Scintigraphy
      data suggest aerosol deposition of < 1% in both intubated and nonintubated
      infants. In vitro testing appears to overestimate pulmonary deposition, partly
      because in vitro testing does not account for exhaled aerosol. Animal models of
      infant ventilation tend to agree with data from human studies. However, though
      only a small percentage of the aerosol deposits in the lung, infants nevertheless
      receive considerably more aerosolized drug per kilogram of body weight than do
      adults. Efficient aerosol delivery to infants is challenging because of low
      deposition and high inter-patient and intra-patient variability, but existing
      systems can effectively delivery various aerosolized drugs, including
      bronchodilators, anti-inflammatories, and anti-infectives. Use of a nebulizer
      that has a low residual volume (of drug remaining in the device after
      nebulization) delivers up to 13%. Awareness of the variables that impact aerosol
      delivery efficiency can result in more effective treatment of mechanically
      ventilated infants.

PMID- 15165301
TI  - New frontiers in aerosol delivery during mechanical ventilation.
AB  - The scientific basis for inhalation therapy in mechanically-ventilated patients
      is now firmly established. A variety of new devices that deliver drugs to the
      lung with high efficiency could be employed for drug delivery during mechanical
      ventilation. Encapsulation of drugs within liposomes could increase the amount of
      drug delivered, prolong the effect of a dose, and minimize adverse effects. With
      improved inhalation devices and surfactant formulations, inhaled surfactant could
      be employed for several indications in mechanically-ventilated patients. Research
      is unraveling the causes of some disorders that have been poorly understood, and
      our improved understanding of the causal mechanisms of various respiratory
      disorders will provide new applications for inhaled therapies.

PMID- 15165302
TI  - The National Lung Health Education Program: roots, mission, future directions.
AB  - The National Lung Health Education Program (NLHEP), founded in 1997, is a
      national health care initiative to promote early diagnosis of chronic obstructive
      pulmonary disease and related disorders. NLHEP creates and provides lung health
      publications for laypeople and health professionals and develops and conducts
      workshops for health care professionals, to promote clinician expertise in office
      spirometry and spirogram interpretation, and to increase everyone's awareness of
      the effects of smoking and the availability of smoking-cessation programs,
      support systems, and treatments. The American Association for Respiratory Care
      (AARC) has been a NLHEP partner from the beginning, and now those 2 organizations
      are adding another dimension to their partnership: AARC is going to take over all
      NLHEP administrative functions.

PMID- 15165303
TI  - Management dilemmas in laryngeal trauma.
AB  - Laryngeal trauma is an uncommon injury. This has made it difficult for a common
      management pathway to evolve and controversies remain. Methods of airway control,
      usage of investigations and the role of stents or plates in surgical management
      are reviewed. It is important not to delay treatment due to the poor voice and
      airway outcome of chronic laryngeal stenosis.

PMID- 15165304
TI  - Magnetic resonance imaging screening for vestibular schwannoma: analysis of
      published protocols.
AB  - This study seeks to define the most appropriate guidelines for selection of
      patients for magnetic resonance imaging (MRI) to exclude a vestibular schwannoma.
      Improved selection may reduce patient anxiety and improve resource utilization.
      All MRIs of the internal auditory meatus, performed during the year 2000, were
      reviewed. Audiograms and symptoms were collated for all 'positive' scans and 100
      negative scans. Information was analysed using seven published protocols and
      other defined frequency specific criteria. A diagnosis of vestibular schwannoma
      was made on 36 scans. Four criteria had a sensitivity of >95 per cent; of these
      the highest specificity (49 per cent) utilized an interaural difference at two
      adjacent frequencies of 15.dB in unilateral hearing loss and 20.dB in bilateral
      asymmetric loss. Applying our best protocol would have reduced the number of
      scans performed from 392 to 168. The one patient with a vestibular schwannoma who
      was excluded had trigeminal paraesthesia, an independent indication for
      investigation.

PMID- 15165305
TI  - Modified Bondy radical mastoidectomy: long-term personal experience.
AB  - The 'Bondy operation', or modified Bondy radical mastoidectomy, consists of a
      modification of the radical procedure by which the mastoid and epitympanum are
      exteriorized with preservation of the pars tensa and ossicular chain. In the 10
      year period from 1986 to 1996, 53 patients of the ENT Department of the
      University of Pisa underwent a modified Bondy radical mastoidectomy, performed
      with a personalized procedure; 45 of them had a follow up of at least five years.
      After the surgical operation, the ears were free of complications in 38 cases
      (84.5 per cent), while in the other seven cases residual cholesteatoma (one
      case), tympanic retraction (four cases) or recurrent otorrhoea and phlogosis (two
      cases) were observed. The post-operative hearing level was unchanged or improved
      in 41 patients (91 per cent) (33 subjects had an unchanged gap and eight an
      improved gap), and only in the remaining four cases was the gap made worse. Based
      on our experience, the modified Bondy radical mastoidectomy is an extremely
      effective operation with a clear place in modern ENT surgery. When performed on
      carefully selected patients, it has been proven to offer good functional and
      anatomical results.

PMID- 15165306
TI  - Fibroblast growth factor receptor expression in aural polyps: predictor of
      cholesteatoma?
AB  - The cytokine, fibroblast growth factor (FGF) and its receptors (FGFR) have a
      pivotal role in wound repair and have been demonstrated in the perimatrix of
      active cholesteatoma. Aural polyps are a recognized inflammatory reaction of
      middle-ear mucosa to cholesteatoma, but may arise in its absence. This study
      examines 28 archival aural polyp specimens, seeking an increased expression for
      FGFR1 and FGFR3 in polyps associated with cholesteatoma, when compared with those
      arising in non-cholesteatomatous, mucosal disease, but produced a null result.
      There was no difference demonstrated in staining intensity between those polyps
      associated with cholesteatoma and those without. There was a strong correlation
      between staining patterns of FGFR1 and FGFR3 (r = 0.4, p <0.03). The expression
      pattern, of nuclear and perinuclear localization, may support the view that
      nuclear translocation of growth factors, and their receptors, could be related to
      the cellular proliferation that is associated with cholesteatoma.

PMID- 15165307
TI  - Ciliary count in chronic suppurative otitis media: comparative quantitative study
      between mucosal and squamous types using scanning electron microscopy and image
      analysis.
AB  - The objective of this study was to prove ciliary destruction in the middle-ear
      mucous membrane in cases of chronic suppurative otitis media (CSOM) and to
      compare both types of chronic suppurative otitis media with regard to the degree
      of ciliary destruction and ciliary count using objective quantitative techniques.
      The mucosa of the anterior mesotympanum over the promontory was sampled in 10
      patients with mucosal CSOM and in another 10 patients with squamous type CSOM.
      Specimens were examined by scanning electron microscopy in combination with image
      analysis software techniques in order to study the cilia under higher
      magnifications and to calculate the ciliary area. Five patients with
      otosclerosis, no history suggestive of otitis media and normal ear drum
      appearance served as controls. Samples were taken and studied at the Faculty of
      Medicine of Cairo University. CSOM was found to be associated with significant
      ciliary destruction and this was more evident in the squamous type than in the
      mucosal type.

PMID- 15165308
TI  - Prevalence of external auditory canal exostoses in Australian surfboard riders.
AB  - This paper assessed 300 surfboard riders, comprising 229 males and 71 females to
      determine the prevalence and rate of growth of exostoses in this population. A
      group of cold water swimmers and a control group were also examined. Significant
      obstruction, defined as two thirds or more occlusion of the ear canal was noted
      in 90 of the male surfers and 10 female surfers. This degree of occlusion was
      found in seven of the 32 cold water swimmers. A male surfer who has surfed
      regularly for 20 years or more has a one in two chance of developing significant
      obstruction of the external ear canal resulting from exostoses and this is a
      three in seven chance for females.

PMID- 15165309
TI  - Efficacy of endoscopic sinus surgery for paranasal sinus mucocele including
      modified endoscopic Lothrop procedure for frontal sinus mucocele.
AB  - This study evaluated the efficacy of the modified endoscopic Lothrop procedure
      (MELP) for complicated frontal mucoceles and endoscopic marsupialization for
      other paranasal sinus mucoceles. It was a retrospective, consecutive case review
      of sinus mucoceles treated endoscopically by a single surgeon over a four-year
      period (1998-2002). There were 41 mucoceles in 28 patients, including 24 frontal,
      eight frontoethmoidal, three ethmoidal, five maxillary and one frontal mucocele.
      Twenty-one patients underwent the modified Lothrop procedure for frontal
      mucoceles, and seven underwent simple drainage and marsupialization for
      frontoethmoidal, ethmoidal and maxillary mucoceles. At median follow-up of 16
      months, all patients had a patent mucocele opening. Patients treated by drainage
      and marsupialization did not have any complications or mucocele recurrence. All
      patients treated by the modified endoscopic Lothrop procedure had improvement in
      symptoms and signs. Four patients had minor complications including epistaxis and
      adhesions and five required further surgery. The average hospital in-patient stay
      was 2 +/- 1.4 days. Endoscopic techniques, including MELP are effective in the
      short term for the management of complex and simple paranasal sinus mucoceles.
      MELP has a useful place in the management of mucoceles with a significant bony
      partition from an adjacent sinus or nasal cavity. It is also indicated when the
      mucocele is associated with loss of lateral support in the sinus with risk of
      medial-wall collapse of the orbital contents obstructing drainage.

PMID- 15165310
TI  - Implementation by Scottish otolaryngologists of the Scottish Intercollegiate
      Guidelines Network document Management of Sore Throats and the Indications for
      Tonsillectomy: four years on.
AB  - A postal survey was undertaken to assess otolaryngologists' awareness,
      implementation and perceived weaknesses of the Scottish Intercollegiate
      Guidelines Network (SIGN) clinical guideline for the Management of Sore Throat
      and Indications for Tonsillectomy. The reply rate was 77 per cent. There was high
      awareness of the guideline and while 84 per cent of the correspondents felt that
      they followed the guideline, or a guideline based on it, only 35 per cent were
      able to accurately recall the four main criteria recommended for listing for
      tonsillectomy. Twenty-five per cent of the surgeons were in departments that had
      ongoing implementation programmes for these guidelines but only 10 per cent of
      surgeons were in departments that had audited their compliance. The most common
      criticism of the guideline (22 per cent) was that it failed to consider the
      impact of the disease process on the patient's quality of life. Suggestions made
      to improve the guideline are included.

PMID- 15165311
TI  - Role of screening for infectious mononucleosis in patients admitted with
      isolated, unilateral peritonsillar abscess.
AB  - Two hundred and four cases of in-patient admission with isolated, unilateral
      peritonsillar abscess over the three-year period 1999-2001 were reviewed
      retrospectively. One hundred and fifty-one patients had been screened for
      infectious mononucleosis (IM) using the heterophile antibody screening test. Of
      these 142 (94 per cent) tested negative and nine (six per cent) positive. There
      were no IM-typical clinical or haematological signs in any of the IM positive
      patients to facilitate the prediction of the diagnosis. Due to the comparatively
      high prevalence of positives, the low cost of screening, the lack of predictive
      signs and the diversity of potential complications of IM, routine screening in
      all patients presenting with peritonsillar abscess is recommended.

PMID- 15165312
TI  - An innovative approach to anterior rhinoscopy.
AB  - Anterior rhinoscopy with a Thudicum's or Killian's speculum is essential in the
      assessment and treatment of anterior epistaxis. A simple technique for
      visualization of the nasal septum is described which enables a two-handed
      approach to treatment and is achieved with materials readily available in the
      emergency department.

PMID- 15165313
TI  - Cavernous angioma of the internal auditory canal.
AB  - Cavernous angiomas of the internal auditory canal are rare lesions. The authors
      present a case of a 29-year-old lady with multiple infratentorial cavernous
      angiomas, whose sister had previously undergone surgery for a similar
      supratentorial lesion. She initially presented with an acute brainstem haematoma,
      secondary to a pontine cavernous angioma. Three years later she developed
      progressive right-sided sensorineural hearing loss and facial nerve paresis due
      to an internal auditory canal lesion. This was removed via the translabyrinthine
      approach and was found to be a cavernous angioma. This report underlines the
      multiple and dynamic nature of familial cavernous angiomas, as well as the
      importance of follow up to determine whether new symptoms are due to the
      enlargement of known angiomas or the development of new ones. As far as the
      authors are aware, this is the first report describing a cavernous angioma of the
      internal auditory canal in the context of familial and multiple infratentorial
      angiomas.

PMID- 15165315
TI  - Sebaceous carcinoma of the nose: multi-focal presentation?
AB  - Sebaceous carcinoma of the nose is rare. Here the authors present a case of a 71
      year-old man who presented with a mass in the right nasal vestibule. This was
      removed and a nasolabial flap used to reconstruct the defect. Histology revealed
      a sebaceous carcinoma. At follow-up, three months later, a new lesion had
      appeared in the opposite nostril which when removed proved to be a second
      sebaceous carcinoma. This multi-focal presentation in the nose has not been
      described in the literature before.

PMID- 15165314
TI  - Swallowed nasal pack: a rare but serious complication of the management of
      epistaxis.
AB  - Packing of the nose with a suitable material remains a popular method of treating
      epistaxis. The authors report a serious complication of a new design of nasal
      pack; Rapid Rhino, which was swallowed during the treatment of a patient with
      epistaxis, resulting in bowel perforation.

PMID- 15165316
TI  - Infratemporal fossa abscess: complication of maxillary sinusitis.
AB  - This is a case report of a child presenting with a left-sided facial swelling
      with a perimaxillary infratemporal fossa abscess and maxillary sinusitis of the
      same side. The patient was treated by incision and drainage via a sublabial
      approach.

PMID- 15165317
TI  - Fungal laryngitis in immunocompetent patients.
AB  - The diagnosis of fungal laryngitis is often overlooked in systemically
      immunocompetent patients because it is commonly considered a disease of the
      immunocompromised, and because it often mimics, clinically and histologically,
      more common and more serious conditions e.g. leukoplakia. A high index of
      suspicion is required to make the diagnosis, and should be considered in any
      immunocompetent patient with persistent or refractory laryngitis and factors
      predisposing to local mucosal barrier impairment e.g. gastropharyngeal reflux,
      smoking or inhaled steroid use. In such cases, demonstration of hyperkeratosis,
      particularly if associated with intraepithelial neutrophils, on biopsy should
      trigger a search for fungal elements using specialized stains. Prolonged
      treatment by systemic antimycotics is required. Treatment should also include the
      elimination of any predisposing factors, as failure to do so may result in
      difficulty with disease eradication or recurrence of the condition.

PMID- 15165318
TI  - Hyalinizing clear cell carcinoma of the hard palate.
AB  - Hyalinizing clear cell carcinoma (HCCC) of the salivary gland is new disease only
      recognized in recent years. It is rare and the standard treatment is still under
      investigation. This is a report of a 42-year-old female with HCCC who presented
      with a painless submucosal hard palatal mass of three years duration. Wide
      excision of the tumour and the underlying palatal and maxillary bones was
      performed. Pathological examination revealed typical clear cells arranged in
      anastomosing trabeculae, cords, nests, or solid sheets with a hyalinizing stroma.
      These clear cells were positive for the periodic acid-Schiff (PAS) reaction but
      were negative for the mucin stain. Immunohistochemically, these neoplastic cells
      were positive for cytokeratin, but negative for actin. No recurrence nor distant
      metastasis was found during the eight-month follow-up period.

PMID- 15165319
TI  - Mid-line swelling of the palate.
AB  - Sarcoidosis is a multi-system, non-caseating granulomatous disease of unknown
      aetiology that may affect any organ. The oral involvement of sarcoidosis is rare
      and usually an initial manifestation of the disease. In this case report the
      authors present a 25-year-old African-American woman with palatal sarcoidosis
      treated successfully with intra-lesional corticosteroid injections. The oral
      manifestations of sarcoidosis are relatively uncommon and may be the only
      manifestation of the disease. Suspected cases of oral sarcoidosis should be
      biopsied and subsequently referred to a physician to rule out systemic
      involvement.

PMID- 15165321
TI  - Travelling Fellowship 2nd report 2003. Report of visit to USA 29th September-24th
      October 2003.

PMID- 15165320
TI  - Unusual complication of parotid abscess.
AB  - Temporal lobe abscess as a complication of parotid abscess is not described in
      the English literature. In this case report a 66-year-old gentleman is described
      who presented with a left-sided parotid abscess, which extended to other deep
      neck spaces, and advanced to develop a temporal lobe abscess and subdural
      parietal empyema. Treatment included intravenous antibiotics, incision and
      drainage of parotid abscess, and burr hole aspiration of the temporal lobe
      abscess. The importance of imaging to evaluate the extent of deep neck abscess
      and brain abscess is highlighted in this report.

PMID- 15165322
TI  - Prevalence of back and neck pain amongst ENT consultants: national survey.

PMID- 15165323
TI  - Fluorescence fluctuation spectroscopy: a coming of age story.

PMID- 15165324
TI  - Kramers-Kronig relations and sum rules in nonlinear optical spectroscopy.
AB  - The full potential of the Kramers-Kronig relations and sum rules for nonlinear
      susceptibilities has unfortunately drawn relatively little attention in nonlinear
      optical spectra analysis. In this feature article a simple treatment of an
      anharmonic oscillator model in description of the nonlinear susceptibility of
      media and holomorphic properties of the nonlinear susceptibility were utilized.
      Using such concepts, conventional Kramers-Kronig, multiply-subtractive Kramers
      Kronig, and generalized Kramers-Kronig dispersion relations can be derived. We
      demonstrate how in practice the variety of different Kramers-Kronig relations
      mentioned above, as well as various sum rules, can be applied in nonlinear
      optical spectra analysis. As an example we treat the third-harmonic wave
      generation spectrum from a polymer.

PMID- 15165325
TI  - Thermal signature characteristics of vehicle/terrain interaction disturbances:
      implications for battlefield vehicle classification.
AB  - Thermal emissivity spectra (8-14 microm) of track impressions/background were
      determined in conjunction with operation of six military vehicle types, T-72 and
      M1 Tanks, an M2 Bradley Fighting Vehicle, a 5-ton truck, a D7 tractor, and a High
      Mobility Multipurpose Wheeled Vehicle (HMMWV), over diverse soil surfaces to
      determine if vehicle type could be related to track thermal signatures. Results
      suggest soil compaction and fragmentation/pulverization are primary parameters
      affecting track signatures and that soil and vehicle/terrain-contact type
      determine which parameter dominates. Steel-tracked vehicles exert relatively low
      ground-contact pressure but tend to fragment/pulverize soil more so than do
      rubber-tired vehicles, which tend mainly to compact. In quartz-rich, lean clay
      soil tracked vehicles produced impressions with spectral contrast of the quartz
      reststrahlen features decreased from that of the background. At the same time, 5
      ton truck tracks exhibited increased contrast on the same surface, suggesting
      that steel tracks fragmented soil while rubber tires mainly produced compaction.
      The structure of materials such as sand and moist clay-rich river sediment makes
      them less subject to further fragmentation/pulverization; thus, compaction was
      the main factor affecting signatures in these media, and both tracked and wheeled
      vehicles created impressions with increased spectral contrast on these surfaces.
      These results suggest that remotely sensed thermal signatures could differentiate
      tracked and wheeled vehicles on terrain in many areas of the world of strategic
      interest. Significant applications include distinguishing visually/spectrally
      identical lightweight decoys from actual threat vehicles.

PMID- 15165327
TI  - Infrared spectroscopy of OD vibrators in minerals at natural dilution: hydroxyl
      groups in talc and kaolinite, and structural water in beryl and emerald.
AB  - An infrared (IR) study of natural deuteration is conducted on minerals containing
      hydroxyl groups (talc and kaolinite) and channel-water-bearing minerals (beryl
      and emerald). In talc, the OD valence vibration is located at 2710 cm(-1),
      corresponding to OD groups surrounded by 3 Mg atoms. In kaolinite, the OD valence
      vibrations are located at 2671 cm(-1) (inner OD group), 2712, 2706, and 2700 cm(
      1) (three inner-surface OD groups). In beryl and emerald, natural deuteration of
      channel water is observed for the first time by infrared microspectroscopy. In
      beryl from Minas Gerais (Brazil), the OD profiles are characterized by four bands
      at 2735, 2686, 2672, and 2641 cm(-1). In emeralds from Colombia and Brazil, the
      OD profiles are characterized by five or four bands, respectively, at 2816, 2737,
      2685, 2673, and 2641 cm(-1) (Colombia) and 2730, 2684, 2672, and 2640 cm(-1)
      (Brazil). The band at 2816 cm(-1) can be assigned to -OD or OD(-), and bands at
      2686-2684, 2673-2672, and 2641-2640 cm(-1) can be assigned to type-I and type-II
      HOD molecules. The band at 2737-2730 cm(-1) is partially disturbed by combination
      bands of the mineral. Such OD profiles are different from those obtained by
      artificial deuteration at higher OD dilution.

PMID- 15165326
TI  - Fourier transform infrared-attenuated total reflection nitrate determination of
      soil pastes using principal component regression, partial least squares, and
      cross-correlation.
AB  - This paper investigates the use of Fourier transform infrared (FTIR) attenuated
      total reflectance (ATR) spectroscopy as a fast and simple way for direct
      determination of nitrate concentration in soil pastes, which would assist
      precision fertilizer placement and reduce nitrate pollution. Eight types of soils
      are investigated, with nitrate concentrations ranging from 0 to 1000 ppm-N. The
      spectral region around the nitrate band (1300-1550 cm(-1)) is analyzed by (1)
      principal component regression (PCR), (2) partial least squares (PLS), and (3)
      cross-correlation with reference libraries that include spectra of pure ions
      and/or soils. The main obstacle to accurate nitrate measurement appears to be an
      interfering band present in calcareous soils. This band, which may be due to
      carbonate, is located around 1450 cm(-1) and overlaps with the nitrate band
      centered around 1370 cm(-1). For non-calcareous soils, and in particular for
      light sandy agricultural soils, PLS and cross-correlation with a reference
      library containing only spectra of ions in water give similar results (about 8
      ppm-N on dry soil basis), while PCR leads to slightly poorer results. When
      calcareous soils are included in the analysis, the prediction errors are about
      twice as large. In this case, the best results are obtained using PLS, followed
      by PCR, while cross-correlation with reference libraries leads to poorer results.

PMID- 15165328
TI  - Water-related matrix isolation phenomena during NO2 photolysis in argon matrix.
AB  - Photolysis (350-450 nm) of NO(2) molecules trapped in argon matrices at 10 K has
      been studied using Fourier transform infrared (FTIR) spectroscopy to examine the
      mobility of the photolysis products, O((3)P) and NO, and their subsequent
      reactions. The formation of N(2)O(5) and N(2)O(3) from reactions of these mobile
      species with immobilized NO(2) and N(2)O(4) is confirmed. Water molecules from
      the background gases in the vacuum have been found to be isolated in the argon
      matrix during deposition of diluted NO(2) in Ar. The entrapped water molecules
      along with some of their NO(2) adducts have been characterized. Exposure of the
      matrix to photons to photolyze NO() resulted in not only internal matrix
      reactions, but also an enhanced deposition of ice over the surface of the argon
      matrix. This is caused by photodesorption of water molecules from the walls of
      the matrix isolation chamber and their subsequent condensation on the matrix
      surface. This ice overlayer has been found to give a very significant dangling OH
      band and a substantial librational band in the FT-IR spectra, indicating
      substantial surface area and internal porosity, respectively. The potential of
      using photodesorbed water to establish high surface area ice interfaces with
      dangling OH groups for heterogeneous photoreaction studies is discussed.

PMID- 15165329
TI  - Fourier transform infrared studies on deblocking and crosslinking mechanisms of
      some fluorine containing monocomponent polyurethanes.
AB  - The thermal reactivity of a set of different blocked perfluoropolyether (PFPE)
      containing polyisocyanates and one monocomponent polyurethane containing a PFPE
      diol was investigated by Fourier transform infrared (FT-IR) spectroscopy. With
      the former series of products the deblocking kinetics at 90 degrees C and 120
      degrees C were investigated with time-dependent spectral data, showing the
      highest thermal deblocking activity for 3,5 dimethylpyrazole blocking agent. The
      crosslinking reaction of the PFPE diol with ketoxime blocked isocyanurate at 150
      degrees C was monitored by infrared (IR) spectroscopy and two-dimensional (2D)
      correlation analysis; the results suggested a prevailing direct condensation
      mechanism and the formation of urea byproducts in the later stages of reaction.
      Both synchronous and asynchronous spectra were considered and discussed, pointing
      out the time relation of the chemical functions during the crosslinking
      experiment.

PMID- 15165330
TI  - Quantitative analysis of the in situ Fourier transform infrared absorption and
      emission spectrum of gas-phase SiO (Deltav = 1 and 2) produced in Si-N-O fiber
      growth.
AB  - The in situ Fourier transform infrared (FT-IR) spectrum of gasphase SiO produced
      in silicon oxynitride fiber growth has been quantitatively analyzed. Both
      absorption and emission FT-IR spectra at a spectral resolution of 0.5 cm(-1) were
      produced from the reaction zone at 1450 degrees C. The fundamental and hot bands
      were observed with vibrational levels up to v = 7. For the purposes of
      quantitative analysis the individual vibration-rotation integrated line strengths
      for the three main isotopes,( 28)SiO,( 29)SiO, and( 30)SiO, were calculated based
      on ab initio quantum chemical calculations of the electric dipole moment function
      and the transition moment. Vibrational anharmonicity and Hermann-Wallis
      correction factors were also incorporated. From the line strengths at specific
      temperatures and the known Dunham coefficients, the absorbance spectrum was
      simulated with best fits giving the averaged SiO concentration in the 400 mm
      reaction zone of 1.0 x 10(17) molecules/cm(3). Such quantitative measurements
      demonstrate the power of in situ infrared (IR) spectroscopy combined with quantum
      chemical calculations. The rapid determination of synthetic calibration datasets
      for chemometric analysis can thus lead to correlation of gas-phase species
      concentrations with fiber growth properties and subsequently to real-time process
      control.

PMID- 15165331
TI  - Photoacoustic distributed feedback laser spectroscopy on hydrogen fluoride.
AB  - We have developed a photoacoustic spectrometer based on a distributed feedback
      (DFB) diode laser. The single-mode emission of the laser can be tuned
      continuously over 700 GHz enabling the precise determination of absorption line
      parameters. Our experiments were performed on the rotational lines P2 and P3 of
      the vibrational transition 2-0 (overtone) of hydrogen fluoride (HF) at 1304.534
      nm and 1312.591 nm (vacuum), respectively. The pressure broadening coefficient
      due to elastic collisions with N(2) molecules is found to be 5.92 +/- 0.04
      GHz/atm (296 K) and 5.38 +/- 0.04 GHz/atm, respectively. The Doppler linewidths
      turn out to be 630 +/- 40 MHz and 670 +/- 40 MHz (296 K), respectively. The
      pressure-induced line shifts of the absorption lines for N(2) are 540 +/- 40 MHz/
      atm and 580 +/- 40 MHz/atm, respectively.

PMID- 15165332
TI  - Vibrational spectra and surface-enhanced vibrational spectra of 1-nitropyrene.
AB  - The present report on the vibrational spectra of 1-nitropyrene (1NP) describes
      the infrared and Raman spectra; their interpretation is aided by local density
      functional theory (DFT) calculations at the B3LYP/6-311G(d, p) level of theory
      and by the surface-enhanced vibrational spectra (SEVS) with the final objective
      of trace organic analytical applications. The surface-enhanced Raman scattering
      (SERS) on silver island films and mixed silver/gold island films was investigated
      with several laser lines in the visible region. Surface-enhanced infrared
      absorption (SEIRA) was attempted on silver and gold island films. The interface
      of the organic 1-NP with smooth metal surfaces of silver and copper was also
      probed using reflection-absorption infrared (RAIRS) spectra that, in conjunction
      with the transmission spectra, allow one to extract the molecular orientation in
      vacuum evaporated thin solid films. Chemical adsorption of 1-NP on silver and
      further photochemical decomposition of the 1-NP-metal adsorbates was detected
      with all visible laser lines. Resonance Raman scattering (RRS) using UV-laser
      excitation at 325 nm was also recorded.

PMID- 15165333
TI  - Adsorption of a cholesteric liquid crystal polyester on silver nanoparticles
      studied by surface-enhanced Raman scattering and micro Raman spectroscopy.
AB  - A Raman study of the adsorption of thermotropic cholesteric liquid crystal
      polyester PTOBDME ([C(34)H(36)O(8)](n)) on Ag surfaces is presented in this work.
      The affinity and adsorption mechanism of this polymer was tested on Ag metal
      colloids and on Ag films obtained by direct immobilization of the colloidal
      nanoparticles. We have first studied the structure of PTOBDME suspended in
      several solvents in order to identify the Raman bands used as structural markers.
      The adsorption of the polymer leads to a deep conformational change involving
      both the main chain and the aliphatic side chain. The interaction of polymers
      like PTOBDME with metals could be interesting in the formation of functionalized
      surfaces, providing them with specific physicochemical properties with possible
      applications in recognition phenomena, which can be easily characterized by Raman
      spectroscopy.

PMID- 15165334
TI  - Part I: surface-enhanced Raman spectroscopy investigation of amino acids and
      their homodipeptides adsorbed on colloidal silver.
AB  - Surface-enhanced Raman scattering spectra (SERS) were measured for various amino
      acids: L-methionine (Met), L-cysteine (Cys), Lglycine (Gly), L-leucine (Leu), L
      phenylalanine (Phe), and L-proline (Pro) and their homodipeptides (Met-Met, Cys
      Cys, Gly-Gly, LeuLeu, Phe-Phe, and Pro-Pro) in silver colloidal solutions. The
      geometry and orientation of the amino acids or dipeptides on the silver surface,
      and their specific interaction with the surface, were deducted by detailed
      spectral analysis of the SERS spectra. This analysis has allowed us to propose
      the particular surface geometry of amino acids or dipeptides and also implied
      that C-C bonds were almost parallel to the surface, as evidenced by the absence
      of marker bands in the skeletal C-C stretching region of the spectra.
      Additionally, using "time-dependent" SERS measurements we solved an existing
      controversy regarding the binding specificity of Gly-Gly on the silver surface.

PMID- 15165335
TI  - Part II: surface-enhanced Raman spectroscopy investigation of methionine
      containing heterodipeptides adsorbed on colloidal silver.
AB  - Surface-enhanced Raman scattering (SERS) spectra of methionine (Met) containing
      dipeptides: Met-X and X-Met, where X is: L-glycine (Gly), L-leucine (Leu), L
      proline (Pro), and L-phenylalanine (Phe) are reported. Using pre-aggregated Ag
      colloid we obtained high-quality SERS spectra of these compounds spontaneously
      adsorbed on colloidal silver. Additionally, we measured Raman spectra (RS) of
      these heterodipeptides in a solid state as well as in acidic and basic solutions.
      The RS and SERS spectra of Met-X and X-Met presented in this work appear to be
      different. One of the most prominent and common features in the SERS spectra of
      all these dipeptides is a band in the 660-690 cm(-1) range that is due to the C-S
      stretching, v(CS), vibration of Met. This suggests that all the abovementioned
      compounds adsorb on the silver surface through a thioether atom. On the other
      hand, the SERS spectra of X-Met show clearly that not only the S atom but also
      the carboxylate group interact with the colloid surface as manifested by the
      enhancement of bands in the 920-930 and 1380-1396 cm(-1) regions. These bands are
      ascribed to the v(C-COO(-)) and v(sym)(COO(-)) vibrations, respectively.
      Additionally, a SERS spectrum of Phe-Met indicates that the interaction of the
      thioether atom, amine group, and aromatic side chain with the silver surface is
      favorable and may dictate the orientation and conformation of adsorbed peptide.

PMID- 15165336
TI  - Photon migration in Raman spectroscopy.
AB  - Monte Carlo simulation has been applied to study time-resolved Raman and Tyndall
      photon migration in opaque samples under isotropic and forward scattering
      conditions. For isotropic scattering, Raman and Tyndall intensities are predicted
      to decay according to t((1-n)) and t(-n), respectively, where the value of n
      depends on the ratio of the optical collection aperture to the mean scattering
      length. The simulation correctly reproduced the analytical results of n = 3/2 and
      n = 5/2 for a point source in infinite and semi-infinite media, respectively. In
      addition the model can be used to relate the time at which a Raman photon exits
      the sample to the mean depth at which it was generated. This could provide a
      useful tool for depth profiling the chemical composition of turbid systems, and
      hence be a useful addition to the established array of photon-migration
      techniques. The model was applied to analyze experimentally observed Raman and
      Tyndall decay profiles from powdered trans-stilbene. The transport mean free path
      (l(t)) was calculated to be approximately 400 microm, which was significantly
      larger than the particle sizes present in the sample (approximately 10-100
      microm). This implies that the particles were highly forward scattering, as would
      be expected for this size range. When highly anisotropic scattering was
      introduced into the model a much more reasonable scattering length (l(s)
      approximately 40 microm) was obtained. Finally, a simple analytical model was
      developed that gives the correct relationship between the Raman and Tyndall decay
      exponents for isotropic scattering. To the best of our knowledge this work
      represents the first detailed study of Raman photon migration under time-resolved
      conditions.

PMID- 15165337
TI  - Characterization of the structures of size-selected TiO2 nanoparticles using X
      ray absorption spectroscopy.
AB  - To investigate the relationship between the size and structure of TiO(2)
      nanoparticles, three size-selected samples of TiO(2) nanoparticles were prepared
      via a hydrolysis method that uses Ti[OCH(CH(3))(2)](4) as the starting material.
      The structures of the nanoparticles were characterized using powder X-ray
      diffraction (XRD), transmission electron microscopy (TEM), and X-ray absorption
      spectroscopy (XAS). Analysis of the XRD patterns and of the TEM images showed
      that the samples were dispersed, with an average particle size of approximately
      30 nm (sample A), approximately 12 nm (sample B), and approximately 7 nm (sample
      C). Their X-ray absorption spectra indicate that samples A and B have an anatase
      structure, whereas sample C has a structure very similar to that of the TiO( 2)
      II phase, which generally arises only under high-pressure conditions. This
      difference can be attributed to size-induced radial pressure within the smaller
      nanoparticles, which plays an important role in the phase of TiO(2) nanoparticles
      in sample C.

PMID- 15165338
TI  - Comparison of methods for rapid evaluation of lifetimes of exponential decays.
AB  - For evaluating exponential luminescence decays, there are a variety of
      computational rapid integral methods based on the areas of the decay under
      different binned intervals. Using both Monte Carlo methods and experimental
      photon counting data, we compare the standard rapid lifetime determination method
      (SRLD), optimized rapid lifetime determination methods (ORLD), maximum likelihood
      estimator method (MLE), and the phase plane method (PPM). The different
      techniques are compared with respect to precision, accuracy, sensitivity to
      binning range, and the effect of baseline interference. The MLE provides the best
      overall precision, but requires 10 bins and is sensitive to very small
      uncorrected baselines. The ORLD provides nearly as good precision using only two
      bins and is much more immune to uncompensated baselines. The PPM requires more
      bins than the MLE and has systematic errors, but is largely resistant to baseline
      issues. Therefore, depending on the data acquisition method and the number of
      bins that can be readily employed, the ORLD and MLE are the preferred methods for
      reasonable signal-to-noise ratios.

PMID- 15165339
TI  - Further investigations on a poly(vinyl alcohol)- polyelectrolyte chemically
      selective optical film.
AB  - The ionomer poly(vinylbenzyltrimethylammonium chloride) has been blended with
      cross-linked poly(vinyl alcohol) to form optically clear composites that can be
      covalently linked as thin films to oxide surfaces. Films are characterized using
      spectroscopic ellipsometry with refractive index (n) and extinction coefficient
      (k) data presented for wavelengths 300 to 1100 nm. A refractive index of 1.54 and
      average thickness of 709 nm are typical of an air dry film prepared by spin
      coating. Dynamic in situ ellipsometry results for films exposed to 0.1 M KNO(3)
      and 1.0 mM Fe(CN)(6)(-3) are presented. Upon initial exposure to 0.1 M KNO(3), an
      air dry film expands by about 160% and stabilizes in size and refractive index at
      about 18 hours. Ion exchange of film cationic groups with ferricyanide is marked
      by slight film contraction, presumably due to electrostatic cross-linking by the
      multivalent anion. These films are useful in the spectroelectrochemical sensor
      with our newly developed fluorescence detection mode, as demonstrated by results
      of the reversible incorporation of the fluorescent anion fluorescein.

PMID- 15165340
TI  - Time-resolved fluorescence spectroscopic study of crude petroleum oils: influence
      of chemical composition.
AB  - The fluorescence of crude petroleum oils is sensitive to changes in chemical
      composition and many different fluorescence methods have been used to
      characterize crude oils. The use of fluorescence lifetimes to quantitatively
      characterize oil composition has practical advantages over steady-state
      measurements, but there have been comparatively few studies in which the lifetime
      behavior is correlated with gross chemical compositional data. In this study, the
      fluorescence lifetimes for a series of 23 crude petroleum oils with American
      Petroleum Institute (API) gravities of between 10 and 50 were measured at several
      emission wavelengths (450-785 nm) using a 380 nm light emitting diode (LED)
      excitation source. It was found that the intensity average fluorescence lifetime
      (tau) at any emission wave-length does not correlate well with either API gravity
      or aromatic concentration. However, it was found that tau is strongly negatively
      correlated with both the polar and sulfur concentrations and positively
      correlated with the corrected alkane concentration. This indicates that the
      fluorescence behavior of crude petroleum oils is governed primarily by the
      concentration of quenching species. All the strong lifetime-concentration
      correlations are nonlinear and show a high degree of scatter, especially for
      medium to light oils with API gravities of between 25 and 40. The degree of
      scatter is greatest for oils where the concentrations (wt %) of the polar
      fraction is approximately 10 +/- 4%, the asphaltene component is approximately 1
      +/- 0.5%, and sulfur is 0.5 +/- 0.4%. This large degree of scatter precludes the
      use of average fluorescence lifetime data obtained with 380 nm excitation for the
      accurate prediction of the common chemical compositional parameters of crude
      petroleum oils.

PMID- 15165341
TI  - Influence of wavelength-shifted calibration spectra on multivariate calibration
      models.
AB  - Multivariate calibration models are sensitive to wavelength shifts in calibration
      spectra as such disturbances are linearly independent from unshifted spectra and
      increase the calibration model's dimension. However, if wavelength shifts
      included in the calibration model are random, the predictability of the model is
      not improved. On the contrary, overfitting is introduced, thereby increasing the
      prediction error. Because calibration spectra are defined to be error free and
      are the only available data at that point, there is no analytical way to find out
      that the calibration model is erroneous. This study gives a mathematical
      explanation of how the model's dimension is increased by wavelength shifts and
      that the additional basis vectors, principal components for instance, possess
      derivative-shaped features. It is also demonstrated by means of an example that
      the reverse is not necessarily true. Hence, derivative-shaped features found in
      principal components are no indication of wavelength-shifted calibration spectra.
      A method is presented for analyzing calibration spectra for such shifts. The
      algorithm takes advantage of the fact that artificial shift compensations of true
      shifts increase the similarity, i.e., correlation, of shifted spectra with
      respect to the remaining, unshifted spectra. Synthetic and experimental data are
      used to demonstrate and assess the performance of the algorithm. It is shown that
      wavelength shifts in calibration spectra can be detected and corrected if a small
      number of spectra are disturbed. Significant improvements of the prediction
      errors of chemometric calibration models can be achieved by means of this shift
      correction algorithm.

PMID- 15165342
TI  - Application of deep blue diode laser to resonance Raman spectroscopy of
      hemoproteins.

PMID- 15165343
TI  - Parietal lobe lesions disrupt saccadic remapping of inhibitory location tagging.
AB  - Maintaining a coherent percept of the visual scene while eye position
      continuously changes requires that saccades be accompanied by remapping of the
      visual environment. We studied saccadic remapping in patients with unilateral
      lesions in the intraparietal sulcus and healthy controls, using inhibition of
      return (IOR)-an inhibitory tag that enables efficient visual search. In healthy
      controls, IOR was found at both retinal and environmental locations of the cue,
      indicating that the inhibitory tag had been remapped into environmental
      coordinates. In contrast, right parietal patients demonstrated IOR only at the
      retinal location of the cue, indicating that the intraparietal sulcus is involved
      in remapping of the environment after eye movements to afford a stable,
      environmentally based reference frame. Note that patients did not show
      environmental IOR in either visual field. These results also suggest that this
      region may be the neural substrate for encoding inhibitory spatial tags in an
      environmentally based reference frame.

PMID- 15165344
TI  - Path integration deficits during linear locomotion after human medial temporal
      lobectomy.
AB  - Animal navigation studies have implicated structures in and around the
      hippocampal formation as crucial in performing path integration (a method of
      determining one's position by monitoring internally generated self-motion
      signals). Less is known about the role of these structures for human path
      integration. We tested path integration in patients who had undergone left or
      right medial temporal lobectomy as therapy for epilepsy. This procedure removed
      approximately 50% of the anterior portion of the hippocampus, as well as the
      amygdala and lateral temporal lobe. Participants attempted to walk without vision
      to a previously viewed target 2-6 m distant. Patients with right, but not left,
      hemisphere lesions exhibited both a decrease in the consistency of path
      integration and a systematic underregistration of linear displacement (and/or
      velocity) during walking. Moreover, the deficits were observable even when there
      were virtually no angular acceleration vestibular signals. The results suggest
      that structures in the medial temporal lobe participate in human path integration
      when individuals walk along linear paths and that this is so to a greater extent
      in right hemisphere structures than left. This information is relevant for future
      research investigating the neural substrates of navigation, not only in humans
      (e.g., functional neuroimaging and neuropsychological studies), but also in
      rodents and other animals.

PMID- 15165345
TI  - Direct current stimulation over V5 enhances visuomotor coordination by improving
      motion perception in humans.
AB  - The primary aim of this study was to determine the extent to which human MT+/V5,
      an extrastriate visual area known to mediate motion processing, is involved in
      visuomotor coordination. To pursue this we increased or decreased the
      excitability of MT+/V5, primary motor, and primary visual cortex by the
      application of 7 min of anodal and cathodal transcranial direct current
      stimulation (tDCS) in healthy human subjects while they were performing a
      visuomotor tracking task involving hand movements. The percentage of correct
      tracking movements increased specifically during and immediately after cathodal
      stimulation, which decreases cortical excitability, only when V5 was stimulated.
      None of the other stimulation conditions affected visuomotor performance. We
      propose that the improvement in performance caused by cathodal tDCS of V5 is due
      to a focusing effect on to the complex motion perception conditions involved in
      this task. This hypothesis was proven by additional experiments: Testing simple
      and complex motion perception in dot kinetograms, we found that a diminution in
      excitability induced by cathodal stimulation improved the subject's perception of
      the direction of the coherent motion only if this was presented among random dots
      (complex motion perception), and worsened it if only one motion direction was
      presented (simple movement perception). Our data suggest that area V5 is
      critically involved in complex motion perception and identification processes
      important for visuomotor coordination. The results also raise the possibility of
      the usefulness of tDCS in rehabilitation strategies for neurological patients
      with visuomotor disorders.

PMID- 15165346
TI  - Two visual motion processing deficits in developmental dyslexia associated with
      different reading skills deficits.
AB  - Developmental dyslexia is associated with deficits in the processing of visual
      motion stimuli, and some evidence suggests that these motion processing deficits
      are related to various reading subskills deficits. However, little is known about
      the mechanisms underlying such associations. This study lays a richer groundwork
      for exploration of such mechanisms by more comprehensively and rigorously
      characterizing the relationship between motion processing deficits and reading
      subskills deficits. Thirty-six adult participants, 19 of whom had a history of
      developmental dyslexia, completed a battery of visual, cognitive, and reading
      tests. This battery combined motion processing and reading subskills measures
      used across previous studies and added carefully matched visual processing
      control tasks. Results suggest that there are in fact two distinct motion
      processing deficits in developmental dyslexia, rather than one as assumed by
      previous research, and that each of these deficits is associated with a different
      type of reading subskills deficit. A deficit in detecting coherent motion is
      selectively associated with low accuracy on reading subskills tests, and a
      deficit in discriminating velocities is selectively associated with slow
      performance on these same tests. In addition, evidence from visual processing
      control tasks as well as self-reports of ADHD symptoms suggests that these motion
      processing deficits are specific to the domain of visual motion, and result
      neither from a broader visual deficit, nor from the sort of generalized attention
      deficit commonly comorbid with developmental dyslexia. Finally, dissociation
      between these two motion processing deficits suggests that they may have distinct
      neural and functional underpinnings. The two distinct patterns of motion
      processing and reading deficits demonstrated by this study may reflect separable
      underlying neurocognitive mechanisms of developmental dyslexia.

PMID- 15165348
TI  - ERP effects of subject-verb agreement violations in patients with Broca's
      aphasia.
AB  - This article presents electrophysiological data on on-line syntactic processing
      during auditory sentence comprehension in patients with Broca's aphasia. Event
      related brain potentials (ERPs) were recorded from the scalp while subjects
      listened to sentences that were either syntactically correct or contained
      violations of subject-verb agreement. Three groups of subjects were tested: Broca
      patients (n = 10), nonaphasic patients with a right-hemisphere (RH) lesion (n =
      5), and healthy aged-matched controls (n = 12). The healthy, control subjects
      showed a P600/SPS effect as response to the agreement violations. The nonaphasic
      patients with an RH lesion showed essentially the same pattern. The overall group
      of Broca patients did not show this sensitivity. However, the sensitivity was
      modulated by the severity of the syntactic comprehension impairment. The largest
      deviation from the standard P600/SPS effect was found in the patients with the
      relatively more severe syntactic comprehension impairment. In addition, ERPs to
      tones in a classical tone oddball paradigm were also recorded. Similar to the
      normal control subjects and RH patients, the group of Broca patients showed a
      P300 effect in the tone oddball condition. This indicates that aphasia in itself
      does not lead to a general reduction in all cognitive ERP effects. It was
      concluded that deviations from the standard P600/SPS effect in the Broca patients
      reflected difficulties with on-line maintaining of number information across
      clausal boundaries for establishing subject-verb agreement.

PMID- 15165347
TI  - ERPs reflect lexical identification in word fragment priming.
AB  - Behavioral evidence suggests that spoken word recognition involves the temporary
      activation of multiple entries in a listener's mental lexicon. This phenomenon
      can be demonstrated in cross-modal word fragment priming (CMWP). In CMWP, an
      auditory word fragment (prime) is immediately followed by a visual word or
      pseudoword (target). Experiment 1 investigated ERPs for targets presented in this
      paradigm. Half of the targets were congruent with the prime (e.g., in the prime
      target pair: AM-AMBOSS [anvil]), half were not (e.g., AM-PENSUM [pensum]).
      Lexical entries of the congruent targets should receive activation from the
      prime. Thus, lexical identification of these targets should be facilitated. An
      ERP effect named P350, two frontal negative ERP deflections, and the N400 were
      sensitive to prime-target congruency. In Experiment 2, the relation of the
      formerly observed ERP effects to processes in a modality-independent mental
      lexicon was investigated by presenting primes visually. Only the P350 effect
      could be replicated across different fragment lengths. Therefore, the P350 is
      discussed as a correlate of lexical identification in a modality-independent
      mental lexicon.

PMID- 15165349
TI  - Probing the prerequisites for motion blindness.
AB  - Neurobiological studies of visual awareness usually focus on the neural events
      elicited by perceived or nonperceived stimuli but neglect the preexisting
      conditions that allow (or prevent) conscious perception. We have examined the
      conditions that lead to temporary motion blindness in a rapid serial visual
      presentation paradigm, in which subjects have to detect coherent motion in the
      peripheral stream after a cue (a red fixation point) in the central stream. The
      failure of awareness depends critically on the occurrence of similar coherent
      motion events (probes) before the cue. Event-related brain potentials (ERPs) were
      recorded to track the processing of motion distractors, which determine the
      prerequisites for this transient deficit. Analysis of motion-evoked responses
      revealed that there is no progressive reduction in sensitivity in early visual
      processing. There is, however, a progressive increase in amplitude of a negative
      wave over the frontal cortex at approximately 250 msec after motion onset and a
      corresponding reduction of a centro-parietal positivity at approximately 350 msec
      with an increasing number of distractors. We propose that these nonsensory ERP
      components reflect a postperceptual frontal gating mechanism that controls the
      access of visual stimuli to higher order evaluation and conscious detection.

PMID- 15165350
TI  - Event-related brain potentials elicited by morphological, homographic,
      orthographic, and semantic priming.
AB  - The morphological structure of words, in terms of their stem morphemes and
      affixes, could influence word access and representation in lexical memory. Three
      experiments were carried out to explore the attributes of event-related
      potentials evoked by different types of priming. Morphological priming, with
      pairs of words related by their stem (hijo/hija [ son/ daughter]), produced a
      sustained attenuation (and even a tendency to positivity) of the N400 shown by
      unrelated words across the three experiments. Homographic priming (Experiment 1),
      using pairs of words with a superficially similar stem, but without morphological
      or semantic relation (foco/foca [floodlight/seal]), produced an initial
      attenuation similar to the morphological pairs, but which rapidly tended to form
      a delayed N400, due to the impossibility of integration. However, orthographic
      priming (rasa/rana [flat/frog]) in Experiment 2 does not produce attenuation of
      the N400 but an effect similar to that of unrelated pairs. Experiment 3 shows
      that synonyms advance more slowly than morphological pairs to meaning coherence,
      but finally produce a more positive peak around 600 msec.

PMID- 15165351
TI  - Decomposing components of task preparation with functional magnetic resonance
      imaging.
AB  - It is widely acknowledged that the prefrontal cortex plays a major role in
      cognitive control processes. One important experimental paradigm for
      investigating such higher order cognitive control is the task-switching paradigm.
      This paradigm investigates the ability to switch flexibly between different task
      situations. In this context, it has been found that participants are able to
      anticipatorily prepare an upcoming task. This ability has been assumed to reflect
      endogenous cognitive control. However, it is difficult to isolate task
      preparation process from task execution using functional magnetic resonance
      imaging (fMRI). In the present study, we introduce a new experimental
      manipulation to investigate task preparation with fMRI. By manipulating the
      number of times a task was prepared, we could demonstrate that the left inferior
      frontal junction (IFJ) area (near the junction of inferior frontal sulcus and
      inferior precentral sulcus), the right inferior frontal gyrus, and the right
      intraparietal sulcus are involved in task preparation. By manipulating the cue
      task mapping, we could further show that this activation is not related to cue
      encoding but to the updating of the relevant task representation. Based on these
      and previous results, we assume that the IFJ area constitutes a functionally
      separable division of the lateral prefrontal cortex. Finally, our data suggest
      that task preparation does not differ for switch and repetition trials in
      paradigms with a high proportion of switch trials, casting doubt on the
      assumption that an independent task set reconfiguration process takes place in
      the preparation interval.

PMID- 15165352
TI  - Motor sequence complexity and performing hand produce differential patterns of
      hemispheric lateralization.
AB  - Studies in brain damaged patients conclude that the left hemisphere is dominant
      for controlling heterogeneous sequences performed by either hand, presumably due
      to the cognitive resources involved in planning complex sequential movements. To
      determine if this lateralized effect is due to asymmetries in primary
      sensorimotor or association cortex, whole-brain functional magnetic resonance
      imaging was used to measure differences in volume of activation while healthy
      right-handed subjects performed repetitive (simple) or heterogeneous (complex)
      finger sequences using the right or left hand. Advanced planning, as evidenced by
      reaction time to the first key press, was greater for the complex than simple
      sequences and for the left than right hand. In addition to the expected greater
      contralateral activation in the sensorimotor cortex (SMC), greater left
      hemisphere activation was observed for left, relative to right, hand movements in
      the ipsilateral left superior parietal area and for complex, relative to simple,
      sequences in the left premotor and parietal cortex, left thalamus, and bilateral
      cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the
      overall MR signal intensity was greater in the left than right SMC, the extent of
      this asymmetry did not vary with hand or complexity level. In contrast, signal
      intensity in the parietal and premotor cortex was greater in the left than right
      hemisphere and for the complex than simple sequences. Signal intensity in the
      caudal anterior cerebellum was greater bilaterally for the complex than simple
      sequences. These findings suggest that activity in the SMC is associated with
      execution requirements shared by the simple and complex sequences independent of
      their differential cognitive requirements. In contrast, consistent with data in
      brain damaged patients, the left dorsal premotor and parietal areas are engaged
      when advanced planning is required to perform complex motor sequences that
      require selection of different effectors and abstract organization of the
      sequence, regardless of the performing hand.

PMID- 15165353
TI  - The relationship of three cortical regions to an information-processing model.
AB  - This research tests a model of the computational role of three cortical regions
      in tasks like algebra equation solving. The model assumes that there is a left
      parietal region-of-interest (ROI) where the problem expression is represented and
      transformed, a left prefrontal ROI where information for solving the task is
      retrieved, and a motor ROI where hand movements to produce the answer are
      programmed. A functional magnetic resonance imaging (fMRI) study of an abstract
      symbol-manipulation task was performed to articulate the roles of these three
      regions. Participants learned to associate words with instructions for
      transforming strings of letters. The study manipulated the need to retrieve these
      instructions, the need to transform the strings, and whether there was a delay
      between calculation of the answer and the output of the answer. As predicted, the
      left parietal ROI mainly reflected the need for a transformation and the left
      prefrontal ROI the need for retrieval. Homologous right ROIs showed similar but
      weaker responses. Neither the prefrontal nor the parietal ROIs responded to
      delay, but the motor ROI did respond to delay, implying motor rehearsal over the
      delay. Except for the motor ROI, these patterns of activity did not vary with
      response hand. In an ACT-R model, it was shown that the activity of an imaginal
      buffer predicted the blood oxygen level-dependent (BOLD) response of the parietal
      ROI, the activity of a retrieval buffer predicted the response of the prefrontal
      ROI, and the activity of a manual buffer predicted the response of the motor ROI.

PMID- 15165354
TI  - The hippocampal system mediates logical reasoning about familiar spatial
      environments.
AB  - It has recently been shown that syllogistic reasoning engages two dissociable
      neural systems. Reasoning about familiar situations engages a frontal-temporal
      lobe system, whereas formally identical reasoning tasks involving unfamiliar
      situations recruit a frontal-parietal visuospatial network. These two systems may
      correspond to the "heuristic" and "formal" methods, respectively, postulated by
      cognitive theory. To determine if this dissociation generalizes to reasoning
      about transitive spatial relations, we studied 14 volunteers using event-related
      fMRI, as they reasoned about landmarks in familiar and unfamiliar environments.
      Our main finding is a task (reasoning and baseline) by spatial content (familiar
      and unfamiliar) interaction. Modulation of reasoning toward unfamiliar landmarks
      resulted in bilateral activation of superior and inferior parietal lobules (BA 7,
      40), dorsal superior frontal cortex (BA 6), and right superior and middle frontal
      gyri (BA 8), regions widely implicated in visuospatial processing. By contrast,
      modulation of the reasoning task toward familiar landmarks, engaged the right
      inferior/orbital frontal gyrus (BA 11/47), bilateral occipital (BA 18, 19), and
      temporal lobes. The temporal lobe activation included the right inferior temporal
      gyrus (BA 37), posterior hippocampus, and parahippocampal gyrus, regions
      implicated in spatial memory and navigation tasks. These results provide support
      for the generalization of dual mechanism theory to transitive reasoning and
      highlight the importance of the hippocampal system in reasoning about familiar
      spatial environments.

PMID- 15165355
TI  - Attention to 3-D shape, 3-D motion, and texture in 3-D structure from motion
      displays.
AB  - We used fMRI to directly compare the neural substrates of three-dimensional (3-D)
      shape and motion processing for realistic textured objects rotating in depth.
      Subjects made judgments about several different attributes of these objects,
      including 3-D shape, the 3-D motion, and the scale of surface texture. For all of
      these tasks, we equated visual input, motor output, and task difficulty, and we
      controlled for differences in spatial attention. Judgments about 3-D shape from
      motion involve both parietal and occipito-temporal regions. The processing of 3-D
      shape is associated with the analysis of 3-D motion in parietal regions and the
      analysis of surface texture in occipito-temporal regions, which is consistent
      with the different behavioral roles that are typically attributed to the dorsal
      and ventral processing streams.

PMID- 15165356
TI  - "What" and "where" in visual working memory: a computational neurodynamical
      perspective for integrating FMRI and single-neuron data.
AB  - Single-neuron recordings, functional magnetic resonance imaging (fMRI) data, and
      the effects of lesions indicate that the prefrontal cortex (PFC) is involved in
      some types of working memory and related cognitive processes. Based on these
      data, two different models of the topographical and functional organization of
      the PFC have been proposed: organization-by-stimulus-domain, and organization-by
      process. In this article, we utilize an integrate-and-fire network to model both
      single-neuron and fMRI data on short-term memory in order to understand data
      obtained in topologically different parts of the PFC during working memory tasks.
      We explicitly model the mechanisms that underlie working memory-related activity
      during the execution of delay tasks that have a "what"-then-"where" design (with
      both object and spatial delayed responses within the same trial). The model
      contains different populations of neurons (as found experimentally) in attractor
      networks that respond in the delay period to the stimulus object, the stimulus
      position, and to combinations of both object and position information. The pools
      are arranged hierarchically and have global inhibition through inhibitory
      interneurons to implement competition. It is shown that a biasing attentional
      input to define the current relevant information (object or location) enables the
      system to select the correct neuronal populations during the delay period in what
      is a biased competition model of attention. The processes occurring at the AMPA
      and NMDA synapses are dynamically modeled in the integrate-and-fire
      implementation to produce realistic spiking dynamics. It is shown that the fMRI
      data characteristic of the dorsal PFC and linked to spatial processing and
      manipulation of items can be reproduced in the model by a high level of
      inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to
      object processing can be produced by a lower level of inhibition, even though the
      network is itself topographically homogeneous with no spatial topology of the
      neurons. This article, thus, not only presents a model for how spatial versus
      object short-term memory could be implemented in the PFC, but also shows that the
      fMRI BOLD signal measured during such tasks from different parts of the PFC could
      reflect a higher level of inhibition dorsally, without this dorsal region
      necessarily being primarily spatial and the ventral region object-related.

PMID- 15165357
TI  - An FMRI study of syntactic adaptation.
AB  - It is easier to produce and comprehend a series of sentences when they have
      similar syntactic structures. This "syntactic priming" effect was investigated
      during silent sentence reading using (i) blood oxygenation level-dependent (BOLD)
      response as a physiological measure in an f MRI study and (ii) reading time as a
      behavioral measure in a complementary self paced reading paradigm. We found that
      reading time and left anterior temporal activation were decreased when subjects
      read sentences with similar relative to dissimilar syntactic forms. Thus,
      syntactic adaptation during sentence comprehension is demonstrated in a neural
      area that has previously been linked to both lexical semantic and sentence
      processing.

PMID- 15165358
TI  - Time course analysis of hippocampal nerve growth factor and antioxidant enzyme
      activity following lateral controlled cortical impact brain injury in the rat.
AB  - Gradual secondary injury processes, including the release of toxic reactive
      oxygen species, are important components of the pathogenesis of traumatic brain
      injury (TBI). The extent of oxidative stress is determined in part by the
      effectiveness of the antioxidant response, involving the enzymes glutathione
      peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Since nerve
      growth factor (NGF) may be involved in the initiation of antioxidant activity, we
      employed a controlled cortical impact injury model in rats to produce secondary
      hippocampal damage and determined the subsequent time course of changes in NGF
      production and GPx, CAT, and SOD activity in this brain region. Hippocampal NGF
      production showed a rapid increase with a biphasic response after TBI. NGF
      protein was increased at 6 h, plateaued at 12 h, declined by 7 days, and
      exhibited a second rise at 14 days after injury. Similar to NGF, hippocampal GPx
      activity also showed a biphasic response, increasing by 12 h, declining at 24 h,
      and exhibiting a second peak at 7 days. In contrast, increased CAT activity
      occured steadily from 1 day through 7 days after injury. SOD activity was
      decreased at 6 h after injury, and continued to decline through 14 days. The
      initial rise in NGF preceded that of CAT, and coincided with an increase in GPX
      and a drop in SOD activity. These data demonstrate a complex temporal spectrum of
      antioxidant enzyme activation following secondary brain injury in the
      hippocampus, and suggest a selective regulatory role for NGF in this response.

PMID- 15165360
TI  - Paradoxical effects of cortical impact injury on environmentally enriched rats.
AB  - Animals housed in an enriched environment develop thicker cortices, with
      increased numbers of dendrites, synapses, blood vessels, and glial cells. This
      study examines the responses of adult rats, developmentally reared in an enriched
      environment, to traumatic brain injury. Rats were placed in an enriched
      environment for 15 days, starting on postnatal day 21. Following enrichment, they
      were placed in standard vivarium conditions until adulthood. At 3 months of age,
      enriched and age-matched control rats received a mild unilateral controlled
      cortical impact and were allowed to recover for 41 days. During this time, they
      were examined for motor coordination deficits and for preferences in forelimb
      use. Results demonstrate that enriched animals had a larger contusion cavity and
      a greater initial deficit in forelimb use. However, this deficit quickly
      diminished in comparison to that seen in non-enriched injured rats. The deficit
      in motor coordination recovered more quickly in enriched rats, 1 week sooner than
      in controls. These data suggest that the response of enriched animals to brain
      injury results in more marked neurodegeneration and acute behavioral dysfunction,
      with a higher capacity for compensation and recovery.

PMID- 15165359
TI  - Differential effects of the anticonvulsant topiramate on neurobehavioral and
      histological outcomes following traumatic brain injury in rats.
AB  - The efficacy of topiramate, a novel therapeutic agent approved for the treatment
      of seizure disorders, was evaluated in a model of traumatic brain injury (TBI).
      Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.),
      subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n =
      47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg,
      i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was
      evaluated using a Morris water maze at 48 h postinjury, after which brain tissue
      was evaluated for regional cerebral edema. In Study B, animals were evaluated for
      motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite
      neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains
      were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss.
      Topiramate had no effect on posttraumatic cerebral edema or histologic damage
      when compared to vehicle. At 48 h, topiramate treatment improved memory function
      in sham but not brain-injured animals, while at one month postinjury it impaired
      learning performance in brain-injured but not sham animals. Topiramate
      significantly improved composite neuroscores at 4 weeks postinjury and rotating
      pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial
      effect on motor function following TBI.

PMID- 15165361
TI  - Comparison of behavioral deficits and acute neuronal degeneration in rat lateral
      fluid percussion and weight-drop brain injury models.
AB  - The behavioral and histological effects of the lateral fluid percussion (LFP)
      brain injury model were compared with the weight drop impact-acceleration model
      with 10 min of secondary hypoxia (WDIA + H). LFP injury resulted in significant
      motor deficits on the beam walk and inclined plane, and memory deficits on the
      radial arm maze and Morris water maze. Motor deficits following LFP remained
      throughout 6 weeks of behavioral testing. WDIA + H injury produced significant
      motor deficits on the beam walk and inclined plane immediately following injury,
      but these effects were transient and recovered by 14 days post-injury. In
      contrast to the LFP injury, the WDIA + H injured animals showed no memory
      deficits on the radial arm maze and Morris water maze. In order to determine if
      the differences in behavioral outcome between models were due to differences in
      injury mechanism or injury severity, 10 LFP-injured animals were matched with 10
      WDIA-injured animals based on injury severity (i.e., time to regain righting
      reflex after brain injury). The LFP-matched injury group showed greater
      impairment than the WDIA + H matched injury group on the radial arm maze and
      Morris water maze. Histological examination of LFP-injured brains with Fluoro
      Jade staining 24 h, 48 h, and 7 days post-injury revealed degenerating neurons in
      the cortex, thalamus, hippocampus, caudate-putamen, brainstem, and cerebellum,
      with degenerating fibers tracts in the corpus callosum and other major tracts
      throughout the brain. Fluoro-Jade staining following WDIA+H injury revealed
      damage to fibers in the optic tract, lateral olfactory tract, corpus callosum,
      anterior commissure, caudate-putamen, brain stem, and cerebellum. While both
      models produce reliable and characteristic behavioral and neuronal pathologies,
      their differences are important to consider when choosing a brain injury model.

PMID- 15165362
TI  - Intraventricular infusion of the neurotrophic protein S100B improves cognitive
      recovery after fluid percussion injury in the rat.
AB  - Elevated serum S100B levels have been shown to be a predictor of poor outcome
      after traumatic brain injury (TBI). Experimental data, on the other hand,
      demonstrate a neuroprotective and neurotrophic effect of this calcium-binding
      protein. The purpose of this study was to examine the role of increased S100B
      levels on functional outcome after TBI. Following lateral fluid percussion or
      sham injury in male Sprague Dawley rats (n = 56), we infused S100B (50 ng/h) or
      vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7 days
      using an osmotic mini-pump. Assessment of cognitive performance by the Morris
      water maze on days 30-34 after injury revealed an improved performance of injured
      animals after S100B infusion (p < 0.05), when compared to vehicle infusion. Blood
      samples for analysis of clinical markers of brain damage, S100B and neuron
      specific enolase, taken at 30 min, 3 h, 4 h, 2 days, or 5 days showed a typical
      peak 3 h after injury (p < 0.01), and higher serum levels correlated
      significantly with an impaired cognitive recovery (p < 0.01). The correlation of
      higher serum S100B levels with poor water maze performance may result from injury
      induced opening of the blood-brain barrier, allowing the passage of S100B into
      serum. Thus while higher serum levels of S100B seem to reflect the degree of
      blood-brain barrier opening and severity of injury, a beneficial effect of
      intraventricular S100B administration on long-term functional recovery after TBI
      has been demonstrated for the first time. The exact mechanism by which S100B
      exerts its neuroprotective or neurotrophic influence remains unknown and needs to
      be elucidated by further investigation.

PMID- 15165363
TI  - A molecular basis for the efficacy of magnesium treatment following traumatic
      brain injury in rats.
AB  - Magnesium ions have been shown to be a promising treatment for brain lesions
      caused by traumatic brain injury (TBI), as well as for the associated acute
      neurodegeneration and progressive functional deficits. This study investigated
      the effects of magnesium on the expression of the cell death/survival related
      proteins following TBI. Male Sprague-Dawley (SD) rats (n = 66, 280-320 g body
      weight) were subjected to sham surgery alone (n = 14), or to the surgery followed
      by a lateral fluid percussion brain injury of moderate severity (n = 52, 2.4-2.7
      atm). The injured rats were randomly treated with an intravenous bolus of
      magnesium chloride (n = 26, 125 micromol) or saline vehicle (n = 26). The coronal
      brain sections were quantitatively analyzed for cell apoptosis and the expression
      of p53-related proteins, Bcl-2, cyclin D1 and PCNA at 1, 2, and 4 days post
      injury by immunohistochemistry or in situ hybridization. Tissue damage was
      observed primarily in the ipsilateral cortex of the injured region with the
      induction of apoptosis and p53 mRNA level at 2 days after TBI. The expression of
      p53 and responding proteins (p21(WAF1/CIP1), Mdm2 and Bax) showed a temporal
      pattern similar to the apoptotic events in the time course experiments. They were
      induced in the early time points of days 1-2, decreasing by day 4 after TBI. In
      contrast, the expression of the cell survival related proteins - Bcl-2, cyclin
      D1, and PCNA - was most significant at day 4 post-injury, when the rate of
      apoptosis decreased. Magnesium treatment resulted in a reduction in apoptosis and
      expression of p53-related proteins. However, it had only a slight additive effect
      on the expression of the survival related proteins in the same time-course. These
      results provide a molecular basis for the efficiency of magnesium in treating TBI
      induced tissue damage.

PMID- 15165364
TI  - Acute subdural hematoma associated with diffuse brain injury and hypoxemia in the
      rat: effect of surgical evacuation of the hematoma.
AB  - The aim of this study was to assess the effect of rapid or delayed surgical
      evacuation on the physiological consequence and brain edema formation in a rat
      model of acute subdural hematoma (SDH) coupled with either diffuse brain injury
      (DBI) or hypoxemia. The SDH was made by an autologous blood injection, while DBI
      was induced using the impact acceleration model (mild, 450 g/1 m; severe, 450 g/2
      m). Physiological parameters measured included intracranial pressure (ICP), mean
      arterial blood pressure (MABP), cerebral blood flow (CBF), and brain tissue water
      content. At 1 h (rapid evacuation) or 4 h (delayed evacuation) after the SDH
      induction, surgical evacuation following a craniotomy was performed using saline
      irrigation and forceps. The study consisted of three different series, including
      400 microL of SDH alone (Series 1), SDH400 + mild DBI (Series 2), and SDH300 +
      severe DBI + 20 min hypoxemia (Series 3). The hypoxemia was added in Group 3 to
      produce a steadily increasing ICP. In Series 1 and 2, all rats were randomized
      into the three following groups: non-, rapid, and delayed evacuation; Series 3
      had two groups: non- and rapid evacuation. In Series 1, the surgical evacuation
      showed no beneficial effects on the brain edema formation assessed at 5 h post
      injury. In Series 2, the rapid, but not delayed, evacuation significantly reduced
      both the increased ICP level and brain water content. The additional insult of
      hypoxemia (Series 3) resulted in a progressive ICP elevation, persistently
      depressed CBF, and severe brain swelling. Under this situation, the rapid
      evacuation exacerbated brain edema. These results have clinical implications for
      the management of severe traumatic SDH, especially its operative indication and
      timing.

PMID- 15165365
TI  - The effects of admission alcohol level on cerebral blood flow and outcomes after
      severe traumatic brain injury.
AB  - This study examined the relationship between admission serum alcohol level (ETOH)
      and cerebral blood flow (CBF) and outcomes in the adult traumatic brain injured
      (TBI) population. We hypothesized that individuals with ETOH > 100 mg/dL will
      have decreased blood flow on admission and poorer outcomes. Eighty subjects, age
      16-65, with severe TBI (Glasgow Coma Score [GCS] </= 8) were entered into the
      study. Correlational analysis assessed the relationship between ETOH and
      admission severity of injury scores as measured by Marshall and APACHE III
      scores, CBF, and outcomes. Comparison of CBF and outcomes between groups based on
      admission serum ETOH level was conducted with analysis of variance and post hoc
      Scheffe analyses as well as regression analysis. There was a significant
      relationship between serum ETOH level and GCS (p = 0.02), but not APACHE III
      scores (p = 0.12) or Marshall scores (p = 0.27). There was a significant
      correlation between global CBF and serum ETOH level (p = 0.02). There was no
      statistically significant association between serum ETOH level and GOS at 3 (p =
      0.97), 6 (p= 0.56), or 12 (p = 0.73) months after injury. The data indicated that
      serum ETOH levels > 100 mg/dL at the time of admission after a TBI were
      associated with a decrease in global CBF. Elevated serum ETOH level at time of
      injury did not, however, impact outcomes.

PMID- 15165366
TI  - Morphological changes of cerebral ventricular wall in traumatic brain injury
      evaluated via large histological specimens.
AB  - Large brain specimens were prepared from 50 head-injured and 50 non-head-injured
      cases that underwent medicolegal autopsy to critically examine the morphological
      changes in the periventricular tissue caused by injury to the head. Hemorrhagic
      damage to the ventricular wall was observed in 30 (60%) of the head-injury cases
      but was not observed in any of the non-head injured cases. Of 14 cases with only
      wounds to the scalp, five cases (35.7%) had ventricular wall damage. Of 40 cases
      in which death occurred within 24 h after injury, 25 (62.5%) showed ventricular
      wall damage. Of five cases of dying more than 24 h post-injury, only one revealed
      ventricular wall damage. This ventricular wall damage was frequently detected in
      the posterior (46%) and anterior horns (19%) of the lateral ventricle, near the
      attachment of the choroid plexus (19%). These morphological changes are
      considered primary damage, formed at the moment of impact in that concomitant
      hemorrhagic damage to the ventricular wall was also observed in all immediate
      death cases. Accordingly, detection of ventricular wall damage is considered a
      reliable means for deducing the occurrence of traumatic injury even in the cases
      where death occurs soon after injury.

PMID- 15165367
TI  - A no-laminectomy spinal cord compression injury model in mice.
AB  - The purpose of this study was to develop a minimally invasive recovery model of
      spinal cord injury in the C57Bl/6J mouse. Without laminectomy, the epidural space
      was exposed by disruption of the T10-T11 interspinous ligament. Perpendicular to
      the rostral-caudal axis of the spine, a 1.5-mm silicone tube (O.D. 0.047 in.) was
      placed in the T11 epidural space. Prior to placement, a suture was passed through
      the tube allowing withdrawal of the tube after discontinuation of anesthesia.
      After 1, 30, 60, or 120 min (n = 5-8) of spinal cord compression (SCC), the tube
      was withdrawn. Neurological function was measured at 1, 3, 7, and 14 days after
      injury followed by histologic analysis. BBB locomotor score, rotarod latency, and
      screen grasping were worsened in a SCC duration-dependent manner (p < 0.0001).
      With increasing SCC duration, the number of histologically normal neurons in the
      ventral horns decreased (p < 0.0001) while the cross-sectional area of spinal
      cord with pancellular necrosis increased (p < 0.0001). Increased duration of SCC
      caused progressive rostral-caudal spread of histologic damage. The results
      indicate that this is a simple, reliable model with neurologic and histologic
      injury highly dependent on SCC duration. This model may be useful for study of
      spinal cord injury in genetically modified mice in the absence of anesthetic
      confounds while leaving the vertebral column intact.

PMID- 15165368
TI  - Activation of microglial cells and complement following traumatic injury in rat
      entorhinal-hippocampal slice cultures.
AB  - The complement cascade has been suggested to be involved in development of
      secondary brain damage following traumatic brain injury (TBI). Previous studies
      have shown that reactive microglia are involved in activation of the complement
      cascade following various injuries to the nervous system. Macrophages seem to
      have a significant role in this process, but it is still unclear whether these
      cells, as well as the complement components, are derived from reactive microglia
      or if these biological events only can occur as a result from the influx of
      plasma and monocytes via a disrupted blood-brain barrier (BBB). The aim of this
      study was to investigate the response of microglial cells and the complement
      system in the absence of plasma/blood components following a standardized crush
      injury in an entorhinal-hippocampal slice culture. There was a clear increase in
      complement component C1q and C5b-9-IR (Membrane Attack Complex, MAC) in the area
      near the crush injury. MAC-IR appeared as numerous dots in clusters which co
      localized with anti-NeuN labelled neurons in the injury border zone. Complement
      C1q-IR co-localized with reactive microglia, co-labelled with OX42 antisera.
      These findings show activation of the complement cascade near the injury zone and
      in particular, formation of MAC at the surface of neurons in this area. There was
      a distinct activation of microglial cells (OX42-IR) near the site of injury, as
      well as an increase in ED-1 expressing macrophages. In the absence of blood and
      plasma components it is likely that ED-1-labelled cells represent reactive
      microglia transformed into macrophages. In addition, Neurons (Neun-IR) near the
      injury were found to co-localize with clusterin-IR indicating upregulation of a
      defense system to the endogenous complement attack. The present study provides
      evidence that microglia and complement is activated in the injury border zone of
      the tissue slice in a similar fashion as in vivo following TBI, despite the
      absence of plasma/blood products and cells. These findings support the hypothesis
      that reactive microglia have a key role in complement activation following TBI by
      local synthesis of complement with a potential impact on development of secondary
      neuronal insults.

PMID- 15165369
TI  - Synergistic effect of Nogo-neutralizing antibody IN-1 and ciliary neurotrophic
      factor on axonal regeneration in adult rodent visual systems.
AB  - The presence of Nogo axon regeneration inhibitory molecules in the central
      nervous system (CNS) and the counteracting effect of IN-1 antibodies have been
      widely reported. In this study, we examined the effect of IN-1-producing
      hybridoma cells on axon regeneration in adult rodent retinal ganglion cells
      (RGCs) after various types of optic nerve (ON) injury, evaluating therein whether
      ciliary neurotrophic factor (CNTF) potentiated the effect of IN-1. We found that
      application of IN-1 alone failed to enhance regeneration of intracranially or
      intraorbitally transected RGC axons in a peripheral nerve (PN) graft. IN-1
      hybridoma cells also failed to significantly promote intraorbitally crushed ON
      axons to reenter the distal part of the ON. However, a combined application of IN
      1 and CNTF had a synergistic effect in both intracranial PN and intraorbital ON
      crush paradigms. This study suggests that the action of IN-1 antibodies in
      promoting axon regeneration in the CNS could be more effective when coupled with
      other appropriate factors.

PMID- 15165370
TI  - Methodological evaluation to analyze functional recovery after sciatic nerve
      injury.
AB  - The Basso, Bresnahan and Beattie (BBB) locomotor scale has not been tested to
      evaluate functional consequences of peripheral nerve lesions. Alternative methods
      to evaluate animal functional recovery after sciatic nerve injury are desirable.
      Male Wistar rats had a right sciatic nerve segment exposed and were divided in
      three experimental groups: Sham (wound open, 10 min), Sham-device (nerve segment
      between crushing device, 10 min), and Crush-force (nerve crushing load of 15,000
      g/1,000 mm Hg/mm(2), 10 min). Animals were evaluated preoperatively, 1, 7, 14,
      21, and 28 days after procedure by calculation of Sciatic Functional Index (SFI),
      BBB score and open arena exploratory activity. The primary findings of the
      present study were (1) the SFI calculated by either DeMedinaceli, Carlton and
      Goldberg, and Bain formulae were highly correlated; (2) the BBB score evaluation
      was highly correlated with the SFI; (3) the BBB motor scale was able to detect
      functional impairments not recognized by the SFI; and (4) open arena exploratory
      activity was a poor method to detect sciatic nerve impairment. In conclusion, the
      BBB prescribed functional deficits on the sham-device and crush-force groups even
      when the SFI indicated full recovery. This greater sensitivity may prove useful
      when comparing new therapeutic approaches to nerve regeneration.

PMID- 15165371
TI  - The tale of Phineas Gage, digitally remastered.
AB  - The injury of Phineas Gage has fueled research on and fascination with the
      localization of cerebral functions in the past century and a half. Most
      physicians and anatomists believed that Gage sustained a largely bilateral injury
      to the frontal lobes. However, previous studies seem to have overlooked a few
      less obvious, but essential details. This has led us to reanalyze the injury
      using three-dimensional reconstruction and quantitative computer-aided techniques
      and to propose a new biomechanical model, in order to determine the location and
      extent of the injury and explain Gage's improbable survival. Unlike previous
      studies on this subject, our findings are based on computer-generated three
      dimensional reconstructions of a thin-slice computed tomography scan (CAT) of
      Phineas Gage's skull. The results of our image analysis were corroborated with
      the clinical findings, thoroughly recorded by Dr. Harlow in 1848, as well as with
      a systematic examination of the original skull specimen. Our results show that
      the cerebral injury was limited to the left frontal lobe, did not extend to the
      contralateral side, did not affect the ventricular system, and did not involve
      vital intracranial vascular structures. Although modern neuroscience has perhaps
      outgrown the speculations prompted by this famous case, it is still a living part
      of the medical folklore and education. Setting the record straight based on
      clinical reasoning, observation of the physical evidence, and sound quantitative
      computational methods is more than mere minutia and of interest for the broad
      medical community.

PMID- 15165373
TI  - Educational needs of family caregivers of persons living with HIV/AIDS in
      Thailand.
AB  - As the AIDS epidemic continues to overwhelm the acute care hospital system in
      Thailand, an increasing number of family members are required to provide care for
      persons living with AIDS (PLWA) in their homes. In response to the increasing
      demand for home care, a qualitative study using focus group methodology was
      conducted to learn more about the need for education and support for family
      caregivers of PLWA in Thailand. Eighteen family caregivers and 18 nurses caring
      for PLWA participated in four focus group discussions. The major themes
      identified were fear, stigma, sorrow, empathy, hopelessness, and hope. In
      addition, participants voiced a need for education to improve the knowledge and
      skills related to care of PLWA. These findings will be used to guide the
      development of a training program for family caregivers.

PMID- 15165374
TI  - An exploration of socioeconomic, spiritual, and family support among HIV-positive
      women in India.
AB  - Through in-depth, tape-recorded interviews, this qualitative pilot study explored
      the feelings and concerns of 10 HIV-positive women, aged 18 to 70 years, and the
      socioeconomic, spiritual, and family support available to them in Kolkata, India.
      A qualitative approach of continuous comparative analysis of themes revealed that
      although heterosexual contact was the main source of infection, poverty and
      sexual violence were indirect social factors. These women experienced markedly
      less socioeconomic, spiritual, and family support after contracting the disease.
      In addition to worsening physical symptoms, emotional and mental anguish forced
      them into isolation, negatively affecting their mental health. Social isolation
      infiltrated their spiritual lives, producing feelings of helplessness about the
      future of their children. The identification of this process is important to
      nursing practice, as it highlights key areas of concern in the implementation of
      prevention programs and future research.

PMID- 15165375
TI  - The Advanced Nursing Practice Team as a model for HIV/AIDS caregiving in
      Switzerland.
AB  - To offer advanced nursing care for people living with HIV, a participatory action
      research project was initiated that enabled constant learning and change at the
      levels of (a) the culture and organization of an outpatient department, (b)
      clinical leadership and interdisciplinary collaboration, and (c) development of
      new services. In this project, the development of the Advanced Nursing Practice
      (ANP) Team not only affected the practice of individual nurses with advanced
      degrees but also created a team of nurses educated at different levels. Through a
      systematic process, the nurses on the team became more educated and refined their
      clinical expertise. An essential aspect of the ANP Team was the specialization of
      each nurse in a self-selected topic within HIV/AIDS care. As members of the ANP
      Team, the nurses offer state-of-the-art nursing care including patient
      assessment, medication management and adherence support, symptom management,
      health maintenance and prevention, and family support for persons living with
      HIV.

PMID- 15165376
TI  - Knowledge, attitude, and practice about AIDS and condom utilization among health
      workers in Rwanda.
AB  - Health workers in rural Rwanda were surveyed cross-sectionally on knowledge,
      attitude, and practice (KAP) about AIDS, HIV, and condom utilization.
      Participants were 350 health workers from six randomly chosen communities (three
      rural, three semirural). In general, knowledge about HIV/AIDS was moderate to
      good, with an average of 63% of the questions answered correctly; men (and
      younger respondents) had a better knowledge than did women (p =.01; older
      participants, p =.015). However, in the specific area of HIV/AIDS symptoms,
      knowledge was inadequate. In general, the attitude of health workers toward
      condoms was not sufficiently positive. Regular use of condoms was reported by
      17%; the only variable significantly associated with condom use was having more
      than one partner during the past year. Men and those who scored high on knowledge
      had a more positive attitude toward infected individuals than did women (p =.003)
      and those with less knowledge (p =.001). In conclusion, there is an urgent need
      to institute educational programs to reduce the stigma about condoms among health
      workers in Rwanda.

PMID- 15165377
TI  - Attitudes of nursing and auxiliary hospital staff toward HIV infection and AIDS
      in Spain.
AB  - The aim of this study was to determine the attitudes of health personnel staff
      concerning HIV and AIDS. Participants included nurses (n = 315) and nurses' aides
      (auxiliary staff) (n = 115) working from May to June 2002 in a Spanish hospital.
      A self-administered validated questionnaire about attitudes towards HIV and AIDS
      was used. The response was 74.9% (N = 430). The mean for the attitudes
      questionnaire was 79.7 (SD = 10.9), with a median of 80. The nurses had more
      positive attitudes than the auxiliary workers (80.9 vs. 76.5; t = 3.712; p<.001).
      Twenty percent (n = 63) of the nurses and 37.4% (n = 43) of the auxiliary workers
      (p<.001) reported a negative attitude. After a logistic regression analysis
      adjusting for age, sex, and occupations, the authors found that age and
      occupation were the variables with an independent effect on attitudes toward HIV.

PMID- 15165378
TI  - Experiences of HIV-positive women in Sydney, Australia.

PMID- 15165379
TI  - Nursing, health, and human rights: a framework for international collaboration.

PMID- 15165380
TI  - Optimal dye concentration and irradiance for laser-assisted vascular anastomosis.
AB  - OBJECTIVE: This investigation was done in order to find optimal indocyanine green
      (ICG) concentration and energy irradiance in laser vascular welding. BACKGROUND
      DATA: Many studies have shown that laser tissue welding with albumin solder/ICG
      may be an effective technique in surgical reconstruction. However, there are few
      reports regarding optimal laser settings and concentrations of ICG within the
      albumin solder in laser-assisted vascular anastomosis. MATERIALS AND METHODS:
      Porcine carotid artery strips (n = 120) were welded in end-to-end by diode laser
      with 50% albumin solder of 0.01, 0.1, and 1.0 mM ICG at irradiance of 27.7, 56.7,
      and 76.9 W/cm(2), respectively. Temperature was measured by inserting
      thermocouples outside and inside the vessel. Tensile strength and histology were
      studied. RESULTS: Temperature and strength of the anastomosis significantly
      decreased (all p < 0.05) with increasing ICG concentration at 56.7 W/cm(2).
      Histological study showed minimal thermal injury limited to adventitia and no
      appreciable difference between all groups. CONCLUSIONS: ICG concentration within
      solder is the most important factor affecting both vascular temperature and
      tensile strength. The optimal balance between strength and minimal thermal injury
      may be achieved primarily at 56.7 W/cm(2) and 0.01 mM ICG.

PMID- 15165382
TI  - Evaluation of trans-scleral diode laser using diopexy probe for subfoveal
      choroidal neovascular membrane in age-related macular degeneration.
AB  - OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic
      effects of trans-scleral diode laser photocoagulation in patients with subfoveal
      choroidal neovascularization from age-related macular degeneration (ARMD).
      BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal
      neovascularization in ARMD is still unsatisfactory. Various forms of therapy such
      as laser treatment, photodynamic therapy, radiation therapy, transpupillary
      thermotherapy, and surgical excision have been tried with variable results.
      MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were
      treated with trans-scleral diode laser using the diopexy probe under indirect
      ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized
      protocol refraction, visual acuity testing, reading speed, contrast requirement
      measurement, ophthalmic examinations, color fundus photographs, and fluorescein
      angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes
      of 18 patients were included in the study between April 2000 and May 2002. At 12
      weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity
      score, and one patient showed improvement (gain of more than five letters) in
      letter visual acuity score. Reading speed levels and contrast requirement were
      found to be similar to pre-laser level at 3 months followup. At 12 weeks,
      moderate fluorescein leakage was seen in one eye, minimal leakage was seen in
      five eyes, absence of leakage was seen in 10 eyes, and progression was seen in
      two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal
      neovascular membranes in ARMD may be an effective as well as safe alternative in
      the management of these patients.

PMID- 15165381
TI  - Cleaning of the root canal using Nd:YAP laser and its effect on the mineral
      content of the dentin.
AB  - OBJECTIVE: To compare the efficacy of root canal cleanliness with and without
      Nd:YAP laser and to assess the effect of the laser on the mineral content of the
      dentin. BACKGROUND DATA: A high degree of cleanliness of the canal when using
      Nd:YAG laser has been shown while the laser had been in contact with the canal
      wall. A new Nd:YAP laser has been studied recently, which is considered to be
      superior to Nd:YAG with regard to antibactericidal ability due to its 1.34-mu
      wavelength, which is in the infra red range. This wavelength is absorbed better
      in water that of Nd:YAG. MATERIALS AND METHODS: Fourteen extracted single rooted
      premplars were divided into two groups. In group 1, canals were cleaned,
      instrumented and shaped with K files. In group 2, initial preparation was done
      using K files and completed with a Nd:YAP laser. Teeth were then split
      longitudinally and submitted to SEM. RESULTS: The cleanliness of the laser
      treated teeth was significantly greater than teeth treated with K files alone
      (p<0.05). No difference in Ca and P content was detected when the use of K files
      was compared to the use of laser. CONCLUSIONS: It appears that Nd:YAP laser
      improves the cleanliness of the root canal. However, since Nd:YAP laser serves as
      an addition to K files, its clinical value for replacing conventional root canal
      instrumentation remains to be determined.

PMID- 15165383
TI  - Safety parameters for pulp temperature during selective ablation of caries by KTP
      laser in vitro.
AB  - OBJECTIVE: To define the optimal parameters of KTP laser irradiation during a
      selective caries removal. MATERIALS AND METHODS: Twelve decayed human teeth,
      recently extracted were used. Their root canals were prepared for insertion of a
      thermocouple probe into the pulp chamber. The demineralized tissues were colored
      by Acid Red 52 before proceeding to different conditions of irradiation. RESULTS:
      Pulpal temperature increases (below 3 degrees C) were found under the following
      parameters with 15 sec of continuous lasing: 400 mWatts, 0.10-msec pulse width,
      PRR <50 Hz for efficient caries removal. A resting time average of 70 sec was
      necessary to allow pulp temperature to get back to its baseline. CONCLUSION: KTP
      laser can be used safely and without any pulp over-heating under certain
      irradiation conditions.

PMID- 15165384
TI  - Investigation of the supplementary effect of GaAs laser therapy on the
      rehabilitation of human digital flexor tendons.
AB  - OBJECTIVE: To investigate the effect of laser photostimulation in rehabilitation
      of human digital flexor tendons with a placebo-controlled double-blind
      prospective study model. BACKGROUND DATA: Low-energy laser therapy has been
      applied in several rheumatoid and soft tissue disorders with a varying rate of
      success and it has also been shown to have a positive effect on tendon healing in
      animal experiments, but no clinical study on laser photostimulation in the
      treatment of human tendons has been reported to date. MATERIALS AND METHODS: This
      study was performed in a total of 25 patients with 41 digital flexor tendon
      injuries in five anatomical zones. In Group I (21 digits in 13 patients),
      whirlpool and infrared GaAs diode laser with a frequency of 100 Hz. was applied
      between the 8th and 21st days postoperatively and all patients were given the
      Washington rehabilitation program until the end of the 12th week. In Group II (20
      digits in 12 patients), the same treatment protocol was given but the laser
      instrument was switched off during applications. RESULTS: The results of the
      study showed a significant improvement in the laser-treated group only for the
      parameter of edema reduction (p < 0.01) but the difference between the two groups
      was non-significant for pain reduction, hand grip strength, and functional
      evaluation performed according to Strickland and Buck-Gramcko systems using total
      active motion and fingertip-to distal palmar crease distance parameters (p >
      0.05). CONCLUSIONS: Significant improvement obtained in edema reduction both
      immediately and 12 weeks after supplementary GaAs laser application in our study
      has been interpreted as an important contribution to the rehabilitation of human
      flexor tendon injuries because edema is known to have a detrimental effect on
      functional recovery during both early and late stages of tendon healing. However,
      our study has failed to show a significant positive effect of supplementary GaAs
      laser application on the other functional recovery parameters of human flexor
      tendon injury rehabilitation and we suggest further clinical study in this topic
      be done using different laser types and dosages in order to delineate the role of
      this promising treatment modality.

PMID- 15165385
TI  - Effect of low-intensity (3.75-25 J/cm2) near-infrared (810 nm) laser radiation on
      red blood cell ATPase activities and membrane structure.
AB  - OBJECTIVE: The biostimulation and therapeutic effects of low-power laser
      radiation of different wavelengths and light doses are well known, but the exact
      mechanism of action of the laser radiation with living cells is not yet
      understood. The aim of the present work was to investigate the effect of laser
      radiation (810 nm, radiant exposure 3.75-25 J/cm(2)) on the structure of protein
      and lipid components of red blood cell membranes and it functional properties.
      The role of membrane ATPases as possible targets of laser irradiation was
      analyzed. BACKGROUND DATA: A variety of studies both in vivo and in vitro showed
      significant influence of laser irradiation on cell functional state. At the same
      time another group of works found no detectable effects of light exposure. Some
      different explanations based on the light absorption by primary endogenous
      chromophores (mitochondrial enzymes, cytochromes, flavins, porphyrins) have been
      proposed to describe biological effects of laser light. It was suggested that
      optimization of the structural-functional organization of the erythrocyte
      membrane as a result of laser irradiation may be the basis for improving the
      cardiac function in patients under a course of laser therapy. MATERIALS AND
      METHODS: Human red blood cells or isolated cell membranes were irradiated with
      low-intensity laser light (810 nm) at different radiant exposures (3.75-25
      J/cm(2)) and light powers (fluence rate; 10-400 mW) at 37 degrees C. As the
      parameters characterizing the structural and functional changes of cell membranes
      the activities of Na(+)-, K(+)-, and Mg(2+)-ATPases, tryptophan fluorescence of
      membrane proteins and fluorescence of pyrene incorporated into membrane lipid
      bilayer were used. RESULTS: It was found that near-infrared low-intensity laser
      radiation changes the ATPase activities of the membrane ion pumps in the dose-
      and fluence rate-dependent manner. At the same time no changes of such integral
      parameters as cell stability, membrane lipid peroxidation level, intracellular
      reduced glutathione or oxyhaemoglobin level were observed. At laser power of 10
      mW, an increase of the ATPase activity was observed with maximal effect at 12-15
      J/cm(2) of light dose (18-26% for the total ATPase activity). At laser power of
      400 mW (fluence rate significantly increased), inhibition of ATPases activities
      mainly due to the inhibition of Na(+)-, K(+)-ATPase was observed with maximal
      effect at the same light dose of 12-15 J/cm(2) (18-23% for the total ATPase
      activity). Fractionation of the light dose significantly changed the membrane
      response to laser radiation. Changes in tryptophan fluorescent parameters of
      erythrocyte membrane proteins and the increase in lipid bilayer fluidity measured
      by pyrene monomer/excimer fluorescence ratio were observed. CONCLUSIONS: Near
      infrared laser light radiation (810 nm) induced long-term conformational
      transitions of red blood cell membrane which were related to the changes in the
      structural states of both erythrocyte membrane proteins and lipid bilayer and
      which manifested themselves as changes in fluorescent parameters of erythrocyte
      membranes and lipid bilayer fluidity. This resulted in the modulation of membrane
      functional properties: changes in the activity of membrane ion pumps and, thus,
      changes in membrane ion flows.

PMID- 15165386
TI  - Morpho-structural aspects of Er:YAG-prepared class V cavities.
AB  - OBJECTIVE: The aim of this study was to evaluate the ability of an Er:YAG laser
      (2960nm) to prepare class V cavities as compared with rotary instruments.
      MATERIALS AND METHODS: Twenty-six freshly extracted human molars were selected
      and randomly distributed in two groups. Non standardized class V cavities were
      prepared using (group 1) a diamond bur for enamel, plus a tungsten bur for dentin
      with water irrigation and (group 2) an Er:YAG laser (output parameters, enamel:
      1000 mJ, 12Hz, dentin: 500 mJ, 20Hz) with a continuous flow of water. RESULTS:
      The SEM examination revealed characteristic micro-irregularities of the lased
      samples as compared with the conventional prepared cavities: group 1, the walls
      of the cavities were slightly curved and a smear layer plus muds covered
      peripheric walls as well as the depth of the cavity; rare dentinal tubules were
      opened; linear and circular surface irregularities were observed on the dentin;
      and group 2, the walls of the cavities were irregular, jagged; photo-ablation
      creates a real cleavage of hydroxyapatite prisms with respect to the enamel prism
      pathway; an homogeneous dentin with opened dentinal tubules covered the depth of
      the cavities; intertubular dentin is selectively more ablated than Er-YAG the
      peritubular dentin. CONCLUSIONS: Jagged outline as well as opened dentinal
      tubules are the main characteristics of the Er-YAG prepared class V cavities.
      Further investigations (ulstrastructural, histochemical properties of the lased
      dentin, resistance to traction of bonded resins) should be conducted.

PMID- 15165387
TI  - Low-level laser treatment can reduce edema in second degree ankle sprains.
AB  - OBJECTIVE: Low-level laser therapy (LLLT) has been used for the last few years to
      treat sports injuries. The purpose of this study was to compare three therapeutic
      protocols in treating edema in second degree ankle sprains that did not require
      immobilization with a splint, under placebo-controlled conditions. MATERIALS AND
      METHODS: Forty-seven soccer players with second degree ankle sprains, selected at
      random, were divided into the following groups: The first group (n = 16) was
      treated with the conventional initial treatment (RICE, rest, ice, compression,
      elevation), the second group (n = 16) was treated with the RICE method plus
      placebo laser, and the third group (n = 15) was treated with the RICE method plus
      an 820-nm GaA1As diode laser with a radiant power output of 40 mW at 16 Hz.
      Before the treatment, and 24, 48, and 72 h later, the volume of the edema was
      measured. RESULTS: A three by three repeated measures ANOVA with a follow up post
      hoc test revealed that the group treated with the RICE and an 820-nm GaA1As diode
      laser presented a statistically significant reduction in the volume of the edema
      after 24 h (40.3 +/- 2.4 mL, p < 0.01), 48 h (56.4 +/- 3.1 mL, p < 0.002), and 72
      h (65.1 +/- 4.4 mL, p < 0.001). CONCLUSIONS: LLLT combined with RICE can reduce
      edema in second-degree ankle sprains.

PMID- 15165389
TI  - Photobiological basis and clinical role of low-intensity lasers in biology and
      medicine.
AB  - The purpose of this article is to provide a comprehensive review on the clinical
      role of low intensity laser therapy (laser photostimulation) in biology and
      medicine. Studies on wound healing and pain relief are highlighted to show the
      clinical efficacy of laser therapy. Controversies about the use of low intensity
      laser as a therapeutic modality for wound healing and pain relief are presented
      and a brief explanation is provided to overcome these controversies. The
      importance of standard parameters is emphasized for the applications of low
      intensity lasers in biology and medicine. A justification has been made to
      warrant further research on the use of low intensity laser as a therapeutic
      modality. Although the therapeutic applications of low intensity laser are
      imminent, the heterogeneity in treatment protocols and study design calls for a
      vigilant interpretation of the findings.

PMID- 15165388
TI  - Comparative study of dentine permeability after apicectomy and surface treatment
      with 9.6 microm TEA CO2 and Er:YAG laser irradiation.
AB  - Failure of apicectomies is generally attributed to dentine surface permeability
      as well as to the lack of an adequate marginal sealing of the retrofilling
      material, which allows the percolation of microorganisms and their products from
      the root canal system to the periodontal region, thus compromising periapical
      healing. The purpose of this study was to evaluate dentine and the marginal
      permeability after apicectomy and surface treatment with 9.6 micro m TEA CO(2) or
      Er:YAG 2.94 micro m laser irradiation. Sixty-five single rooted human
      endodontically treated teeth were divided into five experimental groups: group I
      (control), apicectomy with high speed bur; group II, similar procedure to that of
      group I, followed by dentinal surface treatment with 9.6 micro m CO(2) laser;
      group III, similar procedure to group I followed by dentinal surface treatment
      with Er:YAG laser 2.94 micro m; group IV, apicectomy and surface treatment with
      CO(2) 9.6 micro m laser; and group V, apicectomy and surface treatment with
      Er:YAG laser 2.94 micro m. The analysis of methylene blue dye infiltration
      through the dentinal surface and the retrofilling material demonstrated that the
      samples from the groups that were irradiated with the lasers showed significantly
      lower infiltration indexes than the ones from the control group. These results
      were compatible with the structural morphological changes evidenced through SEM
      analysis. Samples from groups II and IV (9.6 micro m CO(2)) showed clean smooth
      surfaces, fusion, and recrystallized dentine distributed homogeneously throughout
      the irradiated area sealing the dentinal tubules. Samples from groups III and V
      (Er:YAG 2.94 micro m) also presented clean surfaces, without smear layer, but
      roughly compatible to the ablationed dentine and without evidence of dentinal
      tubules. Through the conditions of this study, the Er:YAG 2.94 micro m and the
      9.6 micro m CO(2) laser used for root canal resection and dentine surface
      treatment showed a reduction of permeability to methylene blue dye.

PMID- 15165391
TI  - Laser literature watch.

PMID- 15165392
TI  - Bayesian estimation of stimulus responses in Poisson spike trains.
AB  - A Bayesian method is developed for estimating neural responses to stimuli, using
      likelihood functions incorporating the assumption that spike trains follow either
      pure Poisson statistics or Poisson statistics with a refractory period. The
      Bayesian and standard estimates of the mean and variance of responses are similar
      and asymptotically converge as the size of the data sample increases. However,
      the Bayesian estimate of the variance of the variance is much lower. This allows
      the Bayesian method to provide more precise interval estimates of responses.
      Sensitivity of the Bayesian method to the Poisson assumption was tested by
      conducting simulations perturbing the Poisson spike trains with noise. This did
      not affect Bayesian estimates of mean and variance to a significant degree,
      indicating that the Bayesian method is robust. The Bayesian estimates were less
      affected by the presence of noise than estimates provided by the standard method.

PMID- 15165393
TI  - Comments on "a parallel mixture of SVMs for very large scale problems".
AB  - Collobert, Bengio, and Bengio (2002) recently introduced a novel approach to
      using a neural network to provide a class prediction from an ensemble of support
      vector machines (SVMs). This approach has the advantage that the required
      computation scales well to very large data sets. Experiments on the Forest Cover
      data set show that this parallel mixture is more accurate than a single SVM, with
      90.72% accuracy reported on an independent test set. Although this accuracy is
      impressive, their article does not consider alternative types of classifiers. We
      show that a simple ensemble of decision trees results in a higher accuracy,
      94.75%, and is computationally efficient. This result is somewhat surprising and
      illustrates the general value of experimental comparisons using different types
      of classifiers.

PMID- 15165394
TI  - Automated algorithms for multiscale morphometry of neuronal dendrites.
AB  - We describe the synthesis of automated neuron branching morphology and spine
      detection algorithms to provide multiscale three-dimensional morphological
      analysis of neurons. The resulting software is applied to the analysis of a high
      resolution (0.098 microm x 0.098 microm x 0.081 microm) image of an entire
      pyramidal neuron from layer III of the superior temporal cortex in rhesus macaque
      monkey. The approach provides a highly automated, complete morphological analysis
      of the entire neuron; each dendritic branch segment is characterized by several
      parameters, including branch order, length, and radius as a function of distance
      along the branch, as well as by the locations, lengths, shape classification
      (e.g., mushroom, stubby, thin), and density distribution of spines on the branch.
      Results for this automated analysis are compared to published results obtained by
      other computer-assisted manual means.

PMID- 15165395
TI  - Computing and stability in cortical networks.
AB  - Cortical neurons are predominantly excitatory and highly interconnected. In spite
      of this, the cortex is remarkably stable: normal brains do not exhibit the kind
      of runaway excitation one might expect of such a system. How does the cortex
      maintain stability in the face of this massive excitatory feedback? More
      importantly, how does it do so during computations, which necessarily involve
      elevated firing rates? Here we address these questions in the context of
      attractor networks-networks that exhibit multiple stable states, or memories. We
      find that such networks can be stabilized at the relatively low firing rates
      observed in vivo if two conditions are met: (1) the background state, where all
      neurons are firing at low rates, is inhibition dominated, and (2) the fraction of
      neurons involved in a memory is above some threshold, so that there is sufficient
      coupling between the memory neurons and the background. This allows "dynamical
      stabilization" of the attractors, meaning feedback from the pool of background
      neurons stabilizes what would otherwise be an unstable state. We suggest that
      dynamical stabilization may be a strategy used for a broad range of computations,
      not just those involving attractors.

PMID- 15165396
TI  - Real-time computation at the edge of chaos in recurrent neural networks.
AB  - Depending on the connectivity, recurrent networks of simple computational units
      can show very different types of dynamics, ranging from totally ordered to
      chaotic. We analyze how the type of dynamics (ordered or chaotic) exhibited by
      randomly connected networks of threshold gates driven by a time-varying input
      signal depends on the parameters describing the distribution of the connectivity
      matrix. In particular, we calculate the critical boundary in parameter space
      where the transition from ordered to chaotic dynamics takes place. Employing a
      recently developed framework for analyzing real-time computations, we show that
      only near the critical boundary can such networks perform complex computations on
      time series. Hence, this result strongly supports conjectures that dynamical
      systems that are capable of doing complex computational tasks should operate near
      the edge of chaos, that is, the transition from ordered to chaotic dynamics.

PMID- 15165397
TI  - Information geometry of U-Boost and Bregman divergence.
AB  - We aim at an extension of AdaBoost to U-Boost, in the paradigm to build a
      stronger classification machine from a set of weak learning machines. A geometric
      understanding of the Bregman divergence defined by a generic convex function U
      leads to the U-Boost method in the framework of information geometry extended to
      the space of the finite measures over a label set. We propose two versions of U
      Boost learning algorithms by taking account of whether the domain is restricted
      to the space of probability functions. In the sequential step, we observe that
      the two adjacent and the initial classifiers are associated with a right triangle
      in the scale via the Bregman divergence, called the Pythagorean relation. This
      leads to a mild convergence property of the U-Boost algorithm as seen in the
      expectation-maximization algorithm. Statistical discussions for consistency and
      robustness elucidate the properties of the U-Boost methods based on a stochastic
      assumption for training data.

PMID- 15165398
TI  - A new approach to the extraction of ANN rules and to their generalization
      capacity through GP.
AB  - Various techniques for the extraction of ANN rules have been used, but most of
      them have focused on certain types of networks and their training. There are very
      few methods that deal with ANN rule extraction as systems that are independent of
      their architecture, training, and internal distribution of weights, connections,
      and activation functions. This article proposes a methodology for the extraction
      of ANN rules, regardless of their architecture, and based on genetic programming.
      The strategy is based on the previous algorithm and aims at achieving the
      generalization capacity that is characteristic of ANNs by means of symbolic rules
      that are understandable to human beings.

PMID- 15165399
TI  - A classification paradigm for distributed vertically partitioned data.
AB  - In general, pattern classification algorithms assume that all the features are
      available during the construction of a classifier and its subsequent use. In many
      practical situations, data are recorded in different servers that are
      geographically apart, and each server observes features of local interest. The
      underlying infrastructure and other logistics (such as access control) in many
      cases do not permit continual synchronization. Each server thus has a partial
      view of the data in the sense that feature subsets (not necessarily disjoint) are
      available at each server. In this article, we present a classification algorithm
      for this distributed vertically partitioned data. We assume that local
      classifiers can be constructed based on the local partial views of the data
      available at each server. These local classifiers can be any one of the many
      standard classifiers (e.g., neural networks, decision tree, k nearest neighbor).
      Often these local classifiers are constructed to support decision making at each
      location, and our focus is not on these individual local classifiers. Rather, our
      focus is constructing a classifier that can use these local classifiers to
      achieve an error rate that is as close as possible to that of a classifier having
      access to the entire feature set. We empirically demonstrate the efficacy of the
      proposed algorithm and also provide theoretical results quantifying the loss that
      results as compared to the situation where the entire feature set is available to
      any single classifier.

PMID- 15165400
TI  - Diabetes mellitus, Ayurveda, and yoga.

PMID- 15165401
TI  - Methodological difficulties involving control groups in healing research:
      parallels between laying on of hands for the treatment of induced mammary cancers
      in mice to research in homeopathy.

PMID- 15165402
TI  - Acupuncture and the cycle of birth as viewed in an historic Japanese medical
      text.

PMID- 15165403
TI  - Identification of a p53-dependent pathway in the induction of apoptosis of human
      breast cancer cells by the natural product, resveratrol.
AB  - OBJECTIVE: Resveratrol, a constituent found in grapes and various other plants,
      has been shown to have chemo-preventive activity against cancer, and specifically
      demonstrated to induce apoptosis by p53-dependent pathways in murine cells. The
      goal of this research was to identify the role of p53-dependent or p53
      independent pathways in the induction of apoptosis in human breast cancer cells
      by this natural product. DESIGN: A number of human breast cancer cell lines, as
      well as a control of a wild-type line (astrocytoma N 1321N1), were investigated
      for induction of apoptosis by resveratrol using both microscopic evaluation and
      DNA fragmentation assays. Concurrently, we established the p53 gene status (wild
      type or mutant) of each cell line by Western blot using p53-specific antibody.
      RESULTS: Apoptosis induced by resveratrol was found to occur only in breast
      cancer cells expressing wild-type p53 but not in mutant p53-expressing cells.
      CONCLUSIONS: We therefore conclude that the natural product, resveratrol, induces
      apoptosis in breast cancer cells via p53-dependent pathways.

PMID- 15165404
TI  - Effects of Viscum album extract therapy in patients with cancer: relation with
      interleukin-6, soluble interleukin-6 receptor, and soluble gp130.
AB  - OBJECTIVES: The aim of this investigation was to determine the effects of Viscum
      album (VA) extract therapy on interleukin (IL)-12, IL-16, IL-6, soluble
      interleukin-6 receptor (sIL-6R), and soluble gp130 (sgp130) in patients with
      cancer. VA extract as immunomodulator is used as treatment either following or in
      combination with chemo/radiotherapy. Previously we showed that serum levels of IL
      12 and IL-16 were significantly elevated during tumor progression in 72 patients.
      The serum values of IL-6 were not significantly altered, however sIL-6R and
      sgp130 also increased significantly. DESIGN: In this study the serum levels of
      the five parameters were measured during VA extract therapy in 46 of these 72
      tumor patients and compared to the values before VA extract treatment. The levels
      of the serum parameters IL-12, IL-16, IL-6, sIL-6R, sgp130 were determined by
      enzyme-linked immunosorbent assay (ELISA). SETTING: Private cancer hospital in
      Arlesheim, Switzerland. RESULTS: Eighty percent (80%) of the tumor patients
      survived longer than 1 year (11 patients in stage I + II without, 8 patients
      after chemotherapy/radiotherapy, 10 patients in stage III + IV without, 8
      patients after chemotherapy). Clinically and with laboratory investigations there
      was no progression in these patients. VA extract therapy did not affect serum
      values of IL-12 or IL-16. However both the number of patients with increased
      levels of IL-6, sIL-6R, and sgp130 and also the serum values decreased
      significantly during the treatment, (between p < 0.05 and p < 0.001). In 20% of
      the patients with cancer with rapid progression who died within 3 months, the
      serum values of IL-6 increased significantly (p < 0.05), whereas the other
      investigated parameters did not change. CONCLUSION: The results show that
      measurements of IL-6, sIL-6R, and sgp130 could be important for establishing the
      clinical condition and evaluating treatment in tumor patients.

PMID- 15165405
TI  - Possible influence of infrasound on glioma cell response to chemotherapy: a pilot
      study.
AB  - OBJECTIVE: To assess the response of cultured human tumor cells to infrasound in
      combination with conventional anticancer agents using an infrasound-emitting
      apparatus marketed as a therapeutic device. DESIGN: Two pilot experiments
      measured proliferation of cultured brain tumor cells exposed to three treatment
      conditions: infrasound emission alone, infrasound in combination with the
      chemotherapy 5-fluorouracil (5-FU), and infrasound in combination with ionizing
      radiation. Results from each experimental condition were compared to those from
      appropriate control conditions. OUTCOME MEASURE: A standard colony-forming
      efficiency assay was used to assess tumor cell proliferation. RESULTS: Tumor cell
      proliferation was not significantly altered by treatment with infrasound alone,
      nor did infrasound appear to influence cellular response to x-rays. There was a
      significant interaction between 5-FU and infrasound (P < 0.0001), however,
      evident in decreased colony formation. CONCLUSION: Further research is warranted
      to assess potential synergism between infrasound and 5-FU against tumor cell
      proliferation, and to investigate the possible therapeutic use of infrasound.

PMID- 15165406
TI  - Low-frequency electromagnetic stimulation may lead to regression of Morris
      hepatoma in buffalo rats.
AB  - OBJECTIVE: The influence of low-frequency electromagnetic (LF-EM) waves on the
      processes of carcinogenesis and tumor growth has been the subject of experimental
      investigations for more than two decades and the results are promising. In
      parallel, an interesting method of complementary medicine, biophysical
      information therapy (BIT) or bioresonance therapy (BRT), which in principle is
      based on LF-EM stimulation, has emerged. BRT has been known since the late 1980s
      but is still poorly studied. The idea of applying BRT to tumors is based on two
      main premises: (1) endogenous biophotonic emission in the case of tumors is
      different from that produced by healthy tissues/cells and (2) BRT effects are
      believed to be primarily manifested at the immune-system level. Consequently, we
      decided to study the influence of BRT on a dynamic and well-known process: the
      expansion of transplantable hepatoma in rats. DESIGN: The study was carried out
      on female Buffalo rats with implanted Morris tumors (three experimental and one
      control group). Fourteen (14) consecutive in vivo exposures using a BRT device
      (BICOM B15, REGUMED Regulative Medizintechnik Gmbh, Graefelfing, Germany), were
      made from the third day after inoculation of the tumors. Biometric observations,
      intra vitam (tumor volume, growth ratio), were completed with histologic
      investigation (implantation locus, selected internal organs [lungs]). RESULTS:
      Thirty-one (31) cases (69%; n = 45) of total tumor regression were observed in
      experimental groups and these individuals were anesthetized to enable histologic
      verification to be made. No lung metastases--usually observed in tumor-bearers-
      could be detected. Moreover, in the inoculation loci, traces of former
      implantation and tumor absorption were found to be associated with high activity
      of cell-mediated immune response. No regressions were observed in the control
      group. CONCLUSIONS: We cannot exclude the possibility that LF-EM signals
      transmitted via BRT into the tumor-bearers may stimulate two separate processes:
      effective immunological response and/or tumor-cell death. The method appears to
      be capable of inducing the regression of transplantable hepatoma in vivo, thus is
      a potential subject of further studies.

PMID- 15165407
TI  - Effects of Hatha yoga and Omkar meditation on cardiorespiratory performance,
      psychologic profile, and melatonin secretion.
AB  - OBJECTIVES: To evaluate effects of Hatha yoga and Omkar meditation on
      cardiorespiratory performance, psychologic profile, and melatonin secretion.
      SUBJECTS AND METHODS: Thirty healthy men in the age group of 25-35 years
      volunteered for the study. They were randomly divided in two groups of 15 each.
      Group 1 subjects served as controls and performed body flexibility exercises for
      40 minutes and slow running for 20 minutes during morning hours and played games
      for 60 minutes during evening hours daily for 3 months. Group 2 subjects
      practiced selected yogic asanas (postures) for 45 minutes and pranayama for 15
      minutes during the morning, whereas during the evening hours these subjects
      performed preparatory yogic postures for 15 minutes, pranayama for 15 minutes,
      and meditation for 30 minutes daily, for 3 months. Orthostatic tolerance, heart
      rate, blood pressure, respiratory rate, dynamic lung function (such as forced
      vital capacity, forced expiratory volume in 1 second, forced expiratory volume
      percentage, peak expiratory flow rate, and maximum voluntary ventilation), and
      psychologic profile were measured before and after 3 months of yogic practices.
      Serial blood samples were drawn at various time intervals to study effects of
      these yogic practices and Omkar meditation on melatonin levels. RESULTS: Yogic
      practices for 3 months resulted in an improvement in cardiorespiratory
      performance and psychologic profile. The plasma melatonin also showed an increase
      after three months of yogic practices. The systolic blood pressure, diastolic
      blood pressure, mean arterial pressure, and orthostatic tolerance did not show
      any significant correlation with plasma melatonin. However, the maximum night
      time melatonin levels in yoga group showed a significant correlation (r = 0.71, p
      < 0.05) with well-being score. CONCLUSION: These observations suggest that yogic
      practices can be used as psychophysiologic stimuli to increase endogenous
      secretion of melatonin, which, in turn, might be responsible for improved sense
      of well-being.

PMID- 15165408
TI  - Individual differences in response to randomly assigned active individualized
      homeopathic and placebo treatment in fibromyalgia: implications of a double
      blinded optional crossover design.
AB  - OBJECTIVE: To assess individual difference characteristics of subgroups of
      patients with fibromyalgia (FM) patients with respect to the decision to stay in
      or switch from randomly-assigned verum or placebo treatment during an optional
      crossover phase of a double-blinded homeopathy study. DESIGN: Double-blinded,
      randomized, placebo-controlled, optional crossover clinical trial. PARTICIPANTS:
      Fifty-three (53) community-recruited patients with FM entered the optional
      crossover phase. INTERVENTION: Two homeopaths jointly selected an individualized
      homeopathic remedy for all patients. The pharmacy dispensed either verum LM
      remedy or indistinguishable placebo in accord with randomized assignment for 4
      months and the patient's optional crossover decision for an additional 2 months.
      OUTCOME MEASURES: Patients completed a battery of baseline state/trait
      questionnaires, including mood, childhood neglect and abuse, and trait
      absorption. They rated global health (whole person-centered) and tender point
      pain on physical examination (disease-specific) at baseline, 3 months, and 6
      months. RESULTS: Rates of optional crossover from verum to placebo or placebo to
      verum were comparable (p = 0.6; 31%, and 41%, respectively). The switch subgroups
      had greater baseline psychologic issues (emotional neglect in placebo-switch;
      depression and anger in verum-switch). The verum-stay subgroup scored highest on
      treatment helpfulness and included all six exceptional responders who fell, prior
      to crossover, into the top terciles for improvement in both global health and
      pain. Patients staying in their randomly assigned groups, active or placebo (n =
      34), scored significantly higher in trait absorption than did those who switched
      groups (n = 19). CONCLUSION: Individual difference factors may predict better and
      poorer responders with FM to specific and nonspecific effects of homeopathic and
      placebo treatment.

PMID- 15165409
TI  - Electroencephalographic cordance patterns distinguish exceptional clinical
      responders with fibromyalgia to individualized homeopathic medicines.
AB  - OBJECTIVES: To characterize initial central nervous system responses to olfactory
      administration of homeopathic remedies as biomarkers for subsequently
      exceptional, simillimum-like clinical outcomes at a systemic level (i.e., both
      locally and globally). DESIGN: Double-blinded, randomized, placebo-controlled
      clinical trial. SETTING: A private homeopathic clinic in Phoenix, AZ, and a
      university laboratory in Tucson, AZ. PATIENTS: Sixty-two (62) persons with
      physician-confirmed fibromyalgia (FM) (mean age, 49 years; 94% women) enrolled;
      53 completed the 3-month assessment visit. Exceptional responders (n = 6, 23% of
      active treatment group; none on placebo) were those with improvements in the top
      one-third for both tender point pain and global health ratings after 3 months.
      INTERVENTION: Patients took daily oral doses of treatment solution in LM
      (1/50,000 dilution) potency (active group received individualized remedy; placebo
      group received plain solvent). Dependent measures: Baseline and 3-month
      difference scores for initial prefrontal electroencephalographic alpha frequency
      cordance (EEG-C, a correlate of functional brain activity) during 16 pairs of
      randomized, double-blinded bottle sniffs (treatment minus control solutions).
      RESULTS: Exceptional responders versus other patients exhibited significantly
      more negative initial EEG-C difference scores at prefrontal sites. Right
      prefrontal cordance findings correlated with subsequently reduced pain (r = 0.85,
      p = 0.03), better global health (r =-0.73, p = 0.10), and trait absorption
      (genetically determined ability to focus attention selectively and fully) (r =
      0.91, p = 0.012). CONCLUSIONS: These observations suggest prefrontal EEG-C as an
      early biomarker of individualized homeopathic medicine effects in patients with
      FM who later exhibit exceptional outcomes. Prefrontal cortex controls executive
      function, including ability to redirect attention. Interactions between executive
      function, absorption, and the simillimum remedy could facilitate exceptional
      responses.

PMID- 15165410
TI  - Toward general experimentation and discovery in conditioned laboratory spaces:
      Part II. pH-change experience at four remote sites, 1 year later.
AB  - OBJECTIVES: (1) To demonstrate information entanglement between separated sites
      of a single experimental system over distances of 1500-2000 miles and (2) to
      provide experimental DeltapH(t)-data, above the theoretical value for conditioned
      spaces, over a long time period for these various sites. DESIGN: The same as Part
      I of this series but with two additional control sites, 1500-2000 miles distant
      from any intention imprinted electrical device (IIED) site. SETTING/LOCATION: The
      same as Part I but scientific laboratories for the two additional control sites.
      SUBJECTS: Three IIED sites plus five control sites. INTERVENTIONS: None. RESULTS:
      DeltapH(t)-data variations with time, over a long time duration, for all sites.
      CONCLUSIONS: Major information entanglement exists between IIED sites and non
      IIED sites, even at separation distances in excess of 2000 miles.

PMID- 15165411
TI  - Electroencephalographic evidence of correlated event-related signals between the
      brains of spatially and sensory isolated human subjects.
AB  - OBJECTIVE: To determine whether correlated event-related potentials (ERPs) can be
      detected between the brains of spatially and sensory isolated human subjects.
      DESIGN AND SETTING: Simultaneous digitized electroencephalograms (EEGs) were
      recorded from the occipital area in pairs of human subjects placed in sound
      attenuated rooms separated by 10 meters. One person relaxed in one of the rooms
      while the other received visual stimulation while in the other room. Prior to
      each experiment, members of the pair were randomly designated as sender and
      receiver. Sessions were subsequently repeated with subjects reversing their
      roles. Previous to each session, the sender was instructed "to attempt sending an
      image/thought." The receiver was instructed "to remain open to receive any
      image/thought from his/her partner." Alternating stimulus-on/stimulus-off
      conditions were presented throughout the session to the sender, while a stimulus
      off condition was presented to the receiver. SUBJECTS: Thirty-seven (37) female,
      and 23 male subjects (n = 60; 30 pairs) participated in the study. Subjects knew
      each other well and claimed to have previous experience of being
      emotionally/psychologically connected to one another. OUTCOME MEASURES: A Runs
      test was applied to compare EEG "hits" in the receiver's EEG during the sender'
      stimulus-on condition versus sender's stimulus-off conditions. Test results at p
      < 0.01 were considered evidence of correlated brain signals. Pairs in whom at
      least one member had significant results were invited back for replication.
      RESULTS: Of the 60 subjects tested, 5 (4 women/1 man) showed significantly higher
      brain activation (p < 0.01) during their sending partner's stimulus-on condition
      as compared to stimulus-off condition. Using the Stouffer z meta-analytic method
      all receiver EEG results across all 60 subjects were combined by transforming the
      individual session p values into z scores. Data analyses showed overall
      significant results for EEG data recorded during the flickering condition (z =
      3.28, p = 0.0005) as well as nonsignificant results for data recorded during the
      static condition (z = 0.35, p = 0.64). Four pairs participated in a replication
      experiment during which one pair replicated the effect. CONCLUSIONS: These
      results indicate that in some pairs of human subjects a signal may be detected in
      the brain of a distant member of the pair when the brain of the other member is
      visually stimulated. These data support the findings of similar studies performed
      in seven laboratories reported in the peer-reviewed literature since 1963.
      Research in this area should now proceed with investigation of its physical and
      biologic mechanism, its generalizability to varying populations and
      relationships, and its clinical application.

PMID- 15165412
TI  - Event-related electroencephalographic correlations between isolated human
      subjects.
AB  - OBJECTIVE: To examine electroencephalograms (EEG) in pairs of people to see if
      event-related potentials evoked in one person's brain are correlated with
      concurrent responses in the brain of a distant, isolated person. DESIGN:
      Simultaneously record EEGs using independent physiologic monitoring systems. One
      person relaxes in a double steel-walled, electromagnetically and acoustically
      shielded room while a second, located in a dimly lit room 20 meters away, is
      stimulated at random times by the live video image of the first person. SUBJECTS:
      Thirteen (13) pairs of volunteers. Eleven (11) pairs of adult friends and 2
      mother-daughter pairs. OUTCOME MEASURES: Epochs of interest were the moments of
      stimulus onset and offset, +/- 5 seconds, in both participants' EEGs. A positive
      correlation was postulated to appear between the ensemble variance of the
      stimulated subjects' EEGs versus an identical measure in the nonstimulated
      subjects. Control data using the same equipment and test conditions, but without
      humans present, was collected to check for equipment and analytical artifacts.
      Nonparametric bootstrap methods were used to assess statistical significance of
      the observed correlations. RESULTS: The control test resulted in a correlation of
      r =-0.03, p = 0.61; the experimental test resulted in r = 0.20, p = 0.0005. Three
      (3) of the 13 pairs of participants showed independently significant
      correlations. Examination of the stimulated subjects' event-related potentials
      showed that the stronger their responses, the larger the corresponding responses
      in the nonstimulated subjects (p = 0.0008). CONCLUSION: Under certain conditions,
      the EEG of a sensorially isolated human subject can become correlated with event
      related potentials in a distant person's EEG. This suggests the presence of an
      unknown form of energetic or informational interaction.

PMID- 15165413
TI  - Electrophysiological evidence of intuition: Part 2. A system-wide process?
AB  - OBJECTIVES: This study aims to contribute to a scientific understanding of
      intuition, a process by which information normally outside the range of conscious
      awareness is perceived by the body's psychophysiological systems. The first
      objective, presented in two empirical reports (Part 1 and Part 2), was to
      replicate and extend the results of previous experiments demonstrating that the
      body can respond to an emotionally arousing stimulus seconds before it is
      actually experienced. The second objective, to be presented in a forthcoming
      publication (Part 3), is to develop a theory that explains how the body receives
      and processes information involved in intuitive perception. DESIGN: The study
      used a counterbalanced crossover design, in which 30 calm and 15 emotionally
      arousing pictures were presented to 26 participants under two experimental
      conditions: a baseline condition of "normal" psychophysiologic function and a
      condition of physiological coherence. Primary measures included: skin
      conductance; the electroencephalogram (EEG), from which cortical event-related
      potentials (ERP) and heartbeatevoked potentials (HBEP) were derived; and the
      electrocardiogram (ECG), from which cardiac decelerations/ accelerations were
      derived. These measures were used to investigate where and when in the brain and
      body intuitive information is processed. RESULTS: The main findings presented
      here are: (1) surprisingly, both the heart and brain appear to receive and
      respond to intuitive information; (2) even more surprisingly, there is compelling
      evidence that the heart appears to receive intuitive information before the
      brain; (3) there were significant differences in prestimulus ERPs for calm versus
      emotional stimuli; (4) the frontal cortex, temporal, occipital, and parietal
      areas appear to be involved in the processing of prestimulus information; (5)
      there were significant differences in prestimulus calm/emotional HBEPs, primarily
      in the coherent mode; (6) there were significant gender differences in the
      processing of prestimulus information. Especially noteworthy is the apparent
      interaction between the HBEPs and ERPs in the females, which suggests that the
      heart modulates the ERP and that females are more attuned to intuitive
      information from the heart. CONCLUSIONS: Overall, our data suggest that the heart
      and brain, together, are involved in receiving, processing, and decoding
      intuitive information. On the basis of these results and those of other research,
      it would thus appear that intuitive perception is a system-wide process in which
      both the heart and brain (and possibly other bodily systems) play a critical
      role. To account for the study's results, Part 3 will develop a theory based on
      holographic principles explaining how intuitive perception accesses a field of
      energy into which information about "future" events is spectrally enfolded.

PMID- 15165414
TI  - Germane facts about germanium sesquioxide: I. Chemistry and anticancer
      properties.
AB  - This paper reviews the history, chemistry, safety, toxicity, and anticancer
      effects of the organogermanium compound bis (2-carboxyethylgermanium) sesquioxide
      (CEGS). A companion review follows, discussing the inaccuracies in the scientific
      record that have prematurely terminated research on clinical uses of CEGS. CEGS
      is a unique organogermanium compound first made by Mironov and coworkers in
      Russia and, shortly thereafter, popularized by Asai and his colleagues in Japan.
      Low concentrations of germanium occur in nearly all soils, plants and animal
      life; natural occurrence of the CEGS form is postulated but not yet demonstrated.
      The literature demonstrating its anticancer effect is particularly strong: CEGS
      induces interferon-gamma (IFN-gamma), enhances natural killer cell activity, and
      inhibits tumor and metastatic growth--effects often detectable after a single
      oral dose. In addition, oral consumption of CEGS is readily assimilated and
      rapidly cleared from the body without evidence of toxicity. Given these findings,
      the absence of human clinical trials of CEGS is unexpected. Possible explanations
      of why the convincing findings from animal research have not been used to support
      clinical trials are discussed. Clinical trials on CEGS are recommended.

PMID- 15165415
TI  - Germane facts about germanium sesquioxide: II. Scientific error and
      misrepresentation.
AB  - The preceding paper reviewed the anticancer properties and safety of bis (2
      carboxyethylgermanium) sesquioxide (CEGS). An examination of those data leads one
      to question why this information has not stimulated clinical trials in patients
      with cancer. The answer is discussed in this paper, which traces the history to
      an error published in the scientific literature in 1987. The reliance by
      subsequent authors on secondary sources, citing only the error and not the
      correction published in 1988, constitutes part of the explanation of why CEGS has
      been neglected. A second factor is also considered: careless reporting about any
      germanium-based compound as if the many thousands of germanium compounds were all
      the same. This combination of a publication error, careless writing, and the
      reliance on secondary sources appears to be responsible for the neglect of the
      potential clinical use of this unique germanium compound.

PMID- 15165416
TI  - Wellness lifestyles I: A theoretical framework linking wellness, health
      lifestyles, and complementary and alternative medicine.
AB  - Scholarship concerning complementary and alternative medicine (CAM) practices
      within the United States could benefit from incorporating sociological
      perspectives into the development of a comprehensive research agenda. We review
      the literature on health and wellness emphasizing definitions and distinctions,
      the health lifestyles literature emphasizing issues of both life choices and life
      chances, and studies of CAM suggesting utilization as an aspect of a wellness
      lifestyle. This review forms the foundation of a new theoretical framework for
      CAM research based on the interrelationship of CAM with health promotion,
      wellness, and health lifestyles. To date, few studies have sought to bring these
      various elements together into a single, comprehensive model that would enable an
      assessment of the complexity of individual health and wellness in the context of
      CAM. We argue that attention to literatures on health measurement and health
      lifestyles are essential for exploring the effectiveness and continuing use of
      CAM.

PMID- 15165417
TI  - Wellness lifestyles II: Modeling the dynamic of wellness, health lifestyle
      practices, and Network Spinal Analysis.
AB  - OBJECTIVE: Empirical application of a theoretical framework linking use of
      Network Spinal Analysis (NSA; a holistic, wellness-oriented form of complementary
      and alternative medicine [CAM]), health lifestyle practices, and self-reported
      health and wellness. DESIGN: Cross-sectional self-administered survey study.
      RESPONDENTS: Two thousand five hundred and ninety-six (2596) patients from 156
      offices of doctors who were members of the Association for Network Chiropractic
      (currently titled Association for Network Care); estimated response rate was 69%.
      MEASURES: Exogenous variables entered into the structural equation model include
      gender, age, education, income, marital status, ailments, life change, and
      trauma. A wellness construct consisted of calculated difference scores between
      two referents, "presently" and "before Network" care, for self-reported items
      representing wellness domains of physical state, mental-emotional state, stress
      evaluation, and life enjoyment. Positive reported change in nine items assembled
      into dietary practices, health practices, and health risk dimensions serve as
      indicators of the construct of changes in health lifestyle practices. The NSA
      care construct consisted of duration of care in months, awareness of energy and
      awareness of breathing since beginning Network care. RESULTS: Of the exogenous
      variables only gender, age, and education remain in the final parsimonious
      structural equation model in these data. Reported wellness benefits accrue to
      individuals along a direct path from both self-reported positive lifestyle change
      (0.22), and from NSA care (0.43). The path (0.65) from NSA care to positive
      health lifestyle changes indicates that NSA care also has an indirect effect on
      wellness through changes in health lifestyle practices. CONCLUSIONS: The
      Structural Equation model tested in these analyses lends support to our
      theoretical framework linking wellness, health lifestyles, and CAM. This study
      provides further evidence that our measurements of health and wellness are
      particularly appropriate for investigating wellness-oriented CAM. There is a
      positive relationship between the experience of NSA care and self-reported
      improvements in wellness as well as self-reported changes in lifestyle practices.
      NSA care users tend toward the practice of a positive health lifestyle, which
      also has a direct effect on reported improvements in wellness. These empirical
      links are discussed relative to the sociodemographic characteristics of this
      population and show that use of NSA care is an aspect of a wellness lifestyle.

PMID- 15165418
TI  - Role of selected Indian plants in management of type 2 diabetes: a review.
AB  - Type 2 diabetes has become a global epidemic. Modern medicines, despite offering
      a variety of effective treatment options, can have several adverse effects.
      Ayurveda, a science that uses herbal medicines extensively, originated in India.
      Of considerable interest is the adoption of Ayurveda by the mainstream medical
      system in some European countries (e.g., Hungary), emphasizing this modality is
      increasing worldwide recognition. From ancient times, some of these herbal
      preparations have been used in the treatment of diabetes. This paper reviews the
      accumulated literature for 10 Indian herbs that have antidiabetic activity and
      that have been scientifically tested. Few of these herbs, such as Momordica
      charantia, Pterocarpus marsupium, and Trigonella foenum greacum, have been
      reported to be beneficial for treating type 2 diabetes. Mechanisms such as the
      stimulating or regenerating effect on beta cells or extrapancreatic effects are
      proposed for the hypoglycemic action of these herbs.

PMID- 15165419
TI  - How informed is consent in sham-controlled trials of acupuncture?
AB  - OBJECTIVES: We sought to investigate whether, and if so, how published sham
      controlled trials of acupuncture report on the information given to patients
      about true and sham interventions. We asked acupuncture therapists to provide
      original patient information leaflets in order to study how interventions were
      described in more detail. METHODS: Forty-seven (47) published sham-controlled
      trials of acupuncture collected for a systematic review on sham techniques were
      screened to determine whether they reported on information given to patients
      about study interventions; any such information was extracted. We contacted
      authors of published studies and other researchers in the field and asked them to
      provide copies of original patient information leaflets. Information given to
      patients about true and sham interventions was extracted. RESULTS: Ten (10; 21%)
      of the 47 published studies included some information on how patients were
      informed. None of these studies appear to have used the term "sham" or "placebo"
      and most appear to have suggested that two types of acupuncture were compared. In
      the 16 original patient information leaflets obtained, the way patients were
      informed varied greatly: 7 leaflets explicitly included words such as "sham,"
      "placebo," or "dummy." Others described the control intervention as not meeting
      all criteria of acupuncture. Finally, one group of studies simply suggested that
      different types of acupuncture were being compared. CONCLUSION: Our results
      indicate that (1) only a minority of published trials report on information given
      to patients about true and sham interventions and (2) that information strategies
      vary considerably and are often not fully explicit. This has not only ethical
      relevance but also might influence results of trials.

PMID- 15165421
TI  - Yin scores and yang scores: A new method for quantitative diagnostic evaluation
      in traditional Chinese medicine research.
AB  - OBJECTIVE: To develop and evaluate a method for quantitative evaluation of yin
      and yang (yin and yang scores) in human subjects for the purposes of research.
      This method aims to classify subjects into groups allowing future quantitative
      testing of key research questions such as: do different groups of patients
      respond differently to acupuncture treatments or Chinese herb formulas? METHODS:
      In a pilot study of inter-rater reliability, 12 volunteers were each successively
      interviewed and examined by 6 acupuncturists on the same day. Each acupuncturist
      gave each volunteer a score for yin and a score for yang on a scale of -10 to
      +10, zero representing a "balanced" score. Acupuncturists were blinded to each
      other's scores. RESULTS: Overall mean (+/-standard deviation [SD]) yin and yang
      scores were -1.86 +/- 0.90 and -0.68 +/- 1.23 respectively. Intraclass
      correlations (ICCs) associated with a single acupuncturist's ratings were 0.35
      (yin) and 0.36 (yang). ICC's for subject's mean scores based on the six
      acupuncturists were 0.77 (yin) and 0.78 (yang). Significant differences in mean
      scores across subjects were detected for yin (p < 0.001) and yang (p < 0.001)
      (repeated-measures analysis of variance [ANOVA]) based on the multiple
      acupuncturists' ratings. CONCLUSION: These results indicate that (1) yin and yang
      can be quantified in a reliable manner, but evaluation by multiple acupuncturists
      is necessary to obtain a reliable score; (2) yin and yang scores can be used to
      group individuals for the purposes of statistical analysis. Further evaluation of
      yin and yang scores in a greater number and wider variety of patients will be
      needed to evaluate the potential usefulness of this measurement tool in
      acupuncture clinical trials and basic physiologic research.

PMID- 15165423
TI  - Medical models. Cultural, historical and terminology issues.

PMID- 15165422
TI  - A pilot study of a Kampo formula, EH0202, with intriguing results for menopausal
      symptoms.
AB  - OBJECTIVES: To investigate the effects of EH0202, a Japanese herbal supplement,
      on the immune and endocrine systems in women with menopausal symptoms. DESIGN AND
      SUBJECTS: Thirty-two (32) postmenopausal women (53.0 +/- 5.1 years old)
      presenting with menopausal complaints were enrolled in a clinical study. Patients
      were given an herbal supplement, EH0202 (6 g per day for 6 months) and were
      assessed for reduction of their overall symptoms using Greene's Climacteric Scale
      and Visual Analog Scale. Plasma interleukin-6 (IL-6), soluble IL-6 receptor,
      tumor necrosis factor-alpha, granulocyte macrophage-colony stimulating factor (GM
      CSF), granulocyte-colony stimulating factor, follicle-stimulating hormone (FSH),
      and luteinizing hormone concentrations were measured before and 6 months after
      EH0202 administration. RESULTS: There was a significant decrease in the
      climacteric scale score (p = 0.0007) and visual analogue scale (p < 0.0001) after
      6 months of EH0202 treatment. There was significant increase (p = 0.0097) in
      plasma GM-CSF levels and a significant decrease (p = 0.018) in plasma FSH levels
      after 6 months of EH0202 administration. CONCLUSIONS: EH0202 (MACH) decreased the
      plasma FSH level and stimulated myelopoiesis through the cytokine system, thereby
      clinically reduced menopausal symptoms in postmenopausal women. Therefore, in
      postmenopausal women, this product probably acts as an immunomodulator and
      endocrine modulator.

PMID- 15165424
TI  - Bringing holism into mainstream biomedical education.
AB  - Introducing holism and complementary medicine into mainstream medical education
      provides many scientific, philosophical, and personal challenges. The growth of
      new knowledge always necessitates venturing into areas, which are, by definition,
      unknown, hence arise potential clashes of ideology, knowledge, evidence,
      interpretation, language, and personality. This paper outlines some of the
      experience and progress made at Monash University Victoria, Australia, in
      teaching this material in undergraduate medical education. The Monash medical
      course has always been known for its commitment to an integrated curriculum, a
      holistic perspective, and the personal development of its students. Some of the
      points of integration in the core curriculum already achieved include health
      enhancement and mindfulness-based stress management programs right from first
      year, lectures and forums on complementary medicine, integration of this material
      into weekly case-based teaching, and health promotion and mind-body medicine. For
      very interested students, electives provide an opportunity to explore subjects in
      more depth. Experience has taught us that it is as important to learn how to
      deliver the message as it is to refine its content. This presents challenges that
      are as much personal as they are intellectual. Areas of particular importance are
      the academic environment, language, diplomacy, style, relevance, and evidence. In
      this process, building relationships, collegiality, patience, objectivity,
      impartiality, and humor are helpful.

PMID- 15165425
TI  - Standards of education, regulation, and market control: perspectives on
      complementary and alternative medicine in Ontario, Canada.
AB  - This paper provides a contemporary analysis of the issues and questions
      surrounding the regulation and standardization of education with respect to two
      complementary and alternative medicine (CAM) professions, namely Chinese
      traditional medicine and homeopath in Ontario, Canada. Rather than taking a
      standard of education for granted, the assumption that standardizing professional
      education is a positive move is critiqued because it is claimed to ensure public
      safety and uniformity within the profession. It is argued that such an assumption
      fails to deconstruct the power relations involved with setting a standard of
      education and continues to ignore the fact that setting a standard of education
      in CAM is part and parcel of biomedical dominance, competition, turf wars and
      survival. At the end of this paper, some critical questions regarding setting
      standards of education by the health professions in general are raised.

PMID- 15165426
TI  - The future of complementary and alternative medicine--models of integration.
AB  - The current definitions of complementary and alternative medicine (CAM) and
      orthodoxy are culturally and politically determined. They obscure the debate
      about holism and integrative care and they give therapies and therapists
      precedence over patients in the design of health care systems. This paper
      considers three current models of delivery of CAM and biomedical care in the
      world. These models are the market model, the regulated model, and the
      assimilated model. Each of these models is described and consideration is given
      to likely futures for each of them. A fourth model, the patient centered model is
      proposed, which shifts the power from therapists to patients and regulates
      products and services irrespective of CAM or biomedical definitions. Only this
      latter model is presented as the one likely to support the development of truly
      integrated medicine, explicitly for the benefit of patients rather than
      therapists or industries.

PMID- 15165430
TI  - Autism and learning disability.
AB  - In this article a short overview is given of the relationship between autism and
      learning disability. Autism exists with any level of intelligence, but many
      individuals with autism suffer also from learning disability. Although both
      disorders show overlap in some behaviours they are different in many aspects. Are
      they distinct syndromes which influence each other, or do they belong to a broad
      spectrum of a condition?

PMID- 15165432
TI  - Autism in Angelman syndrome: an exploration of comorbidity.
AB  - The aim was to explore the comorbidity between Angelman syndrome and autism
      spectrum disorders (ASDs). Identification of autism in children with Angelman
      syndrome presents a diagnostic challenge. In the present study, 16 children with
      Angelman syndrome, all with a 15q11-13 deletion, were examined for ASDs. Thirteen
      children with Angelman syndrome received an ADOS-G algorithm classification of
      ASD; the remaining three were outside the autistic spectrum. Ten fulfilled the
      criteria for autism, and three for PDD-NOS. The 10 children with Angelman
      syndrome and comorbid autism were compared with eight children with only autism
      regarding their social and communicative skills. The results indicated that
      Angelman syndrome is better understood in terms of developmental delay, and
      autism in terms of developmental deviance. It is concluded that autism might have
      been overdiagnosed due to the extremely low mental age of the children with
      Angelman syndrome.

PMID- 15165431
TI  - Chromosomal anomalies in individuals with autism: a strategy towards the
      identification of genes involved in autism.
AB  - We review the different strategies currently used to try to identify
      susceptibility genes for idiopathic autism. Although identification of genes is
      usually straightforward in Mendelian disorders, it has proved to be much more
      difficult to establish in polygenic disorders like autism. Neither genome screens
      of affected siblings nor the large number of association studies using candidate
      genes have resulted in finding autism susceptibility genes. We focus on the
      alternative approach of 'positional cloning' through chromosomal aberrations in
      individuals with autism. In particular, balanced aberrations such as reciprocal
      translocations or inversions offer a unique opportunity, since only the genes in
      the breakpoint regions are candidate genes. This approach, in combination with
      others, is likely to produce results in the coming years.

PMID- 15165433
TI  - Using the social communication questionnaire to identify 'autistic spectrum'
      disorders associated with other genetic conditions: findings from a study of
      individuals with Cohen syndrome.

PMID- 15165434
TI  - Catatonia and autistic spectrum disorders.
AB  - The phenomenon of catatonic-like states in people with autistic spectrum
      disorders is discussed in the context of current knowledge about catatonia as it
      occurs in severe mental illness and, less frequently documented, in conjunction
      with developmental disorders. The existing literature on catatonic-like states in
      people with autistic spectrum disorders is summarized, and it is suggested that
      such states are not directly comparable with the existing concepts of catatonia.
      A concept of 'autistic catatonia' is outlined in terms of both its phenomenology
      and its possible aetiological and maintaining factors. A case study is presented
      that examines this phenomenon from a cognitive neuropsychological perspective,
      together with implications for everyday management. The implications of this work
      for both research and clinical practice are discussed.

PMID- 15165435
TI  - Making sense in a fragmentary world: communication in people with autism and
      learning disability.
AB  - The communicative capabilities of people with autism are impaired and limited in
      significant ways. The problems are characterized by a lack of intentionality and
      symbol formation, which indicates that the deviant development of communication
      in autism is associated with a specific cognitive style. The central coherence
      theory can offer insight into the specific communication problems of people with
      autism, since a weaker drive for central coherence leads to problems in sense
      making and, consequently, in communication. In the case of the comorbidity of
      autism and learning disability, the communication problems are aggravated. The
      crucial point is the determination of the level of sense-making, taking this
      comorbidity into account. Assessment and intervention have to be tuned to
      individual needs, in order to increase the communicative competence of people
      with autism and learning disability.

PMID- 15165436
TI  - Videoconferencing in family therapy: a review.
AB  - Videoconferencing is used in psychiatry for various purposes. There is a need for
      research on videoconferencing in family therapy, as there are hardly any reports
      on the topic: in a literature search, we found only four references to family
      therapy and videoconferencing. In the Department of Psychiatry at Oulu University
      Hospital, the use of videoconferencing has steadily increased over the last few
      years, and in 2002 the equipment was used for 600 hours, of which 84 hours (14%)
      involved consultation and 12 hours (2%) family therapy. We postulate that the use
      of videoconferencing for family therapy will incur various restrictions, but may
      also open up new opportunities. Videoconferencing may allow people in remote
      regions to benefit from family therapy services. Using modern equipment, it is
      possible to attain television broadcast quality in a videoconference, but we do
      not know the effect of videoconferenced delivery on the outcome of therapy. It
      will therefore be important to collect systematic data on family therapy
      delivered via videoconference.

PMID- 15165437
TI  - Feasibility of neuropsychological testing of older adults via videoconference:
      implications for assessing the capacity for independent living.
AB  - We examined the feasibility of administering neuropsychological tests via
      videoconference. Twenty-nine participants from central Alberta volunteered for
      the study. All were 60 years of age or older and were without neurological or
      psychiatric disturbance. All the participants were tested under two experimental
      conditions: face to face and via videoconference (at a bandwidth of 336 or 384
      kbit/s). Memory and learning, letter fluency, expressive word knowledge,
      reasoning, verbal attention and visual-spatial processing were examined. Scores
      for expressive word knowledge were similar in the two test conditions, although
      larger differences were found in the visual-spatial processing scores. Following
      the final testing session, participants were given a questionnaire which explored
      their reactions to the technology. There was no significant difference in the
      proportions of participants who expressed a preference for each mode of testing.
      All participants were comfortable with the technology.

PMID- 15165438
TI  - Neurosurgical teleconsultations in northern Norway.
AB  - We carried out a prospective study of the effect of neurosurgical
      teleconsultations on patient management in northern Norway. The total number of
      teleradiology image transfers during an eight-month study period was 723. We
      recorded data on 99 (14%) of these teleconsultations, which concerned 92
      patients; the remainder were transfers to other departments at our hospital and
      transfers of routine examinations from a small community hospital that did not
      have a radiologist. The neurosurgeon on call noted the clinical condition and
      response time for each consultation. The consequences of the teleconsultation and
      the eventual benefits of the image transfer were evaluated. All 10 referring
      hospitals in the region used the service. The median response time was 3 hours
      (range 1-21 hours) in emergency cases and 1 day (range 1-7 days) in ordinary
      consultations. The response time was significantly shorter for patients with head
      injuries (median 3 hours) than for those with intracranial tumours (median 24
      hours). Image transfer was considered beneficial for the patient in 93% of the
      cases. Avoidance of unnecessary patient transfer, changes of treatment at the
      referring hospital on the advice of the neurosurgeon and initiation of emergency
      transfer occurred in 34%, 42% and 13% of cases, respectively. The results confirm
      that teleconsultations between referring hospitals and a regional neurosurgical
      service influence patient management and reduce the frequency of patient
      transfer.

PMID- 15165440
TI  - A telemedicine system for collaborative work on radiographic coronary video
      images.
AB  - We designed a telemedicine system that supports collaborative work on video
      images from coronary cine-angiograms and cine-ventriculograms. Two workstations
      were connected by ISDN at 128 kbit/s. Coronary cine-angiogram and cine
      ventriculogram video-images were transmitted to an image examination workstation
      before the images were required for analysis (i.e. in a 'pre-fetch' operation).
      If one workstation changed even a single frame in a video-sequence, then the
      change was transmitted to the other workstation, rather than the entire video
      sequence. To evaluate the performance of the system, the diagnoses made by five
      cardiology specialists were compared with those recorded in the original report.
      Coronary cine-angiogram and cine-ventriculogram video-images from 27 patients
      were used. The cardiologists, who were blinded to the patient information,
      regenerated the video-images on the workstation and assessed coronary arterial
      stenosis and wall motion. The kappa scores for clinician agreement with the
      original reports for ratings of stenosis were 0.54-0.66 and for wall motion were
      0.41-0.69. The system performed reasonably reliably and it therefore appears
      likely to be useful in telemedicine work.

PMID- 15165439
TI  - A pilot study of long-term monitoring of human movements in the home using
      accelerometry.
AB  - We assessed the feasibility of using a waist-mounted, wireless triaxial
      accelerometer (TA) to monitor human movements in an unsupervised home setting to
      detect changes in functional status. A pilot study was carried out with six
      healthy subjects aged 80-86 years. The subjects wore a TA unit every day for two
      to three months. Each morning they carried out a short routine of directed
      movements that included standing, sitting, lying and walking. Important movement
      variables were measured. During the rest of the day, subjects were monitored for
      falls, and variables such as metabolic energy expenditure were measured. All
      subjects remained healthy; there was no overall change in functional status and
      there were only slight fluctuations in health status. No longitudinal changes
      were detected in any of the variables measured during the directed routine. There
      was a moderate correlation between weekly self-reported health status and energy
      expenditure: subjects reported a lower health status for weeks in which they
      expended less energy. The TA system was found to be practical for long-term,
      unsupervised home monitoring. All subjects found the system simple to use and the
      TA unit unobtrusive and comfortable to wear. High compliance rates were achieved:
      the TA units were worn on 88% of the days in the study, for an average of 11.2
      hours per day.

PMID- 15165441
TI  - Nurse and patient communication via low- and high-bandwidth home telecare
      systems.
AB  - We examined nurse-patient communication on two videoconferencing systems: a video
      phone (PSTN video) and a PC-based system (IP video). The former used data
      transmission via a modem at 33.6 kbit/s and the latter via a local-area network
      at up to 512 kbit/s. Twenty-six nurses and 18 volunteers (simulated patients)
      participated. On each video system nurse-patient dyads completed scripted
      interactions; they then completed questionnaires to assess communication. Of the
      participants, 84% (n=37) preferred IP video and 14% (n=6) preferred PSTN video
      (one expressed no preference). IP video was rated significantly higher in all
      communication quality areas except self-consciousness/embarrassment. Although
      participants' overall ratings were higher for the IP video system, two important
      advantages of the PSTN video system were identified by both nurses and patients:
      first, it provided superior visualization of the medication bottle, insulin
      syringe and the patient's skin; and second, it was easier to use. Video quality
      and audio quality are important determinants of patient and provider perceptions,
      but ease of use, clinical appropriateness, and the need for training and support
      must not be forgotten.

PMID- 15165442
TI  - The status of telepsychiatry services in Canada: a national survey.
AB  - A survey of Canadian telepsychiatry programmes was undertaken to provide
      information for future health services. Fourteen programmes were identified. They
      used a variety of service models and administrative arrangements. The average
      number of clinical consultations per programme per year was 238, which
      corresponds to 107 psychiatric teleconsultations per million persons served by
      the programmes. The rate for children's telepsychiatry services was higher, at
      194 per million. Comparison with some telepsychiatry programmes in the USA
      revealed similar patterns of activity. While the development of telepsychiatry
      services in Canada is promising, there is nevertheless concern regarding the
      viability and activity levels of these programmes over the long term. This survey
      demonstrates that programmes from across a large country can respond to a
      standardized questionnaire and provide comparable information.

PMID- 15165443
TI  - Designing a framework for the evaluation of paediatric telepsychiatry: a
      participatory approach.
AB  - While there is a great deal of interest in evaluating participants' experiences
      of teleconsultation programmes, specific frameworks for such evaluations are
      scarce. We have conducted a multi-stage consultation to develop a framework for
      the study of a paediatric telepsychiatry programme. Emphasis was placed on
      ensuring the participation of stakeholders in the design and response stage of
      the evaluation. A three-part approach was taken that comprised an opinion scan,
      focus groups and individual interviews. This resulted in the identification of
      specific areas of enquiry for the evaluation. One of the key points to emerge was
      that attending to context is vital. In the case of telepsychiatry, it is critical
      to understand the nuances of the local community for whom consultations are being
      provided. This involves considering the 'social ecology' of each evaluation site.
      The evaluation should take the form of a dialogue between the evaluators and
      those being evaluated, in order to maximize the uptake and integration of its
      findings. The framework we have developed should be viewed as a guide that is
      general enough to be used in the design of many different types of telepsychiatry
      programme.

PMID- 15165444
TI  - An assessment of the readiness of hospice organizations to accept technological
      innovation.
AB  - We surveyed seven of the 62 certified hospice programmes in the state of
      Missouri. The survey consisted of 19 questions that covered demographic
      information, how employees received new information, the current use of various
      forms of technology, employees' comfort with technology and their perceptions of
      the use of video-phones. A total of 124 surveys were returned. Respondents were
      categorized within the following disciplines: nurses (48%), administrators and
      nurse supervisors (6%), social workers (9%), physicians (3%), home health aids
      (18%), chaplains (5%) and other staff (e.g. clerical and bereavement staff)
      (12%). Staff reported using several types of technological device at work but not
      a video-phone or a Web camera. There were significant differences between
      hospices in the degree of use of computers at work, the number of devices used at
      work and the perceived benefits of video-phone technology. There were significant
      differences between disciplines in the degree of use of computers at work and at
      home, the number of devices used at work, and their comfort both with the use of
      new technology and with the idea of introducing new technology to patients and
      their families. Because there were variations in the perceived usefulness of
      video-phones for hospice care, the introduction of such equipment would require
      substantial involvement of the users.

PMID- 15165445
TI  - Performance of a web-based, realtime, tele-ultrasound consultation system over
      high-speed commercial telecommunication lines.
AB  - A Web-based, realtime, tele-ultrasound consultation system was designed. The
      system employed ActiveX control, MPEG-4 coding of full-resolution ultrasound
      video (640 x 480 pixels at 30 frames/s) and H.320 videoconferencing. It could be
      used via a Web browser. The system was evaluated over three types of commercial
      line: a cable connection, ADSL and VDSL. Three radiologists assessed the quality
      of compressed and uncompressed ultrasound video-sequences from 16 cases (10
      abnormal livers, four abnormal kidneys and two abnormal gallbladders). The
      radiologists' scores showed that, at a given frame rate, increasing the bit rate
      was associated with increasing quality; however, at a certain threshold bit rate
      the quality did not increase significantly. The peak signal to noise ratio (PSNR)
      was also measured between the compressed and uncompressed images. In most cases,
      the PSNR increased as the bit rate increased, and increased as the number of
      dropped frames increased. There was a threshold bit rate, at a given frame rate,
      at which the PSNR did not improve significantly. Taking into account both sets of
      threshold values, a bit rate of more than 0.6 Mbit/s, at 30 frames/s, is
      suggested as the threshold for the maintenance of diagnostic image quality.

PMID- 15165446
TI  - The feasibility of telemedicine for the training and supervision of general
      practitioners performing ultrasound examinations of patients with urinary tract
      symptoms.
AB  - Ultrasound examinations were carried out by a general practitioner on patients
      who presented with lower urinary tract symptoms. To assist in the interpretation
      of ultrasound anatomy, still images were captured during the ultrasound
      examination and transmitted to a university expert. In total 15 telemedicine
      sessions were conducted, using PC-based videoconferencing equipment connected by
      ISDN at 128 kbit/s. Fifteen patients were randomly selected and both the
      transmitted and hard-copy images (printed on thermal paper) were graded for
      technical quality. Data were missing for 13 of the possible 105 paired
      comparisons, as some images could not be evaluated. Overall agreement between the
      technical quality scores for the transmitted and hard-copy images was poor
      (weighted kappa=0.04). The 105 transmitted images were also rated for their
      diagnostic quality: 90% were classified as diagnostic and 10% were judged to be
      non-diagnostic. The results show the feasibility of tele-ultrasound in primary
      care. The general practitioner concerned benefited from regular ultrasound
      training and supervision, and achieved a satisfactory level of clinical
      competency in scanning the prostate, bladder and kidneys.

PMID- 15165447
TI  - Tele-education in dermatopathology of pigmented lesions: is dermoscopy a valuable
      tool?

PMID- 15165449
TI  - Tissue engineering of cartilage using a hybrid scaffold of synthetic polymer and
      collagen.
AB  - A biodegradable hybrid scaffold of synthetic polymer, poly (DL-lactic-co-glycolic
      acid) (PLGA), and naturally derived polymer, collagen, was prepared by forming
      collagen microsponges in the pores of PLGA sponge. This was then used as the
      three-dimensional scaffold for tissue engineering of bovine articular cartilage,
      both in vitro and in vivo. In vitro studies show that hybridization with collagen
      facilitated cell seeding in the sponge and raised seeding efficiency.
      Chondrocytes adhered to the collagen microsponges, where they proliferated and
      secreted extracellular matrices with time, filling the space within the sponge.
      Hematoxylin and eosin staining revealed that most of the chondrocytes after 4
      weeks of culture, and almost all cell types after 6 weeks of culture, maintained
      their phenotypically rounded morphology. While new tissue formed, the scaffold
      degraded and lost almost 36.9% of its original weight after 10 weeks.
      Subcutaneous implantation studies in nude mice demonstrated more homogeneous
      tissue formation in hybrid sponge than in PLGA sponge. The new tissue formed
      maintained the original shape of the hybrid sponge. The synthetic PLGA sponge,
      serving as a skeleton, facilitated easy formation into desired shapes and
      provided appropriate mechanical strength to define the ultimate shape of
      engineered tissue. Incorporation of collagen microsponges facilitated cell
      seeding and homogeneous cell distribution and created a favorable environment for
      cellular differentiation. The hybrid sponge could therefore represent a promising
      candidate as a three-dimensional scaffold for articular cartilage tissue
      engineering.

PMID- 15165450
TI  - Role of the periosteal flap in chondrocyte transplantation: an experimental study
      in rabbits.
AB  - To determine the role of the periosteal flap in chondrocyte transplantation for
      the treatment of articular cartilage defects, a cartilage defect was created on
      the patellar groove of the rabbit knee. The defect was filled with chondrocytes
      cultured in collagen gel, and was covered with a periosteal flap the cambial
      layer of which was facing the patella (P group), or facing down against the bone
      marrow (M group). The same defect was covered with a periosteal flap that was
      frozen and thawed three times (F group), and an artificial collagen film (C
      group). At 3 and 6 months, the defects were filled with reparative tissues that
      showed a smooth surface and resembled hyaline cartilage in the P, M, and F
      groups. There were no significant differences between the reparative tissues in
      the three groups histologically, immunohistochemically, biochemically, and
      biomechanically, although the collagen film fell down into the defect and the
      reparative tissue had a fibrous tissue-like appearance. These results showed that
      the periosteal flap does not have a beneficial humoral or cellular effect on the
      formation of reparative tissue, suggesting that the periosteal flap might act as
      a mechanical barrier to prevent leakage of grafted chondrocytes.

PMID- 15165451
TI  - Application of physical force is essential to enrich for epidermal stem cells in
      primary human keratinocyte isolation.
AB  - We present an improved method to isolate epidermal cells and to enrich stem cell
      populations. The new method utilizes magnetic stirring during digestion of skin
      with trypsin-EDTA (magnetic stirring method). The magnetic stirring method
      significantly improves both cell yield and colony-forming efficiency (CFE)
      relative to conventional epidermal cell isolation methods, such as those
      involving trypsin-EDTA only, thermolysin, or dispase. The cell yield and the
      total number of colony-forming cells per square centimeter of adult foreskin were
      7,064,000 +/- 95,000 cells and 96,030 +/- 31,990 cells by the magnetic stirring
      method, 1,128,000 +/- 111,000 cells and 10,192 +/- 2941 cells by trypsin-EDTA
      only, 3,279,000 +/- 842,000 cells and 5851 +/- 2989 cells by thermolysin, and
      1,443,000 +/- 507,000 cells and 8843 +/- 3388 cells by dispase, respectively. The
      CFE was 1.15 +/- 0.32% by magnetic stirring, 0.95 +/- 0.35% by trypsin-EDTA only,
      0.28 +/- 0.12% by thermolysin, and 0.83 +/- 0.30% by dispase. The levels of
      surface beta(1)-integrin expression skewed to the right with the magnetic
      stirring method, implying increased proportion of beta(1)-integrin-bright cells
      (putative stem cells). Isolated keratinocytes developed fully differentiated
      epidermis when they were grafted onto nude mice. In conclusion, cell isolation by
      the magnetic stirring method is advantageous over conventional epidermal cell
      isolation methods, by which full range of basal epidermal cells including stem
      cells, transiently amplifying cells, and differentiating cells can be isolated
      and allow shorter expansion time for maximal coverage of wound sites after
      biopsies are taken from patients.

PMID- 15165452
TI  - Expression of fibrinolytic and coagulation factors in cocultured human
      endothelial and smooth muscle cells.
AB  - Interactions between endothelial cells and smooth muscle cells are interesting
      from a tissue-engineering point of view. We have developed a coculture system
      that allows direct contact between these two cell types. The fibrinolytic factors
      PAI-1, tPA, and uPA and the coagulation factor TF, were studied at the gene level
      by RT-PCR and at the protein level by ELISA. Significant changes of all studied
      factors were seen at the gene level in cocultured endothelial cells. tPA and TF
      were upregulated 4- and 7-fold, respectively, and PAI-1 and uPA were
      downregulated 4- and 1.5-fold, respectively, compared with single-cultured
      controls. In cocultured smooth muscle cells alterations of PAI-1 and TF were
      significant, with a 1.5-fold upregulation of PAI-1 and a 2.5-fold downregulation
      of TF. Results at the protein level mirrored the gene expression results. These
      findings indicate that cocultured endothelial cells are rendered both
      hypercoagulative and hyperfibrinolytic.

PMID- 15165453
TI  - Characterization of the response of bone marrow-derived progenitor cells to
      cyclic strain: implications for vascular tissue-engineering applications.
AB  - One of the major failings in vascular tissue engineering is the limited capacity
      of autologous differentiated cells to reconstitute tissues. A logical solution is
      to use multipotent progenitor cells, which in vascular treatments have been
      underutilized. Although biochemical stimulation has been explored to
      differentiate bone marrow-derived progenitor cells (BMPCs) to smooth muscle cells
      (SMCs), the use of biomechanical forces in differentiation remains unexplored.
      The purpose of this work was to explore the effects of cyclic strain alone on
      BMPC morphology, proliferation, and differentiation. BMPCs were isolated from rat
      bone marrow and, after 7 days in culture, the cells grew in distinct multilayered
      colonies. BMPCs were stimulated with 10% strain at 1 Hz for 7 days. Observations
      showed that cyclic strain inhibited proliferation (p < 0.05) and caused alignment
      of the cells (p < 0.05) and of the F-actin cytoskeleton perpendicular to the
      direction of strain. In addition, cyclic strain resulted in expression by the
      cells of vascular smooth muscle alpha-actin and h1-calponin. This work
      demonstrates the potential of physiologic biomechanical stimulation in the
      differentiation of BMPCs to SMCs, and this could have important implications for
      vascular tissue engineering and other therapies in which cell sourcing is a major
      concern.

PMID- 15165454
TI  - Human adipose-derived adult stem cells produce osteoid in vivo.
AB  - Adult subcutaneous fat tissue is an abundant source of multipotent cells.
      Previous studies from our laboratory have shown that, in vitro, adipose-derived
      adult stem (ADAS) cells express bone marker proteins including alkaline
      phosphatase, type I collagen, osteopontin, and osteocalcin and produce a
      mineralized matrix as shown by alizarin red staining. In the current study, the
      ADAS cell ability to form osteoid in vivo was determined. ADAS cells were
      isolated from liposuction waste of three individual donors and expanded in vitro
      before implantation. Equal numbers of cells (3 x 10(6)) were loaded onto either
      hydroxyapatite/tricalcium phosphate (HA-TCP) cubes or the collagen/HA-TCP
      composite matrix, Collagraft, and then implanted subcutaneously into SCID mice.
      After 6 weeks, implants were removed, fixed, and demineralized and sectioned for
      hematoxylin and eosin staining. Osteoid formation was observed in 80% of HA-TCP
      implants loaded with ADAS cells. Only 20% of Collagraft implants were positive
      for the presence of osteoid matrix. Whereas 100% of HA-TCP implants loaded with
      hFOB 1.19 cells formed osteoid, Collagraft loaded with hFOB 1.19 cells displayed
      a high degree of adipose tissue within the matrix. Immunostaining of serial
      sections for human nuclear antigen demonstrated that the osteoid contained human
      cells. Osteoid formation was not observed in control HA-TCP or Collagraft
      matrices implanted without cells. In summary, the data demonstrate the ability of
      ADAS cells to form osteoid matrix in vivo. Because of their abundance and
      accessibility, ADAS cells may prove to be a novel cell therapeutic for bone
      repair and regeneration.

PMID- 15165455
TI  - Subcutaneous adipocytes can differentiate into bone-forming cells in vitro and in
      vivo.
AB  - Interconversion of bone marrow osteoblasts and adipocytes has been reported
      previously. However, the osteogenic potential of extramedullary adipocytes is not
      known. Thus, we incubated a pure culture of human subcutaneous adipocytes in
      control medium for 1-2 weeks. Afterward, the cells were incubated in either
      osteoblast medium (OB medium) containing various combinations of calcitriol,
      dexamethasone, ascorbic acid, and beta-glycerophosphate or in adipocyte medium
      (AD medium) containing HEPES, biotin, pantothenate, insulin, triiodothyronine,
      dexamethasone, and isobutylmethylxanthine for 4 weeks. Expression of osteoblastic
      and adipocytic phenotypes was examined by determination of lineage-specific mRNA
      markers and in vitro adipocyte and osteoblast formation. Cells were also
      implanted, mixed with hydroxyapatite-tricalcium phosphate powder, in the
      subcutaneous tissue of immunodeficient mice in order to assess in vivo bone
      formation potential. One week after incubation in control medium, cells formed
      fusiform elongated fibroblast-like cells. In OB medium, cells stained positive
      for alkaline phosphatase (AP) and expressed mRNAs encoding Cbfa1/Runx2, AP, and
      osteocalcin. In AD medium cells reacquired adipocyte morphology with multilocular
      lipid-filled cells. Also, the cells expressed adipocyte-specific mRNA markers:
      lipoprotein lipase and peroxisome proliferator-activated receptor gamma2. Bone
      was formed only in the in vivo implants of cells incubated in OB medium. In
      conclusion, extramedullary adipocytes can transdifferentiate to bone-forming
      cells. Because of their ease of isolation, adipocytes may be good candidates for
      tissue-engineering protocols aimed at creating bone tissue for the repair of
      nonunion fractures and large bone defects.

PMID- 15165456
TI  - Effects of Wnt signaling on proliferation and differentiation of human
      mesenchymal stem cells.
AB  - Mesenchymal stem cells are pluripotent cells from bone marrow, which can be
      differentiated into the osteogenic, chondrogenic, and adipogenic lineages in
      vitro and are a source of cells in bone and cartilage tissue engineering. An
      improvement in current tissue-engineering protocols requires more detailed
      insight into the molecular cues that regulate the distinct steps of osteochondral
      differentiation. Because Wnt signaling has been widely implicated in mesenchymal
      differentiation, we analyzed the role of Wnt signaling in human mesenchymal stem
      cell (hMSC) biology by stimulation of the pathway with lithium chloride and Wnt3A
      conditioned medium. We demonstrate a role for low levels of Wnt signaling in
      proliferation of uncommitted hMSCs and confirm that Wnt signaling controls
      osteoprogenitor proliferation. On the other hand, at high Wnt levels we observed
      a block in adipogenic differentiation and an increase in the expression of
      alkaline phosphatase, suggesting a role in the initiation of osteogenesis. The
      results of this study suggest that bone tissue engineering could benefit from the
      activation of critical levels of Wnt signaling at defined stages of
      differentiation. Moreover, our data suggest that hMSCs provide a valid in vitro
      model to study the role of Wnt signaling in mesenchymal biology.

PMID- 15165457
TI  - Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac
      function after myocardial infarction.
AB  - Current efforts in cardiac tissue engineering center around the use of scaffolds
      that deliver cells to the epicardial surface. In this study, we examined the
      effects of fibrin glue as an injectable scaffold and wall support in ischemic
      myocardium. The left coronary artery of rats was occluded for 17 min, followed by
      reperfusion. Echocardiography was performed 8 days after infarction. One to 2
      days later, either 0.5% bovine serum albumin (BSA) in phosphate-buffered saline,
      fibrin glue alone, skeletal myoblasts alone, or skeletal myoblasts in fibrin glue
      were injected into the ischemic left ventricle. Echocardiography was again
      performed 5 weeks after injection. The animals were then sacrificed and the
      hearts were fresh frozen and sectioned for histology and immunohistochemistry.
      Both the fractional shortening (FS) and infarct wall thickness of the BSA group
      decreased significantly after 5 weeks (p = 0.0005 and 0.02, respectively). In
      contrast, both measurements for the fibrin glue group, cells group, and cells in
      fibrin glue group did not change significantly (FS: p = 0.18, 0.89, and 0.19,
      respectively; wall thickness: p = 0.40, 0.44, 0.43, respectively). Fibrin glue is
      capable of preserving infarct wall thickness and cardiac function after a
      myocardial infarction in rats and may be useful as a biomaterial scaffold for
      myocardial cell transplantation.

PMID- 15165458
TI  - Noninvasive in situ evaluation of osteogenic differentiation by time-resolved
      laser-induced fluorescence spectroscopy.
AB  - The clinical implantation of bioengineered tissues requires an in situ
      nondestructive evaluation of the quality of tissue constructs developed in vitro
      before transplantation. Time-resolved laser-induced fluorescence spectroscopy (TR
      LIFS) is demonstrated here to noninvasively monitor the formation of osteogenic
      extracellular matrix (ECM) produced by putative stem cells (PLA cells) derived
      from human adipose tissue. We show that this optical spectroscopy technique can
      assess the relative expression of collagens (types I, III, IV, and V) within
      newly forming osteogenic ECM. The results are consistent with those obtained by
      conventional histochemical techniques (immunofluorescence and Western blot) and
      demonstrate that TR-LIFS is a potential tool for monitoring the expression of
      distinct collagen types and the formation of collagen cross-links in intact
      tissue constructs.

PMID- 15165459
TI  - Short collagen fibers provide control of contraction and permeability in
      fibroblast-seeded collagen gels.
AB  - Tissue engineering may allow for the reconstruction of breast, facial, skin, and
      other soft tissue defects in the human body. Cell-seeded collagen gels are a
      logical choice for creating soft tissues because they are biodegradable, mimic
      the natural tissue, and provide a three-dimensional environment for the cells.
      The main drawback associated with this approach, however, is the subsequent
      contraction of the gel by the constituent cells, which severely reduces
      permeability, initiates apoptosis, and precludes control of the resulting shape
      and size of the construct. In this study, type I collagen gels were seeded with
      fibroblasts and cast either with or without the addition of short collagen
      fibers. Gel contraction was monitored and permeability was assessed after 7 and
      14 days in culture. The addition of short collagen fibers both significantly
      limited contraction and increased permeability of fibroblast-seeded collagen
      gels. The addition of short collagen fibers had no detrimental effect on cell
      proliferation, and there were a high number of viable fibroblasts in gels with
      fibers and gels without fibers. Gels containing short collagen fibers
      demonstrated permeabilities that were 100 to 1000 times greater than controls and
      also closely maintained their casting dimensions (never less than 96% of
      original). By limiting contraction and maintaining permeability, the
      incorporation of short collagen fibers should enable the creation of larger
      constructs by allowing for greater nutrient diffusion, and permit the creation of
      more complicated shapes during gel casting.

PMID- 15165460
TI  - PEGylation does not impair insulin efficacy in three-dimensional cartilage
      culture: an investigation toward biomimetic polymers.
AB  - A major goal in tissue engineering is the controlled application of growth
      factors. As a novel application system, we are currently developing biomimetic
      polymers that are processed into three-dimensional scaffolds. Bioactive proteins
      will be covalently bound to the polymers via a poly(ethylene glycol) (PEG)
      linker. Of paramount importance is the maintenance of the biological activity of
      the protein after PEGylation and covalent binding to the polymer. Therefore,
      within this study, insulin used as a model protein was PEGylated with an active
      succinimidyl ester of poly(ethylene glycol) (SS-NH-PEG) (MW ~2000) and biological
      effects of the protein-PEG conjugate were monitored in comparison with unmodified
      insulin. No significant differences in chondrocyte proliferation were observed in
      a conventional proliferation assay after treatment with insulin or PEGylated
      insulin. In a complex three-dimensional cartilage-engineering model the effects
      of insulin and PEGylated insulin were investigated over a wide concentration
      range (0.025-25 microg/mL). Insulin and PEGylated insulin at equivalent
      concentrations resulted in cartilaginous tissue constructs exhibiting identical
      wet weight, cell number, biochemical composition of the extracellular matrix, and
      histological appearance, both compounds significantly improving tissue quality as
      compared with control constructs. In conclusion, the presented study demonstrates
      that PEGylation of insulin using SS-NH-PEG did not change the activity of the
      protein in a complex biological environment and is regarded as a step toward the
      development of biomimetic polymers.

PMID- 15165461
TI  - Toward the development of biomimetic polymers by protein immobilization:
      PEGylation of insulin as a model reaction.
AB  - Many current tissue-engineering investigations aim at the rational control of
      cell adhesion and tailored composition of biomaterial surfaces by immobilizing
      various protein and peptide components, such as growth factors. As a step on the
      way to develop polymers that allow for such surface modifications, water-soluble
      polymers were used as model substances to examine reactions with proteins
      containing amine groups. Consequently, the uncommon PEGylation of insulin in
      aqueous buffers was used to characterize reaction products and simulate the
      intended immobilization step for surface modification. Amine reactive
      poly(ethylene glycol)s were synthesized and characterized by (1)H nuclear
      magnetic resonance and gel-permeation chromatography. Furthermore, the model
      protein insulin was characterized concerning its accessible amino groups, using a
      fluorescent dye (TAMRA-SE). The resulting reaction products were identified by
      reversed-phase high-performance liquid chromatography and electrospray mass
      spectrometry. After PEGylation with hydrolytically stable poly(ethylene glycol)
      succinimidyl ester, the obtained PEGylated insulin was investigated by gel
      filtration chromatography, indicating successful attachment of the hydrophilic
      polymer chains. Application of an aqueous PEGylation scheme opens the door to the
      immediate investigation of various growth factors in cell culture, allowing for
      direct assessment of biological activity after forming the polymer-protein
      constructs with regard to later immobilization on surfaces.

PMID- 15165462
TI  - Local effects on triiodothyronine-treated polyglactin sutures on regeneration
      across peripheral nerve defects.
AB  - We have previously described a new and simple method for nerve repair in which
      continuous longitudinal polyglactin sutures alone are used to bridge limited
      nerve defects in rats. Here we examined whether such sutures could be used to
      deliver a growth-promoting substance, triiodothyronine (T(3)), and enhance
      regeneration of the rat sciatic nerve. Sutures were pretreated in highly
      concentrated solutions of T(3) for 24 h. In vitro measurements showed that such
      sutures released T(3) with an initial rapid phase followed by a slow-release
      phase lasting at least 3 weeks. Bilateral sciatic nerve defects (7 mm) in rats
      were bridged by either T(3)- or saline-incubated sutures. Immunocytochemistry for
      Schwann cells and axons at 2 weeks showed no differences in Schwann cell
      distribution or axonal outgrowth length. Morphometric analysis 4 and 12 weeks
      after the repair revealed a slight but significant (p < 0.05) increase in the
      mean myelin area in T(3)-treated nerves. No differences were seen in the number
      of axons or return of force in the gastrocnemius muscle at 12 weeks. The results
      show that sutures can be used both for the bridging of defects in peripheral
      nerves and for the delivery of a growth-promoting substance to regenerating nerve
      structures.

PMID- 15165463
TI  - Novel starch-based scaffolds for bone tissue engineering: cytotoxicity, cell
      culture, and protein expression.
AB  - Starch-based biomaterials and scaffolds have been proposed for several biomedical
      applications. In the present work new scaffolds based on a 50/50 (wt%) blend of
      corn starch/ethylene-vinyl alcohol (SEVA-C) were studied. These scaffolds were
      processed by a melt-based technology, which has been used before with other
      starch-based materials but never with SEVA-C. Scanning electron microscopy (SEM)
      observation showed that the developed porous structures were 60% porous with pore
      size between 200 and 900 microm and a reasonable degree of interconnectivity.
      Moreover, scaffolds presented a compressive modulus of 117.50 +/- 3.7 MPa and a
      compressive strength of 20.8 +/- 2.4 MPa. Cytotoxicity evaluation was performed
      according to ISO/EN 10993 part 5 guidelines, and revealed that the developed
      scaffolds were nontoxic and did not inhibit cell growth. Direct contact assays
      were also carried out by use of a cell line of human osteoblast-like cells (SaOS
      2). Cells were seeded (3 x 10(5) per scaffold) and allowed to grow for 4 weeks at
      37 degrees C, in a humidified atmosphere containing 5% CO(2). Total protein assay
      showed that the cells were able to grow for the 4 weeks of the experiment. These
      data were further confirmed by SEM. Moreover, a cell viability assay (MTS test)
      demonstrated that cells were perfectly viable after the 4 weeks of culture,
      showing the adequacy of the developed structure in supporting them. Finally,
      Western blot analysis revealed that osteopontin was being actively expressed by
      the cells, which, in association with collagen deposition observed by SEM, seems
      to indicate that bone extracellular matrix was being deposited. Consequently it
      is believed that starch-based scaffolds should be considered as an alternative
      for bone tissue-engineering applications in the near future.

PMID- 15165464
TI  - Traveling wave model to interpret a wound-healing cell migration assay for human
      peritoneal mesothelial cells.
AB  - The critical determinants of the speed of an invading cell front are not well
      known. We performed a "wound-healing" experiment that quantifies the migration of
      human peritoneal mesothelial cells over components of the extracellular matrix.
      Results were interpreted in terms of Fisher's equation, which includes terms for
      the modeling of random cell motility (diffusion) and proliferation. The model
      predicts that, after a short transient, the invading cell front will move as a
      traveling wave at constant speed. This is consistent with the experimental
      findings. Using the model, a relationship between the rate of cell proliferation
      and the diffusion coefficient was obtained. We used the model to deduce the cell
      diffusion coefficients under control conditions and in the presence of collagen
      IV and compared these with other published data. The model may be useful in
      analyzing the invasive capacity of cancer cells as well in predicting the
      efficacy of growth factors in tissue reconstruction, including the development of
      monolayer sheets of cells in skin engineering or the repair of injured corneas
      using grafts of cultured cells.

PMID- 15165466
TI  - Alginate enhances elongation of early regenerating axons in spinal cord of young
      rats.
AB  - Freeze-dried alginate sponge cross-linked with covalent bonds has been
      demonstrated to enhance nerve regeneration in peripheral nerves and spinal cords.
      The present study examined, at early stages after surgery, the outgrowth of
      regenerating axons and reactions of astrocytes at the stump of transected spinal
      cord in young rats. Two segments (Th7-8) were resected, and alginate was
      implanted in the lesion. As controls, collagen gel was implanted in place of
      alginate or the lesion was left without implantation. Two and 4 weeks after
      surgery, nerve outgrowth and astrocyte reactions were examined. Many regenerating
      axons, some of which were accompanied by astrocytic processes, were found to
      extend from the stump into the alginate-implanted lesion. In the all nonimplanted
      animals, large cystic cavities were formed at both interfaces with no definite
      axonal outgrowth into the lesion. In collagen-implanted animals, cavity formation
      was found in some rats, and regenerating axons once formed at the stumps did not
      extend further into the lesion. Astrocytic processes extending into alginate
      implanted lesion had no basal laminae, whereas those found in control experiments
      were covered by basal laminae. These findings suggest that alginate contributed
      to reducing the barrier composed of connective tissues and reactive astrocytic
      processes, and served as a scaffold for the outgrowth of regenerating axons and
      elongation of astrocytic processes.

PMID- 15165467
TI  - Evaluation of smooth muscle cell response using two types of porous polylactide
      scaffolds with differing pore topography.
AB  - The goal of tissue engineering is to create bioartificial tissues for the
      replacement of failed or nonfunctional tissue. Porous tissue-engineered scaffolds
      may be created through a solvent-casting/porogen-leaching technique. Almost
      exclusively, sodium chloride (NaCl) is the porogen of choice. Previous studies
      have demonstrated the importance of porosity and pore size in cell adhesion and
      tissue development, yet the impact of porogen morphology and the chemical effect
      of porogen residual has not been fully explored. Poly-L-lactide (PLLA) scaffolds
      were manufactured by a solvent-casting, particulate-leaching method with either
      glucose or NaCl porogen in an effort to vary pore characteristics and,
      subsequently, cell adhesion and tissue development. Porogen influence on scaffold
      morphology and topography was compared via histological techniques and
      qualitative surface characteristics. Using an in vitro model, scaffolds were
      seeded with rat aortic smooth muscle cells (SMCs) and evaluated over a 28-day
      period. Cell attachment and proliferation were subsequently evaluated. Results
      indicate that initial SMC attachment is higher for scaffolds manufactured with
      NaCl rather than glucose. The proliferation of SMCs was higher for scaffolds
      manufactured with glucose and, by day 28, scaffolds manufactured with glucose
      supported a higher cell population than those processed using NaCl porogen.

PMID- 15165465
TI  - Laser printing of pluripotent embryonal carcinoma cells.
AB  - A technique by which to print patterns and multilayers of scaffolding and living
      cells could be used in tissue engineering to fabricate tissue constructs with
      cells, materials, and chemical diversity at the micron scale. We describe here
      studies using a laser forward transfer technology to print single-layer patterns
      of pluripotent murine embryonal carcinoma cells. This report focuses on verifying
      cell viability and functionality as well as the ability to differentiate cells
      after laser transfer. We find that when cells are printed onto model tissue
      scaffolding such as a layer of hydrogel, greater than 95% of the cells survive
      the transfer process and remain viable. In addition, alkaline comet assays were
      performed on transferred cells, showing minimal single-strand DNA damage from
      potential ultraviolet-cell interaction. We also find that laser-transferred cells
      express microtubular associated protein 2 after retinoic acid stimulus and myosin
      heavy chain protein after dimethyl sulfoxide stimulus, indicating successful
      neural and muscular pathway differentiation. These studies provide a foundation
      so that laser printing may next be used to build heterogeneous multilayer
      cellular structures, enabling cell growth and differentiation in heterogeneous
      three-dimensional environments to be uniquely studied.

PMID- 15165468
TI  - Bovine primary chondrocyte culture in synthetic matrix metalloproteinase
      sensitive poly(ethylene glycol)-based hydrogels as a scaffold for cartilage
      repair.
AB  - A poly(ethylene glycol) (PEG)-based hydrogel was used as a scaffold for
      chondrocyte culture. Branched PEG-vinylsulfone macromers were end-linked with
      thiol-bearing matrix metalloproteinase (MMP)-sensitive peptides
      (GCRDGPQGIWGQDRCG) to form a three-dimensional network in situ under physiologic
      conditions. Both four- and eight-armed PEG macromer building blocks were
      examined. Increasing the number of PEG arms increased the elastic modulus of the
      hydrogels from 4.5 to 13.5 kPa. PEG-dithiol was used to prepare hydrogels that
      were not sensitive to degradation by cell-derived MMPs. Primary bovine calf
      chondrocytes were cultured in both MMP-sensitive and MMP-insensitive hydrogels,
      formed from either four- or eight-armed PEG. Most (>90%) of the cells inside the
      gels were viable after 1 month of culture and formed cell clusters. Gel matrices
      with lower elastic modulus and sensitivity to MMP-based matrix remodeling
      demonstrated larger clusters and more diffuse, less cell surface-constrained cell
      derived matrix in the chondron, as determined by light and electron microscopy.
      Gene expression experiments by real-time RT-PCR showed that the expression of
      type II collagen and aggrecan was increased in the MMP-sensitive hydrogels,
      whereas the expression level of MMP-13 was increased in the MMP-insensitive
      hydrogels. These results indicate that cellular activity can be modulated by the
      composition of the hydrogel. This study represents one of the first examples of
      chondrocyte culture in a bioactive synthetic material that can be remodeled by
      cellular protease activity.

PMID- 15165469
TI  - Photocured, styrenated gelatin-based microspheres for de novo adipogenesis
      through corelease of basic fibroblast growth factor, insulin, and insulin-like
      growth factor I.
AB  - De novo adipose tissue formation appears to proceed via two different biological
      events: neovascularization and spontaneous accumulation of preadipocytes and
      subsequent differentiation to mature adipocytes. In this article, we perform
      accelerated de novo adipose tissue engineering using photocured, styrenated,
      gelatin-based microspheres (SGMs) with different drug release rates of
      immobilized angiogenic and adipogenic factors. The concept of this system is to
      induce neovascularization and migration of endogenous preadipocytes by the rapid
      delivery of the angiogenic factor basic fibroblast growth factor (bFGF), followed
      by the proliferation and differentiation of preadipocytes into adipocytes by the
      prolonged delivery of the adipogenic factors, insulin and insulin-like growth
      factor I (IGF-I). Bioactive substance-immobilized SGMs with different drug
      release rates were prepared with different gelatin concentrations. An in vitro
      study showed the prolonged release of an immobilized model protein and the
      dependence of drug release rate on gelatin concentration. After the subcutaneous
      injections of SGMs immobilized with these bioactive substances in different
      combinations, the formation of masses or clusters of adipocytes was observed in
      rats. Triglyceride content in the injection site for the group that received bFGF
      , insulin-, and IGF-I-immobilized SGMs was significantly higher than that for the
      group that received insulin- and IGF-I-immobilized SGMs 4 weeks after the
      injection of microspheres. These results suggest that the system developed here
      is effective for the de novo formation of adipose tissue as it enables the
      induction of the two-step biological reaction by single injection.

PMID- 15165470
TI  - In situ tissue engineering of periodontal tissues by seeding with periodontal
      ligament-derived cells.
AB  - The feasibility of an in situ tissue-engineering method employing cell-based
      therapy with autologous periodontal ligament-derived cells was investigated.
      Periodontal ligament cells were obtained from six beagle dogs. Periodontal
      fenestration defects (6 x 4 mm) were created bilaterally at a location 6 mm
      apical to the marginal alveolar crest in the maxillary canines. Alkaline
      phosphatase-positive periodontal ligament cells (3 x 10(5) cells) were seeded
      onto a collagen sponge scaffold just before implantation. One defect was filled
      with the cell-scaffold construct, and another was left empty as the control. All
      animals were killed 4 weeks after surgery, and specimens were evaluated
      histomorphometrically. All the histomorphometrical data were analyzed by three
      way analysis of variance with the Bonferroni multiple comparisons test.
      Regeneration of apical tissue was faster than that of coronal and isolated
      tissues on the control side (apical > coronal > isolated; p < 0.0001). On the
      other hand, on the cell-seeded side, regeneration of the cementum was observed
      uniformly on the root surface. Our data suggest that the seeded cells induced
      cementum regeneration on the root surface, indicating the potential of in situ
      tissue engineering using autologous cells for the regeneration of periodontal
      tissues.

PMID- 15165471
TI  - Maintenance of morphology and growth of ovarian follicles in suspension culture.

PMID- 15165472
TI  - Engineering the hepatocyte differentiation-proliferation balance by acellular
      cadherin micropresentation.
AB  - The successful development of bioartificial and cell-based liver support systems
      relies on the identification of molecular mechanisms controlling the balance
      between hepatocellular proliferation and differentiation. Although a definitive
      function-inductive role for the cell-cell adhesion molecule, E-cadherin, was
      established through lateral cadherin-cadherin engagement in hepatocyte cocultures
      (Brevia, T.A., and Moghe, P.V. Biotechnol. Bioeng. 76, 295, 2001), the roles of
      other modes of cadherin presentation are not well understood. Further,
      alternative cadherin display configurations promoting cell growth/proliferative
      pathways, a major requisite for sustainable engineered tissues, remain to be
      identified. In this report, we employed protein A-functionalized polymeric
      microsphere substrates that specifically bound self-dimerizing cadherin-IgG/Fc
      fusion chimeras via their Fc regions, thereby orienting them outward for active
      adhesion, and presented the E-cadherin chimeras basally to cultured rat
      hepatocytes to study the effects of cadherin display on cell proliferative
      potential and differentiated function. In contrast to the previously documented
      function-inductive roles of laterally expressed cadherin, basal acellular
      cadherin presentation resulted in an increase in hepatocyte DNA synthesis and
      cell divisions, accompanied by a decrease in the expression of a key marker of
      liver-specific function, albumin message levels. Next, we probed the relative
      effect of basal exogenous display of acellular cadherins on the inductive phase
      of differentiation within hepatocyte cocultures with cadherin-expressing L929
      cells. When acellular cadherins were applied to hepatocyte cocultures involving
      chaperone cell-mediated cadherin presentation, the previously reported function
      inductive effects of cadherins on hepatocyte function were reversed, resulting in
      lower levels of albumin and urea secretion indicating a dominance of acellular
      cadherin effects. Our results demonstrate that cadherins are important regulators
      of the balance between hepatocyte differentiation and proliferation, and
      furthermore that the direction of balance shift may be dependent on the method of
      cadherin presentation. Thus, the geometric display of cadherin could be a
      potential parameter to switch hepatocyte functional-proliferative balance and may
      aid in customizing scaffolds for regulating hepatic tissue dynamics.

PMID- 15165473
TI  - New multi-cue bioreactor for tissue engineering of tubular cardiovascular samples
      under physiological conditions.
AB  - In the present study we have developed a multi-cue bioreactor (MCB) that is
      capable of delivering a range of stimuli to assist the development of a tissue
      engineered construct. The MCB provides an accurate and utilizable computer
      controlled pulsatile pump and strain induction mechanism and it has the
      capability of applying physiological conditions to samples. The device described
      here emulates the pressure and straining environment found at the aortic root.
      This function, along with an integral perfusion and sterile containment system,
      allows for long-term culture and whole-tissue testing capability. Aortic and
      pulmonary arteries were obtained from freshly isolated porcine hearts and
      subjected to various loading regimens (Deltapressure/flow/force). Through
      analyzing data acquired by the MCB transducer array it was possible to
      differentiate the dynamic mechanical properties of the tissue types tested. In
      addition, the MCB illustrates a novel concept in cardiovascular tissue
      engineering: being able to support long-term tissue culture of cell-seeded
      substrates while they are under the influence of mechanical cues. After 7 days of
      pulsation in the MCB cell alignment was observed. The MCB represents a versatile
      model that will enable the development of tissue engineering not only for
      cardiovascular tissue, but for all tubular tissues such as esophageal, tracheal,
      and bronchial systems.

PMID- 15165474
TI  - Transduction of passaged human articular chondrocytes with adenoviral,
      retroviral, and lentiviral vectors and the effects of enhanced expression of
      SOX9.
AB  - Chondrocytes form and maintain the extracellular matrix of cartilage. The cells
      can be isolated from cartilage for applications such as tissue engineering, but
      their expansion in monolayer culture causes a progressive loss of chondrogenic
      phenotype. In this work, we have investigated the isolation of human articular
      chondrocytes from osteoarthritic (OA) cartilage at joint replacement, their
      expansion in monolayer culture, and their transduction with adenoviral,
      retroviral, and lentiviral vectors, using the gene encoding green fluorescent
      protein as a marker gene. The addition of growth factors (transforming growth
      factor beta(1), fibroblast growth factor 2, and platelet-derived growth factor
      BB) during cell culture was found to greatly increase cell proliferation and
      thereby to selectively enhance the efficiency of transduction with retrovirus.
      With adenoviral and lentiviral vectors the transduction efficiency achieved was
      95 and 85%, respectively. Using growth factor-supplemented medium with a
      retroviral vector, efficiency in excess of 80% was achieved. The expression was
      stable for several months with both retrovirus and lentivirus when analyzed by
      fluorescence-activated cell-sorting flow analysis and immunoblotting.
      Transduction with SOX9 was investigated as a method to reinitiate cartilage
      matrix gene expression in passaged human OA chondrocytes. Endogenous collagen II
      expression (both mRNA and protein) was increased in monolayer culture using both
      adenoviral and retroviral vectors. Furthermore, collagen II gene expression in
      chondrocytes retrovirally transduced with SOX9 was stimulated by alginate bead
      culture, whereas in control chondrocytes it was not. These results demonstrated
      methods for rapid expansion and highly efficient transduction of human OA
      chondrocytes and the potential for the recovery of key features of chondrocyte
      phenotype by transduction with SOX9.

PMID- 15165475
TI  - Cartilage-scaffold composites produced by bioresorbable beta-chitin sponge with
      cultured rabbit chondrocytes.
AB  - We newly produced bioresorbable beta-chitin sponge and used it as a scaffold for
      three-dimensional culture of chondrocytes. beta-Chitin was obtained from the pens
      of Loligo squid and the beta-chitin sponge was formed into a pillar shape. We
      produced cartilage-scaffold composites with a cartilage-like layer at the surface
      by culturing beta-chitin sponge-attached chondrocytes at the surface for 4 weeks.
      The mean DNA content at week 4 was 2.52-fold more than preculture DNA content.
      The mean concentration values of chondroitin sulfate and hydroxyproline continued
      to increase after week 2. Type II collagen and aggrecan genes were both found to
      be expressed during the experiment. Overall results of the biochemical analysis,
      along with histochemical and immunohistochemical findings and RT-PCR analysis,
      indicate that the cartilage-like layer in the chondrocyte-beta-chitin sponge
      composite was similar to hyaline cartilage. Electron microscopy scanning also
      revealed that the cell layer at the surface of the beta-chitin sponge was filled
      with chondrocytes and abundant extracellular matrix. beta-Chitin sponge can be
      considered biocompatible with chondrocytes, and an adequate scaffold for three
      dimensional chondrocyte culture. Because this technique can produce a pillar
      shaped composite, we will be able to press-fit the composites into articular
      cartilage defects without covering the periosteum or suturing the implant.

PMID- 15165476
TI  - Automatic algorithm for generating complex polyhedral scaffold structures for
      tissue engineering.
AB  - In this article, an approach for tissue-engineering (TE) scaffold fabrication by
      way of integrating computer-based medical imaging, computer graphics, data
      manipulation techniques, computer-aided design (CAD), and rapid prototyping (RP)
      technologies is introduced. The aim is to provide a generic solution for the
      production of scaffolds that can potentially meet the diverse requirements of TE
      applications. In the work presented, a novel parametric library of open
      polyhedral unit cells is developed to assist the user in designing the
      microarchitecture of the scaffold according to the requirements of its final TE
      application. Once an open polyhedral unit cell design is selected and sized, a
      specially developed algorithm is employed to assemble the microarchitecture of
      the scaffold while adhering to the external geometry of the patient's anatomy
      generated from medical imaging data. RP fabrication techniques are then employed
      to build the scaffolds according to the CAD-generated designs. The combined
      application of such technologies promises unprecedented scaffold qualities with
      spatially and anatomically accurate three-dimensional forms as well as highly
      consistent and reproducible microarchitectures. The integrated system also has
      great potential in providing new cost-effective and rapid solutions to customized
      made-to-order TE scaffold production.

PMID- 15165477
TI  - ProteinChip system technology: a powerful tool to analyze expression differences
      in tissue-engineered blood vessels.
AB  - At the time of implantation, tissue-engineered constructs should resemble native
      tissues as closely as possible. At present, histology and biochemical methods are
      commonly used to compare tissue-engineered constructs with native tissue. A
      ProteinChip system based on surface-enhanced laser desorption/ionization time of
      flight mass spectrometry (SELDI) has been developed that allows visualization of
      complex protein profiles from biological samples. The aim of this study was to
      determine whether the ProteinChip system is a suitable tool with which to compare
      the protein expression profiles of tissue-engineered aortic blood vessels with
      native tissues. Tissue-engineered blood vessel substitutes were fabricated with
      poly-4-hydroxybutyrate scaffolds, ovine vascular cell seeding, and dynamic tissue
      culture conditions. Engineered, ovine aortic, and carotid tissues were
      homogenized and total protein was extracted. Samples were analyzed on ProteinChip
      arrays. Analysis yielded reproducible protein profiles from all samples. About
      150 distinct protein peaks were detected. Comparative analysis with ProteinChip
      software revealed that the protein profiles from native aorta and native carotid
      arteries were similar whereas early tissue-engineered samples displayed more
      distinct deviations. In conclusion, ProteinChip system technology is rapid,
      reproducible, and highly sensitive in highlighting differentially expressed
      proteins in tissue-engineered blood vessel substitutes.

PMID- 15165478
TI  - Effects of high molecular weight hyaluronan on chondrocytes cultured within a
      resorbable gelatin sponge.
AB  - Freshly isolated bovine articular chondrocytes were seeded into a resorbable
      gelatin sponge and cultured in the absence or presence of extrinsic high
      molecular weight hyaluronan (HA) for up to 1 month. The gelatin sponge could be
      uniformly and reproducibly loaded with chondrocytes. Immunostaining demonstrated
      that accumulation of pericellular HA increased in the presence of extrinsic HA.
      However, this approach could not differentiate between extrinsic and endogenous
      HA. More chondrocytes were retained within the loaded sponges in the presence of
      HA. Both cell number and matrix synthesis were increased in the presence of high
      molecular weight HA throughout the time course. Proteoglycan synthesis per cell
      increased by 22-fold in the presence of HA at 500 microg/mL. Our model
      demonstrates that HA can be used as a tool not only to expand freshly isolated
      chondrocyte numbers but also to increase matrix synthesis and deposition within a
      resorbable gelatin sponge. Autologous chondrocytes for tissue engineering are
      always in short supply, so this could be a useful tool with which to increase the
      retention of cells seeded into other types of scaffold matrices before implanting
      them into a cartilage defect.

PMID- 15165479
TI  - Effects of basic fibroblast growth factor on the repair of large osteochondral
      defects of articular cartilage in rabbits: dose-response effects and long-term
      outcomes.
AB  - Articular cartilage possesses a limited capacity for self-renewal. The
      regenerated tissue often resembles fibrocartilage-like tissue rather than hyaline
      cartilage, and degeneration of the articular surface eventually occurs. The
      purpose of this study was to investigate the effect of basic fibroblast growth
      factor (bFGF) on the healing of full-thickness articular cartilage defects. bFGF
      (0, 10, 50, 100, 250, 500, or 1000 ng) was mixed with collagen gel and implanted
      into full-thickness articular cartilage defects drilled into rabbit knees. The
      repaired tissue was examined grossly and histologically, and was evaluated with
      the use of a grading scale at 4, 12, 24, and 50 weeks. At 4 weeks, treatment with
      100 ng of bFGF had greatly stimulated cartilage repair both grossly and
      histologically in comparison with untreated defects (those filled with plain
      collagen gel). The average total scores on the histological grading scale were
      significantly better for the defects treated with bFGF than for the untreated
      defects. These improvements were evident as long as 50 weeks postoperatively,
      although slight deterioration was noted in the repaired cartilage.
      Immunohistochemical staining for type II collagen showed that this cartilage
      specific collagen was diffusely distributed in the repaired tissue at 50 weeks.
      These findings suggest that bFGF may be a practical and important candidate for
      use in cartilage repair.

PMID- 15165480
TI  - Entrapment of migrating hippocampal neural cells in three-dimensional peptide
      nanofiber scaffold.
AB  - Isolation and expansion of self-renewing neural cells ex vivo are required for
      neural tissue repair in regenerative medicine. Neurogenesis occurs in restricted
      areas of postnatal mammalian brain including dentate gyrus and subventricular
      zone. We developed a simple method to entrap migrating neural cells (potential
      neuroprogenitors) from postnatal hippocampal organotypic cultures in three
      dimensional (3-D) peptide nanofiber scaffolds. A few hours after placing the
      hippocampal slices in culture, cell proliferation activity at the "interface
      zone" between the tissue slice and the membrane culture surface was observed.
      Pulse-chase experiments using 5-bromodeoxyuridine (BrdU), which measures mitotic
      activity, showed that a number of cells incorporated BrdU at the interface zone.
      The number of BrdU(+) cells increased exponentially during the first 3 days of
      exposure to the label. The BrdU(+) cells also stained positive for glial
      fibrillary acidic protein (2.2 +/- 0.5%), a marker for astroglia; and for betaIII
      tubulin (7.3 +/- 2.8%) and nestin (2.7 +/- 0.9%), markers for neural progenitors.
      When hippocampal slices were cultured on a peptide nanofiber scaffold layer (~500
      microm thick), a more extended interface zone between each tissue slice and the
      scaffold was formed. Moreover, the migrating BrdU(+) cell population entrapped in
      the 3-D peptide scaffold was readily isolated by mechanically disrupting the
      scaffold and then used for conventional 2-D culture systems for further studies.
      This simple method may be useful not only in developing technology for neural
      progenitor cell isolation and enrichment in vitro, but also for expanding cells
      for cell-based therapies of regenerative medicine.

PMID- 15165481
TI  - HLA-DR antigen and bax protein expression in patients with primary non-Hodgkin's
      gastric lymphoma.
AB  - Primary gastric lymphoma represents a rare gastrointestinal malignancy with an
      unclear prognosis. The aim of this study was to determine the prognostic
      significance of HLA-DR antigen and bax expression in patients with primary non
      Hodgkin's gastric lymphoma. We immunohistochemically studied bax protein and HLA
      DR antigen expression in 36 B-cell, MALT-type primary gastric lymphoma patients
      diagnosed and treated in our department from 1990 to 1995. Ten non-malignant
      gastric tissue specimens were used as benign controls. Clinicopathological and
      survival data were correlated with the staining results. HLA-DR antigen
      expression was observed in 33 gastric lymphoma patients (91.7%). Positive bax
      staining was found in 24 gastric lymphomas (66.7%) and in none of the benign
      cases studied. In the univariate analysis, those gastric lymphoma patients who
      expressed HLA-DR antigen in more than 15% of their tumor cells, presented a
      significantly improved 5-year survival rate (75% vs. 37.5%, p = 0.04).
      Furthermore, gastric lymphoma patients who were bax(+)/HLA-DR(+) had a
      statistically better overall survival compared to those who were bax(-)/HLA-DR(-)
      (82.4% vs. 25%, p = 0.01). HLA-DR antigen expression was associated with a
      favorable clinical outcome. Its expression improved the predictive value of bax
      protein expression in non-Hodgkin's gastric lymphoma patients. The combined use
      of these markers permits the identification of a high-risk group of patients that
      may benefit from a more aggressive therapeutic approach.

PMID- 15165482
TI  - Mapping of SOMU1 and M1 epitopes on the apomucin encoded by the 5' end of the
      MUC5AC gene.
AB  - We have developed 11 monoclonal antibodies (MAbs) against human gastric mucin, (1
      13M1, 2-11M1, 2-12M1, 9-13M1, 58M1, 19M1, 21M1, 45M1, 463M, 589M, 62M1), which
      specifically stained by immunohistochemisty both the human gastric surface mucosa
      and colon adenoma. Among them, five (19M1, 21M1, 463M, 589M, 62M1) immunoreacted
      with the peptide encoded by the 3' region of the MUC5AC gene (Nollet et al: Int J
      Cancer 2002;99:336-343). In this study, we identified in the 5' region of this
      gene the nucleotide fragments encoding peptides immunoreacting with three other
      anti-M1 MAbs (1-13M1, 2-11M1 and 9-13M1), as well as the SOMU1 MAb (Sotozono et
      al: J Immunol Methods 1996;192:187-196). 1-13M1 MAb immunoreacts with peptides,
      including the Cys 2 and Cys 4 domains. The SOMU1 MAb recognized the Cys 5 domain,
      and the MAbs 2-11M1 and 9-13M1 the globular D1/D2 and D3 domains, respectively.
      Using serial sections of the mucosae adjacent to colon adenocarcinomas and colon
      adenomas, we observed that the anti-M1 and anti-SOMU1 MAbs displayed the same
      immunostaining patterns. The three anti-M1 MAbs (2-12M1, 58M1, and 45M1) did not
      react with the products of the MUC5AC gene tested until now. The MUC5AC apomucin
      is now well characterized by MAbs immunoreacting against seven different epitopes
      belonging to the different main cystein globular domains of this macromolecule.
      Such antibodies are useful tools for studying the biosynthesis, polymerization,
      and degradation of mucin.

PMID- 15165483
TI  - Identification of cross-reactive and restricted epitopes localized on human
      chorionic gonadotropin beta-subunit by monoclonal antibodies.
AB  - Human chorionic gonadotropin (hCG) belongs to the family of glycoprotein
      hormones. All members of the family are composed of an identical alpha subunit
      and structurally related beta subunit which confers biological specificity.
      Specific quantification and functional analysis of hCG require the use of
      monoclonal antibodies recognizing different epitopes of hCGbeta. This study
      describes the production and characterization of monoclonal antibodies (MAbs) to
      hCGbeta with no cross-reactivity to other glycoprotein hormones. Spleen cells
      from Balb/c mice immunized with hCG were fused with mouse SP2/0 myeloma cells.
      Fused cells were grown in hypoxanthine, aminopterine, and thymidine (HAT)
      selective medium and cloned by limiting dilution assay. Antibody-secreting cells
      were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of
      secreted MAbs was further analyzed, using a panel of highly purified and
      recombinant glycoprotein hormones, their subunits and peptides representing the C
      terminal end of hCGbeta (hCGbeta-CTP) by ELISA and immunoblotting. The affinity
      constant (K(aff)) was also determined by ELISA. Three murine hybridomas
      designated G5M1, B12M2 and F4M3 were obtained that secrete MAbs specific for
      hCGbeta. The G5M1 MAb reacts only with hCGbeta, hCGbeta-CTP and intact hCG with
      no detectable cross-reaction with hCGalpha or any of the other glycoprotein
      hormones. The specificity of B12M2 MAb is very similar to G5M1, but it does not
      react with hCGbeta-CTP. The F4M3 MAb also has similar specificity to G5M1 and
      B12M2, but it strongly cross-reacts with hLH. The affinity constant (Kaff) of
      G5M1, B12M2 and F4M3 was found to be 4.28 x 10(9), 5.2 x 10(8), and 1.97 x 10(9)
      M(-1), respectively. Our results indicate that G5M1 and B12M2 MAbs are specific
      for hCG and recognize epitopes restricted to hCGbeta, but F4M3 recognizes a
      common epitope expressed both on hCGbeta and hLHbeta.

PMID- 15165484
TI  - Establishment and evaluation of cancer-specific human monoclonal antibody GAH for
      targeting chemotherapy using immunoliposomes.
AB  - To establish human monoclonal antibodies suitable for targeting chemotherapy, we
      prepared a panel of human-mouse hybridomas, using mouse myelomas and lymphocytes
      of regional lymph nodes excised from cancer patients, and selected antibodies on
      the basis of their specificity of binding to the surface of viable cancer cells
      derived from fresh cancer tissues. A selected antibody, named GAH, was found to
      react with viable cancer cells from 21/22 stomach and 13/20 colon cancer tissues.
      As for further analysis, complementary DNAs encoding GAH were cloned and
      recombinant GAH (rGAH) was obtained from established CHO cells transfected with
      GAH expression vectors. rGAH selectively stained cancer cells in human tissue
      sections from 13/14 stomach, 4/11 colon, 5/11 mammary, and 0/7 lung cancers,
      while no positive staining was observed in those of non-tumor and various normal
      specimens. Notably, using confocal fluorescence microscopy, rGAH was not only
      bound to the surface of cancer cells, but was also internalized by the cells. The
      potential of rGAH for intracellular drug delivery was subsequently evaluated
      using rGAH-conjugated, doxorubicin (DXR)-encapsulated immunoliposomes. The
      immunoliposomes were also internalized into the cancer cells and finally DXR was
      delivered to the cell nucleus. Furthermore, the immunoliposomes could inhibit the
      growth of DXR-insensitive stomach cancer cells (B37) in an in vivo model. These
      results suggest that a GAH-utilized liposome-targeting technique will provide a
      potent and useful cancer chemotherapy with broad applications for cancer
      patients.

PMID- 15165485
TI  - Generation and characterization of monoclonal antibodies directed against the
      surface antigens of cervical cancer cells.
AB  - In this report, we describe the development and characterization of monoclonal
      antibodies against the surface antigens of cervical cancer cells. Using HeLa
      cervical carcinoma cells as the immunogen, we have developed a number of
      antibodies that specifically label cervical cancer cells but not normal cervical
      epithelial cells. These antibodies displayed differential reactivity towards
      various cervical cancer cell lines as determined by immunofluorescence labeling
      and western blotting analyses. One of these antibodies, 13G4, which showed the
      strongest labeling to HeLa cells and has the widest range of reactivity to other
      cervical cancer cell lines, was extensively characterized. By immunoaffinity
      chromatography, we purified a 90-kDa protein that appears to be the principal
      target recognized by this antibody. This protein was subsequently identified as
      decay accelerating factor (DAF) or CD55 by the mass spec sequencing analysis of
      the tryptic peptides derived from this protein. Digestion of HeLa DAF with
      glycosidases that removed its N- and O-linked carbohydrates has revealed that the
      13G4 antibody binds to the peptide portion of this glycoprotein. Overall, our
      approach of generating and characterizing monoclonal antibodies directed against
      the surface antigens of cervical cancer cells serves as a stepping stone towards
      the eventual development of a unique panel of monoclonal antibodies that could
      potentially be used for the detection and therapeutic treatment of cervical
      cancer.

PMID- 15165486
TI  - Production of monoclonal antibodies against canine leukocytes.
AB  - A panel of anti-canine leukocyte monoclonal antibodies (MAbs) was produced by
      immunizing BALB/c mice with canine peripheral blood mononuclear cells (PBMC),
      either resting or stimulated with concanavalin A (ConA). Three out of 28 clones
      IH1, AB6, and HG6-screened by ELISA and producing antibody with the highest
      specificity for canine cell immunostaining, were subjected to three subsequent
      subcloning steps by limiting dilution, and selected for further characterization.
      These MAbs belonged to IgG1 (HG6 and IH1) and IgG2a (AB6) isotypes. The
      distribution of cell populations expressing the antigen recognized by the
      antibodies was identified by indirect immunoflorescence on canine PBMC and on
      tissue sections of lymph node, spleen, liver and skin. The possible
      crossreactivity with human PBMC was also examined in immunocytochemistry. One of
      the antibodies specifically recognized macrophages. The MAbs presented here can
      be foreseen as possible valuable diagnostic and research tools to study immune
      functions in dogs.

PMID- 15165487
TI  - Production of monoclonal antibodies against a 19-kD recombinant Plasmodium vivax
      MSP1 for detection of P. vivax malaria in Turkey.
AB  - Plasmodium vivax malaria, which is transmitted to humans by mosquitoes, is one of
      the most important parasitic diseases in Turkey. The major protein on the surface
      of asexual erythrocytic stage merozoites of P. vivax (Pv) is 200 kD and called
      major merozoite surface protein-1 (PvMSP1). Polyclonal antibodies against the 19
      kD C-terminal fragment of PvMSP1 (PvMSP1(19)) are protective in monkey models of
      P. vivax and associated with protection in field studies. In this research,
      monoclonal antibodies were produced against PvMSP1(19). A total of 214 IgG(1)
      antibody-releasing hybridomas were obtained and three monoclonal antibodies were
      produced (PvMSP1(19).1, PvMSP1(19).2, and PvMSP1(19).3) and selected for further
      study. They have now been purified from ascitic fluid on a Staphylococcus protein
      A affinity column. These are the first monoclonal antibodies produced against P.
      vivax in Turkey and the first monoclonal antibodies produced against this
      recombinant PvMSP1(19) in the world. The monoclonal antibodies will be used to
      study the epidemiology of P. vivax in patients with malaria in Turkey, and to
      develop better strategies for early diagnosis and treatment of the disease in our
      population.

PMID- 15165496
TI  - Optimal healing environments and integrative cancer therapy.

PMID- 15165497
TI  - Role of omega-3 fatty acid supplementation in inflammation and malignancy.
AB  - Omega-3 fatty acids (FAs), which include eicosapentaenoic acid (EPA) and
      docosahexaenoic acid, are found in fish oils and have long been investigated as
      components of therapy for various disease states. Population studies initially
      revealed the cardioprotective and anti-inflammatory effects of omega-3 FAs and
      EPA, with subsequent clinical studies supporting the therapeutic role of omega-3
      FAs in cardiovascular and chronic inflammatory conditions. Prospective randomized
      placebo-controlled trials have also demonstrated the utility of omega-3 FA
      supplementation in malignancy and cancer cachexia. In recent years, in vitro and
      animal studies have elucidated some of the mechanistic explanations underlying
      the wide range of biological effects produced by omega-3 FAs and EPA, including
      their antiproliferative and anticachectic actions in malignancy. In this review,
      the authors discuss the recent progress made with omega-3 FAs, focusing on the
      advances in mechanistic understanding and the results of clinical trials.

PMID- 15165498
TI  - The challenges of randomized trials in integrative cancer care.

PMID- 15165499
TI  - Safety and efficacy of herbal sedatives in cancer care.
AB  - Insomnia and other sleep disturbances are common in cancer patients. Insomnia is
      a multifactorial health concern that currently affects at least 1 in 3 cancer
      patients, and yet most insomnia sufferers do not consult their physician
      regarding pharmaceutical options for relief. Use of hypnotic drugs (primarily
      benzodiazepines) is associated with increasing tolerance, dependence, and adverse
      effects on the central nervous system. While hypnotic drug use declined
      substantially in the past decade, the use of herbal sedatives appeared to
      increase. Mostly self-prescribed by lay people, herbal sedatives hold widespread
      appeal, presumably because of their lower cost and higher margin of safety when
      compared to pharmaceuticals. Studies of better-known herbal sedatives, notably
      valerian and kava, showed moderate evidence for both safety and efficacy for
      valerian while revealing disturbing toxicity concerns for kava. Milder sedatives
      or anxiolytics in need of clinical study include German chamomile, lavender,
      hops, lemon balm, and passionflower; St. John's wort may have anxiolytic effects
      with relevance to sleep. Herb-drug interactions are a possibility for some of
      these species, including St. John's wort. Although sufficient evidence exists to
      recommend some of these agents for short-term relief of mild insomnia, long-term
      trials and observational studies are needed to establish the safety of prolonged
      use as well as overall efficacy in the context of cancer treatment and
      management.

PMID- 15165500
TI  - Integrative tumor board: glioblastoma multiforme.

PMID- 15165505
TI  - Cancer and complementary and alternative medicine in Italy: personal observations
      and historical considerations.
AB  - This article contains observations and historical considerations on cancer and
      complementary and alternative medicine (CAM) in Italy, a country that has a great
      tradition in medical research, going back to the Renaissance. However, Italy does
      not have a strong tradition of using CAM approaches in the treatment of cancer.
      While surveys show that the Italian population is eager to learn more about CAM,
      the medical profession there is largely dismissive of these methods. In 1997
      1998, the notorious Luigi Di Bella affair occurred in Italy, when a professor of
      physiology at Modena proposed a nonconventional approach to cancer treatment,
      based on the off-label use of somatostatin. This treatment found champions in the
      media and general public but was opposed by most of the medical profession.
      Although clinical trials later demonstrated that it had no efficacy, the affair
      divided Italian public opinion and nearly brought down the national government.
      Italy no longer has prominent proponents of nonconventional treatments in cancer.
      However, it continues to have innovative scientists who do important work that is
      consonant with a CAM approach. This article considers the work of 3 such
      scientists: Paolo Lissoni, MD, of Monza (Milan), who has carried out numerous
      clinical trials with the pineal hormone melatonin; Giancarlo Pizza, MD, of
      Bologna, who has done extensive work on the use of transfer factor and other
      immunomodulators in the treatment of renal cell and other kinds of cancer; and
      Aldo Mancini, MD, of Naples, who has isolated a mutated form of Mn-SOD-2 from the
      growth medium of a unique liposarcoma cell line. These scientists have introduced
      some flexibility into a rigid state-run hospital system by offering patients
      innovative treatment options in the context of approved clinical trials.

PMID- 15165506
TI  - An interview with Doriano Fabbro, Ph.D., Novartis Biomedical Research Institute.
      Interviewed by Vicki Glaser.

PMID- 15165507
TI  - An interview with Paul England, Ph.D., ProXara Biotechnology, Ltd. Interviewed by
      Vicki Glaser.

PMID- 15165508
TI  - Comparison of on-chip and off-chip microfluidic kinase assay formats.
AB  - Kinases represent an important class of targets for pharmaceutical drug
      development. Microfluidic devices capable of running kinase assays with either an
      on-chip or an off-chip enzymatic reaction have been developed. For the on-chip
      assay, reagent addition, mixing, enzymatic reaction, and electrophoretic
      separation and detection of substrate and product all take place in the channels
      of the microfluidic chip. For the off-chip assay, the reaction takes place in a
      microtiter plate, whereas the electrophoretic separation and detection of
      substrate and product take place in the channels of the chip. To probe
      differences between the on-chip and off-chip assays, a panel of commercially
      available kinase inhibitors was assayed at 10 microM against cyclic AMP-dependent
      protein kinase A, glycogen synthase kinase 3beta, mitogen- and stress-activated
      protein kinase, and Akt1 using both the off-chip and on-chip assays. Good
      correlation was observed between inhibition measured by the two methods, with
      most of the differences in measured inhibition being attributed to compound
      solubility and enzyme concentration effects. Microfluidic devices represent an
      attractive platform for kinase assays due to high data quality and the
      possibility of on-chip assay integration, leading to reagent and labor savings.

PMID- 15165509
TI  - Substrate capacity considerations in developing kinase assays.
AB  - In developing a screening assay for a serine/threonine kinase, we evaluated
      various formats of an in-plate enzyme-linked immunosorbent assay (ELISA), as well
      as solution-phase kinase assays using either ELISA or AlphaScreen detection.
      Substrate was available both as a biotinylated 15-residue peptide and as a 25
      residue peptide containing the same sequence expressed as a glutathione S
      transferase fusion protein. When increasing concentrations of either of these
      substrates were coated directly onto ELISA plates, the rates of the kinase
      reactions progressively increased. In contrast, when the biotin-peptide was
      captured onto NeutrAvidin-coated plates, the finite peptide binding capacity of
      the plates limited the amount of substrate that could be incorporated into the
      assay system and thereby limited the rate of the reaction at a given kinase
      concentration. Solution-phase kinase reactions can tolerate high substrate
      concentrations; however, analysis of kinase reaction samples containing biotin
      peptide concentrations higher than the binding capacity of NeutrAvidin-coated
      plates resulted in an inability to detect differences between reactions run at
      different substrate concentrations. For AlphaScreen detection following solution
      phase kinase reactions, limitations in the binding capacity of the donor and
      acceptor beads caused loss of signal for substrate concentrations above the
      maximum binding capacity. Overall, the solution-phase assays required
      significantly more kinase than the in-plate assays (1-4 microg/ml versus <100
      ng/ml, respectively). These studies demonstrate that the amount of substrate that
      can be incorporated into an assay system substantially affects the rate of the
      kinase reaction and therefore the amount of kinase required for the assay.

PMID- 15165510
TI  - Miniaturized, ultra-high throughput screening of tyrosine kinases using
      homogeneous, competitive fluorescence immunoassays.
AB  - Assay miniaturization and the implementation of high-density 1,536-microwell
      screening increase the speed and efficiency of screening and lead discovery. To
      serve this need, a platform of miniaturizable assay technologies has been
      assembled for specific biological targets. This platform will enable initiation
      and completion of uHTS screens in a straightforward and expeditious manner.
      Although faster primary screening does contribute to a reduction in timelines,
      the process of assay development can become a bottleneck. Assay technologies that
      do not require the use of target-specific reagents can reduce the time necessary
      for assay development. Assays that measure inhibition of tyrosine kinases can be
      configured in a competitive format where only the enzyme itself is specific to
      the assay. In this context, several technologies, including time-resolved
      fluorometry (also known as DELFIA), time-resolved fluorescence resonance energy
      transfer (also known as LANCE( trade mark )), fluorescence polarization, enzyme
      fragmentation complementation assay, and confocal laser scanning imaging, were
      examined. Quality parameters such as assay reproducibility, signal:background
      ratio, Z factor, and assay sensitivity were compared. Additionally, the relative
      merits of each of these technologies are assessed in terms of assay
      miniaturization, ease of development, ultimate screening capability, efficiency,
      and cost.

PMID- 15165511
TI  - High-throughput screening with quantitation of ATP consumption: a universal non
      radioisotope, homogeneous assay for protein kinase.
AB  - A number of assays have been developed for high-throughput screening (HTS) of
      potentially bioactive compounds. To screen millions of chemical compounds
      efficiently, the best detection technology prior to initiating HTS must be
      chosen. Ideally, a non-radioisotope (non-RI), homogeneous method, equivalent to
      the most reliable assay for a particular target, should be selected as an HTS
      method. Protein kinases are among the most important classes for drug discovery
      because they participate in various signaling pathways. Several HTS technologies
      are available for kinase activity: SPA (Amersham, Piscataway, NJ, U.S.A.), HTRF
      (CIS-US, Inc., Bedford, MA, U.S.A.), IMAP (Molecular Devices, Sunnyvale, CA,
      U.S.A.), and Z'-LYTE (Invitrogen, Carlsbad, CA, U.S.A.). The amount of
      phosphorylated product is detected by different methods in these assays.
      Recently, Kinase-Glo Luminescent Kinase Assay, a non-RI, homogeneous, adenosine
      triphosphate (ATP) quantitative kit useful for kinase activity detection, has
      become available from Promega (Madison, WI, U.S.A.). ATP is a universal substrate
      for kinases. Thus, the Kinase-Glo assay shows promise for becoming the primary
      method of determining kinase activity in HTS. We have developed a Kinase-Glo
      system for cyclin-dependent kinase 4 (Cdk4), and compare its results with those
      of the filtration method, the most reliable assay for in vitro Cdk4 activity. In
      addition, the reliability and sensitivity of the Kinase-Glo are discussed.

PMID- 15165512
TI  - Identification of kinase inhibitors by an ATP depletion method.
AB  - ATP is one of the substrates of luciferase. ATP concentrations can be measured by
      quantitating the light output from a luciferase reaction. As kinases also use
      ATP, it is possible to assay kinase activity through the loss of luminescence in
      a coupled luciferase reaction. We have applied this luminescence-based ATP
      depletion approach to a model serine/threonine kinase. We find that the method
      may be run as an endpoint assay, in which ATP detection reagents (containing
      luciferase and luciferin) are added at the end of the reaction, or in a kinetic
      mode, where the ATP detection reagents are present throughout the reaction. The
      ATP depletion approach is capable of detecting kinase inhibitors. Six inhibitors
      of the model kinase, previously identified using other screening methods, are
      also active in the luminescence-based approach and display a similar rank order
      of potency. An advantage of the method is that kinase inhibitors, because they
      increase luminescence (by reversing the enzyme-dependent loss of signal), are
      immediately distinguishable from compounds such as luciferase inhibitors and
      luminescence quenchers, which further reduce the luminescence. The compound
      collections that we screened were rich in compounds that reduced luminescence.
      Compounds that have dual kinase and luciferase inhibitory activity, or kinase
      inhibitory activity combined with luminescence quenching, might be missed by
      being classified as false negatives. We show that the kinetic form of the assay
      can be used to minimize this possibility.

PMID- 15165513
TI  - Development and validation of a fluorescence technology for both primary and
      secondary screening of kinases that facilitates compound selectivity and site
      specific inhibitor determination.
AB  - The IQ Technology has been developed to serve as a homogeneous, universal
      detection platform for HTS of kinases and phosphatases. The technology is a
      direct, noncompetitive assay format that does not require antibodies or
      radioactive reagents to measure phosphorylation state. Fluorophore-labeled
      peptides are used as enzyme substrates, and kinase or phosphatase activity is
      quantitated by direct measurement of the phosphorylation state of the substrate.
      Phosphorylation is measured by the change in fluorescence intensity that occurs
      when a proprietary iron-containing compound binds specifically to phosphoryl
      groups on peptides. This change in observed fluorescence is proportional to the
      extent of phosphorylation of the fluorophore-labeled peptide. The technology
      provides a universal method that can be used with any peptide sequence and is
      insensitive to high concentrations of ATP. Inhibition at the ATP-binding site
      versus the phosphorylation site can be differentiated and compound selectivity
      identified using the same detection method as in the primary screen. The
      technology has been tested against a large number of detergents, organics, and
      other reagents found in reaction mixtures, and the detection method eliminates
      common issues associated with fluorescent and chromogenic compounds. The
      technology has been formatted for 96-, 384-, and 1,536-well microplate formats,
      and a representative Z' value of 0.7 was obtained. IC(50) values generated using
      this platform correlate with previously reported values, and screening of a small
      compound library was performed to evaluate the assay further.

PMID- 15165514
TI  - Applications of fluorescent polymer superquenching to high throughput screening
      assays for protein kinases.
AB  - Protein kinases are involved in the regulation of cellular metabolism, growth,
      differentiation, and proliferation. Aberrations in their function can lead to
      diseases such as cancer and inflammation. Protein kinases are therefore possible
      targets for drug therapies. To address the need for high throughput screening of
      potential inhibitors, QTL has developed a homogeneous and robust kinase assay for
      use in multiwell plate format. The QTL Lightspeed fluorescence superquenching
      based kinase assays do not require specialized equipment, nor do they involve the
      use of radioactive hazardous materials or antibodies. QTL Lightspeed kinase
      assays directly measure the enzymatic activity of the target and do not involve
      secondary (detector) enzyme. In this article, we compare QTL Lightspeed protein
      kinase assays using Protein Kinase A, Protein Kinase Balpha/Akt1, and ribosomal
      S6 kinase-2 as examples with other commercially available kinase kits. Our data
      show that QTL Lightspeed kinase assays offer significant advantages over the
      current commercial kits in terms of both sensitivity and performance. The QTL
      Lightspeed kinase assay also offers a kinetic assay mode where the substrate
      phosphorylation can be monitored in real-time.

PMID- 15165515
TI  - Overcoming compound interference in fluorescence polarization-based kinase assays
      using far-red tracers.
AB  - Kinase-mediated phosphorylation of proteins is critical to the regulation of many
      biological processes, including cell growth, apoptosis, and differentiation.
      Because of the central role that kinases play in processes that can lead to
      disease states, the targeting of kinases with small-molecule inhibitors is a
      validated strategy for therapeutic intervention. Classic methods for assaying
      kinases include nonhomogenous enzyme-linked immunosorbent assays or scintillation
      based formats using [gamma-(32)P]ATP. However, homogenous fluorescence-based
      assays have gained in popularity in recent years due to decreased costs in
      reagent usage through miniaturization, increased throughput, and avoidance of
      regulatory costs associated with the use of radiation. Whereas the readout signal
      from a nonhomogenous or radioactive assay is largely impervious to interferences
      from matrix components (such as library compounds), all homogenous fluorescent
      assay formats are subject to such interferences. Interference from intrinsically
      fluorescent compounds or from scattered light due to precipitated compounds can
      interfere with assays that depend on a fluorescence intensity (or fluorescence
      quenching), fluorescence resonance energy transfer, or fluorescence polarization
      based readout. Because these interfering factors show a greater effect at lower
      wavelengths, one strategy to overcome such interferences is to develop
      fluorescent assays using longer wavelength (red-shifted) fluorescent probes. In
      this article, we describe the PanVera PolarScreen far-red fluorescence
      polarization assay format, which mitigates assay interference from
      autofluorescent compounds or scattered light through the use of a far-red tracer.
      The tracer shows substantially less interference from light scatter or
      autofluorescent library compounds than do fluorescein-based tracers, and gives
      rise to a larger assay window than the popular far-red fluorophore Cy5.

PMID- 15165516
TI  - Immobilized metal ion affinity-based fluorescence polarization (IMAP): advances
      in kinase screening.
AB  - The IMAP Fluorescence Polarization technology is a homogeneous antibody-free
      method for analysis of kinases, phosphatases, and phosphodiesterases. Recent
      developments to the technology include an enhancement of the reagent system (the
      Progressive Binding System) that significantly expands the range of useable
      concentrations of ATP, choices of substrates, and assay configurations. With the
      new Progressive System, we are able to design multiplexed assays that allow the
      simultaneous determination of multiple kinase activities. In addition, coupled
      assays are now possible, allowing the assay of kinases through natural or
      artificial coupling through kinase cascades.

PMID- 15165517
TI  - Evaluation of kinase inhibitor selectivity by chemical proteomics.
AB  - Small-molecule inhibitors of protein kinases constitute a novel class of drugs
      for therapeutic intervention in a variety of human diseases. Most of these agents
      target the relatively conserved ATP-binding site of protein kinases and have only
      been tested against a rather small subset of all human protein kinases.
      Therefore, the selectivity of protein kinase inhibitors has remained a widely
      underestimated, but highly important issue in drug development programs. In this
      review, we focus on the recent advancement of chemical proteomic methods to
      evaluate drug selectivity in an unbiased, comprehensive way. Efficient affinity
      purification procedures using immobilized kinase inhibitors combined with the
      sensitivity of mass spectrometry detection permit the mapping of drug targets on
      a proteome-wide scale. Data from this type of assessment can be used to set up
      tailor-made selectivity panels, which guide compound development in the context
      of the most relevant off-targets during lead optimization. In cases in which
      identified alternative targets are of validated clinical relevance, chemical
      proteomics provides the opportunity to repeatedly exploit a once established
      kinase inhibitor principle for additional target kinases and can thereby
      dramatically shorten the time toward highly selective, preclinical candidates.
      Moreover, the identification of alternative targets for preclinical or clinical
      drugs can provide new insights into their cellular modes of action, which might
      help to define those disease settings in which the most beneficial therapeutic
      effect is likely to occur.

PMID- 15165518
TI  - Assessing cellular protein phosphorylation: high throughput drug discovery
      technologies.
AB  - Changes in protein phosphorylation mediate much of cellular physiology.
      Perturbations in the activity of the kinases that catalyze these reactions
      underlie numerous human pathologies, including metabolic and inflammatory
      disorders and most notably, cancer. HTS techniques that determine the activity of
      protein kinases in vitro are useful in the development of small molecule kinase
      inhibitors, but do not address underlying mechanistic concerns or efficient in
      vivo targeting. Observing protein phosphorylation in cell lysates and fixed cells
      in a high throughput manner is fundamental to understanding the mechanism of
      action of lead molecules and whether they target signaling pathways of interest.
      Herein we discuss several higher throughput techniques to study cellular protein
      kinase signal transduction and the strategies for implementation in kinase drug
      discovery.

PMID- 15165525
TI  - Auto-CPAP or constant CPAP? The patient knows what's best!

PMID- 15165526
TI  - The legacy of Karl-Axel Ekbom.

PMID- 15165527
TI  - What in sleep is for memory.
AB  - Since the seminal research by Jenkins and Dallenbach in the 1920s, it has been
      well proven that sleep has a major effect on the memory of pre-sleep material.
      However, there is still sparse knowledge about exactly which features of sleep
      have the most impact. Studies which examined separately the role of non-rapid eye
      movement (NREM) sleep and rapid eye movement (REM) sleep provided largely
      controversial results and aroused harsh scientific debate, and the investigation
      of the link of specific sleep patterns to different memory systems (e.g.
      declarative vs. procedural) did not fully reconcile these inconsistencies. New
      research perspectives have been proposed in recent years to overcome the limits
      of the previous 'single state' approach. Psychological, neurophysiological and
      neuroanatomical data have recently suggested that NREM and REM sleep both play a
      part in memory consolidation. We here present the hypothesis that NREM and REM
      are complementary for memory processes during sleep, thanks to their close
      interaction within the NREM-REM cycle, and discuss experimental data which prove
      the critical role of the sleep cycle for the morning recall of verbal material.

PMID- 15165528
TI  - The treatment of restless legs syndrome with intravenous iron dextran.
AB  - BACKGROUND AND PURPOSE: To evaluate the safety and efficacy of a single 1000 mg
      iron infusion in treating Restless Legs Syndrome (RLS). PATIENTS AND METHODS: A
      single 1000 mg intravenous (IV) [Am J Med Sci 31 (1999) 213] infusion of iron
      dextran was evaluated in an open-label study. Primary outcomes of efficacy were
      symptom severity assessed by global rating scale and periodic leg movements in
      sleep (PLMS) at 2 weeks post-infusion. Secondary outcomes included total sleep
      time (TST), hours/day of RLS symptoms, and changes in magnetic resonance imaging
      (MRI)-determined iron concentrations in the substantia nigra. Primary safety
      measures were reported adverse events and monthly serum ferritin levels. RESULTS:
      IV iron therapy significantly improved the mean global RLS symptom severity, TST,
      hours with RLS symptoms and PLMS, but on an individual basis failed to produce
      any response in 3 of the 10 subjects who were fully treated. Brian iron
      concentrations at 2 weeks post-infusion as determined by MRI were increased in
      the substantia nigra and prefrontal cortex. Serum ferritin levels showed a
      greater than predicted rapid linear decrease. Side effects were mild, except in
      one subject who developed an acute allergic reaction. CONCLUSIONS: The results in
      this study provide valuable information for future studies, but the efficacy and
      safety of IV iron treatment for RLS remain to be established in double-blind
      studies. The serum ferritin results suggest that greater than expected iron loss
      occurs after IV iron loading.

PMID- 15165529
TI  - Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care
      population: the REST (RLS epidemiology, symptoms, and treatment) primary care
      study.
AB  - OBJECTIVES: To assess the frequency, impact, and medical response to the restless
      legs syndrome (RLS) in a large multi-national primary care population. METHOD:
      Questionnaire surveys of matched patients and primary care physicians (PCPs) in
      five modern industrialized western countries. RESULTS: An RLS screening
      questionnaire was completed by 23,052 patients: 2223 (9.6%) reported weekly RLS
      symptoms; 1557 of these patients had medical follow-up questionnaires completed
      both by themselves and by their physician. An RLS sufferer subgroup (n=551)
      likely warranting treatment was defined as reporting at least twice weekly
      symptoms with appreciable negative impact on quality of life. A total of 88.4% of
      RLS sufferers reported at least one sleep-related symptom. Most reported impaired
      sleep consistent with a diagnosis of insomnia. Out of 551 sufferers, 357 (64.8%)
      reported consulting a physician about their RLS symptoms, but only 46 of these
      357 (12.9%) reported having been given a diagnosis. PCPs reported that 209
      (37.9%) RLS sufferers consulted them about RLS symptoms, but only 52 (24.9%) were
      given an RLS diagnosis. In most countries, sufferers, regardless of diagnosis,
      were prescribed therapies not known to be effective in RLS. CONCLUSIONS: RLS
      significantly impairs patients' lives, often by severely disrupting sleep. The
      marked under-diagnosis and inappropriate treatment of RLS indicates that PCPs
      need better education about this condition. Recognizing how often disrupted sleep
      results from RLS should improve diagnosis.

PMID- 15165530
TI  - Preference for fixed or automatic CPAP in patients with obstructive sleep apnea
      syndrome.
AB  - BACKGROUND: The aims of this study were to compare compliance to treatment with
      fixed CPAP and with autoCPAP, subjective preference for type of CPAP treatment,
      and factors associated to preference for autoCPAP in patients with OSAS. PATIENTS
      AND METHODS: Twenty-two subjects were studied in a randomized, single blind cross
      over fashion. They were treated for one month by fixed CPAP (Elite Sullivan V,
      ResMed, Sydney, Australia) and one month by autoCPAP (Autoset T, ResMed, Sydney,
      Australia). RESULTS: Four subjects who stated a preference for fixed CPAP and
      four who expressed no preference were pooled together; fourteen preferred
      autoCPAP. Compliance to treatment using the two machines did not differ in the
      first group (3.8 (1.9) vs. 3.8 (1.5)h/day, fixed vs autoCPAP), but was higher
      with autoCPAP in the second group (4.8 (1.8) vs 5.5 (1.5)h/day, P<0.05). Baseline
      apnea/hypopnea index (AHI) was high in both groups, but was higher in the second
      group P<0.02. First treatment was always fixed CPAP in patients who preferred
      fixed CPAP, while it was either in the other subjects. CONCLUSIONS: Compliance to
      autoCPAP differs among OSAS patients. As long as factors predicting higher
      compliance to autoCPAP are not found, a trial with autoCPAP in patients poorly
      compliant to fixed CPAP may be warranted.

PMID- 15165531
TI  - Psychiatric symptoms in children with insomnia referred to a pediatric sleep
      medicine center.
AB  - BACKGROUND AND PURPOSE: To assess the frequency and nature of clinical and
      psychiatric symptoms in children referred to a pediatric sleep center for
      evaluation of insomnia. PATIENTS AND METHODS: A retrospective chart review of all
      children referred to the pediatric sleep medicine was conducted. Children
      presenting exclusively with sleep initiation and/or maintenance problems
      underwent a structured clinical psychiatric interview and their parents completed
      the behavioral assessment system for children (BASC), pediatric symptom
      checklist, the clinical attention problem scale and a detailed sleep
      questionnaire. RESULTS: Twenty-three of 46 children (50%) with persistent
      insomnia had a professional diagnosis of another psychiatric disorder. In the
      remaining 50%, although parents denied any previous psychiatric history, 40%
      displayed psychiatric symptoms as documented by psychometric measures and
      clinical interview. A significant positive correlation was observed between
      depressive BASC score and sleep onset latency and an inverse correlation was
      present with REM sleep latency. CONCLUSION: The vast majority of children
      presenting with persistent insomnia exhibit clinical symptoms of an accompanying
      psychiatric disorder, suggesting that comprehensive psychometric assessments are
      warranted in this population.

PMID- 15165532
TI  - Mouth closing device (chinstrap) reduces mouth leak during nasal CPAP.
AB  - BACKGROUND AND PURPOSE: Mouth leak occasionally complicates continuous positive
      airway pressure (CPAP) therapy, which leads to discomfort. While a chinstrap
      prevents the mouth from opening during sleep, its efficacy in diminishing mouth
      leak has not been studied. PATIENTS AND METHODS: Fifteen patients with mouth leak
      complaining of mouth dryness and nasal obstruction underwent two consecutive
      overnight polysomnographies, one with a chinstrap, in random order. Cephalometry
      with and without a chinstrap was randomly performed on six patients. RESULTS:
      With the chinstrap, both mouth leak and the arousal index decreased
      significantly, from (mean+/-SD) 42.9+/-23.5 to 23.8+/-13.3% of total sleep time
      (TST), and from 33.4+/-18.6 to 23.6+/-9.3/sleep hour, respectively. However,
      snoring time showed a concomitant increase from 6.7+/-14.3 to 24.0+/-13.2% of
      TST. The arousal index was significantly higher during leak periods, and its
      changes correlated positively with changes in mouth leak. Cephalometric measures
      showed a significant decrease in anterior lower facial height. CONCLUSIONS: The
      chinstrap, by closing the mouth during CPAP, reduces mouth leak and therefore the
      arousal index in most patients. Nevertheless, the indices remained unacceptably
      high. The chinstrap may also increase snoring and, in rare cases, can worsen the
      respiratory disturbance index. Consideration of these potential effects is
      important before instituting regular home use of the chinstrap.

PMID- 15165536
TI  - Restless legs syndrome: an historical note.
AB  - The article briefly summarizes the milestones leading to current knowledge and
      the possibility of treating one of the most widespread and perhaps least known
      diseases, restless legs syndrome (RLS). Until the mid-twentieth century, the
      syndrome first described by Willis (1685), was sporadically reported in medical
      literature and in most cases deemed a bizzare condition. It was only with Ekbom's
      detailed clinical description of the syndrome (1944) and the polygraphic
      recordings of Coccagna et al. (1962) that RLS became well-recognised clinical
      entity. Since then, almost all sleep laboratories have devoted much of their
      research to discovering the pathogenetic mechanisms underlying the disease and
      devise increasingly specific treatment. Major advances have been made in recent
      years, but a full understanding of RLS is still a long way off.

PMID- 15165533
TI  - Reverse sleep state misperception.
AB  - A 71-year-old woman with a 3-year history of excessive daytime sleepiness and an
      increased need for sleep did not feel restored upon awakening and had daytime
      fatigue despite a full night's sleep. She was evaluated with polysomnography
      (PSG). She significantly underestimated her sleep latency and awake time after
      sleep onset. The following morning, she stated that she had slept all night, when
      in fact she had extremely poor sleep efficiency and prolonged sleep latency.
      Another PSG and a two-week long actigraphy confirmed her misperception.
      Therefore, she perceived physiologic wakefulness, by PSG and actiraphy criteria,
      as subjective sleep, in direct contrast to 'conventional' sleep state
      misperception, in which patients usually present with a complaint of insomnia but
      have normal sleep quality and duration by PSG criteria. This patient may have a
      previously undescribed variation of sleep state misperception that the authors
      have tentatively named 'reverse' sleep state misperception.

PMID- 15165537
TI  - Subjective and objective criteria in the diagnosis of the restless legs syndrome.

PMID- 15165538
TI  - Epidemiology and clinical findings of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a sensory-motor disorder characterized by
      discomfort of and urge to move the legs, primarily during rest or inactivity,
      partial or total relief with movement, with presence or worsening exclusively in
      the evening. It is a relatively common but frequently unrecognized disorder, with
      a prevalence ranging from 2.5 to 15% of the general population, increasing with
      age and with a female preponderance. The diagnosis is clinical but
      polysomnography is useful to determine its profound impact on sleep (difficulties
      in sleep onset, maintaining sleep during the night, and sleep fragmentation) and
      for the evidence of periodic legs movements during sleep and wake. RLS is
      generally idiopathic, with familial association in 40-60% of the cases, but may
      also be symptomatic of such associated conditions (secondary forms) as peripheral
      neuropathies, uremia, iron deficiency (with or without anemia), diabetes,
      Parkinson's disease and pregnancy. Response to dopaminergic drugs indicates that
      dopamine receptors are implicated, and although much progress has been made in
      diagnosis and treatment in the last decade, more is needed for complete
      elucidation of the etiology and pathophysiology of RLS.

PMID- 15165539
TI  - Genetics in restless legs syndrome.
AB  - Several studies on Restless legs syndrome (RLS) have suggested a substantial
      genetic contribution in the etiology of this sleep disorder. Clinical surveys of
      idiopathic RLS patients have shown that up to 60% report a positive family
      history. Investigations of single families with RLS have suggested an autosomal
      dominant mode of inheritance with variable expressivity, and some families show
      possible anticipation. At present, only one twin study is available, showing a
      high concordance rate (83.3%) between identical twins. Despite several reports
      suggesting a genetic contribution to the etiology of idiopathic RLS, few
      molecular genetic studies have been carried out attempting to identify genes that
      can predispose to this disorder. In particular, genes encoding for the GABA A
      receptor subunits, the gene for the alpha1 subunit of the glycine receptor, and
      genes involved in dopaminergic transmission and metabolism have been analyzed,
      but no significant findings have been reported. Genome-wide studies have been
      conducted to map genes that play a role in vulnerability to RLS. In a single
      French-Canadian family significant linkage was established on chromosome 12q. The
      susceptibility locus on chromosome 12q was not confirmed in two South Tyrolean
      families, or in our two Italian families. However, the efforts toward the
      identification of RLS genes must continue in order to obtain a better
      characterization of the syndrome and to identify new therapeutic strategies.

PMID- 15165540
TI  - Pregnancy as a risk factor for restless legs syndrome.
AB  - Pregnant women have at least two or three times higher risk of experiencing
      restless legs syndrome (RLS) than the general population. These data come from
      few epidemiological studies finding an 11-27% prevalence of RLS during pregnancy.
      Women affected by pre-existing RLS often complain of worsening symptoms during
      pregnancy. This is usually a benign form of RLS, with the highest degree of
      severity in the third trimester and a tendency to disappear around delivery. The
      causes of the association between RLS and pregnancy are unknown. The most debated
      hypotheses are: metabolic alterations, with particular regard to iron and folate
      deficiency; hormonal influences related to the increase of prolactin,
      progesterone and estrogens during late pregnancy; and the changing motor habits
      and psychological state of pregnant women. The importance of folate and iron
      supplementation during pregnancy in preventing RLS is unclear. RLS in pregnant
      women is frequently unrecognized; they are often worried about the symptoms and
      do not receive an adequate explanation by doctors.

PMID- 15165541
TI  - Restless legs syndrome in end-stage renal disease.
AB  - BACKGROUND AND PURPOSE: Patients undergoing dialysis therapy due to end-stage
      renal disease (ESRD) present a high prevalence of sleep disorders, including
      restless legs syndrome (RLS). However, the known data generally have been
      obtained from relatively small patient samples, coming from single or very few
      dialysis units. Moreover, some data were collected prior to the recent
      improvements in dialysis techniques, pharmacological therapies and to the
      establishment of internationally recognised diagnostic criteria for RLS. PATIENTS
      AND METHODS: In order to study the incidence of the different sleep disorders,
      and of RLS in particular, in a large population of dialysis patients, a
      questionnaire was administered to all the patients in dialysis units of the
      'Triveneto' area (Italy) who agreed to participate. The first part of the
      questionnaire included questions about demographic data, general medical history,
      history of renal disease, dialytic treatment and pharmacological therapy. The
      second part, which was self-administered, explored the patient's complaints about
      sleep, the presence of the minimal International Restless Legs Syndrome Study
      Group (IRLSSG) criteria for the diagnosis of RLS, the Epworth Sleepiness Scale
      and questions particularly related to somnolence. Patients whose responses
      indicated a diagnosis of RLS according to the IRLSSG criteria were requested to
      answer the 10 questions of the IRLSSG Severity Scale. The same group of patients
      was compared to those who did not fulfil any of the four minimal criteria for
      RLS. Statistical analysis was performed by using ANOVA and non-parametric tests.
      Whenever possible, data were compared with the database of the Veneto Dialysis
      Register. The first 601 consecutive questionnaires that we were able to analyse
      are presented in this paper. RESULTS: Applying the IRLSSG criteria for the
      diagnosis, the percentage of RLS patients in our sample was 21.5%, with a score
      of 20.5+/-8.7 on the IRLSSG Severity Scale. Comparing patients who are definitely
      affected by RLS (n=127) with unaffected patients (n=280), we found that the two
      groups did not differ as to age, sex, weight, body mass index (BMI), and intake
      of nicotine, alcohol and caffeine. Similarly, the two groups did not differ as to
      the etiology of ESRD, type of dialysis or percentage of previous
      transplantations; however, the period of dialysis dependence was significantly
      lower in the group negative for RLS. The use of drugs did not differ in the two
      groups, except for lower intake of phosphorus binders and antihypertensive drugs
      among RLS patients. No patient was receiving specific treatment for RLS. RLS
      patients reported more fragmented, less restful nightly sleep and more daytime
      somnolence, more often presented symptoms of other sleep disorders and were more
      affected by anxiety or depression. CONCLUSIONS: The high prevalence of RLS and
      other sleep disorders among uremics requires careful investigation of nocturnal
      sleep; although often underdiagnosed, correct identification of these disorders
      can lead to better therapy and improvement of clinical conditions and quality of
      life. Sleep fragmentation and sleep deprivation caused by RLS may contribute to
      the cardiovascular complications and infections, often with bad prognosis in
      dialysis patients.

PMID- 15165542
TI  - Parkinson's disease and RLS: the dopaminergic bridge.
AB  - Dopamine is a neurotransmitter that modulates diverse waking behaviors including
      movement, motivation, cognition, reward, and feeding. Interest in dopamine's
      additional contributions to normal and pathologic sleep-wake states has
      experienced a recent rebirth originating from two clinical disorders: Parkinson's
      disease and Restless Legs Syndrome. The former, the prototypical disorder of
      brain dopamine cell loss, is accompanied by marked sleep disruption and
      impairments in daytime alertness. The latter is exquisitively responsive to
      pharmacologic agents that act upon dopamine receptors. The potential
      neurobiological substrates underlying these observations are reviewed here.
      Converging lines of evidence suggest that mesocorticolimbic dopamine circuits are
      involved in promoting wakefulness, while a less studied diencephalospinal
      dopamine system might underly the sensorimotor dysfunction of Restless Legs
      Syndrome.

PMID- 15165543
TI  - Human feelings: why are some more aware than others?
AB  - A recent article reports that human perception of heartbeat timing is mediated by
      right (non-dominant) anterior insular cortex, and that the activity and the size
      of this region is directly correlated with individuals' subjective awareness of
      inner body feelings and emotionality. These results support the somatic-marker
      hypothesis of consciousness (a modern successor to the James-Lange theory of
      emotion) and the neuroanatomical concept that human awareness is based on a
      phylogenetically distinct interoceptive pathway.

PMID- 15165544
TI  - Awareness in memory: being explicit about the role of sleep.
AB  - Sleep is crucial to the 'off-line' consolidation of procedural memory. A recent
      study by Robertson et al. shows that this might hold true only if the task is
      trained explicitly, that is, with the subject being aware of the task structure.
      These new data add to emerging evidence that sleep-related memory consolidation
      involves an interaction between different memory systems.

PMID- 15165545
TI  - Processing local transitions versus long-distance syntactic hierarchies.
AB  - A recent study by Fitch and Hauser reported that finite-state grammars can be
      learned by non-human primates, whereas phrase-structure grammars cannot. Humans,
      by contrast, learn both grammars easily. This species difference is taken as the
      critical juncture in the evolution of the human language faculty. Given the far
      reaching relevance of this conclusion, the question arises as to whether the
      distinction between these two types of grammars finds its reflection in different
      neural systems within the human brain.

PMID- 15165546
TI  - FOXP2 and the language working-memory system.

PMID- 15165548
TI  - Bilingual word perception and production: two sides of the same coin?

PMID- 15165550
TI  - Understanding children's and adults' limitations in mental state reasoning.
AB  - Young children exhibit several deficits in reasoning about their own and other
      people's mental states. We propose that these deficits, along with more subtle
      limitations in adults' social-cognitive reasoning, are all manifestations of the
      same cognitive bias. This is the 'curse of knowledge' - a tendency to be biased
      by one's own knowledge when attempting to appreciate a more naive or uninformed
      perspective. We suggest the developmental differences in mental state reasoning
      exist because the strength of this bias diminishes with age, not because of a
      conceptual change in how young children understand mental states. By pointing out
      the common denominator in children's and adults' limitations in mental state
      reasoning we hope to provide a unified framework for understanding the nature and
      development of social cognition.

PMID- 15165551
TI  - Neuronal representations of cognitive state: reward or attention?
AB  - The effects of spatial or featural attention on the activity of neurons have been
      studied in many experiments that have used a variety of neurophysiological
      approaches. Other experiments have examined how expectations about reward are
      represented in neuronal activity in various brain regions. Although attention and
      reward are distinct concepts, I argue here that many neurophysiological
      experiments on attention and reward do not permit a clean dissociation between
      the two. This problem arises in part because reward contingencies are the only
      parameter manipulated in any of these experiments. I describe how attention and
      reward expectations have been confounded, giving rise to uncertainty about how
      signals related to attention and reward are distributed in the brain.

PMID- 15165552
TI  - An action perspective on motor development.
AB  - Motor development has all too often been considered as a set of milestones with
      little significance for the psychology of the child. Nothing could be more wrong.
      From an action perspective, motor development is at the heart of development and
      reflects all its different aspects, including perception, planning and
      motivation. Recent converging evidence demonstrates that, from birth onwards,
      children are agents who act on the world. Even in the newborn child, their
      movements are never just reflexes. On the contrary, they are purposeful goal
      directed actions that foresee events in the world. Thus, motor development is not
      just a question of gaining control over muscles; equally important are questions
      such as why a particular movement is made, how the movements are planned, and how
      they anticipate what is going to happen next.

PMID- 15165553
TI  - TMS in cognitive plasticity and the potential for rehabilitation.
AB  - Cognitive neuroscientists use transcranial magnetic stimulation (TMS) in several
      ways, from aiming to increase understanding of brain-behavior relationships to
      transiently improving performance, both in normals and in patients with
      neurological and neuropsychological deficits. Different types of TMS (single
      pulse, paired-pulse, repetitive) are able to interfere with higher brain
      functions that require the cooperation of different brain areas and complex
      neuronal networks. Currently, behavioral TMS effects on the brain are usually
      short-lived and their underlying mechanisms not yet wholly understood. However,
      the aim of using TMS to develop rehabilitative strategies for motor, perceptive
      and cognitive functions represents an intriguing challenge.

PMID- 15165554
TI  - Mechanical reasoning by mental simulation.
AB  - Recent studies have provided evidence for mental simulation as a strategy in
      mechanical reasoning. This type of reasoning can be dissociated from reasoning
      based on descriptive knowledge in that it depends on different abilities and
      memory stores, is expressed more easily in gesture than in language, exhibits
      analog properties, and can result in correct inferences in situations where
      people do not have correct descriptive knowledge. Although it is frequently
      accompanied by imagery, mental simulation is not a process of inspecting a
      holistic visual image in the 'mind's eye'. Mental simulations are constructed
      piecemeal, include representations of non-visible properties and can be used in
      conjunction with non-imagery processes, such as task decomposition and rule-based
      reasoning.

PMID- 15165555
TI  - Signals from the underground: bacterial volatiles promote growth in Arabidopsis.

PMID- 15165556
TI  - Valencene synthase--a biochemical magician and harbinger of transgenic aromas.

PMID- 15165557
TI  - Evergreen trees do not maximize instantaneous photosynthesis.

PMID- 15165558
TI  - Evolution of endophyte-plant symbioses.

PMID- 15165559
TI  - The new genes of rice: a closer look.

PMID- 15165560
TI  - Achieving successful deployment of Bt rice.

PMID- 15165561
TI  - Genetics and genomics of chloroplast biogenesis: maize as a model system.

PMID- 15165562
TI  - Auxin signaling and regulated protein degradation.

PMID- 15165563
TI  - Signalling for developmental plasticity.

PMID- 15165564
TI  - The molecular chaperone Hsc70 from a eurythermal marine goby exhibits temperature
      insensitivity during luciferase refolding assays.
AB  - The role and function of molecular chaperones has been widely studied in model
      systems (e.g. yeast, Escherichia coli and cultured mammalian cells), however,
      comparatively little is known about the function of molecular chaperones in
      eurythermal ectotherms. To investigate the thermal sensitivity of molecular
      chaperone function in non-model ectotherms, we examined the in vitro activity of
      Hsc70, a constitutively expressed member of the 70-kDa heat-shock protein gene
      family, purified from white muscle of the eurythermal marine goby Gillichthys
      mirabilis. The activity of G. mirabilis Hsc70 was assessed with an in vitro
      refolding assay where the percent refolding of thermally denatured luciferase was
      monitored using a luminometer. Assays were conducted from 10-40 degrees C, a
      range of temperatures that is ecologically relevant for this estuarine species.
      The results showed that isolated Hsc70 displayed chaperone characteristics in
      vitro, and was relatively thermally insensitive across the range of experimental
      temperatures. In addition, the thermal stability of the luciferase refolding
      capacity of Hsc70 was relatively stable, with refolding activity occurring as
      high as 50 degrees C. Overall, Hsc70 from G. mirabilis displayed thermal
      properties in vitro that suggest that the molecular chaperone is capable of
      binding and chaperoning proteins at temperatures that the goby encounters in
      nature.

PMID- 15165565
TI  - Changes in some nitrogenous compounds in the blood and tissues of freshwater
      pikeperch (Sander lucioperca) during salinity acclimation.
AB  - The effect of ambient salinity changes (0.9, 6 and 12 psu) on the levels of
      dissolved ammonia (DA), ninhydrin positive substances (NPS), trimethylamine (TMA)
      and trimethylamine oxide (TMAO) in the blood and tissue of medium-acclimated
      Sander lucioperca L. (also Stizostedion lucioperca) were investigated. In
      freshwater, blood and tissue total free amino acid levels (measured as NPS) were
      3.62 mM and 60.61 mM, respectively. The NPS content increased significantly
      (P<0.05) in the tissue and blood on acclimation to 6 and 12 psu salinities. The
      mass-specific tissue TMAO concentration of pikeperch acclimated to normal
      freshwater was 0.413+/-0.084 micromol TMAO g(-1). Results reveal that TMAO levels
      are positively influenced by the external salinity medium where significant
      differences in mean levels occurred between the groups (P<0.05). The calculated
      p[NH(3)] and [NH(4)(+)] gradients reveal that the [NH(3)] gradient was
      consistently low (cf. the [NH(4)(+)] gradient). The gradient of p[NH(3)]
      decreased with the medium increased salinities. The results suggest that
      freshwater pikeperch may be able to resist salinity changes by manipulation of
      nitrogen metabolism. Free amino acids and TMAO are involved in mediating response
      to salinity exposure in freshwater pikeperch.

PMID- 15165566
TI  - Peripheral leptin administration alters hormone and metabolite levels in the
      young pig.
AB  - The present study was conducted to determine if peripheral leptin administration
      can alter GH secretion or feed intake in young pigs. Six, 6 kg female pigs were
      fasted overnight and randomly chosen to receive porcine recombinant leptin or
      saline injections in a crossover design. Three leptin dosages were tested over a
      10 day period, 100, 200 or 500 microg/kg body mass (L100, L200 or L500). Leptin
      was administered in 0.2% bovine serum albumin as a bolus injection into the
      carotid artery. Blood samples were obtained from the jugular vein over a 24 h
      period. Leptin delayed feeding in pigs treated with L200 and L500 (P<0.05), while
      reducing overall intake in pigs treated with L100 (P<0.05). L200 or L500
      depressed blood glucose (P<0.05). Plasma insulin levels were elevated by feeding
      in control animals, while insulin levels were depressed in pigs treated with L200
      or L500 (P<0.05). L200 elevated plasma growth hormone (P<0.05) with three peaks
      apparent at 5, 8, and 13 h post injection. The ability for a single injection of
      leptin to produce significant changes in hormone and metabolite levels suggests
      that this peptide has a role in regulation of peripheral metabolism.

PMID- 15165567
TI  - Plasma clearance and tissue distribution of radiolabeled leptin in the chicken.
AB  - Leptin is an adipose and liver tissue-derived secreted protein in chickens that
      has been implicated in the regulation of food intake and whole-body energy
      balance. In this study, the metabolic clearance and tissue uptake of leptin were
      examined in the chicken (Gallus gallus). Four-week-old broiler males were infused
      with (125)I-labeled mouse leptin. Chromatography of radiolabeled leptin in plasma
      produced two peaks, one at 16 kDa (free leptin) and a free iodine peak. No leptin
      binding protein in blood was detected. Leptin was cleared with a half-life
      estimate of 23 min. In order to investigate the tissue distribution and uptake of
      radiolabeled leptin, multiple tissues were removed from infused birds at 15 and
      240 min post-infusion, and trichloroacetic acid (TCA)-precipitable radioactivity
      was determined. The amounts of radioactivity at 15 min post-infusion in the
      tissues in rank order were: kidney, testis, lung, spleen, heart, liver, small and
      large intestine, gizzard, pancreas, bursa, leg and breast muscle, adrenals, and
      brain. A slightly different pattern of distribution was observed at 240 min post
      infusion. We conclude from these studies that unlike mammals, no circulating
      leptin binding protein is present in chickens. Leptin is metabolized and cleared
      very rapidly from blood by the kidney.

PMID- 15165568
TI  - Embryogenesis and oxygen consumption in benthic egg clutches of a tropical
      clownfish, Amphiprion melanopus (Pomacentridae).
AB  - Variation in size at hatching is common in demersal spawning organisms,
      suggesting that processes during embryonic development may be critical in
      determining growth and development. To examine critical periods during embryonic
      development in the demersal spawning reef fish Amphiprion melanopus, the rate of
      oxygen consumption within an egg clutch was compared to morphological changes in
      the embryos. Oxygen consumption was least on day 1 of development where organ
      differentiation had not begun (mean 1.73+/-0.34x10(-5) micromol O(2) egg(-1) s(
      1)). Tail movement throughout the perivitelline fluid began on day 3 and is
      likely to assist in moving oxygen around the embryo, complementing diffusive
      transport. The appearance of haemoglobin in the blood corresponded to a peak in
      oxygen consumption on day 4, where the highest mean rate of oxygen consumption
      was recorded (6.73+/-0.82x10(-5) micromol O(2) egg(-1) s(-1)). This could be a
      critical period in development whereby risk of mortality is increased through
      increased embryo requirements at developmental thresholds.

PMID- 15165569
TI  - Host physiological changes due to parasitism of a braconid wasp, Cotesia
      plutellae, on diamondback moth, Plutella xylostella.
AB  - Braconid wasps, Cotesia plutellae (Kurdjumov), were collected from parasitized
      host larvae of diamondback moth, Plutella xylostella (L.) in Korea. Virus
      particles were found in the oviduct lumen of C. plutellae females. Multiple
      nucleocapsids with approximately 30-nm diameter and variable length (30-80 nm)
      were surrounded with a single unit membrane envelope. The parasitization of C.
      plutellae completely inhibited pupal metamorphosis. The parasitized larvae showed
      significant decrease in feeding activity and total hemolymph proteins, especially
      as larval storage proteins. They also showed a significant decrease in immune
      capacity as evidenced by reduced ability to form hemocyte nodules and reduced
      phenoloxidase and lysozyme activity. Here, we show that C. plutellae has an
      endosymbiotic virus like other reported species in Microgastrinae, and suggest
      that it causes host developmental arrest and immune-depression at parasitization.

PMID- 15165570
TI  - Haematological parameters in Umbrina cirrosa (Teleostei, Sciaenidae): a
      comparison between diploid and triploid specimens.
AB  - Haematological features were compared between diploid and triploid specimens of
      the ray-finned fish Umbrina cirrosa. No significant differences between diploids
      and triploids were reported in haematocrit and total haemoglobin concentration,
      but erythrocytes and thrombocytes were significantly greater in size in
      triploids. Glycaemia was significantly lower in diploids, whereas triploid
      erythrocytes were more resistant to osmotic stress. In triploids, a greater
      fraction of leukocytes was positive for alkaline phosphatase activity, when
      stimulated with Bacillus clausii spores, otherwise no significant increase of
      oxygen consumption was observed in triploid leukocytes after stimulation, based
      on assays for superoxide anions. Triploids were characterized by a lower
      concentration of circulating blood cells with a lower surface/volume ratio when
      compared with diploids. These features may lead to a general disadvantage of
      triploids in withstanding stress conditions: a situation that needs to be taken
      into account in aquaculture practice.

PMID- 15165571
TI  - Trypsinogen expression during the development of the exocrine pancreas in winter
      flounder (Pleuronectes americanus).
AB  - Histological, biochemical and molecular techniques were used to describe the
      functional development of the pancreas in winter flounder (Pleuronectes
      americanus) with specific reference to the expression of three trypsinogen genes.
      The pancreas was identified shortly following hatch, appearing as a compact
      structure situated dorsal and slightly posterior to the liver. As the larval fish
      approached metamorphosis, the pancreas became diffuse, spreading throughout the
      mesentery surrounding the stomach, the upper intestine and the pyloric caecae.
      Trypsin 2 expression was detected from 5 days post-hatch (dph). Two other related
      trypsinogen genes isolated from the pyloric caecae (Trypsin 1) and the intestine
      (Trypsin 3) showed contrasting results. Trypsin 1 showed very low levels of
      expression and only in late larval stages and metamorphosis. Trypsin 3 showed
      expression only after 20 dph. In order to determine tissue-specific expression of
      the three trypsinogen genes, the RNA from seven gastrointestinal-associated
      tissues was examined. Trypsin 1 and Trypsin 2 expression was most notably
      associated with the pyloric caecae, cardiac stomach, pyloric stomach and the
      rectum, although some variation in expression level between tissues was observed.
      Trypsin 3 expression had a narrower tissue distribution and was only associated
      with the pyloric caecae and the rectum. The tissue expression patterns observed
      here are likely due in part to the diffuse nature of the pancreas. Trypsin-like
      activity was evident from hatch and continued at significant levels through to at
      least 25 dph.

PMID- 15165572
TI  - Estimation of neuronal population activity changes in rat cerebellum using one
      electrode.
AB  - Activity of neuronal populations is usually measured with multielectrode systems.
      In this paper a procedure is described for estimating population activity changes
      in rat cerebellar cortex, using one microelectrode. Signals consisted of simple,
      complex spikes and interspike recorded background activity (RBA). After their
      separation, simple spikes were averaged, forming a simple spike template (SST).
      The remaining RBA was simulated (SBA), by superimposing SST waveforms with random
      time delays and intensities. A series of SBA was formed, differing in the
      superposition frequency (f(sup)) of individual SST. Mean amplitude spectra
      (Amp(SBA)) were calculated and Amp(SBA)=f(f(sup)) treated as a calibration line
      for estimating activity level of the surrounding neuronal population. Since the
      uniform probability distribution of SST intensities proved inadequate, we derived
      a new one, based on the power function for spike intensity vs. electrode distance
      attenuation. A family of new lines emerged, depending on the model parameters.
      Since all were linear in the log-log plots, with slopes not varying
      significantly, we proposed a method for estimating population activity changes in
      different experimental conditions, using two measured values of Amp(RBA).
      Relative nature of the results makes this method suitable for comparative
      studies.

PMID- 15165573
TI  - Serotonergic regulation of the central heart auricles of Sepia officinalis L.
      (Mollusca, Cephalopoda).
AB  - In pharmacological bioassays on isolated isotonically suspended auricles of Sepia
      officinalis, the regulatory action of the neurotransmitter serotonin (5
      hydroxytryptamine, 5-HT) on these autonomous contractile compartments was
      demonstrated. 5-HT induced concentration-dependent positive effects on frequency
      and tone, whereas the concentrations/response curve for the amplitude showed a
      biphasic course. All applied antagonists inhibited mainly the effect of 5-HT on
      frequency and amplitude. The chronotropic effects of 5-HT were blocked mainly by
      the 5-HT(1,2) antagonist methiothepin (pA(2)=8.01), the 5-HT(1a) antagonist NAN
      190 (pA(2)-) and in lesser extent by the 5-HT(1,2) antagonist mianserin
      (pA(2)=6.81). In the presence of each antagonist applied the 5-HT action on
      amplitude was transformed into a positive inotropic effect with the maximum under
      influence of NAN-190 and the 5-HT(2,1c)-antagonist ketanserin. The auricular tone
      was also influenced by the antagonists and in combination with methiothepin it
      turned into strong negative tonotropic effect. In addition to the pharmacological
      bioassays, the presence of 5-HT in nerve endings within the auricle wall was
      demonstrated by immunohistochemical and fluorescence microscopic findings.
      Altogether the findings presented here confirm that 5-HT evokes excitatory
      effects on the autonomous contractile auricle of S. officinalis and acts
      obviously over different receptors, whereby a 5-HT(1)- and a 5-HT(2)-like seem to
      be involved.

PMID- 15165574
TI  - Expression of prolactin receptor mRNA in the abdominal gland of the newt Cynops
      ensicauda.
AB  - To further the understanding that the structural development of the Cynops
      ensicauda abdominal gland and the synthesis of the pheromone silefrin in the
      gland are under the control of prolactin and androgen, we sought to demonstrate
      the presence of prolactin receptor (PRLR) mRNA in the gland. Firstly, PRLR cDNA
      was isolated from an abdominal gland cDNA library. A cDNA consisting of a 415-bp
      5'-untranslated region, 1878-bp open reading frame and 175-bp 3'-untranslated
      region was obtained. The deduced amino acid sequence consisted of 626 amino acids
      with signal peptide and single transmembrane domain. By Northern blot analysis
      using partial C. ensicauda PRLR cDNA, two transcripts, of 3 and 10 kb, were
      detected for PRLR in the brain, liver, kidney, abdominal gland, oviduct and skin.
      RT-PCR coupled with Southern blot analysis showed that the PRLR gene was
      transcribed broadly in newt organs and revealed that PRLR mRNA levels in the
      abdominal gland were much higher in sexually developed newts than in the sexually
      undeveloped ones. By in situ hybridization, specific signals were detected in the
      epithelial cells of the abdominal gland of sexually developed newts, but much
      less in those of the sexually undeveloped ones.

PMID- 15165575
TI  - Post-hatching dynamics of plasma biochemistry in free-living European starlings
      (Sturnus vulgaris).
AB  - This is the first study of plasma biochemical parameters in free-living altricial
      birds during an entire developmental period in a nest, represented by European
      starling (Sturnus vulgaris). Dynamics of postnatal changes from hatching until
      close to fledging (days 1 to 15) were registered. Parameters of protein
      metabolism represented by total proteins, albumin and globulin concentrations
      increased continuously during the observed developmental period. There were two
      peaks in uric acid concentration on days 5 and 11. To the contrary, the
      creatinine content did not change throughout the observed period and increased
      only on day 15. Creatine kinase activity gradually increased until day 11 and
      then fell before fledging. Parameters of lipid metabolism (concentration of total
      lipids, triacylglycerols and nonesterified fatty acids) in plasma increased
      gradually reaching a plateau between days 8 and 11 and then declined on day 15.
      The cholesterol concentration pattern was similar to maximum value on day 11,
      then consecutively decreased. Concentration of glucose increased until day 8 and
      remained unchanged until fledging. Whereas calcium reached the highest
      concentration during days 8 and 11, phosphorus peaked earlier on day 5. The
      activity of alkaline phosphatase was similar to the pattern found in calcium
      concentration. Presented data showed an increase in both protein and lipid
      metabolism during the phase of rapid growth. A remarkable decrease in parameters
      of lipid metabolism before fledging may reflect increased physical activity and
      changes in nutrition.

PMID- 15165576
TI  - Regulation of breathing and body temperature of a burrowing rodent during hypoxic
      hypercapnia.
AB  - Burrowing mammals usually have low respiratory sensitivity to hypoxia and
      hypercapnia. However, the interaction between ventilation (V), metabolism and
      body temperature (Tb) during hypoxic-hypercapnia has never been addressed. We
      tested the hypothesis that Clyomys bishopi, a burrowing rodent of the Brazilian
      cerrado, shows a small ventilatory response to hypoxic-hypercapnia, accompanied
      by a marked drop in Tb and metabolism. V, Tb and O(2) consumption (V?O(2)) of C.
      bishopi were measured during exposure to air, hypoxia (10% and 7% O(2)),
      hypercapnia (3% and 5% CO(2)) and hypoxic-hypercapnia (10% O(2)+ 3% CO(2)).
      Hypoxia of 7% but not 10%, caused a significant increase in V, and a significant
      drop in Tb. Both hypoxic levels decreased V?O(2) and 7% O(2) significantly
      increased V/V?O(2). Hypercapnia of 5%, but not 3%, elicited a significant
      increase in V, although no significant change in Tb, V?O(2) or V/V?O(2) was
      detected. A combination of 10% O(2) and 3% CO(2) had minor effects on V and Tb,
      while V?O(2) decreased and V/V?O(2) tended to increase. We conclude that C.
      bishopi has a low sensitivity not only to hypoxia and hypercapnia, but also to
      hypoxic-hypercapnia, manifested by a biphasic ventilatory response, a drop in
      metabolism and a tendency to increase V/V?O(2). The effect of hypoxic-hypercapnia
      was the summation of the hypoxia and hypercapnia effects, with respiratory
      responses tending to have hypercapnic patterns while metabolic responses, hypoxic
      patterns.

PMID- 15165577
TI  - Elevated free tyrosine in rhinoceros erythrocytes.
AB  - Red blood cells of African black rhinoceroses (Diceros bicornis) are highly
      sensitive to oxidant-induced hemolysis and they possess a number of enzymatic and
      biochemical features that differ radically from other mammals. Here we show
      concentrations of free tyrosine in rhinoceros red blood cells which can approach
      levels as high as 1 mM, 50-fold higher than in human red blood cells. Elevated
      levels of tyrosine are also observed in red blood cells of other members of the
      order Perissodactyla such as the horse and zebra. Captive black rhinoceroses have
      significantly lower levels of red blood cell tyrosine than black rhinoceroses in
      the wild. Tyrosine transport studies indicate that black rhinoceros red blood
      cells have lost the ability to transport tyrosine as efficiently as human red
      blood cells.

PMID- 15165578
TI  - Oxygen and carbon dioxide sensitivity of ventilation in amphibious crabs,
      Cardisoma guanhumi, breathing air and water.
AB  - Amphibious crabs, Cardisoma guanhumi, were acclimated to breathing either air or
      water and exposed to altered levels of oxygen and/or carbon dioxide in the
      medium. Hypercapnia (22, 36 and 73 torr CO(2)) stimulated a significant
      hypercapnic ventilatory response (HCVR) in both groups of crabs, with a much
      greater effect on scaphognathite frequency (Deltaf(SC)=+700%) in air-breathing
      crabs than water-breathing crabs (Deltaf(SC)=+100%). In contrast, hyperoxia
      induced significant hypoventilation in both sets of crabs. However, simultaneous
      hyperoxia and hypercapnia triggered a greater than 10-fold increase in f(SC) in
      air-breathing crabs but no change in water-breathing crabs. For water-breathing
      crabs hypoxia simultaneous with hypercapnia triggered the same response as
      hypoxia alone-bradycardia (-50%), and a significant increase in f(SC) at moderate
      exposures but not at the more extreme levels. The response of air-breathing crabs
      to hypoxia concurrent with hypercapnia was proportionally closer to the response
      to hypercapnia alone than to hypoxia. Thus, C. guanhumi were more sensitive to
      ambient CO(2) than O(2) when breathing air, characteristic of fully terrestrial
      species, and more sensitive to ambient O(2) when breathing water, characteristic
      of fully aquatic species. C. guanhumi possesses both an O(2)- and a CO(2)-based
      ventilatory drive whether breathing air or water, but the relative importance
      switches when the respiratory medium is altered.

PMID- 15165579
TI  - Diabetic neuropathy: the painful foot.
AB  - Diabetic neuropathy typically present as a mixture of sensory, motor and
      autonomic involvement. The development and severity of the neuropathy varies.
      This article briefly reviews the types of diabetic neuropathy and their
      relationship to pain and discusses the proposed etiologies.

PMID- 15165580
TI  - The role of surgical decompression for diabetic neuropathy.
AB  - Surgical decompression of peripheral nerves for the treatment of diabetic
      peripheral neuropathy has been studied and previously reported. These studies
      reported decreased pain and some studies showed improved sensory function. The
      role that this surgery can play remains controversial.

PMID- 15165581
TI  - Peripheral nerve entrapments.
AB  - Peripheral nerve entrapment is a rare, but important, cause of foot and ankle
      pain that often is underdiagnosed and mistreated. A peripheral nerve may become
      entrapped anywhere along its course, but certain anatomic locations are
      characteristic. Clinically,nerve entrapment is divided into three stages: in
      stage I patients feel rest pain and intermittent paresthesias which are worse at
      night; in stage II, continued nerve compression leads to paresthesias, numbness,
      and, occasionally, muscle weakness that does not disappear during the day, and in
      stage III, patients describe constant pain, muscle atrophy, and permanent sensory
      loss. Diagnostic confusion abounds because of the multiple etiologies of
      peripheral nerve entrapments and their complex physical and temporal relation. A
      thorough understanding of the causes of peripheral nerve entrapments, the
      anatomic course and variation of the peripheral nerves, the diagnostic
      modalities, and the treatment options can simplify this complex problem.

PMID- 15165582
TI  - Posterior tibial nerve--primary.
AB  - Tarsal tunnel is an uncommon disorder of the foot that presents as a burning or
      tingling pain that is located diffusely on the plantar aspect of the foot. Many
      investigators have considered tarsal tunnel syndrome to be analogous to carpal
      tunnel syndrome. As more becomes known about tarsal tunnel syndrome, it is
      evident that this is not purely an entrapment neuropathy. It differs from carpal
      tunnel syndrome in anatomy, etiology, clinical presentation, and response to
      nonoperative and operative treatment.

PMID- 15165583
TI  - Interdigital neuromas: current state of the art--surgical.
AB  - Several reports demonstrated that the interdigital neuroma is a form of
      entrapment neuropathy. Nonoperative measures may provide satisfactory results to
      some patients, but surgical treatment seems to provide more predictable results
      and lasting pain relief. Neurectomy remains the most commonly used procedure for
      the treatment of interdigital neuritis through a plantar or a dorsal approach.
      Outcome results after neurectomy note a failure rate of 2% to 35%.

PMID- 15165584
TI  - Endoscopic decompression of the intermetatarsal nerve for Morton's neuroma.
AB  - Endoscopic decompression of the intermetatarsal nerve offers many advantages over
      other current techniques. Preliminary results in the first 40 patients have been
      excellent with no hematomas or infections; only three patients returned to the
      operating room for neurectomy.

PMID- 15165585
TI  - Revision peripheral nerve surgery.
AB  - The treatment of chronic neuropathic pain with revision surgical procedures can
      be beneficial. A thorough evaluation can help to guide treatment to optimize
      outcome. With an increasing understanding of the pain-generating mechanisms and
      the appropriate application of surgical interventions, quality of life and
      function continues to be improved in patients who have otherwise significant
      disability.

PMID- 15165586
TI  - The uses of tendon transfers to correct paralytic deformity of the foot and
      ankle.
AB  - Tendon transfers for paralytic foot and ankle deformities can be rewarding in
      well-selected patients. The goal should be to achieve a stable plantigrade foot
      which optimally will not require a brace. This is possible if there is adequate
      preoperative tendon strength, adherence to the basic principles of tendon
      transfer during surgery, and intensive retraining of the muscle in the recovery
      phase. The optimal method of tendon fixation remains unclear.

PMID- 15165587
TI  - Clinical usefulness of botulinum toxin in the lower extremity.
AB  - As the literature that pertains to botulinum toxin expands, the scope of
      treatment options broadens. Although initial uses of botulinum toxin focused
      around the head and neck, there are many uses for the toxin in the area of the
      foot and ankle; more possibilities are under investigation every day. We review
      the uses and techniques for botulinum toxin in the foot and ankle and present
      results of botulinum toxin treatment in 10 idiopathic toe walkers.

PMID- 15165588
TI  - Regional anesthesia techniques for the lower extremity.
AB  - This article focuses on regional anesthesia for orthopedic procedures of the
      lower extremity.

PMID- 15165589
TI  - The medical management of chronic pain.
AB  - Pain is defined by the International Association for Study of Pain as "an
      unpleasant sensory and emotional experience associated with actual or potential
      tissue damage or described in terms of such damage." This article reviews the
      medical management of chronic pain.

PMID- 15165590
TI  - Interventional modalities in the treatment of complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) applies to a variety of conditions in which
      symptoms such as allodynia and hyperalgesia predominate along with hyperpathia
      and vasomotor/sudomotor disturbances. The incidence of CRPS in the chronic pain
      population varies and is difficult to determine, though it appears to affect
      women more than men. Treatment is multidisciplinary, and recovery of function and
      the reduction of pain are the main goals of treatment;this article addresses some
      of the interventional modalities that are used.

PMID- 15165593
TI  - The application of independent component analysis to the multi-channel surface
      electromyographic signals for separation of motor unit action potential trains:
      part II-modelling interpretation.
AB  - The purpose of this article was to investigate whether or not FastICA can
      separate identical motor unit action potential trains (MUAPTs) of the 8-channel
      surface electromyographic (sEMG) signals constructed by an sEMG model into the
      independent components. Firstly, we have examined how much the increase of motor
      units (MUs) in the simulated sEMG signals influenced the performance on the
      separation of MUAPTs by kurtosis. The decreased trend of mean kurtosis on both
      sEMG signals and their independent components were observed as MUs were
      increased. These data suggested that the separation performance decayed when MUs
      were increased. Secondary, the differences between the independent components and
      the principal components have been also applied to the simulated sEMG signals
      with or without time delay between the sEMG channels. FastICA could successfully
      separate identical MUAPTs with no time delay but principal component analysis
      (PCA) could not do so. Against it, both FastICA and PCA could not separate MUAPTs
      with some time delay. In conclusion, our results suggested that FastICA could
      separate identical MUAPTs with no time delay into the independent components by
      FastICA, which might offer a new technique for the separation of interfered MUAP
      waveforms based on statistical properties of sEMG signal distributions.

PMID- 15165592
TI  - The application of independent component analysis to the multi-channel surface
      electromyographic signals for separation of motor unit action potential trains:
      part I-measuring techniques.
AB  - The purpose of this study is to examine whether or not the application of
      independent component analysis (ICA) is useful for separation of motor unit
      action potential trains (MUAPTs) from the multi-channel surface EMG (sEMG)
      signals. In this study, the eight-channel sEMG signals were recorded from
      tibialis anterior muscles during isometric dorsi-flexions at 5%, 10%, 15% and 20%
      maximal voluntary contraction. Recording MUAP waveforms with little time delay
      mounted between the channels were obtained by vertical sEMG channel arrangements
      to muscle fibers. The independent components estimated by FastICA were compared
      with the sEMG signals and the principal components calculated by principal
      component analysis (PCA). From our results, it was shown that FastICA could
      separate groups of similar MUAP waveforms of the sEMG signals separated into each
      independent component while PCA could not sufficiently separate the groups into
      the principal components. A greater reduction of interferences between different
      MUAP waveforms was demonstrated by the use of FastICA. Therefore, it is suggested
      that FastICA could provide much better discrimination of the properties of MUAPTs
      for sEMG signal decomposition, i.e. waveforms, discharge intervals, etc., than
      not only PCA but also the original sEMG signals.

PMID- 15165594
TI  - Precision of measurements of physical workload during standardised manual
      handling. Part I: surface electromyography of m. trapezius, m. infraspinatus and
      the forearm extensors.
AB  - Though surface electromyography (EMG) has been widely used in studies of
      occupational exposure, its precision in terms of the variance between-days and
      between-subjects has seldom been evaluated. This study aimed at such an
      evaluation. Six women performed three different work tasks: 'materials picking',
      'light assembly', and 'heavy assembly', repeated on 3 different days. EMG was
      recorded from m. trapezius, m. infraspinatus and the forearm extensors.
      Normalisation was made to a maximal (MVE), and a submaximal (RVE), reference
      contraction. Variance components between days (within subjects) and between
      subjects were derived for the 10th, 50th and 90th percentiles, as well as for
      muscular rest parameters. For the task 'heavy assembly', the coefficient of
      variation between days (CV(BD)) was 8% for m. trapezius (right side, 50th
      percentile, MVE normalised values). Larger variabilities were found for m.
      infraspinatus (CV(BD) 15%), and the forearm extensors (CV(BD) 33%). Between
      subjects variability (CV(BS)) was greater, 16% for m. trapezius and 57% for m.
      infraspinatus, 29% for the forearm extensors. RVE normalisation resulted in
      larger CV(BD), while reducing CV(BS). The between-days and between-subjects
      variability may be used to optimise sampling strategy, and to assess the bias in
      epidemiological studies. The bias caused by measurement procedures per se is
      acceptable.

PMID- 15165595
TI  - The effect of the amplitude of motor action on anticipatory postural adjustments.
AB  - The purpose of this study was to determine whether changes in the amplitude of a
      motor action triggering the same perturbation affect anticipatory postural
      adjustments (APAs). Healthy subjects performed releases of the same load with
      shoulder abduction movements of different amplitudes. Changes in the electrical
      activity of trunk and leg muscles, as well as displacements of the center of
      pressure were recorded. Generally, there were no differences in anticipatory
      activity of muscles and displacements of the center of pressure between series of
      load releases induced by motor actions of different amplitudes. We suggest that
      the CNS arranges APAs based on the magnitude of the perturbation if the same
      muscle groups generate motor actions of different amplitudes.

PMID- 15165596
TI  - Spatio-temporal evaluation of neck muscle activation during postural
      perturbations in healthy subjects.
AB  - The purpose of this study was to examine the spatio-temporal activation of the
      sternocleidomastoid (SCM) and cervical extensor (CE) muscles with respect to the
      deltoid muscle onset during rapid voluntary upper limb movement in healthy
      volunteers. The repeatability and reliability of the spatio-temporal aspects of
      the myoelectric signals were also examined. Ten subjects performed bilateral and
      unilateral rapid upper limb flexion, abduction and extension in response to a
      visual stimulus. EMG onsets and normalised root mean square (nRMS) values were
      calculated for the SCM and CE muscles. Subjects attended three testing sessions
      over non-consecutive days allowing the repeatability and reliability of these
      measures to be assessed. The SCM and CE muscles demonstrated feed-forward
      activation (activation within 50 ms of deltoid onset) during rapid arm movements
      in all directions. The sequence and magnitude of neck muscle activation displayed
      directional specificity, however, the neck flexor and extensor muscles displayed
      co-activation during all perturbations. EMG onsets demonstrated high
      repeatability in terms of repeated measure precision (nSEM in the range 1.9
      5.7%). This was less evident for the repeatability of nRMS values. The results of
      this study provide a greater understanding of cervical neuromotor control
      strategies. During bilateral and unilateral upper limb perturbations, the SCM and
      CE muscles demonstrate feed-forward co-activation. It seems apparent that feed
      forward activation of neck muscles is a mechanism necessary to achieve stability
      for the visual and vestibular systems, whilst ensuring stabilisation and
      protection of the cervical spine.

PMID- 15165597
TI  - Knee joint laxity affects muscle activation patterns in the healthy knee.
AB  - This study investigated the effects of anterior knee joint laxity on muscle
      activation patterns prior to and following a lower extremity perturbation.
      Participants were subjected to a forward and either internal (IR) or external
      (ER) rotation perturbation of the trunk and thigh on the weight-bearing shank.
      Pre-activity (%MVIC) before the perturbation, and reflex time (ms) and mean
      reflex amplitude (%MVIC) following the perturbation were recorded via surface
      electromyography (sEMG) in the medial and lateral gastrocnemius, hamstring and
      quadriceps muscles. Twenty-one NCAA DI intercollegiate female athletes with below
      average anterior knee laxity (3-5 mm) were compared to 21 with above average
      anterior knee laxity (7-14 mm) as measured by a standard knee arthrometer. Groups
      differed in reflex timing by muscle (P = 0.013), with females with above average
      knee laxity (KT((>7 mm))) demonstrating a 16 ms greater delay in biceps femoris
      reflex timing compared to females with below average knee laxity (KT((<5 mm))).
      Groups also differed in muscle activation amplitude by response, muscle and
      direction of rotation (i.e. a 4-way interaction; P = 0.027). The magnitude of
      change from pre to post perturbation was significantly less in KT((>7 mm)) vs.
      KT((<5 mm)) for the medial (MG) and lateral (LG) gastrocnemius muscles, primarily
      due to higher levels of muscle preactivity while awaiting the perturbation (MG =
      20% vs. 12% MVIC, P = 0.05; LG = 33% vs. 21% MVIC, P = 0.11). Further, KT((>7
      mm)) demonstrated higher activation levels in the biceps femoris than KT((<5 mm))
      (47% vs. 27% MVIC; P = 0.025) regardless of response (pre vs. post perturbation)
      or direction of rotation. These findings suggest females with increased knee
      laxity may be less sensitive to joint displacement or loading (delayed reflex),
      and are more reliant on active control of the gastrocnemius and biceps femoris
      muscles to potentially compensate for reduced passive joint stability.

PMID- 15165598
TI  - Influence of knee angle and individual flexibility on the flexion-relaxation
      response of the low back musculature.
AB  - In many occupational settings (e.g. agriculture and construction) workers are
      asked to maintain static flexed postures of the low back for extended periods of
      time. Recent research indicates that the resulting strain in the viscoelastic,
      ligamentous tissues may have a deleterious effect on the stability of the spine
      and the normal reflex response of spinal tissues. The purpose of this study was
      to evaluate the previously described flexion-relaxation response in terms of the
      interactive effect of trunk flexion angle (30 degrees, 50 degrees, 70 degrees, 90
      degrees ), knee flexion angle (0 degrees (straight knees), 20 degrees, 40 degrees
      ) and individual flexibiliteky (low, medium, and high). These conditions were
      tested under two levels of loading: no load (just supporting the weight of the
      torso) and trunk extension moment equal to 50% of the subject's posture-specific
      maximum voluntary trunk extension capacity. Surface electromyographic (EMG) data
      were collected from the multifidus, the longissimus, the iliocostalis, the vastus
      medialis, the rectus femoris, the vastus lateralis, the biceps femoris, and the
      gastrocnemius-soleus group from a sample of eight male participants as they
      performed isometric weight holding tasks in the postures defined by the
      combinations of trunk angle and knee angle. The results of this study showed that
      knee angle did have a significant effect on the lumbar extensor muscle activity
      but only consistently at the 90 degrees trunk angle. Participant flexibility
      showed a consistent trend of decreasing lumbar extensor muscle activity with
      decreased flexibility across all trunk angle values. Most interesting was the
      interactive response of flexibility and knee angle, wherein the flexibility of
      the participant influenced the trunk angles at which the knee flexion angle
      affected the flexion-relaxation response. Highly flexible subjects showed an
      effect of knee angle on the flexion-relaxation response only at the 90 degrees
      trunk angle; subjects in the medium flexibility category showed a similar
      response in both the 70 degrees and 90 degrees trunk angles; subject in the low
      flexibility group showed no knee angle effect on the flexion-relaxation response.
      Overall the results confirm previous results with regard to the contribution of
      the passive tissues to the overall trunk extension moment but also show that the
      tension in the bi-articular biceps femoris, which was influenced by knee flexion
      angle and flexibility, affects the ratio of active extensor moment contributions
      of the lumbar extensor musculature to passive extensor moment contributions from
      the muscular and ligamentous tissues. The results of this study provide empirical
      data describing this complicated, interactive response.

PMID- 15165599
TI  - Patellar taping increases vastus medialis oblique activity in the presence of
      patellofemoral pain.
AB  - A common rehabilitation strategy for patellofemoral pain syndrome (PFPS), which
      lacks scientific evidence, includes pulling the patella medially with tape to
      reduce pain and increase the vastus medialis oblique (VMO) muscle activity. The
      purpose of this study was to examine the effect of various patellar taping
      procedures on force production, EMG activity of the VMO and vastus lateralis (VL)
      muscles, and perceived pain experienced by 30 women (27.3 +/- 1.53), half
      diagnosed with PFPS. The perceived pain, force, and EMG of the VMO and VL, were
      recorded while subjects performed maximal isokinetic leg presses at 30 degrees /s
      for each of the following patellar taping conditions: no tape (control), no glide
      (placebo), medial and lateral glide (experimental). The medial and placebo
      procedures significantly (P < 0.01) reduced perceived pain (70-80%) in PFPS
      subjects. Although patellar taping did not influence leg press force (P > 0.05),
      it increased the VMO activity and decreased the VL activity in PFPS subjects but
      had the opposite effect in healthy subjects. The findings suggest that taping the
      patella medially can contribute positively to PFPS rehabilitation. Because the
      medial glide and placebo taping conditions had similar effects, it is proposed
      that the benefits of patellar taping are not due to a change in patellar position
      but rather due to enhanced support of the patellofemoral ligaments and/or pain
      modulation via cutaneous stimulation.

PMID- 15165600
TI  - The effects of bipolar electrode montage on conduction velocity estimation from
      the surface electromyogram.
AB  - This study examines the influence of the bipolar electrode montage on conduction
      velocity (CV) estimation. Electrode montage refers to the combination of two
      parameters, the inter-electrode distance (IED), the distance between the two
      electrodes of a bipolar pair, and the inter-signal distance (ISD), the distance
      between two bipolar signals used to calculate CV. Data from the biceps brachii
      (BB) and tibialis anterior (TA) of healthy subjects are analysed. Two approaches
      are used for CV estimation. The first returns a single value per epoch. The
      second is based on finding velocity values from individual peaks in the signal
      and results in a peak velocity (PV) distribution being generated per epoch. It is
      concluded that CV estimation is significantly dependent on the choice of the
      (IED, ISD) electrode montage. The main results are that the electrode montage
      affects (1) the mean PV and CV estimates, (typically P < 0.001), (2) the degree
      of spatial variability, and (3) the width of the PV distributions. The
      combination of a small IED and large an ISD is recommended.

PMID- 15165601
TI  - Neuromechanical strategies employed to increase jump height during the initiation
      of the squat jump.
AB  - The maximal height attained in a vertical jump is heavily influenced by the
      execution of a large countermovement prior to the upward motion. When a jump must
      be executed without a countermovement, as in a squat jump, the maximal jump
      height is reduced. During such conditions, the human body may use other
      strategies in order to increase performance. The purpose of this research was to
      investigate the effects of two strategies employed during the initiation of the
      squat jump: the premovement silent period (PSP), and the small amplitude
      countermovement (SACM). Fifteen elite male volleyball players (20.6 +/- 1.6
      years) and 13 untrained males (20.2 +/- 1.7 years) performed 10 maximal effort
      squat jumps from identical starting positions. The electromyographic activity of
      the vastus lateralis and biceps femoris was measured in conjunction with the
      vertical ground reaction force and vertical displacement. It was found that the
      presence of a PSP or a SACM of 1-3 cm did not increase maximal squat jump height
      significantly (p > 0.05), in neither the highly trained athletes nor the
      untrained individuals. These results suggest that these strategies do not play a
      major role in the determination of jump height. Researchers have assumed that a
      squat jump is purely concentric, and that there are no facilitating mechanisms
      present that may influence the performance of the jump. This study provides
      evidence to support this assumption.

PMID- 15165602
TI  - Did trypanosomatid parasites have photosynthetic ancestors?
AB  - Some molecular phylogenies of plastid-like genes suggest that chloroplasts (the
      structures responsible for photosynthesis in plants and algae) might have been
      secondarily lost in trypanosomatid parasites. Chloroplasts are present in some
      euglenids, which are closely related to trypanosomatids, and it has been argued
      that chloroplasts arose early in the diversification of the lineage Euglenozoa,
      to which trypanosomatids and euglenids belong (plastids-early hypothesis). This
      article reviews how euglenid ultrastructural systems are functionally integrated
      and phylogenetically correlated. I argue that chloroplast acquisition profoundly
      altered the structure of certain euglenids, and that the complete absence of
      these modifications in other euglenozoans is most consistent with their never
      having had a chloroplast. Ultrastructural evidence suggests that chloroplasts
      arose relatively recently within a specific subgroup of euglenids and that
      trypanosomatids are not secondarily non-photosynthetic (plastids-recent
      hypothesis).

PMID- 15165603
TI  - The weapon potential of a microbe.
AB  - The designation of a microbe as a potential biological weapon poses the vexing
      question of how such a decision is made given the many pathogenic microbes that
      cause disease. Analysis of the properties of microbes that are currently
      considered biological weapons against humans revealed no obvious relationship to
      virulence, except that all are pathogenic for humans. Notably, the weapon
      potential of a microbe rather than its pathogenic properties or virulence
      appeared to be the major consideration when categorizing certain agents as
      biological weapons. In an effort to standardize the assessment of the risk that
      is posed by microbes as biological warfare agents using the basic principles of
      microbial communicability (defined here as a parameter of transmission) and
      virulence, a simple formula is proposed for estimating the weapon potential of a
      microbe.

PMID- 15165604
TI  - Evolutionary significance of stress-induced mutagenesis in bacteria.
AB  - Mutagenesis is often increased in bacterial populations as a consequence of
      stress-induced genetic pathways. Analysis of the molecular mechanisms involved
      suggests that mutagenesis might be increased as a by-product of the stress
      response of the organism. By contrast, computer simulations and analyses of
      stress-inducible phenotypes among natural isolates of Escherichia coli suggest
      that stress-induced mutagenesis (SIM) could be the result of selection because of
      the beneficial mutations that such a process can potentially generate. Regardless
      of the nature of the selective pressure acting on SIM, it is possible that the
      resulting increased genetic variability plays an important role in bacterial
      evolution.

PMID- 15165605
TI  - Multistep entry of rotavirus into cells: a Versaillesque dance.
AB  - Rotavirus entry into a cell is a complex multistep process in which different
      domains of the rotavirus surface proteins interact with different cell surface
      molecules, which act as attachment and entry receptors. These recently described
      molecules include several integrins and a heat shock protein, which have been
      found to be associated with cell membrane lipid microdomains. The requirement
      during viral entry for several cell molecules, which might be required to be
      present and organized in a precise fashion, could explain the selective cell and
      tissue tropism of these viruses. This review focuses on recent data describing
      the virus-receptor interactions, the role of lipid microdomains in rotavirus
      infection and the mechanism of rotavirus cell entry.

PMID- 15165606
TI  - Norovirus disease: changing epidemiology and host susceptibility factors.
AB  - Noroviruses cause the majority of acute viral gastroenteritis cases that occur
      worldwide. The increased recognition of noroviruses as the cause of outbreaks and
      sporadic disease is due to the recent availability of improved norovirus-specific
      diagnostics. Transmission of these viruses is facilitated by their high
      prevalence in the community, shedding of infectious virus particles from
      asymptomatic individuals and the high stability of the virus in the environment.
      Currently, the spectrum of clinical disease and the understanding of host
      susceptibility factors are changing. Cases of chronic norovirus gastroenteritis
      have been observed in transplant recipients and unusual clinical presentations
      have been recognized in otherwise healthy adults that are under physical stress.
      Recently, noroviruses were found to bind to gut-expressed carbohydrates, leading
      to a correlation between a person's genetically determined carbohydrate
      expression and their susceptibility to Norwalk virus infection. Greater community
      surveillance and further investigation of carbohydrate receptor-binding
      properties could provide further insights into norovirus transmission,
      susceptibility and pathogenesis, and should aid in developing vaccines and
      antiviral therapies for this common viral disease.

PMID- 15165608
TI  - Invasin and beyond: regulation of Yersinia virulence by RovA.
AB  - RovA, a member of the MarR/SlyA family of winged-helix transcription factors,
      regulates expression of invasin, the major adhesion and invasion factor in
      Yersinia enterocolitica and Yersinia pseudotuberculosis. Disruption of rovA
      increases the LD(50) of the organism when inoculated using the oral route.
      However, when administered by intraperitoneal injection only a slight difference
      in LD(50) between mutant and wild-type organisms is apparent. The study of RovA
      and the genes it regulates provides a unique opportunity to gain insight into the
      initial stages of a Yersinia infection.

PMID- 15165607
TI  - Error-prone replication for better or worse.
AB  - Precise genome duplication requires accurate copying by DNA polymerases and the
      elimination of occasional mistakes by proofreading exonucleases and mismatch
      repair enzymes. The commonly held belief that 'if something is worth doing, then
      it's worth doing well' normally applies to DNA replication and repair, however,
      there are exceptions. This review describes elements that are crucial to cell
      fitness, evolution and survival in the recently discovered error-prone DNA
      polymerases. Large numbers of errant DNA polymerases, spanning microorganisms to
      humans, are used to rescue stalled replication forks by copying damaged DNA and
      even undamaged DNA to generate 'purposeful' mutations that generate genetic
      diversity in times of stress. Here we focus on low-fidelity polymerases from
      bacteria, comparing Escherichia coli, archeabacteria and those most recently
      discovered in Gram-positive Bacilli, Streptococcus, pathogenic Mycobacterium and
      intein-containing cyanobacteria.

PMID- 15165610
TI  - Higher obesity risk associated with the exon-8 insertion of the UCP2 gene in a
      Spanish case-control study.
AB  - OBJECTIVE: We conducted a case-control study to examine the association between
      the risk of obesity and the exon-8 insertion allele in the UCP2 gene. METHODS:
      The case series included 157 subjects with a body mass index greater than 30
      kg/m(2) (obesity) and no other major disease except for type 2 diabetes; the
      control series consisted of 150 healthy subjects with a body mass index less than
      25 kg/m(2). In total, 307 subjects between ages 20 and 60 y were screened for the
      exon-8 insertion allele in the UCP2 gene. RESULTS: The association between risk
      of obesity and the UCP2 insertion allele was estimated using multivariate
      logistic regression. Obesity risk among carriers of the UCP2 insertion allele was
      slightly higher than among non-carriers (unadjusted odds ratio, 1.42; 95%
      confidence interval, 0.90 to 2.23); however, when the model was adjusted for sex,
      age, physical activity, and sedentary lifestyle (hours spent sitting down), a
      statistically significant odds ratio of obesity (1.94; 95% confidence interval,
      1.14 to 3.30; P = 0.01) for carriers of the UCP2 insertion allele was found.
      CONCLUSIONS: We found a greater risk of developing obesity among individuals
      carrying the exon-8 insertion allele in the UCP2 gene, independent of sex, age,
      physical activity, and sedentary lifestyle, which may partly explain some
      discrepancies found in the literature.

PMID- 15165611
TI  - Associations between sociodemographic and lifestyle factors and dietary quality
      among adolescents in Palma de Mallorca.
AB  - OBJECTIVE: We assessed associations between sociodemographic and lifestyle
      factors and dietary quality among adolescents. METHODS: Subjects were 445
      adolescents (171 boys, 274 girls; 14 to 18 y old) selected from the Palma de
      Mallorca (Balearic Islands, Spain) school census (96% participation) using two
      stage probability sampling. The study protocol included dietary intake by means
      of a validated semiquantitative food-frequency questionnaire; sociodemographic
      factors of sex, maternal level of education, parental occupational status, and
      maternal region of origin; physical activity; and body weight and height
      measurements. Body mass index was calculated and energy intake expressed as
      multiples of basal metabolic rate. RESULTS: Mean daily energy intakes were 12.9
      MJ for boys and 12.0 MJ for girls. Boys showed a higher percentage of energy from
      carbohydrates but a lower percentage from proteins and fat than did girls (44.9
      versus 41.6, 18.8 versus 19.8, and 36.3 versus 38.5, respectively). Dietary fiber
      intake was within the recommended levels. Mineral and vitamin intakes generally
      met their estimated needs, except for vitamins A and D, which covered less than
      two-thirds of the recommended intake. Maternal educational level was positively
      correlated with dietary mineral and vitamin intakes. A positive relation between
      physical activity and dietary intakes of carbohydrate and of mineral and vitamin
      was found. CONCLUSIONS: Maternal level of education and physical activity are
      associated to the quality of diet among adolescents in Palma de Mallorca.

PMID- 15165612
TI  - Dietary virgin olive oil triacylglycerols as an independent determinant of very
      low-density lipoprotein composition.
AB  - OBJECTIVE: We examined the effects of virgin olive oil (VOO) triacylglycerols
      (TGs) on the lipid composition of human very low-density lipoprotein (VLDL).
      METHODS: Twenty-one normocholesterolemic, normotensive, non-diabetic elderly
      subjects were recruited for the study. Two VOOs (VOO1 and VOO2) of the same
      variety, with an equivalent composition in minor components and differing only in
      the oleic and linoleic acid concentrations, were administered for 4 wk each to
      assess the effect of their TG molecular species compositions. Blood was collected
      after an overnight fast, VLDLs were isolated by ultracentrifugation, and lipid
      classes, TG molecular species, and TG fatty acid composition were determined.
      RESULTS: Dietary VOOs significantly differed in TG molecular species composition.
      VOO1 represented larger amounts of triolein (P < 0.01), whereas VOO2 was
      significantly enriched with dilinoleoyl-oleoyl-glycerol, linoleoyl-dioleoyl
      glycerol, and linoleoyl-oleoyl-palmitoyl-glycerol (P < 0.01). For VLDL, intake of
      VOO1 caused an increase of total TG (P < 0.01) due mainly to increases in
      triolein and linoleoyl-dioleoyl-glycerol. Conversely, VOO2 increased VLDL
      cholesteryl esters (P < 0.01) and TG rich in arachidonic acid (P < 0.01).
      CONCLUSIONS: The different TG molecular species compositions of dietary oils may
      be an independent determinant of the lipid composition of VLDL in elderly people
      and therefore may play a role in regulating lipoprotein metabolism in these
      subjects.

PMID- 15165614
TI  - Cardiovascular effects of milk enriched with omega-3 polyunsaturated fatty acids,
      oleic acid, folic acid, and vitamins E and B6 in volunteers with mild
      hyperlipidemia.
AB  - OBJECTIVE: Results from epidemiologic studies and clinical trials have indicated
      that consumption of omega-3 fatty acids, oleic acid, and folic acid have
      beneficial effects on health, including decreased risk of cardiovascular disease.
      We evaluated the combined effects of these nutrients through the consumption of
      milk enriched with omega-3 polyunsaturated fatty acids, oleic acid, vitamins E
      and B6, and folic acid on risk factors for cardiovascular disease in volunteers
      with mild hyperlipidemia. METHODS: Thirty subjects ages 45 to 65 y (51.3 +/- 5.3
      y) were given 500 mL/d of semi-skimmed milk for 4 wk and then 500 mL/d of the
      enriched milk for 8 wk. Plasma and low-density lipoproteins were obtained at the
      beginning of the study and at 4, 8, and 12 wk. RESULTS: Consumption of enriched
      milk for 8 wk increased plasma concentrations of docosahexaenoic acid and
      eicosapentaenoic acid and significantly (P < 0.05) decreased plasma
      concentrations of triacylglycerol (24%), total cholesterol (9%), and low-density
      lipoprotein cholesterol (13%). Plasma and low-density lipoprotein oxidation and
      vitamin E concentration remained unchanged throughout the study. Significant
      decreases in plasma concentrations of vascular cell adhesion molecule-1 (9%) and
      homocysteine (17%) were found, accompanied by a 98% increase in plasma
      concentration of folic acid. CONCLUSIONS: Dairy supplementation strategies with
      omega-3 polyunsaturated fatty acids, oleic acid, and vitamins may be useful for
      decreasing risk factors for cardiovascular disease.

PMID- 15165613
TI  - L-ornithine alpha-ketoglutarate in HIV infection: effects on muscle,
      gastrointestinal, and immune functions.
AB  - OBJECTIVES: There have been claims that l-ornithine alpha-ketoglutarate (OKG)
      exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed
      at quantifying the effects of OKG on muscle force, body composition, and immune
      function in outpatients infected with the human immunodeficiency virus (HIV) and
      presenting weight loss. METHODS: Forty-six HIV(+) patients were included in a
      double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG
      or isonitrogenous placebo and nutritional counseling). Podometry, handgrip
      strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance,
      3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and
      gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk. RESULTS: At
      baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/-
      172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10)
      copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss
      (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808
      kcal/d). Twenty-nine patients completed the protocol. Both groups increased their
      body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P <
      0.01 versus baseline). They showed a similar positive correlation between
      handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms
      increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No
      other differences were observed between groups. CONCLUSIONS: All patients
      increased their body mass index and triceps skinfold thickness due to food
      supplementation and diet counseling. Oral OKG failed to improve nutritional,
      functional, or immunologic status in these weight-losing HIV(+) patients and had
      important gastrointestinal side effects.

PMID- 15165615
TI  - Parenteral nutrition practices in hospital pharmacies in Switzerland, France, and
      Belgium.
AB  - OBJECTIVE: Important changes in administering total parenteral nutrition (PN)
      admixtures have occurred over the past decade. This study describes hospital
      pharmacists' practices in France (F), Switzerland (CH), and Belgium (B). METHODS:
      From the responses received using a standardized questionnaire, (n = 378) we
      determined the origin, types of container used, and choice of PN formula
      (standard versus tailor-made) and the type of quality control and the existence
      of nutrition support teams. RESULTS: The mean response rates were 55.6% (CH),
      30.5% (F), and 24.5% (B). Standard formulas were used mainly for adult patients
      (CH, 86%; F, 79%; B, 86%), whereas approximately 50% of tailor-made PN bags were
      used for children. Single-compartment or multicompartment bags or glass bottles
      contained standard formulas. Most standard formulas were provided by industry,
      apart from (B), where 50% of PN solutions were compounded by hospital pharmacies.
      Single-compartment bags contained generally tailor-made formulas produced
      exclusively by hospital pharmacies in (CH) and (B), whereas 33% were provided by
      industry in (F). Quality controls were mostly visual and occurred in 75% to 95%
      of hospitals. Nutrition support teams were present in 32% to 45% of hospitals.
      CONCLUSION: The choice, origin, and type of container used for PN formulas were
      highly variable among countries. However, the use of standard formulas in bags
      was predominant in (CH) and (B). The function of nutrition support teams was
      similar in (F), (CH), and (B).

PMID- 15165616
TI  - Dietary virgin olive oil enhances secretagogue-evoked calcium signaling in rat
      pancreatic acinar cells.
AB  - OBJECTIVE: We evaluated the long-term effects of a fat-enriched diet (virgin
      olive oil) on calcium mobilization and amylase secretion induced by
      cholecystokinin-octapeptide (CCK-8) in rat pancreatic acinar cells. Olive oil is
      a major component of the Mediterranean diet, and its role in human health is
      actively being debated. METHODS: Weaning male Wistar rats (21 d old) were
      assigned to one of two experimental groups and fed for 8 wk with a commercial
      chow (control group) or an experimental diet (olive group) containing 100 g/kg of
      virgin olive oil as dietary fat. Intracellular free calcium [Ca(2+)](i) levels
      were determined by loading the pancreatic cells with the fluorescent ratio-metric
      calcium indicator Fura-2 on an inverted fluorescent microscope. For measurement
      of amylase secretion, cells were incubated with the appropriate secretagogue for
      30 min, and amylase activities in the supernatant were determined by the Phadebas
      blue starch method. Analysis of variance was used to test differences between
      groups. RESULTS: Compared with the control group, the CCK-8-induced increase in
      [Ca(2+)](i) occurred in cells from rats in the olive group (P < 0.05). This
      stimulatory effect of dietary virgin olive oil was observed in calcium
      oscillations and large [Ca(2+)](i) transients induced by low (20 pM/L) and high
      (10 nM/L) concentrations of CCK-8, respectively. In addition to the effects of
      dietary virgin olive oil on calcium mobilization, it increased (P < 0.05) amylase
      secretion in response to CCK-8. Olive oil treatment did not significantly alter
      resting [Ca(2+)](i) or amylase release values compared with the control group.
      Similar results were obtained when pancreatic acinar cells were stimulated with a
      high concentration of acetylcholine (10 microM/L). CONCLUSION: The present
      results demonstrate that a diet supplemented with virgin olive oil can modify
      pancreatic cell function as assessed by [Ca(2+)](i) mobilization and amylase
      release evoked by secretagogues in rat pancreatic acinar cells. A role for fatty
      acids in calcium signaling is suggested.

PMID- 15165617
TI  - Classic dengue fever affects levels of circulating antioxidants.
AB  - OBJECTIVE: We studied alterations of circulating antioxidant nutrients in
      patients with classic dengue fever in the tropical lowlands of Guatemala.
      METHODS: In nine patients with dengue fever and 12 healthy Guatemalan control
      subjects, we assessed plasma concentrations of retinol, alpha-tocopherol, beta
      carotene, glutathione, taurine, thiobarbituric acid-reactive species, and total
      antioxidant status. Control subjects were assessed twice within 48 h to account
      for day-to-day variations. Febrile patients with dengue fever were examined on
      the day of admission to the hospital, at discharge after defervescence
      (approximately 5 d after admission), and 7 d thereafter. RESULTS: In patients
      with dengue fever, increases in plasma concentrations of retinol and beta
      carotene were seen, whereas decreases were observed for glutathione and total
      antioxidant status. As compared with the reference group, patients with dengue
      fever had lower retinol concentrations in the acute phase of the disease and
      lower glutathione concentrations 7 d after discharge. Further, thiobarbituric
      acid-reactive species levels were higher in the dengue fever patients as analyzed
      by unpaired t test. CONCLUSION: Using dengue fever as a model for the metabolic
      response to an acute, self-limited tropical viral infection, the present findings
      suggest slight turbulence of the antioxidant system that may be a response to or
      a consequence of the viral inflammatory process.

PMID- 15165618
TI  - Nutritional intervention in pressure ulcer guidelines: an inventory.
AB  - Nutritional data from the literature and the high prevalence of malnutrition in
      patients at risk of pressure ulcers (PUs) or with established PU mandate
      structural nutritional actions in these patients. Guidelines can help to improve
      nutritional alertness in professionals and promote structural nutritional
      assessment and nutritional intervention in PU-prone or PU patients. PU guidelines
      from 13 countries were compared with regard to nutritional management of PU
      patients. The attention paid to nutritional prevention and treatment in PU
      patients varied considerably across guidelines. Recommendations with regard to
      nutritional intervention should be incorporated transparently into PU guidelines
      and should be complete, specific, testable, and cover the entire nutritional
      cycle.

PMID- 15165620
TI  - Evidence for relatively greater subcutaneous fat deposition in stunted girls in
      the North West Province, South Africa, as compared with non-stunted girls.
AB  - OBJECTIVE: We examined differences in body composition between stunted and non
      stunted girls, with adjustments for confounding factors. METHODS: A cross
      sectional study was conducted in a representative sample of 478 African school
      girls, ages 10 to 15 y, in the North West Province, South Africa. Height, weight,
      skinfold thicknesses, and waist and mid upper arm circumferences were measured by
      trained biokineticists using standard methods. Trained field workers measured
      dietary intakes by 24-h recall, and physical activity was measured by using the
      physical activity recall of the previous day. Body mass index and physical
      activity category were calculated. RESULTS: Stunted girls had significantly lower
      weight and skinfold thicknesses than did non-stunted ones. After including the
      covariates: age, years since menarche, school, type of housing, dietary energy
      and fat intakes, physical activity category, body weight, and stratum of
      urbanization in analysis of variance, the mean sum of triceps skinfold and
      subscapular skinfold thicknesses of stunted girls was greater than that of the
      non-stunted girls (P < 0.002). Stunted subjects were less active than non-stunted
      ones. CONCLUSION: This manifestation of relatively more subcutaneous fat and
      greater waist circumference in stunted girls may be involved in the development
      of obesity among black women in South Africa.

PMID- 15165619
TI  - Changes in serum lipoprotein lipids and their fatty acid compositions and lipid
      peroxidation in growing rats fed soybean protein versus casein with or without
      cholesterol.
AB  - OBJECTIVE: We compared the effects of diets based on soybean protein and casein
      supplemented or not supplemented with 0.1% cholesterol on plasma lipoprotein
      lipid amounts and their fatty acid compositions, lecithin:cholesterol acyl
      transferase activity, and lipid peroxidation. METHODS: The composition and
      concentration of lipid and apolipoprotein in different lipoprotein classes,
      plasma LCAT activity, and lipid peroxidation were determined in rats fed 20%
      highly purified soybean protein or casein with or without 0.1% cholesterol for 2
      mo. RESULTS: Soybean protein and casein diets with or without cholesterol had
      similar plasma total cholesterol concentrations. Soybean protein consumption
      diminished very low-density lipoprotein particle number, as measured by
      diminished contents of very low-density lipoprotein triacylglycerol,
      phospholipid, and apolipoprotein-B100. Lecithin:cholesterol acyl-transferase
      activity was not significantly modified by either protein. The soybean protein
      diet decreased the linoleate desaturation index (20:4[omega-6]/18:2[omega-6]) in
      liver and high-density lipoprotein fraction 2-3-phospholipids but enhanced red
      blood cell resistance against free radical attack. Addition of cholesterol to
      both protein diets decreased concentrations of high-density lipoprotein fraction
      2-3 cholesterol. Lecithin:cholesterol acyl-transferase activity tended to be
      greater after cholesterol feeding, likely due to the enhanced high-density
      lipoprotein fraction 2-3 apolipoprotein-AI, a cofactor activator for
      lecithin:cholesterol acyl-transferase. Regardless of dietary protein source,
      cholesterol supplementation decreased the linoleate desaturation index in liver
      and plasma lipoprotein lipids and red blood cell resistance to free radical
      attack. CONCLUSIONS: Our results suggest that the dietary protein origin affects
      lipid peroxidation and polyunsaturated fatty acid biosynthesis and distribution
      among liver and different lipoprotein lipid classes, but plays only a minor role
      in the regulation of plasma and lipoprotein cholesterol concentrations. Providing
      dietary cholesterol (0.1%) with casein or soybean protein attenuates the effects
      of these proteins, with the exception of plasma cholesterol.

PMID- 15165621
TI  - Isomers of trans fatty acids modify the activity of platelet 12-P lipoxygenase
      and cyclooxygenase/thromboxane synthase.
AB  - OBJECTIVES: Trans isomers of fatty acids (TFA) have been implicated in the
      initiation and progression of atherosclerosis. Previous studies have shown that
      trans-unsaturated fatty acids like their cis-unsaturated counterparts exert a
      modifying effect on platelet aggregation. The aim of this work was to determine
      the influence of TFA on the aforementioned enzymes: lipoxygenase and
      cyclooxygenase/thromboxane synthase. METHODS: Two C18 cis-trans fatty acid pairs:
      oleic/elaidic and linoleic/linolelaidic were chosen. Fasting blood was sampled
      from 30 healthy volunteers without any lipid abnormalities and not on medication
      for at least 7 days prior to sampling. Platelet-rich plasma (PRP) was prepared
      and the platelet count was adjusted to 3 x 10(8) cells x ml(-1). Fatty acids in
      hexane were added to a final concentration of 7 microM and evaporated to dryness
      under nitrogen, 500 microl of PRP was pipetted into each tube, thoroughly mixed
      and incubated at 37 degrees C for 60 min. 12-P LOX activity was measured with a
      spectrophotometric method and expressed per mg protein.
      Cyclooxygenase/thromboxane synthase activity was determined by TXB(2) production
      with an ELISA-based assay. Statistics were done with the Kruskal-Wallis test and
      Statistica software package. RESULTS: We have found that the activity of 12-P LOX
      was suppressed by all cis-trans fatty acids used by us.
      Cyclooxygenase/thromboxane synthase activity was significantly inhibited by
      polyunsaturated fatty acids only. Linolelaidic acid was more potent in comparison
      to its monounsaturated (elaidic acid) counterpart. CONCLUSIONS: We believe that
      the effects of fatty acids are demonstrated at the membrane level where fatty
      acids may produce a perturbation in specific lipid domains. TFA are able to
      interact with the platelet membrane and transmembrane proteins just as the cis
      isomers. By interacting with proteins exposed on the cytoplasmic membrane, TFA
      may modify the activity of receptors and other membrane proteins. In this way,
      changes on the membrane surface are propagated into the cell affecting the
      activity of cytoplasmic enzymes like 12-P LOX and cyclooxygenase/thromboxane
      synthase.

PMID- 15165622
TI  - John M. Kinney International Award for Pediatric Nutrition. Use of fermented
      foods to combat stunting and failure to thrive: background of the study.

PMID- 15165623
TI  - John M. Kinney International Award for Nutrition and Metabolism. Lactobacilli and
      fibers--a strong couple against bacterial infections in patients with major
      abdominal surgery.

PMID- 15165624
TI  - John M. Kinney International Award for Nutrition and Metabolism. Specific
      nutrient: role of arginine in sepsis.

PMID- 15165625
TI  - John M. Kinney International Award for General Nutrition. Glutamine, heat shock
      protein, and inflammation--opportunity from the midst of difficulty.

PMID- 15165626
TI  - John M. Kinney International Award for General Nutrition. A story of our work.

PMID- 15165627
TI  - Keeping up the defenses.

PMID- 15165628
TI  - Selenium: the Se-XY nutraceutical.

PMID- 15165629
TI  - Adjusting for confounding.

PMID- 15165630
TI  - Sturge-Weber syndrome: a review.
AB  - Sturge-Weber syndrome is a rare disorder that occurs with a frequency of
      approximately 1 per 50,000. The disease is characterized by an intracranial
      vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital
      and posterior parietal lobes. Facial cutaneous vascular malformations, seizures,
      and glaucoma are among the most common symptoms and signs. Stasis results in
      ischemia underlying the leptomeningeal angiomatosis, leading to calcification and
      laminar cortical necrosis. The clinical course is highly variable and some
      children experience intractable seizures, mental retardation, and recurrent
      strokelike episodes. In this review, we describe the syndrome's characteristic
      features, clinical course, and optimal management.

PMID- 15165632
TI  - Unconsciousness and delirious behavior in children with febrile seizures.
AB  - The aim of this study is to clarify the incidence and clinical features of
      prolonged unconsciousness and delirious behavior in children with febrile
      seizures. We studied 213 consecutive febrile seizures during 208 febrile episodes
      in 203 patients. The seizure manifestations, the duration of seizures, the
      duration of unconsciousness, and the presence or absence of delirious behavior
      were determined on the basis of interviews with the parents with the assistance
      of medical records. The duration of seizures was less than 5 minutes in 90.2% of
      the seizures. The duration of unconsciousness was less than 30 minutes in 93% of
      the seizures. Delirious behavior was observed in 2.0% of the patients. Delirious
      behavior appeared before febrile seizures, and its duration was not long. On
      multiple regression analysis, nongeneralized seizures, seizures of >/=5 minutes,
      and intravenous diazepam were demonstrated to be independently associated with
      prolonged unconsciousness. In conclusion, prolonged unconsciousness and delirious
      behavior are rare in children with febrile seizures. Careful diagnostic
      evaluation is necessary when a child with febrile seizures has associated
      prolonged unconsciousness or delirious behavior.

PMID- 15165631
TI  - Predicting outcome of initial treatment with carbamazepine in childhood focal
      epilepsy.
AB  - We developed a model to predict the outcome of treatment with carbamazepine in
      children with newly diagnosed focal epilepsy of presumed temporal lobe origin,
      using data available at the time of diagnosis. Eligible children observed at The
      Children's Hospital of Philadelphia during 1999 were identified. Data were
      abstracted on four potential predictor variables for carbamazepine success or
      failure. A total of 149 patients completed an adequate first antiepileptic trial.
      Carbamazepine was the initial drug used in 129 (87%) patients. Forty-one of these
      129 patients (32%) had persistent seizures. Significant predictors of initial
      carbamazepine failure were as follows: early risk factor for epilepsy (risk ratio
      = 3.1 [95% confidence interval 1.6, 4.0]) and temporal lobe abnormality on
      magnetic resonance imaging scan (risk ratio = 3.1 [1.7, 4.2]). The outcome of the
      initial carbamazepine trial was correctly classified in up to 78% of patients.
      Accurate prediction of initial carbamazepine failure was as high as 0.67 (0.53,
      0.79). Accurate prediction of initial carbamazepine success was as high as 0.87
      (0.77, 0.94). In this study, standard clinical data were less than adequate for
      predicting response to the initial trial of carbamazepine, with prediction of
      carbamazepine failure being particularly difficult. Better markers of
      antiepileptic response and nonresponse are required to guide optimal therapy in
      patients with epilepsy.

PMID- 15165633
TI  - Masseter reflex in childhood and adolescence.
AB  - We report normative data of masseter reflex from a group of 54 children 2-16
      years of age. For statistical analysis, the patients were divided into five age
      groups: 2-4, 5-7, 8-10, 11-13, and 14-16 years of age. A tap to the chin, using a
      hammer with a trigger device, elicited the masseter reflex. The response was
      recorded by surface electrodes. The onset latency and peak-to-peak amplitude of
      the averaged curve of eight reflex responses were measured. The reflex response
      could be recorded in all children and adolescents of all groups. The mean latency
      shortened from age 2 to 7 and was stable at the age of 8 years. As a sign of
      maturation, the increase of amplitude corresponded to the shortening of latency
      and was also stable at the age of 8 years. Abnormal side differences in latency
      of 0.9 ms (age group 2-4 years), 1.1 ms (age group 5-7 years), and 0.8 ms (age
      group 8-16 years) were evaluated. An amplitude ratio (lower amplitude divided by
      higher one) above 0.33 was calculated as normal.

PMID- 15165634
TI  - Acute disseminated encephalomyelitis: an MRI/MRS longitudinal study.
AB  - A clinical and radiologic diagnosis of acute disseminated encephalomyelitis was
      made in two children: a 6-month-old female who presented with focal seizures and
      thalamic and cerebral white matter lesions, and a 4.5-year-old male who presented
      with tremor and dystonia and had bilateral basal ganglia lesions, without
      evidence of active brain infection. Serial clinical and laboratory evaluations
      were supplemented by neuroimaging including routine magnetic resonance imaging
      and (1)H magnetic resonance spectroscopy. They were treated symptomatically,
      without using steroids or intravenous immunoglobulin, and both children
      recovered. Single voxel (1)H magnetic resonance spectroscopy data were acquired
      from the involved areas and from normal-appearing white matter. Abnormalities in
      N-acetyl-aspartate, choline, and lactate peaks were evident during the
      symptomatic phase, and persistence of low N-acetyl-aspartate was observed during
      recovery. These spectroscopic findings are consistent with neuropathologic
      findings of neuronal dysfunction, cellular membrane turnover, cellular
      infiltration, and metabolic stress in the acute phase, and with neuronal loss in
      the chronic phase.

PMID- 15165635
TI  - Divalproex-ER pharmacokinetics in older children and adolescents.
AB  - Valproic acid pharmacokinetic profile and tolerability after administration of
      divalproex sodium extended-release tablets was characterized in older children
      and adolescents. In this multiple-dose, open-label, pharmacokinetic study, the
      patients were divided into two age groups, 8-11 years (older children; n = 15)
      and 12-17 years (adolescents; n = 14). Once-daily administration of divalproex
      sodium extended-release tablets (doses ranged from 250 to 1750 mg) in older
      children and adolescents produced relatively flat plasma valproic acid
      concentration-time profiles over the entire 24-hour dosing interval, similar to
      the pharmacokinetic performance of this formulation in adults. The mean (standard
      deviation) oral clearance values for unbound valproic acid were 94.3 (51.8) and
      82.3 (28.2) mL/h/kg and for total valproic acid were 11.2 (3.77) and 9.06 (2.03)
      mL/h/kg in older children and adolescents, respectively. Two patients
      discontinued for administrative reasons, whereas one discontinued for an adverse
      event (flulike syndrome). Adverse events reported by three or more patients were
      flu syndrome (5 patients, 17.2%) and headache (3 patients, 10.3%). Reported
      adverse events were generally mild to moderate in severity and similar to those
      reported in previous divalproex studies. This study demonstrates that in older
      children and adolescents, once-daily administration of divalproex sodium extended
      release tablets may potentially be used to sustain plasma valproic acid
      concentrations within the usually accepted therapeutic ranges for various
      indications.

PMID- 15165636
TI  - Pediatric neurology participation in a fetal diagnostic service.
AB  - Fetal neurologic consultations were provided to 166 maternal-fetal pairs over a 5
      year period. Consultations were initiated during the second trimester in 46%
      (74/166) of pairs. Fifty-percent (83/166) of these consultations involved brain
      malformations, of which 55% (46/83) were also associated with other organ
      abnormalities. Brain malformations principally consisted of encephalocele, dorsal
      neural tube defects, holoprosencephaly, schizencephaly, cerebellar dysgenesis,
      and ventriculomegaly. Non-central nervous system organ system anomalies were
      observed in another 50% (83/166), in decreasing order of occurrence-cardiac,
      renal, gastrointestinal, pulmonary, in utero growth restriction, and hydrops
      fetalis. Outcome data on 128 children included survival at delivery for 86/128 or
      67.2%, termination in 16/128 (12.5%), stillborn 6/128 (4.7%), and postnatal
      deaths in 20/128 (15.6%). Maternal medical histories were abnormal for 65% of
      women. Placental pathology was abnormal in 80% (72/102) of available specimens,
      consisting of both chronic and acute lesions. Postnatal diagnoses were obtained
      in 128 neonates; 64% (82/128) remained the same diagnosis, 28.1% (36/128) had a
      worse or improved diagnosis, and 10/128 (7.8%) were normal. Pediatric
      neurologists can provide useful fetal consultations early during gestation, and
      must consider multiple organ diagnoses and maternal-placental diseases. Postnatal
      diagnoses may be different from the fetal diagnoses which will influence
      continuity of care for the child at older ages.

PMID- 15165637
TI  - p75-NGFR expression in the human prenatal pituitary gland.
AB  - The aim of this study was to elucidate the distribution of nerve growth factor
      receptor (NGFR) in the prenatal human pituitary gland until 21 weeks of
      gestation. Eight fetuses, with gestational ages from 13 to 21 weeks, were
      examined. The midaxial tissue block from the cranial base, including the
      pituitary gland and the sella turcica, was excised from the fetuses. The tissue
      was decalcified, embedded in paraffin, and cut in serial sections in 4-micro
      thicknesses. Immunohistochemistry was performed with monoclonal antibody p75
      NGFR. p75-NGFR immunoreactivity was observed in fetuses from 15 weeks of
      gestation in the borderline between pars intermedia and the neurohypophysis.

PMID- 15165638
TI  - Infantile convulsions and paroxysmal choreoathetosis in a consanguineous family.
AB  - Infantile convulsions and paroxysmal choreoathetosis is a rare autosomal-dominant
      disorder characterized by variable presentation of benign infantile seizures and
      paroxysmal dyskinesia. The disease gene was mapped to chromosome 16p12-q12. We
      report a consanguineous Turkish family with three individuals affected by
      infantile convulsions and paroxysmal choreoathetosis. Two siblings whose parents
      were first cousins had benign infantile convulsions and paroxysmal
      choreoathetosis. Whereas their father presented only paroxysmal choreoathetosis.
      The siblings displayed an earlier age of onset and increased frequency of the
      paroxysmal symptoms than their father. We genotyped the pedigree with polymorphic
      microsatellite markers, spanning the pericentromeric region of chromosome 16.
      Construction of the haplotypes demonstrated the segregation of the disease with
      the infantile convulsions and paroxysmal choreoathetosis locus. The disease was
      inherited as an autosomal-dominant trait with incomplete penetrance. The affected
      father was heterozygous for the disease haplotype. However, the two affected
      siblings manifested homozygosity for the disease haplotype. By haplotype
      analysis, we confirmed the assignment of the locus for infantile convulsions and
      paroxysmal choreoathetosis to chromosome 16p12-q12 in this family, and our
      results also demonstrate that homozygotes for infantile convulsions and
      paroxysmal choreoathetosis may have a more severe form of the disease than
      heterozygotes.

PMID- 15165639
TI  - Vialetto-Van Laere syndrome in two sisters born to consanguineous parents.
AB  - Vialetto-Van Laere syndrome is a rare anterior horn cell disease affecting young
      persons. Bulbar palsy with deafness is the characteristic feature. Of the total
      35 cases reported in the literature, only one case was from India. This article
      presents the second case report from India.

PMID- 15165640
TI  - Familial retinal migraines.
AB  - Approximately 25% of sufferers of retinal migraine are thought to have a positive
      family history. Retinal migraines can cause both transient, and rarely permanent,
      unilateral monocular visual loss. This report of familial retinal migraines
      furthers our understanding of this particular migraine subtype. Two families with
      retinal migraines are reported suggesting an autosomal-dominant inheritance
      pattern with variable expression and penetrance.

PMID- 15165642
TI  - Near fatal cerebellar swelling in familial hemophagocytic lymphohistiocytosis.
AB  - We describe a 3 year-old male who presented with fever and cerebellar dysfunction
      after varicella. He developed transient hepatosplenomegaly, cytopenias, and
      progressive central nervous system involvement (coma, status epilepticus, and
      hydrocephalus). Despite normal initial cranial computed tomographic scan, diffuse
      swelling of the cerebellum with downward tonsillar herniation ensued. Diagnosis
      of hemophagocytic lymphohistiocytosis was difficult and delayed because of the
      relapsing course, and complete diagnostic criteria were not fulfilled at initial
      presentation. Central nervous system disease preceded the typical clinical
      picture of this disease; it dominated the clinical course and caused life
      threatening complications and sequelae. The patient improved after treatment,
      according to the hemophagocytic lymphohistiocytosis protocol (HLH-94) of the
      Histiocyte Society, with dexamethasone, etoposide, and cyclosporine and unrelated
      cord blood stem cell transplantation. A mutation in the perforin gene confirmed
      the diagnosis of familial hemophagocytic lymphohistiocytosis.

PMID- 15165641
TI  - Hemophagocytic syndrome associated with antiepileptic drug.
AB  - An 8-year-3-month-old male with right porencephaly and epilepsy was found to have
      skin rash 2 weeks after the beginning of treatment with lamotrigine. One month
      later he suffered from impaired liver function and pancytopenia in the presence
      of hypocellular bone marrow with hemophagocytosis. No evidence of infection was
      evident. Intravenous immunoglobulin and steroid were administered with
      discontinuation of lamotrigine; the hemogram and liver function profile improved
      dramatically. Hemophagocytic syndrome should be considered a possible cause of
      pancytopenia in patients taking new antiepileptic drugs such as lamotrigine.

PMID- 15165643
TI  - Sublingual lorazepam in the treatment of familial paroxysmal nonkinesigenic
      dyskinesia.
AB  - Familial paroxysmal nonkinesigenic dyskinesia (Mount and Reback syndrome) is
      characterized by episodes of dystonia and chorea, which are precipitated by
      fatigue, emotional stress, alcohol, or foods. We report two children from a large
      kindred with this condition who responded to sublingual lorazepam.

PMID- 15165644
TI  - Familial congenital facial palsy.
AB  - Congenital unilateral facial palsy has been described as a distinct entity, but
      there have been few reports of an isolated unilateral familial form, and no
      reports with supportive neuroimaging. We studied three males from three
      generations in the same family. Each had a left facial palsy, which was more
      pronounced with every successive generation. On the House grading scale, the
      proband, a 9-year-old male, manifested moderately severe facial nerve
      dysfunction. His 40-year-old father had mild to moderate dysfunction, and his 61
      year-old paternal grandfather manifested mild dysfunction. The proband and his
      father both had abnormal magnetic resonance imaging studies, with the proband's
      revealing enlargement and enhancement of the tympanic portion of the left facial
      nerve, and the father's demonstrating enhancement. Temporal bone computed
      tomography on the 9-year-old confirmed the enlarged left facial nerve. By
      electromyography/nerve conduction studies there was evidence of a chronic,
      incomplete, left facial palsy affecting both the father and his son, with
      substantially lowered compound muscle action potential amplitudes on the left.
      Congenital unilateral facial palsy spanning three generations with supportive
      neuroimaging and electromyography/nerve conduction studies has not been
      previously reported in the literature.

PMID- 15165646
TI  - Impact of a half-day multidisciplinary symptom control and palliative care
      outpatient clinic in a comprehensive cancer center on recommendations, symptom
      intensity, and patient satisfaction: a retrospective descriptive study.
AB  - To characterize a new, one-stop multidisciplinary palliative care (MD) clinic
      which offers standardized multidisciplinary assessment, specific care
      recommendations, patient and family education, and on-site counseling, we
      retrospectively compared the assessments of 138 consecutive patients with
      advanced cancer referred to the MD clinic and 77 patients referred to a
      traditional pain and symptom management (PSM) clinic. The two groups were similar
      in tumor type, demographics, and symptom distress. The MD clinic team
      (physicians; nurses; pharmacists; physical, speech, and occupational therapists;
      social workers; chaplains; nutritionists; psychiatric nurse practitioner)
      delivered 1,066 non-physician recommendations (median 4 per patient, range 0-37).
      The PSM clinic team made no non-physician recommendations, but referred 14
      patients to other medical specialists. In 80 (58%) MD-clinic patients with follow
      up 9 days (median) after assessment, significant improvement was observed in
      pain, nausea, depression, anxiety, sleep, dyspnea, and well-being, but not in
      fatigue, anorexia, or drowsiness. In 83 patients interviewed after the MD clinic,
      satisfaction was rated as excellent (5 out of 5) in 86-97% of seven areas.
      Assessment at an MD clinic results in a high number of patient care
      recommendations, improved symptoms, and high levels of patient satisfaction.

PMID- 15165647
TI  - Measuring the quality of structure and process in end-of-life care from the
      bereaved family perspective.
AB  - Measurement of the structure/process of care is the first step in improving end
      of-life care. The primary aim of this study was to psychometrically validate an
      instrument for directly measuring the bereaved family's perception of the
      necessity for improvement in structural/procedural aspects of palliative care.
      Different sets of questionnaires were sent to 800 and 425 families who lost
      family members at one of 70 certified palliative care units in Japan in the
      development and validation phases, respectively, and 281 families of the latter
      group in the follow-up phase. The participants were requested to fill out a newly
      developed Care Evaluation Scale (CES), along with outcome measures (the perceived
      experience and satisfaction levels) and potential covariates (the degree of
      expectation, the Center for Epidemiologic Studies Depression Scale, and the
      Social Desirability Scale). We obtained 485, 310, and 202 responses in the
      development, validation, and follow-up phases (response rates: 64%, 75%, and 72%,
      respectively). The 28-item CES had an overall Cronbach's coefficient alpha of
      0.98; the intra-class correlation coefficient in the test-retest examination was
      0.57. A confirmatory factor analysis revealed 10 subscales: physical care (by
      physicians, by nurses), psycho-existential care, help with decision-making (for
      patients, for family), environment, family burden, cost, availability, and
      coordination/consistency. The CES subscales were only moderately correlated with
      the perceived-experience and satisfaction levels of corresponding areas (r=0.36
      0.52 and 0.39-0.60, respectively). The CES score was not significantly associated
      with the degree of expectation, the changes of depression, or the Social
      Desirability Scale. The CES is a useful tool to measure the bereaved family's
      perception of the necessity for improvement in structural/procedural aspects of
      palliative care. The advantages of the CES are: 1) it specifically evaluates the
      structure and process of care, 2) it directly identifies needed improvements, 3)
      it is not affected by the degree of expectation, depression, or social
      desirability, and 4) it has satisfactory psychometric properties.

PMID- 15165648
TI  - What works for therapists conducting family meetings: treatment integrity in
      family-focused grief therapy during palliative care and bereavement.
AB  - The purpose of this study was to evaluate the treatment integrity of Family
      Focused Grief Therapy (FFGT), a preventive intervention designed for families at
      high risk of poor functioning during palliative care and bereavement. From the 81
      families participating in a randomized controlled trial (53 assigned to therapy),
      28 were randomly selected for this study of treatment fidelity using the FFGT
      integrity measure. A total of 109 family sessions were appraised. This
      represented a review of 62% of treated families, 38% of total therapy sessions,
      and 87% of the 15 participating therapists. Weighted mean percentage occurrences
      of therapist behaviors permitted trends in therapy application to be observed.
      Inter-rater reliability using the FFGT integrity measure was satisfactory, with
      88% overall agreement. Eighty-six percent of therapists adhered faithfully to
      core elements of the model. Therapist competence was evidenced by a strong
      therapeutic alliance (94%), affirmation of family strengths in over 90%, and
      focus on agreed themes in 76% of sessions. Therapists averaged 10 grief-related
      questions per session, 7 on communication-related issues during assessment, 7 on
      conflict late in therapy, and 4 on cohesiveness across the course of therapy.
      Consistent application of FFGT, with attention to its four key themes of family
      communication, cohesiveness, conflict resolution, and shared grief has been
      demonstrated. The model is generalizable when applied by family therapists.

PMID- 15165650
TI  - Consideration of hastening death among hospice patients and their families.
AB  - The purpose of this study was to describe hospice social workers' perceptions of
      cases where hospice patients or their family members expressed a desire to hasten
      the patient's death. Surveys were mailed to hospice social workers (n=212) in two
      Southeastern states. Response rate was 36%. Of the 73 respondents, 56.2% had a
      patient and 26.1% had a patient's family member express a desire to hasten the
      patient's death. Most patients had a cancer diagnosis (70.4%) and were
      predominantly male (66.6%), white (94.4%), and were married/had a partner
      (66.7%). Poor quality of life (28.3%) and concern for suffering (28.3%) were the
      most common reasons reported for the request to hasten death. These data suggest
      that the desire for hastened death is not uncommon among hospice patients. Social
      workers perceive these requests to be related primarily to unmet needs.

PMID- 15165651
TI  - Incidence and underlying etiologies of bronchial secretion in terminally ill
      cancer patients: a multicenter, prospective, observational study.
AB  - Although bronchial secretion is frequently observed in terminally ill cancer
      patients and can cause significant distress for both patients and family members,
      the pathophysiology is unclear. The primary aim of this study was to investigate
      the incidence and underlying etiologies of bronchial secretion. A multicenter,
      prospective, observational study was conducted on consecutive terminally ill
      patients with lung or abdominal malignancies. Primary physicians and nurses
      prospectively evaluated patients' symptoms. Of 310 patients enrolled, bronchial
      secretions were observed in 41% in the final 3 weeks, and oral/bronchial
      suctioning, with considerable distress, was required in 9%; bronchial secretions
      were severe in 4.5% of all patients. Multiple logistic regression analyses
      revealed that the determinants of the development of bronchial secretion were
      primary lung cancer, pneumonia, and dysphagia. There were no statistically
      significant effects of severity of peripheral edema and pleural effusion on
      development of bronchial secretions and requirement for oral/bronchial
      suctioning. Etiology-based classification of bronchial secretion is useful to
      identify the most suitable palliative treatments and to clarify treatment
      efficacy in each specific pathophysiology.

PMID- 15165649
TI  - The association between nocturnal hot flashes and sleep in breast cancer
      survivors.
AB  - This study examined the relationship between objectively measured nocturnal hot
      flashes and objectively measured sleep in breast cancer survivors with insomnia.
      Twenty-four women who had completed treatment for non-metastatic breast cancer
      participated. All were enrolled in a study of cognitive-behavioral treatment for
      chronic insomnia. Nocturnal hot flashes and sleep were measured by skin
      conductance and polysomnography, respectively. The 10-minute periods around hot
      flashes were found to have significantly more wake time, and more stage changes
      to lighter sleep, than other 10-minute periods during the night. Nights with hot
      flashes had a significantly higher percentage of wake time, a lower percentage of
      Stage 2 sleep, and a longer REM latency compared to nights without hot flashes.
      Overall, hot flashes were found to be associated with less efficient, more
      disrupted sleep. Nocturnal hot flashes, or their underlying mechanisms, should be
      considered as potential contributors to sleep disruption in women with breast
      cancer who report poor sleep.

PMID- 15165653
TI  - A community health center smoking-cessation intervention for pregnant and
      postpartum women.
AB  - OBJECTIVES: To evaluate the effect of a provider counseling and office systems
      intervention in obstetric, pediatric, and Special Supplemental Nutrition Program
      for Women, Infants and Children (WIC) clinics on smoking and relapse rates in
      pregnant and postpartum women. METHODS: Five community health centers were
      randomized to special intervention (SI) or usual care (UC). Subjects (n =601)
      were current smokers or had quit with pregnancy. Prenatal and postpartum
      interviews assessed smoking status and related factors. Data were collected
      between May 1997 and November 2000. RESULTS: There was a statistically
      significant difference in 30-day abstinence rates between SI (26%) and UC (12%)
      conditions at the end of pregnancy among women who had not quit spontaneously
      with pregnancy (odds ratio [OR]=2.57, p =0.05). This effect remained at 1 month
      postpartum but was lost at 3- and 6-month postpartum follow-ups. CONCLUSIONS:
      Brief interventions delivered by healthcare providers during routine prenatal
      care increased smoking abstinence during pregnancy among women who did not quit
      spontaneously. Interventions extended into postpartum care did not affect relapse
      and smoking rates postdelivery.

PMID- 15165652
TI  - Polyanalgesic Consensus Conference 2003: an update on the management of pain by
      intraspinal drug delivery-- report of an expert panel.
AB  - Intraspinal drug infusion using fully implantable pump and catheter systems is a
      safe and effective therapy for selected patients with chronic pain. The options
      for this approach are increasing, as drugs that are commercially available for
      systemic administration are adapted to this use and other drugs that are in
      development specifically for intraspinal administration become available. In 2000
      a Polyanalgesic Consensus Conference was organized to evaluate the existing
      literature and develop guidelines for drug selection. The major outcome of this
      effort, an algorithm for drug selection, was based on the best available evidence
      at the time. Rapid changes have occurred in the science and practice of
      intraspinal infusion and a Polyanalgesic Consensus Conference 2003 was organized
      to pursue the following goals: 1) to review the literature on intraspinal drug
      infusion since 1999, 2) to revise the 2000 drug-selection algorithm, 3) to
      develop guidelines for optimizing drug dosage and concentration, 4) to create a
      process for documenting minimum evidence supporting the use of a drug for
      intraspinal infusion, and 5) to clarify issues pertaining to compounding of
      drugs. Based on the best available evidence and expert opinion, consensus
      recommendations were developed in all these areas. The panel's conclusions may
      provide a foundation for clinical practice and a rational basis for new research.

PMID- 15165654
TI  - Training support persons to help smokers quit: a pilot study.
AB  - BACKGROUND: Evaluate the feasibility, acceptability, and potential efficacy of a
      skills-training intervention for adults interested in helping someone to stop
      smoking (i.e., support persons). METHODS: Sixty adult support persons (77%
      female) were directly recruited from the community and randomly assigned to this
      intervention (manual plus five weekly group-based sessions) or a control
      condition (one-page leaflet). All intervention and outcome assessments occurred
      through the support persons. Assessments occurred at weeks 0 (baseline), 6 (end
      of treatment), 12, and 24. The study was conducted from 1998 to 2001; data
      collection occurred from 1999 to 2000. Outcomes were ratings of treatment
      acceptability, recruitment and retention rates, supportive behaviors provided to
      the smoker, and smoking behavior change in the smoker as reported by the support
      person. RESULTS: Support persons were recruited in a timely manner and study
      retention rates were high. Support persons in skills training showed significant
      increases in their supportive behavior scores compared with control subjects at
      weeks 6 and 12. Although not statistically significant, the skills-training
      intervention was associated with more quit attempts, greater improvement in stage
      of change, and higher 7-day point prevalence abstinence rates in the smokers than
      the control condition. CONCLUSIONS: A skills training intervention for support
      persons is feasible and acceptable. Further studies are needed to test the
      efficacy of this approach for smoking cessation.

PMID- 15165655
TI  - Smoking-cessation interventions by type of provider: a meta-analysis.
AB  - OBJECTIVE: To synthesize the evidence on the effectiveness of smoking-cessation
      interventions by type of provider. METHODS: A random effects meta-regression was
      estimated to examine the effect of provider and whether the intervention
      contained nicotine replacement therapy (NRT), on the intervention's relative risk
      of quitting as compared to placebo or usual care from studies published in
      databases from inception to 2000. Thirty additional studies not included in the
      previous 1996 and 2000 U.S. Public Health Service clinical practice guidelines
      were used to provide the most comprehensive analysis to date of the comparative
      effectiveness of different types of providers in interventions for smoking
      cessation that have been published. RESULTS: The effectiveness without NRT
      follows: psychologist (1.94, 95% confidence interval [CI]: 1.04-3.62); physician
      (1.87, CI=1.42-2.45); counselor (1.82, CI=0.84-3.96); nurse (1.76, CI=1.21-2.57);
      unknown (1.27, CI=0.57-2.82); other (1.18, CI=0.67-2.10); and self-help (1.28,
      CI=0.89-1.82). Effectiveness of most providers increased by almost twofold with
      the use of NRT. CONCLUSIONS: Smoking-cessation interventions without NRT
      delivered by psychologists, physicians, or nurses are all effective. NRT
      increases the effectiveness of most providers.

PMID- 15165656
TI  - Attempting to lose weight: specific practices among U.S. adults.
AB  - BACKGROUND: Americans spend over $33 billion annually on weight-loss products and
      services. Although weight-control methods are of considerable public health
      interest, few national data on weight-loss practices are available. This paper
      examines the prevalence of specific weight-loss practices among U.S. adults
      trying to lose weight. METHODS: Data from the 1998 National Health Interview
      Survey, which was conducted through face-to-face interviews of a nationally
      representative sample of U.S. adults (n =32,440), were analyzed in 2003. RESULTS:
      Twenty-four percent of men and 38% of women were trying to lose weight.
      Attempting weight loss was less common among normal weight (body mass index
      [BMI]<25 kg/m(2)) people (6% men, 24% women) than overweight (BMI>/=25 to 30
      kg/m(2)) people (28%, 49%) or obese (BMI>/=30 kg/m(2)) people (50%, 58%). Among
      those trying to lose weight, the most common strategies were eating fewer
      calories (58% men, 63% women); eating less fat (49%, 56%); and exercising more
      (54%, 52%). Less frequent strategies were skipping meals (11% men, 9% women);
      eating food supplements (5%, 6%); joining a weight-loss program (3%, 5%); taking
      diet pills (2%, 3%); taking water pills or diuretics (1%, 2%); or fasting for
      >/=24 hours (0.6%, 0.7%). Only one third of all those trying to lose weight
      reported eating fewer calories and exercising more. CONCLUSIONS: Increased
      efforts are needed among all those trying to lose weight to promote effective
      strategies for weight loss, including the use of calorie reduction and increased
      physical activity.

PMID- 15165657
TI  - Physical activity decreases cardiovascular disease risk in women: review and meta
      analysis.
AB  - OBJECTIVE: To review and quantify the dose-response relationship of physical
      activity (PA) in initially healthy women on cardiovascular disease (CVD)
      outcomes, especially coronary heart disease (CHD) and stroke, and to assess the
      minimum amount of PA to reduce CVD risk. DATA SOURCES: Studies on PA and CVD were
      searched in MEDLINE (January 1966-March 2003) with additional manual searches.
      DATA SELECTION: Studies were included if they (1) provided data on women; (2)
      assessed PA (exposure) as either a continuous variable or a categorical variable
      with three or more levels, and CVD (outcome); and (3) provided information on
      relative risks (RRs) and 95% confidence intervals. DATA EXTRACTION: Studies were
      reviewed, abstracted, and rated for quality by each author. DATA SYNTHESIS:
      Thirty articles met the inclusion criteria. When studies were combined according
      to relative PA levels, the RRs showed a dose-response relationship for CHD (RR=1
      [reference], 0.78, 0.53, 0.61, respectively; p for trend was <0.0001 for studies
      with four PA levels, n =5); for stroke (RR=1 [reference], 0.73, 0.68, p for trend
      was <0.0001 for studies with three PA levels, n =7); and for overall CVD (RR=1
      [reference], 0.82, 0.78, p for trend was <0.0001 for studies with three PA
      levels, n =6). When studies were combined by absolute walking amount, even 1
      hour/week walk was associated with reduced risk of CVD outcome. CONCLUSIONS:
      Physical activity was associated with reduced risk of CVD among women in a dose
      response fashion. Inactive women would benefit by even slightly increasing their
      PA (e.g., walking 1 hour per week or possibly less) and even more from additional
      PA.

PMID- 15165658
TI  - Physical activity participation among persons with disabilities: barriers and
      facilitators.
AB  - BACKGROUND: The purpose of this study was to identify various barriers and
      facilitators associated with participation in fitness and recreation
      programs/facilities among persons with disabilities. METHODS: Focus groups were
      conducted in ten regions across the United States in 2001 to 2002 with four types
      of participants: (1) consumers with disabilities, (2) architects, (3) fitness and
      recreation professionals, and (4) city planners and park district managers.
      Sessions were tape-recorded and content analyzed; focus group facilitators took
      notes of identified barriers and facilitators to access. RESULTS: Content
      analysis of tape recordings revealed 178 barriers and 130 facilitators. The
      following themes were identified: (1) barriers and facilitators related to the
      built and natural environment; (2) economic issues; (3) emotional and
      psychological barriers; (4) equipment barriers; (5) barriers related to the use
      and interpretation of guidelines, codes, regulations, and laws; (6) information
      related barriers; (7) professional knowledge, education, and training issues; (8)
      perceptions and attitudes of persons who are not disabled, including
      professionals; (9) policies and procedures both at the facility and community
      level; and (10) availability of resources. CONCLUSIONS: The degree of
      participation in physical activity among people with disabilities is affected by
      a multifactorial set of barriers and facilitators that are unique to this
      population. Future research should utilize this information to develop
      intervention strategies that have a greater likelihood of success.

PMID- 15165659
TI  - Visit satisfaction and tailored health behavior communications in primary care.
AB  - BACKGROUND: Although studies suggest that computer-tailored health communications
      can help patients improve health behaviors, their effect on patient satisfaction,
      when used in healthcare settings, has yet to be examined. METHODS: A stand-alone
      computer application was developed to provide tailored, printed feedback for
      patients and physicians about two of the most common adverse health behaviors
      seen in primary care: smoking and physical inactivity. Ten primary care providers
      and 150 of their patients were recruited to use the program in the office before
      their visit. After the visit, patients completed a self-report survey that
      addressed demographics, computer use history, satisfaction with the visit, and
      the extent to which the physician addressed the reports during the visit. All
      data presented were collected between October 2001 and February 2002. RESULTS:
      Most patients were female (67.6%), approximately half (46.0%) were seen for a
      routine exam, most (63.3%) had at least one chronic illness, and fewer than one
      third (31.3%) had ever used the Internet or e-mail. Most (81.1%) patients
      reported that the program was easy to use, but fewer than half of the doctors
      looked at the report in front of the patient (49.2%) or discussed the report with
      the patient (44.3%). Multivariate modeling showed that visit satisfaction was
      significantly greater among those whose doctor examined the report. This effect
      of the doctor examining the report on satisfaction was even greater for those who
      reported a chronic illness. CONCLUSIONS: Physicians who incorporate computer
      tailored messaging programs into the primary care setting, but who do not address
      the feedback reports that they create may contribute to patients being less
      satisfied with their care.

PMID- 15165660
TI  - Mailings timed to patients' appointments: a controlled trial of fecal occult
      blood test cards.
AB  - BACKGROUND: Fecal occult blood testing (FOBT) programs cost-effectively reduce
      colon cancer mortality. To improve the rate of colon cancer screening with FOBT,
      we tested the effect of mailing FOBT cards timed to appointments on the rates of
      completion of FOBT. DESIGN: Controlled trial. SETTING/PARTICIPANTS: A total of
      119 patients with primary care appointments scheduled in May or June 2000 for an
      urban, public hospital clinic that serves predominantly low-income, African
      Americans with chronic diseases. The patients in the study were selected by
      linking a quality improvement registry, the appointment system database, and an
      FOBT database to generate a list of clinic patients who had not completed an FOBT
      in the preceding year. INTERVENTION: Subjects were assigned to either a system of
      mailing FOBT cards and reminders 2 weeks prior to a scheduled appointment or
      usual care. MAIN OUTCOME MEASURES: The primary outcomes were the rate of
      screening at the index appointment and during the year beginning with the date of
      the index appointment. RESULTS: The rate of return of the FOBT cards during the
      year beginning with the index appointment was 40.7% for the intervention group
      compared to 5% for the usual care group (odds ratio [OR]=13.0, p <0.001). The
      difference was accounted for largely by increases in screening at the index
      appointment (35.6% compared to 3.3%, OR=16.0, p <0.001). CONCLUSIONS: Using
      computer databases to generate a list of patients due for FOBT and then mailing
      FOBT cards timed to a scheduled appointment significantly increased the rate of
      colon cancer screening. This may be an efficient approach to increasing colon
      cancer screening with FOBT.

PMID- 15165661
TI  - Modifiable predictors of bone loss in older men: a prospective study.
AB  - BACKGROUND: The determinants of change in bone mineral density (BMD) have been
      well characterized in women but not in men. This prospective study describes the
      patterns of BMD change at the hip and spine, incidence of osteoporosis, and
      modifiable predictors of bone loss in 507 ambulatory community-dwelling men aged
      45 to 92 years. METHODS: Bone mineral density was assessed at the hip and lumbar
      spine by dual-energy x-ray absorptiometry (DEXA) between 1988 and 1992 and again
      4 years later. BMD change was examined both as a continuous and a dichotomous
      (BMD loss vs no change/gain) variable. Incidence of osteoporosis was evaluated
      based on t -scores. Data were analyzed in 2002. RESULTS: Annual BMD loss averaged
      0.47% at the total hip and 0.34% at the femoral neck with an annual average of
      0.22% gain at the spine. The rate of BMD loss at the hip and incidence of
      osteoporosis increased significantly with age. The main predictors of BMD loss
      were age >/=75 years, baseline BMI <24 kg/m(2), 4-year weight loss of >/=5%,
      current smoking, and physical inactivity. Moderate alcohol consumption showed
      some bone-sparing effect. Diuretic and calcium supplement use were not associated
      with bone loss. CONCLUSIONS: Relatively healthy community-dwelling men lose bone
      with age, and men aged >/=75 years are particularly vulnerable. Potentially
      modifiable characteristics such as low body mass, weight loss, smoking, and
      physical inactivity were important predictors of bone loss and should be
      considered for the prevention of osteoporosis in men.

PMID- 15165662
TI  - After more than 10 years of Gulf War veteran medical evaluations, what have we
      learned?
AB  - Since the 1991 Gulf War, more than 10 years and 1 billion dollars of health
      evaluations and research have been invested in understanding illnesses among Gulf
      War veterans. We examined the extensive published healthcare utilization data in
      an effort to summarize what has been learned. Using multiple search techniques,
      data as of June 2003 from four different national Gulf War health registries and
      numerous hospitalization and ambulatory care reports were reviewed. Thus far,
      published reports have not revealed a unique Gulf War syndrome nor identified
      specific exposures that might explain postwar morbidity. Instead, they have
      demonstrated that Gulf War veterans have had an increase in multi-symptom
      condition, injury, and mental health diagnoses. While these diagnoses are similar
      to those experienced by other comparable military populations, their explanation
      is not fully understood. New strategies to identify risk factors for, and to
      reduce, such postdeployment conditions are summarized.

PMID- 15165663
TI  - Comparison of small-area analysis techniques for estimating county-level
      outcomes.
AB  - BACKGROUND: Since many health data are unavailable at the county level,
      policymakers sometimes rely on state-level datasets to understand the health
      needs of their communities. This can be accomplished using small-area estimation
      techniques. However, it is unknown which small- area technique produces the most
      valid and precise results. METHODS: The reliability and accuracy of three methods
      used in small-area analyses were examined, including the synthetic method,
      spatial smoothing, and regression. To do this, severe work disability measures
      were first validated by comparing the 2000 Behavioral Risk Factor Surveillance
      System (BRFSS) and Census 2000 measures (used as the gold standard). The three
      small-area analysis methods were then applied to 2000 BRFSS data to examine how
      well each technique predicted county-level disability prevalence. RESULTS: The
      regression method produces the most valid and precise estimates of county-level
      disability prevalence over a large number of counties when a single year of data
      is used. CONCLUSIONS: Local health departments and policymakers who need to track
      trends in behavioral risk factors and health status within their counties should
      utilize the regression method unless their county is large enough for direct
      estimation of the outcome of interest.

PMID- 15165664
TI  - In response to the 2003, vol. 25, no. 3 article entitled: subject: the
      iatroepidemic.

PMID- 15165666
TI  - Cerebrospinal fluid and serum vascular endothelial growth factor and nitric oxide
      levels in newborns with hypoxic ischemic encephalopathy.
AB  - Excitatory amino acids, cytokines and nitric oxide (NO) have been studied in the
      etiology and pathogenesis of hypoxic ischemic encephalopathy (HIE) of the
      newborn. Vascular endothelial growth factor (VEGF) is a known mediator of
      angiogenesis and has been shown to induce vascular proliferation and permeability
      via NO-mediated mechanism during hypoxia. The objective of this study was to
      investigate the cerebrospinal fluid and serum VEGF and NO levels in different
      stages of HIE and the correlation between the two mediators. Cerebrospinal fluid
      (CSF) and serum samples of 19 newborns with HIE and 13 controls were obtained
      within the first 24 h of life and kept at -70 degrees C until the time of
      measurement. NO levels were determined by Sievers NOA by chemiluminescence method
      and VEGF levels were measured by the enzyme-linked immunosorbent assay double
      sandwich method. The NO levels in CSF were higher than the control and mild HIE
      group in newborns with moderate to severe HIE, and VEGF levels in CSF were higher
      in the mild HIE group compared to controls but similar in the moderate to severe
      HIE group compared to mild HIE and control patients. There was no difference
      between groups with regard to serum NO or VEGF levels, and no correlation was
      observed between NO and VEGF levels both in CSF and serum samples. Depending on
      the severity of the hypoxic insult the stimulus for NO production by VEGF may
      have variable effects on endothelial cells which may give rise to the current
      results.

PMID- 15165667
TI  - A novel missense mutation of the GTP cyclohydrolase I gene in a Korean family
      with hereditary progressive dystonia/dopa-responsive dystonia.
AB  - Hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive
      dystonia (HPD/DRD) shows the considerable heterogeneity of clinical phenotypic
      expression and a dramatic sustained response to levodopa. The autosomal dominant
      HPD/DRD is caused by mutations in the gene coding GTP cyclohydrolase I (GCH I),
      the enzyme that catalyzes the first step in the biosynthesis of
      tetrahydrobiopterin. Previous studies suggested that normal [18F]Dopa positron
      emission tomography or [123I]beta-CIT single-photon emission computed tomography
      (SPECT) imaging, indicating intact structural integrity of nigrostriatal neurons,
      may be useful for differentiating HPD/DRD from clinically similar conditions such
      as juvenile Parkinson's disease with dystonia that have a considerably poorer
      prognosis. We here report a Korean family affected with HPD/DRD due to a novel
      missense mutation of the GCH I gene (T-->G mutation in exon 2), Met 137 Arg,
      which may change the conformation of the binding site of GCH I. The clinical
      features are considerably variable within the family. We documented normal
      striatal uptake of [123I]IPT, a dopamine transporter ligand with fast washout
      kinetics, in our patients by using SPECT. This method can be helpful in
      diagnosing HPD/DRD in uncertain cases.

PMID- 15165668
TI  - Serum neurotrophin concentrations in autism and mental retardation: a pilot
      study.
AB  - To evaluate the availability of the serum neurotrophins for the diagnosis of the
      patients with neurodevelopmental disorder, we measured the serum concentration of
      brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in the
      patients diagnosed with autism (n=18) and mental retardation (n=20), or healthy
      controls (n=16), using enzyme-linked immunosorbent assay. There tended to be a
      higher concentration of serum BDNF found in the autistic group ( P <0.05 by
      analysis of variance (ANOVA)) and the mental retardation group ( P <0.001 by
      ANOVA) compared to the control group. Serum NT-4 concentration tended to be
      increased in the mental retardation group (P <0.05 by ANOVA). We conclude that
      measuring the serum concentration of two neurotrophins, BDNF and NT-4, might be
      helpful to diagnose or classify disorders such as autism or mental retardation.

PMID- 15165669
TI  - An evaluation of serious neurological disorders following immunization: a
      comparison of whole-cell pertussis and acellular pertussis vaccines.
AB  - Serious neurological disorders reported following whole-cell pertussis in
      comparison to acellular pertussis vaccines were evaluated. The Vaccine Adverse
      Events Reporting System (VAERS) was analyzed for Emergency Department (ED)
      visits, life-threatening reactions, hospitalizations, disabilities, deaths,
      seizures, infantile spasms, encephalitis/encephalopathy, autism, Sudden Infant
      Death Syndrome (SIDS) and speech disorders reported with an initial onset of
      symptoms within 3 days following whole-cell pertussis and acellular pertussis
      vaccines among those residing in the US from 1997 to 1999. Controls were employed
      to evaluate potential biases in VAERS. Evaluations as to whether whole-cell and
      acellular vaccines were administered to populations of similar age and sex were
      undertaken because these factors might influence the study's results. Statistical
      increases were observed for all events examined following whole-cell pertussis
      vaccination in comparison to acellular pertussis vaccination, excepting
      cerebellar ataxia. Reporting biases were minimal in VAERS, and whole-cell and
      acellular pertussis vaccines were administered to populations of similar age and
      sex. Biologic mechanisms for the increased reactogenicity of whole-cell pertussis
      vaccines may stem from the fact that whole-cell pertussis vaccines contain 3,000
      different proteins, whereas DTaP contains two to five proteins. Whole-cell
      pertussis vaccine contains known neurotoxins including: endotoxin, pertussis
      toxin and adenylate cyclase. Our results, and conclusions by the US Institute of
      Medicine, suggest an association between serious neurological disorders and whole
      cell pertussis immunization. In light of the presence of a safer and at least
      equally efficacious acellular pertussis vaccine alternative, the Japanese and US
      switch to using acellular pertussis vaccine seems well justified. Other countries
      using whole-cell pertussis-containing vaccines should consider following suite in
      the near future.

PMID- 15165670
TI  - The metaphor and sarcasm scenario test: a new instrument to help differentiate
      high functioning pervasive developmental disorder from attention
      deficit/hyperactivity disorder.
AB  - It is sometimes difficult to discriminate high functioning pervasive
      developmental disorders (HFPDD) from attention deficit/hyperactivity disorders
      (AD/HD) in young children because of the behavioral similarities between the two.
      For adequate diagnosis, understanding fundamental differences in their social
      cognitive abilities might become significant. In order to detect the differences
      in social cognitive abilities between AD/HD and HFPDD, a new test, the Metaphor
      and Sarcasm Scenario Test (MSST) was developed. One hundred and ninety-nine
      normal school children (the control group), 29 AD/HD children and 54 HFPDD
      children were involved. The results showed that the inability to understand a
      sarcastic situation was specific to children with HFPDD, both children with AD/HD
      and HFPDD could not equally understand metaphor. The correlation between the
      comprehension of sarcasm and success in the theory of mind task was remarkably
      high but not for comprehension of metaphor. In conclusion, the MSST has the
      potential to discriminate HFPDD from AD/HD in young children.

PMID- 15165671
TI  - Brain macrophages and microglia in human fetal hydrocephalus.
AB  - Whereas several studies have addressed the activation of microglia (the resident
      mononuclear phagocytes of the brain) and macrophages within the nervous system in
      experimental animal models of congenital and induced hydrocephalus, little is
      known of their state of activation or regional distribution in human fetal
      hydrocephalus. This investigation aimed to address such questions. Ten human
      fetal cases [20-36 gestational weeks (GW) at postmortem] previously diagnosed
      with hydrocephalus on ultrasound examination in utero, and 10 non-hydrocephalic
      controls (22-38 GW at postmortem) were assessed immufcnohistochemically with
      antibodies directed against MHC class II and CD68 antigens, and lectin
      histochemistry with Lycopersicon esculentum (tomato lectin). Adjacent sections
      were also immunoreacted with an antiserum to laminin to detect cerebral blood
      vessels. Eight out of the 10 hydrocephalus cases showed numerous CD68 and tomato
      lectin-positive macrophages located at focal regions along the ependymal lining
      of the lateral ventricles (particularly within the occipital horn). However, only
      five of these cases demonstrated MHC class II positive macrophages associated
      with the ventricular lining. Microglial reactivity within periventricular regions
      could also be identified using the lectin in four cases, two of which were also
      immunoreactive with CD68 (but not with MHC class II). By comparison, in control
      cases five out of 10 fetal brains (aged between 20 and 24 GW) showed few or no
      ependymal or supraependymal macrophages. One case at 28 GW, and cases at 32 and
      38 GW (two of which were diagnosed with intrauterine hypoxic-ischemia) did,
      however, show some MHC class II (CD68 negative) cells located at the ependymal
      surface. Nevertheless, these were not as numerous or intensely immunoreactive as
      in the hydrocephalus cases. Microglia interspersed throughout the intermediate
      zone and circumscribing the basal ganglia were within normal confines in all
      cases examined. Hydrocephalic cases additionally showed focal regions of
      hypovascularization or alterations in the structure and orientation of
      capillaries within periventricular areas, compared to controls. The macrophage
      response detected at the ependymal lining of the ventricles and within the
      periventricular area in hydrocephalus may be related both to the severity of
      hydrocephalus and the age of the fetus.

PMID- 15165672
TI  - Cytoarchitectural organization of the parabrachial/Kolliker-Fuse complex in man.
AB  - While the parabrachial/Kolliker-Fuse complex has been described in a variety of
      animal species it has not been characterized in human brainstem. In the present
      study we investigated fetal and infant brainstems, focusing particularly on the
      dorsolateral part of the pontine tegmentum, with the aim of defining the precise
      cytoarchitecture of the medial parabrachial, lateral parabrachial, and Kolliker
      Fuse nuclei in man, and analyzing the developmental stages of this complex. In
      serial sections of 28 human brainstems of subjects aged between 32 gestational
      weeks and 1 year we made a morphologic and morphometric analysis of the shape and
      size of the parabrachial/Kolliker-Fuse complex. We observed a homogeneous
      morphology in all cases, which enabled us to define the structure of the three
      nuclei. The features of the parabrachial nuclei are largely consistent with those
      reported in experimental studies. However, the Kolliker-Fuse nucleus appears to
      be more developed in human beings than in other animal species, showing a greater
      extension and a more complex structure. The neuronal maturation of these nuclei
      was seen to occur between the 35th and the 36th gestational weeks.

PMID- 15165673
TI  - A clinical study of febrile myoclonus in children.
AB  - Fever is sometimes associated with chill, myoclonus, delirium and convulsion. We
      previously reported EEG findings of febrile delirium, when we found that 18% of
      patients showed febrile myoclonus simultaneously with febrile delirium. The
      purpose of this study is to clarify the clinical features of febrile myoclonus
      and to investigate the relation to febrile convulsion. Myoclonic episodes were
      studied in 11 patients, aged 8 months to 11 years. EEG was recorded in eight
      patients. In the past history, febrile convulsion was noted in two patients and
      one of them also had febrile delirium. The age range of patients with febrile
      myoclonus was similar to those developing febrile convulsion except for one case.
      The duration of febrile myoclonus was usually from several to 30 min, but was
      longer than 2 h in four patients. Seventy-three percent of patients showed fear,
      surprise and shouting. EEG was abnormal in four patients and spike components
      were found in two patients. Myoclonic jerks were seen during the EEG recording in
      two patients and EEG findings were not concordant with epileptic myoclonic
      attack. Ten patients were followed for 1-2 years, and none had afebrile seizures.
      Febrile myoclonus is a benign symptom associated with fever. Mood change, fear or
      surprise and shouting with myoclonic jerks may suggest action of cytokine on the
      hypothalamus induced by infection. Febrile myoclonus, delirium and convulsion
      were seen in one patient in his first 3 years of life. These three symptoms seem
      to appear in children depending on their predisposition.

PMID- 15165675
TI  - Laryngeal dystonia in a case of severe motor and intellectual disabilities due to
      Japanese encephalitis sequelae.
AB  - Laryngeal dystonia is characterized by stridor due to vocal cord dystonia and is
      observed in extrapyramidal disorders. Recently, botulinum toxin injection has
      been used as a primary therapy. Generally, severe motor and intellectual
      disabilities (SMID) are frequently complicated by various types of respiratory
      disorders. We report a SMID case with Japanese encephalitis sequelae showing
      repeated vocal cord abductor disturbance due to laryngeal dystonia, in addition
      to generalized dystonia, in whom MRI revealed basal ganglia lesions. Tracheostomy
      was effective for the case, and we believe that botulinum toxin injection may be
      inappropriate in SMID, both ethically and technically. Also, laryngeal dystonia
      should be considered as a cause of respiratory disorders in SMID.

PMID- 15165674
TI  - Etiological heterogeneity of familial periventricular heterotopia and
      hydrocephalus.
AB  - Periventricular heterotopia (PH) represents a neuronal migration disorder that
      results in gray matter nodules along the lateral ventricles beneath an otherwise
      normal appearing cortex. While prior reports have shown that mutations in the
      filamin A (FLNA) gene can cause X-linked dominant PH, an increasing number of
      studies suggest the existence of additional PH syndromes. Further classification
      of these cortical malformation syndromes associated with PH allows for
      determination of the causal genes. Here we report three familial cases of PH with
      hydrocephalus. One pedigree has a known FLNA mutation with hydrocephalus
      occurring in the setting of valproic acid exposure. Another pedigree demonstrated
      possible linkage to the Xq28 locus including FLNA, although uncharacteristically
      a male was affected and sequencing of the FLNA gene in this individual revealed
      no mutation. However, in the third family with an autosomal mode of inheritance,
      microsatellite analysis ruled out linkage with the FLNA gene. Routine karyotyping
      and fluorescent in situ hybridization using BAC probes localized to FLNA also
      showed no evidence of genomic rearrangement. Western blot analysis of one of the
      affected individuals demonstrated normal expression of the FLNA protein. Lastly,
      sequencing of greater than 95% of the FLNA gene in an affected member failed to
      demonstrate a mutation. In conclusion, these findings demonstrate the etiological
      heterogeneity of PH with hydrocephalus. Furthermore, there likely exists an
      autosomal PH gene, distinct from the previously described X-linked and autosomal
      recessive forms. Affected individuals have severe developmental delay and may
      have radiographic findings of hydrocephalus.

PMID- 15165676
TI  - Thelarche variant in a girl with Angelman syndrome.
AB  - A case of Angelman syndrome (AS) with thelarche variant in a 4.5-year-old girl is
      presented. Clinical suspicion of AS was raised at the age of 15 months when she
      presented with mental retardation and epilepsy, absence of speech, ataxic gait
      with jerky movements, hyperactivity and paroxysmal episodes of laughter.
      Moreover, she had facial dysmorphic features such as microbrachycephaly, mid
      facial hypoplasia, macrostomia and prominent mandible. Dinucleotide repeat
      polymorphism (DNRP) analysis, identified absence of maternal alleles at D15S543,
      D15S113 and GABRB3 loci, findings consistent with AS. Studies on CYP19 locus
      (outside the 15q11-13 region) revealed the presence of two different alleles,
      thus excluding the possibility of paternal isodisomy of chromosome 15 in this
      patient. Breast development at the age of 4.5 years, accompanied by accelerated
      growth velocity and bone age suggested the diagnosis of variant thelarche. This
      is the second case of AS with sexual precocity reported and whether this
      combination is a coincidence or not remains to be clarified.

PMID- 15165677
TI  - Hematological abnormalities in a patient with a 22q11.2 deletion.
AB  - We report a case of a 28-year-old man carrying a 22q11.2 deletion and presenting
      with giant platelets, thrombocytopenia and leukocyte inclusion bodies. In our
      patient, platelet glycoproteins were normally expressed on membranes and platelet
      function was preserved. The May-Hegglin anomaly or Sebastian syndrome associated
      with the 22q11.2 deletion was suggested. Atypical features also included the lack
      of any cardiovascular defect, T cell deficit or palate anomaly, generally common
      with this deletion.

PMID- 15165678
TI  - Trial of intraventricular ribavirin therapy for subacute sclerosing
      panencephalitis in Japan.

PMID- 15165680
TI  - [50th French Congress of Internal Medicine. Bruges, Belgium, 7-11 June 2004.
      Proceedings and abstracts].

PMID- 15165681
TI  - [Mechanisms of formation of atheroma plaque].

PMID- 15165683
TI  - Anti-phospholipid syndrome from a systemic disease toward the infectious
      etiology.

PMID- 15165682
TI  - [Inflammation markers and vascular risk].

PMID- 15165684
TI  - [Antiphospholipids, systemic lupus, and atherosclerosis: clinical features].

PMID- 15165686
TI  - [Anti-synthetases syndrome].

PMID- 15165685
TI  - The molecular pathophysiology in inflammatory myopathies.

PMID- 15165687
TI  - [Inclusion myositis].

PMID- 15165689
TI  - [Long-term clinical course of idiopathic inflammatory myopathies].

PMID- 15165688
TI  - [Treatment of polymyositis and dermatomyositis].

PMID- 15165690
TI  - Biomarkers for Alzheimer's disease. Which way to go?

PMID- 15165691
TI  - Spatial and temporal relationships between plaques and tangles in Alzheimer
      pathology.
AB  - One histological hallmark in Alzheimer's disease is the tangle. The other is the
      plaque. A widely discussed hypothesis is the "amyloid cascade" assuming that
      tangle formation is a direct consequence of amyloid plaque formation. The aim of
      this study was to examine plaques and tangles in a highly defined neuronal
      circuitry in order to determine their detailed spatial and temporal
      relationships. We investigated serial sections of the whole hippocampal formation
      of brains with early Braak-stages (0-III) for tangles only, i.e. one case at
      stage 0, six at stage I, six at stage II, and nine at stage III. Most cases
      displayed both plaques and tangles. Four cases of stages 0 and I, three cases
      with stage II, and even one with stage III, however, did not display plaques. In
      turn, no plaque was found in the absence of tangles. The spatial relationship
      indicates that plaques lay in the terminal fields of tangle-bearing neurons. Our
      analysis suggests that tangles either antecede plaques or--less likely--are
      independently formed.

PMID- 15165692
TI  - Alzheimer's disease: intraneuronal alterations precede insoluble amyloid-beta
      formation.

PMID- 15165693
TI  - The uncertain anatomy of Alzheimer's disease.

PMID- 15165694
TI  - So what if tangles precede plaques?

PMID- 15165695
TI  - Alzheimer's disease--a sum greater than its parts?

PMID- 15165696
TI  - Looking for the link between plaques and tangles.

PMID- 15165699
TI  - Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer
      Disease: from risk factors to disease modulators.
AB  - Increasing biological and clinical findings argue for a link between brain
      cholesterol turnover and Alzheimer Disease (AD), high cerebral levels of the
      former increasing Abeta load. Cerebral cholesterol elimination involves two
      mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase
      (CYP46). The aim of this study was to evaluate an intronic variation in CYP46
      (intron 2, T --> C ) along with ApoE genotype as risk factors for AD and to
      establish the correlation between CYP46/ApoE polymorphism and disease
      progression. One-hundred and fifty-seven AD patients, who had been followed
      periodically through 1-year follow-up after enrollment, and 134 age- and gender
      matched controls entered the study. The distribution of CYP46 genotypes was
      significantly different in AD compared to controls (P<0.004), being CYP*C allele
      higher in AD patients ( P<0.002). ApoE 4 genotype was more frequent in AD (41.4%)
      than in controls (15.9%, P<0.0001). The odds ratio (OR) for AD risk in CYP46*C
      carriers was 2.8, and in ApoE epsilon4 carriers was 4.05; the OR for having both
      CYP46*C and ApoE epsilon4 was 17.75, demonstrating the their synergic effect on
      AD risk. In AD patients, CYP46*C along with ApoE epsilon4 genotype were
      associated with a higher cognitive decline at 1-year follow-up (P<0.02). These
      findings provide direct evidence that CYP46 and ApoE polymorphisms synergically
      increase the risk for AD development, and influence on the rate of cognitive
      decline.

PMID- 15165697
TI  - Tangles precede plaques but don't cause them.

PMID- 15165700
TI  - Increased caveolin-1 expression in Alzheimer's disease brain.
AB  - Increasing evidence suggests that cholesterol plays a central role in the
      pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding
      membrane protein involved in cellular cholesterol transport. We investigated the
      changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and
      aged-matched control subjects. Our results demonstrate that caveolin protein
      levels in the hippocampus and caveolin mRNA in the frontal cortex are up
      regulated in AD by approximately two-fold, compared to control brains. These
      results suggest a relationship between caveolin-1 expression levels and a
      dysregulation of cholesterol homeostasis at the plasma membrane of brain cells.
      In support of this hypothesis, a significant increase in caveolin protein levels
      has also been observed in hippocampal tissue from ApoE-deficient (knockout) and
      aged wild-type mice; two situations associated with modifications of transbilayer
      distribution of cholesterol in brain synaptic plasma membranes. These results
      indicate that caveolin over-expression is linked to alterations of cholesterol
      distribution in the plasma membrane of brain cells and are consistent with the
      notion of a deterioration of cholesterol homeostasis in AD.

PMID- 15165701
TI  - The influence of sex on limbic volume and perfusion in AD.
AB  - The goal of the current study was to determine whether Alzheimer's disease (AD)
      pathology affects the limbic system of men and women differently as measured by
      in vivo neuroimaging. Magnetic resonance imaging (MRI) and coregistered single
      photon emission computed tomography (SPECT) were used to examine the limbic
      system in 20 men and 20 women with probable AD compared to 40 age- and education
      matched normal controls (20 men, 20 women). Limbic volumes and relative perfusion
      values were obtained from the MR images and coregistered SPECT scans,
      respectively. No significant differences were found between sexes in limbic
      volumes or relative perfusion values in the normal controls. Many limbic regions
      were significantly affected in both men and women with AD compared to normal
      controls. However, only the men with AD displayed atrophy in the orbitofrontal
      cortex, middle and posterior cingulate cortices, hypothalamus, and mamillary
      bodies, and relative hypoperfusion in the anterior and middle cingulate cortices.
      Women with AD exclusively showed anterior thalamic atrophy. Separating men and
      women did not substantially improve diagnostic classification.

PMID- 15165702
TI  - Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease.
AB  - Sleep disturbance is a symptom shared by all neurodegenerative, dementing
      illnesses, such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB),
      and its presence frequently precipitates decisions to seek institutional care for
      patients. Although the sleep disturbances of AD and DLB are qualitatively
      similar, they appear to be more prominent in patients with DLB. Disturbance of
      the circadian rhythm has been noted and is a potential factor underlying the
      nocturnal sleep fragmentation and daytime sleepiness observed in these patients.
      We studied the circadian variation of core-body temperature and motor activity in
      a total of 32 institutionalized patients with probable AD by NINCDS-ADRDA
      criteria, 9 of whom also met pathologic criteria for DLB. Eight, healthy, elderly
      male controls were studied on a clinical research unit designed to simulate the
      hospital environment where the dementia patients were studied. Circadian
      variables generally had greater deviations from normal associated with increasing
      AD pathology, as measured by postmortem-determined Braak stage, supporting the
      hypothesis that central changes mediate circadian disturbances in AD and DLB.
      Patients with a postmortem diagnosis of DLB manifested greater disturbances of
      locomotor activity circadian rhythms than patients with AD, possibly reflecting
      the greater sleep disturbances seen in this population, but the differences from
      normal in the circadian rhythms of the AD and DLB patients were qualitatively
      similar.

PMID- 15165703
TI  - Thrombin, a mediator of neurotoxicity and memory impairment.
AB  - Thrombin has been found in neuritic plaques in Alzheimer's disease (AD). Also,
      traumatic brain injury, where neurons are exposed to high thrombin levels, is
      associated with an increased incidence of AD. Our objective was to determine the
      effects of thrombin administered in vivo on cognitive function and
      neuropathology. Rats were trained using a radial eight-arm maze and then thrombin
      (25 or 100 nM, 0.25 microl/h, 28 days) or vehicle was delivered via
      intracerebroventricular infusion. Animals that received 100 nM thrombin
      demonstrated cognitive impairments including deficits in reference memory and an
      increase in task latency. Also, significant neuropathology was detected in these
      animals such as enlargement of cerebral ventricles, an increased number of TUNEL
      positive cells, astrogliosis, and an increase in the immunoreactivity for
      phosphorylated neurofilament, and apolipoprotein-E fragments. Thrombin-induced
      changes in cognitive function and ventricular enlargement were inhibited by
      hirudin. These findings demonstrate that thrombin is a mediator of neurotoxicity
      and cognitive deficits and suggest that inhibition of thrombin may be a treatment
      strategy for AD- or head trauma-associated cognitive deficits.

PMID- 15165704
TI  - Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK
      and PI-3 kinase.
AB  - Ageing is accompanied by a myriad of changes, which lead to deficits in synaptic
      function and recent studies have identified an increase in concentration of the
      proinflammatory cytokine, interleukin-1beta (IL-1beta), as a factor which
      significantly contributes to deterioration of cell function. Here, we consider
      that increased IL-1beta concentration and upregulation of IL-1beta-induced cell
      signalling cascades may be accompanied by downregulation of survival signals,
      perhaps as a consequence of decreased neurotrophins-associated signalling. The
      data indicate that increased IL-1beta concentration was coupled with
      downregulation of ERK and phosphoinositide-3 kinase (PI-3 kinase) in cortical
      tissue prepared from aged rats. These changes could not be attributed to
      decreased concentration of NGF or BDNF but the evidence suggested that they may
      be a consequence of an age-related change in the anti-inflammatory cytokine, IL
      4. Significantly, treatment of aged rats with eicosapentaenoic acid reversed the
      age-related increases in IL-1beta and IL-1beta-induced signalling and also the
      age-related changes in IL-4, ERK and PI-3 kinase.

PMID- 15165705
TI  - Nefiracetam and physostigmine: separate and combined effects on learning in older
      rabbits.
AB  - Physostigmine and nefiracetam were tested alone and in combination in 104 rabbits
      with a mean age of 28 months conditioned in the 750 ms delay eyeblink classical
      conditioning procedure. In Experiment 1, five doses of physostigmine (0.0005-0.2
      mg/kg) enhanced conditioning. In Experiment 2, combinations of 10 mg/kg
      nefiracetam and 0.01, 0.1 and 0.2 mg/kg physostigmine improved the rate and
      magnitude of learning over rabbits treated with vehicle or 10 mg/kg nefiracetam
      alone. Brain AChE levels were significantly lower than vehicle for all doses of
      physostigmine and physostigmine plus nefiracetam. Control rabbits tested in the
      explicitly unpaired condition demonstrated that physostigmine alone and
      nefiracetam plus physostigmine had no non-associative effects. Physostigmine had
      a dramatic cognition-enhancing effect in older rabbits, and when nefiracetam was
      combined with physostigmine at a low dose, the ameliorating effect of
      physostigmine on learning was improved indicating that drug combinations for
      cognition enhancement may have therapeutic efficacy.

PMID- 15165706
TI  - Influence of aging on cortical activity associated with a visuo-motor task.
AB  - The aim of this study was to determine how cerebral aging influences the pattern
      of cortical oscillatory activity when a targeting movement with visual control is
      planned. Changes in cortical oscillatory activity were assessed by recording the
      event-related (de)synchronization (ERD/S) of micro and beta rhythms. Young and
      elderly subjects performed a distal movement, a proximal movement and a visuo
      guided targeting movement. Our results demonstrated an increase in micro ERD over
      ipsilateral regions and showed the spatial extent of micro ERD over
      parietocentral and parietal regions during motor planning in elderly subjects
      compared to young ones. After the movement, the beta ERS was significantly
      modified (a decrease in slope and amplitude) in elderly subjects. The most
      pronounced age-related changes in ERD/S pattern were observed for the targeting
      movement. Our results suggest that motor planning is less efficient in elderly
      subjects. This deficit might result from impaired parietal integrative function
      and/or changes in inputs from subcortical structures. Subsequently, the changes
      observed in the post-movement phase might reflect a decrease in (reafferent)
      sensory inputs and hence impaired their input processing.

PMID- 15165707
TI  - Neuropeptide chronomics in clinically healthy young adults: circaoctohoran and
      circadian patterns.
AB  - Endothelin-1 (ET-1) undergoes an about 8-h (circaoctohoran) rather than a
      circadian variation in clinical health. Herein, 24 h plasma concentrations of
      vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NpY), and
      cortisol used as reference, were obtained from 20 healthy young adults starting
      at 07:00 or 19:00 h. Like ET-1, SP and NpY undergo a circaoctohoran variation,
      whereas VIP is circadian rhythmic, peaking during the night, some 8 h prior to
      the circadian acrophase of cortisol. Maps of circadian and extra-circadian
      patterns may serve for screening, diagnosis and a better understanding of
      mechanisms underlying the etiology of various diseases.

PMID- 15165708
TI  - A potential antitumor peptide therapeutic derived from antineoplastic urinary
      protein.
AB  - New therapies in cancer treatment are focusing on multifaceted approaches to
      starve and kill tumors utilizing both antiangiogenic and chemotherapeutic
      compounds. Antineoplastic Urinary Protein (ANUP), a 32k Da protein normally
      secreted in human urine, has been previously described as a molecule possessing
      both antiproliferative and antiangiogenic activities. Two synthetic peptides
      complimentary to the N-terminus of ANUP were designed to test their ability to
      reproduce these beneficial effects but ultimately to provide a more useful small
      molecule therapeutic. The results show that the peptides reduced tumor burden by
      up to 70% in a nude mouse model and demonstrated the ability to inhibit blood
      vessel formation in a chick chorioallantoic membrane assay (CAM).

PMID- 15165709
TI  - Identification and characterization of peptides that bind to cyanovirin-N, a
      potent human immunodeficiency virus-inactivating protein.
AB  - Cyanovirin-N (CV-N) exerts a potent human immunodeficiency virus (HIV)
      inactivating activity against diverse strains of HIV by binding to the viral
      surface envelope glycoprotein gp120 and blocking its essential interactions with
      cellular receptors. Based on previous thermodynamic analyses, it has been
      speculated that discrete protein-protein interactions might play an important
      ancillary role in the CV-N/gp120 binding event, in addition to the interactions
      of CV-N with specific oligosaccharides present on gp120. Here, we report the
      identification and characterization of CV-N-binding peptides, which were isolated
      by screening of M13 phage-displayed peptide libraries. After performing three
      rounds of biopanning of the libraries against biotinylated CV-N, a CV-N-binding
      motif, X3CX6(W/F)(Y/F)CX2(Y/F), was evident. A vector was designed to express CV
      N-binding peptides as a fusion with thioredoxin (Trx) containing a penta-His
      affinity tag. The CV-N-binding peptides fused with His-tagged Trx inhibited
      binding of the corresponding peptide-bearing phages to CV-N, confirming that the
      peptides possessed CV-N-binding activity. Optical biosensor binding studies
      showed that the one of the CV-N-binding peptide, TN10-1, bound to CV-N with a KD
      value of 1.9 microM. The results of alanine scanning mutagenesis of the peptide
      showed that aromatic residues at positions 11, 12, and 16, as well as the
      conformational structure of the peptide secured by a disulfide bond, were
      important for the binding interactions. A series of competitive binding assays
      confirmed that gp120 inhibited CV-N binding of the corresponding peptide-bearing
      phages, and suggested that TN10-1 peptides were mimicking the protein component
      of gp120 rather than mimicking specific oligosaccharides present on gp120.

PMID- 15165710
TI  - Metabolism and absorption enhancement of methionine enkephalin in human nasal
      epithelium.
AB  - The objective of this study was to investigate absorption enhancing approaches
      for systemic delivery of methionine enkephalin via the nose. Absorption promotion
      of methionine enkephalin in the presence of protease inhibitors (bestatin,
      puromycin) and absorption enhancers (glycocholate, dimethyl-beta-cyclodextrin)
      were investigated in human nasal epithelium. Co-administration of the peptide
      with protease inhibitors and absorption enhancers resulted in a remarkable
      increase in Met-Enk permeation (4- to 94-fold). The increase was proportional to
      transepithelial resistance reduction and permeation of paracellular marker dye.
      Perturbation of the epithelial tight junctions seen in vitro may not occur in
      vivo due to mucus protection and mucociliary clearance.

PMID- 15165711
TI  - Opioid peptide response to spinal cord stimulation in chronic critical limb
      ischemia.
AB  - Twelve patients with chronic critical limb ischemia in whom a spinal cord
      stimulation (SCS) system had been implanted for at least one year had increased
      microvascular flow and achieved healing of trophic acral lesions. After switching
      off the system, the clinical improvement persisted for 10 days and the
      neurohormonal pattern showed high plasma values of beta-endorphin and Met
      enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric
      oxide. Met-enkephalin levels were further increased (P < 0.01) immediately after
      switching on the electrical stimulation again. The persistence of high plasma
      opioid levels after switching off the spinal cord stimulation explains the
      absence of subjective complaints and suggests an involvement of opioids in the
      regulation and improvement of the microcirculation.

PMID- 15165712
TI  - Supraspinal anti-allodynic and rewarding effects of endomorphins in rats.
AB  - Two potent endogenous opioid peptides, endomorphin-1 (EM-1) and -2 (EM-2), which
      are selective micro-opioid agonists, have been identified from bovine and human
      brain. These endomorphins were demonstrated to produce a potent anti-allodynic
      effect at spinal level. In the present study, we further investigated their
      supraspinal anti-allodynic effects and rewarding effects. In a neuropathic pain
      model (sciatic nerve crush in rats), EM-1 and -2 (15 microg, i.c.v.) both showed
      significant suppressive effects in the cold-water allodynia test, but EM-1 showed
      a longer duration than EM-2. Naltrexone (NTX; 15 microg) and naloxonazine (NLZ;
      15 microg) were both able to completely block the anti-allodynic effects of EM-1
      and -2. In the tests of conditioned place preference (CPP), only EM-2 at the dose
      of 30 microg showed significant positive rewarding effect, whereas both
      endomorphins did not induce any reward at the dose of 15 microg. Due to the low
      solubility and the undesired effect (barrel rotation of the body trunk), EM-1 was
      not tested for the dose of 30 microg in the CPP tests. It was also found that
      acute EM-2 (30 microg) administration increased dopamine turnover in the shell of
      nucleus accumbens in the microdialysis experiments. From these results, it may
      suggest that EM-1 and -2 could be better supraspinal anti-allodynic agents
      compared with the other opioid drugs, although they may also induce rewarding.

PMID- 15165713
TI  - The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks
      apomorphine but not MK-801-induced stereotypy in mice.
AB  - Bombesin (BN)-like peptides might be involved in the pathogenesis of
      neuropsychiatric disorders such as schizophrenia. Stereotyped behaviors induced
      by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate
      glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed
      as animal models of schizophrenic psychosis. In the present study we evaluated
      the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D
      Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801
      induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC
      3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The
      inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that
      induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior
      induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRP
      receptor antagonism blocks stereotyped behavior induced by a dopamine agonist.
      Together with previous evidence, the present study indicates that the BN/GRP
      receptor can be considered a drug target in the investigation of potential new
      agents for treating neuropsychiatric disorders.

PMID- 15165714
TI  - Distribution of adrenomedullin-containing perivascular nerves in the rat
      mesenteric artery.
AB  - Distribution of adrenomedullin (AM)-containing perivascular nerve fibers was
      studied in rat mesenteric arteries. Many fibers containing AM-like
      immunoreactivity (LI) were observed in the adventitia. AM-LI fibers were
      abolished by cold storage denervation or capsaicin but not 6-hydroxydopamine.
      Double immunostainings showed colocalization of AM-LI with calcitonin gene
      related peptide (CGRP)-LI. The dorsal root ganglia had many AM-positive cells and
      AM mRNA detected by RT-PCR. Electron microscopy study revealed high proportions
      of immunogold labeling for AM and colocalization of both AM-LI and CGRP-LI in
      unmyelinated nerve axons. These results suggest that AM-containing perivascular
      nerves are distributed in the rat mesenteric artery.

PMID- 15165715
TI  - The role of adrenomedullin and its receptor system in cardiovascular
      calcification of rat induced by Vitamin D(3) plus nicotine.
AB  - Adrenomedullin (ADM) is a potent vasodilatory peptide which regulates blood
      pressure, cell growth and bone formation. Our work was aimed to explore the
      production of ADM, changes and pathophysiological significance of ADM mRNA and
      ADM receptor components--calcitonin receptor like receptor (CRLR) and receptor
      activity modifying proteins (RAMPs) mRNA in calcified myocardium and aorta of
      rats induced by Vitamin D3 plus nicotine. Contents of ADM in plasma, myocardium
      and aorta were measured by radioimmunoassay (RIA). The amount of ADM, CRLR and
      RAMPs mRNA was determined by semi-quantitative RT-PCR. The calcium content and
      alkaline phosphatase activity in myocardium and aorta of rats were measured. The
      results showed that the contents of calcium in calcified myocardium and aorta
      were increased by 3.5- and 6-fold (all P < 0.01), respectively, and alkaline
      phosphatases activity in calcified myocardium and aorta were increased by 66.5
      and 82.7% (all P < 0.01 ), respectively, compared with control. Contents of ADM
      in plasma, myocardium and aorta were increased by 58% (P < 0.01), 14.3% (P <
      0.01) and 27.8% P < 0.05). Furthermore, it was found that the amount of ADM, CRLR
      and RAMP2 mRNA in calcified myocardium was elevated by 90.6, 157.5 and 119.6%
      (all P < 0.01), RAMP3 mRNA was decreased by 14.1% (P < 0.01), respectively,
      compared with control. The amount of ADM, CRLR, RAMP2 and RAMP3 mRNA in calcified
      aorta was elevated by 37.7% (P < 0.01), 41.4% (P < 0.01), 60.1% (P < 0.05) and
      13% P < 0.01), respectively, compared with control. The elevated level of CRLR
      and RAMP2 mRNA were in positive correlation with that of ADM mRNA (r = 0.992 and
      0.882, respectively, P < 0.01) in calcified myocardium. The elevated level of
      CRLR and RAMP3 mRNA were also in positive correlation with that of ADM mRNA (r =
      0.727, P < 0.05 and 0.816, P < 0.01, respectively) in calcified aorta. These
      results demonstrated that calcified myocardium and aorta generated an increased
      amount of ADM, up-regulated gene expressions of ADM, CRLR and RAMP2 mRNA. While
      the alteration of RAMP3 mRNA in calcified myocardium and aorta was different.
      These suggested that ADM and its receptor system might involve in the regulation
      of calcification in heart and aorta.

PMID- 15165717
TI  - Inhibitory effect of atriopeptinergic neurons in AV3V region on angiotensinII
      pressor system in rat brain.
AB  - In the central nervous system and the periphery, atrial natriuretic peptide (ANP)
      and angiotensinII(AngII) play important and opposite roles in regulating blood
      pressure and fluid electrolyte balance. Their central mechanisms are unclear. In
      the brain the anteroventral third ventricle region (AV3V) contains the most
      prominent collection of atriopeptin-like immunoreactive perikarya. Our previous
      studies show that: (1) AV3V stimulation by glutamate produces a fall in blood
      pressure; (2) there is an AngII pressor system composed of the lateral
      hypothalamus/perifornical region (LH/PF), subfornical organ (SFO), nucleus
      paraventricularis (NPV) and rostral ventrolateral medulla (RVL). The present
      study was to examine whether ANPergic projections from the AV3V could act on
      nuclei involved in the above-mentioned AngII pressor system. Here we demonstrate
      that: (1) Injection of atriopeptinIII into the LH/PF, SFO, NPV, or RVL induces a
      depressor response; whereas injection of normal saline has no effect. (2) Pre
      injection of A 71915 (an atriopeptinIII antagonist) into the LH/PF, SFO, NPV, or
      RVL reverses the depressor response of the AV3V to glutamate (Glu). The results
      suggest that excitation of atriopeptinergic neurons in the AV3V by Glu produces
      an inhibitory effect on each nucleus in the LH/PF-SFO-NPV-RVL AngII pressor
      system.

PMID- 15165716
TI  - Disassociated increases of adrenomedullin in the rat cerebrospinal fluid and
      plasma after salt loading and systemic administration of lipopolysaccharide.
AB  - To determine the role of adrenomedullin (AM) in the fluid electrolyte homeostasis
      and endotoxin shock, cerebral spinal fluid (CSF) and plasma were sampled from
      rats after respective challenges. The AM levels were measured by a highly
      sensitive immunoassay. The AM levels in the CSF of the rats anesthetized with
      ether (10.7 +/- 0.60 fmol/ml) were significantly higher than those with
      isoflurane 5.17 +/- 0.70 fmol/ml, P < 0.01), while the plasma level did not
      differ significantly. The CSF levels of the rats received 2% saline drinking
      increased to 3 and 4 folds at day 5 and day 7, respectively, while the plasma
      levels did not differ from controls at both time points. The AM levels in CSF or
      plasma increased to 1.5 and 3 folds at 1.5 h after intraperitoneal (i.p.)
      administration of lipopolysaccharide (LPS, 5 mg/kg), reached 6.5 and 30 folds at
      6 h, respectively, while no change was observed in the controls. The present
      findings suggest that AM in the CSF is regulated independently from that in the
      plasma, the centrally synthesized AM plays and important role in the regulation
      of the fluid electrolyte homeostasis. Furthermore, the circulatory AM plays an
      important role in the endotoxin shock.

PMID- 15165718
TI  - Isolation and characterization of a novel angiotensin I-converting enzyme
      inhibitory peptide derived from the edible mushroom Tricholoma giganteum.
AB  - The fruiting body of Tricholoma giganteum has many pharmaceutical uses and has
      long been utilized as a home remedy in Asia. This study describes the extraction
      and characterization of the first angiotensin I-converting enzyme (ACE)
      inhibitory peptide from T. giganteum. The maximum ACE inhibitory activity (IC50:
      0.31 mg) was obtained when the fruiting body of T. giganteum was extracted with
      distilled water at 30 degrees C for 3 h. After the purification of ACE inhibitory
      peptides with ultrafiltration, Sephadex G-25 column chromatography, and reverse
      phase HPLC, an active fraction with an IC50 of 0.04 mg and a yield of 0.3% was
      obtained. The ACE inhibitory peptide was a novel tripeptide, showing very low
      similarity to other ACE inhibitory peptide sequences, and was sequenced as Gly
      Glu-Pro. The purified ACE inhibitor from T. giganteum competitively inhibited
      ACE, and it maintained inhibitory activity even after incubation with proteases.
      ACE inhibitor from T. giganteum showed a clear antihypertensive effect in
      spontaneously hypertensive rats (SHR), at a dosage of 1 mg/kg.

PMID- 15165719
TI  - A conformation-constrained peptide library based on insect defensin A.
AB  - Here, we reported a conformation-constrained peptide library, that was
      constructed based on the scaffold of a 29 amino acids peptide derived from insect
      defensin A. The peptide scaffold was designed utilizing the InsightII molecular
      modeling software and then displayed on M13 filamentous bacteriophage by fusion
      with coat protein III. The library was constructed by randomization of seven
      positions located within the two loops of the peptide scaffold generating
      approximately 8.3 x 10(8) transformants. Sequences from 14 randomly selected
      phage clones indicated that the distribution of nucleotides and amino acids
      paralleled with the expected frequency. Screening against the target proteins:
      tumor necrosis factor alpha, TNF receptor 1, TNF receptor 2 and monoclonal
      antibody against BMP-2 showed significant enrichment in all cases. The results
      presented here show that the reconstructed insect defensin A domain will be a
      promising non-antibody protein scaffold for the presentation of a phage-displayed
      constrained peptide library.

PMID- 15165720
TI  - Kbot1, a three disulfide bridges toxin from Buthus occitanus tunetanus venom
      highly active on both SK and Kv channels.
AB  - On attempts to identify toxins showing original profile of activity among K+
      channels, we purified Kbot1, a scorpion toxin that blocks Kv1 and SK potassium
      channels. With 28 amino-acid residues, Kbot1 is the shortest toxin sequenced in
      Buthus occitanus scorpion. It is linked by three disulfide bridges and its
      primary structure is 93% identical to that of BmP02 isolated from the venom of
      the Chinese scorpion Buthus martensi Karsch [Eur. J. Biochem. 245 (1996) 457].
      Kbot1 exhibited a low neurotoxicity in mice after intracerebroventricular
      injection (LD50 approximately or = 0.8 microg per mouse). It competes with
      iodinated apamin for its rat brain synaptosomal membrane-binding site (IC50 of 20
      nM). Despite 30% sequence identity between Kbot1 and ChTX, competitive
      experiments on the [125I] charybdotoxin, show that Kbot1 inhibits its binding to
      its rat brain synaptosomes with IC50 of 10 nM. This result was supported by
      electrophysiological experiments on cloned voltage-dependent K+ channels from rat
      brain, expressed in Xenopus oocytes. Kbot1 blocks Kv1.1, Kv1.2 and Kv1.3 currents
      with IC50 of 145, 2.5 and 15 nM, respectively. Based on these data, Kbot1 may be
      considered as the first member of subfamily 9 of scorpion toxins [Trends
      Pharmacol. Sci. 20 (1999) 444], highly active on both Kv and SK channels.

PMID- 15165721
TI  - Valproate modulates TRH receptor, TRH and TRH-like peptide levels in rat brain.
AB  - We have tested our hypothesis that alterations in the levels of TRH receptors,
      and the synthesis and release of tripeptide TRH, and other neurotropic TRH-like
      peptides mediate some of the mood stabilizing effects of valproate (Valp). We
      have directly compared the effect of 1 week of feeding two major mood
      stabilizers, Valp and lithium chloride (LiCl) on TRH binding in limbic and extra
      limbic regions of male WKY rats. Valp increased TRH receptor levels in nucleus
      accumbens and frontal cortex. Li increased TRH receptor binding in amygdala,
      posterior cortex and cerebellum. The acute, chronic and withdrawal effects of
      Valp on brain levels of TRH (pGlu-His-Pro-NH2, His-TRH) and five other TRH-like
      peptides, Glu-TRH, Val-TRH, Tyr-TRH, Leu-TRH and Phe-TRH were measured by
      combined HPLC and RIA. Acute treatment increased TRH and TRH-like peptide levels
      within most brain regions, most strikingly in pyriform cortex. The fold increases
      (in parentheses) were: Val-TRH (58), Phe-TRH (54), Tyr-TRH (25), TRH (9), Glu-TRH
      (4) and Leu-TRH (3). We conclude that the mood stabilizing effects of Valp may be
      due, at least in part, to its ability to alter TRH and TRH-like peptide, and TRH
      receptor levels in the limbic system and other brain regions implicated in mood
      regulation and behavior.

PMID- 15165722
TI  - Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists
      urocortin II and urocortin III.
AB  - We compared the in vivo efficacy of two selective CRF2 agonists, mouse urocortin
      II (mUcn II) and human urocortin III (hUcn III), using food intake, anxious
      behavior, or ACTH release in CD-1 or Balb/c mice as indices of biological stress
      responses. All three peptides produced anorexia (Minimal Effective Dose (M.E.D.)
      for CRF and mUcn II = 0.03 nmol; M.E.D. for hUcn III = 0.3 nmol). Only mUcn II
      and CRF appeared to increase anxious behaviors in the elevated plus maze test
      (M.E.D. = 0.3 and 0.01 nmol, respectively). CRF increased the release of plasma
      ACTH (M.E.D. of 0.3 nmol), while mUcn II and hUcn III had no effect on ACTH
      release. These data suggest that the CRF2 receptor subtype plays a primary role
      in the activation of behavioral, but not neuroendocrine, stress responses.

PMID- 15165725
TI  - A new ribonuclease from the black oyster mushroom Pleurotus ostreatus.
AB  - A ribonuclease that is co-specific for poly C and poly U has been isolated from
      the fruiting bodies of the black oyster mushroom. The enzyme possesses a
      molecular mass of 14 kDa, and is unadsorbed on DEAE-cellulose and adsorbed on
      Affi-gel blue gel and CM-cellulose. A pH of 7 is required for the enzyme to
      exhibit maximal activity. The activity of the enzyme does not vary appreciably
      over the temperature range 30-60 degrees C, but drops when the temperature is
      reduced to 20 degrees C or raised to and above 70 degrees C. The ribonuclease
      does not exert any inhibitory activity toward HIV-1 reverse transcriptase.

PMID- 15165723
TI  - Increased hypothalamic melanin concentrating hormone gene expression during
      energy restriction involves a melanocortin-independent, estrogen-sensitive
      mechanism.
AB  - Increased expression of melanin concentrating hormone (MCH), an orexigenic
      neuropeptide produced by neurons in the lateral hypothalamic area (LHA), is
      implicated in the effect of energy restriction to increase food intake. Since
      melanocortins inhibit Mch gene expression, this effect of energy restriction to
      increase Mch signaling may involve reduced hypothalamic melanocortin signaling.
      Consistent with this hypothesis, we detected increased hypothalamic Mch mRNA
      levels in agouti (Ay) mice (by 102%; P < 0.05), a model of genetic obesity
      resulting from impaired melanocortin signaling, compared to wild-type controls.
      If reduced melanocortin signaling mediates the effect of energy restriction,
      hypothalamic Mch gene expression in Ay mice should not be increased further by
      energy restriction, since melanocortin signaling is impaired in these animals
      regardless of nutritional state. We therefore investigated the effects of energy
      restriction on hypothalamic Mch gene expression in both Ay mice and in wild-type
      mice with diet-induced obesity (DIO). Responses in these mice were compared to
      those induced by administration of 17beta-estradiol (E2) at a dose previously
      shown to reduce food intake and Mch expression in rats. In both Ay and DIO mice,
      energy restriction increased hypothalamic Mch mRNA levels (P < 0.05 for each) via
      a mechanism that was fully blocked by E2. However, E2 did not lower levels of Mch
      mRNA below basal values in Ay mice, whereas it did so in DIO mice. Thus, the
      effect of energy restriction to increase hypothalamic Mch gene expression
      involves an E2-sensitive mechanism that is not altered by impaired melanocortin
      signaling. By comparison, impaired melanocortin signaling increases hypothalamic
      Mch gene expression via a mechanism that is insensitive to E2. These findings
      suggest that while both energy restriction and reduced melanocortin signaling
      stimulate hypothalamic Mch gene expression, they do so via distinct mechanisms.

PMID- 15165726
TI  - Adustin, a small translation-inhibiting polypeptide from fruiting bodies of the
      wild mushroom Polyporus adusta.
AB  - A polypeptide, with a molecular mass of 16.5 kDa as determined by gel filtration
      and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, has been isolated
      from the mushroom Polyporus adusta. The polypeptide, designated as adustin,
      inhibited translation in a cell-free rabbit reticulocyte lysate system with an
      IC50 of 0.34 microM. It was isolated using a protocol that involved ion exchange
      chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel,
      ion exchange chromatography on CM-Sepharose and fast protein liquid
      chromatography-gel filtration on Superdex 75. Adustin was unadsorbed on DEAE
      cellulose, and adsorbed on Affi-gel blue gel and CM-Sepharose.

PMID- 15165724
TI  - The interaction of an antimicrobial decapeptide with phospholipid vesicles.
AB  - Previously, by using combinatorial peptide libraries, we have identified activity
      optimized decapeptide (KSL, KKVVFKVKFK-NH(2)), which exhibited a broad spectrum
      of the activity against bacteria and fungi without hemolytic activity. In order
      to examine lipid requirements and to understand the mode of KSL action, we
      investigated interactions of the peptide with vesicles consisting of various
      lipid compositions. KSL increased the permeability of negatively charged but not
      zwitterionic phospholipid membranes, and the leakage was independent on the size
      of encapsulated molecules (calcein, 1-aminonaphthalene-3,6,8-trisulfonic acid
      (ANTS)/N,N'-p-xylene bis(pyridinium) bromide (DPX), and fluorescein
      isothiocyanate (FITC)-dextran with different molecular weight), indicating that
      the peptide did not form pores or channels in this leakage process. KSL ability
      to permeabilize vesicles with negatively charged surface was dramatically reduced
      upon the addition of zwitterionic phospholipid rather than cholesterol, which
      revealed that the surface charge of lipid membranes played a major role in the
      activity and selectivity of KSL. Moreover, KSL diastereomer did not increase the
      permeability of negatively charged vesicles, indicating that the secondary
      structure of KSL was also required for membrane perturbation activity.
      Interestingly, KSL had an ability to cause aggregation and subsequent fusion of
      the acidic vesicles, which seemed to be related to the biological action.
      Structural studies performed by circular dichroism (CD) spectroscopy indicated
      that in the presence of acidic vesicles, the beta sheet structure of KSL must be
      required for the ability to (1) induce a leakage of dye from the acidic vesicles
      (2) to fuse the acidic vesicles.

PMID- 15165727
TI  - Alveolarin, a novel antifungal polypeptide from the wild mushroom Polyporus
      alveolaris.
AB  - An antifungal polypeptide, with a molecular mass of 28 kDa as judged by gel
      filtration and appearing as a single band with a molecular mass of 14 kDa in
      sodium dodecyl suflate-polyacrylamide gel electrophoresis, was isolated from
      fresh fruiting bodies of the mushroom Polyporus alveolaris. The antifungal
      polypeptide, designated as alveolarin, demonstrated an inhibitory action on
      mycelial growth in Botrytis cinerea, Fusarium oxysporum, Mycosphaerella
      arachidicola and Physalospora piricola. Alveolarin was isolated with a procedure
      that entailed ion exchange chromatography on DEAE-cellulose, affinity
      chromatography on Affi-gel blue gel, and gel filtration on Superdex 75 by fast
      protein liquid chromatography.

PMID- 15165728
TI  - Endogenous opioids and feeding behavior: a 30-year historical perspective.
AB  - This invited review, based on the receipt of the Third Gayle A. Olson and Richard
      D. Olson Prize for the publication of the outstanding behavioral article
      published in the journal Peptides in 2002, examines the 30-year historical
      perspective of the role of the endogenous opioid system in feeding behavior. The
      review focuses on the advances that this field has made over the past 30 years as
      a result of the timely discoveries that were made concerning this important
      neuropeptide system, and how these discoveries were quickly applied to the
      analysis of feeding behavior and attendant homeostatic processes. The discoveries
      of the opioid receptors and opioid peptides, and the establishment of their
      relevance to feeding behavior were pivotal in studies performed in the 1970s. The
      1980s were characterized by the establishment of opioid receptor subtype agonists
      and antagonists and their relevance to the modulation of feeding behavior as well
      as by the use of general opioid antagonists in demonstrating the wide array of
      ingestive situations and paradigms involving the endogenous opioid system. The
      more recent work from the 1990s to the present, utilizes the advantages created
      by the cloning of the opioid receptor genes, the development of knockout and
      knockdown techniques, the systematic utilization of a systems neuroscience
      approach, and establishment of the reciprocity of how manipulations of opioid
      peptides and receptors affect feeding behavior with how feeding states affect
      levels of opioid peptides and receptors. The role of G-protein effector systems
      in opioid-mediated feeding responses, which was the subject of the prize-winning
      article, is then reviewed.

PMID- 15165730
TI  - Organizing pains.
AB  - Chronic pain is sustained by central neuronal sensitization, with many similar
      characteristics irrespective of the type of injury incurred. Nevertheless, pain
      arising from nerve injury (neuropathic pain) is resistant to centrally acting
      analgesics, whereas inflammatory pain responds well. New research indicates that
      the role of spinal NMDA receptors in chronic pain depends on adaptor proteins of
      the membrane-associated guanylate kinase (MAGUK) family and raises the
      possibility that complexes of different composition might contribute
      differentially to different pain states.

PMID- 15165731
TI  - Neuron-glia interactions clarify genetic-environmental links in mental illness.
AB  - How genes and environment interface to generate major psychiatric disorders such
      as schizophrenia has been puzzling, as are the relative roles of neurons and glia
      in such disturbances. Tomonaga and colleagues have recently reported striking
      neurobehavioral abnormalities in mice expressing Borna disease virus
      phosphoprotein (BDV-P) selectively in glial cells. The study provides a novel
      approach of linking environmental and genetic factors to behavior by producing
      genetically engineered mice. The key role for glial BDV-P implicates neuron-glia
      interactions in the pathogenesis of psychiatric conditions.

PMID- 15165732
TI  - Structural changes during ion channel gating.
AB  - Ion channels are generally multi-subunit complexes, with the ion conduction
      pathway formed at the subunit interface. In moving between the closed and open
      states, three structurally distinct channels, represented by the recently
      determined structures of a mechanosensitive, ligand-gated and K(+) selective
      channel, all move transmembrane helices away from the central ion conduction
      pathway. In all three cases, this results in the displacement of a hydrophobic
      gate from the ion conduction pathway, freeing ion movement. The channels achieve
      this by moving the transmembrane helices as rigid bodies using three major types
      of motion: MscL tilts its helices, the nicotinic ACh receptor rotates its
      helices, and KirBac1.1 bends its helices. In all cases, the gating motions are
      likely to take place rapidly. These large and fast movements provide a possible
      explanation for why the conduction pathways of a wide range of different ion
      channels are formed at the interface between subunits.

PMID- 15165733
TI  - Stirring up controversy with a voltage sensor paddle.
AB  - Neurons owe their exquisite electrical excitability to voltage-gated ion
      channels. By creating and shaping the action potential, these voltage-sensitive
      proteins supply the neuron with crucial communication skills. A steady stream of
      experimental results, arising from numerous laboratories and employing a diverse
      repertoire of techniques, has produced a consensus model of the way voltage-gated
      ion channels sense and respond to changes in membrane potential. In contrast to
      this consensus mechanism, recent studies of the voltage-gated K(+) channel KvAP
      suggest a strikingly different mode of action. In this review, these disparate
      models are compared and critically discussed.

PMID- 15165734
TI  - Permeation in ion channels: the interplay of structure and theory.
AB  - Combined with high-resolution atomic-level crystal structures of channel forming
      peptides, theory has become a powerful tool for illuminating factors influencing
      permeation. Here, advantages and limitations of the more familiar continuum and
      molecular modeling techniques are briefly outlined. These methods are applied to
      issues of permeation in two different channel families: gramicidin and K(+)
      channels. Using structural data, theory provides verifiable atomic-level insights
      into permeation dynamics, channel conductance and molecular selectivity
      mechanisms. Not only can theory confirm experimental inference, it can also
      sometimes provide structural perspectives in advance of experiment.

PMID- 15165735
TI  - The structural basis of ClC chloride channel function.
AB  - ClC channels constitute a large family of Cl(-)-selective ion channels that are
      present in diverse organisms. The channels have a complex gating behavior, in
      which channel opening and closing is tightly coupled to ion permeation. Recent
      success in the structure determination of bacterial channels has revealed the
      overall architecture of this family and provided important insight into ion
      selectivity and gating. The ClC channels are homodimers, with each subunit
      containing an ion conduction pore. In the narrow selectivity filter of each pore,
      Cl(-) are bound to several sites through electrostatic interactions with helix
      dipoles and the partial charges of protein residues. In the closed conformation
      of the channel, a conserved glutamate residue occupies one of the ion-binding
      sites; on channel opening, this glutamate residue moves out of the binding site,
      thereby making room for an additional Cl(-) ion.

PMID- 15165736
TI  - Structure and gating of the glutamate receptor ion channel.
AB  - Ionotropic glutamate receptors are ligand-gated ion channels that mediate rapid
      information transfer at most excitatory synapses in the brain. Crystal structures
      are now available for the ligand-binding domain, but the structure of the ion
      channel itself remains unknown. The core of the ion channel shares structural
      features with an inverted K(+) channel. In detail, however, differences are
      emerging. Most notable in the glutamate receptor ion channel are distinct
      structural and functional properties of a major pore-lining domain, the
      requirement of an additional transmembrane segment (M4), and twofold rather than
      fourfold symmetry. Together with ligand-binding domain structures and kinetic
      experiments, these findings have started to define the basic principles of
      channel gating in glutamate receptors.

PMID- 15165737
TI  - Cys-loop receptors: new twists and turns.
AB  - New hypotheses and predictions have arisen from recent work revealing atomic
      scale or near-atomic-scale structures of receptors in the 'Cys-loop' superfamily.
      How general is the cation-pi interaction between the natural ligand and a
      tryptophan residue in the aromatic box, and does this interaction extend to other
      ligands? What is the pathway from the binding site to gating, and what are the
      conformational changes during gating and desensitization? Is current flow through
      intracellular 'portals' in the wall of the channel a general feature? This
      article discusses these and related questions, emphasizing nicotinic ACh
      receptors and also discussing data from other members of this superfamily.

PMID- 15165738
TI  - Function and structure in glycine receptors and some of their relatives.
AB  - In the field of ligand-gated ion channels, recent developments, both in the
      knowledge of structure and in the measurement of function at the single-channel
      level, have allowed a sensible start to be made on understanding the relationship
      between structure and function in these proteins. In this review, the cases of
      glycine, nicotinic ACh and glutamate receptors are compared and contrasted, and
      problems such as how binding of agonist causes the channel to open, and why
      partial agonists are partial, are considered. Some observations, both structural
      and functional, suggest that more attention needs to be paid to conformational
      changes that occur before the channel opens. Such changes might account for the
      interaction found between subunits of the glycine receptor while it is still shut
      and, perhaps, the agonist-dependent structural changes seen in AMPA receptors.
      They might also complicate our understanding of the binding-gating problem.

PMID- 15165740
TI  - Transporter structure and mechanism.
AB  - During the past several decades, lac permease has assumed almost tutelary
      proportions as a model for cotransporters. This archetypical membrane protein now
      exerts its influence by the most dramatic means possible: its structure is
      solved. This article describes the configuration and implied transport mechanism
      of the bacterial lactose transporter and compares its structure and function with
      those of other transporters and those of ion channels. This juxtaposition of
      transporters and channels is likely to be helpful because LacY is the first
      cotransporter with known structure and exclusive carrier properties, and it
      shares topology with neurotransmitter transporters with unknown structure and
      channel properties.

PMID- 15165739
TI  - Mechanosensitive channels: what can we learn from 'simple' model systems?
AB  - Mechanosensitive ion channels, which convert external mechanical forces into
      electrical and chemical signals in cells, are diverse. Presently, there is no
      known common sequence 'signature' that identifies mechanosensitivity. Bacterial
      mechanosensitive channels gated by membrane tension represent convenient models
      allowing us to combine structural information with the insights gained from
      biophysical analysis, biochemistry, genetic screens, bacterial physiology and
      molecular computation. Here, the conformational transition driven by membrane
      tension in the bacterial channel MscL is discussed. The predicted pathway
      suggests roles for distinct protein domains, surrounding lipids and water in the
      gating process. MscL, a simple system, thus helps us obtain a coherent picture of
      molecular events, and build concepts and strategies that can be applied to more
      elaborate mechanosensory systems in the near future.

PMID- 15165741
TI  - ACE2: from vasopeptidase to SARS virus receptor.
AB  - The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only
      known human homologue of the key regulator of blood pressure angiotensin
      converting enzyme (ACE). Since its discovery in 2000, ACE2 has been implicated in
      heart function, hypertension and diabetes, with its effects being mediated, in
      part, through its ability to convert angiotensin II to angiotensin-(1-7).
      Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute
      respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for
      pharmacological intervention on several disease fronts.

PMID- 15165742
TI  - S-Adenosylhomocysteine hydrolase as a target for intracellular adenosine action.
AB  - S-Adenosylhomocysteine hydrolase (AdoHcyase) controls intracellular levels of S
      adenosylhomocysteine (AdoHcy). AdoHcy is a potent product inhibitor of some S
      adenosylmethionine-dependent methyltransferases. Pharmacological modulation of
      AdoHcyase to indirectly inhibit methyltransferases can be guided by the fact that
      adenosine binds with high affinity to AdoHcyase and inhibits enzyme activity.
      cAMP can compete with adenosine and can counteract the adenosine-induced
      inhibition of AdoHcyase. Thus, the ratio between adenosine and cAMP, which can
      vary under different physiological conditions, might result in changes in, for
      example, DNA promoter methylation and therefore transcription.

PMID- 15165743
TI  - An insight into Malaysian herbal medicines.

PMID- 15165744
TI  - Pain-like behaviours in animals - how human are they?
AB  - The use of genetically manipulated animals in conjunction with classical
      physiological and biochemical measurement has unravelled many pathological
      changes in animal models of chronic pain that bear some striking similarities to
      those described in several chronic pain conditions in humans. In this article, I
      highlight several limitations in the validation of animal models of chronic pain
      and the methods that are used for assessing pain-like behaviours in these models.
      Alternative methods for assessing pain and stress in animals, which might better
      reflect the diverse symptomotology of chronic pain in humans, are proposed.

PMID- 15165745
TI  - Intravenous immunoglobulin for infectious diseases: back to the pre-antibiotic
      and passive prophylaxis era?
AB  - The dramatic increase in both the number of novel infectious agents and
      resistance to antimicrobial drugs has incited the need for adjunct therapies in
      the war against infectious diseases. Exciting recent studies have demonstrated
      the use of antibodies in the form of intravenous immunoglobulin (IVIg) against
      infections. By virtue of the diverse repertoire of immunoglobulins that possess a
      wide spectrum of antibacterial and antiviral specificities, IVIg provides
      antimicrobial efficacy independently of pathogen resistance and represents a
      promising alternative strategy for the treatment of diseases for which a specific
      therapy is not yet available.

PMID- 15165746
TI  - Nitric oxide, S-nitrosothiols and hemoglobin: is methodology the key?
AB  - Two main hypotheses describe the role of hemoglobin in the regulation of nitric
      oxide (NO) bioavailability. It has been suggested that hemoglobin interacts with
      circulating NO, forming Fe-nitrosyl hemoglobin and then S-nitrosothiols, which
      deliver NO extracellularly by an allosterically regulated mechanism.
      Alternatively, the existence of diffusional barriers that protect NO from
      hemoglobin-mediated degradation has been proposed. The reliability of each model
      in vivo is supported by the detection of physiological hematic levels of S
      nitrosohemoglobin. However, the measured concentrations of S-nitrosohemoglobin
      are largely divergent between the two models. Moreover, recent reports suggest
      that circulating levels of S-nitrosohemoglobin in human blood could be
      significantly lower than assessed previously. We suggest that solving the
      methodological controversies that make the field of NO research a 'minefield',
      even for skilled analysts, is fundamental to understanding the role of S
      nitrosothiols in the vasculature.

PMID- 15165747
TI  - Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
AB  - Neuronal nicotinic acetylcholine (nACh) receptors in the brain are more commonly
      associated with modulatory events than mediation of synaptic transmission. nACh
      receptors have a high permeability for Ca(2+), and Ca(2+) signals are pivotal in
      shaping nACh receptor-mediated neuromodulatory effects. In this review, we
      consider the mechanisms through which nACh receptors convert rapid ionic signals
      into sustained, wide-ranging phenomena. The complex Ca(2+) responses that are
      generated after activation of nACh receptors can transmit information beyond the
      initial domain and facilitate the interface with many intracellular processes.
      These mechanisms underlie the diverse repertoire of neuronal activities of
      nicotine in the brain, from the enhancement of learning and memory, to addiction
      and neuroprotection.

PMID- 15165748
TI  - Signaling pathways involved in the development of cannabinoid tolerance.
AB  - Considerable plasticity exists in the endogenous cannabinoid system, as evidenced
      by the high degree of tolerance that develops following repetitive exposure to
      exogenously administered cannabinoid receptor agonists. This tolerance
      development is accompanied by cannabinoid CB(1) receptor downregulation and
      attenuation of G-protein activation. The biological processes responsible for
      CB(1) receptor downregulation remain to be fully understood. However, recent
      evidence suggests that several protein kinases participate in the development of
      cannabinoid tolerance. These observations implicate a role for protein kinases in
      cannabinoid signaling pathways. It remains to be established whether these
      protein kinases are directly involved in CB(1) receptor regulation or whether
      they contribute to tolerance by modulating additional signaling pathways.

PMID- 15165749
TI  - Peroxisome proliferator-activated receptor gamma in diabetes and metabolism.
AB  - The peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been the
      focus of intense research during the past decade because ligands for this
      receptor have emerged as potent insulin sensitizers used in the treatment of type
      2 diabetes. Recent advances include the discovery of novel genes that are
      regulated by PPAR-gamma, which helps explain how activation of this adipocyte
      predominant transcription factor regulates glucose and lipid homeostasis.
      Increased levels of circulating free fatty acids and lipid accumulation in non
      adipose tissue have been implicated in the development of insulin resistance.
      This situation is improved by PPAR-gamma ligands, which promote fatty acid
      storage in fat depots and regulate the expression of adipocyte-secreted hormones
      that impact on glucose homeostasis. The net result of the pleiotropic effects of
      PPAR-gamma ligands is improvement of insulin sensitivity, although undesired side
      effects limit the utility of this therapy. It might be possible to dissociate the
      anti-diabetic and adverse effects through selective modulation of PPAR-gamma
      activity.

PMID- 15165750
TI  - Techniques: reporter mice - a new way to look at drug action.
AB  - During the past decade remarkable progress in molecular genetics and the
      possibility of manipulating cells so that the expression of genes can directly
      'report' on drug activity has produced major changes in drug development
      strategies. The recent description and pharmacological validation of reporter
      mice for in vivo analysis of hormone receptor activity opens new horizons for
      drug discovery. These novel animal models, in association with in vivo imaging
      technologies, provide a global view of the target tissues of drug action
      following acute and repeated drug treatment, thus enabling the prediction of
      potential side-effects in the early phase of preclinical studies. It is
      anticipated that further improvements of transgene architecture will lead to
      models that combine pharmacokinetic, pharmacodynamic and toxicological studies in
      a single step, which should provide a tremendous saving in time and,
      paradoxically, the number of animals to be sacrificed in the development of novel
      pharmacologically active molecules.

PMID- 15165751
TI  - A simple and sensitive method for glutamine:fructose-6-phosphate amidotransferase
      assay.
AB  - For measuring glutamine:fructose-6-phosphate amidotransferase (GFAT) activity in
      cultured cells, an enzyme method -GDH method- was set up with high-efficiency,
      high-sensitivity and simple operation by determining the formed glutamate. During
      the process of making samples, reduced glutathione (GSH, 5 mM) and glucose-6
      phosphate Na2 (5 mM) were added to the buffer for scraping the cells. The range
      of protein content in the samples was 80-150 microg. In the GFAT activity assay,
      the end product reduced acetylpyridine adenine dinucleotide (APADH) was
      determined at 370 nm directly. The suitable concentrations of the reactants
      fructose-6-phosphate (F-6-P), glutamine, acetylpyridine adenine dinucleotide
      (APAD) and glutamate dehydrogenase (GDH) were 0.8, 6 and 0.3 mM and 6 U,
      respectively. However, the excess of APAD may interfere with the APADH
      measurement. The reaction time course was 90 min. The GFAT activity in 3T3-L1,
      L6, HepG2 and HIRc cells were 1.84-8.51 nmol glutamate/mg protein.min.

PMID- 15165753
TI  - A quantitative real-time PCR assay for the detection of tetR of Tn10 in
      Escherichia coli using SYBR Green and the Opticon.
AB  - Bacteria of implant infections are extremely resistant to antibiotics. One reason
      for this antibiotic resistance are transposons; the well-known transposon Tn10,
      for example, mediates tetracycline resistance to Escherichia coli. Two genes of
      Tn10, tetA and tetR, are essential for the mechanism of resistance. These genes
      encode a drug-specific efflux protein and a tetracycline repressor protein,
      respectively. Tn10 is also widely used in molecular biology. For example, tTA, a
      recombinant derivate of tetR, has been utilised for a highly efficient gene
      regulation system in mammalian cells. We have examined E. coli isolates from
      implant infections for tetracycline resistance and for the presence of tetR. A
      real-time PCR assay was developed for detection of tetR with SybrGreen using the
      Opticon PCR machine of MJ Research. This method offers a quick, sensitive,
      efficient, and reliable approach to the detection and quantification of genes.
      Clinical isolates of E. coli were examined successfully for tetracycline
      resistance and for the presence of tetR. The real-time PCR is effective using a
      variety of templates including isolated E. coli DNA, pure colonies, or liquid
      culture sources. Using quantified standard DNA, this assay can accurately detect
      as few as 15 copies. Moreover, this assay has the ability to quantify the number
      of tetR genes in the presence of contaminating mammalian DNA. In conclusion, the
      tetR real-time PCR offers new methods for detection and quantification of
      tetracycline-resistant bacteria and tTA in transfected cell-lines or transgenic
      animals.

PMID- 15165752
TI  - Small amounts of urea and guanidine hydrochloride can be detected by a far-UV
      spectrophotometric method in dialysed protein solutions.
AB  - The quantization of small amounts of chemical denaturants as urea or guanidine
      hydrochloride in protein solutions after dialysis is a difficult task in the
      molecular biology laboratory practice. Refractometric methods are useful to
      quantify a denaturant in the molar range but this methodology is not helpful when
      the denaturant is present in small amounts. The method herein described is a new
      comparative method that requires, a priori, the quantification of the stock
      solutions of urea (8 M) and guanidine hydrochloride (6 M) by refractometry to
      prepare by sequential dilution the standards used for comparison in the
      spectropolarimeter. The method is based on the observation that the wavelengths,
      at which the absorbance of polarized light increases in the far-UV region, as
      observed by spectropolarimetry, is related to the concentration of the chemical
      denaturant present in the protein solution. In the quantitation method herein
      reported, the urea and guanidine hydrochloride detection limits range from 1.2 x
      10(-4) to 6 x 10(-6) M depending on the protein dialysis buffer used for a
      standard cell path length of 1 cm. The sensibility of this method results to be
      comprised in a range 4-5 orders of magnitude higher than that measured by
      refractometry. The determinations in both the sample and the control preparations
      are virtually completed within approximately 10 min.

PMID- 15165755
TI  - A simple method to determine trypsin and chymotrypsin inhibitory activity.
AB  - A colorimetric method for serine protease inhibition was modified using N-Acetyl
      DL-Phenylalanine beta-Naphthylester (APNE) as the substrate and o-Dianisidine
      tetrazotized (oD) as the dye. The reaction generated a single peak absorbing at
      530 nm for both trypsin and chymotrypsin. Standard curves with increasing enzyme
      concentrations showed strong linearity. A standard curve for the serine protease
      inhibitor, Bowman-Birk Inhibitor (BBI), has been made using this modified method.
      The IC50 for 3 U of trypsin was found to be 33 ng and the IC50 obtained for 3 mU
      of chymotrypsin was 53 ng. A recombinant BBI (rBBI) gene was constructed, cloned
      and expressed in the yeast Pichia pastoris. Evaluating samples of rBBI for
      protease inhibitory activity by the gel activity method failed to quantify the
      inhibitor amounts, due to high sensitivity for trypsin inhibition and low
      sensitivity for chymotrypsin inhibition. After development, the results could not
      be quantified, even to the extent that 1 microl of rBBI could not be detected
      with chymotrypsin inhibition. Therefore, a modified method for trypsin and
      chymotrypsin inhibition was used to evaluate the level of rBBI-expression for
      these same samples. The level of rBBI expression was calculated to be 50-56
      ng/microl of media. These amounts fit into the range of values previously
      obtained by Western blot analysis. This modified method allows us to combine the
      sensitivity of the gel activity method with the quantification attributes of a
      Western blot. Thus, the modified method represents a significant improvement in
      speed, sensitivity and reproducibility over the gel activity method.

PMID- 15165756
TI  - A novel approach for reliable activity determination of ascorbic acid depending
      myrosinases.
AB  - Up to now, a wide array of methods for the determination of myrosinase activity
      has been described. These vary from the simple photometric estimation to highly
      sophisticated assays using radioactively labelled substrates. However, ascorbic
      acid--an effective activator of myrosinases--interferes with most of these enzyme
      tests. Unfortunately, in the past, such interferences were disregarded in many
      scientific examinations of myrosinases. Whereas such failings have less effects
      when the activation of myrosinases is not very distinctive, they are quite
      relevant in all cases where myrosinases are completely inactive in the absence of
      ascorbic acid. In this paper, the current methods for myrosinase determination
      are reviewed critically with special emphasis on putative interferences with
      ascorbic acid. Thereafter, an alternative and interference-free HPLC-based
      quantification method of the enzymatically produced glucose is presented. Due to
      the benzoylation of glucose, it becomes possible to quantify even those exiguous
      glucose concentrations, which are indispensable for correct determination of
      kinetic enzyme data in the presence of ascorbic acid. Using this new method, the
      activity of Tropaeolum majus myrosinase towards glucotropaeolin was analyzed.
      This enzyme shows a distinctive activation by ascorbic acid with maximal
      activation at a concentration of about 2 mM.

PMID- 15165754
TI  - Miniaturisation and validation of a cell-based assay for screening of Ca2+
      channel modulators.
AB  - Voltage-operated calcium channels (VOCCs) play a significant role in the
      regulation of intracellular calcium concentrations in cardiovascular, neuronal
      and skeletal tissues. Therefore, physiologically relevant screening methods for
      calcium channel modulators are required. A 45Ca2+ uptake assay based on clonal
      rat pituitary cell line GH4C1, possessing L-type VOCCs, was miniaturised into a
      96-well plate format. The assay was validated by known Ca2+ channel blockers,
      verapamil and nimodipine (IC50 values 3.4 and 0.007 microM, respectively) and by
      a set of natural compounds and their synthetic derivatives. The results were
      consistent with our previous data and demonstrated the reliability of the assay.
      The signal-to-background ratio was 3.9 +/- 0.4, signal-to-noise ratio 10.3 +/-
      2.3, Z' factor 0.59 +/- 0.10, and day-to-day variability in positive control
      values 5%. Furthermore, experiments were also made on a Biomek FX workstation to
      evaluate the suitability of the assay for automation. With minor modifications
      the assay is applicable, e.g. for studying possible Ca2+ channel activators in
      detail. The established 96-well plate assay modification for screening of calcium
      channel modulators reduces considerably the time, labour and resources needed for
      cell culture and experiments, and has significant advantages in terms of
      automation suitability and overall cost-efficiency.

PMID- 15165758
TI  - Urinary neopterin quantification by reverse-phase high-performance liquid
      chromatography with ultraviolet detection.
AB  - Neopterin plays an important role in the malignant disease diagnostics. However,
      the methods employed in neopterin determination are generally difficult and/or
      time consuming. The aim of this work was to standardize a practical method to
      quantify neopterin using high-performance liquid chromatography-ultraviolet (HPLC
      UV) and quantify it in patients with systemic lupus erythematosus (SLE). Urine
      was collected from healthy subjects (n= 49), patients with inactive (n= 15),
      active (n= 28), and highly active SLE (n= 6). The HPLC was performed using two
      coupled reverse-phase columns eluted with 150 mM sodium phosphate, pH 4.0, under
      a flow rate of 0.8 ml/min, with UV detector set at 353 nm and 100-fold diluted
      urines. The inter- and intra-assay studies presented an imprecision of 12.5% and
      12.9% for quality controls of 3.94 and 1.1 micromol/ml, respectively. Recovery
      from 79.5% to 82% was observed throughout the assay's linear range. Subjects with
      active (874.2 +/- 165.38 micromol/mol creatinin) and highly active SLE (1753.8 +/
      453.9 micromol/mol creatinin) showed three- and sixfold increased neopterin
      levels, respectively, compared to subjects with inactive SLE (314.3 +/- 121.3
      micromol/mol creatinin) and healthy subjects (294.6 +/- 178.6 micromol/mol
      creatinin) (P< 0.05). Briefly, the proposed method was precise, specific, and
      reproducible, not invasive and allows the urinary neopterin quantification only
      with UV detection.

PMID- 15165757
TI  - Microcalorimetric investigation on the growth model and the protein yield of
      Bacillus thuringiensis.
AB  - A novel microcalorimetric technique based on the bacterial heat output was
      applied to evaluate the special growth model, the protein expression and the
      generation time of Bacillus thuringiensis for the first time. The thermogenic
      curves of the aerobic metabolism of B. thuringiensis strains YBT-833, YBT-1520
      and YBT-833-2-1 were determined by using an LKB-2277 BioActivity Monitor. The
      analysis of the thermogenic curves indicated both the mutant strain and the wild
      type strains followed the same linear growth model during sporulation. The
      metabolism heat output revealed heat output was correlated to the yield of the
      insecticidal crystal proteins (ICPs) very well, the more protein product, and the
      less heat output. Based on the data acquired, we proposed that this method could
      be a useful tool in monitoring the fermentation of B. thuringiensis.

PMID- 15165759
TI  - Three-year-old boy with burn wound sepsis: a challenge to the ethics of a
      responsible surgeon.

PMID- 15165761
TI  - Is there a place for aggressive surgery in stage IV breast cancer?

PMID- 15165760
TI  - Hypertonic saline: here we go again?

PMID- 15165762
TI  - Metalloproteinases: promising tumor markers for breast cancer management.

PMID- 15165763
TI  - Optimal surgeon experience for breast cancer sentinel node biopsy: how can
      surgeons stay up-to-date?

PMID- 15165764
TI  - PET scans in general surgery: current status in their use for general surgery.

PMID- 15165765
TI  - Geriatric assessment-minimizing the risks.

PMID- 15165767
TI  - Competency in surgery. surgical complications/outcomes: should we be doing
      better?

PMID- 15165766
TI  - Perioperative nutrition and metabolism in geriatric surgical patients.

PMID- 15165768
TI  - Choledocholithiasis--principles of diagnosis and management.

PMID- 15165769
TI  - Laparoscopic common bile duct exploration.

PMID- 15165770
TI  - Abdominal pain in a young man with AIDS.

PMID- 15165771
TI  - Eponymous surgeon: Who and what was Mikulicz?

PMID- 15165773
TI  - Competent patient care is dependent upon attending to empathic opportunities
      presented during interview sessions.
AB  - OBJECTIVE: Core competencies in surgical education and clinical care rely on
      effective patient-physician communication. We aim to develop quantitative and
      empirical tools for understanding critical communication tasks during patient
      interviews. METHODS: Residents in surgical training and attending physicians were
      separately video recorded during stressful, first visit oncology patient
      interview sessions. Taped sessions (n = 16) were analyzed in detail to identify
      and label patient-initiated actions (PIAs), or "empathic opportunities," that
      call for recognition or action from the caregiver. Doctor-responsive actions
      (DRAs) were labeled as matching to, or missing from, each empathic opportunity.
      Missed empathic opportunities occurred when a PIA did not have an associated DRA.
      Presession and postsession surveys queried the patient's perception of how well
      their health-care needs were met. RESULTS: Resident trainees and attending
      physicians missed 70% of 160 clearly identified empathic opportunities. There was
      no clear association with the level of physician training. This pilot study did
      not have enough power to discern differences in patient satisfaction.
      CONCLUSIONS: Physicians are often not very attentive to empathic opportunities
      offered by patients. Individual feedback and training regarding empathic
      opportunities in recorded patient communication encounters may improve resident
      and physician core competencies. These improvements may affect patient
      satisfaction related to these encounters.

PMID- 15165772
TI  - A randomized study between excision and marsupialization and radiofrequency sinus
      excision in sacro-coccygeal pilonidal disease.
AB  - BACKGROUND: The surgical approach to pilonidal sinus disease is open to debate.
      This prospective, randomized study was aimed to compare the outcome of the
      excision and marsupialization and the sinus excision technique by radiofrequency.
      MATERIALS AND METHODS: Thirty patients of chronic pilonidal sinus disease were
      randomly assigned to radiofrequency sinus excision (n = 15) and excision and
      marsupialization (n = 15). The parameters measured included intraoperative and
      postoperative data, wound-related complications, and recurrence. Patient
      satisfaction score was assessed at 1-year follow-up. RESULTS: The operation time,
      postoperative pain, hospital stay, and off work periods were significantly less
      (p < 0.05) in the technique employing radiofrequency surgery. At 1-year follow
      up, there was 1 case of recurrence in each group. The patients from
      radiofrequency group expressed better satisfaction than the patients operated by
      marsupialization. CONCLUSION: Radiofrequency sinus excision technique needs a
      shorter hospital stay with reduced postoperative pain and early resumption to
      work in comparison with the sinus excision and marsupialization technique.

PMID- 15165774
TI  - Galactocele of the breast in a postmenopausal woman.

PMID- 15165775
TI  - Mechanical bowel preparation in the older surgical patient.
AB  - A major risk of colon resection is contamination from the bowel. Poor cleansing
      of the colon has been associated with an increased incidence of wound infections
      and intra-abdominal abscesses. Despite controversy on the usefulness of colon
      cleansing methods, mechanical bowel preparation along with oral and intravenous
      antibiotics have become common preoperative practice. The population is aging,
      and surgeons and endoscopists are going to be increasingly involved in the care
      of older patients. This review focuses on various colon cleansing methods and
      examines specific issues in older patients.

PMID- 15165776
TI  - Mentorship in academic medicine: a critical component for all faculty and
      academic advancement.

PMID- 15165777
TI  - Single pancreatic metastasis from a previously resected carcinoma of the cecum: a
      case report.
AB  - OBJECTIVE: To report a case of an isolated pancreatic metastasis from a primary
      cecum carcinoma. BACKGROUND: Carcinoma of the colon and rectum commonly
      metastasizes to distant sites such as liver, lung, bone, brain, and ovaries. Only
      a few cases of pancreatic metastasis from a primary colonic carcinoma had been
      reported. Metastasic lesions to the pancreas are found only in 3% to 12% of
      autopsies from advanced malignancies. Primary tumors that commonly metastasize to
      the pancreas are lung and kidney. Most of the patients with metastatic lesions to
      pancreas also had extrapancreatic metastatic disease. CASE: We report a case of a
      86-year-old woman with a single pancreatic metastasis from a primary cecum
      carcinoma resected 8 months before. CONCLUSIONS: The finding of an isolated
      metastasis to the pancreatic body from a primary cecum adenocarcinoma is
      extremely rare.

PMID- 15165778
TI  - Reflection on race and culture on the wards.

PMID- 15165781
TI  - An institution par excellence: Prof. B. Ramamurthi 1922-2003.

PMID- 15165782
TI  - Adopting 540-degree fusion to correct cervical kyphosis.
AB  - BACKGROUND: Two cases of severe cervical spine kyphotic deformity resulting from
      late effects of infection were successfully corrected by combined anterior and
      posterior instrumentations in a single operative sitting. CASE DESCRIPTION: Case
      1 is a 43-year-old man who developed severe cervical kyphosis from C5-6 discitis
      over a few months despite long-term antibiotic therapy. He was neurologically
      intact except for severe neck pain and obvious deformity. Case 2 is a 40-year-old
      woman who had a previous wound infection five years before presentation. There
      was gradual worsening of swan neck deformity at the C2-3 and C5-6 levels with
      some spinal cord compression worsening her baseline myelopathy. The patients were
      placed and maintained in cervical traction on the Stryker frame for the duration
      of the procedure. Both cases required anterior approach initially to achieve some
      release of dense scar tissue using a high-speed drill. The wounds were then
      closed and patients were rotated to the prone position for further release of
      fused bony elements, including the facets. Lateral mass screws and plates were
      placed. In Case 2, additional instrument to the occipital was performed to
      stabilize the C2 using a U-shaped cervical rod. Once adequate reduction had been
      achieved, the patients were rotated back to supine position for further
      corpectomy and fibular construct fusion with plates. CONCLUSION: In cases of
      severe kyphotic deformity complicating infectious vertebral destruction, the
      spinal alignment can be achieved safely by a multi-step technique combining the
      anterior as well as posterior surgical approaches.

PMID- 15165784
TI  - Various surgical treatments of chronic subdural hematoma and outcome in 172
      patients: is membranectomy necessary?
AB  - BACKGROUND: The initial surgical management of chronic subdural hematoma (CSDH)
      is still controversial, and a standard therapy does not exist. Because of the
      advanced age and multiple medical problems of the patients, surgical therapy is
      frequently associated with complications. METHODS: A retrospective study was
      performed on 172 patients with CSDH, comparing the efficacy of three different
      primary surgical methods: drainage of hematoma through two different burr-holes
      without membranectomy (Group A, n = 38); enlarged craniectomy with a size of
      about 30 mm craniotomy with partial membranectomy and drainage (Group B, n =
      121); and extended craniotomy with partial membranectomy and drainage (Group C, n
      = 13). RESULTS: Independent of surgical method, the general outcome of the
      patients was good. The rate of reoperation in the group of burr-hole drainage was
      16%, slightly lower than in partial membranectomy with enlarged craniectomy or
      extended craniotomy with 18% and 23%, respectively. In patients with
      coagulopathy, the rate of reoperation was 41% (16/43), significantly higher than
      the rate in noncoagulopathic patients 12% (15/129). CONCLUSIONS: In this study,
      an extended surgical approach with partial membranectomy has no advantages
      regarding the rate of reoperation and the outcome. As initial treatment, burr
      hole drainage with irrigation of the hematoma cavity and closed-system drainage
      is recommended. Extended craniotomy with membranectomy is now reserved for
      instances of acute rebleeding with solid hematoma.

PMID- 15165787
TI  - Gamma knife radiosurgery for trigeminal neuralgia: a study of predictors of
      success, efficacy, safety, and outcome at LSUHSC.
AB  - BACKGROUND: Trigeminal neuralgia (TN) is a painful condition of controversial
      origin; however, vascular compression of the root entry zone of the trigeminal
      nerve is thought to be responsible in some cases. Recently, stereotactic
      radiosurgery has been established as an alternative treatment for medically
      intractable TN. METHODS: Forty patients with medically refractory TN underwent
      gamma knife surgery for pain control at our institution. Dose planning was based
      on high-resolution, contrast-enhanced, axial, volume acquisition magnetic
      resonance images. Images were reviewed to detect vascular compression of the
      trigeminal nerve at the root entry zone by an observer blinded to the affected
      side and the outcome. Another observer, blinded to radiologic findings, conducted
      the patient follow-up. Results were classified as excellent and good (favorable
      outcomes) and failure (unfavorable) based upon the intensity of pain, frequency
      of episodes, pain medications, and need for additional interventions after
      radiosurgery. RESULTS: Pain was left-sided in 22 patients and right-sided in 18
      patients. Vascular compression of the affected nerve at the root entry zone was
      demonstrable in 14 patients. Prescription dose ranged from 70 to 90 Gy. At a
      median follow-up of 14 months (range, 3-31 months), 16 patients (40%) had
      excellent pain control, 12 (30%) had good control, while 12 (30%) had failed
      treatment. The Kaplan-Meier actuarial pain control rate at 15 months was 82.25 +/
      0.8% (95%CI). Magnetic resonance detectable vascular compression did not affect
      the outcome (p = 0.6). Increasing marginal dose (> or =40Gy) was a significant
      predictor of favorable outcome (p = 0.015). CONCLUSIONS: gamma knife surgery is
      an effective and safe treatment for TN. In our study, we found that vascular
      compression of the nerve at the root entry zone was not a predictor of the
      outcome of gamma surgery for TN. The outcome improves with marginal prescription
      dose of 80 Gy or higher.

PMID- 15165790
TI  - Autopsy findings of a craniopharyngioma with a natural course over 60 years.
AB  - BACKGROUND: We report the histologic manifestations in an autopsy case of
      craniopharyngioma with an unusually long treatment-free course. CASE DESCRIPTION:
      A 72-year-old woman with craniopharyngioma, in whom ateliosis due to the
      suprasellar tumor had been identified at the age of 10 years but had not been
      treated, was studied postmortem. She had not acquired secondary sex
      characteristics. At autopsy, a hard mass 2 cm in diameter was present in the
      suprasellar region and invaded the anterior floor of the third ventricle.
      Histologically, a large proportion of the mass was replaced by wet keratin,
      ossified tissue, dystrophic calcification, and fatty adipose tissue: these
      features indicate widespread degeneration of the tumor cells. Only a few residual
      cell nests of craniopharyngioma-composed of squamous cells lined with a single
      columnar cell layer-were observed at the peripheral portion of the mass.
      Conspicuous reactive astrocytosis with relatively high cellularity was evident in
      the brain tissue adjacent to the mass. CONCLUSION: This case may represent a rare
      example of craniopharyngioma lacking spontaneous growth activity and consequently
      showing marked degeneration of the tumor cells.

PMID- 15165792
TI  - A comparison of risk factors in the etiology of mirror and nonmirror multiple
      intracranial aneurysms.
AB  - BACKGROUND: Pure mirror intracranial aneurysms represent a subgroup of multiple
      aneurysm patients where a congenital predisposition may play a major etiologic
      role. The aim of this study was to compare the pattern of prevalence of known
      risk factors for aneurysm disease between pure mirror and pure nonmirror multiple
      aneurysm populations. METHODS: Clinical records of all patients with multiple
      intracranial aneurysms admitted to our institution between January 1985 and
      September 2001 were reviewed. Age, localization of aneurysms, gender, and history
      of cigarette smoking or hypertension were noted and compared using Fisher's exact
      test and logistic regression analysis. RESULTS: There were 33 patients presented
      with pure mirror aneurysms (MirAn) and 49 with nonmirror multiple aneurysms
      (nMirAn). Average age of rupture occurred in the 5th decade in both groups.
      Female:male ratio was 3.1:1 in MirAn; 2.1:1 in nMirAn. In MirAn patients younger
      than 40 years it was 1:1. Smoking was the most prevalent risk factor in nMirAn
      (59.2%). In MirAn this was true only for patients in the 5th or 6th decades
      (65%), and hypertension was the most prevalent risk factor over that age (62.5%).
      A total of 80% of mirror aneurysm patients under 40 years had no known extrinsic
      risk factor, compared with 20% in nMirAn (p < 0.05). CONCLUSIONS: Differences in
      the relative prevalence of risk factors between both groups supports the
      hypothesis of a different etiologic process occurring in mirror aneurysm disease.
      Early rupture in patients with no extrinsic risk factors lends support to the
      role of a congenital predisposition over degenerative causes in these patients.

PMID- 15165793
TI  - Surgery for carotid dural ring aneurysms.
AB  - BACKGROUND: Carotid aneurysms of the paraclinoid segment are usually located in
      the intradural space, but can infrequently straddle the intra- and extradural
      space. CASE DESCRIPTION: We present 2 cases of unruptured carotid dural ring
      aneurysms with an aneurysmal sac that straddled the distal dural ring. Each
      paraclinoid aneurysm projected superiorly from the anterior surface of the
      internal carotid artery with a relatively flattened dome and central indentation
      on angiography. The aneurysmal domes were circumscribed by the distal dural ring
      and straddled the intra- and extradural space. After broad opening of the distal
      dural ring, aneurysms were successfully obliterated by clip application in
      parallel with the internal carotid artery. CONCLUSION: These cases underscore the
      significance of an aneurysmal dome indentation on angiographic images as a
      reflection of aneurysmal circumscription by the distal dural ring. Aneurysms that
      straddle the intra- and extradural space may require broad opening of the distal
      dural ring for adequate control and clipping.

PMID- 15165794
TI  - Spinal Aspergillus vertebral osteomyelitis with extradural abscess: case report
      and review of literature.
AB  - BACKGROUND: Spinal extradural abscesses caused by Aspergillus species are rare
      and occur mostly in immunocompromised patients or in patients with Aspergillomas
      elsewhere in the body. In this report, the authors draw attention to a rapidly
      developing syndrome of extradural compressive myelopathy in an immunocompetent
      patient. Only four other cases have been reported previously. CASE DESCRIPTION: A
      35-year-old female presented with rapidly progressive painful paraparesis
      progressing to paraplegia in 15 days despite adequate empiric antitubercular
      therapy. Magnetic resonance imaging (MRI) revealed D11 vertebral body destruction
      and an extradural mass compressing the cord from D10 to D12. The patient
      underwent a D11 corpectomy and spinal stabilization with an iliac bone strut
      graft, 'Z' Plate and screw fixation. The biopsy showed fungal hyphae with
      dichotomous branching diagnostic of Aspergillosis. Despite treatment with
      Amphotericin B and oral Itraconazole the patient developed rapidly progressive
      multiorgan failure and expired after 2 months. CONCLUSIONS: The authors report
      the fifth and extremely rare case of Aspergillus vertebral osteomyelitis with an
      extradural abscess in an immunocompetent patient. Therapy is controversial and
      predicated on the use of highly toxic drugs with inconsistent efficacies.
      Mortality remains grievously high.

PMID- 15165796
TI  - Split cord malformation with neurenteric cyst and pregnancy.

PMID- 15165800
TI  - The trigeminal nerve and ganglion: an anatomical, histological, and radiological
      study addressing the transtrigeminal approach.
AB  - BACKGROUND: The transtrigeminal route with splitting of the trigeminal ganglion
      (TG) is a skull base approach used to expose the posteromedial part of the
      cavernous sinus (CS), the base of the TG, and the petrolingual ligament (PLL).
      METHODS: To verify the transtrigeminal approach (TTA), the 3 divisions of the
      trigeminal nerve (TN), the so-called TG, and the trigeminal root were analyzed
      anatomically, histologically, and radiologically. The anatomic study was
      performed bilaterally in 5 cadaveric head specimens. For the histologic study, 6
      TN specimens removed from cadavers were used. In addition, the radiologic
      demonstration of the TN and its so-called ganglion was performed on 5 cases by
      magnetic resonance imaging (MRI) scan. RESULTS: The TN is composed of linear,
      crossing, and connecting rootlets. These 3 types of rootlets indicate a plexiform
      constitution rather than a ganglion even though there are ganglionic cells.
      Consequently, the term "trigeminal plexus" may be preferred to describe this
      network. In our new proposed classification, the segments of the TN can be
      divided into 6 portions according to their relationship with the brainstem, the
      cisterns, and the bone structures. The first 3 segments before separating into 3
      divisions are (1) pontine, (2) cisternal (preganglionic or preplexal), (3)
      gasserian (ganglionic or plexal). The last 3 segments after the division are (4)
      preforamino-fissural (postganglionic or postplexal), (5) foramino-fissural, and
      (6) extracranial (postforamino-fissural). A loose connective tissue along the
      rootlets of the maxillary and the mandibular divisions of the TN at the gasserian
      (ganglionic or plexal) segment enabled us to split the so-called "trigeminal
      ganglion" or "gasserian ganglion" to perform the TTA. CONCLUSION: The TTA is
      possible, useful, and necessary in selected cases with invasion of the
      posteromedial part of the CS.

PMID- 15165798
TI  - Abducens schwannoma inside the cavernous sinus proper: case report.
AB  - BACKGROUND: Only 2 cases of abducens nerve schwannoma solely inside the cavernous
      sinus have been reported. In both cases, abducens nerve palsy remained after
      operation. We report the first case of abducens nerve schwannoma inside the
      cavernous sinus proper with postoperative recovery from abducens nerve palsy.
      CASE DESCRIPTION: The patient was a 47-year-old female who developed left
      abducens and trigeminal nerve palsies. Neuroradiological examination revealed
      left intra-cavernous sinus tumor. Total removal of the tumor was performed. The
      location of the tumor was confirmed intraoperatively inside the cavernous sinus
      itself, with no relation to the trigeminal nerve. Further, the relation of the
      tumor to one particular nerve fiber within the abducens nerve bundle was
      confirmed inside the cavernous sinus. After surgery, the patient had transient
      abducens nerve palsy. It had totally disappeared by 6 months. CONCLUSION: When
      the tumor origin is just within the spacious cavernous sinus rather than more
      posterior in the narrow dural tunnel of Dorello's canal, successful preservation
      of the nerve function is possible postoperatively through a thorough knowledge of
      the membranous anatomy and careful preoperative study of the radiographic
      findings.

PMID- 15165805
TI  - A syringe compressor for vertebroplasty: technical note.
AB  - OBJECTIVE: Percutaneous vertebroplasty (VP) has become a popular technique to
      treat osteoporotic vertebral compression fractures and spinal column neoplasms.
      The consistency of the bone cement mixture during the procedure would appear to
      be increasing with time, but the physician experiences injection difficulty, and
      there are also concerns with the limited injection time available for such a
      procedure. METHODS: We describe a special-design screw-syringe compressor to be
      used with the ordinary 10 mL Luer-Lok syringe and a short connecting tube for the
      injection of bone cement during VP. RESULTS: The syringe compressor could yield
      maximum 2,772 psi compression pressure and could finely control the cement
      delivery rate to 0.2 mL/ a turn. We have used this technique to treat 296
      consecutive patients with 384 vertebral compression fractures who were suffering
      from disabling back pain refractory to analgesic therapy. Using this technique,
      the injection time can be prolonged to 12 min and the delivery volume can be
      better controlled. CONCLUSION: With the aid of the syringe compressor, the
      cementing material can be accurately and steadily injected as desired by the
      physician. Bone-cement injection can be better controlled with this syringe
      compressor. Furthermore, this delivery system would reduce per treatment cost.

PMID- 15165804
TI  - Primary angiosarcoma of the cranial vault: a case report and review of the
      literature.
AB  - BACKGROUND: Angiosarcoma is a rare neoplasm. It is most likely to affect the
      scalp in elderly people and involvement of the cranium is uncommon. We report a
      case of primary malignant angiosarcoma of the cranial vault. CASE DESCRIPTION: An
      82-year-old man presented with right hemiparesis, deformity of the cranium and
      mildly swollen scalp. Further studies disclosed bilateral parietal lesions, with
      destruction of the dura matter and infiltration of the brain parenchyma.
      Thrombocytopenia was found. Faint enhancement of the lesions was seen on magnetic
      resonance imaging (MRI) after i.v. administration of contrast medium with
      gadolinium. The tumor was excised including the affected portion of the skull and
      dura matter. Histologic examination revealed typical pictures of angiosarcoma
      with immunohistochemical evidence of factor VIII-related antigen. Postoperative
      radiotherapy was employed. The patient remained well at 10 months postoperative
      follow up. CONCLUSION: Primary angiosarcoma of the cranium is sometimes difficult
      to differentiate from trauma on clinical examination. We review the literature
      pertaining to the pathogenesis, clinical course and treatment of this condition.
      Determination of platelet count may be helpful in monitoring the progression of
      the disease. The tumor may show faint enhancement on MRI.

PMID- 15165806
TI  - Gamma probe localization of cranial bone lesions: technical note.
AB  - BACKGROUND: Intraoperative localization of cranial bone lesions may be
      challenging especially when the lesion is not well demonstrated on computed
      tomography (CT) scan but solely on a radio-isotope bone scan. We hereby
      demonstrate a technique for localizing such lesions using an intraoperative gamma
      probe reader and summarize the relevant literature. METHODS: A case report of a
      temporal osteoid osteoma causing local pain and unresponsive to conservative
      treatment is presented. The lesion was demonstrated preoperatively solely on a
      bone scan, and was intra-operatively localized by a gamma probe reader. RESULTS:
      The lesion was totally excised with normal background readings after lesion
      removal. Six months after total removal of the osteoid osteoma, the patient is
      asymptomatic. CONCLUSION: Intraoperative gamma probe reader is a simple,
      effective, and safe method for intra-operative localization of bone lesions,
      which are positive on bone scans. It is especially useful for skull lesions that
      are not demonstrated by other imaging methods.

PMID- 15165807
TI  - An example of how to change what you are doing and like it.

PMID- 15165808
TI  - Health care issues in Taiwan: a parallel of worldwide circumstance.

PMID- 15165809
TI  - Re: Medical liability tort reform: a neurosurgeon's perspective. Surg Neurol
      2004;61:304-7.

PMID- 15165810
TI  - Re: medical liability tort reform: a neurosurgeon's perspective. Surg Neurol
      2004;61:304-7.

PMID- 15165812
TI  - Re: Medical professional liability. Surg Neurol 2004;61:26-28.

PMID- 15165813
TI  - Re: Injury, pseudo injury, and litigation. Surg Neurol 2003;60:478-482.

PMID- 15165814
TI  - Is there enough gp120 in the body fluids of HIV-1-infected individuals to have
      biologically significant effects?

PMID- 15165815
TI  - Analysis of thermal stress-mediated PSTVd variation and biolistic inoculation of
      progeny of viroid "thermomutants" to tomato and Brassica species.
AB  - Thermal stress of PSTVd-infected Nicotiana benthamiana led to appearance of a
      broad PSTVd sequence distribution, where most of mutations accumulated in the
      left half of the viroid's secondary structure including the "pathogenicity"
      domain. A similar effect had been reported for hop latent viroid [Virology 287
      (2001) 349]. The pool of viroid "thermomutants" progenies was transcribed into
      cDNA and used for biolistic inoculation of Raphanus sativa, where the PSTVd
      infection was detectable by reverse transcription and polymerase chain reaction
      (RT-PCR). Newly generated inoculum from R. sativa was used for biolistic transfer
      to Arabidopsis thaliana wild-type and silencing-deficient mutants bearing one of
      sde1, sde2, and sde3 locuses. Irrespective to A. thaliana silencing mutants,
      viroid levels in Brasicaceae species infected with mutated PSTVd variants were of
      approximately 300 times lower than it is expected for tomato. At the same time,
      no systemic infection of A. thaliana was achieved with the wild-type PSTVd. In
      Arabidopsis, a population of PSTVd, consisting of frequent and minor variants,
      was present and the sequence distribution differed from that of the original
      viroid "thermomutants"; that is, mutations were not predominantly restricted to
      the left half of viroid's secondary structure. At least 65% of viroid sequences
      from Arabidopsis library accumulated mutations in the upper conserved central
      region (UCCR). In addition, mutants having changes in "hairpin II" domain (C-->A
      transition at position 229) and in the conserved internal loop element in the
      left part of viroid structure (single insertion of G at position 39) were
      detected. All those mutants were inoculated biolistically to tomato and promoted
      infection especially after prolonged period of plant cultivation (50-80 days pi)
      when infection reached 70-90%. However, the sequence variants were unstable and
      reverted to the wild type and to other sequence variants stable in tomato. Our
      results demonstrate that heat stress-mediated production of viroid quasi-species
      could be of significance for viroid adaptations.

PMID- 15165816
TI  - Interspecies transmission of an H7N3 influenza virus from wild birds to
      intensively reared domestic poultry in Italy.
AB  - Since the "bird flu" incident in Hong Kong SAR in 1997, several studies have
      highlighted the substantial role of domestic birds, such as turkeys and chickens,
      in the ecology of influenza A viruses. Even if recent evidence suggests that
      chickens can maintain several influenza serotypes, avian influenza viruses (AIVs)
      circulating in domestic species are believed to be introduced each time from the
      wild bird reservoir. However, so far the direct precursor of influenza viruses
      from domestic birds has never been identified. In this report, we describe the
      antigenic and genetic characterization of the surface proteins of H7N3 viruses
      isolated from wild ducks in Italy in 2001 in comparison to H7N3 strains that
      circulated in Italian turkeys in 2002-2003. The wild and domestic avian strains
      appeared strictly related at both phenotypic and genetic level: homology
      percentages in seven of their genes were comprised between 99.8% (for PB2) and
      99.1% (for M), and their NA genes differed mainly because of a 23-aminoacid
      deletion in the NA stalk. Outside this region of the molecule, the NAs of the two
      virus groups showed 99% similarity. These findings indicate that turkey H7N3
      viruses were derived "in toto" from avian influenza strains circulating in wild
      waterfowl 1 year earlier, and represent an important step towards the
      comprehension of the mechanisms leading to interspecies transmission and
      emergence of potentially pandemic influenza viruses.

PMID- 15165818
TI  - The multifunctional plant viral suppressor of gene silencing P19 interacts with
      itself and an RNA binding host protein.
AB  - Tomato bushy stunt virus (TBSV) is an RNA plant virus encoding a protein of
      approximately 19 kDa (P19) that is involved in various activities important for
      pathogenicity, including virus transport and suppression of gene silencing. In
      this study, we provide evidence in vivo and in vitro that P19 specifically
      interacts with itself to predominantly form dimers, and with a novel host
      protein, Hin19. Hin19 has a high degree of similarity with a class of RNA-binding
      proteins of which many are involved in RNA processing. The binding of P19 to
      itself and to Hin19 both depend on a structurally important central region of P19
      that was previously shown critical for its biological function in plants. Our
      findings provide evidence for a model in which virus spread through suppression
      of defense-related gene silencing involves the formation of a complex that
      includes P19 dimers and a newly identified host RNA-binding protein.

PMID- 15165817
TI  - Cowpea mosaic virus RNA-1 acts as an amplicon whose effects can be counteracted
      by a RNA-2-encoded suppressor of silencing.
AB  - Lines of Nicotiana benthamiana transgenic for full-length copies of both Cowpea
      mosaic virus (CPMV) genomic RNAs, either singly or together, have been produced.
      Plants transgenic for both RNAs developed symptoms characteristic of a CPMV
      infection. When plants transgenic for RNA-1 were agro-inoculated with RNA-2, no
      infection developed and the plants were also resistant to challenge with CPMV. By
      contrast, plants transgenic for RNA-2 became infected when agro-inoculated with
      RNA-1 and were fully susceptible to CPMV infection. The resistance of RNA-1
      transgenic plants was shown to be related to the ability of RNA-1 to self
      replicate and act as an amplicon. The ability of transgenically expressed RNA-2
      to counteract the amplicon effect suggested that it encodes a suppressor of
      posttranscriptional gene silencing (PTGS). By examining the ability of portions
      of RNA-2 to reverse PTGS in N. benthamiana, we have identified the small (S) coat
      protein as the CPMV RNA-2-encoded suppressor of PTGS.

PMID- 15165819
TI  - Role of bovine adenovirus-3 33K protein in viral replication.
AB  - The L6 region of bovine adenovirus type (BAdV)-3 encodes a nonstructural protein
      named 33K. To identify and characterize the 33K protein, rabbit polyclonal
      antiserum was raised against a 33K-GST fusion protein expressed in bacteria. Anti
      33K serum immunoprecipitated a protein of 42 kDa in in vitro translated and
      transcribed mRNA of 33K. However, three proteins of 42, 38, and 33 kDa were
      detected in BAdV-3 infected cells. To determine the role of this protein in virus
      replication, a recombinant BAV-33S1 containing insertional inactivation of 33K (a
      stop codon created at the seventh amino acid of 33K ORF) was constructed.
      Although BAV-33S1 could be isolated, the mutant showed a severe defect in the
      production of progeny virus. Inactivation of the 33K gene showed no effect on
      early and late viral gene expression in cells infected with BAV-33S1. However,
      formation of mature virions was significantly reduced in cells infected with BAV
      33S1. Surprisingly, insertional inactivation of 33K at amino acid 97 (pFBAV
      33.KS2) proved lethal for virus production. Although expression of early or late
      genes was not affected, no capsid formation could be observed in mutant DNA
      transfected cells. These results suggest that 33K is required for capsid assembly
      and efficient DNA capsid interaction.

PMID- 15165820
TI  - Comparative genomic analyses of frog virus 3, type species of the genus Ranavirus
      (family Iridoviridae).
AB  - Frog virus 3 (FV3) is the type species member of the genus Ranavirus (family
      Iridoviridae). To better understand the molecular mechanisms involved in the
      replication of FV3, including transcription of its highly methylated DNA genome,
      we have determined the complete nucleotide sequence of the FV3 genome. The FV3
      genome is 105903 bp long excluding the terminal redundancy. The G + C content of
      FV3 genome is 55% and it encodes 98 nonoverlapping potential open reading frames
      (ORFs) containing 50-1293 amino acids. Eighty-four ORFs have significant homology
      to known proteins of other iridoviruses, whereas twelve of these unique FV3
      proteins do not share homology to any known protein. A microsatellite containing
      a stretch of 34 tandemly repeated CA dinucleotide in a noncoding region was
      detected. To date, no such sequence has been reported in any animal virus.

PMID- 15165821
TI  - Varicella-Zoster virus proteins encoded by open reading frames 14 and 67 are both
      dispensable for the establishment of latency in a rat model.
AB  - A rat model of Varicella-Zoster virus (VZV) provides a system in which to
      investigate the molecular determinants of viral latency in dorsal root ganglia
      (DRG). In this study, we determined whether the VZV glycoproteins gC and gI,
      corresponding to VZV open reading frames (ORFs) 14 and 67, respectively, were
      required for the establishment of latency in this model. A VZV gI deletion mutant
      (DeltagI) derived from a recombinant Oka (rOka) cosmid and a gC null mutant
      obtained from a clinical isolate were inoculated into the footpads of 6-week-old
      rats, and the presence of viral DNA and eight different VZV RNA transcripts
      corresponding to the three classes of genes was investigated by in situ RT-PCR
      amplification and in situ hybridization (ISH) in the DRG at 1 week, 1 month, and
      18-24 months after infection. VZV DNA and restricted RNA expression was
      established with both deletion mutants as well as the parental rOka virus. Both
      VZV DNA and RNA were detected in neurons and non-neuronal cells. The pattern of
      viral RNA expression detected with both gC and gI mutants was restricted with
      transcripts for VZV genes 62 and 63 most frequently expressed 18-24 months after
      infection. Transcripts for VZV genes 18, 28, and 29 were also detected at these
      time points but at a slightly lower frequency. Transcripts for the late gene 40
      were never detected. We conclude that VZV ORFs 14 and 67 are dispensable for the
      establishment of a latent infection in this model.

PMID- 15165822
TI  - Fusion of the upstream vpu sequences to the env of simian human immunodeficiency
      virus (SHIV(KU-1bMC33)) results in the synthesis of two envelope precursor
      proteins, increased numbers of virus particles associated with the cell surface
      and is pathogenic for pig-tailed macaques.
AB  - Previous studies have shown that the gene coding for the Vpu protein of the human
      immunodeficiency virus type 1 (HIV-1) is 5' to the env gene, is in a different
      reading frame, and overlaps the env by 90 nucleotides. In this study, we examined
      the processing of the Env protein as well as the maturation and infectivity of a
      virus (SHIV(Vpenv)) in which a single nucleotide was removed at the vpu-env
      junction, fusing the first 162 bases of vpu to the env ORF. Pulse-chase analysis
      revealed that SHIV(Vpenv)-infected cells gave rise to two precursor glycoprotein
      species (gp160 and gp175). Immune precipitation results also revealed that an
      anti-Vpu serum could immune precipitate the gp175 precursor, suggesting that the
      amino-terminal Vpu sequence was fused to the Env protein. Growth curves revealed
      that the SHIV(Vpenv)-inoculated cultures released approximately three times more
      p27 into the culture medium than parental SHIV(KU-1bMC33). Electron microscopy
      revealed that while both viruses matured at the cell plasma membrane,
      significantly higher quantities of virus particles were cell associated on
      SHIV(Vpenv)-infected cells compared to cultures inoculated with parental SHIV(KU
      1bMC33). Furthermore, virus was observed maturing into intracellular vesicles of
      SHIV(Vpenv)-infected cells. To assess the pathogenicity of SHIV(Vpenv), three pig
      tailed macaques were inoculated with the SHIV(Vpenv) and monitored for 6 months
      for CD4(+) T cell levels, viral loads, and the stability of the deletion at the
      vpu-env junction. Our results indicated that SHIV(Vpenv) caused a severe CD4(+) T
      cell loss in all three macaques within weeks of inoculation. Sequence analysis of
      the vpu gene analyzed from sequential PBMC samples derived from macaques revealed
      that this mutation was stable during the period of rapid CD4(+) T cell loss.
      Sequence analysis showed that with increasing time of infection, the one base
      pair deletion was repaired in all three macaques inoculated with SHIV(Vpenv) with
      the reversion occurring at 10 weeks in macaque CT1G and at 12 weeks in macaque
      CP3R and CT1R. These results indicate that fusion of the first 54 amino acids of
      Vpu to Env results in intracellular maturation of virus, and accumulation of
      virus within intracellular vesicles as well as on the cell plasma membrane. Our
      results indicate that while fusion of the vpu gene to env results in a virus that
      is still pathogenic for pig-tailed macaques, there is a selective pressure to
      maintain the vpu and env genes in separate reading frames.

PMID- 15165823
TI  - An amino-terminal segment of hantavirus nucleocapsid protein presented on
      hepatitis B virus core particles induces a strong and highly cross-reactive
      antibody response in mice.
AB  - Previously, we have demonstrated that hepatitis B virus (HBV) core particles
      tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala
      hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of
      120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan
      hantaviruses allows the formation of chimeric core particles. These particles
      expose the inserted foreign protein segments, at least in part, on their surface.
      Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala
      virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed
      from T = 3 shells shows additional density splaying out from the tips of the
      spikes producing the effect of an extra shell of density at an outer radius
      compared with wild-type shells. The inserted Puumala virus N protein segment is
      flexibly linked to the core spikes and only partially icosahedrally ordered.
      Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with
      chimeric core particles induces a high-titered and highly cross-reactive N
      specific antibody response in both mice strains.

PMID- 15165824
TI  - Role of AcMNPV IE0 in baculovirus very late gene activation.
AB  - IE0 is the only known baculovirus protein that is produced by splicing. In this
      study, we have explored the role of Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) IE0 and its interaction with IE1 in the activation
      of very late gene expression from the polyhedrin promoter using transient assays.
      IE0 is co-expressed with IE1 throughout infection up to late times post-infection
      (p.i.) but shows peak levels of expression at early times. Significant changes in
      the ratios of the relative levels of IE0 to IE1 were observed throughout the
      course of infection. To study IE0 in the absence of IE1, we constructed a plasmid
      pAc-IE0(M-->A) that expressed only IE0. This was due to a mutation of the
      internal AUG that prevented translation of IE1 from the ie0 mRNA. Both IE0 and
      IE0(M-->A) were able to replace IE1 in transient assays, showing that IE0 is
      functional for very late gene activation and should be considered the 20th late
      gene expression factor (lef). In transient assays, IE0 showed that maximum very
      late gene expression is achieved at very low relative levels of protein. In
      contrast, IE1 requires higher levels of protein to obtain maximum very late gene
      expression. Furthermore, when the levels of IE0 become too high, very late gene
      expression rapidly declines. Interestingly, co-expression of IE0 and IE1 results
      in a mutually antagonistic affect on very late gene expression.

PMID- 15165825
TI  - cis-Acting and trans-acting modulation of equine infectious anemia virus
      alternative RNA splicing.
AB  - Equine infectious anemia virus (EIAV), a lentivirus distantly related to HIV-1,
      encodes regulatory proteins, EIAV Tat (ETat) and Rev (ERev), from a four-exon
      mRNA. Exon 3 of the tat/rev mRNA contains a 30-nucleotide purine-rich element
      (PRE) which binds both ERev and SF2/ASF, a member of the SR family of RNA
      splicing factors. To better understand the role of this element in the regulation
      of EIAV pre-mRNA splicing, we quantified the effects of mutation or deletion of
      the PRE on exon 3 splicing in vitro and on alternative splicing in vivo. We also
      determined the branch point elements upstream of exons 3 and 4. In vitro splicing
      of exon 3 to exon 4 was not affected by mutation of the PRE, and addition of
      purified SR proteins enhanced splicing independently of the PRE. In vitro
      splicing of exon 2 to exon 3 was dependent on the PRE; under conditions of excess
      SR proteins, either the PRE or the 5' splice site of exon 3 was sufficient to
      activate splicing. We applied isoform-specific primers in real-time RT-PCR
      reactions to quantitatively analyze alternative splicing in cells transfected
      with rev-minus EIAV provirus constructs. In the context of provirus with wild
      type exon 3, greater than 80% of the viral mRNAs were multiply spliced, and of
      these, less than 1% excluded exon 3. Deletion of the PRE resulted in a decrease
      in the relative amount of multiply spliced mRNA to about 40% of the total and
      approximately 39% of the viral mRNA excluded exon 3. Ectopic expression of ERev
      caused a decrease in the relative amount of multiply spliced mRNA to
      approximately 50% of the total and increased mRNAs that excluded exon 3 to about
      4%. Over-expression of SF2/ASF in cells transfected with wild-type provirus
      constructs inhibited splicing but did not significantly alter exon 3 skipping.

PMID- 15165826
TI  - Multiple signal transducers and activators of transcription are induced by EBV
      LMP-1.
AB  - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) is required for EBV
      immortalization of primary B cells in vitro. Signal transducers and activators of
      transcription (STATs) play a pivotal role in the initiation and maintenance of
      certain cancers. STAT proteins, especially STAT-1, -3, and -5, are persistently
      tyrosine phosphorylated or activated in many cancers. We show here that EBV
      infected type III latency cells, in which the EBV oncoprotein, LMP-1 is
      expressed, express high levels of four STATs (STAT-1, -2, -3, and -5A) and that
      LMP-1 is responsible for the induction of three (STAT-1, -2, and -3). In
      addition, the C-terminal activator region 1 (CTAR-1) and CTAR-2 of LMP-1
      cooperatively induced the expression of STAT-1. The cooperativity was evident
      when CTAR-1 and CTAR-2 were present in cis, but not in trans. Furthermore, NF
      kappaB is an essential factor involved in the induction of STAT-1. Most of the
      induced STATs were not phosphorylated at the critical tyrosine residue activated
      by many cytokines. However, the induced STATs, at least STAT-1, were functional
      because it could be activated by interferon (IFN) and could upregulate an IFN
      inducible gene. Finally, expression of STAT-1, but not STAT-2 and -3, is
      associated with EBV transformation. The association of the expression of STAT-1, 
      2, -3, and -5A with EBV type III latency and the expression of STAT-1 in the EBV
      transformation process may be part of the viral programming that regulates viral
      latency and cellular transformation.

PMID- 15165828
TI  - Isolation and characterization of subgenomic DNAs encapsidated in "single" T = 1
      isometric particles of Maize streak virus.
AB  - "Single" T = 1 isometric particles of Maize streak virus (MSV) have been isolated
      from infected maize leaves. Biochemical and genetic characterizations show that
      these particles contain subgenomic (sg) MSV DNA encapsidated by the MSV coat
      protein. The largest sg DNA is 1.56 kb, slightly larger than half genome size,
      although sg DNAs as small as 0.2 kb were also cloned. The sg DNAs are not
      infectious, and they do not appear to play a role in the pathogenicity of MSV.
      This is the first report of sg DNAs for MSV and, to our knowledge, the first time
      that encapsidated sg DNAs have been characterized at the sequence level for any
      geminivirus. These data will assist in our investigations into the role of
      genomic DNA in the formation of the unique geminate capsid architecture of the
      Geminiviridae.

PMID- 15165827
TI  - Regulation of Semliki Forest virus RNA replication: a model for the control of
      alphavirus pathogenesis in invertebrate hosts.
AB  - Alphavirus nonstructural proteins are translated as a polyprotein that is
      ultimately cleaved into four mature proteins called nsP1, nsP2, nsP3, and nsP4
      from their order in the polyprotein. The role of this nonstructural polyprotein,
      of cleavage intermediates, and of mature proteins in synthesis of Semliki Forest
      virus (SFV) RNA has been studied using mutants unable to cleave one or more of
      the sites in the nonstructural polyprotein or that had the arginine sense codon
      between nsP3 and nsP4 changed to an opal termination codon. The results were
      compared with those obtained for Sindbis virus (SINV), which has a naturally
      occurring opal codon between nsP2 and nsP3. We found that (1) an active
      nonstructural protease in nsP2 is required for RNA synthesis. This protease is
      responsible for all three cleavages in the nonstructural polyprotein. (2)
      Cleavage between nsP3 and nsP4 (the viral RNA polymerase) is required for RNA
      synthesis by SFV. (3) SFV mutants that are able to produce only polyprotein P123
      and nsP4 synthesize minus-strand RNA early after infection as efficiently as SF
      wild type but are defective in the synthesis of plus-strand RNA. The presence of
      sense or opal following nsP3 did not affect this result. At 30 degrees C, they
      give rise to low yields of virus after a delay, but at 39 degrees C, they are
      nonviable. (4) SFV mutants that produce nsP1, P23, nsP4, as well as the precursor
      P123 are viable but produce an order of magnitude less virus than wild type at 30
      degrees C and two orders of magnitude less virus at 39 degrees C. The ratio of
      subgenomic mRNA to genomic RNA is much reduced in these mutants relative to the
      parental viruses. (5) At 30 degrees C, the variants containing an opal codon grow
      as well as or slightly better than the corresponding virus with a sense codon. At
      39 degrees C, however, the opal variants produce significantly more virus. These
      results support the conclusion that SFV and SINV, and by extension all
      alphaviruses, regulate their RNA synthesis in the same fashion after infection.
      P123 and nsP4 form a minus-strand replicase that synthesizes plus-strand RNA only
      inefficiently, especially at the higher temperatures found in mammals and birds.
      A replicase containing nsP1, P23, and nsP4 can make both plus and minus strands,
      but prefers the promoter for genomic plus sense RNA to that for subgenomic mRNA.
      The fully cleaved replicase can make only plus-strand RNA, and prefers the
      promoter for subgenomic mRNA to that for genomic RNA. Alphaviruses alternate
      between infection of hematophagous arthropods and higher vertebrates. Although
      the infection of higher vertebrates is acute and often accompanied by disease,
      continuing transmission of the virus in nature requires that infection of
      arthropods be persistent and relatively asymptomatic. We propose that this
      mechanism for control of RNA synthesis evolved to moderate the pathogenicity of
      the viruses in their arthropod hosts.

PMID- 15165829
TI  - Selective action of (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate
      (LY379268), a group II metabotropic glutamate receptor agonist, on basal and
      phencyclidine-induced dopamine release in the nucleus accumbens shell.
AB  - The effect of the group II metabotropic receptor agonist (-)-2-oxa-4
      aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), on basal and
      phencyclidine-induced dopamine efflux were measured in the shell and core
      subdivisions of the nucleus accumbens--regions which are associated with limbic
      and motor functions, respectively. Extracellular levels of dopamine were measured
      using microdialysis in conscious animals, and LY379268 was delivered locally by
      inclusion in the artificial cerebrospinal fluid (aCSF) flowing through the
      microdialysis probe. Local administration of LY379268 in the concentration range
      10 nM-10 microM reduced basal levels of dopamine in the nucleus accumbens shell,
      whilst having no effect in the nucleus accumbens core. In the nucleus accumbens
      shell, basal levels were reduced to approximately 60% compared to the pre
      injection control, with a maximal reduction occurring at concentrations of
      LY379268 > or =100 nM. The response to LY379268 (100 nM) was reversible, with
      levels returning to baseline following its removal from the aCSF. In a separate
      experiment, local perfusion of the nucleus accumbens shell with LY379268 (at both
      1 and 10 microM) reduced the magnitude of the response to a subsequent systemic
      administration of phencyclidine (5 mg/kg i.p.). The reduction in the peak
      dopamine response was only evident with doses of LY379268 that also reduced basal
      dopamine efflux--LY379268 being ineffective against PCP at 10 nM. However, in
      animals pre-treated with LY379268 at 1 or 10 microM, PCP still evoked a dopamine
      response, and in these animals the relative extent of the response was not
      significantly different between the respective treatment groups. In contrast, in
      the nucleus accumbens core the magnitude of the dopamine response to PCP was
      unaffected by local application of LY379268 (at 1 or 10 microM). Our data suggest
      that within the nucleus accumbens, there exists a distinct regional difference in
      the control of dopamine release by group II mGluRs, with the nucleus accumbens
      shell being preferentially affected. Moreover, the selective action of LY379268
      on dopamine levels in the nucleus accumbens shell may have implications for the
      potential antipsychotic activity of group II mGluR agonists.

PMID- 15165830
TI  - Ethanol administration rapidly reverses alpha4 GABAA receptor subunit
      upregulation following steroid exposure.
AB  - Both short-term (48 h) exposure to the neuroactive steroid 3alpha,5alpha[beta]
      THP and its withdrawal increase expression of the benzodiazepine (BDZ)
      insensitive GABAA receptor (GABAR) alpha4 subunit in hippocampus. This increase
      in alpha4 subunit expression was associated with a relative insensitivity of CA1
      hippocampal pyramidal cells to modulation of GABA-gated current by the BDZ
      lorazepam (LZM), assessed using whole cell patch clamp techniques. Chronic
      ethanol is also known to regulate expression of the alpha4 subunit. Thus, in the
      present study we investigated the capacity of ethanol, administered in low doses
      across a 2 h period (0.5 g/kg, i.p., 3x), to suppress alpha4 expression produced
      by 48 h exposure to 3alpha,5 beta-THP in adult female rats. We show here that 2 h
      ethanol administration reverses the increase in alpha4 expression normally
      observed following 48 h steroid treatment. This effect was correlated with a
      recovery of responses recorded from CA1 hippocampal pyramidal cells to the GABA
      modulatory effects of LZM. Similar effects of ethanol in suppressing alpha4
      expression and restoring LZM responsiveness were seen following steroid
      withdrawal when alpha4 expression is normally increased. These results suggest
      that increases in expression of the alpha4 subunit produced by steroid exposure
      or withdrawal are altered by other GABA-modulatory drugs, such as ethanol.

PMID- 15165831
TI  - Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA
      receptor gamma2 subunit.
AB  - Agonists of the allosteric benzodiazepine site of GABAA receptors bind at the
      interface of the alpha and gamma subunits. Here, we tested the in vivo
      contribution of the gamma2 subunit to the actions of zolpidem, an alpha1 subunit
      selective benzodiazepine agonist, by generating mice with a phenylalanine (F) to
      isoleucine (I) substitution at position 77 in the gamma2 subunit. The gamma2F77I
      mutation has no major effect on the expression of GABAA receptor subunits in the
      cerebellum. The potency of zolpidem, but not that of flurazepam, for the
      inhibition of [3H]flunitrazepam binding to cerebellar membranes is greatly
      reduced in gamma2I77/I77 mice. Zolpidem (1 microM) increased both the amplitude
      and decay of miniature inhibitory postsynaptic currents (mIPSCs) in Purkinje
      cells of control C57BL/6 (34% and 92%, respectively) and gamma2F77/F77 (20% and
      84%) mice, but not in those of gamma2F77I mice. Zolpidem tartrate had no effect
      on exploratory activity (staircase test) or motor performance (rotarod test) in
      gamma2I77/I77 mice at doses up to 30 mg/kg (i.p.) that strongly sedated or
      impaired the control mice. Flurazepam was equally effective in enhancing mIPSCs
      and disrupting performance in the rotarod test in control and gamma2I77/I77 mice.
      These results show that the effect of zolpidem, but not flurazepam, is
      selectively eliminated in the brain by the gamma2F77I point mutation.

PMID- 15165834
TI  - Nicotine exerts a permissive role on NMDA receptor function in hippocampal
      noradrenergic terminals.
AB  - The coexistence of nicotinic cholinergic receptors (nAChRs) and of N-methyl-D
      aspartate (NMDA) receptors on the same noradrenergic axon terminals and the
      nAChR/NMDA receptor cross-talk were investigated by monitoring the release of
      noradrenaline (NA) evoked in superfused rat hippocampal synaptosomes by (-)
      nicotine and NMDA alone or in combination. In medium containing a physiological
      concentration (1.2 mM) of Mg2+, the release of [3H]NA was very slightly increased
      by NMDA plus glycine, whereas it was significantly enhanced by (-)-nicotine. The
      (-)-nicotine/NMDA combination elicited supraadditive release which was totally
      abolished by the nAChR blocker mecamylamine and partly prevented by selectively
      blocking NMDA receptors. Supraadditive [3H]NA release was also observed by
      exposing synaptosomes to veratrine, but not to ionomycin. The supraadditive
      release elicited by the (-)-nicotine/NMDA or the veratrine/NMDA combination was
      sensitive to the protein kinase A/C inhibitor staurosporine and the selective
      protein kinase A inhibitor H89, but insensitive to the protein kinase C inhibitor
      Ro 31-8220. It is concluded that (i) release-modulating nAChRs and NMDA receptors
      coexist on hippocampal noradrenergic axon terminals; and (ii) nicotine permits
      NMDA receptor activation in the presence of Mg2+, possibly because the nicotine
      induced influx of Na+ depolarizes the nerve ending membrane sufficiently to
      remove the Mg2+ block.

PMID- 15165832
TI  - Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous
      rhythmic activity from the isolated neonatal rat respiratory network.
AB  - Acamprosate (calcium acetylhomotaurinate) has been shown to be effective in
      attenuating relapse in human alcoholics. The precise mechanism for acamprosate
      has been yet to be determined as there may be multiple sites of action for this
      drug. We investigated the mechanism of action of acamprosate on a spontaneous
      rhythmic activity recorded from hypoglossal nerve rootlet (XII) in neonatal rat
      brainstem slices. At 30 microM, acamprosate reversibly increased burst amplitude
      and reduced burst frequency, whereas at higher concentrations (100-400 microM) it
      induced a reversible and concentration-dependent inhibition of this activity.
      Interestingly, acamprosate (30 microM) enhanced the effects of low NMDA-induced
      excitation (1.5 microM), but inhibited higher NMDA-induced excitation (2.5, 5
      microM) by 50-70%, demonstrating a differential effect on NMDA-induced
      excitation. Blockade of GABAA receptors did not affect the increase in amplitude
      of 30 microM acamprosate and partially abolished the inhibitory effects of 200
      microM acamprosate. At 200 microM, acamprosate reduced high NMDA-induced
      excitation and abolished NMDA-evoked excitatory tonic phase, suggesting that
      excitatory effect of low concentrations of acamprosate mainly involved NMDA
      receptors, while the inhibitory effects at higher concentration included an
      increase in GABAA-mediated inhibition with a reduction of NMDA-mediated
      excitation. Consequently, combined blockade of both receptors abolished all
      effects of acamprosate tested at all concentrations. These results show that the
      effects of acamprosate are mediated via both GABAA and NMDA receptors and suggest
      a partial co-agonist role on NMDA receptors, at the level of a spontaneously
      active network.

PMID- 15165833
TI  - Characterisation of UBP296: a novel, potent and selective kainate receptor
      antagonist.
AB  - Willardiine derivatives with an N3-benzyl substituent bearing an acidic group
      have been synthesized with the aim of producing selective antagonists for GLUK5
      containing kainate receptors. UBP296 was found to be a potent and selective
      antagonist of native GLUK5-containing kainate receptors in the spinal cord, with
      activity residing in the S enantiomer (UBP302). In cells expressing human kainate
      receptor subunits, UBP296 selectively depressed glutamate-induced calcium influx
      in cells containing GLUK5 in homomeric or heteromeric forms. In radioligand
      displacement binding studies, the willardiine analogues displaced [3H]kainate
      binding with IC50 values >100 microM at rat GLUK6, GLUK2 or GLUK6/GLUK2. An
      explanation of the GLUK5 selectivity of UBP296 was obtained using homology models
      of the antagonist bound forms of GLUK5 and GLUK6. In rat hippocampal slices,
      UBP296 reversibly blocked ATPA-induced depressions of synaptic transmission at
      concentrations subthreshold for affecting AMPA receptor-mediated synaptic
      transmission directly. UBP296 also completely blocked the induction of mossy
      fibre LTP, in medium containing 2 mM (but not 4 mM) Ca2+. These data provide
      further evidence for a role for GLUK5-containing kainate receptors in mossy fibre
      LTP. In conclusion, UBP296 is the most potent and selective antagonist of GLUK5
      containing kainate receptors so far described.

PMID- 15165835
TI  - Rasagiline enhances L-DOPA-induced contralateral turning in the unilateral 6
      hydroxydopamine-lesioned guinea-pig.
AB  - The modification of L-3,4-dihydrooxyphenylalanine- (L-DOPA-) induced turning
      response by the new selective monoamine oxidase type B (MAO-B) inhibitor
      rasagiline was studied in guinea-pigs bearing a unilateral 6-hydroxydopamine
      induced lesion in the substantia nigra. In an initial experiment, it was
      established that contralateral turning is induced in lesioned guinea-pigs in
      response to apomorphine (18 mg/kg i.p.) and L-DOPA/carbidopa (15/3.5 mg/kg i.p.),
      while ipsilateral turning is induced by S(+)-methamphetamine (7 mg/kg i.p.). The
      effect of rasagiline was studied in a chronic treatment regimen, in which animals
      were treated with rasagiline (0.05 mg/kg s.c.) or saline s.c. daily commencing 2
      weeks after lesioning, and L-DOPA/carbidopa (4:1 mg/kg) was administered once
      daily for 21 days. Only guinea-pigs with 95% or more depletion of striatal
      dopamine were included in this study. Guinea-pigs treated with rasagiline had a
      significantly increased intensity and duration of turning in response to L-DOPA
      (P <0.05 by repeated measures ANOVA) over the 21-day period. On day 21, turning
      averaged 806+/-105 (n=10) vs 442+/-123 (n=11) turns per 180 min for rasagiline
      and vehicle treated animals, respectively (P <0.05); turning duration half-time
      averaged 81+/-15.4 (n=10) as opposed to 33+/-7.6 (n=11) min for rasagiline and
      vehicle treatments (P <0.01). Concentration of dopamine in intact striatum was
      significantly increased (69.3+/-2.1 and 60.3+/-2.4 pmol/mg tissue for rasagiline
      and vehicle, P <0.05) and levels of dihydroxyphenylacetic acid and homovanillic
      acid were decreased by the rasagiline treatment. Activity of brain MAO-B was
      8.6+/-2.9% and MAO-A was 71+/-1.5% that of control in rasagiline-treated animals.
      Chronic, selective inhibition of MAO-B by rasagiline potentiated L-DOPA-induced
      turning in this rodent model.

PMID- 15165837
TI  - Nitrergic and glutamatergic neuronal mechanisms at the trigeminovascular first
      order synapse.
AB  - Nitric oxide (NO) donors such as glyceryl trinitrate cause headache, which
      suggests involvement of NO in trigeminovascular sensory processing. Sensory
      transmission at first-order synapses is believed to involve glutamate and the
      question arises as to whether it is also involved in trigeminovascular sensation
      and whether it might interact with nitrergic mechanisms. We investigated these
      questions at the first central synapse in the trigeminovascular sensory system of
      the cat. Neuronal action potentials in the trigeminal nucleus were recorded while
      the superior sagittal sinus (SSS) or facial receptive field (RF) were stimulated
      electrically. Drugs, including the neuronal excitant glutamate, were applied to
      neurons via microiontophoresis. Results were obtained from 152 neurons activated
      with A-delta latencies by SSS stimulation and by glutamate. The NO donor S
      nitrosoglutathione (SNOG, 50 nA) was applied iontophoretically to 41 neurons
      during SSS stimulation and 13 neurons during pulsatile glutamate ejection.
      Responses to both modes of stimulation were enhanced by SNOG; the proportion of
      neurons enhanced was 56% to SSS stimulation and 59% to glutamate. The inhibitor
      of nitric oxide synthase (NOS), N(omega)-propyl-L-arginine (p-ARG, 50 nA) was
      applied iontophoretically to 17 neurons during stimulation of SSS and to 10
      neurons during pulsatile glutamate ejection. Responses to both stimuli were
      suppressed by p-ARG: The proportion of neurons suppressed were: to SSS
      stimulation 59% and to glutamate 80%. Microiontophoretic ejection of eletriptan
      (50 nA) reversibly suppressed responses of neurons to SSS stimulation, to RF
      electrical stimulation and to pulsatile iontophoretic application of glutamate.
      This suppression of responses was antagonised by the concurrent local
      iontophoretic application of the 5-HT1B/1D receptor antagonist GR127935 or by
      concurrent iontophoretic application of the selective 5-HT1D receptor antagonist
      BRL155732. These results suggest that glutamatergic mechanisms are important in
      sensory transmission in the trigeminovascular system and that they can be
      modulated by nitrergic and serotonergic mechanisms.

PMID- 15165836
TI  - Cannabinoid signaling in rat cerebellar granule cells: G-protein activation,
      inhibition of glutamate release and endogenous cannabinoids.
AB  - Previous studies have indicated that cannabinoids inhibit presynaptic
      neurotransmitter release in brain through CB1 receptors. To examine this issue in
      a primary neuronal culture system, rat cerebellar granule cells (CGCs) were
      prepared. [35S]GTPgammaS binding assays in saponin-permeabilized CGCs showed that
      G-protein activation by the CB1 agonist, WIN55212-2, and adenosine A1 agonist,
      phenylisopropyladenosine, was maximal during the second week in culture. Delta9
      tetrahydrocannabinol stimulated [35S]GTPgammaS binding to a lesser degree than
      WIN55212-2, and the antagonists SR141716A and AM281 acted as inverse agonists in
      intact CGCs, but not in CGC membrane preparations. Ten micromolar WIN55212-2 and
      Delta9-tetrahydrocannabinol decreased depolarization-evoked efflux of [3H]-D
      aspartate from CGCs by 32% and 13%, respectively. SR141716A and AM281 increased
      [3H]-D-aspartate release by 28%. The fatty acid amide hydrolase (FAAH) inhibitor
      phenylmethylsulfonyl fluoride (PMSF) and the anandamide uptake inhibitor AM404
      inhibited transmitter release, implying that the antagonist effects were mediated
      by blockade of endocannabinoid activity. Levels of endocannabinoids (both
      anandamide and 2-arachidonyl glycerol [2-AG]) in extracts of the cells and cell
      incubation buffer were increased by PMSF pre-treatment. Depolarization with KCl
      significantly decreased the amount of anandamide and 2-AG in PMSF-treated CGCs.
      These results suggest that endogenous cannabinoids inhibit neurotransmitter
      release in CGCs, which may also release endocannabioids upon neural stimulation.

PMID- 15165838
TI  - Enhanced antinociception by nicotinic receptor agonist epibatidine and adrenal
      medullary transplants in the spinal subarachnoid space.
AB  - Adrenal medullary transplants in the spinal subarachnoid space can reduce
      nociception, via the release of catecholamines and other analgesic substances,
      and this may be enhanced by stimulation of transplanted chromaffin cell surface
      nicotinic acetylcholine receptors (nAChRs). In addition, spinal nAChRs have been
      implicated in modulating nociception and can interact synergistically with alpha
      adrenergic agents. Thus, enhanced antinociception by potent nAChR agonists such
      as frog skin derivative epibatidine in adrenal-transplanted animals could
      potentially occur via multiple mechanisms, including nicotinic-alpha-adrenergic
      synergy and stimulation of chromaffin cell nicotinic receptors. In order to test
      this, male Sprague-Dawley rats were implanted with intrathecal catheters and
      either adrenal medullary or control striated muscle transplants in the spinal
      subarachnoid space at the lumbar enlargement. Animals were tested for nociceptive
      responses before and after intrathecal injection of several doses of epibatidine
      using acute analgesiometric tests (tail flick, paw pressure) and the formalin
      test. After adrenal medullary, but not control, transplantation, nociceptive
      thresholds to acute noxious stimuli were slightly but consistently elevated, and
      phase 2 formalin responses decreased. Following intrathecal injection of
      epibatidine, acute nociceptive response latencies were modestly elevated and
      phase 2 formalin flinches modestly suppressed in control animals, but only at the
      highest dose test, with some attendant motor side-effects. In contrast, in
      adrenal medullary-transplanted animals, epibatidine elevated responses to acute
      noxious stimuli and markedly suppressed phase 2 formalin responses in a dose
      related fashion. The enhanced antinociceptive effect following epibatidine was
      attenuated with either nAChR antagonist mecamylamine or alpha-adrenergic receptor
      antagonist phentolamine. The current results demonstrate that intrathecal
      injection of the nAChR ligand epibatidine can produce significant antinociception
      in adrenal-transplanted rats in both acute and tonic nociceptive tests and
      suggest that the use of nicotinic agents in combination with adrenal medullary
      transplantation could provide maximal therapeutic benefit by synergistically
      improving antinociception while avoiding the detrimental side-effects of these
      agents.

PMID- 15165839
TI  - Participation of brainstem nuclei in the pronociceptive effect of lesion or
      neural block of the anterior pretectal nucleus in a rat model of incisional pain.
AB  - The anterior pretectal nucleus (APtN) participates in nociceptive process and
      controls spinal nociceptive inputs, and its integrity reduces the severity of the
      responses to persistent injury. In this study we examined whether the
      pedunculopontine tegmental nucleus (PPTg) or the gigantocellularis nucleus pars
      alpha (GiA), stations that relay APtN inputs to the spinal cord, can control the
      persistent pain induced by a hind paw incision in rats with disrupted APtN. The
      withdrawal threshold to mechanical stimulation of the incised paw measured with
      von Frey filaments was significantly reduced in rats with contralateral APtN
      lesion or neural block of this nucleus with 2% lidocaine. Intrathecal xylamine,
      an inhibitor of noradrenaline uptake, inhibited the neural block of the APtN
      induced increase in the incisional pain. Injection of glutamate into the
      contralateral PPTg or ipsilateral GiA reduced the incisional pain. Neural block
      of the PPTg or GiA reduced the threshold, mainly in APtN-disrupted rats. We
      conclude that persistent noxious stimulation activates descending pathways
      involving the contralateral APtN and PPTg, and ipsilateral GiA. Disruption of the
      APtN allows the activation of alternative circuitry involving at least the PPTg
      and GiA as intermediary stations that might maintain the control of nociceptive
      inputs in the spinal cord, probably involving noradrenergic mechanisms.

PMID- 15165840
TI  - Blockade of neurotensin receptors affects differently hypo-locomotion and
      catalepsy induced by haloperidol in mice.
AB  - Antipsychotic drug treatment increases neurotensin (NT) neurotransmission, and
      the exogenous administration of NT produces antipsychotic-like effects in
      rodents. In order to investigate whether "endogenous" NT may act as a natural
      occurring antipsychotic or may mediate antipsychotic drug activity, the effects
      of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in
      different behavioural tests of locomotor activity using vehicle, amphetamine, or
      haloperidol in mice. SR 48692 (0.1-1 mg/kg, i.p.) and SR 142948A (0.03-0.1 mg/kg,
      i.p.) failed to affect mouse spontaneous locomotor activity and amphetamine
      induced (2.5 mg/kg, i.p.) hyper-locomotion. However, SR 48692 (0.1 and 0.3 mg/kg,
      i.p.) and SR 142948A (0.03 and 0.05 mg/kg, i.p.) significantly alleviated the
      reduction of locomotor activity elicited by haloperidol (0.01 and 0.04 mg/kg,
      s.c.) in vehicle- or amphetamine-treated mice. Finally, SR 48692 (0.3 mg/kg,
      i.p.) and SR 142948A (0.05 and 0.1 mg/kg, i.p.) increased mouse catalepsy
      produced by haloperidol (0.3 mg/kg, s.c.). The present results indicate that
      while endogenous NT is not involved in the modulation of either mouse spontaneous
      locomotor activity or amphetamine-induced hyper-locomotion, it might act by
      enhancing the therapeutic effects of haloperidol and by attenuating the
      extrapyramidal side effects elicited by this antipsychotic.

PMID- 15165841
TI  - Cell-specific role for epsilon- and betaI-protein kinase C isozymes in protecting
      cortical neurons and astrocytes from ischemia-like injury.
AB  - Activation of epsilon protein kinase C (epsilonPKC) has been shown to protect
      cardiac myocytes against ischemia and reperfusion injury. However, the role of
      PKC in ischemic brain injury is less well defined. Western blot analysis of
      murine neurons and astrocytes in primary culture demonstrated epsilon- and
      betaIPKC expression in both cell types. Activation of epsilonPKC increased in
      neuronal cultures in response to the ischemia-like insult of oxygen-glucose
      deprivation (OGD). Isozyme-specific peptide activators or inhibitors of PKC were
      applied at various times before, during and after the OGD period. Neuron
      astrocyte mixed cultures pretreated with a selective epsilonPKC activator peptide
      showed a significant reduction in neuronal injury after OGD and reperfusion,
      compared to cultures pretreated with control peptide. The epsilonPKC activator
      peptide counteracted the increased damage induced by pretreatment with the
      epsilonPKC-selective inhibitor peptide in relatively pure neuronal cultures
      subjected to OGD. Neither epsilonPKC activator nor inhibitor peptides affected
      injury of neurons when applied after OGD onset. In contrast, the betaIPKC
      selective inhibitor peptide increased injury in astrocyte cultures exposed to OGD
      at all application times tested. Our data demonstrate protection of neurons by
      selective activation of epsilonPKC but enhanced astrocyte cell death with
      selective inhibition of betaIPKC. Thus PKC isozymes exhibit cell type-specific
      effects on ischemia-like injury.

PMID- 15165843
TI  - Structural and functional characterization on the interaction of yeast TFIID
      subunit TAF1 with TATA-binding protein.
AB  - General transcription factor TFIID, consisting of TATA-binding protein (TBP) and
      TBP-associated factors (TAFs), plays a central role in both positive and negative
      regulation of transcription. The TAF N-terminal domain (TAND) of TAF1 has been
      shown to interact with TBP and to modulate the interaction of TBP with the TATA
      box, which is required for transcriptional initiation and activation of TATA
      promoter operated genes. We have previously demonstrated that the Drosophila TAND
      region of TAF1 (residues 11-77) undergoes an induced folding from a largely
      unstructured state to a globular structure that occupies the DNA-binding surface
      of TBP thereby inhibiting the DNA-binding activity of TBP. In Saccharomyces
      cerevisiae, the TAND region of TAF1 displays marked differences in the primary
      structure relative to Drosophila TAF1 (11% identity) yet possesses
      transcriptional activity both in vivo and in vitro. Here we present structural
      and functional studies of yeast TAND1 and TAND2 regions (residues 10-37, and 46
      71, respectively). Our NMR data show that, in yeast, TAND1 contains two alpha
      helices (residues 16-23, 30-36) and TAND2 forms a mini beta-sheet structure
      (residues 53-56, 61-64). These TAND1 and TAND2 structured regions interact with
      the concave and convex sides of the saddle-like structure of TBP, respectively.
      Present NMR, mutagenesis and genetic data together elucidate that the minimal
      region (TAND1 core) required for GAL4-dependent transcriptional activation
      corresponds to the first helix region of TAND1, while the functional core region
      of TAND2, involved in direct interaction with TBP convex alpha-helix 2, overlaps
      with the mini beta-sheet region.

PMID- 15165842
TI  - Sodium channel blocking activity of AM-36 and sipatrigine (BW619C89): in vitro
      and in vivo evidence.
AB  - Sodium channel blockers are neuroprotective against cerebral ischemia in animal
      models. A novel neuroprotective compound AM-36, when screened for activity at the
      most common receptor and ion channel binding sites, revealed activity at site 2
      Na+ channels. Studies then investigated this Na+ channel blocking activity in
      vitro and in vivo relative to other Na+ channel blockers, including the
      neuroprotective agent sipatrigine (BW619C89). AM-36 inhibited batrachotoxinin
      (BTX)-sensitive Na+ channel binding in rat brain homogenates with an IC50 of 0.28
      microM. Veratridine (100 microM)-induced neurotoxicity in murine cerebellar
      granule cells was completely inhibited by AM-36 (1.7 microM) compared to only
      partial inhibition by sipatrigine (26 microM). Veratridine-stimulated glutamate
      release, as measured through a microdialysis probe in the cortex of anesthetised
      rats, was inhibited by 90% by superfusion of AM-36 (1000 microM). In the
      endothelin-1 (ET-1) model of middle cerebral artery occlusion (MCAo) in conscious
      rats, both AM-36 (6 mg/kg i.p.) and sipatrigine (10 mg/kg i.p.) 30 min post-MCAo
      significantly reduced cortical, but not striatal infarct volume. As the
      refractiveness of the striatum is likely to be dependent on the route and time of
      drug administration, AM-36 (1 mg/kg i.v.) was administered 3 or 5 h after MCAo
      and significantly reduced both cortical and striatal infarct volumes. The present
      studies demonstrate Na+ channel blocking activity of AM-36 both in vitro and in
      vivo, together with significant neuroprotection when administration is delayed up
      to 5 h following experimental stroke.

PMID- 15165844
TI  - DNA binding and in vivo function of C.elegans PEB-1 require a conserved FLYWCH
      motif.
AB  - Caenorhabditis elegans PEB-1 is a novel protein containing a DNA-binding domain
      in its N terminus, which includes a Cys/His-rich FLYWCH motif also found in
      Drosophila Mod(mdg4) proteins, and a large C-terminal domain of unknown function.
      PEB-1 is expressed in most pharyngeal cell types, but its molecular function
      remains unclear. Here we describe comparative and functional analyses of PEB-1.
      Characterization of the PEB-1 sequence from C.briggsae indicates highest
      conservation in the DNA-binding domain (including the FLYWCH motif) and the C
      terminus, suggesting two functional domains. The PEB-1 FLYWCH motif is essential
      for DNA-binding and in vivo function; however, it does not bind detectable metal.
      Likewise, the PEB-1 C terminus is necessary for full activity in vivo, although
      the DNA-binding domain alone is sufficient for partial function. Both the FLYWCH
      motif and the C-terminal domain are required for efficient nuclear localization,
      suggesting PEB-1 must bind DNA and other components to remain in the nucleus.
      Analysis of binding sites revealed a YDTGCCRW PEB-1 consensus-binding site, and
      matches to this consensus are widespread in the C.elegans genome.

PMID- 15165845
TI  - Distinct origins of tRNA(m1G37) methyltransferase.
AB  - The enzyme tRNA(m1G37) methyltransferase catalyzes the transfer of a methyl group
      from S-adenosyl-l-methionine (AdoMet) to the N1 position of G37 in the anticodon
      loop of a subset of tRNA. The modified guanosine is 3' to the anticodon and is
      important for maintenance of reading frame during decoding of genetic
      information. While the methyltransferase is well conserved in bacteria and is
      easily identified (encoded by the trmD gene), the identity of the enzyme in
      eukarya and archaea is less clear. Here, we report that the enzyme encoded by
      Mj0883 of Methanocaldococcus jannaschii is the archaeal counterpart of the
      bacterial TrmD. However, despite catalyzing the same reaction and displaying
      similar enzymatic properties, MJ0883 and bacterial TrmD are completely unrelated
      in sequence. The catalytic domain of MJ0883, when aligned with the five known
      structural folds (I-V) that have been described to bind AdoMet, is of the class I
      fold, similar to the ancient Rossmann fold that binds nucleotides. In contrast,
      the catalytic domain of the bacterial TrmD has the unusual class IV fold of a
      trefoil knot structure. Thus, both the sequence and structural arrangements of
      tRNA(m1G37) methyltransferase have distinct evolutionary origins among primary
      kingdoms, revealing an unexpected but remarkable non-orthologous gene
      displacement to achieve an important tRNA modification.

PMID- 15165846
TI  - Distinguishing humans from great apes with AluYb8 repeats.
AB  - Humans and chimpanzees share some 99% of DNA and amino acid identity, yet they
      exhibit important biomedical, morphological, and cognitive differences, difficult
      to accommodate within the remaining 1% of sequence diversity. Other types of
      genetic variation must be responsible for the taxonomic differences. Here we
      trace the evolution of AluYb8 repeats from a single origin at the roots of higher
      primates to a large increase in their number in humans. We identify nine AluYb8
      DNA repeats in the chimpanzee genome compared to over 2200 repeats in the human,
      which represents a 250-fold increase in the rate of change in the human lineage
      and far outweighs the 99% sequence similarity between the two species. It is
      estimated that the average age of the human Yb8Alus is about 3.3 million years
      (My); almost 10% of them are identical in sequence, and hence are of recent
      origin. Genomic variations of this magnitude, distinguishing humans from great
      apes have not been realized. This explosive Alu expansion must have had a
      profound effect on the organization of our genome and the architecture of our
      chromosomes, inferentially altering profiles of gene expression and chromosome
      choreography in cell division. Additionally, we conclude that this major
      evolutionary process of Alu proliferation is driven by internal forces, written
      in the chemistry of DNA, rather than by external selection.

PMID- 15165847
TI  - Fluorescence stopped-flow studies of single turnover kinetics of E.coli RecBCD
      helicase-catalyzed DNA unwinding.
AB  - We have developed and optimized a stopped-flow fluorescence assay for use in
      studying DNA unwinding catalyzed by Escherichia coli RecBCD helicase. This assay
      monitors changes in fluorescence resonance energy transfer (FRET) between a pair
      of fluorescent probes (Cy3 donor and Cy5 acceptor) placed on opposite sides of a
      nick in duplex DNA. As such, this is an "all-or-none" DNA unwinding assay. Single
      turnover DNA unwinding experiments were performed using a series of eight
      fluorescent DNA substrates containing duplex DNA regions ranging from 24 bp to 60
      bp. The time-courses obtained by monitoring Cy3 fluorescence display a distinct
      lag phase that increases with increasing duplex DNA length, reflecting the
      transient formation of partially unwound DNA intermediates. These Cy3 FRET time
      courses are identical with those obtained using a chemical quenched-flow kinetic
      assay developed previously. The signal from the Cy5 fluorescence probe shows
      additional effects that appear to specifically monitor the RecD helicase subunit.
      The continuous nature of this fluorescence assay enabled us to acquire more
      precise time-courses for many more duplex DNA lengths in a significantly reduced
      amount of time, compared to quenched-flow methods. Global analysis of the Cy3 and
      Cy5 FRET time-courses, using an n-step sequential DNA unwinding model, indicates
      that RecBCD unwinds duplex DNA with an average unwinding rate constant of kU =
      200(+/-40) steps s(-1) (mkU = 680(+/-12)bp s(-1)) and an average kinetic step
      size, m = 3.4 (+/-0.6) bp step(-1) (5 mM ATP, 10 mM MgCl(2), 30 mM NaCl, pH 7.0,
      5% (v/v) glycerol, 25.0 degrees C), in excellent agreement with the kinetic
      parameters determined using quenched-flow techniques. Under these same
      conditions, the RecBC enzyme unwinds DNA with a very similar rate. These methods
      will facilitate detailed studies of the mechanisms of DNA unwinding and
      translocation of the RecBCD and RecBC helicases.

PMID- 15165848
TI  - Effects of temperature and ATP on the kinetic mechanism and kinetic step-size for
      E.coli RecBCD helicase-catalyzed DNA unwinding.
AB  - The kinetic mechanism by which Escherichia coli RecBCD helicase unwinds duplex
      DNA was studied using a fluorescence stopped-flow method. Single turnover DNA
      unwinding experiments were performed using a series of fluorescently labeled DNA
      substrates containing duplex DNA regions ranging from 24 bp to 60 bp. All or no
      DNA unwinding time courses were obtained by monitoring the changes in
      fluorescence resonance energy transfer between a Cy3 donor and Cy5 acceptor
      fluorescent pair placed on opposite sides of a nick in the duplex DNA. From these
      experiments one can determine the average rates of DNA unwinding as well as a
      kinetic step-size, defined as the average number of base-pairs unwound between
      two successive rate-limiting steps repeated during DNA unwinding. In order to
      probe how the kinetic step-size might relate to a mechanical step-size, we
      performed single turnover experiments as a function of [ATP] and temperature. The
      apparent unwinding rate constant, kUapp, decreases with decreasing [ATP],
      exhibiting a hyperbolic dependence on [ATP] (K1/2=176(+/-30) microM) and a
      maximum rate of kUapp=204(+/-4) steps s(-1) (mkUapp=709(+/-14) bp s(-1)) (10 mM
      MgCl2, 30 mM NaCl (pH 7.0), 5% (v/v) glycerol, 25.0 degrees C). kUapp also
      increases with increasing temperature (10-25 degrees C), with Ea=19(+/-1) kcal
      mol(-1). However, the average kinetic step-size, m=3.9(+/-0.5) bp step(-1),
      remains independent of [ATP] and temperature. This indicates that even though the
      values of the rate constants change, the same elementary kinetic step in the
      unwinding cycle remains rate-limiting over this range of conditions and this
      kinetic step remains coupled to ATP binding. The implications of the constancy of
      the measured kinetic step-size for the mechanism of RecBCD-catalyzed DNA
      unwinding are discussed.

PMID- 15165849
TI  - Mechanisms of camptothecin resistance by human topoisomerase I mutations.
AB  - Human topoisomerase I relaxes superhelical tension associated with DNA
      replication, transcription and recombination by reversibly nicking one strand of
      duplex DNA and forming a covalent 3'-phosphotyrosine linkage. This enzyme is the
      sole target of the camptothecin family of anticancer compounds, which acts by
      stabilizing the covalent protein-DNA complex and enhancing apoptosis through
      blocking the advancement of replication forks. Mutations that impart resistance
      to camptothecin have been identified in several regions of human topoisomerase I.
      We present the crystal structures of two camptothecin-resistant forms of human
      topoisomerase I (Phe361Ser at 2.6A resolution and Asn722Ser at 2.3A resolution)
      in ternary complexes with DNA and topotecan (Hycamtin), a camptothecin analogue
      currently in widespread clinical use. While the alteration of Asn722 to Ser leads
      to the elimination of a water-mediated contact between the enzyme and topotecan,
      we were surprised to find that a well-ordered water molecule replaces the
      hydrophobic phenylalanine side-chain in the Phe361Ser structure. We further
      consider camptothecin-resistant mutations at seven additional sites in human
      topoisomerase I and present structural evidence explaining their possible impact
      on drug binding. These results advance our understanding of the mechanism of cell
      poisoning by camptothecin and suggest specific modifications to the drug that may
      improve efficacy.

PMID- 15165850
TI  - The role of DNA structure and dynamics in the recognition of bovine
      papillomavirus E2 protein target sequences.
AB  - The papillomavirus E2 transcription and replication factors bind to the DNA
      consensus ACCGN(4)CGGT sequence (E2-BS), through both direct and indirect readout
      mechanisms. The two symmetric half-sites ACCG.CGGT are highly conserved in the
      genomes and are hydrogen bound with E2. Although E2 does not contact the N4
      spacer, the affinities are modulated by the base composition of this DNA part.
      Nevertheless, the origin of either the global recognition mechanism or the spacer
      effect remains unclear, particularly in the case of the bovine papillomavirus
      type 1 E2 (BPV-1-E2) system, used as model to study the papillomaviruses. We
      present, herein, studies carried out on oligomers differently recognized by the
      BPV-1-E2 protein and based on molecular dynamic simulations including counterions
      and water. The sequences contain the conserved half-sites but three different
      spacers (CCAT, ACGT and AAAC), resulting in very high, high and low affinity
      targets for BPV-1-E2. In order to estimate how much the free DNAs resemble the
      bound conformations, comparisons are made with two DNAs extracted from E2-BS-BPV
      1 crystallographic complexes, representative of high and moderate affinity
      structures. The analysis of 15 ns trajectories reveals that the ACCG/CGGT half
      sites, whatever the spacer, have the same behavior and adopt average stable base
      pair parameters very close to those of the bound conformations. In contrast, the
      three different free spacers strongly differ in their BI <--> BII backbone
      dynamics. The low affinity AAAC spacer exhibits stable BI backbone conformations,
      the high affinity ACGT spacer is characterized by a dramatic instability of the
      CpG phosphate groups, and the CpA and GpG backbones in the very high affinity
      CCAT.ATGG spacer are trapped in BII conformations. All resemble more of the
      moderate affinity complex DNA than the high affinity one. Nevertheless, the
      particular behavior of the CCAT and ACGT backbones allows the emergence of BII
      rich spacers, a configuration reproducing both local and global helical features
      of the bound DNA conformation of the high affinity complex and favoring the minor
      groove curvature required in the complex. In particular, the CCAT-containing site
      spends almost half of the time in this form that well mimics the bound one. Thus,
      we propose that the E2 protein could take advantage of the invariant favorable
      structures of the half-sites to form a pre-complex, but would require a specific
      spacer intrinsic malleability to lock the interaction. Finally, the backbone
      conformational states, by their ability to translate information coded in the
      sequence into structural properties, provide insight into the mechanisms that
      contribute to fine binding site selection and specific nucleic acid ligand
      recognition.

PMID- 15165851
TI  - Location of tyrosine 315, a target for phosphorylation by cAbl tyrosine kinase,
      at the edge of the subunit-subunit interface of the human Rad51 filament.
AB  - Rad51 is a key element of recombinational DNA repair and its activity is
      regulated by phosphorylation of the tyrosine residue at position 315 by cAbl
      kinase. This phosphorylation could be involved in the resistance of cancer cells
      to chemotherapy. We have investigated the role of this residue by comparing the
      three-dimensional structures of human Rad51 and its prokaryotic homologue,
      Escherichia coli RecA. The residue appeared to be on the edge of the subunit
      subunit interacting site. The fluorescence intensity of the tryptophan residue
      inserted at position 315 of human Rad51 in the place of tyrosine was decreased by
      adding 3 M urea, although the protein was not unfolded as there was no large
      change in the fluorescence peak position or circular dichroism signal. This
      change in fluorescence occurred at a lower urea concentration when the protein
      was diluted, which favours dissociation. These results indicate that the change
      is related to the dissociation of Rad51 polymer and that residue 315 is close to
      the subunit-subunit interacting site. ATP and ADP, which affect the filament
      structure, caused a blue shift in the fluorescence peak. These nucleotides
      probably altered the subunit-subunit contacts and may thus affect the filament
      structure. Phosphorylation of this residue could therefore affect the formation
      and structure of the Rad51 filament. Correct prediction of subunit-subunit
      interface of Rad51 by simple comparison of structures of Rad51 and RecA supports
      the idea that Rad51 forms the filament in a similar way as does RecA.

PMID- 15165852
TI  - The reaction mechanism of phospholipase D from Streptomyces sp. strain PMF.
      Snapshots along the reaction pathway reveal a pentacoordinate reaction
      intermediate and an unexpected final product.
AB  - Almost all enzyme-catalysed phosphohydrolytic or phosphoryl transfer reactions
      proceed through a five-coordinated phosphorus transition state. This is also true
      for the phospholipase D superfamily of enzymes, where the active site usually is
      made up of two identical sequence repeats of an HKD motif, positioned around an
      approximate 2-fold axis, where the histidine and lysine residues are essential
      for catalysis. An almost complete reaction pathway has been elucidated by a
      series of experiments where crystals of phospholipase D from Streptomyces sp.
      strain PMF (PLD(PMF)) were soaked for different times with (i) a soluble poor,
      short-chained phospholipid substrate and (ii) with a product. The various crystal
      structures were determined to a resolution of 1.35-1.75 A for the different time
      steps. Both substrate and product-structures were determined in order to identify
      the different reaction states and to examine if the reaction actually terminated
      on formation of phosphatidic acid (the true product of phospholipase D action) or
      could proceed even further. The results presented support the theory that the
      phospholipase D superfamily shares a common reaction mechanism, although
      different family members have very different substrate preferences and perform
      different catalytic reactions. Results also show that the reaction proceeds via a
      phosphohistidine intermediate and provide unambiguous identification of a
      catalytic water molecule, ideally positioned for apical attack on the phosphorus
      and consistent with an associative in-line phosphoryl transfer reaction. In one
      of the experiments an apparent five-coordinate phosphorus transition state is
      observed.

PMID- 15165853
TI  - Towards a resolution of the stoichiometry of the fibroblast growth factor (FGF)
      FGF receptor-heparin complex.
AB  - The 22 members of the fibroblast growth factor (FGF) family have been implicated
      in cell proliferation, differentiation, survival, and migration. They are
      required for both development and maintenance of vertebrates, demonstrating an
      exquisite pattern of affinities for both protein and proteoglycan receptors.
      Recent crystal structures have suggested two models for the complex between FGFs,
      FGF receptors (FGFRs) and the proteoglycan heparan sulphate that mediates
      signalling, and have provided insight into how FGFs show differing affinities for
      the range of FGFRs. However, the physiological relevance of the two different
      models has not been made clear. Here, we demonstrate that the two complexes can
      be prepared from the same protein components, confirming that neither complex is
      the product of misfolded protein samples. Analyses of the complexes with mass
      spectrometry and analytical ultracentrifugation show that the species observed
      are consistent with the crystal structures formed using the two preparation
      protocols. This analysis supports the contention that both of the crystal
      structures reflect the state of the molecules in solution. Mass spectrometry of
      the complexes suggests that the stoichiometry of the complexes is 2 FGF1:2
      FGFR2:1 heparin, regardless of the method used to prepare the complexes. These
      observations suggest that the two proposed complex architectures may both have
      relevance to the formation of an in vivo signalling complex, with a combination
      of the two interactions contributing to the formation of a larger focal complex.

PMID- 15165854
TI  - Molecular structure and interaction of recombinant human type XVI collagen.
AB  - Collagen XVI is a minor component of at least two different extracellular
      fibrillar networks of specialized regions of skin and cartilage. In skin,
      collagen XVI is integrated into particular fibrillin-rich microfibrils lacking an
      amorphous elastin core. In cartilage, collagen XVI is a component of small
      heterotypic D-banded fibrils, mainly occurring in the territorial matrix of
      chondrocytes. Here, we present the first direct evidence for the molecular
      structure and functional properties of these fibril-associated collagens with
      interrupted triple helices (FACIT). We have expressed recombinantly the full
      length alpha1 chain of human collagen XVI in HEK 293 EBNA cells in large
      quantities using an episomal expression system. Secreted full-length recombinant
      collagen XVI forms stable disulfide-bonded homotrimers and is rapidly
      proteolytically processed to distinct fragments at specific protease sequence
      motifs, one resembling an aggrecanase recognition site. Limited trypsin digestion
      assays and thermal transition curves imply sequential thermal denaturation of
      individual triple helical domains of this recombinant collagen, similar to
      authentic collagen XVI. Molecular images of collagen XVI reveal rod-like
      molecules which harbor multiple sharp kinks attributing a highly flexible
      structure presumably introduced by non-collagenous (NC) regions. Terminally
      located cloverleaf-shaped nodules correspond to the large NC NC11 domain of
      trimeric collagen XVI. The total length of individual trimeric recombinant
      collagen XVI molecules constitutes about 240 nm as calculated by atomic force and
      negative staining electron microscopy. Recombinant collagen XVI interacts with
      fibrillin-1 and with fibronectin indicating multiple molecular interactions in
      which this ubiquitously expressed and versatile FACIT-collagen can participate.
      In vitro generated collagen XVI provides an indispensable tool for future
      determination of its function during supramolecular assembly of matrix aggregates
      and its role in maintenance, organization and interaction of fibrillar
      structures.

PMID- 15165855
TI  - Multiple time scale backbone dynamics of homologous thermophilic and mesophilic
      ribonuclease HI enzymes.
AB  - Backbone conformational fluctuations on multiple time scales in a cysteine-free
      Thermus thermophilus ribonuclease HI mutant (ttRNH(*)) are quantified using (15)N
      nuclear magnetic spin relaxation. Laboratory-frame relaxation data acquired at
      310 K and at static magnetic field strengths of 11.7, 14.1 and 18.8 T are
      analysed using reduced spectral density mapping and model-free approaches.
      Chemical exchange line broadening is characterized using Hahn-echo transverse and
      multiple quantum relaxation data acquired over a temperature range of 290-320 K
      and at a static magnetic field strength of 14.1 T. Results for ttRNH(*) are
      compared to previously published data for a mesophilic homologue, Escherichia
      coli ribonuclease HI (ecRNH). Intramolecular conformational fluctuations on the
      picosecond-to-nanosecond time scale generally are similar for ttRNH(*) and ecRNH.
      beta-Strands 3 and 5 and the glycine-rich region are more rigid while the
      substrate-binding handle region and C-terminal tail are more flexible in ttRNH(*)
      than in ecRNH. Rigidity in the two beta-strands and the glycine-rich region,
      located along the periphery of the central beta-sheet, may be associated with the
      increased thermodynamic stability of the thermophilic enzyme. Chemical exchange
      line broadening, reflecting microsecond-to-millisecond time scale conformational
      changes, is more pronounced in ttRNH(*) than in ecRNH, particularly for residues
      in the handle and surrounding the catalytic site. The temperature dependence of
      chemical exchange show an increase of approximately 15 kJ/mol in the apparent
      activation energies for ttRNH(*) residues in the handle compared to ecRNH.
      Increased activation barriers, coupled with motion between alpha-helices B and C
      not present in ecRNH, may be associated with the reduced catalytic activity of
      the thermophilic enzyme at 310 K.

PMID- 15165856
TI  - Structural basis of human cytoglobin for ligand binding.
AB  - Cytoglobin (Cgb), a newly discovered member of the vertebrate globin family,
      binds O(2) reversibly via its heme, as is the case for other mammalian globins
      (hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb)). While Cgb is expressed
      in various tissues, its physiological role is not clearly understood. Here, the X
      ray crystal structure of wild type human Cgb in the ferric state at 2.4A
      resolution is reported. In the crystal structure, ferric Cgb is dimerized through
      two intermolecular disulfide bonds between Cys38(B2) and Cys83(E9), and the
      dimerization interface is similar to that of lamprey Hb and Ngb. The overall
      backbone structure of the Cgb monomer exhibits a traditional globin fold with a
      three-over-three alpha-helical sandwich, in which the arrangement of helices is
      basically the same among all globins studied to date. A detailed comparison
      reveals that the backbone structure of the CD corner to D helix region, the N
      terminus of the E-helix and the F-helix of Cgb resembles more closely those of
      pentacoordinated globins (Mb, lamprey Hb), rather than hexacoordinated globins
      (Ngb, rice Hb). However, the His81(E7) imidazole group coordinates directly to
      the heme iron as a sixth axial ligand to form a hexcoordinated heme, like Ngb and
      rice Hb. The position and orientation of the highly conserved residues in the
      heme pocket (Phe(CD1), Val(E11), distal His(E7) and proximal His(F8)) are similar
      to those of other globin proteins. Two alternative conformations of the
      Arg84(E10) guanidium group were observed, suggesting that it participates in
      ligand binding to Cgb, as is the case for Arg(E10) of Aplysia Mb and Lys(E10) of
      Ngb. The structural diversities and similarities among globin proteins are
      discussed with relevance to molecular evolutionary relationships.

PMID- 15165857
TI  - Crystal structure of T state aspartate carbamoyltransferase of the
      hyperthermophilic archaeon Sulfolobus acidocaldarius.
AB  - Aspartate carbamoyltransferase (ATCase) is a model enzyme for understanding
      allosteric effects. The dodecameric complex exists in two main states (T and R)
      that differ substantially in their quaternary structure and their affinity for
      various ligands. Many hypotheses have resulted from the structure of the
      Escherichia coli ATCase, but so far other crystal structures to test these have
      been lacking. Here, we present the tertiary and quaternary structure of the T
      state ATCase of the hyperthermophilic archaeon Sulfolobus acidocaldarius
      (SaATC(T)), determined by X-ray crystallography to 2.6A resolution. The
      quaternary structure differs from the E.coli ATCase, by having altered interfaces
      between the catalytic (C) and regulatory (R) subunits, and the presence of a
      novel C1-R2 type interface. Conformational differences in the 240 s loop region
      of the C chain and the C-terminal region of the R chain affect intersubunit and
      interdomain interfaces implicated previously in the allosteric behavior of E.coli
      ATCase. The allosteric-zinc binding domain interface is strengthened at the
      expense of a weakened R1-C4 type interface. The increased hydrophobicity of the
      C1-R1 type interface may stabilize the quaternary structure. Catalytic trimers of
      the S.acidocaldarius ATCase are unstable due to a drastic weakening of the C1-C2
      interface. The hyperthermophilic ATCase presents an interesting example of how an
      allosteric enzyme can adapt to higher temperatures. The structural rearrangement
      of this thermophilic ATCase may well promote its thermal stability at the expense
      of changes in the allosteric behavior.

PMID- 15165858
TI  - New carbohydrate specificity and HIV-1 fusion blocking activity of the
      cyanobacterial protein MVL: NMR, ITC and sedimentation equilibrium studies.
AB  - Carbohydrate-binding proteins that bind their carbohydrate ligands with high
      affinity are rare and therefore of interest because they expand our understanding
      of carbohydrate specificity and the structural requirements that lead to high
      affinity interactions. Here, we use NMR and isothermal titration calorimetry
      techniques to determine carbohydrate specificity and affinities for a novel
      cyanobacterial protein, MVL, and show that MVL binds oligomannosides such as
      Man(6)GlcNAc(2) with sub-micromolar affinities. The amino acid sequence of MVL
      contains two homologous repeats, each comprising 54 amino acid residues. Using
      multi-dimensional NMR techniques, we show that MVL contains two novel
      carbohydrate recognition domains composed of four non-contiguous regions
      comprising approximately 15 amino acid residues each, and that these residues
      make numerous intermolecular contacts with their carbohydrate ligands. NMR
      screening of a comprehensive panel of di-, tri-, and high-mannose
      oligosaccharides establish that high-affinity binding requires at least the
      presence of a discrete conformation presented by Manbeta(1-->4)GlcNAc in the
      context of larger oligomannosides. As shown by sedimentation equilibrium and gel
      filtration experiments, MVL is a monodisperse dimer in solution, and NMR data
      establish that the three-dimensional structure must be symmetric. MVL inhibits
      HIV-1 Envelope-mediated cell fusion with an IC(50) value of approximately 30 nM.

PMID- 15165859
TI  - Folding of the villin headpiece subdomain from random structures. Analysis of the
      charge distribution as a function of pH.
AB  - The structure of the 36 residue villin headpiece subdomain is investigated with
      the electrostatically driven Monte Carlo method. The ECEPP/3 (Empirical
      Conformational Energy Program for Peptides) force field, plus two different
      continuum solvation models, were used to describe the conformational energy of
      the chain with both blocked and unblocked N and C termini. A statistical analysis
      of an ensemble of ab initio generated conformations was carried out, based on a
      comparison with a set of ten native-like structures derived from published
      experimental data, by using rigid geometry and NMR-derived constraints obtained
      at pH 3.7. The ten native-like structures satisfy the NMR-derived constraints.
      The whole ensemble of conformations of the terminally unblocked villin headpiece
      sub-domain, generated by using ECEPP/3 with a continuum solvation model, were
      subsequently evaluated at pH 3.7 with a potential function that includes ECEPP/3
      combined with a fast multigrid boundary element method. At pH 3.7, the lowest
      energy conformation found during the conformational search satisfies
      approximately 70% of both the distance and the dihedral-angle constraints, and
      possesses the characteristic packing of three phenylalanine residues that
      constitute the main part of the hydrophobic core of the molecule. On the other
      hand, computations at pH 3.7 and pH 7.0 for the ten native-like structures
      satisfying the NMR-derived constraints indicate a substantial change in the
      charge distribution for each type of amino acid residue with the change in pH.
      The results of this study provide a basis to understand the effect of the
      interactions, such as hydrophobicity, charge-charge interaction and solvent
      polarization, on the stability of this small alpha-helical protein.

PMID- 15165860
TI  - Design and crystal structure of bacteriophage T4 mini-fibritin NCCF.
AB  - Fibritin is a fibrous protein that forms "whiskers" attached to the neck of
      bacteriophage T4. Whiskers interact with the long tail fibers regulating the
      assembly and infectivity of the virus. The fibritin trimer includes the N
      terminal domain responsible for attachment to the phage particle and for the
      collar formation, the central domain forming a 500 A long segmented coiled-coil
      structure, and the C-terminal "foldon" domain. We have designed a "mini" fibritin
      with most of the coiled-coil domain deleted, and solved its crystal structure.
      The non-helical N-terminal part represents a new protein fold that tightly
      interacts with the coiled-coil segment forming a single domain, as revealed by
      calorimetry. The analysis of the crystal structure and earlier electron
      microscopy data on the collar-whisker complex suggests the necessity of other
      proteins to participate in the collar formation. Crystal structure determination
      of the N-terminal domain of fibritin is the first step towards elucidating the
      detailed structure and assembly mechanism of the collar-whisker complex.

PMID- 15165861
TI  - Differential arrangements of conserved building blocks among homologs of the
      Rad50/Mre11 DNA repair protein complex.
AB  - Structural maintenance of chromosomes (SMC) proteins have diverse cellular
      functions including chromosome segregation, condensation and DNA repair. They are
      grouped based on a conserved set of distinct structural motifs. All SMC proteins
      are predicted to have a bipartite ATPase domain that is separated by a long
      region predicted to form a coiled coil. Recent structural data on a variety of
      SMC proteins shows them to be arranged as long intramolecular coiled coils with a
      globular ATPase at one end. SMC proteins function in pairs as heterodimers or as
      homodimers often in complexes with other proteins. We expect the arrangement of
      the SMC protein domains in complex assemblies to have important implications for
      their diverse functions. We used scanning force microscopy imaging to determine
      the architecture of human, Saccharomyces cerevisiae, and Pyrococcus furiosus
      Rad50/Mre11, Escherichia coli SbcCD, and S.cerevisiae SMC1/SMC3 cohesin SMC
      complexes. Two distinct architectural arrangements are described, based on the
      way their components were connected. The eukaryotic complexes were similar to
      each other and differed from their prokaryotic and archaeal homologs. These
      similarities and differences are discussed with respect to their diverse
      mechanistic roles in chromosome metabolism.

PMID- 15165862
TI  - Unification of the folding mechanisms of non-two-state and two-state proteins.
AB  - We have collected the kinetic folding data for non-two-state and two-state
      globular proteins reported in the literature, and investigated the relationships
      between the folding kinetics and the native three-dimensional structure of these
      proteins. The rate constants of formation of both the intermediate and the native
      state of non-two-state folders were found to be significantly correlated with
      protein chain length and native backbone topology, which is represented by the
      absolute contact order and sequence-distant native pairs. The folding rate of two
      state folders, which is known to be correlated with the native backbone topology,
      apparently does not correlate significantly with protein chain length. On the
      basis of a comparison of the folding rates of the non-two-state and two-state
      folders, it was found that they are similarly dependent on the parameters that
      reflect the native backbone topology. This suggests that the mechanisms behind
      non-two-state and two-state folding are essentially identical. The present
      results lead us to propose a unified mechanism of protein folding, in which
      folding occurs in a hierarchical manner, reflecting the hierarchy of the native
      three-dimensional structure, as embodied in the case of non-two-state folding
      with an accumulation of the intermediate. Apparently, two-state folding is merely
      a simplified version of hierarchical folding caused either by an alteration in
      the rate-limiting step of folding or by destabilization of the intermediate.

PMID- 15165863
TI  - Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8
      dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase
      class.
AB  - Dihydroneopterin aldolase (DHNA) catalyses a retroaldol reaction yielding 6
      hydroxymethyl-7,8-dihydropterin, a biosynthetic precursor of the vitamin,
      tetrahydrofolate. The enzyme is a potential target for antimicrobial and anti
      parasite chemotherapy. A gene specifying a dihydroneopterin aldolase from
      Arabidopsis thaliana was expressed in a recombinant Escherichia coli strain. The
      recombinant protein was purified to apparent homogeneity and crystallised using
      polyethylenglycol as the precipitating agent. The crystal structure was solved by
      X-ray diffraction analysis at 2.2A resolution. The enzyme forms a D(4)-symmetric
      homooctamer. Each polypeptide chain is folded into a single domain comprising an
      antiparallel four-stranded beta-sheet and two long alpha-helices. Four monomers
      are arranged in a tetrameric ring, and two of these rings form a hollow cylinder.
      Well defined purine derivatives are found at all eight topologically equivalent
      active sites. The subunit fold of the enzyme is related to substructures of
      dihydroneopterin triphosphate epimerase, GTP cyclohydrolase I, and
      pyruvoyltetrahydropterin synthase, which are all involved in the biosynthesis of
      pteridine type cofactors, and to urate oxidase, although some members of that
      superfamily have no detectable sequence similarity. Due to structural and
      mechanistical differences of DHNA in comparison with class I and class II
      aldolases, a new aldolase class is proposed.

PMID- 15165864
TI  - Electrostatics of ion stabilization in a ClC chloride channel homologue from
      Escherichia coli.
AB  - The structural determinants of electrostatics of ion stabilization within EcClC,
      a ClC-type chloride channel homologue from Escherichia coli, are studied using a
      continuum dielectric approximation. Specifically, the ion occupancy is
      investigated in the wild-type protein and a mutant thereof, and the contribution
      to the electrostatic binding free energy of local and non-local interactions is
      characterized at the single-residue level. This analysis shows that, in spite of
      the desolvation cost and the strong ion-ion repulsion, all previously reported
      binding sites can be occupied simultaneously. The stabilizing effect of the
      protein arises from hydrogen bonding as well as from longer-range favorable
      interactions, such as with the strictly conserved Lys131 side-chain. The latter
      is involved in the stabilization of the conserved GSGIP motif that delimits two
      of the binding sites. Interestingly, an additional low-affinity binding site,
      mediated by a structurally analogous motif including the side-chain of Arg340,
      can be identified on the extracellular side of the permeation pathway. Finally,
      it is shown that, in contrast to K-channels, and in analogy to the SBP/PBP
      sulfate/phosphate-binding proteins, the contribution of helix macrodipoles to
      chloride binding in EcClC is only marginal.

PMID- 15165866
TI  - Homotypic variation of canine flexor tendons: implications for the design of
      experimental studies in animal models.
AB  - Water, collagen and glycosamimoglycan contents, cross-sectional area, stiffness
      and elastic modulus were carefully quantitated in flexor digitorum superficialis
      tendons from mature canines. From these data the within- and between-animal
      variability was estimated and used to demonstrate sample size calculations for
      both two-group and paired (within-animal) study designs. The estimated between
      dog variance was typically 50% or less of the total variance for the parameters
      investigated. In other words, the correlation among the tendons within an animal
      for most measures was not strong. Therefore, for some variables (e.g., elastic
      modulus) in this animal and tendon model, there is no appreciable gain in
      statistical power by using a paired study design. A two-group design could be
      used, but any within-animal correlation must be accounted for in the analysis.
      For other variables such as collagen content, a paired design would gain
      substantial power.

PMID- 15165865
TI  - Identification of specific interactions that drive ligand-induced closure in five
      enzymes with classic domain movements.
AB  - In order to better understand ligand-induced closure in domain enzymes, open
      unliganded X-ray structures and closed liganded X-ray structures have been
      studied in five enzymes: adenylate kinase, aspartate aminotransferase, citrate
      synthase, liver alcohol dehydrogenase, and the catalytic subunit of cAMP
      dependent protein kinase. A sequential model of ligand binding and domain closure
      was used to test the hypothesis that the ligand actively drives closure from an
      open conformation. The analysis supports the assumption that each enzyme has a
      dedicated binding domain to which the ligand binds first and a closing domain. In
      every case, a small number of residues are identified to interact with the ligand
      to initiate and drive domain closure. In all cases except adenylate kinase, the
      backbone of residues located in an interdomain-bending region (hinge site) is
      identified to interact with the ligand to aid in driving closure. In adenylate
      kinase, the side-chain of a residue located directly adjacent to a bending region
      drives closure. It is thought that by binding near a hinge site the ligand is
      able to get within interaction range of residues when the enzyme is in the open
      conformation. Interdomain bending regions not involved in inducing closure are
      involved in control, helping to determine the location of the hinge axis.
      Similarities have been discovered between aspartate aminotransferase and citrate
      synthase that only come to light in the context of their dynamical behaviour in
      response to binding their substrate. Similarity also exists between liver alcohol
      dehydrogenase and cAMP-dependent protein kinase whereby groups on NAD and ATP,
      respectively, mimic the backbone of a single amino acid residue in a process
      where a three residue segment located at the terminus of a beta-sheet, moves to
      form hydrogen bonds with the mimic that resemble those found in a parallel beta
      sheet. This interaction helps to drive domain closure in a process that has
      analogy to protein folding.

PMID- 15165867
TI  - Investigation of biomechanical factors affecting rowing performance.
AB  - It was hypothesized that a crew's rowing performance was predictable based on
      their total propulsive power, synchrony (a real-time comparison of rower
      propulsive force magnitudes) and total drag contribution (a measure of the
      rowers' effect on shell drag forces during the recovery), quantities calculated
      from individual rower's force-time profiles and recovery kinematics. A rowing
      pair was equipped with transducers to gather shell velocity, propulsive blade
      force, oar angular position and seat displacement. Eight subjects (four port,
      four starboard) participated in two rounds of data collection. The first round
      pairings were random, while the second round pairings were assigned based on
      Round 1 results. Regression analysis and ANCOVA were used to test the validity of
      assumptions inherent in the predictive model and, if applicable, explore a linear
      model predicting rowing performance based on total propulsive power, synchrony
      and total drag contribution. Total propulsive power, synchrony and total drag
      contribution were correlated and further were affected by pairing, violating
      assumptions inherent in the linear model. The original hypothesis was not
      supported based on these violations. Important findings include (1) performance
      cannot be predicted using the simple linear model proposed, (2) rowers' force
      time profiles are repeatable between trials, with some but not all rowers
      adapting their force-time profile dependent on their pair partner, presumably in
      an effort to increase the level of synchrony between the two, and (3) subtle
      biomechanical factors may play a critical role in performance.

PMID- 15165868
TI  - Numerical simulation of the mechanics of a yeast cell under high hydrostatic
      pressure.
AB  - The mechanical effects of the compression of a yeast cell (Saccharomyces
      cerevisiae) under high hydrostatic pressure used for the processing of food and
      food ingredients are modelled and simulated with the finite-element method. The
      cell model consists of a cell wall, cytoplasm a lipid filled vacuole and the
      nucleus. Material parameters have been taken from literature or have been derived
      from thermodynamic relationships of water and lipids under high hydrostatic
      pressure. The model has been validated for a pressure load up to 250 MPa.
      Comparison of the volume reduction to in situ experimental observations reveals
      very good agreement. Dimensional analysis of the governing equations shows that
      transient pressure application in a high-pressure food process does not enhance
      structural inactivation (mechanical damage), unless pressure oscillation
      frequencies of 700 MHz are applied. The deformation of the cell under pressure
      deviates strongly from isotropic volume reduction. Especially, organelle
      membranes exhibit large effective strain values. Hydrostatic stress conditions
      are preserved in the interior part of the cell. A pressure load of 400 MPa, which
      is critical upon disruption of cell organelle membranes, generates an effective
      strain up to 80%. In the cell wall, the stress state is heterogeneous. Von-Mises
      stress reaches the critical value upon failure of the cell wall of 70+/-4 MPa at
      a pressure load between 415 and 460 MPa.

PMID- 15165870
TI  - Load transfer across the scapula during humeral abduction.
AB  - Stress analysis in the individual parts of the scapula under normal physiological
      conditions is necessary to understand the load transfer mechanism, its relation
      with morphology of bone and to analyse the deviations in stress patterns due to
      implantation of the glenoid. The purpose of this study was to obtain stress
      distribution in the scapula during abduction of the arm and to obtain a
      qualitative estimate of the function of coracoacromial ligament. An accurate
      three-dimensional (3D) finite element (FE) model of the natural scapula has been
      developed for this purpose, using computed tomography data and shell-solid
      modelling approach. The model was experimentally validated. A musculoskeletal
      shoulder model of forces that calculates all muscle, ligament and joint reaction
      forces, in six load cases (30-180 degrees) during unloaded humeral abduction was
      used as applied loading conditions for the 3D FE model. High tensile and
      compressive stresses (15-60 MPa) were generated in the thick bony ridges of the
      scapula, like the scapular spine, lateral border, glenoid and acromion. High
      compressive stresses (45-58 MPa) were evoked in the glenoid and at the connection
      of glenoid-scapular spine-infraspinous fossa. The stresses in the infraspinous
      fossa and supraspinous fossa were low (0.05-15 MPa). These results indicated that
      the transfer of major muscle and joint reaction take place predominantly through
      the thick bony ridges, whereas the fossa area act more as attachment sites of
      large muscles. During humeral abduction, coracoacromial ligament was stretched,
      and presumably will be under tension.

PMID- 15165869
TI  - A strain energy function for arteries accounting for wall composition and
      structure.
AB  - Identification of a Strain Energy Function (SEF) is used when describing the
      complex mechanical properties of soft biological tissues such as the arterial
      wall. Classic SEFs, such as the one proposed by Chuong and Fung (J. Biomech. Eng.
      105(3) (1983) 268), have been mostly phenomenological and neglect the
      particularities of the wall structure. A more structural model was proposed by
      Holzapfel et al. (J. Elasticity 61 (2000) 1-48.) when they included the
      characteristic angle at which the collagen fibers are helically wrapped,
      resulting in an excellent SEF for applications such as finite element modeling.
      We have expanded upon the idea of structural SEFs by including not only the wavy
      nature of the collagen but also the fraction of both elastin and collagen
      contained in the media, which can be determined by histology. The waviness of the
      collagen is assumed to be distributed log-logistically. In order to evaluate this
      novel SEF, we have used it to fit experimental data from inflation-extension
      tests performed on rat carotids. We have compared the results of the fit to the
      SEFs of Choung and Fung and Holzapfel et al. The novel SEF is found to behave
      similarly to that of Holzapfel et al., both succeed in describing the typical S
      shaped pressure-radius curves with comparable quality of fit. The parameters of
      the novel SEF obtained from the fitting, bearing the physical meaning of the
      elastic modulus of collagen, the elastic modulus of elastin, the collagen
      waviness, and the collagen fiber angle, were compared to experimental data and
      discussed.

PMID- 15165871
TI  - Gear ratios at the limb joints of jumping dogs.
AB  - An increase in gear ratio of the limb extensor muscles during joint extension has
      been suggested to be a mechanism that facilitates optimal power production by
      skeletal muscles. The objectives of this study were to: (1) measure gear ratios
      at the wrist, elbow, shoulder, ankle, knee, and hip joints of jumping dogs, (2)
      compute the work performed by each of these joints, and (3) measure muscle
      shortening velocity for a joint exhibiting an increasing gear ratio during joint
      extension. The gear ratio out-lever was computed by dividing the ground reaction
      force (GRF) moment by the GRF, whereas the in-lever was directly measured as the
      perpendicular distance from the joint center to the line of action of the
      extensor muscle. In addition, changes in fascicle length were measured from the
      vastus lateralis muscle using sonomicrometry. Of the joints examined, only the
      gear ratios at the shoulder and knee joints increased during jumping in a manner
      that could facilitate peak power production of actively shortening muscles. The
      vastus lateralis was found to shorten at an average velocity of 3.20 muscle
      lengths per second. This is similar to estimates of shortening velocity that
      produce peak muscular power in mammals the size of dogs. Additionally, the knee
      extensors were found to produce a large proportion (26.6%) of the positive
      external work of the limbs. These observations suggest that dynamic gearing in
      jumping dogs may allow the extensor muscles of the knee joint to shorten in a way
      that maximizes their power production.

PMID- 15165873
TI  - Myosin head mechanical performance under different conformational change
      mechanisms.
AB  - The present paper puts forward a mathematical approach to model the
      conformational changes of the myosin head due to ATP hydrolysis, which determine
      the head swinging and consequent sliding of the actin filament. Our aim is to
      provide a simple but effective model simulating myosin head performance to be
      integrated into the overall model of sarcomere mechanics under development at our
      Laboratory (J. Biomech. 34 (2001) 1607). We began by exploring myosin head
      mechanics in recent findings about myosin ultrastructure, morphology and
      energetics in order to calculate the working stroke distance (WS) and the force
      transmitted to the actin filament during muscle contraction. Two different
      working stroke mechanisms were investigated, assuming that the swinging of the
      myosin head occurs either as a consequence of purely conformational changes
      (Science 261 (1993a) 58) or by thermally driven motion (ratchet mechanism)
      followed by conformational changes (Cell 99 (1999) 421). Our results show that
      force and WS values vary markedly between the two models. The maximum force
      generated is about 10 pN for the first model and 31 pN for the second model, and
      the WSs are about 13 and 4 nm, respectively. These results are then discussed and
      compared with published data. The experimental data used for comparison are
      scarce and non-homogeneous; hence, the final remarks do not lead to definite
      conclusions. In any event, relatively speaking, the first model is more coherent
      with experimental findings.

PMID- 15165872
TI  - A new method to investigate in vivo knee behavior using a finite element model of
      the lower limb.
AB  - Several finite element models have been developed for estimating the mechanical
      response of joint internal structures, where direct or indirect in vivo
      measurement is difficult or impossible. The quality of the predictions made by
      those models is largely dependent on the quality of the experimental data (e.g.
      load/displacement) used to drive them. Also numerical problems have been
      described in the literature when using implicit finite element techniques to
      simulate problems that involve contacts and large displacements. In this study, a
      unique strategy was developed combining high accuracy in vivo three-dimensional
      kinematics and a lower limb finite element model based on explicit finite element
      techniques. The method presents an analytical technique applied to a dynamic
      loading condition (impact during hopping on one leg). The validation of the lower
      limb model focused on the response of the whole model and the knee joint in
      particular to the imposed 3D femoral in vivo kinematics and ground reaction
      forces. The approach outlined in this study introduces a generic tool for the
      study of in vivo knee joint behavior.

PMID- 15165874
TI  - Flow pattern and shear stress distribution of distal end-to-side anastomoses. A
      comparison of the instantaneous velocity fields obtained by particle image
      velocimetry.
AB  - OBJECTIVE: To describe the local hemodynamics and pressure losses of crural
      bypass anastomoses using instantaneous velocity fields acquired by particle image
      velocimetry (PIV). METHODS: Silastic models of a Taylor patch, a Miller cuff and
      a femoro-crural patch prosthesis (FCPP) were attached to a circuit driven by a
      Berlin Heart, providing a pulsatile flow with an amplitude of 450 to 25 ml/min
      (mean 200 ml/min). An outflow resistance of 0.5 mmHg/ml/min (peripheral
      resistance units, PRU) was modeled using small silastic tubes providing a phase
      shift of -12 degrees between flow and pressure curves. The working fluid
      consisted of a glycerine/water mixture with a viscosity of 4 mPas. Hollow glass
      spheres with a mean size of 9-13 microm were used as tracer particles.
      Instantaneous velocity fields were obtained by means of PIV and shear rates as
      well as shear stresses were calculated. Triggered by the flowmeter signal, 10
      measurements at 100 ms intervals per cardiac cycle were obtained. The pressures
      were measured on the inflow and at both distal outflows. The resulting mean
      pressure losses due to flow separation and distal fluid acceleration were
      calculated. RESULTS: Inside the Taylor patch anastomosis a large flow separation
      at the hood containing a clockwise rotating vortex was found. Additionally a
      smaller flow separation at the heel and a flow stagnation zone on the floor of
      the recipient artery were observed. Conversely, inside the Miller cuff a
      counterclockwise rotating vortex was seen inside a large heel flow separation.
      The FCPP also showed typical separation areas at the hood and heel of the
      anastomosis, although these were smaller compared to the other anastomoses.
      Inside the FCPP anastomosis no vortex creation was observed throughout the
      cardiac cycle. The mainstream velocities at the inlet levels were comparable for
      the three anastomoses. A significant fluid acceleration was present at the
      antegrade as well as the retrograde outlets of the Taylor and Miller cuff, while
      the fluid acceleration at the antegrade outflow of the FCPP was small, which was
      attributed to the end-to-end configuration of the antegrade FCPP leg. The
      calculated normalized antegrade and retrograde pressure losses for the Taylor
      form were 0.90 and 0.88, for the Miller cuff 0.89 and 0.86 and for the FCPP 0.94
      and 0.86, respectively. The shear stresses inside the flow separations of the
      three anastomoses were significantly lower than normal wall shear stresses. High
      shear stress levels were found inside the transition zones between flow
      separation and high velocity mainstream. CONCLUSIONS: The flow pattern inside
      cuffed or funnel shaped anastomoses consists of large flow separation zones,
      which are thought to be associated with intimal hyperplasia development. In
      addition, fluid accelerations at the distal outlets result in pressure losses,
      which may contribute to impaired crural perfusion.

PMID- 15165875
TI  - Knee joint reaction force during tibial diaphyseal lengthening: a study on a
      rabbit model.
AB  - The in vivo passive knee joint reaction force was measured in a rabbit model of
      tibial diaphyseal lengthening. This was based on the assumption that limb
      lengthening creates soft tissue tension that compresses the joint surface and
      generates the joint contact force. A measurement method was developed that
      involved the distraction of the joint and the determination of the distraction
      force that just separates the joint surfaces. Sixteen immature (mean+/-SD age=9+/
      0.6 weeks) New Zealand White rabbits underwent 30% (left) tibial diaphyseal
      lengthening at a rate of two 0.4mm incremental lengthenings per day. The knee
      joint reaction force was measured at the end of lengthening (8 rabbits, mean+/-SD
      age=14+/-0.6 weeks) and five weeks after lengthening (8 rabbits, mean+/-SD
      age=19+/-0.7 weeks). An instrumented bilateral distractor and an extensometer
      were fixed cross the knee joint. The joint distraction force and distraction
      displacement were measured when the joint was distracted in steps and after the
      section of the Achilles tendon. The joint reaction force on the lengthened side
      was significantly higher than the control side at both time points (mean+/-SD
      44.4+/-7.8 N v. 27.2+/-4.0 N at the end of lengthening, 44.3+/-S6.5 N v. 31.3+/
      3.0 N at 5 weeks after lengthening). The contribution of the gastrocnemius to the
      joint reaction force on the lengthened side was also significantly higher than
      the control side at both time points (mean+/-SD 9.0+/-1.3N v. 2.8+/-0.8 N at the
      end of lengthening, 5.3+/-1.4N v. 2.7+/-0.5N at 5 weeks after lengthening). There
      were significant knee and ankle joint contractures at the end of lengthening, as
      evidenced by decreased range of motion (mean+/-SD 27+/-8 degrees and 36+/-13
      degrees, respectively), which remained 5 weeks after lengthening (mean+/-SD 26+/
      6 degrees and 35+/-8 degrees, respectively). The gastrocnemius contributed about
      20% of the joint reaction force, indicating that changes in the other intra- and
      extra-articular structures due to joint contracture may be more important in
      generating the joint reaction force.

PMID- 15165876
TI  - Simulated influence of osteoporosis and disc degeneration on the load transfer in
      a lumbar functional spinal unit.
AB  - As life expectancy increases, age-related disorders and the search for related
      medical care will expand. Osteoporosis is the most frequent skeletal disease in
      this context with the highest fracture risk existing for vertebrae. The aging
      process is accompanied by systemic changes, with the earliest degeneration
      occurring in the intervertebral discs. The influence of various degrees of disc
      degeneration on the load transfer was examined using the finite element method.
      The effect of different possible alterations of the bone quality due to
      osteoporosis was simulated by adjusting the corresponding material properties and
      their distribution and several loadings were applied. An alteration of the load
      transfer, characterised by changed compression stiffness and strain distributions
      as well as magnitudes, due to osteoporotic bone and degenerated discs was found.
      When osteoporosis was simulated, the stiffness was substantially decreased,
      larger areas of the cancellous bone were subjected to higher strains and strain
      maxima were increased. Increasing ratios of transverse isotropy in the
      osteoporotic bone yielded smaller effects than reduced bone properties. Including
      a degenerated disc mainly altered the strain distribution. Combining osteoporosis
      and degenerated discs reduced the areas of cancellous bone subjected to
      substantial strain. Based on these results, it can be concluded that the
      definition of a healthy disc in osteoporotic spines might be considered as a
      worst-case scenario. One attempt to evaluate the progress of osteoporosis can be
      made by introducing increasing degrees of anisotropy. If several parameters in a
      model are changed to simulate degeneration, it should be pointed out how each
      individual definition influences the overall result.

PMID- 15165877
TI  - Is the trunk movement more perturbed after an asymmetric than after a symmetric
      perturbation during lifting?
AB  - Low back injury is associated with sudden movements and loading. Trunk motion
      after sudden loading depends on the stability of the spine prior to loading and
      on the trunk muscle activity in response to the loading. Both factors are not
      axis-symmetric. Therefore, it was hypothesized that the effects on trunk dynamics
      would be larger after an asymmetric than after a symmetric perturbation. Ten
      subjects lifted a crate in which, prior to lifting, a mass was displaced to the
      front or to the side without the subjects being aware of this. Crate and subject
      movements, crate reaction forces and muscle activity were recorded. From this,
      the stability prior to the perturbation was estimated, and the trunk angular
      kinematics and moments at the lumbo-sacral joint were calculated. Both
      perturbations only minimally affected the trunk kinematics, although the
      stability of the spine prior to the lifting movement was higher in the sagittal
      plane than in the frontal plane. In both conditions the stability appeared to be
      sufficient to absorb the applied perturbation.

PMID- 15165878
TI  - The deformation of an adherent leukocyte under steady shear flow: a numerical
      study.
AB  - Leukocyte adhesion is a pathophysiological process in which the balance between
      hemodynamic and adhesion forces (molecular bonds) plays a key role. In this work,
      we studied the deformation of an adherent leukocyte and calculated the forces
      exerted on it. Three model cells were proposed, considering the leukocyte as a
      single drop, a compound drop, and a nucleus drop, representing a cell without
      nucleus, a cell with a nucleus, and a nucleus only, respectively. These model
      cells were supposedly adherent to a smooth substrate under steady shear flow. Our
      numerical results showed that all three model cells deformed in function of the
      initial contact angle, capillary number, and Reynolds number. The single drop was
      the most deformable, while the nucleus drop was the most resistant to the
      external flow. Each of the model cells showed maximum cell deformation at a high
      Reynolds number. The distribution of pressure on the cell confirmed the existence
      of a high-pressure region downstream of the drop, which retarded further
      deformation of the cell and provided a positive lift force on the drop. The
      consideration of a highly viscous nucleus can correct the over evaluation of the
      cell deformation in a flow.

PMID- 15165879
TI  - A mathematical model to predict the in vivo pulsatile drag forces acting on
      bifurcated stent grafts used in endovascular treatment of abdominal aortic
      aneurysms (AAA).
AB  - Endovascular treatment of abdominal aortic aneurysms (AAA) is a promising new
      alternative to the traditional surgical repair. However, the endovascular
      approach suffers problems such as stent graft migration, endoleaks and stent
      mechanism breakage. Fatigue failure is believed to be the major cause of stent
      graft migration and device breakage. Knowledge of the in vivo forces acting on
      such devices is a basic requirement for the design of a successful endovascular
      device. Using a Fourier series trigonometric fit of a typical pressure and flow
      relationship, a mathematical model, using the control volume method, was
      developed to predict the pulsatile drag forces acting on various bifurcated stent
      graft geometries. It was found that for an iliac angle of 30 degrees, a proximal
      diameter of 24 mm and an iliac diameter of 12 mm, the drag force varied, over the
      cardiac cycle, between 3.9 and 5.5 N in the axial direction. It was noted that
      for a specific iliac angle the drag force variation with proximal diameter
      approximates a quadratic fit, with an increase in proximal diameter producing an
      increase in drag force. The more compliant the aorta the higher the drag force.
      Previously published results demonstrated the axial loads (axial drag forces)
      required for stent graft migration for certain stents types are lower than the
      drag forces calculated in this study. It is believed that the results of this
      study can provide guidelines for the quantitative analyses of the in vivo drag
      forces experienced by stent grafts and could therefore be used as design criteria
      for such devices.

PMID- 15165880
TI  - Age-related and regional differences in the stress-strain and stress-relaxation
      behaviours of the rat incisor periodontal ligament.
AB  - Groups of rats were killed at 2, 6, 12, and 24 months of age. From dissected left
      and right mandibles in each rat, three pairs of transverse sections were cut at
      the incisal, middle, and basal regions of the incisor. One section in each pair
      was loaded until failure and a stress-strain curve for the periodontal ligament
      (PDL) was obtained. The other section was loaded to up to 50% of the maximum
      shear stress as determined from the contralateral section and then kept at a
      constant strain for 10 min, to obtain the stress-relaxation curve at the same
      region of the PDL. The maximum shear stress and toughness increased with age at
      the incisal region and the maximum shear strain increased with age at the incisal
      and middle regions. The tangent modulus decreased with advancing age at the
      middle region. The stress-relaxation during 10 min decreased with advancing age
      at the incisal and basal regions, but not at the middle region. The relaxation
      process was well described by a sum of three exponential decay functions,
      reflecting the short-, medium-, and long-term relaxation components. The age
      related decrease in the relaxation was mainly attributable to increases in the
      ratio and relaxation time of the long-term relaxation component. These results
      suggest that with advancing age the mechanical strength and toughness of the PDL
      are enhanced mostly at the incisal region and that the viscous fraction is
      relatively decreased at the incisal and basal regions along the long axis of the
      rat incisor.

PMID- 15165881
TI  - Influence of ligament stiffness on the mechanical behavior of a functional spinal
      unit.
AB  - Data on the stiffnesses of spinal ligaments are required for analytical studies
      on the mechanical behavior of spinal segments. Values obtained experimentally
      vary widely in the literature. A finite element model of an L3/L4 functional
      spinal unit was used to determine the influence of ligament stiffness on
      intersegmental rotation and forces in the ligaments. The lowest values for
      ligament stiffness selected from the literature were used in one set of
      calculations, and the highest values were simulated in a second set. The
      nonlinear model was loaded with pure moments of 7.5 and 15 Nm in the three main
      anatomical planes. The mechanical behavior of the functional spinal unit was
      strongly influenced by ligament stiffness. In some cases, a ligament with low
      stiffness does not carry any load, while the same ligament with high stiffness
      has to carry a high load. This indicates that finite element models of spinal
      segments have to be validated and that a realistic quantitative prediction of
      ligament forces is extremely difficult.

PMID- 15165882
TI  - A new semi-automated measurement technique based on X-ray pictures for ankle
      morphometry.
AB  - Knowledge of human joint morphology is important in orthopaedic surgery and in
      prosthesis design. The literature on quantitative morphological analysis of the
      ankle joint is particularly scarce. A semi-automated radiographic measurement
      method was developed to collect morphological measures of the ankle joint. The
      method was based on standard lateral and antero-posterior X-ray pictures of the
      ankle joint. These were then scanned and analysed by means of specialized
      software designed for the purpose, which requires minimal operator contribution.
      Accuracy of the method was experimentally assessed by in vitro direct
      measurements. Intra- and inter-operator variability was also tested. Accuracy was
      assessed to be within 1mm for most measurements. Repeatability was not affected
      by operator skill and was within 2mm. The newly proposed method was applied
      successfully on 15 male adult subjects and relevant results are reported. The
      method allows ankle morphology to be analysed in a large number of subjects
      providing reliable data for anthropometric statistics.

PMID- 15165883
TI  - Modeling mechanical stresses as a factor in the etiology of benign vocal fold
      lesions.
AB  - Vocal fold tissue lesions such as nodules and polyps are thought to develop in
      response to mechanical stress that occurs during vocal fold collision. Two
      computational models of vocal fold collision during voice production are used to
      investigate this hypothesis. A one-dimensional lumped mass model, whose
      parameters are derived from vocal fold tissue dimensions and material properties,
      predicts stress perpendicular to the direction of impact (normal stress). A
      previously published three-dimensional finite element model that incorporates the
      same dimensions and properties predicts the entire stress tensor. The hypothesis
      is supported by predictions from the finite element model that three components
      of normal stress and one component of shear stress are increased during collision
      in the typical location of lesions (i.e. the center of the superior medial edge
      of the vocal fold in the middle of the vibrating and contact region). The lumped
      mass model predicts that mechanical stress is negatively correlated with mucosal
      thickness (increased by voice warm-up and hydration), is positively correlated
      with driving force (proportional to voice intensity), and is affected by voice
      production method. These relationships are consistent with clinical observations
      of vocal fold lesion risk factors and have implications for improving prevention
      and treatment of benign vocal fold lesions.

PMID- 15165885
TI  - Happy birthday: forty years of FEBS.
AB  - The 2004 Federation of European Biochemical Societies (FEBS) Congress in Warsaw
      marks the 40th Anniversary of FEBS. To celebrate this event, the Executive
      Committee decided to publish a memoir, which chronicles the foundation of FEBS
      and its early development as well as presents an overview of FEBS activities and
      contributions that support the ever growing disciplines of biochemistry,
      molecular cell biology and molecular biophysics throughout Europe [Forty Years of
      FEBS Horst Feldmann (Ed.), Blackwell Publishers, Oxford 2003, on behalf of FEBS].
      This paper summarizes some of the most important aspects of this compilation.

PMID- 15165886
TI  - Lifting a chromosome: dosage compensation in Drosophila melanogaster.
AB  - Twofold differences in gene expression levels can be vital for an organism. This
      is beautifully illustrated by the process of 'dosage compensation' in Drosophila,
      which doubles transcription from the single male X chromosome to equal the mRNA
      levels originating from the two X chromosomes in female cells. Failure of the
      process leads to male-specific lethality. A number of recent publications have
      furthered our understanding of the ribonucleoprotein complex, which mediates
      dosage compensation and how it targets the male X chromosome. Deciphering the
      principles of X chromosome recognition and the nature of the chromatin
      configuration, that allows fine-tuning of transcription, remain the most
      interesting challenges.

PMID- 15165887
TI  - Plant chromatin -- epigenetics linked to ATP-dependent remodeling and
      architectural proteins.
AB  - Studies in organisms belonging to different eukaryotic kingdoms have revealed
      that the structural state of chromatin is controlled by interactions of DNA,
      small RNAs and specific proteins, linked to a self-reinforcing complex network of
      biochemical activities involving histone and DNA modifications and ATP-dependent
      nucleosome remodeling. However, these findings must now be reinterpreted in light
      of the recent discovery of the highly dynamic character of interphase chromosomes
      exemplified by the constant flux of enzymatic and structural proteins through
      both eu- and heterochromatin and by short- and long-range chromosome movements in
      the nucleus. The available data on chromosome organization in Arabidopsis
      thaliana and links between proteins influencing chromatin structure and DNA and
      histone modifications documented in this model plant provide strong supportive
      evidence for the dynamic nature of chromosomes.

PMID- 15165888
TI  - Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation,
      facilitates peptide-bond formation, chirality discrimination and antibiotics
      synergism.
AB  - The linkage between internal ribosomal symmetry and transfer RNA (tRNA)
      positioning confirmed positional catalysis of amino-acid polymerization. Peptide
      bonds are formed concurrently with tRNA-3' end rotatory motion, in conjunction
      with the overall messenger RNA (mRNA)/tRNA translocation. Accurate substrate
      alignment, mandatory for the processivity of protein biosynthesis, is governed by
      remote interactions. Inherent flexibility of a conserved nucleotide, anchoring
      the rotatory motion, facilitates chirality discrimination and antibiotics
      synergism. Potential tRNA interactions explain the universality of the tRNA CCA
      end and P-site preference of initial tRNA. The interactions of protein L2 tail
      with the symmetry-related region periphery explain its conservation and its
      contributions to nascent chain elongation.

PMID- 15165890
TI  - Replicable and recombinogenic RNAs.
AB  - This paper summarizes results of the 40-year studies on replication and
      recombination of RNA molecules in the cell-free amplification system of
      bacteriophage Q. Special attention is paid to the molecular colony technique that
      has provided for the discovery of the nature of "spontaneous" RNA synthesis by Q
      replicase and of the ability of RNA molecules to spontaneously rearrange their
      sequences under physiological conditions. Also discussed is the impact of these
      data on the concept of RNA World and on the development of new in vitro cloning
      and diagnostic tools.

PMID- 15165889
TI  - Employment opportunities for non-coding RNAs.
AB  - Analysis of the genomes of several higher eukaryotic organisms, including mouse
      and human, has reached the striking conclusion that the mammalian transcriptome
      is constituted in large part of non-protein-coding transcripts. Conversely, the
      number of protein-coding genes was initially at least overestimated. A growing
      number of studies report the involvement of non-coding transcripts in a large
      variety of regulatory processes. This review examines the different types of non
      coding RNAs (ncRNAs) and discusses their putative mode of action with particular
      reference to large ncRNAs and their role in epigenetic regulation.

PMID- 15165891
TI  - Viroids: the minimal non-coding RNAs with autonomous replication.
AB  - Viroids are small (246-401 nucleotides), non-coding, circular RNAs able to
      replicate autonomously in certain plants. Viroids are classified into the
      families Pospiviroidae and Avsunviroidae, whose members replicate in the nucleus
      and chloroplast, respectively. Replication occurs by an RNA-based rolling-circle
      mechanism in three steps: (1). synthesis of longer-than-unit strands catalyzed by
      host DNA-dependent RNA polymerases forced to transcribe RNA templates, (2).
      processing to unit-length, which in family Avsunviroidae is mediated by
      hammerhead ribozymes, and (3). circularization either through an RNA ligase or
      autocatalytically. Disease induction might result from the accumulation of viroid
      specific small interfering RNAs that, via RNA silencing, could interfere with
      normal developmental pathways.

PMID- 15165892
TI  - Circadian clocks and natural antisense RNA.
AB  - Eukaryotes regulate gene expression in a number of different ways. On a daily and
      seasonal timescale, the orchestration of gene expression is to a large extent
      governed by circadian clocks. These endogenous timekeepers enable organisms to
      prepare for predictable environmental conditions from one day to the next and
      thus allow adaptation to a given temporal niche. In general, circadian clocks
      have been shown to employ the classical transcriptional and posttranscriptional
      control mechanisms to generate rhythmicity. However, the discovery of antisense
      clock gene transcripts suggests that mechanisms of gene regulation operating
      through antisense RNA may also be integral to the circadian clockwork. Following
      a brief history of the impact of genetic and molecular techniques in aiding our
      understanding of circadian clocks, this review concentrates on the few examples
      of antisense clock gene transcripts so far investigated and their effect on
      circadian timing.

PMID- 15165893
TI  - Regulating eukaryotic gene expression with aptamers.
AB  - Aptamers are RNA or DNA oligonucleotides identified within a randomly synthesized
      library, through an in vitro selection procedure. The selected candidates display
      a pre-determined property of interest with respect to a given target. Successful
      selection has been carried out against targets ranging from small (amino acids,
      antibiotics) to macro-molecules (proteins, nucleic acids). They generally show an
      affinity in the nanomolar range and a high specificity of target recognition.
      Interestingly, aptamers selected against purified targets in the test tube retain
      their properties within cells. RNA aptamers can be generated in situ from an
      appropriate DNA construct or delivered as nuclease-resistant oligonucleotide
      analogues. For example, aptamers recognizing RNA structure through loop-loop
      interactions modulate the trans-activation of in vitro transcription mediated by
      the TAR RNA element of human immunodeficiency virus type 1. Consequently, they
      constitute both exquisite tools for functional genomics analysis and promising
      prototypes of therapeutic agents. Natural aptameric motifs have been identified
      within mRNA sequences, which upon binding to a metabolite control the expression
      of the encoded gene, which is generally involved in the biosynthesis of this
      particular metabolite.

PMID- 15165894
TI  - Immunotherapy and immunoselection -- tumour escape as the final hurdle.
AB  - Tumours are immunogenic and are commonly infiltrated by anti-cancer effector
      cells. Why, then, are they not completely rejected by the host? Unfortunately,
      tumours are Darwinian paragons, winning the battle against the forces of natural
      immune selection. Some of the latter can even act as double-edged swords,
      actually being subverted to become pro-tumorigenic. Prevention or reversal of
      tumour escape from the immune response therefore offers the possibility of
      reconstituting effective anti-tumour immunity and remains the major challenge for
      21st century tumour immunology.

PMID- 15165895
TI  - Conformational change in substrate binding, catalysis and product release: an
      open and shut case?
AB  - The role of conformational change in substrate binding, catalysis and product
      release is reviewed for 11 enzymes, for which crystal structures are available
      for the apo, substrate- and product-bound states. The extent of global
      conformational changes is measured, and the movements of the functional regions
      involved in catalysis and ligand binding are compared to the rest of the
      structure. We find that most of these enzymes undergo relatively small amounts of
      conformational change and particularly small changes in catalytic residue
      geometry, usually less than 1 A. In some enzymes there is significant movement of
      the binding residues, usually on surface loops.

PMID- 15165896
TI  - Selectivity and promiscuity in the interaction network mediated by protein
      recognition modules.
AB  - A substantial fraction of protein interactions in the cell is mediated by
      families of protein modules binding to relatively short linear peptides. Many of
      these interactions have a high dissociation constant and are therefore suitable
      for supporting the formation of dynamic complexes that are assembled and
      disassembled during signal transduction. Extensive work in the past decade has
      shown that, although member domains within a family have some degree of intrinsic
      peptide recognition specificity, the derived interaction networks display
      substantial promiscuity. We review here recent advances in the methods for
      deriving the portion of the protein network mediated by these domain families and
      discuss how specific biological outputs could emerge in vivo despite the observed
      promiscuity in peptide recognition in vitro.

PMID- 15165897
TI  - Yeast activator proteins and stress response: an overview.
AB  - Yeast, and especially Saccharomyces cerevisiae, are continuously exposed to rapid
      and drastic changes in their external milieu. Therefore, cells must maintain
      their homeostasis, which is achieved through a highly coordinated gene expression
      involving a plethora of transcription factors, each of them performing specific
      functions. Here, we discuss recent advances in our understanding of the function
      of the yeast activator protein family of eight basic-leucine zipper trans
      activators that have been implicated in various forms of stress response.

PMID- 15165898
TI  - Of flies and men; p53, a tumour suppressor.
AB  - The completion of the Drosophila genome sequencing project [Science 287 (2000)
      2185] has reconfirmed the fruit fly as a model organism to study human disease.
      Comparison studies have shown that two thirds of genes implicated in human
      cancers have counterparts in the fly [Curr. Opin. Genet. Dev. 11 (2001) 274; J.
      Cell Biol. 150 (2000) F23], including the tumour suppressor, p53. The suitability
      of the fruit fly to study the function of the tumour suppressor p53 is further
      exemplified by the lack of p53 family members within the fly genome, i.e., no
      homologues to p63 and p73 have been identified. Hence, there is no redundancy
      between family members greatly facilitating the analysis of p53 function. In
      addition, studying p53 in Drosophila provides an opportunity to learn about the
      evolution of tumour suppressors. Here, we will discuss what is known about
      Drosophila p53 in relation to human p53.

PMID- 15165899
TI  - Miniaturized proteomics and peptidomics using capillary liquid separation and
      high resolution mass spectrometry.
AB  - Knowledge of the protein and peptide content in a tissue or a body fluid is vital
      in many areas of medical and biomedical sciences. Information from proteomic and
      peptidomic studies may reveal alterations in expression due to, e.g., a disease
      and facilitate the understanding of the pathophysiology and the identification of
      biological markers. In this minireview, we discuss miniaturized proteomic and
      peptidomic approaches that have been applied in our laboratory in order to
      investigate the protein and peptide contents of body fluids (such as plasma,
      cerebrospinal and amniotic fluid), as well as extracted tissues. The methods
      involve miniaturized liquid separation, i.e., capillary liquid chromatography and
      capillary electrophoresis, combined with high resolution mass spectrometry (MS),
      i.e., Fourier transform ion cyclotron resonance MS. These approaches provide the
      opportunity to analyze samples of small volumes with high throughput, high
      sensitivity, good dynamic range and minimal sample handling. Also, the
      experiments are relatively easy to automate.

PMID- 15165900
TI  - Calcium and mitochondria.
AB  - The literature suggests that the physiological functions for which mitochondria
      sequester Ca(2+) are (1). to stimulate and control the rate of oxidative
      phosphorylation, (2). to induce the mitochondrial permeability transition (MPT)
      and perhaps apoptotic cell death, and (3). to modify the shape of cytosolic
      Ca(2+) pulses or transients. There is strong evidence that intramitochondrial
      Ca(2+) controls both the rate of ATP production by oxidative phosphorylation and
      induction of the MPT. Since the results of these processes are so divergent, the
      signals inducing them must not be ambiguous. Furthermore, as pointed out by
      Balaban [J. Mol. Cell. Cardiol. 34 (2002 ) 11259-11271], for any repetitive
      physiological process dependent on intramitochondrial free Ca(2+) concentration
      ([Ca(2+)](m)), a kind of intramitochondrial homeostasis must exist so that Ca(2+)
      influx during the pulse is matched by Ca(2+) efflux during the period between
      pulses to avoid either Ca(2+) buildup or depletion. In addition, mitochondrial
      Ca(2+) transport modifies both spatial and temporal aspects of cytosolic Ca(2+)
      signaling. Here, we look at the amounts of Ca(2+) necessary to mediate the
      functions of mitochondrial Ca(2+) transport and at the mechanisms of transport
      themselves in order to set up a hypothesis about how the mechanisms carry out
      their roles. The emphasis here is on isolated mitochondria and on general
      mitochondrial properties in order to focus on how mitochondria alone may function
      to fulfill their physiological roles even though the interactions of mitochondria
      with other organelles, particularly with endoplasmic and sarcoplasmic reticulum
      [Sci. STKE re1 (2004) 1-9], may also influence this story.

PMID- 15165901
TI  - Structural elements involved in electron-coupled proton transfer in cytochrome c
      oxidase.
AB  - Haem-copper oxidases are the last components of the respiratory chains in aerobic
      organisms. These membrane-bound enzymes energetically couple the electron
      transfer (eT) reactions associated with reduction of dioxygen to water, to proton
      pumping across the membrane. Even though the mechanism of proton pumping at the
      molecular level still remains to be uncovered, recent progress has presented us
      with the structural features of the pumping machinery and detailed information
      about the eT and proton-transfer reactions associated with the pumping process.

PMID- 15165902
TI  - Participation of endoplasmic reticulum and mitochondrial calcium handling in
      apoptosis: more than just neighborhood?
AB  - Over the past few years, extensive progress has been made in elucidating the role
      of calcium in the signaling of apoptosis. This has led to the characterization of
      calcium's role in the induction of apoptosis and in the regulation of effector
      proteases. In this review, we attempt to summarize the current knowledge
      regarding a segment of these studies, the interaction between the endoplasmic
      reticulum (ER) and mitochondria. This interface has been shown to play a crucial
      role in transferring agonist induced Ca(2+) signals to mitochondria during
      physiological processes. Recent evidence, however, extended the role of this
      Ca(2+) transfer to apoptotic pathways, showing that modulation of mitochondrial
      Ca(2+) uptake from the ER side has a prominent role in modulating cellular fate.

PMID- 15165904
TI  - The role of protein phosphatase-1 in the modulation of synaptic and structural
      plasticity.
AB  - Synaptic plasticity is a phenomenon contributing to changes in the efficacy of
      neuronal transmission. These changes are widely believed to be a major cellular
      basis for learning and memory. Protein phosphorylation is a key biochemical
      process involved in synaptic plasticity that operates through a tight balance
      between the action of protein kinases and protein phosphatases (PPs). Although
      the majority of research in this field has concentrated primarily on protein
      kinases, the significant role of PPs is becoming increasingly apparent. This
      review examines one such phosphatase, PP1, and highlights recent advances in the
      understanding of its intervention in synaptic and structural plasticity and the
      mechanisms of learning and memory.

PMID- 15165903
TI  - ABCG2 -- a transporter for all seasons.
AB  - The human ABCG2 (ABCP/MXR/BCRP) protein is a recently recognized ABC half
      transporter, which forms homodimers in the plasma membrane and actively extrudes
      a wide variety of chemically unrelated compounds from the cells. This protein
      protects our cells and tissues against various xenobiotics, with a crucial role
      in the intestine, liver, placenta, and the blood-brain barrier. Moreover, ABCG2
      seems to have a key function in stem cell protection/regulation, and also in
      hypoxic defense mechanisms. Widely occurring single nucleotide polymorphisms in
      ABCG2 may affect absorption and distribution, altering the effectiveness and
      toxicity of drugs in large populations. At the clinics, overexpression of ABCG2
      in tumor cells confers cancer multidrug resistance to a variety of newly
      developed anticancer agents. On the other hand, specific substrate mutants of
      ABCG2 are advocated for use as selectable markers in stem-cell based gene
      therapy.

PMID- 15165905
TI  - Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology
      of the adult brain.
AB  - More than 20 matrix metalloproteinases (MMPs) and four of their endogenous tissue
      inhibitors (TIMPs) act together to control tightly temporally restricted, focal
      proteolysis of extracellular matrix. In the neurons of the adult brain several
      components of the TIMP/MMP system are expressed and are responsive to changes in
      neuronal activity. Furthermore, functional studies, especially involving blocking
      of MMP activities, along with the identification of MMP substrates in the brain
      strongly suggest that this enzymatic system plays an important physiological role
      in adult brain neurons, possibly being pivotal for neuronal plasticity.

PMID- 15165907
TI  - Alternatives to telomerase: keeping linear chromosomes via telomeric circles.
AB  - Recombination is often capable of lengthening telomeres in situations where
      telomerase is absent. This recombinational telomere maintenance is often
      accompanied by telomeric instability including the accumulation of
      extrachromosomal telomeric circles (t-circles). Recent results of in vivo and in
      vitro experiments have suggested that t-circles can lead to the production of
      extended stretches of telomeric DNA by serving as templates for rolling-circle
      synthesis. This implies that t-circles can provide an efficient means of telomere
      elongation. The existence of t-circles in both nuclear and mitochondrial
      compartments of distantly related species suggests that they may be important
      contributors to an evolutionary conserved telomerase-independent mechanism of
      maintenance of telomeric tandem arrays.

PMID- 15165908
TI  - On the origin of floral morphological novelties.
AB  - Floral morphological novelties, like homeotic changes of whorl 1 organs, can
      easily arise by modifying existing regulatory networks. Ectopic expression of B
      function MADS-box genes in whorl 1 leads to a replacement of sepals by petals, as
      is found in the Liliaceae. In cases where leaf-like sepals or even inflated
      calyces develop, which ultimately envelop the mature fruit as in Physalis,
      ectopic expression of a vegetative MADS-box gene seems to be responsible. Current
      knowledge concerning the origin of such morphological novelties is reviewed.

PMID- 15165906
TI  - Repetitive sequences that shape the human transcriptome.
AB  - Only a small portion of the total RNA transcribed in human cells becomes mature
      mRNA and constitutes the human transcriptome, which is context-dependent and
      varies with development, physiology and pathology. A small fraction of different
      repetitive sequences, which make up more than half of the human genome, is
      retained in mature transcripts and shapes their function. Among them are short
      interspersed elements (SINEs), of which Alu sequences are most frequent, and
      simple sequence repeats, which come in many varieties. In this review, we have
      focused on the structural and functional role of Alu elements and trinucleotide
      repeats in transcripts.

PMID- 15165909
TI  - Endoreduplication and activation of the anaphase-promoting complex during
      symbiotic cell development.
AB  - Postembryonic development of plant organs requires a constant interplay between
      the cell cycle and the developmental programs. Upon endo- and exogenous signals,
      plant cells can enter, exit or modify the cell cycle. Alteration of mitotic
      cycles to endoreduplication cycles, where the genome is duplicated without
      mitosis, is common in plants and may play a role in cell differentiation. The
      switch from the mitotic to endocycles is regulated by Ccs52A, a plant orthologue
      of the yeast and animal Cdhl proteins, acting as substrate-specific activator of
      the anaphase-promoting complex E3 ubiquitin ligase. Here, several aspects of
      endoreduplication are discussed with special attention on nitrogen-fixing nodule
      development where endoreduplication is an integral part of symbiotic cell
      differentiation.

PMID- 15165910
TI  - Comparability of quality-of-care indicators for emergency coronary angioplasty in
      patients with acute myocardial infarction regardless of on-site cardiac surgery
      (report from the National Registry of Myocardial Infarction).
AB  - Initial reports have suggested that primary percutaneous coronary intervention
      (PCI) can be performed safely in selected hospitals without on-site cardiac
      surgery; however, quality-of-care indicators for primary PCI in these
      institutions is unknown. Therefore, symptom onset-to-door intervals, door-to
      balloon times, compliance with American College of Cardiology/American Heart
      Association (ACC/AHA) management guidelines, and in-hospital mortality were
      evaluated in 108,132 patients in 3 hospital settings in the National Registry of
      Myocardial Infarction: (1) diagnostic laboratories only (n = 47), (2) elective
      PCI only (n = 50), and (3) elective PCI and cardiac surgery (n = 562). Mean
      symptom onset-to-door intervals (127 minutes, 95% confidence interval 118 to135;
      134 minutes, 95% confidence interval 125 to 142; and 140 minutes, 95% confidence
      intervals 138 to 141; p = 0.01) and door-to-balloon intervals (104 minutes, 95%
      confidence interval 101 to 108; 116 minutes, 95% confidence interval 112 to 119;
      and 119 minutes, 95% confidence interval 118 to 120; p <0.0001) were shorter in
      hospitals without cardiac surgery. Adherence to ACC/AHA guidelines for
      medications within the first 24 hours (aspirin, beta blockers, angiotensin
      converting enzyme inhibitors) was greater in hospitals without cardiac surgery.
      There were comparable in-hospital mortality rates (3.2%, 4.2%, and 4.8%,
      respectively; p = 0.07) for patients with similar Thrombolysis In Myocardial
      Infarction risk scores; however, 4.7% of patients treated with primary PCI in
      hospitals without cardiac surgery were transferred to another institution. Thus,
      hospitals performing primary PCI without on-site cardiac surgery that
      participated in this registry have quality-of-care indicators and adherence to
      ACC/AHA management guidelines that are comparable to hospitals with on-site
      cardiac surgery. The lack of on-site cardiac surgery does not appear to adversely
      affect quality-of-care indicators in primary PCI.

PMID- 15165911
TI  - Effects of stent length and lesion length on coronary restenosis.
AB  - The choice of drug-eluting versus bare metal stents is based on costs and
      expectations of restenosis and thrombosis risk. Approaches to stent placement
      vary from covering just the zone of maximal obstruction to stenting well beyond
      the lesion boundaries (normal-to-normal vessel). The independent effects of
      stented lesion length, nonstented lesion length, and excess stent length, on
      coronary restenosis have not been evaluated for bare metal or drug-eluting
      stents. We analyzed the angiographic follow-up cohort (1,181 patients) from 6
      recent bare metal stent trials of de novo lesions in native coronary arteries.
      Stent length exceeded lesion length in 87% of lesions (mean lesion length 12.4 +/
      6.3 mm, mean stent length 20.0 +/- 7.9 mm, mean difference 7.6 +/- 7.9 mm). At 6
      to 9-month follow-up, the mean percent diameter stenosis was 39.1 +/- 20.1%. In
      an adjusted multivariable model of percent diameter stenosis, each 10 mm of
      stented lesion length was associated with an absolute increase in percent
      diameter stenosis of 7.7% (p <0.0001), whereas each 10 mm of excess stent length
      independently increased percent diameter stenosis by 4.0% (p <0.0001) and
      increased target lesion revascularization at 9 months (odds ratio 1.12, 95%
      confidence interval 1.02 to 1.24). Significant nonstented lesion length was
      uncommon (12.5% of cases). In summary, stent length exceeded lesion length in
      most stented lesions, and the amount of excess stent length increased the risk of
      restenosis independent of the stented lesion length. This analysis supports a
      conservative approach of matching stent length to lesion length to reduce the
      risk of restenosis with bare metal stents.

PMID- 15165912
TI  - Relation of metformin treatment to clinical events in diabetic patients
      undergoing percutaneous intervention.
AB  - Diabetic patients undergoing coronary interventions have worse clinical and
      angiographic outcomes than do patients without diabetes. Metformin, an insulin
      sensitizer, may decrease the occurrence of these outcomes. Diabetic patients in
      the Prevention of Restenosis with Tranilast and its Outcomes Trial were
      identified through their medical records (n = 2,772). In this trial, 1,110
      diabetic patients received nonsensitizer therapy (insulin and/or sulfonylureas)
      and 887 received sensitizer therapy (metformin with or without additional
      therapy). Logistic regression was used to obtain odds ratios (ORs) (sensitizer vs
      nonsensitizer therapy) of any clinical event (death, myocardial infarction, or
      ischemia-driven target vessel revascularization) and adjusted for multiple risk
      factors. Multivariate analysis showed no effect of lesion characteristics on
      clinical outcomes. Compared with patients on nonsensitizer therapy, those on
      sensitizer therapy showed an adjusted OR of 0.72 (95% confidence interval [CI]
      0.57 to 0.91, p = 0.005) for any clinical event. The differences between the
      nonsensitizer therapy group and the sensitizer group were attributable mainly to
      decreased rates of death (OR 0.39, 95% CI 0.19 to 0.77, p = 0.007) and myocardial
      infarction (OR 0.31, 95% CI 0.15 to 0.66, p = 0.002). In our retrospective
      analysis, use of metformin in diabetics undergoing coronary interventions
      appeared to decrease adverse clinical events, especially death and myocardial
      infarction, compared with diabetic patients treated with nonsensitizer therapy.

PMID- 15165913
TI  - Comparison of early and late results of a Carbofilm-coated stent versus a pure
      high-grade stainless steel stent (the Carbostent-Trial).
AB  - The long-term success of coronary interventions with stents is largely determined
      by the development of restenosis. The aim of this study was to compare a
      Carbofilm-coated and a pure stainless steel stent with regard to early and late
      adverse events. In this prospective, randomized trial, the Carbofilm-coated
      Carbostent and Sirius stent (same stent design, newly developed delivery system)
      were compared with the stainless steel stents S660, S670, and S7 (newly developed
      delivery system, same principal stent design with a few changes). The primary end
      point was relative late luminal loss, and secondary end points were diameter
      stenosis at 6 months, rate of restenosis, and major adverse cardiac events
      (MACEs) (myocardial infarction, reintervention, and death). From March 2000 to
      June 2002 at 18 centers in Canada and Europe, 420 patients were randomized.
      Relative late luminal loss (Carbofilm 28.9 +/- 23.0% vs stainless steel 26.7 +/-
      20.2%, p = 0.95) as the primary end point, absolute late luminal loss (1.00 +/-
      0.72 vs 0.93 +/- 0.62 mm, p = 0.95), net gain (1.32 +/- 0.82 vs 1.40 +/- 0.74 mm,
      p = 0.75), and the degree of stenosis (40.7 +/- 22.9% vs 38.0 +/- 20.1%, p =
      0.92), as well as restenosis rates (23.5% vs 15.9%, p = 0.09) and MACEs (20.1% vs
      13.7%, p = 0.11) were not significantly different. Thus, the Carbofilm coating of
      stents does not lead to an improvement in angiographic results or a reduction of
      restenosis rate and MACEs. These results agree with other trials using inactive
      coatings on stents, which also could not demonstrate any advantage over pure
      stainless steel stents.

PMID- 15165914
TI  - Prediction of the no-reflow phenomenon with ultrasonic tissue characterization in
      patients with anterior wall acute myocardial infarction.
AB  - The no-reflow phenomenon after acute myocardial infarction seems to be related to
      ischemic injury before reperfusion. Analyzing cardiac cycle-dependent variation
      of integrated backscatter (IBS) is a unique method to assess myocardial
      viability. In this study, the ability of ultrasonic tissue characterization with
      IBS to predict the no-reflow phenomenon was investigated in 90 patients with
      first anterior wall infarction who underwent successful primary percutaneous
      coronary intervention. IBS images were recorded on admission (before
      reperfusion), and the magnitude of the cyclic variation of IBS within the infarct
      zone was expressed as phase-corrected magnitude (PCM) by giving positive and
      negative values when it showed synchronous and asynchronous contraction,
      respectively. Myocardial contrast echocardiography was performed soon after
      reperfusion, and 21 patients showed substantial no-reflow. They had smaller PCM
      before reperfusion than patients without no-reflow (-1.6 +/- 1.9 vs 0.7 +/- 2.7
      dB, respectively; p = 0.0002). Multivariate logistic regression analysis revealed
      that PCM before reperfusion and the number of Q waves were the independent
      predictors of no reflow. Using -1.0 dB as the cut-off point, PCM predicted no
      reflow with 66.7% sensitivity and 81.2% specificity. These results indicate that
      the analysis of myocardial IBS could predict the no-reflow phenomenon before
      reperfusion.

PMID- 15165915
TI  - Combined assessment of thrombolysis in myocardial infarction flow grade,
      myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and
      myocardial reperfusion.
AB  - The restoration of epicardial and myocardial flow remains the primary goal of
      reperfusion therapy in patients with ST-segment elevation myocardial infarction,
      but the optimal method to assess this goal has not been defined. Thrombolysis In
      Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST
      segment resolution (STRes) were combined to formulate a new measure of successful
      reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3
      recent phase II clinical trials of ST-segment elevation myocardial infarction.
      Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before
      any intervention) after the initiation of reperfusion therapy. The complete
      restoration of perfusion, or the "trifecta," defined as the presence of TFG 3,
      MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The
      achievement of this trifecta was associated with low rates of 30-day mortality
      (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01),
      and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results
      were stratified with respect to subsequent percutaneous coronary intervention
      (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a
      strong predictor of better clinical outcomes, particularly in those patients who
      underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60
      minutes after fibrinolytic therapy and before PCI occurred in only 18% of
      patients but was associated with very low rates of death and CHF at 30 days. This
      new end point is proposed to evaluate the success of reperfusion therapy in
      patients who undergo early angiography.

PMID- 15165917
TI  - Evidence of adverse ventricular interdependence in patients with atrial septal
      defects.
AB  - Right ventricular (RV) volume overload is associated with left ventricular (LV)
      distortion and dysfunction. The availability of transcatheter device closure of
      secundum atrial septal defect (ASD) provides an ideal model for investigating the
      immediate effects of elimination of RV volume overload and avoiding the
      confounding effects of surgery on LV function. Echocardiograms before and after
      device closure of ASD were analyzed for ejection fraction, percent changes in
      cross-sectional area and circumference, percent changes in free wall and septal
      endocardial lengths, and eccentricity. We enrolled 34 patients (median age 9
      years) who underwent device closure of ASD (pulmonary to systemic shunt 1.6 +/-
      0.4). Ejection fraction and LV end-diastolic volume, reflective of chamber
      preload, were significantly decreased in the presence of RV volume overload and
      normalized after defect closure with normalization of LV shape. Altered LV
      geometry secondary to RV volume overload was associated with regional variation
      in preload,such that diastolic circumference, a surrogate of myofiber preload,
      increased after closure of ASD secondary to a small increase in LV free wall arc
      length in conjunction with a much more significant increase in septal length.
      Thus, LV dysfunction associated with RV volume overload is secondary to altered
      chamber geometry and decreased myofiber preload. This physiology is immediately
      reversible and is independent of heart rate and afterload.

PMID- 15165916
TI  - Relation of interleukin-6, C-reactive protein, and the prothrombotic state to
      transesophageal echocardiographic findings in atrial fibrillation.
AB  - Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke
      due to thromboembolism from the fibrillating left atrium, including its
      appendage. We hypothesized that indexes of inflammation (as indicated by C
      reactive protein and interleukin-6) and indexes of the prothrombotic state in AF
      that represent platelet activation (soluble P-selectin levels), endothelial
      damage or dysfunction (von Willebrand factor), coagulation (tissue factor and
      fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related
      to the presence of thromboembolic predictors on transesophageal echocardiography
      in patients with long-term AF. To test this hypothesis, we recruited 37 patients
      with long-term AF who were receiving warfarin therapy with an international
      normalized ratio of > or =2.0 for > or =3 weeks before transesophageal
      echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC)
      visible in the left atrium or left atrial appendage, 10 had complex atheromatous
      plaque in the descending aorta, 11 had peak left atrial appendage velocities < or
      =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight
      patients had > or =1 transesophageal echocardiographic (TEE) risk factor for
      thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P
      selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF
      with dense SEC than among those without. No significant associations were found
      for other TEE risk factors. Hematocrit was the only variable significantly
      associated with the presence of > or =1 TEE risk factor among patients with AF (p
      = 0.007) and the only independent associate of dense SEC after multivariate
      analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase
      in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only
      independent associate of dense SEC and > or =1 TEE risk factor, significant
      associations between dense SEC and the 2 indexes, C-reactive protein and soluble
      P-selectin, may indicate that mechanisms other than stasis are present with dense
      SEC. These observations support an "inflammatory hypothesis" in the pathogenesis
      of SEC that may have implications for thrombogenesis in AF.

PMID- 15165918
TI  - Evaluation of vardenafil and sildenafil on cardiac repolarization.
AB  - This novel study evaluated the effects of vardenafil and sildenafil on QT and
      corrected QT (QTc) duration using a model that minimizes experimental error to
      obtain the most accurate assessment of observed QTc effects. A placebo-controlled
      and positive-controlled, period-balanced, double-blinded, 6-way crossover study
      evaluated therapeutic and supratherapeutic oral doses of vardenafil (10 and 80
      mg, respectively) and sildenafil (50 and 400 mg, respectively), therapeutic doses
      of moxifloxacin (400 mg), and a placebo in 58 healthy men (mean age 53 years),
      with dosing every 3 days. Six replicate, 12-lead, digital electrocardiograms
      (ECGs) were recorded at 3 time points before and 5 time points after dosing to
      cover the time course of maximum exposure to study drugs and their metabolites.
      An independent laboratory blindly analyzed approximately 17,000 ECGs. For the
      placebo, mean change in QTcF (Fridericia) duration 1 hour after dose (approximate
      Tmax of vardenafil and sildenafil) was 0 ms (+/-0.7 SD). QT/QTc variability was
      small across regimens, indicating statistically powerful results. Moxifloxacin
      demonstrated an expected 8-ms mean change and was the only drug to prolong
      absolute QT. Placebo-corrected mean changes in QTcF duration (90% confidence
      interval) at 1 hour after dose were 8 ms (range 6 to 9) for vardenafil 10 mg and
      6 ms (range 5 to 8) for sildenafil 50 mg. QTci (linear and nonlinear per patient)
      yielded similar trends: 4 ms (range 3 to 6) for vardenafil 10 mg and 4 ms (range
      2 to 5) for sildenafil 50 mg. Dose response demonstrated very shallow QTc
      relations for study drugs. Therapeutic and supratherapeutic doses produced only
      small increases in the QTcF interval, which were considered to be clinically
      irrelevant. This well-controlled, statistically powerful study in middle-aged men
      demonstrated that vardenafil and sildenafil produced no increase of absolute QT
      and only similar, small increases of the QTc interval, with a shallow dose
      response curve. The study design and conduct may serve as a guide for future QT
      assessment of new drugs.

PMID- 15165919
TI  - Black tea increases coronary flow velocity reserve in healthy male subjects.
AB  - Epidemiologic studies suggest that tea consumption decreases the risk for
      cardiovascular events. However, there has been no clinical report examining the
      effects of tea consumption on coronary circulation. The purpose of this study was
      to evaluate the effects of black tea on coronary flow velocity reserve (CFVR)
      using transthoracic Doppler echocardiography (TTDE). This was a double-blind
      crossover study of 10 healthy male volunteers conducted to compare the effects of
      black tea and caffeine on coronary circulation. The coronary flow velocity of the
      left anterior descending coronary artery was measured at baseline and at
      hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The
      CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR
      before beverage consumption. All data were divided into 2 groups according to
      beverage type: group T (black tea) and group C (caffeine). Two-way analysis of
      variance showed a significant group effect and interaction in CFVR before and
      after beverage consumption (p = 0.001). CFVR significantly increased after tea
      consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of
      group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p =
      0.002). Acute black tea consumption improves coronary vessel function, as
      determined by CFVR.

PMID- 15165920
TI  - Effects of long-term prednisone (> or =5 mg) use on outcomes and complications of
      percutaneous coronary intervention.
AB  - To assess the potential risk of long-term steroid use in the setting of coronary
      angioplasty, 114 patients of 12,883 consecutively treated patients who were on
      long-term steroids were compared with those not taking steroids. Steroid use was
      not associated with increased risk of composite major ischemia events but was
      associated with a threefold risk (p = 0.01) of major vascular complications and a
      three- to fourfold risk (p = 0.026) of coronary perforation.

PMID- 15165921
TI  - Effect of pravastatin on myocardial perfusion after percutaneous transluminal
      coronary angioplasty.
AB  - We studied the effect of pravastatin on coronary perfusion after percutaneous
      transluminal coronary angioplasty. An exercise test performed within 2 weeks
      after percutaneous transluminal coronary angioplasty induced reversible perfusion
      defects in 66% of patients taking pravastatin and 64% of those taking placebo. At
      follow-up, the exercise test still induced reversible perfusion defects in 3% of
      patients taking pravastatin and 29% of those taking placebo.

PMID- 15165922
TI  - Impact of major side branch on periprocedural enzyme elevation and long-term
      outcome in patients undergoing percutaneous coronary intervention and
      brachytherapy for in-stent restenosis.
AB  - Side branch occlusion is 1 mechanism for the increase of creatine phosphokinase
      MB after percutaneous coronary intervention and is associated with long-term
      adverse events. We studied 248 patients who underwent brachytherapy for in-stent
      restenosis with and without side branches, compared levels of creatine
      phosphokinase-MB with procedural, in-hospital, and long-term clinical outcomes,
      and found that patients with side branches have increased levels of creatine
      phosphokinase-MB after percutaneous coronary intervention and higher rates of
      restenosis, target vessel, and target lesion revascularization at 6-month follow
      up.

PMID- 15165923
TI  - Creatine kinase-myocardial band isoenzyme elevation after percutaneous coronary
      interventions using sirolimus-eluting stents.
AB  - We evaluated predictors of increased periprocedural creatine kinase-MB isoenzyme
      levels after implantation of sirolimus-eluting stents with an intent to fully
      cover the diseased segment. The total stent length per patient (predisposing
      factor) and elective use of glycoprotein IIb/IIIa (protective factor) were
      independent predictors of increased creatine kinase-MB isoenzyme levels.

PMID- 15165924
TI  - Reperfusion assessment using myocardial contrast echocardiography in patients
      with ST-segment elevation acute myocardial infarction.
AB  - In this study, 29 patients underwent myocardial contrast echocardiography after
      presentation with ST-segment elevation acute myocardial infarction but before
      coronary angiography using a continuous infusion of microbubbles and real-time
      imaging with a low mechanical index. Patients with transmural perfusion defects
      at presentation subsequently had much larger infarctions (as measured by peak
      creatine phosphokinase-MB fraction) than did those with normal perfusion,
      indicating that myocardial contrast echocardiography may be a useful means to
      determine adequacy of reperfusion after thrombolytic therapy and in the selection
      of patients for adjunctive treatment, such as "rescue angioplasty."

PMID- 15165925
TI  - Lack of relation between imaging and physiology in ostial coronary artery
      narrowings.
AB  - This study compared ostial lesion angiographic severity with physiologic
      assessment and showed that, for diameter narrowings >70%, fractional flow
      reserves were >0.75 in 20 of 25 lesions and >0.75 in 30 of 30 lesions with <70%
      diameter narrowings. Using fractional flow reserve in all ostial narrowings > or
      =70% may prevent patients from undergoing unnecessary interventions.

PMID- 15165927
TI  - Predictors of rapid QRS widening in patients with coronary artery disease and
      left ventricular dysfunction.
AB  - To assess the predictors of rapid QRS widening in patients with chronic ischemic
      left ventricular dysfunction, 82 patients who underwent > or =2
      electrocardiograms and exercise Doppler echocardiography were studied. In a
      multivariate analysis, left ventricular end-diastolic volume, a large increase in
      mitral regurgitant volume during exercise, and diabetes emerged as independent
      predictors of QRS widening.

PMID- 15165926
TI  - Evaluation of isoproterenol in patients undergoing resuscitation for out-of
      hospital asystolic cardiac arrest (the Israel Resuscitation with Isoproterenol
      Study Prospective Randomized Clinical Trial).
AB  - The Israel Resuscitation with Isoproterenol Study included 79 consecutive
      patients with witnessed out-of-hospital asystolic cardiac arrest who were
      resuscitated with epinephrine and atropine and randomized to receive additional
      isoproterenol or no isoproterenol. The rate of return of spontaneous circulation
      and survival to hospital admission did not differ in patients receiving standard
      therapy and those receiving additional isoproterenol.

PMID- 15165929
TI  - Adverse events with concomitant use of simvastatin or atorvastatin and
      thiazolidinediones.
AB  - On the basis of adverse events reported to the US Food and Drug Administration,
      it was observed that atorvastatin-associated adverse event reports were 3.1 times
      more likely to list rosiglitazone or pioglitazone as a concomitant medication
      compared with simvastatin-associated adverse event reports.

PMID- 15165928
TI  - Relevance of homocysteine on brachial flow-mediated vasodilatation and carotid
      and femoral intima-media thickness in patients with hypercholesterolemia.
AB  - The relevance of homocysteine to brachial flow-mediated vasodilatation and
      carotid and femoral intima-media thickness was investigated in 192 patients with
      hypercholesterolemia. Low-density lipoprotein cholesterol and homocysteine levels
      predicted brachial flow-mediated vasodilatation, internal carotid mean intima
      media thickness, and intima-media thickening at all femoral sites. Homocysteine
      levels seem to be an additional factor in the initial atherosclerotic damage of
      patients with hypercholesterolemia.

PMID- 15165930
TI  - Effect of fluvastatin therapy on coronary flow reserve in patients with
      hypercholesterolemia.
AB  - Coronary flow reserve was evaluated using transthoracic Doppler echocardiography
      before and after 3 months of fluvastatin therapy in patients with
      hypercholesterolemia. Coronary flow reserve increased significantly after lipid
      lowering therapy, and coronary microcirculation was improved in patients with
      hypercholesterolemia.

PMID- 15165931
TI  - Comparison of outcomes of patients with symptomatic peripheral artery disease
      with and without atrial fibrillation (the West Birmingham Atrial Fibrillation
      Project).
AB  - In a multiethnic cohort of 388 patients admitted with symptomatic peripheral
      artery disease, atrial fibrillation was associated with emergency admission and
      increased mortality. Despite a greater prevalence of hypertension and diabetes in
      Afro-Caribbeans and diabetes in Indo-Asians, no significant differences were
      found in atrial fibrillation prevalence or mortality among different ethnic
      groups. Patients with symptomatic peripheral artery disease and atrial
      fibrillation should be regarded as "high risk" and managed with optimal medical
      therapy, including appropriate thromboprophylaxis and close follow-up.

PMID- 15165932
TI  - Presence and extent of angiographic coronary narrowing in patients with left
      bundle branch block.
AB  - Patients with coronary artery disease (CAD) and concomitant left bundle branch
      block have increased mortality compared with those with CAD but without left
      bundle branch block. We retrospectively analyzed the extent of CAD in 200
      patients with left bundle branch block referred for coronary angiography. Only
      13% had left main or 3-vessel CAD. These findings were irrespective of left
      ventricular (LV) function. Of the 65 patients with normal LV function, only 5
      (8%) had left main or 3-vessel disease, and of the 135 patients with depressed LV
      function, only 21 (16%) had left main or 3-vessel disease.

PMID- 15165933
TI  - Incidence, management, and outcome in significant pulmonary vein stenosis
      complicating ablation for atrial fibrillation.
AB  - This study summarizes our results in diagnosing and treating pulmonary vein
      stenosis complicating ablation for atrial fibrillation in 6 of 92 patients.
      Patients with significant pulmonary vein narrowing underwent either dilatation or
      dilatation plus stenting. Pulmonary vein intervention produced a favorable
      clinical course over the following 7 +/- 2 months despite significant restenosis
      in 2 patients.

PMID- 15165934
TI  - Comparison of effects of losartan, irbesartan, and candesartan on flow-mediated
      brachial artery dilation and on inflammatory and thrombolytic markers in patients
      with systemic hypertension.
AB  - We administered placebo, losartan 100 mg/day, irbesartan 300 mg/day, and
      candesartan 16 mg/day during 2 months to 122 patients with mild to moderate
      hypertension. Compared with placebo, angiotensin II type-1 receptor blockers
      significantly improved the percent flow-mediated dilator response to hyperemia (p
      = 0.019 by analysis of variance [ANOVA]) and reduced plasma levels of
      malondialdehyde (p = 0.005 by ANOVA). However, only irbesartan and candesartan
      therapies significantly lowered plasma levels of plasminogen activator inhibitor
      type-1 antigen (p <0.001 by ANOVA) with no differences between the 2, and only
      candesartan therapy significantly lowered plasma levels of monocyte
      chemoattractant protein-1 (p = 0.004 by ANOVA).

PMID- 15165935
TI  - Usefulness of an elevated troponin-I in predicting clinical events in patients
      admitted with acute heart failure and acute coronary syndrome (from the RITZ-4
      trial).
AB  - The relation of cardiac troponin-I (cTnI) to clinical outcomes was examined in
      patients with decompensated heart failure and concomitant acute coronary syndrome
      enrolled into the Randomized Intravenous TeZosentan 4 (RITZ-4) study. RITZ-4 was
      a multicenter, randomized, double-blind, placebo-controlled trial of the
      endothelin receptor antagonist tezosentan in patients admitted with acute heart
      failure and concomitant acute coronary syndrome. One hundred ninety-two patients
      were enrolled in this study. Patients with baseline cTnI values were included in
      this analysis, and the relation between cTnI and the composite clinical primary
      end point of RITZ-4 was evaluated.

PMID- 15165936
TI  - Effect of perindopril on platelet nitric oxide resistance in patients with
      chronic heart failure secondary to ischemic left ventricular dysfunction.
AB  - In 15 patients with chronic heart failure of ischemic origin who were not
      previously treated with angiotensin-converting enzyme inhibitors, platelets
      exhibited hyperaggregability and impaired responsiveness to the antiaggregatory
      and cyclic guanosine monophosphate-stimulatory effects of nitric oxide donor
      sodium nitroprusside compared with normal subjects; this was paralleled by
      increased blood levels of superoxide radicals. Treatment with perindopril for 4
      days significantly improved platelet responses to sodium nitroprusside; there was
      also a trend toward a decrease in superoxide radical levels.

PMID- 15165937
TI  - Outcome of subsequent pregnancy in patients with documented peripartum
      cardiomyopathy.
AB  - Subsequent pregnancy in 6 patients with previous peripartum cardiomyopathy
      resulted in reduction of ejection fraction by >10% in 5 patients at 1 month
      postpartum. Two patients with impaired ejection fraction at onset of subsequent
      pregnancy died 3 months postpartum due to heart failure despite optimal medical
      therapy. Deterioration of left ventricular function occurred uniformly postpartum
      and was accompanied by elevation of tumor necrosis factor-alpha plasma levels
      from 2.4 +/- 1.1 pg/ml at onset of subsequent pregnancy to 6.2 +/- 2.4 pg/ml at 1
      month postpartum.

PMID- 15165938
TI  - Safety of stress testing in patients with hypertrophic cardiomyopathy.
AB  - Two hundred sixty-three consecutive patients with hypertrophic cardiomyopathy
      underwent stress testing. Major complications occurred in 0.04% of patients and
      minor events occurred in 23%.

PMID- 15165939
TI  - Blood pressure dynamics during simulated ventricular tachycardia in patients
      after right ventricular outflow tract reconstruction mainly for tetralogy of
      Fallot compared with patients after ventricular septal defect closure.
AB  - We studied hemodynamic changes during simulated ventricular tachycardia using
      ventricular pacing. Hemodynamic deterioration during pacing is more significant
      in patients after right ventricular outflow tract reconstruction, especially in
      adults, than after closure of a ventricular septal defect. The cardiac autonomic
      nervous system has a significant impact on hemodynamics during simulated
      ventricular tachycardia.

PMID- 15165940
TI  - Relation of right ventricular pacing in tetralogy of Fallot to electrical
      resynchronization.
AB  - Prolonged QRS duration is a marker of increased sudden death risk in tetralogy of
      Fallot. Right ventricular pacing increased QRS duration in this population and
      could be counteracted with optimization of the atrioventricular interval in a
      subset of patients, potentially offering right ventricular resynchronization in
      patients with baseline right bundle branch block. Effective pacing therapy may
      require site-specific placement of pacing leads and precise pacemaker
      programming.

PMID- 15165941
TI  - Effect of multielement intravascular ultrasound on the anticoagulant potency of
      enoxaparin.
AB  - Two patients, treated with enoxaparin and eptifibatide, developed significant
      guide catheter-associated thrombus while undergoing intravascular ultrasound
      (IVUS). Using an ex vivo assay, we found that activation of a multielement IVUS
      catheter resulted in a decrease in anti-Xa activity and a decrease in clot
      formation time. This effect occurred rapidly and repeatedly after activation of
      the IVUS catheter.

PMID- 15165942
TI  - [What kind of prescriptions do you write for cardiac patients?].

PMID- 15165943
TI  - [Doppler index of myocardial performance and its relationship with mitral E wave
      deceleration time in acute Q-wave myocardial infarction].
AB  - OBJECTIVE: The objectives of the study were to assess myocardial systolic and
      diastolic functions by myocardial performance index (MPI) and its relationship
      with E - wave deceleration time (DT) in early phase of acute Q-wave myocardial
      infarction (MI). METHODS: We performed nongeometric Doppler-derived
      echocardiography to assess combined systolic and diastolic functions using
      myocardial performance index in 50 patients with acute Q-wave MI at early phase
      of events, (25 pts with anterior MI and 25 pts with inferior MI). The index is
      defined as the sum of the isovolumic contraction and isovolumic relaxation times
      divided by ventricular ejection time and was obtained by Doppler measurement from
      the diastolic mitral inflow and left ventricular outflow velocity-time intervals.
      RESULTS: As a result, the index was 0.54+/-0.1 in all patients with MI. We also
      estimated the higher MPI and DT values in anterior than in inferior MI (MPI:
      0.61+/-0.07 vs. 0.46+/-0.06, p<0.001; DT: 244+/-64 msec vs. 204+/-31.2 msec,
      p=0.005, respectively). Myocardial performance index was positively correlated
      with DT in inferior MI (r=0.42, p<0.035) and negatively correlated with anterior
      MI; (r=- 0.72, p=0.0001). CONCLUSION: These data suggest that Doppler-derived MPI
      reflects severity of global left ventricular dysfunction in early phase of acute
      MI and may be a useful parameter in these patients.

PMID- 15165945
TI  - [Physiological fundamentals of myocardial protection].

PMID- 15165944
TI  - [The effect of glutamate and aspartate on myocardial protection at
      cardiopulmonary bypass].
AB  - OBJECTIVE: To determine whether glutamat and aspartat enriched cold crystalloid
      cardioplegia which was given in antegrade way has any effect on the myocardial
      protection during cardiopulmonary bypass. METHODS: Thirty-four patients who were
      electively undergone open heart surgery at Osmangazi University Faculty of
      Medicine, thoracic and cardiovascular surgery department, between March 2001 and
      May 2001 were included in this study. The patients were divided in two groups,
      each consisting of 17 patients. In group 1 coronary artery bypass surgery (CABG)
      was performed in 11 patients, mitral valve replacement (MVR) in 3 patients,
      aortic valve replacement (AVR) in 1 patient and AVR and MVR in 2 patients. While
      in group 2 CABG was performed in 13 patients and MVR was done in 4 patients.
      Group 1 patients received antegrade glutamat and aspartat (15 mmol/L) enriched
      cold crystalloid cardioplegia and group 2 patients were given cold crystalloid
      cardioplegia by antegrade route. Age, gender, diabetes mellitus, hypertension,
      preoperative myocardial infarction, smoking, ejection fraction, aortic cross
      clamp time, need to defibrillation, inotropic support, and intraaortic balloon
      pump were recorded. The levels of cardiac troponin I (cTI) and creatine kinase
      myocardial band fraction (CK-MB) were measured in arterial blood samples at five
      different times. Statistical analysis was performed using Student's t-test and
      Chi-square test. RESULTS: There were no statistically significant differences in
      cTI and CK-MB values in blood samples taken at 5 different times pre and
      postoperatively between group 1 and group 2. CONCLUSION: It is concluded that
      glutamat and aspartat enriched cold crystalloid cardioplegia does not have any
      effect on myocardial protection.

PMID- 15165946
TI  - [Assessment of atrial pathologies in children using transesophageal
      echocardiography].
AB  - OBJECTIVE: Transesophageal echocardiography (TEE) is indicated for suspected
      atrial septal pathology and for monitoring of interventional procedures such as
      an atrial septal defect (ASD) closure during cardiac catheterization.
      Transesophageal echocardiography also helps to demonstrate postoperative
      complications and residual defects of complex congenital cardiac anomalies.
      METHODS: Transesophageal echocardiography was performed in 112 pediatric patients
      with or suspected atrial pathology at our institution between 1999-2002, using
      the standard techniques. The mean age was 8.7+/-4.2 years. RESULTS: In 45 of 112
      children the suspected atrial defects were confirmed with the TEE. Patent foramen
      ovale was correctly predicted in 13.4% of patients by TEE, but only in 8.7% of
      patients by echocardiography. Multiple ASD's were correctly defined in 4.1%, and
      high venosus defects were documented in 6.1% of children by the TEE. We used TEE
      in 13% of patients for detecting atrial vegetations in patients with possible
      endocarditis, and evaluation of the postoperative care of atrial surgery such as
      Fontan or Senning operations and total correction of abnormal pulmonary venous
      return. Successful transcatheter closure of 7 ASD's was accomplished under TEE
      guidance. CONCLUSION: Transesophageal echocardiography allows a much more
      detailed evaluation of atrial morphology than transthoracic echocardiography even
      in infants. Transesophageal echocardiography is also indicated during
      interventional procedures and postoperative evaluation of the atrial pathology.

PMID- 15165947
TI  - [Comparison of the antioxidant enzyme levels with the degree of dysfunction in
      patients with myocardial dysfunction].
AB  - OBJECTIVE: Myocardial dysfunction in patients with cardiomyopathy is proposed to
      occur due to membrane changes caused by oxidative stress. In our study we
      evaluate whether there is any relation between the degree of myocardial
      dysfunction and antioxidant enzymes. METHODS: We studied superoxide dismutase
      (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) enzyme activities from
      blood samples of 60 patients (30 patients had ejection fraction (EF) < %35 and 30
      patients had EF= %35-50) who have myocardial dysfunction according to clinical
      findings and two-dimensional echocardiography, and 20 healthy volunteers.
      RESULTS: We found erythrocyte SOD enzyme activities of patients with EF < %35
      (group 3) were significantly lower than in control subjects (group 1) (p=0.01).
      However in group 2 patients (EF= %35-50), erythrocyte SOD activities were found
      to be lower than in control subjects but this difference was not significant.
      Erythrocyte CAT and GSHPx enzyme activities of group 3 were also significantly
      lower than in control group (p=0.04 and p=0.02 respectively). CONCLUSION: In
      conclusion, reactive oxygen species play a significant role in the initiation and
      the progression of congestive heart failure. Increased free radicals levels may
      cause myocardial muscle dysfunction.

PMID- 15165948
TI  - [Comparison of electrocardiographic abnormalities in patients with ischemic and
      hemorrhagic stroke].
AB  - OBJECTIVE: The aim of this study was to compare the electrocardiographic (ECG)
      abnormalities in patients with acute ischemic and hemorrhagic stroke who had no
      history of heart disease. METHODS: During 12 months, 222 consecutive stroke
      patients were enrolled in this study. Of them 162 had ischemic stroke and 60 had
      hemorrhagic stroke. Frequency of arrhythmias and ECG changes were compared
      between two stroke groups. Electrocardiographic abnormalities included ischemia
      like changes (ST-segment depression or elevation, abnormal T and U waves), QTc
      prolongation and arrhythmias. RESULTS: Ischemic stroke patients were elder than
      hemorrhagic ones (64+/-14 years vs. 57+/-13 years, p=0.003). Other clinical
      characteristics were comparable in both groups. Ischemia-like ECG changes were
      found in 65% of ischemic stroke patients while they were observed in 57% of
      hemorrhagic stroke patients (p=0.33). Atrial fibrillation was more frequent in
      ischemic stroke than in hemorrhagic stroke (34% vs. 13%, p=0.01) patients.
      Individually, other ECG abnormalities were not different in both groups. With
      relation of ECG abnormalities to location of the brain lesion, there was a trend
      in favor of involvement of the temporal, frontal and parietal lobes. CONCLUSION:
      Regardless stroke-related lesion, ECG abnormalities can be seen frequently in
      stroke patients without primary heart disease. They can lead to diagnostic and
      therapeutic difficulties for cardiologists and neurologists.

PMID- 15165949
TI  - [Electrocardiographic changes in patients with cerebrovascular accidents].

PMID- 15165950
TI  - Internal mammary artery atherosclerosis in segments removed during coronary
      artery bypass grafting surgery and C.pneumoniae infection.
AB  - OBJECTIVE: Recent studies suggest the association of atherosclerotic
      cardiovascular disease with Chlamydia pneumoniae infection. We investigated C.
      pneumoniae DNA in internal mammarian artery (IMA) (used as a coronary bypass
      conduit) and its relationship with atherosclerosis. METHODS: Sixty-six
      consecutive patients who underwent coronary artery bypass grafting (CABG) during
      an eight-month period were included in this study. From all patients, we
      attempted to obtain surplus segments of harvested IMA grafts. The vessels were
      examined histopathologically, and presence of C. pneumoniae DNA in IMA grafts was
      assessed by polymerase chain reaction (PCR). RESULTS: C. pneumoniae DNA was found
      in 7 (10.6%) of 66 IMA specimens. The light microscopic examinations of IMA
      segments from the C. pneumonia positive group showed atherosclerotic intimal
      changes in four of the seven patients. These atherosclerotic changes were type II
      in three patients and type III in one patient according to the AHA
      classification. The rest of the IMA segments from 62 patients did not show any
      discernible atherosclerotic lesion. CONCLUSION: The IMA graft examination by PCR
      and histopathology may be helpful in the determination of future graft patency
      for IMA bypass surgery.

PMID- 15165951
TI  - Does radial artery harvesting cause any changes in the forehand circulation
      during the postoperative period? An angiographic study.
AB  - OBJECTIVE: The aim of this study was to evaluate angiographic changes in the
      ulnar and interosseous arteries, and the collateral circulation of forehand after
      harvesting radial artery. METHODS: Forty patients were studied between June 1998
      and June 2001. Study group consisted of 30 patients who received radial artery as
      a conduit for coronary artery bypass operation, and control group consisted of 10
      patients who did not undergo any cardiac or vascular operation before.
      Preoperative risk factors were similar between the two groups. All patients
      underwent angiographic evaluation to detect coronary artery and left forehand
      arterial circulation. RESULTS: Angiographic evaluation was performed 25.5 +/- 2.0
      months after the initial operation in the study group. Mean diameter of ulnar
      artery was 2.9 +/- 0.59 mm (range 2.1 - 4.8) in the study group and 3.2 +/- 0.8
      mm (range 1.5 t- 4.7) in the control group (p >0.05). Mean diameter of
      interosseous artery was significantly higher in the study group than in control
      one: 2.06 +/- 0.57 mm (range 1.2 t- 4.2) versus 1.46 +/- 0.79 mm (range 0.8 t-
      3.6); (p = 0.003). CONCLUSION: Although angiography was performed in a limited
      number of patients, interosseous artery rather than ulnar artery enlarged to
      compensate blood supply of forehand 25 months after harvesting the radial artery
      for coronary artery bypass grafting.

PMID- 15165953
TI  - The value and throughput of rest Thallium-201/stress Technetium -99m sestamibi
      dual-isotope myocardial SPECT.
AB  - Myocardial perfusion scintigraphy is an established method in cardiology for the
      diagnosis and evaluation of coronary artery disease (CAD). Thallium-201 and Tc
      99m sestamibi myocardial perfusion imaging has been widely accepted as non
      invasive diagnostic procedure for detection of CAD, risk stratification and
      myocardial viability assessment. But, standard Tl-201 redistribution and same day
      or 2-day rest/stress Tc-99m sestamibi protocols are time-consuming. Hence, the
      dual isotope rest thallium-201/stress technetium-99m sestamibi gated single
      photon emission tomography protocol has gained increasing popularity for these
      applications. Combining the use of thallium-201 with technetium-99m agents
      permits optimal image resolution and simultaneous assessment of viability. Dual
      isotope imaging may be separate or simultaneous acquisition set-up. The more
      rapid completion of these studies is appreciated as an advantage by patients,
      technologists, interpreting and referring physicians, nurses and hospital
      management. Simultaneous imaging has the potential advantages of precise pixel
      registration and artifacts, if present, are identical in both thallium and
      sestamibi, and require only one set of imaging. Also, there are some
      disadvantages of spillover of activity from the Tc-99m to the Tl-201 window.
      Fortunately, despite this problem it can be overcome. Separate acquisition dual
      isotope also has some disadvantages. Difference in defect resolution in
      attenuation and scatter between T-201 and Tc-99m sestamibi potentially results in
      interpretation problems. But, studies about cost-effectiveness of dual isotope
      imaging showed that some selective elimination of the rest studies may decrease
      the cost of the nuclear procedures and should be considered in the current care
      health system.

PMID- 15165952
TI  - [The role of aerobic exercise following myocardial infarction].
AB  - Aerobic exercise training has an important role within the cardiac rehabilitation
      program. An exercise test performed in the early period after myocardial
      infarction (MI) allows determining early the functional status and the risk
      factors of the patients and can accelerate their return to their occupational
      life. Patients can get back faster and safely to their active lifestyle following
      MI with exercises carried out at least 3 days per week, for 20 to 60 minutes and
      at intensities between 40% to 85% of VO2max. These exercises may concern the
      lower extremity like walking or running, upper extremity like arm cycle ergometer
      or combinations of these like rowing or swimming. Regular aerobic exercises
      increase the functional capacity and parasympathetic tone, and these together
      lead to an improvement in cardiovascular autonomic control. As a result,
      frequency of coronary artery disease and other cardiovascular diseases declines
      to an important extent. Studies conducted in humans and animals have shown
      contradictory outcomes about left ventricular remodelling. General opinion is
      that aerobic exercise has no favourable effect on ventricular remodelling.

PMID- 15165954
TI  - [Diagnosis and treatment of ischemic mitral regurgitation].

PMID- 15165955
TI  - Supraannular mitral valve replacement in a child with congenital mitral stenosis.

PMID- 15165956
TI  - Middle aortic syndrome as a cause of dilated cardiomyopathy.

PMID- 15165957
TI  - Sinus node deceleration during exercise stress testing: Bezold-Jarisch reflex
      versus sinus node ischemia.

PMID- 15165958
TI  - Pulmonary right-upper lobar arteriovenous fistula in an infant with progressive
      cyanosis.

PMID- 15165959
TI  - [Two mitral stenosis cases without anticoagulant therapy with signs of left
      atrial thrombus].

PMID- 15165960
TI  - [Terminological chaos in cardiopulmonary exercise tests].

PMID- 15165961
TI  - [The right ventricular outflow tract reconstruction with "Contegra VenPro"
      heterologous conduit in the Ross procedure].

PMID- 15165962
TI  - A giant left main coronary artery aneurysm in a patient with Behcet's Disease.

PMID- 15165963
TI  - [Coronary artery abnormality: Congenital absence of left circumflex coronary
      artery].

PMID- 15165964
TI  - Single coronary artery arising from the right sinus of Valsalva.

PMID- 15165965
TI  - Multiple complications in a patient with acute myocardial infarction.

PMID- 15165966
TI  - More on competency-based education.

PMID- 15165967
TI  - Assessing competence in communication and interpersonal skills: the Kalamazoo II
      report.
AB  - Accreditation of residency programs and certification of physicians requires
      assessment of competence in communication and interpersonal skills. Residency and
      continuing medical education program directors seek ways to teach and evaluate
      these competencies. This report summarizes the methods and tools used by
      educators, evaluators, and researchers in the field of physician-patient
      communication as determined by the participants in the "Kalamazoo II" conference
      held in April 2002. Communication and interpersonal skills form an integrated
      competence with two distinct parts. Communication skills are the performance of
      specific tasks and behaviors such as obtaining a medical history, explaining a
      diagnosis and prognosis, giving therapeutic instructions, and counseling.
      Interpersonal skills are inherently relational and process oriented; they are the
      effect communication has on another person such as relieving anxiety or
      establishing a trusting relationship. This report reviews three methods for
      assessment of communication and interpersonal skills: (1) checklists of observed
      behaviors during interactions with real or simulated patients; (2) surveys of
      patients' experience in clinical interactions; and (3) examinations using oral,
      essay, or multiple-choice response questions. These methods are incorporated into
      educational programs to assess learning needs, create learning opportunities, or
      guide feedback for learning. The same assessment tools, when administered in a
      standardized way, rated by an evaluator other than the teacher, and using a
      predetermined passing score, become a summative evaluation. The report summarizes
      the experience of using these methods in a variety of educational and evaluation
      programs and presents an extensive bibliography of literature on the topic.
      Professional conversation between patients and doctors shapes diagnosis,
      initiates therapy, and establishes a caring relationship. The degree to which
      these activities are successful depends, in large part, on the communication and
      interpersonal skills of the physician. This report focuses on how the physician's
      competence in professional conversation with patients might be measured. Valid,
      reliable, and practical measures can guide professional formation, determine
      readiness for independent practice, and deepen understanding of the communication
      itself.

PMID- 15165968
TI  - Satisfying the patient, but failing the test.
AB  - Communication experts convened in Kalamazoo, Michigan, in 2002 to assess current
      tools that evaluate physician communication skills. They noted occasional
      discrepancies between a patient's impression of a physician's skill and the
      physician's performance as measured by current checklists. The authors explore
      the reasons for this discrepancy and propose a research agenda to resolve it.
      They maintain that the patient's evaluation of physician communication skills
      depends upon the degree to which the patient's reason for seeking care is
      satisfied. Since current evaluation tools do not incorporate information to which
      only the patient has access, they can assess neither the meaning of the interview
      nor the success of the physician from the patient's point of view. The authors
      conclude that physicians' understanding of how well they are meeting patients'
      needs may require competencies that are unmeasured or only partially measured by
      current assessment tools, such as "flexibility" or "improvisational skills."
      These competencies likely reside in the nonverbal domain. The authors suggest
      that (1) a new tool must be developed that measures the essence, or meaning, of
      the visit from the patient's perspective; (2) this tool must incorporate
      information derived directly from the patient; and (3) research is needed to
      define those physician and patient behaviors that facilitate meaningful
      encounters.

PMID- 15165970
TI  - Teaching communication in clinical clerkships: models from the macy initiative in
      health communications.
AB  - Medical educators have a responsibility to teach students to communicate
      effectively, yet ways to accomplish this are not well-defined. Sixty-five percent
      of medical schools teach communication skills, usually in the preclinical years;
      however, communication skills learned in the preclinical years may decline by
      graduation. To address these problems the New York University School of Medicine,
      Case Western Reserve University School of Medicine, and the University of
      Massachusetts Medical School collaborated to develop, establish, and evaluate a
      comprehensive communication skills curriculum. This work was funded by the Josiah
      P. Macy, Jr. Foundation and is therefore referred to as the Macy Initiative in
      Health Communication. The three schools use a variety of methods to teach third
      year students in each school a set of effective clinical communication skills. In
      a controlled trial this cross-institutional curriculum project proved effective
      in improving communication skills of third-year students as measured by a
      comprehensive, multistation, objective structured clinical examination. In this
      paper the authors describe the development of this unique, collaborative
      initiative. Grounded in a three-school consensus on the core skills and critical
      components of a communication skills curriculum, this article illustrates how
      each school tailored the curriculum to its own needs. In addition, the authors
      discuss the lessons learned from conducting this collaborative project, which may
      provide guidance to others seeking to establish effective cross-disciplinary
      skills curricula.

PMID- 15165971
TI  - Core competencies in integrative medicine for medical school curricula: a
      proposal.
AB  - The authors present a set of curriculum guidelines in integrative medicine for
      medical schools developed during 2002 and 2003 by the Education Working Group of
      the Consortium of Academic Health Centers for Integrative Medicine (CAHCIM) and
      endorsed by the CAHCIM Steering Committee in May 2003. CAHCIM is a consortium of
      23 academic health centers working together to help transform health care through
      rigorous scientific studies, new models of clinical care, and innovative
      educational programs that integrate biomedicine, the complexity of human beings,
      the intrinsic nature of healing, and the rich diversity of therapeutic systems.
      Integrative medicine can be defined as an approach to the practice of medicine
      that makes use of the best-available evidence taking into account the whole
      person (body, mind, and spirit), including all aspects of lifestyle. It
      emphasizes the therapeutic relationship and makes use of both conventional and
      complementary/alternative approaches. The competencies described in this article
      delineate the values, knowledge, attitudes, and skills that CAHCIM believes are
      fundamental to the field of integrative medicine. Many of these competencies
      reaffirm humanistic values inherent to the practice of all medical specialties,
      while others are more specifically relevant to the delivery of the integrative
      approach to medical care, including the most commonly used
      complementary/alternative medicine modalities, and the legal, ethical,
      regulatory, and political influences on the practice of integrative medicine. The
      authors also discuss the specific challenges likely to face medical educators in
      implementing and evaluating these competencies, and provide specific examples of
      implementation and evaluation strategies that have been found to be successful at
      a variety of CAHCIM schools.

PMID- 15165972
TI  - Creating a learning environment to produce competent residents: the roles of
      culture and context.
AB  - Six core competencies have been developed for use by residency programs in
      assessing individual resident training outcomes. The authors propose that it is
      important to consider the role of residency culture and work context in helping
      residents achieve the required competencies. Specifically, the development of a
      learning-oriented culture and favorable work conditions that facilitate the
      presence of that culture should be a high priority for residency programs and the
      organizations (e.g., hospitals) in which they are housed. This places formal
      accountability at the doorstep of these programs and organizations in helping to
      create a "competent" resident. Using ideas from management theory, the authors
      identify specific attitudes, behaviors, and interactions that define a learning
      culture and show their usefulness when applied to residents' achievement of the
      competencies. They assert that current features of everyday resident work life
      decrease the chances that such attitudes, behaviors, and interactions will occur.
      Identifying and prioritizing the components of desired work environments for
      promoting a learning-oriented culture, in addition to assessing the presence or
      absence of both the components and learning best practices within residency
      programs, should become normal activities that complement the process of
      assessing competencies.

PMID- 15165973
TI  - More training needed in chronic care: a survey of US physicians.
AB  - PURPOSE: Although more than 125 million North Americans have one or more chronic
      conditions, medical training may not adequately prepare physicians to care for
      them. The authors evaluated physicians' perceptions of the adequacy of their
      chronic illness care training to and the effects of training on their attitudes
      toward care of persons with chronic conditions. METHOD: In November 2000 through
      June 2001, the authors surveyed by telephone a random sample of U.S. physicians
      who had > or =20 hours of patient contact per week. The interview instrument
      examined demographics, career satisfaction, practice characteristics, perceived
      adequacy of chronic illness care training in ten competencies (geriatric
      syndromes, chronic pain, nutrition, developmental milestones, end-of-life care,
      psychosocial issues, patient education, assessment of caregiver needs,
      coordination of services, and interdisciplinary teamwork), and effect of training
      on attitudes toward chronic illness care. RESULTS: Of 1,905 eligible physicians,
      1,236 (65%) responded (270 family or general practitioners, 231 internists, 129
      pediatricians, 335 nonsurgical specialists, and 271 surgeons). Most physicians
      reported their chronic disease training was less than adequate for all ten
      competencies. Family practitioners were more likely (p <.05) to report adequate
      training in seven competencies compared with internists, and in two to four
      competencies when compared with pediatricians, nonsurgical specialists, or
      surgeons. Most physicians reported that training had a positive effect on
      attitudes toward care of people with chronic conditions, including the ability to
      make a difference in their lives (74-84%). CONCLUSIONS: Physicians perceived
      their medical training for chronic illness care was inadequate. Medical schools
      and residencies may need to modify curricula to better prepare physicians to
      treat the growing number of people with chronic conditions.

PMID- 15165974
TI  - Do global rating forms enable program directors to assess the ACGME competencies?
AB  - PURPOSE: In 1999 the Accreditation Council for Graduate Medical Education (ACGME)
      mandated that GME programs require their residents to be proficient in six
      general competencies. The purpose of this study was to ascertain whether an
      existing global rating form could be modified to assess these competencies.
      METHOD: A rating form covering 23 skills described in the ACGME competencies was
      developed. The directors of 92 specialty and subspecialty programs at Thomas
      Jefferson University Hospital and the Albert Einstein Medical Center in
      Philadelphia were asked to rate residents at the end of the 2001-02 and 2002-03
      academic years. RESULTS: Ratings for 1,295 of 1,367 (95%) residents were
      available. Residents were awarded the highest mean ratings on items tied to
      professionalism, compassion, and empathy. The lowest mean ratings were assigned
      for items related to consideration of costs in care and management of resources.
      Factor analysis indicated that the program directors viewed overall competence in
      two dimensions of medical knowledge and interpersonal skills. This factor
      structure was stable for groups of specialties, and residents' gender and
      training level. Mean ratings in each dimension were progressively higher for
      residents at advanced levels of training. CONCLUSION: Global rating forms, the
      tool that program directors use most frequently to document residents'
      competence, may not be adequate to assess the six general competencies. The
      results are consistent with earlier published research indicating that physicians
      view competence in just two broad dimensions, which questions the premise of the
      six ACGME competencies. Further research is needed to validate and measure six
      distinct dimensions of clinical competence.

PMID- 15165975
TI  - Using the Federated Council for Internal Medicine curricular guide and
      administrative codes to assess IM residents' breadth of experience.
AB  - PURPOSE: To estimate internal medicine residents' breadth of experience using a
      published curricular guide and an electronic medical record. METHOD: A cohort of
      41 internal medicine residents at Columbia University Medical Center, a large,
      inner-city, primary and tertiary care center, were followed over their three
      years of training in the late 1990s. Residents were mapped to the patients they
      cared for, the diagnoses those patients were assigned, and the Federated Council
      for Internal Medicine (FCIM) competencies covered. The proportion and
      distribution of competencies covered (potential to achieve a competency) were
      measured. RESULTS: Residents covered 76% of priority 1 competencies (those
      identified by FCIM as optimally learned through direct responsibility for
      patients) and 67% of all competencies. Although the number of patients cared for
      was correlated with breadth of experience, the effect was small. Rare diagnoses
      appear to have been distributed well. CONCLUSION: Internal medicine residents had
      the potential to achieve the majority of competencies via direct patient care,
      but no residents achieved full coverage. The electronic medical record may
      provide a mechanism to track residents and study training programs.

PMID- 15165976
TI  - Assessing residents' competencies at baseline: identifying the gaps.
AB  - PURPOSE: Entering residents have variable medical school experiences and
      differing knowledge and skill levels. To structure curricula, enhance patient
      safety, and begin to meet accreditation requirements, baseline assessment of
      individual resident's knowledge and skills is needed. To this end, in 2001 the
      University of Michigan Health System created the Postgraduate Orientation
      Assessment (POA), an eight-station, objective structured clinical examination for
      incoming residents. METHOD: The POA, administered at orientation, included items
      addressing critical laboratory values, cross-cultural communication, evidence
      based medicine, radio-graphic image interpretation, informed consent, pain
      assessment and management, aseptic technique, and system compliance such as fire
      safety. The POA assessed many of the skills needed by interns in their initial
      months of training when supervision by senior physicians might not be present.
      RESULTS: In 2002, 132 interns from 14 different specialties and 59 different
      schools participated in the POA. The mean score was 74.8% (SD = 5.8). When scores
      were controlled for U.S. Medical Licensing Examination scores, there were no
      significant differences in performance across specialties. There were differences
      between University of Michigan Medical School graduates and those from other
      institutions (p <.001). Eighty-one percent of the residents would recommend the
      POA. CONCLUSIONS: The POA provides a feasible format to measure initial knowledge
      and skills and identify learning needs. Orientation is an effective time to
      identify important gaps in learning between medical school and residency. This is
      the first step in a continuing evaluation of the Accreditation Council for
      Graduate Medical Education's general competencies.

PMID- 15165977
TI  - The future-oriented department chair.
AB  - The authors describe the current dilemma facing academic health centers (AHCs) as
      they recruit department chairs. In the past, leaders at AHCs predominantly were
      concerned with fulfilling the esteemed tripartite missions of patient care,
      research, and education. Today, their time and energy are occupied by a different
      set of tasks that have a distinct business orientation, including winning
      contracts, enhancing revenue, reducing costs, recruiting and managing a diverse
      workforce, and dealing with consumer satisfaction and marketing. New visions and
      strategies must be developed--requiring different dimensions of leadership. The
      authors offer concrete recommendations for recruiting, retaining, and sustaining
      department chairs, and argue that a deliberative, thoughtful process of engaging
      chair candidates should begin by focusing on the candidates' values as a first
      priority. Candidates who most clearly share organizational values should then be
      engaged in an iterative process of developing a shared vision, resulting in a
      letter of agreement that explicitly states the mutual expectations and
      commitments of both the organization and the candidate. Once department chairs
      are in place, ongoing development through leadership training, mentoring, and
      other investments help to retain and sustain them.

PMID- 15165978
TI  - The art of death and dying: medical education in the Metropolitan Museum of Art's
      Egyptian art galleries.

PMID- 15165980
TI  - Computer use among community-based primary care physician preceptors.
AB  - PURPOSE: Use of the Internet to access biomedical information in patient care has
      important implications in medical education. Little is known about how community
      based clinical teachers use computers in their offices and what factors, such as
      age, may influence use. METHOD: A total of 178 active community-based primary
      care preceptors were mailed a 15-item questionnaire about their computer
      equipment; Internet use; and specific applications in patient care, patients'
      education, medical students' or residents' education, or accessing other clinical
      and/or research information. Data analysis used descriptive statistics, chi
      square for comparisons of categorical data and analysis of variance (ANOVA) mixed
      model for comparisons of continuous variables. All tests were two-tailed with
      alpha set at.05 to determine statistical significance. RESULTS: In all, 129
      preceptors responded (73%). Office computer availability was high (92%). The
      Internet as a clinical information resource was used most frequently (98%) and MD
      Consult and Medline-EBM were used less frequently (20% and 21%, respectively). No
      statistical differences were found in routine use by age of preceptor; frequency
      of use did differ. Preceptors 60 years or older were four times more likely to
      use the Internet to assist in students' and residents' education (p =.02) and at
      least twice as likely to use full text Medline articles for patient care
      decisions (p =.05) than their younger colleagues. Decreased computer use was
      related to lack of time (45%) or other logistical reasons (40%), such as the
      computer's distance from the patient care areas or slow connections. CONCLUSIONS:
      Rates of computer access and Internet connectivity were high among community
      based preceptors of all ages. Uses of specific online clinical and/or educational
      resources varied by preceptors' age with more rather than less use among older
      preceptors, an unexpected finding.

PMID- 15165981
TI  - Internal medicine-pediatrics residency training: current program trends and
      outcomes.
AB  - PURPOSE: Combined internal medicine-pediatrics (med-peds) residency programs have
      existed since 1967. Due to the rapid growth in the number and size of programs
      during the 1990s, most current med-peds physicians completed their residency in
      the last ten years, making older studies of med-peds programs obsolete. The
      authors sought to determine completion rates of med-peds residency programs and
      describe the initial career plans for five cohorts of graduating residents from
      combined med-peds training programs. METHOD: Program directors of all U.S. med
      peds residency programs were asked to complete a Web-based survey and base their
      responses on the records of cohorts of residents completing their programs from
      1998 through 2002. To allow sufficient time to complete both the American Board
      of Pediatrics (ABP) and American Board of Internal Medicine (ABIM) certification
      examinations, certification status was requested only for the cohort completing
      training in 1998. RESULTS: Responses were obtained from 92% (83/90) of the
      programs, reflecting 1,595 residents entering med-peds programs. Of these
      residents, 91% graduated from a med-peds program. Among the graduates, 82% were
      seeing both adults and children, 22% went on to subspecialty residencies, 21%
      began practice in rural or underserved areas, and 25% entered an academic
      position. ABIM and ABP pass rates for the 1998 cohort were 97% and 96%,
      respectively. Overall, 79% of the 1998 graduates are board certified in both
      specialties. CONCLUSIONS: Compared with previous studies, a greater proportion of
      residents who recently entered med-peds programs completed their dual training,
      and a larger percentage of graduates are seeing both adults and children. The
      proportion of residents entering subspecialty residencies has increased
      significantly, but the proportion of graduates in academic careers has remained
      stable.

PMID- 15165983
TI  - The relationship between interviewers' characteristics and ratings assigned
      during a multiple mini-interview.
AB  - PURPOSE: To assess the consistency of ratings assigned by health sciences faculty
      members relative to community members during an innovative admissions protocol
      called the Multiple Mini-Interview (MMI). METHOD: A nine-station MMI was created
      and 54 candidates to an undergraduate MD program participated in the exercise in
      Spring 2003. Three stations were staffed with a pair of faculty members, three
      with a pair of community members, and three with one member of each group. Raters
      completed a four-item evaluation form. All participants completed post-MMI
      questionnaires. Generalizability Theory was used to examine the consistency of
      the ratings provided within each of these three subgroups. RESULTS: The overall
      test reliability was found to be .78 and a Decision Study suggested that
      admissions committees should distribute their resources by increasing the number
      of interviews to which candidates are exposed rather than increasing the number
      of interviewers within each interview. Divergence of ratings was greater within
      the pairing of community member to faculty member and least for pairings of
      community members. Participants responded positively to the MMI. CONCLUSION: The
      MMI provides a reliable protocol for assessing the personal qualities of
      candidates by accounting for context specificity with a multiple sampling
      approach. Increasing the heterogeneity of interviewers may increase the
      heterogeneity of the accepted group of candidates. Further work will determine
      the extent to which different groups of raters provide equally valid (albeit
      different) judgments.

PMID- 15165982
TI  - The influence of testing context and clinical rotation order on students' OSCE
      performance.
AB  - PURPOSE: To investigate the influence of testing context and rotation order on
      third-year medical student performance on a common objective structured clinical
      examination (OSCE) station in both obstetrics-gynecology (ob-gyn) and psychiatry
      rotations. METHOD: Archival OSCE performance data (in the form of a 25-item
      binary content checklist) from one class of third-year medical students (n = 141)
      at Saint Louis University (2002-03) were aggregated and analyzed. RESULTS:
      Despite the fact that the station was identical in both OSCEs, students were, in
      general, less likely to inquire about ob-gyn issues on the psychiatry OSCE and
      less likely to inquire about psychiatric issues on the ob-gyn OSCE, regardless of
      order of rotation. Order did have a positive effect on some results, such that
      students were more likely to mention menopause and vaginal dryness on the
      psychiatry OSCE if they had already had the ob-gyn rotation. CONCLUSION: The
      testing context may influence student approaches to patients in ways that bias
      their collection and interpretation of information. OSCE evaluations may better
      approximate true clinical context and complexity by presenting case scenarios
      that reflect a broader range of diagnostic possibilities than those limited to
      the recently completed rotation.

PMID- 15165984
TI  - Results of the National Resident Matching Program for 2004.

PMID- 15165985
TI  - Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell
      shortening in adult rat cardiomyocytes.
AB  - The Na(+)/Ca(2+) exchanger (NCX) may influence cardiac function depending on its
      predominant mode of action, forward mode or reverse mode, during the contraction
      relaxation cycle. The intracellular Na(+) concentration ([Na(+)](i)) and the
      duration of the action potential as well as the level of NCX protein expression
      regulate the mode of action of NCX. [Na(+)](i) and NCX expression have been
      reported to be increased in human heart failure. Nevertheless, the consequences
      of altered NCX expression in heart failure are still a matter of discussion. We
      aimed to characterize the influence of NCX expression on intracellular Ca(2+)
      transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to
      ninefold (dose dependent) overexpression of NCX protein was achieved after 48 h
      by somatic gene transfer (Ad.NCX.GFP) versus control (Ad.GFP). NCX activity,
      determined by Na(+) gradient-dependent (45)Ca(2+)-uptake, was significantly
      increased. The protein expressions of sarco(endo)plasmic reticulum Ca(2+)-ATPase,
      phospholamban, and calsequestrin were unaffected by NCX overexpression.
      Fractional shortening (FS) of isolated cardiomyocytes was significantly increased
      at low stimulation rates in Ad.NCX.GFP. After a step-wise enhancing frequency of
      stimulation to 3.0 Hz, FS remained unaffected in Ad.GFP cells but declined in
      Ad.NCX.GFP cells. The positive inotropic effect of the cardiac glycoside ouabain
      was less effective in Ad.NCX.GFP cells, whereas the positive inotropic effect of
      beta-adrenergic stimulation remained unchanged. In conclusion, NCX overexpression
      results in a reduced cell shortening at higher stimulation frequencies as well as
      after inhibition of sarcolemmal Na(+)-K(+)-ATPase, i.e., in conditions with
      enhanced [Na(+)](i). At low stimulation rates, increased NCX expression enhances
      both intracellular systolic Ca(2+) and contraction amplitude.

PMID- 15165986
TI  - Cell transplantation for treatment of acute myocardial infarction: unique
      capacity for repair by skeletal muscle satellite cells.
AB  - An adult heart injured by an ischemic episode has a limited capacity to
      regenerate. We administered three types of adult guinea pig cells [cardiomyocytes
      (CMs), cardiac fibroblasts (CFs), and skeletal myoblasts (Mbs)] to compare their
      suitability for repair of acute myocardial infarction. We used confocal
      fluorescent microscopy and a variety of specific immunomarkers and
      echocardiography to provide anatomic evidence for the viability of such cells and
      their possible functional beneficial effects. All cells were transfected with
      adenovirus-containing beta-galactosidase gene so that migration from the
      injection sites could be traced. Both freshly isolated CMs as well as CFs were
      found concentrated in the infarcted zone; these cells survived for at least 2 wk
      posttransplantation. Transplanted CMs were regularly striated and grew long
      projections that could form gap junctions with native CMs, which was evidenced by
      connexin43 labeling. In addition, CM transplantation resulted in increased
      angiogenesis in the infarcted areas. In contrast, transplanted CFs did not appear
      to make any gap junctional contacts with native CMs nor did they enhance local
      angiogenesis. Mbs cultured for 7 days and transfected Mbs were identified 7 days
      posttransplantation in the infarcted area. During that time and thereafter, Mbs
      proliferated and differentiated into myotubes that formed new, regularly striated
      myofibers that occupied most (50-70%) of the infarcted area by 2-3 wk. These
      newly formed myofibers maintained their Mb skeletal muscle origin as evidenced by
      their capacity to express myogenin and fast skeletal myosin. This skeletal
      phenotype appeared to downregulate with time, and Mbs partially
      transdifferentiated into a cardiac phenotype as indicated by labeling for cardiac
      specific troponin T and cardiac myosin heavy chain. By the third week
      posttransplantation, new myofibers formed apparent contacts with the native CMs
      via putative gap junctions that expressed connexin43. Myocardial performance of
      animals that were successfully transplanted with Mbs was improved.

PMID- 15165987
TI  - 5-HT-mediated inhibition of cardiovagal baroreceptor reflex response during
      defense reaction in the rat.
AB  - Previous studies showed that the cardiac response of the baroreceptor reflex
      (bradycardia) is inhibited during the defense reaction evoked by direct
      electrical or chemical stimulation of the periaqueductal gray (dPAG) in the rat.
      Whether central serotonin and nucleus tractus solitarius (NTS) serotonin(3) (5
      HT(3)) receptors might participate in this inhibition was investigated in
      urethane-anesthetized and atenolol-pretreated rats. Our results showed that both
      electrical and chemical stimulation of the dPAG produced a drastic reduction of
      the cardiovagal component of the baroreceptor reflex triggered by either
      intravenous administration of phenylephrine or aortic nerve stimulation. This
      inhibitory effect of dPAG stimulation on the baroreflex bradycardia was not
      observed in rats that had been pretreated with p-chlorophenylalanine (300 mg/kg
      ip daily for 3 days) to inhibit serotonin synthesis. Subsequent 5
      hydroxytryptophan administration (60 mg/kg ip), which was used to restore
      serotonin synthesis, allowed the inhibitory effect of dPAG stimulation on both
      aortic and phenylephrine-induced cardiac reflex responses to be recovered in p
      chlorophenylalanine-pretreated rats. On the other hand, in nonpretreated rats,
      the inhibitory effect of dPAG stimulation on the cardiac baroreflex response
      could be markedly reduced by prior intra-NTS microinjection of granisetron, a 5
      HT(3) receptor antagonist, or bicuculline, a GABA(A) receptor antagonist. These
      results show that serotonin plays a key role in the dPAG stimulation-induced
      inhibition of the cardiovagal baroreceptor reflex response. Moreover, they
      support the idea that 5-HT(3) and GABA(A) receptors in the NTS contribute
      downstream to the inhibition of the baroreflex response caused by dPAG
      stimulation.

PMID- 15165988
TI  - Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in humans.
AB  - Previous studies have provided evidence of a non-noradrenergic contributor to
      reflex cutaneous vasoconstriction in humans but did not identify the transmitter
      responsible. To test whether neuropeptide Y (NPY) has a role, in two series of
      experiments we slowly reduced whole body skin temperature (TSK) from 34.5 to 31.7
      degrees C. In protocol 1, Ringer solution and the NPY receptor antagonist BIBP
      3226 alone were delivered intradermally via microdialysis. In protocol 2,
      yohimbine plus propranolol (Yoh + Pro), Yoh + Pro in combination with BIBP-3226,
      and Ringer solution were delivered to antagonize locally the vasomotor effects of
      NPY and norepinephrine. Blood flow was measured by laser Doppler flowmetry (LDF).
      Mean arterial blood pressure (MAP) was monitored at the finger (Finapres). In
      protocol 1, cutaneous vascular conductance (CVC) fell by 45%, to 55.1 +/- 5.6% of
      baseline at control sites (P < 0.05). At BIBP-3226-treated sites, CVC fell by
      34.1% to 65.9 +/- 5.0% (P < 0.05; P < 0.05 between sites). In protocol 2, during
      body cooling, CVC at control sites fell by 32.6%, to 67.4 +/- 4.3% of baseline;
      at sites treated with Yoh + Pro, CVC fell by 18.7%, to 81.3 +/- 4.4% of baseline
      (P < 0.05 vs. baseline; P < 0.05 vs. control) and did not fall significantly at
      sites treated with BIBP-3226 + Yoh + Pro (P > 0.05; P < 0.05 vs. other sites).
      After cooling, exogenous norepinephrine induced vasoconstriction at control sites
      (P < 0.05) but not at sites treated with Yoh + Pro + BIBP-3226 (P > 0.05). These
      results indicate that NPY participates in sympathetically mediated cutaneous
      vasoconstriction in humans during whole body cooling.

PMID- 15165989
TI  - Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a
      caspase-3-independent pathway.
AB  - Reperfusion-induced oxidative injury to the myocardium promotes activation and
      proliferation of cardiac fibroblasts and repair by scar formation. Osteopontin
      (OPN) is a proinflammatory cytokine that is upregulated after reperfusion. To
      determine whether OPN enhances fibroblast survival after exposure to oxidants,
      cardiac fibroblasts from wild-type (WT) or OPN-null (OPN(-/-)) mice were treated
      in vitro with H(2)O(2) to model reperfusion injury. Within 1 h, membrane
      permeability to propidium iodide (PI) was increased from 5 to 60% in OPN(-/-)
      cells but was increased to only 20% in WT cells. In contrast, after 1-8 h of
      treatment with H(2)O(2), the percent of terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL)-stained cells was more than twofold
      higher in WT than OPN(-/-) cells. Electron microscopy of WT cells treated with
      H(2)O(2) showed chromatin condensation, nuclear fragmentation, and cytoplasmic
      and nuclear shrinkage, which are consistent with apoptosis. In contrast, H(2)O(2)
      treated OPN(-/-) cardiac fibroblasts exhibited cell and nuclear swelling and
      membrane disruption that are indicative of cell necrosis. Treatment of OPN(-/-)
      and WT cells with a cell-permeable caspase-3 inhibitor reduced the percentage of
      TUNEL staining by more than fourfold in WT cells but decreased staining in OPN(-/
      ) cells by approximately 30%. Although the percentage of PI-permeable WT cells
      was reduced threefold, the percent of PI-permeable OPN(-/-) cells was not
      altered. Restoration of OPN expression in OPN(-/-) fibroblasts reduced the
      percentage of PI-permeable cells but not TUNEL staining after H(2)O(2) treatment.
      Thus H(2)O(2)-induced cell death in OPN-deficient cardiac fibroblasts is mediated
      by a caspase-3-independent, necrotic pathway. We suggest that the increased
      expression of OPN in the myocardium after reperfusion may promote fibrosis by
      protecting cardiac fibroblasts from cell death.

PMID- 15165990
TI  - Expression of cardiac troponin T with COOH-terminal truncation accelerates cross
      bridge interaction kinetics in mouse myocardium.
AB  - Transgenic mice expressing an allele of cardiac troponin T (cTnT) with a COOH
      terminal truncation (cTnT(trunc)) exhibit severe diastolic and mild systolic
      dysfunction. We tested the hypothesis that contractile dysfunction in myocardium
      expressing low levels of cTnT(trunc) (i.e., <5%) is due to slowed cross-bridge
      kinetics and reduced thin filament activation as a consequence of reduced cross
      bridge binding. We measured the Ca(2+) sensitivity of force development [pCa for
      half-maximal tension generation (pCa(50))] and the rate constant of force
      redevelopment (k(tr)) in cTnT(trunc) and wild-type (WT) skinned myocardium both
      in the absence and in the presence of a strong-binding, non-force-generating
      derivative of myosin subfragment-1 (NEM-S1). Compared with WT mice, cTnT(trunc)
      mice exhibited greater pCa(50), reduced steepness of the force-pCa relationship
      [Hill coefficient (n(H))], and faster k(tr) at submaximal Ca(2+) concentration
      ([Ca(2+)]), i.e., reduced activation dependence of k(tr). Treatment with NEM-S1
      elicited similar increases in pCa(50) and similar reductions in n(H) in WT and
      cTnT(trunc) myocardium but elicited greater increases in k(tr) at submaximal
      activation in cTnT(trunc) myocardium. Contrary to our initial hypothesis,
      cTnT(trunc) appears to enhance thin filament activation in myocardium, which is
      manifested as significant increases in Ca(2+)-activated force and the rate of
      cross-bridge attachment at submaximal [Ca(2+)]. Although these mechanisms would
      not be expected to depress systolic function per se in cTnT(trunc) hearts, they
      would account for slowed rates of myocardial relaxation during early diastole.

PMID- 15165991
TI  - FFAs are not involved in regulation of gluconeogenesis and glycogenolysis in
      adults with uncomplicated P. falciparum malaria.
AB  - In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates
      gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with
      uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased.
      To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated
      falciparum malaria, we investigated the effect of inhibition of lipolysis by
      acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were
      given acipimox, and six served as controls. Also as controls, six matched healthy
      subjects were studied on two occasions with and without acipimox. After 16 h of
      fasting, glucose production and GNG were significantly higher in the malaria
      patients compared with the healthy controls (P = 0.003 and < 0.0001,
      respectively), whereas GLY was significantly lower (P < 0.001), together with
      elevated plasma concentrations of cortisol and glucagon. During the study,
      glucose production in patients declined over time (P < 0.0001), without a
      statistically significant difference between the acipimox-treated and untreated
      patients. In controls, however, with acipimox the decline was less outspoken
      compared with nontreated controls (P = 0.005). GNG was unchanged over time in
      patients as well as in healthy controls, and no influence of acipimox was found.
      In patients, GLY declined over time (P < 0.001), without a difference between
      acipimox-treated and untreated patients. In contrast, in controls treated with
      acipimox, no change over time was found, which was statistically different from
      the decline in untreated controls (P = 0.002). In conclusion, in falciparum
      malaria, FFAs are not involved in regulation of glucose production, nor of GNG or
      GLY.

PMID- 15165992
TI  - AMP kinase is not required for the GLUT4 response to exercise and denervation in
      skeletal muscle.
AB  - An acute bout of exercise increases muscle GLUT4 mRNA in mice, and denervation
      decreases GLUT4 mRNA. AMP-activated protein kinase (AMPK) activity in skeletal
      muscle is also increased by exercise, and GLUT4 mRNA is increased in mouse
      skeletal muscle after treatment with AMPK activator 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside(AICAR). These findings suggest that AMPK
      activation might be responsible for the increase in GLUT4 mRNA expression in
      response to exercise. To investigate the role of AMPK in GLUT4 regulation in
      response to exercise and denervation, transgenic mice with a mutated AMPK alpha
      subunit (dominant negative; AMPK-DN) were studied. GLUT4 did not increase in AMPK
      DN mice that were treated with AICAR, demonstrating that muscle AMPK is inactive.
      Exercise (two 3-h bouts of treadmill running separated by 1 h of rest) increased
      GLUT4 mRNA in both wild-type and AMPK-DN mice. Likewise, denervation decreased
      GLUT4 mRNA in both wild-type and AMPK-DN mice. GLUT4 mRNA was also increased by
      AICAR treatment in both the innervated and denervated muscles. These data
      demonstrate that AMPK is not required for the response of GLUT4 mRNA to exercise
      and denervation.

PMID- 15165994
TI  - Regulation of full-length and truncated growth hormone (GH) receptor by GH in
      tissues of lit/lit or bovine GH transgenic mice.
AB  - Two truncated isoforms of growth hormone (GH) receptor (GHR) were identified in
      mice and in humans. The proteins encoded by these isoforms lack most of the
      intracellular domain of the GHR and inhibit GH action in a dominant negative
      fashion. We have quantified the mRNAs encoding the GHR isoforms in mouse tissues
      by use of real-time RT-PCR and examined the effect of GH excess or deficiency on
      regulation of mRNA levels of the GHR isoforms in vivo. In the liver, the
      truncated GHR mRNAs (mGHR-282 and mGHR-280) were 0.5 and <0.1%, respectively, the
      level of full-length GHR (mGHR-fl). In skeletal muscle, the values were 2-3 and
      0.1-0.5% of mGHR-fl, respectively, and in subcutaneous fat, the values were 3-5
      and 0.1-0.5% of mGHR-fl, respectively. The bovine GH transgenic mice showed a
      significant increase of mGHR-fl in liver but a significant decrease in skeletal
      muscle, with no difference in subcutaneous fat when compared with control mice.
      The lit/lit mice showed a significant decrease of mGHR-fl in liver, no difference
      of mGHR-fl in muscle, and a significant increase of mGHR-fl in subcutaneous fat
      when compared with lit/+ mice. The mRNA of mGHR-282 was regulated in parallel
      with mGHR-fl in all tissues of all mice examined, whereas that of mGHR-280 was
      not changed in either GH-excess or GH-deficient states. In conclusion, two
      truncated isoforms of GHR mRNAs were detected in liver, skeletal muscle, and
      subcutaneous fat of mice. The ratio of GHR-tr to GHR-fl mRNA was tissue specific
      and not affected by chronic excess or deficiency of GH.

PMID- 15165993
TI  - Cold-induced PGC-1alpha expression modulates muscle glucose uptake through an
      insulin receptor/Akt-independent, AMPK-dependent pathway.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      participates in control of expression of genes involved in adaptive
      thermogenesis, muscle fiber type differentiation, and fuel homeostasis. The
      objective of the present study was to evaluate the participation of cold-induced
      PGC-1alpha expression in muscle fiber type-specific activity of proteins that
      belong to the insulin-signaling pathway. Rats were exposed to 4 degrees C for 4
      days and acutely treated with insulin in the presence or absence of an antisense
      oligonucleotide to PGC-1alpha. Cold exposure promoted a significant increase of
      PGC-1alpha and uncoupling protein-3 protein expression in type I and type II
      fibers of gastrocnemius muscle. In addition, cold exposure led to higher glucose
      uptake during a hyperinsulinemic clamp, which was accompanied by higher
      expression and membrane localization of GLUT4 in both muscle fiber types. Cold
      exposure promoted significantly lower insulin-induced tyrosine phosphorylation of
      the insulin receptor (IR) and Ser473 phosphorylation of acute transforming
      retrovirus thymoma (Akt) and an insulin-independent increase of Thr172
      phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK).
      Inhibition of PGC-1alpha expression in cold-exposed rats by antisense
      oligonucleotide treatment diminished glucose clearance rates during a
      hyperinsulinemic clamp and reduced expression and membrane localization of GLUT4.
      Reduction of PGC-1alpha expression resulted in no modification of insulin-induced
      tyrosine phosphorylation of the IR and Ser473 phosphorylation of Akt. Finally,
      reduction of PGC-1alpha resulted in lower Thr172 phosphorylation of AMPK. Thus
      cold-induced hyperexpression of PGC-1alpha participates in control of skeletal
      muscle glucose uptake through a mechanism that controls GLUT4 expression and
      subcellular localization independent of the IR and Akt activities but dependent
      on AMPK.

PMID- 15165996
TI  - Na+ -dependent neutral amino acid transporters A, ASC, and N of the blood-brain
      barrier: mechanisms for neutral amino acid removal.
AB  - Four Na+ -dependent transporters of neutral amino acids (NAA) are known to exist
      in the abluminal membranes (brain side) of the blood-brain barrier (BBB). This
      article describes the kinetic characteristics of systems A, ASC, and N that,
      together with the recently described Na+ -dependent system for large NAA (Na+ 
      LNAA), provide a basis for understanding the functional organization of the BBB.
      The data demonstrate that system A is voltage dependent (3 positive charges
      accompany each molecule of substrate). Systems ASC and N are not voltage
      dependent. Each NAA is a putative substrate for at least one system, and several
      NAA are transported by as many as three. System A transports Pro, Ala, His, Asn,
      Ser, and Gln; system ASC transports Ser, Gly, Met, Val, Leu, Ile, Cys, and Thr;
      system N transports Gln, His, Ser, and Asn; Na+ -LNAA transports Leu, Ile, Val,
      Trp, Tyr, Phe, Met, Ala, His, Thr, and Gly. Together, these four systems have the
      capability to actively transfer every naturally occurring NAA from the
      extracellular fluid (ECF) to endothelial cells and thence to the circulation. The
      existence of facilitative transport for NAA (L1) on both membranes provides the
      brain access to essential NAA. The presence of Na+ -dependent carriers on the
      abluminal membrane provides a mechanism by which NAA concentrations in the ECF of
      brain are maintained at approximately 10% of those of the plasma.

PMID- 15165995
TI  - Critical role of vitamin D in sulfate homeostasis: regulation of the sodium
      sulfate cotransporter by 1,25-dihydroxyvitamin D3.
AB  - As the fourth most abundant anion in the body, sulfate plays an essential role in
      numerous physiological processes. One key protein involved in transcellular
      transport of sulfate is the sodium-sulfate cotransporter NaSi-1, and previous
      studies suggest that vitamin D modulates sulfate homeostasis by regulating NaSi-1
      expression. In the present study, we found that, in mice lacking the vitamin D
      receptor (VDR), NaSi-1 expression in the kidney was reduced by 72% but intestinal
      NaSi-1 levels remained unchanged. In connection with these findings, urinary
      sulfate excretion was increased by 42% whereas serum sulfate concentration was
      reduced by 50% in VDR knockout mice. Moreover, levels of hepatic glutathione and
      skeletal sulfated proteoglycans were also reduced by 18 and 45%, respectively, in
      the mutant mice. Similar results were observed in VDR knockout mice after their
      blood ionized calcium levels and rachitic bone phenotype were normalized by
      dietary means, indicating that vitamin D regulation of NaSi-1 expression and
      sulfate metabolism is independent of its role in calcium metabolism. Treatment of
      wild-type mice with 1,25-dihydroxyvitamin D3 or vitamin D analog markedly
      stimulated renal NaSi-1 mRNA expression. These data provide strong in vivo
      evidence that vitamin D plays a critical role in sulfate homeostasis. However,
      the observation that serum sulfate and skeletal proteoglycan levels in
      normocalcemic VDR knockout mice remained low in the absence of rickets and
      osteomalacia suggests that the contribution of sulfate deficiency to development
      of rickets and osteomalacia is minimal.

PMID- 15165997
TI  - Modeling of lipid and protein depletion during total starvation.
AB  - This study presents a model describing lipid and protein depletion of an
      individual facing total starvation. The model distinguishes two compartments of
      body mass: a metabolic compartment and a structural compartment. It is considered
      that the lipids and the proteins of the metabolic compartment ensure the totality
      of physiological functions. The main assumptions of the model lie in the
      definitions of lipid mass and protein mass of the metabolic compartment, which
      are related to total lipid mass and total body mass, respectively. Under these
      assumptions, for a given individual, the ratio of lipid and protein utilization
      rates is proportional to the adiposity. The model accounts for the protein
      sparing observed at high adiposity levels and enables us to discuss the
      individual's survival in relation to the levels of lipid and protein depletion.
      The time course of changes in lipid and protein depletion rates can be calculated
      by introducing the energy expenditure of the individual. In simulations, it was
      assumed that specific energy expenditure was constant during starvation and that
      mortality occurred at a critical level of protein depletion. The most
      characteristic results derived from these simulations concern the kinetics of
      protein depletion, which depend markedly on initial adiposity. Accordingly, in
      obese subjects, the rate of protein losses remains fairly constant during
      fasting, whereas it increases from the onset of the fast in lean subjects, in
      agreement with experimental observations. In the model, protein and lipid
      depletion rates are both proportional to energy expenditure, which needs to be
      confirmed from complementary data.

PMID- 15165998
TI  - Intramyocellular lipid content in type 2 diabetes patients compared with
      overweight sedentary men and highly trained endurance athletes.
AB  - Recent evidence suggests that intramyocellular lipid (IMCL) accretion is
      associated with obesity and the development of insulin resistance and/or type 2
      diabetes. However, trained endurance athletes are markedly insulin sensitive,
      despite an elevated mixed muscle lipid content. In an effort to explain this
      metabolic paradox, we compared muscle fiber type-specific IMCL storage between
      populations known to have elevated IMCL deposits. Immunofluorescence microscopy
      was performed on muscle biopsies obtained from eight highly trained endurance
      athletes, eight type 2 diabetes patients, and eight overweight, sedentary men
      after an overnight fast. Mixed muscle lipid content was substantially greater in
      the endurance athletes (4.0 +/- 0.4% area lipid stained) compared with the
      diabetes patients and the overweight men (2.3 +/- 0.4 and 2.2 +/- 0.5%,
      respectively). More than 40% of the greater mixed muscle lipid content was
      attributed to a higher proportion type I muscle fibers (62 +/- 8 vs. 38 +/- 3 and
      33 +/- 7%, respectively), which contained 2.8 +/- 0.3-fold more lipid than the
      type II fibers. The remaining difference was explained by a significantly greater
      IMCL content in the type I muscle fibers of the trained athletes. Differences in
      IMCL content between groups or fiber types were accounted for by differences in
      lipid droplet density, not lipid droplet size. IMCL distribution showed an
      exponential increase in lipid content from the central region toward the
      sarcolemma, which was similar between groups and fiber types. In conclusion, IMCL
      contents can be substantially greater in trained endurance athletes compared with
      overweight and/or type 2 diabetes patients. Because structural characteristics
      and intramyocellular distribution of lipid aggregates seem to be similar between
      groups, we conclude that elevated IMCL deposits are unlikely to be directly
      responsible for inducing insulin resistance.

PMID- 15165999
TI  - Combined ingestion of protein and carbohydrate improves protein balance during
      ultra-endurance exercise.
AB  - The aims of this study were to compare different tracer methods to assess whole
      body protein turnover during 6 h of prolonged endurance exercise when
      carbohydrate was ingested throughout the exercise period and to investigate
      whether addition of protein can improve protein balance. Eight endurance-trained
      athletes were studied on two different occasions at rest (4 h), during 6 h of
      exercise at 50% of maximal O2 uptake (in sequential order: 2.5 h of cycling, 1 h
      of running, and 2.5 h of cycling), and during subsequent recovery (4 h). Subjects
      ingested carbohydrate (CHO trial; 0.7 g CHO.kg(-1.)h(-1)) or carbohydrate/protein
      beverages (CHO + PRO trial; 0.7 g CHO.kg(-1).h(-1) and 0.25 g PRO.kg(-1).h(-1))
      at 30-min intervals during the entire study. Whole body protein metabolism was
      determined by infusion of L-[1-13C]leucine, L-[2H5]phenylalanine, and [15N2]urea
      tracers with sampling of blood and expired breath. Leucine oxidation increased
      from rest to exercise [27 +/- 2.5 vs. 74 +/- 8.8 (CHO) and 85 +/- 9.5 vs. 200 +/-
      16.3 mg protein.kg(-1).h(-1) (CHO + PRO), P < 0.05], whereas phenylalanine
      oxidation and urea production did not increase with exercise. Whole body protein
      balance during exercise with carbohydrate ingestion was negative (-74 +/- 8.8, 
      17 +/- 1.1, and -72 +/- 5.7 mg protein.kg(-1).h(-1)) when L-[1-13C]leucine, L
      [2H5]phenylalanine, and [15N2]urea, respectively, were used as tracers. Addition
      of protein to the carbohydrate drinks resulted in a positive or less-negative
      protein balance (-32 +/- 16.3, 165 +/- 4.6, and 151 +/- 13.4 mg protein.kg(-1).h(
      1)) when L-[1-13C]leucine, L-[2H5]phenylalanine, and [15N2]urea, respectively,
      were used as tracers. We conclude that, even during 6 h of exhaustive exercise in
      trained athletes using carbohydrate supplements, net protein oxidation does not
      increase compared with the resting state and/or postexercise recovery. Combined
      ingestion of protein and carbohydrate improves net protein balance at rest as
      well as during exercise and postexercise recovery.

PMID- 15166000
TI  - V-type ATPase is involved in biogenesis of GLUT4 vesicles.
AB  - Proton pumps participate in several aspects of endocytic protein trafficking.
      However, their involvement specifically in the GLUT4 pathway has been a matter of
      great controversy. Here, we report that incubation of 3T3-L1 adipocytes with
      specific inhibitors of V-type ATPase, concanamycin A and bafilomycin A1, inhibits
      insulin-regulated glucose transport and results in accumulation of GLUT4 in
      heavy, rapidly sedimenting intracellular membranes. Correspondingly, the amount
      of small responsive GLUT4 vesicles in concanamycin A- and bafilomycin A1-treated
      cells is decreased. We conclude that these drugs block translocation of GLUT4 in
      adipose cells by inhibiting formation of small insulin-responsive vesicles on
      donor intracellular membranes. At the same time, proton pump inhibitors do not
      affect insulin-dependent translocation of preexisting vesicles or GLUT4 sorting
      in recycling endosomes. On the contrary, wortmannin acutely inhibits insulin
      dependent translocation of the preexisting vesicles but has no effect on vesicle
      formation.

PMID- 15166001
TI  - Insulin stimulates fatty acid transport by regulating expression of FAT/CD36 but
      not FABPpm.
AB  - Because insulin has been shown to stimulate long-chain fatty acid (LCFA)
      esterification in skeletal muscle and cardiac myocytes, we investigated whether
      insulin increased the rate of LCFA transport by altering the expression and the
      subcellular distribution of the fatty acid transporters FAT/CD36 and FABPpm. In
      cardiac myocytes, insulin very rapidly increased the expression of FAT/CD36
      protein in a time- and dose-dependent manner. During a 2-h period, insulin (10
      nM) increased cardiac myocyte FAT/CD36 protein by 25% after 60 min and attained a
      maximum after 90-120 min (+40-50%). There was a dose-dependent relationship
      between insulin (10(-12) to 10(-7) M) and FAT/CD36 expression. The half-maximal
      increase in FAT/CD36 protein occurred at 0.5 x 10(-9) M insulin, and the maximal
      increase occurred at 10(-9) to 10(-8) M insulin (+40-50%). There were similar
      insulin-induced increments in FAT/CD36 protein in cardiac myocytes (+43%) and in
      Langendorff-perfused hearts (+32%). In contrast to FAT/CD36, insulin did not
      alter the expression of FABPpm protein in either cardiac myocytes or the perfused
      heart. By use of specific inhibitors of insulin-signaling pathways, it was shown
      that insulin-induced expression of FAT/CD36 occurred via the PI 3-kinase/Akt
      insulin-signaling pathway. Subcellular fractionation of cardiac myocytes revealed
      that insulin not only increased the expression of FAT/CD36, but this hormone also
      targeted some of the FAT/CD36 to the plasma membrane while concomitantly lowering
      the intracellular depot of FAT/CD36. At the functional level, the insulin-induced
      increase in FAT/CD36 protein resulted in an increased rate of palmitate transport
      into giant vesicles (+34%), which paralleled the increase in plasmalemmal
      FAT/CD36 (+29%). The present studies have shown that insulin regulates protein
      expression of FAT/CD36, but not FABPpm, via the PI 3-kinase/Akt insulin-signaling
      pathway.

PMID- 15166002
TI  - Colon mucosa of patients both with spondyloarthritis and Crohn's disease is
      enriched with macrophages expressing the scavenger receptor CD163.
AB  - BACKGROUND: Crohn's disease is associated with an increased number of macrophages
      in ileal and colonic mucosa. Data on macrophages in gut mucosa of patients with
      spondyloarthritis (SpA) are scarce. OBJECTIVE: To investigate macrophages and
      other antigen presenting cells in gut mucosa from patients with SpA and Crohn's
      disease, given the relationship between both entities. METHODS: Biopsy specimens
      from patients with SpA, Crohn's disease, ulcerative colitis, and from controls
      were immunohistochemically stained with different markers for macrophages and
      dendritic cells. Slides were scored semiquantitatively on a four point scale.
      RESULTS: SpA and Crohn's disease were associated with large numbers of CD68+
      macrophages. Colon mucosa of both patients with SpA and Crohn's disease, but not
      ulcerative colitis, showed increased numbers of macrophages expressing the
      scavenger receptor CD163. CONCLUSIONS: Macrophages expressing the scavenger
      receptor CD163 are increased in colonic mucosa in SpA and in Crohn's disease,
      highlighting the relationship between these entities. The increased number of
      CD163+ macrophages in colon mucosa of patients with SpA suggests this is another
      argument for a role of macrophage scavenger receptors in this group of diseases.

PMID- 15166003
TI  - Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is
      modulated by infliximab treatment in rheumatoid arthritis.
AB  - OBJECTIVES: To analyse the effect of infliximab on IgM rheumatoid factor (RF) and
      anti-cyclic citrullinated peptide (CCP) antibodies, and determine whether
      baseline autoantibody titres (IgM RF and anti-CCP antibodies) are associated with
      changes in acute phase reactants. PATIENTS AND METHODS: 62 patients with
      refractory RA were treated with infliximab combined with methotrexate. At
      baseline and week 30, serum samples were tested for IgM RF by two agglutination
      assays, and for anti-CCP antibodies by an ELISA. Percentage change in C reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR) was calculated. RESULTS:
      At baseline and week 30 RF titres were reduced significantly during infliximab
      treatment (p<0.001 and p = 0.038, respectively), whereas anti-CCP antibodies were
      unchanged (p = 0.240). Baseline IgM RF titres, but not anti-CCP antibodies,
      correlated inversely with changes in CRP and ESR during treatment. Patients with
      a marked decrease in acute phase reactants had lower IgM RF titres than those
      with a smaller decrease in CRP and ESR; no significant differences were found for
      anti-CCP antibodies. CONCLUSION: The differential effect of infliximab treatment
      on IgM RF and anti-CCP antibodies, and the different predictive value on changes
      in acute phase reactants during infliximab treatment support the existing
      evidence that RF and anti-CCP antibodies are independent autoantibody systems in
      RA.

PMID- 15166004
TI  - Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility,
      and plasma CCK and GLP-1 in humans vary with their chain length.
AB  - The gastrointestinal effects of intraluminal fats may be critically dependent on
      the chain length of fatty acids released during lipolysis. We postulated that
      intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress
      appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the
      release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an
      identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19
      47 yr old) were studied on three occasions in a double-blind, randomized fashion.
      Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1
      concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2)
      C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at
      a buffet meal, immediately after completion of the infusion, was also quantified.
      C12, but not C10, suppressed appetite perceptions (P < 0.001) and energy intake
      (control: 4,604 +/- 464 kJ, C10: 4,109 +/- 588 kJ, and C12: 1,747 +/- 632 kJ; P <
      0.001, C12 vs. control/C10). C12, but not C10, also induced nausea (P < 0.001).
      C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed
      antral and duodenal PWs compared with control (P < 0.05 for all). C10 transiently
      stimulated isolated pyloric PWs (P = 0.001) and had no effect on antral PWs but
      markedly stimulated duodenal PWs (P = 0.004). C12 and C10 increased plasma CCK (P
      < 0.001), but the effect of C12 was substantially greater (P = 0.001); C12
      stimulated GLP-1 (P < 0.05), whereas C10 did not. In conclusion, there are major
      differences in the effects of intraduodenal C12 and C10, administered at 0.375
      kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone
      release in humans.

PMID- 15166006
TI  - Involvement of G protein-coupled receptor kinase 4 and 6 in rapid desensitization
      of dopamine D1 receptor in rat IEC-6 intestinal epithelial cells.
AB  - Dopamine-induced inhibition of Na(+)-K(+)-ATPase has been suggested to play a
      role in the regulation of Na(+) absorption at the intestinal level, and these
      effects were mediated by dopamine D(1)-like receptors. The aim of this work was
      to evaluate the effect of the activation of the D(1)-like receptors on the
      activity of the Na(+)/H(+) exchanger (NHE) in the rat intestinal epithelial cell
      line IEC-6. The presence of D(1) receptors was confirmed by immunoblotting. The
      dopamine D(1)-like receptor agonist SKF-38393 produced a concentration-dependent
      inhibition of NHE activity and stimulation of adenylyl cyclase (AC), this being
      antagonized by the D(1) selective antagonist SKF-83566. Effects of SKF-38393 on
      NHE and AC activities were maximal at 5 min of exposure to the agonist and
      rapidly diminished with no effect at 25 min. Exposure of cells for 25 min to
      dibutyryl-cAMP (0.5 mM) or to the AC activator forskolin (3 microM) effectively
      inhibited NHE activity. Pretreatment of cells with heparin (1 microM), a
      nonselective G protein-coupled receptor kinase (GRK) inhibitor, prevented the
      loss of effects on NHE activity after 25 min exposure to SKF-38393. The presence
      of GRK4, GRK6A, and GRK6B was confirmed by immunoblotting. Overnight treatment
      with the anti-GRK4-6 antibody complexed with Lipofectin was also effective in
      preventing loss of the effects of SKF-38393 on NHE and AC activities. It is
      concluded that dopamine D(1) receptors in IEC-6 rapidly desensitize to D(1)-like
      agonist stimulation and GRK4 and 6 appear to be involved in agonist-mediated
      responsiveness and desensitization.

PMID- 15166005
TI  - Vagal cooling and concomitant portal norepinephrine infusion do not reduce net
      hepatic glucose uptake in conscious dogs.
AB  - We examined the role of efferent neural signaling in regulation of net hepatic
      glucose uptake (NHGU) in two groups of conscious dogs with hollow perfusable
      coils around their vagus nerves, using tracer and arteriovenous difference
      techniques. Somatostatin, intraportal insulin and glucagon at fourfold basal and
      basal rates, and intraportal glucose at 3.8 mg.kg(-1).min(-1) were infused
      continuously. From 0 to 90 min [period 1 (P1)], the coils were perfused with a 37
      degrees C solution. During period 2 [P2; 90-150 min in group 1 (n = 3); 90-180
      min in group 2 (n = 6)], the coils were perfused with -15 degrees C solution to
      eliminate vagal signaling, and the coils were subsequently perfused with 37
      degrees C solution during period 3 (P3). In addition, group 2 received an
      intraportal infusion of norepinephrine at 16 ng.kg(-1).min(-1) during P2. The
      effectiveness of vagal suppression was demonstrated by the increase in heart rate
      during P2 (111 +/- 17, 167 +/- 16, and 105 +/- 13 beats/min in group 1 and 71 +/-
      6, 200 +/- 11, and 76 +/- 6 beats/min in group 2 during P1-P3, respectively) and
      by prolapse of the third eyelid during P2. Arterial plasma glucose, insulin, and
      glucagon concentrations; hepatic blood flow; and hepatic glucose load did not
      change significantly during P1-P3. NHGU during P1-P3 was 2.7 +/- 0.4, 4.1 +/-
      0.6, and 4.0 +/- 1.2 mg.kg(-1).min(-1) in group 1 and 5.0 +/- 0.9, 5.6 +/- 0.7,
      and 6.1 +/- 0.9 mg.kg(-1).min(-1) in group 2 (not significant among periods).
      Interruption of vagal signaling with or without intraportal infusion of
      norepinephrine to augment sympathetic tone did not suppress NHGU during portal
      glucose delivery, suggesting the portal signal stimulates NHGU independently of
      vagal efferent flow.

PMID- 15166007
TI  - Dietary phosphorus-responsive genes in the intestine, pyloric ceca, and kidney of
      rainbow trout.
AB  - Identification of phosphorus (P)-responsive genes is important in diagnosing the
      adequacy of dietary P intake well before clinical symptoms arise. The mRNA
      abundance of selected genes was determined in the intestine, pyloric ceca, and
      kidney of rainbow trout fed low-P (LP) or sufficient-P (SP) diet for 2, 5, and 20
      days. The LP-to-SP ratio (LP/SP) of mRNA abundance was used to evaluate the
      difference in gene expression between LP and SP fish, and to compare the response
      with bone and serum P, which are conventional indicators of P status. The LP/SP
      of intestinal, cecal, and renal type II sodium-phosphate cotransporter (NaPi-II)
      mRNA abundance changed from approximately 1-2 (day 2) to approximately 1.4-4 (day
      5) and to approximately 2-10 (day 20). The LP/SP of renal NaPi-II, vitamin D 24
      hydroxylase, and vitamin D receptor mRNA abundance correlated inversely with
      serum P on day 5 but not on day 2 and day 20. In another study, differentially
      expressed genes between LP and SP fish were examined by subtractive
      hybridization, confirmed by Northern blot, and evaluated by t-test and
      correlation with serum and bone P concentrations. About 30 genes were identified
      as dietary P responsive at day 20, including intestinal meprin and
      cysteinesulfinic acid decarboxylase, renal S100 calcium-binding protein and
      mitochondrial P(i) carrier, and cecal apolipoprotein E, somatomedin B-related
      protein, and NaPi-II. The LP/SP of mRNA abundance of renal mitochondrial P(i)
      carrier and intestinal cysteinesulfinic acid decarboxylase changed significantly
      by day 2, and intestinal meprin by day 5. Hence, these genes and NaPi-II are
      among the earliest steady-response genes capable of predicting P deficiency well
      before the onset of clinical deficiency.

PMID- 15166008
TI  - Human placental taurine transporter in uncomplicated and IUGR pregnancies:
      cellular localization, protein expression, and regulation.
AB  - Transplacental transfer is the fetus' primary source of taurine, an essential
      amino acid during fetal life. In intrauterine growth restriction (IUGR),
      placental transport capacity of taurine is reduced and fetal taurine levels are
      decreased. We characterized the protein expression of the taurine transporter
      (TAUT) in human placenta using immunocytochemistry and Western blotting, tested
      the hypothesis that placental protein expression of TAUT is reduced in IUGR, and
      investigated TAUT regulation by measuring the Na(+)-dependent taurine uptake in
      primary villous fragments after 1 h of incubation with different effectors. TAUT
      was primarily localized in the syncytiotrophoblast microvillous plasma membrane
      (MVM). TAUT was detected as a single 70-kDa band, and MVM TAUT expression was
      unaltered in IUGR. The PKC activator PMA and the nitric oxide (NO) donor 3
      morpholinosydnonimine decreased TAUT activity (P < 0.05, n = 7-15). However, none
      of the tested hormones, e.g., leptin and growth hormone, altered TAUT activity
      significantly. PKC activity measured in MVM from control and IUGR placentas was
      not different. In conclusion, syncytiotrophoblast TAUT is strongly polarized to
      the maternal-facing plasma membrane. MVM TAUT expression is unaltered in IUGR,
      suggesting that the reduced MVM taurine transport in IUGR is due to changes in
      transporter activity. NO release downregulates placental TAUT activity, and it
      has previously been shown that IUGR is associated with increased fetoplacental NO
      levels. NO may therefore play an important role in downregulating MVM TAUT
      activity in IUGR.

PMID- 15166009
TI  - Vascular protection: superoxide dismutase isoforms in the vessel wall.
AB  - Blood vessels express 3 isoforms of superoxide dismutase (SOD): cytosolic or
      copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD) localized in mitochondria, and
      an extracellular form of CuZn-SOD (EC-SOD). Because there are no selective
      pharmacological inhibitors of individual SOD isoforms, the functional importance
      of the different SODs has been difficult to define. Recent molecular approaches,
      primarily the use of genetically-altered mice and viral-mediated gene transfer,
      have allowed investigators to begin to define the role of specific SOD isoforms
      in vascular biology. This review will focus mainly on the role of individual SODs
      in relation to endothelium under normal conditions and in disease states. This
      area is important because reactive oxygen species and superoxide anion are
      thought to play major roles in changes in vascular structure and function in
      pathophysiology.

PMID- 15166010
TI  - Smad expression in human atherosclerotic lesions: evidence for impaired TGF
      beta/Smad signaling in smooth muscle cells of fibrofatty lesions.
AB  - OBJECTIVE: Transforming growth factor-beta (TGF-beta) has been implicated in the
      pathogenesis of human atherosclerosis but its actions during lesion progression
      are poorly understood. Smad2, Smad3, and Smad4 proteins are signaling molecules
      by which TGF-beta modulates gene transcription. Our objective was to define the
      actions of TGF-beta during lesion progression in humans by examining the
      expression of Smads in relation to TGF-beta-mediated responses. METHODS AND
      RESULTS: Immunohistochemistry and reverse-transcription polymerase chain reaction
      demonstrated Smad2, Smad3, and Smad4 expression in macrophages of fibrofatty
      lesions and their upregulation after differentiation of monocytes to macrophages.
      The major Smad splice variants expressed by the macrophages were those that are
      transcriptionally most active. Macrophages also expressed cyclin inhibitors whose
      expression is induced via Smad proteins. The cytoplasmic location of p21(Waf1)
      suggests it may protect macrophages from apoptosis. Smooth muscle cells (SMCs)
      within the fibrofatty lesions did not express the Smad proteins or the cyclin
      inhibitors. SMCs of fibrous plaques expressed all 3 Smad proteins. CONCLUSIONS:
      In human atherosclerotic lesions, the actions of TGF-beta appear restricted to
      SMCs in fibrous plaques and macrophages in fatty streaks/fibrofatty lesions. The
      lack of key TGF-beta signaling components in SMCs of fibrofatty lesions indicates
      impaired ability of these cells to initiate TGF-beta-mediated Smad-dependent
      transcriptional responses.

PMID- 15166011
TI  - Lipid inflammatory mediators in diabetic vascular disease.
AB  - Type 2 diabetes is associated with significantly accelerated rates of
      macrovascular complications such as atherosclerosis. Emerging evidence now
      indicates that atherosclerosis is an inflammatory disease and that certain
      inflammatory markers may be key predictors of diabetic atherosclerosis.
      Proinflammatory cytokines and cellular adhesion molecules expressed by vascular
      and blood cells during stimulation by growth factors and cytokines seem to play
      major roles in the pathophysiology of atherosclerosis and diabetic vascular
      complications. However, more recently, data suggest that inflammatory responses
      can also be elicited by smaller oxidized lipids that are components of
      atherogenic oxidized low-density lipoprotein or products of phospholipase
      activation and arachidonic acid metabolism. These include oxidized lipids of the
      lipoxygenase and cyclooxygenase pathways of arachidonic acid and linoleic acid
      metabolism. These lipids have potent growth, vasoactive, chemotactic, oxidative,
      and proinflammatory properties in vascular smooth muscle cells, endothelial
      cells, and monocytes. Cellular and animal models indicate that these enzymes are
      induced under diabetic conditions, have proatherogenic effects, and also mediate
      the actions of growth factors and cytokines. This review highlights the roles of
      the inflammatory cyclooxygenase and 12/15-lipoxygenase pathways in the
      pathogenesis of diabetic vascular disease. Evidence suggests that inflammatory
      responses in the vasculature can be elicited by small oxidized lipids that are
      components of oxidized low-density lipoprotein or products of the lipoxygenase
      and cyclooxygenase pathways of arachidonic and linoleic acid metabolism. This
      review evaluates these inflammatory and proatherogenic pathways in the
      pathogenesis of diabetic vascular disease.

PMID- 15166012
TI  - LRP1B attenuates the migration of smooth muscle cells by reducing membrane
      localization of urokinase and PDGF receptors.
AB  - OBJECTIVE: Studies on the involvement of low-density lipoprotein receptor
      relatives (LRs) in atherosclerosis have recently gained new focus because of the
      specific expression of certain of these receptors in the thickened intima. Here,
      we show that LRP1B, a member of LRs, modulates the migration of smooth muscle
      cells (SMCs) by increasing the degradation of membrane receptors, urokinase-type
      plasminogen activator receptor (uPAR), and platelet-derived growth factor
      receptor (PDGFR) beta. METHODS AND RESULTS: Immunohistochemistry showed that
      LRP1B expression in human coronary arteries is localized to the intimal SMCs near
      the plaque surface as well as to medial SMCs. LRP1B expression levels in cultured
      SMCs increase at the late phase of proliferation. Cell surface and
      internalization assays, in combination with coimmunoprecipitation experiments,
      showed that LRP1B binds and internalizes uPAR. Metabolic labeling analysis
      demonstrated that anti-LRP1B IgY decreased the catabolism of uPAR. In addition,
      the anti-LRP1B antibody raised PDGFRbeta protein and PDGFR-mediated
      phosphorylation levels of ERK1/2. Finally, the anti-LRP1B IgY enhanced the
      migration and invasion of SMCs in the presence of PDGF-BB. CONCLUSIONS: LRP1B
      modulates the catabolism of uPAR and PDGFR, affecting the migration of SMCs. This
      functional characterization of LRP1B opens novel avenues for elucidating the
      (patho)physiological significance of SMC migration in atheromatous plaques.

PMID- 15166013
TI  - Effects of conventional or lower doses of hormone replacement therapy in
      postmenopausal women.
AB  - OBJECTIVE: The effects of hormone replacement therapy (HRT) can affect many
      aspects relevant to cardiovascular disease, including vasomotor function,
      inflammation, and hemostasis. Recent studies have demonstrated that current doses
      of HRT exert a mixture of both protective and adverse effects. In the current
      study, we compared the effects of lower doses of HRT (L-HRT) and conventional
      doses of HRT (C-HRT) on a variety of relevant cardiovascular parameters. METHODS
      AND RESULTS: This randomized, double-blind, crossover study included 57 women who
      received micronized progesterone 100 mg with either conjugated equine estrogen
      0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. L-HRT showed comparable
      effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels,
      but not on low-density lipoprotein cholesterol levels. C-HRT and L-HRT
      significantly improved the percent flow-mediated dilator response to hyperemia
      from baseline values (both P<0.001) by a similar degree (P=0.719). C-HRT
      significantly increased high-sensitivity C-reactive protein (hsCRP) levels from
      baseline values (P<0.001); however, L-HRT did not significantly change hsCRP
      (P=0.874). C-HRT and L-HRT significantly decreased antithrombin III from baseline
      values (P<0.001 and P=0.042, respectively). C-HRT significantly increased
      prothrombin fragment 1+2 (F1+2) from baseline values (P<0.001); however, L-HRT
      did not significantly change F1+2 (P=0.558). Of interest, the effects of C-HRT
      and L-HRT on hsCRP, antithrombin III, and F1+2 were significantly different (all
      P<0.001). C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from
      baseline values (P=0.002 and P=0.038, respectively) to a similar degree
      (P=0.184). CONCLUSIONS: Compared with C-HRT, L-HRT has comparable effects on
      lipoproteins, flow-mediated dilation, and PAI-1 antigen levels. However, L-HRT
      did not increase hsCRP or F1+2 levels, and it decreased antithrombin III less
      than C-HRT.

PMID- 15166015
TI  - Correcting the loss of cell-cycle synchrony in clustering analysis of microarray
      data using weights.
AB  - MOTIVATION: Due to the existence of the loss of synchrony in cell-cycle data
      sets, standard clustering methods (e.g. k-means), which group open reading frames
      (ORFs) based on similar expression levels, are deficient unless the temporal
      pattern of the expression levels of the ORFs is taken into account. METHODS: We
      propose to improve the performance of the k-means method by assigning a
      decreasing weight on its variable level and evaluating the 'weighted k-means' on
      a yeast cell-cycle data set. Protein complexes from a public website are used as
      biological benchmarks. To compare the k-means clusters with the structures of the
      protein complexes, we measure the agreement between these two ways of clustering
      via the adjusted Rand index. RESULTS: Our results show the time-decreasing weight
      function--exp[-(1/2)(t(2)/C(2))]--which we assign to the variable level of k
      means, generally increases the agreement between protein complexes and k-means
      clusters when C is near the length of two cell cycles.

PMID- 15166016
TI  - DBRF-MEGN method: an algorithm for deducing minimum equivalent gene networks from
      large-scale gene expression profiles of gene deletion mutants.
AB  - MOTIVATION: Large-scale gene expression profiles measured in gene deletion
      mutants are invaluable sources for identifying gene regulatory networks. Signed
      directed graph (SDG) is the most common representation of gene networks in
      genetics and cell biology. However, no practical procedure that deduces SDGs
      consistent with such profiles has been developed. RESULTS: We developed the DBRF
      MEGN (difference-based regulation finding-minimum equivalent gene network) method
      in which an algorithm deduces the most parsimonious SDGs consistent with
      expression profiles of gene deletion mutants. Positive (or negative) directed
      edges representing positive (or negative) gene regulations are deduced by
      comparing the gene expression level between the wild-type and mutant. The most
      parsimonious SDGs are deduced using graph theoretical procedures. Compensation
      for excess removal of edges by restoring a minimum number of edges makes the
      method applicable to cyclic gene networks. Use of independent groups of edges
      greatly reduces the computational cost, thus making the method applicable to
      large-scale expression profiles. We confirmed the applicability of our method by
      applying it to the gene expression profiles of 265 Saccharomyces cerevisiae
      deletion mutants, and we confirmed our method's validity by comparing the
      pheromone response pathway, general amino acid control system, and copper and
      iron homeostasis system deduced by our method with those reported in the
      literature. Interpretation of the gene network deduced from the S. cerevisiae
      expression profiles by using our method led to the prediction of 132
      transcriptional targets and modulators of transcriptional activity of 18
      transcriptional regulators. AVAILABILITY: The software is available on request.

PMID- 15166014
TI  - Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related
      to mutations in PCSK9.
AB  - OBJECTIVE: We have reported further heterogeneity in familial autosomal-dominant
      hypercholesterolemia (FH) related to mutation in proprotein convertase
      subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated
      convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form
      of hypercholesterolemia. METHODS AND RESULTS: In vivo kinetics of apolipoprotein
      B100-containing lipoproteins using a 14-hour primed constant infusion of [2H3]
      leucine was conducted in 2 subjects carrying the mutation S127R in PCSK9,
      controls subjects, and FH subjects with known mutations on the low-density
      lipoprotein (LDL) receptor gene (LDL-R). Apo B100 production, catabolism, and
      transfer rates were estimated from very LDL (VLDL), intermediate-density
      lipoprotein (IDL), and LDL tracer enrichments by compartmental analysis. PCSK9
      mutation dramatically increased the production rate of apolipoprotein B100 (3
      fold) compared with controls or LDL-R mutated subjects, related to direct
      overproduction of VLDL (3-fold), IDL (3-fold), and LDL (5-fold). The 2 subjects
      also showed a decrease in VLDL and IDL conversion (10% to 30% of the controls).
      LDL fractional catabolic rate was slightly decreased (by 30%) compared with
      controls but still higher than LDL-R-mutated subjects. CONCLUSIONS: These results
      showed that the effect of the S127R mutation of PCSK9 on plasma cholesterol
      homeostasis is mainly related to an overproduction of apolipoprotein B100.

PMID- 15166017
TI  - Mining gene expression data based on template theory.
AB  - MOTIVATION: It is understood that clustering genes are useful for exploring
      scientific knowledge from DNA microarray gene expression data. The explored
      knowledge can be finally used for annotating biological function for novel genes.
      Representing the explored knowledge in an efficient manner is then closely
      related to the classification accuracy. However, this issue has not yet been paid
      the attention it deserves. RESULT: A novel method based on template theory in
      cognitive psychology and pattern recognition is developed in this study for
      representing knowledge extracted from cluster analysis effectively. The basic
      principle is to represent knowledge according to the relationship between genes
      and a found cluster structure. Based on this novel knowledge representation
      method, a pattern recognition algorithm (the decision tree algorithm C4.5) is
      then used to construct a classifier for annotating biological functions of novel
      genes. The experiments on five published datasets show that this method has
      improved the classification performance compared with the conventional method.
      The statistical tests indicate that this improvement is significant.
      AVAILABILITY: The software package can be obtained upon request from the author.

PMID- 15166018
TI  - Whole-genome prokaryotic phylogeny.
AB  - Current understanding of the phylogeny of prokaryotes is based on the comparison
      of the highly conserved small ssu-rRNA subunit and similar regions. Although such
      molecules have proved to be very useful phylogenetic markers, mutational
      saturation is a problem, due to their restricted lengths. Now, a growing number
      of complete prokaryotic genomes are available. This paper addresses the problem
      of determining a prokaryotic phylogeny utilizing the comparison of complete
      genomes. We introduce a new strategy, GBDP, 'genome blast distance phylogeny',
      and show that different variants of this approach robustly produce phylogenies
      that are biologically sound, when applied to 91 prokaryotic genomes. In this
      approach, first Blast is used to compare genomes, then a distance matrix is
      computed, and finally a tree- or network-reconstruction method such as UPGMA,
      Neighbor-Joining, BioNJ or Neighbor-Net is applied.

PMID- 15166019
TI  - CoPS: Comprehensive Peptide Signature database.
AB  - We present the development of a Comprehensive database of 12 076 invariant
      Peptide Signatures (CoPS) derived from 52 bacterial genomes with a minimum
      occurrence in at least seven organisms. These peptides were observed in
      functionally similar proteins and are distributed over nearly 1250 different
      functional proteins. The database provides function, structure and occurrence in
      biochemical pathways of the proteins containing these signature peptides. It
      houses additional information on the signature peptides, such as identical match
      in other motif/pattern (e.g. PROSITE, BLOCKS, PRINTS and Pfam) databases and the
      database of interacting proteins, human proteome and mutation effect on these
      signature peptides. There is a wide applicability of this database in the
      identification of critical functional residues in proteins. The database also
      facilitates the identification of folding nucleus/structural determinants in
      proteins and functional assignment to yet unknown proteins. We demonstrate
      functional assignment to 2605 hypothetical proteins in bacterial genomes and 112
      unknown proteins in human using this database. AVAILABILITY: The database can be
      freely accessed through the following URL:
      http://203.195.151.46/copsv2/index.html or http://203.90.127.70/copsv2/index.html

PMID- 15166021
TI  - Faster cyclic loess: normalizing RNA arrays via linear models.
AB  - MOTIVATION: Our goal was to develop a normalization technique that yields results
      similar to cyclic loess normalization and with speed comparable to quantile
      normalization. RESULTS: Fastlo yields normalized values similar to cyclic loess
      and quantile normalization and is fast; it is at least an order of magnitude
      faster than cyclic loess and approaches the speed of quantile normalization.
      Furthermore, fastlo is more versatile than both cyclic loess and quantile
      normalization because it is model-based. AVAILABILITY: The Splus/R function for
      fastlo normalization is available from the authors.

PMID- 15166020
TI  - ICBS: a database of interactions between protein chains mediated by beta-sheet
      formation.
AB  - MOTIVATION: Interchain beta-sheet (ICBS) interactions occur widely in protein
      quaternary structures, interactions between proteins and protein aggregation.
      These interactions play a central role in many biological processes and in
      diseases ranging from AIDS and cancer to anthrax and Alzheimer's. RESULTS: We
      have created a comprehensive database of ICBS interactions that is updated on a
      weekly basis and allows entries to be sorted and searched by relevance and other
      criteria through a simple Web interface. We derive a simple ICBS index to
      quantify the relative contributions of the beta-ladders in the overall interchain
      interaction and compute first- and second-order statistics regarding amino acid
      composition and pairing at different relative positions in the beta-strands.
      Analysis of the database reveals a 15.8% prevalence of significant ICBS
      interactions, the majority of which involve the formation of antiparallel beta
      sheets and many of which involve the formation of dimers and oligomers. The
      frequencies of amino acids in ICBS interfaces are similar to those in intrachain
      beta-sheet interfaces. A full range of non-covalent interactions between side
      chains complement the hydrogen-bonding interactions between the main chains.
      Polar amino acids pair preferentially with polar amino acids and non-polar amino
      acids pair preferentially with non-polar amino acids among antiparallel (i, j)
      pairs. We anticipate that the statistics and insights gained from the database
      will guide the development of agents that control interchain beta-sheet
      interactions and that the database will help identify new protein interactions
      and targets for these agents. AVAILABILITY: The database is available at:
      http://www.igb.uci.edu/servers/icbs/

PMID- 15166022
TI  - Command line tool for calculating theoretical MS spectra for given sequences.
AB  - Scientists usually want to verify the ion matching process of algorithms that
      look up peptide sequences in DNA or protein databases. The verification step is
      often done numerically or visually. Not all search algorithms present the
      appropriate theoretical spectrum information within their results. Thus, the
      theoretical spectrum for each result should be calculated from the sequence of
      the matched peptide. We present an operating-system-independent command line tool
      for this purpose that can be integrated easily into complex as well as existing
      environments, and can be used to present the theoretical spectrum to the user in
      either graphical or tabular format by third party products. AVAILABILITY: The
      code is available via the website http://www.protein-ms.de

PMID- 15166024
TI  - BacTregulators: a database of transcriptional regulators in bacteria and archaea.
AB  - MOTIVATION: The BacTregulators database is intended to collect and to integrate
      information on proteins belonging to defined families of transcriptional
      regulators in prokaryotes. RESULTS: The BacTregulators database currently
      contains data on two families of transcriptional regulators: AraC-XylS and TetR.
      The proteins included in the BacTregulators database have been identified by
      screening 123 genomes from archaea and bacteria and the SWISS-PROT and TrEMBL
      databases with profiles defining each family. As the result of an integration
      process, we have included 1326 different protein sequences from the AraC-XylS
      family and 1487 different protein sequences from the TetR family. The definition
      of an entry in BacTregulators is based on protein sequence, source organism,
      genome element and position in this genome element. The BacTregulators site
      allows the user to retrieve protein sequences, functional features and
      experimental evidence supporting the functions, references and the three
      dimensional structure of the regulator when available. BacTregulators supplies an
      innovative tool that allows the researcher to obtain an integrated report that
      shows the data corresponding to other entries which are related by sequence
      similarity to the query entry. BacTregulators detects and classifies the
      regulators belonging to AraC-XylS and TetR families present in prokaryotic
      genomes, and thus contributes to a more accurate annotation of regulators in
      genomes. The information collected on each protein in the family can be useful to
      characterize a new regulator or compile information on the biological properties
      of a known regulator. AVAILABILITY: The BacTregulators is available at
      www.bactregulators.org

PMID- 15166026
TI  - Data mining techniques to study the disulfide-bonding state in proteins: signal
      peptide is a strong descriptor.
AB  - In the eucaryotic cell, the formation of disulfide bonds takes place in general
      inside the endoplasmic reticulum which provides a unique folding environment. The
      DisulfideDB database gathers information about this biological process with
      structural, evolutionary and neighborhood information on cysteines in proteins.
      Mining this information with an association rule discovery program permits to
      extract some strong rules for the prediction of the disulfide-bonding state of
      cysteines.

PMID- 15166025
TI  - Qxpak: a versatile mixed model application for genetical genomics and QTL
      analyses.
AB  - MOTIVATION: Current methodology and software for quantitative trait loci (QTL)
      analyses do not use all available information and are inadequate to deal with the
      huge amount of QTL analyses to be needed in forecoming genetical genomics'
      studies. RESULTS: We show that a mixed model statistical framework provides a
      very flexible tool for QTL modeling in a variety of populations, be it a cross
      between inbred lines, a within population study, or experiments involving a
      mixture of populations or crosses. The software allows multitrait and multiQTL
      analyses, inclusion of infinitesimal genetic value and a batch multitrait option
      suitable for genetical genomics studies. It also allows massive association
      studies between single nucleotide polymorphisms and the trait(s) of interest.
      AVAILABILITY: A software (Qxpak), together with a manual and example files, is
      freely available for research purposes. So far, the compiled program is available
      for linux systems, the windows version will follow soon. See
      http://www.icrea.es/pag.asp?id=Miguel.Perez

PMID- 15166027
TI  - Regulatory motif finding by logic regression.
AB  - MOTIVATION: Multiple transcription factors coordinately control transcriptional
      regulation of genes in eukaryotes. Although many computational methods consider
      the identification of individual transcription factor binding sites (TFBSs), very
      few focus on the interactions between these sites. We consider finding TFBSs and
      their context specific interactions using microarray gene expression data. We
      devise a hybrid approach called LogicMotif composed of a TFBS identification
      method combined with the new regression methodology logic regression. LogicMotif
      has two steps: First, potential binding sites are identified from transcription
      control regions of genes of interest. Various available methods can be used in
      this step when the genes of interest can be divided into groups such as up-and
      downregulated. For this step, we also develop a simple univariate regression and
      extension method MFURE to extract candidate TFBSs from a large number of genes in
      the availability of microarray gene expression data. MFURE provides an
      alternative method for this step when partitioning of the genes into disjoint
      groups is not preferred. This first step aims to identify individual sites within
      gene groups of interest or sites that are correlated with the gene expression
      outcome. In the second step, logic regression is used to build a predictive model
      of outcome of interest (either gene expression or up- and down-regulation) using
      these potential sites. This 2-fold approach creates a rich diverse set of
      potential binding sites in the first step and builds regression or classification
      models in the second step using logic regression that is particularly good at
      identifying complex interactions. RESULTS: LogicMotif is applied to two publicly
      available datasets. A genome-wide gene expression data set of Saccharomyces
      cerevisiae is used for validation. The regression models obtained are
      interpretable and the biological implications are in agreement with the known
      resuts. This analysis suggests that LogicMotif provides biologically more
      reasonable regression models than previous analysis of this dataset with standard
      linear regression methods. Another dataset of S.cerevisiae illustrates the use of
      LogicMotif in classification questions by building a model that discriminates
      between up- and down-regulated genes in iron copper deficiency. LogicMotif
      identifies an inductive and two repressor motifs in this dataset. The inductive
      motif matches the binding site of the transcription factor Aft1p that has a key
      role in regulation of the uptake process. One of the novel repressor sites is
      highly present in transcription control regions of FeS genes. This site could
      represent a TFBS for an unknown transcription factor involved in repression of
      genes encoding FeS proteins in iron deficiency. We establish the robustness of
      the method to the type of outcome variable used by considering both continuous
      and binary outcome variables for this dataset. Our results indicate that logic
      regression used in combination with cluster/group operating binding site
      identification methods or with our proposed method MFURE is a powerful and
      flexible alternative to linear regression based motif finding methods.
      AVAILABILITY: Source code for logic regression is freely available as a package
      of the R programming language by Ruczinski et al. (2003) and can be downloaded at
      http://bear.fhcrc.org/~ingor/logic/download/download.html an R package for MFURE
      is available at http://www.stat.berkeley.edu/~sunduz/software.html

PMID- 15166028
TI  - Directed differentiation and mass cultivation of pure erythroid progenitors from
      mouse embryonic stem cells.
AB  - Differentiating embryonic stem (ES) cells are an increasingly important source of
      hematopoietic progenitors, useful for both basic research and clinical
      applications. Besides their characterization in colony assays, protocols exist
      for the cultivation of lymphoid, myeloid, and erythroid cells. With the possible
      exception of mast cells, however, long-term expansion of pure hematopoietic
      progenitors from ES cells has not been possible without immortalization caused by
      overexpression of exogenous genes. Here, we describe for the first time an
      efficient yet easy strategy to generate mass cultures of pure, immature erythroid
      progenitors from mouse ES cells (ES-EPs), using serum-free medium plus
      recombinant cytokines and hormones. ES-EPs represent long-lived, adult,
      definitive erythroid progenitors that resemble immature erythroid cells expanding
      in vivo during stress erythropoiesis. When exposed to terminal differentiation
      conditions, ES-EPs differentiated into mature, enucleated erythrocytes.
      Importantly, ES-EPs injected into mice did not exhibit tumorigenic potential but
      differentiated into normal erythrocytes. Both the virtually unlimited supply of
      cells and the defined culture conditions render our system a valuable tool for
      the analysis of factors influencing proliferation and maturation of erythroid
      progenitors. In addition, the system allows detailed characterization of
      processes during erythroid proliferation and differentiation using wild-type (wt)
      and genetically modified ES cells.

PMID- 15166029
TI  - Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed
      by FLT3 inhibition.
AB  - Pediatric acute myelogenous leukemia (AML) has a poor prognosis, and novel
      therapies are needed. The FLT3 tyrosine kinase represents a promising target in
      pediatric AML. FLT3 is constitutively activated either by an internal tandem
      duplication (ITD) or by a point mutation (PM) in 17% to 24% of pediatric AML
      cases. Autocrine stimulation of wild-type (WT) FLT3 by coexpressed FLT3 ligand
      (FL) occurs in many other cases. FLT3/ITD mutations confer a particularly poor
      prognosis in pediatric AML patients. Inhibitors of FLT3 are being tested in adult
      AML patients, with promising preliminary results. In this study, cytotoxicity and
      apoptosis assays were performed on 44 diagnostic pediatric AML blast samples (14
      FLT3/WT, 15 FLT3/ITD, 15 FLT3/PM) using CEP-701, a potent and selective FLT3
      inhibitor. Pronounced cytotoxicity and induction of apoptosis were observed in a
      higher percentage of FLT3/ITD samples (93%) than FLT3/PM (27%) or FLT3/WT (29%).
      The cytotoxicity was greatest in samples with a high FLT3/ITD mutant-to-wild-type
      allelic ratio. The addition of FL enhanced the survival and augmented the
      sensitivity to FLT3 inhibition for the CEP-701-responsive subset of FLT3/WT and
      FLT3/PM samples. Clinical testing of FLT3 inhibitors as molecularly targeted
      agents for the improvement of outcome of pediatric AML patients is warranted.

PMID- 15166030
TI  - Antitumor activity of rituximab plus thalidomide in patients with
      relapsed/refractory mantle cell lymphoma.
AB  - We evaluated a treatment strategy targeting both lymphoma cells (by rituximab)
      and the microenvironment (by thalidomide) in 16 patients with relapsed/refractory
      mantle cell lymphoma (MCL). Rituximab was administered at 375 mg/m(2) for 4
      weekly doses concomitantly with thalidomide (200 mg daily, with a dose increment
      to 400 mg on day 15), which was continued as maintenance therapy until
      progression/relapse. Thirteen patients (81%) experienced an objective response,
      with 5 complete responders (31%). Median progression-free survival (PFS) was 20.4
      months (95% confidence interval [CI], 17.3-23.6 months), and estimated 3-year
      survival was 75%. In patients achieving a complete response, PFS after rituximab
      plus thalidomide was longer than PFS after the preceding chemotherapy. Severe
      adverse events included 2 thromboembolic events and 1 grade IV neutropenia
      associated with thalidomide. Our results suggest that rituximab plus thalidomide
      has marked antitumor activity in relapsed/refractory MCL and a low toxicity
      profile, which warrants further evaluation in MCL.

PMID- 15166031
TI  - Bystander destruction of hematopoietic progenitor and stem cells in a mouse model
      of infusion-induced bone marrow failure.
AB  - Infusion of parental lymph node (LN) cells into sublethally irradiated hybrid F1
      recipients created a murine model for bone marrow (BM) failure. Affected animals
      developed fatal pancytopenia within 2 to 3 weeks, accompanied by BM oligoclonal T
      cell infiltration and severe marrow hypoplasia indicated by approximately 10-fold
      declines in total BM cellularity, 15-fold declines in BM Lin(-)Sca1(+)c-Kit(+)
      cells, 100-fold declines in spleen colony-forming units, and 100-fold declines in
      hematopoietic progenitor and stem cells as estimated by irradiation protection in
      vivo. LN cells of both H2(b/b) and H2(d/d) haplotypes were effectors. Serum
      interferon-gamma (IFN-gamma) concentration increased 2- to 3-fold. Marrow cells
      were severely apoptotic, with high proportions of Fas(+) and annexin V(+) cells.
      Cotransplantation of 5 x 10(5) BM cells from clinically affected donors and 10(6)
      BM cells from H2 identical healthy mice could not rescue lethally irradiated
      recipients. Recipients had significantly lower cellularity in peripheral blood
      and BM, and cell mixtures failed to produce a stromal feeder layer to support
      marrow cell growth in vitro. Pathogenic T cells from donors after BM failure
      appeared capable of destroying hematopoietic progenitor, stem, and stromal cells
      from fully compatible healthy donors as "innocent bystanders." This effect can be
      partially abrogated by anti-IFN-gamma antibody.

PMID- 15166032
TI  - Direct bacterial protein PAMP recognition by human NK cells involves TLRs and
      triggers alpha-defensin production.
AB  - Although human CD56(+)CD3(-) natural killer (NK) cells participate in immune
      responses against microorganisms, their capacity to directly recognize and be
      activated by pathogens remains unclear. These cells encode members of the Toll
      like receptor (TLR) family, involved in innate cell activation on recognition of
      pathogen-associated molecular patterns (PAMPs). We therefore evaluated whether
      the 2 bacterial protein PAMPs, the outer membrane protein A from Klebsiella
      pneumoniae (KpOmpA) and flagellin, which signal through TLR2 and TLR5,
      respectively, may directly stimulate human NK cells. These proteins induce
      interferon-gamma (IFN-gamma) production by NK cells and synergize with
      interleukin-2 (IL-2) and proinflammatory cytokines in PAMP-induced activation.
      Similar results were obtained using CD56(+)CD3(+) (NKR-expressing) T cells. NK
      cells from TLR2(-/-) mice fail to respond to KpOmpA, demonstrating TLR
      involvement in this effect. Defensins are antimicrobial peptides expressed mainly
      by epithelial cells and neutrophils that disrupt the bacterial membrane, leading
      to pathogen death. We show that NK cells and NKR-expressing T cells
      constitutively express alpha-defensins and that KpOmpA and flagellin rapidly
      induce their release. These data demonstrate for the first time that highly
      purified NK cells directly recognize and respond to pathogen components through
      TLRs and evidence defensins as a novel and direct cytotoxic pathway involved in
      NK cell-mediated protection against microorganisms.

PMID- 15166033
TI  - Imatinib targets other than bcr/abl and their clinical relevance in myeloid
      disorders.
AB  - Imatinib mesylate is a small molecule drug that in vitro inhibits the Abelson
      (Abl), Arg (abl-related gene), stem cell factor receptor (Kit), and platelet
      derived growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases. The
      drug has acquired therapeutic relevance because of similar inhibitory activity
      against certain activating mutations of these molecular targets. The archetypical
      disease in this regard is chronic myeloid leukemia, where abl is constitutively
      activated by fusion with the bcr gene (bcr/abl). Similarly, the drug has now been
      shown to display equally impressive therapeutic activity in eosinophilia
      associated chronic myeloproliferative disorders that are characterized by
      activating mutations of either the PDGFRB or the PDGFRA gene. The former usually
      results from translocations involving chromosome 5q31-33, and the latter usually
      results from an interstitial deletion involving chromosome 4q12 (FIP1L1-PDGFRA).
      In contrast, imatinib is ineffective, in vitro and in vivo, against the
      mastocytosis-associated c-kit D816V mutation. However, wild-type and other c-kit
      mutations might be vulnerable to the drug, as has been the case in
      gastrointestinal stomal cell tumors. Imatinib is considered investigational for
      the treatment of hematologic malignancies without a defined molecular drug
      target, such as polycythemia vera, myelofibrosis with myeloid metaplasia, and
      acute myeloid leukemia.

PMID- 15166035
TI  - Do antiangiogenic protein fragments have amyloid properties?
AB  - Tumor growth requires proteolytic activity. As a consequence, protein breakdown
      products are present in the circulation of patients with cancer. Within the past
      decade a large number of proteolytic fragments have been identified that inhibit
      angiogenesis and tumor growth. The mechanism of action of these inhibitors is
      still poorly understood. We recently found that the effects of the angiogenesis
      inhibitor endostatin on endothelial cells is critically dependent on the presence
      of cross-beta structure, a structure also present in amyloidogenic polypeptides
      in plaques of patients with amyloidosis, such as Alzheimer disease. We also
      showed that cross-beta structure containing endostatin is a ligand for tissue
      type plasminogen activator (tPA). We noted that many angiogenesis inhibitors
      stimulate tPA-mediated plasminogen activation. Because the presence of cross-beta
      structure is the common denominator in tPA-binding ligands, we hypothesize that
      these endogenous antiangiogenic proteolytic fragments share features with
      amyloidogenic polypeptides. We postulate that the cross-beta structural fold is
      present in these antiangiogenic polypeptide fragments and that this structure
      mediates the inhibitory effects. The hypothesis provides new insights in the
      potential mechanisms of these angiogenesis inhibitors and offers opportunities to
      improve their use.

PMID- 15166034
TI  - Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses
      in vivo after viral stimulation.
AB  - Like their human counterparts, mouse plasmacytoid dendritic cells (pDCs) play a
      central role in innate immunity against viral infections, but their capacity to
      prime T cells in vivo remains unknown. We show here that virus-activated pDCs
      differentiate into antigen-presenting cells able to induce effector/memory CD8(+)
      T-cell responses in vivo against both epitopic peptides and endogenous antigen,
      whereas pDCs activated by synthetic oligodeoxynucleotides containing unmethylated
      cytosine-guanine motifs (CpG) acquire only the ability to recall antigen
      experienced T-cell responses. We also show that immature pDCs are unable to
      induce effector or regulatory CD8(+) T-cell responses. Thus, murine pDCs take
      part in both innate and adaptive immune responses by directly priming naive
      CD8(+) T cells during viral infection.

PMID- 15166036
TI  - Constitutive activation of the MEK/ERK pathway mediates all effects of oncogenic
      H-ras expression in primary erythroid progenitors.
AB  - Oncogenic mutations in ras genes frequently occur in patients with myeloid
      disorders, and in these patients erythropoiesis is often affected. Previously, we
      showed that expression of oncogenic H-ras in purified mouse primary fetal liver
      erythroid progenitors blocks terminal erythroid differentiation and supports
      erythropoietin (Epo)-independent proliferation. As a first step in understanding
      the underlying molecular mechanisms we examined the signaling pathways downstream
      of Ras in primary erythroid cells. We found that 3 major pathways are abnormally
      activated by oncogenic H-ras: Raf/ERK (extracellular signal-regulated kinase),
      phosphatidyl inositol 3 (PI3)-kinase/Akt, and RalGEF/RalA. However, only
      constitutive activation of the MEK (MAPK [mitogen-activated protein kinase]/ERK
      kinase)/ERK pathway alone could recapitulate all of the effects of oncogenic H
      ras expression in blocking erythroid differentiation and inducing Epo-independent
      proliferation. Although expression of a constitutively active Akt kinase (ca.Akt)
      in erythroid progenitors does not significantly affect erythroid differentiation
      in the presence of Epo, coexpression of ca.Akt together with a constitutively
      active MEK causes prolonged Epo-independent proliferation of erythroid
      progenitors in addition to a block in differentiation. Moreover, the effects of
      oncogenic H-ras expression on primary erythroid cells are blocked by the addition
      of U0126, a specific inhibitor of MEK1 and MEK2, allowing normal terminal
      erythroid proliferation and differentiation. Our data suggest that the
      interruption of constitutive MEK/ERK signaling is a potential therapeutic
      strategy to correct impaired erythroid differentiation in patients with myeloid
      disorders.

PMID- 15166037
TI  - Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr
      independent HIV-1 replication in macrophages.
AB  - HIV-1 viral protein R (Vpr) shuttles between the nucleus and the cytoplasm and is
      believed to contribute to the process of nuclear translocation of the viral
      preintegration complex, thus facilitating HIV-1 replication in macrophages. In
      this report, we demonstrate that Hsp70, a heat-shock protein contributing to
      cellular stress responses, inhibits nuclear translocation of HIV-1 Vpr. In
      macrophages, Hsp70 is induced shortly after HIV-1 infection. Recombinant Hsp70 or
      a mild heat shock diminished replication of the wild-type HIV-1, suggesting that
      Hsp70 might function as an innate antiviral factor. Surprisingly, Hsp70
      stimulated nuclear import and replication in macrophages of the Vpr-deficient HIV
      1 construct. This finding suggests that Hsp70 and Vpr may function in a similar
      manner when expressed separately, but they neutralize each other's activity when
      present together. Consistent with this interpretation, Hsp70 coprecipitated with
      Vpr from HIV-1-infected cells.

PMID- 15166038
TI  - Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack.
AB  - Antiphospholipid antibodies represent a heterogeneous group of autoantibodies
      directed against anionic phospholipids (PLs) usually linked to protein cofactors.
      Their presence during the antiphospholipid syndrome is associated with risks of
      thrombosis and fetal losses. Among 5 randomly selected monoclonal
      antiphospholipid antibodies, all originating from a single patient suffering from
      this autoimmune disease, only 1 induced fetal losses when passively injected into
      pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its
      variable regions contained mainly 3 replacement mutations. To clarify the role of
      these mutations in the pathogenicity of the antibody, they were in vitro reverted
      to the germ line configuration. The resulting "germ line" antibody reacted with
      multiple self-antigens and only partially lost its reactivity against PLs, but it
      was no more dependent on annexin A5 and, more importantly, was no more
      pathogenic. This study illustrates that the in vivo antigen-driven maturation
      process of natural autoreactive B cells can be responsible for pathogenicity.

PMID- 15166040
TI  - Antibiotics, resistance, and clinical outcomes.

PMID- 15166039
TI  - Global warming.

PMID- 15166041
TI  - The free trade agreement between Australia and the United States.

PMID- 15166042
TI  - Cervical screening.

PMID- 15166044
TI  - Darfur teetering "on the verge of mass starvation".

PMID- 15166043
TI  - NICE guidance on newer drugs for epilepsy in adults.

PMID- 15166045
TI  - Italians are offered "do it yourself" paternity testing kits.

PMID- 15166049
TI  - First stem cell bank in the world is opened in UK.

PMID- 15166051
TI  - Nigeria postpones programme of polio immunisation.

PMID- 15166053
TI  - Israeli army accused of obstructing medical access to civilians.

PMID- 15166054
TI  - Top health officials adopt global plan to cut obesity.

PMID- 15166056
TI  - British Columbia can sue tobacco industry for healthcare costs.

PMID- 15166057
TI  - European and US groups draw up standards for CME.

PMID- 15166058
TI  - European guidelines on hypertension more flexible than those in United States.

PMID- 15166059
TI  - Lothian and Zambia join forces to tackle HIV/AIDS.

PMID- 15166061
TI  - Government promises measures to tackle obesity in children.

PMID- 15166062
TI  - Exodus of Polish doctors could threaten health system.

PMID- 15166063
TI  - Swapping Ilford for Baghdad.

PMID- 15166065
TI  - Teicoplanin induced drug hypersensitivity syndrome.

PMID- 15166064
TI  - Impact of use of hormone replacement therapy on false positive recall in the NHS
      breast screening programme: results from the Million Women Study.

PMID- 15166066
TI  - Psychological impact of human papillomavirus testing in women with borderline or
      mildly dyskaryotic cervical smear test results: cross sectional questionnaire
      study.
AB  - OBJECTIVE: To describe the psychological impact on women of being tested for
      human papillomavirus (HPV) when smear test results are borderline or mildly
      dyskaryotic. DESIGN: Cross sectional questionnaire study. SETTING: Two centres
      participating in an English pilot study of HPV testing in women with borderline
      or mildly dyskaryotic smear test results. PARTICIPANTS: Women receiving
      borderline or mildly dyskaryotic smear test results tested for HPV and found to
      be HPV positive (n = 536) or HPV negative (n = 331); and women not tested for HPV
      with borderline or mildly dyskaryotic smear results (n = 143) or normal smear
      results (n = 366). MAIN OUTCOME MEASURES: State anxiety, distress, and concern
      about test result, assessed within four weeks of receipt of results. RESULTS:
      Women with borderline or mildly dyskaryotic smear results who were HPV positive
      were more anxious, distressed, and concerned than the other three groups. Three
      variables independently predicted anxiety in HPV positive women: younger age
      (beta = -0.11, P = 0.03), higher perceived risk of cervical cancer (beta = 0.17,
      P < 0.001), and reporting that they did not understand the meaning of test
      results (beta = 0.17, P = 0.001). Testing HPV negative was not reassuring: among
      women with abnormal smear test results, those who were HPV negative were no less
      anxious than those who were not tested for HPV. CONCLUSIONS: Informing women more
      effectively about the meaning of borderline or mildly dyskaryotic smear test
      results and HPV status, in particular about the absolute risks of cervical cancer
      and the prevalence of HPV infection, may avoid some anxiety for those who are HPV
      positive while achieving some reassurance for those who test HPV negative.

PMID- 15166068
TI  - Legal issues of data anonymisation in research.

PMID- 15166067
TI  - Presence of bacteriuria caused by trimethoprim resistant bacteria in patients
      prescribed antibiotics: multilevel model with practice and individual patient
      data.
AB  - OBJECTIVE: To look for evidence of a relation between antibiotic resistance and
      prescribing by general practitioners by analysis of prescribing at both practice
      and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and
      1996. SETTING: 28 general practices in the Ninewells Hospital laboratory
      catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered
      with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME
      MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at
      practice and individual level simultaneously in a multilevel model. RESULTS:
      Practices showed considerable variation in both the prevalence of trimethoprim
      resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357
      prescriptions per 100 practice patients). Although variation in prescribing
      showed no association with resistance at the practice level after adjustment for
      other factors (P = 0.101), in the multilevel model resistance to trimethoprim was
      significantly associated with age, sex, and individual-level exposure to
      trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association
      with trimethoprim resistance was strongest for people recently exposed to
      trimethoprim, and there was no association for people with trimethoprim exposure
      more than six months before the date of the urine sample. DISCUSSION: Analysis of
      practice level data obscured important associations between antibiotic
      prescribing and resistance. The results support efforts to reduce unnecessary
      prescribing of antibiotics in the community and show the added value of
      individual patient data for research on the outcomes of prescribing.

PMID- 15166069
TI  - Forceps delivery in modern obstetric practice.

PMID- 15166070
TI  - Vaginal discharge--causes, diagnosis, and treatment.

PMID- 15166071
TI  - Munchausen syndrome by proxy and sudden infant death.

PMID- 15166072
TI  - Selecting, designing, and developing your questionnaire.

PMID- 15166073
TI  - The evidence base for shaken baby syndrome: response to editorial from 106
      doctors.

PMID- 15166074
TI  - Doctors' communication of trust, care, and respect: details of paper were
      incorrect.

PMID- 15166075
TI  - Doctors' communication of trust, care, and respect: paper was muddled.

PMID- 15166076
TI  - Doctors' communication of trust, care, and respect: it takes two to make
      therapeutic relationship work.

PMID- 15166077
TI  - Doctors' communication of trust, care, and respect: communication needs of all
      kinds of people should be explored.

PMID- 15166078
TI  - Doctors' communication of trust, care, and respect: communication entails more
      than being nice.

PMID- 15166079
TI  - Do patients with unexplained physical symptoms pressurise GPs for somatic
      treatment? Sorting the wheat from the chaff.

PMID- 15166081
TI  - Flaw in WHO Framework Convention on Tobacco Control: letter identified wrong
      problem with the framework convention.

PMID- 15166082
TI  - Flaw in WHO Framework Convention on Tobacco Control: question is scientific
      rather than cosmetic.

PMID- 15166083
TI  - Who should decide on caesarean sections?

PMID- 15166085
TI  - Does language lateralization depend on the hippocampus?

PMID- 15166087
TI  - DNA mismatch repair proteins promote apoptosis and suppress tumorigenesis in
      response to UVB irradiation: an in vivo study.
AB  - DNA mismatch repair (MMR) proteins are integral to the maintenance of genomic
      stability and suppression of tumorigenesis due to their role in repair of post
      replicative DNA errors. Recent data also support a role for MMR proteins in
      cellular responses to exogenous DNA damage that does not involve removal of DNA
      adducts. We have demonstrated previously that both Msh2- and Msh6-null primary
      mouse embryonic fibroblasts are significantly less sensitive to UVB (ultraviolet
      B)-induced cytotoxicity and apoptosis than wild-type control cells. In order to
      ascertain the physiological relevance of the data we have exposed MMR-deficient
      mice to acute and chronic UVB radiation. We found that MMR-deficiency was
      associated with reduced levels of apoptosis and increased residual UVB-induced
      DNA adducts in the epidermis 24-h following acute UVB exposure. Moreover, Msh2
      null mice developed UVB-induced skin tumors at a lower level of cumulative UVB
      exposure and with a greater severity of onset than wild-type mice. The Msh2-null
      skin tumors did not display microsatellite instability, suggesting that these
      tumors develop via a different tumorigenic pathway than tumors that develop
      spontaneously. Therefore, we propose that dysfunctional MMR promotes UVB-induced
      tumorigenesis through reduced apoptotic elimination of damaged epidermal cells.

PMID- 15166086
TI  - Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP
      1 suppresses growth of mammary carcinomas in transgenic mice.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix
      metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis.
      We developed transgenic mice to evaluate the relevance of circulating versus
      mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the
      control of the albumin (Alb) promoter for the production of large amounts of TIMP
      1 in the liver and release into the systemic circulation to achieve chronically
      elevated blood levels. The initial 7,12-dimethylbenz[a]anthracene (DMBA) mammary
      carcinogenesis study showed greatly decreased tumor incidence in heterozygous Alb
      TIMP-1 mice (25%), compared with their wild-type (wt) littermates (83.3%).
      Metastatic mammary carcinomas were induced in the Alb-TIMP-1 mice through
      breeding with mice expressing the polyomavirus Middle T antigen (MT) under the
      control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Both
      the mammary tumor burden and the incidence of lung metastases were lower in the
      Alb-TIMP-1/MMTV-MT mice than their MMTV-MT littermates. Analysis of the Alb-TIMP
      1/MMTV-MT tumors showed evidence of decreased proliferative activity and
      inhibition of apoptosis, whereas microvascular density was not affected.
      Transgenic expression of TIMP-1 in mammary epithelial cells was accomplished by
      using MMTV-LTR. In contrast to the Alb-TIMP-1 mice, there was insignificant
      difference in the growth of both DMBA- and MT-induced mammary tumors between
      heterozygous MMTV-TIMP-1 mice and their wt littermates. The MT-induced mammary
      tumors of the MMTV-TIMP-1 mice were separated into 'low' and 'high' TIMP-1
      expressing groups. The 'high' TIMP-1 expressing tumors exhibited significantly
      higher proliferative activity than the tumors of the MMTV-MT only mice, whereas
      the number of apoptotic cells and microvascular density were not different. The
      findings of this study show that circulating TIMP-1, but not mammary-derived TIMP
      1, has growth suppressive effects on DMBA and MT-induced mammary carcinomas.

PMID- 15166088
TI  - The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat
      pituitary tumor.
AB  - Edpm5 is one member of a group of quantitative trait loci that are responsible
      for the difference in susceptibility to estrogen-induced prolactinoma between the
      Fischer 344 (F344) and Brown Norway (BN) strains. Upon chronic estrogen treatment
      F344 rats develop large, hemorrhagic and invasive pituitary tumors, which exhibit
      both tumor angiogenesis and neoplasia. In contrast, BN rats do not develop a
      tumor despite an estrogen-induced increase in lactotroph density. To investigate
      the role of Edpm5 in the development of these tumors, we have generated a novel
      congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat
      chromosome bearing Edpm5 from BN into the F344 strain background. Phenotypic
      differences between F344 and F344.BN-Edpm5BN must be due to a gene(s) within the
      chromosomal interval encompassing Edpm5. Through use of these strains, we find
      that Edpm5 specifically regulates the switch to angiogenic phenotype, independent
      of neoplasia. The F344.BN-Edpm5BN rats developed tumors, which exhibited
      significant growth, 7-fold greater mass than the pituitary of untreated rats, and
      neoplasia indistinguishable from that of the F344 strain. However, the F344.BN
      Edpm5BN rat tumor had a non-angiogenic phenotype. After chronic estrogen
      treatment, there was no increase in microvessel count over untreated controls in
      F344.BN-Edpm5BN tumors, whereas F344 rat tumors showed a significant increase (P
      < 0.0005). The ultrastructural morphology of the pituitary blood vessels also did
      not show significant angiogenesis associated changes in F344.BN-Edpm5BN rat
      pituitary tumors. In contrast the parental strain F344 had pronounced angiogenic
      activity. The F344.BN-Edpm5BN strain also fails to express VEGF at the high
      levels seen in the F344 rat pituitary after estrogen treatment. Hence at least
      one gene that has a large impact, directly or indirectly, on the switch to
      angiogenic phenotype must reside within the chromosomal interval that is the
      Edpm5 quantitative trait locus.

PMID- 15166089
TI  - Increased susceptibility to urethane-induced lung tumors in mice with decreased
      expression of connexin43.
AB  - Gap junction intercellular communication capacity and connexin expression are
      reportedly decreased in human lung cancer. The mechanisms by which connexins, the
      gap junction proteins, act as tumor suppressors are unclear. In order to
      understand the involvement of connexins in tumorigenesis, we analyzed the effect
      of the heterologous deletion of Gja1 [the connexin43 (Cx43) gene] on the
      development of lung adenomas in mice. Heterozygous (Cx43(+/-)) and wild-type mice
      (Cx43(+/+)) were treated or not with single doses of urethane at 15 and 17 days
      after birth. Twenty-five weeks later, both the number and size of nodules were
      increased in Cx43(+/-) mice as compared with Cx43(+/+) mice. Moreover, the
      lesions were histologically more aggressive in the heterozygous mice. However, no
      increase in spontaneous lesions was observed in the lungs of untreated Cx43(+/-)
      mice. Heterozygous mice effectively presented lower expression of Cx43 genes and
      decreased amounts of Cx43. In conclusion, our results indicate that deletion of
      one allele of the Cx43 gene clearly favors the carcinogenic effect of urethane
      administration and results in a higher susceptibility to lung adenoma formation
      in mice.

PMID- 15166090
TI  - Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic
      mouse.
AB  - Thioredoxin-1 is a low molecular weight redox protein that protects cells against
      oxidant damage. Thioredoxin-1 levels are increased in the epidermal layer of sun
      damaged human skin. Thioredoxin-1 levels are also increased in several human
      primary tumors where its expression is associated with increased tumor cell
      proliferation, decreased apoptosis and aggressive tumor growth. We have
      investigated whether increased thioredoxin-1 levels in skin can lead to increased
      tumor formation using transgenic mice with mouse thioredoxin-1 expressed in
      keratinocytes under the control of the keratinocyte-14 (K14) promoter.
      Thioredoxin-1 protein expression was increased 2-fold in the keratinocyte layer
      of the transgenic mice. The skin was macroscopically and histologically normal
      but in the two-stage model of carcinogenesis using topical dimethylbenzanthracene
      (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a
      promoting agent, there was a 6-fold increase in the number of papillomas per
      mouse and a 3-fold increase in papilloma size in the K14 thioredoxin-1 transgenic
      mice compared with non-transgenic littermates. Thus, increased thioredoxin-1 in
      keratinocytes acts as an enhancer of carcinogenesis in the DMBA/TPA two-stage
      model of skin carcinogenesis in mice.

PMID- 15166091
TI  - The adaptive imbalance to genotoxic stress: genome guardians rear their ugly
      heads.
AB  - An adaptive response of the genome-protection machinery occurs in cells exposed
      to genotoxic stress. This machinery includes the p53 and retinoblastoma protein
      pathways, which are not mutually exclusive from other adapting machinery
      including DNA repair, cell cycle checkpoints, apoptosis and endogenous
      metabolizing and antioxidant enzymes. The adaptive changes occur in chronic
      inflammation and in cigarette smokers associated with a high cancer risk, and are
      an attempt to keep cells healthy. However, there is increasing evidence that this
      response may have deleterious effects. Here, key pathways that adaptively respond
      to genotoxic stress are reviewed and mechanisms by which this response may have
      pro-carcinogenic implications are discussed.

PMID- 15166092
TI  - Contribution of fluid shear response in leukocytes to hemodynamic resistance in
      the spontaneously hypertensive rat.
AB  - The mechanisms for elevation of peripheral vascular resistance in spontaneously
      hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are
      unresolved. An increase in hemodynamic resistance caused by circulating blood may
      be a factor. Physiological fluid shear stress induces a variety of responses in
      circulating leukocytes, including pseudopod retraction. Due to high rigidity,
      leukocytes with pseudopods have greater difficulty to pass through capillaries.
      Because SHR have more circulating leukocytes with pseudopods, we hypothesize that
      inhibition of the leukocyte shear response by glucocorticoids in SHR impairs
      normal leukocyte passage through capillaries and causes enhanced resistance in
      capillary channels. Fluid shear leads to retraction of pseudopods in normal
      leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone
      treated Wistar rats. The high incidence of circulating leukocytes with pseudopods
      results in slower cell passage through capillaries under normal blood flow and
      during reduced flow enhanced capillary plugging both in vivo and in vitro. SHR
      blood requires higher pressure (90.0+/-8.2 mm Hg) than Wistar Kyoto rat (WKY,
      69.6+/-6.5 mm Hg; P<0.0001) or adrenalectomized SHR (73.5+/-2.1 mm Hg; P=0.0009)
      at the same flow rate in the resting hemodynamically isolated skeletal muscle
      microcirculation. Intravenous injection of blood from SHR, but not WKY, causes
      blood pressure increase in normal rats, which depends on pseudopod formation. We
      conclude that in addition to enhanced vascular tone, pseudopod formation with
      lack of normal fluid shear response may serve as mechanisms for an elevated
      hemodynamic resistance in SHR.

PMID- 15166093
TI  - Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs.
AB  - Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial
      infarction (MI) both contribute to arrhythmogenesis and sudden death. However,
      the mechanisms responsible for nerve sprouting after MI are unclear. The
      expression of nerve growth factor (NGF), growth associated protein 43 (GAP43),
      and other nerve markers were studied at the infarcted site, the noninfarcted left
      ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time
      points (30 minutes to 1 month) after MI. Transcardiac (difference between
      coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the
      immediate elevation of the transcardiac NGF concentration within 3.5 hours after
      MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was
      earlier and more pronounced at the infarcted site than the noninfarcted LVFW.
      However, cardiac nerve sprouting and sympathetic hyperinnervation were more
      pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week
      after MI. The NGF and GAP43 protein levels significantly increased in the LSG
      from 3 days (P<0.01 for all) after MI, without a concomitant increase in mRNA.
      There was persistent elevation of NGF levels in aorta and coronary sinus within 1
      month after MI. We conclude MI results in immediate local NGF release, followed
      by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43
      are transported retrogradely to LSG, which triggers nerve sprouting at the
      noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43
      expression at the infarcted site underlies the mechanisms of cardiac nerve
      sprouting after MI.

PMID- 15166094
TI  - Cardioprotection during the final stage of the late phase of ischemic
      preconditioning is mediated by neuronal NO synthase in concert with
      cyclooxygenase-2.
AB  - The infarct-sparing effect of the late phase of ischemic preconditioning (late
      PC) lasts for 72 hours. Upregulation of both cyclooxygenase-2 (COX-2) and
      inducible NO synthase (iNOS) has been shown to be essential to the protection in
      the initial stage of late PC (24 hours after PC); however, the mechanisms
      underlying the protection in the final stage of late PC (48 to 72 hours after PC)
      are unknown. Conscious rabbits were preconditioned with six cycles of 4-minute
      coronary occlusion/4-minute reperfusion. At 72 hours after PC, powerful
      protection against infarction was associated with increased myocardial levels of
      COX-2 mRNA, protein, and cardioprotective prostaglandins (PGI2 and PGE2). The COX
      2-selective inhibitor NS-398 completely blocked the protection. Surprisingly,
      iNOS expression was not increased at 72 hours; instead, upregulation of neuronal
      NO synthase (nNOS) was evident at both the mRNA (+266+/-20%, P<0.005) and the
      protein levels (+195+/-66%, P<0.005), which was accompanied by an increase in
      myocardial nitrite/nitrate (+20+/-4%, P<0.05). The nNOS-selective inhibitors N
      propyl-l-arginine or S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea completely
      blocked the protection of late PC at 72 hours, whereas the iNOS-selective
      inhibitor S-methylisothiourea had no effect. In line with these findings, the
      disappearance of protection at 120 hours after PC was associated with the return
      of nNOS mRNA, protein, and activity to control levels. Although expression of COX
      2 protein was still elevated at 120 hours, only a marginal increase in PGI2 and
      PGE2 levels was detected. In contrast to 72 hour after PC, nNOS was not
      upregulated at 24 hour after PC. We conclude that (1) the cardioprotection
      observed in the final stage of late PC (72 hour) is mediated by nNOS, not by
      iNOS, in concert with COX-2, and (2) nNOS-derived NO is required to drive COX-2
      activity. These data identify, for the first time, a cardioprotective role of
      nNOS and demonstrate, surprisingly, that the mechanism of late PC differs at 72
      hours (nNOS) versus 24 hours (iNOS).

PMID- 15166095
TI  - Activated protein C induces endothelial cell proliferation by mitogen-activated
      protein kinase activation in vitro and angiogenesis in vivo.
AB  - Activated protein C (APC), a natural anticoagulant, has recently been
      demonstrated to activate the mitogen-activated protein kinase (MAPK) pathway in
      endothelial cells in vitro. Because the MAPK pathway is implicated in endothelial
      cell proliferation, it is possible that APC induces endothelial cell
      proliferation, thereby causing angiogenesis. We examined this possibility in the
      present study. APC activated the MAPK pathway, increased DNA synthesis, and
      induced proliferation in cultured human umbilical vein endothelial cells
      dependent on its serine protease activity. Antibody against the endothelial
      protein C receptor (EPCR) inhibited these events. Early activation of the MAPK
      pathway was inhibited by an antibody against protease-activated receptor-1,
      whereas neither late and complete activation of the MAPK pathway nor endothelial
      cell proliferation were inhibited by this antibody. APC activated endothelial
      nitric oxide synthase (eNOS) via phosphatidylinositol 3-kinase-dependent
      phosphorylation, followed by activation of protein kinase G, suggesting that APC
      bound to EPCR might activate the endothelial MAPK pathway by a mechanism similar
      to that of VEGF. APC induced morphogenetic changes resembling tube-like
      structures of endothelial cells, whereas DIP-APC did not. When applied topically
      to the mouse cornea, APC clearly induced angiogenesis in wild-type mice, but not
      in eNOS knockout mice. These in vitro events induced by APC might at least partly
      explain the angiogenic activity in vivo. This angiogenic activity of APC might
      contribute to maintain proper microcirculation in addition to its antithrombotic
      activity.

PMID- 15166097
TI  - Human brain regions involved in recognizing environmental sounds.
AB  - To identify the brain regions preferentially involved in environmental sound
      recognition (comprising portions of a putative auditory 'what' pathway), we
      collected functional imaging data while listeners attended to a wide range of
      sounds, including those produced by tools, animals, liquids and dropped objects.
      These recognizable sounds, in contrast to unrecognizable, temporally reversed
      control sounds, evoked activity in a distributed network of brain regions
      previously associated with semantic processing, located predominantly in the left
      hemisphere, but also included strong bilateral activity in posterior portions of
      the middle temporal gyri (pMTG). Comparisons with earlier studies suggest that
      these bilateral pMTG foci partially overlap cortex implicated in high-level
      visual processing of complex biological motion and recognition of tools and other
      artifacts. We propose that the pMTG foci process multimodal (or supramodal)
      information about objects and object-associated motion, and that this may
      represent 'action' knowledge that can be recruited for purposes of recognition of
      familiar environmental sound-sources. These data also provide a functional and
      anatomical explanation for the symptoms of pure auditory agnosia for
      environmental sounds reported in human lesion studies.

PMID- 15166096
TI  - Embryonic heart failure in NFATc1-/- mice: novel mechanistic insights from in
      utero ultrasound biomicroscopy.
AB  - Gene targeting in the mouse has become a standard approach, yielding important
      new insights into the genetic factors underlying cardiovascular development and
      disease. However, we still have very limited understanding of how mutations
      affect developing cardiovascular function, and few studies have been performed to
      measure altered physiological parameters in mouse mutant embryos. Indeed,
      although in utero lethality due to embryonic heart failure is one of the most
      common results of gene targeting experiments in the mouse, the underlying
      physiological mechanisms responsible for embryonic demise remain elusive. Using
      in utero ultrasound biomicroscopy (UBM), we studied embryonic day (E) 10.5 to
      14.5 NFATc1-/- embryos and control littermates. NFATc1-/- mice, which lack
      outflow valves, die at mid-late gestation from presumed defects in forward blood
      flow with resultant heart failure. UBM showed increasing abnormal regurgitant
      flow in the aorta and extending into the embryonal-placental circulation, which
      was evident after E12.5 when outflow valves normally first develop. Reduced
      NFATc1-/- net volume flow and diastolic dysfunction contributed to heart failure,
      but contractile function remained unexpectedly normal. Among 107 NFATc1-/-
      embryos imaged, only 2 were observed to be in acute decline with progressive
      bradyarrhythmia, indicating that heart failure occurs rapidly in individual
      NFATc1-/- embryos. This study is among the first linking a specific physiological
      phenotype with a defined genotype, and demonstrates that NFATc1-/- embryonic
      heart failure is a complex phenomenon not simply attributable to contractile
      dysfunction.

PMID- 15166098
TI  - Ethanol induces heterotopias in organotypic cultures of rat cerebral cortex.
AB  - Abnormalities in the migration of cortical neurons to ectopic sites can be caused
      by prenatal exposure to ethanol. In extreme cases, cells migrate past the pial
      surface and form suprapial heterotopias or 'warts'. We used organotypic slice
      cultures from 17-day-old rat fetuses to examine structural and molecular changes
      that accompany wart formation. Cultures were exposed to ethanol (0, 200, 400 or
      800 mg/dl) and maintained for 2-32 h. Fixed slices were sectioned and
      immunolabeled with antibodies directed against calretinin, reelin, nestin, GFAP,
      doublecortin, MAP-2 and NeuN. Ethanol promoted the widespread infiltration of the
      marginal zone (MZ) with neurons and the focal formation of warts. The appearance
      of warts is time- and concentration-dependent. Heterotopias comprised migrating
      neurons and were not detected in control slices. Warts were associated with
      breaches in the array of Cajal-Retzius cells and with translocation of reelin
      immunoexpression from the MZ to the outer limit of the wart. Ethanol also altered
      the morphology of the radial glia. Thus, damage to the integrity of superficial
      cortex allows neurons to infiltrate the MZ, and if the pial-subpial glial barrier
      is also compromised these ectopic neurons can move beyond the normal cerebral
      limit to form a wart.

PMID- 15166099
TI  - Remembering our past: functional neuroanatomy of recollection of recent and very
      remote personal events.
AB  - Functional magnetic resonance imaging was used to study brain regions implicated
      in retrieval of memories that are decades old. To probe autobiographical memory,
      family photographs were selected by confederates without the participant's
      involvement, thereby eliminating many of the variables that potentially
      confounded previous neuroimaging studies. We found that context-rich memories
      were associated with activity in lingual and precuneus gyri independently of
      their age. By contrast, retrosplenial cortex was more active for recent events
      regardless of memory vividness. Hippocampal activation was related to the
      richness of re-experiencing (vividness) rather than the age of the memory per se.
      Remote memories were associated with distributed activation along the
      rostrocaudal axis of the hippocampus whereas activation associated with recent
      memories was clustered in the anterior portion. This may explain why
      circumscribed lesions to the hippocampus disproportionately affect recent
      memories. These findings are incompatible with theories of long-term memory
      consolidation, and are more easily accommodated by multiple-trace theory, which
      posits that detailed memories are always dependent on the hippocampus.

PMID- 15166100
TI  - Fine modulation in network activation during motor execution and motor imagery.
AB  - Motor imagery, the 'mental rehearsal of motor acts without overt movements',
      involves either a visual representation (visual imagery, VI) or mental simulation
      of movement, associated with a kinesthetic feeling (kinetic imagery, KI).
      Previous brain imaging work suggests that patterns of brain activation differ
      when comparing execution (E) with either type of imagery but the functional
      connectivity of the participating networks has not been studied. Using functional
      magnetic resonance imaging (fMRI) and structural equation modeling, this study
      elucidates the inter-relationships among the relevant areas for each of the three
      motor behaviors. Our results suggest that networks underlying these behaviors are
      not identical, despite the extensive overlap between E and KI. Inputs to M1,
      which are facilitatory during E, have the opposite effect during KI, suggesting a
      physiological mechanism whereby the system prevents overt movements. Finally,
      this study highlights the role of the connection of superior parietal lobule to
      the supplementary motor area in both types of motor imagery.

PMID- 15166101
TI  - Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of
      layer V pyramidal neurons in vivo and in vitro.
AB  - There are two main types of layer V pyramidal neurons in rat cortex. Type I
      neurons have tufted apical dendrites extending into layer I, produce bursts of
      action potentials and project to subcortical targets (spinal cord, superior
      colliculus and pontine nuclei). Type II neurons have apical dendrites, which
      arborize in layers II-IV, do not produce bursts of action potentials and project
      to ipsilateral and contralateral cortex. The specific expression of different
      genes and proteins in these two distinct layer V neurons is unknown. To
      distinguish between distinct subpopulations, fluorescent microspheres were
      injected into subcortical targets (labeling type I neurons) or primary
      somatosensory cortex (labeling type II neurons) of adult rats. After transport,
      cortical sections were processed for immunohistochemistry using various
      antibodies. This study demonstrated that antigens recognized by SMI-32, N200 and
      FNP-7 antibodies were only expressed in subcortical (type I)--but not in
      contralateral (type II)--projecting neurons. NR1, NR2a/b, PLCbeta1, BDNF, NGF and
      TrkB antigens were highly expressed in all neuronal subpopulations examined.
      Organotypic culture experiments demonstrated that the development of
      neurofilament expression and laminar specificity does not depend on the presence
      of the subcortical targets. This study suggests specific markers for the
      subcortical projecting layer V neuron subpopulations.

PMID- 15166102
TI  - Modulation of LIP activity by predictive auditory and visual cues.
AB  - The lateral intraparietal area (area LIP) contains a multimodal representation of
      extra-personal space. To further examine this representation, we trained rhesus
      monkeys on the predictive-cueing task. During this task, monkeys shifted their
      gaze to a visual target whose location was predicted by the location of an
      auditory or visual cue. We found that, when the sensory cue was at the same
      location as the visual target, the monkeys' mean saccadic latency was faster than
      when the sensory cue and the visual target were at different locations. This
      difference in mean saccadic latency was the same for both auditory cues and
      visual cues. Despite the fact that the monkeys used auditory and visual cues in a
      similar fashion, LIP neurons responded more to visual cues than to auditory cues.
      This modality-dependent activity was also seen during auditory and visual memory
      guided saccades but to a significantly greater extent than during the predictive
      cueing task. Additionally, we found that the firing rate of LIP neurons was
      inversely correlated with saccadic latency. This study indicates further that
      modality-dependent differences in LIP activity do not simply reflect differences
      in sensory processing but also reflect the cognitive and behavioral requirements
      of a task.

PMID- 15166103
TI  - 3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections
      to the human striatum.
AB  - Studies in non-human primates have shown that medial premotor projections to the
      striatum are characterized as a set of distinct circuits conveying different type
      of information. This study assesses the anatomical projections from the
      supplementary motor area (SMA), pre-SMA and motor cortex (MC) to the human
      striatum using diffusion tensor imaging (DTI) axonal tracking. Eight right-handed
      volunteers were studied at 1.5 T using DTI axonal tracking. A connectivity matrix
      was computed, which tested for connections between cortical areas (MC, SMA and
      pre-SMA) and subcortical areas (posterior, middle and anterior putamen and the
      head of the caudate nucleus) in each hemisphere. Pre-SMA projections to the
      striatum were located rostral to SMA projections to the striatum. The SMA and the
      MC were similarly connected to the posterior and middle putamen and not to the
      anterior striatum. These data show that the MC and SMA have connections with
      similar parts of the sensorimotor compartment of the human striatum, whereas the
      pre-SMA sends connections to more rostral parts of the striatum, including the
      associative compartment.

PMID- 15166104
TI  - Population vector analysis of primate prefrontal activity during spatial working
      memory.
AB  - Population vectors were used to examine information represented by a population
      of prefrontal activity and its temporal change during spatial working memory
      processes while monkeys performed ODR and R-ODR tasks. In the ODR task, monkeys
      made a saccade to the cue location after the delay, whereas in the R-ODR task,
      they made a saccade 90 degrees clockwise from the cue location. We first
      constructed population vectors using cue- and response-period activity. The
      directions of population vectors were similar to the cue directions and the
      saccade target directions, respectively, indicating that population vectors
      correctly represented information regarding directions of visual cues and saccade
      targets. We then calculated population vectors during a 250 ms time-window from
      the cue presentation to the end of the response period. In the ODR task, all
      population vectors were directed toward the cue direction. However, in the R-ODR
      task, the population vector gradually rotated during the delay period from the
      cue direction to the saccade direction. These results indicate that spatial
      information represented by a population of prefrontal activity can be shown as
      the direction of the population vector and that its temporal change during
      spatial working memory tasks can be depicted as the temporal change of the
      vector's direction.

PMID- 15166105
TI  - Control of object-based attention in human cortex.
AB  - Visual attention is a mechanism by which observers select relevant or important
      information from the current visual array. Previous investigations have focused
      primarily on the ability to select a region of space for further visual analysis.
      These studies have revealed a distributed frontoparietal circuit that is
      responsible for the control of spatial attention. However, vision must ultimately
      represent objects and in real scenes objects often overlap spatially; thus
      attention must be capable of selecting objects and their properties nonspatially.
      Little is known about the neural basis of object-based attentional control. In
      two experiments, human observers shifted attention between spatially superimposed
      faces and houses. Event-related functional magnetic resonance imaging (fMRI)
      revealed attentional modulation of activity in face- and house-selective cortical
      regions. Posterior parietal and frontal regions were transiently active when
      attention was shifted between spatially superimposed perceptual objects. The
      timecourse of activity provides insight into the functional role that these brain
      regions play in attentional control processes.

PMID- 15166106
TI  - In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5
      HT3 receptors.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) controls pyramidal cell activity in
      prefrontal cortex (PFC) through various receptors, in particular, 5-HT1A and 5
      HT2A receptors. Here we report that the physiological stimulation of the raphe
      nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate
      areas of the rat PFC in vivo. These excitations had a latency of 36 +/- 4 ms and
      a duration of 69 +/- 9 ms and were blocked by the i.v. administration of the 5
      HT3 receptor antagonists ondansetron and tropisetron. The latency and duration
      were shorter than those elicited through 5-HT2A receptors in pyramidal neurons of
      the same areas. Double in situ hybridization histochemistry showed the presence
      of GABAergic neurons expressing 5-HT3 receptor mRNA in PFC. These cells were more
      abundant in the cingulate, prelimbic and infralimbic areas, particularly in
      superficial layers. The percentages of GAD mRNA-positive neurons expressing 5-HT3
      receptor mRNA in prelimbic cortex were 40, 18, 6 and 8% in layers I, II-III, V
      and VI, respectively, a distribution complementary to that of cells expressing 5
      HT2A receptors. Overall, these results support an important role of 5-HT in the
      control of the excitability of apical dendrites of pyramidal neurons in the
      medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.

PMID- 15166107
TI  - Toward resolving the challenges of sepsis diagnosis.
AB  - Sepsis in the United States has an estimated annual healthcare cost of 16.7
      billion dollars and leads to 120,000 deaths. Insufficient development in both
      medical diagnosis and treatment of sepsis has led to continued growth in reported
      cases of sepsis over the past two decades with little improvement in mortality
      statistics. Efforts over the last decade to improve diagnosis have unsuccessfully
      sought to identify a "magic bullet" proteic biomarker that provides high
      sensitivity and specificity for infectious inflammation. More recently, genetic
      methods have made tracking regulation of the genes responsible for these
      biomarkers possible, giving current research new direction in the search to
      understand how host immune response combats infection. Despite the breadth of
      research, inadequate treatment as a result of delayed diagnosis continues to
      affect approximately one fourth of septic patients. In this report we review past
      and present diagnostic methods for sepsis and their respective limitations, and
      discuss the requirements for more timely diagnosis as the next step in curtailing
      sepsis-related mortality. We also present a proposal toward revision of the
      current diagnostic paradigm to include real-time immune monitoring.

PMID- 15166108
TI  - Second-trimester maternal serum invasive trophoblast antigen: a marker for Down
      syndrome screening.

PMID- 15166109
TI  - Maternal homocysteine before conception and throughout pregnancy predicts fetal
      homocysteine and birth weight.
AB  - BACKGROUND: Increased homocysteine has been associated with pregnancy
      complications. METHODS: We investigated prospectively the effect of maternal
      homocysteine on normal pregnancy outcome. The study included 93 women and their
      offspring; 39 of the women took folic acid during the second and/or third
      trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8,
      20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded
      birth weight. RESULTS: Geometric mean (SE) maternal total homocysteine (tHcy)
      increased between 32 weeks of pregnancy and labor [7.98 (1.05) micromol/L in
      unsupplemented women and 6.26 (1.07) micromol/L in supplemented women; P <0.0001
      for both]. Fetal tHcy was lower than maternal tHcy [6.39 (1.06) micromol/L in
      unsupplemented pregnancies (P <0.0001), and 5.18 (1.06) micromol/L in
      supplemented pregnancies (P <0.05)]. Maternal tHcy was correlated from
      preconception throughout pregnancy (8 weeks, r = 0.708; 20 weeks, r = 0.637; 32
      weeks, r = 0.537; labor, r = 0.502; P <0.0001 for all time points) and with fetal
      tHcy [preconception, r = 0.255 (P <0.05); 8 weeks, r = 0.321 (P <0.01); 20 weeks,
      r = 0.469; 32 weeks, r = 0.550; labor, r = 0.624 (P <0.0001)]. Mothers in the
      highest tHcy tertile at 8 weeks of pregnancy were three times [odds ratio, 3.26
      (95% confidence interval, 1.05-10.13); P <0.05] and at labor were four times
      [3.65 (1.15-11.56); P <0.05] more likely to give birth to a neonate in the lowest
      birth weight tertile. Neonates of mothers in the highest tHcy tertile at labor
      weighed, on average, 227.98 g less than those of mothers in the low and medium
      tertiles (P = 0.014). CONCLUSIONS: Supplemented mothers had lower tHcy at labor
      than unsupplemented mothers, as did their neonates. Maternal and fetal tHcy was
      significantly correlated throughout the study. Neonates of mothers in the highest
      tertile of homocysteine weighed less.

PMID- 15166110
TI  - Measurement of urinary D- and L-2-hydroxyglutarate enantiomers by stable-isotope
      dilution liquid chromatography-tandem mass spectrometry after derivatization with
      diacetyl-L-tartaric anhydride.
AB  - BACKGROUND: The differential diagnosis of D-2-hydroxyglutaric aciduria (D-2-HGA),
      L-2-hydroxyglutaric aciduria (L-2-HGA), and the combined D/L-2-hydroxyglutaric
      aciduria (D/L-2-HGA) can be accomplished only by the measurement of the
      corresponding 2-hydroxyglutarate (2-HG). Available methods for the determination
      of D- and L-2-HG in urine are either time-consuming and expensive or have not
      been extensively validated. We aimed to develop a method for their rapid and
      sensitive measurement. METHODS: We used liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for the determination of D- and L-2-HG with stable
      isotope-labeled internal standards. Urine samples of 20 microL were mixed with
      250 microL of methanol containing the internal standards and subsequently dried
      under nitrogen. The analytes were derivatized by use of diacetyl-L-tartaric
      anhydride (DATAN) to obtain diastereomers, which were separated on an achiral C18
      HPLC column and detected by MS/MS in multiple-reaction-monitoring mode. RESULTS:
      The use of DATAN as chiral derivatization reagent provided very well separated
      peaks of the formed diastereomers of D- and L-2-HG, with a total runtime of 5
      min. The inter- and intraassay CVs for D- and L-2-HG ranged from 3.4% to 6.2%.
      Mean recoveries of D- and L-2-HG, evaluated on two concentrations, were 94%.
      Detection limit of the presented method was 20 pmol for a sample volume of 20
      microL. Method comparison of the LC-MS/MS method with a gas chromatography-mass
      spectrometry method, in which D- and L-2-HG were derivatized with R-(-)-butanol,
      showed good agreement between the two methods. CONCLUSIONS: Urinary D- and L-2-HG
      can be analyzed by MS/MS after derivatization with DATAN. The presented method
      may be suitable for the differential diagnosis of 2-HGA.

PMID- 15166111
TI  - Closed-tube genotyping with unlabeled oligonucleotide probes and a saturating DNA
      dye.
AB  - BACKGROUND: Homogeneous PCR methods for genotyping usually require fluorescently
      labeled oligonucleotide probes. Amplicon melting with the DNA dye LCGreen I was
      recently introduced as a closed-tube method of genotyping that does not require
      probes or real-time PCR. However, some single-nucleotide polymorphisms (SNPs)
      could not be completely genotyped without addition of a known genotype, and high
      resolution melting techniques were necessary. METHODS: A 3'-blocked, unlabeled
      oligonucleotide probe and the saturating dye, LCGreen I, were added to standard
      PCR reagents before amplification. After PCR, the samples were melted at 0.1-0.3
      degrees C/s in high-resolution (HR-1), high-throughput (LightTyper), and rapid
      cycle, real-time (LightCycler) instruments, and fluorescence melting curves were
      recorded. RESULTS: Derivative melting curves of the probe-target duplexes were
      characteristic of the genotype under the probe. With synthetic plasmid templates,
      all SNP base combinations could be genotyped. For human genomic DNA, the
      technique was demonstrated with mutations associated with cystic fibrosis,
      including SNPs (G542X, I506V, and F508C) and 3-bp deletions (F508del and
      I507del). CONCLUSIONS: Genotyping of SNPs and small deletions by melting analysis
      of an unlabeled probe in the presence of LCGreen I is simple and rapid. Only
      three unlabeled oligonucleotides (two primers and one probe), a saturating DNA
      dye, PCR, and a melting instrument are required. The method is closed-tube, does
      not require fluorescently labeled probes or real-time PCR, and can be completed
      in <10 min on any instrument capable of monitoring melting curves by
      fluorescence.

PMID- 15166112
TI  - Application of a newly developed ELISA for BCAR1 protein for prediction of
      clinical benefit of tamoxifen therapy in patients with advanced breast cancer.

PMID- 15166113
TI  - Cold-induced vasoconstriction: a Waltz pairing Rho-kinase signaling and alpha2
      adrenergic receptor translocation.

PMID- 15166114
TI  - Ca2+ control of transcription: can we extrapolate signaling cascades from neurons
      to vascular smooth muscle cells?

PMID- 15166115
TI  - Cardiac myosin binding protein C: its role in physiology and disease.
AB  - Myosin binding protein-C (MyBP-C) is a thick filament-associated protein
      localized to the crossbridge-containing C zones of striated muscle sarcomeres.
      The cardiac isoform is composed of eight immunoglobulin I-like domains and three
      fibronectin 3-like domains and is known to be a physiological substrate of cAMP
      dependent protein kinase. MyBP-C contributes to thick filament structure via
      interactions at its C-terminus with the light meromyosin section of the myosin
      rod and with titin. The protein also has a role in the regulation of contraction,
      due to the binding of its N-terminus to the subfragment-2 portion of myosin,
      which reduces actomyosin ATPase activity; phosphorylation abolishes this
      interaction, resulting in release of the "brake" on crossbridge cycling. Several
      structural models of the interaction of MyBP-C with myosin have been proposed,
      although its precise arrangement on the thick filament remains to be elucidated.
      Mutations in the gene encoding cardiac MyBP-C are a common cause of hypertrophic
      cardiomyopathy, and this has led to increased interest in the protein's function.
      Investigation of disease-causing mutations in domains with unknown function has
      led to further insights into the mechanism of cMyBP-C action. This Review aims to
      collate the published data on those aspects of MyBP-C that are well characterized
      and to consider new and emerging data that further define its structural and
      regulatory roles and its arrangement in the sarcomere. We also speculate on the
      mechanisms by which hypertrophic cardiomyopathy-causing truncation and missense
      mutations affect the normal functioning of the sarcomere.

PMID- 15166116
TI  - Myosin crossbridge activation of cardiac thin filaments: implications for
      myocardial function in health and disease.
AB  - At the level of the myofibrillar proteins, activation of myocardial contraction
      is thought to involve switch-like regulation of crossbridge binding to the thin
      filaments. A central feature of this view of regulation is that Ca2+ binding to
      the low-affinity (approximately 3 micromol/L) site on troponin C alters the
      interactions of proteins in the thin filament regulatory strand, which leads to
      movement of tropomyosin from its blocking position on the thin filament and
      binding of crossbridges to actin. Although Ca2+ binding is a critical step in
      initiating contraction, this event alone does not account for the activation
      dependence of contractile properties of myocardium. Instead, activation is a
      highly cooperative process in which initial crossbridge binding to the thin
      filaments recruits additional crossbridge binding to actin as well as increased
      Ca2+ binding to troponin C. This review addresses possible roles of thin filament
      cooperativity in myocardium as a process that modulates the activation dependence
      of force and the rate of force development and also possible mechanisms by which
      cooperative signals are transmitted along the thick filament. Emerging evidence
      suggests that such mechanisms could contribute to the regulation of fundamental
      mechanical properties of myocardium and alterations in regulation that underlie
      contractile disorders in diseases such as cardiomyopathies.

PMID- 15166117
TI  - Heat shock-related protein 20 (HSP20) in cardiomyocytes.

PMID- 15166118
TI  - Absence of a NPR-A gene functional deletion allele in a postmyocardial infarction
      cohort from New Zealand.

PMID- 15166119
TI  - Lactoferrin is a potent regulator of bone cell activity and increases bone
      formation in vivo.
AB  - Lactoferrin is an iron-binding glycoprotein present in epithelial secretions,
      such as milk, and in the secondary granules of neutrophils. We found it to be
      present in fractions of milk protein that stimulated osteoblast growth, so we
      assessed its effects on bone cell function. Lactoferrin produced large, dose
      related increases in thymidine incorporation in primary or cell line cultures of
      human or rat osteoblast-like cells, at physiological concentrations (1-100
      microg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also
      increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50
      70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes.
      Purified, recombinant, human, or bovine lactoferrins had similar potencies. In
      mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and
      was completely arrested by lactoferrin, 100 microg/ml, associated with decreased
      expression of receptor activator of nuclear factor-kappaB ligand. In contrast,
      lactoferrin had no effect on bone resorption by isolated mature osteoclasts.
      Lactoferrin was administered over calvariae of adult mice for 5 d. New bone
      formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg
      dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating,
      and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis.
      Lactoferrin is a potential therapeutic target in bone disorders such as
      osteoporosis and is possibly an important physiological regulator of bone growth.

PMID- 15166120
TI  - Administration of human insulin-like growth factor-binding protein-1 increases
      circulating levels of growth hormone in mice.
AB  - GH is the major regulator of circulating IGF-I, which, in return, controls
      pituitary GH secretion by negative feedback. IGF-binding protein-1 (IGFBP-1) is
      believed to modify this feedback through its effects on free IGF-I. In the
      present study we investigated the potential influence of IGFBP-1 on GH secretion
      in the absence or presence of a GH receptor antagonist (GHRA) that specifically
      blocks peripheral GH action. We administered human (h) IGFBP-1 and GHRA to mice
      alone or in combination for 2 or 7 d. GHRA was administered in a dose previously
      shown to block GH action without an effect on circulating GH or IGF-I levels.
      hIGFBP-1 administration increased stimulated circulating GH levels and serum
      total IGF-I and IGFBP-3 levels. Coadministration of GHRA abolished the hIGFBP-1
      induced increase in serum IGF-I and IGFBP-3 levels, whereas stimulated GH levels
      remained increased. Free IGF-I levels in serum were unchanged in all treatment
      groups. In conclusion, GH serum levels increased in response to hIGFBP-1
      administration, even in the setting of normal IGF-I levels. This finding suggests
      a direct involvement of IGFBP-1 in GH secretion.

PMID- 15166121
TI  - Antiapoptotic effects of leptin in human neuroblastoma cells.
AB  - Many factors regulate nervous system development, including complex cross-talk
      between local neuroendocrine systems. The adipocyte-secreted hormone leptin,
      mainly known for its key roles in nutrition and reproductive balance, may also be
      involved in neuroanatomical organization, myelination processes, and
      neuronal/glia maturation. SK-N-SH-SY5Y neuroblastoma cells were employed as an in
      vitro model of human neuronal cells to determine whether leptin exerts
      neuroprotective activities. We show that SH-SY5Y cells express leptin, the long
      and short isoforms of the leptin receptor (ObRl, ObRs). In SH-SY5Y cells, leptin
      induced signal transducer and activator of transcription (STAT)-3 phosphorylation
      and suppressor of cytokine signaling-3 mRNA expression. Leptin dose-dependently
      increased cell number (up to 200% at 1 microm by 48 h, P < 0.01), and at 24-48 h,
      leptin at 100 nm increased SH-SY5Y cell number by 30-50%, respectively. SH-SY5Y
      cell viability was reduced in serum-free conditions at 24 h, and addition of
      leptin at 100 nm significantly reduced apoptosis by approximately 20% (P <
      0.001). Leptin's antiapoptotic activity required Janus kinase/STAT, MAPK, and
      phosphatidylinositol-3-kinase activation because the antiapoptotic effects of
      leptin were abolished, and caspase-3 immunoreactivity increased in the presence
      of the specific blockers AG490, U0126, or LY294002. Gene array demonstrated that
      leptin inhibits apoptosis via potent down-regulation of caspase-10 and TNF
      related apoptosis-inducing ligand. Our data thus demonstrate, for the first time,
      that leptin stimulates, in a time- and dose-dependent manner, neuroblastoma cell
      proliferation and that the underlying mechanisms involve suppression of apoptosis
      via the Janus kinase-STAT, phosphatidylinositol-3 kinase, and MAPK pathways that
      culminate altogether in the down-regulation of the apoptotic factors caspase-10
      and TNF-related apoptosis-inducing ligand.

PMID- 15166123
TI  - Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the
      transport of thyroxine across the blood-brain barrier.
AB  - The present study was aimed at investigating the involvement of mouse organic
      anion transporting polypeptide 14 (mOatp14) in the uptake of T4 across the blood
      brain barrier. Functional expression of mOatp14 in HEK293 cells revealed that T4
      and rT3 are high affinity substrates of mOatp14 (Michaelis constant, 0.34 and
      0.46 microm, respectively), and the specific uptake of T3 was 4-fold less than
      that of T4 and rT3. Taurocholate, probenecid, and estrone-3-sulfate were moderate
      inhibitors for mOatp14, whereas digoxin (substrate of Oatp2), benzylpenicillin
      (substrate of Oat3), and large neutral amino acids had no effect. mOatp14 is
      widely expressed throughout the brain, except for the cerebellum. The expression
      of mOatp14 in the isolated brain capillaries and the choroid plexus was shown by
      Western blot. The uptake clearance of T4 by the cerebral cortex determined using
      the in situ brain perfusion technique in mice was 580 microl/min.g tissue, 3-fold
      greater than that by the cerebellum, and a saturable component (Michaelis
      constant, 1.0 microm) accounts for the major fraction of the total uptake.
      Taurocholate inhibited the uptake of T4 by the cerebral cortex completely, but
      the inhibition by estrone-3-sulfate was partial (50%). These results suggest that
      transporters play a predominant role in the delivery of T4 to the brain, and
      mOatp14 accounts for estrone-3-sulfate inhibitable fraction, at least partly. The
      absence of inhibition by digoxin, benzylpenicillin, leucine, and 2-aminobicyclo
      (2,2,1)-heptane-2-carboxylic acid for the uptake of T4 by the cerebral cortex
      suggests the presence of other unknown transporter for T4 uptake by the brain.
      Immunohistochemical staining revealed basolateral localization of mOatp14 in the
      choroid plexus in which it may also play a role in T4 uptake.

PMID- 15166122
TI  - Increased insulin sensitivity in paternal Gnas knockout mice is associated with
      increased lipid clearance.
AB  - The G protein alpha-subunit Gsalpha is required for hormone-stimulated cAMP
      generation. The Gsalpha gene Gnas is a complex gene with multiple imprinted gene
      products. Mice with heterozygous disruption of the Gnas paternal allele (+/p-)
      are partially Gsalpha deficient and totally deficient in XLalphas, a
      neuroendocrine-specific Gsalpha isoform that is expressed only from the paternal
      Gnas allele. We previously showed that these mice are hypermetabolic and lean and
      have increased insulin sensitivity. We now performed hyperinsulinemic-euglycemic
      clamp studies, which confirmed the markedly increased whole body insulin
      sensitivity in +/p- mice. +/p- mice had 1.4-, 7- and 3.8-fold increases in
      insulin-stimulated glucose uptake in muscle and white and brown adipose tissue,
      respectively, and markedly suppressed endogenous glucose production from the
      liver. This was associated with increased phosphorylation of insulin receptor and
      a downstream effector (Akt kinase) in both liver and muscle in response to
      insulin. Triglycerides cleared more rapidly in +/p- mice after a bolus
      administered by gavage. This was associated with decreased liver and muscle
      triglyceride content and increased muscle acyl-CoA oxidase mRNA expression.
      Resistin and adiponectin were overexpressed in white adipose tissue of +/p- mice,
      although there was no difference in serum adiponectin levels. The lean phenotype
      and increased insulin sensitivity observed in +/p- mice is likely a consequence
      of increased lipid oxidation in muscle and possibly other tissues. Further
      studies will clarify whether XLalphas deficiency is responsible for these effects
      and if so, the mechanism by which XLalphas deficiency leads to this metabolic
      phenotype.

PMID- 15166124
TI  - Disruption of glucose sensing and insulin secretion by ribozyme Kir6.2-gene
      targeting in insulin-secreting cells.
AB  - The ATP-sensitive K+ (KATP) channel, composed of Kir6.2 and sulfonylurea receptor
      (SUR1), in pancreatic beta-cells is believed to serve as a metabolic sensor
      regulating insulin secretion according to glucose levels. Thus, genetic
      disruption of Kir6.2 expression may impair KATP channel function in glucose
      sensing and insulin secretion. Here we show evidence obtained from functional
      genetic assays supporting this hypothesis. To avoid adaptive cellular mechanisms
      in transgenic preparations, we designed a hammerhead ribozyme that specifically
      targeted the Kir6.2 mRNA at serine 78. The Kir6.2-ribozyme was constructed in an
      adenoviral vector and expressed in insulin-secreting RINm5F cells. Both RT-PCR
      and Northern blot analyses showed that Kir6.2 transcripts were significantly
      reduced with a Kir6.2-ribozyme treatment. Whole-cell patch-clamp studies
      indicated that the Kir6.2-ribozyme treatment lowered KATP channel density by 66%.
      In response to higher glucose challenge, insulin release from the RINm5F cells
      dropped by approximately 20% in a transfection dose of 0.7 multiplicity of
      infection, and by 30-40% in a dose of 2.7 multiplicity of infection. These
      results therefore indicate that KATP channels play an important role in glucose
      sensing and insulin secretion, and ribozyme Kir6.2-gene targeting is an effective
      approach for selective inhibition of functional expression of KATP channels.

PMID- 15166126
TI  - In vitro maturation and fertilization of oocytes from an intact ovary of a
      surgically treated patient with endometrial carcinoma: case report.
AB  - Polycystic ovary syndrome (PCOS) with prolonged anovulation had resulted in
      endometrial carcinoma in a 43-year-old woman. Since she and her husband did not
      share common biological children, they requested fertility preservation. Due to
      the woman's age, high dose progesterone and postponing surgery were both
      considered inappropriate. We therefore proposed oocyte retrieval from the ovaries
      removed by staging laparotomy followed by in vitro maturation and ICSI. Surrogacy
      could then enable a future pregnancy. Fourteen of 17 (82%) retrieved oocytes
      matured in vitro. Following ICSI, eight embryos (two at the pronuclear stage and
      six cleaved) were cryopreserved. To the best of our knowledge, this is the first
      report of oocyte aspiration, maturation and fertilization from an ovary removed
      by laparotomy.

PMID- 15166125
TI  - Dehydration-induced cross-regulation of apelin and vasopressin immunoreactivity
      levels in magnocellular hypothalamic neurons.
AB  - Apelin, a neuropeptide recently identified as the endogenous ligand for the G
      protein-coupled receptor APJ, is highly concentrated in brain structures involved
      in the control of body fluid homeostasis including the supraoptic (SON) and
      paraventricular (PVN) hypothalamic nuclei. To clarify the implication of apelin
      in the regulation of water balance, we sought to determine whether apelin
      colocalized with arginine vasopressin (AVP) in the rat SON and PVN. We also
      investigated the effects of water deprivation on the levels of apelin within
      these two nuclei by comparison with those of AVP. Using dual immunolabeling
      confocal microscopy, we found that a large proportion of apelin-immunoreactive
      neurons colocalized AVP within both the SON and PVN, but that the two peptides
      were segregated within distinct subcellular compartments inside these cells. Both
      the number and labeling intensity of magnocellular apelin-immunoreactive cells
      increased significantly after 24- or 48-h dehydration, whereas the number and
      labeling density of AVP-immunoreactive neurons significantly decreased. The
      dehydration-induced increase in apelin immunoreactivity was markedly diminished
      by central injection of a selective vasopressin-1 receptor antagonist.
      Conversely, the effect of dehydration was mimicked by a 16-min
      intracerebroventricular infusion of AVP, again in a vasopressin-1 receptor
      antagonist-reversible manner. These results provide additional evidence for the
      involvement of the neuropeptide apelin in the control of body fluid homeostasis.
      They further suggest that the dehydration-induced release of AVP from
      magnocellular hypothalamic neurons may be responsible for the observed increase
      in immunoreactive apelin levels within the same neurons and thus that the release
      of one peptide may block that of another peptide synthesized in the same cells.

PMID- 15166127
TI  - Trisomic pregnancy and the oocyte pool.
AB  - BACKGROUND: We tested the hypothesis that trisomy risk is increased for women
      with fewer oocytes (older ovarian age) than other women of the same chronological
      age. METHODS: Our study compared three indicators of ovarian age-number of antral
      follicles, level of dimeric inhibin B, level of FSH-among women who had trisomic
      pregnancy losses (n = 54) with those among women who had other losses (24 with
      other chromosomally abnormal loses, 21 with chromosomally normal losses) or who
      had chromosomally normal births (n = 65). RESULTS: Ovarian age indicators did not
      differ between women with trisomic spontaneous abortions and the three comparison
      groups. Compared with live birth controls, adjusting for chronological age, we
      estimate that, on average, among trisomy cases the geometric means of 1 +
      follicle count, inhibin B and FSH are about 7.5% higher, 16.6% higher and 5.5%
      lower, respectively, with all 95% confidence intervals including zero. The sample
      size was sufficient to detect moderate differences (0.52 standard errors of
      regression) between trisomy cases and live birth controls. CONCLUSIONS: Although
      our data do not support our hypothesis, they leave open the possibility that
      changes in follicular development unrelated to the size of the oocyte pool
      influence abnormal chromosome segregation.

PMID- 15166128
TI  - An economic comparison of a laparoscopic electrocautery strategy and ovulation
      induction with recombinant FSH in women with clomiphene citrate-resistant
      polycystic ovary syndrome.
AB  - BACKGROUND: Recombinant FSH (rFSH) is the current standard treatment for
      ovulation induction in women with polycystic ovary syndrome (PCOS) that do not
      respond to clomiphene citrate. Ovulation induction with rFSH is known to be
      costly due to the necessity of daily injections and intensive monitoring. An
      alternative strategy, starting with electrocautery of the ovaries, may be a less
      costly option. METHODS: An economic evaluation was set up alongside a multicentre
      randomized clinical trial comparing laparoscopic electrocautery of the ovaries,
      followed by clomiphene citrate and rFSH when anovulation persisted, and treatment
      with rFSH in 168 women with clomiphene citrate-resistant PCOS. Data on resources
      used for treatment and productivity loss were collected prospectively up to an
      eventual ongoing pregnancy with a time horizon of 12 months. RESULTS: At 12
      months the ongoing pregnancy rates were 67% for both the electrocautery strategy
      and rFSH treatment. Mean total costs per woman were 5308 euros for the
      electrocautery strategy and 5925 euros for treatment with rFSH, resulting in a
      mean difference of 617 (95% CI: -382 euros to 1614 euros). CONCLUSIONS: The total
      treatment costs up to an ongoing pregnancy are comparable for rFSH treatment and
      an alternative strategy starting with electrocautery. Due to a lower number of
      multiple pregnancies, the electrocautery strategy can be expected to result in
      lower total costs when costs of the delivery are included.

PMID- 15166129
TI  - A combination of interleukin-6 and its soluble receptor impairs sperm motility:
      implications in infertility associated with endometriosis.
AB  - BACKGROUND: We previously reported that the level of interleukin (IL)-6 is
      increased in the peritoneal fluid of women with endometriosis. This study was
      undertaken to assess the effects of IL-6 and soluble IL-6 receptor (sIL-6R) on in
      vitro sperm motility. METHODS: Sperm (n = 20) were cultured with IL-6 or sIL-6R,
      or with a combination of both. After 24 h cultures, sperm motility was evaluated
      using a computer-assisted semen analysis system. Gene and protein expressions of
      IL-6, IL-6 receptor (IL-6R), and glycoprotein 130 (gp130) were examined in sperm
      by RT-PCR analysis and western blot analysis. RESULTS: Addition of IL-6 or sIL-6R
      individually to the culture media had no affect on sperm motion. However, adding
      a combination of IL-6 and sIL-6R dose-dependently reduced the percentage of
      motile and rapidly moving sperm. Adding anti-IL-6R antibody abolished these
      adverse effects. Sperm expressed the gp130 gene and protein, but not IL-6 or IL
      6R. CONCLUSIONS: A combination of IL-6 and sIL-6R may be associated with gp130
      expressed in the sperm and reduce sperm motility. IL-6 and sIL-6R may contribute
      to the pathogenesis of endometriosis-associated infertility.

PMID- 15166130
TI  - Complete oocyte activation failure after ICSI can be overcome by a modified
      injection technique.
AB  - BACKGROUND: Complete fertilization failure after ICSI is a rare event, and it may
      happen repeatedly even in cases of normal sperm parameters and good ovarian
      response. In these cycles, alternative ICSI techniques may prove useful. METHODS:
      Our modified ICSI (mICSI) is characterized by aspiration close to the opposite
      membrane (the region of the mitochondria with a high inner mitochondrial membrane
      potential) which is followed by central deposition of the sperm. The method was
      applied prospectively to ICSI cycles of patients with a history of complete
      fertilization failure in previous ICSI cycles. In parallel, mICSI was compared
      with conventional ICSI in terms of further preimplantation development and
      treatment outcome. RESULTS: In patients with previous ICSI failures using
      conventional ICSI (no 2Pn zygotes out of 70 oocytes that had been injected)
      application of mICSI led to adequate fertilization (53.6%) and pregnancy rates
      (33.3%) (P < 0.001; P < 0.01). In patients without previous failed fertilization,
      no improvement in the rates of fertilization, blastocyst formation, implantation
      or clinical pregnancy could be seen. CONCLUSIONS: Our data indicate that the
      present version of ICSI is a reliable alternative to conventional ICSI. However,
      although it overcomes oocyte-dependent activation failure, routine application
      does not improve the overall results.

PMID- 15166131
TI  - Interferon-gamma gene dinucleotide (CA) repeat and interleukin-4 promoter region
      (-590C/T) polymorphisms in Japanese patients with endometriosis.
AB  - BACKGROUND: Endometriosis is a multifactorial disease with possible genetic
      predisposition and involvement of environmental factors in its pathogenesis.
      Cytokines may play important roles in the pathogenesis of endometriosis. The aim
      of this study was to investigate whether the interferon-gamma gene (IFNG) CA
      repeat and interleukin-4 (IL-4) promoter region (-590C/T) polymorphisms may be
      responsible in part for genetic susceptibility to endometriosis. METHODS: IFNG CA
      repeat and IL-4 -590C/T polymorphisms were determined for 185 patients with
      endometriosis and 176 healthy fertile women by quantitative genescan technology
      and PCR-restriction fragment length polymorphism analysis, respectively. Patients
      with endometriosis were analysed further according to their stage of disease, the
      presence or absence of chocolate cysts and whether or not their disease was
      associated with adenomyosis and/or lyomyomata. RESULTS: The global IFNG allele
      frequencies in the patients with endometriosis were significantly different from
      those in the control women (chi2 = 12.964, 6 df, P = 0.0436). The difference was
      due to an increase of the a13 (114 bp) allele in patients with endometriosis
      (chi2 = 10.222, P = 0.0088, corrected P = 0.0352, odds ratio = 1.48, 95%
      confidence interval = 1.10-1.98). There were no differences in IL-4 -590C/T
      genotypes and allele frequencies between control women and all patients with
      endometriosis or between control women and each subgroup of patients with
      endometriosis. CONCLUSION: The results suggest that the IFNG CA-repeat
      polymorphism is associated with susceptibility to endometriosis in a Japanese
      population.

PMID- 15166132
TI  - Sickle-cell anemia hemoglobin: the molecular biology of the first "molecular
      disease"--the crucial importance of serendipity.

PMID- 15166133
TI  - Phenotypic plasticity in bacterial plasmids.
AB  - Plasmid pB15 was previously shown to evolve increased horizontal (infectious)
      transfer at the expense of reduced vertical (intergenerational) transfer and vice
      versa, a key trade-off assumed in theories of parasite virulence. Whereas the
      models predict that susceptible host abundance should determine which mode of
      transfer is selectively favored, host density failed to mediate the trade-off in
      pB15. One possibility is that the plasmid's transfer deviates from the assumption
      that horizontal spread (conjugation) occurs in direct proportion to cell density.
      I tested this hypothesis using Escherichia coli/pB15 associations in laboratory
      serial culture. Contrary to most models of plasmid transfer kinetics, my data
      show that pB15 invades static (nonshaking) bacterial cultures only at
      intermediate densities. The results can be explained by phenotypic plasticity in
      traits governing plasmid transfer. As cells become more numerous, the plasmid's
      conjugative transfer unexpectedly declines, while the trade-off between
      transmission routes causes vertical transfer to increase. Thus, at intermediate
      densities the plasmid's horizontal transfer can offset selection against plasmid
      bearing cells, but at high densities pB15 conjugates so poorly that it cannot
      invade. I discuss adaptive vs. nonadaptive causes for the phenotypic plasticity,
      as well as potential mechanisms that may lead to complex transfer dynamics of
      plasmids in liquid environments.

PMID- 15166134
TI  - An essential role for the Saccharomyces cerevisiae DEAD-box helicase DHH1 in G1/S
      DNA-damage checkpoint recovery.
AB  - The eukaryotic cell cycle displays a degree of plasticity in its regulation; cell
      cycle progression can be transiently arrested in response to environmental
      stresses. While the signaling pathways leading to cell cycle arrest are beginning
      to be well understood, the regulation of the release from arrest has not been
      well characterized. Here we show that DHH1, encoding a DEAD-box RNA helicase
      orthologous to the human putative proto-oncogene p54/RCK, is important in release
      from DNA-damage-induced cell cycle arrest at the G1/S checkpoint. DHH1 mutants
      are not defective for DNA repair and recover normally from the G2/M and
      replication checkpoints, suggesting a specific function for Dhh1p in recovery
      from G1/S checkpoint arrest. Dhh1p has been suggested to play a role in
      partitioning mRNAs between translatable and nontranslatable pools, and our
      results implicate this modulation of mRNA metabolism in the recovery from G1/S
      cell cycle arrest following DNA damage. Furthermore, the high degree of
      conservation between DHH1 and its human ortholog suggests that this mechanism is
      conserved among all eukaryotes and potentially important in human disease.

PMID- 15166135
TI  - Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a
      synthetic interaction network and altered sensitivity to caspofungin.
AB  - Large-scale screening of genetic and chemical-genetic interactions was used to
      examine the assembly and regulation of beta-1,3-glucan in Saccharomyces
      cerevisiae. Using the set of deletion mutants in approximately 4600 nonessential
      genes, we scored synthetic interactions with genes encoding subunits of the beta
      1,3-glucan synthase (FKS1, FKS2), the glucan synthesis regulator (SMI1/KNR4), and
      a beta-1,3-glucanosyltransferase (GAS1). In the resulting network, FKS1, FKS2,
      GAS1, and SMI1 are connected to 135 genes in 195 interactions, with 26 of these
      genes also interacting with CHS3 encoding chitin synthase III. A network core of
      51 genes is multiply connected with 112 interactions. Thirty-two of these core
      genes are known to be involved in cell wall assembly and polarized growth, and 8
      genes of unknown function are candidates for involvement in these processes. In
      parallel, we screened the yeast deletion mutant collection for altered
      sensitivity to the glucan synthase inhibitor, caspofungin. Deletions in 52 genes
      led to caspofungin hypersensitivity and those in 39 genes to resistance.
      Integration of the glucan interaction network with the caspofungin data indicates
      an overlapping set of genes involved in FKS2 regulation, compensatory chitin
      synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway.

PMID- 15166136
TI  - In vivo analysis of synaptonemal complex formation during yeast meiosis.
AB  - During meiotic prophase a synaptonemal complex (SC) forms between each pair of
      homologous chromosomes and is believed to be involved in regulating
      recombination. Studies on SCs usually destroy nuclear architecture, making it
      impossible to examine the relationship of these structures to the rest of the
      nucleus. In Saccharomyces cerevisiae the meiosis-specific Zip1 protein is found
      throughout the entire length of each SC. To analyze the formation and structure
      of SCs in living cells, a functional ZIP1::GFP fusion was constructed and
      introduced into yeast. The ZIP1::GFP fusion produced fluorescent SCs and rescued
      the spore lethality phenotype of zip1 mutants. Optical sectioning and
      fluorescence deconvolution light microscopy revealed that, at zygotene, SC
      assembly was initiated at foci that appeared uniformly distributed throughout the
      nuclear volume. At early pachytene, the full-length SCs were more likely to be
      localized to the nuclear periphery while at later stages the SCs appeared to
      redistribute throughout the nuclear volume. These results suggest that SCs
      undergo dramatic rearrangements during meiotic prophase and that pachytene can be
      divided into two morphologically distinct substages: pachytene A, when SCs are
      perinuclear, and pachytene B, when SCs are uniformly distributed throughout the
      nucleus. ZIP1::GFP also facilitated the enrichment of fluorescent SC and the
      identification of meiosis-specific proteins by MALDI-TOF mass spectroscopy.

PMID- 15166137
TI  - MrpL36p, a highly diverged L31 ribosomal protein homolog with additional
      functional domains in Saccharomyces cerevisiae mitochondria.
AB  - Translation in mitochondria utilizes a large complement of ribosomal proteins.
      Many mitochondrial ribosomal components are clearly homologous to eubacterial
      ribosomal proteins, but others appear unique to the mitochondrial system. A
      handful of mitochondrial ribosomal proteins appear to be eubacterial in origin
      but to have evolved additional functional domains. MrpL36p is an essential
      mitochondrial ribosomal large-subunit component in Saccharomyces cerevisiae.
      Increased dosage of MRPL36 also has been shown to suppress certain types of
      translation defects encoded within the mitochondrial COX2 mRNA. A central domain
      of MrpL36p that is similar to eubacterial ribosomal large-subunit protein L31 is
      sufficient for general mitochondrial translation but not suppression, and
      proteins bearing this domain sediment with the ribosomal large subunit in sucrose
      gradients. In contrast, proteins lacking the L31 domain, but retaining a novel N
      terminal sequence and a C-terminal sequence with weak similarity to the
      Escherichia coli signal recognition particle component Ffh, are sufficient for
      dosage suppression and do not sediment with the large subunit of the ribosome.
      Interestingly, the activity of MrpL36p as a dosage suppressor exhibits gene and
      allele specificity. We propose that MrpL36p represents a highly diverged L31
      homolog with derived domains functioning in mRNA selection in yeast mitochondria.

PMID- 15166139
TI  - Genetic interactions with C-terminal domain (CTD) kinases and the CTD of RNA Pol
      II suggest a role for ESS1 in transcription initiation and elongation in
      Saccharomyces cerevisiae.
AB  - Ess1 is an essential prolyl isomerase that binds the C-terminal domain (CTD) of
      Rpb1, the large subunit of RNA polymerase II. Ess1 is proposed to control
      transcription by isomerizing phospho-Ser-Pro peptide bonds within the CTD repeat.
      To determine which step(s) in the transcription cycle might require Ess1, we
      examined genetic interactions between ESS1 and genes encoding the known CTD
      kinases (KIN28, CTK1, BUR1, and SRB10). Although genetic interactions were
      identified between ESS1 and all four kinases, the clearest interactions were with
      CTK1 and SRB10. Reduced dosage of CTK1 rescued the growth defect of ess1(ts)
      mutants, while overexpression of CTK1 enhanced the growth defects of ess1(ts)
      mutants. Deletion of SRB10 suppressed ess1(ts) and ess1Delta mutants. The
      interactions suggest that Ess1 opposes the functions of these kinases, which are
      thought to function in preinitiation and elongation. Using a series of CTD
      substitution alleles, we also identified Ser5-Pro6 as a potential target for Ess1
      isomerization within the first "half" of the CTD repeats. On the basis of the
      results, we suggest a model in which Ess1-directed conformational changes promote
      dephosphorylation of Ser5 to stimulate preinitiation complex formation and,
      later, to inhibit elongation.

PMID- 15166138
TI  - A novel gene, msa1, inhibits sexual differentiation in Schizosaccharomyces pombe.
AB  - Sexual differentiation in the fission yeast Schizosaccharomyces pombe is
      triggered by nutrient starvation or by the presence of mating pheromones. We
      identified a novel gene, msa1, which encodes a 533-aa putative RNA-binding
      protein that inhibits sexual differentiation. Disruption of the msa1 gene caused
      cells to hypersporulate. Intracellular levels of msa1 RNA and Msa1 protein
      diminished after several hours of nitrogen starvation. Genetic analysis suggested
      that the function of msa1 is independent of the cAMP pathway and stress
      responsive pathway. Deletion of the ras1 gene in diploid cells inhibited
      sporulation and in haploid cells decreased expression of mating-pheromone-induced
      genes such as mei2, mam2, ste11, and rep1; simultaneous deletion of msa1 reversed
      both phenotypes. Overexpression of msa1 decreased activated Ras1(Val17)-induced
      expression of mam2. Phenotypic hypersporulation was similar between cells with
      deletion of only rad24 and both msa1 and rad24, but simultaneous deletion of msa1
      and msa2/nrd1 additively increased hypersporulation. Therefore, we suggest that
      the primary function of Msa1 is to negatively regulate sexual differentiation by
      controlling the expression of Ste11-regulated genes, possibly through the
      pheromone-signaling pathway.

PMID- 15166140
TI  - Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar
      protein sorting.
AB  - Conditional cdc1(Ts) mutants of S. cerevisiae arrest with a phenotype similar to
      that exhibited by Mn(2+)-depleted cells. Sequence similarity between Cdc1p and a
      class of Mn(2+)-dependent phosphoesterases, as well as the observation that
      conditional cdc1(Ts) growth can be ameliorated by Mn(2+) supplement, suggests
      that Cdc1p activity is sensitive to intracellular Mn(2+) levels. This article
      identifies several previously uncharacterized cdc1(Ts) suppressors as class E vps
      (vacuolar protein sorting) mutants and shows that these, as well as other vps
      mutants, accumulate high levels of intracellular Mn(2+). Yeast VPS genes play a
      role in delivery of membrane transporters to the vacuole for degradation, and we
      show that the vps mutants accumulate elevated levels of the high-affinity Mn(2+)
      transporter Smf1p. cdc1(Ts) conditional growth is also alleviated by mutations,
      including doa4 and ubc4, that compromise protein ubiquitination, and these
      ubiquitination defects are associated with Smf1p accumulation. Epistasis studies
      show that these suppressors require functional Smf1p to alleviate the cdc1(Ts)
      growth defect, whereas Smf1p is dispensable for cdc1(Ts) suppression by a
      mutation (cos16/per1) that does not influence intracellular Mn(2+) levels.
      Because Smf1p is ubiquitinated in vivo, we propose that Smf1p is targeted to the
      vacuole for degradation by ubiquitination-dependent protein sorting.

PMID- 15166141
TI  - A genetic selection for circadian output pathway mutations in Neurospora crassa.
AB  - In most organisms, circadian oscillators regulate the daily rhythmic expression
      of clock-controlled genes (ccgs). However, little is known about the pathways
      between the circadian oscillator(s) and the ccgs. In Neurospora crassa, the frq,
      wc-1, and wc-2 genes encode components of the frq-oscillator. A functional frq
      oscillator is required for rhythmic expression of the morning-specific ccg-1 and
      ccg-2 genes. In frq-null or wc-1 mutant strains, ccg-1 mRNA levels fluctuate near
      peak levels over the course of the day, whereas ccg-2 mRNA remains at trough
      levels. The simplest model that fits the above observations is that the frq
      oscillator regulates a repressor of ccg-1 and an activator of ccg-2. We utilized
      a genetic selection for mutations that affect the regulation of ccg-1 and ccg-2
      by the frq-oscillator. We find that there is at least one mutant strain, COP1-1
      (circadian output pathway derived from ccg-1), that has altered expression of ccg
      1 mRNA, but normal ccg-2 expression levels. However, the clock does not appear to
      simply regulate a repressor of ccg-1 and an activator of ccg-2 in two independent
      pathways, since in our selection we identified three mutant strains, COP1-2, COP1
      3, and COP1-4, in which a single mutation in each strain affects the expression
      levels and rhythmicity of both ccg-1 and ccg-2.

PMID- 15166142
TI  - Properties of unpaired DNA required for efficient silencing in Neurospora crassa.
AB  - The presence of unpaired copies of a gene during meiosis triggers silencing of
      all copies of the gene in the diploid ascus cell of Neurospora. This phenomenon
      is called meiotic silencing and on the basis of genetic studies appears to be a
      post-transcriptional gene silencing (PTGS) mechanism. Previously, meiotic
      silencing was defined to be induced by the presence of a DNA region lacking an
      identical segment in the homologous chromosome. However, the determinants of
      unpaired DNA remained a mystery. Using the Ascospore maturation-1 (Asm-1) gene,
      we defined what needs to be "unpaired" to silence a gene. For efficient
      silencing, an unpaired region of DNA needs to be of a sufficient size and contain
      homology to the reporter transcript. The greater the size of the loop and the
      larger the homology to the reporter transcript, the better the resulting meiotic
      silencing is. Conversely, regions not containing homology to the transcript,
      e.g., intergenic regions, did not silence the reporter. Surprisingly, unpaired
      fragments lacking a canonical promoter silenced the reporter. Additionally, we
      detected the unpairing-dependent loss of a transcript during meiotic silencing.
      Our observations further support a PTGS mechanism for meiotic silencing and offer
      insight into the evolutionary consequences resulting from this novel meiotic
      checkpoint.

PMID- 15166143
TI  - Altering a gene involved in nuclear distribution increases the repeat-induced
      point mutation process in the fungus Podospora anserina.
AB  - Repeat-induced point mutation (RIP) is a homology-dependent gene-silencing
      mechanism that introduces C:G-to-T:A transitions in duplicated DNA segments. Cis
      duplicated sequences can also be affected by another mechanism called premeiotic
      recombination (PR). Both are active over the sexual cycle of some filamentous
      fungi, e.g., Neurospora crassa and Podospora anserina. During the sexual cycle,
      several developmental steps require precise nuclear movement and positioning, but
      connections between RIP, PR, and nuclear distributions have not yet been
      established. Previous work has led to the isolation of ami1, the P. anserina
      ortholog of the Aspergillus nidulans apsA gene, which is required for nuclear
      positioning. We show here that ami1 is involved in nuclear distribution during
      the sexual cycle and that alteration of ami1 delays the fruiting-body
      development. We also demonstrate that ami1 alteration affects loss of transgene
      functions during the sexual cycle. Genetically linked multiple copies of
      transgenes are affected by RIP and PR much more frequently in an ami1 mutant
      cross than in a wild-type cross. Our results suggest that the developmental
      slowdown of the ami1 mutant during the period of RIP and PR increases time
      exposure to the duplication detection system and thus increases the frequency of
      RIP and PR.

PMID- 15166144
TI  - Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to
      hyperosmotic environments.
AB  - The molecular mechanisms that enable multicellular organisms to sense and
      modulate their responses to hyperosmotic environments are poorly understood.
      Here, we employ Caenorhabditis elegans to characterize the response of a
      multicellular organism to osmotic stress and establish a genetic screen to
      isolate mutants that are osmotic stress resistant (OSR). In this study, we
      describe the cloning of a novel gene, osr-1, and demonstrate that it regulates
      osmosensation, adaptation, and survival in hyperosmotic environments. Whereas
      wild-type animals exposed to hyperosmotic conditions rapidly lose body volume,
      motility, and viability, osr-1(rm1) mutant animals maintain normal body volume,
      motility, and viability even upon chronic exposures to high osmolarity
      environments. In addition, osr-1(rm1) animals are specifically resistant to
      osmotic stress and are distinct from previously characterized osmotic avoidance
      defective (OSM) and general stress resistance age-1(hx546) mutants. OSR-1 is
      expressed in the hypodermis and intestine, and expression of OSR-1 in hypodermal
      cells rescues the osr-1(rm1) phenotypes. Genetic epistasis analysis indicates
      that OSR-1 regulates survival under osmotic stress via CaMKII and a conserved p38
      MAP kinase signaling cascade and regulates osmotic avoidance and resistance to
      acute dehydration likely by distinct mechanisms. We suggest that OSR-1 plays a
      central role in integrating stress detection and adaptation responses by invoking
      multiple signaling pathways to promote survival under hyperosmotic environments.

PMID- 15166145
TI  - DNA variability and divergence at the notch locus in Drosophila melanogaster and
      D. simulans: a case of accelerated synonymous site divergence.
AB  - DNA diversity in two segments of the Notch locus was surveyed in four populations
      of Drosophila melanogaster and two of D. simulans. In both species we observed
      evidence of non-steady-state evolution. In D. simulans we observed a significant
      excess of intermediate frequency variants in a non-African population. In D.
      melanogaster we observed a disparity between levels of sequence polymorphism and
      divergence between one of the Notch regions sequenced and other neutral X
      chromosome loci. The striking feature of the data is the high level of synonymous
      site divergence at Notch, which is the highest reported to date. To more
      thoroughly investigate the pattern of synonymous site evolution between these
      species, we developed a method for calibrating preferred, unpreferred, and equal
      synonymous substitutions by the effective (potential) number of such changes. In
      D. simulans, we find that preferred changes per "site" are evolving significantly
      faster than unpreferred changes at Notch. In contrast we observe a significantly
      faster per site substitution rate of unpreferred changes in D. melanogaster at
      this locus. These results suggest that positive selection, and not simply
      relaxation of constraint on codon bias, has contributed to the higher levels of
      unpreferred divergence along the D. melanogaster lineage at Notch.

PMID- 15166147
TI  - The Zuker collection: a resource for the analysis of autosomal gene function in
      Drosophila melanogaster.
AB  - The majority of genes of multicellular organisms encode proteins with functions
      that are not required for viability but contribute to important physiological
      functions such as behavior and reproduction. It is estimated that 75% of the
      genes of Drosophila melanogaster are nonessential. Here we report on a strategy
      used to establish a large collection of stocks that is suitable for the recovery
      of mutations in such genes. From approximately 72,000 F(3) cultures segregating
      for autosomes heavily treated with ethyl methanesulfonate (EMS), approximately
      12,000 lines in which the treated second or third chromosome survived in
      homozygous condition were selected. The dose of EMS induced an estimated rate of
      1.2-1.5 x 10(-3) mutations/gene and predicts five to six nonessential gene
      mutations per chromosome and seven to nine alleles per locus in the samples of
      6000 second chromosomes and 6000 third chromosomes. Due to mosaic mutations
      induced in the initial exposure to the mutagen, many of the lines are segregating
      or are now fixed for lethal mutations on the mutagenized chromosome. The features
      of this collection, known as the Zuker collection, make it a valuable resource
      for forward and reverse genetic screens for mutations affecting a wide array of
      biological functions.

PMID- 15166146
TI  - Bipartite inhibition of Drosophila epidermal growth factor receptor by the
      extracellular and transmembrane domains of Kekkon1.
AB  - In Drosophila, signaling by the epidermal growth factor receptor (EGFR) is
      required for a diverse array of developmental decisions. Essential to these
      decisions is the precise regulation of the receptor's activity by both
      stimulatory and inhibitory molecules. To better understand the regulation of EGFR
      activity we investigated inhibition of EGFR by the transmembrane protein Kekkon1
      (Kek1). Kek1 encodes a molecule containing leucine-rich repeats (LRR) and an
      immunoglobulin (Ig) domain and is the founding member of the Drosophila Kekkon
      family. Here we demonstrate with a series of Kek1-Kek2 chimeras that while the
      LRRs suffice for EGFR binding, inhibition in vivo requires the Kek1
      juxta/transmembrane region. We demonstrate directly, and using a series of Kek1
      EGFR chimeras, that Kek1 is not a phosphorylation substrate for the receptor in
      vivo. In addition, we show that EGFR inhibition is unique to Kek1 among Kek
      family members and that this function is not ligand or tissue specific. Finally,
      we have identified a unique class of EGFR alleles that specifically disrupt Kek1
      binding and inhibition, but preserve receptor activation. Interestingly, these
      alleles map to domain V of the Drosophila EGFR, a region absent from the
      vertebrate receptors. Together, our results support a model in which the LRRs of
      Kek1 in conjunction with its juxta/transmembrane region direct association and
      inhibition of the Drosophila EGFR through interactions with receptor domain V.

PMID- 15166148
TI  - Toward a comprehensive genetic analysis of male fertility in Drosophila
      melanogaster.
AB  - Drosophila melanogaster is a widely used model organism for genetic dissection of
      developmental processes. To exploit its full potential for studying the genetic
      basis of male fertility, we performed a large-scale screen for male-sterile (ms)
      mutations. From a collection of 12,326 strains carrying ethyl-methanesulfonate
      treated, homozygous viable second or third chromosomes, 2216 ms lines were
      identified, constituting the largest collection of ms mutations described to date
      for any organism. Over 2000 lines were cytologically characterized and, of these,
      81% failed during spermatogenesis while 19% manifested postspermatogenic
      processes. Of the phenotypic categories used to classify the mutants, the largest
      groups were those that showed visible defects in meiotic chromosome segregation
      or cytokinesis and those that failed in sperm individualization. We also
      identified 62 fertile or subfertile lines that showed high levels of chromosome
      loss due to abnormal mitotic or meiotic chromosome transmission in the male germ
      line or due to paternal chromosome loss in the early embryo. We argue that the
      majority of autosomal genes that function in male fertility in Drosophila are
      represented by one or more alleles in the ms collection. Given the conservation
      of molecular mechanisms underlying important cellular processes, analysis of
      these mutations should provide insight into the genetic networks that control
      male fertility in Drosophila and other organisms, including humans.

PMID- 15166149
TI  - A large-scale screen for mutagen-sensitive loci in Drosophila.
AB  - In a screen for new DNA repair mutants, we tested 6275 Drosophila strains bearing
      homozygous mutagenized autosomes (obtained from C. Zuker) for hypersensitivity to
      methyl methanesulfonate (MMS) and nitrogen mustard (HN2). Testing of 2585 second
      chromosome lines resulted in the recovery of 18 mutants, 8 of which were alleles
      of known genes. The remaining 10 second-chromosome mutants were solely sensitive
      to MMS and define 8 new mutagen-sensitive genes (mus212-mus219). Testing of 3690
      third chromosomes led to the identification of 60 third-chromosome mutants, 44 of
      which were alleles of known genes. The remaining 16 mutants define 14 new mutagen
      sensitive genes (mus314-mus327). We have initiated efforts to identify these
      genes at the molecular level and report here the first two identified. The HN2
      sensitive mus322 mutant defines the Drosophila ortholog of the yeast snm1 gene,
      and the MMS- and HN2-sensitive mus301 mutant defines the Drosophila ortholog of
      the human HEL308 gene. We have also identified a second-chromosome mutant,
      mus215(ZIII-2059), that uniformly reduces the frequency of meiotic recombination
      to <3% of that observed in wild type and thus defines a function required for
      both DNA repair and meiotic recombination. At least one allele of each new gene
      identified in this study is available at the Bloomington Stock Center.

PMID- 15166150
TI  - The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved
      in Drosophila and functions in eye development.
AB  - The MITF protein is a member of the MYC family of basic helix-loop-helix leucine
      zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3,
      TFEC, and TFEB proteins. In the mouse, MITF is required for the development of
      several different cell types, including the retinal pigment epithelial (RPE)
      cells of the eye. In Mitf mutant mice, the presumptive RPE cells
      hyperproliferate, abnormally express the retinal transcriptional regulator Pax6,
      and form an ectopic neural retina. Here we report the structure of the Mitf gene
      in Drosophila and demonstrate expression during embryonic development and in the
      eye-antennal imaginal disc. In vitro, transcriptional regulation by Drosophila
      Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6)
      transcription factor. In vivo, targeted expression of wild-type or dominant
      negative Drosophila Mitf results in developmental abnormalities reminiscent of
      Mitf function in mouse eye development. Our results suggest that the Mitf gene is
      the original member of the Mitf-Tfe subfamily of bHLH-Zip proteins and that its
      developmental function is at least partially conserved between vertebrates and
      invertebrates. These findings further support the common origin of the vertebrate
      and invertebrate eyes.

PMID- 15166151
TI  - Whole-genome scan in thelytokous-laying workers of the Cape honeybee (Apis
      mellifera capensis): central fusion, reduced recombination rates and centromere
      mapping using half-tetrad analysis.
AB  - While workers of almost all subspecies of honeybee are able to lay only haploid
      male eggs, Apis mellifera capensis workers are able to produce diploid female
      eggs by thelytokous parthenogenesis. Cytological analyses have shown that during
      parthenogenesis, egg diploidy is restored by fusion of the two central meiotic
      products. This peculiarity of the Cape bee preserves two products of a single
      meiosis in the daughters and can be used to map centromere positions using half
      tetrad analysis. In this study, we use the thelytokous progenies of A. m.
      capensis workers and a sample of individuals from a naturally occurring A. m.
      capensis thelytokous clone to map centromere position for most of the linkage
      groups of the honeybee. We also show that the recombination rate is reduced by
      >10-fold during the meiosis of A. m. capensis workers. This reduction is
      restricted to thelytokous parthenogenesis of capensis workers and is not observed
      in the meiosis of queen within the same subspecies or in arrhenotokous workers of
      another subspecies. The reduced rate of recombination seems to be associated with
      negative crossover interference. These results are discussed in relation to
      evolution of thelytokous parthenogenesis and maintenance of heterozygosity and
      female sex after thelytoky.

PMID- 15166152
TI  - A microsatellite-based linkage map of the honeybee, Apis mellifera L.
AB  - A linkage map for the honeybee (Apis mellifera) was constructed mainly from the
      progeny of two hybrid queens (A. m. ligustica x A. m. mellifera). A total of 541
      loci were mapped; 474 were microsatellite loci; a few were additional bands
      produced during PCRs, one of the two rDNA loci (using ITS), the MDH locus, and
      three sex-linked markers (Q and FB loci and one RAPD band). Twenty-four linkage
      groups were estimated of which 5 were minute (between 7.1 and 22.8 cM) and 19
      were major groups (>76.5 cM). The number of major linkage groups exceeded by
      three the number of chromosomes of the complement (n = 16). The sum of the
      lengths of all linkage groups amounts to 4061 cM to which must be added at least
      320 cM to link groups in excess, making a total of at least 4381 cM. The length
      of the largest linkage group I was 630 cM. The average density of markers was 7.5
      cM and the average resolution was about one marker every 300 kb. For most of the
      large groups, the centromeric region was determined genetically, as described in
      (accompanying article in this issue), using half-tetrad analysis of thelytokous
      parthenogens in which diploid restoration occurs through central fusion. Several
      cases of segregation distortion that appreared to result from deleterious
      recessives were discovered. A low positive interference was also detected.

PMID- 15166153
TI  - Mutational analysis of the Drosophila DNA repair and recombination gene mei-9.
AB  - Drosophila mei-9 is essential for several DNA repair and recombination pathways,
      including nucleotide excision repair (NER), interstrand crosslink repair, and
      meiotic recombination. To better understand the role of MEI-9 in these processes,
      we characterized 10 unique mutant alleles of mei-9. These include a P-element
      insertion that disrupts repair functions but not the meiotic function; three
      nonsense mutations, one of which has nearly wild-type levels of protein; three
      missense mutations, one of which disrupts the meiotic function but not repair
      functions; two small in-frame deletions; and one frameshift.

PMID- 15166154
TI  - The genetics of inviability and male sterility in hybrids between Anopheles
      gambiae and An. arabiensis.
AB  - Male hybrids between Anopheles gambiae and An. arabiensis suffer from hybrid
      sterility, and inviability effects are sometimes present as well. We examined the
      genetic basis of these reproductive barriers between the two species, using 21
      microsatellite markers. Generally, recessive inviability effects were found on
      the X chromosome of gambiae that are incompatible with at least one factor on
      each arabiensis autosome. Inviability is complete when the gambiae and arabiensis
      inviability factors are hemi- or homozygous. Using a QTL mapping approach,
      regions that contribute to male hybrid sterility were also identified. The X
      chromosome has a disproportionately large effect on male hybrid sterility.
      Additionally, several moderate-to-large autosomal QTL were found in both species.
      The effect of these autosomal QTL is contingent upon the presence of an X
      chromosome from the other species. Substantial regions of the autosomes do not
      contribute markedly to male hybrid sterility. Finally, no evidence for epistatic
      interactions between conspecific sterility loci was found.

PMID- 15166155
TI  - Sequences upstream of the homologous cis-elements of the Adh adult enhancer of
      Drosophila are required for maximal levels of Adh gene transcription in adults of
      Scaptodrosophila lebanonensis.
AB  - The evolution of cis-regulatory elements is of particular interest for our
      understanding of the evolution of gene regulation. The Adh gene of Drosophilidae
      shows interspecific differences in tissue-specific expression and transcript
      levels during development. In Scaptodrosophila lebanonensis adults, the level of
      distal transcripts is maximal between the fourth and eighth day after eclosion
      and is around five times higher than that in D. melanogaster Adh(S). To examine
      whether these quantitative differences are regulated by sequences lying upstream
      of the distal promoter, we performed in vitro deletion mutagenesis of the Adh
      gene of S. lebanonensis, followed by P-element-mediated germ-line transformation.
      All constructs included, as a cotransgene, a modified Adh gene of D. melanogaster
      (dAdh) in a fixed position and orientation that acted as a chromosomal position
      control. Using this approach, we have identified a fragment of 1.5 kb in the 5'
      region, 830 bp upstream of the distal start site, which is required to achieve
      maximal levels of distal transcript in S. lebanonensis. The presence of this
      fragment produces a 3.5-fold higher level of distal mRNA (as determined by real
      time quantitative PCR) compared with the D. melanogaster dAdh cotransgene. This
      region contains the degenerated end of a minisatellite sequence expanding farther
      upstream and does not correspond to the Adh adult enhancer (AAE) of D.
      melanogaster. Indeed, the cis-regulatory elements of the AAE have been identified
      by phylogenetic footprinting within the region 830 bp upstream of the distal
      start site of S. lebanonensis. Furthermore, the deletions Delta-830 and Delta
      2358 yield the same pattern of tissue-specific expression, indicating that all
      tissue-specific elements are contained within the region 830 bp upstream of the
      distal start site.

PMID- 15166156
TI  - Genetic mapping of sexual isolation between E and Z pheromone strains of the
      european corn Borer (Ostrinia nubilalis).
AB  - The E and Z pheromone strains of the European corn borer (ECB) provide an
      exceptional model system for examining the genetic basis of sexual isolation.
      Differences at two major genes account for variation in female pheromone
      production and male behavioral response, components of the pheromone
      communication system known to be important for mate recognition and mate choice.
      Strains of ECB are morphologically indistinguishable, and surveys of allozyme and
      DNA sequence variation have revealed significant allele frequency differences at
      only a single sex-linked locus, Tpi. Here we present a detailed genetic linkage
      map of ECB using AFLP and microsatellite markers and map the factors responsible
      for pheromone production (Pher) and male response (Resp). Our map covers 1697 cM
      and identifies all 31 linkage groups in ECB. Both Resp and Tpi map to the Z (sex)
      chromosome, but the distance between these markers (>20 cM) argues against the
      hypothesis that patterns of variation at Tpi are explained by tight linkage to
      this "speciation gene." However, we show, through analysis of marker density,
      that Tpi is located in a region of low recombination and suggest that a second Z
      linked reproductive barrier could be responsible for the origin and/or
      persistence of differentiation at Tpi.

PMID- 15166157
TI  - Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by
      genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila
      melanogaster.
AB  - Adipokinetic hormones (AKHs) are metabolic neuropeptides, mediating mobilization
      of energy substrates from the fat body in many insects. In delving into the roles
      of the Drosophila Akh (dAkh) gene, its developmental expression patterns were
      examined and the physiological functions of the AKH-producing neurons were
      investigated using animals devoid of AKH neurons and ones with ectopically
      expressing dAkh. The dAkh gene is expressed exclusively in the corpora cardiaca
      from late embryos to adult stages. Projections emanating from the AKH neurons
      indicated that AKH has multiple target tissues as follows: the prothoracic gland
      and aorta in the larva and the crop and brain in the adult. Studies using
      transgenic manipulations of the dAkh gene demonstrated that AKH induced both
      hypertrehalosemia and hyperlipemia. Starved wild-type flies displayed prolonged
      hyperactivity prior to death; this novel behavioral pattern could be associated
      with food-searching activities in response to starvation. In contrast, flies
      devoid of AKH neurons not only lacked this type of hyperactivity, but also
      displayed strong resistance to starvation-induced death. From these findings, we
      propose another role for AKH in the regulation of starvation-induced foraging
      behavior.

PMID- 15166158
TI  - An F1 genetic screen for maternal-effect mutations affecting embryonic pattern
      formation in Drosophila melanogaster.
AB  - Large-scale screens for female-sterile mutations have revealed genes required
      maternally for establishment of the body axes in the Drosophila embryo. Although
      it is likely that the majority of components involved in axis formation have been
      identified by this approach, certain genes have escaped detection. This may be
      due to (1) incomplete saturation of the screens for female-sterile mutations and
      (2) genes with essential functions in zygotic development that mutate to
      lethality, precluding their identification as female-sterile mutations. To
      overcome these limitations, we performed a genetic mosaic screen aimed at
      identifying new maternal genes required for early embryonic patterning, including
      zygotically required ones. Using the Flp-FRT technique and a visible germline
      clone marker, we developed a system that allows efficient screening for maternal
      effect phenotypes after only one generation of breeding, rather than after the
      three generations required for classic female-sterile screens. We identified 232
      mutants showing various defects in embryonic pattern or morphogenesis. The
      mutants were ordered into 10 different phenotypic classes. A total of 174 mutants
      were assigned to 86 complementation groups with two alleles on average. Mutations
      in 45 complementation groups represent most previously known maternal genes,
      while 41 complementation groups represent new loci, including several involved in
      dorsoventral, anterior-posterior, and terminal patterning.

PMID- 15166159
TI  - A physically anchored genetic map and linkage to avirulence reveals recombination
      suppression over the proximal region of Hessian fly chromosome A2.
AB  - Resistance in wheat (Triticum aestivum) to the Hessian fly (Mayetiola
      destructor), a major insect pest of wheat, is based on a gene-for-gene
      interaction. Close linkage (3 +/- 2 cM) was discovered between Hessian fly
      avirulence genes vH3 and vH5. Bulked segregant analysis revealed two DNA markers
      (28-178 and 23-201) within 10 cM of these loci and only 3 +/- 2 cM apart.
      However, 28-178 was located in the middle of the short arm of Hessian fly
      chromosome A2 whereas 23-201 was located in the middle of the long arm of
      chromosome A2, suggesting the presence of severe recombination suppression over
      its proximal region. To further test that possibility, an AFLP-based genetic map
      of the Hessian fly genome was constructed. Fluorescence in situ hybridization of
      20 markers on the genetic map to the polytene chromosomes of the Hessian fly
      indicated good correspondence between the linkage groups and the four Hessian fly
      chromosomes. The physically anchored genetic map is the first of any gall midge
      species. The proximal region of mitotic chromosome A2 makes up 30% of its length
      but corresponded to <3% of the chromosome A2 genetic map.

PMID- 15166160
TI  - An invertebrate histocompatibility complex.
AB  - We have developed defined genetic lines of the hydroid Hydractinia
      symbiolongicarpus and confirmed earlier results showing that allorecognition is
      controlled by a single chromosomal region within these lines. In a large
      backcross population, we detected recombinants that display a fusibility
      phenotype distinct from typical fusion and rejection. We show that this
      transitory fusion phenotype segregates in a fashion expected of a single
      Mendelian trait, establishing that the chromosomal interval contains at least two
      genes that interact to determine fusibility. Using bulked segregant analysis, we
      have identified amplified fragment length polymorphisms (AFLP) cosegregating with
      fusibility, used these markers to independently confirm linkage of the two loci,
      and constructed a 3.4-cM map of an invertebrate histocompatibility complex.

PMID- 15166161
TI  - Evolutionary strata on the chicken Z chromosome: implications for sex chromosome
      evolution.
AB  - The human X chromosome exhibits four "evolutionary strata," interpreted to
      represent distinct steps in the process whereby recombination became arrested
      between the proto X and proto Y. To test if this is a general feature of sex
      chromosome evolution, we studied the Z-W sex chromosomes of birds, which have
      female rather than male heterogamety and evolved from a different autosome pair
      than the mammalian X and Y. Here we analyze all five known gametologous Z-W gene
      pairs to investigate the "strata" hypothesis in birds. Comparisons of the rates
      of synonymous substitution and intronic divergence between Z and W gametologs
      reveal the presence of at least two evolutionary strata spread over the p and q
      arms of the chicken Z chromosome. A phylogenetic analysis of intronic sequence
      data from different avian lineages indicates that Z-W recombination ceased in the
      oldest stratum (on Zq; CHD1Z, HINTZ, and SPINZ) 102-170 million years ago (MYA),
      before the split of the Neoaves and Eoaves. However, recombination continued in
      the second stratum (on Zp; UBAP2Z and ATP5A1Z) until after the divergence of
      extant avian orders, with Z and W diverging 58-85 MYA. Our data suggest that
      progressive and stepwise cessation of recombination is a general feature behind
      sex chromosome evolution.

PMID- 15166163
TI  - Insights into recombination from patterns of linkage disequilibrium in humans.
AB  - An ability to predict levels of linkage disequilibrium (LD) between linked
      markers would facilitate the design of association studies and help to
      distinguish between evolutionary models. Unfortunately, levels of LD depend
      crucially on the rate of recombination, a parameter that is difficult to measure.
      In humans, rates of genetic exchange between markers megabases apart can be
      estimated from a comparison of genetic and physical maps; these large-scale
      estimates can then be interpolated to predict LD at smaller ("local") scales.
      However, if there is extensive small-scale heterogeneity, as has been recently
      proposed, local rates of recombination could differ substantially from those
      averaged over much larger distances. We test this hypothesis by estimating local
      recombination rates indirectly from patterns of LD in 84 genomic regions surveyed
      by the SeattleSNPs project in a sample of individuals of European descent and of
      African-Americans. We find that LD-based estimates are significantly positively
      correlated with map-based estimates. This implies that large-scale, average rates
      are informative about local rates of recombination. Conversely, although LD-based
      estimates are based on a number of simplifying assumptions, it appears that they
      capture considerable information about the underlying recombination rate or at
      least about the ordering of regions by recombination rate. Using LD-based
      estimators, we also find evidence for homologous gene conversion in patterns of
      polymorphism. However, as we demonstrate by simulation, inferences about gene
      conversion are unreliable, even with extensive data from homogeneous regions of
      the genome, and are confounded by genotyping error.

PMID- 15166162
TI  - Reduced variation on the chicken Z chromosome.
AB  - Understanding the population genetic factors that shape genome variability is
      pivotal to the design and interpretation of studies using large-scale
      polymorphism data. We analyzed patterns of polymorphism and divergence at Z
      linked and autosomal loci in the domestic chicken (Gallus gallus) to study the
      influence of mutation, effective population size, selection, and demography on
      levels of genetic diversity. A total of 14 autosomal introns (8316 bp) and 13 Z
      linked introns (6856 bp) were sequenced in 50 chicken chromosomes from 10 highly
      divergent breeds. Genetic variation was significantly lower at Z-linked than at
      autosomal loci, with one segregating site every 39 bp at autosomal loci (theta(W)
      = 5.8 +/- 0.8 x 10(-3)) and one every 156 bp on the Z chromosome (theta(W) = 1.4
      +/- 0.4 x 10(-3)). This difference may in part be due to a low male effective
      population size arising from skewed reproductive success among males, evident
      both in the wild ancestor-the red jungle fowl-and in poultry breeding. However,
      this effect cannot entirely explain the observed three- to fourfold reduction in
      Z chromosome diversity. Selection, in particular selective sweeps, may therefore
      have had an impact on reducing variation on the Z chromosome, a hypothesis
      supported by the observation of heterogeneity in diversity levels among loci on
      the Z chromosome and the lower recombination rate on Z than on autosomes.
      Selection on sex-linked genes may be particularly important in organisms with
      female heterogamety since the heritability of sex-linked sexually antagonistic
      alleles advantageous to males is improved when fathers pass a Z chromosome to
      their sons.

PMID- 15166164
TI  - Characterization of epistasis influencing complex spontaneous obesity in the BSB
      model.
AB  - There is growing awareness that complex interactions among multiple genes and
      environmental factors play an important role in controlling obesity traits. The
      BSB mouse, which is produced by the backcross of (lean C57BL/6J x lean Mus
      spretus) x C57BL/6J, provides an excellent model of epistatic obesity. To
      evaluate potential epistatic interactions among six chromosomal regions
      previously determined to influence obesity phenotypes, we performed novel
      Bayesian analyses on the basis of both epistatic and nonepistatic models for four
      obesity traits: percentage of body fat, adiposity index, total fat mass, and body
      weight, and also for plasma total cholesterol. The epistatic analysis detected at
      least one more QTL than the nonepistatic analysis did for all obesity traits.
      These obesity traits were variously influenced by QTL on chromosomes 2, 7, 12,
      15, and 16. Interaction between genes on chromosomes 2 and 12 was present for all
      obesity traits, accounting for 3-4.8% of the phenotypic variation. Chromosome 12
      was found to have weak main effects on all obesity traits. Several different
      epistatic interactions were also detected for percentage of body fat, adiposity
      index, and total fat mass. Chromosomes 6 and 12 have not only main effects but
      also strong epistatic effects on plasma total cholesterol. Our results emphasize
      the importance of modeling epistasis for discovery of obesity genes.

PMID- 15166165
TI  - The epigenetic stability of the locus control region-deficient IgH locus in mouse
      hybridoma cells is a clonally varying, heritable feature.
AB  - Cis-acting elements such as enhancers and locus control regions (LCRs) prevent
      silencing of gene expression. We have shown previously that targeted deletion of
      an LCR in the immunoglobulin heavy-chain (IgH) locus creates conditions in which
      the immunoglobulin micro heavy chain gene can exist in either of two
      epigenetically inherited states, one in which micro expression is positive and
      one in which micro expression is negative, and that the positive and negative
      states are maintained by a cis-acting mechanism. As described here, the stability
      of these states, i.e., the propensity of a cell to switch from one state to the
      other, varied among subclones and was an inherited, clonal feature. A similar
      variation in stability was seen for IgH loci that both lacked and retained the
      matrix attachment regions associated with the LCR. Our analysis of cell hybrids
      formed by fusing cells in which the micro expression had different stabilities
      indicated that stability was also determined by a cis-acting feature of the IgH
      locus. Our results thus show that a single-copy gene in the same chromosomal
      location and in the presence of the same transcription factors can exist in many
      different states of expression.

PMID- 15166166
TI  - Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X
      chromosome in humans.
AB  - The centromeric region of the X chromosome in humans experiences low rates of
      recombination over a considerable physical distance. In such a region, the
      effects of selection may extend to linked sites that are far away. To investigate
      the effects of this recombinational environment on patterns of nucleotide
      variability, we sequenced 4581 bp at Msn and 4697 bp at Alas2, two genes situated
      on either side of the X chromosome centromere, in a worldwide sample of 41 men,
      as well as in one common chimpanzee and one orangutan. To investigate patterns of
      linkage disequilibrium (LD) across the centromere, we also genotyped several
      informative sites from each gene in 120 men from sub-Saharan Africa. By studying
      X-linked loci in males, we were able to recover haplotypes and study long-range
      patterns of LD directly. Overall patterns of variability were remarkably similar
      at these two loci. Both loci exhibited (i) very low levels of nucleotide
      diversity (among the lowest seen in the human genome); (ii) a strong skew in the
      distribution of allele frequencies, with an excess of both very-low and very-high
      frequency derived alleles in non-African populations; (iii) much less variation
      in the non-African than in the African samples; (iv) very high levels of
      population differentiation; and (v) complete LD among all sites within loci. We
      also observed significant LD between Msn and Alas2 in Africa, despite the fact
      that they are separated by approximately 10 Mb. These observations are difficult
      to reconcile with a simple demographic model but may be consistent with positive
      and/or purifying selection acting on loci within this large region of low
      recombination.

PMID- 15166167
TI  - Genetics of barley hooded suppression.
AB  - The molecular basis of the barley dominant Hooded (K) mutant is a duplication of
      305 bp in intron IV of the homeobox gene Bkn3. A chemical mutagenesis screen was
      carried out to identify genetical factors that participate in Bkn3 intron
      mediated gene regulation. Plants from recurrently mutagenized KK seeds were
      examined for the suppression of the hooded awn phenotype induced by the K allele
      and, in total, 41 suK (suppressor of K) recessive mutants were identified.
      Complementation tests established the existence of five suK loci, and alleles
      suKB-4, suKC-33, suKD-25, suKE-74, and suKF-76 were studied in detail. All K
      suppressed mutants showed a short-awn phenotype. The suK loci have been mapped by
      bulked segregant analysis nested in a standard mapping procedure based on AFLP
      markers. K suppressor loci suKB, B, E, and F all map in a short interval of
      chromosome 7H, while the locus suKD is assigned to chromosome 5H. A
      complementation test between the four suK mutants mapping on chromosome 7H and
      the short-awn mutant lks2, located nearby, excluded the allelism between suK loci
      and lks2. The last experiment made clear that the short-awn phenotype of suK
      mutants is due to a specific dominant function of the K allele, a function that
      is independent from the control on hood formation. The suK loci are discussed as
      candidate participants in the regulation of Bkn3 expression.

PMID- 15166168
TI  - Comparative mapping and rapid karyotypic evolution in the genus helianthus.
AB  - Comparative genetic linkage maps provide a powerful tool for the study of
      karyotypic evolution. We constructed a joint SSR/RAPD genetic linkage map of the
      Helianthus petiolaris genome and used it, along with an integrated SSR genetic
      linkage map derived from four independent H. annuus mapping populations, to
      examine the evolution of genome structure between these two annual sunflower
      species. The results of this work indicate the presence of 27 colinear segments
      resulting from a minimum of eight translocations and three inversions. These 11
      rearrangements are more than previously suspected on the basis of either
      cytological or genetic map-based analyses. Taken together, these rearrangements
      required a minimum of 20 chromosomal breakages/fusions. On the basis of estimates
      of the time since divergence of these two species (750,000-1,000,000 years), this
      translates into an estimated rate of 5.5-7.3 chromosomal rearrangements per
      million years of evolution, the highest rate reported for any taxonomic group to
      date.

PMID- 15166169
TI  - Genetic variation at the tomato Cf-4/Cf-9 locus induced by EMS mutagenesis and
      intralocus recombination.
AB  - The interaction between tomato (Lycopersicon esculentum) and the leaf mold
      pathogen Cladosporium fulvum is an excellent model for investigating disease
      resistance gene evolution. The interaction is controlled in a gene-for-gene
      manner by Cf genes that encode type I transmembrane extracellular leucine-rich
      repeat glycoproteins that recognize their cognate fungal avirulence (Avr)
      proteins. Cf-4 from L. hirsutum and Cf-9 from L. pimpinellifolium are located at
      the same locus on the short arm of tomato chromosome 1 in an array of five
      paralogs. Molecular analysis has shown that one mechanism for generating sequence
      variation in Cf genes is intragenic sequence exchange through unequal crossing
      over or gene conversion. To investigate this we used a facile genetic selection
      to identify novel haplotypes in the progeny of Cf-4/Cf-9 trans-heterozygotes that
      lacked Cf-4 and Cf-9. This selection is based on the ability of Avr4 and Avr9 to
      induce Cf-4- or Cf-9-dependent seedling death. The crossovers were localized to
      the same intergenic region defining a recombination hotspot in this cross. As
      part of a structure-function analysis of Cf-9 and Cf-4, nine EMS-induced mutant
      alleles have been characterized. Most mutations result in single-amino-acid
      substitutions in their C terminus at residues that are conserved in other Cf
      proteins.

PMID- 15166171
TI  - Quantitative trait locus mapping based on resampling in a vast maize testcross
      experiment and its relevance to quantitative genetics for complex traits.
AB  - From simulation studies it is known that the allocation of experimental resources
      has a crucial effect on power of QTL detection as well as on accuracy and
      precision of QTL estimates. In this study, we used a very large experimental data
      set composed of 976 F(5) maize testcross progenies evaluated in 19 environments
      and cross-validation to assess the effect of sample size (N), number of test
      environments (E), and significance threshold on the number of detected QTL, the
      proportion of the genotypic variance explained by them, and the corresponding
      bias of estimates for grain yield, grain moisture, and plant height. In addition,
      we used computer simulations to compare the usefulness of two cross-validation
      schemes for obtaining unbiased estimates of QTL effects. The maximum, validated
      genotypic variance explained by QTL in this study was 52.3% for grain moisture
      despite the large number of detected QTL, thus confirming the infinitesimal model
      of quantitative genetics. In both simulated and experimental data, the effect of
      sample size on power of QTL detection as well as on accuracy and precision of QTL
      estimates was large. The number of detected QTL and the proportion of genotypic
      variance explained by QTL generally increased more with increasing N than with
      increasing E. The average bias of QTL estimates and its range were reduced by
      increasing N and E. Cross-validation performed well with respect to yielding
      asymptotically unbiased estimates of the genotypic variance explained by QTL. On
      the basis of our findings, recommendations for planning of QTL mapping
      experiments and allocation of experimental resources are given.

PMID- 15166172
TI  - Frequency-dependent selection with dominance: a window onto the behavior of the
      mean fitness.
AB  - Selection in which fitnesses vary with the changing genetic composition of the
      population may facilitate the maintenance of genetic diversity in a wide range of
      organisms. Here, a detailed theoretical investigation is made of a frequency
      dependent selection model, in which fitnesses are based on pairwise interactions
      between the two phenotypes at a diploid, diallelic, autosomal locus with complete
      dominance. The allele frequency dynamics are fully delimited analytically, along
      with all possible shapes of the mean fitness function in terms of where it
      increases or decreases as a function of the current allele frequency in the
      population. These results in turn allow possibly the first complete
      characterization of the dynamical behavior by the mean fitness through time under
      frequency-dependent selection. Here the mean fitness (i) monotonically increases,
      (ii) monotonically decreases, (iii) initially increases and then decreases, or
      (iv) initially decreases and then increases as equilibrium is approached. We
      analytically derive the exact initial and fitness conditions that produce each
      dynamic and how often each arises. Computer simulations with random initial
      conditions and fitnesses reveal that the potential decline in mean fitness is not
      negligible; on average a net decrease occurs 20% of the time and reduces the mean
      fitness by >17%.

PMID- 15166173
TI  - Mutators in space: the dynamics of high-mutability clones in a two-patch model.
AB  - Clones of bacteria possessing high-mutability rates (or mutators) are being
      observed in an increasing number of species. In a constant environment most
      mutations are deleterious, and hence the spontaneous mutation rate is generally
      low. However, mutators may play an important role in the adaptation of organisms
      to changing environments. To date, theoretical work has focused on temporal
      variability in the environment, implicitly assuming that environmental conditions
      are constant through space. Here, we develop a two-patch model to investigate how
      spatiotemporal environmental variability and dispersal might influence mutator
      dynamics. Environmental conditions in each patch fluctuate between two states;
      the rate of fluctuation varies in each patch at differing phase angles. We find
      that at low and intermediate rates of fluctuation, an increase in dispersal
      results in a decrease in the density of mutators. However, at high rates of
      environmental change, dispersal causes an increase in mutator density. For all
      frequencies of environmental fluctuation these trends are enhanced as the phase
      angle approaches 180 degrees. We argue that future work, both empirical and
      theoretical, is needed to improve our understanding of how spatiotemporal
      variability impacts on mutator densities and dynamics.

PMID- 15166175
TI  - Statistical framework for phylogenomic analysis of gene family expression
      profiles.
AB  - Microarray technology has produced massive expression data that are invaluable
      for investigating the genome-wide evolutionary pattern of gene expression. To
      this end, phylogenetic expression analysis is highly desirable. On the basis of
      the Brownian process, we developed a statistical framework (called the E(0)
      model), assuming the independent expression of evolution between lineages.
      Several evolutionary mechanisms are integrated to characterize the pattern of
      expression diversity after gene duplications, including gradual drift and
      dramatic shift (punctuated equilibrium). When the phylogeny of a gene family is
      given, we show that the likelihood function follows a multivariate normal
      distribution; the variance-covariance matrix is determined by the phylogenetic
      topology and evolutionary parameters. Maximum-likelihood methods for multiple
      microarray experiments are developed, and likelihood-ratio tests are designed for
      testing the evolutionary pattern of gene expression. To reconstruct the
      evolutionary trace of expression diversity after gene (or genome) duplications,
      we developed a Bayesian-based method and use the posterior mean as predictors.
      Potential applications in evolutionary genomics are discussed.

PMID- 15166174
TI  - Stochastic gene expression in fluctuating environments.
AB  - Stochastic mechanisms can cause a group of isogenic bacteria, each subject to
      identical environmental conditions, to nevertheless exhibit diverse patterns of
      gene expression. The resulting phenotypic subpopulations will typically have
      distinct growth rates. This behavior has been observed in several contexts,
      including sugar metabolism and pili phase variation. Under fixed environmental
      conditions, the net growth rate of the population is maximized when all cells are
      of the fastest growing phenotype, so it is unclear what fitness advantage is
      conferred by population heterogeneity. However, unlike ideal laboratory
      conditions, natural environments tend to fluctuate, either periodically or
      randomly. Here we use a stochastic population model to show that, during growth
      in such fluctuating environments, a dynamically heterogenous bacterial population
      can sometimes achieve a higher net growth rate than a homogenous one. By using
      stochastic mechanisms to sample several distinct phenotypes, the bacteria are
      able to anticipate and take advantage of sudden changes in their environment.
      However, this heterogeneity is beneficial only if the bacterial response rate is
      sufficiently low. Our results could be useful in the design of artificial
      evolution experiments and in the optimization of fermentation processes.

PMID- 15166176
TI  - Natural selection affects frequencies of AG and GT dinucleotides at the 5' and 3'
      ends of exons.
AB  - GT and AG, located at the 5' and 3' ends of introns, are important for correct
      splicing. It is anticipated that natural selection decreases frequency of AG and
      GT near the 5' and 3' ends of exons, preventing appearance of cryptic splicing
      sites. The data presented in this article support the expectation.

PMID- 15166177
TI  - Comparing analysis methods for mutation-accumulation data.

PMID- 15166170
TI  - Comparative population genetics of the panicoid grasses: sequence polymorphism,
      linkage disequilibrium and selection in a diverse sample of sorghum bicolor.
AB  - Levels of genetic variation and linkage disequilibrium (LD) are critical factors
      in association mapping methods as well as in identification of loci that have
      been targets of selection. Maize, an outcrosser, has a high level of sequence
      variation and a limited extent of LD. Sorghum, a closely related but largely self
      pollinating panicoid grass, is expected to have higher levels of LD. As a first
      step in estimation of population genetic parameters in sorghum, we surveyed 27
      diverse S. bicolor accessions for sequence variation at a total of 29,186 bp in
      95 short regions derived from genetically mapped RFLPs located throughout the
      genome. Consistent with its higher level of inbreeding, the extent of LD is at
      least severalfold greater in sorghum than in maize. Total sequence variation in
      sorghum is about fourfold lower than that in maize, while synonymous variation is
      fivefold lower, suggesting a smaller effective population size in sorghum.
      Because we surveyed a species-wide sample, the mating system, which primarily
      affects population-level diversity, may not be primarily responsible for this
      difference. Comparisons of polymorphism and divergence suggest that both
      directional and diversifying selection have played important roles in shaping
      variation in the sorghum genome.

PMID- 15166179
TI  - Gene therapy and heme oxygenase coming of age.

PMID- 15166178
TI  - Statin therapy: having the good without the bad.

PMID- 15166181
TI  - Heme oxygenase-1 gene expression modulates angiotensin II-induced increase in
      blood pressure.
AB  - The heme-heme oxygenase (HO) system has been implicated in the regulation of
      vascular reactivity and blood pressure. This study examines the notion that
      overexpression of HO decreases pressor responsiveness to angiotensin II (Ang II).
      Five-day-old Sprague-Dawley rats received an intraleft ventricular injection of
      approximately 5x10(9) cfu/mL of retroviruses containing human HO-1 sense (LSN-HHO
      1), rat HO-1 antisense (LSN-RHO-1-AS), or control retrovirus (LXSN). Three months
      later, rats were instrumented with femoral arterial and venous catheters for mean
      arterial pressure (MAP) determination and Ang II administration, respectively.
      Rats injected with LSN-HHO-1, but not with LXSN, expressed human HO-1 mRNA and
      protein in several tissues. BP increased with administration of Ang II in rats
      expressing and not expressing human HO-1. However, the Ang II-induced pressor
      response (mm Hg) in LSN-HHO-1 rats (16+/-3, 27+/-3, and 38+/-3 at 0.5, 2, and 10
      ng) was surpassed (P<0.05) in LXSN rats (23+/-1, 37+/-2, and 52+/-2 at 0.5, 2,
      and 10 ng). Importantly, treating LSN-HHO-1 rats with the HO inhibitor tin
      mesoporphyrin (SnMP) enhanced (P<0.05) the Ang II-induced pressor response to a
      level not different from that observed in LXSN rats. Rats injected with LSN-RHO-1
      AS showed a decrease in renal HO-1 protein expression and HO activity relative to
      control LXSN rats. Administration of Ang II (0.1 to 2 ng) caused small (4 to 5 mm
      Hg) but significant increases in MAP in rats injected with LSN-RHO-1-AS (P<0.05)
      compared with rats injected with LXSN. These data demonstrate that overexpression
      of HO-1 brings about a reduction in pressor responsiveness to Ang II, which is
      most likely due to increased generation of an HO-1 product, presumably CO, with
      the ability to inhibit vascular reactivity to constrictor stimuli.

PMID- 15166180
TI  - Statins augment collateral growth in response to ischemia but they do not promote
      cancer and atherosclerosis.
AB  - 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are
      widely prescribed to lower cholesterol. Recent reports suggest that statins may
      promote angiogenesis in ischemic tissues. It remains to be elucidated whether
      statins potentially enhance unfavorable angiogenesis associated with tumor and
      atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by
      resecting the right femoral artery and subsequently inoculated cancer cells in
      the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind
      limb as determined by laser Doppler imaging, whereas tumor growth was
      significantly retarded. Cerivastatin did not affect capillary density in tumors.
      Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion
      progression in apolipoprotein E-deficient mice, whereas they augmented blood flow
      recovery and capillary formation in ischemic hind limb. Low-dose statins were
      more effective than high-dose statins in both augmentation of collateral flow
      recovery and inhibition of atherosclerosis. These results suggest that statins
      may not promote the development of cancer and atherosclerosis at the doses that
      augment collateral flow growth in ischemic tissues.

PMID- 15166182
TI  - Prevention of cardiac hypertrophy by angiotensin II type-2 receptor gene
      transfer.
AB  - The role of the angiotensin II type-2 receptor (AT2R) in cardiac hypertrophy
      remains elusive despite its demonstrated involvement in cardiovascular
      development. We have previously shown that a lentiviral vector gene delivery
      system is able to transduce cardiac tissue with high efficiency in vivo. Using
      such an approach, our objectives in the present study were 2-fold: (1) to
      overexpress the AT2R in cardiac tissue after completion of natural embryonic
      development of the heart and (2) to determine the effects of this overexpression
      on cardiac hypertrophy and basal blood pressure (BP). A lentiviral vector
      encoding the AT2R (lenti-AT2R) was administered (1.5x10(8) transducing units)
      into the left ventricular space of 5-day-old spontaneously hypertensive rats
      (SHRs). AT2R transgene expression increased in these animals and persisted for 30
      weeks. In contrast, the expression of the angiotensin II type-1 receptor remained
      unchanged following lenti-AT2R treatment. At 21 weeks following gene
      transduction, the lenti-AT2R-treated SHRs exhibited decreased left ventricular
      wall thickness compared with control animals. In contrast, basal BP did not
      differ between the two SHR groups. Finally, heart weight to body weight ratios
      indicated a significant decrease in lenti-AT2R-treated SHRs compared with SHR
      controls. Our data indicate that AT2R overexpression attenuates cardiac
      hypertrophy in the SHR. This beneficial outcome was observed despite the
      existence of elevated BP.

PMID- 15166187
TI  - Epigenetic epidemiology.

PMID- 15166183
TI  - Neuroendocrine transcriptome in genetic hypertension: multiple changes in diverse
      adrenal physiological systems.
AB  - The genetic basis of hypertension in the genetically/hereditary hypertensive
      (BPH/2) mouse strain is incompletely understood, although a recent genome scan
      uncovered evidence for several susceptibility loci. To probe the neuroendocrine
      transcriptome in this disease model, 12 488 probe set microarray experiments were
      performed on mRNA transcripts from adrenal glands of juvenile (prehypertensive)
      and adult BPH/2 (hypertensive), as well as the genetically/hereditary low-blood
      pressure (BPL/1), strains at both time points. To determine the impact of strain
      (BPH/2 versus BPL/1), age (juvenile versus adult), and the interaction of strain
      and age on gene expression levels, we performed standard 2-factor ANOVA and
      computed a concordance coefficient to assess the reproducibility of gene
      expression measurements among replicates. Of genes with significant (P<0.05)
      differential expression, 2647 showed strain differences, 982 showed age
      differences, and 757 exhibited strain-by-age interaction. Fold-changes in gene
      expression assayed by microarray were confirmed in a subset by real-time
      polymerase chain reaction (R=0.739, P=0.0094). We used a systems biology approach
      to evaluate alterations in contributing biochemical pathways and we statistically
      quantified these global pathway disturbances using the Kolmogorov-Smirnov
      goodness-of-fit test. We found widespread, indeed global, alterations in patterns
      of gene expression in diverse systems of BPH/2: in sympathochromaffin transcripts
      suggesting increased sympathetic stimulation; in vasoconstrictor/vasodilator
      systems; global reductions in carbohydrate intermediary metabolism; and increases
      in oxidative stress, with changes in oxygen radical forming and disposition
      enzymes. These analyses highlight widespread derangements in diverse
      physiological pathways, providing multiple avenues for further investigation into
      the pathogenesis of genetic hypertension.

PMID- 15166188
TI  - Methodological and quality issues in epidemiological studies of acute lower
      respiratory infections in children in developing countries.
AB  - Acute respiratory infections are the most important single cause of global burden
      of disease in young children globally and a major cause of child mortality. A
      recent review of studies reporting the incidence of acute lower respiratory
      infections (ALRI) in young children in the developing world was carried out by
      the WHO Child Health Epidemiology Reference Group in order to inform global
      burden of disease estimates. The review highlighted the low number of community
      based longitudinal studies of ALRI incidence in young children which met minimum
      quality criteria. It underscored the need to give attention to issues of study
      design and the reporting of a basic minimum dataset which describes circumstances
      under which the studies were being conducted and the key design features of the
      study which may influence the ALRI estimate. This paper aims to provide
      methodological guidelines for the design, conduct, and reporting of
      epidemiological studies of ALRI in under-5s in developing countries. It discusses
      determinants of study quality related to both study design and statistical
      analysis and also issues requiring further research. It is hoped that these
      guidelines will stimulate further work in this field and encourage the
      publication of reports which contain sufficient data to permit a meaningful meta
      analysis of the data, thus forming the basis of more reliable future estimates of
      global burden of ALRI.

PMID- 15166190
TI  - Thyroid cancer incidence trends in Belarus: examining the impact of Chernobyl.
AB  - BACKGROUND: While prior studies of thyroid cancer incidence within Belarus have
      increased since the 1986 Chernobyl reactor accident, the magnitude of increase is
      not well quantified. METHODS: Using Belarussian national cancer registry data,
      trends in average annual age-adjusted thyroid cancer incidence rates were
      examined by calendar year and gender. Incidence rates were also examined across
      specified time intervals, for specific age groups at diagnosis, and in 'higher
      exposure' regions compared with 'lower exposure' areas. RESULTS: Age-adjusted
      thyroid cancer incidence rates (adjusted to the WHO 2000 world population) have
      increased between 1970 and 2001 from 0.4 per 100 000 to 3.5 per 100 000 among
      males (+775%) and from 0.8 per 100 000 to 16.2 per 100 000 among females
      (+1925%). The relative increase among males (+1020%) and females (+3286%) in
      'high exposure' areas exceeded increases among males (+571%) and females (+250%)
      in 'lower exposure' areas of Belarus. Dramatic increases in thyroid cancer
      incidence rate ratios were noted among both males and females and in all age
      groups. The highest incidence rate ratios were observed among people from 'higher
      exposure' areas ages 0-14 yr at time of diagnosis. CONCLUSIONS: Marked increases
      in the incidence of thyroid cancer have occurred over a relatively limited period
      of observation in all areas of the Republic of Belarus and among all age
      categories. The greatest increases have occurred among children, suggesting that
      a high prevalence of pre-existing iodine deficiency in combination with unique
      susceptibility among younger people might have contributed to potential
      carcinogenic exposures to the thyroid.

PMID- 15166191
TI  - Commentary: hormone replacement therapy and coronary heart disease: four lessons.

PMID- 15166192
TI  - Commentary: hormones and heart disease: do trials and observational studies
      address different questions?

PMID- 15166193
TI  - Ethnic inequalities in age- and cause-specific mortality in The Netherlands.
AB  - BACKGROUND: By describing ethnic differences in age- and cause-specific mortality
      in The Netherlands we aim to identify factors that determine whether ethnic
      minority groups have higher or lower mortality than the native population of the
      host country. METHODS: We used data for 1995-2000 from the municipal population
      registers and cause of death registry. All inhabitants of The Netherlands were
      included in the study. The mortality of people who themselves or whose parent(s)
      were born in Turkey, Morocco, Surinam, or the Dutch Antilles/Aruba was compared
      with that of the native Dutch population. Mortality differences were estimated by
      Poisson regression analyses and by directly standardized mortality rates.
      RESULTS: Compared with native Dutch men, mortality was higher among Turkish
      (relative risk [RR] = 1.21, 95% CI: 1.16, 1.26), Surinamese (RR = 1.24, 95% CI:
      1.19, 1.29), and Antillean/Aruban (RR = 1.25, 95% CI: 1.15, 1.36) males, and
      lower among Moroccan males (RR = 0.85, 95% CI: 0.81, 0.90). Among females,
      inequalities in mortality were small. In general, mortality differences were
      influenced by socio-economic and marital status. Most minority groups had a high
      mortality at young ages and low mortality at older ages, a high mortality from
      ill-defined conditions (which is related to mortality abroad) and external
      causes, and a low mortality from neoplasms. Cardiovascular disease mortality was
      low among Moroccan males (RR = 0.51, 95% CI: 0.44, 0.59) and high among
      Surinamese males (RR = 1.13, 95% CI: 1.05, 1.21) and females (RR = 1.14, 95% CI:
      1.06, 1.23). Homicide mortality was elevated in all groups. CONCLUSION: Socio
      economic factors and marital status were important determinants of ethnic
      inequalities in mortality in The Netherlands. Mortality from cardiovascular
      diseases, homicide, and mortality abroad were of particular importance for
      shifting the balance from high towards low all-cause mortality.

PMID- 15166194
TI  - Fetal growth, maternal prenatal smoking, and risk of invasive meningococcal
      disease: a nationwide case-control study.
AB  - BACKGROUND: The prenatal period may be important for susceptibility to
      infections. We evaluated whether low birthweight, prematurity, and prenatal
      maternal smoking were associated with increased risk of invasive meningococcal
      disease. METHODS: We linked the Danish nationwide National Registry of Patients,
      the Birth Registry, and social registries to obtain data on fetal growth and
      social factors on 1921 cases of meningococcal disease hospitalized between 1
      January, 1980 and 31 December, 1999 (median age 31 months, interquartiles 13-65
      months) and 37 451 population controls. The impact of maternal smoking was
      examined in a subsample of 462 cases and 9240 controls born after 1990, when data
      on smoking became available in the Birth Registry. RESULTS: The adjusted odds
      ratios (OR) of meningococcal disease associated with low birthweight (<2500 g)
      varied between 1.6 (95% CI: 1.1, 2.3) in infants <12 months to 1.5 (95% CI: 1.0,
      2.3) in children >60 months of age at hospitalization for meningococcal disease.
      Premature children had an increased risk of meningococcal disease during the
      first year of life only (adjusted OR = 1.3, 95% CI: 1.1, 1.9). The effect of low
      birthweight was very similar among mature and premature children. The adjusted OR
      for maternal smoking was 1.8 (95% CI: 1.4, 2.2). CONCLUSIONS: Low birthweight is
      associated with an increased risk of meningococcal disease throughout childhood,
      while an effect of prematurity persists only for 12 months. Maternal prenatal
      smoking was associated with the risk of meningococcal disease.

PMID- 15166195
TI  - Physical activity and stroke. A meta-analysis of observational data.
AB  - BACKGROUND: Based on studies published so far, the protective effect of physical
      activity on stroke remains controversial. Specifically, there is a lack of
      insight into the sources of heterogeneity between studies. METHODS: Meta-analysis
      of observational studies was used to quantify the relationship between physical
      activity and stroke and to explore sources of heterogeneity. In total, 31
      relevant publications were included. Risk estimates and study characteristics
      were extracted from original studies and converted to a standard format for use
      in a central database. RESULTS: Moderately intense physical activity compared
      with inactivity, showed a protective effect on total stroke for both occupational
      (RR = 0.64, 95% CI: 0.48-0.87) and leisure time physical activity (RR = 0.85, 95%
      CI: 0.78-0.93). High level occupational physical activity protected against
      ischaemic stroke compared with both moderate (RR = 0.77, 95% CI: 0.60-0.98) and
      inactive occupational levels (RR = 0.57, 95% CI: 0.43-0.77). High level compared
      with low level leisure time physical activity protected against total stroke (RR
      = 0.78, 95% CI: 0.71-0.85), haemorrhagic stroke (RR = 0.74, 95% CI: 0.57-0.96) as
      well as ischaemic stroke (RR = 0.79, 95% CI: 0.69-0.91). Studies conducted in
      Europe showed a stronger protective effect (RR = 0.47, 95% CI: 0.33-0.66) than
      studies conducted in the US (RR = 0.82, 95% CI: 0.75-0.90). CONCLUSIONS: Lack of
      physical activity is a modifiable risk factor for both total stroke and stroke
      subtypes. Moderately intense physical activity is sufficient to achieve risk
      reduction.

PMID- 15166196
TI  - Commentary: Maternal nutrition, body proportions at birth, and adult chronic
      disease.

PMID- 15166197
TI  - Commentary: Beyond urban-rural comparisons: towards a life course approach to
      understanding health effects of urbanization.

PMID- 15166198
TI  - Commentary: Fetal origins of social situations? Medicalization of social life?

PMID- 15166199
TI  - Does conflict between home and work explain the effect of multiple roles on
      mental health? A comparative study of Finland, Japan, and the UK.
AB  - BACKGROUND: Although there have been a number of studies on the effects of
      multiple roles on health and how a combination of work and family roles may be
      either advantageous (role enhancement) or disadvantageous (role strain) for
      health, there has been relatively little investigation on the psychosocial
      content of such roles. Work-to-family conflict and family-to-work conflict could
      arise from inability to combine multiple roles and result in stress and ill
      health. The question of whether both types of conflict mediate between the
      association of multiple roles with health has not been analysed before. This
      paper sets out to investigate whether: (1) work-to-family conflict or family-to
      work conflict contributes towards explaining the association of multiple roles
      with mental health; (2) the effect of work-to-family conflict and family-to-work
      conflict on mental health varies by gender; (3) the effect of work-to-family and
      family-to-work conflict on mental health vary between countries with different
      welfare state arrangements and social norms. METHODS: Cross-sectional data of
      economically active male and female public sector employees aged 35-60 in London
      (UK), Helsinki (Finland), and the West Coast of Japan. Linear regression models
      (separate for each gender and cohort) of SF-36 mental component scores were
      analysed with role combinations, family-to-work and work-to-family conflict as
      explanatory variables. RESULTS: Single fathers in all three cohorts and of single
      mothers in the Helsinki cohort had poor mental health, and this was partly
      explained by their higher levels family-to-work conflict. Both types of conflict
      affect the mental health of men and women independently of each other. Japanese
      women had the greatest conflict and poorest mental health while Helsinki women
      had the lowest conflict and best mental health. CONCLUSION: Both work-to-family
      and family-to-work conflict affect the mental health of men and women in three
      different countries. Work and family roles and the balance between the two may be
      important for the mental health of men and women in industrialized societies. Any
      analysis of the effect of multiple roles on health needs to take into account the
      psychosocial content of such roles.

PMID- 15166201
TI  - Commentary: the hormone replacement-coronary heart disease conundrum: is this the
      death of observational epidemiology?

PMID- 15166202
TI  - Commentary: observation versus intervention--what's different?

PMID- 15166203
TI  - Commentary: hazards of studying women: the oestrogen oestrogen/progesterone
      dilemma.

PMID- 15166204
TI  - Commentary: the HRT story: vindication of old epidemiological theory.

PMID- 15166205
TI  - Low birthweight and Type 2 diabetes: a study on 11 162 Swedish twins.
AB  - BACKGROUND: To investigate the association between low birthweight and diabetes
      in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed
      Swedish twins born between 1906 and 1958 was used in order to investigate the
      risk of developing Type 2 diabetes between and within twin pairs by utilizing
      random effects linear models. RESULTS: Between pairs there was a significant
      increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean
      birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass
      index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P =
      0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of
      the heterogeneity of the within and between effects showed no significant
      difference between the estimates. CONCLUSIONS: The study suggests that reduced
      fetal growth increase the risk of Type 2 diabetes due to an in utero programming
      effect possibly caused by intrauterine malnutrition. However, it does not exclude
      the possibility of a common genetic mechanism.

PMID- 15166206
TI  - Birthweight and work participation in adulthood.
AB  - BACKGROUND: In a number of studies, birthweight has been associated with
      cognition and educational attainment into adult age. However, the association is
      not clear between birthweight and work participation in adulthood. We
      investigated this association assessing to which extent it was influenced by
      circumstances concerning family background or disease in early life. METHODS:
      Through linkage between several national registers containing personal
      information from birth into adult age we established a longitudinal, population
      based cohort study. Study participants were all 308 829 singletons born in Norway
      in 1967-1971 as registered by the Medical Birth Registry of Norway who were
      national residents at age 29. The study outcome was unemployment defined as a
      lack of personal income among people who were not under education in the calendar
      year of their 29th birthday as registered by the National Insurance
      Administration and Statistics Norway. RESULTS: Birthweight below the standardized
      mean was associated with unemployment. The risk of unemployment increased by
      decreasing birthweight for both women and men and also after adjustment for
      potential confounding factors. The association was evident both in people with or
      without social disadvantage, as well as people with or without childhood disease.
      Still, birthweight below the standardized mean explained much less of the
      unemployment risk than did social disadvantage (attributable fractions 8.0%
      versus 28.3% for women and 10.0% versus 40.2% for men). CONCLUSION: Birthweight
      below the standardized mean was independently associated with unemployment at age
      29, also in the normal birthweight range.

PMID- 15166207
TI  - Using capture-recapture methods to study recent transmission of tuberculosis.

PMID- 15166208
TI  - Intrauterine famine exposure and body proportions at birth: the Dutch Hunger
      Winter.
AB  - BACKGROUND: Fetal programming of adult disease may be a long-term effect of fetal
      nutrition. Expected short-term effects include changes in body size and
      proportions at birth. The specific responses of fetal growth to acute
      undernutrition at varying points in pregnancy are still unclear. METHODS: We
      abstracted all birth records of infants born in two midwife training schools in
      the western Netherlands between 1 October 1944 and 31 March 1946, and compared
      infants whose mothers were exposed to the Dutch famine of 1944-1945 during
      specific trimesters of pregnancy with control infants born in 1943. We considered
      birthweight (BWT), crown-to-heel length (CHL), head circumference (HC), and ratio
      and regression-adjusted measures of these parameters. RESULTS: BWT, CHL, and HC
      declined with famine exposure late in pregnancy. Changes in WT for CHL paralleled
      changes in WT alone in size and direction. Results for HC were inconsistent,
      varying by choice of body size adjustor (WT or CHL), and by method of adjustment
      (ratio or regression). BWT, CHL, and HC did not change with first trimester
      famine exposure. CONCLUSION: Even under famine conditions, birth size and body
      proportions vary only with late pregnancy exposure. HC for body size has the
      added disadvantage that late pregnancy exposure effects vary drastically with
      choice of measure. We do not recommend the use of birth size or body proportions
      as a proxy for fetal nutritional status in the study of adult disease.

PMID- 15166209
TI  - Exposure over the life course to an urban environment and its relation with
      obesity, diabetes, and hypertension in rural and urban Cameroon.
AB  - BACKGROUND: This study aimed to assess the association between lifetime exposure
      to urban environment (EU) and obesity, diabetes, and hypertension in an adult
      population of Sub-Saharan Africa. METHODS: We studied 999 women and 727 men aged
      > or =25 years. They represent all the adults aged > or =25 years living in
      households randomly selected from a rural and an urban community of Cameroon with
      a 98% and 96% participation rate respectively. Height, weight, blood pressure,
      and fasting blood glucose were measured in all subjects. Current levels of
      physical activity (in metabolic equivalents [MET]) were evaluated through the Sub
      Saharan African Activity Questionnaire. Chronological data on lifetime migration
      were collected retrospectively and expressed as the total (EUt) or percentage
      (EU%) of lifetime exposure to urban environment. RESULTS: Lifetime EUt was
      associated with body mass index (BMI) (r = 0.42; P < 0.0001), fasting glycaemia
      (r = 0.23; P < 0.0001), and blood pressure (r = 0.17; P < 0.0001) but not with
      age. The subjects who recently settled in a city (< or =2 years) had higher BMI
      (+2.9 kg/m(2); P < 0.001), fasting glycaemia (+0.8 mmol/l; P < 0.001), systolic
      (+23 mmHg; P < 0.001) and diastolic (+9 mmHg; P = 0.001) blood pressure than
      rural dwellers with a history of 2 years EU. EU during the first 5 years of life
      was not, on its own, associated with glycaemia or BMI. However, both lifetime EUt
      and current residence were independently associated with obesity and diabetes.
      The association between lifetime EUt and hypertension was not independent of
      current residence and current level of physical activity. CONCLUSIONS: This study
      suggests that for the study of obesity and diabetes, in addition to current
      residence, both lifetime exposure to an urban environment and recent migration
      history should be investigated.

PMID- 15166210
TI  - Factor analysis of household factors: are they associated with respiratory
      conditions in Chinese children?
AB  - BACKGROUND: We explored methods to develop uncorrelated variables for
      epidemiological analysis models. They were used to examine associations between
      respiratory health outcomes and multiple household risk factors. METHODS: We
      analysed data collected in the Four Chinese Cities Study (FCCS) to examine health
      effects on prevalence rates of respiratory symptoms and illnesses in 7058 school
      children living in the four Chinese cities: Lanzhou, Chongqing, Wuhan, and
      Guangzhou. We used factor analysis approaches to reduce the number of the
      children's lifestyle/household variables and to develop new uncorrelated 'factor'
      variables. We used unconditional logistic regression models to examine
      associations between the factor variables and the respiratory health outcomes,
      while controlling for other covariates. RESULTS: Five factor variables were
      derived from 21 original variables: heating coal smoke, cooking coal smoke,
      socioeconomic status, ventilation, and environmental tobacco smoke (ETS) and
      parental asthma. We found that higher exposure to heating coal smoke was
      associated with higher reporting of cough with phlegm, wheeze, and asthma.
      Cooking coal smoke was not associated with any of the outcomes. Lower
      socioeconomic status was associated with lower reporting of persistent cough and
      bronchitis. Higher household ventilation was associated with lower reporting of
      persistent cough, persistent phlegm, cough with phlegm, bronchitis, and wheeze.
      Higher exposure to ETS and the presence of parental asthma were associated with
      higher reporting of persistent cough, persistent phlegm, cough with phlegm,
      bronchitis, wheeze, and asthma. CONCLUSIONS: Our study suggests that independent
      respiratory effects of exposure to indoor air pollution, heating coal smoke, and
      ETS may exist for the studied children.

PMID- 15166211
TI  - The limits of epidemiology and the Spanish Toxic Oil Syndrome.

PMID- 15166212
TI  - Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC
      VR1310.

PMID- 15166213
TI  - Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis.
      Cross-compartment protection by CuZn-superoxide dismutase.
AB  - Among the phenotypes of Saccharomyces cerevisiae mutants lacking CuZn-superoxide
      dismutase (Sod1p) is an aerobic lysine auxotrophy; in the current work we show an
      additional leaky auxotrophy for leucine. The lysine and leucine biosynthetic
      pathways each contain a 4Fe-4S cluster enzyme homologous to aconitase and likely
      to be superoxide-sensitive, homoaconitase (Lys4p) and isopropylmalate dehydratase
      (Leu1p), respectively. We present evidence that direct aerobic inactivation of
      these enzymes in sod1 Delta yeast results in the auxotrophies. Located in the
      cytosol and intermembrane space of the mitochondria, Sod1p likely provides direct
      protection of the cytosolic enzyme Leu1p. Surprisingly, Lys4p does not share a
      compartment with Sod1p but is located in the mitochondrial matrix. The activity
      of a second matrix protein, the tricarboxylic acid cycle enzyme aconitase, was
      similarly lowered in sod1 Delta mutants. We measured only slight changes in total
      mitochondrial iron and found no detectable difference in mitochondrial "free"
      (EPR-detectable) iron making it unlikely that a gross defect in mitochondrial
      iron metabolism is the cause of the decreased enzyme activities. Thus, we
      conclude that when Sod1p is absent a lysine auxotrophy is induced because Lys4p
      is inactivated in the matrix by superoxide that originates in the intermembrane
      space and diffuses across the inner membrane.

PMID- 15166214
TI  - Cross-talk between thiamin diphosphate binding and phosphorylation loop
      conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase.
AB  - The decarboxylase/dehydrogenase (E1b) component of the 4-megadalton human
      branched-chain alpha-keto acid dehydrogenase (BCKD) metabolic machine is a
      thiamin diphosphate (ThDP)-dependent enzyme with a heterotetrameric cofactor
      binding fold. The E1b component catalyzes the decarboxylation of alpha-keto acids
      and the subsequent reductive acylation of the lipoic acid-bearing domain (LBD)
      from the 24-meric transacylase (E2b) core. In the present study, we show that the
      binding of cofactor ThDP to the E1b active site induces a disorder-to-order
      transition of the conserved phosphorylation loop carrying the two phosphorylation
      sites Ser(292)-alpha and Ser(302)-alpha, as deduced from the 1.80-1.85 A apoE1b
      and holoE1b structures. The induced loop conformation is essential for the
      recognition of lipoylated LBD to initiate E1b-catalyzed reductive acylation.
      Alterations of invariant Arg(287)-alpha, Asp(295)-alpha, Tyr(300)-alpha, and
      Arg(301)-alpha that form a hydrogen-bonding network in the phosphorylation loop
      result in the disordering of the loop conformation as elucidated by limited
      proteolysis, accompanied by the impaired binding and diminished reductive
      acylation of lipoylated LBD. In contrast, k(cat) values for E1b-catalyzed
      decarboxylation of the alpha-keto acid are higher in these E1b mutants than in
      wild-type E1b, with higher K(m) values for the substrate in the mutants. ThDP
      binding that orders the loop prevents phosphorylation of E1b by the BCKD kinase
      and averts the inactivation of wild-type E1b, but not the above mutants, by this
      covalent modification. Our results establish that the cross-talk between the
      bound ThDP and the phosphorylation loop conformation serves as a feed-forward
      switch for multiple reaction steps in the BCKD metabolic machine.

PMID- 15166215
TI  - A feedback loop in the polo-like kinase activation pathway.
AB  - The Xenopus polo-like kinase Plx1 plays important roles during entry into and
      exit from mitosis (M phase). Previous studies revealed that Plx1 is activated by
      phosphorylation on serine and threonine residues, and purification of an
      activating enzyme from mitotic Xenopus egg extracts led to cloning and
      characterization of Xenopus polo-like kinase kinase (xPlkk1), which can
      phosphorylate and activate Plx1 in vitro. In the present study, a positive
      feedback loop between Plx1 and xPlkk1 was shown to result in each kinase
      phosphorylating and activating the other. Sequencing of radiolabeled xPlkk1 after
      phosphorylation by Plx1 in vitro identified three phosphorylation sites each
      spaced three amino acids apart, two of which have the consensus acidic-X-pSer
      hydrophobic described for other polo-like kinase substrates. In addition,
      endogenous xPlkk1 in oocytes was phosphorylated on these sites in M phase but not
      in interphase. A mutant xPlkk1 in which these three amino acids were changed to
      alanine (xPlkk1(SA3)) was unable to be phosphorylated or activated in vitro by
      Plxl. Depletion of Plx1 from oocyte extracts prior to stimulation of the G(2)/M
      transition blocked the activation of xPlkk1, but depletion of xPlkk1 before
      stimulation did not block Plx1 activation. These results indicate that xPlkk1 may
      function downstream as a target of Plx1 rather than as an upstream activating
      kinase during the G(2)/M transition.

PMID- 15166216
TI  - Structural basis for inhibition of Aspergillus niger xylanase by triticum
      aestivum xylanase inhibitor-I.
AB  - Plants developed a diverse battery of defense mechanisms in response to continual
      challenges by a broad spectrum of pathogenic microorganisms. Their defense
      arsenal includes inhibitors of cell wall-degrading enzymes, which hinder a
      possible invasion and colonization by antagonists. The structure of Triticum
      aestivum xylanase inhibitor-I (TAXI-I), a first member of potent TAXI-type
      inhibitors of fungal and bacterial family 11 xylanases, has been determined to
      1.7-A resolution. Surprisingly, TAXI-I displays structural homology with the
      pepsin-like family of aspartic proteases but is proteolytically nonfunctional,
      because one or more residues of the essential catalytical triad are absent. The
      structure of the TAXI-I. Aspergillus niger xylanase I complex, at a resolution of
      1.8 A, illustrates the ability of tight binding and inhibition with subnanomolar
      affinity and indicates the importance of the C-terminal end for the differences
      in xylanase specificity among different TAXI-type inhibitors.

PMID- 15166217
TI  - Ubiquitination and proteasomal degradation of the BRCA1 tumor suppressor is
      regulated during cell cycle progression.
AB  - The BRCA1 tumor suppressor and the BARD1 protein form a stable heterodimeric
      complex that can catalyze the formation of polyubiquitin chains. Expression of
      BRCA1 fluctuates in a cell cycle-dependent manner, such that low steady-state
      levels of BRCA1 gene products are found in resting cells and early G1 cycling
      cells and high levels in S and G2 phase cells. Although transcriptional
      activation of the BRCA1 gene can account for induction of BRCA1 expression at the
      G1/S transition, the mechanisms by which BRCA1 is down-regulated during cell
      cycle progression have not been addressed. Here we show that the steady-state
      levels of BRCA1 protein remain elevated throughout mitosis but begin to decline
      at the M/G1 transition. This decline in BRCA1 levels coincides with the
      appearance of proteasome-sensitive ubiquitin conjugates of BRCA1 at the onset of
      G1. Formation of these conjugates occurs throughout G1 and S, but not in cells
      arrested in prometaphase by nocodazole. The proteasome-sensitive ubiquitin
      conjugates of BRCA1 appear to be distinct from BRCA1 autoubiquitination products
      and are probably catalyzed by the action of other cellular E3 ligases.
      Interestingly, co-expression of BARD1 inhibits the formation of these conjugates,
      suggesting that BARD1 serves to stabilize BRCA1 expression in part by reducing
      proteasome-sensitive ubiquitination of BRCA1 polypeptides. In summary, these data
      indicate that the cell cycle-dependent pattern of BRCA1 expression is determined
      in part by ubiquitin-dependent proteasomal degradation.

PMID- 15166218
TI  - Three different oxygen-induced radical species in endothelial nitric-oxide
      synthase oxygenase domain under regulation by L-arginine and tetrahydrobiopterin.
AB  - Endothelial nitric-oxide synthase (eNOS) plays important roles in vascular
      physiology and homeostasis. Whether eNOS catalyzes nitric oxide biosynthesis or
      the synthesis of reactive oxygen species such as superoxide, hydrogen peroxide,
      and peroxynitrite is dictated by the bioavailability of tetrahydrobiopterin
      (BH(4)) and L-arginine during eNOS catalysis. The effect of BH(4) and L-arginine
      on oxygen-induced radical intermediates has been investigated by single turnover
      rapid-freeze quench and EPR spectroscopy using the isolated eNOS oxygenase domain
      (eNOS(ox)). Three distinct radical intermediates corresponding to >50% of the
      heme were observed during the reaction between ferrous eNOS(ox) and oxygen. BH(4)
      free eNOS(ox) produced the superoxide radical very efficiently in the absence of
      L-arginine. L-Arginine decreased the formation rate of superoxide by an order of
      magnitude but not its final level or EPR line shape. For BH(4)-containing
      eNOS(ox), only a stoichiometric amount of BH(4) radical was produced in the
      presence of L-arginine, but in its absence a new radical was obtained. This new
      radical could be either a peroxyl radical of BH(4) or an amino acid radical was
      in the vicinity of the heme. Formation of this new radical is very rapid, >150 s(
      1), and it was subsequently converted to a BH(4) radical. The trapping of the
      superoxide radical by cytochrome c in the reaction of BH(4)(-) eNOS(ox) exhibited
      a limiting rate of approximately 15 s(-1), the time for the superoxide radical to
      leave the heme pocket and reach the protein surface; this reveals a general
      problem of the regular spin-trapping method in determining radical formation
      kinetics. Cytochrome c failed to trap the new radical species. Together with
      other EPR characteristics, our data strongly support the conclusion that this new
      radical is not a superoxide radical or a mixture of superoxide and biopterin
      radicals. Our study points out distinct roles of BH(4) and L-arginine in
      regulating eNOS radical intermediates. BH(4) prevented superoxide formation by
      chemical conversions of the Fe(II)O(2) intermediate, and l-arginine delayed
      superoxide formation by electronic interaction with the heme-bound oxygen.

PMID- 15166219
TI  - Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of
      protein sumoylation by cellular stresses.
AB  - We have undertaken a global analysis of sumoylated proteins in Saccharomyces
      cerevisiae by tandem mass spectrometry. Exposure of cells to oxidative and
      ethanol stresses caused large increases in protein sumoylation. A large number of
      new sumoylated proteins were identified in untreated, hydrogen peroxide-treated,
      and ethanol-treated cells. These proteins are known to be involved in diverse
      cellular processes, including gene transcription, protein translation, DNA
      replication, chromosome segregation, metabolic processes, and stress responses.
      Additionally, the known enzymes, including E1, E2, and E3 of the sumoylation
      cascade were found to be auto-sumoylated. Taken together, these results show that
      protein sumoylation is broadly involved in many cellular functions and this mass
      spectrometry-based proteomic approach is useful in studying the regulation of
      protein sumoylation in the cells.

PMID- 15166220
TI  - Role of the interleukin (IL)-28 receptor tyrosine residues for antiviral and
      antiproliferative activity of IL-29/interferon-lambda 1: similarities with type I
      interferon signaling.
AB  - Interferon (IFN)-lambda 1, -lambda 2, and -lambda 3 are the latest members of the
      class II cytokine family and were shown to have antiviral activity. Their
      receptor is composed of two chains, interleukin-28R/likely interleukin or
      cytokine or receptor 2 (IL-28R/LICR2) and IL-10R beta, and mediates the tyrosine
      phosphorylation of STAT1, STAT2, STAT3, and STAT5. Here, we show that activation
      of this receptor by IFN-lambda 1 can also inhibit cell proliferation and induce
      STAT4 phosphorylation, further extending functional similarities with type I
      IFNs. We used IL-28R/LICR2-mutated receptors to identify the tyrosines required
      for STAT activation, as well as antiproliferative and antiviral activities. We
      found that IFN-lambda 1-induced STAT2 tyrosine phosphorylation is mediated
      through tyrosines 343 and 517 of the receptor, which showed some similarities
      with tyrosines from type I IFN receptors involved in STAT2 activation. These two
      tyrosines were also responsible for antiviral and antiproliferative activities of
      IFN-lambda 1. By contrast, STAT4 phosphorylation (and to some extent STAT3
      activation) was independent from IL-28R/LICR2 tyrosine residues. Taken together,
      these observations extend the functional similarities between IFN-lambdas and
      type I IFNs and shed some new light on the mechanisms of activation of STAT2 and
      STAT4 by these cytokines.

PMID- 15166221
TI  - Rap1 regulates E-cadherin-mediated cell-cell adhesion.
AB  - The small GTPase Rap is best characterized as a critical regulator of integrin
      mediated cell adhesion, although its mechanism of action is not understood. Rap
      also influences the properties of other cell-surface receptors and biological
      processes, although whether these are a consequence of effects on integrins is
      not clear. We show here that Rap also plays an important role in the regulation
      of cadherin-mediated cell-cell adhesion in epithelial cells. Expression of
      constitutively active Rap1A restored cadherin-mediated cell-cell contacts in
      mesenchymal Ras-transformed Madin-Darby canine kidney cells, resulting in
      reversion to an epithelial phenotype. Activation of endogenous Rap via the Rap
      exchange factor Epac1 also antagonized hepatocyte growth factor-induced
      disruption of adherens junctions. Inhibition of Rap signaling resulted in
      disruption of epithelial cell-cell contacts. Rap activity was required for
      adhesion of cells to recombinant E-cadherin extracellular domains, i.e. in the
      absence of integrin-mediated adhesion. These findings suggest that Rap signaling
      positively contributes to cadherin-mediated adhesion and that this occurs
      independently of effects on integrin-mediated adhesion. Our results imply that
      Rap may function in a broader manner to regulate the function of cell-surface
      adhesion receptors.

PMID- 15166222
TI  - Differential current decay profiles of epithelial sodium channel subunit
      combinations in polarized renal epithelial cells.
AB  - In many epithelial tissues in the body, the rate of Na(+) reabsorption is
      governed by the activity of the epithelial sodium channel (ENaC). The assembly,
      trafficking, and turnover of the three ENaC subunits (alpha, beta, and gamma) is
      complex and not well understood. Recent experiments suggest that ENaC must be
      proteolytically cleaved for maximal activity and may explain the discrepancies
      reported in prior biochemical approaches focused on quantitating the trafficking
      and half-life of full-length subunits. As an alternative approach to examining
      the dynamics of ENaC subunits, we have generated doxycycline-repressible
      replication-defective recombinant adenoviruses encoding individual epitope-tagged
      mouse ENaC subunits and expressed these in polarized MDCK I cells. Co-infection
      with these viruses encoding all three subunits generates robust amiloride
      sensitive currents in polarized MDCK cells. Significant current was also observed
      in cells expressing alpha- and gamma-mENaC in the absence of beta-mENaC. These
      currents did not appear to result from association with endogenous canine beta
      ENaC. Treatment of alpha beta gamma-expressing cells with cycloheximide (CHX)
      resulted in the rapid inhibition (within 3 h) of approximately 50-80% of the
      initial current; however, a sizable fraction of the initial current remained even
      after 6 h of CHX. By contrast, CHX addition to cells expressing only alpha- and
      gamma-mENaC resulted in rapid decay in current with no residual fraction. Our
      data suggest that ENaC channels of differing stoichiometries are differentially
      trafficked and degraded and provide support for the possibility that
      noncoordinate trafficking of ENaC subunits may function in vivo as a mechanism to
      modulate ENaC activity.

PMID- 15166224
TI  - The modular adaptor protein ARH is required for low density lipoprotein (LDL)
      binding and internalization but not for LDL receptor clustering in coated pits.
AB  - ARH is an adaptor protein required for efficient endocytosis of low density
      lipoprotein (LDL) receptors (LDLRs) in selected tissues. Individuals lacking ARH
      (ARH-/-) have severe hypercholesterolemia due to impaired hepatic clearance of
      LDL. Immortalized lymphocytes, but not fibroblasts, from ARH-deficient subjects
      fail to internalize LDL. To further define the role of ARH in LDLR function, we
      compared the subcellular distribution of the LDLR in lymphocytes from normal and
      ARH-/- subjects. In normal lymphocytes LDLRs were predominantly located in
      intracellular compartments, whereas in ARH-/- cells the receptors were almost
      exclusively on the plasma membrane. Biochemical assays and quantification of LDLR
      by electron microscopy indicated that ARH-/- lymphocytes had >20-fold more LDLR
      on the cell surface and a approximately 27-fold excess of LDLR outside of coated
      pits. The accumulation of LDLR on the cell surface was not due to failure of
      receptors to localize in coated pits since the number of LDLRs in coated pits was
      similar in ARH-/- and normal cells. Despite the dramatic increase in cell surface
      receptors, LDL binding was only 2-fold higher in the ARH-/- lymphocytes. These
      findings indicate that ARH is required not only for internalization of the
      LDL.LDLR complex but also for efficient binding of LDL to the receptor and
      suggest that ARH stabilizes the associations of the receptor with LDL and with
      the invaginating portion of the budding pit, thereby increasing the efficiency of
      LDL internalization.

PMID- 15166223
TI  - Phosphorylation of the histone deacetylase 7 modulates its stability and
      association with 14-3-3 proteins.
AB  - Class II histone deacetylases (HDACs) play a role in myogenesis and inhibit
      transcriptional activation by myocyte enhancer factors 2. A distinct feature of
      class II HDACs is their ability to shuttle between the nucleus and the cytoplasm
      in a cell type- and signal-dependent manner. We demonstrate here that treatment
      with the 26 S proteosome inhibitors, MG132 and ALLN, leads to detection of
      ubiquitinated HDAC7 and causes accumulation of cytoplasmic HDAC7. We also show
      that treatment with calyculin A, a protein phosphatase inhibitor, leads to a
      marked increase of HDAC7 but not HDAC5. The increase in HDAC7 is accompanied by
      enhanced interaction between 14-3-3 proteins and HDAC7. HDAC7 mutations that
      prevent the interaction with 14-3-3 proteins also block calyculin A-mediated
      stabilization. Expression of constitutively active calcium/calmodulin-dependent
      kinase I stabilizes HDAC7 and causes an increased association between HDAC7 and
      14-3-3. Together, our results suggest that calcium/calmodulin-dependent kinase I
      mediated phosphorylation of HDAC7 acts, in part, to promote association of HDAC7
      with 14-3-3 and stabilizes HDAC7.

PMID- 15166225
TI  - Mechanisms of interactions of factor X and factor Xa with the acidic region in
      the factor VIII A1 domain.
AB  - The 337-372 sequence of the factor VIIIa A1 subunit contains interactive sites
      for both zymogen factor X and the active enzyme, factor Xa. Solid phase binding
      studies indicated that factor Xa possessed a >20-fold higher affinity for the
      isolated A1 subunit of factor VIIIa compared with factor X. Heparin completely
      inhibited zero-length cross-linking of the 337-372 peptide to factor Xa but not
      to factor X. In the presence of calcium, factor Xa showed greater affinity for
      heparin than factor X. Studies using factor Xa mutants in which heparin-binding
      exosite residues were individually replaced by Ala showed that the R240A mutant
      was defective in recognition of the Lys36 cleavage site, generating the A137-372
      intermediate with approximately 20% the catalytic efficiency of wild type. This
      defect likely resulted from an approximately 4-fold increase in Km for the A1
      substrate because kcat values for the wild type and mutant were equivalent.
      Cleavage of the A1-A2 domain junction by factor Xa R240A was not blocked by the
      337-372 peptide. Studies using mutant factor VIII where clustered acidic residues
      in the 337-372 segment were replaced by Ala showed that a factor VIIIa
      D361A/D362A/D363A mutant possessed a approximately 1.6-fold increase in Km for
      factor X compared with wild type. However, similar Km values were observed for
      recombinant factor X and R240A substrates. These results indicate that the
      binding regions of factor X and factor Xa for A1 domain overlap and that both
      utilize acidic residues 361-363. Furthermore, factor Xa but not factor X
      interacts with high affinity at this site via residues contained within the
      heparin-binding exosite of the proteinase.

PMID- 15166226
TI  - Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease.
AB  - Short term high fat feeding in rats results specifically in hepatic fat
      accumulation and provides a model of non-alcoholic fatty liver disease in which
      to study the mechanism of hepatic insulin resistance. Short term fat feeding (FF)
      caused a approximately 3-fold increase in liver triglyceride and total fatty acyl
      CoA content without any significant increase in visceral or skeletal muscle fat
      content. Suppression of endogenous glucose production (EGP) by insulin was
      diminished in the FF group, despite normal basal EGP and insulin-stimulated
      peripheral glucose disposal. Hepatic insulin resistance could be attributed to
      impaired insulin-stimulated IRS-1 and IRS-2 tyrosine phosphorylation. These
      changes were associated with activation of PKC-epsilon and JNK1. Ultimately,
      hepatic fat accumulation decreased insulin activation of glycogen synthase and
      increased gluconeogenesis. Treatment of the FF group with low dose 2,4
      dinitrophenol to increase energy expenditure abrogated the development of fatty
      liver, hepatic insulin resistance, activation of PKC-epsilon and JNK1, and
      defects in insulin signaling. In conclusion, these data support the hypothesis
      hepatic steatosis leads to hepatic insulin resistance by stimulating
      gluconeogenesis and activating PKC-epsilon and JNK1, which may interfere with
      tyrosine phosphorylation of IRS-1 and IRS-2 and impair the ability of insulin to
      activate glycogen synthase.

PMID- 15166227
TI  - RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src
      independent manner.
AB  - The related adhesion focal tyrosine kinase (RAFTK), also known as Pyk2, undergoes
      autophosphorylation upon its stimulation. This leads to cascades of intracellular
      signaling that result in the regulation of various cellular activities. However,
      the molecular mechanism of RAFTK autophosphorylation is not yet known. Using
      various RAFTK constructs fused with two different tags, we found that the
      autophosphorylation of RAFTK was mediated by a trans-acting mechanism, not a cis
      acting mechanism. In addition, overexpression of kinase-mutated RAFTK inhibited
      wild type RAFTK autophosphorylation in a dose-dependent manner by a trans-acting
      interaction. Trans-acting autophosphorylation was also observed between
      endogenous and exogenous RAFTK upon potassium depolarization of neuroendocrine
      PC12 cells. Using immunoprecipitation and affinity chromatography, we detected
      RAFTK self-association that was not affected by deletion of a single region or
      domain of RAFTK. Furthermore, RAFTK autophosphorylation occurred only at site
      Tyr402 in a Src kinase activity-independent manner. However, Src significantly
      enhanced RAFTK-mediated paxillin phosphorylation, suggesting a key role for Src
      in RAFTK activation and phosphorylation of downstream substrates. Our results
      indicate that the activation of RAFTK occurs in several steps. First, upon
      stimulus, RAFTK trans-autophosphorylates Tyr402. Second, phosphorylated Tyr402
      recruits and activates Src kinase that in turn phosphorylates RAFTK and enhances
      its kinase activity. Lastly, the enhanced RAFTK activity induces the activation
      of downstream signaling molecules. Taken together, these studies provide insights
      into the molecular mechanism of RAFTK autophosphorylation and the specific role
      of Src in the regulation of RAFTK activation.

PMID- 15166228
TI  - Fibroblast growth factor-2 and remodeled type I collagen control membrane
      protrusion in human vascular smooth muscle cells: biphasic activation of Rac1.
AB  - Plasma membrane protrusion is fundamental to cell motility, but its regulation by
      the extracellular environment is not well elucidated. We have quantified
      lamellipodial protrusion dynamics in human vascular smooth muscle cells exposed
      to fibroblast growth factor 2 (FGF-2) and type I collagen, two distinct ligands
      presented to vascular cells during arterial remodeling. Video microscopy revealed
      that FGF-2 stimulated a modest increase in lamellipodial protrusion rate that
      peaked within 15 min. This response was associated with immediate but transient
      activation of Rac1 and was inhibited in cells infected with retrovirus containing
      cDNA encoding dominant-negative Rac1. A 1-h exposure to FGF-2 also set up a
      second phase of more striking lamellipodial protrusion evident at 24-36 h. This
      delayed response was most pronounced when cells were on type 1 collagen and was
      associated with FGF-2-induced expression of collagenase-1 that localized to the
      edge of protruding lamellipodia. Moreover, late membrane protrusion was inhibited
      when cells were on collagenase-resistant type I collagen, implicating degraded
      collagen as a mediator. For cells on collagen, the immediate activation of Rac1
      by FGF-2 was followed by a sustained wave of Rac1 activation that was inhibited
      when cleavage of the collagen triple helix was prevented and also by blockade of
      alpha(v)beta(3) integrin. We conclude that lamellipodial protrusion in smooth
      muscle cells can be regulated by waves of Rac1 activation, corresponding to the
      sequential presentation of FGF-2 and remodeled collagen. The findings thus reveal
      a previously unrecognized level of coordination among extracellular input that
      enables cells to maintain protrusive activity over prolonged periods.

PMID- 15166229
TI  - Functional domain and motif analyses of androgen receptor coregulator ARA70 and
      its differential expression in prostate cancer.
AB  - Androgen receptor (AR)-associated coregulator 70 (ARA70) was the first identified
      AR coregulator. However, its molecular mechanism and biological relevance to
      prostate cancer remain unclear. Here we show that ARA70 interacts with and
      promotes AR activity via the consensus FXXLF motif within the ARA70-N2 domain
      (amino acids 176-401). However, it does not promote AR activity via the classic
      LXXLL motif located at amino acids 92-96, although this classic LXXLL motif is
      important for ARA70 to interact with other receptors, such as PPARgamma. The
      molecular mechanisms by which ARA70 enhances AR transactivation involve the
      increase of AR expression, protein stability, and nuclear translocation.
      Furthermore, ARA70 protein is more frequently detected in prostate cancer
      specimens (91.74%) than in benign tissues (64.64%, p < 0.0001). ARA70 expression
      is also increased in high-grade prostate cancer tissues as well as the hormone
      refractory LNCaP xenografts and prostate cancer cell lines. Because ARA70 can
      promote the antiandrogen hydroxyflutamide (HF)-enhanced AR transactivation, the
      increased ARA70 expression in hormone-refractory prostate tumors may confer the
      development of HF withdrawal syndrome, commonly diagnosed in patients with the
      later stages of prostate cancer. Because ARA70-N2 containing the AR-interacting
      FXXLF motif without coactivation function can suppress HF-enhanced AR
      transactivation in the hormone-refractory LNCaP cells, using the ARA70-N2
      inhibitory peptide at the hormone refractory stage to battle the HF withdrawal
      syndrome may become an alternative strategy to treat prostate cancer.

PMID- 15166230
TI  - Intracellular delivery of phosphatidylinositol (3,4,5)-trisphosphate causes
      incorporation of glucose transporter 4 into the plasma membrane of muscle and fat
      cells without increasing glucose uptake.
AB  - Insulin stimulates glucose uptake into muscle and fat cells by translocating
      glucose transporter 4 (GLUT4) to the cell surface, with input from
      phosphatidylinositol (PI) 3-kinase and its downstream effector Akt/protein kinase
      B. Whether PI 3,4,5-trisphosphate (PI(3,4,5)P(3)) suffices to produce GLUT4
      translocation is unknown. We used two strategies to deliver PI(3,4,5)P(3)
      intracellularly and two insulin-sensitive cell lines to examine Akt activation
      and GLUT4 translocation. In 3T3-L1 adipocytes, the acetoxymethyl ester of
      PI(3,4,5)P(3) caused GLUT4 migration to the cell periphery and increased the
      amount of plasma membrane-associated phospho-Akt and GLUT4. Intracellular
      delivery of PI(3,4,5)P(3) using polyamine carriers also induced translocation of
      myc-tagged GLUT4 to the surface of intact L6 myoblasts, demonstrating membrane
      insertion of the transporter. GLUT4 translocation caused by carrier-delivered
      PI(3,4,5)P(3) was not reproduced by carrier-PI 4,5-bisphosphate or carrier alone.
      Like insulin, carrier-mediated delivery of PI(3,4,5)P(3) elicited redistribution
      of perinuclear GLUT4 and Akt phosphorylation at the cell periphery. In contrast
      to its effect on GLUT4 mobilization, delivered PI(3,4,5)P(3) did not increase 2
      deoxyglucose uptake in either L6GLUT4myc myoblasts or 3T3-L1 adipocytes. The
      ability of exogenously delivered PI(3,4,5)P(3) to augment plasma membrane GLUT4
      content without increasing glucose uptake suggests that input at the level of PI
      3-kinase suffices for GLUT4 translocation but is insufficient to stimulate
      glucose transport.

PMID- 15166231
TI  - The synergistic effect of dexamethasone and all-trans-retinoic acid on hepatic
      phosphoenolpyruvate carboxykinase gene expression involves the coactivator p300.
AB  - Activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription in
      response to all-trans-retinoic acid (RA) or a glucocorticoid such as
      dexamethasone (Dex) requires a distinct arrangement of DNA-response elements and
      their cognate transcription activators on the gene promoter. Two of the accessory
      factor-binding elements involved in the Dex response (gAF1 and gAF3) coincide
      with the DNA-response elements involved in the RA response. We demonstrate here
      that the combination of Dex/RA has a synergistic effect on endogenous PEPCK gene
      expression in rat hepatocytes and H4IIE hepatoma cells. Reporter gene studies
      show that the gAF3 element and one of the two glucocorticoid receptor-binding
      elements (GR1) are most important for this effect. Chromatin immunoprecipitation
      assays revealed that when H4IIE cells were treated with Dex/RA, ligand-activated
      retinoic acid receptors (retinoic acid receptor/retinoid X receptor) and
      glucocorticoid receptors are recruited to this gene promoter, as are the
      transcription coregulators p300, CREB-binding protein, p/CIP, and SRC-1. Notably,
      the recruitment of p300 and RNA polymerase II to the PEPCK promoter is increased
      by the combined Dex/RA treatment compared with Dex or RA treatment alone. The
      functional importance of p300 in the Dex/RA response is illustrated by the
      observation that selective reduction of this coactivator, but not that of CREB
      binding protein, abolishes the synergistic effect in H4IIE cells.

PMID- 15166233
TI  - Oxidative damage to specific proteins in replicative and chronological-aged
      Saccharomyces cerevisiae: common targets and prevention by calorie restriction.
AB  - Oxidative modifications of cellular components have been described as one of the
      main contributions to aged phenotype. In Saccharomyces cerevisiae, two distinct
      life spans can be considered, replicative and chronological. The relationship
      between both aging models is still not clear despite suggestions that these
      phenomena may be related. In this work, we show that replicative and
      chronological-aged yeast cells are affected by an oxidative stress situation
      demonstrated by increased protein carbonylation when compared with young cells.
      The data on the identification of these oxidatively modified proteins gives clues
      to better understand cellular dysfunction that occurs during aging. Strikingly,
      although in both aging models metabolic differences are important, major targets
      are almost the same. Common targets include stress resistance proteins (Hsp60 and
      Hsp70) and enzymes involved in glucose metabolism such as enolase,
      glyceraldehydes-3-P dehydrogenase, fructose-1,6-biphosphate aldolase, pyruvate
      decarboxylase, and alcohol dehydrogenase. In both aging models, calorie
      restriction results in decreased damage to these proteins. In addition,
      chronological-aged cells grown under glucose restriction displayed lowered levels
      of lipid peroxidation product lipofuscin. Intracellular iron concentration is
      kept almost unchanged, whereas in non-restricted cells, the values increase up 4
      5 times. The pro-oxidant effects of such increased iron concentration would
      account for the damage observed. Also, calorie-restricted cells show undamaged
      catalase, which clearly appears carbonylated in cells grown at a high glucose
      concentration. These results may explain lengthening of the viability of
      chronological-aged cells and could have an important role in replicative life
      span extension by calorie restriction.

PMID- 15166232
TI  - Conformational regulation of alpha 4 beta 1-integrin affinity by reducing agents.
      "Inside-out" signaling is independent of and additive to reduction-regulated
      integrin activation.
AB  - The alpha(4)beta(1)-integrin (very late antigen-4 (VLA-4), CD49d/CD29) is an
      adhesion receptor involved in the interaction of lymphocytes, dendritic cells,
      and stem cells with the extracellular matrix and endothelial cells. This and
      other integrins have the ability to regulate their affinity for ligands through a
      process termed "inside-out" signaling that affects cell adhesion avidity. Several
      mechanisms are known to regulate integrin affinity and conformation:
      conformational changes induced by separation of the C-terminal tails, divalent
      ions, and reducing agents. Recently, we described a fluorescent LDV-containing
      small molecule that was used to monitor VLA-4 affinity changes in live cells
      (Chigaev, A., Blenc, A. M., Braaten, J. V., Kumaraswamy, N., Kepley, C. L.,
      Andrews, R. P., Oliver, J. M., Edwards, B. S., Prossnitz, E. R., Larson, R. S.,
      and Sklar, L. A. (2001) J. Biol. Chem. 276, 48670-48678). Using the same
      molecule, we also developed a fluorescence resonance energy transfer-based assay
      to probe the "switchblade-like" opening of VLA-4 upon activation. Here, we
      investigated the effect of reducing agents on the affinity and conformational
      state of the VLA-4 integrin simultaneously with cell activation initiated by
      inside-out signaling through G protein-coupled receptors or Mn(2+) in live cells
      in real time. We found that reducing agents (dithiothreitol and 2,3-dimercapto-1
      propanesulfonic acid) induced multiple states of high affinity of VLA-4, where
      the affinity change was accompanied by an extension of the integrin molecule.
      Bacitracin, an inhibitor of the reductive function of the plasma membrane,
      diminished the effect of dithiothreitol, but had no effect on inside-out
      signaling. Based on this result and differences in the kinetics of integrin
      activation, we conclude that conformational activation of VLA-4 by inside-out
      signaling is independent of and additive to reduction-regulated integrin
      activation.

PMID- 15166234
TI  - The biotin connection: Severo Ochoa, Harland Wood, and Feodor Lynen.

PMID- 15166235
TI  - DNA damage-induced Def1-RNA polymerase II interaction and Def1 requirement for
      polymerase ubiquitylation in vitro.
AB  - UV-induced DNA damage results in ubiquitylation and degradation of RNA polymerase
      II (RNAPII). In yeast, this requires the DEF1 gene, the product of which forms a
      complex with the transcription-coupling repair factor, Rad26. However, whether
      Def1 is directly involved in RNAPII ubiquitylation has remained unclear. Here we
      report the establishment of a reconstituted system for studying UV-induced RNAPII
      ubiquitylation, which mimics the known requirements for this process in vitro.
      Using this system, we show that Def1 is indeed directly required for RNAPII
      ubiquitylation. Moreover, Def1 interacts with RNAPII in a damage-dependent
      manner. These results support a model in which Def1 interacts with RNAPII in
      response to DNA damage, recruiting the ubiquitylation machinery to enable its
      modification and subsequent degradation.

PMID- 15166236
TI  - The brain-specific double-stranded RNA-binding protein Staufen2: nucleolar
      accumulation and isoform-specific exportin-5-dependent export.
AB  - The mammalian double-stranded RNA-binding proteins Staufen (Stau1 and Stau2) are
      involved in RNA localization in polarized neurons. In contrast to the more
      ubiquitously expressed Stau1, Stau2 is mainly expressed in the nervous system. In
      Drosophila, the third double-stranded RNA-binding domain (RBD3) of Staufen is
      essential for RNA interaction. When conserved amino acids within the RBD3 of
      Stau2 were mutated to render Stau2 defective for RNA binding, the mutant Stau2
      proteins accumulate predominantly in the nucleolus. This is in contrast to wild
      type Stau2 that mostly localizes in the cytosol. The nuclear import is dependent
      on a nuclear localization signal in close proximity to the RBD3. The nuclear
      export of Stau2 is not dependent on CRM1 but rather on Exportin-5. We show that
      Exportin-5 interacts with the RBD3 of wild type Stau2 in an RNA-dependent manner
      in vitro but not with mutant Stau2. When Exportin-5 is down-regulated by RNA
      interference, only the largest isoform of Stau2 (Stau2(62)) preferentially
      accumulates in the nucleolus. It is tempting to speculate that Stau2(62) binds
      RNA in the nucleus and assembles into ribonucleoparticles, which are then
      exported via the Exportin-5 pathway to their final destination.

PMID- 15166237
TI  - The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for
      recombinant N-type (Cav2.2) calcium channels.
AB  - The omega-conotoxins from fish-hunting cone snails are potent inhibitors of
      voltage-gated calcium channels. The omega-conotoxins MVIIA and CVID are selective
      N-type calcium channel inhibitors with potential in the treatment of chronic
      pain. The beta and alpha(2)delta-1 auxiliary subunits influence the expression
      and characteristics of the alpha(1B) subunit of N-type channels and are
      differentially regulated in disease states, including pain. In this study, we
      examined the influence of these auxiliary subunits on the ability of the omega
      conotoxins GVIA, MVIIA, CVID and analogues to inhibit peripheral and central
      forms of the rat N-type channels. Although the beta3 subunit had little influence
      on the on- and off-rates of omega-conotoxins, coexpression of alpha(2)delta with
      alpha(1B) significantly reduced on-rates and equilibrium inhibition at both the
      central and peripheral isoforms of the N-type channels. The alpha(2)delta also
      enhanced the selectivity of MVIIA, but not CVID, for the central isoform. Similar
      but less pronounced trends were also observed for N-type channels expressed in
      human embryonic kidney cells. The influence of alpha(2)delta was not affected by
      oocyte deglycosylation. The extent of recovery from the omega-conotoxin block was
      least for GVIA, intermediate for MVIIA, and almost complete for CVID. Application
      of a hyperpolarizing holding potential (-120 mV) did not significantly enhance
      the extent of CVID recovery. Interestingly, [R10K]MVIIA and [O10K]GVIA had
      greater recovery from the block, whereas [K10R]CVID had reduced recovery from the
      block, indicating that position 10 had an important influence on the extent of
      omega-conotoxin reversibility. Recovery from CVID block was reduced in the
      presence of alpha(2)delta in human embryonic kidney cells and in oocytes
      expressing alpha(1B-b). These results may have implications for the
      antinociceptive properties of omega-conotoxins, given that the alpha(2)delta
      subunit is up-regulated in certain pain states.

PMID- 15166238
TI  - Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in
      regulating fibroblast survival in response to contraction of type I collagen
      matrices via a beta 1 integrin viability signaling pathway.
AB  - The beta(1) integrin, functioning as a mechanoreceptor, senses a mechanical
      stimulus generated during collagen matrix contraction and down-regulates the
      phosphatidylinositol 3-kinase (PI3K)/Akt survival signal triggering apoptosis.
      The identities of integrin-associated signal molecules in the focal adhesion
      complex that are responsible for propagating beta(1) integrin viability signals
      in response to collagen matrix contraction are not known. Here we show that in
      response to collagen contraction focal adhesion kinase (FAK) is dephosphorylated.
      In contrast, enforced activation of beta(1) integrin by anti-beta(1) integrin
      antibody, which protects fibroblasts from apoptosis, preserves FAK
      phosphorylation. We demonstrate that ligation of beta(1) integrin by type I
      collagen or by enforced activation of beta(1) integrin by antibody promotes
      phosphorylation of FAK, p85 subunit of PI3K, and serine 473 of Akt. Wortmannin
      inhibited Akt but not FAK phosphorylation in response to enforced activation of
      beta(1) integrin by antibody. Blocking FAK by pharmacologic inhibition or by
      dominant negative FAK attenuated phosphorylation of p85 subunit of PI3K and Akt.
      Dominant negative FAK augmented fibroblast apoptosis during collagen contraction,
      and this was associated with diminished Akt activity. Constitutively active FAK
      augmented levels of p85 subunit of PI3K and Akt phosphorylation, and fibroblasts
      were protected from apoptosis. Our data identify a novel role for FAK,
      functioning upstream of PI3K/Akt, in transducing a beta(1) integrin viability
      signal in collagen matrices.

PMID- 15166239
TI  - Syk-mediated tyrosine phosphorylation is required for the association of
      hematopoietic lineage cell-specific protein 1 with lipid rafts and B cell antigen
      receptor signalosome complex.
AB  - Hematopoietic lineage cell-specific protein 1 (HS1) is an F-actin- and actin
      related proteins 2 and 3 (Arp2/3)-binding protein that undergoes a rapid tyrosine
      phosphorylation upon B cell antigen receptor (BCR) activation. Density gradient
      centrifugation of Triton X-100 lysates from B lymphocytes demonstrated that HS1
      was translocated in response to BCR cross-linking into lipid raft microdomain
      along with Arp2/3 complex and Wiskott-Aldrich syndrome protein. HS1-green
      fluorescent protein was localized in membrane patches enriched with GM1
      gangliosides and BCR in the cells treated with anti-IgM antibody. Colocalization
      of HS1-green fluorescent protein with BCR was also correlated with tyrosine
      phosphorylation of HS1. Interestingly a murine HS1 mutant at the tyrosine
      residues Tyr388 and Tyr405 targeted by Syk failed to respond to BCR cross-linking
      for either translocation into lipid rafts or colocalization with BCR within
      cells. Furthermore HS1 was unable to translocate into lipid rafts in a chicken B
      cell line deficient in Syk. Reintroducing a Syk construct into the Syk knock-out
      cells recovered effectively both tyrosine phosphorylation and translocation of
      HS1 into lipid rafts. In contrast, translocation of HS1 into rafts was normal in
      a Lyn knock-out B cell line, and an HS1 mutant at the tyrosine residue Tyr222
      targeted by Lyn maintained the ability to partition into rafts upon BCR cross
      linking. These data indicate that Syk plays an important role in the
      translocation of HS1 into lipid rafts and may be responsible for actin assembly
      recruitment to rafts and subsequent antigen presentations.

PMID- 15166240
TI  - Interactions of Arabidopsis RS domain containing cyclophilins with SR proteins
      and U1 and U11 small nuclear ribonucleoprotein-specific proteins suggest their
      involvement in pre-mRNA Splicing.
AB  - Ser/Arg (SR)-rich proteins are important splicing factors in both general and
      alternative splicing. By binding to specific sequences on pre-mRNA and
      interacting with other splicing factors via their RS domain they mediate
      different intraspliceosomal contacts, thereby helping in splice site selection
      and spliceosome assembly. While characterizing new members of this protein family
      in Arabidopsis, we have identified two proteins, termed CypRS64 and CypRS92,
      consisting of an N-terminal peptidyl-prolyl cis/trans isomerase domain and a C
      terminal domain with many SR/SP dipeptides. Cyclophilins possess a peptidyl
      prolyl cis/trans isomerase activity and are implicated in protein folding,
      assembly, and transport. CypRS64 interacts in vivo and in vitro with a subset of
      Arabidopsis SR proteins, including SRp30 and SRp34/SR1, two homologs of mammalian
      SF2/ASF, known to be important for 5' splice site recognition. In addition, both
      cyclophilins interact with U1-70K and U11-35K, which in turn are binding partners
      of SRp34/SR1. CypRS64 is a nucleoplasmic protein, but in most cells expressing
      CypRS64-GFP fusion it was also found in one to six round nuclear bodies. However,
      co-expression of CypRS64 with its binding partners resulted in re-localization of
      CypRS64 from the nuclear bodies to nuclear speckles, indicating functional
      interactions. These findings together with the observation that binding of
      SRp34/SR1 to CypRS64 is phosphorylation-dependent indicate an involvement of
      CypRS64 in nuclear pre-mRNA splicing, possibly by regulating
      phosphorylation/dephosphorylation of SR proteins and other spliceosomal
      components. Alternatively, binding of CypRS64 to proteins important for 5' splice
      site recognition suggests its involvement in the dynamics of spliceosome
      assembly.

PMID- 15166241
TI  - SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in
      platelets.
AB  - Integrin alpha(IIb)beta(3) plays a critical role in platelet function, promoting
      a broad range of functional responses including platelet adhesion, spreading,
      aggregation, clot retraction, and platelet procoagulant function. Signaling
      events operating downstream of this receptor (outside-in signaling) are important
      for these responses; however the mechanisms negatively regulating integrin
      alpha(IIb)beta(3) signaling remain ill-defined. We demonstrate here a major role
      for the Src homology 2 domain-containing inositol 5-phosphatase (SHIP1) and Src
      family kinase, Lyn, in this process. Our studies on murine SHIP1 knockout
      platelets have defined a major role for this enzyme in regulating integrin
      alpha(IIb)beta(3)-dependent phosphatidylinositol 3,4,5-trisphosphate
      (PtdIns(3,4,5)P(3)) accumulation, necessary for a cytosolic calcium response and
      platelet spreading. SHIP1 phosphorylation and PtdIns(3,4,5)P(3) metabolism is
      partially regulated through Lyn kinase, resulting in an enhanced calcium flux and
      spreading response in Lyn-deficient mouse platelets. Analysis of platelet
      adhesion dynamics under physiological blood flow conditions revealed an important
      role for SHIP1 in regulating platelet adhesion on fibrinogen. Specifically, SHIP1
      dependent PtdIns(3,4,5)P(3) metabolism down-regulates the stability of integrin
      alpha(IIb)beta(3)-fibrinogen adhesive bonds, leading to a decrease in the
      proportion of platelets forming shear-resistant adhesion contacts. These studies
      define a major role for SHIP1 and Lyn as negative regulators of integrin
      alpha(IIb)beta(3) adhesive and signaling function.

PMID- 15166242
TI  - Mitochondrial ATP synthasome: three-dimensional structure by electron microscopy
      of the ATP synthase in complex formation with carriers for Pi and ADP/ATP.
AB  - The terminal steps involved in making ATP in mitochondria require an ATP synthase
      (F(0)F(1)) comprised of two motors, a phosphate carrier (PIC), and an adenine
      nucleotide carrier (ANC). Under mild conditions, these entities sub-fractionate
      as an ATP synthase/PIC/ANC complex or "ATP synthasome" (Ko, Y.H., Delannoy, M,
      Hullihen, J., Chiu, W., and Pedersen, P.L. (2003) J. Biol. Chem. 278, 12305
      12309). As a first step toward obtaining three-dimensional information about this
      large complex or "metabolon" and the locations of PIC and ANC therein, we
      dispersed ATP synthasomes into single complexes and visualized negatively stained
      images by electron microscopy (EM) that showed clearly the classical headpiece,
      central stalk, and basepiece. Parallel immuno-EM studies revealed the presence of
      PIC and ANC located non-centrally in the basepiece, and other studies implicated
      an ATP synthase/PIC/ANC stoichiometry near 1:1:1. Single ATP synthasome images
      (7506) were boxed, and, using EMAN software, a three-dimensional model was
      obtained at a resolution of 23 A. Significantly, the basepiece is oblong and
      contains two domains, the larger of which connects to the central stalk, whereas
      the smaller appears as an extension. Docking studies with known structures
      together with the immuno-EM studies suggest that PIC or ANC may be located in the
      smaller domain, whereas the other transporter resides nearby in the larger
      domain. Collectively, these finding support a mechanism in which the entry of the
      substrates ADP and P(i) into mitochondria, the synthesis of ATP on F(1), and the
      release and exit of ATP are very localized and highly coordinated events.

PMID- 15166243
TI  - In situ respiration and bioenergetic status of mitochondria in primary cerebellar
      granule neuronal cultures exposed continuously to glutamate.
AB  - Mitochondria play a central role in neuronal death during pathological exposure
      to glutamate (excitotoxicity). To investigate the detailed bioenergetics of the
      in situ mitochondria, a method is described to monitor continuously the
      respiration of primary cerebellar granule neuron cultures while simultaneously
      imaging cytoplasmic Ca(2+) and mitochondrial membrane potential. Coverslip
      attached cells were perfused in an imaging chamber with upstream and downstream
      flow-through oxygen electrodes. The bioenergetic consequences of chronic
      glutamate exposure were investigated, including ATP supply and demand, proton
      leak, and mitochondrial respiratory capacity during chronic glutamate exposure.
      In 25 mM K(+) medium supplemented with 10% dialyzed serum, cells utilized 54% of
      their respiratory capacity in the absence of receptor activation (37% for ATP
      generation, 12% to drive the mitochondrial proton leak, and the residual 5% was
      nonmitochondrial). glutamate initially increased mitochondrial respiration from
      51 to 68% of capacity, followed by a slow decline. It was estimated that 85% of
      this increased respiration was because of increased ATP demand, whereas 15% was
      attributable to a transient mitochondrial proton leak. N-Methyl-D-aspartate
      receptor activation was only responsible for 62% of the increased respiration.
      When adjusted for cell death over 3 h of glutamate exposure, respiration of the
      viable cells remained near basal and protonophore stimulated respiration to the
      same extent as control cells. Pyruvate-supplemented media protected cells from
      glutamate excitotoxicity, although this was associated with mitochondrial
      dysfunction. We conclude that excitotoxicity under these conditions is not
      because of an ATP deficit or uncoupling. Furthermore, mitochondria maintain the
      same respiratory capacity as in control cells.

PMID- 15166244
TI  - Extracellular oxidation by taurine chloramine activates ERK via the epidermal
      growth factor receptor.
AB  - Taurine is present in high concentrations in neutrophils, and when the cells are
      stimulated taurine can react with hypochlorous acid (HOCl) to form taurine
      chloramine (Tau-Cl). This compound retains oxidant activity and can affect the
      neutrophil itself or surrounding tissue cells. We have investigated the effects
      of Tau-Cl on MAPK signaling in human umbilical vein endothelial cells (HUVEC).
      Tau-Cl caused no loss in intracellular glutathione or inactivation of the thiol
      sensitive enzyme glyceraldehyde-3-phosphate dehydrogenase, indicating that it had
      not entered the cells. However, stimulation of HUVEC with Tau-Cl (20-100 microM)
      induced the rapid activation of ERK within 10 min. This activation was abolished
      by inhibition of MEK by U0126, indicating that it was not because of direct
      oxidation of ERK. No activation of p38 was detected. These results suggest that
      Tau-Cl reacts with a cell membrane target that results in intracellular ERK
      activation. Tau-Cl over the same concentration range and time scale stimulated
      epidermal growth factor (EGF) receptor tyrosine phosphorylation in A431 cells and
      HUVEC. The EGF receptor inhibitor PD158780 significantly attenuated Tau-Cl
      induced phosphorylation of both the EGF receptor and ERK. This implicates the EGF
      receptor in the upstream activation of ERK. The Src tyrosine kinase inhibitor 4
      amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine had no effect on
      Tau-Cl-induced EGF receptor or ERK activation. We propose that Tau-Cl acts on an
      oxidant-sensitive target on the cell surface, this being either the EGF receptor
      itself or another target that can interact with the EGF receptor, with
      consequential activation of ERK.

PMID- 15166245
TI  - C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C
      virus pseudotype particles.
AB  - The molecular mechanisms involved in the hepatic tropism of hepatitis C virus
      (HCV) have not been identified. We have shown previously that liver-expressed C
      type lectins L-SIGN and DC-SIGN bind the HCV E2 glycoprotein with high affinity
      (Lozach, P. Y., Lortat-Jacob, H., de Lacroix de Lavalette, A., Staropoli, I.,
      Foung, S., Amara, A., Houles, C., Fieschi, F., Schwartz, O., Virelizier, J. L.,
      Arenzana-Seisdedos, F., and Altmeyer, R. (2003) J. Biol. Chem. 278, 20358-20366).
      To analyze the functional relevance of this interaction, we generated pseudotyped
      lentivirus particles presenting HCV glycoproteins E1 and E2 at the virion surface
      (HCV-pp). High mannose N-glycans are present on E1 and, to a lesser extent, on E2
      proteins of mature infectious HCV-pp. Such particles bind to both L-SIGN and DC
      SIGN, but they cannot use these receptors for entry into cells. However,
      infectious virus is transmitted efficiently when permissive Huh-7 cells are
      cocultured with HCV-pp bound to L-SIGN or to DC-SIGN-positive cell lines. HCV-pp
      transmission via L-SIGN or DC-SIGN is inhibited by characteristic inhibitors such
      as the calcium chelator EGTA and monoclonal antibodies directed against lectin
      carbohydrate recognition domains of both lectins. In support of the biological
      relevance of this phenomenon, dendritic cells expressing endogenous DC-SIGN
      transmitted HCV-pp with high efficiency in a DC-SIGN-dependent manner. Our
      results support the hypothesis that C-type lectins such as the liver sinusoidal
      endothelial cell-expressed L-SIGN could act as a capture receptor for HCV in the
      liver and transmit infectious virions to neighboring hepatocytes.

PMID- 15166246
TI  - Tuning a nitrate reductase for function. The first spectropotentiometric
      characterization of a bacterial assimilatory nitrate reductase reveals novel
      redox properties.
AB  - Bacterial cytoplasmic assimilatory nitrate reductases are the least well
      characterized of all of the subgroups of nitrate reductases. In the present study
      the ferredoxin-dependent nitrate reductase NarB of the cyanobacterium
      Synechococcus sp. PCC 7942 was analyzed by spectropotentiometry and protein film
      voltammetry. Metal and acid-labile sulfide analysis revealed nearest integer
      values of 4:4:1 (iron/sulfur/molybdenum)/molecule of NarB. Analysis of dithionite
      reduced enzyme by low temperature EPR revealed at 10 K the presence of a signal
      that is characteristic of a [4Fe-4S](1+) cluster. EPR-monitored potentiometric
      titration of NarB revealed that this cluster titrated as an n = 1 Nernstian
      component with a midpoint redox potential (E(m)) of -190 mV. EPR spectra
      collected at 60 K revealed a Mo(V) signal termed "very high g" with g(av) =
      2.0047 in air-oxidized enzyme that accounted for only 10-20% of the total
      molybdenum. This signal disappeared upon reduction with dithionite, and a new
      "high g" species (g(av) = 1.9897) was observed. In potentiometric titrations the
      high g Mo(V) signal developed over the potential range of -100 to -350 mV (E(m)
      Mo(6+/5+) = -150 mV), and when fully developed, it accounted for 1 mol of
      Mo(V)/mol of enzyme. Protein film voltammetry of NarB revealed that activity is
      turned on at potentials below -200 mV, where the cofactors are predominantly [4Fe
      4S](1+) and Mo(5+). The data suggests that during the catalytic cycle nitrate
      will bind to the Mo(5+) state of NarB in which the enzyme is minimally two
      electron-reduced. Comparison of the spectral properties of NarB with those of the
      membrane-bound and periplasmic respiratory nitrate reductases reveals that it is
      closely related to the periplasmic enzyme, but the potential of the molybdenum
      center of NarB is tuned to operate at lower potentials, consistent with the
      coupling of NarB to low potential ferredoxins in the cell cytoplasm.

PMID- 15166247
TI  - Association of the breast cancer protein MLN51 with the exon junction complex via
      its speckle localizer and RNA binding module.
AB  - MLN51 is a nucleocytoplasmic shuttling protein that is overexpressed in breast
      cancer. The function of MLN51 in mammals remains elusive. Its fly homolog, named
      barentsz, as well as the proteins mago nashi and tsunagi have been shown to be
      required for proper oskar mRNA localization to the posterior pole of the oocyte.
      Magoh and Y14, the human homologs of mago nashi and tsunagi, are core components
      of the exon junction complex (EJC). The EJC is assembled on spliced mRNAs and
      plays important roles in post-splicing events including mRNA export, nonsense
      mediated mRNA decay, and translation. In the present study, we show that human
      MLN51 is an RNA-binding protein present in ribonucleo-protein complexes. By co
      immunoprecipitation assays, endogenous MLN51 protein is found to be associated
      with EJC components, including Magoh, Y14, and NFX1/TAP, and subcellular
      localization studies indicate that MLN51 transiently co-localizes with Magoh in
      nuclear speckles. Moreover, we demonstrate that MLN51 specifically associates
      with spliced mRNAs in co-precipitation experiments, both in the nucleus and in
      the cytoplasm, at the position where the EJC is deposited. Most interesting, we
      have identified a region within MLN51 sufficient to bind RNA, to interact with
      Magoh and spliced mRNA, and to address the protein to nuclear speckles. This
      conserved region of MLN51 was therefore named SELOR for speckle localizer and RNA
      binding module. Altogether our data demonstrate that MLN51 associates with EJC in
      the nucleus and remains stably associated with mRNA in the cytoplasm, suggesting
      that its overexpression might alter mRNA metabolism in cancer.

PMID- 15166248
TI  - Glycoprotein hormone assembly in the endoplasmic reticulum: IV. Probable
      mechanism of subunit docking and completion of assembly.
AB  - The unique structures of human choriogonadotropin (hCG) and related glycoprotein
      hormones make them well suited for studies of protein folding in the endoplasmic
      reticulum. hCG is stabilized by a strand of its beta-subunit that has been
      likened to a "seatbelt" because it surrounds alpha-subunit loop 2 and its end is
      "latched" by an intrasubunit disulfide bond to the beta-subunit core. As shown
      here, assembly begins when parts of the NH(2) terminus, cysteine knot, and loops
      1 and 3 of the alpha-subunit dock reversibly with parts of the NH(2) terminus,
      cystine knot, and loop 2 of the hCG beta-subunit. Whereas the seatbelt can
      contribute to the stability of the docked subunit complex, it interferes with
      docking and/or destabilizes the docked complex when it is unlatched. This
      explains why most hCG is assembled by threading the glycosylated end of alpha
      subunit loop 2 beneath the latched seatbelt rather than by wrapping the unlatched
      seatbelt around this loop. hCG assembly appears to be limited by the need to
      disrupt the disulfide that stabilizes the small seatbelt loop prior to threading.
      We postulate that assembly depends on a "zipper-like" sequential formation of
      intersubunit and intrasubunit hydrogen bonds between backbone atoms of several
      residues in the beta-subunit cystine knot, alpha-subunit loop 2, and the small
      seatbelt loop. The resulting intersubunit beta-sheet enhances the stability of
      the seatbelt loop disulfide, which shortens the seatbelt and secures the
      heterodimer. Formation of this disulfide also explains the ability of the
      seatbelt loop to facilitate latching during assembly by the wraparound pathway.

PMID- 15166249
TI  - Cyclic AMP modulates the functional plasticity of immature dendritic cells by
      inhibiting Src-like kinases through protein kinase A-mediated signaling.
AB  - Immature dendritic cells (iDCs) can be instructed to polarize the immune response
      toward a noninflammatory pathway by mediators that increase the intracellular
      concentration of cAMP. This phenomenon is associated with the ability of the
      cyclic nucleoside to inhibit the release of pro-inflammatory cytokines without
      affecting the differentiation process of the dendritic cells (DCs). Here we
      investigated the ability of cAMP to modulate the endotoxin signaling by exposing
      DCs to exogenous 8-bromium-cyclic AMP in the presence or absence of H89, a
      selective inhibitor of the protein kinase A, one of the major molecular targets
      of the cyclic nucleoside. cAMP affects the early lipopolysaccharide-induced
      signaling cascade dissociating the activation of NF-kappa B, p38, and ERK
      pathways from the stimulation of c-Src and Lyn kinases. This phenomenon was
      prevented by H89. The pharmacological block of Src-like tyrosine kinases induces
      comparable results confirming the involvement of this family of enzymes in the
      mechanism controlling the release of cytokines in human monocyte-derived iDCs. We
      propose that the cAMP-protein kinase A-dependent pathway regulates the functional
      plasticity of iDCs by gating the Toll-like receptor signaling at the level of Src
      like kinases.

PMID- 15166250
TI  - Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid
      rafts, a process that requires porcupine.
AB  - Wnt signaling pathways regulate many developmental responses; however, little is
      known about how Wnt ligands function on a biochemical level. Recent studies have
      shown that Wnt-3a is palmitoylated before secretion. Here we report that
      Drosophila Wnt-1 (Wingless) also undergoes a lipid modification. Lipidation
      occurs in the endoplasmic reticulum and is dependent on Porcupine, a putative O
      acyltransferase. After modification, DWnt-1 partitions as a membrane-anchored
      protein and is sorted into lipid raft detergent-insoluble microdomains.
      Lipidation, raft targeting, and secretion can be blocked by the addition of 2
      bromopalmitate, a competitive inhibitor of O-acyltransferase activity. Based on
      these results we propose a model whereby lipidation targets Wnt-1 to secretory
      vesicles that deliver the ligand to specialized microdomains at the cell surface
      where it can be packaged for secretion.

PMID- 15166251
TI  - Glucose regulation of insulin gene expression requires the recruitment of p300 by
      the beta-cell-specific transcription factor Pdx-1.
AB  - Regulation of insulin gene expression in response to increases in blood glucose
      levels is essential for maintaining normal glucose homeostasis; however, the
      exact mechanisms by which glucose stimulates insulin gene transcription are not
      known. We have shown previously that glucose stimulates insulin gene expression
      by causing the hyperacetylation of histone H4 at the insulin promoter. We
      demonstrate that the histone acetyltransferase p300 is recruited to the insulin
      promoter only at high concentrations of glucose via its interaction with the beta
      cell-specific transcription factor Pdx-1. Disruption of the function of the
      endogenous Pdx-1 abolishes the recruitment of p300 to the insulin gene promoter
      at high concentrations of glucose and results in decreased histone H4 acetylation
      and insulin gene expression. Furthermore, we demonstrate that the glucose
      dependent interaction of Pdx-1 with p300 is regulated by a phosphorylation event
      that changes the localization of Pdx-1. Based on these data, we conclude that
      hyperacetylation of histone H4 at the insulin gene promoter in response to high
      concentrations of glucose depends on the beta-cell-specific transcription factor
      Pdx-1, which is required for the recruitment of the histone acetyltransferase
      p300 to the insulin gene promoter.

PMID- 15166252
TI  - Modulation of ligand selectivity associated with activation of the transmembrane
      region of the human follitropin receptor.
AB  - Recently, three naturally occurring mutations in the serpentine region of the FSH
      receptor (FSHr) (D567N and T449I/A) have been identified in three families with
      spontaneous ovarian hyperstimulation syndrome (OHSS). All mutant receptors
      displayed abnormally high sensitivity to human chorionic gonadotropin and, in
      addition, D567N and T449A displayed concomitant increase in sensitivity to TSH
      and detectable constitutive activity. In the present study, we have used a
      combination of site-directed mutagenesis experiments and molecular modeling to
      explore the mechanisms responsible for the phenotype of the three OHSS FSHr
      mutants. Our results suggest that all mutations lead to weakening of interhelical
      locks between transmembrane helix (TM)-VI and TM-III, or TM-VI and TM-VII, which
      contributes to maintaining the receptor in the inactive state. They also indicate
      that broadening of the functional specificity of the mutant FSHr constructs is
      correlated to their increase in constitutive activity. This relation between
      basal activity and functional specificity is a characteristic of the FSHr, which
      is not shared by the other glycoprotein hormone receptors. It leads to the
      interesting suggestion that different pathways have been followed during primate
      evolution to avoid promiscuous stimulation of the TSHr and FSHr by human
      chorionic gonadotropin. In the hFSHr, specificity would be exerted both by the
      ectodomain and the serpentine portion.

PMID- 15166253
TI  - Functional rescue of the constitutively internalized V2 vasopressin receptor
      mutant R137H by the pharmacological chaperone action of SR49059.
AB  - In most cases, nephrogenic diabetes insipidus results from mutations in the V2
      vasopressin receptor (V2R) gene that cause intracellular retention of improperly
      folded receptors. We previously reported that cell permeable V2R antagonists act
      as pharmacological chaperones that rescue folding, trafficking, and function of
      several V2R mutants. More recently, the vasopressin antagonist, SR49059, was
      found to be therapeutically active in nephrogenic diabetes insipidus patients.
      Three of the patients with positive responses harbored the mutation R137H,
      previously reported to lead to constitutive endocytosis. This raises the
      possibility that, instead of acting as a pharmacological chaperone by favoring
      proper maturation of the receptors, SR49059 could mediate its action on R137H V2R
      by preventing its endocytosis. Here we report that the beta-arrestin-mediated
      constitutive endocytosis of R137H V2R is not affected by SR49059, indicating that
      the functional rescue observed does not result from a stabilization of the
      receptor at the cell surface. Moreover, metabolic labeling revealed that R137H
      V2R is also poorly processed to the mature form. SR49059 treatment significantly
      improved its maturation and cell surface targeting, indicating that the
      functional rescue of R137H V2Rs results from the pharmacological chaperone action
      of the antagonist.

PMID- 15166254
TI  - Thyrotropin and serum regulate thyroid cell proliferation through differential
      effects on p27 expression and localization.
AB  - Thyroid cell proliferation is regulated by the concerted action of TSH/cAMP and
      serum growth factors. The specific contributions of cAMP-dependent vs. 
      independent signals to cell cycle progression are not well understood. We
      examined the molecular basis for the synergistic effects of TSH and serum on G1/S
      phase cell cycle progression in rat thyroid cells. Although strictly required for
      thyroid cell proliferation, TSH failed to stimulate G1 phase cell cycle
      progression. Together with serum, TSH increased the number of cycling cells. TSH
      enhanced the effects of serum on retinoblastoma protein hyperphosphorylation,
      cyclin-dependent kinase 2 activity, and cyclin A expression. Most notably, TSH
      and serum elicited strikingly different effects on p27 localization. TSH
      stimulated the nuclear accumulation of p27, whereas serum induced its nuclear
      export. Unexpectedly, TSH enhanced the depletion of nuclear p27 in serum-treated
      cells. Furthermore, only combined treatment with TSH and serum led to rapamycin
      sensitive p27 turnover. Together, TSH and serum stimulated p70S6K activity that
      remained high through S phase. These data suggest that TSH regulates cell cycle
      progression, in part, by increasing the number of cycling cells through p70S6K
      mediated effects on the localization of p27.

PMID- 15166255
TI  - Enhanced cAMP protein kinase A signaling determines improved insulin secretion in
      a clonal insulin-producing beta-cell line (INS-1 832/13).
AB  - In type 2 diabetes, beta-cells become glucose unresponsive, contributing to
      hyperglycemia. To address this problem, we recently created clonal insulin
      producing cell lines from the INS-1 insulinoma line, which exhibit glucose
      responsiveness ranging from poor to robust. Here, mechanisms that determine
      secretory performance were identified by functionally comparing glucose
      responsive 832/13 beta-cells with glucose-unresponsive 832/2 beta-cells. Thus,
      insulin secretion from 832/13 cells maximally rose 8-fold in response to glucose,
      whereas 832/2 cells responded only 1.5-fold. Insulin content in both lines was
      similar, indicating that differences in stimulus-secretion coupling account for
      the differential secretory performance. Forskolin or isobutylmethylxanthine
      markedly enhanced insulin secretion from 832/13 but not from 832/2 cells,
      suggesting that cAMP is essential for the enhanced secretory performance of
      832/13 cells. Indeed, 8-bromoadenosine-3',5'-cyclic monophosphorothioate, rp
      isomer (Rp-8-Br-cAMPS) an inhibitor of protein kinase A (PKA), inhibited insulin
      secretion in response to glucose with or without forskolin. Interestingly,
      whereas forskolin markedly increased cAMP in 832/2 cells, 832/13 cells exhibited
      only a marginal rise in cAMP. This suggests that 832/13 cells are more sensitive
      to cAMP. Indeed, the cAMP-induced exocytotic response in patch-clamped 832/13
      cells was 2-fold greater than in 832/2 cells. Furthermore, immunoblotting
      revealed that expression of the catalytic subunit of PKA was 2-fold higher in
      832/13 cells. Moreover, when the regulatory subunit of PKA was overexpressed in
      832/13 cells, to reduce the level of unbound and catalytically active kinase,
      insulin secretion and PKA activity were blunted. Our findings show that cAMP-PKA
      signaling correlates with secretory performance in beta-cells.

PMID- 15166256
TI  - Fenofibrate impairs rat mitochondrial function by inhibition of respiratory
      complex I.
AB  - Fibrates are used for the treatment of dyslipidemia and known to affect
      mitochondrial function in vitro. To better understand the mechanisms underlying
      their mitochondrial effects, fibrate actions on complex I of the respiratory
      chain and cell respiration were studied in vitro. In homogenates of rat skeletal
      muscle, fenofibrate, and to a lesser extent clofibrate, reduced the activity of
      complex I (10, 30, and 100 microM fenofibrate: -41 +/- 7%, -70 +/- 2%, and -78 +/
      4%; 100 microM clofibrate: -27 +/- 7%; p < 0.005 each). Inhibition of complex I
      by fenofibrate (100 microM) was confirmed by reduced state 3 respiration of
      isolated mitochondria consuming glutamate + malate as substrates for complex I (
      33 +/- 4%; p < 0.0005), but not of such consuming succinate as substrate for
      complex II (-8 +/- 4%; NS). In isolated rat muscle, 24-h fenofibrate exposure
      (25, 50, and 100 microM) decreased CO(2) production from palmitate (-15 +/- 7%, 
      23 +/- 8%, and -22 +/- 7%; p < 0.05 each) and increased lactate release (+15 +/-
      5%, +14 +/- 5%, and + 17 +/- 6%; p < 0.02 each) indicating impaired cell
      respiration. Ciprofibrate and gemfibrocil (but not bezafibrate) impaired cell
      respiration without any inhibition of complex I. Our findings support the notion
      that individual fibrates induce mitochondrial dysfunction via different molecular
      mechanisms and show that fenofibrate predominantly acts by inhibition of complex
      I of the respiratory chain.

PMID- 15166257
TI  - Antinociceptive structure-activity studies with enkephalin-based opioid
      glycopeptides.
AB  - Development of opioid peptides as therapeutic agents has historically been
      limited due to pharmacokinetic issues including stability and blood-brain barrier
      (BBB) permeability. Glycosylation of opioid peptides can increase peptide serum
      stability and BBB penetration. To further define the requirements for optimizing
      in vivo antinociceptive potency following intravenous administration, we
      synthesized a series of enkephalin-based glycopeptides using solid phase 9
      fluorenylmethyloxy carbamate methods. The compounds differed in the sixth and
      subsequent amino acid residues (Ser or Thr) and in the attached carbohydrate
      moiety. In vitro binding and functional smooth muscle bioassays indicated that
      the addition of mono- or disaccharides did not significantly affect the opioid
      receptor affinity or agonist activity of the glycopeptides compared with their
      unglycosylated parent peptides. All of the glycopeptides tested produced potent
      antinociceptive effects in male ICR mice following intracerebroventricular
      injection in the 55 degrees C tail-flick test. The calculated A(50) values for
      the Ser/Thr and monosaccharide combinations were all very similar with values
      ranging from 0.02 to 0.09 nmol. Selected compounds were administered to mice
      intravenously and tested for antinociception to indirectly assess serum stability
      and BBB penetration. All compounds tested produced full antinociceptive effects
      with calculated A (50) values ranging from 2.2 to 46.4 micromol/kg with the
      disaccharides having potencies that equaled or exceeded that of morphine on a
      micromoles per kilogram basis. Substitution of a trisaccharide or bis- and tris
      monosaccharides resulted in a decrease in antinociceptive potency. These results
      provide additional support for the utility of glycosylation to increase central
      nervous system bioavailability of small peptides and compliment our ongoing
      stability and blood-brain barrier penetration studies.

PMID- 15166258
TI  - The N-methyl-D-aspartate receptor inhibitory potencies of aromatic inhaled drugs
      of abuse: evidence for modulation by cation-pi interactions.
AB  - Benzene and several close structural analogs are inhaled drugs of abuse with
      general anesthetic activity. By virtue of their pi electron clouds, they may
      engage in attractive electrostatic interactions with cationic atomic charges on
      protein targets. In this study, we tested the hypothesis that inhaled drugs of
      abuse inhibit human N-methyl-D-aspartate (NMDA) receptors with potencies that
      correlate with their abilities to engage in cation-pi interactions.
      Electrophysiological techniques were used to define the NR1/NR2B NMDA receptor
      inhibitory concentrations of volatile benzene analogs, and computer modeling was
      used to quantify their abilities to engage in cation-pi interactions and their
      molecular volumes. In addition, each compound's octanol/gas partition coefficient
      (a measure of hydrophobicity) was quantified. All 18 compounds inhibited human
      NR1/NR2B NMDA receptors reversibly and in a concentration-dependent manner. NMDA
      receptor inhibitory potency correlated strongly with the ability to engage in
      cation-pi interactions, weakly with hydrophobicity, and was independent of
      molecular volume. This is consistent with the hypothesis that cation-pi
      interactions enhance the binding of inhaled drugs of abuse to the NMDA receptor
      and suggests that the receptor binding site(s) for these drugs possesses
      significant cationic character.

PMID- 15166259
TI  - Mouse models of childhood cancer of the nervous system.
AB  - Targeted cancer treatments rely on understanding signalling cascades, genetic
      changes, and compensatory programmes activated during tumorigenesis.
      Increasingly, pathologists are required to interpret molecular profiles of tumour
      specimens to target new treatments. This is challenging because cancer is a
      heterogeneous disease-tumours change over time in individual patients and genetic
      lesions leading from preneoplasia to malignancy can differ substantially between
      patients. For childhood tumours of the nervous system, the challenge is even
      greater, because tumours arise from progenitor cells in a developmental context
      different from that of the adult, and the cells of origin, neural progenitor
      cells, show considerable temporal and spatial heterogeneity during development.
      Thus, the underlying mechanisms regulating normal development of the nervous
      system also need to be understood. Many important advances have come from model
      mouse genetic systems. This review will describe several mouse models of
      childhood tumours of the nervous system, emphasising how understanding the normal
      developmental processes, combined with mouse models of cancer and the molecular
      pathology of the human diseases, can provide the information needed to treat
      cancer more effectively.

PMID- 15166261
TI  - Identification of three novel RB1 mutations in Brazilian patients with
      retinoblastoma by "exon by exon" PCR mediated SSCP analysis.
AB  - AIMS: To carry out a retrospective study, screening for mutations of the entire
      coding region of RB1 and adjacent intronic regions in patients with
      retinoblastoma. METHODS: Mutation screening in DNA extracts of formalin fixed,
      paraffin wax embedded tissues of 28 patients using combined "exon by exon"
      polymerase chain reaction mediated single strand conformational polymorphism
      analysis, followed by DNA sequencing. RESULTS: Eleven mutations were found in 10
      patients. Ten mutations consisted of single base substitutions; 10 were localised
      in exonic regions (eight nonsense, one missense, and one frameshift) and another
      one in the intron-exon splicing region. Three novel mutations were identified: a
      2 bp insertion in exon 2 (g.5506-5507insAG, R73fsX77), a G to A transition
      affecting the last invariant nucleotide of intron 13 (g.76429G>A), and a T to C
      transition in exon 20 (g.156795T>C, L688P). In addition, eight C to T
      transitions, resulting in stop codons, were found in five different CGA codons
      (g.64348C>T, g.76430C>T, g.78238C>T, g.78250C>T, and g.150037C>T). Although
      specific mutation hotspots have not been identified in the literature, eight of
      the 11 mutations occurred in CGA codons and seven fell within the E1A binding
      domains (codons 393-572 and 646-772), whereas five were of both types-in CGA
      codons within E1A binding domains. CONCLUSIONS: CGA codons and E1A binding
      domains are apparently more frequent mutational targets and should be initially
      screened in patients with retinoblastoma. Paraffin wax embedded samples proved to
      be valuable sources of DNA for retrospective studies, providing useful
      information for genetic counselling.

PMID- 15166260
TI  - Membrane associated proteases and their inhibitors in tumour angiogenesis.
AB  - Cell surface proteolysis is an important mechanism for generating biologically
      active proteins that mediate a range of cellular functions and contribute to
      biological processes such as angiogenesis. Although most studies have focused on
      the plasminogen system and matrix metalloproteinases (MMPs), recently there has
      been an increase in the identification of membrane associated proteases,
      including serine proteases, ADAMs, and membrane-type MMPs (MT-MMPs). Normally,
      protease activity is tightly controlled by tissue inhibitors of MMPs (TIMPs) and
      plasminogen activator inhibitors (PAIs). The balance between active proteases and
      inhibitors is thought to determine the occurrence of proteolysis in vivo. High
      concentrations of proteolytic system components correlate with poor prognosis in
      many cancers. Paradoxically, high (not low) PAI-1 or TIMP concentrations predict
      poor survival in patients with various cancers. Recent observations indicate a
      much more complex role for protease inhibitors in tumour progression and
      angiogenesis than initially expected. As knowledge in the field of protease
      biology has improved, the unforeseen complexities of cell associated enzymes and
      their interaction with physiological inhibitors have emerged, often revealing
      unexpected mechanisms of action.

PMID- 15166263
TI  - Tissue invasiveness and non-acidic pH in human candidiasis correlate with "in
      vivo" expression by Candida albicans of the carbohydrate epitope recognised by
      new monoclonal antibody 1H4.
AB  - BACKGROUND: The morphogenetic conversion between yeast and hyphal growth forms
      appears to be crucial in the pathogenesis of invasive candidiasis, and can be
      regulated by environmental signals such as extracellular pH. AIMS: To
      characterise the epitope recognised by monoclonal antibody 1H4, and to evaluate
      the expression of its corresponding epitope in Candida albicans cells under
      different conditions of pH and temperature, and "in vivo", in tissue samples from
      patients with human candidiasis. METHODS: Monoclonal antibody 1H4 was generated
      against the 58 kDa cell wall mannoprotein of C albicans (mp58), and was further
      characterised by immunoblot analysis, periodate treatment of the antigenic
      preparations, and agglutination experiments of C albicans strains 3153A, SC5314,
      and 412, cultured under different environmental conditions (growth media and pH).
      An immunohistochemical study was performed in 24 human tissue samples from
      patients with mucocutaneous and systemic candidiasis. RESULTS: 1H4 recognises a
      pH sensitive carbohydrate epitope on the surface of C albicans cells, and this
      epitope is not restricted to mp58, but is shared with other cell wall
      mannoproteins. Immunohistochemical findings indicated that expression of the 1H4
      epitope on C albicans cells in tissue sections from human candidiasis correlates
      with tissue invasion and pH of the niche. 1H4 immunoreactivity was also found in
      candida remnants within macrophages. CONCLUSIONS: The fact that 1H4 epitope
      expression selectively identifies invasive forms of C albicans, in addition to
      candida remnants within macrophages, supports its potential value in the
      diagnosis and management of human candidiasis.

PMID- 15166264
TI  - Systemic mastocytosis with associated clonal haematological non-mast cell lineage
      diseases: a histopathological challenge.
AB  - AIMS: Although systemic mastocytosis (SM) with an associated clonal
      haematological non-mast cell lineage disease (SM-AHNMD) is a major subtype of SM,
      little is known about its frequency among myelogenous neoplasms, and mastocytosis
      in particular, or about AHNMD subtype frequencies. METHODS: Approximately 19500
      routine bone marrow biopsies were evaluated. Immunostaining with antibodies
      against tryptase, KIT, and CD25 and molecular analysis for detection of C-KIT
      point mutations were performed in approximately 550/4100 myelogenous malignancies
      including mastocytosis, almost all subtypes of myelodysplastic syndrome (MDS),
      myelodysplastic/myeloproliferative syndrome (MDS/MPD), MPD, and acute myeloid
      leukaemia (AML). RESULTS: SM was rare-it was diagnosed in only 64 bone marrows
      (0.3%) and made up 1.5% of myelogenous tumours. SM-AHNMD was the second most
      frequent subtype (20). SM-AHNMD was never included in the clinical differential
      diagnoses and was confirmed histologically in most cases only after appropriate
      immunostaining. The abnormal mast cell phenotype was confirmed by
      immunohistochemical demonstration of tryptase and CD25 coexpression. The
      following associated haematological neoplasms were found: MDS/MPS, AML, MPS, MDS,
      plasma cell myeloma, and unclassifiable myelogenous malignancy. C-KIT point
      mutations were detected in 16 of 20 cases. CONCLUSIONS: SM-AHNMD can be diagnosed
      histologically in bone marrow trephines only after immunostaining with antibodies
      against tryptase, KIT, and CD25. Eighteen of 20 AHNMDs were of myeloid origin. C
      KIT point mutations were present in 16 of 20 cases. The prognostic relevance of
      detecting SM associated with another haematological neoplasm remains unclear, but
      mast cell resistance to most cytoreductive agents is of major importance for
      treatment planning.

PMID- 15166265
TI  - Do Toxoplasma gondii RH strain tachyzoites evolve during continuous passage?
AB  - AIM: To examine three lineages of Toxoplasma gondii RH strain in terms of
      performance in the dye test, culture, and gene expression. METHODS: Historical
      data (culture growth and performance in the dye test) from three lineages of RH
      strain tachyzoites (B, J, and Q) that had been continuously cultured in HeLa
      cells was assessed. Tachyzoite harvests obtained during continuous cell culture
      were retrieved from liquid nitrogen and cultured in HeLa cells, providing mRNA
      that was extracted and used to study gene expression using random amplified
      polymorphic DNA analysis at different stages of lineage adaptation to continuous
      culture. RESULTS: The B and Q lineages consistently produced tachyzoites that
      were successfully used in the dye test and their gene expression was stable after
      multiple passages. The J lineage had unpredictable growth, tachyzoites unsuitable
      for use in the dye test, and changing gene expression with multiple passage.
      CONCLUSION: This study has explained some anomalies in the performance of
      different stocks of T gondii, and suggests that lineages that are still evolving
      in cell culture should be avoided.

PMID- 15166262
TI  - Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel
      invasion after radical surgery for IB-IIA non-small cell lung cancer.
AB  - AIMS: To evaluate the prognostic impact of tumour angiogenesis assessed by
      vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour
      vessel invasion in patients who had undergone radical resection for stage IB-IIA
      non-small cell lung cancer (NSCLC). METHODS: Fifty one patients (42 men, nine
      women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35
      lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8)
      NSCLC were evaluated retrospectively. No patient underwent postoperative
      chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and
      specific MVD markers: CD31, CD34, and CD105. RESULTS: VEGF expression
      significantly correlated with high CD105 expression (p < 0.0001) and tumour
      vessel invasion (p = 0.04). Univariate analysis showed that those patients with
      VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by
      CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter
      overall survival. Furthermore, multivariate Cox regression analysis showed that
      MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression
      (p = 0.042) were significant predictive factors for overall survival. Finally,
      the presence of both risk factors, tumour vessel invasion and MVD by CD34, was
      highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7
      to 6.5; p = 0.0002). CONCLUSIONS: High MVD by CD34 and tumour vessel invasion are
      more closely related to poor survival than the other neoangiogenetic factors in
      stage IB-IIA NSCLC. This may be because these factors are more closely related to
      the metastatic process.

PMID- 15166266
TI  - Heterogeneity of the fibre sequence in subgenus C adenoviruses.
AB  - AIMS: To determine the nucleotide sequences of adenovirus (Ad) types 1 and 6
      fibre genes; to clarify the molecular basis of the distinct haemagglutination
      properties of subgenus C Ads and their phylogenetic relations. METHODS: Human Ad1
      and Ad6 fibre genes were sequenced from genomic DNA by direct sequencing. Primer
      selection was based on alignment of the fibre gene of human Ad serotypes Ad2 and
      Ad5. Fibre based subgenus C specific polymerase chain reaction (PCR) was
      performed to check for deletions in field isolates of Ad6, as revealed by
      sequence analysis of the Ad6 prototype. A phylogenetic tree was constructed from
      the predicted amino acid (AA) sequences of the fibre gene of important Ads.
      RESULTS: Ad1 and Ad6 comprise 1746 and 1584 nucleotides, encoding 582 and 528 AA,
      respectively. Ad6 showed deletions in motifs 15-17 (51 AA) of the shaft when
      compared with Ad1, Ad2, and Ad5. Subgenus C specific PCR with both prototype and
      field isolates also showed deletions in Ad6. In the shaft and knob, AA homology
      was 58.82-72.91% and 68.89-74.59%, respectively. The tail was 100% conserved.
      Phylogenetically, Ad1 and Ad6, including Ad2 and Ad5, formed a subgenus specific
      cluster, like other serotypes. CONCLUSIONS: The fibre gene (including the knob
      region) of subgenus C Ads is heterogeneous, providing the molecular basis for
      lack of crossreactivity in the haemagglutination inhibition test. This
      heterogeneity could be helpful in fibre based genotyping of subgenus C field
      isolates. Phylogeny might be useful for subgenus specific identification of
      important field strains.

PMID- 15166268
TI  - High prevalence of haemosiderin accumulation in the cytoplasm of gastric glands
      in patients with liver cirrhosis.
AB  - AIMS: To investigate the presence of iron in biopsy and resection specimens from
      the stomach of patients with hepatic cirrhosis of various aetiologies. METHODS:
      Among 753 patients who had been admitted to the hospital with liver cirrhosis
      from 1984 to 2002, and 723 patients who underwent liver biopsy or liver resection
      from 1990 to 2003, 426 patients with concomitant gastric biopsy or gastrectomy
      were selected for study. Formalin fixed, paraffin wax embedded tissues of the
      stomach and the liver (when available) were retrieved from the pathology files of
      Kariya General Hospital, Japan. Haematoxylin and eosin staining and Perls' stain
      were performed for all the available tissues and haemosiderin and its
      localisation were examined. RESULTS: In total, 78 patients-72 of those with
      cirrhosis (26%) and six without cirrhosis (4%)-showed accumulation of
      haemosiderin. Regardless of aetiology, patients with clinical varices showed more
      frequent haemosiderin accumulation (40%) than patients without varices (19%). For
      patients with cirrhosis, there were no significant differences in the positive
      rate between those with (28%) or without (23%) hepatocellular carcinoma.
      CONCLUSION: The significant increase in haemosiderin deposition in the gastric
      glands of patients with cirrhosis suggests that the assessment of iron deposition
      in gastric biopsy specimens may have predictive value in controlling patients
      with cirrhosis.

PMID- 15166267
TI  - Sentinel lymph node investigation in melanoma: detailed analysis of the yield
      from step sectioning and immunohistochemistry.
AB  - AIMS: To evaluate in detail the extent to which step sectioning and
      immunohistochemical examination of sentinel lymph nodes (SLNs) in patients with
      melanoma reveal additional node positive patients, to arrive at a sensitive yet
      workable protocol for histopathological SLN examination. METHODS: The study
      comprised 29 patients with one or more positive SLN after a successful SLN
      procedure for clinical stage I/II melanoma. SLNs were lamellated into pieces of
      approximately 0.5 cm in size. One initial haematoxylin and eosin (H&E) stained
      central cross section was made for each block. When negative, four step ribbons
      were cut at intervals of 250 microm. One section from each ribbon was stained
      with H&E, and one was used for immunohistochemistry (IHC). RESULTS: When taking
      the cumulative total of detected metastases at level 5 as 100%, the percentage of
      SLN positive patients increased from 79%, 83%, 83%, 90% to 93% in the H&E
      sections through levels 1-5, and with IHC these values were 83%, 86%, 90%, 97%,
      and 100%, respectively. One of six patients in whom metastases were detected at
      levels 2-5 only had metastases in the subsequent additional lymph node
      dissection. CONCLUSIONS: Multiple level sectioning of SLNs (five levels at 250
      microm intervals) and the use of IHC detects additional metastases up to the last
      level in melanoma SLNs. Although more levels of sectioning might increase the
      yield even further, this protocol ensures a reasonable workload for the
      pathologist with an acceptable sensitivity when compared with the published
      literature.

PMID- 15166269
TI  - Immunostaining patterns of myoepithelial cells in breast lesions: a comparison of
      CD10 and smooth muscle myosin heavy chain.
AB  - BACKGROUND: Recent studies have reported CD10 expression in myoepithelial cells
      (MEC) of the breast, supporting its use as a marker to help distinguish invasive
      breast carcinoma (IC) from ductal carcinoma in situ (DCIS). AIM: To compare the
      effectiveness of CD10 with smooth muscle myosin heavy chain (SMMHC) in the
      detection of MEC in benign and malignant breast lesions. METHODS: Histological
      material from 25 patients with DCIS and 21 with IC were immunostained for CD10
      and SMMHC. Staining was scored on a scale of 0 to 3+ (0, no staining; 3+,
      intense) and the staining distribution was documented as focal, partial, or
      circumferential. RESULTS: Uniform, 3+ circumferential CD10 and SMMHC staining of
      MEC was seen in normal breast ducts and lobules, and in ducts and acini involved
      in sclerosing adenosis and apocrine metaplasia. In an analysis of total ducts
      involved by DCIS, 3+ circumferential staining was seen in 65 of 366 ducts (17.7%)
      stained for CD10 versus 190 of 396 ducts (48%) stained for SMMHC. MEC were not
      detected immunohistochemically in 116 of 366 ducts (31.7%) with anti-CD10 and 50
      of 396 (12.7%) with anti-SMMHC. In contrast, all ICs were negative for both CD10
      and SMMHC. Focal background staining of stromal myofibroblasts was seen with both
      CD10 and SMMHC, but CD10 showed a higher rate of non-specific staining of
      epithelial cells. CONCLUSION: Although CD10 can aid in the distinction between IC
      and DCIS, SMMHC is a more sensitive and specific marker of MEC and shows less
      heterogeneity of immunostaining patterns.

PMID- 15166271
TI  - Use of multiple displacement amplification to amplify genomic DNA before
      sequencing of the alpha and beta haemoglobin genes.
AB  - AIMS: To evaluate the technique of multiple displacement amplification (MDA) for
      whole genome amplification from small volume blood samples before sequencing in a
      clinical test to identify haemoglobin gene mutations. METHODS: Phage phi29 DNA
      polymerase was used to perform MDA, starting with either 1 micro l of blood or 1
      ng of previously isolated blood DNA from 23 patients. The amplified products were
      then evaluated using a clinical test that involves sequencing the haemoglobin
      genes to detect mutations. The results were compared with the current clinical
      test method that uses genomic DNA isolated using column based technology.
      RESULTS: The MDA technique produced large quantities (theoretically approximately
      2 mg) of DNA. The amplification procedure was extremely easy and took about four
      hours (less than one hour of hands on technician time and three hours for
      amplification). When MDA products were used in the same clinical test protocol as
      genomic DNA isolated using column technology, there was 100% concordance for
      detection of a variety of point mutations in the alpha1, alpha2, and beta globin
      genes. CONCLUSIONS: The MDA technique is useful for overcoming the problem of
      insufficient genomic DNA in clinical specimens requiring haemoglobin gene
      sequencing and could be useful for other clinical applications.

PMID- 15166270
TI  - Inflammatory cells contribute to the generation of an angiogenic phenotype in
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Inflammatory cells contribute to the growth and spread of human
      malignancies by producing molecules that enhance tumour invasiveness. AIMS: To
      characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and
      to analyse its contribution to angiogenesis and its prognostic relevance.
      METHODS: Immunohistochemistry was used to identify inflammatory cells and
      evaluate the expression of proangiogenic and prolymphangiogenic molecules
      (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast
      growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers.
      Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial
      cell marker. RESULTS: There were significantly more mast cells and macrophages in
      pancreatic cancers than in normal pancreas and the number of mast cells directly
      correlated with the presence of lymph node metastases. However, there was no
      relation between numbers of infiltrating inflammatory cells and the presence of
      chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour.
      Double immunostaining revealed that both pancreatic mast cells and macrophages
      express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour
      cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF
      expressing tumour and inflammatory cells significantly correlated with IMD.
      Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells
      and macrophages. CONCLUSIONS: Mononuclear inflammatory cells of the non-specific
      immune response are recruited to pancreatic cancer tissues independent of the
      presence of CP-like changes, may influence the metastatic capacity of the cancer
      cells, and may contribute to the development of tumours with high angiogenic
      activity.

PMID- 15166273
TI  - High resolution microarray comparative genomic hybridisation analysis using
      spotted oligonucleotides.
AB  - BACKGROUND: Currently, comparative genomic hybridisation array (array CGH) is the
      method of choice for studying genome wide DNA copy number changes. To date,
      either amplified representations of bacterial artificial chromosomes (BACs)/phage
      artificial chromosomes (PACs) or cDNAs have been spotted as probes. The
      production of BAC/PAC and cDNA arrays is time consuming and expensive. AIM: To
      evaluate the use of spotted 60 mer oligonucleotides (oligos) for array CGH.
      METHODS: The hybridisation of tumour cell lines with known chromosomal
      aberrations on to either BAC or oligoarrrays that are mapped to the human genome.
      RESULTS: Oligo CGH was able to detect amplifications with high accuracy and
      greater spatial resolution than other currently used array CGH platforms. In
      addition, single copy number changes could be detected with a resolution
      comparable to conventional CGH. CONCLUSIONS: Oligos are easy to handle and
      flexible, because they can be designed for any part of the genome without the
      need for laborious amplification procedures. The full genome array, containing
      around 30000 oligos of all genes in the human genome, will represent a big step
      forward in the analysis of chromosomal copy number changes. Finally, oligoarray
      CGH can easily be used for any organism with a fully sequenced genome.

PMID- 15166272
TI  - CDX-2 immunostaining in primary and secondary ovarian carcinomas.
AB  - AIMS: To assess the value of homeobox protein CDX-2 expression in the distinction
      between primary ovarian carcinomas and carcinomas metastatic to the ovary.
      METHODS: CDX-2 expression was assessed by immunohistochemistry in 120 serous, 68
      endometrioid, 24 clear cell, and 16 mucinous carcinomas of the ovary. In
      addition, CDX-2 immunoreactivity was investigated in 20 metastases from
      adenocarcinomas to the ovary (15 of colorectal, two of gastric, one of
      appendiceal, one of pancreatic, and one of cervical origin) and their
      corresponding primary tumours. RESULTS: Almost all of the primary ovarian
      carcinomas lacked immunoreactivity for CDX-2. In contrast, 14 of the 16
      metastases to the ovary from intestinal primaries showed CDX-2 immunoexpression.
      CONCLUSION: CDX-2 is a useful marker for differentiating primary ovarian
      carcinoma from carcinomas metastatic to the ovary.

PMID- 15166274
TI  - Resistance to scrapie in PrP ARR/ARQ heterozygous sheep is not caused by
      preferential allelic use.
AB  - BACKGROUND: In sheep, susceptibility to scrapie, which is similar to human prion
      diseases such as Kuru and variant Creutzfeldt-Jakob disease (vCJD), is determined
      by prion protein (PrP) gene (Prnp) polymorphisms. Sheep with genotype ARQ/ARQ,
      denoting polymorphisms at codons 136, 154, and 171, are susceptible, whereas
      those with genotypes ARR/ARQ and ARR/ARR are resistant, indicating dominance of
      ARR over the ARQ allele. AIMS: Based on familial CJD E200K, 129V, where
      preferential use of the 200E allele in EK heterozygous individuals confers
      resistance, heterozygous ARR/ARQ sheep were used to test the hypothesis that
      resistance is caused by preferential use of the ARR allele. METHODS: After
      assessment of equivalent PrP expression across genotypes, allele use was analysed
      by sequencing reverse transcription polymerase chain reaction derived DNA clones
      containing the Prnp gene coding sequence. RESULTS: The ARR to ARQ ratio was 1.1
      in 133 clones, representing Prnp mRNA from three ARR/ARQ sheep, indicating equal
      use of both alleles. CONCLUSIONS: Dominance of the resistant associated allele in
      sheep scrapie involves mechanisms other than the absence of PrP derived from the
      disease associated ARQ allele.

PMID- 15166275
TI  - Leukaemia/lymphoma cell microparticles in childhood mature B cell neoplasms.
AB  - AIMS: Because of the observation of an abundance of leukaemia/lymphoma cell
      microparticles in the bone marrow aspiration sample of a patient with Burkitt's
      leukaemia at diagnosis, the occurrence of this phenomenon in leukaemia/lymphoma
      samples with available immune phenotyping data was investigated retrospectively.
      METHODS: Flow cytometric immune phenotyping and spontaneous apoptosis analysis of
      the bone marrow mononuclear cell preparation of the index case were performed.
      Microparticles isolated form the bone marrow sample were also studied for the
      presence of leukaemia/lymphoma cell microparticles. List mode analysis of 225
      cases of acute leukaemia or lymphoma with previously performed immune phenotyping
      was also carried out. RESULTS: The presence of leukaemia/lymphoma cell
      microparticles could be detected by flow cytometry and they were found to be
      different from apoptotic bodies. Leukaemia/lymphoma cell microparticles were
      released in all cases of mature B cell neoplasms studied, although this
      phenomenon was rare in precursor B cell disorders and acute myeloid leukaemia.
      CONCLUSIONS: The generation of leukaemia/lymphoma cell microparticles in mature B
      cell neoplasms appears to be a common phenomenon. The pathogenesis and clinical
      implications must be investigated.

PMID- 15166276
TI  - Effect of buffered formalin on amplification of DNA from paraffin wax embedded
      small biopsies using real-time PCR.
AB  - BACKGROUND: The isolation of good quality DNA from routinely fixed and processed
      biopsy samples is crucial for the success of subsequent molecular analysis. AIMS:
      To compare the amount of beta actin DNA extracted from upper gastrointestinal
      tract biopsies fixed in buffered and unbuffered formalin. METHODS: Amounts of
      beta actin DNA extracted from forceps biopsies of the upper gastrointestinal
      tract fixed in unbuffered (n = 22) and buffered formalin (n = 16) were estimated
      by quantitative real-time polymerase chain reaction. RESULTS: The yield of beta
      actin DNA was significantly higher in biopsies fixed in buffered formalin than in
      those fixed in unbuffered formalin (median 2.8 x 10(4) and 5.3 x 10(2) DNA
      molecules, respectively; p < 0.005). Furthermore, fixation in buffered formalin
      led to a more reproducible DNA extraction, as indicated by the coefficient of
      variation (1.0 and 2.2, respectively). CONCLUSIONS: This study indicates that
      tissue samples should be fixed in buffered formalin to facilitate the use of
      molecular pathology analysis in routine biopsy material.

PMID- 15166277
TI  - Chlamydia trachomatis serovar E isolates from patients with different clinical
      manifestations have similar courses of infection in a murine model: host factors
      as major determinants of C trachomatis mediated pathogenesis.
AB  - BACKGROUND: Some investigators have proposed an association between certain
      Chlamydia trachomatis serovars and the clinical course of infection in humans. A
      recent study of over 1100 patients with culture confirmed and serotyped C
      trachomatis urogenital infection detected no such association. AIMS: To
      corroborate these results using a murine model of female genital tract infection.
      METHODS: Various parameters of infection were assessed in mice intravaginally
      infected with human genital isolates of C trachomatis serovar E from four cases
      with either a clear symptomatic or asymptomatic clinical course in both the
      patient and their partner. RESULTS: No differences were seen among the strains in
      the incidence or duration of infection, polymorphonuclear granulocyte responses,
      or upper genital tract progression. CONCLUSIONS: An investigation to determine
      the correlation between the clinical manifestations of different isolates of C
      trachomatis serovar E in humans and certain parameters of microbial pathogenesis
      in a mouse model failed to reveal an association between the measured parameters
      and the tendency of serovar E to produce symptomatic versus asymptomatic
      infections in humans. These findings suggest that differences in the clinical
      course of infection in humans seen with these strains may be more related to host
      factors than to genetic variation among strains.

PMID- 15166278
TI  - Myocardial air collections as a result of infection with a gas producing strain
      of Escherichia coli.
AB  - Certain strains of Escherichia coli have been shown to cause gas accumulation in-
      for example, emphysematous pyelonephritis. This paper describes a patient with
      intramyocardial air collections resulting from an intramyocardial infection with
      gas forming E coli.

PMID- 15166279
TI  - Diagnosis of aspergillus peritonitis in a renal dialysis patient by PCR and
      galactomannan detection.
AB  - This report describes the use of the polymerase chain reaction (PCR) and
      galactomannan detection to detect aspergillus in the continuous ambulatory
      peritoneal dialysis (CAPD) fluid and blood of a patient with multiple myeloma on
      CAPD and immunosuppressive treatment. Diagnosis of aspergillosis was initially
      made by conventional culture of CAPD fluid, but the PCR and galactomannan assays
      also detected aspergillus DNA and antigen in the blood, respectively. This
      suggests that the PCR and galactomannan assays, previously suggested as useful in
      the management of invasive fungal infections in neutropenic haematological
      patients, may be suitable for application to a broad range of clinical situations
      and sample types.

PMID- 15166280
TI  - Treatment difficulties of a listerial rhombencephalitis in an adult patient
      allergic to penicillins.
AB  - Rhombencephalitis is not a rare presentation of listerial central nervous system
      infections in healthy adults. This report describes a case with several
      management difficulties linked to antibiotic related adverse events, pointing to
      alternative solutions to aminopenicillins. In addition, the role of dexamethasone
      in the management of inflammation and neurological symptoms is discussed.

PMID- 15166283
TI  - Authorship trends in the Indian Journal of Pathology and Microbiology: going the
      global way?

PMID- 15166282
TI  - Type A intracytoplasmic inclusions in human cowpox infection.

PMID- 15166281
TI  - Atypical haemolytic uraemic syndrome as a complication of induction chemotherapy
      for acute lymphoblastic leukaemia.
AB  - This report describes a case of fatal haemolytic uraemic syndrome (HUS)
      developing in a child with acute lymphoblastic leukaemia (ALL) during induction
      chemotherapy. The aetiology in this case is uncertain but it may have resulted
      from treatment with L-asparaginase or vincristine. The possibility of HUS during
      induction chemotherapy for ALL should be considered early on in the treatment
      regimen, if clinical signs and symptoms suggest this diagnosis, so that
      appropriate treatment can be instituted.

PMID- 15166284
TI  - Incidental freezing artefacts in sentinel lymph node biopsies masquerading as
      lymphangiography artefacts.

PMID- 15166285
TI  - Omental actinomycosis presenting with right lower quadrant abdominal pain.

PMID- 15166286
TI  - Can routine laboratory data guide empirical prescribing?

PMID- 15166287
TI  - Ferritin reactions: direct identification of the site for the diferric peroxide
      reaction intermediate.
AB  - Ferritins managing iron-oxygen biochemistry in animals, plants, and
      microorganisms belong to the diiron carboxylate protein family and concentrate
      iron as ferric oxide approximately 10(14) times above the ferric K(s). Ferritin
      iron (up to 4,500 atoms), used for iron cofactors and heme, or to trap DNA
      damaging oxidants in microorganisms, is concentrated in the protein nanocage
      cavity (5-8 nm) formed during assembly of polypeptide subunits, 24 in
      maxiferritins and 12 in miniferritins/DNA protection during starvation proteins.
      Direct identification of ferritin ferroxidase (F(ox)) sites, complicated by
      multiple types of iron-ferritin interactions, is now achieved with chimeric
      proteins where putative F(ox) site residues were introduced singly and
      cumulatively into an inactive host, an L maxiferritin. A dimagnesium ferritin
      cocrystal model guided site design and the diferric peroxo F(ox) intermediates (A
      at 650 nm) monitored activity. Diferric peroxo formation in chimeric and WT
      proteins had similar K(app) values and Hill coefficients. Catalytic activity
      required cooperative ferrous substrate binding to two sites A (E, EXXH) and B (E,
      QXXD). The weaker B sites in ferritin contrast with stronger B sites (E, EXXH) in
      diiron carboxylate oxygenases, explaining diferric oxo/hydroxo product release in
      ferritin vs. diiron cofactor retention in oxygenases. Codons for Q/H and D/E
      differ by single nucleotides, suggesting simple DNA mutations relate site B
      diiron substrate sites and diiron cofactor sites in proteins. The smaller k(cat)
      values in chimeras indicate the absence of second-shell residues important for
      ferritin substrate-product channeling that, when identified, will outline the
      entire iron path from ferritin pores through the F(ox) site to the mineral
      cavity.

PMID- 15166288
TI  - Plasmodium falciparum cysteine protease falcipain-1 is not essential in
      erythrocytic stage malaria parasites.
AB  - Among potential new targets for antimalarial chemotherapy are Plasmodium
      falciparum cysteine proteases, known as falcipains. Falcipain-2 and falcipain-3
      are food vacuole hemoglobinases that may have additional functions. The function
      of falcipain-1 remains uncertain. To better characterize the role of falcipain-1
      in erythrocytic parasites, we disrupted the falcipain-1 gene and characterized
      recombinant parasites. Disruption of the falcipain-1 gene was confirmed with
      Southern blots, and loss of expression of falcipain-1 was confirmed with
      immunoblots and by loss of labeling with a specific protease inhibitor. Compared
      with wild-type parasites, falcipain-1 knockout parasites developed normally, with
      the same morphology, multiplication rate, and invasion efficiency, and without
      significant differences in sensitivity to cysteine protease inhibitors. In wild
      type and knockout parasites, cysteine protease inhibitors blocked hemoglobin
      hydrolysis in trophozoites, with a subsequent block in rupture of erythrocytes by
      mature schizonts, but they did not inhibit erythrocyte invasion by merozoites.
      Our results indicate that although falcipain-1 is expressed by erythrocytic
      parasites, it is not essential for normal development during this stage or for
      erythrocyte invasion.

PMID- 15166289
TI  - Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause
      craniofrontonasal syndrome.
AB  - Craniofrontonasal syndrome (CFNS) is an X-linked developmental disorder that
      shows paradoxically greater severity in heterozygous females than in hemizygous
      males. Females have frontonasal dysplasia and coronal craniosynostosis (fusion of
      the coronal sutures); in males, hypertelorism is the only typical manifestation.
      Here, we show that the classical female CFNS phenotype is caused by heterozygous
      loss-of-function mutations in EFNB1, which encodes a member of the ephrin family
      of transmembrane ligands for Eph receptor tyrosine kinases. In mice, the
      orthologous Efnb1 gene is expressed in the frontonasal neural crest and
      demarcates the position of the future coronal suture. Although EFNB1 is X
      inactivated, we did not observe markedly skewed X-inactivation in either blood or
      cranial periosteum from females with CFNS, indicating that lack of ephrin-B1 does
      not compromise cell viability in these tissues. We propose that in heterozygous
      females, patchwork loss of ephrin-B1 disturbs tissue boundary formation at the
      developing coronal suture, whereas in males deficient in ephrin-B1, an
      alternative mechanism maintains the normal boundary. This is the only known
      mutation in the ephrin/Eph receptor signaling system in humans and provides clues
      to the biogenesis of craniosynostosis.

PMID- 15166292
TI  - Intramyocellular lipids and insulin sensitivity: does size really matter?

PMID- 15166290
TI  - In planta functions of the Arabidopsis cytokinin receptor family.
AB  - Since their discovery as cell-division factors in plant tissue culture about five
      decades ago, cytokinins have been hypothesized to play a central role in the
      regulation of cell division and differentiation in plants. To test this
      hypothesis in planta, we isolated Arabidopsis plants lacking one, two, or three
      of the genes encoding a subfamily of histidine kinases (CRE1, AHK2, and AHK3)
      that function as cytokinin receptors. Seeds were obtained for homozygous plants
      containing mutations in all seven genotypes, namely single, double, and triple
      mutants, and the responses of germinated seedlings in various cytokinin assays
      were compared. Both redundant and specific functions for the three different
      cytokinin receptors were observed. Plants carrying mutations in all three genes
      did not show cytokinin responses, including inhibition of root elongation,
      inhibition of root formation, cell proliferation in and greening of calli, and
      induction of cytokinin primary-response genes. The triple mutants were small and
      infertile, with a reduction in meristem size and activity, yet they possessed
      basic organs: roots, stems, and leaves. These results confirm that cytokinins are
      a pivotal class of plant growth regulators but provide no evidence that
      cytokinins are required for the processes of gametogenesis and embryogenesis.

PMID- 15166293
TI  - Melanin-concentrating hormone receptor mutations and human obesity: functional
      analysis.
AB  - Melanin-concentrating hormone (MCH), a neuropeptide highly expressed in the
      lateral hypothalamus, has an important role in the regulation of energy balance
      and body weight in rodents. We examined whether mutations in the two known MCH
      receptors might be associated with obesity-related phenotypes in humans. Among
      106 subjects with severe early onset obesity and a history of hyperphagia, we
      found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found
      in 192 normal weight controls. R248Q cosegregated with obesity across two
      generations; family data were unavailable for Y181H. When expressed in HEK293
      cells, R248Q showed no evidence of constitutive activation or ligand
      hypersensitivity for extracellular signal-regulated kinase phosphorylation. In
      addition, R248Q showed no enhanced suppression of cAMP generation. Two common
      single-nucleotide polymorphisms were found to be in linkage disequilibrium: g.
      114A>G and c.39C>T. No association between either of these single-nucleotide
      polymorphisms and obesity-related phenotypes was found among a population cohort
      of 541 whites. Only two rare noncoding variants were found in MCHR2. In
      conclusion, mutations in the MCH receptors are not commonly found in humans with
      severe early onset obesity. Clarification of the relationship of these variants
      to obesity must await study in other populations and/or in genetically modified
      mice.

PMID- 15166294
TI  - Adipose tissue transcriptome by serial analysis of gene expression.
AB  - OBJECTIVE: To describe the genomic expression profile or transcriptome of adipose
      tissue using the serial analysis of gene expression method. RESEARCH METHODS AND
      PROCEDURES: The serial analysis of gene expression strategy is based on isolation
      of short sequences (tags), which usually correspond to unique transcripts, and on
      their concatenation into long DNA molecules, which are then cloned and sequenced.
      Experiments were performed with mRNA from retroperitoneal adipose tissue of male
      C57BL6 mice. RESULTS: We isolated 45,996 tags corresponding to more than 17,000
      different genes. Eighty-eight genes were expressed at more than 0.1% of the total
      population and represented 26% of the mRNA population identified. The most
      expressed genes were: carbonic anhydrase 3 (1.97%), cytochrome c oxidase (COX) 1
      (1.47%), COX2 (1.25%), diazepam binding inhibitor (1.04%), a novel transcript
      (0.87%), COX3 (0.55%), fatty acid-binding protein 4 (0.55%), and NADH
      dehydrogenase 4 (0.52%). Other genes known to be expressed in adipose tissue,
      such as uncoupling protein 2, angiotensinogen, adipsin, and insulin-like growth
      factor 1, were found at a lower level. Several tags corresponding to novel
      transcripts were also found. DISCUSSION: To our knowledge, the present results
      provide for the first time a quantitative description of the transcriptome in
      adipose tissue.

PMID- 15166295
TI  - Appearance vs. health reasons for seeking treatment among obese patients with
      binge eating disorder.
AB  - OBJECTIVE: This study examined reasons for seeking treatment reported by obese
      patients diagnosed with binge eating disorder (BED). RESEARCH METHODS AND
      PROCEDURES: Participants were 248 adults (58 men and 190 women) who met DSM
      criteria for BED. Participants were recruited through advertisements for
      treatment studies looking for persons who wanted to "stop binge eating and lose
      weight." Patients' reasons for seeking treatment were examined with respect to
      demography (gender and age), obesity (BMI and age of onset), features of eating
      disorders, and associated psychological functioning (depression and self-esteem).
      RESULTS: Of the 248 participants, 64% reported health concerns and 36% reported
      appearance concerns as their primary reason for seeking treatment. Reasons for
      seeking treatment did not differ significantly by gender. Patients seeking
      treatment because of appearance-related reasons had lower BMIs than those
      reporting health-related reasons (34.8 vs. 38.5, respectively), but they reported
      greater body dissatisfaction, more features of eating disorders, and lower self
      esteem. DISCUSSION: Reasons that prompt treatment seeking among obese individuals
      with BED reflect meaningful patient characteristics and, therefore, warrant
      assessment and consideration during treatment planning. Further research is
      needed to determine whether reasons for treatment seeking among different obese
      patient groups affect treatment outcomes.

PMID- 15166296
TI  - Effects of weight loss and physical activity on muscle lipid content and droplet
      size.
AB  - OBJECTIVES: To address the potential effects of weight loss and physical activity
      (WL + Ex) on intramyocellular lipid (IMCL) and lipid droplet size in overweight
      and obese previously sedentary individuals. RESEARCH METHODS AND PROCEDURES: IMCL
      and lipid droplet size was determined in vastus lateralis, obtained by
      percutaneous biopsy, from 21 obese volunteers (9 men/12 women), using Oil Red O
      staining, along with succinate dehydrogenase histochemistry and mitochondrial
      immunohistochemistry as measures of skeletal muscle oxidative capacity. Insulin
      sensitivity (IS) was determined by glucose clamp. RESULTS: A 4-month WL + Ex
      intervention resulted in approximately 10% WL and approximately 15% increase in
      maximal oxygen uptake, leading to a 46% increase in IS (all p < 0.01). IMCL did
      not significantly change (p = 0.36). However, the size of lipid droplets
      decreased after WL + Ex (p < 0.01), and this decrease in lipid droplet size
      correlated with increased IS (p < 0.01) and the amount of physical activity (p <
      0.05). Succinate dehydrogenase activity and mitochondrial labeling increased
      significantly (p < 0.01), without a significant shift in fiber type distribution.
      DISCUSSION: In summary, IMCL does not decrease in response to WL + Ex in obese,
      previously sedentary individuals, yet the lipid within muscle is dispersed into
      smaller droplets. This change in the size of lipid droplets, likely coupled with
      a concomitant increase in oxidative enzyme capacity, is correlated to improved
      IS.

PMID- 15166297
TI  - A human adenovirus enhances preadipocyte differentiation.
AB  - OBJECTIVE: Adenovirus 36 (Ad-36) has been shown to increase adiposity in
      experimentally infected chickens, mice, and marmosets (nonhuman primates).
      Neutralizing antibodies to Ad-36 are associated with obesity in humans. The
      metabolic and molecular mechanisms responsible for Ad-36-induced adipogenesis are
      unknown. As a potential adipogenic mechanism, this study examined if Ad-36
      enhanced differentiation of preadipocytes. RESEARCH METHODS AND PROCEDURES: To
      determine the suitability of 3T3-L1 cells (murine preadipocyte cell line) as a
      model, the first experiment determined if Ad-36 attaches and initiates
      replication in the cells. Next, effects of Ad-36 on the number of differentiated
      adipocytes, glycerol 3-phosphate dehydrogenase (GPDH) levels, and cellular lipid
      accumulation were determined. The last experiment determined the effect of Ad-36
      on human primary preadipocyte differentiation. Ad-2, a known nonadipogenic human
      adenovirus, was used as a negative control in these experiments. RESULTS:
      Immunofluorescence studies showed adenoviral attachment to 3T3-L1 cells, and
      reverse transcriptase-polymerase chain reaction showed expression of the Ad-36
      E1A gene in the infected cells. Ad-36, but not Ad-2, increased the number of
      differentiated adipocytes, GPDH enzyme levels, and the total cellular lipid
      content. Also, Ad-36, but not Ad-2, increased GPDH levels in human preadipocytes.
      DISCUSSION: Taken together, these experiments showed that Ad-36 enhanced
      differentiation of preadipocytes, which may be a contributory mechanism to its
      adipogenic effect in vivo. The lack of effect of Ad-2 on differentiation
      demonstrated that the observed findings were not a common characteristic of all
      adenoviruses. Future understanding of the molecular interactions of cellular and
      viral genes responsible for enhanced differentiation may reveal novel signaling
      pathways and controls of preadipocyte differentiation.

PMID- 15166298
TI  - Sugar-added beverages and adolescent weight change.
AB  - OBJECTIVE: The increase in consumption of sugar-added beverages over recent
      decades may be partly responsible for the obesity epidemic among U.S.
      adolescents. Our aim was to evaluate the relationship between BMI changes and
      intakes of sugar-added beverages, milk, fruit juices, and diet soda. RESEARCH
      METHODS AND PROCEDURES: Our prospective cohort study included >10,000 boys and
      girls participating in the U.S. Growing Up Today Study. The participants were 9
      to 14 years old in 1996 and completed questionnaires in 1996, 1997, and 1998. We
      analyzed change in BMI (kilograms per meter squared) over two 1-year periods
      among children who completed annual food frequency questionnaires assessing
      typical past year intakes. We studied beverage intakes during the year
      corresponding to each BMI change, and in separate models, we studied 1-year
      changes in beverage intakes, adjusting for prior year intakes. Models included
      all beverages simultaneously; further models adjusted for total energy intake.
      RESULTS: Consumption of sugar-added beverages was associated with small BMI gains
      during the corresponding year (boys: +0.03 kg/m2 per daily serving, p = 0.04;
      girls: +0.02 kg/m2, p = 0.096). In models not assuming a linear dose-response
      trend, girls who drank 1 serving/d of sugar-added beverages gained more weight
      (+0.068, p = 0.02) than girls drinking none, as did girls drinking 2 servings/d
      (+0.09, p = 0.06) or 3+ servings/d (+0.08, p = 0.06). Analyses of year-to-year
      change in beverage intakes provided generally similar findings; boys who
      increased consumption of sugar-added beverages from the prior year experienced
      weight gain (+0.04 kg/m2 per additional daily serving, p = 0.01). Children who
      increased intakes by 2 or more servings/d from the prior year gained weight
      (boys: +0.14, p = 0.01; girls +0.10, p = 0.046). Further adjusting our models for
      total energy intake substantially reduced the estimated effects, which were no
      longer significant. DISCUSSION: Consumption of sugar-added beverages may
      contribute to weight gain among adolescents, probably due to their contribution
      to total energy intake, because adjustment for calories greatly attenuated the
      estimated associations.

PMID- 15166299
TI  - Exercise-induced reduction in obesity and insulin resistance in women: a
      randomized controlled trial.
AB  - OBJECTIVES: To determine the effects of equivalent diet- or exercise-induced
      weight loss and exercise without weight loss on subcutaneous fat, visceral fat,
      and insulin sensitivity in obese women. RESEARCH METHODS AND PROCEDURES: Fifty
      four premenopausal women with abdominal obesity [waist circumference 110.1 +/-
      5.8 cm (mean +/- SD)] (BMI 31.3 +/- 2.0 kg/m2) were randomly assigned to one of
      four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise
      without weight loss (n = 12), and a weight-stable control group (n = 10). All
      groups underwent a 14-week intervention. RESULTS: Body weight decreased by
      approximately 6.5% within both weight loss groups and was unchanged in the
      exercise without weight loss and control groups. In comparison with controls,
      cardiorespiratory fitness improved within the exercise groups only (p < 0.01).
      Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise
      weight loss group was greater (p < 0.001) than within all other groups. The
      reduction in total and abdominal fat within the diet weight loss and exercise
      without weight loss groups was greater than within controls (p < 0.001) but not
      different from each other (p > 0.05). Visceral fat decreased within all treatment
      groups (p < 0.008), and these changes were not different from each other. In
      comparison with the control group, insulin sensitivity improved within the
      exercise weight loss group alone (p < 0.001). DISCUSSION: Daily exercise without
      caloric restriction was associated with substantial reductions in total fat,
      abdominal fat, visceral fat, and insulin resistance in women. Exercise without
      weight loss was also associated with a substantial reduction in total and
      abdominal obesity.

PMID- 15166300
TI  - Toward an understanding of health services use in women with binge eating
      disorder.
AB  - OBJECTIVE: This study examined health services use in community samples of 102
      white and 60 black women with binge eating disorder (BED), 164 white and 85 black
      healthy comparison women, and 86 white and 21 black women with a noneating Axis I
      psychiatric disorder. RESEARCH METHODS AND PROCEDURES: Participants were matched
      on age, ethnicity, and education and were asked about their use of emergency room
      visits, outpatient physician visits for medical care, outpatient psychotherapy
      visits, and days spent in the hospital over the previous 12 months. Total health
      services use was computed. RESULTS: There were no between-group differences in
      outpatient physician visits or inpatient hospital days. Relative to healthy
      comparison women, women with BED and women with other Axis I disorders had
      increased total health services use, psychotherapy visits, and emergency
      department visits. Relative to women with noneating Axis I disorders, women with
      BED had less use of psychotherapy visits. Although obese white women were more
      likely to report emergency department visits than obese black women were,
      nonobese white women were less likely to report emergency department visits than
      nonobese black women were. DISCUSSION: That health services use by women with BED
      compared more with that of women with other Axis I disorders than with that of
      healthy women suggested that BED has clinical significance and is not benign in
      terms of its impact on the health care system. It appeared, however, that despite
      the availability of effective treatments, few women with BED received
      psychotherapy.

PMID- 15166301
TI  - Association between body fat response to exercise training and multilocus ADR
      genotypes.
AB  - OBJECTIVE: To examine the contribution of adrenergic receptor (ADR) gene
      polymorphisms and their gene-gene interactions to the variability of exercise
      training-induced body fat response. RESEARCH METHODS AND PROCEDURES: This was an
      intervention study that used a volunteer sample of 70 healthy, sedentary men (n =
      29) and postmenopausal women (n = 41) 50 to 75 years of age, with a BMI < or = 37
      kg/m2, from the Washington, DC, metropolitan area. Participants completed 6 weeks
      of dietary stabilization (American Heart Association diet) before 24 weeks of
      supervised aerobic exercise training. Diet was maintained throughout the
      intervention. Change in percent total body fat, percent trunk fat, and fat mass
      by DXA in ADR genotype groups (Glu12/Glu9 alpha2b-ADR, Trp64Arg beta3-ADR, and
      Gln27Glu beta2-ADR) at baseline and after 24 weeks of aerobic exercise training
      was measured. RESULTS: In multivariate analysis (covariates: age, gender, and
      baseline value of phenotype), best fit models for percent total body and trunk
      fat response to exercise training retained main effects of all three ADR gene
      loci and the effects of each gene-gene interaction (p = 0.009 and 0.003,
      respectively). Similarly, there was a trend for the fat mass response model (p =
      0.03). The combined genetic factors explained 17.5% of the overall model
      variability for percent total body fat, 22% for percent trunk fat, and 10% for
      fat mass. DISCUSSION: The body fat response to exercise training in older adults
      is associated with the combined effects of the Glu12/Glu9 alpha2b-, Trp64Arg
      beta3-, and Gln27Glu beta2-ADR gene variants and their gene-gene interactions.

PMID- 15166302
TI  - Is dietary fat intake related to liking or household availability of high- and
      low-fat foods?
AB  - OBJECTIVE: Despite the increasing availability of low- and reduced-fat foods,
      Americans continue to consume more fat than recommended, which may be a
      contributing factor to the obesity epidemic. This investigation examined
      relationships between liking and household availability of high- and low-fat
      foods and their association with dietary fat intake. RESEARCH METHODS AND
      PROCEDURES: A food frequency questionnaire assessed percent calories from fat
      consumed over the past year in 85 men and 80 women. Participants reported their
      degree of liking 22 "high-fat foods" (>45% calories from fat) and 22 "low-fat
      foods" (<18% calories from fat), and the number and percentage (number of high-
      or low-fat foods/total number of foods x 100) of these high- and low-fat foods in
      their homes. RESULTS: Hierarchical regression analyses examined the ability of
      liking and household availability of low- and high-fat foods to predict percent
      dietary fat intake. After controlling for age, sex, and BMI, liking ratings for
      high- and low-fat foods and the interaction of liking for low-fat foods by the
      percentage of low-fat foods in the household were significant predictors of
      percent dietary fat consumed. Greater liking of high-fat foods and lower liking
      of low-fat foods, both alone and combined with a lower percentage of low-fat
      foods in the home, were predictive of higher dietary fat intake. DISCUSSION:
      Interventions designed to reduce dietary fat intake should target both decreasing
      liking for high-fat foods and increasing liking for low-fat foods, along with
      increasing the proportion of low-fat foods in the household.

PMID- 15166303
TI  - Prevalence of the metabolic syndrome across cardiorespiratory fitness levels in
      women.
AB  - OBJECTIVE: To determine the prevalence of the metabolic syndrome across age
      strata and cardiorespiratory fitness (CRF) levels in women. RESEARCH METHODS AND
      PROCEDURES: 7104 women underwent a physical examination, including a maximal
      treadmill exercise test. Participants were divided into CRF quintiles according
      to age. The metabolic syndrome was identified using Adult Treatment Panel-III
      Guidelines. Tests for trend were performed on demographic variables across CRF
      quintiles, as well as prevalence of the metabolic syndrome across CRF quintiles,
      age strata, and maximal workload achieved [maximal metabolic equivalent (MET)
      level]. RESULTS: The overall prevalence of the metabolic syndrome was 6.5%. Age-
      and smoking-adjusted prevalence was lower across quintiles of CRF (19.0%, 6.7%,
      6.0%, 3.6%, and 2.3% for quintiles I to V, respectively, p for trend = 0.001).
      Smoking-adjusted prevalence of the metabolic syndrome was higher across age
      strata (2.4%, 2.7%, 6.4%, 8.7%, 15.3%, and 16.1% for ages 20 to 29, 30 to 39, 40
      to 49, 50 to 59, 60 to 69, and 70 to 80, respectively, p for trend = 0.001).
      Prevalence of the metabolic syndrome in the different age groups for women who
      achieved a maximal MET level of 11 or higher was one-third to one-fourth that of
      women who achieved lower maximal MET levels. DISCUSSION: Prevalence of the
      metabolic syndrome was markedly lower across progressively higher levels of CRF
      in women of different age strata. Because regular physical activity improves
      components of the metabolic syndrome, modest increases in CRF among low fit women
      may ameliorate the metabolic syndrome in some instances.

PMID- 15166304
TI  - Insulin sensitivity, body fat distribution, and family diabetes history: the IRAS
      Family Study.
AB  - OBJECTIVE: Markers of insulin resistance are often apparent in nondiabetic
      relatives of subjects with type 2 diabetes. Whether diabetes family history (FH)
      also predicts visceral fat accumulation and, if so, whether the increased insulin
      resistance in relatives of diabetic subjects occurs independently of visceral fat
      accumulation are not known. RESEARCH METHODS AND PROCEDURES: To examine this
      issue, we studied the relationship of diabetes FH with insulin sensitivity and
      fat measures, measured by minimal model analysis and computed tomography,
      respectively, in families participating in the Insulin Resistance Atherosclerosis
      (IRAS) Family Study. FH scores were based on the diabetes status of the
      participants' parents and older siblings. RESULTS: FH scores were significantly
      correlated with reduced insulin sensitivity (p < 0.05) and increased subcutaneous
      (p < 0.05) and visceral (p < 0.05, San Antonio only) fat in families from San
      Antonio and Los Angeles but not in the leaner Hispanic families from San Luis
      Valley. There was no evidence for a stronger association of FH score with
      visceral fat accumulation than with subcutaneous fat or insulin resistance.
      DISCUSSION: The absence of an association between FH score and insulin
      resistance/fat accumulation in San Luis Valley is consistent with the idea that
      the expression of transmitted diabetes genes may be suppressed in leaner, more
      physically active populations.

PMID- 15166305
TI  - Resting metabolic rate in severely obese diabetic and nondiabetic subjects.
AB  - OBJECTIVES: To compare the resting metabolic rate (RMR) between diabetic and
      nondiabetic obese subjects and to develop a predictive equation of RMR for these
      subjects. RESEARCH METHODS AND PROCEDURES: Obese adults (1088; mean age = 44.9 +/
      12.7 years) with BMI > or = 35 kg/m2 (mean BMI = 46.4 +/- 8.4 kg/m2) were
      recruited. One hundred forty-two subjects (61 men, 81 women) were diagnosed with
      type 2 diabetes (DM), giving the prevalence of DM in this clinic population as
      13.7%. RMR was measured by indirect calorimetry, and several multivariate linear
      regression models were performed using age, gender, weight, height, BMI, fat
      mass, fat mass percentage, and fat-free mass as independent variables. RESULTS:
      The severely obese patients with DM had consistently higher RMR after adjustment
      for all other variables. The best predictive equation for the severely obese was
      RMR = 71.767 - 2.337 x age + 257.293 x gender (women = 0 and men = 1) + 9.996 x
      weight (in kilograms) + 4.132 x height (in centimeters) + 145.959 x DM
      (nondiabetic = 0 and diabetic = 1). The age, weight, and height-adjusted least
      square means of RMR between diabetic and nondiabetic groups were significantly
      different in both genders. DISCUSSION: Severely obese patients with type 2
      diabetes had higher RMR than those without diabetes. The RMR of severely obese
      subjects was best predicted by an equation using age, gender, weight, height, and
      DM as variables.

PMID- 15166306
TI  - Height and adiposity among children.
AB  - OBJECTIVE: Although BMI (kilograms per meter squared) is widely used as a
      surrogate measure of adiposity, it is moderately associated (r approximately 0.3)
      with height among children. We examined whether the resulting preferential
      classification of taller children as overweight, based on a BMI > or = 95th
      percentile, is appropriate. RESEARCH METHODS AND PROCEDURES: We assessed the
      cross-sectional relation of height among 5- to 18-year-old subjects (n = 1180) to
      levels of BMI, the sum of 10 skinfold thicknesses, and percentage body fat as
      determined by DXA. RESULTS: The prevalence of a BMI level > or = 95th percentile
      was substantially higher among 5- to 11-year-old subjects who were relatively
      tall for their age than among shorter children. Among 5- to 8-year-old boys, for
      example, each SD increase in height-for-age was associated with a 4.6-fold
      increase in the prevalence of overweight (p < 0.001). Height not only was
      associated with BMI but also showed similar correlations with the skinfold sum
      and with percentage body fat; furthermore, the magnitudes of these associations
      decreased with age. We also found that the association between percentage body
      fat and BMI (r = 0.85 to 0.90) was close to the maximum correlation that can be
      achieved by any weight-height index. DISCUSSION: The use of BMI, which
      preferentially classifies taller young children as overweight, is appropriate
      because height and adiposity are correlated before the age of 12 years.

PMID- 15166307
TI  - Disability, arthritis, and body weight among adults 45 years and older.
AB  - OBJECTIVE: To examine the association between body weight and disability among
      persons with and without self-reported arthritis. RESEARCH METHODS AND
      PROCEDURES: Data were analyzed for noninstitutionalized adults, 45 years or
      older, in states that participated in the Behavioral Risk Factor Surveillance
      System. Self-reported BMI (kilograms per meter squared) was used to categorize
      participants into six BMI-defined groups: underweight (<18.5), normal weight
      (18.5 to < 25), overweight (25 to < 30), obese, class 1 (30 to < 35), obese,
      class 2 (35 to < 40), and obese, class 3 (> or = 40). RESULTS: Class 3 obesity
      (BMI > or = 40) was significantly associated with disability among participants
      both with and without self-reported arthritis. The adjusted odds ratio (AOR) for
      disability in participants with class 3 obesity was 2.75 [95% confidence interval
      (CI) = 2.22 to 3.40] among those with self-reported arthritis and 1.77 (95% CI =
      1.20 to 2.62) among those without self-reported arthritis compared with those of
      normal weight (BMI 18.5 to < 25). Persons with self-reported arthritis who were
      obese, class 2 (BMI 35 to < 40) and obese, class 1 (BMI 30 to <35) and women with
      self-reported arthritis who were overweight (BMI 25 to < 30) also had higher odds
      of disability compared with those of normal weight [AOR = 1.72 (95% CI = 1.47 to
      2.00), AOR = 1.30 (95% CI = 1.17 to 1.44), and AOR = 1.18 (95% CI = 1.06 to
      1.32), respectively]. DISCUSSION: Our findings reveal that obesity is associated
      with disability. Preventing and controlling obesity may improve the quality of
      life for persons with and without self-reported arthritis.

PMID- 15166308
TI  - Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases
      SGK1, SGK3, and PKB.
AB  - OBJECTIVE: Serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibits the
      ubiquitin ligase neuronal cell expressed developmentally downregulated 4-2 (Nedd4
      2), which retards the retrieval of the epithelial Na+ channel ENaC. Accordingly,
      SGK1 enhances ENaC abundance in the cell membrane. The significance of this
      effect is shown by an association of an E8CC/CT;I6CC polymorphism in the SGK1
      gene with increased blood pressure. However, strong expression of SGK1 in
      enterocytes not expressing ENaC points to further functions of SGK1. This study
      was performed to test for regulation of Na+-coupled glucose transporter 1 (SGLT1)
      by Nedd4-2, SGK1, and/or the related kinases SGK3 and PKB. Additional studies
      searched for an association of the SGK1 gene with BMI. RESEARCH METHODS AND
      PROCEDURES: mRNA encoding SGLT1, wild-type Nedd4-2, inactive (C938S)Nedd4-2, wild
      type SGK1, constitutively active (S422D)SGK1 or inactive (K127N)SGK1, wild-type
      SGK3, and constitutively active (T308DS473D)PKB or inactive (T308AS473A)PKB were
      injected into Xenopus oocytes, and glucose transport was quantified from glucose
      induced current (I(glc)). BMI was determined in individuals with or without the
      E8CC/CT;I6CC polymorphism. RESULTS: I(glc) was significantly decreased by
      coexpression of Nedd4-2 but not of (C938S)Nedd4-2. Coexpression of SGK1,
      (S422D)SGK1, SGK3, or (T308DS473D)PKB, but not of (K127N)SGK1 or (T308AS473A)PKB,
      enhanced I(glc) and reversed the effect of Nedd4-2. SGK1 and SGK3 phosphorylated
      Nedd4-2. Deletion of the SGK/PKB phosphorylation sites in Nedd4-2 blunted the
      kinase effects. BMI was significantly (p < 0.008) greater in individuals with the
      E8CC/CT;I6CC polymorphism than in individuals without. DISCUSSION: Overactivity
      of SGK1 may lead not only to excessive ENaC activity and hypertension but also to
      enhanced SGLT1 activity and obesity.

PMID- 15166309
TI  - Adiponectin but not resistin is associated with insulin resistance-related
      phenotypes in baboons.
AB  - OBJECTIVE: The hormones adiponectin and resistin have been associated with
      insulin resistance. This paper analyzed the potential relationship between
      adiponectin and resistin and insulin resistance-related phenotypes in baboons.
      RESEARCH METHODS AND PROCEDURES: One hundred eight adult baboons (84 female and
      24 male) were studied. Weight was measured, and a blood sample was collected
      under fasting conditions for plasma and monocyte isolation. Fasting glucose,
      insulin, C-peptide, and adiponectin levels in plasma were measured by standard
      methods. Insulin resistance was calculated by the homeostasis model assessment
      index. Resistin mRNA abundance in monocytes was determined by real-time
      quantitative reverse transcription-polymerase chain reaction. Data were clustered
      by weight tertiles for statistical analysis. RESULTS: As observed in humans, the
      insulin resistance-related phenotypes were related to weight, plasma levels of
      adiponectin, and C-peptide. No significant relationship between resistin
      circulating levels or expression in monocytes and insulin resistance-related
      phenotypes was found in baboons. DISCUSSION: These findings suggest that resistin
      is not associated with insulin resistance. However, previous observations of
      relationships among weight, adiponectin, and insulin resistance are confirmed.

PMID- 15166311
TI  - Learning to discriminate between ligand-bound and disulfide-bound cysteines.
AB  - We present a machine learning method to discriminate between cysteines involved
      in ligand binding and cysteines forming disulfide bridges. Our method uses a
      window of multiple alignment profiles to represent each instance and support
      vector machines with a polynomial kernel as the learning algorithm. We also
      report results obtained with two new kernel functions based on similarity
      matrices. Experimental results indicate that binding type can be predicted at
      significantly higher accuracy than using PROSITE patterns.

PMID- 15166310
TI  - Obesity in insulin receptor substrate-2-deficient mice: disrupted control of
      arcuate nucleus neuropeptides.
AB  - OBJECTIVE: Disturbances in insulin signaling have been shown to induce obesity
      and/or hyperphagia in brain insulin receptor or insulin receptor substrate-2 (IRS
      2) knockout (KO) mice. This study aimed to examine the central and peripheral
      mechanisms underlying the phenotype in IRS-2 KO mice. RESEARCH METHODS AND
      PROCEDURES: We measured the histological characterization of adipose tissues,
      mRNA levels of pro-opiomelanocortin, agouti-related protein, and neuropeptide Y
      in the hypothalamus and uncoupling proteins (UCPs) in peripheral tissues of IRS-2
      KO mice. RESULTS: Female IRS-2 KO mice showed increased daily food intake. Body
      weight and adiposity were increased in both sexes, although these differences
      were more pronounced in female than in male IRS-2 KO mice. Both male and female
      IRS-2 KO mice showed decreased UCP1 mRNA expression in brown adipose tissue with
      defective thermoregulation, and UCP2 mRNA expression was increased in the white
      adipose tissue of female knockout mice. Furthermore, arcuate nucleus mRNA
      expression of pro-opiomelanocortin, was decreased in both male and female IRS-2
      KO mice, whereas expression of agouti-related protein and neuropeptide Y were
      increased in female IRS-2 KO mice. DISCUSSION: In IRS-2 KO mice, disrupted
      control of hypothalamic neuropeptide levels and UCP mRNA expression may
      contribute to the development of obesity.

PMID- 15166312
TI  - High-throughput construction method for expression vector of peptides for NMR
      study suited for isotopic labeling.
AB  - Fusion protein constructs for labeled peptides were generated with the 114 amino
      acid thioredoxin (TRX), coupled with the incorporation of a histidine tag for
      affinity purification. Two tandem AhdI sites were designed in the multiple
      cloning site of the fusion vector according to our novel unidirectional TA
      cloning methodology named PRESAT-vector, allowing one-step background-free
      cloning of DNA fragments. Constructs were designed to incorporate the four
      residue sequence Ile-Asp-Gly-Arg to generate pure peptides following Factor Xa
      cleavage of the fusion protein. The system is efficient and cost-effective for
      isotopic labeling of peptides for heteronuclear NMR studies. Seven peptides of
      varying length, including pituitary adenylate cyclase activating polypeptide
      (PACAP), vasoactive intestinal peptide (VIP) and ubiquitin interacting motif
      (UIM), were expressed using this TRX fusion system to give soluble fusion protein
      constructs in all cases. Three alternative methods for the preparation of DNA
      fragments were applied depending on the length of the peptides, such as
      polymerase chain reaction, chemical synthesis or a 'semi-synthetic method', which
      is a combination of chemical synthesis and enzymatic extension. The ability
      easily to construct, express and purify recombinant peptides in a high-throughput
      manner will be of enormous benefit in areas of biomedical research and drug
      discovery.

PMID- 15166313
TI  - Designing a metal-binding site in the scaffold of Escherichia coli KDO8PS.
AB  - KDO8PS (3-deoxy-d-manno-octulosonate-8-phosphate synthase) and DAH7PS (3-deoxy-d
      arabino-heptulosonic acid-7-phosphate synthase) enzymes catalyse analogous
      condensation reactions between phosphoenolpyruvate and arabinose 5-phosphate or
      erythrose 4-phosphate, respectively. All known DAH7PS and some of KDO8PS enzymes
      (Aquifex aeolicus KDO8PS) require a metal ion for activity whereas another class
      of KDO8PS (including Escherichia coli KDO8PS) does not. Based on sequence
      alignment of all known KDO8PS and DAH7PS enzymes, we identified a single amino
      acid residue that might define the metal dependence of KDO8PS activity. One of
      the four metal-binding residues, a cysteine, is conserved only among metal
      binding KDO8PS and DAH7PS enzymes and is replaced by an asparagine residue in
      other KDO8PS enzymes. We introduced a metal binding site into E.coli KDO8PS by a
      single N26C and a double M25P N26C mutation, which led to an increased k(cat) of
      the enzymes in the presence of activating Mn(2+) ions. The M25P N26C mutant of
      E.coli KDO8PS had a value of k(cat)/K(M) in the presence of Mn(2+) ions four
      times higher than A.aeolicus KDO8PS. KDO8PS and DAH7PS may have evolved from a
      common ancestor protein that required a divalent metal ion for activity. A non
      metal-binding KDO8PSs may have evolved from an ancestor protein that was able to
      bind Mn(2+) but no longer required Mn(2+) to function and eventually lost one of
      metal-binding residues.

PMID- 15166314
TI  - Protein design to understand peptide ligand recognition by tetratricopeptide
      repeat proteins.
AB  - Protein design aims to understand the fundamentals of protein structure by
      creating novel proteins with pre-specified folds. An equally important goal is to
      understand protein function by creating novel proteins with pre-specified
      activities. Here we describe the design and characterization of a
      tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the
      eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct,
      short-range protein-peptide interactions and of long-range electrostatic
      optimization. We demonstrate that the designed protein binds specifically to the
      desired peptide and discriminates between it and the similar C-terminal peptide
      of Hsp70.

PMID- 15166315
TI  - Understanding protein lids: structural analysis of active hinge mutants in
      triosephosphate isomerase.
AB  - The conformational switch from open to closed of the flexible loop 6 of
      triosephosphate isomerase (TIM) is essential for the catalytic properties of TIM.
      Using a directed evolution approach, active variants of chicken TIM with a
      mutated C-terminal hinge tripeptide of loop 6 have been generated (Sun,J. and
      Sampson,N.S., Biochemistry, 1999, 38, 11474-11481). In chicken TIM, the wild-type
      C-terminal hinge tripeptide is KTA. Detailed enzymological characterization of
      six variants showed that some of these (LWA, NPN, YSL, KTK) have decreased
      catalytic efficiency, whereas others (KVA, NSS) are essentially identical with
      wild-type. The structural characterization of these six variants is reported. No
      significant structural differences compared with the wild-type are found for KVA,
      NSS and LWA, but substantial structural adaptations are seen for NPN, YSL and
      KTK. These structural differences can be understood from the buried position of
      the alanine side chain in the C-hinge position 3 in the open conformation of wild
      type loop 6. Replacement of this alanine with a bulky side chain causes the
      closed conformation to be favored, which correlates with the decreased catalytic
      efficiency of these variants. The structural context of loop 6 and loop 7 and
      their sequence conservation in 133 wild-type sequences is also discussed.

PMID- 15166318
TI  - Three-dimensional polarimetric imaging of coronal mass ejections.
AB  - We present three-dimensional reconstructions of coronal mass ejections (CMEs),
      which were obtained through polarization analysis of single-view images recorded
      with the use of the Large Angle and Spectrometric Coronagraph (LASCO) C2
      coronagraph on board the Solar and Heliospheric Observatory (SOHO) spacecraft.
      Analysis of a loop-like CME shows a complex three-dimensional structure centered
      at 40 degrees from the plane of the sky, moving radially at 250
      kilometers/second. Reconstruction of two halo CMEs suggests that these events are
      expanding loop arcades.

PMID- 15166317
TI  - Control of stochasticity in eukaryotic gene expression.
AB  - Noise, or random fluctuations, in gene expression may produce variability in
      cellular behavior. To measure the noise intrinsic to eukaryotic gene expression,
      we quantified the differences in expression of two alleles in a diploid cell. We
      found that such noise is gene-specific and not dependent on the regulatory
      pathway or absolute rate of expression. We propose a model in which the balance
      between promoter activation and transcription influences the variability in
      messenger RNA levels. To confirm the predictions of our model, we identified both
      cis- and trans-acting mutations that alter the noise of gene expression. These
      mutations suggest that noise is an evolvable trait that can be optimized to
      balance fidelity and diversity in eukaryotic gene expression.

PMID- 15166316
TI  - Dissection of the mammalian midbody proteome reveals conserved cytokinesis
      mechanisms.
AB  - Cytokinesis is the essential process that partitions cellular contents into
      daughter cells. To identify and characterize cytokinesis proteins rapidly, we
      used a functional proteomic and comparative genomic strategy. Midbodies were
      isolated from mammalian cells, proteins were identified by multidimensional
      protein identification technology (MudPIT), and protein function was assessed in
      Caenorhabditis elegans. Of 172 homologs disrupted by RNA interference, 58%
      displayed defects in cleavage furrow formation or completion, or germline
      cytokinesis. Functional dissection of the midbody demonstrated the importance of
      lipid rafts and vesicle trafficking pathways in cytokinesis, and the utilization
      of common membrane cytoskeletal components in diverse morphogenetic events in the
      cleavage furrow, the germline, and neurons.

PMID- 15166319
TI  - Prostate cancer: detection of extracapsular extension by genitourinary and
      general body radiologists at MR imaging.
AB  - PURPOSE: To determine whether predictive value of endorectal magnetic resonance
      (MR) imaging findings in detection of prostate cancer extracapsular extension
      (ECE) is significantly affected by the reader's subspecialty experience.
      MATERIALS AND METHODS: In this cohort study, 344 consecutive patients with biopsy
      proved prostate cancer underwent endorectal MR imaging followed by surgery.
      Likelihood of ECE described in MR imaging reports was compared with clinical
      predictor variables. ECE was determined from the final pathologic report on
      specimens resected at surgery. Readers of MR images were classified into
      genitourinary MR imaging radiologists (n = 4) and general body MR imaging
      radiologists (n = 6). For data analysis, Wilcoxon rank sum and chi(2) tests, as
      well as receiver operating characteristic (ROC) curves and univariate and
      multivariate logistic regression analyses, were used. A difference with P <.05
      was considered significant. RESULTS: Univariate analysis results demonstrated
      that all predictors except clinical stage were significantly associated with
      detection of ECE in both groups of readers (P <.05). In the genitourinary MR
      imaging radiologist group of patients, area under the ROC curve for endorectal MR
      imaging findings (0.833) was larger than areas under the curves for all other
      predictors (0.566-0.701). In the general body MR imaging radiologist group of
      patients, area under the ROC curve for endorectal MR imaging findings (0.646) was
      not larger than areas under the curves for all other predictors (0.582-0.793).
      Results of multivariate analysis of two models, one with all predictors and
      another with all predictors except endorectal MR imaging findings, demonstrated a
      significant increase in area under the ROC curve with endorectal MR images
      interpreted by genitourinary MR imaging radiologists (P =.019 and.31,
      respectively). CONCLUSION: Endorectal MR imaging findings are significant
      predictors for detection of ECE when MR images are interpreted by genitourinary
      radiologists experienced with MR imaging of the prostate.

PMID- 15166320
TI  - Acute myocardial infarction: evaluation with first-pass enhancement and delayed
      enhancement MR imaging compared with 201Tl SPECT imaging.
AB  - PURPOSE: To evaluate acute myocardial infarction by using first-pass enhancement
      (FPE) and delayed enhancement (DE) magnetic resonance (MR) imaging compared with
      thallium 201 ((201)Tl) single photon emission computed tomography (SPECT).
      MATERIALS AND METHODS: Contrast material-enhanced FPE MR, inversion-recovery DE
      MR, and rest-redistribution (201)Tl SPECT images were obtained in 60 consecutive
      patients (53 men, seven women; mean age [+/- SD], 56 years +/- 13; range, 30-78
      years) at 6 days +/- 3 after reperfused first myocardial infarction. Presence of
      microvascular obstruction was determined on FPE MR images. Infarct size was
      defined on DE MR images as percentage of left ventricular (LV) area and compared
      with uptake defect on redistribution (201)Tl SPECT images. Differences in
      continuous data were analyzed with Student t test. Linear regression and Bland
      Altman analysis were used to compare measurements of infarct size. RESULTS: Mean
      infarct size was not significantly different between DE MR imaging (20.7% +/-
      11.5% of LV area) and (201)Tl SPECT (19.4% +/- 14.3% of LV area; P =.26); good
      correlation (r = 0.73; P <.001) and agreement were found, with a mean difference
      of +1.3% +/- 9.8% of LV area. (201)Tl SPECT failed to depict infarct in six (20%)
      of 30 patients with inferior myocardial infarction (mean size, 6.4% +/- 5.7% of
      LV area on DE MR images), whereas DE MR images showed the infarct in all patients
      (P <.01). FPE MR images depicted microvascular obstruction in 23 (38%) of 60
      patients; these patients had larger infarctions at DE MR imaging than did
      patients without microvascular obstruction (30.4% +/- 9.0% vs 15.1% +/- 8.4% of
      LV area, P <.001). (201)Tl SPECT showed larger infarcts in patients with
      microvascular obstruction (26.7% +/- 16.2% vs 15.0% +/- 11.2% of LV area, P
      <.01). CONCLUSION: Good correlation and agreement with (201)Tl SPECT indicate DE
      MR imaging may be used to estimate infarct size 6 days after reperfused acute
      myocardial infarction. DE MR imaging is more sensitive for detection of inferior
      infarction than is (201)Tl SPECT. Patients with microvascular obstruction on FPE
      MR images have larger infarcts.

PMID- 15166321
TI  - Prostate cancer: incremental value of endorectal MR imaging findings for
      prediction of extracapsular extension.
AB  - PURPOSE: To assess the incremental value of endorectal magnetic resonance (MR)
      imaging findings in addition to clinical variables for prediction of
      extracapsular extension (ECE) in patients with prostate cancer. MATERIALS AND
      METHODS: In this cohort study, 344 consecutive patients with biopsy-proved
      prostate cancer underwent endorectal MR imaging prior to surgery; 216 of these
      patients also underwent MR spectroscopic imaging. MR images were interpreted by
      10 attending radiologists. The likelihood of ECE was scored retrospectively on
      the basis of MR imaging reports. Clinical variables included serum prostate
      specific antigen (PSA) level, Gleason score, clinical stage of tumor, greatest
      percentage of cancer in all core biopsy specimens, percentage of cancer-positive
      core specimens in all core biopsy specimens, and presence of perineural invasion.
      For data analysis, receiver operating characteristic (ROC) curves and univariate
      and multivariate logistic regression analyses were used. Jackknife analysis was
      used for prediction of probability from a model that included clinical variables
      as tested comparatively with a model that included the clinical variables plus
      endorectal MR imaging findings. A difference with P <.05 was considered
      significant. RESULTS: At univariate analysis, all variables were associated with
      ECE. At ROC univariate analysis, endorectal MR imaging findings had the largest
      area under the ROC curve. At multivariate analysis, serum PSA level, percentage
      of cancer in all core biopsy specimens, and endorectal MR imaging findings (P
      =.001, P =.001, and P <.001, respectively) were predictors of ECE. Areas under
      ROC curve for two models, with and without endorectal MR imaging findings, were
      0.838 and 0.772, respectively (P =.022). CONCLUSION: A model containing
      endorectal MR imaging findings has a significantly larger area under the ROC
      curve than a model containing only clinical variables; thus, endorectal MR
      imaging findings add incremental value in the prediction of ECE.

PMID- 15166322
TI  - MR imaging of the stomach: potential use for mangafodipir trisodium--a study in
      swine.
AB  - PURPOSE: To evaluate mangafodipir trisodium as a potential contrast agent at
      magnetic resonance (MR) imaging of the stomach. MATERIALS AND METHODS:
      Mangafodipir trisodium was injected intravenously into three swine at a dose of 5
      micromol per kilogram of body weight. For comparison, gadopentetate dimeglumine
      was injected into three other swine at a dose of 0.1 mmol per kilogram of body
      weight. T1-weighted three-dimensional MR images were acquired in all six swine at
      1.5 T before and approximately 10, 15, 20, 25, 30, and 40 minutes after contrast
      material administration. Extracted stomach specimens were imaged at 3.0 T. In
      vivo and ex vivo images were evaluated visually and quantitatively for contrast
      enhancement of the stomach, and in vivo images were evaluated for the presence of
      reflux from the duodenum. RESULTS: Mangafodipir trisodium produced prolonged and
      selective enhancement of the inner surface of the stomach, in contrast to the
      more general enhancement seen with gadopentetate dimeglumine, and reflux from the
      duodenum could not account for this selective enhancement. Ex vivo images
      confirmed that T1 enhancement in the stomach wall with mangafodipir trisodium was
      limited to the inner surface. Gadopentetate dimeglumine did not produce selective
      enhancement of the inner surface of the stomach. CONCLUSION: Mangafodipir
      trisodium preferentially enhances the inner surface of the stomach on MR images
      acquired in swine and, therefore, may have potential for use as a contrast agent
      at MR imaging of the human stomach.

PMID- 15166323
TI  - Large liver tumors: protocol for radiofrequency ablation and its clinical
      application in 110 patients--mathematic model, overlapping mode, and electrode
      placement process.
AB  - PURPOSE: To establish a preoperative protocol for ultrasonographically guided
      percutaneous radiofrequency (RF) ablation of large liver tumors that is based on
      mathematic models and clinical experience and to evaluate the role of this
      protocol in RF ablation. MATERIALS AND METHODS: A regular prism and a regular
      polyhedron model were used to develop a preoperative protocol for liver tumor
      ablation. This protocol enabled the authors to minimize the number of ablation
      spheres, optimize the overlapping mode, and determine the electrode placement
      process. One hundred ten patients with 121 liver tumors were treated by using
      this protocol. Sixty-nine patients had 74 hepatocellular carcinomas (HCCs), and
      41 had 47 metastases to the liver (ie, metastatic liver carcinomas [MLCs]).
      Patients underwent follow-up helical computed tomography (CT) 1 month and every 2
      3 months after RF ablation. Ablation was considered a success if no contrast
      enhancement was detected in the treated area on the CT scan obtained at 1 month.
      RESULTS: A total of 536 ablations were performed in the 121 tumors. The ablation
      success rate was 87.6% (106 of 121 tumors); the local recurrence rate, 24.0% (29
      of 121 tumors); and the estimated mean recurrence-free survival, 17.1 months.
      Twenty-five patients underwent 38 re-treatments for local tumor recurrence. Major
      complications occurred in seven patients. Of these patients, only one, who had a
      tumor close to the colon, had a colon perforation 1 week after RF and required
      surgical intervention. CONCLUSION: The described protocol for treatment of large
      tumors had a success rate of 87.6% and a local recurrence rate of 24.0%.

PMID- 15166324
TI  - Subsequent publication of orally presented original studies within 5 years after
      1995 RSNA Scientific Assembly.
AB  - PURPOSE: To determine the rate at which original studies that were presented
      orally at the 1995 Radiological Society of North America (RSNA) Scientific
      Assembly were published in Medline-indexed journals and to identify factors
      predictive of publication. MATERIALS AND METHODS: The 1995 RSNA Scientific
      Program was jointly reviewed by two readers. A total of 1,897 abstracts were
      included in the study. A Medline search of articles published between 1996 and
      2000 was then conducted to identify articles written by the first, second, and/or
      last authors of all abstracts published in the 1995 RSNA Scientific Program. The
      year of publication, journal, country origin of the abstract, subspecialty, and
      nature of the research (ie, human, animal, or technical) were recorded.
      Publication rates were compared by using multiple logistic regression analysis.
      RESULTS: Six hundred thirty-five abstracts were expanded into manuscripts that
      were subsequently published in Medline-indexed journals; thus, the publication
      rate was 33%. A study was published less than 3 years after the 1995 scientific
      assembly in 595 (94%) cases. Genitourinary radiology and chest radiology studies
      had the highest publication rates (46% and 48%, respectively; P <.01), whereas
      physics studies had the lowest (24%, P <.001). Technical studies (24%, P <.001)
      were less likely than human studies (36%, P <.001) to be published. The
      publication rate also differed substantially according to the country origin of
      the abstract. The articles were published in a total of 109 journals and chiefly
      in Radiology (211 cases, 33% of published studies). CONCLUSION: One-third of
      original studies presented orally at the 1995 scientific assembly were
      subsequently published in Medline-indexed journals. More articles were published
      in Radiology than in any other identified journal.

PMID- 15166325
TI  - Esophagorespiratory fistula: long-term results of palliative treatment with
      covered expandable metallic stents in 61 patients.
AB  - PURPOSE: To evaluate long-term clinical results of palliative treatment of
      esophagorespiratory fistulas (ERFs) with covered expandable metallic stents.
      MATERIALS AND METHODS: Sixty patients with ERFs due to esophageal or bronchogenic
      carcinoma and one patient with ERF due to pressure necrosis caused by initial
      esophageal stent placement for esophageal carcinoma were treated with covered
      expandable esophageal or tracheobronchial metallic stents. Information about
      technical success of stent placement, initial clinical success and failure,
      fistula reopening, and complications was obtained. Survival curves for both
      patient groups with initial clinical success and failure were obtained and
      compared with Kaplan-Meier methods and log-rank test. RESULTS: Stent placement
      was technically successful in all patients, with no immediate procedural
      complications. The stent completely sealed off the fistula in 49 (80%) of 61
      patients so that they had no further aspiration symptoms (initial clinical
      success). Twelve (20%) of 61 patients had persistent aspiration symptoms due to
      incomplete ERF closure (initial clinical failure). During follow-up, the fistula
      reopened in 17 (35%) of 49 patients with initial clinical success: In eight
      patients, the reopened ERF was sealed off successfully with stent placement or
      balloon dilation. In two patients with reopened ERF caused by food impaction, the
      reopened fistula resolved spontaneously. Seven patients did not undergo further
      treatment. All patients died during follow-up, and mean survival was 13.4 weeks
      (range, 1-56 weeks) after stent placement. Mean survival in patients with initial
      clinical success was significantly longer than that in patients with initial
      clinical failure (15.1 vs 6.2 weeks, P <.05). CONCLUSION: Covered expandable
      metallic stents were placed in 61 patients with ERFs, but the initial clinical
      success rate was poor and the rate of reopening was high; however, interventional
      treatment was effective for sealing off reopened ERFs.

PMID- 15166326
TI  - Metastases in supraclavicular lymph nodes in lung cancer: assessment with
      palpation, US, and CT.
AB  - PURPOSE: To compare ultrasonography (US), computed tomography (CT), and palpation
      for diagnosing supraclavicular lung cancer metastases and to assess the effect of
      proved metastases on TNM stage and diagnostic work-up. MATERIALS AND METHODS: One
      hundred seventeen consecutive patients (91 men and 26 women; mean age, 64.0
      years) underwent palpation, US, and CT of supraclavicular regions and chest and
      upper abdominal CT. Fine-needle aspiration cytologic (FNAC) analysis was
      performed in patients with nodes with a short-axis diameter of 5 mm or greater;
      cytologic diagnosis was used as the standard of reference. Sensitivities of
      palpation, US, and CT were compared with McNemar testing. Relationship between
      size and palpability of nodes with metastasis was evaluated with logistic
      regression. RESULTS: Supraclavicular metastases were diagnosed cytologically in
      30 (26%) of 117 patients: eight (31%) of 26 patients with small cell lung cancer
      (SCLC) and 22 (24%) of 91 patients with non-small cell lung cancer (NSCLC).
      Sensitivities of US (1.00; 30 of 30 patients) and CT (0.83; 25 of 30 patients)
      for detection of metastases were significantly higher (P <.001 and P =.001,
      respectively) than that of palpation (0.33; 10 of 30 patients). Palpable nodes
      with metastasis (mean diameter, 25.2 mm) were significantly larger than
      nonpalpable nodes with metastasis (mean diameter, 13.7 mm) (P =.002). To have a
      50% chance of being palpable, nodes with metastasis had to have a diameter of at
      least 22.3 mm. TNM stage was changed in three of 91 patients with NSCLC, and
      further invasive diagnostic procedures were prevented in 11 of such patients
      because it was proved that nonpalpable nodes had metastases. CONCLUSION:
      Supraclavicular lung cancer metastases were cytologically proved in 26% of
      patients. Nodes with metastasis were only palpable when markedly enlarged. US
      tripled the sensitivity of palpation for detection of metastases. Results of US
      and US-guided FNAC analysis can change the work-up in patients with lung cancer.

PMID- 15166327
TI  - Hepatic venous congestion after living donor liver transplantation with right
      lobe graft: two-phase CT findings.
AB  - PURPOSE: To describe and determine clinical importance of two-phase computed
      tomographic (CT) findings of hepatic venous congestion after living donor liver
      transplantation (LDLT) with right lobe graft. MATERIALS AND METHODS: Forty-eight
      patients underwent two-phase (hepatic arterial phase and portal venous phase
      [PVP]) CT at 1, 2, and 4 weeks after LDLT. Images were evaluated for hepatic
      attenuation difference in areas of hepatic venous congestion, opacification of
      hepatic and peripheral portal veins in those areas, and changes in findings at
      follow-up CT. CT findings were correlated with serum bilirubin level. Fisher
      exact test and mixed model were applied. Histopathologic specimens were obtained
      in six patients. RESULTS: Thirty patients (62%) had attenuation difference in
      segments V and VIII of right lobe transplant at initial CT scanning.
      Opacification of hepatic or peripheral portal veins was seen in 17 (63%) and 27
      (100%) hyperattenuating areas of congestion during PVP and in none and three
      (19%) of 16 hypoattenuating areas, respectively. At 4-week follow-up CT,
      attenuation difference decreased in volume in 11 of 16 patients with
      hypoattenuation during PVP. All 14 patients with hyperattenuation showed no
      change in volume, but attenuation difference had decreased or disappeared.
      Histopathologic specimens showed evidence of hepatic venous congestion in all six
      patients. Hypoattenuation was seen at PVP CT in all three patients with severe
      hepatic venous congestion at histopathologic examination. Serum bilirubin level
      was significantly different between patients with hypoattenuation and those with
      hyperattenuation during PVP (P =.035) and between patients with hypoattenuation
      and those without attenuation difference (P =.009). CONCLUSION: Areas possibly
      related to hepatic venous congestion after LDLT have variable attenuation at CT;
      decreased enhancement during PVP correlates with increased postoperative serum
      bilirubin level, which indicates severity of hepatic venous congestion.

PMID- 15166328
TI  - Appendix in children with cystic fibrosis: US features.
AB  - PURPOSE: To evaluate the ultrasonographic (US) appearance of the appendix in
      children with cystic fibrosis but who were asymptomatic for appendicitis.
      MATERIALS AND METHODS: Between March 2001 and March 2002, 31 children (14 boys,
      17 girls; mean age, 9.5 years; range, 2-16 years) with cystic fibrosis underwent
      graded-compression US of the appendix. The recordings were analyzed in consensus
      by two radiologists specialized in US. The overall appendiceal diameter and
      change in diameter during graded compression, wall dimensions, contents of
      material in the lumen, and periappendicular fat were evaluated. The exclusion
      criterion was abdominal pain at the time of investigation. RESULTS: In all but
      one patient, the appendix was visualized with US. The diameter of the appendix
      ranged from 4.0 to 14.5 mm (mean, 8.3 mm). In 25 patients (83.3%), the appendix
      measured more than 6.0 mm. In six patients, the diameter of the appendix changed
      when graded compression was applied. Mucoid material was found in the lumen in 27
      of 30 patients. No wall thickening occurred, and concentric layer structures of
      the wall were intact. No involvement of the neighboring mesenteric or omental fat
      was encountered. CONCLUSION: The appendiceal diameter was enlarged in the
      majority of children examined. The lumen contained mucoid contents. Therefore,
      the diameter of the appendix alone may not be a parameter for diagnosing
      appendicitis in patients with cystic fibrosis.

PMID- 15166330
TI  - Global workforce bolsters U.S. science.

PMID- 15166329
TI  - Rheumatoid arthritis-related lung diseases: CT findings.
AB  - PURPOSE: To evaluate computed tomographic (CT) findings of rheumatoid arthritis
      related lung disease and categorize findings according to pathologic features.
      MATERIALS AND METHODS: CT scans obtained in 63 patients (27 men, 36 women; mean
      age, 61.7 years +/- 11.2 [SD]; range, 28-81 years) with rheumatoid arthritis were
      assessed. Mean duration of disease was 7.6 years +/- 9.2. Lung parenchymal
      abnormalities that included airspace consolidation, ground-glass opacity (GGO),
      reticulation, honeycombing, nodules, bronchiectasis, and air trapping were
      assessed retrospectively by two chest radiologists. Final decision was reached
      with consensus of these radiologists and a third radiologist. Patients were
      classified according to the predominant CT pattern. One of the chest radiologists
      and a pulmonary pathologist compared CT findings with pathologic findings in 17
      patients. Interobserver agreement between the first two radiologists was
      assessed. Correlation between CT finding extent score and pulmonary function test
      results was estimated with Spearman rank correlation coefficient. RESULTS: GGO
      (57 [90%] patients) and reticulation (62 [98%] patients) were the most common CT
      features. Four major CT patterns were identified: usual interstitial pneumonia (n
      = 26), nonspecific interstitial pneumonia (n = 19), bronchiolitis (n = 11), and
      organizing pneumonia (n = 5). Usual interstitial pneumonia and nonspecific
      interstitial pneumonia CT patterns overlapped; GGO was more extensive in patients
      with nonspecific interstitial pneumonia CT pattern (P =.028). In 17 patients who
      underwent biopsy, CT findings reflected pathologic findings. Exceptions were two
      patients classified with usual interstitial pneumonia at CT but with nonspecific
      interstitial pneumonia at pathologic analysis; one patient, with nonspecific
      interstitial pneumonia at CT but desquamative interstitial pneumonia at
      pathologic analysis; and one patient, with lymphoid interstitial pneumonia at CT
      but nonspecific interstitial pneumonia at pathologic analysis. CONCLUSION:
      Rheumatoid arthritis is associated with four CT patterns: usual interstitial
      pneumonia, nonspecific interstitial pneumonia, bronchiolitis, and organizing
      pneumonia. The most common CT features of rheumatoid arthritis-related lung
      disease were GGO and reticulation.

PMID- 15166331
TI  - Technology transfer: U.S. scientists faulted on biotech consulting.

PMID- 15166332
TI  - Severe acute respiratory syndrome: lab accidents prompt calls for new containment
      program.

PMID- 15166333
TI  - Conservation biology: rebels seize research team in Colombia.

PMID- 15166335
TI  - Mars exploration: ESA licks wounds, but Beagle's loss remains a mystery.

PMID- 15166334
TI  - Climate change: Russia prepares to ratify Kyoto.

PMID- 15166336
TI  - Nuclear astrophysics: new measurement of stellar fusion makes old stars even
      older.

PMID- 15166337
TI  - Mammalian biology: more genomes, but shallower coverage.

PMID- 15166339
TI  - Public health. Asthma linked to indoor dampness.

PMID- 15166338
TI  - Canada. Monsanto wins split decision in patent fight over GM crop.

PMID- 15166340
TI  - Planetary science. Saturn: the unfinished symphony.

PMID- 15166341
TI  - Francois d'Aubert interview. Bold promises, but how to deliver?

PMID- 15166342
TI  - George C. Williams profile. Stretching the limits of evolutionary biology.

PMID- 15166343
TI  - South Korea. Suddenly, science moves to the top of the government's agenda.

PMID- 15166344
TI  - Language evolution and social strata.

PMID- 15166345
TI  - The Norman conquest and the English language.

PMID- 15166346
TI  - One world scientific language?

PMID- 15166347
TI  - New EPA focus on sustainability.

PMID- 15166348
TI  - Catapults of yore.

PMID- 15166349
TI  - Ecology. Ecology for a crowded planet.

PMID- 15166350
TI  - Neuroscience. Cellular interactions in the stem cell niche.

PMID- 15166351
TI  - Developmental biology. The ups and downs of a sea anemone.

PMID- 15166352
TI  - Chemistry. Chemical topology and interlocking molecules.

PMID- 15166353
TI  - Physics. Quantum many-body effects in a single-electron transistor.

PMID- 15166354
TI  - Protein chemistry. In the footsteps of alchemists.

PMID- 15166355
TI  - Immunology. Nothing 'gainst time's scythe can make defense...

PMID- 15166358
TI  - Is the U.S. brain gain faltering?

PMID- 15166360
TI  - Are U.S. students a bellwether of quality?

PMID- 15166359
TI  - Profile: Xavier Delannay.

PMID- 15166356
TI  - Hormone therapy: physiological complexity belies therapeutic simplicity.
AB  - The results of the Women's Health Initiative, a study anticipated to provide
      definitive answers about health benefits and risks of postmenopausal hormone
      therapy, have generated debate and confusion among clinicians, researchers, and
      the lay public. The ovarian hormones estrogen and progesterone, which decline at
      menopause, normally elicit complex tissue-specific responses throughout the body.
      Major advances are providing a detailed molecular definition of how that
      differential action is achieved. Here we review estrogen and progestin actions,
      discuss how effectively knowledge of steroid hormone endocrinology has been
      incorporated into clinical studies, and consider the impact on modern hormone
      therapy protocols and pharmaceutical development.

PMID- 15166361
TI  - Profile: Rajan Gupta.

PMID- 15166363
TI  - A clearer look at Asian pollution.

PMID- 15166362
TI  - Settling in on campus.

PMID- 15166365
TI  - Profile: Alberto Saal.

PMID- 15166364
TI  - Profile: Marina Protopopova.

PMID- 15166366
TI  - Perceptions and realities of the workplace.

PMID- 15166367
TI  - A foot in each country.

PMID- 15166368
TI  - Profile: Lai-Sheng Wang.

PMID- 15166369
TI  - Profile: Roxanne Duan.

PMID- 15166370
TI  - CO2 elicits long-term decline in nitrogen fixation.

PMID- 15166371
TI  - Photon-induced Kondo satellites in a single-electron transistor.
AB  - We measure the differential conductance of a single-electron transistor (SET)
      irradiated with microwaves. The spin-entangled many-electron Kondo state produces
      a zero-bias peak in the dc differential conductance if the quantum dot in the SET
      contains an unpaired electron. When the photon energy hf is comparable to the
      energy width of the Kondo peak and to e (the charge on the electron) times the
      microwave voltage across the dot, satellites appear in the differential
      conductance shifted in voltage by +/-hf/e from the zero-bias resonance. We also
      observe an overall suppression of the Kondo features with increasing microwave
      voltage.

PMID- 15166372
TI  - High pore fluid pressure may cause silent slip in the Nankai Trough.
AB  - Silent-slip events have been detected at several subduction zones, but the cause
      of these events is unknown. Using seismic imaging, we detected a cause of the
      Tokai silent slip, which occurred at a presumed fault zone of a great earthquake.
      The seismic image that we obtained shows a zone of high pore fluid pressure in
      the subducted oceanic crust located down-dip of a subducted ridge. We propose
      that these structures effectively extend a region of conditionally stable slips
      and consequently generate the silent slip.

PMID- 15166373
TI  - Changes in Earth's reflectance over the past two decades.
AB  - We correlate an overlapping period of earthshine measurements of Earth's
      reflectance (from 1999 through mid-2001) with satellite observations of global
      cloud properties to construct from the latter a proxy measure of Earth's global
      shortwave reflectance. This proxy shows a steady decrease in Earth's reflectance
      from 1984 to 2000, with a strong climatologically significant drop after 1995.
      From 2001 to 2003, only earthshine data are available, and they indicate a
      complete reversal of the decline. Understanding how the causes of these decadal
      changes are apportioned between natural variability, direct forcing, and
      feedbacks is fundamental to confidently assessing and predicting climate change.

PMID- 15166374
TI  - Elastic behavior of cross-linked and bundled actin networks.
AB  - Networks of cross-linked and bundled actin filaments are ubiquitous in the
      cellular cytoskeleton, but their elasticity remains poorly understood. We show
      that these networks exhibit exceptional elastic behavior that reflects the
      mechanical properties of individual filaments. There are two distinct regimes of
      elasticity, one reflecting bending of single filaments and a second reflecting
      stretching of entropic fluctuations of filament length. The mechanical stiffness
      can vary by several decades with small changes in cross-link concentration, and
      can increase markedly upon application of external stress. We parameterize the
      full range of behavior in a state diagram and elucidate its origin with a robust
      model.

PMID- 15166375
TI  - A microfluidic device for conducting gas-liquid-solid hydrogenation reactions.
AB  - We have developed an efficient system for triphase reactions using a microchannel
      reactor. Using this system, we conducted hydrogenation reactions that proceeded
      smoothly to afford the desired products quantitatively within 2 minutes for a
      variety of substrates. The system could also be applied to deprotection
      reactions. We could achieve an effective interaction between hydrogen,
      substrates, and a palladium catalyst using extremely large interfacial areas and
      the short path required for molecular diffusion in the very narrow channel space.
      This concept could be extended to other multiphase reactions that use gas-phase
      reagents such as oxygen and carbon dioxide.

PMID- 15166376
TI  - Molecular borromean rings.
AB  - The realization of the Borromean link in a wholly synthetic molecular form is
      reported. The self-assembly of this link, which is topologically achiral, from 18
      components by the template-directed formation of 12 imine and 30 dative bonds,
      associated with the coordination of three interlocked macrocycles, each
      tetranucleating and decadentate overall, to a total of six zinc(II) ions, is near
      quantitative. Three macrocycles present diagonally in pairs, six exo-bidentate
      bipyridyl and six endo-diiminopyridyl ligands to the six zinc(II) ions. The use,
      in concert, of coordination, supramolecular, and dynamic covalent chemistry
      allowed the highly efficient construction, by multiple cooperative self-assembly
      processes, of a nanoscale dodecacation with an approximate diameter of 2.5
      nanometers and an inner chamber of volume 250 A(3), lined with 12 oxygen atoms.

PMID- 15166377
TI  - Multiple catenanes derived from calix[4]arenes.
AB  - A multicatenane is described in which two belts consisting of four annelated
      rings attached to the wide rims of two calix[4]arenes are interwoven in such a
      way that each ring of one belt penetrates two adjacent rings of the other belt
      and vice versa. The key step of the synthesis of this [8]catenane is the
      exclusive formation of preorganized heterodimers between a multimacrocyclic
      tetraurea calix[4]arene and an "open-chain" tetraurea calix[4]arene containing
      eight omega-alkenyl groups. When a tetraurea calix[4]arene containing four
      alkenyl groups is used, a bis-[3]catenane is formed analogously.

PMID- 15166378
TI  - Antigen bias in T cell cross-priming.
AB  - Activated CD8+ T cells detect virally infected cells and tumor cells by
      recognition of major histocompatibility complex class I-bound peptides derived
      from degraded, endogenously produced proteins. In contrast, CD8+ T cell
      activation often occurs through interaction with specialized antigen-presenting
      cells displaying peptides acquired from an exogenous cellular source, a process
      termed cross-priming. Here, we observed a marked inefficiency in exogenous
      presentation of epitopes derived from signal sequences in mouse models. These
      data indicate that certain virus- and tumor-associated antigens may not be
      detected by CD8+ T cells because of impaired cross-priming. Such differences in
      the ability to cross-present antigens should form important considerations in
      vaccine design.

PMID- 15166379
TI  - CD8+ T cell cross-priming via transfer of proteasome substrates.
AB  - "Cross-priming" describes the activation of naive CD8+ T cells by professional
      antigen-presenting cells that have acquired viral or tumor antigens from "donor"
      cells. Antigen transfer is believed to be mediated by donor cell-derived
      molecular chaperones bearing short peptide ligands generated by proteasome
      degradation of protein antigens. We show here that cross-priming is based on the
      transfer of proteasome substrates rather than peptides. These findings are
      potentially important for the rational design of vaccines that elicit CD8+ T cell
      responses.

PMID- 15166380
TI  - A family with severe insulin resistance and diabetes due to a mutation in AKT2.
AB  - Inherited defects in signaling pathways downstream of the insulin receptor have
      long been suggested to contribute to human type 2 diabetes mellitus. Here we
      describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a
      family that shows autosomal dominant inheritance of severe insulin resistance and
      diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted
      insulin signaling to metabolic end points and inhibited the function of
      coexpressed, wild-type AKT. These findings demonstrate the central importance of
      AKT signaling to insulin sensitivity in humans.

PMID- 15166382
TI  - Lacunar infarction: embolism is the key: against.

PMID- 15166384
TI  - Lacunar infarction: embolism is the key.

PMID- 15166385
TI  - Why lacunar syndromes are different and important.

PMID- 15166386
TI  - Remote evaluation of acute ischemic stroke in rural community hospitals in
      Georgia.
AB  - BACKGROUND AND PURPOSE: Despite Food and Drug Administration approval of tissue
      type plasminogen activator (tPA) for stroke, obstacles in the US health care
      system prevent widespread use. The Remote Evaluation for Acute Ischemic Stroke
      (REACH) program was developed to address these obstacles in rural settings. We
      have previously shown the reliability of the REACH system in performing a valid
      National Institutes of Health Stroke Scale (NIHSS) evaluation at the Medical
      College of Georgia (MCG). We now report on the performance of the system since
      its deployment in 5 rural hospitals in east Georgia. METHODS: The rural emergency
      department (ED) staff can activate a Code REACH protocol 24 hours per day, 7 days
      per week by calling the Emergency Communications Center (ECC, an in-house
      dispatch center) at MCG, who pages the on-call consultant. The consultant calls
      back the ECC and is connected to the waiting ED. Simultaneously, using any
      broadband-connected workstation, the consultant logs in to the REACH system,
      allowing performance of an NIHSS evaluation, review of the computerized
      tomography (CT) images transmitted by the local radiology staff, and then the
      consultant can speak to the patient and family to verify time of onset. RESULTS:
      The REACH system has evaluated 75 patients from March 2003 to April 2004, and 12
      have received tPA, all without intracranial hemorrhage complications. NIHSS
      scores ranged from 0 to 30, with a mean of 14.3 (SD=8.7, median 11.5). The mean
      onset to door time was 70.9 minutes (SD=70.8, median 50), the mean door to
      consult time was 45.1 minutes (SD=39.8, median 34), and the mean door to NIHSS
      completion was 62.9 minutes (SD=50.8, median 51). The mean onset to needle time
      was 135.33 minutes (SD=51.45, median 134.5). CONCLUSIONS: The REACH system
      enables remote stroke physicians to direct the local ED staff to administer tPA
      in rural settings where thrombolytics were not previously used. REACH may be used
      as a rapid consult tool to provide the same quality of stroke care to patients in
      rural hospitals as is given in tertiary stroke centers. This supports our
      endeavor to bring stroke expertise to rural community hospitals.

PMID- 15166387
TI  - Association between cerebral ischemia and cytotoxin-associated gene-A-bearing
      strains of Helicobacter pylori.
AB  - BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of
      ischemic stroke yielded variable results. Infection with more virulent H. pylori
      strains, such as cytotoxin-associated gene-A (CagA)-bearing strains, may be of
      particular relevance for ischemic diseases. We investigated whether H. pylori and
      CagA seropositivity are independent risk factors for cerebral ischemia or its
      etiologic subtypes. METHODS: We determined IgG antibodies against H. pylori and
      CagA protein (enzyme immunoassays) in 190 patients with acute cerebral ischemia
      and in 229 age- and sex-matched control subjects selected randomly from the
      general population. RESULTS: CagA seropositivity was more common in patients
      (114/190; 60.0%) than in control subjects (99/229; 43.2%; odds ratio, 1.97; 95%
      CI, 1.33 to 2.91; P<0.001). This result remained significant after adjustment for
      age, sex, vascular risk factors and diseases, and childhood and adult social
      status (odds ratio, 1.84; 95% CI, 1.13 to 3.00; P=0.015). Subgroup analyses
      yielded similar results in all etiologic stroke subtypes. In contrast, H. pylori
      seropositivity in general was not associated with increased risk of stroke or its
      etiologic subtypes. CONCLUSIONS: Our results support the hypothesis of an
      association between infection with CagA-positive H. pylori strains and acute
      cerebral ischemia.

PMID- 15166388
TI  - Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar
      infarction.
AB  - BACKGROUND AND PURPOSE: There is growing evidence that pharmacologic interference
      with the renin-angiotensin system may reduce risk of stroke, although the
      mechanism is unclear. Impaired reactivity of cerebral vessels has recently been
      recognized as a risk factor for stroke. We examined the effect of the angiotensin
      converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to
      acetazolamide in patients with lacunar cerebral infarction. METHODS: We studied a
      cohort of male patients between 3 and 12 months after lacunar infarction
      confirmed on computed tomography. Each patient received perindopril 4 mg daily or
      matching placebo for 2 weeks in a randomized, double-blind, placebo-controlled
      crossover fashion. A 1-week washout period was observed between dosing periods.
      Cerebral vasomotor reactivity (increase in middle cerebral artery mean flow
      velocity in response to intravenous injection of 15 mg/kg acetazolamide) was
      measured before and after each dosing period using standard Doppler ultrasound
      techniques. RESULTS: Twelve patients (mean age 63.2+/-2.3 years) completed the
      protocol. There was no treatment order effect. Cerebral vasomotor reactivity was
      significantly greater after perindopril treatment (percent change from baseline
      +18.8+/-10.1% after perindopril, -4.6+/-4.1% after placebo; P=0.032). Dosing with
      perindopril did not affect resting cerebral blood flow velocity (percent change
      from baseline +3.1+/-9.5% after perindopril, -0.6+/-5.4% after placebo), nor was
      there a change in resting blood pressure (+1.8 mm Hg+/-3.1 after perindopril,
      +1.4 mm Hg+/-2.5 after placebo). CONCLUSIONS: This study provides evidence of a
      significant improvement in cerebral vasomotor reactivity induced by perindopril,
      beyond any effect on blood pressure. The results suggest a possible mechanism for
      the beneficial effect of ACE inhibition on stroke risk observed in recent
      clinical trials, and suggest a role for the renin-angiotensin axis in the
      pathophysiology of subcortical small vessel disease.

PMID- 15166389
TI  - Cigarette smoking as a risk factor for stroke death in Japan: NIPPON DATA80.
AB  - BACKGROUND AND PURPOSE: Some previous Japanese cohort studies failed to show an
      association between smoking and stroke risk. Because such an association has been
      noted in other populations, this issue should be re-examined in a recent
      representative Japanese cohort with a higher total cholesterol level. METHODS: A
      total of 9638 men and women aged 30 years and older without a history of
      cardiovascular disease (CVD) at baseline in 1980 were followed-up for 14 years.
      RESULTS: We observed 203 stroke deaths (107 cerebral infarctions, 45 cerebral
      hemorrhages, and 51 others), 191 heart disease deaths, and 413 CVD deaths. The
      average serum total cholesterol level was approximately 4.91 mmol/L. Cox
      proportional hazard ratios were calculated adjusting for age, systolic blood
      pressure, and other conventional risk factors. The hazard ratios for men who
      smoked 1 to 20 cigarettes/day for all strokes, cerebral infarction, and cerebral
      hemorrhage were 1.60 (95% CI, 0.91 to 2.79), 2.97 (CI, 1.27 to 6.98), and 0.42
      (CI, 0.16 to 1.09), respectively, and for those who smoked > or =21
      cigarettes/day, they were 2.17 (CI, 1.09 to 4.30), 3.26 (CI, 1.11 to 9.56), and
      0.68 (CI, 0.20 to 2.33), respectively. For women who smoked > or =21
      cigarettes/day, the hazard ratio for all strokes was 3.91 (CI, 1.18 to 12.90).
      For CVD, all heart disease, and ischemic heart disease, the hazard risks of
      smoking were significant (1.49 to 4.25) for men but not significant for women.
      CONCLUSIONS: Smoking in a cohort with moderate serum total cholesterol level was
      a potent risk factor for stroke, especially cerebral infarction, for both men and
      women, and for CVD and ischemic heart disease for men.

PMID- 15166390
TI  - Venous drainage in perimesencephalic hemorrhage.
AB  - BACKGROUND AND PURPOSE: In perimesencephalic nonaneurysmal hemorrhage (PMH),
      subarachnoid blood accumulates around the midbrain. Clinical and radiological
      characteristics suggest a venous origin of PMH. We compared the venous drainage
      of the midbrain between patients with PMH and aneurysmal subarachnoid hemorrhage
      (aSAH) by means of computed tomography angiography (CTA). METHODS: CTAs of 55 PMH
      patients and 42 aSAH patients with a posterior circulation aneurysm were
      reviewed. Venous drainage was classified into: (1) normal continuous: the basal
      vein of Rosenthal is continuous with the deep middle cerebral vein and drains
      mainly to the vein of Galen (VG); (2) normal discontinuous: drainage anterior to
      uncal veins and posterior to VG; and (3) primitive variant: drainage to other
      veins than VG. Additionally, we compared in PMH patients the side of the
      primitive variant and side of the bleeding. RESULTS: A primitive variant was
      present on one or both hemispheres in 53% of PMH patients with PMH (95% CI, 40%
      to 65%) and in 19% of aSAH patients (95% CI, 10% to 33%). In all 16 PMH patients
      with a unilateral primitive drainage, blood was seen on the side of the primitive
      drainage (100%; 95% CI, 81% to 100%); blood was never found mainly on the side
      with normal drainage. CONCLUSIONS: Patients with PMH have a primitive venous
      drainage directly into dural sinuses instead of via the vein of Galen more often
      than do controls. Moreover, the side of the perimesencephalic hemorrhage relates
      to the side of the primitive drainage. These results further support a venous
      origin of PMH.

PMID- 15166391
TI  - Plasma cellular-fibronectin concentration predicts hemorrhagic transformation
      after thrombolytic therapy in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Elevated plasma levels of cellular fibronectin (c-Fn)
      reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in
      cerebral ischemia. We investigated whether high plasma levels of c-Fn were
      associated with hemorrhagic transformation (HT) after treatment with tissue
      plasminogen activator (tPA) in patients with acute stroke. METHODS: Eighty-seven
      patients (mean age: 67+/-12) received tPA after the ECASS II criteria (mean time
      to infusion: 160+/-46 minutes; median NIHSS: 12). HT and hypodensity volume were
      studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT
      was classified according to the ECASS II definitions. c-Fn and matrix
      metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples
      obtained before treatment and in 30 healthy subjects. RESULTS: HT was found in 26
      patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2,
      and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7,
      4.2, 5.4, and 7.3 microg/mL in controls, non-HT, HI-1, HI-2, and PH groups,
      respectively (P<0.001); median MMP-9 values were 54, 87, 154, 176, and 225 ng/mL
      (P<0.001). Logistic regression analysis showed that only c-Fn plasma levels
      remained independently associated with HT after adjusting for potential
      confounders (OR, 2.1; 95% CI, 1.3 to 3.4; P=0.002). Similar results were obtained
      in the 71 patients treated within 3 hours. CONCLUSIONS: High plasma c-Fn levels
      are significantly associated with subsequent HT in stroke patients treated with
      tPA, so plasma c-Fn determinations might be useful in clinical practice to
      improve the risk/benefit ratio of thrombolytic treatment.

PMID- 15166392
TI  - II genotype of the angiotensin-converting enzyme gene increases the risk for
      subarachnoid hemorrhage from ruptured aneurysm.
AB  - BACKGROUND AND PURPOSE: Evidence exists in support of a role of genetic factors
      in susceptibility to aneurysmal subarachnoid hemorrhage (SAH) in humans. Meta
      analysis of 2 previous studies showed that the I allele of angiotensin-converting
      enzyme (ACE) gene insertion/deletion (I/D) polymorphism was a weak, but
      significant, risk factor for aneurysmal SAH. Moreover, a recent study has shown
      that the local renin-angiotensin system (RAS) is involved in the development of
      intracranial aneurysm. The aim of this study was to investigate the association
      between ACE I/D polymorphism and a risk for aneurysmal SAH in a Polish
      population. METHODS: Ninety patients with aneurysmal SAH (mean age: 48.9+/-14.0
      years) and 128 healthy controls matched for age and sex were genotyped for the
      ACE I/D polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography
      and/or lumbar puncture and digital subtraction angiography. ACE gene polymorphism
      was detected by polymerase chain reaction amplification of the intron 16-specific
      I/D fragments, 490-bp and 190-bp, respectively. RESULTS: The ACE genotype
      distribution in patients with aneurysmal SAH (II, 52.2%; ID, 15.6%; DD, 32.2%)
      differed significantly from controls (II, 23.4%; ID, 50.8%; DD, 25.8%) (P<0.001).
      A logistic regression model showed that the II genotype of ACE gene was
      independent from female sex and smoking as a risk factor for aneurysmal SAH (OR,
      4.57; 95% CI, 2.35 to 8.90). CONCLUSIONS: Here we report that II genotype of ACE
      gene is a risk factor for aneurysmal SAH.

PMID- 15166393
TI  - HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery,
      suppressing acute inflammatory reaction after experimental intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Statins have neuroprotective effects on ischemic stroke.
      They modify the endothelial function, increase blood flow, and inhibit thrombus
      formation, which are independent of lipid-lowering effects. However, whether
      statins have a protective effect toward hemorrhagic stroke is yet unknown. To
      test this possibility, we attempted to determine the effect of atorvastatin on
      experimental intracerebral hemorrhage (ICH). METHODS: ICH was induced using
      stereotaxic infusion of collagenase into the left basal ganglia in adult rats.
      Atorvastatin (1 mg/kg or 10 mg/kg) or phosphate-buffered saline was administered
      for 2 weeks. To monitor the sensorimotor deficits, limb placing and Rotorod tests
      were performed. Hematoma volume, brain water content, and hemispheric atrophy
      were analyzed. Immunohistochemical staining for myeloperoxidase (MPO), microglia
      (OX42), inducible nitric oxide synthase (iNOS), or endothelial nitric oxide
      synthase (eNOS) was performed. Perihematomal cell death was determined by TUNEL
      staining. RESULTS: The atorvastatin-treated ICH group showed better performance
      on Rotorod and limb placing tests when compared with the vehicle-treated group
      (P<0.01). The hematoma volumes between groups were not different, but the brain
      water content and hemispheric atrophy were reduced in the atorvastatin-treated
      ICH group. Atorvastatin reduced TUNEL-positive cells, iNOS expression, and MPO
      positive or OX42-positive cells in the perihematomal regions in a dose-dependent
      manner, whereas it increased eNOS expression. CONCLUSIONS: The present study
      shows that atorvastatin reduces the perihematomal cell death via
      antiinflammation, which is associated with sensorimotor recovery after
      experimental ICH.

PMID- 15166395
TI  - Seizures and epilepsy after ischemic stroke.
AB  - BACKGROUND: Although a long-recognized clinical phenomenon, there remain many
      questions regarding the epidemiology of seizures and epilepsy after ischemic
      stroke, their effect on outcome, and their treatment. SUMMARY OF REVIEW:
      Interpretation of the various studies that have been conducted of postischemic
      stroke seizures and epilepsy are complicated by their heterogeneous designs,
      inconsistent uses of terminology, small sample sizes, different periods of follow
      up, and ambiguities in seizure identification and classification. Estimates of
      the rate of early postischemic stroke seizures range from 2% to 33%. The rates of
      late seizures vary from 3% to 67%. The rate of postischemic stroke epilepsy is
      approximately 2% to 4% and is higher in those who have a late seizure. Data
      reflecting seizure subtypes are limited. Aside from cortical location and,
      possibly, stroke severity, no other risk factors for postischemic stroke seizures
      have been consistently demonstrated. CONCLUSIONS: Much additional work is needed
      to better understand the epidemiology and social impact of postischemic stroke
      seizures and epilepsy, their prevention, and optimal management.

PMID- 15166394
TI  - In vivo detection of macrophages in human carotid atheroma: temporal dependence
      of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI.
AB  - Background- It has been suggested that inflammatory cells within vulnerable
      plaques may be visualized by superparamagnetic iron oxide particle-enhanced MRI.
      The purpose of this study was to determine the time course for macrophage
      visualization with in vivo contrast-enhanced MRI using an ultrasmall
      superparamagnetic iron oxide (USPIO) agent in symptomatic human carotid disease.
      METHODS: Eight patients scheduled for carotid endarterectomy underwent
      multisequence MRI of the carotid bifurcation before and 24, 36, 48, and 72 hours
      after Sinerem (2.6 mg/kg) infusion. RESULTS: USPIO particles accumulated in
      macrophages in 7 of 8 patients given Sinerem. Areas of signal intensity
      reduction, corresponding to USPIO/macrophage-positive histological sections, were
      visualized in all 7 of these patients, optimally between 24 and 36 hours,
      decreasing after 48 hours, but still evident up to 96 hours after infusion.
      CONCLUSIONS: USPIO-enhanced MRI of carotid atheroma can be used to identify
      macrophages in vivo. The temporal change in the resultant signal intensity
      reduction on MRI suggests an optimal time window for the detection of macrophages
      on postinfusion imaging.

PMID- 15166396
TI  - Longitudinal risk of intracranial hemorrhage in patients with arteriovenous
      malformation of the brain within a defined population.
AB  - BACKGROUND AND PURPOSE: Accurate estimates for risk and rates of intracranial
      hemorrhage (ICH) in the natural course of patients harboring brain arteriovenous
      malformation (BAVM) are needed to provide a quantitative basis for planning
      clinical trials to evaluate interventional strategies and to help guide practice
      management. METHODS: We identified patients with BAVM at the Kaiser Permanente
      Northern California health maintenance organization and documented their clinical
      course. The influences of age at diagnosis, gender, race-ethnicity, ICH at
      presentation, venous draining pattern, and BAVM size on ICH subsequent to
      presentation were studied using the multivariate Cox proportional hazards model
      and Kaplan-Meier curves. RESULTS: We identified 790 patients with BAVM (51%
      female; 63% white; mean age+/-SD at diagnosis: 38+/-19 years) between 1961 and
      2001. Patients who presented with ICH experienced a higher rate of subsequent ICH
      than those who presented without ICH under multivariate analysis (hazard ratio,
      3.6; 95% CI, 1.1 to 11.9; P<0.032). The effect was similar across race-ethnicity
      and gender. This difference in ICH rates was greatest in the first year (7%
      versus 3% per year) and converged over time. The effect of subsequent ICH on
      functional status was similar to that of the initial ICH. CONCLUSIONS:
      Presentation with ICH was the most important predictor of future ICH, confirming
      previous studies. Future ICH had similar impact on functional outcome as incident
      ICH. Intervention to prevent ICH would be of potentially greater benefit to
      patients presenting with ICH, although the advantage decreases over time.

PMID- 15166397
TI  - Animal protein, animal fat, and cholesterol intakes and risk of cerebral
      infarction mortality in the adult health study.
AB  - BACKGROUND AND PURPOSE: A traditional diet that is poor in animal products is
      thought to explain the high rate of stroke in Asian populations. The purpose of
      the present study was to examine the effect of a diet rich in animal protein,
      animal fat, and cholesterol on the risk of cerebral infarction mortality in a
      Japanese population. METHODS: A prospective study of 3731 Japanese men and women
      aged 35 to 89 years was conducted from 1984 to 2001. Nutrient intake was
      estimated at baseline from the responses to a 24-hour diary. During the follow-up
      period, cases of cerebral infarction deaths (as entered on death certificates)
      were monitored. RESULTS: During the follow-up period, 60 deaths were attributed
      to cerebral infarction. A high intake of animal fat and cholesterol was
      significantly associated with a reduced risk of cerebral infarction death. The
      risk was reduced by 62% (CI, 82% to 18%) for those in the third tertile of animal
      fat intake, compared with those in the first tertile, with a significant linear
      dose-response relationship (P=0.0073). The risk of death from infarction was
      reduced by 63% (CI, 82% to 22%) in the high cholesterol consumption group,
      compared with the low consumption group. A significant linear dose-response
      relationship was observed. Animal protein was not significantly associated with
      infarction mortality after adjustment for animal fat and cholesterol.
      CONCLUSIONS: This study suggests that in Japan, where animal product intake is
      lower than in Western countries, a high consumption of animal fat and cholesterol
      was associated with a reduced risk of cerebral infarction death.

PMID- 15166398
TI  - Doxycycline suppresses cerebral matrix metalloproteinase-9 and angiogenesis
      induced by focal hyperstimulation of vascular endothelial growth factor in a
      mouse model.
AB  - BACKGROUND AND PURPOSE: A number of central nervous system (CNS) disorders are
      associated with abnormalities in or activation of angiogenesis, including
      vascular malformations. To test the hypothesis that the nonspecific matrix
      metalloproteinase (MMP) inhibitor, doxycycline, suppresses vascular endothelial
      growth factor (VEGF)-induced cerebral angiogenesis through inhibition of MMPs, we
      used a mouse model with enhanced cerebral angiogenesis induced by focal
      hyperstimulation of VEGF from adenovirus DNA (AdVEGF) transduction. METHODS: The
      time course study of MMP activity was performed at 7 and 14 days after AdVEGF
      transduction. MMP activity and expression were examined by zymography and
      immunohistochemistry, respectively. As an index of cerebral angiogenesis,
      microvessel counting was performed in the brains of 3 groups of mice (n=6): (1)
      control; (2) AdVEGF only; and (3) AdVEGF plus doxycycline (30 mg/kg per day).
      RESULTS: Brain MMP-9 activities increased 4-fold (883+/-137 versus 179+/-179; 1
      sided P<0.001) at 7 days after AdVEGF transduction. VEGF transduction increased
      vessel counts by 19% (255+/-27 versus 215+/-15, 1-sided P<0.01). Doxycycline
      treatment decreased MMP-9 activity (89+/-72 versus 883+/-137; 1-sided P<0.001)
      and cerebral microvessel number (231+/-17 versus 255+/-27; 1-sided P<0.05).
      CONCLUSIONS: Doxycycline is effective in decreasing stimulated cerebral MMP-9
      activity and parenchymal angiogenesis. The decrease in MMP-9 activity is
      associated with decreased microvessel counts. Brain pathophysiological processes
      that involve abnormally enhanced angiogenesis may be amenable to manipulation by
      MMP inhibitors, including tetracycline derivatives.

PMID- 15166399
TI  - Endocrine disruptors (environmental estrogens) enhance autoantibody production by
      B1 cells.
AB  - Accumulating data suggest that endocrine disruptors affect not only the
      reproductive system, but also the immune system. We demonstrate here that
      endocrine disruptors including diethylstilbestrol (DES) and bisphenol-A (BPA)
      enhance autoantibody production by B1 cells both in vitro and in vivo. BWF1 mice,
      a murine model for systemic lupus erythematosus (SLE), implanted with Silastic
      tubes containing DES after orchidectomy developed murine lupus characterized by
      immunoglobulin G (IgG) anti-DNA antibody production and IgG deposition in the
      glomeruli in the kidney as well as those implanted with 17beta-estradiol (E2).
      Plaque-forming cells (PFC) producing autoantibodies specific for bromelain
      treated red blood cells were significantly increased in mice implanted with DES
      and BPA. IgM antibody production by B1 cells in vitro was also enhanced in the
      presence of endocrine disruptors including DES and BPA. Estrogen receptor (ER)
      expression was upregulated in B1 cells in aged BWF1 mice that developed lupus
      nephritis. These results suggest that endocrine disruptors are involved in
      autoantibody production by B1 cells and may be an etiologic factor in the
      development of autoimmune diseases.

PMID- 15166401
TI  - World Stroke Day.

PMID- 15166400
TI  - Development and characterization of a cell line that stably expresses an estrogen
      responsive luciferase reporter for the detection of estrogen receptor agonist and
      antagonists.
AB  - Recently several advisory committees (EDSTAC, ICCVAM) have recommended that
      stable estrogen-dependent gene expression assays be developed for screening
      chemicals for estrogenic activity because of the high degree of specificity of
      the response and potential for use in a high-throughput mode. In this paper we
      describe a specific, sensitive assay developed for screening chemicals for
      estrogenic and antiestrogenic activities. T47D human breast cancer cells, which
      naturally express estrogen receptor (ER) alpha and beta, were stably transfected
      with a triplet ERE (estrogen-responsive elements)-promoter-luciferase reporter
      gene construct. The transformed cells were named T47D-KBluc. These cells are
      sensitive to the potent estrogens, 17beta-estradiol, ethynyl estradiol, and
      diethylstibesterol, and well-characterized weaker environmental estrogens like
      genistein, HPTE (an estrogenic pesticide metabolite), and 4-nonylphenol. The EC50
      for estradiol was about 0.01 nM, reaching maximal induction at 0.1 nM. The
      antiestrogen, ICI 182,780, was able to completely inhibit the induction of
      luciferase expression by 0.1 nM estradiol at 10 nM, with an IC50 of 1 nM. In
      addition, we were able to replicate, in this in vitro assay, the observation that
      low concentrations of cadmium were able to induce estrogen-dependent gene
      expression, an effect that was completely inhibited by the potent antiestrogen
      ICI 182,780. The potent glucocorticoid receptor agonist, dexamethasone, was
      without effect as an ER agonist at concentrations up to 10 nM, whereas the potent
      androgen, dihydrotestosterone (DHT), showed no induction at concentration of 50
      microM, but was a partial agonist at high concentrations of 0.2 mM and above. In
      summary, we have developed a specific, sensitive estrogen-responsive gene
      expression assay in a stable cell line that could possibly be adapted for high
      throughput screening of large numbers of chemicals for estrogenic and
      antiestrogenic activity. In addition, herein we also provide key protocol
      recommendations necessary to identify and eliminate common problems encountered
      in in vitro screening for estrogenicity.

PMID- 15166402
TI  - Editorial comment--dementia after stroke.

PMID- 15166403
TI  - Editorial comment--what can models teach us about stroke treatment? Sorting out
      the missing bits.

PMID- 15166404
TI  - Improving quality of care through disease management: principles and
      recommendations from the American Heart Association's Expert Panel on Disease
      Management.

PMID- 15166405
TI  - Hyperinsulinemia and estrogen-deficiency as risk factors for stroke in women.

PMID- 15166406
TI  - Major ongoing stroke trials.

PMID- 15166416
TI  - The cell cycle and how it is steered by Kaposi's sarcoma-associated herpesvirus
      cyclin.
AB  - A timely coordination of cellular DNA synthesis and division cycles is governed
      by the temporal and spatial activation of cyclin-dependent kinases (Cdks). The
      primary regulation of Cdk activation is through binding to partner cyclin
      proteins. Several gammaherpesviruses encode a viral homologue of cellular cyclin
      D, which may function to deregulate host cell cycle progression. One of these is
      encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and is called K cyclin
      or viral cyclin (v-cyclin). v-Cyclin is expressed in most of the malignant cells
      that are associated with KSHV infection in humans, labelling v-cyclin as a
      putative viral oncogene. Here are described some of the major structural and
      functional properties of mammalian cyclin/Cdk complexes, some of which are
      phenocopied by v-cyclin. In addition, the molecular events leading to orderly
      progression through the G(1)/S and G/M cell cycle phases are reviewed. This
      molecular picture serves as a platform on which to explain v-cyclin-specific
      functional properties. Interesting but largely speculative issues concern the
      interplay between v-cyclin-mediated cell cycle deregulation and molecular
      progression of KSHV-associated neoplasms.

PMID- 15166417
TI  - A naturally occurring C-terminal truncated isoform of the latent nuclear antigen
      of Kaposi's sarcoma-associated herpesvirus does not associate with viral episomal
      DNA.
AB  - The latency-associated nuclear antigen (LANA) encoded by orf73 of Kaposi's
      sarcoma-associated herpesvirus (KSHV) binds to viral episomal DNA and nuclear
      heterochromatin in infected cells. A 3.2 kb transcript in KSHV-positive primary
      effusion lymphoma (PEL) cells (BCP-1 and BC-3) encoding a C-terminal truncated
      form of LANA (LANA-Delta76) has been identified. This transcript has the addition
      of a poly(A) tail at nt 3264 of orf73 resulting in an in-frame stop codon (TAA)
      effectively truncating LANA by 76 aa ( approximately 8 kDa). Examination of the
      coding region revealed the presence of a non-canonical polyadenylation signal
      (AGTAAA) 17 nt upstream of the poly(A) tail. The protein expressed from this
      transcript is representative of the faster migration of the LANA doublet bands
      observed by SDS-PAGE and Western blot. Mutation of the poly(A) signal from AGTAAA
      to TGTACA produced a protein that co-migrated with the larger LANA isoform. A C
      terminal LANA-Delta76 EGFP fusion protein localized to the nucleus but did not co
      localize with endogenous LANA in BCP-1 cells, or heterochromatin in HEK293 cells.
      Using an electrophoretic mobility shift assay (EMSA), the authors were able to
      show that LANA-Delta76 does not bind to the KSHV terminal repeat motif known to
      interact with LANA. These data provide evidence for the presence of an isoform of
      LANA that may perform alternative functions in KSHV-infected cells.

PMID- 15166418
TI  - Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA
      interference.
AB  - Epstein-Barr virus (EBV) reactivation into the lytic cycle plays certain roles in
      the development of EBV-associated diseases, so an effective strategy to block the
      viral lytic cycle may be of value to reduce the disease risk or to improve the
      clinical outcome. This study examined whether the EBV lytic cycle could be
      inhibited using RNA interference (RNAi) directed against the essential viral gene
      Zta. In cases of EBV reactivation triggered by chemicals or by exogenous Rta, Zta
      targeted RNAi prevented the induction of Zta and its downstream genes and further
      blocked the lytic replication of viral genomes. This antiviral effect of RNAi was
      not likely to be mediated by activation of the interferon pathway, as
      phosphorylation of STAT1 was not induced. In addition, novel EBV-infected
      epithelial cells showing constitutive activation of the lytic cycle were cloned;
      such established lytic infection was also suppressed by Zta-targeted RNAi. These
      results indicate that RNAi can be used to inhibit the EBV lytic cycle effectively
      in vitro and could also be of potential use to develop anti-EBV treatments.

PMID- 15166419
TI  - p16(INK4A)-independence of Epstein-Barr virus-induced cell proliferation and
      virus latency.
AB  - Epstein-Barr virus (EBV) has the ability to promote cell cycle progression
      following the initial infection of primary resting B-lymphocytes and to cause
      cell cycle arrest at the onset of the viral replicative cycle. Various mechanisms
      have been proposed for the proliferative effects, including the up-regulation of
      cyclin D2 by the viral EBNA-2 and EBNA-LP proteins, direct binding of EBNA3C to
      the retinoblastoma protein (pRb), and down-regulation of the p16(INK4A) tumour
      suppressor by the viral LMP1 product. To try to gain insight into the relative
      importance of these mechanisms, the ability of EBV to immortalize lymphocytes
      from an individual who is genetically deficient for p16(INK4A) was examined. From
      detailed analyses of the resultant lymphoblastoid cell lines it is concluded that
      p16(INK4A) status has little bearing on EBV's ability to manipulate the cell
      cycle machinery and a model to accommodate the previously proposed routes taken
      by EBV to bypass the restriction point is presented.

PMID- 15166420
TI  - Single-nucleotide polymorphisms in two Marek's disease virus genes (Meq and gD):
      application to a retrospective molecular epidemiology study (1982-1999) in
      France.
AB  - Marek's disease virus (MDV) is a herpesvirus that causes a lymphoproliferative
      disease in chickens. Vaccines against MDV are available, but the virus is
      gradually becoming more virulent. A molecular epidemiology study of MDV was
      carried out by assessing nucleotide variation in two different genes, Meq and gD,
      in 68 French field isolates circulating from 1982 to 1999, compared with
      reference strains. Viral DNA was amplified by nested PCR and sequenced directly.
      Comparison of the nucleotide sequences revealed a high nucleotide sequence
      identity (98 %). Single-nucleotide polymorphisms were identified, leading to the
      identification of three gene alleles for gD and six for Meq. Nine combinations of
      alleles were identified. A majority of French isolates (60.5 %) clustered in the
      C1 type, which has been present for over 17 years. Waves of non-C1-type isolates
      appeared when vaccine efficacy decreased. Furthermore, specific discriminating
      sequences were obtained for the CVI-988 vaccine strain.

PMID- 15166421
TI  - Identification of a region of the virus genome involved in murine
      gammaherpesvirus 68-induced splenic pathology.
AB  - Infection with the murine gammaherpesvirus MHV-68 has profound effects on splenic
      and mediastinal lymph node pathology in mice which lack the interferon-gamma
      receptor (IFN-gamma R(-/-)). In these mice MHV-68 infection causes fibrosis and
      loss of lymphocytes in the spleen and the mediastinal lymph node as well as
      interstitial pulmonary fibrosis and fibrotic changes in the liver. The changes
      are associated with transient elevated latent virus loads in the spleen. Four
      independent virus mutants with insertions and/or deletions in the left end of the
      genome fail to induce the pathological changes and establish latency at normal
      levels in the spleen. The data indicate that the pathology does not correlate
      with any of the known genes encoded within this region of the genome, genes M1-M4
      and the eight vtRNAs. Northern analysis of mRNAs transcribed by wild-type and
      mutant viruses shows that at least two uncharacterized transcripts are encoded
      within this region. These transcripts are absent in the mutant viruses and are
      candidates for the virus genes responsible for the aberrant pathology in IFN
      gamma R(-/-) mice.

PMID- 15166422
TI  - A new member of the interleukin 10-related cytokine family encoded by a poxvirus.
AB  - Poxviruses express numerous proteins involved in manipulating the host immune
      response. Analysis of the primary sequence and predicted structure of the 134R
      protein of Yaba-like disease virus (Y134R) indicated that it is similar to
      cellular proteins of the IL-10 family, specifically IL-19, IL-20 and IL-24. A
      flag-tagged Y134R was expressed from mammalian cells and identified as a
      secreted, monomeric glycoprotein that stimulated signal transduction from class
      II cytokine receptors IL-20Ralpha/IL-20Rbeta (IL-20R type1) and IL-22R/IL-20Rbeta
      (IL-20R type 2). Y134R induced phosphorylation of signal transducers and
      activators of transcription, their translocation to the nucleus and the induction
      of reporter gene expression. In contrast, Y134R was unable to induce similar
      responses from either the IL-22 or IFN-lambda (IL-28A, IL-28B, IL-29) class II
      cytokine receptors. To examine the role Y134R plays during a poxvirus infection,
      a vaccinia virus recombinant expressing Y134R was constructed and tested in a
      murine intranasal infection model. Compared with control viruses, the virus
      expressing Y134R had a reduced virulence, manifested by reduced weight loss,
      signs of illness and virus titres in infected organs. These results demonstrate
      that Y134R is a new viral member of the IL-10-related cytokine family and that
      its activity in vivo affects virus virulence.

PMID- 15166423
TI  - Recent isolates of parapoxvirus of Finnish reindeer (Rangifer tarandus tarandus)
      are closely related to bovine pseudocowpox virus.
AB  - Cases of papular stomatitis in Finnish reindeer have been reported for many
      years. The causative agent was thought to be Orf virus (ORFV), one of the
      Parapoxviridae, although this assumption was based mainly on clinical symptoms,
      pathology and electron microscopy. Here sequence analyses of the viral DNA
      isolated from a recent outbreak of disease in 1999-2000 are presented in
      comparison to that isolated from earlier outbreaks in 1992-1994. The results show
      that the virus isolated from the 1999-2000 outbreak is most closely related to
      Pseudocowpox virus, whereas those from previous years grouped with ORFV. The
      present study describes a method for genetic characterization and classification
      of parapoxviruses (PPVs) and provides for the first time an extended phylogenetic
      analysis of PPVs isolated from Finland, established members of the genus
      Parapoxvirus and selected members of the subfamily Chordopoxvirinae.

PMID- 15166424
TI  - Ubiquitination and proteasome degradation of the E6 proteins of human
      papillomavirus types 11 and 18.
AB  - Human papillomaviruses (HPVs) are aetiological agents for genital warts and
      cervical cancer, the different pathologies of which are dependent on the type of
      HPV infection. Oncogenic HPV types associated with cancer are carcinogens by
      virtue of their oncogene products, which target key regulators of cell
      proliferation and apoptosis. The viral E6 protein from oncogenic HPV types plays
      a central role in carcinogenesis by exploiting the cellular proteasome
      degradation pathway in order to mediate the degradation of cellular proteins,
      most notably the prototype tumour suppressor protein p53. Much less is known
      about the cellular targets of E6 from the non-oncogenic HPV types associated with
      genital warts. It is also unclear what factors influence the level and stability
      of the viral E6 proteins in cells. This report demonstrates that both oncogenic
      and non-oncogenic HPV E6 proteins (from types 18 and 11, respectively) are
      ubiquitinated and targeted for degradation by the 26S proteasome. E6 domains
      required for the induction of p53 or DLG degradation, or E6AP binding, are not
      involved in proteasome-mediated degradation of HPV-18 E6. These results provide
      insight into the cellular modulation of E6 protein levels from both high-risk and
      low-risk HPV types.

PMID- 15166425
TI  - Identification of membrane proteins differentially expressed in human
      papillomavirus type 16 E5-transfected human keratinocytes by nanoelectrospray
      ionization mass spectrometry.
AB  - Membrane proteins differentially expressed in human papillomavirus type 16 (HPV
      16) E5-transfected HaCaT cells have been identified. Membrane proteins were
      isolated and separated by two-dimensional gel electrophoresis. Spots showing
      quantitative differences between E5-transfected and control cells were extracted
      and the proteins were identified by nanoelectrospray ionization mass
      spectrometry. A total of 24 spots was analysed. Among the proteins showing
      differential expression, a decreased amount of calnexin and increased expression
      of hsp70, proteins both involved in maturation and transport of MHC class I
      complexes to the plasma membrane, were noticed. These findings correlate with the
      decreased surface expression of MHC class I molecules described in E5-expressing
      cells, HPV-positive cervical lesions and cervical carcinomas. These results
      stress the value of the proteomic approach, as used here in the experimental
      design, which allows the correlation of changes in host gene expression with
      biological functions of viral genes.

PMID- 15166426
TI  - Enhanced oncogenicity of Asian-American human papillomavirus 16 is associated
      with impaired E2 repression of E6/E7 oncogene transcription.
AB  - Asian-American (AA) variants of human papillomavirus 16 (HPV-16) are linked to a
      high incidence of cervical cancer in Mexico, with some evidence strongly
      suggesting that they are more oncogenic than European (E) variants, including
      their association with younger women and their higher associated risk of cervical
      cancer. Differences in the regulation of viral E6/E7 oncogene transcription by
      the E2 protein may be involved in the higher oncogenicity of AA variants. In E
      variants, E6/E7 oncogene transcription is repressed by the E2 protein and is
      frequently up-regulated by the destruction of the E2 gene during viral
      integration. In contrast, the E2 gene is retained in full in most AA-positive
      carcinomas, raising the possibility of alternative mechanisms for increasing
      viral oncogene transcription. The authors investigated whether the higher
      oncogenicity of AA variants is linked to differences in E6/E7 oncogene
      transcription and the mechanism of E2 deactivation. E6/E7 and E1/E2 transcripts
      were explored by RT-PCR in 53 HPV-16-positive cervical carcinomas, 39 retaining
      (20 European and 19 AA) and 14 having lost (12 European and 2 AA) the E1/E2
      genes, and transcription repression activity of the AA E2 genes was tested in
      four cell lines that constitutively express the beta-galactosidase reporter or
      E6/E7 genes driven by the viral long control region. E6/E7 oncogene transcripts
      were found in all carcinomas, but only those positive for AA variants with E1/E2
      genes had complete E2 transcripts. E2 transcripts were down-regulated by splicing
      in E-positive carcinomas retaining E1/E2. AA E2 genes were impaired for
      repression of E6/E7 oncogene transcription in vivo. These results suggest that
      E6/E7 oncogene expression starts earlier in AA than E variant infections, since E
      variants need E2 to be destroyed or down-regulated.

PMID- 15166427
TI  - TT virus-derived apoptosis-inducing protein induces apoptosis preferentially in
      hepatocellular carcinoma-derived cells.
AB  - TT virus (TTV) is widespread among the global population. Its pathogenic nature
      is still unclear but TTV seems to be more prevalent in cases of hepatitis than in
      healthy individuals. TTV harbours similarities to chicken anaemia virus (CAV).
      Here, the apoptotic potential of a putative TTV-derived 105 aa protein and of the
      main apoptosis-inducing agent of CAV, Apoptin, is compared. As the putative
      protein induced apoptosis in various human hepatocellular carcinoma (HCC) cell
      lines, it was named TTV-derived apoptosis-inducing protein (TAIP). The apoptotic
      activity of TAIP in HCC lines was comparable with that of Apoptin. Conversely,
      unlike Apoptin, TAIP induced only low-level apoptosis in several non-HCC human
      cancer cell lines. The data suggest that TAIP acts in a different way to Apoptin
      as it is selective to a certain degree for HCC lines. This activity of TAIP,
      coupled with the heterogeneity of TTV isolates, may help to explain the variable
      reports of TTV pathogenicity.

PMID- 15166428
TI  - Nef from a primary isolate of human immunodeficiency virus type 1 lacking the
      EE(155) region shows decreased ability to down-regulate CD4.
AB  - The human immunodeficiency virus (HIV) nef gene encodes a 27 kDa myristoylated
      cytosolic protein that has an important role in the pathogenesis of AIDS. One
      function of Nef is the down-regulation of CD4 and MHC class I surface molecules
      in HIV-infected cells. Nef directly isolated from an infected individual (KS2),
      who could be defined as a long-term non-progressor, was compared with Nef from a
      standard laboratory strain, HIV-1 NL4-3. KS2 Nef protein was characterized by its
      lowered ability to down-regulate CD4, while still maintaining the ability to down
      regulate MHC class I. The ability of KS2 Nef to down-regulate CD4 was more
      prominent when CD4 was measured 2-3 days after transfer of the nef gene to the
      target cells, and also when the effect was measured in CD4(+)-enriched primary T
      cells. The amino acid sequence analysis indicated that the most notable feature
      of KS2 Nef was lack of the two glutamic acids: the EE(155) region. When the
      EE(155) region was added to KS2 Nef, the CD4 down-regulation ability was
      increased almost to the level of NL4-3 Nef. Conversely, when the EE(155) region
      was deleted from NL4-3, its CD4 down-regulation ability was dramatically
      impaired. These data suggested that the EE(155) region plays an important role(s)
      in the down-regulation of CD4 by Nef protein and also that primary nef sequences
      could be very useful in identifying the original biological functions of Nef in
      vivo.

PMID- 15166429
TI  - Multiple human immunodeficiency virus type 1 Nef functions contribute to
      efficient replication in primary human macrophages.
AB  - The human immunodeficiency virus type 1 (HIV-1) Nef protein has been shown to
      accelerate viral growth kinetics in primary human T-lymphocytes and macrophages;
      however, the specific function(s) of Nef responsible for this phenotype in
      macrophages is unknown. To address this issue, mutants of a molecularly cloned
      macrophage-tropic isolate, HIV-1(SF162), were generated expressing single point
      mutations that abrogate the ability of Nef to interact with cellular kinases or
      mediate CD4 down-regulation. Infection of primary monocyte-derived macrophages
      (MDM) with these mutant viruses revealed that residues in the PXXP motif
      contribute to efficient replication. Interestingly, viruses expressing alleles of
      Nef defective in CD4 down-modulation activity retain wild-type levels of
      infectivity in single-round assays but exhibited delayed replication kinetics and
      grew to lower titres compared to the wild-type virus in MDM. These data suggest
      that efficient HIV-1 replication is dependent on the ability of Nef to interact
      with cellular kinases and remove CD4 from the surface of infected macrophages.

PMID- 15166430
TI  - CXCR4-mediated T cell apoptosis in human immunodeficiency virus infection.
AB  - Mechanisms of CXCR4-mediated T lymphocyte apoptosis in human immunodeficiency
      virus (HIV) infection are poorly understood. The authors used peripheral blood
      mononuclear cells isolated from HIV type 1-infected subjects and assessed both
      CD4(+) and CD8(+) T cell apoptosis in the presence and absence of CXCR4 blockade
      by AMD3100. Both CD4(+) and CD8(+) T cell apoptosis could be inhibited by CXCR4
      blockade, mostly in acquired immunodeficiency syndrome subjects and more weakly
      in asymptomatic HIV-positive subjects, and depended only partially on the
      syncytium-inducing/non-syncytium-inducing viral envelope phenotype. Immune
      activation of CD8(+), but not CD4(+), T cells was CXCR4-dependent, resulting in
      increased T cell apoptosis. In the presence of monocyte-derived macrophages,
      CXCR4-mediated apoptosis targeted mostly CD8(+) T cells, with CD4(+) T cells
      being more weakly affected. Several immune and viral factors thus play a role in
      CXCR4-mediated T cell apoptosis in HIV infection: CD4/CD8 phenotype, viral
      envelope phenotype, T cell activation and T cell-macrophage intercellular
      contacts.

PMID- 15166432
TI  - Unusually long target site duplications flanking some of the long terminal
      repeats of human endogenous retrovirus K in the human genome.
AB  - Human endogenous retroviruses (HERVs) make up a substantial part of the human
      genome. HERVs and solitary long terminal repeats (solo LTRs) are usually flanked
      by 4-6 nt short direct repeats through the well-known mechanism of their
      integration. A number of solo LTRs flanked by unusually long direct repeats were
      detected in the human genome. These unusual structures might be a product of an
      alternative virus insertion mechanism.

PMID- 15166431
TI  - Development of a homology model for clade A human immunodeficiency virus type 1
      gp120 to localize temporal substitutions arising in recently infected women.
AB  - The virus population transmitted by a human immunodeficiency virus type 1 (HIV-1)
      infected individual undergoes restriction and subsequent diversification in the
      new host. However, in contrast to men, who have limited virus diversity at
      seroconversion, there is measurable diversity in viral envelope gene sequences in
      women infected with clade A HIV-1. In this study, virus sequence diversity in
      three unrelated, clade A infected women preceding and shortly after
      seroconversion was evaluated. It was demonstrated that there is measurable
      evolution of envelope gene sequences over this time interval. Furthermore, in
      each of the three individuals, amino acid substitutions arose at five or six
      positions in sequences derived at or shortly after seroconversion relative to
      sequences obtained from the seronegative sample. Presented here is a model of
      clade A gp120 to determine the location of substitutions that appeared as the
      virus population became established in three clade A HIV-1 infected women.

PMID- 15166433
TI  - Characterization of a mobilization-competent simian immunodeficiency virus (SIV)
      vector containing a ribozyme against SIV polymerase.
AB  - Exploitation of the intracellular virus machinery within infected cells to drive
      an anti-viral gene therapy vector may prove to be a feasible alternative to
      reducing viral loads or overall virus infectivity while propagating the spread of
      a therapeutic vector. Using a simian immunodeficiency virus (SIV)-based system,
      it was shown that the pre-existing retroviral biological machinery within SIV
      infected cells can drive the expression of an anti-SIV pol ribozyme and mobilize
      the vector to transduce neighbouring cells. The anti-SIV pol ribozyme vector was
      derived from the SIV backbone and contained the 5'- and 3'LTR including
      transactivation-response, Psi and Rev-responsive elements, thus requiring Tat and
      Rev and therefore limiting expression to SIV-infected cells. The data presented
      here show an early reduction in SIV p27 levels in the presence of the anti-SIV
      pol ribozyme, as well as successful mobilization (vector RNA constituted
      approximately 17 % of the total virus pool) and spread of the vector containing
      this ribozyme. These findings provide direct evidence that mobilization of an
      anti-retroviral SIV gene therapy vector is feasible in the SIV/macaque model.

PMID- 15166435
TI  - Steatosis and intrahepatic lymphocyte recruitment in hepatitis C virus transgenic
      mice.
AB  - To assess the effects of constitutive hepatitis C virus (HCV) gene expression on
      liver, transgenic mice carrying the entire HCV open reading frame inserted in the
      alpha1 antitrypsin (A1AT) gene were generated. Expression of A1AT/HCV mRNA was
      found to be mainly limited to perivascular areas of the liver as indicated by in
      situ hybridization analysis. HCV core protein was detected in Western blots of
      liver extracts, whereas the expression of E2, NS3 and NS5 proteins was revealed
      by immunostaining of liver samples using HCV-specific antisera. Histological
      analysis of HCV transgenic mice showed that these animals develop extensive
      steatosis, but very little necrosis of liver tissue. Moreover, a consistent T
      cell infiltrate and a slight hepatocyte proliferation were observed. Phenotypic
      analysis of cells infiltrating the liver indicated that recruitment and/or
      expansion of residing CD8(+), NK, NKT and gammadelta T cells occurred in
      transgenic animals. Among these cells, a large fraction of CD8(+) T lymphocytes
      released mainly IL-10 and, to a lesser extent, IFN-gamma upon mitogenic
      stimulation in vitro. Furthermore, both intrahepatic lymphocytes and splenocytes
      did not produce cytokines in response to HCV antigens. Thus, these data indicate
      that constitutive expression of HCV proteins may be responsible for intrahepatic
      lymphocyte recruitment in absence of viral antigen recognition. This response is
      likely to be driven by virus-induced cellular factors and may play a significant
      role in the immunopathology of chronic HCV infection and liver disease.

PMID- 15166434
TI  - Characterization of the genome and structural proteins of hepatitis C virus
      resolved from infected human liver.
AB  - In the absence of satisfactory cell culture systems for hepatitis C virus (HCV),
      virtually all that is known about the proteins of the virus has been learned by
      the study of recombinant proteins. Characterization of virus proteins from
      patients with HCV has been retarded by the low virus titre in blood and limited
      availability of infected tissue. Here, the authors have identified a primary
      infection in a liver transplanted into an immunodeficient patient with chronic
      HCV. The patient required re-transplant and the infected liver, removed 6 weeks
      after the initial transplant, had a very high titre of HCV, 5 x 10(9)
      International Units (IU) per gram of liver. The density distribution of HCV in
      iodixanol gradients showed a peak at 1.04 g x ml(-1) with 73 % of virus below
      1.08 g x ml(-1). Full-length HCV RNA was detected by Northern blotting and the
      ratio between positive- and negative-strand HCV RNA was determined as 60. HCV was
      partially purified by precipitation with heparin/Mn(2+) and a single species of
      each of the three structural proteins, core, E1 and E2, was detected by Western
      blotting. The molecular mass of core was 20 kDa, which corresponds to the mature
      form from recombinant sources. The molecular mass of glycoprotein E1 was 31 kDa
      before and 21 kDa after deglycosylation with PNGase F or endoglycosidase H.
      Glycoprotein E2 was 62 kDa before and 36 kDa after deglycosylation, but E2-P7 was
      not detected. This was in contrast to recombinant sources of E2 which contain E2
      P7.

PMID- 15166436
TI  - Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte
      epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402
      binding motifs.
AB  - The human leukocyte antigen (HLA)-A*2402 is common in Asians. The authors
      attempted to identify epitopes for HLA-A*2402-restricted, hepatitis C virus (HCV)
      specific CD8(+) T cells by an enzyme-linked immunospot (ELISpot) assay using
      peripheral blood CD8(+) T cells from HLA-A*2402-positive hepatitis C patients and
      synthetic HCV peptides based on HLA-A*2402-binding motifs and the amino acid
      sequence of type 1b HCV. Ten novel epitopes were identified in five of seven HLA
      A*2402-positive patients with acute or short-term chronic HCV infection (<3
      years), but in none of four with longer-term chronic infection (>10 years). Only
      one of the ten epitopes proved to be definitely HLA-A*2402-restricted. Another
      epitope was identified in one of two HLA-A*2402-negative acute hepatitis C
      patients. In two of the six patients with positive CD8(+) T cell responses, the
      targeted epitopes were multiple. The same epitope was targeted in two patients.
      When patients with unresolved acute HCV infection were treated with alpha
      interferon, peripheral blood HCV-specific CD8(+) T cells decreased with
      resolution of the hepatitis. In conclusion, CD8(+) T cell responses to HCV
      infection are heterogeneous. One definite HLA-A*2402-restricted and ten probably
      non-HLA-A*2402-restricted epitopes were identified. Patients with short-term HCV
      infection are suitable for searching for novel HCV epitopes, but peripheral blood
      HCV-specific CD8(+) T cells decrease markedly after loss of antigenic
      stimulation.

PMID- 15166437
TI  - Priming with CpG-enriched plasmid and boosting with protein formulated with CpG
      oligodeoxynucleotides and Quil A induces strong cellular and humoral immune
      responses to hepatitis C virus NS3.
AB  - Cell-mediated immune responses to hepatitis C virus (HCV) proteins play a key
      role in recovery from infection. The NS3 protein of HCV is of special interest,
      since it is one of the most conserved proteins and NS3-specific immune responses
      are stronger and more frequently observed in patients resolving the infection
      than in chronically infected patients. Since these characteristics make NS3 an
      attractive vaccine candidate, the objective of this study was to optimize NS3
      specific immune responses. Results from this group first demonstrated that a
      plasmid enriched with 24 CpG motifs (pBISIA24-NS3) tends to induce the strongest
      and most consistent Th1-biased immune response. Subsequently, it was shown that
      NS3 formulated with CpG oligodeoxynucleotide and Quil A (rNS3+CpG+Quil A)
      adjuvants induces a balanced immune response in mice, whereas rNS3 combined with
      either CpG or Quil A elicits a Th2-biased response. To further enhance NS3
      specific cell-mediated immune responses, a vaccination regime consisting of
      priming with pBISIA24-NS3, followed by boosting with rNS3+CpG+Quil A, was
      explored in mice and pigs. When compared to immunization with rNS3+CpG+Quil A,
      this regime shifted the immune response to a Th1-type response and, accordingly,
      enhanced MHC I-restricted killing by cytotoxic T lymphocytes in mice. Although
      immunization with pBISIA24-NS3 also induced a Th1-biased response, including
      cytotoxicity in the mice, the humoral response was significantly lower than that
      induced by the DNA prime-protein boost regime. These results demonstrate the
      advantage of a DNA prime-protein boost approach in inducing a strong NS3-specific
      cell-mediated, as well as humoral, immune response, in both inbred laboratory and
      outbred large animal species.

PMID- 15166438
TI  - Enhanced hepatitis C virus NS3 specific Th1 immune responses induced by co
      delivery of protein antigen and CpG with cationic liposomes.
AB  - Mice were immunized intramuscularly with free recombinant hepatitis C virus (HCV)
      NS3 (non-structural protein 3) protein, liposomes encapsulating rNS3 or rNS3 and
      CpG mixture, liposomes co-encapsulating rNS3 and CpG or liposomes co
      encapsulating rNS3 and GpC. Liposomes co-encapsulating rNS3 and CpG induced a
      much higher titre of anti-HCV NS3 IgG and the dominant IgG subtype was IgG2a.
      Liposomes co-encapsulating rNS3 and GpC also induced high levels of anti-HCV NS3
      IgG antibody, but the dominant IgG subtype was still IgG1, the same as in free
      HCV/NS3 immunized mice. Liposomes encapsulating rHCV NS3 and the mixture of rHCV
      NS3 and CpG did not increase the antibody response but switched the IgG subtype.
      A cytokine profile analysis revealed that the levels of Th1 cytokines in the mice
      immunized with liposomes co-encapsulating rHCV NS3 and CpG were significantly
      higher than in other mice while the levels of Th2 cytokine were significantly
      lower than in the mice immunized with naked rNS3. IL-12 in the mice immunized
      with liposome-NS3-CpG was significantly higher than in other mice. In conclusion,
      liposomes co-encapsulating HCV NS3 and CpG are a good candidate vaccine to induce
      strong Th1 immune responses against hepatitis C viruses.

PMID- 15166439
TI  - Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B.
AB  - Coxsackievirus B (CVB) is often associated with aseptic meningitis and
      encephalitis, but the six serotypes of CVB vary in their relative disease
      severity. To elucidate the detailed mechanisms of CVB-induced cytopathological
      effects, the morphological and biochemical characteristics caused by the CVB
      serotypes in mouse primary cortical neuronal cells were investigated. By 24 h
      post-infection, all CVB serotypes except CVB2 induced severe cytotoxic
      alterations, including a loss of neurites. Both fluorescence and transmission
      electron microscopy revealed CVB-induced morphological changes indicative of
      apoptosis, including heavily condensed nuclei, subsequent chromatin condensation
      into the periphery of the nuclei and oligonucleosomal DNA fragmentation. It was
      also found that infection with all six CVB serotypes led to productive virus
      replication, which was completed prior to an apoptotic signal. The caspase
      inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone significantly
      inhibited nuclear changes associated with virus-induced apoptosis, but had less
      effect on virus-associated cytopathic effects and no effect on virus production.
      In contrast, the transcription inhibitor actinomycin D profoundly inhibited all
      three virus-induced events. Taken together, these findings demonstrate that all
      six CVB serotypes can efficiently replicate in mouse cortical neuronal cells and
      that productive replication of these CVBs, except for CVB2, induces multiple
      cytopathological effects, including apoptotic alterations.

PMID- 15166440
TI  - The Rhopalosiphum padi virus 5' internal ribosome entry site is functional in
      Spodoptera frugiperda 21 cells and in their cell-free lysates: implications for
      the baculovirus expression system.
AB  - Cap-independent internal initiation of translation occurs on a number of viral
      and cellular mRNAs and is directed by internal ribosome entry site (IRES)
      elements. Rhopalosiphum padi virus (RhPV) is a member of the Dicistroviridae.
      These viruses have single-stranded, positive-sense RNA genomes that contain two
      open reading frames, both preceded by IRES elements. Previously, the activity of
      the RhPV 5' UTR IRES has been demonstrated in mammalian, Drosophila and wheat
      germ in vitro translation systems. It is now shown that this IRES also functions
      within Spodoptera frugiperda (Sf21) cells which are widely used in the
      baculovirus expression system, and in a novel Sf21 cell-based lysate system.
      Inclusion of the RhPV IRES in a dicistronic reporter mRNA transcript increased
      translation of the second cistron 23-fold within Sf21 cells. In contrast, the
      encephalomyocarditis virus IRES was inactive in both systems. The RhPV IRES
      therefore has the potential to be utilized in insect cell expression systems.

PMID- 15166441
TI  - Gut-homing (alpha(4)beta(7)(+)) Th1 memory responses after inactivated poliovirus
      immunization in poliovirus orally pre-immunized donors.
AB  - Mucosal infections are prevented by a specialized local immune system. Immune
      cells of this compartment can also be found in the blood and are characterized by
      the expression of mucosa-specific homing molecules. Here, the cellular immune
      responses after inactivated poliovirus immunization (IPV) in poliovirus orally
      pre-immunized donors were investigated. Subcutaneous IPV induced a transient
      increase in the proliferative response against poliovirus antigen and in the
      number of poliovirus-specific CD4(+) T cells in the blood of the vaccinees. These
      cells were characterized to be of the effector memory type (CD45RA(
      )/CD45RO(+)/CCR7(-)/CD27(+)) and expressed the homing molecule alpha(4)beta(7),
      indicating their origin from the gut. Together these data show the recurrence of
      gut-derived poliovirus-specific cells upon IPV and evaluate the whole-blood assay
      as a powerful tool for monitoring the success of a vaccination.

PMID- 15166442
TI  - Poliovirus binding to its receptor in lipid bilayers results in particle
      specific, temperature-sensitive channels.
AB  - Poliovirus (PV) infection starts with binding to its receptor (PVR), followed by
      a receptor-aided, temperature-sensitive conformational change of the infectious
      particle (sedimenting at 160S) to a particle which sediments at 135S. Reported in
      this communication is the successful incorporation into lipid bilayers of two
      forms of the receptor: the full-length human receptor and a modified clone in
      which the extracellular domains of the receptor were fused to a
      glycosylphosphatidylinositol tail. Addition of virus (160S) to receptor
      containing bilayers leads to channel formation, whereas no channels were observed
      when the receptor-modified viral particle (135S) was added. Increasing the
      temperature from 21 to 31 degrees C led to a 10-fold increase in the magnitude of
      the single channel conductance, which can be interpreted as a conformational
      change in the channel structure. A mutant PV with an amino acid change in VP4
      (one of the coat proteins) which is defective in genome uncoating failed to
      produce channels, suggesting that VP4 might be involved in the channel
      architecture. These studies provide the first electrophysiological
      characterization of the interactions between poliovirus and its receptor
      incorporated into a lipid bilayer membrane. Furthermore, they form the foundation
      for future studies aiming at defining the molecular architecture of the virus
      receptor complex.

PMID- 15166443
TI  - Phylogenetic analysis of wild-type 1 polioviruses isolated during the final
      period of transmission in Turkey.
AB  - The last poliomyelitis case associated with a wild poliovirus in Turkey occurred
      in November 1998. This was the last known case of paralytic poliomyelitis caused
      by indigenous wild poliovirus in the World Health Organization's European Region.
      This study investigated the genetic relationships of wild-type 1 polioviruses at
      the latest period of transmission. A phylogenetic tree was constructed on the
      basis of the VP1/2A sequence from 14 wild-type 1 polioviruses isolated from
      Turkey in 1994-1998, along with those from other areas of the world. The Turkey
      isolates in the latest period of transmission were closely related to each other,
      forming a cluster distinct from other strains. The results showed that these
      viruses had been spreading indigenously in the eastern and south-eastern parts of
      Turkey, and ceased transmission there during 1998. This finding serves as a
      reference for future poliovirus surveillance both in Turkey and worldwide.

PMID- 15166444
TI  - Complete genome sequences of all members of the species Human enterovirus A.
AB  - The species Human enterovirus A (HEV-A) in the family Picornaviridae consists of
      coxsackieviruses (CV) A2-A8, A10, A12, A14 and A16 and enterovirus 71. Complete
      genome sequences for the prototype strains of the 10 serotypes whose sequences
      were not represented in public databases have been determined and analysed in
      conjunction with previously available complete sequences in GenBank. Members of
      HEV-A are monophyletic relative to all other human enterovirus species in all
      regions of the genome except in the 5' non-translated region (NTR), where they
      are known to cluster with members of HEV-B. The HEV-A prototype strains were
      about 66 to 86 % identical to one another in deduced capsid amino acid sequence.
      Antigenic cross-reactivity has been reported between CVA3-Olson and CVA8-Donovan,
      between CVA5-Swartz and CVA12-Texas-12 and between CVA16-G-10 and EV71-BrCr.
      Similarity plots, individual sequence comparisons and phylogenetic analyses
      demonstrate a high degree of capsid sequence similarity within each of these
      three pairs of prototype strains, providing a molecular basis for the observed
      antigenic relationships. In several cases, phylogenies constructed from the
      structural (P1) and non-structural regions of the genome (P2 and P3) are
      incongruent. The incongruent phylogenies and the similarity plot analyses imply
      that recombination has played a role in the evolution of the HEV-A prototype
      strains. CVA6-Gdula clearly contains sequences that are also present in CVA10
      Kowalik and CVA12-Texas-12, suggesting that these three strains have a shared
      evolutionary history despite their lack of similarity in the capsid region.

PMID- 15166445
TI  - Determination and analysis of the complete genomic sequence of avian hepatitis E
      virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV.
AB  - Avian hepatitis E virus (avian HEV), recently identified from a chicken with
      hepatitis-splenomegaly syndrome in the United States, is genetically and
      antigenically related to human and swine HEVs. In this study, sequencing of the
      genome was completed and an attempt was made to infect rhesus monkeys with avian
      HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp
      in length, which is about 600 bp shorter than that of human and swine HEVs.
      Similar to human and swine HEV genomes, the avian HEV genome consists of a short
      5' non-coding region (NCR) followed by three partially overlapping open reading
      frames (ORFs) and a 3'NCR. Avian HEV shares about 50 % nucleotide sequence
      identity over the complete genome, 48-51 % identity in ORF1, 46-48 % identity in
      ORF2 and only 29-34 % identity in ORF3 with human and swine HEV strains.
      Significant genetic variations such as deletions and insertions, particularly in
      ORF1 of avian HEV, were observed. However, motifs in the putative functional
      domains of ORF1, such as the helicase and methyltransferase, were relatively
      conserved between avian HEV and mammalian HEVs, supporting the conclusion that
      avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that
      avian HEV represents a branch distinct from human and swine HEVs. Swine HEV
      infects non-human primates and possibly humans and thus may be zoonotic. An
      attempt was made to determine whether avian HEV also infects across species by
      experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus
      infection was not observed in the inoculated monkeys as there was no
      seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation.
      The results from this study confirmed that avian HEV is related to, but distinct
      from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not
      transmissible to non-human primates.

PMID- 15166446
TI  - Molecular determinants of antigenicity of two subtypes of the tick-borne
      flavivirus Omsk haemorrhagic fever virus.
AB  - In 1964, D. H. Clarke defined two antigenic subtypes of Omsk haemorrhagic fever
      virus (OHFV) based on polyclonal antibody absorption and haemagglutination
      assays. The current report defines the molecular basis for these antigenic
      subtypes by comparison of the complete genomes of OHFV strains Kubrin (subtype I)
      and Bogoluvovska (subtype II). There were six nucleotide differences between
      these two strains throughout the entire genome and they encoded four amino acid
      changes including three in the viral envelope (E) protein. Two of these changes
      were in solvent-exposed regions of domain 3 of the E protein, one of which lies
      in a region that could easily function in virus-host cell or virus-antibody
      interactions. These results demonstrate the minimal changes that are required to
      significantly alter the antigenicity of flaviviruses and also demonstrate the
      tremendous genetic stability of the tick-borne flaviviruses.

PMID- 15166447
TI  - Shift in Japanese encephalitis virus (JEV) genotype circulating in northern
      Vietnam: implications for frequent introductions of JEV from Southeast Asia to
      East Asia.
AB  - This study analyses the evolutionary relatedness of 16 Japanese encephalitis
      virus (JEV) isolates (nine from Vietnam and seven from Japan) to previously
      published JEV strains using E gene sequence data. Vietnamese and Japanese strains
      isolated between 1986 and 1990 were found to cluster in genotype 3. However, more
      recent Vietnamese and Japanese strains isolated between 1995 and 2002 grouped
      within genotype 1, now a dominant though previously unreported genotype in
      Vietnam. In addition, in this study, strains isolated between 1995 and 2002 were
      more closely related to those isolated in the 1990s than to the older genotype 1
      strains. Recently, the introduction of JEV genotype 1 into Japan and Korea has
      also been reported. Hence this genotype shift phenomenon may be occurring
      throughout all East Asia. Further studies on JEV ecology are needed to clarify
      the mechanism of JEV genotype 1 spread to new territories.

PMID- 15166448
TI  - Interaction of classical swine fever virus with dendritic cells.
AB  - Functional disruption of dendritic cells (DCs) is an important strategy for viral
      pathogens to evade host defences. Monocytotropic viruses such as classical swine
      fever virus (CSFV) could employ such a mechanism, since the virus can suppress
      immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV
      was shown to infect and efficiently replicate in monocyte- and in bone marrow
      derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor
      CD80/86 expression. Stimulation of DCs with IFN-alpha/TNF-alpha or polyinosinic
      polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and
      CD80/86 expression, both with mock-treated and infected DCs. In addition, the T
      cell stimulatory capacity of CSFV-infected DCs was maintained both in a
      polyclonal T cell stimulation and in specific antigen-presentation assays,
      requiring antigen uptake and processing. Interestingly, similar to macrophages,
      CSFV did not induce IFN-alpha responses in these DCs and even suppressed pIC
      induced IFN-alpha induction. Other cytokines including interleukin (IL)-6, IL-10,
      IL-12 and TNF-alpha were not modulated. Taken together, these results
      demonstrated that CSFV can replicate in DCs and control IFN type I responses,
      without interfering with the immune reactivity. These results are interesting
      considering that DC infection with RNA viruses usually results in DC activation.

PMID- 15166449
TI  - Biochemical characterization of the respiratory syncytial virus P-P and P-N
      protein complexes and localization of the P protein oligomerization domain.
AB  - The RNA-dependent RNA polymerase complex of respiratory syncytial virus (RSV) is
      composed of the large polymerase (L), the phosphoprotein (P), the nucleocapsid
      protein (N) and the co-factors M2-1 and M2-2. The P protein plays a central role
      within the replicase-transcriptase machinery, forming homo-oligomers and
      complexes with N and L. In order to study P-P and N-P complexes, and the role of
      P phosphorylation in these interactions, the human RSV P and N proteins were
      expressed in E. coli as His-tagged or GST-fusion proteins. The non-phosphorylated
      status of recombinant P protein was established by mass spectrometry. GST-P and
      GST-N fusion proteins were able to interact with RSV proteins extracted from
      infected cells in a GST pull-down assay. When co-expressed in bacteria, GST-P and
      His-P were co-purified by glutathione-Sepharose affinity, showing that the RSV P
      protein can form oligomers within bacteria. This result was confirmed by chemical
      cross-linking experiments and gel filtration studies. The P oligomerization
      domain was investigated by a GST pull-down assay using a series of P deletion
      constructs. This domain was mapped to a small region situated in the central part
      of P (aa 120-150), which localized in a computer-predicted coiled-coil domain.
      When co-expressed in bacteria, RSV N and P proteins formed a soluble complex that
      prevented non-specific binding of N to bacterial RNA. Therefore, RSV P protein
      phosphorylation is not required for the formation of P-P and N-P complexes, and P
      controls the RNA binding activity of N.

PMID- 15166450
TI  - Identification of small-animal and primate models for evaluation of vaccine
      candidates for human metapneumovirus (hMPV) and implications for hMPV vaccine
      design.
AB  - Human metapneumovirus (hMPV), a recently identified paramyxovirus, is the
      causative agent of respiratory tract disease in young children. Epidemiological
      studies have established the presence of hMPV in retrospective as well as current
      clinical samples in Europe, USA, Canada, Hong Kong and Australia. The hMPV
      disease incidence rate varied from 7 to 12 %. This rate of disease attack places
      hMPV in severity between respiratory syncytial virus and human parainfluenza
      virus type 3, two common respiratory pathogens of young children, the elderly and
      immunosuppressed individuals. To evaluate the effectiveness and safety of future
      hMPV antiviral drugs, therapeutic and prophylactic monoclonal antibodies (mAbs),
      and vaccine candidates, it was necessary to identify small-animal and primate
      models that efficiently supported hMPV replication in the respiratory tract and
      produced neutralizing serum antibodies, commonly a clinical correlate of
      protection in humans. In this study, various rodents (mice, cotton rats, hamsters
      and ferrets) and two primate species, rhesus macaques and African green monkeys
      (AGMs), were evaluated for hMPV replication in the respiratory tract. The results
      showed that hamsters, ferrets and AGMs supported hMPV replication efficiently and
      produced high levels of hMPV-neutralizing antibody titres. Hamsters vaccinated
      with subgroup A hMPV were protected from challenge with subgroup A or subgroup B
      hMPV, which has implications for hMPV vaccine design. Although these animal
      models do not mimic human hMPV disease signs, they will nevertheless be
      invaluable for the future evaluation of hMPV antivirals, mAbs and vaccines.

PMID- 15166451
TI  - Cell surface activation of the alternative complement pathway by the fusion
      protein of measles virus.
AB  - Measles virus (MV)-infected cells are activators of the alternative human
      complement pathway, resulting in high deposition of C3b on the cell surface.
      Activation was observed independent of whether CD46 was used as a cellular
      receptor and did not correlate with CD46 down-regulation. The virus itself was an
      activator of the alternative pathway and was covered by C3b/C3bi, resulting in
      some loss in infectivity without loss of virus binding to target cells. The cell
      surface expression of MV fusion (F), but not haemagglutinin, envelope protein
      resulted in complement activation of the Factor B-dependent alternative pathway
      in a dose-dependent manner and F-C3b complexes were formed. The underlying
      activation mechanism was not related to any decrease in cell surface expression
      of the complement regulators CD46 and CD55. The C3b/C3bi coating of MV-infected
      cells and virus should ensure enhanced targeting of MV antigens to the immune
      system, through binding to complement receptors.

PMID- 15166452
TI  - Mapping of domains responsible for nucleocapsid protein-phosphoprotein
      interaction of Henipaviruses.
AB  - Hendra virus (HeV) and Nipah virus (NiV) are members of a new genus, Henipavirus,
      in the family paramyxoviridae. Each virus encodes a phosphoprotein (P) that is
      significantly larger than its counterparts in other known paramyxoviruses. The
      interaction of this unusually large P with its nucleocapsid protein (N) was
      investigated in this study by using recombinant full-length and truncated
      proteins expressed in bacteria and a modified protein-blotting protein-overlay
      assay. Results from our group demonstrated that the N and P of both viruses were
      able to form not only homologous, but also heterologous, N-P complexes, i.e. HeV
      N was able to interact with NiV P and vice versa. Deletion analysis of the N and
      P revealed that there were at least two independent N-binding sites on P and they
      resided at the N and C termini, respectively. Similarly, more than one P-binding
      site was present on N and one of these was mapped to a 29 amino acid (aa) C
      terminal region, which on its own was sufficient to interact with the extreme C
      terminal 165 aa region of P.

PMID- 15166453
TI  - Ser-123 of the large antigen of hepatitis delta virus modulates its cellular
      localization to the nucleolus, SC-35 speckles or the cytoplasm.
AB  - Hepatitis delta virus (HDV) is a defective virus and requires hepatitis B virus
      (HBV) to supply envelope proteins (HBsAg) for maturation and secretion. It is
      known that two proteins produced by HDV, the small (SDAg) and large (LDAg)
      antigens, are located in the nucleolus, speckles and the cytoplasm and are
      involved in genome replication and virion packaging. However, little is known
      about how they are targeted to the specific sites where they act. A green
      fluorescence protein fused to LDAg (GFP-LD) has been shown previously to
      translocate from the nucleolus to SC-35 speckles in the presence of the casein
      kinase II inhibitor dichlororibofuranosyl benzimidazole. In this study, we
      determined which amino acids of GFP-LD were responsible for the translocation
      from the nucleolus to SC-35 speckles and created three GFP-LD derivatives, GFP
      LDS2A, GFP-LDS123A and GFP-LDS2/123A. Fluorescence microscopy studies showed that
      Ser-123 mutants had a high tendency to target SC-35 speckles in both transfected
      HeLa and HuH-7 cells and suggested that Ser-123, but not Ser-2, plays a role in
      modulating LDAg translocation to the nucleolus or to SC-35 speckles. This study
      also demonstrated that HBsAg plays a role in facilitating the transportation of
      LDAg from the nucleus to cytoplasm. Compared with GFP-LD and GFP-LDS2A, mutants
      of Ser-123 were less efficiently transported to the cytoplasm and resulted in a
      lower level of secretion. In contrast, little or no isoprenylation mutant was
      observed in the cytoplasm of HuH-7 cells expressing HbsAg, suggesting that the
      isoprenylation of LDAg plays a role in export from the nucleus. Thus, the current
      study demonstrated that both cis and trans elements modulate HDAg translocation
      to various subcellular sites.

PMID- 15166454
TI  - During entry of alphaviruses, the E1 glycoprotein molecules probably form two
      separate populations that generate either a fusion pore or ion-permeable pores.
AB  - Studies using the alphavirus Semliki Forest virus have indicated that the viral
      E1 fusion protein forms two types of pore: fusion pores and ion-permeable pores.
      The formation of ion-permeable pores has not been generally accepted, partly
      because it was not evident how the protein might form these different pores. Here
      it is proposed that the choice of the target membrane determines whether a fusion
      pore or ion-permeable pores are formed. The fusion protein is activated in the
      endosome and for steric reasons only a fraction of the activated molecules can
      interact with the endosomal membrane. This target membrane reaction forms the
      fusion pore. It is proposed that the rest of the activated molecules interact
      with the membrane in which the protein is anchored and that this self-membrane
      reaction leads to formation of ion-permeable pores, which can be detected in the
      target membrane after fusion of the viral membrane into the target membrane.

PMID- 15166455
TI  - Cytokine production by virus-specific CD8(+) T cells varies with activation state
      and localization, but not with TCR avidity.
AB  - The ability of virus-specific CD8(+) T cells to produce cytokines was studied in
      mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis
      virus. Intracellular staining was used to visualize cytokine-producing CD8(+) and
      CD4(+) T cells. Overall, virus-specific CD8(+) T cells produce a similar range of
      cytokines (IFN-gamma, TNF-alpha, IL-2, GM-CSF, RANTES, MIP-1alpha and MIP-1beta)
      as CD4(+) T cells, but the relative distribution of cytokine-producing subsets is
      different. Moreover, cytokine-producing CD8(+) T cells were found to dominate
      numerically at all time-points tested. Co-staining for more than one cytokine
      revealed that while all cytokine-producing CD8(+) T cells synthesized IFN-gamma,
      additional cytokines were produced by partly overlapping subsets of this
      population. The frequency of cells producing more than one cytokine was higher in
      a tertiary site (peritoneum) and generally increased with transition into the
      memory phase; however, GM-CSF producing cells were only present transiently.
      Concerning factors predicted to influence the distribution of cytokine-producing
      subsets, IFN-gamma and IL-12 did not play a role, nor was extensive virus
      replication essential. Notably, regarding the heterogeneity in cytokine
      production by individual cells with similar epitope specificity, variation in TCR
      avidity was not the cause, since in vivo-activated TCR transgene-expressing cells
      were as heterogeneous in cytokine expression as polyclonal cells specific for the
      same epitope.

PMID- 15166456
TI  - Evidence of rotavirus intragenic recombination between two sublineages of the
      same genotype.
AB  - Rotavirus G4 prevalence increased during the past decade, with one of the highest
      prevalences reported during rotavirus surveillance in Argentina. Intragenotype
      diversity analysis has led to its subdivision into lineages (I and II) and
      sublineages (Ia-Id). On analysis of Argentine and G4 VP7 sequences from other
      locations, one Argentine strain (ArgRes1723) appeared to be an intermediate
      between G4 sublineages Ib and Ic. Similarity and bootscanning analyses and
      Sawyer's test were carried out to demonstrate the recombinant nature of this
      strain. It was concluded that intragenic recombination occurred between sequences
      of sublineages Ib and Ic, with a crossover point between nucleotide positions 336
      and 387. This study constitutes the first report of a mechanism of evolution in
      rotaviruses that is currently considered unusual - a recombination event between
      two strains of the same rotavirus genotype. These results will help increase
      current knowledge about rotavirus evolution and divergence, improving our
      understanding of the adaptation mechanisms used by these viruses.

PMID- 15166457
TI  - Rapid identification of coronavirus replicase inhibitors using a selectable
      replicon RNA.
AB  - A previously unknown coronavirus (CoV) is the aetiological agent causing severe
      acute respiratory syndrome (SARS), for which an effective antiviral treatment is
      urgently needed. To enable the rapid and biosafe identification of coronavirus
      replicase inhibitors, we have generated a non-cytopathic, selectable replicon RNA
      (based on human CoV 229E) that can be stably maintained in eukaryotic cells. Most
      importantly, the replicon RNA mediates reporter gene expression as a marker for
      coronavirus replication. We have used a replicon RNA-containing cell line to test
      the inhibitory effect of several compounds that are currently being assessed for
      SARS treatment. Amongst those, interferon-alpha displayed the strongest
      inhibitory activity. Our results demonstrate that coronavirus replicon cell lines
      provide a versatile and safe assay for the identification of coronavirus
      replicase inhibitors. Once this technology is adapted to SARS-CoV replicon RNAs,
      it will allow high throughput screening for SARS-CoV replicase inhibitors without
      the need to grow infectious SARS-CoV.

PMID- 15166458
TI  - Characterization of regulatory elements within the coat protein (CP) coding
      region of Tobacco mosaic virus affecting subgenomic transcription and green
      fluorescent protein expression from the CP subgenomic RNA promoter.
AB  - A replicon based on Tobacco mosaic virus that was engineered to express the open
      reading frame (ORF) of the green fluorescent protein (GFP) gene in place of the
      native coat protein (CP) gene from a minimal CP subgenomic (sg) RNA promoter was
      found to accumulate very low levels of GFP. Regulatory regions within the CP ORF
      were identified that, when presented as untranslated regions flanking the GFP
      ORF, enhanced or inhibited sg transcription and GFP expression. Full GFP
      expression from the CP sgRNA promoter required more than the first 20 nt of the
      CP ORF but not beyond the first 56 nt. Further analysis indicated the presence of
      an enhancer element between nt +25 and +55 with respect to the CP translation
      start site. The inclusion of this enhancer sequence upstream of the GFP ORF led
      to elevated sg transcription and to a 50-fold increase in GFP accumulation in
      comparison with a minimal CP promoter in which the entire CP ORF was displaced by
      the GFP ORF. Inclusion of the 3'-terminal 22 nt had a minor positive effect on
      GFP accumulation, but the addition of extended untranslated sequences from the 3'
      terminus of the CP ORF downstream of the GFP ORF was basically found to inhibit
      sg transcription. Secondary structure analysis programs predicted the CP sgRNA
      promoter to reside within two stable stem-loop structures, which are followed by
      an enhancer region.

PMID- 15166459
TI  - Evidence for contribution of an internal ribosome entry site to intercellular
      transport of a tobamovirus.
AB  - Previously, it has been shown that tobacco mosaic virus (TMV) U1 and crucifer
      infecting TMV contain a 75 nt internal ribosome entry site (IRES) upstream of
      movement protein (MP) gene (IRES(U1)(MP,75) and IRES(CR)(MP,75), respectively). A
      movement-deficient TMV mutant, KK6, has been constructed previously [Lehto, K.,
      Grantham, G. L. & Dawson, W. O. (1990). Virology 174, 145-157] by insertion of
      the second coat protein subgenomic promoter (CP SGP-2) upstream of the MP gene,
      in addition to the natural CP SGP-1. Here, the authors compare the efficiency of
      movement function expression by KK6 and a derivative, K86, obtained by insertion
      of IRES(CR)(MP,75) between the CP SGP-2 and MP genes resulting in restoration of
      IRES(CR)(MP,75) function in the 5'-untranslated sequence of the I(2) subgenomic
      RNA of K86. The data indicate that the efficiency of K86 movement was largely
      restored by this insertion, which was apparently due to the translation-enhancing
      ability of IRES(CR)(MP,75).

PMID- 15166460
TI  - Tomato yellow leaf curl Sardinia virus can overcome transgene-mediated RNA
      silencing of two essential viral genes.
AB  - To evaluate RNA silencing for the control of geminivirus infection, two classes
      of post-transcriptionally silenced (PTS) plants were tested using Tomato yellow
      leaf curl Sardinia virus (TYLCSV) Rep-210-transgenic plants, a sensexantisense
      hybrid and two multicopy sense lines. In both classes, PTS plants accumulated low
      or undetectable amounts of Rep-210 protein and mRNA but high amounts of Rep-210
      small interfering RNAs. PTS plants were susceptible to TYLCSV when challenged by
      agroinoculation or using high viruliferous whitefly (Bemisia tabaci) pressure,
      although some plants were resistant at low whitefly pressure. Delayed infections
      were also observed, indicating that TYLCSV could overcome transgene silencing of
      rep and of the nested C4 gene. TYLCSV infection boosted transgene silencing but
      this did not lead to recovery. The data suggest that if the virus reaches a
      threshold level of expression/replication in the initially infected cells then
      virus spreading can no longer be prevented.

PMID- 15166461
TI  - The C terminus of the movement protein of Brome mosaic virus controls the
      requirement for coat protein in cell-to-cell movement and plays a role in long
      distance movement.
AB  - The 3a movement protein (MP) plays a central role in the movement of Brome mosaic
      virus (BMV). To identify the functional regions in BMV MP, 24 alanine-scanning
      (AS) MP mutants of BMV were constructed. Infectivity of the AS mutants in the
      host plant Chenopodium quinoa showed that the central region of BMV MP is
      important for viral movement and both termini of BMV MP have effects on the
      development of systemic symptoms. A green-fluorescent-protein-expressing RNA3
      based BMV vector containing a 2A sequence from Foot-and-mouth disease virus was
      also constructed. Using this vector, two AS mutants that showed more efficient
      cell-to-cell movement than wild-type BMV were identified. The MPs of these two AS
      mutants, which have mutations at their C termini, mediated cell-to-cell movement
      independently of coat protein (CP), unlike wild-type BMV MP. Furthermore, a BMV
      mutant with a truncation in the C-terminal 42 amino acids of MP was also able to
      move from cell to cell without CP, but did not move systemically, even in the
      presence of CP. These results and an encapsidation analysis suggest that the C
      terminus of BMV MP is involved in the requirement for CP in cell-to-cell movement
      and plays a role in long-distance movement. Furthermore, the ability to spread
      locally and form virions is not sufficient for the long-distance movement of BMV.
      The roles of MP and CP in BMV movement are discussed.

PMID- 15166462
TI  - Significance of the 3'-terminal region in minus-strand RNA synthesis of Hibiscus
      chlorotic ringspot virus.
AB  - RNA-dependent RNA polymerase (RdRp) was solubilized from crude extracts of
      Hibiscus cannabinus infected by Hibiscus chlorotic ringspot virus (HCRSV), a
      member of the Carmoviridae. After treatment of the extracts with micrococcal
      nuclease to remove the endogenous templates, the full-length genomic RNA and the
      two subgenomic RNAs were efficiently synthesized by the partially purified RdRp
      complex in vitro. When the full-length RNAs of Potato virus X, Tobacco mosaic
      virus, Odontoglossum ringspot virus and Cucumber mosaic virus were used as
      templates, no detectable RNA was synthesized. Synthesis of HCRSV minus-strand RNA
      was shown to initiate opposite the 3'-terminal two C residues at the 3' end in
      vitro and in vivo. The CCC-3' terminal nucleotide sequence was optimal and
      nucleotide variations from CCC-3' diminished minus-strand synthesis. In addition,
      two putative stem-loops (SLs) located within the 3'-terminal 87 nt of HCRSV plus
      strand RNA were also essential for minus-strand RNA synthesis. Deletion or
      disruption of the structure of these two SLs severely reduced or abolished RNA
      synthesis. HCRSV RNA in which the two SLs were replaced with the SLs of Turnip
      crinkle virus could replicate in kenaf protoplasts, indicating that functionally
      conserved structure, rather than nucleotide sequence, plays an important role in
      the minus-strand synthesis of HCRSV. Taken together, the specific sequence CCC at
      the 3' terminus and the two SLs structures located in the 3'UTR are essential for
      efficient minus-strand synthesis of HCRSV.

PMID- 15166463
TI  - Standards for the assay of Creutzfeldt-Jakob disease specimens.
AB  - Assays for the agent of Creutzfeldt-Jakob disease (CJD) include measurement of
      infectivity in different animal systems, such as wild-type or transgenic mice,
      and detection of PrP(Sc) by different methods and formats. The various assays
      could be best calibrated against each other by use of uniform readily available
      materials, and samples of four human brains, two from sporadic CJD patients, one
      from a variant CJD patient and one from a non-CJD patient, have been prepared as
      10% homogenates dispensed in 2000 vials each for this purpose. Results of in
      vitro methods, particularly immunoblot assays, were compared in the first
      collaborative study described here. While dilution end-points varied, the minimum
      detectable volume was surprisingly uniform for most assays and differences in
      technical procedure, other than the sample volume tested, had no detectable
      systematic effect. The two specimens from sporadic CJD cases contained both type
      1 and type 2 prion proteins in approximately equal proportions. The materials
      have been given the status of reference reagents by the World Health Organization
      and are available for further study and assessment of other in vitro or in vivo
      assay procedures.

PMID- 15166464
TI  - Amyloid imaging probes are useful for detection of prion plaques and treatment of
      transmissible spongiform encephalopathies.
AB  - Diagnostic imaging probes have been developed to monitor cerebral amyloid lesions
      in patients with neurodegenerative disorders. A thioflavin derivative, 2-[4'
      (methylamino)phenyl] benzothiazole (BTA-1) and a Congo red derivative, (trans,
      trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) are
      representative chemicals of these probes. In this report, the two chemicals were
      studied in transmissible spongiform encephalopathies (TSE). Both BTA-1 and BSB
      selectively bound to compact plaques of prion protein (PrP), not only in the
      brain specimens of certain types of human TSE, but also in the brains of TSE
      infected mice when the probes were injected intravenously. The chemicals bound to
      plaques in the brains were stable and could be detected for more than 42 h post
      injection. In addition, the chemicals inhibited abnormal PrP formation in a
      cellular model of TSE with IC(50) values of 4 nM for BTA-1 and 1.4 micro M for
      BSB. In an experimental mouse model, the intravenous injection of 1 mg BSB
      prolonged the incubation period by 14 %. This efficacy was only observed against
      the RML strain and not the other strains examined. These observations suggest
      that these chemicals bind directly to PrP aggregates and inhibit new formation of
      abnormal PrP in a strain-dependent manner. Both BTA-1 and BSB can be expected to
      be lead chemicals not only for imaging probes but also for therapeutic drugs for
      TSEs caused by certain strains.

PMID- 15166465
TI  - Cationic phosphorus-containing dendrimers reduce prion replication both in cell
      culture and in mice infected with scrapie.
AB  - Over the last 30 years, many drugs have been tested both in cell culture and in
      vivo for their ability to prevent the generation of prions and the development of
      transmissible spongiform encephalopathies. Among the compounds tested, dendrimers
      are defined by their branched and repeating molecular structure. The anti-prion
      activity of new cationic phosphorus-containing dendrimers (P-dendrimers) with
      tertiary amine end-groups was tested. These molecules had a strong anti-prion
      activity, decreasing both PrP(Sc) and infectivity in scrapie-infected cells at
      non-cytotoxic doses. They can bind PrP and decrease the amount of pre-existing
      PrP(Sc) from several prion strains, including the BSE strain. More importantly,
      when tested in a murine scrapie model, the dendrimers were able to decrease
      PrP(Sc) accumulation in the spleen by more than 80 %. These molecules have a high
      bio-availability and therefore exhibit relevant potential for prion therapeutics
      for at least post-exposure prophylaxis.

PMID- 15166466
TI  - A comparative study on idiopathic pulmonary fibrosis and secondary diffuse
      parenchymal lung disease.
AB  - BACKGROUND AND AIMS: Clinical characteristics of patients diagnosed to have
      Diffuse parenchymal lung disease (DPLD) were evaluated in this study. DESIGN AND
      SETTING: Retrospective evaluation, a tertiary care center in South India.
      MATERIAL AND METHOD: Subjects diagnosed to have DPLD over a five-year period were
      included in this study. Data pertained to clinical characteristics and lab
      parameters were obtained. STATISTICAL CONSIDERATIONS: t- test for Mean values and
      chi-square test for comparing proportions were used. RESULTS: There were 73
      eligible patients included for evaluation. Secondary cause for DPLD was diagnosed
      in 40 (55%) and idiopathic pulmonary fibrosis (IPF) was diagnosed in 33 (45%).
      The mean age was 45+/-11 and 53+/-10 years, of these 5 (12%) and 17 (52%) were
      male subjects in the secondary DPLD and IPF group respectively. The mean age,
      dyspnoea, cough, clubbing and crepitations were noted to be higher in patients
      with IPF as compared to patients with secondary DPLD. Fifty patients were
      followed up for a mean of 13 months (28 secondary DPLD and 18 IPF). Follow up
      data was available in 46 patients. Of these subjects prednisone alone was
      initiated in 24 subjects and combination with azathioprine in 22. Subjective
      improvement in symptoms was noted in 29/46 (63%), 19 with secondary DPLD and 10
      with IPF. CONCLUSION: symptoms and signs were noted more frequently with IPF,
      subjective improvement to treatment was noted in 63% and the best response was
      noted among patients diagnosed to have sarcoidosis. A prospective trial is needed
      to study the long term prognosis and therapeutic response among Indian patients.

PMID- 15166467
TI  - The full moon and admission to emergency rooms.
AB  - OBJECTIVE: The purpose of this study was to investigate an ancient hypothesis;
      the moon effect might increase incidence of injuries and hence admission of
      patients with trauma to Emergency Rooms (ERs) on full moon days. METHODS: During
      thirteen months, 58000 trauma patients admitted in three hospitals that had the
      highest load of trauma patients in Tehran were studied. Due to lack of complete
      data, 3543 patients (6.1%) were excluded from the study, leaving 54457 cases for
      further analysis. We selected lunar calendar for our study, so dates of patients'
      admissions were converted to lunar months and three day- periods with 15th as
      middle day were defined as full moon days. RESULTS: In our study the number of
      trauma patients was not increased during the full moon days against other days of
      lunar month. Statistical analyses of data didn't exhibit a positive relation
      between full moon days and increasing of trauma patient admission to ERs. An
      association between assault and attempted suicide was not observed around the
      full moon days either. The results did not show significant reduction of GCS
      score of patients on full moon days and there was not any increase in severity of
      traumatic injury sustained during full moon days. CONCLUSIONS: It seems necessary
      to conduct studies regarding the probability of moon effect through on different
      database, geographic areas and for appropriate periods in order to reach a
      conclusive result.

PMID- 15166468
TI  - Mini laparotomy versus conventional laparotomy for abdominal hysterectomy: a
      comparative study.
AB  - BACKGROUND: Less traumatizing measures for hysterectomies are searched for to
      improve the recovery from surgery. AIM: Comparison of minilaparotomy abdominal
      hysterectomy with conventional abdominal hysterectomy in respect to per-operative
      and post-operative outcome and complications. SETTING AND DESIGN: In a medical
      college hospital patients undergoing abdominal hysterectomy were enrolled. It was
      a concomitant comparative study. METHODS AND MATERIAL: We are presenting our
      comparative data of 100 cases of minilaparotomy abdominal hysterectomy (group I,
      incision =< 6 cm) performed over last 4 years from January 1998 to December 2002
      and comparing the outcome with 99 cases of abdominal hysterectomy (group II,
      incision > 6 cm) done by traditional method over the same duration. STATISTICAL
      ANALYSIS USED: Chi-square and Fischer test with significance of p value being
      taken at 0.05 were used for categorical data, while student's t test was used for
      continuous data. RESULTS: Mean age and parity of patients were similar in the two
      groups. Incision was transverse in 100% cases in-group I and 22.2% cases in-group
      II. Estimated blood loss was significantly higher (354 ml) in group II in
      contrast to group I (240 ml). Blood transfusion was also required more commonly
      (22.2%) in-group II than in-group I (9%). Mean operative time was significantly
      more in-group II (90 minutes) than in group I (41 minutes). Mean hospital stay,
      day of mobility, starting oral diet and days of injectable analgesics required
      were higher in group II than in group I. Major complications were rare in both
      the groups, but minor complications were significantly higher in group II (40.4%)
      than in group I (26%). CONCLUSION: Minilaparotomy abdominal hysterectomy appears
      to be an attractive alternative to traditional abdominal hysterectomy with fewer
      complications.

PMID- 15166469
TI  - Spinal tuberculosis due to dissemination of atypical mycobacteria.
AB  - There has been an increase in disease caused by Non Tuberculous Mycobacteria
      (NTM) since the early 1980s. Though ubiquitous in environment, they may act as
      clinically important pathogens in various conditions. More importantly they are
      resistant to the conventional anti-tuberculous therapy (ATT) and respond to
      antibiotics such as quinolones and aminoglycosides and need an aggressive
      surgical intervention. Missing these atypical mycobacteria may lead to
      unnecessary administration of ATT and hence delay in proper management of the
      case. We report a case of spinal tuberculosis due to a Non Tuberculous
      Mycobacteria, M. fortuitum (Rapid grower). Relevant literature is also reviewed.

PMID- 15166471
TI  - Drug induced serious hepatic adverse reactions in a tertiary care centre: a five
      year retrospective analysis.

PMID- 15166470
TI  - Malignant struma ovarii: a case report and review of the literature.
AB  - A 45-year-old woman with papillary carcinoma arising in struma ovarii which
      involved one ovary without dissemination is presented. Total abdominal
      hysterectomy and bilateral salpingo-oophorectomy were performed.
      Histopathological examination revealed malignant struma ovarii of the papillary
      type. The flow cytometric analysis revealed an hypodiploid DNA content (DNA
      index:0.67). Since these are rare tumors, there is no universal exact protocol
      for the treatment and follow-up of patients with malignant struma ovarii. More
      data are needed to determine the prognosis and management in preferring mode of
      therapy.

PMID- 15166472
TI  - Awareness of computer-use related health risks in software companies in
      Bangalore.

PMID- 15166473
TI  - Iron deficiency anemia--Part III.

PMID- 15166474
TI  - Granulocyte extravasation and recruitment to sites of interstitial inflammation
      in patients with renal failure.
AB  - BACKGROUND: We have shown that leukocytes collected from sites of interstitial
      inflammation in patients on hemodialysis have a disturbed expression of CD11b
      compared to cells from healthy subjects. The aim of the present study was to
      study adhesion molecule expression on granulocytes in the peripheral circulation
      and at sites of interstitial inflammation in patients with renal failure.
      METHODS: Two skin blisters were raised in 10 patients and 19 healthy subjects and
      interstitial exudates collected (0 h). Skin chambers were applied and exposed to
      buffer or serum for 10 h in order to induce an intermediate and an intense
      interstitial inflammation. Cells and blister fluid were collected for
      determination of leukocyte count, CD11b/CD62L expression, interleukin-8 (IL-8)
      concentration in the interstitium and blister activity in terms of CD11b up
      regulation. RESULTS: At the sites of intermediate and intense inflammation,
      granulocytes from patients with renal failure showed significantly higher
      expression of CD62L (p < 0.01 and p < 0.001, respectively) and significantly
      lower expression of CD11b (p < 0.0001 and p < 0.0001, respectively) compared to
      corresponding cells from healthy subjects. The interstitial concentration of IL-8
      was significantly lower at the sites of intermediate (p < 0.005) and intense
      inflammation (p < 0.05) in patients with renal failure compared to in healthy
      subjects. In order to explore whether the decreased CD11b expression observed in
      patients is due to the interstitial milieu, blister exudates from patients and
      healthy subjects were incubated with leukocytes from healthy blood donors.
      Blister exudates from patients had a similar capacity to mobilize CD11b on
      granulocytes in vitro compared with blister exudates from healthy subjects. There
      was no consistent correlation between the expression of adhesion molecules on
      granulocytes in the interstitium and the concentration of IL-8 or the total
      interstitial concentration of chemotactic mediators. CONCLUSION: Constitutive
      cellular determinants are probably involved in the disturbed expression of
      adhesion molecules on granulocytes at sites of interstitial inflammation in
      patients with renal failure.

PMID- 15166475
TI  - Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase
      of acute pancreatitis.
AB  - BACKGROUND: In acute pancreatitis (AP), several studies indicated that the
      balance between pro- and anti-inflammatory mediators is more important than the
      levels of proinflammatory response alone. This balance may be reflected by the
      expression of monocyte histocompatibility leukocyte antigen (HLA)-DR, with a low
      concentration indicating an excess of anti-inflammatory stimuli and relative
      immunodeficiency. We investigated the time course of HLA-DR expression in the
      early phase of AP and the relationship to markers of inflammation, severity of
      the disease, organ function, septic complications and outcome during AP. METHODS:
      The expression of HLA-DR on peripheral monocytes was measured in 74 patients by
      flow cytometry and serum IL-6 was determined by using an immunochemiluminescence
      assay obtained 24 h, 48 h, 72 h, 7 days, 10 days and 14 days after admission in
      parallel with clinical data collection. 25 patients had mild disease (grade 1),
      31 had severe disease but recovered without organ failure (grade 2) and 18 had
      severe disease and developed organ failure (grade 3). RESULTS: In 49 patients
      with severe disease, 11 patients suffered from sepsis, and 3 of them died during
      the hospital stay. During the first 14 days of AP, the percentage of HLA-DR in AP
      was significantly below the normal range of healthy subjects, it dropped to the
      lowest level on day 3, but then gradually recovered from the prophase depression.
      The HLA-DR expression decreased in the order grade 3 < grade 2 < grade 1 (p <
      0.001). We also observed a significant inverse correlation between the percentage
      of HLA-DR+ and AP severity as assessed by APACHE-II scores (r = 0.754, p < 0.001)
      and MODS score (r = 0.675, p < 0.001). The peak of systemic inflammatory
      reaction, documented by maximum serum concentration of CRP, coincided with the
      nadir of HLA-DR suppression. Moreover, IL-6 and CRP serum concentrations were
      inversely correlated with HLA-DR expression over the entire observation period.
      Persistent HLA-DR suppression and a second decrease in HLA-DR expression are
      associated with septic complications and poor outcome. CONCLUSION: Immune
      suppression develops early and rapidly in patients with AP, and the degree is
      parallel with the severity of the disease. Decreases in HLA-DR expression
      occurred simultaneously with signs of hyperinflammation in the early phase of AP,
      and persistent HLA-DR suppression and a second decrease in HLA-DR expression are
      associated with septic complications and poor outcome.

PMID- 15166476
TI  - Expression of a human SOCS protein, HSOCP-1, in peripheral blood eosinophils from
      patients with atopic dermatitis.
AB  - To identify new genes related to atopic dermatitis (AD), we screened for
      differentially expressed genes in peripheral blood eosinophils derived from AD
      patients and healthy volunteers. RNA was prepared from peripheral blood
      eosinophils obtained from both AD patients and healthy volunteers, and the
      expression of various genes was monitored using fluorescent differential display
      and real-time RT-PCR. One of the expressed sequence tags (ESTs) was expressed at
      a significantly higher level in AD patients than in healthy volunteers. A full
      length cDNA was identified that encoded a human suppressor of cytokine signaling
      (SOCS) protein, HSOCP-1, also named hASB-8. The expression of HSOCP-1 was
      increased in cultured peripheral blood eosinophils after IL-4 stimulation, and
      overexpression of HSOCP-1 caused cell death in an eosinophil cell line,
      AML14.3D10. p34(SEI-1) was identified as a HSOCP-1-interacting protein by a yeast
      two-hybrid system. It is a protein that also interacts with the cyclin-dependent
      kinase inhibitor p16(INK4), suggesting that HSOCP-1 is involved in cell cycle
      control and apoptosis.

PMID- 15166477
TI  - Correlation of allergen-induced IL-5 and IL-13 production by peripheral blood T
      cells of asthma patients.
AB  - BACKGROUND: Helper T cells and T cell cytokines are implicated in allergic
      disorders such as asthma and atopic dermatitis (AD). We reported enhanced
      interleukin-5 (IL-5) production by peripheral blood T cells of asthmatic
      patients. Production of cytokines, particularly IL-5 and IL-13, by peripheral
      blood mononuclear cells (PBMC) obtained from bronchial asthma (BA) and AD
      patients was investigated in the present study. METHODS: PBMC were cultured in
      the presence of either polyclonal activator, phorbol ester plus Ca2+ ionophore or
      Dermatophagoides farinae (Df) antigen. The resulting supernatants were assayed
      for IL-4, IL-5, and IL-13 by specific ELISAs. RESULTS: IL-5 and IL-13 production
      in response to Df antigen is significantly higher in allergic groups compared to
      control subjects. IL-5 responses induced by Df antigen were strongly correlated
      with IL-13 responses. CONCLUSION: In spite of IL-13 gene proximity to IL-4 gene,
      IL-5 production was more strongly correlated to IL-13 production in the BA group,
      suggesting a common control mechanism that regulates the IL-5 and IL-13 gene.

PMID- 15166478
TI  - Molecular mechanisms of repression of eotaxin expression with fluticasone
      propionate in airway epithelial cells.
AB  - BACKGROUND: Glucocorticoids are known to repress the expression of CC chemokine
      eotaxin in airway epithelial cells. We focused our study on the molecular
      mechanisms of the glucocorticoid, fluticasone, in the inhibition of the
      expression of the eotaxin gene in the cells. METHODS: The airway epithelial cell
      line, BEAS-2B, was stably transfected with signal transducers and activators of
      transcription 6 (STAT6)-expressing vector and used in the following experiments
      to clarify the function of STAT6. Levels of eotaxin mRNA and protein expression
      were determined with RT-PCR and ELISA. Mechanisms of transcriptional regulation
      were assessed by the electrophoretic mobility shift assay and dual luciferase
      assay using eotaxin promoter-luciferase reporter plasmids. RESULTS: Fluticasone
      significantly inhibited the induction of eotaxin protein stimulated with TNF
      alpha and IL-4 in the cells. Fluticasone also repressed the induction of eotaxin
      mRNA with these stimuli. It partially inhibited the activity of eotaxin promoter;
      however, it did not inhibit the nuclear translocation and binding of
      transcription factors, nuclear factor-kappa B (NF-kappaB) or STAT6, to the DNA
      derived from the proximal promoter region of the eotaxin gene. Moreover, the
      inhibitory effect was also conserved in the experiments using the reporter
      plasmid of which the putative glucocorticoid-responsive element was mutated.
      CONCLUSIONS: Fluticasone inhibits the expression of eotaxin gene in airway
      epithelial cells in part through repression of the transcription. However, the
      mechanisms depend neither on the inhibition of transcription factors'
      translocation into nuclei nor the function of the putative glucocorticoid
      responsive element in the promoter, indicating that other mechanisms would be
      related to the transcriptional repression of the eotaxin gene in airway
      epithelial cells.

PMID- 15166479
TI  - Immunotherapy attenuates eosinophil transendothelial migration induced by the
      supernatants of antigen-stimulated mononuclear cells from atopic asthmatics.
AB  - BACKGROUND: Eosinophil transendothelilal migration across vascular endothelial
      cells is an initial step of eosinophil accumulation in allergic inflammation.
      There is increasing evidence that specific immunotherapy (SIT) modulates the
      production of inflammatory molecules from mononuclear cells. OBJECTIVE: The
      present study was undertaken to examine whether SIT modifies eosinophil
      transendothelial migration induced by the supernatants of antigen-stimulated
      mononuclear cells from atopic asthmatics. METHODS: Dermatophagoides farinae (Df)
      sensitive mild persistent asthmatics were divided into a SIT-treated group and a
      control group. Peripheral blood mononuclear cells (PBMC) were isolated before and
      after SIT using the rush protocol, and cultured for 96 h at 37 degrees C in the
      presence or absence of Df antigen. Eosinophils were isolated from the blood of
      healthy subjects, and put on transwell filters coated with pulmonary
      microvascular endothelial cell monolayers stimulated with IL-4 plus TNF-alpha.
      The supernatants of PBMC were applied to the lower compartment and the
      transmigration of eosinophils was examined. RESULTS: Df stimulation of PBMC
      resulted in an augmentation of eosinophil transendothelial migration. This
      enhancement was abrogated following SIT. In the control group, the antigen
      induced effect on eosinophil transmigration did not show an interval change.
      CONCLUSION: SIT attenuates eosinophil transendothelial migration induced by
      antigen-stimulated mononuclear cells.

PMID- 15166480
TI  - Tyk2 is essential for IFN-alpha-induced gene expression in mast cells.
AB  - Mast cells are recognized not only as the major effector cells of type I
      hypersensitivity reactions but also as an important player of innate immune
      response against bacterial infection. Type I IFNs are also involved in the
      response against bacterial infection. However, the role of type I IFNs and their
      associated Janus kinase Tyk2 in mast cell functions remains to be determined. In
      this study, we addressed this issue using Tyk2-deficient (Tyk2(-/-)) bone marrow
      derived mast cells (BMMCs). When BMMCs from wild-type (WT) mice were stimulated
      with IFN-alpha, they expressed mRNA for IFN-gamma-inducible protein 10 (IP-10)
      and monocyte chemoattractant protein-5 (MCP-5). Interestingly, IFN-alpha-induced
      expression of IP-10 and MCP-5 was severely decreased in Tyk2(-/-) BMMCs. In
      addition, IFN-alpha-induced Stat1 phosphorylation was decreased in Tyk2(-/-)
      BMMCs. On the other hand, IFN-alpha-induced Stat1 phosphorylation and IP-10 and
      MCP-5 expression were normal in Tyk2(-/-) fibroblasts. These results indicate
      that IFN-alpha induces the expression of TNF-alpha and the chemokines IP-10 and
      MCP-5 in mast cells and thatTyk2 plays a nonredundant role in IFN-alpha signaling
      in mast cells.

PMID- 15166481
TI  - Peroxisome proliferator-activated receptor gamma regulates eosinophil functions:
      a new therapeutic target for allergic airway inflammation.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that regulates lipid metabolism and glucose homeostasis. PPARgamma is
      not only highly expressed in adipose tissue but also in cells involved in the
      immune system, and it exerts anti-inflammatory activities. We showed that
      eosinophils, a major inflammatory cell in allergic inflammation, express
      PPARgamma. PPARgamma negatively modulates eosinophil functions, such as survival,
      chemotaxis, antibody-dependent cellular cytotoxicity and degranulation. Recently,
      three independent groups have demonstrated that PPARgamma agonists inhibit airway
      inflammation in an animal model of asthma. This evidence suggests that PPARgamma
      agonists may be a new therapeutic modality for the treatment of allergic diseases
      including asthma.

PMID- 15166482
TI  - Dual signaling and effector pathways mediate human eosinophil activation by
      platelet-activating factor.
AB  - Platelet-activating factor (PAF) induces various cellular functions in
      eosinophils including chemotaxis, adhesion, superoxide anion (O2-) production,
      and degranulation. While PAF shares many biological effects with other
      chemotactic factors such as N-formyl-methionyl-leucyl-phenylalanine, complement
      fragments, and lipid mediators, PAF is unique in that its action is relatively
      resistant to pertussis toxin (PTX), and in activating eosinophils more strongly
      than neutrophils. In this review we consider how PAF might activate human
      eosinophils in preference to neutrophils, and discuss possible mechanisms of PAF
      induced activation of human eosinophils via two distinct signaling and effector
      pathways. Recently we analyzed O2- production by eosinophils using a sensitive,
      real-time chemiluminescence method. Our results showed that in human eosinophils
      PAF activates two distinct signaling and effector pathways coupled to the PAF
      receptor: one linked to PTX-sensitive G protein(s) and another to PTX-resistant G
      protein(s), phosphatidylinositol 3-kinase, and cellular adhesion. This activation
      of two different G proteins by the eosinophil PAF receptor may explain the strong
      and diverse biological responses of human eosinophils to PAF.

PMID- 15166483
TI  - GH and cortisol response to glucagon administration in short children.
AB  - OBJECTIVE: To establish whether there is a link between GH status and glucose
      response to glucagon and to identify determinants of maximum GH and cortisol
      concentrations. METHODS: 95 children referred for assessment of short stature,
      slow growth or suspected hypothalamo-pituitary dysfunction were assigned to
      normal, organic GH-deficient or non-organic GH-deficient groups on the basis of
      history, GH response and MRI findings. RESULTS: Baseline glucose and glucose
      nadir were related to age in normal children, but the glucose response to
      glucagon was not linked to GH status. Peak GH response was positively related to
      age in prepubertal children and peak cortisol was inversely related to age.
      CONCLUSIONS: GH status is not a major determinant of the glucose response to
      glucagon. There is a relationship between age and the GH/cortisol response in
      short normal children.

PMID- 15166484
TI  - IGFs, IGFBPs, IGF-binding sites and biochemical markers of bone metabolism during
      differentiation in human pulp fibroblasts.
AB  - OBJECTIVE: To investigate the role of the insulin-like growth factors (IGF)
      system during the differentiation of human pulp-derived fibroblasts (HPF).
      METHODS: Primary HPF were cultured for 24 days in DMEM medium with IGF-I or IGF
      II (50 ng/ml each). Cell growth and morphology, alkaline phosphatase (ALP)
      activity, the concentration of free deoxypyridinoline (DPD), IGF-I, -II, IGFBP-2
      and -3 were studied. The number of (125)I-IGF-I binding sites was estimated by
      Scatchard analysis. RESULTS: Light-microscopically visible nodules emerged during
      differentiation. Simultaneously, the ALP activity increased steadily between days
      8 and 24, while the DPD concentration decreased by about 50%. The HPF produced
      high concentrations of IGF-II (2.00-1.30 microg/10(6) cells) but low IGF-I, IGFBP
      2. IGFBP-2 was not changed, IGFBP-3 increased by 65% during differentiation. The
      number of IGF binding sites increased from 8,500 +/- 55 per cell (day 8) up to
      22,000 +/- 570 (day 24). CONCLUSION: The increasing number of IGF-binding sites
      accompanied by alterations in the biochemical bone markers during the
      differentiation of HPF suggests an autocrine/paracrine role for the IGFs in the
      formation of dentinal hard tissue.

PMID- 15166485
TI  - Liver transplantation in cirrhotic patients with small hepatocellular carcinoma:
      an analysis of pre-operative imaging, explant histology and prognostic histologic
      indicators.
AB  - BACKGROUND: In recent years, liver transplantation in patients with
      hepatocellular cancers and cirrhosis has been restricted to those with small
      cancers (<5 cm for solitary and <3 cm for multifocal HCC with <3 nodules). The
      selection of patients for liver transplantation is based on pre-operative
      imaging. The accuracy of imaging correlated with explant histology and the effect
      of tumour stage has not been evaluated in this selected population. METHODS: In
      this study, prospectively collected data for 30 patients who underwent orthotopic
      liver transplantation for cirrhosis complicated by small hepatocellular carcinoma
      (HCC) at a single centre have been reviewed with the aim of correlating
      radiological findings, explant histology and patient outcome. Patients who
      underwent orthotopic liver transplantation between 1995 and 1999 had plain and
      contrast-enhanced dual-phase spiral CT (DCT) scans of the liver. Patients
      suspected of having HCC on CT scan or due to elevated serum alpha-fetoprotein
      underwent iodized oil CT (IOCT). Following transplantation, the explanted liver
      was serially sectioned at 10-mm intervals and examined by a pathologist blinded
      to the results of imaging. Data collected prospectively on imaging and histology
      were compared with outcome data. The median period of follow-up was 1,139 days
      (range 690-1,955 days) after transplantation. All patients were followed up by
      clinical assessment, assessment of serum alpha-protein levels and imaging when
      indicated. RESULTS: All the patients transplanted fulfilled the selective
      criteria on the basis of imaging (solitary HCC <5 cm in diameter or multifocal
      HCC <3 cm in diameter with <3 nodules). Of the 30 patients transplanted, 46 HCCs
      were detected on explant histology with a median size of 24 mm (range 6-75 mm).
      Ten patients had multifocal disease (median number of lesions 2, range 2-4). No
      significant difference was observed between IOCT and DCT with regards to the
      sensitivity (67.4 vs. 68%) and specificity (78.97 vs. 88.6%) of detecting HCCs.
      IOCT had a positive predictive value of 78.9% as compared to 82.8% for DCT. IOCT
      had an overall sensitivity of 40% as compared to 30% for DCT in detecting
      multifocal disease (not significant). Histological assessment of the explanted
      livers showed that 8 patients had well-, 17 moderate and 5 poorly differentiated
      HCCs. Tumour size and the presence of multifocal disease did not influence
      survival in this study. Microvascular invasion was more common with larger
      tumours (from 38% with lesions less than 40 mm in diameter to 60% with lesions
      >40 mm in diameter; p < 0.01) and with moderately (29.4%) or poorly
      differentiated (60%) HCCs than well-differentiated HCC (12.5%) (p < 0.04 and 0.01
      for well- vs. moderately and poorly differentiated HCC, respectively).
      Microvascular invasion on explant histology was associated with poor survival. Of
      the 17 transplant recipients without vascular invasion, 15 were alive at 1 and 2
      years in comparison to 7 of 9 with microscopic vascular invasion (p < 0.01). Four
      patients died in the post-transplant period due to recurrent HCC. Overall
      survival [after excluding early post-transplant sepsis-induced deaths (n = 4)] at
      1 year was 83.3%. CONCLUSIONS: Selective criteria for transplantation of HCC in
      cirrhosis are associated with a 1-year and 3-year survival rate of 73.3%
      (including early post-transplant sepsis-induced deaths). IOCT and DCT are similar
      in their ability to detect unifocal or multifocal HCC. Tumour size and number are
      not predictive of recurrence with these selective criteria, but microscopic
      vascular invasion is a bad prognostic factor.

PMID- 15166486
TI  - Migratory necrolytic dermatitis presenting after cephalosporin administration in
      a patient with a pancreatic head mass.
AB  - Migratory necrotizing dermatitis is one of the most distressing presenting
      symptoms of glucagonomas. This rare functioning pancreatic endocrine tumor is
      third in incidence after insulinomas and gastrinomas and is often malignant at
      the time of diagnosis. Elevated serum glucagon levels cause decreased amino acid
      levels which is believed to be the principal cause of the dermatitis. Other
      symptoms include anemia, visual scotomata and mild diabetes mellitus. Medical
      treatment alone including octreotide and amino acid supplementation has been
      reported to eliminate the dermatitis. Nonetheless, surgical resection or
      debulking remains the definitive treatment when possible. Because of its rarity,
      diagnosis may be delayed by years accounting for the high rate of metastasis at
      presentation. Reported here is the case of a 77-year-old man who presented with a
      migratory necrotizing dermatitis after antibiotic treatment and whose diagnosis
      of a glucagonoma was then delayed for over 1 year.

PMID- 15166487
TI  - Expression of reg I alpha protein in human gastric cancers.
AB  - BACKGROUND/AIMS: Although regenerating gene(Reg) I alpha protein has a trophic
      effect on gastric epithelial cells, it is unclear whether Reg I alpha protein and
      its receptor are involved in gastric carcinogenesis. Therefore, we investigated
      the Reg I alpha protein expression in human gastric cancers and assessed its
      relationship to clinicopathological factors. METHODS: Sixty-one gastric cancer
      specimens were examined, using immunohistochemistry, for Reg I alpha protein,
      p53, and proliferating cell nuclear antigen. The expression of both Reg I alpha
      and Reg receptor mRNA was examined in seven human gastric cancer cell lines
      (MKN1, MKN28, MKN45, MKN74, KATOIII, GCIY, and AGS) by reverse transcription
      polymerase chain reaction and Northern blot analysis. RESULTS: Twenty-three
      (37.7%) of the 61 gastric cancer tissues samples were positive for Reg I alpha
      protein. The Reg I alpha expression was significantly related to the presence of
      lymphatic invasion but not to tumor size, tumor stage, Lauren's classification,
      presence of venous invasion, lymph node metastases, or p53 overexpression.
      Gastric cancers positive for Reg I alpha protein showed a significantly higher
      proliferating cell nuclear antigen labeling index than negative ones. The
      expression of both Reg I alpha and Reg receptor mRNA was detected in all seven
      gastric cancer cell lines. CONCLUSION: Reg I alpha protein may play a role in the
      development of gastric cancers.

PMID- 15166488
TI  - Irritable bowel syndrome and bronchial hyperresponsiveness: is there a link?
AB  - BACKGROUND/AIM: Many studies have demonstrated a high prevalence of bronchial
      hyperresponsiveness in patients with irritable bowel syndrome (IBS). The aim of
      this 24-month prospective study was to evaluate the prevalence of IBS in
      asthmatic patients. METHODS: We analyzed 623 asthmatic patients that were
      evaluated for body mass index, sex, and age before undergoing both a methacholine
      challenge test (MCHt) and skin prick tests. RESULTS: We found that 276 asthmatic
      patients (44.3%) were positive on the MCHt, while 347 (55.7%) were negative. We
      also found that 27 (9.7%) of the 276 patients with a positive MCHt and 44 (12.7%)
      of the 347 patients with a negative MCHt were affected by IBS. Therefore, there
      was no statistically significant difference between positive MCHt tests and IBS.
      The PC(20) (mean provocation concentration of methacholine producing a 20%
      reduction in forced expiratory volume in 1 s < or =16 mg/ml) in all patients
      tested was 8.64 +/- 2.58 mg/ml, being 8.75 +/- 2.52 and 8.55 +/- 2.32 mg/ml for
      males and females, respectively. CONCLUSIONS: These results do not demonstrate a
      relationship between MCHt and IBS. However, a relationship might still exist in a
      subpopulation of patients whose symptoms worsen by stress.

PMID- 15166490
TI  - Impact of residual renal function on volume status in chronic renal failure.
AB  - During the past few years, it has become increasingly evident that residual renal
      function (RRF) is an important and independent predictor of poor outcome in
      patients with chronic kidney disease (CKD). Although the causes of this
      observation are not fully understood, it appears that the loss of RRF impairs
      both fluid removal and clearance of solutes, which in turn leads to uremic
      toxicity and increased morbidity and mortality. There is increasing evidence that
      patients with CKD develop signs of fluid overload already in the early phases of
      the disease, and this may be a stimulus for inflammatory activation. Recently, an
      inflammatory component was identified in uremic atherosclerotic and non
      atherosclerotic cardiovascular disease (CVD), which have been consistently
      associated with poor clinical outcome in patients with CKD. Signs of systemic
      inflammation occur in parallel to the impairment in renal function, and the
      pathophysiology is most likely multifactorial, including a decrease in cytokine
      clearance, advanced glycation end-product accumulation, oxidative stress, and
      principal fluid overload. Additionally, inflammation seems to be a predictor of
      accelerated loss of renal function. In this article, we discuss the evidence
      showing that patients with CKD generally have fluid overload, the mechanisms by
      which impaired renal function may lead to a chronic inflammatory state, and the
      available information linking fluid overload to accelerated loss of renal
      function and CVD through inflammation. Inflammation may lead to the development
      of complications of CKD, in particular CVD, but on the other hand may also lead
      to a faster progression of renal disease. Strategies aiming to reduce fluid
      overload may be useful to reduce cardiovascular morbidity and mortality, but also
      preserve RRF.

PMID- 15166489
TI  - The interaction between heart failure, renal failure and anemia - the cardio
      renal anemia syndrome.
AB  - BACKGROUND: Many patients with congestive heart failure (CHF) have chronic kidney
      insufficiency (CKI) and anemia. AIMS: The purpose of this review is to clarify
      the relationship between these three factors and to study the effect of
      correction of anemia in CHF and CKI. FINDINGS: Anemia, CHF and CKI are each
      capable of causing or worsening each other. Thus they form a vicious circle which
      can result in progressive CHF, CKI and anemia. Aggressive therapy of CHF, CKI and
      control of the associated anemia with erythropoietin and i.v. iron can prevent
      the progression of CHF and CKI, reduce hospitalization, and improve quality of
      life. CONCLUSION: CHF patients are a major source of end-stage renal failure
      patients and deserve special attention. If treated well and early, progressive
      heart failure and renal failure can be prevented. Cooperation between
      nephrologists, cardiologists, and other internists will improve the care of all
      three conditions and prevent their progression.

PMID- 15166491
TI  - Impact of serum parathyroid hormone concentration and its regulatory factors on
      arterial stiffness in patients undergoing maintenance hemodialysis.
AB  - BACKGROUND: Cardiovascular mortality is extremely high in patients on
      hemodialysis. Among a variety of pathophysiological conditions, deranged calcium
      homeostasis including secondary hyperparathyroidism may be one of the factors
      contributing to cardiovascular disease in patients on hemodialysis. This study
      was designed to evaluate the role of the serum parathyroid hormone (PTH)
      concentration and its regulatory factors in serum on arterial stiffness in
      patients on maintenance hemodialysis. METHODS: Arterial stiffness was assessed by
      pulse wave velocity (PWV) in 73 non-diabetic patients undergoing maintenance
      hemodialysis. At the same time, serum concentrations of calcium, phosphate, and
      intact PTH were measured. RESULTS: Single regression analyses revealed that
      arterial PWV was positively correlated with age (r = 0.505, p < 0.0001), systolic
      blood pressure (r = 0.250, p = 0.043), and pulse pressure (r = 0.306, p = 0.012).
      It was inversely correlated with the serum phosphate concentration (r = -0.240, p
      = 0.041) and the duration of hemodialysis treatment (r = -0.343, p = 0.003), but
      not with serum concentrations of calcium and intact PTH or the calcium x
      phosphate product in serum. By multiple regression analysis age was found to be
      the most significant variable affecting arterial PWV, and the duration of
      hemodialysis treatment negatively influenced arterial PWV. CONCLUSION: Age is an
      independent risk factor for arterial stiffness in patients on maintenance
      hemodialysis, and the serum PTH concentration and its regulatory factors in the
      serum are not.

PMID- 15166492
TI  - Increased levels of pregnancy-associated plasma protein A are associated with
      mortality in hemodialysis patients: preliminary results.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic indicator of
      acute coronary syndrome. This protein is elevated in hemodialysis (HD) patients
      and is closely related to inflammation and oxidative stress. The aim of our pilot
      study was to find out whether PAPP-A is related to mortality in HD patients. 40
      HD patients in a stable clinical state (20 men and 20 women, mean age 69 +/- 12
      years) were enrolled in the study and followed up for 20 months. PAPP-A was
      assessed immunochemically (TRACE method) in serum samples (before the HD session)
      at the beginning of the observation period. During the follow-up, 22 patients
      died, 15 of them due to cardiovascular events. PAPP-A levels were significantly
      higher in the patients who died, compared to living HD patients: 26.8 (21.6-36.8)
      vs. 20 (14.9-26.6) mU/l, p = 0.034. PAPP-A could also be a new prognostic marker
      in hemodialysis patients, probably due to its close association with
      cardiovascular risk. More extensive studies are required to confirm this
      hypothesis.

PMID- 15166493
TI  - VEGF and endostatin levels in wound fluid and plasma after breast surgery.
AB  - Angiogenesis is essential for wound repair after surgical trauma. Vascular
      endothelial growth factor (VEGF) and endostatin are endogenous angiogenic factors
      involved in the initiation and completion of angiogenesis. The aim of this study
      was to examine the local and systemic VEGF and endostatin profiles in patients
      undergoing surgery for benign and malignant breast processes. A total of 16
      patients with or without cancer underwent breast surgery. Group I: eight patients
      with primary breast cancer underwent a simple or radical mastectomy according to
      Madden including dissection of axillary lymph nodes. Group II: eight healthy
      female-to-male transsexuals underwent subcutaneous mastectomy. VEGF and
      endostatin levels in plasma and wound fluid were determined. In both groups VEGF
      levels in wound fluid were significantly higher compared to postoperative plasma
      levels, whereas wound fluid endostatin levels were lower than plasma levels and
      decreased progressively after surgery. In both groups plasma VEGF and endostatin
      levels did not change significantly before and after surgery. The local VEGF
      increase and endostatin decrease observed immediately after surgery appears to be
      a physiological response to operative trauma, which can be studied more
      profoundly in locally generated fluid than in blood. This process did not seem to
      be influenced by the type of process (cancerous or non-cancerous) involved in the
      surgical intervention.

PMID- 15166494
TI  - Novel function of ascorbic acid as an angiostatic factor.
AB  - Endothelial permeability is increased by vascular endothelial cell growth factor
      and decreased by antioxidants. Whether or not l-ascorbic acid (Asc), which
      decreases endothelial permeability by stimulating the endothelial barrier
      function, is anti-angiogenic (angiostatic) remains unknown. We examined the role
      of Asc on angiogenesis using two assay systems. At first, the potential role of
      Asc on four steps of angiogenesis was investigated in cultured bovine
      microvascular endothelial cells. Asc inhibited the formation of vessel-like
      tubular structures of endothelial cells cultured on Matrigel; however, it did not
      decrease the activity of plasminogen activator (PA), which creates the space into
      which vascular vessels extend. Furthermore, even at high concentrations, Asc did
      not inhibit either the proliferation or migration of endothelial cell cultures.
      Secondly, whether Asc inhibited in vivo angiogenesis or not was studied on chick
      chorioallantoic membrane (CAM) during the 4-6 days of embryogenesis when
      neovascularization is rapid. It also revealed that angiogenesis was dose
      dependently inhibited by Asc from 0.5 micro mol/CAM with half-maximal inhibition
      at 2.5 micro mol/CAM. Because it was previously reported that the endothelial
      barrier function decreases permeability via the stimulation of collagen synthesis
      induced by Asc, we treated CAM with the inhibitor of collagen synthesis, l
      azetidine 2-carboxylic acid (AzC). This compound partially attenuated the
      angiostatic function of Asc on CAM. To understand the involvement of an
      antioxidant activity in the angiostatic function of Asc, we further examined the
      effect of glutathione (GSH), which is an endogenous antioxidant, on angiogenesis
      in CAM and endothelial cells. GSH inhibited CAM angiogenesis, as well as the
      formation of vessel-like tubular structures of endothelial cell cultures on
      Matrigel. Both Asc and GSH inhibited hydrogen peroxide (H(2)O(2)) induced tubular
      morphogenesis. These findings suggest that Asc affects angiogenesis through both
      its antioxidant properties and the stimulation of collagen synthesis. As the
      angiostatic activity of Asc may be one of the many effects involved in host
      resistance to the growth or invasiveness of solid cancer, it may be useful as a
      supplementary therapy in various angiogenic diseases.

PMID- 15166496
TI  - Platelets and granulocytes, in particular the neutrophils, form important
      compartments for circulating vascular endothelial growth factor.
AB  - The measurement of circulating vascular endothelial growth factor (VEGF) levels
      as a prognostic factor will gain increasing relevance in the diagnosis and
      evaluation of treatment in cancer patients. Angiogenesis is an absolute
      requirement in tumour growth and metastatic disease. In the present study data
      are presented which indicate that circulating VEGF mainly resides in peripheral
      blood cells. In 15 healthy volunteers we demonstrated that approximately 34% of
      the circulating VEGF resides in platelets and approximately 11% in patients with
      cancer ( n = 4). An important part namely 58% in healthy volunteers and 69% in
      patients with cancer of the total circulating VEGF is contained in granulocytes,
      particular in the neutrophils, as confirmed by fluorescence-activated cell
      sorting (FACS). Also an increased VEGF level per granulocyte is found in patients
      with cancer (77 microg VEGF/l) compared with the healthy volunteers (164 microg
      VEGF/l). In contrast only 2% was present in plasma. The biological significance
      of platelet- or granulocyte-derived VEGF is not yet known. Liberation of VEGF
      from these compartments could well be of importance for tumour angiogenesis.
      Therefore, future studies on the clinical value of circulating VEGF as a
      prognostic factor in cancer patients should include measurements of VEGF in
      peripheral blood cells.

PMID- 15166495
TI  - 17 beta -estradiol-mediated vessel assembly and stabilization in tumor
      angiogenesis requires TGF beta and EGFR crosstalk.
AB  - It is widely established that angiogenesis is required during tumor progression.
      Emerging data, suggests that estrogens can mediate endothelial proliferation and
      differentiation. We investigated the role of estrogens in the formation and
      stabilization of capillary-like structures, and identified 17 beta -estradiol
      driven pathways involved in vessel assembly. We show that estrogens induce MCF7
      breast cancer cells to secrete TGF beta 1. In addition, TGF beta cross talks with
      EGFR signaling pathway with concomitant up-regulation of EGFR ligand, TGF alpha,
      promoting cord-like formations in HUVEC cultures. The action of 17 beta 
      estradiol was not restricted to endothelium, since 17 beta -estradiol also
      stimulated recovery and migration of a smooth muscle cell line (FLTR) to injured
      areas again by the cross talk between these two signaling pathways. Finally,
      given the relevant role of 17 beta -estradiol in vessel stabilization, co
      cultures of HUVEC and FLTR cells were established in the presence of 17 beta 
      estradiol or TGF beta 1. By blocking TGF beta or EGFR signaling, we demonstrate
      that 17 beta -estradiol promoted vessel stabilization through the interplay of
      TGF beta 1 and EGFR signaling transduction pathways. Our data suggest that
      estrogen mediates endothelial cell stabilization and vessel assembly. These
      vessel protective effects involve TGF beta 1 and EGFR signaling transduction
      pathways.

PMID- 15166497
TI  - Angiogenesis is not mediated by prostate cancer neuropeptides.
AB  - Once metastatic, prostate cancer (CaP) treatment options are limited to androgen
      withdrawal. In this environment, the cells often develop an androgen independent
      state resulting in patient demise. It has been shown that during this transition,
      CaP cells transdifferentiate to neuroendocrine cells, which produce
      neuropeptides. These neuropeptides have a mitogenic effect on surrounding CaP
      cells. Previous observations suggest that endothelial cells may show a similar
      mitogenic response to neuropeptides, implicating angiogenesis in the progression
      of CaP. We stimulated human umbilical endothelial cells (HUVECs) with the
      neuropeptides bombesin and neurotensin and measured proliferation, migration,
      cell tube formation, and tyrosine kinase activation. In our studies, neurotensin
      and bombesin did not stimulate HUVEC proliferation, migration, nor tube
      formation. Although HUVECs express the non-receptor tyrosine kinases Fak, Src,
      and Etk which mediate neuropeptide signaling in CaP, they are not activated by
      neuropeptides in HUVECs.

PMID- 15166498
TI  - Increased expression of VEGF-receptors (FLT-1, KDR, NRP-1) and thrombospondin-1
      is associated with glomeruloid microvascular proliferation, an aggressive
      angiogenic phenotype, in malignant melanoma.
AB  - Glomeruloid microvascular proliferations (GMPs), which are focal proliferative
      buddings of endothelial cells resembling a renal glomerulus, can be induced
      experimentally by adenoviral transfer of VEGF-A(165). We recently found that GMPs
      were present in 13-23% of various human tumours (melanoma, breast-, endometrial-
      and prostate cancer), and this vascular signature was significantly associated
      with an impaired prognosis. In the present study, a series of 202 vertical growth
      phase melanomas were examined for the expression of various angiogenic factors
      and their receptors. Presence of GMP was associated with increased expression in
      tumour endothelium of the VEGF-A receptors KDR, FLT-1 and neuropilin-1, as well
      as VEGF-D protein. Thrombospondin-1 staining in the tumour stroma showed the same
      relationship. Endothelial cell expression of VEGF-A was increased in GMP
      endothelium when compared with other intra-tumoural vessels. In contrast, GMP
      expression of bFGF was decreased. Our findings suggest an important role of VEGF
      A and its receptors in GMP formation in human cutaneous melanoma.

PMID- 15166499
TI  - Norepinephrine upregulates vascular endothelial growth factor in rat cardiac
      myocytes by a paracrine mechanism.
AB  - Norepinephrine has growth-promoting effects in cardiac myocytes. The present
      study in cultured neonatal rat cardiac myocytes tested the hypothesis that
      norepinephrine also stimulates expression of vascular endothelial growth factor
      (VEGF), an important angiogenic factor. As assessed by polymerase chain reaction
      cardiac myocytes and non-myocytes expressed all three isoforms of rat VEGF, with
      the short isoform (VEGF 121 ) preferentially expressed in non-myocytes. When
      cardiac myocytes were stimulated with 1 micro M norepinephrine for 24 h in the
      presence or absence of the specific alpha - and beta -adrenoceptor antagonists
      prazosin and propranolol, respectively, VEGF mRNA levels and splice variant
      pattern did not change, whereas atrial natriuretic peptide mRNA levels increased
      3 to 4-fold. CoCl(2) increased VEGF mRNA levels in cardiac myocytes five-fold.
      When cardiac myocytes were cultured with conditioned medium from non-myocytes
      that had been stimulated with norepinephrine for 24 h VEGF mRNA increased 2-fold.
      The increase was blocked by antibodies neutralizing TGF beta. These data suggest
      that norepinephrine stimulates myocardial angiogenesis by a paracrine mechanism
      that involves cardiac non-myocytes and TGF beta.

PMID- 15166500
TI  - The role of the fibrinolytic system in corneal angiogenesis.
AB  - The plasminogen activation system has been implicated in angiogenesis and
      angiogenesis-dependent diseases such as cancer, atherosclerosis and ocular
      diseases. The identification and development of inhibitors of angiogenesis offer
      new possibilities for the treatment of these diseases. To clarify the role of
      proteins involved in the regulation of fibrinolysis during corneal angiogenesis,
      we have studied corneal vessel formation in mice deficient for urokinase-type
      plasminogen activator (uPA), tissue-type plasminogen activator (tPA),
      plasminogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable
      fibrinolysis inhibitor (TAFI). Our results corroborate earlier findings that
      angiogenesis in the mouse cornea is dependent on PAI-1 and plasminogen. The
      absence of tPA, uPA or TAFI did not affect the formation of new vessels in the
      cornea.

PMID- 15166501
TI  - Angiogenin distribution in human term placenta, and expression by cultured
      trophoblastic cells.
AB  - Human angiogenin is a 14-kDa secreted protein with angiogenic and ribonucleolytic
      activities. Angiogenin is associated with tumour development but is also present
      in normal biological fluids and tissues. To further address the physiological
      role of angiogenin, we studied its expression in situ and in vitro, using the
      human term placenta as a model of physiological angiogenesis. Angiogenin was
      immunodetected by light and transmission electron microscopy, and its cellular
      distribution was established by double immunolabelling with cell markers
      including von Willebrand factor, platelet/endothelial cell adhesion molecule-1
      (PECAM-1), CD34, Tie-2, vascular endothelial cadherin (VE-cadherin), vascular
      endothelial growth factor receptor-2 (VEGF-R2), erythropoeitin receptor (Epo-R),
      alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Angiogenin
      immunoreactivity was detected in villous and extravillous trophoblasts, the
      trophoblast basement membrane, the endothelial basal lamina, foetal blood
      vessels, foetal and maternal red blood cells, and amnionic cells. Its expression
      was confirmed by in situ hybridisation with a digoxygenin-labelled cDNA probe and
      reverse transcriptase-polymerase chain reaction amplification. Villous
      cytotrophoblasts, isolated and differentiated in vitro into a functional
      syncytiotrophoblast, expressed and secreted angiogenin. Given its known
      biological activities in vitro and its observed pattern of expression, these data
      suggest that, in human placenta, angiogenin has a role not only in angiogenesis
      but also in vascular and tissue homeostasis, maternal immune tolerance of the
      foetus, and host defences.

PMID- 15166504
TI  - Differentiation of hidroacanthoma simplex from clonal seborrheic keratosis--an
      immunohistochemical study.
AB  - Hidroacanthoma simplex (HS) is an uncommon poroid neoplasm confined within the
      epidermis. The clinical features of HS are not distinctive and
      histopathologically HS may be confused with clonal seborrheic keratosis (CSK) if
      cystic or ductal structure is not present. The purpose of our study was to
      differentiate HS from CSK by the immunohistochemical expressions of various
      cytokeratins, CEA, CD1a, and S-100 protein, as well as by the degrees of
      deposition of melanins and glycogen. Four cases of HS and seven cases of CSK were
      included in the research. In contrast with CSK, HS showed a very low density of
      Langerhans cells (19.9 +/- 7.7 versus 3.1 +/- 1.0 CD1a (+) cells/mm, P = 0.027)
      and sparse melanin deposition in the nests. However, HS could not be set apart
      from CSK by the expressions of cytokeratins. The nests of both HS and CSK showed
      very similar patterns of cytokeratin expression and seemed to be mainly composed
      of basaloid cells with focal differentiation toward epidermal suprabasal cells.

PMID- 15166503
TI  - Sporadic sclerotic fibroma of the oral soft tissues.
AB  - Sclerotic fibroma (SF) is an uncommon, benign fibrous neoplasm that may present
      either as a sporadic, small, solitary cutaneous mass, in otherwise healthy
      individuals, or as solitary or multiple, discrete skin nodules in patients with
      Cowden syndrome. Oral SF has been reported in patients with Cowden syndrome;
      however we now report the first documented series of sporadic SF originating
      within the oral mucosa. We describe 5 cases of SF arising in 3 women and 2 men
      with an age range of 43 to 66 years. The buccal mucosa was the site of
      involvement in 4 patients and the lower lip in 1 patient. Microscopically, each
      of the tumors was characterized by an unencapsulated, well-circumscribed,
      hypocellular submucosal nodule that was sharply demarcated from the surrounding
      tissues. The neoplasms were primarily composed of thick collagen bundles that
      were occasionally arranged in a storiform pattern. Prominent clefts separated
      many of the collagen bundles. In all cases, spindle and stellate-shaped cells
      containing fusiform or stellate-shaped nuclei and inconspicuous nucleoli were
      found scattered throughout the lesion. Occasional stellate-shaped, multinucleated
      cells were also seen. Many of the cells also exhibited long dendritic cytoplasmic
      processes. The tumor cells strongly expressed CD34 and vimentin, and occasionally
      factor XIIIa, but were negative for markers of myofibroblastic, neural or
      melanocytic differentiation. These findings confirm that oral SF represents a
      unique entity and should be differentiated from more commonly occurring benign
      fibrous lesions of the oral soft tissues.

PMID- 15166505
TI  - Epithelial remnants of isthmus-catagen cysts.
AB  - The histopathologic diagnosis of isthmus-catagen cysts is typically rendered with
      ease at scanning magnification. Episodically, diagnostic problems may arise when
      the outermost epithelial portion of the cyst wall separates from the remainder of
      the cyst. If a histopathologist is unaware of this phenomenon, the findings may
      be misinterpreted.

PMID- 15166502
TI  - Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and
      hyperplasias.
AB  - The dysregulation of apoptosis occurs in many cutaneous disease states. Several
      apoptosis inhibitors have been shown elevated in neoplasms and in some
      inflammatory conditions, but their relation to proliferative and apoptotic states
      has not been defined. We examined the expression of the apoptosis inhibitor
      survivin in a panel of keratinocytic neoplasms and hyperproliferative skin
      lesions using both immunohistochemistry and a newly developed in situ
      hybridization technique. Proliferation and apoptotic indices were also assessed
      by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL,
      respectively. We found the highest rate of proliferation in verrucae and
      psoriasis followed by actinic keratosis, squamous and basal cell carcinoma,
      lichen simplex chronicus, and seborrheic keratosis; all were significantly (P <
      0.05) higher than normal skin. Apoptotic rate was increased in squamous (P =
      0.05) and basal cell carcinoma (P = 0.03), but not significantly different from
      normal skin in the other lesions tested. Survivin expression was seen in most
      neoplasms and hyperproliferative lesions, but not normal skin. Survivin
      expression was often restricted to the upper third of the epidermis in psoriasis
      and lichen simplex chronicus, whereas all the other lesions stained diffusely.
      Survivin expression appears to be a consistent feature of keratinocytic neoplasms
      and hyperproliferative lesions and may contribute to the formation of epidermal
      hyperplasia seen in all of these disease states.

PMID- 15166507
TI  - Histopathology of hypotrichosis with juvenile macular dystrophy.
AB  - Hypotrichosis with juvenile macular dystrophy (HJMD) (MIM 601553) is a rare
      disorder characterized by the paucity of hair and progressive macular
      degeneration leading to blindness. We have recently shown that mutations in the
      CDH3 gene encoding P-cadherin are the proximal cause of HJMD. The present study
      was performed to establish the histopathology of this disorder. 4 mm punch scalp
      biopsies from 6 HJMD patients aged 9 to 21 years were studied. All patients had a
      homozygous missense mutation resulting in a single amino acid substitution at
      position 503 of P-cadherin amino acid sequence (R503H). The total number of hair
      follicles varied between 6 and 14 per histologic section. More catagen-telogen
      hair follicles were observed in five cases, and an increased ratio of vellus hair
      follicles to terminal hair follicles was observed in two cases. There were no
      signs of inflammation or scarring. Thus, the most frequent histologic abnormality
      in HJMD resembles chronic telogen effluvium. This suggests that absence of
      functional P-cadherin interferes with normal hair cycle.

PMID- 15166506
TI  - Melanocytes express 3G5 surface antigen.
AB  - The 3G5-reactive ganglioside antigen (3G5 antigen) is expressed on the surface of
      various cell types including pericytes, pancreatic islet cells, thyroid
      follicular cells, and cells of the pituitary and the adrenal medulla. Expression
      on melanocytes has not yet been reported. We examined 148 5-microm cryosections
      of 12 normal skin samples and 45 skin tumors (21 melanocytic nevi, 8 malignant
      melanoma primaries, 4 metastases of malignant melanoma, 3 basal cell carcinomas,
      and 9 pigmented seborrheic keratoses) by triple fluorescence technique with the
      monoclonal antibody 3G5, DNA fluorochrome, and the anti-melanocytic antibody A103
      (Anti-Melan-A). In normal skin, 3G5 reactivity was detected in epidermal
      melanocytes of 4 of 12 cases with 14.8 +/- 24.1% positive melanocytes; 20 of 21
      nevi (72.2 +/- 29.1% positive nevus cells, mean +/- SD), 8 of 8 primary melanomas
      (83.9 +/- 12.3% positive melanoma cells), and 4 of 4 melanoma metastases (82.5 +/
      6.5% positive melanoma cells) expressed the 3G5 antigen. All tumor cells of
      investigated basal cell carcinoma or seborrheic keratosis were 3G5 negative. This
      is the first report of 3G5 antigen expression in melanocytes. The data
      demonstrate high expression of this ganglioside in the aggregated melanocytes of
      malignant or benign tumors but low or absent expression in singular melanocytes
      (normal epidermis, seborrheic keratoses) reflecting a different biologic state.

PMID- 15166508
TI  - Subacute radiation dermatitis.

PMID- 15166509
TI  - Radiation recall dermatitis, panniculitis, and myositis following
      cyclophosphamide therapy: histopathologic findings of a patient affected by
      multiple myeloma.
AB  - Radiation recall dermatitis is one of the skin sequelae that may affect oncology
      patients. It occurs in a previously irradiated field, when subsequent
      chemotherapy is given. The eruption may be elicited by chemotherapy, even several
      months after radiotherapy. Its mechanism is poorly understood, and the
      histopathologic findings have received, to date, only sketchy descriptions. A 55
      year-old male affected by multiple myeloma received radiation therapy both on his
      left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide
      administration, he developed 2 well defined square-shaped, infiltrated
      erythematoviolaceous plaques in the prior irradiated fields. Histopathologic
      findings revealed a diffusely fibrosclerosing process, involving deep dermis,
      hypodermis, as well as the underlying muscle, while sparing the epidermis and
      superficial-mid dermis. Histopathology was indistinguishable from deep radio
      dermatitis, panniculitis, and myositis. This is the first case providing clear
      evidence of the causative role of cyclophosphamide in inducing a cutaneous and
      subcutaneous radiation recall reaction.

PMID- 15166510
TI  - Muir-Torre syndrome: role of the dermatopathologist in diagnosis.
AB  - Muir-Torre syndrome (MTS) is an autosomal dominantly inherited disorder
      characterized by sebaceous lesions and visceral malignancies. The defect is
      thought to be the result of a mutation in mismatch repair genes and associated
      with microsatellite instability. Two cases whose diagnoses were suggested first
      by the dermatopathologist are discussed. The first is a 47-year-old white man who
      over the past 6 years developed multiple sebaceous lesions. Due to the number of
      sebaceous lesions and their morphology, the possible diagnosis of MTS was
      suggested by the dermatopathologist. Subsequently, a lesion in the right colon
      was found during colonoscopy that proved to be a poorly differentiated cecal
      adenocarcinoma. A pedigree analysis revealed other family members afflicted with
      multiple malignancies. Genetic testing of the colonic adenocarcinoma showed
      microsatellite instability. The second patient is a 50-year-old white man who
      underwent biopsy of a skin lesion that showed features of both a sebaceous
      hyperplasia and sebaceous adenoma. Because of the mixed, unusual features of the
      lesion, the dermatopathologist suggested the diagnosis of MTS. It was later
      confirmed that the patient had a history of malignancies of the colon and kidney
      as well as a family history significant for multiple malignant neoplasms. These
      cases demonstrate the important role of the dermatopathologist in alerting the
      clinician to the possibility of Muir-Torre syndrome when the diagnosis of a
      sebaceous neoplasm is made, especially when unusual histologic features are
      observed.

PMID- 15166511
TI  - Angiomyxolipoma (vascular myxolipoma) of subcutaneous tissue.
AB  - Three cases of angiomyxolipoma (vascular myxolipoma) have been published to date.
      We report an angiomyxolipoma located in the subcutaneous tissue of the scalp.
      Histologically, it consisted of an admixture of paucicellular myxoid areas and
      mature fat tissue, both containing numerous dilated blood vessels with hyalinized
      thin walls. The cells in the myxoid areas expressed CD34. This lesion requires
      differential diagnosis with other benign fat tissue tumors, especially myxoid
      spindle cell lipoma, superficial angiomyxoma, myxoid liposarcoma, and low-grade
      myxofibrosarcoma.

PMID- 15166512
TI  - Disseminated cutaneous B-cell lymphoma mimicking pseudolymphoma over a period of
      six years.
AB  - We describe a patient with a disseminated nodular cutaneous B-cell lymphoma,
      whose diagnosis was finally made after a long series of biopsies in different
      institutions in Europe and the United States. The differential diagnosis between
      lymphoma and pseudolymphoma was the recurrent problem throughout the patient's
      history because histologic and immunophenotypic criteria alone were not
      sufficient for differentiation. Molecular biology inconsistently detected clonal
      immunoglobulin rearrangements, which proves that careful clinicopathologic
      correlation remains mandatory. In contrast to a claimed "high-grade" malignant
      histology, this lymphoma responded with remission to PUVA therapy combined with
      intralesional corticosteroids, which is uncommon in the management of cutaneous B
      lymphomas.

PMID- 15166513
TI  - A case of intraepidermal Merkel cell carcinoma within squamous cell carcinoma in
      situ: Merkel cell carcinoma in-situ?
AB  - We report a case of a 79-year-old Caucasian male who presented with a wrist
      lesion of combined intraepidermal Merkel cell carcinoma and squamous cell
      carcinoma in-situ. The two tumors were tightly admixed and distinct, and both
      were without any dermal or invasive components. No features of transition between
      the two tumors were seen. We suggest the term Merkel cell carcinoma in situ for
      tumors that demonstrate exclusive intraepidermal proliferation of neuroendocrine
      cells.

PMID- 15166514
TI  - Atypical CD30+ cutaneous lymphoid proliferation in a patient with tuberculosis
      infection.
AB  - We describe the case of a 65-year-old woman affected by a diffuse lymphadenopathy
      consistent with tuberculous infection who developed a papular eruption on the
      head and neck region. Histopathologic examination of one papule showed an
      atypical CD30+ lymphoid infiltrate, which initially was cause of concern for the
      pathologists but was eventually regarded as reactive in nature. The case reported
      herein enlarges the spectrum of inflammatory infiltrates in which atypical CD30+
      cells may be found. Since the reactive atypical CD30+ cells are morphologically
      similar to those cells observed in CD30+ lymphoproliferative disorders, including
      lymphomatoid papulosis, complete clinical history and laboratory findings are
      necessary to make the final and correct diagnosis. Although the pathogenetic
      relevance of the presence of CD30+ cells within the cutaneous infiltrate of
      patients with systemic tuberculosis remains to be determined, our findings
      support the hypothesis that the cytokine profile associated with tuberculosis may
      not be strictly TH1-like, and that a TH1-like to TH2-like switch may also occur.

PMID- 15166515
TI  - Benign fibrous histiocytoma with indeterminate cells and eosinophils: collision,
      differentiation, or involution?
AB  - This report describes the clinicopathologic, immunohistochemical, and
      ultrastructural features of a benign fibrous histiocytoma of 3 years' duration
      situated on the posterior right arm of a 17-year-old woman. To our knowledge,
      this is the first published description of an association between the histologic
      features of benign fibrous histiocytoma with proliferating dermal dendrocytes and
      solid clusters of indeterminate cells and inflammatory infiltrate containing
      numerous eosinophils. Cell type identification was confirmed by
      immunohistochemical demonstration of positivity of indeterminate cells for CD1a
      and S-100 protein, by absence of Birbeck granules in electron microscopy study,
      and by positivity of fibroblast-like cells for factor XIIIa and negativity for
      CD34. Mitosis or cytologically atypical cells were absent. The MIB1-measured
      proliferative index of the tumor cells was less than 5% in spindle cells and
      approximately 15% in indeterminate cells. Possible pathogenic pathways are
      discussed that could account for divergent differentiation or a combination of
      neoplasms of different lineages.

PMID- 15166516
TI  - Immunofluorescent and FISH analysis of skin biopsies.
AB  - Cutaneous biopsies are traditionally studied for the expression of cellular
      markers by immunoenzymatic techniques. However, immunofluorescent analysis is a
      valuable, and largely overlooked, ancillary technique that can resolve questions
      arising from conventional immunostaining, since it allows pairs of antigens to be
      simultaneously visualized. Furthermore, a novel technique, based on a combination
      of immunoperoxidase and immunofluorescent staining, allows three markers to be
      demonstrated together. Fluorescent microscopy also allows skin biopsies from
      lymphoma cases to be analyzed for chromosomal abnormalities by the fluorescent in
      situ hybridization (FISH) technique, which is now applicable to routine biopsy
      samples. In this review, we describe the technical aspects of immunofluorescent
      and FISH analysis of routine cutaneous biopsy samples.

PMID- 15166517
TI  - Nasal tumor in a Peruvian man.

PMID- 15166518
TI  - Histopathological pictures of the initial changes of the hair bulbs in alopecia
      areata.
AB  - A biopsy of the seemingly normal scalp of a patient who had just begun to develop
      alopecia areata showed distinctive changes in bulbar morphology, in addition to
      peribulbar lymphocytic infiltrates. One of these changes was a loss of structural
      integrity of the centrally located supramatrical upper bulbar region. The other
      was the shrinkage of hair bulbs in the direction of club shape. Uninvolved intact
      anagen follicles were also present among these involved follicles.

PMID- 15166520
TI  - What is it? Unusual interstitial fibrohistiocytic tumor or other.
AB  - Fibrohistiocytic lesions are capable of presenting in a variety of histologic
      guises. We have recently encountered two lesions that similarly showed a hitherto
      described proliferation of atypical spindled and stellate cells with a
      distinctive deep dermal and interstitial distribution. The pathogenic
      significance and nosologic status of this neoplasm is unknown.

PMID- 15166521
TI  - Recurrent malignant melanoma 51 years after the diagnosis of ocular melanoma.

PMID- 15166522
TI  - Margin call.

PMID- 15166523
TI  - Retraction. Clinical course of cardiomyopathy in HIV-infected patients with or
      without encephalopathy related to the myocardial expression of tumour necrosis
      factor-alpha and nitric oxide synthase.

PMID- 15166524
TI  - HIV-associated nephropathy.

PMID- 15166525
TI  - Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows
      latent viral expression.
AB  - BACKGROUND: Histone deacetylase (HDAC), a host mediator of gene repression,
      inhibits HIV gene expression and virus production and may contribute to
      quiescence of HIV within resting CD4 T cells. OBJECTIVES: To test the ability of
      valproic acid (VPA), an inhibitor of HDAC in clinical use, to induce expression
      of HIV from resting CD4 T cells. METHODS: Chromatin immunoprecipitation measured
      the capability of VPA to deacetylate the HIV promoter, a remodeling of chromatin
      linked to gene expression. The effect of VPA on resting CD4 T cell phenotype was
      measured by flow cytometric analysis, and its effect on de novo HIV infection of
      peripheral blood mononuclear cells was measured ex vivo. Outgrowth of HIV from
      resting CD4 T cells of aviremic, HIV-infected donors treated with highly active
      antiretroviral therapy was compared in limiting-dilution cultures after mitogen
      stimulation or exposure to VPA. RESULTS: VPA induced acetylation at the
      integrated HIV proviral promoter, but CD4 cells exposed to VPA did not become
      activated or more permissive for de novo HIV infection. VPA induced outgrowth of
      HIV from the resting CD4 cells of aviremic patients at concentrations achievable
      in vivo as frequently as did mitogen stimulation. CONCLUSIONS: With advances in
      antiretroviral therapy, HIV infection might be cleared by intensive time-limited
      treatment coupled with practical strategies that disrupt latency without
      enhancing new infection. HDAC inhibitors are capable of inducing expression of
      quiescent provirus, without fully activating cells or enhancing de novo
      infection, and may be useful in future clinical protocols that seek to eradicate
      HIV infection.

PMID- 15166526
TI  - Differences in disease progression in a cohort of long-term non-progressors after
      more than 16 years of HIV-1 infection.
AB  - BACKGROUND: It is unclear whether resistance to immunologic damage in long-term
      non-progressors (LTNP) will last indefinitely or whether it merely represents the
      extreme of a Gaussian distribution, and therefore progression will occur
      eventually. PATIENTS AND METHODS: A cohort of 19 LTNP was established in 1997.
      Plasma viraemia and CD4 cell counts were measured two to three times each year
      until 2003. Analyses of nef and vpr viral genes, CCR5 genotypes, co-receptor
      tropism, viral replication capacity, and immunological parameters were performed.
      RESULTS: Twelve subjects (non-progressors, NP) showed stable CD4 cell counts over
      the 6-year follow-up, while seven (slow progressors, SP) showed a trend towards
      progressive CD4 cell depletion; however, only three SP experienced significant
      CD4 cell count declines. All SP had detectable plasma HIV-RNA (median 1118
      copies/ml). In contrast, five of 12 NP had always undetectable viraemia. Only one
      patient showed a deletion in nef. The vpr R77Q change was recognized in seven
      patients. All patients were infected with R5 viruses. The virus replicative
      capacity was reduced in all tested individuals (range 5-93%). None of the
      patients was homozygous for the delta-32 CCR5 genotype, which was found in
      heterozygosis in three. CD8 T-cell activation was low in all but three
      individuals, all of whom had detectable viraemia and showed progressive CD4 cell
      depletion. Cytotoxic T lymphocyte responses were similar to those found in a
      control group of HIV progressors. CONCLUSIONS: A substantial proportion of LTNP
      show low-level virus replication and progressive loss of CD4 T cells over time.
      Progressive immunologic damage seems to be directly associated with some degree
      of virus replication and T-cell activation.

PMID- 15166527
TI  - Correlates of resistance to HIV-1 infection in homosexual men with high-risk
      sexual behaviour.
AB  - OBJECTIVE: To investigate possible correlates of HIV resistance in participants
      from the Amsterdam Cohort of Homosexual men who have remained HIV seronegative
      despite high-risk sexual behaviour. DESIGN/METHODS: We studied in vitro HIV-1
      susceptibility and adaptive and innate immunity in 29 high-risk seronegative
      (HRSN) and 15 HIV-negative pre-seroconversion (pre-SC) homosexual men from the
      same Amsterdam Cohort Study (ACS) who seroconverted to HIV-1 positive during
      active follow-up. Host genetics were compared between HRSN and HIV-positive ACS
      participants. RESULTS: We found lower in vitro susceptibility for a CCR5-using
      (R5) HIV-1 variant, higher RANTES production levels, but no difference in
      coreceptor expression in HRSN as compared with pre-SC controls. Reduced R5 in
      vitro susceptibility of two HRSN tested was restored to normal levels by addition
      of antibodies against beta-chemokines. A higher proportion of HRSN carried the
      SDF-1 3'A variant and HLA-A*11, A*31 and Cw*15 alleles. ELIspot analysis with HIV
      1 peptide stimulation revealed low frequencies of HIV-1-specific CD8 interferon
      gamma producing cytotoxic T cells in both HRSN and pre-SC controls. CONCLUSIONS:
      Low in vitro R5 susceptibility of cells from the HRSN men was due to beta
      chemokine mediated inhibition of virus replication. The presence of HIV-1
      specific cytotoxic T cells in both HRSN and pre-SC participants may signify
      exposure to the virus rather than protection from infection. Host genetic
      characteristics and other factors affecting innate immunity may contribute to
      differential resistance to HIV-1 infection among exposed seronegative
      individuals.

PMID- 15166528
TI  - Chronic HIV-2 infection protects against total CD4+ cell depletion and rapid
      disease progression induced by SHIV89.6p challenge.
AB  - OBJECTIVE: To better understand HIV-1 sexual transmission risk, we have studied
      the susceptibility of HIV-2-exposed, uninfected (EU) female pig-tailed macaques
      to intravaginal (IVAG) re-challenge with the homologous HIV-2 strain, followed by
      heterologous SHIV89.6p. METHODS: Nine female macaques, previously protected by a
      post-exposure prophylaxis (PEP) regimen, along with one mock-treated EU animal,
      were re-exposed to HIV-2 by the IVAG route approximately 1.5 years later. A
      single follow-up challenge was performed approximately 1 year later with
      SHIV89.6p to assess susceptibility of chronic HIV-2-infected animals to further
      re-infection and pathogenic effects with a heterologous virus, somewhat mimicking
      HIV-1. RESULTS: Eight of ten macaques (80%) became infected systemically with HIV
      2, and plasma or cervicovaginal vRNA levels did not appreciably differ from prior
      historic non-PEP control macaques. Interestingly, all eight HIV-2-infected
      females were susceptible to SHIV89.6p infection by either intravenous (n = 4) or
      IVAG exposure (n = 4) after one inoculation. Plasma vRNA levels in these groups
      were controlled by week 8 and there were no decrease in CD4+ T cells > 50%. The
      remaining two HIV-2 EU macaques, inoculated intrarectally with SHIV89.6p, were
      unable to control virus replication and succumbed to disease by week 25 or week
      61. CONCLUSIONS: Our findings demonstrate that successful PEP regimens to prevent
      an initial infection do not have any lasting protective effects. The observed
      lack of cross-protection against SHIV89.6p transmission among chronic HIV-2
      infected macaques provides modeling support for limited epidemiologic data
      indicating that human HIV-2 infection does not protect against HIV-1 infection,
      but may serve to alter overt clinical outcome.

PMID- 15166529
TI  - Clinical management of treatment-experienced, HIV-infected patients with the
      fusion inhibitor enfuvirtide: consensus recommendations.
AB  - The introduction of enfuvirtide (FUZEON) represents an important advance in the
      treatment of therapy-experienced patients with HIV-1 infection. However,
      parenteral self-administration, and the advanced disease and antiretroviral
      experience of patients currently most needing enfuvirtide introduce unique usage
      considerations. Enfuvirtide has been shown to provide clinically relevant
      improvements in CD4 cell counts and reductions in HIV viraemia across all
      subgroups of treatment-experienced patients studied, including those taking few
      or no other active drugs. However, optimal outcome results from initiation when
      the CD4 cell count is above 100 x 10(6) cells/l and viraemia below 1 x 10(5)
      copies/ml, as part of a newly constructed third or fourth antiretroviral regimen
      in combination with one or two other antiretrovirals to which the virus remains
      sensitive. Resistance testing should be used where available to guide background
      drug selection. Where insufficient options for an effective background exist,
      enfuvirtide should still be considered and treatment undertaken with the aim of
      achieving an immunological or clinical response, despite the unlikelihood of a
      sustained virological outcome. Similarly, where there is no viable alternative
      treatment, enfuvirtide should be continued following virological failure wherever
      ongoing immunological or clinical benefit is discerned. Injection site reactions
      (ISRs) are common on enfuvirtide and will affect almost all patients. ISRs are
      manageable and seldom activity- or treatment-limiting. Bacterial pneumonia and
      systemic hypersensitivity reactions have also been reported uncommonly. A
      structured series of patient visits with a healthcare professional provides an
      atmosphere of ongoing training and support that may prevent 'injection fatigue',
      maintain adherence and minimise the incidence of ISRs. An initial investment in
      establishing such procedures can be expected to yield significant returns in
      patient confidence and benefit on enfuvirtide.

PMID- 15166530
TI  - The lymphocyte HIV reservoir in patients on long-term HAART is a memory of virus
      evolution.
AB  - OBJECTIVE: To investigate the dynamics of the lymphocyte HIV reservoir in
      patients on prolonged and effective highly active antiretroviral therapy (HAART).
      DESIGN: Nine HAART-treated patients were selected on the basis of long-term
      infection and long-term undetectable plasma viral RNA. Five patients had received
      antiretroviral therapy before HAART. We compared a polymorphic region of the env
      gene (C2V4), and the part of the pol gene encoding the reverse transcriptase in
      pre-HAART plasma and in the reservoir lymphocytes during HAART; the first plasma
      sample taken after structured treatment interruption was also studied in three
      patients. METHODS: Both regions of interest were amplified from plasma HIV RNA
      and cellular proviral DNA, then cloned, sequenced and subjected to phylogenetic
      analysis. RESULTS: Diversity of the lymphocyte reservoir was found in six of nine
      patients. Archiving of pre-HAART plasma clones was observed in six of nine
      patients. 'Wild-type' and zidovudine-resistant strains co-existed in reservoir T
      cells of two pre-HAART treated patients. In three patients, no resistant virus
      was found in the T-cell reservoir despite the detection of resistant virus in pre
      HAART plasmas. However, virus archiving was documented in two of these three
      patients on the basis of C2V4 analysis. Latently infected T cells only partly
      accounted for the plasma viral load rebound after structured treatment
      interruption. CONCLUSIONS: The HIV lymphocyte reservoir is dynamic. Its diversity
      results mainly from successive archiving of circulating plasma viruses during the
      course of HIV infection. Archiving of resistant virus must be taken into account
      in therapeutic decisions.

PMID- 15166531
TI  - Initiating highly active antiretroviral therapy in sub-Saharan Africa: an
      assessment of the revised World Health Organization scaling-up guidelines.
AB  - OBJECTIVES: To assess the utility of the 2003 revised World Health Organization
      (WHO) criteria [initiating highly active antiretroviral therapy (HAART) in stage
      IV, in stage III plus CD4 cell count < 350 x 10(6) cells/l, or in stage I or II
      plus CD4 cell count < 200 x 10 cells/l] relative to other scenarios of HAART
      initiation. METHODS: Progression to AIDS and death in 292 patients taking HAART
      and 974 not taking HAART in a South African institution in 1992-2001, stratifying
      patients by baseline CD4 cell count and WHO stage. RESULTS: HAART was associated
      with decreased AIDS [adjusted rate ratio [ARR], 0.16; 95% confidence interval
      (CI), 0.08-0.31) and death (ARR, 0.10; 95% CI, 0.06-0.18). Benefit of HAART was
      significant across all WHO stages plus CD4 cell counts. The greatest number of
      deaths averted was in stages IV [74.0/100 patient-years (PY); 95% CI, 50.2-84.5)
      and III (32.8/100 PY; 95% CI, 22.4-40.9). AIDS cases averted in stage III
      (22.0/100 PY; 95% CI, 6.1-26.9) were higher than in stage I and II with CD4 cell
      count < 200 x 10(6) cells/l (8.9/100 PY 95% CI, 5.6-13.3). Treatment initiation
      for symptomatic disease resulted in greater benefits than using any CD4 cell
      thresholds. Application of WHO criteria increased the treatment-eligible
      proportion from 44.5% to 56.7% (P < 0.05) but did not prevent more death (P >
      0.05) than treating symptomatic disease. CONCLUSION: Implementation of the
      revised WHO guidelines in sub-Saharan Africa may result in a significantly
      increased number of individuals eligible for treatment but would not be as
      effective a strategy for preventing death as treating symptomatic disease.

PMID- 15166532
TI  - Impact of viral hepatitis co-infection on response to antiretroviral therapy and
      HIV disease progression in the HIV-NAT cohort.
AB  - OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease
      outcomes following commencement of combination antiretroviral therapy in a
      developing country setting. METHODS: HIV RNA suppression, CD4 cell count
      recovery, and HIV disease progression were examined within a cohort of Thai HIV
      infected patients enrolled in eight HIV-NAT randomized controlled trials of
      antiretroviral therapy (n = 692). Hepatitis B virus (HBV) and hepatitis C virus
      (HCV) testing was performed on stored serum. RESULTS: Mean age was 32.3 years,
      52% were male, 11% had CDC category C HIV disease at baseline, and 22% had
      received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV co
      infection was 8.7, 7.2 and 0.4%, respectively. Median HIV RNA reductions (log10
      copies/ml) were approximately 1.5 for HIV, HIV-HBV, HIV-HCV subgroups from week 4
      up to week 48. Mean increases in CD4 cell count were significantly lower among
      HIV-HBV and HIV-HCV subgroups at week 4 (HIV, 62 x 10(6) cells/l; HIV-HBV, 29 x
      10(6) cells/l; HIV-HCV, 33 x 10(6) cells/l), however, by week 48 CD4 cell
      increases were similar (HIV, 115 x 10(6) cells/l; HIV-HBV, 113 x 10(6) cells/l;
      HIV-HCV, 97 x 10(6) cells/l). Cox regression analyses showed that HIV-HBV or HIV
      HCV co-infection were not associated with a CD4 cell count increase of 100 x
      10(6) cells/l over 48 weeks. Estimated progression to AIDS event or death at week
      48 was 3.3% (95% confidence interval, 2.0-5.1%) for HIV, 6.7% (2.5-14.6%) for HIV
      HBV, and 8.0% (2.2-20.5%) for HIV-HCV subgroups (P > 0.05). CONCLUSIONS: An early
      delayed CD4 count recovery among HIV/viral hepatitis co-infected patients was not
      sustained, and was not associated with increased HIV disease progression.

PMID- 15166533
TI  - Effect of brief safer-sex counseling by medical providers to HIV-1 seropositive
      patients: a multi-clinic assessment.
AB  - OBJECTIVE: To test the efficacy of brief, safer-sex counseling by medical
      providers of HIV-positive patients during medical visits. SETTING: Six HIV
      clinics in California. DESIGN: Clinics were randomized to intervention arms
      evaluated with cohorts of randomly selected patients measured before and after
      the intervention. PARTICIPANTS: Five-hundred and eighty-five HIV-positive
      persons, sexually active prior to enrollment. INTERVENTIONS: Prevention
      counseling from medical providers supplemented with written information. Two
      clinics used a gain-framed approach (positive consequences of safer-sex), two
      used a loss-frame approach (negative consequences of unsafe sex), and two were
      attention-control clinics (medication adherence). Interventions were given to all
      patients who attended the clinics. OUTCOME MEASURE: Self-reported unprotected
      anal or vaginal intercourse (UAV). RESULTS: Among participants who had two or
      more sex partners at baseline, UAV was reduced 38% (P < 0.001) among those who
      received the loss-frame intervention. UAV at follow-up was significantly lower in
      the loss-frame arm [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.19
      0.91; P = 0.03] compared with the control arm. Using generalized estimating
      equations (GEE) to adjust for clustering did not change the conclusions (OR,
      0.34; 95% CI, 0.24-0.49; P = 0.0001). Similar results were obtained in
      participants with casual partners at baseline. No effects were seen in
      participants with only one partner or only a main partner at baseline. No
      significant changes were seen in the gain-frame arm. CONCLUSIONS: Brief provider
      counseling emphasizing the negative consequences of unsafe sex can reduce HIV
      transmission behaviors in HIV-positive patients presenting with risky behavioral
      profiles.

PMID- 15166534
TI  - Polymorphism of Fc receptor IIa for IgG in infants is associated with
      susceptibility to perinatal HIV-1 infection.
AB  - OBJECTIVE: To evaluate the effect of polymorphism of the Fc gamma receptor IIa,
      which is associated with differential human IgG subclass binding, on perinatal
      HIV-1 transmission. METHODS: Fc gamma RIIa genotype was tested in 448 HIV
      seropositive mothers and their infants from a cohort study designed to assess the
      effect of placental malaria on HIV vertical transmission conducted from 1996 to
      2001 in western Kenya. Fc gamma RIIa polymorphism was analyzed for associations
      with susceptibility to perinatal HIV infection and all-cause child mortality in
      HIV-positive children. RESULTS: Overall, 20% of infants were perinatally infected
      with HIV. There was no statistically significant association between maternal
      genotype and perinatal HIV-1 transmission. However, frequency of the infant Fc
      gamma RIIa His/His131 genotype was higher in HIV-positive compared with HIV
      negative infants (35% and 21%, respectively), whereas the distribution was
      reversed (15% and 28%, respectively) for infants with the Fc gamma RIIa
      Arg/Arg131 genotype. Multivariate logistic regression controlling for maternal
      and infant confounding factors demonstrated that the odds of perinatal HIV
      infection in infants with the Fc gamma RIIa His/His131 versus Fc gamma RIIa
      His/Arg131 genotypes were significantly higher (adjusted odds ratio, 2.22; 95%
      confidence interval, 1.23-4.02; P = 0.009). There was no evidence for an
      association between HIV-positive child all-cause mortality and Fc gamma RIIa
      genotype. CONCLUSIONS: This study provides the first evidence that the infant Fc
      gamma RIIa His/His131 genotype is associated with susceptibility to perinatal HIV
      1 transmission and further suggests that there is a dose-response relationship
      for the effect of the Fc gamma RIIa His131 gene on transmission.

PMID- 15166535
TI  - Long-term effects of condom promotion programmes for vaginal and oral sex on
      sexually transmitted infections among sex workers in Singapore.
AB  - OBJECTIVES: To evaluate the long-term impact of condom promotion programmes for
      vaginal and oral sex among female brothel-based sex workers in Singapore. DESIGN:
      A pre-test/post-test comparison group followed by a time series design was used
      to compare trends in condom use for vaginal sex and cervical gonorrhoea incidence
      from 1990 to 2002 across cross-sectional samples of sex workers before and after
      programme implementation in 1995. The subsequent condom promotion programme for
      oral sex was evaluated using the interrupted time series with a retrospective pre
      test to post-test matched control group design. METHODS: Sex workers completed a
      questionnaire before and 6 months after participation in educational sessions.
      Cervical and pharyngeal swabs were taken monthly for cultures for Neisseria
      gonorrhoeae. RESULTS: Consistent condom use for vaginal sex increased
      significantly from < 45.0% before 1995 (pre-intervention period) to 95.1% in
      2002, with a corresponding decline in cervical gonorrhoea incidence from > 30 to
      2/1000 person-months. Adjustment for temporal changes in sociodemographic
      characteristics did not materially alter the trends. Consistent oral condom use
      increased significantly from < 50% before 1996 to 97.2% in 2002, with a
      corresponding decline in pharyngeal gonorrhoea from > 12 to 4.7/1000 person
      months. CONCLUSION: The interventions produced sustained high levels of condom
      use for vaginal and oral sex with corresponding declines in cervical and
      pharyngeal gonorrhoea incidence.

PMID- 15166536
TI  - Drug resistance mutations: yes but where?

PMID- 15166537
TI  - Safety and immunogenicity of a polyvalent peptide C4-V3 HIV vaccine in
      conjunction with IL-12.
AB  - We examined the safety and immunogenicity of a human leukocyte antigen-based HIV
      envelope polyvalent synthetic peptide vaccine, C4-V3, alone and in combination
      with subcutaneous IL-12 in nine HIV-infected patients. Lymphocyte proliferative
      responses increased threefold or more to all four peptides at two consecutive
      post-immunization timepoints for four individuals. Three responders had received
      IL-12, suggesting a possible adjuvant effect of Il-12. Transient mild injection
      site reactions (7.9) and systemic symptoms (3/9) occurred.

PMID- 15166538
TI  - An IL-8 gene promoter polymorphism is associated with the risk of the development
      of AIDS-related Kaposi's sarcoma: a case-control study.
AB  - In a case-control study, we studied the effect of a single nucleotide
      polymorphism in the IL-8 promoter on the risk of the development of AIDS-related
      Kaposi's sarcoma (KS). KS developed in 46% of individuals with the TT genotype
      and in 66% of AA/AT genotypes (P=0.038). Patients with TT genotype were rarely
      affected with visceral KS (7% versus 36%; P=0.06), which suggests that carriers
      of the TT genotype are protected from (severe) KS development.

PMID- 15166539
TI  - Higher viral load may explain the dominance of CRF02_AG in the molecular
      epidemiology of HIV in Ghana.
AB  - Phylogenetic analysis of Ghanaian plasma samples from 84 asymptomatic candidate
      blood donors and 150 AIDS patients revealed a 63% prevalence of HIV-1 CRF02_AG.
      HIV-1 viral load in both populations was quantified using real-time reverse
      transcriptase-polymerase chain reaction. In asymptomatic candidate blood donors
      infected with CRF02_AG, the viral load was significantly higher than in donors
      infected with other HIV-1 molecular forms. A higher viral load of CRF02-AG is
      compatible with higher infectivity and prevalence.

PMID- 15166540
TI  - 23-Valent pneumococcal polysaccharide vaccine in HIV-infected Ugandan adults: 6
      year follow-up of a clinical trial cohort.
AB  - 23-Valent pneumococcal polysaccharide vaccine was previously reported to be
      ineffective in HIV-infected Ugandan adults. Prolonged follow-up of trial
      participants confirmed persistent excess of all-cause pneumonia in vaccine
      recipients [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.0-2.4], but
      surprisingly a survival advantage favouring vaccination (HR 0.84; CI 0.7-1.0). An
      explanation for the improvement in survival in the face of excess morbid events
      is lacking; a role for vaccine in HIV care in Africa remains unlikely.

PMID- 15166541
TI  - Adenovirus types 5 and 35 seroprevalence in AIDS risk groups supports type 35 as
      a vaccine vector.
AB  - The seroprevalence of adenovirus types 5 (Ad5) and 35 (Ad35) was investigated in
      patients at risk of AIDS. The seroprevalence of Ad5 was higher than Ad35 in HIV
      infected patients from The Netherlands (60% versus 7%) and sub-Saharan Africa
      (90% versus 20%). The seroprevalence was similar among HIV-infected and
      uninfected individuals, and remained constant during progression to AIDS. Ad35 is
      less prone to neutralization than Ad5, encouraging the further development of
      Ad35 for vaccination against HIV.

PMID- 15166542
TI  - Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC
      chemokines.

PMID- 15166543
TI  - Compartmentalization of the immune response in varicella zoster virus immune
      restoration disease causing transverse myelitis.

PMID- 15166544
TI  - Buschke-Loewenstein lesion: another possible manifestation of immune restoration
      inflammatory syndrome?

PMID- 15166545
TI  - Relapsing meningitis caused by persistent cryptococcal antigens and immune
      reconstitution after the initiation of highly active antiretroviral therapy.

PMID- 15166546
TI  - Is switching protease inhibitor-based effective antiretroviral therapy safe in
      patients with AIDS-associated Kaposi's sarcoma?

PMID- 15166547
TI  - Indirect markers to initiate highly active antiretroviral therapy in a rural
      African setting.

PMID- 15166549
TI  - Glucose and heart surgery: neonates are not just small adults.

PMID- 15166551
TI  - Fishing for genes: practical ways to study genetic polymorphisms for pain.

PMID- 15166550
TI  - Rested and refreshed after anesthesia? Overlapping neurobiologic mechanisms of
      sleep and anesthesia.

PMID- 15166552
TI  - Intraoperative hyperglycemia during infant cardiac surgery is not associated with
      adverse neurodevelopmental outcomes at 1, 4, and 8 years.
AB  - BACKGROUND: It is unknown whether intraoperative hyperglycemia in infants is
      associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary
      bypass (LF), deep hypothermic circulatory arrest (CA), or both. METHODS: In a
      database review of a prospective trial of 171 infants undergoing arterial switch
      for D-transposition of the great arteries who were randomly assigned to
      predominantly LF or CA, glucose was measured after induction (T1), 5 min after
      cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after CPB
      resumption (T4), at rewarming to 32 degrees C (T5), 10 min after cardiopulmonary
      bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes included seizures,
      electroencephalographic findings, and neurodevelopmental evaluation at 1, 4, and
      8 yr. RESULTS: Glucose concentrations were affected by support strategy and age
      at surgery. Lower glucose in the entire group at T6-T7 tended to predict
      electroencephalographic seizures (P = 0.06 and P = 0.007) but was not related to
      clinical seizures. Within the predominantly CA group, higher glucose did not
      correlate with worse outcomes. Rather, it was associated with more rapid
      electroencephalographic normalization of "close burst" and "relative continuous"
      activity at all times except T2 (P < or = 0.03), a finding more pronounced in
      infants aged 7 days old or younger. Intraoperative serum glucose concentrations
      were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8 yr.
      CONCLUSIONS: Low glucose after cardiopulmonary bypass tended to relate to
      electroencephalographic seizures and slower electroencephalogram recovery,
      independent of CA duration. High glucose concentrations were not associated with
      worse neurodevelopmental outcomes. Avoiding hypoglycemia may be preferable to
      restricting glucose in infants undergoing heart surgery.

PMID- 15166553
TI  - Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis,
      tolerance of laryngoscopy, bispectral index, and electroencephalographic
      approximate entropy.
AB  - BACKGROUND: The purpose of this investigation was to describe the pharmacodynamic
      interaction between propofol and remifentanil for probability of no response to
      shaking and shouting, probability of no response to laryngoscopy, Bispectral
      Index (BIS), and electroencephalographic approximate entropy (AE). METHODS:
      Twenty healthy volunteers received either propofol or remifentanil alone and then
      concurrently with a fixed concentration of remifentanil or propofol,
      respectively, via a target-controlled infusion. Responses to shaking and shouting
      and to laryngoscopy were assessed multiple times after allowing for plasma effect
      site equilibration. The raw electroencephalogram and BIS were recorded throughout
      the study, and AE was calculated off-line. Response surfaces were fit to the
      clinical response data using logistic regression or hierarchical response models.
      Response surfaces were also estimated for BIS and AE. Surfaces were visualized
      using three-dimensional rotations. Model parameters were estimated with NONMEM.
      RESULTS: Remifentanil alone had no appreciable effect on response to shaking and
      shouting or response to laryngoscopy. Propofol could ablate both responses.
      Modest remifentanil concentrations dramatically reduced the concentrations of
      propofol required to ablate both responses. The hierarchical response surface
      described the data better than empirical logistic regression. BIS and AE are more
      sensitive to propofol than to remifentanil. CONCLUSIONS: Remifentanil alone is
      ineffective at ablating response to stimuli but demonstrates potent synergy with
      propofol. BIS and AE values corresponding to 95% probability of ablating response
      are influenced by the combination of propofol and remifentanil to achieve this
      endpoint, with higher propofol concentrations producing lower values for BIS and
      AE.

PMID- 15166554
TI  - A response surface analysis of propofol-remifentanil pharmacodynamic interaction
      in volunteers.
AB  - BACKGROUND: Characterizing drug interactions using a response surface allows for
      the determination of the interaction over a complete range of clinically relevant
      concentrations. Gathering the data necessary to create this surface is difficult
      to do in a clinical setting and requires the use of volunteer experiments with
      surrogate noxious stimuli to adequately control the process for data collection.
      The pharmacodynamic synergy of opioids and hypnotics was investigated using a
      volunteer study paradigm. METHODS: Twenty-four volunteer subjects (12 male, 12
      female) were studied using computer-controlled infusions of propofol and
      remifentanil to create an increasing staircase drug concentration profile in each
      subject. Three different drug delivery profiles were administered to subjects,
      one with a single agent and two with combinations of propofol and remifentanil.
      At each plateau of the staircase profile, drug effect was assessed using four
      surrogate measures: Observer Assessment of Alertness/Sedation score, tibial
      pressure algometry, electrical tetany, and response to laryngoscopy. Response
      surfaces were developed that mapped the interaction of propofol and remifentanil
      to these surrogate effect measures in all subjects. An interaction parameter was
      used to assess whether these two drugs behave synergistically to blunt response
      to noxious stimuli. RESULTS: The response surfaces showed considerable synergy
      between remifentanil and propofol for blunting response to the noxious stimuli.
      The interaction index, a measure of synergy, was 8.2 and 14.7 for response to
      algometry and tetany, respectively (P < 0.001), and 5.1 and 33.2 for sedation and
      laryngoscopy, respectively (P < 0.001), using the Greco interaction model. The
      surrogate stimuli mapped to clinically relevant concentrations for these agents
      in combination. CONCLUSIONS: The response surface models reveal the tremendous
      synergy between remifentanil and propofol. The surface morphologic features give
      some indication of the relative contribution of sedation and analgesia to
      blunting subject response. Further, the results of this investigation validate
      the volunteer study paradigm and use of surrogate effect measures for its
      clinical relevance.

PMID- 15166555
TI  - Determination of the pharmacodynamic interaction of propofol and remifentanil
      during esophagogastroduodenoscopy in children.
AB  - BACKGROUND: Propofol is commonly used to anesthetize children undergoing
      esophagogastroduodenoscopy. Opioids are often used in combination with propofol
      to provide total intravenous anesthesia. Because both propofol and remifentanil
      are associated with rapid onset and offset, the combination of these two drugs
      may be particularly useful for procedures of short duration, including
      esophagogastroduodenoscopy. The authors previously demonstrated that the median
      effective concentration (C50) of propofol during esophagogastroduodenoscopy in
      children is 3.55 microg/ml. The purpose of this study was to describe the
      pharmacodynamic interaction of remifentanil and propofol when used in combination
      for esophagogastroduodenoscopy in pediatric patients. METHODS: The authors
      studied 32 children aged between 3 and 10 yr who were scheduled to undergo
      esophagogastroduodenoscopy. Propofol was administered via a target-controlled
      infusion system using the STANPUMP software based on a pediatric pharmacokinetic
      model. Remifentanil was administered as a constant rate infusion of 25, 50, and
      100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax
      model was developed to describe the interaction of remifentanil and propofol.
      RESULTS: There was a positive interaction between remifentanil and propofol when
      used in combination. The concentration of propofol alone associated with 50%
      probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was
      decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with
      remifentanil. CONCLUSION: A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces
      the concentration of propofol required for adequate anesthesia for
      esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil
      infusion yields minimal additional decrease in propofol concentration and may
      increase the risk of side effects.

PMID- 15166556
TI  - Evidence for development of capillary leak syndrome associated with
      cardiopulmonary bypass in pediatric patients with the homozygous C4A null
      phenotype.
AB  - BACKGROUND: The mechanism of postoperative capillary leak syndrome related to
      cardiopulmonary bypass (CPB) is unknown. The authors hypothesized that C4 gene
      polymorphism might be involved in the development of the syndrome because
      complement activation is associated with CPB and protamine administration, and
      the two isotypes of C4 (C4A and C4B) differ in their biochemical and functional
      properties after activation. METHODS: One hundred fifty-six pediatric patients
      referred for elective cardiac surgery with CPB were included in the study. C4
      isotype studies were performed in plasma samples obtained before surgery, with
      use of agarose gel immunofixation and crossed immunoelectrophoresis. Five
      possible C4 phenotype groups were observed, which were abbreviated as follows:
      (1) AABB = no detectable null alleles, (2) A0BB = a single null allele
      (heterozygous) at the C4A locus, (3) 00BB = a homozygous C4A null allele, (4)
      AAB0 = a single null allele (heterozygous) at the C4B locus, and (5) AA00 = a
      homozygous C4B null allele. The patients were classified into five groups
      according to their C4 phenotypes. Before CPB and at 1 h after CPB, plasma protein
      was measured with a biuret test kit. Plasma colloid osmotic pressure was
      determined with a membrane osmometer. Evans blue dye was used to measure plasma
      volume, serum protein, intravenous protein pool, and transvascular escape rate of
      Evans blue dye. RESULTS: Of 156 pediatric patients enrolled, 80 were assigned to
      the AABB group, 28 were assigned to the A0BB group, 7 were assigned to the 00BB
      group, 31 were assigned to the AAB0 group, and 10 were assigned to the AA00
      group, according to their C4 phenotypes. At 1 h after CPB, serum protein
      concentrations averaged 3.6 +/- 0.4 g/dl in patients with the 00BB C4 phenotype;
      this value was significantly lower (P < 0.01) than that in patients with other C4
      phenotypes. The changes of intravenous protein pool and colloid osmotic pressure
      were comparable with the change in serum protein concentration. At 1 h after CPB,
      the transvascular escape rate of Evans blue dye averaged 11.5 +/- 1.3%/h in
      patients with the 00BB C4 phenotype; this value was significantly higher (P <
      0.01) than that in patients with other C4 phenotypes. CONCLUSIONS: In this study,
      capillary leak syndrome induced by CPB occurred only in patients with the
      homozygous C4A null phenotype.

PMID- 15166557
TI  - Infection control measures for operative procedures in severe acute respiratory
      syndrome-related patients.
AB  - BACKGROUND: Singapore reported its first case of Severe Acute Respiratory
      Syndrome (SARS) in early March 2003 and was placed on the World Health
      Organization's list of SARS-affected countries on March 15, 2003. During the
      outbreak, Tan Tock Seng Hospital was designated as the national SARS hospital in
      Singapore to manage all known SARS patients. Stringent infection control measures
      were introduced to protect healthcare workers and control intrahospital
      transmission of SARS. Work-flow processes for surgery were extensively modified.
      METHODS: The authors describe the development of infection control measures, the
      conduct of surgical procedures, and the management of high-risk procedures during
      the SARS outbreak. RESULTS: Forty-one operative procedures, including 15 high
      risk procedures (surgical tracheostomy), were performed on SARS-related patients.
      One hundred twenty-four healthcare workers had direct contact with SARS patients
      during these procedures. There was no transmission of SARS within the operating
      room complex. CONCLUSIONS: Staff personal protection, patient risk
      categorization, and reorganization of operating room workflow processes formed
      the key elements for the containment of SARS transmission. Lessons learned during
      this outbreak will help in the planning and execution of infection control
      measures, should another outbreak occur.

PMID- 15166558
TI  - Parental auricular acupuncture as an adjunct for parental presence during
      induction of anesthesia.
AB  - BACKGROUND: The purpose of this study was to determine whether parental auricular
      acupuncture reduces parental preoperative anxiety and thus allows children to
      benefit from parental presence during induction of anesthesia. METHODS: Mothers
      of children who were scheduled to undergo surgery were randomly assigned to an
      acupuncture intervention group (auricular press needles at relaxation,
      tranquilizer point, and master cerebral point) or a sham acupuncture control
      group (auricular press needles at the shoulder, wrist, and extraneous auricular
      point). The intervention was performed at least 30 min before the child's
      induction of anesthesia. All mothers were present during induction of anesthesia.
      The behavioral and physiologic anxiety of mothers and children were rated during
      the perioperative process. RESULTS: : Multivariable analysis examining maternal
      anxiety as a function of group found a group-by-time interaction (F1,65 = 4.1, P
      = 0.04). That is, after induction, maternal anxiety in the acupuncture group was
      significantly lower (42.9 +/- 10 vs. 49.5 +/- 11; P = 0.014). A multivariate
      model (F1,65 = 4.8, P =0.031) also showed that children whose mothers received
      the acupuncture intervention were significantly less anxious on entrance to the
      operating room (34.9 +/- 20 vs. 47.4 +/- 26; P = 0.03) and during introduction of
      the anesthesia mask (38.6 +/- 25 vs. 55.6 +/- 31; P = 0.016). There were no
      significant differences in maternal blood pressure and heart rate between the two
      groups. CONCLUSIONS: : Auricular acupuncture significantly decreased maternal
      anxiety during the preoperative period. Children of mothers who underwent
      acupuncture intervention benefitted from the reduction of maternal anxiety during
      the induction of anesthesia.

PMID- 15166559
TI  - Predictive performance and variability of the cardiac anesthesia risk evaluation
      score.
AB  - BACKGROUND: The Cardiac Anesthesia Risk Evaluation (CARE) score, a simple
      Canadian classification for predicting outcome after cardiac surgery, was
      evaluated in 556 consecutive patients in Paris, France. The authors compared its
      performance to those of two multifactorial risk indexes (European System for
      Cardiac Operative Risk Evaluation [EuroSCORE] and Tu score) and tested its
      variability between groups of physicians (anesthesiologists, surgeons, and
      cardiologists). METHODS: Each patient was simultaneously assessed using the three
      scores by an attending anesthesiologist in the immediate preoperative period. In
      a blinded study, the CARE score category was also determined by a cardiologist
      the day before surgery, by a surgeon in the operating room, and by a second
      anesthesiologist at arrival in intensive care unit. Calibration and
      discrimination for predicting outcomes were assessed by goodness-of-fit test and
      area under the receiver operating characteristic curve, respectively. The level
      of agreement of the CARE scoring between the three physicians was then assessed.
      RESULTS: The calibration analysis revealed no significant difference between
      expected and observed outcomes for the three classifications. The areas under the
      receiver operating characteristic curves for mortality were 0.77 with the CARE
      score, 0.78 with the EuroSCORE, and 0.73 with the Tu score (not significant). The
      agreement rate of the CARE scoring between two anesthesiologists, between
      anesthesiologists and surgeons, and between anesthesiologists and cardiologists
      were 90%, 83%, and 77%, respectively. CONCLUSIONS: Despite its simplicity, the
      CARE score predicts mortality and major morbidity as well the EuroSCORE. In
      addition, it remains devoid of significant variability when used by groups of
      physicians of different specialties.

PMID- 15166560
TI  - Injuries and liability related to central vascular catheters: a closed claims
      analysis.
AB  - BACKGROUND: To assess changing patterns of injury and liability associated with
      central venous or pulmonary artery catheters, the authors analyzed closed
      malpractice claims for central catheter injuries in the American Society of
      Anesthesiologists Closed Claims database. METHODS: All claims for which a central
      catheter (i.e., central venous or pulmonary artery catheter) was the primary
      damaging event for the injury were compared with the rest of the claims in the
      database. Central catheter complications were defined as being related to
      vascular access or catheter use or maintenance. Statistical analysis was
      performed using the chi-square test, Fisher exact test, or Z test (proportions)
      and the Kolmogorov-Smirnov test (payments). RESULTS: The database included 110
      claims for injuries related to central catheters (1.7% of 6,449 claims). Claims
      for central catheter injuries had a higher severity of injury, with an increased
      proportion of death (47%) compared with other claims in the database (29%, P <
      0.01). The most common complications were wire/catheter embolus (n = 20), cardiac
      tamponade (n = 16), carotid artery puncture/cannulation (n =16), hemothorax (n
      =15), and pneumothorax (n =14). Cardiac tamponade, hemothorax, and pulmonary
      artery rupture had a higher proportion of death (P < 0.05) compared with the rest
      of the central catheter injures. The proportion of claims for vascular access
      injury increased (47% to 84%) and use/maintenance injury decreased (53% to 16%)
      in 1994-1999 compared with 1978-1983 (P < 0.05). CONCLUSIONS: Claims related to
      central catheters had a high severity of patient injury. The most common
      complications causing injury were wire/catheter embolus, cardiac tamponade,
      carotid artery puncture/cannulation, hemothorax, and pneumothorax.

PMID- 15166561
TI  - Recovery from sleep deprivation occurs during propofol anesthesia.
AB  - BACKGROUND: Some neurophysiologic similarities between sleep and anesthesia
      suggest that an anesthetized state may reverse effects of sleep deprivation. The
      effect of anesthesia on sleep homeostasis, however, is unknown. To test the
      hypothesis that recovery from sleep deprivation occurs during anesthesia, the
      authors followed 24 h of sleep deprivation in the rat with a 6-h period of either
      ad libitum sleep or propofol anesthesia, and compared subsequent sleep
      characteristics. METHODS: With animal care committee approval,
      electroencephalographic/electromyographic electrodes and intrajugular cannulae
      were implanted in 32 rats. After a 7-day recovery and 24-h baseline
      electroencephalographic/electromyographic recording period, rats were sleep
      deprived for 24 h by the disk-over-water method. Rats then underwent 6 h of
      either propofol anesthesia (n = 16) or ad libitum sleep with intralipid
      administration (n = 16), followed by electroencephalographic/electromyographic
      monitoring for 72 h. RESULTS: In control rats, increases above baseline in non
      rapid eye movement sleep, rapid eye movement sleep, and non-rapid eye movement
      delta power persisted for 12 h after 24 h of sleep deprivation. Recovery from
      sleep deprivation in anesthetized rats was similar in timing to that of controls.
      No delayed rebound effects were observed in either group for 72 h after
      deprivation. CONCLUSION: These data show that a recovery process similar to that
      occurring during naturally occurring sleep also takes place during anesthesia and
      suggest that sleep and anesthesia share common regulatory mechanisms. Such
      interactions between sleep and anesthesia may allow anesthesiologists to better
      understand a potentially important source of variability in anesthetic action and
      raise the possibility that anesthetics may facilitate sleep in environments where
      sleep deprivation is common.

PMID- 15166562
TI  - Measurement of oxygen uptake and carbon dioxide elimination using the bymixer:
      validation in a metabolic lung simulator.
AB  - BACKGROUND: The authors have developed a new clinical bymixer that bypasses a
      constant fraction of gas flow through a mixing arm. A separate bymixer was
      interposed in the expiratory and inspiratory limbs of the ventilation circuit to
      measure mixed gas fractions. By utilizing nitrogen conservation, the clinical
      bymixer allows the determination of airway carbon dioxide elimination (VCO2) and
      oxygen uptake (VO2), whenever basic expired flow and gas monitoring measurements
      are used for the patient. Neither an expiratory exhaust gas collection bag nor
      expensive, complex equipment are needed. This study tested the accuracy of airway
      bymixer-flow measurements of VCO2 and VO2 in a new bench apparatus. METHODS: The
      authors compared airway bymixer-flow measurements of VCO2 and VO2 over a range of
      reference values generated by ethanol combustion in a new metabolic lung
      simulator, which was ventilated by a volume-cycled respirator. An airway humidity
      and temperature sensor permitted standard temperature and pressure, dry,
      correction of airway VCO2 and VO2. RESULTS: Bymixer-flow airway measurements of
      VCO2 and VO2 correlated closely (R2 = 0.999 and 0.998, respectively) with the
      stoichiometric values generated by ethanol combustion. Limits of agreement for
      VCO2 and VO2 were 0.1 +/- 4.7 and 1.1 +/- 5.7%, respectively. The average (+/-
      SD) percent error for airway VCO2 (compared with the stoichiometric value) was
      0.1 +/- 2.4%. The same error for airway VO2 was 1.1 +/- 2.9%. CONCLUSIONS: The
      new clinical bymixer, plus basic expired flow and gas fraction measurements,
      generated clinically accurate determinations of VCO2 and VO2. These measurements
      are helpful in the assessment of metabolic gas exchange in the critical care
      unit. In contrast to using the gas collection bag or complex metabolic monitor,
      the bymixer should measure mixed gas concentrations in the inspired or expired
      limb of the common anesthesia circle ventilation circuit.

PMID- 15166563
TI  - Gamma-aminobutyric acid type A receptor beta 2 subunit mediates the hypothermic
      effect of etomidate in mice.
AB  - BACKGROUND: The authors have previously described that the gamma-aminobutyric
      acid type A (GABAA) receptor beta 2N265S mutation results in a knock-in mouse
      with reduced sensitivity to etomidate. After recovery from etomidate anesthesia,
      these mice have improved motor performance and less slow wave sleep. Because most
      clinically used anesthetics produce hypothermia, the effect of this mutation on
      core body temperature was investigated. METHODS: The effect of etomidate and
      propofol on core body temperature were measured using radiotelemetry in freely
      moving GABAA receptor beta 2N265S mutant mice and wild-type controls. RESULTS:
      beta 2N265S mutant mice have a reduced hypothermic response to anesthetic doses
      of etomidate compared with wild-type controls and after a transient loss of
      righting reflex regain normothermia more rapidly compared with wild-type
      controls. Subanesthetic doses of etomidate produce hypothermia, which was not
      observed in the mutant mice. Vehicle administration resulted in a stress-induced
      hyperthermic response in both genotypes. Propofol produced a hypothermic response
      that was similar in both genotypes. CONCLUSIONS: The GABAA receptor beta 2
      subunit mediates a significant proportion of the hypothermic effects of
      etomidate. As the beta 2 subunit mediates postrecovery ataxia and sedation,
      anesthetic agents that do not have in vivo potency at beta 2 subunit-containing
      receptors offer the potential for surgical anesthesia with improved recovery
      characteristics.

PMID- 15166565
TI  - Effects of imposed acid-base derangement on the cardiovascular effects and
      pharmacokinetics of bupivacaine and thiopental.
AB  - BACKGROUND: By changing physicochemical properties such as effective
      lipophilicity, changes in blood pH could alter the distribution, elimination, and
      effects of weakly ionizing drugs. The authors examined the outcome of imposed
      acid-base derangement on cardiovascular effects and myocardial and whole body
      pharmacokinetics of bupivacaine, a weak base, and thiopental, a weak acid.
      METHODS: Intravenous infusions of rac-bupivacaine HCl (37.5 mg) or rac-thiopental
      sodium (250 mg, subanesthetic dose) were administered over 3 min to previously
      instrumented conscious ewes with normal blood pH, acidemia imposed by lactic acid
      infusion, or alkalemia imposed by bicarbonate infusion. Hemodynamic and
      electrocardiographic effects were recorded; arterial and coronary sinus drug
      blood concentrations were analyzed by chiral high-performance liquid
      chromatography. RESULTS: Bupivacaine decreased myocardial contractility, coronary
      perfusion, heart rate, and cardiac output; however, cardiac output and stroke
      volume were not as affected by bupivacaine with acidemia. Thiopental decreased
      myocardial contractility and stroke volume and increased heart rate; acidemia
      enhanced the tachycardia and produced a greater decrease in stroke volume than
      with alkalemia. Taken as a whole, the cardiovascular changes were not
      systematically modified by acid-base derangement. Overall, the tissue
      distribution of bupivacaine was favored by alkalemia, but thiopental
      pharmacokinetics were essentially unaffected by acid-base derangement. Acid-base
      derangement did not influence the kinetics of either drug enantioselectively.
      CONCLUSIONS: At the doses used, the hemodynamic and electrocardiographic effects
      of bupivacaine and thiopental were not systematically modified by acid-base
      derangement, nor were there changes in regional or whole body pharmacokinetics of
      either drug that were clearly related to acid-base status.

PMID- 15166564
TI  - Endotracheal tubes coated with antiseptics decrease bacterial colonization of the
      ventilator circuits, lungs, and endotracheal tube.
AB  - BACKGROUND: Formation of a bacterial biofilm within the endotracheal tube (ETT)
      after tracheal intubation is rapid and represents a ready source of lung
      bacterial colonization. The authors investigated bacterial colonization of the
      ventilator circuit, the ETT, and the lungs when the ETT was coated with silver
      sulfadiazine and chlorhexidine in polyurethane, using no bacterial/viral filter
      attached to the ETT. METHODS: Sixteen sheep were randomized into two groups.
      Eight sheep were intubated with a standard ETT (control group), and eight were
      intubated with a coated ETT (study group). Animals were mechanically ventilated
      for 24 h. At autopsy, the authors sampled the trachea, bronchi, lobar parenchyma,
      and ETT for quantitative bacterial cultures. Qualitative bacterial cultures were
      obtained from the filter, humidifier, inspiratory and expiratory lines, and water
      trap. ETTs were analyzed with light microscopy, scanning electron microscopy, and
      laser scanning confocal microscopy. RESULTS: In the control group, all eight ETTs
      were heavily colonized (10(5)-10(8) colony-forming units [cfu]/g), forming a
      thick biofilm. The ventilator circuit was always colonized. Pathogenic bacteria
      colonized the trachea and the lungs in five of eight sheep (up to 10(9) cfu/g).
      In the study group, seven of eight ETTs and their ventilator circuits showed no
      growth, with absence of a biofilm; one ETT and the respective ventilator circuit
      showed low bacterial growth (10(3)-10(4) cfu/g). The trachea was colonized in
      three sheep, although lungs and bronchi showed no bacterial growth, except for
      one bronchus in one sheep. CONCLUSIONS: Coated ETTs induced a nonsignificant
      reduction of the tracheal colonization, eliminated (seven of eight) or reduced
      (one of eight) bacterial colonization of the ETT and ventilator circuits, and
      prevented lung bacterial colonization.

PMID- 15166566
TI  - Continuous, noninvasive, and localized microvascular tissue oximetry using
      visible light spectroscopy.
AB  - BACKGROUND: The authors evaluated the ability of visible light spectroscopy (VLS)
      oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike
      near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses
      shallow-penetrating visible light to measure microvascular hemoglobin oxygen
      saturation (StO2) in small, thin tissue volumes. METHODS: In pigs, StO2 was
      measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%),
      and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle,
      and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia
      (occlusion, compression, ventricular fibrillation). RESULTS: In pigs, normoxic
      StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and
      decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31
      +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at
      different sites (733 measures, 111 subjects); for each noninvasive site except
      skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects;
      buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2
      (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially
      decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94).
      Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS
      saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35%
      during ischemia). CONCLUSIONS: VLS oximetry provides a continuous, noninvasive,
      and localized measurement of the StO2, sensitive to hypoxemia, regional, and
      global ischemia. The reproducible and narrow StO2 normal range for oral/enteric
      mucosa supports use of this site as an accessible and reliable reference point
      for the VLS monitoring of systemic flow.

PMID- 15166567
TI  - Measurement of cardiac output with indocyanine green transcutaneous fluorescence
      dilution technique.
AB  - BACKGROUND: Cardiac output is an essential parameter for the hemodynamic
      assessment of patients with cardiovascular disease. The authors tested in an
      animal model the feasibility of measuring cardiac output by transcutaneous
      fluorescence monitoring of an intravenous bolus injection of indocyanine green.
      METHODS: Fluorescence dilution cardiac output was measured in 10 anesthetized
      rabbits and compared with cardiac output measured with a pulmonary thermodilution
      catheter and to aortic velocity measured by Doppler ultrasound. Indocyanine green
      fluorescence was excited with a near-infrared laser and measured with an optical
      probe positioned on the central ear artery. Measurements were obtained during
      baseline conditions as well as during short-term decreases and increases of the
      cardiac output. RESULTS: The fluorescence of circulating indocyanine green
      detected transcutaneously varied proportionally to that of arterial blood
      samples, which allowed for calibration in terms of blood concentration of
      indocyanine green. Average values of fluorescence dilution cardiac output and
      thermodilution cardiac output measured in baseline conditions were 412 (+/- 13)
      and 366 (+/- 11) ml/min, respectively. Fluorescence dilution cardiac output
      showed a close, one-to-one linear relation with thermodilution cardiac output in
      each animal and in the pooled data from all animals (slope = 0.95 x 0.03; R =
      0.94). Fluorescence dilution cardiac output overestimated thermodilution cardiac
      output by an average of 46 (+/- 6) ml/min during baseline conditions.
      Fluorescence dilution cardiac output was tightly correlated with aortic velocity.
      CONCLUSIONS: The proposed technique yielded accurate estimates of the cardiac
      output in experimental animals. This study should provide an initial framework
      for clinical testing of this new minimally invasive method for measuring cardiac
      output.

PMID- 15166568
TI  - Recombinant human hemoglobin with reduced nitric oxide-scavenging capacity
      restores effectively pancreatic microcirculatory disorders in hemorrhagic shock.
AB  - BACKGROUND: Scavenging of nitric oxide by hemoglobin-based oxygen carriers could
      aggravate microcirculatory failure in splanchnic organs after hemorrhagic shock
      as a consequence of vasoconstrictive side effects. The aim of this study was to
      compare the effects of two recombinant human hemoglobin solutions, a second
      generation product bearing reduced nitric oxide-scavenging properties (rHb2.0)
      due to site directed mutagenesis of the heme pocket and a first-generation
      recombinant hemoglobin (rHb1.1) with scavenging capacity similar to native
      hemoglobin, on the pancreatic microcirculation after hemorrhagic shock. METHODS:
      Twenty-eight pentobarbital-anesthetized rats were bled to a mean arterial
      pressure of 40 mmHg and maintained at this level for 1 h. Using an intravital
      microscope, the length of erythrocyte-perfused pancreatic capillaries per
      observation area (functional capillary density) were measured in animals
      resuscitated by volumes of hydroxyethyl starch, rHb1.1, or rHb2.0 equivalent to
      the shed blood volume. Animals without shock induction served as control.
      RESULTS: As compared with control (438 +/- 10 cm(-1)), animals treated with
      hydroxyethyl starch (315 +/- 44 cm(-1)) and rHb1.1 (288 +/- 67 cm(-1)) showed a
      significant reduction of functional capillary density after 2 h of resuscitation.
      rHb2.0 was able to restore functional capillary density (410 +/- 42 cm(-1)) and
      mean arterial pressure to baseline values. CONCLUSION: rHb2.0 was effectively
      able to restore pancreatic microcirculation after hemorrhagic shock. This may be
      related to the compound's effective lack of nitric oxide-scavenging properties.
      This hemoglobin solution or ones similar to it might be uniquely valuable for
      resuscitation from hemorrhagic shock.

PMID- 15166569
TI  - Epidural catheter penetration of human dural tissue: in vitro investigation.
AB  - BACKGROUND: Factors contributing to subarachnoid catheter passage after epidural
      placement are not well understood. This study explored mechanisms that might
      explain its occurrence. METHODS: Human cadaveric dura was mounted on a model and
      pressurized to physiologic levels. In a standardized fashion, a 20-gauge Portex
      three-port, closed end (nonflexible) tip catheter was passed through an epidural
      needle mounted on a micromanipulator at a 90 degree angle, attempting to
      penetrate dura with the catheter. Attempts then followed with a 19-gauge Arrow
      Flex Tip Plus single-port catheter. Subarachnoid catheter passage was compared in
      (1) intact dura, (2) clinically occult versus obvious epidural needle punctures,
      and (3) single 25-gauge Whitacre spinal needle punctures after combined spinal
      epidural placement. RESULTS: Neither catheter penetrated intact dura: Portex, 0
      of 300 attempts (0.0000; 95% confidence interval [CI]: 0.0000, 0.0158); Arrow, 0
      of 300 attempts (0.0000; 95% CI: 0.0000, 0.0158). In clinically occult epidural
      needle punctures, the 20-gauge Portex catheter penetrated 1 of 3 specimens in 1
      of 14 attempts (0.0714; 95% CI: 0.0021, 0.3583). The 19-gauge Arrow did not pass
      (0 of 15 attempts, 0.0000; 95% CI: 0.0000, 0.2535). In clinically obvious
      epidural needle punctures, the Portex passed in 6 of 33 attempts (0.1818; 95% CI:
      0.0760, 0.3608) and the Arrow passed in 1 of 35 attempts (0.0286; 95% CI: 0.0012,
      0.1662). Neither catheter passed through a single 25-gauge spinal needle puncture
      after an uncomplicated combined spinal-epidural: Portex, 0 of 90 attempts
      (0.0000; 95% CI: 0.0000, 0.0510); Arrow, 0 of 90 attempts (0.0000; 95% CI:
      0.0000, 0.0510). CONCLUSIONS: Catheter passage is unlikely in the presence of
      intact dura or after an uncomplicated combined spinal-epidural. Unintentional
      subarachnoid passage suggests dural damage with the epidural needle.

PMID- 15166570
TI  - Intrathecal opioids and lower urinary tract function: a urodynamic evaluation.
AB  - BACKGROUND: Intrathecal administration of opioids may cause lower urinary tract
      dysfunction. In this study, the authors compared the effects of morphine and
      sufentanil administered intrathecally in a randomized double-blind fashion (two
      doses each) on lower urinary tract function in healthy male volunteers. METHODS:
      Urodynamic evaluation was performed before and every hour after drug
      administration up to complete recovery of lower urinary tract function using
      pressure and flow measurements recorded from catheters in the bladder and rectum.
      Sense of urge and urinary flow rates were assessed every hour by filling the
      bladder with its cystometric capacity and asking the patient to void. Full
      recovery was defined as a residual volume of less than 10% of bladder capacity
      and a maximum flow rate within 10% of the initial value. RESULTS: Intrathecal
      administration of both opioids caused dose-dependent suppression of detrusor
      contractility and decreased sensation of urge. Mean times to recovery of normal
      lower urinary tract function were 5 and 8 h after 10 or 30 microg sufentanil and
      14 and 20 h after 0.1 or 0.3 mg morphine, respectively. This recovery profile can
      be explained by the spinal pharmacokinetics of both opioids. CONCLUSIONS:
      Intrathecal opioids decrease bladder function by causing dose-dependent
      suppression of detrusor contractility and decreased sensation of urge. Recovery
      of normal lower urinary tract function is significantly faster after intrathecal
      sufentanil than after morphine, and the recovery time is clearly dose dependent.

PMID- 15166571
TI  - Correlation between the distribution of contrast medium and the extent of
      blockade during epidural anesthesia.
AB  - BACKGROUND: If the epidural spread of contrast medium can be well correlated with
      the spread of local anesthetics, epidurography can predict the dermatomal
      distribution of the anesthetic block. The authors evaluated the relation between
      radiographic and analgesic spread. METHODS: An epidural catheter was inserted in
      90 patients, and predicted catheter tip position was recorded. The analgesic area
      was determined by pinprick after a 5-ml injection of 1.5% lidocaine, and
      epidurography was performed after a 5-ml injection of 240 mg I/ml iotrolan.
      Patients were assigned to three groups according to catheter tip position (group
      C: C-T4; group T: T5-T10; group L: T11-L), and patterns of spread were compared.
      In 16 of 90 subjects, radiographic and analgesic spread was further investigated
      after an additional 5-ml injection of iotrolan and lidocaine. RESULTS: The total
      radiographic spread correlated well with analgesic spread (right side: Y = 0.84 X
      + 0.16, r = 0.92, P < 0.01; left side: Y = 0.78 X + 0.45, r = 0.91, P < 0.01).
      The mean radiographic spread in the cephalad and caudal directions from the
      catheter tip also correlated well with mean analgesic spread (r = 0.97, P < 0.01,
      each direction). The mean distance between the predicted catheter tip and
      radiographically determined positions was 1.0 +/- 0.8 segments: the value in
      group T was significantly larger than that in groups C (P < 0.05) and L (P <
      0.01). Although the correlation of radiographic spread with age was statistically
      significantly (r = 0.39, P < 0.01), great individual variation in spreading
      pattern was seen. In 16 subjects, mean radiographic spread correlated well with
      analgesic spread after 5- and 10-ml injections of iotrolan and lidocaine.
      CONCLUSIONS: Epidurography is useful to indicate epidural catheter position and
      can help to predict the exact dermatomal distribution of analgesic block.

PMID- 15166572
TI  - Phase Ia and Ib study of amitriptyline for ulnar nerve block in humans: side
      effects and efficacy.
AB  - BACKGROUND: The antidepressant amitriptyline is used as an adjuvant in the
      treatment of chronic pain conditions. Among its many actions, this drug also
      blocks ion channels, such as Na channels. Preliminary animal studies suggested
      that amitripty-line would be a longer-lasting local anesthetic than bupivacaine,
      with potentially fewer side effects. Therefore, the authors investigated the
      adverse effects and effectiveness of this drug when given for ulnar nerve
      blockade in human volunteers. METHODS: After obtaining written institutional
      review board approval and informed consent, a typical phase Ia trial was
      conducted by administration to the ulnar nerve at the level of the wrist in an
      open-label, dose-escalating fashion. Amitripty-line hydrochloride, 4 ml, at
      concentrations of 5, 10, and 20 mM (n = 4-9/group) was used for each volunteer.
      If no major side effects and nerve block were encountered, comparison in a
      randomized, double-blinded trial of amitriptyline (20 mM) to placebo and
      bupivacaine (4 mM) (n = 4-9/group), was to follow. A blunt needle was used to
      grade the pain, and motor blockade was assessed by the Froment test. RESULTS:
      There was no significant statistical difference in terms of side effects (pain,
      swelling, erythema, and sedation) among any groups. The analgesic effects of 20
      mM amitriptyline and 4 mm bupivacaine solution were significantly higher than
      those of the placebo solution. CONCLUSIONS: Because of the lack of evidence that
      amitripty-line provides better nerve blockade than current local anesthetics and
      the potential for neurotoxicity, its use for peripheral nerve blockade in humans
      seems limited.

PMID- 15166573
TI  - Amitriptyline neurotoxicity: dose-related pathology after topical application to
      rat sciatic nerve.
AB  - BACKGROUND: Amitriptyline is a tricyclic antidepressant drug used systemically
      for the management of neuropathic pain. Antidepressants, as a class of drugs with
      direct neurologic actions, are becoming widely used for the management of chronic
      pain, although their mechanisms are not entirely understood. Amitriptyline exerts
      potent effects on reuptake of norepinephrine and serotonin and blocks alpha 2A
      adrenoreceptors and N-methyl-D-aspartate receptors. Because amitriptyline is also
      a particularly potent blocker of sodium channels and voltage-gated potassium and
      calcium channels, it has been recommended as a long-acting local anesthetic
      agent. Unfortunately, amitriptyline has significant toxic side effects in the
      central nervous system and cardiovascular system that are dose-related to its
      systemic administration. Therefore, before amitriptyline can be used clinically
      as a local anesthetic agent, it should be thoroughly explored with respect to its
      direct neurotoxic effect in the peripheral nervous system. METHODS: The left
      sciatic nerve of Sprague-Dawley rats (12/ group) received a single topical
      amitriptyline dose of 0.625, 1.25, 2.5, or 5 mg; a saline group (n = 2) was used
      as control. Neuropathologic evaluations were conducted in separate animals (n =
      4) 1, 3, and 7 days later. RESULTS: Amitriptyline topically applied in vivo to
      rat sciatic nerve causes a dose-related neurotoxic effect. Drug doses of 0.625-5
      mg all caused Wallerian degeneration of peripheral nerve fibers, with the number
      of affected fibers and the severity of the injury directly related to the dose.
      CONCLUSION: Because the effective local anesthetic dose is within this dose
      range, the authors strongly recommend that amitriptyline not be used as a local
      anesthetic agent.

PMID- 15166574
TI  - Electrical nerve localization: effects of cutaneous electrode placement and
      duration of the stimulus on motor response.
AB  - BACKGROUND: Recommendations regarding the technical aspects of nerve stimulator
      assisted nerve localization are conflicting. The objectives of this study were to
      determine whether the placement of the cutaneous electrode affects nerve
      stimulation and to determine the duration and intensity of an electrical stimulus
      that allows nerve stimulation with minimal discomfort. METHODS: Ten healthy
      volunteers underwent an interscalene and a femoral nerve block. After obtaining a
      clearly visible motor response of the biceps (interscalene) and quadriceps
      (femoral) muscles at the minimal current (0.1 ms, 2 Hz), the position of the
      cutaneous electrode was varied. Next, the duration of the stimulating current was
      set at 0.05, 0.1, 0.3, 0.5, or 1.0 ms, in random order. Intensity of the motor
      response and discomfort on stimulation were recorded. RESULTS: The minimal
      current at which a visible motor response was obtained was 0.32 +/- 0.1 mA (0.23
      0.38 mA) for the inter-scalene block and 0.29 +/- 0.1 mA (0.15-0.4 mA) for the
      femoral block. Changing the position of the return electrodes did not result in
      any change in the grade of the motor response or in the current required to
      maintain it. Currents of longer duration caused discomfort and more forceful
      contraction at a lower current intensity as compared with currents of shorter
      duration (P < 0.01). When the current was adjusted to maintain the same visible
      motor response, there was no significant discomfort among studied current
      durations. CONCLUSION: Site of placement of the cutaneous electrode is not
      important when constant current nerve stimulators are used during nerve
      localization in regional anesthesia. There is an inverse relation between the
      current required to obtain a visible motor response and current duration.
      Selecting a current duration between 0.05 and 1.0 ms to specifically stimulate
      sensory or motor components of a mixed nerve does not seem to be important in
      clinical practice.

PMID- 15166575
TI  - Remifentanil directly activates human N-methyl-D-aspartate receptors expressed in
      Xenopus laevis oocytes.
AB  - BACKGROUND: Clinical studies suggest that intraoperative administration of the
      clinical remifentanil formulation Ultiva (GlaxoWellcome GmbH & Co, Bad Oldesloe,
      Germany) increases postoperative pain and postoperative analgesic requirements,
      but mechanisms remain unclear. N-methyl-D-aspartate (NMDA) receptors are thought
      to play a major role in development of postoperative pain and opiate tolerance.
      The authors hypothesized that Ultiva directly stimulates human NMDA receptors.
      METHODS: To test this hypothesis, the authors expressed human NR1A/NR2A and
      NR1A/NR2B NMDA receptors in Xenopus laevis oocytes by injection of messenger RNA
      prepared in vitro. After protein expression, they used a two-electrode voltage
      clamp to measure currents induced by NMDA receptor agonists and opioids. RESULTS:
      Noninjected cells were unresponsive to all compounds tested. Glutamate/glycine (1
      nM-1 mM each) or Ultiva (0.01 pM-0.1 mM) stimulated NMDA receptors concentration
      dependently. NR1A/2A EC50 values were 8.0 microM/12 microM for glutamate/glycine
      and 3.5 nM for Ultiva, and NR1A/2B EC50 values were 3.9 microM/1.9 microM for
      glutamate/glycine and 0.82 microM for Ultiva. Glycine in combination with Ultiva
      showed no additive effect compared with Ultiva alone. Ultiva-induced currents
      were inhibited by MK-801 (pore blocker) but not by 7-CK (glycine antagonist), D
      AP5 (glutamate antagonist), or naloxone. Fentanyl (10 microM) did not stimulate
      NMDA receptors. CONCLUSION: These data indicate that Ultiva but not fentanyl
      stimulates NMDA receptors of different subunit combinations (NR1A/2A, NR1A/2B).
      The mechanism seems to be allosteric activation of the NMDA receptor.

PMID- 15166577
TI  - Low doses of fentanyl block central sensitization in the rat spinal cord in vivo.
AB  - BACKGROUND: mu-Opioid receptor agonists are strong analgesics. However, their
      usefulness for preemptive analgesia is controversial. The authors tested
      antinociceptive and preemptive properties of fentanyl as a mu-opioid receptor
      agonist in a model of spinal nociception in vivo. METHODS: C fiber-evoked
      potentials were recorded in the superficial laminae I-II of the rat lumbar spinal
      cord with glass microelectrodes in response to electrical stimulation of the
      sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to
      induce long-term potentiation of C fiber-evoked field potentials, a form of
      central sensitization. To test the effect of fentanyl on acute nociception,
      fentanyl was infused intravenously at increasing doses (6-192 microg.kg(-1).h(
      1)). One hour after start of infusion, high-frequency stimulation was applied to
      evaluate effects of fentanyl on the induction of long-term potentiation. RESULTS:
      In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked
      field potentials to 149 +/-12% of controls (mean +/-SEM; n = 6) for at least 1 h.
      Increasing doses of fentanyl led to a significant reduction of C fiber-evoked
      potentials in a dose-dependent manner. The induction of long-term potentiation
      was blocked by low doses of fentanyl (infusion 12-48 microg.kg(1).h(-1)). At high
      doses, fentanyl did not block the induction of long-term potentiation (infusion
      96-192 microg.kg(-1).h(-1)). CONCLUSIONS: : Low doses of fentanyl block the
      synaptic form of central sensitization in the rat spinal cord in vivo, but higher
      doses do not have this effect.

PMID- 15166576
TI  - Production of paradoxical sensory hypersensitivity by alpha 2-adrenoreceptor
      agonists.
AB  - BACKGROUND: Administration of opioid receptor agonists is followed by paradoxical
      sensory hypersensitivity. This hypersensitivity has been suggested to contribute
      to the antinociceptive tolerance observed with opioids. The authors hypothesized
      that alpha 2-adrenoreceptor agonists, which also produce antinociceptive
      tolerance, would produce sensory hypersensitivity. METHODS: alpha 2
      Adrenoreceptor agonists were administered to male Sprague-Dawley rats as a single
      subcutaneous injection, a continuous subcutaneous infusion, a single intrathecal
      injection, or a continuous intrathecal infusion. Thermal sensitivity was
      determined using latency to withdrawal of the hind paw from radiant heat. Tactile
      sensitivity was determined using withdrawal threshold to von Frey filaments.
      Spinal dynorphin content was measured by enzyme immunoassay. RESULTS: Single
      systemic or intrathecal injections of clonidine or dexmedetomidine produced
      antinociception followed by delayed thermal and tactile hypersensitivity. Six-day
      systemic or intrathecal infusion of clonidine produced tactile and thermal
      hypersensitivity observed even during clonidine infusion. Sensory
      hypersensitivity was prevented by coadministration of the alpha 2-adrenoreceptor
      selective antagonist idazoxan or the N-methyl-D-aspartate receptor-selective
      antagonist MK-801. Six-day infusion of intrathecal clonidine increased dynorphin
      content in dorsal lumbar spinal cord. MK-801 and dynorphin antiserum reversed
      clonidine-induced sensory hypersensitivity. CONCLUSIONS: alpha 2-Adrenoreceptor
      agonists produce sensory hypersensitivity that may be analogous to that produced
      by opioids. Sensory hypersensitivity was prevented by idazoxan, demonstrating
      that it is mediated by alpha 2 receptors. Clonidine infusion increased spinal
      dynorphin content. Sensory hypersensitivity was prevented or reversed by MK-801
      and dynorphin antiserum, implicating N-methyl-D-aspartate receptors and spinal
      dynorphin in its production. Clinicians should be mindful of the possibility of
      drug-induced hyperalgesia in patients treated with alpha 2-adrenoreceptor
      agonists.

PMID- 15166578
TI  - Differentiating among hospitals performing physiologically complex operative
      procedures in the elderly.
AB  - BACKGROUND: The authors previously showed how a statewide discharge abstract
      database could be used to quantify for stakeholders how surgical practices differ
      among hospitals. The two pediatric hospitals in Iowa differ from other hospitals
      in Iowa based on their providing a more diverse, comprehensive, and
      physiologically complex selection of procedures in younger patients.
      Physiologically complex surgery performed in children aged 0-2 yr has been
      regionalized to a few high-volume facilities. METHODS: The same inpatient
      discharge abstract database was used to quantify physiologically complex
      operative procedures performed throughout Iowa in patients aged 80 yr and older
      during January through June 2001. RESULTS: In contrast to earlier results with
      pediatric patients using the same database, hospitals performing physiologically
      complex procedures in the elderly could not readily be differentiated from one
      another based on the numbers and types of procedures performed (P < 0.001 when
      comparing geriatrics vs. pediatrics in terms of the distributions of numbers of
      procedures, the distributions of numbers of different types of procedures, or the
      distributions of numbers of rare procedures performed at different hospitals).
      Additional analyses showed that one hospital did perform relatively more rare
      procedures in geriatric patients and had a relatively larger percentage of
      patients who traveled beyond their local county to reach it. CONCLUSIONS: Results
      observed for geriatric patients provide further evidence of the validity of these
      methods and the usefulness of discharge abstract data for comparing surgical
      practices among facilities. A hospital can use discharge abstract data to assist
      governmental agencies, charitable organizations, philanthropists, insurers, etc.,
      in appreciating the unique contributions of individual hospitals to surgical
      care.

PMID- 15166579
TI  - Candidate gene studies of human pain mechanisms: methods for optimizing choice of
      polymorphisms and sample size.

PMID- 15166580
TI  - Practice guidelines for acute pain management in the perioperative setting: an
      updated report by the American Society of Anesthesiologists Task Force on Acute
      Pain Management.

PMID- 15166581
TI  - Prevention and management of intrathecal drug delivery and spinal cord
      stimulation system infections.

PMID- 15166582
TI  - Cervical transforaminal injection of steroids.

PMID- 15166583
TI  - Successful pregnancy and cesarean delivery 22 years after separation in an
      ischiopagus tetrapus conjoined twin.

PMID- 15166584
TI  - Peripartum substitution of inhaled for intravenous prostacyclin in a patient with
      primary pulmonary hypertension.

PMID- 15166585
TI  - Preadmission anesthesia consultation using telemedicine technology: a pilot
      study.

PMID- 15166586
TI  - Neonatal effects of long-term maternal phenoxybenzamine therapy.

PMID- 15166587
TI  - Interaction of spinal nitric oxide and prostaglandins after L5-L6 spinal nerve
      ligation in the rat: an isobolographic analysis.

PMID- 15166588
TI  - Steroidal nondepolarizing muscle relaxants do not simulate the effects of
      glucocorticoids on glucocorticoid receptor-mediated transcription in cultured
      skeletal muscle cells.

PMID- 15166589
TI  - Which troponin I peak concentration?

PMID- 15166591
TI  - Cerebrospinal fluid physiology and cerebrospinal fluid drainage.

PMID- 15166593
TI  - Using the visual analog scale.

PMID- 15166596
TI  - Increased margin of safety of morphine-6-glucuronide relative to morphine.

PMID- 15166597
TI  - Interdental distance and direct laryngoscopy.

PMID- 15166598
TI  - Mouth opening, craniocervical extension, and laryngoscopic positioning.

PMID- 15166600
TI  - Patient positioning and ultrasound guidance are important in bilateral
      cannulation of internal jugular veins.

PMID- 15166601
TI  - A 4.42% reduction in the cross-sectional area of a jugular vein cannot result in
      doubling of the intracranial pressure.

PMID- 15166603
TI  - Do we need a low dose of succinylcholine to facilitate intubation in teaching
      hospitals?

PMID- 15166604
TI  - What is the correct dose of succinylcholine?

PMID- 15166605
TI  - Should the intubating dose of succinylcholine be revisited?

PMID- 15166606
TI  - Optimal intubating dose of succinylcholine.

PMID- 15166609
TI  - Outbreak of severe acute respiratory syndrome in Singapore and modifications in
      the anesthesia service.

PMID- 15166610
TI  - Modified protective suits for anesthesiologists performing tracheal intubation
      for severe acute respiratory syndrome patients in Taiwan.

PMID- 15166611
TI  - Unanticipated difficult intubation due to significant change in mobility at the
      neck and jaw on assuming supine position.

PMID- 15166614
TI  - Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity.
AB  - Flavopiridol has potent anti-proliferative properties due to its direct action of
      binding to the ATP-binding pocket of cyclin-dependent kinases (cdks), and due to
      its indirect action reducing levels of other cyclins and cdk inhibitors,
      contributing to its pleiotropic effects. Flavopiridol is a potent apoptotic agent
      due to its ability to cause cell death in cycling as well as non-cycling tumor
      cells; to down-regulate important cell survival proteins, such as survivin,
      through inhibition of the phosphorylation of Thr34; to increase sensitivity for S
      phase cells to drug treatment by modulating E2F-1 transcription factor activity
      in tumor cells; to induce both caspase-dependent and -independent mitochondrial
      cell death pathways; and to inhibit the activation of p-Akt which in turn
      inhibits activation of NF-kappaB. Flavopiridol possesses several important anti
      angiogenic activities including induction of apoptosis of endothelial cells;
      inhibition of the hypoxic induction of vascular endothelial growth factor and/or
      its production under hypoxic conditions through inhibition of HIF-1alpha
      transcription; and decreased secretion of matrix metalloproteinases that is
      linked with significant inhibition of invasive potential in Matrigel assays.
      Taken together, the anti-proliferative and anti-angiogenic properties of
      flavopiridol may contribute to its anti-tumor activities observed in several
      preclinical animal models of human cancers including prostate, lymphoid, head and
      neck, colon, and glioma. These promising preclinical observations opened the way
      for phase I and II clinical trials. Given the low toxicity profile of
      flavopiridol used as a single agent in patients, combination therapy now offers
      numerous opportunities in the near future to improve the efficacy of flavopiridol
      in the treatment of refractory cancers.

PMID- 15166615
TI  - DNA repair pathways in drug resistance in melanoma.
AB  - Metastatic melanoma has a poor prognosis due to resistance to multiple
      chemotherapy regimens. The mainstay of treatment remains dacarbazine, with
      cisplatin being a commonly used alternative. Melanoma displays marked resistance
      to the DNA-damaging effects of these drugs. Intrinsic and acquired resistance
      involves multiple cellular pathways of damage recognition, repair and apoptosis.
      Increased understanding of these pathways is identifying novel targets that it is
      hoped will make inroads into the treatment of this lethal disease.

PMID- 15166616
TI  - Therapy for unresectable hepatocellular carcinoma: review of the randomized
      clinical trials-I: hepatic arterial embolization and embolization-based therapies
      in unresectable hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is common worldwide and frequently fatal. Despite
      the availability of potentially curative therapies for localized HCC, most
      patients have unresectable tumor, either at presentation or recurrence. We
      reviewed 18 randomized trials investigating hepatic arterial embolization-based
      therapies. Therapy for unresectable HCC is difficult, both because of advanced
      stage at presentation and accompanying liver dysfunction. Clinical investigations
      in HCC have been impaired by heterogeneity of enrolled subjects, limited sample
      sizes and uncertainties regarding optimal mechanisms of delivering therapy.
      Despite initial reports which suggested limited benefit to hepatic artery
      embolization-based treatment, more recently published, well-conducted studies
      demonstrate a survival benefit conferred by hepatic artery chemoembolization.
      Chemoembolization likely confers a benefit greater than that associated with
      embolization without chemical agents. There is limited evidence and consensus
      regarding optimal choice and dosage of chemical agents utilized for hepatic
      artery chemoembolization.

PMID- 15166617
TI  - Therapy for unresectable hepatocellular carcinoma: review of the randomized
      clinical trials-II: systemic and local non-embolization-based therapies in
      unresectable and advanced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is not only common, but often presents at a stage
      when potentially curative therapies are not feasible. Although hepatic artery
      chemoembolization likely confers survival benefit in unresectable HCC, the
      associated toxicities are substantial and warrant investigation of more
      efficacious and safe therapies. Many patients who present with unresectable HCC
      are not chemoembolization candidates, either because of extensive disease or
      severely impaired hepatic function. We reviewed 44 randomized trials
      investigating non-embolization-based therapies in unresectable HCC. Hepatic
      artery infusion of [I]lipiodol appears safe; initial studies suggest a survival
      benefit and efficacy comparable to more toxic embolization-based therapies. Some
      cytotoxic chemotherapy may confer a modest survival benefit in advanced HCC
      (including oral fluoropyrimidines, and hepatic arterial or i.v. cisplatin and
      doxorubicin). Tamoxifen does not confer survival benefit, either in advanced or
      limited HCC. Other therapies warranting further study include interferon (in
      optimally cytoreduced HCC), megestrol in patients with variant estrogen
      receptors, octreotide and pravastatin. More adequately powered, rigorously
      conducted studies will hopefully identify useful chemo-, radio-, immuno-,
      embolization-based and biologically targeted therapies during the next decade.

PMID- 15166619
TI  - Acute lung injury as an adverse event of gefitinib.
AB  - Gefitinib, a selective epidermal growth factor receptor tyrosine kinase
      inhibitor, is an effective treatment for patients with non-small cell lung cancer
      (NSCLC). Some investigators have recently reported several patients complicated
      by acute lung injury after the initiation of gefitinib administration. In this
      report, we investigated the efficacy and adverse events during treatment with
      gefitinib. The subjects of this study were all of the 110 patients with NSCLC who
      were treated in our hospital and its eight branch hospitals. Patients received
      gefitinib at a dose of 250 mg once daily. The response rate was 30%. The
      frequently reported adverse events were skin disorders, gastrointestinal
      disturbances, liver dysfunction and acute lung injury. Five of the 12 patients
      who were considered to have suffered acute lung injury died of progressive
      respiratory failure. Of the nine patients who had pulmonary fibrosis before use
      of gefitinib, five developed acute lung injury during the treatment. Sera from
      three of the 12 patients were evaluated and all three showed increases of
      surfactant protein (SP)-A, SP-D and KL-6. We conclude that gefitinib was
      clinically useful. However, several patients suffered acute lung injury which
      could have been caused by gefitinib. A detection system including SP-A, SP-D and
      KL-6 as prime candidates as markers should be established as promptly as
      possible. Clinicians should be aware that treatment of NSCLC with gefitinib
      involves the risk of acute lung injury and therefore careful consideration should
      be given before deciding whether or not gefitinib is indicated for treatment.
      Further study is necessary to elucidate the mechanism of acute lung injury by
      gefitinib.

PMID- 15166618
TI  - Intraindividual variability in busulfan pharmacokinetics in patients undergoing a
      bone marrow transplant: assessment of a test dose and first dose strategy.
AB  - Busulfan systemic exposure correlates with regimen-related toxicity, engraftment
      and relapse in select patients receiving high-dose oral busulfan (HD-BU) (1 mg/kg
      dose or 40 mg/m dose every 6 h for 16 doses) as part of a preparative regimen for
      bone marrow transplantation. Therapeutic drug monitoring is frequently conducted
      after the first HD-BU dose in order to determine necessary dose adjustments.
      Limitations with this method include the need for rapid determination of busulfan
      plasma concentration and difficulties with estimating apparent oral clearance in
      patients who exhibit delayed absorption of HD-BU. This pharmacokinetic study was
      conducted to evaluate the ability of the apparent oral clearance obtained after
      administering a lower (0.25 mg/kg) test dose and the traditional (1 mg/kg) first
      dose to predict the dose required to achieve a desired area under the
      concentration-time curve (AUC) at steady-state (13th dose). In addition, the
      pharmacokinetic parameters of test, first and 13th dose were compared to assess
      intrasubject variability. Twenty-nine patients received a test dose of oral
      busulfan (0.25 mg/kg) the day immediately prior to initiation of HD-BU. Busulfan
      serum concentrations were measured following the test, first and 13th doses using
      gas chromatography with electron capture detection. The AUC and apparent oral
      clearance were calculated using non-compartmental analysis. Therapeutic drug
      monitoring following the first dose of HD-BU was conducted for clinical purposes
      in six patients, and dose adjustment between the first and 13th dose occurred in
      only two patients. The dose-corrected test dose and first dose AUC and apparent
      oral clearance were not bioequivalent (two one-sided t-tests, +/-20%). The first
      dose and 13th dose AUC and apparent oral clearance were also not bioequivalent.
      Six of the 29 patients receiving HD-BU dose based on weight (1 mg/kg) would have
      achieved a steady-state AUC of 3600-5400 ng x h/ml, a frequently used target AUC,
      as compared to eight and 13 patients if their dose was based on the apparent oral
      clearance following the test dose and first dose HD-BU, respectively. Monitoring
      busulfan concentrations after a test dose or a first dose provides a better
      estimate of the dose needed to achieve the target steady-state AUC as compared to
      traditional weight-based dosing. However, significant intraindividual variability
      exists in the apparent oral clearance of busulfan and follow-up therapeutic drug
      monitoring is recommended particularly if the desired target AUC range is narrow.

PMID- 15166620
TI  - Phase I study of the combination of oxaliplatin, irinotecan and continuous
      infusion 5-fluorouracil in digestive tumors.
AB  - Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown
      their efficacy in metastatic colorectal cancer. The synergism of these drugs has
      been demonstrated in vivo and in vitro. The aim of this study was to determine
      the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a
      further phase II study. Eighteen patients received the study treatment in four
      dose levels. The male:female ratio was 15:3 and the median age was 51.6 years
      (range 30-71). The type of tumor was colon in eight patients, rectum in four and
      other locations in six patients. The treatment was repeated every 2 weeks, at the
      fixed dose of L-OHP, 85 mg/m, and escalated doses of CPT-11 and 48-h infusion 5
      FU of 100/2000, 100/2250, 125/2250 and 150/2250 mg/m. Only one previous treatment
      for the advanced disease was permitted. Patients received a median of 8 cycles
      (range 1-26) and a total of 152 cycles were administered. Dose intensity
      administered at dose level L-OHP 85 mg/m, CPT-11 150 mg/m and 5-FU 2250 mg/m was
      95, 92 and 95% for L-OHP, CPT-11 and 5-FU, respectively. One patient in level 2
      and one patient in level 4 presented dose-limiting toxicity that was not
      confirmed in the three required additional patients by level. The anti-tumor
      activity was assessed in nine patients: seven partial responses, one stable
      disease and one progressive disease. The maximum-tolerated dose was not reached,
      and thus the recommended dose for this combination schedule is L-OHP, 85 mg/m,
      CPT-11, 150 mg/m and 5-FU, 2250 mg/m 48-h continuous infusion, the same doses
      that were recommended for the drugs when administered in combination therapy of L
      OHP + 5-FU or CPT-11 + 5-FU. A phase II study in first-line treatment of patients
      with metastatic colorectal cancer with this dose regimen is ongoing.

PMID- 15166621
TI  - Prospective multicenter phase II study of irinotecan as third-line therapy in
      metastatic colorectal cancer and progression after bolus and infusional 5
      fluorouracil.
AB  - Irinotecan has proven anti-tumor activity as induction treatment in combination
      with 5-fluorouracil (5-FU) or as second-line treatment after 5-FU in patients
      with metastatic colorectal cancer. The aim of the present phase II study was to
      evaluate irinotecan as third-line chemotherapy in patients with colorectal cancer
      after sequential treatment with bolus 5-FU followed by an infusional 5-FU
      regimen. Patients pretreated with bolus 5-FU/folinic acid and the infusional 5
      FU/folinic acid regimen were treated with 350 mg/m irinotecan i.v. once every 3
      weeks in a multicenter phase II study. Tumor size was measured every cycle and
      treatment with irinotecan was continued until the occurrence of progressive
      disease or unacceptable toxicity. A total of 50 pretreated patients were
      included. Of the 45 evaluable patients, 13.3% [n=6, 95% confidence interval (CI)
      5.1-26.8] attained a response (complete/partial response) to treatment lasting
      5.6 months (95% CI 4.2-6.3) and in four patients response has been confirmed
      (8.9%, 95% CI 2.5-21.2). Disease stabilization was noted in 51.1% of the patients
      (n=23, 95% CI 35.8-66.3). The median duration of response/disease stabilization
      was 4.2 months (95% CI 3.2-6.0). Median overall survival was 7.9 months (95% CI
      6.1-11.1), corresponding to a calculated 1-year survival of 28.3% (95% CI 15.2
      41.3). Severe neutropenia occurred in 14% (n=7) and anemia grade III in 6% of the
      patients (n=3). The most frequent non-hematological toxicity grade III/IV related
      to treatment was diarrhea in 24% of the patients (n=12), followed by vomiting in
      8% (n=4) and constipation as well as infection in two patients each (4%)
      (evaluable n=50). We conclude single-agent irinotecan is an effective and well
      tolerable treatment in pretreated patients with metastatic colorectal cancer
      after failure of bolus and infusional 5-FU/folinic acid regimens. Elderly
      patients had the same probability to respond.

PMID- 15166622
TI  - Pegylated liposomal doxorubicin hydrochloride (PLD) and paclitaxel in recurrent
      or metastatic head and neck carcinoma: a phase I/II study conducted by the
      Hellenic Cooperative Oncology Group (HeCOG).
AB  - A phase I pharmacokinetics and dose-finding study and a phase II study of the
      combination of pegylated liposomal doxorubicin HCl (PLD) and paclitaxel were
      conducted in patients with recurrent or metastatic head and neck cancer (HNC).
      Sixty patients with recurrent or metastatic disease were enrolled in the study:
      11 patients in the phase I study and 49 patients in the phase II study. In the
      phase I study, the initial dose level of PLD was 35 mg/m as a 1-h infusion with
      escalating increments of 5 mg/m until the maximum tolerated dose (MTD) was
      reached. A fixed dose of paclitaxel (175 mg/m) was administered as a 3-h
      infusion. The combination was administered every 28 days. Pharmacokinetic studies
      performed on 10 patients indicated that the sequence of drug administration did
      not cause clinically significant modifications in the pharmacokinetics of either
      drug. The MTD for PLD was 45 mg/m (dose level 3) and the dose-limiting toxicity
      was febrile neutropenia, occurring in three of five patients. The phase II dose
      of PLD was 40 mg/m (dose level 2) and a total of 214 cycles were delivered. Grade
      3 or 4 neutropenia was observed in 26% patients and febrile neutropenia occurred
      in 16% of patients. Grade 3 palmar-plantar erythrodysesthesia (PPE) was recorded
      in only one patient. The overall response rate was 28% for patients with non
      nasopharyngeal tumors [95% confidence interval (CI) 15-45%] and 28.6% for the
      study population (95% CI 17-43%). The median survival for the study population
      was 9.7 months; 1-year survival was 38%. We conclude that the recommended dose
      for the combination of PLD and paclitaxel is 40 and 175 mg/m every 28 days,
      without granulocyte colony stimulating factor support. The combination of
      paclitaxel with PLD demonstrated activity in recurrent or metastatic HNC, a
      favorable toxicity profile and relative ease of administration.

PMID- 15166623
TI  - Biweekly docetaxel as second-line chemotherapy of patients with advanced non
      small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP
      006-00).
AB  - This phase II trial assessed the antitumoral activity and toxicity of docetaxel
      50 mg/m (1-h i.v. infusion) administered every 2 weeks as second-line treatment
      in 45 patients with advanced non-small cell lung cancer (NSCLC). A total of 251
      infusions (median 4 per patient) were administered. The actual and relative
      median dose intensity values were 24.2 mg/m/week and 0.97, respectively. Thirty
      seven patients were evaluable for tumor response. The overall response rate was
      20% [95% confidence interval (CI) 8-32%] and included one complete response (2%)
      and eight partial responses (18%). Stable disease was found in seven patients
      (16%). With a median follow-up of 4 months, the median time to disease
      progression was 2.8 months (95% CI 1.9-3.7), the median overall survival was 4.0
      months (95% CI 3.4-4.6) and the 1-year survival rate was 23% (95% CI 9-37). The
      every-2-weeks docetaxel schedule was well tolerated. Grade 3/4 non-hematological
      toxicities showed rates of 5% or less of patients and 2% or less of cycles. The
      main grade 3/4 hematological toxicity was neutropenia (16% of patients and 8% of
      cycles). No febrile neutropenia was found. Nevertheless, one toxic death was
      reported. We conclude that the biweekly docetaxel schedule showed an antitumoral
      activity similar to that found with the every-3-weeks or weekly docetaxel
      schedule in a second-line setting for advanced NSCLC. This antitumoral effect was
      associated with a marked reduction in hematological toxicity, therefore
      suggesting that this new docetaxel schedule might be useful in the design of
      combined second-line schedules for treating NSCLC.

PMID- 15166624
TI  - Preliminary study on pharmacokinetics of dacarbazine and fotemustine in
      glioblastoma multiforme patients does not indicate gender-specific differences.
AB  - Twelve patients (six female and six male) with histologically proven glioblastoma
      multiforme were investigated during the administration of the first cycle of
      dacarbazine (D; 200 mg/m) and fotemustine (F; 100 mg/m). In total, 18 blood
      samples were collected for pharmacokinetic analysis (maximum plasma
      concentration, area under the concentration-time curve and total clearance) of D
      and F at 14 time points during therapy. D, its metabolite 5-aminoimidazole-4
      carboxamide and F were evaluated by reversed-phase HPLC. For statistical
      calculations, groups were compared by the non-parametric Wilcoxon test. p<0.05
      was considered statistically significant. No significant gender-dependent
      differences were observed in the pharmacokinetics of D and F. An additional
      response re-evaluation of 100 patients (50 female and 50 male) with glioblastoma
      multiforme, treated at our institution with D and F, gave no hint of any gender
      dependent different response rates. We conclude that there is no evidence,
      neither from pharmacokinetic nor from our clinical data, to consider different
      dosages of D and F in female and male patients with glioblastoma multiforme.

PMID- 15166625
TI  - Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx)
      in advanced solid cancers.
AB  - Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide
      exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve
      the activity of temozolomide. The rationale for investigating temozolomide plus
      Caelyx is based on their antitumor activity, their formulation and no significant
      overlapping toxicities. We conducted a study of a prolonged schedule of
      temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days.
      Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to
      four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients),
      DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6
      patients). Dose-limiting toxicities were noted after 2 or more cycles in one
      patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days).
      Treatment delays and/or dose reductions (due to hematological toxicity) were
      necessary in five of six patients receiving DL4 compared with one of six patients
      at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide
      125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4
      weeks). Other toxicities were mild. Antitumor activity was observed in eight
      patients, including one complete response (melanoma), three partial responses
      (one melanoma, two sarcomas) and four patients with stable disease (three
      melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma
      patients showed tumor stabilization in non-irradiated cerebral lesions. This
      schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks)
      compared to the standard 5-day regimen (1000 mg/m in the same amount of time).

PMID- 15166626
TI  - Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in
      human non-small cell lung cancer tumor xenograft models.
AB  - Our objective was the preclinical assessment of the pharmacokinetics, monotherapy
      and combined antitumor activity of the epidermal growth factor receptor
      (HER1/EGFR) tyrosine kinase inhibitor erlotinib in athymic nude mice bearing non
      small cell lung cancer (NSCLC) xenograft models. Immunohistochemistry determined
      the HER1/EGFR status of the NSCLC tumor models. Pharmacokinetic studies assessed
      plasma drug concentrations of erlotinib in tumor- and non-tumor-bearing athymic
      nude mice. These were followed by maximum tolerated dose (MTD) studies for
      erlotinib and each chemotherapy. Erlotinib was then assessed alone and in
      combination with these chemotherapies in the NSCLC xenograft models. Complete
      necropsies were performed on most of the animals in each study to further assess
      antitumor or toxic effects. Erlotinib monotherapy dose-dependently inhibited
      tumor growth in the H460a tumor model, correlating with circulating levels of
      drug. There was antitumor activity at the MTD with each agent tested in both the
      H460a and A549 tumor models (erlotinib 100 mg/kg: 71 and 93% tumor growth
      inhibition; gemcitabine 120 mg/kg: 93 and 75% tumor growth inhibition; cisplatin
      6 mg/kg: 81 and 88% tumor growth inhibition). When each compound was given at a
      fraction of the MTD, tumor growth inhibition was suboptimal. Combinations of
      gemcitabine or cisplatin with erlotinib were assessed at 25% of the MTD to
      determine efficacy. In both NSCLC models, doses of gemcitabine (30 mg/kg) or
      cisplatin (1.5 mg/kg) with erlotinib (25 mg/kg) at 25% of the MTD were well
      tolerated. For the slow growing A549 tumor, there was significant tumor growth
      inhibition in the gemcitabine/erlotinib and cisplatin/erlotinib combinations
      (above 100 and 98%, respectively), with partial regressions. For the faster
      growing H460a tumor, there was significant but less remarkable tumor growth
      inhibition in these same combinations (86 and 53% respectively). These results
      show that in NSCLC xenograft tumors with similar levels of EGFR expression, the
      antitumor activity of erlotinib is robust both as monotherapy and in combination
      with chemotherapies.

PMID- 15166627
TI  - Multisite inhibition by phenylacetate of PC-3 cell growth.
AB  - Phenylacetate (PA) is a reversible inhibitor of tumor cell growth and an
      inhibitor of mevalonate pyrophosphate decarboxylase (MPD). We hypothesized that
      MPD inhibition should lower rates of protein accumulation and accretion of cell
      number in all cell lines regardless of tumorigenic status or origin of the cell
      lines. PA treatment inhibited growth of MCF-7, NIH-3T3, Detroit 551, UT-2, NCTC
      929, COS-1 and PC-3 cell lines. NCTC-929 cells lack cadherins and Cos-1 cells are
      deficient in PPARalpha and PPARgamma, proteins suggested to be central to the
      action of PA. Oxidative metabolism was not impeded by PA treatment. One
      dimensional and two-dimensional FACS analysis of BrdU incorporation failed to
      demonstrate a redistribution of nuclei in the cell cycle or that the rate of
      cells entering S phase had changed. Time-lapse photo-microscopy studies reveal a
      process that left condensed nuclei with little or no cytoplasm. However, negative
      TUNEL assay results and failure to block cell loss with z-VAD-fmk suggest this
      type of cell death is not typical apoptosis, but cell death is responsible for
      the lower rates of cell and protein accumulation. Supplementation studies with
      mevalonate pathway intermediates during inhibition of the mevalonate pathway of
      cholesterol biosynthesis by lovastatin confirmed MPD as a site of PA inhibition
      of growth, but in the presence of lovastatin with or without farnesyl
      pyrophosphate plus geranylgeranyl pyrophosphate, additive inhibition by PA
      revealed additional site(s). The existence of site(s) in addition to MPD suggests
      effective PA-based agents might be developed that would not inhibit MPD.

PMID- 15166628
TI  - Cholesteryl butyrate solid lipid nanoparticles as a butyric acid pro-drug:
      effects on cell proliferation, cell-cycle distribution and c-myc expression in
      human leukemic cells.
AB  - Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed
      as a pro-drug to deliver butyric acid. We compared the effects on cell growth,
      cell-cycle distribution and c-myc expression of chol-but SLN and sodium butyrate
      (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell
      lines 0.5 and 1.0 mM chol-but SLN provoked a complete block of cell growth. Cell
      cycle analysis demonstrated in Jurkat cells that 0.25 mM chol-but SLN caused a
      pronounced increase of G2/M cells and a decrease of G0/G1 cells, whereas in U937
      and HL-60 cells chol-but SLN led to a dose-dependent increase of G0/G1 cells,
      with a decrease of G2/M cells. In Jurkat and HL-60 cells 0.5 mM chol-but SLN
      induced a significant increase of sub-G0/G1 apoptotic cells. Cell growth and cell
      cycle distribution were unaffected by the same concentrations of Na-but. A
      concentration of 0.25 mM chol-but SLN was able to cause a rapid and transient
      down-regulation of c-myc expression in all the cell lines, whereas 1 mM Na-but
      caused a slight reduction of c-myc expression only in U937 cells. The results
      show how chol-but SLN affects the proliferation pattern of both myeloid and
      lymphoid cells to an extent greater than the natural butyrate.

PMID- 15166630
TI  - Alcohol and Suicidal Behavior. Proceedings of a workshop. Bethesda, Maryland,
      USA, March 21-22, 2002.

PMID- 15166629
TI  - New platinum(IV) complex with adamantylamine ligand as a promising anti-cancer
      drug: comparison of in vitro cytotoxic potential towards A2780/cisR cisplatin
      resistant cell line within homologous series of platinum(IV) complexes.
AB  - The aim of this study was to compare anti-tumor potency of platinum(IV) complexes
      with increasing hydrophobicity of their ligands. Cytotoxic potential of the new
      platinum(IV) complex, coded as LA-12 [(OC-6-43)-bis(acetato)(1
      adamantylamine)amminedichloroplatinum(IV)], was compared within the series of
      complexes of the general formula (OC-6-43)
      bis(acetato)(alkylamine)amminedichloroplatinum(IV). Alkylamine ligands with
      increasing hydrophobicity were: isopropylamine, cyclohexylamine, 1-adamantylamine
      and 3,5-dimethyl-1-adamantylamine. Particular platinum(IV) complexes were coded
      as LA-4, LA-2 (known as JM-216), LA-12 and LA-15, respectively. Cytotoxicity was
      tested with the microplate tetrazolium (MTT) assay on the panel of cancer cell
      lines and the results were verified by microscopy. HPLC was used to measure
      hydrophobicity, stability of complexes in various buffers and velocity constants
      for their reactivity with glutathione. Platinum(IV) complexes with bulky
      hydrophobic ligands (LA-12 and LA-15) demonstrated about one order higher
      velocity constant for pseudo-first-order reaction with glutathione in comparison
      to cisplatin, LA-4 and LA-2, whose velocity constants were close to those
      measured for cisplatin and related platinum(II) complexes. Cytotoxicities of LA
      12 and LA-15 towards cisplatin-resistant epithelial carcinoma A2780/cisR were
      superior to cisplatin, LA-4 and LA-2 in both 24- and 72-h continuous exposure MTT
      tests. Rapid induction of apoptosis in the treated cancer cell lines and no
      cisplatin cross-resistance were found for LA-12, which is a candidate for
      clinical testing.

PMID- 15166631
TI  - Alcohol and suicidal behavior: overview of a research workshop.

PMID- 15166632
TI  - Predisposing and precipitating factors for suicide among alcoholics: empirical
      review and conceptual integration.
AB  - Alcohol dependence is a potent risk factor for suicide. Accordingly, alcoholics
      should be targeted in suicide prevention efforts. This article reviews the
      literature on suicide among alcoholics and provides a model that may inform
      research, clinical work, and prevention efforts. In this model, we propose that
      aggression/impulsivity, severe alcoholism, negative affect, and hopelessness are
      key predisposing factors for suicide among alcoholics. We propose that major
      depressive episodes and stressful life events, particularly interpersonal
      difficulties, are key precipitating factors. We also integrate these constructs
      in a model that proposes that many acts of suicide among alcoholics may be viewed
      as acts of reactive aggression executed in the midst of distress over a lost or
      threatened relationship. Empirical evidence for the model is discussed along with
      its limitations. The next generation of research on alcoholism and suicide should
      include a focus on the interpersonal anlage of suicide in this population.

PMID- 15166633
TI  - Acute alcohol use and suicidal behavior: a review of the literature.
AB  - BACKGROUND: Both acute and chronic use of alcohol are associated with suicidal
      behavior. However, the differing relationship of each component of alcohol use
      and possible causal mechanisms remain unclear. METHODS: This article reviews and
      summarizes associations between acute alcohol consumption (with and without
      intoxication) and suicidal behavior (both completed suicide and suicide attempts)
      among adults 19 years and older, as presented in literature published between
      1991 and 2001. Possible mechanisms and methodologic challenges for evaluating the
      association are also discussed. An application of a research design (the case
      crossover study) that has the potential for addressing the effects of acute
      alcohol use over and above usual or chronic use is presented. RESULTS: The
      majority of articles reviewed were restricted to descriptive studies that
      documented the prevalence of suicide completers or attempters who tested positive
      for alcohol use. A wide range of alcohol-positive cases were found for both
      completed suicide (10-69%) and suicide attempts (10-73%). Common methodologic
      limitations included the lack of control groups (for evaluating risk conferred by
      alcohol use), selection and ascertainment bias, and small sample sizes. The
      results of the case-crossover pilot study indicated substantially higher risk of
      suicide during or shortly after use of alcohol compared with alcohol-free
      periods. CONCLUSIONS: Although there is a substantial literature of published
      studies on acute alcohol use and suicidal behavior, the majority of studies focus
      on completed suicide and report prevalence estimates. Findings from such studies
      are subject to several possible sources of bias and have not advanced our
      knowledge of mechanisms in the association between acute alcohol use and suicidal
      behavior. The case-crossover design may help to overcome some limitations of
      these studies and facilitate evaluation of associations and possible causal
      mechanisms by which acute alcohol use is linked to suicidal behavior.

PMID- 15166634
TI  - Suicidal behaviors and alcohol use among adolescents: a developmental
      psychopathology perspective.
AB  - A developmental psychopathology conceptual model was provided to represent the
      major categories of risk and protective factors, including alcohol use and binge
      drinking, that predict suicidal behaviors that range from suicidal thoughts to
      completed suicides. The conceptual model emphasized the importance of identifying
      age-specific sets of risk and protective factors to facilitate the development of
      effective interventions. As an empirical illustration, a multivariate mediation
      path model was specified and evaluated with a sample of teens. Findings indicated
      that several distal variables (e.g., difficult temperament, coping motives for
      drinking, lower family support, higher percentage of friends using alcohol)
      significantly predicted mediators (e.g., depression, stressful events, binge
      drinking) that, in turn, predicted suicidal behaviors. Binge drinking
      significantly predicted suicide attempts over and above the influence of
      depression and stressful events.

PMID- 15166635
TI  - Alcohol use and suicidal behavior in women: longitudinal patterns in a U.S.
      national sample.
AB  - BACKGROUND: Much of the research on suicidality has focused on adolescents and
      completed suicides, with less attention to types of suicidal behavior (ideation
      and attempts) that are more common among women. Research has associated women's
      suicidality with hazardous drinking, adverse childhood experiences, relationship
      problems, depression, and earlier suicidal behavior. The longitudinal analyses
      here examine long-term antecedents of suicidal ideation among women in the U.S.
      general population. METHODS: We used 1981 and 1991 survey data to predict post
      1991 suicidal ideation in a 1996 national sample of 709 women aged 26 to 54 (538
      current drinkers). Predictors included 1991 measures of hazardous drinking,
      depressive episodes, illicit drug use, general health, children at home,
      interaction with partner, and previous suicidal ideation. Predictors from
      childhood included recalled parental drinking, parental love or rejection, early
      drinking and sexual intercourse, and sexual abuse. Demographic predictors
      included age, education, and ethnicity. A three-stage structural equation model
      that included these variables was evaluated with Mplus for women who were
      drinkers in 1991 and/or 1996. RESULTS: Almost all women who attempted suicide
      also reported suicidal ideation. Among women drinkers, suicidal ideation before
      1991 was more common in the following groups: Latinas, women who believed that
      their parents had rejected them, and women who reported childhood sexual abuse.
      Hazardous drinking and poorer health in 1991, childhood histories of sexual abuse
      and early drinking, and previous suicidal ideation predicted suicidal ideation
      after 1991. Domestic stressors in 1991 (inability to share feelings with a
      partner and having four or more young children at home) also predicted subsequent
      suicidal ideation, but depressive episodes did not. Suicidal ideation was less
      likely among women drinkers who reported past illicit drug use. CONCLUSIONS:
      Suicidal ideation among women drinkers was largely predictable from previous
      suicidal ideation, hazardous drinking, adverse childhood experiences, and
      domestic stressors. Higher rates of pre-1991 suicidal ideation among Latinas
      indicate a need for further study of ethnic influences on suicidality. Reduced
      suicidal ideation among women with past illicit drug use suggests that
      conclusions about such use from shorter-term studies may be oversimplified.
      Understanding women's suicidal ideation, as a precursor to suicidal actions,
      requires more detailed research on pathways by which hazardous drinking as well
      as combined distress from childhood experiences and adult domestic environments
      may increase women's despair and thoughts of suicide.

PMID- 15166636
TI  - Role of alcohol in late-life suicide.
AB  - Suicide is among the leading causes of death in the United States, ranking 10th
      to 12th annually, depending on the year. Rates of suicide increase markedly among
      Americans over age 75, especially among white men. After age 85, rates are >5
      fold higher in this group than in the general population. The relationship
      between alcohol use and later-life suicide is complex and currently ill defined.
      Substance use disorders, particularly alcohol abuse and dependence, are the
      second most common category of axis I disorders associated with completed suicide
      among adults aged 65 and older, following only depression. The co-occurrence of
      alcohol use disorders and depression heightens suicide risk. Most studies that
      have evaluated the effects of alcohol in geriatric suicide have focused on older
      adults who met DSM criteria for abuse and/or dependence. However, the majority of
      older adults who are experiencing problems related to their alcohol use do not
      meet alcohol abuse/dependence criteria. Therefore, the role of at-risk and
      problem alcohol use in geriatric suicide may be underestimated. Drinking among
      elders elevates suicide risk through interactions with other factors that are
      more prevalent in this age group, such as depressive symptoms, medical illness,
      negatively perceived health status, and low social support. This article reviews
      the literature related to alcohol use and suicide among older adults. Clinical
      and research recommendations for addressing this problem are also presented.

PMID- 15166637
TI  - Serotonergic and noradrenergic neurobiology of alcoholic suicide.
AB  - BACKGROUND: Alcoholism is associated with alterations in the serotonergic and
      noradrenergic systems. Alcoholics are at a significantly higher risk for suicide
      than the general population. Altered serotonin (5-HT) function is associated with
      suicide and serious suicide attempts. We hypothesized patterns of abnormality
      associated independently with suicide and with alcoholism. METHODS: Quantitative
      autoradiographic experiments were performed in human postmortem brain tissue
      sections from alcoholics, alcoholic-suicide decedents, nonalcoholic suicide
      decedents, and normal controls diagnosed by psychological autopsy. RESULTS:
      Binding to 5-HT1A receptors is lower in both alcoholic suicides and alcoholic
      nonsuicides, suggesting that this effect is related to alcoholism and not
      suicide. In nonalcoholic suicides, there is a localized increase in 5-HT1A
      binding in ventral prefrontal cortex, hypothesized to be a response to less
      serotonin input. Therefore, alcoholic suicides may fail to up-regulate ventral
      prefrontal 5-HT1A receptors in response to decreased serotonergic transmission,
      failing to mitigate the impact of less serotonin upon signal transduction and
      thereby increasing the risk of suicidal behavior. Binding to the serotonin
      transporter is low in alcoholic suicides but not in alcoholic nonsuicides,
      suggesting an association with suicide, as nonalcoholic suicides also have
      decreased binding compared with controls. Evidence of impaired serotonergic
      innervation associated with alcoholism is also manifested by less 5-HT1D terminal
      autoreceptor binding in alcoholics. Nonalcoholic suicides do not have lower 5
      HT1D binding. In the noradrenergic system, alcoholics (suicide and nonsuicide)
      and nonalcoholic suicide victims all have fewer pigmented locus ceruleus neurons
      compared with controls, yet beta1-adrenergic binding is low in both alcoholic
      groups, whereas alpha1-and alpha2-adrenergic binding decreases are more
      pronounced in the alcoholic suicide group. These noradrenergic findings differ
      from those in nonalcoholic suicides, which have a common feature with alcoholics
      in having less alpha2-and beta1-adrenergic binding but more alpha1-adrenergic
      binding in ventrolateral and orbital cortex. CONCLUSION: Extensive but different
      abnormalities in both the serotonergic and noradrenergic systems have been
      identified in alcoholics and suicides, suggesting two separate patterns: one
      related to alcoholism and the other related to suicide. The different patterns
      suggest different causes and homeostatic responses for alcoholism and suicide.

PMID- 15166638
TI  - The search for genetic risk factors associated with suicidal behavior.
AB  - BACKGROUND: Suicide and suicidal behavior are prevalent among individuals with
      psychiatric disorders, including alcohol dependence. A genome screen was
      performed in multiplex alcohol dependent families ascertained as part of the
      Collaborative Study on the Genetics of Alcoholism to identify chromosomal regions
      of interest related to two types of suicidal behavior: suicide attempts and
      suicidality. METHODS: Sibling pair analyses were used to conduct linkage analyses
      using both qualitative and quantitative suicide-related phenotypes. The
      qualitative trait of "suicide attempts" was examined using 59 affected sibling
      pairs. The quantitative trait of "suicidality" was examined using all possible
      1366 sibling pairs and 705 independent sibling pairs. RESULTS: For the
      qualitative phenotype suicide attempts, chromosome 2 yielded a maximum lod score
      of 4.2. For the quantitative suicidality index, a maximum lod score of 1.8 was
      observed on chromosome 3, and a lod score of 1.5 was found on chromosome 1.
      CONCLUSIONS: This study represents the first genome-wide scan of suicidal
      behavior. Significant evidence of linkage was found on chromosome 2 for the
      phenotype suicide attempts, the same chromosomal region previously reported to be
      linked to alcohol dependence in this sample. This finding does not seem to be due
      solely to an association between suicide and alcohol dependence. There was more
      modest evidence of linkage to chromosomes 1 and 3 for suicidality; however, these
      findings did not reach statistical significance. There was no overlap in findings
      for these two phenotypes of suicidal behavior.

PMID- 15166639
TI  - Adolescent substance use and suicidal behavior: a review with implications for
      treatment research.
AB  - Adolescent substance use (alcohol and other drugs) and suicidal behavior,
      independently, pose serious public health problems. Youths who report co
      occurring substance use and suicidality are a particularly high-risk group. In
      this review, we explore four areas that are pertinent to research with substance
      abusing and suicidal adolescent populations. First, we review epidemiological
      research that is relevant to the association between substance use and suicidal
      behavior. Results suggest that substance use heightens statistical risk for
      suicidal behavior in adolescent clinical and community populations. Alcohol
      intoxication may serve as a proximal risk factor for suicidal behavior among
      distressed youths through its psychopharmacological effects on the brain.
      Substance use may also serve as a distal risk factor for suicidal behavior by
      increasing stress and exacerbating co-occurring psychopathology. Second, we
      propose different theoretical models that might explain the high rates of co
      occurring substance use and suicidal behavior among adolescents. Substance use
      may stem from an underlying syndrome of problem behavior among impulsive suicide
      attempters with predominant externalizing symptoms. In contrast, nonimpulsive
      suicide attempters with predominant internalizing symptoms may use substances to
      cope with negative affective states. Third, we explore the status of treatment
      research with substance abusing and suicidal adolescent populations. Studies of
      substance abuse treatment and suicidal behavior have neither adequately assessed
      nor incorporated treatment of the other co-occurring problem. Finally, we
      conclude with proposed directions for future research, including the development
      of integrated interventions tailored to adolescents with these co-occurring
      problems.

PMID- 15166640
TI  - Interventions in suicidal alcoholics.
AB  - Research involving suicidal alcoholics is scarce despite the frequent presence of
      suicidal ideation and behavior among alcoholics. Unfortunately, suicidal ideation
      is a common exclusion criterion from participation in most studies that are
      relevant to this population. This article addresses identifying, evaluating, and
      treating people with alcohol abuse or dependence who display suicidal ideation or
      suicidal behavior. The state of the art is reviewed regarding interventions,
      including acute stabilization and specific medications for alcoholism and
      depression with a special focus on the selective serotonin reuptake inhibitors.
      Appropriate hospitalization, discharge, and family involvement are discussed.
      Finally, gaps in knowledge are identified with a focus on priorities and
      directions for future research.

PMID- 15166641
TI  - Acoustic startle reactivity during acute alcohol withdrawal in rats that differ
      in genetic predisposition toward alcohol drinking: effect of stimulus
      characteristics.
AB  - BACKGROUND: We have previously reported an association between greater alcohol
      withdrawal magnitude after a single alcohol exposure and a genetic predisposition
      toward low alcohol drinking in rats selectively bred for differences in alcohol
      intake when acoustic startle reactivity to a tone stimulus was used to index
      acute alcohol withdrawal. The purpose of this study was to examine whether the
      quality of the acoustic startle stimulus (noise versus tone) is important for
      detecting a genetic relationship between alcohol withdrawal magnitude and alcohol
      drinking behavior. METHODS: Alcohol-naive male rats selectively bred for high
      alcohol intake [alcohol-preferring (P), high-alcohol-drinking (HAD)1, and HAD2]
      or low alcohol intake [alcohol-nonpreferring (NP), low-alcohol-drinking (LAD)1,
      and LAD2] received a single intragastric infusion of water or alcohol (4.0 g/20.3
      ml/kg; 25% v/v), and acoustic startle test sessions were given at 14, 16, 18, 20,
      and 24 hr after infusion. Each test session consisted of a 5-min acclimation
      period followed by random presentation of various white noise stimuli (90, 100,
      110, and 120 dB.) RESULTS: Line differences in acoustic startle magnitude under
      control conditions were present in all three pairs of selectively bred lines; P
      rats showed a greater startle magnitude relative to NP rats, whereas both LAD
      lines showed a greater startle magnitude relative to both HAD lines. During
      alcohol withdrawal, the P, HAD1, and HAD2 lines showed enhanced startle magnitude
      compared with their water-treated controls. No change in startle magnitude during
      alcohol withdrawal was found in the NP, LAD1, or LAD2 lines. CONCLUSIONS: In
      contrast to our prior findings, these results showed a genetic association
      between high alcohol drinking and a greater startle response magnitude to a noise
      stimulus during alcohol withdrawal. It seems that the genetic association between
      alcohol drinking and alcohol withdrawal, as assessed by the acoustic startle
      response, depends on the quality of the acoustic startle stimulus.

PMID- 15166642
TI  - Single-channel analyses of ethanol modulation of neuronal nicotinic acetylcholine
      receptors.
AB  - BACKGROUND: We have previously reported that ethanol potentiates the
      acetylcholine-induced currents of the alpha4beta2 neuronal nicotinic
      acetylcholine receptors in rat cortical neurons and of those that are stably
      expressed in human embryonic kidney cells. The potentiation of the maximal
      currents evoked by high concentrations of acetylcholine suggests that ethanol
      affects the channel gating. METHODS: We performed single-channel patch-clamp
      experiments to elucidate the detailed mechanism of ethanol modulation of the
      alpha4beta2 receptor that is stably expressed in human embryonic kidney cells.
      RESULTS: At least two conductance states, 40.5 pS and 21.9 pS, were activated by
      acetylcholine. Acetylcholine at 30 nM predominantly induced the high conductance
      state currents (85% of total). Ethanol did not affect the single-channel
      conductance but selectively modulated the high-conductance state currents. The
      high-conductance state currents exhibited two open time constants. Both time
      constants were increased by 100 mM ethanol, from 1.9 msec to 2.8 msec and from
      9.0 msec to 15.5 msec, respectively. Ethanol also prolonged the burst duration
      and the open time within burst and increased the probability of channel opening.
      CONCLUSIONS: These changes in single-channel parameters indicate that ethanol
      stabilizes the alpha4beta2 receptor-channel in the opening state, explaining how
      the maximum acetylcholine-induced whole-cell currents are further potentiated by
      ethanol.

PMID- 15166643
TI  - Alcohol acutely down-regulates urea synthesis in normal men.
AB  - BACKGROUND: Human nitrogen balance studies suggest that alcohol up-regulates urea
      synthesis and promotes nitrogen catabolism, whereas animal studies conversely
      indicate that alcohol down-regulates urea synthesis, possibly via a redox effect.
      This study aimed to investigate the acute effects of alcohol exposure at a plasma
      concentration of about 10 mmol/liter on urea synthesis in healthy volunteers and
      to investigate whether methylene blue alleviates the effect of alcohol. METHODS:
      Eleven males were studied three times in a randomized sequence crossover design.
      They received either alanine infusion to control the rate of urea synthesis
      (control), alanine + alcohol, or alanine + alcohol + methylene blue. The
      substrate independent regulation of urea synthesis was studied by means of the
      functional hepatic nitrogen clearance, that is, the slope of the linear relation
      between blood amino nitrogen concentrations and rates of urea synthesis. RESULTS:
      Alcohol reduced functional hepatic nitrogen clearance to 37% and 51% during
      alcohol and alcohol + methylene blue infusion, respectively (p = 0.007).
      Accordingly, whole body nitrogen retention was higher during alcohol infusion.
      Glucagon, which up-regulates urea synthesis, increased during alcohol infusion.
      There was no change in insulin. Blood glucose was slightly lower at the end of
      the experiment when alcohol was infused. CONCLUSION: Low-dose infusion of alcohol
      acutely down-regulated urea synthesis in healthy volunteers, transiently favoring
      nitrogen preservation. The effect seemed not to depend on hormonal changes. It
      remains to be explored how the present results can be reconciled with the
      reported nitrogen wasting of chronic alcoholics.

PMID- 15166644
TI  - Long-lasting alterations of the mesolimbic dopamine system after periadolescent
      ethanol drinking by alcohol-preferring rats.
AB  - BACKGROUND: This study tested the hypothesis that ethanol consumption by alcohol
      preferring (P) rats during the periadolescent period causes persistent
      alterations in the mesolimbic dopamine (DA) system. After ethanol drinking during
      periadolescence, P rats were examined for alterations in basal locomotor
      activity, changes in extracellular DA levels and extraction fraction in the
      nucleus accumbens (NAc) by using no-net-flux (NNF) microdialysis, and changes in
      the response of the mesolimbic DA system to ethanol. METHODS: Male P rat pups
      were given 24-hr free-choice access to 15% (v/v) ethanol from postnatal day (PD)
      30 through PD 60. On PD 70, rats were assessed for locomotor activity. On PD 70
      to 80, rats were implanted with bilateral guide cannulas aimed above the NAc.
      After at least 5 days, microdialysis probes were inserted bilaterally; on the
      following day, NNF microdialysis experiments were conducted. On the day after the
      NNF experiment, conventional microdialysis experiments were conducted to measure
      extracellular levels of DA in response to intraperitoneal injection of saline or
      ethanol 2.5 g/kg. RESULTS: Compared with the ethanol-naive group, ethanol
      drinking by P rats during periadolescence did not alter basal locomotor activity,
      nor did it alter the basal extracellular concentration of DA. There was, however,
      a significant increase in the extraction fraction of DA of ethanol-drinking
      animals relative to the controls (57.4 +/- 2.7% and 45.8 +/- 2.3%, respectively).
      Additionally, compared with controls, P rats with exposure to ethanol during the
      periadolescent period showed a prolonged increase in the extracellular levels of
      DA after a challenge dose of ethanol. CONCLUSIONS: The results of the
      microdialysis experiments suggest that periadolescent ethanol drinking by P rats
      increases basal DA neurotransmission (as indicated by higher DA clearance while
      maintaining the same extracellular DA concentrations) and prolongs the response
      of DA neurotransmission to ethanol.

PMID- 15166645
TI  - Differential neurosensitivity to the discriminative stimulus properties of
      ethanol in C57BL/6J and C3H/He mice.
AB  - BACKGROUND: A large body of evidence suggests that the interoceptive cue
      associated with ethanol intoxication is complex and dependent on a number of
      environmental and biological factors. Despite the fact that mice have been widely
      used to study genetic influences on sensitivity to various actions of ethanol,
      few studies have used mice to examine sensitivity to the discriminative stimulus
      effects of ethanol. The purpose of this study was to compare sensitivity to the
      discriminative stimulus effects of ethanol in two inbred mouse strains, namely
      C57BL/6J and C3H/He mice. METHODS: Adult male C57BL/6J and C3H/He mice were
      trained to discriminate between ethanol and saline using a two-lever food
      reinforcement operant procedure. Once criterion discrimination performance was
      achieved, dose-response functions were determined from generalization tests.
      Additional experiments were conducted to determine whether differences in
      discrimination performance were related to differential blood/brain ethanol
      levels in the two mouse strains. RESULTS: A greater proportion of C57BL/6J mice
      acquired the discrimination and required fewer trials to achieve criterion
      performance compared with C3H/He mice with a 1.0 g/kg ethanol training dose. This
      deficit in acquisition was overcome when the training dose was increased to 2.0
      g/kg for C3H/He mice. In a second experiment, a 1.5 g/kg training dose of ethanol
      was used for both strains. Again, a greater proportion of C57BL/6J mice acquired
      the discrimination and required fewer training trials to achieve criterion
      performance compared with C3H/He mice. Blood ethanol levels did not differ
      between the strains after administration of the 1.5 g/kg training dose. However,
      blood and brain ethanol levels did differ between the strains after doses of
      ethanol were administered that produced equivalent discrimination performance.
      CONCLUSIONS: Results indicate that ethanol discrimination was more readily
      acquired and maintained in C57BL/6J mice than C3H/He mice. Ethanol dose-response
      functions generated from generalization tests also clearly demonstrated greater
      sensitivity to the discriminative stimulus properties of ethanol in C57BL/6J mice
      compared with the C3H/He strain. This differential sensitivity to the
      interoceptive cue produced by ethanol does not seem to be related to learning or
      pharmacokinetic differences between the two inbred strains.

PMID- 15166647
TI  - Alanine aminopeptidase activity in urine: a new marker of chronic alcohol abuse?
AB  - BACKGROUND: The purpose of this study was to evaluate the activity of urinary
      alanine aminopeptidase (AAP), the enzyme released from the brush border membranes
      of renal proximal tubules, as a new biological marker of chronic alcohol abuse.
      METHODS: The AAP activity was assayed and compared between a group of 76
      alcoholics undergoing detoxification and a group of 37 alcoholics abstaining from
      alcohol for at least 6 weeks. In all patients, the enzyme activity was measured
      both in untreated urine (uAAP) and after removal of endogenous AAP inhibitors by
      molecular filtration on Sephadex (eAAP). RESULTS: There was a correlation between
      the uAAP and eAAP activities in both groups of patients (r = 0.61 and r = 0.81 in
      abstinent alcoholics and in alcoholics undergoing detoxification, respectively),
      and both the uAAP activity and the eAAP activity were significantly and markedly
      higher in alcoholics being detoxified than in their abstinent counterparts. As
      revealed by receiver operating characteristic analysis, the discriminative power
      of the eAAP activity assay was higher than that of the uAAP activity assay. The
      area under the corresponding receiver operating characteristic curves was 0.84 +/
      0.04 and 0.78 +/- 0.05 (mean +/- SE), respectively. CONCLUSIONS: The results of
      this study demonstrate that the assays of urinary AAP activity, which relate to
      the nephrotoxic effects of alcohol abuse, could be a valuable complement to the
      other presently used markers of chronic alcohol abuse that are generally based on
      ethanol hepatotoxicity. Compared with the uAAP activity test, the eAAP activity
      test is of clear diagnostic advantage.

PMID- 15166646
TI  - DRD2 gene transfer into the nucleus accumbens core of the alcohol preferring and
      nonpreferring rats attenuates alcohol drinking.
AB  - BACKGROUND: Transient overexpression of the dopamine D2 receptor (DRD2) gene in
      the nucleus accumbens (NAc) using an adenoviral vector has been associated with a
      significant decrease in alcohol intake in Sprague Dawley rats. This
      overexpression of DRD2 reduced alcohol consumption in a two-bottle-choice
      paradigm and supported the view that high levels of DRD2 may be protective
      against alcohol abuse. METHODS: Using a limited access (1 hr) two-bottle-choice
      (water versus 10% ethanol) drinking paradigm, we examined the effects of the DRD2
      vector in alcohol intake in the genetically inbred alcohol-preferring (P) and 
      nonpreferring (NP) rats. In addition, micro-positron emission tomography imaging
      was used at the completion of the study to assess in vivo the chronic (7 weeks)
      effects of ethanol exposure on DRD2 levels between the two groups. RESULTS: P
      rats that were treated with the DRD2 vector (in the NAc) significantly attenuated
      their alcohol preference (37% decrease) and intake (48% decrease), and these
      measures returned to pretreatment levels by day 20. A similar pattern of behavior
      (attenuation of ethanol drinking) was observed in NP rats. Analysis of the
      [C]raclopride micro-positron emission tomography data after chronic (7 weeks)
      exposure to ethanol revealed clear DRD2 binding differences between the P and NP
      rats. P rats showed 16% lower [C]raclopride specific binding in striatum than the
      NP rats. CONCLUSIONS: These findings further support our hypothesis that high
      levels of DRD2 are causally associated with a reduction in alcohol consumption
      and may serve as a protective factor against alcoholism. That this effect was
      seen in P rats, which are predisposed to alcohol intake, suggests that they are
      protective even in those who are genetically predisposed to high alcohol intake.
      It is noteworthy that increasing DRD2 significantly decreased alcohol intake but
      did not abolish it, suggesting that high DRD2 levels may specifically interfere
      with the administration of large quantities of alcohol. The significantly higher
      DRD2 concentration in NP than P rats after 7 weeks of ethanol therefore could
      account for low alcohol intake.

PMID- 15166648
TI  - A double-blind, placebo-controlled study of olanzapine in the treatment of
      alcohol-dependence disorder.
AB  - BACKGROUND: A 12-week, double-blind, randomized, parallel-group clinical trial,
      comparing olanzapine and placebo treatment together with cognitive-behavioral
      psychotherapy, was carried out to determine the efficacy, safety, and
      tolerability of olanzapine in the treatment of alcoholism. METHODS: A total of 60
      alcohol-dependent patients were assigned to 12 weeks' treatment with either
      olanzapine or placebo. The primary variable relapse to heavy drinking rate was
      evaluated by means of intention-to-treat analyses. Alcohol consumption, craving,
      adverse events, and changes in the biochemical markers of heavy drinking and
      possible toxicity were also evaluated. RESULTS: We did not find significant
      differences in the survival analysis between placebo and olanzapine-treated
      patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%)
      patients treated with olanzapine relapsed compared with 9 (29%) of those
      receiving placebo (chi = 0.53, df = 1, p = 0.5). Although some adverse events
      (weight gain, increased appetite, drowsiness, constipation, and dry mouth) were
      found more frequently in the olanzapine group, differences did not reach
      statistical significance in comparison with the placebo group. CONCLUSIONS:
      Olanzapine was well tolerated, as the rate of adverse events was low, and it was
      safe, because it did not interfere with the normalization of biochemical markers
      of heavy drinking or alter liver function markers. Alcohol-dependent patients
      showed good adherence and compliance with the treatment protocol, but we found no
      differences in relapse rate or other drinking variables when comparing olanzapine
      with placebo-treated patients.

PMID- 15166649
TI  - Alcohol use disorders among emergency department-treated older adolescents: a new
      brief screen (RUFT-Cut) using the AUDIT, CAGE, CRAFFT, and RAPS-QF.
AB  - BACKGROUND: Early identification of alcohol use disorders (AUD) among emergency
      department (ED)-treated patients is important for facilitating intervention and
      further evaluation outside EDs. A number of brief screening instruments have been
      developed for identifying patients with AUD, but it is not clear whether they are
      practical and perform well with older adolescents in an ED setting. This study
      contrasted four brief screening instruments for detecting DSM-IV-defined AUD and
      tested a newly developed brief screen for use among ED-treated older adolescents.
      METHODS: The Alcohol Use Disorders Identification Test (AUDIT), the CAGE, the
      CRAFFT, and a modified RAPS-QF were given to 93 alcohol-using older adolescents
      (55% men; aged 18-20 years) in an ED. Receiver operator characteristic analyses
      were used to evaluate the performance of brief screens against the criterion of a
      lifetime DSM-IV alcohol abuse or dependence diagnosis. RESULTS: Of existing
      instruments, the AUDIT had the best overall performance in identifying AUD
      (sensitivity, 82%; specificity, 78%). A new, shorter screening instrument
      composed of two AUDIT items, two CRAFFT items, and one CAGE item (RUFT-Cut)
      performed as well as the AUDIT (sensitivity, 82%; specificity, 78%). CONCLUSIONS:
      Among existing alcohol screening instruments, the AUDIT performed best for
      identifying ED-treated older adolescents with alcohol use disorders. The RUFT-Cut
      is a brief screening instrument for AUD that shows promise for identifying ED
      treated older adolescents who are in need of intervention or further evaluation.
      Future research should focus on use of the RUFT-Cut in other settings with
      larger, more diverse samples of adolescents.

PMID- 15166650
TI  - Gender differences in the relationships between multiple measures of alcohol
      consumption and physical and mental health.
AB  - BACKGROUND: Epidemiological research examining health consequences of alcohol
      consumption generally relies on average volume consumed, yet examinations of
      drinking patterns show different dimensions of use associated with different
      health outcomes. Gender differences in metabolism and body composition may lead
      to gender-specific consequences of drinking frequency, quantity consumed per
      occasion, average amount consumed, and drinking pattern. Inconsistent results
      suggest gender differences are not well understood. METHODS: Participants were
      3069 male and 2600 female health maintenance organization survey respondents.
      Gender differences in relationships between alcohol consumption and health were
      examined using analyses of covariance adjusting for age alone and for age,
      ethnicity, marital status, body water index, and smoking. Past-year alcohol
      consumption (frequency, quantity per occasion, average drinks per month, and
      drinking pattern) and health measures (Short Form-36 general health, physical
      functioning, mental health subscales) were examined. RESULTS: Gender x drinking
      frequency and drinking quantity interactions were significant in age-adjusted and
      fully adjusted models of general health and physical functioning. Gender
      interactions for drinking pattern were significant in the age-adjusted model and
      marginally significant in the fully adjusted model. No gender x drinking measure
      interactions were found for mental health. Fully adjusted models attenuated but
      did not eliminate gender differences for health and magnified relationships for
      functioning, the latter after adjusting for body water. For both genders, light
      to moderate consumption and more frequent drinking were associated with better
      health and functioning; relationships were stronger among women than men.
      CONCLUSIONS: Gender x drinking measure interactions in health outcomes suggest
      analyses should include such interactions except, possibly, for mental health.
      Adjusting for potential confounders can attenuate (general health) or magnify
      (physical functioning) gender differences. Functional status appears a sensitive
      measure for evaluating gender differences in alcohol's health effects, adjusting
      for body water. Women's health may benefit proportionally more from moderate
      drinking than men's.

PMID- 15166651
TI  - Prenatal maternal alcohol consumption and hospitalization with asthma in
      childhood: a population-based follow-up study.
AB  - BACKGROUND: Asthma may have a prenatal origin. We examined whether maternal
      alcohol consumption during pregnancy increases the risk of hospitalization with
      asthma in children. METHODS: We conducted a follow-up study on 10,440 singletons
      born at approximately 36 weeks of gestation or later to mothers attending midwife
      centers between April 1984 and April 1987 in Denmark. The mothers completed a
      questionnaire regarding lifestyle and socioeconomic factors, including alcohol
      consumption. The children were followed up through the Danish Hospital Discharge
      Registry. We determined the first hospitalization with a discharge diagnosis of
      asthma as recorded in the Danish Hospital Discharge Registry. RESULTS: Most
      pregnant women (81.5%) drank at least some alcohol during pregnancy, but only a
      few (2.1%) consumed 120 g or more per week. In total, 307 children were
      hospitalized at least once with a discharge diagnosis of asthma during follow-up
      (the cumulative incidence risk was 3.5% from birth to 12 years of age or the end
      of follow-up). After adjusting for maternal socioeconomic factors, dietary
      components, and other lifestyle factors, children whose mothers drank alcohol
      during pregnancy did not have an increased risk of hospitalization with asthma
      compared with the children of mothers who reported no alcohol consumption during
      pregnancy (adjusted incidence rate ratio, 0.95; 95% confidence interval, 0.70
      1.29). Further analyses showed no association with the dose and type of alcohol
      or with binge drinking. CONCLUSIONS: The study provides no support for a causal
      link between maternal alcohol intake during pregnancy and asthma in childhood.

PMID- 15166653
TI  - Serum ceruloplasmin and ferroxidase activity are not decreased in hepatic failure
      related to alcoholic cirrhosis: clinical and pathophysiological implications.
AB  - BACKGROUND: A decrease in serum ceruloplasmin (Cp), a protein involved in iron
      metabolism through its ferroxidase activity, is classically claimed to be
      observed in severe hepatic failure of non-wilsonian chronic liver disease and
      therefore to be a confounding factor for the diagnosis of Wilson's disease.
      Moreover, a simultaneous decrease in ferroxidase activity could be hypothesized
      as playing a role in the development of the hepatic siderosis frequently observed
      in advanced chronic liver diseases. The aim of this study was to test the
      validity of these two statements. METHODS: This study investigated Cp, determined
      by immunonephelometry, and its ferroxidase 1 activity determined by Erel's method
      in 33 male patients with severe alcoholic cirrhosis compared with 66 healthy male
      volunteers, selected on strict criteria. Each patient was age-matched with two
      controls. Nonparametric tests were used for statistical analysis. RESULTS: The
      mean values of Cp were significantly higher in cirrhotic patients as compared
      with control subjects. A significant elevation of Cp was also observed in the
      subgroup of 11 cirrhotic patients who had normal serum C-reactive protein levels.
      The mean values of ferroxidase 1 activity were similar to those obtained in
      control subjects. CONCLUSIONS: Low serum Cp should not be expected in severe
      hepatic cirrhosis of non-wilsonian origin. Hepatic siderosis in advanced chronic
      liver disease is likely to be unrelated to decreased ferroxidase activity.

PMID- 15166652
TI  - Illegal alcohol sales to obviously intoxicated patrons at licensed
      establishments.
AB  - BACKGROUND: Early studies assessing propensity of alcohol sales to underage youth
      found that, before intervention, likelihood of licensed alcohol establishments
      selling alcohol to underage youth was 50% or higher across many communities.
      Community-wide interventions successfully lowered underage alcohol sales rates in
      several communities. Across studies assessing propensity for alcohol sales to
      obviously intoxicated patrons, sales rate estimates ranged from 58% to 85% for on
      premise establishments (e.g., bars). No previous studies have assessed likelihood
      of alcohol sales to obviously intoxicated patrons in off-premise establishments
      (e.g., liquor stores). One goal of this study was to assess propensity for
      illegal alcohol sales to obviously intoxicated patrons at on- and off-premise
      establishments. Another goal was to assess whether server and/or establishment
      characteristics were related to the likelihood of illegal sales. Results may
      inform future interventions to reduce illegal alcohol sales at licensed alcohol
      establishments. METHODS: Trained actors attempted to purchase alcohol while
      acting out signs of obvious intoxication at a census of on- and off-premise
      alcohol establishments (n = 372) in 11 communities. The outcome variable was
      whether an establishment sold alcohol to a buyer. Independent variables included
      age and gender of server/clerk, type of establishment, area, exterior
      maintenance, type of license, and time of purchase attempt. Bivariate and
      multivariate analyses were conducted. RESULTS: Seventy-nine percent of the
      establishments sold alcohol to a buyer (83% and 76% at off- and on-premise
      establishments, respectively). Servers/clerks who appeared younger than age 31
      and off-premise establishments were significantly more likely than older
      appearing servers and on-premise establishments to sell alcohol to buyers.
      CONCLUSIONS: The likelihood of alcohol sales to obviously intoxicated patrons in
      licensed alcohol establishments is very high. Interventions to reduce illegal
      alcohol sales to intoxicated patrons are needed.

PMID- 15166654
TI  - Effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate,
      testosterone, and estradiol levels in middle-aged men and postmenopausal women: a
      diet-controlled intervention study.
AB  - BACKGROUND: Moderate alcohol consumption is inversely associated with
      cardiovascular diseases. Changes in hormone levels might in part help explain the
      positive health effect. This study was performed to examine the effect of
      moderate alcohol consumption on plasma dehydroepiandrosterone sulfate (DHEAS),
      testosterone, and estradiol levels. METHODS: In a randomized, diet-controlled,
      crossover study, 10 middle-aged men and 9 postmenopausal women, all apparently
      healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol
      beer with dinner during two successive periods of 3 weeks. During the beer
      period, alcohol intake equaled 40 and 30 g per day for men and women,
      respectively. The total diet was supplied and had essentially the same
      composition during these 6 weeks. Before each treatment there was a 1 week
      washout period, in which the subjects were not allowed to drink alcoholic
      beverages. At the end of each of the two experimental periods, fasting blood
      samples were collected in the morning. RESULTS: Moderate alcohol consumption
      increased plasma DHEAS level by 16.5% (95% confidence interval, 8.0-24.9), with
      similar changes for men and women. Plasma testosterone level decreased in men by
      6.8% (95% confidence interval, -1.0- -12.5), but no effect was found in women.
      Plasma estradiol level was not affected. Serum high-density lipoprotein
      cholesterol level increased by 11.7% (95% confidence interval, 7.3-16.0), with
      similar changes for men and women. The overall alcohol-induced relative changes
      in DHEAS, testosterone, and estradiol correlated positively with the relative
      increase in high-density lipoprotein cholesterol (adjusted for the relative
      change in body weight); however, findings were only borderline significant for
      DHEAS and estradiol (r = 0.44, p = 0.08; r = 0.32, p = 0.21; and r = 0.46, p =
      0.06, respectively). CONCLUSIONS: A protective effect of moderate alcohol
      consumption for cardiovascular disease risk may in part be explained by increased
      plasma DHEAS level.

PMID- 15166655
TI  - Effect of dealcoholized beer (Bitburger Drive) consumption on hemostasis in
      humans.
AB  - BACKGROUND: The beneficial effect of moderate alcohol consumption in lowering the
      risk of cardiovascular disease has been shown in several epidemiologic studies.
      Such studies have also shown, however, that the protective effect of alcoholic
      beverages like wine and beer is not only due to the ethanol content but also to
      the presence of nonalcoholic constituents. The positive effect of alcoholic
      beverages has been attributed to changes in lipoprotein metabolism, but there is
      substantial evidence that effects on hemostasis play an important role. Whether
      the effects of alcoholic beverages on hemostasis are due exclusively to ethanol
      or are due, in part, to nonalcoholic components, is still under debate. METHODS:
      We have examined the hemostatic effects of 3 liters of beer, dealcoholized beer,
      and ethanol/water (v/v 4%), consumed over a period of 3 hr, in 12 young healthy
      volunteers. Platelet parameters CD62, PAC-1, and monocyte platelet aggregates
      were analyzed using flow cytometric measurements. The activity of factor VII was
      determined with a prothrombin time (PT) assay and plasminogen activator inhibitor
      activity using a chromogenic substrate. Thrombin generation was determined
      according to the method of Hemker. RESULTS: All three fluids administered,
      dealcoholized beer, beer, and ethanol, reduced the expression of activated
      fibrinogen receptor, the platelet activation marker CD62, and the formation of
      monocyte-platelet-aggregate. In addition, dealcoholized beer also showed
      significant inhibitory effects on thrombin generation, whereas beer and ethanol
      showed procoagulatory effects. CONCLUSIONS: This study has shown that the acute
      consumption of dealcoholized beer inhibits thrombogenic activity in young adults.
      This action could have a beneficial effect on the development of coronary artery
      disease. Thus, the consumption of dealcoholized beer could provide cardiovascular
      benefit without the negative effects of alcohol.

PMID- 15166656
TI  - Influence of ethanol dependence and methionine enkephalin antisense on serum
      endomorphin-1 and methionine enkephalin levels.
AB  - BACKGROUND: Opiate peptides are involved in the physical dependence on ethanol.
      Levels of methionine enkephalin (MEnk), for example, are affected by ethanol. No
      study on the effect of ethanol on endomorphin, the endogenous ligand for the mu
      opiate receptor, has yet been conducted. METHODS: We examined the effect of
      ethanol ingestion on serum endomorphin (EM)-1 and MEnk levels. We also determined
      the effect of antisense directed at MEnk on serum levels of EM-1 and MEnk.
      RESULTS: Serum EM-1 levels steadily decreased about 20% during 56 days of ethanol
      ingestion in liquid feed, whereas a similar decrease in serum MEnk levels was not
      statistically significant. Serum MEnk levels decreased about 20% by 48 hr after
      antisense injection and then returned to baseline, whereas serum EM-1 levels
      increased by about 80% and remained elevated for about 2 weeks. In mice not
      treated with antisense or alcohol, there was no correlation between the serum
      levels of EM-1 and MEnk. CONCLUSIONS: These results show that serum levels of EM
      1 are decreased by physical dependence on ethanol and that this effect is not
      directly mediated through MEnk.

PMID- 15166657
TI  - Epidermal growth factor prevents acetaldehyde-induced paracellular permeability
      in Caco-2 cell monolayer.
AB  - BACKGROUND: Intestinal permeability and endotoxemia play a crucial role in the
      pathogenesis of alcoholic liver disease. Previous studies showed that
      acetaldehyde disrupts intestinal epithelial barrier function and increases
      paracellular permeability by a tyrosine kinase-dependent mechanism. In the
      present study, the role of epidermal growth factor (EGF) in protection of
      epithelial barrier function from acetaldehyde was evaluated in Caco-2 intestinal
      epithelial cell monolayer. METHODS: Caco-2 cells on Transwell inserts were
      exposed to acetaldehyde in the absence or presence of EGF, and the paracellular
      permeability was evaluated by measuring transepithelial electrical resistance and
      unidirectional flux of inulin. Integrity of epithelial tight junctions and
      adherens junctions was analyzed by confocal immunofluorescence microscopy and
      immunoblot analysis of occludin, zonula occludens (ZO)-1, E-cadherin, and beta
      catenin in the actin cytoskeleton. Reorganization of actin cytoskeletal
      architecture was examined by confocal microscopy. RESULTS: Acetaldehyde increased
      paracellular permeability to inulin and lipopolysaccharide, and EGF significantly
      reduced these effects of acetaldehyde in a time- and dose-dependent manner. EGF
      prevented acetaldehyde-induced reorganization of occludin, ZO-1, E-cadherin, and
      beta-catenin from the cellular junctions to the intracellular compartments.
      Acetaldehyde treatment induced a reorganization of actin cytoskeletal network and
      reduced the levels of occludin, ZO-1, E-cadherin, and beta-catenin associated
      with the actin cytoskeleton. EGF effectively prevented acetaldehyde-induced
      reorganization of actin cytoskeleton and the interaction of occludin, ZO-1, E
      cadherin, and beta-catenin with the actin cytoskeleton. CONCLUSION: These results
      indicate that EGF attenuates acetaldehyde-induced disruption of tight junctions
      and adherens junctions and prevents acetaldehyde-induced reorganization of actin
      cytoskeleton and its interaction with occludin, ZO-1, E-cadherin, and beta
      catenin.

PMID- 15166658
TI  - Fetal learning with ethanol: correlations between maternal hypothermia during
      pregnancy and neonatal responsiveness to chemosensory cues of the drug.
AB  - BACKGROUND: Fetuses learn about ethanol odor when the drug is present in the
      amniotic fluid. Prenatal learning comprising ethanol's chemosensory cues also
      suggests an acquired association between ethanol's chemosensory and
      postabsorptive properties. Ethanol-related thermal disruptions have been
      implicated as a significant component of the drug's unconditioned properties. In
      the present study, ethanol-induced thermal changes were analyzed in pregnant rats
      subjected to a moderate ethanol dose. This thermal response was later tested for
      its correlation with the responsiveness of the progeny to ethanol and nonethanol
      chemosensory stimuli. METHODS: During gestational day (GD) 14, pregnant rats were
      subjected to a minor surgical procedure to place a subcutaneous telemetric
      thermal sensor in the nape of the neck. During GDs 17 to 20, females received a
      daily intragastric administration of ethanol (2 g/kg) or water, using solutions
      kept at room temperature. Maternal body temperatures were recorded before and
      after (4 consecutive hours) the administration of water or ethanol. Newborns
      representative of both prenatal treatments were tested in terms of behavioral
      activity elicited by the smell of ethanol or of a novel odorant (cineole). A
      third group of pups were tested in response to unscented air stimulation.
      RESULTS: Ethanol administration during late gestation induced reliable maternal
      hypothermia, a thermal disruption greater than that observed in water-treated
      females. It was systematically observed that maternal ethanol-induced hypothermia
      negatively correlated with neonatal motor reactivity elicited by ethanol
      olfactory stimulation. No other significant correlations were observed in terms
      of responsiveness to cineole or to unscented air in animals prenatally exposed to
      ethanol or water. CONCLUSIONS: In conjunction with prior research, the present
      results indicate that fetal ethanol exposure may yield learning of an association
      between ethanol's sensory and unconditioned properties. Ethanol-induced
      hypothermia during late gestation seems to represent a significant component of
      ethanol's unconditioned consequences. Specifically, ethanol-related thermal
      disruptions in the womb are highly predictive of neonatal responsiveness to
      ethanol's chemosensory cues that are known to be processed by the near-term
      fetus.

PMID- 15166659
TI  - Alcohol-induced lipid and morphological changes in chick retinal development.
AB  - BACKGROUND: Alcohol exposure causes alterations in the lipid content of different
      organs and a reduction of long-chain fatty acids. During embryo development, the
      central nervous system is extremely vulnerable to the teratogenic effects of
      alcohol, and the visual system is particularly sensitive. METHODS: White Leghorn
      chick embryos were injected with 10- and 20-microl alcohol doses into the yolk
      sac at day 6 of incubation. The lipid composition of the retina was analyzed in
      embryos at day 7 of incubation (E7), E11, E15, and E18. The percentages of
      phospholipids, free cholesterol, esterified cholesterol, diacylglycerides, and
      free fatty acids were estimated by using an Iatroscan thin layer chromatography
      flame ionization detector. Gas chromatography and mass spectrometry were used to
      determine fatty acid composition. The morphological study was performed at E7,
      E11, and E19 by means of semithin and immunohistochemical techniques. RESULTS: In
      the retina, alcohol causes the total lipid content to change, with a remarkable
      increase in free cholesterol and a dramatic decrease in esterified cholesterol.
      Diacylglycerides and free fatty acids tend to increase. Phosphatidylcholine and
      phosphatidylethanolamine decrease, whereas phosphatidylserine, sphingomyelin, and
      phosphatidylinositol increase. The main fatty acids of the retina also undergo
      changes. At E7, myriotic acid increases, and oleic acid and polyunsaturated fatty
      acids such as arachidonic acid and docosahexaenoic acid decrease. From E18
      onward, there is some recovery, except for fatty acids, which recover earlier.
      From a morphological point of view, alcohol effects on retinal development are
      various: increase of intercellular spaces in all cell layers, pyknosis with loss
      of cellularity in the inner nuclear cell layer and ganglion cell layer, retarded
      or disorderly cell migration, early cell differentiation, and loss of
      immunoreactivity for myelin oligodendrocyte-specific protein. CONCLUSIONS: Acute
      alcohol exposure during embryo development causes the lipid composition of the
      retina to change, with a trend to recovery in the last stages. These alterations
      are in line with the changes observed at a morphological level.

PMID- 15166660
TI  - Acute alcohol consumption inhibits accessory cell function of monocytes and
      dendritic cells.
AB  - BACKGROUND: Alcohol affects both innate and acquired immune responses. Chronic
      alcoholics have reduced delayed-type hypersensitivity response and increased
      susceptibility to infections. In contrast, recent studies suggest that acute,
      moderate alcohol consumption has protective effects on mortality. Monocytes and
      dendritic cells (DC) play a central role in coordination of innate and adaptive
      immune responses and are pivotal in activation of T lymphocytes in an antigen
      specific manner. In this study, we investigated the effects of acute, moderate
      alcohol consumption on antigen presenting cell function of blood monocytes and
      monocyte-derived myeloid dendritic cells. METHODS: Accessory cell function of
      human blood monocytes was tested before and after acute alcohol intake (2 ml
      vodka/kg body weight) by measuring T cell activation with alloantigen (mixed
      lymphocyte reaction, MLR), superantigen (staphylococcal enterotoxin B) and recall
      antigen (tetanus toxoid). Myeloid DCs were generated in vitro from monocytes
      obtained from these individuals using IL-4 and GM-CSF and their allostimulatory
      function was tested in an MLR. RESULTS: We found significantly reduced T cell
      proliferation in the presence of monocytes obtained 2 or 18 hr after alcohol
      consumption whether alloantigen, superantigen, or recall antigen was the stimuli
      (p < 0.01). The reduced T cell proliferation was due to the effects of acute
      alcohol on monocytes rather than on T cells as we found decreased proliferation
      only in the presence of alcohol-exposed accessory cells but not when T cells were
      exposed to alcohol. In addition, monocyte-derived dendritic cells showed
      significantly reduced allostimulatory capacity after alcohol consumption (p <
      0.005). CONCLUSION: Acute alcohol consumption inhibits accessory cell function of
      both monocytes and myeloid dendritic cells. Impaired function of these key
      antigen-presenting cells may contribute to reduced adaptive immune responses and
      increased susceptibility to infections when acute alcohol intake coincides with
      exposure to pathogens.

PMID- 15166661
TI  - Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a
      significant immunohistochemical pitfall compounding the differential diagnosis
      with prostatic adenocarcinoma.
AB  - Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a
      useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid
      in its distinction from its many mimics, one of which is the benign lesion,
      nephrogenic adenoma (NA). The goal of this study was to assess the expression of
      AMACR in NA by immunohistochemistry, as well as other potentially useful markers,
      high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific
      antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and
      underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases
      showed circumferential granular cytoplasmic AMACR expression of at least moderate
      intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining
      case. The AMACR-positive cases in the bladder typically showed focal weak
      noncircumferential staining of the tubules and stronger staining of the cells
      lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and
      4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63
      and PSA were negative in all cases. Our data indicate that NA of the prostatic
      urethra commonly expresses AMACR and lacks basal cell-specific markers, making it
      not only a potential morphologic mimic of prostatic adenocarcinoma but also a
      significant immunohistochemical mimic as well. Awareness of NA as a significant
      pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of
      hematoxylin and eosin-stained sections remains the key to the correct diagnosis,
      which can be supported by a negative PSA stain.

PMID- 15166662
TI  - More differences between HNPCC-related and sporadic carcinomas from the
      endometrium as compared to the colon.
AB  - PURPOSE: Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related
      endometrial carcinoma from sporadic carcinoma by histologic features as compared
      with colonic cases. STUDY DESIGN: Case-control study. METHODS AND MATERIALS: From
      the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6)
      endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC
      related tumor, 2 sporadic control cases were included. The tumors were evaluated
      for the following 7 pathologic features: tumor differentiation, T-stage, growth
      pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation,
      presence of lymphangioinvasive growth, and the amount of tumor-infiltrating
      lymphocytes. RESULTS: HNPCC-related endometrial carcinomas were significantly
      more often poorly differentiated (83% versus 27%), more often showed the presence
      of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth
      (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more
      often present (100% versus 36%) compared with sporadic endometrial carcinomas.
      The differences between HNPCC and sporadic colorectal cancer specimens were less
      discriminating. CONCLUSIONS: HNPCC-related endometrial carcinomas are
      characterized by poor differentiation, more frequent Crohn-like lymphoid
      reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes.
      These features therefore might form the basis for selecting patients for
      counseling in a hereditary cancer clinic or testing for microsatellite
      instability or mutation analysis of mismatch repair genes, especially when they
      are of relatively young age.

PMID- 15166663
TI  - Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of
      microsatellite instability.
AB  - High levels of microsatellite instability (MSI-H) result from abnormal nucleotide
      mismatch repair in a subset of sporadic colorectal carcinomas (CRC) and in most
      CRC of hereditary non-polyposis colorectal cancer syndrome. CRC with MSI-H have
      distinctive clinical-pathologic features, but the immunophenotype has not been
      studied extensively. We evaluated immunohistochemical expression of cytokeratin 7
      (CK7), cytokeratin 20 (CK20), and pancytokeratin (panCK) in 44 CRC from 22 paired
      MSI-H and microsatellite-stable (MSS) cases matched for clinical-pathologic
      characteristics. The mean percentage of CK20+ tumor cells was 84 +/- 6% in MSS
      CRC but only 37 +/- 8% in MSI-H CRC (P = 0.0007). Thirty-two percent (7/22, 95%
      confidence interval 14-55%) of MSI-H CRC were CK20-, as contrasted with 9% (2/22,
      95% CI 1-29%, P = 0.13) of MSS CRC. CK20 expression was inversely correlated with
      levels of MSI (rs = -0.45, P = 0.006). CK7+ was infrequent (16%, 7/44, 95% CI 7
      30%) and panCK+ was universal, with no significant differences between MSI-H and
      MSS CRC. Our study shows that decreased or even absent CK20 expression is a
      phenotypic characteristic of MSI-H CRC and that MSI-H explains much of the subset
      of CRC that lack CK20 expression. Our results also indicate that regulation of
      CK20 gene expression involves molecular pathways that are altered by MSI-H.

PMID- 15166665
TI  - Diffuse large B-cell lymphomas with plasmablastic differentiation represent a
      heterogeneous group of disease entities.
AB  - Plasmablastic lymphoma was initially described as a variant of diffuse large B
      cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and
      characterized by immunoblastic morphology and a plasma cell phenotype. However,
      other lymphomas may exhibit similar morphologic and immunophenotypic features. To
      determine the significance of plasmablastic differentiation in DLBCL and examine
      the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs
      with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell
      differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several
      distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma
      of the oral mucosa type and showed a monomorphic population of immunoblasts with
      no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was
      positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the
      remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases
      were classified as plasmablastic lymphoma with plasmacytic differentiation. These
      were composed predominantly of immunoblasts and plasmablasts, but in addition
      exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV
      was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically
      indistinguishable from the previous group, were secondary extramedullary
      plasmablastic tumors occurring in patients with prior or synchronous plasma cell
      neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms
      were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+
      DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In
      conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group
      of neoplasms with different clinicopathological characteristics that may
      correspond to different entities.

PMID- 15166664
TI  - Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic
      lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50
      patients.
AB  - A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic
      T-cell lymphomas of the skin has been recently described, and some have been
      included as distinct clinicopathologic entities in the classification of
      hematologic malignancies recently proposed by the World Health Organization. In
      the European Organization for Research and Treatment of Cancer classification for
      cutaneous lymphomas, they would be classified either as CD30- large T-cell
      lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell
      lymphoma. Precise clinicopathologic and prognostic features of all of them have
      not yet been well characterized. We studied retrospectively 81 biopsies from 50
      patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non
      mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic,
      phenotypical, and genetic features and data on Epstein-Barr virus association
      allowed us to classify our cases according to the following 7 categories: a)
      subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5
      year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year
      survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated
      5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated
      5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases
      (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell
      lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large
      pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows
      that these cutaneous lymphomas can be classified according to precise diagnostic
      categories. With the exception of SPTCL, analysis of follow-up data from our
      patients showed that these groups of lymphomas are characterized by an aggressive
      course, regardless of the diagnostic category.

PMID- 15166666
TI  - Neoplastic cells do not carry bcl2-JH rearrangements detected in a subset of
      primary cutaneous follicle center B-cell lymphomas.
AB  - Whether primary cutaneous follicular lymphoma (PCFL) may or not represent a
      cutaneous equivalent to nodal follicular lymphoma (FL) is not determined. We have
      therefore investigated a series of PCFL to determine if tumoral cells carry or
      not the t(14;18)(q32;q21) translocation, a cytogenetic hallmark of nodal FL.
      Thirty cases of PFCL were selected according to the criteria of both the European
      Organisation for Research and Treatment of Cancer and the World Health
      Organization with 21 cases classified as grade 1 or 2 and 9 cases as grade 3.
      First, cutaneous tumors were studied by PCR for the amplification of bcl-2/JH
      rearrangements and by interphase fluorescence in situ hybridization using a dual
      color probe spanning t(14;18) breakpoints. Second, we tried to determine the
      origin of bcl2-JH-positive cells by a parallel bcl2-JH and immunoglobulin heavy
      chain gene amplification of blood mononuclear cells DNA and of DNA extracted from
      single microdissected B cells. Bcl2-JH rearrangements were amplified by PCR in
      skin of 9 of 30 (30%) patients with a similar-sized bcl2-JH rearrangement
      detected in the blood of 7 of these 9 cases. No t(14;18) breakpoint was detected
      by interphase fluorescence in situ hybridization analysis of 11 bcl2-JH-negative
      and 5 bcl2-JH-positive PCFL in contrast with its detection in the secondary
      cutaneous FL and in the nodal FL cases. Single-cell/multigene analysis showed
      that no single monoclonal B cells of PCFL carried the bcl2-JH rearrangement.
      Bystander or nontumoral t(14;18)+ B cells emigrating from blood may account for
      the detection of bcl2-JH rearrangements within PCFL material. Our study also
      underlines the diagnostic value of interphase fluorescence in situ hybridization
      to discriminate between t(14;18)-negative PCFL and extracutaneous FL involving
      the skin.

PMID- 15166667
TI  - Benign notochordal cell tumors: A comparative histological study of benign
      notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal
      intervertebral discs.
AB  - Intraosseous benign notochordal cell tumors are recently recognized conditions
      that may undergo malignant transformation to classic chordomas. This study
      attempts to define the morphologic and immunohistochemical characteristics of 34
      benign notochordal cell tumors by contrasting them with classic chordomas and the
      notochordal vestiges in fetal intervertebral discs. Benign notochordal cell
      tumors were characterized by well-demarcated though unencapsulated sheets of
      adipocyte-like vacuolated and less vacuolated eosinophilic cells within axial
      bones. The round nuclei were mildly polymorphic but bland. The tumor cells often
      contained cytoplasmic eosinophilic hyaline globules and lack any intercellular
      myxoid matrix or necrosis. The involved bone trabeculae were often sclerotic
      without evidence of bone destruction. The histologic features were different from
      those of both notochordal vestiges in fetal intervertebral discs and classic
      chordomas. There was overlap in immunohistochemical reactivity of benign
      notochordal cell tumors and chordomas, but notochordal vestiges failed to
      demonstrate cytokeratin 18 positivity. A more appropriate term for the lesions is
      "benign notochordal cell tumor" rather than "notochordal rest" or "notochordal
      hamartoma" as they are not rests and do not fulfill the definition of hamartoma.
      Benign notochordal cell tumors do not need any surgical procedure and must be
      adequately recognized to prevent unnecessary operations.

PMID- 15166668
TI  - Small cell carcinoma of the major salivary glands: clinicopathologic study with
      emphasis on cytokeratin 20 immunoreactivity and clinical outcome.
AB  - Small cell carcinomas arising in salivary glands, extremely rare high-grade
      malignant tumors, are subclassified into neuroendocrine and ductal types. The
      neuroendocrine type may be segregated further into Merkel cell and pulmonary
      varieties according to cytokeratin 20 immunoreactivity. Whether subclassification
      of this tumor group has any biologic or clinical significance is not known. We
      examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma
      of major salivary glands from a single institution and analyzed their
      clinicopathologic profiles, including immunohistochemical features and prognostic
      factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive
      immunostaining, often with a paranuclear dotlike pattern of reactivity. All
      tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined,
      and 6 tumors were also positive for neurofilament, with a paranuclear dotlike
      pattern. Postoperatively, 9 patients developed metastatic disease, and 10
      patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By
      log-rank analysis, overall survival was reduced significantly for patients with a
      primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain
      reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for
      neuroendocrine markers (P = 0.034). These results indicate that small cell
      carcinoma of major salivary glands is a highly aggressive tumor, although the
      prognosis may be better than for extrasalivary neoplasms. Our data also suggest
      that most salivary gland small cell carcinomas exhibit neuroendocrine
      differentiation. Immunohistochemical expression of cytokeratin 20 can be used to
      classify salivary small cell carcinomas into Merkel cell and pulmonary types and
      may have prognostic significance.

PMID- 15166669
TI  - Malignant melanoma involving the ovary: a clinicopathologic and
      immunohistochemical study of 23 cases.
AB  - Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare
      tumor and in the absence of a previous diagnosis can represent a diagnostic
      challenge. We present the clinicopathologic and immunohistochemical features of
      23 cases seen in our institution over a period of 40 years (1962-2001). The
      patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known
      in 19 patients: 14 white, 4 Hispanic, and 1 black. A previous history of MM was
      definitively obtained in 14 patients; in these cases, the interval between the
      primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7
      months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size
      ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic
      teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases
      (35%). The architectural pattern was nodular (8 cases), diffuse (6 cases),
      nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a
      teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular
      areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor
      cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and
      spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18
      cases, and nuclear inclusions were present but rare in the majority of cases.
      Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in
      10 cases, and was absent in 5 cases. In 8 cases, initial diagnoses included sex
      cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S
      100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15
      cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was
      positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases.
      Treatment performed in 18 of the cases are as follows: oophorectomy with/without
      chemotherapy (10); total abdominal hysterectomy with bilateral salpingo
      oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral
      salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy
      with salpingo-oophorectomy (1). Follow-up ranging from 2 to 96 months was
      available in 18 patients. All but one had metastases in other organs, most often
      in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive
      with disease (6-18 months), and 2 have no evidence of disease at 24 and 96
      months; one was the patient with melanoma arising within a teratoma. In
      conclusion, MM involving the ovary is a rare disease, predominantly seen in women
      of reproductive age, and is associated with a poor prognosis. The tumor is most
      often metastatic from another site and is unilateral in most cases. Nodular or
      diffuse pattern and epithelioid cell type are most frequently seen, and the tumor
      can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most
      sensitive marker. MART-1 was positive in the few cases that were negative with
      HMB-45. Inhibin can be focally positive in some cases.

PMID- 15166670
TI  - Cutaneous angiosarcoma following breast-conserving surgery and radiation: an
      analysis of 27 cases.
AB  - Iatrogenic angiosarcomas (AS), following treatment of breast carcinomas and
      attributed to chronic lymphedema, were first described by Stewart and Treves.
      With emphasis on breast-conserving therapy combined with adjuvant radiation, a
      recently recognized form of cutaneous postradiation angiosarcoma of the breast
      (CPRASB) has emerged. To more completely characterize CPRASB, 27 cases were
      analyzed. Histologic features studied included pattern of growth (vasoformative,
      sieve-like, or solid), nuclear grade, necrosis, and mitotic rate. Clinical and
      follow-up information was obtained. The patients received relatively standard
      radiation treatment. The median interval to diagnosis of CPRASB was 59 months; 5
      occurred in less than 3 years. Lymphedema was largely absent, and when present
      was only mild in nature. CPRASB was frequently multifocal at presentation (13 of
      27). All tumors had a vasoformative pattern of growth; the majority (16 of 27)
      had areas with a sieve-like pattern. The solid pattern was less frequent (7 of
      27). The majority had high-grade nuclear features (16 grade 3, 8 grade 2, 3
      grade1). The mean mitotic rate was 9/10 HPF. Necrosis was rare (2 of 27). All
      were treated with wide excision or mastectomy. Follow-up was available on 22 of
      27 cases (median 44 months). Fourteen experienced local recurrence and 6 had
      multiple recurrences. Metastasis was documented in 9 of 22 patients and involved
      lungs (6), contralateral breast (3), skeleton (2), lymph nodes (1), and soft
      tissue (1). Eight patients died of disease, 2 died with disease, 4 were alive
      with disease, and 8 are alive without disease. The median interval to death was
      33.5 months. All 4 patients with disease have documented metastasis. CPRASB
      differs from Stewart-Treves AS by its shorter latency period and lack of
      association with lymphedema.

PMID- 15166671
TI  - Carcinoma arising from preexisting pregnancy-like and cystic hypersecretory
      hyperplasia lesions of the breast: a clinicopathologic study of 9 patients.
AB  - The intimate histologic relationship of pregnancy-like hyperplasia (PLH) and
      cystic hypersecretory hyperplasia (CHH) has been previously reported. However,
      none of these published cases contained coexisting carcinoma. In this study, we
      describe 9 additional cases of this lesion, all of which also revealed ductal
      carcinoma in situ (DCIS) as well as invasive carcinoma in 1 case. Hematoxylin and
      eosin-stained slides were reviewed for all cases. All were women who ranged in
      age from 35 to 49 years (mean 42.0 years; median 42.5 years). Reasons for
      surgical biopsy were calcifications in 6, breast mass in 2, and nipple discharge
      in 1. One patient with a mass also experienced nipple discharge. Three women
      initially underwent needle core biopsy and 6 had an excisional biopsy. Six women
      ultimately had mastectomies. Histologically, 5 had CHH merging with coexisting
      PLH. Atypia was seen in one or both components. All 9 cases contained DCIS. Two
      cases showed micropapillary DCIS, one of which appeared to arise from atypical
      PLH, while 4 of the 7 cases containing cystic hypersecretory DCIS appeared to
      arise from coexisting atypical CHH. Well-differentiated invasive carcinoma was
      identified in 1 case adjacent to cystic hypersecretory DCIS. Subsequent sentinel
      lymph node biopsy in this case revealed micrometastatic disease. Clinical follow
      up was obtained in 9 patients and ranged from 10 to 69 months. All patients were
      free of disease at the time of last follow-up. Careful clinical follow-up is
      recommended for lesions that display atypia in PLH, CHH, or a histologically
      combined lesion. If these lesions are found on a needle core biopsy specimen, an
      excisional biopsy is recommended. DCIS, usually micropapillary or cystic
      hypersecretory types, and rarely invasive carcinoma can arise in this setting.
      Affected patients are typically younger than those with more common types of
      breast carcinoma.

PMID- 15166672
TI  - Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic
      stem cell transplantation.
AB  - Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized
      complication of conventional bone marrow/stem cell and solid organ
      transplantation. However, not much is known about PTLD following the more
      recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST).
      This study reports the findings from two cases of PTLD following NMST and
      compares them to the one previously reported case. The donor origin of the PTLD
      was determined using short tandem repeat analysis, and B- and T-cell clonalities
      were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total
      of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both
      patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab,
      anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs
      were EBV positive (by immunohistochemistry and in situ hybridization) with
      diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of
      PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from
      the previously reported case). All three PTLDs arose 6 to 7 months after NMST and
      were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV
      positive, diffuse large B-cell lymphoma.

PMID- 15166673
TI  - Consistent immunostaining for cyclin D1 can be achieved on a routine basis using
      a newly available rabbit monoclonal antibody.
AB  - Rabbit monoclonal antibody (MAb), which has become available only recently,
      theoretically combines the advantage of the high affinity attributable to its
      rabbit origin and the high specificity due to its monoclonal nature. Since
      immunohistochemical demonstration of cyclin D1 is notoriously difficult, this
      study aims to assess whether a newly available rabbit MAb against cyclin D1 (SP4)
      can improve the consistency of immunostaining, especially for the diagnosis of
      mantle cell lymphoma (MCL). A total of 150 cases of lymphoproliferative lesions,
      including 30 cases of MCL, histologic mimickers of MCL, and various types of
      lymphomas and leukemias, were studied. Immunostaining was performed on formalin
      fixed, paraffin-embedded tissue sections using a labeled streptavidin-biotin
      peroxidase system in an automated immunostainer. All cases of MCL expressed
      cyclin D1, with a higher median staining score (8 out of a maximum of 12)
      compared with mouse MAb DCS-6 (score 4). In addition, 2 of 15 cases of B-cell
      chronic lymphocytic leukemia (B-CLL), 3 of 12 cases of multiple myeloma, and 2 of
      5 cases of hairy cell leukemia were also positive. Comparable staining results
      could also be achieved by an optimized manual staining protocol. This study thus
      confirms the superior performance of the rabbit MAb SP4, which should permit
      consistent immunostaining for cyclin D1 to be readily achieved. The value of
      cyclin D1 immunohistochemistry in the differential diagnosis of MCL from other
      low-grade B-cell lymphomas is also affirmed, but with the caveat that rare cases
      of B-CLL can also be cyclin D1 positive.

PMID- 15166674
TI  - Desmoplastic small cell tumor in the pancreas.
AB  - Desmoplastic small cell tumor (DSCT) is a distinct type of small blue cell tumors
      and is characterized by the unique karyotypic aberration involving the fusion of
      the Ewing's sarcoma (EWS) gene and Wilms' tumor (WT1) gene. Typically, it grows
      along serosal surfaces; however, in some cases, the tumor presents as a dominant
      mass in an internal organ. Examples of DSCT forming a primary mass in ovary,
      testes, and brain have been described, but its presentation as a primary
      pancreatic mass has not been reported previously. The case reported here is a 31
      year-old woman who presented with a 14-cm mass in the pancreas. There were
      smaller nodules on the peritoneal surfaces that were regarded clinically as
      metastasis from a primary pancreatic tumor. During the frozen section, the
      diagnosis of a poorly differentiated endocrine carcinoma of pancreatic origin was
      rendered and patient underwent subtotal pancreatectomy. On microscopic
      examination, the tumor was composed of large nests and broad bands of small blue
      cells, separated by fibrous stroma. Immunohistochemical stains showed positivity
      of the tumor cells for cytokeratins (AE1:AE3 and CAM5.2), neuron specific
      enolase, desmin and WT1, whereas chromogranin, S-100, and CD99 were negative.
      Since this immunoprofile is characteristic of DSCT, molecular analysis was
      performed which revealed the presence of EWS-WT1 gene fusion characteristic of
      DSCT. This case shows that in addition to primary pancreatic tumors characterized
      by prominent cellularity such as solid pseudopapillary tumors, acinar cell
      carcinoma, pancreatoblastoma, endocrine tumors, and other small blue cell tumors,
      the differential diagnosis of cellular, stroma-poor neoplasia in the pancreas
      also includes DSCT. This case is also another demonstrative example of how DSCT
      may form a dominant mass in intraabdominal organs.

PMID- 15166675
TI  - Ductuloinsular tumors of the pancreas: endocrine tumors with entrapped
      nonneoplastic ductules.
AB  - Rare pancreatic neoplasms have been reported that show both endocrine and
      exocrine differentiation in the neoplastic components. In addition, pancreatic
      endocrine tumors may contain small, cytologically bland ductules intimately
      admixed with the endocrine component. It was recently suggested that these
      ductules represent an intrinsic part of the tumor, ie, that the ductules are
      neoplastic, and the term "ductulo-insular tumors of the pancreas" was proposed.
      In the present study, the nature of the ductular component of 16 cases of ductule
      containing pancreatic endocrine tumors was investigated at the molecular level.
      Molecular genetic changes often present in ductal pancreatic neoplasms were not
      found by immunohistochemistry for DPC4, p53, and ERBB2 and by sequence analysis
      of KRAS codon 12. An X-chromosome inactivation clonality assay of one such tumor
      from a female patient indicated that the neuroendocrine component was monoclonal,
      contrasting with the ductular component that was polyclonal. The lymph node and
      liver metastases from three patients only contained the neuroendocrine component,
      and no ductules were observed. Although certain morphologic features of ductule
      containing endocrine tumors are reminiscent of the embryonic development of the
      human pancreas, none of the tumors expressed PDX-1, a transcription factor
      essential in pancreatic organ development. Based on our results, it is suggested
      that the ductular component occasionally found in pancreatic endocrine tumors is
      the result of entrapment of preexisting nonneoplastic ductules and that the
      tumors are otherwise not distinctive from conventional pancreatic endocrine
      tumors. Although the phenomenon is rare, it is important to recognize and to
      distinguish these tumors from true mixed ductal-endocrine neoplasms, which are
      generally more clinically aggressive. "Pancreatic endocrine tumors with entrapped
      ductules" would be the preferred nomenclature since it better reflects the
      nonneoplastic nature of the ductules.

PMID- 15166677
TI  - Primary pulmonary paraganglioma: report of a functioning case with
      immunohistochemical and ultrastructural study.
AB  - We describe a case of primary pulmonary paraganglioma, a tumor that has not been
      reported in sufficient detail in previous literature. The patient was a 55-year
      old woman with hypertension accompanied by an elevated serum norepinephrine level
      (2651 pg/mL; normal 100-450 pg/mL). Computed tomography revealed a well
      circumscribed solid mass, 3.5 cm in diameter, located in the lower lobe of the
      left lung. In the lobectomy specimen, the tumor had invaded the B8 bronchus and
      hilar lymph nodes with microscopic metastasis to the mediastinal nodes. The tumor
      showed histologic, immunohistochemical, and ultrastructural features of
      paraganglioma: argyrophilic cells arranged in a nesting (Zellballen) or
      anastomosing trabecular pattern within an arcuate vascular network. Neoplastic
      chief cells positive for neuroendocrine markers (CD56, synaptophysin,
      chromogranin A) were surrounded by sustentacular cells positive for S-100
      protein. Neurofilament protein was positively stained, but cytokeratins were
      totally negative. On electron microscopy, chief cells possessed abundant dense
      core granules with an eccentric halo ("norepinephrine-type" granules). The
      patient's blood pressure began to decline soon after the resection, and her serum
      norepinephrine promptly returned to almost normal. On the basis of our
      experience, our case is a bona fide primary pulmonary paraganglioma, a tumor
      heretofore subject to considerable skepticism.

PMID- 15166678
TI  - Placental site trophoblastic tumor in a late recurrence of a nonseminomatous germ
      cell tumor of the testis.
AB  - Placental site trophoblastic tumor (PSTT) is a well-defined entity in the female
      genital tract. In the male genital tract, a single case of PSTT in the testis of
      a young boy has been reported. Despite its very rare occurrence, PSTT of the
      testis has been incorporated in the latest WHO classification of tumors of the
      male genital tract. In this article, a case of a PSTT in a late retroperitoneal
      recurrence of a testicular nonseminomatous germ cell tumor in an adult male
      patient is presented. The tumor was discovered due to an elevated serum level of
      beta-human chorionic gonadotropin 4 years after chemotherapy. Upon review of the
      primary testicular tumor, small foci of intermediate trophoblastic tumor cells
      were discerned. This case illustrates that tumor cells resembling intermediate
      trophoblastic cells may metastasize to regional retroperitoneal lymph nodes.
      Because of their resistance to chemotherapy, these cells may invade surrounding
      tissue in due time, acquiring the typical morphology of PSTT.

PMID- 15166679
TI  - Re: CDX2 homeotic gene expression in gastric noninvasive neoplasia.

PMID- 15166681
TI  - Re: Non-B, non-T neoplasms with lymphoblast morphology: further clarification and
      classification.

PMID- 15166683
TI  - Effects of methylphenidate on attention deficits after traumatic brain injury: a
      multidimensional, randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the effects of methylphenidate on a variety of aspects of
      attention, ranging from laboratory-based impairment measures to caregiver ratings
      and work productivity, in individuals after traumatic brain injury. DESIGN: A
      total of 34 adults with moderate to severe traumatic brain injury and attention
      complaints in the postacute phase of recovery were enrolled in a 6-wk, double
      blind, placebo-controlled, repeated crossover study of methylphenidate,
      administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of
      attentional measures was gathered weekly, including computerized and paper-and
      pencil tests of attention, videotaped records of individual work in a distracting
      environment, real-time observational scoring of attentiveness in a classroom
      environment, and caregiver and clinician rating scales of attentiveness.
      Participants also attempted to guess their drug condition each week. Data from
      the first ten participants were used for pilot purposes, to develop attentional
      factors for composite scoring, and to identify attentional dimensions suggestive
      of a treatment effect for independent replication. The remaining 24 participants'
      results were used to confirm potential treatment effects seen in the pilot
      sample, using Wilcoxon's signed-ranks test on composite factor scores and
      individual variables. RESULTS: A total of 54 dependent variables were reduced to
      13 composite factors and 13 remaining individual variables. Of the 13 attentional
      factors, five showed suggestive treatment effects in the pilot sample. Of these,
      three showed statistically significant treatment effects in the replication
      sample: speed of information processing (effect sizes, -0.06 to 0.48; P < 0.001),
      attentiveness during individual work tasks (effect sizes, 0.15-0.62; P = 0.01),
      and caregiver ratings of attention (effect sizes, 0.44-0.50; P = 0.01). Of the
      individual variables, four showed suggestive treatment effects in the pilot
      sample, but only one showed significant treatment effects in the replication
      sample: reaction time before errors in the Sustained Attention to Response Task
      (effect size, 0.20; P = 0.03). No treatment-related improvement was seen in
      divided attention, sustained attention, or susceptibility to distraction. None of
      the variables showed suggestive or definite negative treatment effects. Effect
      sizes for those performance measures positively affected by methylphenidate were
      in the small to medium range and included both impairment and activity level
      measures. Improvements in processing speed did not seem to come at the expense of
      accuracy. CONCLUSIONS: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to
      individuals with attentional complaints after traumatic brain injury, seems to
      have clinically significant positive effects on speed of processing, caregiver
      ratings of attention, and some aspects of on-task behavior in naturalistic tasks.
      Further research is needed to identify the optimal dose and to extend these
      findings to less carefully selected individuals.

PMID- 15166685
TI  - Comparison of lorazepam and zopiclone for insomnia in patients with stroke and
      brain injury: a randomized, crossover, double-blinded trial.
AB  - OBJECTIVES: To determine if lorazepam or zopiclone is more effective in providing
      a restful night of sleep and to assess the effects of these medications on
      cognition. DESIGN: A randomized, double-blinded, crossover trial was performed at
      a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of
      18 brain-injured and stroke patients, aged 20-78 yrs, were administered
      lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75
      7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and
      characteristics of sleep were measured. Effects on cognition were also measured
      using the Folstein Mini Mental Status Exam. RESULTS: There was no difference in
      average sleep duration or in subjective measures of sleep. Cognition as assessed
      by the Mini Mental Status Exam revealed no difference in the zopiclone arm
      compared with the lorazepam arm. CONCLUSION: Zopiclone is equally effective as
      lorazepam in the treatment of insomnia in stroke and brain-injured patients.

PMID- 15166686
TI  - Electrophysiologic abnormalities of auditory and visual information processing in
      patients with traumatic brain injury.
AB  - OBJECTIVE: Through both auditory and visual modalities, we sought to explore the
      efficacy of event-related potentials in detecting residual cognitive impairments
      in patients with traumatic brain injury (TBI). DESIGN: Control subjects and TBI
      patients with favorable recovery were recruited. Pure tone and primary color
      discrimination tasks were utilized to elicit auditory and visual event-related
      potentials, respectively. All subjects were instructed to push a response button
      when they detected the target stimuli. Both behavioral and electrophysiologic
      responses were obtained simultaneously. We analyzed the event-related potential
      waveforms and examined the differences in amplitude, latency, behavioral reaction
      time, and response accuracy. RESULTS: A total of 11 TBI patients and 11 control
      subjects were tested. Results showed that (1) TBI patients had significantly
      lower P300 amplitude in both auditory (11.2 vs. 22. 7 microV) and visual (11.6
      vs. 20.9 microV) domains, (2) TBI patients had significantly longer P300 latency
      in both auditory (355 vs. 294 msecs) and visual (376 vs. 341 msecs) modalities,
      and (3) although there was no significant difference in response accuracy
      (97.7%vs. 100%), reaction time for both auditory and visual tasks were
      significantly longer in TBI patients (auditory, 404 vs. 277 msecs; visual, 397
      vs. 346 msecs). CONCLUSION: Although TBI patients with good recovery showed
      similar response accuracy when compared with control subjects, they demonstrated
      significantly poorer performance in both electrophysiologic and behavioral
      responses. Diminished amplitudes and prolonged latencies in P300 responses
      indicate impaired organization and categorization of incoming sensory
      information; prolonged behavioral reaction times suggest slowing in the response
      execution process. Clinical and theoretical implications and goals for continued
      research are discussed.

PMID- 15166687
TI  - Association of physical functioning with same-hospital readmission after stroke.
AB  - OBJECTIVE: Readmission after hospitalization for stroke is an important outcome.
      We sought to document the frequency of same-hospital readmission and to determine
      the relative value of physical functioning as a predictor of the outcome. DESIGN:
      Consenting patients (n = 228) who were admitted for ischemic stroke were
      characterized according to demographics, stroke severity, and self-reported
      prestroke and postadmission physical functioning. The hospital's administrative
      database was used to track readmissions during the year after index
      hospitalization. RESULTS: Same-hospital readmissions were experienced by 37.3% of
      the patients. The readmissions usually occurred within 100 days of discharge. The
      most common readmission diagnosis was stroke (14.1%). Lower prestroke and
      postadmission physical functioning (as reflected by dichotomous Barthel index
      scores) were weak but significant predictors of readmission (r = -0.165 and 
      0.268, respectively). Regression analysis showed that once postadmission physical
      functioning was accounted for, neither prestroke functioning nor any other
      measured variable added to the explanation of same-hospital readmission.
      CONCLUSION: The importance of physical functioning goes beyond rehabilitation. It
      is a potentially modifiable variable with implications for readmission.

PMID- 15166688
TI  - Natural history of chronic pain and pain treatment in adults with cerebral palsy.
AB  - OBJECTIVES: To determine if cerebral palsy-related pain and frequency of use of
      pain treatments change over time and to examine the association between use of
      pain treatments and changes in pain intensity. DESIGN: Longitudinal study of 50
      adults with cerebral palsy-related chronic pain, interviewed five times during
      the course of 2 yrs (6 mos between each interview). Subjects ranged in age from
      18 to 76 yrs old and included 25 women and 25 men. RESULTS: Pain intensity did
      not change significantly during the time period of the study (2 yrs), although
      there was a substantial increase in the frequency of use of several pain
      treatments from the initial to the second interview. Participants reported that
      many pain treatments were at least moderately helpful, but only three of the
      treatments (whirlpool, ultrasound, and transcutaneous electrical nerve
      stimulation) seemed to be associated with a decrease in pain among those who
      started using these treatments during the study. CONCLUSION: Pain does not seem
      to become systematically better or worse during the course of a 2-yr time period
      in adults with cerebral palsy-related pain. Although several pain treatments are
      reported to provide pain relief, many of these were rarely used by (or provided
      to) the study participants. There is a need for more research to determine which
      pain treatments are most helpful for cerebral palsy-related pain and to increase
      patient accessibility to effective pain treatments.

PMID- 15166689
TI  - Therapeutic selective nerve root block in the nonsurgical treatment of
      traumatically induced cervical spondylotic radicular pain.
AB  - OBJECTIVE: To investigate the outcomes resulting from the use of fluoroscopically
      guided therapeutic selective nerve root block in the nonsurgical treatment of
      traumatically induced cervical spondylotic radicular pain. DESIGN: Retrospective
      study with independent clinical review. A total of 15 patients who met specific
      physical examination or electrodiagnostic criteria and failed to improve
      clinically after at least 4 wks of physical therapy were included. Each patient
      demonstrated a positive response to a fluoroscopically guided cervical selective
      nerve root block. Therapeutic selective nerve root blocks were administered in
      conjunction with physical therapy. Outcome measures included visual analog scale
      pain scores, employment status, medication usage, and patient satisfaction.
      RESULTS: Patients' symptom duration before diagnostic injection averaged 13.0
      mos. An average of 3.7 therapeutic injections were administered. Follow-up data
      collection transpired at an average of 20.7 mos after discharge from treatment.
      An overall good or excellent outcome was observed in three patients (20.0%).
      Among those treated without surgery, a significant reduction (P = 0.0313) in pain
      score was observed at the time of follow-up. Six patients (40.0%) proceeded to
      surgery. CONCLUSIONS: These initial and preliminary findings do not support the
      use of therapeutic selective nerve root block in the treatment of this
      challenging patient population with traumatically induced spondylotic radicular
      pain.

PMID- 15166690
TI  - Association of sensorimotor function with knee joint kinematics during locomotion
      in knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the relationship between quadriceps sensorimotor function
      (knee joint-position sense, quadriceps strength, and quadriceps onset of
      activity) and knee joint kinematics (knee flexion at initial contact and loading)
      during level walking and stair descent in a large cohort of 220 people with knee
      osteoarthritis. DESIGN: Cross-sectional correlational study. RESULTS: Joint
      position sense correlated with knee flexion at initial contact during both tasks
      (r = -0.20 and -0.14, P <0.05). Strength correlated with peak loading response
      knee flexion during both tasks (r = 0.17 and 0.20, P < 0.05). Quadriceps onset
      correlated with knee flexion at initial contact during stair descent (r = 0.14, P
      < 0.05). Furthermore, differences in kinematic variables were observed when
      participants were divided into those with best and worst sensorimotor function.
      CONCLUSION: Impaired sensorimotor function as measured in this study is not
      strongly associated with altered knee joint kinematics observed in knee
      osteoarthritis patients during locomotion.

PMID- 15166692
TI  - Scheuermann's disease: the lumbar variant.

PMID- 15166693
TI  - Use of outcomes information in acute inpatient rehabilitation.
AB  - OBJECTIVE: To describe the ways in which rehabilitation outcomes information is
      used in the acute inpatient rehabilitation industry and the industry's views on
      the topic of public disclosure of rehabilitation outcomes information. DESIGN: A
      mixed-methods approach, featuring data from 39 informational telephone interviews
      with rehabilitation industry stakeholders followed by a survey of 95 randomly
      sampled acute inpatient rehabilitation provider organizations. RESULTS: Both the
      informational interviews and survey findings revealed that there is currently
      little stakeholder demand for functional outcomes information. Outcomes
      information is primarily used within provider organizations to track the
      effectiveness of rehabilitation services. There is general consensus among
      rehabilitation provider organizations in favor of public disclosure of outcomes
      information. CONCLUSIONS: Outcomes information is not routinely shared with
      rehabilitation stakeholders (i.e., payers and consumers). Rehabilitation
      providers and industry stakeholders generally express favorable attitudes toward
      public disclosure of outcomes information. Stakeholders' perceptions of current
      barriers and facilitators of outcomes information provide insight into the steps
      that can be taken toward greater transparency in the rehabilitation industry.

PMID- 15166694
TI  - Musculoskeletal injection skills competency in physical medicine and
      rehabilitation residents: a method for development and assessment.
AB  - An educational module was developed in attempt to satisfy two main objectives: to
      develop and implement a methodology for instruction of generally encountered
      injection techniques in the practice of physical medicine and rehabilitation and
      to implement an objective assessment format to measure attainment of these
      skills. Guidelines for this module were developed in consideration of
      Accreditation Council for Graduate Medical Education (ACGME) physical medicine
      and rehabilitation residency program requirements and ACGME Outcome Project.
      Eleven physical medicine and rehabilitation residents participated in a 1-day
      didactic/laboratory workshop covering injection education and techniques,
      followed by a supervised 2-wk practice session. Knowledge acquisition and skill
      attainment were measured via before and after multiple-choice written examination
      and simulated patient encounters utilizing anatomic models. An increase in
      knowledge was observed on the multiple-choice examination from pretest to
      posttest (pretest, 59.3%; posttest, 90.6%). Before instruction, 0 of 11 residents
      were able to perform any of the injection techniques (14 injection techniques and
      one sterile technique). At completion of the module, 7 of 11 residents (64%)
      competently performed 15 of 15 techniques (100%), 3 of 11 (26%) competently
      performed 14 of 15 techniques (93%), and 1 of 11 (9%) competently performed 11 of
      15 techniques (73%). Participation in this module resulted in substantial
      acquisition of knowledge and skills regarding musculoskeletal injections for
      physical medicine and rehabilitation residents. This workshop provided a
      framework for the definition of baseline competency in this clinical skill area.

PMID- 15166695
TI  - Prosthesis intolerance in patients with transfemoral amputation: a
      videocapillaroscopic study.
AB  - Videocapillaroscopy is a new technique allowing a noninvasive examination of the
      capillary framework of the skin by using a contact probe with magnifying lenses
      and a cold-light epiluminescence system. The aim of this article was to
      investigate, by videocapillaroscopy, the microcirculation of the skin of the
      stump in 70 consecutive patients with unilateral transfemoral amputation.
      Patients were divided into two subgroups according to their tolerance (A) or
      intolerance (B) to a prosthesis with an Icelandic-Swedish-New York socket.
      Subgroup A included 48 patients, 17 diabetic and 31 nondiabetic, and subgroup B
      included 22 patients, 16 diabetic and 6 nondiabetic. In subgroup B, the caliber
      of capillary loops was significantly larger (mean +/-standard deviation, 23.6 +/
      2.04 vs. 16.2 +/-1.96 microm; P < 0.001), neoangiogenesis was significantly more
      frequent (82%vs. 25%, P < 0.001), and the presence of microaneurysms (64%vs. 15%,
      P < 0.001) and microhemorrhages (36%vs. 4%, P < 0.001) was also more frequent.
      Surprisingly, some such diabetes-like microvascular changes were also found in
      the six nondiabetic patients of subgroup B. By using multiple logistic regression
      analysis, intolerance to the prosthesis was significantly related to
      microvascular changes (P = 0.001) but not to diabetes (P = 0.601), although
      diabetes was unequally distributed in the two subgroups.

PMID- 15166698
TI  - Is peace of mind a justifiable health claim?

PMID- 15166699
TI  - Political coverage.

PMID- 15166701
TI  - Heart failure.

PMID- 15166700
TI  - Political coverage.

PMID- 15166702
TI  - Lost and found.

PMID- 15166704
TI  - Injection technique.

PMID- 15166703
TI  - Therapy adherence.

PMID- 15166707
TI  - The AHA 'goes red' for women.

PMID- 15166710
TI  - Medicare's hidden price tag.

PMID- 15166712
TI  - HIV advances.

PMID- 15166713
TI  - The mirror has two faces.

PMID- 15166714
TI  - Exercise and COPD.

PMID- 15166715
TI  - Pain relief for neonates.

PMID- 15166718
TI  - What does it take to be called a nurse?

PMID- 15166716
TI  - Nurses' stress & burnout. How to care for yourself when caring for patients and
      their families experiencing life-threatening illness.

PMID- 15166719
TI  - A case for mistaken identity.

PMID- 15166731
TI  - First, do no harm. Avoiding the near misses.

PMID- 15166720
TI  - Medication selection by genotype: How genetics is changing drug prescribing and
      efficacy.

PMID- 15166732
TI  - The code of silence.

PMID- 15166736
TI  - Screening for obesity in adults: recommendations and rationale.

PMID- 15166738
TI  - Be aggressive toward violence.

PMID- 15166739
TI  - COSEHC overview.

PMID- 15166740
TI  - Highlights of the Tenth Annual COSEHC National Scientific Session.

PMID- 15166741
TI  - Bacteremia and infective endocarditis in patients on hemodialysis.
AB  - The number of patients with end-stage renal disease (ESRD) has risen dramatically
      over the last decade. There are 300,000 patients in the United States with ESRD
      who are receiving hemodialysis (HD), and the incidence is increasing at a rate of
      6% to 8% per year. Bacteremia, a prerequisite for infective endocarditis (IE),
      occurs at a rate of 0.7 to 1.4 episodes per 100 patient-care months. Few other
      medical conditions, except for chemotherapy-induced neutropenia,
      immunosuppression, and intravenous drug abuse, are associated with higher rates
      of bacteremia. IE occurs in approximately 2% to 6% of patients receiving HD. The
      aim of this article is to review the pathogenesis, diagnosis, current therapeutic
      options, and determinants of prognosis of IE in patients receiving HD.

PMID- 15166742
TI  - Occidental beriberi and sudden death.
AB  - Beriberi, thiamine deficiency, is classified as "dry" (neurologic) or "wet"
      (cardiovascular) and may be mixed. Deficiency of this vitamin may be nutritional
      or secondary to alcohol intoxication. In Western societies (occidental beriberi),
      the disorder is more commonly observed in long-term alcohol abusers. However, it
      may go undiagnosed because it is relatively uncommon. In some cases (acute
      cardiovascular beriberi), early treatment with parenteral vitamin B1 is required
      to prevent the development of low-output state and sudden death. We report a case
      of occidental beriberi with fatal outcome despite therapy.

PMID- 15166743
TI  - Deep sternal wound infection caused by group g streptococcus after open-heart
      surgery.
AB  - We report the first case of deep sternal wound infection caused by group G
      Streptococcus after open-heart surgery. The patient's clinical presentation was
      nonspecific and his diagnosis was delayed. Surgical debridement and a 4-week
      course of intravenous antibiotics consisting of sequential penicillin plus
      gentamicin/ceftriaxone led to recovery. Group G Streptococcus should be suspected
      as an important postoperative pathogen.

PMID- 15166744
TI  - Lymphangitis carcinomatosis of unknown origin presenting as severe pulmonary
      hypertension.
AB  - An apparently healthy 46-year-old woman was admitted because of progressive
      shortness of breath that had begun 2 months before her admission. Physical
      examination revealed a patient with respiratory distress, tachycardia, and mild
      jugular venous distention; otherwise, results were unremarkable. Our
      investigation revealed hypoxia and severe pulmonary hypertension with signs of
      right heart dysfunction, but no primary cause was found. The patient died 5 days
      after admission. Autopsy revealed pulmonary lymphangitis carcinomatosis caused by
      papillary carcinoma. No primary tumor was found.

PMID- 15166745
TI  - Tenosynovitis caused by Mycobacterium kansasii associated with a dog bite.
AB  - A 68-year-old man with adult-onset diabetes mellitus suffered an accidental
      puncture wound to the palm of his hand while playing with his pet dog. He
      received cephalosporin prophylaxis for 1 week. No inflammation occurred. Six
      months later, a mass developed near his elbow. It was removed. Histopathology
      revealed granulomas containing acid-fast bacilli (AFB). No culture was done.
      Swelling and decreased motion of the wrist and fingers developed. Magnetic
      resonance imaging revealed inflammation of the flexor compartment of the hand,
      wrist, and forearm. Surgical incision and drainage yielded purulent material,
      granulomatous inflammation, with AFB. Cultures yielded Mycobacterium kansasii.
      Several surgical procedures were required; M kansasii was recovered. He received
      isoniazid and rifampin for 1 year and prolonged rehabilitation. After 4 years, he
      was relatively asymptomatic, with good function of wrist and fingers. We believe
      this to be the first report of tenosynovitis caused by M kansasii in association
      with a dog bite.

PMID- 15166746
TI  - Diagnosis of malignant ascites in prostate cancer by measurement of prostate
      specific antigen.
AB  - We were confronted with a case of ascites in a man with known cirrhosis and
      advanced prostate cancer. Initial studies of ascitic fluid suggested cirrhosis as
      the cause of ascites. However, a prostate-specific antigen (PSA) study of ascitic
      fluid strongly suggested that the ascites was caused by prostate cancer.
      Subsequent cytologic studies confirmed malignant ascites. We suggest that
      measurement of PSA may be a valuable adjunctive study for the diagnosis of
      malignant effusions in prostate cancer.

PMID- 15166747
TI  - Acute hypercapnic respiratory failure due to thyrotoxic periodic paralysis.
AB  - Acute hypercapnic respiratory failure is a potentially life-threatening
      complication of profound hypokalemia usually seen in patients with large total
      body potassium (K+) deficits. It has rarely been reported in thyrotoxic periodic
      paralysis (TPP), which is due to intra-cellular shifts of K+. The authors report
      on a 29-year-old man who presented with sudden onset of muscle paralysis in all
      extremities and acute progressive respiratory insufficiency requiring artificial
      respiratory support. He was treated with intravenous KCl. After six hours,
      muscular strength had returned to normal, with plasma K+ concentration of 3.0
      mmol/L. At the eighth hour, rebound hyperkalemia (6.6 mmol/L) developed with high
      tented T waves, even after the KCl was discontinued. Ventilatory support was
      uneventfully weaned at 14 hours. Elevated free thyroxine and undetectable thyroid
      stimulating hormone confirmed the diagnosis of TPP. TPP should be kept in mind as
      a cause of acute respiratory failure in association with acute muscle weakness to
      avoid delayed diagnosis and improper management.

PMID- 15166748
TI  - Inadvertent rupture of an echinococcal cyst: case report and review of
      literature.
AB  - Echinococcal disease is infrequently seen in developed countries. In the United
      States, most cases are imported from endemic areas. Although frequently
      asymptomatic, enlarging cysts can cause local symptoms. Cysts can rupture
      spontaneously or as a result of trauma. Optimal management of accidental rupture
      of echinococcal cysts with little or no symptoms is not well known. The authors
      describe a case of inadvertent rupture of an echinococcal cyst and review the
      English literature to determine an acceptable management strategy.

PMID- 15166749
TI  - Atelectasis due to bronchial compression by the vertebral column.
AB  - The authors report the case of an 18-year-old woman with a multicore-minicore
      syndrome in acute respiratory distress. Initially, she was treated as having
      pneumonia, without a complete clinical response. Further investigation showed
      right lower lobe atelectasis associated with an extrinsic compression of the
      right mainstem bronchus secondary to thoracic lordoscoliosis. Therapeutic
      interventions involved respiratory therapy, noninvasive ventilation, cephalic
      traction, and orthopedic surgery, leading to clinical and functional improvement.

PMID- 15166750
TI  - Non-life-threatening sepsis: report of two cases.
AB  - Streptococcus bovis is one of the nonenterococcal species included among the
      streptococci group D. It is part of the normal bowel flora in humans and animals,
      but it is also responsible for infectious diseases (10-15% of all cases of
      bacterial endocarditis). Many cases of bacteremia and metastatic abscesses
      (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis
      were reported as associated with digestive tract diseases, mainly colonic
      disease, and, in particular colonic neoplasms, or chronic liver diseases. A role
      in carcinogenesis has been suggested for this microorganism. The authors report
      two cases of S. bovis sepsis, one associated with colonic neoplasm and the other
      with liver cirrhosis and gastric carcinoma. Discussion is focused on probable
      mechanisms that favor gastric colonization and systemic diffusion of S. bovis
      from the gut in patients with gastrointestinal neoplasms or chronic liver disease
      and provides clinical recommendations for patients with S. bovis infections.

PMID- 15166751
TI  - Polymorphoneutrophilic infiltration in acute interstitial nephritis of Sjogren
      syndrome.
AB  - Sjogren syndrome is a systemic autoimmune disease that involves the kidney as
      well as other organs. Tubulointerstitial nephritis secondary to monocyte,
      lymphocyte, and plasma cell infiltration is the characteristic lesion. The
      authors report a case of Sjogren related acute interstitial nephritis (AIN) with
      prominent neutrophilic infiltration in the interstitium. This is the first case
      describing predominance of neutrophilic infiltration in AIN associated with
      Sjogren syndrome.

PMID- 15166752
TI  - Aortic stenosis and autonomic dysfunction: co-conspirators in syncope.
AB  - Autonomic dysfunction and aortic stenosis share several clinical characteristics,
      including, in severe cases, syncope. Both illnesses tend to manifest later in
      life, and most cases are idiopathic in origin. In a short period of 4 weeks, the
      authors noted that three patients out of 36 referrals for autonomic dysfunction
      also had histories of aortic valve replacement due to stenosis. In each case,
      similar presenting symptoms of fatigue, light-headedness, and syncope were
      attributed to aortic stenosis without mention of autonomic failure as a possible
      contributor. The authors propose that patients for whom symptoms of aortic valve
      stenosis are not relieved by surgical intervention may have concomitant autonomic
      dysfunction contributing significantly to their symptoms. Furthermore, the two
      conditions may comprise a dangerous combination, aortic stenosis causing physical
      obstruction of ventricular outflow, and autonomic dysfunction causing decreased
      venous return and insufficient cardiac filling. It may be beneficial for patients
      with aortic stenosis who present with syncope to be considered for possible
      autonomic dysfunction to address both potential pathophysiologies contributing to
      the syncope.

PMID- 15166753
TI  - A mild form of Alstrom disease associated with metabolic syndrome and very high
      fasting serum free fatty acids: two cases diagnosed in adult age.
AB  - Alstrom syndrome (ALMS) is a very rare genetic autosomal recessive disease,
      characterized by early-onset severe abdominal obesity, impaired glucose tolerance
      or type 2 diabetes with insulin resistance, acanthosis nigricans, hyperlipidemia,
      childhood progressive retinal degeneration or retinitis pigmentosa and
      neurosensory hearing loss or deafness, cardiomyopathy, and other endocrine
      disorders. Genetic studies locate the ALMS gene on chromosome 2p12-13. The aim of
      this paper is to describe and discuss two unrelated cases of a mild ALMS form
      diagnosed after the age of 40 and 60, respectively, in adult fertile female
      patients. These cases showed several features of the disease plus other
      alterations characteristic of the classic "metabolic syndrome," including
      hypertension, hyperfibrinogenemia, and thrombotic states. Moreover, the patients
      had very high fasting serum free fatty acid (FFA) levels (2150 and 1919
      micromol/L, respectively), which proved to be sensitive to inhibition by oral
      glucose tolerance test (OGTT)-induced hyperinsulinemia as well as to caloric
      restriction. ALMS may have an adverse prognosis and is often underdiagnosed. Its
      mild form, which allows a long survival, may also be associated with the late
      complications of the metabolic syndrome, leading to increased vascular risk.

PMID- 15166755
TI  - Recurrence of pulmonary arteriovenous malformations in a female with hereditary
      hemorrhagic telangiectasia.
AB  - Pulmonary arteriovenous malformations (AVMs) are an uncommon disorder and may
      cause life-threatening complications if left untreated. The paucity of good
      longitudinal data on patients with pulmonary AVMs can be a significant challenge
      clinically. The authors report a case of recurrence of pulmonary AVMs in a young
      female with hereditary hemorrhagic telangiectasia (HHT) subjected to
      transcatheter embolotherapy (TCET) in 1995. Recurrence of pulmonary AVMs was
      suspected because of marked impairment of oxygenation in 1997 and in 2000, while
      the patient was pregnant, and later confirmed by imaging studies in early 2003.
      Despite successful embolization of all visible pulmonary AVMs, contrast
      echocardiography suggested the presence of intrapulmonary shunt. A shunt of 11.4%
      was measured using a 100% oxygen test. Loss of flow pattern was the immediate
      change of pulmonary AVMs after TCET shown by chest sonography. A decrease in the
      size of the pulmonary AVMs was observed 6 weeks later. This case illustrates the
      clinical relevance of longitudinal monitoring of arterial blood gases in
      screening for the recurrence of pulmonary AVMs, particularly in patients with
      HHT, and the roles of chest sonography and contrast echocardiography in
      monitoring the efficiency of TCET.

PMID- 15166754
TI  - Induction of testosterone metabolism by esomeprazole in a CYP2C19*2 heterozygote.
AB  - The authors describe a 42-year-old woman with previously normal sexual function
      who gradually developed loss of libido during treatment with esomeprazole. While
      taking esomeprazole, the patient's loss of libido improved with oral testosterone
      supplementation and deteriorated after testosterone withdrawal. There was steady
      improvement in both sexual function and serum free testosterone concentration
      after discontinuation of esomeprazole. Due to the temporal relationship between
      esomeprazole intake and sexual dysfunction, the authors postulate that
      esomeprazole causes induction of testosterone metabolism. The authors believe
      this to be the first case of female sexual dysfunction associated with
      esomeprazole described in the literature. They discuss a number of possible
      mechanisms for this effect.

PMID- 15166756
TI  - Measles encephalitis and acute pancreatitis in a young adult.
AB  - Although rare, encephalitis and hepatitis are major complications of measles that
      are more common in adults than in infants. On the other hand, although several
      other complications of measles, such as pneumonia and myocarditis, are found in
      all ages, acute pancreatitis in measles is very rare in both children and adults.
      We describe a 16-year-old female patient with measles encephalitis who developed
      acute pancreatitis. The response to steroid therapy was favorable.

PMID- 15166757
TI  - A biomechanical analysis of the causes of traumatic brain injury in infants and
      children.
AB  - There is significant disagreement among medical professionals regarding the
      mechanisms for infant brain injury. This disagreement is due in part to the
      failure by some to acknowledge and incorporate known biomechanical data and
      models into hypotheses regarding causes. A proper biomechanical understanding of
      the mechanisms of traumatic brain injury (TBI) challenges many published and
      testified assumptions regarding TBI in infants and children. This paper analyzes
      the biomechanical relationship between the causes of TBI in infants and children,
      and their physiological consequences. Loading characteristics, injury parameters
      and criteria, scaling, failure characteristics, differences between infants and
      adults, and impact due to falls are described and discussed in the context of the
      laws of mechanics. Recent studies are critiqued with reference to their
      contribution to an understanding of brain injury mechanisms. Finally, methods for
      improving our currently incomplete knowledge of infant head injuries, and their
      mechanisms, consequences and tolerances are proposed. There is an urgent need for
      close collaboration between physicians and biomechanicians to objectively and
      scientifically evaluate infant head injuries to further define their mechanical
      bases, and to assist in their diagnosis and treatment.

PMID- 15166759
TI  - Genetic diversity at 15 fluorescent-labeled short tandem repeat loci in the Patel
      and other communities of Gujarat, India.
AB  - Thirteen tetranucleotide and 2 pentanucleotide repeat units were analyzed in 120
      unrelated individuals of Patel and other communities of Gujarat, India. Allele
      frequency data obtained from the analysis of 15 short tandem repeat markers of
      the population were found to be satisfying Hardy-Weinberg equilibrium, with
      marginal deviations. Departures from Hardy-Weinberg equilibrium were observed in
      Patel communities at locus vWA and for that of the other communities at locus
      D7S820 and at locus TPOX. The power of discrimination values on an average fall
      within the range of 0.718 and 0.870, with deviations at locus D3S1358 showing a
      value of 0.400 for Patels. The value ranged between 0.709 and 0.869, with slight
      variations among the studied alleles in the other group. Thus, the 15 markers
      selected for this study were found to be highly suitable in human identification
      and for providing information on genetic polymorphism of the population of
      Gujarat.

PMID- 15166758
TI  - Suffocation in motor vehicle crashes.
AB  - Because death from suffocation in traffic fatalities has not been well described,
      we delineated the clinical, circumstantial, and autopsy findings associated with
      suffocation in a series of motor vehicle crashes. Medical examiner case files
      from a 5-year period were reviewed. Scene investigation, autopsy, toxicology, and
      first-responder reports were examined. Crash descriptions were reviewed,
      including vehicle type, mechanism of crash, response time, restraint use,
      occupant ejection, and victim position in cabins of vehicles. Mechanisms of
      suffocation, including torso compression, inversion, neck flexion, facial
      occlusion, and blood aspiration, were determined for each case. The files were
      searched for factors relevant to the diagnosis of suffocation, namely, cerebral
      concussion, alcohol intoxication, obesity, petechiae, lung weights as a proxy for
      livor, natural disease, and impact wounds. Twenty-nine traffic fatality cases
      were identified in which suffocation caused death. In 26, suffocation mechanisms
      were solely responsible for death. In 3, death was caused by suffocation in
      combination with other mechanisms. Twenty-five subjects were occupants of
      vehicles with cabins and 4 were motorcycle riders. The most common mechanism of
      suffocation was torso compression. Most subjects had either multiple mechanisms
      of suffocation or a single mechanism acting in concert with concussion or alcohol
      intoxication. Concussion and intoxication were common, with one or both present
      in 20 subjects, including all of those with blood aspiration. Petechiae were
      frequent but were found consistently only among those with inversion. Cutaneous
      chest petechiae were associated with inversion and torso compression. Lung
      weights were highest among those with blood aspiration and lowest among those
      with inversion. Body mass index was highest among those with inversion,
      suggesting that obesity could be a risk factor for this mechanism.

PMID- 15166760
TI  - Demonstration of a gastric bioptic specimen mix-up by laser capture
      microdissection (LCM) and DNA fingerprinting.
AB  - We demonstrate here the successful use of laser capture microdissection (LCM) and
      DNA fingerprinting in the identification of a case of gastric bioptic specimen
      mix-up. A 70-year-old man, suffering from chronic atrophic gastritis, underwent
      to a gastric biopsy and received a diagnosis of gastric cancer. In the absence of
      any clinical evidence of gastric cancer, a specimen mix-up was suspected. LCM was
      used to retrieve gastric cells from the histologic slide, classified as gastric
      carcinoma, and suspected to be mislabelled. DNA was extracted from microdissected
      cells, and a total of 16 different genetic loci were analyzed, using an identity
      test. Comparison of the results with those obtained using DNA extracted from a
      control slide, and from patient's saliva, demonstrated a distinct DNA fingerprint
      pattern in all genetic markers examined, clearly indicating the occurrence of a
      specimen mix-up. The combined use of LCM and DNA fingerprinting represents the
      most accurate and sophisticated method available for the identification of
      specimen mix-up, especially when only the tissue on the suspected slide is
      available.

PMID- 15166761
TI  - Unexpected hazard of illegal immigration: Outbreak of viral myocarditis
      exacerbated by confinement and deprivation in a shipboard cargo container.
AB  - We present a group of 18 illegal immigrant stowaways who arrived in a shipboard
      cargo container suffering from gastroenteritis, dehydration, and malnutrition and
      showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation
      included an evaluation of the 2-week ocean voyage, analysis of medical records
      and laboratory results of the survivors, autopsies on the decedents, and viral
      studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed
      lymphocytic myocarditis and 1 could not be evaluated histologically due to
      decomposition. A fourth stowaway died 4 months after arrival with dilated
      cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase
      chain reaction and nucleotide sequencing of viral isolates from the decedents'
      heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases
      represent an outbreak of viral myocarditis, exacerbated by acute dehydration and
      malnutrition, due to confinement within the shipping container. Our evidence
      indicates that close confinement promoted the spread of the virus, and
      nutritional deprivation increased the stowaways' vulnerability. Furthermore, our
      observations support the conclusion, based on experimental studies, that
      nutritionally induced oxidative stress increased the virulence of the etiologic
      viral agent. In summary, these cases represent a potential infectious disease
      hazard of illegal immigration.

PMID- 15166763
TI  - Characteristic features of deaths due to decapitation.
AB  - Deaths due to decapitation are rare in civilian populations. A study in South
      Australia over 17 years from January 1986 to December 2002 revealed 20 cases (age
      range, 14 to 72 years; average, 30.7 years; male to female ratio, 15:5). There
      were 13 suicides consisting of 11 train-related deaths (age range, 14 to 72
      years; average, 31.3 years; male to female ratio, 10:1), 1 hanging death, and 1
      death using a ligature and a motor vehicle. Five cases related to motor vehicle
      crashes (age range, 19 to 46 years; average, 30.2 years; male to female ratio,
      1:4) and 2 were associated with industrial trauma. Suicidal decapitation
      accounted for <1% of total suicides and showed a striking male predominance, with
      the favored method involving trains.

PMID- 15166762
TI  - Analysis of fatal injuries to motorcyclists by helmet type.
AB  - To clarify the characteristics of injuries of motorcyclists dying in accidents in
      relation to helmet type, we retrospectively analyzed forensic autopsies of 36
      helmeted motorcycle riders. The presence of major injuries and injury severity
      were evaluated with the injury severity score and the 1990 revision of the
      Abbreviated Injury Scale. Persons with open-face helmets (19 cases) were
      significantly more likely to have sustained severe head and neck injuries,
      especially brain contusions, than were persons with full-face helmets (17 cases).
      Furthermore, major injuries of the chest or abdomen, rib fractures, lung
      injuries, and liver injuries were each present in more than one quarter of all
      cases (26.3% to 70.6%), but their prevalences did not differ significantly
      between riders with different types of helmet. Because many types of head and
      neck injuries cannot be prevented and fatal chest and abdominal injuries occur
      despite the use of full-face helmets, more effective helmets and devices for
      protecting the chest and abdomen are needed to decrease deaths from motorcycle
      accidents.

PMID- 15166764
TI  - Postmortem production of ethanol and n-propanol in the brain of drowned persons.
AB  - We examined endogenous ethanol and n-propanol levels in the brain in 29 drowning
      cases in which ethanol consumption was excluded. Based on the stage of
      putrefaction of the brain, our cases were classified into 4 groups: pulpified
      brain (PB, n = 11), softened brain (SB, n = 6), discolored brain (DB, n = 2), and
      normal brain (NB, n = 10). The endogenous ethanol and n-propanol levels (mg/g),
      respectively, in the brains from these groups were 1.06 +/- 0.401 and 0.076 +/-
      0.032 in PB, 0.195 +/- 0.136 and 0.012 +/- 0.009 in SB, and 0.053 +/- 0.032 and
      0.001 +/- 0.001 in DB. Ethanol and n-propanol were not detected in NB. The
      concentration ratios of ethanol to n-propanol were 16.2 +/- 7.1 in specimens with
      ethanol levels > or = 0.50 mg/g (n = 10), and 17.6 +/- 13.5 in specimens with
      ethanol levels of 0.10 to 0.49 mg/g (n = 9). Drinking may strongly be suspected
      when (1) ethanol concentration in the brain is > or = 0.50 mg/g and cerebral
      ethanol to n-propanol ratio is > or = 40; and (2) the concentration of ethanol is
      0.10 to 0.49 mg/g and the ethanol to n-propanol ratio is > or = 60.

PMID- 15166765
TI  - Cardiovascular malformations and sudden death in infancy.
AB  - BACKGROUND: We survey the postmortem findings of cardiovascular malformations in
      infants under the age of 1 year who died suddenly and unexpectedly, in a way that
      mimicked sudden infant death syndrome (SIDS), and evaluate the importance of the
      malformation for the fatal outcome. METHODS: Four hundred fifty-seven infants
      under the age of 1 year, who died between 1982 and 2001, were investigated at the
      Department of Forensic Medicine in Stockholm, Sweden. RESULTS: Cardiovascular
      malformations were found in 18 infants (3.9%). Only 6 of 18 malformations, mostly
      severe, were clinically diagnosed before death. In the other 12 infants,
      cardiovascular malformations were found, such as atrial or ventricular septal
      defects, coarctation of aorta, stenosis of the aortic or pulmonary artery
      orifice, and aneurysm of the membranous portion of the interventricular septum.
      In all instances, the heart weight was increased. CONCLUSIONS: The observation of
      undiagnosed cardiovascular malformations as the only explanation for the cause of
      sudden and unexpected death in apparently healthy infants may advocate more
      examinations of the infant during early life. It is also important to enlarge the
      debate of the cause of death in infants with cardiovascular malformations. Should
      they be included in borderline SIDS?

PMID- 15166766
TI  - Medical malpractice: a study of case histories by the Forensic Medicine Section
      of Bari.
AB  - The learning objectives of this paper are to study the actual extent of medical
      malpractice, the medical acts at risk, and their impact on mortality. The number
      of suits filed against physicians for deaths resulting from alleged malpractice
      and autopsies ordered by the Judicial Authority in cases of possible therapeutic
      misadventures are rising. A major factor pushing this trend is public mistrust of
      healthcare providers and public and facilities. This mistrust is partly fueled by
      the mass media which, often to gain larger audience shares, sensationalizes
      single cases of real or alleged iatrogenic injury. Further, the potential for
      astronomic settlements, either from the single doctor or from the healthcare
      institution, has increased the number of legal proceedings that start on the
      basis of mere suspicion. In this context, the autopsy becomes an important
      instrument for shedding light on the situation, and it must be carried out by
      highly qualified and experienced professionals capable of ascertaining the cause
      of death, identifying any possible misconduct, and assessing its consequences. We
      reviewed the data regarding autopsies performed at the Forensic Medicine Section
      of the Department of Internal and Public Medicine of the University of Bari over
      1991 to 2000. We culled the cases alleged malpractice and, from these, identified
      those in which the death had truly been caused by medical error. This study also
      allowed us to understand the incidence of lethal therapeutic misadventures and to
      identify the medical and surgical branches more frequently involved.

PMID- 15166767
TI  - Medicolegal and ethical issues of cloning: do we need to think again and again?
AB  - Research on the cloning of human cells holds the promise of medical benefits, but
      cloning humans is a far more complex and ethically disturbing issue. Some have
      argued strenuously that human cloning should be banned permanently. They have
      called it immoral, repugnant, and abhorrent. Most European countries have already
      banned it, and others are considering a proscription. While allowing fundamental
      research in the field to progress, we need a wide debate on human cloning. We
      need to think about what, if any, circumstances might warrant cloning, as well as
      the circumstances under which it should never be allowed.

PMID- 15166768
TI  - Withholding and withdrawing of life support: a medicolegal dilemma.
AB  - The developments in medicine in general and the technology of life support in
      particular have provided the means of maintaining organ function for prolonged
      periods of time. However, there are many situations where life-sustaining
      treatment in an intensive care unit (ICU) may lead to a death with lingering and
      suffering of the patient, as well as burdening their family. Although often
      equated, withholding and/or withdrawing life-prolonging treatments that allow the
      patient to die needs to be differentiated from the physician-assisted suicides
      and euthanasia that involve the active ending of life. There is a difference
      between an unintended but accepted consequence of forgoing therapy and an
      intended result of death from suicide or euthanasia. The present-day physicians
      view most patient deaths as an inevitable process secondary to disorders
      unresponsive to treatment and/or multiple organ dysfunction syndromes. The large
      majority of patients dying in ICUs today succumb not after cardiopulmonary
      resuscitation, but rather, after the forgoing of life-sustaining treatment. Such
      approach has frequently caused families, institutions, and conservators of
      patients to resort to judicial fiat for resolution.

PMID- 15166769
TI  - Cerebrospinal fluid analysis in fatal thallium poisoning: evidence for delayed
      distribution into the central nervous system.
AB  - The neurologic manifestations of thallium poisoning include a severely painful
      ascending peripheral neuropathy, autonomic dysfunction, cranial nerve
      abnormalities, and a toxic encephalopathy. Although thallium has a short half
      life, these neurologic manifestations commonly progress, even as the blood
      concentration of thallium decreases. This suggests either that thallium persists
      in neuronal tissues or that it initiates an injury cascade that takes time to
      fully manifest. As the latter mechanism is consistent with many toxin exposures,
      the concept of a central nervous system reservoir for thallium is often
      discounted. A recent case provided a unique opportunity to evaluate this
      possibility. A 48-year-old man was acutely and chronically thallium poisoned by
      his common-law wife. During his initial exposures, only gastrointestinal symptoms
      manifested. Following an acute ingestion, hospitalization was required. Over 3
      days, his symptoms rapidly progressed from a severely painful neuropathy to
      slurred speech, ptosis, confusion, coma, respiratory insufficiency, and death.
      Because of considerations of alternative diagnoses, 2 lumbar punctures were
      performed, one on admission and another on the day of his death. Serum thallium
      concentrations obtained from stored blood samples were paired with spinal fluid
      concentrations from the same days. On day 1, serum and spinal fluid
      concentrations were 8700 mu/L and 1200 mu/L, respectively. On day 3, although the
      serum concentration had fallen to 7200 mu/L, the spinal fluid concentration had
      increased to 2100 mu/L. This case provides evidence to support the hypothesis
      that thallium distributes into the central nervous system more slowly than the
      blood compartment, and this may in part account for the progression of neurologic
      findings in the setting of decreasing serum concentrations.

PMID- 15166770
TI  - The insulin pump as murder weapon: a case report.
AB  - Microprocessor-controlled insulin pumps designed for continuous delivery of short
      acting insulin analogs into subcutaneous tissues offer several important
      potential benefits for diabetic patients. The delivery of other substances using
      these systems is technically feasible. We present a case of homicide involving
      lethal doses of etomidate and atracurium injected via the victim's insulin pump.
      This unique situation could be encountered by homicide investigators more
      frequently as the popularity of these systems continues to grow.

PMID- 15166772
TI  - Fatal impalement with transfixion of the neck in a road traffic accident.
AB  - The authors describe a singular case of fatal impalement due to penetration of a
      metal tube at the level of the neck in a victim of a road traffic accident. The
      man was traveling in the passenger seat ("death seat") of a car that hit the
      parapet of a bridge head on; death was attributed to hemorrhagic shock, which was
      brought on virtually instantly at the moment of impact.

PMID- 15166771
TI  - Sudden death following exercise testing related to abnormalities of the cardiac
      conduction system and coronary artery pathology.
AB  - A case of sudden death following exercise testing in a 33-year-old man is
      reported. The forensic autopsy showed atherosclerotic stenosis of the left
      coronary artery, as well as some changes in the cardiac conduction system,
      including anomalies of the atrioventricular node and moderate fibrosis and fatty
      infiltration of the branching bundle. This case demonstrates that cardiac arrest
      during vigorous exercise may be multifactorial and that abnormalities of the
      cardiac conduction system may have played some role in the fatal issue.

PMID- 15166773
TI  - Peculiar circular and C-shaped injuries on a body from the sea.
AB  - A case where a body with unusual circular injuries was found in the sea is
      presented. The victim was a 60-year-old woman who had been depressed and had
      attempted suicide before. She was missing for 6 days before the corpse was found.
      The body had several almost perfectly circular injuries and C-shaped incision
      injuries with almost circular flaps of skin. We concluded that the cause of the
      peculiar circular injuries might be bite marks of Isistius spp. (I. brasiliensis
      and/or I. plutodus), commonly known as cookie-cutter shark because of its very
      unusual feeding style.

PMID- 15166775
TI  - Death from spontaneous coronary artery dissection in a healthy postmenopausal
      woman.
AB  - Spontaneous dissection of the coronary arteries, in the absence of trauma, is an
      unusual but well-documented entity that occurs usually in middle-aged women. It
      is a rare cause of sudden death and myocardial infarction. Coronary eosinophilic
      arteritis is suggested to result in a predisposition to intimal disruption and
      dissection. We present the case of the sudden death of a previous healthy, 53
      year-old postmenopausal female, while working, in a town of Thessalia in Greece.
      The cause of death was left anterior descending coronary dissection with
      histologic findings of eosinophilic arteritis and autoimmune thyroiditis.

PMID- 15166774
TI  - Fatal olanzapine-induced hyperglycemic ketoacidosis.
AB  - Olanzapine is an antipsychotic medication linked to the development, or
      exacerbation of, type 2 diabetes mellitus. This report describes 3 patients being
      treated with olanzapine who died suddenly and unexpectedly with hyperglycemic
      ketoacidosis. All had olanzapine concentrations within the therapeutic range.
      Vitreous glucose concentrations ranged from 640 mg/dL to 833 mg/dL, and blood
      acetone concentrations from 25.6 mg/dL to 57.6 mg/dL. Beta-hydroxybutyrate
      concentrations in blood were from 55.2 mg/dL to 110 mg/dL. Low levels of
      isopropanol were also detected. None had a history or family history of diabetes
      mellitus. Glycolated (A1C) hemoglobin in 2 cases was 14.3% and 14.7%. No
      predisposing factors to olanzapine-induced diabetes were identified. It is
      recommended that chemical testing of patients dying suddenly while being treated
      with antipsychotic drugs include vitreous glucose and blood acetone
      determinations to elucidate the cause and mechanism of death in these patients.
      Warnings concerning this potentially fatal complication of olanzapine therapy
      should be included in standard pharmaceutical and prescription references.

PMID- 15166776
TI  - Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl
      from transdermal patches.
AB  - The transdermal fentanyl system delivers a specific dose at a constant rate. Even
      after the prescribed application time has elapsed, enough fentanyl remains within
      a patch to provide a potentially lethal dose. Death due to the intravenous
      injection of fentanyl extracted from transdermal patches has not been previously
      reported. We present 4 cases in which the source of fentanyl was transdermal
      patches and was injected. In all of these cases, the victim was a white male who
      died at home. Case 1 was a 35-year-old with no known history of drug use, who was
      found by his wife on the floor of his workshop. Police recovered a fentanyl
      patch, needle, and syringe at the scene. Case 2 was a 38-year-old with a known
      history of drug use whose family claimed that he was in a treatment program that
      used fentanyl patches for unknown reasons. His brother found him dead in bed, and
      law enforcement officers found a hypodermic needle beside the body; a ligature
      around his left hand, and apparent needle marks between his first and second
      digits were also noted. Case 3 was a 42-year-old with a recent attempted suicide
      via overdose who was found dead at his home. An empty box of fentanyl patches,
      Valium, Ritalin, and 2 syringes were found at the scene. Case 4 was a 39-year-old
      found by his mother, who admitted to removing a needle with attached syringe from
      the decedent's arm. Medications at the scene included hydrocodone, alprazolam,
      zolpidem, and fentanyl patches. All reported deaths were attributed to fentanyl
      intoxication, with blood concentrations ranging from 5 to 27 microg/L.

PMID- 15166777
TI  - Postmortem molecular analysis in victims of sudden unexplained death.
AB  - Among several conditions that can be responsible for sudden cardiac death (SCD),
      an important role is played by long QT syndrome (LQTS). LQTS is a congenital
      electric heart disease that can be asymptomatic or have very severe clinical
      manifestation, leading to cardiac arrest. In fact, the first manifestation of
      LQTS can be hyperkinetic ventricular arrhythmias. The presence of LQTS should be
      considered in all cases of SCD where autopsy is negative for anatomic and
      histopathological findings. In these cases, after an accurate anamnesis, a
      genetic screening should always be performed. The screening on LQTS genes is
      performed on DNA extracted from paraffin-embedded tissues. Making a proper
      diagnosis in such cases can help to find new affected subjects among the family
      members of SCD victims and treat them. In these cases, if the pathologist does
      not make a correct diagnosis, can he or she be sued for malpractice?

PMID- 15166778
TI  - The role and mode of action of apolipoproteins CIII and AV: synergistic actors in
      triglyceride metabolism?
AB  - PURPOSE OF REVIEW: Apolipoprotein (apo)CIII and apoAV play an important role in
      triglyceride metabolism as evidenced by the unambiguous and opposing phenotypes
      of transgenic and knockout mouse models. In this review we discuss studies on the
      genetics, protein structure, and regulation of apoCIII and apoAV and compare
      their potential molecular mechanisms of action in triglyceride metabolism. We
      examine the hypothesis that apoCIII and apoAV synergistically affect triglyceride
      metabolism. RECENT FINDINGS: It has now been firmly established that variation in
      plasma triglyceride levels in a wide range of human populations is strongly
      associated with genetic variation at the chromosomal locus encoding both the
      APOC3 and APOA5 genes, the APOA1/C3/A4/A5 gene cluster. The close physical
      linkage of these genes and the frequent concurrence of genetic variants, however,
      complicate the assignment of specific metabolic defects to specific
      polymorphisms. Recent insight into the regulation of APOC3 and APOA5 gene
      expression and structural modeling studies on the apoAV protein have provided
      novel clues for the potential molecular mechanisms responsible for the effects of
      apoCIII and apoAV on triglyceride metabolism. SUMMARY: Hypertriglyceridemia is a
      major independent risk factor in the development of cardiovascular disease.
      Moreover, triglyceride-derived fatty acids are thought to play a key role in the
      development and progression of the metabolic syndrome. As modulators of
      triglyceride metabolism, apoCIII and apoAV are key players and potential
      therapeutic targets. However, little is known of their molecular mechanism and
      potential cooperativity. Rational therapeutic application will require the
      filling of this hiatus in our knowledge.

PMID- 15166779
TI  - Apolipoprotein A-II, genetic variation on chromosome 1q21-q24, and disease
      susceptibility.
AB  - PURPOSE OF REVIEW: Apolipoprotein (apo) A-II is the second most abundant HDL
      apolipoprotein; however its function remains largely unknown. Owing to the lack
      of consequences of apoA-II deficiency in humans, it has long been considered an
      apolipoprotein of minor importance. Overexpression of apoA-II in transgenic mice,
      however, causes combined hyperlipidemia and, in some cases, insulin resistance.
      This, and the location of the apoA-II gene in chromosome 1q23, a hot region in
      the search for genes associated with familial combined hyperlipidemia, insulin
      resistance and type 2 diabetes mellitus, has greatly increased interest in this
      protein. RECENT FINDINGS: ApoA-II is biochemically and genetically linked to
      familial combined hyperlipidemia. Given that the chromosome 1q21-q24 region is
      associated with insulin resistance or type 2 diabetes, this region is a now a
      focus of interest in the study of these complex, often overlapping diseases.
      However, no polymorphisms that increase apoA-II levels have been identified to
      date in humans. Other nonstructural loci may regulate apoA-II plasma
      concentration. Further, plasma apoA-II concentration is increased by saturated
      fat intake. Several reports have added to our understanding of the relationship
      between apoA-II mutations and amyloidosis both in humans and mice. SUMMARY: An
      increased plasma concentration of apoA-II might contribute to familial combined
      hyperlipidemia or type 2 diabetes mellitus expression, which emphasizes the need
      to understand its function and metabolism. Genetic studies in well characterized
      patients and genomic and proteomic approaches in cell and mouse models may help
      to achieve this understanding.

PMID- 15166780
TI  - Emerging roles for phospholipid transfer protein in lipid and lipoprotein
      metabolism.
AB  - PURPOSE OF REVIEW: This review highlights the recent key advances in our
      understanding of the role of phospholipid transfer protein in lipid and
      lipoprotein metabolism. RECENT FINDINGS: The overexpression of human phospholipid
      transfer protein in mice is associated with an increase in atherosclerosis. This
      is consistent with earlier studies using mouse models suggesting that
      phospholipid transfer protein was pro-atherogenic. The presence of phospholipid
      transfer protein in macrophages and atherosclerotic lesions suggests that it
      could be either anti-atherogenic by facilitating lipid efflux or pro-atherogenic
      by facilitating lipid retention. Phospholipid transfer protein may also be a key
      player in reverse cholesterol transport, as it interacts with the adenosine
      triphosphate-binding cassette transporter A1 and facilitates lipid efflux from
      peripheral cells. Both the release of chymase, a neutral protease, from mast
      cells and the oxidation of HDL by hypochlorous acid can impair the function of
      phospholipid transfer protein in reverse cholesterol transport. Studies of
      phospholipid transfer protein-mediated phospholipid transfer activity in humans
      support a role for phospholipid transfer protein in hypertriglyceridemia,
      obesity, diabetes, inflammation and coronary artery disease, and in the
      modulation of LDL particle density and size. Furthermore, recent evidence
      suggests that phospholipid transfer protein may play a role in reproductive
      processes, in lipid and lipoprotein metabolism in the central nervous system, and
      in neurodegenerative disease. SUMMARY: Phospholipid transfer protein is emerging
      as a multifaceted and multifunctional player in lipid and lipoprotein metabolism,
      but much additional work will be required to understand the significance of these
      recent findings for clinical practice.

PMID- 15166781
TI  - Paraoxonase, a cardioprotective enzyme: continuing issues.
AB  - PURPOSE OF REVIEW: The paraoxonase family consists of three members (PON1, PON2
      and PON3) that share structural properties and enzymatic activities, among which
      is the ability to hydrolyze oxidized lipids in LDL. The exact function of the
      different family members is not clear although the conservation among the
      individual family members across species suggests a strong evolutionary pressure
      to preserve these functional differences. The purpose of this review is to
      highlight several problems with respect to the mechanism of action of paraoxonase
      and differences between the family members that merit further study. RECENT
      FINDINGS: PON1 transgenic mice are at lower risk for atherosclerosis, which is
      consistent with PON1 gene knockout studies in mice and human genetic polymorphism
      studies. The exact mechanism by which paraoxonase is cardioprotective is not
      clear, although it is likely to be related to its antioxidant properties
      especially on LDL. PON1 levels are influenced by a variety of environmental
      factors, including statins and cytokines. The preferential association of PON1
      with HDL is mediated in part by its signal peptide and by desorption from the
      plasma membrane of expressing cells by HDL or phospholipid. Apolipoprotein A-I is
      not necessary for PON1 association with HDL, but its activity is stabilized in
      the presence of the apolipoprotein. Only in the absence of both lecithin
      cholesterol acyltransferase and apolipoprotein E is paraoxonase associated with
      non-HDL lipoproteins. The displacement of paraoxonase by serum amyloid A may
      explain in part the proinflammatory nature of HDL in the acute phase. The
      mechanism by which PON3 associates with HDL has not been studied. In addition to
      the ability to hydrolyze oxidized lipids in LDL, paraoxonase also alters the
      oxidative state of macrophages. Exogenous PON1 is able to reverse the oxidative
      stress in macrophages in aged apolipoprotein E deficient and PON1 deficient mice.
      The increase in oxidative stress in macrophages from PON1 deficient mice occurs
      despite the expression of PON2 and PON3 in macrophages. PON1 has recently been
      shown to contain phospholipase A2 activity, with the subsequent release of
      lysophosphatidylcholine that influences macrophage cholesterol biosynthesis.
      SUMMARY: PON1 mass and activity in the plasma significantly influence the risk of
      developing cardiovascular disease. This is likely mediated by its antioxidation
      properties on LDL and/or macrophages. The precise mechanism by which this HDL
      associated protein prevents or attenuates oxidation of LDL and the oxidative
      stress of macrophages remains to be clarified. The role of PON2 and PON3 in
      atherosclerosis and their antioxidant properties with respect to LDL and
      macrophages also merit further investigation.

PMID- 15166782
TI  - High density lipoproteins in the intersection of diabetes mellitus, inflammation
      and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Low HDL-cholesterol, diabetes mellitus and elevated C-reactive
      protein as well as various inflammatory diseases are risk factors for coronary
      heart disease. Both diabetes mellitus and inflammation decrease HDL-cholesterol.
      We summarize recent findings on the mechanisms underlying low HDL-cholesterol in
      diabetes and inflammation, as well as on novel functions of HDL that may protect
      not only from atherosclerosis but also from diabetes mellitus and inflammation
      induced organ damage. RECENT FINDINGS: Elevated levels of non-esterified fatty
      acids and disturbed insulin action contribute to low HDL-cholesterol in diabetes
      mellitus by modifying lipolysis, apolipoprotein A-I production, as well as the
      activities of adenosine triphosphate-binding cassette transporter A1 and lipid
      transfer. Inflammation causes low HDL-cholesterol by increasing the activities of
      endothelial lipase and soluble phospholipase A2 and by replacing apolipoprotein A
      I in HDL with serum amyloid A. HDL and lysosphingolipids therein have been
      identified as activators of the protein kinase Akt, which in turn is a regulator
      of apoptosis in beta-cells, endothelial cells, and smooth muscle cells, as well
      as a regulator of nitric oxide production and adhesion molecule expression in
      endothelial cells. SUMMARY: The protective properties of HDL in cytokine
      production, lipid oxidation, cholesterol efflux and reverse cholesterol transport
      make HDL a protective agent in inflammation-induced organ damage including
      diabetes mellitus. However, inflammation and diabetes cause a decrease in HDL
      cholesterol concentrations and impair HDL function, placing HDL into the centre
      of a vicious cycle that may escalate into diabetes mellitus, inflammation-induced
      organ damage and atherosclerosis.

PMID- 15166783
TI  - Hepatic cholesterol transport from plasma into bile: implications for gallstone
      disease.
AB  - PURPOSE OF REVIEW: The transhepatic traffic of cholesterol from plasma
      lipoproteins into the bile is critical for overall cholesterol homeostasis and
      its alterations may lead to cholesterol gallstone formation. This review
      summarizes recent progress in understanding the key hepatic cholesterol
      metabolism-related proteins and pathways that influence biliary secretion of
      cholesterol. RECENT FINDINGS: In cholesterol-fed apolipoprotein E knockout mice,
      the availability of dietary cholesterol for biliary disposal is decreased and
      diet-induced gallstone formation is impaired. Scavenger receptor class B type I
      is relevant for cholesterol transport from plasma HDL into the bile in chow-fed
      mice, however its expression is not critical for biliary cholesterol secretion
      and gallstone formation in lithogenic diet-fed mice. Intrahepatic cholesterol
      transport proteins (e.g. sterol carrier protein-2, Niemann Pick type C-1 protein)
      also determine liver cholesterol available for biliary secretion in mice. Genetic
      manipulation of canalicular ATP-binding cassette transporter G5 and G8 expression
      in mice has established their essential role for biliary cholesterol secretion.
      SUMMARY: Recent studies have underscored that different proteins involved in
      hepatic cholesterol transport regulate the availability of cholesterol for
      biliary secretion. These advances may provide new avenues for prevention and
      treatment of various disease conditions linked to abnormal cholesterol
      metabolism.

PMID- 15166784
TI  - Scavenger receptor BI: a scavenger receptor with a mission to transport high
      density lipoprotein lipids.
AB  - PURPOSE OF REVIEW: This review will survey recent findings on the cholesterol
      transport and scavenger functions of scavenger receptor BI. Although scavenger
      receptor BI and CD36 bind many of the same ligands, these two receptors have very
      specific lipid transport functions: CD36 facilitates the uptake of long chain
      fatty acids and SR-BI mediates the transport of cholesterol and cholesteryl ester
      from HDL particles. Scavenger receptor BI is a physiologically relevant HDL
      receptor that, along with HDL, is protective against cardiovascular disease. Its
      atheroprotective role has been hypothesized to be due to its function in the
      reverse cholesterol transport pathway. RECENT FINDINGS: Recent studies suggest
      that scavenger receptor BI function is not only crucial for cholesterol delivery
      to the liver but is also important for cholesterol efflux at the vessel wall.
      Therefore, the receptor acts at both ends of the reverse cholesterol transport
      pathway. In addition, it stimulates nitric oxide production in endothelial cells,
      which may also contribute to its positive influence on the vasculature. Lastly,
      the glycoprotein was cloned as a scavenger receptor and in some cases is still
      thought to operate in this fashion. SUMMARY: It will be interesting to follow
      future research on scavenger receptor BI that will delineate its functions in
      cholesterol transport as well as its scavenger functions. Additionally, we are
      only beginning to learn of the glycoprotein's effects on disease states besides
      atherosclerosis and cardiovascular disease.

PMID- 15166785
TI  - Regulation of insulin sensitivity by adipose tissue-derived hormones and
      inflammatory cytokines.
AB  - PURPOSE OF REVIEW: The aim of this review is to assess the role of adipose tissue
      derived hormones and inflammatory cytokines in the pathogenesis of obesity-linked
      type II diabetes, with a special focus on articles published between December
      2002 and December 2003. RECENT FINDINGS: Insulin resistance is widely recognized
      as a fundamental defect seen in obesity and type II diabetes. Although the
      molecular mechanisms triggering the development of insulin resistance remain
      elusive, recent studies have suggested that adipose tissue and adipose tissue
      derived hormones and inflammatory cytokines play essential roles in the overall
      insulin sensitivity in vivo. Dysfunctions of adipose tissue can lead to systemic
      insulin resistance. SUMMARY: Understanding the regulation of the metabolic and
      secretory functions of adipose tissue, as well as its subsequent impact on
      overall insulin sensitivity, is becoming increasingly important given the
      therapeutic potential of targeting the root causes of insulin resistance in the
      treatment of type 2 diabetes and its associated complications, such as
      cardiovascular and cerebrovascular diseases.

PMID- 15166786
TI  - New insights into inhibitors of adipogenesis.
AB  - PURPOSE OF REVIEW: Adipose tissue is a dynamic organ that changes mass throughout
      life in response to the metabolic needs of the animal. In the past three decades,
      significant advances have been made in delineating key extracellular and
      intracellular stimulators of fat cell formation or adipogenesis. In this review,
      the author focuses on new findings of specific inhibitors of adipogenesis.
      Understanding the balance between positive and negative regulators of
      adipogenesis has important health-related implications for anti-obesity medical
      therapy and lipodystrophy. RECENT FINDINGS: Adipogenesis is a highly regulated
      process requiring coordinated expression and activation of two main groups of
      adipogenic transcription factors, CCAAT/enhancer binding proteins and peroxisome
      proliferators activated receptor gamma. In response to hormonal and nutrient
      stimuli, the increased expression and activation of these transcription factors
      induce the expression of adipocyte-specific genes. More recently, several groups
      have identified extracellular inhibitors of adipocyte formation, including
      cytokines, lipid molecules, genistein, and protease inhibitors. Intracellular
      signaling molecules, which negatively regulate adipogenesis, include Pref-1,
      Foxo1, Foxa2, SMAD-3, WNT-10b, GATA-2 and GATA-3. SUMMARY: The prevalence of
      obesity is increasing in the United States and in other westernized societies.
      Understanding the mechanisms of excessive energy storage in adipose tissue is
      necessary to develop a comprehensive strategy to prevent and treat obesity. One
      potential, but unrealized, approach to obesity treatment is to target excessive
      adipose tissue enlargement. A number of promising extra- and intracellular
      inhibitors of fat cell formation have been identified, but the modulation of
      adipose tissue mass may have both advantageous and deleterious health effects.

PMID- 15166787
TI  - Regulation of fatty acid transport.
AB  - PURPOSE OF REVIEW: The aim of the present review is to summarize recent
      developments in the area of regulation of fatty acid transport. RECENT FINDINGS:
      While controversy still exists regarding the contribution of passive diffusion
      versus protein-mediated fatty acid transport, both processes are now widely
      accepted. With the recent identification of an increasing number of putative
      fatty acid transporters, emphasis has been placed on regulation including fatty
      acid transport function of the protein, and also possible associated functions
      (acylCoA synthase activity and vectorial channelling to intracellular
      processing). Deciphering these issues has been facilitated through the use of
      loss-of-function (such as knockout) and gain-of-function (cell transfectants and
      transgenic mice) models. SUMMARY: It is likely that our concept of fatty acid
      transport will continue to converge, incorporating the individual functions of
      the wide variety of fatty acid transporters into an integrated physiologic
      framework with relevance to a number of diseases.

PMID- 15166788
TI  - Role of leptin in reproduction.
AB  - PURPOSE OF REVIEW: This article focuses on recently gained knowledge concerning
      the different emerging aspects of the role of leptin in reproduction, through
      both its central hypothalamus-mediated and peripheral actions. RECENT FINDINGS:
      As delineated in murine models, STAT3-independent signals triggered by the leptin
      receptor are clearly important in fertility, and candidate pathways such as those
      via phosphatidylinositol-3 kinase and extracellular signal-related kinase are
      implicated in leptin-regulated cascades. Another aspect whose importance has
      recently been revealed is that of the bioavailability of leptin in general, and
      the fate and action of carrier-bound versus free leptin at central and peripheral
      sites in particular. SUMMARY: Besides the well-established role of leptin in the
      control of appetite and energy expenditure in humans and animals, evidence for a
      major involvement of the hormone in the function of the reproductive system is
      rapidly accumulating through physiological and molecular genetic approaches.
      Powerful animal models that facilitate the dissection of increasingly complex
      pathways, together with detailed studies in man, will soon delineate in detail
      the diverse roles of leptin in biological regulation. The development of
      therapeutic agents primarily directed against obesity must therefore take into
      consideration the consequences of treatment not only on the amelioration of
      leptin resistance, but also on the bioactivity of leptin in the context of
      growth, glucose homeostasis, and last but not least, fertility.

PMID- 15166789
TI  - Oxysterol binding protein and its homologues: new regulatory factors involved in
      lipid metabolism.
AB  - PURPOSE OF REVIEW: Oxysterol binding protein was discovered in the 1980s as a
      cytosolic high-affinity receptor for oxysterols, but its function has remained
      enigmatic. Families of genes/proteins with sequence homology to oxysterol binding
      protein have been identified in eukaryotes from yeast to man, indicating that
      these proteins, denoted as oxysterol binding protein-related proteins (ORPs),
      serve a fundamental purpose conserved in evolution. This review discusses recent
      findings that provide important clues to the mode of action of these proteins.
      RECENT FINDINGS: The long variant of ORP1 is induced upon differentiation of
      monocytes to macrophages and has capacity to enhance the trans-activation
      potential of liver X receptors, indicating a function in macrophage lipid
      metabolism. Important clues to ORP function were provided by the finding that
      most family members carry an endoplasmic reticulum targeting motif, while the
      amino-terminal regions of the proteins have targeting specificities for other
      organelles. Extensive splice variation occurs within the gene family, suggesting
      that a large number of distinct protein products are encoded. Further
      implications were obtained for a possible role of a family member in tumor cell
      metastasis. SUMMARY: ORPs constitute a novel family of proteins implicated in
      cellular lipid metabolism and different aspects of cell regulation. The function
      of several family members is connected with cellular sterol metabolism, and there
      is evidence for a role of oxysterol binding protein in lipid transport from the
      endoplasmic reticulum. Recently, a model on the function of these proteins at
      membrane contact sites, specialized zones of communication between two different
      organelles, has been presented.

PMID- 15166790
TI  - Electronegative low-density lipoprotein.
AB  - PURPOSE OF REVIEW: The occurrence in blood of an electronegatively charged LDL
      was described in 1988. During the 1990s reports studying electronegative LDL
      (LDL(-)) were scant and its atherogenic role controversial. Nevertheless, recent
      reports have provided new evidence on a putative atherogenic role of LDL(-). This
      review focuses on and discusses these new findings. RECENT FINDINGS: In recent
      years, LDL(-) has been found to be involved in several atherogenic features
      through its action on cultured endothelial cells. LDL(-) induces the production
      of chemokines, such as IL-8 and monocyte chemotactic protein 1, and increases
      tumor necrosis factor-alpha-induced production of vascular cell adhesion molecule
      1, with these molecules being involved in early phases of leukocyte recruitment.
      LDL(-) from familial hypercholesterolemic patients also decreases DNA synthesis
      and intracellular fibroblast growth factor 2 production, which may contribute to
      impaired angiogenesis and increased apoptosis. In addition, the preferential
      association of platelet-activating factor acetylhydrolase with LDL(-) has been
      reported, suggesting a proinflammatory role of this enzyme in LDL(-). SUMMARY:
      Recent findings suggest that LDL(-) could contribute to atherogenesis via several
      mechanisms, including proinflammatory, proapoptotic and anti-angiogenesis
      properties. Further studies are required to define the role of LDL(-) in
      atherogenesis more precisely and to clarify mechanisms involved in endothelial
      cell activation.

PMID- 15166791
TI  - Platelet-activating factor acetylhydrolase: is it good or bad for you?
AB  - PURPOSE OF REVIEW: Although findings obtained from various studies are
      inconclusive in determining whether plasma platelet-activating factor
      acetylhydrolase, or lipoprotein-associated phospholipase A2, plays a
      proatherogenic or antiatherogenic role in atherosclerosis, many recent reviews
      appear to favor it as a risk factor for coronary artery disease. To provide a
      contrasting view, this review focuses on the enzyme's antiatherogenic and
      antiinflammatory properties. RECENT FINDINGS: A recent report demonstrates that
      plasma platelet-activating factor acetylhydrolase activity increases in men and
      women with stable angina or acute coronary syndromes, supporting previously
      published data that plasma levels of the protein are independently and positively
      associated with the risk of coronary artery disease. In contrast, at least four
      lines of evidence indicate that the enzyme has strong antiatherogenic properties:
      (1) it inhibits the effects of LDL oxidation, (2) genetic deficiency of plasma
      levels constitutes a risk factor for vascular diseases including atherosclerosis,
      (3) adenoviral transfer of the protein reduces atherosclerosis in apolipoprotein
      E-deficient mice, and (4) pretreatment of an electronegative LDL subfraction
      isolated from hypercholesterolemic human plasma with a recombinant platelet
      activating factor acetylhydrolase completely abolishes the proapoptotic effects
      of the electronegative LDL on vascular endothelial cells. Additionally, treatment
      with the recombinant product reduced mortality from severe sepsis in a phase IIb
      clinical trial. In an animal study, transfection of tumor cells with platelet
      activating factor acetylhydrolase inhibited tumor growth at the site of
      implantation. SUMMARY: Plasma platelet-activating factor acetylhydrolase becomes
      progressively activated as atherosclerosis progresses, but lines of evidence
      indicate that the enzyme possesses potent antiatherogenic and antiinflammatory
      properties. This raises the question of whether increased activity is a cause or
      a result of atherosclerosis and, consequently, whether inhibiting the enzyme's
      activities may decelerate or accelerate the progress of the disease.

PMID- 15166792
TI  - Bibliography. Current world literature. Lipid metabolism.

PMID- 15166793
TI  - Nutrition and therapeutics.

PMID- 15166794
TI  - LRP5, a multifunctional cell surface receptor.

PMID- 15166795
TI  - C-reactive protein: a surrogate marker for atherosclerosis.

PMID- 15166796
TI  - The role of antioxidant therapy in cardiovascular disease.

PMID- 15166797
TI  - Of cholesterol-free mice and men.

PMID- 15166798
TI  - Therapy and clinical trials.

PMID- 15166801
TI  - Metabolic syndrome: the new cardiovascular target.

PMID- 15166802
TI  - Genes, diet and serum lipid concentrations: lessons from ethnically diverse
      populations and their relevance to coronary heart disease in Asia.
AB  - PURPOSE OF REVIEW: The burden of coronary heart disease (CHD) in Asia has risen
      in tandem with socio-economic development and urbanization. Although all ethnic
      groups have been affected, some appear to be at particularly high risk. The basis
      of these ethnic differences remains poorly understood. RECENT FINDINGS: Differing
      levels of risk factors for CHD have been observed between ethnic groups. Previous
      studies, however, may be confounded by a large ethnic variation in socio-economic
      status and place of residence. Few studies have taken dietary factors into
      account. Recent studies involving Chinese, Malays and Asian Indians living in
      Singapore suggest that neither dietary nor genetic factors, taken in isolation,
      sufficiently explain ethnic differences in serum lipid profiles. Several genetic
      variants in key candidate genes (apolipoprotein E, APOE, cholesteryl ester
      transfer protein, CETP and hepatic lipase, LIPC) have recently been found to
      modulate the association between dietary factors and serum lipid concentrations
      in these ethnic groups and in other populations. SUMMARY: To fully evaluate the
      differences in CHD risk between ethnic groups, environmental exposures, including
      dietary factors need to be carefully evaluated, and gene-environment interactions
      that may give rise to these differences need to be taken into account. These are
      critical steps in the development of targeted strategies to contain the epidemic
      of coronary heart disease in Asia. An understanding of the basis of these
      differences may also provide insights into the pathogenesis of disease that one
      cannot get through the examination of more homogenous populations.

PMID- 15166803
TI  - The multi-dimensional regulation of gene expression by fatty acids:
      polyunsaturated fats as nutrient sensors.
AB  - PURPOSE OF REVIEW: A diet that provides 2-5% of energy as highly unsaturated 20-
      and 22-carbon omega-6 or omega-3 fatty acids is associated with an inhibition of
      hepatic lipogenesis, a stimulation of hepatic fatty acid oxidation, and
      consequently a lowering of blood triglyceride levels. The purpose of this review
      is to demonstrate that highly unsaturated fatty acids regulate lipid metabolism
      by modulating protein expression at many levels including gene transcription,
      messenger RNA processing, mRNA decay, and post-translational protein
      modifications. Although the intracellular signaling mechanisms employed by highly
      unsaturated fatty acids are unknown, this review presents a summary of the
      emerging knowledge regarding highly unsaturated fatty acids as kinase cascade
      activators. RECENT FINDINGS: Highly unsaturated fatty acids suppress lipogenic
      gene transcription by reducing the DNA binding activity of several transcription
      factors, notably sterol regulatory-element binding protein 1 and nuclear factor
      Y. Highly unsaturated fatty acids inhibit the proteolytic release of sterol
      regulatory-element binding protein 1 from its membrane-anchored precursor through
      a ceramide-dependent signal, and impart a post-translational modification to
      nuclear factor Y. Highly unsaturated fatty acids accelerate sterol regulatory
      element binding protein 1 mRNA decay and may function as antagonistic ligands for
      liver receptor X, thereby interfering with the liver receptor X stimulation of
      sterol regulatory-element binding protein 1 gene transcription. Highly
      unsaturated fatty acid activation of peroxisome proliferator-activated receptor
      alpha combined with their displacement of the oxysterol from liver receptor X may
      'trap' liver receptor X as transcriptionally inactive peroxisome proliferator
      activated receptor alpha/liver receptor X heterodimer. The gene expression
      consequences of liver receptor X 'trapping' may explain how dietary highly
      unsaturated fatty acids lead to a repartitioning of fatty acids away from storage
      and towards oxidation. SUMMARY: The liver appears to use the highly unsaturated
      fatty acid status as a nutrient sensor to determine whether fatty acids are to be
      stored or oxidized. In this way highly unsaturated fatty acids may function as
      nutritional factors that reduce the risk of developing hepatic lipotoxicity and
      insulin resistance.

PMID- 15166804
TI  - Associations of low density lipoprotein particle composition with atherogenicity.
AB  - PURPOSE OF REVIEW: A growing body of data suggests that in addition to LDL
      cholesterol concentrations, compositional properties of LDL, including size and
      fatty acid composition, are important in determining the relative degree of
      atherogenicity. This review examines current research in this field to evaluate
      which properties of LDL may most directly influence the risk of coronary heart
      disease. RECENT FINDINGS: The presence of small dense LDL has been correlated
      with an increased risk of coronary heart disease, but this has not been shown to
      be fully independent of related factors such as elevated plasma triacylglycerol
      concentrations. An increased susceptibility of small dense LDL to in-vitro
      oxidation has also been demonstrated, but its importance to coronary heart
      disease risk has not been established. Other studies have found that the presence
      of enlarged LDL, modified (oleate enriched) fatty acyl composition of LDL, and
      higher numbers of LDL particles in plasma also are endpoints associated with an
      increased risk of coronary heart disease. SUMMARY: LDL size may indicate a
      metabolic condition associated with increased CHD risk as opposed to the direct
      promotion of atherosclerosis by specific particle types of LDL. In most claims of
      detrimental effects of small dense LDL, neither LDL particle concentrations nor
      the fatty acid composition of the particles were established, both factors being
      important in contributing to the atherogenic potential of LDL. The predisposition
      to premature coronary heart disease cannot currently be objectively assigned to
      any one type of LDL particle.

PMID- 15166805
TI  - Antiarrhythmic effects of n-3 fatty acids: evidence from human studies.
AB  - PURPOSE OF REVIEW: N-3 fatty acids from fish reduce cardiovascular mortality
      including sudden cardiac death. In this paper, the authors discuss the results of
      human studies with regard to the hypothesis that n-3 fatty acids reduce the risk
      of fatal coronary heart disease through antiarrhythmic effects. RECENT FINDINGS:
      Results from two recent clinical trials do not support a protective effect of n-3
      fatty acids. In light of the earlier published bulk of evidence that n-3 fatty
      acids reduce cardiovascular mortality and sudden cardiac death, it is hard to
      explain these findings. Two recent observational studies confirmed that intake of
      n-3 fatty acids from fish is associated with less cardiovascular disease in the
      general population. They indicated that the protective effect of a fish meal may
      depend on the n-3 fatty acid content or preparation method and suggested a
      protective effect on arrhythmia rather than on atherosclerosis. Intervention
      studies on electrophysiological predictors of arrhythmia do not clearly confirm a
      beneficial effect of n-3 fatty acids. However, most of these studies were small
      or performed in healthy populations. SUMMARY: The available evidence still
      suggests that n-3 fatty acids may prevent fatal cardiac arrhythmia, but more
      conclusive studies are urgently needed.

PMID- 15166806
TI  - Weight loss, diet composition and cardiovascular risk.
AB  - PURPOSE OF REVIEW: Low-fat high-carbohydrate diets for weight loss have been
      challenged by alternative dietary approaches such as low-carbohydrate, high
      protein or low glycaemic index. This review summarizes recent evidence on short
      term metabolic effects and long-term adherence. RECENT FINDINGS: Very low
      carbohydrate freely fed diets containing less than 60 g carbohydrate per day
      appear more effective at inducing weight loss over 6 months than low-fat
      kilojoule-controlled diets although long-term compliance to both are equally
      poor. The LDL-cholesterol level did not increase in most studies and triglyceride
      levels fell dramatically in all studies, although none of the studies measured
      lipids in energy balance. Direct comparisons of the long-term efficacy and safety
      of low-fat and low-carbohydrate ad libitum diets are needed. High-protein diets
      with moderate levels of both fat and carbohydrate and diets low in glycaemic load
      are emerging dietary strategies, with medium-term benefits having been
      demonstrated in individuals with insulin resistance. Diets low in glycaemic index
      require larger studies to establish their efficacy for weight loss and
      cardiovascular disease risk reduction. SUMMARY: A variety of dietary approaches
      to achieve weight loss are consistent with metabolic improvements in
      cardiovascular risk in the short term. Long-term efficacy may depend on the
      intensity of education and frequency of follow-up more than the dietary
      composition per se.

PMID- 15166807
TI  - Phytosterols and cholesterol metabolism.
AB  - PURPOSE OF REVIEW: Phytosterols are plant sterols structurally similar to
      cholesterol that act in the intestine to lower cholesterol absorption. Because
      they have very low systemic absorption and are already present in healthy diets,
      increasing the intake of phytosterols may be a practical way to reduce coronary
      heart disease with minimum risk. RECENT FINDINGS: Phytosterols displace
      cholesterol from intestinal micelles, reducing the pool of absorbable
      cholesterol, but they are also rapidly taken up by enterocytes and increase
      expression of the adenosine triphosphate-binding cassette A1 sterol transporter.
      Phytosterol esters dissolved in food fat reduce LDL-cholesterol by 10% at a
      maximum effective dose of 2 g/day. However, this work probably understates the
      true effectiveness of phytosterols because it does not account for those
      naturally present in baseline diets. Single meal studies show that phytosterols
      in intact foods are bioactive at doses as low as 150 mg. The potential
      effectiveness of phytosterols has been improved in several ways. Individuals most
      likely to respond have been identified as having high cholesterol absorption and
      low cholesterol biosynthesis. Phytosterols can be emulsified with lecithin and
      delivered in non-fat or low-fat foods and beverages, and the amount of fat in fat
      based preparations can be reduced substantially with the retention of
      bioactivity. SUMMARY: Phytosterols effectively reduce LDL-cholesterol when given
      as supplements, and the smaller amounts in natural foods also appear to be
      important. Future work will focus on the better delivery of phytosterols in
      natural foods and supplements and on further defining the mechanisms of action.

PMID- 15166808
TI  - Modulation of immune and inflammatory responses by dietary lipids.
AB  - PURPOSE OF REVIEW: There continues to be considerable interest in the modulating
      effect of dietary lipids on immune and inflammatory responses. Although
      controversy still exists in research in this area, new concepts and approaches
      have emerged providing useful suggestions. Analysis of the recent findings will
      help in understanding certain paradoxical findings as well as introducing new
      strategies to guide future studies. RECENT FINDINGS: The tissue polyunsaturated
      fatty acid composition was found to be correlated with changes in certain indices
      of immune function in individuals consuming habitual diets. It seems that
      individuals or animals with disordered immune systems are more reactive to
      polyunsaturated fatty acid supplementation, and genetic variation is also a
      determinant. N-3 polyunsaturated fatty acids were shown to reduce both resistance
      to bacterial infection and host survival. The studies on other non-classic fatty
      acids also demonstrated interesting findings. A proposed immuno-enhancing effect
      of conjugated linoleic acid has not been confirmed by studies and even an adverse
      effect has been implied. Trans fatty acids have been shown to increase the
      production of inflammatory cytokines, which may contribute to their pro
      atherogenic property. SUMMARY: Current data suggest that the intake of
      polyunsaturated fatty acids, particularly n-3 polyunsaturated fatty acids, can
      modulate immune and inflammatory responses, although a discrepancy is still
      present. Some recent studies have provided useful information explaining possible
      underlying reasons. Factors such as genetic variation, health status, disease,
      immune response stage, stimulation type, and possibly age, all contribute to the
      responsiveness to polyunsaturated fatty acid supplementation in terms of immune
      function.

PMID- 15166809
TI  - Folate and homocysteine interrelationships including genetics of the relevant
      enzymes.
AB  - PURPOSE OF REVIEW: Inadequate folate status has been linked to risk of a wide
      range of adverse health conditions throughout life, from birth defects and
      complications of pregnancy to cardiovascular disease, cancer and cognitive
      dysfunction in the elderly. In many instances these risks are manifested through
      elevated plasma homocysteine. This review focuses on current research into the
      contribution of genetic variability to folate status and disease predisposition.
      RECENT FINDINGS: Some dozen potentially important polymorphisms in folate-related
      genes have been examined for disease associations or for their role in
      determining the level of plasma homocysteine. In most instances, the effects are
      either modest, not significant, or undetectable. However, the mechanism by which
      the 677C-->T variant of methylenetetrahydrofolate reductase determines
      homocysteine status has become clearer with the elucidation of a critical role
      for riboflavin in modulating the plasma homocysteine of TT homozygotes. Moreover,
      several new metaanalyses have confirmed an association of this variant with
      vascular disease, probably through low folate status and elevated plasma
      homocysteine. SUMMARY: There are enormous difficulties in attempting to assess
      the contribution of minor genetic variability to nutrient status, against major
      background differences due to ethnicity, age, gender, lifestyle, dietary habits
      and disease status. Nevertheless, this is an important goal in the future
      management of chronic multifactorial disease. The present research into the
      genetic components of folate and homocysteine variability is paving the way
      towards an eventual capacity to ensure optimal folate status in every individual
      and, consequently, to reduce their risk of developing such diseases.

PMID- 15166811
TI  - Bibliography. Current world literature. Nutrition and metabolism.

PMID- 15166812
TI  - Nutrition and metabolism.

PMID- 15166810
TI  - Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV
      lipodystrophy: a model of 'systemic steatosis'.
AB  - PURPOSE OF REVIEW: This review addresses a syndrome of dyslipidemia and
      lipodystrophy that has emerged in HIV-infected patients receiving highly active
      antiretroviral therapy (HAART). The term 'HIV/HAART associated dyslipidemic
      lipodystrophy (HADL)' describes this syndrome. Although HAART increases patient
      survival rates, their increased longevity and dyslipidemias place them at risk
      for cardiovascular disease. Identification of rationally based therapies requires
      an understanding of the mechanistic basis of HADL. RECENT FINDINGS: A case
      definition for HIV lipodystrophy, based on age, gender, duration of HIV disease,
      serum HDL cholesterol and anthropometry, provides high diagnostic sensitivity and
      specificity. The dyslipidemias, mainly hypercholesterolemia, hypertriglyceridemia
      and low-plasma HDL cholesterol, among HIV-infected patients in the pre- and post
      HAART eras are summarized. Clinical studies of HADL patients show increased
      lipolysis, which increases free fatty acid transfer to liver for incorporation
      into lipoprotein triglycerides that are secreted, and to skeletal muscle where
      they impair normal insulin signaling. A model of HADL that includes preferential
      lipolysis in femoral-gluteal fat depots is presented. Relevant therapies include
      those that inhibit lipolysis (niacin) or increase hepatic fatty acid oxidation
      (fibrates). SUMMARY: HADL is one of several disorders characterized by
      dyslipidemia, insulin resistance, and lipodystrophy. The relative acuteness of
      HADL should facilitate identification of the sequence of metabolic changes that
      gives rise to the syndrome. Current evidence suggests that deranged energy
      storage in femoral-gluteal and other peripheral sites is important; the molecular
      details for the derangement are unknown but are under scrutiny by many
      investigators.

PMID- 15166813
TI  - High-density lipoprotein cholesterol levels and cholesterol efflux: a missing
      link?

PMID- 15166814
TI  - Lipid metabolism.

PMID- 15166815
TI  - The metabolic syndrome, inflammation and cardiovascular disease in type 2
      diabetes.

PMID- 15166816
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 15166817
TI  - Therapy and clinical trials.

PMID- 15166818
TI  - Pneumococcal vaccines: do they prevent infection and how?
AB  - PURPOSE OF REVIEW: The purpose of this review is to update and summarize
      information concerning the epidemiology of infections due to Streptococcus
      pneumoniae and the early results of effectiveness studies of the heptavalent
      pneumococcal conjugate vaccine. This vaccine was licensed in the US in 2000, and
      has been used increasingly since that time. RECENT FINDINGS: Several studies have
      documented a dramatic decline in the rate of invasive infections due to S.
      pneumoniae in children under 5 years of age. There has been a simultaneous
      decrease in serious infections in persons over 20 years of age, presumably
      because of a decrease in transmission of S. pneumoniae to unvaccinated
      individuals. Three different studies have shown a modest reduction in the overall
      number of cases of acute otitis media in children who have received the vaccine.
      Although the overall number of cases has decreased there has been an increase in
      the number of cases of acute otitis media caused by serotypes of S. pneumoniae
      not contained in the vaccine. Worldwide, many studies have appeared that examine
      the prevalence of different pneumococcal serotypes/serogroups as a cause of
      invasive and respiratory disease, to assess the likelihood that the vaccine will
      be effective in particular geographic areas. SUMMARY: Use of the heptavalent
      pneumococcal conjugate vaccine has led to a major decline in the prevalence of
      invasive pneumococcal disease (bacteremia, meningitis) and a more modest decrease
      in respiratory tract infections (acute otitis media, pneumonia). Continued
      surveillance is essential to document future trends in the occurrence of
      pneumococcal infections and the enduring protectiveness of the heptavalent
      pneumococcal conjugate vaccine.

PMID- 15166819
TI  - How do viral infections predispose patients to bacterial infections?
AB  - PURPOSE OF REVIEW: Bacterial sepsis is a leading cause of death in the United
      States, accounting for over 200,000 fatalities annually. Approximately half of
      bacterial sepsis cases occur following acute respiratory infections, and the
      lungs are the most common organs to fail. Notably, outbreaks of respiratory viral
      infections are associated with an increased incidence or severity of bacterial co
      infections, with normally innocuous infections often becoming fatal.
      Understanding the 'lethal synergism' associated with concomitant infections may
      point the way toward improved anti-sepsis treatments. RECENT FINDINGS: Murine
      models of viral and bacterial co-infection mimic the lethal synergism observed in
      humans and reveal at least two mechanisms of interaction. First, bacterial
      infiltration is heightened during acute viral infection. Secondly, the nature of
      responding cell populations is dramatically altered during concomitant
      infections. Although natural killer cells and macrophages are predominant cell
      populations responding to bacterial infection in a naive host, there is also a
      large T cell component that is activated upon viral infection. Inflammatory
      cytokines produced by these cells contribute to lethal immunopathology, and
      therapeutic strategies need to target the initial causative microbes as well as
      subsequent inflammatory responses. Current therapies directed only at the host
      immune response have not been overly successful, owing largely to difficulties in
      reversing the severe immunopathology associated with sepsis. SUMMARY: Respiratory
      viral infections may facilitate secondary bacterial infections and increase host
      immunopathology through the overproduction of inflammatory cytokines. Preventive
      measures, including vaccination and aggressive antimicrobial therapy early in the
      course of infection, may significantly reduce the morbidity and mortality of
      sepsis.

PMID- 15166820
TI  - Immune responses in hepatitis C: is virus or host the problem?
AB  - PURPOSE OF REVIEW: Hepatitis C virus is an RNA virus that usually establishes
      persistent infection in its host. As an important cause of cirrhosis and
      hepatocellular carcinoma worldwide, hepatitis C is a growing public health
      concern. Despite recent advances in therapy, most people infected with the virus
      can expect lifelong infection. In the minority of those exposed and who
      spontaneously clear virus, a robust hepatitis C virus-specific T cell response of
      T helper 1 type correlates with resolution. The longevity of this response in the
      recovered state and the potential for hepatitis C virus-specific T cells to
      protect against future infection are critical parameters for vaccine design.
      RECENT FINDINGS: The literature of the past year dissected components of
      protective immunity to hepatitis C and emphasized the importance of the CD4
      helper response in both the expansion and maintenance of hepatitis C virus
      specific CD8(+) T cells. Other important studies examined how the virus interacts
      with immune cells to subvert both innate and adaptive immune responses in acute
      and chronic infection. SUMMARY: Defining the essential components of protective
      immunity against a highly mutable virus like hepatitis C underpins successful
      vaccine design. By understanding viral and host factors which influence hepatitis
      C virus-specific T cell maintenance and function, we are better equipped to
      devise immunomodulatory therapies and vaccines which induce robust and lasting
      immunity.

PMID- 15166821
TI  - The host response to herpes simplex virus infection.
AB  - PURPOSE OF REVIEW: Infection with herpes simplex virus remains a significant
      cause of disease. The host immune system plays an important role in containing
      viral replication, and there has been considerable progress in defining which
      components of immunity are key to the resolution of infection. Nevertheless,
      effective immunoprophylaxis or immunotherapy has not yet been achieved. RECENT
      FINDINGS: Recent work has focused on understanding the early events leading to
      the herpes simplex virus-specific immune response, in particular on the role of
      antigen-presenting dendritic cells. Herpes simplex virus has evolved a number of
      ways of interfering with antigen presentation by dendritic cells, thus presumably
      impeding or delaying the host immune response. Nevertheless, herpes simplex virus
      triggers strong cellular and humoral immunity. The ability of dendritic cells to
      take up dead or dying infected cells and cross-present them to cognate T cells
      may be the key to resolving this apparent paradox. Interaction between dendritic
      cell subsets, and particularly the virus-induced release of type I interferons
      may be essential to drive efficient antigen cross-presentation and subsequent T
      cell activation. SUMMARY: A greater understanding of the importance of dendritic
      cells in driving viral immunity, and of the ligands that activate these cells and
      the cytokines they secrete, has provided novel vaccination strategies. The
      delivery of immunomodulatory genes together with viral antigens, for example by
      DNA vaccination, may harness the full potential of dendritic cells, and achieve
      the goal of effective immunological control of herpes simplex virus.

PMID- 15166822
TI  - Activated protein C in sepsis: emerging insights regarding its mechanism of
      action and clinical effectiveness.
AB  - PURPOSE OF REVIEW: Dysregulation of endogenous coagulant and anticoagulant
      systems is now believed to play an important role in the pathogenesis of sepsis
      and septic shock. Reductions in host activated protein C levels and resultant
      microvascular thrombosis provided a basis for the use of recombinant human
      activated protein C in sepsis. Although controversial, the findings from an
      initial phase III trial testing this agent resulted in its approval for use in
      patients with severe sepsis and high risk of death. This review highlights
      emerging insights into the biology of protein C and activated protein C in
      sepsis, summarizes additional analysis growing out of the phase III trial testing
      recombinant human activated protein C, and assesses the cost-effectiveness that
      the clinical use of the agent has had thus far. RECENT FINDINGS: Binding of
      activated protein C to the endothelial cell protein C receptor is recognized to
      result in a growing number of actions including increased activity of activated
      protein C itself and inhibition of both nuclear factor-kappaB, a central
      regulator in the host inflammatory response, and apoptosis. Additional analysis
      of the original phase III trial testing recombinant human activated protein C
      appears to emphasize one of the US Food and Drug Administration's original
      concerns regarding an association between severity of sepsis and this agent's
      effects. Postmarketing analysis and growing experience with other anticoagulant
      agents and corticosteroids in sepsis raise questions regarding the ultimate cost
      effectiveness of activated protein C. SUMMARY: The protein C pathway is important
      both to coagulant and inflammatory pathways during sepsis. Based on emerging
      investigations, its actions appear to be increasingly complex ones. Despite
      potentially promising results in an initial phase III trial, the role of
      recombinant human activated protein C in the treatment of septic patients must
      continue to be evaluated.

PMID- 15166823
TI  - What is the effect of prepartum antimicrobials on neonatal infection?

PMID- 15166824
TI  - Serious bacterial infections in newborn infants in developing countries.
AB  - PURPOSE OF REVIEW: The overwhelming majority of the world's annual 4 million
      neonatal deaths occur in developing countries. This review therefore briefly
      addresses the burden, aetiology, prevention and management of serious neonatal
      bacterial infections in low-income settings. RECENT FINDINGS: Bacterial infection
      is the biggest cause of neonatal admissions to hospitals, and probably the
      biggest cause of morbidity in the community, but its burden is unclear. The
      commonest serious infections involve bacteraemia, meningitis and respiratory
      infection, and case fatality rates may be as high as 45%. Key pathogens are
      Escherichia coli, Klebsiella species, Staphylococcus aureus and Streptococcus
      pyogenes. The incidence of neonatal infections with group B streptococcus is
      highly variable, as is the spectrum of antimicrobial resistance. SUMMARY: Current
      areas of research include the rectification of micronutrient deficiencies,
      neonatal skin care, appropriate breastfeeding recommendations, cleansing of the
      birth canal, and simplified methods of diagnosis of infection. Operational
      activities include the control of neonatal tetanus, the diagnosis and treatment
      of sexually transmitted infections, integrated strategies for improving
      pregnancy, childbirth and neonatal survival, community-based management of acute
      respiratory infections, and community-based management of neonatal sepsis.

PMID- 15166825
TI  - Bacterial virulence factors in neonatal sepsis: group B streptococcus.
AB  - PURPOSE OF REVIEW: Group B streptococcus is a leading cause of neonatal
      pneumonia, septicaemia and meningitis. Up to one quarter of women in labour are
      now given intravenous antibiotics to prevent early-onset disease by the organism,
      a situation that will remain constant until a successful vaccine is available.
      From a molecular understanding of the pathogenicity of group B streptococcus we
      may be able to devise novel means for controlling disease, such as identifying
      inhibitors of key metabolic pathways or regulatory networks. This review
      summarizes our post-genomic knowledge of the regulation, metabolism and virulence
      of group B streptococcus. RECENT FINDINGS: Although advances have been made in
      the understanding of classic group B streptococcus virulence traits, such as
      capsular polysaccharide, beta-haemolysin, C5a peptidase, adhesins and immunogenic
      surface proteins, the major recent contribution to group B streptococcus
      pathogenesis has been the whole genome sequencing of three group B streptococcus
      strains, representing serotypes Ia, III and V. From these genomes, we not only
      see where the classic virulence genes map, but we can also gain insights into the
      metabolism and regulation of the organism and how these affect its virulence.
      SUMMARY: Knowledge of virulence factors and the organism's metabolism and gene
      regulation offers opportunities to find novel means of preventing group B
      streptococcus infection in babies.

PMID- 15166827
TI  - Coagulase-negative staphylococcal disease: emerging therapies for the neonatal
      and pediatric patient.
AB  - PURPOSE OF REVIEW: Due to the high frequency, significant clinical impact, and
      cost of coagulase-negative staphylococcal infections, a great deal of effort
      continues in the investigation of the epidemiology, prevention, and treatment of
      coagulase-negative staphylococcal infection in the neonate and infant. RECENT
      FINDINGS: Pediatric oncology and burn patients appear to be high-risk groups for
      coagulase-negative staphylococcal infections. Coagulase-negative staphylococcus
      appears to be the major pathogen world-wide, and associated with significant
      morbidity and mortality in neonatal intensive care units, in pediatric intensive
      care units, and following ophthalmologic surgery. A screened human polyclonal
      antibody and a humanized chimeric monoclonal antibody are both under
      investigation (in phase II-III clinical trials) for prevention of coagulase
      negative staphylococcal infections in high-risk neonates. Resistance of coagulase
      negative staphylococcus to antibiotics appears to be increasing. Should neonates
      with sepsis and central catheters have their catheters removed immediately or
      only when the infection is persistent? Arbekacin and linezolid are two new
      antibiotics that appear to be effective in the treatment of coagulase-negative
      staphylococcal infections, but their precise role has not yet been identified.
      SUMMARY: This article summarizes the significant clinical reports about coagulase
      negative staphylococcal infections since December 2002.

PMID- 15166828
TI  - Neonatal herpes simplex virus infection.
AB  - PURPOSE OF REVIEW: In spite of the availability of antiviral therapy for the
      treatment of neonatal herpes simplex virus infections, the outcome remains poor,
      particularly for babies with disseminated multi-organ infection or central
      nervous system disease. This review considers recent advances that impact on
      disease management. RECENT FINDINGS: Two areas of investigation have impacted on
      our understanding of neonatal herpes simplex virus infection. First, the
      transmission of infection from mother to baby has been clarified by extensive
      epidemiological investigations of genital herpes in pregnant women at term. Risk
      factors for neonatal herpes simplex virus disease include first-episode maternal
      infection in the third trimester, invasive monitoring, delivery before 38 weeks,
      and maternal age of less than 21 years. Regarding the management of neonatal
      herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg
      every 8 h) for 21 days significantly reduces mortality for babies with either
      encephalitis or disseminated disease. SUMMARY: Recent findings from
      epidemiological studies have identified women at risk of delivering a child who
      develops neonatal herpes simplex virus infection, and suggest methods to decrease
      maternal-fetal transmission. If infection is identified in the pregnant woman,
      cesarean delivery decreases the frequency of neonatal disease. With neonatal
      disease, acyclovir should be administered promptly at higher dosages and for
      longer periods than previously reported.

PMID- 15166826
TI  - Late-onset infection and the role of antibiotic prescribing policies.
AB  - PURPOSE OF REVIEW: Late-onset infection is a significant cause of morbidity and
      mortality in low-birth-weight and premature infants. Empirical antibiotic
      treatment is used as infants can deteriorate rapidly without treatment. Current
      data on the epidemiology of late-onset infection, the types of antibiotics used,
      duration of antibiotic use, and antibiotic prescribing policies are reviewed.
      RECENT FINDINGS: Epidemiological data on late-onset sepsis is dominated by
      information concerning developed countries; large prospective data collections
      have been set up in many such countries. Recent data indicate that late-onset
      sepsis occurs in one-fifth of very-low-birth-weight infants. There are increasing
      concerns regarding antibiotic resistance. Antibiotic regimens that do not include
      third-generation cephalosporins produce less resistance. Strategies of antibiotic
      rotation have not been documented as producing a marked effect on the development
      of resistant micro-organisms, but there is a lack of randomized trials.
      Recommendations for preventing the spread of vancomycin-resistant enterococci,
      produced by the Hospital Infection Control Practices Advisory Committee, have
      been shown to be effective in a number of situations. Recent reports have
      documented the success of multidisciplinary, systems-orientated approaches for
      reducing neonatal nosocomial infection. SUMMARY: Antibiotic prescribing policies
      have an important role to play in the treatment of late-onset neonatal infection.
      There is enough evidence to state that narrow-spectrum antibiotics should be used
      wherever possible and that potent broad-spectrum antibiotics should be kept in
      reserve. Ongoing prospective surveillance of infection rates, micro-organisms,
      resistance and antibiotic use is essential.

PMID- 15166829
TI  - Prevention of mother-to-child transmission of HIV infection.
AB  - PURPOSE OF REVIEW: Mother-to-child transmission of HIV infection is the primary
      cause of paediatric HIV infections worldwide. Although clinical trials show that
      antiretroviral therapy, elective caesarean section and formula feeding can
      significantly reduce the peripartum or postpartum risk of transmission, their
      application on a population basis is challenging. There is a need for
      alternative, easier and more effective interventions for population-based
      programmes. RECENT FINDINGS: This review addresses recent advances in our
      understanding of mother-to-child transmission risk factors, including maternal
      viral load (in plasma, genital tract and breast milk) and gender, and
      determinants and rates of postnatal transmission. New information on prophylactic
      antiretroviral therapy includes results from randomized trials in Africa and
      Thailand, in addition to new information on implementation of prevention of
      mother-to-child transmission programmes in nontrial settings, in both developed
      and developing countries. Two important issues relating to use of antiretroviral
      prophylaxis are discussed: safety and toxicity, including new findings on
      haemopoiesis, prematurity and mitochondrial abnormalities in antiretroviral
      therapy-exposed infants and children, and resistance. Recent trends and
      controversies relating to mode of delivery in HIV-infected pregnant women are
      outlined. Regarding infant feeding, preliminary results on use of mono
      antiretroviral therapy to prevent postnatal transmission in breastfeeding HIV
      exposed infants are discussed. SUMMARY: In resource-rich settings, virtual
      elimination of mother-to-child transmission is theoretically possible. Even in
      these settings, however, a substantial number of infected women are not being
      identified early enough for optimum application of prevention of mother-to-child
      transmission interventions. In developing country settings, focus is being
      directed towards scaling-up prevention programmes now that trials have
      established a variety of effective antiretroviral prophylactic approaches.

PMID- 15166834
TI  - Vasopressor agents: old and new components.
AB  - PURPOSE OF REVIEW: In settings of cardiac arrest, reestablishing vital organ
      perfusion plays an important role in initial CPR. As a pharmacologic
      intervention, vasopressor agents aim to improve aortic diastolic pressure and,
      consequently, coronary and cerebral perfusion pressures. RECENT FINDINGS:
      Historically, adrenergic agonists such as epinephrine have been suggested for
      routine use in CPR. However, epinephrine's efficacy is controversial because of
      its unfavorable inotropic and chronotropic action. This has prompted research
      into the use of alternative pressor agents with more promising hemodynamic
      features; these include selective alpha 2-adrenergic agonists and other
      nonadrenergic vasoconstrictors such as vasopressin. SUMMARY: In this article, the
      main traditional and novel adrenergic and nonadrenergic vasopressor drugs are
      reviewed.

PMID- 15166830
TI  - Fungal infection in the very low birthweight infant.
AB  - PURPOSE OF REVIEW: Fungal infections are prevalent in very low birthweight (<1500
      g) infants and are associated with significant morbidity and mortality. A better
      understanding of the adherence factors, molecular diagnostics and risk factors
      for invasive fungal infection are important in treatment and prevention. RECENT
      FINDINGS: Animal studies have demonstrated that Candida readily adheres to apical
      microvilli and the junctions between enterocytes. Although antibiotics facilitate
      colonization, dissemination occurs with immunosuppression. The INT1 gene is
      associated with enhanced colonization and dissemination in these animal models.
      Dissemination is probably caused by yeast cell adherence and invasion, whereas
      tissue injury may be related to filamentous formation. Polymerase chain reaction
      techniques have demonstrated promise in neonatal patients and may not only detect
      bloodstream infection, but fungal infection at other sites. At the time of fungal
      sepsis, less than 28 weeks' gestation, thrombocytopenia, and previous exposure to
      broad-spectrum antibiotics continue to be risk factors for infection. Empiric
      therapy is still being defined and investigated. Fluconazole prophylaxis should
      be strongly considered in the most immature infants. SUMMARY: Preventative
      strategies against fungal colonization and infection are critical in high-risk
      very low birthweight infants. Also promising is the ability of molecular
      diagnostics to detect infection earlier, allowing for prompt treatment, including
      central venous catheter removal. Identifying the highest risk very low
      birthweight infants for prophylaxis and empiric therapy may lead to better
      outcomes. Multicenter clinical trials of fluconazole prophylaxis to confirm its
      safety and efficacy, and of empiric treatment to test safety and outcomes are
      urgently needed.

PMID- 15166835
TI  - New devices for generating blood flow during cardiopulmonary resuscitation.

PMID- 15166836
TI  - Combination of active compression decompression cardiopulmonary resuscitation and
      the inspiratory impedance threshold device: state of the art.
AB  - PURPOSE OF REVIEW: Over the past decade, the combination of active compression
      decompression (ACD) cardiopulmonary resuscitation (CPR) and an impedance
      threshold device (ITD) has been shown to significantly increase vital organ
      perfusion pressures and survival rates in animals and humans. The purpose of this
      review article is to summarize the recent advances with this new technology.
      RECENT FINDINGS: Building upon animal studies that demonstrated the benefit of
      the ITD used with either ACD CPR or standard CPR (S-CPR), four prospective,
      randomized clinical trials with ACD/ITD CPR have been recently completed. One
      blinded, out-of-hospital cardiac arrest trial (n = 21 patients) demonstrated that
      systemic blood pressures and coronary perfusion pressures were markedly higher
      when ACD/ITD CPR was used when compared directly with ACD CPR alone. The second
      blinded trial demonstrated that the combination of ACD/ITD CPR was effective with
      both a facemask and an endotracheal tube (n = 15 patients). A third randomized
      clinical trial (n = 210 patients) demonstrated that 24-hour survival rates for
      out-of-hospital cardiac arrest were more than 65% higher with ACD/ITD CPR than
      with S-CPR (P < 0.01). Neurologic function after cardiac arrest trended higher in
      patients with witnessed arrest who received ACD/ITD CPR than in those who
      received S-CPR(P < 0.07). In addition, when ACD/ITD CPR was applied later in the
      course of treatment, short-term survival rates were threefold higher in patients
      receiving ACD/ITD CPR (44%) than in those receiving S-CPR (14%)(P < 0.05). In
      that study, patients with the greatest chance for survival-those with witnessed
      cardiac arrest and an initial rhythm of ventricular fibrillation-had a 23% 24
      hour survival rate with S-CPR versus a 58% 24-hour survival rate with ACD/ITD CPR
      (P < 0.01). It should be noted that this trial was performed in a city where an
      earlier study found no difference in outcomes between ACD CPR alone and S-CPR.
      The fourth clinical trial was a randomized, double-blinded study of 400 patients
      with out-of-hospital cardiac arrest treated by advanced life support personnel.
      All patients received ACD CPR: half were treated with a sham ITD and the other
      half were treated with an active ITD. Twenty-four hour survival, the primary
      endpoint, was 32% in the active ITD group versus 22% in the sham group (P <
      0.05). SUMMARY: On the basis of the cumulative findings of these studies, it is
      concluded that ACD/ITD CPR provides superior vital organ blood flow and results
      in significantly higher short-term survival rates than do ACD CPR alone or S-CPR.
      Use of the ACD/ITD CPR technology optimizes perfusion of the heart and brain
      during cardiac arrest and results in the highest reported survival rates of any
      CPR device technology. Use of this technology should be encouraged while
      additional studies are under way to examine the potential long-term impact of
      this new technology.

PMID- 15166837
TI  - Waveforms for defibrillation and cardioversion: recent experimental and clinical
      studies.
AB  - PURPOSE OF REVIEW: The advent of biphasic waveforms for external defibrillation
      has generated extensive experimental and clinical investigation. At the same
      time, it has led to the development and clinical use of biphasic waveforms of
      several different designs. Finally, other types of waveforms, primarily
      triphasic, have entered experimental evaluation. RECENT FINDINGS: There is
      virtually universal agreement that biphasic waveforms, regardless of design, have
      greater efficacy in defibrillation of ventricular fibrillation and in
      cardioversion of atrial fibrillation when compared with monophasic waveforms. It
      remains unresolved, however, whether any specific biphasic waveform has greater
      clinical superiority than others. Likewise, it remains to be demonstrated whether
      any biphasic waveform is less injurious to myocardial function than another and
      whether injury, if it is incurred, is secondary to peak delivered current or to
      delivered energy. Biphasic truncated exponential waveforms are used by most
      manufacturers, whereas a rectilinear biphasic waveform and a pulsed waveform also
      are being used clinically. SUMMARY: Biphasic waveforms have supplanted monophasic
      waveforms for defibrillation and cardioversion. They include biphasic truncated
      exponential, rectilinear, and pulsed biphasic versions. At this time, there is no
      certain evidence of clinical superiority of one waveform over another in terms of
      either efficacy or myocardial injury.

PMID- 15166838
TI  - Postresuscitation disease after cardiac arrest: a sepsis-like syndrome?
AB  - PURPOSE OF REVIEW: Despite advances in cardiac arrest resuscitation, neurologic
      impairments and other organ dysfunctions cause considerable mortality and
      morbidity after restoration of spontaneous cardiac activity. The mechanisms
      underlying this postresuscitation disease probably involve a whole-body ischemia
      and reperfusion syndrome that triggers a systemic inflammatory response. RECENT
      FINDINGS: Postresuscitation disease is characterized by high levels of
      circulating cytokines and adhesion molecules, the presence of plasma endotoxin,
      and dysregulated leukocyte production of cytokines: a profile similar to that
      seen in severe sepsis. Transient myocardial dysfunction can occur after
      resuscitation, mainly as a result of myocardial stunning. However, early
      successful angioplasty is independently associated with better outcomes after
      cardiac arrest associated with myocardial infarction. Coagulation abnormalities
      occur consistently after successful resuscitation, and their severity is
      associated with mortality. For example, plasma protein C and S activities after
      successful resuscitation are lower in nonsurvivors than in survivors. Low
      baseline cortisol levels may be associated with an increased risk of fatal early
      refractory shock after cardiac arrest, suggesting adrenal dysfunction in these
      patients. SUMMARY: Postresuscitation abnormalities after cardiac arrest mimic the
      immunologic and coagulation disorders observed in severe sepsis. This suggests
      that therapeutic approaches used recently with success in severe sepsis should be
      investigated in patients successfully resuscitated after cardiac arrest.

PMID- 15166839
TI  - Brain function after resuscitation from cardiac arrest.
AB  - PURPOSE OF REVIEW: In industrial countries the incidence of cardiac arrest is
      still increasing. Almost 80% of cardiac arrest survivors remains in coma for
      varying lengths of time and full cerebral recovery is still a rare event. After
      successful cardiopulmonary resuscitation, cerebral recirculation disturbances and
      complex metabolic postreflow derangements lead to death of vulnerable neurons
      with further deterioration of cerebral outcome. This article discusses recent
      research efforts on the pathophysiology of brain injury caused by cardiac arrest
      and reviews the beneficial effect of therapeutic hypothermia on neurologic
      outcome along with the recent approach to prognosticate long-term outcome by
      electrophysiologic techniques and molecular markers of brain injury. RECENT
      FINDINGS: Recent experimental studies have brought new insights to the
      pathophysiology of secondary postischemic anoxic encephalopathy demonstrating a
      time-dependent cerebral oxidative injury, increased neuronal expression, and
      activation of apoptosis-inducing death receptors and altered gene expression with
      long-term changes in the molecular phenotype of neurons. Recently, nuclear MR
      imaging and MR spectroscopic studies assessing cerebral circulatory recovery
      demonstrated the precise time course of cerebral reperfusion after cardiac
      arrest. Therapeutic hypothermia has been shown to improve brain function after
      resuscitation from cardiac arrest and has been introduced recently as beneficial
      therapy in ventricular fibrillation cardiac arrest. SUMMARY: Electrophysiologic
      techniques and molecular markers of brain injury allow the accurate assessment
      and prognostication of long-term outcome in cardiac arrest survivors. In
      particular, somatosensory evoked potentials have been identified as the method
      with the highest prognostic reliability. A recent systematic review of 18 studies
      analyzed the predictive ability of somatosensory evoked potentials performed
      early after onset of coma and found that absence of cortical somatosensory evoked
      potentials identify patients not returning from anoxic coma with a specificity of
      100%.

PMID- 15166840
TI  - Quality of life and prognosis among survivors of out-of-hospital cardiac arrest.
AB  - PURPOSE OF REVIEW: We reviewed the topic of quality of life and prognosis of out
      of-hospital cardiac arrest survivors, focusing on more recent developments.
      RECENT FINDINGS: In 2003 to 2004, published experiences from Canada, the United
      States, and Europe indicate that the quality of life among out-of-hospital
      cardiac arrest survivors is acceptable and that prognosis may be improving over
      time. However, a minority of survivors has substantial neurologic impairment that
      adversely affects the quality of life and prognosis. Recent investigations
      indicate that bystander CPR, early defibrillation by nontraditional first
      responders, and active induction of hypothermia offer potential means to improve
      functional outcomes that may translate into better quality of life and prognosis.
      Acute treatment of the underlying etiology and effective secondary prevention
      also can benefit the out-of-hospital cardiac arrest survivor, although only a
      portion who could benefit appear to receive these therapies. SUMMARY: The optimal
      strategy for improving long-term outcomes requires a multifaceted, integrative
      approach that begins with prehospital care and extends to secondary prevention.

PMID- 15166841
TI  - Bibliography. Current world literature. Cardiopulmonary resuscitation.

PMID- 15166842
TI  - Epidemiology of acute lung injury and acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress
      syndrome (ARDS) are diseases with a significant influence in the public health. A
      better knowledge of their epidemiology could help to improve the outcome of these
      diseases. RECENT FINDINGS: Although the clinical criteria of the American
      European Consensus Conference definitions for ALI and ARDS are simple, there is a
      risk of misclassification due to a poor reliability. Except for new emerging
      infectious diseases, such as severe acute respiratory syndrome, the etiology of
      ALI/ARDS has remained the same for several years. The only recent innovation is
      the hypothesis that pulmonary ARDS and extrapulmonary ARDS could be different
      clinical entities. In recent years, there has been a special interest in the
      study of genetic predisposition to development ALI/ARDS. Recent studies have
      estimated the incidence of these diseases to be between 15 and 34 cases per
      100,000 inhabitants per year. This wide range could stem from differences in the
      methodology used to calculate the incidence or could be a true variation due to
      regional differences. Mortality rate of ALI/ARDS have remained steady for several
      years. Respiratory failure is the cause of the death in less than 20% of the
      patients. SUMMARY: The epidemiology of ALI and ARDS has some issues to improve,
      such as the accuracy of the clinical criteria of ALI/ARDS. Future research must
      to include study of genetic polymorphisms of the mediators involve in the
      development of ALI/ARDS. Studies to define better the population at risk are
      necessary to estimate better their true incidence.

PMID- 15166843
TI  - Mechanical ventilation in children with acute respiratory failure.
AB  - PURPOSE OF REVIEW: Acute respiratory failure requiring mechanical ventilation
      continues to contribute to mortality and affect long-term functional outcomes in
      patients admitted to the pediatric intensive care unit (ICU). Studies in adults
      with acute respiratory distress syndrome (ARDS) far outnumber those conducted in
      the pediatric age group, and pediatric intensivists are left with the task of
      carefully selecting and critically appraising relevant adult data and
      extrapolating results to their domain of practice. RECENT FINDINGS: The recent
      ARDSNet study reinforces the use of low tidal volumes. Administration of
      surfactant is safe, but once again its beneficial effect was not sustained in a
      randomized trial. Surfactant proteins A and D have been shown to be of prognostic
      value in cases of acute lung injury. The effect of inhaled nitric oxide (NO) in
      patients with ARDS can be enhanced by aggressive lung recruitment strategies such
      as can be achieved using high-frequency oscillatory ventilation (HFOV). A recent
      adult trial shows good response rates but no significant long-term outcome
      benefit from prone positioning in patients with ARDS. Routine scheduled
      assessments of readiness for weaning and extubation may be more important than
      specific weaning modes and weaning criteria for children. A recent meta-analysis
      suggests that prophylactic dexamethasone use may decrease postextubation stridor
      and possibly reduce the need for reintubation in selected patients. Outcome data
      in children requiring mechanical support is encouraging, especially for high-risk
      groups such as bone marrow transplant (BMT) recipients, and may guide ethically
      challenging decision-making for these patients. SUMMARY: Mechanical ventilation
      strategies aiming for optimal alveolar recruitment with the judicious use of
      positive end-expiratory pressure (PEEP) and low tidal volumes will remain the
      mainstay for managing respiratory failure in children. Dexamethasone may prevent
      postextubation stridor. Prone positioning, surfactant therapy, HFOV, and inhaled
      NO are used sporadically and need to be evaluated for their effect on mortality
      and duration of ventilation.

PMID- 15166844
TI  - Understanding and managing fluid balance in patients with acute lung injury.
AB  - PURPOSE OF REVIEW: Acute lung injury (ALI) and the acute respiratory distress
      syndrome (ARDS) affect hundreds of thousands of people each year worldwide,
      resulting in a significant healthcare burden. Over the past four decades, much
      has been discovered regarding the pathophysiology of lung injury, yet little
      progress has been made in advancing effective treatment strategies. In this
      article, we discuss the current knowledge as to fluid balance in the
      pathophysiology of ALI/ARDS and the recent innovations that have been described
      related to manipulations of hydrostatic or oncotic pressure in this condition.
      RECENT FINDINGS: Hypoproteinemia is a clear marker for ALI/ARDS and may play a
      pathophysiologic role given its independent prognostic value. Fluid balance and
      oncotic pressure alterations induced by diuretic and colloid therapy improve
      respiratory physiology and likely alter net flux of fluid across the injured
      capillary-alveolar membrane. Chest radiographs serve as a useful adjunctive tool
      in monitoring longitudinal fluid balance manipulations in ALI/ARDS. SUMMARY:
      Manipulation of Starling forces in established ALI/ARDS produces significant
      physiologic benefit and may influence outcome. Future research should focus on
      determining a mortality benefit with this readily available intervention.

PMID- 15166845
TI  - Surfactant therapy for acute lung injury/acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: Currently, three phase III surfactant replacement trials for
      acute lung injury (ALI)/acute respiratory distress syndromes (ARDS) patients are
      underway. Although the efficacy of surfactant replacement therapy will first have
      to be proved in these phase III trials, recent reports indicate some enticing
      possibilities for the future of surfactant therapy. RECENT FINDINGS: Patients
      requiring mechanical ventilation show alterations in their endogenous surfactant
      composition. Depending on the type of lung injury or the elapsed time,
      modifications to surfactant preparations could enhance the efficacy of these
      preparations. Surfactants that closely resemble natural surfactant, especially
      those containing surfactant proteins (SP-B/C) and nonphospholipids (cholesterol),
      are able to restore normal surfactant physiology. Furthermore, lipids that are
      able to withstand degradation by lipases could further enhance surfactant
      therapy. SUMMARY: If surfactant therapy fulfills the promises expected from the
      ongoing phase III trials, future surfactant preparations may even enhance therapy
      efficacy and restore the altered endogenous surfactant pool as soon as possible.

PMID- 15166846
TI  - Understanding and implementing advances in ventilator capabilities.
AB  - PURPOSE OF REVIEW: To review the changes in mechanical ventilation technology
      over the past year and identify areas that provide a benefit. RECENT FINDINGS:
      The literature demonstrates a continued effort to improve patient ventilator
      synchrony though the development of new triggering and cycling methods. These
      techniques include using new signals and using closed loop techniques to respond
      to changes in patient breathing pattern. New modes of ventilation continue to be
      introduced, often without proof of efficacy. Fortunately, clinicians have
      developed alterations to new modes that improve utility and they continue to
      study these techniques clinically to determine appropriate use. Monitoring the
      patient remains an important area of investigation, with a flurry of activity
      surrounding pressure volume curves of the respiratory system. Finally, new
      ventilators have been introduced that combine high-end performance with small
      size and weight, while providing an on-board source of air. SUMMARY: Mechanical
      ventilation is ubiquitous to intensive care. Advances in ventilator technology
      are rapid, and clinicians must keep abreast of changes in ventilator performance
      and application.

PMID- 15166847
TI  - Implementing effective ventilator practice at the bedside.
AB  - PURPOSE OF REVIEW: New data on the efficacy of low tidal volume ventilation for
      acute lung injury, noninvasive ventilation for chronic obstructive pulmonary
      disease exacerbation, weaning from mechanical ventilation, and prevention of
      ventilator-associated pneumonia provide, for perhaps the first time in
      respiratory care, compelling evidence for clinicians to change practice. However,
      experience from every other field in medicine suggests that there will be
      significant barriers to changing clinical practice at the bedside. Studies on
      implementation of effective practice in medicine shows that a multifaceted, team
      oriented approach incorporating reminders, efficient use of non-physician
      personnel, protocols, and education is required to change clinical practice.
      Limited data on current practice of mechanical ventilation suggest that it
      deviates from recommended practice. Unfortunately, there are no studies exploring
      community-based implementation of mechanical ventilation guidelines and only a
      few studies to inform clinicians as to why ventilator practice may be difficult
      to change. As the evidence base grows for effective critical care practice, so
      does the responsibility to translate practices that improve outcome from research
      journals to patients' bedsides. Strategies for doing this are presented in the
      review.

PMID- 15166848
TI  - Management of sedation in mechanically ventilated patients.
AB  - PURPOSE OF REVIEW: There are many new and exciting studies in the sedation
      literature. Recent studies of new scoring systems to monitor sedation, new
      medications, and new insights into post-intensive care unit (ICU) sequelae have
      brought about interesting ideas for achieving an adequate level of sedation of
      our patients while minimizing complications. RECENT FINDINGS: The recent
      literature focuses on monitoring the level of a patient's sedation with new
      bedside clinical scoring systems and new technology. Outcomes studies have
      highlighted problems with both inadequate sedation and excessive sedation in
      regard to patients' post-ICU psychological health. More insight into drug
      withdrawal and addiction as complications of ICU care were examined. A new
      medication for sedation in the ICU has been approved for use, but its role is not
      yet defined. SUMMARY: Many patients in the ICU receive mechanical ventilation and
      will require sedative medications. A frequently overlooked cause of agitation in
      the ventilated patient is pain, and assessing the adequacy of analgesia is an
      important part of the continuous assessment of a patient. The goal of sedation is
      to provide relief while minimizing the development of drug dependency and
      oversedation. Careful monitoring with bedside scoring systems, the appropriate
      use of medications, and a strategy of daily interruption can lead to diminished
      time on the ventilator and in the ICU.

PMID- 15166849
TI  - Paresis following mechanical ventilation.
AB  - PURPOSE OF REVIEW: To review the medical literature on neuromuscular
      abnormalities acquired in the intensive care unit (ICU), particularly after
      mechanical ventilation, focusing on the most recent advances in this field.
      RECENT FINDING: Using a simple bedside muscle strength score, significant
      clinical weakness is detected in one fourth of patients awakening in ICU after
      more than 1 week of mechanical ventilation. Weakness is associated with a longer
      time on mechanical ventilation, although the exact relationship between limb and
      respiratory neuromuscular involvement remains unclear. Muscle involvement is
      often combined with axonal involvement and can predominate or occur in isolation
      in some patients. Although prolonged severe weakness is unusual, milder
      abnormalities may persist for several months after discharge. In addition to
      severity and duration of initial organ failures, both neuromuscular inactivity
      and use of corticosteroids make an independent contribution of the neuromuscular
      abnormalities. Conversely, strict glycemic control may prevent neuromuscular
      abnormalities, although this needs to be confirmed in general ICU patients.
      SUMMARY: Avoiding complete neuromuscular inactivity, using corticosteroids with
      greater discernment, and closely monitoring blood glucose levels might be
      worthwhile avenues for research in prevention of neuromuscular abnormalities
      acquired in the most severely ill ICU patients. Investigations of the severity of
      the respiratory neuromuscular involvement are also warranted.

PMID- 15166852
TI  - Bibliography. Current world literature. Respiratory system.

PMID- 15166850
TI  - Critical care lessons from severe acute respiratory syndrome.
AB  - PURPOSE OF REVIEW: Severe acute respiratory syndrome (SARS) is a new disease that
      caused large outbreaks in several countries in the first half of 2003, resulting
      in infection in more than 8000 people and more than 900 deaths. During that time,
      a large body of literature rapidly emerged describing the clinical disease, the
      etiologic viral agent, and management options. This paper reviews the current
      status of this knowledge base, with particular reference to the critically ill
      patient. RECENT FINDINGS: Case series of patients from Hong Kong, China,
      Singapore, and Toronto have characterized the disease with remarkable uniformity.
      A similarly consistent picture of the SARS patient with respiratory failure has
      emerged from studies from Toronto and Singapore. Worldwide collaboration led to
      the rapid identification and gene sequencing of the etiologic virus, SARS-CoV.
      SUMMARY: SARS is a predominantly respiratory illness, spread through droplets
      from respiratory secretions and possibly via a fecal-oral route. A small number
      of "super-spreaders" appear to have contributed to the rapid proliferation of the
      disease. Infection control precautions are an essential component of management.
      Approximately 20% of patients develop progressive pulmonary infiltrates and
      respiratory failure, and the mortality rate is as high as 10%. Treatment
      strategies with antiviral agents such as ribavirin have not clearly demonstrated
      a benefit, but high-dose corticosteroids appear to be beneficial in patients with
      progressive disease. The recent outbreaks highlighted the potential for this
      disease to overwhelm critical care resources, by the volume of patients and loss
      of healthcare workers to illness and quarantine.

PMID- 15166851
TI  - Guidelines for community-acquired pneumonia in the ICU.
AB  - Community-acquired pneumonia remains a common and serious condition worldwide.
      Severe community-acquired pneumonia requiring ICU admission is a distinct entity
      with different pathogens, outcomes, and management. The mortality rate in severe
      community-acquired pneumonia can be more than 50%. Over the past decade, some
      international guidelines for the management of community-acquired pneumonia have
      been developed in an attempt to optimize patient care. These guidelines have
      developed prediction tools to direct clinicians in the management of community
      acquired pneumonia, including when to admit a patient to the ICU and selecting
      appropriate investigations and antimicrobial therapy. The individual
      recommendations of these guidelines and the guidelines as a whole require further
      studies.

PMID- 15166854
TI  - Surgical techniques for cesarean delivery: what are the best practices?

PMID- 15166855
TI  - From preop to postop: Cesarean delivery from the anesthesiologist's point of
      view.

PMID- 15166856
TI  - Epidemiology of epidural analgesia and cesarean delivery.

PMID- 15166857
TI  - Cesarean delivery: emphasis on the neonate.

PMID- 15166858
TI  - Cesarean delivery at the limits of neonatal viability.

PMID- 15166859
TI  - Cesarean delivery for suspected macrosomia: inefficient at best.

PMID- 15166860
TI  - Trial of labor after cesarean: so, what are the risks?

PMID- 15166862
TI  - The downside of cesarean delivery: short- and long-term complications.

PMID- 15166861
TI  - Cost-effectiveness of a trial of labor after previous cesarean delivery depends
      on the a priori chance of success.

PMID- 15166863
TI  - Childbirth and pelvic floor disorders.

PMID- 15166864
TI  - Ethical considerations in elective cesarean delivery.

PMID- 15166867
TI  - Treatment of osteoporosis.

PMID- 15166868
TI  - Views on recent trials and the future of hormonal therapy.

PMID- 15166869
TI  - Depression and hormone therapy.

PMID- 15166870
TI  - Skin and hormone therapy.

PMID- 15166871
TI  - Menopause and patient management.

PMID- 15166872
TI  - The role of sex steroid hormones in female sexual function and dysfunction.

PMID- 15166873
TI  - Menopausal changes, quality of life, and hormone therapy.

PMID- 15166874
TI  - Current controversies regarding the cardiovascular effects of hormone therapy.

PMID- 15166878
TI  - Intraoperative detection of carcinoid tumor of the ovary by gamma probe.
AB  - PURPOSE: To demonstrate the detection of carcinoid tumor of the ovary by gamma
      probe during surgery in a patient in whom the exact location of a metastatic
      tumor was uncertain. METHODS: Twenty-four hours after injection of 350 MBq (9.5
      mCi) I-123, an anterior image of the abdomen was acquired before surgery to
      demonstrate MIBG accumulation. Holding the ovary in the hand during the
      operation, a surgical gamma probe indicated the exact location of highest
      radioactivity. RESULTS/CONCLUSIONS: Intraoperative MIBG scanning is a useful
      noninvasive detection method to localize metastases of carcinoid in the ovary.
      This method should be used only when it is not clear where the area of increased
      activity is located in the body because there are certain costs involved.

PMID- 15166879
TI  - Drainage across midline to sentinel nodes in the contralateral axilla in breast
      cancer.
AB  - The authors report a case of recurrent breast carcinoma in the right chest in a
      patient who earlier had a right breast mastectomy. Injection of Tc-99m sulfur
      colloid into the lesion site in the right midchest revealed drainage to a very
      faint node in the contralateral axilla on the left, an unexpected site, and none
      to the ipsilateral axilla, the expected site. Disease was found in the left
      axilla in the sentinel nodes. Lymphoscintigraphy added valuable information in
      the management of this patient.

PMID- 15166880
TI  - Transient left ventricular dilatation in the absence of epicardial disease on
      angiography.
AB  - A 58-year-old woman with a previous anterior myocardial infarction, recurrent
      chest pain, transient adenosine-induced left ventricular dilatation but no
      apparent epicardial disease on angiography is presented. Transient ischemic
      dilatation during myocardial perfusion imaging, and the reported causes of
      transient left ventricular dilatation in the absence of epicardial disease, are
      discussed.

PMID- 15166881
TI  - The assessment of infarct size in postmyocardial infarction patients undergoing
      thallium-201 tomographic imaging is improved using attenuation correction.
AB  - PURPOSE: Attenuation correction (ATC) has been shown to improve the accuracy of
      thallium-201 single photon emission computed tomography (SPECT) for the detection
      and evaluation of patients with coronary artery disease. The purpose of this
      study was to evaluate the value of ATC for the assessment of infarct size in
      patients after myocardial infarction (MI). MATERIALS AND METHODS: Tl-201 SPECT
      with ATC was performed on 39 patients with 49 previous MIs. This was followed by
      radionuclide ventriculography for the assessment of global and regional left
      ventricular function. Uncorrected and corrected 24-hour redistribution SPECT
      images were analyzed for regional perfusion using a 5-point segmental scoring
      scale from 0 (normal) to 4 (absent) thallium uptake. RESULTS: The mean number of
      segments with scores of >1 and 2 was significantly higher without ATC than with
      ATC (5.3 +/- 3.6 vs. 3.5 +/- 3.6, P = 0.0001 for scores >1; 3.8 +/- 3.6 vs. 2.5
      +/- 3.0, P = 0.0001 for scores of >2, respectively). The mean total number of
      segments with scores of >1 assessed without ATC was significantly higher compared
      with that assessed with ATC (16.9 +/- 13.5 vs. 11.2 +/- 12.2, P = 0.0001).
      Evaluation without ATC demonstrated only a fair correlation between the SPECT
      parameters (number of segments with scores of >1 and >2, and total score of
      segments with scores of >1) and left ventricular regional and global function,
      whereas there was a clear improvement in all the parameters after ATC. With ATC,
      a decrease in infarct size was demonstrated in 27 of the 49 infarcts (55%).
      CONCLUSIONS: The improved correlation with left ventricular function indicates
      that SPECT imaging with ATC provides a more accurate assessment of infarct size
      in post-MI patients. The use of nonattenuation-corrected SPECT imaging
      overestimates infarct size in a majority of patients.

PMID- 15166883
TI  - Posterior cingulate hypoperfusion in Alzheimer's disease, senile dementia of
      Alzheimer type, and other dementias evaluated by three-dimensional stereotactic
      surface projections using Tc-99m HMPAO SPECT.
AB  - Hypoperfusion in the posterior cingulate cortex is thought to be useful for the
      early diagnosis of dementia of Alzheimer type (DAT). In the present study, we
      compared the incidence of posterior cingulate hypoperfusion in patients with
      Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT),
      and patients with other types of dementia, as evaluated by three-dimensional
      stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD
      patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other
      types of dementia patients. A SPECT study was performed 5 minutes after the
      injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP
      images were obtained with global normalization to perform the statistical
      analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers.
      Hypoperfusion was considered to be significant when the Z-score was over 2.5.
      Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in
      5 of 20 SDAT patients (25%), but in none of other type of dementia patients.
      Posterior cingulate hypoperfusion was considered to be a finding specific to DAT,
      and this finding was thought to be useful to diagnose DAT patients, especially
      for AD patients. However, it was considered to be difficult to diagnose early
      stage SDAT patients.

PMID- 15166884
TI  - Localization of in-111 white blood cells in rhabdomyolysis.

PMID- 15166882
TI  - Correlation between cervical uptake and results of postsurgical radioiodine
      ablation in patients with thyroid carcinoma.
AB  - OBJECTIVE: The objective of this study was to determine the relationship between
      cervical uptake after thyroidectomy and the success of treatment of cervical
      remnants with high-dose radioiodine (100 mCi). METHODS: Cervical uptake was
      retrospectively analyzed after total thyroidectomy and before treatment with
      radioactive iodine in 142 patients seen at our service who received 100 mCi
      iodine-131 and whose posttreatment scan only showed cervical uptake without
      distant metastases. The patients were divided into 5 groups according to the
      uptake result obtained before ablative therapy. RESULTS: Successful treatment,
      defined as stimulated thyroglobulin levels <5 ng/mL and a clean scan or only
      discrete cervical uptake (0.5%) 6 months to 1 year after surgery, was obtained as
      follows: patients with uptake <1% (n = 48) showed 95.8% treatment efficacy, those
      with uptake of 1-2% (n = 32) 94% efficacy, and those with uptake of 2-5% (n = 30)
      reached 83% success, whereas patients with uptake of 5-10% (n = 20) presented 70%
      efficacy, and treatment was successful in only 50% of patients with uptake >10%
      (n = 12). CONCLUSIONS: Postoperative measurement of cervical I-131 uptake could
      be a reasonable predictor of the success of the remnant ablation, and perhaps a
      guide in deciding the ablative dose of I-131, based on the inverse correlation
      between the uptake and ablation efficacy.

PMID- 15166885
TI  - F-18 FDG positron emission tomography demonstration of pulmonary carcinoid.

PMID- 15166886
TI  - Serial Ga-67 scintigraphic findings of adult onset Still's disease.

PMID- 15166888
TI  - Gallium uptake in pericardial fat necrosis.

PMID- 15166887
TI  - Prostatic metastases versus polycythemia on bone imaging.

PMID- 15166889
TI  - Diuretic renography in late occurrence of hematoma after renal transplantation.

PMID- 15166890
TI  - Diagnostic difficulty in interpretation of Tc-99m MAG3 dynamic renal scan:
      intrarenal reflux or delayed concentration function?

PMID- 15166891
TI  - Duplicated collecting system: not following Weigert-Meyer rule as a result of
      renal stone obstructing the lower ureteropelvic junction.

PMID- 15166893
TI  - Increased tc-99m tetrofosmin uptake in a mediastinal tumor during myocardial
      perfusion imaging.

PMID- 15166892
TI  - Tc-99m sestamibi localization of an ectopic mediastinal parathyroid tumor in a
      patient with primary hyperparathyroidism.
AB  - A 50-year-old woman presented with pain and tenderness in the right flank.
      Urogram and ultrasound demonstrated the presence of an 8-mm calculus in the right
      kidney. There were persistently elevated serum calcium levels ranging from 10.7
      11.4 mg/dL (normal range: 8.5-10.5) and borderline low serum phosphate levels of
      2.4-2.9 mg/dL (normal range 2.5-4.5). Serum albumin levels were normal. The
      patient's parathormone levels were elevated and a diagnosis of primary
      hyperparathyroidism was made. An MRI of the neck failed to reveal evidence of
      parathyroid pathology. Tc-99m sestamibi imaging demonstrated no abnormal
      parathyroid tissue in the neck, but clearly showed an abnormal focus in the
      anterior mediastinum.

PMID- 15166896
TI  - Current readings in nuclear medicine.

PMID- 15166895
TI  - Tc-99m bone scintigraphy of large knee joint effusions in osteoarthritis.

PMID- 15166897
TI  - The preparticipation evaluation: an opportunity for change and consensus.

PMID- 15166894
TI  - Spontaneous rupture of a choledochal cyst and the role of hepatobiliary
      scintigraphy.

PMID- 15166898
TI  - Preparticipation evaluation: an evidence-based review.
AB  - OBJECTIVE: To review available evidence establishing the validity of the
      preparticipation evaluation (PPE) as a method for screening health risk prior to
      participation in exercise and sport. Specific emphasis was placed on reviewing
      original research evaluating methods to screen participants for risk of sudden
      cardiovascular death. Literature on the current state of the PPE as a screening
      tool for athletic participation was examined. DATA SOURCES: Electronic databases
      were searched for articles relating to mass screening for sports participation
      and sudden cardiac death in athletes published up to January 2004. Databases
      searched included Medline (OVID Web, 1966-2004), PubMed (1966-2004), Sport
      Discuss (1975-2004), Current Contents, CISTI Source (1993-2004), Cochrane
      Database of Systematic Reviews, and EBM Reviews. Additional references from the
      bibliographies of retrieved articles were also reviewed. SELECTION CRITERIA: All
      study designs were retrieved, but only those studying athletes and/or student
      athletes under age 36 years were reviewed. Of the original research retrieved,
      the majority of the articles sought to establish incidence or prevalence of
      cardiovascular causes of sudden death in athletes or the validity of various
      screening tools. Original research articles seeking to establish the current use
      of the PPE in all its various forms were also reviewed. All of the articles
      selected for review consisted of type II, population-based data. DATA EXTRACTION
      AND SYNTHESIS: The initial literature search identified 639 papers. Of these, 310
      articles that met the selection criteria were reviewed, and 25 articles were
      identified as original research directly relating to the PPE. All of these
      contained type II evidence-population-based clinical studies. The majority of the
      literature on the PPE consists of type III evidence-case-based opinion papers and
      position papers from respected authors and sports medicine societies and reports
      of expert committees. This literature was also reviewed, but only original
      research relevant to the PPE is reported in this article. The majority of these
      studies examined cardiovascular diseases and screening procedures. RESULTS: The 5
      studies that assessed the format or effectiveness of the PPE concluded that it
      was inadequate. The format of the PPE is not standardized and does not
      consistently address the American Heart Association recommendations for
      cardiovascular screening history and physical exams. A variety of health care
      professionals, some without proper training, administer the PPE. The 12 original
      studies that looked at specific cardiovascular screening techniques were divided
      on the effectiveness of history, physical examination, electrocardiogram, and
      echocardiography for detecting cardiovascular risks for sudden death in athletes.
      CONCLUSIONS: A PPE is required by most sport organizations in America, but
      research as to its effectiveness is very limited. PPEs have been mandatory in
      Italy for many years, and we can draw on some the data recorded over this time.
      Otherwise, very few studies in America or elsewhere have been performed on the
      PPE process. The research available indicates that the PPE is not implemented
      adequately or uniformly. An opportunity exists to create a standardized,
      validated PPE that meets medical standards for quality and provides sensitive,
      specific screening of potential participants in sport and exercise.

PMID- 15166899
TI  - Preparticipation orthopedic screening evaluation.
AB  - OBJECTIVE: To review evidence-based support for the preparticipation orthopedic
      evaluation. DATA SOURCES/METHODS: Articles were reviewed that dealt with the
      sensitivity, specificity, and predictive value of the components of the
      standardized preparticipation orthopedic evaluation. In addition, studies
      describing musculoskeletal conditions/findings predictive of future injuries were
      sought through a PubMed search. RESULTS: The sensitivity of the evaluation
      questionnaire appears to be adequate, exceeding 90% in some studies. There is
      little or no published information documenting that the physical examination (1)
      approaches the questionnaire in either sensitivity or specificity or (2)
      identifies elements of value based on their association with future injuries or
      reinjuries. There are no readily discernible elements even in an expanded
      examination that are documented as being predictive of future problems.
      CONCLUSIONS: The current questionnaire and examination appear to fulfill
      adequately both legal and institutional requirements. Practitioners should be
      aware of the absence of data linking virtually any of the findings on the
      examination to either an increase or a decrease in the likelihood of future
      injuries. There is no evidence that increasing the scope of the examination would
      enhance its predictive value.

PMID- 15166900
TI  - Cardiovascular screening of athletes.
AB  - Cardiovascular screening of athletes is a challenging aspect of the
      preparticipation evaluation. While sudden cardiac death in young athletes is
      uncommon, preparticipation screening may identify some predisposing conditions
      that place individuals at increased risk. The most common pre-existing cardiac
      abnormalities in athletes causing sudden death in the United States are
      hypertrophic cardiomyopathy, congenital coronary anomalies, and Marfan syndrome.
      Preparticipation cardiovascular screening should pursue any history of cardiac
      symptoms or family history of premature cardiac disease, as well as abnormal
      cardiovascular physical findings. Positive findings should be investigated; an
      electrocardiogram, echocardiogram, or consultation with a specialist should be
      considered. Recommendations are then available to guide athletic participation
      according to the cardiovascular diagnosis.

PMID- 15166901
TI  - Screening of athletes for exercise-induced bronchoconstriction.
AB  - Exercise-induced bronchoconstriction (EIB) has a high prevalence in elite
      athletes, particularly endurance athletes, winter athletes and swimmers. Recent
      studies have shown that a clinical diagnosis of EIB has only a moderate
      sensitivity and specificity for EIB. This finding in conjunction with a recent
      ruling by the IOC-medical commission that all athletes competing in initially the
      2003 Winter Olympic Games in Salt Lake City, and now the 2004 Summer Olympic
      Games in Athens require objective evidence of EIB, support the need for bronchial
      provocation challenge tests in the diagnosis of EIB. The recommended bronchial
      provocation challenge test is the eucapnic voluntary hyperpnea (EVH) challenge;
      this challenge test has been shown to have both a high sensitivity and
      specificity for EIB. Pharmacological challenge tests, such as the methacholine
      challenge test, have been shown to have only a low sensitivity but high
      specificity for EIB in elite athletes, and are thus not recommended in the
      athlete with pure EIB. Exercise challenge tests performed both in the laboratory
      and field have a high specificity for EIB; however those in the laboratory have
      only a moderate sensitivity for EIB in elite athletes, whilst those in the field
      are limited by problems with standardization. The osmotic challenge tests, such
      as the hypertonic saline and newer inhaled dry powder mannitol challenge have
      both a high sensitivity and specificity for EIB, and may be used as an
      alternative to the EVH challenge.

PMID- 15166902
TI  - Preparticipation assessment for head injury.
AB  - OBJECTIVE: To determine the evidence base for recommendations regarding the pre
      participation screening for head injury. DATA SOURCES: The relevant literature
      was searched through the use of Medline (1966 to 2004), Google and Sport Discus
      (1975 to 2004) searches, hand searches of journals and reference lists and
      discussions with experts and sporting organisations worldwide. DATA
      SYNTHESIS/METHODS: Consensus recommendations are summarized. No formal
      statistical analysis is presented RESULTS: Although pre-participation
      examinations are widely performed, there are no evidence-based guidelines to
      direct physicians as to the minimum requirements for the baseline assessment of
      head injury. CONCLUSIONS: Expert consensus would suggest that a baseline
      neuropsychological examination, preferably using a computerised test battery,
      should be performed in order to guide return to play following subsequent
      concussive injuries. In addition, there are important medicolegal considerations
      in regard to the value of a documented assessment both at the start and end of an
      athlete's career with any team.

PMID- 15166903
TI  - Utility of hematological and iron-related screening in elite athletes.
AB  - OBJECTIVE: To determine the clinical and performance related utility of
      hematological and iron-related screening in elite athletes. DESIGN: Prospective
      cohort study. SETTING: The Department of Sports Medicine at the Australian
      Institute of Sport. PARTICIPANTS: Male and female elite athletes undergoing
      routine medical screening over a period of 2 to 3 years. INTERVENTION: Blood
      testing for hematological and iron-related biochemical variables. MEASURES: White
      blood cell count, red blood cell count, hemoglobin, hematocrit, mean cell volume,
      mean cell hemoglobin concentration, platelet count, percent hypochromic red
      cells, serum iron, ferritin, transferrin, and percent transferrin saturation.
      RESULTS: Eight female athletes (4.6%) had clinically relevant abnormal results, 6
      with an obvious explanation on clinical history and examination and 1 who was
      diagnosed with hemochromatosis following genetic testing. Eighty-nine (51.1%)
      female athletes had abnormal results that were not associated with obvious
      clinical signs or symptoms. Twenty-seven female athletes had a serum ferritin
      less than 30 ng/mL and were placed on iron supplementation. In male athletes, 5
      cases had screening abnormalities that were associated with illness or other
      factors identified during the clinical consultations. Nonclinically significant
      abnormalities in males were generally minor reductions in hemoglobin and/or
      hematocrit or minor alterations in red cell parameters. Five male athletes had a
      serum ferritin less than 30 ng/mL and were placed on iron supplementation.
      CONCLUSION: Screening for hematological and iron-related abnormalities in male
      athletes has a very low yield. Due to the critical nature of the effects of
      anemia and low serum ferritin on some aspects of performance, it is reasonable to
      perform a full blood count and a serum ferritin on male athletes entering an
      elite training program. Further testing should be performed on clinical grounds.
      In females, the yield is greater. Again, it is reasonable to perform a full blood
      count and a serum ferritin on female athletes entering an elite training program.
      In view of their greater risk of iron depletion and to assess the effect of
      increased training inherent in elite programs, this could be repeated at 6-month
      intervals, or an isolated measurement of serum ferritin could be performed.
      Further testing should be performed on clinical grounds.

PMID- 15166904
TI  - Preparticipation physical examination: selected issues for the female athlete.
AB  - OBJECTIVE: The purpose of this article was to examine the preparticipation
      examination (PPE) with regard to the female athlete. Ever-increasing
      participation of women in competitive sport has created a requirement for more
      gender-specific sport medicine knowledge. In particular, physicians and other
      health care professionals should be aware of the triad of disordered eating,
      amenorrhea (and other menstrual dysfunction), and osteoporosis (or altered bone
      mineral density) collectively described as the female athlete triad. Suggested
      additions to the standard PPE may help identify athletes at risk. DATA
      SOURCES/METHODS: A literature search was carried out using MEDLINE for years 1966
      to 2003, with keywords female athlete triad, PPE, female athlete, eating
      disorders, amenorrhea, and osteoporosis. Further studies were identified through
      reference lists. RESULTS: Better recognition and prevention of these problems is
      essential. At present, there is little evidence-based information available to
      guide the practicing clinician in this area. It remains to be determined which
      methods are the most sensitive and specific for detecting the triad disorders, as
      well as the most economical and time-efficient. CONCLUSIONS: The PPE offers an
      excellent opportunity to screen for these entities, as well to initiate early
      treatment. It is recommended that a standardized form (or part of the form) be
      developed for the female athlete.

PMID- 15166905
TI  - Role of the physician in childhood obesity.
AB  - OBJECTIVE: To suggest the role of the practicing physician in examining and
      treating childhood obesity. How should obesity be determined at clinical
      examination? Is there an obesity epidemic? What is the likely influence of
      obesity upon current and future health? What are the causes of obesity, and what
      does this imply for prevention and treatment? DATA SOURCES: Relevant articles in
      Medline and personal files. DATA SYNTHESIS: The 80th and 95th percentiles of body
      mass index and skinfold readings provide the most commonly accepted indices of
      overweight and obesity in the child. Over the last 20 years, the proportions of
      overweight and obese children have increased in both indigenous populations and
      most developed societies. Current methods of assessing physical activity and diet
      during childhood lack the precision to establish the primary cause of the obesity
      epidemic, but correlational analysis shows a close relationship between body fat
      content and a decline in daily energy expenditures. Immediate consequences of
      childhood obesity include an increased prevalence of atherosclerotic plaques,
      hypertension, and an adverse lipid profile, with a poor self-image that limits
      participation in physical activity. Tracking is such that many obese children
      become obese adults, and in consequence, the long-term risks of cardiovascular
      and all-cause deaths are increased. The prevention of obesity is easier than its
      cure. A combination of increased lifestyle activities, less sedentary behavior,
      and dietary modification seems the most effective approach. This should be
      supported by the use of behavioral modification techniques and changes in the
      urban environment that encourage an active lifestyle. CONCLUSIONS: The pediatric
      physician can contribute to the control of obesity by monitoring body mass index
      and skinfold thicknesses in all patients. Children above the 50th percentile of
      body fat need dietary modification and a greater amount of moderate physical
      activity. Physicians should also advocate quality daily physical education and an
      environment that encourages adoption of an active lifestyle.

PMID- 15166906
TI  - Screening of athletes: Australian experience.
AB  - OBJECTIVE: To present an overview of medical screening of athletes in Australia
      DATA SOURCES: Data was obtained from Australian sports physicians involved in
      elite national and professional programs. DATA SYNTHESIS/METHODS: The status in
      Australia of medical screening and in particular the Pre-participation
      Examination (PPE) was reviewed. RESULTS: The PPE as practised in North America is
      not performed in Australia. However medical screening of elite national level and
      professional athletes is widely practised. A variety of screening methods is
      used. The medical screening protocol recently developed on behalf of the
      Australasian College of Sports Physicians (ACSP) is presented. CONCLUSIONS:
      Medical screening of high performance athletes takes place regularly in
      Australia. Valuable information may be obtained from this process. The extent of
      the screening is limited by financial and time constraints. The proposed protocol
      is a basis for a comprehensive medical screening, but can be adapted depending on
      the individual and the sport played.

PMID- 15166907
TI  - Preparticipation examination (screening): practical issues as determined by
      sport: a United Kingdom perspective.
AB  - OBJECTIVES: Pre-participation examination, screening and health surveillance are
      part of the job specification for many roles within Sports Medicine. The type and
      scope of this activity varies enormously, with little consensus as to best
      evidence-based practice. The purpose of this work was to explore and understand
      the practical approaches to pre-participation examination, screening and health
      surveillance in two contrasting sport scenarios. DATA SOURCE: Team physicians for
      British Triathlon and Manchester United Football Club. DATA SYNTHESIS/METHODS:
      Information was gathered under the headings: why screen, screening objectives,
      practical issues and constraints? RESULTS: The systems evolved within these two
      sports reflect their respective opportunities and constraints. Different systems,
      each with merit, have evolved with some generalizable concepts across sport.
      CONCLUSIONS: A perfect system for pre-participation examination, screening and
      health surveillance across all sport does not exist, however, within specific
      sport scenarios examples of good practice are demonstrated.

PMID- 15166908
TI  - Optimizing the collegiate preparticipation physical evaluation.
AB  - BACKGROUND: Today's collegiate student athlete is a highly diverse individual and
      as such is at higher risk for many health problems both on and off the field.
      OBJECTIVE: To determine if a preparticipation evaluation (PPE) can be optimized
      to help the collegiate team physician and athletic trainer assess both current
      and past health issues of student athletes. DATA SOURCES: Utilizing MEDLINE and
      other medical literature database search engines, the authors conducted detailed
      literature searches on this subject. Key words used in these searches included
      preparticipation physical evaluation, collegiate, athlete, cardiovascular,
      preventive healthcare, high risk, alcohol, tobacco, sexually transmitted disease,
      motor vehicle accident, adolescent, and female. METHODS: Approximately 35
      articles were selected for review for this report. Authors reviewed articles
      within their particular area of content responsibility. Personal communications
      with several sports medicine experts were also conducted. RESULTS: Twenty-three
      articles were selected for inclusion, in addition to information obtained from
      the American College of Sports Medicine and National Collegiate Athletic
      Association (NCAA) Web sites. Utilizing these sources, as well as guidance and
      suggestions from other sports medicine physicians, the authors determined that
      the NCAA-mandated PPE should deliver an overview of the athlete's entire health
      status. CONCLUSIONS: As detailed in this report, it is recommended that the NCAA
      PPE serve as a tool in tracking and assessing both current and past health issues
      of student athletes. These health issues would include (1) on-field health
      concerns such as cardiac and musculoskeletal conditions, (2) off-field health
      concerns (that may adversely impact on-field performance) such as sexual activity
      and substance abuse, and (3) health issues unique to the female student athlete,
      such as eating habits, nutritional record, and menstrual history. Primary care
      physicians should be involved in all PPEs as they have the necessary expertise to
      recognize potential problems in these areas.

PMID- 15166909
TI  - Efficacy and safety of ephedra and ephedrine for weight loss and athletic
      performance.

PMID- 15166910
TI  - Leisure-time physical activity and progression of carotid atherosclerosis.

PMID- 15166911
TI  - Cardiorespiratory fitness and the risk of stroke in men.

PMID- 15166912
TI  - Risks of injury during intercollegiate basketball.

PMID- 15166914
TI  - Assessing aspirin responsiveness in subjects with multiple risk factors for
      vascular disease with a rapid platelet function analyzer.
AB  - Aspirin, compared with placebo, reduces the risk of cardiovascular events by 25%
      in populations of patients with and without known arterial vascular disease.
      However, the phenomena of 'aspirin resistance' that has been described in 5'--50%
      of this population may critically reduce aspirin's efficacy. One study has
      suggested that aspirin-resistant patients have a 3.5 times higher risk of
      cardiovascular death. Presently, there are no established, simple, broadly used
      methods determining antiplatelet properties of aspirin, while conventional
      aggregometry requires special equipment and trained personnel. We sought to
      determine the validity of an Ultegra analyzer with the novel aspirin-sensitive
      cartridge before and after one pill of non-enteric coated aspirin (325 mg) in
      subjects with multiple risk factors for coronary artery disease. One hundred and
      fifty-four volunteers were enrolled into the multicenter study, but six of them
      were excluded. Data from 148 participants were analyzed. Platelets were assessed
      twice at baseline (pre-aspirin), and after 2-30 h (post-aspirin). We employed 5
      micromol/l epinephrine-induced conventional aggregometry, and aspirin response
      units stimulated by propyl gallate with the point-of-care Ultegra analyzer. A
      single pill of aspirin reduced platelet-rich plasma aggregation from 72 +/- 21%
      to 25 +/- 10%, and diminished aspirin reduction units from 647 +/- 95 to 436 +/-
      69. The overall agreement between the two methods was 87% with 85% sensitivity
      for Ultegra and 88% for platelet aggregation, respectively. The correlation
      between the two methods was 0.902. Timely determination of aspirin resistance
      represents an indispensable application in current medicine. The Ultegra RPFA-ASA
      analyzer is a novel, fast method that could be used in clinical practice for
      monitoring efficacy of aspirin, and for triaging the aspirin-resistant
      population. The clinical implications of these data need to be proven in
      randomized trials.

PMID- 15166913
TI  - Biophysical characterization of fibrinogen Caracas I with an Aalpha-chain
      truncation at Aalpha-466 Ser: identification of the mutation and biophysical
      characterization of properties of clots from plasma and purified fibrinogen.
AB  - Fibrinogen Caracas I is a dysfibrinogenemia with a mild bleeding tendency; a
      novel nonsense mutation, in the gene coding the Aalpha-chain, identified in this
      study as G4731T, giving rise to a new stop codon at Aalpha-Glu 467. Fibrinogen
      from two family members, the mother and sister of the propositus, both
      heterozygous for the mutation were studied, analyzing clots made from both plasma
      and purified fibrinogen. Clot structure and properties were characterized by
      turbidity, permeation, scanning electron microscopy and rheological studies.
      Permeation through Caracas I plasma clots was decreased, consistent with the
      decreased final turbidity. As shown by scanning electron microscopy, plasma clots
      from the patients were composed of very thin fibers, with increased fibrin
      density and reduced pore size. Viscoelastic measurements revealed that fibrinogen
      Caracas I plasma clots were much stiffer and less subject to compaction. These
      results demonstrate a key role of the carboxyl-terminal alpha chains of fibrin in
      lateral aggregation during polymerization and reinforce the utility of studying
      plasma clots. It is important to point out that the biophysical studies with
      fibrinogen purified by two different methods yielded contradictory results, which
      can be accounted for by selective purification of certain molecular species as
      seen by two-dimensional electrophoresis.

PMID- 15166915
TI  - Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on
      bleeding time and coagulation: a randomized, placebo-controlled, double-blind
      study in healthy volunteers.
AB  - During recent years, several case reports have been published in which the
      authors have voiced their suspicion of a causal relationship between hemorrhagic
      complications and the intake of Ginkgo biloba preparations. Therefore, a trial
      was conducted to investigate the influence of Ginkgo biloba special extract EGb
      761 on hemostasiological parameters. Fifty healthy, male volunteers underwent 7
      days of crossover treatment with 2 x 120 mg/day EGb 761 and placebo in randomized
      sequence. Between the two treatment phases, a washout-period of at least 3 weeks
      was inserted. The study's main outcome measures were bleeding time, coagulation
      parameters, platelet activity in response to various agonists and platelet
      morphology. The equivalence of the two treatments was analyzed by computing the
      90% Fieller confidence intervals for the ratio between the means of the pre-post
      treatment differences for EGb 761 and placebo, respectively. Treatment safety was
      investigated by clinical laboratory and vital signs assessment and by adverse
      events monitoring. Among the 29 coagulation and bleeding parameters assessed,
      none showed any evidence of an inhibition of blood coagulation and platelet
      aggregation through EGb 761. Furthermore, the study did not reveal any evidence
      to substantiate a causal relationship between the administration of EGb 761 and
      hemorrhagic complications. As regards treatment tolerability, there were no
      interpretable differences between EGb 761 and placebo except for a slight
      increase of gastrointestinal complaints during administration of the herbal
      extract.

PMID- 15166916
TI  - Pre-existing anticardiolipin antibodies and development of restenosis after
      coronary balloon angioplasty: predictive value for a complicated course?
AB  - Immune mechanisms play a critical role in cardiovascular disease. Cardiolipins
      are candidate autoantigens with a prothrombotic activity of their corresponding
      antibodies. We investigated the influence of pre-existing immunoglobulin (Ig)M
      and IgG anticardiolipin (aCL) antibodies on restenosis after coronary balloon
      angioplasty and their interaction with tissue plasminogen activator, plasminogen
      activator inhibitor type-1, von Willebrand factor and lipoprotein (a) in 132
      patients with stable angina pectoris using immunoassays. Thirty percent of
      patients developed angiographically proven restenosis estimated by three
      independent experienced angiographers; 12% of all patients developed recurrent
      restenoses at the same site during a follow-up period of 2 years. Circulating IgM
      aCL antibodies categorized by quartiles predicted recurrent restenoses (logistic
      regression, for trend P < 0.04) with an increase of relative risk (RR) per
      quartile of 2.09. The predictive value of IgM aCL antibodies was unchanged
      adjusting for established cardiovascular risk factors (P = 0.028, RR = 2.69),
      extent of coronary artery disease (P = 0.014, RR = 2.73) and inflammatory
      parameters (P = 0.025, RR = 2.79), but lost significance adjusting for other
      prothrombotic parameters (P = 0.24, RR = 1.76). IgM aCL antibodies positively
      correlated with lipoprotein (a) (r = 0.23, P = 0.04). However, there was no
      significant interaction between their influences on recurrent restenoses. The
      other prothrombotic parameters did not predict single or recurrent restenoses. In
      conclusion, IgM aCL antibodies may help to identify a group of patients at high
      risk for recurrent restenoses after coronary balloon angioplasty.

PMID- 15166917
TI  - Exercise-induced activation of coagulation in subjects with activated protein C
      resistance.
AB  - In the healthy individual intensive physical exercise leads to a minor activation
      of blood coagulation that appears to be balanced by a concomitant activation of
      the fibrinolytic system. This study tested the hypothesis that vigorous exercise
      might give rise to an exaggerated activation of coagulation in subjects with
      resistance to activated protein C (APC). Molecular markers of thrombin
      (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes) and fibrin
      formation (fibrinopeptide A), as well as markers of the fibrinolytic activity
      (plasmin-antiplasmin complexes, D-dimers), were determined in nine asymptomatic
      male individuals with APC resistance [age, 18 +/- 3 years; maximal oxygen
      consumption, 56.7 +/- 2.7 ml/kg per min (mean +/- standard deviation)] and in
      nine male control subjects (age, 19 +/- 4 years; maximal oxygen consumption, 56.2
      +/- 3.2 ml/kg per min) after 1 h of running to exhaustion. Baseline levels of
      prothrombin fragment 1 + 2 were higher in individuals with APC resistance than in
      controls [0.67 +/- 0.06 nmol/l (mean +/- standard error) versus 0.48 +/- 0.01
      nmol/l; P < 0.05]. In response to exercise, hemostatic variables significantly
      increased in both groups to a similar small extent. Likewise, exercise-induced
      changes of fibrinolytic variables in subjects with APC resistance paralleled
      those observed in controls. In summary, exhaustive running in subjects with APC
      resistance does not provoke an abnormal hemostatic or fibrinolytic response,
      suggesting that vigorous exercise does not imply an increased risk for thrombosis
      in young male subjects with APC resistance.

PMID- 15166918
TI  - Bleeding prophylaxis for major surgery in patients with type 2 von Willebrand
      disease with an intermediate purity factor VIII-von Willebrand factor concentrate
      (Haemate-P).
AB  - The parameters to diagnose von Willebrand disease (vWD) include factor VIII
      coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), von
      Willebrand factor ristocetin cofactor activity (vWF:RCo), and von Willebrand
      factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a
      moderate bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared
      with near normal or normal values for FVIII:C and vWF:Ag. As the factor VIII/von
      Willebrand factor (vWF) concentrate, Haemate-P, is featured by a vWF:RCo/FVIII:C
      ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by
      25 U/kg FVIII:C every 12 h for several days for bleeding prophylaxis in type 2
      vWD patients undergoing major surgery demonstrated a predicted significant over
      treatment reaching vWF:RCo levels above 2 U/ml. Therefore, we restricted Haemate
      P substitution for major surgery to one loading dose of 40-50 U/kg FVIII:C (88
      110 U/kg vWF:RCo) followed by 15-20 U/kg FVIII:C (33-44 U/kg vWF:RCo) every 12 h
      for several days and evaluated this strategy in a prospective pharmacokinetic and
      efficacy study for bleeding prophylaxis in five type 2 vWD patients. Pre
      treatment and peak levels (1 h after Haemate-P loading dose) rose from 0.43-0.66
      to 1.5-2.5 U/ml for FVIII:C, from 0.23-0.45 to 1.5-2.5 U/ml for vWF:Ag, from 0.10
      < 0.20 to 1.5-2.5 U/ml for vWF:RCo, and from < 0.05-0.10 to 1.0-2.0 U/ml for
      vWF:CB. Mean in vivo recoveries per transfused IU FVIII:C/kg body weight were
      3.2% for FVIII:C, 3.9% for vWF:RCo, and 2.8% for vWF:CB. Mean in vivo recoveries
      per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25%
      for vWF:CB. The biological half-life times after transfused Haemate-P were about
      12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose
      to adapt the loading dose factor VIII/vWF concentrate (Haemate-P) to 60-80 U/kg
      vWF:RCo followed by 30-40 U/kg vWF:RCo every 12 h for no longer than several days
      (less than 1 week) for bleeding prophylaxis during major surgery or trauma, and
      to one loading dose of 40-60 U/kg vWF:RCo for minor surgery, trauma or
      mucotaneous bleedings in patients with type 2 vWD unresponsive to DDAVP.

PMID- 15166919
TI  - Low-grade and high-grade fever at presentation of acute pulmonary embolism.
AB  - We retrospectively reviewed the medical records of 154 consecutive patients with
      acute pulmonary embolism (PE) admitted to an Internal Medicine Service. At
      presentation, fever (temperature > 37 degrees C) without other identified causes
      was present in 28 patients (18.2%): 27 patients had low-grade fever (temperature
      37-39 degrees C) and one patient had high-grade fever (temperature > 39 degrees
      C). Epidemiological and clinical characteristics, electrocardiographic and chest
      radiograph abnormalities and mortality rate were similar in patients with and
      without fever. Fever, including high-grade fever, is a possible presenting
      feature in patients with acute PE. Patients with acute PE and fever have similar
      characteristics compared with those without fever.

PMID- 15166920
TI  - The use of recombinant activated factor VII for controlling life-threatening
      bleeding in Dengue Shock Syndrome.
AB  - To report the use of recombinant activated factor VII (rFVIIa) in controlling
      life-threatening bleeding episodes in patients with grades III and IV Dengue
      Hemorrhagic Fever (DHF), also known as Dengue Shock Syndrome. Fifteen patients
      (seven boys, eight girls), whose median age was 8 years, were enrolled in the
      study. They were divided into two groups. Group 1 included nine patients, mainly
      grade III, waiting for platelet concentrate, and group 2 included six patients,
      mainly grade IV, who had already received platelet concentrate with
      unresponsiveness. A single dose or repeated doses of 100 microg/kg rFVIIa
      was/were given at intervals of 4 h according to the bleeding symptoms. The median
      times from the onset of bleeding to rFVIIa initiation were 6.5 and 29.8 h in
      groups 1 and 2, respectively. Each patient received one to three doses. An
      effective response was found in eight patients (53.3%), including six patients in
      group 1 and two patients in group 2. They had complete cessation of bleeding
      without recurrence for 48 h. An ineffective response was found in seven patients
      (46.7%) including three patients in group 1 and four patients in group 2 for
      which the bleeding recurred (n = 2), temporarily slowed down (n = 3), continued
      (n = 1) or occurred at a new site (n = 1). These included three patients in
      profound shock 24-48 h before referral to comprehensive treatment centers, two
      patients receiving ibuprofen before hospitalization, one patient with extensive
      volume overloading, and one patient requiring surgical intervention to ligate the
      torn intercostal artery and vein. The platelet concentrate was promptly
      transfused to stop bleeding in patients with ineffective responses. The results
      revealed that the earlier initiation of rFVIIa in the mainly grade III DHF in
      group 1 yielded a higher effective response (66.7%) than the delayed initiation
      in the mainly grade IV DHF in group 2 (33.3%). Moreover, patients previously
      receiving ibuprofen or volume expander of low molecular weight dextran or urea
      linked gelatin tended to have lower effective responses (28.6%) than patients
      without associated medication (75.0%). Ultimately, three of six patients with
      grade IV DHF died, while all nine patients with grade III DHF survived. Thus, the
      case-fatality rate in this study was 20%. No clinical evidence of thromboembolic
      complications was observed. rFVIIa seems to be effective in restoring hemostasis
      in a limited series of patients with Dengue Shock Syndrome exhibiting life
      threatening bleeding episodes. Further study is warranted.

PMID- 15166921
TI  - Clinical and laboratory evaluation of Turkish children with thrombosis for
      homozygous factor V G1691A mutation.
AB  - Factor V (FV) G1691A mutation, in a heterozygous state, is one of the most common
      inherited risk factors for development of thrombosis. However, the clinical
      manifestations of homozygosity for the FV G1691A mutation in children is largely
      unknown because of the limited number of studies reported. The purpose of this
      study was to evaluate the clinical manifestations and laboratory findings of
      children with thrombosis who were homozygous for this mutation. Ten patients
      (four male/six female; mean age, 4.5 years; age range, 1-13 years) who were found
      to be homozygous for the FV G1691A mutation among 360 consecutive children with
      thrombosis (2.8%) were the subjects of this study. Six of the 10 patients had
      venous thrombosis, two had purpura fulminans, one had diffuse skin ecchymosis and
      one had arterial thrombosis. No history of thrombosis was present in their family
      members. Seven of the 10 children were under the age of 5 years. One or more
      additional risk factors (infection, protein S and protein C deficiencies,
      elevated factor VIII, etc.) were also present in nine of these patients. None of
      these patients had prothrombin G20210A mutation but one patient had risk
      associated plasminogen activator inhibitor-1 gene 4G/4G genotype. These findings
      suggest that, in the presence of other underlying risk factors, homozygosity for
      FV G1691A mutation may lead to development of thrombosis at a very young age.

PMID- 15166922
TI  - Acquired isolated factor VII deficiency associated with severe bleeding and
      successful treatment with recombinant FVIIa (NovoSeven).
AB  - Acquired isolated FVII deficiency not due to vitamin K deficiency or liver
      disease is rare and often associated with severe bleeding. We present a case of
      transient acquired factor VII deficiency associated with major bleeding,
      successfully treated with twice daily intermittent intravenous recombinant
      activated factor VII (rFVIIa) (NovoSeven; Novo Nordisk). The severe transient
      reduction in factor VII coagulant activity (FVII:C) levels, unresponsive to fresh
      frozen plasma and vitamin K administration, raise the possibility of an acquired
      inhibitor to factor VII. However, no inhibitor to factor VII could be
      demonstrated using protein G sepharose adsorption, or a Bethesda assay using IgG
      purified from patient plasma. There are few reports of the use of rFVIIa in this
      setting and this case suggests that rFVIIa is effective therapy, and should be
      considered early when acquired factor VII deficiency is associated with severe
      bleeding.

PMID- 15166923
TI  - Evaluation of the phospholipid-rich dilute Russell's viper venom assay to monitor
      oral anticoagulation in patients with lupus anticoagulant.
AB  - The International Normalized Ratio (INR) is generally recommended to monitor
      anticoagulant therapy in patients treated with warfarin. However, there has been
      concern about the validity of the INR to monitor warfarin therapy in patients
      with lupus anticoagulant, particularly when there is prolongation of the baseline
      INR. An alternative approach is to use a chromogenic factor X assay that is not
      sensitive to lupus anticoagulant. However, this assay is expensive, not widely
      available, and does not have an established therapeutic range. We hypothesized
      that the phospholipid-rich dilute Russell viper venom time (prdRVVT), a simple,
      rapid and inexpensive assay, might be suitable to monitor warfarin therapy in
      this situation since Russell's viper venom directly activates coagulation factor
      X while the phospholipid in the reagent reduces or negates any effect of lupus
      anticoagulant on the assay. We measured the INR, chromogenic factor X, and
      prdRVVT in 50 patients stabilized on warfarin for at least 6 weeks, 12 of whom
      had lupus anticoagulant, and 37 patients not taking warfarin, 17 of whom had
      lupus anticoagulant. Factor X was negatively correlated with INR in
      anticoagulated patients both in the absence (r = -0.45, P = 0.01) and presence (r
      = -0.43, P = 0.17) of lupus anticoagulant. The prdRVVT was also strongly
      correlated with INR in anticoagulated patients without lupus anticoagulant (r =
      0.60, P < 0.0001) but there was no correlation in the presence of lupus
      anticoagulant (r = -0.13, P = 0.68). Our results suggest that the prdRVVT is not
      suitable for monitoring warfarin therapy in patients with lupus anticoagulant.

PMID- 15166924
TI  - Fibrin glue in initial treatment of epistaxis in hereditary haemorrhagic
      telangiectasia (Rendu-Osler-Weber disease).
AB  - The purpose of the present study was to evaluate the haemostatic efficacy of
      fibrin sealant in patients with hereditary haemorrhagic telangiectasia (HHT) or
      Rendu-Osler-Weber disease suffering epistaxis. A retrospective observational
      study of patients with HHT who were admitted to an emergency room for anterior or
      posterior epistaxis during May 2000-March 2003. A total of 24 patients were
      evaluated, of whom 15 were managed with foam nasal packing during May 2000-March
      2002 and another nine were treated during March 2002-March 2003 with 0.3 ml
      fibrin sealant spray (Quixil; Omrix, Belgium). The immediate and the distant
      results were compared. Immediate haemostasis was achieved in all seven patients
      treated with fibrin glue, with good healing of bleeding sites, no secondary
      bleeding, no inflammation, and no plaque or crists. Twelve months of follow-up
      monitoring (until October 2003) of atrophic changes of nasal mucosa, bleeding
      frequency and intensity proved absence of atrophy of nasal mucosa and decreased
      bleeding frequency. In this group, the bleeding episode duration averaged 2 min
      35 s since the moment of admittance. In the nasal packing group, we found local
      swelling, pain, and slow healing of the bleeding site with accidental atrophy of
      nasal mucosa and no effect on further bleeding frequency and intensity. Removal
      of nasal packing frequently initiates secondary bleeding. The rates of these side
      effects were higher in comparison with the fibrin glue group. The bleeding
      episode duration was also longer. In patients with HHT suffering profuse
      epistaxis, fibrin glue is more effective and convenient for the patients as
      compared with foam nasal packing. It is also safer, since it lacks the
      complications that usually accompany packing as swelling, atrophy of the nasal
      mucosa, and secondary bleeding provoked by the removal of the pack.

PMID- 15166925
TI  - Association of the -159C --> T polymorphism in the CD14 promoter with variations
      in serum lipoproteins in healthy subjects.

PMID- 15166927
TI  - Tissue factor: from 'just one of the coagulation factors' to a major player in
      physiology.
AB  - As early as the nineteenth century, it was recognized that tissues exhibit clot
      promoting activity. The realization that a single protein was responsible for
      this procoagulant effect led to the discovery of tissue factor (TF), but for many
      years it was thought that TF activity was restricted to the activation of an
      auxiliary pathway that had little biological relevance. Research over recent
      decades has greatly improved our understanding of TF function, and today the
      protein is recognized to be the primary biological initiator of the coagulation
      cascade. Furthermore, it is now clear that TF is a major player in several other
      physiological processes. We present recent data suggesting that TF is vital not
      only for effective haemostasis, but also for angiogenesis and tumour metastasis,
      for embryonic development, and for induction of a pro-inflammatory response.
      These advances in our knowledge of TF function will improve our understanding of
      several pathophysiological conditions, and may expand the therapeutic options
      available for their treatment.

PMID- 15166928
TI  - Role of the tissue factor pathway in the pathogenesis and management of multiple
      organ failure.
AB  - Sepsis is caused by a dysregulated immune response to infection and, without
      intervention, can lead to septic shock and multiple organ failure. A leading
      cause of morbidity and mortality in intensive care units worldwide, severe sepsis
      is also associated with a considerable cost burden that places significant strain
      on global healthcare budgets. The development of an efficacious and cost
      effective treatment strategy is therefore of vital importance to today's
      intensive care physicians. This paper will examine the pathophysiology of sepsis
      and multiple organ dysfunction before reviewing trials recently undertaken to
      investigate three potential anticoagulant therapies: antithrombin III, activated
      protein C, and tissue factor pathway inhibitor. Finally, other recent
      developments in the care of sepsis patients will be briefly examined.

PMID- 15166929
TI  - Type 1 von Willebrand disease: a possible novel mechanism.
AB  - ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs) catalyses
      the proteolysis of von Willebrand factor (vWF). Recent research has indicated
      that the rate of vWF proteolysis by ADAMTS13 is greater for group O than non-O
      groups, in the order: group O >/= group B > group A >/= group AB. This, together
      with the observation that vWF levels are lower for group O than non-O groups,
      suggested a possible inverse relationship between vWF proteolysis and vWF level.
      We studied four patients with von Willebrand disease type 1 and found that the
      ADAMTS13 activity in their cryo-depleted plasma was similar and comparable with a
      normal control. In contrast, the vWF from one patient was significantly more
      susceptible to proteolysis than that of the others, which were comparable with a
      normal control. The increased susceptibility to proteolysis was associated with
      heterozygosity for tyrosine/cysteine 1584 (Tyr/Cys1584). A preliminary cohort
      study (n = 200) indicated an allele frequency of 0.005 for G 24/1282 encoding
      Cys1584. In vitro, heterozygous vWF showed an increase in proteolysis of 13.1
      23.5% compared with homozygous Tyr/Tyr vWF. These data suggest that increased vWF
      proteolysis may be implicated in type 1 von Willebrand disease in some patients
      and that Cys1584 may, in part, exert its effect through this mechanism.

PMID- 15166930
TI  - Systematic review of the management of patients with haemophilia A and
      inhibitors.
AB  - The London Directorate of Health and Social Care Research and Development Group
      recently commissioned the School of Health and Related Research at the University
      of Sheffield to perform a systematic review of the management of patients with
      haemophilia A and inhibitors. The main areas of the review were the epidemiology
      of inhibitors, the role and effectiveness of immune tolerance induction, and the
      control of acute bleeding. In addition, an economic model of the different
      treatment strategies was constructed. Among the findings was that the overall
      prevalence of inhibitors in unselected haemophilic populations is 5-7%, with the
      cumulative inhibitor risk varying from 0% to 39%. The prevalence of inhibitors
      was inversely related to the size of the reported population. Immune tolerance
      induction was considered desirable, with evidence suggesting that the Bonn
      protocol may be more effective than either the Malmo or low-dose protocols.
      Immunosuppressive drug regimens on their own were ineffective. Activated
      prothrombin complex concentrates (aPCC) were more effective than non-aPCC.
      Recombinant activated factor VII was also effective, but there were no randomized
      trials comparing this agent with aPCC. Porcine factor VIII was highly effective
      in both treating acute bleeding episodes and preventing bleeding after surgery.

PMID- 15166931
TI  - The European acquired haemophilia registry.
AB  - Acquired haemophilia is a rare bleeding disorder, occurring in approximately one
      person in every million. The mortality from bleeding is approximately 20%. The
      development of autoantibodies to factor VIII is commonly associated with the
      postpartum period, the presence of other autoimmune disorders, malignancy,
      lymphoproliferative disorders and previous multiple transfusions. Nevertheless,
      all these observations are based on a number of rather small case series. In
      2001, the United Kingdom Haemophilia Centre Doctors' Organisation initiated a 2
      year registry across the UK to provide more robust information on the incidence
      and clinical features of acquired haemophilia. This registry enrolled almost 200
      patients. Analysis and publication of these data are underway. In order to
      collect data across Europe, the European Acquired Haemophilia Registry has
      recently been initiated. The Registry is run by an independent steering committee
      consisting of specialists in the field of acquired haemophilia, and collects data
      on clinical features and management of the patients, using a secure, Internet
      based platform. All clinicians who treat patients with acquired haemophilia are
      encouraged to enrol consenting patients in the Registry. The data obtained in the
      Registry will provide a better understanding of acquired haemophilia, and may
      contribute to improving the treatment.

PMID- 15166932
TI  - Recombinant activated factor VII in cardiac surgery.
AB  - Adult cardiac surgery has an incidence of 1-1.25 million procedures per year.
      Overall costs are in the range of 50 billion US dollars per year and are
      increasing. Included in these costs is an increasing burden from the use of blood
      and blood products. The central haemostatic problems associated with cardiac
      surgery are impaired platelet function associated with pre-operative medication
      and cardiopulmonary bypass, consumption of platelets, dilution of coagulation
      proteins and triggering of fibrinolysis. Anecdotal data suggest that recombinant
      activated factor VII (rFVIIa) has a possible role in cardiac surgery, but
      randomized, controlled trials are required to confirm this potential. We have
      undertaken a prospective, randomized, placebo-controlled trial in adult cardiac
      surgery with a high risk of serious haemorrhage. Drug (rFVIIa) or placebo is
      given after cardiopulmonary bypass and following the administration of protamine.
      The primary endpoints of the study are use of blood and blood products. Secondary
      endpoints are blood loss, length of stay in the intensive care unit and in the
      hospital, and survival. This study will give us further information on the
      potential efficacy and safety of rFVIIa in cardiac surgery.

PMID- 15166933
TI  - Bruising, coagulation disorder, and physical child abuse.
AB  - Child protection is a priority, and the medical community has a responsibility to
      detect cases of abuse and to intervene using the appropriate measures. Bruises
      are the most common manifestation of physical abuse, although their
      interpretation can be extremely challenging for paediatricians as the evidence
      base is limited. As a history of abuse is a strong risk factor for further non
      accidental injury, a correct diagnosis is vital. Clearly, the diagnostic process
      must determine whether an underlying coagulation disorder exists. It is important
      to realize, however, that the presence of a coagulation deficit does not
      necessarily exclude abuse. A growing body of evidence suggests that the practice
      of estimating bruise age is unreliable; therefore, a key factor in diagnosing
      abuse is the pattern of bruise distribution, which must be linked to the child's
      history and stage of development. The paediatrician must also consider the
      combined probabilities of individual bruises being due to abuse. Our scoring
      system, which uses a Bayesian approach to evaluate these probabilities and assess
      bruising patterns, is a potentially useful tool for discriminating between abused
      and non-abused children. We recommend that paediatricians and haematologists
      should work together to reach a diagnostic consensus that is acceptable in both
      the clinic and a court of law.

PMID- 15166934
TI  - Non-accidental injury and the haematologist: the causes and investigation of easy
      bruising.
AB  - In cases of suspected non-accidental injury in children, it is vital that a
      haematologist confirms the presence or absence of a haemostatic disorder so that
      the child welfare and legal systems can make accurate judgements regarding the
      cause of isolated injuries. The present paper will discuss commonly used methods
      for the diagnosis of coagulation disorders in children, and will describe how the
      investigation of easy bruising and bleeding can be highly problematic. For
      instance, some frequently used tests for the assessment of haemostasis in
      children are insensitive, inappropriate, or based on values derived from adult
      populations. Furthermore, artefact is a frequent problem, and many cases present
      with a negative family history of bleeding. Therefore, the role played by the
      haematologist in potential child abuse cases is an essential yet challenging one.

PMID- 15166936
TI  - The effect of hormone replacement therapy on Ca2+ mobilization and P-selectin
      (CD62P) expression in platelets examined under flow cytometry.
AB  - A series of events, such as increase of cytoplasmic free calcium (Ca2+) and
      expression of P-selectin (CD62P), an adhesion molecule, on the platelet surface,
      are significant indicators of platelet activation. We have used flow cytometry to
      examine Ca2+ mobilization and CD62P expression in platelets in whole blood
      obtained in women prior to, and after, different forms of hormone replacement
      therapy. Thirty-two women completed a protocol consisting of two consecutive 1
      month periods under oestradiol (E2), administered orally (2 mg/day) or
      transdermally (50 microg/day) in random order, followed by a 4-week transdermal
      sequential regime, in which, during the last 14 days, either progesterone (300
      mg/day) or medroxyprogesterone acetate (5 mg/day) was added to the 50 microg/day
      E2, administered orally in random order. None of the hormonal combinations
      determined significant changes in Ca2+ mobilization or CD62P expression in non
      stimulated platelets. However, stimulation of platelets with adenosine
      diphosphate, but not with thrombin, caused a significant increase in cytoplasmic
      Ca2+ concentration during treatment with transdermal E2 plus progesterone. Also
      when stimulating with thrombin, transdermal E2 was more active than oral E2 in
      increasing CD62P expression, a difference that was not reduced by the addition of
      progestogens. In conclusion, hormone replacement therapy only increased Ca2+
      mobilization or CD62P expression in stimulated platelets, and then followed a
      varied pattern that was dependent on the stimulant and on the specific hormonal
      formulation.

PMID- 15166937
TI  - Comparison of plasma D-dimer and thrombus precursor protein in patients with
      operable breast cancer as a potential predictor of lymph node metastasis.
AB  - Fibrin formation and removal is continuous during the development of malignancy.
      Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble
      fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic
      activity. We evaluated the relationship between plasma D-dimer and TpP levels
      with tumor extent and examined the use of these markers as possible predictors of
      lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and
      TpP were measured in these 120 patients (93 breast cancer, 27 benign breast
      disease) and 29 healthy controls. Plasma levels of D-dimer in patients with
      breast cancer were significantly higher than in healthy controls and in those
      with benign breast disease. Plasma D-dimer levels in patients with breast cancer
      were found to be significantly increased according to tumor stage. We also
      observed that plasma levels of D-dimer were higher in patients with lymph node
      metastasis than in patients without metastasis. In contrast, TpP levels were not
      significantly different by the tumor stages and lymph node metastasis. In
      conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing
      fibrinolysis within breast cancer tissue occurs during tumor progression.
      Positive D-dimer levels might be useful for identifying metastatic lymph node in
      patients with operable breast cancer. However, plasma TpP was not found to be a
      sensitive marker for detecting tumor-associated subclinical coagulopathy.

PMID- 15166938
TI  - Prognostic value of a new quantitative D-dimer test in critically ill patients 24
      and 48 h following admission to the intensive care unit.
AB  - A D-dimer assay may predict mortality in medical critically ill patients,
      although no consensus on the clinical utility of this diagnostic test has been
      reached. A prospective single-center study was designed to evaluate whether D
      dimer levels, as measured by a new, rapid assay, correlate with poor outcome in
      critically ill patients. A total of 95 blood samples were collected from medical
      and surgical adult patients 24 and 48 h following admission to the intensive care
      unit (ICU). D-dimer was assayed by the Miniquant quantitative test and correlated
      to the ICU length of stay, the hospital length of stay, the Acute Physiology and
      Chronic Health Evaluation (APACHE) II score and the Simplified Acute Physiology
      Score (SAPS) 24 and 48 h following admission to the ICU, organ system failure
      index and hospital mortality. The 24-h D-dimer level correlated with the 48 h
      APACHE II and SAPS scores (r = 0.41, P = 0.01; and r = 0.39, P = 0.01,
      respectively). The 48-h D-dimer level correlated with the APACHE II and SAPS
      scores at 48 h and with the organ system failure index (number of organ failure)
      (r = 0.54, P = 0.0008; r = 0.60, P = 0.0001; and r = 0.37, P = 0.02,
      respectively). Neither the 24-h nor the 48-h D-dimer levels were predictive of in
      hospital mortality in a multivariate model. We conclude that this simple and new
      laboratory test may serve as an additional tool to predict the clinical severity
      of patients admitted to the ICU.

PMID- 15166939
TI  - Hemostatic gene polymorphisms and the prevalence of thrombotic complications in
      polycythemia vera and essential thrombocythemia.
AB  - Patients with polycythemia vera and essential thrombocythemia are at risk for
      thrombotic and bleeding complications. Currently, no diagnostic test can predict
      thrombohemorrhagic complications. In a prospective study of 86 patients with
      polycythemia vera (43 patients) or essential thrombocythemia (43 patients), we
      examined the possible role of polymorphisms of platelet adhesion receptors
      [glycoprotein (GP) Ibalpha, GPIa, GPIIIa) and clotting factor II (prothrombin's
      G20210A mutation) and clotting factor V (Leiden mutation) in determining the risk
      of thrombotic or bleeding complications. Except for an association between
      vasomotor symptoms and prothrombin mutation (P < 0.001), no significant
      correlation between polymorphism of clotting factors and thrombohemorrhagic
      complications was identified. When the entire patient cohort was considered, the
      polymorphisms of platelet adhesion receptors were not associated with the risk
      for thrombotic or bleeding complications. However, among patients with
      polycythemia vera, the presence of the PlA2 allele of GPIIIa was associated with
      an increased risk of arterial thrombosis. In view of previous studies linking the
      presence of the PlA2 allele of GPIIIa to a higher risk for coronary artery
      thrombosis, our data have physiologic relevance. However, they need to be
      confirmed in a larger study.

PMID- 15166940
TI  - Inhibition of thrombin-induced feedback activation of factor V: a potential
      pathway for inhibition of thrombin generation by melagatran.
AB  - The feedback mechanism by which melagatran, the active form of the oral direct
      thrombin inhibitor ximelagatran, inhibits thrombin generation was investigated in
      vitro, using an endogenous thrombin potential (ETP) assay. Melagatran decreased
      ETP in a concentration-dependent manner and increased the time to thrombin peak.
      FEIBA reversed the melagatran-induced reduction in ETP in a concentration
      dependent manner and marginally reduced the prolongation of the time to thrombin
      peak. Similar results were observed for prothrombin as were seen with FEIBA. Both
      activated factor V and Russell's Viper Venom-factor V activator reversed the
      melagatran-induced prolongation in time to thrombin peak in a concentration
      dependent manner and partially restored ETP. Prothrombin, in combination with
      Russell's Viper Venom-factor V or activated factor V, reversed both the
      melagatran-induced reduction in ETP and the prolongation in time to thrombin
      peak, in a concentration-dependent manner. These results indicate that inhibition
      of thrombin-mediated amplification reactions in blood coagulation is an effective
      way to delay or inhibit thrombin generation.

PMID- 15166941
TI  - Effects of a moderate-intensity aerobic program on blood viscosity, platelet
      aggregation and fibrinolytic balance in young and middle-aged sedentary subjects.
AB  - Regular physical activity is associated with reduced risk of cardiovascular
      disease although the mechanisms are unclear. Recent population-based studies
      suggest that the effect of physical activity may be at least partly a result of
      action on hemostasis. We tested the hypothesis that moderate-intensity aerobic
      training improves fibrinolytic activity and reduces platelet aggregation and
      blood viscosity. In 15 young (11 males and four females; age, 24-32 years) and 15
      middle-aged (11 males and four females; age, 45-65 years) healthy, non-smoker,
      sedentary subjects, the maximum oxygen consumption, adenosine diphosphate-induced
      platelet aggregation, tissue plasminogen activator and plasminogen activator
      inhibitor type 1, antigen, hematocrit and blood viscosity were measured at
      baseline and after 12 weeks of aerobic exercise training (40 min three times a
      week at a training intensity adjusted to 60% of the individual heart rate
      reserve). After training, the maximum oxygen consumption was increased by 9% (P <
      0.01) in the young group and by 7.3% (P < 0.05) in the middle-aged group.
      Adenosine diphosphate-platelet aggregation significantly decreased in the young (
      30%; P < 0.05). The middle-aged group showed a 10.4% decrease in hematocrit (P <
      0.05), and a 11.6 and 16.6% decrease in blood viscosity at 450/s and at 90/s
      rates of shear, respectively (P < 0.05), while the plasminogen activator
      inhibitor type 1 antigen plasma level increased 135% (P < 0.01). These data, some
      not consistent with others, only partially support the hypothesis that the
      beneficial effects of physical activity result from action on hemostatic balance.
      In particular, the changes in the fibrinolytic system in middle-aged subjects
      might suggest increased thrombotic risk. Thus a simple, straightforward
      conclusion is not possible at present, and further studies are required.

PMID- 15166942
TI  - The effect of fibrinogen concentrate administration on coagulation abnormalities
      in a rat sepsis model.
AB  - Disseminated intravascular coagulation is a disorder that affects the function of
      the clotting system and is frequently associated with sepsis or septic shock. One
      of its leading symptoms is the decrease in circulating fibrinogen. We
      investigated the effect of fibrinogen concentrate (Haemocomplettan P) on
      fibrinogen plasma levels, coagulation parameters and mortality in a rat model of
      sepsis-induced disseminated intravascular coagulation. The disseminated
      intravascular coagulation was characterized by elevated thrombin-antithrombin
      complex and a sharp drop in circulating fibrinogen. Coagulation abnormalities
      were evaluated by thrombelastography. Plasma fibrinogen levels decreased from
      2.06 +/- 0.2 to 0.16 +/- 0.1 g/l following administration of bacterial
      lipopolysaccharide. Thrombelastographic measurements revealed a concurrent
      decrease in maximum amplitude and an increase in reaction time. Treatment with
      fibrinogen concentrate (Haemocomplettan P, 25-200 mg/kg body weight
      intravenously) resulted in a statistically significant dose-dependent increase in
      fibrinogen plasma levels and amelioration of the measured coagulation
      abnormalities. Fibrinogen plasma concentrations were restored to normal levels
      when 200 mg/kg body weight fibrinogen concentrate was administered. A significant
      decrease in sepsis-induced mortality was observed in animals treated with
      Haemocomplettan P.

PMID- 15166943
TI  - Venous and arterial thrombosis in rat models: dissociation of the antithrombotic
      effects of glycosaminoglycans.
AB  - Fucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber, made up
      of alternating beta-D-glucuronic acid and N-acetyl-beta-D-galactosamine units,
      like mammalian chondroitin sulfate. But the beta-D-glucuronic acid residues have
      branches of sulfated fucose, which confer high anticoagulant and antithrombotic
      properties on this compound. We have now compared the anticoagulant, bleeding and
      antithrombotic effects of this fucosylated chondroitin sulfate and its carboxyl
      reduced derivative. Both compounds have similar anticoagulant action, mostly due
      to acceleration of thrombin inhibition in the presence of heparin cofactor II.
      The native glycosaminoglycan shows a correlation among anticoagulant, bleeding
      and antithrombotic effects. Inhibition of thrombosis in an arterio-venous shunt
      occurs at low doses, which are almost ineffective in modifying the anticoagulant
      activity of plasma. In a venous experimental model, on the contrary,
      antithrombotic activity requires high doses and occurs concomitantly with an
      increase in the anticoagulant activity of plasma. The action of fucosylated
      chondroitin sulfate on thrombosis is apparently unrelated to its effect on
      platelet aggregation. The carboxyl-reduced derivative of fucosylated chondroitin
      sulfate prevented thrombosis in the arterio-venous shunt, but not in the venous
      experimental model. This derivative did not increase bleeding, in spite of its
      potent anticoagulant activity. Therefore, our results reveal a dissociation of
      the anticoagulant, bleeding and antithrombotic effects of the glycosaminoglycan.
      Furthermore, we demonstrate that a polysaccharide may be a potent inhibitor of
      one type of thrombotic episode, but inactive on another. We propose that the
      different effects of fucosylated chondroitin sulfate and its carboxyl-reduced
      derivative on venous thrombosis may be related to adherence of the
      glycosaminoglycan to the vessel wall.

PMID- 15166944
TI  - Hemodilution with lactated Ringer's solution causes hypocoagulability in rabbits.
AB  - Hemodilution (HD) has been associated with hypercoagulability. It was
      hypothesized that HD with lactated Ringer's solution (LR) would result in
      hypercoagulability in rabbits. Sedated rabbits (n = 12) underwent HD with LR (40%
      estimated blood volume replaced with five volumes of LR) via ear vessels. Key
      procoagulants and anticoagulant activities were assessed prior to and 3 h after
      HD. Hemostatic function was assessed with the activated coagulation time and
      platelet-inhibited thrombelastography. Circulating tissue factor activity was
      much more diluted (-67.2% from baseline) than tissue factor pathway inhibitor (
      45.2%) or antithrombin (-9.5%) activities after HD. HD significantly decreased
      factor VIII complex activity (-31.5%) more than protein C activity (-5.9%), and
      factor X activity (-29.2%) was more diluted than antithrombin activity. The
      activated coagulation time and thrombelastography demonstrated a significant
      decrease in hemostatic function after HD. Hemodilution with LR caused
      hypocoagulability in the rabbit. A greater decrease in circulating procoagulant
      activity than anticoagulant activity appears to be the mechanism underlying HD
      mediated decreases in hemostasis.

PMID- 15166945
TI  - ABO locus O1 allele and risk of myocardial infarction.
AB  - An association between ABO blood group and myocardial infarction (MI) has been
      described. One probable mechanism underlying this association is the influence of
      ABO blood group on plasma von Willebrand factor (vWF) levels. We conducted this
      genetic study to test whether the ABO O1 allele is associated with low vWF plasma
      levels and with a reduced risk of MI. Cases consisted of 793 consecutive,
      angiographically examined patients with either acute or prior MI. As controls
      served 340 angiographically examined patients with neither coronary artery
      disease nor signs of MI. ABO1 locus alleles (A1, A2, B, O1, O2) were identified
      with polymerase chain reaction and fluorogenic probes. The distribution of O1
      alleles in the MI group versus the control group was: no O1 allele (15.4%/10.0%),
      one O1 allele (49.7%/50.0%) and two O1 alleles (34.9%/40.0%) (P = 0.035). O1
      allele carriage was associated with a 39% reduction in the risk of MI unadjusted
      odds ratio, 0.61; 95% confidence interval, 0.41-0.91). The significant
      association was maintained after adjustment for other cardiovascular risk
      factors. vWF antigen levels correlated with the number of O1 alleles (P =
      0.00003) in a separate control group (n = 164). Carriage of the O1 allele is
      associated with a decreased risk of myocardial infarction, with homozygosity
      providing the greatest protection.

PMID- 15166947
TI  - Association of the platelet glycoprotein receptor IIIa (PlA1/PlA1) genotype with
      coronary artery disease in Arabs.
AB  - The PlA2 allele (heterozygotes or homozygotes) resulting from a genetic
      polymorphism in the glycoprotein IIIa gene has been proposed as a potential
      genetic factor linked to platelet hyperaggregability and increased risk of
      coronary artery disease (CAD). Such an association could only be established in
      some ethnic groups. There were no previous reports investigating the distribution
      of this allele and its possible link to CAD in Arabs. We used the polymerase
      chain reaction and allele-specific restriction digestion for determining the
      prevalence of this allele in 509 healthy blood donors (BD) and 451
      angiographically confirmed CAD patients of Arabic ethnic background. For the BD
      group (n = 509), 70.7% were homozygous PlA1/PlA1, 26.9% were heterozygous
      PlA1/PlA2 and 2.4% were homozygous PlA2/PlA2. Within the CAD group (n = 451),
      77.2% were homozygous PlA1/PlA1, 19.5% were heterozygous PlA1/PlA2 and 3.3% were
      homozygous PlA2/PlA2. The PlA1 allele frequency was 0.84 and 0.87, and for the
      PlA2 was 0.16 and 0.13 for the BD and CAD groups, respectively. In conclusion,
      our results suggest that the PlA1/PlA1 genotype (P = 0.029) is associated with
      CAD in Saudi Arabs.

PMID- 15166946
TI  - Activation of fibrinolysis and coagulation in non-occlusive intestinal ischaemia
      in a pig model.
AB  - The present study was carried out to explore the dynamics of the fibrinolytic and
      coagulation systems during non-occlusive intestinal ischaemia in a porcine model.
      Nineteen pigs underwent laparotomy. The inferior mesenteric artery and the
      collateral vessels to the rectum were ligated. The superior mesenteric artery
      (SMA) was isolated at its origin from the aorta, and constriction and flowmeter
      devices were applied. The blood flow of the SMA was reduced to cause ischaemia in
      the distal colon within the pHi interval 6.9-7.1. Fibrinogen, soluble fibrin, D
      dimer, tissue plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1)
      complex and albumin were measured. Corrections for pig D-dimer and albumin were
      performed. Fibrinogen decreased significantly after laparotomy (P < 0.0001) and
      further after constriction of the SMA (P < 0.05), whereas soluble fibrin
      increased significantly (P < 0.005) after constriction of the SMA. The tPA/PAI-1
      complex increased significantly after laparotomy (P < 0.05) and, after
      constriction of the SMA, the values first tended to decrease (P = 0.06) and then
      to increase (P = 0.056). The need to calibrate assays of human plasma proteins
      when applying them to experimental pig models was demonstrated. After
      constriction of the SMA, there was a rapidly reversed peak in the coagulation
      marker soluble fibrin and a strong tendency of alteration of the fibrinolytic
      marker tPA/PAI-1 complex.

PMID- 15166948
TI  - Detection of anticoagulant activities of isolated canine fibrinogen degradation
      products X, Y, D and E using resonance thrombography.
AB  - The objective of the study was to examine the influence of fibrinogen degradation
      products (FDPs) on the resonance thrombogram (RTG). Different concentrations (up
      to 5 g/l plasma) of purified canine FDP X, FDP Y, FDP D and FDP E were added to
      the blood of healthy dogs and the RTG was measured. Of the examined RTG
      parameters [reaction time, fibrin formation time (RTG-f), and fibrin amplitude],
      FDP X, FDP Y, and FDP D showed the clearest effects on RTG-f. RTG-f was on the
      average prolonged by addition of 0.06 g/l FDP Y, 0.15 g/l FDP X, and 0.17 g/l FDP
      D to the upper limit of the reference range. Based on the gram amounts of the
      added FDP, fragment Y also showed in other RTG parameters the most marked effect,
      followed by FDP X and FDP D. FDP E showed no substantial effect rS [Spearmans
      rank correlation coefficient (< 0.3, P > or = 0.5)] in any of the examined RTG
      parameters. The closest correlation between FDP concentration and the result of
      the different RTG parameters was found for the RTG-f (FDP X, rS = 0.819; FDP Y,
      rS = 0.795; FDP D, rS = 0.764). The results indicate that RTG is a useful
      screening test for the detection of increased FDP concentrations.

PMID- 15166949
TI  - PlA polymorphism and platelet reactivity following clopidogrel loading dose in
      patients undergoing coronary stent implantation.
AB  - The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has
      been suggested to play an important role in coronary thrombosis. In vitro studies
      have shown differences for this polymorphism in platelet sensitivity towards
      antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic
      modulation. The aim of the study was to assess the modulatory effect of the PlA
      polymorphism on clopidogrel-induced antiplatelet effects in 38 patients
      undergoing coronary stent implantation receiving a 300 mg clopidogrel loading
      dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin
      expression in platelets stimulated with 2 micromol/l adenosine diphosphate using
      whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and
      heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a
      higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P =
      0.02) during the overall study time course and a lower antiplatelet effect to a
      300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In
      conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity
      towards clopidogrel front loading in patients undergoing coronary stenting. This
      suggests the need for individualized antithrombotic regimens to optimally inhibit
      platelet reactivity.

PMID- 15166950
TI  - Successful treatment of post-exertion acute myocardial infarction by primary
      angioplasty and stenting in a patient with antiphospholipid antibody syndrome.
AB  - Antiphospholipid syndrome is a disorder characterized by arterial and venous
      thromboses, thrombocytopaenia and stroke. Acute myocardial infarction is rarely
      associated with this syndrome. The treatment of these patients is a clinical
      challenge. This report is about a patient with antiphospholipid syndrome
      presenting with an acute myocardial infarction after an exercise test. The
      infarct-related coronary artery was successfully revascularized by primary
      angioplasty and stenting without any major bleeding complications. We think that
      the physical exertion could have favoured acute coronary thrombosis in this
      particular setting.

PMID- 15166951
TI  - A mutation in LMAN1 (ERGIC-53) causing combined factor V and factor VIII
      deficiency is prevalent in Jews originating from the island of Djerba in Tunisia.
AB  - Combined deficiency of factor V and factor VIII is a rare autosomal recessive
      bleeding disorder that is caused by mutations in the LMAN1 or MCFD2 genes. These
      genes encode for proteins that form a complex that takes part in the transport of
      factor V and factor VIII from the endoplasmic reticulum to Golgi. Two mutations
      in LMAN1 have been observed in Jews: a guanine (G) insertion in exon 1 among
      Middle Eastern Jewish families, and a thymidine (T) to cytosine (C) transition in
      intron 9 at a donor splice site among Tunisian families. For each mutation,
      haplotype analysis revealed a founder effect. Because all affected Tunisian
      families belong to an ancient Jewish community in the island of Djerba off the
      coast of Tunisia, we screened members of this community for the intron 9 T --> C
      transition. Among 233 apparently unrelated individuals five heterozygotes were
      detected, predicting an allele frequency of 0.0107 (95% confidence interval,
      0.0035-0.0248), while among 259 North African Jews none was found to carry the
      mutation. The prevalence of the mutation in Djerba Jews is consistent with the
      observation that all affected Tunisian Jewish families have origins in Djerba and
      with the finding of a common haplotype for the 9 + 2 T --> C mutation. The G
      insertion in exon 1 was found in one of 245 Iraqi Jews, predicting an allele
      frequency of 0.0022 (95% confidence interval, 0.0001-0.0123), but in none of 180
      Iranian Jews examined. In view of the relatively low frequency of the mutations
      in the respective populations it seems reasonable to advocate carrier detection
      and prenatal diagnosis only in affected families.

PMID- 15166952
TI  - Thromboelastography with citrated blood: comparability with native blood,
      stability of citrate storage and effect of repeated sampling.
AB  - Thromboelastography (TEG) with recalcified citrate blood is used as an
      alternative to native blood, but there is insufficient data regarding sample
      reliability and stability over time. Thus, TEG parameters of freshly drawn native
      blood were compared with those of recalcified citrated blood without celite in 10
      healthy subjects, and the effect of repeated sampling over 240-min storage was
      evaluated. All TEG parameters following citrate storage remained stable between
      30 min [clot formation time (k) = 7.2 +/- 0.6 min; maximum amplitude (ma) = 48.5
      +/- 1.9 mm] and 2 h (k = 7.1 +/- 0.6 min; ma = 46.2 +/- 2.5 mm) after initial
      sampling, but were not comparable with native blood (k = 9.3 +/- 0.7 min; ma =
      43.5 +/- 2.5 mm) at any time point. TEG parameters of repeatedly sampled citrated
      blood had a significant overall hypercoagulable trend throughout 4 h following
      sampling. In conclusion, in order to achieve reproducible results, citrated blood
      without celite may be utilized between 30 min and 2 h following sampling, but in
      normal subjects the TEG parameters following citrate storage are not comparable
      with native blood, possibly because of incomplete inhibition of the activation of
      the coagulation cascade. Thus, citrated blood can be used as a surrogate of
      native blood in assessing coagulation using TEG, but if repeated sampling is used
      the trend in hypercoagulability must be considered.

PMID- 15166953
TI  - Appropriate timing of cholecystectomy in patients who present with moderate to
      severe gallstone-associated acute pancreatitis with peripancreatic fluid
      collections.
AB  - SUMMARY BACKGROUND DATA: Standard management of gallstone-associated acute
      pancreatitis calls for cholecystectomy to be performed during the same
      hospitalization after acute symptoms have subsided. However, infectious
      complications are common when cholecystectomy is performed sooner than 3 weeks
      after severe acute pancreatitis. Fluid collections, common in patients with
      moderate to severe acute pancreatitis, are additionally problematic. No previous
      study has examined the role of peripancreatic fluid collections and subsequent
      pseudocyst in outcomes after cholecystectomy in these patients. OBJECTIVES: We
      compare results of delaying cholecystectomy after moderate to severe acute
      pancreatitis with early cholecystectomy. METHODS: Since 1987, all patients with
      moderate to severe gallstone-associated acute pancreatitis and associated fluid
      collections were addressed. Moderate to severe acute pancreatitis was defined as
      > 5 Ranson prognostic indicators. Fluid collection was established by computed
      tomography (CT) scan. Patients were evaluated for duration of hospitalization,
      complications of cholecystectomy, resolution or persistence of pseudocysts,
      nonoperative interventions performed on pseudocysts, intercurrent episodes of
      acute pancreatitis during the monitoring period, episodes of sepsis, and
      mortality. RESULTS: A total of 187 patients with moderate to severe gallstone
      associated acute pancreatitis survived their acute stage; 151 had peripancreatic
      fluid collections. Seventy-eight of the 187 had early cholecystectomy, 62 of whom
      had fluid collections; 109 were monitored before cholecystectomy, 89 of whom had
      fluid collections. Fluid collections resolved without intervention in 36 (40%) of
      89 in the monitored group and in 13 (21%) of 62 in the early cholecystectomy
      group. Percutaneous drainage was performed in 16 (18%) of 89 in the monitored
      group and in 31 (50%) of 62 in the early cholecystectomy group. Sepsis occurred
      in 6 (7%) of 89 in the monitored group and 29 (47%) of 62 in the early
      cholecystectomy group. Complications of cholecystectomy occurred in 6 (5.5%) of
      109 of the monitored patients and in 34 (44%) of 78 in the early cholecystectomy
      group. Fifty-three patients in the monitored group and 49 patients in the early
      cholecystectomy group required operative pseudocyst-enterostomy. This procedure
      was combined with cholecystectomy in the monitored patients. Mean hospitalization
      was longer in the early operation group. CONCLUSION: Cholecystectomy should be
      delayed in patients who survive an episode of moderate to severe acute biliary
      pancreatitis and demonstrate peripancreatic fluid collections or pseudocysts
      until the pseudocysts either resolve or persist beyond 6 weeks, at which time
      pseudocyst drainage can safely be combined with cholecystectomy.

PMID- 15166954
TI  - Practicing surgeons lead in quality care, safety, and cost control.
AB  - OBJECTIVE: To report the experiences of 66 surgical specialists from 15 different
      hospitals who performed 43 CPT-based procedures more than 16,000 times. SUMMARY
      BACKGROUND DATA: Surgeons are under increasing pressure to demonstrate patient
      safety data as quantitated by objective and subjective outcomes that meet or
      exceed the standards of benchmark institutions or databases. METHODS: Data from
      66 surgical specialists on 43 CPT-based procedures were accessioned over a 4-year
      period. The hospitals vary from a small 30-bed hospital to large teaching
      hospitals. All reported deaths and complications were verified from hospital and
      office records and compared with benchmarks. RESULTS: Over a 4-year inclusive
      period (1999-2002), 16,028 elective operations were accessioned. There was a
      total 1.4% complication rate and 0.05% death rate. A system has been developed
      for tracking outcomes. A wide range of improvements have been identified. These
      include the following: 1) improved classification of indications for systemic
      prophylactic antibiotic use and reduction in the variety of drugs used, 2)
      shortened length of stay for standard procedures in different surgical
      specialties, 3) adherence to strict indicators for selected operative procedures,
      4) less use of costly diagnostic procedures, 5) decreased use of expensive home
      health services, 6) decreased use of very expensive drugs, 7) identification of
      the unnecessary expense of disposable laparoscopic devices, 8) development of a
      method to compare a one-surgeon hospital with his peers, and 9) development of
      unique protocols for interaction of anesthesia and surgery. The system also
      provides a very good basis for confirmation of patient safety and improvement
      therein. CONCLUSIONS: Since 1998, Quality Surgical Solutions, PLLC, has developed
      simple physician-authored protocols for delivering high-quality and cost
      effective surgery that measure up to benchmark institutions. We have discovered
      wide areas for improvements in surgery by adherence to simple protocols,
      minimizing death and complications and clarifying cost issues.

PMID- 15166955
TI  - Inflammatory mechanisms contributing to pancreatic cancer development.
AB  - OBJECTIVE: Pancreatic cancer is the most deadly of all gastrointestinal (GI)
      malignancies, yet relatively little is known regarding mechanisms of tumor
      development including the role of inflammation. SUMMARY BACKGROUND DATA: Chronic
      pancreatitis (CP) increases the risk of developing cancer by 10- to 20-fold;
      mediators of the chronic inflammatory process and the surrounding fibrotic stroma
      likely support a transformation to malignancy, yet the exact mechanisms remain
      undefined. The purpose of our present study was to determine potential
      inflammatory components in epithelial and stromal cells that may contribute to
      both CP and pancreatic cancers. METHODS: Specimens of normal pancreas, CP, and
      pancreatic cancer were examined using laser-capture microdissection (LCM), gene
      array, and immunohistochemistry. RESULTS: Gene array analysis from LCM-dissected
      tissues demonstrated: (i) increased expression of interleukin-8 (IL-8), an
      activator of the inflammatory factor nuclear factor-kappaB (NF-kappaB), and (ii)
      decreased expression of IkappaB (an inhibitor of NF-kappaB) in CP ductal cells
      compared with normal ducts. Compared with CP, cancers demonstrated: (i) increased
      expression of tumor related genes including S100A4, cyclin E1, and epidermal
      growth factor (EGF) receptor, and (ii) expression of matrix metalloproteinase 2,
      a pro-invasive factor for tumor cells, which was not present in the CP stroma.
      Increased staining of both the p50 NF-kappaB subunit and IKKalpha kinase (a
      protein that allows activation of NF-kappaB) was noted in CP and cancers.
      CONCLUSIONS: Our results demonstrate that similar inflammatory components and
      downstream effectors are present in CP and pancreatic cancers. Importantly, these
      findings suggest that a common pathway for pancreatic cancer development may be
      through a chronic inflammatory process including stroma formation. These findings
      may lead to novel strategies for pancreatic cancer prophylaxis based on
      inhibition of inflammatory mediators.

PMID- 15166956
TI  - Health Insurance Portability Accountability Act (HIPAA) regulations: effect on
      medical record research.
AB  - OBJECTIVE: To evaluate the effect of impending HIPAA regulations on Applications
      for Exemptions from Institutional Review Board (IRB) approval. SUMMARY BACKGROUND
      DATA: HIPAA was implemented to reduce potential for misuse of personal
      information and restricts access to medical records by insurers, employers, and
      clinical researchers. We hypothesized that HIPAA regulations adversely impact
      medical records research. METHODS: The UW-Madison Human Subjects Committee
      database was accessed to evaluate success and delays in processing Applications
      for Exemption between September 1999 and March 2003. The number of protocols
      submitted, number of required revisions, and number considered nonexempt
      (requiring full IRB review) were determined. RESULTS: Prior to 2000, applications
      for medical records research were rare (11 applications in 1999-2000). In
      anticipation of the implementation of HIPAA regulations, a new application
      process was instituted in 2001. During that year, 92 of 103 were approved by an
      expedited process with few requiring full IRB approval. In 2002 to 2003,
      submissions increased to 199 and approval without revision dropped to 59% (P <
      0.0001) as the number requiring revision (25%) and full IRB approval (16%)
      increased significantly (P < 0.0001 and P < 0.05, respectively). Of the 31
      requiring full IRB approval, 7 were pursued while 24 (77%) were abandoned.
      CONCLUSION: HIPAA appears to inhibit medical record and database research.
      Ethical considerations in healthcare research are paramount, but current HIPAA
      implementation strategies increase workload for HSC and researchers, and increase
      the dropout rate for proposed studies when investigators are unable or unwilling
      to meet the regulatory requirements. It is unclear whether or to what degree the
      new requirements add to protection of privacy. Studies designed to investigate
      the costs and effects on quantity and/or quality of research should be
      prospectively implemented.

PMID- 15166957
TI  - Laparoscopic esophagomyotomy for achalasia: does anterior hemifundoplication
      affect clinical outcome?
AB  - OBJECTIVE: To determine whether the addition of anterior hemifundoplication to
      laparoscopic esophagomyotomy for achalasia yields better clinical outcomes than
      laparoscopic esophagomyotomy alone. SUMMARY BACKGROUND DATA: Although
      hemifundoplication may prevent gastroesophageal reflux after esophagomyotomy for
      achalasia, it may also lead to persistent dysphagia in these patients with
      esophageal aperistalsis. METHODS: This is a retrospective study of 51 consecutive
      patients (mean age 47.5 +/- 12.6 years) who had laparoscopic esophagomyotomy for
      achalasia by our group between August 1995 and January 2001. In 29 patients (57%)
      an anterior hemifundoplication was added to the esophagomyotomy. In 22 patients
      (43%), no wrap was added. Patients scored (0 = none; 1 = mild; 2 = moderate; 3 =
      severe) symptom severity (dysphagia, regurgitation, heartburn, chest pain)
      preoperatively and postoperatively. Weight gain, use of gastrointestinal (GI)
      medication, tolerance to food, and patient satisfaction were also assessed.
      RESULTS: Mean patient follow-up was 33 months, and there were no operative
      deaths. Four patients were converted to open operation (8%). The wrap and no wrap
      groups were similar in terms of esophageal dilation, preoperative symptom
      severity and duration (5.7 +/- 7.1 versus 6.1 +/- 7.0 years), and preoperative
      weight loss (18 +/- 15 versus 20 +/- 20 pounds). Both groups had similar
      improvement in symptom grade postoperatively and equivalent satisfaction rates
      (86%). Postoperative weight gain, GI medication use, and food intolerance was
      also similar. Postoperatively, patients in the wrap group did not have higher
      dysphagia scores or lower heartburn scores than the no wrap group. CONCLUSION:
      The addition of anterior hemifundoplication to esophagomyotomy for achalasia does
      not improve or worsen clinical results.

PMID- 15166958
TI  - Intraductal papillary mucinous neoplasms of the pancreas: an updated experience.
AB  - OBJECTIVE: To update the authors' experience with intraductal papillary mucinous
      neoplasms (IPMNs) of the pancreas. BACKGROUND DATA: IPMNs are intraductal mucin
      producing cystic neoplasms of the pancreas with clear malignant potential. Since
      the authors' 2001 report, the number of IPMNs resected at our institution has
      more than doubled, providing an opportunity to define the clinical features of
      this distinct neoplasm. METHODS: All patients undergoing pancreatic resection for
      an IPMN at the Johns Hopkins Hospital between January 1987 and March 2003 were
      evaluated. Noninvasive IPMNs were classified as "adenoma," "borderline," or
      "carcinoma-in situ" (CIS) depending on the degree of dysplasia within the
      specimen. Invasive cancers were classified as tubular, colloid, mixed, or
      anaplastic types. Pathology was retrospectively reviewed to identify main-duct or
      branch-duct origin of the tumors. Long-term overall survival for patients having
      IPMNs with invasive cancer was compared with those patients having IPMNs without
      an invasive component. RESULTS: Between January 1987 and March 2003, inclusive,
      136 pancreatic resections were performed for patients with IPMNs, with 78
      resections performed since January 2001. The mean age of the patients was 66.8 +/
      1.1 years, with 57% being male and 89% white. Pancreaticoduodenectomy was
      performed in 71% of patients, total pancreatectomy in 15%, distal pancreatectomy
      in 12%, and central pancreatic resection in 2%. IPMNs without evidence of
      invasive cancer were identified in 62% (n = 84) of patients (17% adenoma, 28%
      borderline, or 55% CIS). The remaining 38% (n = 52) of patients had IPMNs with
      associated invasive cancer (60% tubular, 27% colloid, 7% mixed, and 6%
      anaplastic). The mean age of patients with IPMN adenoma was 63.2 years, 66.7
      years for those with borderline/CIS IPMNs, and 68.1 years for those with invasive
      cancer (P = 0.08, adenomas vs. invasive cancer). In those patients with invasive
      cancers, 15% had invasive cancer at the final surgical margin, 23% had IPMN
      without invasive cancer at the margin, and 54% had lymph node metastases.
      Residual IPMN was identified at the neck or uncinate margin in 24% of patients
      with noninvasive IPMNs. The overall 5-year survival for patients having IPMNs
      without invasive cancer was 77% (several deaths secondary to metachronous
      invasive cancer), compared with 43% in those patients with an invasive component
      (P < 0.0001). There were no differences in survival when comparing adenomas,
      borderline neoplasms, and CIS. Similarly, there were no statistically significant
      differences in survival when comparing branch-duct, main-duct, and combined
      variants; however, the branch-duct variants were more often noninvasive. For
      those patients with invasive IPMNs, 2-year survival was 40% when margins were
      positive for invasive cancer or for IPMN without invasive cancer, and 60% when
      margins were tumor-free (P = 0.15). Those patients with colloid carcinomas (n =
      14) had improved survival compared with those with tubular carcinomas (n = 31),
      with 5-year survival rates of 83% and 24%, respectively. IPMN recurrences and
      deaths from cancer occurred in patients with both invasive and noninvasive IPMNs
      at initial resection. CONCLUSIONS: IPMNs continue to be recognized with
      increasing frequency. Five-year survival for those patients following resection
      of IPMNs with invasive cancer (43%) is improved compared with those patients with
      resected pancreatic ductal adenocarcinoma in the absence of IPMN (averages 15%
      25%). Survival following resection of IPMNs without invasive cancer (regardless
      of degree of dyplasia) is good, but recurrent disease in the residual pancreas
      suggests that long-term surveillance is critical. Based on the age at resection
      data, there appears to be a 5-year lag time from IPMN adenoma (63.2 years) to
      invasive cancer (68.1 years).

PMID- 15166959
TI  - Endoleak following endovascular abdominal aortic aneurysm repair: implications
      for duration of screening.
AB  - OBJECTIVE: Endovascular abdominal aortic aneurysm repair (EAR) requires long-term
      surveillance for endoleak or increase in aneurysm diameter. We analyzed the
      natural history of and risk factors for endoleak development. SUMMARY BACKGROUND
      DATA: Endoleak is a common complication of EAR that can lead to aneurysm
      enlargement and even rupture. Following EAR, imaging studies are used to identify
      leaks since patients with endoleak may require additional endovascular
      interventions or conversion to open repair. No criteria currently exist for
      cessation or reduction in frequency of screening imaging studies. METHODS: Data
      on 220 patients undergoing EAR were retrospectively reviewed. Kaplan-Meier
      survival analysis and Cox proportional hazards regression were used with the end
      point being new endoleak development. Potential risk factors included
      preoperative aneurysm diameter, number of negative surveillance studies, and
      postoperative increase in diameter. RESULTS: A total of 52 patients (24%) who
      underwent EAR had endoleak detected during postoperative follow-up, which
      averaged 19 months (range, 0.4-101 months). One, 6-, 12-, and 24- month endoleak
      free survival was 90%, 80%, 77%, and 73%, respectively. Three leaks occurred
      after year 2, at postoperative months 24, 48, and 85. Increasing number of
      negative screening studies was negatively associated with risk for endoleak
      development (B = -3.122, P < 0.001), while increase in aneurysm diameter was
      positively associated with risk for endoleak (B = 0.072, P = 0.04). CONCLUSION:
      Risk for endoleak declines as the number of negative postoperative scans
      increases, but new endoleaks are identified as late as 7 years following EAR.
      Reduction in screening frequency cannot be uniformly recommended at this time.
      Patients with documented aneurysm expansion should be monitored carefully and
      endoleak should be suspected.

PMID- 15166960
TI  - Jacob: the other Flexner.

PMID- 15166961
TI  - Recurrence and outcomes following hepatic resection, radiofrequency ablation, and
      combined resection/ablation for colorectal liver metastases.
AB  - OBJECTIVE: To examine recurrence and survival rates for patients treated with
      hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only
      for colorectal liver metastases. SUMMARY BACKGROUND DATA: Thermal destruction
      techniques, particularly RFA, have been rapidly accepted into surgical practice
      in the last 5 years. Long-term survival data following treatment of colorectal
      liver metastasis using RFA with or without hepatic resection are lacking.
      METHODS: Data from 358 consecutive patients with colorectal liver metastases
      treated for cure with hepatic resection +/- RFA and 70 patients found at
      laparotomy to have liver-only disease but not to be candidates for potentially
      curative treatment were compared (1992-2002). RESULTS: Of 418 patients treated,
      190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%),
      and 70 laparotomy with biopsy only or arterial infusion pump placement
      ("chemotherapy only," 17%). RFA was used in operative candidates who could not
      undergo complete resection of disease. Overall recurrence was most common after
      RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only
      recurrence after RFA was fourfold the rate after resection (44% vs. 11% of
      patients, P < 0.001), and true local recurrence was most common after RFA (9% of
      patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall
      survival rate was highest after resection (58% at 5 years); 4-year survival after
      resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P <
      0.0001). Survival for "unresectable" patients treated with RFA + resection or RFA
      only was greater than chemotherapy only (P = 0.0017). CONCLUSIONS: Hepatic
      resection is the treatment of choice for colorectal liver metastases. RFA alone
      or in combination with resection for unresectable patients does not provide
      survival comparable to resection, and provides survival only slightly superior to
      nonsurgical treatment.

PMID- 15166962
TI  - Molecular detection of micrometastatic breast cancer in histopathology-negative
      axillary lymph nodes correlates with traditional predictors of prognosis: an
      interim analysis of a prospective multi-institutional cohort study.
AB  - OBJECTIVE: We sought to establish the clinical relevance of micrometastatic
      disease detected by reverse transcription polymerase chain reaction (RT-PCR) in
      axillary lymph nodes (ALN) of breast cancer patients. BACKGROUND: The presence of
      ALN metastases remains one of the most valuable prognostic indicators in women
      with breast cancer. However, the clinical relevance of molecular detection of
      micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN
      has not been established. METHODS: Four hundred eighty-nine patients with T1-T3
      primary breast cancers were analyzed in a prospective, multi-institutional cohort
      study. ALN were analyzed by standard histopathology (H&E staining) and by
      multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP)
      designed to detect breast cancer micrometastases. RESULTS: A positive marker
      signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and
      in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with
      pathology-negative ALN, a positive marker signal was significantly associated
      with traditional indicators of prognosis, such as histologic grade (P = 0.0255)
      and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative
      marker in the panel. CONCLUSION: This is the first report to show that
      overexpression of breast cancer-associated genes in breast cancer subjects with
      pathology-negative ALN correlates with traditional indicators of disease
      prognosis. These interim results provide strong evidence that molecular markers
      could serve as valid surrogates for the detection of occult micrometastases in
      ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this
      patient cohort will help to define the clinical relevance of micrometastatic
      disease in this patient population.

PMID- 15166963
TI  - Intraoperative subareolar radioisotope injection for immediate sentinel lymph
      node biopsy.
AB  - OBJECTIVE: To determine the identification of sentinel lymph node biopsy (SLNB)
      in breast cancer patients after intraoperative injection of unfiltered technetium
      99m sulfur colloid (Tc-99) and blue dye. BACKGROUND: SLNB guided by a combination
      of radioisotope and blue dye injection yields the best identification rates in
      breast cancer patients. Radioisotope is given preoperatively, without local
      anesthesia, whereas blue dye is given intraoperatively. We hypothesized that,
      because of the rapid drainage noted with the subareolar injection technique of
      radioisotope, intraoperative injection would be feasible and less painful for SLN
      localization in breast cancer patients. METHODS: Intraoperative injection of Tc
      99 and confirmation blue dye was performed using the subareolar technique for
      SLNB in patients with operable breast cancer. The time lapse between injection
      and axillary incision, the background count, the preincision and ex vivo counts
      of the hot nodes, and the axillary bed counts were documented. The identification
      rate was recorded. RESULTS: Ninety-six SLNB procedures were done in 88 patients
      with breast cancer employing intraoperative subareolar injection technique for
      both radioisotope (all 96 procedures) and blue dye (93 procedures) injections.
      Ninety-three (97%) procedures had successful identification; all SLNs were hot;
      91 (of 93 procedures with blue dye) were blue and hot. The mean time from
      radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean
      highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with
      failure of localization had previous excisional biopsies: 1 circumareolar and 2
      upper outer quadrant incisions that may have disrupted the lymphatic flow.
      CONCLUSION: Intraoperative subareolar injection of radioisotope rapidly drains to
      the SLNs and allows immediate staging of the axilla, avoiding the need to
      coordinate diagnostic services and a painful preoperative procedure.

PMID- 15166964
TI  - Laryngopharyngeal reflux symptoms better predict the presence of esophageal
      adenocarcinoma than typical gastroesophageal reflux symptoms.
AB  - OBJECTIVE: To determine whether the presence of laryngopharyngeal reflux symptoms
      is associated with the presence of esophageal adenocarcinoma (EAC). BACKGROUND:
      Most patients diagnosed with EAC have incurable disease at the time of detection.
      The majority of these patients are unaware of the presence of Barrett's esophagus
      prior to cancer diagnosis and many do not report typical symptoms of
      gastroesophageal reflux disease (GERD). This suggests that the current GERD
      symptom-based screening paradigm may be inadequate. Data support a causal
      relation between complicated GERD and laryngopharyngeal reflux symptoms. We
      theorize that laryngopharyngeal reflux symptoms are not recognized expeditiously,
      resulting in chronic esophageal injury and an unrecognized progression of
      Barrett's esophagus to EAC. METHODS: This is a case-comparison (control) study.
      Cases were patients diagnosed with EAC (n = 63) between 1997 and 2002. Three
      comparison groups were selected: 1) Barrett's esophagus patients without
      dysplasia (n = 50), 2) GERD patients without Barrett's esophagus (n = 50), and 3)
      patients with no history of GERD symptoms or antisecretory medication use (n =
      56). The risk factors evaluated included demographics, medical history, lifestyle
      variables, and laryngopharyngeal reflux symptoms. Typical GERD symptoms and
      antisecretory medication use were recorded. Multivariate analysis of
      demographics, comorbid risk factors, and symptoms was performed with logistic
      regression to provide odds ratios for the probability of EAC diagnosis. RESULTS:
      The prevalence of patients with laryngopharyngeal reflux symptoms was
      significantly greater in the cases than comparison groups (P = 0.0005). The
      prevalence of laryngopharyngeal reflux symptoms increased as disease severity
      progressed from the non-GERD comparison group (19.6%) to GERD (26%), Barrett's
      esophagus (40%), and EAC patients (54%). Symptoms of GERD were less prevalent in
      cases (43%) when compared with Barrett's esophagus (66%) and GERD (86%) control
      groups (P < 0.001). Twenty-seven percent (17 of 63) of EAC patients never had
      GERD or laryngopharyngeal reflux symptoms. Fifty-seven percent of EAC patients
      presented without ever having typical GERD symptoms. Chronic cough, diabetes, and
      age emerged as independent risk factors for the development of EAC. CONCLUSIONS:
      Symptoms of laryngopharyngeal reflux are more prevalent in patients with EAC than
      typical GERD symptoms and may represent the only sign of disease. Chronic cough
      is an independent risk factor associated with the presence of EAC. Addition of
      laryngopharyngeal reflux symptoms to the current Barrett's screening guidelines
      is warranted.

PMID- 15166965
TI  - Micrometastasis in the sentinel lymph node of breast cancer does not mandate
      completion axillary dissection.
AB  - OBJECTIVE: To determine if micrometastatic disease in the sentinel lymph node is
      a predictor of non-sentinel lymph node (non-SLN) involvement in breast cancer.
      SUMMARY BACKGROUND DATA: Sentinel lymph node biopsy (SLN) is an accepted
      alternative to axillary dissection in staging breast cancer. If the SLN contains
      metastatic foci, the standard recommendation is completion axillary node
      dissection (CAD). However, a large subset of patients with metastasis limited to
      the SLN is unnecessarily subjected to the morbidity of CAD. METHODS: A
      retrospective review of prospectively gathered breast cancer patients having SLN
      was conducted. Patients with metastasis to the SLN were selected for analysis.
      Various clinicopathologic features were analyzed for association with metastasis
      to the non-SLN. RESULTS: A total of 194 women underwent successful SLN
      dissection. Metastasis to the SLN was found in 48 patients (21 had
      micrometastases, 27 had macrometastases). Of those with micrometastases, 16
      underwent CAD with 1 patient having metastasis to the non-SLN. In patients with
      macrometastases, 26 had CAD with 14 patients having non-SLN metastasis.
      Multivariable logistic regression identified only macrometastatic disease in the
      SLN as significantly associated with involvement of the non-SLN (P = 0.03). None
      of the patients with micrometastases, including those without CAD, has evidence
      of local recurrence to date (3-30 months). CONCLUSION: This study demonstrates
      that the incidence of non-SLN involvement is low in SLN that contains only
      micrometastatic foci and is within the accepted range of the false-negative rate
      of SLN. This suggests that a CAD may be omitted in patients with micrometastatic
      disease.

PMID- 15166966
TI  - Vascular endothelium growth factor, surgical delay, and skin flap survival.
AB  - OBJECTIVE: Cytokines may be a mechanism by which surgical delay can increase flap
      survival. We previously found that preoperative vascular endothelium growth
      factor (VEGF) administration in the rat transverse rectus abdominis myocutaneous
      (TRAM) flap could improve skin paddle survival. In this study, we used partial
      elevation of the rat TRAM flap as a surgical delay to assess endogenous cytokine
      expression and tissue survival comparable to undelayed TRAM flaps. METHODS: In
      Part I, TRAM flaps underwent surgical delay procedures; 7 days later, the flaps
      were completely elevated and reinset. At the same time, other flaps were raised
      and reinset without delay. Skin paddle survival in both groups was evaluated at 7
      days. In Part II, skin biopsies from TRAM zones I to IV were taken at the time of
      delay and at intervals of 12, 24, 48, and 72 hours. Specimens were assessed for
      selected cytokine gene expression by reverse transcription-polymerase chain
      reaction analysis (TR-PCR). RESULTS: Surgical delay significantly (P < 0.001)
      increased skin paddle survival in the delayed TRAM flaps (16.14 +/- 1.53 cm,
      81.9%) compared with undelayed flaps (7.68 +/- 3.16 cm, 40.9%). TGF-beta and PDGF
      expressions were not changed by surgical delay, but basic fibroblast growth
      factor (bFGF) and VEGF expressions increased significantly (P < 0.05 and P <
      0.01) after delay. CONCLUSIONS: In the rat TRAM model, surgical delay resulted in
      increased VEGF expression and increased skin paddle survival. These results
      correlate with previous studies showing the preoperative injection of VEGF
      increases skin paddle survival. VEGF may be an important element in the delay
      phenomenon and may be an agent for pharmacological delay.

PMID- 15166967
TI  - The natural history of pancreatitis-induced splenic vein thrombosis.
AB  - OBJECTIVE: To determine the natural history of pancreatitis-induced splenic vein
      thrombosis with particular attention to the risk of gastric variceal hemorrhage.
      SUMMARY BACKGROUND DATA: Previous studies have suggested that splenic vein
      thrombosis results in a high likelihood of gastric variceal bleeding and that
      splenectomy should be performed to prevent hemorrhage. Recent improvements in
      cross-sectional imaging have led to the identification of splenic vein thrombosis
      in patients with minimal symptoms. Our clinical experience suggested that gastric
      variceal bleeding in these patients was uncommon. METHODS: A computerized index
      search from 1993 to 2002 for the medical records of patients with a diagnosis of
      pancreatitis was performed. Fifty-three patients with a diagnosis of pancreatitis
      and splenic vein thrombosis were identified. The medical records of these
      patients were reviewed, and follow-up was completed, including the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC-QLQ). RESULTS: Gastrosplenic varices were identified in 41 patients (77%)
      with varices evident on computed tomography (CT) in 40 of 53 patients, on
      esophagogastroduodenoscopy (EGD) in 11 of 36 patients, and on both CT and EGD in
      10 of 36 patients. This risk of variceal bleeding was 5% for patients with CT
      identified varices and 18% for EGD-identified varices. Overall, only 2 patients
      (4%) had gastric variceal bleeding and required splenectomy. Functional quality
      of life was better than historical controls surgically treated for chronic
      pancreatitis. CONCLUSION: Gastric variceal bleeding from pancreatitis-induced
      splenic vein thrombosis occurs in only 4% of patients; therefore, routine
      splenectomy is not recommended.

PMID- 15166968
TI  - TIPS versus peritoneovenous shunt in the treatment of medically intractable
      ascites: a prospective randomized trial.
AB  - OBJECTIVE: We undertook a prospective randomized clinical trial comparing TIPS to
      peritoneovenous (PV) shunts in the treatment of medically intractable ascites to
      establish relative efficacy and morbidity, and thereby superiority, between these
      shunts. METHODS: Thirty-two patients were prospectively randomized to undergo
      TIPS or peritoneovenous (Denver) shunts. All patients had failed medical therapy.
      RESULTS: After TIPS versus peritoneovenous shunts, median (mean +/- SD) duration
      of shunt patency was similar: 4.4 months (6 +/- 6.6 months) versus 4.0 months (5
      +/- 4.6 months). Assisted shunt patency was longer after TIPS: 31.1 months (41 +/
      25.9 months) versus 13.1 months (19 +/- 17.3 months) (P < 0.01, Wilcoxon test).
      Ultimately, after TIPS 19% of patients had irreversible shunt occlusion versus
      38% of patients after peritoneovenous shunts. Survival after TIPS was 28.7 months
      (41 +/- 28.7 months) versus 16.1 months (28 +/- 29.7 months) after
      peritoneovenous shunts. Control of ascites was achieved sooner after
      peritoneovenous shunts than after TIPS (73% vs. 46% after 1 month), but longer
      term efficacy favored TIPS (eg, 85% vs. 40% at 3 years). CONCLUSION: TIPS and
      peritoneovenous shunts treat medically intractable ascites. Absence of ascites
      after either is uncommon. PV shunts control ascites sooner, although TIPS
      provides better long-term efficacy. After either shunt, numerous interventions
      are required to assist patency. Assisted shunt patency is better after TIPS.
      Treating medically refractory ascites with TIPS risks early shunt-related
      mortality for prospects of longer survival with ascites control. This study
      promotes the application of TIPS for medically intractable ascites if patients
      undergoing TIPS have prospects beyond short-term survival.

PMID- 15166969
TI  - Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal
      metastases.
AB  - OBJECTIVE: To determine the effects of hypoxia-induced ribonucleotide reductase
      (RR) production on herpes oncolytic viral therapy. SUMMARY BACKGROUND DATA:
      Hypoxia is a common tumor condition correlated with therapeutic resistance and
      metastases. Attenuated viruses offer a unique cancer treatment by specifically
      infecting and lysing tumor cells. G207 is an oncolytic herpes virus deficient in
      RR, a rate-limiting enzyme for viral replication. METHODS: A multimerized hypoxia
      responsive enhancer was constructed (10xHRE) and functionally tested by
      luciferase assay. 10xHRE was cloned upstream of UL39, the gene encoding the large
      subunit of RR (10xHRE-UL39). CT26 murine colorectal cancer cells were transfected
      with 10xHRE-UL39, incubated in hypoxia (1% O2) or normoxia (21% O2), and infected
      with G207 for cytotoxicity assays. CT26 liver metastases, with or without 10xHRE
      UL39, were created in syngeneic Balb/C mice (n = 40). Livers were treated with
      G207 or saline. Tumors were assessed and stained immunohistochemically for G207.
      RESULTS: 10xHRE increased luciferase expression 33-fold in hypoxia versus
      controls (P < 0.001). In normoxia, 10xHRE-UL39 transfection did not improve G207
      cytotoxicity. In hypoxia, G207 cytotoxicity increased 87% with 10xHRE-UL39
      transfection versus nontransfected cells (P < 0.001). CT26 were resistant to G207
      alone. Combining 10xHRE-UL39 with G207 resulted in a 66% decrease in tumor
      weights (P < 0.0001) and a 65% reduction in tumor nodules (P < 0.0001) versus
      G207 monotherapy. 10xHRE-UL39-transfected tumors demonstrated greater viral
      staining. CONCLUSIONS: Hypoxia-driven RR production significantly enhances viral
      cytotoxicity in vitro and reduces tumor burden in vivo. G207 combined with RR
      under hypoxic control is a promising treatment for colorectal cancer, which would
      otherwise be resistant to oncolytic herpes virus alone.

PMID- 15166971
TI  - Relationship between loss of pedal sensibility, balance, and falls in patients
      with peripheral neuropathy.
AB  - : The purpose of this study was to describe the relationship between balance and
      foot sensibility in a population of patients with impaired lower extremity
      sensation. The hypothesis was that increasing impairment of sensation correlates
      with impaired balance. To date, no report has investigated the relationship
      between loss of balance with the degree of sensibility in the foot in a
      population with neuropathy. Ten control subjects and 35 patients with sensory
      abnormalities and balance problems related to a neuropathy were evaluated. The
      MatScan Measurement System was used to measure their ability to stand still,
      maintaining their balance with their eyes open and then with their eyes shut. The
      degree to which the person moves while attempting to stand still is defined as
      "sway," which was recorded for normal and neuropathy patients. Sensibility of the
      foot was measured with the Pressure-Specified Sensory Device, which is
      noninvasive and nonpainful. The 1- and 2-point static touch thresholds are
      measured for the pulp of the big toe, medial heel, and the dorsum of the foot.
      Loss of 2- or 1-point sensation was recorded as sensibility score and compared
      with controls. Statistical analysis of data and their comparisons for the 2
      groups was completed. There were 55% females in control and 64% in neuropathy
      patients, whereas average age was 50 and 62 years, respectively. Neuropathy was
      the result of diabetes in 64.5%, hypothyroidism in 19.3%, their combination in
      13%, and of unknown etiology in the remaining 19% of patients. Controls had
      significantly lower mean sway than neuropathy patients (22.9 +/- 9% vs. 189.5 +/-
      180%, P = 0.006). Likewise, sensibility score for normal and neuropathy patients
      was also significantly different (31.4 +/- 9% vs. 232.8 +/- 59%, P <0.0001). When
      compared with the controls, 99% upper limit of confidence, sensibility in the
      neuropathy group at the hallux pulp was abnormal at a level consistent with
      axonal loss in 52% and was completely absent in the remaining 48%. Similarly, at
      the heel, sensibility was normal in 6.5%, abnormal at a level consistent with
      axonal loss in 71%, and absent in the remaining 22.5%. The correlation
      coefficient between sway and sensibility score was 0.36. The results of this
      investigation for the first time document the intuitive relationship between
      increasing loss of foot sensibility and increasing loss of balance. These
      measurements can now be used prospectively to evaluate whether restoration of
      sensation to patients with neuropathy, through peripheral nerve decompression,
      can improve balance and reduce falls/fractures in this patient population.

PMID- 15166970
TI  - Long-term results with resection of radiation-induced soft tissue sarcomas.
AB  - INTRODUCTION: Radiation therapy is increasingly used as adjuvant treatment of
      many childhood and adult malignancies. Radiation-induced sarcoma is a well
      recognized if uncommon event. The objective of this study is to determine the
      prevalence and long-term outcome for patients who develop radiation-induced
      sarcomas. METHODS: From July 1982 to December 2001, 4884 adult patients with
      sarcoma were admitted and treated at our institution and recorded in a
      prospective database. There were 123 (2.5%) patients who had radiation-induced
      soft tissue sarcomas. Survival was determined by Kaplan-Meier analysis. Patient,
      tumor, and treatment characteristics were tested for their prognostic
      significance by log rank and the Cox proportional hazards model. RESULTS: The
      median interval between radiation and development of sarcoma was 103 (6 to 534)
      months. In 114 patients with radiation-induced sarcoma who underwent curative
      resection, the 5-year actuarial survival was 41%, with a median survival of 48
      months at a median follow-up of 36 months for survivors. The most common
      malignancy for which radiation was used was breast cancer (29%), followed by
      lymphoma (16%) and prostate cancer (15%). Malignant fibrous histiocytoma (23%)
      was the most common histologic diagnosis, followed by fibrosarcoma (15%) and
      angiosarcoma (15%). High-grade tumors (n = 85; 79%), age > 60 years (n = 61;
      50%), and gross positive resection margin (n = 36; 32%) were predictive of poor
      sarcoma-specific survival on univariate and multivariate analysis. CONCLUSIONS:
      The increasing utilization of adjuvant radiation therapy, especially for early
      stage breast cancer mandates long-term follow-up to detect radiation-induced
      sarcoma. Surgical resection remains the primary therapy, but 5-year survival
      remains approximately 40%.

PMID- 15166973
TI  - Use of liposuction for secondary revision of irradiated and nonirradiated free
      flaps.
AB  - A number of patients with free tissue transfer require secondary revision to
      improve contour and regional definition to maximize function or appearance.
      However, there is controversy with regard to whether irradiated free flaps can be
      revised safely using liposuction. The purpose of this study was to compare the
      outcomes of revisionary procedures requiring liposuction in irradiated versus
      nonirradiated flaps. From December 1992 to July 2001, office and hospital records
      were reviewed retrospectively to identify patients who had undergone free tissue
      transfer and subsequent flap revision at a single institution. The number of
      revisions, amount of fat aspirated, timing of revision and the postoperative
      complications including infection, hematoma, wound dehiscence, and flap loss were
      reviewed. A total of 41 flap revisions using liposuction alone or with direct
      excision were performed on 33 free flaps (31 head and neck, 1 chest wall, and 1
      extremity). The rectus musculocutaneous flap was the most commonly revised (88%).
      The average length of time to secondary revision of patients who had received
      postoperative radiotherapy to their flaps was significantly higher that those
      whose flaps had not been irradiated (P < 0.05). There were no postoperative
      complications except for 1 partial (20%) flap loss in a patient whose flap was
      irradiated. The difference in complication rates between the irradiated and
      nonirradiated group was not statistically significant. Secondary free flap
      revision using liposuction and direct excision is a safe technique for
      recontouring free flaps. There was no significant difference in complication
      rates for irradiated and nonirradiated flaps. Postoperative radiation therapy is
      therefore not a contraindication to secondary revision. However, these procedures
      should be delayed for several months after the acute effects of radiation have
      resolved.

PMID- 15166975
TI  - Incidence of nonlocalization of sentinel lymph nodes using preoperative
      lymphoscintigraphy in 74 consecutive head and neck melanoma and Merkel cell
      carcinoma patients.
AB  - INTRODUCTION: Lymphatic drainage pathways in the head and neck region are more
      variable than in any other location of the body. Occasionally, head and neck
      lymphoscintograms fail to identify a definitive lymphatic drainage pattern,
      making preoperative and intraoperative identification of sentinel nodes very
      difficult. The purpose of this study was to determine the incidence of
      nonlocalization on lymphoscintigraphy of sentinel nodes in patients with head and
      neck cutaneous malignancies. METHODS: A retrospective chart review was conducted
      of a single surgeon's (WKS) 135 consecutive head and neck melanoma and Merkel
      cell cancer patients from August 1997 to August 2002. In all cases. technetium
      99m sulfur colloid was the radioactive tracer used by the nuclear medicine
      department to perform the lymphoscintograms. RESULTS: Of the 135 patients, 74
      underwent preoperative lymphoscintigraphy in preparation for performing a
      sentinel lymph node biopsy. Of these 74 patients, 5 (6.8%) were found to have
      nonlocalization of a sentinel node(s). Of the 5 patients who failed to localize,
      3 had primary lesions near the midline scalp, while 2 had primary lesions located
      on the cheek. Two of the 5 patients underwent reinjection of the radioisotope by
      the treating surgeon (WKS) but failed to further localize the radiotracer. All 5
      patients went on to have wide local excision of the primary cancer on the day of
      the lymphoscintogram, as well as undergoing intraoperative examination of all
      head and neck nodal basins with a handheld gamma detector. No focal areas of
      radiation were identified and no lymph nodes were biopsied. To date, 1 patient
      has developed distant metastases and has succumbed to her disease. The remaining
      4 patients are free of disease. CONCLUSION: In a series of 135 consecutive
      patients with head and neck cutaneous malignancies, 74 of whom were treated with
      preoperative lymphoscintograms, a nonlocalization rate of 6.8% was found. This is
      a significant rate of nonlocalization and reflects either the inherent difficulty
      in imaging the head and neck region and/or the possible rapid rate of dye washout
      via multiple lymphatic drainage pathways that exist in this location.

PMID- 15166977
TI  - Outcome of split-thickness skin grafts after external beam radiotherapy.
AB  - There are many technical considerations in patients who require radiotherapy
      after oncologic reconstruction. A traditional tenet is to avoid skin grafts in
      this setting. However, this is not always avoidable. Therefore, the objective of
      this study was to evaluate the wound healing and functional outcome of patients
      in the authors' institution whose skin grafts were subsequently irradiated. A
      retrospective analysis of all patients treated with split-thickness skin grafts
      and postoperative radiotherapy at Memorial Sloan-Kettering Cancer Center from
      1995 to 2002 was performed. Parameters evaluated included indications for skin
      graft, defect size, time to postoperative radiotherapy, total radiotherapy dose,
      delays and interruptions in radiotherapy, wound complications, and the need for
      further skin grafting. There were 30 patients (23 men, 7 women) with a mean
      defect size of 152 +/- 132 cm2. All split-thickness skin grafts were placed on
      healthy vascular tissue beds. In most instances (67%) skin grafts were used to
      cover muscle flaps. Median time to initial radiotherapy after grafting was 8
      weeks (range, 4-60 weeks). There was 1 delay and 4 interruptions in radiotherapy
      treatment. There were 2 partial skin graft losses (<20%) after radiation that
      healed with conservative treatment. There was 1 complete skin graft loss after
      radiotherapy that required regrafting. Split-thickness skin grafts can tolerate
      postoperative radiotherapy without significant complications. Postoperative
      external beam radiation can begin as early as 6 to 8 weeks after skin grafting.
      If the requirement for postoperative radiotherapy is known, split-thickness
      grafts should ideally be placed on well-vascularized muscle beds. Minor skin
      graft loss resulting from postoperative radiotherapy can usually be treated
      conservatively without the need for additional surgery.

PMID- 15166979
TI  - Small incision transcutaneous levator aponeurotic repair for blepharoptosis.
AB  - PURPOSE: Patients presenting with blepharoptosis due to disinsertion or thinning
      of the levator aponeurosis require surgical repair. A minimally invasive approach
      directed specifically at the levator aponeurotic anatomic defect may provide
      benefits to the patient. Proposed advantages of a small eyelid incision (8-13 mm)
      include less local anesthetic and tissue distortion, less ecchymosis and edema,
      decreased operative times, a shortened recovery period, and improved surgical
      results. We describe our results with the use of a small incision ptosis repair
      in select patients. SUBJECT AND METHODS: A retrospective chart review between
      January 2000 and September 2001 included 91 patients and 118 eyelids with
      blepharoptosis due to aponeurotic disinsertion, corrected by a minimally invasive
      approach. The small incision technique comprised levator aponeurotic resection
      and advancement. Pre- and postoperative upper eyelid marginal reflex distances
      (MRD1), eyelid contour, need for reoperation, and complications (overcorrection,
      undercorrection, hematoma, and infection) were recorded. RESULTS: The average
      preoperative MRD1 measured 0.5 +/- 1.1 mm, with a range of -2.0 to 2.5 mm. The
      average postoperative MRD1 measured 2.6 +/- 0.8 mm, with a range of 1 to 5.5 mm
      (P < 0.0001). Of the 118 eyelids corrected by a small incision technique, there
      were 4 overcorrections, 3 undercorrections, 1 failure, 1 postoperative ptosis
      procedure of the contralateral upper eyelid secondary to Hering's law ptosis, and
      4 patients requesting surgical treatment of dermatochalasis. No symptomatic dry
      eye, exposure keratopathy, or other complication resulted in association with the
      overcorrections. No contour abnormalities, infections, hematomas, or other
      complications were noted. CONCLUSION: Our experience suggests that utilization of
      a small skin incision is safe, precise, and efficient and allows for more rapid
      recovery from surgery. The authors note a decreased incidence of reoperation and
      postoperative complaints compared with historical larger-incision cases.

PMID- 15166981
TI  - Percutaneous technique for reduction of complex metacarpophalangeal dislocations.
AB  - Historically, complex metacarpophalangeal (MCP) joint dislocations have
      necessitated open surgical management by either a volar or dorsal approach. The
      authors describe a relatively simple and reliable percutaneous technique to treat
      these complex MCP dislocations, with results comparable with open surgical
      reduction. This minimally invasive technique can be performed in the emergency
      room setting, thereby avoiding the cost and morbidity associated with an open
      procedure in the operating room. From 1996 to 2003, the percutaneous technique
      was performed on 4 patients with complex MCP joint dislocations. Three patients
      underwent percutaneous reduction in an operating room whereas the fourth patient
      was reduced in the emergency room. Successful reduction was attained on the first
      attempt in all 4 patients without complications. All dislocations were stable
      after reduction. Near full, painless range of motion was achieved in all 4
      patients and there were no cases of recurrent instability. All patients were
      satisfied with their results.

PMID- 15166983
TI  - Rebalancing of forces as an adjunct to resection suspension arthroplasty for
      trapezial osteoarthritis.
AB  - The carpometacarpal (CM) joint of the thumb is commonly affected by
      osteoarthritis. The strength required for a first CM ligament reconstruction
      depends on the forces across the joint. If these forces are rebalanced to reduce
      the requirements necessary to prevent subluxation, reconstructive requirements
      are lowered and surgical dissections reduced. A method to achieve this goal based
      on Landsmeer's zig-zag compression concept is presented. Fifteen consecutive
      patients (11 women; mean age, 63 years) with pantrapezial osteoarthritis were
      selected over a 2-year period to undergo this novel procedure. After standard
      trapezial resection, trapezoidal hemiresection was performed, allowing for medial
      movement of the first metacarpal base. Following the zig-zag concept, the first
      metacarpophalangeal joint reciprocally fell into flexion, decreasing forces
      causing subluxation of the first metacarpal base. A saddle-like suspension under
      the metacarpal base was created using the trapezial capsule. All 15 patients had
      excellent outcomes with elimination of pain, early recovery of mobility and
      power, and no recurrent subluxations. The durability of the procedure was
      confirmed clinically and radiologically. The medial relocation of the first
      metacarpal base rebalances and attenuates the normal deforming forces thereby
      eliminating the need for a strong CM ligament reconstruction.

PMID- 15166985
TI  - Neurosurgical reconstruction with acellular cadaveric dermal matrix.
AB  - Acellular cadaveric dermal matrix (ACDM) is processed from human cadaver skin
      (AlloDerm; Life Cell Corp., Branchburg, NJ). It does not require an immediate
      blood supply but can transmit essential interstitial fluids for nourishment of
      overlying tissues. A number of neurosurgical reconstructions have required the
      use of tissue that fills these specifications. The material has been used most
      recently for reconstruction of dura during craniotomies when primary closure is
      not possible or harvesting from an autologous site is not available. Because ACDM
      is harvested from nonneurologic cadaveric tissues and because the cellular and
      antigenic elements have been removed from the matrix, prion diseases are not a
      transmission risk. We present 6 examples of previously unreported uses of ACDM
      for successful repair of meningomyelocele, cauda equina, encephalocele,
      cerebrospinal fluid fistula, and neuroma. We propose the use of ACDM as a
      valuable tool in neurosurgical reconstruction.

PMID- 15166989
TI  - Ex vivo transduction of microvascular free flaps for localized peptide delivery.
AB  - Gene therapy is a promising modality for the treatment of soft tissue
      malignancies. Our laboratory has developed a novel technique of gene transfer
      using microvascular free flaps that addresses many of the current barriers
      preventing gene therapy from achieving widespread clinical use. Our previous work
      has demonstrated our ability to transduce free flaps with an adenovirus encoding
      the reporter gene lacZ. In this current study, we show that microvascular free
      flaps can be transduced with an adenovirus encoding the angiogenesis inhibitor
      endostatin with high levels of local flap expression. These transduced free flaps
      were able to serve as "biologic pumps" and were able to secrete endostatin into
      the serum as demonstrated by enzyme-linked immunosorbent assay. This form of
      "biologic brachytherapy" could provide a novel approach for the continuous
      delivery of therapeutic genes to a localized area while avoiding many of the
      practical obstacles currently limiting gene therapy.

PMID- 15166987
TI  - Timing of percutaneous endoscopic gastrostomy tube placement after cervical
      esophageal reconstruction with free jejunal transfer.
AB  - The timing of percutaneous endoscopic gastrostomy (PEG) tube placement in
      patients who undergo cervical esophageal reconstruction using free jejunal
      transfer is controversial. The purpose of this study was to review the authors'
      experience with pharyngeal reconstruction using free jejunal transfer to
      establish useful guidelines for enteral tube placement. A retrospective analysis
      of all patients treated with free jejunal autografts for reconstruction of
      cervical esophageal defects during a 12-year period was performed. A total of 105
      patients underwent 108 esophageal reconstructions using these techniques. Sixty
      three patients (60%) did not have enteral tube placement at any time, whereas 42
      patients had gastrostomy or PEG tubes placed preoperatively (n = 12),
      intraoperatively (n = 8), or postoperatively. The majority of patients were able
      to resume per-oral feeds and avoid long-term tube feeds (86.7%). Most patients
      who underwent preoperative or intraoperative enteral tube feed placement had them
      removed postoperatively (82%). Only patients who required postoperative placement
      of feeding tubes required prolonged feeding tube support. In conclusion, most
      patients who undergo esophageal reconstruction using free jejunal transfer
      recover the ability to swallow and maintain adequate nutrition without
      supplemental enteral tube feeds. Preoperative gastrostomy tube placement is not
      necessary in most patients unless severe preoperative nutritional compromise is
      present.

PMID- 15166991
TI  - Bone morphogenic protein-2 gene therapy for mandibular distraction osteogenesis.
AB  - Distraction osteogenesis (DO) requires a long consolidation period and has a low
      but real failure rate. Bone morphogenic proteins (BMPs) accelerate bone
      deposition in fractures and critical-sized bone defects, but their effects on
      mandibular DO are unknown. We investigated the effect of local delivery of
      adenovirus containing the gene for BMP-2 (Adbmp-2) on mandibular DO in a rat
      model. Rats (n = 54) were distracted to 3 mm over 6 days. At the start of
      consolidation (POD 10), Adbmp-2 or adenovirus containing the lacZgene (AdlacZ)
      was injected directly into the distraction zone. After 1, 2, and 4 weeks of
      consolidation, mandibles were evaluated for amount of bone deposition. Adbmp-2
      treated specimens demonstrated an increased amount of new bone formation by
      radiographic, histologic, and histomorphometric analysis. This study demonstrates
      that local, adenovirally-mediated delivery of BMP-2 can increase bone deposition
      during DO, potentially shortening consolidation and enhancing DO in poorly
      healing mandibles, such as occurs postirradiation.

PMID- 15166993
TI  - Hybrid constructs for craniofacial reconstruction: sustained gene delivery using
      demineralized bone matrix putty.
AB  - These experiments evaluate the efficacy of a demineralized bone matrix putty
      engineered as a hybrid construct for sustained, site-directed gene transfer using
      an adenoviral vector. In vitro experiments were performed to evaluate the optimal
      dosing for gene transfer to fetal calvarial osteoblasts and dural cells and for
      the sustainability of gene transfer from the hybrid constructs. In the dosing
      experiments, hybrid constructs were created by combining 0.5 mL of demineralized
      bone matrix putty (DBX; SYNTHES Maxillofacial, Monument, CO) with 1 x 10(8), 1 x
      10(7), or 1 x 10(6) particle-forming units (PFU) of an adenoviral vector carrying
      the gene encoding green fluorescent protein (AdGFP). These constructs were then
      placed in direct contact, or in transwell coculture, with fetal murine calvarial
      osteoblasts or dural cells at a multiplicity of infection (MOI = viral
      particle/cell ratio) of 1000, 100, and 10. The sustainability of gene transfer
      was tested through transfer of the hybrid construct to wells containing
      untransfected cells every 24 hours for 30 days. In both experiments, gene
      transfer was determined through the visualization of GFP using fluorescence light
      microscopy 24 hours after the onset of transfection. Optimal dosing for gene
      transfer occurred at an MOI of 10 for calvarial osteoblasts and 100 for dural
      cells. At greater concentrations, toxicity was observed in the majority of
      samples. Gene transfer to fetal dural cells and calvarial osteoblasts was
      sustained throughout the 30-day period. These experiments suggest that adenoviral
      vectors could be successfully incorporated within demineralized bone matrix to
      provide effective, sustained, site-directed gene transfer.

PMID- 15166995
TI  - Silicone breast implants and connective tissue disease: an updated review of the
      epidemiologic evidence.
AB  - Numerous meta-analyses, weight-of-the-evidence, and critical reviews have
      summarized data from case-control and cohort studies, published through 1999,
      which have been conducted to evaluate the potential association between cosmetic
      silicone breast implants and the occurrence of well-defined connective tissue
      diseases, as well as a hypothesized new atypical disease, which does not fulfill
      established diagnostic criteria for any known connective tissue disease. These
      reviews have unanimously concluded that there is no evidence of an association
      between breast implants and any of the traditional connective tissue diseases
      evaluated individually or combined or atypical connective tissue disease. We have
      performed an updated review of the results of epidemiologic studies published
      since 1999. Two long-term follow-up studies of women with breast implants in
      Denmark and a retrospective cohort study in Australia found no excess of definite
      connective tissue disease, including rheumatoid arthritis, systemic sclerosis,
      systemic lupus erythematosus and Sjogren's syndrome, among women with cosmetic
      breast implants compared with breast reduction or other plastic surgery controls
      or women in the general population. No consistent evidence was observed of
      increased risk of definite connective tissue disease in women with extracapsular
      ruptures in 2 studies which evaluated risk by rupture status among women with
      cosmetic breast implants. The results of several studies provide no evidence of a
      higher frequency of undefined connective tissue disease among women with cosmetic
      breast implants or of a rheumatic symptom profile unique to these women and/or
      indicative of a specific atypical connective tissue disease. In conclusion, the
      most recent epidemiologic investigations have been remarkably consistent with
      earlier epidemiologic studies in finding no evidence of an excess of any
      individual connective tissue disease or all connective tissue diseases combined,
      including both established and atypical or undefined connective tissue disease,
      among women with cosmetic silicone breast implants. Thus, the conclusions reached
      in earlier independent reviews have not changed based on data published during
      the subsequent years.

PMID- 15166996
TI  - Treatment of earlobe keloids using the cobalt 60 teletherapy unit.
AB  - The purpose of this study was to develop an easily accessible technique for the
      delivery of postoperative radiotherapy for the treatment of earlobe keloids.
      Forty-seven earlobe keloids were given postoperative radiation using the smallest
      achievable half field Telecobalt technique. Results showed 41 (87.2%) of treated
      patients' postoperative scars remained free from recurrent keloid formation.
      Acute reactions were minimal and patient compliance was excellent. In conclusion,
      the technique described in this study for the delivery of postoperative radiation
      to earlobe keloids should be readily available in areas of high prevalence.
      Results are comparable to previously used radiotherapy techniques.

PMID- 15166997
TI  - Keloid scars are formed by polyclonal fibroblasts.
AB  - We hypothesized that keloids are composed of polyclonal fibroblasts and are not
      tumors derived from a single abnormal cell. That is, they are not monoclonal
      fibroblast neoplasms but rather are formed by intrinsically normal polyclonal
      fibroblasts that are responding to an abnormal extracellular signal. This
      hypothesis was tested using a polymerase chain reaction-based assay to examine X
      chromosome inactivation and thereby determine clonality of keloid tissue. Six of
      12 keloid samples analyzed were polyclonal. Three were genetically
      noninformative, and 3 were monoclonal. The presence of polyclonal specimens is
      consistent with our hypothesis and predicts that keloids result from
      intrinsically normal fibroblasts that are responding to an abnormal extracellular
      signal. This result can guide future genetic and molecular studies to identify
      this proposed abnormal regulatory signal, which we expect to be an important
      regulator of normal and diseased scarring.

PMID- 15166998
TI  - Regulation of inducible nitric oxide synthase in ischemic preconditioning of
      muscle flap in a rat model.
AB  - PURPOSE: Ischemic preconditioning has been shown to influence flap tolerance to
      prolonged ischemia. Nitric oxide (NO) synthesis is one of the proposed mechanisms
      involved in ischemic preconditioning. In this study, the molecular marker of NO
      is examined in correlation with ischemic preconditioning on improving muscle flap
      survival. METHODS: Fifty male Sprague-Dawley rats were randomized into
      experimental and control groups. The gracilis muscle flap with femoral vascular
      pedicle was used as a flap model. Ischemic preconditioning consisted of 3
      sequences of clamping the pedicle for 10 minutes followed by 10 minutes of
      reperfusion for a total of 1 hour. In part I, the experimental group (n = 10)
      underwent ischemic preconditioning for 1 hour. In the control group (n = 10), the
      flaps were dissected without clamping of the pedicle. Both groups were then
      subjected to 4 hours of global ischemia by continuous pedicle clamping, after
      which the flaps were sutured to their beds. On postoperative day 3, flap survival
      was determined by gross and histologic examinations. The evaluators were blinded
      to the treatment. In part II, the experimental group (n = 12) underwent ischemic
      preconditioning, while the control group (n = 12) did not. The flaps from each
      group were harvested for inducible nitric oxide synthase (iNOS) gene expression
      using reverse transcriptase-polymerase chain reaction at the end of 1 hour after
      reperfusion and at 4 hours of global ischemia. RESULTS: The results indicated a
      significantly higher survival rate in the experimental group than in the control
      group (90 versus 50%, P < 0.05). iNOS gene expression was significantly higher in
      the experimental group than in the control group at 1 hour after ischemic
      preconditioning (0.73+/-0.18 versus 0.26+/-0.11, P < 0.01). However, after 4
      hours of global ischemia, iNOS expression in the control group was statistically
      higher than in the experimental group (0.83+/-0.16 versus 0.26+/-0.07, P < 0.01).
      CONCLUSIONS: We conclude that ischemic preconditioning can enhance flap tolerance
      to ischemia-reperfusion injury and improve flap viability rate. This study
      provides evidence that the regulation of NOS may play a role in ischemic
      preconditioning phenomenon and warrants further investigation.

PMID- 15166999
TI  - Microsurgical replantation of a small segment of thumb volar skin.
AB  - This report presents a case of microsurgical replantation of a volar skin segment
      of the thumb. In a 24-year-old patient, a heavy object falling over the dominant
      thumb resulted in a crush-avulsion injury of a pure skin segment measuring 4 x 2
      cm. Examination revealed that the distal fingertip as well as the bone-tendon
      structures remained intact. Exploration demonstrated that both neurovascular
      bundles were included in the avulsed skin segment. Microsurgical replantation was
      achieved successfully, repairing the radial digital artery at both ends with vein
      grafts as well as anastomosing a palmar vein. Both digital nerves were coapted
      proximally and distally. An excellent functional and cosmetic result was
      accomplished with a good sensory recovery. The authors conclude that
      microsurgical replantation should be attempted in cases of more proximal pure
      skin avulsions, even if the injury spares distal fingertip tissue or bone-tendon
      units. In such cases, replantation is superior to any other method of
      reconstruction. Liberal use of vein grafts is crucial to achieve success.

PMID- 15167001
TI  - Pneumatic vagina dilator.

PMID- 15167000
TI  - Wedge excision of the nail fold in the treatment of ingrown toenail.
AB  - Many treatment modalities of ingrown toenail are reported in the literature,
      often associated with unacceptably high recurrence rate. The authors present
      their technique, which aims at reducing the convexity of the nail fold. After
      complete removal of the nail plate and accurate debridement of the granulomatous
      tissue, a wedge-shaped ellipsis of skin and subcutaneous tissue, lateral to the
      affected nail fold, is removed. Approximation of the margins of the resulting
      defect determines eversion of the nail fold. One hundred twenty ingrown toenails
      were treated with the wedge excision of the nail fold at the outpatient clinic of
      the department of plastic surgery, Campus Bio-Medico University, Rome, Italy,
      between January 1998 and January 2002. Six recurrences were observed. In addition
      to the high cure rate, short postoperative pain duration, and morbidity as well
      as low risk of postoperative infection, the remarkable esthetic results
      achievable with this method are indicated.

PMID- 15167002
TI  - Dances with Wolfe.

PMID- 15167003
TI  - Single-stage achilles tendon reconstruction.

PMID- 15167004
TI  - The use of a towel clamp as a complementary instrument for manual fat harvest.

PMID- 15167005
TI  - Honey therapy.

PMID- 15167007
TI  - Allelic imbalance mapped to 6q14.1 is associated with loss of expression of 5-HT
      receptor 1B in non-Hodgkin lymphomas.
AB  - Previous studies on lymphomas suggested that the long arm of chromosome 6 harbors
      1 or more tumor suppressor genes. This study analyzed the status of 25
      microsatellite markers in 39 cases, including 9 nodal and 30 extranodal, of non
      Hodgkin lymphomas. Thirty of the 39 cases (77%) showed abnormality in at least 1
      of the markers. Of the 655 informative results, 135 (20%) were abnormal. These
      included 5 homozygous deletions, 91 allelic imbalances (AI), and 38
      microsatellite instability. The 2 commonest regions of abnormality were mapped to
      6q14.1 and 6q27. There was no significant difference in the frequency of these
      regional losses between nodal and extranodal lymphomas, B-or T-cell lineage, and
      association with Epstein-Barr virus. The first common deletion region at 6q14.1
      is flanked by the HTR1B (5-hydroxytryptamine receptor 1B) gene proximally and a
      novel unknown gene. AI in the region was found associated with loss of expression
      HTR1B by RT-PCR. The deletion region at 6q27 was narrowed to approximately 3Mb
      and maximal at marker D6S386. This locus includes the recently identified SMOC2
      (secreted modular calcium-binding protein 2), AF6, and DLL1 (human delta-like 1
      protein) genes. RT-PCR analyses of AF6 and DLL1 expression showed poor
      correlation with the AI results.

PMID- 15167006
TI  - Epstein-Barr Virus (EBV) DNA in plasma is not encapsidated in patients with EBV
      related malignancies.
AB  - Epstein-Barr Virus (EBV), a ubiquitous gamma herpes virus, infects more than 95%
      of the human population before adulthood. Life-long persistence, usually without
      adverse health consequences, relies on a balance between viral latency, viral
      replication, and host immune response. Patients with EBV-related disease often
      have high levels of EBV DNA in their plasma. This study addresses whether this
      circulating, cell-free EBV DNA is encapsidated in virions or exists as naked
      genomes. First, an assay was developed, combining DNase I and quantitative real
      time PCR, to discriminate encapsidated from naked EBV DNA. EBV DNA was almost
      always naked in the plasma of AIDS-related lymphoma patients (n = 11) and
      immunosuppressed/posttransplantation patients (n = 8). In contrast, infectious
      mononucleosis patients (n = 30) often had a mixture of encapsidated and naked EBV
      DNA. These findings may be important in understanding how viral load relates to
      disease status and in predicting response to nucleoside analogs and other
      antiviral therapies.

PMID- 15167008
TI  - A common clonal origin of nodal marginal zone B-cell lymphoma and plasma cell
      myeloma demonstrating different immunophenotypes: a case report of composite
      lymphoma.
AB  - We demonstrated an 83-year-old male case of composite lymphoma. Before 18 years,
      he was diagnosed with nodal marginal zone B-cell lymphoma in the cervical lymph
      node. Peripheral blood showed anemia and IgA (kappa)-type monoclonal gammopathy
      (IgA; 3,625 mg/dL). Bone marrow aspiration biopsy exhibited plasma cell myeloma,
      in which atypical plasma cells were positive for cytoplasmic IgA (kappa) and
      atypical lymphoid cells intermingled were positive for CD20. In contrast,
      cervical lymph node biopsy revealed nodal marginal zone B-cell lymphoma, in which
      lymphoma cells were positive for cytoplasmic IgG (lambda). Southern blotting
      analysis of the IgH gene showed same clonal rearrangement band in both lymph node
      and bone marrow samples and additional band in the bone marrow. Sequence analyses
      of the IgH gene showed an identical sequence of CDR3 in both samples. Thus, we
      demonstrated a common clonal origin of composite lymphoma comprising nodal
      marginal zone B-cell lymphoma and plasma cell myeloma. Nodal marginal zone B-cell
      lymphoma recurred in cervical lymph node and involved into the bone marrow,
      differentiating into plasma cell myeloma in which Ig isotype switched and
      monoclonal gammopathy developed. Sequence analysis of the IgH gene was a powerful
      tool for determination of clonal origin.

PMID- 15167009
TI  - Deregulation of the G1 to S-phase cell cycle checkpoint is involved in the
      pathogenesis of human osteosarcoma.
AB  - Osteosarcoma (OS) displays complex karyotypes with numerical changes as well as
      structural abnormalities suggesting that several oncogenes and tumor suppressor
      genes may be implicated in the biology of OS. The aim of our study was to
      investigate the possible implication of the molecular alterations of the G1 to S
      phase checkpoint genes in the pathogenesis of OS. We analyzed samples from 29
      patients and found molecular alterations of the RB and TP53 genes in 6 (21%) and
      3 (10%) cases, respectively. Homozygous deletion of the INK4A/ARF locus and
      methylation of INK4A was detected in 3 (10%) and 2 (7%) cases, respectively. CDK4
      and MDM2 co-amplification was observed in 1 case (3%). Cyclin D3 is
      differentially expressed in a greater proportion than D1- and D2-type cyclins.
      Cytogenetically, all cases had complex karyotypes being especially significant
      the losses of the chromosomes 4, 13, and 17. As a whole, 11 of 29 (38%) analyzed
      OS presented alterations in some of the analyzed G1 to S-phase checkpoint genes.
      These alterations were more frequently present in adults (P = 0.032). All
      patients with genetic alterations in the G1/S-phase checkpoint died during their
      clinical follow-up, whereas more than 53% of the remaining cases were alive in
      this period (P = 0.007). Hence, in the pathogenesis of human OS, deregulation of
      the G1/S checkpoint genes, especially RB, TP53, and INK4/ARF locus, plays an
      important role and defines a subgroup of patients with a poor outcome.

PMID- 15167011
TI  - Formalin-fixed and paraffin-embedded nodal non-Hodgkin's lymphomas demonstrate
      the same chromosome changes as those found in frozen samples: a comparative study
      using interphase fluorescence in situ hybridization.
AB  - Cytogenetic studies in lymphomas classically require fresh or frozen tissue,
      whereas in many instances only paraffin-embedded biopsies are available. We
      applied an interphase FISH assay on nuclei extracted from thick paraffin sections
      to determine accuracy of molecular cytogenetics in such samples. Twenty-three
      lymphoma samples and 4 reactive lymph nodes were tested with various commercially
      available DNA probes, and hybridization patterns were compared with those
      obtained on frozen nuclei counterparts. Successful hybridization with all probes
      tested was observed for 23/27 (85%) paraffin-embedded tissues and for all (100%)
      frozen samples, and cut-off levels defining positivity were superimposable for
      both situations. Chromosome changes were detected in the same way, without any
      false-positive or false-negative cases. Hybridization signals observed on dewaxed
      samples were either those classically expected to define the relevant chromosome
      change or were atypical: all atypical changes could be demonstrated also into
      nuclei from the frozen counterpart. Moreover, all typical and atypical chromosome
      changes observed on frozen nuclei were also detected in paraffin-embedded
      tissues. Our study shows that our interphase FISH assay performed on paraffin
      embedded samples is a valuable alternate to conventional methods to ascertain
      diagnosis of lymphomas as to include patients into therapeutic trials.

PMID- 15167010
TI  - Myxoid liposarcoma with adipocytic maturation: detection of TLS/CHOP fusion gene
      transcript.
AB  - This report describes a 49-year-old woman with a well-circumscribed nodule of
      liposarcoma. The patient noticed a soft, slowly growing mass at the right sural
      region. Both axial computed tomography and magnetic resonance imaging revealed a
      soft tissue tumor consisting of nonfatty lesion measuring 5 x 3 x 3 cm
      circumscribed by a 1-cm thickened fatty area. Histologically, the tumor was made
      of 2 distinct components: the inner component of the tumor was a classic myxoid
      liposarcoma with numerous lipoblasts; the outer component was a lipoma-like
      lesion consisting of mature adipocytes without atypical nuclei.
      Immunohistochemically, MDM2 overexpression was observed and p53 immunophenotype
      was negative in both components. Molecular analysis revealed that type 1 TLS/
      CHOP fusion gene transcript, characteristic of myxoid/round cell liposarcoma, was
      detected in both areas.

PMID- 15167012
TI  - LM-PCR permits highly representative whole genome amplification of DNA isolated
      from small number of cells and paraffin-embedded tumor tissue sections.
AB  - Analysis of genetic changes is often hampered by insufficient starting DNA from
      limited clinical tissue specimens. We employed ligation-mediated PCR (LM-PCR) for
      global amplification of the genome to overcome this limitation, generating up to
      5 microg of representative amplicons of genomic DNA from as little as one cell.
      We demonstrate successful global genome amplification in high-quality starting
      DNA source like laser-captured cultured cells, as well as partially degraded
      starting DNA from old formalin-fixed paraffin-embedded tissue sections. This
      process generates adaptor-tailed templates that can be repeatedly amplified
      almost ad infinitum. We have further modified this technique such that, instead
      of a single endonuclease digest, we can achieve higher amplicon coverage by
      combining 3 endonuclease digests prior to LM-PCR. As tested by examining
      amplification of STS sequences scattered genome-wide, the coverage was improved
      from the published 70% to 96%. The faithful representation of global losses and
      gains in the amplified genomic DNA was confirmed by array-comparative genomic
      hybridization. Further, we exemplify the utility of this technique for finer p53
      point mutation analysis by PCR-SSCP. This technique is thus a clinically useful
      tool for globally amplifying and archiving DNA from finite sources like paraffin
      tissue sections, providing a potentially unlimited resource for genetic analyses.

PMID- 15167013
TI  - Impact of fixative on recovery of mRNA from paraffin-embedded tissue.
AB  - Due to the evolution of advanced tissue-analysis tools, such as proteomics and
      functional and structural genomics, the demands for handling and preserving
      samples are changing. For gene expression analysis, the presence of intact and
      extractable messenger RNA in the test material is mandatory. To find an optimal
      fixative for tissues aimed for such analyses, we evaluated the morphology-,
      protein antigen-, and RNA-maintaining abilities of 2 precipitating tissue
      fixatives, methanol-acetone and Carnoy's. Both fixatives preserved the morphology
      and protein epitopes of tissues and allowed extraction of total RNA that was of
      significantly higher quality than RNA extracted from formalin-fixed tissue.
      Carnoy's fixative performed better than methanol-acetone in maintaining the
      integrity of RNA, especially when the fixed, paraffin-embedded tissue blocks were
      stored at room temperature for more than 3 months. Total RNA extracted from
      epithelial cells microdissected from Carnoy's-fixed tissue samples contained
      intact template for up to a 977-base pair (bp) amplicon for beta-actin. Because
      of the emerging role of gene expression analyses in research, and in clinical
      work in the near future, an RNA-preserving fixative should replace formalin as
      the primary human tissue fixative. According to our data, Carnoy's fixative is an
      excellent candidate for a new primary fixing reagent for human tissue samples.

PMID- 15167014
TI  - Pediatricians advocating for children: an annotated bibliography.
AB  - PURPOSE OF REVIEW: Pediatricians have for many years been strong advocates for
      the health and safety of children. This article reviews the health literature to
      provide a historical perspective of advocacy efforts of pediatricians and
      examples of advocacy for patients at the bedside, in the community, and through
      local, state, and federal legislation, as well as policymaking. Studying these
      advocacy activities and incorporating them into pediatric practice and education
      of residents will surely result in stronger, healthier, safer, and happier
      children and families. RECENT FINDINGS: Some of the cited works relate to
      pediatric advocacy in general, and some relate to advocacy for specific pediatric
      topics. Also, articles relating to the education of medical students and
      pediatric residents are reviewed; they may be of benefit to educators who develop
      advocacy curriculum. SUMMARY: A review of the MEDLINE literature database from
      1966 through October 2003 was performed looking for the terms advocacy (child
      advocacy, consumer advocacy, legislative advocacy, patient advocacy), as well as
      advocacy education and training, and was limited to children from birth through
      18 years. The titles and many of the abstracts of 4580 articles were reviewed,
      and 104 articles were read in full. From these, 68 were selected for review here;
      they were thought to be of particular interest to practicing pediatricians and
      pediatric educators.

PMID- 15167015
TI  - Exercise, stress, and inflammation in the growing child: from the bench to the
      playground.
AB  - PURPOSE OF REVIEW: It is becoming increasingly clear that physical activity in
      children plays a critical role in growth and development, therapy for certain
      chronic diseases and disabilities, and in the pediatric origins of a variety of
      bone, metabolic, and cardiovascular diseases. New mechanistic insights have
      created the opportunity for a phase shift in understanding of the links between
      exercise and health in the context of the growing child. RECENT FINDINGS:
      Exercise even in healthy children profoundly alters stress, immune, and
      inflammatory mediators including peripheral blood mononuclear cells and
      circulating pro- and anti-inflammatory cytokines (like interleukin-6). Moreover,
      exercise even in healthy adults stimulates the production of reactive oxygen
      species (ROS) and mediators that attenuate them. Oxidative stress, in turn,
      alters growth and stress mediators. Both ROS and stress/inflammatory factors
      interact with powerful growth mediators like growth hormone and insulinlike
      growth factor-I. These findings suggest specific ways in which the balance
      between pro- and anti-inflammatory, catabolic, and anabolic factors associated
      with exercise can influence health and growth in children. SUMMARY: To address
      the current epidemic of physical inactivity and obesity in children and to
      optimize the therapeutic effects of exercise in children with disease and
      disability will require real changes in environments (eg, schools and
      playgrounds); innovative approaches to rehabilitation of children with chronic
      disease and disability; and enlightened training of child health professionals.
      Identifying novel exercise mechanisms involving stress, inflammation, and growth
      factors will help guide these efforts.

PMID- 15167016
TI  - Approaches in the management of acute respiratory failure in children.
AB  - PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress
      syndrome (ARDS) are conditions that are associated with significant morbidity and
      mortality in children. There have been no advances in preventing ARDS, but this
      review highlights strategies directed at minimizing ventilator-induced lung
      injury and other new adjunctive therapies in the care of these patients. RECENT
      FINDINGS: High-frequency oscillatory ventilation, airway pressure release
      ventilation, and partial liquid ventilation are potential protective ventilatory
      modes for children with ALI or ARDS. Recruitment maneuvers, prone positioning,
      and kinetic therapy are all reported to improve oxygenation by opening the lung
      while positive end-expiratory pressure maintains functional residual capacity.
      Inhaled nitric oxide and surfactant are used to reduce inspired oxygen
      concentration and facilitate gas exchange, but their efficacy in ARDS continues
      to be investigated. Also, early investigations suggest that a specialized enteral
      formula can be a useful adjunctive therapy by reducing lung inflammation and
      improving oxygenation. When mechanical ventilation and adjunctive therapies fail,
      extracorporeal life support continues to be used as a rescue therapy. SUMMARY: It
      is likely that a combination of these therapies will maximize treatment and
      clinical outcomes in the future, but the only way that will be proven is through
      large controlled clinical trials in pediatric patients.

PMID- 15167017
TI  - Current concepts in asthma treatment in children.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present current literature
      related to the management of childhood asthma. RECENT FINDINGS: Persistent asthma
      is now considered an inflammatory airways disease. Inhaled corticosteroids are
      recognized as the preferred long-term control medication. New classes of
      medications have been introduced during the last 5 years, including leukotriene
      modifiers, long-acting beta-adrenergic agonists, combination inhaled
      corticosteroids with long-acting beta-adrenergic agonists, and anti-IgE. Research
      is also being directed to understand the early onset of asthma. SUMMARY:
      Management of childhood asthma is now being directed to early recognition and
      early intervention. Recent updates in the asthma guidelines prompt clinicians to
      consider intervention with antiinflammatory therapy, preferably inhaled
      corticosteroids, in children who have frequent asthma exacerbations and a risk
      profile for persistent asthma. In children with persistent asthma, inhaled
      corticosteroids are recognized as the preferred antiinflammatory therapy. Health
      care systems that have adapted this approach have recognized the benefits of
      reduced hospitalizations and urgent care visits. Continued research is needed to
      identify asthma at a very early stage so that interventions can be directed to
      interrupting the development of this disease.

PMID- 15167018
TI  - New concepts in abnormalities of respiratory control in children.
AB  - PURPOSE OF REVIEW: Respiratory control disorders such as apnea of prematurity,
      apparent life-threatening events, sudden infant death syndrome, and central
      hypoventilation are relatively frequent conditions in the pediatric age range and
      are associated with substantial morbidity and mortality. The explosion of
      technological breakthroughs in biology and medicine has facilitated our
      understanding of the fundamental mechanisms that govern the development of brain
      regions underlying respiratory control functions. RECENT FINDINGS: Recent
      critically important discoveries encompass the identification of neurons that
      constitute the central respiratory rhythm generator in the brainstem, the
      conceptual framework allowing for many neurons located in multiple strategic
      regions within the brain to coordinate central chemosensitivity, the discovery of
      long-term and short-term plasticity in hypoxic ventilatory regulation, and the
      recent uncovering of specific gene mutations in children affected with congenital
      central hypoventilation syndrome. SUMMARY: While the developmental aspects of
      control breathing are only now being actively explored in the context of our
      current understanding, it is likely that such efforts will yield important novel
      approaches to the clinical and pharmacologic management of these disorders in the
      near future.

PMID- 15167019
TI  - Pediatric liver transplantation.
AB  - PURPOSE OF REVIEW: Pediatric liver transplantation is a challenging and exciting
      field for all healthcare providers involved with children who have end-stage
      liver disease. Graft and patient survival continue to improve due to improvements
      in medical, surgical, and anesthetic management, organ availability,
      immunosuppression, and identification and treatment of postoperative
      complications. This review will describe recent advances in pediatric liver
      transplantation. RECENT FINDINGS: Although pediatric cases only represent
      approximately 10% of the total patients on the waiting list, the number of deaths
      on the waiting list increased from 196 to 1753 between 1988 and 1999. Recently, a
      new pediatric liver allocation policy was instituted. The utilization of cut down
      "reduced" livers, split liver grafts, and living-related donors has provided more
      organs for pediatric patients. Newer immunosuppression regimens, including
      induction therapy, continue to have a significant impact on graft and patient
      survival. Excellence in peri-operative management and identification and
      treatment of complications or infections also has had an impact on graft and
      patient survival. Finally, investigation and analysis of the postoperative
      quality of life, for both the patient and parents, is being conducted. SUMMARY:
      Pediatric liver transplantation is a challenging and rewarding field with
      continued improvements in patient and graft survival. A multidisciplinary team
      approach coupled with improvements in organ availability, immunosuppression, and
      peri-operative management has had a dramatic impact on survival.

PMID- 15167020
TI  - Nutrition for the pediatric office: update on vitamins, infant feeding and food
      allergies.
AB  - PURPOSE OF REVIEW: Advances in the field of pediatric nutrition continue to help
      the pediatric office practitioner provide excellent clinical care to their
      patients. In 2003, several important papers were published in the field of
      clinical nutrition that are reviewed. RECENT FINDINGS: New recommendations by the
      American Academy of Pediatrics for vitamin D supplementation for breast-fed
      infants have been published that underscore the importance of routine
      supplementation with 200 IU vitamin D per day. Vitamin K should be provided (0.5
      to 1 mg intramuscularly) to all newborns. The authors also review original
      reports evaluating the role of long-chain polyunsaturated fatty acids in infant
      formulas, the duration of exclusive breast-feeding, and the natural history of
      food allergies. Some observational studies support exclusive breast-feeding for 6
      months. Data concerning the efficacy of long-chain polyunsaturated fatty acids
      are conflicting but do support the safety of these additives. SUMMARY: Regular
      supplementation with vitamin D, and newborn provision of vitamin K, are important
      nutritional interventions for infants and children.

PMID- 15167021
TI  - Bibliography. Current world literature. Pulmonology.

PMID- 15167022
TI  - Current treatment for laryngeal papillomatosis.

PMID- 15167023
TI  - Recent advances in laryngeal sensorimotor control for voice, speech and
      swallowing.
AB  - PURPOSE OF REVIEW: This article reviews advances in knowledge on laryngeal
      sensorimotor control affecting the assessment, understanding, and treatment of
      laryngeal motor control disorders in voice, speech, and swallowing. Three topics
      are covered: new knowledge on laryngeal innervation and central nervous system
      control from basic research studies, the role of laryngeal sensation in normal
      swallowing and dysphagia in patients, and new approaches to the restoration of
      laryngeal motor control after recurrent laryngeal nerve disorders. RECENT
      FINDINGS: A significant advance this year was tracing the efferent pathways from
      the cortex to the brainstem in monkeys. This provided new information on
      subcortical and brainstem connections in the laryngeal efferent pathways.
      Laryngeal sensory feedback continued to receive attention, and the role of
      sensory feedback in the control of the pharyngeal phase of swallowing is now well
      established. Further developments in neuromotor monitoring of the recurrent
      laryngeal nerve during thyroidectomy were seen, and a large case series
      recommended that these techniques become standard practice for surgery for
      thyroid benign recurrence or malignancy. Finally, the first tissue engineering
      papers in the field of vocal fold tissue and nerve restoration were published
      this year, beginning an exciting new approach to restoration of laryngeal motor
      control. SUMMARY: Considerable attention has been given to laryngeal muscle
      physiology, denervation, and sensation in neurolaryngology. Relatively limited
      understanding is available regarding the central nervous system integrative
      control of laryngeal function for speech, respiration, and swallowing.

PMID- 15167024
TI  - Aerodynamics, voice quality, and laryngeal image analysis of normal and
      pathologic voices.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe examinations of
      phonatory function and their relation to image analysis of the unilaterally
      immobile larynx. Special emphasis was placed on image analysis using three
      dimensional endoscopic images produced from CT scans. RECENT FINDINGS:
      Developments in modern image processing technique have led to the quantification
      of various aspects of vocal fold vibration. Stroboscopic images of the vocal fold
      were digitized and, subsequently, the glottal gap area, amplitude, and degree of
      bowing were analyzed quantitatively in relation to phonatory function. Vocal fold
      vibration was observed with the aid of videokymography, during which images from
      a single transverse line can be recorded. Successive line images were shown in
      real time on a monitor, with the time dimension displayed in the vertical
      direction. This system enabled the assessment of left-right asymmetries, open
      quotient, propagation of mucosal waves, and forth. Three-dimensional endoscopic
      images derived from multislice CT scans provided a novel method for evaluating
      morphologic characteristics of the laryngeal lumen in relation to phonatory
      function. The combination of three-dimensional endoscopy and coronal
      reconstructed images supplemented stroboscopic findings exemplified by
      differences in vertical position and thickness between the vocal folds. SUMMARY:
      Depth information about the vocal fold as well as the presence of paradoxic
      movement of the affected vocal fold and overadduction of the healthy vocal fold
      during phonation should be taken into account when surgical intervention to
      improve hoarseness resulting from unilateral vocal fold immobility is performed.
      Phonatory function tests, videostroboscopy, and laryngeal image analysis are
      prerequisites to achieving this goal.

PMID- 15167025
TI  - Diagnosis of laryngopharyngeal reflux.
AB  - PURPOSE OF REVIEW: Laryngopharyngeal reflux is of great interest to
      otolaryngologists, speech and language therapists, and gastroenterologists. This
      is a brief review of recent publications in the diagnosis of laryngopharyngeal
      reflux. RECENT FINDINGS: Otolaryngologic signs and symptoms can be found in 4 to
      10% of patients with gastroesophageal reflux and those presenting for ear, nose,
      and throat evaluations. Laryngeal signs are not pathognomonic for
      laryngopharyngeal reflux because many of these signs can be found in healthy
      volunteers. A combination of signs and symptoms should be sought before
      suspecting this diagnosis. Most investigators consider pH monitoring the best
      currently available instrument to diagnose gastroesophageal reflux, even though
      it is not considered to be 100% sensitive and specific. Studies in normal
      volunteers indicate that a minimal number of reflux episodes reach the
      hypopharynx. The correlation between laryngeal signs and symptoms and pH
      documented reflux is less than perfect, whereas the combination of pH testing and
      signs and symptoms is better in detecting patients with a favorable response to
      acid-suppressing therapy. Using an empiric trial of high-dose proton pump
      inhibitors over a prolonged period of time to diagnose laryngopharyngeal reflux
      is supported mainly by uncontrolled studies. To date, double-blind, placebo
      controlled studies suggest that empiric trials of proton pump inhibitors may not
      have high accuracy for the diagnosis of laryngopharyngeal reflux. SUMMARY:
      Multidisciplinary trials are needed to establish the optimal combination of sign
      and symptom scores, reflux monitoring results, and empiric treatment trials for
      the most accurate diagnosis of laryngopharyngeal reflux.

PMID- 15167026
TI  - The impact of hormonal fluctuations on female vocal folds.
AB  - PURPOSE OF REVIEW: Sex hormone fluctuations were shown to affect female vocal
      folds and laryngeal function. Laryngeal changes are evident throughout the span
      of life, starting at puberty with the arousal of the hormonal system, fluctuating
      systematically during the reproductive years with the menstrual cycle, and then
      changing again with the decline of hormonal activity at menopause. This paper
      reviews recent developments in this field. RECENT FINDINGS: Early studies that
      explored this relation were based merely on subjective impressions of voice
      quality, recent studies have used more objective tools for examining this
      relation, including histologic observations, stroboscope, electroglottography
      (EGG), and computerized acoustic analyses. In these studies, the larynx was shown
      to be a hormonal target organ and, as such, sex hormones affect its morphology,
      histology, and function, similar to their effect on the genitals and other
      organs. SUMMARY: Examining the relation between sex hormones and the larynx could
      assist in understanding the mechanisms of voice production, and it could provide
      the clinician with supplemental diagnostic information on different medical
      conditions.

PMID- 15167027
TI  - The role of biofilms in otolaryngologic infections.
AB  - PURPOSE OF REVIEW: Bacterial biofilms have recently been shown to be important in
      diseases of the head and neck. Because the concept of biofilms is novel to most
      practitioners, it is important to gain a basic understanding of biofilms and to
      recognize that strategies developed to treat planktonic bacteria are ineffective
      against bacteria in a biofilm. RECENT FINDINGS: Bacteria preferentially exist in
      complex, surface-attached organizations known as biofilms. Bacteria in biofilms
      express a different set of genes than their planktonic counterparts and have
      markedly different phenotypes. Biofilm bacteria communicate with each other, and
      have mechanisms to diffuse nutrients and dispose of waste. Biofilms provide
      bacteria with distinct advantages, including antimicrobial resistance and
      protection from host defenses. Thus, bacteria exist in a far more complex fashion
      than previously thought and can best be thought of as "self-assembling
      multicellular communities." Although a focus on the planktonic form of bacteria
      has been useful in understanding acute infections, chronic infections are much
      better understood as biofilm illnesses. Biofilms have been shown to be involved
      in chronic otitis media, chronic tonsillitis, cholesteatoma, and device
      associated infections. SUMMARY: Now that basic research has demonstrated that the
      vast majority of bacteria exist in biofilms, the biofilm concept of disease is
      beginning to spread throughout the clinical world. Understanding that many of the
      infections that affect structures of the head and neck are actually biofilm
      related is fundamental to developing rational strategies for treatment and
      prevention.

PMID- 15167028
TI  - The endoscopic radiofrequency approach to management of GERD.
AB  - PURPOSE OF REVIEW: Endoscopic treatment has been recently introduced as a new
      option for treating gastroesophageal reflux disease. In this article the authors
      review the radiofrequency approach known as the Stretta procedure, as more
      evidence has linked reflux to upper airway disease. RECENT FINDINGS: Since 1968,
      when laryngeal disorders were linked to gastroesophageal reflux disease, more
      upper airway diseases such as chronic laryngitis, subglottic stenosis, and even
      laryngeal carcinoma were found to be occasionally caused by extraesophageal
      reflux. Most otolaryngologists treat these patients with proton pump inhibitors,
      which improve symptoms in two thirds of patients. Antireflux surgery remains the
      treatment of choice, relieving symptoms in more than 90% of patients. Endoscopic
      treatment has recently emerged as an option for treatment of gastroesophageal
      reflux disease. The Stretta procedure delivers radiofrequency energy to the
      gastroesophageal junction. This has proved to be effective in controlling reflux
      by inhibiting transient, inappropriate lower esophageal sphincter relaxation,
      increasing postprandial lower esophageal spincter pressure, and decreasing lower
      esophageal sphincter compliance. Stretta is among the earliest endoscopic
      technologies to be approved by the Food and Drug Administration for the treatment
      of reflux. It has the longest term follow-up published to this date, and the most
      durable effect. It is performed under intravenous sedation on an outpatient basis
      and has a low incidence of complications. SUMMARY: The Stretta procedure is an
      endoscopic, noninvasive modality for the treatment of gastroesophageal reflux
      disease. It should be considered in the treatment of reflux-related upper airway
      diseases.

PMID- 15167029
TI  - Botulinum toxin and the management of chronic headaches.
AB  - PURPOSE OF REVIEW: There is an increasing number of reports on botulinum toxin in
      pain therapy, in particular in headache treatment. Therefore, the studies
      available from reference systems and published congress contributions on the
      prophylactic treatment of idiopathic and cervicogenic headache with botulinum
      toxin were analyzed with respect to study design, headache diagnosis, and the
      significance of results. RECENT FINDINGS: For the prophylactic treatment of
      tension-type headache, migraine, and cervicogenic headache, no sufficient
      positive evidence for treatment with botulinum toxin is obtained from randomized,
      double-blind, placebo-controlled trials to date. For the treatment of
      miscellaneous headache, there is some but no consistent positive evidence.
      SUMMARY: Most open studies and case reports suggest an efficacy of botulinum
      toxin in headache prophylaxis but double-blind, placebo-controlled studies do not
      confirm this assumption. Larger controlled studies are needed for a definite
      evaluation of subgroups that might possibly benefit from such a treatment.
      Migraine, tension-type headache, and cervicogenic headache cannot be regarded as
      a general indication for a treatment with botulinum toxin.

PMID- 15167030
TI  - Surgical robotics in otolaryngology: expanding the technology envelope.
AB  - PURPOSE OF REVIEW: Surgical robotics arose as an extension of virtual reality and
      robotic technology developed by the United States Department of Defense. Current
      surgical robotic systems have been used to perform a variety of minimally
      invasive surgical procedures. RECENT FINDINGS: The Food and Drug Administration
      recently granted approval for the clinical use of two surgical robotic systems.
      Laboratory and clinical experience suggests that the use of surgical robotics is
      associated with some distinct advantages and disadvantages when compared with
      conventional open procedures. Robotic surgery has recently been described in the
      head and neck, and as a result the otolaryngologist should have a basic
      understanding of the potential applications of surgical robotics in head and neck
      surgery. SUMMARY: Surgical robotic technology is evolving but appears to have a
      distinct place in the surgical armamentarium.

PMID- 15167031
TI  - Contemporary trends in acute pain management.
AB  - PURPOSE OF REVIEW: In the management of acute pain, the ability to prevent the
      onset of pain in the immediate postoperative period, lessen its intensity, and
      interfere with the development of sensitization contributing to hyperalgesia for
      days following a procedure can greatly benefit the patient, rather than
      postoperative attempts to decrease pain after it has reached full intensity.
      RECENT FINDINGS: Patients benefit from receiving optimal NSAID doses. These
      agents are effective, relatively safe, and reduce the need for opioids. In
      situations where pain can be anticipated, the NSAID may be optimized by
      preoperative administration and continuing to dose the NSAID on a regular
      schedule to minimize pain and inflammation. Selective COX-2 inhibitors can also
      prevent pain but without concern for effects on platelet function and have a
      longer duration of action than traditional NSAIDs. Once the dose of NSAID has
      been optimized, but pain persists, opioid use may be a consideration. A
      commercially available combination product containing opioid and acetaminophen
      may be a good option and is easy to prescribe. Acetaminophen's site of action
      differs from that of NSAIDs, and acetaminophen's analgesic effect is considered
      synergistic when combined with NSAIDs and opioids. When prescribing combination
      opioid and acetaminophen analgesic products or acetaminophen alone, the
      practitioner must caution the patient not to exceed 4 g of acetaminophen per day
      due to concerns with hepatic injury. Given that the patient has already been
      prescribed an optimal and/or ceiling dose of NSAID, combination products
      containing aspirin, an NSAID, should be avoided. As opioids have no ceiling dose,
      there are some situations where opioid dosing is better done with the opioid
      prescribed separately. This permits increasing the opioid to the needed analgesic
      dose with no concerns for acetaminophen toxicity. SUMMARY: Careful selection of
      an effective analgesic regimen can prevent the stress and anxiety associated with
      acute postoperative pain and breakthrough pain. Pain prevention has greater
      benefits than attempts at rescue therapy when pain exacerbation occurs. A variety
      of pain management regimens are presented based on empirical estimates of pain
      intensity and an application of sound pharmacological principles.

PMID- 15167032
TI  - Special features topic: the effects of limited work hours on surgical training in
      otolaryngology-head and neck surgery.
AB  - PURPOSE OF REVIEW: This paper reviews the historic events that culminated in the
      development of duty hour regulations, and then discusses many of the problems
      being encountered as the regulations are implemented. RECENT FINDINGS: On July 3,
      2003, the Accreditation Council for Graduate Medical Education (ACGME) instituted
      duty hour requirements for residency training programs in the United States.
      Although these regulations should have come as no surprise to graduate medical
      education programs, many were nevertheless unprepared for their implementation.
      In comparison to duty hour restrictions currently in place in European countries,
      those being implemented in this country are much more lenient. Both the fiscal
      and the educational impact of these requirements on graduate medical education
      are substantial. Recent accreditation actions taken against a training program at
      Johns Hopkins University clearly demonstrates that the ACGME is prepared to
      strictly enforce these standards. SUMMARY: The impact of the new duty-hour
      requirements on residency training and education will be a matter of great
      interest as they are implemented throughout the graduate education system in the
      United States.

PMID- 15167033
TI  - The immune response in "allergy".

PMID- 15167034
TI  - Vaccination and allergy.
AB  - PURPOSE OF REVIEW: Vaccines have had a major effect on controlling the spread of
      infectious diseases, but use of certain vaccines was linked to potential allergic
      and autoimmune side effects in healthy and often in certain high-risk
      populations. In this review the authors summarize the current knowledge of such
      risks. RECENT FINDINGS: Immediate systemic allergic reactions after vaccination
      with commonly used vaccines are extremely rare. Use of certain vaccines was
      linked to potential allergic side effects in healthy and often in certain high
      risk populations. The authors review the data on the risk associated with
      important vaccines including influenza, smallpox, pneumococcus, Japanese
      encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and
      rubella. Two main components were identified as a source for allergic reactions
      in vaccines: gelatin and egg protein. There is growing interest in the potential
      interactions between infant vaccination and risk for development of atopic
      disease. In addition, there is concern that genetic risk for atopy influences
      capacity to respond to vaccination during infancy. There is no evidence that
      vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps,
      and rubella; or smallpox have an effect on the risk of the development of atopy
      later in life. Immunotherapy provides an efficacious and safe method for the
      treatment of allergic conditions by immunomodulation of the immune system. The
      possibility of vaccination triggering or unmasking autoimmunity in genetically
      susceptible individuals cannot be ruled out, but for the general population the
      risk-to-benefit ratio is overwhelmingly in favor of vaccinations. SUMMARY:
      Childhood vaccination remains an essential part of child health programs and
      should not be withheld, even from children predisposed to allergy. Vaccinations
      are safe, but special attention should be taken in high-risk individuals with
      anaphylactic reactions to foods, and in patients with autoimmune diseases.

PMID- 15167035
TI  - The hygiene theory: fact or fiction?
AB  - PURPOSE OF REVIEW: The "hygiene hypothesis" offers a potentially credible and
      parsimonious explanation for the increasing prevalence of allergy noted in many
      westernized populations. The authors review recent evidence both for and against
      this hypothesis. RECENT FINDINGS: A strong body of epidemiologic evidence
      indicates that the original observations, namely of a birth order effect and
      increased risk of atopic disorders in those born into small, affluent households,
      are robust findings. Improved hygiene is believed to mediate its effect through
      decreased exposure to infectious agents in early life, and recent evidence has
      focused attention on the importance of the gastrointestinal microbial
      environment. In particular, infection with hepatitis A, Helicobacter pylori, and
      toxoplasma in those living in temperate climates, and geoheminths in those living
      in endemic areas, have been shown to be associated with reduced risk of atopic
      manifestations. It is postulated that these infections exert their effect through
      critically altering T-helper (Th)1/Th2 regulation, which is supported by the
      examination of the cytokine profiles of cord mononuclear cells when exposed to
      gastrointestinal flora and, furthermore, emerging evidence on the benefits of
      probiotics on symptoms of atopic dermatitis. Attempts to identify an inverse
      relation between Th1- and Th2-mediated disorders (as might be predicted by the
      Th1/Th2 paradigm) have, however, yielded conflicting results, raising the
      possibility that this model may be something of an oversimplification. SUMMARY:
      The hygiene hypothesis remains a credible but nonspecific explanation for
      observed variations over time, place and persons at risk for developing atopic
      allergic disorders. More prospective studies are needed to unravel which
      infectious agents exert a protective effect and the time period of importance for
      sensitization. The clinical implications of these advances in our understanding
      of the etiology of atopic allergic disorders are currently limited.

PMID- 15167036
TI  - Categorization of eosinophilic chronic rhinosinusitis.
AB  - PURPOSE OF REVIEW: The presence of eosinophilia histopathologically in sinusitis
      is frequently associated with greater disease objectively and a decreased
      likelihood of surgical success. Eosinophilic chronic rhinosinusitis encompasses a
      wide variety of etiologies and associations that can be grouped under this
      umbrella term. In addition, this term can be further divided into those patients
      with no polyps and those with polyps. The purpose of this review is to detail the
      epidemiology of eosinophilic chronic rhinosinusitis, to define known and
      potential subcategories, and to discuss targeted therapeutic interventions.
      Eosinophilia is frequently, but not exclusively, caused by IgE-mediated
      hypersensitivity and is dominated by the associated cytokine milieu of Th2
      inflammation. Thus, allergic rhinitis or allergy is a subcategory and not
      synonymous with eosinophilic chronic rhinosinusitis. RECENT FINDINGS: Recent
      findings supporting mechanisms that promote eosinophilic infiltration are
      discussed and include the following subcategories: super antigen-induced
      eosinophilic chronic rhinosinusitis, allergic fungal sinusitis, nonallergic
      fungal eosinophilic chronic rhinosinusitis, and aspirin-exacerbated eosinophilic
      chronic rhinosinusitis. Undoubtedly there are other mechanisms and
      categorizations of eosinophilic chronic rhinosinusitis as yet unknown. It is
      possible, and in fact probable, that some patients may have overlapping
      mechanisms for eosinophilia. Corticosteroid therapy is an important treatment
      across all eosinophilic disorders and a profoundly potent but nonspecific
      antiinflammatory agent. Within each subcategory a specific antibacterial,
      antifungal, or immune modulation may be indicated. SUMMARY: The subcategories of
      eosinophilic chronic rhinosinusitis are discussed in light of recent findings and
      treatment recommendations.

PMID- 15167038
TI  - Bibliography. Current world literature. Speech therapy and rehabilitation.

PMID- 15167037
TI  - Vasomotor rhinitis update.
AB  - PURPOSE OF REVIEW: This review was conducted to examine new data on vasomotor
      rhinitis, a common clinical problem. RECENT FINDINGS: Recent publications
      highlight advances in the study of the pathophysiology of vasomotor rhinitis.
      Electron microscopic and ultracytochemical evaluation of the nasal mucosa in
      vasomotor rhinitis demonstrates an emerging role of neuropeptides and nitric
      oxide in the pathogenesis of vasomotor rhinitis. Ozone, cigarette smoke, and
      other environmental factors may trigger neurogenic mechanisms that lead to
      vasomotor rhinitis. Objective tests have documented the presence of hypoactive
      sympathetic autonomic dysfunction. Such assessments also suggest autonomic
      dysfunction as a possible link between vasomotor rhinitis and gastroesophageal
      reflux disease. Recent publications propose nasal secretory protein analysis as a
      possible diagnostic tool. Evidence-based review of treatment outcomes shows
      topical sprays of azelastine, budesonide, and ipratropium to be of benefit in
      vasomotor rhinitis. SUMMARY: A better understanding of the role of nitric oxide
      and neuropeptides in the pathogenesis of vasomotor rhinitis has opened new
      avenues in research, diagnosis, and management. Clinical diagnosis may be aided
      by the analysis of nasal secretory proteins. Effective treatments include
      antihistamine, anticholinergics, and steroid nasal sprays.

PMID- 15167039
TI  - Pleomorphic salivary adenoma of the parotid gland: which operation to perform?

PMID- 15167040
TI  - Medical malpractice and head and neck cancer.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate medical malpractice
      involving patients with head and neck cancer. In the United States, problems
      associated with the medical malpractice environment are reaching proportions that
      threaten the delivery of health care. RECENT FINDINGS: Several methods to learn
      more about the trends and ramifications of litigation have been developed.
      Although patients with cancer of the head and neck bring suits rarely, when they
      do several themes seem prevalent. Delays in diagnosis are common allegations.
      Plaintiffs are frequently much younger than expected, and the oncologic outcome
      is frequently poor. Defendant physicians occasionally unwittingly add to the
      delay by not expecting the younger patient. The poor oncologic outcome may be
      related to the delay or to a biologically more aggressive disease. Relationships
      between these factors are explored. Consent issues are also relatively common.
      SUMMARY: Physicians must strive to know as much as possible about tort reform,
      and to contribute to the process. Litigation analysis and other tools to expand
      our understanding can be used to educate ourselves and the legal community.
      Scientific standards must be developed along with clinical pathways to guide
      ourselves to prevent litigation. They may also guide the legal community to
      establish more rational standards of care based on a consensus of expert
      opinions.

PMID- 15167041
TI  - Cancers presenting in the head and neck during pregnancy.
AB  - PURPOSE OF REVIEW: The purpose of this review is to document the information
      reported on cancers presenting in the head and neck area during pregnancy. RECENT
      FINDINGS: Accidents and cancer account for most deaths during the reproductive
      years. Cancer complicates approximately 0.1% of all pregnancies and, in order of
      frequency, the incidence of cancers by site are breast, melanoma, thyroid,
      cervix, lymphoma, and ovary. Some of these cancers may present in the head and
      neck region, as well as more uncommon cancers such as mucosal squamous cell
      carcinoma. SUMMARY: It is recognized that with the dramatic rise in births among
      "reproductively" older women and with the changing epidemiology of squamous cell
      carcinoma of the head and neck in nonsmoking and nonalcohol-drinking women, there
      is to be expected an increased incidence and presentation. Management of such
      patients must consider the gestational age of the pregnancy and must include
      alternatives to current treatments to accommodate the individual's wishes
      regarding her pregnancy.

PMID- 15167042
TI  - Current thoughts on the role of chemotherapy and radiation in advanced head and
      neck cancer.
AB  - PURPOSE OF REVIEW: The management of advanced malignancies of the head and neck
      continues to be a challenging clinical problem. During the last three decades,
      the traditional treatments of surgery and/or radiation have not yielded
      significant improvements in survival in this patient population. In addition,
      surgery for advanced disease can create significant functional and cosmetic
      defects that adversely impact a patient's quality of life. Newer "organ
      preservation" approaches using chemotherapy and radiation are currently being
      studied in an attempt to improve survival while maintaining the functional
      integrity of the disease site. RECENT FINDINGS: Recent studies have demonstrated
      that for advanced head and neck squamous cell cancers, concurrent chemoradiation
      is superior to radiation alone for local tumor control and perhaps overall
      survival. With the exception of laryngeal cancer, phase III data comparing
      chemoradiation with surgery is lacking for most head and neck subsites. However,
      comparisons with historical controls suggest that chemoradiation strategies may
      offer improved outcomes when compared with more traditional treatment regimens.
      SUMMARY: This review emphasizes recent phase III trials that support the use of
      chemoradiation strategies in the treatment of advanced head and neck squamous
      cell cancers.

PMID- 15167043
TI  - Human papillomavirus infection in the etiology of laryngeal carcinoma.
AB  - PURPOSE OF REVIEW: One fifth of cancers worldwide are associated with viral
      infection. Indeed, the causal link between human papillomavirus and cervical
      carcinoma is so well established that it is thought to be the first necessary
      cause of human cancer ever identified. One of the primary aims of research in
      this area is to reduce cancer prevalence by vaccination. However, the role that
      human papillomavirus plays in carcinogenesis of the head and neck region may also
      have important implications for its prevention and treatment. RECENT FINDINGS:
      Although human papillomavirus was first identified in the larynx 20 years ago,
      the extent to which it is present in epithelium of the normal population is
      unclear. Laryngeal papillomas are the most common benign tumors in the larynx.
      They are associated with a small risk (3 to 7%) of malignant transformation, in
      which smoking and irradiation appear to be cofactors. The search for alternate
      risk factors for the development of laryngeal cancer, particularly in those who
      are nonsmokers and nondrinkers, has led to the hypothesis that human
      papillomavirus may have a pivotal role. Epidemiologic studies, although not
      conclusive, strongly suggest its involvement in the etiology of a subset of
      laryngeal carcinomas. Recent molecular evidence supports this. SUMMARY: An
      adequately powered, multicenter case-control study is required to elucidate the
      full extent of this association and to examine the relation between the virus and
      other risk factors.

PMID- 15167044
TI  - The management of parathyroid carcinoma.
AB  - PURPOSE OF REVIEW: To summarize the current treatment approaches to parathyroid
      malignancy. RECENT FINDINGS: Recent advances in molecular biology are aiding the
      understanding of the pathogenesis of this condition, and imaging modalities are
      contributing to localization of the abnormal parathyroid tissue. SUMMARY: The
      treatment of parathyroid malignancy is overwhelmingly surgical, comprising an
      initial en bloc resection of the tumor and adjacent structures. The risk of tumor
      recurrence is high and may require several metastasis resections in order to
      control symptoms of hypercalcemia.

PMID- 15167045
TI  - Chondroma and chondrosarcoma of the larynx.
AB  - PURPOSE OF REVIEW: The purpose of this review is to give a detailed description
      of chondroma and chondrosarcoma of the larynx and to put into perspective new
      findings from recent literature. RECENT FINDINGS: Recent findings indicate that
      chondroma and chondrosarcoma of the larynx are closely related, either
      synchronously (areas of both tumor types within the same lesion) or
      metachronously (malignant transformation of chondroma over time). It is
      questioned whether the grading of Lichtenstein and Jaffe, and Evans et al. should
      be used in the larynx, because these grading systems were designed for
      chondrosarcoma of the long bones. Chondrosarcomas of the larynx seems to behave
      more like chondrosarcomas of the phalanx, because they too hardly ever
      metastasize or cause tumor-related deaths. Both CT and MRI play an important role
      in the workup of these tumors, but they cannot be used to differentiate between
      both tumor types. No new treatment modalities have emerged recently and surgery
      is still the treatment of choice. Tracheal autotransplantation may play an
      increasing role in the treatment of cricoid tumors because it allows for wide
      resection and optimal revalidation. SUMMARY: It is now firmly established that
      metastasis in chondrosarcoma is a poor prognostic sign, but is very rare. Without
      metastasis the prognosis is excellent. Cartilaginous tumors of the larynx are
      rare. Clinical, radiologic and pathologic characteristics of these tumors are
      described and a review of treatment modalities is presented. Wide excision with
      clear margins is usually indicated. The authors recommend that the management of
      cartilaginous tumors of the larynx be multidisciplinary and centralized in
      dedicated referral centers.

PMID- 15167046
TI  - Thyroglossal duct carcinoma.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review the presentation and
      management of thyroglossal duct carcinoma. RECENT FINDINGS: Recent articles have
      analyzed the value of preoperative investigation and have addressed some of the
      controversies in the management of such tumors; in particular, the optimal
      surgical management of the thyroid gland, as well as optimal management of lymph
      node metastases, the role of thyroid suppression therapy, and radioactive iodine
      therapy. SUMMARY: Thyroglossal duct carcinoma is uncommon, occurring in
      approximately 1% of all thyroglossal duct cysts. It is often diagnosed
      incidentally after surgical excision. Ninety-four percent of carcinomas are of
      thyroid origin, with most being papillary in nature, and 6% are of squamous cell
      origin. Incidentally discovered, well-differentiated thyroid carcinoma of the
      thyroglossal duct, in the presence of a clinically and radiologically normal
      thyroid gland, can be managed adequately by the Sistrunk operation. Those
      patients with more advanced disease require more aggressive treatment. This may
      include a total thyroidectomy with or without neck dissection in addition to the
      Sistrunk operation, followed by radioactive iodine therapy and thyroid
      stimulating hormone suppression. The prognosis is generally excellent with
      adequately treated disease.

PMID- 15167048
TI  - Basaloid squamous cell carcinoma of the head and neck.
AB  - PURPOSE OF REVIEW: Basaloid squamous cell carcinoma is an uncommon variant of
      squamous cell carcinoma and was first described as a distinct entity in 1986.
      Basaloid squamous cell carcinoma seems to have a poorer survival rate than
      classical squamous cell carcinoma. On the basis of a critical literature survey,
      we attempt to evaluate if basaloid squamous cell carcinoma is really more
      aggressive and presents a poorer outcome than squamous cell carcinoma. RECENT
      FINDINGS: All papers are retrospective, and most include small numbers of cases,
      which are further diminished when subdivided according to specific sites. Only in
      three studies was basaloid squamous cell carcinoma of the head and neck region
      compared with matched squamous cell carcinoma controls. These studies did not
      show a uniform tendency regarding the aggressiveness and outcome of basaloid
      squamous cell carcinoma. In addition, several recent papers confirmed the
      presumed greater aggressiveness and worse outcome, and other recent papers
      questioned these characteristics. SUMMARY: The presented literature survey does
      not permit conclusions regarding the aggressiveness and outcome of basaloid
      squamous cell carcinoma compared with squamous cell carcinoma. Greater numbers of
      basaloid squamous cell carcinoma should be studied and compared with site
      matched, stage-matched, and age-matched controls of conventional squamous cell
      carcinoma.

PMID- 15167047
TI  - Contemporary management of carotid blowout.
AB  - PURPOSE OF REVIEW: The purpose of this report is to summarize existing literature
      with respect to carotid artery blowout and to present an up-to-date algorithm for
      its management that incorporates recent advances with respect to its diagnosis
      and treatment. RECENT FINDINGS: Although once thought as one entity, carotid
      blowout is now considered to be a syndrome with clinical manifestations ranging
      from acute hemorrhage to asymptomatic exposure of a carotid artery. As a result,
      carotid blowout syndrome can present as one of three separate entities:
      threatened, impending, and acute carotid blowout. In recent years newer
      approaches to management have centered around the use of diagnostic angiography
      followed by definitive therapy with either carotid occlusion by coils, detachable
      balloons, or endovascular stents. Overall morbidity of management has decreased.
      SUMMARY: Interventional radiologic techniques have revolutionized the treatment
      of carotid blowout syndrome, allowing more accurate diagnosis and lower treatment
      morbidity.

PMID- 15167049
TI  - Head and neck cancer in transplant recipients.
AB  - PURPOSE OF REVIEW: Transplant recipients have an increased incidence of cancer
      compared with the general population. Head and neck sites are involved in more
      than 50% of patients, and as a result the otolaryngologist should be familiar
      with the diagnosis and management of posttransplant malignancies. RECENT
      FINDINGS: Skin cancer is the most common malignancy encountered in the transplant
      population, and in areas of high sun exposure, as many as 80% of patients are
      affected. Patients who undergo liver transplantation for alcoholic cirrhosis
      appear to be at particularly increased risk for developing posttransplant
      malignancy of the head and neck. A number of uncommon malignancies such as
      Kaposi's sarcoma occur with a greatly increased incidence in transplant
      recipients. Malignancy in this patient population tends to present at a younger
      age compared with the general population, with a more aggressive course and
      poorer outcomes reported. SUMMARY: A high index of suspicion may reduce morbidity
      and mortality through early detection of malignant disease in the transplant
      recipient.

PMID- 15167051
TI  - The facial nerve in the presence of a head and neck neoplasm: assessment and
      outcome after surgical management.
AB  - PURPOSE OF REVIEW: The face is the mirror of personality. Facial expression is
      the most important part of verbal and nonverbal communication. Patients with head
      and neck neoplasm and facial palsy are more stigmatized by the latter than by the
      tumor itself. Facial nerve reconstruction in such a patient is a great challenge.
      This review gives an overview of the assessment of facial palsy, surgical
      reconstruction, and postoperative treatment. RECENT FINDINGS: MRI, CT, and
      electromyography are indispensable tools in the assessment of preoperative facial
      palsy in patients with head and neck neoplasm. When part of the facial nerve has
      to be sacrificed during surgery, the best functional results are achieved with
      direct facial nerve suture, interposition graft, or by a hypoglossal-facial nerve
      interposition jump anastomosis. The latter is the best choice when the
      reanimation is planned between 6 months and 2 years after tumor surgery. In any
      case, the eye is best rehabilitated with upper lid loading. Temporalis muscle
      transposition gives fast and good results for the restoration of the corner of
      the mouth after radical surgery. Reanimation by free muscle transfer for head and
      neck cancer patients is rarely indicated. Botulinum toxin treatment is an
      excellent postoperative aid for refining the result; the optimal modality of
      postoperative physiotherapy is still unclear. SUMMARY: Surgical reanimation of
      the face in head and neck patients has reached a high standard. Strategies to
      decrease misdirected reinnervation after nerve suture have to be established in
      clinical practice for further improvement of facial rehabilitation.

PMID- 15167050
TI  - Adenoid cystic carcinoma of the head and neck: a review.
AB  - PURPOSE OF REVIEW: This purpose of this article is to review and provide an
      update of current publications on the evaluation and management of adenoid cystic
      carcinoma. RECENT FINDINGS: Adenoid cystic carcinoma is an uncommon salivary
      gland malignancy that presents insidiously and is generally advanced when
      diagnosed. Current effective treatment modalities include surgery and
      irradiation, but locoregional recurrences are frequent and may present as early
      as 2 years. Patients survive with recurrent and metastatic disease for several
      years despite not being offered any treatment. Molecular analysis of the tumors
      is being undertaken, with optimistic results capable of selecting high-risk
      patients who may benefit from adjuvant treatment such as chemotherapy SUMMARY:
      Little progress has been made in advancing "curative" treatment of adenoid cystic
      carcinoma of the head and neck. The disease is said to have a fatal outcome. The
      time is now opportune for a multicenter, randomized, controlled trial to identify
      patients who would benefit from adjuvant radiotherapy and/or chemotherapy in the
      control of locoregional recurrences and the prevention of distant metastases.

PMID- 15167052
TI  - On completion of curative treatment of head and neck cancer: why follow up?
AB  - PURPOSE OF REVIEW: To review the rationale and evidence for maintaining clinical
      contact with patients who have received curative treatment for head and neck
      cancer. RECENT FINDINGS: Very little work has been published in the scientific
      literature on this subject. Most information regarding follow-up care has focused
      on survival outcomes rather than the rationale for, or cost-effectiveness of,
      routine surveillance of head and neck cancer patients. Perhaps this is because
      there seems to be very little controversy. A large survey of surgeons has
      revealed a diminishing frequency of follow-up with time after treatment, although
      with variance in respect of specific investigations such as bone scans.
      Notwithstanding the current paper identifies areas that need to be considered
      when decisions are made regarding the scheduling of follow-up appointments
      SUMMARY: Regular post-treatment surveillance is important for patients' general
      well-being and for the management of late complications of treatment in long-term
      survivors. It is unclear whether surveillance provides any survival advantage;
      this information requires the sort of clinical trial that has been conducted for
      tumors at other sites, such as colorectal cancer and breast cancer, but not head
      and neck cancers.

PMID- 15167053
TI  - Bibliography. Current world literature. Head and neck oncology.

PMID- 15167056
TI  - Neutralizing antibodies to interferon beta: implications for the management of
      multiple sclerosis.
AB  - PURPOSE OF REVIEW: Antibodies against interferon-beta (IFN-beta) can appear in a
      relevant number of patients. The subset of antibodies that can neutralize IFN
      beta activity are called neutralizing antibodies. This review focuses on their
      impact both on therapeutic efficacy and on bioactivity of IFN-beta, and on the
      management of antibody-positive patients. RECENT FINDINGS: When IFN-betas were
      first used, neutralizing antibodies were not considered important. However,
      recent clinical, biologic, and immunologic data have demonstrated that they
      reduce or abolish the therapeutic efficacy of IFN-beta in 10-20% of patients.
      Quantification of antibodies using various biologic methods make it difficult to
      compare among different laboratories, and hence, standardization of assay
      procedures is necessary. Despite these technical difficulties, data consistently
      show differences in immunogenicity among the different IFN-beta products and the
      negative effects of neutralizing antibodies on the clinical efficacy of IFN
      betas. Because the therapeutic action of IFN-beta depends on activation of IFN
      inducible genes, new methods for the quantification of the biologic activity of
      IFN-beta have been developed, and a good correlation has been found between the
      presence of neutralizing antibodies and abrogation of IFN-beta bioactivity.
      SUMMARY: Quantification of neutralizing antibodies and the in-vivo bioactivity of
      IFN-beta through IFN-beta-inducible gene products such as Myxovirus protein A,
      offer valuable information on IFN-beta therapy. Important questions such as the
      optimal therapeutic strategy for managing neutralizing antibodies positive
      patients require further study in clinical trials.

PMID- 15167057
TI  - Cell-based remyelinating therapies in multiple sclerosis: evidence from
      experimental studies.
AB  - PURPOSE OF REVIEW: Spontaneous remyelination occurs in the central nervous system
      of patients with multiple sclerosis. However, this process is not robust enough
      to promote a functional and stable recovery of the myelin architecture. The
      development of cell-based therapies, aimed at promoting multifocal remyelination,
      is therefore foreseen. RECENT FINDINGS: Several experimental cell-based
      strategies aimed at replacing damaged myelin-forming cells have been developed in
      the last few years. However, most of these therapeutic approaches - although
      consistently able to form new myelin sheaths at the transplantation site - are
      unfeasible owing to the mutifocality of the demyelinating process in multiple
      sclerosis patients and the inability to grow and produce large numbers of
      differentiated myelin-forming cells in vitro. Stem cell-based therapies that
      partially overcome these limitations have been proposed recently. SUMMARY: Stem
      cell-based remyelinating therapies can be considered a plausible alternative
      strategy in immune-mediated demyelinating disorders. However, before any
      potential applications in patients with multiple sclerosis can be envisaged, it
      is necessary to confront the following preliminary, and still unsolved,
      questions: (1) the ideal stem cell source for transplantation; (2) the most
      appropriate route of stem cell administration; and, last but not least, (3) the
      best approach for achieving an appropriate, functional and long-lasting
      integration of transplanted stem cells into the host tissue.

PMID- 15167058
TI  - Health outcomes in multiple sclerosis.
AB  - PURPOSE OF REVIEW: Economic considerations are increasingly important in the
      evaluation of innovative medical technologies. In the past few years, evaluations
      of cost and cost-effectiveness analysis became a popular topic for multiple
      sclerosis research. Here, we review cost-of-illness and cost-utility studies in
      multiple sclerosis published during the past 2 years. RECENT FINDINGS: Despite
      differences in methodology, several cost-of-illness studies unequivocally
      demonstrated that indirect costs as a result of sick leave, premature retirement
      or loss of income made up almost half of the overall costs, and that total costs
      were higher in the more advanced stages of the disease. Cost-effectiveness
      studies of recombinant IFN-beta preparations demonstrated a marked variability in
      the incremental cost per quality-adjusted life-year, with amounts ranging from
      Euro 28 432 to US$338 738. For glatiramer acetate and mitoxantrone, only limited
      data are available, but even these few studies differed in their results.
      SUMMARY: Health outcome studies constitute a new and emerging field of multiple
      sclerosis research. All studies performed so far underscore the importance of
      indirect cost in multiple sclerosis. However, the marked differences in cost
      effectiveness studies illustrate that the method of economic modeling has
      considerable impact on the results of these studies, which need standardization
      in order to evaluate properly the economic consequences of new and expensive
      therapies in multiple sclerosis.

PMID- 15167059
TI  - Progress in X-linked adrenoleukodystrophy.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review and evaluate the new
      information about X-linked adrenoleukodystrophy that has been reported in 2002
      and 2003. RECENT FINDINGS: X-linked adrenoleukodystrophy has two distinct
      neurological phenotypes: adrenomyeloneuropathy, a non-inflammatory axonopathy
      mostly in adults, and an intensely inflammatory cerebral myelinopathy mostly in
      children. The two forms often co-occur in the same family. Heterozygous women and
      the X-linked adrenoleukodystrophy mouse model often have the
      adrenomyeloneuropathy phenotype. More than 500 distinct mutations in the
      defective gene (ABCD1) have been identified, and except in one unique family, do
      not correlate with the phenotype. Bone marrow transplantation is beneficial in
      patients with early cerebral involvement. A panel of brain neuroimaging studies
      aids the selection of patients for bone marrow transplantation. Lorenzo's oil
      administered to neurologically asymptomatic boys who are less than 6 years old
      and have a normal magnetic resonance imaging scan appears to reduce the
      probability of developing neurological abnormalities later in life. SUMMARY:
      Progress has been achieved in the delineation of the phenotypes, pathogenesis,
      diagnosis and prevention of X-linked adrenoleukodystrophy, and therapies are
      emerging.

PMID- 15167060
TI  - Advances in the field of headache 2003/2004.

PMID- 15167061
TI  - Headache classification update 2004.

PMID- 15167062
TI  - Recent findings in headache genetics.
AB  - PURPOSE OF REVIEW: The progress in headache genetics, especially migraine
      genetics, recently jumped ahead with some major discoveries. RECENT FINDINGS:
      Family and epidemiological studies further strengthen the genetic contribution to
      migraine and two recent observations gave new molecular insights in the disease.
      Studies on the genetics of familial hemiplegic migraine revealed, in addition to
      the previously identified familial hemiplegic migraine type 1 gene CACNA1A on
      chromosome 19, the familial hemiplegic migraine type 2 gene ATP1A2, encoding the
      alpha2-subunit of sodium/potassium pumps. Recent genome screens in families with
      migraine identified susceptibility loci on chromosomes 4, 6, 11 and 14. SUMMARY:
      The findings in familial hemiplegic migraine confirm that dysfunction in ion
      transport is a key factor in migraine pathophysiology and might help us in the
      elucidation of migraine molecular pathways. The identification of several
      migraine susceptibility loci underline its genetically complex nature.

PMID- 15167063
TI  - Migraine aura: new information on underlying mechanisms.
AB  - PURPOSE OF REVIEW: Since the initial description of cortical spreading depression
      by Leao, evidence that cortical spreading depression is the underlying
      pathomechanism of migraine aura has increased. The purpose of this review is to
      describe the ultimate genetic and molecular mechanisms of migraine aura. RECENT
      FINDINGS: It has been debated how a primarily cortical phenomenon (aura phase)
      may activate trigeminal fibres (headache phase). Recent data have demonstrated a
      link between cortical events and activation of the pain-sensitive structures of
      the dura mater. The initial cortical hyperperfusion in cortical spreading
      depression is partly mediated by the release of trigeminal and parasympathetic
      neurotransmitters from perivascular nerve fibres, whereas delayed meningeal blood
      flow increase is mediated by a trigeminal-parasympathetic brainstem connection.
      With regard to molecular mechanisms, cortical spreading depression upregulates a
      variety of genes coding for COX-2, TNF-alpha and IL-1beta, galanin or
      metalloproteinases. The activation of metalloproteinases leads to leakage of the
      blood-brain barrier, allowing potassium, nitric oxide, adenosine and other
      products released by cortical spreading depression to reach and sensitize the
      dural perivascular trigeminal afferents. In familial hemiplegic migraine, new
      mutations have been described in chromosome 1q23, leading to a haploinsufficiency
      of the sodium/potassium pump, producing an increase in intracellular calcium,
      similar to the CACNA1A mutation. SUMMARY: Recent studies have helped unravel the
      basic mechanisms involved in migraine aura. Far from being a simple phenomenon, a
      sequence of events leads from the cortex to the activation of pain-sensitive
      structures. The role of the brainstem is still poorly described. The
      identification of target molecules may provide new therapies.

PMID- 15167064
TI  - Rare nocturnal headaches.
AB  - PURPOSE OF REVIEW: This review describes rare headaches that can occur at night
      or during sleep, with a focus on cluster headaches, paroxysmal hemicrania, short
      lasting unilateral neuralgiform headache attacks with conjunctival injection and
      tearing, hypnic headache and exploding head syndrome. RECENT FINDINGS: It is
      known that cluster headaches and hypnic headache are associated with rapid eye
      movement sleep, as illustrated by recent polysomnographic studies. Functional
      imaging studies have documented hypothalamic activation that is likely to be of
      relevance to circadian rhythms. These headache syndromes have been shown to
      respond to melatonin and lithium therapy, both of which have an indirect impact
      on the sleep-wake cycle. SUMMARY: There is growing evidence that cluster headache
      and hypnic headache are chronobiological disorders.

PMID- 15167065
TI  - Medication overuse headache.
AB  - PURPOSE OF REVIEW: The current literature on medication overuse headache will be
      reviewed with regard to clinical presentation, pathophysiology, therapy and
      prognosis in the light of the new headache classification. RECENT FINDINGS:
      Medication overuse headache is a widely unrecognized medical condition, which
      according to recent epidemiological studies has evolved to the third most
      frequent form of headache after tension-type headache and migraine. The first
      classification of headache disorders from 1988 defined medication overuse
      headache (formerly called 'drug-induced headache') on the bases of drugs that
      were available in the 1980s. For the most important anti-headache drugs,
      including triptans, new data on specific clinical features and more important
      mean critical monthly dosages and mean critical monthly intake frequencies are
      now available. Furthermore, recent prospectively conducted studies have revealed
      rates and predictors of relapse after successful withdrawal. SUMMARY: The newly
      available data on medication overuse headache may provide the basis for future
      consensus guidelines for the management of this condition.

PMID- 15167066
TI  - Inflammation and neurological disease.

PMID- 15167067
TI  - Neurological complications of sarcoidosis.
AB  - PURPOSE OF REVIEW: The neurological manifestations of sarcoidosis, which occur in
      5% of patients with the condition, present in a variety of ways that can be
      assigned to several broad categories. A comprehensive approach to the diagnosis
      and management of neurosarcoidosis involves an appreciation of the strategies to
      confirm a diagnosis of sarcoidosis and neurosarcoidosis and the available
      therapeutic options. RECENT FINDINGS: In addition to traditional approaches to
      the diagnosis of sarcoidosis, positron emission tomography can be used to
      identify otherwise occult sites of systemic inflammation which can be targeted
      for biopsy. Although corticosteroids remain the mainstay of treatment, other
      immunosuppressive and immunomodulatory agents can be used in the multi-modality
      therapy of sarcoidosis. SUMMARY: Neurosarcoidosis can be 'staged' with the use of
      neurodiagnostic testing and diagnosed with varying degrees of certainty.
      Treatment should be approached within the context of the anticipated clinical
      course of the patient, avoidance of adverse drug effects, and, as necessary, from
      the perspective of the comprehensive management of a chronic disease.

PMID- 15167068
TI  - Vasculitis of the nervous system.
AB  - PURPOSE OF REVIEW: Vasculitis refers to heterogeneous clinicopathologic disorders
      that share the histopathology of inflammation of blood vessels. When unrecognized
      and therefore untreated, vasculitis of the nervous system leads to pervasive
      injury and disability making this a disorder of paramount importance to all
      clinicians. RECENT FINDINGS: Remarkable progress has been made in the
      pathogenesis, diagnosis, and treatment of vasculitis of the central (CNS) and
      peripheral nervous system (PNS). The classification of vasculitis affecting the
      nervous system includes (1) Systemic vasculitis disorders (necrotizing arteritis
      of the polyarteritis type, hypersensitivity vasculitis, systemic granulomatous
      vasculitis, giant cell arteritis, diverse connective tissue disorders; viral,
      spirochete, fungal, and retroviral infection; (2) Paraneoplastic disorders; (3)
      Amphetamine abuse; (4) Granulomatous angiitis of the brain; (5) Isolated
      peripheral nerve vasculitis, each in the absence of systemic involvement; and (6)
      diabetes mellitus, associated wtih inflammatory PNS vasculopathy. SUMMARY:
      Vasculitis is diagnosed with assurance after intensive evaluation. Successful
      treatment follows ascertainment of the specific vasculitic disorder and the
      underlying cytochemical mechanism of pathogenesis. Clinicians must choose from
      among the available immunomodulating, immunosuppressive, and targeted
      immunotherapies, unfortunately without the benefit of prospective clinical
      trials, tempered by the recognition of all of the possible medication related
      side effects.

PMID- 15167069
TI  - Recent advances in prion biology.
AB  - PURPOSE OF REVIEW: Prion diseases continue to present a diagnostic and
      therapeutic challenge to clinicians and researchers worldwide. Many important
      aspects of prion biology remain unclear, and we still do not understand the
      nature of the infectious agent, the mechanisms leading to central nervous system
      damage, and the physiological function of the cellular prion protein. The current
      diagnostic tools for prion infections are breathtakingly insensitive when
      compared with those of other infectious diseases. Finally, there are hardly any
      therapeutic strategies. However, not all is gloomy, and many recent developments
      have advanced our basic understanding of prion diseases. RECENT FINDINGS: In most
      prion infections, the portal of entry is extraneural. Although we still do not
      understand all details, several molecules and cell types have been identified as
      key players in prion neuroinvasion. These include lymphotoxins and their
      receptors, follicular dendritic cells, and the autonomic nervous system. These
      advances in knowledge are spurring the exploration of strategies for postexposure
      prophylaxis. SUMMARY: The prion phenomenon is, at the same time, the cause of
      horrible diseases, and a fascinating biological enigma. The scope of this review
      is to discuss a selection of novel findings in prion research.

PMID- 15167070
TI  - West Nile encephalitis and myelitis.
AB  - PURPOSE OF REVIEW: This article will review the recent experience with West Nile
      virus encephalitis and myelitis. RECENT FINDINGS: In the summer of 2003, the
      majority of cases of West Nile virus infection in the United States were reported
      from the western states. The transmission of West Nile virus through blood
      transfusion and organ transplantation was recognized and blood collection
      agencies implemented West Nile virus nucleic acid-amplification tests to identify
      infected donors. Intrauterine transmission of West Nile virus infection was
      reported. The identification of West Nile virus immunoglobulin M in cerebrospinal
      fluid is the recommended test to document central nervous system infection, but
      this test may not be positive in spinal fluid collected less than 8 days after
      the onset of symptoms. Serial samples of cerebrospinal fluid may be required to
      identify the antibodies. A clinical trial got underway to evaluate the efficacy
      of human immunoglobulin with high titers of antibodies to West Nile virus in the
      therapy of West Nile virus encephalitis and myelitis. SUMMARY: In the summer of
      2003, the majority of cases of West Nile virus infection in the United States
      were reported from states west of the Mississippi river. The identification of
      West Nile virus IgM in CSF is the recommended test to document CNS infection. A
      single serum antibody titer is an unreliable test of recent infection.

PMID- 15167071
TI  - Behcet's syndrome and the nervous system.
AB  - PURPOSE OF REVIEW: Behcet's syndrome (BS) is a multi-system, vascular
      inflammatory disease of unknown origin, involving the nervous system in a
      subgroup of patients. The syndrome is rare, but as patients with BS are young and
      frequently present with an acute or subacute brainstem syndrome or hemiparesis,
      as well as with other various neurological manifestations, the syndrome is often
      included in the differential diagnosis of multiple sclerosis, stroke of the young
      adult, and another wide range of neurological disorders. The present review
      summarizes the neurological involvement in BS, and emphasizes recent clinical
      concepts and ethiopathogenetic findings. RECENT FINDINGS: Over the last years the
      growing clinical and imaging evidence had suggested that neurological involvement
      in BS may be subclassified into two major forms: one, which is seen in the
      majority of patients, may be characterized as a vascular-inflammatory CNS
      disease, with focal or multifocal parenchymal involvement; the other, which has
      few symptoms and a better neurological prognosis, may be caused by isolated
      cerebral venous sinus thrombosis and intracranial hypertension. These two types
      rarely occur in the same individual, and their pathogenesis is likely to be
      different. A nonstructural vascular type headache is relatively common, whereas
      isolated behavioral syndromes and peripheral nervous system involvement are rare.
      SUMMARY: The involvement of the nervous system in BS is heterogeneous as clinical
      and imaging data reveal. Currently it is unknown which factors determine or have
      a role in the development of neurological involvement, but some progress has been
      achieved in understanding the neurological spectrum of the syndrome, which may
      lead to a better management of these patients.

PMID- 15167072
TI  - Uncertainties in the pathogenesis of adult dermatomyositis.
AB  - PURPOSE OF REVIEW: Dermatomyositis is an inflammatory disorder of muscle
      affecting both children and adults. The pathogenesis of adult dermatomyositis is
      reviewed here, with particular attention to gaps and uncertainties in our current
      understanding of this disease, in order to focus attention on the outstanding
      research questions with regard to disease mechanisms. RECENT FINDINGS: The
      conceptual model of the pathophysiology of dermatomyositis has been based on work
      extending back over at least 35 years, with important findings related to the
      deposition of membrane attack complex, the character of the inflammatory
      infiltrate, and the primacy of capillary abnormalities established over 10 years
      ago. The lack of significant additions to the understanding of this disease over
      the past few years suggests a state of contentment with current knowledge.
      Accordingly, we emphasize the uncertainties of this knowledge and the need for re
      addressing some of its basic tenets. SUMMARY: Although evidence remains strong
      that dermatomyositis is a disorder with an early involvement of the capillaries,
      the concept that it results from an antibody-mediated attack upon the endothelium
      is uncertain. It is not clear whether membrane attack complex is activated by
      antibody-dependent or independent means, whether or not intramuscular B cells are
      antigen specific and synthesize significant quantities of antibodies, whether the
      presence of tubuloreticular inclusions precedes, follows, or is independent of
      membrane attack complex deposition, what is the mechanism of perifascicular
      atrophy, and what is the relationship of dermatomyositis to systemic lupus
      erythematosus.

PMID- 15167073
TI  - New insights into progressive multifocal leukoencephalopathy.
AB  - PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy is a deadly
      demyelinating disease of the central nervous system, which occurs in
      immunosuppressed individuals. It is caused by a reactivation of the polyomavirus
      JC, which induces a lytic infection of oligodendrocytes. This review covers
      recent developments in the clinical and pathological presentations of progressive
      multifocal leukoencephalopathy, and advances in the understanding of JC virus
      biology. RECENT FINDINGS: The availability of highly active antiretroviral
      therapy has changed the clinical spectrum of progressive multifocal
      leukoencephalopathy in HIV-infected individuals; although the incidence has not
      diminished, mortality has decreased from 90% to approximately 50% during the
      first 3 months as a result of recovery of the immune system. More progressive
      multifocal leukoencephalopathy patients are now negative for JC virus in the
      cerebrospinal fluid by polymerase chain reaction, which calls for a new consensus
      terminology. Inflammatory forms of the disease are also becoming more frequent,
      and are associated with a strong cellular immune response mediated by JC virus
      specific CD8 cytotoxic T lymphocytes, which are instrumental in preventing
      disease progression. SUMMARY: Advances in the understanding of JC virus biology
      have shed new light on the pathogenesis of progressive multifocal
      leukoencephalopathy, and on its possible role in cerebellar atrophy in HIV
      infected individuals. Findings on the cellular immune response against the virus
      have direct implications for patient management, and may lead to new forms of
      immunotherapies for progressive multifocal leukoencephalopathy. An animal model
      of progressive multifocal leukoencephalopathy in non-human primates will
      facilitate the development of novel therapeutic strategies.

PMID- 15167074
TI  - Current world literature. Demyelinating diseases.

PMID- 15167077
TI  - Wild child.

PMID- 15167078
TI  - Wild child.

PMID- 15167080
TI  - Talking to families about ADHD.

PMID- 15167081
TI  - Evolution of a journal: outing some ghosts from the closet.

PMID- 15167082
TI  - An efficacy/effectiveness study of cognitive-behavioral treatment for adolescents
      with comorbid major depression and conduct disorder.
AB  - OBJECTIVE: To evaluate effectiveness of the Adolescent Coping With Depression
      (CWD-A) course, a cognitive-behavioral group intervention for depressed
      adolescents with comorbid conduct disorder. METHOD: Between 1998 and 2001, 93
      nonincarcerated adolescents (ages 13-17 years) meeting criteria for major
      depressive disorder and conduct disorder were recruited from a county juvenile
      justice department and randomly assigned to the CWD-A or a life skills/tutoring
      control condition. Participants were assessed post-treatment and at 6- and 12
      month follow-up. Dichotomous outcomes were analyzed with logistic regression;
      dimensional measures were analyzed using random effects regression. RESULTS:
      Major depressive disorder recovery rates post-treatment were greater in CWD-A
      (39%) compared with life skills/tutoring control (19%) (odds ratio 2.66, 95%
      confidence interval = 1.03-6.85). CWD-A participants reported greater reductions
      in Beck Depression Inventory-II (r2 = 0.055, p =.033) and Hamilton Depression
      Rating Scale (r2 = 0.047, p =.039) scores and improved social functioning (r2 =
      0.064, p =.019) post-treatment. Group differences in major depressive disorder
      recovery rates at 6- and 12-month follow-up were nonsignificant, as were
      differences in conduct disorder both post-treatment and during follow-up.
      CONCLUSIONS: This is the first randomized, controlled trial of a psychosocial
      intervention with adolescents with major depressive disorder and conduct
      disorder. Although the CWD-A appears to be an effective acute treatment for
      depression in adolescents with multiple disorders, findings emphasize the need to
      improve long-term outcomes for depressed adolescents with psychiatric comorbidity
      and imply that interventions for comorbid populations focus directly on each
      specific disorder.

PMID- 15167084
TI  - Treatment effects of methylphenidate on cognitive functioning in children with
      mental retardation and ADHD.
AB  - OBJECTIVE: Cognitive effects of stimulant medication were investigated in
      children with mental retardation (MR) and attention-deficit/hyperactivity
      disorder (ADHD). METHOD: Performance on tasks tapping sustained attention, visual
      and auditory selective attention, inhibition, and immediate memory was assessed
      for 24 children (mean age 10.9 years) during a placebo-controlled, double-blind,
      crossover treatment trial with 0.15, 0.30, and 0.60 mg/kg b.i.d. dosages of
      methylphenidate (MPH). RESULTS: Successively higher MPH doses were associated
      with consistent gains in cognitive task performance, with optimal performance
      noted at the highest dose. Analysis of dose-response curves revealed significant
      linear components of trend on measures tapping sustained attention, visual
      selective attention, auditory selective attention, as well as two tasks tapping
      inhibition/impulsivity: delay of gratification and match-to-sample. No evidence
      of a curvilinear dose-response relationship emerged for any measure. CONCLUSIONS:
      Inattention and disinhibition/impulsivity decline with MPH treatment in children
      with ADHD/MR, and consistent with the Multimodal Treatment Study of ADHD, higher
      MPH doses are most effective. These findings also suggest that cognitive testing,
      together with behavioral and medical assessment, can be an effective tool in
      assessing stimulant response in children with ADHD/MR.

PMID- 15167083
TI  - Pilot evaluation of the Coping Course: a cognitive-behavioral intervention to
      enhance coping skills in incarcerated youth.
AB  - OBJECTIVE: To describe the development and initial evaluation of the Coping
      Course, a cognitive-behavioral group intervention designed to enhance general
      coping and problem-solving skills among incarcerated youth. METHOD: Between 2001
      and 2002, 76 male adolescents incarcerated at a youth correctional facility were
      assessed by questionnaire and randomly assigned to either the Coping Course (n =
      46) or usual care (n = 30). Participants repeated the questionnaire after
      completion of the intervention. A second correctional facility served as an
      additional source of control group data (n = 62). RESULTS: Significant condition
      x time effects were present for seven of the examined measures: Youth Self-Report
      externalizing scores, three measures from the Life Attitudes Scale, self-esteem,
      one measure of social adjustment, and cognitive-behavioral therapy knowledge. Age
      and race/ethnicity did not moderate effects. Comparing control group participants
      with youth at a separate correctional facility who did not receive the Coping
      Course indicated that change was uniquely associated with participation in the
      intervention. CONCLUSIONS: Our goal was to take an efficacious adolescent
      depression group intervention and modify it for use with youth in correctional
      facilities. Preliminary findings are promising and provide evidence for future
      research of cognitive-behavioral group treatments with incarcerated youth.

PMID- 15167085
TI  - Effects of methylphenidate treatment in children with mental retardation and
      ADHD: individual variation in medication response.
AB  - OBJECTIVE: Individual variation in cognitive and behavioral response to
      methylphenidate (MPH) was investigated in children with mental retardation and
      attention-deficit/hyperactivity disorder. METHOD: Twenty-four children (mean age
      10.9 years, SD = 2.4) participated in a placebo-controlled, double-blind,
      crossover trial with 0.15-, 0.30-, and 0.60-mg/kg b.i.d. doses of MPH. Parent and
      teacher behavioral ratings, as well as cognitive task performance, were assessed
      at each dose. RESULTS: Relative to placebo, most children with attention
      deficit/hyperactivity disorder and mental retardation showed some degree of
      behavioral and cognitive improvement with MPH treatment. However, fewer of these
      children made substantial gains (>30% improvement, relative to placebo) with MPH
      treatment. At the highest dose, 55% of the children showed substantial behavioral
      gains and 46% made substantial gains in cognitive task performance. However,
      there was substantial independence between changes in behavior and changes in
      cognitive performance. CONCLUSIONS: At the 0.60-mg/kg MPH dose, more children
      showed substantial cognitive and behavioral gains than those who showed
      substantial declines in a ratio of more than 5:1. However, it may be prudent to
      assess cognitive change as well as behavioral effects because improvements in the
      former do not necessarily forecast improvements in the latter in children with
      attention-deficit/hyperactivity disorder and mental retardation.

PMID- 15167086
TI  - Dose-response effect of mother-infant clinical home visiting on aggressive
      behavior problems in kindergarten.
AB  - OBJECTIVE: The objective of this follow-up study was to assess the long-term
      effects of clinical infant home-visiting services on child outcomes at school
      entry. METHOD: Participants were 63 five-year-olds from low-income families, half
      of whom were referred to parent-infant home-visiting services during the first 18
      months of life due to concerns about the caretaking environment. Families
      received between 0 and 18 months of weekly home visits based on infant age at
      entry into the study. At age 5, children were rated by teachers on the Preschool
      Behavior Questionnaire for behavior problems in the classroom and by parents both
      on the Simmons Behavior Checklist for behavior problems at home and on the
      Achenbach Social Competence Items for positive play behaviors with friends.
      RESULTS: With initial family risk status and child gender controlled, teacher
      rated hostile behavior problems decreased in dose-response relation to the
      duration of early home-visiting services, which accounted for 15% of the variance
      in child hostile behavior. Parents' reports of positive play behaviors were
      positively linearly related to service duration. Parents' reports of behavior
      problems were less reliably related to service duration than teacher reports.
      CONCLUSIONS: Early home-visiting services reduced the incidence of aggressive
      behavior problems among socially at-risk children for up to 3.5 years after the
      end of services.

PMID- 15167087
TI  - ThePreschool Feelings Checklist: a brief and sensitive screening measure for
      depression in young children.
AB  - OBJECTIVE: Childhood depression is widely underrecognized in primary health care
      settings. This phenomenon appears to increase with younger age. Evidence has been
      provided for a valid depressive syndrome among preschool children. Based on the
      need for the earliest possible identification of depression, the development of a
      brief screening measure to capture young children with markers of depression from
      these community settings was developed and tested. METHOD: A group of 174
      preschool children underwent a comprehensive psychiatric assessment. The majority
      of this study group was ascertained from primary care settings using a 20-item
      checklist designed to capture depressive symptoms in young children. The
      assessment included the Diagnostic Interview Schedule for Children Version
      modified for young children and the Child Behavior Checklist. Ratings on the
      checklist were subsequently compared with these independent measures of
      psychopathology using several analytic strategies. RESULTS: The Preschool
      Feelings Checklist demonstrated high internal consistency, and 16 items showed
      strong associations with independent diagnostic measures of internalizing
      symptoms and major depressive disorder. The Preschool Feelings Checklist
      demonstrated high specificity and sensitivity for the identification of major
      depressive disorder at a cutoff score 3 or more. CONCLUSIONS: The Preschool
      Feelings Checklist is a brief and valid screening measure highly feasible for use
      in primary care settings. It demonstrated utility for the identification of
      preschoolers in need of formal mental health evaluation for depression.

PMID- 15167088
TI  - Is pubertal timing associated with psychopathology in young adulthood.
AB  - OBJECTIVE: This investigation tested whether the timing of puberty continued to
      be associated with experiences of psychopathology (symptoms and disorders) from
      mid-adolescence into young adulthood. METHOD: At age 24, 931 participants from a
      large community sample, who had been interviewed twice during adolescence,
      completed a telephone interview (assessing Axis I disorders and elevated
      antisocial and borderline personality traits) and a mailed questionnaire battery.
      RESULTS: Analyses tested whether pubertal timing was associated with lifetime and
      current history of mental disorders and psychosocial functioning in young
      adulthood. As expected, young women who had been early maturers had higher rates
      of lifetime history of disorder along with current elevation of psychosocial
      symptoms compared with women who were on-time maturers. Young men who had been
      late maturers, compared with other men, had elevated onset of disruptive behavior
      and substance use disorders during the transition to adulthood. CONCLUSIONS:
      Early maturing females are at unique risk of persistent difficulty during
      adolescence and should be targeted for preventive efforts. Late maturation among
      males may be associated with a late-onset pathway for deviant behavior or
      substance abuse.

PMID- 15167089
TI  - Prevalence of child and adolescent psychiatric disorders in southeast Brazil.
AB  - OBJECTIVE: To describe the prevalence of DSM-IV disorders and the pattern of
      comorbidity in a population-based sample of 7- to 14-year-old Brazilian
      schoolchildren. METHOD: Random sampling of schools (stratified into private,
      public rural, and public urban) was followed by random sampling of pupils from
      school lists. In 2000-2001, a total of 1,251 children were assessed for DSM-IV
      diagnoses using the Development and Well-Being Assessment, a structured
      multiinformant assessment supplemented by verbatim reports reviewed by
      clinicians. RESULTS: The response rate was 83%. The overall prevalence of DSM-IV
      disorders was 12.7% (95% confidence interval = 9.8%-15.5%), with 3.5% of children
      being assigned as not otherwise specified rather than operationalized diagnoses.
      The overall prevalence of psychiatric disorder was significantly higher than in a
      British study with the same measures and diagnostic procedures (12.7% versus
      9.7%, p =.02). CONCLUSIONS: Approximately one in eight schoolchildren in the
      study area in the southeast of Brazil have psychiatric disorders involving a
      level of distress or social impairment likely to warrant treatment. The gulf
      between need and provision is currently vast.

PMID- 15167090
TI  - ODD and ADHD symptoms in Ukrainian children: external validators and comorbidity.
AB  - OBJECTIVE: To examine potential external validators for oppositional defiant
      disorder (ODD) and attention-deficient/hyperactive disorder (ADHD) symptoms in a
      Ukrainian community-based sample of 600 children age 10 to 12 years old and
      evaluate the nature of co-occurring ODD and ADHD symptoms using mother- and
      teacher-defined groups. METHOD: In 1997, parents, children, and teachers
      participated in extensive clinical assessments using standard Western measures.
      Four areas of functioning were assessed: child mental health, parent-child
      interactions, parental well-being, and school/cognitive performance. RESULTS:
      Mother-defined ODD versus ADHD symptom groups were differentiated by a history of
      overactivity and tantrums, behavior in school, and maternal anxiety and
      hostility. Teacher-defined groups were differentiated by conduct problems,
      internalizing symptoms, mother-child interactions, and paternal alcohol use. The
      effects of co-occurring ODD and ADHD symptoms were greater than would be expected
      based on their separate effects for conduct problems, internalizing symptoms,
      social problems, academic performance, parent-child relations, and marital
      discord. CONCLUSIONS: Children with ODD versus ADHD symptoms were not
      significantly different from each other for the majority of variables examined,
      and group differences were dependent on the rater used to define symptom groups.

PMID- 15167091
TI  - Etiologies of associations between childhood sleep and behavioral problems in a
      large twin sample.
AB  - OBJECTIVE: To examine the etiologies of covariation of childhood sleep problems
      and other behavioral/emotional problems in young children. METHOD: The parents of
      more than 6,000 twin pairs provided information on their twins' anxiety, conduct,
      and hyperactivity at ages 3, 4, and 7 by completing the Strengths and
      Difficulties Questionnaire. Information on sleep problems was obtained at age
      3/4. RESULTS: Phenotypic correlations in preschool years between sleep problems
      and anxiety, conduct, and hyperactivity ranged from 0.17 to 0.22. These
      correlations were largely due to shared environmental factors (0.72-0.96) and
      less to heredity (0.05-0.26) and nonshared environment (0.00-0.06). Sleep
      problems at age 3/4 years predicted at age 7 years anxiety (beta =.12, p <.001),
      conduct problems (beta =.09, p <.001), and hyperactivity (beta =.07, p <.001),
      after accounting for stability of these problems. These predictive associations
      were also mainly mediated by shared environment (0.16-0.91), although genetic
      (0.02-0.84) and nonshared environmental (-0.03-0.09) factors were also
      influential. CONCLUSIONS: The modest associations between early sleep problems
      and later behavioral/emotional problems are largely accounted for by common
      psychosocial risk factors. Further research on which specific risks may mediate
      these connections is needed.

PMID- 15167092
TI  - Generalized anxiety disorder in referred children and adolescents.
AB  - OBJECTIVE: There are insufficient data on generalized anxiety disorder in
      children and adolescents. Symptoms and comorbidity of generalized anxiety
      disorder are described as a function of age, gender, and comorbidity in a
      consecutive series of referred children and adolescents. METHOD: One hundred
      fifty-seven outpatients (97 males and 60 females, 50 children and 107
      adolescents, age range 7-18 years, mean age 13.4 +/- 2.7 years) were diagnosed as
      having generalized anxiety disorder, using historical information and a
      structured clinical interview (Diagnostic Interview for Children and Adolescents
      Revised) according to the DSM-IV. RESULTS: Feelings of tension, apprehensive
      expectations, negative self-image, need for reassurance, irritability, and
      physical complaints were reported in more than 75% of the participants.
      Differences in symptomatology according to age and gender were nonsignificant.
      Depressive disorder was the most frequent comorbidity, being present in 56% of
      the patients. Comorbid anxiety disorders were present in about 75% of the
      patients, and 21% showed externalizing disorders. Subjects with comorbid
      depression had less anxiety comorbidity, subjects with comorbid separation
      anxiety disorder had higher rates of panic disorder, and subjects with comorbid
      externalizing disorders had higher rates of bipolar disorder. CONCLUSIONS:
      Referred children and adolescents with generalized anxiety disorder are heavily
      symptomatic and have frequent comorbidity. A more precise definition of the
      clinical picture may help early diagnosis and prevention of superimposed mental
      disorders.

PMID- 15167093
TI  - Rest-activity cycles in childhood and adolescent depression.
AB  - OBJECTIVE: To quantify circadian rhythms in rest-activity cycles in depressed
      children and adolescents. METHOD: Rest-activity cycles were evaluated by
      actigraphy over five consecutive 24-hour periods in 100 children and adolescents,
      including 59 outpatients with major depressive disorder (MDD) and 41 healthy
      normal controls. Total activity, total light exposure, and time spent in light at
      more than 1,000 lux were averaged over the recording period for each participant.
      Time series analysis was used to determine the amplitude and period length of
      circadian rhythms in rest-activity. RESULTS: Overall, adolescents with MDD had
      lower activity levels, damped circadian amplitude, and lower light exposure and
      spent less time in bright light than healthy controls. Among children, those with
      MDD showed lower light exposure and spent less time in bright light, but only
      depressed girls showed damped circadian amplitude. The sex differences were
      substantially greater in the MDD group than in the normal control group.
      CONCLUSIONS: These results confirm damped circadian rhythms in children and
      adolescents with MDD and highlight the influence of gender and age on these
      measures.

PMID- 15167095
TI  - From science to practice: The flexible use of evidence-based treatments in
      clinical settings.

PMID- 15167094
TI  - White matter hyperintensities and their associations with suicidality in
      psychiatrically hospitalized children and adolescents.
AB  - OBJECTIVE: Increasingly, researchers and clinicians are recognizing that there
      may be biological markers associated with increased risk of suicide. The
      objective of this study was to compare white matter hyperintensities in
      psychiatrically hospitalized children and youth with and without a history of
      suicide attempt while controlling for other variables. METHOD: White matter
      hyperintensities of 153 child and adolescent psychiatry inpatients were rated on
      T2-weighted magnetic resonance imaging scans using a modified Coffey scale. DSM
      IV diagnosis, history of suicide attempt, and control variables such as gender,
      age, comorbid medical illnesses, developmental disorder, substance abuse,
      severity of mental illness, head injury, and possible cerebral hypoxia were
      obtained from discharge medical records. RESULTS: Within the unipolar depression
      group (n = 48), white matter hyperintensities were significantly associated with
      a higher prevalence of past suicide attempts (Fisher exact test, p =.03).
      Logistic regression analysis confirmed this relationship, indicating that none of
      the control variables confounded our results and suggesting a specificity of
      0.94. CONCLUSIONS: This is the first report of an increased prevalence of white
      matter hyperintensities in children and youth with unipolar depression and a
      history of suicide attempt. Replication and expansion of our preliminary findings
      could be of great clinical interest.

PMID- 15167097
TI  - Computed tomography lymphography with intrapulmonary injection of iopamidol for
      sentinel lymph node localization.
AB  - PURPOSE: Experimental and clinical evaluation of the potential utility of
      indirect computed tomographic lymphography (CT-LG) with intrapulmonary injection
      of iopamidol for preoperative localization of sentinel lymph node station in non
      small cell lung cancer. METHODS: CT-LG with intrapulmonary injection of 0.5 mL of
      undiluted iopamidol was performed in 10 dogs using a multidetector-row CT unit,
      followed by postmortem examination of enhanced lymph nodes in 5 of these dogs.
      The CT-LG with peritumoral injection of 1 mL of the contrast agent was also
      performed in 9 patients with non-small cell lung cancer without lymphadenopathy.
      At surgery, enhanced lymph nodes were resected under CT-LG guide, followed by
      standard lymph node dissection with macroscopic and histologic examination. A
      significant enhancement of lymph nodes was determined when CT attenuation value
      was increased with 30 Hounsfield units (HU) compared with precontrast images.
      RESULTS: CT-LG visualized a total of 15 enhanced lymph nodes (on average, 1.5
      nodes per animal) within 2 minutes after contrast injection in the 10 dogs, with
      average size of 6.7+/- 1.9 mm and average maximum CT attenuation of 149 +/- 41
      HU. All the 8 enhanced nodes in 5 dogs were found in the appropriate anatomic
      locations in postmortem examinations. Without noticeable complications, CT-LG
      visualized 30 ipsilateral intrathoracic lymph nodes including 19 hilar/pulmonary
      and 11 mediastinal nodes in the 9 patients (on average, 2.2 hilar/pulmonary and
      1.1 mediastinal nodes per patient) within 2 minutes after contrast injection,
      with average size of 4.7+/- 0.4 mm and average maximum CT attenuation of 134 +/-
      52 HU. At surgery, all these enhanced nodes could be accurately found and
      resected under CT-LG guidance. Metastasis was not evident in either of these
      enhanced lymph nodes or the remaining distant nodes in all patients. CONCLUSION:
      Quick and accurate localization of sentinel lymph node station on detailed
      underlying lung anatomy by using indirect CT-LG may be of value to guide
      selective lymph node dissection for minimally invasive surgery in non-small cell
      lung cancer.

PMID- 15167098
TI  - Comparison of an automatic versus a semiautomatic mode for gray-scale adaptation
      for digital chest radiography.
AB  - PURPOSE: To compare image quality of digital chest radiographs using 2 modes of
      gradation adjustment. METHODS: We compared image quality and visualization of
      anatomic landmarks of 50 chest radiographs after digital processing using a
      semiautomatic mode with a fixed gamma of 2.6 and an automatic mode with
      individual gamma adaptation. RESULTS: The mean gamma was significantly higher (P
      < 0.001) with the automatic mode (3.0 vs. 2.6, respectively). Patient
      constitution had no impact on the automatically adapted gamma for PA but showed a
      significant correlation (P < 0.001) for lateral images. For PA, there was a
      preference (P < 0.016) of the semiautomatic mode in heavier patients whereas no
      difference was seen in slim patients. For the lateral projection, there was a
      general preference (P = 0.001) of the automatic mode. CONCLUSION: For PA
      radiographs, the semiautomatic mode provides superior results for heavier
      patients without compromising the quality in slim patients. For lateral
      radiographs, the automatic mode provides generally superior results.

PMID- 15167099
TI  - Pharmacokinetics and safety of the MRI contrast agent gadoversetamide injection
      (OptiMARK) in healthy pediatric subjects.
AB  - RATIONALE AND OBJECTIVE: This clinical trial examined the pharmacokinetics of
      gadoversetamide, a magnetic resonance imaging contrast agent, in normal pediatric
      subjects. MATERIALS AND METHODS: Seventeen healthy pediatric subjects received a
      single intravenous injection of gadoversetamide (0.1 mmol/kg, 0.2 mL/kg). Sixteen
      subjects that were evaluable for pharmacokinetic analysis fell into 2 stratified
      age groups: 2 years to <5 years and 5 years to <18 years of age. Serum samples
      were analyzed for total gadolinium as a measure of gadoversetamide concentration.
      RESULTS: Statistical analysis demonstrated significant (P < 0.05) age-related
      trends in the mean elimination half-life (t 1/2) of gadolinium with the older
      group having a slightly longer t 1/2 (1.39 hours) than the younger group (1.19
      hours). No age-related changes occurred in volume of distribution or total body
      clearance, when normalized to body weight or body surface area. CONCLUSIONS:
      Based on this preliminary pharmacokinetic assessment, no adjustment from the
      approved adult gadoversetamide dose of 0.1 mmol/kg should be necessary for
      children aged 2 or older.

PMID- 15167100
TI  - Quantitative evaluation of perfusion and permeability of peripheral tumors using
      contrast-enhanced computed tomography.
AB  - RATIONALE AND OBJECTIVES: Our purpose was to validate contrast-enhanced computed
      tomography (CECT)-derived quantitative measures of perfusion and permeability
      against gold standard techniques of fluorescent microspheres and Evan's Blue dye,
      respectively. MATERIALS AND METHODS: Normal and tumor-bearing (R3230AC) Fischer
      344 rats were used. CECT perfusion measurements of normal and tumor tissue were
      compared with quantitative fluorescent microsphere perfusion measures. CECT
      permeability measurements from tumors were compared with semiquantitative Evan's
      Blue Dye permeability estimates. CT images were obtained precontrast and an
      imaging plane was selected. Serial, stationary images were obtained every 2
      seconds for 2 minutes after intravenous bolus of iodinated contrast. Permeability
      and perfusion were measured by applying Patlak analysis to time-density data from
      normal tissue or tumor and femoral artery. RESULTS: There was good correlation
      between fluorescent microsphere and CECT measurements of perfusion (r2 = 0.681, P
      << 0.001) and between Evan's Blue Dye and CECT measurements of permeability (r2 =
      0.873, P = 0.0007). CONCLUSIONS: CECT provides useful, quantifiable measures of
      perfusion and permeability in peripheral tumors.

PMID- 15167101
TI  - Validation of a new method for quantifying in vivo murine tumor necrosis by
      sonography.
AB  - RATIONALE AND OBJECTIVES: At present, the gold standard to evaluate tumor
      necrosis is histology. We described here a new method to quantify the degree of
      tumor necrosis by ultrasonography. This technique combines ultrasound exploration
      of tissue and post-treatment of the numerical sequences using a dedicated
      software to evaluate backscattered power within the tumor. MATERIALS AND METHODS:
      In order to establish that the backscattered power could be considered as a
      relevant marker of tumor necrosis, we performed (1) intra- and interoperator
      reproducibility in estimation of tumor dimensions obtained on sonographic scans;
      and (2) intra- and interoperator reproducibility in quantification of
      backscattered power in postprocessing using the HDILab software. The third part
      of the study consisted of correlating the degree of tumor necrosis estimated by
      histology and the ultrasound backscattered power, both obtained on xenografted
      melanomas at different days after tumor transplantation. RESULTS: Results
      concerning tumor size estimations and quantification of echogenicity were
      reproducible (coefficient of variation < 4.33%). The degree of necrosis measured
      in histology and echogenicity were significantly negatively correlated (P <
      0.003). CONCLUSION: In conclusion, backscattered power could be considered as a
      relevant parameter to quantify tumor necrosis in vivo.

PMID- 15167102
TI  - Image quality of noninvasive coronary angiography using multislice spiral
      computed tomography and electron-beam computed tomography: intraindividual
      comparison in an animal model.
AB  - OBJECTIVE: Comparison of coronary artery visualization by multislice spiral CT
      (MSCT) and electron-beam CT (EBCT). MATERIALS AND METHODS: Six minipigs underwent
      MSCT (collimation 4 x 1 mm, gantry rotation time 500 milliseconds, acquisition
      time per cardiac cycle 126 +/- 30 milliseconds) and EBCT (slice thickness 1.5 mm,
      acquisition time per scan 100 milliseconds). Visualized vessel length and contour
      sharpness was measured, contrast-to-noise ratios were calculated, and the
      frequency of motion artifacts were evaluated. RESULTS: MSCT depicted
      significantly longer segments of the coronary tree than EBCT (length: 248.8 vs.
      222.8 mm; P < 0.05), delineated the vessel contours more sharply (slope of
      density curves: 219.2 vs. 160.2 DeltaHU/mm; P < 0.05), and had a higher contrast
      to-noise ratio (13.4 vs. 7.3; P < 0.05). The frequency of motion artifacts did
      not differ between both modalities (94.7% vs. 95.7% of visualized vessel length;
      P > 0.05). CONCLUSIONS: Because its higher spatial resolution and lower image
      noise, MSCT seems to be superior to EBCT in the visualization of the coronary
      arteries. Despite different temporal resolutions motion artifacts seem to be
      similar with both modalities.

PMID- 15167103
TI  - Quantitative assessment of the morphology of renal arteries from X-ray images:
      quantitative vascular analysis.
AB  - RATIONALE AND OBJECTIVES: With the advent of interventional vascular procedures,
      objective and reproducible tools are needed to assist clinical decision-making
      and to assess intervention efficacy. The success of quantitative coronary
      arteriography (QVA) in objectively assessing cardiovascular morphology has
      initiated the software development for quantitative analysis of peripheral
      vasculature. The objective of this study was to evaluate the applicability and
      quality of a new QVA package applied to renal arteries. METHODS: A calibration
      method was developed using markers mounted on a catheter's shaft, ensuring
      accurate calibration even with small catheter sizes. Given the high prevalence of
      ostial stenoses in peripheral vessels, a dedicated vessel analysis method was
      developed to assess these stenoses. Its reproducibility was determined in renal
      angiography. Variance component analysis was performed to evaluate sources of
      variability, using angiograms from 74 patients suspected of renovascular
      hypertension. RESULTS: For intraobserver variability, the 95% confidence
      intervals of differences in percent diameter stenosis and minimal lumen diameter
      were -1.99%-1.04% (P = 0.53, n = 48) and -0.081 mm-0.023 mm (P = 0.27, n = 48),
      respectively. For the interobserver variability, intervals were -1.86%-2.80% (P =
      0.69, n = 66) and -0.46 mm-0.053 mm (P = 0.12, n = 46), respectively.
      CONCLUSIONS: The contribution of intraobserver variation was negligible. The
      contribution of interobserver variation for different parameters was negligible
      or comparable with the variation caused by image acquisition. These conclusions
      demonstrate that QVA can reproducibly measure renal artery geometry.

PMID- 15167104
TI  - Experimental functional analysis of self-expanding stents using a new developed
      ex vivo model.
AB  - OBJECTIVE: To modify an ex vivo test procedure for balloon expandable stents as a
      means to evaluate the mechanical properties of self-expanding stents. METHODS:
      Ten stents each of 7 different stent models measuring 10 mm in diameter (LUMINEXX
      Vascular Stent/Memotherm-FLEXX Vascular Stent [identical to Bard], Jostent SelfX,
      Jostent SelfX high radial force [Jomed], sinus-Repo stent, sinus-SuperFlex stent
      [Optimed], S.M.A.R.T. stent [Cordis], and Easy Wallstent [Boston Scientific])
      were implanted in common iliac arteries taken from cadavers (n = 35). They were
      randomized to either the right or left bifurcation. The vessels were then
      maintained at 37 degrees C for 24 hours in a special solution that inhibited
      autolysis, making it possible for the stents to expand. Afterward, they were
      filled with silicone caoutchouc. After another 24 hours, the vessel walls and
      stents were removed from the hardened casts. By means of fine analytic
      measurements, we demonstrated that the volume of a hardened cast formed in the
      stent cylinder is an indirect but precise measure of the radial force of a stent.
      Furthermore, using correlation analysis, we examined the relationship between
      radial force and vessel diameter as well as that between radial force and the
      degree of arteriosclerosis. RESULTS: The differences between the actually
      measured volumes, ie, radial strength, (1 cm stent length) of the various stent
      models (LUMINEXX/Memotherm-FLEXX: 0.6198 mL +/- 0.1537 mL; Jostent SelfX: 0.6756
      mL+/- 0.1298 mL; Jostent SelfX high radial force: 0.6321 mL+/- 0.1817 mL; sinus
      Repo stent: 0.5508 mL+/- 0.1485 mL; sinus-SuperFlex stent: 0.6174 mL+/- 0.0953
      mL; S.M.A.R.T. stent: 0.5627 mL+/- 0.1270 mL; and Easy Wallstent: 0.5613 mL+/-
      0.1019 mL) were not statistically significant (P > 0.05), but the differences to
      the theoretically possible volumes that we had previously calculated were highly
      significant (P < 0.05). Correlation and regression analyses demonstrated a
      significantly stronger relationship between stent volume and vessel diameter than
      between stent volume and degree of arteriosclerosis. CONCLUSION: The modification
      of our ex vivo model of balloon-expandable stents now makes it possible for
      researchers to obtain comparable and realistic values for both the radial force
      and the expansion of self-expanding stents under realistic conditions. Our
      methods should therefore be employed as an additional procedure to optimize the
      preclinical evaluation of new stent during certification.

PMID- 15167105
TI  - Rehabilitation in Germany: new challenges of a structured social security scheme.
AB  - The structured social security scheme established in Germany is clearly reflected
      in the configuration of the German rehabilitation system. For medical
      rehabilitation the institutions of statutory pension insurance and statutory
      health insurance are of particular importance. Within the past decades
      differentiated supply structures were built up and re-built within the
      rehabilitation system. As a consequence, insured parties receive different
      rehabilitation benefits depending on which insurance is responsible. This article
      outlines central elements of the German rehabilitation supply structure as well
      as the numerous rehabilitation forms and benefits. Moreover, perspectives of a
      recently passed law of rehabilitation and the participation of handicapped people
      (SGB IX) (SGB=social law), which forces insurers into increased co-operation and
      restructuring, are presented.

PMID- 15167106
TI  - Vocational rehabilitation: what works and in what circumstances.
AB  - This paper examines a variety of forms of evidence used to find the effectiveness
      of vocational rehabilitation interventions. We begin by looking at general
      unemployment literature and then study the detailed findings of a research
      project that examined the employment experiences of disabled people, carried out
      by one of the authors. We then report on a recent evaluation of an innovative
      vocational rehabilitation scheme. Here, following the approach recommended by
      Pawson and Tilley (1997), we consider the views of one of the project
      'stakeholders' concerning the 'theories' underlying the design of the project. In
      conclusion we encapsulate some of the knowledge, or evidence, emerging from these
      diverse sources in configurations of contexts, mechanisms and outcomes, as
      advocated by Pawson and Tilley.

PMID- 15167107
TI  - Caregiving problems and feelings experienced by family caregivers of stroke
      survivors the first month after discharge.
AB  - The purpose of this study was to identify the major problems and associated
      feelings experienced by family caregivers of stroke survivors during the first
      month after returning home. Safety, difficulty in managing activities of daily
      living, and cognitive, behavioral and emotional changes of stroke survivors (for
      example, mood swings, lack of motivation, forgetfulness and memory loss,
      depression and calling the caregiver often) were the three most common problems
      experienced by caregivers during the first month. Other problems were loss of
      caregiver independence, confinement, tiredness and inadequate time to do
      caregiving tasks as well as managing stroke survivor physical symptoms, for
      example, pain, not eating and skin problems. The first month of caregiving is
      very dynamic and distressful for caregivers of stroke survivors and telephone
      contacts appear to be beneficial in assisting caregivers to cope with the
      caregiving process.

PMID- 15167108
TI  - Is information and communication technology an opportunity for parents of
      children with disabilities?
AB  - The main themes of this article are parents' expectations, experiences and
      influence of information and communication technology and children with
      disabilities. This article will focus on how parents of children with
      disabilities experience 7 months of computer activities together with their
      children. The results indicated that expectations comprise several aspects. The
      central theme is the parents' sincere hope that their children will be able to
      participate actively in society and have the same opportunities as other
      children.

PMID- 15167109
TI  - Effectiveness of home rehabilitation after stroke in Israel.
AB  - On discharge from an acute general hospital after a stroke, 191 patients were in
      need of, and were appropriate for, multidisciplinary rehabilitation. One-hundred
      and-one patients (52.4%) received it in a rehabilitation institution as
      inpatients (the institutional rehabilitation group (IR) group) and 91 patients
      received it at home (the home rehabilitation (HR) group). Patients in the HR
      group had their mobility, activities of daily living (ADL), range of movements,
      tonus, coordination and sensation determined on admission to home rehabilitation
      and on discharge from it, 6 weeks to 2 months later. This group contained more
      women and more patients able to walk with devices and who were partially
      independent in ADL. The IR group consisted of more men and more patients with
      diabetes and marked difficulties in ADL and ambulation. In both groups the
      Barthel index and the Frenchay activities index were determined 1 year after the
      stroke by way of a telephone interview and no meaningful differences were found
      between the two groups. IR was considerably more expensive than HR. In Israel
      there exists a subpopulation of acute stroke survivors in need of, and
      appropriate for, multidisciplinary rehabilitation that can be provided at home;
      such rehabilitation was found to be effective in the short and long term, as well
      as cost effective.

PMID- 15167110
TI  - Organizational aspects of special schools for mental retardation in India.
AB  - The aim of this study was to find out areas for improvement in the system of
      special schools for mental retardation in India and to provide policy guidance.
      It attempted to find out regional variations between special schools in terms of
      service facilities, numbers of students enrolled in both day-care and residential
      facilities and composition and profile of human resources vis-a-vis students and
      special schools and to compare them with trends for the whole of India. The
      results indicate that enrollment of girl students is very low (37%) and that the
      staff-to-student ratio on average is 1:6 leaving scope for better utilization of
      the existing infrastructure. The study points out that the south and west regions
      account for 73% of special educational facilities while 26% of the schools
      provide residential facilities. Further the results indicate that only 31% of the
      special schools provide early intervention and early childhood education
      facilities. They also indicate that composition and deployment of staff is
      lopsided and there are wide variations among regions and within the different
      categories of staff. It is observed that staff profile comprises 51% special
      teachers, 31% rehabilitation professionals and 18% support staff. Based on the
      findings, seven major areas have emerged for improvement: regional balance in the
      growth of special schools, comprehensive services, equality between the sexes,
      full-time, qualified staff and optimal utilization of the existing
      infrastructure.

PMID- 15167111
TI  - Length of stay in the rehabilitation center, the admission functional
      independence measure and the functional independence measure gain.
AB  - The decision to discharge is an important factor determining the length of stay
      (LOS) in a rehabilitation center and should be scrutinized. The purpose of this
      study was to analyse the predictive power of the individual items of the
      admission functional independence measure (FIM) for the LOS indicating their
      relevance in the decision to discharge and to expose the assumptions driving this
      decision. The data of all consecutive in-patients of 5 years in a rehabilitation
      center were analysed (n=1047). The regression analysis of FIM item values on
      admission and FIM item gains as independent variables and the LOS as the
      dependent variable showed a number of criteria operational in the decision to
      discharge patients with different diagnoses. The criteria were identified as
      'aiming for certain standards' (for example, bed/chair/WC transfer), 'aiming for
      optimal improvement', 'dealing with different rates of improvement' and 'giving
      benefit of learning potential'. It is proposed that these criteria should be
      discussed and evaluated.

PMID- 15167112
TI  - Is performance on the Wechsler Abbreviated Scale of Intelligence associated with
      employment outcome following brain injury?
AB  - Return to work represents a significant marker of functional outcome for persons
      who have suffered a brain injury. Neuropsychological assessment forms an integral
      part of treatment planning following brain injury and aims to document cognitive
      strengths and weaknesses, including general intellectual abilities.
      Neuropsychological testing has been criticised for having limited ability to
      predict functional outcomes such as return to work. The present study sought to
      examine the association between return to work following ABI and the Wechsler
      Abbreviated Scale of Intelligence (WASI). Patient files in a community
      neurorehabilatation service were reviewed retrospectively and 52 individuals were
      identified who had been employed at the time of their injury and for whom a WASI
      was completed. The study found full-scale IQ, verbal IQ, the similarities sub
      test, and severity of injury to be associated with return to work.

PMID- 15167114
TI  - Measurement properties of the short form (SF)-12 applied to patients with stroke.
AB  - The purpose of this study was to examine the reliability and validity of the
      Short Form (SF)-12 and to determine its ability to detect changes in health
      related quality of life (HRQOL) following stroke. The study involved a cohort of
      90 patients admitted with an ischemic stroke to a hospital in the northeastern
      United States. The items of the SF-12 were found to be reliable (alpha=0.833
      0.894) and to load on a physical and mental component. Three months post-stroke
      the physical component summary (PCS) scores of the SF-12 were significantly less
      than population norms. The PCS scores were also lower after stroke (3 month=42.5,
      12 month=46.3) than before stroke (48.8). Mental component summary (MCS) scores
      did not differ significantly from population norms or across time (range=53.6 to
      54.9). We conclude that the reliability and validity of the SF-12, as well as its
      brevity and capacity to document changes in the physical component of HRQOL,
      provide support for its use in patients with stroke.

PMID- 15167113
TI  - Test-retest reliability of short form (SF)-12 component scores of patients with
      stroke.
AB  - Although the Short Form (SF)-12 has been used previously to characterize the
      health related quality of life of patients with stroke, its test-retest
      reliability has not been described for such patients. We, therefore, examined
      this reliability in 31 patients (mean age=66.5 years) who experienced an ischemic
      stroke 3-12 months previously. Patients were contacted twice (mean interval=16.2
      days) by telephone. Physical component and mental component scores were derived
      from the 12 SF items. Scores differed less than 1.5 points between tests and were
      not significantly different. Intraclass correlation coefficients surpassed 0.800.
      The findings support the test-retest reliability of physical and mental component
      scores of the SF-12 administered by telephone to post-stroke patients.

PMID- 15167115
TI  - Allocation and preference of patients for domiciliary or institutional
      rehabilitation after a stroke.
AB  - On discharge from an acute-care hospital after a stroke, 191 patients were told
      that they needed rehabilitation and were offered the option of receiving care in
      an institution or in their homes. One hundred and one (52.4%) patients chose an
      institution and 91 (47.6%) preferred rehabilitation in their own home. A higher
      number of women than men chose to be rehabilitated at home. Multivariate logistic
      regression showed that odds for being included in the home rehabilitation group
      were higher for women and for those who had a stroke in the past. Odds for being
      included in the institutional rehabilitation group were individuals with diabetes
      and difficulty in ambulating and those who had a longer stay in the acute-care
      hospital. Findings of the study suggest that in Israel there is a sub-population
      of acute stroke survivors who may be appropriate for rehabilitation at home and
      accept the option when they are offered it.

PMID- 15167116
TI  - Validation of the Chinese general self-efficacy scale among individuals with
      schizophrenia in Hong Kong.
AB  - The concept of self-efficacy has recently produced considerable interest among
      mental illness researchers. Self-efficacy was found to be associated with the
      number of hospitalizations, social adjustment, rehabilitation outcome, and levels
      of positive symptoms among individuals with schizophrenia. Given its escalating
      importance in psychiatric rehabilitation, a scale to assess self-efficacy with
      established psychometric properties is urgently needed. Validated scales that
      measure self-efficacy of Chinese with severe mental illness are however extremely
      limited. The Chinese General Self-efficacy Scale (CGSS) was generic in design and
      had not been validated for use with people with mental illness. The purpose of
      this study is to examine psychometric properties of CGSS for use among persons
      with schizophrenia in Chinese societies. The content validity of items was
      endorsed by a panel of 8 rehabilitation professionals with 75% to 100% of
      agreement. The scale was tested in sample of 78 individuals with schizophrenia
      and found to have excellent internal consistency (0.92-0.93) and very good to
      excellent test re-test reliability (0.75-0.94). Exploratory factor analysis
      yielded a two-factor solution explaining 69.0% of variance which was different
      from overseas studies which showed the scale to be unidimensional. The scale was
      concluded to be reliable and valid to assess self-efficacy of Chinese with
      schizophrenia. Potential uses of this scale were suggested.

PMID- 15167117
TI  - An assessment of osteoporosis in stroke patients on rehabilitation admission.
AB  - This paper looks at the proportion of patients who were already at risk of
      osteoporosis by measuring bone mineral density (BMD) and bone resorption, and to
      examine the relationships between BMD, age, gender and the levels of disability.
      83 stroke patients were admitted to a rehabilitation ward in the National
      Nagasaki Hospital (Japan), between September 2000 and November 2001. The mean
      time from onset was 38.9 days. Of these, approximately 40% of patients had
      osteoporosis with a T-score of hip BMD of -2.5 SD or more below. Correlations
      were found between BMD (T-score), age and gender but not sides. Increased bone
      resorption was significant in female patients and it was also associated with
      age, the Brunnstrom motor recovery scores and the Barthel Index scores but not
      BMD at hips. This study suggests the need for attention to osteoporosis in sub
      acute stroke patients. In addition to ordinary stroke rehabilitation, extra
      approaches/interventions will be necessary for such patients in order to prevent
      post stroke fracture.

PMID- 15167118
TI  - Self-reported efficacy of an ear-level prosthetic device that delivers altered
      auditory feedback for the management of stuttering.
AB  - Numerous past efficacy studies in stuttering treatment have typically failed to
      assess generalization of therapeutic gains across speaking environments over
      time. The purpose of this study was to use a self-report format to gain insight
      into the improvements of clients who purchased an all in-the-ear device that
      provides altered auditory feedback to manage stuttering symptoms across everyday
      speaking situations. A total of 105 participants (age 7-81 years) returned
      completed questionnaires that examined seven parameters of stuttering behavior
      before acquiring the prosthetic device and after using the device with minimal
      clinical intervention for an average of 6 months. Across each parameter,
      participants rated a significant (P<0.001) improvement of approximately two units
      on seven-point scales after beginning to use the prosthetic device. In addition,
      the device received high overall satisfaction ratings, with a median score of 2.0
      on the seven-point scale. Self-report is a 'must' for examining clinical efficacy
      in a disorder such as stuttering, which is so amenable to 'clinic room fluency'
      yet highly resistant to long-term amelioration. The data suggest that this device
      is helping to provide its users with functional, effective and efficient
      management of stuttering without the need for extended clinical follow-up.

PMID- 15167120
TI  - Individual thyroid dose estimation for a case-control study of Chernobyl-related
      thyroid cancer among children of Belarus-part I: 131I, short-lived radioiodines
      (132I, 133I, 135I), and short-lived radiotelluriums (131MTe and 132Te).
AB  - Large amounts of radioiodines were released into the atmosphere during the
      accident at the Chernobyl nuclear power plant on 26 April 1986. In order to
      investigate whether the thyroid cancers observed among children in Belarus could
      have been caused by radiation exposures from the Chernobyl accident, a team of
      Belarusian, Russian, and American scientists conducted a case-control study to
      compare cases and controls according to estimated thyroid dose. The primary
      purpose of this paper is to present detailed information on the estimated thyroid
      doses, due to intakes of 131I, that were used in the case-control study. The
      range of the 131I thyroid doses among the 107 cases and the 214 controls was
      found to extend from 0.00002 to 4.3 Gy, with medians of approximately 0.2 Gy for
      the cases and 0.07 Gy for the controls. In addition, the thyroid doses resulting
      from the intakes of short-lived radioiodines (132I, 133I, and 135I) and
      radiotelluriums (131mTe and 132Te) were estimated and compared to the doses from
      131I. The ratios of the estimated thyroid doses from the short-lived
      radionuclides and from I for the cases and the controls range from 0.003 to 0.1,
      with median values of approximately 0.02 for both cases and controls.

PMID- 15167119
TI  - Dietary intakes of seven elements of importance in radiological protection by
      asian population: comparison with ICRP data.
AB  - Within the framework of a Coordinated Research Project (CRP) organized by the
      International Atomic Energy Agency, Vienna, the daily dietary intakes of seven
      elements by adult populations living in nine Asian countries were estimated. The
      countries that participated in the study were Bangladesh, China, India,
      Indonesia, Japan, Pakistan, Philippines, South Korea (Republic of Korea, ROK),
      and Vietnam and together they represented more than half of the world population.
      The seven elements studied were calcium, cesium, iodine, potassium, strontium,
      thorium, and uranium. These elements have chemical and biological similarity to
      some of the radionuclides abundantly encountered during nuclear power production
      and therefore data on these elements could provide important information on their
      biokinetic behavior. Analyses of diet samples for these seven elements were
      carried out using highly sensitive and reliable analytical techniques. One
      thousand one hundred and sixty analytical determinations were made on two hundred
      and twenty samples of typical diets consumed in these countries to estimate the
      daily intakes of these elements by the adult Asian population. The median daily
      dietary intakes for the adult Asian population were found to be 0.45 g calcium, 7
      microg cesium, 90 microg iodine, 1.75 g potassium, 1.65 mg strontium, 1 microg
      thorium, and 1 microg uranium. When compared with the intakes proposed for ICRP
      Reference Man by International Commission for Radiological Protection, these
      intakes were lower by factors of 0.41 for calcium, 0.7 for cesium, 0.45 for
      iodine, 0.53 for potassium, 0.87 for strontium, 0.33 for thorium, and 0.52 for
      uranium. The lower daily intakes of calcium, cesium, and iodine by Asian
      population could be due to significantly lower consumption of milk and milk
      products, which are rich in these elements. The significantly lower intake of
      calcium in most of the Asian countries may lead to higher uptake of fission
      nuclide 90Sr and could result in perhaps higher internal radiation dose. The use
      of highly sensitive and reliable analytical methods resulted in accurate and
      lower intake values obtained for thorium and uranium, which suggest that
      radiation dose from their ingestion at natural background levels is likely to be
      lower than what may be concluded from ICRP data.

PMID- 15167121
TI  - Limitations on upper bound dose to adults due to intake of 129I in drinking water
      and a total diet-implications relative to the proposed Yucca Mountain high level
      radioactive waste repository.
AB  - The purpose of this report is to comment on the potential annual doses due to the
      intake by adults of I, an important radionuclide in the proposed high-level
      radioactive waste repository at Yucca Mountain. An often overlooked, but
      significant, factor is that, in this case, the ground water, which would be the
      primary transport vehicle for any releases, contains relatively high
      concentrations of stable iodine (127I); in fact, the median concentration in the
      ground water in the vicinity of the proposed repository is 5.0 microg L-1. In
      comparison, the maximum concentration of 129I in the ground water, due to
      potential releases of 129I during the first 10,000 y following closure of the
      repository, is estimated to be approximately 3.7 x 10(-7) Bq L-1 (approximately
      10(-5) pCi L-1). This would result in a 127I to 129I ratio in the water of almost
      90 million to one. Assuming no other sources of these two isotopes were being
      consumed, this would place an upper bound on the annual committed thyroid dose of
      1.2 x 10(-1) mSv (1.2 x 10(-1) mrem), less than one thousandth of the Ground
      Water Protection Standard of 4 mrem y-1. When the additional intake of stable and
      radioactive iodine in other components of the diet is considered, the overall
      ratio of 127I to 129I would be more than 2 billion to one. The would place an
      upper bound on the annual committed effective dose of approximately 2.5 x 10(-8)
      mSv (approximately 2.5 x 10(-6) mrem), less than one millionth of the Individual
      Protection Standard of 0.15 mSv (15 mrem).

PMID- 15167122
TI  - Survival and bone tumor hazard from internal deposition of 226Ra in beagles.
AB  - The survival of 132 young adult control beagles and 117 beagles receiving graded
      injections of 226Ra ranging from 0.27 kBq kg-1 to 384.2 kBq kg-1 body mass was
      analyzed. The hazards of natural deaths, all deaths in injection groups, and
      deaths by bone tumors were assumed to follow a Weibull distribution with a common
      shape factor of 6.3. Only the scale factors of the Weibull distributions depend
      on the injection level. There were no significant sex differences. The relative
      risk with respect to controls for all causes of death increases up to 6,925 for
      384.2 kBq kg-1. The dependence of the scale factors for all deaths and death by
      bone tumors on injected activity was fitted to an empirical regression model,
      which also contains a term representing radiation-caused deaths other than bone
      tumors. The risk of bone tumors increases nearly as the square of the injected
      activity, whereas the risk of the other radiation caused deaths increases
      approximately in proportion to the injected activity. By means of the regression
      model, it is possible to predict median survival times for all deaths, bone tumor
      and non-bone tumor deaths for an arbitrary intake level. Also, simple expressions
      for the fraction of animals with bone tumors and other radiation-caused deaths
      can be derived. The empirical model of bone tumor induction, which was based on
      results from a single injection design, can be generalized to an arbitrary
      systemic intake schema. This is achieved by using the average dose and dose rate
      to the skeleton as indices of detriment. Applying the generalized model, it was
      confirmed that no significant differences in survival can be expected for two
      groups of beagles receiving multiple injections, if compared to the corresponding
      single injection groups of about the same total activity. The general model also
      predicts that even extensive protraction of the intake would increase the
      survival times only to a very limited extent.

PMID- 15167123
TI  - PRESCILA: a new, lightweight neutron rem meter.
AB  - Conventional neutron rem meters currently in use are based on 1960's technology
      that relies on a large neutron moderator assembly surrounding a thermal detector
      to achieve a rem-like response function over a limited energy range. Such rem
      meters present an ergonomic challenge, being heavy and bulky, and have caused
      injuries during radiation protection surveys. Another defect of traditional rem
      meters is a poor high-energy response above 10 MeV, which makes them unsuitable
      for applications at high-energy accelerator facilities. Proton Recoil
      Scintillator-Los Alamos (PRESCILA) was developed as a low-weight (2 kg)
      alternative capable of extended energy response, high sensitivity, and moderate
      gamma rejection. An array of ZnS(Ag) based scintillators is located inside and
      around a Lucite light guide, which couples the scintillation light to a sideview
      bialkali photomultiplier tube. The use of both fast and thermal scintillators
      allows the energy response function to be optimized for a wide range of
      operational spectra. The light guide and the borated polyethylene frame provide
      moderation for the thermal scintillator element. The scintillators represent
      greatly improved versions of the Hornyak and Stedman designs from the 1950's, and
      were developed in collaboration with Eljen Technology. The inherent pulse height
      advantage of proton recoils over electron tracks in the phosphor grains
      eliminates the need for pulse shape discrimination and makes it possible to use
      the PRESCILA probe with standard pulse height discrimination provided by off-the
      shelf health physics counters. PRESCILA prototype probes have been extensively
      tested at both Los Alamos and the German Bureau of Standards, Physikalisch
      Technische Bundesanstalt. Test results are presented for energy response,
      directional dependence, linearity, sensitivity, and gamma rejection. Initial
      field tests have been conducted at Los Alamos and these results are also given.
      It is concluded that PRESCILA offers a viable, ergonomically superior,
      alternative to traditional rem meters that is effective for a wide range of
      neutron fields. The probe is capable of excellent sensitivity (40 counts per
      minute per microSv h-1 for 241AmBe) and extended energy response to beyond 20
      MeV. Directional response is uniform (+/-15%) over a wide range of energies.
      Response linearity has been characterized to over 20 mSv h-1. Gamma rejection is
      effective in gamma fields up to 2 mSv h-1. The PRESCILA technology has been
      commercialized and is now offered under license by Ludlum Measurements, Inc.

PMID- 15167124
TI  - A leak quantification method using sulfur hexafluoride as tracer gas.
AB  - Filter holders and continuous air monitors are used extensively in the nuclear
      industry. It is important to minimize leakage in these devices, and, in
      recognition of this consideration, a limit on leakage for sampling systems is
      specified in; however, the protocol given in the standard is really germane to
      measurement of significant leakage, e.g., several percent of the sampling flow
      rate. In the present study, we developed a technique for quantifying leakage and
      used that approach to measure the sealing integrity of a continuous air monitor
      and two kinds of filter holders. The methodology involves use of sulfur
      hexafluoride as a tracer gas with the device being tested operated under dynamic
      flow conditions. The leak rates in these devices were determined in the pressure
      range from 2.49 kPa (10 inches H2O) vacuum to 2.49 kPa (10 inches H2O) pressure
      at a flow rate of 56.6 L min-1 (2 cfm). For the two filter holders, the leak
      rates were less than 0.007% of the nominal flow rate. The leak rate in the
      continuous air monitors was less than 0.2% of the nominal flow rate. These values
      are well within the limit prescribed in the ANSI standard, which is 5% of the
      nominal flow rate. We suggest that the limit listed in the ANSI standard should
      be reconsidered as lower values can be achieved, and the methodology presented
      herein can be used to quantify lower leakage values in sample collectors and
      analyzers.

PMID- 15167125
TI  - Radon activity levels and effective doses in the Perama Cave, Greece.
AB  - An investigation of atmospheric radon levels in the Perama Cave, North-western
      Greece, has been carried out using CR-39 detectors. The detectors were placed at
      various locations along the guided cave pathway and exposed during different
      sampling periods. Mean concentrations amounting to 925 +/- 418 and 1,311 +/- 352
      Bq m-3 were recorded in the summer and winter months, respectively. As the Perama
      Cave is one of the most popular in Greece, attracting more than 85,000 tourists
      per year, the quantification of effective doses to staff and visitors was an
      issue of importance. Doses less than 5.1 microSv per visit were calculated for
      tourists and around 1.8 mSv y-1 for seasonal guides, employed for periods of high
      visiting frequency. The annual exposure of permanent guides was estimated to fall
      between 3 and 10 mSv, which is the range of action levels recommended by the
      ICRP.

PMID- 15167126
TI  - Does malignant hematopoietic disease result from internal exposure to 239Pu?
AB  - Neither Fisher's Exact Test nor linear regression analysis (dose-response
      relationship) using average skeletal dose from 239Pu as a surrogate for marrow
      dose could establish a statistically significant association between malignant
      hematopoietic disease (MHD including leukemia and aleukemia) and exposure to
      239Pu among dogs in the Utah beagle colony. In addition, when dog-years at risk
      was the parameter used to estimate the rate of expected malignant hematopoietic
      tumors in dogs exposed to 239Pu, the estimate was within the range of the 95%
      confidence limits of the control dogs for six cases (and also within the 95%
      confidence limits for five cases when the single case of lymphoma was omitted).
      It was concluded that if there was an effect of 239Pu exposure on the occurrence
      of MHD in this beagle experiment, it was not very meaningful. These data could
      not establish a significant susceptibility to neoplasia of either myeloid or
      lymphoid tissue of 239Pu exposure.

PMID- 15167127
TI  - Does low dose internal radiation increase lifespan?
AB  - No significant differences in lifespan could be established between control dogs
      and dogs given 241Am, 228Th, 90Sr, 228Ra, 226Ra or monomeric 239Pu at low dosage
      levels that induced less than 10% skeletal malignancies (low dose animals) in the
      Utah beagle colony when all dogs surviving at least 1 y were included in the
      analysis and dogs given individual radionuclides were considered separately or
      together. Censoring or exclusion of dogs from these groups that were diagnosed
      with skeletal malignancies or that died in a gran mal epileptic seizure made no
      important difference to these results. Therefore, an enhanced lifespan of low
      dose dogs as compared with controls could not be established. It is concluded
      that low doses from internal (mainly skeletal) deposits of these radionuclides
      probably do not benefit the survival of individuals so exposed.

PMID- 15167151
TI  - An overview of economic analysis for the practising gastroenterologist and
      hepatologist.
AB  - In this era of limited resources and regulation of health care, it is important
      for the practising clinician to understand the process of economic evaluation of
      health care practices. This review provides an overview of economic analysis for
      the practising gastroenterologist and hepatologist, including information about
      costs and charges, and an explanation of the common types of economic analyses,
      and criteria for critically evaluating economic analyses in the literature.

PMID- 15167152
TI  - Cost-effectiveness analysis and incremental cost-effectiveness ratios: uses and
      pitfalls.
AB  - Cost-effectiveness analysis is a formal method of comparing alternative medical
      interventions with regard to their resource utilization (costs) and outcomes
      (effectiveness). The incremental cost-effectiveness ratio is an informative
      measure generated from such an analysis and represents the ratio of the
      difference in cost between two medical interventions to the difference in
      outcomes between the two interventions. Thus, the incremental cost-effectiveness
      ratio summarizes the additional cost per unit of health benefit gained in
      switching from one medical intervention to another. Although incremental cost
      effectiveness ratios have limitations, when used in the proper context, these
      ratios serve as one of the important tools needed to help guide decisions about
      allocating scarce resources across competing medical programmes.

PMID- 15167153
TI  - Cost-utility and cost-benefit analyses: how did we get here and where are we
      going?
AB  - Cost-utility and cost-benefit analyses are currently the only tools available for
      evaluating whether the cost of an intervention is a good use of resources when
      compared with other ways that money could be spent on health care (allocative
      efficiency). Cost-utility analyses assess health in terms of length and quality
      of life using the quality adjusted life year whilst cost-benefit analyses measure
      health in monetary terms. The measurement of health gain with either approach has
      a number of problems and the accuracy of these measures is uncertain. Cost
      benefit analysis has certain advantages when measuring improvements in mild
      diseases such as irritable bowel disease and dyspepsia, which are common problems
      in gastroenterology. The results of cost-benefit analysis may provide more
      transparent guidance for policy makers, doctors and patients.

PMID- 15167154
TI  - Decision analysis and economic modelling: a primer.
AB  - In this primer, the reader is introduced to the concepts governing decision
      analysis and cost-effectiveness analysis. The construction of decision trees and
      Markov models is presented to provide the necessary background to critique
      research articles in published literature. Specific sub-topics related to cost
      effectiveness analysis are discussed including quality adjustment and utilities
      (patient preferences for health states), discounting, and sensitivity analysis
      including Monte Carlo simulation. Evidence based methods to critique decision and
      cost-effectiveness analysis are provided, and limitations to these analytic
      methods are examined. In summary, the major functions of decision analysis and
      cost-effectiveness analysis are to provide: (1) a quantitative summary of
      existing data, and (2) hypothesis generation for further research.

PMID- 15167155
TI  - Incremental net benefit in the analysis of economic data from clinical trials,
      with application to the CADET-Hp trial.
AB  - In clinical trials it has become increasingly common for cost data to be
      collected in addition to data on clinical effectiveness. In response to this, new
      statistical methodology has been developed. Initially, efforts were focused on
      the incremental cost-effectiveness ratio, but as the problems with ratio
      statistics became apparent, attention was switched to incremental net benefit. In
      this paper statistical methods based on an incremental net benefit approach are
      given and illustrated with an example from the gastrointestinal literature. The
      relationship between incremental net benefit and incremental cost-effectiveness
      is emphasized.

PMID- 15167157
TI  - A glossary of economic terms.

PMID- 15167156
TI  - Statistical approaches to handling uncertainty in health economic evaluation.
AB  - Not so long ago, uncertainty in economic evaluation was handled almost
      exclusively using simple one-way sensitivity analysis methods whereby individual
      parameters of an analysis were varied one-by-one over a range of (often ad-hoc)
      values. With the increasing use of the clinical trial as a vehicle for economic
      evaluation, there has been increasing interest in the use of statistical methods
      for handling uncertainty in patient-level data on both costs and effects.
      However, even for studies based on secondary data, the use of statistical methods
      for specifying parameter distributions in so-called probabilistic analyses is
      becoming increasingly common and is now the method recommended by a number of
      good-practice guides and regulatory agencies. The aim of this paper is to review
      these statistical approaches to the handling of uncertainty, both for primary
      studies where patient level cost and effect information is available and in
      secondary studies that typically use decision analytical methods to synthesize
      summary information from the published literature. The approach throughout the
      paper will be to emphasize the intuition behind the methods rather than the
      technical details. Although the methodology is generally applicable, examples
      will be drawn from both primary and secondary economic evaluations in the area of
      gastroenterology. The first example relates to a primary care trial of dyspepsia
      management which sought to estimate the cost-effectiveness of managing patients
      through early endoscopy compared to usual care. The second example is a secondary
      study of the management of gastro-oesophageal reflux disease symptoms which
      considered six potential strategies simultaneously.

PMID- 15167158
TI  - Nitric oxide and renal function in cirrhotic patients with ascites: from
      physiopathology to practice.
AB  - Patients with cirrhosis and ascites show systemic and splanchnic arterial
      vasodilation, which causes a reduction in effective arterial blood volume and the
      activation of hormonal anti-natriuretic systems. Renal impairment is the most
      important predictor of hospital mortality in cirrhotic patients with SBP. In
      patients with SBP, the inflammatory response to the infection (TNF-alpha, IL-6)
      may be an important mechanism of renal dysfunction. Ascitic-fluid NO metabolites
      are related independently to the development of renal impairment. Treatment of
      SBP with intravenous albumin in addition to cefotaxime prevents renal impairment
      and reduces mortality in comparison with treatment with cefotaxime alone. As soon
      as ascites develops, liver transplantation should be considered in eligible
      patients, especially when local mean waiting times exceed life expectancy. Nitric
      oxide (NO), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)
      have been implicated in the pathogenesis of circulatory alterations observed in
      cirrhotic patients with ascites. Kidney failure is one of the main factors
      associated with mortality in patients with end-stage liver disease developing
      complications, particularly severe infections and variceal haemorrhage. Renal
      impairment occurs in patients with the highest concentration of cytokines in
      plasma and ascitic fluid and is associated with marked activation of the renin
      angiotensin system. In patients with spontaneous bacterial peritonitis (SBP),
      serum and ascitic fluid levels of NO metabolites (nitrites and nitrates) were
      higher than those of patients with sterile ascites, and renal impairment is
      considered to be caused by a decrease in effective arterial blood volume as a
      result of the infection. The administration of albumin prevents deterioration of
      renal function and reduces mortality in these patients. However, SBP and renal
      dysfunction are late complications in the course of liver cirrhosis. As soon as
      ascites develops, liver transplantation should be considered in eligible
      patients, especially when local mean waiting times exceed life expectancy. A
      better knowledge of metabolic disorders associated with the early stage of
      cirrhosis is essential for the development of optimal therapeutic strategies for
      the prophylaxis and treatment of portal hypertension and its complications.

PMID- 15167159
TI  - Nitric oxide in ascitic fluid is an independent predictor of the development of
      renal impairment in patients with cirrhosis and spontaneous bacterial
      peritonitis.
AB  - BACKGROUND/AIMS: Cirrhotic patients with spontaneous bacterial peritonitis show a
      marked activation of the cytokine cascade, and cytokines induce the synthesis of
      nitric oxide in vitro. Our aim was to assess whether patients with ascitic fluid
      infection show increased levels of nitric oxide, and whether this is related to
      the development of renal impairment. METHODS: Retrospective analysis of
      prospectively collected specimens from 168 patients with cirrhosis and presence
      of sterile or infected ascitic fluid. Routine biochemical data together with
      nitric oxide metabolites, tumour necrosis factor and interleukin-6 were measured.
      Univariate and multivariate analyses were performed to identify factors related
      to the development of renal impairment. RESULTS: Patients with infected ascites
      showed increased serum and ascitic-fluid levels of nitric oxide metabolites and
      cytokines compared with patients with sterile ascites. A significant direct
      correlation was observed between serum and ascitic fluid nitric oxide metabolite
      levels. Multivariate analysis identified ascitic-fluid nitric oxide metabolites
      as an independent predictor of renal impairment. CONCLUSIONS: The increased serum
      and ascitic fluid nitric oxide found in patients with infected ascites might
      induce a deterioration of the increased peripheral vasodilation found in this
      setting, leading to the development of renal impairment in a series of patients
      with spontaneous bacterial peritonitis.

PMID- 15167161
TI  - Frequency and predictive factors for overlap syndrome between autoimmune
      hepatitis and primary cholestatic liver disease.
AB  - OBJECTIVES: To evaluate the frequency of cholestatic pattern in patients with
      autoimmune hepatitis (AIH) and to identify predictive factors associated with the
      development of the overlap syndrome. METHODS: Eighty-two consecutive patients
      diagnosed with AIH at the referral centre between January 1998 and June 2002 were
      included in the study. The new scoring system modified by the International
      Autoimmune Hepatitis Group was used to classify patients as definite/probable.
      Overlap syndrome was considered when the patient had clinical, serological and
      histological characteristics of two conditions: AIH and primary biliary cirrhosis
      (PBC) or AIH and primary sclerosing cholangitis (PSC). RESULTS: From the 82 AIH
      patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and
      15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was
      20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap
      syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001),
      histopathological aspect of cholestasis (P < 0.0001), suboptimal response to
      treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable
      AIH and the absence of anti-nuclear antibody (ANA) have been identified as
      independent indicators of the overlap diagnosis by the logistic regression
      analysis. CONCLUSION: Patients with overlap syndrome between AIH and primary
      cholestatic liver disease are frequently diagnosed in clinical practice,
      representing 20% of AIH cases in our study. The independent predictive factors
      associated with the diagnosis of overlap syndrome are young age, ANA(-) profile,
      and probable diagnosis according with the scoring system for AIH.

PMID- 15167160
TI  - Diagnosis of spontaneous bacterial peritonitis in cirrhotic patients by use of
      two reagent strips.
AB  - OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is one of the potentially life
      threatening complications in ascitic cirrhotic patients with a mortality rate
      ranging between 30 and 50%. The improved survival might be explained by a more
      rapid diagnosis and treatment. The aim of our study was to assess the utility of
      two reagent strips, the Multistix test and the Combur(2) test LN, for the rapid
      diagnosis of SBP. METHODS: Thirty-one unselected consecutive cirrhotic patients
      with ascites were included and a total of 100 paracenteses were performed. All
      ascitic fluid was analysed with the two reagent strips, leucocyte and
      polymorphonuclear (PMN) leucocyte cell count and blood-bottle culture if the
      strips were positive. The strips were considered positive if the colour turned to
      purple: i.e. grade 3 or 4 for the Multistix test and 2 or 3 for the Combur(2)
      test LN on a colorimetric scale. RESULTS: We diagnosed nine infections of which
      four were SBP defined by PMN > or = 250 cells/mm(3) and a positive culture in
      ascitic fluid and five were culture negative neutrocytic ascites (PMN > or = 250
      cells/mm(3) and a negative culture). The results of the two strips were
      concordant and were negative in only one SBP. The sensitivity, specificity,
      positive and negative predictive values of these two strips were 89%, 100%, 100%
      and 99%, respectively. CONCLUSIONS: These reagent strips are very sensitive and
      specific for the diagnosis of SBP, allowing immediate commencement of empirical
      antibiotic therapy. These strips should be used for the diagnosis of SBP,
      especially on an emergency basis.

PMID- 15167163
TI  - Validation of the German version of the Chronic Liver Disease Questionnaire.
AB  - OBJECTIVE: The Chronic Liver Disease Questionnaire is an instrument for the
      assessment of health-related quality of life in patients with chronic liver
      diseases. So far it has not been validated for German speaking countries.
      METHODS: Two hundred and three consecutive patients with chronic liver diseases
      (age, 52.7 +/- 13.9 years; 47% female; 45% no cirrhosis, 21% Child's class A, 15%
      Child's class B and 17% Child's class C cirrhosis; 52% with chronic viral
      hepatitis, 32% with alcoholic and 16% with other liver diseases) of a liver
      centre completed the German version of the Chronic Liver Disease Questionnaire
      (CLDQ-D), the Short Form Health Survey SF-36, the Hospital Anxiety and Depression
      Scale (HADS) and the Giessener Symptom List GBB-24. Fifty stable patients filled
      in the CLDQ-D a second time within 3 - 8 days. RESULTS: With 97.7% completed
      items the acceptance by the patients was high. The internal consistency (Cronbach
      alpha) for the subscales ranged from 0.69 to 0.95, the test-retest reliability
      ranged from 0.79 to 0.88. The correlation coefficients with similar subscales of
      the instruments used for validation ranged between 0.5 and 0.9 (convergent
      validity). Patients with liver cirrhosis Child-Pugh stage C scored significantly
      lower in the subscales 'Abdominal Symptoms', 'Activity' and 'Worry', indicating a
      reduced health-related quality of life than in patients without cirrhosis (P <
      0.05) (discriminant validity). CONCLUSION: The CLDQ-D is well accepted by
      patients with chronic liver diseases and has good reliability and satisfactory
      discriminant validity.

PMID- 15167164
TI  - Application of the model for end-stage liver disease score for transjugular
      intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites
      and renal impairment.
AB  - BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) can
      manage severe complications of portal hypertension. The Mayo Clinic group
      proposed a so-called model for end-stage liver disease (MELD) to predict survival
      in cirrhotic patients. High creatinine levels determine a decrease in calculated
      survival chances with MELD but functional renal disease can be reversed by TIPS.
      The aim of this study was to evaluate the efficacy of MELD in predicting survival
      after TIPS, particularly in patients with refractory ascites associated with
      functional renal failure. METHODS: This retrospective analysis examines 68
      cirrhotic patients who underwent elective TIPS: 48 patients had refractory
      ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis
      was used to establish predictive parameters of survival after TIPS. Kaplan-Meier
      and log-rank tests were used to compare survival rates observed in our patients
      with those evaluated with the MELD score. RESULTS: The age of patients was the
      only variable shown to have an independent value in predicting survival after
      TIPS. In patients undergoing shunting for refractory ascites, the survival rates
      at 6, 12 and 24 months after the procedure were significantly higher than
      expected with the MELD score. CONCLUSIONS: The MELD scale may underestimate the
      efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and
      functional kidney dysfunction. Further studies are needed to confirm this finding
      and ultimately to assess a correction factor to better predict survival after
      TIPS in patients with functional renal impairment.

PMID- 15167162
TI  - Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing
      liver steatosis: the role of glucose intolerance.
AB  - OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast
      cancer patients with pre-existing liver steatosis. The aim of our study was to
      investigate the most common predisposing factors for non-alcoholic fatty liver
      disease in breast cancer patients with liver steatosis, treated with adjuvant
      tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen
      induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an
      oral glucose tolerance test, was done in 60 women with breast cancer and liver
      steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months
      during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver
      function tests during tamoxifen treatment whereas these test results were below
      the normal range at baseline control. Statistical evaluation of data was
      performed using parametric methodology (the chi-squared test, and Student's t
      test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced
      hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall
      follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120
      months) and did not differ between the two groups (P = 0.055). There was
      significant statistical difference in body mass index (BMI) and baseline fasting
      glucose, cholesterol and triglyceride levels between the two groups. Eighteen of
      26 patients (69.2%) from group A had impaired glucose tolerance compared with
      only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in
      BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002).
      CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion
      of breast cancer patients with pre-existing liver steatosis, especially those
      with higher BMI and higher glucose and lipid levels at baseline control. Glucose
      intolerance before the beginning of tamoxifen treatment seems to be a predictor
      of the hepatotoxicity, unrelated to baseline BMI.

PMID- 15167165
TI  - Colonic regular contractile frequency patterns in irritable bowel syndrome: the
      'spastic colon' revisited.
AB  - BACKGROUND: Irritable bowel syndrome is a frequent gastrointestinal disorder of
      which the pathophysiological basis is still not completely understood. Among the
      various proposed mechanisms, colonic motility may play a role, at least in a
      subset of patients. AIMS: To investigate the regular colonic contractile patterns
      in patients with irritable bowel syndrome. Our working hypothesis was that an
      increase of these patterns in such condition might represent a motility
      equivalent of the so-called 'spastic colon'. PATIENTS AND METHODS: Twelve
      patients of both genders were investigated by means of 24 h colonic manometry,
      and the results were compared to those from 20 healthy controls. Regular
      contractile patterns (with frequencies ranging from 2 to 8 per min) were
      calculated for the entire recording period and in single colonic segments.
      RESULTS: Overall, colonic frequency patterns were significantly more frequent in
      patients than controls (12.6% vs 6.4% of the total contractile activity, P <
      0.001); in both groups, the 3 cycles/min frequency was predominant, especially in
      the sigmoid colon. More than 40% patients displayed a correlation between
      abdominal pain and occurrence of regular contractile frequencies. CONCLUSIONS:
      Abnormal colonic motility may play some role in the pathogenesis of symptoms
      related to irritable bowel syndrome, with an excess of regular contractile
      activity related to the so-called 'spastic colon'.

PMID- 15167166
TI  - The relationship between cyclooxygenase-2 expression and characteristics of
      malignant transformation in human colorectal adenomas.
AB  - BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) is a target of aspirin and other
      non-steroidal anti-inflammatory drugs and is implicated in the pathogenesis of
      colorectal cancer. The objective of this study was to evaluate the extent of COX
      2 in pre-malignant colorectal polyps and to assess the relationship between COX-2
      and the level of dysplasia in these lesions. METHODS: Whole polypectomy specimens
      were retrieved from 123 patients by endoscopic or surgical resection. Following
      formalin fixation and paraffin embedding, the polyps were evaluated
      histologically for size, type and grade of dysplasia. The extent of COX-2
      expression was measured by the avidin-biotin immunohistochemical technique using
      a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according
      to percentage epithelial COX-2 expression. RESULTS: The polyps were of the
      following histological types: 10 hyperplastic, 35 tubular adenomas, 61
      tubulovillous adenomas and 17 villous adenomas. Twenty showed mild dysplasia, 65
      moderate dysplasia, and 28 focal or severe dysplasia (including eight with focal
      invasion). The average polyp size was 1.7 cm. Nine hyperplastic polyps were COX-2
      negative and one was COX-2-positive. COX-2 expression was more extensive in
      larger polyps and in polyps with a higher villous component. There was a
      significant increase in the extent of COX-2 protein with increasing severity of
      dysplasia. Within a polyp, there was a focal corresponding increase in COX-2
      expression within epithelium showing a higher grade of dysplasia. CONCLUSIONS:
      COX-2 expression is related directly to colorectal adenomatous polyp size, type
      and grade of dysplasia. This suggests that the role of COX-2 in colorectal cancer
      may be at an early stage in the adenoma-to-carcinoma sequence and supports the
      suggestion that inhibition of COX-2 may be useful chemoprevention for this
      disease.

PMID- 15167167
TI  - Severe anaphylactic reaction to infliximab: successful treatment with adalimumab 
      report of a case.
AB  - Treatment with the anti-tumour necrosis factor alpha chimeric monoclonal antibody
      infliximab is highly effective in the treatment of refractory and fistulising
      Crohn's disease. Infliximab has been tolerated well, with minimal and short-lived
      adverse effects. The likelihood of severe reactions to infliximab, such as acute
      and delayed hypersensitivity infusion reactions, is small; nevertheless, if they
      do occur, they are life-threatening. We report a case of an anaphylaxis-like
      reaction in a 22-year-old female with long-standing Crohn's disease. The patient
      was treated successfully with adalimumab, a fully human anti-tumour necrosis
      factor alpha monoclonal antibody. Follow-up demonstrated mucosal healing and
      normalisation of elevated pro-inflammatory cytokine transcripts.

PMID- 15167168
TI  - Changes.

PMID- 15167169
TI  - Who calls for the ambulance: implications for decision support. A descriptive
      study from a Swedish dispatch centre.
AB  - The dispatcher plays a key role in allocating the right resource to patients in
      cases of medical emergency. In order to evaluate the performance of the
      dispatcher, it is necessary to analyse who is the caller, because this has an
      impact on the development of decision support systems. In the present study, all
      calls for an ambulance (n=565) during a one-week period at the dispatch centre in
      Uppsala, Sweden, were analysed with respect to the caller's relationship to the
      patient, the location of the caller, and the dispatcher's priority of the case.
      In emergencies, significantly fewer calls were made by the patients themselves,
      and significantly more callers had no relationship to the patient. In low
      priority cases most calls were made by healthcare providers. During a 2-week
      period we also analysed the physiological impairment of patients in cases
      dispatched as medical emergencies (n=595) by using the rapid acute physiological
      score. The rapid acute physiological score was significantly higher in the group
      dispatched as potentially life-threatening by the dispatcher compared with other
      emergencies. The study highlights the fact that dispatching often has to be
      carried out using second or third-hand information, and those patients
      prioritized as suffering from potentially life-threatening conditions have a more
      impaired physiological status.

PMID- 15167170
TI  - The use of automated external defibrillators by non-medical first responders in
      Finland.
AB  - OBJECTIVE: To assess the spread of automated external defibrillators and their
      use by non-medical first responders in Finland. METHODS: A structured survey was
      mailed to all voluntary and ordinary fire brigades in Finland. The questions were
      related to the purchase, experience of use and anticipated benefits from the
      devices. RESULTS: Approximately 90% of all users (133 providers) in the target
      group of non-medical first responders answered. The number of automated external
      defibrillators in use by these operators has increased progressively since 1992.
      Most respondents possessed only one automated external defibrillator, and a
      median of 12 users were trained to use each device. A total of 85% of the
      respondents retrained at least once a year, and 94% checked the device on a daily
      basis. Half of the users had written authorization to use the automated external
      defibrillator, and two thirds had written instructions on how to operate it. Each
      automated external defibrillator was used on average five to 10 times annually.
      Although none of the respondents could provide data on how many cardiac arrests
      they had attended or the success of resuscitation during the preceding year, 94%
      reported that they considered the automated external defibrillator useful, and
      80% thought that the cost-benefit of the device was either very good or good.
      CONCLUSION: Although there are many automated external defibrillators in use by
      non-medical first responders in Finland, the results of this study show that
      there are large variations between individual fire brigades regarding the use of
      these devices as part of the first response system. This is considered to be
      caused by the lack of national standards and regulations, which should define a
      full integration of first-responder programmes into the emergency medical service
      system.

PMID- 15167171
TI  - Variations in pre-hospital fibrinolysis process of care: insights from the
      Assessment of the Safety and Efficacy of a New Thrombolytic 3 Plus international
      acute myocardial infarction pre-hospital care survey.
AB  - The Assessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3 PLUS)
      Plus trial (n=1639) was an international trial of pre-hospital fibrinolysis with
      tenecteplase randomly assigned to enoxaparin or unfractionated heparin, involving
      106 sites in 12 countries. Given the potential impact of process of care delivery
      in various healthcare systems, we undertook a comprehensive validated survey of
      population demographics, geographical factors, emergency medical services,
      methods of electrocardiogram interpretation and pre-hospital fibrinolysis
      administration. The potential study population was 42.4 x 10(6) with 70% urban.
      The land areas of individual emergency medical services sites varied from 6 to
      20000/km(2). Three emergency medical services personnel (range 2-5) attended each
      ambulance with the highest level of training, consisting of a physician (65%),
      registered nurse (20%) or paramedic. Before the initiation of the study, 72% of
      sites administered pre-hospital fibrinolysis (range 1-20 years).
      Electrocardiograms were interpreted on the scene in 60% and transmitted for
      physician's interpretation in the remainder; 41% of patients (679/1639) were
      enrolled at sites without a physician at the scene. The ASSENT 3 Plus trial
      incorporated a wide variation in population density, emergency medical services
      resources, and physician's interpretation of ECG and administering pre-hospital
      fibrinolysis. Understanding this diversity will help in evaluating the general
      applicability and feasibility of pre-hospital fibrinolysis in various health
      systems, as well as the pre-hospital care of ST elevation myocardial infarction
      patients regardless of reperfusion strategies.

PMID- 15167172
TI  - Discharge from the accident and emergency department after smoke inhalation:
      influence of clinical factors and emergency investigations.
AB  - OBJECTIVES: Smoke inhalation has become the principal cause of death in burns
      patients. There are few guidelines for the management of smoke inhalation in the
      accident and emergency department. The aim was to identify what factors influence
      immediate management. METHODS: A retrospective case note review using data from
      three west of Scotland accident and emergency departments in 1999. Computerized
      record systems were used to identify suitable patients. RESULTS: Of 120 patients,
      63 patients had incomplete data and were excluded. A total of 57 patients were
      classified into one of five categories: no burns, normal vital signs and
      examination (group 1, n=23); no burns, abnormal vital signs or examination (group
      2, n=26); minor burns (<15% total body surface area) with or without abnormal
      vital signs or examination (group 3, n=5); major burns (>15% total body surface
      area) (group 4, n=2); in cardiac arrest on arrival (group 5, n=1). In groups 1
      and 3, the result of two investigations significantly influenced management. In
      group 2, arterial blood gases and carboxyhaemoglobin levels were abnormal in 25%
      of cases, but only on one occasion did it influence an admission decision.
      CONCLUSION: Arterial blood gases, chest radiography and carboxyhaemoglobin
      estimation rarely influence immediate management. Patients presenting with normal
      vital signs and examination and short smoke exposure may be safe to discharge
      from the accident and emergency department without further investigation.

PMID- 15167174
TI  - Microscooter injuries in the paediatric population.
AB  - OBJECTIVES: To illustrate the types of injuries seen by the accident and
      emergency department as a result of the use of non-motorized 'microscooters' in
      children, and to increase awareness of scooter-related triplane fractures of the
      ankle. STUDY DESIGN: A retrospective study conducted in an accident and emergency
      department of a district general hospital on all children who had a scooter
      related limb injury over a 6-month period and were referred for orthopaedic
      review. METHODS: The analysis involved a case note review. Information recorded
      included the injury sustained, protective equipment worn at the time of the
      accident and management by the orthopaedic team. RESULTS: Scooter injuries
      accounted for 10 fractures in this period. There were three 'triplanar' injuries,
      which required operative fixation, and three injuries requiring manipulation
      under anaesthesia. No protective gear was worn by any of the patients.
      CONCLUSION: The popularity of microscooters seems to represent a significant risk
      of bony injury in the paediatric population. Medical personnel who manage acute
      paediatric trauma should be aware of scooter-related triplanar ankle injuries.

PMID- 15167173
TI  - Traumatic haemarthrosis of the knee.
AB  - BACKGROUND: Haemarthrosis of the knee after trauma is a common problem often seen
      in accident and emergency departments. OBJECTIVE: : To evaluate the injuries
      sustained after haemarthrosis of the knee in a relatively young population, and
      to assess the need for performing cultures on aspirated blood. PATIENTS AND
      METHODS: The notes of 510 patients who were seen at the accident and emergency
      department of the Alexandra Hospital, Redditch, between 1990 and 1999 were
      retrospectively studied. The age, sex, mechanism of injury, final diagnosis and
      management were recorded. The exact diagnosis was confirmed by a magnetic
      resonance imaging scan or arthroscopy findings. All the patients had their knee
      aspirate cultured, and the reports on the culture of aspirated blood were
      obtained from the department of pathology. RESULTS: A fall was the major cause of
      haemarthrosis in 52%, followed by sports injury in 38%. The medical records of
      all 510 patients were reviewed. All patients' follow-up records were seen, most
      patients were followed up in the orthopaedic outpatient clinic and some in the
      accident and emergency follow-up clinic, all attended at least three or more
      clinics before discharge. CONCLUSION: Culture of the aspirate of all patients was
      felt to be a waste of time and money. Nearly 40% of cases were thought to be
      idiopathic and settled conservatively without intervention.

PMID- 15167175
TI  - Convective air warming is more effective than resistive heating in an
      experimental model with a water dummy.
AB  - Trauma patients with accidental hypothermia have adverse outcomes when compared
      with normothermic patients. Studies with a small number of mild hypothermic
      volunteers suggested that convective warming is more effective than warming with
      12 volt resistive heating blankets. In a laboratory study, we compared the
      warming effectiveness of two electric blankets and convective air warming. The
      average speed of convective rewarming during anaesthesia in patients is
      approximately 0.6 degree C per hour. Accordingly, calibration of the dummy was
      performed with increasing amounts of water during convective warming until we
      reached a temperature gain of 0.6 degree C per hour. The following warming
      experiments were performed: 12 volt electric warming blanket (SH6012, Hella); 12
      volt electric warming blanket (Thermamed, whole-body blanket); convective air
      warming (Warm Touch, Mallinckrodt, whole-body blanket). Each experiment was
      repeated four times. The temperature development was measured and recorded
      online. Convective warming increased the dummy temperature 0.6 degree C per hour,
      Thermamed 0.3 degree C per hour (P<0.001 versus convective warming) and two Hella
      blankets 0.2 degree C per hour (P<0.001 versus convective warming). Our
      laboratory investigation confirmed the superiority of convective warming over
      resistive heating. Efforts should be made to incorporate convective warming into
      the out-of-hospital treatment of trauma patients.

PMID- 15167176
TI  - Is the 'LEMON' method an easily applied emergency airway assessment tool?
AB  - OBJECTIVE: To assess whether the 'LEMON' method, devised by the developers of the
      US National Emergency Airway Management Course, is an easily applied airway
      assessment tool in patients undergoing treatment in the emergency department
      resuscitation room. METHODS: One hundred patients treated in the resuscitation
      room of a UK teaching hospital between June 2002 and January 2003 were assessed
      on criteria based on the 'LEMON' method. RESULTS: All seven criteria of the
      'Look' section of the method could be adequately assessed. Data for the
      'Evaluate' section could not be obtained in 10 patients, with inter-incisor
      distance being the most problematical item. The 'Mallampatti' score was
      unavailable in 43 patients, and had to be assessed in the supine position in 32
      of the remaining 57 patients. Assessment for airway 'Obstruction' and 'Neck
      mobility' could be performed in all patients. CONCLUSION: The 'Look',
      'Obstruction' and 'Neck mobility' components of the 'LEMON' method are the
      easiest to assess in patients undergoing treatment in the emergency department
      resuscitation room. The 'Evaluate' and 'Mallampatti' components are less easily
      applied to the population that present to the resuscitation room, and assessment
      of these is more problematical and prone to inaccuracy. We suggest that the
      'LEMON' airway assessment method may not be easily applied in its entirety to
      unselected resuscitation room patients, and that information on the 'Evaluate'
      and 'Mallampatti' parameters may not always be available.

PMID- 15167177
TI  - Is measurement of capillary refill time useful as part of the initial assessment
      of children?
AB  - OBJECTIVE: The purpose of this study was to establish the usefulness of capillary
      refill time when measured during the initial assessment of children. METHODS: All
      children with spontaneous illness attending a paediatric accident and emergency
      department over a 7-month period were eligible for entry into the study.
      Capillary refill time was measured at the fingertip, using a standard technique,
      as part of the initial assessment. Each child was then followed up to ascertain
      clinical progress, including the need for admission, intravenous fluids, length
      of stay and diagnosis, as well as the white cell count when this was available.
      The value of capillary refill time as a predictor of the markers of illness
      severity was then assessed. RESULTS: Capillary refill time measurements were
      recorded on 4878 children. There was no significant association of capillary
      refill time with meningococcal disease, other significant bacterial illness or
      the white cell count. A prolonged capillary refill time was associated with a
      more urgent triage category, the administration of a fluid bolus and the length
      of hospital stay (P<0.0001). The best performance was obtained when a capillary
      refill time of 3s or more is taken to be 'prolonged'. However, this gave positive
      predictive values of only 9% for a triage category of 1 or 2 (negative predictive
      value 97%), 11% for requiring a fluid bolus (negative predictive value 99%), 55%
      for hospital admission (negative predictive value 65%) and 22% for stay over 2
      days/death (negative predictive value 91%). CONCLUSION: The prolongation of
      capillary refill time is a poor predictor of the need for intravenous fluid bolus
      or hospital admission.

PMID- 15167179
TI  - Brachial plexus lesion following an anterior dislocation of the shoulder.

PMID- 15167178
TI  - Bilateral adrenal haemorrhage and acute adrenal insufficiency in a blunt
      abdominal trauma: a case-report and literature review.
AB  - Blunt abdominal trauma is frequently associated with adrenal haemorrhage, and is
      preferentially diagnosed by computed tomography scan. Lesions are mostly
      unilateral and asymptomatic and are therefore frequently overlooked. Bilateral
      haemorrhage, however, has a high mortality rate as a result of acute adrenal
      insufficiency. We report on a 30-year-old polytraumatic patient who developed
      cardiocirculatory arrest when all lesions were surgically controlled and stable
      and without evidence of a primary cardiac problem. Autopsy revealed bilateral
      adrenal haemorrhage, leading to the diagnosis of acute adrenal insufficiency as
      the cause of death. We conclude that adrenal haemorrhage should be looked for in
      every polytrauma patient, and that although it is a rare occurrence, acute
      adrenal insufficiency caused by bilateral adrenal haemorrhage should be
      considered in every patient with unexplained cardiocirculatory failure. Such
      patients may benefit from the prompt administration of corticosteroid
      replacement, which can be life saving.

PMID- 15167180
TI  - Vertical patellar dislocation: a case report.
AB  - Dislocation of the patella around the vertical axis is rare. Previous reports
      suggest reduction requires general anaesthesia and occasionally open reduction is
      necessary. We describe a case of dislocation of the patella around its vertical
      axis with impaction in the intercondylar notch of the femur following minor
      trauma. Successful reduction was achieved without the need for general
      anaesthesia.

PMID- 15167181
TI  - Ketosis and cardiac failure: common signs of a single condition.
AB  - The metabolic effects of chronic alcohol abuse can induce a broad spectrum of
      disorders. We describe the case of an initially unidentified alcoholic, poorly
      nourished woman who presented with ketoacidosis. She developed severe cardiac
      failure, which did not respond to classical treatment. The administration of
      intravenous thiamine resulted in an impressive recovery of cardiac function.
      Laboratory examinations confirmed the diagnosis of alcoholic ketoacidosis and
      cardiac beriberi. The clinical entity and treatment of these two uncommon
      disorders are discussed. If recognized early both diseases (and their
      combination) are fully reversible.

PMID- 15167182
TI  - Abdominal pain in varicella: an unusual cause of spontaneous splenic rupture.

PMID- 15167183
TI  - Stroke in young patients: a diagnostic challenge in the emergency room.
AB  - Stroke in young adults has been related to mechanisms different to those found in
      older individuals. Cardiogenic embolism, arteritis, atherosclerosis,
      fibromuscular dysplasia, pregnancy-related angiopathy, migrainous stroke,
      anaemia, antiphospholipid syndrome, arterial dissection, the consumption of toxic
      substances and head trauma have been described. We present a young man with a
      case history of tobacco and cocaine abuse who suffered a mild head trauma, with
      normal neurological examination, and a computed tomography scan image of a right
      anterior cerebral infarction. Serum biochemistry showed no alterations according
      to the diagnosis protocol for stroke in young patients. Various mechanisms have
      been involved, such as vasospasm, increasing arterial pressure and embolism.
      Considering the cocaine abuse and the mild head trauma, in our patient vasospasm
      was thought to be the mechanism involved in the cerebral infarction, which proved
      a challenge to diagnose in the emergency room.

PMID- 15167184
TI  - Spontaneous tension pneumopericardium.
AB  - A 29-year-old man presented to the accident and emergency department complaining
      of a sudden onset of chest and upper abdominal pain. He had a past history of
      intravenous drug abuse and a previous stab wound to the left hypochondrium that
      had required laparotomy. On arrival he was distressed with grunting respiration.
      Initial chest X-ray showed a pneumopericardium. Despite titrated doses of opiate
      analgesia he became increasingly distressed, agitated and dyspnoeic. Repeat chest
      X-ray demonstrated an increase in the volume of air present within the
      pericardial sac. His clinical condition improved rapidly after needle
      pericardiocentesis decompression. A water-soluble contrast swallow revealed a
      diaphragmatic hernia with a filling defect in the greater curve of the stomach
      and contrast medium entering the pericardial sac. A thoraco-abdominal laparotomy
      confirmed a pre-existing diaphragmatic defect from the previous stab wound, with
      surrounding adhesions. A small portion of the stomach had herniated through this
      defect with a perforated gastric ulcer communicating directly into the
      pericardial sac.

PMID- 15167185
TI  - Syndromic surveillance.

PMID- 15167186
TI  - Real-time syndrome surveillance in Ontario, Canada: the potential use of
      emergency departments and Telehealth.
AB  - OBJECTIVE: The purpose of this paper is to review new bioterrorist and emerging
      infectious threats to public health in Ontario, Canada, and to propose a means of
      integrating a telephone-based health information service and emergency department
      triage with a first-line real-time, 24-h a day syndrome surveillance system. This
      automated system could be beneficial in detecting a bioterrorist threat as well
      as in detecting and monitoring disease outbreaks such as influenza, Norwalk, West
      Nile virus, Escherichia coli 0157 or severe acute respiratory syndrome. METHOD:
      The Medline PubMed database was searched for articles relating to bioterrorism
      and syndromic surveillance from 1997 onwards. The websites of the Ontario
      Ministry of Health and Long-Term Care, Ontario Ministry of Public Safety and
      Security, Centers for Disease Control and Canadian Population and Public Health
      Branch of Health Canada were searched for articles relating to bioterrorism and
      syndromic surveillance. Interviews were conducted with key informants from
      Telehealth staff, the public health services of Ontario and the Centers for
      Disease Control and Prevention, Atlanta, GA, USA. RESULTS: Real-time syndrome
      surveillance is a new means of detecting disease outbreaks or possibly acts of
      bioterrorism at the first contact with the healthcare system. It has been used
      successfully to detect influenza outbreaks at an early stage. The system that is
      proposed would be a province-wide integrated early warning system for both
      bioterrorist events and emerging infections. It would use clusters of symptoms
      tied to temporal, demographic and spatial data to increase sensitivity and
      specificity. CONCLUSION: Real-time syndrome surveillance is an evolving science.
      Emergency departments and Telehealth in Ontario lend themselves as first contacts
      to the healthcare system as excellent opportunities to perform syndrome
      surveillance. They offer the opportunity properly to identify at-risk patients
      for emerging infections by including contact and travel data into the symptom
      complex. This could identify at-risk patients early and lead to appropriate
      public health measures. The benefit of using Telehealth in Ontario is the
      provincial accessibility of Telehealth and the extensive data collected on one
      computerized system. Emergency departments should also have a uniform
      computerized triage data collection system to facilitate surveillance.

PMID- 15167187
TI  - Beneficial effects of direct call to emergency medical services in acute
      myocardial infarction.
AB  - OBJECTIVES: We investigated the impact of an emergency medical services call on
      the management of acute myocardial infarction, considering time intervals for
      intervention and revascularization procedures. METHODS: Data were prospectively
      collected from January 2001 to October 2002 from 531 patients hospitalized for
      myocardial infarction with ST segment elevation and a pre-hospital delay of less
      than 24 h. RESULTS: Only 26% of patients called the emergency medical services at
      the onset of symptoms (n=140). Other patients (n=391, 74%) called another medical
      contact. Baseline characteristics and cardiovascular history were similar in the
      two groups, except for the percutaneous coronary intervention history (10% in the
      emergency medical services group versus 4% in the other medical contact group,
      P<0.05). Time intervals from the onset of symptoms of myocardial infarction to
      call or to medical intervention, as well as the time interval from medical
      intervention to hospital admission were significantly shorter in the emergency
      medical services group. The early reperfusion rate was also significantly greater
      in the emergency medical services group (77%) compared with the other medical
      contact group (64%), mainly because of a greater incidence of primary
      percutaneous coronary intervention (36 versus 26%, P<0.03, respectively).
      Multivariate analysis adjusted for sex and age showed that less than three
      medical care providers [odds ratio (OR) 5.042, P<0.001], percutaneous coronary
      intervention history (OR 2.462, P<0.05), as well as rhythmic disorders (OR 2.105,
      P<0.05) and complete atrioventricular block (OR 2.757, P<0.05) were independent
      predictors of emergency medical services care. CONCLUSION: This study
      demonstrated that a call to the emergency medical services is underutilized by
      patients with symptoms of myocardial infarction, and documented the beneficial
      effects of an emergency medical services call by reducing pre-hospital delays and
      increasing early revascularization therapies.

PMID- 15167188
TI  - Adverse events after naloxone treatment of episodes of suspected acute opioid
      overdose.
AB  - OBJECTIVE: An increasing and serious heroin overdose problem in Oslo has mandated
      the increasing out-of-hospital use of naloxone administered by paramedics. The
      aim of this study was to determine the frequencies and characteristics of adverse
      events related to this out-of-hospital administration by paramedics. METHODS: A
      one-year prospective observational study from February 1998 to January 1999 was
      performed in patients suspected to be acutely overdosed by an opioid. A total of
      1192 episodes treated with naloxone administered by the Emergency Medical Service
      system in Oslo, were included. The main outcome variable was adverse events
      observed immediately after the administration of naloxone. RESULTS: The mean age
      of patients included was 32.6 years, and 77% were men. Adverse events suspected
      to be related to naloxone treatment were reported in 45% of episodes. The most
      common adverse events were related to opioid withdrawal (33%) such as
      gastrointestinal disorders, aggressiveness, tachycardia, shivering, sweating and
      tremor. Cases of confusion/restlessness (32%) might be related either to opioid
      withdrawal or to the effect of the heroin in combination with other drugs.
      Headache and seizures (25%) were probably related to hypoxia. Most events were
      non-serious. In three episodes (0.3%) the patients were hospitalized because of
      adverse events. CONCLUSION: Although adverse events were common among patients
      treated for opioid overdose in an out-of-hospital setting, serious complications
      were rare. Out-of-hospital naloxone treatment by paramedics seems to save several
      lives a year without a high risk of serious complications.

PMID- 15167189
TI  - Anticipating events of in-hospital cardiac arrest.
AB  - STUDY OBJECTIVES: To determine whether in-hospital cardiac arrests occurring in
      regular wards are preceded by some event(s), and the diagnostic and therapeutic
      measures adopted. METHODS: From 1 May 1999 to 31 December 2001, events occurring
      in the 6 h preceding cardiac arrest were reviewed by checking the medical and
      nurse records and interviewing the attending staff. Exclusion criteria were (a)
      location in the Coronary Care Unit, the Intensive Care Unit, the Emergency
      Department and the operating rooms; (b) the presence of rapidly fatal disease;
      (c) the lack of adequate documentation. RESULTS: Overall, 263 cardiac arrests
      occurred in the period under consideration. A total of 148 patients (61 women, 87
      men, aged 74.3+/-1.2 years) fulfilled the entry criteria. Anticipating events
      were reported in 128 patients (86.4%). These included alterations in
      consciousness, cardiac arrhythmias, dyspnoea and chest pain. The restoration of
      cardiac rhythm was obtained in 23 patients (15.5%). Eight (5.4%) survived without
      major neurological sequelae. Survivors were significantly younger than non
      survivors (survivors 44.3+/-6.8 years; non-survivors 76.7+/-2.1 years; P<0.005).
      In a substantial number of cases, ranging from 23 to 81%, according to the
      anticipating event, no diagnostic investigations were performed. CONCLUSION: Most
      in-hospital cardiac arrests are preceded by events that often go overlooked and
      whose correct interpretation could be associated with a reduced mortality rate.

PMID- 15167190
TI  - Reduced length of stay in medical emergency department patients: a prospective
      controlled study on emergency physician staffing.
AB  - OBJECTIVE: Patients, emergency department staff and hospital managers are often
      confronted with a prolonged length of stay of emergency department patients, with
      resulting overcrowding in the emergency department. We hypothesized that
      additional medical personnel would reduce the length of stay. METHODS: We
      prospectively studied consecutive patients managed in a medical emergency
      department by internal medicine residents during the evening shift. Data were
      collected on patients managed before (n=200) and after (n=160) the addition of a
      second physician on the shift. RESULTS: The addition of a physician in the busy
      evening shift decreased the length of stay from 176+/-137 to 141+/-86 min (mean+/
      SD, P=0.012) for outpatients discharged after evaluation and management in the
      emergency department. The length of stay for emergency department inpatients
      admitted for hospitalization was not significantly reduced. CONCLUSION: An
      additional physician significantly reduced the length of stay of medical
      emergency department outpatients.

PMID- 15167191
TI  - Universal screening for interpersonal violence: inability to prove universal
      screening improves provision of services.
AB  - OBJECTIVE: Universal screening for interpersonal violence is recommended despite
      a lack of confirmed efficacy. We hypothesized that the detection of violence via
      universal screening would result in high intervention rates for victims. METHODS:
      Women aged 18-65 years presenting to an emergency department were screened using
      a standard protocol. Medical and social work records were reviewed for positively
      screened patients. Outcomes included whether victims received counseling/referral
      services. Secondary outcomes were the documentation of services offered and
      safety assessment performed. RESULTS: A total of 1732 patients were evaluated;
      615 (35.5%) responded positively to at least one query. Patients had a mean age
      of 34.7+/-12 years, 79% were non-white, 19% were married, and 76% had completed
      high school. Twenty-five out of 606 victims (4%) had documentation of violence.
      Residents were more likely than faculty or nurses to document domestic violence
      [3.3% (95% confidence interval 1.8-4.8%) versus 2.1 (0.9-3.4) versus 0.7 (0.0
      1.4)]. The documentation of police contact, suicide/homicide risk, weapon
      presence, safety assessment and outside resource referrals occurred in less than
      2% of charts. Only two victims were referred to social work (0.3%; 0-0.9%).
      CONCLUSION: Even in an institution with a heavy emphasis and training on
      interpersonal violence and alternative mechanisms for universal screening we
      could not prove that the identification of victims resulted in
      counseling/referral being offered in the emergency department.

PMID- 15167192
TI  - Medical care at the VIIth International Amateur Athletics Federation World
      Championships in Athletics 'Sevilla '99'.
AB  - INTRODUCTION: The World Athletics Championships are considered to be the third
      most important sporting event on the planet. Before the celebration of their
      seventh meeting in Seville, Spain, the need for medical care, as in the Olympic
      Games, was supposed to be low and of minimal complexity. It was nevertheless
      judged necessary to install strategically located assistance points, and to
      evaluate the results of this intervention. METHODOLOGY AND DESIGN: Following the
      planning phase carried out by a multidisciplinary commission of health, set up by
      the Organizer Committee, which prepared protocols, that were elaborated by five
      working groups, the operation developed during the World Championships in
      Athletics is described. Five clinics and several first aid stations were set up
      in the stadium and its surroundings, in hotels, warm-up and training tracks, the
      high-speed train station and the airport, as well as strategic points in the
      city. RESULTS: There were 1338 medical consultations, and 35 patients (2.6%) were
      transferred to hospitals. 21 codes of the International Classification of Disease
      constituted 50.4% of the case mix. Injuries, which accounted for 36.1% of all
      medical visits, were more common among athletes (48.9%) than among other groups.
      Injuries accounted for 30.5% of all other groups combined. Spectators and other
      groups accounted for most (86.8 and 63.1%, respectively) of the 276 visits
      concerning contusions and 165 visits for heat-related illness. The overall
      physician treatment rate was 19.3% for athletes and 4.5/10 000 for spectators.
      CONCLUSION: The preparation of a potent pre-hospital service, strategically
      located and dedicated to the event, was able to solve the problems that occurred.
      Nevertheless, a hospital alert and a coordination centre are also necessary.
      These data should be useful in planning medical resources for future mass
      sporting events.

PMID- 15167193
TI  - Necrotizing fasciitis: a dramatic surgical emergency.
AB  - OBJECTIVES: Necrotizing fasciitis is a challenging and potentially lethal
      disease; early diagnosis is of paramount importance and aggressive
      multidisciplinary treatment is mandatory. Overall mortality rates of 33-73% have
      been reported. The aim of this study was to report the experience with
      necrotizing fasciitis of an emergency surgery department. METHODS: From October
      1995 to December 2001 we observed 11 cases of necrotizing fasciitis. The patients
      were five men and six women, with ages ranging from 33 to 80 years. RESULTS:
      Triggering aetiological factors were found in eight cases. In all patients a
      multidisciplinary approach was utilized. Every patient had a daily surgical
      debridement of the necrotic areas in the operating room. Polyantibiotic therapy
      was performed, and was changed according to culture results. After surgery, nine
      patients were submitted to hyperbaric oxygen therapy. Seven deaths (63.6%) were
      observed: two cases of pulmonary embolism and five cases of septic shock. Four
      patients survived; three had a complete recovery with progressive healing of the
      wounds, whereas one patient had severe impairment of the motility of the affected
      hand. The mean interval between the onset of symptoms and hospital admission was
      5.4 days; for patients who ultimately died it was 7.3 days, whereas for patients
      who ultimately survived it was 2 days (P<0.05); moreover these patients were
      significantly younger than those who died (P<0.05). CONCLUSION: The treatment for
      necrotizing fasciitis is a combination of surgical debridement, appropriate
      antibiotics and optimal oxygenation of the infected tissues. However, the
      mortality for this disease is quite high, and is related to late diagnosis and
      advanced age. Necrotizing fasciitis must be considered a true dramatic surgical
      emergency.

PMID- 15167194
TI  - Necrotizing fasciitis of the leg presenting with chest wall emphysema.
AB  - We present the case of a 70-year-old woman with necrotizing fasciitis of the
      right leg, sepsis and bacteraemia with Escherichia coli. Chest wall emphysema,
      detected on standard radiograph and the presence of air in the soft-tissue of the
      foot was the reason for prompt surgical drainage in addition to standard fluid
      resuscitation and antibiotic therapy. There was no evidence of underlying
      diabetes mellitus, but unknown chronic renal failure and corticosteroid therapy
      for rheumatoid arthritis were considered predisposing factors. We present a short
      overview of this rare life-threatening condition with emphasis on radiological
      diagnostic modalities.

PMID- 15167195
TI  - Stridor after ingestion of dettol and domestos.
AB  - Dettol (4.8% chloroxylenol, 9% pine oil and 12% isopropyl alcohol) has previously
      been reported to cause delayed upper airway obstruction when ingested, despite
      the product being labelled as non-poisonous. Domestos (1-5% sodium hypochlorite)
      is used as a household and toilet cleaner. This paper reports a rare case in
      which both agents were consumed together in significant quantities, and caused
      stridor and impending airway obstruction requiring endotracheal intubation in the
      emergency department. Patients who have ingested this combination of cleaning
      agents are at high risk of acute airway compromise, and should have expert upper
      airway evaluation and control as soon as possible after admission.

PMID- 15167196
TI  - Diagnosis in an acute organophosphate poisoning: report of three interesting
      cases and review of the literature.
AB  - Organophosphates may cause serious life-threatening conditions, such as an
      initial acute cholinergic crisis and intermediate syndrome. Each of these
      conditions has a potential for respiratory failure requiring ventilatory support.
      For this reason, it is very important to recognize them early, especially to
      institute appropriate management. The diagnosis of organophosphate poisoning is
      based essentially on a clinical assessment, followed by laboratory examinations.
      Sometimes the diagnosis may be difficult, as in case 1, identified initially as
      brainstem stroke. However, if neurological syndromes associated with
      organophosphate poisoning are well known, they can easily be distinguished from
      other conditions that resemble them. Two cases displayed the symptoms and signs
      of intermediate syndrome; however, one case (no. 2) did not have severe poisoning
      on admission but needed artificial ventilation. Each case recovered completely
      from organophosphate poisoning as a result of early diagnosis and appropriate
      therapy. Therefore, we would like to describe the clinical and laboratory
      features of these syndromes, observed in three interesting cases, and to
      emphasize the importance of early and accurate diagnosis for the appropriate
      management of acute organophosphate poisoning.

PMID- 15167197
TI  - An unusual case of syncope.
AB  - We describe the case of a woman, who had previously undergone tubal
      sterilization, and later experienced two episodes of orthostatic hypotension
      during menstruation, as a result of an ectopic pregnancy.

PMID- 15167198
TI  - Preventive treatment for re-expansion pulmonary oedema.

PMID- 15167200
TI  - The obesity epidemic, metabolic syndrome and future prevention strategies.
AB  - The epidemic of obesity and overweight poses a major challenge to the prevention
      of chronic noncommunicable diseases throughout the world. In some developing
      countries it presents a double burden alongside enduring problems of
      undernutrition. Current IOTF estimates suggest that at least 1.1 billion adults
      are overweight including 312 million who are obese. The prevalence of obesity has
      doubled or even risen threefold in less than two decades, while in children this
      is rising at an even faster rate in some regions of Europe to levels of up to 36%
      in parts of Italy and elsewhere. The comparative burden of disease due to raised
      body mass index is among the top five leading risk factors in both developed and
      low mortality developing countries. When viewed in conjunction with the burden of
      raised cholesterol and hypertension, these components of the metabolic syndrome
      form the major cause of mortality and disease in Europe and are guaranteed to
      increase with the rising trend in overweight and obesity while amplifying the
      burden of cardiovascular disease. The increase in childhood obesity will,
      unchecked, accentuate the rise in early adult type 2 diabetes and cardiovascular
      disease. CONCLUSIONS: A fundamental policy shift is required to widen
      responsibility for the prevention of diet, activity and weight-related ill health
      across the whole of Europe's population. Only such a comprehensive approach
      offers any realistic prospect of averting a public health catastrophe for Europe
      and indeed for the whole world.

PMID- 15167201
TI  - Collaborative meta-analysis of prospective studies of plasma fibrinogen and
      cardiovascular disease.
AB  - BACKGROUND: Many long-term studies have reported on associations of plasma
      fibrinogen concentration with cardiovascular disease, but few have been large
      enough to provide reliable estimates in different circumstances. Moreover, most
      published prospective studies have related disease risk only to baseline values
      of plasma fibrinogen (which can lead to substantial underestimation of any risk
      relationships) and have corrected only for baseline values of possible
      confounding factors (which can lead to residual biases). OBJECTIVES: By
      appropriate combination of data from individual participants from all relevant
      prospective studies in a systematic 'meta-analysis', with correction for
      regression dilution, the Fibrinogen Studies Collaboration will aim to
      characterize more precisely than has previously been possible the strength and
      shape of the age- and sex-specific associations of plasma fibrinogen with
      coronary heart disease (and, where data are sufficient, with other vascular
      diseases). It will also help to determine to what extent such associations are
      independent of possible confounding factors. METHODS: A central database has been
      established containing data on plasma fibrinogen, sex and other potential
      confounding factors, age at baseline fibrinogen measurement, age at event or at
      last follow-up, major vascular morbidity and cause-specific mortality.
      Information about any repeat measurements of fibrinogen and potential confounding
      factors is being sought to allow study-specific correction for regression
      dilution. The analyses will involve age-specific regression models. Synthesis of
      the available prospective studies of plasma fibrinogen will yield information on
      more than 10000 incident cardiovascular deaths and events among the approximately
      200000 total participants who have been monitored, on average, for about 10
      years.

PMID- 15167202
TI  - The Swedish National Programme for Quality Control of Secondary Prevention of
      Coronary Artery Disease--results after one year.
AB  - BACKGROUND: Guidelines for the prevention of coronary artery disease (CAD) have
      been developed both in Europe and in the USA. However, several surveys have shown
      that these guidelines are poorly implemented in clinical practice.
      DESIGN/METHODS: The Swedish Quality Control Programme on Secondary Prevention of
      CAD includes patients after myocardial infarction, or having undergone coronary
      artery surgery or percutaneous coronary intervention. Fifty of Sweden's 79
      hospital districts are currently participating. Patients are asked to send report
      cards regarding risk factor management to a central registry after discharge from
      hospital, at a 3-6 month visit and then yearly for 5 years. RESULTS: Results
      based on data from 1 year after the index event show that a majority of patients
      reach targets for serum cholesterol (70%), and low-density lipoprotein (LDL)
      cholesterol (71%). Mean value for total cholesterol is 4.6 (+/-SD 0.9) mmol/l,
      LDL-cholesterol 2.7 (+/-SD 0.8) mmol/l. Blood pressure targets are less often
      achieved, with 58% reaching the European Society of Cardiology target for
      systolic (<140 mmHg) and 81% for diastolic (<90 mmHg) blood pressure. A large
      proportion of patients are prescribed preventive drugs: aspirin (96%), beta
      blockers (78%) and lipid-lowering drugs (83%). CONCLUSIONS: The Swedish Quality
      Control Programme is one of the first attempts to assess implementation of
      guidelines on a national level based on patient participation. It is hoped that
      shared care programmes and increased patient involvement with feedback on
      achieved treatment goals in relation to guidelines will improve outcomes in
      patients with CAD.

PMID- 15167203
TI  - Prognostic significance of ventricular arrhythmia modified by ability to adapt to
      stressful situations.
AB  - BACKGROUND: Ventricular arrhythmia is a risk factor for myocardial infarction and
      mortality but many individuals with this abnormality live long and healthy lives.
      The aim of this study is to analyse the prognostic significance of frequent and
      complex ventricular arrhythmia in men who differed regarding ability to adapt to
      a stressful situation. DESIGN: Prospective cohort study. METHODS: The serial
      Color Word Test is a semi-experimental way to assess how individuals behave in a
      stressful encounter. This test was included in the prospective cohort study 'Men
      born in 1914' together with 24-h ambulatory electrocardiographic recordings at a
      baseline examination in 1982/83. Behaviour in the test was categorized as either
      adaptive or maladaptive. Behaviour in the test and occurrence of ventricular
      arrhythmia at baseline were analyzed in relation to incidence of myocardial
      infarction and mortality during approximately 14 years of follow-up. RESULTS:
      Multivariate analyses showed that ventricular arrhythmia was not associated with
      the incidence of myocardial infarction or all-cause mortality in the presence of
      an adaptive behaviour. Ventricular arrhythmia together with a maladaptive
      behaviour was associated with the incidence of myocardial infarction [relative
      risk (RR) 2.43; 95% confidence interval (CI) 1.37 to 4.31] and with all-cause
      mortality (RR 1.56; 95% CI 1.01 to 2.41) during follow-up. CONCLUSIONS: A
      maladaptive behaviour in a stressful encounter makes men with
      electrocardiographically detected ventricular arrhythmias more vulnerable and
      thereby exposed to an increased risk of a future myocardial infarction and
      overall mortality.

PMID- 15167204
TI  - Interactions between fibrinolysis, lipoproteins and leptin related to a first
      myocardial infarction.
AB  - BACKGROUND: The summarized importance of haemostatic and metabolic variables
      (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting
      first myocardial infarction, as well as possible interactions among these
      variables, have not been reported. DESIGN: A prospective case-control study
      nested within the Northern Sweden Health and Disease Cohort. METHODS: Sixty-two
      men diagnosed with a first myocardial infarction were sex- and age-matched with
      124 controls. Conditional logistic regression was conducted including established
      risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue
      plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin,
      proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin.
      Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and
      proinsulin. RESULTS: Smoking, low plasma levels of apo A-I and high plasma levels
      of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with
      myocardial infarction in univariate conditional logistic regression analysis.
      High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI), 2.04-222] and
      Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93)
      remained significant risk determinants in multivariate analysis with smoking
      habits, body mass index, hypertension, cholesterol, and diabetes included as
      covariates. There were non-significant synergic interactions between high Lp(a)
      and leptin and tPA, respectively, and between high Lp(a) and low apo A-I.
      CONCLUSION: Plasma levels of tPA, Lp(a), and apo A-I are independently associated
      with subsequent development of a first myocardial infarction in men.

PMID- 15167205
TI  - Determinants of maximal exercise performance in chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is characterized by symptoms like
      fatigue, dyspnoea and limited exercise performance. It has been postulated that
      maximal exercise performance (Wmax) is predominantly limited by skeletal muscle
      function and less by heart function. AIM: To study the interrelation between most
      relevant muscle and anthropometrical variables and Wmax in CHF patients in order
      to develop a model that describes the impact of these variables for maximal
      exercise performance. DESIGN: In 77 patients with CHF Wmax was assessed by
      incremental cycle ergometry until exhaustion (20 Watt/3 min). Peak torque
      (strength) and total work (endurance) for the quadriceps and hamstrings were
      assessed by isokinetic dynamometry. Isometric strength was measured by hand
      dynamometry. Relevant muscle areas were calculated by computerized tomography
      scan. RESULTS: Significant correlations between Wmax and isokinetic muscle
      parameters (peak torque and total work) ranged from 0.41-0.65 (P<0.01). Other
      significant relationships (P<0.01) with Wmax were obtained for age (r=-0.22),
      gender (r=0.45), fat free mass (FFM) (r=0.51), quadriceps muscle area (r=0.73),
      hamstrings muscle area (r=0.50), upper leg muscle function (i.e., a combination
      of muscle strength and muscle endurance) (r=0.71) and isometric strength
      (r=0.63). Multiple regression analysis showed that upper leg muscle function and
      quadriceps muscle area could predict 57% of the variance in Wmax. CONCLUSION:
      Muscle strength and muscle endurance, combined with quadriceps muscle area are
      the main predictors of maximal exercise performance in patients with CHF.

PMID- 15167206
TI  - Changes in alcohol intake and risk of coronary heart disease and all-cause
      mortality in the MONICA/KORA-Augsburg cohort 1987-97.
AB  - BACKGROUND: : Most studies on the effect of alcohol consumption on coronary heart
      disease or all-cause mortality assess alcohol intake at one point in time and
      therefore do not take into consideration changes in drinking habits over time. We
      investigate whether a second assessment of alcohol intake substantially improves
      estimation of the effects of alcohol intake on these outcomes. DESIGN: : A
      prospective cohort study of 2710 men and women, age 35-64 years at baseline in
      1984/85 in the Augsburg region in southern Germany. We recorded incident fatal
      and non-fatal coronary events and all-cause mortality until 1997. Alcohol intake
      and other explanatory variables were assessed in 1984/85 and 1987/88. METHODS: :
      Based on these assessments, participants were classified as non-drinkers,
      quitters, starters and constant drinkers. We calculated hazard rate ratios for
      coronary events and all-cause mortality in these groups and adjusted for several
      potential confounders using Cox's proportional hazards model. These estimates
      were compared with hazard rate ratios based on a single assessment of alcohol
      intake in 1987/88. RESULTS: : Among male constant drinkers the adjusted hazard
      rate ratio (HRR) for coronary events was lowest among those consuming 0.1-19.9 g
      alcohol per day, compared with non-drinkers [HRR 0.29; 95% confidence interval
      (CI) 0.12-0.70]. The lowest all-cause mortality risk was observed among men
      drinking 20.0-39.9 g per day (HRR 0.48; 95% CI 0.26-0.88). In female constant
      drinkers the HRR for all-cause mortality was 0.71 (95% CI 0.40-1.26) for those
      reporting 0.1-19.9 g daily alcohol consumption. Hazard rate ratios for alcohol
      intake classified by two assessments consistently revealed a more pronounced
      beneficial effect of alcohol consumption than those for alcohol intake groups
      based on a single measurement. CONCLUSIONS: : Assessment of alcohol intake at two
      points in time seems slightly to improve the risk estimation for coronary heart
      disease (CHD) and for all-cause mortality, compared with a single measurement.
      Thus, our findings strengthen the evidence of a beneficial effect of light to
      moderate alcohol consumption on coronary heart disease and all-cause mortality.

PMID- 15167207
TI  - Fluoride in the drinking water and the geographical variation of coronary heart
      disease in Finland.
AB  - BACKGROUND: Fluoride in drinking water prevents dental disease, which in turn has
      been reported to increase the risk of coronary heart disease (CHD). Since
      mortality from CHD in Finland is high in the north-east where the fluoride
      content of drinking water is low, the association was examined here in more
      detail. DESIGN: Mortality from CHD during the period 1961-1995 in 365 rural areas
      of Finland (188 888 deaths) was linked with 2131 drinking water fluoride
      determinations performed in 1958 using negative binomial regression, adjustments
      being made for sex, age, mean income of the resident commune and drinking water
      magnesium and calcium. RESULTS: An inverse J-shaped relationship was found
      between drinking water fluoride and CHD, the association being most pronounced in
      the 1960s and levelling off consistently as a function of time. In 1961-1970, the
      adjusted mortality from CHD was 22% (95% confidence interval 18-27%) lower in the
      fourth quintile of fluoride (0.15-0.30 mg/l) than in the first quintile (0.00
      0.06 mg/l) but this deficit reduced to 13% (7-18%) in 1991-1995. CONCLUSIONS:
      Although causality cannot be asserted, the geographical pattern of CHD in Finland
      is consistent with the concentration of fluoride in drinking water. One mechanism
      could be that fluoride prevents dental infections, which in turn reduces
      mortality from CHD. The more widespread use of fluoridated toothpastes, soft
      drinks and certain food items since the 1960s may have reduced the significance
      of drinking water as a source of fluoride.

PMID- 15167208
TI  - QT dispersion, QT maximum and risk of cardiac death in the Caerphilly Heart
      Study.
AB  - BACKGROUND: It has been postulated that increased inter-lead differences in QT
      interval (QT dispersion) and the maximum QT interval (QTmax), in the standard 12
      lead electrocardiogram (ECG), may be associated with an increased risk of cardiac
      death. The aims of this study were to assess the relationship between QT
      dispersion and QTmax, corrected and uncorrected for heart rate, and the risk of
      cardiac death. DESIGN: Nested case-control study within the Caerphilly
      prospective cohort study. METHODS: We studied 2512 men who participated in phase
      1 of the Caerphilly study between 1979 and 1983. After a mean follow up of 7.1
      years, 218 men had died from coronary heart disease and these men were compared
      with 218 age-matched controls. RESULTS: Data are presented on 422 patients with
      ECG suitable for analysis, 207 cases and 215 controls. Four trained observers
      measured the QT intervals and the reliability of each observer was estimated
      using repeat measurements on a randomly chosen sub-sample of ECGs. Median
      corrected QT dispersion and corrected QTmax were significantly higher in cases
      than in controls (51.9 versus 47.7 ms [P=0.01] and 430 versus 421 ms [P<0.001]
      respectively). In univariate analyses by quartiles of corrected QT dispersion and
      corrected QTmax, increased risk was largely confined to the upper quartile of the
      distribution with these subjects having twice the risk of those in the lower
      quartile [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.2-3.7 and 2.56
      (95% CI 1.5-4.5) respectively]. In logistic regression analysis, adjusted for
      age, smoking, body mass index, hypertension, history of myocardial infarction and
      ECG Minnesota code, we observed an increased risk in the upper quartile of the
      corrected QT dispersion relative to the other three quartiles combined [adjusted
      OR=1.74 (P=0.03)]. The magnitude of this association was increased in analyses
      based on the data from the most reliable observers. The association between
      corrected QTmax and cardiac death was attenuated in multivariate analysis. The
      findings in relation to both uncorrected QT dispersion and uncorrected QTmax were
      similar, i.e., consistent with a significant independent effect of QT dispersion
      but not QTmax for cardiac death in multivariate analysis. CONCLUSION: The data
      suggest that QT dispersion is an independent predictor of cardiac death provided
      it can be measured with sufficient reliability. The association is non-linear
      with increased risk largely confined to the upper quartile of the distribution.
      The QT maximum is not an independent predictor of cardiac death.

PMID- 15167209
TI  - Serum parathyroid hormone levels predict coronary heart disease: the Tromso
      Study.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with hypertension,
      coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate
      serum parathyroid hormone (PTH) levels as an independent risk factor for coronary
      heart disease (CHD) in subjects with serum calcium within the reference range.
      DESIGN: Population-based cross-sectional study. METHODS: The Tromso Study was
      attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570
      subjects. They all completed a questionnaire on medical history, including
      questions on angina pectoris and myocardial infarction along with a food
      frequency questionnaire. A total of 1459 men and 1753 women with serum calcium
      2.20-2.60 mmol/l, serum creatinine<121 micromol/l and who did not use diuretics
      were included in the present study. Linear regression was used to reveal
      associations between PTH, age, body mass index, serum calcium, calcium intake,
      cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status.
      A logistic regression model was used to find the independent predictors of CHD.
      RESULTS: When stratified for age the rate of CHD was higher in the subjects with
      serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels
      [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95%
      CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30
      pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for
      men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90
      pmol/l for men and <1.80 pmol/l for women). CONCLUSIONS: Serum PTH predicts CHD
      in subjects with calcium levels within the reference range. This may indicate a
      role for PTH in the development of CHD.

PMID- 15167210
TI  - Screening for psychosocial risk factors in patients with coronary heart disease
      recommendations for clinical practice.
AB  - Psychosocial risk factors like low socio-economic status, chronic family or work
      stress, social isolation, negative emotions (e.g., chronic depression or acute
      anxiety), and negative personality patterns such as Type-D-pattern or hostility,
      may contribute significantly to the development and adverse outcome of coronary
      heart disease. Therefore, systematic screening for psychosocial risk factors in
      cardiological practice is recommended in order to initiate adequate intervention
      strategies, e.g., to involve additional psychosocial counselling or treatment.
      Reliable methods to assess psychosocial risk factors are: (1) standardized,
      structured interviews; (2) standardized questionnaires, and (3) 'single-item'
      questions to be included into the cardiologists' clinical interviews. While
      structured interviews should be restricted to trained professionals,
      questionnaires are easily to administer, and have frequently been used in the
      field of cardiology. 'Single item' questions are sufficiently reliable and the
      most timesaving way to screen for psychosocial factors. For clinical practice, a
      two-step evaluation is recommended: firstly, cardiologists should include 'single
      item' questions into their routine interview and/or use questionnaires in order
      to screen for a potential problem. Secondly, if problems are indicated, patients
      should be passed to qualified professionals for structured clinical interview.
      Instruments of all three methods are briefly presented, and implications for
      further treatment are discussed.

PMID- 15167212
TI  - The Mediterranean diet and its protective role against cancer.

PMID- 15167214
TI  - Smoking, alcohol drinking and cancer risk for various sites of the larynx and
      hypopharynx. A case-control study in France.
AB  - The aim of this work was to study the effects of alcohol and tobacco consumption
      on laryngeal and hypopharyngeal cancer and to compare these across subsites
      (glottis, supraglottis, epilarynx, hypopharynx). Data from a hospital-based case
      control study including 504 male cases (105 glottic cancers, 80 supraglottic
      cancers, 97 epilaryngeal cancers and 201 hypopharyngeal cancers) and 242 male
      controls with non-respiratory cancers were used for this analysis. Information
      about sociodemographic characteristics, detailed alcohol and tobacco consumption
      was collected through face-to-face interviews. Statistical analysis used logistic
      regression, and subsites were compared with polytomous logistic regressions. The
      risk of laryngeal and hypopharyngeal cancer increased with tobacco (duration and
      amount) and alcohol consumption; the effect of both agents was multiplicative.
      From the lowest to the highest consumption level, odds ratios ranged from 1.4 to
      5.9 among regular drinkers and from 3 to 44 among current smokers. Risks among ex
      smokers were approximately one-third of those for current smokers. Slightly
      elevated odds ratios were associated with consumption of black tobacco (OR=1.2)
      and hand-rolled cigarettes (OR=1.2). The risk of cancer was not clearly
      associated with the type of alcoholic beverage. Subsites did not differ
      significantly according to tobacco smoking, but differed according to alcohol
      consumption, with a significantly higher increased risk for hypopharyngeal than
      for glottic and supraglottic cancers.

PMID- 15167213
TI  - Meat intake and the recurrence of colorectal adenomas.
AB  - A large multicenter randomized controlled trial was re-assessed to check whether
      meat intake and a reduction in its consumption are associated with recurrence of
      adenomatous polyps of the large bowel, which are precursors of most colorectal
      malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one
      or more histologically confirmed colorectal adenomas removed during a colonoscopy
      within 6 months before randomization. The subjects were followed-up for
      approximately 4 years after randomization and a colonoscopy for detecting
      adenomas was conducted at the 1st and 4th year after randomization. Dietary
      variables were assessed at baseline (T0) and in conjunction with annual visits at
      the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using
      logistic regression models for meat variables were estimated based on the average
      intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change
      (T0-T4) in intake. In the intervention group, the total reduction in median
      intake of red meat from T0 to T4 was observed by the end of 1st year itself (30
      and 31% for men and women, respectively). The analysis provide no evidence to
      suggest that lower intake or reduction in total and in red meat consumption
      during a period of 4 years reduces the risk of adenoma recurrence (including
      multiple or advanced adenoma), whereas the data suggest that high intake of fish
      is associated with lower risk of adenoma recurrence.

PMID- 15167215
TI  - Allergy and the risk of selected digestive and laryngeal neoplasms.
AB  - The relation between allergy and cancer has been investigated within an
      integrated series of case-control studies of digestive tract and laryngeal
      neoplasms conducted in Italy since the early 1990s. These included 598 patients
      with incident, histologically confirmed cancer of the oral cavity and pharynx,
      304 of the oesophagus, 1225 of the colon, 728 of the rectum, 460 of the larynx
      and 4999 controls, selected among patients admitted to the same network of
      hospitals as cases for acute, non-neoplastic diseases. Inverse associations with
      history of allergy were found for all cancer sites examined (odds ratio=0.44 for
      oral cavity and pharynx, 0.80 for oesophagus, 0.76 for colon, 0.54 for rectum and
      0.33 for larynx). The associations were consistent in strata of age and sex, and
      when subjects with a first diagnosis of allergy 5 or more years before cancer
      diagnosis or hospital admission were considered. The present study therefore
      provides further evidence for a possible protective effect of prior history of
      allergy on cancer risk.

PMID- 15167216
TI  - HER2 polymorphism and breast cancer risk in Portugal.
AB  - Breast cancer is a major public health problem around the world, and its
      carcinogenesis is not yet well understood. The human epidermal growth factor
      Receptor 2 (HER2) seems to play an important role in the development of this
      neoplasia, and genetic alterations in this gene, such as point mutations and
      polymorphisms have been detected in breast cancer patients. We analysed the
      frequency of a single nucleotide polymorphism in the HER2 gene in blood samples
      from 152 breast cancer patients and 146 healthy controls using the polymerase
      chain reaction methodology, followed by restriction fragment length polymorphism
      (PCR-RFLP). We found a twofold increase in risk of breast cancer in women who are
      carriers of a Val allele genotype-Ile/Val and Val/Val genotypes [odds ratio
      (OR)=2.00; 95% confidence interval (CI) 1.23-3.25; P=0.005]. Our results indicate
      an association between the presence of the Val allele in the HER2 polymorphism
      and the risk of breast cancer. Further studies are needed to evaluate the role of
      this polymorphism in the behaviour of breast cancer.

PMID- 15167217
TI  - Contribution of three components to individual cancer risk predicting breast
      cancer risk in Italy.
AB  - We used data from a multicentre case-control study conducted in Italy between
      1991 and 1994 on over 2500 cases of breast cancer and a comparable number of
      controls, and estimates of breast cancer incidence in Italy to compute individual
      breast cancer risk for Italian women. The estimated probabilities between age 50
      and 80 ranged from approximately 5% (for a woman with no family history and low
      modifiable risk profile) to about 30% (for a woman with young family history and
      high modifiable risk) on the basis of various women's baseline characteristics.
      Expected numbers of breast cancer cases using the present model were compared
      with those based on the USA Gail model, and with the observed ones in the
      comparison group of the Italian Tamoxifen Trial. These show a closer agreement
      between the observed and the expected total numbers of breast cancers than the
      USA Gail model. Thus, the Gail model can be improved for use in other populations
      by using estimates of incidence and risk which are more appropriate to the target
      population.

PMID- 15167218
TI  - Childhood obesity and hormonal abnormalities associated with cancer risk.
AB  - There is growing evidence that overweight and obesity increase the risk of
      certain cancers. Studies in adults support the role of insulin-like growth
      factors (IGFs) and oestrogens in the pathogeneses of several cancers. We propose
      that hormone alterations described as risk factors for cancer in obese adults are
      present in prepubertal obese children. A group of obese children aged 6-9 years
      (n=40), and control group paired for age and sex, were used for the study. The
      obese children presented a significantly high level of IGF-I (P=0.0173) and
      insulin (P=0.0250), with a drop in sex hormone-binding globulin (SHBG)
      (P=0.0282). The 17 beta-oestradiol (E2)/SHBG ratio increase in obese subjects was
      marginally significant (P=0.0635). Grouping together all the children in
      quartiles for insulin and body mass index, the upper quartiles showed a rise in
      IGF-I and E2/SHBG. In a multivariant correlation analysis, only height (partial
      r=0.2464) and insulin (partial r=0.3002) were independent prediction variables
      for IGF-I concentration. The only variables statistically correlated with the
      E2/SHBG ratio were insulin (r=0.2879) and IGF-I (r=0.4140). The obese children in
      our study showed hormone changes described as risk factors for cancer in obese
      adults. These changes were significantly associated with the hyperinsulinaemia.
      We hypothesize that this potential risk should be taken into account given the
      long period of exposure involved in the presence of hormone alterations at such
      early ages.

PMID- 15167219
TI  - University and medical education and the risk of cancer in Sweden.
AB  - Socio-economic gradients are known to exist in cancer but we want to focus on the
      university-educated population and specifically on physicians to find out whether
      their special educational background on cancer causation helps them to avoid
      cancers. The analysis was based on the latest update of the Swedish Family-Cancer
      Database, in which the educational level was obtained from the national census of
      1970 for those aged 30 years or older and the follow-up for cancer was extended
      up to year 2000. We determined standardized incidence ratios (SIRs), adjusted for
      several variables, for cancer among men and women in four educated groups and
      compared them with those with less than 9 years of education. Total cancer risks
      did not differ much, but at individual sites, the university-educated population
      showed consistent, increasing or decreasing trends. The educated group showed
      high SIRs for melanoma and skin cancer and for female breast cancer. At all these
      sites, SIRs for in situ tumours exceeded those for invasive tumours; the highest
      SIR was 4.81 for male MD, PhDs for in situ melanoma. SIR for in situ breast
      cancer for female physicians was 1.95. SIR for non-Hodgkin's lymphoma for male
      MD, PhDs was 2.20 but their risk of stomach cancer was only 0.26. Tobacco-related
      cancers were decreased among the educated group. Cancer risks for physicians were
      not different from those of their academic colleagues. Some of the increased
      risks were probably due to lead-time bias, caused by early diagnosis.

PMID- 15167220
TI  - Price and consumption of tobacco in Spain over the period 1965-2000.
AB  - Changes in cigarette price have had an appreciable impact on smoking prevalence
      in several countries. We analysed the price elasticity of demand for cigarettes
      (effect of price of cigarettes on tobacco consumption) between 1965 and 2000 in
      Spain. For total consumption of cigarettes, a 1% increase in price is associated
      with a 0.19% decrease of consumption (price elasticity of -0.19; P<0.01). The
      real price of blond cigarettes was significantly and inversely associated with
      blond cigarette consumption: on average, smoking prevalence decreased 1.25% for a
      1% increase in the real price of cigarettes (significant price elasticity of 
      1.25). For black cigarettes we found a lower but still high and significant
      elasticity of -0.61. There is an inverse relation between price and consumption
      of cigarettes in Spain, indicating that interventions at the economic level (such
      as real increases in prices) may have an important public health impact in
      tobacco control.

PMID- 15167221
TI  - Incidence of anal carcinoma in Vaud, Switzerland, 1979-2001.
AB  - Substantial rises in anal cancer incidence have been registered over the last few
      decades in the USA and a few Nordic countries. Incidence trends in the Swiss
      population of Vaud (about 602,000 inhabitants) over the period 1979-2001 were
      considered. Rates were around 0.3-0.5 per 100,000 men (age-standardized, world
      population) and 1.1-1.4 per 100,000 women, in the absence of any consistent trend
      over time. The epidemiology of anal cancer appears therefore different in this
      Swiss population as compared with North America and northern Europe.

PMID- 15167223
TI  - The traditional diet of Greece and cancer.
AB  - The term 'Mediterranean diet', implying that all Mediterranean people have the
      same diet, is a misnomer. The countries around the Mediterranean basin have
      different diets, religions and cultures. Their diets differ in the amount of
      total fat, olive oil, type of meat, wine, milk, cheese, fruits and vegetables;
      and the rates of coronary heart disease and cancer, with the lower death rates
      and longer life expectancy occurring in Greece. The diet of Crete represents the
      traditional diet of Greece prior to 1960. Analyses of the dietary pattern of the
      diet of Crete shows a number of protective substances, such as selenium,
      glutathione, a balanced ratio of n-6/n-3 essential fatty acids (EFA), high
      amounts of fibre, antioxidants (especially resveratrol from wine and polyphenols
      from olive oil), vitamins E and C, some of which have been shown to be associated
      with lower risk of cancer, including cancer of the breast. Epidemiological
      studies and animal experiments indicate that n-3 fatty acids exert protective
      effects against some common cancers, especially cancers of the breast, colon and
      prostate. Many mechanisms are involved, including suppression of neoplastic
      transformation, cell growth inhibition, and enhanced apoptosis and anti
      angiogenicity, through the inhibition of eicosanoid production from n-6 fatty
      acids; and suppression of cyclooxygenase 2 (COX-2), interleukin 1 (IL-1) and IL-6
      gene expression by n-3 fatty acids. Recent intervention studies in breast cancer
      patients indicate that n-3 fatty acids, and docosahexaenoic acid (DHA) in
      particular, increase the response to chemopreventive agents. In patients with
      colorectal cancer, eicosapentaenoic acid (EPA) and DHA decrease cell
      proliferation, and modulate favourably the balance between colonic cell
      proliferation and apoptosis. These findings should serve as a strong incentive
      for the initiation of intervention trials that will test the effect of specific
      dietary patterns in the prevention and management of patients with cancer.

PMID- 15167224
TI  - A new theory of tumours and tumorigenesis.

PMID- 15167225
TI  - Emotions in plants.

PMID- 15167226
TI  - Regulations, control of clinical judgment, medical errors, and medical conduct to
      avoid mishaps.

PMID- 15167227
TI  - A case study of amnion rupture sequence with acalvaria, blindness, and clefting:
      clinical and psychological profiles.
AB  - The purpose of this article is to report the case of a 10-year-old girl born with
      anophthalmia, bilateral oblique facial clefts, and missing scalp and bones over
      the temporal and parietal areas of the cranial vault bilaterally. Early amnion
      rupture seems to be the most probable cause of this rare combination of
      anomalies. Because no similar case has been reported in the literature so far, we
      describe here the clinical and psychosocial history of this unusual patient, who
      has been able to live the intellectually and socially normal life of a blind
      child in spite of the major craniofacial deformities. The already completed and
      possible future therapeutic strategies are discussed.

PMID- 15167228
TI  - Unicoronal suture immobilization in the fetal rabbit.
AB  - Pre-clinical evaluation of surgical procedures aimed to correct craniosynostosis
      is ideally performed in species of small animals characterized by perinatal brain
      development, early skeletal maturation, and genuine synostosis in all newborns.
      It would be nearly impossible to breed such a colony to homozygosity, so most
      researchers have resorted to artificial postnatal suture immobilization. Our aim
      was to test the hypothesis that artificial immobilization of a unicoronal suture
      in the fetal rabbit (25 days of gestation) would result in neurocranial growth
      alterations similar to those seen in the 9-day postnatally immobilized or
      congenital synostotic rabbit models. The advantages of prenatal immobilization
      are that rabbits can undergo the tested corrective procedure at postnatal day 9.
      This age corresponds to a human age of 6 months and allows the deformity and the
      effects of its correction to be more readily detected. The heads of 25-day-old
      fetuses of five time-dated pregnant New Zealand white rabbits were exposed by
      hysterotomy. The left unicoronal suture of 4 fetuses in each litter was
      immobilized with a polyglactin suture piercing the frontal and parietal bone
      plates. The remaining two fetuses were sham-operated. Nine days after spontaneous
      delivery, all rabbits were marked with four titanium screws close to the sagittal
      and coronal sutures. Growth was recorded with dorsoventral cephalograms at 9 and
      90 days. The group with the immobilized suture showed a small increase in growth
      across the sagittal sutures. However, the decreases in growth at the unicoronal
      suture in both the immobilized (5.41-mm difference with sham-treated group) and
      nonimmobilized (1.17-mm difference with sham-treated group) were significant.
      Fetal immobilization results in growth alterations similar to those observed
      after postnatal immobilization.

PMID- 15167229
TI  - A report of behavioral data on three groups of patients with craniofacial
      disorders.
AB  - Longitudinal follow-up data on development and school placement are presented for
      three groups of patients. Having had or not having had early surgical
      intervention and stimulation distinguishes the two groups of patients with
      craniosynostosis. The third group is patients with cleft lip and palate who
      received early intervention but did not achieve minimal criteria for
      communication by age 22 months. Educational placement (for patients 8 to 20 years
      of age) follows the pattern of distribution of students nationally for patients
      who had early intervention.

PMID- 15167230
TI  - Zygomaticotemporal nerve passage in the orbit and temporal area.
AB  - Injury of the zygomaticotemporal nerve causes paresthesia in its distributed
      area, and its entrapment induces protractive pain in case of manipulation of the
      orbital lateral wall, a Gillies or Dingman reduction procedure for a zygomatic
      fracture, or an endoscopic subperiosteal facelift. The aim of this study was to
      elucidate the surgical anatomy of the zygomaticotemporal nerve in the orbit and
      temporal area. Twenty hemifaces from 10 adult Korean cadavers (10 male and 10
      female) were used in the study. The zygomaticotemporal nerve ran along the
      lateral wall of the orbit, passed through the zygomaticotemporal foramen, and
      reached to the temporal fossa. The point where the zygomaticotemporal nerve
      appears at the margin of zygomatic bone is defined as the vulnerable point (Vp);
      hence, the nerve might be injured during surgical procedures. The Vp was 11.29 +/
      2.65 mm below the zygomaticofrontal suture and 21.76 +/- 2.76 mm from the
      superior border of zygomatic arch. The most vulnerable points were within a 10-mm
      diameter circle (vulnerable zone). Its center was 11 mm from the
      zygomaticofrontal suture at an angle of 45 degrees inferolaterally. The
      zygomaticotemporal nerve ran between the deep layer and the superficial layer of
      the deep temporal fascia. It ran just superficial to the deep layer of the deep
      temporal fascia toward the temporal area and innervated the temporal skin. The
      area innervated by terminal branches of the zygomaticotemporal nerve included a
      circle with 30-mm diameter, with the center located 10 mm superior to the top of
      the auriculocephalic sulcus and 30 mm lateral to the lateral canthus. Precautions
      should be taken when working in the area of the vulnerable zone during the
      Dingman procedure involving periorbital incision in case of zygomatic fracture.

PMID- 15167231
TI  - Cemento-ossifying fibroma of the ethmoidal sinus in a child presenting with
      isolated pain in the nasal region.
AB  - The authors present a case of a previously healthy 8-year-old girl who presented
      with pain on the right side of the nose (bony part) radiating to the frontal and
      temporal regions. Physical examination was normal, whereas magnetic resonance
      imaging (MRI) of the facial region revealed a tumor limited to the right
      ethmoidal sinus with a small extension to the medial wall and the upper part of
      the nasal septum. The tumor was removed by using a 5-degree nasoscope and sent
      for pathologic examination, which revealed a cemento-ossifying fibroma of the
      ethmoidal sinus. This is a rare condition, and MRI is a valuable tool in its
      detection because results of physical examination may be normal in patients
      reporting nasal pain. According to the World Health Organization classification,
      this tumor is a variant of cementifying fibromas, which represent a subgroup of
      cementomas, fibro-osseous lesions containing cementum. Cementifying fibromas are
      rare tumors. They are usually small, asymptomatic lesions, but although benign,
      they can develop into aggressive, expansible masses.

PMID- 15167232
TI  - Surgical correction of craniosynostosis in malignant osteopetrosis.
AB  - In osteopetrosis, bone healing is complicated by progressive sclerosis. A 2-year
      old blind boy with malignant osteopetrosis developed increased intracranial
      pressure secondary to craniosynostosis. Osteopetrosis had already been treated
      with bone marrow transplantation (BMT), and bone remodeling seemed to be
      restored. A craniotomy was performed. The postoperative course and bone healing
      were uneventful. After successful BMT, craniofacial procedures seem to be
      possible without a high risk for osteomyelitis.

PMID- 15167234
TI  - A rare location of benign osteoblastoma: review of the literature and report of a
      case.
AB  - Benign osteoblastoma is a rare primary bone tumor that constitutes approximately
      1% of all primary bone tumors. Its occurrence in the craniomaxillofacial region
      as also rare and represents only 15% of all osteoblastomas. The tumor shows a
      predilection for the male gender and constitutes less than 1% of all tumors of
      the maxillofacial region. In the maxillofacial region, the mandible is affected
      more frequently than the maxilla, and the coronoid process of the mandible is the
      area most rarely affected by osteoblastoma. Before this report, 53 cases have
      been reported in the literature. In this report, a rare location of
      osteoblastoma, namely, the coronoid process of the mandible, is described.

PMID- 15167235
TI  - Unusual penetrating cranio-orbital injury by a cut-off wheel.
AB  - The rare case of a penetrating cranio-orbital injury and the surgical treatment
      is presented. A 38-year-old woman was brought to the Emergency Unit of the
      University of Leipzig Hospital after suffering a severe craniocerebral injury
      from a broken cut-off wheel. A computed tomography (CT) scan demonstrated the
      entrance of the cut-off wheel with extension from the left sinus maxillaris and
      frontalis through the median part of the left-sided orbit to the anterior skull
      base. After removing the cut-off wheel and metal splinters, the neurosurgeon
      performed an osteoplastic bifrontobasal trepanation with revision of the wound
      channel. Three years later, the patient has no neurological deficit and the CT
      scan shows a small hypodensity behind the sinus frontalis on the left side.

PMID- 15167236
TI  - An unusual traumatic fracture of the mandibular symphysis resembling horizontal
      osteotomy for genioplasty.
AB  - The authors report a rare case of mandibular fracture caused by a flying object,
      discuss the mechanism of the fracture, and review the literature. The patient was
      a 40-year-old male soldier in the Self Defense Force (SDF). During a mock battle
      of the SDF Agency, a shell splinter penetrated his mentum and caused a fracture
      of the mandibular symphysis that resembled horizontal osteotomy for genioplasty.
      A horizontal fracture of the mandibular symphysis is very rare, and on clinical
      inspection, the authors found the general course of the clinical fracture line
      coincided with the weakest portion of the mandible. A powerful blast can cause an
      object to become airborne and injure persons in the vicinity, as did the metallic
      fragments that caused the mandibular fracture in patient reported here. Thus,
      when examining victims of such traumas, the possibility that a foreign object
      might have penetrated the body should be kept in mind. A thorough inspection of
      injuries resulting from explosions is mandatory.

PMID- 15167240
TI  - The fate of hydroxyapatite cement used for cranial contouring: histological
      evaluation of a case.
AB  - Craniofacial contouring is a commonly performed procedure applied for traumatic
      and postsurgical cranial vault or facial skeleton irregularities. Hydroxyapatite
      cement is an alloplastic material composed of tetracalcium phospate and dicalcium
      phospate anhydrous that transforms into a paste-like substance when these two
      compounds placed in an aqueous environment. This mixture, which is a nonceramic
      microporous calcium phosphate combination, is another alternative for refining
      the craniofacial contour. There are not enough data regarding bone formation
      within this material after its use in human beings, however. A case requiring
      secondary craniofacial contouring after a motor vehicle accident is presented.
      Hydroxyapatite cement was used for reconstruction, and a second look was carried
      out for further correction during which secondary contouring of the cement was
      made and a sample of the previously implanted material was histologically
      evaluated. It was observed in this case that hydroxyapatite cement is
      incorporated within the surrounding bony structures and permits secondary
      contouring procedures. New bone and vessel formation was also detected within the
      implanted material, but this was limited and thus was not convincing for
      significant osteoconversion as seen in animal studies.

PMID- 15167238
TI  - Crouzon syndrome: phenotypic signs and symptoms of the postnatally expressed
      subtype.
AB  - In a retrospective study, the characteristics of a group of patients (n = 9) with
      a postnatally expressed Crouzon syndrome were described. Although they do not
      always display the physical signs of craniosynostosis, such patients are highly
      at risk of developing symptoms secondary to multiple suture synostosis. By
      reviewing the hospital files, radiographs, and three-dimensional computed
      tomography scans of these patients, it was possible to describe the pattern of
      suture obliteration chronologically. Furthermore, certain phenotypic signs and
      symptoms such as skull shape and development of digital impressions, a bulge at
      the bregma, and intracranial hypertension were inventoried as well as patients'
      genotypes. Interestingly, ossification started at the lambdoid sutures in at
      least four patients and most likely in three additional ones. The coronal sutures
      were the last to ossify in at least three of the patients. Various skull shapes
      were encountered. Furthermore, all nine patients developed digital impressions,
      starting occipitally in eight of them. Seven patients developed a bulge at the
      bregma, and four of them exhibited intracranial hypertension. The genotype varied
      in our patients. To recognize patients with postnatal Crouzon syndrome as soon as
      possible, special attention must be paid to 1) occipital development of digital
      impressions and/or ossification of sutures, 2) development of a prominent bregma,
      3) development of intracranial hypertension, and/or 4) progressive characteristic
      "crouzonoid" features. Such patients can be considered as representing a subtype
      of Crouzon syndrome. To prevent or treat intracranial hypertension and/or loss of
      vision, surgical intervention should be performed at the onset of progressive
      craniosynostosis between 1 and 2 years of age.

PMID- 15167242
TI  - Pressure-flow measurements for selected oral sound segments produced by normal
      children and adolescents: a basis for clinical testing.
AB  - Despite advances in surgery, a significant number of patients who undergo cleft
      palate repair have residual velopharyngeal insufficiency. Maxillary advancement
      may also result in velopharyngeal openings during speech. Instrumental approaches
      providing objective measures of palatal function assisting in the accurate
      diagnosis of these patients include pressure-flow measurements of velopharyngeal
      valving during speech. There is little information to guide clinicians in
      interpreting pressure-flow data when testing pediatric patients, however. The
      primary purpose of this study was to develop a method for categorizing pressure
      flow data used in the diagnosis of children and adolescents with suspected
      velopharyngeal insufficiency. This prospective study involved 56 male and female
      subjects 5 to 18 years of age. Subjects had normal speech and resonance at the
      time of testing, no history of speech therapy, no upper respiratory infections or
      allergies at the time of testing, and no orofacial anomalies. Subjects repeated
      oral syllables and the word "hamper" after an examiner. Mean pressures, airflows,
      and velopharyngeal orifice areas were obtained for each utterance produced by
      each subject. A discriminate function analysis was performed to determine whether
      data could be grouped by age, gender, or utterance type. Results indicated
      significant differences in data for age groups 5 to 8 years, 9 to 13 years, and
      14 to 18 years. There were no significant differences between data for male
      subjects versus female subjects or for different utterance types. Pressures
      generally decreased, whereas airflows and orifice areas increased with age.
      Results for 14 to 18 year olds were like those for adults. Using these data, a
      categorization scheme for velopharyngeal function was proposed for use in
      clinical testing.

PMID- 15167244
TI  - Primary post-traumatic mandibular reconstruction in infancy: a 10-year follow-up.
AB  - Ballistic trauma to the craniofacial skeleton combines the challenges of complex
      bone injury and loss with severe soft tissue injury and violation of the naso
      orbital or oropharyngeal cavities. The authors report a patient who experienced a
      unique ballistic injury at 28 months of age that resulted in loss of the
      mandibular ramus and condyle. A segmental injury to the facial nerve was also
      identified. Primary costochondral grafting and delayed interpositional nerve
      grafting was undertaken. After 10 years, the patient has nearly 40 mm of opening,
      with only slight deviation to the injured side. Her facial nerve regeneration
      provides complete orbicularis oculi function, oral competence, and only slight
      facial asymmetry. This traumatic reconstruction differs from that of patients
      with hemifacial microsomia or post-traumatic/arthritic ankylosis in that the
      joint space itself was spared. Thus, the costochondral graft benefits from the
      remaining articular disk and upper disk space and is able to rotate and
      translate. Function and growth are adequately re-established, even in this young
      pediatric patient.

PMID- 15167246
TI  - Fibrous dysplasia of the sphenoid sinus and skull base presents in an adult with
      localized temporal headache.
AB  - Fibrous dysplasia (FD) of the sphenoidal sinus is a rare disease, especially
      during adulthood. We report a case of FD of the right sphenoidal sinus in an
      adult male patient who presented with nonspecific symptoms limited to headache
      localized to the right temporal area and to the inferior orbital rim of both
      sides. Magnetic resonance imaging revealed a dense mass that occupied the entire
      right sphenoidal sinus and skull base with typical ground-glass opacification and
      bony sclerosis of the whole sphenoidal wall. The diagnosis of FD was confirmed on
      pathological examination of a biopsy taken through sphenotomy. The patient
      underwent a subcranial craniotomy for tumor resection. After more than 4 years of
      follow-up, the patient was disease-free. On the basis of these clinical features,
      it is important to consider sphenoidal FD in both young and adult patients
      complaining of an unexplained headache, because it may present unusually with
      headache localized to the temporal region or the inferior orbital rim.

PMID- 15167248
TI  - Dermatography as an adjunctive treatment of uni- and bilateral scars in
      combination with pseudo-hair formation after craniosurgery.
AB  - This article describes the use of dermatography as a method to reduce large
      cosmetically unacceptable scars in the temporo-occipital region after
      craniosurgery. Over a period of 15 years, 17 patients were treated in two to five
      1-hour sessions without local anesthesia. The results show that dermatography is
      effective in providing a lasting cosmetically satisfactory effect, with subtle
      pseudo-hair formation and color pigments stably deposited. At the same time, the
      hypertrophic scars themselves are reduced and flattened, with their tissue made
      supple.

PMID- 15167247
TI  - Expression profiling of ameloblastic carcinoma.
AB  - Ameloblastic carcinoma (AC) is a malignant epithelial odontogenic tumor that
      histologically retains the features of ameloblastic differentiation and exhibits
      cytological features of malignancy in the primary or recurrent tumor. It may
      develop within a preexisting ameloblastoma or arise de novo or from an
      odontogenic cyst. Expression profiling by DNA microarray is a new molecular
      technology that allows the analysis of cell and tissue gene expression. By using
      DNA microarrays containing 19,200 genes, several genes whose expression was
      significantly upregulated or downregulated were identified in a case of AC. The
      differentially expressed genes cover a broad range of functional activities: 1)
      transcription, 2) signaling transduction, 3) cell cycle regulation, 4) apoptosis
      control, and 5) differentiation. The data reported are, to our knowledge, the
      first genetic portrait of an AC. No final conclusion can be drawn; however, this
      portrait will be useful in investigating the biological behavior and in
      identifying possible gene targets for cancer therapy when more cases of this rare
      tumor are reported and compared.

PMID- 15167249
TI  - The role of trauma on temporomandibular joint ankylosis and mandibular growth
      retardation: an experimental study.
AB  - The purpose of this pilot study was to analyze the role of different types of
      trauma in the formation of temporomandibular joint ankylosis. The specific aim
      was to explore the physical and histological effects of trauma on
      temporomandibular joint and mandibular growth. Fifty-five growing white male
      guinea pigs were used for the study. Initially, cadaveric studies were performed
      (n = 1) to assess the topographic anatomy of the temporomandibular joint region.
      Animals were then assigned to pilot (n = 4), experimental (n = 40), and control
      (n = 10) groups. The pilot group was used to assess the technical feasibility of
      creating various trauma types and endurance of the animals to the surgery. Four
      types of trauma were carried out in the experimental group: A) intra-articular
      hematoma (n = 10), B) mechanical damage to the articular surface (n = 10), C)
      fracture of the condyle neck (n = 10), and D) excision of the condyle head (n =
      10). Each trauma group was further divided into two subgroups. Procedures were
      performed unilaterally or bilaterally in the subgroups. In the control group, no
      procedure was performed. Subjects were examined after a 2-month follow-up period.
      The development and anatomical structure of the mandible were evaluated, and
      histopathological assessment of the temporomandibular joint was carried out in
      each group. The results revealed that hyaline cartilage of the condylar head had
      an important role in the development of the mandible and traumas targeting this
      site may cause ankylosis, growth retardation, and resultant facial malformations.
      Hence, mechanical damage to the articular surface (B1, B2) and resection of the
      condylar head (D1, D2) almost always resulted in ankylosis. Intra-articular
      hematoma alone (A1, A2) was established not be a causative factor for ankylosis
      formation, however.

PMID- 15167251
TI  - Interstitial growth of bone revisited.
AB  - The distance between two or more metallic implants placed within the same flat
      bones (mandible, nasal, frontal, hyoplastron, hypoplastron) of young pigs,
      rabbits, and turtles followed by means of serial radiographs, remained the same
      for periods as long as 546 days. Thus, it is concluded that there is no
      interstitial growth. In 1743, Duhamel demonstrated that long bones grow at their
      ends and that there is no interstitial growth. This report is unique in that it
      demonstrates by use of radiopaque implants and serial radiographs that there is
      no interstitial growth of flat bones, which grow by apposition and resorption,
      and not endochondrally, such as occurs in long bones.

PMID- 15167252
TI  - Anthropometric measurements of the facial framework in adulthood: age-related
      changes in eight age categories in 600 healthy white North Americans of European
      ancestry from 16 to 90 years of age.
AB  - The aim of this cross-sectional anthropometric study was to determine the age
      related changes in the facial framework during adulthood in healthy white North
      Americans of European ancestry (261 male subjects and 339 female subjects). Five
      measurements, four horizontal and one vertical, defining the framework were taken
      from the skin and bony surface of the face in the maturation period (16-20 years)
      and in 10-year age categories of adulthood (21-90 years). As well, the thickness
      of the soft-tissue cover between these two anatomical levels was measured. The
      categories between 21 and 40 years represented early adulthood, those between 41
      and 70 years represented middle adulthood, and those between 71 and 90 years
      represented late adulthood. The forehead width in both sexes increased
      significantly on the skin and bony surface from the maturation period to early
      adulthood. In middle adulthood, the changes were significant only sporadically.
      In late adulthood, the upper and lower jaw showed a harmonious change with age,
      mostly increasing on both the skin and bony surface. The face width proved to be
      the most stable measurement and had the thinnest soft-tissue cover. No consistent
      pattern emerged during adulthood in increases or decreases within the facial
      framework; however, an unexpected harmony was noted between the values of the
      measurements in early and late adulthood in both sexes on both the skin and bony
      surface. The thickness of the soft-tissue cover at the bony landmarks was
      greatest in the midface, with a moderately decreasing tendency in both sexes. In
      the lower jaw, the soft tissue showed significant increases in thickness in early
      adulthood and moderate to large decreases in late adulthood. Anthropometric
      analysis of the facial framework in adulthood marks only the first step in
      establishing the morphological changes of the aging face. Quantitative evaluation
      of changes within the facial framework of the aging population must be carried
      out in more detail. Increased worldwide migration results in a mixing of people
      of various racial/ethnic origins and necessitates a general anthropometric
      analysis of the aging face to provide more reliable guidelines for therapy.

PMID- 15167253
TI  - The bone regenerative effect of chitosan microsphere-encapsulated growth hormone
      on bony consolidation in mandibular distraction osteogenesis in a dog model.
AB  - The purpose of this project was to study the effect of chitosan microsphere
      encapsulated human growth hormone, which causes sustained release of chitosan and
      human growth hormone after implantation on early bony consolidation in
      distraction osteogenesis of a canine model. Forty-eight dogs were used for this
      study. An external distraction device was applied to the mandibular body after a
      vertical osteotomy, and the mandibular distraction was started 5 days after the
      operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group
      was divided into a control group (I), hyaluronic acid group (II), chitosan
      microsphere group (III), and chitosan microsphere-encapsulated human growth
      hormone group (IV). Normal saline was injected in group I. In group II, a 1-ml
      volume of hyaluronic acid solution was injected into the distracted area. In the
      group III, powder of chitosan microspheres and hGH were mixed with a 1-ml volume
      of hyaluronic acid to make an injectable form, and it was implanted into the
      distracted area. In group IV, powder of chitosan microsphere-encapsulated hGH was
      mixed with a 1-ml volume of hyaluronic acid. A total of 1-ml volume of the
      solution mix was implanted into the distracted area. Five dogs in each group
      (total of 20 dogs) were killed 3 weeks after completion of distraction. Twenty
      eight dogs were killed at 6 weeks. Bone mineral density was 13.1% of the
      contralateral normal mandible at 3 weeks and 29.6% at 6 weeks in group I, 16.4%
      at 3 weeks and 40.4% at 6 weeks in group II, 16.6% at 3 weeks and 45.95% at 6
      weeks in group III, and 29.6% at 3 weeks and 66.7% at 6 weeks in group IV. The
      mean three-point failure load was 16.1% in the control group, 34.7% in group II,
      41.5% in group III, and 52.1% in group IV compared with the intact contralateral
      mandible, with statistical significance. In the histological findings, new bone
      was generated in all groups. In group IV, the formation of active woven bone was
      observed throughout the distracted area at 6 weeks. The amount of new bone
      formation in the distracted zone was in the order of group IV, group III, group
      II, and the control group. In conclusion, these findings suggest that chitosan
      microsphere-encapsulated hGH seems to be quite effective in early bone
      consolidation in distraction osteogenesis.

PMID- 15167255
TI  - Comparison of membranous bone healing characteristics in fetal and postnatal
      periods: an experimental study.
AB  - In this experimental study, the postnatal and fetal membranous bone healing were
      investigated radiologically, histologically and levels of growth factors. Sixteen
      sheep fetuses and 16 sheep were included in this study. In the fetal group, 5 mm
      diameter ostectomy, and a 10 mm osteotomy were created in 90th gestational day.
      In the postnatal group, similar ostectomy and osteotomies were created. In the
      early period, radiologically similar radiolucencies in the ostectomy areas were
      seen in both groups. Histologically, fetal bone healing was decreased in the
      early postoperative period. However, it was accelerated in further time points.
      Histomorphometric analyses revealed accelerated fetal bone healing. TGF-beta1
      levels were higher and then lower in early and late postoperative periods
      respectively in the fetal group. In the postnatal group, the levels of TGF-beta1
      were lower and the differences between two groups were statistically significant
      in all time points (p < 0.05). The FGF and PDGF levels in both areas were higher
      in early postoperative period whereas lower in the late period in both groups.
      However, the fetal FGF levels were higher compared to the postnatal group (p <
      0.05). The fetal PDGF levels were lower compared to the postnatal ones (p <
      0.05). In conclusion, the calvarial bone gap model at the end of the second
      trimester of gestation in the fetal sheep model proved useful in examining the
      membranous bone healing. Histologically, the process of fetal bone healing seems
      similar to that of postnatal healing, albeit at an accelerated rate.
      Histomorphometric evaluation is a valuable tool in the evaluation of bone
      formation and gives more objective information about the ratio of bone formation.

PMID- 15167256
TI  - Introduction of a novel internal spring-driven craniofacial bone distraction
      device.
AB  - A study of craniofacial bone distraction using an internal self-expanding bone
      device designed by the authors was performed in a young rabbit skull model. Ten
      30-day-old New Zealand white rabbits were divided into two groups: 5 underwent
      distraction with the device, and 5 served as controls. Serial cephalograms,
      defleshed skull measurements, and histological examinations were performed on the
      study animals. The distracted group demonstrated a significant midface
      lengthening and overbite compared with the control group. Histologically, more
      fibroblasts and osteoblasts were seen in the front nasal bone in the distracted
      group in comparison with the nondistracted controls. The self-expanding internal
      bone distractor can effectively lengthen certain facial bones in an animal model
      and avoid some of the disadvantages associated with the external distraction
      techniques. This new device offers clinical potential as a useful distraction
      technique, but further work is needed to determine the effects of continuous
      postoperative tension loads on bone healing, the amount of tension generated by
      certain spring loads and lengths, and the feasibility of applying this concept in
      confined bone spaces.

PMID- 15167257
TI  - Dove tail osteotomy in distraction osteogenesis of costochondral bone grafts in
      the mandible: a new concept.
AB  - To correct the malocclusion and facial asymmetry in patients with Pruzansky type
      III hemifacial microsomia after autogenous costochondral grafting during early
      childhood (two male and three female patients with an average age of 17.8 years),
      the technique of distraction osteogenesis with a three-dimensional device was
      used. Because of the missing periosteum of the transplanted rib and its
      relatively small height compared with the horizontal mandible, a dovetail
      geometrical pattern osteotomy was introduced to increase the osteotomy surface
      area, which by itself could enhance the amount of fibrin filaments between 30%
      and 40% in the hematoma occurring during the initial distraction process. These
      fibrin filaments are biofunctional guiding structures for the development of the
      microcallus, followed by enhancement of the bone-healing capacity, which allows
      optimal bone regeneration. Between 20 and 27 days (mean = 21.5 days) after
      distraction, complete ossification was noted radiographically in all treated
      patients. Based on our histological animal studies and clinical investigations,
      dove tail osteotomy enhances the osteotomized surface area and offers protection
      to the tension-sensitive structures in the center of the distraction zone. It
      increases early bone formation and mineralization adjacent to the center zone in
      the distraction gap. Therefore, the dove tail geometrical pattern in combination
      with distraction osteogenesis of autologous costochondral grafts in the treatment
      of congenital Pruzansky type III mandibular hypoplasia is strongly recommended.

PMID- 15167258
TI  - Use of the serratus anterior free flap to treat a recurrent oroantral fistula.
AB  - We describe the successful use of the serratus anterior free muscle flap to
      obliterate a recurrent oroantral fistula in a 39-year old male who 19 years
      before this surgery had sustained a high velocity impact to his right face with
      multiple subsequent corrective surgeries. There was no complication from the
      serratus anterior free flap surgery and no postoperative scapular winging. The
      serratus anterior muscle is a versatile flap and ideal for various defects. It
      should be considered for obliteration of oroantral fistulas when no local or
      regional tissue is available because of previous surgery or trauma.

PMID- 15167259
TI  - A split ostectomy of mandibular body and angle reduction.
AB  - Combined mandibular angle resection with angle-splitting ostectomy (ASO) is more
      effective than conventional simple or multistaged ostectomy. Removal of the outer
      cortex of the mandibular body by ASO lessens the protuberance of the masseter
      muscle. In this study, the anatomy of the mandibular canals in seven human
      cadavers was studied in detail, and a guideline for ASO and mandibular angle
      ostectomy was set up so as to avoid injury to the inferior alveolar nerve. The
      most vulnerable area of the inferior alveolar nerve is the line from the gonion
      (G) to the junction (O) of the intersecting vertical line along the anterior
      border of the ramus and the horizontal line on the alveolar crest because of the
      thin anterior distance (AD) between the buccal surface of the mandible and the
      outer wall of the mandibular canal. The resection line should not be above 17.5
      mm at the GO line to ensure a safe inferior distance, the distance between the
      inferior border of the mandible and the floor of the mandibular canal (21.6 +/-
      4.1 mm). The body of the mandible was less vulnerable to injury to the inferior
      alveolar nerve in ASO because of the relatively thicker AD at the second molar
      (8.3 mm) and first molar (6.8 mm). Pilot surgery was performed in five cadavers.
      The lateral cortex was safely split off, avoiding injury to the inferior alveolar
      nerve, and angle ostectomy was then done. This method was applied in two clinical
      cases without any complications. The "split ostectomy of mandibular body and
      angle reduction" is a new and safe method of avoiding the injury to the inferior
      alveolar nerve.

PMID- 15167260
TI  - Amniotic band sequence: the use of bone grafting and distraction osteogenesis.
AB  - Distraction has proven to be a useful technique in cases of severe bone
      deficiency in the craniofacial skeleton. This is a report of its use in the
      treatment of a child affected by amniotic band sequence. This 5 year old Hispanic
      female presented with transverse deficiences of one lower extremity and both
      upper extremities. Additionally, she was missing the mandible and overlying soft
      tissue from ramus to ramus. Although free fibula transfer was a possibility, due
      to the presence of only one lower extremity, it was elected to utilize the
      technique of distraction. After preliminary bone grafting to unite these two
      hemimanibles, the bone graft was distracted bilaterally to create a neomandible.
      Following consolidation and removal of the distraction devices, the child was
      markedly improved despite what appeared to be a pathologic fracture in the region
      of the mandibular angle. Repeat distraction was planned.

PMID- 15167261
TI  - Innervation of the temporalis muscle for selective electrical denervation.
AB  - Bilateral hypertrophy of the temporal muscle can give the impression of an
      aggressive and violent facial appearance. The authors performed closed selective
      denervation of the deep temporal nerve using electrocauterization. Before the
      procedure, precise anatomical knowledge of the deep temporal nerve is mandatory.
      Sixteen hemifaces of Korean cadavers were dissected. To standardize the position
      of the anterior division of the deep temporal nerve, we recorded the distance
      from six anatomical landmarks to the nerve. In 19% (3 of 16) of cadavers, one
      deep temporal nerve was observed, and in the remainder, two deep temporal nerves
      were identified. In all our specimens, a mean of three (range: 1-4) temporal
      branches also arose from the buccal nerve. One temporal branch arising in common
      with the masseteric nerve was observed in 2 of 15 of our specimens. On the
      infratemporal crest, the distances from the anterior division of the deep
      temporal nerve to the posterior division of the deep temporal nerve and to the
      masseter nerve were 4.7 +/- 0.9 mm (range: 3-6 mm) and 8.3 +/- 1.1 mm (range: 6
      10 mm), respectively. On the superior surface of the zygomatic arch, the distance
      from the most concave point of the zygomatic bone (point A) to the anterior
      division of the deep temporal nerve was 19.4 +/- 1.2 mm (range: 18-21 mm). On the
      inferior surface of the zygomatic arch, the distance from the prominent point of
      the condylar process of the mandible to the anterior division of the deep
      temporal nerve was 22.3 +/- 1.6 mm (range: 22-25 mm). Great consistency in the
      position of the anterior division of the deep temporal nerve was shown. The
      results of this study could provide a basis for closed selective denervation of
      the anterior division of the deep temporal nerve using electrocauterization.
      Clinical application is needed.

PMID- 15167265
TI  - Re: Regulation of protein kinase C isozyme and calcineurin expression in
      isoproterenol-induced cardiac hypertrophy.

PMID- 15167267
TI  - Benidipine reduces myocardial infarct size involving reduction of hydroxyl
      radicals and production of protein kinase C-dependent nitric oxide in rabbits.
AB  - Japanese white rabbits underwent 30 minutes of ischemia and 48 hours of
      reperfusion. Benidipine (3 or 10 microg/kg, i.v.) was administered 10 minutes
      before ischemia with and without pretreatment with L-NAME (10 mg/kg, i.v., a NOS
      inhibitor), chelerythrine (5 mg/kg, i.v., a PKC blocker) or 5-HD (5 mg/kg, i.v. a
      mitochondrial KATP channel blocker), genistein (5 mg/kg, i.v. a protein tyrosin
      kinase blocker). SNAP (2.5 mg/kg/min x 70 minutes, i.v., an NO donor) was also
      administered 10 minutes before ischemia. Benidipine significantly reduced the
      infarct size in a dose-dependent manner (3 microg/kg: 29.0 +/- 2.7%, n = 8, 10
      microg/kg: 23.0 +/- 2.4%, n = 10) compared with the control (41.6 +/- 3.3%, n =
      10). This effect was completely blocked by L-NAME (39.9 +/- 3.6%, n = 8) and
      chelerythrine (35.5 +/- 2.4%, n = 8) but not by 5-HD (23.0 +/- 2.4%, n = 10) or
      genistein (24.6 +/- 3.1%, n = 10). SNAP also reduced the infarct size (24.6 +/-
      3.1%, n = 8). Benidipine significantly increased the expression of eNOS mRNA at
      30 minutes after reperfusion and significantly increased the expression of eNOS
      protein at 3 hours after reperfusion in the ischemic area of the left ventricle.
      Benidipine and SNAP significantly decreased myocardial interstitial 2,5-DHBA
      levels, an indicator of hydroxyl radicals, during ischemia and reperfusion.
      Benidipine increased myocardial interstitial NOx levels, which effect was blocked
      by chelerythrine, during 0 to 30 minutes and 150 to 180 minutes after
      reperfusion. Benidipine reduces the infarct size through PKC-dependent production
      of nitric oxide and decreasing hydroxyl radicals but not through involving
      protein tyrosine kinase or mitochondrial KATP channels in rabbits.

PMID- 15167268
TI  - Phenylalanine improves dilation and blood pressure in GTP cyclohydrolase
      inhibition-induced hypertensive rats.
AB  - GTP cyclohydrolase (GTPCH), the rate-limiting enzyme in the production of the
      nitric oxide synthase cofactor tetrahydrobiopterin (BH4), is partly regulated by
      the GTPCH feedback regulatory protein (GFRP). GFRP can inhibit GTPCH by end
      product negative feedback, and L-phenylalanine (L-Phe) reverses this inhibition
      and increases BH4 biosynthesis in vitro. We hypothesized that L-Phe would
      increase endothelium-dependent relaxation and decrease blood pressure in rats
      made hypertensive by GTPCH inhibition. Di-amino-hydroxypyrimidine (DAHP, 10
      mmol/L), a known inhibitor of GTPCH, was given with or without L-Phe or D-Phe (2
      mmol/L) in the drinking water of rats for 3 days and blood pressure was measured
      via tail-cuff. Endothelium-intact aortic segments were hung in organ chambers for
      measurement of isometric force generation. Systolic blood pressure was increased
      significantly in DAHP-treated rats compared with controls. The addition of L-Phe
      attenuated the hypertensive effect, whereas D-Phe had no effect. Acetylcholine-
      and A23187-induced relaxation was decreased in aortas from DAHP-treated rats
      compared with controls, but was restored in aortas from DAHP+L-Phe-treated rats.
      Following NOS inhibition, sensitivity to sodium nitroprusside was increased in
      aortas from DAHP-treated rats, but restored in DAHP+L-Phe-treated rats. These
      results suggest that L-Phe can reverse GTPCH inhibition in vivo leading to
      increased vasodilation and decreased blood pressure.

PMID- 15167269
TI  - ET-A receptor activity restrains coronary blood flow in the failing heart.
AB  - Circulating levels of the potent vasoconstrictor peptide endothelin-1 (ET-1) are
      increased in congestive heart failure (CHF). Coronary blood flow and myocardial
      oxygen consumption (MVO2) are decreased in some models of CHF. This study tested
      the hypothesis that ET-1 induced coronary vasoconstriction limits oxygen
      availability in the failing heart. The effects of selective ET-A receptor
      blockade with BQ610 (5 microg/min, intracoronary) and selective ET-B receptor
      blockade with BQ788 (5 microg/min, intracoronary) on coronary blood flow were
      examined at rest and during graded treadmill exercise in 8 dogs in which
      congestive heart failure (CHF) had been produced by rapid ventricular pacing for
      three to four weeks. In animals with CHF, ET-B receptor blockade caused no change
      in left ventricular (LV) pressure or coronary blood flow. In contrast, ET-A
      blockade with BQ610 resulted in modest significant increases of coronary blood
      flow at rest (from 22.4 +/- 2.1 to 27.9 +/- 3.0 mL/min) and during two exercise
      stages (from 26.9 +/- 2.0 to 30.7 +/- 1.9 during stage 1 exercise and from 28.5
      +/- 2.0 to 31.7 +/- 1.3 mL/min during stage 2; all P < 0.05), with an upward
      shift in the relationship between coronary flow and rate-pressure product. The
      increase in coronary flow produced by ET-A blockade was not associated with an
      increase of either myocardial oxygen uptake or LV dP/dt. Thus, although ET-A
      receptor blockade caused a modest increase in coronary flow, this did not result
      in an increase of MVO2, implying that ET-A-mediated coronary vasoconstriction did
      not limit oxygen uptake by the failing heart.

PMID- 15167270
TI  - The serotonin transporter is present and functional in peripheral arterial smooth
      muscle.
AB  - We tested the hypothesis that the 5-HT transporter (5-HTT) is present and
      functional in peripheral arterial smooth muscle. In aorta and mesenteric
      resistance arteries, real time RT-PCR and western analyses indicated the presence
      of 5-HTT mRNA and a 74 kDa 5-HTT protein. Immunohistochemistry localized the
      transporter to smooth muscle and endothelial cells. 5-HT and the metabolite 5
      hydroxyindole acetic acid (5-HIAA) were detected in aorta, carotid, and superior
      mesenteric arteries using HPLC; the MAOA inhibitor pargyline significantly
      increased (over 400%) arterial 5-HT concentration. 5-HT was taken up by arteries
      in a time-dependent manner and uptake was independent of the endothelium,
      sympathetic nerves, and norepinephrine transporter. 5-HT-induced contraction of
      normal aorta was potentiated by the 5-HTT inhibitor fluvoxamine. A change in
      arterial 5-HTT function occurs in deoxycorticosterone (DOCA)-salt hypertension as
      the potency and threshold of 5-HT in contracting aorta from the DOCA-salt rat was
      increased by fluoxetine and fluvoxamine (1 micromol/L; DOCA fluvoxamine -log EC50
      [mol/L] = 6.85 +/- 0.08, DOCA-control = 6.44 +/- 0.08); expression of transporter
      was significantly increased in aorta of DOCA salt rats (145% Sham). These studies
      show for the first time the presence of the 5-HTT in peripheral arterial smooth
      muscle and raise the question as to the function of the 5-HTT in regulating
      peripheral effects of 5-HT.

PMID- 15167271
TI  - Myocardial protection after systemic application of L-arginine during
      reperfusion.
AB  - The L-arginine-nitric oxide (NO) pathway plays an important role in ischemia
      reperfusion injury. In the present study we investigated the role of NO-precursor
      L-arginine on cardiac and pulmonary function after reversible hypothermic
      ischemia. Twelve anesthetized dogs underwent cardiopulmonary bypass. After 60
      minutes of hypothermic cardiac arrest, reperfusion was started with application
      of either saline vehicle (control, n = 6) or L-arginine (40 mg/kg i.v. bolus then
      3 mg/kg i.v. infusion during the first 20 minutes of reperfusion, n = 6). The
      vasodilative response to acetylcholine was significantly higher in the L-arginine
      group (P < 0.05). The preload recruitable stroke work of the left ventricle
      decreased significantly after reperfusion, however remained unchanged in the L
      arginine group. Arterial blood gas analysis did not show any difference between
      the two groups. Plasma L-arginine concentration reached peak level at 20 minutes
      of administration (675.0 +/- 66.6 versus 207.7 +/- 14.5 in the L-arginine group,
      P < 0.05) and returned to baseline at 40 minutes, while in the control group
      remained unchanged during ischemia and reperfusion (276.2 +/- 71.6 versus 283.8
      +/- 38.5, P < 0.05). Plasma nitrite concentration followed L-arginine changes
      parallel, however nitrate levels increased slower. Supplementation with L
      arginine during reperfusion prevents myocardial and endothelial dysfunction,
      however does not have any overriding effect on pulmonary function. Considerably
      rapid elimination of plasma L-arginine was demonstrated during early reperfusion.

PMID- 15167272
TI  - Minoxidil attenuates ischemia-induced apoptosis in cultured neonatal rat
      cardiomyocytes.
AB  - The effects of minoxidil (a mitochondrial K+(ATP) channel opener) on ischemia
      induced necrosis and apoptosis were examined using a cardiomyocyte model of
      simulated ischemia, since mitochondrial K+(ATP) channel openers have been
      suggested to be involved in the mechanisms of cardioprotective action against
      ischemia/reperfusion injury. In the absence of minoxidil, simulated ischemia led
      to cellular release of creatine phosphokinase (CPK), morphologic degeneration,
      and beating cessation within 24 to 72 hours. Based on the Hoechst 33258 staining
      pattern, a significant number of cells placed in sealed flasks underwent
      apoptosis. Myocytes treated with 5 microM of minoxidil failed to alter the degree
      of ischemia-induced CPK loss for 48 to 72 hours. However, minoxidil treatment
      prevented the loss of beating function in many of the ischemic cells, and
      attenuated the decline in intracellular ATP content after a 48-hour ischemic
      incubation. The number of nuclear fragmentation was significantly reduced in
      minoxidil-treated cells after a 72-hour ischemic insult compared with untreated
      ischemic cells. This effect was blocked by the mitochondrial K+(ATP) channel
      antagonist 5-HD. The data suggest that minoxidil renders the cell resistant to
      ischemia-induced necrosis and apoptosis. The beneficial effects of minoxidil
      appear to be related to the opening of mitochondrial K+(ATP) channels.

PMID- 15167273
TI  - Partial agonism of taprostene at prostanoid IP receptors in vascular preparations
      from guinea-pig, rat, and mouse.
AB  - This study investigates whether incomplete relaxation of vascular smooth muscle
      preparations induced by the prostacyclin analogue taprostene is due to partial
      agonism at prostanoid IP receptors. In the presence of the prostanoid EP4
      receptor antagonist AH 23848, 3 microM taprostene induced 45% relaxation of
      phenylephrine-contracted guinea-pig saphenous vein rings and displaced log
      concentration-response curves for the prostacyclin analogues AFP-07, TEI-9063,
      and cicaprost to the right, parallel to their predicted addition curves. In
      contrast, taprostene interacted additively with prostaglandin E2 (PGE2), ONO-AE1
      259 (selective EP2 agonist), and acetylcholine. Similarly, on rat tail artery
      contracted with phenylephrine, 3 microM taprostene (20% relaxation) opposed AFP
      07- but not PGE2-induced relaxation. However, under U-46619-induced tone (AH
      23848 absent), taprostene antagonized AFP-07 and cicaprost more than TEI-9063,
      suggesting that the latter has more than one relaxation mechanism. The presence
      of a sensitive EP3 contractile system in mouse aorta interfered with IP receptor
      mediated relaxation. By generating tone with phenylephrine and the potent EP3
      agonist sulprostone, it was possible to show that 3 microM taprostene (15%
      relaxation) selectively opposed relaxations induced by AFP-07, TEI-9063, and
      cicaprost. Our experiments indicate that taprostene is a partial agonist at
      prostanoid IP receptors, and may be a lead to an IP receptor antagonist.

PMID- 15167274
TI  - Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, blocks
      vascular smooth muscle cell populated-collagen lattice contraction.
AB  - Constrictive arterial remodeling plays a major role in lumen narrowing following
      angioplasty. We investigated the effect of pitavastatin, a 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA) reductase inhibitor, on vascular smooth muscle cell
      (SMC)-populated collagen lattice contraction, an in vitro model of vascular
      contraction. Type I collagen gel contraction by SMCs, which are cultured in
      collagen gel, was used as a model of vascular remodeling. Pitavastatin
      pretreatment inhibited 10% serum- or platelet-derived growth factor-BB (PDGF)
      induced SMC-mediated collagen lattice contraction in a concentration-dependent
      manner. The effect of pitavastatin was prevented by mevalonate or geranylgeranyl
      pyrophosphate, but not by squalene, a precursor of cholesterol, or farnesyl
      pyrophosphate. The serum- or PDGF-induced SMC-mediated collagen gel contraction
      was inhibited by GGTI-298, a geranylgeranyltransferase inhibitor, C3 exoenzyme,
      an inhibitor of Rho, or Y27634, a Rho kinase inhibitor, but not by FTI-277, a
      farnesyltransferase inhibitor. Serum or PDGF treatment increased the stress fiber
      organization in SMCs, which was blocked by the pitavastatin pretreatment.
      Pitavastatin had no effect on the serum- and PDGF-induced lamelliopodia extension
      of SMC. These results may suggest that pitavastatin attenuates SMC-mediated
      collagen gel contraction probably via an inhibition of geranylgeranylated Rho
      protein and a disruption of actin cytoskeletal reorganization.

PMID- 15167275
TI  - Nitric oxide and inactivation of the endothelium-dependent contracting factor
      released by acetylcholine in spontaneously hypertensive rat.
AB  - In the aorta of the spontaneously hypertensive rat (SHR), endothelium-dependent
      contractions are enhanced by inhibitors of NO synthase and scavengers of NO, but
      not by methylene blue, an inhibitor of guanylyl cyclase, suggesting that the
      endothelium-derived contracting factor (EDCF) interacts chemically with NO and is
      inactivated by the latter. However, in view of the relative lack of specificity
      of methylene blue this hypothesis was re-examined. Acetylcholine-induced
      endothelium-dependent contractions of isolated rings of SHR aorta were
      significantly and similarly potentiated by two NOS inhibitors, by two
      structurally different NO scavengers, by two inhibitors of guanylate cyclase ODQ
      and NS2028, but to a lesser extent by methylene blue. The contraction of the
      isolated rat trachea in response to methacholine and the contraction of the rat
      aorta in response to both 8-isoprostane and KCl were inhibited significantly by
      methylene blue. Methylene blue binds to the M3 muscarinic receptor subtype but
      not to the TP receptor. Therefore, methylene blue is an antagonist of the M3
      muscarinic receptor subtype, involved in the release of EDCF, and a non-specific
      inhibitor of TP receptor-mediated contractions, the receptor involved in the
      action of EDCF. These inhibitory effects of methylene blue are likely to
      counteract the effect of the inhibition of soluble guanylate cyclase. These
      results rule out the hypothesis according to which NO would chemically inactivate
      EDCF.

PMID- 15167276
TI  - Raloxifene improves coronary perfusion, cardiac contractility, and myocardial
      metabolism in the ischemic heart: role of phosphatidylinositol 3-kinase/Akt
      pathway.
AB  - The purpose of this study is to examine whether raloxifene, one of the selective
      estrogen receptor modulators, could improve myocardial ischemia and to assess the
      mechanisms involved. In open-chest beagle dogs anesthetized by intravenous
      infusion of sodium pentobarbital, the left anterior descending coronary artery
      (LAD) was perfused from the left carotid artery through an extracorporeal bypass
      tube. Raloxifene was infused into the LAD through the bypass tube under either
      ischemic or non-ischemic conditions. In the non-ischemic heart, raloxifene had no
      effect on coronary blood flow, fractional shortening, and myocardial metabolism.
      However, raloxifene caused an acute increase in both coronary blood flow and
      fractional shortening, and also improved myocardial anaerobic metabolism in the
      ischemic heart. These effects were partially attenuated by pretreatment with
      either L-NAME or wortmannin and were completely abolished by ICI182780 (an
      estrogen receptor antagonist) or L-NAME plus charybdotoxin (a blocker of Ca
      activated K channels). Raloxifene also increased both Akt activity and the NO
      level, with these changes being completely abrogated by pretreatment with
      wortmannin. These results demonstrated that raloxifene improves coronary
      perfusion, cardiac contractility, and myocardial metabolism by release of NO and
      opening of Ca-activated K channels in the ischemic heart, and that NO production
      is mediated by the phosphatidylinositol 3-kinase/Akt pathway.

PMID- 15167277
TI  - Effect of clonidine on cardiac norepinephrine spillover in isolated rat heart.
AB  - The purpose of this study is to determine the effect of clonidine on cardiac
      norepinephrine spillover utilizing an isolated rat heart preparation with
      attached cardiac sympathetic nerves. Following a 20-minute stabilization period,
      the sympathetic ganglion for each heart preparation was electrically stimulated
      with 10V and 2 Hz for 30 seconds (S1: 60 pulses). Heart rate, left ventricular
      developed pressure, and coronary perfusion pressure was allowed to return to
      baseline and the perfusate was randomly switched to Krebs buffer containing one
      of two treatments: placebo or clonidine (1 microM). After 10 minutes of
      treatment, the sympathetic ganglion was again electrically stimulated with 10V
      and 2 Hz for 30 seconds (S2: 60 pulses). The perfusate exiting the heart before,
      during, and after each electrical stimulation was collected for the determination
      of cardiac norepinephrine spillover. Clonidine administration significantly
      reduced cardiac norepinephrine spillover by approximately 50% (P < 0.05) and was
      associated with a 36% reduction in heart rate (P < 0.05). These findings provide
      evidence that clonidine can directly suppress NE spillover from cardiac
      sympathetic nerve terminals. Thus, suppression of cardiac NE by clonidine may be
      due to stimulation of presynaptic alpha2-adrenergic receptors or imidazoline
      subtype I receptors located on cardiac sympathetic nerve terminals. Results from
      our study demonstrate a reduction in cardiac NE spillover by clonidine and
      provide additional evidence that it can directly suppress peripheral sympathetic
      activity in that our results were obtained utilizing an isolated perfused heart
      preparation with attached cardiac sympathetic nerves devoid of any CNS input.

PMID- 15167278
TI  - Different role of nitric oxide and endothelium-derived hyperpolarizing factor in
      endothelium-dependent hyperpolarization and relaxation in porcine coronary
      arterial and venous system.
AB  - OBJECTIVE: We compared the basal and bradykinin (BK)-induced NO release and
      endothelium-derived hyperpolarizing factor-mediated function between coronary
      arteries and cardiac veins. METHODS AND RESULTS: Isolated coronary vessels (large
      arteries, cardiac veins as well as microvessels) were studied. An NO-specific
      electrode and a conventional intracellular glass microelectrode were used to
      directly measure NO released from endothelial cells and hyperpolarization of
      smooth muscle cells in conduit coronary vessels. The basal and BK-induced release
      of NO was 14.2 +/- 2.0 nmol/L and 237.1 +/- 27.2 nmol/L (n = 8) in the artery,
      significantly greater than in veins (8.0 +/- 1.1 nmol/L and 135.6 +/- 14.5
      nmol/L, n = 8, P < 0.01). The BK-induced hyperpolarization was significantly
      reduced by N-nitro-L-arginine, indomethacin, and hemoglobin in both arteries and
      veins and was greater in the arteries. The EDHF-mediated relaxation was
      significantly higher in the arteries than in veins, greater in microveins than in
      large veins, and almost abolished by charybdotoxin and apamin. CONCLUSIONS: Both
      NO and EDHF are involved in the regulation of the vascular tone in the coronary
      arterial and venous systems but the amount of NO release and the EDHF-mediated
      relaxation and associated hyperpolarization are less significant in the vein than
      in the artery in the coronary system.

PMID- 15167279
TI  - Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial
      fibrosis and over-expression of connexin43 in a canine model of atrial pacing
      induced left ventricular dysfunction.
AB  - Effects of enalapril on a canine model of atrial pacing-induced atrial
      fibrillation (AF) with rapid ventricular responses were determined. METHODS: Four
      weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with
      placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial
      effective refractory period (ERP), P-wave width, duration of AF, and left
      ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length
      was determined by spectral analyses of fibrillation waves. Quantitative analysis
      of histology was added. RESULTS: After 4 weeks of pacing, P-wave width was longer
      in Group I than in Group II, and the duration of induced AF was significantly
      longer in Group I (59.6 +/- 66.3 seconds) than in Group II (3.6 +/- 3.4 seconds,
      P < 0.05). AF cycle length was longer in Group I than in Group II despite similar
      shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was
      not different between the two groups. LVEF similarly decreased in both groups.
      Interstitial fibrosis and expression of connexin43 was greater in Group I than in
      Group II (interstitial fibrosis, 9.2 +/- 8.4 versus 1.9 +/- 2.1%, P < 0.05;
      connexin43, 5.3 +/- 2.2 versus 1.1 +/- 1.1%, P < 0.05). CONCLUSIONS: Enalapril
      suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by
      suppressing interstitial fibrosis, connexin43 over-expression and conduction
      delay.

PMID- 15167280
TI  - Candesartan prevents myocardial fibrosis during progression of congestive heart
      failure.
AB  - BACKGROUND: The goal of this study was to determine whether an Angiotensin II
      receptor antagonist, candesartan, prevents myocardial fibrosis more effectively
      than enalapril in animals with a non-ACE pathway during the progression of
      congestive heart failure (CHF). METHODS AND RESULTS: Dogs were randomly assigned
      to one of four groups: (1) rapid ventricular pacing (240 bpm); (2) concomitant
      candesartan cilexetil (1.5 mg/kg/d) and rapid pacing; (3) concomitant enalapril
      (1.9 mg/kg/d) and rapid pacing; (4) sham-operated control. The expression of
      collagen type I & III mRNA and the collagen volume fraction, which were
      significantly increased in the pacing-only group, were suppressed by both
      treatments; it was lower in the candesartan than the enalapril group. Although
      there were no differences in the LV stiffness coefficient (beta) among all pacing
      groups, the absolute changes in beta from the control values were smaller in the
      candesartan group, but not the enalapril group, compared with the rapid-pacing
      only group. CONCLUSIONS: The present study demonstrates that in animals with a
      non-ACE pathway, candesartan suppressed myocardial fibrosis during the
      progression of CHF in comparison with enalapril. Furthermore, candesartan
      prevented an increase in LV stiffness. These findings imply potential clinical
      applications for candesartan in the management of CHF to prevent myocardial
      fibrosis. Further prospective evaluation and clinical study will be necessary
      before deciding on the net benefits of candesartan in comparison to enalapril.

PMID- 15167282
TI  - Antiplatelet and antithrombotic activity of L-3-n-butylphthalide in rats.
AB  - 3-n-butylphthalide (NBP) is a potentially beneficial drug for the treatment of
      ischemic stroke with multiple actions on different pathophysiological processes.
      In the present study, the effect of l-, d-, and dl-NBP was investigated on ADP-,
      collagen-, and AA-induced platelet aggregation. l-NBP was the most potent among l
      , d-, and dl-NBP. At higher concentration the effect of dl-NBP on platelet
      aggregation was greater than that of l- or d-NBP alone. The ex vivo
      antiaggregatory activity of l-NBP 100mg/kg declined gradually after 2 hours, but
      a considerable antiplatelet activity was still observed 4h after l-NBP
      administration. NBP was given orally and resulted in a dose-dependent inhibition
      of thrombus formation. Of the two isomers, l-NBP was the most potent. It
      significantly protected mice from a mixture of collagen and epinephrine induced
      thromboembolic death. When 100 mg/kg of l-NBP were administered orally to rats,
      the bleeding time increased 2.1-fold compared with the control group. At the same
      dose, ex vivo platelet aggregation induced by ADP, collagen, and AA was inhibited
      by l-NBP and the antithrombotic effects of the compound were also observed. Thus,
      NBP exerts oral anti-platelet and anti-thrombotic efficacy without perturbing
      systemic hemostasis in rats. l-NBP is more potent than d- and dl-NBP as
      antiplatelet agent.

PMID- 15167281
TI  - Peroxisome proliferator-activated receptor-gamma ligands ameliorate experimental
      autoimmune myocarditis associated with inhibition of self-sensitive T cells.
AB  - OBJECTIVE: Recent evidence has suggested that peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) serves as a negative regulator in the immune system.
      In the present study, we investigated the expression of PPAR-gamma and the effect
      of PPAR-gamma ligands on experimental autoimmune myocarditis (EAM). METHODS AND
      RESULTS: Experimental autoimmune myocarditis was induced in Lewis rats by
      immunization with porcine cardiac myosin. PPAR-gamma ligands 15-deoxy-Delta-PGJ2
      200 microg x kg(-1) x d(-1) by ip and pioglitazone 10 mg x kg(-1) x d(-1) by oral
      were administered for 3 weeks. PPAR-gamma expression was upregulated in
      myocarditis and the enhanced PPAR-gamma expression was prominently stained in the
      nuclear and perinuclear regions of the positive-stained cells in the inflammatory
      lesions. Administration of PPAR-gamma ligands markedly reduced the severity of
      myocarditis, as indicated by the heart weight/body weight ratio, pericardial
      effusion scores, macroscopic scores, and microscopic scores. The upregulated PPAR
      gamma expression was also reduced by PPAR-gamma ligands treatment. In addition,
      PPAR-gamma ligands suppressed the proliferative response and interferon-gamma
      production of T cell-enriched splenocytes from rats with EAM. Furthermore, the
      cytotoxic activity and myocarditogenic potential of these T cells were inhibited
      by PPAR-gamma ligands treatment. CONCLUSIONS: PPAR-gamma ligands ameliorate EAM
      associated with inhibition of expansion and activation of the self-sensitive T
      cells. These results suggest that PPAR-gamma ligands may have the potential to
      modulate human inflammatory heart diseases as myocarditis.

PMID- 15167283
TI  - Transport of HIV protease inhibitors through the blood-brain barrier and
      interactions with the efflux proteins, P-glycoprotein and multidrug resistance
      proteins.
AB  - HIV protease inhibitors (HPIs) have limited penetration into the brain. This poor
      transport through the blood-brain barrier is mainly due to active efflux by
      proteins such as P-glycoprotein (P-gp) preventing drugs from clearing the brain
      of the virus. The present paper focuses on cerebral uptake of HPIs and
      interactions between HPIs and efflux proteins, either as substrates or
      modulators. Most of the studies described HPIs as P-gp substrates. Studies are
      more controversial when investigating HPIs as inhibitors of P-gp. HPIs seem to be
      able to inhibit efflux proteins of in vitro cell models but with limited
      consequences in vivo. Moreover, after repeated administrations of HPIs, most of
      them are also able to induce the expression and functionality of P-gp. For these
      reasons, certain combinations of HPIs may not efficiently increase brain uptake
      of HPIs as would combinations of more potent efflux inhibitors.

PMID- 15167284
TI  - Mother-to-child transmission of HIV-1: strong association with certain maternal
      HLA-B alleles independent of viral load implicates innate immune mechanisms.
AB  - The transmission of HIV-1 from mother to child during pregnancy is unlike other
      types of HIV-1 transmission because the child shares major histocompatibility
      complex (MHC) genes with the mother during a time while the mother is induced to
      tolerate the paternally derived fetal MHC molecules, in part through natural
      killer (NK) recognition of MHC polymorphisms. The relevance of these immune
      mechanisms to HIV-1 transmission was assessed by determining the HLA-B alleles of
      mother and infant. Almost half (48%) of mothers who transmitted with low viral
      loads had HLA-B*1302, B*3501, B*3503, B*4402, or B*5001 alleles, compared with 8%
      of nontransmitting mothers (P=0.001). Conversely, 25% of mothers who did not
      transmit despite high viral loads had B*4901 and B*5301, vs. 5% of transmitting
      mothers (P=0.003), a pattern of allelic involvement distinct from that
      influencing HIV-1 infection outcome. The infant's HLA-B alleles did not appear
      associated with transmission risk. The HLA-B*4901 and B*5301 alleles that were
      protective in the mother both differed respectively from the otherwise identical
      susceptibility alleles, B*5001 and B*3501, by 5 amino acids encoding the ligand
      for the KIR3DL1 NK receptor. These results suggest that the probable molecular
      basis of the observed association involves definition of the maternal NK
      recognition repertoire by engagement of NK receptors with polymorphic ligands
      encoded by maternal HLA-B alleles, and that the placenta is the likely site of
      the effect that appears to protect against transmission of maternal HIV-1 through
      interrelating adaptive and innate immune recognition.

PMID- 15167285
TI  - Persistent apoptosis in HIV-1-infected individuals receiving potent
      antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.
AB  - CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis.
      Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like
      IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL
      (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and
      Fas were determined in 55 HIV-1 infected persons treated with highly active
      antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA
      remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and
      CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a
      poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or
      proapoptotic markers in cultured PBMCs and T lymphocytes. The significant
      relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery
      suggests that persistent apoptosis may impede immune restoration.

PMID- 15167286
TI  - Human herpesvirus 8/Kaposi sarcoma herpesvirus cell association during evolution
      of Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is associated with a herpesvirus (HHV-8/KSHV), which
      expresses a latency-associated nuclear antigen (LANA). The histopathology of KS
      is characterized by angiogenesis, inflammatory cells, and the development of
      CD34+ tumor spindle cells (SCs). However, the cellular basis for the recruitment
      and dissemination of HHV-8 during the development of KS lesions is not clear.
      Twenty-nine KS biopsies with AIDS (AKS, n=22) and without HIV infection (endemic
      KS or EKS, n=7) were immunostained by a triple antibody method to characterize
      HHV-8-infected and noninfected (LANA+/-) CD34+ SCs, infiltrating CD3+, CD68+,
      CD20+, and CD45+ leukocytes as well as proliferating (Ki67+) cells. The
      CD34+/LANA+ SCs were more frequent in late (nodular) as compared with early
      (patch/plaque) KS stages. However, in late AKS 36.0% of SCs (median of 11 cases)
      were CD34+/LANA- compared with 20.7% in early cases (median of 11 cases).
      Furthermore, both AKS and EKS showed, at all stages, a small (4.1-6.5%)
      population of LANA+/CD34- cells. Proliferating Ki67+ cells were seen (4.5-11.5%)
      at all KS stages, and were usually more frequent in early AKS, but no significant
      difference was observed between nodular AKS and EKS. Most of the proliferating
      cells in the KS lesions were LANA+/CD34+ but a small fraction was LANA+/CD34-.
      Lesional CD68+ and CD3+ cells varied between AKS (7.3 and 5.2%, respectively) and
      EKS (4.9 and 3.1%, respectively) but were not clearly stage related. No LANA+
      cells were CD3+, CD20+, or CD45+ and very few (<0.5%) were CD68+. These results
      indicate that not all CD34+ KS SCs were LANA+, suggesting recruitment of
      noninfected SCs to the lesions. Cell proliferation in general was much higher in
      early as compared with the late AKS stages. LANA+ SCs could have a proliferative
      advantage as suggested by higher frequency of cycling (Ki67+) LANA+ SCs. Few
      macrophages but no lymphocytes are LANA+.

PMID- 15167287
TI  - Long-term efficacy and safety of atazanavir with stavudine and lamivudine in
      patients previously treated with nelfinavir or atazanavir.
AB  - The purpose of the study was to determine long-term efficacy, safety, and
      tolerability of atazanavir plus stavudine/lamivudine in 346 HIV-infected patients
      previously treated with atazanavir or nelfinavir. BMS AI424-044 is an ongoing,
      multicenter, international, open-label, rollover/switch study initiated in June
      2001. Patients completing >or=48 weeks in trial BMS AI424-008 with a plasma HIV
      RNA viral load <10,000 copies/mL were eligible to continue on atazanavir (400 or
      600 mg) or to switch from nelfinavir to atazanavir (400 mg) once daily. Antiviral
      efficacy, change in CD4 cell counts, and effect on lipid parameters were
      measured. After 24 weeks of atazanavir use in BMS AI424-044, 83%, 85%, and 87% of
      the atazanavir 400-mg, atazanavir 600-mg, and nelfinavir-to-atazanavir-switched
      patients, respectively, had HIV RNA levels <400 copies/mL compared with 76%, 76%,
      and 63%, respectively, at week 48 of BMS AI424-008. Atazanavir-treated patients
      showed minimal changes in lipid levels compared with baseline. Patients switched
      from nelfinavir to atazanavir showed significant mean percent decreases in total
      cholesterol (-16%), fasting low-density lipoprotein cholesterol (-21%), and
      fasting triglycerides (-28%) (P<0.0001) by week 12 of atazanavir treatment. No
      new safety issues were identified, and the overall incidence of treatment
      emergent adverse events during BMS AI424-044 was comparable across treatment
      groups. Atazanavir was safe, tolerable, and effective during extended use and in
      patients switched from nelfinavir. Extended atazanavir use resulted in continued
      viral suppression and lipid changes that were not clinically relevant. In
      virologically suppressed nelfinavir-treated patients switched to atazanavir,
      virologic improvement continued, whereas nelfinavir-induced lipid elevations were
      reversed within 12 weeks, approaching pretreatment values.

PMID- 15167288
TI  - Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a
      Thai population with HIV infection.
AB  - We compared the long-term immunologic and virologic efficacy of the dual- and
      triple-nucleoside therapy for HIV infection. This was a retrospective analysis of
      2 randomized clinical trials in antiretroviral-naive patients. In the dual
      nucleoside group, 15 started with didanosine (ddI) monotherapy and then added
      stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and
      53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside
      group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not
      failing were randomized to immediate (before treatment failure) versus delayed
      (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or
      vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure
      was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000
      copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48
      received the new treatment as in the immediate switching group. Hydroxyurea was
      added to the last treatment regimen if patients failed after week 96. CD4 count
      and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50
      copies/mL) at week 144 were analyzed by intention to treat. Compared with the
      dual-nucleoside group, the triple-nucleoside group had a higher proportion of
      patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median
      CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration
      of response, defined as the time from onset of viral suppression (<500 copies/mL)
      to the time of treatment failure (the first of 2 consecutive HIV-1 RNA
      measurements >500 copies/mL never followed by 2 consecutive visits showing
      suppressible viremia to <500 copies/mL) or discontinuation from the study (144
      weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that
      significant predictors for treatment success, defined as a plasma viral load <50
      copies/mL at week 144, were asymptomatic clinical status at enrollment, a
      baseline plasma viral load <or=30,000 copies/mL, treatment with triple
      nucleosides, and a viral load response of <500 copies/mL by week 12. Triple
      nucleoside therapy with ZDV, 3TC, and ddI or d4T, 3TC, and ABC in patients with
      HIV infection is more effective in inducing a sustained virologic response than
      the dual combinations of ZDV and 3TC or ddI and d4T.

PMID- 15167289
TI  - Long-term CD4+ T-cell response to highly active antiretroviral therapy according
      to baseline CD4+ T-cell count.
AB  - Current treatment guidelines for HIV infection recommend a relatively late
      initiation of highly active antiretroviral therapy (HAART). Nevertheless, there
      is still a concern that immune recovery may not be as complete once CD4+ T cells
      have decreased below a certain threshold. This study addressed the long-term
      response of CD4+ T-cell counts in patients on HAART and analyzed the influence of
      baseline CD4+ T-cell counts, baseline viral load, and age. An observational
      analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic
      HIV-1-infected patients who started treatment consisting of at least 3 drugs in
      or after 1996 was performed. Patients were classified in 4 groups according to
      baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and
      >or=500 cells/mm3. The main outcome measures were proportion of patients with
      CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell
      recovery. Patients were followed-up for a median of 173 weeks (interquartile
      range [IQR], 100-234). There were no differences in follow-up between the 4
      groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3
      (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group
      with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a
      last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75
      0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3,
      200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of
      having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95%
      CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI,
      0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349
      cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T
      cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was
      statistically significant and was maintained for up to 4 years of follow-up. This
      increase seemed to slow down after approximately 3 years and reached a plateau
      after 4-5 years of follow-up even in patients who achieved and maintained viral
      suppression in plasma. Long-term immune recovery is possible regardless of
      baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T
      cell count <200 cells/mm3 have poorer immunologic outcome as measured by the
      proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last
      determination. It seems that the immune recovery slows down after approximately 3
      years of HAART and reaches a plateau after 4-5 years of HAART.

PMID- 15167290
TI  - Contraceptive use in HIV-positive women.
AB  - The objective was to describe contraceptive use in women with HIV infection in
      France over the past decade. The study included 575 sexually active women of
      reproductive age, who knew the serologic status of their steady partners. It is
      part of a prospective observational study initiated in 1993 that was designed to
      investigate the gynecologic status of HIV-infected women. Women answered a
      standardized questionnaire about contraceptive use and sexual activity at each
      semiannual visit. Multivariate models were used to investigate parameters
      associated with the use of contraceptive methods. Contraceptive use was reported
      in 91% of the visits of women with an HIV-seronegative partner and 69% of women
      with an HIV-seropositive partner (P=0.0001). Consistent condom use was higher in
      serodiscordant couples than in seroconcordant couples (odds ratio [OR]=6.1, 95%
      CI=0.1-0.2, P<0.001). The use of oral contraception and intrauterine devices was
      higher in seroconcordant than in serodiscordant couples (OR=2.1, 95% CI=.5-2.9,
      P<0.001). Among women with an HIV-seronegative partner, the use of oral
      contraception and intrauterine devices decreased after the introduction of highly
      active antiretroviral therapy in 1998 (P=0.02) and was higher in couples with
      inconsistent condom use (OR=2.0, 95% CI=1.3-3.3). These data emphasize that
      contraception counseling should include a discussion on reproductive issues as
      well as transmission of HIV and other sexually transmitted infections, taking
      into account the partner's serostatus.

PMID- 15167291
TI  - Knowledge about vaccines and willingness to participate in preventive HIV vaccine
      trials: a population-based study, Rakai, Uganda.
AB  - The purpose of the study was to assess knowledge and beliefs regarding vaccines
      and willingness to participate in HIV vaccine trials. A baseline survey assessed
      knowledge and attitudes toward vaccination and potential HIV vaccines among
      14,177 participants aged 15-49 years, in a population cohort. Willingness to
      participate in HIV-preventive vaccine trials was assessed during a follow-up
      survey 10 months later after providing community education on HIV vaccines.
      Knowledge of the preventive utility of vaccines was high (71%), but higher in men
      than women (P<0.001), and increased with education levels (P<0.001). Vaccines
      were considered appropriate for children and women (99 and 88%, respectively),
      but not for adult men (28%). Participants felt that adolescents were the most
      appropriate subjects for HIV preventive vaccine trials (93.7%) but also thought
      that HIV-positive persons were eligible for trials (60.2%), and only 20% thought
      a preventive vaccine could help control HIV. HIV vaccine awareness increased from
      68% at baseline to 81% at follow-up (P<0.001). Willingness to participate in HIV
      preventive vaccine trials was 77%. Vaccine knowledge and willingness to
      participate in trials are high in this population. However, there still is need
      for education on the potential role of preventive HIV vaccines in the control of
      the epidemic and the importance of vaccination for men, especially in the context
      of an HIV vaccine.

PMID- 15167292
TI  - Challenges to conducting HIV preventative vaccine trials with adolescents.
AB  - It is estimated that 10.3 million people aged 15-24 are living with HIV
      infection/AIDS worldwide, with 7000 new infections occurring each day. Many of
      these infections occur during the adolescent years. These rates of infection make
      adolescents an important target for research in primary prevention. Currently,
      preparations are under way by the National Institutes of Health-supported HIV
      networks--the Adolescent Trials Network, the Pediatric AIDS Clinical Trials
      Group, and the HIV Vaccines Trials Network--for phase 1/2 HIV vaccine trials
      involving adolescents in the United States. Identifying the challenges to
      conducting HIV vaccine trials with this population is a crucial component of
      these preparations. Challenges to HIV vaccine trials with adolescents were
      identified by reviewing previous vaccine research for adolescents and HIV
      infection in adolescents and speaking with experts in HIV/AIDS and adolescent
      medicine. Adolescents (typically those younger than 18 years of age) are minors
      and fall under ethical and regulatory safeguards for their participation in
      clinical research including parental permission. Adolescents may not
      appropriately perceive personal risk, posing challenges for informed consent as
      well as prevention counseling during a trial. Safety and immunogenicity studies
      of adolescents are likely to be required by the US Food and Drug Administration
      before vaccine approval for this population. Early identification and subsequent
      follow-up of high-risk adolescents are problematic. Vaccine-induced
      seropositivity may present potential barriers to military service, employment,
      marriage, and acquiring health insurance. The age at optimal immunization,
      particularly for girls in some countries, may be during preadolescence. The
      successful completion of HIV vaccine trials with adolescents must address these
      challenges both in the United States and internationally. This report addresses
      relevant background information, identifies the issues surrounding HIV vaccine
      trials with adolescents, discusses what progress has been made, and addresses
      plans and implications for the implementation of these trials.

PMID- 15167293
TI  - Importance of sex partner HIV status in HIV risk assessment among men who have
      sex with men.
AB  - Clinical HIV risk assessments have not typically integrated questions about sex
      partners' HIV status with questions about condom use and type of sex. Since 2001,
      we have asked all men who have sex with men (MSM) evaluated in an urban sexually
      transmitted disease (STD) clinic how often in the preceding 12 months they used
      condoms for anal sex with partners who were HIV-positive, HIV-negative, and of
      unknown HIV status. Overall, MSM displayed a pattern of assortative mixing by HIV
      status, particularly for unprotected anal intercourse (UAI). Nevertheless, 433
      (27%) of 1580 MSM who denied knowing they were HIV-positive and 93 (43%) of 217
      HIV-positive MSM reported having UAI with a partner of opposite or unknown HIV
      status. Among men who denied previously knowing they were HIV-positive, 24 (9.6%)
      of 251 MSM who reported having UAI with an HIV-positive partner or partner of
      unknown HIV status compared with 11 (1.7%) of 620 MSM who denied such exposure
      tested HIV-positive (odds ratio=5.8, 95% confidence interval: 2.8-12.1). UAI with
      an HIV-positive partner or partner with unknown HIV status was 69% sensitive and
      73% specific in identifying men with previously undiagnosed HIV infection; UAI
      regardless of partner HIV status was 80% sensitive but only 45% specific. The
      positive predictive value was highest for risk assessments that included partner
      HIV status. Integrating questions about anal sex partner HIV status and condom
      use identifies MSM at greatest risk for HIV acquisition and transmission. These
      risk criteria might be effectively used to triage MSM into more intensive
      prevention interventions.

PMID- 15167294
TI  - The future face of coinfection: prevalence and incidence of HIV and hepatitis C
      virus coinfection among young injection drug users.
AB  - The purpose of this study was to determine the prevalence and incidence of HIV
      and hepatitis C virus (HCV) coinfection among young (aged 29 years or younger)
      injection drug users (IDUs) and to compare sociodemographic and risk
      characteristics between (HIV/HCV) coinfected, monoinfected, or HIV- and HCV
      negative youth. Data were collected through the Vancouver Injection Drug Users
      Study (VIDUS). To date, more than 1400 IDUs have been enrolled and followed, of
      whom 479 were aged 29 years or younger. Semiannually, participants have completed
      an interviewer-administered questionnaire and have undergone serologic testing
      for HIV and HCV. Univariate and multivariate logistic regression analyses were
      undertaken to investigate predictors of baseline coinfection. Cox regression
      models with time-dependent covariates were used to identify predictors of time to
      secondary infection seroconversion. A Cochran-Armitage trend test was used to
      determine risk associations across 3 categories: no infection, monoinfection, and
      coinfection. Of the 479 young injectors, 78 (16%) were coinfected with HIV and
      HCV at baseline and a further 45 (15%) with follow-up data became coinfected
      during the study period. Baseline coinfection was independently associated with
      being female, being aboriginal, older age, greater number of years injecting, and
      living in the IDU epicenter. Factors independently associated with time to
      secondary infection seroconversion were borrowing needles and greater than once
      daily cocaine injection, and accessing methadone maintenance therapy in the
      previous 6 months was protective. There were clear trends across the 3 categories
      for increasing proportions of female subjects, aboriginal subjects, older age,
      greater number of years injecting, living in the IDU epicenter, and daily cocaine
      use. There were a shocking number of youth living with coinfection, particularly
      female and aboriginal youth. The median number of years injecting for youth
      seroconverting to a secondary infection was 3 years, suggesting that appropriate
      public health interventions should be implemented immediately.

PMID- 15167295
TI  - Inability to access addiction treatment and risk of HIV infection among injection
      drug users.
AB  - It was recently found that 94% of the nearly $500 million allocated annually to
      Canada's illicit drug strategy has been spent on enforcement-based interventions.
      As a result, lack of funds for addiction treatment has meant demand for substance
      abuse treatment among illicit drug users has exceeded availability. This study
      evaluated whether injection drug users (IDUs) who reported being unable to access
      addiction treatment were at elevated risk of HIV infection. A prospective
      analysis was done of factors associated with syringe borrowing by baseline HIV
      negative IDUs among participants enrolled in the Vancouver Injecting Drug Users
      Study (VIDUS). Since serial measures for each individual were available,
      variables potentially associated with syringe borrowing were evaluated using
      generalized estimating equations (GEEs) with logit link for binary outcomes.
      Overall, 1157 HIV-negative IDUs were enrolled into the VIDUS cohort between May
      1996 and May 2002. Unsuccessful attempts to access addiction treatment were
      associated with reporting syringe borrowing during follow-up in both univariate
      (odds ratio 1.72; 95% CI 1.47-2.00; P<0.001) and in multivariate GEE analyses
      (adjusted odds ratio 1.29; 95% CI 1.09-1.53; P=0.003). Inability to access
      addiction treatment was independently associated with syringe borrowing among HIV
      negative IDUs at risk for HIV infection. These findings suggest that the limited
      provision of addiction treatment may result in a major missed opportunity to
      reduce HIV transmission behavior among IDUs and that the expansion of addiction
      treatment services has major potential to reduce the substantial human and fiscal
      costs of HIV infection.

PMID- 15167296
TI  - Immune status and uptake of antiretroviral interventions to prevent mother-to
      child transmission of HIV-1 in Africa.
AB  - The aim of this study performed in Abidjan, Cote d'Ivoire, was to describe the
      distribution of CD4+ T-cell lymphocytes (CD4) in HIV-1-infected (HIV+) pregnant
      women diagnosed during prenatal voluntary counseling and testing and to assess
      whether HIV-related immunodeficiency influenced the acceptance of an
      antiretroviral (ARV) package (zidovudine beginning at 36 weeks of amenorrhea plus
      intrapartum nevirapine) to prevent mother-to-child transmission. Between April
      and June 2002, a CD4 count was systematically performed in all HIV+ women (n=221)
      in 5 antenatal clinics carrying out voluntary counseling and testing. No
      difference in CD4 count was found in HIV+ women who did not return for their test
      result (n=50) and those who were informed of their positive serostatus (n=171)
      (median CD4 count: 389/mm3 vs. 420/mm3; P=0.19). We also found a lack of
      difference in CD4 count in those who accepted ARV (n=72) and those who did not
      but knew their HIV status (n=99) (median CD4 count: 405/mm3 vs. 425/mm3; P=0.47).
      The overall uptake of the intervention (31.9%) appeared to be independent of the
      maternal immune status.

PMID- 15167297
TI  - CD4+ T-cell gain with nonnucleoside or protease inhibitors: convenience may not
      always be the most convenient.

PMID- 15167299
TI  - Prevalence of HIV-1 primary drug resistance in seroconverters of the ICoNA cohort
      over the period 1996-2001.

PMID- 15167300
TI  - Isoflavones and bone health.

PMID- 15167301
TI  - Is progesterone a vasodilator?

PMID- 15167302
TI  - Measuring fractures: give us a break.

PMID- 15167303
TI  - Beneficial effect of soy isoflavones on bone mineral content was modified by
      years since menopause, body weight, and calcium intake: a double-blind,
      randomized, controlled trial.
AB  - OBJECTIVE: Many studies have shown that soy isoflavones have an effect in
      preventing estrogen-related bone loss, but no data reported whether such an
      effect could be influenced by other important factors affecting bone loss. This
      study examines whether the associations between isoflavone supplementation and
      rates of change in bone mineral content (BMC) could be modified by years since
      menopause (YSM), body weight (BW), and dietary calcium intake in postmenopausal
      Chinese women aged 48 to 62 years. DESIGN: A group of 203 eligible women were
      randomly assigned to three treatment groups: placebo (daily dose of 0 mg
      isoflavones + 500 mg calcium, n = 67), mid-dose (40 mg isoflavones + 500 mg
      calcium, n = 68); and high-dose (80 mg isoflavones + 500 mg calcium, n = 68).
      Bone mineral density (BMD) and BMC at the whole body, spine, and hip were
      measured by dual-energy x-ray absorptiometry at baseline and posttreatment after
      1 year. YSM, BW, and dietary calcium intake stratified analyses were performed to
      evaluate whether the associations between isoflavones supplementation and BMC
      change rates were varied with these factors. RESULTS: Both univariate and
      multivariate analyses observed significant favorable effect of isoflavone
      supplementation on rates of change in BMC at the total hip and trochanter among
      later postmenopausal women (> 4 y), in women with lower BW (< or =median, 55.5
      kg), or among women with lower level of calcium intake (< or =median, 1095 mg/d).
      CONCLUSIONS: The independent effect of soy on the maintenance of hip BMC is more
      marked in women in later menopause or those with lower BW or calcium intake.

PMID- 15167304
TI  - Chronic treatment with progesterone but not medroxyprogesterone acetate restores
      the endothelial control of vascular tone in the mesenteric artery of
      ovariectomized rats.
AB  - OBJECTIVE: To examine whether chronic administration of the natural hormone
      progesterone or a synthetic progestogen, medroxyprogesterone acetate, to
      ovariectomized rats affects the endothelial control of arterial tone in the
      isolated mesenteric artery. DESIGN: Sham-operated rats received a daily
      subcutaneous injection of solvent (sesame oil), whereas ovariectomized rats
      received either sesame oil, progesterone (22 mg kg/day), or medroxyprogesterone
      acetate (22 mg kg/day) for 4 weeks, according to their respective group. RESULTS:
      Phenylephrine-induced contractions were significantly increased (about 200% at 10
      microM) by N-nitro-L-arginine, a nitric oxide synthase inhibitor, in intact
      mesenteric arterial rings from the sham-operated but not from the ovariectomized
      group. The progesterone but not the medroxyprogesterone treatment restored the
      potentiating effect of N-nitro-L-arginine on phenylephrine-induced contraction
      (about 180% at 10 microM). Contractions to phenylephrine were not affected by the
      combination of charybdotoxin plus apamin, two inhibitors of endothelium-derived
      hyperpolarizing factor-mediated responses, in all groups. Acetylcholine induced
      endothelium-dependent relaxations, which were partially inhibited by N-nitro-L
      arginine and abolished by the combination of N-nitro-L-arginine plus
      charybdotoxin and apamin, in all groups. Acetylcholine induced similar
      charybdotoxin and apamin-sensitive hyperpolarizations in intact mesenteric artery
      segments from all groups. CONCLUSIONS: Chronic administration of progesterone,
      but not medroxyprogesterone, to ovarictomized rats restores the endothelium
      dependent attenuation of contractile responses to phenylephrine in mesenteric
      arterial rings through the endothelial formation of nitric oxide. Thus, an
      enhancement of the protective effect of endothelial cells on the arterial wall
      might contribute to the beneficial effect of certain progestogen-containing
      preparations during hormonal treatment.

PMID- 15167306
TI  - Effect of raloxifene on quality of life: a prospective study using the Utian
      Quality of Life (UQOL) Scale.
AB  - OBJECTIVE: The Utian Quality of Life Scale (UQOL) is a new questionnaire used to
      quantify patient perception of quality of life in postmenopausal women. The
      current study is the first to use the UQOL in ascertaining treatment effects on
      quality of life in postmenopausal women. DESIGN: This was a randomized, double
      blind, placebo-controlled study of healthy postmenopausal women. Participants
      were randomized to raloxifene 60 mg/day or placebo. Participants completed the
      UQOL at baseline, at 3 months, and at the 6-month study endpoint. RESULTS: A
      total of 74 women (mean age, 55.6 years) were randomized. In the overall
      population, there were no significant changes from baseline to 6 months within or
      between treatment groups in any of the domains or total score, although
      raloxifene was associated with positive changes from baseline in the occupational
      (P = 0.093) and health (P = 0.055) domains. In women who completed the study,
      raloxifene was associated with a significant improvement from baseline in the
      occupational (P = 0.041) and health (P = 0.025) domains and in the total score (P
      = 0.044), whereas placebo had no effect. There were no statistically significant
      differences between raloxifene and placebo in any of the domains or total score.
      CONCLUSION: Although there were no treatment group differences, raloxifene was
      associated with an improvement from baseline in the occupational and health
      domains and in the overall score of the UQOL. Larger studies are needed using the
      UQOL as a primary endpoint to determine whether the positive effects of
      raloxifene on quality of life observed in this trial are real or a chance
      finding.

PMID- 15167305
TI  - Validity of self-report for fractures among a multiethnic cohort of
      postmenopausal women: results from the Women's Health Initiative observational
      study and clinical trials.
AB  - OBJECTIVE: The purpose of this study is to examine the validity of, and factors
      associated with, the accuracy of self-report (participant-report and proxy
      report) for fractures. DESIGN: Study participants were from the Women's Health
      Initiative Clinical Trial and Observational Study cohorts. All women were
      postmenopausal; populations included American Indian, Asian/Pacific Islander,
      black, Hispanic, and non-Hispanic white. The average length of follow-up was 4.3
      years. Self-reported fractures were adjudicated by reviewing medical records. The
      first adjudicated self-report of fractures for each participant was included in
      the analysis (n = 6,652). RESULTS: We found substantial variations in validity of
      self-report by the fracture site. Agreements between self-reports for single-site
      fractures and medical records were high for hip (78%) and forearm/wrist (81%) but
      relatively lower for clinical spine fractures (51%). The average confirmation
      rate for all single-site fractures was 71%. Misidentification of fracture sites
      by participants or proxy-reporters seemed to be a cause of unconfirmed self
      reports. Higher confirmation rates were observed in participant-reports than in
      proxy-reports. Results of the multivariate analysis indicated that multiple
      factors, such as ethnicity, a history of osteoporosis or fractures, body mass
      index, years since menopause, smoking status, and number of falls in the past
      year were significantly (P < 0.05) related to the validity of self-report.
      CONCLUSION: The validity of self-reports for fracture varies by fracture sites
      and many other factors. The assessed validity in this study is likely
      conservative because some of the unconfirmed self-reports may be due to poor
      medical record systems. The validity of self-reports for hip and forearm/wrist
      fractures is high in this study, supporting their use in epidemiological studies
      among postmenopausal women.

PMID- 15167307
TI  - Influence of marketed herbal menopause preparations on MCF-7 cell proliferation.
AB  - OBJECTIVE: Given the increasing use of alternative menopause treatments, we
      evaluated the effect of several herbal preparations used for menopause relief on
      the proliferation of estrogen-sensitive breast cancer cells (MCF-7) as a means of
      assessing appropriateness for use in women at risk for estrogen-sensitive breast
      cancer. DESIGN: An MCF-7 cell culture model, as described previously, was used to
      evaluate the estrogen-agonist and -antagonist activity of commercially available
      herbal menopause preparations containing red clover, soy, black cohosh, or a
      combination of herbs. Each test substance was evaluated for cytotoxic effects
      before conducting the proliferation assays. RESULTS: Commercially available
      products containing soy, red clover, and herbal combinations induced an increase
      in the MCF-7 proliferation rates, indicating an estrogen-agonistic activity in
      the absence of estradiol. In contrast, an isopropanolic black cohosh extract
      (Remifemin Menopause) did not stimulate MCF-7 growth and exerted inhibitory
      effects on cellular proliferation. None of the tested products enhanced estradiol
      induced cell proliferation. The black cohosh preparation and one of the herbal
      combinations exhibited strong estrogen-antagonistic effects. CONCLUSIONS: The
      lack of proliferative effects of isopropanolic black cohosh extract on estrogen
      sensitive breast cancer cells in vitro suggests a favorable safety profile for
      use in women with a history of breast cancer. Alternatively, preparations
      containing red clover, soy, and combinations of various herbal ingredients may
      induce cell proliferation, suggesting that such herbal preparations should be
      used with caution in the treatment of menopause symptoms in women at risk for, or
      with a history of, estrogen-sensitive breast cancer.

PMID- 15167308
TI  - The effect of soy protein isolate on bone metabolism.
AB  - OBJECTIVE: This double-blind, 15-month pilot study was designed to investigate
      the effect of soy protein isolate with varying concentrations of isoflavones on
      early postmenopausal bone loss and lipids. DESIGN: A total of 65 women, with a
      mean age of 55 years and 7.5 years since menopause, were randomized to one of
      three groups; soy protein with 96 mg isoflavones/day, soy with 52 mg
      isoflavones/day, or soy without isoflavones (< 4 mg isoflavones/day). Soy was
      given for 9 months and then discontinued; participants were followed for an
      additional 6 months. Bone mineral density (BMD) and blood lipids were measured
      during this time. RESULTS: Measurement of serum isoflavones at 3 months showed
      dose-related increases in the three groups. There was no significant effect of
      the soy supplements on BMD of the spine or femoral neck in any of the three
      groups. BMD increased significantly in the trochanter at 9 months (P = 0.0219)
      and at 15 months (P < 0.05) in the group given isoflavone-free soy compared with
      the other two groups. There was no significant effect of soy on lipid metabolism
      at the end of the intervention. CONCLUSION: The present study did not find a
      significant positive effect of soy protein isolate supplemented with isoflavones
      on BMD and the serum lipid profile in early postmenopausal women.

PMID- 15167309
TI  - The effect of hormone therapy and raloxifene on serum matrix metalloproteinase-2
      and -9 in postmenopausal women.
AB  - OBJECTIVE: The aim of the study was to investigate the effect of continuous
      combined hormone therapy and raloxifene on the total and active forms of serum
      matrix metalloproteinase (MMP) -2 and -9. DESIGN: The study was double-blinded,
      with a placebo run-in period of 28 to 50 days. Twenty-eight women received either
      17beta-estradiol 2 mg + norethisterone acetate 1 mg (E2/NETA) or raloxifene HCL
      60 mg for a period of 6 months. Total and active forms of MMP-2 and -9 were
      estimated at baseline and at month 6. RESULTS: Total MMP-2 increased
      significantly in both E2/NETA and raloxifene groups (raloxifene baseline: 278.1
      +/- 18.1 ng/mL; 6 months: 303.1 +/- 29.9 ng/mL, P = 0.008) (E2/NETA baseline:
      281.9 +/- 27.5 ng/mL; 6 months: 298.8 +/- 12.7 ng/mL, P = 0.025). Similarly, both
      treatments increased the active MMP-2 fraction, although only the raloxifene
      associated increase acquired significance (raloxifene baseline: 24.9 +/- 8.6
      ng/mL; 6 months: 31.6 +/- 15.3 ng/mL, P = 0.045) (E2/NETA baseline: 21.7 +/- 5.7
      ng/mL; 6 months: 27.4 +/- 5.8 ng/mL, P = 0.128). Total as well as active
      fractions of MMP-9 were not significantly affected by either treatment.
      CONCLUSIONS: Both E2/NETA and raloxifene increased the total and active MMP-2
      serum levels. MMP-9 was not significantly affected by either regimen. Larger,
      long-term clinical trials are needed to elucidate the effect of HT and raloxifene
      on MMPs and the possible clinical implications for cardiovascular health.

PMID- 15167310
TI  - Body mass index does not influence response to treatment, nor does body weight
      change with lower doses of conjugated estrogens and medroxyprogesterone acetate
      in early postmenopausal women.
AB  - OBJECTIVE: To determine the effects of lower doses of conjugated estrogens (CE)
      alone or in combination with medroxyprogesterone acetate (MPA) on body weight and
      to evaluate the influence of body mass index (BMI) on the effect of lower-dose CE
      or CE/MPA on vasomotor symptoms, vaginal atrophy, bone mineral density (BMD),
      endometrial safety, and side effects such as endometrial bleeding and breast
      pain. DESIGN: In this large clinical trial [the Women's Health, Osteoporosis,
      Progestin, Estrogen (Women's HOPE) study], 2,673 healthy, postmenopausal women
      with intact uteri were randomized for 1 year of CE 0.625, CE 0.625/MPA 2.5, CE
      0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5, CE 0.3, CE 0.3/MPA 1.5 (all doses mg/d),
      or placebo. Weight, BMI, number and severity of hot flushes, vaginal atrophy (as
      determined by the vaginal maturation index), bleeding profiles, breast pain, and
      endometrial biopsies were evaluated. A subset of 822 women was randomized into a
      2-year substudy to evaluate changes in BMD with lower-dose CE or CE/MPA regimens.
      RESULTS: After 1 year of treatment, a small but significant (P < 0.05) gain in
      body weight from baseline was observed in all arms of the study, the largest
      increase in body weight occurring in the placebo group [1.15 +/- 0.21 (SE) kg].
      Body mass index had no significant effect on changes from baseline for vasomotor
      symptoms, bleeding patterns, vaginal atrophy, BMD, endometrial safety, or breast
      pain when analyzed both by analysis of covariance with baseline BMI as covariate
      or when participants were grouped into BMI less than 25 kg/m and BMI of 25 kg/m
      or greater. In placebo-treated women, vaginal atrophy was significantly greater
      (P < 0.05) in women with a BMI less than 25 kg/m compared with a BMI of 25 kg/m
      or greater. CONCLUSIONS: Lower- and standard-dose regimens of CE or CE/MPA are
      not associated with greater weight gain than placebo. In addition, BMI does not
      seem to influence effects of these regimens on vasomotor symptoms, vaginal
      atrophy, bleeding profiles, BMD, endometrial safety, or breast pain.

PMID- 15167311
TI  - Association between hormonal changes at menopause and the risk of a coronary
      event: a longitudinal study.
AB  - OBJECTIVE: To investigate the association of hormone levels at menopause,
      lifestyle variables, and body composition with the predicted 10-year risk of a
      coronary event, calculated using the PROCAM scoring system, in a population-based
      sample of Australian-born, middle-aged women. DESIGN: A 9-year prospective study
      of 438 Australian-born women, who at baseline were aged 45 to 55 years and had
      menstruated in the prior 3 months. Interviews, fasting blood, and physical
      measurements were taken annually. The risk of an acute coronary event was
      calculated using the PROCAM scoring system (includes: age, low-density
      lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic
      blood pressure, family history of premature myocardial infarction, diabetes
      mellitus, and triglycerides). RESULTS: Retention rate after 8 years of follow-up
      was 88% (n = 387). In women not using hormone therapy (HT): higher than average
      body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than
      average estradiol levels (P < 0.005), estradiol levels that decreased (P <
      0.001), and high free testosterone levels (P < 0.05) were associated with
      increased risk of a coronary event. There was a trend for high exercise frequency
      to be associated with a decreased risk (P < 0.07). After BMI and lifestyle
      variables were taken into account, use of HT did not have a significant effect on
      risk of a coronary event. CONCLUSION: In this longitudinal observational study of
      middle-aged Australian-born women, high BMI, an increase in BMI, high free
      testosterone, low estradiol, and a decrease in estradiol levels were the main
      determinants of increased risk of an acute coronary event, based on the PROCAM
      scoring system calculation. More frequent exercise tended to lower the risk.

PMID- 15167312
TI  - Association of cardiovascular risk factors with intima-media thickness of the
      carotid arteries in early postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to examine the association between carotid
      intima-media thickness (IMT) and coronary heart diseases (CHD) risk factors in a
      large population of peri- and postmenopausal women. DESIGN: Participants in this
      study were 906 healthy peri- and postmenopausal women from southwestern France,
      45 to 65 years old with no history of cardiovascular disease and no utilization
      of estrogen/hormone therapy. Women were classified either as perimenopausal (n =
      240) or post-menopausal (n = 666) according both to the regularity of menses and
      to serum follicle-stimulating hormone and estradiol values. All women answered a
      questionnaire, which included 72 questions, related to the identification of
      familial and personal cardiovascular risk factors. Biological measurements were
      performed to evaluate their lipid-lipoprotein profiles and fasting glucose
      levels, ultrasonography was used to measure IMT and total body scanners by DXA
      were performed to determine the percentage of body fat. RESULTS: Multiple
      regression analyses were used to examine the ability of each variable to explain
      IMT values. Mean IMT of the right carotid artery was 0.520 (+/- 0.07) mm. Of the
      906 women, 9% were currently taking lipid-lowering drugs, 12.8% and less than 2%
      were being treated for hypertension and diabetes, respectively. Additionally, 124
      women were found to have current hypertension, 10% had a familial history of CHD,
      and 18% were regular smokers. In multiple regression analyses, only increasing
      age (P < 0.001) and systolic and diastolic blood pressure (P < 0.001) were
      independently and significantly associated with IMT. CONCLUSIONS: These results
      show that only a few risk factors were associated with IMT in this population of
      healthy peri- and postmenopausal women. These results might be related to the
      fact that this study was conducted in an area of France well known for having the
      lowest rates of CHD in women, which is further supported by the thinner IMT found
      in this population as compared with a higher-risk population. Therefore, these
      results might not be relevant for CHD in older or high-risk women.

PMID- 15167313
TI  - Substitution of transdermal estradiol during oral estrogen-progestin therapy in
      postmenopausal women: effects on hypertriglyceridemia.
AB  - OBJECTIVE: We investigated effects of changing from oral estrogen to transdermal
      estradiol on the lipid and lipoprotein profile of postmenopausal women who
      developed hypertriglyceridemia (serum concentrations exceeding 150 mg/dL) during
      estrogen-progestin therapy. DESIGN: Sixty-one postmenopausal Japanese women
      receiving 0.625 mg of conjugated equine estrogen plus 2.5 mg of
      medroxyprogesterone acetate daily for 12 months had developed serum triglyceride
      concentrations exceeding 150 mg/dL after 12 months of treatment. Thirty-six of
      them, chosen randomly for study, were assigned at random to either a group that
      continued this oral regimen or another that changed to transdermal estradiol
      while continuing 2.5 mg of oral medroxyprogesterone acetate for the next 3 months
      (n = 18 for each). Blood lipids were compared between groups. RESULTS: Serum
      concentrations of triglyceride and very-low-density lipoprotein triglyceride
      decreased significantly after changing to transdermal estradiol (triglyceride,
      from 226.0 +/- 43.9 to 110.5 +/- 44.1 mg/dL, P < 0.01). No changes were seen in
      concentrations of low-density lipoprotein cholesterol or high-density lipoprotein
      cholesterol. CONCLUSION: Changing to transdermal estradiol may improve
      triglyceride metabolism in women who developed hypertriglyceridemia during oral
      estrogen-progestin therapy, with minimal effect on cholesterol profiles.

PMID- 15167314
TI  - Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents
      bone loss in osteopenic postmenopausal women.
AB  - OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg
      17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal
      osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with
      osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of
      the premenopausal mean value] were enrolled in a 2-year prospective, randomized
      study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg
      trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All
      received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD
      measurements at the lumbar spine, total hip, and femoral neck as well as blood
      and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone
      specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place
      regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8%
      at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001).
      The biochemical markers of bone turnover were suppressed accordingly. Serum
      CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively,
      whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a
      more retarded decrease of 40% and 33%, respectively. Of the women receiving
      hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew
      prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen +
      progestogen therapy is efficient in increasing BMD in an osteopenic
      postmenopausal population. Furthermore, it is well tolerated, with few adverse
      events and an early bleeding control, which is likely to improve compliance to
      the treatment over the long term.

PMID- 15167315
TI  - A cost-effectiveness evaluation of two continuous-combined hormone therapies for
      the management of moderate-to-severe vasomotor symptoms.
AB  - OBJECTIVES: After the release of the results of the Women's Health Initiative, an
      emerging consensus suggests that continuous-combined hormone therapy (CCHT)
      should be limited to short-term management of moderate-to-severe vasomotor
      symptoms. This, in turn, raises the important question of the economic value, if
      any, of short-term CCHT for this indication. We conducted a cost-effectiveness
      analysis comparing a 1-year treatment course with 1 mg of norethindrone acetate/5
      microg of ethinyl estradiol (1/5 NA/EE) or 0.625 mg/day of conjugated estrogens
      plus 2.5 mg of medroxyprogesterone (0.625/2.5 CEE/MPA) compared with no therapy
      for the management of moderate-to-severe vasomotor symptoms. DESIGN: A literature
      based Markov model was developed to compare these three options' cost and quality
      of-life (QOL) benefits. The impact of therapy on vasomotor symptoms and
      breakthrough bleeding/spotting on the direct costs of care and QOL were
      considered. RESULTS: Compared with no therapy, CCHTs resulted in net increases in
      quality-adjusted life-years (QALYs) gained (0.110 for 1/5 NA/NE v 0.104 for
      0.625/2.5 CEE/MPA). Net costs (v no therapy) were $167 lower for 1/5 NA/NE
      compared with 0.625/2.5 CEE/MPA. Cost per QALY gained (compared with no therapy)
      were $6,200 and $8,200, respectively. Cost-effectiveness was most favorable for
      individuals with more severe symptoms who were less bothered by breakthrough
      bleeding/spotting. CONCLUSIONS: A short-term course of CCHT for the sole purpose
      of managing moderate-to-severe vasomotor symptoms is cost-effective. However, 1/5
      NA/NE seemed to be more cost-effective than 0.625/2.5 CEE/MPA. These findings can
      be used to further refine the role of CCHT and to improve formulary decisions.

PMID- 15167316
TI  - Bioidentical hormone therapy: a review.
AB  - OBJECTIVE: The terms "natural" or "bioidentical" hormone therapy (NHT) are used
      to describe hormone treatment with individually compounded recipes of certain
      steroids in various dosage forms, including dehydroepiandrosterone, pregnenolone,
      testosterone, progesterone, estrone, estradiol, and estriol. Based on the results
      of a person's salivary hormone levels, the final composition of the compounded
      dosage form is individualized to that specific person. Proponents claim that NHT
      is better tolerated than manufactured products. This paper is intended to review
      the concept of NHT and to determine whether there is sufficient scientific
      evidence to support its use. DESIGN: A literature search was performed in Medline
      using the following MeSH terms and key words: drug combinations; progestational
      hormones; hormone replacement therapy; endometrium; estrogen replacement therapy;
      climacteric; menopause; estradiol; estrogens; progesterone; drug monitoring; and
      drug compounding. Current Contents, International Pharmaceutical Abstracts,
      Cochrane Database of Systematic Reviews, Lexis Nexis, Google, Medscape, MD
      Consult, and clinicaltrials.gov were searched with key words. RESULTS: There are
      a few observational studies and clinical trials comparing conventional hormone
      therapy with bioidentical hormone therapy. Studies generally lacked adequate
      study design, including small sample sizes and comparison of inequivalent doses,
      to prove safety and efficacy. Little evidence was found to support individualized
      hormone dosing based upon saliva hormone concentrations. CONCLUSION: Evidence
      suggests that, although individualized hormonal products may decrease some
      symptoms of menopause, it seems they have no proven advantage over conventional
      hormone therapies and their use is not supported by evidence regarding
      pharmacokinetics, safety, and efficacy.

PMID- 15167317
TI  - Depression: 20 years of progress.

PMID- 15167318
TI  - Arthritis and heart disease as risk factors for major depression: the role of
      functional limitation.
AB  - BACKGROUND: Major depression in later life is highest among people with chronic
      illness. Identifying amenable factors that mediate the relationship between known
      risk factors such as arthritis and heart disease with major depression is
      important to the design of clinical and public health strategies to reduce
      depression and its consequences. OBJECTIVE: This study investigates factors
      amenable to clinical and public health intervention that could mediate the
      relationship between chronic illness and major depression. DESIGN: Population
      based national sample. SETTING: United States preretirement age (54-65) adults.
      PARTICIPANTS: A total of 7825 participants from the 1996 Health and Retirement
      Survey. MEASUREMENT: The outcome is major depression based on standardized
      assessment. Independent variables include sociodemographics chronic illness
      profile, functional limitation, health and medical access. RESULTS: A substantial
      burden of major depression is related to chronic illness, particularly arthritis
      (attributable risk [AR], 18.1%; 95% confidence interval [CI], 9.9-25.6) and heart
      disease (AR, 17.6%; 95% CI, 13.4-21.7). Functional limitation is the strongest
      investigated factor associated with depression (AR, 34.4%; 95% CI, 24.8-42.7) and
      attenuates the associations of arthritis and heart disease with depression.
      CONCLUSION: Functional limitation mediates the association of arthritis and heart
      disease with major depression. This relationship offers potential clinical and
      public health strategies to reduce major depression in older adults through
      intervention and management of functional limitation. Alternatively, it might be
      possible to reduce functional loss through screening for depression, particularly
      among people with functional limitation, and effective mental health treatment.
      The importance for clinical management of depression, comorbidity, and functional
      limitation spectrum supports the value of systems-based medicine.

PMID- 15167320
TI  - Monitoring depression care: in search of an accurate quality indicator.
AB  - BACKGROUND: Linking process and outcomes is critical to accurately estimating
      healthcare quality and quantifying its benefits. OBJECTIVES: The objective of
      this study was to explore the relationship of guideline-based depression process
      measures with subsequent overall and psychiatric hospitalizations. RESEARCH
      DESIGN: This is a retrospective cohort study during which we used administrative
      and centralized pharmacy records for sample identification, derivation of
      guideline-based process measures (antidepressant dosage and duration adequacy),
      and subsequent hospitalization ascertainment. Depression care was measured from
      June 1, 1999, through August 31, 1999. We used multivariable regression to
      evaluate the link between depression care and subsequent overall and psychiatric
      hospitalization, adjusting for patient age, race, sex, socioeconomic status,
      comorbid illness, and hospitalization in the prior 12 months. SUBJECTS: We
      studied a total of 12,678 patients from 14 Northeastern VHA hospitals. RESULTS:
      We identified adequate antidepressant dosage in 90% and adequate duration in 45%.
      Those with adequate duration of antidepressants were less likely to be
      hospitalized in the subsequent 12 months than those with inadequate duration
      (odds ratio [OR],.90; 95% confidence interval [CI], .81-1.00). Those with
      adequate duration of antidepressants were less likely to have a psychiatric
      hospitalization in the subsequent 12 months than those with inadequate duration
      (OR, .82; 95% CI, .69-.96). We did not demonstrate a significant link between
      dosage adequacy and subsequent overall or psychiatric hospitalization.
      CONCLUSIONS: Guideline-based depression process measures derived from centralized
      data sources offer an important method of depression care surveillance. Their
      accuracy in capturing depression care quality is supported by their link to
      healthcare utilization. Further work is needed to assess the effect of
      implementing these quality indicators on depression care.

PMID- 15167319
TI  - Chronic medical illness, depression, and use of acute medical services among
      Medicare beneficiaries.
AB  - BACKGROUND: This study assessed the relation of comorbid depressive syndrome with
      utilization of emergency department services and preventable inpatient
      hospitalizations among elderly individuals with chronic medical conditions.
      RESEARCH DESIGN: A cross-sectional study. SETTING: Individuals greater than or
      equal to 65 years of age living in the United States with Medicare part A and B
      fee-for-service coverage in 1999. SUBJECTS: A 5% random sample of elderly
      Medicare recipients (N = 1,238,895) of whom 60,382 (4.9%) met criteria for a
      depressive syndrome. MEASUREMENTS: Medicare beneficiaries were stratified based
      on the presence of at least 1 of the following medical conditions: coronary
      artery disease, diabetes mellitus, congestive heart failure, hypertension,
      prostate cancer, breast cancer, lung cancer, or colon cancer. For each stratum,
      we compared the odds of emergency department visits, all-cause hospitalization,
      and hospitalization for ambulatory care sensitive conditions (ACSC), conditions
      for which timely and effective medical care could decrease risk of
      hospitalization, for beneficiaries with and without a depressive syndrome.
      RESULTS: Compared with those without a depressive syndrome, beneficiaries with a
      depressive syndrome were more likely to be older, white, and female (P <0.001).
      For each of the 8 chronic medical conditions, elderly beneficiaries with a
      depressive syndrome were at least twice as likely to use emergency department
      services (range of adjusted odds ratios, 2.12-3.16; P <0.001); medical inpatient
      hospital services (range of adjusted odds ratios, 2.59-3.71; P <0.001); and
      medical inpatient hospital services associated with an ACSC (range of adjusted
      odds ratios, 1.72-2.68; P <0.001) as compared with those without a depressive
      syndrome. CONCLUSIONS: For elderly individuals with at least 1 chronic medical
      condition, the presence of a depressive syndrome increased the odds of acute
      medical service use, suggesting that improvements in clinical management, access
      to mental health services, and coordination of medical and mental health services
      could reduce utilization.

PMID- 15167322
TI  - A longitudinal population-based study of treated and untreated major depression.
AB  - BACKGROUND: Few studies have investigated the factors associated with different
      outcomes in individuals with major depressive episode (MDE) in relation to mental
      health service utilization. OBJECTIVES: This study was to, in depressed
      individuals who used and did not use mental health services, 1) compare the
      demographic, psychosocial, and clinical characteristics; 2) estimate the risk of
      MDE in a 6-year follow-up period; and 3) identify the factors associated with the
      persistence/recurrence of MDE. DESIGN: This was a population- based longitudinal
      analysis. SUBJECTS: Participants included the longitudinal cohort of the Canadian
      National Population Health Survey who reported MDE at the baseline survey (n =
      609). MEASURES: MDE was measured by the Composite International Diagnostic
      Interview-Short Form for Major Depression. RESULTS: In the 6-year follow-up
      period, 49.8% of participants with treated depression developed subsequent MDE;
      28.7% of those with untreated depression reported MDE. Multivariate analyses
      showed that, among those who reported the use of mental health services,
      childhood and adulthood traumatic events and functional impairment were related
      to the recurrence of MDE. Among those who did not use mental health services,
      reported negative life events and the severity of depressive symptoms were
      predictive of recurrent MDE. CONCLUSIONS: The risk of the recurrence of MDE and
      associated factors differ in mental health service users and nonusers. Future
      studies need to confirm these results and to identify service barriers for those
      who do not use the services and who are at a high risk of MDE.

PMID- 15167321
TI  - Measuring quality of pharmacotherapy for depression in a national health care
      system.
AB  - OBJECTIVES: This article examines the use of antidepressant medication in the
      treatment of major depression in the Department of Veterans Affairs (VA) during
      the 2001 fiscal year and considers the relationship of patient, drug, provider,
      and facility to adherence to medication treatment guidelines. METHODS:
      Prescription drug records for all VA outpatients diagnosed with major depression
      (International Classification of Diseases, 9th edition, code 296.2 or 296.3) were
      collected for October 2000 through September 2001. Indicators were constructed
      that noted whether patients newly treated with antidepressants (i.e., with no
      prescription in the previous 8 weeks) received at least 180 days (continuation
      phase) of antidepressant drug treatment (84- and 140-day measures were also
      considered). Logistic regression with and without center fixed effects and
      generalized estimation equations were used to identify patient, drug, and
      facility characteristics that were associated with these treatment quality
      indicators. RESULTS: Of the 27,713 patients in the final sample, 54% received at
      least 181 days of treatment. This is higher than recent rates reported by Health
      Employer Data and Information Set (HEDIS) for the general population, although
      our measures and those used by HEDIS are not exactly the same. Women, married
      patients, older patients, and whites were more likely than others to have higher
      quality antidepressant drug treatment. Contrary to previous research, we find few
      significant differences among specific antidepressant agents prescribed in this
      large sample. Comorbid substance abuse was associated with fewer days of
      treatment, whereas other psychiatric comorbidities increased the length of
      treatment. We found few differences resulting from provider type. Although
      significant differences among facilities were found in the unadjusted rates
      (similar to those used by HEDIS), these diminished greatly after controlling for
      relevant covariates. CONCLUSIONS: In the nation's largest mental health system,
      quality of pharmacotherapy for depression, at least by one standard measure, is
      relatively good. We found the specific antidepressant drug used has little impact
      on quality. In considering differences among facilities, we found that it is
      critical to control for relevant patient characteristics.

PMID- 15167323
TI  - Use of antidepressant medications: are there differences in psychiatric visits
      among patient treatments in the Veterans Administration?
AB  - BACKGROUND: Information on the effectiveness of newer antidepressants like
      serotonin-norepinephrine reuptake inhibitors in terms of healthcare utilization
      is limited. Treatment guidelines affect evaluation. Second-line medications are
      usually prescribed to patients with higher utilization. OBJECTIVES: The objective
      of this study was to compare antidepressants within the Veterans Affairs (VA)
      healthcare system on the basis of the number of outpatient psychiatric visits for
      each class of antidepressants. RESEARCH DESIGN AND SUBJECTS: We conducted a
      retrospective cohort design using precollected information from VA national
      databases from 1999 and 2000. The study identified 92,537 patients on serotonin
      specific reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake
      inhibitors (SNRIs), or tricyclic antidepressants (TCAs). MEASURES: We stratified
      individual patients by the number of visits in the baseline year for each
      medication class. For each stratum, we created a dichotomized variable YK: Yk = 1
      if there is a reduction of K visits or more and 0 if there is no reduction. We
      calculated the odds of reduction of psychiatric visits among the 3 classes of
      antidepressants. RESULTS: TCAs and SSRIs were associated with greater odds of
      reduction compared with SNRIs at the level of 1 through 10 or 11 visits,
      respectively. SNRIs were associated with greater odds of reduction in visits at
      the level of 14, 16, or more visits compared with SSRIs and TCAs, respectively (P
      <0.05). SSRIs were associated with greater odds of reduction compared with TCAs
      at the level of 1 to 11 visits (P <0.05); there were no significant differences
      between the 2 classes above 11 visits. CONCLUSION: Effectiveness research using
      databases should consider how medications are prescribed within systems.
      Treatment guidelines result in differences in severity and utilization among
      users of different medications.

PMID- 15167324
TI  - Outcomes of states' scholarship, loan repayment, and related programs for
      physicians.
AB  - CONTEXT: Many states attempt to entice young generalist physicians into rural and
      medically underserved areas with financial support-for-service programs
      scholarships, service-option loans, loan repayment, direct financial incentives,
      and resident support programs-with little documentation of their effectiveness.
      OBJECTIVE: The objective of this study was to assess outcomes of states' support
      for-service programs as a group and to compare outcomes of the 5 program types.
      DESIGN: We conducted a cross-sectional, primarily descriptive study.
      PARTICIPANTS: We studied all 69 state programs operating in 1996 that provided
      financial support to medical students, residents, and practicing physicians in
      exchange for a period of service in underserved areas; federally funded
      initiatives were excluded. We also surveyed 434 generalist physicians who served
      in 29 of these state programs and a matched comparison group of 723 nonobligated
      young generalist physicians. DATA COLLECTION: Information on eligible programs
      was collected by telephone, mail questionnaires, and from secondary sources.
      Obligated and nonobligated physicians were surveyed, with 80.3% and 72.8%
      response rates, respectively. MAIN OUTCOME MEASURES: Levels of socioeconomic need
      of communities and patients served by physicians, programs' participant service
      completion and retention rates, and physicians' satisfaction levels. RESULTS:
      Compared with young nonobligated generalists, physicians serving obligations to
      state programs practiced in demonstrably needier areas and cared for more
      patients insured under Medicaid and uninsured (48.5% vs. 28.5%, P <0.001).
      Service completion rates were uniformly high for loan repayment, direct
      incentive, and resident-support programs (93% combined) but lower for student
      targeting service-option loan (mean, 44.7%) and scholarship (mean, 66.5%)
      programs. State-obligated physicians were more satisfied than nonobligated
      physicians, and 9 of 10 indicated that they would enroll in their programs again.
      Obligated physicians also remained longer in their practices than nonobligated
      physicians (P = 0.03), with respective group retention rates of 71% versus 61% at
      4 years and 55% versus 52% at 8 years. Retention rates were highest for loan
      repayment, direct incentive, and loan programs. CONCLUSIONS: States' support-for
      service programs bring physicians to needy communities where a strong majority
      work happily and with at-risk patient populations; half stay over 8 years. Loan
      repayment and direct financial incentive programs demonstrate the broadest
      successes.

PMID- 15167325
TI  - Estimating health-related quality of life in populations through cross-sectional
      surveys.
AB  - BACKGROUND: Health-related quality of life (HRQL) is optimally reported from the
      individual vantage point; consequently, prevalence estimates from the National
      Health Interview Survey (NHIS) could be misleading, because approximately one
      third of the information is proxy-provided. OBJECTIVE: The objective of this
      study was to discern the degree to which disparities in the crude prevalence of
      reduced HRQL is explainable by case-mix differences between proxy- and self
      reportees. SUBJECTS: We studied the cross-sectional data on 96,091 persons from
      the 1994-1995 NHIS Supplement on Disability. RESEARCH DESIGN: We conducted a
      study of reduced HRQL expressed as a respondent type indicator (proxy vs. self)
      adjusting for socioeconomic differences and limitations in function. MEASURES: We
      studied reduced HRQL indicated by 1) perception of poor health, 2) perception of
      disability, 3) 30 or more bed days in the last year, or 4) 20 or more doctor
      visits in the last year. RESULTS: The crude estimated prevalence of reduced HRQL
      for proxy reports was approximately half that of self-reports. Although the
      unadjusted odds ratios (ORs) for proxy- compared with self-reportees ranged from
      0.51 (95% confidence interval [CI], 0.47-0.55) to 0.59 (95% CI, 0.55-0.64), case
      mix adjustment resulted in a significant directional change for poor health
      perception, and all adjusted ORs were substantially closer to 1.0 than their
      unadjusted counterparts. CONCLUSION: Adjustment for case-mix explained away most
      of the proxy-/self-report disparity, suggesting that a major component of
      differences in prevalence between proxy- and self-respondents is case-mix
      related. Consequently, compared with excluding proxy reports, inclusion of proxy
      reports results in relatively less bias when the NHIS-D is applied to obtain
      prevalence estimates for the indicators studied.

PMID- 15167327
TI  - Hospital-level performance improvement: beta-blocker use after acute myocardial
      infarction.
AB  - BACKGROUND: National surveys indicate improvement in beta-blocker use after acute
      myocardial infarction (AMI) over time; however, these data could obscure
      important variation in improvement at individual hospitals. Our objective was to
      characterize the hospital-level variation in the improvements in beta-blocker
      prescription rates after AMI and to identify hospital characteristics that were
      associated with hospital improvement rates after adjustment for patient
      demographic and clinical characteristics. METHODS AND RESULTS: We used data (n =
      335,244 patients with AMI discharged from 682 hospitals) from the National
      Registry of Myocardial Infarction (NRMI) and from the American Hospital
      Association Annual Survey of Hospitals and hierarchical modeling to examine the
      associations between hospital characteristics and hospital-level rates of change
      in beta-blocker use during 1996-1999. On average, hospital rates of beta-blocker
      use for patients with AMI increased 5.9 percentage points (standard deviation,
      9.7 percentage points) from the premidpoint time period (April 1996-February
      1998) to the postmidpoint time period (March 1998-September 1999) of the study.
      The range in hospital-level changes in beta-blocker rates was substantial, from a
      decline of -50.0 percentage points to an increase of +35.7 percentage points. AMI
      volume and teaching status, geographic region, and initial beta-blocker use rates
      were associated with rate of improvement, but the magnitude of these effects was
      modest. CONCLUSIONS: The study reveals marked hospital-level variation in
      improvement in beta-blocker use after AMI. Several hospital characteristics were
      associated with this improvement, but they are weak predictors of hospital-based
      improvement in the use of beta-blockers.

PMID- 15167326
TI  - Patient satisfaction with primary care: does type of practitioner matter?
AB  - OBJECTIVE: The objective of this study was to evaluate the association of patient
      satisfaction with type of practitioner attending visits in the primary care
      practice of a managed care organization (MCO). STUDY DESIGN: We conducted a
      retrospective observational study of 41,209 patient satisfaction surveys randomly
      sampled from visits provided by the pediatrics and adult medicine departments
      from 1997 to 2000. Logistic regression, with practitioner and practice fixed
      effects, of patient satisfaction versus dissatisfaction was estimated for each of
      3 scales: practitioner interaction, care access, and overall experience. Models
      were estimated separately by department. Independent variables were type of
      practitioner attending the visit and other patient and visit characteristics.
      RESULTS: Adjusted for patient and visit characteristics, patients were
      significantly more likely to be satisfied with practitioner interaction on visits
      attended by physician assistant/nurse practitioners (PA/NPs) than visits attended
      by MDs in both the adult medicine and pediatrics practices. Patient satisfaction
      with care access or overall experience did not significantly differ by
      practitioner type. In adult medicine, patients were more satisfied on diabetes
      visits provided by MDs than by PA/NPs. Otherwise, patient satisfaction for the
      combined effects of practitioner type and specific presenting condition did not
      differ. CONCLUSIONS: Averaged over many primary care visits provided by many
      physicians and midlevel practitioners, patients in this MCO were as satisfied
      with care provided by PA/NPs as with care provided by MDs.

PMID- 15167328
TI  - Effectiveness and efficiency of opportunistic cervical cancer screening:
      comparison with organized screening.
AB  - BACKGROUND: Several countries have adopted nationally organized cervical
      screening programs, but many continue with opportunistic screening. Comparison of
      the effectiveness and efficiency of the 2 systems is important for informing
      policy. OBJECTIVES: The objectives of this study were to assess the effectiveness
      and efficiency of an opportunistic cervical screening system, and to compare this
      with what could be achieved through an organized program. RESEARCH DESIGN: We
      propose a model for estimating the effectiveness and efficiency of opportunistic
      screening systems and demonstrate it using data from a cross-sectional study of
      1826 women in Hong Kong. We estimated the coverage and frequency of screening and
      used this to estimate effectiveness (number of cases of invasive cervical cancer
      potentially prevented) and efficiency (tests per case prevented) of the current
      system. Similar estimates were made for various organized programs with different
      screening intervals and coverage. RESULTS: Ever screening coverage in this
      opportunistic system was 44%, resulting in 26% to 31% reduction in potential new
      cases (n = 144-183). Compared with this, a 3-yearly or 5-yearly screening policy
      aiming for 80% coverage would prevent an additional 46% (equivalent to 254 new
      cases out of a population of 2.3 million women per year) and 41% (222 per year),
      respectively. This could be achieved with more efficient use of resources,
      reducing the number of tests per case prevented from 2018 to 1545 and 1007,
      respectively. CONCLUSIONS: At best, the effectiveness of this opportunistic
      system is equivalent to an organized program with 10-yearly screening and 50%
      coverage but at much greater cost. Poor coverage and over screening of a minority
      of women contributes to its inefficiency.

PMID- 15167329
TI  - Computerized knowledge management in diabetes care.
AB  - INTRODUCTION: Many scientific achievements become part of usual diabetes care
      only after long delays. The purpose of this article is to identify the impact of
      automated information interventions on diabetes care and patient outcomes and to
      enable this knowledge to be incorporated into diabetes care practice. METHODS: We
      conducted systematic electronic and manual searches and identified reports of
      randomized clinical trials of computer-assisted interventions in diabetes care.
      Studies were grouped into 3 categories: computerized prompting of diabetes care,
      utilization of home glucose records in computer-assisted insulin dose adjustment,
      and computer-assisted diabetes patient education. RESULTS: Among 40 eligible
      studies, glycated hemoglobin and blood glucose levels were significantly improved
      in 7 and 6 trials, respectively. Significantly improved guideline compliance was
      reported in 6 of 8 computerized prompting studies. Three of 4 pocket-sized
      insulin dosage computers reduced hypoglycemic events and insulin doses.
      Metaanalysis of studies using home glucose records in insulin dose adjustment
      documented a mean decrease in glycated hemoglobin of.14 mmol/L (95% confidence
      interval [CI], 0.11-0.16) and a decrease in blood glucose of.33 mmol/L (95% CI,
      0.28-0.39). Several computerized educational programs improved diet and metabolic
      indicators. DISCUSSION: Computerized knowledge management is becoming a vital
      component of quality diabetes care. Prompting follow-up procedures, computerized
      insulin therapy adjustment using home glucose records, remote feedback, and
      counseling have documented benefits in improving diabetes-related outcomes.

PMID- 15167330
TI  - Sacral insufficiency fracture surgically treated by fibular allograft.
AB  - Sacral insufficiency fractures have been known to occur distally after long
      instrumentation to the sacrum. Most such fractures are treated nonoperatively,
      but surgery is indicated for patients who have nonunions, persistent pain,
      neurologic deficits, or gross displacement. The current report elucidates the
      potential complication of sacral fracture after long lumbar arthrodesis, reviews
      the pertinent literature, presents three patients with sacral fractures after
      long instrumented lumbar spinal arthrodesis to the sacrum, and describes a new
      surgical technique for stabilizing such fractures. One patient was treated
      nonoperatively, and two patients were treated with arthrodesis from a posterior
      approach and augmentation with a strut fibular allograft. All three patients were
      followed to radiographic and clinical union. The authors conclude that sacral
      fracture is a potential complication after a long lumbar arthrodesis.
      Nonoperative techniques are often successful, but when they are not, a new
      technique using fibular allografts can be successful.

PMID- 15167331
TI  - Posterior spinal fusion for lumbar degenerative diseases using the Crock
      Yamagishi (C-Y) spinal fixation system.
AB  - Although many transpedicular screw systems have been developed and have undergone
      wide clinical use, experience with semirigid transpedicular systems has rarely
      been reported. We evaluated the efficacy and safety of the Crock-Yamagishi (C-Y)
      system for posterior spinal fusion in lumbar degenerative diseases. The outcomes
      for 26 patients (14 men, 12 women) with lumbar degenerative diseases who
      underwent posterior spinal fusion using the C-Y system were analyzed (posterior
      lumbar interbody fusion (PLIF), 11 patients; posterolateral fusion (PLF), 14; and
      facet fusion (FF), 1. Symptoms were evaluated using the Japanese Orthopaedic
      Association Assessment of Treatment for Low Back Pain (JOA score). Preoperative
      scores ranged from -1 to 23 points (mean, 12.8), while postoperative scores
      ranged from 19 to 29 points (mean, 26.4). Degree of recovery ranged from 23.1% to
      100% (mean, 83.2%). Overall fusion rate was 96.2% (25/26). Neither breakage nor
      loosening of implants was observed radiographically. Intra- and postoperative
      complications included one case of transient L5 nerve root palsy attributable to
      surgical technique, and one deep postoperative infection. The C-Y system,
      categorized as semirigid, is effective when used with one- or two-level PLIF or
      PLF for lumbar degenerative disorders, grade I to II spondylolisthesis, and
      failed back syndrome.

PMID- 15167332
TI  - Postoperative changes of spinal curvature and range of motion in adult patients
      with cervical spinal cord tumors: analysis of 51 cases and review of the
      literature.
AB  - OBJECTIVE: We sought to determine factors likely to influence postoperative
      changes in cervical spinal curvature and range of motion (ROM) in patients with
      cervical spinal cord tumors. METHODS: Fifty-one patients who underwent tumor
      excision via a single posterior approach were examined. Surgical methods were
      classified as follows: group A, expansive open-door laminoplasty (ELAP); group B,
      conventional laminectomy; and group C, hemilaminectomy (HL). Pre- and
      postoperative cervical spinal curvature, cervical curvature type, and ROM were
      evaluated using lateral radiographs. RESULTS: Worsening of cervical curvature
      type was statistically less frequent in group C than in group A or B (P < 0.05),
      although no significant difference was evident overall between pre- and
      postoperative cervical curvature indexes or ROM in any group. Cases of C2 surgery
      showed more frequent curvature worsening (80%) in group A than in other groups (P
      < 0.05). Postoperative changes of the cervical curvature in patients with
      cervical spinal cord tumors were greatly influenced by the surgical method; the
      cervical curvature was particularly unfavorable when patients had C2
      decompression. CONCLUSIONS: Careful attention to postoperative changes in the
      spinal curvature is needed when ELAP is performed, especially if surgery involves
      C2. HL is the best posterior approach for resection of cervical spinal cord
      tumors from the viewpoint of postoperative spinal curvature and ROM.

PMID- 15167333
TI  - Prospective assessment of outcomes improvement following fusion for low back
      pain.
AB  - BACKGROUND: This prospective study was performed to improve the quality of
      outcomes data in patients undergoing spinal fusion for low back pain. There is an
      accepted deficiency of this form of outcomes assessment in the literature. The
      aim was to determine the effectiveness of the surgical procedure in terms of
      patient satisfaction, outcome scores, and third-party measures. METHODS: The
      measures of outcomes assessment included patient satisfaction, pain scores, low
      back outcome and Prolo scores, medication use, and employment status. Data
      collection was prospective prior to and at final follow-up. Eighty percent of 35
      patients were followed for a mean of 31 months. RESULTS: Patient satisfaction was
      71%; however, only 28.6% of patients followed achieved good or excellent low back
      outcome scores. Yet significant improvement occurred: 46.4% achieved a good or
      excellent outcome using the Prolo score. There was a 75% reduction in medication
      usage, and 75% of nonworking compensation patients returned to gainful
      employment. Patient satisfaction was markedly higher than improvement measured by
      the outcome scores. Dramatic improvements in medication usage and return to work
      were achieved, despite less than spectacular outcome scores. CONCLUSIONS: These
      findings support cautious use of posterior spinal fusion. Patients must
      appreciate improvement rather than normality as a realistic aim.

PMID- 15167334
TI  - Case-control study comparing the efficacy of surgical techniques for C1-C2
      arthrodesis.
AB  - Atlantoaxial fusion rates between 85% and 98% using C1-C2 transarticular screw
      (TAS) fixation have been reported; however, all of these studies are class III
      data. As such, these studies carry little or no statistical significance. The
      authors thus designed a case-control study (class II data) to evaluate the
      efficacy of C1-C2 TAS fixation as compared with posterior wiring techniques
      (PWTs). Records of adult subjects were reviewed for fusions isolated to C1-C2.
      Immobilization requirements were a collar for patients treated with TAS fixation
      and a halo for those treated by PWT. The minimum acceptable interval of
      radiographic follow-up was 12 months, and the outcome (fusion or nonunion) was
      determined through independent interpretation by a radiologist. Twenty-seven of
      72 patients undergoing a posterior atlantoaxial arthrodesis met enrollment
      criteria. Sixteen males and 11 females combined for an average age of 54.1 years
      and mean follow-up of 31 months. Successful fusions (n = 18) were defined as
      controls, and cases represented nonunions (n = 9). Successful fusion was achieved
      in 13 of 14 patients treated with the TAS technique as compared with 5 of 13
      subjects who underwent a PWT. Patients with a radiographically solid fusion were
      21 more times likely to have undergone TAS than PWT (P = 0.004). This study
      demonstrated a statistically increased rate of arthrodesis as determined by
      specific radiographic criteria with the use of TAS fixation as compared with PWT.

PMID- 15167335
TI  - Correlative analysis of the results of surgical treatment of thoracolumbar
      injuries with long Texas Scottish rite hospital construct: is the use of pedicle
      screws versus hooks advantageous in the lumbar spine?
AB  - This is a prospective, randomized study to compare the efficacy of two similar
      "long-segment" Texas Scottish Rite Hospital instrumentations with the use of
      hooks in the thoracic spine and pedicle screws versus laminar hook claw in the
      lumbar spine for thoracolumbar A3, B, and C injuries. Forty consecutive patients
      with such thoracolumbar fractures (T11-L1) associated with spinal canal
      encroachment underwent early operative postural reduction and stabilization. The
      patients were randomly sampled into two groups: Twenty patients received hooks in
      "claw configuration" in both the thoracic and the lumbar spine (group A), and 20
      patients received hooks in the thoracic vertebrae and pedicle screws in the
      lumbar vertebrae (group B). Pre- and postoperative plain roentgenograms and
      computed tomography scans were used to evaluate any changes in Gardner post
      traumatic kyphotic deformity, anterior and posterior vertebral body height at the
      fracture level, and spinal canal clearance (SCC). All patients were followed for
      an average period of 52 months (range 42-71 months). The correction of anterior
      vertebral body height was significantly more (P < 0.01) in the spines of group B
      (33%) than in group A (16%), with a subsequent 11% loss of correction at the
      latest evaluation in group A and no loss of correction in group B. There were no
      significant differences in the changes of posterior vertebral body height and
      Gardner angle between the two groups. The SCC was significantly more (P < 0.05)
      immediately postoperatively in the spine of group B (32%) than in group A (19%).
      In the latest evaluation, there was a 9% loss of the immediately postoperatively
      achieved SCC in group A, while SCC was furthermore increased at 10.5% in group B.
      All patients with incomplete neurologic lesions in groups A and B were
      postoperatively improved at 1.1 and 1.7 levels, respectively. There were two hook
      dislodgements in the thoracic spine, one in each group, while there was no screw
      failure in group B. There was neither pseudarthrosis nor neurologic deterioration
      following surgery. Visual Analog Pain Scale and Short Form-36 scores were equally
      improved and did not differ between the two groups. The use of pedicle screws in
      the lumbar spine to stabilize the lowermost end of a long rigid construct applied
      for A3, B, and C thoracolumbar injuries was advantageous when compared with that
      using hook claws in the lumbar spine because the constructs with screws restored
      and maintained the fractured anterior vertebral body height better than the hooks
      without subsequent loss of correction and safeguarded postoperatively a
      continuous SCC at the injury level.

PMID- 15167336
TI  - Prospective evaluation of thoracic pedicle screw placement using fluoroscopic
      imaging.
AB  - BACKGROUND: In this prospective 18-month study, 29 patients underwent posterior
      thoracic instrumentation with placement of 209 transpedicular screws guided by
      intraoperative fluoroscopic imaging and anatomic landmarks. We assessed the
      safety, accuracy, complications, and early stability of this technique. METHODS:
      Pedicle and pedicle-rib units were measured, and screw cortical penetrations were
      graded on anatomy and depth of penetration. All 29 patients underwent
      preoperative computed tomographic (CT) imaging, and 28 underwent postoperative CT
      imaging (199/209 screws). RESULTS: From T2 to T12, screw diameters were >or=5 mm
      with mean medial screw angulation measuring 20-25 degree. Of the 209 screws
      placed from T1 to T12, 111 had diameters greater than or equal to the pedicle
      width. From T3 to T9, the mean diameter of the pedicle screws exceeded the mean
      pedicle width. Lateral pedicle wall penetration occurred significantly more often
      than superior, inferior, and medial pedicle wall penetrations and anterolateral
      vertebral body penetration. Five of six high-risk screw penetrations occurred in
      one patient when intraoperative technique was compromised. We observed no new
      postoperative neurologic deficits, visceral injuries, or pedicle screw
      instrumentation failures. The three high-risk anterolateral vertebral body
      penetrations at T1 and T2 were associated with a significantly decreased mean
      screw transverse angle; the three high-risk medial pedicle wall penetrations
      occurring from T3 to T9 were associated with a significantly increased mean screw
      transverse angle. Among all 26 patients available at postoperative follow-up
      (mean 11.9 months), the mean loss of kyphosis correction was 2.0 degree.
      CONCLUSIONS: Guided by intraoperative fluoroscopic imaging and anatomic
      landmarks, thoracic pedicle screws can be placed safely. Early clinical follow-up
      reveals excellent results with minimal loss of kyphosis correction.

PMID- 15167337
TI  - Biomechanical study of adjacent intervertebral motion after lumbar spinal fusion
      and flexible stabilization using polyethylene-terephthalate bands.
AB  - Thirty fresh-frozen calf cadaveric spinal specimens (L3-L6) were used to
      investigate the effect of flexible stabilization and fixation on the adjacent
      intervertebral motion segment. The intact spine that had not been subjected to
      injury was used for comparison as control. The destabilized spine was made up of
      specimens from which the bilateral facet joints and the supraspinous and
      interspinous ligaments were removed. The flexible stabilized spine was applied
      with pedicle screws and polyethylene-terephthalate bands, and the fixed spine was
      applied with pedicle screws and rods at the L4-L5 segment. The range of motion
      (ROM) was measured under flexion, extension, and bilateral bending moments, and
      the ROM ratio (ROM of each model versus ROM of the comparison model) was
      calculated at L3-L4, L4-L5, and L5-L6 segments. In the flexible stabilized spine,
      the restriction of motion was high under flexion and bilateral bending moments,
      and the mobility of the adjacent intervertebral motion segments approximated the
      normal lumbar vertebra. In the fixed spine, the ROM ratio increased at the
      cranial and caudal adjacent segments.

PMID- 15167338
TI  - The course of the nerve root in the neural foramen and its relationship with
      foraminal entrapment or impingement in adult patients with lumbar isthmic
      spondylolisthesis and radicular pain.
AB  - The purpose of this study was to demonstrate the course of a nerve root in the
      neural foramen and its relationship with foraminal entrapment or impingement in
      19 adult patients with isthmic spondylolisthesis and radicular pain. Myelo
      computed tomography and magnetic resonance imaging showed that the course of the
      nerve root was normal (ie, medial and then inferior, along the pedicle) in 10
      patients and was deviated posteriorly in 9 patients. The patients with a normal
      nerve root course (N-NRC) had either a bony callus projecting medially into the
      spinal canal (n = 6) or a low mean percentile of vertebral slip (n = 4; 13.9 +/-
      1.3). Those nine patients with a posteriorly deviated nerve root course (PD-NRC)
      had no medially projecting bony callus in the spinal canal but had a higher mean
      percentile of vertebral slip (n = 9; 31.5 +/- 10.1; P = 0.005). In the neural
      foramen, nerve roots of the N-NRC patients were entrapped craniocaudally between
      the pedicle and superior part of the intervertebral disc. In contrast, nerve
      roots of the PD-NRC patients were impinged ventrodorsally between the
      posterosuperior part of the intervertebral disc and either bony callus projecting
      inferiorly toward the neural foramen or fibrocartilaginous mass arising around
      the isthmic defect. The foraminal craniocaudal entrapment and ventrodorsal
      impingement highly agreed with the side of radicular pain (kappa= 0.73, P <
      0.001). Our results demonstrate that the medially projecting bony callus and the
      percentile of vertebral slip affect the course of the nerve root in the neural
      foramen, which in turn determines the foraminal craniocaudal entrapment or
      ventrodorsal impingement. These two mechanisms, based on the course of the nerve
      root, correlate well with the side of radicular pain.

PMID- 15167339
TI  - Effects of cervical cages on load distribution of cancellous core: a finite
      element analysis.
AB  - METHODS: The study was designed to analyze the load distribution of the
      cancellous core after implantation of vertical ring cages made of titanium,
      cortical bone, and tantalum using the finite element (FE) method. The intact FE
      model of C5-C6 motion segment was validated with experimental results. RESULTS:
      The percentage of load distribution in cancellous core dropped by about one-third
      of the level for the intact model after the cage implantation. The difference
      among cages made of different materials (or different stiffnesses) was not very
      obvious. CONCLUSIONS: These results implied that the influence of the cage on the
      load transfer in the cancellous core is greatly related to the cage's dimensions
      and position within the intervertebral space. The dimension and position of the
      cage that least disturb the load distribution in cancellous core could be
      criteria in cage development.

PMID- 15167340
TI  - CT density measurement of bone graft within an intervertebral lumbar cage:
      increase of hounsfield units as an indicator for increasing bone mineral content.
AB  - Radiographic assessment of lumbar interbody fusion is difficult, especially in
      the presence of cages and metal artifacts. The purpose of this study is to assess
      whether impacted bone chips in intervertebral lumbar cages show a tendency toward
      increased attenuation on postoperative computed tomography (CT) scans as a sign
      of ongoing revascularization and increased bone mineral content inside the cage.
      Twenty-one patients with single- or double-level lumbar fusion underwent CT
      scanning 1-44 months postoperatively. CT attenuation of bone inside the cage was
      measured with Hounsfield units. Intra- and interobserver variability were
      evaluated. Regression analysis showed an increase of 7.5 HU/month postoperatively
      for an initial value of 615 HU. Intra- and interobserver variability showed an
      interclass coefficient of 0.97. CT attenuation of bone graft inside an
      intervertebral cage increases in the postoperative period. Hounsfield unit
      measurement can be performed with a high degree of accuracy and reproducibility
      and may in the future provide a useful tool in studying cage contents in
      individual patients.

PMID- 15167341
TI  - Osteoporotic spinal deformity: a biomechanical rationale for the clinical
      consequences and treatment of vertebral body compression fractures.
AB  - This review article develops a biomechanical rationale for the clinical
      consequences and treatment of osteoporotic vertebral body compression fracture.
      In patients with osteoporotic vertebral fractures and spinal deformity, altered
      spinal biomechanics and global spinal imbalance are important factors in the
      increased morbidity and mortality reported in this population. Severe spinal
      deformity impairs physical functioning, health, and quality of life. The spinal
      deformity itself, independent of pain, is a significant cause of disability.
      Spinal deformity is also an independent risk factor for hip fracture. Treatments
      directed at osteoporotic vertebral compression fractures should ideally address
      spinal deformity as well as pain. Balloon kyphoplasty, the minimally invasive
      technique of reduction and internal fixation of osteopenic vertebral body
      compression fractures that addresses pain and spinal deformity, is discussed.

PMID- 15167342
TI  - Lumbar discography: should we use prophylactic antibiotics? A study of 435
      consecutive discograms and a systematic review of the literature.
AB  - BACKGROUND: Lumbar discography can be used in the diagnostic work-up of
      degenerative spine disease. The most serious complication is discitis, believed
      to be due to penetration of the disc by a needle contaminated with skin flora.
      The use of prophylactic antibiotics has been advocated, although there is great
      concern regarding their efficacy and possible adverse effects on disc cells.
      METHODS: In the current study, the incidence of postdiscography discitis without
      the use of prophylactic antibiotics was studied in a consecutive patient group.
      Additionally, a systematic literature review was performed using strict criteria:
      1). Discography was performed by means of a two-needle technique, 2).
      complications such as discitis were specifically looked for at follow-up, and 3).
      the exact numbers of patients and those lost to follow-up were reported. RESULTS:
      The clinical results of 200 patients with 100% follow-up for a minimum period of
      3 months showed no case of discitis. In the literature review, 10 studies were
      selected. Nine studies without prophylactic antibiotics reported an overall
      incidence of 12 cases in 4891 patients (0.25%) or 12770 discs (0.094%). The only
      study with prophylactic antibiotics (127 patients) showed no case of discitis.
      CONCLUSIONS: Regarding the small number of patients in the only study in which
      antibiotics were used and the overall low incidence of postdiscography discitis,
      not enough evidence was found that prophylactic antibiotics can prevent discitis.
      It was concluded that in lumbar discography by means of a two-needle technique
      without prophylactic antibiotics, the risk of postdiscography discitis is minimal
      and there is not enough support from the literature to justify the routine use of
      prophylactic antibiotics.

PMID- 15167343
TI  - Bowel injury as a complication of microdiscectomy: case report and literature
      review.
AB  - Intestinal injury is a rare complication of lumbar disc surgery, resulting from
      inadvertent penetration of the anterior annulus fibrosus and anterior
      longitudinal ligament. Patients typically complain of abdominal pain and
      distention developing over the course of several days. Imaging with plain upright
      chest radiographs or abdominal computed tomography may demonstrate free air in
      the abdominal cavity. We report a case of intestinal perforation after
      microscopic lumbar discectomy and present the diagnostic postoperative imaging.
      In addition, we review the relevant literature and discuss techniques that may be
      employed to avoid this complication.

PMID- 15167344
TI  - High-dose methotrexate and asparaginase for the treatment of children with acute
      lymphoblastic leukemia: why and how?

PMID- 15167345
TI  - Pretreatment cystatin C in children with malignancy: can it predict chemotherapy
      induced glomerular filtration rate reduction during the induction phase?
AB  - BACKGROUND: Monitoring of kidney function is essential during chemotherapy. Serum
      creatinine is of limited value in early detection of renal insufficiency. The
      cystatin C level has been proved to be a good marker for detection of mild
      reduction in glomerular filtration rate. PURPOSE: To evaluate the validity of the
      pretreatment serum cystatin C level in predicting significant reduction of the
      glomerular filtration rate during the induction phase of chemotherapy. PATIENTS
      AND METHODS: Serum levels of cystatin C and creatinine and corrected creatinine
      clearance were assessed in 34 children with different types of malignancy just
      before the start of chemotherapy and again in 33 of them 1 month later. Patients
      were compared with 14 healthy controls of matched age and sex. RESULTS: Before
      chemotherapy, all patients when compared with controls had normal levels of
      cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine
      clearance (P = 0.76). One month after chemotherapy, patients showed a significant
      increase in their cystatin C levels (P < 0.001) and a significant decrease in
      their corrected creatinine clearance (P < 0.001). However, creatinine levels did
      not change significantly (P = 0.65). Corrected creatinine clearance negatively
      correlated significantly with both cystatin C and creatinine levels (r = -0.622,
      P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1
      month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009,
      respectively). When pretreatment levels of cystatin C and creatinine were used to
      predict patients who developed a reduction in corrected creatinine clearance of
      more than 20% after therapy, only the cystatin C level was statistically
      significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%,
      specificity of 63%, and overall accuracy of 74% was suggested. CONCLUSIONS:
      Children with malignant diseases develop significant reduction in their
      glomerular filtration rate during the induction phase of chemotherapy, although
      their serum creatinine level may not change significantly. Cystatin C, as a more
      sensitive marker than creatinine for the assessment of glomerular filtration
      rate, can be used to predict patients who would have a higher risk of renal
      impairment during the induction phase of chemotherapy and who thus would require
      more frequent renal function assessment to consider adjustment of the
      chemotherapy dose if indicated.

PMID- 15167346
TI  - Telomere length and telomerase activity: variations with advancing age and
      potential role in childhood malignancies.
AB  - Telomeres, representing the chromosome nucleoprotein tails, shorten during each
      cell division due to the inability of conventional DNA polymerases to completely
      replicate the chromosome termini. When telomeres become critically short, cells
      are directed to exit from the cell division cycle (replicative senescence).
      Telomerase is a reverse transcriptase that synthesizes telomeric sequences,
      thereby prolonging the lifespan of cells. Telomere length and telomerase activity
      expression vary significantly in different normal somatic tissues and age groups.
      In many childhood malignancies (ie, acute leukemias and solid tumors), telomere
      length and telomerase activity of the malignant cell population may be correlated
      with the disease outcome and thus may be promising tools in evaluating prognosis
      and monitoring treatment progress. Finally, telomerase inhibition by using
      several strategies (ie, antisense oligonucleotides) represents a potentially
      valuable target for antitumor therapy in the near future.

PMID- 15167347
TI  - MRI follow-up and natural history of avascular necrosis of the femoral head in
      Kuwaiti children with sickle cell disease.
AB  - PURPOSE: : To document the MRI progression and the natural history of avascular
      necrosis of the femoral head (AVNFH) in Arab children with sickle cell disease.
      PATIENTS AND METHODS: Twenty-three SS and 7 SbetaThal patients (aged 6-17 years)
      were screened for AVNFH between 1998 and 1999. Eight (26.7%) were identified with
      varying degrees of AVNFH. Seventeen of the original 30 patients have now been
      followed for 1 to 4 (mean 2.0 +/- 1.2) years, with repeat MRI of the hips. Spin
      echo T1-and T2-weighted images and T2 fat-saturation sequences were obtained
      using a 1.5-Tesla GE unit with superconductors. AVNFH was graded I (mild), II
      (moderate), or III (severe). RESULTS: Eleven (64.7%) of the 17 patients had
      significant progression of their lesions; at the initial study, 9 were normal, 7
      were grade I, 1 was grade II, and none was grade III. At the end of the follow-up
      period, two were normal, seven were grade I, one was grade II, and seven were
      grade III. Of the nine who were initially normal, two still had no lesions, while
      four were grade I and three were grade III on follow-up. Of the seven who were
      classified as grade I initially, four remained at grade I, one moved to grade II,
      and two became grade III. The one patient who was initially grade II progressed
      to III. CONCLUSIONS: AVNFH is a common, chronic, and unrelenting complication in
      children with sickle cell disease, and it is usually progressive.

PMID- 15167348
TI  - Life after cancer in childhood: social adjustment and educational and vocational
      status of young-adult survivors.
AB  - PURPOSE: To evaluate the long-term social effect of illness and its treatment on
      young-adult survivors of pediatric cancer by addressing a selection of general
      social adjustment criteria. METHODS: In a cross-sectional case-control study, 30
      young-adult survivors of childhood cancer were compared with (1). controls with
      no history of serious illness, matched by sex, age, and geographic area of
      residence, and (2). general population norms on the subject of educational and
      vocational factors, habitation, family/partner relationships, parenthood, and
      leisure activities. RESULTS: The educational status of survivors was similar to
      that of controls, although a smaller proportion of the patients expressed
      concrete plans for future vocational or educational advancement. Survivors had
      less frequently entered higher education compared with general population norms.
      A longer duration of treatment was related to a lower estimated socioeconomic
      level, and poor psychological coping with the illness experience was associated
      with the fact that they were still living with their parents, a shorter
      education, and a lower socioeconomic level. CONCLUSIONS: The social, vocational,
      and educational adjustment of relapse-free survivors from childhood cancer
      appears as only moderately, if at all, negatively affected by the illness and
      treatment history. However, the treatment intensity and particularly the
      survivors' coping with their illness experience may influence their ability to
      achieve long-term social goals. These findings suggest that special attention
      should be given to matters concerning education and partner relationships at long
      term follow-up of pediatric cancer patients.

PMID- 15167349
TI  - Flow cytometric diagnosis of X-linked hyper-IgM syndrome: application of an
      accurate and convenient procedure.
AB  - Hyper-IgM (HIM) syndrome encompasses a family of congenital immunodeficiency
      states characterized by frequent infections and markedly low serum levels of IgG,
      IgA, and IgE but normal or elevated levels of IgM. Many patients have
      neutropenia. The major defect shared by all forms of HIM syndrome is a failure of
      immunoglobulin isotype-switching. Recently, a flow cytometric assay was described
      in the immunology literature for diagnosis of patients with inherited X-linked (X
      HIM) syndrome. Using this assay, activated CD4 peripheral blood T lymphocytes
      from two patients suspected of having HIM syndrome, and from their mothers, were
      subjected to immunofluorescent flow cytometric analysis for the expression of
      CD40 ligand (CD154 antigen). Test results established the diagnosis of X-HIM
      syndrome that was inherited in one patient and spontaneous in the other. The
      authors' experience illustrates that the flow cytometric assay used and described
      in detail here can facilitate an accurate and timely diagnosis of X-HIM syndrome.
      Because the assay can be carried out in most clinical flow cytometry facilities,
      it lends itself to use by pediatric hematologists in the standard evaluation of
      patients whose differential diagnosis includes that disorder. The authors hope
      this report will raise awareness of the value of this procedure.

PMID- 15167350
TI  - Successful treatment of congenital systemic juvenile xanthogranuloma with
      Langerhans cell histiocytosis-based chemotherapy.
AB  - Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans
      cell histiocytosis (LCH), usually presents in young children as spontaneously
      regressing cutaneous lesions. However, the systemic type of JXG is difficult to
      treat in newborn infants, and fatal cases have been reported. In the patient
      described here, solid masses were discovered by fetal sonography during the 38th
      gestational week. At birth she had multiple tumors on the back, cheek, and hip as
      well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory
      results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy.
      Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and
      dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with
      systemic JXG by histopathologic findings of the hip mass. The LCH-based
      multiagent chemotherapy including cytarabine, vincristine, methotrexate, and
      prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and
      is currently doing well as a normally developing 2-year-old.

PMID- 15167351
TI  - Hemophagocytic syndrome and hepatosplenic gammadelta T-cell lymphoma with
      isochromosome 7q and 8 trisomy.
AB  - The authors describe a 15-year-old boy with hepatosplenic gammadelta T-cell
      lymphoma associated with hemophagocytic syndrome (HPS) along with isochromosome
      7q and trisomy 8. He presented with prolonged fever, mild anemia,
      thrombocytopenia, and hepatosplenomegaly. Physical examination, radiography, and
      ultrasound tomography revealed no lymphoadenopathy. He had elevated levels of
      serum ferritin, interferon-gamma, soluble interleukin-2 receptor, and interleukin
      6. Bone marrow aspirate showed hypercellularity with 50% lymphoblasts and
      erythrophagocytosis of macrophage. A cytogenetic study of bone marrow revealed an
      abnormal karyotype, 47,XY,I(7q),+8, in 5/30 cells. Clonal rearrangement of the
      genes for T-cell receptor gamma and delta chains was elucidated by polymerase
      chain reaction. He achieved a complete remission after intensive chemotherapy and
      underwent splenectomy 18 months after diagnosis. Although the patient was
      clinically in remission, minimal residual disease (MRD) was detected in the
      removed spleen by polymerase chain reaction. This might mean that this type of
      lymphoma is refractory, as reported previously, and might indicate that marrow
      ablative therapy is needed to achieve a cure. The present case illustrates the
      usefulness of MRD analysis, and MRD studies in this group of disorders may be
      helpful in the decision of whether to continue a more aggressive therapeutic
      approach.

PMID- 15167352
TI  - Granulocyte colony-stimulating factor-responsive chronic neutropenia in cartilage
      hair hypoplasia.
AB  - : Chronic neutropenia is common in children with cartilage-hair hypoplasia (CHH).
      The authors describe a 6-year-old with severe CHH, moderate neutropenia
      associated with serum IgG antibodies directed against Fcgamma-RIIIb (NA1/2), and
      frequent bacterial infections. In this patient, long-term administration of
      granulocyte colony-stimulating factor increased peripheral neutrophil counts and
      prevented recurrent hospitalizations for bacterial lower respiratory tract
      infections.

PMID- 15167353
TI  - Unrelated umbilical cord blood transplantation for an infant with beta
      thalassemia major.
AB  - BACKGROUND: beta-thalassemia major, one of the most prevalent hemoglobinopathies
      throughout the world, can be cured by allogeneic stem cell transplantation
      therapy. Many patients, however, lack a suitably matched related donor. Unrelated
      umbilical cord blood can be used as an alternative stem cell source for some of
      these patients. This report describes the successful transplantation of a 2-month
      old infant with beta-thalassemia major using partially HLA-matched unrelated
      umbilical cord blood. METHODS: After cytoreduction with busulfan,
      cyclophosphamide, and antithymocyte globulin (ATG), the patient underwent
      transplantation at the age of 2 months with a 4/6 HLA matching umbilical cord
      blood unit from an unrelated donor. RESULTS: The patient engrafted promptly with
      100% donor chimerism. His only major complication was an autoimmune hemolytic
      anemia that resolved 2 years after transplantation. He is currently surviving,
      event-free, 5 years after transplantation with normal growth and cognitive
      development and full donor chimerism without evidence of beta-thalassemia.
      CONCLUSIONS: Umbilical cord blood transplantation from related and unrelated
      donors should be considered for patients with beta-thalassemia major who lack
      traditional bone marrow donors. As most newborns undergo screening for
      hemoglobinopathies, those with disease could be transplanted early in life before
      experiencing the morbidity and mortality caused by transfusion therapy,
      alloimmunization, and iron overload, increasing the likelihood of successful
      transplantation therapy.

PMID- 15167354
TI  - Effects of intraventricular methotrexate on folate, adenosine, and homocysteine
      metabolism in cerebrospinal fluid.
AB  - Methotrexate (MTX) is an antifolate that affects many metabolic pathways. MTX may
      cause neurologic toxicity, but the biochemical effects of MTX on the central
      nervous system (CNS) are poorly characterized. The authors studied serial
      cerebrospinal fluid (CSF) samples from a child during two courses of
      intraventricular MTX and found a rapid and reproducible depletion in CSF of
      reduced folates and S-adenosylmethionine that was accompanied by marked increases
      in homocysteine and adenosine. No sulfur-containing excitatory amino acids were
      detected. This study demonstrates multiple profound effects of MTX on CNS
      metabolism and provides insight to the pathogenesis of MTX neurotoxicity.

PMID- 15167355
TI  - Parameningeal rhabdomyosarcoma in a patient with Costello syndrome.
AB  - Costello syndrome, a rare entity with multiple congenital anomalies, has been
      associated with a high incidence of benign and malignant tumors, particularly
      rhabdomyosarcoma. Although the head and neck is the most common site for
      rhabdomyosarcomas in children, only one other case in the literature has been
      reported of a head and neck rhabdomyosarcoma in a Costello patient. The authors
      describe a 3-year-old with a parameningeal infratemporal fossa rhabdomyosarcoma.
      Management is discussed with particular attention to the difficulties encountered
      due to the congenital heart abnormalities associated with the syndrome.

PMID- 15167357
TI  - Congenital Langerhans cell histiocytosis: the self-healing variety.
AB  - Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare variant
      of Langerhans cell histiocytosis, presenting at birth or in the neonatal period
      with cutaneous lesions that involute spontaneously. Affected infants are
      otherwise well with no systemic illness. A case of CSHLCH, probably the first
      case report from India, is described. The patient presented on the third day of
      life with multiple papulonodular lesions over the body, with no systemic
      involvement. The lesions spontaneously regressed by 6 months of age, with no
      evidence of relapse at 1 year of age. Although CSHLCH is a benign and self
      limited condition, long-term follow-up for evidence of relapse is emphasized.

PMID- 15167356
TI  - Pulmonary hypertension complicating bone marrow transplantation for idiopathic
      myelofibrosis.
AB  - Idiopathic myelofibrosis is a rare hematologic disorder that is occasionally
      associated with pulmonary hypertension and has been cured with bone marrow
      transplantation (BMT). Most cases occur in older adults, but children with
      similar clinical and pathologic findings have been described. The authors
      describe a critically ill male infant with idiopathic myelofibrosis and subtle
      findings suggestive of pulmonary hypertension who was treated with BMT after
      failing to respond to chemotherapy. After BMT, the patient's clinical course
      improved in all respects, but he ultimately died of progressive pulmonary
      hypertension.

PMID- 15167358
TI  - Gut inflammation: impact on gastrointestinal and systemic diseases. Proceedings
      of the 1st ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology
      and Nutrition) Capri Meeting. May 27-29, 2004. Capri, Italy.

PMID- 15167359
TI  - CD1d-restricted T cell pathways at the epithelial-lymphocyte-luminal interface.
AB  - The mucosal-associated lymphoid tissues, including the gut-associated lymphoid
      tissues, represent a tightly regulated environment that, on the one hand, must
      resist microbial invasions and on the other hand, when perturbed, causes
      inflammation such as that associated with inflammatory bowel disease. One type of
      regulatory cellular subset that has recently gained attention in this compartment
      is the subset of T cells that are associated with CD1d-restricted responses.
      Recently, CD1d-restricted T cells have been increasingly appreciated to play a
      significant role in mucosal tissues of the intestine and lung, for example. In
      this review, we focus on recent observations in the characteristics of CD1d
      restricted pathways in mucosal compartments after a brief introduction to the
      biology of CD1d and CD1d-restricted T cells.

PMID- 15167360
TI  - Anatomical and cellular basis of immunity and tolerance in the intestine.

PMID- 15167361
TI  - The traffic of mucosal lymphocytes to extraintestinal sites.

PMID- 15167362
TI  - Immunoregulation in the liver and its extrahepatic relevance.
AB  - As well as being a metabolic factory, the liver also functions as a powerful
      immune organ constantly engaged in local immune responses. In addition, it has a
      significant influence on systemic immunity. The hepatic immune system recognises
      and responds to pathogens, as well transformed and metastatic cells, while at
      same time tolerising harmless dietary and commensal antigens. The molecular
      mechanisms by which these different discriminatory, regulatory and effector
      functions are mediated are only now beginning to be identified.

PMID- 15167363
TI  - Gliadin as stimulator adaptive and innate immune responses in celiac disease.

PMID- 15167364
TI  - The gut as site of production of autoimmune antibodies.

PMID- 15167365
TI  - Intestinal immunity and type 1 diabetes.

PMID- 15167366
TI  - The gut-skin axis.

PMID- 15167367
TI  - Spondyloarthropathy and gut inflammation.

PMID- 15167368
TI  - Dietary proteins and mechanisms of gastrointestinal diseases: gliadin as a model.

PMID- 15167369
TI  - Coeliac disease and extraintestinal autoimmunity.

PMID- 15167370
TI  - Gut inflammation and extraintestinal manifestation of food allergy.

PMID- 15167371
TI  - Immunomodulation of mucosal inflammation.

PMID- 15167373
TI  - Probiotics and the immune response: how much can we expect?

PMID- 15167372
TI  - The use of oral tolerance in the therapy of chronic inflammatory/autoimmune
      diseases.

PMID- 15167375
TI  - Inflammation in irritable bowel syndrome: curiosity or culprit.

PMID- 15167374
TI  - Inflammatory cells and the regulation of gut motility.

PMID- 15167376
TI  - The Rome criteria for functional gastrointestinal disorders: a critical
      reappraisal.

PMID- 15167377
TI  - Upper functional gastrointestinal disorders in a pediatric population.

PMID- 15167378
TI  - Lower functional gastrointestinal disorders in a paediatric population.

PMID- 15167379
TI  - Diagnosing and managing functional symptoms in the child with inflammatory bowel
      disease.

PMID- 15167380
TI  - Central nervous system approaches for treating functional disorders: how, when,
      and why?

PMID- 15167382
TI  - Functional foods in pediatric disease: when and why?

PMID- 15167381
TI  - Advances in pharmacological treatments of IBS.

PMID- 15167383
TI  - New and emerging therapies for short bowel syndrome in children.

PMID- 15167384
TI  - Prebiotics and immune responses.

PMID- 15167385
TI  - Food as a source of dioxin exposure in the residents of Bien Hoa City, Vietnam-
      Schecter et al.

PMID- 15167387
TI  - Reducing the cost of hepatitis B vaccination programs.

PMID- 15167388
TI  - Effects of airborne World Trade Center dust on cytokine release by primary human
      lung cells in vitro.
AB  - There are continuing concerns regarding the respiratory health effects of
      airborne particulate matter (PM) after the destruction of the World Trade Centre
      (WTC). We examined cytokine (interleukin [IL]-8, IL-6, tumor necrosis factor
      alpha) release by primary human lung alveolar macrophages (AM) and type II
      epithelial cells after exposure to WTC PM2.5 (indoor and outdoor), PM10-2.5
      (indoor), and PM53-10 (outdoor), fractionated from settled dusts within 2 months
      of the incident. There was an increase in AM cytokine/chemokine release at 5
      and/or 50 microg/well WTC PM, which fell at 500 microg/well. Type II cells did
      not release tumor necrosis factor-alpha, and the increase in IL-8 and IL-6,
      although significant, was lower than that of AM. Respirable PM generated by the
      WTC collapse stimulates inflammatory mediator release by lung cells, which may
      contribute to the increased incidence of respiratory illness since September 11th
      2001.

PMID- 15167389
TI  - Relationship of body mass index and physical activity to health care costs among
      employees.
AB  - This study examined the relationship between physical activity and health care
      costs by different weight groups. The study sample consisted of 23,490 active
      employees grouped into normal weight, overweight, and obese categories. After
      adjustment for covariates, physically moderately active (1 to 2 times/week) and
      very active (3 + times/week) employees had approximately $250 less paid health
      care costs annually than sedentary employees (0 time/week) across all weight
      categories. The difference was approximately $450 in the obese subpopulation. The
      maximum possible savings was estimated to be 1.5% of the total health care costs
      if all obese sedentary employees would adapt a physically active lifestyle. As a
      strategy to control escalating health care costs, wellness programs should
      facilitate engagement in moderate physical activity of at least 1 to 2 times a
      week among sedentary obese people and help them to maintain this more active
      lifestyle.)

PMID- 15167390
TI  - Characteristics of hepatocellular carcinoma in a high arsenicism area in Taiwan:
      a case-control study.
AB  - Arsenic contamination of drinking water is noticeably linked to the occurrence of
      skin, bladder, lung cancers, and hepatocellular carcinoma (HCC). Blackfoot
      disease (BFD) caused by arsenicosis is endemic in southwestern Taiwan, where
      artesian well water contains high concentrations of arsenic, and mortality from
      HCC shows a dose-response increase by concentration of arsenic in the well water.
      This case-control study was conducted to examine the clinical characteristics of
      HCC patients of BFD-endemic area. A total of 65 HCC cases (54 men and 11 women)
      were recruited from the BFD-endemic areas. The clinicopathological features were
      compared with 130 age- and sex-matched HCC control patients from non-BFD-endemic
      areas. Characteristics analyzed included hepatitis viral infection status,
      hepatitis activity, liver function, histological findings, computed tomography
      scan characteristics, and patient survival. No differences were observed between
      HCC patients or their tumors, from study and control areas.

PMID- 15167392
TI  - Effects of job insecurity from a workplace closure threat on fatigue and
      psychological distress.
AB  - The aim of this study was to prospectively investigate the effect of potential
      workplace closure, an externally attributed form of job insecurity, on fatigue
      and psychological distress. In April 1999, the minister responsible announced
      that a governmental agency would close down one of its two locations. Baseline
      data from the employees were available before the closure announcement (n = 574)
      because they were enrolled in the Maastricht Cohort Study on "Fatigue at Work."
      In the closure group, the relative risk for becoming a psychological distress
      case was 1.61 (95% confidence interval [CI] = 1.27-2.05) during 13 months after
      the closure threat. Within the closure group, a difference in relative risk for
      psychological distress was observed between employees who self reported an
      increase in job insecurity (relative risk = 1.85; 95% CI = 1.41-2.42) and
      employees who did not report an increase in job insecurity (relative risk 1.14;
      95% CI = 0.58-2.24)

PMID- 15167394
TI  - Vermont granite mortality study: an update with an emphasis on lung cancer.
AB  - This mortality study extends the period of observation of an article published in
      1988 of 5414 workers in Vermont granite sheds and quarries to assess whether
      previously reported reductions in silicosis and tuberculosis mortality were
      maintained. The relationship between lung cancer and quartz exposure is also
      examined by comparing mortality in workers hired before and after 1940, when dust
      controls were introduced and exposures were reduced by 80% to 90%. Before 1940,
      general stone shed air contained 20 million particles/cubic foot (mppcf)
      (approximately equivalent to 0.2 mg/m of quartz), and pneumatic chisel workers
      were exposed on average to 60 mppcf (approximately equivalent to 0.6 mg/m of
      quartz). Other workers had variable exposures. After 1940, a period of decline
      occurred in dust levels and then stabilized in approximately 1955, when average
      dust levels were 5 to 6 mppcf (equivalent to 0.05-.06 mg/m of quartz). Dust
      exposures in the Vermont industry is considered to be free of confounding
      occupational substances such as arsenic, although cigarette smoking was common.
      By the end of 1996, 2539 workers, or 46.9% of the cohort, had died. There were no
      silicosis deaths in workers hired after 1940 who were exposed only in the Vermont
      granite industry, illustrating the effect of lowering quartz exposures.
      Tuberculosis caused 2 deaths in those hired after 1940 (standardized mortality
      ratio [SMR] = 0.52; not significant). Overall lung cancer mortality was elevated
      in shed workers who had been exposed both to high levels of quartz before 1940
      and to the lower levels prevailing after 1940 (SMR = 1.32; P < 0.01). Quarry
      workers did not show an excess of lung cancer (SMR = 0.73; not significant). When
      shed workers with high and low exposure histories (before and after 1940) but
      with comparable latency and tenure were contrasted, lung cancer mortality was
      similar. Differing levels of quartz exposure, which resulted in large differences
      in the mortality experience from silicosis, did not result in differences in lung
      cancer mortality. The results do not support the hypothesis that granite dust
      exposure has a causal association with lung cancer.

PMID- 15167393
TI  - Effectiveness of crime prevention through environmental design in reducing
      criminal activity in liquor stores: a pilot study.
AB  - Liquor store employees experience disproportionately higher rates of workplace
      injury death than employees in any other retail setting. However, efforts to
      introduce workplace violence prevention programs into liquor stores have been
      minimal. This study examines the effectiveness of a Crime Prevention Through
      Environmental Design intervention in reducing criminal activity in Santa Monica,
      California liquor stores. Nine stores enrolling in the study received an
      individualized intervention safety plan; the remaining 13 served as a comparison
      group. Mixed-effects Poisson regression was used to examine intervention
      effectiveness. The largest reductions in criminal activity occurred for robbery
      and shoplifting outcomes. We conclude that the Crime Prevention Through
      Environmental Design program reduced crime and injury in liquor stores and
      educated small businesses about the risks associated with retail violence and the
      countermeasures that can be taken.

PMID- 15167395
TI  - Immunologic response to inhaled endotoxin: changes in peripheral cell surface
      markers in normal individuals.
AB  - Monocyte cell surface CD14 increases following both in vitro challenge with
      lipopolysaccharide (LPS) and exposure to organic dusts. We investigated 9
      volunteers, mean age 39 years (range, 29-53 years). Each inhaled increasing
      concentrations of lipopolysaccharide (0.5 microg, 5.0 microg, and 20 microg).
      Monocyte cell surface CD14 (expressed as mean linear fluorescence) was measured
      before and after using flow cytometry. Upregulation of CD14 (up to 6 hours after
      LPS exposure) did not differ significantly between LPS (mean, 35.8; standard
      deviation [SD]; 54.3), n = 7 after 20 l g LPS) in comparison to placebo (39.3
      [49.0]; n = 7). Maximum mean (SD) percentage CD14 upregulation up to 6 hours
      after challenge differed, but not significantly between those experiencing a
      clinically significant event (58.4 [49.2]) in comparison to those who did not
      (13.8, [43.2]; P = 0.27). Two individuals with a marked clinical response
      developed marked CD14 upregulation after exposure to LPS.

PMID- 15167396
TI  - Multidisciplinary pain center outcomes in Washington State Workers' Compensation.
AB  - We conducted this study to evaluate the clinical and disability status of injured
      workers 4.6 years after undergoing multidisciplinary pain center evaluation,
      comparing subjects who received treatment to subjects who were evaluated only.
      Three hundred injured workers were selected for a telephone survey; 150 had
      received pain center treatment and 150 had been evaluated but not treated. The
      survey included the SF-12, and questions about subjects' pain intensity and
      current work status. A workers' compensation database indicated the disability
      status of subjects. The response rate was 50%. In multivariate analyses, treated
      and evaluated-only subjects did not differ significantly in disability status,
      pain intensity, SF-12 scores, or current work status. At 4.6 years follow up,
      there was no evidence that pain center treatment affects either disability status
      or clinical status of injured workers.

PMID- 15167397
TI  - Identification of occupational cancer risks in British Columbia: a population
      based case-control study of 769 cases of non-Hodgkin's lymphoma analyzed by
      histopathology subtypes.
AB  - We have, as part of a program aimed at detecting occupational risk factors in
      British Columbia, collected lifetime occupational histories as well as
      information on lifetime cigarette smoking and alcohol consumption from 15,643
      incident cancer cases, of whom 782 had a diagnosis of non-Hodgkin's lymphoma
      (NHL). Occupational risks for this cancer site are examined using a matched case
      control study design, and the results are presented in this report for all cases
      and for histopathology subtypes. The results of our study indicate excess NHL
      risk, particularly for a number of occupations that involve exposures to
      electromagnetic fields, treated and fresh wood, metals, and solvents.

PMID- 15167398
TI  - Predictors of successful work role functioning after carpal tunnel release
      surgery.
AB  - This study identified the clinical, individual, and workplace predictors of
      successful work role functioning (WRF) after carpal tunnel release surgery
      (CTRS). A community-based cohort (n = 197) was followed for 6 months post-CTRS.
      Predictors of successful WRF were analyzed prospectively using ordinal logistic
      regression. Baseline WRF predicted successful WRF at 2 months, whereas being
      depressed and a workers' compensation claimant predicted being out of work.
      Baseline WRF, improved self-efficacy, and a supportive organization predicted 6
      month successful WRF. Supportive organizations have an impact on the
      effectiveness of medical interventions for CTS. The significance of improved self
      efficacy at 6 months and depression at 2 months postsurgery highlights the
      importance of psychosocial management of musculoskeletal disorders.

PMID- 15167399
TI  - Hydrofluoric acid releases in 17 states and the acute health effects associated,
      1993-2001.
AB  - Hydrofluoric (HF) acid is 1 of the strongest and most corrosive acids known.
      Human exposure commonly occurs from occupational releases and can result in
      severe injuries and death. Data from the Agency for Toxic Substances and Disease
      Registry's Hazardous Substances Emergency Events Surveillance (HSEES) system were
      used to conduct a descriptive analysis on the acute health effects of HF acid
      exposure. Of the total HSEES events (n = 49,106), HF acid releases occurred in
      0.3% of events (n = 134). HF acid events were 2 times more likely to involve
      injuries when compared with other acid events and 3 times more likely when
      compared with nonacid events. Employees such as those in trucking services,
      petroleum refining, and chemical manufacturing need to understand the dangers of
      HF acid and should have the appropriate personal protective equipment available
      to prevent exposure.

PMID- 15167400
TI  - How do you counsel law enforcement officers on bodily fluid exposures?

PMID- 15167402
TI  - Antiretroviral adherence in persons with HIV/AIDS and severe mental illness.
AB  - This study identified factors impacting adherence to human immunodeficiency virus
      (HIV) therapies in a sample of 46 persons diagnosed with HIV/acquired immune
      deficiency syndrome and severe mental illness who were receiving care through a
      day care program in Northern California. Comprehensive descriptions of factors
      and circumstances that influence adherence behaviors were obtained through
      critical incident interviews, and a taxonomy of adherence factors was determined.
      A chi2 analysis that examined differences between patient characteristics and
      major adherence factors found that planning was more likely to be reported by
      older persons taking HIV medications over longer periods. Nonwhite persons and
      those living alone were more apt to rely on the use of reminders and cues.
      Persons with bipolar disorder reported substantially more incidents of the impact
      of their symptoms on adherence to HIV therapies than persons with other
      psychiatric diagnoses. The taxonomy of adherence factors provides important
      information for developing relevant adherence education programs and an essential
      foundation for testing compliance interventions.

PMID- 15167403
TI  - Assessing disability in older patients with schizophrenia: results from the
      WHODAS-II.
AB  - The World Health Organization has recently published an instrument to evaluate
      disability, entitled the World Health Organization Disability Assessment Schedule
      Second Version (WHODAS-II). We sought to evaluate its reliability and validity in
      older patients with schizophrenia. We studied 54 outpatients with schizophrenia
      and 22 normal comparison subjects. Besides WHODAS-II, we used standardized rating
      scales to assess positive and negative symptoms, depressive symptoms, cognitive
      functioning, everyday functioning, and quality of well-being. There was high
      internal consistency in WHODAS-II item scores and significant test-retest
      reliability. Patients reported greater disability than normal comparison
      subjects. Among the patients, disability scores were significantly associated
      with severity of depressive symptoms and quality of well-being, but not with
      cognitive performance and everyday functioning. The findings offer strong
      evidence for reliability and some evidence for validity of the WHODAS-II in older
      patients with schizophrenia.

PMID- 15167404
TI  - Relationship between family attitudes and social functioning in schizophrenia: a
      nine-month follow-up prospective study in Spain.
AB  - The objective was to study the relationship between family attitudes and social
      functioning in schizophrenia. A cohort of 80 patients was followed-up for 9
      months after their hospitalization. The relatives' critical attitude and poor
      empathic attitude were measured by means of the Semantic Differential and the
      Questionnaire of Empathy, respectively. Time of useful work and social relations
      of the patients were measured before admission and at the end of follow-up.
      Symptoms, premorbid adjustment, and other course and demographic factors were
      also measured. Significant relationships were found between the relatives' poor
      empathic attitude and the patients' occupational functioning and social
      relations. These associations were maintained after controlling for the effects
      of other prognostic factors. These results suggest that empathy in the relative
      is an independent predictor of social functioning in people with schizophrenia.
      Different attitudinal dimensions of family attitudes might show different
      relationships with the social and clinical outcomes in this disorder.

PMID- 15167405
TI  - Comorbidity of medical illnesses among adults with serious mental illness who are
      receiving community psychiatric services.
AB  - We studied the medical comorbidity among individuals with serious mental illness
      who were receiving community-based psychiatric treatment. A total of 200
      psychiatric outpatients divided between those with schizophrenia and affective
      disorder diagnoses were recruited from samples receiving outpatient care at two
      psychiatric centers. Interviews used questions from national health surveys.
      Logistic regression analyses compared responses from each sample with those of
      matched subsets of individuals from the general population. Both patient groups
      had greater odds of having many medical conditions. The odds of respiratory
      illnesses remained elevated in the patient groups even after controlling for
      smoking, as did the odds of diabetes in the affective disorder group after
      controlling for weight. Persons with serious mental illness who are in outpatient
      care are more likely to have comorbid medical conditions than persons in the
      general population. The odds of diabetes, lung diseases, and liver problems are
      particularly elevated. These findings underscore the need for intensified
      preventive health interventions and medical services for this population.

PMID- 15167406
TI  - Psychological mechanisms mediate psychotic behavior.

PMID- 15167407
TI  - Suicidal behavior and mild traumatic brain injury in major depression.
AB  - Traumatic brain injury (TBI) is associated with psychiatric illness, suicidal
      ideation, suicide attempts, and completed suicide. We investigated the
      relationship between mild TBI and other risk factors for suicidal behavior in
      major depressive episode. We hypothesized that mild TBI would be associated with
      suicidal behavior at least partly because of shared risk factors that contribute
      to the diathesis for suicidal acts. Depressed patients (N = 325) presenting for
      treatment were evaluated for psychopathology, traumatic history, and suicidal
      behavior. Data were analyzed using Student t -test, chi-square statistic, or
      Fisher exact test. A backward stepwise logistic regression model (N = 255)
      examined the relationship between attempter status and variables that differed in
      the TBI and non-TBI patients. Forty-four percent of all subjects reported mild
      TBI. Subjects with TBI were more likely to be male, have a history of substance
      abuse, have cluster B personality disorder, and be more aggressive and hostile
      compared with subjects without TBI. They were also more likely to be suicide
      attempters, although their suicidal behavior was not different from that of
      suicide attempters without TBI. Attempt status was mostly predicted by aggression
      and hostility, but not the presence of TBI. Of note, for males, a history of TBI
      increased the likelihood of being a suicide attempter, whereas the risk was
      elevated for females regardless of TBI history. Our data suggest that suicidal
      behavior and TBI share antecedent risk factors: hostility and aggression. Future
      studies may yield confirmation using a prospective design.

PMID- 15167408
TI  - PTSD reactions and functioning of American Airlines flight attendants in the wake
      of September 11.
AB  - The authors explore the psychological reactions and functional coping responses
      of American Airlines (AA) flight attendants, a unique at-risk group of people in
      the war on terrorism, in the aftermath of the September 11 attacks. Demographic
      characteristics and standardized questionnaires, including the Posttraumatic
      Stress Disorder Checklist and the Psychotherapy Outcome Assessment and Monitoring
      System--Trauma Version, were sent in June 2002 to approximately 26,000 AA flight
      attendants. Of the 2050 respondents, 18.2% reported symptoms consistent with
      probable posttraumatic stress disorder (PTSD). Those living alone were 1.48 times
      more likely to have a probable PTSD diagnosis than those living with someone
      else. Age or years of service as a flight attendant did not predict probable
      PTSD; however, marital status did. Substance abuse was not endorsed as a coping
      strategy. Given the traumatic events experienced by AA flight attendants, and
      persistent threats of future terrorist attacks, these results reveal that
      additional assessment and treatment interventions for stress-related symptoms in
      this population seem warranted.

PMID- 15167409
TI  - Insight in relation to psychosocial adjustment in schizophrenia.
AB  - Insight impairment occurs commonly in patients with schizophrenia, and it can be
      expected that patients with impaired insight may subsequently have poorer
      psychosocial adjustment. The aim of the present study was to measure the
      relationship between insight and psychosocial adjustment in 38 inpatients with a
      diagnosis of DSM-IV schizophrenia. Insight was assessed using the Scale to Assess
      Unawareness of Mental Disorder. A comprehensive set of measures was used to
      assess psychosocial adjustment. No relationship was found between measures of
      psychosocial adjustment and insight. However, a self-rated measure of
      psychosocial adjustment was partially related to insight. Our results suggest
      that patients' insight levels may not be reliable predictors of the patients'
      level of psychosocial adjustment, and that these findings may need to be
      considered in continuous care of psychotic patients, in particular when
      outpatient care needs to be planned.

PMID- 15167410
TI  - Ego-pathology and common symptom factors in schizophrenia.
AB  - The phenomenological construct of ego-pathology in schizophrenia has been widely
      referred to in psychopathological textbooks but was systematically assessed in
      very few empirical studies. This study investigated the association between ego
      pathology (Ego-Pathology Inventory) and common symptom factors (Positive and
      Negative Symptom Scale) in paranoid schizophrenia patients within 3 days after
      admission and after 2 weeks of treatment. The predictive value of ego-pathology
      for short-term treatment outcome was also assessed. A factor analysis of all
      subscale scores revealed a four-factor solution: positive symptoms, negative
      symptoms, and two distinct ego-pathology factors, i.e., general and identity.
      Although the ego-pathology subscale "activity" loaded on the positive symptom
      factor, the other four subscales formed the two ego-pathology factors with no
      high loadings on other factors. High scores on ego-demarcation at admission
      predicted poor treatment outcome after 2 weeks. The findings suggest that ego
      pathology might be used to capture additional and clinically meaningful symptom
      dimensions in schizophrenia.

PMID- 15167414
TI  - Evidence-based management practices: the challenge for nursing.

PMID- 15167417
TI  - The intersection of nursing administration research and health services research:
      stop and look both ways before proceeding!

PMID- 15167418
TI  - Job embeddedness: a theoretical foundation for developing a comprehensive nurse
      retention plan.
AB  - OBJECTIVE: Using a new construct, job embeddedness, from the business management
      literature, this study first examines its value in predicting employee retention
      in a healthcare setting and second, assesses whether the factors that influence
      the retention of nurses are systematically different from those influencing other
      healthcare workers. BACKGROUND: The shortage of skilled healthcare workers makes
      it imperative that healthcare providers develop effective recruitment and
      retention plans. With nursing turnover averaging more than 20% a year and
      competition to hire new nurses fierce, many administrators rightly question
      whether they should develop specialized plans to recruit and retain nurses.
      METHODS: A longitudinal research design was employed to assess the predictive
      validity of the job embeddedness concept. At time 1, surveys were mailed to a
      random sample of 500 employees of a community-based hospital in the Northwest
      region of the United States. The survey assessed personal characteristics, job
      satisfaction, organizational commitment, job embeddedness, job search, perceived
      alternatives, and intent to leave. One year later (time 2) the organization
      provided data regarding voluntary leavers from the hospital. RESULTS: Hospital
      employees returned 232 surveys, yielding a response rate of 46.4 %. The results
      indicate that job embeddedness predicted turnover over and beyond a combination
      of perceived desirability of movement measures (job satisfaction, organizational
      commitment) and perceived ease of movement measures (job alternatives, job
      search). Thus, job embeddedness assesses new and meaningful variance in turnover
      in excess of that predicted by the major variables included in almost all the
      major models of turnover. CONCLUSIONS: The findings suggest that job embeddedness
      is a valuable lens through which to evaluate employee retention in healthcare
      organizations. Further, the levers for influencing retention are substantially
      similar for nurses and other healthcare workers. Implications of these findings
      and recommendations for recruitment and retention policy development are
      presented.

PMID- 15167419
TI  - Nurse staffing and hospital ownership in California.
AB  - OBJECTIVE: The purpose of this study is to describe the relationship between
      nurse staffing and owner type or specific corporate owner in California acute
      care hospitals. BACKGROUND: Little empirical data exist regarding nurse staffing
      as it relates to owner type or specific corporate owner. With minimum staffing
      ratios scheduled to be implemented in January 2004, this study provides baseline
      data for evaluating the impact of minimum staffing ratios in California. METHODS:
      The study design is descriptive and cross-sectional. Data used in this study are
      for short-term general hospitals that reported to the California Office of
      Statewide Health Planning and Development database for fiscal years ending in
      1997 through 1999. Six regression models were estimated using pooled data from
      the 3 years of data. RESULTS: The most consistent significant findings are:
      increased patient days or patient discharges predict increased registered nurse
      (RN) hours; lower RN wages predict increased RN hours; higher technology scores
      predict increased RN hours; and in 1998 there was an across-the-board decrease in
      RN hours. Other significant findings include that for-profit hospitals and for
      profit systems had fewer RN productive hours for medical-surgical nursing, and
      select corporate owners, unrelated to profit status, had consistently fewer RN
      productive hours for medical-surgical nursing. CONCLUSIONS/IMPLICATIONS: For
      profit hospitals and systems behaved differently in the healthcare market
      environment of the late 1990s. Select nonprofit systems were also using
      significantly less RN staffing. Other findings support the implication that as
      technology sophistication increases, there will be a need for increased RN hours
      to manage the advanced technology. This runs counter to the argument that
      increasing technology will decrease the need for RN hours. Finally, as discharges
      go up, the need for RN hours increases.

PMID- 15167420
TI  - Nursing: a stepping stone to future careers.
AB  - OBJECTIVE: To identify the range of positions to which registered nurses moved
      when they left the profession and to explore the perceptions of respondents about
      the skills and experiences gained from performing nursing work. BACKGROUND DATA:
      Many nurses do not remain employed in nursing positions for the duration of their
      working life. This pattern of career change has been seen in many countries,
      including Australia, the United Kingdom, the United States, and Canada. METHODS:
      A mailed questionnaire was completed by respondents who had left nursing. This
      questionnaire covered demographic information, the industry and role in which
      respondents were currently working, ease of adjustment to the current industry
      and role, perceptions of the skills they had gained from nursing, reasons for
      becoming a nurse, and reasons they left nursing. RESULTS: Many respondents moved
      to management positions outside the health industry, and most undertook
      additional study after leaving nursing. In addition, few identified difficulties
      in adapting to non-nursing employment, and most agreed that their nursing skills
      and experiences had assisted them in attaining these positions. CONCLUSIONS: The
      findings are reassuring that employment as a nurse provides invaluable skills for
      a range of employment prospects should an individual wish to change careers.

PMID- 15167421
TI  - Work flow analysis: eliminating non-value-added work.
AB  - OBJECTIVE: To evaluate the impact of implemented work environment changes on
      nursing and support staff roles. BACKGROUND: In 1999, the authors identified key
      drivers of unnecessary work associated with the day-to-day delivery of patient
      care in their institution and implemented changes based on their results.
      METHODS: Both quantitative and qualitative methods were used. Work sampling and
      focus groups were used to evaluate work flow. Activity categories were identified
      and clearly defined by advanced practice nurses. All compiled data were
      subsequently synthesized and cross-checked with the information acquired through
      independent, multidisciplinary validation studies. RESULTS: There were
      significant changes (P <.0001) noted in overall distribution of observed
      activities for nurses and all support staff. CONCLUSIONS: The significant changes
      noted in overall distribution of observed activities reflect the important
      adjustments made in both job descriptions and the environment to eliminate key
      drivers of unnecessary work in the delivery of patient care.

PMID- 15167422
TI  - Defining the heart (and mind) of ECT.

PMID- 15167423
TI  - Changes in heart rate variability in response to treatment with electroconvulsive
      therapy.
AB  - BACKGROUND: Objective methods are needed to determine when to terminate a course
      of electroconvulsive therapy (ECT). Heart rate variability (HRV) has proven
      predictive value for patients with cardiac and neurologic disorders and
      correlates with depression severity and treatment effects. Variable changes in
      HRV after ECT have been reported. METHODS: Holter monitoring was performed before
      and after ECT in 11 patients with depression. Measures of HRV were obtained from
      these recordings and the relationships between HRV and treatment outcome was
      analyzed. Response to ECT was measured by the 24-item Hamilton Rating Scale for
      Depression. RESULTS: Standard deviation of interbeat intervals (SDNN, a measure
      of HRV) increased in subjects who improved with ECT (P < 0.02) but not in those
      who became confused and agitated. Among those patients who acutely responded to
      ECT, SDNN increased (P < 0.05) in subjects with a sustained response but not in
      subjects who relapsed within 3 weeks. SDNN was significantly lower in the rapid
      relapse group at baseline (P < 0.05) and after ECT (P < 0.05) compared with the
      group with a sustained response. CONCLUSIONS: Low baseline HRV is associated with
      rapid relapse of depression after ECT. Both high baseline HRV and increasing HRV
      predict a sustained outcome. Further research is necessary to support these
      findings and to clarify if the serial measurement of HRV during ECT may help to
      determine the optimal number of treatments for each patient.

PMID- 15167424
TI  - No brain perfusion impairment at long-term follow-up in elderly patients treated
      with electroconvulsive therapy for major depression.
AB  - No functional neuroimaging study has previously assessed the long-term effects of
      electroconvulsive therapy (ECT) on brain perfusion. In this study, long-term
      follow-up brain perfusion in elderly patients treated with ECT for severe
      unipolar major depression was assessed. In 14 elderly major depressed patients
      who were ECT remitters, 22 elderly major depressed patients who were
      pharmacological treatment remitters and 25 age- and sex-matched healthy controls,
      a medication-free brain 9mTc-HMPAO-SPECT was performed after a minimum period of
      12 months of euthymia and, in the case of the ECT remitters, at least 12 months
      after the last ECT session. Brain perfusion ratios in major depressed patients
      administered ECT were similar to those in major depressed patients receiving
      pharmacological treatment and in control subjects. This result suggests that
      elderly patients given ECT for severe unipolar major depression do not suffer
      brain perfusion abnormalities at long-term follow-up. Our study adds new evidence
      in favor of the safety of the ECT, particularly in elderly subjects.

PMID- 15167425
TI  - Electroconvulsive therapy practice in Thailand.
AB  - OBJECTIVES: To obtain an overview of electroconvulsive therapy (ECT) practice in
      Thailand. METHODS: Questionnaires were sent to all institutions providing
      psychiatric care; data were collected from September 1, 2001, to August 31, 2002.
      RESULTS: Fifty-three responses were received from 67 institutions (79.1%). ECT is
      available in 26 hospitals. Approximately 6,914 patients received 51,565 ECT
      treatments, of which, 6,469 patients (93.56%) received 48,240 treatments (93.55%)
      in the psychiatric hospitals. The ECT utilization rate was 11.15 patients treated
      per 100,000. Twelve institutions used MECTA (Spectrum or SR1) or Thymatron DGx.
      Bilateral ECT was used exclusively in all institutions. In 2 medical schools, all
      patients received double ECT throughout their treatment courses. Unmodified ECT
      was always used in nine psychiatric hospitals and five general hospitals, and
      occasionally used in 2 university hospitals comprising 94.2% of all ECT usage.
      Patients with schizophrenia most frequently received ECT (74%), followed by mania
      (8%) and major depression (7%). The nurse alone administered ECT in four
      psychiatric hospitals. Although the death rate was estimated at 0.08%, there was
      no ECT-related death during the survey period. Continuation ECT was performed in
      11 and maintenance ECT in 6 institutions. Five institutions had acceptable
      training programs for psychiatry residents but none had training syllabus, 2
      institutions had teaching schedule for medical students. CONCLUSIONS: ECT use in
      Thailand is high. Nearly all ECTs (93.6%) were performed in the psychiatric
      hospital and 94.2% of all treatments were unmodified ECT. Lacking of proper
      training in ECT is evident.

PMID- 15167426
TI  - One-year outcome after response to ECT in middle-aged and elderly patients with
      intractable catatonic schizophrenia.
AB  - BACKGROUND AND OBJECTIVE: ECT is one of the most efficacious treatments for
      catatonic schizophrenia. However, there has been no study on the efficacy of ECT
      in elderly patients with catatonic schizophrenia. Thus, we conducted prospective
      studies on the short-term (phase 1 study) and long-term (phase 2 study) effects
      of acute ECT on intractable catatonic schizophrenia in middle-aged and elderly
      patients. SUBJECTS AND METHODS: The phase 1 study included 11 consecutive
      patients over 45 years of age who fulfilled the DSM-IV criteria for catatonic
      schizophrenia and were referred to Tohoku University Hospital for the first time
      for acute ECT between January 1, 1998, and August 31, 2003, after other
      treatments had failed. We evaluated the clinical response of these patients to
      acute ECT by means of the Brief Psychiatric Rating Scale (BPRS). We also
      evaluated adverse effects of acute ECT. The patient or guardian provided written
      informed consent. Exclusion criterion was a history of dementia or substance
      abuse. Patients were considered clinical responders if they had a BPRS score ;ek
      25 for 1 week after the final ECT session. The phase 2 study included 11
      consecutive patients who responded to acute ECT in the phase 1 study. Patients
      provided written informed consent. Patients' BPRS scores were evaluated weekly
      (18 items, rated 0-6) for 48 weeks or until relapse/recurrence, during which time
      they received pharmacotherapy. Patients were considered clinical "relapsers" if
      they had a BPRS score of at least 37 for 3 consecutive days. Differences in
      clinical characteristics between patients with and without recurrence were
      analyzed statistically by the Mann-Whitney U test. RESULTS: All 11 patients
      completed the phase 1 study, and the acute ECT response rate was 100%. No patient
      experienced a severe adverse cognitive or physical effect during the course of
      acute ECT. All 11 patients also completed the phase 2 study. The mean dose of
      continuation neuroleptics in all 11 cases was 296.8 +/- 277.6 mg (range, 0-982
      mg) (chlorpromazine [CPZ] equivalent). Relapse occurred in 7 cases, and all
      occurred within 6 months. The 1-year recurrence rate was 63.6%. The mean (+/-SD)
      relapse prevention time in the 7 cases was 76.0 +/- 64.7 days (range, 11-163
      days). A significant difference in daily neuroleptic dose before acute ECT was
      found between the patients suffering recurrence and those not suffering
      recurrence (766.7 +/- 521.8 CPZ-equivalent mg with recurrence versus 101.9 +/-
      75.2 CPZ-equivalent mg without recurrence, U = 2.0, P = 0.923). There was a trend
      toward a lower Global Assessment of Functioning (GAF) score just before ECT (7.3
      +/- 4.0 with recurrence versus 16.8 +/- 11.2 without recurrence, U = 4.5, P =
      0.073). CONCLUSIONS: The short-term efficacy of acute ECT for middle-aged and
      elderly patients with intractable catatonic schizophrenia is excellent. However,
      the 1-year recurrence rate, especially the 6-month relapse rate, after response
      to acute ECT is high, despite continuation pharmacotherapy. The need for more
      effective relapse-prevention strategies, such as continuation ECT, is urgent.

PMID- 15167427
TI  - Double-blind placebo controlled study of the effects of etomidate-alfentanil
      anesthesia in electroconvulsive therapy.
AB  - The effect of etomidate and alfentanil on heart rate, systolic arterial pressure,
      diastolic arterial pressure, and mean arterial pressure was compared with
      etomidate and placebo during electroconvulsive therapy (ECT). We also studied the
      influence of alfentanil on seizure duration using both the cuff method and 2-lead
      electroencephalographs on the prevention of myoclonus induction by etomidate, on
      duration of apnea and on postictal agitation after ECT. We enrolled 21
      consecutive patients in a prospective placebo-controlled, within patient blocked
      randomized study. Alfentanil significantly reduced heart rate, diastolic arterial
      pressure, and mean arterial pressure both before and after the stimulus. The
      increase in these variables during the convulsion was not affected, compared with
      placebo. Alfentanil had no effect on seizure duration. However, apnea duration
      was prolonged during the alfentanil sessions as compared with placebo (73
      seconds). Alfentanil did not significantly reduce the occurrence of myoclonus
      after etomidate as compared with placebo, nor did postictal agitation after ECT
      appear more often with alfentanil. Alfentanil could be useful to reduce
      tachycardia and hypertension during ECT in high-risk patients without effects on
      seizure duration. Alfentanil itself has no proconvulsive effect in combination
      with etomidate.

PMID- 15167428
TI  - The first-line use of electroconvulsive therapy in major affective disorders.
AB  - Although electroconvulsive therapy (ECT) has generally been reserved for patients
      refractory to other forms of treatment, its use as a first-line treatment, prior
      to the use of other biologic approaches, has occasionally been mentioned in the
      literature on the treatment of affective disorders and, when indicated, can prove
      rapidly effective and even life saving. The present study retrospectively
      reviewed 27 cases treated over the span of a decade in which ECT was chosen as
      the first treatment of an affective episode. In none of these cases was
      antidepressant medication or other biologic approaches used for the current
      episode. A clinical global rating scale was employed to measure improvement.
      Although the majority of such patients were treated with ECT first based upon the
      severity of their depressive illness, 13 received ECT because of their obtunded
      condition and these patients, initially diagnosed as catatonic on admission, were
      suspected of having a bipolar condition, as revealed on their discharge
      diagnosis. In addition, ECT was recommended preferentially in 4 patients because
      they were pregnant and in another 4 because it had worked well in the past; an
      additional patient received ECT first because of his fragile medical condition.
      Almost all patients recovered and none suffered serious adverse effects. Sample
      case histories are provided along with tentative guidelines for the consideration
      of first-line use of ECT in clinically difficult cases.

PMID- 15167429
TI  - Maintenance ECT for recurrent medication-refractory mania.
AB  - Maintenance electroconvulsive therapy (ECT) can sometimes be the only treatment
      that yields extended periods of euthymia to patients with severe, treatment
      resistant mania. We describe a case of a patient with recurrent and severe mania
      who responded acutely to ECT after failing various medication trials and could
      only maintain euthymia with maintenance ECT.

PMID- 15167430
TI  - Combination propofol-alfentanil anesthesia for electroconvulsive therapy in
      patients receiving monoamine oxidase inhibitors.
AB  - Two patients who had failed outpatient treatment of depression were given
      electroconvulsive therapy while simultaneously being treated with monoamine
      oxidase inhibitors. Both were administered propofol-alfentanil anesthesia without
      complications.

PMID- 15167431
TI  - Successful use of left-unilateral electroconvulsive therapy in a right-handed
      male.
AB  - This case report details the use of left-unilateral electroconvulsive therapy
      (ECT) chosen for this right-handed male for medical reasons outlined in the
      article. Continuation/maintenance ECT was extended for approximately 1 year from
      the beginning of Index ECT. He responded well to the index series and continued
      to respond to the follow-up ECT. His Hamilton Depression Rating scores were close
      to remission 4 weeks after the last ECT. His Mini-Mental Status Examination
      scores were essentially unchanged comparing pre-ECT and post-ECT scores. The
      literature on left-unilateral ECT is reviewed. Earlier reports reported more
      negative cognitive effects with left-unilateral ECT compared with right
      unilateral ECT. The most recent series indicated efficacy for both right and left
      unilateral ECT but with faster improvement, especially from the third to sixth
      ECT for the left-unilateral procedure. There is some support for using left
      unilateral ECT because it appears to have less negative cognitive effect than
      bilateral ECT. This case supports the efficacy of left-unilateral ECT without
      adverse cognitive changes.

PMID- 15167432
TI  - Patient education by electroconvulsive therapy-experienced volunteer.
AB  - By diminishing the patient's attention, concentration, motivation, and
      decisiveness, melancholic depression makes the process of informed consent for
      electroconvulsive therapy more difficult. With such interference, obtaining
      informed consent can be a slow and lengthy process, despite the use of patient
      brochures, videotape programs, and heartfelt educational discussions. A case is
      presented of an impasse in the informed consent process despite protracted and
      lengthy efforts, with lengthened hospital stay. The impasse continued until a
      volunteer discussed his own electroconvulsive therapy experiences with the
      patient. The use of an experienced volunteer with good interpersonal and
      communication skills can help avoid lengthening hospital stay to obtain informed
      consent, especially for patients with melancholic depression.

PMID- 15167433
TI  - Short seizures in continuation electroconvulsive therapy: an indication for
      remifentanil anesthesia?

PMID- 15167434
TI  - Nonconvulsive status epilepticus and electroconvulsive therapy.

PMID- 15167435
TI  - Hypothesis: obesity and the insulin resistance syndrome play a major role in end
      stage renal failure attributed to hypertension and labelled 'hypertensive
      nephrosclerosis'.
AB  - About a third of new cases of renal failure in USA are attributed to hypertension
      despite controversy about the frequency and pathology of so called hypertensive
      nephrosclerosis. In spite of good documentation that obesity causes renal failure
      and in spite of the global epidemic of obesity this diagnosis does not feature on
      most renal failure registries. New documentation that progressive renal failure
      in hypertension is linked to insulin resistance and analysis of NHANES III data
      which shows a strong positive significant dose-response relationship between
      insulin resistance and chronic kidney disease strengthen the view that so called
      hypertensive nephrosclerosis may be linked more closely to obesity and insulin
      resistance than to blood pressure. The pathology of the kidney in hypertension
      has changed. Studies 50 years ago did not show segmental glomerulosclerosis,
      which has recently been shown to be the key lesion in hypertensive
      nephrosclerosis. Recent documentation that this is a major mechanism of
      progression in hypertension together with the fact that similar segmental
      glomerulosclerosis is the key lesion in obesity and the metabolic syndrome
      suggests that these factors are more important than hypertension in renal failure
      attributed to hypertensive nephrosclerosis.

PMID- 15167437
TI  - Self blood pressure measurement at home: how many times?

PMID- 15167436
TI  - Carbon monoxide and hypertension.
AB  - The enzymatic action of heme oxygenase yields carbon monoxide, biliverdin and
      iron. Carbon monoxide is implicated in many physiological processes, including
      the regulation of vascular tissue contractility and apoptosis. By stimulating the
      soluble guanylyl cyclase (sGC)/cGMP pathway and activating K channels in vascular
      smooth muscle cells (SMCs), carbon monoxide relaxes vascular tissues under
      physiological conditions. Altered metabolism and functions of carbon monoxide
      have been linked to the pathogenesis and maintenance of hypertension. The
      expression and activity of heme oxygenase-1, sGC and cGMP in vascular SMCs are
      associated with different stages of development of hypertension in spontaneously
      hypertensive rats (SHRs). The importance of altered heme oxygenase-2 expression
      in vascular tissues in hypertension remains unclear. Increased vascular
      contractility, unbalanced cellular apoptosis and proliferation in the vascular
      wall, increased oxidative stress, and the altered interaction of carbon monoxide
      and nitric oxide are among the consequences of heme oxygenase/carbon monoxide
      system dysfunction in hypertension. Acute application of pharmacological inducers
      to upregulate the expression of heme oxygenase-1 or the use of gene delivery
      method to overexpress heme oxygenase-1 decreases blood pressure in young SHRs and
      other animal models of hypertension. These blood pressure-decreasing effects are
      annulled by metalloporphyrins. In adult SHRs, the heme oxygenase/carbon monoxide
      system appears to be normalized as a compensatory reaction. To date, acute
      manipulation of the expression of heme oxygenase-1 has not been successful in
      decreasing blood pressure in adult SHRs. In conclusion, abnormality of the heme
      oxygenase/carbon monoxide system has a critical role in the pathogenesis of
      hypertension, and novel therapeutic approaches should be pursued to achieve
      selective improvement in the function of this system in hypertension.

PMID- 15167438
TI  - Diogenes in the 2000s: searching for hypertension genes.

PMID- 15167439
TI  - Angiotensin II, platelets and oxidative stress.

PMID- 15167440
TI  - Elevated sympathetic nerve activity: the link between low birth size and adult
      onset metabolic syndrome?

PMID- 15167441
TI  - Hypertension, vasoactive peptides and coagulation factors.

PMID- 15167443
TI  - How many times should blood pressure be measured at home for better prediction of
      stroke risk? Ten-year follow-up results from the Ohasama study.
AB  - OBJECTIVE: To determine the optimum number of blood pressure self-measurements
      taken at home (home blood pressure) in relation to their predictive value for
      stroke risk. METHODS: We obtained more than 14 measurements of home blood
      pressure from 1491 people aged >or=40 years without a history of stroke in the
      general population in Japan, and followed them up after a mean period of 10.6
      years. The prognostic significance of blood pressure for stroke risk was examined
      using the Cox proportional hazards regression model, which was adjusted for
      possible confounding factors. RESULTS: The predictive value of home blood
      pressure increased progressively with the number of measurements, showing the
      highest predictive value with the average of whole measurements (mean = 25
      measurements, 35% increase in the risk of stroke per 10 mmHg elevation in blood
      pressure). The initial home blood pressure values (one measurement) showed a
      significantly greater relation with stroke risk than conventional blood pressure
      values (mean of two measurements) (19/8% increase in the risk of stroke per 10
      mmHg elevation in initial home/conventional systolic blood pressure values,
      respectively). CONCLUSIONS: There was no threshold for the number of home blood
      pressure measurements within the range of 1-14 measurements for increasing the
      predictive power of stroke risk, suggesting that as many measurements as
      possible, preferably more than 14 measurements, is recommended for better
      prediction of stroke risk. It should be emphasized that home blood pressure has a
      stronger predictive power than does conventional blood pressure, even for a lower
      number of measurements.

PMID- 15167442
TI  - Hypertension management and control among English adults aged 65 years and older
      in 2000 and 2001.
AB  - OBJECTIVE: To describe blood pressures, and hypertension and its management among
      older people. DESIGN: Two combined annual cross-sectional surveys. SETTING:
      England 2000 and 2001. PARTICIPANTS: Nationally-representative sample of 3513 non
      institutionalized people aged more than 64 years (elderly). MAIN OUTCOME
      MEASURES: (1). Use of antihypertensive agents, and hypertension according to two
      definitions: receiving blood pressure decreasing treatment, or either: systolic
      blood pressure > or= 160 mmHg or diastolic blood pressure > or= 90 mmHg (old); or
      systolic blood pressure > or= 140 mmHg or diastolic blood pressure > or=90 mmHg
      (new). (2). Rates of treatment and control (old: < 160/90 mmHg; new: < 140/85
      mmHg). (3). Isolated systolic hypertension stage 1 (systolic blood pressure > or=
      140-159 mmHg and diastolic blood pressure < 90 mmHg), or stage 2 (systolic blood
      pressure > or= 160 mmHg and diastolic blood pressure < 90 mmHg). RESULTS: In
      2000/2001, 62 and 81% of elderly adults were hypertensive according to the old
      and new definitions, respectively. Among those with hypertension (new definition)
      treatment and control rates were 56 and 19% (control rates among those treated
      were 36% in men and 30% in women). Of those treated, 54% were receiving one drug,
      35% were receiving two, and 10% were receiving three or more drugs. Among
      untreated hypertensive individuals, 23% had increased systolic and diastolic
      pressures, 76% had isolated systolic hypertension and 1% had isolated diastolic
      hypertension. CONCLUSIONS: These data suggest that, according to current
      guidelines more than 67% of older English adults should receive antihypertensive
      medication. To pre-empt this situation, population-based strategies to reduce the
      current rate of increase in blood pressure throughout adult life should be
      urgently implemented. Only then will the current epidemic of hypertension among
      the elderly, with the huge cost associated with its management and adverse
      cardiovascular sequelae, be averted.

PMID- 15167444
TI  - Reproducibility of intra-arterial ambulatory blood pressure: effects of physical
      activity and posture.
AB  - OBJECTIVE: To examine the effects of physical activity, body posture and sleep
      quality on the reproducibility of continuous ambulatory blood pressure
      monitoring. METHODS: Measurements were performed in 35 subjects (18 hypertensive,
      11 male), mean +/- standard deviation age 49 +/- 13 years. Blood pressure (BP)
      was measured in the brachial artery, and beat-to-beat values of systolic blood
      pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure and heart
      rate (HR) were computed. Physical activity and posture were continuously measured
      with five accelerometers. Subjective quality of sleep was assessed with a
      questionnaire. Reproducibility was expressed as an intraclass correlation
      coefficient and as the standard deviation of the within-subject differences.
      RESULTS: Posture and activity significantly influenced BP and HR. From lying to
      sitting, the SBP, DBP and HR increased 6 mmHg, 8 mmHg and 8 beats/min,
      respectively. From sitting to standing these respective increases were 4 mmHg, 2
      mmHg and 13 beats/min. A further rise in activity (from standing to moving
      generally or walking) increased the SBP by 7 mmHg and the HR by 7 beats/min, and
      decreased the DBP by 8 mmHg. For daytime SBP, DBP and HR, the intraclass
      correlation coefficient (standard deviation of the within-subject differences)
      values were 0.93 (7.2 mmHg), 0.94 (3.8 mmHg) and 0.90 (4.1 beats/min). For night
      time these respective values were 0.98 (4.4 mmHg), 0.97 (2.5 mmHg) and 0.96 (2.2
      beats/min). Correction for physical activity level and posture hardly improved
      the reproducibility of daytime BP and HR. Reproducibility of night-time BP and HR
      was not improved by correction for physical activity, supine position or self
      reported sleep quality. CONCLUSIONS: Within-subject differences between
      ambulatory BP recordings cannot be explained by differences in physical activity
      and body posture.

PMID- 15167445
TI  - Blood pressure surge on rising.
AB  - OBJECTIVES: Since cardiovascular complications tend to occur more often in the
      morning, it is tempting to link this to the surge in blood pressure (BP) on
      rising. Our objective was to measure BP and heart rate (HR) on rising and compare
      values with those recorded immediately beforehand and seek variables related to
      marked changes in the two parameters in a cohort of initially untreated
      hypertensives. METHODS: The 24-h ambulatory BP measurement along with an accurate
      measurement of the BP on rising (either manually or automatically from the device
      coupled with a position sensor) was obtained in untreated hypertensives. Left
      ventricular mass was measured with echocardiography at baseline. Patients were
      then treated and followed by their general physician and news was obtained at
      regular intervals. RESULTS: A total of 507 patients with adequate recordings were
      included. Rising led to a mean increase of 14 mmHg in systolic blood pressure
      (SBP) and a 13 beats per minute (bpm) increase in HR. This elevation in BP on
      rising in the morning differed from the alteration in BP on normal changes in
      position. It was associated with left ventricular hypertrophy at baseline and an
      increased risk of future cardiovascular complications. CONCLUSIONS: Our study
      confirms the surge in BP on rising in the morning. This elevation in BP is
      accompanied by an acceleration in cardiac rhythm with no significant correlation
      between the two parameters. The increase in BP on rising was linked with the
      overall variability in BP, but was independent of the mean BP over 24 h. It was
      associated with an increased risk of cardiovascular complications independently
      of age and average 24-h SBP.

PMID- 15167446
TI  - Genetic analysis of 22 candidate genes for hypertension in the Japanese
      population.
AB  - OBJECTIVE: We performed association studies between 118 single-nucleotide
      polymorphisms (SNPs) of 22 candidate genes (or gene family) and hypertension in a
      Japanese population. DESIGN AND PARTICIPANTS: The study population consisted of
      1880 subjects representing the general population in Japan, recruited from the
      Suita study. The candidate genes were selected based on their functions,
      including insulin resistance (APM1, CD36, HSD11B1), oxidative stress (CYBA, GPX1,
      GSTMs), steroid hormone (ESR1, ESR2, HSD11B2), renal functions (PTGS2, KLK1,
      NPHS1, NPHS2, SGK, SLC12A1, PTGES), and others related to cardiovascular
      physiology (GJA4, NOS1, NTRK3, P2RX4, SPP1, ALDH2). RESULTS: Multiple logistic
      analyses, with age and body mass index as covariates, indicated that 13 SNPs
      (eight genes), six SNPs (four genes) and 11 SNPs (four genes) were associated
      with hypertension (P < 0.05) in the total, male, and female populations,
      respectively. PTGS2 seems to be a promising candidate gene for hypertension in
      men. GSTM3 and SLC12A1 seem to be promising candidate genes for hypertension in
      women. Especially, a polymorphism in SLC12A1 was significantly associated with
      hypertension in women even after correction by the Bonferroni method (corrected P
      = 0.0236). Multiple logistic analyses, with age and body mass index as
      covariates, indicated that the prevalence of hypertension in females was
      significantly higher in subjects with the CC genotype than in those with the TT +
      TC genotypes (P < 0.0001, odds ratio = 1.967, 95% confidence interval = 1.430
      2.712). CONCLUSION: Although the present results should be replicated in other
      study populations for confirmation, the present results suggest that SLC12A1 may
      contribute to hypertension in Japanese women.

PMID- 15167447
TI  - Sex-dependent association of blood pressure with oestrogen receptor genes ERalpha
      and ERbeta.
AB  - BACKGROUND: There is mounting physiological evidence for an important role of the
      oestrogen receptors, ERalpha and ERbeta, in vasodilatation and the response to
      vascular injury. In addition, genetic studies have suggested that the genes
      encoding these receptors may be involved in the genetic regulation of blood
      pressure. The existence of such sex steroid-related genes may help to explain the
      observed sex differences in blood pressure. OBJECTIVE: To investigate the role of
      the oestrogen receptor genes (ERalpha and ERbeta) in blood pressure variation in
      women and in men. DESIGN: We performed a genetic association study of the
      oestrogen receptor genes in 718 unrelated healthy white individuals (386 men and
      332 women) from the parental generation of the Victorian Family Heart Study, a
      general population survey of cardiovascular risk. METHODS: Participants were
      genotyped for single nucleotide polymorphisms (SNPs) in ERalpha and ERbeta, and
      blood pressure phenotypes were compared between genotype groups by analysis of
      variance. RESULTS: When genotype groups were compared, men inheriting the 'a'
      allele of the ERalpha SNP had significantly higher systolic blood pressure than
      men with other genotypes [127.7 +/-14.3 mmHg (mean +/- SD) compared with 132.4 +/
      16.1 mmHg; P = 0.014)]. In addition, men inheriting the 'b' allele of the ERbeta
      SNP had significantly higher diastolic blood pressure than men with other
      genotypes (81.4 +/-8.1 mmHg compared with 84.4 +/- 9.6 mmHg; P = 0.004). No
      significant associations between the oestrogen receptor genes and blood pressure
      were detected in women. DISCUSSION: These results suggest that ERalpha and ERbeta
      may be involved in the genetic regulation of blood pressure in men, that the two
      genes may have different roles, and that these genes may contribute to the
      differences in blood pressures between the sexes.

PMID- 15167448
TI  - High-sensitivity C-reactive protein affects central haemodynamics and
      augmentation index in apparently healthy persons.
AB  - OBJECTIVE: Among apparently healthy women and men, elevated levels of high
      sensitivity C-reactive protein (hsCRP) predict the risk of cardiovascular events
      and may be useful for detecting subclinical atherosclerosis. The aim of this
      study was to investigate the associations between inflammatory markers,
      augmentation index (AIx), central pulse pressure and central systolic blood
      pressure in apparently healthy subjects. DESIGN AND SETTINGS: An observational
      study conducted at a university teaching hospital. METHODS AND RESULTS:
      Apparently healthy subjects (n = 158; 75 males, 83 females) passed a complete
      history and physical examination, blood tests and pulse wave analysis.AIx was
      significantly higher in patients with hsCRP levels above 1 mg/l (24.5 +/-9.9
      versus 18.1+/-12.6%, P < 0.001). Central pulse pressure and central systolic
      blood pressure were significantly higher in the group with hsCRP levels above 1
      mg/l. No differences between groups were shown for peripheral pulse pressure,
      peripheral blood pressures and estimated aortic pulse wave velocity. In multiple
      regression analysis, AIx correlated positively with age, female gender, short
      stature, mean arterial pressure, hsCRP (P = 0.026) and white blood cell count (P
      = 0.01), and negatively with heart rate. CONCLUSIONS: This study shows that
      plasma levels of hsCRP are positively correlated with AIx, central pulse pressure
      and central systolic blood pressure. Apparently healthy subjects with increased
      inflammatory markers have increased systemic arterial stiffness, which might
      reflect early atherosclerotic changes. Our results suggest that hsCRP and non
      invasively measured arterial stiffness could serve as additional tools, beside
      conventional cardiovascular risk factors, for assessment of global arterial risk
      and preclinical atherosclerotic changes in arteries.

PMID- 15167449
TI  - Angiotensin II and endothelin-1 regulate MAP kinases through different redox
      dependent mechanisms in human vascular smooth muscle cells.
AB  - OBJECTIVE: The role of reactive oxygen species (ROS) in mitogen-activated protein
      kinase (MAPK) signaling by angiotensin (Ang) II and endothelin-1 (ET-1) in human
      vascular smooth muscle cells (VSMC) was investigated. DESIGN: VSMCs were derived
      from resistance arteries from healthy subjects. MAPK activity was assessed using
      phospho-specific antibodies. ROS generation was measured by CMH2DCFDA
      fluorescence and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      activity by lucigenin chemiluminescence. RESULTS: Ang II and ET-1 increased MAPK
      phosphorylation (P < 0.01). Pre-treatment with Tiron and Tempol, *O2 scavengers,
      attenuated agonist-stimulated phosphorylation of p38MAPK, c-Jun N-terminal
      kinases (JNK) and ERK5, but not of ERK1/2 (extracellular signal-regulated
      kinases). Apocynin and diphenylene iodinium (DPI), NAD(P)H oxidase inhibitors,
      decreased Ang II-induced responses 60-70%. ET-1-mediated MAPK phosphorylation was
      unaffected by apocynin but was reduced (> 50%) by thenoyltrifluoroacetone (TIFT)
      and carboxyl cyanide-m-chlorophenylhydrazone (CCCP), mitochondrial inhibitors.
      Allopurinol and N-nitro-l-arginine methyl ester (l-NAME), xanthine oxidase and
      nitric oxide synthase (NOS) inhibitors, respectively, did not influence MAPK
      activation. Intracellular ROS generation, was increased by Ang II and ET-1 (P <
      0.01). DPI inhibited Ang II- but not ET-1-mediated ROS production. Expression of
      p22phox and p47phox and activation of NAD(P)H oxidase were increased by Ang II
      but not by ET-1. CCCP and TIFT significantly attenuated ET-1-mediated ROS
      formation (P < 0.05), without influencing Ang II effects. CONCLUSIONS: Ang II
      activates p38MAPK, JNK and ERK5 primarily through NAD(P)H oxidase-generated ROS.
      ET-1 stimulates these kinases via redox-sensitive processes that involve
      mitochondrial-derived ROS. These data suggest that redox-dependent activation of
      MAPKs by Ang II and ET-1 occur through distinct ROS-generating systems that could
      contribute to differential signaling by these agonists in VSMCs.

PMID- 15167450
TI  - Enhanced platelet release of superoxide anion in systemic hypertension: role of
      AT1 receptors.
AB  - BACKGROUND: Enhanced oxidative stress has been observed in hypertension, but the
      underlying mechanism has not been fully clarified. OBJECTIVE: To study the
      relationship between oxygen free radicals and hypertension, using platelets as a
      tool to measure the cellular production of superoxide anion (O2). DESIGN: Forty
      patients with hypertension were allocated randomly to groups to receive either
      irbesartan, an inhibitor of angiotensin II type 1 (AT1) receptors (n = 20), or a
      diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced
      production of O2 by platelets was studied before and after 4 weeks of treatment.
      Forty sex- and age-matched healthy individuals were studied as controls. METHODS:
      Platelet-produced O2 was measured using lucigenin chemiluminescence and
      hydroethidine cytofluorimetric analysis. RESULTS: Compared with healthy
      individuals, patients with hypertension showed a greater production of O2 by
      platelets (P < 0.001); there was no correlation between blood pressure and
      platelet O2 production. After treatment, no changes in platelet O2 formation were
      observed in patients receiving hydrochlorothiazide; conversely, those treated
      with irbesartan showed a significant (P < 0.001) decrease in platelet O2
      production. At the end of the treatment, no differences in blood pressures were
      observed between the two groups. In-vitro incubation of platelets with
      angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose
      dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of
      NADPH oxidase. CONCLUSION: Patients with hypertension showed an enhanced
      formation of O2 in platelets that was not dependent on blood pressure but could
      be mediated by AT1 receptors via NADPH oxidase activation.

PMID- 15167451
TI  - Low birth size and final height predict high sympathetic nerve activity in
      adulthood.
AB  - OBJECTIVE: Being born small for gestational age (SGA) is associated with insulin
      resistance, hypertension and increased cardiovascular morbidity/mortality in
      adulthood. Sympathetic nerve hyperactivity is a well-known risk factor for
      cardiovascular disease mortality and is proposed to link insulin resistance with
      hypertension. The objective of this study was to test the hypothesis that
      sympathetic nerve activity is altered in individuals born SGA. DESIGN: A cross
      sectional, comparative study of 20 healthy adults (21-25 years old) born SGA
      (birth weight < -2SD score for healthy newborns) with normal and short stature,
      and 12 age, gender and body mass index matched individuals, born appropriate for
      gestational age (AGA) with normal stature. METHODS: Direct recordings of resting
      sympathetic nerve activity to the muscle vascular bed (MSA) were obtained from
      the peroneal nerve posterior to the fibular head. Heart rate, respiration and
      blood pressure were recorded during the microneurographic session. RESULTS: MSA
      was increased in both groups of young adults born SGA as compared to those born
      AGA (P < 0.05 and P < 0.005, respectively). In the combined study group MSA was
      inversely correlated to birth weight, length (r = -0.59, P < 0.001 and r = -0.69,
      P < 0.0005, respectively) and final adult height (r = -0.58; P < 0.001).
      CONCLUSIONS: Being born SGA and achieving a short final height is associated with
      increased sympathetic nerve traffic. We suggest that the increase in sympathetic
      nerve traffic in young adults born SGA with normal and short stature may be the
      link between low birth size, hypertension and cardiovascular morbidity later in
      life.

PMID- 15167452
TI  - Restoration of baroreflex function by ketanserin is not blood pressure dependent
      in conscious freely moving rats.
AB  - OBJECTIVE: Since the end of the 1980s, the pathological importance of baroreflex
      function has attracted the attention of many investigators. In our previous
      studies, it was found that ketanserin lowered blood pressure (BP), decreased BP
      variability and enhanced baroreflex sensitivity (BRS). The present work was
      designed to test the hypothesis that the restoration of BRS by ketanserin is not
      dependent on BP level in conscious rats. DESIGN AND METHODS: Spontaneously
      hypertensive rats (SHR) aged 8-12 months were used. Blood pressure was recorded
      for 60 min and BRS was determined separately before and after intragastric
      administration of ketanserin, with four doses. In a second experiment, 10-week
      old Sprague-Dawley rats were used for preparing a myocardial infarction (MI)
      model by ligating the coronary artery. MI rats were treated with ketanserin for 5
      weeks, with two doses. At the end of the treatment, BP and BRS of the MI rats
      were studied in conscious state. In addition, the effects of ketanserin on BRS in
      Sprague-Dawley rats with normal BRS and the effects of prazosin and ritanserin on
      BRS in SHR were also observed. RESULTS: It was found that ketanserin
      significantly decreased BP and improved BRS in the conscious SHR. The decrease in
      BP was dose-dependent but the improvement of BRS was not. At the smallest dose
      (0.3 mg/kg), ketanserin did not lower BP but enhanced BRS. In MI rats, the
      treatment with ketanserin did not significantly decrease BP, but it improved BRS
      at both doses administered (0.6 and 10 mg/kg). Ketanserin [3 and 10 mg/kg,
      intragastric (i.g.)] did not affect BRS in SD rats with normal BRS. Prazosin and
      ritanserin did not enhance BRS in SHR when administered intravenously. Ritanserin
      markedly and prazosin slightly enhanced BRS in SHR following
      intracerebroventricular administration. CONCLUSION: The restoration of baroreflex
      function by ketanserin is not BP dependent and this effect is mediated by central
      5-HT2A receptor.

PMID- 15167453
TI  - Role of bradykinin B2-receptor in the sympathoadrenal effects of 'new pressor
      protein' related to human blood coagulation factor XII fragment.
AB  - BACKGROUND: Human plasma new pressor protein (NPP) increases blood pressure,
      heart rate and plasma adrenal medullary catecholamines in bioassay rats - all
      potentiated by angiotensin-converting enzyme (ACE) inhibition. High plasma NPP
      activity has been found in haemodialysis patients with hypertension. OBJECTIVE:
      To investigate whether the bradykinin B2-receptor mediates the effects of NPP.
      METHODS AND RESULTS: Male Wistar bioassay rats were anaesthetized with inactin,
      ganglion blocked with pentolinium and injected intravenously (i.v.) with human
      NPP (20 microl plasma equivalent) or bradykinin (100 ng/kg). Both NPP and
      bradykinin increased systolic (SBP) and diastolic (DBP) blood pressures, heart
      rate and plasma adrenaline and noradrenaline concentrations. All these responses
      were potentiated by the ACE inhibitor, captopril (10 mg/kg i.v.), but not by
      antagonism of the angiotensin II type 1 receptor with losartan (10 mg/kg i.v.).
      Administration of the bradykinin B2-receptor antagonist, HOE-140 (20 microg/kg
      i.v.), significantly attenuated the peak NPP responses as follows: SBP from 58 +/
      3 to 40 +/- 4 mmHg (decrease of 30%; P < 0.05); DBP from 22 +/- 4 to 10 +/- 1
      mmHg (decrease of 55%; P < 0.05); heart rate from 124 +/- 8 to 28 +/-6 beats/min
      (decrease of 77%; P < 0.05); plasma adrenaline from 14297 +/- 2477 to 3318 +/-
      1105 pg/ml (decrease of 77%; P < 0.05) and noradrenaline from 505 +/- 66 to 77 +/
      29 pg/ml (decrease of 85%; P < 0.05). CONCLUSIONS: The haemodynamic and
      sympathoadrenal effects of NPP involve substantial mediation by the bradykinin B2
      receptor, in addition to other mechanisms.

PMID- 15167454
TI  - The cardiovascular effects of nitric oxide and carbon monoxide in the nucleus
      tractus solitarii of rats.
AB  - OBJECTIVE: Nitric oxide (NO) and carbon monoxide (CO) are endogenously
      synthesized gaseous molecules that act as neurotransmitters in both central and
      peripheral nervous systems. Previously, we have shown the involvement of NO and
      CO in central cardiovascular regulation and baroreflex modulation. In this study
      we investigated the possible interaction of NO and CO in the nucleus tractus
      solitarii (NTS) on cardiovascular effects in rats. DESIGN AND METHODS: Male
      Sprague-Dawley rats were anesthetized with urethane, and mean blood pressure
      (MBP) and heart rate (HR) were monitored intra-arterially. l-Arginine (3.3 nmol),
      the precursor of NO, or hematin (1 nmol), a heme molecule cleaved by heme
      oxygenase (HO) to yield CO, were microinjected unilaterally into the NTS.
      Cardiovascular effects were evaluated before and after microinjection of the HO
      inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG: 1 nmol) or the NO
      synthase (NOS) inhibitors N -monomethyl-l-arginine (l-NMMA: 10, 33 and 100 nmol)
      and N-nitro-l-arginine methyl ester (l-NAME: 10, 33 and 100 nmol). RESULTS:
      Unilateral microinjection of l-arginine or hematin into the NTS produced
      decreases in blood pressure and heart rate. These cardiovascular effects of both
      l-arginine and hematin were attenuated by prior administration of the NOS
      inhibitors l-NMMA or l-NAME in a dose-dependent manner. However, prior
      administration of ZnDPBG attenuated only the cardiovascular effects of hematin
      but not l-arginine. CONCLUSIONS: These results demonstrated that the HO/CO
      pathway might couple to the activation of NOS via the liberation of NO, to
      participate in central regulation of cardiovascular function. They also suggested
      a possible interaction between the NO/NOS and CO/HO systems in the NTS of rats.

PMID- 15167455
TI  - Cardiac gene expression of natriuretic substances is altered in streptozotocin
      induced diabetes during angiotensin II-induced pressure overload.
AB  - OBJECTIVE: To gain insight into the cardiac adaptive mechanisms in diabetes, we
      studied whether angiotensin II (Ang II) alters expression of the atrial
      natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and adrenomedullin
      (AM) genes in the left ventricle of the diabetic rat heart. METHODS: Diabetes was
      induced by streptozotocin (STZ; 60 mg/kg body weight intravenously). During the
      last 24 h of 2.5 or 7 weeks of treatment of male Wistar rats with STZ or vehicle,
      Ang II (33 microg/kg per h) was administered via osmotic minipumps. RESULTS:
      Diabetes was associated with an increased left ventricular weight to body weight
      (LV/BW) ratio, an index of left ventricular hypertrophy, at week 7 but not at
      week 2.5, and with increased ANP mRNA content at 2.5 weeks, but not with altered
      expression of the AM and BNP genes. Mean arterial pressure and LV/BW ratio were
      increased by Ang II in all groups except in the 7-week diabetic group. Levels of
      ANP mRNA were increased fourfold (P < 0.001) and threefold (P < 0.05) by Ang II
      at 2.5 and 7 weeks in control animals, respectively, and 11-fold (P < 0.001) and
      sevenfold (P < 0.001) at 2.5 and 7 weeks in diabetic animals, respectively. Ang
      II increased ventricular concentrations of BNP mRNA in control and diabetic
      animals at 2.5 weeks (1.3-fold, P < 0.001; and 1.6-fold, P < 0.001) and at 7
      weeks (1.3-fold, P < 0.05; and 1.8-fold, P < 0.001), respectively. Left
      ventricular levels of adrenomedullin mRNA were increased by treatment with Ang II
      for 24 h in 2.5-week diabetic animals. CONCLUSION: Ang II markedly increased the
      levels of natriuretic peptide mRNAs in the left ventricle of normal and diabetic
      rat hearts, whereas it increased adrenomedullin mRNA levels only in 2.5-week
      diabetic rats and failed to cause hypertension in 7-week diabetic rats. Left
      ventricular levels of ANP and BNP mRNA were increased by Ang II in diabetic
      animals more than the additive effects of diabetes and Ang II alone, showing that
      Ang II induced an amplified response with respect to cardiac concentrations of
      ANP and BNP in diabetes.

PMID- 15167456
TI  - Absolute and relative changes in carotid intima-media thickness and
      atherosclerotic plaques during long-term antihypertensive treatment: further
      results of the European Lacidipine Study on Atherosclerosis (ELSA).
AB  - BACKGROUND: In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4
      year antihypertensive treatment with lacidipine slowed down progression of
      carotid atherosclerosis significantly more than atenolol treatment. To avoid
      bias, the primary outcome was measured blindly at study-end on a randomized
      sequence of scans, but measurements were limited to the four far walls of common
      carotids and bifurcations (CBMmax) and to one of each couple of duplicate scans
      recorded yearly. OBJECTIVES AND METHODS: Secondary outcomes included measurements
      made on all duplicate scans of both near and far walls, not only of common
      carotids and bifurcations, but also of internal carotids (12 walls). These
      measurements were made blindly during the 4-year study, shortly after recording.
      To avoid possible readers' drift or bias, 250 duplicate baseline scans were re
      read at yearly intervals (longitudinal on-line quality control) and a correction
      factor calculated. RESULTS: Measurements during the 4-year study showed a trend
      toward decreased values, with the lacidipine effect significantly greater than
      the atenolol one. A trend toward lower values was also observed in the
      longitudinal quality control of baseline scans. After applying a correction
      factor calculated from this longitudinal control, all measurements no longer
      decreased with time, but significantly increased, with progression being
      significantly smaller in lacidipine than in atenolol patients. Corrected values
      were quite similar to those calculated on measurements carried out at study-end.
      CONCLUSION: The relative benefit of lacidipine over atenolol could be measured
      precisely by reading scans either during the study or at study-end. However,
      absolute treatment-related changes (progression versus regression) cannot safely
      be judged by readings made during a long-term study, unless a longitudinal
      quality control of readings is performed.

PMID- 15167457
TI  - Gender difference in the response to an angiotensin-converting enzyme inhibitor
      and a diuretic in hypertensive patients of African descent.
AB  - BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in
      decreasing blood pressure in African patients is controversial. OBJECTIVE: We
      examined the ambulatory blood pressure (ABP) response to a diuretic and an ACE
      inhibitor in hypertensive patients of East African descent and evaluated the
      individual characteristics that determined treatment efficacy. DESIGN: A single
      blind randomized AB/BA crossover design. SETTING: Hypertensive families of East
      African descent from the general population in the Seychelles. PARTICIPANTS:
      Fifty-two (29 men and 23 women) out of 62 eligible hypertensive patients were
      included.Main outcome measures ABP response to 20 mg lisinopril (LIS) daily and
      25 mg hydrochlorothiazide (HCT) daily given for a 4-week period. Results The
      daytime systolic/diastolic ABP response to HCT was 4.9 [95% confidence interval
      (CI) 1.2-8.6]/3.6 (1.0-6.2) mmHg for men and 12.9 (9.2-16.6)/6.3 (3.7-8.8) mmHg
      for women. With LIS the response was 18.8 (15.0-22.5)/14.6 (12.0-17.1) mmHg for
      men and 12.4 (8.7-16.2)/7.7 (5.1-10.2) mmHg for women. The night-time
      systolic/diastolic response to HCT was 5.0 (0.6-9.4)/2.7 [(-0.4)-5.7] mmHg for
      men and 11.5 (7.1-16.0)/5.7 (2.6-8.8) mmHg for women, and to LIS was 18.7 (14.2
      22.1)/15.4 (12.4-18.5) mmHg for men and 3.5 [(-1.0)-7.9]/2.3 [(-0.8)-5.4] mmHg
      for women. Linear regression analyses showed that gender is an independent
      predictor of the ABP responses to HCT and to LIS. CONCLUSIONS: Hypertensive
      patients of African descent responded better to LIS than to HCT. Men responded
      better to LIS than to HCT and women responded similarly to both drugs.

PMID- 15167459
TI  - Pathogenesis of structural vascular changes in hypertension.

PMID- 15167458
TI  - Reasons for not intensifying antihypertensive treatment (RIAT): a primary care
      antihypertensive intervention study.
AB  - OBJECTIVE: Hypertension is often poorly controlled, despite its importance and
      despite the availability of very effective treatments. An under-recognized
      problem is the failure of consensus guidelines to acknowledge the important
      difference between efficacy in clinical trials and effectiveness in clinical
      practice. The present survey was designed to prospectively assess what is the
      target blood pressure (BP) goal defined by a general practitioner (GP) for an
      individual patient, and what are the reasons for not modifying an
      antihypertensive drug regimen, when pre-defined individual BP goals are not
      achieved. DESIGN: Family practice based, open intervention survey. SUBJECTS:
      Participating GPs enrolled 2621 hypertensive patients. At the first visit each
      physician was required to assess the cardiovascular risk profile of each patient
      and to define individual BP targets. INTERVENTIONS: Treatment was started with
      irbesartan alone or in fixed combination with hydrochlorothiazide. Follow-up
      visits were suggested after 1 month, 2 months and 4 months. Physicians were asked
      to report BP values under the new treatment regimen and to indicate whether in
      their opinion pre-defined BP targets set at baseline were achieved or not and
      whether the antihypertensive regimen was modified or maintained in relation to
      whether target BP was reached or not. MAIN OUTCOME MEASURE: To provide reasons
      for not changing the treatment even though BP goals were missed. RESULTS: Average
      target BP values defined by the physicians at baseline were 138 +/- 8 mmHg for
      systolic and 84 +/- 5 mmHg for diastolic BP. Among GPs, defined target BP values
      did not depend on individual risk stratification, but rather depended on baseline
      BP values. At baseline systolic and diastolic BP averaged 165/97 +/- 17/10 mmHg,
      while at the last visit achieved BP averaged 140/84 +/- 14/8 mmHg. There were
      three main reasons for not intensifying antihypertensive treatment when BP
      targets were not achieved. These reasons were: (1). the assumption that the time
      after starting the new drug was too short to appreciate its full effect (44% at
      first, 14% at last follow-up), (2). that there was a clear improvement or the
      target BP was almost reached (24% at first, 34% at last follow-up) or (3). that
      self-measurements were considered satisfactorily (10% at the last visit).
      CONCLUSIONS: Failure of physicians to follow guidelines is apparently dependent
      on the belief that baseline BP dictates the target, that a clear improvement in
      BP might be sufficient and that the full drug effect may take up to 4 months or
      more to be attained.

PMID- 15167461
TI  - Cardiovascular effects and efficacy of a hemostatic agent in periradicular
      surgery.
AB  - The purpose of this study was to evaluate the hemostatic efficacy and systemic
      cardiovascular effects of CollaCote collagen sponges saturated with 2.25% racemic
      epinephrine during endodontic surgery. A total of 48 patients participated in the
      study. Patients received CollaCote-saline or CollaCote-epinephrine placed in the
      bony crypt, after which hemostatic efficacy was evaluated. Blood pressure and
      pulse rate was recorded before and after administration of the local anesthetic,
      after the application of the test solutions, and before the patient's dismissal.
      Results showed no significant difference in blood pressure or pulse rate between
      the experimental and control groups. In the CollaCote-saline group, five of six
      cases failed to achieve hemorrhage control. In the CollaCote-epinephrine group, 1
      of 42 cases had no hemorrhage control. Two patients had slight but apparent
      intermittent bleeding. Complete hemostasis was achieved in 39 of 42 cases. In
      conclusion, the results suggest that CollaCote collagen sponges saturated with
      2.25% racemic epinephrine provide excellent hemostasis with no evident changes in
      blood pressure or pulse rate.

PMID- 15167462
TI  - Pulp responses to precise thermal stimuli in dentin-sensitive teeth.
AB  - The purpose of this study was to determine whether pulpal responses to cold
      temperatures applied to enamel, using a method that precisely controls the
      intensity of the cold stimulus or measures the response time, could distinguish
      dentin-sensitive teeth from nonsensitive teeth. Eighteen human subjects were
      stimulated with cold temperatures decreasing in 5 degree C intervals (and with
      tetrafluoroethane) on exposed root and enamel of a dentin-sensitive tooth and
      enamel of a contralateral nonsensitive tooth. Pain threshold, intensity of pain,
      time to pain onset, and duration of pain at baseline, 4 h, 8 h, and 1 week were
      measured. Responses to enamel stimulation of sensitive teeth compared with the
      nonsensitive teeth usually were highly correlated and not significantly
      different. The exception was a longer duration of pain in the dentin-sensitive
      teeth (4.62 +/- 0.47 s) compared with nonsensitive teeth (2.92 +/- 0.49 s; p =
      0.016) after enamel stimulation with tetrafluoroethane. Longitudinal studies are
      necessary to determine whether these slight increases in pain duration indicate
      an increased probability of pulpal degeneration or need for dentin protection.

PMID- 15167463
TI  - Morphological measurements of anatomic landmarks in human maxillary and
      mandibular molar pulp chambers.
AB  - The aim of this in vitro study was to measure critical morphology of molar pulp
      chambers. One hundred random human maxillary and mandibular molars (200 teeth in
      total) were used. Each molar was radiographed mesiodistally on a millimeter grid.
      Using a stereomicroscope, the measurements were read to the nearest 0.5 mm.
      Results were as follows (mean, mm): pulp chamber floor to furcation, maxillary =
      3.05 +/- 0.79, mandibular = 2.96 +/- 0.78; pulp chamber ceiling to furcation,
      maxillary = 4.91 +/- 1.06, mandibular = 4.55 +/- 0.91; buccal cusp to furcation,
      maxillary = 11.15 +/- 1.21, mandibular = 10.90 +/- 1.21; buccal cusp to pulp
      chamber floor, maxillary = 8.08 +/- 0.88, mandibular = 7.95 +/- 0.79; buccal cusp
      to pulp chamber ceiling, maxillary = 6.24 +/- 0.88, mandibular = 6.36 +/- 0.93;
      and pulp chamber height, maxillary = 1.88 +/- 0.69, mandibular = 1.57 +/- 0.68.
      The pulp chamber ceiling was at the level of the cementoenamel junction in
      maxillary, 98%, and mandibular, 97% of the specimens. The measurements showing
      the lowest percentage variance were buccal cusp to furcation (approximately 11%)
      and buccal cusp to pulp chamber ceiling (approximately 14%). The measurements
      were similar for both maxillary and mandibular molars.

PMID- 15167464
TI  - Evaluation of the root canal configurations of the mandibular and maxillary
      permanent teeth by gender in the Turkish population.
AB  - A key objective of successful nonsurgical endodontic treatment is obturation of
      the root canal systems. One factor in achieving this goal is the knowledge of
      possible root canal morphologies. Root canal morphology may exhibit variation as
      a result of many factors, including ethnic origin. In this study, 1400 male and
      1400 female extracted mandibular and maxillary permanent teeth were evaluated for
      patterns in root canal morphology. The mandibular and maxillary teeth were
      divided into seven groups of tooth type (e.g. centrals, laterals, canines, first
      premolars, second premolars, first molars, and second molars), subdivided into
      gender, and classified by root canal morphologies. Vertucci's classification was
      taken as a reference during the evaluation. Although a majority of the specimens
      corresponded to this classification scheme, the analysis of this large data set
      revealed 14 additional root canal morphologies.

PMID- 15167465
TI  - Effect of chlorophyllin on normothermic storage of human periodontal ligament
      cells.
AB  - The purpose of the present study was to evaluate whether chlorophyllin could
      serve as an effective constituent of a storage medium to enhance the human
      periodontal ligament (PDL) cell viability. Freshly isolated PDL cells from
      premolars extracted from healthy people were stored at 37 degrees C for 6 h in
      various solutions: F-medium and Hank's balanced salt solution (HBSS),
      supplemented with chlorophyllin. From MTT viability assays, the highest cell
      viability was found in the PDL cells stored in HBSS supplemented with 500 nM
      chlorophyllin, and the chlorophyllin-treated cells showed a dose-dependent
      response to concentration. Additionally, the results from flow cytometry showed
      that 77 to 80% of the PDL cells were in the G0/G1 phases of the cell cycle, which
      suggested that most were in a stable stage. These result showed that HBSS,
      supplemented with chlorophyllin, may be a useful solution for preserving the
      viability of PDL cells.

PMID- 15167466
TI  - Comparative study of apical sealing ability of a new resin-based root canal
      sealer.
AB  - The purpose of this study was to compare the microleakage of two root canal
      sealers, Fibrefill (resin-based sealer) and calciobiotic root canal sealer (CRCS;
      calcium hydroxide-based sealer), with and without the presence of smear layer.
      The model used for the measurement of microleakage was a fluid transport model.
      Sixty human extracted teeth were used in this study. The teeth were divided into
      four groups and treated as follows. In group A, the smear layer was left intact,
      and canals were obturated with gutta-percha and Fibrefill. In group B, the smear
      layer was removed, and canals were obturated with gutta-percha and Fibrefill. In
      group C, the smear layer was left intact, and the canals were obturated with
      gutta-percha and CRCS. In group D, the smear layer was removed, and canals were
      obturated with gutta-percha and CRCS. Microleakage was measured at 7 days, 1
      month, and 2 months. The results showed that the Fibrefill groups with and
      without smear layer leaked significantly less than the CRCS groups at all
      experimental times. No significant difference was found between the groups of
      same materials, but the microleakage values were less when the smear layer was
      removed.

PMID- 15167467
TI  - Evaluation of the influence of smear layer on the apical and coronal sealing
      ability of two sealers.
AB  - The aim of this in vitro study was to determine the effect of the smear layer on
      apical and coronal leakage in root canals obturated with AH26 or RoekoSeal
      sealers. A total of 160 maxillary anterior teeth extracted for periodontal
      reasons were used. The root canals were prepared to a size #7 with ProFile.06
      taper Series 29 rotary instruments in a crown-down manner. Eight groups were
      created by all possible combinations of three factors: smear layer
      (present/absent), leakage assessment (apical/coronal), and sealer used
      (AH26/RoekoSeal). All teeth were obturated using lateral condensation technique
      of gutta-percha. A fluid filtration method was used to test apical or coronal
      leakage. According to the results of this study, the smear (+) groups displayed
      higher apical and coronal leakage than those smear (-) groups for both root canal
      sealers (p < 0.05). There was no statistically significant difference in either
      apical or coronal leakage between RoekoSeal and AH26, regardless of the presence
      or absence of the smear layer (p > 0.05). However, apical leakage was
      significantly higher than coronal leakage for both root canal sealers used in
      this study (p < 0.05). Under the conditions of this study, the results indicate
      that removal of the smear layer has a positive effect in reducing apical and
      coronal leakage for both AH26 and RoekoSeal root canal sealers.

PMID- 15167468
TI  - In vitro study of the torsional properties of new and used ProFile nickel
      titanium rotary files.
AB  - The purpose of this study was to investigate torque and angle of rotation at
      fracture of new and used.06 ProFile instruments. ProFile sizes 15 to 40 were
      tested according to American National Standards Institute/American Dental
      Association Specification #28. Thirty new and used instruments were tested for
      each size. An analysis of variance was used to compare the torque and angle of
      rotation at fracture between new and used instruments. The relationship between
      torque at fracture and size of instrument was determined with a regression
      analysis. The used instruments had significantly lower torque and angle of
      rotation at fracture values compared with the new instruments (p < 0.0001). A
      stronger relationship was found between the size of the instrument and the torque
      at fracture for the new instruments (p < 0.0001) than for the used ones (p <
      0.0001). In conclusion, the repeated use of.06 ProFile instruments significantly
      reduced the torque and angle of rotation at fracture.

PMID- 15167469
TI  - Physical and chemical properties of chlorhexidine and calcium hydroxide
      containing medications.
AB  - This study was performed to evaluate the physicochemical properties (pH, contact
      angle, working time, radio-opacity, and viscosity) of chlorhexidine (CHX) and
      calcium hydroxide-containing medications in gel form in different concentrations.
      The pH value was assessed with a pH meter. The contact angle was measured with a
      goniometer. The radio-opacity and working time measurements were taken in
      accordance with the standards of the International Organization for
      Standardization. The viscosity was evaluated using a Brookfield RVDV viscometer.
      The results showed that CHX did not affect the pH, radio-opacity, and working
      time of the calcium hydroxide-containing medications (p < 0.05). However, adding
      CHX lowered the contact angle and increased the viscosity of calcium hydroxide
      significantly. This research showed that CHX in different concentrations and in
      combination with calcium hydroxide has satisfactory physicochemical properties to
      be used as an intracanal medication.

PMID- 15167470
TI  - Apical extrusion of thermoplasticized obturating material in canals instrumented
      with Profile 0.06 or Profile GT.
AB  - The purpose of this in vitro study was to compare the extrusion of
      thermoplacticized gutta-percha in teeth instrumented with Profile 0.06 or Profile
      GT, and obturated with Thermafil Plus and Thermafil GT, respectively. A total of
      120, extracted, human maxillary central incisors were divided into four equal
      groups. Group 1 was instrumented with Profile 0.06 and obturated with Thermafil
      Plus. Group 2 was instrumented with Profile 0.06 and obturated using warm
      vertical condensation (negative control). Group 3 was instrumented with Profile
      GT and obturated with Thermafil GT. Group 4 was instrumented with Profile GT and
      obturated like Group 2 (negative control). Extrusion was graded as present or
      absent. Results found 9 of 30 extruded for group 1, 1 of 30 for group 2, 15 of 30
      for group 3, and 2 of 30 for group 4. The results suggest that, in vitro,
      Thermafil GT may be more prone to extruding gutta-percha past the apical foramen
      than Thermafil Plus.

PMID- 15167471
TI  - Perforation repair comparing two types of mineral trioxide aggregate.
AB  - The purpose of this study was to evaluate the ability of two types of mineral
      trioxide aggregate (MTA) to seal furcal perforations in extracted human molars
      using an anaerobic bacterial leakage model. Forty, human, maxillary and
      mandibular molars were randomly divided into two experimental groups of 18, with
      two teeth used as positive controls and two teeth without perforations used as
      negative controls. Experimental group 1 was repaired with gray-colored MTA and
      group 2 with off-white-colored MTA. A dual-chamber, anaerobic, bacterial-leakage
      model was assembled. Brain-heart infusion broth with yeast extract, hemin, and
      menadione was used as the culture broth for Fusobacterium nucleatum. Two of 18
      gray-colored MTA samples leaked and three off-white-colored MTA samples leaked.
      There was no significant difference between the two types of MTA in preventing
      leakage of F. nucleatum past furcal perforation repairs.

PMID- 15167472
TI  - Evaluation of apical debris removal using various sizes and tapers of ProFile GT
      files.
AB  - The purpose of this study was to evaluate the effect of preparation taper using
      size #20 or size #40 ProFile GT files on the ability to introduce irrigant and
      remove debris from root canals. Forty-eight bilaterally matched pairs of
      extracted teeth were instrumented using.04-,.06-,.08-, and.10-tapered files with
      one tooth of each pair enlarged to size #20 and the other to size #40. The teeth
      were sectioned at 1 mm and 3 mm from the apex, and the amount of remaining debris
      was calculated as a percentage of the total lumen area. The following variables
      were evaluated: apical preparation size, preparation taper, total volume of
      irrigation, depth of irrigation needle penetration, and number of instrument
      changes needed to reach working length. Compared with the size #40 preparations,
      a significantly greater percentage of remaining debris was observed in the size
      #20 preparations at the 1-mm level for all tapers except the.10 taper group in
      which there was no significant difference (p = 0.982). There were no significant
      differences between any groups at 3 mm. Results suggest that debris is more
      effectively removed using.04,.06, and.08 ProFile GT instruments when the apical
      preparation size is larger (size #40) compared with size #20 apical preparations.
      When a taper of.10 can be produced at the apical extent of the canal, there is no
      difference in debris removal between the two preparations sizes.

PMID- 15167474
TI  - Comparison of hand stainless steel and nickel titanium rotary instrumentation: a
      clinical study.
AB  - The aim of this study was to compare the effect of hand instruments and rotary
      nickel titanium Flex-Master files used by eight experienced dentists in private
      practice on the extent of straightening of curved root canals. In patients, 110
      canals were prepared by FlexMaster instruments, and 84 canals were enlarged using
      hand instruments. After instrumentation, all canals were obturated. Preoperative
      and postoperative radiographs were taken of each tooth using customized bite
      blocks. Straightening of the canal curvatures was determined with a computer
      image analysis program. Preparation time and size of the master apical file were
      also recorded. The use of FlexMaster instruments resulted in significantly less
      straightening and a shorter preparation time (p < 0.0001) compared with hand
      instrumentation. Master apical file sizes were significantly greater for
      FlexMaster than for hand instruments (p < 0.01). This clinical study indicates
      that FlexMaster instruments prepared curved canals rapidly and with only minimal
      straightening.

PMID- 15167473
TI  - The effects of chlorhexidine gluconate (0.12%) on the antimicrobial properties of
      tooth-colored ProRoot mineral trioxide aggregate.
AB  - The purpose of this in vitro study was to determine whether the substitution of
      0.12% chlorhexidine gluconate for sterile water as a mixing agent would enhance
      the antimicrobial activity of tooth-colored ProRoot mineral trioxide aggregate
      (MTA) against Actinomyces odontolyticus (ATCC17982), Fusobacterium nucleatum
      (ATCC2586), Streptococcus sanguis (ATCC10556), Enterococcus faecalis (ER3/2S),
      Escherichia coli (SM10lambdapir), Staphylococcus aureus (ATCC6538), Pseudomonas
      aeruginosa (UME), and Candida albicans (ATCC10261). Two wells of 5-mm diameter
      were made in triplicate agar plates inoculated with standardized suspensions of
      each microorganism. MTA (33 mg) mixed with chlorhexidine (12 microl) or sterile
      water (12 microl) was placed to fill each well. Plates were incubated at 37
      degrees C as required for microbial growth. A blinded, independent observer
      measured zones of inhibition. All MTA samples inhibited microbial growth
      regardless of mixing agent. MTA/chlorhexidine showed significantly larger zones
      of inhibition (p < 0.0002, paired t test). In conclusion, substituting 0.12%
      chlorhexidine gluconate for water enhanced the antimicrobial activity of tooth
      colored ProRoot MTA.

PMID- 15167475
TI  - Evaluation of apical filling after warm vertical gutta-percha compaction using
      different procedures.
AB  - The aim of the present study was to evaluate the quality of endodontic sealing in
      the apical 4 mm of narrow and curved canals using different filling techniques.
      Human teeth were selected and assigned to four different techniques: group A,
      Schilder's warm vertical condensation; group B, Schilder's technique modified by
      using an electric heater; group C, Schilder's technique modified by compaction of
      the apical tract at body temperature; and group D, a modified vertical compaction
      with apical back-filling. A dye penetration test was performed, and specimens of
      group D showed increased apical sealing and reduced extension of voids. The use
      of the vertical compaction with apical back-filling technique allowed the
      creation of an effective apical plug and an excellent adaptation of back-filling
      to apical gutta-percha and to root canal walls.

PMID- 15167476
TI  - Root surface temperature rises in vitro during root canal obturation with
      thermoplasticized gutta-percha on a carrier or by injection.
AB  - The aim of this in vitro study was to measure the temperature rise on the outer
      root surfaces of teeth during four different root canal obturation techniques.
      Sixty extracted human maxillary and mandibular premolars with a single canal were
      used. After root canal cleaning and shaping, the teeth were randomly divided into
      four groups of 15 teeth each and obturated with Thermafil obturators or Soft-Core
      obturators using Ultrafil or Trifecta low-temperature thermoplasticized gutta
      percha techniques. Temperature changes on the external mesial root surfaces were
      measured using a thermal imaging camera. Lower temperature rises were found for
      Ultrafil and Trifecta techniques (2.14 degrees C and 2.03 degrees C,
      respectively) than for Thermafil and Soft-Core techniques (3.87 degrees C and
      3.67 degrees C, respectively). These findings suggest that solid core gutta
      percha combined with low-temperature injectable gutta-percha obturation
      techniques may impose less risk for thermal damage to the surrounding
      periradicular tissues.

PMID- 15167477
TI  - Resolution of furcation bone loss associated with vital pulp tissue after
      nonsurgical root canal treatment of three-rooted mandibular molars: a case report
      of identical twins.
AB  - This case report demonstrates the simultaneous development of furcation bone loss
      in three-rooted tooth #30 with vital pulp tissue in identical twins. In the first
      report, resolution of furcal bone loss was seen after nonsurgical root canal
      treatment. In the second report, furcal bone loss resolved after non-surgical
      root canal treatment, and periodontal therapy reduced probing depths to
      maintainable levels.

PMID- 15167478
TI  - Nonsurgical management of a dilacerated maxillary lateral incisor with type III
      dens invaginatus: a case report.
AB  - Type III dens invaginatus is a developmental anomaly characterized by an enamel
      lined channel that originates on the coronal surface and passes apically through
      part or all of the root and exits into the periodontal ligament. In this case
      report, a 13-yr-old male had a Type III dens that exited at the midroot level of
      tooth #7. At that same level, the root dilacerated severely to the mesial, and a
      periradicular radiolucency was present on the distal. A 12-mm periodontal defect
      was present on tooth #6 and a sinus tract was present. All maxillary anterior
      teeth responded normally to pulp vitality testing, and no other abnormal probing
      depths were present. The channel opening in the crown was located, and the
      channel was negotiated, enlarged, and filled with calcium hydroxide. Thirteen
      weeks later, the probing was normal and the canal was obturated with gutta-percha
      and restored. Two- and 6-yr recalls showed complete healing of the bony defects
      and continued normal responses to vitality testing.

PMID- 15167502
TI  - Measuring relative work values for home care nursing services in Japan.
AB  - BACKGROUND: Japan's system of Home Visit Nursing Care Stations (Station) began in
      1991. To maintain the quality of services in home health nursing provided by
      Stations, reimbursement needs to account not only for the number of home visits,
      but also for the time and intensity of nursing services. OBJECTIVES: This study
      aimed primarily to investigate the total work value and the three dimensions
      (time, mental effort, and physical effort) of actual visiting nursing services
      for the aged, and to quantify the contribution made by the three dimensions of
      nursing services to total work. The secondary purpose was to determine whether
      patient characteristics, nurse characteristics, and types of nursing services
      contributed to the variance in total work. Total work is defined as comprehensive
      work input of nursing services, with careful consideration given to both the
      intensity and duration of work. METHODS: Self-report questionnaires about actual
      visiting nursing services, based on the Resource-Based Relative Value Scale, were
      answered by 32 nurses from three Stations in urban Yokohama, Japan. RESULTS:
      Regression analysis showed that time and intensity (physical effort and mental
      effort) explained 96% the variance in total work. Time alone accounted for only
      39% of the variance in total work. Patient characteristics, nurse
      characteristics, and service type accounted for less variance in total work than
      did time and intensity. CONCLUSIONS: The study findings indicate that
      reimbursement of nursing services should reflect not only the time required for
      each visit, but also the intensity of nursing services provided, including mental
      effort and physical effort.

PMID- 15167503
TI  - Sleep is related to physical function and emotional well-being after cardiac
      surgery.
AB  - BACKGROUND: Emotional well-being and physical function are important quality-of
      life outcomes after cardiac surgery. Alterations in sleep patterns, including
      sleep deprivation and altered circadian patterning, also are common. The
      relations among sleep pattern alterations, physical function, and emotional well
      being are not well understood. OBJECTIVE: This study aimed to examine the
      relations of sleep patterns to physical function and emotional well-being 4 and 8
      weeks after cardiac surgery. METHODS: Cardiac surgery patients (n = 72) wore
      wrist actigraphs and completed sleep diaries for 3 days during postoperative
      weeks 4 and 8. They also completed the Epworth Sleepiness Scale, the Pittsburgh
      Sleep Quality Index, and the Medical Outcomes Survey Short Form 36 preoperatively
      and at postoperative weeks 4 and 8. Pearson correlations and hierarchical
      multiple regression analysis were used to analyze the data. RESULTS: Mean sleep
      efficiency was 71% at 4 weeks and 74% at 8 weeks, as measured with wrist
      actigraphy. According to participants' self-report, 64% experienced sleep
      disturbance at 4 weeks and 47% at 8 weeks. Sleep pattern variables, including
      sleep efficiency and self-reported sleep quality, explained 16% of the variance
      in physical function at 4 weeks. Self-reported sleep quality explained 8% of the
      variance in physical function at 8 weeks as well as 12% of the variance in
      emotional well-being at postoperative week 4 and 13% of the variance at
      postoperative week 8, after control was used for the contributions of baseline
      physical function, emotional well-being, age, and sex. CONCLUSIONS: The results
      suggest that sleep contributes to both physical functional and emotional well
      being 4 and 8 weeks after cardiac surgery.

PMID- 15167504
TI  - Psychometric evaluation of the Differentiation of Self Inventory for adolescents.
AB  - BACKGROUND: Evidence of psychometric support is needed for use of the
      Differentiation of Self Inventory with adolescents as a clinical assessment
      instrument to evaluate psychotherapeutic progress and outcomes, and for its use
      as a research instrument to evaluate the effectiveness of interventions on the
      basis of Bowen family systems theory. OBJECTIVE: To examine the reliability and
      validity of the 46-item, self-report Differentiation of Self Inventory (DSI) for
      use with adolescents. METHOD: An ex post facto research design was used to
      determine the psychometric properties of the DSI for adolescents, and to test
      theoretically grounded hypotheses drawn from Bowen theory that linked
      differentiation of self with chronic anxiety and symptom development. The DSI,
      the State-Trait Anxiety Inventory, and the Symptom Pattern Scale were
      administered to an ethnically diverse sample of 363 adolescents 14 to 19 years of
      age. RESULTS: The DSI full scale demonstrated good internal consistency
      reliability, with a Cronbach's alpha coefficient of.84. Factor analysis yielded a
      six-factor structure, representing the multidimensionality of the DSI items among
      adolescents. As hypothesized, differentiation of self mediated the relation
      between chronic anxiety and symptom development (p <.001), indicating that
      greater differentiation of self predicted fewer symptoms over and above chronic
      anxiety, and lending support to the construct validity of the DSI in adolescent
      populations. CONCLUSIONS: The results of this study support the use of the DSI
      with adolescents. Future longitudinal studies are needed for definitive causal
      conclusions regarding the role that differentiation of self plays as a mediator
      between the relation of chronic anxiety and symptom development.

PMID- 15167505
TI  - Predictors of sexual intercourse and condom use intentions among Spanish-dominant
      Latino youth: a test of the planned behavior theory.
AB  - BACKGROUND: Spanish-dominant Latino youth represent a growing yet underserved
      segment of the U.S. population, especially in terms of protection from sexually
      transmitted HIV infection. There is evidence to suggest that this subgroup
      engages in both risk and protective behaviors that may be different from the
      behaviors of English-dominant Latino youth. OBJECTIVE: To examine theoretical
      predictors (attitude, subjective norm, behavioral beliefs, normative beliefs,
      control beliefs) of sexual intercourse and condom use with a sample of Spanish
      dominant Latino youth. METHODS: Participants in this study were part of a larger
      randomized controlled intervention designed to reduce the risk of sexually
      transmitted HIV among Latino youth. This article is based on preintervention data
      from 141 Spanish-speaking Latino adolescents (77 girls and 64 boys) who completed
      a Spanish version of the questionnaire. RESULTS: Multiple regression analyses
      showed significant effects of attitudes, perceived partner approval, self-pride,
      and parental pride on intentions to engage in sexual intercourse. Attitudes,
      intentions to engage in sex in the next 3 months, self-pride, parental pride,
      goals, and partner approval predicted sexual intercourse in the preceding 3
      months. Attitudes, subjective norms, self-efficacy, partner and parental
      approval, and impulse control beliefs were significant predictors of intentions
      to use condoms. CONCLUSIONS: This study represents initial efforts to address the
      needs of Spanish-dominant Latino youth. The identification of salient beliefs
      that may predict sexual risk and protective behavior are relevant to the design
      of culturally and linguistically effective interventions.

PMID- 15167506
TI  - Measuring leadership practices of nurses using the Leadership Practices
      Inventory.
AB  - BACKGROUND: Originally developed for educational use, the Leadership Practice
      Inventory (LPI) is used to measure leadership practices in nursing research.
      There is limited reporting of LPI psychometric properties when used to measure
      leadership practices of nurses. OBJECTIVE: This study aimed to investigate
      psychometric properties of the LPI when used to measure the leadership practices
      of nurses. METHOD: Data from 67 LPI-self and 347 LPI-observer respondents were
      used to establish LPI psychometric properties. Dimensionality of the LPI was
      investigated using exploratory principal components analysis, and LPI construct
      validity was established by exploring correlations with theoretically related
      concepts and a known-groups approach. The predictive validity of the LPI was
      investigated using regression analysis to determine whether observer-reported
      leadership practices of established and aspiring nurse leaders predict observer
      ratings of the effectiveness of the organization environment. Reliabilities of
      the new factor solution were explored. RESULTS: Factor analysis found that the
      identified three-factor solution has psychometric properties at least as strong
      as those found with the original five-factor LPI solution. DISCUSSION: The three
      factor solution is advocated for use in nursing research because of the strong
      psychometric properties, lighter respondent burden, and decrease in research
      costs, as compared with the traditional five-factor solution. When used as an
      educational tool, the five-factor LPI may be preferred because it may be more
      useful for examining a greater number of leadership behaviors.

PMID- 15167507
TI  - Predictors of infectious disease symptoms in inner city households.
AB  - BACKGROUND: Despite the fact that hygienic practices have been associated with
      reduced risk of infection for decades, the potential role of specific home
      hygiene and cleaning practices in reducing risk have not been explicated.
      OBJECTIVE: This study aimed to determine the incidence and predictors of
      infectious disease symptoms over a 48-week period in inner city households.
      METHODS: Cleaning and hygiene practices and the incidence of infectious disease
      symptoms were closely monitored prospectively for 48 months in 238 households.
      Each household was contacted by trained interviewers weekly via telephone, was
      visited monthly, and underwent an extensive home interview quarterly. RESULTS:
      The incidence of new symptoms in the month before quarterly home visits ranged
      from 8.9% to 12.4% for individuals and from 32% to 39.7% for households. Four
      factors were significantly associated with infection. Drinking only bottled water
      increased risk (relative risk [RR], 2.1; 95% confidence interval [CI], 1.2-3.7).
      Using hot water (RR, 0.7; 95% CI,.5-.9) and bleach (RR, 0.29; 95% CI,.23-.66) for
      laundry and reporting that germs were most likely to be picked up in the kitchen
      (RR, 0.5; 95% CI,.3-.8) were protective. No other hygiene practices, including
      hand washing, were associated with infection risk. CONCLUSIONS: Further studies
      of a potential role for bottled water in infections are warranted, as is a
      renewed appreciation for the potential protective role of laundry practices such
      as using bleach and hot water.

PMID- 15167508
TI  - Older men's health: motivation, self-ratings, and behaviors.
AB  - BACKGROUND: There is a documented need to examine the complex motivational
      systems that lead individuals to adopt health-promoting behaviors and to evaluate
      the psychosocial aspects of male health. A study focused on health motivation as
      a determinant of self-rated health and health behaviors among older men was
      therefore undertaken. OBJECTIVES: This study aimed to explore the relations among
      health motivation, self-rated health, and health behaviors in community-dwelling
      older men. METHODS: A descriptive, correlational survey design was used for this
      study of 135 community-dwelling men ages 55 years and older. The questionnaire
      packet included a demographic tool, the Older Men's Health Program and Screening
      Inventory, the Health-Promotion Activities of Older Adults Measure, and the
      Health Self-Determinism Index. RESULTS: Older men with more intrinsic motivation
      rated their health as better (p <or=.001) and assessed their lifestyles as more
      healthy (p <or=.001) than did their counterparts with more extrinsic motivation.
      Whereas anticipated benefits (a potential motivator) were significantly related
      to health-promoting behaviors (p <or=.001), health program attendance (p
      <or=.001), and health screening participation (p <or=.01), the Health Self
      Determinism Index score did not demonstrate significant relations with any of
      these three variables. CONCLUSIONS: The findings suggest that promoting self
      motivation may be key to increasing older men's perceptions of health and well
      being. Further exploration of anticipated benefits as a motivator of health
      promotion activities is warranted, as well as intervention studies to promote
      older men's health screening and program attendance.

PMID- 15167509
TI  - Lifelines: a life history methodology.
AB  - BACKGROUND: Life histories are data collection strategies that detail an
      individual's life Lifelines are a visual depiction of a life history, displaying
      events in chronological order and noting the importance, or meaning, of events.
      APPROACH: A sample lifeline from a study of young women's developmental
      transitions used to demonstrate the application of this technique to nursing
      research. A review life histories as well as lifeline techniques, analysis, and
      applications is included. DISCUSSION: Life history has been used extensively as a
      data collection method research, theory development, and clinical practice. The
      lifeline facilitates recollection and sequencing of personal events. The lifeline
      activity can be triangulated with other data collection methods such as
      interviews and focus groups to confirm and complete a life history or to place a
      particular research construct or clinical problem in the con text of other
      events.

PMID- 15167510
TI  - Research in nuclear medicine.

PMID- 15167511
TI  - Composite SISCOM images in mesial temporal lobe epilepsy: technique and
      illustration of regions of hyperperfusion.
AB  - OBJECTIVE: To outline and validate a technique for subtraction ictal single
      photon emission tomography (SPET) co-registered to magnetic resonance imaging
      (MRI) (SISCOM), which allows non-linear co-registration of groups of subtraction
      SPET images to a single, template image. METHODS: In patients with mesial
      temporal lobe epilepsy, we used linear and non-linear transformation steps to co
      register ictal and interictal images to a template SPET, then used the resultant
      ictal and interictal images to produce subtraction images. Statistical changes in
      subtraction SPET before and after the transformation steps in individual subjects
      were documented to validate the technique. Subtraction SPET images were
      thresholded to include pixel values 1 standard deviation (SD) above zero, and
      converted to binary. Images were combined by simple addition of images to form
      the final composite image. Final results were co-registered to a template MRI to
      demonstrate the regions most commonly hyperperfused in mesial temporal lobe
      epilepsy. RESULTS: Linear and non-linear transformation steps induced only small
      changes in standard deviations of subtraction SPET, typically approximately 1
      pixel value. The final composite SISCOM images showed the anterior temporal lobe,
      insula and basal ganglia as the most commonly hyperperfused regions during mesial
      temporal lobe epileptic seizures. CONCLUSION: Our technique resulted in only
      small changes in statistical characteristics of individual subtraction SPET
      studies, and was acceptable for the purpose of creating composite SISCOM images.

PMID- 15167512
TI  - Natural history, diagnosis, treatment and outcome of papillary thyroid
      microcarcinoma (PTMC): a mono-institutional 12-year experience.
AB  - The clinical and histopathological records of 149 consecutive patients with
      papillary thyroid microcarcinoma (PTMC), homogeneously studied and operated on by
      the same surgeon in the period 1990 to 2001, were reviewed. After a mean 6.5-year
      follow-up, three cases of loco-regional recurrence (2%) were observed. These
      three patients had all undergone partial thyroidectomy only and tumour relapse
      occurred in the residual thyroid tissue. No recurrence was observed in patients
      treated by total thyroidectomy and I. At variance with other reported series, no
      lymph node recurrence was observed in our series, in particular in the group of
      23 patients with evidence of nodal metastases at initial diagnosis (three of whom
      were revealed by I scan after surgery). Therefore, a preventive effect of I
      treatment in our patient population can be hypothesized. However, prolonged
      follow-up will be necessary to clarify this. Due to the inability of current
      imaging modalities to select pre-operatively PTMC patients at risk for recurrence
      (presence of thyroid capsular invasion, multifocality and microscopic lymph node
      metastases), it appears reasonable to offer the patient total thyroidectomy when
      a pre-operative diagnosis of PTMC is reached. Moreover, the policy of our thyroid
      cancer centre is that, in these patients, post-surgical I scan should be obtained
      in order to detect unknown metastatic deposits, and I treatment should also be
      considered in patients with poor clinical and histopathological prognostic
      factors. In contrast, in patients operated on for benign thyroid disease and with
      delayed diagnosis of PTMC at definitive histopathological examination, re
      operation might be avoided in the presence of unifocal disease without thyroid
      capsular invasion and with ultrasound-'normal' residual thyroid tissue. Close
      clinical and ultrasound follow-up is recommended, especially in patients who have
      undergone conservative surgery only.

PMID- 15167513
TI  - Do electrocardiographic changes with adenosine myocardial perfusion imaging
      predict ischaemia in patients with left ventricular hypertrophy?
AB  - BACKGROUND: Electrocardiographic (ECG) changes during adenosine myocardial
      perfusion imaging (MPI) correlate with severe coronary artery disease and the
      presence of collaterals. However, the significance of these changes during
      adenosine MPI in patients with left ventricular hypertrophy (LVH) on baseline
      electrocardiogram is less well understood. OBJECTIVE: To evaluate whether ECG
      changes on adenosine MPI predict ischaemia in patients with LVH. METHODS: We
      reviewed retrospectively 454 consecutive patients who had undergone adenosine MPI
      at our institution. The baseline electrocardiogram was reviewed to determine
      whether or not LVH was present. All patients were administered adenosine at 140
      microg x kg x min for a total of 6 min and Tc-sestamibi was injected at 3 min
      into the protocol. None of the patients underwent any form of exercise during the
      stress test. RESULTS: Of the 146 patients with LVH, 10 had stress ECG changes
      suggestive of ischaemia and 40 had evidence of ischaemia on MPI. Similarly, of
      the 308 patients without LVH, 43 had stress ECG changes suggestive of ischaemia
      and 68 had ischaemia on MPI. The sensitivity and specificity of stress ECG
      changes in predicting ischaemia on perfusion in patients with LVH were 12.5% and
      95.3%, respectively, with a positive predictive value of 50% and a negative
      predictive value of 74.3%. CONCLUSION: ECG changes suggestive of ischaemia in
      patients with LVH are very specific for ischaemia on MPI, and their significance
      is similar to that in patients without LVH.

PMID- 15167514
TI  - Oestrogen increases myocardial blood flow in men: assessment by 13N-ammonia
      positron emission tomography.
AB  - OBJECTIVES: Oestrogen has been shown to increase nitric oxide-mediated
      vasodilatation and modulate sympathetic tone in postmenopausal women. We
      investigated the acute effects of oestrogen on the coronary microcirculation in
      men. METHODS: Myocardial blood flow was quantified using N-ammonia positron
      emission tomography before and 20 min after an intravenous administration of
      conjugated oestrogen (10 mg) in nine healthy men. RESULTS: There were no
      significant changes in either systemic blood pressure or heart rate before and
      after oestrogen infusion. However, myocardial blood flow was increased by
      oestrogen from 0.88 +/-0.06 to 1.05+/-0.09 ml x g x min (P<0.05). Although serum
      levels of nitrite/nitrate (end products of nitric oxide) were not increased,
      circulating norepinephrine (noradrenaline) levels were decreased after the
      administration of oestrogen from 401+/-114 to 346+/-112 pg x ml (P<0.01). A
      significant negative correlation was found between myocardial blood flow and
      plasma norepinephrine levels (r=-0.67, P<0.05). CONCLUSIONS: A single
      administration of oestrogen enhanced myocardial circulation in healthy men. The
      oestrogen-induced increase in myocardial blood flow may be due to direct effects
      on the coronary circulation or through the modulation of norepinephrine levels,
      rather than the production of nitric oxide.

PMID- 15167515
TI  - Quantitative lung perfusion scan as a predictor of aerosol distribution
      heterogeneity and disease severity in children with cystic fibrosis.
AB  - BACKGROUND: The assessment of lung ventilation by radionuclide imaging has proved
      useful for the optimization of aerosol therapy in children with cystic fibrosis.
      Further analysis of lung perfusion may provide additional information. METHODS:
      Quantitative analysis of regional lung aerosol distribution (Tc phytates) and
      perfusion (Tc macroaggregates) homogeneity was performed in 18 children with
      cystic fibrosis, using the third and fourth spatial moments (skew and Kurtosis)
      of count distribution. Patients were chosen from a prospective study whose goal
      was to compare the efficacy of two nebulization methods of a radiolabelled
      aerosol: one session involved a nebulizer activated by patient inspiratory flow
      (control session), whereas the other involved a nebulizer powered by a pressure
      support device (PS session). RESULTS: Quantitative regional distribution of
      perfusion was similar to aerosol distribution, although skew and Kurtosis were
      lower, indicating better homogeneity. Perfusion skew was inversely correlated
      with pulmonary volumes and Shwachman score, even more significantly than
      ventilation skew. Using receiver operating characteristic curve analysis, a
      perfusion skew threshold of 0.67 was predictive of disease severity (FEV1 > or
      =60% or FEV1 <60%) with 86% sensitivity and 91% specificity. Furthermore, same
      skew threshold allowed the identification of patients who were 'PS responders'
      (greater amount of radioactivity deposited after the PS session) or 'PS non
      responders' with 80% sensitivity and 77% specificity. CONCLUSION: Quantification
      of regional lung perfusion is easy to perform and heterogeneity of the
      distribution is closely correlated to disease severity. Moreover, perfusion skew
      can identify patients who are likely to benefit from pressure support (to
      optimize aerosol therapy) and may be helpful for orienting potential non
      responders towards alternative therapies.

PMID- 15167516
TI  - First-pass scintigraphy with (99m)Tc macroaggregated albumin: a method for
      evaluating pulmonary arterial flow pulsatility.
AB  - OBJECTIVES: The aim of this work was to develop and describe a non-invasive
      scintigraphic technique to detect flow pulsatility in peripheral pulmonary
      arteries. METHODS: Ten normal volunteers were submitted to a first-pass
      scintigraphy using Tc macroaggregated albumin (Tc-MAA). A time-activity curve was
      generated for the right lung lateral third. Activity was shown to be restricted
      to the arterial compartment of the lungs, since there was no detectable
      progression of the radiopharmaceutical to the systemic circulation. Consequently,
      the rise in lung activity was attributed to the arterial inflow and the first
      derivative of the time-activity curve was assumed to represent pulmonary arterial
      flow. RESULTS: Pulmonary flow curves showed two main positive peaks in six
      volunteers, followed by a third small peak in three others. Flow was predominant
      during systole, with an important reduction in magnitude before the diastolic
      peak, leading to a negative count variation in eight subjects. This pattern is
      comparable to that described in central pulmonary vessels by different methods.
      CONCLUSIONS: First-pass scintigraphy with Tc-MAA was able to detect flow
      pulsatility in pulmonary arteries. These results need to be confirmed in a larger
      number of individuals, and, if shown to be reproducible, may increase our
      understanding of lung flow physiology, and of its modifications in the presence
      of cardiopulmonary diseases.

PMID- 15167517
TI  - Relationships between oxygen and glucose metabolism in human liver tumours:
      positron emission tomography using (15)O and (18)F-deoxyglucose.
AB  - BACKGROUND: Recently, investigators have measured glucose utilization in liver
      tumours using F-deoxyglucose positron emission tomography (FDG PET) in order to
      characterize tumours and predict therapeutic effects. However, the detectability
      of liver tumours by this method remains unclear. In addition, no study has
      examined the association between oxygen and glucose metabolism in liver tumours
      using PET. AIM: To evaluate these associations in human liver tumours in vivo
      using O and FDG. METHODS: Thirteen patients with liver tumours were studied: six
      with hepatocellular carcinoma (HCC), one with cholangiocarcinoma (CCC) and six
      with metastatic colon cancer (MET). We measured regional tumour blood flow (Ft),
      regional oxygen extraction fraction (OEF) and regional metabolic rate of oxygen
      (MRO2) using O PET. Using FDG PET, we determined a standardized uptake value
      (SUV) for liver tumours as an index of glucose metabolism. RESULTS: The mean
      values (mean+/-SE) for Ft, OEF, MRO2 and SUV were 42.5+/-7.0 ml x (100 g) x min,
      43.4+/-4.9%, 2.57+/-0.39 ml x (100g) x min and 4.01+/-0.36, respectively. SUV for
      MET (4.44+/-0.48) was higher than that for HCC (3.52+/-0.59), and the blood flow
      in MET [31.4+/-4.1 ml x (100 g) x min] was lower than that in HCC [57.1+/-12.4 ml
      x (100 g) x min]. Significant negative correlations were noted between MRO2 and
      SUV (r=-0.741, P=0.004), and between Ft and SUV (r=-0.713, P=0.006). No
      correlation was apparent between Ft and OEF (r=-0.348, P=0.24), or between OEF
      and SUV (r=-0.023, P=0.94). CONCLUSION: O and FDG PET showed a significant
      negative correlation between MRO2 and SUV in human liver tumours. In addition,
      MRO2 depends on Ft rather than on OEF.

PMID- 15167518
TI  - Limitations of (99m)Tc tetrofosmin in assessing reversal effects of verapamil on
      the function of multi-drug resistance associated protein 1.
AB  - BACKGROUND: Previous reports have demonstrated the feasibility of scintigraphic
      assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding
      cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin
      (TF). Furthermore, the potential of these tracers for evaluating the effects of
      reversal agents for MDR has been documented. However, most reversal agents
      simultaneously affect cationic ion transporters related to tracer accumulation in
      tumours. METHODS: The uptake of Tc-TF was examined in the MCF7/WT cell line, a
      wild-type breast cancer cell line that does not exhibit MDR, and its subclonal
      etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one
      of the multi-drug resistance associated proteins (MRPs), in the presence of
      increasing concentrations of verapamil, a classical MDR modulator. In the absence
      of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did
      MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of
      verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand,
      verapamil also increased tracer uptake in MCF7/WT cells, which was readily
      appreciated when the uptake values were corrected by viable cell numbers: an
      approximately 100% increase of Tc-TF uptake was observed in comparison with that
      in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase
      occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention
      of radioactivity in both MCF7/WT cells and MCF7/VP cells. CONCLUSION: These
      results suggest that cellular functions other than MRP1 function, probably
      cationic ion transporters, are simultaneously and significantly involved in the
      verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may
      overestimate the reversal effects of modulators on chemoresistance caused by MRP1
      when the modulators simultaneously affect ion transporters.

PMID- 15167519
TI  - Synthesis and evaluation of 5,7-dihydro-3-[2-[1-(4-[18F]-fluorobenzyl)-4
      piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one for in vivo mapping
      of acetylcholinesterase.
AB  - OBJECTIVES: Acetylcholinesterase (AChE) is an important cholinergic marker for
      the diagnosis of Alzheimer's disease (AD). A recent study has demonstrated that C
      labelled 5,7-dihydro-7-methyl-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H
      pyrrolo[3,2-f]-1,2-benzisoxazol-6-one (CP-126,998) shows promising results. The
      demethylated form of this ligand (CP-118,954) is a more potent and selective
      inhibitor than CP-126,998. In this study, therefore, CP-118,954 was labelled with
      F and evaluated for the in vivo mapping of AChE. METHODS: The 4-fluoro (1). and 2
      fluoro (2). derivatives of CP-118,954 were synthesized from 4-methyl-3
      nitroanisole in 11 steps. Their in vitro binding affinities to AChE were measured
      using Ellman's method. The preparation of [F]-1 was carried out by reductive
      alkylation of the piperidine precursor with 4-[F]-fluorobenzaldehyde, followed by
      high-performance liquid chromatography (HPLC) purification. In vitro
      autoradiography was performed by incubating rat brain coronal slices with [F]-1.
      Tissue distribution studies were performed in mouse brain and the data were
      expressed as the percentage of the injected dose per gram of tissue (%ID x g).
      RESULTS: Two fluorine-substituted AChE inhibitors were synthesized and their in
      vitro binding data showed that the 4-fluoro and 2-fluoro derivatives (1 and 2)
      had similar or superior binding affinity to that of the unsubstituted ligand, CP
      118,954. The F-labelled ligand was synthesized in 20-35% radiochemical yield
      (EOS) and with high effective specific activity (36-42 GBq x micromol).
      Autoradiography showed high uptake of [F]-1 in the striatum and this striatal
      uptake was completely inhibited by the unlabelled ligand 1. Tissue distribution
      studies demonstrated that high radioactivity was accumulated in the striatum, an
      AChE-rich region. CONCLUSIONS: This study demonstrates that [F]-1 may hold
      promise as a radioligand for the in vivo mapping of AChE.

PMID- 15167520
TI  - (99m)Tc-dextran scintigraphy to detect disease activity in patients with
      rheumatoid arthritis.
AB  - AIM: To test the applicability of Tc-dextran joint scintigraphy in the assessment
      of disease activity in patients with rheumatoid arthritis (RA), and to compare it
      with the clinical disease activity scores and laboratory parameters. METHODS:
      Twenty-seven patients with RA were investigated using Tc-dextran joint
      scintigraphy. The images were evaluated semi-quantitatively and the regional
      uptakes of the radiopharmaceutical were calculated for the knee, wrist and ankle
      joints. The clinical and laboratory parameters were collected and fully analysed.
      An articular Ritchie index (a tender joint score), the number of swollen joints
      (Sw), the number of tender joints, the morning stiffness (h), the total Ritchie
      articular index (R), the visual analogue scale (VAS) and the Disease Activity
      Score (DAS) were determined for all patients. RESULTS: Compared with controls,
      patients with RA had significantly higher regional Tc-dextran uptake in the knee,
      wrist and ankle joints (P=0.001). The regional Tc-dextran uptake showed no
      correlation with the patient's age, gender, duration of disease, number of
      swollen joints (Sw), number of tender joints, morning stiffness (h), VAS, total
      Ritchie articular index and DAS, or any laboratory parameters. There was a
      significant correlation between the regional Tc-dextran uptake for individual
      joints and the articular Ritchie index of the right and left wrist (r=0.42,
      P=0.03; r=0.45, P=0.02), right and left knee (r=0.66, P<0.0001; r=0.80, P<0.0001)
      and right and left ankle (r=0.47, P=0.014; r=0.76, P<0.0001), respectively.
      CONCLUSIONS: This study demonstrates that Tc-dextran scintigraphy is a sensitive
      method to detect active joint inflammation and could be useful in the management
      of patients with RA.

PMID- 15167521
TI  - Characterization of the ideal candidate for knee radiosynoviorthesis treatment in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: (1). To identify the main parameters that positively influence the
      outcome of knee radiosynoviorthesis (RSO) in patients with rheumatoid arthritis
      (RA) and (2). to determine the ideal candidate for this procedure. METHODS: We
      considered 80 knees (in 57 patients) that had undergone follow-up for at least 5
      years and/or prosthesis implantation after RSO treatment. The parameters
      evaluated included age, gender, oligo-articular or polyarticular involvement,
      disease progression, radiological joint damage (Larsen scale), instability and/or
      axial deviation, body mass index (BMI), and psychological motivation for
      prosthesis implantation. RESULTS: Knee Larsen stage IV, presence of instability
      axial deviation, disease progression, psychological motivation to the surgical
      replacement and BMI higher than the 85th percentile were associated with a
      negative outcome for RSO (prosthesis implantation). CONCLUSIONS: The ideal
      candidate for the RSO treatment is a patient with a low Larsen stage, no
      instability and/or axial deviation and a BMI below the 85th percentile. A
      patient's psychological motivation for the treatment should be evaluated before
      the RSO procedure.

PMID- 15167522
TI  - High radioactive concentration of 99mTc from a zirconium [99Mo]molybdate gel
      generator using an acidic alumina column for purification and concentration.
AB  - BACKGROUND: Newer applications of radiopharmaceuticals in nuclear medicine
      require pertechnetate of moderate to high radioactive concentration. Hence there
      is a need to develop simple procedures for the concentration of pertechnetate,
      and such a procedure is given in this paper. METHODS: Ten to 20 ml of sodium
      [Tc]pertechnetate eluted in de-ionized water from a zirconium [Mo]molybdate
      (ZrMo) gel column generator was passed through 2 g of an acidic alumina bed (35 x
      8 mm) in order to remove the co-eluted traces of Mo and to retain the
      pertechnetate. The retained pertechnetate was then re-eluted, quantitatively, in
      3 ml of normal saline, from the alumina column. RESULTS: About a 4-fold increase
      in radioactive concentration of Tc was obtained (cf. approximately 10-12 ml
      normal saline is required for the elution of Tc from the gel column). Generators
      containing up to 22.2 GBq (600 mCi) Mo in 6-7 g ZrMo gel column (35 x 13 mm) were
      prepared and a radioactive concentration of Tc up to 4 GBq x ml (110 mCi x ml)
      was obtained on the first day of use. The overall recovery of Tc was >90%, Mo
      breakthrough was 10 to 10% and the duration of concentration was 3-5 min. The
      chemical impurity in terms of Al, Mo and Zr was <10 ppm each. The same procedure
      for the concentration of pertechnetate was applied to generators with 12-15 g
      ZrMo gel beds to obtain a higher capacity Tc gel generator, with similar
      findings.

PMID- 15167524
TI  - Truncation correction of fan beam transmission data for attenuation correction
      using parallel beam emission data on a 3-detector SPECT system.
AB  - BACKGROUND: When the simultaneous transmission computed tomography (TCT)/single
      photon emission CT (SPECT) acquisition protocol is applied to myocardial studies
      using a 3-detector SPECT, the narrow effective field of view of a fan beam
      collimator used for TCT acquisition may cause truncation artifacts on TCT images.
      In this paper, we propose a new method of correcting for the truncation of TCT.
      METHODS: The truncated parts of the TCT projection data are corrected using
      quadratic functions, based on the properties that the integral of non-truncated
      TCT projection data is constant at any projection angle and the position of the
      centre of gravity is focused on a fixed point. The usefulness of our method was
      investigated in phantom and human studies using a 3-detector SPECT equipped with
      one cardiac fan beam collimator for TCT and two parallel beam collimators for
      SPECT. We used Tl as a tracer for SPECT and Tc as an external source for TCT.
      RESULTS: The phantom and human studies showed that our method can adequately
      correct for the truncation of TCT data acquired using a fan beam collimator in a
      3-detector SPECT, as long as there is no truncation in SPECT data. CONCLUSION:
      Our method appears to be useful for improving the SPECT images obtained using
      simultaneous TCT/SPECT acquisition in a 3-detector SPECT. However, further
      studies will be necessary to establish the clinical usefulness of this method.

PMID- 15167523
TI  - Preparation of (166)Dy/(166)Ho-EDTMP: a potential in vivo generator system for
      bone marrow ablation.
AB  - BACKGROUND AND AIM: Bone-seeking radiopharmaceuticals have been proposed for
      delivering ablative radiation doses to marrow in multiple myeloma and other
      haematological malignancies. The aim of this research was to examine the
      feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with
      Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in
      vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter
      Ho is formed. METHODS: Dy was obtained by neutron irradiation of enriched Dy2O3
      in a TRIGA Mark III reactor. Labelling was carried out in an aqueous phosphate
      medium at pH 8.0 by addition of DyCl3 to EDTMP at a molar ratio 1:1.75. Dy/Ho
      labelled EDTMP was obtained with a 99.3+/-0.6% radiochemical purity determined by
      thin-layer chromatography and high-performance liquid chromatography. RESULTS: In
      vitro studies demonstrated that Dy/Ho-EDTMP is unstable after dilution in saline
      and stable in human serum and no translocation of the daughter nucleus occurring
      subsequent to beta decay of Dy which could produce release of Ho. Biodistribution
      in mice shows a fast blood clearance after administration of Dy/Ho-EDTMP with a
      skeletal uptake of 22.32+/-1.86% ID/g at 2 h and 20.12+/-1.94% ID/g after 10 d, a
      rapid renal elimination and no accumulation in other organs. Theoretical bone
      marrow absorbed dose calculations indicate that the Dy/Ho-EDTMP in vivo generator
      system would produce 7.80 times more radiation dose to marrow than that produced
      by Sm-EDTMP and 3.47 times more than Ho-DOTMP per unit of initial activity
      retained in the skeleton. CONCLUSION: The prepared radiolabelled EDTMP has
      adequate properties as a stable in vivo generator system for bone marrow
      ablation.

PMID- 15167528
TI  - What to expect from medical liability tort reform.

PMID- 15167529
TI  - Prenatal asphyxia requires immediate response.

PMID- 15167531
TI  - Assessing adults with mental disorders in primary care.
AB  - There is a high prevalence of mental and physical comorbidity. Increasingly,
      persons with mental disorders are seen in nonpsychiatric settings where
      recognition of comorbidity is more complex. This article notes the interactions
      between mental and physical disorders and provides an assessment approach to
      improve health outcomes for persons with mental illness who are seen in primary
      care.

PMID- 15167530
TI  - Treatment and prevention of dyslipidemia with rosuvastatin (Crestor).

PMID- 15167533
TI  - Chemical agents of terrorism: preparing nurse practitioners.
AB  - Nurse practitioners must exercise vigilant readiness to properly care for victims
      of chemical injuries. In this article, appropriate clinical management of each
      category of chemicals is addressed, including supportive and pharmacologic care.
      Triage decisions are explained and decontamination concerns are identified.
      Attention is directed at special populations such as children and the elderly.

PMID- 15167535
TI  - Helping patients choose the right blood glucose meter.
AB  - Self-monitoring of blood glucose is crucial to keeping diabetes controlled and
      decreasing the risk of complications (such as heart disease). Matching the
      patient to the right blood glucose meter is important. Thanks to recent
      technologic advances, the market seems to have something for everyone, from a
      voice-activated glucose meter for those who are vision-impaired to a software
      program that analyzes trends in glucose control by the week, the month, or time
      of day.

PMID- 15167536
TI  - Can NPs rely on self-blood pressure measurements?
AB  - The development of relatively inexpensive and automated devices has stimulated
      the use of self or home blood pressure (BP) monitors. This article provides a
      guide for NPs to understand when self-BP measurement (SBPM) is a reliable
      alternative to traditional in-office measurements.

PMID- 15167538
TI  - Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ
      of adult rat.
AB  - We examined the effects of EPO on expression of suppressor of cytokine signaling
      2 (SOCS2) and found that treatment of neural progenitor cells derived from the
      adult subventricular zone (SVZ) with recombinant human EPO (rhEPO) stimulated
      progenitor cell differentiation into neurons, but not astrocytes. Quantitative RT
      PCR revealed that SOCS2 mRNA levels were increased in the progenitor cells
      treated with rhEPO. Immunostaining showed that neurons but not astrocytes were
      SOCS2 immunoreactive. Incubation of the progenitor cells with rhEPO in the
      presence of a neutralizing antibody against EPO abolished the effects of EPO on
      neuronal differentiation and expression of SOCS2. Our data suggest that up
      regulation of SOCS2 in neuronal progenitor cells derived from the adult SVZ may
      regulate EPO enhanced neuronal differentiation.

PMID- 15167539
TI  - Units and rhythms of the brain are revealed.

PMID- 15167540
TI  - A long-range cortical network emerging with theta oscillation in a mental task.
AB  - Human scalp EEG has demonstrated that global coherence among distant areas
      increases during cognitive tasks, suggesting that oscillating neural activities
      work to generate global neuronal assemblies for cognitive functions. The theta
      oscillation in a frequency range of 4-8 Hz with large amplitudes which emerges
      during mental tasks around the frontal midline region is called fm theta. If
      theta oscillation concerns the global neuronal assemblies, fm theta should be
      associated with regional activities that depend on task conditions. In the
      present study, we examine the EEG-related brain activities by developing
      simultaneous EEG and fMRI during a mental calculation task. EEG-related negative
      BOLD was dominant over anterior medial regions, suggesting a major contribution
      of negative BOLD to fm theta. Negative and positive BOLD were found over distant
      regions. Functional connectivity analyses revealed that the connectivity varied
      remarkably according to mental conditions. In the rest condition, the
      connectivity was localized, whereas in the task condition, a long-range coherent
      network was formed by the anterior midline, posterior cingulate and right middle
      temporal cortices with linking between the right middle temporal and left lateral
      cortices during numerical processing. Further EEG analyses indicate that the long
      range coherent network executing cognitive functions is coordinated in the time
      window of theta oscillations.

PMID- 15167541
TI  - Neuronal expression of catechol O-methyltransferase mRNA in neonatal rat
      suprachiasmatic nucleus.
AB  - We examined the expression profile of catechol O-methyltransferase (COMT) mRNA
      and its protein in the neonatal rat hypothalamus by in situ hybridization and
      immunohistochemistry to clarify the sites of dopamine degradation. Strong COMT
      mRNA expression was observed in the suprachiasmatic nucleus (SCN) throughout its
      rostrocaudal extent at postnatal day 1 (P1) and P2, and the mRNA levels decreased
      gradually until P16. COMT mRNA was predominantly localized to the ventral and
      medial parts of the SCN. Intense COMT immunoreactivity was demonstrated in the
      ventral SCN and was detected in neuronal perikarya and processes at P1. Ependymal
      and microglial cells also exhibited strong COMT immunoreactivity. These results
      indicate that COMT may directly be involved in dopaminergic signaling in the
      neonatal SCN.

PMID- 15167542
TI  - Modulation of thermal pain-related brain activity with virtual reality: evidence
      from fMRI.
AB  - This study investigated the neural correlates of virtual reality analgesia.
      Virtual reality significantly reduced subjective pain ratings (i.e. analgesia).
      Using fMRI, pain-related brain activity was measured for each participant during
      conditions of no virtual reality and during virtual reality (order randomized).
      As predicted, virtual reality significantly reduced pain-related brain activity
      in all five regions of interest; the anterior cingulate cortex, primary and
      secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected).
      Results showed direct modulation of human brain pain responses by virtual reality
      distraction.

PMID- 15167544
TI  - Deficits in beat perception and dyslexia: evidence from French.
AB  - Recent research has suggested a novel link between deficits in the perception of
      cues relevant to speech rhythm (i.e., deficits in amplitude envelope rise time
      processing, or beat perception) and the phonological deficits seen in most
      dyslexic children. In this research, we investigated whether these beat
      perception deficits were specific to a stress-timed language, such as English, or
      whether they would generalize to languages with different rhythmic properties,
      such as French. Eighteen dyslexics, 18 reading level controls, and 20
      chronological age controls were tested on a battery of phonological tasks,
      reading tasks and psychoacoustic tests. The results suggest that deficits in the
      perception of cues important for speech rhythm may be universal in developmental
      dyslexia.

PMID- 15167543
TI  - Implantation of neural stem cells via cerebrospinal fluid into the injured root.
AB  - In avulsion injury of the dorsal root, regenerating axons cannot extend through
      the entry zone, i.e. the transition zone between peripheral and central nervous
      systems, due to the discontinuity between Schwann cells and astrocytes. We
      infused neural stem cells through the 4th ventricle in an attempt to enhance
      axonal growth in injured dorsal roots. Infused stem cells were attached to, and
      integrated into, the lesion of the root and became associated with axons in the
      same manner as Schwann cells or perineurial sheath cells in the peripheral nerve,
      and as astrocytes in the central nerve area. These findings suggest that neural
      stem cells integrated by infusion through CSF might have a beneficial effect on
      nerve regeneration by inducing a continuity of Schwann cells and astrocytes at
      the transition zone.

PMID- 15167545
TI  - Source analysis of the N170 to faces and objects.
AB  - To clarify the neural sources for the face-sensitive N170, ERPs were recorded in
      16 subjects viewing upright and inverted faces, and compared to seven object
      categories. Source analyses were performed for each category and each subject at
      the latency of the N170. Larger source intensities were found in the posterior
      superior temporal sulcus region (STS) for faces compared to objects. STS
      intensities were highly correlated to the N170 amplitude over both hemispheres
      only for faces. The results suggest that one of the major sources of the N170 is
      the STS region and that the larger N170 amplitude to inverted faces is due to
      increased activation of that source for inverted faces rather than a recruitment
      of additional areas.

PMID- 15167546
TI  - Responsiveness to repeated speech stimuli persists in left but not right auditory
      cortex.
AB  - Activation of the auditory cortex habituates with repeated stimulation. While
      behaviorally adaptive in most circumstances, decreasing auditory responsiveness
      could interfere with speech perception. We therefore tested whether auditory
      habituation differs for speech and non-speech stimuli and for left and right
      auditory cortex. We examined seven right-handed subjects in whom we had
      determined left-hemispheric language dominance by event-related blood flow
      assessment. We recorded magnetoencephalographic-evoked responses to trains of
      four sine tones or vowels and measured the decrement from the first to the last
      stimulus of the response component about 100 ms after stimulus onset (N1). For
      the sine tones there was a decrement in both hemispheres. Conversely, for vowels
      there was significant attenuation of the auditory decrement in the left compared
      with the right hemisphere (p=0.017). This left-hemisphere persistence in auditory
      responsiveness to vowels demonstrates that the human brain processes speech
      stimuli differently than non-speech stimuli and that the left-hemisphere plays a
      dominant role in this speech-specific auditory processing.

PMID- 15167547
TI  - Increased anxiety in mice lacking vitamin D receptor gene.
AB  - Vitamin D is a steroid hormone with many important functions in the brain,
      mediated through the vitamin D nuclear receptor. Numerous human and animal data
      link vitamin D dysfunctions to various behavioural disorders. To examine this
      problem, we studied whether genetic ablation of vitamin D receptors in mice may
      be associated with altered emotional behaviours. Here we show that the receptor
      deficient mice demonstrate increased anxiety-like behaviours when subjected to a
      battery of behavioural tests. These studies suggest that vitamin D and its
      receptors are an important factor in the brain, whose imbalance may significantly
      affect emotional behaviour.

PMID- 15167549
TI  - Long-term training affects cerebellar processing in skilled keyboard players.
AB  - We studied cerebellar hemodynamic responses in highly skilled keyboard players
      and control subjects during complex tasks requiring unimanual and bimanual finger
      movements. Both groups showed strong hemodynamic responses in the cerebellum
      during the task conditions. However, non-musicians showed generally stronger
      hemodynamic responses in the cerebellum than keyboard players. We conclude that,
      due to long-term motor practice a different cortical activation pattern can be
      visualized in keyboard players. For the same movements fewer neurons need to be
      recruited. The different volume of the activated cortical areas might therefore
      reflect the different effort necessary for motor performance in both groups.

PMID- 15167548
TI  - Smelling human sex hormone-like compounds affects face gender judgment of men.
AB  - Although strong cross-sensory interactions between visual, tactile and auditory
      modalities have already been shown, we know little about how chemosensory
      information affects processing in other sensory modalities. We studied whether
      smelling gender-specific odorous sex hormone-like steroids: 5-alpha-androgenst-16
      en-3-one (androgen) or oestra-1, 3, 5 (10), 16-tetraen-3-ol (estrogen) can bias
      face gender discrimination. We found that, as a result of inhalation of androgen,
      men perceive faces to be more masculine as compared to when they are exposed to
      estrogen. Our results provide evidence for specific cross-sensory effects of the
      gender-specific chemosensory cues on the categorization of visual face gender.

PMID- 15167550
TI  - Time predictability modulates pre-supplementary motor area neuronal activity.
AB  - Two monkeys were trained in a delayed sequential motor task in which the time
      interval between events and the delay duration were either fixed or variable.
      Single-unit neuronal activity was recorded in the pre-supplementary motor area
      (pre-SMA). During the delay, we observed a gradual increase in activity (build-up
      pattern) in the fixed but not in the variable condition. In the former but not in
      the latter, the monkey had the opportunity to estimate time duration.
      Consequently, the build-up pattern observed in the pre-SMA might represent the
      neuronal substrate of a time accumulator system proposed by previous authors on
      the basis of functional imaging data. Such a system could play a critical role in
      the working memory of temporal information.

PMID- 15167551
TI  - Long lasting effects of transcranial direct current stimulation on motor imagery.
AB  - Transcranial magnetic stimulation (TMS) was employed to probe the modulatory
      effects of transcranial direct current stimulation of motor cortex on motor
      evoked responses (MEPs) produced during motor imagery. MEP amplitudes at rest and
      during motor imagery were assessed before and for a period of 60 min after
      transcranial direct current stimulation (tDCS) applied over the primary motor
      cortex at 1 mA for 5 min. Cathodal stimulation induced a decrease of about 30% of
      MEP amplitude at rest and a 50% reduction of MEP size during imagery. Ten minutes
      after tDCS, MEPs at rest returned to baseline values while MEPs during motor
      imagery were suppressed for up to 30 min. No changes in MEP amplitude during
      imagery were found after anodal stimulation. tDCS could represent a powerful tool
      to modulate the excitability of motor areas involved in mental practice and motor
      imagery.

PMID- 15167552
TI  - Short-term plasticity of the primary somatosensory cortex during tool use.
AB  - Plastic changes within the primary somatosensory cortex (SI) related to tool use
      are reported. Subjects manipulated a small object with a pair of tongs or with
      their hand. Functional organization of SI during tool use was compared with that
      during executing the task with the fingers and during rest, respectively.
      Topography of SI was assessed using neuromagnetic source imaging based on tactile
      stimulation of the first (D1) and fifth digit (D5). We found that cortical
      representations of D1 and D5 are further apart during tool use than during non
      tool use and rest. Our data suggest that somatosensory cortical maps are part of
      the neural network representing the modified schema of the hand in which the tool
      was incorporated.

PMID- 15167553
TI  - Brain stem convergence of pelvic viscerosomatic inputs via spinal and vagal
      afferents.
AB  - Single medullary reticular formation (MRF) neurons receive ascending spinal
      inputs from multiple somatic and pelvic visceral territories. MRF neurons were
      examined for responses to both pelvic (PN) and vagus (abdominal branches: VAG
      abd) nerve stimulation, which dually innervate certain pelvic viscera. Recordings
      in 12 urethane-anesthetized male rats were performed. Of 121 PN-responsive MRF
      neurons, 50% responded to VAG-abd. Twenty-seven (22%) responded to colonic
      distention. All 121 neurons responded to noxious stimulation of somatic
      territories, including many areas outside the perigenital region (including the
      hindpaws, ears, face). These data demonstrate input originating from different
      spinal and cranial nerves. The functional significance of this viscerosomatic
      convergence to MRF is unknown, but could relate to sensory/autonomic integration
      for coordinating multiple bodily functions, including reproductive and
      eliminative events.

PMID- 15167554
TI  - Opposite visual field asymmetries for egocentric and allocentric spatial
      judgments.
AB  - The purpose of the present study was to investigate the relation between visual
      hemifields and spatial frames of reference, according to the idea that multiple
      representations of 3D space exist. Results from two experiments clearly show that
      an upper visual hemifield advantage only arises when allocentric spatial
      judgments are required in order to perform a location task, whereas a lower
      visual hemifield advantage arises when egocentric spatial judgments are required.
      Such a double dissociation was interpreted as due to the activity of two separate
      neural pathways operating specific transformations of visual input for different
      functional outputs: scene recognition, mostly relying on allocentric frames of
      reference and subserved by the ventral, occipito-temporal pathway of the visual
      system, and goal directed actions, mostly relying on egocentric systems and
      subserved by the dorsal, occipito-parietal pathway of the visual system.

PMID- 15167555
TI  - Oscillatory brain activity and transcranial direct current stimulation in humans.
AB  - The aim of this study was to induce changes of the oscillatory activity in the
      visual cortex of healthy human subjects by modulation of neuronal excitability
      using weak transcranial direct current stimulation (tDCS). tDCS is a non-invasive
      stimulation method which induces prolonged, polarity-dependent increases or
      reductions in cortical excitability. An increase in high frequency oscillatory
      activity in the beta and gamma frequency ranges is closely related in time to the
      N70 peak of the primary visual evoked potential (VEP), which is an early sensory
      component of visual activation. Therefore this potential can be used to observe
      tDCS-induced changes related to oscillatory activity. VEPs were recorded using
      sinusoidal luminance gratings in an on/off mode before, immediately after and 10,
      20, 30 min after the end of 10 min anodal or cathodal stimulation. Cathodal
      stimulation significantly decreased while anodal stimulation slightly increased
      the normalized beta and gamma frequency powers. We have shown here that tDCS
      transiently and reversibly changed the organized cortical activity elicited by
      visual stimulation. Since gamma activity is also related to a higher level of
      information processing, tDCS might be a suitable method to affect higher order
      cognitive processes.

PMID- 15167556
TI  - Post-hatch activity-dependent modulation of visual asymmetry formation in
      pigeons.
AB  - The embryonically induced visual lateralization in pigeons can be modified by
      occlusion of one eye after hatching. Here we show that this deprivation effect
      could be also attained by short-term blocking of retinal activity with
      tetrodotoxin (TTX), leading to a dominance of the ipsilateral hemisphere in a
      visual discrimination task. This lateralization pattern resulted from a
      performance increase conveyed by the non-deprived hemisphere, while performance
      with the TTX-injected eye did not differ from that of saline-injected controls.
      Thus, post-hatch modulation of visual lateralization is mediated by TTX
      sensitive, activity-dependent neuronal mechanisms. The transient silencing of one
      visual input alters the activity balance between the left and right eye system,
      enhancing visuoperceptive skills in the relatively higher active hemisphere.

PMID- 15167557
TI  - Changes in functional connectivity of human MT/V5 with visual motion input.
AB  - The neural basis of human mental function is characterized by interactions
      between brain regions. Temporal correlations in MR signals between areas may
      provide one method for investigating these interactions. This approach was used
      to examine functional connectivity in the motion processing system of the human
      brain. Correlations between MT/V5 and other brain regions were examined in a
      resting state (without visual stimulation) and in an active state produced by
      viewing moving concentric circles. A network of regions consistent with the known
      functional anatomy of visual processing was correlated with MT/V5 during rest.
      When subjects were viewing motion, a more limited network was correlated with
      MT/V5, suggesting MT/V5 was acting in concert with a smaller network specific to
      the task.

PMID- 15167558
TI  - Postnatal changes in TASK-1 and TREK-1 expression in rat brain stem and
      cerebellum.
AB  - Developmental changes in expression of two-pore domain K+ channels, TASK-1 and
      TREK-1, were investigated in the juvenile (postnatal day 13; P13) and adult
      (P105) rat brain stem and cerebellum using immunohistochemistry. In the juvenile,
      extensive TASK-1-like immunoreactivity (TASK-1-LIR) was seen among glial cells in
      the white matter (e.g., radial glia), which showed marked reduction in the adult.
      In contrast, TASK-1-LIR in neurons including cerebellar Purkinje and granule
      cells, hypoglossal and facial motoneurons, and ventrolateral medulla neurons was
      increased in the adult. TASK-1-LIR in neuroglia surrounding peripheral axons of
      cranial nerves was persistent. TREK-1-LIR was similar between ages, although TREK
      1-LIR was neuronal and present only in juvenile cerebellar external germinal
      layer. Present results suggest roles for TASK-1 and K+ homeostasis in neuro-glial
      interaction, neurogenesis, differentiation, migration, axon guidance,
      synaptogenesis and myelination.

PMID- 15167559
TI  - Autophagosome-like vacuole formation in Huntington's disease lymphoblasts.
AB  - In an effort to clarify cellular abnormalities in Huntington's disease without
      the confounding factor of gross degeneration and postmortem alterations
      associated with studies of the brain, we have examined HD patient lymphoblasts.
      We report pronounced vacuole formation in patients. The vacuoles possess
      huntingtin remnants and cathepsin B staining, a lysosomal marker, suggesting
      autophagy. The number and size of vacuoles parallel the number of polyglutamine
      repeats in patients. Treatment with staurosporine, which augments apoptosis,
      leads to increased vacuole formation in Huntington's disease cells but does not
      influence control cells. Our findings provide direct evidence for abnormalities
      in Huntington's disease tissues outside the brain under basal conditions.
      Autophagic cellular alterations may be utilized as peripheral markers of
      Huntington's disease pathology.

PMID- 15167560
TI  - Activity-dependent increase in beta-amyloid precursor protein mRNA expression in
      neurons.
AB  - Although beta-amyloid precursor protein (APP) has been suggested to play a role
      in neuronal survival and plasticity, the mRNA expression of APP has not been
      studied in terms of neuronal activity. In cultures of mouse cerebellar granule
      cells, we found that the levels of APP mRNA increased when a high concentration
      of potassium was present in the medium. A deprivation of membrane depolarization
      caused by lowering the K+ concentration decreased both mRNA expression and
      protein synthesis of APP. Increasing the concentration, however, restored mRNA
      expression, which was driven by the influx of Ca2+ through L-type voltage
      dependent calcium channels and mediated by de novo protein synthesis. Thus, APP
      mRNA expression is controlled in an activity-dependent manner in neurons.

PMID- 15167561
TI  - Inhibition by bis(7)-tacrine of 5-HT-activated current in rat TG neurons.
AB  - Whole-cell recordings were performed on rat trigeminal ganglion (TG) neurons as a
      modeling experiment to investigate the effect of bis (7)-tacrine, a potential
      anti-Alzheimer's disease (AD) drug, on 5-HT-induced current (I5-HT).
      Extracellular 5-HT activated a concentration-dependent inward current that was
      blocked by ICS 205930. Co-application of bis(7)-tacrine inhibited I5-HT markedly
      with IC50 at 2 x 10 M. Bis(7)-tacrine shifted the concentration-response curve
      for I5-HT rightwards with its maximum response unchanged and EC50 increased,
      suggesting that this inhibition was competitive in nature. Intracellular dialysis
      of GDP-beta-S did not block bis(7)-tacrine inhibition of I5-HT, which excluded
      the involvement of G-protein mediation. These results may offer possible modality
      to understanding the anti-AD mechanism of bis(7)-tacrine.

PMID- 15167562
TI  - Carbachol induces a form of long-term potentiation in lateral amygdala.
AB  - We examined the effects of carbachol, a muscarinic acetylcholine receptor
      agonist, on excitatory synaptic transmission at thalamo-amygdala synapses in rat
      brain slices. The application of a low concentration of carbachol (0.25 microM)
      produced a form of long-term potentiation (cLTP) and a transient suppression of
      synaptic responses, which was blocked by a muscarinic receptor antagonist,
      atropine (10 microM). M2 receptor agonist produced only a transient suppression,
      whereas M1 receptor agonist induced both a transient suppression and a long-term
      potentiation. Induction of cLTP required simultaneous low-frequency afferent
      stimulation, and was also dependent upon the activation of NMDA receptors.
      SQ22536 (50 microM), an adenylyl cyclase inhibitor completely blocked cLTP.
      Consistently, pretreatment with a maximal concentration of forskolin (10 microM)
      reduced cLTP.

PMID- 15167563
TI  - Children are sensitive to averted eyes at the earliest stage of gaze processing.
AB  - Event-related responses to a face with forward gaze or averted gaze (gaze task)
      and two equiluminous mosaic images (mosaic task) were recorded from healthy
      children aged 8-12 years and adults, using MEG and EEG. In children, a clear
      occipito-temporal magnetic field activity (P1m, around 140 ms) was observed
      bilaterally, and the right P1m amplitude was increased when viewing a face with
      averted gaze compared with that when viewing a face with forward gaze. This
      effect was not observed in adults. Furthermore, the source for the right P1m in
      children in the gaze task was mainly located around the putative human MT/V5
      area. These data suggest that the early occipito-temporal brain response observed
      as the P1m is a gaze-sensitive component in children.

PMID- 15167564
TI  - Bilateral slowing of mentally simulated actions after stroke.
AB  - The ability to mentally simulate motor actions was studied in 25 patients with
      stroke. The duration of imagined and executed movements of the arm and leg was
      compared. Both executed and imagined movements took longer with the affected
      limbs than with the unaffected limbs. For both tasks, the duration of movements
      with the unaffected limbs was longer in the imagined than in the executed
      conditions, indicating a lack of temporal congruence on that side. Because the
      temporal uncoupling was found in the limbs contralateral to the intact
      hemisphere, we propose that this reflects a general slowing in motor imagery that
      is an indirect consequence of the lesion, rather than a deficit in movement
      representation within the unaffected hemisphere per se.

PMID- 15167565
TI  - Distraction and reorientation in children: a behavioral and ERP study.
AB  - In the context of distraction, involuntary orienting to task-irrelevant
      deviations and the following reorienting to task-relevant stimulus information
      were studied in children aged 5-6 years. In an auditory distraction paradigm,
      reaction times were prolonged by 51 ms in trials including a task-irrelevant
      stimulus deviancy. Event-related potentials (ERPs) revealed a mismatch response
      (MMR) at 252 ms and a reorienting negativity (RON) 476 ms post-stimulus in
      response to deviating sounds. These behavioral and ERP effects resemble those
      reported for adults. We conclude that kindergarten children are prone to
      distraction, although they can quite effectively but not fully shield working
      memory operations from perturbating distracting information, and can recover from
      distraction in a similar way to adults.

PMID- 15167566
TI  - Neural correlates of song complexity in Bengalese finch high vocal center.
AB  - Auditory neurons in the songbird forebrain nucleus high vocal center HVC) show
      high selectivity to the temporal structure of bird's own song but the
      relationship between the degree of song complexity and neural selectivity is not
      known. We investigated the song temporal selectivity of HVC neurons by multi-unit
      recordings in seven male Bengalese finches with different song complexity.
      Results showed that HVC multi-units of the individuals with more complex songs
      responded strongly to each of the self-generated song elements but were
      relatively insensitive to the element order, while those with stereotyped songs
      responded only to the song elements ordered exactly as in the self-produced
      songs. Data suggest that the individually learned song syntax correlates with
      individualized temporal combination selectivity in HVC neurons.

PMID- 15167567
TI  - Action of MT-II on ghrelin-induced feeding in the paraventricular nucleus of the
      hypothalamus.
AB  - Ghrelin is a 28 amino-acid peptide that has been shown to induce positive energy
      balance when administered both peripherally and centrally. This effect appears to
      occur by increasing food intake and by reducing fat utilization. Ghrelin injected
      into the PVN increases food intake dose-dependently. The NPY receptor has been
      implicated in the orexigenic effect of ghrelin, but until now, the role of
      melanocortins on the effect of ghrelin in the PVN has not been reported. Sprague
      Dawley rats were stimulated to eat by PVN ghrelin. Pre-injection of 10 pmol of MT
      II into the PVN caused a significant decrease in ghrelin-induced feeding in both
      0-1 h and 0-4 h food intake studies. This finding indicates that MC 3/4-R
      signaling appears to be recruited by ghrelin, in the PVN, in its role to induce
      feeding.

PMID- 15167568
TI  - Neural synchronization deficits to auditory stimulation in bipolar disorder.
AB  - Patients with bipolar disorder show cognitive deficits and disorganized behavior,
      which may reflect a disturbance in neural synchronization. We tested whether EEG
      measures of auditory neural synchronization were abnormal in bipolar disorder.
      Nineteen symptomatic patients with bipolar disorder and 32 non-psychiatric
      control subjects were evaluated. Click trains (500 ms duration) presented at 20,
      30, 40 and 50 Hz were used to evoke EEG synchronization. Patients with bipolar
      disorder showed reduced power across the frequencies of stimulation. Phase
      locking across trials was also disturbed in bipolar disorder, consistent with
      poor phase synchronization between the stimulus and EEG. Abnormal high frequency
      neural synchronization may contribute to cognitive deficits in bipolar disorder.

PMID- 15167569
TI  - Cannabinoid agonist-induced sensitisation to morphine place preference in mice.
AB  - The influence of the endocannabinoid system on the sensitisation to the rewarding
      effects of morphine in the place conditioning paradigm was evaluated. In mice
      pretreated with morphine this drug induces place preference with lower doses.
      Pretreatment with non-rewarding doses of the cannabinoid agonist WIN 55,212-2
      (0.5 and 1 mg/kg) induces sensitisation to the rewarding effects of morphine.
      However, the pretreatment with the cannabinoid antagonist SR 144716A plus
      morphine or WIN 55,212-2 blocks it. Our results suggest the existence of cross
      talk between cannabinoids and opiates on the sensitisation to morphine and the
      implication of the endocannabinoid system in the process of sensitisation to
      opiates.

PMID- 15167570
TI  - Creating meaningful learning through autobiography and constructivist design.

PMID- 15167572
TI  - Does pathophysiology have to be boring?

PMID- 15167573
TI  - Unleashing creativity: seven strategies for successful learning.

PMID- 15167574
TI  - Cooperative learning: the ugly, the bad, and the good.

PMID- 15167575
TI  - Strategies for teaching public policy in nursing: a creative approach.
AB  - Professional discourse and facilitation of student-student and student-faculty
      interaction is at the heart of learning, especially with value-laden subjects
      such as politics and public policy. The authors discuss an online public policy
      course in nursing, specifically focusing on examples of successful strategies
      that inspired learning through communal expression.

PMID- 15167576
TI  - Critical care clinical experience for novice students: reinforcing basic nursing
      skills.
AB  - To better match students' learning priorities with their practicum experiences
      and to facilitate skills learning, undergraduate faculty devised the innovative
      strategy of incorporating a critical care rotation into the first semester of
      students' clinical experience. The authors describe the basics of this previously
      untested critical care clinical experience and the essential planning steps prior
      to implementation, including faculty approval, hospital administrative and nurse
      manager approval, preceptor identification and education, means of evaluating and
      grading the students, and evaluation of the overall experience.

PMID- 15167577
TI  - Can a journal club bridge the gap between research and practice?
AB  - It is imperative that nursing students learn to use research as a basis for
      making clinical decisions. The author discusses how a journal club was structured
      and designed to promote evidence-based practice and to reduce several of the
      barriers in utilizing research in the clinical setting. Vignettes illustrate the
      serendipitous events that also triggered the staff nurses' participation. An
      informal evaluation of the journal club is presented and suggestions for
      implementing future journal clubs are provided.

PMID- 15167578
TI  - Students' perceptions of online learning: implications for teaching.
AB  - Using the Internet to deliver nursing courses via distance education can
      facilitate learning on demand and promote learner-centered instruction. The
      authors describe 20 graduate nursing students' experiences with online learning.
      Students learn through reflection, exploration, use of critical thinking,
      interacting with others, sharing of information, and using resources. Key points
      of students' experiences with online learning were consistent with the
      Constructivism Theory. Implications for improving teaching are based upon the
      Constructivism Theory and include strategies for identifying learning goals and
      conditions for learning, as well as planning and implementing various methods of
      instruction.

PMID- 15167579
TI  - Applying the Revised Bloom's Taxonomy to a medical-surgical nursing lesson.
AB  - The Revised Bloom's Taxonomy provides a 2-dimensional framework for classifying
      cognitive learning. Classifying learning objectives by knowledge type in relation
      to cognitive process helps educators obtain a better understanding about intended
      learning, and enables them to design appropriate instruction and assessment
      methods. The authors demonstrate use of the Revised Bloom's Taxonomy to achieve
      congruence among intended learning, instructional activities, and assessment
      methods while teaching diagnostic reasoning for clients with myocardial
      infarction.

PMID- 15167580
TI  - Gender bias and discrimination in nursing education: can we change it?
AB  - Gender bias in nursing education impedes recruitment and retention of males into
      the profession. Nurse educators who are unaware of men's historical contributions
      to the profession may unknowingly perpetuate gender bias. The author describes
      how traditional stereotypes can be challenged and teaching/learning strategies
      can be customized to gender-driven learning styles.

PMID- 15167581
TI  - A community-campus partnership: influenza prevention campaign.
AB  - Service learning and community-campus partnerships foster the integration of
      educational goals and community need. The authors describe a school of nursing
      and a visiting nurse association partnership in which undergraduate and graduate
      students participated in an immunization campaign. Preparation, orientation, and
      evaluation of students based on special course objectives is presented.

PMID- 15167582
TI  - Evidence-based multicultural teaching methods.

PMID- 15167583
TI  - Polyomavirus nephropathy: what have we learned?

PMID- 15167584
TI  - Rapamycin protects allografts from rejection while simultaneously attacking
      tumors in immunosuppressed mice.
AB  - Cancer is an increasingly recognized problem associated with immunosuppression.
      Recent reports, however, suggest that the immunosuppressive agent rapamycin has
      anti-cancer properties that could address this problem. Thus far, rapamycin's
      effects on immunity and cancer have been studied separately. Here we tested the
      effects of rapamycin, versus cyclosporine A (CsA), on established tumors in mice
      simultaneously bearing a heart allograft. In one tumor-transplant model, BALB/c
      mice received subcutaneous syngenic CT26 colon adenocarcinoma cells 7 days before
      C3H ear-heart transplantation. Rapamycin or CsA treatment was initiated with
      transplantation. In a second model system, a B16 melanoma was established in
      C57BL/6 mice that received a primary vascularized C3H heart allograft. In vitro
      angiogenic effects of rapamycin and CsA were tested in an aortic ring assay.
      Results show that CT26 tumors grew for 2 weeks before tumor complications
      occurred. However, rapamycin protected allografts, inhibited tumor growth, and
      permitted animal survival. In contrast, CsA-treated mice succumbed to advancing
      tumors, albeit with a functioning allograft. Rapamycin's antitumor effect also
      functioned in severe combined immunodeficient BALB/c mice. Similar effects of the
      drugs occurred with B16 melanomas and primary vascularized C3H allografts in
      C57BL/6 mice. Furthermore, in this model, rapamycin inhibited the tumor growth
      enhancing effects of CsA. Moreover, in vitro experiments showed that CsA promotes
      angiogenesis by a transforming growth factor-beta-related mechanism, and that
      this effect is abrogated by rapamycin. This study demonstrates that rapamycin
      simultaneously protects allografts from rejection and attacks tumors in a complex
      transplant-tumor situation. Notably, CsA protects allografts from rejection, but
      cancer progression is promoted in transplant recipients.

PMID- 15167585
TI  - FTY: not just a homely drug.

PMID- 15167586
TI  - Preservation of porcine non-heart-beating donor livers by sequential cold storage
      and warm perfusion.
AB  - BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain
      viability of non-heart-beating donor (NHBD) livers that have undergone
      significant warm ischemic injury. However, the logistics of clinical organ
      retrieval are complex, and a period of cold storage before warm preservation
      would simplify the process. We have investigated the effects of short duration of
      cold preservation before normothermic preservation on the function of porcine
      NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm
      ischemia and then assigned to the following groups: group W (n=5), normothermic
      preservation for 24 hours; and group C (n=4), cold preservation in University of
      Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours
      (total preservation time 24 hours). Outcome parameters that were measured
      included bile production, serum transaminases and hyaluronic acid levels
      (cellular damage), and base deficit and glucose use (metabolic function).
      RESULTS: Group W livers had superior bile production, metabolic activity (base
      deficit and greater glucose use), and less evidence of hepatocellular damage
      (alanine aminotransferase, aspartate aminotransferase), and sinusoidal
      endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater
      necrosis and destruction of architecture on histology. CONCLUSION: Normothermic
      perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia
      and 4 hours of cold preservation. Even a short period of cold ischemia is
      significantly deleterious to the function of ischemically damaged (NHBD) livers.

PMID- 15167587
TI  - Effect of dopamine on inflammatory status in kidneys of brain-dead rats.
AB  - BACKGROUND: Brain death has been identified as an independent risk factor for
      chronic allograft dysfunction. In two independent retrospective clinical studies,
      we showed that dopamine treatment of brain-dead donors improves long-term kidney
      graft survival. The mechanisms underlying the protective effects of dopamine
      treatment in vivo have not been identified. To elucidate the mechanisms
      underlying the protective effect of dopamine on kidneys of brain-dead donors, we
      studied a model for brain death in rats. METHODS: In F344 rats, brain death was
      induced by epidural inflation of a 3F Fogarty catheter. Apneic animals were
      mechanically ventilated, and clinically relevant dosages of dopamine (2, 6, 10,
      or 14 microg/kg/min) were given for 6 hr from the onset of brain death.
      Ventilated, non-brain-dead animals served as controls. RESULTS: Dopamine
      significantly reduced renal monocyte infiltration and major histocompatibility
      class II and P-selectin expression in brain-dead animals. It also prevented
      further up-regulation of the inflammatory markers tumor necrosis factor-alpha and
      monocyte chemoattractant peptide-1. Concomitantly, the presence of inducible anti
      oxidant heme oxygenase-1, known for its cytoprotective effects, was strongly
      increased by dopamine. CONCLUSION: We identified several mechanisms underlying
      the protective effects of dopamine treatment on kidney grafts. The identification
      of these mechanisms may help to design more effective future strategies for
      treatment of cadaveric kidney donors.

PMID- 15167588
TI  - Prolonged survival of neonatal porcine islet xenografts in mice treated with a
      donor-specific transfusion and anti-CD154 antibody.
AB  - BACKGROUND: Combined treatment with a single donor-specific transfusion (DST) and
      a brief course of anti-mouse CD154 monoclonal antibody (mAb) to induce co
      stimulation blockade leads to long-term murine islet allograft survival. The
      authors hypothesized that this protocol could also induce long-term survival of
      neonatal porcine islet cell clusters (NPCC) in chemically diabetic
      immunocompetent mice and allow their differentiation into functional insulin
      producing cells. METHODS: Pancreata from 1- to 3-day-old pigs were collagenase
      digested and cultured for 8 days. NPCC were recovered and transplanted into the
      renal subcapsular space. Recipients included chemically diabetic nonobese
      diabetic (NOD)-scid and C57BL/6 mice that were otherwise untreated, treated with
      anti-CD154 mAb alone, or treated with DST plus anti-CD154 mAb. Plasma glucose
      concentration and body weight were measured, and xenografts were examined
      histologically. RESULTS: NPCC fully differentiated and restored normoglycemia in
      four of five diabetic NOD-scid recipients but were uniformly rejected by diabetic
      C57BL/6 recipients. Anti-CD154 mAb monotherapy restored normoglycemia in 4 of 10
      (40%) NPCC-engrafted, chemically diabetic C57BL/6 mice, but combined treatment
      with DST and anti-CD154 mAb restored normoglycemia in 12 of 13 (92%) recipients.
      Reversal of diabetes required 5 to 12 weeks. Surviving grafts were essentially
      free of inflammatory infiltrates 15 weeks after transplantation. CONCLUSIONS:
      Combination therapy with a single DST and a brief course of anti-mouse CD154 mAb
      without maintenance immunosuppression permits survival and differentiation of
      NPCC in diabetic C57BL/6 mice. Successful grafts were associated with durable
      restoration of normoglycemia and the absence of graft inflammation.

PMID- 15167589
TI  - Myoblast survival enhancement and transplantation success improvement by heat
      shock treatment in mdx mice.
AB  - BACKGROUND: Duchenne muscular dystrophy is a disease caused by the incapacity to
      synthesize dystrophin, which is implicated in the maintenance of the sarcolemma
      integrity. Myoblast transplantation is a potential treatment of this disease.
      However, most of the transplanted cells die very rapidly after their injection.
      Heat-shock proteins (HSPs) are over-expressed when cells undergo various types of
      stresses. Our goal was thus to investigate whether the expression of HSPs (HSP70
      in particular) could protect myoblasts from death after intramuscular injection.
      METHODS: HSP70 expression was induced by warming the cells at 42 degrees C for 60
      minutes. HSP70 over-expression was quantified by Western blot analysis. The in
      vitro effect of HSPs on cell survival was evaluated by fluorescence-activated
      cell sorter analysis using the Hoescht/propidium iodide-labeling technique, and
      their in vivo effects were investigated by transplanting TnI-LacZ myoblasts
      labeled with [methyl-14C] thymidine. RESULTS: Western blots indicated a sevenfold
      over-expression of the HSP70 after the heat-shock treatment. In vitro, the heat
      shock treatment protected 18% of the cells from staurosporine- (1 microM) induced
      apoptosis. HSPs also protected 10% of the cells from death induced by either
      tumor necrosis factor-alpha (30 ng/mL) or glucose oxydase (0.1 U/mL). In vivo,
      the treatment improved the cell survival by twofold 5 days after the graft and
      increased by fourfold the long-term graft success. CONCLUSIONS: The heat-shock
      treatment is a practical approach for improving the success of myoblast
      transplantation; in fact, using this kind of treatment, there is no need to
      genetically modify the cells before their transplantation.

PMID- 15167591
TI  - Preemptive living-donor kidney transplantation: clinical course and outcome.
AB  - BACKGROUND: Dialysis is not only associated with morbidity, it is also expensive.
      In developing countries, preemptive renal transplantation (Tx) may be a cost
      effective option, offering an additional benefit to conventional renal Tx.
      MATERIALS: Between March 1976 and March 2001, 1,279 first living-donor Txs were
      performed in our center. The 82 patients (6.4%) who underwent Tx without prior
      dialysis were compared with 1,197 patients who had been dialyzed before Tx.
      RESULTS: The dialysis-dependent group received more blood transfusions (65% vs.
      30%) before Tx. Actuarial graft and patient survival at 5 years was comparable in
      both groups (P =0.2 and P =0.8, respectively). The incidence of acute and chronic
      rejection was not different between the two groups. Mortality rate was also
      similar in the two groups. The main cause of death with a functioning graft was
      cardiovascular in the preemptive Tx group and chronic liver disease and infection
      in the control group. CONCLUSION: In the context of a developing country,
      preemptive Tx offers comparable patient and graft survival to conventional renal
      Tx and eliminates the complications, inconvenience, and cost of dialysis.

PMID- 15167590
TI  - Establishment of an immortalized human-liver endothelial cell line with SV40T and
      hTERT.
AB  - BACKGROUND AND AIMS: Liver endothelial cells (LECs) perform an essential role in
      important pathophysiologic functions in the liver. Establishment of a human LEC
      line facilitates advances in LEC research. Here, we present immortalization of
      human LECs using retroviral gene transfer of simian virus 40 large T antigen
      (SV40T) and human telomerase reverse transcriptase (hTERT). We also demonstrate
      excision of SV40T and hTERT with TAT-mediated Cre/loxP recombination and
      subsequent cell sorting. METHODS: First, human LECs were transduced with a
      retroviral vector somatostatin receptor (SSR)#69 expressing SV40T and hygromycin
      resistance genes flanked by a pair of loxA recombination targets. Then, cells
      were retrovirally superinfected with SSR#197 encoding hTERT and green fluorescent
      protein (GFP) cDNAs that were intervened by two loxBs. One SV40T-and hTERT
      immortalized LEC clone, TMNK-1, was established and analyzed for its biologic
      characteristics. RESULTS: The cells were hygromycin-resistant and uniformly
      positive for GFP expression. TMNK-1 expressed EC markers, including factor VIII,
      vascular endothelial growth factor receptors (flt-1, KDR/Flk-1), and CD34, showed
      uptake of Di-I-acetylated-low-density lipoprotein and angiogenic potential in
      Matrigel assays. After lipopolysaccharide treatment, TMNK-1 produced tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-6 and exhibited increased
      expression of intra-cellular adhesive molecule-1, vascular cellular adhesive
      molecule-1, and VE-cadherin. After treatment with TAT-Cre recombinase fusion
      protein, approximately 60% of TMNK-1 was negative for GFP expression, and
      subsequent cell sorting of this population for GFP allowed for collection of the
      reverted form of TMNK-1. CONCLUSIONS: This study demonstrates the utility and
      efficiency of the reversible immortalization procedure to expand primary human
      LECs for basic studies.

PMID- 15167592
TI  - A prospective, randomized study of coadministration of ketoconazole and
      cyclosporine a in kidney transplant recipients: ten-year follow-up.
AB  - BACKGROUND: In a prospective, randomized study, we previously proved the safety
      and financial benefits of the coadministration of ketoconazole (keto) and
      cyclosporine A (CsA) in patients. We report the 10-year follow-up of these
      patients and the controls. PATIENTS AND METHODS: In January 1992, 100 living
      related kidney transplant recipients were randomized into two groups: Group 1 (51
      patients) received 100 mg/day keto, and group 2 (49 patients) did not receive
      keto (control). Both groups were evaluated regarding graft function, CsA dose and
      levels, liver function tests, serum calcium and phosphorus, bone mineral density,
      and histopathologic assessment. RESULTS: Follow-up for 10 years showed that CsA
      dose reduction was maximum after 1 month (76.5%) and decreased gradually after 10
      years (64.6%). Acute rejection was diagnosed in 22% and 27% in the keto and
      control groups, respectively (P =0.27). In the control group, the acute rejection
      episodes were more frequent with poorer response to treatment. Chronic allograft
      nephropathy was statistically significantly less in the keto group.
      Hepatotoxicity and metabolic complications were similar in both groups. The
      annual cost saving of CsA was 60% after 1 year and 50% at the end of the study.
      CONCLUSIONS: We conclude that the long-term use of keto for CsA dose reduction in
      kidney transplant recipients is safe, tolerable, and cost-sparing and is
      associated with stable graft function.

PMID- 15167593
TI  - Tuberculosis in the transplant candidate: importance of early diagnosis and
      treatment.
AB  - BACKGROUND: Transplantation is contraindicated in candidates with active
      tuberculosis. The present study was undertaken to determine the clinical
      manifestations of tuberculosis in the transplant candidate and the prognosis of
      cases that inadvertently undergo transplantation. METHODS: This study was a
      retrospective study of tuberculosis cases diagnosed among 3,889 transplant
      candidates. All cases were diagnosed from respiratory or tissue samples obtained
      in the pretransplant period or during transplantation. RESULTS: We observed 7
      cases (0.18%) of active tuberculosis among 3,889 candidates. Two patients had a
      history of tuberculosis. Tuberculosis was frequently asymptomatic. Three patients
      had extrapulmonary tuberculosis. Chest radiographs showed residual fibrotic
      lesions in three patients and noncavitated consolidation in two patients. All of
      the patients in which the purified protein derivative test was performed were
      anergic. All patients that inadvertently underwent transplantation were cured.
      CONCLUSIONS: Aggressive management is required to prevent tuberculosis in
      transplant candidates. Patients that inadvertently undergo transplantation can be
      effectively treated when diagnosed early.

PMID- 15167594
TI  - Weight gain after renal transplantation is a risk factor for patient and graft
      outcome.
AB  - BACKGROUND: The present study aimed to evaluate the effect of weight gain after
      transplantation on patient and graft outcome. METHODS: Patients receiving kidney
      transplants between April 1986 and April 2001 were divided according to their
      body mass index (BMI) at 6 months after transplantation into group I, BMI less
      than 25 (normal weight); group II, BMI greater than or equal to 25 and less than
      30 (overweight); and group III, BMI greater than or equal to 30 (obese) after
      exclusion of pediatric patients (aged < or =18 years), second transplant
      recipients, those with a history of cardiovascular disease, and those with a BMI
      less than 25 and greater than 18.5 kg/m2. Six hundred fifty kidney transplant
      recipients were selected for this retrospective study. RESULTS: There was a
      statistically significant increase in the incidence of posttransplant
      hypertension, diabetes mellitus, and ischemic heart disease in the obese group.
      The incidence and frequency of acute rejection episodes were similar in the three
      groups. A trend toward decreased graft and patient survival, which reached
      significance at 5 years and 10 years, was observed in the obese group.
      CONCLUSIONS: BMI has a strong association with outcomes after renal
      transplantation independent of most of the known risk factors for patient and
      graft survival.

PMID- 15167595
TI  - Cold ischemia time, surgeon, time of day, and surgical complications.
AB  - BACKGROUND: Surgical factors are an important cause of early renal allograft loss
      and contribute to patient morbidity and mortality. The United Kingdom National
      Confidential Enquiry into Peri-operative Deaths has reported that operating out
      of normal working hours was associated with higher patient mortality because of
      inexperienced surgeons. In this study, we looked into whether operating outside
      normal working hours or the grade of the surgeon affected the incidence of
      surgical complications. We also examined the relationship between cold ischemic
      time (CIT) and likelihood of surgical complications. PATIENTS AND METHODS: We
      performed a retrospective review of 322 adult recipients who received their first
      cadaver kidney transplant in our center between January 1, 1998 and June 30,
      2001. Information on surgical complications were collected from patients'
      records. CIT, time of surgery, and grade of the operating surgeons was obtained
      from a local audit database (www.nwkta.org.) and the database held by UK
      Transplant. RESULTS: Surgical complication(s) were less likely to occur if one of
      the surgeons was a consultant (P =0.002). We found no association between cold
      storage and incidence of surgical complication(s). The median CIT was 21.30
      (range 3.3-43.5) hours, n=229, in the group without complications compared with
      21.80 (8.8-47.9) hours, n=77, for those with complications. The incidence of
      surgical complications was the same regardless of whether the operation took
      place during the day, evening, or night. CONCLUSIONS: Prolonged CIT and operating
      out of normal working hours did not increase the incidence of surgical
      complications. Presence of a consultant did, however, reduce the likelihood of a
      surgical complication occurring.

PMID- 15167596
TI  - Abo-incompatible heart transplantation in infants: the Freeman Hospital
      experience.
AB  - BACKGROUND: Incompatibility of the major blood groups A, B, and O has been an
      absolute contraindication for heart transplantation. However, because of
      immunologic immaturity, infants may have relative protection from hyperacute
      rejection and thus could undergo transplantation with ABO-mismatched organs.
      METHODS: Since January 2000, the authors have adopted a policy of considering
      infants for ABO-incompatible heart transplantation. Serum isohemagglutinin titers
      were measured before, during, and after transplantation. Two infants (3 and 2
      months old) and a 21-month-old child underwent ABO-incompatible heart
      transplantation. During cardiopulmonary bypass, plasma exchange was performed. No
      other antibody-removal procedures were performed. A routine immunosuppressive
      regimen was used, and rejection was monitored by endomyocardial biopsies. An
      additional two patients (31 and 18 months old) were worked up but were unsuitable
      for ABO-incompatible transplantation because of high isohemagglutinin titers.
      They were successfully bridged to transplantation and received heart transplants
      from ABO-compatible donors. RESULTS: All three infants with ABO-incompatible
      heart transplants are fit and well, 40 months, 30 months, and 12 months
      postoperatively. All three had serum antibodies to antigens of the donor's blood
      group before transplantation. No hyperacute rejection occurred. No morbidity
      attributable to the ABO incompatibility has been observed. CONCLUSIONS: ABO
      mismatched heart transplantation may be undertaken safely and without any short
      term adverse consequences in infants and young children in whom isohemagglutinin
      production is not yet established.

PMID- 15167597
TI  - Perioperative normovolemic anemia is safe in pediatric living-donor liver
      transplantation.
AB  - BACKGROUND: Perioperative normovolemic anemia was applied in pediatric living
      donor liver transplant (LDLT) recipients with the aim of reducing the use of
      blood products and decreasing transfusion-related risk. METHODS: The anemic state
      was allowed to occur by replacing intraoperative blood and transudate loss with
      colloid solutions and a discriminate use of packed red blood cells. When blood
      transfusion was required, the amount of blood replacement was calculated to
      target a hemoglobin level not higher than 8 to 9 g/dL. RESULTS: Forty-eight
      pediatric patients underwent LDLT. Their mean hemoglobin and hematocrit levels
      were maintained below 9 g/dL and 27%, respectively, at the end of the operation,
      at the time of extubation, postoperative days 3, 10, and 20, and at the time of
      discharge. The mean ventilatory support time was 15.7 hr, and no patient required
      reintubation. Graft function normalized within the first week posttransplant in
      all patients, and there was no documented case of acute hepatic artery
      thrombosis. All the patients were discharged with acceptable liver function, and
      98% of them remain alive to date. CONCLUSION: Routine application of
      perioperative normovolemic anemia in pediatric LDLT has allowed the sparing use
      of blood products. Approximately half of our patients (42%) did not require
      intraoperative blood transfusion; 31% of the patients went home without receiving
      any blood products except 5% albumin. There were no adverse effects with this
      maneuver, and graft function was good in all patients.

PMID- 15167599
TI  - Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are
      associated with decreased renal allograft and patient survival.
AB  - BACKGROUND: Pretransplant systemic inflammation has been associated with
      decreased renal allograft survival, and infectious agents such as cytomegalovirus
      (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a
      risk factor for decreased patient and allograft survival after cadaveric renal
      transplantation and that other factors believed to modulate systemic
      inflammation, such as dialysis modality, might act synergistically with CMV to
      decrease patient and allograft survival. METHODS: The United Network for Organ
      Sharing database was reviewed to identify all patients undergoing cadaveric renal
      transplantation in the United States from 1988 to 1997. Outcomes for CMV
      seropositive and seronegative recipients of organs from CMV seronegative donors
      were analyzed. Subgroup analysis was performed to identify any synergistic
      influence on outcome between CMV serostatus and known determinants of risk,
      including degree of human leukocyte antigen mismatch, pretransplant dialysis, and
      cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation,
      12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival
      was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P
      =0.001). In addition, this group demonstrated worse overall allograft survival
      (RR 1.05, P =0.029), although this adverse effect disappeared when patients who
      died with a functioning graft were censored. Decreased allograft survival was
      most pronounced in patients who were on hemodialysis before transplantation (RR
      1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with
      decreased patient survival. Pretransplant CMV seropositivity and hemodialysis
      have a synergistic adverse effect on graft survival, independent of patient
      mortality. Additional studies are required to define mechanisms by which
      pretransplant CMV infection and dialysis modality may contribute to decreased
      allograft survival.

PMID- 15167598
TI  - Treatment of C4d-positive acute humoral rejection with plasmapheresis and rabbit
      polyclonal antithymocyte globulin.
AB  - BACKGROUND: Alloantibody-mediated acute rejection is a major cause of renal
      allograft loss despite aggressive therapy. Patients with humoral rejection can be
      identified with high sensitivity and specificity by the presence of peritubular
      capillary C4d staining on renal biopsy and donor-specific anti-human leukocyte
      antigen antibodies. Standard therapy for acute humoral rejection (AHR) has been
      removal of donor-specific antibodies by plasmapheresis (PPH) in conjunction with
      intravenous immunoglobulin therapy. We describe a series of seven patients with
      C4d positive AHR who received combined therapy with PPH and polyclonal rabbit
      antithymocyte globulin (rATG). METHODS: PPH (1.4 volume exchange) was initiated
      on diagnosis of AHR on an alternate day basis for a mean number of 6.8
      treatments, in conjunction with rATG (0.75 mg/kg/day 5-10 days) until the serum
      creatinine returned to 120% of nadir. RESULTS: The nadir posttreatment creatinine
      was significantly lower than pretreatment creatinine (1.0+/-1.2 vs. 2+/-1.4, P
      <0.007) with only one episode of graft loss. On follow-up there was no difference
      in renal allograft survival between the AHR group and the 60 patients without AHR
      who underwent transplantation during the same period. We describe the ability of
      rATG to induce apoptosis in vitro peripheral blood and activated B cells.
      CONCLUSION: Combination therapy using PPH and rATG is an effective means of
      reversing AHR in renal allografts.

PMID- 15167600
TI  - Reasons for non-use of recovered kidneys: the effect of donor glomerulosclerosis
      and creatinine clearance on graft survival.
AB  - BACKGROUND: In 2000, the United Network for Organ Sharing/Organ Procurement and
      Transplantation Network Registry reported 540 recovered kidneys were discarded
      because of biopsy results, and 210 were discarded because of poor organ function.
      We compared the percentage of glomerulosclerosis (GS) and creatinine clearance
      (CrCl) of both discarded and transplanted cadaveric kidneys and examined their
      effect on graft survival and function. METHODS: The cohort consisted of all
      cadaveric kidneys (n= 3,444) with reported biopsy results between October 25,
      1999 and December 31, 2001. Graft survival was calculated by univariate and
      multivariate models. RESULTS: Fifty-one percent of discarded kidneys had GS of
      less than 20%, 27% had a CrCl greater than 80 mL/min, and 15% (129 kidneys) had
      both GS less than 20% and a CrCl of greater than 80 mL/min. Univariate analyses
      of kidneys with less than or equal to 20% GS revealed no difference in 1-year
      graft survival when the CrCl was greater than or less than or equal to 80 mL/min.
      When GS was greater than 20%, 1-year graft survival of kidneys with a CrCl of
      greater than 80 mL/min was significantly greater than that of kidneys with a CrCl
      of less than or equal to 80 mL/min. Multivariate results showed no significant
      difference in relative risk of graft loss with GS greater than 20% versus less
      than or equal to 20% when the CrCl was either 50 or 80 mL/min. With both GS less
      than or equal to 20% and greater than 20%, serum creatinine at 1 year was
      significantly lower in kidneys with CrCl greater 80 mL/min. CONCLUSIONS:
      Calculated donor CrCl does, and percentage GS on donor kidney biopsies does not,
      correlate well with 1-year graft survival and function, and percentage GS should
      not be used as the sole criterion for discarding recovered cadaveric kidneys.

PMID- 15167601
TI  - Classical pathway complement destruction is not responsible for the loss of human
      erythrocytes during porcine liver perfusion.
AB  - BACKGROUND: Porcine livers perfused with human blood destroy 85% of human
      erythrocytes (red blood cells [RBC]) during prolonged extracorporeal perfusion,
      raising the possibility of a complement-mediated graft-versus-host effect.
      METHODS: Isolated porcine livers were perfused with fresh human blood. Plasma
      samples were analyzed for complement production by reverse CH50 analysis and
      porcine immunoglobulin class and specificity by enzyme-linked immunosorbent assay
      (ELISA) and flow cytometry. Anti-CD59 and anti-decay accelerating factor (DAF)
      monoclonal antibody were used to investigate whether human complement regulatory
      proteins inhibit porcine complement. RESULTS: After 64 hr of perfusion of porcine
      livers with human blood, mean complement activity in the perfusate was 95% of the
      starting value and increasing, whereas perfusion in the absence of a liver showed
      a falling complement activity of 28.7%. ELISA demonstrated porcine immunoglobulin
      (Ig) G and IgM in the xenoperfused human plasma. Whereas in a previous study flow
      cytometry demonstrated porcine antibodies specific for antigens on human T
      lymphocytes, in this study, anti-human RBC antibodies were not found.
      Xenoperfused human plasma did not lyse fresh human RBC. Human complement was
      consistently more efficient at lysing porcine RBC than was porcine complement at
      lysing human RBC, and human plasma inhibited the ability of porcine plasma to
      lyse human RBC, raising the possibility of cross-species complement regulation.
      Complement regulatory proteins on human RBC were blocked using mouse monoclonal
      anti-human CD59 and DAF. Blocking CD59, but not DAF, augmented lysis of human RBC
      by porcine complement. CONCLUSIONS: Human CD59 inhibits porcine complement. The
      production of porcine complement from xenoperfused porcine livers is unlikely to
      result in clinically significant injury mediated through the classical pathway of
      complement activation.

PMID- 15167602
TI  - FTY720 mediates apoptosis-independent lymphopenia in human renal allograft
      recipients: different effects on CD62L+ and CCR5+ T lymphocytes.
AB  - BACKGROUND: The sphingolipid FTY720 (FTY), a novel immune modulator, induces
      lymphopenia and prevents allograft rejection. This study was designed to study
      the effect of FTY on lymphocyte subpopulations and apoptosis in stable renal
      allograft recipients. METHODS: Stable renal allograft recipients received a
      single oral dose of 0.25 to 3.5 mg of FTY (n= 13) or placebo (n= 3). Whole blood
      was drawn immediately before and at 4, 8, 12, 24, 72, and 96 hr after
      administration. The number of lymphocyte subpopulations, with an emphasis on
      surface markers involved in lymphocyte migration, was analyzed by flow cytometry.
      Apoptotic lymphocytes were detected following Annexin V-FITC/PI staining.
      Lymphocyte mobility was investigated in a modified Boyden chamber. RESULTS: FTY
      induced a transient lymphopenia by an apoptosis-independent mechanism. In vitro
      experiments with peripheral blood mononuclear cells (PBMC) confirmed that
      clinically relevant concentrations of FTY (0.1 microM) increased lymphocyte
      mobility, whereas only suprapharmacologic concentrations of FTY (10 microM) could
      induce apoptosis. FTY-treated patients had reversible changes in the composition
      of peripheral lymphocyte subpopulations. CD62L+ T cells decreased to the greatest
      extent (-57%). In contrast, CCR5+ T-cell counts declined only marginally (-10%).
      In vitro, treatment of PBMC with FTY (1 mM-10 microM) did not induce changes in
      the expression of these surface markers. CONCLUSIONS: The data indicate that FTY
      mediates apoptosis-independent lymphopenia in human renal allograft recipients.
      FTY-induced lymphopenia preferentially affects CD62L+ and CCR5- T-lymphocyte
      subpopulations.

PMID- 15167604
TI  - Developing a porcine transplantation model: efficient gene transfer into porcine
      vascular cells.
AB  - BACKGROUND: The pig is generally regarded as likely to be the preferred donor
      animal in xenotransplantation. Although many hurdles remain to be cleared, it
      would be useful to be able to manipulate porcine endothelium genetically, among
      other reasons, to test approaches in the modulation of inflammation. However, as
      a nondividing cell, it is less easy to manipulate. METHODS: The authors performed
      in vivo and in vitro gene transfection experiments using as an adjunct the DNA
      binding agent 4',6'-diamidino-2-phenylindole (DAPI), which protects DNA from
      degradation. RESULTS: The introduction of DAPI into a liposomal transfection
      system was able to increase in vitro transfection efficiency of both endothelial
      and vascular smooth muscle cells from the pig, even in the presence of small
      amounts of serum. This last observation encouraged the authors to use this system
      in vivo in porcine carotid arteries. In this model, the authors were also able to
      demonstrate a high degree of transfection efficiency using DAPI, which seemed to
      work by protecting DNA from degradation. CONCLUSIONS: The authors believe this
      technique may allow them to address many biological questions relating to
      intervening in vascular disease, inflammation, and immune responses in the
      context of transplantation and beyond.

PMID- 15167603
TI  - Suppression of cyclosporine a nephrotoxicity in vivo by transforming growth
      factor beta receptor-immunoglobulin G chimeric protein.
AB  - BACKGROUND: Transforming growth factor (TGF)beta is implicated in the
      pathogenesis of cyclosporine A (CsA) nephrotoxicity. We examined the efficacy of
      TGF beta receptor (R)II/immunoglobulin (Ig)G Fc, a soluble chimeric protein
      consisting of the extracellular domain of human TGF beta RII and IgG1 Fc, on CsA
      nephrotoxicity in mice. METHODS: Subcutaneous injection of CsA (25 mg/kg/d) was
      given daily to mice maintained on a low-sodium diet. On days 1 and 7, an
      expression vector carrying cDNA for either TGF beta RII/IgG Fc or beta
      galactosidase was transfected into the skeletal muscles by electroporation. At 2
      or 3 weeks of CsA administration, plasma and renal TGF beta 1 levels, and
      tubulointerstitial injury and fibrosis were evaluated. RESULTS: After 2 weeks of
      CsA administration, plasma and renal TGF beta 1 levels increased to the maximum
      and then declined toward the baseline levels. Renal TGF beta 1 mRNA remained
      elevated until 3 weeks. Tubulointerstitial alterations became appreciable in 2
      weeks and intensified by 3 weeks. At 2 weeks, the TGF beta RII/IgG Fc
      intervention abolished the increase in plasma TGF beta 1, attenuated the increase
      in renal TGF beta 1 by 50%, and markedly suppressed the histologic alterations.
      At 3 weeks, the histologic alterations remained markedly suppressed by the
      intervention, with no appreciable effects on the renal TGF beta 1 mRNA and
      protein. CONCLUSION: The introduction of TGF beta RII/IgG Fc by gene transfer
      effectively abrogated CsA-induced tubulointerstitial alterations. Suppression of
      tubulointerstitial changes was evident at 3 weeks when renal TGF beta 1 mRNA and
      protein were comparable to those with CsA alone, indicating that early anti-TGF
      beta intervention is effective in suppressing the progression of CsA
      nephrotoxicity despite persistent increases in renal TGF beta 1 expression.

PMID- 15167605
TI  - Transplanted human amniotic epithelial cells express connexin 26 and Na-K
      adenosine triphosphatase in the inner ear.
AB  - Cochlear fibrocytes are the crucial component of the inner ear homeostasis and
      its defect by various causes; GJB2 (connexin [Cx] 26) mutation, for example,
      leads to hearing loss. In the present study, we investigated the potential use of
      human amniotic epithelial cells, proposed to possess pluripotential properties,
      as a source of transplantation therapy in inner ear disease. The mRNA of the gap
      junction protein Cx26 and Na-K-adenosine triphosphatase, the immunohistologic
      expression of these proteins, and the cells' intercellular communication capacity
      were detected in vitro. Their transplantation into the guinea pig cochlea
      revealed the survival and expression of the proteins even 3 weeks after
      transplantation. Transplanted human amniotic epithelial cells were localized at
      the site where the proteins function, strongly indicating their cooperation in
      the regional potassium ion recycling. This technology suggests the therapeutic
      potential for the treatment of hearing loss.

PMID- 15167607
TI  - Oral cyclosporine but not tacrolimus reduces renal transplant blood flow.
AB  - BACKGROUND: Calcineurin inhibitors are important immunosuppressive agents, but
      cause nephrotoxicity. METHODS: Instantaneous intra-renal transplant hemodynamics
      were assessed in 22 patients using quantitative cineloop color Doppler imaging
      after dosing with microemulsion cyclosporine (CSA) or tacrolimus (TAC). RESULTS:
      CSA dosing resulted in renal hypoperfusion, with a mean relative reduction of
      43%+/-20% (range 22-76%) in maximal fractional area (MFA) of color pixels to
      nadir, compared to baseline. The mean effect occurred 1.1+/-0.9 hr (median 1 hr)
      after CSA dosing and was abrogated by calcium channel blockers (P <0.05). The
      main renal artery velocities, resistive index and small vessel perfusion were
      unchanged, suggestive of medium-sized arteries mediated vasoconstriction. In
      contrast, TAC did not alter renal vascularity (2.3+/-4.0% absolute reduction of
      MFA color pixels vs. 10.7+/-6.5% with CSA, P <0.01). CONCLUSION: CSA, but not
      TAC, induces phasic hypoperfusion of variable severity within small to medium
      sized intra-renal arteries soon after dosing, mitigated by calcium channel
      blockade.

PMID- 15167606
TI  - Intravenous immunoglobulin: a safe option for treatment of steroid-resistant
      rejection in the presence of infection.
AB  - Management of recurrent allograft rejection is a risky proposition, especially in
      the presence of infections. Both steroids and antibody therapy worsen the
      infection risk. We successfully treated steroid-resistant rejection with
      intravenous immunoglobulin (IVIG) in two patients who had concomitant infections.
      IVIG should be considered the treatment of choice for management of steroid
      resistant rejection in the presence of serious infection.

PMID- 15167608
TI  - Leflunomide therapy for cytomegalovirus disease in renal allograft recepients.
AB  - Leflunomide has excellent antiviral activity against cytomegalovirus (CMV) in
      animal models and is considerably less expensive than intravenous ganciclovir. We
      used leflunomide in four consenting renal allograft recipients with symptomatic
      CMV disease, who were unable to afford ganciclovir and would otherwise remain
      untreated. This is the first report of efficacy of leflunomide in humans with CMV
      disease. They received loading dose of 100 mg of leflunomide once daily on days 1
      3 and then 20 mg once daily for 3 months. All four patients were followed up
      three times weekly with physical examination, total leukocyte counts, blood urea
      and serum creatinine for a minimum period of 6 weeks. None of the patients showed
      drug related adverse events, alteration in cyclosporine levels, or decreased
      graft function, except one who developed leucopenia. Preliminary data presented
      suggests that leflunomide therapy for CMV disease is effective and could be used
      with careful monitoring in allograft recipients who cannot afford intravenous
      ganciclovir therapy. The duration of treatment and the role of leflunomide in
      secondary prophylaxis and in situations of ganciclovir resistance need to be
      studied further.

PMID- 15167609
TI  - Use of 18FDG-pet to discriminate between infection and rejection in lung
      transplant recipients.
AB  - 18F-fluorodeoxyglucose (18FDG) uptake measured by positron emission tomography
      (PET) allows assessment of neutrophil activity in vivo and is increased in
      patients with airway inflammation or infection. Because infection but not
      rejection elicits a highly neutrophilic response, we assessed the ability of this
      non-invasive technique to differentiate these two events in lung transplant
      recipients. 18FDG-PET was measured in 15 patients classified by clinical,
      radiologic, and pathologic criteria. 18FDG-PET signal was increased with proven
      infection but not when no infection was identified (mean [standard error of
      mean]: 8.00 [1.81] and 3.16 [0.61], respectively [P = 0.021]. Rejection alone did
      not increase the signal. These data confirm that neutrophil activation is not a
      feature of acute rejection and indicate that a high 18FDG-PET signal is
      indicative of infection but not rejection in lung transplant recipients. This non
      invasive and repeatable test could reduce the number of transbronchial biopsies
      required during episodes of breathlessness after lung transplantation.

PMID- 15167610
TI  - Azithromycin therapy for patients with bronchiolitis obliterans syndrome after
      lung transplantation.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the leading cause of late
      mortality after lung transplantation. METHODS: We added azithromycin (AZI) (250
      mg/day for 5 days, followed by 250 mg every other day) to the current
      immunosuppressive therapy in eight lung transplant recipients (mean age 36 years)
      with established BOS in an attempt to prevent further decline of the forced
      expiratory volume in 1 sec (FEV1). RESULTS: Before the administration of AZI,
      there was a gradual decline of the FEV1 (-34.4%+/-14.7%) compared with the
      patients' best postoperative values. Twelve weeks after AZI had been added, there
      was a significant increase in the FEV1 (+18.3%+/-14.6%, P <0.0001, analysis of
      variance) with an absolute increase of 328+/-305 mL. This increase persisted in
      three patients during 9 months of follow-up. CONCLUSIONS: AZI is a promising drug
      for some patients with BOS after lung transplantation. The exact mechanism of
      action is unknown at the present time.

PMID- 15167612
TI  - Seminoma nine years after cardiac transplantation.

PMID- 15167611
TI  - Characterization of human CD55 and CD59 transgenic pigs and kidney
      xenotransplantation in the pig-to-baboon combination.
AB  - New transgenic pigs expressing combinations of regulators of complement
      activation and other molecules are needed to resist xenograft hyperacute
      rejection (HAR) and to further analyze and treat xenograft rejection. Double
      transgenic pigs for human CD55 (hCD55) and human CD59 (hCD59) using the promoter
      of the human elongation factor 1 alpha gene were generated, and their kidneys
      were transplanted into nonimmunosuppressed baboons. hCD55 and hCD59 were mainly
      expressed by the endothelial cells, and these cells showed increased resistance
      to complement-mediated lysis. Baboons receiving kidneys from hCD55hCD59 pigs
      survived for 5 and 6 days, and displayed alterations in coagulation.
      Thrombocytopenia and platelet microthrombi were present within the kidneys.
      Nontransgenic kidneys showed HAR in less than 2 days. Kidneys from pigs
      expressing hCD55hCD59 displayed protection against HAR in the absence of
      immunosuppression. Rejection was associated with coagulopathy leukocyte
      infiltration and a rebound of anti-alpha Gal antibodies.

PMID- 15167613
TI  - A case report of donor to recipient transmission of severe thrombocytopenia
      purpura.

PMID- 15167614
TI  - Adenovirus in kidney transplantation: an emerging pathogen?

PMID- 15167615
TI  - Complications of protocol renal biopsy.

PMID- 15167616
TI  - Multi-organ procurement and successful multi-center allocation using rapid en
      bloc technique from a controlled non-heart-beating donor.

PMID- 15167617
TI  - Immunodynamics of basiliximab in liver allograft recipient under continuous
      hemodiafiltration.

PMID- 15167618
TI  - Intestinal cryptosporidiosis mimicking acute graft-versus-host disease following
      matched unrelated hematopoietic stem cell transplantation.

PMID- 15167619
TI  - Valganciclovir for the prophylaxis of cytomegalovirus disease in pediatric liver
      transplant recipients.

PMID- 15167621
TI  - Monitoring immunosuppressive drugs: has it a future?

PMID- 15167622
TI  - Application of gene transfer technologies to transplantation.

PMID- 15167623
TI  - Topiramate serum concentration-to-dose ratio: influence of age and concomitant
      antiepileptic drugs and monitoring implications.
AB  - The influence of age and concomitant antiepileptic drugs (AEDs) on the trough
      steady-state serum concentration of topiramate, normalized to 1 mg/kg body weight
      or concentration-to-dose ratio (TPM-CDR), was assessed using multivariate methods
      in samples from 94 epileptic patients (38 under 11 years and 56 over 11 years of
      age), most of whom were outpatients receiving either just TPM (n = 20) or TPM in
      combination with other AEDs (n = 74). Analysis of the covariance showed that the
      age of the patients was influential (P < 0.001) and also showed a difference in
      TPM-CDR between the non-inducers group (TPM or TPM + lamotrigine or valproate)
      and the inducers group (TPM + carbamazepine, phenobarbital, or phenytoin) (P <
      0.001). The TPM-CDR was 0.4 +/- 0.1 in patients under 11 years with inducers (n =
      7), 0.8 +/- 0.3 in patients over 11 years with inducers (n = 32), 1.1 +/- 0.4 in
      patients under 11 years with noninducers (n = 30), and 1.8 +/- 0.6 in patients
      over 11 years with noninducers (n = 21). A two-way analysis of the variance
      showed differences between patients under 11 years and those over 11 years (P <
      0.001), and between the noninducers and inducers groups (P < 0.001). TPM-CDR was
      nearly 50% lower in patients under 11 years than in patients over 11 years, and
      in patients with TPM + inducers than in patients with TPM or TPM + noninducers,
      in both children and adults. To achieve the same serum concentration of TPM,
      children will need double the daily dose per kilogram of TPM required by adults,
      and both children and adults taking enzyme-inducing AEDs will require double the
      dose needed by those who do not take them.

PMID- 15167624
TI  - Plasma and tissue determination of 4-methylpyrazole for pharmacokinetic analysis
      in acute adult and pediatric methanol/ethylene glycol poisoning.
AB  - Methanol and ethylene glycol poisoning may result in severe intoxication. The
      inhibition of alcohol dehydrogenase by ethanol or 4-methylpyrazole (4-MP,
      fomepizole) is fundamental to their treatment. 4-MP presents several advantages
      over ethanol therapy and has been recently approved as a specific antidote for
      both intoxications. The authors have developed a simple gas chromatographic
      method to determine blood and tissue 4-MP concentrations. This method has been
      validated for its reproducibility (between-day CV < 6.3%), sensitivity (LOD 0.2
      microg/mL), and linearity. It has been used in 4 adult patients intoxicated by
      methanol and 1 child accidentally intoxicated by ethylene glycol. 4-MP was used
      for each patient, and its blood levels were monitored every 4 hours over 2-3 days
      for pharmacokinetics purposes. In the population studied, after repeated
      administration of 10 mg/kg fomepizole, plasma 4-MP concentrations ranged from 1.4
      to 21.6 microg/mL, always above the active level of 0.8 microg/mL. The mean peak
      concentration observed in the 4 adult patients was 18.5 +/- 2.6 microg/mL and in
      the child was 18.9 +/- 2.2 microg/mL. Even though 4-MP is characterized by a dose
      dependent kinetic profile, under our conditions of dosage and blood sampling, its
      elimination better fitted a first-order kinetic model. At steady state and
      without any concomitant therapies, the mean apparent elimination half-life was
      14.5 +/- 3 hours. Elimination seemed faster in the child. A trend toward a
      progessive enhancement of the 4-MP elimination rate is suggested in the pediatric
      case, with the duration of the treatment resulting in a t(1/2) below 5 hours
      after 48 hours. One patient died, and samples of blood and hepatic tissue were
      removed simultaneously during autopsy for 4-MP analysis. Interestingly, when the
      plasma concentration was subtherapeutic (<1 microg/mL) the tissue concentration
      observed was still significant with 12 microg/g, supporting an intermittent
      scheme of administration.

PMID- 15167625
TI  - Therapeutic drug monitoring of immunosuppressant drugs in Marmara University
      Hospital.
AB  - Immunosuppressive therapy is the most crucial treatment of organ-transplanted
      patients. Both cyclosporin and tacrolimus have become a part of the standard
      immunosuppressive therapy for prevention of rejection. However, lower levels of
      these drugs are associated with insufficient therapy and eventually result in
      rejection of the organ, and, on the contrary, higher levels are associated with
      toxicity to certain organs such as liver and kidneys. Therefore, the levels of
      these drugs in body fluids should be monitored for the prevention of unwanted
      situations. In this retrospective study, the authors evaluated the 18-month
      profile of blood drug concentrations of cyclosporin and tacrolimus in patients
      admitted to the TDM Unit of the Marmara University Hospital (Istanbul, Turkey)
      between June 2000 and November 2001. A total of 578 blood samples (347
      cyclosporin and 231 tacrolimus) from 134 patients (88 for cyclosporin, 46 for
      tacrolimus) were evaluated in this period. The therapeutic trough ranges were
      accepted as 100-350 ng/mL for cyclosporin and 5-20 ng/mL for tacrolimus, and
      levels below or above the identified levels were accepted to be subtherapeutic or
      toxic. Most of the results were found within the range of therapeutic levels
      (67.48% for cyclosporin and 82.71% for tacrolimus). Subtherapeutic levels were
      found in 19.92% of all cyclosporin and 10.53% of all tacrolimus assays, whereas
      toxic levels were seen in 12.60% and 6.77% of cyclosporin and tacrolimus results,
      respectively. In conclusion, this study gives information about the TDM practice
      in institutional clinical laboratory and also indicates the importance of
      critical information such as sampling time for individual decision making in
      dosage regiment.

PMID- 15167626
TI  - Efavirenz plasma concentrations in HIV-infected patients: inter- and
      intraindividual variability and clinical effects.
AB  - Efavirenz is a drug subject to extensive metabolism, mainly by the cytochrome P
      450 isoenzyme CYP2B6, known to exhibit extensive interindividual variability. The
      aim of the present study was 2-fold: to investigate the relationship between
      plasma concentration and clinical effects of efavirenz and to investigate the
      extent of the inter- and intraindividual variability of the plasma concentration
      measurements. From an open clinic, 68 HIV-positive patients on efavirenz
      containing treatment were recruited. From each patient 1 to 5 samples were
      collected; 43 had more than 1 sample taken. Most samples were taken 10-24 hours
      after the latest dose. Efavirenz was analyzed by high-performance liquid
      chromatography with UV detection. The data were analyzed by the variance
      component model analysis of variance. Efavirenz concentrations were reproducible,
      and intraindividual variability constituted only 16% of the total variance. Thus,
      84% of the variance was attributed to interindividual variability. The incidence
      of primary treatment failure was related to low plasma concentrations with a
      geometric mean concentration of 6.1 micromol/L compared with 8.7 micromol/L in
      those responding to therapy (P < 0.05). If a cutoff of 7 micromol/L is used, 10
      of 13 failing to respond were below this level compared with 15 of 45 in those
      responding. It is concluded that efavirenz plasma concentration measurement gives
      reproducible results predictive of primary treatment failure. A lower bound for
      the therapeutic level of 7 micromol/L is proposed, and data from other authors
      suggests that an upper level of 13 micromol/L may be applied.

PMID- 15167627
TI  - Compliance with methadone-based substitutive treatment: a proposed model based on
      immunoassay urinary sample screening.
AB  - Methadone (MTD) maintenance treatment is a recognized method to reduce illicit
      opiate abuse. Because of the difficulties of collecting 24-hour urines routinely,
      the monitoring of MTD compliance is currently done with random urinary screening.
      However, monitoring of MTD compliance by random urinary screening lacks accuracy
      because of its highly variable pharmacokinetics, leading to false positive or
      negative results. This study's objective was to identify factors influencing the
      reliability of urinary screening of methadone for MTD compliance monitoring in a
      field setting involving usual care for opiate-dependent patients. In a cross
      sectional population-based study, 1981 urine samples obtained from 68 patients in
      parallel with drug dose, gender, and weight were analyzed by MTD enzyme
      immunoassay (EMIT). Urinary pH was measured, and positive threshold was
      determined experimentally by box-plot analysis. Multivariate determinants of MTD
      excretion were established with stepwise multiple regression analysis. On this
      basis, adjusted values for MTD excretion were proposed and verified with an (S)-2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) assay from independent
      urine samples that were negative or doubtful by the MTD assay. MTD excretion was
      higher in men, decreased with increased urinary pH, and increased with daily
      dosage of MTD; these factors explain 32% of the total variance of urinary MTD.
      Adjustment on these 3 variables (urinary pH, sex, daily dosage) improved the
      prediction of compliance to MTD treatment. Threshold was stable across pH values
      and in agreement with EDDP results. The influence of simple variables such as
      gender, urinary pH, and daily dosage on urinary MTD excretion could be put in
      evidence and accounted for. Adjusted values of urinary MTD are more reliable than
      the raw values for monitoring compliance to MTD treatment.

PMID- 15167628
TI  - Therapeutic drug monitoring of mirtazapine and its metabolite
      desmethylmirtazapine by HPLC with fluorescence detection.
AB  - A selective and sensitive HPLC method is described for therapeutic drug
      monitoring of the antidepressant drug mirtazapine and its active metabolite
      desmethylmirtazapine. Liquid/solid extraction with C18 cartridges was used for
      cleanup of plasma samples. The chromatographic separation was carried out on a
      phenylhexyl column. No interference from other coadministered antidepressants has
      been observed in 234 samples from 184 patients. The calibration range used was
      from 1 ng/mL to 100 ng/mL. The analytic method has proven robust and well suited
      for therapeutic drug monitoring. In addition to qualitative and quantitative
      validation data for the assay method, concentration measurements in samples from
      patients on mirtazapine therapy and the relevant dosing information are
      presented. Median drug levels after a 15-mg dose were 37 ng/mL mirtazapine and 20
      ng/mL desmethylmirtazapine. When a 60-mg dose was administered, median
      concentrations of 83 ng/mL mirtazapine and 65 ng/mL desmethylmirtazapine were
      found.

PMID- 15167629
TI  - Free mycophenolic acid should be monitored in renal transplant recipients with
      hypoalbuminemia.
AB  - The current approach for therapeutic drug monitoring in renal transplant
      recipients receiving mycophenolate mofetil (MMF) is measurement of total
      mycophenolic acid (MPA) concentration. Because MPA is highly bound, during
      hypoalbuminemia the total concentration no longer reflects the free
      (pharmacologically active) concentration. The authors investigated what degree of
      hypoalbuminemia causes a significant change in protein binding and thus
      percentage free MPA. Forty-two renal transplant recipients were recruited for the
      study. Free and total concentrations of MPA (predose, and 1, 3, and 6 hours post
      MMF dose samples) and plasma albumin concentrations were determined on day 5
      posttransplantation. Six-hour area under the concentration-time curve (AUC(0-6))
      values were calculated for free and total MPA, and percentage free MPA was
      determined for each patient. The authors found a significant relationship between
      low albumin concentrations and increased percentage free MPA (Spearman
      correlation = -0.54, P < 0.0001). Receiver operating characteristic (ROC) curve
      analysis was performed on the albumin versus percentage free MPA data. The cutoff
      value of albumin determined from the ROC analysis that differentiated normal from
      elevated percentage free MPA (defined as > or = 3%) in this patient population
      was 31 g/L. At this cutoff value albumin was found to be a good predictor of
      altered free MPA percentage, with a sensitivity and specificity of 0.75 and 0.80,
      respectively, and an area under the ROC curve of 0.79. To rationalize MMF dosing
      regimens in hypoalbuminemic patients (plasma albumin < or = 31 g/L), clinicians
      should consider monitoring the free MPA concentration.

PMID- 15167631
TI  - Feasibility and acceptance of salivary monitoring of antiepileptic drugs via the
      US Postal Service.
AB  - Salivary and serum levels of phenobarbital, carbamazepine, and phenytoin are
      closely correlated. Salivary monitoring of antiepileptic drugs has a number of
      advantages including the potential for home collection if measured levels are
      unaffected by transit in the mail. Saliva was collected from 60 adult and 42
      pediatric patients in the clinic. A control aliquot was immediately frozen, and a
      second aliquot was packaged and mailed to the laboratory. Patients were also
      asked to collect another sample at the same time on the following day and mail it
      to the laboratory. On receipt, all samples were held frozen and analyzed as a
      single batch by fluorescence polarization immunoassay. The effects of mailing,
      the duration in transit, and the season were assessed by multivariable, repeated
      measures analysis of variance. One hundred two saliva samples were collected in a
      mean of 2.6 minutes, and the mailed aliquot was received in a mean of 6.4 days.
      Two children and 3 adults (4.9% of total) preferred blood collection, but the
      rest preferred saliva collection or had no preference. There was no significant
      difference between the control sample and the clinic mailed samples for any of
      the 3 medications. There were no significant effects of the duration in transit
      or the season on reliability. Transit of saliva samples in the mail does not
      adversely affect accuracy of antiepileptic drug measurement. Patients prefer and
      can successful collect saliva samples at home. Home monitoring of salivary
      antiepileptic drug levels is a cost-effective technique that deserves additional
      study.

PMID- 15167630
TI  - Dose adjustment strategy for oral microemulsion formulation of cyclosporine:
      population pharmacokinetics-based analysis in kidney transplant patients.
AB  - The present study aims to determine the population pharmacokinetic parameters of
      cyclosporine (CsA) after multiple oral administration of the microemulsion
      formulation, Neoral, in kidney transplant patients and to propose a limited
      sampling strategy to predict AUC(0-4h) using them and the Bayesian method. The
      AUC(0-4h) is a parameter that has recently been recommended as an index for the
      dose adjustment in therapeutic drug monitoring of CsA. Blood samples were
      obtained at the trough level and at hourly intervals up to 5 hours from 125
      patients (78 male and 47 female) who were receiving Neoral twice daily, and whole
      blood concentrations of CsA were measured. The population pharmacokinetic
      parameters were estimated using the NONMEM computer program and a linear two
      compartment model with first-order absorption. The observed AUC0-4h and
      concentrations at different sampling times were compared with those computer
      predicted by the Bayesian method, using the population pharmacokinetic parameters
      and 2 or 3 concentrations from those at 0 h (C(0)), 1 h (C(1)), and 2 h (C(2))
      after administration. Typical values for the absorption rate constant (k(a)),
      elimination rate constant (k(el)), apparent volume of distribution for the
      central compartment (Vd/F), and oral clearance (CL/F) calculated by population
      pharmacokinetic analysis were 2.16 hours(-1), 0.547 hours(-1), 43.3 L, and 23.7
      L/h, respectively. The CsA concentrations predicted using either the 2-point or 3
      point sampling strategy exhibited an excellent correlation with the observed
      values (R(2) > 0.81), and accordingly, the predicted AUC(0-4h) values were in
      excellent agreement with those observed. The best predictability of AUC(0-4h) was
      found for the 3-point sampling strategy using C(0), C(1), and C(2), closely
      followed by a 2-point sampling strategy using C(1) and C(2). The present findings
      suggest that a simplified strategy based on population pharmacokinetics can
      accurately predict AUC(0-4h) from concentrations at 2 or 3 sampling time points,
      providing an excellent method for the daily dose adjustment of Neoral in routine
      clinical use for kidney transplant patients.

PMID- 15167632
TI  - Feasibility and limitations of oxcarbazepine monitoring using salivary
      monohydroxycarbamazepine (MHD).
AB  - The purpose of this study is to determine the feasibility of using 10-hydroxy
      10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum
      for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators
      identified subjects seen in neurology clinics at the University of Kentucky
      Chandler Medical Center. Patients were eligible if they agreed to participate in
      this study, were taking oxcarbazepine, and if a serum MHD concentration had been
      ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were
      collected in the clinic and frozen until analysis. Blood samples were obtained by
      phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD
      concentrations were determined by high-performance liquid chromatography in the
      Clinical Laboratory at the Cincinnati Children's Hospital Medical Center. Linear
      regression analysis was used to evaluate correlations. Saliva and blood specimens
      were collected from 28 epilepsy patients, but usable samples were obtained from
      only 23. The mean serum MHD concentration was 23.9 +/- 10.0 microg/mL, and the
      mean saliva concentration was 23.1 +/- 10.1 microg/mL. There was a significant
      positive correlation between the serum and saliva concentrations: saliva (y) =
      0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD
      concentration ratio was 0.96 +/- 0.15. The results of the current study indicate
      that the relationship between freely flowing (unstimulated) saliva and serum
      concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation
      of saliva MHD monitoring is that individuals who have difficulty producing small
      quantities of saliva or who have viscous saliva should generally be avoided for
      this type of monitoring. It is also recommended to avoid saliva collection within
      8 hours after OXC dosing to allow complete absorption and transformation of the
      parent drug.

PMID- 15167633
TI  - Effect of renal function on the pharmacokinetics of enoxaparin and consequences
      on dose adjustment.
AB  - The use of weight-adjusted enoxaparin dosage in patients with renal failure
      results in increased bleeding complications. The authors investigated the impact
      of patient-related factors such as renal function on the pharmacokinetics of
      enoxaparin. Anti-Xa activity was measured in the blood of 60 patients (74 +/- 10
      years, body weight 72 +/- 15 kg, men 60%, creatinine clearance 56 +/- 24 mL/min)
      with acute coronary syndromes receiving subcutaneous administration of
      enoxaparin. A population-based approach with limited sampling strategy was used.
      A 1-compartment model with first-order absorption and elimination best fitted the
      data. The mean clearance (CL/F) and distribution volume (V/F) were 0.72 L/h and
      6.65 L, respectively. V/F was influenced by body weight. CL/F was mainly related
      to the renal function, decreasing with increasing levels of serum creatinine, and
      lower in women than in men. The elimination half-life was thus estimated to be
      6.4 and 9.2 hours in male and female patients, respectively. The final covariate
      submodel was then: [Equation included in full-text article]. Maximal anti-Xa
      activity was predicted to rise above 1.5 IU/mL in case of mild elevation of serum
      creatinine according to gender and body weight. Renal function is the main factor
      affecting enoxaparin pharmacokinetics. In patients with decreased renal function,
      enoxaparin dose should be adjusted on the basis of body weight, serum creatinine,
      and gender to reach a target anticoagulation level assessed by maximal anti-Xa
      activity in steady-state conditions.

PMID- 15167634
TI  - Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease:
      implications for therapy.
AB  - Proper prospective pharmacokinetic studies of 6-mercaptopurine (6-MP) in
      inflammatory bowel disease (IBD) patients are lacking. As a result, conflicting
      recommendations have been made for metabolite monitoring in routine practice. The
      authors have evaluated 6-MP pharmacokinetics in IBD patients, including the
      genetic background for thiopurine methyltransferase (TPMT). Red blood cell (RBC)
      6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine ribonucleotide (6
      MMPR) concentrations were measured in 30 IBD patients at 1, 2, 4, and 8 weeks
      after starting 6-MP, 50 mg once daily. Outcome measures included mean 6-TGN and 6
      MMPR concentrations (+/- 95% confidence interval, CI95%) and their associations
      with TPMT genotype, 6-MP dose, and hematologic, hepatic, pancreatic, and efficacy
      parameters during the 8-week period. Steady-state concentrations were reached
      after 4 weeks, indicating a half-life of approximately 5 days for both 6-TGN and
      6-MMPR; the concentrations were 368 (CI95% 284-452) and 2837 (CI95% 2101-3573)
      pmol/8 x 10 RBCs, respectively. Large interpatient variability occurred at all
      time points. TPMT genotype correlated with 6-TGN concentrations (0.576, P <
      0.01), and patients with mutant alleles had a relative risk (RR) of 12.0 (CI95%
      1.7-92.3) of developing leukopenia. A 6-MMPR/6-TGN ratio less than 11 was
      associated with therapeutic efficacy. Based on this pharmacokinetic analysis,
      therapeutic drug monitoring is essential for rational 6-MP dosing.

PMID- 15167635
TI  - Frequency distribution of thiopurine S-methyltransferase activity in red blood
      cells of a healthy Japanese population.
AB  - Thiopurine S-methyltransferase (TPMT), which exhibits a genetic polymorphism,
      plays an important role in the metabolism of thiopurine drugs such as
      mercaptopurine, thioguanine, and azathioprine. To determine the frequency
      distribution of TPMT activity in 157 Japanese subjects with different TPMT
      genotypes, ie, TPMT*1/*1 and TPMT*1/*3, the authors measured levels of 6
      methylmercaptopurine formed from 6-mercaptopurine in red blood cells lysates by
      HPLC. The TPMT activities in our Japanese subjects ranged from 11.0 to 42.6
      pmol/h/mgHb. Although the mean value of TPMT activities in 6 subjects with
      TPMT*1/*3C (20.3 +/- 8.1 pmol/h/mgHb) was 25% lower than that in 151 subjects
      with TPMT*1/*1 (27.0 +/- 5.1 pmol/h/mgHb), there was overlap. The ranges of TPMT
      activity in subjects with TPMT*1/*1 and those with TPMT*1/*3C were similar. The
      median values in TPMT*1/*3C and TPMT*1/*1 individuals were 20.1 (11.0-31.2) and
      26.8 pmol/h/mgHb (15.7-42.7), respectively (Mann-Whitney U-test: median
      difference 6.7 pmol/h/mgHb, 95% CI 0-25.5, P < 0.05). This observation may have
      relevance for the use of 6-mercaptopurine and azathioprine as therapeutic agents
      in Japanese patients.

PMID- 15167636
TI  - Ritonavir decreases the nonrenal clearance of digoxin in healthy volunteers with
      known MDR1 genotypes.
AB  - Our objective was to examine the influence of ritonavir on P-glycoprotein (P-gp)
      activity in humans by characterizing the effect of ritonavir on the
      pharmacokinetics of the P-gp substrate digoxin in individuals with known MDR1
      genotypes. Healthy volunteers received a single dose of digoxin 0.4 mg orally
      before and after 14 days of ritonavir 200 mg twice daily. After each digoxin dose
      blood and urine were collected over 72 hours and analyzed for digoxin. Digoxin
      pharmacokinetic parameter values were determined using noncompartmental methods.
      MDR1 genotypes at positions 3435 and 2677 in exons 26 and 21, respectively, were
      determined using PCR-RFLP analysis. Ritonavir increased the digoxin AUC(0-72)
      from 26.20 +/- 8.67 to 31.96 +/- 11.24 ng x h/mL (P = 0.03) and the AUC(0-8) from
      6.25 +/- 1.8 to 8.04 +/- 2.22 ng x h/mL (P = 0.02) in 12 subjects. Digoxin oral
      clearance decreased from 149 +/- 101 mL/h x kg to 105 +/- 57 mL/h x kg (P =
      0.04). Other digoxin pharmacokinetic parameter values, including renal clearance,
      were unaffected by ritonavir. Overall, 75% (9/12) of subjects had higher
      concentrations of digoxin after ritonavir administration. The majority of
      subjects were heterozygous at position 3435 (C/T) (6 subjects) and position 2677
      (G/T,A) (7 subjects); although data are limited, the effect of ritonavir on
      digoxin pharmacokinetics appears to occur across all tested MDR1 genotypes.
      Concomitant low-dose ritonavir reduced the nonrenal clearance of digoxin, thereby
      increasing its systemic availability. The most likely mechanism for this
      interaction is ritonavir-associated inhibition of P-gp. Thus, ritonavir can alter
      the pharmacokinetics of coadministered medications that are P-gp substrates.

PMID- 15167637
TI  - A simple approximation for busulfan dose adjustment in adult patients undergoing
      bone marrow transplantation.
AB  - Busulfan is an alkylating agent used in preparative regimens before bone marrow
      transplantation (BMT). Busulfan concentrations in plasma, expressed as the area
      under the concentration-time curve (AUC), were reported to correlate with
      treatment outcome. Because busulfan is administered in 16 doses of 1 mg/kg every
      6 hours for 4 days, the opportunities to "correct" the dose as a consequence of
      the measured AUC are limited to the 16-dosage protocol. In the present research
      busulfan pharmacokinetics were prospectively evaluated in 27 adult patients
      treated according to the above protocol by measuring the first, second, and fifth
      dose AUC. The pharmacokinetic analysis was based on a noncompartment model for
      extravascular absorption, but calculations according to a 1-compartment model
      gave similar results. A simple mathematical approximation allowed prediction of
      the AUC of the second dose from that of the first and the busulfan concentration
      at trough. Fifteen patients had the dose adjusted at the fourth dose to obtain an
      AUC within the "therapeutic window" of 950-1500 microM-min. This procedure was
      then validated by the measurement of the fifth dose AUC. It appears that this
      simple pocket calculator method allows a rapid evaluation of the need and the
      extent of dose adjustment and proved to be a valuable tool to improve busulfan
      administration in pre BMT treatment.

PMID- 15167638
TI  - Establishment of new cloned enzyme donor immunoassays (CEDIA) for haloperidol and
      bromperidol.
AB  - The authors have developed and verified the precision and accuracy of new
      automated cloned enzyme donor immunoassays (CEDIA) for haloperidol and
      bromperidol, and cross-validations have been performed with conventional
      semiautomated EIA kits (MARKIT-M) and high-performance liquid chromatographic
      (HPLC) methods. The CEDIA method provides a quick (about 10 minutes) assay for
      haloperidol or bromperidol, requiring no serum/plasma pretreatment or
      predilution. The CEDIA haloperidol/bromperidol assay showed little or no cross
      reactivity with either their metabolites or many drugs commonly coprescribed.
      MARKIT-M revealed considerable cross reactivity values proportional to the spiked
      amounts of reduced metabolites. Precision, accuracy, recovery, and linearity
      testing for the CEDIA assay were all sufficient for clinical use. Significant
      linear correlations were found between CEDIA and HPLC in measuring haloperidol
      (CEDIA = 1.06 x HPLC + 0.869; n = 44, rs = 0.913, P < 0.001) and bromperidol
      (CEDIA = 1.06 x HPLC + 0.606; n = 56, rs = 0.914, P < 0.001) concentrations. This
      study has, therefore, demonstrated that the CEDIA assay has a quick run time with
      high precision and accuracy, and this method is a useful tool for the TDM of
      haloperidol or bromperidol.

PMID- 15167639
TI  - Electronic reporting of pelvic inflammatory disease from an emergency department.
AB  - BACKGROUND AND OBJECTIVES: Pelvic inflammatory disease (PID) is a clinically
      diagnosed condition that is preventable and underreported. We developed an
      electronic emergency department (ED) PID reporting system by using an automatic
      and secure system to send computerized clinician PID diagnoses to the state
      health department. GOAL: The goal of this study was to assess if electronic
      transmission of ED PID data could enhance the completeness and timeliness of PID
      surveillance. STUDY DESIGN: We conducted a retrospective chart review. METHODS:
      To validate electronic ED diagnoses, we reviewed charts of 157 women with 7
      clinicians' diagnoses compatible with PID. We determined which women met the
      Centers for Disease Control and Prevention (CDC) PID surveillance case definition
      and determined the positive predictive values of electronic ED diagnoses of PID.
      We compared completeness of electronic PID reporting with state sexually
      transmitted disease surveillance. RESULTS: Three diagnoses were appropriate for
      electronic PID surveillance. Information on women with these diagnoses is sent
      daily to the health department with no extra effort needed from ED clinicians.
      Less than 10% of women who met the CDC PID case definition were reported within 6
      months through conventional methods. CONCLUSIONS: Electronic ED surveillance will
      improve completeness and timeliness of PID reporting.

PMID- 15167640
TI  - Duplex real-time polymerase chain reaction assay for detection and quantification
      of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and
      cutaneous lesions.
AB  - BACKGROUND: A sensitive and specific method for detecting herpes simplex virus
      type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for
      diagnosing genital and cutaneous infections. GOAL: The goal of this study was to
      compare quantitative real-time polymerase chain reaction (qPCR) with virus
      culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A
      duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed.
      Duplicate swabs for PCR and virus culture were collected from 89 patients
      attending our sexually transmitted infection and dermatology clinic. RESULTS: The
      duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit
      was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens
      and virus was isolated in 45 (50%) cases. First-episode infections showed higher
      viral quantities with a median value of 4.2 x 10 copies per reaction compared
      with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be
      the cause of first-episode genital infections (72%), and HSV-2 of recurrent and
      atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive
      method for diagnosing genital herpes, and the duplex format is convenient for
      typing. The method increased the detection rate by 27% compared with virus
      culture.

PMID- 15167641
TI  - Clients of female sex workers in Lima, Peru: a bridge population for sexually
      transmitted disease/HIV transmission?
AB  - OBJECTIVES: The objectives of this study were to determine the prevalence of risk
      behaviors, gonorrhea, and chlamydia in clients of female sex workers, and to
      compare them with men selected from the general population. STUDY DESIGN: We
      conducted a cross-sectional study of men recruited from commercial sex venues in
      Lima, Peru from January to February 2002. Subjects answered a survey and provided
      a urine sample. RESULTS: Men reported that in the recently concluded commercial
      sex encounter, 95.8% used condoms, and 85.8% always used condoms with female sex
      workers. Only 16% reported always using condoms with their stable partners; 50.8%
      always used condoms with casual, noncommercial partners; and 59.6% always used
      condoms for homosexual anal sex. There were 8 (2%) cases of chlamydia and no
      cases of gonorrhea. CONCLUSIONS: Clients of female sex workers report high rates
      of condom use with sex workers and a low prevalence of chlamydia and gonorrhea.
      It is unlikely that they constitute a bridging population.

PMID- 15167642
TI  - Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case
      reports of three patients.
AB  - Metronidazole-resistant Trichomonas vaginalis has been reported across the United
      States. Some reports have suggested that clinically resistant cases could be
      increasing. Currently, metronidazole is the only drug available to treat
      trichomoniasis, including resistant cases. In such cases, treatment usually
      consists of giving higher and more prolonged doses of metronidazole, which
      patients are often unable to tolerate. Tinidazole, a second-generation
      nitroimidazole currently under development in the United States, has been shown
      to be an effective therapy in resistant T. vaginalis. Tinidazole appears to have
      several advantages over metronidazole, including greater in vitro potency against
      both sensitive and resistant strains of T. vaginalis, a more prolonged duration
      of action, and improved patient tolerability. This report describes the
      successful use of tinidazole in 3 cases of clinically metronidazole-resistant
      trichomoniasis.

PMID- 15167643
TI  - Relative safety of sexual lubricants for rectal intercourse.
AB  - OBJECTIVE: The current study was conducted to determine the relative safety of
      sexual lubricants for rectal use. GOAL: Our goal was to identify a sexual
      lubricant that would not damage the rectal epithelium. STUDY DESIGN: We describe
      a mouse assay to determine the degree to which lubricants cause rectal sloughing.
      We also tested lubricants for cytotoxicity and their effect on Herpes simplex
      virus (HSV-2) infection after rectal challenge. RESULTS: Of the products tested,
      Delube and KY-Plus are most likely to damage the rectal epithelium, whereas
      Viamor, Vagisil, and Astroglide would cause some degree of rectal damage. PBS,
      Carraguard, and methylcellulose were not toxic in any of the assays. CONCLUSION:
      We have developed a quantitative method to assay the degree of sloughing of the
      rectal epithelium. Using this and other techniques, we are able to predict the
      degree to which lubricants could be safe for rectal use.

PMID- 15167644
TI  - Magnetic resonance image-reversible findings in a patient with general paresis.
AB  - MATERIAL AND METHODS: We describe clinical, cerebrospinal fluid (CSF), and
      magnetic resonance imaging (MRI) findings in a patient with general paresis. MRI
      demonstrated cortical-subcortical atrophy and broad-coalescent high-intensity T2
      lesions in right frontotemporal lobes. RESULTS: After intravenous penicillin
      therapy, the size of these lesions diminished dramatically. That regression
      correlated with improvement in neuropsychologic test and CSF analysis.
      CONCLUSION: To our knowledge, this is the first case reported in the literature
      of MRI-reversible lesions in a patient with general paresis. We suggest that MRI
      is of prognostic value in patients with general paresis. Severe atrophy,
      especially in the temporal lobe, could be a marker of bad clinical outcome.

PMID- 15167645
TI  - High occurrence of simultaneous mutations in target enzymes and MtrRCDE efflux
      system in quinolone-resistant Neisseria gonorrhoeae.
AB  - BACKGROUND: Emergence of multidrug-resistant Neisseria gonorrhoeae resulting from
      new genetic mutations is a serious threat to controlling gonorrhea. GOAL: To
      determine 1) antimicrobial susceptibilities and the corresponding genetic
      mutations and 2) the role of MtrRCDE efflux system in gonococcal resistance to
      fluoroquinolones. STUDY DESIGN: Antimicrobial susceptibility testing and sequence
      analysis of gyrA, parC, and mtrR loci of 131 N. gonorrhoeae isolates from Japan.
      RESULTS: The proportion of N. gonorrhoeae strains resistant and intermediate
      resistant to antimicrobials was 25.2% and 48.9% for ciprofloxacin, 25.2% and
      30.5% for ofloxacin, 12.2% and 53.4% for penicillin; and 17.6% and 51.1% for
      tetracycline, respectively. Strains were categorized into 22 mutation profiles,
      with GyrA-S91F/ParC-D86N/MtrR-G45D being the most predominant profile. The
      frequency of mutation in gyrA, parC, mtrR, and the mtrR promoter was 71%, 47.3%,
      77.1%, and 23.7%, respectively. Seventy-one percent of strains carried mutations
      in both gyrA and mtrR. CONCLUSION: This study reports simultaneous mutations in
      fluoroquinolone target enzymes and the MtrRCDE efflux system as a fluoroquinolone
      resistant mechanism in N. gonorrhoeae.

PMID- 15167646
TI  - Early syphilis in the United States identified in corrections facilities, 1999
      2002.
AB  - BACKGROUND: Corrections facilities offer public health practitioners an
      opportunity to gain access to large numbers of persons at risk for syphilis and
      other sexually transmitted diseases. GOALS: The goals of this study were to
      estimate the number of early syphilis cases (primary, secondary, early latent)
      identified from corrections facilities from 1999 to 2002 and to determine
      characteristics of persons likely to be identified with syphilis in corrections
      facilities. STUDY DESIGN: We determined the proportion of cases identified from
      corrections facilities for the entire United States using case reports by state
      health departments to the Centers for Disease Control and Prevention (CDC). We
      calculated the proportion of cases identified in corrections facilities in the 30
      counties with the largest number of cases in 2002 and determined the male-to
      female syphilis rate ratios. RESULTS: From 1999 to 2002, there were 63,293 cases
      of early syphilis reported to the CDC, of which 61,691 (97.5%) had a known source
      of report. Of these, 7725 (12.5%) noted corrections facilities as the source of
      information. Among men, 4747 (13.0%) cases were from corrections and in women
      2974 (11.8%) of cases were. We found that counties with a higher proportion of
      cases from corrections facilities were likely to have lower male-to-female rate
      ratios (r = -0.66, P <0.001). CONCLUSIONS: A substantial proportion of early
      syphilis cases is identified from corrections facilities. Among counties with the
      largest number of cases, a higher proportion of syphilis cases was identified
      from corrections facilities in counties with higher rates of heterosexually
      transmitted syphilis.

PMID- 15167647
TI  - Still not understanding the uneven spread of HIV within Africa.

PMID- 15167648
TI  - Is condom use habit forming?: Condom use at sexual debut and subsequent condom
      use.
AB  - OBJECTIVE: The objective of this study was to assess whether using a condom at
      adolescent sexual debut is associated with an increased likelihood of subsequent
      condom use. STUDY DESIGN: A nationally representative sample was used, including
      4024 sexually active adolescents (12-18 years) from the National Longitudinal
      Study of Adolescent Health. Logistic regression was used to model the association
      of condom use at sexual debut on condom use at most recent sex (mean interval, 23
      months). RESULTS: Condom use at adolescent sexual debut was associated with a
      twofold increased likelihood of condom use during most recent sex (odds ratio,
      2.28; 95% confidence interval, 1.91-2.73). CONCLUSIONS: Among adolescents, early
      condom use is associated with an increased likelihood of subsequent condom use.

PMID- 15167649
TI  - Surveillance for repeat gonorrhea infection, San Diego, California, 1995-2001:
      establishing definitions and methods.
AB  - BACKGROUND: Persons with repeat gonorrhea (GC) infection often participate in
      sexual networks that maintain and spread GC throughout the community. However,
      there are no established methods for collecting repeat GC surveillance data that
      are needed to monitor trends and risk factors for repeat infection. GOAL: The
      goal of this study was to evaluate definitions and methods for establishing
      surveillance for repeat gonorrhea infection. STUDY DESIGN: During a 7-year period
      (1995-2001), all reported GC cases in San Diego County, California, were reviewed
      to identify persons with >2 GC infections that occurred >30 but <365 days apart.
      Various matching criteria and definitions of repeat infection were evaluated.
      RESULTS: Overall, 12,287 GC infections were reported; 509 persons accounted for
      551 episodes of repeat infection and 9.7% of all GC infections. The mean annual
      repeat GC case rate was 2.8 per 100,000 population (range, 1.5-4.1) and repeat
      cases were 4.5% of total GC (range, 2.7-5.5%). Temporal trends in both repeat
      measures mirrored the overall county reported GC case rate. Young, inner-city
      males were more likely to have reported repeat GC infection. CONCLUSION: Simple,
      uniform repeat GC measures can be used to establish a surveillance system for
      monitoring trends, risk factors, and the impact of interventions directed toward
      preventing repeat GC infections.

PMID- 15167650
TI  - Scale-free networks and sexually transmitted diseases: a description of observed
      patterns of sexual contacts in Britain and Zimbabwe.
AB  - BACKGROUND: Sexually transmitted infections spread through a network of contacts
      created by the formation of sexual partnerships. In physics, networks have been
      characterized as "scale-free" if they follow a power law with an exponent between
      2 and 3. OBJECTIVE: The objective of this study was to test statistically whether
      distributions of numbers of sexual partners reported from different populations
      are well described by power laws. STUDY DESIGN: Power laws and an exponential
      null model are fitted by maximum likelihood techniques to reported distributions
      of numbers of partners. Data are taken from 4 population-based surveys, 3 from
      Britain and 1 from rural Zimbabwe. RESULTS: The networks can be described by
      power laws over a number of orders of magnitude. In addition, the derived
      exponents differ significantly and meaningfully, with an "accelerating network"
      formed between men who have sex with men (MSM). CONCLUSIONS: A scale-free network
      approach provides a reasonable description of distributions of reported numbers
      of sexual partners.

PMID- 15167651
TI  - Network models and transmission of sexually transmitted diseases.

PMID- 15167652
TI  - High fear-avoiders of physical activity benefit from an exercise program for
      patients with back pain.
AB  - STUDY DESIGN: A subgroup analysis of patient outcomes from a randomized
      controlled trial comparing a Back to Fitness program with usual general
      practitioner care. OBJECTIVES: To test whether patients with high scores on
      measures of fear-avoidance and distress/depression benefit the most. SUMMARY OF
      BACKGROUND DATA: A fitness program, ongoing since the 1980s, was developed for
      use in the community and has been shown to be effective in reducing disability.
      Detailed analyses are needed to identify patient groups who benefit. Recent
      evidence points to the potentially important role of fear, distress, and
      depression. METHOD: Data from 98 patients allocated to normal general
      practitioner care and 89 patients allocated to a group exercise program were
      analyzed after categorizing baseline scores on fear-avoidance beliefs (high/low)
      and distress/depression (at risk/normal). The main outcome measure was the Roland
      Disability Questionnaire. Outcomes were compared between the intervention and
      control groups at 6 weeks, 6 months, and 12 months. RESULTS.: High fear-avoiders
      fared significantly better in the exercise program than in usual general
      practitioner care at 6 weeks and at 1 year. Low fear-avoiders did not. Patients
      who were distressed or depressed were significantly better off at 6 weeks, but
      the benefits were not maintained long-term. CONCLUSION: Patients with high levels
      of fear-avoidance beliefs could significantly benefit from the Back to Fitness
      program. The benefits of the exercise program for patients with high levels of
      distress/depression appear to be short-term only. Average attendance was only 4
      to 5 classes, which may not be sufficient for more recalcitrant cases. Further
      research is indicated.

PMID- 15167654
TI  - Morphometric study of the thoracic vertebral pedicle in an Indian population.
AB  - STUDY DESIGN: Morphometric study of the thoracic vertebral pedicular parameters
      and comparison with the previous studies in the literature. OBJECTIVES: To define
      pedicular dimensions and screw placement in the Indian population. SUMMARY OF THE
      BACKGROUND DATA: Pedicular morphometric characteristics vary in different
      population groups. Thoracic pedicular screw fixation is being used more
      frequently with the advent of better imaging methods. Because of the small size
      and close proximity to the neurovascular structures, thoracic pedicle fixation
      has little margin of safety. METHODS: T1-T12 vertebral pedicles were studied in
      18 cadavers by direct, roentgenographic, and computerized tomographic scan
      methods. The following parameters were studied: transverse diameter, transverse
      angle, sagittal diameter, sagittal angle, chord length, interpedicular distance,
      pedicle entrance point, and pedicle cortical thickness (medial and lateral).
      RESULTS.: Transverse diameter was more than 6 mm at both ends of the thoracic
      spine (T1, T2, T11, and T12). Between T3-T9 levels, it was less than 5 mm at some
      levels. The transverse angle was widest at T1 (30 degrees) and was less than 5
      degrees from T5 to T12. Pedicles were directed cephalad in the sagittal plane at
      all thoracic levels. Sagittal angle was less than 12 degrees at all thoracic
      levels. Chord length was largest at T11 (37.3 mm) and smallest at T1 and T2 (29.9
      mm). Interpedicular distance was 29 mm at T12 and 21.3 mm at T1. Medial pedicular
      cortex was thicker than lateral cortex at all levels. CONCLUSIONS: These results
      suggest that even a 4-mm screw should be used carefully at the midthoracic level;
      5-mm screw seems to be safe at upper and lower thoracic spine. Because of very
      small sagittal and transverse angle at mid and lower thoracic levels, the
      pedicular screw should be inserted along almost perpendicular line in these
      planes; 25-mm and 30-mm screw length appears to be safe at upper thoracic and
      lower thoracic levels, respectively. Pedicle entrance point lies along the
      midtrans-verse line at upper thoracic levels and along the upper border of
      transverse process at lower thoracic levels.

PMID- 15167655
TI  - Demonstration of substance P, calcitonin gene-related peptide, and protein gene
      product 9.5 containing nerve fibers in human cervical facet joint capsules.
AB  - STUDY DESIGN: Human cervical facet joint capsules were evaluated by
      immunohistochemistry. OBJECTIVES: To study the neuropeptide innervation of the
      cadaveric cervical facet joint capsules. SUMMARY OF BACKGROUND DATA: Various
      clinical and biomechanical studies indicate a role for cervical facet joint
      capsules in the etiology of neck pain. However, studies on innervation of these
      capsules are very limited. There is also a dearth of studies on the neuropeptide
      nature of this innervation. METHODS: Facet joint capsules harvested from
      unembalmed cadavers were studied by the avidin biotin peroxidase method for the
      presence of nerve fibers. Neuropeptide innervation was investigated by using
      antisera to substance P and calcitonin gene-related peptide. Antisera to protein
      gene product 9.5 (PGP 9.5), a general neuronal marker, were also used. RESULTS:
      In a study of 12 human cervical facet joint capsules, short segments of substance
      P were observed in 6 capsules, while fibers reactive to calcitonin gene-related
      peptide were demonstrated in 7 capsules. Nerve fibers immunoreactive to protein
      gene product 9.5 were also observed in 9 of the 14 capsules studied. Protein gene
      product 9.5 reactive fibers were the most extensively distributed fibers,
      observed as bundles and also as single fibers. CONCLUSIONS: An abundance of
      protein gene product 9.5 reactive nerve fibers indicates an extensive innervation
      of the cervical facet joint capsules. The presence of substance P and calcitonin
      gene-related peptide reactive nerve fibers in a population of these lends
      credence to cervical facet joint capsules as a key source of neck pain.

PMID- 15167656
TI  - Studies of human intervertebral disc cell function in a constrained in vitro
      tissue culture system.
AB  - STUDY DESIGN: This is a laboratory-based study examining a novel in vitro culture
      system for intervertebral disc tissue. OBJECTIVES: Address the hypothesis that
      "the novel culture system will preserve intervertebral disc tissue matrix and
      cell function and prevent cellular apoptosis for periods up to 21 days." SUMMARY
      OF BACKGROUND DATA: Studies of cell function in human intervertebral disc tissue
      are scarce. In vivo study of human intervertebral disc cells remains
      impracticable; in situ molecular biology in histologic sections lacks a dynamic
      dimension; and as for in vitro studies, cell culture often lacks physiologic
      relevance and explant cultures are subject to loss of tissue integrity and
      altered cell behavior. There is a biologic and therapeutic need for a
      satisfactory explant culture system for studying human intervertebral disc tissue
      in a controlled environment. METHODS: Samples of human intervertebral disc
      tissue, obtained at surgery, were examined for a number of tissue and cell
      parameters immediately after excision (controls) and following culture of tissue
      samples either in a plastic ring or unconstrained in tissue culture medium for up
      to 3 weeks. Data were compared between cultured tissue and controls. RESULTS: By
      comparison with control tissue, unconstrained explants swelled, tissue structure
      was disturbed, and there were profound changes in cell function. By contrast,
      tissue cultured in plastic rings maintained tissue structure, and after 3 weeks,
      the cellular parameters were the same as in controls. CONCLUSIONS: This is the
      first reported system to preserve cell function of human discal explants for long
      periods in tissue culture. It will be a useful tool for a wide range of
      investigations of intervertebral disc biology that have not hitherto been
      possible.

PMID- 15167657
TI  - Microfracture and changes in energy absorption to fracture of young vertebral
      cancellous bone following physiological fatigue loading.
AB  - STUDY DESIGN: Fifty-five human thoracolumbar vertebrae were randomly fatigue
      loaded and analyzed. OBJECTIVES: The purpose of this study was to explore the
      relationship between fatigue loading, trabecular microfracture, and energy
      absorption to fracture in human cadaveric thoracolumbar vertebrae. BACKGROUND:
      Although trabecular microfractures are found in vivo and have been produced by
      fatigue loading in vitro, the effect of the level of physiologic fatigue loading
      on microfracture and energy absorption has not been investigated. METHODS: Fifty
      five human thoracolumbar vertebrae (T11-L4) were randomly divided into 5 groups:
      1) control (no loading, n = 6); 2) axial compression to yield (n = 7); and 3-5)
      20,000 cycles of fatigue loading at 2 Hz (each n = 14). The level of fatigue
      loading was determined as a proportion of the yield load of Group 2 as follows:
      10% (Group 3), 20% (Group 4), and 30% (Group 5). Half of the specimens in groups
      3 to 5 were used for radiographic and histomorphometric analysis to determine
      microfracture density and distribution, whereas the other half were tested to
      determine the energy absorption to yield failure. RESULTS: No radiographic
      evidence of gross fracture was found in any of the groups following fatigue
      loading. A mean 7.5% increase in stiffness was found in specimens subject to
      cyclic loading at 10% of yield stress (Group 3). Fatigue at 20% (Group 4) and 30%
      of yield stress (Group 5) caused significantly higher (P < 0.05) increases in
      mean stiffness of 23.6% and 24.2%, respectively. Microfracture density increased
      from 0.46/mm in Group 3 to 0.66/mm in Group 4 and 0.94/mm in Group 5 (P < 0.05).
      The energy absorbed to failure decreased from 21.9 J in Group 3 to 18.1 J and
      19.6 J in Groups 4 and 5, respectively (P < 0.05). CONCLUSIONS: Fatigue loading
      at physiologic levels produced microfractures that are not detectable by
      radiography. Increased fatigue load results in an increase in microfracture
      density and decrease energy absorbed to fracture, indicating a reduced resistance
      to further fatigue loading.

PMID- 15167659
TI  - Biomechanical comparison of kyphoplasty with different bone cements.
AB  - STUDY DESIGN: Ex vivo biomechanical study. OBJECTIVES: To compare the
      biomechanical properties of isolated, fractured, osteoporotic vertebral bodies
      after treatment by kyphoplasty with one of two cements: alpha-tri-calcium
      phosphate cement (Biopex-R; Mitsubishi Materials Corp., Tokyo, Japan) or
      polymethylmethacrylate (Simplex P; Stryker-Howmedica-Osteonics, Mahwah, NJ).
      SUMMARY OF BACKGROUND DATA: Kyphoplasty and vertebroplasty typically use
      polymethylmethacrylate cements for the treatment of osteoporotic compression
      fractures. Scant information exists regarding the use of alternative cements in
      kyphoplasty. METHODS: Simulated compression fractures were created in 24
      vertebral bodies (T6-T9, L2-L5) harvested from three female cadavers. Vertebral
      bodies were assigned to one of two groups: kyphoplasty with Biopex-R or
      kyphoplasty with Simplex P. The kyphoplasty treatment consisted of inserting bone
      tamps bipedicularly into each vertebral body, inflating the tamp, and filling the
      created void with Biopex-R or Simplex P. Pretreatment and post-treatment heights
      were measured, and the repaired vertebral bodies were recompressed to determine
      posttreatment strength and stiffness values. Differences were checked for
      significance (P < 0.05) using a repeated-measures analysis of variance followed
      by Tukey's test. RESULTS: Kyphoplasty with Biopex-R restored strength in the
      lumbar and thoracic vertebral bodies. Kyphoplasty with Simplex P displayed
      significantly greater posttreatment strength than initial strength in the
      thoracic region. Vertebral bodies augmented with either cement were significantly
      less stiff than their initial conditions, except for the thoracic vertebrae
      treated with Simplex P, in which stiffness was restored. There was no significant
      difference in percentage of height restored between the cement treatments.
      CONCLUSIONS: Kyphoplasty with either cement restored initial strength. In
      general, stiffness was not restored.

PMID- 15167660
TI  - Biomechanical role of lumbar spine ligaments in flexion and extension:
      determination using a parallel linkage robot and a porcine model.
AB  - STUDY DESIGN: Porcine lumbar spine specimens were cyclically loaded in flexion
      and extension with a pure moment. The resistance to flexion and extension of the
      individual spinal elements was quantified using a sequential resection procedure.
      OBJECTIVE: To determine the biomechanical contribution of the individual
      posterior spinal ligaments, including the interconnections between the
      supraspinous and interspinous ligaments, to resisting flexion-extension moments
      applied to the lumbar spine. SUMMARY OF BACKGROUND DATA: Numerous experimental
      studies have performed repeated tests with sequential resection to determine the
      role of spinal ligaments. Most studies have not maintained the kinematics across
      trials, and therefore these studies have assessed the kinematics and kinetics of
      injured spines rather than delineating the mechanics of individual ligaments.
      METHODS: The L4-L5 motion pathway for pure moment loading (between in 16 Nm of
      flexion and 12 Nm of extension) of porcine spinal specimens was learned and
      replayed using a parallel-linkage robot. Each specimen was tested 6 times, with
      sequential resections performed as follows: intact, cut interconnections between
      the supraspinous and interspinous ligaments, supraspinous ligament removed,
      interspinous ligament removed, ligamentum flavum cut, and facet joints removed.
      The kinematic pathway was repeated for each of these tests, and, accordingly, the
      changes in loads between trials reflected the mechanics of the cut/removed
      structures. RESULTS: The interaction between the supraspinous and interspinous
      ligaments is a significant contributor to the flexion resistance of the porcine
      lumbar spine, resisting 10.5% of the peak flexion moment. This contribution is
      similar to the interspinous ligament (11.3%) and almost as large as the
      supraspinous ligament (14%) and facet joints (14.2%). The
      supraspinous/interspinous ligament complex was the largest contributor to the
      resistance of flexion motion (35.9%), followed by the intervertebral disc (25.2%)
      and the ligamentum flavum (24.7%). The only structures involved in resisting
      extension were the facet joint complexes, intervertebral disc, and possibly the
      spinous processes. CONCLUSIONS: The supraspinous/interspinous ligament complex is
      the largest contributor to resisting applied flexion moments in the porcine
      lumbar spine.

PMID- 15167661
TI  - Injury mechanisms of the cervical intervertebral disc during simulated whiplash.
AB  - STUDY DESIGN: A kinematic analysis of cervical intervertebral disc deformation
      during simulated whiplash using the whole cervical spine with muscle force
      replication model was performed. OBJECTIVES: To quantify anulus fibrosus fiber
      strain, disc shear strain, and axial disc deformation in the cervical spine
      during simulated whiplash. SUMMARY OF BACKGROUND DATA: Clinical studies have
      documented acute intervertebral disc injury and accelerated disc degeneration in
      whiplash patients, although there has been no biomechanical investigation of the
      disc injury mechanisms. METHODS: A bench-top sled was used to simulate whiplash
      at 3.5, 5, 6.5, and 8 g using six specimens. The 30 degrees and 150 degrees fiber
      strains, disc shear strains, and axial disc deformations during whiplash were
      compared with the sagittal physiologic levels. RESULTS: Increases over sagittal
      physiologic levels (P < 0.05) were first observed during the 3.5 g simulation.
      Peak fiber strain was greatest in the posterior 150 degrees fibers (running
      posterosuperiorly), reaching a maximum of 51.4% at C5-C6 during the 8 g
      simulation. Peak disc shear strain was also greatest at the posterior region of
      C5-C6, reaching a maximum of 1.0 radian due to posterior translation during the 8
      g simulation. Axial deformation at the anterior disc region exceeded physiologic
      levels at 3.5 g and above, while axial deformation at the posterior region
      exceeded physiologic limits only at C5-C6 at 6.5 g and 8 g. CONCLUSIONS: The
      cervical intervertebral discs may be at risk for injury during whiplash because
      of excessive 150 degrees fiber strain, disc shear strain, and anterior axial
      deformation.

PMID- 15167662
TI  - Geometric results of anterior cervical plate stabilization in degenerative
      disease.
AB  - STUDY DESIGN: Consecutive case retrospective computerized analysis of lateral
      radiographs. OBJECTIVES: To investigate the time evolution of the geometry of
      anterior cervical discectomy and fusion using a new computer-aided measurement
      technique. SUMMARY OF BACKGROUND DATA: Prior clinical studies have reported
      benefits and complications of anterior cervical plate stabilization, but have not
      comprehensively described changes in sagittal geometry following arthrodesis and
      plating. High fusion success rates have been reported for single-level discectomy
      and fusion, whereas multilevel procedures have demonstrated lower clinical
      success rates with increased hardware failure and pseudarthrosis rates. METHODS:
      Sagittal alignment data were collected from lateral radiographs of 51 patients
      with 52 operations for single- or multiple-level anterior cervical discectomy and
      fusion, both with and without anterior cervical plate stabilization.
      Intervertebral angulation and separation at the operated segments before surgery,
      immediately after surgery, and at long-term follow-up were compared using a
      computer-aided technique. RESULTS: Single-level anterior cervical discectomy and
      fusion with plate stabilization lost 0.9 degrees of the operatively obtained
      lordosis after surgery compared to 7.5 degrees for single-level fusions with bone
      alone (P = 0.0001). In multilevel anterior cervical discectomy and fusion, the
      bottommost level of the anterior cervical discectomy and fusion construct was
      much more prone to collapse than the remaining levels (mean bottom-level loss of
      4.0 degrees vs. mean 0.2 degrees increase at the remaining levels, P < 0.0001).
      CONCLUSIONS: Anterior cervical plate stabilization helps maintain operatively
      obtained segmental distraction and lordosis following anterior cervical
      discectomy and fusion. In multilevel procedures, this study found that
      postoperative collapse is largely localized to the bottommost level, where
      hardware failure and pseudarthrosis have been observed most often by others.

PMID- 15167663
TI  - Psychiatric morbidity in patients with chronic whiplash-associated disorder.
AB  - STUDY DESIGN: Prospective cohort with age- and gender-matched controls.
      OBJECTIVES: To compare psychiatric morbidity between two groups: patients having
      chronic symptoms after a whiplash injury and patients who recovered completely.
      SUMMARY OF BACKGROUND DATA: Psychiatric morbidity may influence the outcome of
      somatic diseases, and it has been suggested that psychological factors are often
      involved in the development of chronic symptoms after whiplash injuries, but
      there is no study assessing psychiatric morbidity in whiplash-associated disorder
      (WAD) using the Structured Clinical Interview for DSM-IV. METHODS: We studied a
      consecutive sample of 278 patients with a whiplash injury. Eighty-five had
      persisting neck pain after 1 year, and 38 of these participated in this study.
      For each patient with chronic neck pain at the 1 year follow-up, a gender- and
      age-matched recovered patient was selected from the study cohort of 278 cases.
      Psychiatric morbidity was determined using the Structured Clinical Interview for
      DSM-IV (SCID). The interview was conducted at 1 year after the accident (360
      days, SD 2 days). RESULTS: The chronic WAD group had a significantly (P < 0.05)
      greater number of diagnoses 22 (58%) according to Axis I (acquired psychiatric
      disorders) than 11 (29%) the patients who were free of symptoms. This was also
      the case for Axis I diagnoses that were reported to have occurred before the
      accident (13 [34%]vs. 3 [8%]; P < 0.01). The most common diagnosis was
      depression; indeed, the number of patients with a history of depression at the
      time of the accident was significantly higher in the group who developed chronic
      pain compared to the group who recovered (11 [29%]vs. 3 [8%]; P < 0.05).
      CONCLUSIONS: A history of psychiatric disease was more common in patients with
      chronic symptoms (chronic WAD). The dominating, retrospectively reported
      psychiatric diagnosis both before and after the accident was depression.
      Psychiatric morbidity may be a patient-related risk factor for chronic symptoms
      after a whiplash injury. The development of chronic symptoms after awhiplash
      injury seems to be associated with psychiatric vulnerability.

PMID- 15167664
TI  - Spinal position sense and disease progression in ankylosing spondylitis: a
      longitudinal study.
AB  - STUDY DESIGN: A longitudinal study of spinal position sense in 27 patients with
      mild ankylosing spondylitis (AS). OBJECTIVES: To test the hypothesis that disease
      progression in AS is associated with deficits in spinal position sense. SUMMARY
      OF BACKGROUND DATA: AS is a progressive disease that frequently leads to
      deterioration in spinal posture. The cause of postural change is unknown.
      However, pathologic involvement of spinal entheses that contain proprioceptive
      afferents suggests that impaired pro-prioception may play a role. This study
      investigates whether longitudinal changes in posture and other measures of
      disease progression are associated with deficits in spinal position sense in
      patients with mild AS. METHODS: Position sense was assessed using an
      electromagnetic movement analysis system, the 3-Space Fastrak, to determine the
      absolute error in reproducing flexed and upright spinal postures. Measurements
      were taken from sensors at T1, T7, L1, and S2 and repeated following a mean time
      interval of 13.7 months. Assessments of posture, disease activity, and function
      were also made on both occasions. RESULTS: Patients showed a significant increase
      in disease activity, and losses in spinal mobility, over time. However, no
      significant changes in spinal posture or position sense were found. Repositioning
      errors in flexed postures were < or = 3.50 at the first testing session and < or
      = 3.77 degrees at follow-up. Corresponding values for upright postures were < or
      = 2.71 degrees and < or = 2.25 degrees, respectively. CONCLUSIONS: Spinal
      position sense appears unaffected by disease progression in patients with mild
      AS. Longer follow-ups may help determine any association between disease-related
      postural change and spinal position sense in AS.

PMID- 15167665
TI  - Posterior cervicothoracic instrumentation in spine tumors.
AB  - STUDY DESIGN: We retrospectively review 32 patients who underwent posterior
      fixation for cervicothoracic junctional tumors. All patients possessed unstable
      or potential after surgery unstable spines as a result of either their tumors or
      the surgery performed. We examined cervicothoracic spine stability, maintenance
      of alignment, and associated complications. OBJECTIVES: To review our experience
      with 3 different posterior osteosynthesis systems applied to the cervico-thoracic
      junction for spinal tumors. Our review includes surgical outcomes and
      complications. The evolution through 3 different systems between 1994 and 1997
      reflects our attempts to improve accuracy in light of variable facet and pedicle
      interspaces. Our goal is not to compare the efficacy of the systems but to assess
      the efficiency of cervicothoracic facet and transpedicular screw and plate or rod
      fixation. However, we will comment on why the evolution occurred. The 3 different
      systems share a similar characteristic. Each system employs posterior cervical
      facet screw fixation and thoracic trans-pedicular screw fixation. SUMMARY OF
      BACKGROUND DATA: Spinal disorders involving the cervicothoracic junction and
      specific instrumentation to this region have been sparsely described in the
      literature. METHODS: Between June 1994 and June 2000, 32 patients underwent
      surgery for spinal tumors involving the cervicothoracic junction at our
      institution. There were 27 males and 5 females. The ages ranged from 17 to 72
      years with a mean age of 52 years. A total of 32 cervicothoracic instrumentations
      were performed. We used the R. Roy-Camille thoracolumbar plate in 20 patients,
      the cervico-thoracic plate in 8, and the Agora rod system in 4. In all, 96
      lateral mass screws were implanted from C4 to C6, 54 into C7, and 180 pedicle
      screws from T1 to T8. Nineteen patients had lung cancer with vertebral body
      invasion (Pancoast tumors), 11 had metastasis to the cervicothoracic junction, 1
      had a chondrosarcoma, and 1 had myeloma. In a first group consisting of 19
      patients, a combination of anterior and extended posterior surgical approaches
      allowed complete en bloc resection of the tumors, including all invaded
      vertebrae. Four total vertebrectomies and 15 partial vertebrectomies were
      performed. A second group of 13 patients had only posterior palliative
      stabilizing procedures with laminectomy and cervicothoracic fixation. RESULTS:
      The follow-up period varied from 3 to 54 months, average 15 months. The average
      duration of survival for patients who underwent partial or total vertebrectomy
      was 16 months (range 3-54 months). The average duration of survival for patients
      who underwent palliative decompression and stabilization was 11 months (range 5
      19 months). No changes in the sagittal alignment occurred during the immediate
      postoperative period for 30 patients. However, 2 mechanical failures occurred.
      Two patients experienced a clinically significant early increase in thoracic
      kyphosis and required revision of the posterior instrumentation. A 21-month
      minimum follow-up was available for 6 patients, in whom all implants were stable.
      We noted no screw, plate, or rod breakage in this series. No neurologic
      complications, including root impingement or spinal cord injury, or vertebral
      artery injury occurred related to screw insertion into either the thoracic
      pedicles (180 screws) or the cervical lateral masses (96 screws in C4-C5-C6 and
      54 screws in C7). CONCLUSIONS: Posterior plate or rod and screw fixation is a
      good method of treatment for cervicothoracic instability in spine tumors. Facet
      screw fixation in the cervical spine with Roy-Camille drilling technique and
      transpedicular screw fixation in the thoracic spine provides an efficacious means
      by which to stabilize the cervicothoracic junction. This stabilization technique
      was effective even in cases of high postoperative instability, such as with
      partial or total vertebrectomy. This screw-type stabilization is clinically
      effective and well documented. The evolution through 3 different systems reflects
      our attempts to improve accuracy in light of variable facet and pedicle
      interspaces. Importantly, posterior instrumentation will not interfere with
      subsequent laminectomy or more extreme surgical procedures.

PMID- 15167666
TI  - Determining the stabilizing role of individual torso muscles during
      rehabilitation exercises.
AB  - STUDY DESIGN: A systematic biomechanical analysis involving an artificial
      perturbation applied to individual lumbar muscles in order to assess their
      potential stabilizing role. OBJECTIVES: To identify which torso muscles stabilize
      the spine during different loading conditions and to identify possible mechanisms
      of function. SUMMARY OF BACKGROUND DATA.: Stabilization exercises are thought to
      train muscle patterns that ensure spine stability; however, little quantification
      and no consensus exists as to which muscles contribute to stability. METHODS:
      Spine kinematics, external forces, and 14 channels of torso electromyography were
      recorded for seven stabilization exercises in order to capture the individual
      motor control strategies adopted by different people. Data were input into a
      detailed model of the lumbar spine to quantify spine joint forces and stability.
      The EMG signal for a particular muscle was replaced either unilaterally or
      bilaterally by a sinusoid, and the resultant change in the stability index was
      quantified. RESULTS: A direction-dependent-stabilizing role was noticed in the
      larger, multisegmental muscles, whereas a specific subtle efficiency to generate
      stability was observed for the smaller, intersegmental spinal muscles.
      CONCLUSIONS: No single muscle dominated in the enhancement of spine stability,
      and their individual roles were continuously changing across tasks. Clinically,
      if the goal is to train for stability, enhancing motor patterns that incorporate
      many muscles rather than targeting just a few is justifiable.

PMID- 15167667
TI  - The role of collagen IX tryptophan polymorphisms in symptomatic intervertebral
      disc disease in Southern European patients.
AB  - STUDY DESIGN: We conducted a cross-sectional, genotyping study of intervertebral
      disc disease patients and controls. OBJECTIVES: To determine the contribution of
      COL9A2 and COL9A3 Tryptophan polymorphisms to intervertebral disc disease
      development in a genetically heterogeneous, Southern European population compared
      to previous Finnish studies. SUMMARY OF BACKGROUND DATA: The COL9A2 and COL9A3
      genes encode the alpha2 and alpha3 chains of Collagen IX. Recent Finnish studies
      suggest that a tryptophan polymorphism in the COL9A2 gene (Trp2) results in
      hereditary intervertebral disc disease, whereas a similar tryptophan mutation in
      COL9A3 (Trp3) conveys a 3-fold risk of intervertebral disc disease. METHODS: We
      studied 105 symptomatic patients with radiographically and/or surgically proven
      lumbar (98%, n = 103) or cervical (2%, n = 2) intervertebral disc disease and 102
      age-matched controls without spinal complaints from hospitals in Athens, Greece.
      Intervertebral disc disease was defined as significant disc herniation resulting
      in persistent back or leg pain. We genotyped all patients for COL9A2 and COL9A3
      allele variations using a polymerase chain reaction-based technique. RESULTS:
      None of our patients had the Trp2 allele. Consistent with previous Finnish
      findings, more Greek intervertebral disc disease cases (8.6%) than controls
      (4.9%) had at least 1 Trp3 allele, but this difference did not reach statistical
      significance (P = 0.293). The allele frequency of the Trp3 mutation was
      significantly higher among previously studied Finnish patients with
      intervertebral disc disease (12.3%) than among the Southern European patients
      with intervertebral disc disease in our study (4.3%), P = 0.001. CONCLUSIONS: The
      differences in Trp allele frequency we found between Greek and Finnish patients
      with intervertebral disc disease most likely represent true differences in
      polymorphism prevalence between the respective populations. The 2 previously
      described Trp alleles in COL9A2 and COL9A3 are likely to be less significant
      susceptibility factors for intervertebral disc disease development in Southern
      European populations.

PMID- 15167668
TI  - Preference-based quality of life measurement in patients with cervical
      spondylotic myelopathy.
AB  - STUDY DESIGN: Prospective cross-sectional observational cohort study. OBJECTIVES:
      To assess the performance of preference-based quality of life (QOL) instruments
      in patients with cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND
      DATA: Generic health status instruments (e.g., SF-36) or disease-specific health
      status measures (e.g., myelopathy scales) are typically used to measure QOL in
      patients with CSM; however, these instruments only examine a limited number of
      domains that contribute to QOL. An alternative is preference-based QOL methods,
      which integrate all factors contributing to QOL and provide a comprehensive
      individualized measure of how patients value their current health state. METHODS:
      We used four preference-based QOL methods to measure QOL in a cohort of 79
      patients with CSM: 1) visual analogue scale, 2) standard gamble, 3) time trade
      off, and 4) willingness to pay. We measured health status with the SF-36 and with
      CSM disease-specific scales devised by Nurick, Harsh, Cooper, and the Japanese
      Orthopedic Association. We used multivariate linear regression techniques to
      examine the relationships between preference-based QOL, generic health status,
      CSM disease-specific health status, and patient characteristics. RESULTS: Median
      preference-based QOL measurements for the CSM cohort were as follows: visual
      analogue scale, 0.50; standard gamble, 0.79; time trade-off, 0.75, and
      willingness to pay, $38,256. Preference-based QOL was not well explained by
      generic health status, CSM disease-specific health status, or patient
      characteristics, as shown by regression models that were unable to account more
      than 21% of the variation in preference-based QOL (R < or =0.21). CONCLUSIONS:
      Preference-based QOL in patients with CSM is poorly correlated with generic
      health status, CSM disease-specific health status, or patient characteristics.
      Studies of CSM and other spine diseases should consider incorporating preference
      based QOL measures for a fuller evaluation of the impact of spine disease and its
      treatment on QOL.

PMID- 15167669
TI  - Time-dependent surgical outcomes following cauda equina syndrome diagnosis:
      comments on a meta-analysis.
AB  - STUDY DESIGN: In this Journal Club review, we critically examine the methodology
      and results of a recently published meta-analysis describing the time dependency
      of surgical outcomes associated with cauda equina syndrome (CES) diagnosis.
      OBJECTIVES: Our objectives are to clarify the strengths, weaknesses, and
      appropriate use of statistics regarding the findings of the previous publication.
      SUMMARY OF BACKGROUND DATA: Surgical outcomes from published reports are related
      to both preoperative conditions and the time between surgery and diagnosis of
      CES. METHODS: We reexamined many of the papers that were used to create the
      surgical outcomes data set, including the publications that supplied quantitative
      information for logistic regression. Of special focus were studies that
      contributed to the "less than 24 hours from diagnosis" data. The use of
      statistical parameters such as probabilities and odds ratios to infer possible
      future outcomes is also addressed to clarify the papers' interpretations. To
      support the overall limitations of their generalized findings, we conducted a
      power analysis, which highlights the lack of statistical strength in the
      resulting conclusions. RESULTS: The results of the initial work state that an
      advantage exists in treating patients within 48 hours in comparison to treating
      them during a period greater than 48 hours after the onset of CES symptoms.
      However, the authors also state that no difference exists between the effects of
      an early surgery (less than 24 hours) compared with a subsequent period between
      24 and 48 hours after CES onset. Key elements of logistic regression and meta
      analysis are used to refute specific aspects of their methodology as well as
      their clinical interpretation regarding acute intervention. CONCLUSIONS: We
      conclude that a flawed methodology and misinterpretation of results are reported,
      understating the value of early surgical intervention.

PMID- 15167670
TI  - Augmentation of pedicle screw fixation strength using an injectable calcium
      phosphate cement as a function of injection timing and method.
AB  - STUDY DESIGN: Axial pullout tests using fresh cadaveric thoracolumbar vertebral
      bodies. OBJECTIVES: To evaluate the effect of a new injectable calcium phosphate
      cement on the axial pullout strength of both revised and augmented pedicle screws
      in comparison with polymethyl methacrylate and in terms of injection method.
      SUMMARY OF BACKGROUND DATA: Failure of pedicle screws by loosening and back out
      remains a significant clinical problem and is of particular concern for patients
      with low bone quality. Polymethyl methacrylate was shown to significantly improve
      the screw pullout strength. However, polymethyl methacrylate is known to have a
      high polymerization temperature, which may damage surrounding tissues, and a
      short handling time, and it lacks long-term biocompatibility. Bone mineral
      cements such as calcium phosphate have a longer working time, very low thermal
      effect, and are biodegradable as well as having good mechanical strength.
      Recently, new calcium phosphate cement with improved infiltration properties for
      better injectability has been introduced, but its performance in augmenting the
      pedicle screw fixation has not been tested yet. METHODS: The bone mineral
      densities of 52 vertebral bodies (T11-L5) were measured using dual-energy x-ray
      absorptiometry. In each vertebral body, a 6.5-mm-diameter and 45 +/- 5-mm-long
      pedicle screw was inserted into either the right or left pedicle, representing an
      initial intact implantation. These intact screws were pulled axially until
      failure at 10 mm/min. Following failure of the intact pedicle, 3.0 cc of cement
      was injected into the failed screw hole, representing a revision case, and the
      prepared screw hole in the contralateral intact pedicle representing an
      augmentation case. The cement was injected either to the distal tip of the screw
      hole (calcium phosphate-1 group, n = 19) or along the entire length of the screw
      hole (calcium phosphate-2 group, n = 20), and the screws were inserted. The
      cement was then allowed to cure for 24 hours at room temperature before both
      screws were pulled to failure. In 13 specimens, polymethyl methacrylate was
      injected along the entire length of the screw hole (polymethyl methacrylate
      group). Kruskal-Wallis and Mann-Whitney tests were used to compare the screw
      pullout strengths for study groups, whereas linear relationships between
      variables were assessed with scatter plots and Spearman correlation coefficients
      with a significance level of 0.05. RESULTS: Mean bone mineral densities of all
      groups were similar. A significant positive correlation was seen between bone
      mineral density and intact pullout strength. In revision, the pullout strength of
      calcium phosphate-1 was similar to that of intact, whereas the pullout strength
      of calcium phosphate-2 and polymethyl methacrylate was significantly greater than
      that of intact. In augmentation, all 3 injection methods significantly improved
      the pullout strength over intact. Injection of the calcium phosphate cement along
      the entire screw length was found to produce significantly higher pullout
      strengths than injection only at the distal tip of the screw in revision case.
      Injection of polymethyl methacrylate produced significantly higher pullout
      strengths than the injection of calcium phosphate by either method in both
      revision and augmentation. CONCLUSION: Results of this study demonstrate that the
      new calcium phosphate cement can improve the axial pullout strength of revised
      and augmented pedicle screws when injected along the entire length of the screw.
      This suggests that the injection method may be crucial for revision of failed
      pedicle screws. Considering inherent properties more favorable for in vivo
      application, such as nonexothermal polymerization and longer working time, and
      significant improvement in pullout strength, the new calcium phosphate cement may
      be a good alternative to polymethyl methacrylate for the augmentation of pedicle
      screw fixation.

PMID- 15167671
TI  - A biomechanical comparison of calf versus cadaver lumbar spine models.
AB  - STUDY DESIGN: Biomechanical flexibility tests were performed using calf and human
      cadaveric lumbar spine models to investigate the effect of anatomic differences.
      OBJECTIVES: The purpose is to determine if differences exist in biomechanical
      flexibility testing results between calf and human cadaveric spines when using
      identical methods and instrumentation. SUMMARY OF BACKGROUND DATA: Calf spines
      are commonly used in biomechanical research as a substitute for human cadaveric
      spines in an attempt to reduce expense and specimen variability. Despite
      widespread use, the validity of this model has not been thoroughly investigated.
      METHODS: Five fresh calf spines and five human cadaveric spines (L2-L5) were used
      for nondestructive biomechanical flexibility testing. Maximum moments of 6.4 Nm
      were achieved in five increments of 1.6 Nm. The rotations of L3 with respect to
      L4 were measured in 5 cases: 1) intact; 2) following partial discectomy,
      including partial laminectomy and partial facetectomy; 3) partial discectomy with
      pedicle screw instrumentation; 4) total discectomy with pedicle screw
      instrumentation; and 5) pedicle screw instrumentation with interbody graft.
      Rotational angles were normalized to the intact case to determine the stabilizing
      effect during each testing case. Data were analyzed using analysis of variance to
      determine if significant differences existed between the calf spine results and
      the human cadaveric spine results. RESULTS: In both models, motion increased
      following discectomy, decreased with instrumentation, and increased with total
      discectomy. Placement of the interbody graft decreased motion during axial
      rotation, flexion, and extension but increased lateral bending motion. A two-way
      analysis of variance revealed no significant differences in the two models during
      flexion or extension (P > 0.05), but significant differences were discovered in
      axial rotation and lateral bending (P < 0.05). CONCLUSIONS: Significant
      differences were identified in flexibility testing between calf and human
      cadaveric specimens. The calf spine model overestimated the stabilizing effect of
      instrumentation during lateral bending and underestimated stability during axial
      rotation. The extrapolation of calf spine data to the in vivo case, especially
      during axial rotation and lateral bending, should carefully consider the
      variation between these two models.

PMID- 15167672
TI  - Changes in segmental intervertebral motion adjacent to cervical arthrodesis: a
      prospective study.
AB  - STUDY DESIGN: Prospective, observational. OBJECTIVES: Quantify the changes in
      intervertebral motion adjacent to cervical arthrodesis over time. SUMMARY OF
      BACKGROUND DATA: One of the frequently acknowledged sequelae following anterior
      cervical fusion is the development of adjacent segment disease. It has been
      argued that a spine fusion transfers stress to adjacent levels and results in
      increased compensatory motion. However, there are conflicting reports as to
      whether this actually occurs, and most of these are in vitro or retrospective
      clinical studies. METHODS: Patients undergoing anterior cervical discectomy and
      fusion underwent a preoperative dynamic fluoroscopic study, followed by imaging
      at regular intervals after surgery. Imaging data were analyzed by a validated
      software system. Relative motion between adjacent vertebrae was then calculated,
      and changes in motion cephalad to the fusion followed over time. RESULTS: Twenty
      one patients were analyzed. Mean follow-up was 13 months (10-22 months).
      Intervertebral motion adjacent to the fusion changed by more than 4 degrees in 4
      of the 21 patients. However, on average, there was no difference between
      preoperative and postoperative motion for shear, flexion-extension, or vertical
      displacement at the anterior or posterior disc space. CONCLUSIONS: Although there
      was some individual variation, at a mean of 13 months following surgery, there
      was no significant change in the average junctional intervertebral motion. If
      fusion is going to affect adjacent motion, it appears that this does not
      consistently occur in the first 1 to 2 years following surgery. Additionally,
      there was no observable relationship between motion and development of
      degenerative changes during this time.

PMID- 15167673
TI  - The role of thoracoscopic spinal surgery in the management of pyogenic vertebral
      osteomyelitis.
AB  - STUDY DESIGN: Case report, operative technique. OBJECTIVES: Vertebral
      osteomyelitis is frequently associated with elderly and debilitated patients who
      have significant medical comorbidities. If surgical debridement is contemplated,
      an open anterior approach like a thoracotomy can be associated with significant
      complications in this patient population. Thus, patients with vertebral
      osteomyelitis who need surgery may benefit from minimal invasive techniques that
      avoid the complications of more extensive open approaches. We performed
      thoracoscopic spinal surgery in patients with pyogenic vertebral osteomyelitis,
      attempting to reduce the morbidity attributable to standard open thoracotomy
      surgery. METHODS: The technique and results of minimally invasive thoracoscopic
      spinal surgery for pyogenic vertebral osteomyelitis in three patients, including
      radical debridement and anterior spinal reconstruction, are presented. RESULTS:
      Radical debridement and anterior spinal reconstruction are feasible via
      endoscopic approach. Standard thoracotomy or thoracoabdominal approaches
      associated with high morbidity can be avoided, even for fusion across multiple
      levels. Conversion to open technique was not necessary in this study. There was
      no recurrence of infection or loss of reduction during the follow-up period.
      Operative time and blood loss of endoscopic technique were comparable to open
      technique. CONCLUSIONS: The cases clearly demonstrate the feasibility and
      efficacy of thoracoscopic spinal surgery in the management of pyogenic vertebral
      osteomyelitis. Debridement, decompression of the spinal canal, interbody fusion,
      and anterior spinal fixation can be performed via endoscopic approach.

PMID- 15167674
TI  - Multiple unstable cervical fractures with cord compromise treated nonoperatively:
      a case report.
AB  - STUDY DESIGN: The case of a 17-year-old boy who sustained an unusual pattern of
      multiple unstable cervical spine fractures with a spinal cord injury is
      presented. OBJECTIVE: To review the management and treatment of multiple unstable
      cervical spine fractures. SUMMARY OF BACKGROUND DATA.: Combined unstable cervical
      spine injuries are uncommon. Treatment of multiple-level cervical spine fractures
      remains controversial. METHODS: The case of a 17-year-old boy who sustained a
      ring fracture of the atlas, an atypical traumatic spondylolisthesis of the axis,
      bilateral pedicle fractures of C3 with significant anterior subluxation of C3 on
      C4, a C6 burst fracture, compression fractures of C7 and T1, and significant cord
      compression as the result of a motor vehicle accident is presented. RESULTS: The
      patient was successfully treated with an initial closed reduction using cervical
      traction for 1 week followed by placement of a cervical halo vest. The fractures
      healed successfully, and the patient regained near-normal neurologic function.
      CONCLUSIONS: Despite advances in the surgical treatment of cervical fractures and
      dislocations, nonoperative treatment with halo immobilization remains a viable
      option for selected complex injury patterns.

PMID- 15167676
TI  - Aspirin preserves neutrophil apoptosis after cardiopulmonary bypass.
AB  - The aim of this study was to test the hypothesis that ongoing aspirin therapy
      preserves neutrophil apoptosis after cardiac surgery with cardiopulmonary bypass
      (CPB) by a cyclooxygenase mechanism. Twenty patients undergoing coronary
      revascularization with CPB were enrolled in a prospective cohort study. Patients
      who had continued taking 300 mg of aspirin until the day before surgery (n = 10)
      were compared with 10 patients not taking aspirin or who had discontinued it more
      than 5 days before surgery. Neutrophils were isolated from arterial blood before
      and 6 h after surgery and apoptosis was measured after 24 h in culture using flow
      cytometry. Serum was collected and assessed for IL-6, IL-8 and PGE2 by enzyme
      linked immunoabsorbant assay. Patients were followed for clinical indices of
      sepsis for 7 days postoperatively. Spontaneous rates of neutrophil apoptosis were
      significantly reduced in postoperative compared with preoperative samples. There
      was no difference between aspirin and control preoperative neutrophil apoptosis
      rates (23.0% +/- 11.3% vs. 23.0% +/- 20.7%, P = 0.99). Postoperative neutrophil
      apoptosis was delayed in control patients (3.6% +/- 1.2% apoptosis), but this was
      significantly (P = 0.045) reversed in the aspirin-treated group (7.2% +/- 5.1%
      apoptosis). There were lower postoperative PGE2 levels in the aspirin group (136
      +/- 69 pg/mL vs. 372 +/- 210 pg/mL, P = 0.04). There was no difference in
      clinical indices of sepsis. We conclude that the delay in postoperative
      neutrophil apoptosis is significantly preserved in patients taking 300 mg of
      aspirin on the day before surgery. This was associated with greater inhibition of
      PGE2, consistent with the hypothesis that aspirin exerts its effect on apoptosis
      after CPB via a cyclooxygenase-mediated mechanism.

PMID- 15167677
TI  - Selective activation of protein kinase C delta in human neutrophils following
      ischemia reperfusion of skeletal muscle.
AB  - Circulatory neutrophils are known to be critical mediators of inflammation and
      oxidative stress during ischemia reperfusion (I/R) injury. Recent studies have
      shown an important role for protein kinase C (PKC) in neutrophil survival and
      function. Activation of specific isotypes of PKC are known to be involved in
      membrane alteration and motility, oxidative phosphorylation, and apoptosis
      modulation of neutrophils. However, the role of PKC in neutrophil responses to
      I/R in the clinical setting has not been studied. In this study, we examined the
      neutrophil activation of PKC induced by tourniquet-controlled I/R of skeletal
      muscle in humans. We found that I/R rapidly activates and translocates PKC delta,
      but not any of the classical forms of PKC (alpha or beta) from cytosol to the
      particulate fraction of neutrophils. Particulate translocation of PKC delta is
      sustained up to 4 h after reperfusion and is associated with kinase activity.
      Postreperfusion activation of PKC delta in neutrophils signals proapoptosis, but
      does not cause immediate cell death (as revealed by neutrophil morphology study
      and DNA-laddering assay). This study indicates that calcium-independent novel PKC
      delta (nPKC delta) might be predominantly involved in regulating membrane
      functions and survival of neutrophils associated with post-I/R-induced
      inflammatory oxidative stress.

PMID- 15167678
TI  - Cecal ligation and puncture versus colon ascendens stent peritonitis: two
      distinct animal models for polymicrobial sepsis.
AB  - Colon ascendens stent peritonitis (CASP) and cecal ligation and puncture (CLP),
      two animal models designed to closely mimic the clinical course of intra
      abdominal sepsis, were compared. In the past, immunomodulatory therapies
      developed in animal studies failed to be successful in humans. As a consequence,
      the established animal sepsis models were criticized. It has been proposed that
      present models had to be reevaluated, and new, clinically more relevant models
      should be evolved. CLP procedure was performed puncturing once (CLP[1]) or twice
      (CLP[2]) the ligated cecum of C57BL/6 mice. In the CASP model, a stent with
      defined diameter was surgically inserted into the ascending colon. Survival,
      bacterial load, immunohistochemistry, and serum cytokine levels were analyzed in
      the groups. Survival after CASP procedure correlated strongly with the stent
      diameter, whereas the number of punctures in CLP did not significantly change
      survival rate. Bacterial loads of peritoneal lavage, liver, and lung, as well as
      serum cytokine levels (tumor necrosis factor, interleukin 1 beta, interleukin 10)
      steadily increased from 6 to 24 h after the CASP procedure. In contrast,
      continuously low amounts of bacteria and cytokines were found in CLP mice at any
      point of time. Twenty-four hours after CLP surgery, the ligated cecum was covered
      by adhesive small bowel loops, whereas in CASP mice, the intestinal leakage was
      then still present. The CASP model mimics closely the clinical course of diffuse
      peritonitis with early and steadily increasing systemic infection and
      inflammation (systemic inflammatory response syndrome). In contrast, CLP reveals
      a model of intra-abdominal abscess formation with sustained and minor signs of
      systemic inflammation.

PMID- 15167679
TI  - Gene expression profile of inflammatory neutrophils: alterations in the
      inhibitors of apoptosis proteins during spontaneous and delayed apoptosis.
AB  - Inflammatory mediators delay neutrophil apoptosis, which contributes to the
      persistence of inflammation. The mechanisms responsible for this delay and
      resistance to Fas antibody-induced apoptosis are unknown but are dependent on
      protein synthesis. These proteins have been shown to inhibit caspase activity
      central to the induction of apoptosis. The inhibitors of apoptosis proteins have
      been shown to inhibit caspase activity and prevent apoptosis in a number of
      cellular systems. We hypothesize that the regulation of neutrophil apoptosis is
      dependent on the expression of the IAPs. c-IAP-1, c-IAP-2, and XIAP are expressed
      in the neutrophil at both the mRNA and protein level, but their relative protein
      expression is low compared with other cell types. The in vitro aging of human
      neutrophils results in their induction of apoptosis, which is associated with the
      loss of c-IAP-1 expression. The pancaspase inhibitor (zVAD-FMK) and LPS, which
      delay spontaneous apoptosis, also prevented this loss of c-IAP-1. Gene chip
      microarrays have shown that LPS increases c-IAP-1 and c-IAP-2 mRNA expression in
      neutrophils. However, this does not correspond to an increase in protein.
      Neutrophils from septic patients with delayed apoptosis show an increase in XIAP,
      with no change in cIAP-1 or cIAP-2 mRNA, demonstrating that different mechanisms
      contribute to the delay in neutrophil apoptosis. This study demonstrates that the
      loss of IAP expression may facilitate the induction of neutrophil apoptosis, and
      preventing this loss of IAP expression may represent a more significant
      contribution to delayed apoptosis rather than an increase in their expression.

PMID- 15167680
TI  - Increased susceptibility to liver injury after hemorrhagic shock in rats
      chronically fed ethanol: role of nuclear factor-kappa B, interleukin-6, and
      granulocyte colony-stimulating factor.
AB  - Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is
      associated with an increased incidence of multiorgan failure (MOF) and death;
      however, the molecular basis for this increased susceptibility is unknown. We
      previously demonstrated that production of interleukin-6 (IL-6) and granulocyte
      colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa
      B), each make essential contributions to organ injury and inflammation in a
      rodent model of controlled HS, and we proposed in this study to examine the
      hypothesis that the increased susceptibility to MOF after shock/trauma in the
      setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B
      and production of these proinflammatory cytokines. We observed increased HS
      induced liver injury 4 h after resuscitation in rats fed the ethanol-containing
      Lieber-DeCarli liquid diet for 8 weeks compared with rats fed the control liquid
      diet (3-fold increase in serum alanine aminotransferase [ALT], P = 0.008, and 2
      fold increase in focal liver necrosis, P = 0.005). The increased liver injury in
      the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B
      activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell
      production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in
      neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats.
      Thus, increased susceptibility to HS-induced liver injury in the setting of
      chronic ethanol use may be mediated, at least in part, by increased NF-kappa B
      activation resulting in increased local production of IL-6 and G-CSF and
      increased infiltration of neutrophils, which can damage liver cells directly and
      contribute to impaired sinusoidal blood flow.

PMID- 15167681
TI  - Hemodynamic and immune consequences of opiate analgesia after trauma/hemorrhage.
AB  - The regulation of compensatory hemodynamic, inflammatory, and metabolic counter
      regulatory responses to traumatic injury (trauma/hemorrhage [tx/hem]) and
      subsequent inflammatory challenges during the post-tx/hem period relies on
      balanced activation of neuroendocrine and opioid pathways. Pharmacological
      interventions during the rescue period as well as during the early post-tx/hem
      period that target these regulatory pathways can potentially affect the
      activation or efficacy of compensatory mechanisms. Their impact on mechanisms
      involved in these responses has not been well defined. We examined the impact of
      morphine and ketamine on immediate hemodynamic responses to tx/hem as well as on
      the integrity of host defense mechanisms at day 5 post-tx/hem. Morphine (10
      mg/kg), ketamine (18 mg/kg), or saline (0.3 ml) were injected intraperitoneally
      at 15 min post-tx/hem (soft tissue injury and fixed pressure hemorrhage, 40 mmHg,
      60 min) and 15 min before lactated Ringer's fluid resuscitation (LRFR, 2.4x total
      blood volume removed). Morphine, but not ketamine, produced effective and
      sustained analgesia. Morphine and ketamine impaired the rise in mean arterial
      blood pressure (MABP) during LRFR and increased 48-h mortality (2- to 3-fold).
      Morphine and ketamine markedly (40%-80%) attenuated the systemic LPS- (100
      microg/100 g body weight) induced TNF response at day 5 post-tx/hem. Morphine
      attenuated LPS-induced lung and spleen TNF expression, whereas ketamine enhanced
      spleen TNF expression but did not alter lung responses. Subsequent studies
      demonstrated that the morphine-induced impairment of the response was not due to
      altered cytokine responses during the early post-tx/hem period but that they
      could be restored and 24 h mortality could be reduced by increasing the volume of
      LRFR (2-fold). These results indicate that morphine and ketamine analgesia
      compromise the hemodynamic and host defense responses after tx/hem, directly
      affecting mortality and morbidity during the recovery period.

PMID- 15167682
TI  - Role of p38 mitogen-activated protein kinase pathway on renal failure in the
      infant rat after burn injury.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway is a proinflammatory
      signal transduction pathway for the production of cytokines and cellular response
      to stress, such as bacterial LPS or ischemia. We examined the effects of
      FR167653, a specific inhibitor of p38 MAPK, to explore the relationship between
      intestinal barrier damage and remote renal dysfunction. Immunohistochemical data
      showed the accumulation of neutrophils in the intestine after burn, and a
      horseradish peroxidase (HRP) tracer experiment showed burn-induced intestinal
      barrier damage. Our quantitative bacterial culture data demonstrated that viable
      bacteria reached the remote organs after burn and prevented the invading viable
      bacteria from using FR167653. Western blotting identified increased
      phosphorylation of p38 MAPK in the kidney after burn, and it may also have shown
      the possibility that endotoxin associated with the bacterial translocation
      enhances the activation of the p38 MAPK pathway. We blocked the intestinal
      barrier damage using FR167653, which resulted in reduced neutrophils in the
      intestine. FR167653 also prevented the increased phosphorylation of p38 MAPK in
      the kidney, which resulted in reduced neutrophils in the glomerulus and the
      reduction of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta mRNA
      in the kidneys, and, finally, prevented burn-induced renal failure. This study
      provides evidence for the hypothesis that the p38 MAPK pathway controls
      inflammatory mediators and not only improves intestinal function but also reduces
      remote renal failure after burn. We identified the pathophysiologic role of the
      p38 MAPK pathway in the development of renal failure after burn.

PMID- 15167683
TI  - Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas
      exchange.
AB  - Sepsis-induced acute lung injury is still associated with high morbidity and
      mortality. The pathophysiology is complex, and markers of injury include
      increased extravascular lung water. To evaluate the effects of the novel dual
      endothelin receptor antagonist tezosentan on endotoxin-induced changes in
      extravascular lung water and gas exchange, 16 pigs were anaesthetized and
      catheterized. Twelve animals were subjected to 5 h of endotoxemia. After 2 h, six
      of these animals received a bolus of tezosentan 1 mg kg(-1) followed by a
      continuous infusion of 1 mg kg(-1) h(-1) to the end of the experiment at 5 h.
      Conventional pulmonary and hemodynamic parameters were measured. Extravascular
      lung water was determined in these pigs after 5 h of endotoxemia, as well as in
      the four additional nonendotoxemic sham animals. Tezosentan in the current dosage
      counteracted the deterioration of lung function caused by endotoxin, as measured
      by dead space, venous admixture, and compliance. In addition, pulmonary
      hypertension was attenuated. Tezosentan had a marked effect on the endotoxin
      induced increase in extravascular lung water that was reduced to levels observed
      in nonendotoxemic sham animals. These results suggest that endothelin is involved
      in endotoxin-induced lung injury and the development of pulmonary edema. Dual
      endothelin receptor antagonism may be of value in the treatment of sepsis-related
      acute lung injury.

PMID- 15167684
TI  - Isolation of bona fide differentially expressed genes in the 18-hour sepsis liver
      by suppression subtractive hybridization.
AB  - In late sepsis, it has been established that the liver plays a major role in the
      initiation of multiorgan failure, which is the most lethal complication in
      hospitals. The molecular mechanism underlying liver failure that results from
      sepsis remains elusive. This study was undertaken to identify the bona fide
      differentially expressed genes in the 18-h septic liver by suppression
      subtractive hybridization, and the data were corroborated by Northern blot
      analysis. The differential gene expression profile renders a clue as to the genes
      involved in septic liver failure. The cecal ligation and puncture (CLP) model of
      a polymicrobial septic rat was used, with the late sepsis referring to animals
      sacrificed at 18 h after CLP. We have identified three upregulated genes (TII
      kininogen, serine protease inhibitor 2.2 [Spi2.2], and alpha 2 macroglobulin
      [alpha M]) and six down-regulated genes (hydroxysteroid dehydrogenase [3 alpha
      HSD], EST189895/mouse RNase4, bile acid-CoA-amino acid N-acyltransferase [kan
      1/rBAT], IF1, albumin, and alpha 2u-globulins [alpha 2u-G PGCL1]). Among these
      genes, the 3 alpha HSD and kan-1/rBAT are involved in bile acid metabolism. The
      IF1 plays a crucial role in any disease that involves ATP hydrolysis by F1F0
      ATPase. The alpha 2M, TII-kininogen, and Spi2.2 are protease inhibitors. The
      functions of the alpha 2u-G PGCL1 and EST189895/mouse RNase4 genes are unknown.
      The present results suggest that the roles of disturbance of bile acid
      metabolism/synthesis and the abolishment of ATP production may contribute to
      liver failure during late sepsis.

PMID- 15167685
TI  - Arterial baroreflex function determines the survival time in lipopolysaccharide
      induced shock in rats.
AB  - Lipopolysaccharide (LPS) mimics many of the effects of septic shock. LPS-induced
      death has been attributed to systemic hypotension, hyporeactiveness to
      vasoconstrictors, metabolic acidosis, and organ damage. However, there is no
      research directed to the involvement of the baroreflex sensitivity (BRS) in LPS
      induced death. The purpose of this study was to evaluate the effect of BRS on the
      survival time after lethal LPS challenge. Four groups of rats were used. Each rat
      received an equivalent dose of intravenous LPS (50 mg/kg). It was found that the
      anesthetized sinoaortic-denervated (SAD) rats (representative of the lowest BRS,
      BRS = 0.022 +/- 0.015 ms/mmHg) survived the shortest time (36 +/- 11.1 min). The
      conscious SAD rats (BRS = 0.198 +/- 0.035 ms/mmHg) and the anesthetized sham
      operated rats (BRS = 0.304 +/- 0.072 ms/mmHg) were alive a relatively long time
      (101 +/- 11.5 min and 110 +/- 12.4 min, respectively). The conscious sham
      operated rats (BRS = 0.943 +/- 0.097 ms/mmHg) survived the longest time (148 +/-
      6.5 min). These results demonstrated that arterial baroreflex function determined
      the survival time in the LPS-induced lethal shock.

PMID- 15167686
TI  - Kupffer cell-depleted rats have a diminished acute-phase response following major
      liver resection.
AB  - Partial hepatectomy (PH)-induced Kupffer cell (KC) activation results in a rapid
      release of cytokines inducing the acute-phase response (APR). This study was done
      to evaluate the role of Kupffer cells (KCs) in the course of the APR following PH
      and a consecutive endotoxin challenge. KC depletion was performed in rats by i.v.
      administration of 1 mL liposome-encapsulated dichloromethylene diphosohonate
      (Cl2MDP). Control rats received 1 mL NaCl 0.9%. Forty-eight hours later, PH was
      performed. At 24 h after PH, rats were randomized to receive either 1 mL NaCl
      0.9% (saline) or 50 microg/kg LPS i.v. in 1 mL. Animals were sacrificed at 4 h
      after LPS or saline infusion. The APR was determined by measuring hepatic gene
      expression of alpha 2-macroglobulin, alpha 1-acid glycoprotein, and IL-6 and
      expression of hepatic albumin. The APR was significantly depressed in KC-depleted
      rats. Despite increased IL-6 mRNA synthesis in response to low-dose LPS, no
      enhancement of acute-phase protein synthesis (APP) was found in KC-depleted rats.
      Hepatic failure was most profound in KC-depleted rats, as indicated by elevated
      plasma levels of liver transaminases and ammonia. We conclude that after PH, KC
      function in the remnant liver is important for the acute-phase reaction and
      reduces endotoxin-induced hepatocyte damage.

PMID- 15167687
TI  - Increased lymphoid tissue apoptosis in baboons with bacteremic shock.
AB  - The molecular mechanisms of immune cell apoptosis during sepsis remain unclear.
      Two young adult baboons (Papio sp.) received a lethal dose of live Escherichia
      coli and were sacrificed at either 16 (for animal welfare concerns) or 24 h post
      septic shock. An additional baboon, which received no bacteria, served as a
      control. Necropsy was performed immediately with subsequent immunohistochemical
      staining of lymphoid tissue. Immunohistologic analysis of tissues from the septic
      baboons revealed marked systemic lymphocyte apoptosis occurring in all lymphoid
      tissues examined. Focally, pyknotic and karyorrhectic lymphocytes demonstrated
      activation of a mitochondrial-dependent cell death pathway (active caspase 9 and
      apoptosis-inducing factor). Other regions demonstrated apoptotic lymphocytes with
      activation of a death receptor-dependent cell pathway (Fas ligand). Thus, we have
      demonstrated for the first time in primates that overwhelming gram-negative
      bacteremia produces an early and profound lymphocyte death that occurs through
      multiple cell death pathways. Bacteremic shock in the baboon may be an
      appropriate model for studying experimental therapies aimed at blocking
      lymphocyte apoptosis because their response appears comparable to humans dying
      from sepsis.

PMID- 15167688
TI  - Splanchnic metabolism during gut ischemia and short-term endotoxin and
      hemorrhagic shock as evaluated by intravasal microdialysis.
AB  - The splanchnic area is of considerable interest in different types of shock. To
      characterize the metabolic changes in the splanchnic region in response to
      different types of shock we used a model where shock-induced metabolic changes in
      the splanchnic region were studied by the use of intravasal microdialysis. 23
      anesthetized domestic pigs were randomized into four groups: Group I, serving as
      controls (n = 5); Group II, mesenteric ischemia for 180 followed by 120 min of
      reperfusion (n = 5); Group III, endotoxin shock for 5 h (n = 5); and Group IV,
      hemorrhagic shock for 180 min followed by re-transfusion of shed blood (n = 8).
      Microdialysis catheters were placed in the left femoral artery, portal vein and a
      small ileal mesenteric vein. Samples of the perfusate were continuously collected
      in micro-vials and analyzed for glucose, lactate, pyruvate and glycerol. In gut
      ischemia and endotoxin shock the outflow-pattern of lactate, lactate/pyruvate
      ratio and glucose in the mesenteric vein differed significantly from controls and
      hemorrhage whereas an increase in glycerol was only noted in the ischemic group.
      The most prominent differences were detected in lactate/pyruvate ratio, a marker
      of tissue ischemia with the most pronounced changes during mesenteric
      ischemia/reperfusion. During endotoxin shock increases in microdialysate
      metabolites were only noted in the splanchnic region suggesting a specific
      vulnerability in the region. Studying the lactate/pyruvate ratio may provide
      additional information when interpreting increased blood lactate levels. In
      addition glycerol may prove to be a useful marker of splanchnic ischemia.
      Intravasal microdialysis represents a potentially useful method for monitoring
      regional metabolic events.

PMID- 15167689
TI  - No association of the SCA1 (CAG)31 allele with Huntington's disease, myotonic
      dystrophy type 1 and spinocerebellar ataxia type 3.
AB  - Trinucleotide repeat expansions are the underlying mutation in several
      neurodegenerative and neuromuscular disorders including at least eight
      spinocerebellar ataxias (SCA). The molecular mechanisms of repeat expansion are
      as yet insufficiently understood. Recently, an association of the SCA1 (CAG)31
      repeat allele with Huntington's disease and myotonic dystrophy type 1 was
      described. These findings implicate a possible role of the SCA1 (CAG)31 allele in
      other triplet diseases. We analyzed the SCA1 CAG repeat length in a large sample
      of Huntington's disease (n=182), myotonic dystrophy type 1 (n=64) and SCA3 (n=31)
      patients. In none of these groups was a significant association with the 31
      repeat allele found. Our findings do not support the hypothesis that this allele
      is involved in the etiology of trinucleotide expansion.

PMID- 15167690
TI  - Monocyte chemoattractant protein-1 promoter -2518 polymorphism and schizophrenia
      in the Korean population.
AB  - The purpose of the present study was to investigate the association between the
      monocyte chemoattractant protein-1 (MCP-1) promoter -2518 polymorphism and
      schizophrenia. One hundred and twenty-three schizophrenic inpatients and 114
      healthy controls participated in this study. Genotyping was performed by
      polymerase chain reaction-restriction fragment length polymorphism. Genotype and
      allele distributions in patients with schizophrenia were not significantly
      different from those of the controls. However, distributions of genotypes and
      alleles were marginally different when considering subjects with positive and
      negative symptomatology. The present study therefore calls for further studies on
      the potential role of the MCP-1 promoter -2518 polymorphism in clinical
      heterogeneity of schizophrenia.

PMID- 15167691
TI  - Identification of genetic variants in the neuronal form of tryptophan hydroxylase
      (TPH2).
AB  - OBJECTIVE: We screened the complete protein coding sequence of the newly
      identified neuronal form of tryptophan hydroxylase (TPH2) for genetic variants.
      METHODS: Genomic DNA samples from 24 African-Americans and 24 Caucasian-Americans
      in the Coriell human variation collection were screened by denaturing high
      performance liquid chromatography followed by sequencing. RESULTS: We identified
      a number of genetic variants in both the coding and exon-flanking intronic
      sequences. Only one variant was identified that predicts a structural change in
      the TPH2 protein, and this was seen in only one out of 96 chromosomes.
      CONCLUSIONS: The gene for TPH2 contains a number of polymorphisms that might
      serve as useful markers for association analyses of complex behavioral phenotypes
      or as actual risk factors. Structural polymorphisms are extremely rare in TPH2
      and cannot therefore act as substantial risk factors for behavioral disorders in
      African-American and Caucasian populations.

PMID- 15167692
TI  - Enhanced APOE2 transmission rates in families with autistic probands.
AB  - We have previously described linkage/association between reelin gene
      polymorphisms and autistic disorder. APOE also participates in the Reelin
      signaling pathway, by competitively antagonizing Reelin binding to APOE receptor
      2 and to very-low-density lipoprotein receptors. The APOE2 protein variant
      displays the lowest receptor binding affinity compared with APOE3 and APOE4. In
      this study, we assess linkage/association between primary autism and APOE alleles
      in 223 complete trios, from 119 simplex Italian families and 44 simplex and 29
      multiplex Caucasian-American families. Statistically significant disequilibrium
      favors the transmission of epsilon2 alleles to autistic offspring, over epsilon3
      and epsilon4 (allele-wise transmission/disequilibrium test [TDT], chi2 = 6.16, 2
      degrees of freedom [d.f.], P<0.05; genotype-wise TDT, chi2 = 10.68, 3 d.f.,
      P<0.05). A novel epsilon3r allele was also discovered in an autistic child and
      his mother. Autistic patients do not differ significantly from unaffected
      siblings (allele-wise TDT comparing autistic patients versus unaffected sibs,
      chi2 = 1.83, 2 d.f., P<0.40, not significant). The major limitation of this study
      consists of our small sample size of trios including one unaffected sibling,
      currently not possessing the statistical power necessary to conclusively
      discriminate a specific association of epsilon2 with autism, from a distorted
      segregation pattern characterized by enhanced epsilon2 transmission rates both to
      affected and unaffected offspring. Our findings are thus compatible with either
      (a) pathogenetic contributions by epsilon2 alleles to autism spectrum
      vulnerability, requiring additional environmental and/or genetic factors to yield
      an autistic syndrome, and/or (b) a protective effect of epsilon2 alleles against
      the enhanced risk of miscarriage and infertility previously described among
      parents of autistic children.

PMID- 15167693
TI  - Genome scan of Tourette syndrome in a single large pedigree shows some support
      for linkage to regions of chromosomes 5, 10 and 13.
AB  - OBJECTIVES: To localize genes influencing the susceptibility to Gilles de la
      Tourette syndrome (GTS) and associated chronic multiple tics (CMT). METHOD: A
      single, large, multiple affected pedigree containing 35 subjects diagnosed with
      GTS and a further 14 with CMT was genotyped for markers spanning the autosomes.
      Linkage analysis was carried out using classical lod score analysis and model
      free lod score analysis. All markers were subjected to two-point analysis, and
      markers producing a two-point result significant at P<0.005 were subjected to
      three-point analysis using adjacent markers. RESULTS: The following markers
      produced at least one result significant at 0.005 using two-point analysis:
      D5S1981, D5S2050, D10S591, D10S189, D13S217, and D14S288. Three-point analysis
      with D5S2050 and D5S400 produced a lod of 2.9 with CMT. Three-point analysis of
      D10S591 and D10S189 produced lods of 1.9 with GTS and CMT. Three-point analysis
      of D13S217 and D13S171 produced a lod of 2.7 with GTS. No single haplotype
      appeared to account for the majority of cases within the pedigree. CONCLUSIONS:
      It seems likely that more than one susceptibility allele is present in the
      pedigree. Although none of the three positive regions is conclusively implicated,
      it seems probable that at least one contains a susceptibility locus. We recommend
      that association-based studies be carried out in these three regions to produce
      further evidence for a localization and to carry out fine-mapping.

PMID- 15167694
TI  - Association study of personality factors and the Asn40Asp polymorphism at the mu
      opioid receptor gene (OPRM1).
AB  - INTRODUCTION: This study examined whether a functional polymorphism (A118G) in
      the gene encoding the mu-opioid receptor protein, which causes an Asn40Asp
      substitution in the receptor's extracellular domain, is associated with
      personality factors, as defined by the Five-Factor Model of Personality. METHODS:
      Healthy subjects (n=446) and substance-dependent subjects (n=335) underwent a
      diagnostic interview, completed the NEO Five-Factor Inventory and provided a
      blood sample for genotyping. Controlling for demographic features and substance
      dependence diagnosis, analyses examined the allelic association of Asn40Asp with
      the five personality dimensions. RESULTS: There was no evidence for allelic
      association with any of the five personality dimensions. CONCLUSION: These
      findings fail to support the hypothesis that Asn40Asp alleles moderate the
      development of personality dimensions, as measured by the Five-Factor Model.

PMID- 15167695
TI  - Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in
      patients with schizophrenia and normal controls.
AB  - BACKGROUND: In patients with schizophrenia, the percentage of patients with
      diabetes has been found to be twice that of the normal population. The risk
      factors for this higher rate are unknown, although dietary, lifestyle, and
      genetic factors have all been suggested. Recently, a polymorphism (-759C/T) in
      the serotonin 2C (5HT2C) receptor promoter region has been associated with the
      development of diabetes in a normal control population, with the frequency of the
      T allele being higher in subjects without diabetes. AIM: To determine whether the
      distribution of the -759C/T polymorphism of the 5HT2C receptor is different among
      patients with schizophrenia and normal controls. METHODS: DNA from 100 patients
      with schizophrenia and 81 normal controls were analyzed for the 5HT2C receptor 
      759C/T polymorphism to determine its allelic frequencies in these two groups.
      RESULTS: Using a chi-squared analysis, no statistical differences in the
      distribution of C alleles and T alleles were found between the two groups
      (P=0.2931). CONCLUSIONS: Patients with schizophrenia have a higher risk for
      developing diabetes than the general population. We did not find a higher
      distribution of the -759T allele of the 5HT2C receptor in normal controls
      compared with in patients with schizophrenia. This suggests the higher prevalence
      of diabetes in schizophrenia is not due to this polymorphism.

PMID- 15167696
TI  - Putative association of polymorphism in the mannose 6-phosphate receptor gene
      with major depression and Alzheimer's disease.
AB  - The endosomal lysosomal system might play a role in Alzheimer's disease, but its
      impact in major depression is unknown. The expression of the cation-dependent
      mannose 6-phosphate receptor (CD-MPR) is increased in Alzheimer's disease and the
      CD-MPR gene is located next to a region on chromosome 12 possibly linked to
      Alzheimer's disease. We investigated a C/T polymorphism in the CD-MPR gene in 188
      Alzheimer's disease patients, in a control sample of 193 patients with major
      depression, as hospitalized controls, and in 259 healthy controls. We examined
      the interaction of the CD-MPR polymorphism with the putative risk factor for
      Alzheimer's disease, the cathepsin D T-allele. No significant association of the
      CD-MPR C-allele with Alzheimer's disease was observed. However, exploratory data
      analysis revealed an increased frequency of the CD-MPR C-allele in patients with
      major depression; thus, the C-allele may be a risk factor for depression. Gene
      location and function of the CD-MPR suggest an involvement in Alzheimer's
      disease; however, we could not find an association of the CD-MPR polymorphism
      with Alzheimer's disease. Since exploratory data suggest an involvement of the
      endosomal lysosomal system in major depression, further studies are warranted to
      investigate the biological role of the CD-MPR in major depression.

PMID- 15167697
TI  - Linkage analysis in bipolar pedigrees adds support for a susceptibility locus on
      21q22.
AB  - Several studies provide suggestive evidence of a susceptibility locus for bipolar
      disorder at chromosome 21q22-23. In an attempt to replicate these findings, we
      have analyzed linkage to 11 polymorphic markers from this region in 18 Bulgarian
      pedigrees with affective disorder. Two-point linkage analysis under assumption of
      homogeneity and a dominant model with reduced penetrance produced modest positive
      values for some of the markers tested under a 'narrow' phenotype definition,
      including bipolar I and II, and schizoaffective disorder. The maximum two-point
      score (lod=1.76, theta=0.00) was at marker D21S1919. Non-parametric linkage
      analysis under the same phenotype model, yielded positive NPLall values (P<0.05)
      over the region between markers D21S211 and D21S416, with a peak at D21S1252 (NPL
      Zall=2.32, P=0.0003). The multipoint lod score (GENEHUNTER) reached a suggestive
      value for linkage (lod=2.10) also at marker D21S1252. The results under a
      recessive model were completely negative. These data add to the evidence for the
      existence of a susceptibility locus for bipolar affective disorder on chromosome
      21q22.

PMID- 15167698
TI  - Analysis of the -1438 G/A polymorphism of the 5-HT2A serotonin receptor gene in
      bulimia nervosa patients with or without a history of anorexia nervosa.
AB  - A single nucleotide polymorphism (-1438 G/A) located 1438 base pairs upstream of
      the consensus start site of the 5-HT2A receptor gene has been reported. The
      hypothesis that this gene polymorphism may be a susceptibility factor in bulimia
      nervosa was explored in a female population of purgative bulimics. Bulimia
      nervosa patients who have suffered preceding anorexia nervosa episodes formed the
      so-called previous anorexia nervosa bulimic patient group. At variance with some
      previous reports, when the frequency distribution of genotypes and alleles was
      compared in patients and controls, no differences were detected regardless of
      whether the bulimia nervosa patients had suffered prior anorexia nervosa
      episodes.

PMID- 15167699
TI  - Serotonin transporter promoter gene polymorphism and long-term outcome of
      antidepressant treatment.
AB  - OBJECTIVE: This study investigates the relationship between the serotonin
      transporter linked polymorphic region (5-HTTLPR) and the long-term outcome of
      antidepressant treatment. METHODS: One hundred and twenty-eight patients with
      major depressive disorder were evaluated for long-term outcome (up to 3 years) of
      antidepressant treatment. The severity and improvement of depression were
      assessed with the Clinical Global Impression scale. The genotypes of 5-HTTLPR in
      the patients were determined using polymerase chain reaction. RESULTS: During the
      long-term treatment of antidepressants (1-3 years of treatment), clinical
      improvement of depressive symptoms was more significant for carriers of the long
      (l) allele [l/l and l/short (s) genotypes] than for those possessing the s/s
      genotype (P=0.025 at 1 year, P=0.005 at 2 years, P=0.005 at 3 years). A response
      to treatment was also significantly more frequent in carriers of the l allele
      than in those with the s/s genotype (P=0.015). CONCLUSION: These findings show
      that patients with major depressive disorder possessing the 5-HTTLPR l allele may
      exhibit a better long-term outcome when treated with antidepressants.

PMID- 15167700
TI  - Linkage disequilibrium analysis of the dopamine beta-hydroxylase gene in
      persistent attention deficit hyperactivity disorder.
AB  - Numerous family, twin and adoption studies have reported a strong genetic
      component for attention deficit hyperactivity disorder (ADHD). In addition, an
      extensive amount of literature has implicated abnormalities of the dopaminergic
      system. In view of this evidence, genes that influence dopaminergic transmission
      have become prime candidates for molecular genetic investigations of ADHD. There
      are currently three studies (Daly et al., 1999; Roman et al., 2002; Wigg et al.,
      2002) that have found an association between the dopamine beta-hydroxylase gene
      (DBH) TaqI 2 allele and childhood ADHD. As such, we tested for association of the
      DBH TaqI 2 allele in two independent samples of patients with the persistent
      variant of ADHD. These consisted of 97 nuclear families, and 112 adult cases with
      controls carefully matched according to gender, age and ethnicity. Transmission
      Disequilibrium Test analysis revealed weak over-transmission of the 2 allele (35
      transmissions versus 27 non-transmissions; chi2 = 1.03, 1 degree of freedom,
      P=0.31). The case-control sample did not support previous findings since the 2
      allele was more frequent in our control sample (137 versus 116; chi2 = 3.63, 1
      degree of freedom, P=0.057). Taken together, these results do not provide support
      for a role of the DBH TaqI marker in our persistent ADHD samples.

PMID- 15167701
TI  - A genetic test for immunosuppressant dose selection?

PMID- 15167702
TI  - The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and
      tacrolimus dose requirements and trough blood levels in stable renal transplant
      patients.
AB  - Cyclosporine and tacrolimus are immunosuppressive drugs largely used in renal
      transplantation. They are characterized by a wide inter-individual variability in
      their pharmacokinetics with a potential impact on their therapeutic efficacy or
      induced toxicity. CYP3A5 and P-glycoprotein appear as important determinants of
      the metabolism of these drugs. The objective of this study was to investigate the
      effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus
      dose requirements and trough blood concentrations in stable transplant patients.
      Stable renal transplant recipients receiving cyclosporine (n = 50) or tacrolimus
      (n = 50) were genotyped for CYP3A5*3 and *6, and MDR1 C1236T, G2677T/A and
      C3435T. Dose-adjusted trough blood levels (ng/ml per mg/kg body weight) as well
      as doses (mg/kg body weight) required to achieve target blood concentrations were
      compared among patients according to allelic status for CYP3A5 and MDR1. Dose
      adjusted trough concentrations were three-fold and 1.6-fold higher in CYP3A5*3/*3
      patients than in CYP3A5*1/*3 patients for tacrolimus and cyclosporine,
      respectively. In the case of tacrolimus, the difference was even more striking
      when considering CYP3A5*1/*1 patients showing dose-adjusted trough concentrations
      5.8-fold lower than CYP3A5*3/*3 patients. For both drugs, no association was
      found between trough blood concentrations or dose requirement and MDR1 genotype.
      Multiple regression analyses showed that CYP3A5*1/*3 polymorphism explained up to
      45% of the variability in dose requirement in relation to tacrolimus use. Given
      the importance of rapidly achieving target blood concentrations after
      transplantation, further prospective studies should consider the immediate post
      graft period and assess the influence of this specific polymorphism. Beside non
      genetic factors (e.g. steroids dosing, drugs interactions), CYP3A5
      pharmacogenetic testing performed just before transplantation could contribute to
      a better individualization of immunosuppressive therapy.

PMID- 15167703
TI  - Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3,
      MRP3) gene and relationship to its mRNA and protein expression in human liver.
AB  - AIMS: To determine the genetic variability of multidrug resistance protein 3
      (MRP3). METHODS: Genomic DNA samples from 103 Caucasians were systematically
      screened for genetic variations to find a potential relationship with hepatic
      MRP3 expression. Sequencing comprised all 31 exons, approximately 100 bp of the
      flanking intronic regions and 2 kb of the 5' UTR. RESULTS: In total, 51 mutations
      were identified. Fifteen SNPs were located in the coding exons of MRP3, six of
      which are nonsynonymous mutations. SNPs 39G>C (allele frequency: 0.5%, located in
      exon 1), 202C>T (1.6%, exon 2), 1037C>T (0.5%, exon 9), 1537C>A (0.5%, exon 12),
      3890G>A (5.2%, exon 27) and 4267G>A (0.6%, exon 29) resulted in Lys13Asn,
      His68Tyr, Ser346Phe, Gln513Lys, Arg1297His and Gly1423Arg amino acid
      substitutions, respectively. A splice site mutation (1339-1G>T) was found at the
      intron 10-exon 11 boundary. To evaluate, whether mutations in the MRP3 gene
      correlate with human hepatic MRP3 expression, we analyzed the genetic variants in
      Caucasian liver samples, whose MRP3 mRNA (n = 84) and protein (n = 50) expression
      has been determined by real time quantitative PCR and Western Blot, respectively.
      We found a significant correlation of a polymorphism in the 5' promoter region (
      211C>T) of MRP3 with mRNA expression. Individuals homozygous and heterozygous for
      the -211C>T promoter polymorphism had significantly lower MRP3 transcript levels
      compared to wild-type individuals (P < 0.05). Accordingly, electrophoretic
      mobility shift assay demonstrated that -211C>T polymorphism affected the binding
      of nuclear factors. CONCLUSIONS: Multiple genetic polymorphisms of MRP3 exist in
      Caucasians. The -211C>T promoter polymorphism appears to be associated with
      altered hepatic MRP3 mRNA expression.

PMID- 15167705
TI  - Sequence variants and haplotype analysis of serotonin transporter gene and
      association with bipolar affective disorder in Taiwan.
AB  - OBJECTIVES: Serotonin transporter (SLC6A4) is responsible for serotonin re-uptake
      into presynaptic terminals, thus fine-tuning brain serotonergic
      neurotransmission. Current studies have found associations of SLC6A4
      polymorphisms with several psychiatric traits including bipolar affective
      disorder (BPD) in various populations; however, studies with contradictory
      results were also reported. This study examined the role of SLC6A4 in etiology of
      BPD in a Taiwanese population. METHODS: Ten markers including two variable number
      tandem repeat and eight single nucleotide polymorphisms (SNPs) on the SLC6A4 gene
      were used to study the genetic association with 90 unrelated BPD, type I patients
      and 103 controls. RESULTS: Two SNPs were not informative in a Taiwanese
      population and the other eight polymorphic markers were analyzed by Fisher's
      exact test and haplotype analysis. No association was detected for any single
      SLC6A4 marker and BPD. Additional statistic analyses including other factors also
      showed lack of association between the SLC6A4 gene polymorphisms and BPD.
      Significant linkage disequilibrium was obtained among eight SLC6A4 markers and
      eight common haplotypes were constructed that can be found in 95% of the total
      subjects. The four commonest haplotypes in both patients and controls were
      identical. However, the fifth commonest haplotype differed in patients and
      controls and was significantly associated with a protection from BPD.
      CONCLUSIONS: This study suggested that a particular SLC6A4 haplotype harboring
      functional sequence variant could play a significant role in BPD etiology in
      Taiwan. However, due to its modest sample size, the conclusion is not final and
      should be confirmed in the future studies.

PMID- 15167704
TI  - Pharmacological and electrophysiological properties of the naturally occurring
      Pro391Arg variant of the human 5-HT3A receptor.
AB  - The 5-HT3A receptor, a ligand-gated ion channel, is involved in pain pathways,
      nausea and emesis, and irritable bowel syndrome, and may play a role in the
      pathogenesis of psychiatric diseases such as schizophrenia and depression.
      Recently, a naturally occurring variation (ProArg) in the second intracellular
      loop of the human (h) 5-HT3A receptor was identified in a schizophrenic patient.
      Because the substitution of proline, an alpha-imino acid, by arginine may affect
      the conformation of the whole receptor, the aim of the present study was to
      determine the pharmacological and functional properties of this variant compared
      to the wild-type receptor in stably transfected HEK293 cells. Studies of binding
      of [H]GR65630, a 5-HT3 receptor antagonist, to membranes (saturation and
      competition experiments with 5-HT3 receptor ligands) and patch-clamp studies of
      agonist-induced currents in outside-out patches were carried out. In comparison
      to the wild-type, the variant receptor exhibited no changes in the receptor
      density and the affinities for nine representative ligands (five agonists and
      four antagonists). The potencies and efficacies of three 5-HT3 receptor agonists
      in inducing currents through the ion channel and the potencies of two 5-HT3
      receptor antagonists in blocking 5-HT-evoked currents did not differ between wild
      type and variant receptors. In addition, there were no differences in the
      desensitization kinetics of both receptor isoforms. In conclusion, the ArgPro
      variation of the h5-HT3A receptor does not change ligand binding to the h5-HT3A
      receptor, nor does it modify current through the receptor channel.

PMID- 15167706
TI  - Adverse drug reactions to azathioprine therapy are associated with polymorphism
      in the gene encoding inosine triphosphate pyrophosphatase (ITPase).
AB  - Adverse drug reactions to azathioprine (AZA), the pro-drug of 6-mercaptopurine (6
      MP), occur in 15% to 28% of patients and the majority are not explained by
      thiopurine methyltransferase (TPMT) deficiency. Inosine triphosphate
      pyrophosphatase (ITPase) deficiency results in the benign accumulation of the
      inosine nucleotide ITP. 6-MP is activated through a 6-thio-IMP intermediate and,
      in ITPase deficient patients, potentially toxic 6-thio-ITP is predicted to
      accumulate. The association between polymorphism in the ITPA gene and adverse
      drug reactions to AZA therapy was studied in patients treated for inflammatory
      bowel disease. Sixty-two patients with inflammatory bowel disease suffering
      adverse drug reactions to AZA therapy were genotyped for ITPA 94C>A and IVS2 +
      21A>C polymorphisms, and TPMT*3A, *3C, *2 polymorphisms. Genotype frequencies
      were compared to a consecutive series of 68 controls treated with AZA for a
      minimum of 3 months without adverse effect. The ITPA 94C>A deficiency-associated
      allele was significantly associated with adverse drug reactions [odds ratio (OR)
      4.2, 95% confidence interval (CI) 1.6-11.5, P = 0.0034]. Significant associations
      were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, P = 0.0308), rash (OR
      10.3, 95% CI 4.7-62.9, P = 0.0213) and pancreatitis (OR 6.2,CI 1.1-32.6, P =
      0.0485). Overall, heterozygous TPMT genotypes did not predict adverse drug
      reactions but were significantly associated with a subgroup of patients
      experiencing nausea and vomiting as the predominant adverse reaction to AZA
      therapy (OR 5.5, 95% CI 1.4-21.3, P = 0.0206). Polymorphism in the ITPA gene
      predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6
      thioguanine, should be considered for AZA-intolerant patients with ITPase
      deficiency.

PMID- 15167707
TI  - Differential transcriptional expresion of the polymorphic myxovirus resistance
      protein A in response to interferon-alpha treatment.
AB  - Levels of myxovirus resistance protein A (MxA) mRNA were studied for a single
      nucleotide polymorphism in the promoter region at nucleotide position -88 of the
      gene to identify individual-specific responses to interferon (IFN)-alpha2 that
      might predict responsiveness to IFN-alpha therapy. We quantified MxA expression
      by reverse transcription and real-time polymerase chain reaction in peripheral
      blood mononuclear cells (PBMC) in vitro, induced by IFN-alpha2, from 22 healthy
      donors, in relation with G/T polymorphism located in the promoter of the MxA. MxA
      mRNA was significantly upregulated in all subjects (mean of 53-fold) in response
      to IFN-alpha2 in vitro (P < 0.01). Comparison of the inducibility of MxA mRNA
      expression in relation with G/T polymorphism showed a 4.26-fold higher induction
      of MxA mRNA levels in PBMC from carriers of the mutant allele (GT or TT) than
      homozygotes with the wild-type allele (GG) (P < 0.001). We propose that
      expression of the IFN-inducible MxA is affected by a single nucleotide
      polymorphism in the MxA promoter which can identify an individual response to IFN
      alpha2.

PMID- 15167708
TI  - Study of the involvement of research ethics committees in the constitution and
      use of biobanks in France.
AB  - Concerns are emerging about the protection of individuals who take part in
      genetic research involving biobanks. We used several items of a questionnaire
      sent to 48 French research ethics committees (RECs) to investigate the means by
      which they evaluate the constitution and use of biobanks, and the elements on
      which conclusions were based. Most RECs felt they should evaluate the
      constitution of biobanks in protocols, but not all did so in practice.
      Harmonization of the competence of RECs for evaluating biobanks is required,
      particularly concerning information, consent, the duration of sample conservation
      and the communication of research results. Our results, together with those of
      others, demonstrate the need to develop rules and guidelines based on common
      ethical approaches, particularly in the European environment.

PMID- 15167709
TI  - A proposed nomenclature system for the cytosolic sulfotransferase (SULT)
      superfamily.
AB  - A nomenclature system for the cytosolic sulfotransferase (SULT) superfamily has
      been developed. The nomenclature guidelines were applied to 65 SULT cDNAs and 18
      SULT genes that were characterized from eukaryotic organisms. SULT cDNA and gene
      sequences were identified by querying the GenBank databases and from published
      reports of their identification and characterization. These sequences were
      evaluated and named on the basis of encoded amino acid sequence identity and, in
      a few cases, a necessity to maintain historical naming convention. Family members
      share at least 45% amino acid sequence identity whereas subfamily members are at
      least 60% identical. cDNAs which encode amino acid sequences of at least 97%
      identity to each other were assigned identical isoform names. We also attempted
      to categorize orthologous enzymes between various species, where these have been
      identified, and the nomenclature includes a species descriptor. We present
      recommendations for the naming of allelic variants of SULT genes and their
      derived allozymes arising from single nucleotide polymorphisms and other genetic
      variation. The superfamily currently comprises 47 mammalian SULT isoforms, one
      insect isoform and eight plant enzymes, and collectively these sequences
      represent nine separate SULT families and 14 subfamilies. It is hoped that this
      nomenclature system will be widely adopted and that, as novel SULTs are
      identified and characterized, investigators will name their discoveries according
      to these guidelines.

PMID- 15167710
TI  - Forgoing life support across borders: who decides and why?

PMID- 15167712
TI  - Implications of sleep deprivation for children in the pediatric intensive care
      unit.

PMID- 15167711
TI  - Toward an ethics of communication among countries.

PMID- 15167713
TI  - He/she has fallen, but we can't come up with an approach to evaluate him/her: the
      role of computed tomography scans and physical findings in minor head injury.

PMID- 15167714
TI  - Bouncing back from inhaled nitric oxide.

PMID- 15167715
TI  - Base deficit is a poor indicator of tissue acidosis.

PMID- 15167717
TI  - Cerebrovascular dynamics in head-injured children.

PMID- 15167716
TI  - Pharmacologic therapy for postoperative bleeding in children after cardiac
      surgery: when will the bleeding stop?

PMID- 15167718
TI  - Jading: requiring critical care.

PMID- 15167723
TI  - Botulinum toxin type a for dysthyroid upper eyelid retraction.
AB  - PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A for
      treatment of eyelid retraction resulting from thyroid eye disease (TED) during
      the inflammatory phase of the condition. METHODS: In this prospective,
      nonrandomized case series, 18 patients with inflammatory eyelid retraction caused
      by active TED received botulinum toxin type A injection (10, 5, or 2.5 U) for
      treatment of upper eyelid retraction. Botulinum toxin type A (Allergan, Irvine,
      CA, U.S.A.) was injected transconjunctivally just above the superior tarsal
      border in the elevator complex of the upper eyelid. RESULTS: Seventeen of 18
      patients (94%) demonstrated a reduced marginal reflex distance (MRD1) after
      botulinum toxin injection. The average change in MRD1 of the treated eyelid after
      injection was -2.35 mm (range, 0 to -8.0 mm). Of the 27 eyelids injected, 33% had
      a 0- to 1-mm drop in eyelid height, 30% had a 1.5- to 2-mm decrease, 22% had a
      2.5- to 3-mm decrease, and 15% had a greater than 3-mm decrease in eyelid height.
      None of the treated eyelids were noted to increase in height. One patient showed
      no alteration inafter treatment. One patient had clinically MRD1 significant
      ptosis and one patient reported worsening of preexisting diplopia after
      injection. Three patients undergoing unilateral injection had relative
      contralateral eyelid elevation. All untoward effects resolved spontaneously
      without sequelae. CONCLUSIONS: : Botulinum toxin type A may be used in the
      inflammatory stage of thyroid eye disease to improve upper eyelid retraction.
      Individual response to treatment is variable, but this modality should be
      considered as a temporizing measure until stability for surgery is reached.

PMID- 15167724
TI  - Increased patient comfort utilizing botulinum toxin type a reconstituted with
      preserved versus nonpreserved saline.
AB  - PURPOSE: To demonstrate that injection of botulinum toxin type A is less painful
      when mixed with preserved saline compared with the suggested preservative-free
      saline reconstitution. METHODS: Two different injections were compared on 20
      patients who had prior botulinum toxin type A treatments. Each side was injected
      with toxin reconstituted with either preserved or nonpreserved (0.9%) saline. The
      investigators and patients were blinded, and outcome was assessed with a verbal
      scale. Clinical outcome was subjectively and informally assessed by patient
      questioning and physician observation. RESULTS: Injection of botulinum toxin type
      A was noted to be less painful with the use of the preserved compared with the
      nonpreserved preparation (P<0.0001). The preserved reconstitution appeared to
      have no effect on clinical outcome. CONCLUSIONS: Injection of botulinum toxin
      reconstituted with preserved saline is less painful than nonpreserved saline
      preparations.

PMID- 15167726
TI  - Causes of undercorrection of medial palpebral fissures in blepharoptosis surgery.
AB  - PURPOSE: To ascertain the cause of undercorrection of the medial palpebral
      fissure in blepharoptosis surgery. METHODS: Twelve upper eyelids of 6 Asian
      cadavers, 4 male and 2 female (average age at death, 77.5 years), were studied.
      After exposing the levator muscle by removing bone of the superior orbital rim,
      the levator muscle and medial and lateral horns of aponeurosis were observed.
      RESULTS: The levator muscle was located in the anterolateral direction.
      Bifurcation angles of the medial horn were steeper than those of the lateral
      horn, but the lateral horn was wider than the medial horn (Student's t test; P <
      0.0001). The inferior edge of the superior expansion of the aponeurosis
      extensively covered the lateral horn but only slightly covered the medial horn.
      Accordingly, most of the medial horn was constituted by only the thin structure
      of the middle and inferior expansion of the aponeurosis. CONCLUSIONS: Because the
      medial horn is structurally weaker and less dynamic than the lateral horn, the
      lateral side of the aponeurosis is pulled more strongly than the medial, often
      resulting in medial undercorrection in blepharoptosis surgery. To prevent this,
      the medial part should be fixed more widely than the lateral.

PMID- 15167728
TI  - Microscopic anatomy of the lower eyelid in asians.
AB  - PURPOSE: To study the microscopic anatomic relation of the capsulopalpebral
      fascia, orbital septum, and tarsus of the lower eyelid in Asians. The anatomic
      differences between the Asian and non-Asian upper eyelid have been well described
      by various authors, but the differences of the lower eyelid have not been well
      characterized microscopically. The microscopic anatomy of the lower eyelid in non
      Asians was well studied, but in Asians, despite the presence of gross
      differences, there were very limited studies on the microscopic anatomy. A
      thorough knowledge of the Asian lower eyelid anatomy is essential for surgical
      exploration of the eyelid. It may also explain the higher prevalence of eyelid
      disorders such as epiblepharon and entropion in Asians. METHODS: Ten normal Asian
      lower eyelids from 10 formalin-fixed cadavers (mean age, 67.5 years) were
      harvested and studied with light microscopy after staining with Masson trichrome.
      RESULTS: There was no fusion of the orbital septum and the capsulopalpebral
      fascia at the lower border of the tarsal plate in 7 specimens and a very limited
      fusion of these tissues in 3 specimens. The average distance from the inferior
      tarsal border to the first observable smooth muscle nuclei of the inferior
      retractors was 1.44 mm. The average tarsal plate thickness was 1.36 mm and the
      average tarsal plate height was 4.12 mm. CONCLUSIONS: The Asian lower eyelid
      anatomy differs from its non-Asian counterpart. There was no consistent fusion
      between the capsulopalpebral fascia and the orbital septum inferior to the
      inferior tarsal border. No extension of the capsulopalpebral fascia to the skin
      was observed. The average distance between the inferior retractors and the
      inferior tarsal plate was 1.44 mm in the normal Asian lower eyelid.

PMID- 15167725
TI  - Recent trends in upper eyelid blepharoplasties in medicare patients in the United
      States from 1995 to 1999.
AB  - PURPOSE: To present data regarding the rate of upper eyelid blepharoplasty in the
      Medicare population at both the national and the regional levels from 1995 to
      1999 and to analyze these data for any correlation with reimbursement, surgical
      criteria differences, or the number of ophthalmologists per capita. METHODS: This
      was a retrospective cohort study. The subjects consisted of a 5% random sample of
      the Medicare population who had blepharoplasty from 1995 to 1999. Number, rate,
      and reimbursements of blepharoplasty of the 10 Health Care Financing
      Administration (HCFA) regions were compared for the 5-year period. Number of
      ophthalmologists per capita and differences in the regional criteria for Medicare
      approved upper eyelid blepharoplasty were compared among the 10 HCFA regions.
      RESULTS: Across the nation, there was a 13% annual increase in the rate of
      blepharoplasty from 1995 to 1999 in the Medicare-population after adjusting for
      age, race, sex, and HCFA regions. During the same period, the average
      reimbursement per surgery decreased by $26.50 annually. There was a statistically
      significant inverse correlation between reimbursement and rate of blepharoplasty
      at the national level (r= - 0.74, P< 0.001). On the regional level, this relation
      was less profound (r= -0.29, P= 0.039). There was no correlation between the rate
      of blepharoplasty and the number of ophthalmologists per capita or the
      differences in surgical criteria. CONCLUSIONS: The inverse relation between rate
      of Medicare-approved blepharoplasty and reimbursement between 1995 and 1999 was
      evident at both the national and regional levels. No relation between regional
      differences in the rates of blepharoplasty and regional differences in surgical
      criteria or the number of ophthalmologists per capita were identified. Though our
      study suggests no causal link between annual rate of blepharoplasty and Medicare
      reimbursement, such inverse correlation is interesting and may have been affected
      by other factors such as changing clinical indications for this procedure.

PMID- 15167727
TI  - Gold weight implantation: a better way?
AB  - PURPOSE: To introduce an alternative surgical technique for gold weight
      implantation for the treatment of lagophthalmos. We suggest that unwrapped
      intraorbital gold weight implantation provides adequate function, better cosmetic
      appearance, and lower morbidity than conventional implantation with wrapped or
      unwrapped pretarsal gold weights. METHODS: The charts of a single surgeon were
      reviewed (1994 to 2003). All patients who underwent intraorbital gold weight
      implantation were included in the study. The technique was noted to be consistent
      with intraorbital fixation of a custom 2.2-gm gold weight (MedDev Corporation,
      Sunnyvale, California). Implants were not wrapped. Efficacy was defined as
      elimination of exposure keratopathy with preservation of the visual axis.
      Morbidity was defined as extrusion of the weight, shift of positioning requiring
      intervention, inflammation/infection of the eyelid, or poor cosmetic appearance.
      RESULTS: Of 59 patient charts reviewed, 2 patients had morbidity as defined by
      our study: One had shifting of the gold weight, necessitating repositioning of
      the weight; the other had extrusion of the gold weight, requiring its removal.
      The remaining patients had no complaints or cosmetic concerns. Follow-up
      examinations found no incidence of exposure keratopathy. CONCLUSIONS: We found
      intraorbital gold weight implantation, without the use of a wrap, to be simple
      and effective, with adequate function, an acceptably low postoperative morbidity
      rate, and an excellent cosmetic outcome.

PMID- 15167729
TI  - Eyelid involvement in paracoccidioidomycosis.
AB  - PURPOSE: To describe a series of patients with eyelid lesions caused by
      paracoccidioidomycosis and to estimate the prevalence of eyelid involvement in
      this disease METHODS: The medical records of 439 patients with
      paracoccidioidomycosis admitted to our hospital from 1992 to 2002 were reviewed.
      Age, sex, and clinical forms of the disease were recorded. All patients with
      eyelid involvement had a skin biopsy positive for paracoccidioidomycosis and were
      examined by an ophthalmologist with oculoplastic training. RESULTS: Of 439
      patients with acute, subacute, or chronic paracoccidioidomycosis, 11 (2.5%) had
      eyelid involvement. Active lesions ranged from erythematous patches of madarosis
      to frank destructive ulcers indistinguishable from malignancies. Healed lesions
      were characterized by a high degree of fibrosis. Cicatricial changes induced
      eyelid malpositions (entropion or ectropion) and fusion of eyelid tissues to the
      globe. Madarosis was a constant finding in the inactive lesions. CONCLUSIONS: The
      prevalence of eyelid involvement in paracoccidioidomycosis is low. Isolated
      active lesions are usually diagnosed as malignant tumors. Cicatricial changes are
      characterized by a high degree of fibrosis. If not treated, the mycosis can
      destroy the eyelid.

PMID- 15167730
TI  - Manifestations of fungal cellulitis of the orbit in children with neutropenia and
      fever.
AB  - PURPOSE: To delineate clinical manifestations of fungal orbital cellulitis in
      immunocompromized patients. METHODS: The charts of 7 pediatric patients with
      fungal orbital cellulitis treated at a tertiary children's cancer hospital were
      reviewed retrospectively for histologically confirmed fungal sinusitis with
      associated orbital cellulitis. Patients underwent CT and/or MRI of the orbits,
      sinuses, and brain; surgery; and therapy with antifungal medications. Main
      outcome measures were presenting signs and patient survival. RESULTS: Twenty-four
      patients with fungal sinusitis were identified, 7 of whom (4 months to 15 years
      of age) had documented orbital fungal cellulitis. All 7 patients presented with
      neutropenia and fever. Presenting symptoms included edema of the upper eyelid
      (n=4), headache (n=1), and facial pain (n=1). One patient was asymptomatic.
      Although antifungal therapy was initiated within 24 hours of presentation,
      disease progressed, and 5 patients eventually died of their infections.
      CONCLUSIONS: Because fungal orbital cellulitis can be fatal even if detected
      early in patients who are immunocompromised, ophthalmologists and
      otolaryngologists should be alert to the disease's subtle clinical
      manifestations.

PMID- 15167731
TI  - Prevalence of asymmetric exophthalmos in Graves orbitopathy.
AB  - PURPOSE: To report the prevalence and the degree of significant asymmetric
      orbital involvement secondary to thyroid-related (Graves) orbitopathy in a large
      patient population. METHODS: The prevalence of exophthalmometric differences of >
      or =2 mm was determined in 391 consecutive patients diagnosed with Graves
      orbitopathy from the Jules Stein Eye Institute Division of Ophthalmic Plastic and
      Reconstructive Surgery patient registry. RESULTS: Thirty-six of 391 patients (9%)
      in this cohort had asymmetric proptosis with a difference of > or =2 mm, based on
      single-observer Hertel measurements before orbital decompression surgery. This
      finding was similar among men (11/95, 12%) and women (25/296, 8%) but was not
      statistically significant (P= 0.358; 95% CI, 0.6% to 7.8%). Also, we found no
      racial variations in the incidence of unilateral disease. CONCLUSIONS:
      Clinically, unilateral or asymmetric Graves orbitopathy is common and can lead to
      misdiagnosis or to unnecessary testing. Thyroid-related orbitopathy must be
      considered in the differential diagnosis for any case of asymmetric exophthalmos.

PMID- 15167732
TI  - Effect of preemptive retrobulbar analgesia on perioperative hemodynamics and
      postoperative pain after enucleation.
AB  - PURPOSE: To determine the preemptive pain and hemodynamic effects of
      preincisional retrobulbar analgesia in enucleation. METHODS: This double-blinded,
      placebo-controlled study enrolled 69 patients scheduled for enucleation. Patients
      were stratified into two groups: those who used daily analgesics before surgery
      and those who did not. Each group was randomly assigned to receive a
      preincisional retrobulbar injection containing either a mixture of bupivacaine,
      lidocaine, epinephrine, and hyaluronidase; or saline placebo. All patients
      received postoperative retrobulbar injection containing the analgesic mixture.
      The outcome measures were intraoperative and postoperative blood pressure, heart
      rate, postoperative pain, and pain medication consumption. RESULTS: Groups that
      received preincisional analgesia had a significantly lower mean intraoperative
      blood pressure (109/59 versus 127/69 mm Hg; P< 0.05). Visual analog scale pain
      assessment (VAS) was lower in both treatment groups upon recovery room entry
      (VAS, 0.3 versus 15.8, P=0.08) and after 30 minutes in the nonanalgesic use group
      (VAS, 5.6 versus 19.4, P=0.11). Among nonchronic analgesic users, fewer patients
      in the treatment group had pain requiring analgesic rescue in the recovery room
      (5% versus 25%, P=0.08). Postoperative pain medicine consumption in the first 24
      hours did not differ significantly among the groups. CONCLUSIONS: Preemptive
      retrobulbar analgesia was associated with improved intraoperative hemodynamics
      during enucleation and a trend toward reduced pain on entry in the recovery room
      and fewer pain rescues in the early postoperative period. A trend toward reduced
      pain severity in the early postoperative period was observed in those patients
      without daily preoperative analgesic use.

PMID- 15167733
TI  - Retained intraorbital metallic foreign bodies.
AB  - PURPOSE: To document the biological tolerance of retained metallic orbital
      foreign bodies managed with conservative treatment. METHODS: A retrospective
      chart review of 43 patients treated between 1987 and 1993 with retained
      intraorbital metallic foreign bodies was performed. Age, sex, injury, imaging
      studies obtained, location of the foreign body, initial and final visual acuity,
      length of follow-up, treatment, and related adverse reactions and/or
      complications were recorded. RESULTS: Fifty cases involving 34 male and 9 female
      patients ranging in age from 2 through 63 years (median, 25 years) were included.
      Seventeen cases were the result of gunshot wounds, 17 were from BB gun injuries,
      and 16 cases were from shotgun injuries. Forty-two patients had CT scans to
      assess the injury and one patient had plain radiographs. In 37 cases, the
      metallic foreign bodies were located posterior to the globe. There were 19 ocular
      penetrating injuries, 11 ocular contusion injuries (sclopetaria, commotio
      retinae, vitreous hemorrhages), and 20 injuries with no ocular involvement.
      Initial visual acuity ranged from 20/20 to no light perception, as did final
      visual acuity. The metallic foreign bodies were retained from 6 months to 68
      years (median, 2 years). There were 19 ocular penetrating injuries, including 12
      enucleations and 7 primary repairs. When contusion injuries were sustained,
      treatment consisted of vitrectomy for the removal of persistent hemorrhages (3
      cases), exploration of the globe (1 case), and nonsurgical treatment (7 cases).
      Among the 20 cases with no ocular involvement, only 2 patients had secondary
      complications that required surgical intervention: One had mechanical strabismus,
      the other a sterile abscess. Visual acuity remained stable or improved in all
      cases. There were no late complications from the retained foreign bodies in 36
      (95%) of 38 cases when the eye remained intact. CONCLUSIONS: Retained
      intraorbital metallic foreign bodies are well-tolerated and typically have
      minimal adverse visual prognosis. They should be managed conservatively in the
      absence of specific indications for removal.

PMID- 15167734
TI  - Surgical technique: use of quilting sutures in ophthalmic plastic surgery.

PMID- 15167735
TI  - Modified technique for tube fixation in conjunctivodacryocystorhinostomy.
AB  - The standard glass tube used with a conjunctivodacryocystorhinostomy is subject
      to spontaneous displacement or extrusion, especially in the early postoperative
      period. To anchor the tube in the surrounding tissues, a suture is commonly tied
      around the collar of the Pyrex tube and externalized to the skin of the medial
      canthal area where it is fixed. The loop can become loose around the tube, and
      displacement or extrusion can occur. We describe an alternative method to better
      secure the tube in place during the early postoperative period and until the time
      when the tissues around the tube contract.

PMID- 15167736
TI  - Delayed enophthalmos following a minimally displaced orbital floor fracture.
AB  - We describe a case of an orbital floor fracture resulting in obstruction of the
      maxillary sinus ostium by herniated orbital contents. Our patient had delayed
      enophthalmos in a manner similar to silent sinus syndrome or imploding antrum
      syndrome. Obstruction of the maxillary sinus ostium by orbital contents carries
      the potential for delayed-onset enophthalmos and therefore suggests an additional
      indication for orbital floor fracture repair.

PMID- 15167737
TI  - Pediatric canaliculitis and stone formation.
AB  - A 5-year-old girl with a remote history of idiopathic thrombocytopenic purpura
      presented with a history of partial nasolacrimal duct obstruction unresolved with
      standard treatments of probing, irrigation, and lacrimal system intubation.
      Surgical exploration revealed canaliculitis with dacryolith formation within the
      inferior canalicular system. After punctoplasty and removal of the dacryoliths,
      the patient had full resolution of symptoms. Although the diagnosis is uncommon
      in this age group, it should be included in the differential diagnosis of chronic
      or recurrent pediatric nasolacrimal obstruction.

PMID- 15167738
TI  - Primary congenital upper eyelid retraction in infants and children.
AB  - Four infants with unilateral or bilateral eyelid retraction were examined. A full
      clinical evaluation revealed no ocular or systemic pathology. In all cases,
      clinical examination, thyroid function tests, and neuroimaging of the brain and
      orbits revealed no underlying disease process. The eyelid retraction did not
      change over the follow-up period of 2 to 6 years. Unilateral or bilateral eyelid
      retraction in infants and children may be an isolated clinical entity without an
      associated underlying disease.

PMID- 15167739
TI  - Bilateral leukemic orbital infiltration presenting as proptosis and narrow-angle
      glaucoma.
AB  - A 71-year-old man with acute myeloid leukemia presented with bilateral uveal and
      orbital leukemic infiltration presenting as tense bilateral proptosis, orbital
      inflammation, and acute-angle closure glaucoma. B-scan ultrasonography revealed
      uveoscleral thickening and anterior rotation of the ciliary body. Orbital CT and
      MRI showed bilateral proptosis with streaking of intraconal fat. Temporary
      pressure lowering occurred after lateral canthotomy and inferior cantholysis.
      Definitive treatment included systemic chemotherapy and steroids. Over a 2-week
      period, vision improved and proptosis resolved, and the intraocular pressure
      returned to normal. The patient died of cerebral complications of his illness
      after 6 weeks. This is the first reported case of orbital and ocular leukemic
      infiltration presenting simultaneously as tense proptosis and narrow-angle
      glaucoma.

PMID- 15167740
TI  - Missed diagnosis of an intraorbital foreign body of surfboard origin.
AB  - Surfing is a highly popular recreational sport in Australia and other parts of
      the world. A significant percentage of total acute injuries in surfboarding
      involve the head and neck, but major orbital or ocular trauma is infrequent.
      Ophthalmic injuries are typically due to blunt trauma from collision with the
      surfboard. We describe a mechanism of surfboard injury not previously described
      in the published literature, which involved penetration of orbital tissues by
      blade-like fragments of fiberglass when the surfboard outer shell broke up on
      impact with the surfer. The fiberglass left a trail of fibers and resin particles
      as it traveled through the eyelid and orbital tissues, requiring painstaking
      removal and debridement to minimize the long-term effects of inflammatory
      reactions and scarring in the orbital tissues.

PMID- 15167741
TI  - Involvement of the bony orbit in infantile myofibromatosis.
AB  - Infantile myofibromatosis is a rare disorder of infancy that can provoke
      osteolytic lesions. A 15-day-old infant presented with three round, firm lesions
      located on the forehead, shoulder, and back. Excisional biopsy of the forehead
      lesion revealed that the tumor was composed of spindle cells resembling normal
      smooth muscle arranged in short fascicles. Immunohistochemical staining was
      positive for vimentin and actin. Five months later, the child presented with
      three new lesions, including one in the superolateral aspect of the left orbit.
      It is important to recognize the multicentric form of infantile myofibromatosis
      because, despite its aggressive clinical presentation, the disease is benign and
      usually does not require extensive surgery or chemotherapy.

PMID- 15167742
TI  - Vasculitis of the lacrimal sac wall in Wegener granulomatosis.
AB  - A 35-year-old woman with a 4-year history of generalized Wegener granulomatosis
      (WG) had clinically controlled disease. She was evaluated for a 6-month history
      of right lacrimal sac mass. On examination, a right chronic dacryocystitis and
      mucocele were observed. A right external dacryocystorhinostomy was performed. The
      surgical biopsy specimen from the lacrimal sac showed leukocytoclastic vasculitis
      with more aggressive damage to the small vessels in the deeper mucosa and focal
      microhemorrhages. The patient was free of symptoms 1 year after surgery. We
      believe this is the first report of generalized WG presenting features of an
      active vasculitis of the lacrimal sac wall on surgical biopsy specimen. We
      conclude that the lacrimal drainage system can be affected directly by focal WG
      vasculitis, suggesting that nasolacrimal duct obstruction is not always due to
      contiguous paranasal disease.

PMID- 15167743
TI  - Localized inferior orbital fibrosis associated with porcine dermal collagen
      xenograft orbital floor implant.
AB  - We describe the clinical features, treatment, and histologic changes of a case of
      severe localized orbital inflammation associated with the use of porcine dermal
      collagen xenograft (Permacol) as an orbital floor implant in a 14-year-old boy.
      After uneventful blowout fracture repair with normal forced duction testing after
      insertion of a Permacol implant, progressive elevation and depression deficit
      developed in the postoperative period. There was no improvement after removal of
      the Permacol implant. Exploratory surgery revealed gross fibrosis of the inferior
      rectus muscle accounting for the abnormal ocular motility. Biopsy of the inferior
      rectus muscle showed chronic granulomatous inflammation suggestive of foreign
      body reaction. Although porcine dermal collagen xenograft has been suggested as
      an implant for orbital floor repair because of its reported high strength, ease
      of handling, and high biocompatibility, we believe that further studies are
      necessary before it can be recommended for this use.

PMID- 15167744
TI  - Memorable medical mentors: V. Nicholson J. Eastman.

PMID- 15167745
TI  - Pregnancy outcome and plasma volume expansion: a continuing concern.

PMID- 15167766
TI  - Hip fracture prevention in postmenopausal women.
AB  - Hip fracture is a devastating outcome associated with postmenopausal
      osteoporosis. This fracture causes considerable pain, disability, diminished
      quality of life, and mortality. Although bone loss is an important factor
      associated with hip fracture, there are other demographic and clinical factors
      such as those that increase the risk of falling (e.g., unsteady gait,
      medications) that contribute to the likelihood of experiencing a hip fracture.
      Nonpharmacological interventions to reduce hip fracture risk include regular
      weight-bearing exercise, fall intervention programs, and external hip protectors.
      Patients should receive calcium and/or vitamin D supplementation as necessary.
      Among available pharmacologic options, the bisphosphonates, risedronate (Actonel)
      and alendronate (Fosamax), have reduced the risk of hip fracture in
      postmenopausal women with osteoporosis. Raloxifene (Evista), salmon calcitonin
      nasal spray (Miacalcin), and teriparatide (Forteo) have not demonstrated hip
      fracture risk reduction in controlled clinical trials. Hormone therapy (HT)
      reduced hip fracture risk in a recent large placebo-controlled trial; however,
      the risk/benefit profile of HT has resulted in recommendations to consider
      alternatives for the management of osteoporosis. Postmenopausal women with
      osteoporosis should receive adequate calcium/vitamin D supplementation, be
      encouraged to exercise, and institute risk factor interventions. Treatment with a
      bisphosphonate should be considered for those who are also at increased risk for
      hip fracture. TARGET AUDIENCE: Obstetricians & Gynecologyists, Family Physicians
      LEARNING OBJECTIVES: After completion of this article the reader should be able
      to list the demographic risk factors for osteoporosis and related fractures, to
      outline the cost and consequences of hip fractures, and to summarize the various
      pharmacologic and non-pharmacologic interventions used to reduce the risk of hip
      fracture.

PMID- 15167767
TI  - Oral hypoglycemic agents in pregnancy.
AB  - Pregnancies in diabetic women are associated with increased risk of spontaneous
      abortion, congenital malformations, preeclampsia, preterm labor, macrosomia,
      shoulder dystocia, and cesarean section. Advances in antepartum cares and strict
      adherence to dietary and insulin regimens have been shown to significantly reduce
      the rate of maternal morbidity as well as perinatal morbidity and mortality.
      Historically, reports of potential fetal teratogenicity and hypoglycemic effects
      on the fetus contraindicated the use of oral hypoglycemic agents in pregnancies
      complicated with either type II diabetes mellitus (DM) or gestational diabetes
      mellitus (GDM). Recently, physicians increasingly prescribe newer generations of
      oral hypoglycemic agents to treat GDM and type II DM to pregnant patients. This
      review addresses the safety, current recommendations, and controversies
      surrounding use of the available oral hypoglycemic agents during pregnancy.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to
      describe the mechanisms of actions of the various oral hypoglycemic agents, to
      list the known side effects of these agents, and to summarize the data on the use
      of these agents during pregnancy.

PMID- 15167772
TI  - Factors affecting the temporal stability of semipermanent bilayer coatings in
      capillary electrophoresis prepared using double-chained surfactants.
AB  - Surfactants such as didodecyldimethylammonium bromide (DDAB) adsorb onto fused
      silica capillaries to form semipermanent bilayer coatings. However, such coatings
      must be regenerated between runs to maintain efficiency and reproducibility. In
      this paper, chemical and physical factors affecting the stability of DDAB
      coatings are investigated. Chemical factors such as ionic strength and the nature
      of the buffer anion (e.g., from acetate to phosphate), which decrease the
      critical micelle concentration of DDAB, improve the coating stability. Increasing
      buffer pH also increases the coating stability. Finally, reducing the capillary
      diameter and reducing the volume of buffer flushed through the capillary enhance
      the coating stability. Using 50 mM acetate, pH 5.0, in a 25-microm-i.d.
      capillary, cationic proteins were separated with efficiencies of 1.05 million
      plates/m and a run-to-run migration time reproducibility of 0.6-0.8% RSD for 10
      successive runs without regeneration of the DDAB coating between runs.

PMID- 15167768
TI  - Prediction of preeclampsia: can it be achieved?
AB  - In this review, the various biochemical tests that have been proposed for the
      prediction of preeclampsia are described and evaluated. Placenta hormone markers
      do not predict future disease. They denounce the early placental changes that are
      part of the evolving disease and only predict the imminent of preeclamptic
      syndrome. This explains why tests are better predictors when preeclampsia
      supervenes shortly, and why screening in the first trimester is unlikely to work
      as well as in the second trimester. The use of multiple markers in the screening
      should reflect different aspects of the disease process and could increase the
      specificity and sensitivity of the screening and work on different etiologic
      factors. The possible use of second-trimester biochemical screening to predict
      the risk of preeclampsia remains to be investigated in the high-risk population.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to list
      the various theories on the etiology of preeclampsia, to relate the various risk
      factors for the development of preeclampsia, and to describe the various
      screening tests for preeclampsia.

PMID- 15167773
TI  - On-demand mixing droplet spotter for preparing picoliter droplets on surfaces.
AB  - An on-demand mixing droplet spotter for generating and mixing picoliter droplets
      has been developed for ultrasmall reaction vessels. The droplets were generated
      by applying a approximately 500-V, approximately 2-ms pulsed voltage to the tips
      of capillary tubes (o.d. approximately 20 microm; i.d. approximately 12 microm)
      filled with solution. The mixing process was achieved using electrostatic force.
      The initial droplet was formed by applying the pulsed voltage between one
      capillary and the substrate, and the second jet of the other solution was
      generated from the other capillary and collided with the initial droplet
      automatically because the electric field lines concentrated on the initial
      droplet. Using this mixing process, a microarray having a concentration gradient
      was obtained by spotting approximately 6-pL droplets on a surface with a density
      of one spot per 75 x 75 microm(2).

PMID- 15167775
TI  - High-velocity transport of nanoparticles through 1-D nanochannels at very large
      particle to channel diameter ratios.
AB  - We explore the possibility of generating high-velocity flows of nanoparticles
      through flat-rectangular nanochannels, which are only 50% deeper than the
      diameter of the particles. Using the shear-driven flow principle, 200-nm
      particles can, for example, be transported through a 300-nm-deep channel at
      velocities up to 35 mm/s (upper limit of our current setup). Working under high
      pH conditions, the velocity of the carboxylated nanoparticles still respects the
      small-molecule velocity law, despite the high degree of confinement to which the
      particles are subjected. The high degree of confinement is also found to lead to
      a reduced band broadening. When injecting sharply delimited particle plugs, the
      plate heights observed for the flow of 0.2-microm particles through a 0.3-microm
      channel (with plate heights of the order of 1-2 microm) are, for example,
      approximately 1 order of magnitude smaller than for the flow of 1.0-microm
      particles through a 1.4-microm channel. It is also found that the band broadening
      is, within its statistical variation, independent of the fluid velocity over a
      large range of particle velocities (5-35 mm/s). The flow method distinguishes
      itself from pressure-driven field-flow fractionation and hydrodynamic
      chromatography in that the mean particle velocity is independent of the particle
      size over the entire range of possible particle to channel diameter ratios.

PMID- 15167774
TI  - Chemiluminescent image detection of haptoglobin phenotyping after polyacrylamide
      gel electrophoresis.
AB  - The development of an enhanced chemiluminescence detection method for the rapid
      detection of haptoglobin phenotyping after polyacrylamide gel electrophoresis is
      described in this paper. The enhanced chemiluminescence detection is based upon
      chemiluminescent reaction between luminol and hydrogen peroxide. Increased
      sensitivity and dynamic range are achieved by employing ammonium persulfate to
      enhance the chemiluminescence signal. Detection of haptoglobin phenotypes in
      human blood serum was easily achieved even without the addition of hemoglobin.
      Different polyacrylamide gel electrophoresis results were found between pure
      serum and hemoglobin-supplemented serum. Applying the suggested enhanced
      chemiluminescence detection, the original combining forms of haptoglobin and
      hemoglobin can be detected. The linear range of haptoglobin is 0.1-13.3
      microg/mL, with a detection limit of 1.21 ng (sample loading volume 15 microL).
      Other proteins, such as catalase and ferritin, can also be detected using
      enhanced chemiluminescence detection. All detections after polyacrylamide gel
      electrophoresis were completed within 15 min. The proposed detection is very
      fast, compared to traditional methods using staining detection (minutes versus
      hours).

PMID- 15167776
TI  - Monitoring of bacterial contamination in food samples using capillary zone
      electrophoresis.
AB  - A capillary electrophoresis method with UV detection is proposed for the
      identification and quantitation of bacterial contamination in food samples. The
      electrophoretic separation relies on the differential mobility of bacteria in the
      capillary. Electrophoretic resolution is improved by using calcium and
      myoinositol hexakisphosphate as specific ions that interact with the bacterial
      surface changing its electrical properties and electrophoretic mobility. The
      proposed method allows the effective separation of eight different types of
      bacteria in only 25 min. It was successfully used to detect the presence of
      bacteria in contaminated food. The precision of the analysis of real spiked
      samples ranges from 3.3 to 7.0%, and the overall analysis time is 7 h, which is
      much shorter than the 24-48 h typically required for plate counts. The validity
      of the method was established by comparison with the standard plate counting
      method.

PMID- 15167777
TI  - Recirculation of nanoliter volumes within microfluidic channels.
AB  - A microfluidic device is described, capable of recirculating nanoliter volumes in
      restricted microchannel segments. The device consists of a PDMS microfluidic
      structure, reversibly sealed to a glass substrate with integrated platinum
      electrodes. The integrated electrodes generate electroosmotic flow locally, which
      results in a cycling flow in the channel segment between the two electrodes in
      case one channel exit is closed (dead-end channel). This cycling flow is a
      consequence of the counterbalancing hydrodynamic pressure against the
      electroosmotically generated flow. Acid-base indicators were employed to study
      the formation of H(+) and OH(-) at both the in-channel electrodes. The formation
      of acid can locally change the zeta-potential of the channel wall, which will
      affect the flow profile. Using this method, small analyte volumes can be mixed
      for prolonged times within well-defined channel segments and/or exposed to in
      channel sensor surfaces.

PMID- 15167778
TI  - Probing molecular dynamics in chromatographic systems using high-resolution 1H
      magic-angle-spinning NMR spectroscopy: interaction between p-Xylene and C18
      bonded silica.
AB  - The exact nature of the interaction between small molecules and chromatographic
      solid phases has been the subject of much research, but detailed understanding of
      the molecular dynamics in such systems remains elusive. High-resolution (1)H
      magic-angle-spinning (MAS) NMR spectroscopy has been applied to the investigation
      of C18-bonded silica material as used in chromatographic separation techniques
      together with an adsorbed model analyte, p-xylene. Two distinct p-xylene and
      water environments were identified within the C18-bonded silica through the
      measurement of (1)H NMR chemical shifts, T(1) and T(2) relaxation times and
      diffusion coefficients, including their temperature dependence. The results have
      been analyzed in terms of two environments, p-xylene within the C18 chains, in
      slow exchange on the NMR time scale with p-xylene in a more mobile state adsorbed
      as a layer in close proximity to the C18 particles, but which is distinct from
      free liquid p-xylene. The techniques used here could have more general
      applications, including the study of drug molecules bound into phospholipid
      membranes in micelles or vesicles.

PMID- 15167779
TI  - Absolute quantification of proteins in solutions and in polyacrylamide gels by
      mass spectrometry.
AB  - A combination of nanoelectrospray tandem mass spectrometry and (18)O-labeled
      peptide internal standards was applied for the absolute quantification of
      proteins from their in-solution and in-gel tryptic digests. Although absolute
      quantification from in-solution digests was accurate, we observed that in-gel
      digestion compromised the quantification accuracy by affecting the recovery of
      individual peptides and, therefore, the provided estimates might be strongly
      influenced by the selection of reference peptides. Under optimized experimental
      conditions, it was possible to provide a semiquantitative estimate of the
      absolute amount of gel separated proteins within better than 50% error margin.

PMID- 15167781
TI  - Chemical resolution of Pu+ from U+ and Am+ using a band-pass reaction cell
      inductively coupled plasma mass spectrometer.
AB  - Determination of the concentration and distribution of the Pu and Am isotopes is
      hindered by the isobaric overlaps between the elements themselves and U,
      generally requiring time-consuming chemical separation of the elements. A method
      is described in which chemical resolution of the elemental ions is obtained
      through ion-molecule reactions in a reaction cell of an ICPMS instrument. The
      reactions of "natural" U(+), (242)Pu(+), and (243)Am(+) with ethylene, carbon
      dioxide, and nitric oxide are reported. Since the net sensitivities to the
      isotopes of an element are similar, chemical resolution is inferred when one
      isobaric element reacts rapidly with a given gas and the isobar (or in this
      instance surrogate isotope) is unreactive or slowly reactive. Chemical resolution
      of the m/z 238 isotopes of U and Pu can be obtained using ethylene as a reaction
      gas, but little improvement in the resolution of the m/z 239 isobars is obtained.
      However, high efficiency of reaction of U(+) and UH(+) with CO(2), and
      nonreaction of Pu(+), allows the sub-ppt determination of (239)Pu, (240)Pu, and
      (242)Pu (single ppt for (238)Pu) in the presence of 7 orders of magnitude excess
      U matrix without prior chemical separation. Similarly, oxidation of Pu(+) by NO,
      and nonreaction of Am(+), permit chemical resolution of the isobars of Pu and Am
      over 2-3 orders of magnitude relative concentration. The method provides the
      potential for analysis of the actinides with reduced sample matrix separation.

PMID- 15167780
TI  - Aptamer-enhanced laser desorption/ionization for affinity mass spectrometry.
AB  - The thrombin-binding DNA aptamer was used for affinity capture of thrombin in
      MALDI-TOF-MS. The aptamer was covalently attached to the surface of a glass slide
      that served as the MALDI surface. Results show that thrombin is retained at the
      aptamer-modified surface while nonspecific proteins, such as albumin, are removed
      by rinsing with buffer. Upon application of the low-pH MALDI matrix, the G
      quartet structure of the aptamer unfolds, releasing the captured thrombin.
      Following TOF-MS analysis, residual matrix and protein can be washed from the
      surface, and buffer can be applied to refold the aptamers, allowing the surface
      to be reused. Selective capture of thrombin from mixtures of thrombin and albumin
      and of thrombin and prothrombin from human plasma was demonstrated. This simple
      approach to affinity capture, isolation, and detection holds potential for
      analysis, sensing, purification, and preconcentration of proteins in biological
      fluids.

PMID- 15167782
TI  - Trace detection of glycolic acid by electrophore labeling gas chromatography
      electron capture mass spectrometry.
AB  - As little as 10 pg of standard glycolic acid (glycolate) was detected in a method
      comprising the following sequence of steps: (1) add glycolate-2,2-d(2) as an
      internal standard and exchange the carboxylate oxygens in hot HCl/[(18)O]water;
      (2) form an amide derivative with a water-soluble carbodiimide and the
      electrophoric amine, AMACE1; (3) purify by bypass HPLC; (4) derivatize the
      residual hydroxy with butyric anhydride; (5) partition with acetonitrile/2 M
      NaCl; and (6) detect by GC-ECMS. At an intermediate stage in method development,
      1 pg of glycolate-2,2,-d(2) could be detected by subjecting it to the above steps
      2-6, forming product in an overall, absolute yield of 76%. Step 1 was added after
      an effort to fully overcome background contamination by glycolate was
      unsuccessful. For example, background contamination by glycolate could increase
      rather than decrease when the methanol reagent in the procedure was "carefully
      purified." The work extends the sensitivity for glycolate detection by
      approximately 100-fold and provides high-performance conditions for the
      analytical steps employed.

PMID- 15167783
TI  - Decoding two-dimensional complex multicomponent separations by autocovariance
      function.
AB  - A new method for decoding two-dimensional (2D) multicomponent separations based
      on the use of the 2D Autocovariance function (2D-ACVF) has been developed.
      Theoretical models of single component (SC) spot distributions in 2D separations,
      both random and structured, are developed as the basis for a nonlinear estimation
      of both sample and separation system parameters from experimental 2D separations.
      The number of SCs, the average spot size, the spot capacity, and the saturation
      factor can be evaluated in the case of random SC spot patterns. The procedure was
      validated by extensive numerical simulation under conditions close to those
      usually found in GC x GC or 2D-polyacrylamid gel electrophoresis of proteins. The
      worse precision degree was no greater than 10% in the case of maximum spot
      density. This imprecision was fully accounted for, and it seems acceptable owing
      to the intrinsic statistical character of the estimation method. Structured
      multicomponent 2D separations, where SCs are linked by linear relationships, give
      rise to specific structured patterns in 2D-ACVF plots from which the parameters
      (phase and frequency) of the structured SC sequences can be evaluated: the study
      of 2D-ACVF makes it possible to decode multicomponent 2D separation, that is, to
      determine the number, relative abundance, and structural similarities of the
      single components. Pertinent expressions of the theoretical 2D-ACVF were derived
      for simple cases, and a procedure for decoding cases of structured 2D separations
      was developed and applied. It was shown that 2D separations containing both
      random and structured patterns of SC spots give rise to 2D-EACVF, which is the
      superimposition of the two component parts. This feature allows one, in
      principle, to decode the two components. The relevance of these results for
      Giddings sample dimensionality and separation dimensionality and their effective
      experimental evaluation is discussed.

PMID- 15167784
TI  - Determination of pKa by pH gradient reversed-phase HPLC.
AB  - pH gradient reversed-phase HPLC consists of a programmed increase during the
      chromatographic run of the eluting power of the mobile phase with regard to
      ionizable analytes. On the analogy of the conventional organic modifier gradient
      RP HPLC, in the pH gradient mode, the eluting strength of the mobile phase
      increases due to its increasing (with acid analytes) or decreasing (with basic
      analytes) pH, whereas the content of organic modifier is kept constant. We have
      shown previously that the pH gradient separations are technically possible using
      standard chromatographic equipment. Here we demonstrate that the method is
      uniquely suitable to determine pK(a) values of analytes. A strict theoretical
      model is proposed to determine pK(a) values based on the retention data from a pH
      gradient RP HPLC run. The pK(a) data so obtained are discussed in relation to the
      concentration of methanol in the mobile phase, the type of stationary phase, and
      the duration of the gradient. The pK(a) values determined by the pH gradient
      method are related to the respective data obtained conventionally in a series of
      isocratic experiments. A close similarity of the two types of chromatographically
      determined pK(a) data is demonstrated. The HPLC-derived pK(a) parameters
      correlate to the literature pK(a) values determined by titrations in water. The
      chromatographically derived and the reference pK(a) values are not identical,
      however. That is probably due to the effects on the chromatographic pK(a) of the
      specific sites of interactions with analytes on the surfaces of the HPLC
      stationary phases. Nonetheless, the proposed pH gradient HPLC method may supply
      in a fast and convenient manner comparable acidity parameters for larger series
      of drug candidates, including those available in only minute amounts, without
      need of their purification, and also when the compounds are provided as complex
      mixtures, like those produced by combinatorial chemistry.

PMID- 15167785
TI  - Extraction of cesium ions from aqueous solutions using calix[4]arene-bis(tert
      octylbenzo-crown-6) in ionic liquids.
AB  - Solvent extraction of cesium ions from aqueous solution to hydrophobic ionic
      liquids without the introduction of an organophilic anion in the aqueous phase
      was demonstrated using calix[4]arene-bis(tert-octylbenzo-crown-6) (BOBCalixC6) as
      an extractant. The selectivity of this extraction process toward cesium ions and
      the use of a sacrificial cation exchanger (NaBPh(4)) to control loss of
      imidazolium cation to the aqueous solutions by ion exchange have been
      investigated.

PMID- 15167786
TI  - Cartesian-structure analysis in cast films by advanced infrared multiple-angle
      incidence resolution spectroscopy.
AB  - Multiple-angle incidence resolution spectroscopy (MAIRS) has been improved to be
      an advanced algorithm so that the Cartesian structure in organic thin films can
      be analyzed. The infrared MAIRS technique was originally proposed as a totally
      new spectroscopic technique to reveal structural anisotropy in thin films on an
      infrared-transparent substrate, which yields both in-plane- (IP; X and Y) and out
      of-plane (OP; Z)-mode spectra from an identical sample. Since this technique
      employs an analytical concept based on a signal decomposition of light intensity
      (not absorbance spectra), the algorithm intrinsically has high potential for
      further development. In the present study, the theoretically deduced matrix that
      correlates the light intensity to the angle of incidence has been modified to
      further decompose the IP-mode spectrum into X and Y components. As a result,
      anisotropic measurements of infrared spectra of thin film have become possible
      for the X, Y, and Z directions (Cartesian coordinate) simultaneously. With this
      advanced algorithm, the Cartesian structural changes in a cast film prepared on a
      germanium substrate have readily been analyzed, and a change from the biaxial to
      the uniaxial film structure with aging has spectroscopically been revealed.

PMID- 15167787
TI  - Generic lanthanide fluoroimmunoassay for the simultaneous screening of 18
      sulfonamides using an engineered antibody.
AB  - Sulfa antibiotics (sulfonamides) are used in veterinary and human medicine for
      therapeutic and prophylactic purposes. Veterinary use can result in foodstuffs
      derived from animals being contaminated with residual sulfonamides. Current
      sulfonamide-screening methods (mainly based on bacterial growth inhibition) are
      slow and inaccurate, since sensitivities of bacteria to different sulfonamides
      vary a lot. Therefore, a rapid immunoassay that was able to detect at least 18
      different sulfonamides at the MRL level (100 microg/kg) from food samples in a
      single reaction was developed. The assay was reproducible and adequately accurate
      for screening purposes. The presence of sulfonamide metabolites did not cause
      major assay interference. We also demonstrated reliable detection of sulfonamides
      from a panel of meat, milk, and serum samples with the assay.

PMID- 15167788
TI  - Multivariate calibration with least-squares support vector machines.
AB  - This paper proposes the use of least-squares support vector machines (LS-SVMs) as
      a relatively new nonlinear multivariate calibration method, capable of dealing
      with ill-posed problems. LS-SVMs are an extension of "traditional" SVMs that have
      been introduced recently in the field of chemistry and chemometrics. The
      advantages of SVM-based methods over many other methods are that these lead to
      global models that are often unique, and nonlinear regression can be performed
      easily as an extension to linear regression. An additional advantage of LS-SVM
      (compared to SVM) is that model calculation and optimization can be performed
      relatively fast. As a test case to study the use of LS-SVM, the well-known and
      important chemical problem is considered in which spectra are affected by
      nonlinear interferences. As one specific example, a commonly used case is studied
      in which near-infrared spectra are affected by temperature-induced spectral
      variation. Using this test case, model optimization, pruning, and model
      interpretation of the LS-SVM have been demonstrated. Furthermore, excellent
      performance of the LS-SVM, compared to other approaches, has been presented on
      the specific example. Therefore, it can be concluded that LS-SVMs can be seen as
      very promising techniques to solve ill-posed problems. Furthermore, these have
      been shown to lead to robust models in cases of spectral variations due to
      nonlinear interferences.

PMID- 15167790
TI  - Selective detection of glycopeptides on ion trap mass spectrometers.
AB  - Generation of carbohydrate-specific marker ions during LC-ESMS of digested
      glycoproteins has been demonstrated to be a highly selective and sensitive
      approach for detection of glycopeptides. In principle, any mass spectrometer can
      produce and selectively detect carbohydrate marker ions provided that the
      instrument is capable of collisional excitation in the region prior to the first
      mass analyzer sufficient to form abundant oxonium ions. This approach has yet to
      be demonstrated on 3D ion trap mass spectrometers, which have become widely used
      for proteomic applications. Here we report the successful development and
      optimization of carbohydrate marker ion detection on a LCQ Deca 3D ion trap
      utilizing this scan function. Human alpha-1 acid glycoprotein and a therapeutic
      monoclonal antibody were chosen to illustrate this methodology. Marker ion
      detection during LC-ESMS facilitated collection of glycopeptide-containing
      fractions. Analysis of the glycopeptides in these fractions by MS identified the
      specific glycosylation sites and enabled the prediction of the family of
      glycoforms at each attachment site. Using these optimized conditions, marker ion
      detection and glycopeptide analysis could be achieved with as little as 10 pmol
      of a glycoprotein.

PMID- 15167789
TI  - Use of polymer-modified MALDI-MS probes to improve analyses of protein digests
      and DNA.
AB  - The use of sample probe surfaces patterned with 200-microm-diameter spots of
      hydrophilic, charged polymers significantly enhances the analysis of protein
      digests and DNA by MALDI-MS. Selective adsorption on these polymer-modified
      surfaces allows collection of specific proteolytic peptides, while subsequent
      rinsing of the deposited sample removes contaminants. In the case of partially
      digested myoglobin, the mass spectrum obtained using a sample probe modified with
      polyanionic functionalities permits detection of 22 proteolytic fragments, while
      analysis using a stainless steel MALDI sample probe gives only 11 detectable
      fragments. Similarly, during the analysis of bovine serum albumin digests, the
      use of several different surface-modified MALDI sample probes increases sequence
      coverage from 61.3 to 74.5%. Detection of phosphorylated peptides can be quite
      challenging during analyses of phosphoprotein digests by MALDI-MS because these
      anionic proteolytic fragments have low ionization efficiencies. However, MALDI
      signals from the phosphorylated proteolytic fragments sometimes increase
      dramatically when using a sample probe surface modified by a polycation
      (polyethylenimine or poly(acrylic acid) complexed with Fe(3+)). The signal
      enhancement apparently occurs because the positive surface selectively binds the
      phosphorylated peptides. The use of patterned, polycationic surfaces also shows
      great promise for selective adsorption and decontamination of DNA samples; a
      simple water rinse diminishes or eliminates the formation of multi-ion adducts,
      thereby improving mass resolution during subsequent analysis by MALDI-MS.

PMID- 15167791
TI  - Multivariate pattern matching of trace elements in solids by laser ablation
      inductively coupled plasma-mass spectrometry: source attribution and preliminary
      diagnosis of fractionation.
AB  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is used
      with two variations of principal components analysis (PCA) for objective, routine
      comparisons of forensic materials without time-consuming and destructive sample
      dissolution. The relative concentrations of trace elements in a solid sample are
      examined to provide a "fingerprint" composition that can be used for
      identification and source matching of the material. Residue samples are matched
      to bulk materials using PCA. Variation of laser focus and PCA are also used to
      diagnose the severity of elemental fractionation in two metal samples that are
      prone to fractionation, brass and steel. Such fractionation remains the most
      significant limitation for accurate quantitative analyses by LA-ICPMS.

PMID- 15167792
TI  - Passive conductivity detection for capillary electrophoresis.
AB  - A passive electrochemical detection principle that can be applied to capillary
      electrophoresis is presented. The separation electrical field is used to generate
      a potential difference between two electrodes located along the channel. For
      constant-current electrophoresis, the generated signal is proportional to the
      resistance of the solution passing between the two electrodes. Contrary to
      conductivity detectors that are ac driven and need to be decoupled from the
      separation field, the passive detection directly takes advantage of the
      separation field. The signal is simply measured by a high-impedance voltmeter.
      The detection concept has been validated by numerical simulations showing how the
      magnitude of the signal is related to the ratio between the electrode distance
      and the length of the sample plug. As a proof of the principle, this detection
      concept has been demonstrated by the electrophoretic separation of three alkali
      ions on a polymer microchip. Based on preliminary results, a detection limit of
      20 microM and a dynamic range of up to 3 orders of magnitude have been achieved.

PMID- 15167793
TI  - Electrochemical DNA sensors based on enzyme dendritic architectures: an approach
      for enhanced sensitivity.
AB  - The modification of enzymes with multiple single-stranded oligonucleotides opens
      up a new concept for the development of DNA sensors with enhanced sensitivity.
      This work describes the generation of reporter sequences labeled with an enzyme
      for the demonstration of their ability to specifically hybridize and to permit
      signal amplification by successive hybridization steps. The synthetic pathway for
      the labeling of GOx with oligonucleotide sequences is based on the oxidation of
      the glycosidic residues of the enzyme and their covalent binding with 5'-end
      amine-modified oligonucleotides. Spectrophotometric characterization of these
      functionalized sequences results in an average number of three linked
      oligonucleotides per enzyme molecule. Their specificity is demonstrated in both a
      direct and a sandwich-type hybridization assay. The transduction of the enzyme
      linked DNA sensors is based on self-assembled multilayers, including a chemically
      modified anionic horseradish peroxidase electrochemically connected to a water
      soluble cationic poly[(vinylpyridine)Os(bpy)(2)Cl] redox polymer in an
      electrostatic ordered assembly. The sensing layer is constructed by the covalent
      binding of the DNA probe over the redox polymer through the 3'-phosphate group,
      enabling the capture of the target sequence. Upon addition of glucose,
      hybridization results in the production of H(2)O(2), which readily diffuses to
      the electrocatalytic assembly, giving rise to a cathodic current at 100 mV vs
      Ag/AgCl. Hybridization is always performed at room temperature, and after 30 min
      of incubation, an amperometric response is obtained that is proportional to DNA
      concentration. The simultaneous sandwich assay enables the quantification of a
      free-label 44-mer oligonucleotide at 1 nM concentration. Signal amplification is
      realized by a new hybridization step over the free sequences, giving rise to a
      dendritic architecture that accumulates enzyme molecules per hybridization event.

PMID- 15167794
TI  - Spectroelectrochemical sensing based on multimode selectivity simultaneously
      achievable in a single device. 17. Improvement in detection limits using
      ultrathin perfluorosulfonated ionomer films in conjunction with continuous sample
      flow.
AB  - We report herein an attenuated total reflectance (ATR) absorbance-based
      spectroelectrochemical sensor for tris(2,2'-bipyridyl)ruthenium(II) ion
      [Ru(bpy)(3)(2+)] that employs ultrathin (24-50 nm) Nafion films as the charge
      selective layer. This film serves to sequester and preconcentrate the analyte at
      the optically transparent electrode surface such that it can be efficiently
      detected optically via electrochemical modulation. Our studies indicate that use
      of ultrathin films in tandem with continuous flow of sample solution through the
      cell compartment leads to a 100-500-fold enhancement in detection limit (10 nM)
      compared to earlier absorbance-based spectroelectrochemical sensors (
      approximately 1-5 microM); markedly shorter analysis times also result. We report
      the dependence of the measured absorbance on sample flow rate and Nafion film
      thickness, and also provide calibration curves that illustrate the linear range
      and detection limits of the sensor using a 24 nm film at a constant sample flow
      rate of 0.07 mL/min.

PMID- 15167795
TI  - Scanning electrochemical microscopy of quinoprotein glucose dehydrogenase.
AB  - The activity of immobilized glucose dehydrogenase (GDH), a typical PQQ-dependent
      quinoprotein, was studied qualitatively and quantitatively by scanning
      electrochemical microscopy (SECM). PQQ-dependent GDH is of interest because of
      its high activity and independence of dissolved oxygen in catalyzing the transfer
      of electrons from glucose to an electron mediator. Biotinylated glucose
      dehydrogenase was bound to streptavidin-coated paramagnetic beads (surface
      concentration > or = 1.8 x 10(-11) mol cm(-2)) which were deposited as
      microscopic microspots on a hydrophobic surface. The catalytic activity of
      immobilized GDH was mapped in SECM feedback mode and generation-collection mode
      using ferrocenemethanol, ferrocenecarboxylic acid, p-aminophenol, and
      ferricyanide as electron mediators, respectively. The apparent steady-state
      kinetics of catalysis were measured under conditions of high d-glucose
      concentration using the theory developed for the SECM feedback and generation
      collection (GC) modes. In feedback mode, curves of the kinetically controlled
      substrate current against normalized distance were plotted, and it was found that
      GDH catalysis follows pseudo-first-order kinetics. In GC mode detection, the
      catalysis follows zero-order kinetics in the presence of high concentration of
      both substrates for GDH. The turnover rate obtained for immobilized GDH is lower
      than that of native GDH but much higher than that generally observed for glucose
      oxidase.

PMID- 15167798
TI  - Model selection and optimal sampling in high-throughput experimentation.
AB  - The practical difficulties encountered in analyzing the kinetics of new reactions
      are considered from the viewpoint of the capabilities of state-of-the-art high
      throughput systems. There are three problems. The first problem is that of model
      selection, i.e., choosing the correct reaction rate law. The second problem is
      how to obtain good estimates of the reaction parameters using only a small number
      of samples once a kinetic model is selected. The third problem is how to perform
      both functions using just one small set of measurements. To solve the first
      problem, we present an optimal sampling protocol to choose the correct kinetic
      model for a given reaction, based on T-optimal design. This protocol is then
      tested for the case of second-order and pseudo-first-order reactions using both
      experiments and computer simulations. To solve the second problem, we derive the
      information function for second-order reactions and use this function to find the
      optimal sampling points for estimating the kinetic constants. The third problem
      is further complicated by the fact that the optimal measurement times for
      determining the correct kinetic model differ from those needed to obtain good
      estimates of the kinetic constants. To solve this problem, we propose a Pareto
      optimal approach that can be tuned to give the set of best possible solutions for
      the two criteria. One important advantage of this approach is that it enables the
      integration of a priori knowledge into the workflow.

PMID- 15167796
TI  - On-line coupling of high-performance liquid chromatography to a continuous-flow
      enzyme assay based on electrospray ionization mass spectrometry.
AB  - Liquid chromatography (LC) was coupled on-line to a continuous-flow enzymatic
      assay using electrospray ionization mass spectrometry (ESI-MS) as readout for the
      screening of enzyme inhibitors in complex samples. Inhibitors were detected by
      changes in the concentration of the enzymatic reaction products, indicating the
      inhibition of enzymatic activity. The molecular masses of the inhibitors were
      determined with high certainty by using retention time matching and peak shape
      comparison. Due to the high matching accuracy, baseline separation of coeluting
      analytes was not necessary in order to identify the correct masses of the
      bioactive compounds. The continuous-flow system was successfully applied for the
      screening of complex samples, such as natural extracts. For a red clover extract,
      detection limits of 0.3-0.8 micromol/L were obtained. System validation was
      performed by determining the IC(50) values of four inhibitors in the flow
      injection mode. The IC(50) values were in the 0.11-5.6 micromol/L range and
      correspond closely to data obtained by microtiter plate assays. Detection limits
      were in the range of 0.018-0.35 micromol/L in the flow-injection mode, and 0.075
      0.75 micromol/L in the LC mode. These values are well below the typical compound
      concentrations (1-10 micromol/L) used in high-throughput screening. Together with
      an interday precision of 12.6%, these results demonstrate the applicability of
      the system for bioactivity screening of complex mixtures, generating both
      chemical and biological information on bioactive compounds in a single run.

PMID- 15167797
TI  - Integrated portable genetic analysis microsystem for pathogen/infectious disease
      detection.
AB  - An integrated portable genetic analysis microsystem including PCR amplification
      and capillary electrophoretic (CE) analysis coupled with a compact instrument for
      electrical control and laser-excited fluorescence detection has been developed.
      The microdevice contains microfabricated heaters, temperature sensors, and
      membrane valves to provide controlled sample positioning and immobilization in
      200-nL PCR chambers. The instrument incorporates a solid-state laser and confocal
      fluorescence detection optics, electronics for sensing and powering the PCR
      reactor, and high-voltage power supplies for conducting CE separations. The
      fluorescein-labeled PCR products are amplified and electrophoretically analyzed
      in a gel-filled microchannel in <10 min. We demonstrate the utility of this
      instrument by performing pathogen detection and genotyping directly from whole
      Escherichia coli and Staphylococcus aureus cells. The E. coli detection assay
      consists of a triplex PCR amplification targeting genes that encode 16S ribosomal
      RNA, the fliC flagellar antigen, and the sltI shigatoxin. Serial dilution
      demonstrates a limit of detection of 2-3 bacterial cells. The S. aureus assay
      uses a femA marker to identify cells as S. aureus and a mecA marker to probe for
      methicillin resistance. This integrated portable genomic analysis microsystem
      demonstrates the feasibility of performing rapid high-quality detection of
      pathogens and their antimicrobial drug resistance.

PMID- 15167799
TI  - Photoionization pathways and free electrons in UV-MALDI.
AB  - The recently developed model for primary and secondary UV-MALDI ion formation
      (Knochenmuss, R. J. Mass Spectrom. 2002, 37, 867-877. Knochenmuss, R. Anal. Chem.
      2003, 75, 2199.) is applied to questions regarding photoionization pathways and
      electron versus negative ion production. Two-photon ionization of the matrix in
      direct contact with analyte is possible under some circumstances (Kinsel, G.;
      Knochenmuss, R.; Setz, P.; Land, C. M.; Goh, S.-K.; Archibong, E. F.; Hardesty,
      J. H.; Marynik, D. J. Mass Spectrom. 2002, 37, 1131-1140.), and is added to the
      model. When analyte is present in large mole ratios (such as when matrix
      suppression is desired), this effect contributes modestly to the ion yield.
      Generally, matrix exciton pooling remains dominant. The interfacial layer of thin
      samples on a metal substrate may also be ionizable in a 2-photon process. A
      mechanism is proposed, and the correspondingly modified model gives excellent
      agreement with electron emission versus laser intensity data. Capture in, or
      escape of low-energy electrons from a thick sample (or on a nonmetallic
      substrate) is also examined. Because the mean free path for MALDI electrons in a
      solid matrix is on the order of 10 nm, below such depths, any electrons generated
      are captured to form negative ions. Only a surface layer can emit free electrons.
      This surface emission effect is also well reproduced by the model, up to a laser
      intensity limit caused by surface charging. This charging phenomenon is
      investigated and illustrated by molecular dynamics calculations.

PMID- 15167800
TI  - In situ spectral monitoring of mRNA translation in embryonic stem cells during
      differentiation in vitro.
AB  - Raman microspectroscopy was used to determine biochemical markers during the
      differentiation of embryonic murine stem cells (mES) in vitro. Such markers are
      useful to determine the differentiation status of ES cells cultured on
      biomaterials. Raman spectra of mES cells as undifferentiated, spontaneously
      differentiated (4 days), and differentiated cells via formation of embryoid
      bodies (16, 20 days) were analyzed. Unsupervised hierarchical cluster analysis
      and principal component analysis were used to determine biochemical differences
      between mES cells in various states of differentiation. The undifferentiated
      cells were characterized by high scores of the first principal component (PC1,
      49% variance). Similarity between the PC1 loading and the Raman spectrum of RNA
      indicated a high concentration of RNA in mES cells compared to differentiated
      cells. The ratio between the peak areas of RNA and proteins was used as a measure
      of mRNA translation. Using the same peak area ratio, it was possible to
      differentiate even between mES as undifferentiated and in early stages of
      differentiation (4 days). These findings were correlated with biological studies
      reporting high levels of nontranslated mRNA during early embryonic development.
      Therefore, the RNA translation obtained from the Raman spectra can be used as
      marker of differentiation state of mES cells.

PMID- 15167801
TI  - Micromechanical detection of proteins using aptamer-based receptor molecules.
AB  - We report label-free protein detection using a microfabricated cantilever-based
      sensor that is functionalized with DNA aptamers to act as receptor molecules. The
      sensor utilizes two adjacent cantilevers that constitute a sensor/reference pair
      and allows direct detection of the differential bending between the two
      cantilevers. One cantilever is functionalized with aptamers selected for Taq DNA
      polymerase while the other is blocked with single-stranded DNA. We have found
      that the polymerase-aptamer binding induces a change in surface stress, which
      causes a differential cantilever bending that ranges from 3 to 32 nm depending on
      the ligand concentration. Protein recognition on the sensor surface is specific
      and has a concentration dependence that is similar to that in solution.

PMID- 15167803
TI  - Heterogeneous surface charge enhanced micromixing for electrokinetic flows.
AB  - Enhancing the species mixing in microfluidic applications is key to reducing
      analysis time and increasing device portability. The mixing in electroosmotic
      flow is usually diffusion-dominated. Recent numerical studies have indicated that
      the introduction of electrically charged surface heterogeneities may augment
      mixing efficiencies by creating localized regions of flow circulation. In this
      study, we experimentally visualized the effects of surface charge patterning and
      developed an optimized electrokinetic micromixer applicable to the low Reynolds
      number regime. Using the optimized micromixer, mixing efficiencies were improved
      between 22 and 68% for the applied potentials ranging from 70 to 555 V/cm when
      compared with the negatively charged homogeneous case. For producing a 95%
      mixture, this equates to a potential decrease in the required mixing channel
      length of up to 88% for flows with Peclet numbers between 190 and 1500.

PMID- 15167802
TI  - Depth profiling of 4-acetamindophenol-doped poly(lactic acid) films using cluster
      secondary ion mass spectrometry.
AB  - The feasibility of using cluster secondary ion mass spectrometry for depth
      profiling of drug delivery systems is explored. The behavior of various
      biodegradable polymer films under dynamic SF(5)(+) primary ion bombardment was
      investigated, including several films doped with model drugs. The SF(5)(+) depth
      profiles obtained from these biodegradable polymer films showed very little
      degradation in secondary ion signal as a function of increasing primary ion dose,
      and it was discovered that the characteristic ion signals for the polymers
      remained constant for ion doses up to approximately 5 x 10(15) ions/cm(2). These
      results suggest that the polyester structure of the biodegradable polymers
      studied here allows for a greater ability to depth profile due to ease of main
      chain scission. Attempts were also made to depth profile through a series of
      poly(lactic acid) (PLA) films containing varying concentrations of the drug 4
      acetamidophenol. The depth profiles obtained from these films show very little
      decrease in both the 4-acetamidophenol molecular ion and PLA fragment ion signals
      as a function of increasing SF(5)(+) primary ion dose. Similar results were
      obtained with theophylline-doped PLA films. These results show that, in some drug
      delivery devices, it is possible to monitor the distribution of a drug as a
      function of depth by using cluster primary ion beams.

PMID- 15167804
TI  - Comparison of Hadamard transform and signal-averaged detection for microchannel
      electrophoresis.
AB  - A Hadamard transform (HT) detection method for microchip capillary
      electrophoresis with laser-induced fluorescence and a charge-coupled device (CCD)
      is described and compared to signal-averaged detection. A low-noise CCD camera is
      used to image a section of a separation channel where each camera pixel can be
      thought of as a unique detector. For signal averaging, electropherograms
      corresponding to individual pixels can be averaged for improved S/N. HT detection
      is performed on each pixel electropherogram to generate a contour plot
      electropherogram. The multiple injections required for HT provides an enhancement
      at the cost of longer times for the pseudorandom injection sequences. A short
      sample injection length of 0.25 s is used to reduce the overall analysis time and
      improve sensitivity compared to previously published results. An injection
      sequence is performed on the microchip that is based on a cyclic S-matrix of 513
      elements that generates an 8-fold improvement in S/N compared to a single
      injection. This spatially resolved HT detection method is also capable of
      performing a multicomponent separation. Signal-averaged HT and single-injection
      data are compared to experimental HT and single-injection results. The unique
      capabilities of each method are described.

PMID- 15167805
TI  - Capillary-assembled microchip for universal integration of various chemical
      functions onto a single microfluidic device.
AB  - A novel concept for assembling various chemical functions onto a single
      microfluidic device is proposed. The concept, called a capillary-assembled
      microchip, involves embedding chemically functionalized capillaries into a
      lattice microchannel network fabricated on poly(dimethylsiloxane) (PDMS). The
      network has the same channel dimensions as the outer dimensions of the
      capillaries. In this paper, we focus on square capillaries to be embedded into a
      PDMS microchannel network having a square cross section. The combination of hard
      glass square capillary and soft square PDMS channel allows successful fabrication
      of a microfluidic device without any solution leakage, and which can use
      diffusion-based two-solution mixing. Two different types of chemically modified
      capillaries, an ion-sensing capillary and a pH-sensing capillary, are prepared by
      coating a hydrophobic plasticized poly(vinyl chloride) membrane and a hydrophilic
      poly(ethyleneglycol) membrane containing functional molecules onto the inner
      surface of capillaries. Then, they are cut into appropriate lengths and arranged
      on a single microchip to prepare a dual-analyte sensing system. The concept
      proposed here offers advantages inherent to using a planar microfluidic device
      and of chemical functionality of immobilized molecules. Therefore, we expect to
      fabricate various types of chemically functionalized microfluidic devices soon.

PMID- 15167806
TI  - Printed circuit technology for fabrication of plastic-based microfluidic devices.
AB  - One of the primary advantages of using plastic-based substrates for microfluidic
      systems is the ease with which devices can be fabricated with minimal dependence
      on specialized laboratory equipment. These devices are often produced using soft
      lithography techniques to cast replicas of a rigid mold or master incorporating a
      negative image of the desired surface structures. Conventional photolithographic
      micromachining processes are typically used to construct these masters in either
      thick photoresist, etched silicon, or etched glass substrates. The speed at which
      new masters can be produced using these techniques, however, can be relatively
      slow and often limits the rate at which new device designs can be built and
      tested. In this paper, we show that inexpensive photosensitized copper clad
      circuit board substrates can be employed to produce master molds using
      conventional printed circuit technology. This process offers the benefits of
      parallel fabrication associated with photolithography without the need for
      cleanroom facilities, thereby providing a degree of speed and simplicity that
      allows microfluidic master molds with well-defined and reproducible structural
      features to be constructed in approximately 30 min in any laboratory. Precise
      control of channel heights ranging from 15 to 120 microm can be easily achieved
      through selection of the appropriate copper layer thickness, and channel widths
      as small as 50 microm can be reproducibly obtained. We use these masters to
      produce a variety of plastic-based microfluidic channel networks and demonstrate
      their suitability for DNA electrophoresis and microfluidic mixing studies.

PMID- 15167807
TI  - Pinched inlet split flow thin fractionation for continuous particle
      fractionation: application to marine sediments for size-dependent analysis of
      PCDD/Fs and metals.
AB  - It is demonstrated that split-flow thin (SPLITT) fractionation, a continuous
      separation technique for sorting particles or macromolecules, can be utilized for
      the fractionation of environmental particles to study a size-dependent analysis
      of pollutants. In this study, focuses are made on the use of a pinched inlet
      gravitational SPLITT fractionation, a modified form of SPLITT channel formed by
      reducing the sample inlet thickness of the channel to improve separation
      efficiency, to separate marine sediments into five different sizes (<1.0,
      approximately 1.0 to 2.5, approximately 2.5 to 5.0, approximately 5.0 to 10, and
      approximately 10 to 53 microm). The resulting size fractions are examined with
      high resolution gas chromatography/high resolution mass spectrometry to determine
      the size-dependent distribution of polychlorinated dibenzo-p-dioxins and
      dibenzofurans along with a statistical data treatment and are analyzed with
      inductively coupled plasma-atomic emission spectrometry and graphite furnace
      atomic absorption spectrometry to ascertain its major and trace metals. It is
      shown that the combined analytical methods detailed in this study can be
      powerfully utilized in such a way as to analyze pollutant distribution and its
      concentration with regard to particle sizes for an environmental assessment.

PMID- 15167808
TI  - Chemical reversibility and stable low-potential NADH detection with
      nonconventional conducting polymer nanotubule modified glassy carbon electrodes.
AB  - Studies of the oxidation of beta-nicotinamide adenine dinucleotide (NADH) at
      glassy carbon (GCEs) electrode surfaces, modified with nonconventional conducting
      polymer nanotubules, are reported. In contrast to the situation with conventional
      carbon electrodes, chemical reversibility of the NADH oxidation reaction was
      achieved by means of poly(1,2-diaminobenzene) conducting nanotubule coatings. A
      Delta E(p) of 425 mV (vs Ag/AgCl; pH 7.0) was observed. The NADH amperometric
      response of the conducting nanotubule modified GCEs was shown to be extremely
      stable, with 98% of the initial response remaining after 48 h of stirring in the
      presence of 1 x 10(-4) M NADH solutions (compared to 14% at the poly(1,2
      diaminobenzene) modified GCEs). The nonconventional conducting polymer nanotubule
      coated electrodes, when tested in amperometric mode for NADH electrochemical
      oxidation at an applied potential of 450 mV, showed a sensitivity of 99 nA/mM, an
      operational stability for 2 days, a storage stability of 2 weeks at 4 degrees C,
      a linearity from 5 x 10(-5) to 1 x 10(-3) M, and good NADH chemical
      reversibility, all of which make them useful tools for dehydrogenase enzyme probe
      assembly.

PMID- 15167811
TI  - Tumour necrosis factor alpha decreases glucose-6-phosphatase gene expression by
      activation of nuclear factor kappaB.
AB  - The key insulin-regulated gluconeogenic enzyme G6Pase (glucose-6-phosphatase) has
      an important function in the control of hepatic glucose production. Here we
      examined the inhibition of G6Pase gene transcription by TNF (tumour necrosis
      factor) in H4IIE hepatoma cells. TNF decreased dexamethasone/dibtuyryl cAMP
      induced G6Pase mRNA levels. TNFalpha, but not insulin, led to rapid activation of
      NFkappaB (nuclear factor kappaB). The adenoviral overexpression of a dominant
      negative mutant of IkappaBalpha (inhibitor of NFkappaB alpha) prevented the
      suppression of G6Pase expression by TNFalpha, but did not affect that by insulin.
      The regulation of G6Pase by TNF was not mediated by activation of the
      phosphoinositide 3-kinase/protein kinase B pathway, extracellular-signal
      regulated protein kinase or p38 mitogen-activated protein kinase. Reporter gene
      assays demonstrated a concentration-dependent down-regulation of G6Pase promoter
      activity by the transient overexpression of NFkappaB. Although two binding sites
      for NFkappaB were identified within the G6Pase promoter, neither of these sites,
      nor the insulin response unit or binding sites for Sp proteins, was necessary for
      the regulation of G6Pase promoter activity by TNFalpha. In conclusion, the data
      indicate that the activation of NFkappaB is sufficient to suppress G6Pase gene
      expression, and is required for the regulation by TNFalpha, but not by insulin.
      We propose that NFkappaB does not act by binding directly to the G6Pase promoter.

PMID- 15167812
TI  - A call for an evidence-based evaluation of late midtrimester abortion.

PMID- 15167813
TI  - Oxidative stress in preeclampsia.

PMID- 15167814
TI  - Cervicovaginal cytokines, vaginal infection, and preterm birth.

PMID- 15167815
TI  - Dilation and evacuation at >or=20 weeks: comparison of operative techniques.
AB  - OBJECTIVE: The objective of this study is to compare the relative safety of 2
      techniques for surgical abortion late in the second trimester.Study design
      Retrospective review of patients who underwent surgical abortion at >or=20 weeks'
      gestation at our hospital from June 1996 through June 2003. Records were reviewed
      to determine whether the technique used was dilation and evacuation or intact
      dilation and extraction. Subsequent pregnancies at our hospital were identified,
      and obstetric outcomes were recorded. Categorical data were compared with Fisher
      exact test and chi(2) analysis. Continuous data were compared with Mann-Whitney U
      test. RESULTS: Three hundred eighty-three patients met inclusion criteria. Intact
      dilation and extraction was performed in 120 cases, and dilation and evacuation
      was used in 263. Intact dilation and extraction was associated with higher
      parity, later gestational age, and more preoperative cervical dilation. There was
      no difference in procedure time or estimated blood loss in the 2 groups.
      Complications occurred in 19 cases (5.0%), and occurred with similar frequency in
      the 2 groups. We identified 62 subsequent pregnancies. There were no second
      trimester miscarriages. Spontaneous preterm birth occurred in 2 of 17 (11.8%)
      pregnancies in the intact dilation and extraction group, compared with 2 of 45
      (4.4%) in the dilation and evacuation group (P=.30). CONCLUSION: Outcomes appear
      similar between patients undergoing dilation and evacuation and intact dilation
      and extraction after 20 weeks' gestation. Subsequent obstetric outcomes are
      similar between the 2 groups. The technique for surgical abortion should be
      determined by the physician on the basis of intraoperative factors.

PMID- 15167810
TI  - Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse
      cellular processes.
AB  - 14-3-3 proteins exert an extraordinarily widespread influence on cellular
      processes in all eukaryotes. They operate by binding to specific phosphorylated
      sites on diverse target proteins, thereby forcing conformational changes or
      influencing interactions between their targets and other molecules. In these
      ways, 14-3-3s 'finish the job' when phosphorylation alone lacks the power to
      drive changes in the activities of intracellular proteins. By interacting
      dynamically with phosphorylated proteins, 14-3-3s often trigger events that
      promote cell survival--in situations from preventing metabolic imbalances caused
      by sudden darkness in leaves to mammalian cell-survival responses to growth
      factors. Recent work linking specific 14-3-3 isoforms to genetic disorders and
      cancers, and the cellular effects of 14-3-3 agonists and antagonists, indicate
      that the cellular complement of 14-3-3 proteins may integrate the specificity and
      strength of signalling through to different cellular responses.

PMID- 15167816
TI  - Increased breath markers of oxidative stress in normal pregnancy and in
      preeclampsia.
AB  - OBJECTIVES: The purpose of this study was to compare the intensity of oxidative
      stress in normal pregnancy, preeclampsia, and nonpregnant women using a breath
      test. STUDY DESIGN: We studied primiparous women in third trimester pregnancy (38
      uncomplicated, 26 with preeclampsia) and 60 nonpregnant control subjects.
      Volatile organic compounds (VOCs) in alveolar breath were analyzed by gas
      chromatography/mass spectroscopy to construct the breath methylated alkane
      contour (BMAC), a 3-dimensional display of abundance of C4-C20 alkanes and
      monomethylated alkanes. RESULTS: The mean volume under curve (VUC) of the BMAC
      was significantly higher in preeclampsia patients than in normal pregnant women
      (P < .003) and nonpregnant control subjects (P < .005). A predictive model
      employing 5 VOCs distinguished preeclampsia from uncomplicated pregnancy
      (sensitivity = 92.3%, specificity = 89.7%; cross-validated sensitivity = 88.5%,
      specificity = 79.3%). CONCLUSION: A breath test significantly demonstrated
      greater oxidative stress in women with preeclampsia than in uncomplicated
      pregnancy and nonpregnant control subjects. The breath test accurately identified
      women with established preeclampsia, but further studies are required to
      determine if this test can predict the onset of disease.

PMID- 15167817
TI  - A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal
      secretions of pregnant women with altered vaginal microflora correlates with
      preterm birth.
AB  - OBJECTIVE: This purpose of this study was to investigate the association between
      vaginal microflora, concentrations of interleukin-1beta (IL-1beta), and its
      natural receptor antagonist (IL-1ra) in the cervicovaginal discharge, and
      spontaneous preterm birth. Study design Vaginal samples collected at 18 to 22
      weeks' gestation from 207 women were analyzed to study qualitative and
      quantitative microbiologic aspects of vaginal microflora and IL-1beta and IL-1ra
      concentrations. RESULTS: Among women colonized with anaerobic Gram-negative rods
      and/or Gardnerella vaginalis, an elevated IL-1beta concentration, or a diminished
      IL-1ra:IL-1beta ratio were associated with preterm delivery. A cut-off IL-1ra:IL
      1beta ratio of <8632:1 optimally discriminated the subjects with subsequent
      spontaneous preterm deliveries from subjects who delivered at term, with a
      sensitivity of 78%, specificity of 51%, positive predictive value of 21%, and
      negative predictive value of 95%. CONCLUSION: A disproportionate increase in IL
      1beta over IL-1ra in response to vaginal colonization with anaerobic Gram
      negative rods and/or G. vaginalis at 18 to 22 weeks' gestation is associated with
      spontaneous preterm delivery.

PMID- 15167818
TI  - Neglected ethical dimensions of the professional liability crisis.
AB  - In response to the professional liability crisis, self-interest can become
      dominant and displace fiduciary professionalism from its central place in the
      moral lives of physicians and physician leaders. We provide preventive ethics
      tools to address this neglected ethical dimension of the professional liability
      crisis. We develop these tools on the basis of the concept of the physician as
      fiduciary of the patient, which was introduced in the English-language literature
      of medical ethics by Dr John Gregory (1714-1773). These tools are designed to
      preserve and strengthen 4 professional virtues: integrity, compassion, self
      effacement, and self-sacrifice. Acceptable and unacceptable responses to the
      professional liability crisis are identified with the use of these 4 virtues.
      These virtues should be supported by an organizational culture of fiduciary
      professionalism. An organizational culture that is shaped by these 4 professional
      virtues should be used by physicians and physician leaders to create ethical best
      practice models.

PMID- 15167819
TI  - Effect of pregnancy and stage of pregnancy on asthma severity: a systematic
      review.
AB  - Although pregnancy is purported to affect maternal asthma, the literature has not
      been reviewed systematically. The purpose of this systematic review was to
      determine, among pregnant women with asthma, whether pregnancy and stage of
      pregnancy influence maternal asthma severity. Six electronic databases were
      searched in January 2003 for prospective studies of currently asthmatic, pregnant
      women who were enrolled before the third trimester and assessed with objective
      measures of asthma severity or validated severity scales. Three studies reported
      54 pregnant women with asthma who met the inclusion criteria. The most valid
      study indicated that bronchial hyperresponsiveness to methacholine improved
      between preconception and pregnancy in 69% of the women, although it deteriorated
      in 31% of the women. Further, this improvement peaked in the second trimester,
      reverted after delivery, and was greatest among those women who were most
      hyperresponsive initially. Lung function also showed a trend towards improvement
      during pregnancy that was not significant. Large, well-conducted population-based
      studies that explore different aspects of asthma severity are needed to
      substantiate these preliminary results.

PMID- 15167820
TI  - The risks of underwater birth.
AB  - OBJECTIVE: We performed a retrospective review of the literature on the
      complications that could be associated potentially with water birth. STUDY
      DESIGN: We performed an extensive review of the medical literature using the Pub
      Med search engine, which is available through the National Library of Medicine.
      We also examined the Cochrane review on immersion in pregnancy, labor and birth.
      RESULTS: Our review revealed 74 articles regarding water births. We found 16
      citations that described complications that were associated with underwater
      birth. Possible complications that were associated with water birth included
      fresh water drowning, neonatal hyponatremia, neonatal waterborne infectious
      disease, cord rupture with neonatal hemorrhage, hypoxic ischemic encephalopathy,
      and death. Our systematic review did not identify an adequately controlled trial
      of delivery underwater (second stage of labor underwater) compared with delivery
      in air. CONCLUSION: Water birth may be associated with potential complications
      that are not seen with land-based birth. The rates of these complications are
      likely to be low but are not well defined.

PMID- 15167822
TI  - Menorrhagia II: is the 80-mL blood loss criterion useful in management of
      complaint of menorrhagia?
AB  - OBJECTIVE: Menorrhagia is defined in terms of statistical"abnormality"as blood
      loss of >80 mL. We examined the usefulness of this definition in women who were
      referred to gynecology clinics with heavy periods. STUDY DESIGN: A questionnaire
      survey of 952 menstrual complaint referrals at 3 hospital gynaecology clinics in
      Glasgow and Edinburgh included 226 women with heavy periods who had also
      consented to the measurement of their blood loss. RESULTS: Women reported a range
      of problems with their periods, but absolute volume (31.2%) was less prevalent
      than period pain (37.5%), mood change (35.7%), and change in the amount (volume)
      of the period (33.8%). Although there were associations with volume, these
      associations were due to the heaviest and lightest of the loss groups, whereas
      the 2 groups with loss either side of 80 mL were virtually indistinguishable.
      CONCLUSION: The 80-mL criterion for menorrhagia is of limited clinical usefulness
      because it is prognostic neither for problems nor iron status and apparently does
      not guide management.

PMID- 15167821
TI  - Menorrhagia I: measured blood loss, clinical features, and outcome in women with
      heavy periods: a survey with follow-up data.
AB  - OBJECTIVE: Menorrhagia is defined as blood loss of >80 mL, but in routine
      clinical practice measurement is seldom undertaken. Our aim was to identify the
      features of the clinical history that best predict menorrhagic blood loss. STUDY
      DESIGN: A questionnaire survey of 952 menstrual complaint referrals at 3 hospital
      gynecology clinics in Glasgow and Edinburgh included 226 women with putatively
      heavy periods who also had consented to the measurement of their blood loss.
      RESULTS: Only 34% (95% CI, 28%-40%) of women had blood loss volume of >80 mL, but
      the volume was associated with subjective heaviness of period. Logistic
      regression with ferritin status, clots, and changing rate during full flow
      correctly predicts a loss of >80 mL for 76% of women (n=161 patients;
      sensitivity, 60%; specificity, 86%). Diagnosis and treatment of patients seem
      unrelated to the volume of blood loss. CONCLUSION: The subjective judgment of the
      volume of blood loss is better than has been believed. Clinical features can be
      combined to predict losses of >80 mL.

PMID- 15167823
TI  - Persistent vaginal discharge after uterine artery embolization for fibroid
      tumors: cause of the condition, magnetic resonance imaging appearance, and
      surgical treatment.
AB  - OBJECTIVE: The purpose of this study was to establish the cause of and treatment
      for chronic vaginal discharge after uterine artery embolization. STUDY DESIGN:
      This was a retrospective review of the diagnosis and treatment of the procedure
      at 3 months. RESULTS: In 94% of patients, the condition either completely
      resolved or diminished to a nonproblematic level. CONCLUSION: The persistent
      discharge in these patients was due to a superficial cavity within the infarcted
      fibroid tumor that was communicating with the endometrial cavity through a hole
      in the endometrium. This situation is indicated by a specific appearance on TII
      sagittal magnetic resonance images. Hysteroscopic resection of the necrotic
      fibroid tumor cavity was usually curative.

PMID- 15167824
TI  - A study of female urinary tract infection caused by urodynamic investigation.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of female
      urinary tract infection before and after urodynamic investigation and to identify
      the risk factors for urinary tract infection after urodynamic investigation.
      STUDY DESIGN: Eight hundred twenty-two consecutive incontinent women were
      recruited. All women were "double-screened" and treated for urinary tract
      infection before urodynamic investigation: first by mid stream urine culture 4 to
      6 weeks before investigation and then by reagent strips for urine leukocytes and
      nitrites at the time of investigation. The investigation was postponed until the
      urinary tract infection had been treated. All women then received a standard
      urodynamic investigation. RESULTS: The prevalence of urinary tract infection
      before urodynamic investigation was 5.1% (95% CI, 3.6-6.6), and the prevalence
      after the investigation was 8.4% (95% CI, 6.5-10.3). Three independent risk
      factors were identified: age >or=70 years (odds ratio, 1.99; 95% CI, 1.14-3.48),
      previous continence surgery (odds ratio, 1.90; 95% CI, 1.05-3.43), and urinary
      tract infection before urodynamic investigation (odds ratio, 3.13; 95% CI, 1.43
      6.83). The 3 most common uropathogens in the urinary tract infections after the
      urodynamic investigation were Escherichia coli (46.3%), Enterococcus spp (16.4%),
      and Enterococcus faecalis (11.9%). CONCLUSION: Despite a stringent screen-and
      treat protocol before urodynamic investigation, patients still experienced
      urinary tract infection.

PMID- 15167825
TI  - Effect of antiretroviral therapy on the incidence of genital warts and vulvar
      neoplasia among women with the human immunodeficiency virus.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and
      predictors of genital warts and vulvar intraepithelial neoplasia among women with
      the human immunodeficiency virus. STUDY DESIGN: This was a multicenter
      prospective cohort study comprised of women without warts or vulvar
      intraepithelial neoplasia at baseline who underwent CD4 count, human
      immunodeficiency virus RNA measurement, examination, Papanicolaou test, and
      biopsy, as indicated, every 6 months. Human papillomavirus DNA typing was
      examined at baseline. RESULTS: The incidence of warts among women who were human
      immunodeficiency virus seronegative was 1.31 versus 5.01 per 100 person-years
      among women who were seropositive (P < .001). Incidence of vulvar intraepithelial
      neoplasia among women who were seronegative was 1.31 versus 4.67 per 100 person
      years among women who were seropositive (P < .001). In multivariable analysis,
      warts were associated with highly active antiretroviral therapy (relative hazard,
      0.76), CD4 count (relative hazard, 0.91/100 cell/cm(2) increase), acquired
      immunodeficiency syndrome (relative hazard, 1.25), abnormal Papanicolaou test
      results (relative hazard, 2.18), high- or medium-risk human papillomavirus types
      (relative hazard, 1.91), low-risk human papillomavirus types (relative hazard,
      1.48), smoking (relative hazard, 1.43), having 1 child (relative hazard, 1.54),
      and age (relative hazard, 0.74/10 years). Vulvar intraepithelial neoplasia was
      linked to highly active antiretroviral therapy (relative hazard, 0.65), CD4 count
      (relative hazard, 0.92), abnormal Papanicolaou test results (relative hazard,
      16.03), high- or medium-risk human papillomavirus types (relative hazard, 1.37),
      and age (relative hazard, 0.85/10 years). CONCLUSION: Warts and vulvar
      intraepithelial neoplasia are common among women with human immunodeficiency
      virus. Highly active antiretroviral therapy decreases their incidence.

PMID- 15167826
TI  - Optical detection of high-grade cervical intraepithelial neoplasia in vivo:
      results of a 604-patient study.
AB  - OBJECTIVE: The purpose of this study was to assess the in vivo optical detection
      of high-grade cervical intraepithelial neoplasia (2/3+) on the whole cervix with
      a noncontact, spectroscopic device. STUDY DESIGN: Cervical scanning devices
      collected intrinsic fluorescence and broadband white light spectra and video
      images from 604 women during routine colposcopy examinations at 6 clinical
      centers. A statistically significant dataset was developed of intrinsic
      fluorescence and white light-induced cervical tissue spectra that was correlated
      to expert histopathologic determination. On the basis of a retrospective analysis
      of the acquired data, a classification algorithm was developed, validated, and
      optimized. RESULTS: Intrinsic fluorescence, backscattered white light, and video
      imaging each contribute complementary information to diagnostic algorithms for
      high-grade cervical neoplasia. More than 10000 measurements that were made on
      colposcopically identified tissue from >500 subjects were the basis for algorithm
      training and testing. Algorithm performance demonstrated a sensitivity of
      approximately 90%. This performance was confirmed by various training methods.
      With the use of a multivariate classification algorithm, optical detection is
      predicted to detect 33% more high-grade cervical intraepithelial neoplasia (2/3+)
      than colposcopy alone. CONCLUSION: Full cervix optical interrogation for the
      detection of high-grade cervical intraepithelial neoplasia is feasible and
      appears capable of detecting more high-grade cervical intraepithelial neoplasia
      than colposcopy alone. With the use of this classification algorithm, a
      multisite, randomized controlled trial is underway that compares the combination
      of optical detection and colposcopy versus colposcopy alone.

PMID- 15167827
TI  - Activation of invasiveness of cervical carcinoma cells by angiotensin II.
AB  - OBJECTIVE: Angiotensin II recently has been reported to promote the growth of
      several kinds of cells. In this study, we investigated the effect of angiotensin
      II on cervical carcinoma cells. STUDY DESIGN: The expression of angiotensin II
      type I receptor was examined by immunohistochemistry in normal and neoplastic
      cervical tissues. Invasion assay was examined in Siha cells (cervical squamous
      cell carcinoma) and vascular endothelial growth factor levels were assayed with a
      vascular endothelial growth factor enzyme-linked immunosorbent assay kit.
      RESULTS: Mean staining intensity level was stronger in invasive carcinoma cells
      than in normal, dysplasia, and carcinoma in situ tissues. Angiotensin II induced
      the secretion of vascular endothelial growth factor from Siha cells. Furthermore,
      angiotensin II promoted the invasive potential of Siha cells. These effects were
      reversed by the addition of anti-human vascular endothelial growth factor
      antibody and candesartan (antagonist of angiotensin II type I receptor).
      CONCLUSION: Angiotensin II is involved in the progression of cervical carcinoma,
      because it induces the secretion of vascular endothelial growth factor through
      angiotensin II type I receptor, which results in the increased invasiveness of
      carcinoma cells.

PMID- 15167828
TI  - Symptoms before and after surgical removal of colorectal endometriosis that are
      assessed by magnetic resonance imaging and rectal endoscopic sonography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of colorectal
      resection for endometriosis on symptoms and quality of life or on potential side
      effects. STUDY DESIGN: After magnetic resonance imaging and rectal endoscopic
      sonographic evaluations of symptomatic colorectal endometriosis, 27 consecutive
      women who underwent colorectal resection were included in this prospective study.
      They completed symptom questionnaires before and after the procedure. Linear pain
      scores for several gynecologic and digestive symptoms and impact on quality of
      life were recorded. RESULTS: The sensitivity and positive predictive value of
      magnetic resonance imaging and rectal endoscopic sonographic evaluation for the
      diagnosis of colorectal endometriosis were 92.6% and 100% and 89% and 100%,
      respectively. Nonmenstrual pelvic pain (P = .001), dysmenorrhea (P < .0001),
      dyspareunia (P = .0002), and pain on defecation (P < .005) were improved by
      colorectal resection. No correlation was found between symptom intensity and
      lesion size, as evaluated by magnetic resonance imaging, rectal endoscopic
      sonographic evaluation, or histologic examination of the surgical specimen.
      Respectively, the conditions of 14, 11, 0, and 2 women were cured, improved,
      unchanged, or worsened. Median overall pre- and postoperative quality-of-life
      scores were 9 (range, 4-10) and 0 (range, 0-10), respectively (P < .0001).
      CONCLUSION: Colorectal resection for endometriosis appears to relieve some
      symptoms. However, women should be informed that some symptoms may persist and
      that there is a risk of urinary and digestive side effects.

PMID- 15167829
TI  - Vaginal pH is similar to follicle-stimulating hormone for menopause diagnosis.
AB  - OBJECTIVE: This paper is intended to demonstrate whether vaginal pH value is
      associated with menopausal status and symptoms, to review the sensitivity of
      follicle-stimulating hormone or vaginal pH to diagnose menopause, to compare
      these findings to a group of practice patients, and to determine whether vaginal
      pH could be used in place of follicle-stimulating hormone as an initial screen to
      determine menopause. STUDY DESIGN: Sixteen studies regarding vaginal pH and
      menopausal symptoms before and after estrogen administration were analyzed. Two
      epidemiologic studies that reported follicle-stimulating hormone or vaginal pH
      with menopause were reviewed. These findings were compared with similar data from
      the practice of one of the authors (J.C.C.). RESULTS: Menopausal women who do not
      receive estrogen therapy have a weighted average vaginal pH of 6.0, which is
      reduced significantly to 4.5 with estrogen therapy. To diagnose menopause,
      follicle-stimulating hormone >or=15 or >or=20 mIU/mL in the Third National Health
      and Nutrition Examination Survey had a sensitivity of 65% to 68%. In a study in
      Costa Rica, where 3 definitions of menopause were used, a pH of >5.0 had a
      sensitivity of 64% to 67%. From the practice patients, the 95% confidence
      interval sensitivities and positive predictive values of vaginal pH and follicle
      stimulating hormone to diagnose menopause overlapped, while a pH <or=4.5
      indicated mid follicular phase estradiol levels. CONCLUSION: In women without
      vaginitis and no estrogen therapy, a vaginal pH of > 4.5 indicates menopause,
      because it demonstrates a similar sensitivity as follicle-stimulating hormone in
      epidemiologic studies. In the practice patients, the sensitivity of follicle
      stimulating hormone was no different than vaginal pH in the diagnosis of
      menopause. Furthermore, with estrogen therapy, a vaginal pH of <or=4.5 indicates
      a mid follicular phase estradiol.

PMID- 15167830
TI  - Comparative study of MMP-2 (matrix metalloproteinase 2) immune expression in
      normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical
      carcinoma.
AB  - OBJECTIVE: This study was undertaken to evaluate the levels of matrix
      metalloproteinase 2 (MMP-2) in the precursors lesions and in the invasive
      cervical carcinoma and to quantify the immune reactive expression of MMP-2, using
      MMP-2 immunohistochemistry, in intraepithelial cervical neoplasias and in the
      invading cervical carcinoma. STUDY DESIGN: We evaluated 60 samples of cervical
      tissues using immunohistochemistry for MMP-2 in 5 distinct groups. The groups
      were divided in control, cervical intraepithelial neoplasia I (CIN I), CIN II,
      CIN III, and cervical invading carcinoma. RESULTS: MMP-2 expression was found
      gradually increased according to the degree of cervical intraepithelial neoplasia
      and cervical carcinoma. (Control<CIN I<CIN II<CIN III<Carcinoma) CONCLUSION: Our
      results suggest that the expression of MMP-2 can distinguish CIN I, II, and III
      grades and the invading carcinoma.

PMID- 15167831
TI  - Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent
      relaxation of myometrial small arteries.
AB  - OBJECTIVE: In preeclampsia, endothelium-dependent function is markedly aberrant.
      Myometrial resistance arteries from women with preeclampsia show a minimal,
      wholly nitric oxide-mediated, bradykinin-induced relaxation. Our aim was to test
      that phosphodiesterase 5 (PDE5) inhibition could improve endothelium-dependent
      function in preeclampsia. Study design Small arteries dissected from myometrial
      biopsies obtained at cesarean section from normal pregnant women (N=22) or women
      with preeclampsia (N=24) were mounted on wire or pressure myographs. Vessels were
      constricted (arginine vasopressin or U46619) and relaxed (bradykinin) before and
      after incubation with a PDE5 inhibitor, UK-343664. RESULTS: Endothelium-dependent
      vasodilatation was decreased in vessels from women with preeclampsia. 100 nmol/L
      UK-343664 did not affect normal pregnant but significantly improved relaxation of
      the vessels from women with preeclampsia. CONCLUSION: A PDE5 inhibitor enhances
      endothelial function of myometrial vessels from women with preeclampsia, such
      that the behavior of these arteries approximates to those from normal women.
      These agents offer a potential therapeutic strategy for the management of
      preeclampsia.

PMID- 15167832
TI  - Effects of combined use of sildenafil citrate (Viagra) and 17beta-estradiol on
      ovine coronary and uterine hemodynamics.
AB  - OBJECTIVE: This study was undertaken to determine whether Viagra (Pfizer, New
      York, NY), a type 5 phosphodiesterase (PDE-5) inhibitor, increases baseline
      coronary and uterine blood flow or potentiates estrogen-induced increases in
      blood flow. STUDY DESIGN: Seven nonpregnant ovariectomized ewes were chronically
      instrumented to measure blood pressure, heart rate, cardiac output, and coronary
      and uterine blood flow. Estradiol-17beta (E2, 0.3 microg/kg) (Sigma Chemical Co,
      St Louis, Mo) and Viagra (50 mg) were intravenously administered separately or
      together and hemodynamic responses monitored. RESULTS: Viagra alone rapidly
      decreased mean arterial pressure and cardiac output while increasing heart rate
      and uterine blood flow. Viagra tended to decrease coronary blood flow but not
      significantly. E2 by itself increased coronary and uterine blood flow over a 2
      hour time course, whereas mean arterial pressure, cardiac output, and heart rate
      remained unchanged. Administration of E2 to animals pretreated with Viagra
      reversed Viagra-related decrease in cardiac output and coronary blood flow,
      resulting in a time-related increase in both parameters over baseline values.
      Viagra significantly augmented estradiol-related increases in uterine blood flow.
      CONCLUSION: In our surgically menopausal ovine model, Viagra alone has a tendency
      to decrease baseline coronary blood flow, but the reduction does not reach
      statistical significance. The presence of estradiol reverses this Viagra-related
      negative trend and results in a net increase in coronary blood flow and cardiac
      output. Furthermore, Viagra significantly augments baseline and estrogen-induced
      increases in uterine blood flow suggesting the presence of PDE-5 in the ovine
      uterine vasculature.

PMID- 15167833
TI  - Reproductive health history of lesbians: implications for care.
AB  - OBJECTIVE: Parity and hormonal contraceptives modify the risk of reproductive
      cancers and cardiovascular disease. However, clinicians may not obtain
      reproductive histories from patients who self-identify as lesbian. We report
      lifetime pregnancy-related outcomes and hormonal contraception for 392 women who
      reported sexual activity with another woman in the preceding year. STUDY DESIGN:
      Among self-referred volunteers, previous pregnancy, pregnancy outcome,
      contraceptive use, and sexual identity were assessed with self-administered
      questionnaire. RESULTS: One in 4 subjects had been pregnant, and more than 50% of
      the women had used oral contraceptives (mean duration, 40 months). Sixteen
      percent of all subjects and 63% of those who had been pregnant previously
      reported having 1 or more induced abortions. The most common pregnancy outcome
      for women younger than 25 years was induced abortion (59% of pregnancies).
      Identifying as "lesbian" or "bisexual" predicted neither the duration of oral
      contraceptive use nor a report of induced abortion. CONCLUSION: Previous
      pregnancy, induced abortion, and hormonal contraceptive use are common among
      women who report sex with women, regardless of self-identification as lesbian.

PMID- 15167834
TI  - Intrauterine repair of spina bifida: preoperative predictors of shunt-dependent
      hydrocephalus.
AB  - OBJECTIVE: The objective of this study was to determine which factors that are
      present at the time of intrauterine repair of spina bifida could predict the need
      for ventriculoperitoneal shunt for hydrocephalus during the first year of life.
      STUDY DESIGN: One hundred seventy-eight fetuses have undergone intrauterine
      repair of spina bifida at Vanderbilt University Medical Center since 1997. Among
      these, 116 fetuses had a postnatal follow-up period of at least 12 months. The
      primary outcome of the study was the need for a ventriculoperitoneal shunt for
      hydrocephalus during the first year of life. The following variables were
      analyzed: maternal demographics (age, race, gravidity, and parity), gestational
      age at the time of surgery, ventricular size, degree of hindbrain herniation
      (determined by magnetic resonance imaging in 33 cases), type of defect
      (myelomeningocele vs myeloschisis), upper level of the lesion, presence of
      talipes, and intraoperative use of a lumbar drain. Statistical analysis was
      performed with logistic regression (to test the association of fetal and maternal
      factors and the need for ventriculoperitoneal shunting), 2-sample t-tests for
      comparison of means, and receiver operating curves with the use of the
      probabilities that were generated by the logistic regression for both continuous
      and categoric versions of the factors. RESULTS: Sixty-one of 116 of the fetuses
      (54%) who underwent operation in utero required the placement of a
      ventriculoperitoneal shunt before the age of 1 year. The upper level of the
      lesion was the strongest predictor of shunt requirement (adjusted odds ratio per
      1 level increase with the use of continuous variables [S1 through T10], 1.73 [95%
      CI, 1.22- 2.44]; adjusted odds ratio with the use of upper lesion level >or=L3 vs
      <L3 as a categorized variable, 5.7 [95% CI, 2.18- 14.7]), followed by gestational
      age at the time of surgery (adjusted odds ratio per 1 week increase with the use
      of continuous variables, 1.37 [95% CI, 1.06-1.77]; adjusted odds ratio with the
      use of gestational age <or=25 weeks vs >25 weeks as a categorized variable, 3.3
      [95% CI, 1.28-8.24]), and preoperative ventricular size (adjusted odds ratio per
      1 unit increase with the use of continuous variables, 1.17 [95% CI, 1.01-1.36];
      adjusted odds ratio with the use of ventricular size >or=14 mm vs <14 mm as a
      categorized variable, 3.5 [95% CI, 1.08-11.16]). Receiver operating curves with
      the use of the probabilities that were generated by the logistic regression
      analyses for both the continuous and categoric versions of the factors were
      compared. The area under the curve was approximately 0.81 for both methods.
      Thirty-eight of 48 of the fetuses (79%) with an upper level of the lesion >or=L3
      required placement of a ventriculoperitoneal shunt, although 25 of 68 of the
      fetuses (37%) with lesions <or=L4 did not (P < .0001). Eighty-four percent of the
      fetuses with a preoperative ventricular size >or=14 mm (27/32 fetuses) needed a
      shunt compared with 41% of the fetuses (34/81 fetuses) with smaller ventricles
      (P=.03). Seventy-one percent of the fetuses who underwent operation at >25 weeks
      of gestation also required shunt placement (37/52 fetuses); 39% of the fetuses
      (24/61 fetuses) who were treated <or=25 weeks of gestation did not (P=.01).
      Thirty-five fetuses had a lesion level <or=L4 and a ventricular size <14 mm and
      underwent operation at <or=25 weeks of gestation. Among these, 8 fetuses (23%)
      required a ventriculoperitoneal shunt during the first year of life. CONCLUSION:
      This study suggests that, among fetuses who underwent operation in utero for
      spina bifida, fetuses with a ventricular size of <14 mm at the time of surgery,
      fetuses who had surgery at <or=25 weeks of gestation, and fetuses with defects
      that were located at <or=L4 were less likely to require ventriculoperitoneal
      shunting for hydrocephalus during the first year of life.

PMID- 15167836
TI  - Fetal sex and indicated very preterm birth: results of the EPIPAGE study.
AB  - OBJECTIVE: This study was undertaken to explore the association between fetal
      sex, mode of onset of labor, and principal cause of very preterm birth. Study
      design The analysis uses data on 2624 very preterm singleton births less than 33
      weeks' gestation from a prospective study of all very preterm births in 9 French
      regions in 1997. RESULTS: Fifty-seven percent of the spontaneous births were male
      versus 50.8% of births after medical decision (P=.005). This pattern was
      explained by sex differences in causes of preterm birth. Male infants had a
      greater incidence of very preterm birth after spontaneous labor (relative risk
      [RR]=1.42 [1.21-1.66]), but one third less risk of indicated preterm birth
      associated with hypertension both with and without growth restriction (RR=0.73
      [0.55-0.97] and 0.77 [0.60-0.97]). CONCLUSION: These results support previous
      reports of greater male susceptibility to preterm labor. The finding that
      pregnancies carrying female infants have a greater predisposition to indicated
      very preterm birth associated with hypertension has not been reported previously
      and merits further study.

PMID- 15167835
TI  - Trends in twin neonatal mortality rates in the United States, 1989 through 1999:
      influence of birth registration and obstetric intervention.
AB  - OBJECTIVE: We sought to evaluate the contributions of changes in birth
      registration, labor induction, and cesarean delivery on trends in twin neonatal
      mortality rates. STUDY DESIGN: We conducted a population-based, retrospective
      cohort study of twin live births, using linked birth-infant death data in the
      United States (1989-1999). Relative risks and 95% confidence intervals that
      quantified changes in neonatal (0-27 days) mortality rates were derived from
      ecologic logistic regression models that were fit after aggregation of the data
      by each state in the United States. RESULTS: The frequency of live born twins who
      weighed <500 g increased 72%, from 0.7% in 1989 to 1.2% in 1999, of live born
      twins who weighed 500 to 749 g and 750 to 999 g increased by 55% and 28%,
      respectively, between 1989 and 1999. Preterm birth rates increased by 19%, from
      46.2% in 1989 to 57.2% in 1999. The rate of labor induction increased from 5.8%
      to 13.9%, and the cesarean delivery rate increased from 49.8% to 56.3%. Between
      1989 to 1991 and 1997 to 1999, the crude neonatal mortality rates among twins who
      weighed >or=500 g declined by 37% (95% CI, 35%-40%) from 21.5 to 13.6 per 1000
      twin live births. Adjustments for preterm labor induction, preterm cesarean
      delivery, term labor induction, term cesarean delivery, and sociodemographic
      factors had little influence on neonatal mortality rate trends. CONCLUSION:
      Increases in preterm birth because of obstetric intervention among twins have not
      led to increases in twin neonatal mortality rates in the United States.

PMID- 15167837
TI  - A dilated fetal stomach predicts a complicated postnatal course in cases of
      prenatally diagnosed gastroschisis.
AB  - OBJECTIVE: The purpose of this study was to determine whether dilation of the
      fetal stomach is associated with increased perinatal complications in infants
      with prenatally diagnosed gastroschisis. STUDY DESIGN: From 34 newborn infants
      with gastroschisis who were delivered at our institution over a 10-year period, 2
      groups were analyzed on the basis of the presence or absence of a dilated fetal
      stomach. Reactive versus nonreactive nonstress test results were recorded, when
      performed. Neonatal outcomes were compared. RESULTS: Twenty-one fetuses had no
      evidence of gastric dilation. Thirteen fetuses had a dilated fetal stomach that
      was identified by ultrasound scanning. Within this group there was a higher
      incidence of nonreactive nonstress tests (P=.01). Infants with a prenatally
      dilated stomach had a higher incidence of volvulus and neonatal death, a
      significantly delayed time to full oral feeds, and a longer hospitalization than
      those infants who did not have a prenatally dilated stomach (P <or=.05).
      CONCLUSION: Postnatal morbidity and mortality rates are increased in infants with
      gastroschisis who have a prenatally dilated stomach. These fetuses, although not
      acidotic at delivery, also had a higher incidence of nonreactive nonstress test
      results.

PMID- 15167838
TI  - Maternal and perinatal outcome in women with a history of stroke.
AB  - OBJECTIVE: The purpose of this study was to determine recurrence risk and
      pregnancy outcome in 23 women with a history of stroke. STUDY DESIGN: We
      conducted a descriptive study of 23 women (35 pregnancies) with a history of
      stroke. Charts were reviewed from 1990 through 2002. The data were analyzed for
      the antenatal treatment strategies, recurrence risk for stroke, and pregnancy
      outcome. RESULTS: There were 23 study patients with 35 subsequent pregnancies.
      Associated risk factors of the stroke were thrombophilia (5 women), sickle cell
      disease (3 women), maternal cardiac malformations (3 women), hypertension (3
      women), oral contraceptive use (2 women), cerebral arteriovenous malformations (2
      women), head trauma (1 woman), meningitis (1 woman), endocarditis (1 woman), and
      idiopathic reason (2 women). Four women with 9 subsequent pregnancies had a
      stroke that was associated with a previous pregnancy or postpartum incident. Two
      of these 9 pregnancies received anticoagulation (heparin, 1 pregnancy; heparin
      plus aspirin, 1 pregnancy). Nineteen women with 26 subsequent pregnancies had a
      stroke before pregnancy. Nine of these 26 pregnancies received anticoagulation
      (heparin, 5 pregnancies; aspirin, 3 pregnancies; heparin plus aspirin, 1
      pregnancy). The remaining pregnancies did not receive prophylactic
      anticoagulation. Overall, there were 21 term deliveries, 8 preterm deliveries, 5
      miscarriages, and 1 fetal death. Three of 34 pregnancies (9%) were small for
      gestational age infants. There were no recurrent thrombotic episodes during
      pregnancy or after delivery. Maternal complications included admission to the
      intensive care unit for uncontrolled hypertension in 1 patient. CONCLUSION: Women
      with a history of stroke have a low risk of recurrent stroke (0%). This
      information is useful for the prepregnancy counseling of such individuals. The
      need for prophylactic anticoagulation in patients with a previous stroke cannot
      be answered by this study.

PMID- 15167839
TI  - Pregnancy after bariatric surgery is not associated with adverse perinatal
      outcome.
AB  - OBJECTIVE: The purpose of this study was to investigate the pregnancy outcome of
      patients after bariatric surgery. STUDY DESIGN: A population-based study was
      performed that compared all pregnancies of patients with and without previous
      obesity operations between the years 1988 and 2002. Stratified analyses with the
      Mantel-Haenszel technique and a multiple logistic regression model were performed
      to control for confounders. RESULTS: Of the 159210 deliveries that were performed
      during the study period, 298 deliveries were to patients after bariatric
      operations. No significant differences regarding obstetric characteristics or
      pregnancy outcome were noted between the open (n=159) and laparoscopic procedures
      (n=139). With the use of a multivariable analysis, the following conditions were
      associated significantly with a previous bariatric operation: previous cesarean
      delivery (odds ratios, 1.4; 95% confidence interval, 1.1-2.0; P=.024), fertility
      treatments (odds ratios, 2.3; 95% confidence interval, 1.6-3.8; P<.001),
      premature rupture of membranes (odds ratios, 1.9; 95% confidence interval, 1.3
      2.7; P=.001), labor induction (odds ratios, 2.1; 95% confidence interval, 1.6
      2.7; P<.001), fetal macrosomia (birth weight, >4 kg; odds ratios, 2.1; 95%
      confidence interval, 1.4-3.0; P<.001), and obesity (odds ratios, 8.8; 95%
      confidence interval, 6.1-12.9; P<.001). No significant differences were noted
      between the groups regarding other pregnancy complications such as placental
      abruption, placenta previa, labor dystocia, or perinatal complications (such as
      meconium-stained amniotic fluid, perinatal mortality, congenital malformations
      and low Apgar scores at 1 and 5 minutes). However, there were higher rates of
      cesarean delivery among the bariatric operation group (25.2% vs 12.2%; odds
      ratios, 2.4; 95% confidence interval, 1.9-3.1; P <.001). When controlled for
      possible confounders (such as previous cesarean delivery, obesity, fertility
      treatments, premature rupture of membranes, labor induction, diabetes mellitus,
      hypertensive disorders and fetal macrosomia) by the Mantel-Haenszel technique,
      the correlation between previous bariatric surgery and cesarean delivery remained
      significant. CONCLUSION: Previous bariatric surgery, although an independent risk
      factor for cesarean delivery, is not associated with adverse perinatal outcome.

PMID- 15167840
TI  - A hospital-sponsored quality improvement study of pain management after cesarean
      delivery.
AB  - OBJECTIVE: We undertook this study to systematically assess prevailing pain
      management regimes used at our hospital in women after cesarean delivery. STUDY
      DESIGN: Between August 1999 and July 2000, all women delivered by cesarean
      section at Parkland Hospital were assigned to 1 of 4 different pain management
      strategies: (1). intramuscular (IM) meperidine, (2). patient-controlled analgesia
      (PCA) meperidine, (3). IM morphine sulfate, and (4). PCA morphine sulfate. A
      combination of methods were used to compare these different pain management
      strategies. A survey questionnaire, using Likert scale responses, was
      administered to evaluate maternal satisfaction with pain control. Visual Analog
      Scale (VAS) scores and information regarding breastfeeding and rooming-in were
      also collected. RESULTS: A total of 1256 women were allocated to the 4 analgesia
      study groups. The median meperidine dosages for the IM and PCA groups were 350 mg
      and 600 mg, respectively (P <or=.01). Conversely, the median IM morphine dose (65
      mg) was significantly higher than that for the PCA group (60 mg). The percentage
      of women reporting moderate or worse pain (VAS scores 4 or more) was
      significantly lower in those women who received PCA meperidine compared with IM
      meperidine. Women who received morphine reported less severe pain compared with
      meperidine, regardless of route of administration. The patients' subjective
      report of satisfaction with pain management was not related to the method or drug
      used for pain control (P=.13). Fewer women assigned to morphine therapy stopped
      breastfeeding (P=.02) and more roomed-in with their infants (P <.01). CONCLUSION:
      Pain relief was superior with the morphine regimens used and was positively
      associated with breastfeeding and infant rooming-in.

PMID- 15167841
TI  - Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus
      blood flow in growth-restricted human fetuses.
AB  - OBJECTIVE: The purpose of this study was to evaluate the changes in the
      distribution of the umbilical venous blood flow to the liver and to the ductus
      venosus in intrauterine growth-restricted human fetuses in relationship with
      dilation of the ductal isthmic diameter. STUDY DESIGN: Umbilical venous flow,
      ductus venosus blood flow, and blood flow to the fetal liver were measured in 56
      severely intrauterine growth-restricted fetuses with an abnormal pulsatility
      index of the umbilical artery and were compared with 137 normal control fetuses.
      Percentages of umbilical venous blood flow through the ductus venosus and to the
      fetal hepatic lobes were calculated. Z-scores for control fetuses and
      intrauterine growth-restricted fetuses were constructed by the evaluation of the
      inverted smoothed percentiles. The distributions of the Z-scores was compared
      with a 1-sample t-test. RESULTS: The ductus venosus blood flow that was corrected
      for fetal weight was increased significantly in intrauterine growth-restricted
      fetuses compared with control fetuses (P=0); the median values (interquartile
      range) for comparable ages of gestation was 41.3 mL/min/kg (range, 26.2-64.0
      mL/min/kg) and 30.8 mL/min/kg (range, 19.9-42.8 mL/min/kg), respectively. As a
      consequence, ductus venosus shunting was increased in intrauterine growth
      restricted fetuses compared with control fetuses (P =0). In 23 of 30 intrauterine
      growth-restricted fetuses, the percentage of umbilical blood flow that was
      shunted through the ductus was>90th percentile of control fetuses. Ductal
      diameters were significantly greater in growth-restricted fetuses than in control
      fetuses (P =.0001). The percentage of blood flow to the right lobe showed a
      significant reduction (P =.0223), with evidence of reversed blood flow from the
      right lobe and portal system into the ductus venosus that was provided both by
      volume blood flow calculations and by direct pulsed Doppler waveform direction.
      CONCLUSION: In severe intrauterine growth-restricted fetuses, Doppler examination
      of blood flow volume proved a significant increase in the shunting of umbilical
      vein blood flow through the ductus venosus that was associated with the dilation
      of the ductal isthmic diameter. These changes provide a relatively constant blood
      flow to the heart and brain at the expense of fetal hepatic perfusion.

PMID- 15167842
TI  - Maternal birth weight in relation to plasma lipid concentrations in early
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine the extent to which, if at
      all, maternal weight at birth is related to dyslipidemia during early pregnancy,
      which is a risk factor for preeclampsia. STUDY DESIGN: This hospital-based
      prospective cohort study included 1000 women who initiated prenatal care before
      16 weeks of gestation. Participants provided information about their birth weight
      and other sociodemographic and reproductive covariates. Plasma triglyceride, high
      density lipoprotein cholesterol, and total cholesterol concentrations were
      measured at approximately 13 weeks of gestation. beta coefficients and standard
      errors were estimated by multiple linear regression; odds ratios and 95%
      confidence intervals were estimated by logistic regression. RESULTS: Maternal
      birth weight was correlated negatively with triglycerides (r =-0.12; P =.001) and
      was correlated positively with high-density lipoprotein cholesterol (r =0.08; p
      =.02) but not statistically significantly related with total cholesterol (r =
      0.004; P=.91). After adjusting for potential confounders, women who weighed <2500
      g at birth had higher triglyceride and total cholesterol concentrations
      (beta=23.4 mg/dL [P<.001]; beta =2.6 mg/dL [P =.585], respectively) and lower
      high-density lipoprotein cholesterol concentrations (beta =-3.2 mg/dL; P=.105),
      when compared with women who weighed 3000 to 3499 g at birth. Women who were born
      small (<2500 g) and became overweight (body mass index, >or=25 kg/m(2)) in
      adulthood had less favorable lipid profiles than their counterparts who weighed
      >or=2500 g at birth and remained lean (body mass index, <25 kg/m(2)). CONCLUSION:
      Our findings suggest that factors that are related to growth in utero may help to
      predict the subsequent risk of altered lipid metabolism during pregnancy, which
      may, in turn, be causally related to the occurrence of preeclampsia.

PMID- 15167843
TI  - Oral docosahexaenoic acid given to pregnant mice increases the amount of
      surfactant in lung and amniotic fluid in preterm fetuses.
AB  - OBJECTIVE: Our purpose was to determine whether docosahexaenoic acid increased
      surfactant production, as reflected by increased dipalmitoyl phosphatidylcholine,
      in mouse fetal lung and amniotic fluid. STUDY DESIGN: On day 9.5 of gestation,
      pregnant mice were given docosahexaenoic acid orally at 0, 5, 10, or 20 mg per
      day and were killed at day 16.5 (preterm) and day 19.5 (term) of gestation.
      Dipalmitoyl phosphatidylcholine was measured in fetal lung homogenates and
      amniotic fluid by high-performance thin-layer chromatography. RESULTS:
      Dipalmitoyl phosphatidylcholine values in lung were 0.22 +/- 0.27 microg/mg of
      total protein in preterm versus 1.96 +/- 0.57 microg/mg in term control fetuses.
      Pretreatment with 5, 10, or 20 mg docosahexaenoic acid increased dipalmitoyl
      phosphatidylcholine levels in preterm fetuses to 1.20 +/- 0.75, 1.60 +/- 0.67,
      and 3.28 +/- 0.44 microg/mg of protein, respectively. A similar trend was
      observed in amniotic fluid in which dipalmitoyl phosphatidylcholine levels were
      1.86 +/- 3.70 microg/mL in preterm fetuses at baseline and increased to 7.81 +/-
      1.21, 16.83 +/- 1.62 and 22.72 +/- 3.44 microg/mL after pretreatment for 7 days
      with 5, 10, and 20 mg docosahexaenoic acid (P<.05 compared to untreated mice).
      Dipalmitoyl phosphatidylcholine levels in amniotic fluid were 24.46 +/- 10.3
      microg/mL in term control mice. CONCLUSION: The oral administration of
      docosahexaenoic acid to pregnant mice during pregnancy can induce dipalmitoyl
      phosphatidylcholine production and secretion, which is the major lipid component
      of surfactant.

PMID- 15167844
TI  - Incorporating problem-based learning into an obstetrics/gynecology clerkship:
      impact on student satisfaction and grades.
AB  - OBJECTIVE: The purpose of this study was to describe the effect of the problem
      based learning method on student grade and on student and faculty satisfaction.
      STUDY DESIGN: The problem-based learning method was instituted at 2 of 5
      obstetrics/gynecology clerkship sites. Students and faculty were surveyed, with
      the use of a Likert scale, regarding aspects of satisfaction with the clerkship.
      Responses were compared according to problem-based learning usage. Student
      performance was also assessed according to problem-based learning usage, with a
      comparison of several grade components. Statistical analysis involved t-tests and
      Kendall's tau-C. RESULTS: For the year that was assessed, 54 of 156 students used
      the problem-based learning method. Mean student satisfaction responses were
      significantly higher for students who used the problem-based learning method.
      Faculty satisfaction was also significantly higher for the problem-based learning
      method, compared with other teaching methods. Mean scores on the National Board
      of Medical Examiners subject examination were higher for problem-based learning
      but did not reach statistical significance. Grade distribution was not
      significantly different for the groups. CONCLUSION: The problem-based learning
      method was associated with improved student and faculty satisfaction and did not
      affect student grades negatively.

PMID- 15167845
TI  - Outcomes of teaching medical students core skills for women's health: the pelvic
      examination educational program.
AB  - OBJECTIVE: The purpose of this study was to evaluate the outcomes of introducing
      an educational program that teaches medical students how to approach taking
      relevant and sensitive gynecologic histories and to perform pelvic examinations
      with the use of role-play with well women from the general community. STUDY
      DESIGN: Medical students and the women recorded their perceptions of the program
      over a 2-year period. The outcomes of the program were evaluated by a comparison
      of medical student perceptions of confidence, competence, and anxiety; the mean
      number of pelvic examinations that were performed during their course both before
      and after the introduction of the program and results of students' continuous and
      summative assessment are given. RESULTS: In the year before the introduction of
      the program, students performed a mean of 2.6 pelvic examinations (95% CI, 2.1,
      3.0) compared with 4.1 pelvic examination (95% CI, 3.8, 4.4) in the first year of
      implementation and 4.0 (95% CI, 3.7, 4.3) in the second year of implementation (P
      <.05). Students reported improved competence and reduced anxiety to perform a
      pelvic examination without supervision (P <.05). All students passed their
      continuous assessment. Between 92% and 100% of students and women agreed that the
      program had clear learning objectives, was well organized, and was a useful and
      appropriate method of teaching that helped prepare them for the clinical setting.
      CONCLUSION: This pelvic examination educational program has been evaluated
      positively by students and participant women and has resulted in a significant
      improvement in the amount of pelvic examination experience that medical
      undergraduates obtain.

PMID- 15167846
TI  - Variation in medical student grading criteria: a survey of clerkships in
      obstetrics and gynecology.
AB  - OBJECTIVE: Our purpose was to assess how obstetrics/gynecology clerkships
      incorporate methods of student assessment into grades. STUDY DESIGN: A survey
      that included a broad range of assessment methods was distributed to
      obstetrics/gynecology clerkship directors registered with the Association of
      Professors of Gynecology and Obstetrics. Respondents were asked to indicate the
      methods used for assessment and to indicate the weight assigned to these methods
      in determining a student grade. RESULTS: Of the 146 surveys distributed, there
      were 53 respondents (36.4%). The most common methods of subjective assessment
      included evaluation of patient presentation skills and performance on ward
      rounds. The 2 most commonly used objective methods, general assessment of
      cognitive knowledge and the National Board of Medical Examiners Subject
      Examination in Obstetrics and Gynecology, generally accounted for 75% of the
      final grade, although these same 2 components also had the widest range of
      assigned weights reported. CONCLUSION: Assessment methods and incorporation into
      a final grade vary widely across obstetrics/gynecology clerkships.

PMID- 15167847
TI  - Feasibility of laparoscopic debulking with electrosurgical loop excision
      procedure and argon beam coagulator at recurrence in patients with previous
      laparotomy debulking.
AB  - OBJECTIVES: Our purpose is to assess the feasibility and success of laparoscopic
      ovarian debulking with electrosurgical loop excision procedure (LEEP) and argon
      beam coagulator (ABC). METHODS: Thirty-six consecutive asymptomatic patients with
      chemosensitive stage III or IV ovarian cancer who had undergone prior laparotomy
      debulking and chemotherapy, underwent laparoscopic debulking at the time of
      elevated CA 125. Preoperative abdominal/pelvic computed tomography was negative.
      Operative laparoscopy was performed through an open technique in the left upper
      quadrant. Tumors were debulked laparoscopically by using the LEEP and the ABC.
      RESULTS: Of 36 patients, 34 (94%) underwent successful laparoscopic debulking
      without requiring laparotomy. Of 34 patients, 32 (94%) had all visible disease
      resected at laparoscopy; 6% had surgical complications. Median time for surgery
      was 2.6 hours, median blood loss 70 mL, and median hospital stay 1 day. Seventy
      four percent had a complete response after laparoscopic debulking and
      chemotherapy with a median progression free survival of 1.1 years. CONCLUSION: We
      present the first report of laparoscopic ovarian debulking using LEEP and ABC
      after elevation of CA 125 in chemosensitive, asymptomatic patients who had
      undergone prior laparotomy debulking. Laparoscopic debulking appears feasible
      (94%), successful (94%), and safe (6% complications). Prospective randomized
      trials are needed to determine the optimal management of asymptomatic,
      chemosensitive patients with elevated CA 125.

PMID- 15167848
TI  - Morbidity of cytoreductive surgery in the elderly.
AB  - OBJECTIVES: While ovarian cancer is often seen in elderly patients, such women
      are often not treated as aggressively as younger patients. In this study, we
      evaluated the feasibility and morbidity of cytoreductive surgery in the elderly.
      STUDY DESIGN: A retrospective review was performed of all patients with
      epithelial ovarian carcinoma who underwent exploratory laparotomy. Patients were
      stratified by age into those younger than 70 years of age and those 70 years of
      age and older. RESULTS: A total of 175 patients, 129 (74%) in the younger cohort
      and 46 (26%) in the older cohort, were identified. Optimal cytoreduction to a
      largest tumor diameter of <1 cm was possible in 82% of the younger patients vs
      81% of the elderly (P =1.00). The stage distribution, complication rate, duration
      of hospital stay, and survival were similar between the groups. CONCLUSION:
      Aggressive surgical cytoreduction is both safe and feasible in elderly patients.
      Advanced age should not be considered a contraindication to cytoreductive
      surgery.

PMID- 15167849
TI  - Gynecological surgery in octogenarians and nonagenarians.
AB  - OBJECTIVE: The study analyzed morbidity and mortality rates among octogenarian
      and nonagenarian patients who underwent operations for gynecologic indications.
      STUDY DESIGN: A retrospective chart review was performed for patients, aged
      >or=80 years, who underwent gynecologic procedures between January 1, 1995, and
      September 30, 2000. Information obtained included a complete medical history,
      type of surgical procedure, length of hospital stay, and discharge disposition.
      Simple demographic statistics were used. RESULTS: Sixty-two patients (mean age,
      83.6 years) were identified. Seventy-seven operative procedures, 49 major and 28
      minor, were performed. All patients were discharged home, except 2, who were
      discharged to nursing homes. Sixteen patients, who underwent minor procedures,
      were discharged the same day, and 6 patients were admitted for "23" hour stays.
      There were 11 perioperative complications and no perioperative deaths.
      CONCLUSION: Successful gynecologic surgical outcomes with minimal morbidity are
      achievable in octogenarian patients and nonagenarian patients with optimization
      of co-medical conditions and careful perioperative treatment. Age should not be
      the sole determinant in the decision-making process.

PMID- 15167850
TI  - HOXA10 gene expression in human fallopian tube and ectopic pregnancy.
AB  - OBJECTIVE: The molecular mechanisms underlying ectopic implantation have not been
      well characterized. Here we investigate HOXA10 gene expression at the site of
      ectopic implantation as compared with the endometrium and with the normal
      fallopian tube. STUDY DESIGN: Northern blot analysis was used to evaluate HOXA10
      gene messenger RNA level in various segments of normal pregnant and nonpregnant
      human fallopian tube, ectopic pregnancy, and endometrium. RESULTS: Normal human
      fallopian tube expressed minimal levels of HOXA10 gene messenger RNA in the
      nonpregnant state. A trend toward a greater expression of HOXA10 gene was
      observed in the normal fallopian tube during pregnancy, but the difference was
      not statistically significant (P =.075). HOXA10 gene messenger RNA expression was
      up-regulated significantly at the site of implantation in ectopic pregnancy (P
      <.001), and its expression approached that of the endometrium during normal
      pregnancy (P =.33). CONCLUSION: HOXA10 gene expression is up-regulated at the
      ectopic implantation site in the fallopian tube, approaching that of the
      endometrium in normal intrauterine gestation. Inherently increased HOXA10 gene
      expression in the fallopian tube or dysregulation of HOXA10 gene expression by an
      abnormally implanting blastocyst may play a role in ectopic implantation.

PMID- 15167851
TI  - Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial
      neoplasia and cervical cancer.
AB  - OBJECTIVE: alpha-Tocopherol is a potent antioxidant that protects cell membranes
      against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane
      alpha-tocopherol concentrations, and altered levels may suggest membrane damage.
      The objective of this study was to determine the levels of alpha-tocopherol and
      alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and
      red blood cells that were obtained from control subjects and patients with
      cervical intraepithelial neoplasia and cervical cancer. STUDY DESIGN: In this
      cross-sectional study, 72 women, (32 African American and 40 Hispanic) were
      recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia;
      14 women had cervical cancer, and 21 women were considered control subjects, who
      had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl
      quinone levels were determined in red blood cell and plasma by high-pressure
      liquid chromatography. RESULTS: Plasma levels of alpha-tocopherol and alpha
      tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively,
      by Kruskal-Wallis test) in study groups compared with the control group; red
      blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not
      altered significantly. CONCLUSION: The lower alpha-tocopherol level that was
      observed in this study is consistent with our previous reports of decreased
      antioxidant concentrations and increased oxidative stress in women with cervical
      intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha
      tocopheryl quinone levels suggest undamaged cell membrane. Further studies are
      needed to investigate the potential role of oxidative stress in cervical
      intraepithelial neoplasia.

PMID- 15167852
TI  - Effect of topical bupivacaine on postoperative pain after laparoscopic tubal
      sterilization with Filshie clips.
AB  - OBJECTIVE: The purpose of this study was to evaluate postoperative pain after the
      administration of topical bupivacaine during laparoscopic sterilization with
      Filshie clips. STUDY DESIGN: Sixty-three women who underwent laparoscopic tubal
      sterilization with Filshie clips were assigned randomly to receive topical
      bupivacaine or placebo. Presence of pain, pain intensity, nausea, vomiting,
      timing of request for pain medication, and pain medication requirements were
      assessed postoperatively. RESULTS: Patient demographics were similar between the
      2 groups. Topical bupivacaine decreased the incidence (P=.005) and intensity
      (P=.028) of postoperative pain at 30 minutes. No differences in incidence or
      severity of pain were seen at hospital discharge or on postoperative day 1.
      CONCLUSION: Topical bupivacaine that is applied to the fallopian tubes at the
      time of laparoscopic tubal sterilization with the Filshie clip decreases
      immediate postoperative pain.

PMID- 15167853
TI  - Abdominopelvic inspection during nonemergent laparoscopic procedures: who looks?
AB  - OBJECTIVE: A study was performed to determine whether surgeons and gynecologists
      inspect the entire abdomen/pelvis at the time of nonemergent laparoscopic
      surgery. STUDY DESIGN: A retrospective chart audit was conducted of patients who
      underwent elective laparoscopic cholecystectomy or laparoscopic tubal ligation.
      Dictated and hand-written operative notes were reviewed. Any documentation of the
      pelvic structures from cholecystectomy operative notes or the upper abdomen from
      tubal ligation operative notes was determined to be positive for abdominopelvic
      surveillance. RESULTS: A total of 771 operative notes were reviewed, which
      included 358 tubal ligations and 413 laparoscopic cholecystectomies. Two hundred
      four of 358 (57%) tubal ligations performed by gynecologists had a survey of the
      upper abdomen versus 36 of 413 (8.7%) cholecystectomies performed by surgeons
      that had a survey of the pelvis. CONCLUSION: Gynecologists and general surgeons
      either do not document or do not perform total abdominopelvic inspection
      universally.

PMID- 15167854
TI  - Sexual functioning and patient expectations of sexual functioning after
      hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to assess sexual functioning and patient
      expectations of sexual functioning after hysterectomy. STUDY DESIGN: Seventy-five
      patients who had undergone hysterectomy at an urban academic medical center were
      surveyed about sexual function at the time of hysterectomy and after
      hysterectomy. Chi-squared tests compared responses for discrete outcomes. RESULT:
      Most patients expected no change in sexual desire or orgasm quality. Hysterectomy
      had no effect on the frequency of sexual activity or on orgasmic response.
      Postoperatively, patients were less likely to report pain with intercourse
      (relative risk, 5.34; 95% CI, 2.2-12.95; P =.00002): 49.3% of patients had
      discussed sexual functioning after hysterectomy with their physicians, and 64.8%
      of patients recalled initiating the discussion. CONCLUSION: Most patients
      expected and experienced no change in sexual desire, orgasm frequency, or orgasm
      intensity. Hysterectomy appears to result in decreased pain with sexual
      relations.

PMID- 15167855
TI  - Leukemia inhibitory factor and homeobox a10 gene expression in an ectopic
      pregnancy model for implantation.
AB  - OBJECTIVE: We investigated the expression of leukemia inhibitory factor and
      homeobox a10 in endometrium that was derived from patients with concurrent
      ectopic pregnancies compared with nonpregnant luteal phase endometrium from the
      same patients. STUDY DESIGN: Endometrial biopsy specimens that were obtained from
      women (n=3) who underwent surgery for ectopic pregnancy were matched with biopsy
      specimens in a nonpregnant luteal phase from the same patients. Quantitative
      reverse transcription polymerase chain reaction for leukemia inhibitory factor
      and homeobox a10 was performed. Polymerase chain reaction products were assayed
      with laser detection of nanogram quantities of complementary deoxyribonucleic
      acid. Ratios of each implantation marker to glyceraldehyde-3-phosphate
      dehydrogenase as an internal standard were compared for quantification. RESULTS:
      Leukemia inhibitory factor expression is increased in endometrium from ectopic
      pregnancy; homeobox a10 is increased in luteal phase endometrium. CONCLUSION:
      Leukemia inhibitory factor appears to be regulated by human chorionic
      gonadotropin or other factors of pregnancy; homeobox a10 is regulated by ovarian
      steroids of the luteal phase.

PMID- 15167856
TI  - Digital rectal fecal occult blood screening during gynecologic examination.
AB  - OBJECTIVE: The purpose of this study was to test the feasibility of digital
      rectal fecal occult blood screening during pelvic examination. STUDY DESIGN: We
      reviewed the data for 232 consecutive women who underwent digital rectal fecal
      occult blood screening during routine pelvic examination and who had had at least
      1-year of follow-up visits: 59% of the women were followed for gynecologic
      cancer, and 41% of the women were followed for benign gynecologic disease. The
      median age was 62 years. Patients with positive digital rectal fecal occult blood
      screening were sent for gastroenterologic examination. RESULTS: Sixteen of 232
      patients (7%) had a positive digital rectal fecal occult blood screening result.
      On gastroenterologic examination, 5 of the 16 patients (31%) were found to have
      disease (2 polyps, 1 diverticular disease, 2 radiation proctitis). At 1-year
      follow-up, no patient had colon cancer. CONCLUSION: Until better compliance can
      be obtained with home stool sample fecal occult blood testing, we recommend a
      larger study of digital rectal fecal occult blood screening during gynecologic
      examination to verify our results.

PMID- 15167857
TI  - Treatment of high-grade squamous intraepithelial lesions: a 2- versus 3-step
      approach.
AB  - OBJECTIVE: The purpose of this study was to determine whether colposcopically
      directed biopsy is a necessary step in the evaluation of patients with high-grade
      squamous intraepithelial lesions. STUDY DESIGN: A retrospective analysis was
      conducted of the correlation between the high-grade squamous intraepithelial
      lesion Papanicolaou test and the colposcopically directed biopsy and the
      correlation between the high-grade squamous intraepithelial lesion Papanicolaou
      test and the loop electrosurgical excisional procedure. RESULTS: Of 72 patients
      with high-grade squamous intraepithelial lesions on Papanicolaou test, 48
      patients had a pathologic diagnosis on cervical biopsy of CIN II or greater,
      which provides a 67% correlation between the Papanicolaou test and the
      colposcopically directed biopsy. Fifty-six patients had a pathologic diagnosis on
      loop electrosurgical excisional procedure of CIN II or greater, which provides a
      78% correlation between the Papanicolaou test and the loop electrosurgical
      excisional procedure. The median interval between the Papanicolaou test and the
      definitive treatment was significantly longer (P <.001) when colposcopically
      directed biopsy was performed before the loop electrosurgical excisional
      procedure. CONCLUSION: The colposcopically directed loop electrosurgical
      excisional procedure after a high-grade squamous intraepithelial lesion
      Papanicolaou test may reduce the time interval between diagnosis and treatment;
      furthermore, it offers equal correlation when compared with traditional
      treatment.

PMID- 15167859
TI  - Other primary malignancies in patients with uterine corpus malignancy.
AB  - OBJECTIVE: The purpose of this study was to determine the occurrence of multiple
      primary malignancies in patients with uterine corpus malignancy. STUDY DESIGN: We
      conducted a tumor registry search and a medical record review. RESULTS: Uterine
      corpus malignancy was reported in 1505 of 25605 women (6%) in the registries, of
      which 131 of 1505 women (9%) had multiple primary malignancies. Patients with
      uterine corpus malignancy with multiple primary malignancies were more likely to
      have had primary malignancies of the ovary (relative risk, 10; 95% CI, 6.2-17)
      and colon (relative risk, 2; 95% CI, 1.0-4.3) and less likely to have had primary
      malignancies of the cervix (relative risk, 0.4; 95% CI, 0.17-0.97) compared with
      women who had only one primary malignancy. A family history of malignancy was
      reported in only 44% of the patients with uterine corpus malignancy with multiple
      primary malignancies and 32% of those patients whose multiple primary
      malignancies were from the ovary or colon. CONCLUSION: The development of
      multiple primary malignancies in patients with uterine corpus malignancy may
      indicate an inherited predisposition, especially in those patients whose multiple
      primary malignancies include the ovary or colon. That predisposition may not be
      detected by routine family history.

PMID- 15167858
TI  - Sexual response in the patient after hysterectomy: total abdominal versus
      supracervical versus vaginal procedure.
AB  - OBJECTIVE: The present study examines the patient's own appraisal of her sexual
      responsiveness after hysterectomy. STUDY DESIGN: Four hundred women who had
      undergone hysterectomy within a 3-year period were selected randomly and asked to
      respond to a questionnaire that was devised to ascertain the patient's own
      objective evaluation of self-image, sexuality, and sexual response before and
      after hysterectomy. The confidential responses were analyzed, noting the presence
      of any significant divergence between demographic and procedural cohorts.
      RESULTS: Of 126 respondents, 48.4% underwent total abdominal hysterectomy; 34.1%
      underwent vaginal hysterectomy, and 17.4% underwent supracervical hysterectomy.
      The mean patient age was 49.7+/-8.7 years. No direct correlation was found
      between hysterectomy type and age. Most women did not report any significant
      deterioration in mental attitude after the procedure (P =.788). Self and body
      image also remained consistent, with only 25.3% indicating a change for the
      worse. Only 10.3% of respondents felt less feminine after hysterectomy; nearly
      70% of the respondents did not feel less feminine. Responses that pertained to
      libido, sexual activity, or feelings of femininity did not reveal significant
      changes (P >.05). Satisfaction with procedural choice was positive (54.8%), with
      only 7.1% responding unfavorably. CONCLUSION: The responses suggest that neither
      self-image nor sexuality need diminish after hysterectomy. The type of
      hysterectomy that was performed did not appear to affect the attitudes of the
      respondents.

PMID- 15167861
TI  - Differences in symptoms between patients with benign and malignant ovarian
      neoplasms.
AB  - OBJECTIVE: The purpose of this study was to determine the symptoms that are
      experienced by patients who receive a diagnosis of early ovarian cancer and to
      compare those symptoms with the symptoms that are experienced by patients with
      late ovarian cancer, borderline ovarian cancer, and benign ovarian neoplasms.
      STUDY DESIGN: This study used a retrospective case-control design. Cases of
      invasive and borderline ovarian cancer (n=147 patients) were compared with 76
      patients with benign ovarian neoplasms. RESULTS: Patients with early ovarian
      cancer were significantly more likely to have symptoms of mass effect (urinary
      frequency, constipation, palpable mass, pelvic pressure) compared with patients
      with benign ovarian neoplasms (67% vs 15%; P <.001), late stage disease (67% vs
      40%; P =.008), and borderline cancer (67% vs 33%; P =.007). CONCLUSION: Mass
      effect symptoms were the only symptoms that differentiated patients with early
      stage ovarian cancer from all other groups of patients. However, one third of the
      patients with early ovarian cancer did not report any of these symptoms.

PMID- 15167860
TI  - Coenzyme Q10 and lipid-related gene induction in HeLa cells.
AB  - OBJECTIVE: Coenzyme Q10 is an antioxidant that may have a therapeutic role in
      cervical cancer. STUDY DESIGN: We investigated the cellular and molecular effects
      of 30 micromol/L Coenzyme Q10 in HeLa cells. Cell growth assays, fluorescence
      activated cell sorting analyses, and Oil Red O staining were performed.
      Microarray experiments were performed in duplicate and analyzed on the basis of 2
      fold changes in levels of gene expression. RESULTS: Coenzyme Q10 inhibited cell
      growth and led to apoptosis. Microarray analysis showed that 264 sequences were
      altered over time, with enrichment in lipid-related genes. Enhanced lipid
      accumulation was confirmed with Oil Red O staining. CONCLUSION: A lipid response
      to Coenzyme Q10 may affect mechanisms of growth inhibition in HeLa cells.

PMID- 15167863
TI  - Emergency peripartum hysterectomy: a comparison of cesarean and postpartum
      hysterectomy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the incidence, risk
      factors, indications, outcomes, and complications of emergency hysterectomy
      performed after cesarean deliveries (cesarean hysterectomy) and vaginal
      deliveries (postpartum hysterectomy). STUDY DESIGN: We conducted a retrospective
      cohort study from 1990 to 2002 of patients who had peripartum hysterectomies at a
      single tertiary hospital. Comparisons were made between cesarean and postpartum
      hysterectomies. RESULTS: There were 55 cases of emergency peripartum hysterectomy
      (38 cesarean hysterectomies, and 17 postpartum hysterectomies), for a rate of 0.8
      per 1000 deliveries. Overall, the most common indication for hysterectomy was
      uterine atony (56.4%), followed by placenta accreta (20.0%). Average estimated
      blood loss was 3325.6+/-1839.2 mL, average operating time was 157.1+/-75.4
      minutes, average time from delivery to completing the hysterectomy was 333.8+/
      275.7 minutes, and the average length of hospitalization was 11.0+/-7.9 days. The
      cesarean delivery rate at Grady Memorial Hospital during the study period was
      14.2%. There were no statistically significant differences between variables
      examined when comparisons were made by cesarean vs postpartum hysterectomy.
      CONCLUSION: Uterine atony is the leading indication for emergency hysterectomy
      performed following cesarean and vaginal deliveries.

PMID- 15167862
TI  - Glyburide for the treatment of gestational diabetes.
AB  - OBJECTIVE: This study was undertaken to evaluate the effectiveness of glyburide
      in patients with gestational diabetes who failed diet therapy. METHODS: Patients
      who were beyond the first trimester and who failed to achieve satisfactory
      glucose control with diet therapy were treated with glyburide, at a starting dose
      of 2.5 mg daily. The dose was increased in increments to a maximum of 20 mg/day.
      The main treatment outcome was achievement of satisfactory glucose control,
      defined as a mean plasma fasting glucose 90 mg % or less and mean 1-hour
      postprandial plasma glucose determinations 135 mg % or less. Patients who failed
      to achieve satisfactory control were treated with twice-daily doses of insulin.
      RESULTS: During the period July 2001 through December 2002, we managed 197
      patients with gestational diabetes. One-hundred twenty-four patients responded to
      diet alone; 73 were treated with glyburide. Of the 73 patients, 59 (81%, 95% CI
      76.4-85.6) achieved satisfactory glucose control with glyburide; 44 women
      required 7.5 mg/day or less. Eleven of the 59 women (19%) had macrosomic infants.
      Eight patients (11%) experienced noticeable side effects related to glyburide;
      only 1 patient discontinued treatment. CONCLUSION: Approximately 80% of patients
      with gestational diabetes who fail to respond to diet therapy can be treated
      effectively with glyburide.

PMID- 15167864
TI  - Misoprostol for uterine evacuation in patients with early pregnancy failures.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      misoprostol that is administered intravaginally for uterine evacuation in
      patients with early pregnancy failures. STUDY DESIGN: From March 2001 through
      March 2003, we treated 41 patients who had early pregnancy failures with vaginal
      misoprostol, 800 microg. A second course of misoprostol was administered if
      uterine evacuation did not occur in 24 hours. Patients who had no response to
      misoprostol underwent a surgical curettage. Our principal outcome measures were
      the percentage of patients who had successful evacuation of the products of
      conception and the frequency of adverse drug effects. RESULTS: Twenty-six
      patients had successful uterine evacuation with a single course of misoprostol; 6
      patients required a second course. The overall success rate was 78% (95% CI, 63,
      88). No patient experienced a serious adverse drug effect. CONCLUSION:
      Intravaginal misoprostol is a safe, effective alternative to surgical curettage
      for the treatment of early pregnancy failure.

PMID- 15167865
TI  - Is hypotonic dysfunctional labor associated with hypophosphatemia?
AB  - OBJECTIVE: The purpose of this study was to determine whether hypotonic
      dysfunctional labor is associated with hypophosphatemia. STUDY DESIGN: We
      conducted a prospective nested case control study of term women who were in
      active labor. Serum phosphate samples were drawn at admission with active labor
      and before delivery. Phosphate concentration was compared between control
      subjects and women with hypotonic, dysfunctional uterine contractions. RESULTS:
      Both serum samples were available for 90 women. Hypophosphatemia was documented
      in 14% of the participants. There was no significant difference in phosphate
      concentration between the 2 groups either at admission or before delivery. The
      mean decrease in phosphate concentration between admission and delivery was
      similar between the 2 cohorts. CONCLUSION: Although transient hypophosphatemia is
      found commonly in laboring women, hypotonic dysfunctional contractions are not
      associated with mild hypophosphatemia.

PMID- 15167866
TI  - Effect of glutamine on preimplantation mouse embryo development in vitro.
AB  - OBJECTIVES: The purpose of this research was to study the independent effect of
      the amino acid glutamine on preimplantation mouse embryo development in vitro.
      STUDY DESIGN: Two-cell stage mouse embryos were cultured in human tubal fluid
      medium in the presence and absence of 1 mmol/L of glutamine. Outcomes for
      morphology and cleavage rates were compared with Fisher's and Mann-Whitney's
      tests, respectively. RESULTS: Glutamine increased the proportion of embryos that
      developed to the blastocyst stage (86.4%) compared with those cultured without
      glutamine (59.1%) (P =.052). The percentages of embryos developing to the morula
      or hatching blastocyst stages were comparable in the 2 groups. Blastocyst total
      cell numbers were significantly higher in the glutamine group (34+/-1.7 vs 18.5+/
      3.5, respectively; values are mean+/-SEM, P =.044). CONCLUSION: The amino acid
      glutamine independently improves preimplantation mouse embryo development in
      vitro. Further studies are needed to examine the applicability of these results
      to humans.

PMID- 15167867
TI  - Factors influencing maternal perception of uterine contractions.
AB  - OBJECTIVES: The purpose of this study was to assess factors associated with
      perception of uterine contractions. STUDY DESIGN: A database of ambulatory
      uterine activity monitoring was examined. All patients having singleton
      pregnancies evaluated between March 1997 and March 2002 were eligible for
      analysis. Data were divided into 4 groups by maternal prepregnancy body mass
      index (BMI): lean (<20 kg/m(2)), normal (>or=20 to <25 kg/m(2)), overweight
      (>or=25 to <30 kg/m(2)), and obese (>or=30 kg/m(2)). The percentage of
      contractions perceived during observation was compared between groups. Variables
      interrogated included maternal weight and parity. Statistical analysis included t
      test, analysis of variance (ANOVA), and linear regression. RESULTS: Data from
      7808 patients (556,382 hr) were analyzed. A significant reduction in perception
      of contractions occurred with increasing BMI between each classification, P
      <.001. A significant reduction in perception of contractions was also noted
      between nulliparous and multiparous patients at each weight classification, P
      <.001. CONCLUSION: Obese, nulliparous patients have the greatest difficulty
      perceiving contractions. Such data may help explain unattended birth or late
      presentation for care in this group.

PMID- 15167868
TI  - Updating reference values for placental weights in Northern Alberta.
AB  - OBJECTIVE: The purpose of this study was to establish normal parameters for
      placental weights and fetal/placental weight ratios. STUDY DESIGN: Placentas
      (2402) from uncomplicated singleton deliveries at the Royal Alexandra Hospital
      (Edmonton, Alberta) were collected from 1997 to 1998 and weighed after fixation.
      The nonparametric Mann-Whitney test was applied. RESULTS: New reference values
      were developed for fixed placental weights. Placentas at the 90th percentile were
      50 to 100 g heavier than previously reported. Fetal/placental weight ratios at
      term were similar to published values. CONCLUSION: The new placental weight
      reference values from our institution represent a recent and local population.
      New values may partly reflect parallel increases in term birth weights.

PMID- 15167869
TI  - The incidences of positive Kleihauer-Betke test in low-risk pregnancies and
      maternal trauma patients.
AB  - OBJECTIVE: This study was undertaken to determine the incidence of positive
      Kleihauer-Betke (KB) tests in low-risk, third trimester patients and compare them
      with historical "control" patients who received KB tests for maternal trauma
      evaluations. STUDY DESIGN: Institution Review Board approval was obtained. KB
      tests were performed on 100 low-risk gravid women at the time of their routine
      glucose challenge tests after informed consent. All specimens were analyzed for
      fetal hemoglobin using the Clayton modification. Patients with identified risk
      factors for placental abruption were excluded. A retrospective chart review was
      performed on 583 historical control patients from 1998 to 2001 who had undergone
      maternal trauma evaluations, of which 151 had a KB test at comparable gestations.
      Demographic data from medical records were reviewed and compared. Data were
      analyzed with 2-sided Student t test, Mann-Whitney rank sum, and chi(2) tests, as
      indicated. RESULTS: Of the low-risk women 5 of 98 (5.1%) had a positive KB test,
      whereas 4 of 151 (2.6%) trauma patients had a positive test (P=.31). None of
      these positive results were associated with a clinical abruption or fetal
      distress. One low-risk patient with sickle cell trait had a 40 mL KB result.
      CONCLUSION: The incidence of a positive KB test in low-risk pregnancies does not
      differ from maternal trauma patients. Therefore, the presence of a positive KB
      test alone does not necessarily indicate pathologic fetal-maternal hemorrhage in
      patients with trauma.

PMID- 15167870
TI  - Delayed postpartum preeclampsia: an experience of 151 cases.
AB  - OBJECTIVE: Preeclampsia affects 6% to 8% of pregnancies. There are few data
      regarding hypertensive disorders that are diagnosed in the postpartum period. Our
      purpose was to determine the demographics, outcomes, and treatment of this
      complication. STUDY DESIGN: This was a multicenter retrospective study of women
      who had received a diagnosis of hypertension/preeclampsia in the postpartum
      period. Inclusion criteria were readmission of a patient with this diagnosis
      (<or=6 weeks after the delivery). RESULTS: Data from 151 women were studied.
      Complications included 24 cases (15.9%) of eclampsia, 9 cases (5.9%) of pulmonary
      edema, 6 cases (3.9%) of endomyometritis, 2 cases (1.3%) of thromboembolism, and
      1 case of maternal death. Seventy-eight patients required antihypertensive
      medications on discharge. Subanalysis performed between the eclamptic and non
      eclamptic women showed no difference among groups. CONCLUSION: Delivery does not
      eliminate the risk for preeclampsia and its complications. Efforts should be
      directed at the continued monitoring, reporting, and evaluating of the symptoms
      of preeclampsia during the postpartum period.

PMID- 15167871
TI  - Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the
      use of radiation.
AB  - BACKGROUND: Biliary disease in pregnancy is a relatively uncommon condition; the
      diagnosis of this condition is not standardized. Furthermore, the use of
      radiographic imaging studies and therapeutic approaches in pregnancy is limited
      because of the possibility of fetal exposure. STUDY DESIGN: During a 2-year
      interval of 2001 to 2002, we successfully performed endoscopic retrograde
      cholangiopancreatography (ERCP) studies in 6 pregnant women between 6 and 30
      weeks of gestation with symptomatic acute cholangitis or pancreatitis without
      irradiation exposure or major maternal complications. Five of the women had
      classic symptoms of severe right upper quadrant abdominal pain, gallbladder
      stones, jaundice, and dilated bile ducts on ultrasonic evaluation. One woman had
      severe recurrent pancreatitis during early pregnancy 4 years after a
      cholecystectomy. The cases are compiled to provide a descriptive review of ERCP
      without the use of radiation imaging treatment for these conditions. RESULTS:
      Maternal outcome: After ERCP, jaundice resolved in all cases. No further episodes
      of pancreatitis occurred during the 1 affected pregnancy. No post-ERCP
      complications occurred during this series. Two patients required cholecystectomy
      later, one in the postpartum period and the other 5 weeks post-ERCP. Fetal
      outcome: Two infants were born at term without complications. Two infants were
      born prematurely at 35 weeks, 1 with significant growth retardation and pulmonary
      complications and 1 without developmental problems or complications. Two mothers
      were lost to follow-up; the outcomes of their pregnancies are unknown.
      CONCLUSION: The use of ERCP in pregnancy is limited because of the undesirable
      effects of radiation exposure to the fetus.

PMID- 15167872
TI  - Effect of halogen light stimulation on nonstress testing.
AB  - OBJECTIVE: This study was undertaken to determine whether external stimulation
      using a halogen light source influences fetal heart rate (FHR) responsiveness and
      nonstress test results. STUDY DESIGN: A total of 107 patients at 32 to 42 weeks'
      gestation undergoing a nonstress test were randomly assigned to have either
      transabdominal light stimulation or no light stimulation. The light (Vector
      Compact Sport Spot, Ft Lauderdale, Fla) was turned on for 10 seconds. If no
      qualifying FHR acceleration was observed, then the stimulus was repeated at 10
      minute intervals for a maximum of 3 times. The investigators were blinded as to
      light stimulation for FHR interpretation. RESULTS: Reactive results were present
      in 52 cases in each group. Light stimulation led to a significantly shorter time
      (P <.02) until the first FHR acceleration (difference: 2.1 minutes; 95% CI 0.4
      3.8 minutes). The height and width of the first acceleration were
      indistinguishable between groups. The time until a reactive result was
      significantly shorter after light stimulation (difference: 4.2 minutes; 95% CI
      2.0-6.4 minutes). CONCLUSION: The earlier onset of FHR accelerations after
      halogen light stimulation prompted a more rapid reactive nonstress test result.

PMID- 15167873
TI  - Are elevated fetal nucleated red blood cell counts an indirect reflection of
      enhanced erythropoietin activity?
AB  - OBJECTIVE: Animal and human studies demonstrated elevated erythropoietin (EPO)
      levels in response to intrauterine hypoxic events. Other studies documented an
      association between fetal hypoxia and elevated nucleated red blood cell (NRBC)
      counts and have speculated that it is the elevation of EPO that results in an
      increase in NRBC counts. Thus, the purpose of our study was to determine the
      correlation between EPO levels and NRBC counts in the human fetus. STUDY DESIGN:
      Data were collected prospectively between April and July of 2003. Term singleton
      pregnancies were eligible to participate in the study. Umbilical cord blood was
      collected immediately after birth for determination of fetal EPO levels and NRBC
      counts. RESULTS: Forty pregnancies formed the study population. The mean
      gestational age at delivery was 39.5 +/- 1.2 weeks (+/-SD) and the mean birth
      weight was 3500 +/- 372 g. The median EPO (mU/mL) was 34 (range 13-427). The
      median NRBC/100 white blood cells was 10 (range 0-150). A simple regression
      analysis indicated that NRBC counts are significantly and positively correlated
      with EPO (P=.0004, R(2)=0.287). CONCLUSION: Our results suggest a significant
      association between EPO and NRBC counts in term singleton fetuses. These results
      support the hypothesis that fetal NRBC and EPO are interrelated. However, the
      relatively low R(2) indicates that there are other (yet to be determined) hypoxia
      derived mediators that result in an elevation of fetal NRBC counts.

PMID- 15167874
TI  - Risk of uterine rupture in labor induction of patients with prior cesarean
      section: an inner city hospital experience.
AB  - OBJECTIVE: This study was undertaken to determine the risk of uterine rupture in
      patients induced with oxytocin or misoprostol after 1 or more previous cesarean
      sections. STUDY DESIGN: Patients with 1 or more previous cesarean sections who
      delivered after 28 weeks' gestation between 1996 and 2002 were identified by
      database. Among 3533 total patients, rates of uterine rupture were compared among
      4 groups: oxytocin induction (n = 430), misoprostol induction (n = 142),
      spontaneous labor (n = 2523), and repeat cesarean section without labor (n =
      438). Statistical analysis included chi(2) test, Fisher exact test, unpaired t
      test, and Mantel-Haenszel test. RESULTS: Rate of rupture was increased in all
      inductions compared with that of the spontaneous labor group. Among patients with
      1 prior cesarean, rupture rates with misoprostol and oxytocin induction were 0.8%
      and 1.1%, respectively. CONCLUSION: Induction of labor with oxytocin or
      misoprostol is associated with a higher rate of uterine rupture compared with
      those who deliver after spontaneous labor. After 1 prior cesarean, rupture rate
      with misoprostol induction is not increased compared with oxytocin induction.

PMID- 15167875
TI  - The timing of elective delivery in preterm premature rupture of the membranes: a
      survey of members of the Society of Maternal-Fetal Medicine.
AB  - OBJECTIVE: We sought to assess the gestational age at which elective delivery is
      considered in an otherwise uncomplicated patient with preterm premature rupture
      of the membranes (PROM) by members of the Society of Maternal Fetal-Medicine
      (SMFM). STUDY DESIGN: A 3-page survey was mailed to members of the SMFM for this
      observational study. Information solicited included demographic data and practice
      patterns for the timing of delivery in patients with preterm PROM. RESULTS: Seven
      hundred seventeen questionnaires (40%) were completed. The majority (81%) did not
      believe there is a consensus regarding the gestational age for elective delivery
      in patients with preterm PROM. With confirmed fetal lung maturity, the greatest
      number of respondents selected 32 and 34 weeks as the earliest gestational age
      for elective delivery. In the absence of fetal pulmonary maturity testing, the
      majority of respondents chose 34 weeks. CONCLUSION: Most SMFM respondents
      electively deliver uncomplicated patients with preterm PROM by 34 weeks'
      gestation.

PMID- 15167876
TI  - Resident physician attire: does it make a difference to our patients?
AB  - OBJECTIVES: This study was performed to examine the preferences of patients
      regarding physician attire, and if their perception of physician competence was
      influenced by the physicians' clothing style. METHODS: Patients attending the
      obstetrics and gynecology clinic in which residents provided the majority of
      direct patient care were invited to participate in this study by completing a
      questionnaire. Patients were first asked to respond to 3 questions about their
      preference regarding physician attire. They were then asked to examine a series
      of photographs illustrating a variety of physician clothing styles worn by a
      model. Patients were asked to respond to 2 questions: 1). If your doctor is
      dressed in this outfit, would that make you more or less comfortable talking to
      your physician?, and 2). If your doctor is dressed in this outfit, would it make
      you feel more or less confident in his/her abilities? RESULTS: The majority of
      the respondents expressed no preference for their physician wearing a white coat
      (60%/110/183), or they did not respond that a physician's dress influenced their
      comfort level (63%/111/179) or the confidence (62%/114/181) they had in their
      physician. However, for both male and female physician models, the comfort level
      of patients and their perceptions of physician competence were the highest in
      response to images of physicians dressed in scrubs with a white coat, and least
      for casual dress. CONCLUSION: Resident physician attire makes a difference to
      patients. Our patients prefer the white coat with surgical scrubs. Casual
      clothing is less well liked by our patients.

PMID- 15167877
TI  - The known and the unknown about oxygen use.

PMID- 15167878
TI  - The "emergent circumstances" exception to the need for consent: the Texas Supreme
      Court ruling in Miller v. HCA.

PMID- 15167879
TI  - Actinomyces species and cerclage placement in neonatal sepsis: a case report.
AB  - A 26-year-old female with a history of preterm labor and cerclage placement
      presented at 29 weeks gestation. Twin girls were delivered at 2917 weeks. Twin A
      presented with clinical sepsis at birth. Twin A's blood cultures became positive
      for Actinomyces species on day of life 15. Despite aggressive medical management
      twin A died at 35 days of life.

PMID- 15167881
TI  - Neonatal seizures following lidocaine administration for elective circumcision.
AB  - We report a case of a 25-day old, former 34-week gestation male newborn who
      experienced neonatal seizures following administration of subcutaneous lidocaine
      for regional anesthesia during an elective circumcision prior to discharge.

PMID- 15167880
TI  - Transient neonatal jitteriness due to maternal use of sertraline (Zoloft).
AB  - We describe the occurrence of marked jitteriness and an enhanced startle response
      in a term infant after being exposed to sertraline in utero. An umbilical cord
      blood sample taken at the time of birth showed a sertraline concentration (<10
      ng/mL) below the reference range. On the third day during the peak of the
      symptoms, sertraline plasma concentration was <10 ng/mL, while his serotonin
      level (6 ng/mL) was below the reference range. The neurologic symptoms resolved
      by the fifth day. To date, there are no reports of transient neonatal jitteriness
      with maternal use of sertraline documented with low cord and neonatal plasma
      samples consistent with withdrawal syndrome.

PMID- 15167882
TI  - Amiodarone-induced neonatal hypothyroidism: a unique form of transient early
      onset hypothyroidism.
AB  - Amiodarone is an iodine-rich drug used to treat cardiac dysrhythmias. The
      structure of amiodarone resembles that of thyroxine, and treatment with
      amiodarone may alter thyroid function. The effects of antenatal amiodarone use on
      fetal/neonatal thyroid function have only been addressed in a limited number of
      patient reports. We describe two cases of transient neonatal hypothyroidism due
      to in utero amiodarone exposure, followed by a brief review of the available
      literature.

PMID- 15167885
TI  - Aggressive early total parental nutrition in low-birth-weight infants.
AB  - OBJECTIVE: This study aimed to compare nitrogen balance and biochemical tolerance
      of early aggressive versus late total parenteral nutrition in very-low-birth
      weight (VLBW) infants over the first week of life. STUDY DESIGN: In all, 32
      ventilator-dependent preterm infants were prospectively randomized into two
      groups. The Early Total Parenteral Nutrition (ETPN) group received 3.5 g/kilo-day
      amino acids (AA), and 3 g/kilo-day of 20% Intralipid (IL), starting within 1 hour
      after birth. The Late Total Parenteral Nutrition group (LTPN), started on a
      solution containing glucose during the first 48 hours of life, followed by 2
      g/kilo-day of AA and 0.5 g/kilo-day of IL. For the LTPN group AA and IL were each
      increased by 0.5 g/kilo-day to a maximum of 3.5 and 3 g/kilo-day, respectively.
      RESULTS: Nitrogen retention was significantly greater in all infants in the ETPN
      group throughout the 7-day study period. All infants in the LTPN group were in
      negative nitrogen balance during the first 48 hours of life, while those in the
      ETPN group were in positive nitrogen balance throughout. The mean (+/-SD)
      nitrogen retention in the ETPN was 384.5 mg/kilo-day (+/-20.2), compared to 203.4
      mg/kilo-day (+/-20.9) in the LTPN group (p <0.001). In each of the first 5 days
      of life, energy intake was significantly greater in the ETPN group compared to
      the LTPN group (p <0.001). Mean fluid intake during the study period was similar
      between, the ETPN and the LTPN groups (162 and 165 cm3/kilo-day, respectively).
      The mean weight gain was similar in the ETPN and LTPN groups. Plasma levels of
      cholesterol, triglycerides, bicarbonate, blood urea nitrogen, creatinine, and pH
      were similar in both groups during the study period. Mean (+/-SD) serum glucose
      in the LTPN group was higher, but remained in normal range (101.1+/-5.2 and
      80.8+/-5.4 mg/kilo-day, respectively). The mean peak serum bilirubin was
      significantly higher in the ETPN group, compared to The LTPN group (7.7 and 6.2
      mg/dl). CONCLUSION: This study shows that aggressive intake of AA and IL can be
      tolerated immediately after birth by VLBW infants. Also, ETPN significantly
      increased positive nitrogen balance and caloric intake, without increasing the
      risk of metabolic acidosis, hypercholesterolemia, or hypertriglyceridemia.

PMID- 15167886
TI  - Sudden infant death syndrome among twin births: United States, 1995-1998.
AB  - OBJECTIVES: To compare the incidence and risk factors for sudden infant death
      syndrome (SIDS) in twin and singleton births and to estimate the concordance of
      SIDS in twins. STUDY DESIGN: A cohort analysis using the National Center for
      Health Statistics Linked Birth and Infant Death files (1995-1998). RESULTS: Twins
      had higher SIDS rate (1.3/1000 live births) compared to singletons (0.7/1000 live
      births), relative risk: 1.9, 95% confidence interval: 1.68, 2.01. Male and small-
      for-gestational age infants as well as infants of black, unmarried, and smoking
      mothers were at increased risk for SIDS in both twins and singletons. Placental
      abnormalities also were associated with SIDS in singletons and twins, although
      this association failed to achieve statistical significance in twins. There is a
      higher rate of SIDS in the second twin after a first twin SIDS. CONCLUSIONS:
      Twins are at higher risk of SIDS than are singletons. Overall, the epidemiology
      of SIDS in twins is quite similar to that seen in singletons.

PMID- 15167887
TI  - A genomic screen identifies Dsk2p and Rad23p as essential components of ER
      associated degradation.
AB  - We developed a growth test to screen for yeast mutants defective in endoplasmic
      reticulum (ER) quality control and associated protein degradation (ERAD) using
      the membrane protein CTL*, a chimeric derivative of the classical ER degradation
      substrate CPY*. In a genomic screen of approximately 5,000 viable yeast deletion
      mutants, we identified genes necessary for ER quality control and degradation.
      Among the new gene products, we identified Dsk2p and Rad23p. We show that these
      two proteins are probably delivery factors for ubiquitinated ER substrates to the
      proteasome, following their removal from the membrane via the Cdc48-Ufd1-Npl4p
      complex. In contrast to the ERAD substrate CTG*, proteasomal degradation of a
      cytosolic CPY*-GFP fusion is not dependent on Dsk2p and Rad23p, indicating
      pathway specificity for both proteins. We propose that, in certain degradation
      pathways, Dsk2p, Rad23p and the trimeric Cdc48 complex function together in the
      delivery of ubiquitinated proteins to the proteasome, avoiding malfolded protein
      aggregates in the cytoplasm.

PMID- 15167888
TI  - Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated
      region.
AB  - The aspartyl protease BACE1 has a pivotal role in the pathogenesis of Alzheimer's
      disease. Recently, it was shown that in Alzheimer's disease patients, BACE1
      levels were elevated although mRNA levels were not changed compared with
      controls. Here, we demonstrate that the 5'-untranslated region (5'UTR) of BACE1
      controls the rate of BACE1 translation. In the presence of the 5'UTR, we observed
      more than 90% reduction of BACE1 protein levels in HEK293, COS7 and H4 cells, and
      a similar reduction of BACE1 activity in vitro. mRNA levels were not affected,
      demonstrating that the 5'UTR repressed the translation but not the transcription
      of BACE1. The 3'UTR did not affect BACE1 expression. An extensive mutagenesis
      analysis predicts that the GC-rich region of the 5'UTR forms a constitutive
      translation barrier, which may prevent the ribosome from efficiently translating
      the BACE1 mRNA. Our data therefore demonstrate translational repression as a new
      mechanism controlling BACE1 expression.

PMID- 15167889
TI  - Cells defective for replication restart undergo replication fork reversal.
AB  - We have studied the fate of blocked replication forks with the use of the
      Escherichia coli priA mutant, in which spontaneously arrested replication forks
      persist owing to the lack of the major replication restart pathway. Such blocked
      forks undergo a specific reaction named replication fork reversal, in which newly
      synthesized strands anneal to form a DNA double-strand end adjacent to a four-way
      junction. Indeed, (i) priA recB mutant chromosomes are linearized by a reaction
      that requires the presence of the Holliday junction resolvase RuvABC, and (ii)
      RuvABC-dependent linearization is prevented by the presence of RecBC. Replication
      fork reversal in a priA mutant occurs independently of the recombination proteins
      RecA and RecR. recBC inactivation does not affect priA mutant viability but
      prevents priA chronic SOS induction. We propose that, in the absence of PriA,
      RecBC action at reversed forks does not allow replication restart, which leads to
      the accumulation of SOS-inducing RecA filaments. Our results suggest that types
      of replication blockage that cause replication fork reversal occur spontaneously.

PMID- 15167890
TI  - Molecular determinants of differential pore blocking of kidney CLC-K chloride
      channels.
AB  - The highly homologous Cl(-) channels CLC-Ka and CLC-Kb are important for water
      and salt conservation in the kidney and for the production of endolymph in the
      inner ear. Mutations in CLC-Kb lead to Bartter's syndrome and mutations in the
      small CLC-K subunit barttin lead to Bartter's syndrome and deafness. Here we show
      that CLC-Ka is blocked by the recently identified blocker 2-(p-chlorophenoxy)-3
      phenylpropionic acid of the rat channel CLC-K1 with an apparent K(D)
      approximately 80 microM. We also found that DIDS (4,4'-diisothiocyanatostilbene
      2,2'-disulphonic acid), a generic Cl(-) channel blocker, inhibits CLC-Ka (K(D)
      approximately 90 microM). Surprisingly, the highly homologous channel CLC-Kb is
      fivefold to sixfold less sensitive to both compounds. Guided by the crystal
      structure of bacterial CLC proteins, we identify two amino acids, N68/D68 and
      G72/E72, in CLC-Ka and CLC-Kb, respectively, that are responsible for the
      differential drug sensitivity. Both residues expose their side chains in the
      extracellular pore mouth, delineating the probable drug binding site. These novel
      CLC-K channel blockers are promising lead compounds for the development of new
      diuretic drugs.

PMID- 15167891
TI  - Fast, DNA-sequence independent translocation by FtsK in a single-molecule
      experiment.
AB  - Escherichia coli FtsK is an essential cell division protein, which is thought to
      pump chromosomal DNA through the closing septum in an oriented manner by
      following DNA sequence polarity. Here, we perform single-molecule measurements of
      translocation by FtsK50C, a derivative that functions as a DNA translocase in
      vitro. FtsK50C translocation follows Michaelis-Menten kinetics, with a maximum
      speed of approximately 6.7 kbp/s. We present results on the effect of applied
      force on the speed, distance translocated, and the mean times during and between
      protein activity. Surprisingly, we observe that FtsK50C can spontaneously reverse
      its translocation direction on a fragment of E. coli chromosomal DNA, indicating
      that DNA sequence is not the sole determinant of translocation direction. We
      conclude that in vivo polarization of FtsK translocation could require the
      presence of cofactors; alternatively, we propose a model in which tension in the
      DNA directs FtsK translocation.

PMID- 15167892
TI  - Crystal structure of the HGF beta-chain in complex with the Sema domain of the
      Met receptor.
AB  - The Met tyrosine kinase receptor and its ligand, hepatocyte growth factor (HGF),
      play important roles in normal development and in tumor growth and metastasis.
      HGF-dependent signaling requires proteolysis from an inactive single-chain
      precursor into an active alpha/beta-heterodimer. We show that the serine protease
      like HGF beta-chain alone binds Met, and report its crystal structure in complex
      with the Sema and PSI domain of the Met receptor. The Met Sema domain folds into
      a seven-bladed beta-propeller, where the bottom face of blades 2 and 3 binds to
      the HGF beta-chain 'active site region'. Mutation of HGF residues in the area
      that constitutes the active site region in related serine proteases significantly
      impairs HGF beta binding to Met. Key binding loops in this interface undergo
      conformational rearrangements upon maturation and explain the necessity of
      proteolytic cleavage for proper HGF signaling. A crystallographic dimer interface
      between two HGF beta-chains brings two HGF beta:Met complexes together,
      suggesting a possible mechanism of Met receptor dimerization and activation by
      HGF.

PMID- 15167893
TI  - RuvAB-directed branch migration of individual Holliday junctions is impeded by
      sequence heterology.
AB  - The Holliday junction, the key intermediate of recombination, is generated by
      strand exchange resulting in a covalent connection between two recombining DNA
      molecules. Translocation of a Holliday junction along DNA, or branch migration,
      progressively exchanges one DNA strand for another and determines the amount of
      information that is transferred between two recombining partners. In Escherichia
      coli, the RuvAB protein complex promotes rapid and unidirectional branch
      migration of Holliday junctions. We have studied translocation of Holliday
      junctions using a quantitative biochemical system together with a 'single
      molecule' branch migration assay. We demonstrate that RuvAB translocates the
      junctions through identical DNA sequences in a processive manner with a broad
      distribution of individual branch migration rates. However, when the complex
      encounters short heterologous sequences, translocation of the Holliday junctions
      is impeded. We conclude that translocation of the junctions through a sequence
      heterology occurs with a probability of bypass being determined both by the
      length of the heterologous region and the lifetime of the stalled RuvAB complex.

PMID- 15167894
TI  - The ribosomal protein Rps15p is required for nuclear exit of the 40S subunit
      precursors in yeast.
AB  - We have conducted a genetic screen in order to identify ribosomal proteins of
      Saccharomyces cerevisiae involved in nuclear export of the small subunit
      precursors. This has led us to distinguish Rps15p as a protein dispensable for
      maturation of the pre-40S particles, but whose assembly into the pre-ribosomes is
      a prerequisite to their nuclear exit. Upon depletion of Rps15p, 20S pre-rRNA is
      released from the nucleolus and retained in the nucleus, without alteration of
      the pre-rRNA early cleavages. In contrast, Rps18p, which contacts Rps15p in the
      small subunit, is required upstream for pre-rRNA processing at site A2. Most pre
      40S specific factors are correctly associated with the intermediate particles
      accumulating in the nucleus upon Rps15p depletion, except the late-binding
      proteins Tsr1p and Rio2p. Here we show that these two proteins are dispensable
      for nuclear exit; instead, they participate in 20S pre-rRNA processing in the
      cytoplasm. We conclude that, during the final maturation steps in the nucleus,
      incorporation of the ribosomal protein Rps15p is specifically required to render
      the pre-40S particles competent for translocation to the cytoplasm.

PMID- 15167895
TI  - A unique pathway for sustained neurotrophin signaling through an ankyrin-rich
      membrane-spanning protein.
AB  - A major question in cell biology is how molecular specificity is achieved by
      different growth factor receptors that activate apparently identical signaling
      events. For the neurotrophin family, a distinguishing feature is the ability to
      maintain a prolonged duration of signal transduction. However, the mechanisms by
      which neurotrophin receptors assemble such a sustained signaling complex are not
      understood. Here we report that an unusual ankyrin-rich transmembrane protein
      (ARMS+kidins220) is closely associated with Trk receptor tyrosine kinases, and
      not the EGF receptor. This association requires interactions between
      transmembrane domains of Trk and ARMS. ARMS is rapidly tyrosine phosphorylated
      after binding of neurotrophins to Trk receptors and provides a docking site for
      the CrkL-C3G complex, resulting in Rap1-dependent sustained ERK activation.
      Accordingly, disruption of Trk-ARMS or the ARMS-CrkL interaction with dominant
      negative ARMS mutants, or treatment with small interference RNA against ARMS
      substantially reduce neurotrophin-elicited signaling to ERK, but without any
      effect upon Ras or Akt activation. These findings suggest that ARMS acts as a
      major and neuronal-specific platform for prolonged MAP kinase signaling by
      neurotrophins.

PMID- 15167896
TI  - Coupling between snoRNP assembly and 3' processing controls box C/D snoRNA
      biosynthesis in yeast.
AB  - RNA polymerase II transcribes genes encoding proteins and a large number of small
      stable RNAs. While pre-mRNA 3'-end formation requires a machinery ensuring tight
      coupling between cleavage and polyadenylation, small RNAs utilize polyadenylation
      independent pathways. In yeast, specific factors required for snRNA and snoRNA 3'
      end formation were characterized as components of the APT complex that is
      associated with the core complex of the cleavage/polyadenylation machinery (core
      CPF). Other essential factors were identified as independent components: Nrd1p,
      Nab3p and Sen1p. Here we report that mutations in the conserved box D of snoRNAs
      and in the snoRNP-specific factor Nop1p interfere with transcription and 3'-end
      formation of box C/D snoRNAs. We demonstrate that Nop1p is associated with box
      C/D snoRNA genes and that it interacts with APT components. These data suggest a
      mechanism of quality control in which efficient transcription and 3'-end
      formation occur only when nascent snoRNAs are successfully assembled into
      functional particles.

PMID- 15167897
TI  - Reconstitution of a minimal mtDNA replisome in vitro.
AB  - We here reconstitute a minimal mammalian mitochondrial DNA (mtDNA) replisome in
      vitro. The mtDNA polymerase (POLgamma) cannot use double-stranded DNA (dsDNA) as
      template for DNA synthesis. Similarly, the TWINKLE DNA helicase is unable to
      unwind longer stretches of dsDNA. In combination, POLgamma and TWINKLE form a
      processive replication machinery, which can use dsDNA as template to synthesize
      single-stranded DNA (ssDNA) molecules of about 2 kb. The addition of the
      mitochondrial ssDNA-binding protein stimulates the reaction further, generating
      DNA products of about 16 kb, the size of the mammalian mtDNA molecule. The
      observed DNA synthesis rate is 180 base pairs (bp)/min, corresponding closely to
      the previously calculated value of 270 bp/min for in vivo DNA replication. Our
      findings provide the first biochemical evidence that TWINKLE is the helicase at
      the mitochondrial DNA replication fork. Furthermore, mutations in TWINKLE and
      POLgamma cause autosomal dominant progressive external ophthalmoplegia (adPEO), a
      disorder associated with deletions in mitochondrial DNA. The functional
      interactions between TWINKLE and POLgamma thus explain why mutations in these two
      proteins cause an identical syndrome.

PMID- 15167898
TI  - Prospero maintains the mitotic potential of glial precursors enabling them to
      respond to neurons.
AB  - During central nervous system development, glial cells need to be in the correct
      number and location, at the correct time, to enable axon guidance and neuropile
      formation. Repair of the injured or diseased central nervous system will require
      the manipulation of glial precursors, so that the number of glial cells is
      adjusted to that of neurons, enabling axonal tracts to be rebuilt, remyelinated
      and functional. Unfortunately, the molecular mechanisms controlling glial
      precursor proliferative potential are unknown. We show here that glial
      proliferation is regulated by interactions with axons and that the Drosophila
      gene prospero is required to maintain the mitotic potential of glia. During
      growth cone guidance, Prospero positively regulates cycE promoting cell
      proliferation. Neuronal Vein activates the MAPKinase signalling pathway in the
      glia with highest Prospero levels, coupling axon extension with glial
      proliferation. Later on, Prospero maintains glial precursors in an
      undifferentiated state by activating Notch and antagonising the p27/p21 homologue
      Dacapo. This enables prospero-expressing cells alone to divide further upon
      elimination of neurons and to adjust glial number to axons during development.

PMID- 15167899
TI  - Sensitizing glioma cells to cisplatin by abrogating the p53 response with
      antisense oligonucleotides.
AB  - Most gene therapy strategies related to p53 concentrate on the restoration of the
      activity of mutant p53, as several observations indicate that tumors and cell
      lines having the mutant gene are resistant to chemotherapy. However, as there is
      also some evidence to the contrary, we studied the relationship of the p53 status
      to the cellular response of glioma cells that were exposed to cisplatin. At a
      concentration of 2.5 microg/ml (which is about half the peak pharmacological
      blood level reached during chemotherapy), U373MG glioma cells, which had a mutant
      p53 gene, were more sensitive to the drug as compared to U87MG glioma cells (with
      normal p53). The U373MG cells responded with apoptosis while U87MG cells
      responded with a G2-M arrest. In U87MG cells, blocking the p53 response by
      antisense oligonucleotides also sensitized the cells to 2.5 microg/ml cisplatin,
      and shifted the cellular response from arrest to caspase 3-mediated apoptosis. A
      sensitive, p53-independent, mechanism for chemotherapy-induced apoptosis suggests
      that, in some cases, p53 abrogation by gene therapy or small molecule-based
      strategies could be a viable therapeutic strategy.

PMID- 15167900
TI  - Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed
      replication-competent adenovirus.
AB  - Although gene therapies using tissue-specific promoters have been reported to be
      a promising tool for treating cancers, few studies have explored this possibility
      for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was
      first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9
      protein is highly expressed in uterine cervical cancer tissues, but not in normal
      cervix, we constructed a tumor-specific replication-competent adenoviral vector
      utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9
      expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical
      cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein
      expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue
      specific replication of this recombinant adenovirus. In vitro cytotoxicity assay
      revealed that the growth of MN/CA9-positive cells was significantly inhibited
      with 0.01-1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC
      29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad
      MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These
      results suggest that a novel replication-competent adenoviral vector mediated by
      MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing
      tumors with cytotoxic effects and may be utilized for the treatment of uterine
      cervical cancer.

PMID- 15167902
TI  - Shaping developing tissues by apoptosis.

PMID- 15167901
TI  - Differential DNases are selectively used in neuronal apoptosis depending on the
      differentiation state.
AB  - In this study, we investigate the roles of two apoptotic endonucleases, CAD and
      DNase gamma, in neuronal apoptosis. High expression of CAD, but not DNase gamma,
      is detected in proliferating N1E-115 neuroblastoma cells, and apoptotic DNA
      fragmentation induced by staurosporine under proliferating conditions is
      abolished by the expression of a caspase-resistant form of ICAD. After the
      induction of neuronal differentiation, CAD disappearance and the induction of
      DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation
      that occurs under differentiating conditions is suppressed by the downregulation
      of DNase gamma caused by its antisense RNA. The induction of DNase gamma is also
      observed during neuronal differentiation of PC12 cells, and apoptotic DNA
      fragmentation induced by NGF deprivation is inhibited by the antisense-mediated
      downregulation of DNase gamma. These observations suggest that DNA fragmentation
      in neuronal apoptosis is catalyzed by either CAD or DNase gamma depending on the
      differentiation state. Furthermore, DNase gamma is suggested to be involved in
      naturally occurring apoptosis in developing nervous systems.

PMID- 15167903
TI  - Management of acute graft versus host disease (GvHD).
AB  - Graft versus host disease (GvHD) is a frequent complication of allogeneic
      hemopoietic stem cell transplantation (HSCT), and of donor lymphocyte infusions
      (DLI): the acute form occurs within 100 days from HSCT or DLI, the chronic form
      beyond day +100. GvHD should be prevented rather than treated. There are several
      ways to prevent GvHD: remove donor T cells from the transplant (ex vivo T-cell
      depletion), administer T-cell antibodies to the patient (in vivo T-cell
      depletion), administer immunosuppressive drugs such as methotrexate, cyclosporin,
      tacrolimus, and mycofenolate (post-transplant immunosuppression). New strategies
      of GvHD prophylaxis include the infusion of expanded mesenchymal stem cells and
      downregulation of host antigen-presenting cells. First-line treatment of
      established GvHD is based on low-dose corticosteroids (0.5-2 mg/kg). Second-line
      therapy for steroid refractory GvHD is unsatisfactory. The early administration
      of T-cell antibodies and/or TNF antibodies and TNF soluble receptor may be
      successful in some cases, but they do not seem to fulfill the expectations. High
      dose chemotherapy has not been explored thoroughly. Acute GvHD is complicated by
      infections that cause significant morbidity and mortality: prophylaxis, early
      diagnosis and treatment of infections are an integral part of GvHD management. We
      have considerably reduced the risk of acute GvHD over the past three decades: we
      need to further improve these results, with the final goal of dissecting, if
      possible, the graft versus host from the graft versus tumor effect.

PMID- 15167905
TI  - Beyond the International Prognostic Index: new prognostic factors in follicular
      lymphoma and diffuse large-cell lymphoma A meeting report of the Second
      International Lunenburg Lymphoma Workshop.

PMID- 15167904
TI  - Chronic lymphocytic leukaemia: new biological markers for assessing prognosis.
AB  - Well-established clinical staging systems continue to form a basis for deciding
      when to initiate treatment and assigning prognosis in chronic lymphocytic
      leukaemia. However, these staging systems do not identify those patients with
      early-stage disease who will progress to require treatment. Recent developments
      have provided a variety of prognostic markers, which can determine those patients
      with poor prognosis disease. For example, serum markers (soluble CD23), cell
      surface (CD38) and cytoplasmic (ZAP70) proteins, cytogenetics and immunoglobulin
      gene mutational status have all been utilised for this purpose. In order for
      patients to benefit fully from these discoveries they need to be translated into
      rapid, standardised and cost-effective clinical laboratory tests. The current
      range of prognostic markers, and techniques for measuring them are discussed.

PMID- 15167908
TI  - Outpatient-based peripheral blood stem cell transplantation for patients with
      multiple myeloma.
AB  - INTRODUCTION: There is a growing demand for autologous stem cell transplantation
      (ASCT) in newly diagnosed patients with multiple myeloma (MM), resulting in an
      increasing pressure on available hospital beds. In addition, more rational
      utilization of health resources should induce physicians to attempt therapeutic
      strategies aiming at reduction of costs. The aim of this study was to explore the
      feasibility and safety of performing ASCT on an outpatient basis, according to an
      early discharge method. MATERIALS AND METHODS: A total of 28 patients affected by
      MM and in complete or partial remission were selected to receive ASCT on an
      outpatient basis. In particular, after conditioning with high-dose melphalan and
      stem cell infusion, patients were programmed to go home and to be rehospitalized
      in the case of febrile neutropenia or other severe toxicities. RESULTS: All
      patients accepted the outpatient-based procedure. Out of 28 patients. 18 (64%)
      did spend the aplastic phase entirely at home following high-dose chemotherapy
      and stem cell infusion. A second hospital admission was required in 10 patients
      (36%). Febrile neutropenia and severe mucositis needing total parenteral
      nutrition were the most frequent causes of hospitalization. However, there were
      no documented infections and either fever or mucositis was easily resolved at the
      time of hematopoietic recovery in all patients. CONCLUSION: ASCT on an outpatient
      basis is feasible and safe in patients with MM. More than 60% of patients are
      manageable at home, provided that a caregiver is available.

PMID- 15167906
TI  - A phase II study of intensive chemotherapy with fludarabine, cytarabine, and
      mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes.
AB  - Since leukemic cells primed by exposure to fludarabine exhibit enhanced
      accumulation of cytarabine triphosphate (the cytotoxic nucleotide of cytarabine),
      especially with continuous cytarabine (AraC) infusion, a phase II trial was
      designed to explore the feasibility and efficacy of a combination chemotherapy
      associating fludarabine, mitoxantrone (MXN), and high-dose cytarabine (continuous
      infusion) for high-risk P glycoprotein (PGP)-negative myelodysplastic syndromes
      (MDS) (FAM protocol). The outcomes of FAM-treated patients were compared with
      those of 32 PGP-negative MDS patients fulfilling identical inclusion and response
      criteria treated with MXN+AraC (1 g/m(2)/12 h d(1-5), MA protocol). A total of 29
      patients (median age 55 years) were included in the FAM group. Six (21%) died
      from the procedure, and 16 (55%) achieved complete remission (CR). Of these, nine
      received consolidation chemotherapy, five were autografted and two were
      allografted in first CR. Abnormal karyotype was the only factor associated with
      poor survival. The overall median follow-up was 10.9 months. There was no
      significant difference between FAM and MA protocols with respect to CR rate,
      treatment-related mortality, duration of leukopenia, neutropenia, autologous stem
      cell transplantation feasibility, relapse-free survival, or overall survival. The
      duration of thrombocytopenia was significantly longer in the FAM protocol. In
      conclusion, the present results suggest that the combination therapy of
      fludarabine, MXN, and high-dose AraC does not improve CR rate, survival, or
      disease-free survival in high-risk MDS.

PMID- 15167907
TI  - Induction with oral chemotherapy (CID) followed by early autologous stem cell
      transplantation for de novo multiple myeloma patients.
AB  - In an effort to minimise induction therapy-related toxicity, avoid unnecessary
      hospitalisation and facilitate early ASCT, we have prospectively evaluated an
      outpatient-based oral chemotherapeutic regimen, cyclophosphamide, idarubicin,
      dexamethasone (CID) in patients with previously untreated multiple myeloma (mm).
      Patients subsequently underwent ASCT conditioned with melphalan 200 g/m(2). A
      total of 36 newly diagnosed MM patients were enrolled between February 1997 and
      March 2000. In all 136 cycles of CID were administered requiring only four
      unplanned hospital admissions. Grade 3 or 4 haematological toxicities were
      documented following 14 cycles (10%). There were no treatment-related deaths.
      Response rates (PR + CR) based on an intention-to-treat basis were 66% (23 of 35,
      9% CR) post-CID and 80% (28 of 35, 34% CR) post-ASCT. In all, 28 of the 35
      patients remain alive with a median follow-up for surviving patients of 40 months
      (range, 30-67 months). Progression-free survival from the time of diagnosis was
      32 months (range, 3-55+ months). Median overall survival from diagnosis has not
      been reached with an estimated overall survival at 4 years of 77%. CID in
      combination with early ASCT is an effective and well-tolerated antimyelomatous
      regimen and is a practical alternative to more toxic and invasive therapeutic
      approaches.

PMID- 15167909
TI  - Impact of immunophenotype on prognosis of patients with myelodysplastic
      syndromes. Its value in patients without karyotypic abnormalities.
AB  - The aim of this study was simultaneously to evaluate the potential influence of
      cytogenetic, immunophenotypic and cell culture studies in the evolution of the
      myelodysplastic syndromes (MDS) with particular attention to the value of the two
      latter features in predicting the outcome of those patients in which karyotypic
      information is normal or not available. A series of 77 newly diagnosed patients
      with primary MDS were analyzed. Immunophenotypic studies were carried out by flow
      cytometry in triple color combinations: CD34/CD33/CD38, CD15/CD34/HLADR and
      HLADR/CD13/CD45. In all, 63% of patients showed a normal karyotype and 37% showed
      clonal abnormalities. In immunophenotypic analysis, overall 90% of patients
      displayed phenotypic aberrations and 60% showed two or more aberrations. In
      univariate analysis, 10 variables had a significant influence on survival: >10%
      bone marrow (BM) blast cells, >or=peripheral blood (PB) cytopenias, >2% of BM
      CD34+ cells, >85% of BM myeloid cells, >7% monocytic cells, <49% of neutrophils,
      a neutrophil/monocytic cell ratio <7, more than three phenotypic aberrations and
      >80 colony-forming units for granulocytes and macrophages (CFU-GM)/10(5) plated
      cells. Only the presence of >or=5% of BM blast cells (P=0.001) and cytogenetic
      subgroups (P=0.008) showed independent prognostic significance by multivariate
      analysis. In patients lacking cytogenetic information or in which the karyotype
      was normal additional markers had an independent prognostic value in multivariate
      analysis: >or=2 phenotypic aberrations (P=0.001) and >or=2 PB cytopenias
      (P=0.004). In summary, our results show that in patients in whom the karyotype is
      normal or where an insufficient amount of mitoses is obtained, immunophenotype
      could help to establish a prognosis.

PMID- 15167910
TI  - Platelet function and its clinical significance in the myelodysplastic syndromes.
AB  - The current study was aimed at investigating platelet function in MDS and its
      clinical significance. There were 23 patients with untreated MDS at presentation,
      including refractory anemia (RA), RA with ringed sideroblasts, RA and excess
      blasts and chronic myelomonocytic leukemia RAEBt. The mean platelet count was
      167.9 x 109/L. Patients with a platelet count less than 70 x 109/l were excluded.
      The mean bleeding time (BT) was 2.7 min. Only four MDS patients had BT longer
      than the normal 1-4 min range. Platelet aggregation (PA) was studied with
      epinephrine (Epi), ADP, arachidonic acid (AA), ristocetin and collagen. Overall,
      16 (70%) patients had PA abnormality, 65% had impaired Epi-induced PA, 57%
      demonstrated reduced ADP-induced PA. AA, ristocetin and collagen was decreased PA
      in 48, 22 and 17%, respectively. Five patients (22%) demonstrated spontaneous PA.
      Only seven patients (30%) were found to have normal PA with all five inducers.
      Six (26%) patients had spontaneous mild bleeding and all six bleeding MDS
      patients demonstrated at least one abnormal platelet function. The only bleeding
      patient with all five PA tests normal demonstrated prolonged BT. In the present
      study of 23 newly diagnosed MDS patients, PA abnormalities were relatively
      common, the BTs were usually normal, and bleedings were relatively uncommon and
      mild at platelet count between 70 and 397 x 109/l.

PMID- 15167911
TI  - FLT3-activating mutations are associated with poor prognostic features in AML at
      diagnosis but they are not an independent prognostic factor.
AB  - FLT3: gene alterations (internal tandem duplications - ITDs - and D835 mutations)
      are thought to be associated with poor-risk acute myeloid leukemia (AML).
      However, not all studies confirm this association, so it is still a matter of
      debate. Moreover, their association with other molecular abnormalities is less
      studied. We have investigated the presence of FLT3-ITD and D835 mutations in AML
      patients and their correlation with clinical and biological disease
      characteristics. The presence of ITD was analyzed in diagnostic samples of 176
      AML patients and the D835 mutation in 135 of these patients. In all these
      patients, the presence of four well-known molecular abnormalities were also
      simultaneously characterized: PML/RARalpha, AML1/ETO, CBFbeta/MYH11 and MLL
      rearrangements. In all, 41 (23%) patients harbored FLT3 mutations, with 34
      (19.3%) of them positive for the ITD, and seven (5%) positive for the D835
      mutation. Of the acute promyelocytic leukemia (APL) patients, 16 (27%) showed
      FLT3 mutations, more frequently in M3 hypogranular cases (62% versus 17%,
      P=0.001) and cases with the short (bcr3) PML-RARalpha isoform (69%, P=0.002). In
      contrast, FLT3 was never altered in patients with inv(16), t(8;21) or 11q23
      abnormalities. FLT3 mutations were significantly associated with some negative
      prognostic features at diagnosis (leukocytosis, high blast-cell percentage, and
      elevated LDH values), but they were not associated with different disease-free or
      overall survival. Therefore, we confirm a high frequency of FLT3 mutations in APL
      and in adult AML without recurrent cytogenetic translocations. In addition, they
      were not found as independent prognostic factors although associated with several
      adverse features at diagnosis.

PMID- 15167912
TI  - s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple
      myeloma cell line.
AB  - s-Thalidomide has proven efficacy in multiple myeloma. Although it has both
      antiangiogenic and pro-apoptotic effects, its primary mode of therapeutic action
      remains unclear. We have investigated the changes to the expression of genes
      involved with these cellular processes following culture with s-thalidomide in
      the U266 MM cell line. Cells were cultured with s-thalidomide (0-1000 microM),
      and cell parameters, including apoptosis, were assessed on day 3. RNA was
      extracted from cells cultured for 24 h at the IC(50) concentration of s
      thalidomide, and changes to gene expression were investigated by microarray
      methodologies. A reduction in cell viability was observed in U266 cells cultured
      with s-thalidomide (IC(50): 362 microM), which were mirrored by significant
      increases in apoptosis (for example, 200 microM on day 3: 40.3+/-3.1% vs. 3.2+/
      0.4% on day 0; P<0.001). There were changes in the expression profile of genes
      involved in angiogenesis and apoptosis, but the changes were most dramatic in the
      apoptotic genes. In particular, the expression of I-kappaB kinase was decreased
      by two-fold, which was associated with a four-fold decrease in NF-kappaB
      expression. These data correlated with immunoblotting analyses, which showed
      significant increases in I-kappaB protein levels and decreased NF-kappaB
      activity. Additionally, the Bax : Bcl-2 ratio was significantly increased. Our
      data suggest that both angiogenic and apoptotic genes and proteins are affected
      by s-thalidomide. Additionally, a dramatic decrease in Bcl-2 expression with s
      thalidomide suggests a possible enhancement of cytotoxic effect if combined with
      other cytotoxic agents.

PMID- 15167913
TI  - Is there a direct effect of antithymocyte globulin on hematopoiesis?
AB  - The efficacy of immunosuppressive therapy in aplastic anemia (AA) provides the
      strongest argument to support its immune-mediated pathophysiology. While several
      immunosuppressive effects of antithymocyte globulin (ATG) can be demonstrated in
      vitro, some reports have implied that the activity of ATG in AA may be rather due
      to a variety of positive hematopoietic effects. We studied the effects of horse
      (h) and rabbit (r) ATG on marrow progenitors in vitro. Both types of ATG bound to
      CD34 cells and, in colony assays performed with total marrow cells, hATG had a
      dose-dependent, triphasic effect, with maximal increase in colony formation
      between 1 and 10 microg/ml and inhibition between 100 and 1000 microg/ml. As
      determined using CD34 cells, these effects did not require accessory cells. rATG
      showed similar activity, but was about 10-fold more potent than hATG. In the
      presence of complement, no increased cytotoxicity was observed. At concentrations
      equivalent to those measured in patients immediately after infusion, ATG showed
      moderate suppression of colony formation, while the stimulatory concentrations in
      vitro correspond to those seen in vivo within the first weeks after ATG
      administration. In control experiments, the patterns of the biologic effects of
      preimmune rIgG or hIgG preparations were similar to those of rATG and hATG,
      indicating a nonspecific nature of the effects of ATG on progenitor cells.
      Biological activity in methylcellulose cultures was observed with the F(ab)(2)
      fragments but was not found in purified Fc IgG. In summary, the spectrum of
      effects of ATG on hematopoietic progenitors is dependent upon the concentrations
      of ATG and may not be related to its antigenic specificity.

PMID- 15167914
TI  - Involvement of mitogen-activated protein kinase in the cytokine-regulated
      phosphorylation of transcription factor GATA-1.
AB  - Gene-targeting experiments in transgenic mice have revealed an essential role for
      GATA-1 in the normal differentiation and development of erythroid cells. GATA-1
      is phosphorylated in vivo on seven of its serine residues; the regulation and
      function of GATA-1 phosphorylation, however, is not understood. Here we
      demonstrate a role for MAP kinase (MAPK) signalling in the control of GATA-1
      phosphorylation. We show that EGF-induced MAPK signalling results in the
      phosphorylation of ectopically expressed GATA-1 in COS cells. This
      phosphorylation can be positively or negatively regulated by genetic manipulation
      of the MAPK pathway through expression of constitutively activated, or dominant
      negative, mutants of MAPK kinase (MAPKK), an upstream regulator of MAPK activity.
      In vitro phosphorylation experiments using purified MAPK and either recombinant
      GATA-1 or synthetic GATA-1 peptides suggest that GATA-1 is a MAPK substrate with
      MAPK phosphorylation occurring primarily on Ser26 and Ser178. We also show that
      GATA-1 is phosphorylated in factor-dependent haemopoietic progenitor cells in
      response to cytokine-induced signalling. Through the further use of a dominant
      negative MAPKK mutant as well as chemical inhibitors of specific MAPKs, we
      identify ERK as an in vivo GATA-1 kinase. Finally, we demonstrate that mutation
      of serines 26 and 178 compromises the ability of GATA-1 to interact with the LIM
      only protein LMO2 when both proteins are expressed in COS cells. These data
      implicate receptor-mediated signalling through the MAPK pathway as a control
      point in the regulation of transcription factor GATA-1.

PMID- 15167915
TI  - Chronic myelogenous leukemia with acquired c-kit activating mutation and
      transient bone marrow mastocytosis.
AB  - Mutations of the c-kit gene have been reported in myeloproliferative disorders.
      We describe here a case of Ph+ (b2a2) chronic myelogenous leukemia that, during
      the course of disease, showed an unusual bone marrow mast-cell infiltration. A
      mutational screening for the c-kit gene, performed on DNA routinely cryopreserved
      during the follow-up, evidenced the D816Y-activating mutation as an additional
      genetic abnormality. Treatment with imatinib mesylate resulted in a substantial
      decrease of the BCR-ABL/ABL ratio and in the absence of c-kit mutation. It is
      likely that the superimposed c-kit mutation, in this case, may account for the
      transient bone marrow mastocytosis.

PMID- 15167916
TI  - Balance between acute graft-versus-host disease and graft-versus-tumor effect
      after reduced-intensity transplantation for metastatic renal cell carcinoma.
AB  - We describe a patient who had received reduced-intensity stem cell
      transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old
      man developed rapid progression of RCC during steroid therapy for immune-mediated
      thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of
      corticosteroid, RCC achieved long stable disease with the presence of chronic
      GVHD, despite low dose of prednisolone. This case suggests the impact of
      immunosuppression on progression of metastatic RCC after RIST.

PMID- 15167917
TI  - A single administration of gemtuzumab ozogamicin for molecular relapse of acute
      promyelocytic leukemia.

PMID- 15167918
TI  - Severe gastrointestinal haemorrhage responding to recombinant factor VIIa in a
      Jehovah's Witness with refractory immune thrombocytopenia.

PMID- 15167919
TI  - Fludarabine as the possible cause of acute myelofibrosis.

PMID- 15167921
TI  - The unexamined 'Caucasian'.

PMID- 15167922
TI  - A public gene trap resource for mouse functional genomics.

PMID- 15167923
TI  - Inauguration of the African Society of Human Genetics.

PMID- 15167925
TI  - Shocking degeneration.

PMID- 15167926
TI  - Sex and the genome.

PMID- 15167927
TI  - Fine-tuning PU.1.

PMID- 15167928
TI  - Plzf pushes stem cells.

PMID- 15167929
TI  - Huntingtin aggregates ask to be eaten.

PMID- 15167932
TI  - A probabilistic view of gene function.
AB  - Cells are controlled by the complex and dynamic actions of thousands of genes.
      With the sequencing of many genomes, the key problem has shifted from identifying
      genes to knowing what the genes do; we need a framework for expressing that
      knowledge. Even the most rigorous attempts to construct ontological frameworks
      describing gene function (e.g., the Gene Ontology project) ultimately rely on
      manual curation and are thus labor-intensive and subjective. But an alternative
      exists: the field of functional genomics is piecing together networks of gene
      interactions, and although these data are currently incomplete and error-prone,
      they provide a glimpse of a new, probabilistic view of gene function. We outline
      such a framework, which revolves around a statistical description of gene
      interactions derived from large, systematically compiled data sets. In this
      probabilistic view, pleiotropy is implicit, all data have errors and the
      definition of gene function is an iterative process that ultimately converges on
      the correct functions. The relationships between the genes are defined by the
      data, not by hand. Even this comprehensive view fails to capture key aspects of
      gene function, not least their dynamics in time and space, showing that there are
      limitations to the model that must ultimately be addressed.

PMID- 15167933
TI  - Human genes that limit AIDS.
AB  - Discernable genetic variation among people and populations has an important role
      in infectious disease epidemics, including that of acquired immune deficiency
      syndrome (AIDS). Genetic association analysis of several large AIDS cohorts
      implicate 14 AIDS restriction genes, polymorphic variants in loci that regulate
      HIV-1 cell entry, acquired and innate immunity, and cytokine defenses to HIV-1.
      The influence and translational impact of these genes on individual and
      population sensitivity to AIDS is considerable.

PMID- 15167935
TI  - CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized
      from nonmetastasized sporadic pheochromocytomas.
AB  - The natural course of pheochromocytomas (PCC) cannot be predicted for certain on
      the basis of primary histology, their malignant character can only be confirmed
      by the occurrence of metastases during follow-up. Based on the recently proposed
      PASS score for evaluation we examined 37 adrenal (36 sporadic and one familial)
      and six sporadic extra-adrenal paragangliomas (all designated as
      pheochromocytomas) with a 'malignant histology' to find additional predictive
      factors. Drawing upon the follow-up (18 months to 12 years, mean 5.8 years)
      metastasized (n=20) and nonmetastasized (n=23) courses could be distinguished.
      Metastasized PCC revealed significantly (P=0.03) more copy number changes on
      comparative genomic hybridization (CGH) (mean 8.3) than nonmetastasized tumors
      (mean: 4.3). The most frequent chromosomal alterations were losses on 1p (75.6%)
      and 3q (44%). Both were detected with identical frequency in metastasized and
      nonmetastasized PCC. A gain on 17q (P=0.025) was significantly predominant in
      malignant courses and suggests similarities in the genetic origin and progression
      of PCC and neuroblastomas. The proliferative activity (MIB-1 score) of
      metastasized PCC (n=20) was found to be significantly higher in metastasized
      tumors (mean 12.8% vs mean 3.5%). In contrast, the semiquantitatively scored
      membrane-bound staining of CD 44-S was stronger in tumors without metastases
      (mean 2.1 vs mean: 0.25) during the follow-up period (P<0.01). Although the
      results correspond to the established weight differences the tumor weight does
      not appear to be an independent prognostic factor. Our study suggests that CD 44
      S and MIB-1 immunostaining as well as the CGH results might complement the PASS
      score in predicting a metastasized course of PCC. Regardless of tumor weight,
      tumors with a 'malignant histology' are highly prone to metastasize when more
      than 5% of MIB1-positive nuclei are present or CD44-S immunostaining is negative,
      or both. PCC with 10 or more copy number changes on CGH must be referred to as
      malignant tumors.

PMID- 15167936
TI  - Improved 1-h rapid immunostaining method using intermittent microwave
      irradiation: practicability based on 5 years application in Toyama Medical and
      Pharmaceutical University Hospital.
AB  - Immunostaining depending on antigen-antibody specificity is the commonest
      approach for determining the localization of specific antigens in tissue
      sections. This procedure is applicable not only with frozen or specially fixed
      samples, but also has proved reliable with formalin-fixed paraffin-embedded
      tissue sections through improvement of antigen-retrieval. Immunostaining is thus
      firmly established as a tool for diagnostic pathology and in our institute
      multiple antibodies are applied for 13-15% of the cases examined, as well as H
      and E staining. With the standard approach, approximately 3 h is necessary from
      the beginning of deparaffinization till covering sections with the Envision
      system. We utilized intermittent microwave irradiation for 10 min during
      hybridization with primary and secondary antibodies in a special moist-chamber,
      to achieve all immunostaining steps within 1 h in 178 primary antibodies
      frequently used for diagnostic pathology. According to our 5 years experience,
      such microwave irradiation not only obtained significant specific staining for
      enhancing the specificity of antigen-antibody reactions, but also inhibited
      nonspecific binding. We present herein the details of the methodology and
      recommendations for its application with particular primary antibodies. This
      method can contribute to savings in time and energy, allowing pathologists to
      rapidly obtain diagnostic information.

PMID- 15167937
TI  - Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor
      expression in early stage conventional adenocarcinoma and bronchioloalveolar
      carcinoma of the lung.
AB  - In this study, we investigated the prognostic value of HER2/neu, p53, and
      vascular endothelial growth factor in early stage conventional adenocarcinoma and
      bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted
      of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar
      carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were
      immunostained for HER2/neu, p53, and vascular endothelial growth factor.
      Positivity was scored quantitatively by three observers and correlated with
      multiple prognostic parameters including survival. In the conventional
      adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were
      expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group,
      p53 showed a significant correlation with recurrence while vascular endothelial
      growth factor correlated with angiolymphatic invasion (P < 0.05). HER2/neu, p53,
      and vascular endothelial growth factor expression was associated with
      significantly shorter survival (log rank, P < 0.05). Patient whose tumors
      coexpressed both p53 and HER2/neu had the worst outcome. In the
      bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth
      factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively
      which was significantly less than in conventional adenocarcinoma (P < 0.05).
      HER2/neu positivity showed a significant correlation with shorter survival (log
      rank, P < 0.05) in nonmucinous type. In conclusion, vascular endothelial growth
      factor was associated with angiolymphatic invasion and poor prognosis in
      conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and
      HER2/neu expression appeared to be poor prognostic markers, while in
      bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer
      prognosis. This immunostaining pattern suggests that conventional adenocarcinoma
      has different molecular abnormalities than bronchioloalveolar carcinoma.

PMID- 15167938
TI  - Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and
      without intestinal (Barrett's) metaplasia.
AB  - Barrett's esophagus is diagnosed when goblet cells are found in the lower
      esophageal mucosa. However, the distribution of these cells is patchy and they
      may not represent the earliest marker of intestinal metaplasia. Cdx2 is a
      transcription factor whose expression in normal tissues is restricted to
      intestinal-type epithelium. Its distribution in the columnar-lined esophagus with
      and without intestinal metaplasia has been seldom studied. We evaluated Cdx2
      expression in lower esophageal biopsies from 90 patients with endoscopic
      diagnosis of short segment Barrett's esophagus, including 45 consecutive cases
      showing intestinal metaplasia (goblet cells present in hematoxylin eosin and/or
      Alcian blue stains) and 45 consecutive cases without goblet cells. 25 samples of
      cardiac-type mucosa without intestinal metaplasia biopsied from the stomach
      served as controls. All cases with intestinal metaplasia revealed Cdx2 reactivity
      in goblet cells and adjacent nongoblet columnar cells. Dysplastic foci, seen in
      five cases from this group, were Cdx2 positive. In the group without goblet
      cells, Cdx2 was focally expressed by columnar cells in 17 (38%) cases. All
      control cases were Cdx2 negative. Strips of Alcian blue-positive nongoblet
      columnar cells ('columnar blues') were observed in 11 (24%) of the cases without
      intestinal metaplasia. All these foci were Cdx2 negative. In conclusion, Cdx2 is
      a highly sensitive marker for Barrett's esophagus. It is also expressed in a
      significant minority of cases of columnar-lined esophagus without goblet cells,
      suggesting that it may detect intestinal phenotypic modifications in the absence
      of goblet cells. Accordingly, Cdx2 immunostaining could help identify patients
      with Barrett's metaplasia in cases where no goblet cells are visible in biopsies
      from the columnar-lined esophagus. Finally, lack of Cdx2 expression in the
      'columnar blues' suggests that these cells are not diagnostic of intestinal
      metaplasia.

PMID- 15167939
TI  - Fluorescence in situ hybridization analysis of chromosome 12p in paraffin
      embedded tissue is useful for establishing germ cell origin of metastatic tumors.
AB  - The over-representation of chromosome 12p sequences is crucial for the
      development of invasive testicular germ cell tumors. Testicular cancer patients
      may have metastatic tumors of diverse histologic types, including adenocarcinoma,
      undifferentiated carcinoma, sarcoma, or other malignancies that lack features of
      germ cell tumors. We sought to investigate the possible germ cell origin of such
      tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic
      malignant somatic-type tumors from patients with histories of testicular cancer,
      as well as one malignant somatic-type tumor from a patient with primary
      mediastinal germ cell tumor were studied and included: adenocarcinoma (five
      cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine
      carcinoma (one). The tumors were analyzed using fluorescence in situ
      hybridization using 12p spectrum green and 12 centromeric spectrum orange probes
      in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43).
      Colon and lung cancers from patients without germ cell tumors were used as
      controls. Adequate signals were observed in all tumors. Gain of chromosome 12p
      was seen in six tumors. None of the control tumors showed 12p amplification.
      Fluorescence in situ hybridization for 12p amplification in routinely processed
      surgical specimens is a useful adjuvant diagnostic tool in confirming the germ
      cell origin of metastatic tumors having the histologic appearance of somatic-type
      neoplasms.

PMID- 15167941
TI  - Clinical holistic medicine: the "new medicine", the multiparadigmatic physician,
      and the medical record.
AB  - The modern physician is often multiparadigmatic as he serves many different types
      of people in many different existential circumstances. The physician basically
      often has three, very different sets of technologies or "toolboxes" at his
      disposal, derived from three different medical paradigms: classical, manual
      medicine; biomedicine; and holistic or consciousness-oriented medicine. For lack
      of a better term, we have called the extended medical science--integrating these
      three different paradigms and their three strands of tools and methods--the "new
      medicine". The excellent physician, mastering the "new medicine", uses the most
      efficient way to help every patient, giving him or her exactly what is needed
      under the circumstances. The excellent physician will choose the right
      paradigm(s) for the person, the illness, or the situation, and will use the case
      record to keep track of all the subjective and objective factors and events
      involved in the process of healing through time. The case or medical record has
      the following purposes: A. REFLECTION: To keep track of facts, to provide an
      overview, to encourage causal analysis, to support research and learning, and to
      reveal mistakes easily. B. COMMUNICATION: To communicate with the patient with a
      printout of the case record to create trust and help the patient to remember all
      assignments and exercises. C. EVIDENCE AND SAFETY: To provide evidence and safety
      for the patient or to be used in case of legal questions. D. SELF-DISCIPLINE: To
      encourage discipline, as a good case record is basically honest, sober, brief,
      and sticks to the point. It forces the physician to make an effort to be more
      diligent and careful than a busy day usually allows. The intention of the case or
      medical record is ethical: to be sure that you, as a physician, give the best
      possible treatment to your patient. It helps you to reflect deeply, communicate
      efficiently, provide evidence and safety, and back your self-discipline, never to
      be carried away by the high speed of modern-day clinical work to give less than
      the optimal treatment. The patient"s life, now and in the future, is in the palm
      of your hand, and to assume this huge responsibility, the physician must be
      anxious and careful about the quality of the medical record. Much too often, the
      essence of the session is nowhere to be found in the case record, so most of the
      generated value is lost between consultations.

PMID- 15167940
TI  - Clinical holistic medicine: a pilot study on HIV and quality of life and a
      suggested cure for HIV and AIDS.
AB  - This study was undertaken to examine the association between the immunological
      impact of HIV (measured by CD4 count) and global self-assessed quality of life
      (QOL) (measured with QOL1) for people suffering from HIV, to see if the
      connection was large and statistically strong enough to support our hypothesis of
      a strong QOL-immunological connection through the nonspecific, nonreceptor
      mediated immune system, and thus to give a rationale for a holistic cure for HIV.
      This cross-sectional population study in Uganda included 20 HIV infected persons
      with no symptoms of AIDS and a CD4 count above 200 mill./liter. The main outcome
      measures were CD4 count, global QOL measured with the validated questionnaire
      QOL1, translated to Luganda and translated back to English. We found a large,
      clinically significant correlation between the number of T-helper cells (CD4) and
      global self-assessed quality of life (QOL1) (r = 0.57, p = 0.021), when
      controlled for age, gender, and years of infection. Together with other studies
      and holistic medicine theory, the results have given rationale for a holistic
      cure for HIV. We suggest, based on our findings and theoretical considerations,
      that HIV patients who improve their global QOL, also will improve their CD4
      counts. Using the technique of holistic medicine based on the life mission theory
      and the holistic process theory of healing, we hypothesize that the improvement
      of QOL can have sufficient biological effect on the CD4, which could avoid or
      postpone the development of AIDS. A holistic HIV/AIDS cure improving the QOL
      draws on hidden resources in the person and is thus affordable for everybody.
      Improving global QOL also means a higher consciousness and a more ethical
      attitude, making it more difficult for the HIV-infected person to pass on the
      infection.

PMID- 15167942
TI  - Clinical holistic medicine: social problems disguised as illness.
AB  - Many of the diseases seen in the clinic are actually symptoms of social problems.
      It is often easier for the physician to treat the symptoms than to be a coach and
      help the patient to assume responsibility in order to improve quality of life,
      social situation, and relations. If the physician ignores the signs of the
      disease as a symptom of social problems, and treats the patient with
      pharmaceuticals, he can give the patient the best justification in the world not
      to do anything about the situation. It is very important that the physician is
      not tricked by the games the socially troubled patient, more or less
      unconsciously, is playing. A firm and wise attitude that confronts the patient
      with his or her lack of responsibility for solving social problems seems to be a
      constructive way out. The physician can give holding and support, but the
      responsibility must remain with the patient. Often it is better for the patient
      that the physician abstains from giving drugs that can remedy the symptoms and
      takes the role of a coach instead. Suffering is not necessarily bad, suffering is
      actually highly motivating and often the most efficient source of learning.
      Coaching can help the patient canalize his motivation into highly constructive
      considerations and behavior. A holistic approach thus gives the patient learning
      and helps him rehabilitate his social reality. Concerning children with recurrent
      or chronic pain, we have observed an overuse of painkillers, where we believe
      part is of a psychosomatic nature due to poor thriving in the family. Here the
      physician has an important job helping the parents to develop as persons,
      teaching them the basic holding of awareness, respect, care, acknowledgment and
      acceptance of their child. Most of the chronic pain and discomfort with children
      can be improved if the physician understands how to use the holistic medical
      toolbox.

PMID- 15167944
TI  - Snoezelen or controlled multisensory stimulation. Treatment aspects from Israel.
AB  - In Israel today, with a total population of over 6 million persons, the Division
      for Mental Retardation (DMR) provides services to 23,000 persons with
      intellectual disability (ID). Of the 23,000, residential services are provided to
      more than 6,000 in close to 60 residential centers, another 2,000 are provided
      residential care in hostels or group homes in the community in about 50
      locations, while the rest are served with day-care kindergarten, day-treatment
      centers, sheltered workshops, or integrated care in the community. The first
      Snoezelen room (controlled multisensory stimulation) in the DMR was established
      at the Bnei Zion residential care center in 1995. The Snoezelen method is now
      used in Israel in more than 30 residential care centers and 3 community settings.
      Since the year 2000, a physiotherapist has been employed in order to supervise
      the treatment and development of the method nationally. Professional staff
      meetings take place every 4 months. A certification course has been established
      on a national basis for individuals from different professions (occupational
      therapists, physiotherapists, teachers, music therapists, nurses, speech
      therapists, or caregivers). Snoezelen has proved to be an important instrument
      and a powerful therapeutic tool among the various treatment modules employed in
      Israel for persons with ID. This paper presents the concept illustrated with two
      case stories.

PMID- 15167943
TI  - Clinical holistic medicine: use and limitations of the biomedical paradigm.
AB  - The biomedical paradigm is so convincing from a biochemical point of view, and
      highly efficient in many cases of acute medical problems and emergencies, but
      unfortunately most patients do not get much better only treated with drugs; they
      need to do something about their lives themselves. It is highly important for the
      modern physician to understand the strengths and weaknesses of the modern
      biomedical paradigm, to understand when and when not to administer drugs to their
      patients. Often a symptom can be eliminated for a while with drugs, but this is
      not always good as the patient might need to learn to study the imbalances in
      life that cause the disturbances and symptoms. For the elderly patient, sometimes
      life can be extended in spite of the subjective fact that life has come to its
      end. Sometimes treatment with a drug can teach the patient that quality of life
      is the responsibility of the physician and not the patient. This learned attitude
      can give the patient problems later or make them less active in helping
      themselves (responsibility transfer in the wrong direction). This paper gives a
      number of examples where medical drugs really are the treatment of choice in
      general practice and some more doubtful examples of using of the biomedical
      paradigm.

PMID- 15167945
TI  - Historical transition of eco-structure in a tidal flat caused by expansion of
      sewerage treatment area.
AB  - An artificial tidal flat was prepared for the mitigation tool on coastal
      environment. However, it is considered that most of the flat was not restored to
      the sufficient amenities for aquatic living things, migratory birds, etc. because
      none of the ecological mechanisms were understood or planned for. It is therefore
      investigated in this paper that historical transition factors in ecosystem
      structure are selected and traced with the diffusion of a public sewerage system,
      and with environmental factors such as water quality, sediment condition, and
      aquatic producers in the Yatsu Tidal Flat. As a result, it can be defined that
      the tidal flat, just like a lagoon, was formed artificially with reclamation and
      development of its circumference at the first step of transition; the water
      quality and sediment condition gradually became brackish water and muddy sediment
      conditions, interactively. The ecosystem pyramid forming orderly layers according
      to trophic level appeared as a high-bio-production potential in its tidal flat.
      In the second step, i.e., in recent years, the characteristics of water quality
      and sediment conditions evolved into a foreshore tidal flat, namely, conditions
      in the flat observed were that the progression of water included a high
      concentration of chloride ion as seawater and sediment conditions became sandy.
      Because of that, the inflowing fresh water and organic mater from the land area
      decreased with the improvement of the public sewerage system. The ecosystem
      pyramid was distorted into a chaos pyramid, with inversion of Ulva spp.

PMID- 15167946
TI  - The Arab community in Israel coping with intellectual and developmental
      disability.
AB  - The Arab family in Israel is still embedded in the traditional society with
      extended family support systems, but we see a population in transition influenced
      by the surrounding society. This paper looks at the different religious attitudes
      toward the exceptional people in our society (i.e., the family reaction to a
      child born with intellectual or developmental disability), reviews recent studies
      on the Arab and Bedouin families in Israel, and presents data on the Arab
      population in residential care centers. Today, out of 57 residential care centers
      in Israel for persons with intellectual disability, 13 (22.8%) are providing
      service to the non-Jewish population. The Arab population constitutes 12-13% of
      the total residential care population, lower than the 19-20% in the total
      population. In residential care, the Arab population is characterized by younger
      children with severe and profound intellectual disability. The informal family
      support system is still a very important factor in the Arab family in Israel, a
      fact that we believe should be strengthened by implementing the British and
      Danish model of nurse home visitation.

PMID- 15167947
TI  - [Responsibility of the anaesthetist in preoperative risk management. Comments on
      the legal implications of medical publications in this field].
AB  - There is an increasing number of publications in the medical literature which
      address the medical and legal obligations of a specialist in a given field. These
      articles, mostly editorials, seek to delineate the optimal course of treatment
      based on the current state of the art and science of medicine. However, we
      believe that the unreflected adoption of these often highly theoretical ideas and
      suggestions carries its own dangers. For one thing, there is the threatening
      financial crisis in the public health system. In addition, the feasibility of
      implementing these suggestions in routine medical and surgical practice is
      questionable. Last but not least, suggestions and guidelines for preoperative
      risk management by, for instance, Lingnau and Strohmenger 2002 cross the well
      established boundaries of the various medical and surgical specialties, which
      obviously demands careful deliberations among the specialties involved. So far,
      few specialty boards have seen fit to act on these suggestions. Our article on
      the medical and legal responsibilities of the anaesthesiologist in perioperative
      risk management restates the aforementioned concerns. We attempt to point out
      medical and legal points of controversy. In particular, we caution against the
      ever present danger of a bona fide adoption of visionary guidelines as the
      "standard of care" by both medical and legal experts. We feel that it is
      imperative to carefully evaluate editorial comments and suggestions, however well
      meaning, in the light of established teaching and practice, lest these comments
      and suggestions become the basis of an unjustified determination of a physicians
      innocence or guilt in a court of law.

PMID- 15167949
TI  - [From hypertension to heart failure-a pathophysiological continuum].
AB  - The heart failure syndrome is one the most common chronic diseases in western
      countries with poor prognosis. In view of the estimated aging of our society, it
      will gain further importance. Hypertension and/or myocardial infarction are the
      main causes of chronic heart failure, accounting for about three quarters of the
      cases. In hypertension, pressure overload of the heart leads to an increase in
      wall stress. This frequently results in cardiac hypertrophy, which is induced by
      the mechanical stress on the cardiomyocytes and the activation of neuroendocrine
      mechanisms, particularly the renin-angiotensin-aldosterone system and the
      sympathetic nervous system. Myocardial hypertrophy represents an independent risk
      factor for cardiovascular events and is a powerful predictor for the development
      of heart failure. The signal transduction pathways leading to the transition from
      compensated hypertrophy to heart failure are subject of intensive research. The
      knowledge of the maladaptive signaling pathways may be the basis for new
      therapeutic strategies in the prevention and management of heart failure.

PMID- 15167948
TI  - [Laryngeal tube versus laryngeal mask airway in anaesthetised non-paralysed
      patientsA comparison of handling and postoperative morbidity].
AB  - BACKGROUND: The purpose of this study was to compare the classical laryngeal mask
      airway (LMA) with the laryngeal tube (LT) in anaesthetised non-paralysed
      patients. PATIENTS AND METHODS: A total of 100 patients scheduled for minor
      elective surgery were included. After standardised induction and maintenance of
      anaesthesia with propofol and remifentanil, patients were randomly allocated to
      receive either a LMA or LT; muscle relaxants were not applied. Selection of the
      appropriate size and the initial inflation volume were chosen according to the
      manufacturers instructions. Ease of insertion, initial intra-cuff pressure,
      oropharyngeal leak pressure at an intra-cuff pressure of 60 cm H(2)O and
      incidence and severity of complications during and after anaesthesia were
      compared. RESULTS: The LT was inserted significantly quicker than the LMA (35.1+/
      15.9 s vs. 56.6+/-42.5 s; mean+/-SD). Insertion of the LT was successful within 1
      attempt in 90% and within 2 or 3 attempts in another 4% of patients for the LT
      compared with 68% and 20% of patients for the LMA, respectively. For the LT the
      initial cuff pressure was significantly lower (75.1+/-16.2 cm H(2)O) and the
      oropharyngeal leak pressure after adjustment of the intra-cuff pressure to 60 cm
      H(2)O was significantly higher (27.2+/-6.9 mbar) compared with the LMA (109.5+/
      25.7 cm H(2)O and 19.9+/-4.0 mbar, respectively). Incidence of postoperative
      laryngeal complications in the LT group (31%) was lower compared with the LMA
      group (54%). CONCLUSION: In anaesthetised non-paralysed patients the LT compares
      favourably to the LMA in terms of ease of insertion and postoperative morbidity.

PMID- 15167951
TI  - [High blood pressure and coronary heart disease. Are there new therapeutic
      options?].
AB  - Besides type 2 diabetes and cigarette smoking arterial hypertension represents
      the most powerful risk factor for the development of coronary artery disease.
      Independent from the existence of coronary artery disease i. e. coronary
      macroangiopathy arterial hypertension leads to hypertension-specific organ
      manifestations such as left ventricular hypertrophy and coronary microangiopathy.
      In the presence of coronary artery disease left ventricular hypertrophy and
      coronary microangiopathy aggravate the ischemic predisposition of the myocardium.
      Thus vascular protection measures should represent an important component of
      antihypertensive treatment. Due to the present state of the art based upon
      randomized clinical studies ACE-inhibitors are first-line antihypertensive
      substances due to their vascular and myocardial protective effects and their few
      side effects. Angiotensin II receptor blockers are not more effective than ACE
      inhibitors in treatment arterial hypertension so far. Calcium channel blockers
      who do not stimulate the sympathetic system such as slow release verapamil and
      amlodipin, beta receptor blockers and diuretics are combination partners, if
      blood pressure cannot be normalized by treatment with ACE-inhibitors only. Since
      statins reduce cardiovascular morbidity and mortality in hypertensive patients
      even with not elevated LDL cholesterol levels, statins represent an important
      component of antihypertensive treatment. An antihypertenive treatment aiming at
      reducing blood pressure only is no more sufficient due to the present state of
      the art.

PMID- 15167950
TI  - [Are all antihypertensive drugs renoprotective?].
AB  - Blood pressure, together with proteinuria, represents one of the most important
      factors in the progression of chronic renal failure (CRF). Antihypertensive
      therapy is beneficial to slow down the progression of a variety of chronic renal
      diseases, no matter what the cause. Intraglomerular hypertension, increased
      glomerular permeability and proteinuria should be identified, since they can be
      treated to prevent or minimize further glomerular injury. But not all
      antihypertensive drugs are equally effective to prevent the progression of CRF.
      Recent large trials indicate that blood pressure lowering obtained by
      intervention in the renin-angiotensin-aldosterone system (RAAS) has an additive
      renoprotective effect in diabetic and nondiabetic renal diseases. In nondiabetic
      patients, the AIPRI and REIN studies support that angiotensin-converting enzyme
      (ACE) inhibitors have a long-term renoprotective effect. The benefits of ACE
      inhibitors can be demonstrated even in patients who are not hypertensive.
      Angiotensin II receptor antagonists are shown to be renoprotective in type 2
      diabetics (RENAAL and IDNT). However, whether these renoprotective effects are
      due to blood pressure reduction or due to the specific pharmacologic RAAS
      blockade is still a matter of debate. This discussion is still open, because the
      reduction in blood pressure levels was lower in patients treated with a drug that
      interferes with the RAAS compared with other antihypertensive regimens. It is
      concluded that both ACE inhibitors and AT II receptor antagonists are lowering
      the intraglomerular pressure independent of any change in systemic blood pressure
      by dilatation of the efferent arteriole of the glomerulus. These additional
      nonpressure-related effects may protect renal function by their antiproteinuric
      effect. In addition, beneficial effect of ACE inhibitors are related to reduction
      of AT II, which has potent proinflammatory effects independent of its hemodynamic
      influences. Other drugs, such as diuretics, beta blockers, and hydralazine, do
      not induce efferent dilatation and, therefore, may be less likely to reverse
      intraglomerular hypertension. For example, hydralazine and nifedipine appear to
      produce prominent afferent or preglomerular arteriolar dilatation. This will
      allow more of the systemic pressure to be transmitted to the glomerulus.
      Therefore, short-acting dihydropyridine calcium channel blockers (CCB) are not
      recommended. By comparison, long-acting dihydropyridines such as diltiazem and
      verapamil are less potent vasodilators and may primarily decrease the resistance
      of the efferent arteriole, similar to the ACE inhibitors. They may have an
      antiproteinuric activity. Yet, there is lack of large prospective randomized
      trials.A beta blocker as antihypertensive agent is indicated as second- or third
      line drug especially in patients with additional cardiovascular disease. Other
      antihypertensive drugs can be added as necessary to achieve the treatment goals
      for arterial hypertension. The use of a diuretic will often be helpful in
      patients who already have renal insufficiency, since fluid overload is an
      important cause of hypertension and may also enhance the effectiveness of drugs
      that interfere with the RAAS. alpha(1)-receptor or sympathetic blockers are
      further possible drugs for combination antihypertensive therapy.

PMID- 15167952
TI  - [OCTAVE and OPERA: discordance in hypertension therapy?].
AB  - While ACE-inhibitors have proven their prognostic benefit in many hypertension
      studies, a new approach has been proposed by inhibiting neutral endopeptidase,
      which degrades natriuretic peptides. The combined inhibition of ACE and
      endopeptidase was named "vasopeptidase-inhibition" and tested in several trial.
      Though effective in lowering blood pressure, a superiority to ACE-inhibitors
      alone could not be shown. A potentially serious side effect was the increased
      incidence of angioneurotic edema, which led to a complete stop in the development
      of this pharmaceutical strategy.

PMID- 15167953
TI  - [Compliance problems in therapy resistant hypertension].
AB  - DEFINITION AND FREQUENCY: Hypertension may be termed refractory, when a
      therapeutic plan that has included nonpharmacologic treatment and the
      prescription of a triple drug combination in adequate doses including a diuretic,
      has failed to lower the blood pressure < 140/90 mmHg. True resistance can only be
      found in 2-5% of all hypertensive patients. CAUSES AND DIAGNOSIS:
      Pseudoresistance to antihypertensive therapy is common and often due to a
      suboptimal drug regime, interactions with other drugs or a secondary form of
      hypertension. It is estimated that in more than two thirds of patients with
      hypertension, poor compliance is at least part of the problem. Poor compliance is
      not easily detected by the physicians, and studies showed that they could not
      predict compliance with any more accuracy than if they were guessing. Factors for
      a poor compliance are lack of patient information about hypertension and its
      treatment, side effects of prescribed drugs, lack of teaching in the self
      measurement of blood pressure and patient's dissatisfaction with the disease.
      Improvement of compliance can be achieved by selecting long-acting drugs or drug
      combinations. Structured teaching programs, as they become part of the Disease
      Management Programs (DMPs) in Germany can improve compliance as well. THERAPY: If
      noncompliance can be excluded, the dosage of antihypertensive drugs should be
      increased to a maximum if tolerated, or combinations of four or more drugs can be
      used, including drugs like minoxidil.

PMID- 15167954
TI  - [Pulse pressure in the therapeutic management of hypertension?].
AB  - Data from the Framingham and several other studies have demonstrated a relatively
      consistent increase of systolic blood pressure over lifetime but a decrease of
      diastolic blood pressure after the age of 50-60 years-resulting in an increase of
      pulse pressure (PP). Epidemiologic studies in the past 10-15 years have stressed
      the importance of PP as an independent risk factor for cardiovascular morbidity
      and mortality, especially myocardial infarction and congestive heart failure.A
      wide clinic PP (60-65 mmHg) has been shown to be a marker of increased arterial
      stiffness and an elevated cardiovascular morbidity. PP is determined by combined
      hemodynamic cardiac (ventricular ejection) and arterial factors, like arterial
      stiffness as well as the timing and intensity of wave reflections. Recent careful
      measurements have suggested that PP is transmitted much deeper into the
      microcirculation, which is strongly influenced by aging, hypertension, diabetes,
      and renal insufficiency (endothelial dysfunction, eutrophic and hypertrophic
      remodeling, progressive loss of microvessels). Antihypertensive drugs may improve
      vascular compliance and the alterations of microvascular architecture by reducing
      blood pressure, relaxing vascular smooth muscle, or promoting long-term effects
      on extracellular matrix, collagen, vascular smooth muscle, and cardiomyocyte
      growth and remodeling.Diuretics, beta blockers, long-acting calcium channel
      blockers, angiotensin-converting enzyme (ACE) inhibitors and angiotensin I
      (AT(1)) receptor antagonists were critically discussed in relation to their
      influence on vascular compliance, endothelial dysfunction, the remodeling
      process, PP, and cardiovascular morbidity and mortality. The vascular protective
      action of some (especially AT(1) antagonists, ACE inhibitors, calcium channel
      blockers) but not all (beta blockers) may contribute to improve the outcome of
      hypertensive patients, although this is presently unproven.

PMID- 15167955
TI  - Oral antidiabetic therapy in patients with heart disease. A cardiologic
      standpoint.
AB  - Five types of oral antihyperglycemic drugs are currently approved for the
      treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones, and
      alpha-glucosidase inhibitors. The cardiovascular effects of the most commonly
      used antidiabetic drugs in these groups are briefly reported, in an attempt to
      improve knowledge and awareness regarding their influences and potential risks
      when treating patients with coronary artery disease (CAD). Regarding biguanides,
      gastrointestinal disturbances such as diarrhea are frequent, and the intestinal
      absorption of group B vitamins and especially folate is impaired during chronic
      therapy. This deficiency may lead to increased plasma homocysteine levels which,
      in turn, accelerate the progression of vascular disease due to adverse effects on
      platelets, clotting factors, and endothelium. The existence of a graded
      association between homocysteine levels and overall mortality in patients with
      CAD is well established. In addition, metformin may lead to lethal lactic
      acidosis, especially in patients with clinical conditions that predispose to this
      complication, such as heart failure or recent myocardial infarction.
      Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they
      may prevent the opening of the ATP-dependent potassium channels, impeding the
      necessary hyperpolarization that protects the cell by blocking calcium influx.
      Meglitinides may exert similar effects, due to their analogous mechanism of
      action. During treatment with glitazones, edema has been reported in 5% of
      patients, and these drugs are contraindicated in diabetics with NYHA class III or
      IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on
      morbidity and mortality rates and on diabetic micro- and macrovascular
      complications are yet unknown. The combined sulfonylurea/metformin therapy
      reveals additive effects on mortality. It is concluded that(1) four of the five
      oral antidiabetic drug groups present proven or potential cardiac hazards;(2)
      these hazards are not mere "side effects", but are deeply rooted in the drugs'
      mechanism of action;(3) current data indicate that the combined
      glibenclamide/metformin therapy seems to present special risk and should be
      avoided in the long-term management of type 2 diabetics with proven CAD; and(4)
      customized antihyperglycemic pharmacological approaches should be investigated
      for optimal treatment of diabetic patients with heart disease.

PMID- 15167956
TI  - Relationship between the degree of intracellular magnesium deficiency and the
      frequency of chest pain in women with variant angina.
AB  - OBJECTIVES: This study sought to clarify the relationship between the degree of
      intracellular magnesium deficiency and the frequency of anginal attacks in women
      with variant angina. PATIENTS AND METHODS: We evaluated the intracellular and
      extracellular magnesium status of twelve women with variant angina: group A (> or
      = 4 attacks/week, n = 5) and group B (< 4 attacks/week, n = 7). Magnesium levels
      were determined in serum, urine, and erythrocytes, and the 24-h magnesium
      retention rate was calculated by magnesium loading test. RESULTS: Group A showed
      a higher 24-h magnesium retention rate (58.2 +/- 9.1% vs. 31.3 +/- 4.4%; p <
      0.01) and a lower intracellular concentration of magnesium in erythrocytes than
      group B (3.1 +/- 1.1 vs. 5.0 +/- 0.8 fg/cell; p < 0.05), demonstrating the
      presence of magnesium deficiency in group A. The 24-h magnesium retention rate
      and intracellular concentrations of magnesium in erythrocytes correlated well
      with the activity of variant angina (r = 0.61, p < 0.01; and r = -0.74, p < 0.01,
      respectively) for these patients. CONCLUSION: This study demonstrates that the
      degree of intracellular magnesium deficiency in women with variant angina is
      closely related to the frequency of chest pain.

PMID- 15167957
TI  - Patients operated for tetralogy of fallot and with non-sustained ventricular
      tachycardia have reduced heart rate variability.
AB  - BACKGROUND: To study heart rate variability (HRV) in patients operated for
      tetralogy of Fallot (ToF) and to identify any correlation between HRV and
      ventricular tachycardia (VT). PATIENTS AND METHODS: We studied HRV in 23
      consecutive patients operated for ToF (mean age 14 +/- 6.6 years; mean follow-up
      10.6 +/- 5.2 years). Seven patients had non-sustained VT on Holter monitoring.
      Two control groups were included: 18 healthy subjects and 15 patients operated
      for other congenital heart disease. There were no differences in age, age at
      surgery (in the operated groups), follow-up, and mean heart rate between the
      three groups. Four time and four frequency domain indices were calculated: mean
      duration of RR intervals, standard deviation of all RR intervals (SD), square
      root of the mean squared differences of successive RR intervals (r-MSSD), percent
      of differences between adjacent RR intervals (pNN50), total power (TP), low
      frequency (LF), high frequency (HF), and LF/HF ratio. RESULTS: HRV indices were
      identical in the two control groups but were significantly reduced in patients
      with ToF. Within the patients who had been operated on for ToF, HRV indices were
      significantly lower in the seven with non-sustained VT than in those without
      arrhythmias: SD (95 +/- 15 vs. 135 +/- 54 ms; p = 0.01), r-MSSD (26 +/- 9 vs. 45
      +/- 20 ms; p = 0.03), pNN50 (4.4 +/- 3.4 vs. 16.5 +/- 12.5%; p = 0.001) and HF
      (111 +/- 97 vs. 352 +/- 291 ms(2); p = 0.009). Using stepwise multivariate
      regression analysis, pNN50, age at surgery, degree of pulmonary regurgitation and
      higher right/left ventricular ratio were independent predictive variables for VT
      (p < 0.0001; r(2) = 0.85). CONCLUSIONS: ToF patients, particularly those with
      ventricular arrhythmias, have significant impairment of sympatho-vagal balance,
      characterized by a reduction of vagal drive.

PMID- 15167958
TI  - [Impact of smoking on the results of coronary artery bypass surgery].
AB  - BACKGROUND AND PURPOSE: The proportion of patients undergoing coronary artery
      bypass surgery (CABG) with a history of smoking is increasing. The aim of this
      study was to examine the effect of smoking on outcomes following CABG. PATIENTS
      AND METHODS: 6,367 consecutive patients who underwent CABG between April 1997 and
      March 2003 were analyzed retrospectively. Logistic regression was used to risk
      adjust inhospital outcomes, while Cox proportional hazards analysis was used to
      risk-adjust Kaplan-Meier survival curves. Outcomes were adjusted for variables
      suggested by the American Heart Association and the American College of
      Cardiology. RESULTS: 947 patients (14.9%) were current smokers (smoking within 1
      month of surgery), while 3,857 (60.6%) were ex-smokers and 1,563 (24.5%)
      nonsmokers. After adjusting for differences in case-mix, current smokers were
      more likely to develop chest infections (p < 0.001), atelectasis (p < 0.001), and
      require ventilation > 48 h (p = 0.003). Current smokers were also more likely to
      stay in intensive care for > 3 days (p < 0.001). There was no association between
      smoking status and in-hospital mortality. Ex-smokers were not associated with
      excess mortality (p = 0.11), while current smokers had significantly increased
      mortality during follow-up (p = 0.029). CONCLUSION: Current smokers are
      associated with increased respiratory complications, and prolonged stay on
      intensive care. Although not associated with in-hospital mortality, there appears
      to be a significant increase in mortality in smokers during a 4-year follow-up
      period. Patients should be encouraged to stop smoking to maximize the long-term
      benefits of CABG.

PMID- 15167959
TI  - [Infection sources in HNO- and jawbone regions in patients before valve
      replacement surgery].
AB  - BACKGROUND: Prosthetic valve endocarditis is a life-threatening complication
      after valve replacement surgery. Therefore, it is common to perform a screening
      for potential sources of infection before surgery in order to be able to do a
      prophylactic treatment. PATIENTS AND METHOD: The incidence of potential
      infectious sources of bacteremia in the dental, jaw and nasopharyngeal area was
      evaluated in 92 patients going to have valve replacement surgery. Screening
      examinations were an X-ray of the paranasal sinuses and a panoramic radiograph of
      the dental arch. Chronic apical periodontitis, cysts and remaining radices were
      counted as dental sources. Each shadow in the paranasal sinuses X-ray was seen as
      pathological and was further investigated by an otorhinolaryngologist. RESULTS: A
      potential infectious source was found in 49 patients. 42 patients had a dental
      infectious source with need for treatment. 19 patients showed a pathologic sinus
      X-ray (three aspergillomas, three sinusitis, the others had a chronic polyposis
      with no need for treatment). Twelve patients had dental as well as sinusoidal
      sources. Erythrocyte sedimentation rate did not refer to the appearance of
      infectious sources. Patients going to have a mitral valve replacement had most
      dental sources (61%), 47% of the patients with planned aortic valve replacement,
      50% of the patients planned to get more than one heart valve replaced, 50% of the
      patients getting mitral valve replacement and CABG and 40% of the patients
      waiting for aortic valve replacement and CABG had dental foci. CONCLUSION:
      Screening for infectious foci before valve replacement surgery diagnosed foci in
      a high percentage of the patients. Nevertheless current data concerning whether a
      prophylactic treatment may reduce the incidence of prosthetic valve endocarditis
      are conflicting.

PMID- 15167960
TI  - [Functional aspects of endothelial phenotypes in the human heart.
      Immunohistochemical study for the evaluation of endothelial adhesion molecule
      expression].
AB  - BACKGROUND AND PURPOSE: The endothelial lining is a confluent monolayer of thin
      and rhomboid-shaped cells, that covers the inner surface of all blood vessels.
      However, the essential role of endothelial cells in all aspects of cardiovascular
      physiology, homeostasis and the pathogenesis of most cardiovascular diseases no
      longer remains controversial. Although much evidence has been achieved regarding
      the molecular functioning of transcription factors and regulatory proteins, many
      questions on endothelial heterogeneity with regard to function and morphology at
      various vascular sites remain unanswered. In this study, an immunohistochemical
      map of endothelial adhesion molecule expression at various vascular sites of the
      healthy human heart is created. Using this map, the authors examined whether
      expression patterns are distinctive by their molecular function at their site of
      origin. Furthermore, immunohistochemical findings were associated with the
      clinical situation. MATERIAL AND METHODS: Tissue samples from eleven different
      vascular locations of healthy human hearts were analyzed using
      immunohistochemistry. Endothelial adhesion molecules of the selectin, immune
      globulin supergen, and integrin families, some complementary cellular adhesion
      molecules, and the von Willebrand factor were analyzed. RESULTS: Endothelial
      adhesion molecule expressions were found to be characteristic of all vascular
      sites investigated. Thus, molecules involved in inflammatory reactions were
      predominantly expressed within the myocardial microvasculature, whereas molecules
      serving for endothelial anchorage toward extracellular matrix components could be
      observed especially on endocardial and valvular surfaces. Apart from that, a
      parallel expression of immunologically relevant as well as integrin molecules
      were found to be characteristic of coronary arteries. CONCLUSION: To the authors'
      knowledge, this is the first report on site-specific expression characteristics
      for all vascular sites of the human heart. Thus, our data provide important novel
      information, which ultimately will help to bring some light into the field of
      cardiac physiology.

PMID- 15167961
TI  - [Protective effects of a delta-opioid-receptor agonist and an oxygen radical
      scavenger on postischemic hearts].
AB  - BACKGROUND AND PURPOSE: The cardioprotective effects of delta-opioid receptor
      agonists is mediated-at least in part-via oxygen radicals. Mannitol that is used
      in cardiac surgery because of its osmotic properties exerts its beneficial
      effects on stunned myocardium via scavenging hydroxyl radicals. The effects of a
      delta-opioid receptor agonist (D-Ala2-D-Leu5-Enkephalin [DADLE]), the radical
      scavenger mannitol and their combination on postischemic dysfunction in rabbit
      hearts were investigated. METHODS: Isolated, blood-perfused rabbit hearts were
      subjected to a 20-min global, normothermic, no-flow ischemia that was followed by
      a 60-min reperfusion. Systolic and diastolic ventricular function as well as
      coronary blood flow (CBF) were assessed. The hearts were assigned to one of four
      groups: 1. placebo (n = 6); 2. DADLE (n = 8; 430 nM); 3. mannitol (n = 7; 8.6
      mM); 4. DADLE + mannitol (n = 7). RESULTS: Ischemic contracture in the DADLE and
      the mannitol group was significantly smaller compared with the placebo group.
      Contracture was smallest in the DADLE + mannitol group. The postischemic function
      in the placebo group was drastically reduced (p < 0.05), while it was best
      preserved in the DADLE + mannitol group. CBF and MVO(2) were changed similarly in
      all groups (n. s.). The external efficiency was significantly higher in the
      groups with DADLE and/or mannitol than in the placebo group. Both DADLE and
      mannitol exhibit cardioprotective properties. Combination of both substances
      exerts an additive, positive effect on the ischemic contracture. Noteworthy, the
      protective effects of DADLE during reperfusion were not antagonized by the oxygen
      radical scavenger mannitol. On the other hand, DADLE + mannitol did not augment
      the protective effects of the single substances during reperfusion, except for
      the isovolumic LVP(max). CONCLUSION: Both substances improve the postischemic
      systolic and diastolic function and the relation between cardiac work and oxygen
      needed for this work. Thus, both substances offer promising properties in the
      clinic.

PMID- 15167963
TI  - Arrhythmia risk stratification with regard to prophylactic implantable
      defibrillator therapy in patients with dilated cardiomyopathy. Results of MACAS,
      DEFINITE, and SCD-HeFT.
AB  - To date, generally accepted indications for prophylactic defibrillator
      implantation in patients with dilated cardiomyopathy do not exist. Recently, the
      Marburg Cardiomyopathy Study (MACAS) revealed left ventricular ejection fraction
      to be the only significant arrhythmia risk predictor in a relatively large
      patient population with dilated cardiomyopathy. Meanwhile, the preliminary
      results of two prospective randomized trials evaluating prophylactic
      defibrillator therapy in dilated cardiomyopathy have been reported. The
      Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study
      (DEFINITE) randomized 458 patients with a history of symptomatic heart failure, a
      left ventricular ejection fraction < or = 35% and arrhythmias on Holter to an ICD
      versus no ICD. As a result, ICD therapy was associated with a significant
      reduction of arrhythmic deaths, which failed to result in a significant decrease
      in total mortality due to an insufficient number of patients in DEFINITE. The
      Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) was a three-arm study
      comparing placebo to amiodarone to prophylactic ICD therapy in a total of 2,521
      patients with ischemic cardiomyopathy (51%) or nonischemic dilated cardiomyopathy
      (49%). All patients in SCD-HeFT had a left ventricular ejection fraction inverted
      exclamation mark U 35% despite optimized medical heart failure therapy. SCD-HeFT
      showed a significant reduction of total mortality in the ICD group, whereas
      amiodarone did not improve survival.

PMID- 15167962
TI  - [Cultivation of human cells on polymer covered biomaterial--a new concept to
      improve the implant characteristics. Results of an in-vitro-investigation].
AB  - BACKGROUND AND PURPOSE: Calcific degeneration with the resulting need for
      operative replacement remains the major drawback of bioprostheses. Previous
      studies have shown that cellular surface seeding decreases calcium uptake in
      vitro and in vivo, but complete coverage remains difficult to achieve. A new
      approach is presented, masking glutaraldehyde residues with a covalently bound
      polymer layer thus facilitating cell seeding. The aim of this study was to
      evaluate different polymers for their ability to promote surface cell adhesion
      and formation of complete monolayers. MATERIAL AND METHODS: Ten ultrathin
      polymers, covalently bound to glass and exhibiting different physicochemical
      characteristics (thickness, molecular weight, hydrophilic properties, electrical
      charge) were seeded with human endothelial cells. Four of the ten polymers were
      also seeded with fibroblasts. As a reference, both cell types were seeded on
      glass surface. Quality of cell growth and coverage was evaluated by light and
      scanning electron microscopy. RESULTS: Five of ten polymers and glass exhibited
      excellent growth and complete surface coverage after 2 weeks, two allowed less
      cell adherence than glass reference, and three showed only poor cellular growth
      without adherence. Scanning electron microscopy demonstrated an intact monolayer
      for the five polymers with excellent cell coverage. Fibroblasts grew well on
      glass but not on the four tested polymers. No correlation was found between
      molecular weight, thickness, hydrophilic or charge characteristics of the
      polymers. CONCLUSION: Several ultrathin polymers, seeded with human endothelial
      cells, permit complete monolayer formation, but without any apparent correlation
      to physicochemical characteristics. Polymers covalently bound to biologic tissue
      appear as a promising approach to prevent calcific degeneration of bioprostheses.

PMID- 15167964
TI  - Image of the month. Cardiac arrest due to severe hyperkalemia.

PMID- 15167966
TI  - Detection of histidine decarboxylase mRNA in human vascular smooth muscle and
      endothelial cells.
AB  - OBJECTIVE: The objective of this study was to investigate histamine synthesis
      capability of human vascular smooth muscle and endothelial cells by detecting
      histidine decarboxylase (HDC) mRNA. METHODS: HDC catalyzes exclusively the
      formation of histamine in mammalian cells. Experiments utilizing nested reverse
      transcription-polymerase chain reaction (nRT-PCR) were conducted to detect the
      presence of HDC mRNA. Human aortic smooth muscle cells (HAoSMC) and human aortic
      endothelial cells (HAEC) were cultured and RNA was extracted and amplified using
      two sets of HDC-specific primers. Rat liver and kidney RNA were isolated and
      amplified to serve as positive and negative controls, respectively. RESULTS: Gel
      electrophoresis of HAoSMC, HAEC and liver mRNA revealed bands coinciding with an
      expected product size of 440 base pairs. Sequence analysis revealed that the
      observed bands were the appropriate HDC amplicons. CONCLUSIONS: These findings
      are the first to indicate the presence of HDC mRNA in vascular smooth muscle
      cells and confirm the presence of HDC mRNA in endothelial cells which is
      consistent with an ability of these cell types to synthesize histamine in the
      vascular wall.

PMID- 15167968
TI  - Polyclonal anti-histamine H2 receptor antibodies detect differential expression
      of H2 receptor protein in primary vascular cell types.
AB  - OBJECTIVE AND DESIGN: One of the factors defining cellular response might be the
      distribution and density of receptor subtypes on cell membranes. It was our aim
      to quantify and compare histamine H2 receptor expression in primary vascular cell
      types. We have therefore generated antibodies directed against the second extra
      cellular loop of the H2 receptor. METHODS: The specificity of polyclonal anti-H2
      receptor antibodies designed for this purpose was examined by Western blot
      analysis and immunohistochemistry. H2 receptor expression was quantified by
      ELISA. Regulation of H2 receptor gene expression was analyzed by competitive RT
      PCR. RESULTS: Our results indicate that the polyclonal antibodies specifically
      interact with the histamine H2 receptor. Furthermore, utilizing these antibodies
      we were able to show significant differences in H2 receptor levels in human
      umbilical arterial and vein endothelial cells as well as smooth muscle cells.
      CONCLUSIONS: We conclude that the antibodies generated against the extra-cellular
      domain of the H2 receptor are specific and can be utilized to detect and quantify
      H2 receptor expression. Furthermore, the significant differences in H2 receptor
      expression in different vascular cell types might play a critical role in
      defining histamine induced cellular responses during physiological or
      pathophysiological processes.

PMID- 15167967
TI  - Induction of cyclooxygenase-1 in cultured synovial cells isolated from rheumatoid
      arthritis patients.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to confirm the involvement of
      cyclooxygenase (COX)-1 in rheumatoid arthritis (RA). MATERIALS AND SUBJECTS:
      Synovial cells isolated from arthritic patients were cultured primarily and
      consecutively for 8 passages. TREATMENT: The cultured synovial cells were
      incubated with 10 ng/ml of interleukin-1alpha (IL-1alpha) for 6 h. METHODS: The
      effects of either COX-1 or COX-2 selective inhibitor on prostaglandin E2 (PGE2)
      production was estimated by enzyme-linked immunosorbent assay (ELISA) and the
      expression of COX-1 and COX-2 were determined by Western blotting and
      immunocytochemistry. RESULTS: IL-1alpha-induced PGE2 production in synovial cells
      isolated from RA in primary culture was inhibited by mofezolac, a selective
      inhibitor of COX-1, as well as NS-398, a specific inhibitor of COX-2. The similar
      inhibitory patterns were obtained in the RA-derived synovial cells within 3
      passages. However, COX activity in the RA-derived synovial cells after 5 passages
      was inhibited by NS-398, but not by mofezolac. In contrast, COX activity in
      primary and consecutively cultured synovial cells isolated from osteoarthritis
      (OA) or normal arthritis was inhibited by NS-398, but not by mofezolac. Western
      blot and immunocytochemical analyses of COX-1 and COX-2 in the synovial cells
      isolated from RA patients within 3 passages showed an induction in both COX-1 and
      COX-2 expression by IL-1alpha. The induction of both COX-1 and COX-2 was
      inhibited by dexamethasone. CONCLUSIONS: These experiments demonstrate COX-1
      induction in synovial cells isolated from RA patients, suggesting that COX-1 is
      involved in the progression of RA.

PMID- 15167969
TI  - Human neutrophil defensins and secretory leukocyte proteinase inhibitor in
      squamous metaplastic epithelium of bronchial airways.
AB  - OBJECTIVE: The aim of this study was to analyze a possible contribution of human
      neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the
      induction of airway epithelial changes such as squamous cell metaplasia.
      MATERIALS AND METHODS: The presence of these molecules and the number of
      proliferating (Ki-67-positive) epithelial cells was analyzed by
      immunohistochemistry in bronchial epithelium from subjects with (n = 15) or
      without (n = 14) chronic obstructive pulmonary disease (COPD). RESULTS: Our data
      demonstrate higher numbers of defensin-positive (p = 0.0001), elastase-positive
      (p = 0.0001) and Ki-67-positive (p = 0.0001) cells in areas with squamous cell
      metaplasia as compared to areas with intact or damaged epithelium, while the
      reverse was observed for SLPI expression (p = 0.002). No differences were
      observed between subjects with or without COPD, nor between current smokers and
      those that had stopped smoking. CONCLUSIONS: These data are in line with a role
      of defensins in the hyperproliferative phenotype of squamous metaplastic lesions
      in the airways. This role does not seem to be restricted to patients with COPD.

PMID- 15167970
TI  - Enhancement of nitric oxide and proteoglycan synthesis due to cyclic tensile
      strain loaded on chondrocytes attached to fibronectin.
AB  - OBJECTIVE: Mechanical stress is an essential factor in the pathogenesis of
      osteoarthrosis. We sought to determine whether the strain-mediated alteration in
      proteoglycan (PG) synthesis was modulated by nitric oxide (NO) synthesis.
      METHODS: Cyclic tensile strain was applied to bovine articular chondrocytes. PG
      and NO synthesis were determined by [35S] sulfate incorporation and
      chemiluminescence analysis, respectively. To determine the expression of
      inducible NO synthase (iNOS), quantitative RT-PCR was used. RESULTS: Enhanced PG
      and NO synthesis were evident when cyclic tensile strain was applied to
      chondrocytes seeded on fibronectin-coated plates. When NO production was
      inhibited, PG synthesis was further enhanced. CONCLUSIONS: Cyclic tensile strain
      loaded on the chondrocytes enhanced NO synthesis and this enhanced NO inhibited
      PG synthesis.

PMID- 15167972
TI  - An immunoglobulin agent (IVIG) inhibits NF-kappaB activation in cultured
      endothelial cells of coronary arteries in vitro.
AB  - OBJECTIVE: Kawasaki disease (KD) is an acute febrile vasculitis of unknown
      etiology that may lead to cardiovascular disorders. High-dose intravenous
      immunoglobulin (IVIG) therapy is well established as a standard therapy for KD.
      Tumor necrosis factor-alpha (TNF-alpha) is responsible for the pathogenesis of
      acute KD. We examined whether or not IVIG inhibits TNF-alpha-induced activation
      of transcription factor NF-kappaB, a factor that is essential for the expression
      of proinflammatory cytokines, in human coronary artery endothelial cells (CAEC).
      METHODS: The inhibitory effect of IVIG on NF-kappaB activation induced by TNF
      alpha was evaluated by Western blot analysis and ELISA. Moreover, the inhibitory
      effects of IVIG on IkappaBalpha degradation, interleukin-6 (IL-6) production, and
      E-selectin expression induced by TNF-alpha were evaluated by Western blot
      analysis, ELISA, and flow cytometry, respectively. RESULTS: Western blot analysis
      and ELISA demonstrated that IVIG inhibits NF-kappaB activation induced by TNF
      alpha in CAEC. Moreover, IVIG inhibited IkappaBalpha degradation, IL-6
      production, and E-selectin expression induced by TNF-alpha in CAEC. CONCLUSION:
      The data suggest that IVIG inhibits NF-kappaB activation induced by TNF-alpha in
      CAEC, thereby possibly modulating IL-6 production and E-selectin expression.

PMID- 15167971
TI  - Activation of histamine H1-receptor enhances neurotrophic factor secretion from
      cultured astrocytes.
AB  - OBJECTIVE: Histamine stimulates nerve growth factor (NGF) secretion from cultured
      astrocytes. Histamine H(1)-receptor antagonists completely block its effect. In
      the present study, we determined the involvement of histamine-receptor subtypes
      in this process. MATERIALS AND METHODS: Radioligand-binding assay was used to
      establish the presence of histamine H(1)- and H(2)-receptors on new-born rat
      cortical astrocytes in primary culture. Histamine H(1)-, H(2)- and H(3)/H(4)
      receptor ligands, and highly selective protein kinase C (PKC) inhibitor were used
      to influence NGF secretion from cultured astrocytes. NGF, released into the
      culture medium, was measured by NGF-ELISA. RESULTS: Histamine H(1)-receptor
      agonists (histamine, selected histaprodifens) increased the secretion of NGF from
      cultured astrocytes in a concentration-dependent manner. H(1)-receptor
      antagonists/inverse agonists (mepyramine, triprolidine) and PKC inhibitor
      completely blocked the effect of histamine. Histamine H(2)- and H(3)-receptor
      agonists did not enhance NGF secretion significantly. In addition, H(2)- and
      H(3)/H(4)-receptor antagonists did not diminish histamine-stimulated NGF release.
      CONCLUSIONS: Our results indicate that histamine H(1)-receptor and PKC are
      involved in the signal transduction pathway, responsible for histamine-stimulated
      NGF secretion from cultured astrocytes.

PMID- 15167973
TI  - Involvement of the neuropeptide substance P in lung inflammation induced by
      hepatic ischemia/reperfusion.
AB  - OBJECTIVE AND DESIGN: The purpose of this study was to examine the potential role
      of substance P in accumulation of neutrophils in the lung following hepatic
      ischemia/reperfusion. MATERIALS AND METHODS: Male C57BL/6 mice (8-10 weeks of
      age) were subjected to either sham surgery, partial hepatic ischemia with or
      without reperfusion, or intratracheal administration of saline or 1 ng substance
      P. Lung neutrophil accumulation was assessed by tissue content of
      myeloperoxidase. Activation of the transcription factor, NF-kappaB, was
      determined by electrophoretic mobility shift assay. Levels of substance P and
      macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid
      was measured using enzyme-linked immunosorbent assays. RESULTS: Significant
      pulmonary neutrophil accumulation was observed just prior to hepatic reperfusion
      in association with increased BAL levels of substance P. Intratracheal
      administration of substance P resulted in a similar pattern of neutrophil
      accumulation which was associated with activation of NF-kappaB and increased BAL
      levels of the chemokine, MIP-2. CONCLUSIONS: The data suggest that hepatic
      ischemia causes substance P release in the lung which activates NF-kappaB leading
      to the production of MIP-2 and accumulation of neutrophils.

PMID- 15167974
TI  - The inhibition of retinal inducible nitric oxide synthase overexpression and the
      attenuation of experimental uveitis by anti-inflammatory drugs in rats.
AB  - OBJECTIVE AND DESIGN: The effect of a steroid and a non-steroid anti-inflammatory
      drug on the inducible nitric oxide synthase (NOS II) in rats suffering from
      lipopolysaccharide (LPS)-induced uveoretinitis was studied. TREATMENTS: Rats were
      injected with LPS to induce uveitis and divided into three groups: treated with
      LPS only, LPS + dexamethasone and LPS + indomethacin, respectively. METHODS:
      Retinal, peritoneal macrophages and white blood cells were isolated. The activity
      and the expression of NOS II were followed by citrulline formation and Western
      blotting, respectively. Phagocytosis of bacteria was also measured. RESULTS: The
      best induction of NOS II was achieved by the intravitreal administration of LPS.
      Dexamethasone and indomethacin significantly decreased the activity and the
      expression of inducible nitric oxide synthase in retinal tissue, peritoneal
      macrophages and white blood cells. LPS treatment also increased phagocytosis and
      neither dexamethasone nor indomethacin reversed this effect. CONCLUSIONS: The
      beneficial effects of these drugs in experimental uveitis are mediated, at least
      partly, by their inhibitory effect on NOS II induction.

PMID- 15167975
TI  - Colour vision can contribute to fast corrections of arm movements.
AB  - Can chromatic information be used for the fast on-line control of action? In
      order to find out we asked subjects to tap a red square as quickly as possible.
      In half of the trials the red square's position changed as soon as the subject's
      hand started to move. We examined how quickly subjects could adjust their
      movements to this change. In half of the trials there was also a green square of
      the same luminance as the red one. If there was a green square, and the red
      square's position changed, the change consisted of the two squares exchanging
      places, so that all that really changed was the squares' colours. In such cases
      subjects could not have adjusted their movements without having analysed the
      colour. Nevertheless, subjects could respond adequately within as little as 120
      ms. This was even so if the squares' luminances changed considerably at the
      moment that the subject's hand started to move. Thus, chromatic information can
      be used for the fast on-line control of action.

PMID- 15167976
TI  - The strategies to regulate and to modulate the propulsive forces during gait
      initiation in lower limb amputees.
AB  - We used the framework of motor program adaptability to examine how unilateral
      above-knee (AK) or below-knee (BK) amputee subjects organize the global and local
      biomechanical processes of generation of the propulsive forces during gait
      initiation to overcome the segmental and neuro-muscular asymmetry. The
      organization of the global biomechanical process refers to the kinematics
      behavior of the couple center of foot pressure (CoP) and center of mass (CoM);
      the organization of the local biomechanical process refers to the propulsive
      forces generated by the prosthetic or intact limb during the anticipatory
      postural adjustment phase and the step execution phase. Specifically, we
      examined: i) the strategy to regulate the progression velocity, i.e., to maintain
      it comparably when the leading limb changed from the prosthetic limb to the
      intact limb; and ii) the strategy to modulate the progression velocity, i.e., to
      increase it when gait was initiated with the prosthetic limb vs. intact limb. The
      kinematics of the CoM and CoP in the amputees showed the same global
      biomechanical organization that is typically observed in able-bodied subjects,
      i.e., the production of the forward disequilibrium torque was obtained by a
      backward shift of the CoP, followed by a forward acceleration of the CoM.
      However, gait initiation was achieved by using a different local strategy
      depending on which limb was used to initiate the step. For the regulation of the
      CoM progression velocity, when the gait was initiated with the intact limb, the
      slope of the progression velocity during the anticipatory postural adjustment
      phase (APA) was steeper and lasted longer, the step execution duration was
      shorter, and the variation of the CoM speed was lower. In other words, to
      regulate the speed of progression, the amputee subjects controlled the spatial
      and temporal parameters of the propulsive forces. In the modulation of the CoM
      progression velocity, when the gait was initiated with the intact limb, the
      amputees controlled only the intensity of the propulsive forces during both the
      APA and step execution phases. In contrast, when the gait was initiated with the
      prosthetic limb, the modulation resulted mainly from the propulsive forces
      generated during the step execution phase. These different strategies are
      discussed in terms of the subject's capacity to adapt the motor program for gait
      initiation to new constraints.

PMID- 15167978
TI  - Internally generated and externally triggered actions are physically distinct and
      independently controlled.
AB  - In everyday life we must constantly balance our intentions to act in a certain
      way with reactions that are imposed upon us by the outside world. Recent
      neuroimaging studies have examined these classes of movement separately but
      despite the fundamental requirement for us to efficiently organize our internally
      generated and externally triggered actions, few studies have examined the
      relationship between these two classes of movement. We measured EMG activity in
      the right first dorsal interosseous while subjects performed right index finger
      key presses either in an internally generated condition or an externally
      triggered condition. In addition, in an attempt to probe the relationship between
      the processing underlying these two types of action, we examined the effect on
      reaction time (RT) and EMG activity in a third "truncation" condition in which
      subjects were forced to switch from an intentional (internally generated) mode of
      response production to an externally triggered mode. Results indicated
      significantly greater muscle activation for actions that were internally
      generated as compared to externally triggered. Truncation caused responses to be
      delayed by, on average, 54.7 ms as compared with simple externally triggered
      responses, suggesting that the motor system cannot take advantage of preexisting
      levels of preparation when switching between internally generated and externally
      triggered actions. Interestingly, the unique EMG signatures of internally
      generated and externally triggered actions were preserved in truncation. Thus,
      subjects switched between the two types of action rather than simply modifying an
      ongoing action. The results provide peripheral physiological support for previous
      neuroimaging work suggesting that internally generated actions are preceded by
      greater levels of preparation than externally triggered actions. The present
      findings also raise the interesting possibility that the motor system processes
      these two classes of action separately even though the motor output required is
      the same.

PMID- 15167977
TI  - When practice leads to co-articulation: the evolution of geometrically defined
      movement primitives.
AB  - The skilled generation of motor sequences involves the appropriate choice,
      ordering and timing of a sequence of simple, stereotyped movement elements.
      Nevertheless, a given movement element within a well-rehearsed sequence can be
      modified through interaction with its neighboring elements (co-articulation). We
      show that extensive training on a sequence of planar hand trajectories passing
      through several targets resulted in the co-articulation of movement components,
      and in the formation of new movement elements (primitives). Reduction in movement
      duration was accompanied by the gradual replacement of straight trajectories by
      longer curved ones, the latter affording the maximization of movement smoothness.
      Surprisingly, the curved trajectories were generated even when new target
      configurations were introduced, i.e., when target distances were scaled, movement
      direction reversed or when different start and end positions were used,
      indicating the acquisition of geometrically defined movement elements. However,
      the new trajectories were not shared by the untrained hand. Altogether, our
      results suggest that novel movement elements can be acquired through extensive
      training in adults.

PMID- 15167979
TI  - Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area
      induces reinstatement of cocaine-seeking behaviour in rats.
AB  - RATIONALE: The mesocorticolimbic dopamine (DA) system is critically involved in
      mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a
      neuropeptide that significantly interacts with the mesocorticolimbic system,
      therefore suggesting a possible role for the SP system in the mediation of
      relapse. OBJECTIVES: This study examined the effects of injections of the SP
      analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of
      cocaine-seeking behaviour, as well as on locomotor activity in rats.
      Additionally, this study examined whether these effects are DA-dependent.
      METHODS: Rats were trained to self-administer cocaine for 15 days followed by 15
      days of extinction. Reinstatement of cocaine-seeking behaviour was then measured
      in response to bilateral intra-VTA microinjections of DiMe-C7 (0, 0.1, 0.5 and
      2.5 microg). In a separate group of rats, locomotor activity was measured in
      response to intra-VTA injections of DiMe-C7 (0, 0.5, 1.5 and 3 microg). The
      effects of pre-treatment with DA receptor antagonists on DiMe-C7-induced
      reinstatement and locomotor activity were also examined. Animals were pre-treated
      with the D(1) and D(2) receptor antagonists, SCH23390 and haloperidol (0, 0.01
      and 0.03 mg/kg, IP), respectively, prior to receiving intra-VTA injections of
      DiMe-C7 (0 and 2.5 microg). RESULTS: Infusion of DiMe-C7 into the VTA increased
      locomotor activity and induced reinstatement of cocaine-seeking behaviour. Both
      SCH23390 and haloperidol blocked intra-VTA DiMe-C7-induced locomotor activation.
      In addition, SCH23390 attenuated DiMe-C7-induced reinstatement of cocaine-seeking
      behaviour, while haloperidol had no effect. CONCLUSIONS: These results suggest
      that interactions between SP and the mesocorticolimbic DA system may play a role
      in mediating reinstatement of cocaine-seeking behaviour and that the involvement
      of these interactions in reinstatement are dependent upon D(1) receptor
      mechanisms.

PMID- 15167980
TI  - Anxiolytic-like profile in Wistar, but not Sprague-Dawley rats in the social
      interaction test.
AB  - RATIONALE: The social interaction test is a valuable behavioural model for
      testing anxiolytic drugs in rodents, quantifying the level of social behaviour
      between pairs of rats. OBJECTIVE: The aim of the present study was to assess the
      appropriateness of the social interaction test for use with a Sprague-Dawley rat
      line, because of increasing use of this strain in targeted mutagenesis research.
      METHODS: Sprague-Dawley and Wistar rats received either diazepam or mCPP or were
      exposed to different environmental conditions (lighting, social isolation prior
      testing, habituation, testing-time). General anxiety-related parameters measured
      were: duration of active social contact, frequency of active social contact,
      latency to first contact. Different forms of active social contact were recorded:
      number of crawls, follows and sniffs. Secondly, aversion-induced hippocampal
      serotonin release and serotonin content in brain regions were measured. RESULTS:
      In Wistar rats habituation to the test substantially increased the time of social
      contact, an effect comparable with treatment with diazepam (1 mg/kg), whereas
      changes in the lighting level had less impact. Latency to the first contact
      increased under "anxiety-reducing" conditions, the frequency of contacts did not
      change consistently. Sprague-Dawley rats behaviour did not change under varying
      environmental conditions, and treatment with diazepam had only sedating effects
      at higher doses (5 mg/kg). Anxiogenic doses of mCPP caused reduced social
      interaction in both strains. Serotonin release and serotonin content were higher
      in the anxious Wistar rats. CONCLUSIONS: Different rat strains as well as
      differing test conditions have a major impact on the outcome of this animal test
      for anxiety.

PMID- 15167981
TI  - Discriminative stimulus effects in rats of SR-141716 (rimonabant), a cannabinoid
      CB1 receptor antagonist.
AB  - OBJECTIVE: To examine the discriminative stimulus effects of (i) the cannabinoid
      CB(1) receptor antagonist SR-141716 (SR, 5.6 mg/kg) and vehicle, and (ii) the
      cannabinoid receptor agonist Delta(9)-THC (THC, 1.8 mg/kg) and vehicle using a
      discriminated taste aversion (DTA) procedure. METHODS: Two groups of rats ( n=6)
      were trained to discriminate between these drugs and vehicle in DTA ( t'=20 min).
      The 30-min drinking bout of tap water following drug (SR or THC) treatment was
      followed by an injection of lithium chloride (LiCl, 120 mg/kg) in the
      experimental animals. When offered water after vehicle pretreatment, experimental
      animals subsequently were given IP saline (NaCl, 10 ml/kg). Post-drinking
      treatment for controls ( n=6) was NaCl, irrespective of the pretreatment
      condition (SR, THC or vehicle). Additional water was provided during the
      afternoon (30 min) with no other manipulations. Food was available ad lib at all
      times. When the discriminations were established other doses and drugs were
      examined ( t'=20 min). In testing there were no post-drinking treatments.
      RESULTS: The SR-related analog AM-251 (dose range: 1-5.6 mg/kg) substituted for
      SR, whereas other drugs such as the cannabinoid CB(2) receptor antagonist SR
      144528 (3 and 10 mg/kg), THC (1-10 mg/kg), flumazenil (1-10 mg/kg), naloxone (1
      10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3 mg/kg) did not.
      There was a dose-related attenuation of SR-induced suppression of drinking when
      THC (1.8-10 mg/kg) was given together with SR (5.6 mg/kg). In the THC trained
      rats, SR (1-10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3
      mg/kg) did not substitute for THC. SR (1 mg/kg) attenuated the THC (1.8 mg/kg)
      induced suppression of drinking. Together with 3 mg/kg SR and 1.8 mg/kg THC,
      drinking was roughly equally suppressed in both the experimental group and the
      controls. CONCLUSION: SR-141716 induces a discriminative stimulus complex in DTA
      that shows potential for further examination of cannabinoid receptor antagonism.

PMID- 15167982
TI  - The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on
      spontaneous and cocaine-induced behavior.
AB  - RATIONALE: The contribution of the 5-HT(1A) somato-dendritic autoreceptor
      populations to spontaneous and cocaine-induced locomotion is unclear. OBJECTIVES:
      To use a low dose range of +/-8-hydroxy-2-(di- n-propylamino)tetralin (8-OHDPAT)
      to preferentially stimulate 5-HT(1A) autoreceptors and a medium 8-OHDPAT dose
      range to stimulate both 5-HT(1A) autoreceptors and postsynaptic receptors as
      pretreatments prior to either saline or cocaine. METHODS: In experiment 1, either
      a medium dose of 8-OHDPAT (0.4 mg/kg) or a low dose (0.05 mg/kg) was given as
      pretreatments 20 min before five separate 20-min open-field tests. In experiment
      2, the pretreatments were changed to a low dose range of 8-OHDPAT (0.01-0.05
      mg/kg), with or without WAY 100635 (0.01-0.05 mg/kg). In experiment 3, the 8
      OHDPAT pretreatments (0.01, 0.025 or 0.05 mg/kg) were administered 20 min prior
      to saline or cocaine (10 mg/kg) tests. In experiment 4, a medium dose range (0.2
      0.3 mg/kg) was given 20 min prior to saline or cocaine (10 mg/kg) tests. RESULTS:
      Experiment 1 showed that 8-OHDPAT (0.4 mg/kg) tended to increase locomotor
      activity but that pretreatment with 0.05 mg/kg severely suppressed locomotor
      activity. In experiment 2, 8-OHDPAT in the low dose range inhibited locomotor
      activity and this effect was reversed by co-administration of WAY 100635.
      Experiment 3 showed that the low-dose 8-OHDPAT pretreatment reduced locomotor
      activity in saline but not cocaine tests. In experiment 4, 8-OHDPAT in the medium
      dose range enhanced locomotor activity in cocaine tests. CONCLUSIONS: It is
      suggested that the facilitatory effect of 8-OHDPAT on cocaine-induced locomotor
      stimulation is mediated by inhibition of 5-HT(1A) somato-dendritic autoreceptors.

PMID- 15167983
TI  - ATP priming of macrophage-derived chemokine responses in CHO cells expressing the
      CCR4 receptor.
AB  - The mechanism by which ATP primes for subsequent macrophage-derived chemokine
      (MDC) mediated intracellular calcium (Ca2+(i)) responses at the human CCR4
      receptor stably expressed in Chinese hamster ovary (CHO) cells was investigated.
      MDC alone was unable to elicit a Ca2+(i) response, but pre-stimulation of cells
      with ATP enabled a subsequent MDC-mediated Ca2+(i) response with a pEC50 of
      8.66+/-0.16. The maximal response elicited by MDC was dependent upon the
      concentration of ATP used to prime, but the pEC50 was stable at all ATP
      concentrations tested. Pertussis toxin pre-treatment did not effect the ATP
      response, but abolished that to MDC, demonstrating that priming with ATP did not
      alter G protein-coupling specificity of the CCR4 receptor. Ionomycin and
      thapsigargin both increased Ca2+(i) concentrations (pEC50s of 7.59+/-0.57 and
      6.81+/-0.31 respectively), but were unable to prime for MDC responses, suggesting
      the priming mechanism was not dependent upon increases in Ca2+(i) concentrations.
      Priming of the MDC response was still observed when experiments were performed
      with low Ca2+(e) (70 microM), indicating that Ca2+ influx was not required for
      ATP to prime the CCR4 receptor. Neither Ro31-8220 nor wortmannin affected
      priming, suggesting that protein kinase C and phosphoinositol 3-kinase were not
      involved. In conclusion, pre-stimulation of endogenous P2Y receptors with ATP
      facilitates Ca2+ signalling at the recombinant CCR4 receptor in CHO cells,
      although the mechanism by which this occurs remains to be defined.

PMID- 15167984
TI  - Embryonic turkey liver: activities of biotransformation enzymes and activation of
      DNA-reactive carcinogens.
AB  - Avian embryos are a potential alternative model for chemical toxicity and
      carcinogenicity research. Because the toxic and carcinogenic effects of some
      chemicals depend on bioactivation, activities of biotransformation enzymes and
      formation of DNA adducts in embryonic turkey liver were examined. Biochemical
      analyses of 22-day in ovo turkey liver post-mitochondrial fractions revealed
      activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD),
      7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase
      (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT).
      Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme
      activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two
      fold or higher levels by day 22. In contrast, acute administration of 3
      methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities.
      Bioactivation of structurally diverse pro-carcinogens was also examined using
      (32)P-postlabeling for DNA adducts. In ovo exposure of turkey embryos on day 20
      of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline)
      (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline
      (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21.
      Some of the DNA adducts had (32)P-postlabeling chromatographic migration patterns
      similar to DNA adducts found in livers from Fischer F344 rats exposed to the same
      pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of
      chemical biotransformation and activation of genotoxic carcinogens to form DNA
      adducts. Thus, turkey embryos could be utilized to investigate potential chemical
      toxicity and carcinogenicity.

PMID- 15167985
TI  - Establishing the compliance in elderly women for use of a low level mechanical
      stress device in a clinical osteoporosis study.
AB  - Non-pharmacologic approaches to prevent bone loss are well suited for elderly
      patients to avoid polypharmacy and medication side effects. One potential
      treatment is a vibrating platform that delivers low-level mechanical loading
      stimulating bone remodeling. However, compliance is a major concern with any
      daily treatment, and is unknown for an elderly group using this device. Thus we
      assessed compliance with standing 10 min/day on a vibrating platform device in
      elderly women, the target population for osteoporosis therapy. We also assessed
      satisfaction with daily use of the device. We conducted a randomized, placebo
      controlled, double-blinded 6-month study for daily use of a 10-min vibrating
      platform treatment in elderly women who were residents of a Continuing Care
      Retirement community. Compliance for each subject was calculated as the number of
      days attended divided by the 182 days in the 6-month trial. The 24 elderly women
      (mean age 86, range 79-92 years) had 83% compliance (95% CI: 70.5, 94.5) for
      daily treatment over 6 months. Excluding three study drop-outs, the 21 women had
      93% compliance (95% CI: 89.8, 95.6), with no difference in compliance between
      active and placebo treatment. Main reasons for missing treatment days over the 6
      months were vacation (54% of missed days) and illness (29%). Three adverse events
      occurred; one (syncope) was possibly related to device use, whereas the other two
      were not related to device use. Among participants, 95% reported overall
      satisfaction with daily use of the vibrating platform, and 57% preferred the
      platform versus daily oral medications for prevention of bone loss. Elderly women
      showed high compliance, high satisfaction and few adverse experiences with a
      daily non-pharmacological treatment designed to inhibit bone loss. Larger
      randomized controlled trials should evaluate the long-term efficacy of vibrating
      platform devices for treatment of low bone mass and osteoporosis in elderly
      individuals.

PMID- 15167986
TI  - Bone mineral density of the spine and femur in healthy Saudis.
AB  - The reference values of bone mineral density (BMD) were determined in healthy
      Saudis of both sexes and compared with US / northern European and other reference
      data. BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar
      spine and femur including subregions: trochanter, Ward's triangle, and neck, in
      1,980 randomly selected Saudis (age range 20-79 years; 915 males and 1,065
      females) living in the Jeddah area. Age-related changes in BMD were similar to
      those described in US / northern European and Lebanese reference data. Decreases
      in BMD of males were evident (% per year): 0.3-0.8 (lumbar spine), 0.2-0.4
      (femoral trochanter), 0.2-1.4 (Ward's triangle), and 0.2-0.7 (femoral neck).
      Also, decreases in BMD of females were observed (% per year): 0.8-0.9 (lumbar
      spine), 0.7-0.9 (Ward's triangle), and 0.3-0.7 (femoral neck). Using stepwise
      multiple regressions that included both body weight and height, the former had 2
      4 times greater effect on BMD than the latter. Using the mean BMD of the <35-year
      old group the T-score values were calculated for Saudis. The prevalence of
      osteoporosis in Saudis (50-79 years) at the lumbar spine using the manufacturer's
      vs Saudi reference data was 38.3-47.7% vs 30.5-49.6 (P<0.000), respectively.
      Similarly, based on BMD of total femur, the prevalence of osteoporosis using the
      manufacturer's vs Saudi reference data was 6.3-7.8% vs 1.2-4.7% (P<0.000),
      respectively. Saudis (> or =50 years) in the lowest quartile of body weight
      exhibited higher prevalence of osteoporosis (25.6% in females and 15.5% in males)
      as compared to that of the highest quartiles (0.0% in females and 0.8% in males).
      The present study underscores the importance of using population-specific
      reference values for BMD measurements to avoid overdiagnosis and/or
      underdiagnosis of osteoporosis.

PMID- 15167987
TI  - Significance of intima-media thickness in femoral artery in the determination of
      calcaneus osteo-sono index but not of lumbar spine bone mass in healthy Japanese
      people.
AB  - The aim of this cross-sectional study was to investigate whether physical
      activity and local arterial thickening may affect bone metabolism. To analyze the
      effects of physical activity and atherosclerosis on bone in healthy Japanese
      people, health-related quality of life (HRQL) and local arterial thickening were
      assessed by means of the Medical( )Outcomes Study 36-item Short Form (SF-36), and
      intimal-medial thickness (IMT) in common carotid artery (CA) and femoral artery
      (FA), respectively. Bone mineral density (BMD) in lumbar spine was measured by
      dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the
      calcaneus by ultrasound. Healthy subjects (106 male and 154 female) were
      recruited from those who participated in a local health check program at the
      Osaka City University Hospital. A significant correlation existed between lumbar
      spine BMD and calcaneus OSI (r=0.551, P<0.0001). Among various scores in SF-36,
      only physical functioning score correlated weakly but significantly in a positive
      manner with lumbar spine BMD (rho=0.156, P=0.0147) and calcaneus OSI (rho=0.190,
      P=0.0024). Lumbar spine BMD correlated negatively with FA IMT (rho=-0.191,
      P=0.0027) whereas calcaneus OSI with FA IMT (rho=-0.199, P=0.0014). Multiple
      regression analyses revealed a significant association between FA IMT and
      calcaneus OSI, whereas lumbar spine BMD did not correlate significantly with FA
      or CA IMT. When subjects were restricted to female, FA IMT, but not CA IMT, still
      showed tendency against independent factors negatively associated with calcaneus
      OSI. Furthermore, lumbar spine BMD, but not calcaneus OSI, was weakly but
      significantly associated with increased physical functioning score independently.
      In conclusion, it was suggested that physical activity may affect bone strength
      in lumbar spine and calcaneus and that FA IMT might be a significant determinant
      of bone strength in calcaneus, but not in lumbar spine, in healthy Japanese
      subjects.

PMID- 15167989
TI  - The impact of compliance with osteoporosis therapy on fracture rates in actual
      practice.
AB  - BACKGROUND: Clinical trials have demonstrated that drug therapy can reduce
      osteoporosis-related fracture risk in women over 50 years of age. Noncompliance
      could considerably limit the effectiveness observed in actual practice, however.
      The objective of this study was therefore to estimate fracture risk in relation
      to compliance with osteoporosis medication in actual practice. METHODS:
      Demographic, prescription drug use, physician services, and hospitalization
      information for women with osteoporosis who were dispensed an osteoporosis
      medication between 1996 and 2001 was obtained from the Saskatchewan health data
      files. Compliance to treatment was defined as drug available to cover 80% of the
      time. Subsequent fractures were identified via hospitalizations or physician
      contacts with a relevant diagnostic or procedure code. The risk of fractures in
      relation to compliance was examined using a Cox proportional hazards model with
      time-dependent covariates. The impact of other patient characteristics, including
      age, having suffered a prior fracture, and prior use of osteoporosis medication
      and steroids, was also examined. RESULTS: 11,249 women suffering from
      osteoporosis were identified with a mean age at the time of the index
      prescription of 68.4 years and average follow-up of 2 years. The overall fracture
      rate was 4.5% per year. Patients who complied experienced a 16% lower fracture
      rate. This association was maintained within subgroups and after controlling for
      other patient characteristics that independently predict the fracture rate.
      CONCLUSION: These results indicate that improving compliance in actual practice
      may significantly decrease osteoporosis-related fracture risk.

PMID- 15167988
TI  - One year outcomes and costs following a vertebral fracture.
AB  - Vertebral fractures are believed to be important predictors for future vertebral
      and other fractures, leading to at least a 4- to 5-fold increase in the risk of
      subsequent fractures. However, little is known about their associated near-term
      costs. The purpose of this study was to quantify the subsequent fracture and cost
      outcomes emanating from patients with an incident vertebral fracture. A
      probabilistic decision analysis model was developed to estimate the expected cost
      of all subsequent fractures. We ran Kaplan-Meier time-to-event models on placebo
      patients in risedronate's pivotal phase III clinical trial data to determine the
      cumulative incidence or probabilities of all fractures within one year of an
      incident vertebral fracture. Unit costs for health care payers in the USA and
      Sweden for vertebral, hip, other, and forearm/wrist fractures were multiplied by
      fracture probabilities to generate the expected costs of new fractures within one
      year of incident vertebral fractures. Our analysis found that that 26.1% of
      vertebral fracture patients with a mean age of 74 years refractured within 1 year
      (vertebral 17.4%; hip 3.6%; "other" 3.5%; forearm/wrist 1.6%). The calculated
      medical costs for those patients who refracture within 1 year was $5906 and 3670
      euros for the USA and Sweden, respectively, while the weighted average cost
      across all patients (refracture and non-fracture) within a year of their incident
      fracture was $1541 (USA) and 958 euros (Sweden). These results suggest that
      therapies with proven, rapid efficacy may offer important economic value to
      healthcare payers, providers and patients.

PMID- 15167990
TI  - Eminence, or rather eloquence, or rather economy-based medicine?

PMID- 15167991
TI  - Prevalence of urinary leakage in nulliparous women with respect to physical
      activity and micturition habits.
AB  - In order to survey the influence of physical activity and micturition habits on
      urinary leakage (UL) in women before their first pregnancy, a study including 725
      women attending nine maternity clinics in the northwest area of Stockholm was
      performed. During the 36th gestational week the women answered a questionnaire
      regarding the pre-pregnancy situation regarding UL, micturition habits and
      physical activity. Thirty-nine percent of the women, mean age of 28 (range 17-43)
      years, had experienced occasional UL. Of these, the majority (79%) had symptoms
      of stress urinary leakage and 21% had urge symptoms. Two percent were incontinent
      according to the definition of the International Continence Society (ICS). In a
      multivariate analysis age, inability to interrupt the urine flow and high-impact
      physical activity turned out to be independent risk factors for UL and thus
      should be observed together with traditional factors concerning UL in nulliparous
      women.

PMID- 15167993
TI  - A study of quality of life in primigravidae with urinary incontinence.
AB  - This study aimed to establish the prevalence and effect of urinary incontinence
      on quality of life during pregnancy and after parturition. A prospective cohort
      of primigravidae was recruited. The Kings Health Questionnaire (KHQ) was self
      administered antenatally (34 weeks to term) and postnatally (3 months after
      delivery). Four hundred ninety-two primigravidae were recruited. The prevalence
      of urinary incontinence was reported as: pre-pregnancy 3.5% (17/492), antenatal
      35.6% (175/492), 3-5 days postpartum 13.7% (51/370) and 3 months postnatal 13.0%
      (47/362). Most women with urinary incontinence experienced an impact on quality
      of life antenatally (54.3%) and postnatally (71.1%), although those experiencing
      an impact usually reported it as 'a little' (75.8 and 87.5%). There was a higher
      prevalence of urinary incontinence after forceps delivery ( p<0.05) but not of
      greater impairment in quality of life ( p>0.05). Personal and general health
      deteriorated postnatally ( p<0.05). During pregnancy most women with urinary
      incontinence experience minimal impact on quality of life. Postnatally, other
      causes of morbidity may contribute to worsening of general and personal health.

PMID- 15167992
TI  - Healthcare utilization among women who undergo surgery for stress urinary
      incontinence.
AB  - This study examined patterns of care for women undergoing surgery for stress
      urinary incontinence (SUI). A retrospective analysis of administrative claims
      data was performed and we identified 12520 women with a diagnosis of SUI and a
      subset of 3735 women with a surgical procedure code for SUI. For the main types
      of surgeries, we examined length of stay, pharmaceutical use, complications, and
      healthcare utilization related to incontinence greater than 6 months after
      surgery. Approximately 30% of women with a coded SUI diagnosis underwent surgery.
      Of the initial procedures, 40% were retropubic suspensions and 25% were sling
      procedures. Almost 4% of women underwent an additional surgery, and 14.1% had
      claims related to incontinence 6 or more months after the initial procedure. We
      examined medical care and pharmaceutical use for women undergoing continence
      surgery. This information may be important to patients and physicians discussing
      treatment options.

PMID- 15167994
TI  - A survey of the complications of vaginal prolapse surgery performed by members of
      the Society Of Gynecologic Surgeons.
AB  - This study aimed to examine the frequency and nature of complications of vaginal
      prolapse surgery performed by members of SGS over a year and to determine the
      feasibility and the problems associated with prospective, multicentered
      collaborative data acquisition. A survey form, which included demographics,
      surgical indications, colpopexy type, concomitant procedures, technique,
      estimated blood loss (EBL), OR time, and intra/postoperative complications, was
      distributed to society members. The nature, extent, and solution of the
      complications were examined. There were 147 members of SGS at the time of the
      study. Many were reproductive endocrinologists and gynecologic oncologists.
      Twenty-one (14%) members participated. Three hundred forty-nine (349) completed
      forms were received: 187 sacrospinous fixations (SSF), 92 colposacropexies (CSP),
      and 70 high utero sacral suspensions (HUS). There were seven (3.7%)
      intraoperative complications for SSF, seven (7.6%) for CSP and three (4.3%) for
      HUS. There were four (2.1%) postoperative complications for SSF, six (6.5%) for
      CSP and none for HUS (NS). OR time was significantly longer for CSP vs. HUS (
      P<.003) and for SSF vs. HUS ( p=.042). The EBL was significantly higher for SSF
      compared with CSP for the colpopexy procedure ( p=.013) and for entire cases (
      p<.003). Analysis showed that all three colpopexies had significant
      intraoperative and postoperative complications of less than 8%. Intraoperative
      visceral damage was a concern for all three procedures. With SSF and CSP there
      was risk of bleeding and with HUS there was a risk of ureteral obstruction.
      Postoperative CSP complications were bowel obstruction, bleeding or hernia; for
      SSF neuropathy, and for HUS none. No life-threatening intraoperative or
      postoperative complications were reported. OR time was significantly shorter for
      HUS than SSF. The highest EBL was with SSF. Only 14% of the SGS membership
      responded, despite multiple requests for participation, demonstrating the
      difficulty of multicenter data gathering.

PMID- 15167995
TI  - Intrafascial versus extrafascial abdominal hysterectomy: effects on urinary urge
      incontinence.
AB  - Our aim was to evaluate urinary urge incontinence following intrafascial and
      extrafascial abdominal hysterectomies in a prospective randomized study. Women
      scheduled for total abdominal hysterectomy were randomized to the extrafascial
      (n=38) and the intrafascial techniques (n=42). The groups were controlled for
      demographic variables, obstetric and gynecologic history, uterine size,
      indications for hysterectomy, and preoperative hemoglobin values. Short-term
      surgical morbidity and presence of urge incontinence defined as urodynamically
      established detrusor overactivity at the end of 12 months were the main outcome
      measures. Major surgical morbidity did not differ between the two groups.
      Percentages of women with urge incontinence at the end of the follow-up period
      were also similar. However, when women with pre-existing urge incontinence were
      evaluated separately, there was a trend towards the intrafascial operation to be
      associated with more urge-incontinence-free patients at the end of the follow-up
      period ( p=0.06, borderline significant). As a result, short-term surgical
      morbidity seems to be similar across the intrafascial and extrafascial techniques
      of abdominal hysterectomy. The effects of intrafascial abdominal hysterectomy on
      women presenting with urge incontinence in the preoperative period merit further
      investigation.

PMID- 15167996
TI  - Pessary reduction and postoperative cure of retention in women with anterior
      vaginal wall prolapse.
AB  - This study aimed to determine whether preoperative pessary reduction of anterior
      vaginal wall prolapse in patients with elevated postvoid residual (PVR) volumes
      relieves urinary retention, and if reconstructive pelvic surgery in these
      patients cures urinary retention. The records of all women with symptomatic
      anterior vaginal wall and urinary retention (PVR >or=100 cc) who underwent
      evaluation and surgical repair of the anterior vaginal wall at our institution
      between 1996 and 1999 were retrospectively reviewed. All patients underwent a
      detailed urogynecologic and urodynamic evaluation and had a pessary trial prior
      to surgery. Cure of urinary retention was defined as PVR <100 cc at 3 months
      postoperatively. Sensitivity, specificity, positive and negative predictive
      values for pessary reduction testing were calculated. Twenty-four patients met
      the inclusion criteria. Two patients (8%) had stage 2, eleven (46%) stage 3, and
      eleven (46%) stage 4 anterior vaginal wall prolapse. Preoperatively, the use of
      pessary was associated with relief of urinary retention in 75% patients. In
      predicting postoperative cure of urinary retention, pessary testing had a
      sensitivity of 89%, specificity of 80%, positive predictive value of 94%, and
      negative predictive value of 67%. Nineteen of 24 patients had a PVR <100 cc
      postoperatively, indicating a 79% cure rate for urinary retention. In women with
      symptomatic anterior vaginal wall prolapse and urinary retention, use of a
      pessary is associated with relief of retention in the majority of patients.
      Furthermore, pessary reduction testing has good sensitivity, specificity, and
      positive predictive value for postoperative voiding function.

PMID- 15167997
TI  - Erosion, defective healing and extrusion after tension-free urethropexy for the
      treatment of stress urinary incontinence.
AB  - A case-control study was performed in two departments performing tension-free
      urethropexy for the treatment of stress urinary incontinence. During a period of
      4.5 years, 127 cases of tension-free vaginal tape operations (TVT) and 42 cases
      of intravaginal slingplasty (IVS) were performed. In the TVT group one case of
      urethral erosion was observed, but in the IVS group six cases of defective
      healing, erosion or extrusion were observed. It is considered that the
      complications might be due to the multifilamentous nature of the IVS tape in
      contrast to the monofilamentous nature of the TVT tape.

PMID- 15167998
TI  - Tension-free vaginal tape, Burch, and slings: are there predictors for early
      postoperative voiding dysfunction?
AB  - This study compared the incidence, duration, and predictors of early
      postoperative voiding dysfunction (VD) after three continence operations. Charts
      of women undergoing tension-free vaginal tape (TVT), Burch, or suburethral sling
      were reviewed. Early postoperative VD was defined as urinary retention or
      postvoid residual (PVR) >200 ml at discharge. Analysis of variance, Chi-square,
      and non-parametric tests were used. Sixty-three TVT, 42 Burch and 33 slings were
      identified. Incidence of VD with TVT, sling, and Burch was 50, 24, and 15%,
      respectively ( P<0.001), and the mean number of days of postoperative catheter
      use was 9, 21, and 5 days, respectively ( P=0.04). Patients with VD, compared
      with those with normal voiding, had smaller preoperative PVR (50 vs. 75 ml,
      P=0.005), longer catheterization (29 vs. 3 days, P<0.001), and more urinary tract
      infections (43 vs. 15%, P<0.001). Early postoperative VD is an underreported but
      frequent postoperative complication which is difficult to predict.

PMID- 15167999
TI  - Are there any factors predicting the cure and complication rates of tension-free
      vaginal tape?
AB  - Predictive factors that could possibly affect the cure and complication rates of
      tension-free vaginal tape (TVT) in the treatment of stress urinary incontinence
      (SUI) were investigated. Seventy-five consecutive patients with urodynamically
      proven SUI and who had undergone a TVT operation were evaluated according to a
      follow-up protocol. Median age was 51.2 (33-69). Thirteen (17%) of the patients
      had had previous anti-incontinence surgery. Sixteen (21%) patients had complained
      of pure stress and 59 (79%) of mixed incontinence. Valsalva leak point pressure
      (VLPP) values had been found to be below 60 cmH(2)O in 36 (48%) and over 60
      cmH(2)O in 39 (52%) patients, while detrusor overactivity (DO) had been detected
      in six (8%) patients during urodynamic evaluation. Local, general, and epidural
      anesthesia had been performed in 43 (57%), 29 (39%), and three (4%) patients,
      respectively. Univariate analyses were done using Fisher's exact and Chi-square
      tests. Multivariate analyses were done using logistic regression test to
      determine predictive factors affecting cure and complication rates. Mean surgical
      and hospitalization times were 34.7 min (20-70) and 1.2 days (1-5), respectively.
      Mean follow-up was 21.6 months (6-38). Cure and improvement rates were 89 and 8%,
      respectively. Thirty-one complications were observed in 27 (36%) patients.
      Intraoperative bladder perforation and bleeding occurred in three (4%) and two
      (3%) patients, respectively. Sixty-six (88%) patients voided spontaneously after
      TVT while nine (12%) performed clean intermittent catheterization (CIC) for a
      period of time. Seven of nine patients regained the spontaneous voiding ability
      within 1 month. The tape was cut in two of these retentive patients and one with
      severe storage lower urinary tract symptoms (LUTS) either unilaterally or
      bilaterally. On univariate (Fisher's exact test, p =0.018), and multivariate
      (Logistic regression, p =0.013) analyses, patient age was the only statistically
      significant parameter affecting the cure rate, which was significantly lower
      particularly over 55 years of age. No significant factor predicting the
      complications was detected. TVT is an effective and safe surgical procedure in
      the treatment of SUI. In this study age was the only significant predictive
      factor affecting the cure rate while no significant factor predicting the
      complications was detected. Cure rate was significantly lower in patients over 55
      years of age.

PMID- 15168000
TI  - Correlation between valsalva leak point pressure and maximal urethral closure
      pressure in women with stress urinary incontinence.
AB  - This study analyzed the relationship between valsalva leak point pressure (VLPP)
      and maximal urethral closure pressure (MUCP) in women with stress urinary
      incontinence. One hundred sixty-one patients were selected with diagnosis of
      mixed or stress urinary incontinence. During urodynamics we measured VLPP and
      MUCP. Patients were gathered according to VLPP and analysis of variance (ANOVA)
      was performed. Pearson's correlation coefficient and linear regression were also
      utilized. The group with VLPP under 60 cm H(2)O had mean MUCP of 44.5 cm H(2)0;
      the group with VLPP between 60 and 90 cm H(2)O had mean MUCP of 54.3 cm H(2)O;
      and the group with VLPP over 90 cm H(2)O had mean MUCP of 60.1 cm H(2)O. We
      observed correlation between MUCP and VLPP when we used Pearson's correlation
      coefficient (r=0.22) and linear regression ( p<0.05). There was weak correlation
      between MUCP and VLPP, and MUCP was significantly lower in patients with leak
      point pressure inferior to 60 cm H(2)O.

PMID- 15168002
TI  - Is an indwelling catheter necessary for bladder drainage after modified Burch
      colposuspension?
AB  - Catheterization is considered to be a mandatory procedure for adequate bladder
      drainage following an anti-incontinence operation until the recovery of normal
      voiding function occurs. We conducted this prospective study to challenge this
      practice. A total of 86 patients with genuine stress incontinence who underwent a
      modified Burch coplosuspension were randomized into two groups based on the day
      of operation. The study group consisted of 42 patients who had the transurethral
      Foley catheter removed postoperatively the next morning (Group A). The control
      group was composed of 43 patients who had the transurethral indwelling catheter
      left in place until the fifth postoperative day (Group B). The percentages of
      immediate voiding difficulties in Groups A and B were 7.1% and 0%, respectively (
      P>0.05). The postoperative urinary tract infection rates of Groups A and B were
      16.6% and 23.3%, respectively ( P>0.05). The success rates of our patients were
      not compromised after our modified operative procedures (78.6% with dry results
      and 19.0% with improved symptoms in Group A vs. 74.4% with dry results and 20.9%
      with improved symptoms in Group B, P >0.05). Our results imply that it is not
      necessary that an indwelling catheter, for bladder drainage, be left in place
      until the fifth postoperative day to prevent immediate voiding difficulties.

PMID- 15168001
TI  - Different clinical presentation of interstitial cystitis syndrome.
AB  - The aim of the study was to examine how interstitial cystitis (IC) initiates its
      clinical course, which changes as the disease progresses from the initial phase
      to its full clinical manifestation. Patients diagnosed with IC between 1998 and
      2003 in our department were evaluated and reviewed regularly. The exact onset of
      urinary symptoms was recorded. Diagnosis of IC was made by National Institute of
      Diabetes and Digestive and Kidney Disease (NIDDK) criteria when clinical
      suspicion of IC was present. The study group included 30 female patients who were
      27-69 years old when diagnosis was made. Mean age was 46.7. Seventy percent of
      patients had only one symptom at onset. The most frequent initial diagnosis was
      urinary tract infection (UTI). A condition of recurrent bacterial UTIs, with
      subsequent persistence of symptoms and negative cultures, could be detected as a
      harbinger of IC in 60% of our patient group. IC may manifest initially with a
      single symptom in its early stage, when diagnosis is perhaps less easy, but
      adequate and effective treatment can still be offered to the patient.

PMID- 15168003
TI  - Urethral resistance measurement: a new method for evaluation of stress urinary
      incontinence in women.
AB  - The aim of this study was to evaluate a new method to measure urethral resistance
      among 66 women with urinary incontinence. A stainless steel sphere attached to a
      guide wire was developed. The sphere is inserted into the bladder and withdrawn
      through the urethra at a steady rate. Serial measurements with spheres of 5, 6
      and 7 mm were performed. The mean urethral resistance as measured by the largest
      sphere (0.07+/-0.03) was significantly greater than that measured by the medium
      sphere (0.06+/-0.02, p<0.0001), which was significantly larger than that measured
      by the smallest sphere (0.04+/-0.01, p<0.0001). There was good correlation of
      urethral resistance with maximum urethral closure pressure (MUCP) by this
      technique, but no correlation with Valsalva leak point pressure (VLPP).

PMID- 15168004
TI  - An adult female epispadias without exstrophy was presented with urinary
      incontinence: a case report.
AB  - A 39-year-old woman with three children presented with primary severe urinary
      incontinence. Epispadias without exstrophy was determined in physical
      examination. The single-stage procedure including vulvoplasty and modified Young
      Dees-Leadbetter bladder neck repair was performed to obtain sufficient cosmetic
      outcome and continence. Excellent functional and cosmetic results were obtained.

PMID- 15168005
TI  - Pelvic organ prolapse after uterine artery embolization for uterine myoma.
AB  - Uterine artery embolization (UAE) is gaining popularity as a treatment modality
      in patients with symptomatic uterine fibroids who do not desire fertility.
      Complications of this procedure can be serious and disabling. A 50-year-old woman
      presented with stage II uterovaginal prolapse after UAE for symptomatic uterine
      fibroids. Pelvic organ prolapse developed 16 months after the initial procedure.
      Surgical correction was performed. This is the first case report of pelvic organ
      prolapse after UAE. Normal prior gynecological examinations, and absence of
      pelvic pressure symptoms, indicate that pelvic organ prolapse had occurred
      subsequent to UAE.

PMID- 15168006
TI  - Posterior cervical lip for juxtacervical vesicovaginal fistula closure (M.
      Ijaiya's technique).
AB  - The use of the posterior lip of the cervix to close juxtacervical fistulae (M.
      Ijaiya's technique) may be particularly useful when the anterior lip of the
      cervix is involved in the pressure necrosis and it is difficult to achieve a
      tension-free repair. This technique is recommended for postmenopausal patients
      with a normal cervical smear and endometrial biopsy. It is easier, less time
      consuming and less bloody than abdominal route repair. Vaginal capacity is
      preserved.

PMID- 15168007
TI  - The Oxford unicompartmental knee prosthesis: a 2-14 year follow-up.
AB  - Our medium- and long-term results obtained with the Oxford unicompartmental knee
      prosthesis for unicompartmental knee osteoarthrosis are presented. Ninety-seven
      prostheses were evaluated (87 medial, 10 lateral) in 86 patients, with the
      Hospital for Special Surgery knee score after 2-14 years (mean follow-up: 6 years
      9 months). Five prostheses were lost to follow-up. Eight patients died, not
      related to surgery; none had undergone a revision. Fourteen revisions (of which
      one bilateral UKP), 11 medial and three lateral, were performed. The mean HSS
      score of the 69 UKPs was 178.8 (80% excellent, 10% good, 4% fair, 6% poor). These
      findings confirm the good results reported in other studies, regarding proper
      patient selection and a consistent operative technique.

PMID- 15168008
TI  - Knee arthroscopy with different anesthesia methods: a comparison of efficacy and
      cost.
AB  - To evaluate the cost and time effectiveness for different anesthesia methods when
      performing knee arthroscopy, this study compared three different anesthesia
      methods. Four hundred healthy patients scheduled for knee arthroscopy were
      randomized to either local anesthesia (LA) (n=200), spinal anesthesia (SA)
      (n=100) or general anesthesia (GA) (n=100). The LA arthroscopies were performed
      in a facility set up in our outpatient department without anesthesia service. The
      SA and GA arthroscopies were performed in our central operating department with
      full anesthesia service. Comparisons were made between total hospital stay,
      anesthesia time, surgery time, recovery time, pharmaceutical and total cost. The
      total hospital time was 130.4 min (SD 35.14, range 63-383) in the LA group
      compared to 280.4 min (SD 79.29, range 155-589) in the GA group (p<0.001). The
      total hospital time in the GA group was also shorter than that of 350.3 min (SD
      65.37, range 198-502) in the SA group (p<0.001). The time from start of
      anesthesia to start of surgery was significantly longer in the LA group, 39.2 min
      (SD 13.13, range 17-87), compared to 20.1 min (SD 4.93, range 11-35) in the SA
      group and to 17.6 min (SD 4.64, range 9-44) in the GA group. There were no
      differences in the surgery time for the three groups. The use of LA was shown to
      save SEK 1011 (Swedish Crowns) per patient compared to SA and GA.

PMID- 15168009
TI  - Severe myocardial depression following intravenous nimodipine for aneurysmal
      subarachnoid haemorrhage.

PMID- 15168010
TI  - Calpain I inhibitor ameliorates the indices of disease severity in a murine model
      of cerulein-induced acute pancreatitis.
AB  - OBJECTIVE: Nuclear factor-kappaB (NF-kappaB) is a transcription factor which
      plays a pivotal role in the induction of genes involved in the response to injury
      and inflammation. Calpain I inhibitor is a potent antioxidant which is an
      effective inhibitor of NF-kappaB. This study examined whether the postulate that
      calpain I inhibitor attenuates experimental acute pancreatitis. DESIGN AND
      SETTING: In a murine model we measured NF-kappaB activation, expression of
      intercellular adhesion molecule (ICAM) 1, nitrotyrosine, inducible nitric oxide
      synthase (iNOS), nuclear enzyme poly(ADP-ribose) synthetase (PARS),
      myeloperoxidase, malondialdehyde, amylase and lipase and determined histological
      evidence of lung and pancreas injury in four groups: control (saline only),
      cerulein, calpain I inhibitor plus cerulein and calpain I inhibitor plus saline.
      MEASUREMENTS AND RESULTS: Intraperitoneal injection of cerulein in mice resulted
      in severe, acute pancreatitis characterised by oedema, neutrophil infiltration,
      tissue haemorrhage and necrosis and elevated serum levels of amylase and lipase.
      Infiltration of pancreatic and lung tissue with neutrophils (measured as increase
      in myeloperoxidase activity) was associated with enhanced lipid peroxidation
      (increased tissue levels of malondialdehyde). Immunohistochemical examination
      demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS and
      PARS in the pancreas and lung of cerulein-treated mice. In contrast, pre
      treatment with calpain I inhibitor markedly reduced: the degree of pancreas and
      lung injury; upregulation/expression of ICAM-1; staining for iNOS, nitrotyrosine
      and PARS; and lipid peroxidation. Additionally, calpain I inhibitor treatment
      significantly prevented the activation of NF-kappaB as suggested by the
      inhibition of IkappaB-alpha; degradation in the pancreas tissues after cerulein
      administration. CONCLUSIONS: Taken together, our results clearly demonstrate that
      prevention of the activation of NF-kappaB by calpain I inhibitor ameliorates
      experimental murine acute pancreatitis.

PMID- 15168013
TI  - The assumed problem of air bubbles in the tubing during intra-abdominal pressure
      measurement.

PMID- 15168012
TI  - Hypothermia inhibits cytokine release of alveolar macrophage and activation of
      nuclear factor kappaB in endotoxemic lung.
AB  - OBJECTIVE: We have previously reported that endotoxin-induced neutrophil
      infiltration of the lung is lower during hypothermia than during normothermia.
      Because neutrophil infiltration of the lung is considered a downstream phenomenon
      following an activation of tissue macrophages, we examined the effects of induced
      hypothermia on the proximal aspects of acute lung injury, which involves alveolar
      macrophages and nuclear transcription of cytokine genes. DESIGN AND SETTING:
      Animal study in an institutional animal laboratory. SUBJECTS: Thirty-six Sprague
      Dawley rats. INTERVENTIONS: Rats were assigned to the following groups:
      normothermia (37 degrees C) with saline; hypothermia (27 degrees C) with saline;
      normothermia with lipopolysaccharide; hypothermia with lipopolysaccharide. After
      1 h of stable temperature rats were intraperitoneally given lipopolysaccharide or
      an equivalent volume of normal saline. The temperature of rats was maintained
      within +/-1 degrees C of the target temperature for the subsequent 2 h, after
      which rats were subjected to lung lavage. MEASUREMENTS AND RESULTS: Neutrophil
      count, TNF-alpha, and IL-1beta in lavage fluid were all higher with normothermia
      LPS than in normothermia-saline. Neutrophil count, TNF-alpha, and IL-1beta levels
      of lavage fluid were lower with hypothermia-LPS than with normothermia-LPS. TNF
      alpha release from cultured alveolar macrophages and NF-kappaB activity in lung
      tissue were both lower with hypothermia-LPS than with normothermia-LPS. I
      kappaBalpha level in lung tissue was lower with normothermia-LPS than with the
      normothermia-saline, whereas I-kappaBalpha level in lung tissue did not differ
      between normothermia-saline and hypothermia-LPS. CONCLUSIONS: Induced hypothermia
      suppressed the release of inflammatory cytokine from alveolar macrophages and NF
      kappaB activation in endotoxemic lung.

PMID- 15168014
TI  - Identification of a new case of hepatocyte nuclear factor-1beta mutation with
      highly varied phenotypes.

PMID- 15168015
TI  - Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with
      Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and
      not insulin responsiveness.
AB  - AIMS/HYPOTHESIS: Our aim was to examine the possible direct relationship of
      interleukin-6 and TNFalpha with insulin sensitivity in humans. METHODS: We
      carried out two series of euglycaemic-hyperinsulinaemic clamp experiments. In the
      first (CLAMP1), skeletal muscle mRNA expression and plasma concentrations of IL-6
      and TNFalpha were examined in patients with Type 2 diabetes ( n=6), subjects
      matched for age (n=6), and young healthy (n=11) control subjects during a 120-min
      supra-physiological hyperinsulinaemic (40 mU.m(-2).min(-1)) euglycaemic clamp. In
      the second series of experiments (CLAMP2), patients with Type 2 diabetes (n=6)
      and subjects matched for age (n=7) were studied during a 240-min high
      physiological hyperinsulinaemic (7 mU.m(-2).min(-1)) euglycaemic clamp, during
      which arterial and venous (femoral and subclavian) blood samples were measured
      for IL-6 and TNFalpha flux. RESULTS: In both experiments the glucose infusion
      rate in the patients was markedly lower than that in the other groups. In CLAMP1,
      basal skeletal muscle IL-6 and TNFalpha mRNA were the same in all groups. They
      were not affected by insulin and they were not related to the glucose infusion
      rate. In CLAMP2, neither cytokine was released from the arm or leg during insulin
      stimulation in either group. In both experiments plasma concentrations of these
      cytokines were similar in the patients and in the control subjects, although in
      CLAMP1 the young healthy control group had lower (p<0.05) plasma IL-6
      concentrations. Using data from all subjects, a strong positive correlation
      (r=0.85; p<0.00001) was observed between basal plasma IL-6 and BMI. Conversely, a
      negative relationship (r=-0.345; p<0.05) was found between basal plasma TNFalpha
      and BMI, although this was not significant when corrected for BMI. When corrected
      for BMI, no relationship was observed between either basal plasma IL-6 or
      TNFalpha and GIR. CONCLUSIONS/INTERPRETATION: These data show that the increased
      circulating IL-6 concentrations seen in patients with Type 2 diabetes are
      strongly related to fat mass and not insulin responsiveness, and suggest that
      neither IL-6 nor TNFalpha are indicative of insulin resistance.

PMID- 15168016
TI  - Nelfinavir-induced insulin resistance is associated with impaired plasma membrane
      recruitment of the PI 3-kinase effectors Akt/PKB and PKC-zeta.
AB  - AIMS/HYPOTHESIS: Chronic exposure of 3T3-L1 adipocytes to the HIV protease
      inhibitor nelfinavir induces insulin resistance, recapitulating key metabolic
      alterations of adipose tissue in the lipodystrophy syndrome induced by these
      agents. Our goal was to identify the defect in the insulin signal transduction
      cascade leading to nelfinavir-induced insulin resistance. METHODS: Fully
      differentiated 3T3-L1 adipocytes were exposed to 30 micro mol/l nelfinavir for 18
      h, after which the amount, the phosphorylation and the localisation of key
      proteins in the insulin signalling cascade were evaluated. RESULTS: Insulin
      induced interaction of phosphatidylinositol 3'-kinase (PI 3-kinase) with IRS
      proteins was normal in cells treated with nelfinavir, as was IRS-1-associated PI
      3-kinase activity. Yet insulin-induced phosphorylation of Akt/protein kinase B
      (PKB), p70S6 kinase and extracellular signal-regulated kinase 1/2 was
      significantly impaired. This could not be attributed to increased protein
      phosphatase 2A activity or to increased expression of phosphoinositide
      phosphatases (SHIP2 or PTEN). However, insulin failed to induce translocation of
      the PI 3-kinase effectors Akt/PKB and protein kinase C-zeta (PKC-zeta) to plasma
      membrane fractions of nelfinavir-treated adipocytes. CONCLUSIONS/INTERPRETATION:
      We therefore conclude that nelfinavir induces a defect in the insulin signalling
      cascade downstream of the activation of PI 3-kinase. This defect manifests itself
      by impaired insulin-mediated recruitment of Akt/PKB and PKC-zeta to the plasma
      membrane.

PMID- 15168017
TI  - Physiological hyperinsulinaemia increases intramuscular microvascular reactive
      hyperaemia and vasomotion in healthy volunteers.
AB  - AIMS/HYPOTHESIS: Insulin possesses vasodilatory actions that may be important in
      regulating its access to insulin-sensitive tissues. Our study aims to directly
      measure changes in response to insulin in the human skeletal muscle
      microcirculation. Measurement was by an implanted laser Doppler probe. METHODS:
      We investigated changes in intramuscular and skin microvascular perfusion in 12
      healthy individuals during a hyperinsulinaemic and a control clamp. We determined
      leg blood flow with plethysmography, finger skin functional capillary recruitment
      with capillaroscopy, endothelium-(in)dependent vasodilation by iontophoresis of
      acetylcholine and sodium nitroprusside, and leg intramuscular reactive hyperaemia
      and vasomotion with laser Doppler measurements. RESULTS: Compared to the control
      study, hyperinsulinaemia (416+/-82 pmol/l) caused: (i) an increase in leg blood
      flow (1.0+/-1.0 vs 0.1+/-0.6 ml.min(-1).100 ml, p<0.05); (ii) an increase in
      finger skin capillary recruitment (14.9+/-10.1 vs -5.6+/-11.0%, p<0.01); (iii) no
      change in baseline laser Doppler perfusion either in finger skin or leg muscle;
      (iv) a tendency to increase acetylcholine-mediated vasodilation (475+/-534 vs
      114+/-337%, p=0.07) with no change in sodium-nitroprusside-mediated vasodilation
      ( p=0.2) in finger skin; (v) an increase in intramuscular reactive hyperaemia
      (423+/-507 vs 0+/-220%, p<0.01); and (vi) a decrease in time needed to reach peak
      intramuscular perfusion (-3.6+/-3.0 vs 1.1+/-3.1 s, p<0.01). In addition,
      hyperinsulinaemia induced an increase in intramuscular vasomotion by increasing
      the contribution of frequencies between 0.01 and 0.04 Hz ( p<0.05 for all), which
      probably represents increased endothelial and neurogenic activity.
      CONCLUSIONS/INTERPRETATION: Physiological hyperinsulinaemia not only stimulates
      total blood flow and skin microvascular perfusion, but also augments human
      skeletal muscle microvascular recruitment and vasomotion as detected directly by
      laser Doppler measurements.

PMID- 15168019
TI  - BABYDIET, a feasibility study to prevent the appearance of islet autoantibodies
      in relatives of patients with Type 1 diabetes by delaying exposure to gluten.

PMID- 15168020
TI  - Supplementation with trans10cis12-conjugated linoleic acid induces
      hyperproinsulinaemia in obese men: close association with impaired insulin
      sensitivity.
AB  - AIMS/HYPOTHESIS: Hyperproinsulinaemia reflects both beta cell dysfunction and
      insulin resistance in cross-sectional studies, but it is not known whether
      changes in proinsulin concentrations are related to insulin resistance over time.
      As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces
      insulin resistance in obese men, we used this fatty acid to investigate the
      effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations,
      including their associations with change in insulin sensitivity. METHODS: We
      randomised (double-blind) 57 non-diabetic abdominally obese men to receive either
      3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin
      sensitivity (hyperinsulinaemic-euglycaemic clamp), intact proinsulin, insulin,
      the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed
      before and after supplementation. RESULTS: Supplementation with t10c12CLA
      increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C
      peptide concentrations (p<0.001) in comparison with control subjects.
      Adiponectin, however, did not change significantly. The change in proinsulin, but
      not the proinsulin : insulin ratio, was related to impaired insulin sensitivity
      (r= -0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose,
      adiponectin and BMI. Conversely, the correlation between insulin sensitivity and
      specific insulin (r=-0.46, p<0.001) did not remain significant after adjustment
      for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin
      concentrations ( r= -0.34, p<0.01). CONCLUSIONS/INTERPRETATION: In obese men,
      t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin
      sensitivity, independently of changes in insulin concentrations. These results
      are of clinical interest, as hyperproinsulinaemia predicts diabetes and
      cardiovascular disease. The use of weight-loss supplements containing this fatty
      acid is worrying.

PMID- 15168018
TI  - Expression of fatty-acid-handling proteins in human adipose tissue in relation to
      obesity and insulin resistance.
AB  - AIMS/HYPOTHESIS: Protein-mediated trans-membrane and intracellular fatty acid
      trafficking are becoming increasingly recognised as biochemically and
      physiologically important concepts. Obesity and insulin resistance are polygenic
      disorders, heavily influenced by environmental and life-style factors, and are
      virtually always associated with disturbed fatty acid metabolism in adipose and
      other tissues. The aim of this study was to investigate mRNA expression levels of
      fatty-acid-handling proteins in adipose tissue in relation to markers of genetic
      and acquired obesity and insulin resistance. METHODS: We quantified mRNA
      expression of subcutaneous adipose tissue fatty-acid-handling proteins (ALBP,
      KLBP, FATP1, FATP4, CD36, ACS1) in 17 monozygotic twin-pairs with a range of
      intra-pair differences (Delta) in BMI and detailed measures of obesity and
      insulin resistance, allowing influences of genetic and non-genetic factors to be
      distinguished. RESULTS: In acquired obesity FATP4 expression was up-regulated
      independently of genetic background (DeltaFATP4 versus DeltaBMI; r=0.50, p=0.04;
      DeltaFATP4 versus Deltabody fat; r=0.59, p=0.01). Similarly, CD36 and FATP1
      expression correlated with acquired differences in HDL cholesterol and non
      esterified fatty acid concentrations respectively. Moreover, FATP4 and CD36
      expression levels correlated with measures of obesity and insulin resistance that
      are influenced by both genetic and non-genetic factors (FATP4 versus BMI: r=0.53,
      p=0.0001; FATP4 versus body fat: r=0.51, p=0.002; FATP4 versus homeostasis model
      assessment [HOMA]: r=0.49, p=0.001; CD36 versus BMI: r=0.50, p=0.02; CD36 versus
      body fat: r=0.63, p=0.001; CD36 versus HOMA: r=0.34, p=0.06).
      CONCLUSIONS/INTERPRETATION: These findings indicate that expression of specific
      adipose tissue fatty-acid-handling proteins is related to obesity and insulin
      resistance, and that, in particular, FATP4 plays a role in acquired obesity. Our
      results suggest that facilitated fatty acid trafficking is a physiologically and
      pathologically relevant phenomenon in man.

PMID- 15168021
TI  - The time has come to target connective tissue growth factor in diabetic
      complications.

PMID- 15168024
TI  - QTL analysis of quality traits in an advanced backcross between Prunus persica
      cultivars and the wild relative species P. davidiana.
AB  - Genetic control of the different attributes involved in peach quality has been
      investigated in an advanced backcross population derived from a cross between
      Prunus davidiana clone P1908, a wild parent with poor agronomic performance, and
      a commercial variety, Summergrand. A total of 24 physical and biochemical traits
      were investigated. Quantitative trait loci (QTLs) were detected for all the
      traits studied. We identified alleles from P. davidiana with agronomically
      favorable effects regarding fruit and stone sizes, sugar and acid concentrations
      and red flesh coloration, in clear contrast to its phenotype. We identified three
      main regions of the genome where alleles from P. davidiana had negative effects
      on multiple traits. In other regions, co-locations of QTLs with opposite effects
      on quality traits were also detected. We discuss the nature of these co-locations
      in the light of the probable physiological mechanisms involved. Strategies to
      cope with negative correlations between favorable traits and co-locations of P.
      davidiana alleles with negative effects on quality traits and positive effects
      regarding resistance to powdery mildew are discussed from a breeding point of
      view.

PMID- 15168022
TI  - Large-scale heterospecific segregation distortion in Populus revealed by a dense
      genetic map.
AB  - We report the most complete genetic map to have been constructed for the genus
      Populus. This map includes 544 markers mapped onto 19 linkage groups, equivalent
      to the Populus chromosome number, with all markers displaying internally
      consistent linkage patterns. We estimate the genome length to be between 2,300
      and 2,500 cM, based both on the observed number of crossovers in the maternal
      haplotypes, as well as the total observed map length. Genome coverage was
      estimated to be greater than 99.9% at 20 cM per marker. We did not detect obvious
      recombination repression in the maternal tree (a hybrid of Populus trichocarpa
      Hooker x P. deltoides Marsh.) compared to the paternal tree (pure P. deltoides).
      Finally, most markers exhibiting segregation distortion were derived from the
      donor parent in this backcross, and generally occurred in large contiguous blocks
      on two linkage groups. We hypothesize that divergent selection has occurred on
      chromosomal scales among the parental species used to create this pedigree, and
      explore the evolutionary implications of this observation. This genetic linkage
      map provides the most comprehensive view of the Populus genome reported to date
      and will prove invaluable for future inquiries into the structural and functional
      genomics, evolutionary biology, and genetic improvement of this ecologically
      important model species.

PMID- 15168023
TI  - Cold hardiness of wheat near-isogenic lines differing in vernalization alleles.
AB  - Four major genes in wheat (Triticum aestivum L.), with the dominant alleles
      designated Vrn-A1, Vrn-B1, Vrn-D1, and Vrn4, are known to have large effects on
      the vernalization response, but the effects on cold hardiness are ambiguous. Near
      isogenic experimental lines (NILs) in a Triple Dirk (TD) genetic background with
      different vernalization alleles were evaluated for cold hardiness. Although TD is
      homozygous dominant for Vrn-A1 (formerly Vrn1) and Vrn-B1 (formerly Vrn2), four
      of the lines are each homozygous dominant for a different vernalization gene, and
      one line is homozygous recessive for all four vernalization genes. Following
      establishment, the plants were initially acclimated for 6 weeks in a growth
      chamber and then stressed in a low temperature freezer from which they were
      removed over a range of temperatures as the chamber temperature was lowered 1.3
      degrees C h(-1). Temperatures resulting in no regrowth from 50% of the plants
      (LT(50)) were determined by estimating the inflection point of the sigmoidal
      response curve by nonlinear regression. The LT(50) values were -6.7 degrees C for
      cv. TD, -6.6 degrees C for the Vrn-A1 and Vrn4 lines, -8.1 degrees C for the Vrn
      D1 (formerly Vrn3) line, -9.4 degrees C for the Vrn-B1 line, and -11.7 degrees C
      for the homozygous recessive winter line. The LT(50) of the true winter line was
      significantly lower than those of all the other lines. Significant differences
      were also observed between some, but not all, of the lines possessing dominant
      vernalization alleles. The presence of dominant vernalization alleles at one of
      the four loci studied significantly reduced cold hardiness following acclimation.

PMID- 15168025
TI  - [Modern diagnosis of lung nodules].
AB  - Despite numerous technical improvements, modern diagnosis of lung nodules can
      still be divided into three partially overlapping stages: (1) detection, (2)
      characterization, and (3) follow-up and management. With respect to these steps,
      this article reviews the diagnostic significance of different modalities. New and
      not definitively evaluated techniques are considered. Furthermore, methods that
      are not routinely applied but have been published and are thought to have some
      value in the characterization of pulmonary lung nodules are discussed.
      Statistical data are included to assist the classification of the results of
      imaging. Remarks on biopsy of lung nodules to obtain histopathologic correlation
      complete this overview. The authors are convinced that the established methods
      (radiography for detection, spiral CT for characterization), after thorough
      evaluation, will soon be replaced by magnetic resonance imaging (MRI). Recent
      experience with MRI points to its potential for detection and characterization of
      pulmonary nodules while avoiding ionizing radiation. The development of
      indications for MRI of the lung (e.g. paediatric radiology) will be fascinating
      to observe.

PMID- 15168027
TI  - [Pre-auricular tumors in an infant. Differential diagnosis of neuroectodermal
      syndromes].
AB  - BACKGROUND: Neuroectodermal syndromes are complex because of their rarity and
      overlapping clinical manifestations making differential diagnosis problematic.
      CASE REPORT: A 2-year old girl presented with a phenotype characterized by
      bilateral pre-auricular tags, a fistula of the right cheek, hemifacial
      microsomia, and a limbus dermoid on the right eye. This constellation is
      characteristic for the Goldenhar syndrome. Following excision of the tags and
      fistula along with a keratoplasty, the child developed normally. CONCLUSION: The
      exact diagnosis of a neuroectodermal syndrome facilitates identification of
      associated symptoms. Early surgical therapy may prevent the development of
      functional deficits.

PMID- 15168028
TI  - [Ambulatory procedures to replace inpatient care. Background and applications].
AB  - Since January 2004, German hospitals and specialists in private practice have
      equal rights to provide and to charge for ambulatory surgeries according to
      paragraph 115b, 5th Code of Social Law. The current agreement between the German
      self-governing bodies replaces the existing contracts from 1993. In contrast to
      the previous version, the revised catalogue contains additional non-operative
      procedures. Some procedures may be provided either in an ambulatory or inpatient
      setting. However, for the hospitals it is of particular importance that some
      specified procedures should be performed on an ambulatory basis. If these
      particular services are delivered in an inpatient setting at least one stipulated
      criteria of exception has to be fulfilled. From the perspective of dermatology,
      not only opportunities but also obligations for ambulatory care arise from the
      new conditions. The critical facts and aspects with special relevance to
      dermatology are reviewed in detail.

PMID- 15168026
TI  - Targeting multiple signal transduction pathways through inhibition of Hsp90.
AB  - The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation
      and stability of a variety of proteins, many of which are crucial in oncogenesis,
      including epidermal growth factor receptor (EGF-R), Her-2, AKT, Raf, p53, and
      cdk4. These proteins are referred to as "clients" of Hsp90. Under unstressed
      conditions these proteins form complexes with Hsp90 and the cochaperones to
      attain their active conformations or enhance stability. Inhibition of Hsp90
      function disrupts the complex and leads to degradation of client proteins in a
      proteasome-dependent manner. This results in simultaneous interruption of many
      signal transduction pathways pivotal to tumor progression and survival. Based on
      the unique role of the Hsp90 complex, extensive effort has been made in
      identifying Hsp90 inhibitors. Several compounds have been shown to inhibit Hsp90
      in vitro and in vivo and the most advanced, 17-allylamino-17
      demethoxygeldanamycin (AAG), is in phase I/II clinical trials. Recent findings
      with 17-AAG indicate that tumor cells utilize Hsp90 quite differently from normal
      cells, explaining the selectivity of the drug and suggesting a central role of
      Hsp90 in malignant progression. Thus these small molecule inhibitors have proved
      not only to be of great value in identifying new Hsp90 client proteins and in
      understanding the biology of Hsp90 but are also promising therapeutics in a
      variety of tumors.

PMID- 15168029
TI  - [Design and use of patient pathways in general surgery].
AB  - BACKGROUND: Clinical pathways are a new initiative intended to reduce costs while
      maintaining or even improving the quality of care. Based on treatment guidelines,
      patient pathways display an optimal sequence of staff actions in the
      preoperative, operative, and postoperative in- and outpatient treatment. METHODS:
      In this study, patient pathways were developed for selected elective general
      surgical disease entities following a new modular approach. All elements of care
      and their direct costs to the hospital were identified. Multidisciplinary teams
      of physicians, nurses, and administrative staff constructed and implemented the
      patient pathways. RESULTS: In the 1-year pilot phase, we developed and
      implemented 7 pathways with 16 subpathways: open herniorrhaphy, laparoscopic
      cholecystectomy and fundoplication, thyroidectomy, surgical treatment of
      diverticulitis and colon carcinoma and kidney transplantation. CONCLUSIONS:
      Patient pathways combine the management of care, hospital processes, and costs in
      a new integrated concept. Patient pathways streamline and standardize care,
      facilitate communication, and contribute to cost control efforts.

PMID- 15168030
TI  - [Multiple endocrine neoplasia type 1. Surgical therapy of primary
      hyperparathyroidism].
AB  - Primary hyperparathyroidism (pHPT) occurs in about 90% of patients with multiple
      endocrine neoplasia type 1 (MEN1). In contrast to sporadic pHPT, multiple gland
      disease is most common in MEN1. The appropriate surgical approach is still
      controversial. The aim of this study was to analyze the results of surgical
      therapy of pHPT in patients with genetically confirmed MEN1. In an observational
      study, preoperative data, operative procedures, long-term results, and a possible
      genotype-phenotype correlation were analyzed in patients with pHPT and
      genetically confirmed MEN1. According to our results, tPTX+T (total
      parathyroidectomy+thymectomy+autotransplantation) seems to be a more favorable
      surgical approach in patients with MEN1 pHPT than sDE (selective gland
      exstirpation) and stPTX (subtotal parathyroidectromy) without cervical
      thymectomy, because recurrences or persistence of the disease are rare. A
      prospective randomized trial is needed to compare stPTX including cervical
      thymectomy vs tPTX+T. A genotype-phenotype correlation could not be identified.

PMID- 15168031
TI  - [Adenocarcinoma of the esophagogastric junction: prognostic factors and results
      of primary surgery].
AB  - INTRODUCTION: The incidence of adenocarcinoma of the esophagogastric junction
      (AEG) is increasing worldwide, and classification systems and resection
      procedures are being controversially discussed. METHODS AND PATIENTS: We report
      on 225 AEG patients undergoing primary resection in our unit (1986-2000) with a
      special focus on perioperative morbidity, mortality, and long-term prognosis
      under consideration of the AEG type (Siewert classification) and operative
      procedure performed (subtotal esophagectomy with proximal gastric resection in
      AEG I, total gastrectomy with distal esophageal resection in AEG II and AEG III).
      RESULTS: Types I, II, and III carcinomas were found in 32%, 42%, and 26% of the
      patients, respectively, with R(0) resections in 65%, 69%, and 51% ( P=0.039). The
      overall 5-year survival rates were 29%, 31%, and 14% ( P=0.068), respectively; in
      R(0)-resected patients, they were 40%, 41%, and 27% ( P=0.771). In univariate
      analysis, the TNM classification ( P<0.001), R classification ( P<0.001), and
      tumor stage ( P<0.001) were relevant prognostic factors. In multivariate
      analysis, only the R classification ( P=0.003), LN ratio ( P=0.012), and N stage
      ( P=0.027) were independent prognostic factors. In 35 of 177 patients resected
      with curative intent, R(0) resections could not be achieved, mainly because of
      residual tumor in the circumferential plane (22/35=63%). Only in 37% of cases
      (13/35) was the R(1) situation due to exclusive positive oral or aboral resection
      margins. Therefore, in only 7% of all patients resected with curative intent
      (13/177) did the question arise of whether the R(1) resection could have been
      avoided by a different surgical approach. Surgical, pulmonary, and cardiac
      complications were found in 33%, 26%, and 10%, respectively. The mortality within
      30 days was 4%. CONCLUSIONS: Failure of R(0) resection in patients treated with
      curative intent is mostly caused by residual tumor in the circumferential plane.
      Therefore, different surgical approaches with varying oral and aboral resection
      margins are of minor importance for reducing the frequency of R(1) resections.
      Downstaging of tumors by neoadjuvant treatment may increase the R(0) resection
      rate.

PMID- 15168032
TI  - [Effectiveness and results of intraoperative neuromonitoring in thyroid surgery.
      Statement of the Interdisciplinary Study Group on Intraoperative Neuromonitoring
      of Thyroid Surgery].
AB  - Intraoperative neuromonitoring (IONM) has yielded an increasing effect on thyroid
      surgery. During IONM, the recurrent laryngeal nerve is stimulated electrically
      and an acoustically transformed electromyographic signal is derived via either a
      needle electrode placed in the vocalis muscle or an electrode adjusted to the
      intubation tube. The IONM is used for identifying and predicting the function of
      the recurrent laryngeal nerve. Especially under difficult anatomic conditions,
      IONM has proven a valuable tool for identification of recurrent laryngeal nerves.
      This can lead to decreased occurrence of nerve palsy rates, as shown in numerous
      studies. The reliability of the IONM signal (defined as the correlation between
      intraoperative signal interpretation and postoperative vocal cord function) is
      reflected by a specificity as high as 98.2%, as shown by German multicenter
      studies. Thus, normal vocal cord function could be demonstrated postoperatively
      in over 98.2% of patients with intraoperatively unchanged neuromonitoring
      signals. If the neuromonitoring signal changed during operation, 39% of the
      patients suffered from transient vocal cord immobility and 12% had permanent loss
      of vocal cord function.

PMID- 15168033
TI  - [Quality management and strategic consequences of assessing documentation and
      coding under the German Diagnostic Related Groups system].
AB  - INTRODUCTION: The introduction of the German Diagnostic Related Groups (D-DRG)
      system requires redesigning administrative patient management strategies. Wrong
      coding leads to inaccurate grouping and endangers the reimbursement of treatment
      costs. This situation emphasizes the roles of documentation and coding as factors
      of economical success. PURPOSE: The aims of this study were to assess the
      quantity and quality of initial documentation and coding (ICD-10 and OPS-301) and
      find operative strategies to improve efficiency and strategic means to ensure
      optimal documentation and coding quality. METHODS: In a prospective study,
      documentation and coding quality were evaluated in a standardized way by weekly
      assessment. RESULTS: Clinical data from 1385 inpatients were processed for
      initial correctness and quality of documentation and coding. Principal diagnoses
      were found to be accurate in 82.7% of cases, inexact in 7.1%, and wrong in 10.1%.
      Effects on financial returns occurred in 16%. Based on these findings, an
      optimized, interdisciplinary, and multiprofessional workflow on medical
      documentation, coding, and data control was developed. CONCLUSIONS: Workflow
      incorporating regular assessment of documentation and coding quality is required
      by the DRG system to ensure efficient accounting of hospital services.
      Interdisciplinary and multiprofessional cooperation is recognized to be an
      important factor in establishing an efficient workflow in medical documentation
      and coding.

PMID- 15168034
TI  - [Thymus lipoma. A rare entity of the thymus. Case report with special
      consideration of diagnostic imaging].
AB  - This report is on a 37-year-old female patient with an extraordinary large
      intrapleural tumor on the left, macroscopically originating from mediastinal
      structures. The tumor was completely removed via transpleural approach without
      compromising the left lung. It was identified as a thymolipoma with a weight of
      2400 g.

PMID- 15168035
TI  - Gastric emptying, gastric secretion and enterogastrone response after
      administration of milk proteins or their peptide hydrolysates in humans.
AB  - BACKGROUND: The influence of protein fractionation on gastric emptying and rate
      of appearance of their constituent amino acids in peripheral blood remains
      unknown. AIM OF THE STUDY: To examine the influence of the degree of protein
      fractionation on gastric emptying, gastric secretion, amino acid absorption and
      enterogastrone response, after the intragastric administration of complete cow
      milk proteins or their respective peptide hydrolysates in man. METHODS: Six
      healthy males were randomized to receive one of the following four solutions:
      whey whole protein (W), casein whole protein (C), whey peptide hydrolysate (WHY)
      or casein hydrolysate (CAHY). All solutions were matched for volume (600 mL),
      nitrogen content (9.3 g/L), energy density (1069-1092 kJ/L), osmolality (288-306
      mosmol/kg), pH (6.9-7.0) and temperature (37 degrees C). RESULTS: Solutions were
      emptied at similar rates, with mean half-times of (mean +/- SEM) 21.4 +/- 1.3,
      19.3 +/- 2.2, 18.0 +/- 2.5 and 19.4 +/- 2.8 min, for the WHY, CAHY, C and W,
      respectively. The rates of intestinal absorption of water and amino acids were
      similar with the exception of the casein protein solution, for which the speed of
      intestinal amino acid absorption was slower (p < 0.05). The peptide hydrolysates
      elicited about 50% more gastric secretion than the whole protein solutions ( p <
      0.05),which was accompanied by higher glucose-dependent insulinotropic
      polipeptide (GIP) plasma levels during the first 20 min of the gastric emptying
      process. Similar glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) plasma
      responses were elicited by the four solutions. CONCLUSIONS: The rate of gastric
      emptying and the plasma GLP-1 and PYY responses to feeding with cow milk protein
      solutions in humans are independent of the degree of protein fractionation and
      are not altered by small differences in the amino acid composition or protein
      solubility. In contrast, the GIP response is accentuated when milk proteins are
      delivered as peptide hydrolysates.

PMID- 15168036
TI  - Effects of differing phenolic content in dietary olive oils on lipids and LDL
      oxidation--a randomized controlled trial.
AB  - BACKGROUND: Evidence from in vitro studies suggests that antioxidant olive oil
      phenolic compounds can prevent LDL oxidation. However, in vivo evidence in
      support of this hypothesis is sparse. AIM OF THE STUDY: to establish the
      antioxidant effect of olive oils with differences in their phenolic compounds
      content in humans METHODS: A controlled, double blind, cross-over, randomized,
      clinical trial using three similar olive oils with increasing phenolic
      concentration (from 0 to 150 mg/Kg) was conducted in 30 healthy volunteers. Olive
      oils were administered over three periods of 3 weeks preceded by two-week washout
      periods. RESULTS: Urinary tyrosol and hydroxytyrosol increased (p < 0.020), in
      vivo plasma oxidized LDL decreased (p = 0.006), and ex vivo resistance of LDL to
      oxidation increased (p = 0.012) with the phenolic content of the olive oil
      administered. After virgin olive oil administration, an increase (p = 0.029) was
      observed in HDL cholesterol levels. CONCLUSIONS: Sustained consumption of virgin
      olive oil with the high phenolic content was more effective in protecting LDL
      from oxidation and in rising HDL cholesterol levels than that of other type of
      olive oils. Dose-dependent changes in oxidative stress markers, and phenolic
      compounds in urine, were observed with the phenolic content of the olive oil
      administered. Our results support the hypothesis that virgin olive oil
      consumption could provide benefits in the prevention of oxidative processes.

PMID- 15168037
TI  - Further glycogen decrease during early recovery after eccentric exercise despite
      a high carbohydrate intake.
AB  - BACKGROUND: Delayed onset muscle soreness (DOMS) is a well-known phenomenon of
      athletes. It has been reported from muscle biopsies that the rate of muscle
      glycogen resynthesis is reduced after eccentric compared to concentric exercise.
      AIM OF THE STUDY: Try to compensate by a carbohydrate (CHO)-rich diet the
      decelerated glycogen resynthesis after eccentric exercise, measured by magnetic
      resonance spectroscopy. METHODS: Glycogen, phosphocreatine, ATP, and Pi were
      measured in the human calf muscle. Twenty athletes divided into two groups (DOMS
      and CONTROL), reduced glycogen in M. gastrocnemius during two different running
      protocols. Additionally, 12 DOMS subjects performed an eccentric exercise while
      the CONTROL group rested. Subsequently, subjects consumed a CHO-rich diet (> 10
      g/kg body mass/24 h). RESULTS: In both groups, glycogen has been reduced by about
      50%. The first 2 h after exercise, glycogen dropped further (-15.6 +/- 15.7 mmol/
      kg ww) in the DOMS but rose by +18.4 +/- 20.8 mmol/kg ww in the CONTROL group (P
      < 0.001). CONTROL subjects reached resting glycogen within 24 h (137 +/- 47
      mmol/kg ww), while DOMS subjects needed more than one day (91 +/- 23 mmol/kg ww;
      P < 0.001). Pi and Pi/PCr, indicators of muscle injury, rose significantly in the
      DOMS but not in the CONTROL group. CONCLUSION: The diet rich in CHO's was not
      able to refill glycogen stores after eccentric exercise. Glycogen decreased even
      further during the beginning of recovery. This loss, which to our knowledge has
      not been measured before is probably the consequence of muscle cell damage and
      their reparation.

PMID- 15168038
TI  - Validation of a food frequency questionnaire to assess macro- and micro-nutrient
      intake among South Asians in the United Kingdom.
AB  - BACKGROUND: The South Asian population is one of the largest minority ethnic
      groups in the United Kingdom (UK), forming 2.7% of the UK population. Risk of
      diseases such as CHD, NIDDM is high in South Asians and risk of cancer low in
      this population compared both to the native UK population and other migrant
      groups. It is useful to investigate the experience of disease and dietary
      exposures for aetiological clues in South Asians. The FFQ was designed for a
      population-based case-control study of diet and breast cancer. AIMS: To validate
      a food frequency questionnaire (FFQ) to assess macro- and micronutrient intake
      among South Asians in the United Kingdom (UK). METHODS: A one-year long study of
      current diet was conducted using monthly telephone 24-hour recalls followed by
      administration of an interviewer-administered FFQ to ascertain usual diet during
      this period. General practices in the Thames and West Midlands regions, England
      were used to sequentially recruit 100 women from a larger random sample of South
      Asian migrants from general practitioners' patient lists participating as
      controls in a case-control study of diet and breast cancer. RESULTS: A total of
      133 women were invited to achieve the final sample of 100 (76% response rate).
      The proportion of individuals classified by the two dietary assessment methods
      into the same or adjacent quartiles was high ranging from 65% (vitamin A) to 96%
      (protein). Misclassification into opposite quartiles was very low (0 % to 5 %),
      except for vitamin A (10 %). Energy-adjusted Spearman correlation coefficients
      were reasonable for almost all nutrients being highest for protein (0.76), NSP
      (0.71), folate (0.70) and cholesterol (0.69). Correction for within-person
      variation in monthly 24-hour recalls had little effect on the magnitude of the
      nutrient correlations between the FFQ and the 24-hour recalls. Calibration
      coefficients to correct relative risks for nutrient-disease associations were
      above 0.50 for most nutrients indicating that the degree of attenuation
      introduced by the FFQ would be acceptable. CONCLUSIONS: This FFQ was specifically
      designed for South Asian women in the UK. Despite the diversity of diets, the FFQ
      had reasonable validity. The role of diet in breast cancer disease aetiology in
      this population is being assessed with this instrument.

PMID- 15168039
TI  - Comparison of dietary habits in the urban and rural Croatian schoolchildren.
AB  - BACKGROUND: Post-war socio-economic changes in Croatia probably affected dietary
      habits, and dietary data about schoolchildren after the war are missing. AIMS OF
      THE STUDY: The aim of the study was to compare current nutrient intakes and
      dietary behavior between urban and rural schoolchildren in Croatia. METHODS: A
      completely quantified Food Frequency Questionnaire was used. Subjects were 315
      urban and 163 rural schoolchildren. Mean age was 12.5 and 12.6 years in the urban
      and rural area, respectively. RESULTS: Consumption of fast food, soft drinks and
      alcohol was more prevalent and more linked with dietary behavior in the urban
      than in the rural area. In both living areas protein intake was excessive (in the
      urban area 38.1% of subjects and in the rural 36.2% of subjects had protein
      intake higher than 200% RDA). Under 75% RDA/DRI in both living areas was observed
      for vitamin D, folate, calcium and selenium. Micronutrient intakes negatively
      correlated with age in both living areas, but were more pronounced in the urban
      area. CONCLUSION: The urban sample had more adequate energy and nutrient intakes
      which is consistent with prewar findings.

PMID- 15168040
TI  - No difference in platelet activation or inflammation markers after diets rich or
      poor in vegetables, berries and apple in healthy subjects.
AB  - BACKGROUND: High intake of vegetables and fruits is associated with decreased
      risk of coronary heart disease. Part of these cardioprotective effects may be
      mediated via the antithrombotic effects of compounds found in vegetables and
      fruits, such as flavonoids. AIM OF THE STUDY: To study the effects of high and
      low intake of vegetables, berries and apple on platelet function and inflammatory
      markers. METHODS: The study was a randomised, controlled parallel human dietary
      intervention with healthy female and male volunteers (n = 77, 19-52 y). Nineteen
      healthy volunteers served as controls. The volunteers consumed one of four
      strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ
      of vegetables, berries and apple and rich either in linoleic acid (11% of energy,
      en%) or oleic acid (12 en%). Blood and three 24-hour urine samples were collected
      at the beginning and at the end of the study period for analyses of various
      markers of platelet function and inflammation. RESULTS: No differences between
      the treatment groups were seen in platelet count or volume, markers of platelet
      activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide,
      protein kinase C activity, urinary 2,3-dinor-thromboxane B2 excretion, plasma P
      selectin), plasma intercellular adhesion molecule-1, sensitive C-reactive
      protein, or antiphospholipid antibodies. CONCLUSIONS: The results indicate that
      in healthy volunteers 6-week diets differing markedly in the amounts of
      vegetables, berries and apple do not differ in their effects on platelets or
      inflammation.

PMID- 15168041
TI  - Differential fermentation of glucose-based carbohydrates in vitro by human faecal
      bacteria--a study of pyrodextrinised starches from different sources.
AB  - BACKGROUND: Pyrodextrins, modified starches produced by heat/acid treatment, have
      been used extensively in the paper industry. Recently, pyrodextrinisation has
      been recognised as a way of producing a "resistant starch" that is water-soluble
      and has non-starch linkages. However, a full characterisation of the fermentation
      properties of pyrodextrins has not been reported. AIM OF THE STUDY: To evaluate
      the effect of pyrodextrinisation on the fermentation characteristics of starches,
      prepared from Venezuelan crops, in a simple in vitro model of the human colon.
      METHODS: Potato, lentil and cocoyam pyrodextrins were produced using heat (140
      degrees C for 3 h) and hydrochloric acid as catalyst (1.82 g/kg starch). Then,
      both native and modified starches were pre-digested with pepsin and pancreatic
      enzymes and their resistant components fermented anaerobically using human faeces
      as inocula for 24 h. Short-chain fatty acids (SCFA), pH, residual starch and
      carbohydrate in the cultures were measured. RESULTS: More than 69% of initial
      carbohydrate disappeared from both pre-digested native and pyroconverted starch
      cultures. More than 6.8 and 10.0 mmol net SCFA per gram carbohydrate were
      produced from pre-digested native and pyrodextrinised starches, respectively. In
      cultures of predigested pyrodextrins, the molar ratio for propionate doubled,
      whereas the ratio of acetate decreased by 25% when compared with pre-digested
      native starches. The ratio of butyrate did not change. CONCLUSIONS: The mechanism
      for the change in SCFA profile is unclear, but may be related to solubility
      and/or presence of nonstarch linkages. The presence of these bonds may modify the
      accessibility/affinity of bacterial enzymes to the modified starch structure.

PMID- 15168043
TI  - Surgical management of entero and colocutaneous fistulae in Crohn's disease: 17
      year's experience.
AB  - BACKGROUND AND AIMS: Fistulous disease is common in Crohn's disease, and entero-
      and colocutaneous fistulae are particularly debilitating and difficult to manage.
      We present the results of surgical management of these fistulas. PATIENTS AND
      METHODS: Retrospective chart review of all 51 patients with Crohn's disease (56
      surgical procedures) undergoing surgery for cutaneous fistulae between 1983 and
      2000. RESULTS: Previous surgery for Crohn's disease had been carried out in 43
      patients (84%). The fistula site was enterocutaneous in 36 patients (64%),
      colocutaneous in 12 (21%), and anastomotic in 8 (14%); 9 patients (16%) also had
      associated enteroenteric fistulas. The onset of the fistula followed abscess
      drainage in 15 (27%) and occurred at the site of recurrent disease in 41 (73%).
      Forty patients (71%) initially underwent conservative management prior to
      surgery; 16 (28%) underwent surgery directly. Surgical procedures were: 25
      ileocolic resections, 8 stoma revisions with resection, 8 small bowel resections
      7 subtotal colectomies, 4 partial colectomies, 3 proctocolectomies, and one
      fistula tract excision. Mean total length of stay was 18 days (postoperative 10.7
      days). Six (11%) patients had eight postoperative complications. Mean follow-up
      was 48.6 months (range 3-187). Recurrence as defined by either clinical
      examination or reoperation was documented in nine fistulas (16%), with a mean
      time to recurrence of 27 months. CONCLUSION: Entero-and colocutaneous fistulae
      usually occur from a site of active disease. Surgical management with bowel
      resection, including the fistula, is the preferred method of treatment. Morbidity
      has been low and recurrence rate lower than expected.

PMID- 15168045
TI  - Does any lower gastrointestinal bleeding in patients suffering from hereditary
      hemorrhagic telangiectasia (Osler-Weber-Rendu) necessitate a full colonic
      visualization?
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) (the Osler-Weber-Rendu
      syndrome) is a rare autosomal dominant disease characterized by telangiectasias
      and arteriovenous malformations of the upper and lower respiratory tract,
      gastrointestinal tract, skin and central nervous system. Several previous reports
      have documented the appearance of a concomitant neoplasm in patients with this
      syndrome. AIMS: To study the occurrence and the clinical characterization of
      colonic neoplasm in patients with HHT. METHODS: We retrospectively reviewed the
      computerized database of the Hadassah University Hospitals (Jerusalem, Israel)
      for all patients with the diagnosis of HHT between January 1st, 1980 and July
      30th, 2002. Cases of neoplasm were documented by review of medical charts and
      pathology reports. RESULTS: Six of the 24 patients developed malignancy. Three of
      the cases had extra colonic malignancy (melanoma in two patients and
      adenocarcinoma of urinary bladder in one patient) and three patients had
      adenocarcinoma of the colon. An additional three patients developed multiple
      colonic polyps (one patient had melanoma and one patient had adenocarcinoma of
      urinary bladder). CONCLUSIONS: HHT may be associated with the development of
      colonic adenocarcinoma and polyps. Therefore, in patients with HHT who present
      with new-onset anemia or gastrointestinal bleeding a lower gastrointestinal tract
      evaluation should be performed, even if their blood loss is suspected to be a
      manifestation of gastrointestinal HHT.

PMID- 15168046
TI  - Ileocecal reservoir reconstruction after total mesorectal excision: functional
      results of the long-term follow-up.
AB  - BACKGROUND: The aim of this study is to obtain functional results of the long
      term follow-up after TME and ileocecal interposition as rectal replacement.
      METHODS: The study included patients operated on between March 1993 and August
      1997 who received an ileocecal interposition as rectal replacement. Follow-up was
      carried out 3 and 5 years postoperatively. For statistical analysis, the paired t
      test, rank test (Wilcoxon), and chi-square or Fisher's exact test were applied;
      level of significance, P<0.05. RESULTS: Forty-four patients were included in the
      studies. Of these, five were not available and four patients could not be
      evaluated (dementia 1, radiation proctitis 1, fistula 1, pouchitis 1). Seventeen
      patients died during the observation period; 12 died of the disease. Recurrence
      of the disorder occurred in 2 of 35 patients (5.7%); 26 and 18 patients, 3 and 5
      years postoperatively, respectively remained in the study. At 5 years, 78% of the
      patients were continent; mean stool frequency was 2.5+/-1.6 per day. CONCLUSIONS:
      Functional results and subjective assessment of ileocecal interposition were
      constant at 3 and 5 years postoperatively. If construction of a colonic J-pouch
      is not possible due to lack of colonic length, especially after prior colonic
      resections, the ileocecal interpositional reservoir may offer an alternative to
      rectal replacement.

PMID- 15168047
TI  - Preoperative angioembolisation for life-threatening haemorrhage from Wilms'
      tumour: a case report.
AB  - Wilms' tumour is one of the most common abdominal tumours of childhood. Severe
      perirenal bleeding resulting in consumptive coagulopathy and colonic obstruction
      are rare complications of Wilms' tumour. We present a case report of one patient
      with these two complications, their successful management with preoperative
      angioembolisation and emergency nephrectomy, and a review of the relevant
      literature.

PMID- 15168048
TI  - Serum hyaluronan as a marker reflecting the severity of cirrhosis and portal
      hypertension in postoperative biliary atresia.
AB  - The majority of patients with biliary atresia (BA) develop progressive liver
      disease and serious complications of portal hypertension, including esophageal
      varices and ascites, despite successful Kasai operation. The aim of this study
      was to evaluate whether serum hyaluronan (HA) reflects the severity of cirrhosis
      and its complications in patients with postoperative BA. Fifty-four postoperative
      BA patients aged 1 to 19 years were recruited into this study. Serum HA was
      determined by ELISA-based assay, and serum HA levels were compared among groups
      of patients according to Child's classification as well as the presence of
      esophageal varices and ascites. Mean serum HA concentration was significantly
      increased in patients with Child C (534.35 +/- 573.02 ng/ml) in comparison to
      patients with Child B (97.67 +/- 104.22 ng/ml, p = 0.002) and Child A (36.27 +/-
      71.41 ng/ml, p < 0.001). Mean serum HA concentration was also significantly
      higher in patients who had ascites or esophageal varices than in those who did
      not suffer from these complications. Furthermore, patients who had variceal
      hemorrhage had significantly higher mean serum HA levels than those without
      bleeding. Thus, serum HA levels may reflect the severity of cirrhosis and its
      complications, and may be useful in monitoring the clinical outcomes of patients
      with postoperative BA.

PMID- 15168049
TI  - Mesenteric cyst infected with non-typhoidal salmonella infection.
AB  - Although extra-intestinal non-typhoidal Salmonella infections are common in
      developing countries, infection of the mesenteric cyst with Salmonella
      enteritidis is an extremely rare occurrence. Review of the English literature has
      revealed one report up to this date. The case of a 4-year-old boy with a
      mesenteric cyst infected with Salmonella enteritidis is presented.

PMID- 15168050
TI  - Outcome of submucosal injection of different sclerosing materials for rectal
      prolapse in children.
AB  - Parasitic infestations, mainly enterobiasis and amoebiasis, and poor toilet
      training practices are commonly associated with rectal prolapse in developing
      countries. Injection sclerotherapy is one of the commonly used modalities for
      treating partial rectal prolapse in children. Various materials are available for
      such injection, but each has its advantages and complications. Comparing
      different materials used in the treatment of such pathology form the basis of
      this study trying to define the best material with the least complications. Data
      records of 130 children with partial rectal prolapse referred to the Department
      of Pediatric Surgery at Al Galaa Teaching Hospital, Cairo, over a 3-year period
      were analyzed. Their ages ranged from 6 months to 12 years (mean 6.14 years +/
      3.4). Forty-five patients (3 5%) responded to conservative treatment, and 85
      patients (65%) required injection sclerotherapy and were divided into three
      groups: Group 1 (35 patients) was injected with 98% ethyl alcohol, group 2 (22
      patients) was injected with phenol in almond oil 5%, and group 3 (28 patients)
      was injected with Deflux (Q-Med, Uppsala, Sweden). The follow-up period ranged
      from 2 months to 3 years; clinical data and all complications were recorded.
      Submucosal injection of the three sclerosing materials showed no mortality in
      this series, but in group 1, seven had recurrence on short-term follow-up that
      required reinjection, and long-term follow-up in this group showed a recurrence
      rate of 11% (four patients), plus two patients had mucosal sloughing and one girl
      developed a rectovaginal fistula. Group 2 showed abscess formation and mucosal
      sloughing in four patients (18%), and two developed perianal fistula. Group 3
      showed immediate postoperative prolapse in two cases that ameliorated
      spontaneously. No patients had mucosal ulceration or abscess formation, and long
      term follow-up showed no recurrence. Deflux had the lowest complication rate with
      no recurrence on long-term follow-up. Phenol in almond oil 5% injection should
      not be used for treating such conditions because of its high complication rate.
      Alcohol is commercially cheap and available and should be considered an
      alternative for Deflux.

PMID- 15168052
TI  - Uncommon cause of sinus thrombosis following closed mild head injury in a child.
AB  - OBJECT: Sinus thrombosis following a closed mild head injury is rare. A case of
      dural sinus thrombosis following a mild closed head injury due to an uncommon
      cause is reported. METHODS: A 7-year-old child presented with GCS 15 after a road
      traffic accident. CT revealed an occipital fracture. Ten days later the child
      developed signs of increased intracranial pressure. An MR venogram at this time
      revealed thrombosis of the transverse sinus with hypoplasia of the contralateral
      transverse and sigmoid sinuses. The patient's anitiphospholipid antibody titres
      were elevated. The patient was treated with anticoagulants and improved.
      CONCLUSIONS: The role of inherited and acquired procoagulant factors in the
      aetiology of sinus thrombosis is increasingly being recognized. When a patient
      presents with sinus thrombosis after a closed mild head injury, it is necessary
      to investigate for the presence of risk factors for thrombophilia as it has
      implications for the long-term management of the patient.

PMID- 15168051
TI  - Indication for and surgical outcomes of the distraction method in various types
      of craniosynostosis. Advantages, disadvantages, and current concepts for surgical
      strategy in the treatment of craniosynostosis.
AB  - BACKGROUND: Various surgical techniques for the treatment of craniosynostosis
      using distraction devices have been described over the last few years and we have
      applied these procedures in seven patients with varying types of
      craniosynostosis. The aim of this report is to clarify the advantages and
      disadvantages of these surgical methods and to discuss current concepts for the
      surgical strategy in the treatment of craniosynostosis. MATERIAL AND METHODS:
      From January 2001 to March 2003, 25 patients with craniosynostosis were examined.
      Among them, 7 patients, 5 with Apert syndrome, 1 with Crouzon disease, and 1 with
      multiple-synostosis, underwent surgical treatment using the distraction method
      with internal distraction devices, according to our treatment strategy for
      craniosynostosis. All patients underwent preoperative and postoperative
      evaluations, which included the patient's neurological state, developmental
      quotient (DQ), and three-dimensional CT (3D-CT). RESULTS: The timing of the
      procedures undertaken was between the ages of 1 year 5 months and 12 years 6
      months (mean age 4 years 11 months). Five patients had received previous
      treatment and this procedure was used as a secondary operation. Postoperative
      distraction distances varied from 7 to 20.5 mm (mean distraction distance: 14
      mm). Satisfactory cranial volume expansion and aesthetically pleasing
      morphological states were achieved in all cases. Regarding complications, one
      patient required re-operation because of dislocation of the device and skin
      erosion caused by infection around the penetrated wound. Finally, in a second
      patient a distortion of the device occurred, but no re-operation was needed.
      CONCLUSION: The advantage of the distraction method is its applicability for
      Toddler or Elder Children Calvarial Reconstruction to correct cosmetic and
      functional problems. One disadvantage is the difficulty in using it for Infantile
      Calvarial Normalization because of thin calvarial bones and the necessity for re
      operation to remove the device, which may result in it becoming a "fixation
      procedure," essentially contraindicated for the fast-developing brain and
      calvarias. However, the efficacy of this procedure is that the many advantages
      outweigh the disadvantages as sufficient calvarial expansion and good results
      using the distraction method, especially in toddler and elder children age
      groups, can be achieved.

PMID- 15168053
TI  - Minimizing blood transfusions in the surgical correction of coronal and metopic
      craniosynostosis.
AB  - OBJECTIVE: The current study was performed to determine the rate of allogeneic
      blood transfusion for coronal and metopic craniosynostosis surgery done by two
      experienced pediatric neurosurgeons and to identify factors associated with a
      need for transfusion. METHODS: First operations for coronal and metopic
      craniosynostosis correction in children from 1996 to 2002 were reviewed
      retrospectively. For analysis, the primary endpoint was defined as either the
      receipt of a blood transfusion or a postoperative Hb level below 70 g/l, even if
      no blood was transfused. Univariate and multivariate analyses were done to
      examine the relationship of attaining the primary endpoint to extent of surgery,
      surgeons, surgery time, preoperative hemoglobin, craniosynostosis type, weight,
      and age. RESULTS: Thirty-two patients were operated on: 17 with unicoronal; 9
      with bicoronal, and 6 with metopic craniosynostosis. Median age at operation was
      7.5 months. Blood transfusion rates were 0% for unicoronal, 44% for bicoronal,
      and 33% for metopic synostosis operations. Logistic regression revealed that the
      best predictor of having a postoperative hemoglobin level of <70 g/l or receiving
      a blood transfusion was the extent of surgery (beta=1.59, SE(beta)=0.57). The
      odds of reaching the primary endpoint for extensive surgery over basic surgery
      was 4.9 [95%CI=(1.6,15.0)]. Once extent of surgery was accounted for in the
      model, no other covariates significantly improved the model. CONCLUSIONS: Low
      transfusion rates were achieved in primary operations for coronal and metopic
      craniosynostosis using simple intraoperative techniques and by accepting a low
      postoperative hemoglobin level.

PMID- 15168055
TI  - Zig-zag bicoronal scalp incision for cranio-facial cases in paediatric
      neurosurgery.
AB  - TECHNIQUE: We present the use of a zig-zag bicoronal scalp incision for cranial
      facial cases in paediatric neurosurgery. CONCLUSION: The authors believe that
      this technique leads to improved cosmesis, especially when the hair is wet.

PMID- 15168056
TI  - Increase in circulating endothelial progenitor cells after aortic aneurysm
      repair.
AB  - Rapid endothelialization of prosthetic vessels is essential to avoid fatal
      complications. We hypothesized that there may be mobilization of endothelial
      progenitor cells (EPCs) in patients who received aortic aneurysm repair, and
      measured the number of CD34-expressing EPCs (CD34(+) cells) in these patients.
      Blood samples were taken preoperatively, 6, 24, and 48 h, and 7 days after
      surgery in 13 patients with aortic aneurysm. Samples were also obtained from ten
      age-matched control subjects. The number of CD34(+) cells in the peripheral blood
      was quantified by flow cytometry. The levels of serum vascular endothelial growth
      factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit.
      Baseline CD34(+) cell counts in the peripheral blood showed a tendency to be
      lower in patients with aortic aneurysm compared with healthy control subjects.
      The number of CD34(+) cells did not change over 48 h after aortic aneurysm
      repair; however, it had doubled by the 7th day. On the other hand, the baseline
      serum VEGF levels did not differ between the patients and control subjects. The
      VEGF levels increased gradually after vascular repair with a significant
      elevation after 48 h, which was followed by an increase in CD34(+) cell counts.
      In conclusion, the circulating CD34(+) cell counts and serum VEGF levels are
      increased after vascular prosthesis replacement in patients with aortic aneurysm,
      which might contribute to the rapid endothelialization of prosthetic vessels.

PMID- 15168054
TI  - Pediatric embryonal tumor with epithelial immunophenotype showing absence of
      hSNF5/INI1 expression.
AB  - CASE REPORT: A case of a histologically unclassified brain tumor in a 32-month
      old boy is reported. He presented with vomiting, appetite loss, and right motor
      weakness. MR images revealed a huge mass in the left frontoparietal region that
      was enhanced after the administration of Gd-DTPA. The mass was removed three
      times because of its recurrence. RESULTS: Histologically, the tumor was composed
      largely of small-undifferentiated round cells without any patterns of
      differentiation. Immunohistochemically, the tumor cells were positive for
      cytokeratin and focally for epithelial membrane antigen (EMA). Glial fibrillary
      acidic protein (GFAP), S-100 protein and neuronal markers were negative. Electron
      microscopic investigations demonstrated no evidence of specific differentiation.
      MIB-1 staining index was 10-40%. The origin of the tumor was not detected.
      Expression of the hSNF5/INI1 of this tumor was not detected by reverse
      transcription-polymerase chain reaction (RT-PCR). The patient has been in a good
      condition for 7 years after the first operation. CONCLUSIONS: Based on the
      immunohistochemical findings, the tumor was descriptively diagnosed as an
      embryonal tumor with an epithelial immunophenotype. The hSNF5/INI1 gene has
      recently been reported to act as a tumor suppressor in atypical teratoid/rhabdoid
      tumors. The hSNF5/INI1 gene may lead to tumorigenesis in this case.

PMID- 15168057
TI  - Usefulness of predischarge exercise electrocardiographic testing in detecting the
      late patency status of the infarct-related artery.
AB  - Predischarge exercise electrocardiographic testing (PEET) represents a widely
      accepted clinical tool for prognostic and functional assessment of patients who
      experience an uncomplicated acute myocardial infarction (AMI). However, there are
      no data suggesting any relation between PEET results and patency status of the
      infarct-related artery (IRA). The aim of this study was to investigate whether ST
      and/or QT-dispersion (QTD) changes induced by a low-level PEET, after
      uncomplicated ST-elevation AMI, are related to the late patency status of the
      IRA. We prospectively evaluated 61 consecutive patients who had suffered a first
      uncomplicated ST-elevation AMI. All of them successfully carried out four stages
      of the modified Bruce protocol exercise testing before discharge, and thereafter
      were subjected to coronary angiography. Exercise-induced ST elevation and QTD
      shortening were found significantly more frequently in patients with persistently
      occluded IRA, as compared to patients with patent IRA (ST elevation 65% vs 27%, P
      = 0.006; QTD shortening 80% vs 29%, P < 0.0001). The coexistence of the two
      variables predicted the presence of occluded IRA with a positive predictive value
      of 75%, whereas the absence of both predicted the patency of IRA with a negative
      predictive value of 100%. These results indicate that ST-elevation and QT
      dispersion changes induced by a predischarge exercise testing after a first ST
      elevation AMI may effectively predict the late patency status of the infarct
      related artery.

PMID- 15168058
TI  - Does claudication affect the development of coronary collaterals?
AB  - Atherothrombosis is a generalized disease process that affects large- and medium
      diameter arteries throughout the arterial tree. In this study, we aimed to
      evaluate the correlation between collaterals in different vascular beds. Patients
      who had undergone digital subtraction angiography for symptomatic lower extremity
      peripheral arterial disease and coronary angiography after an acute anterior
      myocardial infarction (MI) were compared with a control group composed of those
      patients who were hospitalized for acute anterior MI and underwent coronary
      angiography but had no claudication and had an ankle-brachial index of greater
      than 0.9 in both legs. In claudicants, stenosis in the left anterior descending
      artery (LAD) (90.3 +/- 17.5 vs 78.6 +/- 13.8, P = 0.005) was greater compared
      with the patients without claudication. The collaterals to the LAD (88% vs 37.5%,
      P = 0.001) and the collateral grades (1.7 +/- 0.7 vs 0.7 +/- 0.9, P = 0.001) were
      higher in the patients with claudication compared with those without
      claudication. A previous history of angina (52.2% vs 16.3%, P = 0.001),
      claudication (39.1% vs 4.6%, P = 0.001), and peripheral collaterals (45.7% vs
      6.9%, P = 0.001) were higher in the patients with coronary collaterals than in
      those without. The factors affecting the development of coronary collaterals were
      claudication [relative risk (RR): 8.8; 95% confidence interval (CI): 2.1-39.8],
      peripheral collaterals (RR: 1.1; 95% CI: 1.1-1.3), and LAD stenosis (RR: 1.2; 95%
      CI: 0.03-29.1). Our results suggest that the presence of collateralization or
      angiogenesis in one vascular bed highly predicts collateralization in another
      arterial bed.

PMID- 15168059
TI  - The clinical and surgical features of right-sided intracardiac masses due to
      echinococcosis.
AB  - Right-sided cardiac echinococcosis shows special clinical and surgical features
      beyond the rareness of echinococcosis in this position, leading to serious and
      life-threatening complications. We examined our cardiac hydatid cyst patients,
      retrospectively, and report our experience of the surgical treatment of right
      sided cardiac hydatid cysts. Between 1985 and 2000, seven patients were
      transferred to our department from the cardiology department with a diagnosis of
      cystic cardiac masses which were highly suspected of being hydatid cysts. Two
      were males and 5 were females. In 3 patients the hydatid cyst was located in the
      right ventricle, and one was in the right atrium. The mean age of the patients
      was 37 years (ranging from 12 to 60 years). One patient had preoperative
      pulmonary emboli. In all right-sided cardiac echinococcosis patients,
      cardiopulmonary bypass was used. All cysts were cleaned after quilting the cystic
      cavities, and daughter cysts were removed carefully. The cavities were closed
      with purse-string sutures. Postoperatively, one patient had pulmonary emboli. In
      all patients, mebendazole was administered postoperatively. When a right-sided
      cardiac hydatid cyst is diagnosed, early surgical treatment should be performed
      under open-heart surgery conditions. During the operation, a single cannula in
      the superior vena cava should be used until fibrillation, and after clamping, the
      cannula for the pulmonary artery inferior vena cava should be inserted.

PMID- 15168060
TI  - Taurine prevents beta-glycerophosphate-induced calcification in cultured rat
      vascular smooth muscle cells.
AB  - Vascular calcification is an ectopic calcification that commonly occurs in
      atherosclerosis. Because taurine was previously shown to protect against
      cardiovascular diseases, the effect of taurine on vascular calcification was
      evaluated in calcified vascular smooth muscle cells (VSMCs) of rat in vitro in
      the present study. Osteoblastic differentiation, calcification, and proliferation
      in VSMCs were detected in the presence and absence of taurine. Alkaline
      phosphatase (ALP), cellular calcium content, and (45)Ca accumulation were
      measured as the indicators of osteoblastic differentiation and calcification.
      Incubation of VSMCs with Beta-glycerophosphate for 10 days induced an osteoblast
      like morphological change. The activity of ALP was enhanced. Calcium content and
      (45)Ca uptake were increased in these cells. Calcification of these VSMCs was
      demonstrated with Beta-glycerophosphate treatment. In association with these
      alterations, cell proliferation, detected by cell counting, [(3)H]thymidine
      ([(3)H]TdR), and [(3)H]leucine ([(3)H]Leu) incorporation, was also increased in
      these calcified VSMCs. Taurine at 20 mmol/l decreased calcium content, (45)Ca(2+)
      uptake, and ALP activity both after early and late treatment, in which a
      reduction of the cell count, [(3)H"]TdR, and [(3)H]Leu incorporation of calcified
      VSMCs was also noted. Compared with the calcified group, morphological changes in
      the VSMCs of the early-treated group were deferred. These results demonstrated
      that calcification of VSMCs could be alleviated by taurine. Taurine treatment
      appeared to be more beneficial when the treatment was started earlier.

PMID- 15168061
TI  - Oral taurine supplementation prevents fructose-induced hypertension in rats.
AB  - Taurine is known to have antihypertensive and lipid-lowering effects in some
      experimental models and patients. On the other hand, intracellular free calcium
      and magnesium play important roles in regulating the tonus of blood vessels and
      insulin sensitivity. We examined the effect of oral taurine supplementation on
      blood pressure, serum metabolic parameters, and platelet cytosolic free calcium
      ([Ca(2+)](i)) and magnesium ([Mg(2+)](i)) concentration in fructose-fed Sprague
      Dawley rats. Systolic blood pressure and platelet [Ca(2+)](i) were significantly
      higher in rats fed a 60% fructose diet. Oral taurine supplementation (1% in
      drinking water) completely prevented the elevation of blood pressure and an
      increase in platelet [Ca(2+)](i), but exacerbated hyperinsulinemia,
      hypertriglyceridemia, and a decrease in platelet [Mg(2+)](i). In conclusion,
      taurine may ameliorate fructose-induced hypertension in rats by preventing an
      increase in intracellular free calcium concentration. The blood pressure-lowering
      effect of taurine appeared to be independent from its effect on glucose and lipid
      metabolism in this model.

PMID- 15168063
TI  - Plasma fibrinogen and its association with cardiovascular risk factors in
      apparently healthy Japanese subjects.
AB  - Recent evidence has shown the association of increased plasma fibrinogen levels
      with subsequent coronary heart disease or stroke. Fibrinogen is an acute-phase
      inflammatory reactant as well as a clotting factor. The authors investigated an
      association between fibrinogen levels and cardiovascular risk factors in
      apparently healthy Japanese subjects, while considering C-reactive protein (CRP)
      levels, a marker of the inflammatory status. Plasma fibrinogen and serum CRP from
      2 706 participants in an annual mass screening examination, held in Matsukawa,
      Nagano, Japan were measured. A total of 2 355 subjects (816 men and 1 539 women)
      were analyzed after excluding individuals with a history of diabetes mellitus,
      heart disease, or stroke. Plasma fibrinogen was strongly correlated with CRP
      levels. After adjusting the CRP levels, fibrinogen was positively associated with
      age, smoking status, total cholesterol, and hemoglobin A(1c) (HbA(1c)) in men,
      and with age, total cholesterol, and HbA(1c) in women. On the other hand, high
      density lipoprotein (HDL) cholesterol was a strong negative correlate of
      fibrinogen in both genders. Fibrinogen levels also tended to be associated
      positively with body mass index in both genders and negatively with exercise
      habits in men. The present multiple regression analysis has shown that plasma
      fibrinogen levels are correlated with conventional cardiovascular risk factors
      even after adjusting for the CRP levels. Persons with cardiovascular risk factors
      tended to have higher fibrinogen levels, suggesting that all elevated plasma
      fibrinogen concentration in those with risk factors may further increase the risk
      of the development of atherothrombosis and subsequent cardiovascular disease
      through the blood coagulation system.

PMID- 15168062
TI  - Block of HERG current expressed in HEK293 cells by the Na+-channel blocker
      cibenzoline.
AB  - A Na(+)-channel blocker, cibenzoline, blocks the delayed rectifier potassium
      current ( I(k)), but its detailed action on the rapidly activating component (
      I(kr)) of I(k) encoded by the human ether-a-go-go-related gene ( HERG) has not
      been clarified. We examined the effects of cibenzoline on stably expressed HERG
      current in HEK293 cells recorded by the patch-clamp technique of whole-cell
      configuration. Cibenzoline blocked HERG current expressed in HEK293 cells with
      IC(50) = 3.7 +/- 0.963 micro M and Hill coefficient = 0.74 +/- 0.12. Voltage
      depended activation was shifted in a negative direction by cibenzoline. No block
      or minor block was induced at test depolarization of -40 to -30 mV, and the block
      increased with depolarization reaching a plateau at 0 mV without a further
      increase at positive voltages. Voltage-dependent activation of HERG currents
      became faster at negative test voltages but there were no changes at positive
      voltages after cibenzoline. No frequency-dependent block of HERG tail current by
      cibenzoline after equilibration was noted between 1.33 and 0.2 Hz. Steady-state
      inactivation of the HERG current was shifted in a negative direction by
      approximately 8 mV but the time constants of fast inactivation were little
      affected by cibenzoline. Cibenzoline blocks the I(kr)-like current reconstituted
      by HERG clone transfection with an IC(50) value comparable to therapeutic
      concentrations. Cibenzoline has a preferential affinity, at least, to the open
      state of the HERG channel with a rapid access to the binding site.

PMID- 15168064
TI  - Candida parapsilosis endocarditis that emerged 2 years after abdominal surgery.
AB  - A 22-year-old man was hospitalized after 3 months of persistent fever and
      malaise. He had undergone abdominal surgery 24 months before admission.
      Echocardiography demonstrated two mobile pedunculated masses in the right
      ventricle. Multiple blood cultures were positive for Candida parapsilosis. After
      4 weeks of miconazole treatment, the two masses were excised via a right
      atriotomy incision and the transtricuspid value approach. Histological
      examination revealed that they were fungal vegetation. Antifungal agents were
      continued for 1 year after surgery. The patient has remained well with no further
      symptoms for 3 years. This case suggests the necessity for careful evaluation of
      past history to avoid diagnostic delay in fungal endocarditis.

PMID- 15168065
TI  - Pacemaker implantation in patients with persistent left superior vena cava.
AB  - Implantation of a permanent pacemaker system is most commonly performed by
      puncturing the left subclavian vein and introducing the pacemaker lead(s) through
      the superior caval vein to the right atrium and/or ventricle. Occasionally, a
      persistent left superior caval vein is encountered peroperatively, complicating
      the procedure. This article describes three such patients and provides a review
      of the literature regarding one of the most common anomalies of the thoracic
      vessels.

PMID- 15168066
TI  - Abdominal aortic aneurysm related to Takayasu arteritis during pregnancy.

PMID- 15168067
TI  - Pulmonary artery aneurysm in Behcet's disease: a case report.
AB  - The pulmonary artery is the second most common site of arterial involvement in
      Behcet's disease. A 32-year-old man presented with bilateral ankle edema,
      abdominal discomfort, and hemoptysis. He had a history of recurrent oral and
      genital aphthous ulcerations for 1 year. The diagnosis of Behcet's disease was
      made on the basis of the criteria published by the International Study Group for
      Behcet's Disease. His chest X-ray revealed left hilar enlargement. A helical
      computed tomography (CT) scan showed a pulmonary aneurysm with intramural
      thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment
      with colchicine and cyclophosphamide was given for 24 months, and helical
      thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm
      was reduced by treatment. Helical CT could be used in Behcet's disease for the
      diagnosis and follow-up of pulmonary involvement.

PMID- 15168068
TI  - Three digestive movements in Hydra regulated by the diffuse nerve net in the body
      column.
AB  - The mammalian digestive tract undergoes various digestive movements such as
      peristalsis and segmentation movement. How those digestive movements and the
      underlying mechanisms appeared in evolution remains unraveled. A widely accepted
      view has been that, early in evolution, the digestive process was static based
      upon diffusion, and later it became dynamic involving digestive movements. Here,
      we report digestive movements which occur in Hydra, a member of the phylum
      Cnidaria. We find that the body column of Hydra undergoes a series of movements
      when fed with Artemia. Comparison of the movements to those in mammals showed
      similarities in appearance to esophageal reflex, segmentation movement, and
      defecation reflex. When nerve cells were eliminated, polyps showed only a weak
      segmentation movement, demonstrating that the diffuse nerve net in the body
      column of Hydra primarily regulates the movements just as the netlike enteric
      nervous system does in mammals. Elimination of both secretory gland cells and
      nerve cells resulted in the complete loss of movement, suggesting that the gland
      cells are involved in the weak movement. Overall, these observations suggest that
      the digestive process in Hydra is dynamic and that the diffuse nerve net
      regulates the digestive movements as a primitive form of enteric nervous system.

PMID- 15168069
TI  - [Combined glaucoma-cataract surgery].
AB  - Trabeculectomy is the most commonly used glaucoma procedure for combined glaucoma
      cataract surgery. The results are, however, challenged by rather frequent
      exudation of fibrin into the auterior chamber. Therefore, two separate procedures
      can be recommended if there is no urgent need for a combined glaucoma-cataract
      operation. The other glaucoma procedures that were described in combination with
      cataract surgery are trabeculotomy, deep sclerectomy, viscocanalostomy,
      trabecular aspiration, and laser trabecular ablation. The IOP lowering effect of
      these procedures seems somewhat less effective. However, there is also a lower
      complication rate. In combined procedures, a separate temporal clear cornea
      approach for phacoemulsification is superior to a one-site approach. Nuclear
      expression techniques and corneoscleral incisions should no longer be used in
      combined glaucoma-cataract surgery.

PMID- 15168070
TI  - [36-year old female patient with central retinal hemorrhage].

PMID- 15168072
TI  - Amplification of plant genomic DNA by Phi29 DNA polymerase for use in physical
      mapping of the hypermethylated genomic region.
AB  - Plant genomes contain a heavily methylated region in which cytosines are
      methylated in both the symmetrical and asymmetrical sequences. The physical
      mapping of such a hypermethylated region is difficult because many restriction
      enzymes are sensitive to methylated cytosine residues in their recognition sites.
      The Phi29 DNA polymerase provides an efficient and representative amplification
      of the genomic DNA that is methylation-free. Using this amplified genomic DNA, we
      were able to show that a heavily methylated genomic DNA region becomes amenable
      to physical mapping with any restriction enzymes. This protocol will be
      especially useful for analysis of the heavily methylated region of plant genomes.

PMID- 15168071
TI  - Use of the tobacco feedback-insensitive anthranilate synthase gene (ASA2) as a
      selectable marker for legume hairy root transformation.
AB  - The feedback-insensitive anthranilate synthase ( ASA2) cDNA--isolated from a 5
      methyltryptophan (5MT)-resistant tobacco cell line--driven by the CaMV 35S
      promoter or 606 bp of the native ASA2 promoter, was introduced into the forage
      legume plant Astragalus sinicus or soybean ( Glycine max), using Agrobacterium
      rhizogenes strains DC-AR2 or K599, respectively. Hairy roots of A. sinicus
      transformed with 35S-ASA2 but not 606- ASA2 could be directly selected using 20
      75 micro M 5MT. ASA2 mRNA was expressed in all A. sinicus lines selected with
      5MT, but nptII mRNA was expressed only in some lines even though the gene was
      present. Free tryptophan was increased 8- to 26-fold in A. sinicus and 3- to 6
      fold in soybean (selected with kanamycin). An HPLC method was used to measure
      anthranilate synthase (AS) activity since there was a fluorescent compound or
      compounds present in the soybean hairy root extracts. The transformed soybean
      hairy roots contained more feedback-resistant AS activity, showing that there is
      interaction of the tobacco ASA2 alpha-subunit with the soybean beta-subunit to
      form an active enzyme. Soybean hairy roots that express ASA2 also exhibit 5MT
      resistance. These results demonstrate that the tobacco feedback-insensitive ASA2
      gene can be used as a selectable marker for transformation of the legume A.
      sinicus.

PMID- 15168074
TI  - Chemical nursing: phytosulfokine improves genetic transformation efficiency by
      promoting the proliferation of surviving cells on selective media.
AB  - The relative growth rate of plant cells in vitro is considerably affected by
      initial cell density. This troublesome effect has interfered with the
      establishment of efficient plant cell culture systems, especially when only a
      small number of cells are expected to survive, such as in the genetic
      transformation of cells under antibiotic selection. To improve the recovery of
      antibiotic-resistant cells, we examined the use of the peptide plant hormone
      phytosulfokine (PSK), which has been shown to promote cellular growth and
      development in vitro. The addition of PSK to selective media increased the
      recovery of transformed callus from Agrobacterium-infected carrot hypocotyl
      explants from 7% to 39%, which is more than a fivefold improvement over the
      control. Most calluses developed into normal plantlets with cotyledons and
      primary roots and, eventually, formed foliage leaves. Thus, chemical nursing
      using PSK shows promise as a tool for basic research in plant biology and
      biotechnological applications.

PMID- 15168073
TI  - Chalcone synthase-like gene in the liverwort, Marchantia paleacea var. diptera.
AB  - A chalcone synthase (CHS)-like gene, MpCHSLK1, was isolated from liverwort,
      Marchantia paleacea var. diptera. Phylogenetic analysis revealed that MpCHSLK1 is
      closely related to stilbene synthase of the whisk fern, Psilotum nudum. Southern
      blot analysis using an MpCHSLK1 probe revealed that the gene belongs to a small
      gene family. Northern blot analysis indicated that CHS-like genes were expressed
      in either the mother plants or photoautotrophic cells. In photoautotrophic cells,
      the CHS-like genes were expressed light-dependently, and this expression was
      completely inhibited by the photosynthetic electron transport inhibitor, DCMU.

PMID- 15168076
TI  - [Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy:
      criteria of the histopathological evaluation].
AB  - Following surgical resection locally advanced oesophageal carcinomas exhibit a
      bad prognosis and therefore neoadjuvant therapeutic strategies were developed.
      Because success of therapy is associated with the extent of tumor regression in
      this context, the introduction of objective histopathological criteria seems to
      be very important. This study included 67 patients with oesophageal carcinomas
      (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil
      containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24
      cases adenocarcinomas were diagnosed. After completion of therapy, a surgical
      resection and a histopathological examination of the tissue specimens were
      performed. The extent of tumor regression was histologically evaluated and
      therapy-induced alterations were graded semiquantitatively. Thereby, a
      significantly favorable prognosis was observed in the group of patients that
      showed a regression of carcinomas of 90% or more. Additionally, the extent of a
      resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates
      correlated with the grade of regression. These results underline the importance
      of an exact examination and histomorphological evaluation of the response for the
      assessment of survival probability after neoadjuvant radiochemotherapy of
      oesophageal carcinomas.

PMID- 15168075
TI  - Intragenic suppressors that restore the activity of the maturase encoded by the
      second intron of the Saccharomyces cerevisiae cyt b gene.
AB  - The protein encoded by the second intron (bi2) of the mitochondrial cyt b gene
      from Saccharomyces cerevisiae functions as a maturase promoting intron splicing.
      This protein belongs to a large family characterized by the presence of two
      conserved motifs: LAGLIDADG (or P1 and P2). We have isolated and characterized
      spontaneous revertants from two mis-sense mutations, G85D and H92P (localized in
      the P1 motif of the bi2-maturase), that have a detrimental effect on intron
      splicing. All analyzed revertants are intragenic and resulted from
      monosubstitutions in the mutated codons. Only true back-mutations that restor the
      initial glycine 85 and a pseudoreversion that replaces the deleterious aspartic
      acid 85 by alanine were found in revertants of the mutant G85D. In contrast, all
      possible monosubstitutions in the mutated codon H92P were identified among the
      revertants of this mutant. The maturase activity of all novel forms of the
      protein is similar to the wild-type protein.

PMID- 15168077
TI  - [Skeletal vascular lesions in childhood and adolescence].
AB  - Currently, vascular lesions are being classified either as tumors with inherent
      proliferative potential or as vascular malformations with early manifestation and
      growth commensurate with the growth of the child. This new classification is also
      applicable to skeletal vascular lesions. 30% of all skeletal vascular lesions
      manifest in the first two decades of life, with a preponderance of malformations.
      They are attributed to disturbances in the complex cascade of angiogenesis and a
      minority may be hereditary. Multiple cutaneous vascular malformations are
      associated with mutations of the TIE2- and Glomulin-Genes. Vascular malformations
      with involvement of multiple skeletal elements may pursue an aggressive course
      and manifest as massive osteolysis. Among the epithelioid vascular tumours of
      bone, also in young patients, benign epithelioid hemangioma can be distinguished
      on a morphological basis from epithelioid hemangioendothelioma as an entity with
      low malignant potential.

PMID- 15168078
TI  - [Pediatric renal cell carcinoma].
AB  - Renal cell carcinoma in children and adolescents is rare and comprises only about
      1% of renal tumors in this age group. Since the last WHO classification in 1997,
      new entities of renal tumors in young patients have been described and have been
      included into the new 2004 WHO renal cell carcinoma classification. Renal cell
      carcinoma associated with neuroblastoma comprises 2.5% of renal cell carcinoma in
      young patients. It occurs several years after neuroblastoma. A large proportion
      of these tumors show allelic imbalance of chromosomes 20q13, 2p31-32.2, 13q22 and
      14q31. TFE3-translocation carcinomas correspond to approximately 20% of renal
      cell carcinomas in the pediatric and adolescent age group. Both translocations
      t(X;17)(p11.2;q25) and t(X;1)(p11.2;q21.2) result in immunohistochemically
      detectable TFE3 protein overexpression. By conventional morphology, TFE3
      translocation carcinomas typically show prominent "voluminous" clear cytoplasm
      and partially papillary architecture. Even according to the revised 2004 WHO
      classification, in children and adolescents, far more renal cell carcinomas than
      in the adult age group are currently not classifiable but constitute a
      phenotypically heterogeneous group with ample potential for future renal cell
      carcinoma subtypes.

PMID- 15168079
TI  - [Proliferation and hTERT expression in neuroblastoma].
AB  - BACKGROUND: Transcription of the catalytic subunit of telomerase, human
      Telomerase Reverse Transcriptase (hTERT), and increased tumor cell proliferation
      are powerful prognostic factors in neuroblastoma. We therefore investigated their
      relationship in a large group of neuroblastomas. METHODS: RT-PCR analysis was
      used to discriminate between the various hTERT transcripts. Tumor cell
      proliferation was assessed immunohistochemically using two different cell-cycle
      specific antibodies and the results were compared by statistical analysis.
      RESULTS AND CONCLUSIONS: 54 out of 115 neuroblastomas showed hTERT transcripts,
      25 of which also possessed full-length transcripts. Full-length hTERT transcripts
      were correlated with MYCN-amplification, with a Ki67-proliferation index > or =
      25% and a repp86-proliferation index > or = 10% (p<0,0001), but only a Ki67
      proliferation index > or = 25% was associated with general hTERT transcription
      (p=0,001). Our data confirm the close relationship between hTERT transcription
      and tumor cell proliferation and further strengthen the exceptional prognostic
      power of the repp86-proliferation index.

PMID- 15168080
TI  - Receptor occupancy theory-based analysis of antiemetic effects and standard doses
      of 5-HT3 receptor antagonists in cancer patients.
AB  - PURPOSE: The aim of this study was to determine the usefulness of receptor
      occupancy theory-based analysis using pharmacokinetic and pharmacodynamic
      parameters for predicting the average receptor occupancy (PhiB) in humans of each
      of five 5-HT3 antagonists administered at standard doses. METHODS: The
      relationship between the PhiB value and the complete vomiting inhibition rate
      after a single intravenous administration of cisplatin (not less than 50 mg/m2)
      was analyzed. RESULTS: The predicted PhiB values after intravenous administration
      and oral administration of 5-HT3 antagonists were more than 65% and 50%,
      respectively, suggesting that relatively high receptor occupancy is required to
      elicit sufficient antiemetic effects of 5-HT3 antagonists. Moreover, significant
      ( P<0.05) linear relationships were found between PhiB values and complete
      vomiting inhibition rates of 5-HT3 antagonists in preventive cisplatin therapy,
      with correlation coefficients higher than 0.9, suggesting that the 5-HT3 receptor
      occupancy is an appropriate index of clinical efficacy of 5-HT3 antagonists, with
      higher receptor occupancy indicating more extensive antiemetic action.
      CONCLUSION: The receptor occupancy theory-based analysis of the antiemetic effect
      of a 5-HT3 receptor antagonist used in this study should be very useful for not
      only estimating a rational dosage regimen but also determining the standard dose
      of a new drug using experimental data obtained in a preclinical study.

PMID- 15168081
TI  - An improved assay for enumeration of circulating endothelial cells.
AB  - Circulating endothelial cells have been established as markers of vascular
      disease, such as small vessel vasculitis, acute vascular rejection in renal
      transplant recipients, and cyclosporine-induced endothelial damage. Enumeration
      of these cells by immunomagnetic isolation and acridine staining remains the gold
      standard but necessitates considerable experience and expenditure. A simpler test
      would therefore be of great utility. Hence, our aim was to develop an improved
      simple assay to enumerate endothelial cells in peripheral blood. We had already
      used various surface markers to corroborate the endothelial origin of cells.
      Here, we studied the enumeration of cell numbers with immunomagnetic isolation
      and a variety of subsequent stains, such as CD31, von Willebrand's factor (vWF)
      immunocytochemistry, and Ulex europaeus lectin-1 (UEA-1). Eventually, we devised
      a simple protocol for enumeration using immunomagnetic isolation and a subsequent
      UEA-1 lectin stain. We evaluated the use of this protocol in parallel to
      immunomagnetic isolation and acridine counting alone in 92 renal transplant
      recipients who underwent renal biopsy. Recovery of various concentrations of
      human umbilical vein endothelial cells from blood was also studied.
      Immunomagnetic isolation and subsequent UEA-1 staining permits easier enumeration
      of circulating endothelial cells in peripheral blood. The assay is simple and
      easy to use, thus allowing for a more widespread use of circulating endothelial
      cells as a marker of vascular damage.

PMID- 15168082
TI  - Massive tears of the rotator cuff treated with a deltoid flap.
AB  - We retrospectively reviewed the charts of 29 patients younger than 65 years at
      surgery treated with deltoid flap reconstruction for massive postero-superior
      rotator cuff tears. All tears involved supraspinatus and infraspinatus tendons
      and were associated with tendon stump retraction to the glenoid rim, a
      preservable long biceps tendon, and an intact subscapularis tendon. Mean follow
      up was 10.5 years. Patient satisfaction rate was 89%. Mean global Constant score
      improved from 43 to 71.5 points, mean pain score from 6.3 to 13.2, mean anterior
      flexion from 100 to 157 degrees, and force in elevation from 2.3 to 3 kg. Two
      thirds of patients had no humeral head migration. Of the 18 patients whose flap
      was examined by magnetic resonance imaging, 15 had no tear and 12 had a flap
      signal of muscle intensity; mean flap thickness was 5 mm. Pre-operative factors
      associated with poorer outcomes were upwards humeral head migration with a
      subacromial space smaller than 6 mm, presence of glenohumeral osteoarthritis, and
      supraspinatus amyotrophy greater than 40%. Deltoid flap reconstruction is a valid
      option in this patient population.

PMID- 15168083
TI  - Comparative study of autograft or allograft in primary anterior cruciate ligament
      reconstruction.
AB  - Between December 1996 and December 2002, we treated 79 patients with arthroscopy
      assisted anterior cruciate ligament (ACL) reconstructions. In 53 patients we used
      autografts and in 26 patients allografts. Patients were followed up for 38 (12
      72) months. The two groups did not differ in preoperative sport activity level.
      The postoperative Lysholm score was 89.9+/-8.1 in the autograft group and 84.1+/
      18.6 in the allograft group. Comparing the patients' Lysholm score according to
      whether they had a low (1-5) or a high (6-10) postoperative Tegner score, we
      found no statistically significant difference between the groups. On one
      occasion, the allograft ruptured during the implantation procedure just prior to
      the fixation. Postoperatively, we performed three revisions-two in the allograft
      group and one in the autograft group-and three second-look arthroscopies. There
      were no bacterial infections and no cases of viral transmission. No immune
      rejection, resorption, or immunsynovitis occurred during the follow-up.

PMID- 15168084
TI  - Mini-incision posterior approach for total hip arthroplasty.
AB  - We compared the short-term outcomes of 50 total hip arthroplasties performed
      through a mini-incision posterior approach with those of 42 arthroplasties
      performed through a conventional posterior approach. There were no significant
      differences in age, gender, and bodymass index between groups. The mean operative
      time was shorter (99+/-26 versus 123+/-30 min), and the peroperative mean blood
      loss was smaller with the mini-incision (339+/-210 versus 422+/-177 ml). There
      was no significant difference between groups in post-operative mean blood loss,
      mean inclination angle of acetabular components, percentage of hips with good
      inclination angle, and mean hip score at 6 months after surgery. There was one
      infection in the conventional group but none in the mini group. There were no
      dislocations or symptomatic pulmonary embolism in either group. With the mini
      incision posterior approach, surgical invasion was reduced, and short-term
      outcome was as good as with a conventional posterior approach.

PMID- 15168085
TI  - The management of extra-abdominal desmoid tumours.
AB  - We performed a retrospective analysis of 35 cases of desmoid tumours (aggressive
      fibromatoses) that underwent treatment at our institutions between 1987 and 2002.
      The purpose was to evaluate the rate of local recurrence of desmoid tumours
      treated with surgical excision, to assess the impact of surgical margins on local
      recurrence and to define the role of radiotherapy in the treatment. Nine patients
      experienced a recurrence at an average of 16 months after initial treatment.
      Seven of the 15 patients with a less-than-wide margin had a local recurrence.
      Comparatively, only two of the 20 patients with a wide margin had a local
      recurrence. Thirty-three of the 35 patients were disease free at the last follow
      up. We recommend wide excision with clear margins whenever possible. Marginal
      resections are appropriate when wide excision would severely compromise the
      function of the limb. Surgical resections and selective supplementation of
      adjuvant radiotherapy give excellent control rates.

PMID- 15168086
TI  - Targeting of tumor cells by lymphocytes engineered to express chimeric receptor
      genes.
AB  - Adoptive cellular immunotherapy of cancer has been limited to date mostly due to
      the poor immunogenicity of tumor cells, the immunocompromised status of cancer
      patients in advanced stages of their disease, and difficulties in raising
      sufficient numbers of autologous tumor-specific T lymphocytes. On the other hand,
      the slow tumor penetration and short half-life of exogenously administered tumor
      specific monoclonal antibodies have provided major obstacles for an effective
      destruction of tumor cells by the humoral effector arm of the immune system.
      Attempts to improve the efficacy of adoptive cellular cancer immunotherapy have
      led to the development of novel strategies that combine advantages of T cell
      based (i.e., efficient tumor penetration, cytokine release and cytotoxicity) and
      antibody-based (high specificity for tumor-associated antigens) immunotherapy by
      grafting cytotoxic T lymphocytes (CTLs) with chimeric receptors composed of
      antibody fragments (which recognize tumor-cell antigens) and a cellular
      activation motif. Antigen recognition is therefore not restricted by major
      histocompatibility genes, as the physiological T-cell receptor, but rather is
      directed to native cell surface structures. Since the requirements of major
      histocompatibility complex (MHC) restriction in the interaction of effector cells
      with target cells are bypassed, the tumor cell-binding of CTLs grafted with
      chimeric receptors is not affected by down-regulation of HLA class I antigens and
      by defects in the antigen-processing machinery. Ligand binding by the chimeric
      receptor triggers phosphorylation of immunoglobulin tyrosine activation motifs
      (ITAMs) in the cytoplasmic region of the molecule and this activates a signaling
      cascade that is required for the induction of cytotoxicity, cytokine secretion
      and proliferation. Here, the authors discuss the potential of lymphocytes grafted
      with chimeric antigen receptors in the immunotherapy of malignant disease.

PMID- 15168087
TI  - CRM197 (nontoxic diphtheria toxin): effects on advanced cancer patients.
AB  - PURPOSE: Many years ago, diphtheria toxin (DT) showed antitumor activity in mice
      and in humans, but it was unclear whether this depended on the toxicity of the
      molecule only or on its strong inflammatory-immunological property as well. To
      deal with this open question, we planned to treat a group of cancer patients with
      cross-reacting material 197 (CRM197). CRM197 is a nontoxic mutant of DT that
      shares the immunological properties of the native molecule and its ability to
      bind to heparin-binding epidermal growth factor (HB-EGF), the specific cell
      membrane receptor for DT that is often overexpressed in cancer. METHODS: 25
      outpatients with various advanced tumors who were refractory to standard
      therapies (23 subjects) or had refused, in whole or in part, conventional
      therapies (2 subjects) were treated with CRM197 injected subcutaneously in the
      abdominal wall, on alternate days, for 6 days. Three different dosages (1.7, 2.6,
      or 3.5 mg/day) were used according to the patient's degree of immunological
      reactivity to DT/CRM197 (none, moderate, or high). RESULTS: After the first
      administration of CRM197, a significant increase in the number of circulating
      neutrophils and in the serum level of TNF-alpha was detected. Toxicities were
      minimal. Only patients with delayed-type hypersensitivity to DT/CRM197 had
      irritating skin reactions in the injection sites and a flu-like syndrome with
      fever. Pharmacokinetics showed a mean peak concentration (12.7 ng/ml) 12 h after
      the first injection and a mean half-life of 18.1 h. There were two complete and
      one partial responses (metastatic breast carcinoma, neuroblastoma, and metastatic
      breast carcinoma) lasting 4, 45+, and 15 months, respectively. Six cases of
      stable disease, lasting from 1 to 15 months, were also recorded. CONCLUSIONS:
      CRM197 injected subcutaneously elicited an inflammatory-immunological reaction,
      caused tolerable toxicities, was absorbed to a good extent into the circulatory
      system, and exerted some degree of biological antitumor activity. A possible role
      of neutrophils and TNF-alpha in the mode of action of the molecule is
      hypothesized.

PMID- 15168088
TI  - A catheter-based radiation detector for endovascular detection of atheromatous
      plaques.
AB  - PURPOSE: Although various radiopharmaceuticals have been developed for the
      detection of atheromas, external imaging techniques have limitations when it
      comes to the detection of small plaques. In this study, we developed a charged
      particle-sensitive detector for the endovascular detection of small plaques.
      METHODS: The device consists of a probe, an automatic pullback unit and a
      controller. The probe, which consists of a plastic scintillator and flexible
      optical fibres, is 1.0 mm in diameter. The probe was inserted into a catheter
      placed on (18)F point sources, and then the radioactivity was measured as the
      probe was pulled out stepwise. RESULTS: The sensitivity for (18)F was 9.3
      cps/kBq, and there was a close linear correlation between the peak counts and
      source dose until at least 0.8 MBq. Furthermore, this device showed low
      background counts (<0.1 cps) and a low detection limit (0.21 kBq). To investigate
      the effect of background radioactivity on the measurement at the point sources, a
      ball phantom was prepared and five (18)F point sources were set on the ball's
      surface. Even though 298 MBq of (18)F-fluorodeoxyglucose was injected into the
      ball, the point sources located every 10 mm on the ball's surface were detectable
      separately. CONCLUSION: The data gathered suggest that a catheter-based radiation
      detector in combination with charged particle-emitting radiopharmaceuticals is
      useful for the endovascular detection of small lesions such as coronary plaques.

PMID- 15168090
TI  - Is BMIPP a sensitive marker for myocardial ischaemic stress? Against.

PMID- 15168089
TI  - Is BMIPP a sensitive marker for myocardial ischaemic stress? For.

PMID- 15168091
TI  - Influence of culture passages on growth kinetics and adenovirus vector production
      for gene therapy in monolayer and suspension cultures of HEK 293 cells.
AB  - To characterize the changes in cell growth rate and adenovirus vector (AdV)
      production capability of 293 cells during culture passages, 293 cells obtained at
      the 31st culture passage from ATCC (293M #31) were maintained as a monolayer
      culture and 293 cells obtained at an unknown culture passage from Invitrogen
      (293S) were maintained as suspension culture. In monolayer culture, the specific
      growth rate (micro) of 293M cells increased rapidly with culture passage up to
      passage 65 and thereafter became saturated. The micro of 293M passage 43 (#43)
      was 0.29 day(-1), while the average micro of 293M from #66 to #86 was 0.74+/-0.01
      day(-1) (average +/- standard deviation). It was also noted that the cells became
      smaller in size during early culture passages. AdV production was also influenced
      by the number of culture passages. The AdV titer in the culture of 293M #66 was
      ca. tenfold higher than that of 293M #44, resulting from both a higher cell
      concentration and a higher AdV titer per cell at #66. In contrast, the micro,
      cell size, and AdV production of 293S cells in suspension culture did not change
      significantly as the culture passage number increased up to #40. Taken together,
      the culture passage influenced cell growth and AdV production of 293M cells in
      monolayer culture, but not those of 293S cells in suspension culture.

PMID- 15168093
TI  - Streptomyces lividans and Brevibacterium lactofermentum as heterologous hosts for
      the production of X22 xylanase from Aspergillus nidulans.
AB  - The Aspergillus nidulans gene xlnA coding for the fungal xylanase X22 has been
      cloned and expressed in two heterologous bacterial hosts: Streptomyces lividans
      and Brevibacterium lactofermentum. Streptomyces strains yielded 10 units/ml of
      xylanase when the protein was produced with its own signal peptide, and 19
      units/ml when its signal peptide was replaced by the one for xylanase Xys1 from
      Streptomyces halstedii. B. lactofermentum was also able to produce xylanase X22,
      affording 6 units/ml upon using either the Aspergillus xlnA signal peptide or
      Streptomyces xysA. These production values are higher than those previously
      reported for the heterologous expression of the A. nidulans xlnA gene in
      Saccharomyces cerevisiae (1 unit/ml). Moreover, the X22 enzyme produced by
      Streptomyces lividans showed oenological properties, indicating that this
      Streptomyces recombinant strain is a good candidate for the production of this
      enzyme at the industrial scale.

PMID- 15168092
TI  - Investigation of factors influencing production of the monocyclic carotenoid
      torulene in metabolically engineered Escherichia coli.
AB  - Factors influencing production of the monocyclic carotenoid torulene in
      recombinant Escherichia coli were investigated by modulating enzyme expression
      level, culture conditions, and engineering of the isoprenoid precursor pathway.
      The gene dosage of in vitro evolved lycopene cyclase crtY2 significantly changed
      the carotenoid profile. A culture temperature of 28 degrees C showed better
      production of torulene than 37 degrees C while initial culture pH had no
      significant effect on torulene production. Glucose-containing LB, 2xYT, TB and MR
      media significantly repressed the production of torulene, and the other
      carotenoids lycopene, tetradehydrolycopene, and beta-carotene, in E. coli. In
      contrast, glycerol-containing LB, 2xYT, TB, and MR media enhanced torulene
      production. Overexpression of dxs, dxr, idi and/or ispA, individually and
      combinatorially, enhanced torulene production up to 3.1-3.3 fold. High torulene
      production was observed in a high dissolved oxygen level bioreactor in TB and MR
      media containing glycerol. Lycopene was efficiently converted into torulene
      during aerobic cultures, indicating that the engineered torulene synthesis
      pathway is well coordinated, and maintains the functionality and integrity of the
      carotenogenic enzyme complex.

PMID- 15168094
TI  - Cloning of glyceraldehyde-3-phosphate dehydrogenase gene and use of the gpd
      promoter for transformation in Flammulina velutipes.
AB  - The glyceraldehyde-3-phosphate dehydrogenase gene of Flammulina velutipes was
      isolated. The complete gpd sequence (from ATG to TAA) was 1,489 bp in length and
      contained nine introns. The locations of these nine introns were similar to those
      of other basidiomycetes, which might reflect the evolutionary divergence of these
      mushrooms. The F. velutipes gpd gene was found to encode a protein of 339 amino
      acids and its putative amino acid sequence revealed a high similarity to an
      analogous protein deriving from other basidiomycetes. Results of Southern blot
      analysis suggested that there existed only one copy of the gpd gene in the genome
      of F. velutipes and that there was one typical TATA box and two CAAT boxes
      located in the 5' flanking region. The F. velutipes gpd promoter was fused to a
      hygromycin B phosphotransferase gene (hph) derived from Escherichia coli as a
      selection marker. Using the resulting construction, hph was efficiently
      transformed into F. velutipes by basidiospore electroporation. No false-positive
      antibiotic-resistant cultures were detected by PCR amplification and the
      hygromycin resistance trait was maintained stably during mitotic cell division
      for 3 months. Southern analysis of transformants indicated the integration of
      gene might occur by non-homologous recombination. This rapid and convenient
      electroporation procedure offers new prospects for the genetic manipulation and a
      tool for tagging genes of this important edible mushroom species. Sequence data
      will appear in the DDBJ/EMBL/GenBank nucleotide sequence database under accession
      number AF515622.

PMID- 15168096
TI  - Expression of Sulfolobus solfataricus alpha-glucosidase in Lactococcus lactis.
AB  - The industrial potential to use extreme thermophilic microorganisms and their
      enzymes lies in applications in which the temperature cannot be adjusted (cooled)
      at will. The production of enzymes from wild-type thermophiles is very low,
      therefore, for industrial applications, it is necessary to use recombinant
      microorganisms. In this paper, the cloning of a heat-stable alpha-glucosidase
      from Sulfolobus solfataricus using lactic acid bacteria as expression system is
      reported. The extremophilic alpha-glucosidase was cloned in Lactococcus lactis
      and correctly folded despite being expressed at a lower temperature. The
      recombinant cells were assayed for enzyme residual activity at 75 degrees C in
      order to analyze the direct use of whole cells as biocatalysts. Maximum activity
      corresponded to 40 U/l in static cultures. The protein yield was further improved
      by optimizing fermentation and reached 600 U/l in batch mode. Microfiltration led
      to an even higher enzyme production of 850 U/l as a result of increased biomass.
      The overall production of alpha-glucosidase using the engineered L. lactis strain
      in microfiltration fermentation is 1,000-fold higher than obtained using the wild
      type.

PMID- 15168095
TI  - Enzymatic conversion of D-galactose to D-tagatose: heterologous expression and
      characterisation of a thermostable L-arabinose isomerase from Thermoanaerobacter
      mathranii.
AB  - The ability to convert D-galactose into D-tagatose was compared among a number of
      bacterial L-arabinose isomerases ( araA). One of the most efficient enzymes, from
      the anaerobic thermophilic bacterium Thermoanaerobacter mathranii, was produced
      heterologously in Escherichia coli and characterised. Amino acid sequence
      comparisons indicated that this enzyme is only distantly related to the group of
      previously known araA sequences in which the sequence similarity is evident. The
      substrate specificity and the Michaelis-Menten constants of the enzyme determined
      with L-arabinose, D-galactose and D-fucose also indicated that this enzyme is an
      unusual, versatile L-arabinose isomerase which is able to isomerise structurally
      related sugars. The enzyme was immobilised and used for production of D-tagatose
      at 65 degrees C. Starting from a 30% solution of D-galactose, the yield of D
      tagatose was 42% and no sugars other than D-tagatose and D-galactose were
      detected. Direct conversion of lactose to D-tagatose in a single reactor was
      demonstrated using a thermostable beta-galactosidase together with the
      thermostable L-arabinose isomerase. The two enzymes were also successfully
      combined with a commercially available glucose isomerase for conversion of
      lactose into a sweetening mixture comprising lactose, glucose, galactose,
      fructose and tagatose.

PMID- 15168097
TI  - Congenital bilateral perisylvian syndrome with pituitary hypoplasia and ectopic
      neurohypophysis.
AB  - Congenital bilateral perisylvian syndrome (CBPS) is a congenital neurological
      syndrome characterized by pseudobulbar palsy, cognitive deficits and bilateral
      perisylvian abnormalities observed on imaging. The described abnormality in CBPS
      is polymicrogyria located in the frontal, parietal, and/or occipital lobes. A few
      syndromes or abnormalities associated with this syndrome have been documented.
      Pituitary abnormalities are rare disorders. Association of CBPS with pituitary
      abnormalities has not been reported previously. In this case, a combination of
      bilateral perisylvian polymicrogyria with pituitary hypoplasia and ectopic
      neurohypophysis, caused by a possible single common insult, is presented.

PMID- 15168098
TI  - Endovascular recanalization of acute atherothrombotic carotid artery occlusion
      holds up progressive stroke.
AB  - In acute carotid artery occlusion, hemodynamic compromise in addition to artery
      artery thromboembolism is the mechanism of ischemia that may lead to a
      progressive clinical course with enlarging infarcts. The natural course of
      carotid artery occlusion with a progressive stroke is unfavorable with only about
      10% of patients making a good recovery. We report on two patients in whom
      emergency recanalization of acute carotid artery occlusion with self-expanding
      stents restored cerebral blood flow and held up progressive stroke.

PMID- 15168099
TI  - Effects of desloratadine, diphenhydramine, and placebo on driving performance and
      psychomotor performance measurements.
AB  - INTRODUCTION: First-generation antihistamines taken for relief of allergic
      rhinitis are sedating and pose potential risks for those driving a car or
      operating machinery. Desloratadine is a potent, selective, histamine H(1)
      receptor antagonist that does not easily cross the blood-brain barrier. It is
      nonsedating at therapeutic doses and should not affect driving or psychomotor
      performance. OBJECTIVE: This study compared the acute effects of desloratadine
      with diphenhydramine (active control) and placebo on the performance of healthy
      subjects evaluated with standard over-the-road driving tests (primary objective).
      The subjects' performances were also evaluated (secondary objective) with the use
      of conventional performance tests. METHODS: Eighteen men and women received a
      single dose of desloratadine 5 mg, diphenhydramine 50 mg, or placebo during each
      period of this randomized, double-blind, three-way, crossover study. Two hours
      post-dosing, subjects operated a specially instrumented vehicle in a 90-min test
      designed to measure their ability (1) to maintain constant speed and lateral
      position while following another vehicle at a constant distance and (2) to
      respond to brake signals. Additionally, a full battery of performance tests was
      administered. RESULTS: No significant differences were noted between
      desloratadine and placebo in standard deviation of lateral position (SDLP),
      whereas diphenhydramine treatment significantly increased SDLP ( P< 0.001 for
      both comparisons). Brake reaction time was significantly faster following
      treatment with desloratadine than diphenhydramine (473.72 ms vs 541.22 ms; P<
      0.001) or placebo (512.06 ms; P=0.033). No differences were seen among treatments
      in deviation of speed or distance to the lead car. The majority of performance
      tests showed no significant differences among groups. CONCLUSION: Desloratadine
      at a therapeutic dose does not impair driving performance.

PMID- 15168100
TI  - Increased psychotropic drug consumption by children in the Netherlands during
      1995-2001 is caused by increased use of methylphenidate by boys.
AB  - OBJECTIVE: The aim of the study was to determine the changes in consumption of
      psychotropic drugs by children aged less than 18 years during the years 1995 to
      2001 in the Netherlands. METHODS: The year prevalence of antipsychotics,
      benzodiazepines, antidepressants and psychostimulants for boys and girls under 18
      years was determined using electronic pharmacy dispensing records obtained from
      the PHARMO database. RESULTS: The overall prevalence of psychotropic drugs
      increased from 11.1 per 1000 in 1995 to 22.9 per 1000 in 2001. This increase
      could almost completely be attributed to the increase in the use of
      psychostimulants, i.e. methylphenidate, which increased from 1.7 per 1000
      children in 1995 to 10.0 per 1000 in 2001. For the other psychotropic drugs, no
      or only a small increase was seen. For both boys and girls, the use of
      psychostimulants was highest in the age group of 5-14 years. CONCLUSION: During
      the years 1995-2001, the consumption of psychotropic drugs by children in the
      Netherlands has more than doubled. This increase could largely be attributed to
      an increased use of the psychostimulant methylphenidate by boys of the age 5-14
      years.

PMID- 15168101
TI  - Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma
      concentrations and clinical effects of antidepressants in a naturalistic clinical
      setting.
AB  - OBJECTIVE: This evaluation focuses on polymorphisms of the cytochrome-P450 (CYP)
      isoenzymes 2C9, 2C19 and 2D6 and their association with plasma concentrations
      within a typical clinical setting. Side effects and treatment response were
      analysed in an exploratory approach in poor and ultra-rapid metabolisers.
      PATIENTS AND METHODS: We analysed 136 Caucasian depressed inpatients treated with
      amitriptyline, citalopram, clomipramine, doxepin, fluvoxamine, mirtazapine,
      paroxetine, sertraline and venlafaxine, who underwent weekly plasma concentration
      measurements, assessment of the severity of illness and side effects during their
      stay in the hospital. Patients were genotyped with respect to CYP2C9 alleles *1
      and *2, the CYP2C19 alleles *1, *2 and *3 and the CYP2D6 alleles *1 to *9 and
      CYP2D6 gene duplication. RESULTS: CYP2D6 poor metaboliser genotype and co
      medication with inhibitors of CYP2D6 were associated with higher plasma
      concentrations than the drug-specific median plasma concentration when normalised
      to dose; plasma concentrations of CYP2C19 extensive metabolisers and smokers were
      significantly lower than the drug-specific median. Five of the six CYP2D6 poor
      metabolisers experienced side effects. Response was not associated with plasma
      concentrations above or below the lower limit of a presumed therapeutic range.
      CONCLUSION: These data indicate a significant influence of the CYP2D6 genotype,
      minor influence of the CYP2C19 genotype and no influence of the CYP2C9 genotype
      on plasma concentrations of patients taking mainly second-generation
      antidepressants. Because of the good tolerability of the latter and the flat dose
      response relationship, genotyping should only be considered in cases of suspected
      side effects.

PMID- 15168102
TI  - Continuous infusion of medications in very low birth weight infants.
AB  - OBJECTIVE: To develop a safe and accurate method for the administration in the
      neonatal intensive care unit of several potent medications as a continuous
      infusion without overloading the infant, especially the very low birth weight
      (VLBW) infant by diluents. METHOD: The method designed is based on a weight
      adapted solution limiting the diluent administration and allowing for a versatile
      modulation of dose administration. As this method was initially designed for VLBW
      infants, the point of departure of this method is a standard maximal fluid load
      of 0.3 ml/h for each medication, delivered in a low compliant circuit with a high
      precision syringe driver. Solutions are made for 24 h, which is a compromise
      between drug stability and repeated pressure drops in the circuit when changing
      the syringe and administration set. To translate a prescription into a solution a
      conversion factor is calculated. In addition to the calculation principle, this
      conversion factor is given for a number of commonly used drugs in neonatal care.
      CONCLUSIONS: In our experience, the method described adds to the safety and
      accuracy of continuous drug administration in neonatal care.

PMID- 15168103
TI  - Medication use during pregnancy: data from the Avon Longitudinal Study of Parents
      and Children.
AB  - OBJECTIVE: To present data on the self-reported use of all types of medicinal
      products collected during pregnancy in a large cohort in southwest England.
      METHODS: Pregnant women with a delivery date during 1991-1992 and forming part of
      the prospective, population-based Avon Longitudinal Study of Parents and Children
      (ALSPAC) were sent up to four self-completion postal questionnaires during
      pregnancy. Text data collected from the questions on drug usage were coded using
      an ALSPAC drug dictionary based on the World Health Organization Drug Dictionary.
      RESULTS: At least one antenatal self-completion questionnaire was completed for
      14,119 pregnancies, and 11,545 women completed all four. The data included
      prescription, over-the-counter, herbal and homeopathic products as well as iron,
      vitamins and other supplements. Only 7.6% did not report use of any medicinal
      product throughout their entire pregnancy. The remaining 92.4% used at least one
      product at some stage. After exclusion of iron, folate, vitamins, supplements,
      herbal and homeopathic products and skin emollients, 83% of those completing all
      questionnaires had used conventional therapeutic drugs. Analgesics were reported
      by approximately one-third of women at each stage during pregnancy, and
      paracetamol was the most frequently reported substance. Iron preparations were
      reported by 33% of the full cohort, at some stage, and folate by 21.9%. Use of
      anti-anaemic products increased during pregnancy with the greatest incidence at
      32 weeks. Other vitamins and supplements were taken by 17.4% at some stage. Use
      of vitamins decreased throughout pregnancy from 9.6% in early pregnancy to 5% at
      32 weeks. Antacids were reported by 23% at 32 weeks. The reported incidence of
      antibiotic use decreased slightly during pregnancy from 8% early on to 5.8% at 32
      weeks; amoxicillin was the most frequently reported antibacterial. CONCLUSION:
      Use of medicinal products was high during pregnancy in the ALSPAC cohort. This
      finding is consistent with data from recent publications.

PMID- 15168104
TI  - Evaluation of patient chemotherapy education in a gynecology oncology center.
AB  - GOALS OF WORK: To assess the level at which patient chemotherapy education needs
      are being met by the health-care team in an outpatient clinic setting and to
      identify any unmet needs regarding patient chemotherapy education. PATIENTS AND
      METHODS: A questionnaire comprising 17 questions was developed to evaluate
      patient preferences regarding chemotherapy education. In the clinic, patients
      were offered a copy of the questionnaire with a cover letter describing the
      study. MAIN RESULTS: A total of 282 questionnaires were completed, and 190
      respondents had previously received chemotherapy. Of the 165 respondents who were
      previously treated at our institution, 66.7% (110) had received some form of
      chemotherapy education specifically from our clinic. The majority of all
      respondents (86.8%) reported that they preferred to receive information about
      their chemotherapy via written materials and/or through a conversation with a
      health-care professional. Regardless of the source of information, 62.6% of
      respondents (119) felt they were provided with adequate information about their
      chemotherapy treatment, and 42.4% reported that they would like more information
      about their chemotherapy. CONCLUSIONS: The current practice in our clinic is to
      provide patients with written information about their chemotherapy that is
      reviewed with a health-care professional. The data revealed that our current
      practice is consistent with our patients' preferences. However, this survey did
      identify new information that patients want to know about chemotherapy, such as
      how chemotherapy works, why chemotherapy stops working, and drug-drug as well as
      drug-food interactions. This information will be incorporated into future patient
      education materials.

PMID- 15168106
TI  - A giant novel gene undergoing extensive alternative splicing is severed by a
      Cornelia de Lange-associated translocation breakpoint at 3q26.3.
AB  - Cornelia de Lange syndrome (CdLS) is a rare developmental malformation syndrome
      characterised by mental handicap, growth retardation, distinctive facial features
      and limb reduction defects. The vast majority of CdLS cases are sporadic. We
      carried out a high density bacterial artificial chromosome (BAC) microarray
      comparative genome hybridisation screen but no evidence was found for a
      consistent pattern of microdeletion/microduplication. As an alternative, we
      focused on identifying chromosomal regions spanning associated translocation
      breakpoints. We prioritised the distal 3q region because of the occurrence, in a
      classical CdLS patient, of a de novo balanced translocation with a breakpoint at
      3q26.3 and of reports of phenotypic overlap between cases of mild CdLS and
      individuals trisomic for the 3q26-q27 region. We show that the 3q26.3 breakpoint
      severs a previously uncharacterised giant gene, NAALADL2, containing at least 32
      exons spanning 1.37 Mb. Northern blot analysis identified up to six different
      transcripts in the 1-10 kb range with strongest expression in kidney and
      placenta; embryonic expression was largely confined to duodenal and stomach
      endoderm, mesonephros, metanephros and pancreas. Transcript analysis identified
      extensive alternative splicing leading to multiple 5' and 3' untranslated regions
      and variable coding sequences. Multiple protein isoforms were defined by
      different N-terminal regions (with at least four alternative initiating
      methionine codons), and by differential protein truncation/use of alternative C
      terminal sequences attributable to alternative splicing/polyadenylation. Outside
      the N-terminal regions, the predicted proteins showed significant homology to N
      acetylated alpha-linked acidic dipeptidase and transferrin receptors. Mutation
      screening of NAALADL2 in a panel of CdLS patient DNA samples failed to identify
      patient-specific mutations. We discuss the possibility that the 3q26.3
      translocation could nevertheless contribute to pathogenesis.

PMID- 15168105
TI  - Do floral syndromes predict specialization in plant pollination systems? An
      experimental test in an "ornithophilous" African Protea.
AB  - We investigated whether the "ornithophilous" floral syndrome exhibited in an
      African sugarbush, Protea roupelliae (Proteaceae), reflects ecological
      specialization for bird-pollination. A breeding system experiment established
      that the species is self-compatible, but dependent on visits by pollinators for
      seed set. The cup-shaped inflorescences were visited by a wide range of insect
      and bird species; however inflorescences from which birds, but not insects, were
      excluded by wire cages set few seeds relative to open-pollinated controls. One
      species, the malachite sunbird (Nectarinia famosa), accounted for more than 80%
      of all birds captured in P. roupelliae stands and carried the largest protea
      pollen loads. A single visit by this sunbird species was enough to increase seed
      set considerably over unvisited, bagged inflorescences. Our results show that P.
      roupelliae is largely dependent on birds for pollination, and thus confirm the
      utility of floral syndromes for generating hypotheses about the ecology of
      pollination systems.

PMID- 15168107
TI  - Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in
      patients with primary breast cancer: a pilot study.
AB  - PURPOSE: Combining anthracyclines and taxanes are to date the most active
      cytotoxic treatment option in the neoadjuvant and palliative therapy of breast
      cancer patients. Adding trastuzumab to these cytotoxic agents can improve outcome
      for women with human epidermal growth factor receptor 2 (HER2)-overexpressing
      advanced breast cancer. We conducted a pilot study of preoperative epidoxorubicin
      and docetaxel plus trastuzumab in outpatient patients suffering from breast
      cancer. PATIENTS AND METHODS: Fourteen consecutive patients were enrolled in this
      prospective clinical pilot trial. Preoperative treatment consisted of weekly
      trastuzumab (4 mg/kg body-weight loading dose, 2 mg/kg/week maintenance dose), in
      combination with weekly epidoxorubicin (30 mg/m2 body surface area [BSA]) and
      docetaxel (35 mg/m2 BSA) once a week for 6 weeks followed by 1 week off therapy.
      RESULTS: Patients received a total of 30 cycles (median: 2 cycles, range: 2-3
      cycles) of this therapeutic regimen. Outpatient epidoxorubicin and docetaxel plus
      trastuzumab were well tolerated. A major response to this preoperative therapy
      regimen could be demonstrated in 12 of 14 patients (86%) leading to breast
      conserving surgery in 11 of 14 patients (79%). CONCLUSIONS: We conclude that
      outpatient epidoxorubicin and docetaxel plus trastuzumab are safe in the
      neoadjuvant treatment of patients suffering from breast cancer, based on a
      favorable side-effect and activity profile. Thus, this regimen can be considered
      for further clinical trials.

PMID- 15168110
TI  - Gender differences in newborn subcutaneous fat distribution.
AB  - The pattern and distribution of subcutaneous fat in term and preterm newborns has
      been assessed by skinfold thicknesses (ST), describing gender and gestational age
      variations. Weight, length and ST (triceps, biceps, subscapular and suprailiac)
      were measured in 4634 neonates (2445 males and 2189 females) aged from 32 to 41
      gestational weeks. Central to total skinfold ratio (CTS), (suprailiac +
      subscapular)/sum of 4 ST, was calculated. Males were heavier and longer than
      females. The sum of 4 ST and CTS was higher in females at every gestational age
      (with significant differences from 35 weeks) and also the sum of 4 ST per kg body
      weight (P < 0.05 from 32-33 weeks). Throughout the gestational period, ST
      increased significantly (P < 0.0001) but CTS did not show variations, neither in
      males nor in females. CONCLUSION: term and preterm females have a more
      centralised pattern and more amount of subcutaneous fat than males. Central to
      total skinfold ratio must be considered as an index of centripetal fat store
      which is independant of gestational age.

PMID- 15168108
TI  - Wegener granulomatosis in childhood and adolescence.
AB  - Wegener granulomatosis (WG) is a necrotising granulomatous small vessel
      vasculitis with a clinical predilection for involvement of the upper airways,
      lungs and kidneys, which occurs at all ages. The aetiology of WG, like other
      primary systemic vasculitides, remains unknown. Existing evidence suggests an
      autoimmune inflammatory process, characterised by early lesions with neutrophils
      and endothelial cells as active participants and involvement of antineutrophil
      cytoplasmatic antibodies (ANCA) directed against proteinase-3 (PR3). However,
      other concomitant factors like infections and environmental factors also appear
      to be necessary for the development of WG. In addition, multiple genetic factors
      seem to be involved in disease susceptibility. Whereas the first publications on
      WG in childhood were based on case reports, some studies in recent years allow to
      compare clinical findings, disease course, morbidity and mortality rates for
      childhood and adult onset patients. Whereas most aspects of WG are similar at all
      ages, some features appear to be significantly different. WG in childhood is more
      frequently complicated by subglottic stenosis and nasal deformity while treatment
      related morbidity and malignancies are less common compared to adults.
      Introduction of combined treatment with cyclophosphamide and glucocorticoids
      resulted in a dramatic improvement of patient outcome; however, commonly
      occurring disease relapses and the risk of chronic organ damage at all ages make
      long-term follow-up of all patients and the establishment of new therapeutic
      regimens necessary.

PMID- 15168109
TI  - Congenital hypertrophic cardiomyopathy, cataract, mitochondrial myopathy and
      defective oxidative phosphorylation in two siblings with Sengers-like syndrome.
AB  - We describe two siblings with a Sengers-like syndrome, who presented with
      congenital hypertrophic cardiomyopathy, infantile cataract, mitochondrial
      myopathy, lactic acidosis and normal mental development. A mitochondrial adenine
      nucleotide translocator 1 (ANT1) defect was detected since the ANT1 protein was
      not detectable by immmunoblotting in muscle samples of the patients. Additionally
      to these features of classical Sengers syndrome (OMIM 212350), we found that the
      mitochondrial oxidative phosphorylation, measured by biochemical analysis, was
      severely compromised in skeletal muscle in both children. Biochemical and
      morphological analysis of the fibroblasts revealed normal results. The
      association of significantly decreased pyruvate oxidation rates, deficient energy
      production and decreased multiple mitochondrial enzyme-complex activities in the
      muscle samples of our patients is a new finding which differs from previous
      results in patients with Sengers syndrome. CONCLUSION: we recommend a muscle
      biopsy and the biochemical analysis of the oxidative phosphorylation system in
      patients with muscle hypotonia, cardiomyopathy and congenital or infantile
      cataract.

PMID- 15168111
TI  - Diplopia and strabismus convergens mimicking symptoms of tuberculous meningitis
      as side-effects of isoniazid.

PMID- 15168112
TI  - Clinical relevance of anti-phospholipid antibody tests in childhood.

PMID- 15168114
TI  - The hippocampal continuation (indusium griseum): its connectivity in the hedgehog
      tenrec and its status within the hippocampal formation of higher vertebrates.
AB  - The indusium griseum and its precallosal extension are usually considered poorly
      differentiated portions of the hippocampus. The connections of this so-called
      'hippocampal continuation' (HCt) have only been analyzed so far in rodents, which
      show one of the least-developed HCt among mammals. In this study we have
      investigated the relatively well differentiated HCt of the small Madagascan
      hedgehog tenrec (Afrotheria) using histochemical and axonal transport techniques.
      The tenrec's HCt shows associative and commissural connections. It receives
      laminar specific afferents from the entorhinal cortex (collaterals from neurons
      projecting to the dentate area), the anterior and posterior piriform cortices as
      well as the supramammillary region. A few fibers also originate in the olfactory
      bulb and the dentate hilus. Among these input areas only the dentate hilus
      receives a significant reciprocal projection from the HCt. Additional HCt
      efferents are directed to the subcallosal septum (presumed septohippocampal
      nucleus), the olfactory tubercle and the islands of Calleja. With the exception
      of the supramammillary afferents and possible efferents to the supraoptic nucleus
      we failed, however, to demonstrate distinct thalamic and hypothalamic
      connections. A comparison of the connections of the HCt with those of the
      hippocampal subdivisions reveal some similarity between the HCt and the dentate
      area, but the overall pattern of connectivity does not permit a correlation of
      the HCt with the dentate area, let alone the cornu ammonis and the subiculum.
      This view is supported by histochemical findings in the tenrec (immunoreactivity
      to calcium binding proteins) as well as the rat (data taken from the literature).
      The HCt is therefore considered a region in its own right within the hippocampal
      formation. It may be tentatively correlated with the medial cortex of reptiles,
      while the dentate area and the cornu ammonis may have evolved de novo in mammals.

PMID- 15168113
TI  - Pneumococcal pneumonia preceding appendicitis in a child.

PMID- 15168115
TI  - The anatomy of the porcine subthalamic nucleus evaluated with
      immunohistochemistry and design-based stereology.
AB  - This study provides a light-microscopic description of the organization,
      morphology and number of neurons in the subthalamic nucleus (STN) of the
      Gottingen minipig. It is based on histological material stained with Nissl, Golgi
      and autometallographic techniques, and employs design-based stereological
      estimation of the total neuron number. The organization of several
      neurotransmitters in the STN has been evaluated in histological preparations
      stained for acetylcholinesterase (AChE) and immunostained for choline
      acetyltransferase (ChAT), tyrosine hydroxylase (TH), glutamic acid decarboxylase
      (GAD) and glutamate. In all of the stained preparations the STN appeared as a
      distinct lens-shaped structure located in the caudal diencephalon, medial to the
      internal capsule and ventrolateral to the zona incerta. Rostrally, the STN
      approached the globus pallidus pars interna, whereas caudally the ventromedial
      part of the STN was adjacent to the rostral part of the substantia nigra pars
      compacta (SNc), where some of the neurons of the two nuclei merged. The neurons
      in the STN had medium-sized (25-40 microm) ovoid or fusiform cell bodies, from
      which three to six large dendrites emanated in a direction predominantly parallel
      to the long axis of the STN. Immunohistochemistry revealed that most of the
      subthalamic neurons were glutamatergic and differed significantly in appearance
      from the large stellate TH-positive cells of the adjacent SNc. Numerous TH
      positive bouton-rich fibers traversed the STN. The GAD-staining revealed a large
      number of terminals within the boundaries of the STN. The STN was highly AChE
      positive, reflecting a prominent innervation by ChAT-positive terminals. The
      total number of subthalamic neurons in one hemisphere was estimated to be
      approximately 56,000. We conclude that the neuroarchitecture of the porcine STN
      is similar to primates, including humans, and appears well-suited for further
      studies examining the role of the STN in movement disorders.

PMID- 15168116
TI  - Spatial and temporal patterns of apoptosis during differentiation of the retina
      in the turtle.
AB  - We investigated patterns of cell death in the turtle retina that could
      potentially be associated with the innervation of the optic tectum, and looked
      for mechanisms of retinal development that might be common to reptilian and
      homeotherm vertebrates. We used retinas of turtle embryos between the 23rd day of
      incubation (E23) (before the first optic fibres reach the optic tectum) and
      hatching (when all the optic fibres have established synaptic connections). Dying
      retinal neurons were identified in paraffin sections by the TUNEL technique,
      which specifically labels fragmented DNA. Apoptotic cells were found in the
      ganglion cell layer (GCL), the inner nuclear layer (INL), and the outer nuclear
      layer (ONL). Cell death in the GCL was intense between E29 and E47, and had
      disappeared by the day of hatching. In the INL, dead and dying cells were most
      abundant between E31 and E34, and progressively disappeared. The temporal pattern
      in the ONL was similar to the INL although the density was very low. In all the
      nuclear layers cell death spread from the dorso-temporal area of the central
      retina to the periphery. Additional dorsal to ventral and temporal to nasal
      gradients were distinguishable in a quantitative TUNEL analysis. The patterns of
      cell death observed in the developing turtle retina were thus similar to those
      found in birds and mammals. This process could be under the control of
      differentiation gradients in all the vertebrate classes.

PMID- 15168119
TI  - Developmental expression of amphioxus GABAA receptor-associated protein-like 2
      gene.
AB  - A full-length amphioxus gamma-aminobutyric acid type-A receptor-associated
      protein-like 2 ( GABARAPL2) cDNA was isolated. Its sequence and developmental
      expression are first described in this paper. The phylogenetic analysis shows
      that the amphioxus GABARAPL2 and GABARAPL2 in vertebrates are highly homologous.
      The results of in situ hybridization show that the amphioxus GABARAPL2 gene is
      expressed in the neural tube, neurenteric canal, notochord, muscle and developing
      alimentary canal.

PMID- 15168118
TI  - A study into methodology and application of quantification of tumour vasculature
      in rectal cancer.
AB  - The application of new surgical techniques in combination with preoperative
      radiotherapy has minimised the risk of local recurrence in rectal cancer.
      However, distant metastasis is still a serious problem after seemingly curative
      resection in patients with rectal cancer. The present study aimed to evaluate the
      methodology for quantification and the characteristics of the tumour vasculature
      in relation to the development of metastasis in patients with rectal cancer. From
      a large multicentre trial, 88 patients were selected, ensuring a relatively high
      percentage of metastasis. This selection facilitates the study of tumour
      vasculature characteristics in relation to metastasis. Vessel number, perimeter
      and area were assessed at both the invasive front and intratumoural area. Hot
      spot and random selections were performed simultaneously. The median of each
      vessel parameter in the study population was used to separate patients into a low
      and high-vessel group. Differences in development of distant metastasis were
      studied between low- and high-vessel groups. The data of the present study show
      that only vascular perimeter randomly assessed at the invasive front was
      associated with distant metastasis. Patients with a high score had a lower
      distant metastasis rate than patients with a low score (37% and 62%,
      respectively). High-vessel perimeter was independent of tumor node metastasis
      staging, but was associated with an increased presence of immune cells,
      comprising T cells, mast cells, eosinophils and neutrophils. This methodological
      study on the biological relevance of various vessel characteristics showed that a
      large vascular endothelial surface, as reflected by a high perimeter, was the
      only vessel characteristic indicative of improved patient outcome. The underlying
      principle for this association may be the improved immune response.

PMID- 15168117
TI  - Microvessel density, endothelial-cell proliferation and carbonic anhydrase IX
      expression in haematological malignancies, bone-marrow metastases and monoclonal
      gammopathy of undetermined significance.
AB  - The aim of the study was to compare the angiogenic status, potential qualitative
      differences in microvessels and carbonic anhydrase IX expression in bone-marrow
      (BM) metastases and different haematological tumours at time of diagnosis. The
      microvessel density (MVD), endothelial-cell proliferation (ECP) and carbonic
      anhydrase IX (CA IX) immunoreactivity were determined on 210 trephine biopsies
      from 57 patients with multiple myeloma (MM), 13 with acute myeloid leukaemia
      (AML), 48 with chronic myeloproliferative syndrome (CMPS), 26 with chronic
      lymphocytic leukaemia (CLL), 25 with epithelial BM metastases, 18 with monoclonal
      gammopathy of undetermined significance (MGUS) and from a control group composed
      of 23 patients without haematological neoplasm. There was an increased MVD and
      ECP in epithelial BM metastases, MM, AML, CMPS and in a part of CLL. While an ECP
      greater than 0 was detected in 72% of MM, 75% of CMPS and 92% of AML, it was
      invariably observed (100%) in the BM metastases. The absence of ECP together with
      a MVD comparable with the control group in our MGUS cases supports the view that
      MGUS is a pre-angiogenic condition. Qualitative differences in microvessels were
      associated with growth patterns in MM and CLL and were observed between the
      different entities of CMPS. In one-third of the epithelial BM metastases, there
      was a focal CA IX immunoreactivity, which was never observed in the
      haematological diseases.

PMID- 15168120
TI  - Total retrieval time and hypermnesia: investigating the benefits of multiple
      recall tests.
AB  - Hypermnesia is an increase in recall over repeated tests. A core issue is the
      role of repeated testing, per se, versus total retrieval time. Prior research
      implies an equivalence between multiple recall tests and a single test of equal
      total duration, but theoretical analyses indicate otherwise. Three experiments
      investigated this issue using various study materials (unrelated word lists,
      related word lists, and a short story). In the first experimental session, the
      study phase was followed by a series of short recall tests or by a single, long
      test of equal total duration. Two days later, participants took a final recall
      test. The multiple and single test conditions produced equivalent performance in
      the first session, but the multiple test group exhibited less forgetting and
      fewer item losses in the final test. In a fourth experiment, using a brief delay
      (15 min) between the recall sessions, the multiple recall condition produced
      greater hypermnesia as well as fewer item losses. In addition, final recall was
      significantly higher in the multiple than in the single test condition in three
      of the four experiments. Thus, single and repeated recall tests of equal total
      duration are not functionally equivalent, but rather produce differences
      observable in subsequent recall tests.

PMID- 15168121
TI  - Biochemical and immunohistochemical characterization of Mimosa annexin.
AB  - To characterize the biochemical properties of plant annexin, we isolated annexin
      from Mimosa pudica L. and analyzed the biochemical properties conserved between
      Mimosa annexin and animal annexins, e.g. the ability to bind phospholipid and F
      actin in the presence of calcium. We show that Mimosa annexin is distributed in a
      wide variety of tissues. Immunoblot analysis also revealed that the amount of
      annexin is developmentally regulated. To identify novel functions of Mimosa
      annexin, we examined the pattern of distribution and the regulation of its
      expression in the pulvinus. The amount of annexin in the pulvinus increased at
      night and was sensitive to abscisic acid; however, there was no detectable
      induction of annexin by cold or mechanical stimulus. Annexin distribution in the
      cell periphery during the daytime was changed to a cytoplasmic distribution at
      night, indicating that Mimosa annexin may contribute to the nyctinastic movement
      in the pulvinus.

PMID- 15168123
TI  - Strategies that improve human skeletal muscle performance during repetitive, non
      isometric contractions.
AB  - Previous studies have suggested that during sustained maximal voluntary and
      evoked contractions, decreasing activation rates may minimize fatigue. The idea
      of gradually decreasing stimulation frequency to preserve force during fatiguing
      isometric contractions has, however, recently been challenged. The primary
      purpose of this study was to test the effectiveness of decreasing or increasing
      electrical stimulation rates during evoked, repetitive, submaximal, non-isometric
      contractions of healthy human quadriceps femoris muscles. The ability of the
      muscles to produce a 50 degrees knee excursion repetitively was evaluated using
      low-frequency trains, high-frequency trains, and a combination of these trains.
      Results showed that stimulating the muscles with high-frequency trains followed
      by low-frequency trains produced the worst performance and starting with low
      frequency trains followed by high-frequency trains produced the best performance.
      Present results cast doubt on the applicability of decreasing stimulation rates
      during non-isometric contractions and suggest that a combination of trains that
      begin at a low frequency and then switch to a higher-frequency may improve
      performance during functional electrical stimulation.

PMID- 15168124
TI  - Increased postoperative peritoneal adhesion formation after the treatment of
      experimental peritonitis with chlorhexidine.
AB  - BACKGROUND AND AIMS: Chlorhexidine is known as a substance that produces
      adhesions. However, in an experimental model of peritoneal injury, lavage with
      chlorhexidine and saline solutions produced a similar number of adhesions. This
      study was designed to test the hypothesis that chlorhexidine gluconate 0.05%
      solution used for the treatment of peritonitis increases formation of
      postoperative peritoneal adhesions as compared to standard lavage with saline
      solution. MATERIAL AND METHODS: Forty Wistar rats were randomly allocated to
      gastric or faecal peritonitis groups. In each group rats were further randomly
      subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days
      the rats were killed and intraperitoneal adhesions were evaluated by adhesion
      score and grading. RESULTS: Adhesion scores were statistically significantly
      different between saline and chlorhexidine groups in both gastric and faecal
      peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small
      bowel intussusception rate was observed, while there were no such complications
      in the other study groups. The conglomerate of organs formed by dense adhesions
      was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine
      and in only 10% when saline solution was used ( P<0.05). Neither chlorhexidine
      nor saline solutions have caused such dense adhesions in faecal peritonitis.
      CONCLUSION: Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the
      treatment of experimental peritonitis results in increased adhesion formation.

PMID- 15168126
TI  - Breathing thermal manikins for indoor environment assessment: important
      characteristics and requirements.
AB  - Recently, breathing thermal manikins have been developed and used for indoor
      environment measurement, evaluation and optimization as well as validation of the
      computational fluid dynamic predictions of airflow around a human body. Advances
      in the assessment of occupants' thermal comfort and perceived air quality by
      means of breathing thermal manikins have also been made. In order to perform
      accurate measurements and realistic evaluation and assessment, the design and
      characteristics of a manikin must comply with certain requirements. The most
      important of these, such as the number, size and shape of body segments, control
      mode, breathing simulation etc., are discussed and specified in this paper.

PMID- 15168125
TI  - Cancer cachexia.
AB  - CAUSATIVE FACTORS: Nutritional supplementation or pharmacological manipulation of
      appetite are unable to control the muscle atrophy seen in cancer cachexia. This
      suggests that tumour and/or host factors might be responsible for the depression
      in protein synthesis and the increase in protein degradation. An increased
      expression of the ubiquitin-proteasome proteolytic pathway is responsible for the
      increased degradation of myofibrillar proteins in skeletal muscle, and this may
      be due to tumour factors, such as proteolysis-inducing factor (PIF), or host
      factors such as tumour necrosis factor-alpha (TNF-alpha). In humans loss of
      adipose tissue is due to an increase in lipolysis rather than a decrease in
      synthesis, and this may be due to tumour factors such as lipid-mobilising factor
      (LMF) or TNF-alpha, both of which can increase cyclic AMP in adipocytes, leading
      to activation of hormone-sensitive lipase (HSL). Levels of mRNA for HSL are
      elevated twofold in adipose tissue of cancer patients, while there are no changes
      in lipoprotein lipase (LPL), involved in extraction of fatty acids from plasma
      lipoproteins for storage. TREATMENT FOR CACHEXIA: This has concentrated on
      increasing food intake, although that alone is unable to reverse the metabolic
      changes. Agents interfering with TNF-alpha have not been very successful to date,
      although more research is required in that area. The only agent tested clinically
      that is able to interfere with the action of PIF is eicosapentaenoic acid (EPA).
      EPA attenuates protein degradation in skeletal muscle by preventing the increased
      expression of the ubiquitin-proteasome pathway, but has no effect on protein
      synthesis. When used alone EPA prevents further wasting in cachectic patients,
      and, when it is combined with an energy- and protein-dense nutritional
      supplement, weight gain is seen, which is totally lean body mass. These results
      suggest that mechanistic studies into the causes of cancer cachexia will allow
      appropriate therapeutic intervention.

PMID- 15168127
TI  - Mechanomyographic responses in human biceps brachii and soleus during sustained
      isometric contraction.
AB  - The purpose of this study was to elucidate the responses of the mechanomyogram
      (MMG) from two apparently different muscles (biceps brachii and soleus) during a
      sustained voluntary contraction at 50% maximum voluntary contraction. The MMG and
      surface electromyogram (EMG) were recorded from human biceps brachii and soleus
      during sustained elbow flexion and plantar flexion, respectively. Results
      indicated that the slope coefficient of rise in EMG amplitude as a function of
      time for the biceps was significantly greater than that for the soleus (
      P<0.001). On the contrary, the MMG amplitude of the biceps showed a significant
      increase during the initial phase of sustained contraction ( P<0.05); however,
      when exhaustion was approached the amplitude declined significantly ( P<0.05). In
      the soleus muscle the decrease in MMG amplitude toward exhaustion occurred to a
      much lesser extent than that observed in the biceps. This difference could be
      attributed to the nature of the fusion state of the underlying muscle fibers.
      That is, the great extent of fusion observed in the biceps may be as a result of
      a greater quantity of fatigable motor units. In addition, the absence of MMG
      reduction in the soleus would indicate the absence of fatigue-induced slowing of
      contractile machinery and/or the lack of full activation (tetanus) of muscle
      fibers even at the exhaustion phase of plantar flexion.

PMID- 15168128
TI  - Muscle buffer capacity and aerobic fitness are associated with repeated-sprint
      ability in women.
AB  - In addition to a high aerobic fitness, the ability to buffer hydrogen ions (H+)
      may also be important for repeated-sprint ability (RSA). We therefore
      investigated the relationship between muscle buffer capacity (betamin vivo and
      betamin vitro) and RSA. Thirty-four untrained females [mean (SD): age 19 (1)
      years, maximum oxygen uptake (VO2peak) 42.3 (7.1) ml x kg(-1) x min(-1)]
      completed a graded exercise test (GXT), followed by a RSA cycle test (five 6-s
      sprints, every 30 s). Capillary blood was sampled during the GXT and before and
      after the RSA test to determine blood pH (pHb) and lactate concentration ([La
      ]b). Muscle biopsies were taken before (n=34) and after (n=23) the RSA test to
      determine muscle lactate concentration ([La-]i), hydrogen ion concentration
      ([H+]i) pHi, betamin vivo and betamin vitro. There were significant correlations
      between work decrement (%) and betamin vivo (r=-0.72, P<0.05), VO2peak (r=-0.62,
      P<0.05), lactate threshold (LT) (r=-0.56, P<0.05) and changes in [H+]i (r=0.41,
      P<0.05). There were however, no significant correlations between work decrement
      and betamin vitro, or changes in [La-]i, or [La-]b. There were also no
      significant correlations between total work (J x kg(-1)) during the RSA test and
      betamin vitro, betamin vivo, or changes in [La-]i, pHi, [La-]b, or pHb. There
      were significant correlations between total work (J x kg(-1)) and both VO2peak
      (r=0.60, P<0.05) and LT(r=0.54, P<0.05). These results support previous research,
      identifying a relationship between RSA and aerobic fitness. This study is the
      first to identify a relationship between betamin vivo and RSA. This suggests that
      the ability to buffer H+ may be important for maintaining performance during
      brief, repeated sprints.

PMID- 15168129
TI  - Asbestos exposure and radiological abnormalities among maintenance and custodian
      workers in buildings with friable asbestos-containing materials.
AB  - OBJECTIVES: Few studies have been carried out to evaluate the respiratory effects
      of asbestos exposure of custodian and maintenance workers. METHODS: By a
      multicentre cross-sectional study, 277 custodian and maintenance employees
      working in buildings with friable asbestos-containing materials and 87 unexposed
      subjects were studied for radiological abnormalities by use of the International
      Labour Office (ILO) classification of radiographs of pneumoconiosis, in relation
      to parameters of asbestos exposure. RESULTS: The cumulative asbestos exposure
      index was generally low (fewer than 5 fibres/ml x years in 82.3% of exposed
      workers). On multivariate analysis, pleural thickening was significantly related
      to latency since onset of exposure to asbestos in exposed workers, after
      adjustment for age, body mass index and tobacco smoking. CONCLUSIONS: Asbestos
      exposure of custodian and maintenance employees in buildings with friable
      asbestos-containing materials might be associated with an excess of pleural
      thickening on chest X-rays.

PMID- 15168130
TI  - A proposed nomenclature for 15 canine-specific polymorphic STR loci for forensic
      purposes.
AB  - We performed a population study on 15 polymorphic STR loci (FH2010, FH2079, PEZ2,
      VWF.X, FH2054, FH2087Ub, FH2611, WILMS-TF, PEZ12, PEZ15, PEZ6, FH2087Ua, ZUBECA4,
      ZUBECA6, FH2132) on 131 randomly selected dogs. Alleles were identified and
      grouped according to their estimated fragment length using fixed allelic bins
      encompassing one base-pair. The allele assignment was confirmed by sequence
      analysis of homozygote and cloned heterozygote alleles. In order to develop a
      uniform repeat-based nomenclature, extensive sequence analysis was performed on a
      selection of alleles from each STR locus. The proposed nomenclature refers to the
      internationally recognised recommendations for human-specific STR loci in
      forensic applications. The 15 canine-specific STR loci were grouped into 3
      classes (simple STRs, compound STRs and complex/hypervariable STRs) according to
      their complexity and variability within the repeat structure. Finally, we
      evaluated the precision of fragment size estimation on a capillary
      electrophoresis platform and demonstrated reproducibility of fragment length
      estimation for single base-pair intermediate alleles.

PMID- 15168131
TI  - Antepartum management and neonatal outcome of triplet pregnancies.
AB  - MATERIALS AND METHODS: The maternal and neonatal outcome of 27 triplet and 1
      quadruplet gestations was studied at the University Hospital of Verona. RESULTS:
      Mean maternal age was 31.7+/-3.7 years; 24 women (85.7%) were nulliparous. Six
      (21.4%) patients had conceived spontaneously. Common maternal complications were:
      preterm labor (78.6%), anemia (57.1%), preeclampsia (25.0%). Thirteen patients
      (46.4%) had cervical cerclage, 21(75%) received tocolysis, 20 (71.4%)
      corticosteroid prophylaxis, 4 (14.3%) unfractionated heparin. All patients
      underwent Caesarean section with mean gestational age of 32+/-2.5 weeks and mean
      postoperative stay was 9 days. Three patients were treated in ICU after delivery,
      1 was hysterectomized and 6 received blood transfusions. The live newborns were
      80, the stillborns 5. Mean birth weight was 1,520+/-516 g (range 650-2,665),
      95.0% being LBW. The following neonatal complications were observed: RDS (28.7%),
      cerebral hemorrhage (26.2% of II degrees and 1.2% of III degrees ), anemia (20%),
      PDA (12.5%), ROP (6.5%), polyglobulia (3.75%), NEC (2.5%). Mean hospitalization
      time was 30.6 days (range 2-132). DISCUSSION: Iatrogenic multiple births are
      increasing as the use of assisted conception techniques expands. Gynecologists
      should be aware of maternal complications and neonatal outcome of triplet
      pregnancies and infertility management strategies should try to avoid iatrogenic
      multiple gestations.

PMID- 15168132
TI  - Extensile triradiate approach in the management of combined acetabular fractures.
AB  - INTRODUCTION: We investigated the results of combined acetabular fractures that
      were treated through the extensile triradiate approach in this study. MATERIALS
      AND METHODS: Between January 1996 and January 2001, a total of 48 acetabular
      fractures were treated surgically (mainly combined fractures). Twenty-five of the
      combined acetabular fractures that were surgically treated through the triradiate
      approach with a minimum of 2 years' follow-up were included in the study. The
      mean patient age was 42 years. There were 8 both-column, 6 T-shaped, 2 anterior
      column/posterior hemitransverse, 4 transverse with comminuted roof area, 4
      posterior wall with comminuted roof area, and 1 posterior column/posterior wall
      fracture. Associated injuries included two full-thickness chondral injuries of
      the head, one Pipkin type II fracture, five posterior and one central dislocation
      of the ipsilateral femoral head, and acetabular marginal impaction in four hips.
      The average follow-up was 44 months. RESULTS: The postoperative reduction was
      graded as excellent in 68% and imperfect in 8% of the patients. The hips were
      evaluated functionally according to the modified Postel-D'Aubigne score and rated
      as excellent in 7 patients (28%), good in 13 patients (52%), fair in 3 patients
      (12%) and poor in 2 patients (8%). There were 2 deep infections (8%), 2 avascular
      necroses of the head (8%), and 4 (16%) non-disabling heterotopic ossifications.
      CONCLUSION: Our results support the idea that open reduction with the triradiate
      approach provides good visualization and direct reduction of combined acetabular
      fractures. Its learning curve for combined fractures is shorter than that for
      single approaches and provides at least the same rate of anatomical reduction. It
      should be in the armamentarium of a surgeon dealing with such fractures.

PMID- 15168133
TI  - Pathologic fracture of the distal femur in osteitis fibrosa cystica simulating
      metastatic disease.
AB  - A 32-year-old woman sustained a minor sliding accident with moderate to severe
      pain about the left distal thigh and hip and the right shoulder. Radiographs
      showed marked osteopenia, multiple osteolytic bone lesions, and a pathologic
      fracture of the left distal femur. Surgical intervention was conducted for the
      pathologic fracture, and the pathological findings confirmed the diagnosis of
      primary hyperparathyroidism with osteitis fibrosa cystica. We report this rare
      case here because it may be mistaken for neoplastic metastatic disease on
      radiographs and bone scan. The pathologic fracture usually heals and the bone
      mineral density improves significantly within 6 months after parathyroidectomy.

PMID- 15168134
TI  - Cemented titanium stems show high migration: transprosthetic drainage system has
      no advantage over third-generation cementation technique.
AB  - INTRODUCTION: A newly developed cemented titanium stem with excellent laboratory
      results using a transprosthetic drainage system (TDS) was clinically tried for
      the first time. Prognostic radiographic methods including migration measurement
      and clinical investigation were performed for up to 7 years. MATERIALS AND
      METHODS: Twenty-two patients prospectively and consecutively received total hip
      replacement using a cemented titanium stem and a threaded Zweymuller cup. Ten
      stems (CPS) were cemented conventionally with a third-generation cementation
      technique. In 12 stems (TRIOS) a TDS was used to enhance cement mantle quality.
      Design of cup and stem was similar in all cases. RESULTS: More than 50% of all
      stems showed considerable subsidence (>1 mm at 2 years and >2.5 mm at 5 years)
      and progressive radiolucent lines ( >1 mm at 2 years). Two patients of the TRIOS
      group had to be revised at 7 years postoperatively. No significant differences
      were found in radiological parameters (migration, stem subsidence, tilting,
      occurrence of radiolucent lines) and clinical outcome between the two cementation
      techniques. All parameters indicate an unfavourable long-term survival. Use of a
      TDS did not show any significant advantages over the conventional cementation
      technique. CONCLUSION: It can be concluded that cementing titanium stems of this
      design cannot be recommended.

PMID- 15168136
TI  - Time-domain quantitation of 1H short echo-time signals: background accommodation.
AB  - Quantitation of 1H short echo-time signals is often hampered by a background
      signal originating mainly from macromolecules and lipids. While the model
      function of the metabolite signal is known, that of the macromolecules is only
      partially known. We present time-domain semi-parametric estimation approaches
      based on the QUEST quantitation algorithm (QUantitation based on QUantum
      ESTimation) and encompassing Cramer-Rao bounds that handle the influence of
      'nuisance' parameters related to the background. Three novel methods for
      background accommodation are presented. They are based on the fast decay of the
      background signal in the time domain. After automatic estimation, the background
      signal can be automatically (1) subtracted from the raw data, (2) included in the
      basis set as multiple components, or (3) included in the basis set as a single
      entity. The performances of these methods combined with QUEST are evaluated
      through extensive Monte Carlo studies. They are compared in terms of bias
      variance trade-off. Because error bars on the amplitudes are of paramount
      importance for diagnostic reliability, Cramer-Rao bounds accounting for the
      uncertainty caused by the background are proposed. Quantitation with QUEST of in
      vivo short echo-time (1)H human brain with estimation of the background is
      demonstrated.

PMID- 15168135
TI  - Clinico-pathological features of pilomyxoid astrocytoma of the optic pathway.
AB  - Five cases of pilomyxoid astrocytoma (PmA) characterized by a monophasic pattern
      with a myxoid background were selected for a clinicopathological study from 23
      cases previously diagnosed as pilocytic astrocytoma (PA). All PmA patients were
      either infants or young children (mean age 2.1 years), and all tumors were
      located in the optic chiasm/hypothalamus region. All cases received chemotherapy,
      which reduced tumor size, and the location of the tumor became confined to the
      optic chiasm. In two cases, tumor recurrence occurred 3 and 7 years after
      chemotherapy. Histology of the recurrent tumors showed the biphasic pattern of
      classical PA. Hence, we conclude that PmA might be an infantile form of PA and
      speculate that a subset of PmA in the optic pathway/hypothalamus originates from
      the optic chiasm, possibly derived from radial glia existing in the embryonic
      optic chiasm.

PMID- 15168138
TI  - Progesterone-receptor index in meningiomas: correlation with clinico-pathological
      parameters and review of the literature.
AB  - For recurrent and untreatable meningiomas alternative therapies, such as anti
      progesterone treatment, have been sought. However, the few clinical studies have
      not determined progesterone receptor (PgR) expression in most cases, and studies
      correlating quantitative PgR expression (PgR index) with clinico-pathological
      variables are scarce. The aim of our study was to assess the PgR indices in a
      consecutive series of meningiomas and correlate these values with clinico
      pathological parameters. We analyzed immunohistochemically 82 consecutive
      meningioma specimens (73 primary and nine recurrent tumors) for PgR and Ki-67
      antigen (MIB-1). The male/female ratio was 1:1.7, and median age at the time of
      surgery was 57 years (range 29-77 years). The series comprised 55 grade I
      (subtyped as 36 meningothelial, seven fibrous, nine transitional, two
      psammomatous, and one angiomatous), 23 grade II, and one grade III meningiomas.
      Nuclear immunostaining for PgR was positive in 56 meningioma specimens (71%). PgR
      index was 21.4+/-2.8% (mean +/- SE; range 0-79%). Significantly higher expression
      was found in male patients in the age group <50 years than in those > or = 60
      years and in grade I meningothelial meningiomas than in fibrous and transitional
      subtypes. There was a trend to lower PgR indices in non-benign meningiomas. Cell
      proliferation rate (MIB-1 index) was 4.4 +/- 0.4% (mean +/- SE; range 0.3-15.4%).
      Significantly higher MIB-1 indices were found in male than female patients,in
      recurrent than primary and in grade II than grade I meningiomas. We observed a
      trend to higher PgR indices in meningiomas with MIB-1 index <5%. In sum, the
      highest PgR index in our series was observed in patients under the age of 50
      years with WHO grade I meningiomas of the meningothelial subtype and low cell
      proliferation indices. If hormonal therapy has a direct action on the PgR, these
      patients should respond best to anti-progesterone treatment. We conclude that PgR
      index is variable in meningioma, depending on clinical parameters and
      histopathological features. Stratification of anti-progesterone therapy trials on
      the basis of PgR index should be considered.

PMID- 15168139
TI  - Comparison of methods for detecting Blastocystis hominis.
AB  - In order to determine the comparative sensitivity of two methods of detecting
      Blastocystis hominis and to investigate the seasonality of infection with this
      enteric protozoan parasite, the present study was conducted. In each of two 3
      month periods representing winter, spring (February-April) and summer (July
      September), 500 routine stool submissions were examined for B. hominis using
      microscopy following either formol-ether concentration or in vitro culture using
      Jones' medium. The organism was detected in 39 of the 1,000 samples investigated
      using the in vitro culture technique and in none of the samples using the formol
      ether concentration technique. In 82% of the B. hominis-positive samples, no
      concurrent bacterial or parasitic pathogens were found, and diarrhoea was the
      most commonly recorded symptom among patients. Infection was more prevalent in
      summer than in winter/spring, occurring primarily in the 71-80-year age group.
      Cysts were detected in 20.5% of positive samples, but only following Ficoll-Paque
      concentration of formol-ether concentrates. Cyst excretion was more prevalent in
      summer than in winter/spring.

PMID- 15168140
TI  - Epidemiology and characterization of Bordetella parapertussis strains isolated
      between 1995 and 2002 in and around Warsaw, Poland.
AB  - The aim of the study presented here was to analyze parapertussis infections
      occurring in the region of Warsaw, Poland, between 1995 and 2002 and to
      characterize the Bordetella parapertussis isolates using macrorestriction
      digestion of genomic DNA. Fourteen of the 17 patients with confirmed Bordetella
      parapertussis infection were between the ages of 5 and 9 years, and 14 had
      documented vaccination with the diphtheria-tetanus-pertussis whole-cell vaccine;
      for the remaining three patients vaccination data was not available. DNA
      fingerprinting performed using recommended standard methodology revealed a close
      relationship between the examined strains and reference strain ATCC 9305, thus
      confirming the conservative nature of Bordetella parapertussis.

PMID- 15168141
TI  - Effects of mode of delivery and necrotising enterocolitis on the intestinal
      microflora in preterm infants.
AB  - To investigate the effects of mode of delivery and of necrotising enterocolitis
      on the faecal microflora, 140 infants born before 33 weeks of gestation were
      followed up for symptoms of necrotising enterocolitis. Stool samples for gas
      liquid chromatography and culture were collected twice weekly, and, when
      necrotising enterocolitis was suspected, for 2 months. For each infant with
      necrotising enterocolitis (n=21), two control infants matched for birth weight
      and gestational age were selected from the remaining study population. In gas
      liquid chromatography analysis, the faecal bacterial microflora of infants born
      via caesarean section differed significantly from the gut microflora of those
      born via the vaginal route. The intestinal microflora showed a significant
      alteration in the necrotising enterocolitis group at time of diagnosis. At the
      onset of necrotising enterocolitis, faecal colonisation with Enterococcus species
      and Candida albicans was significantly more frequent in symptomatic infants than
      in controls. In infants with positive blood cultures and positive intestinal
      biopsy cultures, concomitant stool samples revealed the same microbial pathogens.
      In conclusion, the intestinal microbial colonisation in preterm infants born by
      caesarean section differs from that in preterm infants born via the vaginal
      route. A significant change in faecal microbial colonisation seems to occur at
      the onset of necrotising enterocolitis. Pathogens detected in the stools at that
      time might have a causative role in the development of the disease.

PMID- 15168142
TI  - Intrauterine device as source of pneumococcal intra-abdominal infection and small
      bowel obstruction.

PMID- 15168143
TI  - The prevalence of subclinical amyloidosis in Polish patients with rheumatoid
      arthritis.
AB  - The aims of this study were to determine the proportion of rheumatoid arthritis
      (RA) patients attending hospital in whom amyloid deposits were present in
      abdominal fat aspiration (AFA) samples, and to assess possible risk factors for
      amyloid development in RA. One -hundred and twenty-one patients (16 males, 105
      females) with RA referred to the Department of Rheumatology in Wroclaw between
      1996 and 2001 were studied regardless of RA duration or laboratory findings.
      Abdominal subcutaneous fine-needle aspiration was performed, and samples of
      adipose tissue stained with alkaline Congo red then examined by polarized light
      microscopy. The presence or absence of amyloid fat deposits (AFD) was determined
      according to whether typical apple-green birefringence was observed. Amyloid
      deposits were found in 35 (29%) patients. Amyloidosis was significantly more
      common in males and in patients with longer disease duration. Patients with AFD
      had previously undergone less treatment with disease-modifying antirheumatic
      drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD
      had previously taken methotrexate than those without AFD (25% vs 45%; p<0.01).
      Renal involvement was found in 12 of 35 patients with AFD (34%). Using the AFA
      technique, amyloid deposits were found commonly in RA patients, particularly in
      males with longer disease duration and in patients not treated intensively with
      DMARDs, especially methotrexate. AFA has potential useful application as a method
      for detecting amyloidosis before the overt occurrence of renal or other pathology
      related to amyloid deposits.

PMID- 15168144
TI  - Respiratory muscle strength but not BASFI score relates to diminished chest
      expansion in ankylosing spondylitis.
AB  - Pulmonary function is altered in ankylosing spondylitis (AS) owing mainly to the
      restriction of chest wall involvement (limited chest expansion). The objective of
      this study was to investigate the relationship between chest expansion,
      respiratory muscle strength (MIP, MEP) maximum voluntary ventilation (MVV), and
      BASFI score in patients with AS. Twenty-three male patients with definite AS and
      21 age-matched healthy male controls were recruited for the study. Patients with
      AS were assessed for functional status by BASFI. Measurement of chest expansion
      and lumbar spinal flexion (modified Schober) method was performed in all
      subjects. Pulmonary function tests were performed by spirometry. Respiratory
      muscle strength was evaluated by a mouth-pressure meter (MPM). Body mass index
      (kg/m(2)) was recorded in all individuals. Chest expansion and modified Schober
      measurement were significantly lower in AS patients (p<0.05). Pulmonary function
      tests revealed restrictive lung disease. The mean BASFI score suggested good
      functional capacity in the AS group. The respiratory muscle strength and MVV were
      also lower in AS (p<0.05). The chest expansion was correlated with MIP and MEP
      values (r=0.491; p=0.02, r=0.436; p=0.05). Chest expansion was also correlated
      negatively with disease duration (r=-0.502; p=0.03). In addition, there was no
      correlation between chest expansion and BASFI score (r=-0.076; p=0.773). This
      study demonstrates that functional status (BASFI) is not influenced by the
      limitation of chest wall movement. It may be as a result of the maintenance of
      moderate physical activity during active life in patients with AS.

PMID- 15168146
TI  - Dimensions of osteoarthritis self-management.
AB  - Our aims were to determine whether a taxonomy of self-management strategies for
      osteoarthritis could be identified, and whether the resultant dimensions of such
      a taxonomy demonstrate predictable relationships with health status indices.
      Participants (n = 117) from community-based self-help groups and a general
      rheumatology outpatient clinic completed a self-management inventory consisting
      of 11 items, answered for both the past 7 days and a day on which symptoms were
      worse than usual. Duration of symptoms, level of pain, perceived functional
      ability and self-rated health were recorded as indicators of health status. Three
      essentially identical factors were obtained for both past 7 days and worse day
      items. Resultant scales were labeled passive, complementary and active,
      respectively. Correlations with health status measures provided modest evidence
      for the construct validity of these self-management scales. Compared with a
      simple aggregate score based on the total number of strategies used, the scales
      provided a clearer understanding of the relationship between self-management and
      health. The study provided a useful extension to existing research, addressing a
      number of shortcomings identified by previous researchers. The identified self
      management dimensions offered a greater insight into the self-management choices
      of patients. Suggestions for further improvements to the measurement of self
      management are outlined.

PMID- 15168145
TI  - Increased serum levels of interleukin-8 in polyarteritis nodosa and Behcet's
      disease.
AB  - The pathogenesis of Behcet's disease (BD) and polyarteritis nodosa (PAN) is not
      yet well established. Endothelial cells have been shown to express chemokines
      that are involved in inflammatory processes. Interleukin-8 (IL-8) is a potent
      chemoattractant and activator of neutrophils. We evaluated serum IL-8 levels in
      patients with PAN and BD. We measured serum IL-8 levels in 21 patients with BD
      and 16 with PAN. Sera from 30 age-matched healthy blood donors were used as
      normal controls. Serum IL-8 levels were measured by an enzyme-linked
      immunosorbent assay (ELISA). The mean serum IL-8 level of the active BD (1522.31
      pg/ml) and that of the active PAN (654.8 pg/ml) was significantly higher than
      that of the normal controls (40.39 pg/ml, P <0.05). There was no difference in
      mean serum IL-8 levels between patients with inactive disease and normal
      controls. We found higher serum levels of IL-8 in those patients with more severe
      disease. These results suggest that IL-8 may play a role in the pathogenesis of
      PAN and/or BD. Our study also suggests a possible relation between serum IL-8
      levels and the severity of these diseases.

PMID- 15168149
TI  - Responsiveness of the DASH score in surgically treated basal joint arthritis of
      the thumb: preliminary results.
AB  - The responsiveness of the DASH score in a consecutive cohort of surgically
      treated basal joint osteoarthritis of the thumb was studied in 15 patients. The
      effect size (=1.27) and standardized response (0.84) means that, as well as the
      high correlation with patient satisfaction, the DASH score is a useful tool to
      evaluate the outcome of surgical treatment for basal joint osteoarthritis.

PMID- 15168147
TI  - The urinary excretion of pyridinoline and deoxypyridinoline during rheumatoid
      arthritis therapy with infliximab.
AB  - Rheumatoid arthritis is a systemic disease that causes inflammation and joint
      destruction. As a result of pathological destruction in bone and cartilage,
      crosslinks in collagen are resorbed more rapidly. This causes a rise in
      circulating collagen crosslink levels and their urinary excretion. In RA, apart
      from the crosslink resorption at the site of inflamed joints, there may be
      increased resorption due to general bone loss associated with disease activity.
      The aim of this study was to evaluate the influence of therapy with infliximab on
      urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPYR) as a markers
      of collagen degradation and its correlation with clinical and biochemical
      parameters of disease activity. Seventeen patients with active rheumatoid
      arthritis treated with infliximab were recruited into the study. The therapy
      resulted in the reduction in the symptoms of RA and urinary excretion of PYD and
      DPYR. The urinary excretion of PYD correlated with a number of swollen joints,
      morning stiffness, CRP and ESR. The urinary excretion of DPYR correlated during
      infliximab therapy with the number of swollen and tender joints and morning
      stiffness. The measurement of urinary excretion of PYR and DPYR may give insight
      into bone metabolism and help us to better understand the actual changes in bone
      and cartilage caused by RA and its treatment.

PMID- 15168148
TI  - Diagnostic value of antiagalactosyl IgG antibodies in rheumatoid arthritis.
AB  - Our objective in this study was to explore the diagnostic value of
      antiagalactosyl IgG antibodies in rheumatoid arthritis (RA). The study comprised
      266 Japanese patients with systemic autoimmune diseases, including 60 with RA.
      Human agalactosyl IgG was prepared enzymatically, and the serum levels of
      antiagalactosyl IgG antibodies were determined using a lectin enzyme immunoassay.
      Serum IgG and IgM rheumatoid factors (RF) were measured using laser nephelometry
      for IgM (LN-RF) and an enzyme-linked immunosorbent assay for IgG (IgG-RF).
      Antiagalactosyl IgG antibodies were significantly more common in patients with RA
      than in those without (78% vs. 18%, odds ratio (OR) 16.51, 95% confidence
      interval (CI) 8.12-33.58, p<0.0001). Patients with RA also had a higher frequency
      of LN-RF than those without RA (75% vs. 28%, OR 7.81, 95% CI 3.91-15.58, p<
      0.001). The specificity of antiagalactosyl IgG antibodies for RA was
      significantly higher than that of LN-RF (82% vs. 72%, p<0.0011). There was a
      significant correlation between titers of antiagalactosyl IgG antibodies and C
      reactive protein levels. Antiagalactosyl IgG antibodies are more specific markers
      for RA than conventional LN-RF, and may provide useful information for the
      diagnosis of RA.

PMID- 15168150
TI  - Elevated interleukin-18 levels correlated with disease activity in systemic lupus
      erythematosus.
AB  - The aim of this study was to determine the serum interleukin-18 (IL-18) levels in
      patients with systemic lupus erythematosus (SLE) and to assess their relationship
      with disease activity. Thirty-five patients with SLE and 35 age- and sex-matched
      controls were enrolled in this study. Paired serum samples were collected from
      all the patients with SLE, both at active stage before treatment and at the
      stable stage after treatment. The serum IL-18 levels were determined using ELISA
      and their correlations with the disease activity, measured using the SLE Disease
      Activity Index (SLEDAI) and laboratory parameters such as anti-dsDNA antibody,
      CH50, C3, C4, and circulating immune complex levels, were analyzed. The serum IL
      18 levels in patients with SLE were significantly higher than those in the
      controls, particularly when the disease status was active (mean+/-SD: active
      stage, 721.23+/-360.15 pg/ml; inactive stage, 343.68+/-317.78 pg/ml; controls,
      113.98+/-13.22 pg/ml, p<0.05). The IL-18 levels measured at the active stage
      before treatment correlated well with SLEDAI (r=0.41, p<0.05) and anti-dsDNA
      antibody titer (r=0.35, p<0.05). When we compared the changes of the IL-18 level
      and those of parameters reflecting the disease activity between the active stage
      and the stable stage of the disease, it was found that the changes in IL-18 level
      correlated well with the changes of SLEDAI score during the patient's disease
      course (r=0.39, p<0.05). In conclusion, the serum IL-18 levels were elevated in
      patients with SLE, and these increased levels correlated well with SLE disease
      activity.

PMID- 15168151
TI  - Bone mineral density in children with familial Mediterranean fever.
AB  - The aim of this study was to evaluate bone mineral content (BMC), serum and
      urinary bone turnover parameters in patients with familial Mediterranean fever
      (FMF), an autosomal recessive disease characterized by recurrent episodes of
      inflammation of serous membranes. Demographic characteristics and MEFV mutations
      were defined in 48 children diagnosed with FMF (23 F, 25 M; median age 7.0 years
      (3.0-10.0)). We evaluated the blood counts, acute-phase proteins and serum and
      urinary bone turnover parameters during attack-free periods. The BMC and BA (bone
      area) of vertebrae L1-L4 were measured by DEXA. Thirty-eight age-, sex- and
      ethnicity-matched healthy children constituted the control group. Mean L1-L4 BMC
      in Group I (patients with two mutations) and II (patients with no or single
      mutations) were 15.49+/-5.99 g and 15.68+/-4.89 g, respectively, both
      significantly lower than the mean L1-L4 BMC of control patients, which was
      19.59+/-6.7 g (p<0.05). Mean L1-L4 BMD in Group I, Group II and the control group
      were 0.466+/-0.066 g/cm(2), 0.487+/-0.085 g/cm(2 )and 0.513+/-0.079 g/cm(2),
      respectively. Mean z-scores in Group I, Group II and the control group were 
      1.87+/-0.74, -1.55+/-0.92 and -1.39+/-0.84, respectively. Mean L1-L4 BMD and z
      score of Group I were lower than in the control group (p<0.05). ESR and SAA
      (serum amyloid A) levels were higher in Group I patients: 28.3+/-14.5 mm/h and
      350+/-62 mg/l in Group I; and 20.5+/-11.7 mm/h and 190+/-68 mg/l in Group II,
      respectively. In conclusion, FMF patients had lower BMC, BMD and z-scores than a
      control group. We suggest that decreased BMD, BMC and z-score in FMF patients may
      be secondary to subclinical inflammation.

PMID- 15168152
TI  - Risk of infection in hospitalised children with systemic lupus erythematosus: a
      10-year follow-up.
AB  - The objective of this study was to investigate infection and sepsis in
      hospitalised children with systemic lupus erythematosus (SLE). Between 1991 and
      2000 we reviewed 72 episodes of suspected infection in 42 children with SLE from
      all hospitalised children with SLE at a medical center in Taiwan. Data comprised
      clinical and laboratory characteristics of SLE at the time of infection.
      Infections were identified and categorised as minor or major. A total of 125
      patients (110 girls, 15 boys) were admitted 557 times. Forty-two patients had
      infections, giving an infection rate of 33.6%. There were a total of 72
      infections including 20 proven infections; 61 cases of these were minor
      infections and 11 cases of these were major infections (10 cases were sepsis).
      Four patients died because of sepsis. By univariate analysis, major infection
      (sepsis) was significantly associated with a high SLE disease activity index
      score, lower complement levels and higher anti-DNA titres. In conclusion, our
      data confirm that infection is common in hospitalised children with SLE. Sepsis,
      most frequent in major infections, is associated with disease activity and causes
      significant mortality. These facts should be borne in mind when children with SLE
      are hospitalised.

PMID- 15168153
TI  - Dermatomyositis associated with lymphoproliferative disorder of NK cells and
      occult small cell lung carcinoma.
AB  - We report a case of dermatomyositis that was associated with a marked expansion
      of circulating NK cells (CD3-CD16+) with homogeneous phenotype (CD56- CD94-
      CD159a- CD244+) which satisfied the updated diagnostic criteria for the
      lymphoproliferative disorder of granular lymphocytes/NK cells. Immunosuppressive
      treatment induced remission of the dermatomyositis and decreased the number of
      circulating NK cells. However, a small cell lung carcinoma, that was occult at
      the time of the presentation of dermatomyositis, was diagnosed 10 months
      thereafter.

PMID- 15168154
TI  - Splenic marginal zone B-cell lymphoma associated with primary Sjogren's syndrome.
AB  - We describe a 67-year-old woman with primary Sjogren's syndrome who developed a
      splenic marginal zone B-cell lymphoma, and complained of a dry mouth and
      Raynaud's phenomenon. She had splenomegaly, swollen lymph nodes and monoclonal
      IgM-kappa cryoglobulin. After splenectomy, Raynaud's phenomenon had improved with
      the decrease of cryoglobulin. This is the first case of primary Sjogren's
      syndrome with splenic marginal zone B-cell lymphoma to be reported.

PMID- 15168155
TI  - Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF),
      showing RS3PE-like symptoms in extremities.
AB  - We report a patient with sarcoidosis who showed edema in the distal portion of
      all extremities, particularly the legs, as seen in remitting seronegative
      symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging
      demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and
      skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor
      (VEGF) showed a high serum level, which decreased soon after starting oral
      prednisolone, in parallel with an improvement in the limb edema. In this patient
      VEGF as well as infiltration by sarcoid granuloma in the skin might have played
      an important role in the pathogenesis of RS3PE-like symptoms in the extremities.
      When painful pitting edema is seen predominantly in the distal portion of all
      extremities, sarcoidosis as well as RS3PE should be considered as a possible
      diagnosis.

PMID- 15168157
TI  - Successful treatment of fulminant pulmonary hemorrhage associated with systemic
      lupus erythematosus.
AB  - We report a patient with systemic lupus erythematosus (SLE) who developed
      fulminant pulmonary hemorrhage. This patient also showed liver dysfunction,
      bicytopenia and hyperferritinemia, with an increase in serum levels of
      interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) at the
      onset of pulmonary symptoms, probably indicating an associated hemophagocytic
      syndrome. Despite an acute progressive course temporarily requiring mechanical
      ventilation the patient was successfully treated with continuous drip infusion of
      tacrolimus, plasmapheresis and intravenous high-dose immunoglobulin and
      corticosteroid. In this patient increased inflammatory cytokines ascribable to
      activation of macrophages and/or helper T cells were considered to play an
      important role in the pathogenesis of the pulmonary hemorrhage. Because this
      complication is frequently fatal in SLE, intensive therapy, including
      immunosuppressants and plasmapheresis, should be actively considered as early as
      possible after onset.

PMID- 15168156
TI  - Bronchiolitis obliterans organizing pneumonia associated with sulfasalazine in a
      patient with rheumatoid arthritis.
AB  - Pulmonary toxicity and blood dyscrasias are rare side effects of sulfasalazine.
      Pulmonary pathology is variable, the most common being eosinophilic pneumonia
      with peripheral eosinophilia, and interstitial inflammation with or without
      fibrosis. We here present the case of a 68-year-old female patient treated for 6
      months with sulfasalazine for rheumatoid arthritis. On laboratory examination,
      eosinophil count was 97 x 10(3) mm(3). Thorocoscopic biopsy was performed.
      Histopathologic diagnosis was bronchiolitis obliterans organizing pneumonia
      (BOOP). This is the first case in the literature to present with sulfasalazine
      induced BOOP in a patient with seronegative RA.

PMID- 15168158
TI  - Recurrent life-threatening thromboembolism and catastrophic antiphospholipid
      syndrome in a patient despite sufficient oral anticoagulation.
AB  - We report on a 32-year old female patient with primary antiphospholipid syndrome
      (PAPS) and several thromboembolic events despite stable doses of oral
      anticoagulation, good patient compliance and maintained INR values of >3. Over
      the preceding 3 years the patient had presented a wide spectrum of manifestations
      of APS, including recurrent venous and arterial thromboses, cardiac,
      gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a
      mild thrombocytopenia and the most feared manifestation of the catastrophic
      antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding
      occurred while she was anticoagulated. The clinical features appeared to be
      refractory to oral anticoagulation with phenprocoumon. They were life threatening
      on each occasion and she developed repetitive episodes of organ damage with
      cardiac insufficiency (NYHA III), pulmonary hypertension and other residual
      defects. Even during heparinization recurrent thromboembolism supervened as well
      as livedo reticularis of the extremities. Lupus anticoagulants (LAC),
      anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein-1 (beta(2)GPI)
      titers were all markedly elevated. This case report shows that recurrent episodes
      of thrombosis can occur despite seemingly adequate anticoagulation in patients
      with CAPS.

PMID- 15168160
TI  - A case of scleroderma spectrum disorder with anticentriole antibody and pulmonary
      hypertension.
AB  - We describe the case of a patient with anticentriole antibody-positive
      scleroderma spectrum disorder (SSD) who developed pulmonary hypertension. A 54
      year-old woman had noticed Raynaud's phenomenon and digital ulcers during the
      winter for the past 10 years. Although sclerodactyly was not present, digital
      ulcers, swelling of her hands, and phalangeal contracture were observed. An
      indirect immunofluorescence test revealed anticentriole antibody. Other SSc
      specific antoantibodies were negative. An echocardiogram demonstrated that the
      estimated right ventricular systolic pressure was increased to 51 mmHg. She was
      diagnosed as SSD with pulmonary hypertension. This is the first case of SSD with
      anticentriole antibody to develop pulmonary hypertension.

PMID- 15168159
TI  - Efficacy of tacrolimus in treatment of polymyositis associated with myasthenia
      gravis.
AB  - We report a patient with polymyositis (PM) associated with myasthenia gravis
      (MG). Both disorders had been controlled for around 15 years by oral prednisolone
      and a cholinesterase inhibitor following surgical removal of invasive thymoma and
      radiotherapy, but muscular weakness due to myalgia and an increase in serum
      levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared
      immediately after cessation of these drugs, which was done because the patient
      had multiple bone fractures and severe osteoporosis due to the long-term
      corticosteroid therapy. Oral tacrolimus was therefore tried, and produced an
      improvement in muscular symptoms in association with normalization of myogenic
      enzymes. PM associated with MG as in this patient might be the best indication
      for tacrolimus, considering its efficacy in MG, but this drug should also be
      actively considered as a therapeutic option in refractory cases of PM alone,
      particularly when either corticosteroids or other immunosuppressive agents are
      not usable.

PMID- 15168161
TI  - Fatal exacerbation of paraneoplastic systemic sclerosis after neoadjuvant
      chemotherapy in a breast cancer patient.
AB  - Paraneoplastic systemic sclerosis (SSc) occurs in about 3%-7% of individuals with
      SSc. There are reports of accelerated SSc syndromes associated in particular with
      breast cancer. Further exacerbations of the rheumatic condition may be induced by
      treatment of the cancer. We report a 30-year-old African-American woman with a
      contiguous diagnosis of breast cancer and paraneoplastic SSc. She was treated
      with neoadjuvant chemotherapy and developed an accelerated SSc syndrome with
      pericarditis and cardiac tamponade, with lethal results. This case report
      stresses the need for control of the rheumatic condition prior to the initiation
      of antineoplastic therapy.

PMID- 15168162
TI  - A patient with Behcet's disease who presented with simultaneous cardiac tamponade
      and central nervous system involvement.

PMID- 15168163
TI  - Difference in treatment response of osteoarthritic pain in the hip and knee.

PMID- 15168164
TI  - Lateral epicondylitis with marked soft tissue swelling in spondyloarthritis.

PMID- 15168165
TI  - Quality of marital life in patients with spondyloarthropathy.

PMID- 15168167
TI  - Subcutaneous calcification in a patient with postsurgical hypoparathyroidism.

PMID- 15168166
TI  - Miliary tuberculosis after infliximab therapy in Lebanon.

PMID- 15168169
TI  - Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2
      genes of patients from 50 Japanese breast cancer families.
AB  - We sequenced approximately 23 kb genomic regions containing all the coding exons
      and their franking introns of two breast cancer susceptibility genes, BRCA1 and
      BRCA2, of 55 individuals from 50 unrelated Japanese breast cancer families. We
      identified 55 single-nucleotide polymorphisms (SNPs) (21 in BRCA1 and 34 in
      BRCA2) containing nine pathogenic protein-truncating mutations (four in BRCA1 and
      five in BRCA2 from ten patients). Among the remaining 46 SNPs, allele frequencies
      of 40 were examined in both the breast cancer patients and 28 healthy volunteers
      with no breast cancer family history by PCR-RFLP or by direct DNA sequencing.
      Twenty-eight SNPs were common and were also found in the healthy volunteers
      and/or a SNP database. The remaining 18 were rare (allele frequency <0.05) and
      were not found in the healthy volunteers and/or the database. The pathogenic
      significance of these coding SNPs (cSNPs) remains to be clarified. The SNP
      information from this study will be useful in the future genetic testing of both
      BRCA1 and BRCA2 genes in the Japanese population.

PMID- 15168170
TI  - Genomic characterization of thermophilic Geobacillus species isolated from the
      deepest sea mud of the Mariana Trench.
AB  - The thermophilic strains HTA426 and HTA462 isolated from the Mariana Trench were
      identified as Geobacillus kaustophilus and G. stearothermophilus, respectively,
      based on physiologic and phylogenetic analyses using 16S rDNA sequences and DNA
      DNA relatedness. The genome size of HTA426 and HTA462 was estimated at 3.23-3.49
      Mb and 3.7-4.49 Mb, respectively. The nucleotide sequences of three independent
      lambda-phage inserts of G. stearothermophilus HTA462 have been determined. The
      organization of protein coding sequences (CDSs) in the two lambda-phage inserts
      was found to differ from that in the contigs corresponding to each lambda insert
      assembled by the shotgun clones of the G. kaustophilus HTA426 genome, although
      the CDS organization in another lambda insert is identical to that in the HTA426
      genome.

PMID- 15168171
TI  - Order-specific 16S rRNA-targeted oligonucleotide probes for (hyper)thermophilic
      archaea and bacteria.
AB  - New oligonucleotide probes were designed and evaluated for application in
      fluorescence in situ hybridization (FISH) studies on (hyper)thermophilic
      microbial communities--Arglo32, Tcoc164, and Aqui1197 target the 16S rRNA of
      Archaeoglobales, Thermococcales, and Aquificales, respectively. Both sequence
      information and experimental evaluation showed high coverage and specificity of
      all three probes. The signal intensity of Aqui1197 was improved by addition of a
      newly designed, unlabeled "helper" oligonucleotide, hAqui1045. It was shown that
      in addition to its function as a probe for Aquificales, Aqui1197 is suitable as a
      supplementary probe to extend the coverage of the domain-specific bacterial probe
      EUB338. In sediments from two hydrothermal seeps on Vulcano Island, Italy, the
      microbial community structure was analyzed by FISH with both established and the
      new oligonucleotide probes, showing the applicability of Arglo32, Tcoc164, and
      Aqui1197/hAqui1045 to natural samples. At both sites, all major groups of
      (hyper)thermophiles, except for methanogens, were detected: Crenarchaeota (19%,
      16%), Thermococcales (14%, 22%), Archaeoglobales (14%, 12%), Aquificales (5%,
      8%), Thermotoga/Thermosipho spp. (12%, 9%), Thermus sp. (12%, none), and
      thermophilic Bacillus sp. (12%, 8%).

PMID- 15168173
TI  - Quo vadis, orthopaedic surgeons in Japan?

PMID- 15168174
TI  - Clinical features of snowboarding injuries.
AB  - A retrospective study of 3102 injured snowboarders from 1992 to 1999 was
      undertaken using the medical records and questionnaires the patients had been
      asked to complete at the time of consultation. These cases represent all the
      injuries with medical treatment that occurred in five skiing and snowboarding
      resorts in the Nagano area. The total number of the injuries was 3243. The number
      of patients each year rapidly increased over the eight seasons. In descending
      order, the injuries were seen in the head and face, left upper extremity, spine,
      chest and abdomen, left lower extremity, right upper extremity, and right lower
      extremity. The number of head and face injuries was 829 (25%) followed by 768
      (24%) left upper extremity injuries. With regard to the type of injury, fracture
      was the most frequent injury. There were 998 fractures, of which 625 were
      fractures of the upper extremity. Contusions were frequent on the head, face,
      chest, abdomen, and pelvis. Lacerations were frequent on the head and face.
      Sprains were frequent in the lower extremities, and dislocations were seen
      frequently in the upper extremities. The sharp increase in the number of patients
      was thought to reflect the increase in the population of snowboarders in Japan.
      The reason for the high concentration of injuries to the head and upper extremity
      is thought to derive from the characteristic riding form of snowboarding, with
      both legs fixed to one short, wide board. To decrease the injuries and to develop
      snowboarding as a safe and exciting sport, snowboarders, instructors, slope
      managers, and equipment manufacturers must comprehend the patterns of
      snowboarding injuries and cooperate to devise preventive measures.

PMID- 15168175
TI  - Synovial response to intraarticular injections of hyaluronate in frozen shoulder:
      a quantitative assessment with dynamic magnetic resonance imaging.
AB  - To clarify the response of frozen shoulder (FS) to intraarticular injections of
      high-molecular-weight sodium hyaluronate (HA), a mixture of 2.5 ml of HA and 1.5
      ml of 1% lidocaine was injected into the glenohumeral joint of 11 patients with
      FS, 8 of whom received five weekly injections. The patients were assessed using
      the Japanese Orthopaedic Association shoulder score (JOA score) before the first
      injection, 1 week after the first injection, and 1 week after the final
      injection. Following each clinical evaluation, the patients underwent dynamic
      magnetic resonance imaging enhanced with Gd-DTPA, and the coefficient of
      enhancement (CE) in the glenohumeral synovium was calculated, with the examiners
      blinded to the clinical information. The JOA score tended to be greater and the
      CE smaller after injection than before injection. The changes in the CE following
      both single and repeated injections were negatively correlated with changes in
      the JOA score. Thus, clinical improvement in patients with FS was associated with
      a decrease in the CE. Because the CE depends on the degree of synovitis, the
      therapeutic effect of intraarticular HA injection for FS results, at least in
      part, from suppression of synovitis in the glenohumeral joint through an
      antiinflammatory effect.

PMID- 15168172
TI  - Does professional preventive care benefit from additional subgingival irrigation?
AB  - The effect of an oral irrigator (Water Pik, Intersante) with a subgingival tip
      (Pik Pocket Subgingival Tip, Intersante) in the reduction of gingivitis was
      investigated in a single-blind three-group study involving 45 volunteers (age
      46.2+/-10.2). All volunteers (inclusion criteria: gingivitis or a superficial
      periodontitis) were examined and underwent professional tooth cleaning at the
      first appointment. They were then randomly distributed in three groups: one group
      used the irrigator with the subgingival tip once daily with just tap water, in
      addition to their regular oral hygiene; another group also used an herbal-based
      mouth rinse (Parodontax, GlaxoSmithkline) in the water of the irrigator; a third
      group did not use an irrigator or any irrigant and therefore served as control.
      All groups received professional oral care education at each appointment. The
      investigation period was 3 months. At baseline and after 4, 8, and 12 weeks, the
      plaque index (PI, scores 0-5), gingival index (GI, scores 0-3), bleeding index
      (BI scores 0-5), and sulcus fluid flow rate (SFFR, Periotron 6000) at the
      Ramfjord teeth were scored. At baseline and after 3 months, the probing depth
      (millimeters) was measured at six surfaces of all teeth. A significant reduction
      in BI, PI, GI, probing depth, and SFFR was observed within 3 months. With all
      volunteers, however, there was no statistically significant difference (
      p>/=0.05, Wilcoxon-test, SAS 6.04) between the three groups at any time. The
      additional use of the Water Pik irrigator with the Pik Pocket subgingival
      irrigation device with or without an herbal mouth rinse showed no clinical
      benefit over professional education in oral hygiene alone.

PMID- 15168176
TI  - Meniscus allograft transplantation using posterior peripheral suture technique: a
      preliminary follow-up study.
AB  - The aim of this study was to describe the indication, planning, technique,
      rehabilitation, and clinical results after cryopreserved allograft meniscus
      transplantation. Forty consecutive patients, 33 men and 7 women (mean, 37.3 years
      of age), were evaluated at 1-year follow-up post surgery. Symptoms, patient
      satisfaction, ROM (range of motion), surgical time, blood loss, and surgical
      history were evaluated. Thirty-eight (95%) patients had previous total or partial
      meniscectomy (mean, 11.4 years ago). Preoperatively, chief complaints were knee
      joint line pain and swelling. Mean surgical time and blood loss were 123 min and
      87 g, respectively. At 12 months postsurgery, 5% and 10%, respectively,
      complained of pain and swelling; ROM was 0 degrees -132 degrees. Thirty-eight
      (95%) patients were satisfied. According to the results, meniscus transplantation
      can lead to significant pain relief and satisfaction in young symptomatic
      meniscectomized patients. However, long-term results must be obtained to prove
      the effectiveness of this technique in prevention of degenerative joint changes.

PMID- 15168177
TI  - Postradiation soft tissue sarcoma: a multiinstitutional analysis of 14 cases in
      Japan.
AB  - Radiation therapy (RT) is commonly used to treat malignant tumors, but it leads
      to side effects and complications. Postradiation sarcomas developing from a
      previously irradiated area are especially vicious to deal with, though their
      occurrence is rare. This article focuses on the clinical manifestations,
      pathological characteristics, and therapeutic effects concerning postradiation
      soft tissue sarcomas (PRSTSs). A series of 14 PRSTSs treated between 1979 and
      2000 in five hospitals in Japan were analyzed. Their histological types were
      malignant fibrous histiocytoma (eight cases), extraskeletal osteosarcoma (four
      cases), fibrosarcoma (one case), and leiomyosarcoma (one case). The primary
      diagnoses, RT history, latent period, and outcome of treatment were studied
      retrospectively. The original tumors included uterine cancer (seven cases),
      breast cancer (four cases), synovial sarcoma (one case), squamous cell carcinoma
      (one case), and Hodgkin's disease (one case). There were 13 women and 1 man, with
      ages ranging from 23 to 77 years (mean 58 years) at the time of the appearance of
      the PRSTS. RT doses ranged from 48 to 91 Gy (mean 62 Gy). The latent period from
      RT to the occurrence of the PRSTS varied from 4 to 27 years (mean 12.6 years).
      Altogether, 4 of 13 patients (31%) had recurrence of the sarcoma after resection.
      Of the 10 patients whose tumors were removed with a wide margin, one had a local
      recurrence; 3 cases were performed with a marginal margin and all 3 had a local
      recurrence. One of three who underwent RT and one of five who underwent
      chemotherapy (CT) responded. Of the 14 patients, 6 (42.9 %) survived continuously
      disease free, 2 (14.3%) died from other causes, 2 (14.3%) has an unknown outcome,
      and 4 (28.6 %) died of the disease during the follow-up period of 16-36 months
      (mean 24 months). The deaths due to other causes included an esophageal cancer
      and a wound infection. The prognosis of the PRSTS patients was not poor if the
      tumor could be removed with a wide surgical margin. Because adjuvant therapies
      including RT and CT had a poor effect on PRSTSs, the primary treatment of PRSTSs
      should be radical resection with a wide margin.

PMID- 15168178
TI  - Antegrade interlocking nailing of humeral shaft fractures.
AB  - The results of 39 humeral shaft fractures (37 patients) treated with antegrade
      locked nailing using a Russell-Taylor nail were reviewed. There were 30 acute
      fractures, 6 fractures malaligned in a hanging cast or brace, and 3 pathological
      fractures. Patient age ranged from 26 to 80 years (average, 59.7 years) and
      average follow-up was 25.7 months (range, 6-48 months). Fracture union was
      achieved in 92.3% of our cases, while shoulder function was excellent or good in
      87.2% of cases. Antegrade locked nailing offers a dependable solution for the
      treatment of humeral shaft fractures, especially in polytrauma patients and cases
      of segmental or pathological fractures. Far less satisfactory results were
      obtained in comminuted fractures of the proximal third in the humerus, especially
      in osteoporotic patients, and we therefore advocate caution with the use of
      intramedullary nailing in this type of fracture. Certain technical aspects such
      as avoiding nailing the fracture in distraction, properly countersinking the tip
      of the nail, and achieving adequate fixation stability have been found to be of
      paramount importance to reduce the incidence of delayed union/non-union rate and
      to obtain better functional results from the shoulder joint.

PMID- 15168179
TI  - Wear of ultra-high-molecular-weight polyethylene cup articulating with 22.225 mm
      zirconia diameter head in cemented total hip arthroplasty.
AB  - A number of studies have highlighted the increasing incidence of aseptic cup
      loosening with increasing depth of cup penetration by the metal head. We present
      our experience with a 22.225 mm diameter zirconia head on a 9-10 taper
      articulating with an ultra-high-molecular-weight polyethylene (UHMWPE) cup in
      cemented total hip arthroplasties. We prospectively studied the wear of the
      UHMWPE cup articulating with a 22.225 mm diameter zirconia head in cemented total
      hip arthroplasties. A total of 339 patients (153 men, 186 women, 373 hips) were
      included. The patients' mean age at surgery was 52 years (17-76 years), with 41%
      age 50 years or younger. Their mean weight was 72.4 kg (24-125 kg). At a mean
      follow-up of 4.3 years (0-8 years) the mean penetration rate of the cup was 0.03
      mm/year (0-0.51 mm/year). Altogether, 289 (77.5%) showed no measurable wear, 38
      (10.2%) had a penetration rate of 0.11 mm/year or less, 33 (8.9%) had a rate of
      0.12-0.2 mm/year, and in 13 (3.5%) the rate was more than 0.2 mm/year. Ceramic
      UHMWPE is the next stage in the evolution of total hip arthroplasty for
      addressing wear and any possible related issues.

PMID- 15168180
TI  - Femoroacetabular impingement caused by a femoral osseous head-neck bump
      deformity: clinical, radiological, and experimental results.
AB  - Femoroacetabular impingement is often associated with reduced femoral anteversion
      or an osseous bump deformity on the femoral head-neck junction. We report
      prospectively on 17 patients showing an osseous bump at the anterolateral head
      neck junction on radiography (22 hips) and typical signs of femoroacetabular
      impingement on clinical examination. Following three plans of treatment, nine
      patients (10 hips) underwent nonoperative treatment, and eight patients (12 hips)
      had surgery. In eight hips with labral defects but minor cartilage damage, the
      bump was surgically removed via trochanter flip osteotomy. Two hips were treated
      surgically through an anterior surgical approach without hip dislocation. Four
      hips with severe signs of osteoarthritis and significantly reduced range of
      motion underwent total replacement. To elucidate a local osteogenic differential
      potential, tissue specimens of the perilesional capsule were investigated
      immunohistochemically. Various antigens and protein synthesis products served to
      identify osteoblastic and progenitor cells. There was a significant improvement
      in internal rotation and pain relief in patients who underwent surgical resection
      of the osseous bump. No avascular osteonecrosis or other significant severe side
      effects were observed during follow-up. In contrast, no nonoperatively treated
      patients improved. Furthermore, immunohistochemical studies showed perilesional
      recruitment of osteoprogenitor cells.

PMID- 15168181
TI  - Biomechanical study of load transfer of the pubic ramus due to pelvic inclination
      after hip joint surgery using a three-dimensional finite element model.
AB  - We studied load-stress distribution in the pelvis using a three-dimensional
      finite element model. The results showed that the load-stress on the pubic
      superior ramus was high in the normal pelvic position without sagittal or coronal
      inclination following that of the acetabulum in the pelvis. The load-stress on
      this area was not affected by sagittal pelvic inclination, but it was affected
      significantly by coronal pelvic inclination. The superior pubic load-stress on
      the side of the longer leg was higher than that on the opposite side. The tensile
      stress on the pubic ramus on the side of the longer leg significantly increased
      compared with compressive stress. We had a patient who had an insufficiency
      fracture of the pubic ramus on the side of an overcorrected leg after hip joint
      surgery, so we examined the cause of it. Although insufficiency fractures of the
      pubic superior ramus are caused by various static and kinetic factors, the
      alternation of coronal pelvic inclination is an especially important factor in
      such fractures after hip joint surgery.

PMID- 15168182
TI  - Immunohistochemical collagen analysis of the most superficial layer in adult
      articular cartilage.
AB  - We investigated immunohistochemically the collagen type of the most superficial
      layer in 10 normal adult human articular cartilage specimens obtained from eight
      femoral heads and one each of the femoral condyle and the talus using routine
      light microscopy and polarizing microscopy. A membrane-like structure with strong
      bire-fringence covering the articular surface was observed under polarizing
      microscopy in each specimen. This structure was stained with anti-type I and anti
      type III collagen antibodies but not with anti-type II collagen antibody. This
      immunohistochemical finding was identical to that in synovial tissue. The results
      of this study confirm that the most superficial layer of adult normal articular
      cartilage consists not of type II collagen but of types I and III, and that this
      layer is absolutely independent from its deeper layer.

PMID- 15168183
TI  - Role of cytokines in gonarthrosis and knee prosthesis aseptic loosening.
AB  - Cytokines, which have been demonstrated in synovial fluids during various joint
      diseases, play an important role in mediating synovial inflammation and in
      regulating the immune response of many inflammatory processes. We studied
      synovial fluid, serum, and synovial fragments obtained from 33 patients--10
      affected by serious gonarthrosis re-quiring a prosthetic implant, 8 with knee
      prosthesis aseptic loosening, and (as controls) 15 affected by degenerative
      meniscopathies--to evaluate the degree of inflammation and level of interleukins
      (IL-2, IL-4, IL-6, IL-10) and interferon gamma secretion. Histological analysis
      revealed slightly more infiltration by inflammatory cells in the synovial tissue
      of patients with gonarthrosis and knee prosthesis aseptic loosening than in that
      of the control group, with a high prevalence of macrophages. Moreover, we
      observed enhanced production of the studied cytokines, especially in synovial
      fluid as compared to serum, indicating that in the pathological conditions
      examined the inflammatory events are mainly localized. Because the role of these
      cytokines is to modulate inflammation, better knowledge of the involvement of
      cells and their soluble mediators in articular damage could guide
      immunomodulating treatment.

PMID- 15168184
TI  - Biomechanical function of the posterior horn of the medial meniscus: a human
      cadaveric study.
AB  - Partial and total meniscectomies have been known to develop a high rate of
      osteoarthritis, but not in quantitative terms. In this study, we investigated the
      role of the posterior horn of the medial meniscus (PMM) by measuring the changes
      in the multiple degrees of freedom knee kinematics. Using a robotic/universal
      force-moment testing system, the 5-degree-of-freedom kinematics at selected
      flexion angles of human cadaveric knees (age, 35-72 years) in response to a 10
      N.m varus torque were measured. Ten knees were studied with the knee at full
      extension and at 30 degrees, 60 degrees, and 90 degrees of flexion. Each knee was
      tested in a series of four conditions: intact, with one-third of PMM resected,
      with two-thirds PMM resected, and finally with the entire PMM resected. Anterior
      tibial translation increased significantly by 1.4 mm and 4.1 mm at 30 degrees of
      knee flexion when the two-thirds and entire PMM were resected, respectively.
      Similarly, external tibial rotation significantly increased 2.2 degrees and 6.7
      degrees at 30 degrees of knee flexion with the two-thirds and entire PMM
      resected, respectively. These results suggest that resecting more than two-thirds
      of the PMM will have a significant effect on the kinematics of the knee.

PMID- 15168186
TI  - Split lesions of the peroneus brevis tendon in the Japanese population: an
      anatomic and histologic study of 112 cadaveric ankles.
AB  - Split lesions of the peroneus brevis tendon are believed to be rare and have
      received little attention in populations of Asian countries. The purpose of this
      study was to investigate the incidence of split lesions in the Japanese
      population. The peroneus tendons of 112 ankles from 30 male and 26 female adult
      human embalmed cadavers with an average age of 76.9 years (range, 55-93) were
      dissected. The presence of split lesions, determined by either thinning or
      longitudinal splitting of the peroneus brevis tendon, was examined. Forty-two
      ankles (37.5%) had split lesions, of which 21 (50%) showed a thinning appearance
      without splitting, and 12 (28.6%) had well-defined, full-thickness longitudinal
      tears. The incidence of split lesions of the peroneus brevis tendon in the
      Japanese population was similar to that in studies of the U.S. population, but
      the condition of the lesions was less severe. Although the clinical presence is
      expected to be extremely rare, we must consider a neglected split lesion of the
      peroneus brevis tendon when residual pain is observed in the retrofibular
      location.

PMID- 15168185
TI  - Histological analysis of the ligamentum flavum of patients with dialysis-related
      spondyloarthropathy.
AB  - Dialysis-related spondyloarthropathy (DRS) is a severe complication of long-term
      hemodialysis that ultimately leads to functional disability of the upper and
      lower extremities. Although the cause of this disease is still unknown, it is
      thought that amyloid deposits are involved. beta2-Microglobulin (beta2M) is a
      major component of amyloid fibrils, some of which are modified with the advanced
      glycation end-product (AGE). To clarify the pathophysiology of DRS we
      histologically examined the ligamentum flavum of the cervical spine in 15
      patients with DRS. The mean duration of hemodialysis was 20 years (12-27 years).
      In addition to the congo red stain for amyloid, beta2M and AGE were detected by
      immunohistochemical methods. Macrophages were stained with CD68 antibody. Amyloid
      deposits were found in tissues, although the extent of the stained area differed
      among the patients. Part of the amyloid deposit area was positively immunostained
      for beta2M and AGE. In 10 cases macrophages positive for CD68 infiltrated around
      the amyloid deposits. Comparing these histological findings with the dialysis
      duration, more positive staining areas for beta2M and AGE were found in the
      tissue from patients with long-term dialysis. These findings suggest that both
      beta2M and AGE play roles in the pathogenesis of DRS.

PMID- 15168188
TI  - Measurement of tension of tendon tissue based on electrical impedance.
AB  - The objective of this study was to examine whether the tension of tendon tissue
      could be measured using electrical impedance and, if so, whether the errors in
      measurement of the initial tension of a reconstructed anterior cruciate ligament
      obtained using electrical impedance were small enough to allow its use in
      clinical practice. The patella-patellar tendon-tibia complex from 35 pig knees
      was dissected. The relationship between the impedance of the patellar tendon and
      the traction stress loaded on the patellar tendon, and the repeatability of
      stress-impedance curves was examined in 15 knees. The relationship between
      impedance and strain was examined in 5, the influence of the tendon traction
      direction on tendon impedance was examined in 5, and the influence of the axial
      torsional deformation of the tendon on tendon impedance was examined in 5.
      Moreover, the relationship between the initial tension of a reconstructed
      ligament measured using electrical impedance and the load applied to the
      reconstructed ligament was examined in the remaining 5 knees. The change in
      electrical impedance of the patellar tendon due to traction was mostly caused by
      the strain of the tendon. The mean repeatability was 9.1%, the mean error due to
      differences in traction direction was 9.7%, and the mean error due to axial
      torsional deformation was 6.8%. There was a very strong correlation between the
      tension of the reconstructed ligament measured using electrical impedance and the
      force applied to the reconstructed ligament. Therefore, electrical impedance can
      be used to measure tendon tension, and it serves to measure the initial tension
      of a reconstructed ligament consisting of tendon tissue.

PMID- 15168187
TI  - Electron microscopic evaluation of two-bundle anatomically reconstructed anterior
      cruciate ligament graft.
AB  - We investigated the difference in collagen fibrils in the two-bundle anatomically
      reconstructed anterior cruciate ligament (ACL) and the one-bundle reconstructed
      ACL. Ten patients with a two-bundle anatomically reconstructed ACL using
      semitendinosus tendons (Two-ST) were followed for an average of 16 months (7-27
      months) and were compared with 15 patients with a one-bundle ACL (One-ST)
      reconstruction using hamstring tendons followed for an average of 20 months (9-39
      months). Biopsy was performed during second-look arthroscopy. The diameter of the
      collagen fibrils, their density, and the percentage of collagen fibrils were
      measured using electron micrography. We also investigated biopsy specimens of
      normal semitendinosus and gracilis tendons from 10 patients. The diameter of the
      collagen fibrils from hamstring tendons in the Two-ST (45.1 +/- 7.6 nm) was
      significantly larger than that in the One-ST (40.1 +/- 7.8 nm) ( P < 0.05). The
      diameter of the collagen fibrils in the normal hamstring tendons was
      significantly larger than that in the reconstructed ACL with hamstring tendons of
      the Two-ST and One-ST groups ( P < 0.01). The results of the study revealed that
      the diameter of collagen fibrils in the Two-ST was significantly greater than
      that in the One-ST. Hence, the tensile strength of the two-bundle graft may be
      greater than that of the one-bundle graft.

PMID- 15168189
TI  - Giant vascular leiomyoma with extensive calcification in the forearm.
AB  - Vascular leiomyoma or angioleiomyoma is a benign solitary smooth muscle tumor
      that occurs in the forearm relatively rarely. Most of these tumors are composed
      of venous vessels, but in some reports small arteries have been traced in the
      tumors. We describe a 72-year-old man who presented with a slowly enlarging mass
      in the distal forearm with extensive calcification. Our case had the following
      three peculiarities compared with common findings in patients with a vascular
      leiomyoma: (1) elderly age; (2) giant size tumor; and (3) tumor with extensive
      calcification. The ulnar artery was involved in the tumor. Simple excision of the
      tumor, including the ulnar artery, was performed. There was no recurrence and no
      cold intolerance.

PMID- 15168191
TI  - Secondary osteochondromatosis in the subacromial bursa: a report of two cases and
      review of the literature.
AB  - Osteochondromatosis is classified into primary and secondary lesions; primary
      osteochondromatosis is a tumor-like lesion, whereas secondary lesions are due to
      such joint or bursal disorders as osteoarthritis and osteochondral fractures.
      There is no clinical distinction between these two conditions. Only the
      pathological findings of loose bodies and synovium can clearly distinguish
      between them. In this report, we present two patients with secondary
      osteochondromatosis in the subacromial bursa. Both had shoulder pain and were
      treated surgically. We discuss methods of differentiating between primary and
      secondary lesions and elucidate the pathogenesis of osteochondromatosis in the
      subacromial bursa by analyzing findings for 17 shoulders with this condition
      reported in the literature. We also present two more cases. We reviewed the 12
      cases of osteochondromatosis in the literature for histopathological findings of
      loose bodies and the presence or absence of acromial osteophytes. Our findings
      suggest that osteochondromatosis of the subacromial bursa is secondary in most
      cases, and that osteocartilaginous fragments from acromial osteophytes can be
      shed into the subacromial bursa and grow into loose bodies.

PMID- 15168190
TI  - Congenital radioulnar synostosis: a case report of a probable subtype.
AB  - We present a case of bilateral congenital radioulnar synostosis in which computed
      tomography examination revealed osseous outgrowths of the ulna. Their excision
      resulted in 125 degrees range-of-motion of the forearm rotation.

PMID- 15168192
TI  - Rhabdoid transformation of recurrent meningioma in the cervical cord: a case
      report.
AB  - We report a case of persistent local recurrence of rhabdoid meningioma in the
      cervical spinal cord. Recently, the meningioma has been reported to be undergoing
      rhabdoid transformation, but the clinical course is still unclear.
      Histopathological examination of the tumor showed that it was composed of both
      meningothelial cells and rhabdoid cells. At each recurrence of the tumor, the
      population of the rhabdoid cells had increased and the ability to grow had also
      increased, confirmed by the MIB-1 labeling index. This case showed that
      phenotypic change of the cells with "rhabdoid" morphology may affect meningiomas
      and that such changes are associated with aggressive biological and clinical
      behavior. This newly classified tumor should be recognized in the differential
      diagnosis of meningioma.

PMID- 15168193
TI  - Posterolateral lumbar fusion.
AB  - Lumbar fusion has been applied to patients with lumbar instability due to
      structural defects or regressive degeneration. There are several methods for
      obtaining spinal fusion, but the gold standard is posterolateral fusion. This
      type of spinal fusion, which involves placing a bone graft in the posterolateral
      portion of the spine, has a long history and is considered by many surgeons to be
      a safe, effective method. We also have performed posterolateral lumbar fusion in
      patients with lumbar degenerative disease since 1971 and have reported good long
      term results at 10 and 20 years after surgery. Posterolateral lumbar fusion, an
      established method of lumbar fusion with less effect on adjacent segments, is
      expected to show long-term clinical success. A combination of spinal instruments
      should be employed for limited purposes, such as correcting spondylolisthesis.

PMID- 15168194
TI  - Bone morphogenetic proteins in bone tumors.
AB  - Bone morphogenetic proteins (BMPs), inducers of ectopic bone formation in vivo,
      are present in a number of osteosarcomas. BMPs are responsible for reactive bone
      formation, including periosteal reactions by normal osteoblasts, rather than
      production of tumorous osteoid by tumor cells. Osteosarcomas producing BMPs
      contain less-differentiated mesenchymal cells, resulting in a poorer prognosis
      for those patients. BMPs are also expressed in malignant fibrous histiocytomas
      (MFHs) of bone and dedifferentiated chondrosarcomas exhibiting undifferentiated
      features. However, BMPs in MFH do not show any osteoinductive activity in vivo,
      suggesting that those BMPs may be inactive forms and have additional functions
      unrelated to bone formation. Among benign bone tumors, BMPs are expressed in
      osteoid osteomas or osteoblastomas and effect reactive bone formation such as a
      surrounding sclerosis. BMPs and a BMP receptor (BMPRIB) are also detected in the
      cartilage cap in osteochondroma, suggesting that BMP signaling via BMPRIB might
      be involved in the pathogenesis of osteochondroma. Clinically, BMPs have utility
      as diagnostic and prognostic markers for characterizing the stage of
      differentiation of mesenchymal cells and mesenchymal tumors, and they may be of
      value in predicting the prognosis of sarcoma patients. This article reviews the
      accumulated information on BMPs in bone tumors, including the most recent
      findings, and discusses the biological and clinical significance of BMPs in bone
      tumors.

PMID- 15168195
TI  - HIV-1 assembly and maturation.
AB  - HIV-1 particles have been studied by structural and chemical approaches, however,
      the processes of assembly, budding and maturation are just beginning to be
      characterized, and molecular details of these processes remain poorly defined.
      This brief review summarizes some recent findings on the final steps of the HIV-1
      life cycle and touches upon some unanswered questions, particularly regarding the
      processes involved in virus maturation and infectivity.

PMID- 15168196
TI  - Transformation of rabbit lymphocytes by an Epstein-Barr virus-related herpesvirus
      from Macaca arctoides.
AB  - Herpesvirus Macaca arctoides (HVMA), an Epstein-Barr virus (EBV)-related
      herpesvirus of macaque origin, induces malignant lymphomas in rabbits. To get
      more insights into the oncogenesis of the EBV/HVMA infection the aim of the
      present study was to prove the in vitro transforming ability of HVMA for rabbit
      lymphocytes as well as human umbilical cord blood lymphocytes. As a result, B
      cell transformation could be demonstrated after infection with HVMA in all
      mononuclear cell samples of 20 rabbits. The transformation was evaluated
      microscopically and confirmed by the expression of EBV-related nuclear antigens.
      The transforming activity led to the establishment of permanent rabbit
      lymphoblastoid cell lines cultured up to more than 90 passages. The cell lines
      contained EBV-like HVMA-DNA. Interestingly, the transformed rabbit lymphocytes
      showed chromosomal abnormalities with a subtetraploid karyotype. The low extent
      of lytic cycle-dependent expression of virus capsid antigen in the established
      cell lines increased after treatment with the inducing agents iododeoxyuridine
      and mitomycin C. In contrast, no transformation could be induced after exposure
      of human umbilical cord blood lymphocytes to HVMA. The permanent rabbit
      lymphoblastoid cell lines provide a model for further studies on the role of
      EBV/HVMA in oncogenesis of lymphomas. In addition, it might be suitable for
      testing potential antiviral compounds in vitro.

PMID- 15168197
TI  - Genoprevalence in human tissues of TT-virus genotype 6.
AB  - TT virus (TTV) is a newly discovered human virus of high genotypic diversity. TTV
      is widely distributed among humans, but the possible genotype-related differences
      in TTV biology are not well known. The prevalence and amount of TTV-DNA,
      especially of genotype 6, was determined by nested-PCR in various human tissues,
      and human parvovirus B19, another ssDNA virus, was used as a reference. TTV DNA
      was detected simultaneously in bile, peripheral blood mononuclear cells (PBMC)
      and plasma of 77% subjects, in 38% skin samples, in 38% synovial samples and in
      all (100%) adenoids, tonsils and liver samples. The relative concentrations of
      TTV-DNA did not vary significantly among the different samples. Genotype 6 TTV
      DNA was detected in bile and plasma of one subject (3%), in skin and serum of one
      subject (8%) and in one liver (5%). The overall prevalence of TTV genotype 6 was
      4% in subjects and 4% in sera. TTV genotype 6 was shown to occur in human tissues
      with no obvious tissue-type or symptom specificity. Parvovirus B19 DNA was
      detected overall in 38% subjects, and bile was the only sample type tested that
      did not persistently harbour B19 DNA.

PMID- 15168199
TI  - Buthionine sulfoximine inhibits cytopathic effect and apoptosis induced by
      infection with human echovirus 9.
AB  - We studied the effect of buthionine sulfoximine (BSO) on the replication of an
      isolate of human echovirus 9 (EV9) and the apoptosis induced by it in GMK cells.
      One hundred microM BSO markedly inhibited the cytopathic effect (CPE) induced by
      EV9. BSO also significantly inhibited apoptosis induced by EV9. BSO did not
      influence replication of EV9 genome, but inhibited virion formation. These
      results suggest that the inhibition by BSO of CPE and apoptosis induced by EV9
      may be associated with the impairment of virion formation. Moreover, apoptosis
      induced by infections of human poliovirus 3, human coxsackievirus B5, A10 and
      A16, which, like EV9, belong to the genus Enterovirus, was markedly abolished by
      BSO. This finding suggests that enteroviral infections cause apoptosis through
      the activation of a common pathway that can be inhibited by BSO.

PMID- 15168198
TI  - A new potyvirus from tuberose ( Polianthes tuberosa) in China.
AB  - Tuberose plants with mild mottle symptoms, growing in a glasshouse in Hangzhou,
      China, contained virions and inclusion bodies typical of a potyvirus. The virus
      was mechanically transmitted to tuberose but not to 14 other test plant species.
      A fragment of 4607 nucleotides, corresponding to the 3'-half of a typical
      potyvirus was amplified by RT-PCR using degenerate primers and sequenced. The
      most similar sequence in the databases was that of Tuberose mild mosaic virus
      (TuMMV) from Taiwan and this was the only virus significantly related to it in
      phylogenetic analyses. The new sequence had 71.1% nt and 76.6% aa identity to
      TuMMV in the coat protein. Western blot analyses using antisera raised to
      expressed coat protein showed that the two viruses were serologically related.
      Although there are no substantial biological data to distinguish the Hangzhou
      isolate from TuMMV, the molecular difference between the two virus isolates is
      similar to, or slightly greater than, that between several pairs of well
      established potyvirus species. These results therefore suggest that the Hangzhou
      isolate should be regarded as a new member of the genus Potyvirus, and we have
      tentatively named it Tuberose mild mottle virus.

PMID- 15168200
TI  - A Tobacco necrosis virus D isolate from Olea europaea L.: viral characterization
      and coat protein sequence analysis.
AB  - A virus isolated from Olea europaea L. grown in Portugal, was identified as a
      member of the species Tobacco necrosis virus D (TNV-D, genus Necrovirus, family
      Tombusviridae), based on the molecular and serological properties of the purified
      virus particles. The genomic region encoding the coat protein (CP) of this
      isolate (named GP isolate) was amplified by RT-PCR and the cDNA was cloned and
      sequenced. The CP gene encodes a predicted protein of 269 amino acids showing
      high identity (86.2%) to TNV-D coat protein sequence. Phylogenetic analysis based
      on necroviruses CP sequences, confirmed GP as a TNV-D isolate. The alignment with
      homologous TNV-D CP sequences revealed four conserved amino acids involved in
      Ca(2+) binding as well as the plant virus icosahedral capsid protein "S'
      signature. Based on the determined nucleotide sequence, specific primers were
      designed and successfully used in RT-PCR for virus diagnosis in naturally
      infected olive trees.

PMID- 15168201
TI  - Characterization of Oita virus 296/1972 of Rhabdoviridae isolated from a
      horseshoe bat bearing characteristics of both lyssavirus and vesiculovirus.
AB  - Oita virus 296/1972 was isolated from the blood of a wild horseshoe bat,
      Rhinolophus cornutus (Temminck) in 1972. We investigated the pathogenicity of
      this virus in mice in relation to its histological, immunohistochemical and
      ultrastructural characteristics and the entire sequence of nucleoprotein gene.
      This virus caused lethal encephalitis in mice through intracerebral route. This
      susceptibility of mice was until 3 weeks of age. Immunohistochemical analysis
      using the convalescent sera obtained from survived adult mice after intracerebral
      inoculation revealed that many neurons were positive in the cytoplasm, besides no
      cross reactivity with normal and rabies virus-infected mouse brain tissues to
      this anti-sera. Ultrastructural analysis disclosed many bullet-shaped and
      enveloped virions in neurons. These morphological characteristics of the virions
      are consistent of that of viruses in the family Rhabdoviridae. Budding from
      endoplasmic membrane suggests that this virus has a similarity with lyssaviruses.
      Molecular analysis of cDNA coding a tentative nucleoprotein sequence revealed
      homology with those of viruses in the family Rhabdoviridae. Distance matrix
      analysis of this gene sequence with those of other rhabdoviruses isolated from
      mammals disclosed the discrete position of this virus in the phylogenic tree of
      rhabdoviridae infecting mammals and we renamed this virus as Oita rhabdovirus.

PMID- 15168202
TI  - Application of universal primers for identification of Foot-and-mouth disease
      virus and Swine vesicular disease virus by PCR and PCR-ELISA.
AB  - Two approaches for simultaneous identification of both Foot-and-mouth disease
      virus (FMDV) and Swine vesicular disease virus (SVDV) are described: (1) a single
      step reverse transcription-PCR with three primers and (2) a PCR-ELISA assay with
      two universal primers for genome amplification and two virus-specific probes for
      identification. These methods are based on the use of 3D gene universal PCR
      primers, the structure of which was optimized and refined due to the close
      relationship between the two viruses belonging to different genera of the
      Picornaviridae family. In procedure (1), a three-primer PCR containing one
      universal antisense primer and two virus-specific primers was shown to
      differentiate between FMDV and SVDV in one reaction, due to the different length
      of the amplified DNA fragments (600 and 340 base pairs, respectively). In
      procedure (2), the two viruses were identified by PCR-ELISA, i.e. PCR for the 3D
      gene followed by two parallel hybridizations with FMDV and SVDV-specific probes
      in microplate wells and ELISA detection. The application of universal primers
      could halve the number of PCR experiments in both cases, as compared to the usual
      virus-specific PCR procedures. Also, we investigated the 3D gene structure of
      several SVDV strains isolated at different times. No essential changes were
      detected in the regions coding for conserved motifs of the RNA-dependent RNA
      polymerase recognized by our universal primers. The multi-primer PCR was
      successfully tested on 38 FMDV and 15 SVDV strains, and the PCR-ELISA on 32 FMDV
      and 16 SVDV strains including clinical material from disease cases.

PMID- 15168203
TI  - Detection and genetic typing of type 2 porcine circoviruses in archived pig
      tissues from the UK.
AB  - Porcine circovirus 2 (PCV-2) is implicated as the causative agent of post-weaning
      multisystemic wasting syndrome (PMWS) and is also associated with porcine
      dermatitis and nephropathy syndrome (PDNS). The recent emergence of epidemic PMWS
      in the United Kingdom was predated by sporadic cases of PDNS dating back to the
      early 1980's. The aim of this study was to investigate whether PCV-2 DNA was
      present in archival tissues, and if so, to investigate the relatedness of these
      viruses with contemporary strains of PCV-2. DNA extracted from paraffin wax
      embedded tissue blocks ( n = 68), was subjected to a TaqMan polymerase chain
      reaction (PCR) targeting a fragment of ORF1 of PCV-2. Positive results were
      obtained from 41% (9/22), 31% (4/13) and 32% (8/25) of submissions from the
      1990's, 1980's and 1970's respectively. The presence of PCV-2 antigen in some of
      these tissues was confirmed by immunohistochemistry (IHC). A PCR targeting ORF2
      was used to obtain sequence data for phylogenetic analysis. Sequences from 5
      archival tissues were unique but showed high genetic identity to PCV-2 sequence
      obtained from a 2000 PDNS case. These data demonstrate that similar isolates of
      PCV-2 have been present in the UK pig population for more than 30 years.

PMID- 15168204
TI  - Analysis of genetic variability of Indian isolates of Hepatitis C virus.
AB  - The degree of genetic variability among Hepatitis C virus strains circulating in
      India is currently unknown. In order to get insight into this matter, sequence
      data obtained from the 5' non coding region from 8 patients from New Delhi were
      compared with sequences from 16 HCV isolates from different geographic locations
      of India. The phylogenetic analysis of most prevalent genotypes revealed the
      presence of novel HCV variants in type 1 strains.

PMID- 15168205
TI  - Diversity of begomovirus DNA beta satellites of non-malvaceous plants in east and
      south east Asia.
AB  - Two previous analyses of the diversity of begomovirus-associated DNA beta
      satellites focused predominantly on molecules originating from the Indian sub
      continent and southern China. They showed the satellites to group according to
      the hosts from which they were isolated, either malvaceous or non-malvaceous
      plants, and then to form sub-groups based upon geographic origin and host. In
      this study we analysed the diversity of DNA beta satellites in east and south
      east Asia. Here the satellites group by geographic location and are considerably
      more diverse than previously indicated. This probably reflects the limited
      movement of begomovirus/DNA beta complexes in this region and their subsequent
      diversification from a common ancestor to a variety of hosts.

PMID- 15168206
TI  - The complete nucleotide sequence, genome organization, and specific detection of
      Beet mosaic virus.
AB  - Beet mosaic virus (BtMV) was identified almost five decades ago but has not been
      fully characterized at the molecular level. In this study, we have determined for
      the first time the complete nucleotide sequence of BtMV genomic RNA and have
      developed a specific molecular means for its diagnosis. The viral genome of BtMV
      comprises 9591 nucleotides, excluding the 3' terminal poly (A) sequence, and
      contains a single open reading frame (ORF) that begins at nt 166 and terminates
      at nt 9423, encoding a single polyprotein of 3086 amino acid residues. A 3'
      untranslated region of 168 nucleotides follows the ORF. The deduced genome
      organization is typical for a member of the family Potyviridae and includes 10
      proteins: P1, HC-Pro, P3, 6K1, CI, 6K2, NIa-VPg, NIa-Pro, NIb and coat protein
      (CP). Nine putative protease cleavage sites were predicted computationally and by
      analogy with genome arrangements of other potyviruses. Conserved sequence motifs
      of homologous proteins of other potyviruses were found in corresponding positions
      of BtMV. BtMV is a distinct species of the genus Potyvirus with the most closely
      related species being Peanut mottle virus ( approximately 55% amino acid
      identity). Based on the nucleotide sequence obtained, we have developed a virus
      specific RT-PCR assay for accurate diagnosis and differentiation of BtMV.

PMID- 15168207
TI  - Detection of identical JC virus DNA sequences in both human kidneys.
AB  - We studied JC virus (JCV) DNA sequence diversity among kidneys derived from
      cadavers with various causes of death. The 610-bp JCV DNA sequences we evaluated
      were identical not only among specimens derived from the same kidney but also
      among those derived from both kidneys of the same cadaver. Because the left and
      right kidneys are anatomically independent, our findings suggest that the viremia
      that has been proposed to occur after primary infection distributes the same JCV
      strain to both kidneys.

PMID- 15168208
TI  - Evidence for recombination among isolates of Tobacco leaf curl Japan virus and
      Honeysuckle yellow vein mosaic virus.
AB  - Complete nucleotide sequences of Tobacco leaf curl Japan virus (TbLCJV) isolates
      from infected tomato ( Lycopersicon esculentum) plants in Nara (-[Jp2], 2764 nt; 
      [Jp3], 2761 nt), Kochi (-[Koc], 2760 nt) and Yamaguchi (-[Yam], 2758 nt)
      Prefectures, of Japan were determined. These sequences were compared with each
      other and the sequences of further begomoviruses from Japan. TbLCJV, TbLCJV
      [Jp2], TbLCJV-[Jp3], TbLCJV-[Koc], TbLCJV-[Yam], Honeysuckle yellow vein mosaic
      virus (HYVMV), Eupatorium yellow vein virus (EpYVV), EpYVV-[MNS2], EpYVV-[SOJ3],
      EpYVV-[Yam] and EpYVV-[Tob] are monophyletic. The intergenic region (IR) of
      TbLCJV has highest nucleotide sequence identity with that of HYVMV (93%) whereas
      the rest of the genomic DNA had higher identity with that of TbLCJV-[Jp2] or 
      [Jp3] (91 approximately 100%) than with that of HYVMV. In conclusion, TbLCJV has
      a chimeric genome which may have arisen by recombination between TbLCV-[Jp2] or 
      [Jp3]-like and HYVMV-like ancestors. Similarly, TbLCJV-[Yam] DNA has a hybrid
      genome, with a major parent HYVMV and minor parent TbLCJV-[Koc].

PMID- 15168209
TI  - Rapid pathotyping of Newcastle disease virus from allantoic fluid and organs of
      experimentally infected chickens using two novel probes.
AB  - A system including RNA isolation, primers and two novel oligonucleotide probes
      (NC22 and VC22) was established to rapidly pathotype Newcastle disease virus
      (NDV) from infected allantoic fluid; The sequence of the probes is: VC22, 5'
      AAGGAGGCAGAAACGCTTTATA-3'; NC22, 5'-GGGGAGACAGG GGCGCCTTATA-3'. Application
      efficacy of the probes was verified by differentiating NDV that derived from
      experimentally infected organs. NC22 and VC22 both were labeled with digoxigenin
      (DIG) and were successful in differentiating NDV strains from the infected
      allantoic fluid and organs of experimentally infected SPF chickens. The RT-PCR
      products of NDV isolates and strains were dotted onto nylon membrane and then
      hybridized with two specific probes separately. The VC22 probe is specific to
      virulent strains, and the NC22 probe is specific to avirulent strains. The
      results of hybridization coincide with viral intracerebral pathologenicity index
      (ICPI). The specificity of two probes and sensitivity of NC22 probe were
      evaluated. NC22 could detect down to 10(-8) dilution from 10(7.5) EID(50)/ml or
      800 fg of viral RNA. The system could be completed within 1 day to conduct
      experiment from clinical sample to the result of assay, and its potential
      practical application in clinical assay was discussed basing on specificity,
      sensitivity and rapidness.

PMID- 15168210
TI  - Sub-genomic replicons of Tick-borne encephalitis virus.
AB  - We constructed three sub-genomic replicons of Tick-borne encephalitis virus
      (TBEV) (Oshima REP, Oshima REP-GFP and Oshima REP-Neo) by deleting genes coding
      for structural proteins without or with insertion of green fluorescent protein
      (GFP) or Neo genes, respectively. BHK cells transfected with Oshima REP expressed
      the viral non-structural antigens in immunofluorescent and western blot analyses.
      GFP and viral antigens were co-expressed in the transfected cells with Oshima REP
      GFP. G418-resistant cells harboring Oshima REP-Neo consistently expressed the
      antigens without showing any apparent CPE. These replicons constructed in this
      study will be useful in studies on the replication, assembly and packaging of
      TBEV, and to develop vaccines and gene-delivering systems.

PMID- 15168213
TI  - Consequences of a single short lasting cerebral oligemia and the influence of
      iron injected into the substantia nigra or in the ventrolateral striatum of the
      rat. Trigger of Parkinson's disease pathogenesis?
AB  - One BCCA-phase (bilateral clamping of carotid arteria) leads to an extensive
      release of striatal dopamine with a subsequent formation of free radicals (Heim
      et al., 200b). Early investigations did not show histological damage to cerebral
      structures after 24 and 60 min duration of a BCCA phase (Melzacka et al., 1994).
      The study here turned out that oligemic damage and an increase in iron (FeCl3)
      concentration in the ventral striatum was responsible for most of the defective
      performance of the animals investigated. Striatal damaged animals were unable to
      correct their deficient performance to the same extent as was possible for
      animals which had been damaged through BCCA and FeCl3 in the substantia nigra.
      Furthermore it turn out that with the use of a comprehensive behaviour profile
      which was able to gather 22 parameters simultaneously, 15 of these parameters did
      not correspond in the performance of the controls already after BCCA alone. Since
      during the ageing process, pathological effects may occur in vulnerable
      structures not only from disturbances to cerebral blood-perfusion but also from
      enrichment of iron in vulnerable structures (Connor, 1992) the question arose
      whether this situation did not reveal pathological mechanisms that might
      triggered the early symptoms of Parkinson's disease.

PMID- 15168214
TI  - Neurotoxic potential of haloperidol in comparison with risperidone: implication
      of Akt-mediated signal changes by haloperidol.
AB  - The neurotoxicity of conventional antipsychotic drugs has emerged as a potential
      pathogenic event in extrapyramidal side effects (EPS) and in their limited
      efficacy for negative-cognitive symptoms in schizophrenic patients. The atypical
      antipsychotics, recently developed, have superior therapeutic efficacy to treat
      not only positive symptoms but negative symptoms and cognitive dysfunctions with
      much lower potentials of side effects, although the influence of atypical
      antipsychotics on the regulation of neuronal survival has been less investigated.
      It is important to clarify the effects of typical and atypical antipsychotics on
      neuronal survival and their contributions to the therapeutic development and
      understanding of the pathophysiology of schizophrenia. We measured the
      neurotoxicity of two antipsychotic drug treatments, haloperidol and risperidone,
      in primary cultured rat cortical neurons. Immunoblotting and pharmacological
      agent analyses were used to determine the signal transduction changes implicated
      in the mechanisms of the neurotoxicity. Haloperidol induced apoptotic injury in
      cultured cortical neurons, but risperidone showed weak potential to injure the
      neurons. Treatment with haloperidol also led the reduction of phosphorylation
      levels of Akt, and activated caspase-3. The D2 agonist bromocriptine and 5-HT2A
      antagonist, ketanserin attenuated the haloperidol-induced neuronal toxicity.
      Moreover, brain-derived neurotrophic factor (BDNF) reduced the caspase-3 activity
      and protected neurons from haloperidol-induced apoptosis. BDNF also reversed the
      reduced levels of phosphorylation of Akt caused by treatment with haloperidol.
      Haloperidol but not risperidone induces caspase-dependent apoptosis by reducing
      cellular survival signaling, which possibly contributes to the differential
      clinical therapeutic efficacy and expression of side effects in schizophrenia.

PMID- 15168215
TI  - CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea
      syndrome.
AB  - Assessment of serum total homocysteine (tHcy) in patients with obstructive sleep
      apnea (OSA) syndrome is highly relevant since both are strongly associated with
      stroke and cognitive dysfunction. Seven of 16 untreated OSA patients showed tHcy
      levels exceeding 11.7 micromol/l. The circadian pattern of serum tHcy in
      untreated and treated patients (p < 0.001) implied a diagnostic impact of blood
      sampling time. Treatment with continuous positive airway pressure (CPAP)
      effectively lowered tHcy levels in patients by about 30% (p < 0.005) and thus
      probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk
      for cardio-/cerebrovascular diseases.

PMID- 15168216
TI  - Pioneers of movement disorders: Georges Gilles de la Tourette.
AB  - Georges Albert Edouard Brutus Gilles de la Tourette (1857-1904), a French
      neurologist and pupil of Jean Martin Charcot at the Salpetriere hospital in
      Paris, has gained common recognition through his description of the 'Maladie des
      Tics'. This complex neuropsychiatric disorder, later known as the 'Tourette's
      syndrome', nowadays is accepted as a specific entity of movement disorders.
      Gilles had started working under Charcot (1825-1893), the first physician to
      occupy a designated chair of neurology of neuropsychiatric history, in 1884. Then
      the Salpetriere hospital was a centre of intensive research with an emphasis on
      hysteria and hypnosis. Tourette took an interest in hysteria, but also dedicated
      himself to various other neuropsychiatric disorders and to neuropathology. He
      published scientific works on epilepsia, neurasthenia and syphilitic myelitis.
      Although he devoted much time to his neuropsychiatric research and the
      publication of articles in medical journals, his career did not make significant
      progress, despite Charcot's unrestricted support. One reason was, that he
      disregarded questions, answers and problems, which were outside his interest
      fields. Hence, he was accused for having acquired an extremely filtered and one
      sided knowledge. Also, his alienated and critical behaviour, which had not helped
      him to find many friends over the years, prevented him from professional
      promotion. In 1893 an assassination attempt on Gilles de la Tourette raised
      considerable public interest: Gilles was shot in his appartement in the Rue de
      l'Universite 39 by a young woman, who had been his patient in the Salpetriere and
      who claimed that she had been hypnotized without her agreement and thereby had
      lost her mental health. However, the patient was diagnosed with a disease
      nowadays called paranoid schizophrenia and therefore hypnosis was not attributed
      to any part of the disease. Due to episodes of melancholia and phases of
      delusions of grandeur and megalomania Gilles de la Tourette was forced to leave
      his hospital appointment in 1901. These symptoms and the corresponding
      neurological signs were attributed to the paretic neurosyphilis. He was
      institutionalized to the psychiatric hospital Cery near Lausanne, Switzerland. In
      the course of the following three years he became increasingly psychotic and
      demented, suffered from epileptic seizures and finally died in hospital on 22nd
      May 1904.

PMID- 15168218
TI  - Novel dopamine releasing response of an anti-convulsant agent with possible anti
      Parkinson's activity.
AB  - We used cerebral microdialysis to assess the ability of the anticonvulsant drug
      Zonisamide (ZNS) to release striatal dopamine in 6-hydroxydopamine nigrotomized
      rats. Following exogeneously administered ZNS we measured dopamine (DA), 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in striatal
      dialysates obtained from the ipsilateral side of the nigrotomy. ZNS
      administration alone had no effect on levels of DA and its metabolites or
      rotational behavior. Administration of carbidopa-levodopa alone led to small but
      insignificant increases in rotational behavior contralateral to the side of the
      nigrotomy but no corresponding increases in indices of striatal catecholamine
      release. In contrast, if animals were preloaded with carbidopa and ZNS was co
      administered with levodopa 30 minutes later significant increases in
      contralateral rotational behavior occurred within 20 minutes of ZNS-levodopa
      injection that lasted for at least 90 minutes. In contrast to the uniform
      rotational behavioral responses observed in all our nigrotomized animals, less
      than half demonstrated neurochemical evidence of DA release. In these "responder"
      animals DOPAC levels increased 300% following carbidopa-levodopa-ZNS
      administration. We conclude that these results support previously reported
      findings and provide additional evidence that the anticonvulsant ZNS appears to
      possess anti-Parkinson's properties. ZNS could therefore be a novel agent for the
      treatment of PD that could delay the use of or reduce the amount of levodopa
      needed to treat patients with PD.

PMID- 15168217
TI  - Motor excitability and motor behaviour after modafinil ingestion--a double-blind
      placebo-controlled cross-over trial.
AB  - Modafinil is a novel vigilance-enhancing agent. We were interested if modafinil
      would also enhance motor excitability and improve motor performance and attention
      in healthy subjects. Ten volunteers received either a single oral dose of placebo
      or 200 mg modafinil. A randomized double-blind crossover design was used.
      Transcranial magnetic stimulation was employed to test intracortical inhibition,
      intracortical facilitation, the cortical silent period and to obtain stimulus
      response curves. In addition, M responses and F waves were recorded. Reaction
      time tasks, the nine-hole-peg test and the d2 attention test were also applied.
      These studies were performed prior to and 3 and 24 hours after drug ingestion.
      Modafinil did not change excitatory or inhibitory properties in the motor cortex.
      It did not alter corticospinal excitability and alpha motoneuronal excitability.
      In the modafinil group and in the placebo group, performance of the nine-hole-peg
      test and the d2 test improved to a similar extend over time. Thus, this study
      does not demonstrate significant differences between a single dose of modafinil
      and placebo in healthy subjects.

PMID- 15168219
TI  - Usefulness of switching to cabergoline from other dopamine agonists in patients
      with advanced Parkinson's disease.
AB  - Problems associated with long-term treatment of advanced Parkinson's disease (PD)
      include motor complications and psychotic and autonomic symptoms. We switched
      patients from bromocriptine (BR) or pergolide (PER) to cabergoline (CB) therapy
      and investigated CB's usefulness in alleviating such problems. Subjects were 30
      patients (mean age 68.2 years; 13 receiving BR, 17 PER) with PD complicated by
      effects of long-term treatment but in whom their dose of dopamine (DA) agonist
      was contraindicated due to adverse reactions. Patients were switched to CB over a
      2-4-week period. Hoehn-Yahr and Unified Parkinson Disease Rating Scale (UPDRS) I
      IV "on" and "off" scores improved in both the BR and PER groups. CB was not
      discontinued due to adverse reactions in any patient. In conclusion, switching to
      CB is useful in patients in whom it is problematic to increase their dose of DA
      agonist due to motor complications or psychotic symptoms of advanced PD.

PMID- 15168220
TI  - Intronic polymorphism of tryptophan hydroxylase and serotonin transporter:
      indication for combined effect in predisposition to suicide.
AB  - Indices of disturbed serotonergic neurotransmission are the most robust
      biological findings in suicide. Tryptophan hydroxylase (TPH) and 5
      hydroxytryptamine transporter (5HTt) are the main regulators of 5HT signaling.
      Owing to the assumed functionality of intronic polymorphisms of TPH (218AC) and
      5HTt (VNTR-2) genes, we investigated frequencies of concurrence of the TPH and
      5HTt genotypes containing "lower activity" alleles (CC and 1010, respectively),
      in 192 suicide victims and 377 controls. Significant differences in frequencies
      of 5HTt and TPH genotype combinations were found between suicide victims and
      control subjects (p = 0.0156), with a clear dose-effect of the suspected ("lower
      activity") genotypes (p = 0.0046). Concurrent presence of the two, allegedly
      transcriptionally less active, variants of these genes seems to be in some kind
      of relation to the increased susceptibility to suicide.

PMID- 15168221
TI  - Elevated triiodothyronine in psychopathy - possible physiological mechanisms.
AB  - We assessed a total range of peripheral thyroid hormone fractions, binding
      globulins, and thyroid-active antibodies in 37 medication-free, violent or sexual
      offenders, aged 17-45 years, to describe possible mechanisms involved in the
      thyroid metabolism of aggressive men. The ratio between T3 and T4 correlated with
      ratings of psychopathy, indicating increased peripheral deiodination as a
      biological covariate to callous personality traits. Autoimmune antibodies,
      hepatic failure, abnormal binding globulins, or substance abuse did not affect
      the association.

PMID- 15168222
TI  - Intra-operative magnetic resonance imaging in neurosurgery.
AB  - Intra-operative MRI (iMRI) has been incorporated into modern neurosurgical
      operating rooms as a guide for neurosurgical interventions for almost ten years.
      This technology has been shown to be a useful modality in brain tumour surgery
      and biopsy; its use in spine, vascular and epilepsy surgery has been evolving. It
      is particularly useful in low-grade gliomas, pituitary adenomas and pediatric
      tumors. We evaluate currently available iMRI systems and their applications in
      neurosurgery. Future possibilities related to iMRI systems are mentioned in the
      light of current advances.

PMID- 15168223
TI  - Selective diagnostic cervical nerve root block--correlation with clinical
      symptoms and MRI-pathology.
AB  - BACKGROUND: The aim of this study is to describe the method of a cervical
      selective diagnostic nerve root block (SNRB) technique and assess its ability to
      correlate clinical symptoms with MRI findings in patients with cervical radicular
      pain and a single level degenerative disease. METHODS: Twenty consecutive
      patients with cervical radiculopathy and correlating single level MRI pathology
      were studied. All patients underwent clinical investigation and neck and arm pain
      measurement with visual analog scales (VAS). The last 10 consecutive patients
      also underwent provocation with active neck motion when arm and neck pain were
      measured. They all underwent SNRB and 1 ml local-anesthesia (Mepivacaine 10
      mg/ml) was injected, with the aid of fluoroscopy, close to the nerve-root. The
      VAS estimation and clinical investigation including provocation were repeated 30
      minutes after the block. Criteria for a positive block response are a significant
      subjective pain reduction and at least 50% VAS pain reduction in the arm.
      FINDINGS: For the whole group mean VAS arm pain reductions were 86% and mean VAS
      neck pain reductions were 65%. When the results from the provocation were added
      all patients had a positive block. Eighteen were operated on by an anterior
      procedure and all 18 were free from radicular pain at follow up. INTERPRETATION:
      The block procedure seems relevant for revealing a relationship between
      radiological pathology and clinical symptoms and signs.

PMID- 15168224
TI  - Revision of vagal nerve stimulator electrodes: technical approach.
AB  - BACKGROUND: As the number of implanted vagal nerve stimulators grows, the need
      for removal or revision of the devices will become more frequent. Our purpose was
      to demonstrate the feasibility of complete removal of the vagal nerve stimulator
      electrode using microsurgical technique. METHODS: . Operative databases at the
      University of Utah (1995 through 2002), Westchester Medical Center (1995 through
      2001), and University of Arizona Health Sciences Center (1995 through 1999) were
      retrospectively reviewed. Patients who had undergone removal or revision of a
      previously placed vagal nerve stimulator electrode were identified. Patients who
      had a vagal nerve stimulator device removed but had the lead trimmed and
      incompletely removed were excluded. FINDINGS: Seven patients underwent complete
      removal of the lead. Microsurgical dissection allowed removal of the helical
      electrode from the vagus nerve without apparent physiological consequences. Four
      patients had a new electrode placed just proximal to the original lead site. The
      operative procedure required an additional 30 minutes to complete compared with
      initial device placement. The four patients who underwent replacement of the
      electrode demonstrated normal device function and lead resistance at the time of
      postoperative follow-up. Each experienced a return to prior stimulation response
      and seizure control. CONCLUSIONS: This series suggests that the electrode can be
      removed from the vagus nerve and repositioned without significant consequence in
      most cases.

PMID- 15168225
TI  - Neurosurgical management of orbital inflammations and infections.
AB  - BACKGROUND: We present an overview of the treatment and clinical outcome of 22
      orbital inflammations and infections, carried out in our center from 1991 to
      2002. METHOD: The surgical approach was determined by the location, and type of
      the lesion. Lateral orbitotomy was performed in 2 laterally located lesions, a
      transconjunctival approach in 8 medial, basal, extra-, intraconal lesions.
      Pterional intradural (5), and extradural (3) approaches were used in case of
      intracranial involvement or location in the orbital apex and optic canal. Lesions
      of the lid were operated via eyebrow incision. FINDINGS: Bacterial infections
      were confirmed in 5 cases (1 mucocele, 3 abscesses, 1 necrotizing inflammation).
      15 patients were diagnosed as chronic inflammatory pseudotumors, 6 of whom showed
      a granulomatous subtype, and 3 involvement of the optic nerve. All patients
      failed to reveal systemic disease and had a localized orbital inflammatory
      process. 7 of the patients responded rapidly to systemic corticosteroid treatment
      with no episodes of recurrence. 3 patients showed recurrence despite
      corticosteroids. CONCLUSIONS: Orbital infections are cured by antibiotic
      treatment. The course of inflammatory pseudotumor is variable and requires
      multidisciplinary treatment. Therapeutic options include surgical biopsy or
      debulking, corticosteroids, chemotherapy, and radiation therapy.

PMID- 15168226
TI  - Long-term follow-up of childhood cerebellar astrocytomas after incomplete
      resection with particular reference to arrested growth or spontaneous tumour
      regression.
AB  - BACKGROUND: The long-term prognosis for incompletely excised benign cerebellar
      astrocytomas in children remains largely unpredictable as the incidence of
      symptomatic recurrence ranges from 18 to 100%. Arrested growth and spontaneous
      tumour regression are a recognized but neglected phenomenon, the incidence and
      objective demonstration of which have received relatively little attention in the
      literature. With the aim of providing more information on this question, we
      reviewed our experience with incompletely resected benign cerebellar astrocytomas
      in children. CLINICAL MATERIAL AND METHODS: Our series consisted of 31 children
      with long-term follow-up. None had signs of type 1 neurofibromatosis (NF1).
      Histology included 22 classic pilocytic and nine diffuse astrocytomas. Seventeen
      children had symptomatic recurrence after 25 to 450 months and fourteen children
      remained in good health for 84 to 516 months. In looking for evident clinical
      differences that could help elucidate the different courses, we also examined
      recent radiographic images to assess tumour status. The literature was reviewed
      to obtain further information on nonrecurring and on regressing cerebellar
      astrocytomas after partial resection in the setting of modern surveillance
      imaging resources. FINDINGS: No differences in factors that could elucidate the
      different clinical courses were found between the two groups of children. Recent
      negative CT scans or NMR images were reported in seven cases. In two cases
      arrested growth or regression of a previously visible neoplastic remnant was
      noted. Review of the literature showed that radiographic follow-up has revealed
      arrested growth or spontaneous regression of benign cerebellar astrocytoma
      remnants in 32.5% and 14% of cases, respectively. CONCLUSIONS: As hypothesized by
      Cushing, our study shows that a large proportion of cerebellar astrocytomas do
      not progress or even regress after partial excision. This phenomenon is not
      understood and unfortunately cannot be anticipated. However, it suggests that a
      policy of "wait and see" with serial MR imaging can reasonably be recommended in
      children with cerebellar astrocytoma after partial resection, if the remnant is
      too risky to be removed by second-look surgery.

PMID- 15168227
TI  - Factors influencing seizures in adult patients with supratentorial astrocytic
      tumors.
AB  - Seizures and epilepsy in adults are important and increasingly common clinical
      problems. Despite this, the investigation of seizures in adults with astrocytic
      tumors remains a grey area. The incidence and influencing factors of preoperative
      and postoperative seizures were evaluated in 101 patients of 45 years or older
      with supratentorial astrocytic tumors. Preoperative seizures occurred in 14 (14%)
      patients. Seizures at presentation were significantly correlated with
      pathological grades of astrocytic tumors (p = 0.0318). The risk of seizures at
      presentation was greatest in patients with well-differentiated astrocytomas as
      compared with anaplastic astrocytomas (Odds ratio = 4.364, p = 0.056) or
      glioblastomas multiforme (Odds ratio = 5.673, p = 0.007). There was no
      association of preoperative seizures with age, sex, location or site of the
      tumors. Postoperative seizures occurred in 18 (18%) patients, including 8 (8/14,
      57%) recurrent seizures and 10 (10/87, 12%) late-onset seizures. Postoperative
      seizures were significantly correlated with the presence of preoperative seizures
      (p = 0.0003). The presence of preoperative seizures was potentially predictive of
      postoperative seizures when evaluated by logistic regression model (Odds ratio =
      6.650). Thirteen (72%) of 18 patients with postoperative seizures were associated
      with tumor recurrence in 7 cases, hemorrhage in 3 cases and malignant progression
      in 3 cases. There was no association of postoperative seizures with age, sex,
      location or site of the tumors, grades of tumors, type of preoperative seizures,
      duration of preoperative seizures, serum level of anticonvulsant drug, extent of
      surgery, postoperative radiation or chemotherapy. The patients with preoperative
      seizures had a higher risk of postoperative seizures and should be carefully
      monitored. Imaging examination of brain to exclude the possibilities of tumor
      recurrence or hemorrhage is warrantable in supratentorial astrocytoma patients
      with postoperative seizures.

PMID- 15168228
TI  - Association of p53 tumor suppressor gene with paraclinical and clinical
      modalities of gliomas patients in Malaysia.
AB  - BACKGROUND: Alteration of the tumor suppressor gene p53 is considered to be a
      critical step in the development of human cancer. Changes in this gene have been
      detected in a wide range of human tumours, including gliomas. In glioma, the
      presence of p53 gene alterations has been associated with worse prognosis.
      METHODS: Forty-seven Malaysian adult glioma patients of the Malay race were
      prospectively studied over a period of 3 years where the presence of p53 mutation
      using cold-SSCP method and their clinical and paraclinical response were
      correlated. FINDINGS: Among these glioma patients, p53 mutations were detected in
      12 tumors, an incidence rate of 25.5%. Mutations were found in 2 patients of
      grade II, and 5 patients both in grade III and grade IV. The sequencing results
      revealed the presence of base-substitutions (7) (58.3%) and frameshifts mutations
      (5) (41.7%). Of the base-substitutions, 57.1% were transversions and 42.9% were
      transitions. INTERPRETATION: Our analysis shows that 3 factors were associated
      with p53 mutations i.e. grade, site and consistency of tumour using univariate
      analysis although multivariate analysis revealed no positive on predictors of
      mutation. In conclusion, although p53 genetic alterations are involved in glioma
      patients in Malaysia, it has no impact on prognosis.

PMID- 15168229
TI  - Effect of hydrophilic coating on microorganism colonization in silicone tubing.
AB  - BACKGROUND: Shunt infections are one of the major causes of mortality and
      morbidity of patients with hydrocephalus. The aim of this research is to compare
      the bacterial colonization characteristics of a regular silicone elastomer shunt
      material coated with polyvinylpyrrolidone and dimethylpolysiloxane (silicone).
      METHOD: Regular coated shunt materials were compared by in-vivo and in-vitro
      methods. In the in-vitro experiment, silicone and coated material immersed and
      not immersed in vancomycin solution was treated with a certain concentration of
      Staphylococcus epidermidis. In the in-vivo study, silicone and coated material
      specimens were treated with Staphylococcus epidermidis and they were
      stereotactically placed in the lateral ventricles of the rats. One week after the
      inoculation, shunt pieces were removed and the colonies were counted by using a
      scanning electron microscope. FINDINGS: There was a statistically significant
      difference of colonization in the in-vitro groups in coated material vs.
      silicone, coated material vs. vancomycin treated silicone, vancomycin treated
      coated material vs. silicone, vancomycin treated coated material vs. vancomycin
      treated silicone. There was no statistically significant difference for
      colonization in in-vitro groups of coated material and vancomycin treated coated
      material. With in-vivo experiments we can say that, coated material catheters are
      superior than the silicone catheters in respect to colonization but after the
      bacterial colonization has occurred, the amount of colonization did not differ.
      INTERPRETATION: Coated material catheters are superior to silicone catheters and
      they prevent bacterial colonization in some respect.

PMID- 15168230
TI  - Early effects of mild brain trauma on the cytoskeletal proteins neurofilament160
      and MAP2, and the preventive effects of mexilitine.
AB  - OBJECTIVE: The aims were to investigate the early effects of graded, closed, mild
      head injury on neurofilament protein (NF160) and microtubule-associated protein-2
      (MAP2) and to examine the levels of lipid peroxidation and the impact of
      mexilitine, inhibitor of lipid peroxidation, pretreatment on tissue damage.
      MATERIAL AND METHOD: One hundred and twenty-six rats were divided into groups as
      follows: Group 1 (n = 14) were controls; group 2 (n = 56) sustained trauma alone;
      and group 3 (n = 56) were pretreated with mexilitine (50 mg/kg). Groups 2 and 3
      were subdivided into subgroups (n = 14 each), which were subjected to 100 g/cm2,
      125 g/cm2, 150 g/cm2, and 175 g/cm2 trauma forces, respectively. Two hours after
      trauma, the frontal lobes from all groups were removed and processed for lipid
      peroxidation H&E staining, immunofluorescent labelling of neurofilaments and
      microtubules with anti-NF160 and anti-MAP2 antibodies. RESULTS: Compared to
      control findings, all the trauma-only animals showed increased lipid peroxidation
      levels and the elevations paralleled the amount of force applied. Administration
      of mexilitine significantly reduced the level of lipid peroxidation. In NF160
      stainings, in group 2, the degree of impairment in axonal organization paralleled
      the different levels of force that were applied. Groups 3C and 3D (mexilitine
      pretreated) showed well-preserved axons and intact perikarya. In MAP2 stainings
      group 2 animals showed remarkably less MAP2 staining throughout the sections.
      There were no significant differences in MAP2 staining intensity or pattern among
      the group 2 subgroups. In contrast, in the sections from the group 3 animals, the
      level of MAP2 positivity was markedly preserved. CONCLUSION: In conclusion, our
      results show that the cytoskeletal proteins we investigated have different
      capacities for resisting injury, and that MAP2 is more vulnerable to injury than
      NF160. One of the reason for this cytoskeletal disruption may be increased lipid
      peroxidation. Inhibition of lipid peroxidation by pre-treatment with 50-mg/kg
      mexilitine significantly reduces the level of lipid peroxidation and may protect
      MAP2 and NF160 integrity in closed mild head injury. This protection is inversely
      proportional to the magnitude of the applied force.

PMID- 15168231
TI  - Is skull fracture necessary for developing an intradiploic pseudomeningocele as a
      complication of head injury in adulthood?
AB  - We report the case of an adult with a posttraumatic intradiploic
      pseudomeningocele which caused an expanded osteolytic skull lesion. Local pain
      and swelling, the only symptoms of the lesion, regressed after surgery.
      Intradiploic pseudomeningocele must be distinguished from intradiploic
      leptomeningeal cyst, which is of traumatic origin or arachnoid cyst and
      epidermoid cyst, which are of congenital origin. We also discuss the development
      of intradiploic pseudomeningoceleafter head trauma without skull fracture in
      adulthood and suggest a possible mechanism.

PMID- 15168233
TI  - Brain stem injury after radiofrequency trigeminal rhizotomy.

PMID- 15168234
TI  - Winter meeting 2004 of European association of neurosurgical societies, Budapest,
      Hungary, 27-29 February, 2004.

PMID- 15168232
TI  - Cerebral astroblastoma.
AB  - BACKGROUND: Astroblastoma is a rare glial tumour about which little is known.
      METHOD: We report a case of cerebral high grade astroblastoma and discuss the
      clinical, histopathological, surgical, radiological and prognostic features of
      this tumour, in the light of the pertinent literature. RESULT: Present patient
      had an initial histological diagnosis of glioblastoma multiforme. Three years
      later an histological reevaluation was performed and revealed a high grade
      astroblastoma. Our patient underwent surgical removal and radiotherapy; five
      years after the operation he is alive and without evidence of recurrence.
      INTERPRETATION: Classification and histogenesis of this tumour is still debated.
      The lack of a clinicopathological correlation makes the prognosis of this tumour
      unpredictable. The optimal management is not defined, but total resection and
      post-operative radiotherapy seem to be the effective means to treat the
      astroblastoma.

PMID- 15168238
TI  - Hemoglobin substitutes.
AB  - Orthopaedic patients frequently require blood transfusions to treat peri
      operative anemia. Research in the area of hemoglobin substitutes has been of
      great interest since it holds the promise of reducing the reliance on allogeneic
      blood transfusions. The three categories of hemoglobin substitutes are (1) cell
      free, extracellular hemoglobin preparations made from human or bovine hemoglobin
      (hemoglobin-based oxygen carriers or HBOCs); (2) fluorine-substituted linear or
      cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and
      (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most
      extensively studied and tested in preclinical and clinical trials that have shown
      success in diminishing the number of blood transfusions as well as an overall
      favorable side-effect profile. This has been demonstrated in vascular,
      cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of
      cell-free bovine hemoglobin, has been approved for clinical use in South Africa.
      These products may well become an important tool for physicians treating peri
      operative anemia in orthopaedic patients.

PMID- 15168237
TI  - Anterior thoracic posture increases thoracolumbar disc loading.
AB  - In the absence of external forces, the largest contributor to intervertebral disc
      (IVD) loads and stresses is trunk muscular activity. The relationship between
      trunk posture, spine geometry, extensor muscle activity, and the loads and
      stresses acting on the IVD is not well understood. The objective of this study
      was to characterize changes in thoracolumbar disc loads and extensor muscle
      forces following anterior translation of the thoracic spine in the upright
      posture. Vertebral body geometries (C2 to S1) and the location of the femoral
      head and acetabulum centroids were obtained by digitizing lateral, full-spine
      radiographs of 13 men and five women volunteers without previous history of back
      pain. Two standing, lateral, full-spine radiographic views were obtained for each
      subject: a neutral-posture lateral radiograph and a radiograph during anterior
      translation of the thorax relative to the pelvis (while keeping T1 aligned over
      T12). Extensor muscle loads, and compression and shear stresses acting on the
      IVDs, were calculated for each posture using a previously validated biomechanical
      model. Comparing vertebral centroids for the neutral posture to the anterior
      posture, subjects were able to anterior translate +101.5 mm+/-33.0 mm (C7-hip
      axis), +81.5 mm+/-39.2 mm (C7-S1) (vertebral centroid of C7 compared with a
      vertical line through the vertebral centroid of S1), and +58.9 mm+/-19.1 mm (T12
      S1). In the anterior translated posture, disc loads and stresses were
      significantly increased for all levels below T9. Increases in IVD compressive
      loads and shear loads, and the corresponding stresses, were most marked at the L5
      S1 level and L3-L4 level, respectively. The extensor muscle loads required to
      maintain static equilibrium in the upright posture increased from 147.2 N (mean,
      neutral posture) to 667.1 N (mean, translated posture) at L5-S1. Compressive
      loads on the anterior and posterior L5-S1 disc nearly doubled in the anterior
      translated posture. Anterior translation of the thorax resulted in significantly
      increased loads and stresses acting on the thoracolumbar spine. This posture is
      common in lumbar spinal disorders and could contribute to lumbar disc
      pathologies, progression of L5-S1 spondylolisthesis deformities, and poor
      outcomes after lumbar spine surgery. In conclusion, anterior trunk translation in
      the standing subject increases extensor muscle activity and loads and stresses
      acting on the intervertebral disc in the lower thoracic and lumbar regions.

PMID- 15168240
TI  - Laparoscopic surgery update for gastrointestinal malignancy.

PMID- 15168239
TI  - Nonoperative treatment of burst-type thoracolumbar vertebra fractures: clinical
      and radiological results of 29 patients.
AB  - The treatment of neurologically intact patients with thoracolumbar burst
      fractures is still controversial. This study was designed to evaluate the role of
      nonoperative treatment for 29 neurologically intact patients with two- or three
      column-injured thoracolumbar burst fractures. Neurologically intact patients with
      types A, B and C burst fractures were treated conservatively and divided into
      groups GI and GII, according to their column involvement, with two and three
      injured columns, respectively. Local kyphosis angle (LKA), anterior and posterior
      vertebral heights (AVH and PVH) and canal encroachment (CE) were examined for
      radiological parameters, while Denis' s work and pain criteria were used for
      clinical assessment. Remodeling determining factors of canal encroachment and the
      correlation between radiology and functionality were analyzed. The vertebral
      column deformity that occurred after the injury was stable in GI, while it was
      progressive for GII patients. There was significant remodeling of CE,
      proportional to the amount of initial CE but not related to age and radiological
      parameters. No correlation was found between radiological and functional
      parameters. None of the patients had neurological deterioration. Most of the
      functional results were satisfactory. As a result, it was concluded that
      nonoperative treatment could be an alternative method for neurologically intact
      two- and three-column-injured Denis-types A, B and C thoracolumbar burst
      fractures.

PMID- 15168241
TI  - Enhanced gastric emptying of a liquid gastric load in mice lacking
      cholecystokinin-B receptor: a study of CCK-A,B, and AB receptor gene knockout
      mice.
AB  - BACKGROUND: Although cholecystokinin (CCK) has been shown to inhibit gastric
      emptying via CCK-A receptors (CCK-ARs), the role of CCK-B receptors (CCK-BRs) has
      not been verified. We examined whether gastric emptying of a nonnutrient liquid
      load was modified in CCK-AR, BR, and ARBR gene knockout mice. METHODS: A liquid
      gastric load prepared with phenol red was administered via an orogastric tube
      (0.15 ml/mouse). The animals were killed by decapitation, and gastric emptying
      was estimated at 10 and 30 min after ingestion. The effects of the sulfated form
      of CCK-8 (CCK-8S) and of graded doses of atropine were examined. In addition, a
      proton pump inhibitor was administered to wild-type mice to examine the
      contribution of gastric acid to emptying. RESULTS: Gastric emptying was
      significantly enhanced in mice lacking CCK-BR, as compared with wild-type and CCK
      AR(-/-) mice. CCK-8S inhibited gastric emptying in mice with CCK-AR, but not in
      mice without CCK-AR. A proton pump inhibitor did not affect gastric emptying.
      Atropine dose dependently inhibited gastric emptying in all genotypes. The
      thickness of smooth muscle was comparable for all genotypes. CONCLUSIONS: The
      gastric emptying of a nonnutrient liquid load was enhanced in mice without CCK
      BR, although the precise mechanism is not known. Although cholecystokinin (CCK)
      has been shown to inhibit gastric emptying via CCK-A receptors (CCK-ARs), the
      role of CCK-B receptors (CCK-BRs) has not been verified. We examined whether
      gastric emptying of a nonnutrient liquid load was modified in CCK-AR, BR, and
      ARBR gene knockout mice.

PMID- 15168242
TI  - Topography of chronic active gastritis in Helicobacter pylori-positive Asian
      populations: age-, gender-, and endoscopic diagnosis-matched study.
AB  - BACKGROUND: The incidence and mortality of gastric cancer is high among Japanese
      and Chinese populations but extremely low in Thailand and low in Vietnam. The aim
      of this study was to compare the degree of corpus-predominant gastritis, which is
      considered to be one of risk factors of gastric cancer, in Helicobacter pylori
      positive Asian adult populations. METHODS: H. pylori-positive Chinese (Beijing
      and Fuzhou), Thai, and Vietnamese patients were paired with Japanese patients by
      age, gender, and endoscopic diagnosis to compare the ratio of corpus gastritis to
      antrum gastritis (C/A ratio) (105, 85, 195, and 154 pairs, respectively).
      RESULTS: The Japanese C/A ratio was significantly higher than that in other
      groups. Corpus-predominant gastritis (C/A ratio > 1.00) was characteristic in
      aged Japanese and Chinese (Fuzhou), but Chinese (Beijing), Thai, and Vietnamese
      were antrum predominant (C/A ratio < 1.00) in every age group except for the
      Vietnamese over-70 group. There was a similarity between degree of H. pylori
      colonization and neutrophil activity score. CONCLUSIONS: Corpus-predominant
      gastritis was found in aged Japanese and Chinese (Fuzhou) and antrum-predominant
      gastritis was found in Chinese (Beijing), Thai, and Vietnamese patients. These
      results correlate with the low incidence of gastric cancer in Thai and Vietnamese
      populations. The incidence and mortality of gastric cancer is high among Japanese
      and Chinese populations but extremely low in Thailand and low in Vietnam. The aim
      of this study was to compare the degree of corpus-predominant gastritis, which is
      considered to be one of risk factors of gastric cancer, in Helicobacter pylori
      positive Asian adult populations.

PMID- 15168243
TI  - A pilot study of imatinib mesylate (STI571) on gastrointestinal stromal tumors in
      Japanese patients.
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common type of
      nonepithelial tumor in the gastrointestinal tract. The gastrointestinal stromal
      tumor is defined immunohistologically as a c-Kit-positive tumor. For those GISTs
      that are malignant, the only effective treatment modality has been surgical.
      Early clinical reports have shown that imatinib mesylate (STI571) produces
      substantial anticancer activity in patients with metastatic or unresectable GIST.
      METHODS: Nine Japanese patients who were found clinically and
      immunohistochemically to have inoperable GISTs were entered into this study.
      These patients were given 400 mg STI571 orally once daily. We then evaluated the
      tumor response and the safety of the drug. RESULTS: Five of the nine patients
      achieved partial responses, two had stable disease, and two had progressive
      disease. The main side effects were skin rash, edema, periorbital edema,
      diarrhea, nausea, and vomiting. Mild anemia, leukocytopenia, and neutropenia were
      also noted. No patients required dose reduction or cessation because of adverse
      events. CONCLUSIONS: This study demonstrates that STI571 might be an active agent
      against malignant GIST in Japanese patients with manageable toxicities.
      Gastrointestinal stromal tumor (GIST) is the most common type of nonepithelial
      tumor in the gastrointestinal tract. The gastrointestinal stromal tumor is
      defined immunohistologically as a c-Kit-positive tumor. For those GISTs that are
      malignant, the only effective treatment modality has been surgical. Early
      clinical reports have shown that imatinib mesylate (STI571) produces substantial
      anticancer activity in patients with metastatic or unresectable GIST.

PMID- 15168244
TI  - Self-expandable metallic stent placement as palliative treatment of obstructed
      colorectal carcinoma.
AB  - BACKGROUND: Stent placement in palliation of unresectable colon cancer is an
      alternative to surgical treatment. The through-the-scope stent for the exclusive
      treatment of colorectal cancer is not available in Japan. This report describes
      the use of an esophageal stent and the technical modifications required for its
      success in the treatment of colorectal strictures. We describe various technical
      strategies for colorectal stent placement and report on the outcomes. METHODS:
      Medical records of patients who underwent palliative colonic stenting between
      June 1997 and March 2003 were reviewed retrospectively, and the clinical outcome
      was evaluated. RESULTS: Insertion of a metallic esophageal stent was attempted in
      12 patients (mean age, 73.0 years; 5 male, 7 female). Location of the stricture
      was in the rectum in 4 patients and in the sigmoid, descending, or transverse
      segments of the colon in 5, 1, and 2 patients, respectively. Two patients had
      recurrent colon cancer after surgery. The remaining 10 patients did not undergo
      surgery. Stent placement was technically successful in 11 patients, giving a
      technical success rate of 92%. Following successful stent placement, all but 1
      patient obtained clinical success, generating a clinical success rate of 83%.
      Late complications occurred in 4 patients and included 2 migrations, 2 bleeds,
      and 1 obstruction. The complication rate of the procedure was 33.3%. There was no
      mortality or severe complications. The median survival period was 120 days.
      CONCLUSIONS: Stent placement can be considered safe and effective palliation for
      unresectable colorectal cancer. With technical modification of an esophageal
      stent, this procedure is now feasible. Stent placement in palliation of
      unresectable colon cancer is an alternative to surgical treatment. The through
      the-scope stent for the exclusive treatment of colorectal cancer is not available
      in Japan. This report describes the use of an esophageal stent and the technical
      modifications required for its success in the treatment of colorectal strictures.
      We describe various technical strategies for colorectal stent placement and
      report on the outcomes.

PMID- 15168245
TI  - Effects of antihyperlipidemic agents on hepatic insulin sensitivity in perfused
      Goto-Kakizaki rat liver.
AB  - BACKGROUND: We previously reported that the Goto-Kakizaki (GK) rat, an animal
      model of type 2 diabetes, has hepatic insulin resistance using a perfused rat
      liver model. Pioglitazone, eicosapentaenoic acid (EPA), and fenofibrate are
      antihyperlipidemic agents and improve glucose tolerance. There have been few
      studies showing that these agents directly improve hepatic insulin sensitivity in
      type 2 diabetes mellitus. The aim of this study was to explore the effects of
      these agents on hepatic insulin sensitivity directly using a perfused GK rat
      liver model. METHODS: GK rats were treated with oral pioglitazone (6 or 10 mg/kg
      body weight), EPA (1 or 2 g/kg body weight), or fenofibrate (30 mg/kg body
      weight) for 2 weeks. Livers were perfused in situ with glucagon or with glucagon
      and insulin, and hepatic glucose outputs were measured. RESULTS: In the
      pioglitazone-treated GK rats, blood glucose levels were significantly decreased.
      In the pioglitazone- and EPA-treated GK rats, insulin infusion significantly
      attenuated hepatic glucose output stimulated by glucagon. In the fenofibrate
      treated GK rats, fat deposits in the hepatocytes were decreased, and glucose
      output elicited by glucagon was significantly decreased compared with that in the
      untreated GK rats, whereas insulin infusion did not affect glucose output by
      glucagon. CONCLUSIONS: These findings suggest that pioglitazone and EPA may
      improve glucose tolerance by directly increasing hepatic insulin sensitivity,
      while fenofibrate may improve glucose tolerance by improving hepatic glycogen
      metabolism in the GK rats. We previously reported that the Goto-Kakizaki (GK)
      rat, an animal model of type 2 diabetes, has hepatic insulin resistance using a
      perfused rat liver model. Pioglitazone, eicosapentaenoic acid (EPA), and
      fenofibrate are antihyperlipidemic agents and improve glucose tolerance. There
      have been few studies showing that these agents directly improve hepatic insulin
      sensitivity in type 2 diabetes mellitus. The aim of this study was to explore the
      effects of these agents on hepatic insulin sensitivity directly using a perfused
      GK rat liver model.

PMID- 15168246
TI  - High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver
      injury by reducing proinflammatory cytokines in mice.
AB  - BACKGROUND: The extracellular matrix component hyaluronan (HA) modulates the
      production of various cytokines and chemokines by activated inflammatory cells.
      In this study, we investigated whether exogenous administration of HA influences
      T-cell-mediated liver injury and cytokine production. METHODS: Liver injury was
      induced by administration of concanavalin A (Con A) or D
      galactosamine/lipopolysaccharide (GalN/LPS), and 0.05%-0.35% (v/v) HA (MW 250,
      470, 780, 900, and 1200 kDa) was administered intravenously 18 h before Con A or
      GalN/LPS injection. Plasma ALT level was determined enzymatically and plasma
      cytokine levels were determined by ELISA. RESULTS: The elevated plasma levels of
      ALT at 8 h after Con A and at 7 h after GalN/LPS injection were significantly
      decreased by pretreatment with high molecular weight HAs (780, 900, and 1200 kDa)
      but not low molecular weight HAs (250 and 470 kDa). High molecular weight HA (900
      kDa) significantly reduced plasma tumor necrosis factor-alpha, interferon gamma,
      macrophage inflammatory protein 2, and interleukin 4 levels after Con A
      injection. However, this inhibitory effect on plasma cytokines was not observed
      with low molecular weight HA (250 kDa) pretreatment. CONCLUSIONS: The present
      results suggest that high molecular weight but not low molecular weight HA
      prevents liver injury by reducing proinflammatory cytokines in a T-cell-mediated
      liver injury model. The extracellular matrix component hyaluronan (HA) modulates
      the production of various cytokines and chemokines by activated inflammatory
      cells. In this study, we investigated whether exogenous administration of HA
      influences T-cell-mediated liver injury and cytokine production.

PMID- 15168247
TI  - Alteration of the p14(ARF) gene and p53 status in human hepatocellular
      carcinomas.
AB  - BACKGROUND: The INK4a/ARF locus encodes p16INK4a and p14ARF, both of which are
      crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16INK4a and
      p53/ARF. Inactivation of RB/p16INK4a was frequently reported, but alterations of
      the p14ARF gene in hepatocellular carcinoma (HCC) in the Japanese population have
      been insufficiently analyzed. METHODS: To determine the role of p53/ARF
      alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression,
      deletion, mutation, and promoter hypermethylation of the p14(ARF) gene;
      alterations of p53 were also analyzed in the same series of HCCs. RESULTS:
      Homozygous deletion, spanning from exon 1 beta to exon 2, was found in 1 HCC
      mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation
      was detected. All 3 HCCs with p14(ARF) alteration were well differentiated.
      Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53
      alteration; however, only 1 of the tumors with p53 alteration was well
      differentiated. TaqMan polymarase chain reaction (PCR) indicated that the
      expression of p14(ARF) in HCCs was higher than in that in all but three of the
      corresponding non-tumorous tissues ( P < 0.0001), and increased expression of
      p14(ARF) seemed to be associated with poorly differentiated phenotype. Absence of
      p14(ARF) expression was seen in only one HCC, with homozygous deletion of the
      p14(ARF) gene. CONCLUSIONS: Compared with p53 alteration, p14(ARF) alteration
      does not occur frequently, but may play a role in a subset of Japanese HCCs in
      the early stage of hepatocarcinogenesis. On the other hand, overexpression of
      p14(ARF) was frequently observed in HCC, especially in poorly differentiated
      tumors, probably reflecting oncogenic stimuli in these tumors. The INK4a/ARF
      locus encodes p16(INK4a) and p14(ARF), both of which are crucial for two tumor
      suppressor pathways, retinoblastoma (RB)/p16(INK4a) and p53/ARF. Inactivation of
      RB/p16(INK4a) was frequently reported, but alterations of the p14(ARF) gene in
      hepatocellular carcinoma (HCC) in the Japanese population have been
      insufficiently analyzed.

PMID- 15168248
TI  - Chemotherapy using 5-fluorouracil, mitoxantrone, and cisplatin for patients with
      advanced hepatocellular carcinoma: an analysis of 63 cases.
AB  - BACKGROUND: We evaluated the anti-tumor efficacy and toxicity of 5-fluorouracil
      (5-FU), mitoxantrone, and cisplatin (FMP) in patients with advanced
      hepatocellular carcinoma (HCC), and conducted an analysis of the prognostic
      factors for response to such therapy and patient survival. METHODS: Sixty-three
      patients suffering from unresectable and non-embolizable HCC and who had
      objectively measurable tumors, adequate liver and renal function, and adequate
      bone-marrow reserve were enrolled in this study. The therapeutic regimen
      consisted of cisplatin 80 mg/m(2) and mitoxantrone 6 mg/m(2) intravenously on day
      1, and 5-FU 450 mg/m(2) per day continuous infusion for a period of 5 days.
      Univariate and multivariate analyses of patient and disease characteristics were
      used to identify factors predicting patient response and survival. RESULTS: The
      objective response was 23.8% (95% confidence interval [CI], 13.0-34.6%). The
      median survival for all 63 patients was 4.9 months (95% CI, 3.2-6.6 months). The
      median time to progression was 2.5 months (95% CI, 1.7-3.3 months). Multivariate
      analysis identified only performance status ( P = 0.050) and liver tumor size ( P
      = 0.012) as being significantly related to patient objective response.
      Independent variables associated with a better patient survival included: the
      absence of ascites ( P = 0.003), a lower total bilirubin level ( P = 0.026), and
      the patient being a positive chemotherapy responder ( P = 0.009). CONCLUSIONS:
      The response rate to an FMP regimen was still unsatisfactory, although a specific
      subgroup of patients (good performance status, smaller liver tumor mass, good
      liver reserve, and distant metastasis) may benefit from this regimen.We evaluated
      the anti-tumor efficacy and toxicity of 5-fluorouracil (5-FU), mitoxantrone, and
      cisplatin (FMP) in patients with advanced hepatocellular carcinoma (HCC), and
      conducted an analysis of the prognostic factors for response to such therapy and
      patient survival.

PMID- 15168249
TI  - Pachydermoperiostosis associated with juvenile polyps of the stomach and gastric
      adenocarcinoma.
AB  - Pachydermoperiostosis (PDP) is a rare syndrome, and the presence of digital
      clubbing, radiographic periostosis, and coarse facial features are the main
      diagnostic criteria. Here, we report patient with the primary form of PDP in whom
      juvenile polyps and gastric cancer developed within 9 years of follow-up. A 27
      year-old Japanese man, diagnosed as having the primary form of PDP at 14 years of
      age, was referred to our department for assessment of chronic anemia. On upper
      gastrointestinal endoscopic examination, multiple polypoid lesions with a huge
      polyp were found in the stomach, and biopsy findings indicated juvenile polyps,
      although no polypoid lesion had been present at the age of 18 years. Bleeding
      from these polyps was suspected, and endoscopic mucosal resection of the polypoid
      lesions was performed. Histology of the huge polyp showed hamartoma, adenoma, and
      adenocarcinoma in part. This is the first case report of the primary form of PDP
      associated with gastric cancer. In this patient, juvenile polyps and gastric
      cancer developed within 9 years of follow-up, indicating that the primary form of
      PDP may be a high risk factor for gastric cancer, and that periodical follow-up
      with upper gastrointestinal endoscopy is important.

PMID- 15168250
TI  - Dieulafoy's vascular malformation of the jejunum: first case report of
      laparoscopic treatment.
AB  - A case of Dieulafoy's vascular malformation of the jejunum treated by
      laparoscopic surgery is described. The patient was a 31-year-old-woman who had
      complained of melena and had severe anemia needing blood transfusion. Angiography
      revealed microaneurysms and hypervascularity of the jejunum in the area between
      the first and second jejunal arterial fields. Laparoscopic partial resection of
      the jejunum was performed. The resected specimen was histologically diagnosed as
      Dieulafoy's vascular malformation. Since the operation, the patient has been free
      of melena and anemia. Small-intestinal Dieulafoy's vascular malformation is rare,
      as only 41 cases have been reported during the past three decades. Almost two
      thirds of the patients were under 40 years old. Most of the patients complained
      of melena. The lesion was preoperatively identified in 14 of the 41 patients,
      while angiography was useful to define the lesion. Thirty-six of 37 patients for
      whom treatment methods were reported were surgically treated. While there are
      various treatment methods for intestinal bleeding, a surgical operation is often
      needed. When the disease location is obvious, treatment with laparoscopic surgery
      can reliably produce good results, in terms of its rate of cure, minimal
      invasiveness, and better cosmetic effect.

PMID- 15168251
TI  - Perforated duodenal diverticulum successfully diagnosed preoperatively with
      abdominal CT scan associated with upper gastrointestinal series.
AB  - Although duodenal diverticulum is not uncommon, precise preoperative diagnosis is
      occasionally difficult. We report a patient with perforated duodenal diverticulum
      successfully diagnosed preoperatively by an upper gastrointestinal series
      followed by abdominal computed tomography (CT) scanning. An 81-year-old Japanese
      woman visited a local hospital because of right-sided abdominal pain. Physical
      examination revealed diffuse muscle guarding localized in the entire right-side
      of the abdomen indicative of peritonitis. While plain abdominal X-ray film
      revealed no free air, abdominal ultrasound and abdominal CT scanning revealed
      fluid collection and gas in the anterior perirenal space. An emergency upper
      gastrointestinal series, using water-soluble contrast media, demonstrated
      multiple diverticula in the descending portion and the horizontal portion of the
      duodenum. Leakage of the contrast material was found by the upper
      gastrointestinal series followed by the abdominal CT scanning, suggesting that
      the peritonitis was caused by the perforated duodenal diverticulum, and an
      emergency laparotomy was performed. The diverticulum in the descending portion of
      the duodenum was mobilized from the retroperitoneum and complete resection and
      peritoneal drainage were performed. The resected specimen showed that the
      diverticulum was 42 x 23 mm in size, and two separate sites of perforation were
      identified. The present case suggests that upper gastrointestinal series followed
      by CT scan is useful for the preoperative diagnosis of perforated duodenal
      diverticulum.

PMID- 15168252
TI  - Multiple hepatic peribiliary cysts with cirrhosis.
AB  - Multiple hepatic peribiliary cysts were found in three autopsy cases of patients
      who had had underlying liver diseases and obstructive jaundice. Macroscopically,
      the cysts were visible and present exclusively in the hepatic hilum and larger
      portal tracts. Histologically, the cysts were of varying size and were lined by a
      single layer of cuboidal or flattened epithelial cells without atypia. Intimate
      association between the cysts and peribiliary glands was found in the walls of
      large bile ducts. All three cases were associated with liver cirrhosis in
      patients with portal hypertension, and two of the patients had also had
      hepatocellular carcinoma. These findings support the previous assumption that
      multiple hepatic peribiliary cysts may be closely related to a portal
      hypertensive condition. Although peribiliary cysts have been considered to be
      clinically asymptomatic in general, in one of our patients, the cystic dilatation
      appeared to have been responsible for the progression of obstructive jaundice.

PMID- 15168253
TI  - Hepatocellular carcinoma with nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign
      disease. However, it has been recently revealed that NASH could lead to
      irreversible liver disease in some patients. We report an unusual case of
      hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history
      of alcohol consumption, drug use, or blood transfusion. He was negative for all
      serological viral markers and autoantibodies. In addition, he was obese (body
      mass index [BMI], 30.75 kg/m(2)) and had type 2 diabetes mellitus. A liver biopsy
      specimen showed moderate steatosis with necroinflammatory changes, ballooning
      degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular
      regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver
      tumor, measuring 19 mm in diameter, was detected in segment 6. A tumor biopsy
      specimen revealed well-differentiated HCC, and imaging modalities confirmed the
      characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were
      reported. In all patients with NASH and HCC, cirrhosis was present. Patients with
      NASH and cirrhosis may progress to HCC, and regular screening, based on tumor
      markers and imaging modalities, is needed to detect HCC in patients with NASH and
      cirrhosis.

PMID- 15168254
TI  - Comparison of argon plasma coagulation and paravariceal injection sclerotherapy
      with 1% polidocanol in mucosa-fibrosing therapy for esophageal varices.

PMID- 15168255
TI  - Possible prevention of fulminant hepatic failure in four children with acute
      severe hepatitis.

PMID- 15168256
TI  - Is the term "ACF" necessary in humans?

PMID- 15168257
TI  - What is responsible for the development of the distinctive pattern of gastritis
      induced by Helicobacter pylori infection?

PMID- 15168258
TI  - Chemotherapy for advanced hepatocellular carcinoma: systemic chemotherapy or
      hepatic arterial infusion chemotherapy?

PMID- 15168259
TI  - Peribiliary cysts have at least two different pathogeneses.

PMID- 15168260
TI  - Hepatocellular carcinoma and NASH.

PMID- 15168261
TI  - [Barcelona Bipolar Eating Disorder Scale (BEDS): a self-administered scale for
      eating disturbances in bipolar patients].
AB  - INTRODUCTION: The presence of eating disorders in bipolar population is not rare,
      with rates over 10 %, according to the few available epidemiologic studies,
      however the literature on this issue is still scarce. An even higher percentage
      of bipolar individuals suffer from serious problems related to eating behavior
      without fulfilling criteria for DSM-IV eating disorder. METHODS: The Bipolar
      Eating Disorders Scale (BEDS) was designed on the basis of the existing eating
      scales, adjusted to the characteristics of bipolar disorders from the complaints
      of our sample of patients (n=350). Subsequently, a group of experts made the
      selection of the most representative and independent items in order to obtain a
      short, 10-item scale, aimed at assessing the intensity and frequency of eating
      dysfunctions in the bipolar population and not at diagnosis. We administered the
      scale to a healthy control group (n=55) to evaluate feasibility and to determine
      the cut-off score. RESULTS: The BEDS is a 10-item simple, self-administered
      scale. Average time of completing this scale is about 1.13 min (1 min, 21
      seconds) +/-26 seconds. Median score was 6 and the mean score was 6.6 with a
      standard deviation of 3.7, this being the reason why the cut-off point was found
      to be around 13 points. Patients receiving scores over 13 may require an
      individualized intervention to evaluate which were the main difficulties and to
      propose treatment. CONCLUSIONS: The BEDS allows for a rapid and effective
      evaluation of both the intensity and the frequency of eating dysfunctions in
      bipolar patients in order to perform an adequate intervention for the specific
      needs of each one of the patients.

PMID- 15168262
TI  - [Topiramate use as treatment in restless legs syndrome].
AB  - INTRODUCTION: Restless legs syndrome is an underdiagnosed disorder of unknown
      etiology, that generates severe sleep and life quality disturbances. In its
      therapeutic approach, drugs with very different action mechanisms and variable
      results have been used. METHODS: Nineteen outpatients diagnosed of restless legs
      syndrome were studied observationally. A semistructured interview was carried out
      and physical variables (weight, arterial pressure and heart rate), sensitive and
      motor symptoms, effective dose of topiramate, side effects and fulfillment of the
      treatment at 30, 60 and 90 days were studied. RESULTS: The patients studied, with
      an average age of 62.052 +/- 6.22 years, showed improvement in sensitive and
      motor symptoms, as well as non-significant reductions in cardiovascular
      parameters. The mean effective dose of topiramate was established at 42.1 +/-
      18.7 mg. A significant reduction in weight stands out among the side effects.
      CONCLUSIONS: Topiramate is profiled as an effective treatment in restless legs
      syndrome, with good tolerability and minimal side effects.

PMID- 15168264
TI  - [Consumption of psychodrugs. Influence of family dysfunction].
AB  - INTRODUCTION: The objective of this study is to know the prevalence of psychodrug
      consumption in Primary Health Care, related factors and influence of the family
      factor on this consumption. METHODS: Observational cross sectional study carried
      out in an urban Health Care Center. A total of 434 patients older than 14 years
      old, who are health care consumers, were included. They were selected by
      systematic sampling for 6 consecutives weeks. Psychodrugs consumption and related
      factors were measured by a questionnaire designed for this purpose. The
      questionnaire was filled out by personal interview and case history revision.
      Existence of family dysfunction was determined by self-applied Apgar-family
      questionnaire. RESULTS: Prevalence of psychodrugs consumption was 26% (95 % CI:
      22-30). A total of 53% were benzodiazepines and 27% were antidepressants (73 %
      are SSRI). There was family dysfunction in 20 % of consumers and 12 % of non
      consumers, which is a statistically significant difference (p<0.01). By logistic
      regression, being between 45-64 years old (OR: 3.18), or more than 65 years old
      (OR: 3.29), being female (OR: 2.2), being a housewife (OR: 3.07), having
      psychiatric background (OR: 15.2) and having important family dysfunction in the
      Apgar-family questionnaire (OR: 7.19) were the variables which appeared as
      associated with this consumption. CONCLUSIONS: Consumption of psychodrugs in
      Primary Health Care consumers is 26 %. Being 45 years old or more, female and
      housewife are possible factors which predict psychodrugs consumption. Psychiatric
      disease antecedents and having important family dysfunction are also associated
      independently. These should be kept in mind to improve medical prescription of
      these drugs in Primary Health Care.

PMID- 15168263
TI  - [Assessment of drug attitudes in patients with schizophrenia: psychometric
      properties of the DAI Spanish version].
AB  - INTRODUCTION: The aim of the present study was to translate into Spanish and
      evaluate interrater reliability, internal consistency, and convergent validity
      with the Insight Treatment Questionnaire (ITAQ) and Buchanan's compliance
      measure, and their relation with sociodemographic and clinical variables of the
      Spanish version of the Drug Attitudes Inventory (DAI). METHODS: The sample was
      made up of 80 patients diagnosed of schizophrenia, between 15 and 65 years old,
      of both genders, who voluntarily accepted to participate in the study and were
      informed and whose clinical conditions made the evaluation possible. Convergent
      validity with ITAQ was calculated in a subsample of 60 subjects and interrater
      reliability was evaluated in 20 cases. RESULTS: The men and all those who
      received concomitant treatment with anxiolytic and/or antidepressants obtained a
      higher score on the DAI. Interrater reliability coefficient was 0.61 (p<0.001),
      and Chronbach's alpha=0.57. Correlation between DAI and ITAQ was r=0.476, p<0.01,
      and patients with poor compliance according to Buchanan's classification obtained
      less score in DAI than those with medium and high treatment compliance.
      CONCLUSIONS: The Spanish version of the DAI demonstrated convergent validity and
      moderate reliability to evaluate treatment compliance in a Mexican sample of
      schizophrenic patients.

PMID- 15168265
TI  - [Traumatic childhood background, impulsiveness and hypothalamus-pituitary-adrenal
      axis dysfunction in eating disorders. A pilot study].
AB  - INTRODUCTION: Some studies have stressed the importance of childhood traumatic
      events in the etiology of eating disorders (ED), suggesting that the
      abnormalities in the response mechanisms to stress and in the functioning of the
      hypothalamus, pituitary-adrenal axis (HPA) could be important in the
      physiopathology of eating behavior disorders. Some preliminary findings suggest
      that some ED subtypes, as the post-traumatic stress disorder, have a
      hyperreactivity state of the HPA axis with increased sensitivity to
      dexamethasone. METHODS: A total of 25 patients diagnosed of ED according to DSM
      IV criteria, without any major depressive episode or history of bipolar or
      psychotic disorder were included. To assess the HPA axis, the dexamethasone
      suppression test was performed with 0.25 mg. The patients were administered the
      Bernstein childhood trauma questionnaire, the Green trauma history questionnaire,
      impulsiveness specific questionnaires and the SCID-II questionnaire for
      personality disorders. RESULTS: 12% had a traumatic background that did not show
      any relationship with the EBD subtype. The most impulsive patients with more
      borderline traits had a significantly greater number of traumatic backgrounds
      (p<0.005). A significant relationship was found between cortisol suppression and
      presence of traumatic history (p<0.005). The most impulsive patients with more
      borderline traits had lower post-dexamethasone cortisol plasma levels (p<0.005).
      CONCLUSIONS: Trauma in ED is associated to greater impulsiveness and presence of
      borderline personality traits that entails an HPA axis dysfunction and is
      translated into enhanced suppression of plasma cortisol.

PMID- 15168266
TI  - [Efficacy of electroconvulsive therapy: a systematic review of scientific
      evidences].
AB  - We carried out a systematic study of bibliographical review of scientific
      evidence provided by clinical trials that assessed the short, medium and long
      term efficacy of electroconvulsive therapy (ECT) from 1965 until June 2003. The
      studies with the following features have been excluded: a) those in which ECT is
      not the aim of the research; b) those that do not compare ECT with another
      different treatment; c) those in which the aim of the research is not to evaluate
      the efficacy of ECT, and d) those in which the studies are not randomized
      clinical trials. We have used the biomedical databases Medline, Psyclit, IME and
      Cochrane. On applying the corresponding search strategies on every
      bibliographical repertory, a total amount of 916 studies were found, which were
      reduced to 62 after having applied the specified exclusion criteria. The
      scientific evidence obtained, which compare the efficacy of ECT exclusively in
      depression, schizophrenia, mania and Parkinson disease, are systematized.

PMID- 15168267
TI  - [Evaluation of the effectiveness of integrated psychological therapy in long-term
      evolution of patients with schizophrenia].
AB  - INTRODUCTION: Psychosocial therapy programs have been effective in relapse
      prevention, symptoms control, and functional improvement in patients with
      schizophrenia. Accordingly, and in addition to medication, they are currently an
      indicated therapy component. Therapy efficacy of the package used in this study
      was positive in short-term follow-ups and is now appropriate to analyze them four
      years later. METHOD: Clinical and social functioning effects of a psychosocial
      intervention package, consisting of psychoeducation and integrated psychological
      therapy (IPT) with patients, and psychoeducation, behavioral therapy and problem
      solving training with families, were studied in 20 out-patients with
      schizophrenia (using pre-treatment, post-treatment and four-year follow-up
      measures). RESULTS: Within groups results indicate a sustained improvement in the
      treatment group as compared to a 15 out-patients comparison group that received
      standard treatment. All participants were on stable regimens of antipsychotic
      medications. After the follow-up period, however, between groups differences tend
      to diminish. CONCLUSIONS: The overall findings indicated that this package has
      produced encouraging effects still apparent in the 4 year follow-up. However, the
      intervention procedure merits further investigation, and suggestions are made to
      keep a low-level, long-lasting psychosocial intervention, adapted to each
      patient's needs.

PMID- 15168268
TI  - [Epileptic psychosis: a case report].
AB  - Schizophrenia and epilepsy are two disorders that sometimes concur in the same
      person. According to the present classifications for the diagnosis of mental
      disorders, these patients would receive two different diagnoses without
      contemplating the possibility that they are related disorders. However, in some
      cases, it is possible to determine a probable relationship between both disorders
      that can be expressed in both symptoms and evolution. In this text, we present a
      case of a patient with epilepsy who developed a mystic and religious delusional
      picture. According to some authors, this theme may be more frequent in patients
      with epilepsy. In addition, temporal damage is associated in epilepsy and
      psychotic disorders. In this paper, we review the possible similarity between
      both disorders. Nevertheless, the relationship between both diseases is not that
      clear and more research is needed.

PMID- 15168269
TI  - [Early onset Munchausen's syndrome].
AB  - This study presents a clinical case description of a factitious disorder in a
      woman whose diagnosis was made during her childhood. The onset of the disorder
      took place at 12 years of age and the fundamental clinical characteristics are:
      limited frequency with which the diagnosis is made in this period of life as well
      as the multiple symptoms manifested by the patient, both abdominal as well as
      neurological and hemorrhaging ones. A careful analysis of the personality traits
      and biographic history of the patient was also performed. The characteristics of
      the factitious disorder in childhood, as well as the relationship of this
      syndrome with the personality disorders, are discussed.

PMID- 15168270
TI  - [Stages of change in eating disorders: considerations about its conceptualization
      and assessment].

PMID- 15168272
TI  - [Basics foundation and results of the vacuum therapy in the reconstructive
      surgery].
AB  - Vacuum therapy (vacuum assisted wound closure (V.A.C.(R)) is a non invasive
      method to promote wound healing. It is based on defined, controlled negative
      pressure application via medical-grade reticulated polyurethane ether or
      polyvinyl foam dressing to wound surfaces. The technique is characterized by
      continuous removal of wound exudates and hence reduction of extravascular,
      interstitial fluid, subsequently leading to enhanced microcirculation.
      Experimental studies revealed a positive influence both on local microcirculation
      and on granulation tissue formation. Local mechanical physical factors, yet not
      completely understood, similar to tissue expansion, apply to the wound surface
      and seem to promote cell growth. In our own patients the vacuum technique has
      been used to pretreat chronic wounds in 139 patients, to fix split thickness skin
      grafts in 148 patients and to prefabricate or delay free or pedicled flaps in 11
      patients so far. Thorough surgical debridement remains the mainstay of wound
      care. Vacuum therapy however, as an adjunctive procedure, offers significant
      advantages compared to conventional wound care methods, which call for further
      clinical and experimental studies to elucidate the basic mechanisms.

PMID- 15168273
TI  - [Scientific background of the vacuum closure - an abstract].

PMID- 15168274
TI  - Consensus of the German and Austrian Societies for Wound Healing and Wound
      Management on vacuum closure and the V.A.C. treatment unit.
AB  - Within the framework of the Three-Country Congress on V.A.C. Treatment (Vacuum
      Assisted Closure Treatment) held on May 16/17, 2003 in Salzburg, a Consensus
      Conference involving members of the Committees of the German and Austrian
      Societies for Wound Management was convened. In view of the divergence of opinion
      on the effectiveness of the treatment among the cost carriers, it appeared
      appropriate for the two Societies for Wound Healing in Germany and Austria to
      arrive at a consensus on the importance of and the indications for the management
      of wounds with the vacuum closure method. Since the first clinical applications
      in the nineteen-forties, both the indication spectrum and the number of
      applications have increased continually. In addition to diverse vacuum closure
      systems, there is patented computer-controlled system technology available that
      is established V.A.C. treatment. Although this is a hospital-based system, it can
      also be used on an outpatient basis by appropriately trained physicians and
      nursing staff and in instructed patients. For some indications, vacuum closure
      and V.A.C. management is considered the treatment of choice, since no equivalent
      alternative methods are available. A con-benefit analysis shows that vacuum
      closure and V.A.C. treatment is cost effective.

PMID- 15168275
TI  - [The use of v.a.C.-system in wound management for borderline indications].
AB  - Vacuum sealing has increasingly become established as a method adapted to treat
      acute and chronic wounds. Temporary sealing of the open abdomen represents an
      alternative therapeutic approach. The principle of inverse tissue expansion
      prevents ventral herniae from developing in the course of delayed abdominal-wall
      closure. In patients undergoing vascular surgery, the method can be uneventfully
      adopted in treating chronic ulcer following revascularisation. The accelerated
      healing process, while reducing the duration of therapy, turns out to be cost
      efficient.

PMID- 15168276
TI  - [New application of v.a.C. (vacuum assisted closure) in the abdominal cavity in
      case of open abdomen therapy].
AB  - OBJECTIVE: The problem of the temporary vacuum assisted closure (V.A.C.) of open
      abdomen situation is that the fluids, following the negative pressure, pass the
      abdominal cavity and in case of a local infection disseminate over the whole
      abdominal cavity. METHODS: The usual open abdominal wound V.A.C. technique was
      modified by using an auxiliary, independently operating V.A.C. system positioned
      intra-abdominally and connected with a separate drainage tube introduced into the
      lateral abdominal wall. This arrangement prevents further spreading of a local
      intra-abdominal infection in case of a necrotising pancreatitis after traumatic
      pancreas rupture. RESULTS: The drainage volumes were comparable from superficial
      and intra-abdominal V.A.C. system. A total of 30 reoperations were necessary due
      to a leasion of the pancreas before a primary closure of the open abdominal wound
      could be applied after 72 days. No bowel fistulas or intra-abdominal abscess
      formations were observed. The follow-up have not shown any hernia of the
      abdominal wall up to the present. CONCLUSION: Additional intra-abdominally
      positioned V.A.C. system with an own drainage system supports open abdomen
      therapy with the standard abdominal V.A.C. system and prevents dissemination of
      intra-abdominal infection.

PMID- 15168277
TI  - ["Abdominal dressing" - a new method of treatment for open abdomen following
      secondary peritonitis].
AB  - INTRODUCTION: Treatment of open abdomen following secondary peritonitis is a
      challenge for surgery and intensive care units (ICU). The aim of this study was
      to compare three different concurrent treatment strategies. METHODS: Patients
      suffering an open abdomen following surgery for secondary peritonitis at the
      Department of General Surgery from 01/01 to 12/03 were investigated. Factor
      studied: duration of open abdomen, incidence of multi-organ failure, need for
      surgical revisions, length of stay (LOS) in ICU, nursing requirements (change of
      dressing/day), survival and integrity of abdominal wall after discharge.
      Treatment strategies included: open packing (OP), classic vacuum assisted
      (V.A.C.(R))-therapy with silicone net protection for the intestine (CV) and
      V.A.C.(R)-therapy with "abdominal dressing" a newly developed meshed polyvinyl
      wrap (AD). RESULTS: 21 patients were studied: 5 patients were treated with OP, 8
      patients with CV and 8 patients with AD. Mean LOS was 65 (OP) vs. 53 (CV) vs. 42
      (AD) days (NS), peritonitis related death was 3 (OP) vs. 1 (CV) vs. 0 (AD) (p <
      0.05 Chisquare test). Median nursing effort was 4 dressings/day (OP), 0.5 (CV)
      and 0.5 (AD) (p < 0.005 OP vs CV, AD Kruskal-Wallis test). CONCLUSION: The
      "abdominal dressing"-therapy seems to be a more efficient treatment option in
      patients suffering from open abdomen following secondary peritonitis. A trend
      towards shorter ICU-LOS, lower mortality rates and reduced nursing requirements
      support our hypothesis.

PMID- 15168278
TI  - [Experiences with the v.a.C. therapy in surgery - proceedings and limits].

PMID- 15168279
TI  - [V.a.C.-therapy in abdominal surgery - experiences, limits and indications].
AB  - Compared to other surgical disciplines the significance of V.A.C.-therapy is
      rarely noticed in abdominal surgery. This may be due to uncertainty in defining
      clear indications or lack of technical know-how. METHODS: We report on five
      selected septic cases in abdominal surgery without clearly defined indications
      for V.A.C.-therapy (ischiorectal abscess, perforation in Crohn's disease, pelvic
      abscess due to perforation caused by rectal carcinoma, abdominal compartment
      syndrome, anastomotic leak after rectal resection). RESULTS: Regarding the
      individual aspects of indication, V.A.C.-therapy could be used successfully in
      the demonstrated cases. Under the palliative aspect, V.A.C.-therapy on a
      malignant wound bed allowed an early treatment with chemotherapy. DISCUSSION:
      According to the literature dealing with V.A.C.-therapy, enterocutaneous
      fistulas, exposed viscera, enteral surfaces as well as malignancy in the wound
      bed are considered to be contraindications for the method. Reffering to our
      observations, these diagnoses should not be strictly regarded as
      contraindications. Elaboration of clear guidelines that point out clearly defined
      indications for V.A.C.-therapy should be the goal for the future.

PMID- 15168280
TI  - [Vacuum assisted closure therapy improves early postoperative lung function in
      patients with large sternal wounds].
AB  - Vacuum assisted closure of sternal wounds is a sound strategy for patients with
      severe poststernotomy mediastinitis and sternal bone necrosis. As a bridging
      therapy to reconstructive surgery it provides an adequate temporary stabilization
      of the thorax. It enhances lung function and reduces pulmonary complications.

PMID- 15168281
TI  - [Early treatment of sternal wound infections with vacuum assisted closure therapy
      reduces involvement of the mediastinum and further diminishes the need of plastic
      reconstructive surgery].

PMID- 15168282
TI  - [Ulcus shaving and v.a.C.(R) therapy].
AB  - The therapy of venous ulcerations takes a lot of time, material and personal as
      well as its characterized with a high rate of recurrences. The surgery of the
      underlying varicoses is not adequate appreciated under DRG conditions. To avoid
      case splittings and also unnecessary hospital stays, with the described treatment
      process: saphenectomy, dissection of perforans veins, ulcer shaving, mesh graft
      with vacuum therapy, all in one session, a complex, economical and patient
      friendly therapy regime with a low rate of recurrences is available.

PMID- 15168283
TI  - [Care aspects in v.a.C. therapy].

PMID- 15168284
TI  - [Occlusion therapy of v.a.C. in multimodal concepts of soft tissue defects].

PMID- 15168285
TI  - [Experiences with v.a.c. therapy, fluorescein vital dye and Integra in large
      surface avulsion injury of both legs].

PMID- 15168286
TI  - [Closed subfascial v.a.C.-therapy in periprosthetic hip infections].
AB  - Infections after hip arthroplasty can lead to protracted and complicated
      treatments. A great problem is thereby the persistant secretion after surgical
      revision. 8 patients (3 x after acetabulum cup replacement, 2 x after Girdlestone
      hip, 2 x after spacer implantation and one case of rearthroplasty) have been
      treated with a V.A.C.-therapy after bacterial infection and persistant wound
      secretion. In all cases a pathogen organism could be identified during the
      frustrated attempts of sanitation. After meticulous debridement and jet lavage in
      each case, 1-3 polyvinyl sponges have been placed either periprosthetic or in the
      resection cavity with a transcutan tube outgoing. The wounds have been closed in
      layers. Initially a pressure of 200 mm Hg via V.A.C. has been attached. After 48
      72 h an alteration from haemorrhagic to serous secret could be observed and
      afterwards the pressure has been reduced to 150 mm Hg. After a mean period of 11
      days (8-13) the infection parameters have been retrogressive, the wound secretion
      was obviously reduced and the sponges were removed. During the remaining
      hospitalization of each patient no complications occured. In the mean follow-up
      of 21 months (2-46) no reinfections have been observed. Although the V.A.C.
      therapy does not count to the primary therapy concepts of periprosthetic hip
      infections, it stands for an effective therapy option in exclusive cases.

PMID- 15168287
TI  - [Intraoral application of vacuum-assisted closure in the treatment of an extended
      mandibular keratocyst].
AB  - In extended cysts of the jaw bone particular demands are made in terms of wound
      closure, especially if an intraoral surgical approach is chosen. A tight closure
      is even more important if the bony defect has been filled with an alloplastic
      material or autologous cancellous bone. In our case a keratocyst of the left
      mandibular angle and ascending ramus was treated. After enucleation of the cyst
      and grafting with autologous cancellous bone the graft was lost following a wound
      breakdown. Subsequently a system was developed to apply intraoral V.A.C.-therapy.
      This led to a safe separation of the cystic defect and the oral cavity and a
      conditioning of the wound ground. A grafting with an alloplastic material was
      carried out successfully. With this method the length of treatment could be
      reduced by several months compared to a conventional therapy with an obturator.

PMID- 15168288
TI  - [Treatment of soft tissue defects on hand and forearm with vacuum assisted
      closure].

PMID- 15168289
TI  - [Results of vacuum therapy (v.a.C.) of superficial and deep dermal burns].
AB  - BASIS: This prospective multi-centre study in co-operation with the Wake Forrest
      University covered the area of applications for treatment of fresh, superficial
      and deep dermal burns and scalds (grade II a-b). The micro-circulation
      relationships, wound healing time, extent of germ settlement and the connective
      tissue edema were of particular interest (together with the increase or decrease
      in burn depth). Moreover, the economical aspects were compared with conservative
      therapy. MATERIAL AND METHODS: his study was carried out on our intensive care
      ward on 11 patients suffering from burn injuries and we took the healing process
      as the basis (2001-2003). Inclusion criteria for the study were burns on both
      hands, degree II a-b, occurring trauma less than 6 hours ago and a treatment
      period of minimum 48 hours. In any case the hands inflicted with deeper and
      extensive burns (assessment by 2 experienced, independent appraising plastic
      surgeons) were subject to V.A.C. therapy. The standard conventional, conservative
      therapy applied to the other hand was taken for comparison or control purposes to
      determine the success. Since October 2001 we use the IC-View perfusography with
      ICG colouring (ICG pulsion, PULSION Medical Systems AG, Munich, Germany) for
      objective findings both previously and during the course of treatment. A
      respective quantitative analysis and assessment of the recorded video sequences
      were made with the help of special software (IC-CALC, PULSION Medical Systems AG,
      Munich, Germany). Here too, the intensity of the fluorescence indicated the blood
      circulation through the connective tissue and is on the same level. Basis for
      this method of study was the work of Holm et al. in our department. RESULTS:
      Above all, the results of our study revealed a significant reduction or
      prophylaxis of the connective tissue edema. Due to improvement in the micro
      circulation, also supported by dynamic IC-View laser-fluorescence videography it
      could be determined that the wound healing process was quicker and without
      complication in the majority of cases. This was all the more true, although even
      when the extent of the deep dermal hand burns treated by V.A.C. therapy was
      greater than on the hand taken for comparison. Extending the therapy applied to
      the hand to the entire extremity could contribute to avoiding operative stress
      (escharotomy) in selected cases. Troublesome supporting of the hands and the
      ergotherapeutic use of splints were not necessary because of the exact fixation
      of the extremities ensured by the vacuum method. The advantage became more
      obvious when both the cost factor and time expenditure were considered and
      compared with previous conservative therapy. CONCLUSIONS: In the near future the
      treatment of superficial and deep dermal burns/scalds by V.A.C. therapy can help
      in reducing the expenditure in time, material and personnel when treating large
      area wounds. A further advantage is not only to be seen in the optimised healing
      process in the case of superficial and deep dermal burn wounds but also in the
      reduction or even avoidance of extensive escharotomy with the accompanying
      operation trauma. In this respect close mesh control of the blood circulating
      conditions appeared to us to be important and as a result of our study V.A.C.
      therapy was approved in December 2002 for the treatment of superficial and deep
      dermal burns by FDA (Dept. of Health and Human Services).

PMID- 15168290
TI  - [The use of subatmospheric pressure to prevent burn wound progression: first
      experiences in burn wound treatment].
AB  - Thermal injury applied to living tissue results in zones of injury. Cell death is
      complete in the zone of coagulation. Beneath this area, there is the zone of
      lesser injury, where most of the cells are initially viable. If this zone of
      stasis is not reversed, the burn wound will progress. One of the major aspects to
      prevent progression is to reduce the edema formation and to preserve
      microcirculation. We present our first experiences to prevent the progression by
      use of topical negative pressure. Within the last months, all patients with
      bilateral partial thickness hand burns were included into this treatment
      protocol. Within one patient, one hand was treated with the V.A.C. (KCI,
      Austria), the contra lateral one by use of Flammazine (Smith and Nephew,
      Germany). Our first observations and data indicate, that both important factors
      (edema and microcirculation) could be influenced positively by use of the V.A.C.

PMID- 15168291
TI  - [Design and prospects of modern wound treatment with the techniques of vacuum
      closure].

PMID- 15168292
TI  - [Vacuum-assisted Therapy in Vascular Surgery].
AB  - Since the first use of vacuum-assisted therapy (V.A.C.) in wound care, the
      indications of this therapy have rapidly expanded. Vascular surgery presents many
      types of problematic wounds. In the current cost conscious atmosphere, there is a
      great demand for simple and effective therapies. The V.A.C. system has a lot of
      potential in the management of vascular wounds. In this article we present
      indications for vacuum-assisted therapy in vascular surgery: chronic leg ulcers,
      mesh skin graft, wound care after fasciotomy for compartment syndrome,
      problematic inguinal wound, false aneurysms, diabetic foot gangrene and
      amputations with marginal circulations.

PMID- 15168294
TI  - [Indications and results of v.a.C therapy treatments in vascular surgery - state
      of the art in the treatment of chronic wounds].
AB  - Almost 10 % of the population are concerned in the course of her life by chronic
      wounds, mortality resulting from this amount to 2.5 %. The Vacuum assisted
      closure (V.A.C.) therapy represents a modern procedure for the treatment of
      chronic wounds. Also in some first appearing offering no prospects cases hereby
      the Major amputation can be prevented and the majority of chronic therapy
      resistant wounds can be healed. Due to first experiences with the V.A.C. therapy
      with the treatment of infected vascular grafts in the stage II and III after
      Szilagyi it also offers a success - promising option to concern the extremity and
      the life of the patient and to receive but also the infected graft in situ.

PMID- 15168293
TI  - [Wound treatment throughout time].

PMID- 15168295
TI  - [V.A.C.-therapy and laser-induced fluorescence of indocyanine-green (IC-view), an
      assessment of wound perfusion in diabetic foot syndrome].
AB  - Aim of the study was the use of IC-View for monitoring the effect of V.A.C.(R)
      therapy on perfusion in diabetic wounds and the surrounding skin. We present data
      of ten patients with diabetic foot syndrome. Seven men and three women with age
      from 56 to 86 (mean 68) years were treated with V.A.C.(R)-therapy for 7 to 24
      (mean 12) days. The perfusion index was calculated for the wound itself and for
      the surrounding skin before and at the end of V.A.C.(R)-therapy. The perfusion of
      the wound showed an increase under V.A.C.(R)-therapy of 31 % (6-62.5 %). The
      perfusion index calculated for the skin around the defect achieved an increase of
      14 % (1.5-38 %). All defects were covered with meshed skin graft.

PMID- 15168296
TI  - [Use of vacuum therapy during defect coverage of the upper extremity with
      microsurgically grafted arterialized venous flaps].
AB  - Arterialized venous soft tissue flaps are defined as tissue portions usually
      harvested from the anterior and distal third of the forearm over a venous pathway
      to be transplanted to another recipient area. Basically, they are composed of
      skin, subcutaneous tissue, and subdermal venous plexus. At the recipient site
      flaps are perfused by a nourishing artery while the other veins are connected to
      one or more regional veins. The retrograde blood perfusion often results in
      edema, temporary epidermolysis, or even some degree of skin necrosis that
      disappear during subsequent treatment. To circumvent these drawbacks grafting of
      arterialized flaps was combined with local application of vacuum to overcome the
      venous initial stasis, resulting in improved healing and survival of these flaps.

PMID- 15168297
TI  - [Management with v.a.C. in phlegmonous tissue defects of the abdominal wall after
      abdominoplasty].
AB  - Infected defects with tissue defects of the abdomial wall after abdomioplasty are
      a severe complication. Management of these progessive infections involves
      multiple step surgery. V.A.C.-therapy could be an alternative to open wound
      treatment.

PMID- 15168298
TI  - [The case of a patient with multiple superinfected necrosis of both legs caused
      by vasculitis disease].
AB  - Vasculitis can lead to skin necrosis, which typically shows decayed recovery
      tendency and is able to lead to local as well as systemic inflammation. By
      repeated necrosectomy, vacuum therapy, split skin graft transplantation as well
      as simultaneous immunosuppression and systemic antibiotics, the cutaneous
      manifestations of vasculitis where cured.

PMID- 15168299
TI  - [Several aspects of foam materials and their possible interactions with the wound
      surface in the vacuum therapy].
AB  - Tissue engineering research has demonstrated the potential of a variety of
      different matrix materials to enable cell adhesion, diffusion of nutrients,
      vascular ingrowth, nutrition and growth promotion. Therefore it appears
      attractive to apply these features also to topical negative pressure therapy. The
      article discusses several aspects of foam materials and their possible
      interactions with the wound surface.

PMID- 15168300
TI  - [Pressure conditions under VVS-foams - an experimental in-vitro- and in-vivo
      analysis].
AB  - The aim of this study was to determine the pressure conditions in the tissue
      beneath and on the surface of wounds. This was done in vitro both on a plain
      surface and on a bovine muscle. In comparison we measured the pressure of the
      anterior tibial muscle of a patient with compartment syndrome. Besides, we
      applied negative pressure using just one drape connector and measured the
      pressure in different distances to look if the pressure is constant in large
      V.A.C.(R) dressings. Both polyurethane and polyvinyl alcohol foams were used.

PMID- 15168301
TI  - [The V.A.C. system (vacuum assisted closure) as bridging between primary
      osteosynthesis in conjunction with functional reconstructed of soft tissue--open
      fractures type 2 and type 3].
AB  - Open fractures are complex injuries affecting the integrity of bones and adjacent
      soft tissue. The therapeutic goals in dealing with open fractures should consist
      of primary osteosynthesis in conjunction with functional reconstruction of soft
      tissue. In a period over 2 years, 26 patients were treated with extensive trauma
      in an interdisciplinary approach. These patients suffered from open fractures
      type 2 and 3. All patients were treated by primary osteosynthesis, and temporary
      wound closure with V.A.C.-system. Definitive wound closure was achieved by day 31
      after injury. In contrast to a review of the pertinent literature we report the
      successful free tissue transfer in 21 patients during the critical period between
      72 hours and several months preceded by the use of V.A.C.-system for the
      temporary coverage of open wounds.

PMID- 15168302
TI  - [Vacuum therapy in a pre- and postsurgical ulcera crurum].
AB  - Chronic wounds are often a diagnostic as well as a therapeutic problem. Three
      case reports depi important differential diagnoses. The importance and efficacy
      of vacuum assisted closure in a presurgical treatment as well as after mesh graft
      transplanation will be described.

PMID- 15168303
TI  - [The treatment of heel pressure ulcer with V.A.C. therapy using the new V.A.C.
      GranuFoam "Heel-Dressing"].
AB  - The treatment of heel pressure ulcer represents one od the difficulties in
      treatment of pressure ulcer, because of its pressure load conditional on the
      calcaneus, the missing of muscle buffer and the huge number of tender insertions.
      With the V.A.C.-Therapy based upon interdisciplinary pretreatment (debridement,
      control of infection, circulation and metabolism and pressure relief) the growth
      of granulation tissure succeeds in a very fast time. The new V.A.C.-GranuFoam
      Heel Dressing contains the possibility to apply the V.A.C.-Therapy safe and very
      quick, in spite of the difficult ulcer location at the heel. Moreover it includes
      the necessary transfer of the T.R.A.C-Pad on the top of the foot to prevent new
      increase of pressure.

PMID- 15168304
TI  - [Vacuum assisted wound closure after excision of a high risk melanoma heel wound 
      using the v.a.C. heel-dressing].
AB  - Vacuum-assisted wound closure is established in acute wound treatment and assists
      granulation tissue as well as promotion of graft survival in critical
      localisation. A new vacuum-assisted wound closure device is launched for the
      treatment of heel wounds (V.A.C. GranuFoam Heel Dressing). First experience with
      this heel contour shaped dressing is presented in a case of primary surgical care
      of a high risk melanoma. The initial defect after excision, measuring 8 x 6 x 3.5
      cm, granulated by V.A.C. treatment in 5 weeks to skin surface niveau and was
      successfully covered with a full thickness skin graft. The V.A.C. Heel Dressing
      is easy to apply, reduces vacuum leakage und increases patients' comfort and
      treatment safety in comparison to "classic" vacuum dressings.

PMID- 15168306
TI  - [The treatment of heel pressure ulcer with the vacuum therapy (v.a.C. system)].

PMID- 15168305
TI  - [Influence of foam- and tubing material of the vacuum assisted closure device
      (v.a.C.) on the concentration of transforming growth factor Beta 1 in wound
      fluid].
AB  - BACKGROUND AND PURPOSE: The Vacuum Assisted Closure device (V.A.C.) is commonly
      used for the treatment of problematic wounds. Furthermore, wound fluid can be
      easily collected with this device for research purposes. However, there is
      inadequate information as to whether the measurement of biomoieties of importance
      to wound healing is affected by the exposure of wound fluid to V.A.C. components,
      namely Polyurethane-foam and tubing. This study is an attempt to evaluate whether
      exposure of wound fluid to either V.A.C.-components affects concentrations of
      transforming growth factor beta 1 (TGF-b1) in wound fluid. MATERIAL AND METHOD:
      Wound fluid was gathered from five decubital ulcer patients using the foil
      technique and was exposed to sterile pieces of the V.A.C. Polyurethane-foam,
      tubing material or nothing for zero, one or five hours. Saline served as control.
      The concentration of TGF-b1 was measured using sandwich-ELISA. The resulting data
      were analyzed using two-way ANOVA, Newman-Keuls and Bonferroni t-Test. RESULTS:
      The concentration of TGF-b1 decreased significant in all three groups during the
      five hours of the experiment (p < 0.05). There was no significant decrease in TGF
      b1 concentration at any time point in-between the groups. CONCLUSION: From this
      study, we conclude that wound-fluid collected from the V.A.C.-device via the
      polyurethane-foam or tubing for purposes of analyzing concentrations of TGF-beta
      1 should not be different from fluid collected using the foil technique.

PMID- 15168307
TI  - [V.A.C. therapy in diabetic gangrene of the right mid- and forefoot].

PMID- 15168309
TI  - [Economical use and transfer management of v.a.C. therapy as an example].
AB  - There are many outspoken questions in the sector of attendance of wounds. So this
      fact is accompanied by scepticism mostly in the ambulant field. The missing
      knowledge applicating a certain skill/technique and the special first aid are
      deterring practising people as well as specialists here in Germany. The aspect
      and advantage of political economy resulting of this reduced medical treatment
      was not respected and left out of consideration.

PMID- 15168308
TI  - [V.a.C.(R) therapy: economic issues of the health care market].

PMID- 15168310
TI  - [Indication and clinical results of buried skin grafting to treat problematic
      wounds].
AB  - In 1920 Braun described a technique of skin grafting particularly designed for
      areas where shearing forces, high pressure and extensive secretion cause
      repetitive loss of conventionally transplanted skin. During the last 10 years we
      successfully used this technique when impaired wound healing was encountered due
      to various reasons. Clinical examples of application and results are presented.
      By combining this technique with vacuum therapy, formation of granulation tissue
      can be accelerated, thereby resulting in successful transplantation of
      problematic and therapy resistant wounds.

PMID- 15168311
TI  - [Salvage of exposed alloplastic materials in irradiated wounds - a case report].
AB  - BACKGROUND: Modern multimodal concepts of complex reconstructions and advanced
      wound management enlarge strategies for surgical oncological therapies. One of
      the mainstays of classical surgical therapy in case of exposed alloplastic
      materials in irradiated wounds was to remove the foreign body due to the risk of
      infection. This loss of integrity and function of the contaminated host bed was
      to allow wound healing and closure. METHOD: We report the management of a 56-year
      old female patient who developed a lyomyosarcoma at her left shoulder girdle 8
      years after radiation of the left thorax because of breast cancer. After radical
      tumor resection and exarticulation of her left arm in the shoulder joint a
      necrosis of the soft tissue envelope developed, leading to an exposed alloplastic
      mesh. Staged debridement and continuous application of negative pressure was
      performed three times. Ultimate plastic coverage was performed by means of a
      pectoralis myocutaneous island flap from the other breast. RESULTS: After staged
      debridement and repeated vacuum application excellent wound cleaning,
      neovascularisation, wound contraction and formation of granulation tissue within
      the previously irradiated tissue zone was observed. Until fourteen months
      postoperative wound coverage remained stable and no signs of infection were
      observed. DISCUSSION: By means of negative pressure therapy even in radiated
      wounds excellent wound cleaning and sufficient formation of granulation tissue
      can be achieved. In some cases negative pressure therapy together with staged
      debridement allows reintegration of exposed and therefore potentially
      contaminated alloplastic meshes into new formed granulation tissue in radiated
      wounds respectively radiation ulcers. Thus leading to the possibility of ultimate
      plastic coverage.

PMID- 15168313
TI  - [Revitalization of a gluteal abscesses with v.a.C. therapy (vacuum assisted
      closure)].
AB  - Abscess formation is a frequent complication following gluteal injection. Septic
      abscesses as well as aseptic necrosis of muscle or subcutaneous adipose tissue
      require surgical management. We present a case of subcutaneous necrosis following
      gluteal injection in which vacuum-assisted closure (V.A.C. therapy) has been
      effectively applied in the phase of secondary wound healing following surgical
      drainage. V.A.C. therapy offers ambulatory management with optimal hygiene and
      patient's comfort.

PMID- 15168312
TI  - [Vacuum assisted would closure technique in bronchial stump dehiscence after
      lobectomy--a case report from thoracic surgery].

PMID- 15168314
TI  - [The impact of the VAC-treatment for locally advanced malignancy of the scalp].
AB  - Locally advanced cutaneous malignancy of the scalp is a disease that requires an
      aggressive approach to resection and reconstruction. In cases where the
      pericranium is intact a split-thickness skin graft is a simple treatment, since
      direct closure often fails because due to the lack of elasticity of the scalp. If
      there is a loss of periosteum or a skull defect local or free flaps are necessary
      for sufficient coverage. Increasing geriatric and polymorbid patients with
      impaired wound healing require surgical treatment, considering pros and cons for
      general anaesthesia. A simple method of both, combining radicality of tumor
      resection with outer table bone and skin grafting as a two stage procedure, while
      minimizing perioperative risk using local anaesthesia and analgo-sedation, using
      the vacuum assisted closure device, is presented.

PMID- 15168315
TI  - Tetanus in pregnancy.
AB  - Tetanus remains a leading cause of maternal and neonatal morbidity and mortality
      in developing countries. It is caused by the release of two toxins produced by
      Clostridium tetani, a noninvasive gram-positive anaerobic bacillus. Tetanospasmin
      is taken up by the neuronal end plates and prevents neurotransmitter release at
      the synaptic junction. This leads to spasms and is irreversible. Recovery
      requires the formation of new neurons and may take months. Generalized muscle
      spasm, respiratory compromise, and autonomic dysfunction are all common clinical
      manifestations. Diagnosis is based mainly on history and clinical examination.
      The management of the pregnant woman is similar to the nonpregnant individual.
      The main objectives are prompt prevention of further toxin absorption, wound
      debridement, antibiotic therapy, and aggressive supportive care. Primary and
      secondary prevention protocols are important worldwide because tetanus is a
      preventable disease. The tetanus toxoid vaccine can be given in pregnancy.

PMID- 15168316
TI  - Contemporary management of preterm premature rupture of membranes: determinants
      of latency and neonatal outcome.
AB  - Preterm premature rupture of membranes (PPROM) is responsible for 30% of neonatal
      morbidity and mortality in premature gestations. We sought to evaluate pregnancy
      outcomes in PPROM managed uniformly with antibiotics and steroids, and to
      determine what maternal factors influence latency. This was a retrospective
      analysis of 134 patients at 24 to 31.9 weeks with PPROM. Associations of maternal
      and pregnancy characteristics with latency were evaluated by chi-square for
      linear trend, nonparametric tests, or multivariable linear regression, as
      appropriate. Forty-three of 134 women (32%) had latencies greater than a week.
      Gestational age ( p < 0.001), admission white blood cell count ( p = 0.001), and
      amniotic fluid index ( p = 0.02) were independently predictive of latency.
      Histopathologic funisitis increased with pregnancy length. There were no fetal
      deaths or significant intraventricular hemorrhage past 28 weeks.

PMID- 15168317
TI  - Indomethacin therapy for patent ductus arteriosus in premature infants: efficacy
      of a dosing strategy based on a second-dose peak plasma indomethacin level and
      estimated plasma indomethacin levels.
AB  - The objective of this study was to determine the rate of patent ductus arteriosus
      (PDA) closure in premature infants using an adjustable indomethacin (INDO) dosing
      strategy, based on a second-dose peak plasma INDO level. We conducted a
      retrospective review of the medical records of premature infants that were
      treated with INDO for a PDA, had a second dose peak plasma NDO levels, and
      followed predetermined guidelines for INDO dosing adjustments, over a 4-year
      period (1995 to 1998). Of 103 infants treated with the adjustable INDO dosing
      strategy, 66 (64%) achieved PDA closure whereas 37 (36%) did not. No differences
      in the second-dose peak plasma INDO levels (830 +/- 339 versus 702 +/- 381
      ng/mL), day of life treatment was started (4 +/- 3 versus 4 +/- 2 days), or the
      number of doses of INDO received (4 +/- 1 versus 5 +/- 2 dose) were observed
      between responders and nonresponders. However, fourth-dose peak plasma INDO
      levels, which were available from 38 of 66 (57%) of the responders and 20 of 37
      (54%) of the nonresponders, were lower in nonresponders (1553 +/- 413 versus 1829
      +/- 609 ng/mL, p < 0.05). Patient demographics, including birth weight and
      gestational age, were similar between these groups. Using an adjustable INDO
      dosing strategy, based on a second-dose peak plasma INDO level and estimated
      plasma levels, PDA closure rates of 64% can be achieved. Although a clear
      relationship between INDO plasma levels and PDA closure was evident form this
      study, the rate of PDA closure in our study was lower than has been observed in
      studies with serial plasma INDO level monitoring.

PMID- 15168318
TI  - Infants with congenital anomalies admitted to neonatal intensive care units.
AB  - The objective of this study was to describe the congenital anomalies in 17
      Canadian neonatal intensive care units (NICUs) and their impact on mortality,
      morbidity, and resource utilization. This study was performed using a database
      analysis of 19,507 consecutive admissions. Results show that 13.7% of admissions
      had one or more anomalies. There was wide variation in incidence between NICUs
      (4.4 to 36.6%). Congenital anomalies were associated with increased severity of
      illness, and higher mortality, morbidity, and resource use. Inclusion of
      congenital anomalies improves mortality prediction in regression analyses models.
      Congenital anomalies have a significant impact on NICU outcomes and resource use.

PMID- 15168319
TI  - Oxidative and inflammatory parameters in respiratory distress syndrome of preterm
      newborns: beneficial effects of melatonin.
AB  - Reactive oxygen species play an important role in the pathogenesis of respiratory
      distress syndrome and its complications. This study was conducted to determine if
      treatment with the antioxidant melatonin would influence interleukin-6,
      interleukin-8, tumor necrosis factor alpha, and nitrite/nitrate levels in
      newborns with grade III or IV respiratory distress syndrome (radiographically
      confirmed) diagnosed within the first 6 hours of life. Prior to treatment, a
      blood sample was collected from the umbilical cord or a peripheral vein of each
      newborn. Second, third, and fourth blood samples were collected at 24 hours, 72
      hours, and 7 days, respectively, after beginning treatment with melatonin or
      placebo. Compared with the melatonin-treated respiratory distress syndrome
      newborns, in the untreated infants the concentrations of interleukin-6,
      interleukin-8, and tumor necrosis factor alpha were significantly higher at 24
      hours, 72 hours, and at 7 days after onset of the study. in addition,
      nitrite/nitrate levels at all time points were higher in the untreated
      respiratory distress syndrome newborns than in the melatonin-treated babies.
      Following melatonin administration, nitrite/nitrate levels decreased
      significantly, whereas they remained high and increased further in the
      respiratory distress syndrome infants not given melatonin.

PMID- 15168320
TI  - Uterine rupture in patients with a prior cesarean delivery: the impact of
      cervical ripening.
AB  - The purpose of this study was to examine factors that were associated with
      uterine rupture in patients attempting vaginal birth after cesarean delivery. We
      analyzed the results of all patients attempting vaginal birth after cesarean
      delivery between September 1996 to December 1999 at a single institution using a
      contemporaneously maintained registry. Maternal factors, fetal factors, and
      management of labor were all assessed to determine the risk factors associated
      with symptomatic uterine rupture at the time of attempted vaginal birth after
      cesarean delivery. Twenty-eight symptomatic ruptures were identified in 972
      attempts of vaginal birth after cesarean delivery at a gestational age greater
      than 24 weeks (2.88%). The use of preinduction cervical ripening was
      significantly associated with an increased risk of symptomatic uterine rupture
      (odds ratio, 3.92; 95% confidence interval, 1.78 to 8.62). Patients who underwent
      preinduction cervical ripening were significantly less likely to delivery
      vaginally than women who had not (46.71 versus 76.87%; p < 0.001). No other
      differences were noted between the two groups. Preinduction cervical ripening is
      associated with an increased risk of uterine rupture in women attempting vaginal
      birth after cesarean delivery.

PMID- 15168321
TI  - Complete abortion of a nonviable cervical pregnancy following methotrexate
      treatment.
AB  - Cervical pregnancy is an uncommon ectopic pregnancy that accounts for
      approximately <1% of extrauterine gestations. This condition is associated with
      an extremely high risk of massive hemorrhage and previously often required
      hysterectomy. Current early ultrasonographic diagnosis and medical management in
      conjunction with other conservative measures, which include uterine artery
      embolization and intracervical balloon tamponade, have enabled conservation of
      the uterus. A young nulliparous patient ultrasonographically diagnosed with a
      cervical pregnancy and early fetal demise at 11 and 4/7 weeks gestation was
      managed with high-dose methotrexate and folinic acid rescue treatment. On the
      second day after treatment was initiated she spontaneously passed an intact
      gestational sac accompanied by minimal hemorrhage. Treatment was continued, with
      decreasing serum beta subunit of human chorionic gonadotropin levels and
      subsiding hemorrhage. Subsequent surgical measures were not required. This case
      suggests that complete abortion of a cervical pregnancy not necessitating
      surgical measures can occur.

PMID- 15168322
TI  - Risk factors for term or near-term fetal growth restriction in the absence of
      maternal complications.
AB  - The objective of this study was to examine risk factors for term or near-term
      fetal growth restriction (FGR) in the absence of pregnancy complications. We
      completed a survey of uncomplicated single live births delivered in Greater
      Beirut, Lebanon. FGR cases were defined as below the 10th percentile of expected
      weight at gestational age. Multivariate logistic regression was used to estimate
      odds ratios (OR) and 95% confidence intervals (CIs). Main predictors of FGR were
      female gender (OR, 1.94; 95% CI, 1.46 to 2.59), nulliparity (Or, 1.66; 95% CI,
      1.25 ton 2.20), low prepregnancy weight (OR, 2.52; 95% CI, 1.58 to 4.01), short
      stature (OR, 2.59; 95% CI, 1.57 to 4.28), and low pregnancy weight gain (OR,
      1.75; 95% CI, 1.21 to 2.55). Anthropometric characteristics of mothers are
      important modifiable determinants of fetal size in our developing urban
      population of uncomplicated births.

PMID- 15168323
TI  - Chemokines Rantes and interleukin-8 in the perinatal period: changes in serum
      concentrations.
AB  - Chemokines, a superfamily of polypeptide mediators, are a key component of immune
      surveillance and are implicated in the initiation of the inflammatory cascade.
      This study investigated whether serum concentrations of the chemokines regulated
      upon activation, normal T-cell expressed and presumably secreted (RANTES) and
      interleukin-8 (IL-8) change in the perinatal period because of the transition
      from intra- to extrauterine life, and compared determined values in mothers (MS)
      (n = 30) with those in their fetuses (UC), neonates (day of life 1 [N1] and 4
      [N4]), and controls (CS) (n = 20). RANTES serum concentrations were higher in MS
      than in UC ( p < 0.006), N1 ( p < 0.0001), N4 ( p < 0.0001), and CS ( p <
      0.0001). IL-8 serum concentrations in MS and UC, respectively, were significantly
      lower than in N1 ( p < 0.0002 and p < 0.0007) and N4 ( p < 0.0001 and p <
      0.0001). Thus, after birth, neonatal serum concentrations of RANTES decrease,
      possibly because of elimination of the placenta (probable production site), and
      neonatal serum concentrations of IL-8 increase, possibly triggered by
      environmental antigenic stimuli to which the neonate is exposed.

PMID- 15168324
TI  - Intrauterine intussusception presenting as fetal ascites at prenatal
      ultrasonography.
AB  - Intrauterine intussusception, an uncommon cause of bowel obstruction, has rarely
      been detected by prenatal ultrasonography. We report two cases of intrauterine
      intussusception after gestation, which presented as isolated fetal ascites at 30
      weeks of gestation by ultrasonography. In case 1, on the follow-up
      ultrasonography at 32 weeks of gestation, the previously observed ascites had
      disappeared, whereas the echogenicity of the bowel was increased without any sign
      of dilation, suggesting the presence of meconium peritonitis. The fetus was
      delivered at 39 weeks. In case 2, however, the amount of fetal ascites became
      increased, and the fetus was delivered at 34 weeks of gestation. After delivery,
      both infants were surgically explored with resection of the ileum with end-to-end
      anastomosis because of intrauterine intussusception and ileal atresia. From the
      experience of these cases, we suggest that the ultrasonographic finding of
      isolated or transient fetal ascites might contribute to the early diagnosis and
      management of intrauterine intussusception.

PMID- 15168326
TI  - Dipeptidyl peptidase IV (DPPIV) activity in the tear fluid as an indicator of the
      severity of corneal injury: a histochemical and biochemical study.
AB  - Comparative histochemical and biochemical studies on the catalytically active
      protease Dipeptidyl peptidase IV (DPPIV), have been performed in the rabbit
      cornea and the tear fluid using a sensitive fluorogenic substrate, Gly-Pro-7
      amino-4-Trifluoromethyl Coumarine (AFC). In both normal and experimentally
      injured corneas, DPPIV activity was detected histochemically and in the tear
      fluid biochemically. In contrast to the normal cornea where DPPIV activity was
      absent and in the tear fluid where it was low, during continuous wearing of
      contact lenses or repeated irradiation of the cornea with UVB rays, slight DPPIV
      activity appeared first in the superficial layers of the corneal epithelium,
      while later increased activity was present in the whole epithelium. This
      paralleled elevated DPPIV activity in the tear fluid. Moreover, during continuous
      contact lens wear, the increased DPPIV activity in the tear fluid was, in many
      cases, coincidental with the presence of capillaries in the limbal part of the
      corneal stroma. After severe alkali burns when corneal ulcers appeared, collagen
      fragments were active for DPPIV, which was associated with high DPPIV activity in
      the tear fluid. In conclusion, Gly-Pro-AFC was found to be useful for comparative
      histochemical and biochemical studies on DPPIV activity in the experimentally
      injured rabbit eye. Using the method of the tear film collection by a short touch
      of substrate punches to the respective site of the cornea or conjunctiva we can
      show that in experimental injuries (wearing of contact lenses, irradiation of the
      cornea with UVB rays), the damaged corneal cells were the main source for DPPIV
      activity in the tear fluid. It is suggested that the activity of DPPIV measured
      in the tear fluid might serve as an indicator of early corneal disorders, e.g.
      corneal vascularization related to contact lens wear.

PMID- 15168327
TI  - Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a
      murine model for senile osteoporosis.
AB  - SAMP6, a substrain of senescence-accelerated mice, was developed as an animal
      model for senile osteoporosis. In the present study, we investigated the bone
      morphology, together with serum calcium and bone mineral density (BMD) in SAMP6
      and age-matched normal mice SAMR1. We did not find any significant differences
      between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions
      and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral
      calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5
      months of age. The number of osteoblasts in trabecular bones was also
      significantly reduced. Swollen mitochondria and myelin-like structures were found
      in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a
      greater proportion of resting surface and less forming surface in the femoral
      endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar
      vertebra and the distal metaphysis of the femur was reduced. The number of the
      mast cells in bone marrow of the tibia significantly increased in SAMP6 mice.
      These findings indicate that the lower bone mass in SAMP6 was due to the
      reduction in osteoblast formation and suggested that mast cells in bone marrows
      play a role in the pathogenesis of senile osteoporosis.

PMID- 15168328
TI  - Comparative analysis of cell populations involved in the proliferative and
      inflammatory processes in diffuse and localised pigmented villonodular synovitis.
AB  - The aim of the present study was a comparative quantitative evaluation of cell
      populations involved in the proliferative and inflammatory compartment in both
      localised and diffuse pigmented synovitis villonodularis (PVNS). 15 cases of each
      localised and diffuse PVNS were examined by flow cytometry, immunohistochemistry,
      double immuno-fluorescence and confocal microscopy with quantitative evaluation
      of CD3-, CD4-, CD8-, CD20-, CD57-, CD55-, CD68-, CD163- and h4Ph positive (+)
      cells. The proliferative compartment of localised and diffuse PVNS was mainly
      composed of double-positive CD68+/h4Ph+ (CD163+/CD55+) synoviocytes. The number
      of double-positive synoviocytes for macrophage and fibroblast markers was
      significantly higher in diffuse compared to localised PVNS. The accompanying
      inflammatory infiltrate showed a predominance of cytotoxic cells (CD8+, CD57+),
      whereby the number of CD3+ and CD20+ cells was significantly higher in localised
      PVNS. The number of CD57+ NK cells was significantly higher in diffuse PVNS. The
      proliferating macrophage- like synovial cells and the cytotoxic lymphocytes could
      contribute to the aggressive behaviour of localised and diffuse PVNS. Moreover,
      with regard to the quantitative differences in cell composition between diffuse
      and localised PVNS and their different clinical behaviour, further studies should
      continue to analyse localised and diffuse PVNS separately.

PMID- 15168325
TI  - Age-related maculopathy: a genomewide scan with continued evidence of
      susceptibility loci within the 1q31, 10q26, and 17q25 regions.
AB  - Age-related maculopathy (ARM), or age-related macular degeneration, is one of the
      most common causes of visual impairment in the elderly population of developed
      nations. In a combined analysis of two previous genomewide scans that included
      391 families, containing up to 452 affected sib pairs, we found linkage evidence
      in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of
      families and have performed an integrated analysis incorporating 530 families and
      up to 736 affected sib pairs. Under three diagnostic models, we have conducted
      linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an
      autosomal dominant model) and nonparametric (Sall statistic) methods. There is
      ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25
      regions. If we treat the third set of families as a replication set, then two
      regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all
      our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD
      or Sall scores > or =2.0. Within the 1q31 region, we observed an HLOD of 2.72
      (genomewide P=.061) under our least stringent diagnostic model, whereas the 17q25
      region contained a maximal HLOD of 3.53 (genomewide P=.007) under our
      intermediate diagnostic model. We have evaluated our results with respect to the
      findings from several new independent genomewide linkage studies and also have
      completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking
      history, and age at onset as stratifying covariates. The OSAs generate the
      interesting hypothesis that the effect of smoking on the risk of ARM is
      accentuated by a gene in the 10q26 region--a region implicated by four other
      studies.

PMID- 15168329
TI  - Corticosterone 21-acetate in vivo induces acute stress in chicken thymus: cell
      proliferation, apoptosis and cytokine responses.
AB  - In vivo effects of acute stress induced by corticosterone 21-acetate in male
      Gallus domesticus thymus are studied and the steroid actions are evaluated in
      terms of cell proliferation, apoptosis and cytokine response in 10- and 21-day
      old chickens. Steroid treatment induced thymocyte apoptosis and cell death
      decreased in the cortical-medullar direction and was more evident in younger
      animals. 24 h after treatment, the observed effect was reversed. The mitotic
      activity and thymic cells containing cytokine-like molecules were also affected.
      Indeed, the acute stress stimulated cytokine immunoreactivity to anti-IL-1alpha,
      IL-6 and TNF-alpha antibodies both in epithelial cells and interdigitating cells
      located in medullar and cortical-medullar regions. The increased cytokine
      expression observed after 12 h was maintained after 24 h. The comparison between
      10- and 21-day-old chickens showed a lower number of cells containing cytokine
      like molecules in younger specimens. The present findings suggest that cytokines
      activated by acute stress in vivo could contribute to restoring immunological
      homeostasis and influence thymic glucocorticoid-mediated functions.

PMID- 15168330
TI  - Aberrant expression of a fetal glycoprotein 68 in hepatocellular carcinoma: a
      comparative study on the expression of alpha-fetoprotein and carcinoembryonic
      antigen.
AB  - A rat IgG2a monoclonal antibody against a stage-specific fetal glycoprotein with
      a molecular mass of 68 kDa (FGP68) was produced and applied to paraffin sections.
      This monoclonal antibody was used to compare the expression of FGP68 with that of
      both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in 75
      hepatocellular carcinomas (HCCs). Seventy-five primary HCCs from patients aged 36
      to 77 years were examined. Formalin-fixed, paraffin-embedded tissue sections were
      used for immunohistochemical analyses. Histologically, 6 cases of HCC were
      classified as type I according to the Edmondson and Steiner criteria, 57 cases as
      type II, and 12 cases as type III. The cancer tissues showed positive reactions
      with the antibody against FGP68. Approximately one-third of the HCCs (26/75)
      contained tumor cells that expressed FGP68 -(21/57 for Edmondson and Steiner type
      II; 4/12 for type III; and 1/6 for type I) - and positive immunoreactivity was
      observed in the cytoplasm of the cancer cells. Twenty-five of the 75 HCCs had
      tumor cells that expressed AFP and there was a significant correlation between
      FGP68 expression and AFP expression. Twenty-three of the 75 HCCs had tumor cells
      that expressed CEA and there was no significant correlation between FGP68
      expression and CEA expression. No positive reactions for FGP68, AFP and CEA were
      observed in samples of non-neoplastic liver tissues. Based on the possibility
      that stage-specific FGP68 plays an important role in liver embryogenesis, FGP68
      expressing tumor cells might ontogenetically revert to more primitive cells.

PMID- 15168331
TI  - The disappearance of CD34-positive and alpha-smooth muscle actin-positive stromal
      cells associated with human intra-uterine and tubal pregnancies.
AB  - In order to elucidate the change in alpha-smooth muscle actin (ASMA)-positive and
      CD34-positive stromal cells associated with pregnancy, we examined endometrial
      and Fallopian tube tissues from 40 patients including normal endometrium (n=10),
      intra-uterine pregnancy (n=10), normal Fallopian tube (n=10), and tubal pregnancy
      (n=10), using immunohistochemistry. In normal endometrium, only a few ASMA
      positive cells were focally observed. Additionally, a wide range of CD34-positive
      stromal cell abundance was observed. In normal Fallopian tube mucosa, a small to
      moderate number of both ASMA-positive and CD34-positive stromal cells was
      observed. Neither ASMA-positive nor CD34-positive stromal cells were observed
      anywhere in the decidual stroma during both intra-uterine and tubal pregnancies.
      Likewise, a varying abundance of ASMA-positive cells but no CD34-positive stromal
      cells were observed at the fetal side during both intra-uterine and tubal
      pregnancies. In conclusion, the disappearance of CD34-positive and ASMA-positive
      stromal cells may be an indicator of decidualisation induced change in the stroma
      during both intra-uterine and tubal pregnancies. ASMA-positive stromal cells at
      the fetal side associated with pregnancy may play a role in the production of
      villous extracellular matrix or regulation of blood flow.

PMID- 15168332
TI  - Expression of prostate specific membrane antigen (PSMA) in prostatic
      adenocarcinoma and prostatic intraepithelial neoplasia.
AB  - The prostatic membrane antigen (PSMA) is a protein that is expressed in the
      prostatic epithelium. We studied the expression of PSMA in a series of 55
      patients with different stages of prostate cancer and we compared the PSMA
      staining in prostate cancer cells, in high-grade prostatic intraepithelial
      neoplasia (PIN) and in histologically benign prostatic epithelium for the same
      specimen. For this purpose archival paraffin-embedded specimens were studied by
      immunohistochemistry with a monoclonal antibody 7E11-C5.3 against PSMA using the
      streptavidin-biotin method. The mean percentage of PSMA immunoreactivity was
      56.67% in prostate cancer (CaP) cells, and 48.6% in PIN cells, which was
      significantly higher than benign-appearing prostatic epithelium (5.72%) (for each
      pair, p<0.001). PSMA expression was greater in CaP with a higher Gleason score
      (p=0.01), but no relationship was found with serum PSA value. We conclude that
      PSMA overexpression is detected in high-grade PIN and is associated with a higher
      Gleason score of prostate cancer. It is a potential marker for studying
      carcinogenesis and progression of prostate cancer.

PMID- 15168333
TI  - In situ detection of cyclic AMP-phosphodiesterase activity in the heart of Lewis
      and Sprague-Dawley rats: the effect of restraint stress or amphetamine
      application.
AB  - Cyclic AMP plays an important role in heart functions under normal as well as
      pathological conditions. Since phosphodiesterase (PDE), responsible for the
      hydrolysis of cAMP, is equally important as synthesizing adenylyl cyclase, we
      decided to determine its activity by cytochemical procedure after exposure of
      rats to restraint stress or an acute dose of amphetamine. Sprague-Dawley (S-D)
      and Lewis (LE) rats, the latter known to have a deficient hypothalamo-pituitary
      adrenal axis activity, were used in order to disclose the possible significance
      of rat strain on PDE activity. Animals were divided into 3 groups: controls, rats
      treated with an acute dose of amphetamine (8 mg/kg, i.p., for 60 min) and rats
      under restraint stress for 60 min. Control hearts of both strains revealed PDE
      activity on sarcolemma of cardiomyocytes and plasmalemma of endothelial cells of
      microvessels. In LE rats we observed an additional enzyme reaction in junctional
      sarcoplasmic reticulum. In addition, cardiomyocytes of LE rats revealed a higher
      PDE activity when compared to S-D rats. Restraint stress decreased PDE activity
      in cardiomyocytes of LE rats while amphetamine markedly inhibited enzyme activity
      in cardiomyocytes of S-D rats. Endothelial PDE was more resistant to stress. Our
      results indicate differences in PDE localization and variations in sensitivity of
      myocardial cAMP-PDE of LE and S-D rat strains to restraint stress and amphetamine
      application.

PMID- 15168334
TI  - Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously
      hypertensive mature rats.
AB  - Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were
      separated into three groups (n=5 each) during 15 weeks as follows: initial
      control group (IC); final control group (FC); and telmisartan group (T) (1.2
      mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not
      different comparing untreated and telmisartan-treated SHRs. FC rats showed a
      continuous BP increase during the study while T rats reached the 15th week with a
      significantly low BP. The LV mass index was significantly smaller in the T group
      than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei
      density per area and the cardiomyocyte mean cross-sectional area were smaller in
      the T group than in both the IC and FC groups. Intramyocardial artery densities
      (per area and per volume) were greater in the T group than in untreated SHRs, but
      myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects
      on BP and also on the hypertension target organs, heart and kidney, are
      favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular
      hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to
      the intramyocardial microcirculation.

PMID- 15168335
TI  - Immuno-histochemical expression of alpha1, alpha2 and alpha3 integrin subunits
      during angiogenesis in vitro.
AB  - Aortic explants were obtained from mouse fetuses and cultured in collagen gels.
      Immuno-fluorescence microscopy, antibodies (anti alpha1, alpha2 and alpha3
      integrin subunits) were used. Fibroblastic cells migrated from the aortic explant
      after one day of cultivation. The migrating cells located in the peripheral part
      of the aortic explant were positive for alpha1 and alpha2 integrin subunit
      antibodies. Immuno-fluorescence-positive staining for the alpha3 integrin subunit
      antibody was clearly seen in the migrating cells located near the aortic explant
      and surrounding tube-like structures. In an immuno-electron microscope study
      performed by pre-embedding immuno labeling, gold particles associated with the
      alpha3 integrin subunit were found to reside on the membranes of the cells
      surrounding the capillary-like tubes. Two synthetic peptides, GRGDSP (Gly-Arg-Gly
      Asp-Ser-Pro) and KDGEA (Lys-Asp-Gly-Glu-Ala), were added to the growth medium to
      study their effects on cell migration. KDGEA, a compound containing the
      recognition sequence for alpha2beta1 integrin, decreased cell migration, while
      GRGDSP exhibited no effect. The migration of fibroblastic cells is an important
      phenomenon for tube formation. The present study suggested that the alpha1 and
      alpha2 integrin subunits are both involved in the cell migration, and more
      specifically, that the alpha2 integrin subunit participates in cell migration
      through the KDGEA sequence. The alpha3 integrin subunit played a role in tube
      formation.

PMID- 15168336
TI  - Distribution and role of CD34-positive stromal cells and myofibroblasts in human
      normal testicular stroma.
AB  - CD34-positive stromal cells are distributed in various organs including breast,
      Fallopian tubes, thyroid gland, colon, pancreas, and uterine cervix. To elucidate
      the distribution of CD34-positive stromal cells, smooth muscle cells, and
      myofibroblasts in normal human testis, we examined 48 testes obtained by autopsy
      and operation, including five fetal, one neonatal, and 42 adult cases without
      evident testicular lesions, using a streptavidin-biotin immunoperoxidase
      technique. The expression of alpha-smooth muscle actin (ASMA), h-caldesmon, CD34,
      and CD31 were immunohistochemically examined in all cases. The tunica albuginea
      and the inner layer of seminiferous tubules in adult testis were predominantly
      composed of myofibroblasts. Smooth muscle cells were also scattered throughout
      these sites in some cases. CD34-positive stromal cells were abundant, and they
      formed a reticular network around the seminiferous tubules and Leydig cells as
      well as the outer layer of seminiferous tubules. Moreover, myofibroblasts and the
      CD34 reticular network were already present in the testicular stroma during fetal
      or neonatal development. Double immunostaining of fetal, neonatal and adult
      testes using ASMA and CD34 confirmed that myofibroblasts and CD34-positive
      stromal cells were present in the inner and outer layers of peritubular tissue,
      respectively. This distribution and cytological identification was also confirmed
      by an ultrastructural study of four cases. Finally, CD34-positive stromal cells
      and myofibroblasts are major components of human testicular stroma.

PMID- 15168337
TI  - Nuclear localization of aldolase A in pig cardiomyocytes.
AB  - The subcellular localization of the muscle aldolase (aldolase A) in
      cardiomyocytes was determined immunocytochemically by light and electron
      microscopy. The enzyme was localized in the cytoplasm and also in cardiomyocyte
      nuclei. Inside the nuclei it was preferentially localized in the heterochromatin
      region. The nuclear localization was confirmed by the measurement of aldolase
      activity in subcellular fractions of a heart muscle, and in isolated nuclei of
      cardiomyocytes. There was no detectable aldolase activity in isolated
      cardiomyocyte nuclei fractions if the fraction was not preincubated with a
      solution containing Triton X-100 and KCl. The calculated concentration of
      aldolase in the nucleus was about 0.6 micro M. This paper is the first report on
      the localization of aldolase A inside cardiomyocyte nuclei.

PMID- 15168338
TI  - Prognostic value of apoptosis in breast cancer (pT1-pT2). A TUNEL, p53, bcl-2,
      bag-1 and Bax immunohistochemical study.
AB  - Apoptosis or programmed cell death produces cells breaking into several fragments
      of nuclei, cytoplasm or both nuclei and cytoplasm, known as apoptotic bodies
      which can be visualized in haematoxylin-eosin staining. Some genes (promoters and
      suppressors) control this process and certain mutations may induce the expression
      of abnormal proteins, which can be detected by immunohistochemical staining.
      Apoptosis can be detected by the TUNEL method either identifying apoptotic bodies
      or cells at the initial stages of the fragmentation process. We have studied 186
      cases of infiltrating ductal breast carcinoma, stages pT1-pT2, and analysed the
      prognostic significance of tumour recurrence and overall survival of apoptotic
      index (AI) through univariate and multivariate analysis. We have also studied the
      immunohistochemical protein expression of apoptosis promoter and suppressors gene
      (p53, nuclear expression; bcl-2 and Bax, cytoplasm expression; BAG-1, nuclear and
      cytoplasm expression). The results indicate prognostic significance of p53 and
      bcl-2 related to patient death and bcl-2 and tumour size to tumour recurrence,
      bcl-2 acting as a protector factor (apoptotic suppressor) in both situations. On
      the other hand, we have not found useful prognostic information of AI either to
      tumour recurrence or overall survival in univariate or multivariate studies. In
      this study, Bax expression does not provide a new prognostic role in breast
      carcinoma, although it contrasts to the bcl-2 action and accelerates death.

PMID- 15168339
TI  - Pulmonary lymphoid lesions in an experimental model of collapsing glomerulopathy
      in rats.
AB  - The characterization of lung damage in an experimental model of collapsing
      glomerulopathy (CG) in rats is described. METHODS: 12 rats were divided into two
      groups and injected intravenously (iv) with 1 mg/saline in a final volume of 1
      ml/ day in the tail vein for 5 days, with fractionated serum from control and CG
      subjects. Proteinuria was quantified, and the Glomerular filtration rate was
      calculated based on creatinine clearance (CC). Rats were sacrificed by perfusion
      fixation at day 5. RESULTS: Rats injected with serum from CG patients developed
      proteinuria (p<0.001). A decrease in CC (0.68+/-0.19) in these rats was also
      observed. Glomerular tuft retraction and mesangial proliferation was observed in
      all rats receiving serum from the CG patients. Peribronchiolar infiltrate
      integrated mainly by lymphocytes, was identified in all CG rats. In some areas
      this infiltration disrupted the basement membrane and damaged the epithelium. No
      histopathological abnormalities in the kidney or lungs were found in rats
      receiving control serum. CONCLUSION: Patchy pulmonary lymphoid infiltrates were
      found in the CG model. Up to now there was no information about pulmonary
      lymphoid infiltration in CG patients. Besides fluid overload due to renal
      insufficiency or a nephrotic syndrome, other causes of pulmonary involvement in
      CG patients should be explored.

PMID- 15168340
TI  - Dietary aluminium and renal failure in the koala (Phascolarctos cinereus).
AB  - The study investigated the link between the potentially nephrotoxic levels of
      aluminium ingested in the natural diet of eucalypt leaves by koalas in the
      Adelaide Hills, South Australia, and the high incidence of renal failure in
      koalas within this habitat. Routine histology of kidney specimens revealed no
      pathologies at the light microscopic level and contrasted sharply with the
      clinical signs of renal failure. However staining with solochrome azurine and
      Perl's Prussian blue showed aluminium was present in some proximal convoluted
      tubules in all specimens. Aluminium was also found in bone samples. The presence
      of aluminium in bone and kidney tissues was confirmed using electron dispersive x
      ray analysis with transmission and scanning electron microscopy. Ultrastructural
      changes, including a decrease in lysosomal numbers, were seen in proximal
      convoluted tubules and these changes were shown to coincide with the presence of
      aluminium. No aluminium was found in koalas that died from causes other than
      renal failure. It was concluded that renal failure in the koalas of the Adelaide
      Hills is characterised by the presence of aluminium in the kidneys and bone and
      it is probably related to the high levels of aluminium in their restricted diet
      of eucalypt leaves. However, it is not known if the presence of aluminium is the
      cause or effect of the renal failure. The study is the first account where
      aluminium ingested as part of the natural diet of mammals has been shown to
      accumulate in the animal and be implicated with nephrotoxicity.

PMID- 15168341
TI  - Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA
      expression.
AB  - The aim of the study was to examine numerous features of argyrophilic proteins
      related to nucleolar organizer regions (AgNORs) in thyroid tumors, relate them to
      PCNA expression and evaluate which of these features might be useful in the
      diagnosis of thyroid lesions. Paraffin sections of 100 thyroid tumors were silver
      stained and divided into 9 groups: nodular goiter (NG), simple adenoma (SA),
      microfollicular adenoma (MFA), follicular carcinoma (FC), follicular variant of
      papillary carcinoma (PC-F), classical variant of papillary carcinoma (PC-C),
      Hurthle cell adenoma (HA), Hurthle cell carcinoma (HC), and anaplastic carcinoma
      (AC). The slides were analyzed with the computerized system for image analysis. A
      weak correlation was found between PCNA expression and AgNOR size. AC differed
      significantly from all other examined groups in many features of AgNOR dots.
      Hurthle cell neoplasms were characterized by the presence of a usually single and
      relatively large dot. With respect to diagnosing follicular lesions, we found
      that the evaluation of the total area of dots in the nucleus seemed to be the
      most useful for discrimination: the assumption of 4.9 micro m2, as a cut-off
      value, allowed a correct classification of 77% of FC cases. Computer-aided
      morphometric analysis of AgNORs may be useful in the diagnostics of thyroid
      lesions.

PMID- 15168342
TI  - Effect of octreotide on expression of calcitonin gene in cultured cells of
      medullary thyroid carcinoma.
AB  - The studies were performed on cultured TT cells, originating from medullary
      thyroid carcinoma and producing calcitonin (CT) and CT gene-related peptide
      (CGRP), synthesized on the template of the same gene. Addition of octreotide (a
      synthetic somatostatin analogue) to the cell culture augmented amounts of CGRP
      mRNA and of CGRP protein in the cells as well as increased levels of CGRP in the
      culture medium. In contrast, amounts of CT mRNA and of CT protein in the cells as
      well as levels of CT in the medium remained unchanged. The results showed that
      octreotide stimulates transcription and alternate splicing of the CT gene.

PMID- 15168343
TI  - Ultrastructural localization of integrin subunits alpha3 and alpha6 in
      capillarized sinusoids of the human cirrhotic liver.
AB  - Normal liver sinusoids are not lined by a basement membrane (BM). In contrast, in
      the course of development of liver cirrhosis, a structured BM is formed de novo
      in the space of Disse. This BM contributes to the inhibition of the metabolic
      function of the liver but the pathogenic background of the formation of this
      perisinusoidal BM is still unclear. Integrins of the beta1-class are generally
      essential for BM stability and some of them (such as alpha2beta1, alpha3beta1 and
      alpha6beta1) appear de novo in the perisinusoidal space of the cirrhotic liver.
      Their cellular distribution in capillarized sinusoids as well as the correlation
      between their cellular distribution and the formation of the microvascular BM in
      the cirrhotic liver has not been shown at the ultrastructural level. In the
      present work we aimed to clarify this issue. We focused on integrins alpha3beta1
      and alpha6beta1 and localised them ultrastructurally in human cirrhotic liver
      microvessels using postembedding immunogold which allows the ultrastructural
      localization of antigens with high resolution in the tissue. The newly formed
      basement membrane of capillarized sinusoids was visualized by means of fixation
      with addition of tannic acid, which enables the visualization of structures of
      the extracellular matrix with the highest resolution. Also, we carried out
      laminin detection using postembedding immunogold. Our results show that both
      alpha3beta1 and alpha6beta1 are expressed on the surface of both hepatocytes and
      endothelial cells, i.e. on both sides of the newly formed basement membrane. This
      latter shows zones of higher density both in close proximity to the endothelial
      and to the hepatocytic surfaces which resemble laminae densae. We propose that
      hepatocytes and endothelial cells may, therefore, by expressing such integrins,
      contribute to the formation of this pathological BM in the microvessels of the
      human cirrhotic liver. On stellate cells, which are major producers of BM
      components, both integrins alpha3beta1 and alpha6beta1 were also localized.

PMID- 15168344
TI  - Immunohistochemical expression of superoxide dismutase (MnSOD) anti-oxidant
      enzyme in invasive breast carcinoma.
AB  - The most important cellular protective mechanisms against oxidative stress are
      antioxidant enzymes. Their action is based on decomposal of reactive oxygen
      species (ROS) and their transformation to H2O2. Within the mitochondria manganese
      superoxide dismutase (MnSOD) affords the major defense against ROS. In this study
      we investigated tissue sections from 101 breast carcinomas for the
      immunohistochemical expression of MnSOD protein and these results were assessed
      in relation to various clinicopathological parameters, in order to clarify the
      prognostic value of this enzyme. The possible relationship to hormone receptor
      content, anti-apoptotic protein bcl-2, p53 and cell proliferation was also
      estimated. High expression levels were observed, as 79/101 (78,2%) cases
      expressed strong immunoreactivity. In this study MnSOD increased in a direct
      relationship with tumor grade and is therefore inversely correlated with
      differentiation (p=0.0004). Furthermore, there was a strong positive correlation
      between MnSOD expression and p53 protein immunoreactivity (p=0.0029). The
      prognostic impact of MnSOD expression in determining the risk of recurrence and
      overall survival with both univariate (long-rang test) and multivariate (Cox
      regression) methods of analysis was statistically not significant. These results
      indicate that neoplastic cells in breast carcinomas retain their capability to
      produce MnSOD and thus protected from the possible cellular damage provoked by
      reactive oxygen species. In addition, MnSOD content varies according to the
      degree of differentiation of breast carcinoma.

PMID- 15168345
TI  - Age-related changes of the ultrastructure in the cardiomyopathic hamster (UM-X7.1
      Syrian hamster) parathyroid gland.
AB  - We qualitatively and quantitatively investigated parathyroid glands of the UM
      X7.1 cardiomyopathic hamster at 1, 2, 6 and 12 months of age to compare them with
      those of the normal hamster. We found that at 1 month of age in the UM-X7.1
      hamster, the Golgi apparatus, lipid droplets and secretory granules decreased.
      There were no significant differences between the UM-X7.1 hamster and the control
      hamster at 2 months of age. At 6 months of age, the Golgi apparatus, rER and the
      secretory granules significantly increased in the UM-X7.1 hamster. At 12 months
      of age, the Golgi apparatus and lysosomes increased, while the secretory granules
      decreased. Ultrastructurally, we consider that in the UM-X7.1 hamster, the
      synthesis and release of the parathyroid at 6 months of age may be activated by
      an excessive amount of circulating catecholamine, and the functional activity of
      the parathyroid glands at 12 months of age may be depressed by the increased
      plasma calcium level. These findings suggest that the activities of the synthesis
      and release of the parathyroid hormone were the highest at 6 months of age in the
      UM-X7.1 hamster.

PMID- 15168346
TI  - Intra- and extracellular Abeta and PHF in clinically evaluated cases of
      Alzheimer's disease.
AB  - Temporal cortical sections from postmortem brains of individuals without any
      dementing condition and with different degrees of severity of Alzheimer's disease
      (AD) evaluated by the Clinical Dementia Rating scale (CDR 0-CDR 3) were analyzed
      using immunohistochemical procedures. To demonstrate the amyloid-beta-peptide
      (Abeta) deposition and the neurofibrillary pathology, two monoclonal antibodies
      were used, a human CERAD Abeta (10D5) antibody raised against the N-terminal
      region of the Abeta-peptide, and an antibody raised against paired helical
      filaments (PHF-1). The neuron cell bodies and the glial cells were also
      recognized by two polyclonal antibodies raised, respectively, against the protein
      gene peptide (PGP 9.5) and glial fibrillary acidic protein (GFAP). Directly
      related to severity of AD, progressive deposits of Abeta-peptide were found
      within cortical pyramidal-like neurons and forming senile plaques.
      Ultrastructurally, Abeta-peptide deposits were related to neuronal
      intracytoplasmic organelles, such as the ER, the mitochondria, the Nissl bodies
      and lipofuscin. We have also found that the intracellular deposition of the Abeta
      peptide is a neuropathological finding prior to the appearance of PHF
      immunoreactive structures. We suggest that the intracellular Abeta deposition in
      cortical pyramidal neurons is a first neurodegenerative event in AD development
      and that it is involved in cell dysfunction, neuronal death, and plaque
      formation.

PMID- 15168347
TI  - Transgenic mice overexpressing both amyloid beta-protein and perlecan in
      pancreatic acinar cells.
AB  - Heparan sulfate proteoglycans such as perlecan are thought to facilitate amyloid
      fibril formation. Tg3695 mice overexpress perlecan core protein in many tissues
      including the brain and pancreas. Tg13592 mice overexpress the signal plus 99
      amino acid carboxyl terminal sequences (C99) of amyloid beta-protein precursor in
      multiple tissues and develop amyloid deposits in the pancreas. To investigate a
      role of perlecan in beta-amyloidosis, we established doubly transgenic mice by
      crossing the two lines of transgenic mice. The expression levels of the two
      transgenes remained unchanged in the brain and pancreas and the doubly transgenic
      mice did not develop amyloid deposits in the brain up to 19-months of age.
      Amyloid load detected by thioflavine S in the pancreas of the doubly transgenic
      mice was not significantly different from that in the transgenic littermates
      expressing only C99. Amyloid load in the pancreas increased during aging. We
      found a positive correlation between the Abeta-immunoreactive (non-fibrillar and
      fibrillar) and thioflavine S-positive (fibrillar) Abeta deposits in the single
      (C99) but not doubly transgenic mice. Our results suggest that perlecan does not
      independently influence amyloid formation in the pancreas of the transgenic mice
      and that there may be other factors that may modulate amyloid formation together
      with perlecan.

PMID- 15168348
TI  - Lectin cytochemistry on developing rat submandibular gland primary cultures.
AB  - Lectin cytochemistry was performed in vitro on primary cultures from the rat
      submandibular gland. For this purpose, prepubertal rats (17, 27, 33 days old) of
      both sexes were used. Several types of medium supplements were tested and it was
      found that cells survived until 15 days in presence of all medium supplements and
      extracellular matrix gel. The binding patterns of all FITC/TRITC-labeled lectins,
      with and without prior sialidase digestion and deacetylation, were analyzed in a
      confocal laser scanning microscope. In particular, the occurrence of C4
      acetylated sialic acid linked to beta-galactose at day 27 and the presence of
      fucose residues at day 33 indicated that lectin probes applied to cultured cells
      give results similar to those obtained in intact tissues and can be used as
      markers of growth and differentiation.

PMID- 15168349
TI  - Immune signals in the context of secondary osteoporosis.
AB  - Bone homeostasis is maintained by a balance between bone resorption by
      osteoclasts and bone formation by osteoblasts, and alterations in bone metabolism
      can lead to diseases such as osteoporosis. Inter-cellular and intra-cellular
      signaling, originating from the immune system, the largest source of cell-derived
      regulatory signals, are involved in these processes. Immune-competent cells such
      as macrophages and lymphocytes deliver cell-cell signaling through soluble
      factors such as cytokines and through direct contact with the cells. Such
      immunological signals to the bone are transmitted primarily through osteoblasts
      or direct stimulation of osteoclasts to induce osteoclast maturation or bone
      resorption, which may in turn lead to the disequilibrium of bone metabolism.
      Inflammatory diseases such as rheumatoid arthritis are good examples of such a
      process, in which immunological signals play a central role in the pathogenesis
      of the accompanying secondary osteoporosis. We will achieve a better
      understanding of the pathogenesis of bone metabolism in osteoporosis through
      immune signaling, and thereby develop improved therapeutic strategies for these
      conditions.

PMID- 15168350
TI  - The role of apoptosis in pulmonary fibrosis.
AB  - Pulmonary fibrosis is a common response to various injuries to the lung. The
      resolution of a fibroproliferative response after lung injury is key to survival.
      Although there are various initiating factors or causes, the terminal stages are
      characterized by proliferation and progressive accumulation of connective tissue
      replacing normal functional parenchyma. Conventional therapy consisting of
      glucocorticoids or immunosuppressive drugs is usually ineffective in preventing
      progression of fibrosis. Further understanding of the molecular mechanisms of
      endothelial and epithelial cell injury, inflammatory reaction, fibroblast
      proliferation, collagen deposition and tissue remodeling, should lead to the
      development of effective treatments against pulmonary fibrosis. Evidence that
      apoptosis plays an important role in the pathophysiology of pulmonary fibrosis
      has been accumulated. We overview the role of apoptosis in each of the pathogenic
      events which have emerged from animal models and human tissue studies.

PMID- 15168351
TI  - Animal models of pheochromocytoma.
AB  - Pheochromocytomas are neuroendocrine tumors of adrenal chromaffin cells. They are
      rare in all species except rats but occur with increased frequency in several
      human familial tumor syndromes. Concurrence of pheochromocytoma with other tumors
      sometimes parallels these human syndromes in rats, bovines, horses and dogs but a
      shared genetic basis for human and spontaneously occurring animal
      pheochromocytomas has thus far not been established. Pheochromocytomas are
      inducible in rats by a variety of non-genotoxic substances that may act
      indirectly by stimulating chromaffin cell proliferation. They are not known to be
      similarly inducible in other species but arise with increased frequency in
      transgenic and knockout mice that to varying degrees recapitulate human tumor
      syndromes. Preliminary evidence suggests that homologous somatic genetic changes
      might contribute to pheochromocytoma development in humans and some mouse models.
      The nerve growth factor-responsive PC12 cell line, established from a rat
      pheochromocytoma, has for almost 30 years served as a research tool for many
      aspects of neurobiology involving normal and neoplastic conditions. Recently
      developed pheochromocytoma cell lines from neurofibromatosis knockout mice
      supplement the PC12 line and have generated additional applications. Advantages
      of the mouse lines include expression of substantial levels of the epinephrine
      synthesizing enzyme, phenylethanolamine N-methyltransferase and expression of
      high levels of the receptor tyrosine kinase, Ret, which is characteristic of
      sporadic and familial human pheochromocytomas but not of PC12 cells.
      Disadvantages include an apparently less stable phenotype. It is difficult to
      establish pheochromocytoma cell lines from any species, although the tumor cells
      persist in culture for many months. Understanding of factors that permit
      pheochromocytoma cells to proliferate might itself provide important insights for
      tumor biology.

PMID- 15168353
TI  - Role of intestinal bacterial flora in oral tolerance induction.
AB  - In healthy individuals, the immune responses against foods cannot be induced.
      This phenomenon is known as oral tolerance. We observed that the oral tolerance
      was impaired in germfree mice, and that Th2-dependent antibodies such as IgE
      could be thus induced by an orally given antigen. As a result, the germfree mouse
      was considered to be a good animal model for allergic disorder. When germfree
      mice were mono-associated with such bacteria as E.coli and B. infantis, then oral
      tolerance was restored in these gnotobiotes to a level similar to that observed
      in SPF mice. Thus, these bacterias seemed to be important in oral tolerance
      induction. In addition, the probiotics using these bacteria may be a useful
      material for the treatment of allergic disorders.

PMID- 15168352
TI  - Natural IgM antibodies, the ignored weapons in tumour immunity.
AB  - During its lifetime each multi-cellular organism is permanently exposed to
      infectious agents and transformed cells. Without an early recognition and a rapid
      elimination system, there would be no development and no life. The innate or
      natural immunity, seems to be more important for the detection of "foreign" cells
      and particles than has been thought. Even if not every transformed cell has the
      ability and potency for malignant behaviour, the important question is not, why
      malignant cells arise, but instead, why malignancy occurs so infrequently. We
      have shown in a recent paper, by using the human hybridoma technology, that
      tumour immunity is not induced by malignant cells, but instead the result of
      innate immunity and that natural IgM antibodies play an important role in
      immunosurveillance mechanisms against transformed cells in humans (Brandlein et
      al., 2003b). In this review typical features of natural IgM antibodies are
      discussed and tumour-specific reactivities and different apoptotic functions on
      epithelial cancer cells are illustrated.

PMID- 15168354
TI  - Phosphatidylinositide 3-kinase/AKT in radiation responses.
AB  - Ionizing or ultraviolet radiation-induced cellular survival signaling pathways
      induce development of cancer and insensitivity of tumor cells to radiation
      therapy. Accumulating evidence suggests that the phosphatidylinositide 3-kinase
      (PI3K)/AKT signal pathway is a major contributor to radioresistance. In many cell
      types PI3K/AKT signaling is a key cytoprotective response downstream of the EGFR
      family receptors and mediated carcinogenesis. Cytokines, such as HGF, IGF-I, and
      IL-6 also protects cells against apoptosis induced by radiation through PI3K/AKT
      pathway. The mechanics by which PI3K/AKT signaling functions in radiation
      responses may include its regulation of mitochondrial proteins, transcription
      factors, translation machinery, and cell-cycle progression. In addition, cross
      talk between the PI3K/AKT pathway and mitogen-activated protein kinases, protein
      kinase A, and protein kinase C signal pathway may also play an important role.

PMID- 15168355
TI  - Expression of MAL and MAL2, two elements of the protein machinery for raft
      mediated transport, in normal and neoplastic human tissue.
AB  - Polarized transport of lipids and proteins to the apical and basolateral membrane
      subdomains is essential for the functioning of epithelial cells. Apical transport
      is mediated by a direct route from the Golgi and an indirect route, referred to
      as transcytosis, involving the transport of the protein to the basolateral
      membrane followed by its internalization and subsequent transcellular transport
      to the apical subdomain. MAL and MAL2 have been demonstrated to be essential
      components of the machinery for the direct and indirect routes, respectively.
      Herein, we review the range of expression of MAL and MAL2 in normal human tissue
      and compare it with that of neoplastic tissue. Our analysis provides insight into
      the potential use of MAL- and MAL2-mediated pathways in many types of epithelial
      cells as well as in nonepithelial cells. In addition, the specific alterations in
      MAL and/or MAL2 expression observed in specific types of carcinoma provides a
      basis to understand the loss of the polarized phenotype that frequently
      accompanies the neoplastic transformation process. This points out potential
      applications of MAL and MAL2 as markers for tumor characterization.

PMID- 15168357
TI  - Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and
      recent developments.
AB  - It has been suggested that neuroendocrine (NE) cells provide paracrine stimuli
      for the propagation of local carcinoma cells and that NE differentiation is
      associated with the progression of prostate cancer toward an androgen-independent
      state. Apoptosis comprises a critical intracellular defense mechanism against
      tumorigenic growth and is associated with a number of changes in the elemental
      content of the cell. The neuropeptides bombesin and calcitonin, which inhibit
      etoposide-induced apoptosis, also inhibit the etoposide-induced elemental changes
      in prostate carcinoma cells. This important fact strengthens the link between
      apoptosis and changes in the intracellular elemental content. This protective
      effect on etoposide-induced apoptosis appears to be quite similar in androgen
      dependent and androgen-independent cell lines. This confirms that neuropeptides
      confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity
      to neuroendocrine cells. It can therefore be speculated that certain
      neuroendocrine peptides can increase the survival and further growth of
      neighboring cells and may thereby contribute to the aggressive clinical course of
      prostate tumors containing neuroendocrine elements. In addition, this correlation
      provides an objective basis for the study of neuropeptide target points and may
      be helpful for alternative therapeutic protocols using neuropeptide inhibitors in
      the treatment of patients with advanced prostatic carcinoma. The culture
      techniques described were, thus, designed in order to achieve two important
      goals. First, the development of an in vitro model that allows an approach to
      neuroendocrine differentiation in prostate cancer and its role in apoptosis
      blockage. Second, the method has been designed in order to permit rapid
      cryofixation of intact cell monolayers for subsequent x-ray microanalysis.

PMID- 15168356
TI  - Angiogenesis and the role of bone marrow endothelial cells in haematological
      malignancies.
AB  - Increased microvessel density (MVD) has been observed in the bone marrow (BM) of
      patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid
      leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the
      net result of cumulative phases of angiogenesis and angio-regression and is as
      such not an indicator of the ongoing angiogenesis at the time of biopsy. There
      is, therefore, a need for additional methods that allow the estimation of ongoing
      angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin
      embedded tissue to determine the endothelial proliferation fraction. The BM
      endothelial cells, as a component of the BM stroma, have a close interaction with
      the malignant cells. In MM, for example, they are involved in the specific homing
      and are a source of paracrine growth factors. Targeting the BM microvessels will
      not only influence the nutrient and oxygen supply, but will in addition reduce
      the growth stimuli provided by the EC.

PMID- 15168359
TI  - Signalling mechanisms of anoikis.
AB  - Apoptosis following loss of cell anchorage ('anoikis') is of relevance for
      development, tissue homeostasis and disease. Integrins regulate cell viability
      through their interaction with the extracellular matrix and they can sense
      mechanical forces arising from the matrix and convert these stimuli to chemical
      signals capable of modulating intracellular signal transduction. Recently it has
      been shown that protein kinase signalling pathways and apoptosis-related
      molecular control anoikis both positively and negatively. Focal adhesion kinase,
      when activated by integrins, can suppress anoikis. Phosphatidylinositol 3
      kinase/Akt and mitogen-activated protein kinase may mediate the anoikis
      suppressing effects of cells. Conversely, the stress-activated protein kinase/Jun
      amino-terminal kinase pathway promotes anoikis. In addition, certain bcl-2 and
      bcl-2-related proteins may also participate in the regulating of anoikis. In this
      review, molecular mechanisms of signal pathway inducing and perpetuating
      detachment-induced apoptosis will be discussed with special emphasis on the role
      of integrins, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, mitogen
      activated protein kinase and bcl-2 family members.

PMID- 15168358
TI  - Primary central nervous system lymphomas in immunocompetent patients.
AB  - Primary Central nervous system lymphoma is a rare non-Hodgkin's tumor of the
      brain that has been traditionally found in patients with immunodeficiency
      syndromes. However, there are several immunocompetent patients that have also
      been reported with this neoplasm. In this group of patients, the mean age of
      diagnosis is around 60-year old, with a very slight predominance in women.
      Macroscopically, most of the tumors are unique and mainly located in the
      supratentorial region in the proximity of the cerebrospinal fluid circulation.
      The typical histological pattern is a perivascular distribution of tumor cells,
      within a network of reticulin fibers. Even though they are usually well defined
      masses, it is not rare to find tumor invasion beyond the macroscopic margin.
      Coagulative necrosis is not as common as in immunodeficiency-related cases.
      Immunohistochemistry has demonstrated that most of the tumor cells are B
      lymphocytes and the electron microscopic findings do not differ from those
      reported in systemic non-Hodgkin's lymphomas. There are several histological
      classifications of these tumors, some of them with recent modifications to
      facilitate the analysis, but unfortunately, up now with a little or no clinical
      significance. The diagnosis is based on the histological study of the specimen
      obtained mainly through a Stereotactic biopsy. The treatment is based on a
      combination of chemotherapy followed by radiotherapy, but the mortality rate is
      still high.

PMID- 15168360
TI  - Effects of thyroid hormones on Leydig cells in the postnatal testis.
AB  - Thyroid hormones (TH) stimulate oxidative metabolism in many tissues in the body,
      but testis is not one of them. Therefore, in this sense, testis is not considered
      as a target organ for TH. However, recent findings clearly show that TH have
      significant functions on the testis in general, and Leydig cells in particular;
      this begins from the onset of their differentiation through aging. Some of these
      functions include triggering the Leydig stem cells to differentiate, producing
      increased numbers of Leydig cells during differentiation by causing proliferation
      of Leydig stem cells and progenitors, stimulation of the Leydig cell
      steroidogenic function and cellular maintenance. The mechanism of action of TH on
      Leydig cell differentiation is still not clear and needs to be determined in
      future studies. However, some information on the mechanisms of TH action on
      Leydig cell steroidogenesis is available. TH acutely stimulate testosterone
      production by the Leydig cells in vitro via stimulating the production of
      steroidogenic acute regulatory protein (StAR) and StAR mRNA in Leydig cells; StAR
      is associated with intracellular trafficking of cholesterol into the mitochondria
      during steroid hormone synthesis. However, the presence and/or the types of TH
      receptors in Leydig cells and other cell types of the Leydig cell lineage is
      still to be resolved. Additionally, it has been shown that thyrotropin-releasing
      hormone (TRH), TRH receptor and TRH mRNA in the testis in many mammalian species
      are seen exclusively in Leydig cells. Although the significance of the latter
      observations are yet to be determined, these findings prompt whether hypothalamo
      pituitary-thyroid axis and hypothalamo-pituitary-testis axis are short-looped
      through Leydig cells.

PMID- 15168361
TI  - On the role of the islets of Langerhans in pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease characterized by a dismal prognosis
      with most patients dying within six months after diagnosis. Surgery is an option
      in less than one in five of these patients, and even with tumor resection the
      majority of patients succumb to the disease. Other effective treatment options
      are not available. Common features of pancreatic cancer are severe cachexia,
      marked insulin resistance and diabetes mellitus. Several studies have
      demonstrated connections between pancreatic cancers and the endocrine pancreas
      and this has raised questions regarding the role of the islets of Langerhans in
      pancreatic adenocarcinoma. This manuscript reviews the recent literature in this
      field and addresses several questions regarding the interaction between the
      islets of Langerhans and pancreatic cancer. This review considers the
      histological findings in pancreatic cancer, cell culture and animal experiments,
      the four islet cell types and the hormones they secrete, as well as the influence
      of the arachidonic acid pathways on islet cell function and pancreatic cancer.
      While pancreatic adenocarcinomas are ductal in nature, the cell of origin has not
      been identified and there is even some evidence that the islets may harbor the
      precursor cell. Considerable evidence suggests that the diabetes is caused by the
      tumor, while other studies have identified diabetes as a risk factor. Clearly,
      the islets are important in many aspects of this disease. However, even though
      progress has been made, some questions regarding the interaction of pancreatic
      cancer and the endocrine pancreas remain unanswered.

PMID- 15168363
TI  - Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and
      environmental influences.
AB  - Although the incidence and prevalence of ulcerative colitis and Crohn's disease
      are beginning to stabilize in high-incidence areas such as northern Europe and
      North America, they continue to rise in low-incidence areas such as southern
      Europe, Asia, and much of the developing world. As many as 1.4 million persons in
      the United States and 2.2 million persons in Europe suffer from these diseases.
      Previously noted racial and ethnic differences seem to be narrowing. Differences
      in incidence across age, time, and geographic region suggest that environmental
      factors significantly modify the expression of Crohn's disease and ulcerative
      colitis. The strongest environmental factors identified are cigarette smoking and
      appendectomy. Whether other factors such as diet, oral contraceptives,
      perinatal/childhood infections, or atypical mycobacterial infections play a role
      in expression of inflammatory bowel disease remains unclear. Additional
      epidemiologic studies to define better the burden of illness, explore the
      mechanism of association with environmental factors, and identify new risk
      factors are needed.

PMID- 15168364
TI  - From symptom to diagnosis: clinical distinctions among various forms of
      intestinal inflammation.

PMID- 15168365
TI  - Clinical relevance of advances in genetics and pharmacogenetics of IBD.
AB  - Crohn's disease and ulcerative colitis result from an inappropriate response of
      the mucosal immune system to the normal enteric flora in a genetically
      susceptible individual. During the past decade, exciting progress has been made
      in our understanding of the contribution of genetics to inflammatory bowel
      disease susceptibility and phenotype. This article reviews recent advances in the
      genetics of inflammatory bowel disease and explores how they might impact on
      clinical practice. Current knowledge of the genetic basis for disease
      susceptibility, phenotype, and response to therapy is explored and the factors
      currently limiting the translation of this knowledge to clinical practice is
      discussed.

PMID- 15168366
TI  - Inflammatory bowel diseases in pediatric and adolescent patients: clinical,
      therapeutic, and psychosocial considerations.
AB  - Inflammatory bowel diseases (Crohn's disease and ulcerative colitis) primarily
      affect young adults, but in 15%-25% of cases, the initial disease starts in
      childhood. Many aspects of inflammatory bowel disease, including initial
      evaluation, nutritional support, medical and surgical intervention, and the
      direction of future research, are encountered in both adult and pediatric
      patients. However, it is important to delineate issues specific to pediatric
      patients, especially growth velocity impairment, derangements in and treatment of
      abnormal bone mineralization, and transitional care issues; the lack of extensive
      randomized, controlled pediatric therapeutic trials is also a concern. This
      article reviews the epidemiology of pediatric inflammatory bowel disease
      incidence and prevalence worldwide, clinical issues (including impairments of
      growth velocity and bone density), diagnostic and therapeutic interventions, and
      psychosocial issues unique to pediatric patients. Future research directions
      defined by the North American Society for Pediatric Gastroenterology, Hepatology,
      and Nutrition and opportunities provided by existing pediatric research databases
      are highlighted.

PMID- 15168367
TI  - Endoscopy in inflammatory bowel diseases.
AB  - A correct diagnosis, adequate assessment of disease activity, avoidance of
      surgery by endoscopic interventions, and effective cancer surveillance make
      endoscopy crucial in the management of inflammatory bowel diseases (IBDs).
      Impressive technical developments of several endoscopic techniques over the past
      few decades have allowed a detailed visual impression of the affected gut and
      enable tissue sampling and various therapeutic interventions. Here we propose
      guidelines for endoscopy in inflammatory bowel disease, and review all currently
      available endoscopic techniques relevant to the proper treatment of IBD patients.

PMID- 15168368
TI  - Advances in the treatment of Crohn's disease.
AB  - The medical therapy of Crohn's disease has improved considerably in recent years.
      In large part, this is due to the introduction of new efficacious agents, both
      "biologics" and traditional small molecules. Further study of older drugs has
      also advanced our ability to devise the optimum approach to individual Crohn's
      disease patients by better clarifying the benefits, adverse effects, and means to
      optimize doses of established medications. In this review, we present an evidence
      based approach to the medical management of active Crohn's disease, Crohn's
      disease in remission, and perianal Crohn's disease that emphasizes recent
      advances that have come from the results of randomized controlled clinical
      trials.

PMID- 15168369
TI  - Medical therapy for ulcerative colitis 2004.
AB  - There continue to be evolutionary changes in the management of ulcerative colitis
      despite the fact that, aside from a variety of aminosalicylate formulations, no
      new therapies have been approved over the past few decades. Nevertheless, debates
      continue regarding the optimization of treatment with aminosalicylates and the
      short- and long-term benefits of immunomodulation in ulcerative colitis. This
      article focuses on the most recent clinical studies pertaining to the management
      of ulcerative colitis and explores both the advances and controversies pertaining
      to aminosalicylate therapy, corticosteroids, cyclosporine, and the purine
      antimetabolites. Novel therapeutic approaches--including preliminary experience
      with biological therapies directed at tumor necrosis factor and other cytokines,
      adhesion molecules, growth factors, and probiotics--will be reviewed. Recent data
      regarding potential chemoprevention in long-standing ulcerative colitis and
      management of postoperative complications and pouchitis will also be discussed.

PMID- 15168370
TI  - Optimizing anti-TNF treatment in inflammatory bowel disease.
AB  - Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor
      necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is
      indicated in refractory luminal and fistulizing Crohn's disease. In patients with
      luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in
      fistulizing disease, an i.v. loading therapy of 5 mg/kg at weeks 0, 2, and 6 is
      advocated. Because the majority of patients will relapse if not re-treated, a
      long-term strategy is necessary. The optimal long-term approach is systematic re
      treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is
      possible but is less efficacious and frequently is associated with problems
      resulting from the formation of antibodies to infliximab (ATI). If treatment is
      episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6
      mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that
      systematic maintenance with 8 weekly doses of infliximab decreases the rate of
      complications, hospitalizations, and surgeries. These effects probably are
      achieved thanks to thorough healing of the bowel. Infliximab also is indicated in
      treating corticosteroid-dependent Crohn's disease and extraintestinal
      manifestations of Crohn's disease. There are no data yet that support its use as
      first-line therapy. The data in ulcerative colitis (UC) are conflicting and we
      should await the results of 2 large controlled trials (ACT1 and ACT2) to position
      infliximab in the treatment of UC. Other anti-TNF strategies have been less
      effective than infliximab in the treatment of IBD until now. The results with
      thalidomide are promising but much more research into small molecules inhibiting
      TNF and other proinflammatory cytokines is necessary. Safety problems with
      antibody treatment mainly concern immunogenicity leading to infusion reactions,
      loss of response, and serum sickness-like delayed infusion reactions. The rate of
      opportunistic infections is increased mainly in patients treated concomitantly
      with immunosuppression. Other adverse events associated with anti-TNF strategies
      are demyelinating disease and worsening of congestive heart failure. Malignancy
      rates in patients treated with anti-TNF strategies do not seem to be increased.

PMID- 15168371
TI  - Current concepts and controversies in surgery for IBD.
AB  - Surgery improves the quality of life in patients with Crohn's disease (CD) and
      cures patients with chronic ulcerative colitis (CUC). There are several surgical
      controversies primarily involving techniques and long-term outcomes. Some debates
      are long standing; whether to perform a double-stapled ileal pouch-anal
      anastomosis (IPAA) or a mucosectomy and hand-sewn anastomosis, and whether to
      divert or not to divert in patients with CUC undergoing an IPAA. Other issues are
      more recent, such as the effects of age, pregnancy, pouch salvage, and
      laparoscopic IPAA. In patients with Crohn's disease the anastomosis technique,
      the management of perianal disease, and the role of laparoscopic surgery are
      topics of debate. This review shows the current concepts and controversies in the
      surgical management of patients with CUC or CD.

PMID- 15168372
TI  - Therapeutic manipulation of the enteric microflora in inflammatory bowel
      diseases: antibiotics, probiotics, and prebiotics.
AB  - Crohn's disease, ulcerative colitis, and pouchitis are caused by overly
      aggressive immune responses to a subset of commensal (nonpathogenic) enteric
      bacteria in genetically predisposed individuals. Clinical and experimental
      studies suggest that the relative balance of aggressive and protective bacterial
      species is altered in these disorders. Antibiotics can selectively decrease
      tissue invasion and eliminate aggressive bacterial species or globally decrease
      luminal and mucosal bacterial concentrations, depending on their spectrum of
      activity. Alternatively, administration of beneficial bacterial species
      (probiotics), poorly absorbed dietary oligosaccharides (prebiotics), or combined
      probiotics and prebiotics (synbiotics) can restore a predominance of beneficial
      Lactobacillus and Bifidobacterium species. Current clinical trials do not fulfill
      evidence-based criteria for using these agents in inflammatory bowel diseases
      (IBD), but multiple nonrigorous studies and widespread clinical experience
      suggest that metronidazole and/or ciprofloxacin can treat Crohn's colitis and
      ileocolitis (but not isolated ileal disease), perianal fistulae and pouchitis,
      whereas selected probiotic preparations prevent relapse of quiescent ulcerative
      colitis and relapsing pouchitis. These physiologic approaches offer considerable
      promise for treating IBD, but must be supported by rigorous controlled
      therapeutic trials that consider clinical disease before their widespread
      clinical acceptance. These agents likely will become an integral component of
      treating IBD in combination with traditional anti-inflammatory and
      immunosuppressive agents.

PMID- 15168373
TI  - Diagnosis and management of dysplasia in patients with inflammatory bowel
      diseases.
AB  - Patients with ulcerative colitis and Crohn's colitis face an increased lifetime
      risk of developing colorectal cancer. Factors associated with increased risk
      include long duration of colitis, extensive colonic involvement, primary
      sclerosing cholangitis, a family history of colorectal cancer, and, according to
      some studies, early disease onset and more severely active inflammation. Although
      prophylactic proctocolectomy can essentially eliminate the risk of cancer, most
      patients and their physicians opt instead for a lifelong program of surveillance.
      This entails regular medical follow-up, management with antiinflammatory and
      putative chemopreventive agents, and periodic colonoscopic examinations combined
      with extensive biopsy sampling throughout the colon. The main objective of
      regular colonoscopy is to detect neoplasia at a surgically curative and
      preferably preinvasive stage, i.e., dysplasia. An initial screening colonoscopy
      should be performed 7-8 years from disease onset or immediately in patients with
      primary sclerosing cholangitis. Surveillance should then continue annually or
      biennially so long as no dysplasia is found or suspected. Biopsy specimens are
      graded pathologically as negative, indefinite for dysplasia, low-grade dysplasia,
      high-grade dysplasia, or invasive cancer. The diagnosis and grading of dysplasia
      can be very challenging and should be confirmed by an expert pathologist whenever
      intervention or a change in management is contemplated. If 1 or more biopsy
      specimens are indefinite for dysplasia, colonoscopy intervals should be reduced.
      A patient with low- or high-grade dysplasia found in a discrete adenoma-like
      polyp, but nowhere else, can be safely managed with polypectomy and accelerated
      surveillance. However, dysplasia of any grade found in an endoscopically
      nonresectable polyp and high-grade dysplasia found in flat mucosa are both strong
      indications for proctocolectomy. Evidence further suggests that the same may be
      true even of low-grade dysplasia in flat mucosa. Chromoendoscopy holds promise
      for facilitating the endoscopic detection of neoplasia. The clinical application
      of newer molecular methods to detect neoplasia, particularly gene microarrays and
      stool DNA testing, also deserve further study.

PMID- 15168374
TI  - Obesity and kidney transplantation.
AB  - There is a worldwide epidemic of obesity, and an increasing number of patients
      who are obese are presenting for solid-organ transplantation. Obesity increases
      the risk for delayed graft function and local wound complications after
      technically successful kidney transplantation. Obese patients are more likely to
      have comorbid factors leading to premature death with a functioning kidney
      transplant. We suggest the use of World Health Organization criteria when
      reporting the impact of obesity on recipients of solid-organ transplants.
      Prospective multicenter studies are indicated to evaluate long-term outcomes in
      obese patients who successfully receive a kidney transplant. Rigorous efforts
      should be made to optimize weight before and after solid-organ transplantation by
      a judicious combination of diet, exercise, minimization of steroid therapy,
      surgery, and psychological therapies.

PMID- 15168375
TI  - New-onset diabetes mellitus in transplant patients: pathogenesis, complications,
      and management.
AB  - New-onset diabetes mellitus after transplantation is characterized by decreased
      insulin secretion and increased insulin resistance secondary to the effects of
      immunosuppression. Although impaired beta cell function appears to be the primary
      mechanism of calcineurin inhibitor-induced new-onset diabetes, impaired
      peripheral glucose utilization also appears to contribute to insulin resistance
      and abnormal glucose metabolism. Because transplant recipients who develop new
      onset diabetes mellitus after transplantation are at increased risk for
      infections, cardiovascular disease, and poor patient and graft survival, all
      patients should undergo careful assessment of risk for diabetes prior to
      transplantation and regular screening for the development of hyperglycemia
      thereafter. For patients in high-risk groups, including certain ethnic
      backgrounds, older adults, and the very young, and patients with hepatitis C,
      consideration should be given to initiating immunosuppressive therapy with agents
      that are less diabetogenic. Recent guidelines include more stringent criteria for
      diagnosis and stress the importance of strict glycemic control. Diet, exercise,
      and weight management are core components of treatment with addition of oral
      hypoglycemic agents and/or insulin as needed to achieve control. Concomitant
      measures include aggressive control of lipids and blood pressure to reduce the
      risk of cardiovascular disease. New-onset diabetes after transplantation is a
      serious issue affecting patient and graft outcomes and warrants the attention of
      all health care professionals involved in assessing and managing the transplant
      recipient.

PMID- 15168376
TI  - Advanced glycation end products in kidney transplant patients: a putative role in
      the development of chronic renal transplant dysfunction.
AB  - Chronic renal transplant dysfunction is one of the leading causes of graft
      failure in kidney transplantation. A complex interplay of both alloantigen
      related and alloantigen-unrelated risk factors is believed to underlie its
      development. We propose that advanced glycation end products (AGEs) are involved
      in the development of chronic renal transplant dysfunction. AGE formation is
      associated with different alloantigen-unrelated risk factors for chronic renal
      transplant dysfunction, such as recipient age, diabetes, proteinuria,
      hypertension, and hyperlipidemia. In vitro studies have shown that AGEs induce
      the expression of various mediators associated with chronic renal transplant
      dysfunction. Furthermore, AGE-induced renal damage has been found in multiple
      experimental studies. This renal damage shows similarity to the damage found in
      chronic renal transplant dysfunction. Together, several lines of evidence support
      a role of AGEs in the development of chronic renal transplant dysfunction and
      suggest that preventive therapy with AGE inhibitors may be helpful in preserving
      renal function in transplant recipients.

PMID- 15168377
TI  - Non-enteropathic hemolytic uremic syndrome: causes and short-term course.
AB  - BACKGROUND: Nondiarrheal or Streptococcus pneumoniae-related hemolytic uremic
      syndrome (HUS) represents a heterogeneous group of disorders. This study was
      performed to: (1) describe the current incidence, causes, demographic features,
      hospital courses, and short-term outcomes of non-enteropathic HUS; (2) compare
      findings in patients with non-enteropathic HUS with those obtained from a
      contemporaneous cohort of children with enteropathic or diarrhea-associated HUS
      (D+ HUS) diagnosed and treated at the same clinical sites; and (3) identify
      clinical or laboratory features that differentiate these 2 groups and predict
      disease severity and the short-term outcome in patients with non-enteropathic
      HUS. METHODS: Data were collected from patients screened between 1997 and 2001
      for enrollment in a multicenter trial of SYNSORB Pk (SYNSORB Biotech Inc,
      Calgary, Alberta, Canada) in D+ HUS, but who were ineligible because of lack of a
      diarrhea prodrome. The following features were recorded: age; sex; ethnicity;
      prodromal symptoms; cause; nadir values for hemoglobin, hematocrit, and platelet
      count; use of dialysis; and length of hospitalization. RESULTS: Twenty-seven of
      247 children with HUS had non-enteropathic HUS (11%). Twenty-four patients (15
      boys, 9 girls), whose medical records were complete and available for review,
      comprise the study cohort. Mean age at onset was 4.2 +/- 0.9 (SE) years.
      Infection caused by S pneumoniae was diagnosed in 9 patients (38%). Dialysis was
      performed in 17 patients (71%) for 40 +/- 27 days. Median length of
      hospitalization was 22 days (range, 2 to 71 days). Children with S pneumoniae
      related HUS had a longer hospital stay than those with other causes of non
      enteropathic HUS, but all patients with S pneumoniae-related HUS recovered kidney
      function. Dialysis therapy was required more often (17 of 24 versus 59 of 145
      children; P = 0.025) and hospital stays were longer (median, 22 versus 9 days; P
      = 0.002) in children with non-enteropathic HUS compared with patients with D+ HUS
      who were enrolled in the SYNSORB Pk clinical trial. CONCLUSION: (1) The incidence
      of non-enteropathic HUS is approximately one tenth that of D+ HUS; (2) patients
      with non-enteropathic HUS require dialysis therapy more often and are
      hospitalized more than twice as long during the acute episode compared with those
      with D+ HUS; (3) infection caused by S pneumoniae accounts for nearly 40% of
      cases of non-enteropathic HUS; and (4) although S pneumoniae-related HUS is
      associated with a less favorable short-term course than other types of non
      enteropathic HUS or D+ HUS, the long-term prognosis for recovery of renal
      function appears to be good in these patients.

PMID- 15168378
TI  - The in situ expression of interleukin-8 in the normal human kidney and in
      different morphological forms of glomerulonephritis.
AB  - BACKGROUND: Interleukin-8 (IL-8) is considered a deleterious chemokine involved
      in renal injury in glomerulonephritis (GN). IL-8 may be released as a 77-amino
      acid (AA) peptide or 72-AA protein. METHODS: We evaluated gene and protein
      expression of IL-8 in 53 renal biopsy specimens from patients with GN and 9
      control kidneys. Nonradioactive in situ hybridization and reverse-transcriptase
      polymerase chain reaction (RT-PCR) were applied to detect IL-8 messenger RNA
      (mRNA). In immunohistochemistry, a double-staining technique with the use of
      antibodies against the 77-AA and 72-AA forms of IL-8, as well as glomerular cell
      antigens, was used. RESULTS: By in situ hybridization, IL-8 mRNA was detected in
      normal glomerular, tubular, and some interstitial cells. The RT-PCR study showed
      that IL-8 mRNA expression in control kidneys significantly exceeds that in
      specimens with GN (0.89 +/- 0.82 versus 0.21 +/- 0.20; P < 0.003). In control
      kidneys, major sources of 77-AA IL-8 were podocytes and endothelial cells of
      interstitial vessels, whereas tubular epithelial cells expressed minute amounts
      of 72-AA IL-8. In GN specimens, podocyte expression of 72-AA IL-8 varied notably,
      with the greatest level found in minimal change disease and the lowest level
      found in acute endocapillary GN. Conversely, increased glomerular expression of
      the 72-AA form of IL-8 was a general feature of GN, with its level significantly
      exceeding that of the 77-AA form in acute endocapillary GN (P < 0.01).
      CONCLUSION: Our results suggest that intrinsic glomerular cell production of IL
      8, in particular the 77-AA form, may be relevant for preservation of the
      glomerular architecture.

PMID- 15168379
TI  - Predialysis nephrologic care and a functioning arteriovenous fistula at entry are
      associated with better survival in incident hemodialysis patients: an
      observational cohort study.
AB  - BACKGROUND: Late nephrologist referral may adversely affect outcome in patients
      initiating maintenance hemodialysis therapy, mostly with temporary catheters that
      may further increase morbidity and mortality. Our aim was to evaluate the
      influence of 2 variables on mortality: presentation mode (planned versus
      unplanned) and type of access (arteriovenous fistula [AVF] versus temporary
      catheter) at entry. METHODS: This was a 3-center, 5-year, prospective,
      observational, cohort study of 538 incident patients. Measurements included
      presentation mode, type of access, renal function and biochemical test results at
      entry, and stratification of risk groups. Main outcome measures were mortality
      and hospitalization. RESULTS: Of 281 planned patients (52%), 73% initiated
      therapy with an AVF. Of 257 unplanned patients (48%), 70% initiated therapy with
      a catheter (P < 0.001). Multivariate Cox analysis showed that unplanned
      presentation (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.23 to
      2.44) and initiation of therapy with catheter (HR, 1.75; 95% CI, 1.25 to 2.46)
      were independently associated with greater mortality and similar HRs after
      adjusting for confounders. At 12 months, the number of deaths was 3 times higher
      in both the unplanned versus planned groups and catheter versus AVF groups. The
      joint effect of unplanned dialysis initiation and catheter use had an additive
      impact on mortality (HR, 2.89; 95% CI, 1.97 to 4.22). Greater hematocrit (HR,
      1.04; 95% CI, 1.01 to 1.09) and albumin level (HR, 1.79; 95% CI, 1.37 to 2.33)
      showed an independent association with survival, underscoring the benefits of
      predialysis care. Using Poisson regression, all-cause hospitalization (incidence
      rate ratio, 1.56; 95% CI, 1.36 to 1.79; P < 0.001) and infection-related
      (incidence rate ratio, 2.62; 95% CI, 1.91 to 3.59; P < 0.001) and vascular access
      related (incidence rate ratio, 1.49; 95% CI, 1.15 to 1.94; P < 0.003) admissions
      were higher in unplanned patients initiating therapy with a catheter than in
      planned patients initiating therapy with an AVF, after adjusting for confounders.
      CONCLUSION: Unplanned dialysis initiation and temporary catheter were
      independently associated with greater mortality rates in incident patients. The
      combined influence of both variables was associated with greater morbidity and
      mortality than either variable alone.

PMID- 15168380
TI  - Associations with predialysis vascular access management.
AB  - BACKGROUND: The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines
      encourage increasing the proportion of arteriovenous fistulae among incident
      hemodialysis patients. Achieving optimal outcomes requires predialysis out
      patient follow-up by a nephrologist, predialysis placement of a vascular access,
      and adequate maturation of the vascular access. METHODS: We assessed the effect
      of clinical factors on predialysis vascular access management in all incident
      hemodialysis patients at a single institution during a 2-year period. RESULTS: Of
      157 patients initiating dialysis therapy from January 1, 2001, to December 31,
      2002, a total of 73.2% had predialysis follow-up by a nephrologist, 46.5% had
      predialysis vascular access surgery, and 35.0% initiated their first dialysis
      session with a permanent access. Among patients using a permanent access on their
      first dialysis session, 67.3% used a fistula. Patients with diabetes were more
      likely than those without diabetes to have predialysis nephrology follow-up
      (81.5% versus 61.5%; P = 0.005), undergo predialysis vascular access surgery
      (56.5% versus 32.3%; P = 0.003), and initiate their first dialysis session with a
      fistula or graft (43.5% versus 23.1%; P = 0.008). Duration of predialysis
      nephrology follow-up was similar between patients with and without diabetes
      (median, 412 versus 300 days; P = 0.27). Patient age, sex, and race were not
      predictive of predialysis access management. CONCLUSION: Despite attempts to
      follow the K/DOQI guidelines, 65% of incident hemodialysis patients initiated
      their first dialysis treatment with a catheter. Patients with diabetes were
      significantly more likely to have predialysis follow-up by a nephrologist and
      thus more likely to initiate their first dialysis session with a permanent
      access. Emphasis on early referral of patients with chronic kidney disease
      without diabetes to nephrologists may increase fistula use among incident
      hemodialysis patients.

PMID- 15168381
TI  - High dialysis dose is associated with lower mortality among women but not among
      men.
AB  - BACKGROUND: Several observational studies reported lower mortality risk among
      hemodialysis patients treated with doses greater than the standard dose. The
      present study evaluates, with observational data, the secondary randomized
      Hemodialysis (HEMO) Study finding that greater dialysis dose may benefit women,
      but not men. METHODS: Data from 74,120 US hemodialysis patients starting end
      stage renal disease therapy were analyzed. Patients were classified into 1 of 5
      categories of hemodialysis dose according to their average urea reduction ratio
      (URR), and their relative risk (RR) for mortality was evaluated by using Cox
      proportional hazards models. Similar analyses using equilibrated Kt/V were
      completed for 10,816 hemodialysis patients in the Dialysis Outcomes and Practice
      Patterns Study (DOPPS) in 7 countries. RESULTS: For both men and women, RR was
      substantially lower in the URR 70%-to-75% category compared with the URR 65%-to
      70% category. Among women, RR in the URR greater-than-75% category was
      significantly lower compared with the URR 70%-to-75% group (P < 0.0001); however,
      no further association with mortality risk was observed for the greater-than-75%
      category among men (P = 0.22). RR associated with doses greater than the Kidney
      Disease Outcomes Quality Initiative guidelines (URR > or = 65%) was significantly
      different for men compared with women (P < 0.01). Similar differences by sex were
      observed in DOPPS analyses. CONCLUSION: The agreement of these observational
      studies with the HEMO Study supports the existence of a survival benefit from
      greater dialysis doses for women, but not for men. Responses to greater dialysis
      dose by sex deserve additional study to explain these differences.

PMID- 15168382
TI  - Ultrapure dialysate decreases plasma pentosidine, a marker of "carbonyl stress".
AB  - BACKGROUND: Advanced glycation end products (AGEs) and their reactive carbonyl
      precursors accumulate in renal failure ("carbonyl stress"). Carbonyl stress
      derives from a broad derangement in the nonenzymatic biochemistry of both
      carbohydrates and lipids. We tested the influence of dialysate quality on plasma
      level of pentosidine, an AGE moiety taken as a surrogate marker of carbonyl
      stress, in hemodialysis patients. METHODS: Plasma pentosidine is measured by
      means of high-performance liquid chromatography in patients hemodialyzed
      successively with a conventional and an ultrapure endotoxin-free dialysate.
      RESULTS: Dialysate endotoxin level decreased from 0.040 +/- 0.017 EU/mL before
      the switch to the new water supply system to less than the detection limit
      (<0.001 EU/mL) after the switch. Plasma pentosidine levels decreased from 1.55 +/
      0.61 nmol/mL before the switch to 1.38 +/- 0.52 nmol/mL (P < 0.0001) and 1.31 +/
      0.50 nmol/mL (P < 0.0001) 3 and 6 months after the switch to an ultrapure
      dialysate, respectively. Decreases in plasma pentosidine levels were similar
      regardless of dialyzer membrane type; ie, high-flux polysulfone, high-flux
      polymethylmethacrylate, and low-flux cellulose acetate membranes. Unexpectedly,
      plasma triglyceride levels decreased from 150 +/- 116 mg/dL (1.69 +/- 1.31
      mmol/L) before the switch to 124 +/- 79 mg/dL (1.40 +/- 0.89 mmol/L; P < 0.01)
      and 119 +/- 75 mg/dL (1.34 +/- 0.85 mmol/L; P < 0.01) 3 and 6 months after the
      switch despite unchanged total cholesterol levels, respectively. Changes in
      pentosidine levels were unrelated to those in triglycerides, and both were
      unrelated to C-reactive protein levels, which remained stable throughout the
      study. CONCLUSION: Ultrapure dialysate reduces plasma pentosidine levels and
      improves plasma triglyceride levels in hemodialysis patients through still
      undefined mechanisms.

PMID- 15168383
TI  - Defective regulation of iron transporters leading to iron excess in the
      polymorphonuclear leukocytes of patients on maintenance hemodialysis.
AB  - BACKGROUND: Although hemodialysis (HD) patients are suspected of having
      defectively regulated iron metabolism, intracellular iron status has never been
      investigated thoroughly. To clarify the iron metabolism of HD patients, proteins
      involved in iron import (transferrin receptor [TfR]), as well as export
      (ferroportin 1), were investigated in polymorphonuclear leukocytes (PMNLs).
      Relations between iron status and several PMNL functions also were tested.
      METHODS: Seventeen HD patients and 17 controls were recruited. Relative
      quantitative polymerase chain reaction was used to measure ferroportin 1 and TfR
      messenger RNA (mRNA), and ferroportin 1 and TfR expression were semiquantified by
      means of Western blot analysis or immunohistochemistry. PMNL functions also were
      examined. RESULTS: Serum iron levels were significantly lower in HD patients than
      controls, and serum ferritin levels, as well as PMNL ferritin and iron content,
      were elevated in HD patients. Ferroportin 1 mRNA levels were substantially lower
      in PMNLs from HD patients, whereas TfR mRNA levels were higher. Western blot
      analysis and immunohistochemistry confirmed that expression of the corresponding
      proteins paralleled those of the mRNAs. PMNL phagocytic and bactericidal activity
      did not differ between HD patients and controls. Chemotactic peptide f-Met-Leu
      Phe-stimulated degranulation activity of lactoferrin (Lf) was decreased
      significantly in HD patients, whereas those of myeloperoxidase and elastase were
      accelerated. Lf release correlated negatively with intracellular ferritin level.
      CONCLUSION: We show for the first time that increased iron levels in PMNLs of HD
      patients were associated with downregulation of ferroportin 1 and upregulation of
      TfR, which might be linked to hypercytokinemia.

PMID- 15168384
TI  - Evaluating preload dependence of a novel Doppler application in assessment of
      left ventricular diastolic function during hemodialysis.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction, commonly found in
      hemodialysis (HD) patients, is a major cause of intradialytic hypotension.
      Conventional Doppler interrogation of mitral flow velocities typically is load
      dependent. Tissue Doppler imaging (TDI) recently was proposed as a new and
      relatively load-independent approach to assess diastolic function. The aim of
      this study is to determine whether HD-related volume reduction affects mitral
      annular velocities in a large number of patients. METHODS: One hundred twenty
      eight uremic patients underwent Doppler echocardiography 1 hour before and after
      HD. Two-dimensional and M-mode echocardiography were used to analyze LV size,
      volume, mass, systolic function, and the inferior vena cava. Doppler signals were
      obtained from the mitral inflow and TDI of the mitral annulus to measure
      variations in hemodynamics and LV diastolic filling parameters. RESULTS: After
      HD, LV size, volume, mass, stroke volume, and cardiac output were significantly
      decreased (all P < 0.001). Peak early (E) and late diastolic velocities (A) and
      E/A ratio decreased significantly after HD (all P < 0.001). Mitral annulus E'
      velocity and E'/A' ratio also changed significantly (both P < 0.001), whereas A'
      did not. Consequently, changes in E and A significantly differed with respect to
      the varying amount of ultrafiltration (both P < 0.05). CONCLUSION: Our larger
      cohort study shows that the proposed technique of TDI is still volume dependent.
      Therefore, LV diastolic function in HD patients must be assessed carefully in a
      timely manner, even when the new Doppler application is used.

PMID- 15168385
TI  - Adiponectin in peritoneal dialysis patients: a comparison with hemodialysis
      patients and subjects with normal renal function.
AB  - BACKGROUND: Adiponectin, a cytokine with anti-inflammatory properties that is
      secreted from adipose tissue, is associated with insulin resistance. Adiponectin
      has been shown to be a predictor of cardiovascular events in both the general
      population and patients undergoing hemodialysis (HD); however, its role in
      peritoneal dialysis (PD) analogues remains unclear. METHODS: Serum adiponectin
      levels, measured by means of enzyme-linked immunosorbent assay in subjects with
      normal renal function and patients undergoing HD or PD (28 subjects in each
      group), were analyzed to establish the relationship between adiponectin and lipid
      levels, as well as insulin resistance. In the second study, 104 PD patients were
      recruited to analyze the relationships between serum adiponectin level and
      residual renal and peritoneal function and C-reactive protein (CRP) level.
      Independent factors for serum adiponectin level were determined from multiple
      linear regression. RESULTS: No significant difference was shown comparing serum
      adiponectin levels of PD and HD patients; however, both were significantly
      greater than those of control subjects (P < 0.01). Negative associations were
      shown between adiponectin and triglyceride (TG; P < 0.01) and insulin levels (P <
      0.05) and homeostatic model assessment of insulin resistance (P < 0.01) for the
      former 2 groups; however, a positive association was shown for high-density
      lipoprotein (HDL) level (P < 0.05). Neither HD nor PD removed adiponectin
      significantly, with levels for the PD group negatively associated with residual
      renal function (P < 0.01) and CRP level (P < 0.001). PD patients administered
      glucose-lowering agents had lower adiponectin levels; however, lipid-lowering
      agents and renin-angiotensin blockades did not appear to affect them. Independent
      determinants for serum adiponectin level in PD patients were TG, HDL, and CRP
      levels and body mass index, after adjustment for age, sex, PD therapy duration,
      and diabetes. Adiponectin levels were not associated with left ventricular mass
      or ejection fraction. As for HD patients, PD patients had high adiponectin
      levels; adiponectin was not removed effectively using either of the studied
      dialysis modalities. In addition to a significant relationship with the
      components of insulin resistance, adiponectin level was associated with CRP level
      in these patients. CONCLUSION: These results indicate that adiponectin level in
      PD patients may be a good indicator of cardiovascular disease risk.

PMID- 15168387
TI  - The effect of ACE inhibitor and angiotensin II blocker therapy on early
      posttransplant kidney graft function.
AB  - BACKGROUND: It is unknown whether continuation of angiotensin-converting enzyme
      (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney
      transplantation has an influence on early kidney graft function. METHODS: We
      compared early postoperative graft function between 260 cadaveric kidney
      transplant recipients, either with or without peritransplantation ACE
      inhibitor/ATII blocker therapy. Regression analysis was used to show the
      influence of variables interfering with posttransplantation serum creatinine
      levels. The effect of different variables on the occurrence of delayed graft
      function (DGF) was analyzed by means of stepwise logistic regression. Improvement
      in kidney function during the first week after transplantation was compared
      between groups by means of Kaplan-Meier survival analysis. RESULTS: Intake of an
      ACE inhibitor or ATII blocker did not influence immediate posttransplantation
      graft function or the occurrence of DGF. Conversely, serum creatinine levels
      decreased significantly faster in patients administered an ACE inhibitor/ATII
      blocker than in those without therapy (P < 0.01). The only variables delaying
      graft function were number of previous transplantations, cold ischemia time, and
      male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy
      had significantly faster graft recovery (P < 0.001). CONCLUSION: Our results
      suggest that intake of an ACE inhibitor or ATII blocker during the immediate
      posttransplantation course is safe and does not impair graft function.
      Additionally, patients with DGF might profit from blockade of the renin
      angiotensin-aldosterone system, which possibly shortens the time to graft
      recovery.

PMID- 15168386
TI  - Effects of an angiotensin II receptor blocker, valsartan, on residual renal
      function in patients on CAPD.
AB  - BACKGROUND: Both residual renal function and blood pressure (BP) control
      contribute to patient survival in patients receiving continuous ambulatory
      peritoneal dialysis (CAPD). It is unknown whether antihypertensive drugs affect
      residual renal function in addition to BP reduction. METHODS: We examined the
      effects of an angiotensin II receptor blocker, valsartan, on residual renal
      function and total clearance (renal and peritoneal) in 34 Japanese CAPD patients
      from 3 months to 2 years after the start of dialysis therapy. Patients were
      randomly assigned to valsartan (n = 18; age, 63.5 +/- 3.7 years; 11 men, 7 women)
      or a control group (n = 16; age, 63.5 +/- 3.3 years; 10 men, 6 women).
      Conventional antihypertensive treatment was continued in all patients to achieve
      the target BP in both groups of 130/80 mm Hg or less, measured at home. RESULTS:
      BP reduction was similar in the valsartan and control groups. Valsartan
      significantly slowed the progressive decline in both residual renal function (3.2
      +/- 0.3 to 4.3 +/- 0.7 mL/min/1.73 m2) and total clearance (42.1 +/- 3.2 to 48.3
      +/- 4.8 L/wk/1.73 m2) by dialysis in CAPD patients compared with controls (5.9 +/
      0.5 to 2.8 +/- 0.4 mL/min/1.73 m2; 47.1 +/- 4.8 to 31.4 +/- 5.2 L/wk/1.73 m2).
      CONCLUSION: This study shows that in patients with hypertension starting CAPD
      therapy, valsartan slows the decline in residual renal function and contributes
      to maintenance of weekly creatinine clearance and Kt/V (fraction per dialysis),
      which are the major factors contributing to the mortality and morbidity of CAPD
      patients. This effect appears to be mostly a result of maintaining residual renal
      function.

PMID- 15168388
TI  - Hypertension after kidney transplantation.
AB  - BACKGROUND: Few studies have examined the possible role of blood pressure (BP),
      independent of acute rejection and graft function, on outcomes after kidney
      transplantation. METHODS: We investigated the prevalence, treatment, control, and
      clinical correlates of hypertension and its association with outcomes, using
      multivariate analyses with time-dependent covariates, in a retrospective cohort
      of 1,666 kidney transplant recipients. RESULTS: Hypertension was common, and its
      control was poor. For example, at 1 year, only 55.5% had a BP less than 140 mm
      Hg. Control improved only slightly in 1993-2002 compared to 1976-2002, even as
      patients administered 2 or more antihypertensive medications at 1 year increased
      from 43.5% to 54.6%. Independent correlates of higher BP included male sex, age,
      donor age, diabetes, body mass index, the presence of native kidneys, and delayed
      graft function. Previous acute rejection was associated with higher BP at
      virtually all times after transplantation, and these associations were
      independent of estimated creatinine clearance (C(Cr)). Conversely, an association
      between BP and subsequent acute rejection was not statistically significant when
      differences in C(Cr) were taken into account. After adjusting for the effects of
      acute rejection, C(Cr), and other variables, each 10 mm Hg of systolic BP was
      associated with an increased relative risk for graft failure (1.12; 95%
      confidence interval, 1.08 to 1.15; P < 0.0001), death-censored graft failure
      (1.17; 1.12 to 1.22; P < 0.0001), and death (1.18; 1.12 to 1.23; P < 0.0001).
      CONCLUSION: High BP is closely tied to graft function, but nevertheless is an
      independent risk factor for graft failure and mortality. Better strategies are
      needed to control BP after kidney transplantation.

PMID- 15168389
TI  - The differential effect of race among pediatric kidney transplant recipients with
      focal segmental glomerulosclerosis.
AB  - BACKGROUND: Given the differential effect of race on focal segmental
      glomerulosclerosis (FSGS) progression in native kidneys, recurrence of FSGS in
      the transplanted kidney, and allograft source, the authors conducted this study
      to evaluate the influence of FSGS by race and allograft source. METHODS: Data
      from 8,065 pediatric renal transplant recipients (n = 620 FSGS) between 1987 and
      1997 from the United Network for Organ Sharing registry were used for this study.
      Stratified analysis by race and allograft source allowed independent assessment
      of the effect of FSGS on transplant survival. RESULTS: Among black children,
      allograft survival was not different between FSGS and non-FSGS patients adjusted
      for recipient age, recurrent disease, allograft source, zero antigen mismatch,
      and acute rejection (hazard ratio [HR], 1.15; 95% confidence interval [95% CI],
      0.93 to 1.42; P = 0.22). Among nonblack children, the risk of allograft failure
      in children with FSGS was 1.31 times higher than other causes of end-stage renal
      disease (ESRD) in multivariate analysis (95% CI, 1.04 to 1.64; P = 0.02). Despite
      the impact of disease recurrence in the nonblack children with FSGS, the risk of
      graft failure was less for living donor recipients (HR, 1.51; 95% CI, 1.08 to
      2.10) than for cadaveric recipients (HR, 1.80; 95% CI, 1.32 to 2.44) compared
      with the lowest risk group (nonblack, non-FSGS, living donor). CONCLUSION: The
      effect of FSGS on renal allograft survival in children differs between racial
      groups. Children of nonblack races with FSGS have a worse allograft survival rate
      compared with other causes of ESRD. Within nonblack children with FSGS, living
      donor transplants convey a better allograft survival than cadaveric transplants.

PMID- 15168390
TI  - High cumulative incidence of urinary tract transitional cell carcinoma after
      kidney transplantation in Taiwan.
AB  - BACKGROUND: Cancer is a well-documented complication after kidney
      transplantation. Increased incidence of bladder cancer had been reported in long
      term hemodialysis patients in Taiwan. Herein, the authors report a very high
      cumulative incidence of transitional cell carcinoma (TCC) of the urinary tract
      after kidney transplantation in Taiwan. METHODS: The authors retrospectively
      reviewed the clinical data, medical records, and outcome of 730 kidney transplant
      (KT) recipients. The cumulative incidence of TCC was computed. The Cox regression
      method was used to analysis the role of potential risk factors. RESULTS: After a
      mean follow-up duration of 72.2 +/- 54.4 months, 69 cancers were diagnosed in 63
      (8.6%) KT recipients. Of them, 30 cases (4.1%) were TCC. The cumulative incidence
      for TCC was 3.0% after 3 years of graft survival, increasing to 7.2% at 6 years
      and 17.5% at 10 years. Compared with the general population in Taiwan, the
      standardized mortality ratio was 398.4 (male, 192.6; female, 875.6). Painless
      gross hematuria was the cardinal initial symptom in 22 (73.3%) of the 30 KT
      recipients with TCC. Another 4 (13.3%) KT recipients with TCC presented with
      chronic urinary tract infection (UTI). Bilateral nephroureterectomy with removal
      of bladder cuffs was performed in 18 (60%) patients. Synchronous TCC in bilateral
      upper urinary tracts was confirmed in 11 (36.7%) of KT recipients with TCC. The
      age at the time of KT, female sex, compound analgesics usage, Chinese herb usage,
      and underground water intake had statistical significance as risk factors (P <
      0.05). CONCLUSIONS: The KT recipients are at extremely high risk for TCC in
      Taiwan, with an incidence of 4.1%. This study indicates that hematuria and
      chronic UTI are the initial presentation of TCC in KT recipients. Carefully
      urologic screening is indicated for patients with high risk for TCC, including
      those with older age, compound analgesics usage, Chinese herbs usage, and
      underground water intake as well as women.

PMID- 15168391
TI  - Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney
      transplant patients.
AB  - BACKGROUND: Oral administration of ferrous-sulfate was reported to decrease
      intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese
      individuals by 90%. METHODS: We examined the effect of a single oral dose of
      ferrous sulfate on steady-state mycophenolic acid pharmacokinetics in 10 iron
      deficient (hypochromic red blood cells >2.5%), Caucasian, long-term kidney graft
      recipients using a randomized, open-label, crossover design. On days A and B, MMF
      (1,000 mg) was given orally at 8:00 am. On day C, MMF and ferrous sulfate (105
      mg) were coadministered at 8:00 am. On day D, MMF was given at 8:00 am and
      ferrous sulfate was given orally 4 hours later. RESULTS: The interindividual
      variability of the 12-hour area under the plasma mycophenolic acid concentration
      versus time curves (AUC(0-12)) under control conditions was small (89.5 +/- 27.8
      and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent
      administration of MMF and ferrous sulfate did not affect the bioavailabilty of
      MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x h/L). CONCLUSION:
      Oral therapy of iron deficiency using ferrous sulfate in long-term kidney graft
      recipients does not impede intestinal absorption of MMF; hence, exposure to this
      immunosuppressive agent is not reduced.

PMID- 15168392
TI  - Successful treatment of calciphylaxis with intravenous sodium thiosulfate.
AB  - Calciphylaxis is a dreaded complication of renal failure characterized by nodular
      subcutaneous calcification and painful tissue necrosis often leading to
      ulceration, secondary infection, and high mortality rates. The case of a woman
      receiving continuous ambulatory peritoneal dialysis who had a typical clinical
      presentation of calciphylaxis confirmed by x-ray and technetium scan findings is
      described. After nonresponse to conventional therapy, treatment with intravenous
      sodium thiosulfate 3 times weekly was begun, and she had rapid and dramatic
      relief of signs and symptoms and improvement of technetium scans. Prolonged
      treatment was well tolerated without serious side effects and accompanied by
      continued clinical improvement.

PMID- 15168393
TI  - Erosion of embolization coils and guidewires from the kidney to the colon:
      delayed complication from coil and guidewire occlusion of renal arteriovenous
      malformation.
AB  - Percutaneous transarterial embolization is a useful, nondrastic, valuable, and
      commonly used therapeutic option for the treatment of renal arteriovenous
      malformation (AVM). Compared with partial or total nephrectomy, transarterial
      embolization is more conservative and preserves renal function. However, it has
      some limitations and complications that could cause renal infarction and
      progression of hypertension, renal insufficiency, and pulmonary embolism. Large
      sized AVM and multiplicity of abnormal vessels also limit the use of the
      embolization technique. The authors experienced erosion of the coils and
      guidewires that were used for embolization of renal AVM from kidney to descending
      colon. Coil embolization is practiced extensively, but a complication such as
      this does not appear to have been described.

PMID- 15168394
TI  - Blockade of the renin-angiotensin system: better late than never.

PMID- 15168395
TI  - Transplant: immunology and treatment of rejection.

PMID- 15168404
TI  - ARF with casts eliciting a cellular reaction.

PMID- 15168406
TI  - Medullary cystic kidney disease type 2.

PMID- 15168407
TI  - Normomagnesemic Gitelman's syndrome?

PMID- 15168420
TI  - tuberculous otitis media in a renal transplant recipient.
AB  - Tuberculous otitis media is a rare cause of chronic suppurative infection of the
      middle ear and a very uncommon form of extrapulmonary tuberculosis. Although
      there have been several case reports in the nonimmunosuppressive population of
      tuberculous otitis media, it has never been reported in an immunosuppressed
      allograft recipient. We present a case of diagnosed tuberculous otitis media
      after recurrent chronic otitis media treated several times with empiric
      antibiotic treatment. After the patient developed postauricular fistula and
      underwent surgical removal of granulation tissue, the diagnosis was made on the
      basis of histopathology and growth in culture of Ziehl-Neelsen. Clinical response
      promptly followed institution of antituberculous treatment including isoniazid,
      rifampicin, ethambutol, and pyrazinamide.

PMID- 15168421
TI  - Excision margins in high-risk malignant melanoma.

PMID- 15168422
TI  - Alendronate versus calcitriol for prevention of bone loss after cardiac
      transplantation.

PMID- 15168423
TI  - Alendronate versus calcitriol for prevention of bone loss after cardiac
      transplantation.

PMID- 15168424
TI  - Predicting outcomes in chronic obstructive pulmonary disease.

PMID- 15168425
TI  - Predicting outcomes in chronic obstructive pulmonary disease.

PMID- 15168426
TI  - Predicting outcomes in chronic obstructive pulmonary disease.

PMID- 15168427
TI  - Identity, place, and bystander intervention: social categories and helping after
      natural disasters.
AB  - The authors developed a Self-Categorization Theory (SCT) approach to bystander
      behavior. Participants were 100 undergraduates at an English university. The
      authors made either a European or a British identity salient. Participants then
      rated their likelihood of offering both financial and political help after
      natural disasters in Europe and South America. When European (but not British)
      identity was salient, participants were less likely to offer help for disasters
      in South America than Europe. They were also more likely to offer financial help
      after disasters in Europe when European non-British identity was salient. There
      were no differences in levels of emotional response to disasters by identity
      salience. Results indicate that social category relations rather than
      geographical proximity or emotional reaction are most important in increasing
      helping behavior after natural disasters.

PMID- 15168428
TI  - Disconfirming intergroup evaluations: asymmetric effects for in-groups and out
      groups.
AB  - The authors examined whether a fundamental bias in the way people process
      information has implications for efforts to improve intergroup relations. The
      authors exposed participants to information about their own social category and a
      different social category that was either positive or negative in connotation. To
      examine what effect this information would have on participants' attitudes toward
      their own group and the other group, the authors measured both explicit and
      implicit evaluations before and after exposure. The findings suggest that, at a
      preconscious level, exposure to negative information affects participants'
      attitudes toward their own group, but that positive information has a negligible
      impact on attitudes toward other groups. The authors found an opposite pattern
      for explicit (conscious) evaluations. These asymmetries are consistent with
      cognitive and motivational theory on intergroup relations and may have important
      implications for efforts to reduce prejudice.

PMID- 15168429
TI  - The conflicting standards dilemma and gender: a mediating model of its affective
      implications and coping styles.
AB  - Women face both traditional and nontraditional standards for gender-appropriate
      behavior, and society values neither set of standards wholly. In the present
      study, the author defined this paradox as the Conflicting Standards Dilemma
      (CSD). Female participants (N = 255) provided descriptions of the levels of
      femininity and masculinity expected of them by 3 specific others (mother, father,
      partner) and 3 generalized others (men, women, society), completed a mood
      questionnaire, and completed a scale assessing 4 proposed coping styles. The
      results supported the existence of a CSD and partially supported an hypothesized
      association with negative affect. The author also found support for a mediational
      model in which coping style mediated the emotional impact of conflicting
      standards. The results indicated that societal expectations of women are complex
      and contradictory, and that this situation has a negative impact on women who
      have not developed adaptive coping styles.

PMID- 15168430
TI  - Citizenship behavior at the team level of analysis: the effects of team
      leadership, team commitment, perceived team support, and team size.
AB  - The authors investigated citizenship behavior at the team level of analysis by
      examining 71 change management teams, teams that are responsible for implementing
      organizational change. The authors collected data at an automotive-industry firm
      in the mid-Atlantic United States using a questionnaire methodology and an
      examination of company records. Team leader behavior, team commitment, and
      perceived team support all had large effects on team citizenship behavior,
      whereas team size had a small-to-negligible effect.

PMID- 15168431
TI  - Trust in the workplace: factors affecting trust formation between team members.
AB  - The authors used survey data from 127 professional-level employees working in 8
      industries to assess the effects of respondent's trusting stance and (a) the
      trustee's organization membership (internal or external), (b) the hierarchical
      relationship (supervisor or peer), and (c) the gender of the trustee, on initial
      trust level for a new project team member. The authors found that trusting stance
      was positively related to initial trust level. The authors also found an
      interaction effect between respondent gender and trustee gender on initial trust.
      Specifically, male initial trust level was higher for a new male team member and
      lower for a new female team member. The present study provided additional
      understanding of the formation of initial trust levels and its importance for
      team functioning.

PMID- 15168432
TI  - Rated importance of personal qualities across four relationships.
AB  - Are there stable personal qualities that people value in others across a range of
      personal and professional relationships? For 4 relationship types that varied
      across social and professional associations (those of "close friend," "romantic
      partner," "an employee of yours," and "your boss"), participants rated each of 34
      personal qualities on the basis of how important it would be in selecting someone
      for the relationship. The author factor-analyzed the ratings of importance and
      created composite scores to represent the 4 factors identified (intimacy,
      dependability, achievement, and kindness). The author found no difference that
      was due to relationship type for the factor of kindness. The relationship of
      romantic partners received the highest ratings on the factor of intimacy.
      Participants rated the relationship of close friends lower than the other 3
      relationships for both of the factors of dependability and achievement. The
      results indicated that people value some qualities the same regardless of the
      relationship involved, with other qualities varying in importance across these
      relationships. Of special interest was the tendency of participants to see stable
      qualities as generally less important for choosing close friends than for
      choosing the others in the other three relationships.

PMID- 15168434
TI  - A psychometric examination of the personal attributes questionnaire.

PMID- 15168433
TI  - Implicit bias and contact: the role of interethnic friendships.
AB  - In 2 studies, the authors examined the role of interethnic friendship with
      African Americans or Latinos in predicting implicit and explicit biases against
      these groups. White participants completed the Implicit Association Test (IAT;
      Greenwald, A. G., McGhee, D. E., & Schwartz, J. L. K., 1998), several self-report
      bias measures, and a friendship questionnaire. Participants with close friends
      who were members of the target group exhibited less implicit prejudice than
      participants without close friends from the target group. Friendship influenced
      only 2 of the 7 explicit measures, a result that likely stems from social
      desirability bias rather than truly non-prejudiced attitudes. Results support the
      importance of contact, particularly interethnic friendship, in improving
      intergroup attitudes.

PMID- 15168435
TI  - [Diagnosis and treatment of tuberculous pleurisy--with special reference to the
      significance of measurement of pleural fluid cytokines].
AB  - Tuberculous pleurisy as well as malignant pleuritis is a representative disease
      presenting pleural effusion. The diagnosis of tuberculous pleurisy is made from
      examination of pleural effusion, but the sensitivity of smear or culture of
      Mycobacterium tuberculosis from pleural fluid is generally low. Although the
      pleural fluid concentration of adenosine deaminase (ADA) is useful in terms of
      sensitivity or specificity, the value could be high in empyema or rheumatoid
      pleuritis. Thoracoscopic biopsy of pleura is more sensitive rather than
      conventional percutaneous needle biopsy, but is more invasive. Tuberculous
      pleural effusion is caused by delayed allergy which macrophage and T-helper 1
      cells mainly relate and the stimuli of bacterial body consecutively induces T
      helper 1 cytokines. Pleural fluid interferon-gamma (INF-gamma) is important not
      only in pathogenesis but also in diagnosis. We demonstrated that INF-gamma is a
      more sensitive and specific indicator for tuberculous pleurisy than ADA using
      receiver operating characteristics (ROC) analysis. Cytometric bead array (CBA) is
      a tool to simultaneously measure abundance of various cytokines and is expected
      to be a very useful method to provide informations for understanding a feedback
      mechanism of cytokine network. It is needed to clear the immunity in pleural
      fluid and to establish the less invasive and more useful method to diagnose
      tuberculous pleurisy.

PMID- 15168436
TI  - [The clinical features of ultra-old tuberculosis patients in our hospital].
AB  - PURPOSE: To examine the clinical features of ultra-old patients over 85 years of
      age who were admitted to our hospital for tuberculosis treatment. METHODS:
      Clinical features of tuberculosis patients over 85 years of age who were admitted
      to our hospital from January, 1996 to May, 2003 were analyzed in relation to
      their disease status, complications and prognosis. RESULTS: They showed a high
      tuberculin negative rate (26.2%) and a low rate of cavity formation (21.8%), and
      the smear positive rate of tubercle bacilli was not high (51.2%). As to the
      complications, cerebrovascular disorders were overwhelmingly high (62.2%) and the
      death rate due to side effects of drugs was high. The sputum smear positive rate
      was higher (70%) among patients from nursing home. CONCLUSION: The diagnosis of
      tuberculosis was often delayed with high mortality rate due to side effects of
      drugs among ultra-old patients and tuberculosis infection control measures to
      contacts are often needed.

PMID- 15168437
TI  - [Thoracic malignancies in patients with chronic tuberculous empyema].
AB  - OBJECTIVES: To clarify features of thoracic malignancies occurred in patients
      with chronic tuberculous empyema. MATERIALS AND METHODS: We analyzed
      clinicopathological data of 15 patients with thoracic malignancies who had
      chronic tuberculous empyema, encountered at Tokyo National Hospital during the
      period from 1977 to 2002. RESULTS: There were 13 men and 2 women, with a mean age
      of 67 years. Most of all (13/15) patients had history of surgery for tuberculosis
      including artificial pneumothorax (9 cases). Malignancies consisted of pyothorax
      associated lymphoma (PAL; 9 cases), lung cancer (4 cases), malignant fibrous
      histiocytoma (1 case), and angiosarcoma (1 case). There were no differences in
      background factors between PAL patients and the other patients. Common symptoms
      were chest pain (10 cases), fever (7 cases), and bloody sputum (4 cases) and it
      seemed that these symptoms were more evident in patients with PAL than in
      patients with other diseases. Plain chest X-ray films often failed to detect the
      tumor, and the diagnosis was often obtained by sputum cytology,
      bronchofiberscopy, transcutaneous biopsy, and resection with support of CT and/or
      MRI films. On radiographs, all tumors located in empyema cavities or around
      empyema walls, and a pulmonary mass adjacent to the empyema wall was
      characteristic of lung cancer. PAL showed certainly good outcome; 40% 5-year
      survival rate with resection or chemoradiotherapy. On the other hand, all of lung
      cancer cases were diagnosed at stage III, and had poor outcome, and the remaining
      patients with the other malignancies also had poor outcome. CONCLUSION:
      Clinicians should keep in mind occurrence of several thoracic malignancies during
      the follow-up of patients with chronic tuberculous empyema.

PMID- 15168438
TI  - [C-reactive protein in patients with bacteriological positive lung tuberculosis].
AB  - PURPOSE: To investigate the usefulness of measuring C-reactive protein in the
      diagnosis of lung tuberculosis. OBJECT: Tuberculosis patients treated by
      chemotherapy at Fukujuji Hospital from Jan./1/2000 to Dec./31/2001. METHOD: Chart
      review. RESULTS: CRP are negative in 13.3% (95%CI: 8.9-17.7%) in sputum smear
      positive lung tuberculosis patients (N = 226), and in 73.0% (95%CI: 62.0-84.0%)
      of sputum smear negative culture positive lung tuberculosis patients (N = 63).
      CONCLUSION: Usefulness of measuring C-reactive protein in the diagnosis of
      bacteriological positive lung tuberculosis is limited.

PMID- 15168440
TI  - [Overview of FAB/WHO classification and therapeutic modalities for
      myelodysplastic syndromes].

PMID- 15168439
TI  - [Four cases of Mycobacterium xenopi pulmonary disease].
AB  - Mycobacterium xenopi is very rare pathogen in Japan. We reported herein four
      cases of M. xenopi pulmonary disease. These patients were all male and their ages
      ranged from 53 to 72. They all had past history of pulmonary tuberculosis,
      including two cases who had been also treated for Mycobacterium kansasii
      pulmonary disease later. The bacilli could be cultured in Mycobacteria Growth
      Indicator Tube (MGIT) system from 10 sputum samples, but they could not be
      cultured on Ogawa egg media except for two samples. All four cases fulfilled the
      criteria for the diagnosis of nontuberculous mycobacteria pulmonary disease
      proposed by the Japanese Society for Tuberculosis. Combination chemotherapy
      including isoniazid, rifampicin, and ethambutol was started in all four cases
      when mycobacteria were detected under tentative diagnosis of the relapse of
      tuberculosis or Mycobacterium kansasii disease. Sputum converted to culture
      negative by the chemotherapy in two cases. In one case, the chemotherapeutic
      regimen was changed to rifampicin, ethambutol, and clarithromycin after the
      bacteriological identification of M. xenopi, and the new regimen was found to be
      effective. In the final case, both of the regimens were finally ineffective.

PMID- 15168442
TI  - [Immunosuppressive therapy for low-risk MDS: markers for good response].

PMID- 15168441
TI  - [Refractory anemia (RA) and refractory cytopenia with multilineage dysplasia
      (RCMD) in WHO classification: comparison between Japanese and German cases].

PMID- 15168443
TI  - [Chemotherapy regimens for high-risk myelodysplastic syndromes: what is your
      decision?].

PMID- 15168444
TI  - [Molecular pathogenesis and treatment of AML].

PMID- 15168445
TI  - [Prevention of hepatic veno-occlusive disease by a combination of heparin and
      prostaglandin E1 in children undergoing hematopoietic stem cell transplantation].
AB  - The effect and safety of combination prophylaxis for hepatic veno-occlusive
      disease (VOD) following stem cell transplantation (SCT) was retrospectively
      evaluated in a total of 53 children who survived until day 30. Prophylaxis was
      started on the day before conditioning, and heparin (10 unit/kg/hr) alone was
      used in 6 patients, PGE1 (5 ng/kg/min) plus heparin plus PTX (200 mg/day) in 17
      patients, lipo-PGE1 (0.5 ng/kg/min) plus heparin plus PTX in 7 patients, and lipo
      PGE1 plus heparin in 23 patients. Diagnosis of VOD was made based on McDonald's
      criteria in 5 cases (9.4%), but not on Jones' criteria. No statistically
      significant difference was observed in the incidence of VOD among each
      prophylaxis group. The degree of VOD was mild in all of 5 cases, and all
      recovered with continuation of the prophylactic procedure. Each prophylactic
      procedure was performed without any significant adverse effect except for seizure
      induced by lipo-PGE1 in one patient with Lennox syndrome. Since both the
      incidence and fatality rate of VOD in children undergoing SCT are approximately
      20% according to most of the previous reports, the present study suggests the
      effectiveness of combination prophylaxis.

PMID- 15168446
TI  - [Diffuse large B-cell lymphoma of the knee occurring 70 years after tuberculous
      arthritis].
AB  - A 72-year-old woman presented with a progressive swollen and painful left knee
      over a period of a month. The patient had a history of tuberculous arthritis of
      the left knee joint at the age of 1-2 years. Since then the knee showed a
      deformity and contraction. MRI scan demonstrated a soft tissue tumor measuring 7
      x 8 x 6 cm in the front of the knee, a biopsy specimen taken from which revealed
      large B-cell lymphoma. The tumor cells showed a phenotype of CD3- CD5- CD10-
      CD20+ CD21- BCL2+, and surface immunoglobulin M-kappa. Since the lymphoma cells
      were found to be negative for Epstein-Barr virus encoded RNA by means of in situ
      hybridization, the DLBCL in this patient was thought to be caused by a different
      mechanism from pyothorax-associated lymphoma. The patient was treated with
      chemotherapy (CHOP) followed by radiotherapy, and obtained partial remission.
      There is no evidence of progression seven months after diagnosis.

PMID- 15168447
TI  - [Non-myeloablative stem cell transplantation from an HLA identical sibling donor
      in a case of treatment-related acute myelogenous leukemia].
AB  - A 50-year-old man was admitted to our hospital because of thrombocytopenia during
      a follow up study of diffuse large B-cell lymphoma in second complete remission.
      He was diagnosed as having therapy-related acute myelgenous leukemia (t-AML) on
      the basis of the bone marrow findings and his chemotherapeutic agent history
      including alkylating agents. Complete remission was achieved by induction
      chemotherapy. Although allogeneic stem cell transplantation was thought to be
      needed, the patient was thought to be ineligible for any myeloablative
      conditioning regimen because of his age and the history of long term
      chemoradiotherapy. A non-myeloblative regimen was thus selected. After
      preconditioning with fludarabine, cyclophosphamide and cytarabine, the patient
      underwent peripheral blood stem cell transplantation from an HLA identical
      sibling donor. Complete donor chimeras were obtained on day 28 after
      transplantation. Regimen related toxicities over grade 2 were not observed.
      Although he suffered from mild chronic graft-versus-host disease(GVHD), he is in
      good condition without any signs of relapse during a follow-up period of 33
      months. It is suggested that non-myeloablative transplantation is feasible and
      benefical for patients with t-AML who are often ineligible for myeloablative
      transplants because of their histories of long term chemoradiotherapies.

PMID- 15168448
TI  - [A hairy B cell lymphoproliferative disorder resembling hairy cell leukemia].
AB  - This case report describes a hairy B cell lymphoproliferative disorder (HBLD)
      with clinical and hematological features resembling hairy cell leukemia. The
      patient was a 29-year-old female who demonstrated atypical lymphocytes in her
      peripheral blood. Physical examination demonstrated splenomegaly, but there were
      no palpable superficial lymph nodes. Hematological examination showed a leukocyte
      count of 10.6 x 10(3)/mm3 with 41% atypical lymphocytes. Bone marrow examination
      showed a normal cellular and an atypical lymphocyte count of 42%. The atypical
      lymphocytes had microvilli and prominent membranous ruffles on their surfaces.
      Atypical lymphocytes expressed CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- on the
      surface of the cells on examination by with a fluorescence activated cell sorter.
      Although these findings were similar to hairy cell leukemia, Japanese variant,
      the surface marker of the kappa chain and lambda chain was unbiased and studies
      of immunoglobulin gene rearrangements and expression showed polyclonal
      proliferation of B cells. Therefore, we diagnosed this patient as having HBLD.
      Because she did not demonstrate anemia or thrombocytopenia, she is not currently
      receiving medication. To date, the atypical lymphocyte count has not changed.

PMID- 15168449
TI  - [Adult-onset Still disease presenting with disseminated intravascular
      coagulation].
AB  - A 17-year-old female was admitted to our hospital because of pyrexia and
      thrombocytopenia in May 2002. Laboratory examination showed a platelet count of
      50,000/microliter with an increased level of fibrinogen degradation product,
      leading to a diagnosis of disseminated intravascular coagulation (DIC). Gabexate
      mesilate was intravenously administrated without any effects. Several days later,
      erythema, joint pain and neck lymphadenopathy developed sequentially. The patient
      was diagnosed as having adult-onset Still disease (AOSD) complicated with DIC.
      Moreover, serum inflammatory cytokine levels had increased and activated
      macrophages were observed in the bone marrow, suggesting the presence of
      macrophage activation syndrome. After additional treatments with dalteparin and
      aspirin, the clinical symptoms and laboratory findings associated with AOSD and
      DIC disappeared. Although this was a severe case of AOSD associated with
      preceding DIC, the AOSD symptoms resolved in this patient with the treatment of
      the DIC and with aspirin only without any relapse.

PMID- 15168450
TI  - [Early onset invasive pulmonary zygomycosis following allogeneic peripheral blood
      stem cell transplantation in a patient with therapy-related myelodysplastic
      syndrome].
AB  - A 39-year-old woman received an allogeneic peripheral blood stem cell
      transplantation from her daughter for secondary myelodysplastic syndrome. On day
      +12, a cough and fever developed. Chest X-ray and computed tomography
      demonstrated a consolidation in the left lung. A diagnosis of pulmonary
      zygomycosis was made on the histology from a transbronchial lung biopsy. Although
      amphotericin B (AMPH-B) showed efficacy, dose reduction was necessary because of
      renal toxicity. The patient died of pulmonary zygomycosis, confirmed by an
      autopsy. We strongly hope for authorization as soon as possible of the use of
      such a drug as liposomal AMPH-B which appears less toxic.

PMID- 15168451
TI  - A message to the Journal of the Physiological Society of Japan.

PMID- 15168452
TI  - [Lung cancer: molecular targeting therapy].

PMID- 15168453
TI  - [Molecular biology of lung cancer].

PMID- 15168454
TI  - [Progress of diagnostic radiology in lung cancer].

PMID- 15168455
TI  - [Chemotherapy for non-small cell lung cancer].

PMID- 15168456
TI  - [Chemotherapy for small cell lung cancer].

PMID- 15168457
TI  - [A case of eosinophilic pneumonia possibly associated with 5-aminosalicylic acid
      (5-ASA)].
AB  - A 30-year-old man was diagnosed as having ulcerative colitis and was treated with
      2,250 mg/day of 5-aminosalicylic acid (5-ASA). After 4 weeks of the
      administration, the patient complained of cough and fever and was admitted to our
      hospital. His chest radiograph showed infiltrative shadows bilaterally in the
      lung fields. Peripheral blood analysis indicated eosinophilia. We confirmed
      eosinophilic pneumonia by bronchoalveolar lavage and transbronchial lung biopsy.
      Improvement in clinical symptoms and radiological findings was obtained after the
      cessation of 5-ASA and initiation of prednisolone. Finally, mesalazine-induced
      eosinophilic pneumonia was diagnosed on the basis of his clinical course. The
      literature contains a few reports on patients with mesalazine-induced
      eosinophilic pneumonia.

PMID- 15168459
TI  - [A case of gastric cancer initially presented by bilateral chylothorax].
AB  - The patient, a 66-year-old woman, visited our hospital with chief complaints of
      nocturnal coughing and dyspnea. Chest radiography revealed bilateral pleural
      effusion, and she was admitted to our hospital to undergo more thorough
      examination. The bilateral pleural effusion was identified as chyle. In
      cytodiagnosis, a number of poorly-differentiated adenocarcinoma cells in clumps
      were detected, and mucus was found in the cell bodies. The case was diagnosed as
      signet-ring cell carcinoma. Endoscopy of the upper digestive tract was performed
      for close examination of the primary lesion. As a result, a IIc lesion
      accompanied with concentrated folds and hypertrophy was found on the anterior
      wall of the body of the stomach. Biopsy of this site led to a diagnosis of signet
      ring cell carcinoma, and these results were consistent with the cytodiagnostic
      findings of pleural effusion. Because gastric carcinoma associated with bilateral
      chylothorax is very rare in Japan, we report the results of our study with some
      discussions based on a review of the literature.

PMID- 15168458
TI  - [A case of adenocarcinoma of the lung presenting symptoms of choroidal metastasis
      as the initial clinical manifestation].
AB  - A 51-year-old woman was referred to our hospital with a complaint of disturbance
      in vision. Ophthalmologic examination revealed multiple choroidal tumors. High
      resolution CT showed a nodular shadow in the left lower lobe. Transbronchial
      biopsy and right supraclavicular lymph node biopsy specimens showed a poorly
      differentiated adenocarcinoma. We concluded that the choroidal tumors had
      metastasized from the lung. Combined chemotherapy (CDDP + CPT-11) followed by
      irradiation of both eyes and brain were performed. Nevertheless, she died 6
      months after the initial presentation. It is important to notice ophthalmologic
      symptoms because lung cancer may metastasize to the choroids.

PMID- 15168460
TI  - [A case of primary pulmonary leiomyosarcoma with history of pneumonia 5 years
      before].
AB  - A 35-year-old woman with past history of pneumonia in the right lung field 5
      years before was admitted to our hospital because of fever and cough. Chest
      radiographs showed a pulmonary tumor with atelectasis of the right lower lung.
      Chest CT also revealed a round clear-edged tumor at the right S6 with atelectasis
      of the right lower lung lobe. Bronchoscopic findings showed a yellowish
      endobronchial tumor in the right truncus intermedius, which proved to be
      leiomyosarcoma. We could not find any other malignant lesion, and therefore, on a
      diagnosis of primary pulmonary leiomyosarcoma, right middle and lower lobectomy
      was performed with lymph node excision. Retrospective examination of the chest
      radiographs revealed not only that the original region of the leiomyosarcoma
      seemed to be near the site of the earlier pneumonia, but also that the
      atelectasis-like findings 2 years before were similar to the findings on this
      admission. It was reported that, if an operation could not be performed at an
      early stage, the prognosis might be poor. In the follow-up of the abnormal chest
      radiographic findings, the clinic physician should observe the symptoms from the
      same viewpoint as hospital doctors. It is important to keep an active
      relationship between clinic and hospital. We might have reached our final
      diagnosis earlier if we had been more active in seeking an examination for
      abnormal chest radiographic findings, without attaching too much importance to
      the patient's age.

PMID- 15168461
TI  - [A case of M. fortuitum lung disease with small-cell lung cancer].
AB  - A 58-year-old man was admitted to our hospital because of an abnormal shadow
      found on chest radiography. Chest radiographs and chest CT on admission showed a
      bulla with a niveau and infiltration in the right upper lobe. Smear of sputum and
      bronchial lavage were negative for acid-fast bacilli. Despite treatment with
      meropenem and clindamycin, the infiltrating shadow worsened. Since bronchial
      lavage and sputum culture were positive for M. fortuitum, these drugs were
      replaced with minocycline and imipenem. Thereafter, the shadow on the chest
      radiograph improved. After discharge, outpatient treatment with clarithromycin
      and levofloxacin was continued. After 4 months, the residual tumor shadow in the
      right upper lobe gradually grew. When a CT-guided transcutaneous needle lung
      biopsy was undertaken, malignant cells were found. Right upper lobectomy was
      performed. Pathological examination of the lesion demonstrated small-cell lung
      cancer. If a lesion does not change after nontuberculous mycobacteria treatment,
      the physician should consider other lesions such as lung cancer.

PMID- 15168462
TI  - [A case of amyopathic dermatomyositis with interstitial pneumonia: successful
      treatment with a combination of prednisolone and cyclosporin A].
AB  - A 53-year-old woman visited our hospital in July 2002 with complaints of skin
      eruptions on the face and extremities, dry cough and dyspnea. A diagnosis of
      amyopathic dermatomyositis (ADM) was made on the basis of characteristic skin
      lesions and skin biopsy findings with slight muscle symptoms and mild elevation
      of muscle enzymes. Interstitial shadows were observed in both lower lung fields
      on chest radiographs, and thoracoscopic lung biopsy specimens revealed a diffuse
      alveolar damage (DAD) pattern. After induction of chemotherapy with prednisolone
      (50 mg/day) and cyclosporin A (150 mg/day), the respiratory symptoms and
      interstitial shadows were gradually reduced. Although it is known that
      interstitial pneumonia has an acute course and poor prognosis in ADM, the present
      case responded well to the chemotherapy with prednisolone and cyclosporin A.

PMID- 15168463
TI  - [A case of lung cancer with hereditary angioedema treated effectively by chemo
      radiotherapy with C1 esterase inhibitor concentrate and danazol].
AB  - Lung cancer with hereditary angioedema was diagnosed in a 69-year-old man.
      Laboratory examinations revealed depletion of the fourth component of complement
      and C1 inhibitor activity. A bone metastasis was present. After the first
      chemotherapy, acute attacks of edema in the upper chest and the laryngeal mucosa
      occurred and dyspnea progressed, but these symptoms were immediately improved by
      administration of C1 inhibitor concentrate. Because of the danger of angioedema
      that might be expected following chemo-radiotherapy, he was treated with danazol.
      The patient then showed no sign of an edema attack during therapy for lung
      cancer.

PMID- 15168464
TI  - [A case of infected bulla caused by Mycobacterium kansasii].
AB  - A 62-year-old man was referred to our hospital because of persistent sub-fever. A
      pulmonary fungal infection was suspected owing to the elevation of the serum-D
      glucan level. Since a chest radiograph and a CT scan revealed intrabullous fluid
      in the right upper lobe, percutaneous needle aspiration was performed. Although
      acid-fast bacilli smears of the sputum and intrabullous fluid were negative,
      their cultures were found to be positive thereafter. M. kansasii was isolated and
      identified. After chemotherapy with antituberculous drugs, sub-fever improved and
      intrabullous fluid disappeared completely. Infected bulla caused by mycobacteria
      is very rare.

PMID- 15168465
TI  - [A case of desquamative interstitial pneumonia with bilateral hilar and
      mediastinal lymphadenopathy].
AB  - A 53-year-old man in whom reticulonodular shadows had been noted since 1999 in
      chest radiographs was admitted to our hospital in January 2003 with a complaint
      of persistent cough. His thoracic computed tomography (CT) showed diffuse ground
      glass opacities in both lung fields and bilateral hilar and mediastinal
      lymphadenopathy. Histopathological findings from video-assisted thoracoscopic
      surgical biopsy included diffuse, monotonous interstitial pneumonia with
      accumulation of macrophages in the alveolar spaces and many lymphoid follicles,
      which was compatible with desquamative interstitial pneumonia (DIP). There was
      follicular hyperplasia in the enlarged lymph node without a suggestion of
      granulomous disease. He responded well to corticosteroid administration,
      resulting in an improvement of his clinical condition associated with a decrease
      in the ground-glass opacities. The bilateral hilar and mediastinal
      lymphadenopathy was slightly reduced. Since we could find no literature reporting
      DIP with bilateral hilar and mediastinal lymphadenopathy on thoracic CT, we
      consider the diagnostic problems and therapeutic response of this case to warrant
      a brief report.

PMID- 15168466
TI  - [Pulmonary thromboembolism complicating right subclavian vein obstruction: case
      report].
AB  - We report a case of pulmonary thromboembolism, in which obstruction of the right
      subclavian vein, also called Paget-von Schroetter syndrome, was detected. The
      patient was a 39-year-old man (a scaffold constructor). He lost consciousness at
      work, and was admitted as an emergency case to our hospital. He had noticed
      gradually worsening dyspnea for 1 month. Chest radiography showed Westmark's sign
      in the lungs and enlarged hilar vascular markings on both sides. Pulmonary
      perfusion scintigraphy confirmed multiple flow defects. Upper and lower limb
      venography disclosed interruption of the right subclavian vein, leading to a
      diagnosis of pulmonary thromboembolism secondary to upper limb vein thrombosis.
      In patients who have pulmonary thromboembolism without an apparent underlying
      disease, the lifestyle and work habits should be considered and the possibility
      of subclavian vein thrombosis should be kept in mind.

PMID- 15168467
TI  - [A case of poorly differentiated lung adenocarcinoma showing air-space
      consolidation caused by aerogenic metastasis].
AB  - A 78-year-old woman was admitted to our hospital because of dyspnea. A chest
      radiograph and a computed tomogram on admission showed air-space consolidation in
      the left upper lung field, and so pneumonia was diagnosed. Although antibiotics
      were administered, the air-space consolidation did not improve. A transbronchial
      lung biopsy was performed, yielding a pathologic diagnosis of poorly
      differentiated lung adenocarcinoma. Despite combination chemotherapy with
      docetaxel and UFT, the air-space consolidation expanded, and the patient finally
      died of respiratory failure 3 months after diagnosis. Autopsy revealed air-space
      consolidation due to poorly differentiated lung adenocarcinoma, with large
      atypical cells diffusely floating in the alveolar spaces. It has been recognized
      that bronchiolo-alveolar carcinoma and well-differentiated lung adenocarcinoma
      present with air-space consolidation, reflecting the cancer cells lining the
      alveolar walls. However, in this case, the air-space consolidation was due to
      cancer cells diffusely floating in the alveolar spaces in aerogenic metastasis.
      It was considered that this is a rare case, which presented with a very
      interesting development pattern.

PMID- 15168468
TI  - [A case of paragonimiasis westermani with a worm migration track on chest CT].
AB  - A 59-year-old man with rusty-colored sputum was admitted for evaluation of a
      nodular shadow on his chest radiograph. Chest computed tomography (CT) revealed
      nodules and nodular opacities with a cavity in the right S3. Chest CT also showed
      clearly a double linear shadow other than the bronchovascular bundle, with a
      different course from that of the bronchovascular bundle, suggesting a worm
      migration track. The diagnosis of paragonimiasis westermani was confirmed by
      detection of Paragonimus eggs in a bronchoscopic aspirate smear and by
      immunoserological examination. The linear lesion on the chest CT is uncommon in
      paragonimiasis, but the finding is thought to be useful for the diagnosis of this
      disease.

PMID- 15168469
TI  - [Birth and maturation of proteins].

PMID- 15168470
TI  - [The functions of the ribosomal tunnel in a birth of proteins].

PMID- 15168471
TI  - [Reconstitution of in vitro protein maturation system: the pure approach for
      protein maturation].

PMID- 15168472
TI  - [Protein folding in vitro and in vivo].

PMID- 15168473
TI  - [Cellular functions of cytosolic Hsp70].

PMID- 15168474
TI  - [Mechanism of chaperonin function].

PMID- 15168476
TI  - [Functions of extracellular GroELs].

PMID- 15168475
TI  - [Role of GroEL in Escherichia coli cell division].

PMID- 15168477
TI  - [Single molecule imaging of chaperonin functions].

PMID- 15168478
TI  - [Application of chaperonin as a carrier for Q-dots].

PMID- 15168479
TI  - [Reaction mechanism of archaeal molecular chaperones].

PMID- 15168481
TI  - [Molecular chaperone Hsp90 and morphological evolution].

PMID- 15168480
TI  - [Involvement of Hsp90 in the quality control of signal transducing proteins].

PMID- 15168482
TI  - [Hsp47, an endoplasmic reticulum-resident molecular chaperone that plays the
      specialized role in procollagen biosynthesis].

PMID- 15168483
TI  - [Cytosolic chaperonin CCT: the most complex molecular chaperone?].

PMID- 15168484
TI  - [Protein traffic (in eukaryotic cells): mechanism of operation of the protein
      traffic control system in the cell].

PMID- 15168485
TI  - [Targeting and insertion of preproteins into the mitochondrial outer membrane].

PMID- 15168486
TI  - [Mitochondrial protein import and molecular chaperone].

PMID- 15168487
TI  - [Membrane topogenesis via type I signal-anchor sequence].

PMID- 15168488
TI  - [Nucleocytoplasmic protein transport and its multiplicity and complexity].

PMID- 15168489
TI  - [Nuclear pore complex and nucleocytoplasmic transport].

PMID- 15168490
TI  - [COPII-dependent vesicle formation and protein sorting from endoplasmic
      reticulum].

PMID- 15168491
TI  - [Retrograde transport].

PMID- 15168492
TI  - [p97-mediated membrane fusion is required for Golgi and ER assembly].

PMID- 15168493
TI  - [Seeds of the Golgi apparatus].

PMID- 15168494
TI  - [Protein targeting to thylakoids].

PMID- 15168495
TI  - [Protein import into chloroplasts: the role of GTP during the early stage of
      import].

PMID- 15168497
TI  - [Visualization of life of proteins].

PMID- 15168496
TI  - [Research on protein targeting innovates on present knowledge of plant
      peroxisomes].

PMID- 15168498
TI  - [Transport and motor protein].

PMID- 15168499
TI  - [Dynamin and endocytosis].

PMID- 15168500
TI  - [Protein trafficking and envelope biogenesis in bacteria].

PMID- 15168501
TI  - [Molecular architecture of protein translocase].

PMID- 15168502
TI  - [Function of YidC in the protein insertion into the cytoplasmic membrane of E.
      coli].

PMID- 15168503
TI  - [Localization of lipoproteins in Escherichia coli].

PMID- 15168505
TI  - [Passage of bacterial effectors into the host cell].

PMID- 15168504
TI  - [Transport of outer membrane proteins].

PMID- 15168506
TI  - [Type I secretion pathway: gram-negative bacterial ABC-exporter].

PMID- 15168507
TI  - [Quality control mechanism of proteins and cellular crisis management].

PMID- 15168509
TI  - [Roles of molecular chaperones and carbohydrate chains in the endoplasmic
      reticulum quality control].

PMID- 15168508
TI  - [ER quality control and ERAD: EDEM accelerates glycoprotein ERAD].

PMID- 15168510
TI  - [Unfolded protein response as a quality control mechanism of proteins].

PMID- 15168511
TI  - [How is ER stress sensed?].

PMID- 15168512
TI  - [Stress signaling from the endoplasmic reticulum].

PMID- 15168513
TI  - [Molecular mechanisms of ER stress-induced apoptosis].

PMID- 15168514
TI  - [Regulation of apoptosis by molecular chaperones].

PMID- 15168515
TI  - [Small heat shock proteins participate in the quality control of the protein in
      mammalian cells].

PMID- 15168516
TI  - [Dynamics of proteins in the endoplasmic reticulum].

PMID- 15168517
TI  - [Immunoregulatory role of the protein quality control system].

PMID- 15168518
TI  - [The role of lysosomal membrane glycoproteins].

PMID- 15168519
TI  - [Autophagy as a bulk protein degradation system: it plays various roles].

PMID- 15168520
TI  - [Ubiquitin and proteasome].

PMID- 15168521
TI  - [Ubiquitin ligases that recognize sugar chains].

PMID- 15168522
TI  - [Structural biology of ubiquitin and ubiquitin binding domain/motif].

PMID- 15168523
TI  - [AAA proteins as unfoldases].

PMID- 15168524
TI  - [Protein recycling systems in prokaryotic cells].

PMID- 15168525
TI  - [Quality control of cell surface proteins in E. coli].

PMID- 15168526
TI  - [Disaggregation of protein aggregates by ClpB chaperone].

PMID- 15168527
TI  - [Trans-translation: co-translation protein quality control system].

PMID- 15168528
TI  - [When trans-translation occurs?].

PMID- 15168529
TI  - [Recycling system of ribosomal proteins by Lon protease].

PMID- 15168531
TI  - [Proteome analysis of Bacillus subtilis].

PMID- 15168530
TI  - [Regulation of bacterial pathogenesis by proteases].

PMID- 15168532
TI  - [Proteases in Archaea].

PMID- 15168533
TI  - [Neurodegenerative disorders as protein misfolding diseases and organelle
      diseases].

PMID- 15168534
TI  - [Alzheimer's disease: focus on beta-amyloid and gamma-secretase].

PMID- 15168535
TI  - [Conformational stability of amyloid fibril: nanoscale needle].

PMID- 15168536
TI  - [Formation and dissociation of amyloid fibrils].

PMID- 15168537
TI  - [Amylospheroid and the 'morphometabolism' disease (conformational disease)].

PMID- 15168539
TI  - [BSE infection and prion replication].

PMID- 15168538
TI  - [Transmission of amyloidosis].

PMID- 15168540
TI  - [Mechanism of prion-fibril formation].

PMID- 15168541
TI  - [Intermediate conformer of prion and dynamics based drug design (DBDD)].

PMID- 15168542
TI  - [Dopaminergic neuronal death in Parkinson's disease: is accumulation of unfolded
      proteins a cause or effect?].

PMID- 15168543
TI  - [Therapeutic targets in polyglutamine diseases].

PMID- 15168544
TI  - [Mechanism of polyglutamine aggregate formation].

PMID- 15168545
TI  - [Neurodegenerative disease models of AAA proteins in C. elegans].

PMID- 15168546
TI  - [Motor neuron disease].

PMID- 15168547
TI  - [Cytotoxic effects of homopolyamino acids].

PMID- 15168549
TI  - [ER stress response and bipolar disorder].

PMID- 15168548
TI  - [Endoplasmic reticulum stress and diabetes].

PMID- 15168550
TI  - [Hereditary deficiencies of blood coagulation factors: from the viewpoints of
      intracellular transport and quality control].

PMID- 15168551
TI  - [Peroxisome biogenesis and human peroxisomal disorders].

PMID- 15168553
TI  - [Defects in mitochondrial protein import, folding and assembly, and mitochondrial
      disease].

PMID- 15168552
TI  - [Lysosomal storage disease].

PMID- 15168555
TI  - [Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar
      rats].
AB  - A 52-week study of oral-repeated-dose toxicity for the extraction powder of
      Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted
      in both genders of Wistar rats. The rats were administered a graded dose of GS at
      0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with the
      basal powder diet without GS, for 52 weeks. General conditions were recorded
      daily. Body weights and food consumptions were recorded weekly up to 12 weeks,
      and thereafter at longer intervals. At 26 weeks, for an intermediate examination,
      and 52 weeks, for the final examination, animals were subjected to hematology,
      serum chemistry, and pathological examination. None of the animals died in the
      period up to 52 weeks. No exposure-related changes in body-weight, in the food
      consumption, in the hematological examinations, or in the serum biochemical
      examinations were recognized. No histopathological alterations were seen. Thus,
      it was concluded that there was no toxic effect in rats treated with GS at up to
      1.00% in the diet for 52 weeks. The no-observable-effect level from this study is
      1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for female as mean daily
      intake, for 52 weeks.

PMID- 15168554
TI  - [Metabolic disturbance of tryptophan-nicotinamide conversion pathway by putative
      endocrine disruptors, bisphenol A and styrene monomer].
AB  - Bisphenol A, a monomer of polycarbonate plastics, disturbed the conversion
      pathway of the amino acid tryptophan to the vitamin nicotinamide. The conversion
      ratio of tryptophan to nicotinamide was reduced to 1/15 by feeding a diet
      containing 1% bisphenol A. A putative disturbing reaction is kynurenine-->3
      hydroxykynurenine, which is catalyzed by kynurenine monohydroxylase. This is an
      FAD-enzyme and requires NADPH as a coenzyme. Styrene monomer (1% addition to a
      normal diet) did not affect the food intake or the body weight, but slightly
      reduced the conversion ratio of tryptophan-nicotinamide.

PMID- 15168556
TI  - A histochemical method using a substrate of beta-glucuronidase for detection of
      genetically modified papaya.
AB  - A histochemical assay for detecting genetically modified (GM) papaya (derived
      from Line 55-1) is described. GM papaya, currently undergoing a safety assessment
      in Japan, was developed using a construct that included a beta-glucuronidase
      (GUS) reporter gene linked to a virus coat protein (CP) gene. Histochemical assay
      was used to visualize the blue GUS reaction product from transgenic seed embryos.
      Twelve embryos per fruit were extracted from the papaya seeds using a surgical
      knife. The embryos were incubated with the substrate 5-bromo-4-chloro-3-indolyl
      beta-D-glucuronide (X-Gluc) in a 96-well microtiter plate for 10-15 hours at 37
      degrees C. Seventy-five percent of GM papaya embryos should turn blue
      theoretically. The histochemical assay results were completely consistent with
      those from a qualitative polymerase chain reaction (PCR) method developed by this
      laboratory. Furthermore, the method was validated in a five-laboratory study. The
      method for detection of GM papaya is rapid and simple, and does not require use
      of specialized equipment.

PMID- 15168557
TI  - Detection of Leuconostoc strains at a meat processing plant using polymerase
      chain reaction.
AB  - To simplify the labor-intensive conventional routine testing of samples to detect
      Leuconostoc at a meat processing plant, we developed polymerase chain reaction
      (PCR) primers specific for Leuconostoc from 16S rRNA gene sequences. These
      primers did not detect other common lactic acid bacteria such as Lactobacillus
      plantarum, Lact. sake, Lact. fermentum, Lact. acidophilus and Weissella
      viridescens. PCR with this primer detected all Leuconostoc species tested (Leu.
      mesenteroides subsp. mesenteroides, Leu. pseudomesenteroides, Leu. carnosum, Leu.
      lactic, Leu. citreum, Leu. amelibiosum, Leu. gelidum), except for Leu. fallax,
      and no other lactic acid bacteria on agarose gel electrophoresis. The method
      could identify areas contaminated with Leuconostoc in a large-scale industrial
      meat processing plant. Of 69 samples analyzed, 34 were positive for Leuconostoc
      according to the conventional culture method (isolation of LAB producing dextran)
      and PCR, whereas 29 were negative according to both. Six samples were culture
      negative but positive by PCR. No false negative results were generated by PCR.
      The method is rapid and simple, is useful for routinely monitoring areas
      contaminated with Leuconostoc in meat processing plants, and could help to
      prevent the spoilage of meat products.

PMID- 15168559
TI  - Growth kinetics of Vibrio parahaemolyticus O3:K6 under varying conditions of pH,
      NaCl concentration and temperature.
AB  - The growth responses of Vibrio parahamolyticus to pH, NaCl concentration and
      temperature changes were studied using serotype O3:K6 and other strains. Growth
      curves were obtained for 27 different sets of conditions, comprised of three
      levels of NaCl concentration, pH and temperature. The temperature, pH and NaCl
      concentrations most favorable for growth were in the order of 25 degrees C, 20
      degrees C and 15 degrees C, pH 8, 7 and 5.8, and 1%, 3% and 7%, respectively. The
      bacteria grew most rapidly at 25 degrees C, at a pH of 7 or 8 in the presence of
      1% or 3% NaCl, with the population (initial, ca. 2.5 log CFU/mL) reaching a level
      log 7 CFU/mL at 12 h. A growth predictive model using the Gompertz equation was
      generated from the experimental data for any combination of NaCl concentration,
      pH and temperature within the range used in this study.

PMID- 15168558
TI  - [Effect of coexisting metals on determination of lead and cadmium in the plastic
      materials test of the Japanese Food Sanitation Law].
AB  - The effect of coexisting metals in a sample on the determination of lead and
      cadmium in plastics used for food contact materials was investigated. In the
      official method specified in the Japanese Food Sanitation Law, contents of lead
      and cadmium are determined by a dry incineration method using sulfuric acid. It
      was assumed that sometimes, coexisting metals in a sample may form insoluble
      sulfate and that lead sulfate might be adsorbed into the insoluble sulfate.
      Therefore, hydrochloric acid was added to the ash, to turn formed insoluble
      sulfate into soluble compounds (HCl addition method). We found that recoveries of
      cadmium were not affected in the presence of other metals except when calcium
      exceeded 20 mg/g in both methods. Recoveries of lead decreased in the presence of
      barium exceeding 0.1 mg/g or calcium exceeding 10 mg/g in the official method.
      However, improvement of recoveries was achieved with the HCl addition method and
      by reducing the sample amount to one-tenth (0.1 g) of that specified in the
      official method.

PMID- 15168560
TI  - [Simultaneous analysis of glyphosate and glufosinate in vegetables and fruits by
      GC-FPD].
AB  - A rapid analytical method for residues of the herbicide, glyphosate [N
      (phosphonomethyl)glycine], glufosinate [DL-homoalanine-4-yl(methyl)phosphinic
      acid] and glufosinate metabolite (MPPA: 3-methylphosphinicopropionic acid) in
      vegetables and fruits was developed by improving the bulletin method of
      glufosinate. 50 mL of solution extracted with water (corresponding to 2 g of the
      sample) was loaded on a column packed with 5 mL of anion exchange resin and then
      the trapped glyphosate, glufosinate and MPPA were eluted with 60 mL of 50% acetic
      acid. After derivatization with trimethyl orthoacetate, the derivatives were
      purified and separated on a Florisil cartridge column. The determination of the
      derivatives was performed with GC-FPD. The detection limits for glyphosate,
      glufosinate and MPPA were 0.01 microgram/g, 0.01 microgram/g and 0.005
      microgram/g, respectively. The recoveries from fortified samples were 83.5-89.8%
      for glyphosate, 77.9-92.2% for glufosinate and 75.0-87.2% for MPPA.

PMID- 15168561
TI  - [Production of acrylamide in agricultural products by cooking].
AB  - Some model studies were performed using various agricultural Products, to clarify
      the relation between cooking conditions and production of acrylamide (AA). Disc
      chips made from dried mashed potato, corn meal, wheat flour, rice flour (jyohshin
      ko) and glutinous rice flour (shiratama-ko), and dried sesame (arai-goma) and
      dried almond were baked at 120-200 degrees C for 5-20 min, and the samples were
      analyzed for the levels of AA. When the samples were baked for 10 min, the
      highest production of AA was observed at 180-200 degrees C. When the samples were
      baked at 180 degrees C, AA levels in agricultural products except sesame were
      highest after baking for 10 min. Vegetables and fruit were baked at 220 degrees C
      for 5 min with a oven, high AA concentrations were found in baked potato,
      asparagus, pumpkin, eggplant and green gram sprouts. Concentrations of AA in
      potato, asparagus and green gram sprouts baked after being pre-cooked by
      microwave irradiation were higher than those in the products baked without being
      precooked. On the other hand, the precooking by boiling reduced the production of
      AA by baking to 1/10-1/4. Acrylamide was not found in microwaved or boiled
      vegetables. High free asparagine concentrations in crops tended to result in high
      concentrations of AA being produced by heating the agricultural products.

PMID- 15168563
TI  - [Simultaneous determination of organophosphorus pesticides in cruciferous
      vegetables by dual-column GC with pulsed FPD and FTD].
AB  - We evaluated simultaneous analytical methods for organophosphorus pesticides in
      cruciferous vegetables by gas chromatography (GC). Firstly, 36 pesticides were
      selected on the basis of monitoring data (April 1996-March 2003) in Aichi
      Prefecture. A sample was extracted with acetonitrile and the acetonitrile layer
      was separated by salting-out. The extract was cleaned up with gel permeation
      chromatography (GPC), and then with a tandem silica-gel/PSA mini-column. The test
      solution was subjected to dual-column GC equipped with a pulsed FPD (P mode, Rtx
      OPPesticides column) and a FTD (Rtx-OPPesticides 2 column). Organophosphorus
      pesticides in such sulfur-rich matrices as cabbage and radish were determined
      without any serious interfering peaks on the pulsed FPD chromatograms after
      diluting the extracts 10- to 20-fold (0.25-0.5 mg/L of sample). The method was
      applied to cruciferous vegetables to demonstrate its usefulness in routine
      analysis.

PMID- 15168562
TI  - [Survey on the concentrations of hormones (estradiol-17 beta, progesterone,
      testosterone) in bovine muscles].
AB  - Natural sex hormones, estradiol-17 beta (EST), progesterone (PRO) and
      testosterone (TES), in sixty domestic bovine muscles and forty bovine muscles
      imported from USA and Australia were determined by radioimmunoassay. The EST, PRO
      and TES levels (mean +/- standard deviation) in domestic samples (n = 60) was
      1.15 +/- 1.87 ppt, 3.19 +/- 5.80 ppb and 30.9 +/- 122.1 ppt on a whole basis,
      respectively. The hormone levels in muscles was presumed to reflect sex, estrous
      cycle, and so on. The hormone levels in imported bovine muscles (n = 40) were
      3.33 +/- 2.83 ppt (EST), 0.52 +/- 0.50 ppb (PRO) and 8.8 +/- 13.0 ppt (TES),
      respectively.

PMID- 15168564
TI  - [Heterotrophic bacteria in tap water].

PMID- 15168565
TI  - Review panel on Haemophilus influenzae type b (Hib) disease burden in Bangladesh,
      Indonesia and other Asian countries, Bangkok, 28-29 January 2004.

PMID- 15168567
TI  - Perspectives. Washington on health care: it's the drug prices, stupid.

PMID- 15168566
TI  - Food safety in developing countries--building capacity.

PMID- 15168568
TI  - Top compliance issues for all of 2003.

PMID- 15168569
TI  - When the old care for the older: one elderly caregiver's story.

PMID- 15168570
TI  - Occupational therapy and home health. A perfect fit.

PMID- 15168571
TI  - A world apart. The challenges and rewards of rural hospice.

PMID- 15168573
TI  - Never give up. A stroke survivor's road to recovery.

PMID- 15168572
TI  - Ross' story. One man's triumphant journey through life and death.

PMID- 15168574
TI  - The best birthday present.

PMID- 15168575
TI  - Home care aides reaping personal rewards.

PMID- 15168576
TI  - Photo postcard campaign puts human faces on home care & hospice.

PMID- 15168577
TI  - Older nurses embrace hospice & home care.
AB  - Older nurses who have "done their time" in hospital wards sometimes find home
      health or hospice nursing a welcome and rewarding change of pace. While their
      maturity often gives them the empathy and compassion that can bring comfort to
      their patients, their extensive experience supplies them with the knowledge they
      need to work confidently in an independent setting.

PMID- 15168578
TI  - Picture this: photo frame prolongs independent living.

PMID- 15168579
TI  - "Help me, I'm cold.".

PMID- 15168580
TI  - MedPAC's upcoming report to Congress on the Medicare hospice benefit:
      recommendations for a changing world.

PMID- 15168581
TI  - Shedding light on age-related vision loss.

PMID- 15168582
TI  - Tell a positive 'capitation story' in marketing your practice.

PMID- 15168583
TI  - Employer coalition proposes to reduce costs, improve quality.
AB  - Taking on a challenge from a large local employer coalition, capitated groups re
      gearing up to bid on contracts under managed competition in Indianapolis.

PMID- 15168585
TI  - HealthCare partners overhauls its injectable drug management program.
AB  - With pharmacy costs rising nationally 8% to 15% annually and the cost of
      injectables rising at an even higher 15% to 25% clip, HealthCare Partners is
      looking for ways to improve its injectables authorization process, develop a more
      effective evaluation method for its therapeutic guidelines, and better integrate
      its utilization management information system with billing.

PMID- 15168584
TI  - Health care cost increases begin to slow, but reasons are debatable.

PMID- 15168587
TI  - Chronic graft-versus-host disease: clinical features and grading systems.
AB  - Chronic graft-versus-host disease (GVHD) is the prime cause of transplantation
      related mortality late after marrow grafting and contributes directly or
      indirectly to most nonmalignant complications. The main clinical symptoms and
      diagnostic problems of chronic GVHD are summarized here. A major issue in
      treating chronic GVHD is to assess disease severity. A critical review of
      published grading systems failed to demonstrate that any system is better than
      the others. Prospective validation of the Johns Hopkins grading scale is timely
      and warranted.

PMID- 15168586
TI  - The pathophysiology of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) still remains the most significant
      complication after allogeneic hematopoietic stem cell transplantation. The
      disease usually appears after day 100 and is characterized by signs and symptoms
      similar to autoimmune diseases. The pathophysiology of chronic GVHD is poorly
      understood because of the lack of highly satisfactory animal models and basic
      studies in patients. It has not been clearly determined whether the disease is a
      distinct entity or a continuation of acute GVHD. In experimental and clinical
      studies of chronic GVHD, thymic atrophy, lymphocyte depletion, and autoantibody
      formation have been described. Conditioning regimens and acute GVHD may disrupt
      thymic function and dysregulate the negative selection process of potentially
      autoreactive T-lymphocytes. Disruption of thymic apoptosis and failure to
      eliminate the majority of self-reactive lymphocytes may lead to impairment of
      lymphocyte homeostasis and self tolerance. Expansion and effector functions of
      autoreactive T-cells will then promote autoreactive B-cell activation and
      production of autoantibodies with target-organ damage. Chronic GVHD requires
      continuous CD4+ T-cell help for B-cells and is known as T-helper 2 (Th2) disease.
      Murine models have demonstrated the roles of interleukin (IL)-12 and IL-18 in
      chronic GVHD. IL-12 may cause an increase in donor CD8+ cytotoxic T-cells leading
      to conversion of chronic GVHD to an acute form. In contrast, IL-18 prevents
      chronic GVHD by decreasing numbers of CD4+ (Th2) cells and host-reactive B-cell
      activation and reducing alloantigen-specific immune response. Mouse and human
      cellular genomics coupled with advances in cell biology in donor-recipient
      tolerance will improve our understanding of transplantation immunology and may
      offer new approaches to the challenge of ameliorating chronic GVHD.

PMID- 15168588
TI  - Diagnosis and clinical management of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) occurs in approximately 60% of patients
      who survive for more than 100 days after receiving an allogeneic marrow or
      peripheral blood stem cell transplant without T-cell depletion of the graft.
      Chronic GVHD represents a major cause of morbidity and mortality among
      hematopoietic stem cell transplant recipients. Risk factors for the development
      of chronic GVHD and for mortality among patients who develop this complication
      have been defined, but the pathogenesis of chronic GVHD is not well understood.
      This review discusses the clinical manifestations that lead to a diagnosis of
      chronic GVHD and outlines an approach for therapy with glucocorticoids and
      extended administration of a calcineurin inhibitor. The judicious use of
      glucocorticoids at the lowest effective dose and alternate-day administration can
      minimize steroid-related side effects. Antibiotic prophylaxis to prevent
      infection and supportive care to minimize morbidity and prevent disability are
      critically important components in the management of patients with chronic GVHD.
      Approximately 50% of patients with chronic GVHD are able to discontinue
      immunosuppressive treatment within 5 years after the diagnosis, and 10% require
      continued treatment beyond 5 years. The remaining 40% die or develop recurrent
      malignancy before the chronic GVHD resolves. An improved understanding of the
      pathogenesis of the disease is needed to develop more effective therapy.

PMID- 15168589
TI  - Second malignant neoplasms following hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation is being successfully used to treat a
      variety of malignant and nonmalignant disorders. This therapy has resulted in an
      increasing number of survivors who are at risk for adverse long-term outcomes,
      including the development of second and subsequent malignant neoplasms. We review
      the incidence and spectrum of posttransplantation malignancies and discuss risk
      factors and future directions for research.

PMID- 15168590
TI  - E148Q/M694I mutation in 3 Japanese patients with familial Mediterranean fever.
AB  - We describe 3 unrelated Japanese patients with familial Mediterranean fever (FMF)
      due to a compound heterozygous E148Q/M694I mutation in the MEFV gene. The first
      patient is a 38-year-old man who also has chronic myelogenous leukemia (CML).
      Because genomic DNA analysis of the patient's nail revealed the E148Q/M694I
      mutation, we concluded that the individual mutations were obtained congenitally.
      Interferon alpha therapy was effective against not only the CML but also the FMF.
      The second patient is a 42-year-old man with consanguineous parents and a 14-year
      history of recurrent lower abdominal and back pain associated with fever. He
      successfully responded to colchicine treatment. The third patient is a 23-year
      old woman who has a family history of FMF and since the age of 11 years has had
      recurrent chest and abdominal pain with fever. The onset of FMF was at an early
      age in this case, in contrast with the late onset of the disease in the first 2
      cases. This patient's mother also has a heterozygous M694I mutation and
      experienced the same symptoms until 30 years of age. Our data suggest that it
      should be recognized that there are more FMF patients in Japan than previously
      expected and that the frequency of the E148Q/M694I mutation may be significant in
      Japanese FMF patients.

PMID- 15168591
TI  - Alterations of common chromosome fragile sites in hematopoietic malignancies.
AB  - Conditions of replication stress affect expression of all common fragile regions,
      including FRA3B (chromosome 3p14.2), FRA16D (16q23), FRA6E (6q26), FRA7G
      (7q31.2), and FRAXB (Xp22.3), and a number of cancer cell lines exhibit
      homozygous deletions in 2 or more common fragile regions. In 1996 the fragile
      histidine triad (FHIT) gene was isolated from the region encompassing the most
      active fragile FRA3B locus, and recently the WW domain-containing oxidoreductase
      gene (WWOX) was identified at FRA16D. These 2 fragile genes are altered or
      deleted in various epithelial tumors and exhibit tumor suppressor function.
      Aberration or absence of WWOX expression recently was detected in primary
      hematopoietic malignancies. The aberration resulted not only from genomic
      deletions but also possibly from epigenetic modifications associated with
      expression of fragility. Thus chromosomal aberrations at common fragile sites, in
      addition to the well-defined hallmark leukemia chromosome translocations, are
      involved in clinicopathological outcomes of hematopoietic malignancies.

PMID- 15168592
TI  - Clinical significance of minimal residual disease in childhood acute myeloid
      leukemia.
AB  - Many studies have assessed the clinical significance of the detection of minimal
      residual disease (MRD) in acute leukemia. Thus far, many studies have suggested
      that MRD detection to evaluate the response to chemotherapy is useful for
      predicting the prognosis of childhood acute lymphoblastic leukemia (ALL).
      However, few studies have reported on the significance of MRD in childhood acute
      myeloid leukemia (AML), because of small numbers of patients and limited
      availability of MRD markers. Therefore, we monitored MRD using currently
      available markers at several points during the treatment for childhood AML and
      tried to intensify the treatment based on the results of MRD. Thirty-one patients
      (26 de novo cases and 5 other cases) were examined for MRD between February 1999
      and May 2002. After the first consolidation therapy (consolidation 1), the
      expression of Wilms tumor gene (WT1) and/or leukemia-specific fusion genes such
      as AML1/MTG8, PML/RAR alpha, and MYH11/CBF beta were analyzed. Patients with
      positive MRD but in hematological remission at that point were recommended to
      undergo stem cell transplantation (SCT). Positive WT1 expression (more than 10(3)
      copies/microgram RNA) was detected in 18 of 31 patients (58.1%) at onset. After
      consolidation 1 therapy, the WT1 expression became negative in 14 of 18 patients.
      The AML1/MTG8 fusion gene was expressed in 8 patients, PML/RAR alpha was
      expressed in 3 patients, and MYH11/CBF beta was expressed in 1 patient. Four of
      the 8 patients with AML1/MTG8 expression and all 3 with PML/RAR alpha expression
      also demonstrated positive WT1 expression at onset. Eight (5 de novo cases and 3
      other cases) of the 31 patients had no available MRD markers. Four patients who
      showed pesistently high expression of WT1 after consolidation 1 therapy underwent
      SCT, and only 1 patient remained in complete remission (CR). Among 14 patients
      who became negative for WT1 expression, 6 patients received SCT for various
      reasons. Among 8 patients with the AML1/MTG8 fusion gene, 2 became MRD negative
      and 6 continued to be positive. Four of these 6 patients underwent SCT, and all
      but one who underwent syngeneic SCT became MRD negative. On the other hand, 1 of
      the 2 patients who continued on chemotherapy continued to be MRD positive,
      suggesting a graft-versus-leukemia effect in allogeneic SCT. All patients with
      the PML/RAR alpha and MYH11/CBF beta fusion gene continued to be in CR. The 3
      year event-free survival in de novo AML was 69.4% +/- 9.8% (n = 26), a result
      that is encouraging and superior to other reported outcomes. Thus, an MRD-based
      treatment strategy together with conventional risk factors appears to be required
      for further improving the outcomes of AML.

PMID- 15168593
TI  - Granulocytic sarcoma presenting with malignant anasarca in a patient with
      secondary acute myeloid leukemia.
AB  - Granulocytic sarcomas (GS) are rare extramedullary tumor masses composed of
      immature cells derived from the hematopoietic myeloid series. GS occur in 3% to
      7% of cases of acute myeloid leukemia (AML) and can present before, during, or
      even after the diagnosis of AML. GS can involve different organs, individually or
      simultaneously, including the skin, lymph nodes, bone, breast, central nervous
      system, and lung among others. GS involving peritoneal and pleural fluids is a
      rare presentation. We present an unusual case of a patient with myelodysplastic
      syndrome whose disease progressed into a secondary AML and developed GS in the
      ascitic and pleural effusions as the predominant manifestation of disease
      progression.

PMID- 15168594
TI  - Markers of endothelial and in vivo platelet activation in patients with essential
      thrombocythemia and polycythemia vera.
AB  - We investigated endothelial and in vivo platelet activation in a cohort of 52
      patients with essential thrombocythemia (ET) and polycythemia vera (PV) before
      and after cytoreductive treatment, 22 healthy controls, and 17 patients with
      acute cerebrovascular ischemia (ACVI) and normal platelet counts. We measured
      platelet expression of CD62P and CD63 antigens and levels of soluble vascular
      cell adhesion molecule 1 (sVCAM-1). We found increased in vivo platelet
      activation in all patients with ET and PV, both before and after cytoreductive
      treatment, compared with controls. In patients with arterial thrombosis, platelet
      expression of CD62P, and in patients with erythromelalgia, expression of both
      markers was higher compared with expression in patients without thrombotic
      complications. In patients with ET and PV before and after treatment, sVCAM-1
      expression was increased compared with expression in controls but also compared
      with expression in patients with ACVI and normal platelet counts. In patients
      with arterial thrombosis and erythromelalgia, in vivo platelet activation
      correlated with the level of sVCAM-1. Our findings indicated that in vivo
      platelet activation reflects intrinsic platelet defects in patients with ET and
      PV, persists after cytoreductive treatment, and results in endothelial damage,
      probably through release of angiogenic factors and/or activation of white blood
      cells.

PMID- 15168596
TI  - Phase I study of the combination of irinotecan hydrochloride, carboplatin, and
      dexamethasone for the treatment of relapsed or refractory malignant lymphoma.
AB  - A phase I study of irinotecan hydrochloride (CPT-11), carboplatin, and
      dexamethasone treatment in 7 patients with relapsed lymphoma and 7 patients with
      refractory lymphoma was conducted to evaluate the maximal tolerated dose. The 6
      female and 8 male patients had a median age of 63 years (range, 45-73 years), a
      median performance status of 0 (range, 0-2), and a median disease stage of IV.
      This study included patients with diffuse large B-cell lymphoma (n = 5), adult T
      cell leukemia/lymphoma (n = 2), mantle cell lymphoma (n = 2), follicular lymphoma
      (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), anaplastic large cell
      lymphoma (n = 1), and Hodgkin's lymphoma (n = 1). All patients had received
      anthracycline-containing combination chemotherapy prior to this therapy. The
      starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage
      escalation increments of 5 mg/m2 per day were planned, with fixed dosages of
      carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3
      and days 8-10). Five patients were enrolled at level 1, 3 at level 2, 4 at level
      3, and 2 at level 4. Ten patients (71%) and 11 patients (79%) experienced grade 3
      or 4 hematologic toxicities of leukocytopenia and neutropenia, respectively.
      Three patients (29%) and 9 patients (64%) experienced grade 3 or 4
      thrombocytopenia and anemia, respectively. Two patients who received 30 mg/m2
      (level 4) of CPT-11 developed sepsis. We concluded that the recommended dose of
      CPT-11 with carboplatin and dexamethasone is 25 mg/m2. No deaths were related to
      this chemotherapy, and no patient developed liver dysfunction. The overall
      response rate was 36%. We conclude that the combination therapy of CPT-11,
      carboplatin, and dexamthasone is effective as salvage therapy but that the
      duration of response is too short.

PMID- 15168595
TI  - Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell
      lymphoma and an anaplastic variant of a diffuse large B-cell type of non
      Hodgkin's lymphoma and strongly expressing p53 protein.
AB  - We report a case of composite lymphoma consisting of peripheral T-cell lymphoma
      and an anaplastic variant of diffuse large B-cell lymphoma (DLBCL) and associated
      with Epstein-Barr virus (EBV) infection and strong p53 expression. A 65-year-old
      Japanese woman developed fever and generalized lymphadenopathy. A biopsy of the
      cervical node revealed the morphology of malignant lymphoma with 2 kinds of
      lymphoma coexisting in 1 lymph node. One lymphoma type consisted of immunoblastic
      large cells with the T-cell marker phenotype CD3+, CD45RO/UCHL-1+, CD20/L26-,
      CD79-, CD10-, CD30-, and CD15-; the other type consisted of large cells with
      abundant cytoplasm and pleomorphic nuclei with the marker phenotype CD79+,
      CD20/L26+, CD45RO/UCHL-1-, CD3-, CD10-, CD30+, NPM/ALK-, and CD15-. Therefore,
      the diagnosis was composite lymphoma of peripheral T-cell lymphoma and an
      anaplastic variant of DLBCL, stage IVB, because the patient had bone marrow
      involvement with peripheral T-cell lymphoma. The biopsy led to findings of latent
      type II EBV-associated lymphoma in both the peripheral T-cell lymphoma and the
      anaplastic variant of DLBCL as the result of positive signals for EBV small RNAs
      by in situ hybridization, positive immunostaining results for EBV latent membrane
      protein 1 antibody, and negative immunostaining results for EBV nuclear antigen
      2. Immunostaining of the mass with p53 antibody also yielded positive results for
      both types of lymphoma cells. This case suggests that the immunocompromised state
      of this patient with EBV-related peripheral T-cell lymphoma allowed the emergence
      of an EBV-related anaplastic variant of DLBCL and suggests a close relationship
      between p53 expression and latent EBV infection.

PMID- 15168597
TI  - Durable remission by sobuzoxane in an HIV-seronegative patient with human
      herpesvirus 8-negative primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is recognized as a unique clinicopathological
      entity associated with human herpesvirus 8 (HHV-8), and it occurs almost
      exclusively in human immunodeficiency virus (HIV)-infected individuals. In the
      majority of PEL cases, Epstein-Barr virus (EBV) has been found in the tumor cells
      as well. We describe here an elderly HIV seronegative female patient with PEL in
      the pleura and pericardium not associated with HHV-8 or EBV. Cytologic
      examinations of the pleural effusion revealed large lymphoma cells with
      immunophenotypes positive for CD8, CD10, CD19, CD20, CD22, CD24, CD45, and HLA-DR
      but negative for CD30 and surface immunoglobulin. Chromosome analysis showed
      complicated abnormalities including add(3)(q27). Immunoglobulin gene
      rearrangement was detected by Southern blotting; however, c-myc, Bcl-2, and Bcl-6
      genes were not rearranged. The patient was treated with a modified CHOP
      (cyclophosphamide, hydroxydoxorubicin, oncovine, and prednisolone) regimen, and
      achieved remission. Recurrence of PEL in the pericardium as effusion lymphoma was
      found 3 months after the discontinuation of CHOP. After approximately 1 year of
      intermittent multiagent salvage therapy for pericardial recurrences, a treatment
      that resulted in a partial response, 3 cycles of monotherapy with sobuzoxane were
      administered. At the time of this report the patient had been free from PEL for
      more than 18 months without chemotherapy.

PMID- 15168598
TI  - Monitoring the expression profiles of doxorubicin-resistant K562 human leukemia
      cells by serial analysis of gene expression.
AB  - We examined the expression profiles of doxorubicin-resistant K562 cells by serial
      analysis of gene expression (SAGE) to identify novel and/or partially
      characterized genes that might be related to drug resistance in human leukemia.
      SAGE complementary DNA (cDNA) libraries were constructed from K562 and
      doxorubicin-resistant K562 (K562/ADM) cells, and concatamer sequences were
      analyzed with SAGE 2000 software. We used 9792 tags in the identification of 1076
      different transcripts, 296 of which were similarly expressed in K562 and K562/ADM
      cells. There were 343 genes more actively expressed in K562/ADM than in parental
      K562 cells and 437 genes expressed less often in K562/ADM cells. K562/ADM cells
      showed increased expression of well-known genes, including the genes for spectrin
      beta, eukaryotic translation initiation factor 1A (EIF1A), RAD23 homolog B,
      laminin receptor 1, and polyA-, RAN-, and PAI-1 messenger RNA-binding proteins.
      K562/ADM cells showed decreased expression of the genes for fatty acid desaturase
      1 (FADS1), hemoglobin epsilon 1, N-myristoyltransferase 1, hemoglobin alpha 2,
      NADH dehydrogenase Fe-S protein 6, heat shock 90-kDa protein, and karyopherin
      beta 1. Quantitative reverse transcription-polymerase chain reaction analysis
      confirmed the increased expression of EIF1A and the decreased expression of FADS1
      in K562/ADM cells. Prior to this investigation, such differences in the
      expression of these genes in doxorubicin-resistant leukemia cells were unknown.
      Although we do not provide any evidence in the present report for the potential
      roles of these genes in drug resistance, SAGE may provide a perspective into our
      understanding of drug resistance in human leukemia that is different from that
      provided by cDNA microarray analysis.

PMID- 15168599
TI  - Thalidomide-induced severe neutropenia during treatment of multiple myeloma.
AB  - Recent reports have shown that thalidomide has antiangiogenic activity and is
      effective for the treatment of refractory multiple myeloma. Unlike other
      antineoplastic drugs, thalidomide is reported to rarely cause severe hematologic
      toxicity. In Keio University Hospital, 44 patients with refractory multiple
      myeloma, including 18 who had relapsed after hematopoietic stem cell
      transplantation, were treated with this drug as a single agent. Severe grade 3 or
      4 neutropenia during thalidomide treatment was observed in 10 patients. This
      phenomenon was not noted in previous reports. Neutropenia usually occurred in the
      first or second week of treatment. Concomitant progression of thrombocytopenia
      occurred in 5 cases, and bone marrow hypoplasia without a significant increase in
      myeloma cell numbers was also observed in 5 cases. Neutropenia was not correlated
      with anti-tumor response or the plasma concentration of thalidomide but was more
      frequently observed in patients with a low neutrophil and platelet count, anemia,
      or a high plasma cell percentage in the bone marrow before thalidomide treatment.
      Thus, this drug should be used carefully for patients with pretreatment cytopenia
      or a high tumor burden in the bone marrow.

PMID- 15168600
TI  - Successful treatment of chronic disseminated candidiasis with caspofungin and
      itraconazole in a patient with progressive acute leukemia and prolonged
      neutropenia.
AB  - Severe fungal infections remain a significant cause of morbidity and mortality in
      neutropenic patients undergoing dose-intensive chemotherapy for malignant
      diseases. Chronic disseminated candidiasis (CDC) is a life-threatening
      complication in neutropenic patients because of the lack of responsive
      hematopoietic precursor cells. Resolution of Candida organ lesions after
      hematopoietic reconstitution may take months. Here, we report the case of a 19
      year-old neutropenic woman with relapsed acute myelogenous leukemia and
      candidiasis of liver, spleen, and kidneys. Antifungal treatment was initiated
      using fluconazole and caspofungin but was changed to itraconazole and
      caspofungin. Despite elevated C-reactive protein (CRP) levels and detectable
      Candida organ lesions, antileukemic therapy was restarted with interleukin 2 at
      the same time as antimicrobial treatment. Eight weeks after the start of
      interleukin therapy, CRP levels and organ lesions were decreased significantly
      irrespective of continuing neutropenia. This case report describes the successful
      treatment of CDC during neutropenia using combination antifungal therapy and
      suggests controlled studies to establish optimal therapeutic strategies.

PMID- 15168601
TI  - Fludarabine- and cyclophosphamide-based nonmyeloablative conditioning regimen for
      transplantation of chronic granulomatous disease: possible correlation with
      prolonged pure red cell aplasia.
AB  - An 18-year-old patient with chronic granulomatous disease who had had at least 2
      episodes of life-threatening Aspergillus pneumonia was treated with
      nonmyeloablative allogeneic stem cell transplantation (NSCT) from an HLA
      identical and major ABO-incompatible sibling. The conditioning regimen consisted
      of cyclophosphamide at a dose of 60 mg/kg (days -5, -4) and fludarabine at a dose
      of 30 mg/m2 (days -5, -4, -3, -2, -1). Full donor T-cell engraftment was attained
      on day 28, and full myeloid engraftment was established by day 150 after
      tacrolimus withdrawal. The bacteriocidal activity of neutrophils, as indicated by
      flow cytometry with the use of a dichlorofluorescein diacetate oxidation assay,
      remained low until 150 days after transplantation, but no infection was detected,
      a finding that suggests mixed chimerism of granulocytes controlled infection.
      Graft-versus-host disease and severe regimen-related toxicity (grade 3 or
      greater) were not observed. This patient developed prolonged pure red cell
      aplasia, possibly caused by persistent antidonor isohemagglutinin produced by the
      residual host B-cells. The aplasia resolved with the combination of
      erythropoietin, double filtration plasmapheresis, and rituximab. In the setting
      of major ABO-incompatible NSCT, a fludarabine- and cyclophosphamide-based
      conditioning regimen may lead to prolonged PRCA.

PMID- 15168602
TI  - Spontaneous pneumothorax developed in patients with bronchiolitis obliterans
      after unrelated hematopoietic stem cell transplantation: case report and review
      of the literature.
AB  - Spontaneous pneumothorax following unrelated hematopoietic stem cell
      transplantation developed in our 2 patients with bronchiolitis obliterans.
      Bronchiolitis obliterans is a form of obstructive airway disease and is
      considered a manifestation of chronic graft-versus-host disease (GVHD). Both of
      the patients were the recipients of marrow from HLA-matched unrelated donors
      after a preparative regimen with total body irradiation. Chronic GVHD after
      transplantation is a common feature in these cases. In contrast to other patients
      with pneumothorax described in the literature, our patients did not develop
      bullae. We describe a pneumothorax secondary to bronchiolitis obliterans that
      complicated the posttransplantation course.

PMID- 15168603
TI  - Inversions of the factor VIII gene in Japanese patients with severe hemophilia A.
AB  - Hemophilia A is genetically very heterogeneous because disease-causing mutations
      involving deletions, point mutations, insertions, and inversions are scattered
      throughout the factor VIII gene. Of these mutations, inversions, which are
      intrachromosomal recombinations between int22h-1 (intron 22 homologous region 1)
      and 1 of 2 other extragenic copies located 500 kilobases upstream, are the more
      frequently found defects, especially in patients with severe hemophilia A.
      Reportedly, approximately half of all severe hemophilia A patients have
      inversions in intron 22. A group of unrelated patients from the middle of Japan
      with severe hemophilia A were screened by Southern blot analysis for gene
      inversions. Forty-two of 100 severely affected patients presented factor VIII
      gene rearrangements. Of these patients, 36 exhibited the distal type of
      inversion, and 6 exhibited the proximal type. No other variant type of
      recombination was observed. In this study, neither the prevalence of inhibitor
      development against factor VIII nor the frequency of sporadic cases in the group
      presenting gene inversions was significantly different from that in the group
      without chromosomal inversions. Southern blot analysis successfully detected a
      carrier in a hemophilia family for which no patient was available. Genetic
      counseling of patients with severe hemophilia A and their families will be
      considerably improved, because the inversions occur in 42% of the Japanese
      patients with severe hemophilia.

PMID- 15168604
TI  - Introduction. Extremophilic archaea and bacteria.

PMID- 15168606
TI  - Transport of compatible solutes in extremophiles.
AB  - Salt-tolerant as well as moderately halophilic and halophilic organisms have to
      maintain their turgor. One strategy is to accumulate small organic compounds,
      compatible solutes, by de novo synthesis or uptake. From a bioenergetic point of
      view, uptake is preferred over biosynthesis. The transport systems catalyzing
      uptake of compatible solutes are of primary or secondary nature and coupled to
      ATP hydrolysis or ion (H+, Na+) symport. Expression of the transporter genes as
      well as the activity of the transporters is regulated by salinity/osmolarity and
      one of the key questions is how salinity or osmolarity is sensed and the signal
      transmitted as far as to gene expression and transporter activation. Recent
      studies shed light on the nature and the activation mechanisms of solute
      transporters in extremophiles, and this review summarizes current knowledge on
      the structure, function and osmo- or salt-regulation of transporters for
      compatible solutes in extremophiles.

PMID- 15168605
TI  - Insights into ABC transport in archaea.
AB  - In archaea, ATP-binding cassette (ABC) transporters play a crucial role in
      substrate uptake, export, and osmoregulation. Archael substrate-binding-protein
      dependent ABC transporters are equipped with a very high affinity for their
      cognate substrates which provide these organisms with the ability to efficiently
      scavenge substrates from their environment even when present only at low
      concentration. Further adaptations to the archaeal way of life are especially
      found in the domain organization and anchoring of the substrate-binding proteins
      to the membrane. Examination of the signal peptides of binding proteins of 14
      archael genomes showed clear differences between euryarchaeotes and
      crenarchaeotes. Furthermore, a profiling and comparison of ABC transporters in
      the three sequenced pyrococcal strains was performed.

PMID- 15168607
TI  - DNA transport and natural transformation in mesophilic and thermophilic bacteria.
AB  - Comparative genome analyses revealed a massive DNA exchange between microbes of
      distant evolutionary lineages. This phenomenon known as horizontal, or lateral,
      gene transfer has a tremendous impact in the evolution of prokaryotes. Here, the
      process of DNA transport via genetic transformation is discussed. This review
      will focus on the process of DNA uptake mediated by type IV pilin-like proteins
      in Gram-positive and Gram-negative bacteria. Three tentative models of
      transformation machineries comprising components similar to proteins of type IV
      pili and type II secretion are presented. A comparative discussion of the
      structure of DNA translocators and the underlying mechanism of transfer of free
      DNA in mesophilic and extremely thermophilic bacteria highlights conserved and
      distinctive features of the DNA translocators in mesophilic and thermophilic
      bacteria.

PMID- 15168608
TI  - Extreme secretion: protein translocation across the archael plasma membrane.
AB  - In all three domains of life, extracytoplasmic proteins must overcome the hurdle
      presented by hydrophobic, lipid-based membranes. While numerous aspects of the
      protein translocation process have been well studied in bacteria and eukarya,
      little is known about how proteins cross the membranes of archaea. Analysis to
      date suggests that archael protein translocation is a mosaic of bacterial,
      eukaryal, and archaeal features, as indeed is much of archaeal biology. Archaea
      encode homologues of selected elements of the bacterial and eukaryal
      translocation machines, yet lack other important components of these two systems.
      Other aspects of the archaeal translocation process appear specific to this
      domain, possibly related to the extreme environmental conditions in which archsea
      thrive. In the following, current understanding of archaeal protein translocation
      is reviewed, as is recent progress in reconstitution of the archaeal
      translocation process in vitro.

PMID- 15168609
TI  - The archaeal signal recognition particle: steps toward membrane binding.
AB  - Signal recognition particles and their receptors target ribosome nascent chain
      complexes of preproteins toward the protein translocation apparatus of the cell.
      The discovery of essential SRP components in the third urkingdom of the
      phylogenetic tree, the archaea (Woese, C. R., and Fox, G. E. (1977). Proc. Natl.
      Acad. Sci. U.S.A. 74, 5088-5090) raises questions concerning the structure and
      composition of the archaeal signal recognition particle as well as the functions
      that route nascent prepoly peptide chains to the membrane. Investigations of the
      archaeal SRP pathway could therefore identify novel aspects of this process not
      previously reported or unique to archaea when compared with the respective
      eukaryal and bacterial systems.

PMID- 15168610
TI  - The membrane-bound electron transport system of Methanosarcina species.
AB  - Members of the genus Methanosarcina are strictly anaerobic archaea that derive
      their metabolic energy from the conversion of a restricted number of substrates
      to methane. H2 + CO2 are converted to CH4 via the CO2-reducing pathway, while
      methanol and methylamines are metabolized by the methylotrophic pathway. Two
      novel electron transport systems are involved in the process of methanogenesis.
      Both systems are able to use a heterodisulfide as electron acceptor and either H2
      or F420H2 as electron acceptors and generate a proton-motive force by redox
      potential-driven H(+)-translocation. The H2:heterodisulfide oxidoreductase is
      composed of an F420-nonreducing hydrogenase and the heterodisulfide reductase.
      The latter protein is also part of the F420H2:heterodisulfide oxidoreductase
      system. The second component of this system is referred to as F420H2
      dehydrogenase. The archaeal protein is a homologue of complex I of the
      respiratory chain from bacteria and mitochondria. This review focuses on the
      biochemical and genetic characteristics of the three energy-transducing enzymes
      and on the mechanisms of ion translocation.

PMID- 15168611
TI  - Energy-converting [NiFe] hydrogenases from archaea and extremophiles: ancestors
      of complex I.
AB  - [NiFe] hydrogenases are well-characterized enzymes that have a key function in
      the H2 metabolism of various microorganisms. In the recent years a subfamily of
      [NiFe] hydrogenases with unique properties has been identified. The members of
      this family form multisubunit membrane-bound enzyme complexes composed of at
      least four hydrophilic and two integral membrane proteins. These six conserved
      subunits, which built the core of these hydrogenases, have closely related
      counterparts in energy-conserving NADH:quinone oxidoreductases (complex I).
      However, the reaction catalyzed by these hydrogenases differs significantly from
      the reaction catalyzed by complex I. For some of these hydrogenases the
      physiological role is to catalyze the reduction of H+ with electrons derived from
      reduced ferredoxins or poly-ferredoxins. This exergonic reaction is coupled to
      energy conservation by means of electron-transport phosphorylation. Other members
      of this hydrogenase family mainly function to provide the cell with reduced
      ferredoxin with H2 as electron donor in a reaction driven by reverse electron
      transport. As complex I these hydrogenases function as ion pumps and have
      therefore been designated as energy-converting [NiFe] hydrogenases.

PMID- 15168614
TI  - Rieske iron-sulfur proteins from extremophilic organisms.
AB  - Proteins located on the outside of the membranes of organisms thriving under
      extreme conditions like high or low pH, or high salinity face special challenges
      maintaining their structural integrity. This review is focused on the Rieske iron
      sulfur proteins from these organisms. Rieske proteins are essential subunits of
      the cytochrome bc-complexes, which are often of crucial importance for the energy
      metabolism of the cells. On the basis of the available data we propose strategies
      by which these proteins are able to stabilize their noncovalent bound cofactor
      and adapt to the function under extreme conditions.

PMID- 15168612
TI  - Dissimilatory oxidation and reduction of elemental sulfur in thermophilic
      archaea.
AB  - The oxidation and reduction of elemental sulfur and reduced inorganic sulfur
      species are some of the most important energy-yielding reactions for
      microorganisms living in volcanic hot springs, solfataras, and submarine
      hydrothermal vents, including both heterotrophic, mixotrophic, and
      chemolithoautotrophic, carbon dioxide-fixing species. Elemental sulfur is the
      electron donor in aerobic archaea like Acidianus and Sulfolobus. It is oxidized
      via sulfite and thiosulfate in a pathway involving both soluble and membrane
      bound enzymes. This pathway was recently found to be coupled to the aerobic
      respiratory chain, eliciting a link between sulfur oxidation and oxygen reduction
      at the level of the respiratory heme copper oxidase. In contrast, elemental
      sulfur is the electron acceptor in a short electron transport chain consisting of
      a membrane-bound hydrogenase and a sulfur reductase in (facultatively) anaerobic
      chemolithotrophic archaea Acidianus and Pyrodictium species. It is also the
      electron acceptor in organoheterotrophic anaerobic species like Pyrococcus and
      Thermococcus, however, an electron transport chain has not been described as yet.
      The current knowledge on the composition and properties of the aerobic and
      anaerobic pathways of dissimilatory elemental sulfur metabolism in thermophilic
      archaea is summarized in this contribution.

PMID- 15168613
TI  - Respiratory chains from aerobic thermophilic prokaryotes.
AB  - Thermophiles are organisms that grow optimally above 50 degrees C and up to
      approximately 120 degrees C. These extreme conditions must have led to specific
      characteristics of the cellular components. In this paper we extensively analyze
      the types of respiratory complexes from thermophilic aerobic prokaryotes. The
      different membrane-bound complexes so far characterized are described, and the
      genomic data available for thermophilic archaea and bacteria are analyzed. It is
      observed that no specific characteristics can be associated to thermophilicity as
      the different types of complexes I-IV are present randomly in thermophilic
      aerobic organisms, as well as in mesophiles. Rather, the extensive genomic
      analyses indicate that the differences concerning the several complexes are
      related to the organism phylogeny, i.e., to evolution and lateral gene transfer
      events.

PMID- 15168616
TI  - Proton-pumping inorganic pyrophosphatases in some archaea and other extremophilic
      prokaryotes.
AB  - Comparative studies between the proton-pumping, membrane-bound inorganic
      pyrophosphatases (H(+)-PPases) from hyperthermophilic and thermophilic
      prokaryotes and those from mesophilic organisms can now be performed because of
      very recent sequence data. Typical overall factors that contribute to protein
      thermostability are found in H(+)-PPases from extremophiles; nevertheless,
      putative active site motifs of this class of enzymes may be identical over the
      whole range of average growth temperatures of the compared prokaryotes.
      Heterologous expression in yeast of H(+)-PPases from organisms spanning a wide
      range of thermal habitats has allowed the biochemical comparison among these
      proteins within the same system, ensuring that differences observed are due to
      intrinsic characteristics of the proteins and not to their interactions with
      different cellular environments. On the other hand, the availability of H(+)
      PPase sequences from a variety of sources have permitted molecular phylogenetic
      studies of this class of proton pumps, thus providing information about their
      general structural and functional properties. A great step forward may be
      expected when one of the several groups now attempting crystallization and 3D
      structural determination of H(+)-PPases will be successful.

PMID- 15168615
TI  - An exceptional variability in the motor of archael A1A0 ATPases: from multimeric
      to monomeric rotors comprising 6-13 ion binding sites.
AB  - The motor domain of A1A0 ATPases is composed of only two subunits, the stator
      subunit I and the rotor subunit c. Recent studies on the molecular biology of the
      A0 domains revealed the surprising finding that the gene encoding subunit c
      underwent several multiplication events leading to rotor subunits comprising 2,
      3, or even 13 hairpin domains suggesting multimeric in different stoichiometry as
      well as monomeric rotors. The number of ion translocating groups per rotor ranges
      from 13 to 6. Furthermore, as deduced from the gene sequences H(+)-as well as
      Na(+)-driven rotors are found in archaea. Features previously thought to be
      distinctive for A0, F0 or V0 are all found in A0 suggesting that the differences
      encountered in the three classes of ATPases today emerged already very early in
      evolution. The extraordinary features and exceptional structural and functional
      variability in the rotor of A1A0 ATPases may have arisen as an adaptation to
      different cellular needs and the extreme physicochemical conditions in the early
      history of life.

PMID- 15168617
TI  - The archaeal P-type ATPases.
AB  - A phylogenetic analysis was carried out of a total of 58 P-type ATPases encoded
      within the genomes of 20 archaea species. Members from six subfamilies were
      identified including: putative metal-, proton-, calcium-, sodium/potassium-,
      potassium-, and magnesium/nickel-transporting ATPases. Six novel putative proton
      ATPases from archaea species growing under different temperature and pH
      conditions were shown to have shorter N- and C-termini than those of orthologous
      yeast or plant proton-ATPases. Moreover recent biochemical data are reviewed that
      report functional expression of putative archaea metal- or proton-ATPases in
      bacteria or yeast.

PMID- 15168618
TI  - Novel functional aspects of the membrane-bound exo-pyrophosphatase of the
      hyperthermoacidophilic archaeon Sulfolobus are provided by analysis of its gene
      and the adjacent gene cluster.
AB  - The gene of the previously described plasma-membrane-bound acidic pyrophosphatase
      (exo-PPase) and adjacent genes of the hyperthermoacidophilic crenarchaeon
      Sulfolobus acidocaldarius (DSM 639) were cloned and sequenced. The 4-kb gene
      cluster comprises four open reading frames (sepp, simp, sabc, and satr) encoding
      the pyrophosphatase, a small hydrophobic protein of unknown cellular function, a
      hydrophilic ABC transport ATPase, and an amino transferase. The four proteins
      have deduced molecular masses of 21, 16, 34, and 48 kDa, respectively. Sepp,
      simp, and sabc are transcribed as monocistronic mRNAs from which sepp and sabc
      have been heterologously expressed by in vitro translation using reticulocyte
      lysates. The Sulfolobus acidocaldarius acidic exo-pyrophosphatase is a membrane
      residing protein anchored with five transmembrane alpha-helices. Alignments with
      protein sequences from databases together with predictions of membrane topology
      reveal a novel group of proteins with the conserved phosphatase motif KxxxxxRP
      (x12-54)-PSGH-(x31-54)-SRxxxxxHxxxD. For none of them a phosphatase or
      pyrophosphatase activity has yet been described except for the authentic
      Sulfolobus acidocaldarius protein. On the basis of these investigations a direct
      role of the exo-PPase in dolichyl phosphate or pyrophosphate hydrolysis and in
      resistance to the peptide antibiotic bacitracin is discussed.

PMID- 15168620
TI  - Characteristics of female sex workers and their HIV/AIDS/STI knowledge, attitudes
      and behaviour in semi-urban areas in South Africa.
AB  - The aim of this study was to investigate characteristics of female sex workers
      and their HIV/AIDS/STI knowledge, attitudes and behaviour in semi-urban areas in
      South Africa. The sample included 70 female sex workers from the Tzaneen and
      Phalaborwa area in the Limpopo Province. A modified form of snowball sampling
      known as "targeted" sampling was used for identifying female sex workers. Results
      showed an inadequate knowledge of HIV prevention methods and some incorrect
      beliefs about AIDS transmission. Most sex workers reported condom use with their
      last sex client, inconsistent condom use with paying partners, and had poor
      condom use with regular partners. One third were drinking alcohol daily, one
      quarter had had voluntary HIV tests, and three quarters had been exposed to HIV
      interventions. Findings are discussed and implications for HIV interventions
      outlined.

PMID- 15168619
TI  - Expression, isolation, and crystallization of the catalytic domain of CopB, a
      putative copper transporting ATPase from the thermoacidophilic archaeon
      Sulfolobus solfataricus.
AB  - The P-type CPX-ATPases are responsible for the transport of heavy metal ions in
      archaea, bacteria, and eukaryotes. We have chosen one of the two CPX-ATPases of
      the thermophile Sulfolobus solfataricus, CopB (= SSO2896) for the investigation
      of the molecular mechanism of this integral membrane protein. We recombinately
      expressed three different soluble domains of this protein (named CopB-A, CopB-B,
      and CopB-C) in Escherichia coli and purified them to homogeneity. 3D crystals of
      CopB-B, the 29 kDa catalytic ATP binding/phosphorylation domain were produced,
      which diffracted to a resolution of 2.2 A. CopB-B has heavy metal stimulated
      phosphatase activity, which was half maximal in the presence of 80 microM Cu2+.
      The protein forms a phosphorylated intermediate with the substrate gamma-(32P)
      ATP. No specific activation of the polypeptide was observed, when CopB-B
      phosphatase activity was tested in the presence of the purified CopB-C and CopB-A
      proteins, which provide the cation binding and the phosphatase domains. We
      conclude that CopB is a putatively copper translocating ATPase, in which
      structural elements integrally located in the membrane are required for full,
      coordinated activation of the catalytic ATP binding domain.

PMID- 15168621
TI  - The relationship between adolescent depressive symptomology and substance abuse.
AB  - The research aimed to investigate the phenomena of adolescent depressive
      symptomology, substance abuse and the relationship between the two phenomena in a
      South African context. The influence of moderator variables was also examined.
      Another objective was to determine risk factors for the before mentioned. This
      was done by using a questionnaire with a sample of 1298 conveniently selected
      adolescents in a South African high school. It was determined that adolescents
      become progressively unhappier from 13 to 17 years of age. Girls are more
      depressed than boys. This research also revealed that adolescent depressive
      symptomology is significantly and positively correlated with earlier age of onset
      of substance abuse as well as frequency of usage. There appear to be no gender
      differences in substance abuse but teenagers from different ethnic and language
      groups differ in their use of substances. Risk factors for depression and
      substance abuse included a conflict relationship with parents, the experience of
      major stressful events, dissatisfaction with school grades and friends' use of
      substances.

PMID- 15168622
TI  - Integrated reproductive health services: the perspectives of providers.
AB  - With the advent of the AIDS epidemic the focus of family planning programmes has
      shifted from an emphasis on pregnancy prevention to include disease prevention.
      The move towards integration has meant a major re-orientation in the role of
      health providers. This article seeks to expand knowledge about the implementation
      of integrated services from the perspective of providers. It focuses more
      specifically on the provider's perceptions and experiences of integrated
      services. A range of methods is used to obtain information from providers,
      including an inventory of health facilities, in-depth interviews and focus group
      discussions. The results suggest that the majority of providers expressed
      favourable attitudes to integrated services. Integrated services are seen as a
      more client centred approach. However, there is a lack of clarity about the
      precise from that integration should take. As a result, providers seem more
      comfortable with the traditional focus on family planning and maternal and child
      health than sexually transmitted infections.

PMID- 15168623
TI  - The educational and supportive needs of informal caregivers working at Refentse
      Clinic, Hammanskraal.
AB  - Informal caregivers have long been used as health care providers. It is also not
      uncommon in present days, to see such practice in the community. This practice of
      caring normally occurs within the context of the family. The purpose of the study
      is to explore and describe the educational and supportive needs of informal
      caregivers. This will assist in planning and establishing health education
      programmes and a supportive network, for the informal caregivers at Refentse
      clinic, at Hammanskraal. A qualitative, explorative and descriptive design was
      followed, to collect the data. Participants in this study were informal
      caregivers, who were involved in Refentse clinic and resided in Stinkwater
      village. The method of choice, to gather data, was focus groups. An unstructured
      interview with a schedule was followed. Tesch's method was used, to analyse the
      data. The results indicated that the informal caregivers' educational needs were
      mostly concentrated on health promotion and disease prevention activities. Their
      needs concerning support, mainly concentrated around support from government, the
      community, the University and the Primary Health Care clinic, in the area where
      they are serving. Personal needs focussed on recognition and respect.

PMID- 15168624
TI  - The knowledge and attitudes of traditional birth attendants towards HIV/AIDS and
      their beliefs related to perinatal care: a study conducted in KwaZulu Natal.
AB  - Traditional birth attendants (TBAs) are still mainly being utilized in the rural
      areas even in the presence of the formal health care facilities. Studies reveal
      that the utilization of TBAs is beneficial in some other contexts with some
      support and supervision from the western health sector. In order to develop
      further training for TBAs the researchers deemed it necessary to assess their
      knowledge, attitudes and beliefs related to HIV/AIDS, prenatal care, delivery and
      postnatal care. This was a survey of an identified group of TBAs who had already
      received some training and were currently practicing in the catchment areas. Five
      Primary health care (PHC) clinics from Abaqulusi sub-district in Zululand Health
      District, Kwa-Zulu Natal Province, were selected as sites for the focus groups. A
      total of 57 TBAs participated in focus groups and completed a questionnaire. The
      HIV/AIDS knowledge questionnaire consisted of 16 questions about transmission,
      symptoms, course of the disease and its risk factors. An assessment tool was used
      to assess attitudes, beliefs and practice in relation to pregnancy, delivery and
      postnatal care. The results of this study demonstrated that the TBAs have a good
      knowledge of what they are doing.

PMID- 15168626
TI  - Knowledge, beliefs and attitudes of community health workers about hypertension
      in the Cape Peninsula, South Africa.
AB  - This article explores the perceptions and attitudes of community health workers
      (CHWs) about hypertension. The level of knowledge of hypertension, as well as
      their personal attitude towards this is crucial in the style and quality of their
      interventions. CHWs, whose role in health promotion is being increasingly
      recognised, can help contain or reduce the prevalence of hypertension by
      influencing the community to adopt healthy lifestyles. Forty-three CHWs employed
      by Zanempilo in two study areas, Sites B and C in Khayelitsha in the Cape
      Peninsula, South Africa, were included in the study. Firstly, focus group
      discussions were conduced with 17 purposively selected CHWs to explore attitudes,
      beliefs and perceptions of hypertension. Secondly, interviews were conducted to
      assess their basic knowledge about causes, prevention and control of
      hypertension. The focus group discussions revealed that CHWs were uncertain about
      the causes of hypertension. They also found it difficult to grasp the fact that
      people without risk factors, such as overweight or a family history of
      hypertension, could be hypertensive. Many CHWs believe in traditional medicines
      and home-brewed beer as the best treatment for hypertension. They believe that
      people who take medical treatment become sicker and that their health
      deteriorates rapidly. Risk factors of hypertension mentioned during the
      structured interviews include inheritance, lack of physical activity, consuming
      lots of salty and fatty food. Conclusions drawn from the findings of the CHWs'
      responses highlighted their insufficient knowledge about hypertension as a
      chronic disease of lifestyle. Meanwhile they are expected to play a role in
      stimulating community residents' interest in the broad principle of preventive
      health maintenance and follow-up. Data obtained from this research can be used
      for the planning of health-promotion programmes. These should include preventing
      hypertension and improving primary management of individual sufferers. Because of
      their working relations and close link with CHWs, community nurses in primary
      health-care facilities need to recognise these beliefs and attitudes since these
      may differ from their own.

PMID- 15168625
TI  - Cultural health practices of South African Vatsonga people on the home care of
      children with measles.
AB  - The purpose of this research study was to identify the cultural health practices
      of the Vatsonga in relation to the home care of children with measles. It was
      undertaken in the Giyani District of the Limpopo Province, in the Republic of
      South Africa. The qualitative, explorative and contextual design was used to
      conduct this project. Data was collected from nine key informants and nineteen
      general informants. Data was collected using individual interviews with key
      informants and focus group interviews with general informants. Observations were
      also made. The findings revealed that the Vatsonga still provide home care for
      children with measles. Those who care for the sick children are women--either the
      mother of the sick child or an elderly woman with knowledge of the disease. There
      are different cultural practices that the Vatsonga observe when there is a child
      suffering from measles. These include isolation of the child, restriction of
      sexual intercourse, giving of a milk diet to the sick child and performance of a
      cultural ceremony at the resolution of the disease. Similarities and differences
      between hospital and home-based care were identified. Recommendations were made
      using Leininger's three modes of decision making as explained in the Sunrise
      Model, which include the following: cultural care preservation of maintenance;
      cultural care accommodation or negotiation; cultural care repatterning or
      restructuring.

PMID- 15168627
TI  - Health-service utilization by pregnant women in the greater Mafikeng-Mmabatho
      district.
AB  - Since the implementation of free maternity services in South Africa from 1994,
      more maternity services were provided (SA, 1994: 73). These services are however
      inaccessible to many pregnant women in the rural areas, leading to sub-optimal
      antenatal health service utilization. Another problem that emerged, is
      deterioration in antenatal health service rendering throughout the country, as
      well as a lack of guidelines for the mobilization of pregnant women in order to
      promote optimal antenatal health service utilization (ANHSU) in the North West
      Province. The mentioned problems were the reasons for undertaking this research.
      The aims formulated for this research were: To determine the composition of the
      infrastructure of the antenatal health services and the efficacy of the antenatal
      health-service rendering in the greater Mafikeng-Mmabatho District; To undertake
      a survey of the ANHSU by pregnant women attending the mentioned services; To
      explore and describe the perceptions of these pregnant women regarding ANHSU; To
      formulate recommendations for antenatal health service providers working in the
      greater Mafikeng-Mmabatho District for the mobilization of pregnant women to
      promote optimal ANHSU. A qualitative survey design was followed within the
      context of the greater Mafikeng-Mmabatho District in the North West Province.
      Data-collection was managed through completion of structured questionnaires by
      chief professional nurses and puerperal women and by holding semi-structured
      interviews with puerperal women who were selected using non-probable, voluntary
      and purposive sampling. The findings that emerged were, that the composition of
      the infrastructure of the majority antenatal health services in the greater
      Mafikeng-Mmabatho District were insufficiently equipped indicating the provision
      of ineffective antenatal health service rendering. Pregnant women were utilizing
      the antenatal health services sub-optimally and the exploration and description
      of their ANHSU, revealed factors promoting and preventing utilization.
      Recommendations have been formulated for nursing education, nursing research and
      nursing practice with specific reference to the formulation of guidelines for
      antenatal health service providers to promote optimal ANHSU by pregnant women.

PMID- 15168629
TI  - The global burden of trachoma.

PMID- 15168628
TI  - Evaluation of clinical teaching and professional development in a problem- and
      community-based nursing module.
AB  - In South Africa the main focus is on primary health care. This affects the
      education and training of nurses, and training schools must respond by developing
      appropriate teaching modules. A school of nursing developed, implemented and
      revised a problem- and community-based learning module over a period of three
      years (1996-1998). This student-centered module focuses on students' needs,
      active participation, collaboration, accountability, self-assessment, self-study,
      life-long learning and appropriate skills. In the formal clinical teaching
      environment PBL was the main approach. However, this approach was also supported
      by a variety of strategies, for example group discussions and scenarios. The
      knowledge, attitudes and professional development skills acquired in the PBL
      approach were then applied informally in the community setting (CBE). The purpose
      of the study was to evaluate a first year clinical teaching module as part of an
      extensive programme. A quantitative research method, a descriptive design, and a
      variety of data collection techniques were used. Conclusions were that clinical
      teaching was effective within the problem- (PBL) and community-based (CBE)
      approaches; 78% of respondents were positive about the clinical learning
      environment; 61% stated that expectations were met; 81% preferred group
      activities, and 67% indicated that they had developed professional skills.
      Facilitators agreed that clinical teaching met the requirements of PBL & CBE. The
      pass rate also improved.

PMID- 15168630
TI  - Atrial fibrillation and flutter: overview.

PMID- 15168631
TI  - Acute management of atrial fibrillation.

PMID- 15168632
TI  - Direct current cardioversion for atrial fibrillation and flutter.

PMID- 15168633
TI  - Anticoagulation in atrial fibrillation.
AB  - Anticoagulation with warfarin is the most effective means of reducing stroke in
      AF. The generally recommended INR goal is 2-3. Aspirin provides a modest degree
      of stroke protection in AF but is inferior to warfarin. Assessment of stroke risk
      is critical in determining whether to prescribe warfarin therapy to a patient
      with AF. The most important risk factors for stroke in AF are age over 65 years,
      hypertension, prior stroke, and left ventricular dysfunction or heart failure.
      The risk of warfarin may be less than commonly believed, but increases when
      warfarin is combined with aspirin. Patients with paroxysmal AF are not at lower
      risk of stroke than those with persistent AF and should be treated with warfarin.
      Apparently successful therapy with antiarrhythmic agents does not eliminate the
      need for anticoagulation. New antithrombotic therapies are being studied and may
      soon provide an alternative to warfarin.

PMID- 15168634
TI  - Nonpharmacologic therapy for atrial fibrillation and flutter.

PMID- 15168636
TI  - Unique aspects of atrial fibrillation: coexistence with other arrhythmias
      tachycardia-induced cardiomyopathy.

PMID- 15168635
TI  - Chronic pharmacologic therapy for atrial fibrillation and flutter.

PMID- 15168637
TI  - Mammography rates among women with Medicare in Rhode Island are low and not
      improving.

PMID- 15168638
TI  - Inpatient care for severe trauma in Rhode Island.

PMID- 15168640
TI  - The polysyllabic worm.

PMID- 15168639
TI  - Miriam Hospital Morbidity and Mortality Conference, a case of chest pain.

PMID- 15168641
TI  - Belt tightening hurts LTC staffing.

PMID- 15168642
TI  - Better training leads to better care.

PMID- 15168643
TI  - Building on patient-based software. Interview by Marla Fern Gold.

PMID- 15168644
TI  - Promoting safety, reducing falls.

PMID- 15168645
TI  - A dispute resolution alternative.

PMID- 15168646
TI  - LTC debt financing strategies.

PMID- 15168647
TI  - [Stepwise uterine devascularization in postpartum hemorrhages].
AB  - The authors reported the results from a retrospective investigation of 10121
      deliveries for a three-year period (1981-1983) as well as from a prospective
      study of 6239 child-births during a three-year period after a 20-year-long time
      lag, i.e., in 2000-2002. The cases with early post-partum hemorrhages (EPH) and
      with accomplished laparotomy were examined. The causes for EPH, the obstetric
      therapeutic measures and manipulations prior to the laparotomy as well as the
      surgical interventions after opening the abdomen were considered. The authors
      emphasized that 20 years ago three uteri only could be "saved" by means of
      ligation of the uterine vessels. A hysterectomy was carried out in 21 cases with
      massive EPH after the laparotomy. After two decades the situation changed
      dramatically. The hysterectomies amounted to only 22.22% of the cases (n = 4)
      while in the rest females (n = 14) the copying of the massive hemorrhages was
      performed by means either of stepwise ligation of the uterine vessels, or of
      ligation of the hypogastric ones in 3 cases with additional vaginal lacerations.
      It was outlined that mother's mortality rate was zero during these two periods.
      The conclusion has been drawn that the ligation of the uterine vessels represents
      an alternative to the hysterectomy when copying the EPH and preserves the child
      bearing functions of some females because of the subsequent vascular
      recanalization.

PMID- 15168648
TI  - [Use of recombinant factor VIIa for the control of massive bleeding caused by
      uterine hypotonia in post-placental period].
AB  - We report our clinical opinion for recombinant activated factor VII (NovoSeven,
      Novo Nordisk, Copenhagen, Denmark) administration in puerperae with massive
      haemorrhage caused by uterine hypotonia. Four women with severe bleeding in post
      placental period received NovoSeven in bolus IV. The blood loss and laboratory
      changes in hematology and haemostasis parameters are monitored. The right time of
      application and the mean effective dose of the medication are discussed. The
      bleeding was ceased in all cases. Decrease in values of Hb, Er and PTT was noted.
      The mean administered dose of 72 micrograms/kg BW was effective. The laboratory
      values showed tendency for improvement on the 24 hour after administration and
      normal levels on discharge. The use of recombinant factor VIIA in puerperae with
      severe bleeding in the postplacental period is effective and safe enough and
      could be an alternative to the extreme surgical procedures.

PMID- 15168649
TI  - [Comparative study of itraconazole and fluconazole therapy in vaginal
      candidosis].
AB  - Women who had symptomatic acute vulvovaginal candidiasis are include in this
      study. Micological investigation is realized by microscopy, culture method (CHROM
      agar, BD, USA) and ID 32 C (Fungus), Mini API Bio Merieux, France. Most frequent
      isolates are Candida albicans (82.67%), followed by C. glabrata (7.8%) and C.
      parapsilosis (5.51%). We compare two groups of patients: received itraconazole
      (200 mg bd oral dose for 1 day) and fluconazole (150 mg single oral dose). The
      rate of mycological cure is 93.8% in the itraconazole group and 79.03% in the
      fluconazole group (p = 0.008). Clinical response rate for women receiving
      itraconazole (80%) is significantly higher than fluconazole group (59.7%). These
      results suggests that itraconazole is more effective than fluconazole in the
      treatment of acute vulvovaginal candidiasis.

PMID- 15168650
TI  - [Potentialities of immunodiagnostics in endometriosis].
AB  - In this study, the authors tried to figure out the value of immunodiagnostics,
      and especially the protein characteristics of the peritoneal fluid in women with
      endometriosis. The main purpose was to establish whether this kind of diagnostics
      is reliable enough for clinical purposes.

PMID- 15168651
TI  - [Emergency contraception with levonorgestrel for teenagers--efficacy,
      tolerability, and level of information awareness].
AB  - OBJECTIVE: Assessment of efficacy and side effects of emergency contraception for
      teenagers with levonorgestrel (LNG) and the level of users' informedness about
      possibilities and practical application. METHODS: The subjects are healthy girls
      (n = 49) with regular menstrual cycles at the age between 15 and 19, having had
      one unprotected or faultily protected sexual intercourse. All of them have
      administered 0.75 mg LNG within the 72nd hour, repeated after 12 hours. The data
      have been processed by variational analysis. RESULTS: One pregnancy was
      registered of a girl with firstintake at the 67th hour - pregnancy rate - 2,0%.
      The most frequent side effect was nausea - 26,5%, folowed by breast tenderness -
      22,4% and fatigue - 20,4%. An up to 7th day delay in menstrual cycle is non
      significantly more frequent - 14,3%, followed by a delay of  more than 7 days
      breakthrough bleeding - 8,2%. No significant changes were established in the
      lenght of the menstrual cycle. Emergency contraception is sought for after
      unprotected sexual intercourse in 69,4%, and condom failure problems in 30,6%.
      Only 18,4% have sufficient information about the possibilities and practical use
      of emergency contraception. CONCLUSION: LNG provides effective, highly tolerable
      contraception with a small number of side effects. Need is felt for serious
      popularization of the application of emergency contraception with teenagers.

PMID- 15168652
TI  - [Vaginal sonography as a method for examination of women with pre- and
      postmenopausal bleeding].
AB  - At present time abrasio probatoria of the cavum uteri is a method of choice in
      diagnostic of the endometrial pathology.

PMID- 15168653
TI  - [Antiphospholipid syndrome and pregnancy].
AB  - The antiphospholipid antibody syndrome (APLS) is multisystem, autoimmune disease,
      which is characterized by: thrombosis, obstetrics complications and
      thrombocytopenia. The two most clinically significant antiphospholipid antibodies
      (APLa) that are associated with recurrent pregnancy loss and thrombosis are
      anticardiolipin antibodies (ACL) and lupus anticoagulant (LA). The laboratory
      diagnosis is based on the presence of moderate to high positive ACL and/or LA.
      The inhibitory effect of antiphospholipid antibodies /APLa/ on trophoblast
      intercellular fusion, hormone production and invasion may cause pregnancy loss.
      Once placentation is established their thrombogenic action leads to decreased
      placental perfusion and subsequent infarction. The APLa--mediated inhibition of
      trophoblastic invasion and APLa--mediated vasculopathy in the placental bed
      arteries result in abnormal uterine artery /UA/ Doppler waveforms. The
      association between APLa and high resistance index /RI/ and/or diastolic notch
      /DN/ in the Doppler waveforms is high predictive for adverse pregnancy outcome,
      including pre-eclampsia/eclampsia, intrauterine growth retardation, placental
      abruption, intrauterine fetal death. Maternal treatment and careful monitoring of
      fetal well-being are mandatory in the management of these high-risk pregnancies.

PMID- 15168655
TI  - [Neoadjuvant intraarterial chemotherapy in uterine cervix cancer].

PMID- 15168654
TI  - [Screening for chromosomal anomalies of the fetus between 11-14 gestational
      weeks. Review of literature].
AB  - The aim of the review is to provide an up-to-date overview of the possibilities
      for prenatal screening for chromosomal fetal anomalies between 11-14 weeks of
      gestation. A specific ultrasound marker in the first trimester, known as fetal
      nuchal transluceny [NT], is described. The usefulness of fetal NT as a screening
      tool for chromosomal anomalies, some structural anomalies, rare genetic syndromes
      and adverse pregnancy outcome is discussed.

PMID- 15168657
TI  - [The case of secondary abdominal pregnancy in 14th week of gestation].
AB  - The authors report on a rare case of secondary abdominal pregnancy after tubal
      rupture of a 40-year-old woman.

PMID- 15168658
TI  - [Risk and benefits of using contraceptives of third generation].

PMID- 15168656
TI  - [The case of diagnostic difficulties of submucous myoma in early pregnancy].
AB  - The authors describe observed case of pregnancy and degenerative submucous myoma.
      Diagnostic difficulties.

PMID- 15168659
TI  - [Effect of antioxidants in women with increased risk of preeclampsia. The role of
      oxidative stress in preeclampsia].
AB  - New frontiers have been opened lately in the understanding of the patho
      phisiology of preeclampsia thus giving new directions in the process of therapy
      of this condition. Oxidative stress is a condition characterized by peroxidants
      predominating over antioxidants. Numerous intensive studies are carried out to
      reveal the role of oxidative stress in the pathogenesis of preeclampsia.

PMID- 15168661
TI  - [On the surgery of heart. 1898].

PMID- 15168660
TI  - Role of VLDL receptor in the process of foam cell formation.
AB  - The role of very low density lipoprotein receptor (LVLDR) in the process of foam
      cell formation was investigated. After the primary cultured mouse peritoneal
      macrophages were incubated with VLDL, beta-VLDL or low density lipoprotein (LDL),
      respectively for 24 h and 48 h, foam cells formation was identified by oil red O
      staining and cellular contents of triglyceride (TG) and total cholesterol (TC)
      were determined. The mRNA levels of LDLR, LDLR related protein (ILRP) and VLDLR
      were detected by semi-quantitative RT-PCR. The results demonstrated that VLDL,
      beta-VLDL and LDL could increase the contents of TG and TC in macrophages. Cells
      treated with VLDL or beta-VLDL showed markedly increased expression of VLDLR and
      decreased expression of LDLR, whereas LRP was up-regulated slightly. For
      identifying the effect of VLDL receptor on cellular lipid accumulation, ldl-A7-VR
      cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was
      used to incubate with lipoproteins for further examination. The results
      elucidated that the uptake of triglyceride-rich lipoprotein mediated by VLDLR
      plays an important role in accumulation of lipid and the formation of foam cells.

PMID- 15168663
TI  - An educational imperative: The role of ethical codes and normative prohibitions
      in CBW-Applicable research.
AB  - This paper examines the role of ethics in research with potential applicability
      to chemical and biological warfare. If focuses upon biological warfare research,
      and examines the ethical dilemmas faced by those working with dual-use potential
      technologies. It discusses the normative, legal and ethical prohibitions against
      participation in chemical and biological warfare programmes from a Western
      perspective. It examines the motivations of individuals participating in CBW
      research and concludes with recommendations for increasing awareness about
      ethical and normative prohibitions. An appendix lists the results of a survey of
      ethical codes in relevant scientific disciplines conducted via the Internet.

PMID- 15168662
TI  - Ethics of university research, biotechnology and potential military spin-off.
AB  - The paper provides a brief introduction to the biotechnology revolution and its
      impact upon biological research relevant to military uses. It describes the
      status of biological weapon today, and current efforts to strengthen the
      Biological Weapons Convention with a legally binding compliance protocol.
      Specific modifications of micro-organisms that may be of military use are
      discussed. There examples of dual-use research activities are then used to
      highlight issues and dilemmas in ethical decision making.

PMID- 15168664
TI  - Killing 'without the distressing preliminaries': Scientists' defence of the
      British biological warfare programme.
AB  - This article presents historical cases in which British scientists, principally
      scientific advisors, have attempted to defend research on biological weapons.
      Although the historical record is scant, there is a degree of continuity in their
      justifications, and a number of themes can be identified. It was argued, that
      biological weapons research is morally justified because it produces humane
      weapons; that it is no different from medical or other research; and that is
      being performed for defensive purposes. It is argued that this defence is
      directed primarily towards other scientists working on germ warfare, and was
      formed part of the 'moral economy' of that secret community.

PMID- 15168665
TI  - The role of professionals in the South African chemical and biological warfare
      programme.
AB  - This paper provides a short account of the South African Defence Force's chemical
      and biological warfare programme during apartheid, specifically during the period
      1980 to 1994. It examines the circumstances of recruitment of the scientists and
      physicians and their retention in the programme; details the 'scientific efforts'
      of the programme and its aberrations; and explores ethical issues in relation to
      the involvement of scientists in the programme.

PMID- 15168666
TI  - Eugenics and individual phenotypic variation: to what extent is biology a
      predictive science?
AB  - Eugenics, in whatever form it may be articulated, is based on the idea that
      phenotypic characteristics of particular individuals can be predicted in advance.
      This paper argues that biology's capacity to predict many of the characteristics
      exhibited by an individual, especially behavioral or cognitive attributes, will
      always be very limited. This stems from intrinsic limitations to the methodology
      for relating genotypes to phenotypes, and from the nature of developmental
      processes which intervene between genotypes and phenotypes. While genetic studies
      may generate valid population predictions for conditions which impact human
      health, neither genetics nor developmental biology are likely to generate useful
      individual predictions about variation in non-disease-related human behavioral
      and cognitive phenotypes in the foreseeable future.

PMID- 15168667
TI  - Genes for human personality traits.
AB  - This article considers three major problems with the concept of genes for human
      personality traits: (1) uncertainty about what human personality is; (2) what we
      mean when we say there is a gene "for" a mental attribute; and (3) the complexity
      of interactions between genes and environment, and among the genes themselves. It
      then draws on examples from empirical human genetic studies by the author and his
      colleagues in order to suggest that the concept of genes for human personality
      traits nevertheless does have some validity, and also that we may be on the brink
      of discovering genes with major effects on human personality. This possibility,
      in particular its ethical aspects, has aroused some public concern. It is
      suggested that confidential information about an individual's genes does not
      differ in principle from other confidential information about him or her, and
      that the ability (currently theoretical) to affect genes and their expression,
      temporarily or permanently, does not differ ethically from our current ability to
      affect other aspects of an individual's physical and psychological functioning.
      Genes for potential offspring, contained in ova and sperm cells, constitute a
      special case.

PMID- 15168668
TI  - The complexity of the genotype-phenotype relationship and the limitations of
      using genetic "markers" at the individual level.
AB  - Many associations have recently been discovered between phenotypic variation and
      genetic loci, causing some to advocate what Robert Sinsheimer has called "a new
      eugenics" that would treat genetic "defects" in individuals prone to a disease.
      The first premise of this vision is that genetic association studies reveal the
      biological cause of the phenotypic variation. Once the responsible genes are
      known, the second premise is that we should focus upon changing "nature" rather
      than "nurture" by correcting the "defective" genes. The first premise is flawed
      because associations between genetic markers and phenotypes can be spurious, as
      shown by an example. Moreover, it is shown that using non-causative but
      associated genetic markers one at a time (the normal practice) can lead to
      incorrect predictions of disease risk for many individuals. Going from
      association to causation is a non-trivial step scientifically that has rarely
      been done in much of the human genetic research. Even when a particular locus
      does contribute to the phenotypic variation of interest, the first premise
      remains flawed because phenotypes in general arise from complex interactions
      among genes and between genes and environments as shown for genes associations
      with coronary artery disease (CAD). The ability of current molecular genetic
      tools to "fix" defective genotypes is extremely limited, but even if the
      technological problems could be overcome, the studies on CAD reveal no obvious
      "defective" gene to fix because the genetic effects are so context dependent
      (upon both other genes and environmental factors). Contrary to the second premise
      of the new eugenics, the more we learn about how different genotypes show
      variable responses to environments, the more important the environment becomes
      for individual treatment. The paradigm of a "defective gene" may work for
      classical Mendelian genetic diseases that are due to loss-of-function mutations.
      However, such mutations affect only a small portion of humanity. When the focus
      is changed to common disease and behavioral phenotypes, the "defective gene"
      paradigm is biologically meaningless and often harmful when applied to
      individuals. Thus, even when genes clearly do influence common phenotypic
      variation, the premises of the "new eugenics" are biologically indefensible.

PMID- 15168669
TI  - Lowering the burden of hereditary diseases in a traditional, inbred community:
      ethical aspects of genetic research and its application.
AB  - The remarkable progress in modern genetic technology enables the identification
      of genes causing devastating diseases and thereby the development of tools for
      prenatal diagnosis and carrier detection. To implement the results of genetic
      research in traditional societies, where genetic diseases are more prevalent due
      to inbreeding, necessitates a culturally appropriate approach that also promotes
      traditional and societal values important to the relevant community. This paper
      presents our experience with implementing the results of modern genetic research
      among the traditional community of the Negev Bedouin of Israel. Although the
      benefit of using those results for the prevention of genetic diseases seems
      obvious, successful implementation relies on a carefully designed educational
      program aimed at changing culturally related attitudes and perceptions. Such a
      program should attend to the needs of the community and be sensitive to its
      traditional values.

PMID- 15168670
TI  - Eugenics and genetic testing.
AB  - Pressures to lower health-care costs remain an important stimulus to eugenic
      approaches. Prenatal diagnosis followed by abortion of affected fetuses has
      replaced sterilization as the major eugenic technique. Voluntary acceptance has
      replaced coercion, but subtle pressures undermine personal autonomy. The failure
      of the old eugenics to accurately predict who will have affected offspring
      virtually disappears when prenatal diagnosis is used to predict Mendelian
      disorders. However, when prenatal diagnosis is used to detect inherited
      susceptibilities to adult-onset, common, complex disorders, considerable
      uncertainty is inherent in the prediction. Intolerance and the resurgence of
      genetic determinism are current pressures for a eugenic approach. The increasing
      use of carrier screening (to identify those at risk of having affected offspring)
      and of prenatal diagnosis could itself generate intolerance for those who refuse
      the procedures. Genetic determinism deflects society from social action that
      would reduce the burden of disease far more than even the maximum use of
      eugenics.

PMID- 15168671
TI  - Ethical aspects of genetic screening in Israel.
AB  - Advances in genetic research make it possible to identify carriers of a growing
      number of genetic diseases. The World Health Organization (WHO) published several
      preconditions for community carrier screening. This paper aims to present some of
      the dilemmas about screening in Israel and the difficulties in following the
      WHO's helpful criteria. Some of the genetic diseases that are rare in the world
      are relatively common among several communities in Israel, and one of the
      dilemmas is for which of them screening is justified. Consensus exists among
      professionals and among the public about screening for a severe disease like Tay
      Sachs, but the justification for screening for a disease with a widely variable
      expression, like Gaucher disease, is debatable. Another dilemma is whether to
      offer screening to the general population when the options to solve the problem
      are still not clear, as is the case of screening for carriers of BRCA1 and BRCA2.
      The author also explains why geneticists in Israel cooperate with a screening
      program in the ultra-orthodox community, although it is done according to unusual
      rules.

PMID- 15168672
TI  - Eugenic considerations in the theory and practice of genetic counseling.
AB  - Is genetic counseling a form of eugenics? To some extent, the answer depends upon
      how the terms "eugenics" and "genetic counseling" are defined. This paper reviews
      the eugenic implications of four models of genetic counseling. The complexities
      of slapping the eugenic label on genetic counseling are illustrated with three
      cases drawn from clinical practice. However, even though genetic counseling is
      not always a eugenic activity, genetic counselors work in a medical/financial
      setting that has the net eugenic effect of, and profits from, reducing the number
      of people with genetic disorders.

PMID- 15168673
TI  - Negative and positive genetic interventions: is there a moral boundary?
AB  - Some have claimed that negative genetic interventions are morally permissible
      while positive ones are not, but the distinction cannot be used to draw this
      moral boundary. Underlying the negative/positive distinction is a distinction
      between treatment and enhancement. The treatment/enhancement distinction at best
      provides an imperfect guide to which health care services we are obliged to
      provide and which we are not. It offers only some "warning flags" to help us
      think about what is permissible or not.

PMID- 15168674
TI  - Can genetic counseling avoid the charge of eugenics?
AB  - The claim that x is a form of eugenics is frequently used as if it were a
      knockdown argument against x. Genetic counseling has tried to distance itself
      from eugenics by presenting itself as facilitating choice. Its success in this
      attempt has been challenged. The argument however is not a knockdown one and
      there is scope for some mediation between autonomy and public health goals in
      genetics.

PMID- 15168675
TI  - Genetic services, economics, and eugenics.
AB  - What are the aims of genetic services? Do any of these aims deserve to be labeled
      "eugenics"? Answers to these strenuously debated questions depend not just on the
      facts about genetic testing and screening but also on what is understood by
      "eugenics," a term with multiple and contested meanings. This paper explores the
      impact of efforts to label genetic services "eugenics" and argues that attempts
      to protect against the charge have seriously distorted discussion about their
      purpose(s). Following Ruth Chadwick, I argue that the existence of genetic
      services presupposes that genetic disease is undesirable and that means should be
      offered to reduce it. I further argue that the economic cost of such disease is
      one reason why governments and health care providers deem such services
      worthwhile. The important question is not whether such cost considerations
      constitute "eugenics," but whether they foster practices that are undesirable
      and, if so, what to do about them The wielding of the term "eugenics" as a weapon
      in a war over the expansion of genetic services, conjoined with efforts to
      dissociate such services from the abortion controversy, has produced a rhetoric
      about the aims of these services that is increasingly divorced from reality.
      Candor about these aims is a sine qua non of any useful debate over the
      legitimacy of the methods used to advance them.

PMID- 15168676
TI  - Eugenics is alive and well: a survey of genetic professionals around the world.
AB  - A survey of 2901 genetics professionals in 36 nations suggests that eugenic
      thought underlies their perceptions of the goals of genetics and that
      directiveness in counseling after prenatal diagnosis leads to individual
      decisions based on pessimistically biased information, especially in developing
      nations of Asia and Eastern Europe. The "non-directive counseling" found in
      English-speaking nations is an aberration from the rest of the world. Most
      geneticists, except in China, rejected government involvement in premarital
      testing or sterilization, but most also held a pessimistic view of persons with
      genetic disabilities. Individual, but not state-coerced, eugenics survives in
      much modern genetic practice.

PMID- 15168677
TI  - Eugenics in Japan: some ironies of modernity, 1883-1945.
AB  - Japanese eugenic discourse and institution building contrast sharply with
      comparable movements elsewhere. As a social-intellectual phenomenon, Anglo
      American eugenics considered the Japanese racially inferior to Western peoples;
      yet eugenic ideals and policies achieved a remarkable popularity in Japan. Most
      of mainstream Japanese genetics was derived from orthodox Mendelian roots in
      Germany and (to a lesser degree) the United States. But French-style Lamarckian
      notions of the inheritability of acquired characters held surprising popularity
      among enthusiasts of eugenics. Japanese eugenicists could condemn the actions of
      foreign eugenicists like Charles Davenport in the United States for their efforts
      to forbid Japanese immigration in the 1920s, yet appeal to these same eugenicists
      as a source of legitimacy in Japan. These paradoxes can partly be explained
      against a background of relative isolation in a period of profound social change.
      Few Japanese eugenicists had close personal contact with foreign eugenicists, and
      most of their knowledge was acquired through reading rather than direct exposure.
      The eugenic ideal of ethnic purity was attractive to a society long accustomed to
      monoracial self-imagery. The need to defend national independence in an era of
      high imperialism seemed to require the most up-to-date policies and ideas. And
      Japan's own acquisition of an overseas empire seemed to demand a population
      management philosophy ostensibly based on scientific principles. These and other
      forces supported the implementation of eugenic policies and prescriptions among
      the Japanese people in the first half of the twentieth century.

PMID- 15168678
TI  - Genetic engineering in contemporary Islamic thought.
AB  - Muslims share with others both the interest in and the concern about genetic
      engineering. Naturally their reactions and views stem from general Islamic dogma
      and from Islamic medical ethics, but they are not unaware of Western scientific
      data. Particularly relevant is the Islamic religious prohibition against
      "changing what Allah has created." Muslim muftis try to offer practical solutions
      for individuals. Islamic law is concerned about maintaining pure lineage.
      Consanguineous matings are very common, but induced abortions are usually ruled
      out. Cloning has reawakened among Muslims an old debate over the positive as well
      as hazardous aspects of genetic engineering.

PMID- 15168679
TI  - Human genome research in China.
AB  - Significant progress in human genome research has been made in China since 1994.
      This review aims to give a brief and incomplete introduction to the major
      research institutions and their achievements in human genome sequencing and
      functional genomics in medicine, with emphasis on the "1% Sequencing Project",
      the generation of single nucleotide polymorphism and haplotype maps of the human
      genome, disease gene identification, and the molecular characterization of
      leukemia and other diseases. Chinese efforts towards the sequencing of pathogenic
      microbial genomes and of the rice (Oryza sativa ssp. Indica) genome are also
      described.

PMID- 15168683
TI  - [The specialty of psychosomatic medicine and its share in the evolution of
      ambulatory care].

PMID- 15168680
TI  - The Ro 60 kDa autoantigen: insights into cellular function and role in
      autoimmunity.
AB  - An RNA-binding protein, the Ro 60 kDa autoantigen, is a major target of the
      immune response in patients suffering from two systemic rheumatic diseases,
      systemic lupus erythematosus and Sjogren's syndrome. In lupus patients, anti-Ro
      antibodies are associated with photosensitive skin lesions and with neonatal
      lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children
      with photosensitive skin lesions and a cardiac conduction defect, third degree
      heart block. In vertebrate cells, the Ro protein binds small RNAs of unknown
      function known as Y RNAs. Although the cellular function of Ro has long been
      mysterious, recent studies have implicated Ro in two distinct processes: small
      RNA quality control and the enhancement of cell survival following exposure to
      ultraviolet irradiation. Most interestingly, mice lacking the Ro protein develop
      an autoimmune syndrome that shares some features with systemic lupus
      erythematosus in patients, suggesting that the normal function of Ro may be
      important for the prevention of this autoimmune disease. In this review, we
      summarize recent progress towards understanding the role of the Ro 60 kDa protein
      and discuss whether the cellular function of Ro could be related to certain
      manifestations of lupus in patients.

PMID- 15168681
TI  - Effective induction of immune tolerance by portal venous infusion with IL-10 gene
      modified immature dendritic cells leading to prolongation of allograft survival.
AB  - Dendritic cells (DC) not only initiate T cell responses, but are also involved in
      the induction of tolerance. The functional properties of DC are strictly
      dependent on their state of maturation. It has been shown that immature DC can
      induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is
      an important immunosuppressive cytokine which inhibits maturation and function of
      DC. In order to improve the tolerogenicity of DC, we and others showed that
      adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and
      IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12
      secretion and the T cell stimulatory capacity of DC. The primary aim of this
      study is to examine the in vivo effects of this approach on allograft survival in
      a murine cardiac allograft transplantation model. To our surprise,we observed
      that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via
      the tail vein could not prolong allograft survival in the recipients, but
      shortened their survival. More interestingly, portal venous infusion of DC-IL-10
      markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion
      through different routes may be due to the different immune responses to
      alloantigens in recipients that received DC-IL-10 via either the portal or the
      tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell
      stimulating activity of liver DC and enhanced incidence of donor DC in the
      recipients may contribute to the more efficient prolongation of allograft
      survival observed after portal venous infusion of DC-IL-10. These results suggest
      that portal venous infusion may be an effective approach for immature DC to
      induce immune tolerance or hyporesponsiveness against donor antigens, and prolong
      allograft survival.

PMID- 15168684
TI  - [Need analysis for inpatient care according to SGBV Paragraph 39 for the
      specialty of psychotherapy medicine by the Lower Saxony Department of Social,
      Women, Family and Health Services].

PMID- 15168685
TI  - Current awareness in NMR in biomedicine.

PMID- 15168687
TI  - 'A milestone' in treatment for renal cell cancer.

PMID- 15168688
TI  - ERC--new cornerstone of European research or more of the same?

PMID- 15168689
TI  - Thiomersal in vaccines: a regulatory perspective WHO Consultation, Geneva, 15-16
      April 2002.

PMID- 15168686
TI  - The clinical trials directive: what next?

PMID- 15168690
TI  - Biological significance of DNA adducts: summary of discussion of expert panel.

PMID- 15168691
TI  - An interview with Mary Lyon [interviewed by Nick Campbell].

PMID- 15168696
TI  - Genomic variants in exons and introns: identifying the splicing spoilers.

PMID- 15168695
TI  - The inevitability of genetic enhancement technologies.
AB  - We outline a number of ethical objections to genetic technologies aimed at
      enhancing human capacities and traits. We then argue that, despite the
      persuasiveness of some of these objections, they are insufficient to stop the
      development and use of genetic enhancement technologies. We contend that the
      inevitability of the technologies results from a particular guiding worldview of
      humans as masters of the human evolutionary future, and conclude that recognising
      this worldview points to new directions for ethical thinking about genetic
      enhancement technologies.

PMID- 15168698
TI  - Evidence-based medicine and women: do the principles and practice of EBM further
      women's health?
AB  - Clinicians and policy makers the world over are embracing evidence-based medicine
      (EBM). The promise of EBM is to use summaries of research evidence to determine
      which healthcare interventions are effective and which are not, so that patients
      may benefit from effective interventions and be protected from useless or harmful
      ones. EBM provides an ostensibly rational objective means of deciding whether or
      not an intervention should be provided on the basis of its effectiveness, in
      theory leading to fair and effective healthcare for all. In this paper I closely
      examine these claims from the perspective of healthcare for women, using relevant
      examples. I argue that the current processes of evidence-based medicine contain a
      number of biases against women. These biases occur in the production of research
      that informs evidence-based medicine, in the methods used to analyse and
      synthesise the evidence, and in the application of EBM through the use of
      guidelines. Finally, the biomedical model of health that underpins most of the
      medical research used by EBM ignores the social and political context which
      contributes so much to the ill-health of women.

PMID- 15168697
TI  - Coding and consent: moral challenges of the database project in Iceland.
AB  - A major moral problem in relation to the deCODE genetics database project in
      Iceland is that the heavy emphasis placed on technical security of healthcare
      information has precluded discussion about the issue of consent for participation
      in the database. On the other hand, critics who have emphasised the issue of
      consent have most often demanded that informed consent for participation in
      research be obtained. While I think that individual consent is of major
      significance, I argue that this demand for informed consent is neither suitable
      nor desirable in this case. I distinguish between three aspects of the database
      and show that different types of consent are appropriate for each. In particular,
      I describe the idea of a written authorisation based on general information about
      the database as an alternative to informed consent and presumed consent in
      database research.

PMID- 15168699
TI  - On our obligation to select the best children: a reply to Savulescu.
AB  - The purpose of this paper is to examine critically Julian Savulescu's claim that
      people should select, of the possible children they could have, the one who is
      expected to have the best life, or at least as good a life as the others, based
      on the relevant, available genetic information, including information about non
      disease genes. I argue here that in defending this moral obligation, Savulescu
      has neglected several important issues such as access to selection technologies,
      disproportionate burdens on women, difficulties in determining what is best,
      problems with aggregate effects of individual choices, and questions about social
      justice. Taking these matters into account would call such a moral requirement
      into serious question.

PMID- 15168700
TI  - Eugenic values.
AB  - Eugenics is generally regarded as evil; but what was its sin? Racism, class bias,
      and violation of reproductive freedom, which tainted objectionable eugenic
      interventions, are not part of the core notion of eugenics. A number of
      candidates have been suggested as the wrong inherent in eugenics, ranging from
      statism to the impossibility of consensus on the ideal human being. It is most
      plausible to view eugenics as sharing moral dilemmas with much of public health,
      and the critical issues as those of distributive justice.

PMID- 15168701
TI  - Give Kids a Smile Day.

PMID- 15168703
TI  - Abstracts of the Autumn Meeting of the Neonatal Society. 20 November 2003,
      London, United Kingdom.

PMID- 15168702
TI  - The Gold Medal for Distinguished Service--TDA's highest honor.

PMID- 15168707
TI  - [Advances in the study of Chinese herbal drug dripping pills].

PMID- 15168710
TI  - You are what you serve: are school districts liable for serving unhealthy food
      and beverages to students?

PMID- 15168711
TI  - Planned Parenthood is not a bank: closing the clinic doors to the Fourth
      Amendment third party doctrine.

PMID- 15168712
TI  - Prescription drug safety.

PMID- 15168713
TI  - Does health insurance affect health care utilization and health?

PMID- 15168715
TI  - The effect of air pollution on infant health.

PMID- 15168714
TI  - Professor Emly Glyn Vaughan Evans 4th October 1941-4th August 2003.

PMID- 15168716
TI  - [Current status of vestibular rehabilitation].

PMID- 15168717
TI  - Cellular nucleoside pharmacokinetics and pharmacology: a potentially important
      determinant of antiretroviral efficacy.
AB  - Among the potential reasons for treatment failure in patients receiving therapy
      for HIV-1 infection, one that has received only limited attention is
      intracellular interactions between nucleosides that may reduce their metabolism
      (phosphorylation) to active forms necessary for antiretroviral activity. Results
      reviewed in this paper indicate that there is considerable potential for
      interaction among nucleosides used to suppress viral replication in patients with
      HIV-1 infection. Zidovudine (ZDV) and zalcitabine (ddC) have both been shown to
      inhibit their own metabolism. ZDV also inhibits the phosphorylation of stavudine
      (d4T) and lamivudine (3TC) and increases that of didanosine (ddI). d4T has been
      shown to slightly decrease the phosphorylation of ZDV. ddC decreases the
      formation of triphosphates of both d4T and 3TC, and 3TC decreases the
      phosphorylation of ddC. ddI has no significant effects on the intracellular
      metabolism of any of the nucleoside analogues currently used to treat patients
      with HIV-1 disease. Thus, the pharmacokinetics of antiretroviral agents and
      intracellular phosphorylation/activation of nucleosides may be important
      determinants of the virologic and clinical effectiveness of therapy. They must be
      considered along with characteristics of the virus, such as phenotypic and
      genotypic resistance, and those of the patient, including motivation to adhere to
      therapy, in individualizing antiretroviral treatment regimens for individuals
      with HIV-1 disease.

PMID- 15168718
TI  - Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in
      combination with either didanosine or lamivudine.
AB  - This paper reviews the results of three trials, HIV NAT002, AI455-053, and AIDS
      Clinical Trials Group (ACTG) 306, all of which evaluated the effectiveness of
      stavudine (d4T)-containing two-nucleoside combinations in antiretroviral-naive
      patients with human immunodeficiency virus type 1 (HIV-1) infection. The latter
      two studies directly compared d4T plus didanosine (ddI) or lamivudine (3TC)
      versus zidovudine (ZDV) plus each of these two nucleosides. The combined results
      of the three trials support the conclusion that d4T can be used effectively in
      combination with either ddI or 3TC to reduce viral loads and increase CD4 cell
      counts in patients with HIV-1 infection. The results of AI455-053 and ACTG 306
      show further that combination of d4T with either ddI or 3TC is at least as
      effective as the use of ZDV with these nucleosides.

PMID- 15168719
TI  - Combination therapy for patients with HIV-1 infection: the use of dual nucleoside
      analogues with protease inhibitors and other agents.
AB  - This report reviews the design and preliminary results of ongoing and new studies
      that are evaluating novel antiretroviral drug combinations for the treatment of
      patients with HIV-1 infection. The studies reviewed in this report are: (1)
      Selection of Thymidine Analogue Regimen Therapy (START) I and II which compare
      three-drug combinations of stavudine (d4T), lamivudine (3TC), and indinavir, or
      d4T, didanosine (ddI), and indinavir versus zidovudine (ZDV), 3TC, and indinavir;
      (2) ATLANTIC, a study that compares d4T and didanosine (ddI) in combination with
      a third agent, either 3TC, nevirapine, or indinavir; and (3) the OZCOMBO studies:
      OZCOMBO 1, which compares two-drug combinations of d4T and 3TC, d4T and ddI, and
      ZDV and 3TC, all in combination with indinavir, and OZCOMBO 2, which compares two
      drug combinations of d4T and ddI, ZDV and ddI, and ZDV and 3TC, all in
      combination with nevirapine. Preliminary results from these studies suggest that
      novel dual-nucleoside analogue reverse transcriptase inhibitor pairs, d4T and
      3TC, d4T and ddI, and ZDV and ddI, as part of three-drug combinations, achieve
      antiretroviral effects comparable to ZDV- and 3TC-based three-drug combination
      regimens.

PMID- 15168720
TI  - Improving patient adherence with antiretroviral therapy: evaluation of once-daily
      administration of didanosine.
AB  - One important goal of antiretroviral therapy should be simplification of
      treatment regimens whenever possible, in order to enhance adherence and
      potentially improve treatment outcome. While the nucleoside didanosine (ddI) has
      generally been dosed twice daily in clinical trials, the long intracellular half
      life (>12 h) of its active metabolite, dideoxyadenosine triphosphate, should
      permit once-daily administration of this antiretroviral agent. The STADI trial
      evaluated this possibility by administering once-daily ddI and twice-daily
      stavudine (d4T) to antiretroviral-naive patients with human immunodeficiency
      virus type 1 (HIV-1) infection. This combination was well tolerated and at the
      end of 24 weeks of therapy, viral load was reduced by -1.48 log copies/ml and HIV
      1 RNA was below the lower limit of quantification (500 copies/ml) in 62% of
      patients. Twenty-four weeks of treatment with d4T plus once-daily ddI increased
      average CD4 cell counts by 139/ml. The effectiveness of once-daily administration
      of ddI will be evaluated further in a new multinational clinical trial, AI454
      148, in which it will be combined with d4T and the protease inhibitor,
      nelfinavir. The primary endpoint of this trial will be durable reduction of
      plasma HIV-1 RNA below 400 copies/ml. Such a change in the treatment regimen for
      this nucleoside has the potential to improve patient adherence and, thus,
      treatment outcome.

PMID- 15168721
TI  - Variation of genetic expression during development, revealed by esterase patterns
      in Aedes aegypti (Diptera, Culicidae).
AB  - Polyacrylamide gel electrophoresis was used to analyze esterase patterns during
      development of Aedes aegypti from the cities of Marilia and Sao Jose do Rio Preto
      (SJRP), Brazil. The zymograms showed a total of 23 esterase bands, 22 of which
      were in the specimens from Marilia and 19 in those from SJRP. These esterase
      bands were considered to be the product of 23 alleles distributed tentatively in
      eight genetic loci. Most of the alleles were developmentally regulated. The
      larval stage expressed the greatest number of them (19 alleles, from the eight
      loci, in Marilia; and 17 alleles, from seven loci, in SJRP). The pupal stage
      expressed 10 alleles from seven loci, in both populations, and the adult stage
      expressed 8 alleles from five and six loci in SJRP and Marilia, respectively.
      Some alleles that were active in every stage were developmentally controlled at
      the level of expression (amount of product). A single allele was constitutively
      and highly expressed, in larvae, pupae, and adults, in both populations.
      Differences in esterase synthesis among stages are probably due to regulatory
      mechanisms acting in agreement with the requirements of a variable number of
      processes in which esterases are involved. The larval stage is the most active in
      developmental processes and shows very intense intake of food and very high
      mobility. These features may demand increased esterase production at that stage.
      Comparison of the two populations examined showed (besides the existence of
      alleles that they do not share) that they exhibit differences in the control of
      expression of other alleles. Such findings may reflect genetic differences
      between founders in each population, but the possibility of involvement of the
      intensive use of insecticides in SJRP is also discussed.

PMID- 15168722
TI  - Amino acid disorders in mental retardation: a two-decade study from Andhra
      Pradesh.
AB  - A screening program was carried out for amino acid disorders in children with
      mental handicaps from the state of Andhra Pradesh (India) during the last two
      decades. Forty-one (0.9%) cases were detected with amino acid disorders among
      4500 children surveyed. We reported amino acid disorders of rare occurrence such
      as dicarboxylic aminoaciduria, hydroxykynureninuria, persistent hypertyrosinemia,
      hydroxyprolinemia, hypervalinemia, etc. A new metabolic defect threoninemia was
      also detected. We have observed a preponderance of males with amino acid
      disorders. Parental consanguinity was present in 54% of cases with amino acid
      disorders.

PMID- 15168723
TI  - Analysis of the genetic structure of endangered bovine breeds from the Western
      Pyrenees using DNA microsatellite markers.
AB  - In the Western Pyrenees, three out of four native cattle breeds are in grave
      danger of extinction. Genetic variation of all four breeds was assessed by
      analyzing 478 animals using 11 microsatellite markers. A moderate/high within
      breed variability was found, a favorable factor to consider when planning
      conservation and improvement programs. Interestingly, the only selected
      commercial breed, the Pirenaica, showed depressed heterozygosity levels and a low
      average number of alleles, perhaps explainable by intensive human selection
      exacerbated by a bottleneck effect. The Pirenaica also exhibited pronounced
      genetic differences and was the largest contributor of diversity among the breeds
      from the Western Pyrenees. Among endangered cattle breeds from this region, our
      results highlight the singularity of the Betizu. Geographic isolation among herds
      may be responsible for the large F(IS) value found in the Betizu breed. Lastly,
      our study suggests that the use of highly selected breeds may be one of the
      causes of distortion in phylogenetic analyses.

PMID- 15168724
TI  - High genetic variability of esterase loci in natural populations of Parus major,
      P. caeruleus, and P. ater.
AB  - In Parus major, P. caeruleus, and P. ater the genetic variation of 16 isozyme
      loci was determined. The focus was on esterases that show high phenotypic
      variation in natural populations of these species. The degree of heterozygosity
      of the "non-esterase" loci was 0.029 +/- 0.008 (P. major); 0.023 +/- 0.012 (P.
      caeruleus), and 0.034 +/- 0.034 (P. ater). Including the esterase loci with up to
      six alleles per locus the overall degree of heterozygosity increased to 0.130 +/-
      0.056 (P. major); 0.143 +/- 0.067 (P. caeruleus), and 0.194 +/- 0.090 (P. ater).
      We explain the high level of variability of esterases by gene amplification and
      subsequent selection for high allelic heterogeneity. Substrate specificity of
      loci is assumed to allow for multiple resistance against various toxic
      components. Large allelic valiation of esterases, therefore, increases the
      fitness of Parus species and allows for utilizing new food resources.

PMID- 15168725
TI  - High-speed detection of the G894T polymorphism in exon 7 of the eNOS gene by real
      time fluorescence PCR with the Light-Cycler.
AB  - In endothelial cells nitric oxide (NO) is synthesized by endothelial-nitric oxide
      synthase (e-NOS), constitutively expressed and encoded by a 26-exon gene, located
      on chromosome 7q35-36. The prevalence of the T rare variant of the G894T
      polymorphism in exon 7 of the e-NOS gene (Glu-->Asp amino acid substitution) has
      been reported to be significantly higher in patients with coronary spasm and
      coronary artery disease. To date G894T polymorphism detection is performed by PCR
      RFLP assay. In order to establish a high-speed genotyping method, we have taken
      advantage of the Light Cycler instrument, a thermal cycler that combines rapid
      cycle DNA amplification with a real-time fluorescence monitoring. This technology
      is based on hybridization of the adjacent fluorescently labeled probes with PCR
      products. This methodology is considered more accurate and less time-consuming
      than conventional PCR-RFLP assay. To validate this technique we genotyped 270
      healthy subjects. The results were consistent with those obtained from PCR-RFLP
      assay.

PMID- 15168726
TI  - Cloning and characterization of a novel human TGF-beta activated kinase-like
      gene.
AB  - TGF-beta activated kinase (TAK1) plays a critical role in the TGF-beta signaling
      transduction pathway. By screening a human 18-week fetal brain library, we
      isolated a novel human TAK1-like (TAKL) gene. The gene encoded a putative protein
      of 242 amino acids, which shared a homology with human, mouse, and Xenopus TAK1.
      The TAKL gene was located in chromosome 21q21. Northern blot analysis revealed
      that the TAKL mRNA was expressed predominantly in peripheral blood leukocytes and
      ubiquitously in human adult and fetal tissues. TAKL was also expressed strongly
      in breast carcinoma GI-101, colon adenocarcinoma GI-112, and prostatic
      adenocarcinoma PC3.

PMID- 15168727
TI  - Cathepsin D expression levels in nongynecological solid tumors: clinical and
      therapeutic implications.
AB  - Cathepsin D is a lysosomal acid proteinase which is involved in the malignant
      progression of breast cancer and other gynecological tumors. Clinical
      investigations have shown that in breast cancer patients cathepsin D
      overexpression was significantly correlated with a shorter free-time disease and
      overall survival, whereas in patients with ovarian or endometrial cancer this
      phenomenon was associated with tumor aggressiveness and a degree of
      chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum
      and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate
      the role and the prognostic value of cathepsin D also in other solid neoplasms.
      However, conflicting results have been generated from these studies. The
      discrepancies in these results may, in part, be explained with the different
      methodological approaches used in order to determine the levels of expression of
      the enzyme in tumor tissues and body fluids. Further investigations using well
      standardized techniques may better define the clinical significance of cathepsin
      D expression in solid tumors. Nevertheless, evidence emerging from these studied
      indicates that this proteinase seems to facilitate early phases of tumor
      progression such as cell proliferation and local dissemination. These findings
      support the concept that cathepsin D may be a useful marker for identifying
      patients with highly malignant tumor phenotypes who may need more aggressive
      clinical treatment; this enzyme may also be considered as a potential target for
      a novel therapeutic approach in the treatment of solid neoplasms.

PMID- 15168728
TI  - Vascular endothelial growth factor expression promotes the growth of breast
      cancer brain metastases in nude mice.
AB  - Patients with breast cancer brain metastases cannot be cured and have a poor
      prognosis, with a median survival time of six months after diagnosis, despite
      developments in diagnostic and therapeutic modalities. In large part the progress
      in understanding the biology of breast cancer brain metastasis has been limited
      by the lack of suitable cell lines and experimental models. The objective of this
      study was to develop a reliable experimental model to study the pathogenesis of
      breast cancer brain metastases, using intra-internal carotid artery injection of
      breast cancer cells into nude mice. Brain metastasis-selected variant cells were
      recovered after three cycles of injection into the internal carotid artery of
      nude mice and harvest of brain metastases, resulting in variants termed MDA-231
      BR1, -BR2 and -BR3. The metastasis-selected cells had increased potential for
      experimental brain metastasis and mice injected with these cells had
      significantly shorter mean survival than mice injected with the original cell
      line. Brain metastatic lesions of the selected variants contained significantly
      more CD31-positive blood vessels than metastases of the non-selected cell line.
      The variants selected from brain metastases released significantly more VEGF-A
      and IL-8 into culture supernatants than the original cell line, and more VEGF-A
      RNA when cultured in normoxic conditions. Mice injected with MDA-231 BR3 into the
      carotid artery were treated with the VEGF-receptor tyrosine kinase inhibitor
      PTK787/Z 222584. Oral administration of the inhibitor resulted in a significant
      decrease in brain tumor burden, reduced CD31-positive vessels in the brain
      lesions and incidence of PCNA positive tumor cells, and increased apoptosis in
      the tumor, as measured by TUNEL labeling. We conclude that elevated VEGF
      expression contributes to the ability of breast cancer cells to form brain
      metastases. Targeting endothelial cells with a VEGF-receptor specific tyrosine
      kinase inhibitor reduced angiogenesis and restricted the growth of the brain
      metastases.

PMID- 15168729
TI  - A small molecule antagonist of the alpha(v)beta3 integrin suppresses MDA-MB-435
      skeletal metastasis.
AB  - INTRODUCTION: Breast cancer is one of the most common malignancies affecting
      women in the United States and Europe. Approximately three out of every four
      women with breast cancer develop metastases in bone which, in turn, diminishes
      quality of life. The alpha(v)beta3 integrin has previously been implicated in
      multiple aspects of tumor progression, metastasis and osteoclast bone resorption.
      Therefore, we hypothesized that the alpha(v)beta3-selective inhibitor, S247,
      would decrease the development of osteolytic breast cancer metastases. MATERIALS
      AND METHODS: Cells were treated in vitro with S247 and assessed for viability and
      adhesion to matrix components. Athymic mice received intracardiac (left
      ventricle) injections of human MDA-MB-435 breast carcinoma cells expressing
      enhanced green-fluorescent protein. Mice were treated with vehicle (saline) or
      S247 (1, 10, or 100 mg/kg/d) using osmotic pumps beginning either one week before
      or one week after tumor cell inoculation. Bones were removed and examined by
      fluorescence microscopy and histology. The location and size of metastases were
      recorded. RESULTS AND CONCLUSIONS: IC50 for S247 adhesion to alpha(v)beta3 or
      alpha(IIB)beta3a substrates was 0.2 nM vs. 244 nM, respectively. Likewise, S247
      was not toxic at doses up to 1000 microM. However, osteoclast cultures treated
      with S247 exhibited marked morphological changes and impaired formation of the
      actin sealing zone. When S247 was administered prior to tumor cells, there was a
      significant, dose-dependent reduction (25-50% of vehicle-only-treated mice; P =
      0.002) in osseous metastasis. Mice receiving S247 after tumor cell inoculation
      also developed fewer bone metastases, but the difference was not statistically
      significant. These data suggest that, in the MDA-MB-435 model, the alpha(v)beta3
      integrin plays an important role in early events (e.g., arrest of tumor cells) in
      bone metastasis. Furthermore, the data suggest that alpha(v)beta3 inhibitors may
      be useful in the treatment and/or prevention of breast cancer metastases in bone.

PMID- 15168732
TI  - Identification of metastasis-associated proteins through protein analysis of
      metastatic MDA-MB-435 and metastasis-suppressed BRMS1 transfected-MDA-MB-435
      cells.
AB  - BRMS1 (breast cancer metastasis suppressor 1) was recently identified as a novel
      breast cancer metastasis suppressor gene. To further characterize BRMS1-mediated
      metastasis suppression, we applied two-dimensional proteomic and mass
      spectrometry (LC-tandem MS and MALDI-TOF) analysis to identify proteins
      differentially expressed between highly metastatic MDA-MB-435 cells and
      metastasis-suppressed BRMS1-transfected MDA-MB-435 cells. Quadruplicate
      independent 2D gels were run and analyzed under identical conditions. Following
      in-gel trypsin digestion of seven differentially expressed proteins, amino acid
      sequence and mass profiles of the peptides were generated. Proteins were
      identified from the NCBI non-redundant database using the search program
      TurboSequest. Differential expression was confirmed for five proteins, including
      annexin I and alpha B-crystallin, by Northern blot analysis and immunostaining.
      Furthermore, we showed that both proteins were expressed in vivo in lungs
      containing metastasized MDA-MB-435 cells but not expressed in normal lung tissue
      of athymic mice. Our results suggest that annexin I and alpha B-crystallin are
      important cellular proteins that are down regulated through BRMS1 mediated
      metastasis suppression.

PMID- 15168730
TI  - Anti-metastatic properties of RGD-peptidomimetic agents S137 and S247.
AB  - Integrins expressed on endothelial cells modulate cell migration and survival
      during angiogenesis. Integrins expressed on carcinoma cells potentiate metastasis
      by facilitating invasion and movement across blood vessels. We describe the
      activities of two synthetic low-molecular-weight peptidomimetics of the ligand
      amino acid sequence arg-gly-asp (RGD) in integrin-based functional assays in
      vitro. We also evaluate efficacy and potential mechanisms of action in models of
      both spontaneous and experimental metastasis. Broad-spectrum potency against the
      family of alpha v subunit-containing integrins was observed, with significantly
      less potency against alpha5beta1 and alpha(IIb)beta3. Both endothelial and tumor
      cell migration mediated by alpha(v)beta3 was inhibited, whereas proliferation of
      endothelial cells but not tumor cells was diminished. Continuous infusion of
      compound by minipumps or oral administration twice daily significantly reduced
      metastatic tumor burden in the lungs of mice despite no reduction in growth of
      435/HAL primary tumors, and only a slight reduction in tumor cells detected in
      circulating blood. Delaying treatment in this model until after extensive
      dissemination of tumor cells to the lungs had occurred, and after primary tumor
      resection, still produced significant efficacy. Conversely, administration of the
      agent for only the first 18 h after tumor-cell inoculation into the tail vein
      also resulted in decreased metastases observed after several weeks. These data
      suggest these compounds or their relatives have potential to interfere with both
      early and late steps of metastasis involving tumor and endothelial cell
      functions. Furthermore, the metastatic process can be effectively inhibited
      independently of primary tumor growth using integrin antagonists.

PMID- 15168731
TI  - Antigenic differences between metastatic cells in bone marrow and primary tumours
      and the anti-MUC1 humoral immune response induced in breast cancer patients.
AB  - The dissemination of a malignant neoplasia is a complex process, which requires a
      set of molecules that remains unknown. It has been suggested that mucins and
      their carbohydrate-associated antigens may be implicated in tumour spreading
      which may be also influenced by an anti-MUC1 immune response. In this pilot
      study, we report the pattern of carbohydrate and peptidic MUC1-associated
      epitopes on carcinoma cells isolated from bone marrow (BM), taking into account
      primary tumour histopathologic features. We also bring information about the anti
      MUC1 humoral response in these patients. Seventeen patients with invasive breast
      carcinoma were included. A sample of the primary tumour, a serum sample and a BM
      aspirate were obtained from each patient. Clinical features studied were tumour
      size, number of metastatic nodes, histological type and disease stage. Standard
      immunohistochemistry was performed with antigenic retrieval using different
      monoclonal antibodies (MAbs): anti carbohydrate antigens: Lewis x (KM380), sLewis
      x (KM93), Lewis y (C14) and Tn, anti-MUC1 peptide core MAbs: C595, HMFG2 and SM3,
      anti-cytokeratins, anti-protoncogenes ErbB2 and ErbB3 (IgG) MAbs and also anti
      CD34 and anti-CD45 MAbs. ELISA techniques were employed to study circulating MUC1
      as well as free and complexed anti-MUC1 antibodies. Immunohistochemical results
      showed that carbohydrate antigenic expression increases in BM neoplastic cells
      compared to the original tumours. However, we were not able to demonstrate that a
      humoral immune response to MUC1 has been induced in these patients. Finally, the
      employed procedures allow the selective immortalisation of micrometastatic
      carcinoma cells since short-term cell lines were established.

PMID- 15168733
TI  - A soybean Kunitz trypsin inhibitor suppresses ovarian cancer cell invasion by
      blocking urokinase upregulation.
AB  - We have previously reported in a series of papers that a Kunitz-type protease
      inhibitor, bikunin, suppresses up-regulation of urokinase-type plasminogen
      activator (uPA) and its specific receptor (uPAR) expression, phosphorylation of
      ERK1/2 and cancer cell invasion in vitro and peritoneal disseminated metastasis
      in vivo. In the present study, we investigated the effects of soy bean trypsin
      inhibitor (SBTI) on the net enzymatic activity of secreted, extracellular uPA,
      signal transduction involved in the expression of uPA and invasion in HRA human
      ovarian cancer cells. SBTI contains a Kunitz trypsin inhibitor (KTI) and a Bowman
      Birk inhibitor (BBI). Here, we show 1) that KTI and BBI were purified separately
      from soybeans; 2) that neither KTI nor BBI effectively inhibits enzymatic
      activity of uPA; 3) that uPA upregulation observed in HRA cells was inhibited by
      preincubation of the cells with KTI with an IC50 of approximately 2 microM,
      whereas BBI failed to repress uPA upregulation, as measured by enzyme-linked
      immunosorbent assay; 4) that cell invasiveness was inhibited by treatment of the
      cells with KTI with an IC50 of approximately 3 microM, whereas BBI failed to
      suppress cell invasion, as measured by an in vitro invasion assay; 5) KTI
      suppresses HRA cell invasion by blocking uPA up-regulation which may be mediated
      by a binding protein(s) other than a bikunin binding protein and/or its receptor;
      and 6) that transforming growth factor-beta 1 (TGF-beta1)-mediated activation of
      ERK1/2 was significantly reduced by preincubation of the cells with KTI. In
      conclusion, KTI, but not BBI, could inhibit cell invasiveness at least through
      suppression of uPA signaling cascade, although the mechanisms of KTI may be
      different from those of bikunin.

PMID- 15168736
TI  - HIV antiretroviral drug resistance in Africa.
AB  - Highly active antiretroviral therapy (HAART) has dramatically reduced mortality
      and morbidity in HIV-infected persons in developed countries. Although the use of
      HAART remains limited in Africa, there are global efforts to make available these
      drugs to several million HIV-infected persons on the continent. In this review we
      examine the impact of HIV genetic diversity on the occurrence of drug-resistance
      mutations among non-B subtypes, and discuss the implication of resistant strains
      in programs aimed at implementing antiretroviral treatment (ART) in Africa, with
      respect to factors that may favor the occurrence of treatment-acquired drug
      resistant viruses, ways to monitor for drug resistance, and strategies to limit
      its occurrence. We assert that antiretroviral drug resistance is an inevitable
      consequence when providing long-term treatment, and should not be seen as a
      limitation of providing antiretrovirals to patients in resource-poor settings,
      but rather a necessary challenge to be incorporated into the rational design of
      programs that provide ART in Africa.

PMID- 15168735
TI  - Angiogenic and antiangiogenic balance regulates concomitant antitumoral
      resistance.
AB  - Concomitant antitumoral resistance (CAR), the phenomenon by which the growth of
      distant secondary tumor implants or metastases in some tumor-bearing hosts is
      inhibited by the presence of a primary tumor, has been previously ascribed to an
      antiangiogenic process. Here, we investigated vascular endothelial growth factor
      (VEGF) and endostatin serum levels in nude or BALB/c mice bearing human lung
      tumors (Calu-6 and H460) or murine mammary tumors (M3MC, M-234p and M-234m),
      respectively. In these experimental models we previously found an association
      between in vivo generation of CAR and in vitro conversion of plasminogen into
      angiostatin. Serum endostatin level in CAR+ Calu-6-bearing mice was significantly
      higher than in CAR- H460 counterpart. Sera from mammary tumor-bearing mice showed
      similar levels of endostatin, regardless of their ability to induce CAR.
      Conversely, serum VEGF levels in mice bearing CAR+ tumors were lower than those
      found in CAR- tumor-bearing hosts. Immunostaining with an anti-CD31 antibody
      revealed that secondary tumors subjected to CAR were significantly less
      vascularized than primary tumors, while this difference was not observed in CAR-
      tumors. In vitro studies showed an inhibitory effect of sera from CAR-inducing
      tumors on endothelial cell proliferation as compared to normal sera, whereas sera
      from non-CAR-inducing tumors did not alter endothelial proliferation and, in some
      instances, even caused stimulation of endothelial proliferation. These data
      suggest that the antiangiogenic mechanism operating in concomitant antitumoral
      resistance is the result of an increase in the ratio of
      antiangiogenic/proangiogenic regulators. The levels of the factors involved in
      this phenomenon can vary in the different tumor models, but the trend favoring
      the inhibition of angiogenesis is always conserved.

PMID- 15168734
TI  - Oncostatin M stimulates the detachment of a reservoir of invasive mammary
      carcinoma cells: role of cyclooxygenase-2.
AB  - Previously, oncostatin M (OSM) has been shown to inhibit the proliferation of
      breast cancer cells in vitro. Circumstantial evidence, however, suggests that OSM
      could be involved in the development of a metastatic phenotype in vivo. We
      examined the effects of OSM on the proliferation and metastatic potential of the
      murine mammary carcinoma cell lines M6 (adenocarcinoma) and M6c (metastatic
      adenocarcinoma). OSM inhibits the proliferation of both cell lines by 43%, but
      also causes a loss of cell-cell and cell-substratum adhesion that culminates in
      cell detachment from monolayer culture. OSM treatment results in a 258% and 550%
      increase in the detachment of M6 and M6c, respectively, in 32 hours. This effect
      was abrogated by the selective Cox-2 inhibitor NS-398, and by the anti
      inflammatory glucocorticoid dexamethasone. Exogenous prostaglandin E2 (PGE2)
      partially reverses NS-398's inhibition of OSM-induced cell detachment, indicating
      Cox-2 involvement. In addition, OSM induces the expression of Cox-2 mRNA, and of
      the 74 kDa form of Cox-2 protein. M6 and M6c cells detached by OSM are viable and
      will re-adhere and proliferate in the absence of OSM. OSM-detached cells (M6DET
      and M6cDET) were collected and maintained in culture and their invasiveness was
      assessed in vitro. Importantly, M6DET and M6cDET are both significantly more
      invasive that their respective parental cells. These data suggest that OSM could
      contribute to the development of a metastatic phenotype in vivo, which would
      render OSM unsuitable as a cancer therapy and suggest that OSM itself is a
      potential therapeutic target.

PMID- 15168737
TI  - Integration site selection by retroviruses.
AB  - Integration into the host-cell genome is a critical step in the retrovirus life
      cycle. In particular, the choice of the integration site is crucial for
      retroviral replication, since integration at a site incompatible for high-level
      transcription may impair production of the progeny virus. Integration is not
      sequence specific, thus all chromosomal sites could potentially host integration
      events. However, this is not what is observed in vivo, where integrated viruses
      are preferentially detected in chromatin regions characterized by an open
      structure, a hallmark of actively transcribed genes. Target site selection might
      be influenced by several factors, including the function of cellular proteins
      that interact with integrase, the viral protein that catalyzes the integration
      reaction. Interestingly, a common functional feature that unifies these cellular
      co-factors is that, to a different extent, they are all involved in the
      regulation of chromatin structure or transcription. Inappropriate retroviral
      integration might lead to insertional mutagenesis and cellular transformation, as
      recently observed in a gene therapy clinical trial exploiting retroviral vectors
      for gene transfer into hematopoietic progenitors. Thus, the deeper understanding
      of the molecular mechanisms regulating integration site selection is also
      essential for the design of safer and more effective gene transfer vectors.

PMID- 15168738
TI  - K65R, TAMs and tenofovir.
AB  - The management of drug resistance has become part of the management of HIV
      disease in the treated individual. As two or more nucleoside reverse
      transcriptase inhibitors (NRTIs) are generally part of each antiretroviral
      regimen, there is a need to fully understand resistance and cross-resistance
      within this class of drugs. Broad cross-resistance to NRTIs caused by the group
      of HIV RT mutations associated with zidovudine and stavudine therapy (thymidine
      analogue mutations or TAMs) has been well established. The response to tenofovir
      disoproxil fumarate (TDF) therapy is also limited by certain patterns of TAMs (>
      or = 3 TAMs with M41L or L210W). The K65R mutation can result from tenofovir DF,
      abacavir, stavudine, zalcitabine or didanosine therapy. From in vitro phenotypic
      analysis, the K65R mutation shows no cross-resistance to zidovudine, but low
      level resistance to tenofovir and the other NRTIs. Based on clinical cut-offs
      established for the individual NRTIs, the phenotypic results with K65R suggest
      full-to-partial drug activity for multiple NRTIs, including tenofovir, against
      the K65R mutant. Similar to the M184V mutation, the K65R mutation is also
      associated with reduced in vitro viral replication capacity, hallmarks of which
      can be demonstrated at the enzymatic level. From cross-sectional genotypic
      analyses, the K65R mutation and TAMs appear to represent separate patterns of
      NRTI resistance. Among treatment-naive patients who developed the K65R mutation
      in clinical trials, successful second line regimens were established. Thus, the
      K65R mutation appears manageable for the sequencing of treatment regimens in the
      case of its development.

PMID- 15168739
TI  - New insights into the role of Vif in HIV-1 replication.
AB  - HIV-1 and most of the other lentiviruses encode Vif (virion infectivity factor),
      an accessory protein that the virus requires to replicate in primary CD4+ T-cells
      and monocytes. The host cell factor with which Vif interacts was recently
      identified as APOBEC3G, a cytidine deaminase related to the RNA-editing enzymes.
      Identification of this key host protein has allowed for dramatic leaps in our
      understanding of how Vif functions. Vif prevents the encapsidation of APOBEC3G
      into HIV-1 virions during virus assembly. If not for Vif, the encapsidated
      APOBEC3G would damage the virus reverse transcripts, causing their degradation
      and closing the open reading frames of its genes.

PMID- 15168740
TI  - What can natural infection of African monkeys with simian immunodeficiency virus
      tell us about the pathogenesis of AIDS?
AB  - The simian immunodeficiency viruses are a diverse group of viruses that naturally
      infect a wide range of African primates, including chimpanzees, African green
      monkeys (AGM) and sooty mangabey monkeys (SM). Although natural infection is
      widespread in feral populations of AGMs and SMs, this infection does not result
      in immunodeficiency. However, experimental inoculation of Asian macaque species
      results in an immunodeficiency syndrome that is remarkably similar in
      pathogenesis to human AIDS. Thus, SIVsm infection of macaques results in AIDS,
      and similarly experimental inoculation of pigtailed macaques with at least one
      SIVagm isolate, SIVIhoest or SIVsun, results in AIDS. The extent of plasma
      viremia in pathogenic infection is an excellent prognostic indicator of clinical
      course, with higher viral load being predictive of shorter survival and low
      viremia being predictive of long-term non-progression. Based upon this paradigm,
      one would have expected naturally infected animals to exhibit low levels of
      viremia. In reality, AGMs, SMs, mandrills and chimpanzees infected naturally with
      their own unique viruses display moderate to high levels of plasma viremia. A
      significant reduction in CD4+ T-cells in infected versus uninfected SMs suggests
      that the virus may be cytopathic to some degree. These infected animals still
      maintain adequate CD4+ T-cells over their entire life in captivity. A distinct
      characteristic of natural infection is the lack of immunopathology as
      demonstrated by normal lymph node morphology, lower expression of activation and
      proliferation markers on CD4+ T-cells, and a generally muted immune response to
      the virus. Naturally infected SMs and AGMs clearly mount antiviral cellular and
      humoral immune responses. Therefore, models suggesting immune tolerance to SIV
      are far too simplistic to explain the lack of disease in these animals. It is
      probable that a unique balance between T-cell renewal and proliferation and loss
      through activation-induced apoptosis, and virus-induced cell death has been
      achieved in SMs and AGMs. The study of the dynamics of T-cell production,
      proliferation and cell death in asymptomatic natural infection should, therefore,
      yield insights into the pathogenesis of AIDS.

PMID- 15168741
TI  - Lost in translation: implications of HIV-1 codon usage for immune escape and drug
      resistance.
AB  - Synonymous nucleotide substitutions in protein-coding sequences are often
      regarded as evolutionarily neutral and not subject to selective pressure.
      However, synonymous codons can sometimes lead to different patterns of amino acid
      substitution by single nucleotide changes. Based on the deconstruction of the
      standard genetic code, we propose the term 'quasi-synonymous' to describe codons
      that specify the same amino acid, but lie on different mutational pathways, and
      we show that in at least one rapidly evolving organism, HIV-1, quasi-synonymy
      plays a role in its evolution. We present concrete examples that demonstrate the
      relevance of codon usage in the development of antiretroviral-drug resistance. In
      the case of the host immune response, the data indicates that viral evasion is
      achieved through use of codons that lie on the direct path to escape mutants, and
      equally, permit rapid reversion to wild-type in the absence of these selective
      pressures. Quasi-synonymy conditions HIV-1 and, potentially, other rapidly
      evolving organisms in their exploration of the mutational space.

PMID- 15168742
TI  - Discontinuation of the clinical development of fusion inhibitor T-1249.

PMID- 15168743
TI  - Treatment of hepatitis C in HIV-coinfected patients at the CROI.

PMID- 15168744
TI  - Follistatin alters myostatin gene expression in C2C12 muscle cells.
AB  - The objective of the present study was to determine the effects of follistatin
      addition on myostatin and follistatin gene expression patterns in C2C12 muscle
      cells. C2C12 cells were administered with 100 ng/ml recombinant human (rh)
      follistatin in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal
      bovine serum (FBS), 4 mM glutamine and antibiotics daily for three days. Rh
      follistatin was not added in the control wells. Follistatin and myostatin gene
      cDNAs were synthesised by reverse transcriptase polymerase chain reaction (RT
      PCR). The time course of follistatin gene expression pattern was similar in both
      the control and the follistatin-treated group. Myostatin mRNA level significantly
      increased in the follistatin-treated group after 24 h of culture (Fig. 3, P <
      0.01). Amounts then sharply decreased (Fig. 3, P < 0.01) at 48 h of culture,
      whereas there was no significant difference between the control and the
      follistatin-treated group at 72 h of culture. Our results demonstrated that
      myostatin and follistatin mRNA were expressed in C2C12 cells and rh follistatin
      changed the myostatin expression pattern.

PMID- 15168745
TI  - Isolation and characterisation of Mycobacterium avium and Rhodococcus equi from
      granulomatous lesions of swine lymph nodes in Slovenia.
AB  - Granulomatous lesions in bovine and especially swine lymph nodes are still
      frequently observed during routine veterinary meat inspections even though
      Mycobacterium bovis infections are no longer detected in domestic animals in
      Slovenia. Different lymph nodes of pigs (n = 260) were investigated using
      classical bacteriological and molecular methods. Mycobacterium avium alone was
      isolated in 47.3% of pigs and in mixed infection with Rhodococcus equi in 3.9% of
      pigs. R. equi alone was isolated in 27.3% and in mixed infection with
      mycobacteria other than M. avium in 1.5% of pigs. A total of 133 M. avium
      isolates were typed using the IS1245, IS901 and FR300 PCR. Almost two thirds
      (60.9%) of isolates belonged to M. avium hominissuis (IS901-, IS1245+ genotype),
      33.8% of isolates belonged to M. avium avium (IS901+, IS1245+ genotype) and 5.3%
      of isolates remained non-typed. Fifty out of 85 R. equi isolates were tested for
      the virulence-associated antigens (VapA and VapB). Nearly two thirds (60.0%) were
      positive for VapB while all the other isolates were VapA- and VapB-negative.

PMID- 15168746
TI  - Leukocyte subsets and specific antibodies in pigs vaccinated with a classical
      swine fever subunit (E2) vaccine and the attenuated ORF virus strain D1701.
AB  - Total white blood cell (WBC) counts and percentages of CD4a+, CD8a+, CD5a+,
      CD45RA+, CD45RC+, wCD21+ and SWC3a+ cells in the peripheral blood of pigs were
      analysed in this study. Blood samples were collected before and on days 4, 10, 21
      and 28 after vaccination. Group 1 pigs were vaccinated with a subunit E2 vaccine
      (gp E2 32 microg/dose), and Group 2 received a subunit vaccine combined with an
      attenuated ORF virus strain D1701 10(6.45) TCID50/dose. Control pigs received a
      placebo. The total WBC count and percentage of particular cell types were within
      the normal range in vaccinated and control pigs. Although the mechanism of
      attenuated ORF virus activity is not clear, changes were observed in CD4a+,
      CD5a+, CD8a+, CD45RA+ and CD45RC+ cells in pigs that received the combination of
      a subunit vaccine and ORF virus. However, the percentage of wCD21+ and SWC3a+ did
      not differ significantly from that recorded in pigs given only the subunit
      vaccine. At days 4 and 10 the number of pigs positive to E2 antibodies was higher
      in the group that received the subunit vaccine and ORF virus than in pigs
      vaccinated with the subunit vaccine only. A higher percentage of memory cells
      (CD45RC+) as well as Th and Tc lymphocytes in pigs that received the ORF virus
      and the subunit vaccine could be ascribed to a nonspecific influence of the ORF
      virus on the development (through cognate interactions between T and B cells) and
      the duration (presumed according to the finding of the clonal expression of
      memory cells) of humoral immunity (assessed by a higher number of seropositive
      pigs in this group). This seems likely since the proportion of these cells was
      found to be lower in the pigs that received E2 vaccine only.

PMID- 15168747
TI  - A survey of the prevalence of infectious bronchitis virus type 4/91 in Iran.
AB  - To evaluate the prevalence of infectious bronchitis virus (IBV) type 4/91 in
      Iran, tracheal swabs from 77 broiler flocks in 16 provinces were collected at the
      slaughterhouse. Swabs were subjected to RNA extraction and tested by RT-PCR,
      followed by a type-specific nested PCR. The viral RNA was detected in 33 samples
      (42.8%) from different provinces. The results indicate a relatively high
      prevalence of IBV type 4/91 in Iran and necessitate revising the vaccination
      programme against this disease.

PMID- 15168748
TI  - Detection of infectious laryngotracheitis virus in trigeminal ganglia by avidin
      biotin complex method in chickens: short communication.
AB  - Detection of infectious laryngotracheitis virus (ILTV) by avidin-biotin complex
      (ABC) method was studied in trigeminal ganglia (TRG) during the acute and post
      acute or latent period in chickens inoculated with an A96 strain of the antigen.
      TRG tissue samples were collected from uninoculated (10 chickens) and inoculated
      (30 chickens) animals at various intervals post inoculation (PI), and stained by
      the ABC method. The results indicated that no ILTV antigen was detected in the
      TRG between PI days 3 and 11. However, the antigen was detected in most of the
      chickens between PI days 13 and 41. It is concluded that the ABC method can be
      used successfully for the detection of ILTV antigens in TRG during post-acute or
      latent period.

PMID- 15168749
TI  - Correlations among the somatic cell count of individual bulk milk, result of the
      California Mastitis Test and bacteriological status of the udder in dairy cows.
AB  - In a survey of about 3000 dairy cows producing low somatic cell count (SCC) milk
      and kept on a large-scale dairy farm, California Mastitis Test (CMT) positivity
      was found in 2714 udder quarters of 1491 cows. Pathogenic microorganisms were
      isolated from 57.6% of these 2714 udder quarters during bacteriological
      examination. The commonest pathogens were coagulase-negative staphylococci (CNS,
      41%) and Staphylococcus aureus (32.5%); however, udder infections caused by
      environmental streptococci (12.8%) and coliform bacteria (6.8%) were also common.
      All pathogens resulted in a significant increase of the SCC in individual bulk
      milk (IBM) samples. In the case of CNS, this SCC elevation in IBM was
      significantly lower than in the case of infection by the other pathogens. In
      spite of this, because of the high number of udder infections caused by CNS, the
      adverse effect exerted by CNS on dairy herds is considered to be substantial. It
      was found that 54.6% of all CMT-positive cows produced IBM of an SCC below 400
      thousand per ml. The milk produced by 41% of the 315 cows excreting S. aureus
      also had an SCC below 400 thousand per ml. This poses a serious risk of infection
      to the healthy herdmates. At the same time, 11% of the infected cows produced IBM
      with an SCC below 100 thousand per ml. On the basis of these findings, only the
      regular analysis of SCC of IBM can be a reliable indicator of chronic
      intramammary infection. As the SCC of milk produced by CMT-positive cows (and
      especially of those excreting pathogens) tended to increase with advancing
      lactation, the authors suggest that an efficient drying-off therapy should be
      used to restore udder health and, whenever justified, culling of cows cannot be
      avoided either.

PMID- 15168750
TI  - Effects of nickel supply on the fattening performance and several biochemical
      parameters of broiler chickens and rabbits.
AB  - Broiler chicken and rabbit experiments were carried out to study the effects of
      nickel (Ni) supplementation on growth performance and Ni metabolism. ROSS
      cockerels and New Zealand White female rabbits were fed a diet containing Ni in
      concentrations of 0, 50 and 500 mg/kg in dry matter (DM). Dietary supplementation
      of 50 mg Ni/kg slightly improved the body weight gain (BWG) and had a beneficial
      effect on the feed conversion efficiency (FCE) in broiler chickens. However, Ni
      added at a level of 500 mg/kg significantly (P < 0.05) reduced the BWG by 10% and
      resulted in significantly (P < 0.05) worse (2.3 +/- 0.2 kg/kg) FCE. The relative
      weight of the liver in cockerels was significantly (P < 0.05) decreased by Ni as
      compared to the control group (1.7 and 2.1% vs. 2.6%). The activity of AST and
      CHE enzymes was increased insignificantly by dietary supplementation of 500 mg
      Ni/kg, indicating damage of the liver parenchyma. The results of serum
      biochemistry were confirmed by a mild or moderate form of pathological focal
      fatty infiltration of the liver in broilers. Supplemental Ni of 50 mg/kg
      concentration resulted in non-significantly increased BWG in rabbits. Ni added to
      the diet at a level of 500 mg/kg reduced the digestibility of crude protein by 3
      4% and that of crude fibre by 20-25% in rabbits. Approx. 98% of the ingested Ni
      was lost from the body via the faeces, 0.5-1.5% via the urine and approx. 1% was
      incorporated into the organs of rabbits. As a result of dietary supplementation
      of 50 and 500 mg Ni/kg, Ni accumulated in the kidneys (4.9 +/- 0.5 and 17.1 +/-
      3.1 vs. 1.9 +/- 0.3 mg/kg DM), ribs (10.3 +/- 0.4 and 10.4 +/- 0.6 vs. 9.1 +/-
      0.6 mg/kg DM), heart (1.4 +/- 0.2 and 2.5 +/- 0.4 vs. 1.0 +/- 0.1 mg/kg DM) and
      liver (1.3 +/- 0.1 and 2.2 +/- 0.2 vs. 0.9 +/- 0.05 mg/kg DM), as compared to the
      control animals. It can be stated that supplementation of the diet with 50 mg
      Ni/kg had slight but non-significant beneficial effects on the growth performance
      of broiler chickens and rabbits.

PMID- 15168751
TI  - Effect of inorganic and organic manganese supplementation on the performance and
      tissue manganese content of broiler chicks.
AB  - The effects of dietary levels of manganese (Mn) in inorganic (MnO) and organic
      (Mn fumarate) forms were evaluated on cockerel chicks. A basal corn-soybean diet
      with 23 mg/kg Mn was supplemented with levels of 0, 30, 60 and 240 ppm Mn from
      both Mn sources. Each treatment was replicated in five pens of 10 chicks. The
      chicks were fed diets ad libitum from 14 to 49 days of age, after which five
      birds per treatment were sacrificed for pathomorphological examinations and
      analysis. The treatments did not exert significant effects on the body weight
      (BW), the feed/gain (F/G) ratio or the mortality rate. According to the necropsy
      findings, no growth retardation or emaciation occurred in either of the groups
      and the differences in the average absolute and relative organ weights were not
      significant (P > 0.05). Tissue analysis indicated that the tibia showed the
      greatest response to Mn, followed by the liver and kidney. Accumulation in the
      tibia was higher (P < 0.05) with supplements of 30, 60 and 240 mg/kg from both Mn
      sources (3.71, 3.78, 4.44, and 3.68, 4.00, 4.36 mg/kg DM, MnO and Mn fumarate,
      respectively) compared to the control group (3.21 mg/kg). Accumulation in the
      liver increased significantly (P < 0.05) only with supplements of 60 and 240 ppm
      independently of the Mn source (12.7, 14.2, and 14.0, 14.9 mg/kg, respectively)
      compared to the control (9.8 mg/kg). Similarly, kidney tissue Mn was higher (P <
      0.05) only with supplements of 60 and 240 ppm (12.8, 12.8, and 13.1, 12.5 mg/kg,
      respectively) compared to the control (10.2 mg/kg). At the same level of
      supplementation of the two Mn sources there were no significant differences (P >
      0.05) between the Mn concentrations of organs and tissues. Droppings sensitively
      reflected the intake, whereas blood plasma and feathers showed only the extreme
      Mn loading.

PMID- 15168753
TI  - Health status of free-living pigeons (Columba livia domestica) in the city of
      Ljubljana.
AB  - In the year 2000 an epidemiological research was undertaken on the health status
      of free-living pigeons in the city of Ljubljana, Slovenia. A total of 139 pigeons
      were captured and examined for the most common bacterial, viral, and parasitic
      diseases. Serum samples, oropharyngeal and cloacal swabs as well as samples of
      droppings and feathers were taken from the captured birds. Antibodies to
      paramyxovirus type 1 were found in 84.2% of the sera examined, and 23.7% of birds
      were serologically positive to Chlamydophila psittaci. Antibodies to avian
      influenza virus were not detected. Salmonella spp. were isolated from 5.7% of the
      cloacal swabs. Trichomonas gallinae was clinically suspected and then
      microscopically confirmed using oropharyngeal swabs in 7.9% of examined birds.
      Eimeria spp. was identified in 71.9%, Capillaria sp. in 26.6% and Ascaridia
      columbae in 4.3% of droppings samples examined. Of the ectoparasites, Columbicola
      columbae and Campanulotes bidentatus compar were found.

PMID- 15168752
TI  - Marek's disease vaccination, with turkey herpesvirus, and enrofloxacin modulate
      the activities of hepatic microsomal enzymes in broiler chickens.
AB  - Chickens were vaccinated against Marek's disease intramuscularly at one day of
      age. Enrofloxacin was given ad libitum in the drinking water at concentrations of
      50, 100 and 250 mg/L from 8 days to 13 days of age when the animals were killed
      and the activities of cytochrome P-450 enzymes in the liver were measured.
      Vaccinated non-treated chickens served as a positive control. A negative control
      group was neither vaccinated nor treated. Vaccination decreased the activity of
      aniline hydroxylase and ethylmorphine N-demethylase in the positive control
      group. Subsequent application of enrofloxacin in the lowest concentration (50
      mg/L) decreased, while that given at the highest level (250 mg/L) significantly
      increased the activity of the same microsomal enzymes. Relative liver weights and
      concentrations of proteins in 9000 x g supernatant were not affected by
      vaccination or treatment.

PMID- 15168754
TI  - Determination of the rate of true fertility in duck breeds by the combination of
      two in vitro methods.
AB  - Embryonic mortality is a significant problem plaguing the hatching success. Its
      early forms are especially hardly distinguishable from true infertility.
      Propidium iodide (PI) staining of the germinal disc combined with outer
      perivitelline layer (OPVL) sperm counting was used for the determination of
      'true' fertility of duck eggs in two different experiments: fertility
      investigation on fresh, unincubated eggs of Hungarian ducks and on incubated eggs
      of a crossbred, selected as 'infertile' at the 7th day of incubation. Examination
      of the relationship between OPVL sperm count and fertility seems to be an
      adequate tool for checking the effectiveness of insemination programmes and the
      fertilising capacity of poultry spermatozoa. The proportion of fertile eggs was
      around 50% when the number of OPVL sperm was between 0.1 and 0.2 spermatozoa/mm2.
      Ninety-nine percent of the eggs containing > 0.3 OPVL sperm/mm2 were fertile and
      all of the eggs containing < 0.05 sperm/mm2 were infertile. To assure the
      accuracy of fertility prediction by OPVL sperm counting, PI staining of the
      germinal disc was used to determine fertility in uncertain cases. Identification
      of very early embryonic mortality, i.e. that occurring before oviposition, is
      very difficult. The use of a dissecting microscope for the assessment of real
      fertility is suitable in most of the cases, while PI staining of the germinal
      discs proved to be more reliable for detecting very early embryonic death. The
      combination of the two methods proved to be a useful tool for detecting the
      'true' fertility of duck eggs of different breeds.

PMID- 15168755
TI  - Tracking of the hormonally induced maturation of female eels by computed
      tomography.
AB  - Female European eels were kept in artificial seawater for a trial period of 14
      weeks. Three fish were injected intra-abdominally with carp pituitary suspension
      (twice a week) and human chorionic gonadotropin (every 2nd week), with the aim to
      induce artificial maturation. Three further fish were not treated (control). Fish
      were not fed during the trial. The treated fish were scanned by computed
      tomography (CT) every second week (the controls only at the start and at the end
      of the trial) to follow changes in body composition. Notable decreases were shown
      in total body pixel number (body volume), total body fat content, total fillet
      volume and fillet fat content during the experiment. Changes were more pronounced
      in the treated group than in the control. The abdominal volume strongly increased
      in the responding fish throughout the trial. The ovary volume increased
      measurably, while its fat content increased only until the 8th week, after which
      a decrease was measured. Tissue volumetric estimations of the ovary were also
      supported by histological results. A so-called volumetric gonadosomatic index
      (gonad volume/total body volume x 100) was developed for the quantitative
      characterisation of eel maturation.

PMID- 15168757
TI  - [For the prevention of medical malpractice--the current status and the proposal].

PMID- 15168758
TI  - [Recent progress in diagnosis of early colorectal cancer].

PMID- 15168759
TI  - [Advances of an internal treatment for early colorectal carcinoma].

PMID- 15168756
TI  - Comparison of femoral inclination angle measurements in dysplastic and
      nondysplastic dogs of different breeds.
AB  - In this study, inclination angle of the femoral head and neck was measured on 484
      limbs of 242 dogs belonging to 7 breeds, examined for hip dysplasia. These
      inclination angles were compared according to age, sex and joint laxity,
      evaluated with Subluxation Index (SI) and Norberg angle (NA) results. The
      findings indicate that (a) there was a minimal (nonsignificant) difference in
      femoral inclination angle between the dysplastic and nondysplastic dogs belonging
      to 7 breeds; (b) although there was no significant difference in femoral
      inclination angle between the nondysplastic dogs belonging to 4 breeds (Pointer,
      Irish Setter, Golden Retriever and German Shepherd), a significant difference was
      observed between Doberman and Labrador, and between Anatolian Karabash and the
      other six breeds (p < 0.001). Age and sex did not affect the femoral neck angle.

PMID- 15168760
TI  - [Advancement of laparoscopic surgery for early colorectal cancer].

PMID- 15168761
TI  - [A case of gastric metastasis of small cell cancer of the lung, regression of the
      gastric lesion after chemotherapy].

PMID- 15168762
TI  - [A case of the rupture of gastroduodenal artery aneurysm by penetration to the
      duodenum, successfully treated with transcatheter arterial embolization].

PMID- 15168763
TI  - [A case of liver cirrhosis B resistant to lamivudine showing the clinical effect
      of adefovir dipivoxil].

PMID- 15168764
TI  - [A case of gastroepiploic arteriovenous malformation causing massive
      intraperitoneal hemorrhage].

PMID- 15168765
TI  - A new strategy for the attenuation of left ventricular pressure gradient in
      patients with HOCM.

PMID- 15168766
TI  - "Takotsubo" cardiomyopathy A syndrome characterized by transient left ventricular
      apical ballooning that mimics the shape of a bottle used for trapping octopus in
      Japan.

PMID- 15168767
TI  - Hypereosinophilic syndrome vs eosinophilic gastroenteritis.

PMID- 15168769
TI  - Hepatic hydrothorax in the absence of ascites diagnosed by intraperitoneal
      spraying of indocyanine green.
AB  - Hepatic hydrothorax in the absence of ascites is a rare complication of liver
      cirrhosis. A 56-year-old woman was referred to our hospital because of a massive
      pleural effusion on the right side, requiring continuous drainage. Although the
      patient was known to have chronic hepatitis C, she had no signs of hepatic
      failure including ascites. A laparoscopic examination revealed a nodular liver
      and a small volume of ascites in the peritoneal cavity. Indocyanine green sprayed
      into the intraperitoneal cavity was excreted from the pleural drain just after
      the spraying, indicating an intraperitoneal origin of the pleural fluid.
      Discontinuation of pleural drainage and an introduction of standard treatment for
      ascites due to liver cirrhosis (including restriction of salt intake and diuretic
      administration) resulted in a marked decrease of pleural effusion.

PMID- 15168768
TI  - Hepatocellular carcinoma in a patient with liver cirrhosis associated with
      negative serum HCV tests but positive liver tissue HCV RNA.
AB  - A 70-year-old woman was admitted to our hospital because of a liver tumor.
      Laboratory data revealed mild liver dysfunction. Neither serum anti-HCV antibody
      nor HCV-RNA was detected. Computed tomography revealed a tumor lesion measuring 2
      cm in diameter within the liver. Histological examination of the tumor revealed
      moderately differentiated hepatocellular carcinoma while the non-tumorous liver
      tissue demonstrated liver cirrhosis. By the RT-PCR method, HCV-RNA was detected
      from the non-tumorous liver tissue. We herein report a very rare case of
      hepatocellular carcinoma in a patient with liver cirrhosis associated with
      negative serum HCV findings, but positive finding for liver tissue HCV RNA.

PMID- 15168770
TI  - Nonalcoholic steatohepatitis with improved hepatic fibrosis after weight
      reduction.
AB  - A 65-year-old woman was admitted to our hospital for an investigation of liver
      dysfunction. She had mild obesity with hyperlipidemia, but no history of alcohol
      abuse. Other known causes of liver dysfunction, such as viruses, autoimmunity and
      drug effects, were excluded. The liver histology was consistent with nonalcoholic
      steatohepatitis (NASH). After diagnosis of NASH, the patient started diet and
      exercise therapy and, in parallel with weight reduction, her liver function
      improved. One year after the therapy, a liver biopsy showed that steatosis,
      necroinflammation and even fibrosis were improved. Hence, here we report a case
      of NASH in which weight reduction was effective in improving both biochemical and
      histological findings.

PMID- 15168772
TI  - An atypical case of "Takotsubo cardiomyopathy" during alcohol withdrawal:
      abnormality in the transient left ventricular wall motion and a remarkable
      elevation in the ST segment.
AB  - A 64-year-old man was admitted due to hypokalemia-related myopathy. He was heavy
      drinker. He felt the stress of alcohol withdrawal during his hospitalization. The
      patient suffered a cardiopulmonary arrest lasting approximately 5 minutes on the
      fifth hospital day. One day later, ST-segment elevation was observed in leads I,
      aV(L), and V(2-6). Emergent cardiac catheterization was performed for suspicion
      of acute myocardial infarction. Normal coronary arteries with anterior akinesis
      of the left ventricle were revealed during the procedure. The present case may be
      an atypical form of "Takotsubo cardiomyopathy" in which the left ventricular
      contraction is due to focal anterior wall motion abnormalities.

PMID- 15168771
TI  - Improved hypertrophic obstructive cardiomyopathy by left ventricular apex
      epicardial pacing.
AB  - We report a case of severe hypertrophic obstructive cardiomyopahy (HOCM) that was
      markedly improved by left ventricular (LV) apex epicardial pacing. A 55-year-old
      woman with HOCM had suffered from dyspnea. Cardiac catheter examination showed a
      resting pressure gradient across the LV outflow tract of 198 mmHg despite
      combined medication. During the examination, right dual-chamber pacing could not
      sufficiently reduce the pressure gradient. Therefore, we treated the patient with
      LV apex epicardial pacing. The procedure decreased the pressure gradient to 10
      mmHg. Clinical symptoms were markedly improved. LV apex epicardial pacing may be
      an alternative therapy for patients with HOCM who are refractory to other medical
      treatment.

PMID- 15168773
TI  - Thyroid hemiagenesis with postpartum silent thyroiditis.
AB  - A 28-year-old woman with thyroid hemiagenesis, who had been diagnosed as having
      Graves' disease, became pregnant during the course of methimazole treatment. The
      treatment was terminated in the second trimester. She delivered a normal infant
      at full term. She became thyrotoxic 3 months after the delivery, hypothyroid 6
      months after the delivery, and finally euthyroid 11 months after the delivery
      without undergoing any treatment. This clinical course indicates that she
      developed silent thyroiditis after the delivery. A diagnosis of thyroid
      hemiagenesis was made on the basis of ultrasonography of the thyroid and 99mTc
      pertechnetate thyroid scintiscan.

PMID- 15168775
TI  - Emphysematous cystitis with severe hemorrhagic anemia resulting from diabetes
      mellitus type 2.
AB  - A 48-year-old woman suffering from hematuria was admitted to our hospital due to
      conscious disturbance. She had lower abdominal phantom tumor, anemia, renal
      dysfunction, hyperglycemia, metabolic acidosis and electrolyte abnormalities.
      Because of pelvocaliceal dilatation noted on abdominal ultrasonography, we first
      diagnosed her as having postrenal failure. With massive blood clots and gas
      emission from her urethra upon attempting cystoscopy, the remarkable expansion of
      the urinary bladder and a three-layered structure of gas, urine and complex of
      blood and debris inside her urinary bladder noted on abdominal CT scan, as well
      as the increased white blood cell count, we finally concluded our diagnosis as
      emphysematous cystitis.

PMID- 15168774
TI  - Primary hyperparathyroidism associatiated with aldosterone-producing
      adrenocortical adenoma and breast cancer: relation to MEN1 gene.
AB  - A rare case of primary hyperparathyroidism associated with primary aldosteronism
      and breast cancer is reported. A 44-year-old woman was admitted to our hospital
      to undergo surgical removal of breast cancer. She had hypertension with low serum
      potassium, and slightly but significantly elevated serum calcium levels. Further
      studies demonstrated an enlarged left superior parathyroid gland and a left
      aldosterone-producing adrenocortical adenoma. Blood pressure was controlled with
      spironolactone and nifedipine, and left mastectomy was done for breast cancer.
      The pathological diagnosis was scirrhous breast carcinoma. Although the
      postoperative course was uneventful, her serum calcium gradually and
      progressively rose to higher levels. Left superior parathyroidectomy and left
      adrenalectomy were then performed simultaneously. The pathological diagnoses of
      the resected parathyroid gland and adrenal gland were parathyroid chief cell
      adenoma and adrenocortical adenoma with hyperplasia of zona glomerulosa,
      respectively. To clarify if the occurence of these tumors may be related to MEN1
      gene mutations, we analyzed MEN1 gene in this patient, and found a loss of
      heterozygosity of the MEN1 locus in the parathyroid adenoma and breast cancer.
      Thus, we conclude that an alteration of the MEN1 gene and/or another tumor
      suppressor gene located at the MEN1 locus on chromosome 11q13 may be responsible
      for the development of parathyroid adenoma and breast cancer in our patient
      suggesting that the clinical spectrum of MEN1 might include breast cancer. In
      addition, serum calcium should be interpreted with caution in primary
      aldosteronism, because hypercalcemia may be masked in the presence of aldosterone
      excess.

PMID- 15168776
TI  - Left lumbar subcutaneous cold abscess with tuberculous spondylitis.
AB  - We report a 29-year-old man with a rare left lumbar subcutaneous cold abscess
      complicated by tuberculous spondylitis during the treatment of pulmonary
      tuberculosis. Pulmonary tuberculosis was rapidly improved by anti-tuberculous
      drugs, however curative operation for tuberculous spondylitis was necessary after
      18 months because tuberculous spondylitis was overlooked. Imaging techniques are
      important in helping to establish a diagnosis of tuberculous spondylitis. It
      should be stressed that a high clinical index of suspicion for tuberculosis is
      needed to correctly diagnose this disease.

PMID- 15168777
TI  - Pulmonary lymphoepithelioma-like carcinoma: predominant infiltration of tumor
      associated cytotoxic T lymphocytes might represent the enhanced tumor immunity.
AB  - Lymphoepithelioma-like carcinoma (LELC) of the lung is an undifferentiated
      carcinoma with prominent lymphoid stroma. We encountered a case of synchronous
      primary lung cancers of LELC and papillary adenocarcinoma in a 67-year-old
      Japanese woman. By in situ hybridization, Epstein-Barr virus (EBV) genome was
      detected in malignant epithelial cells of LELC but not in the papillary
      adenocarcinoma. Tumor-infiltrating lymphocytes in LELC were predominantly CD8+
      and T cell intracytoplasmic antigen (TIA-1)+ cytotoxic T cells with closely
      associated with HLA-DR-positive LELC cells by double immunostaining. These data
      indicate that the exaggerated lymphoid infiltration in and around the EBV
      infected carcinoma cells may represent the enhanced tumor immunity, suggesting a
      better prognostic indicator.

PMID- 15168778
TI  - Pulmonary dirofilariasis with serologic study on familial infection with
      Dirofilaria immitis.
AB  - An asymptomatic patient with a pulmonary coin lesion surgically diagnosed with
      pulmonary dirofilariasis caused by infection with Dirofilaria immitis (D.
      immitis) is presented. The preoperative stored serum of the patient was positive
      for D. immitis by enzyme-linked immunosorbent assay (ELISA). A family study
      showed that three of five family members were seropositive for D. immitis. These
      results suggest that family members of a patient with pulmonary dirofilariasis
      were frequently exposed to D. immitis and serodiagnostic methods are useful for
      detecting subclinical infection of D. immitis.

PMID- 15168779
TI  - Microscopic polyangiitis associated with diffuse panbronchiolitis.
AB  - There are several case reports of systemic vasculitis associated with chronic
      suppurative lung diseases. We describe a 46-year-old female, previously diagnosed
      as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea.
      Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA.
      Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy
      specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed
      as having ANCA-associated vasculitis, and more specifically, microscopic
      polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse
      therapy, followed by intravenous cyclophosphamide. This case suggested a possible
      association with chronic bacterial infection, which may play a role in the
      pathogenesis of ANCA-associated vasculitis.

PMID- 15168780
TI  - A rare case of idiopathic hypereosinophilic syndrome involving the oral cavity
      associated with the esophagus and gastrointestinal tract.
AB  - We report the rare case of HES involving oral cavity associated with esophagus,
      and gastrointestinal tract, which we succeeded in diagnosing precisely through a
      biopsy specimen obtained from the lip. A 64-year-old man had dysphagia, swelling
      of the oral mucosa and the posterior cervical muscles, accompanied by an
      abdominal pain and diarrhea. Peripheral blood cell count showed marked
      eosinophilia. Computed tomography showed thickening of posterior wall of the
      pharynx, esophagus, and gastrointestinal tract. Histologic specimen obtained from
      the lower lip demonstrated a moderate infiltration of eosinophils. His clinical
      condition was improved by oral prednisolone therapy.

PMID- 15168782
TI  - Decrease in left ventricular diastolic function in bedridden patients.

PMID- 15168781
TI  - Significant liver injury with dual positive IgM antibody to Epstein-Barr virus
      and cytomegalovirus as a puzzling initial manifestation of infectious
      mononucleosis.
AB  - A 35-year-old man was admitted because of significant hepatic dysfunction with
      mild splenomegaly and intra-abdominal lymphadenopathy of unknown cause.
      Infectious mononucleosis was suggested by subsequently detected high fever,
      pharyngotonsillitis and cervical lymphadenopathy, but IgM to Epstein-Barr virus
      (EBV) and cytomegalovirus (CMV) showed dual positivity. A definite diagnosis of
      EBV-induced infectious mononucleosis was established 3 months later on the basis
      of seroconversion to Epstein-Barr nuclear antigen (EBNA)-IgG positivity and
      reduced CMV-IgM titer with persistently negative CMV-IgG. This case highlights
      the initial diagnostic difficulties of EBV-induced infectious mononucleosis
      particularly in older patients, due to concomitant abnormal humoral immunity and
      unusual initial manifestations such as significant liver injury and extensive
      intra-abdominal lymphadenopathy.

PMID- 15168783
TI  - Liver involvement in catastrophic antiphospholipid syndrome.

PMID- 15168784
TI  - Non-herpetic acute limbic encephalitis: a new subgroup of limbic encephalitis?

PMID- 15168785
TI  - Formulation and evaluation of limonene-based membrane-moderated transdermal
      therapeutic system of nimodipine.
AB  - The aim of the present study was to design a membrane-moderated transdermal
      therapeutic system (TTS) of nimodipine using 2% w/w hydroxypropyl methylcellulose
      (HPMC) gel as a reservoir system containing 4% w/w of limonene as a penetration
      enhancer. The permeability flux of nimodipine through ethylene vinyl acetate
      (EVA) copolymer membrane was found to increase with an increase in vinyl acetate
      content in the copolymer (9 to 28%). The effect of pressure-sensitive adhesives
      such as TACKITE A 4MED on the permeability of nimodipine through EVA membrane
      2825 (28% w/w vinyl acetate) or membrane/rat skin composite also was studied. The
      permeability flux of nimodipine from the chosen EVA 2825 (with 28% vinyl acetate
      content) was 159.72 +/- 1.96 microg/cm2/hr, and this flux further decreased to
      141.85 +/- 1.54 microg/cm2/hr on application of pressure-sensitive adhesive
      (TACKWHITE A 4MED). However, the transdermal permeability flux of nimodipine
      across EVA 2825 membrane coated with TACKWHITE A 4MED/rat skin composite was
      found to be 126.59 +/- 2.72 microg/cm2/hr, which is 1.3-fold greater than the
      required flux. Thus, a new transdermal therapeutic system for nimodipine was
      formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive
      TACKWHITE 4A MED and 2% w/w HPMC gel as reservoir containing 4% w/w of limonene
      as a penetration enhancer. The bioavailability studies in healthy human
      volunteers indicated that the TTS of nimodipine, designed in the present study,
      provided steady-state plasma concentration of the drug with minimal fluctuations
      for 20 hr with improved bioavailability in comparison with the immediate release
      tablet dosage form.

PMID- 15168786
TI  - Transepithelial electrical resistance is not a reliable measurement of the Caco-2
      monolayer integrity in Transwell.
AB  - The significance of monitoring transepithelial electrical resistance (TEER) value
      during the study on drug absorption through Caco-2 monolayers in Transwells was
      re-evaluated. TEER value was monitored before, during, and after the absorption
      of Streptokinase (45 KD). Four enhancers--disodium ethylenediaminetetracetate
      (disodium EDTA), sodium cholate (NaC), sodium taurocholate (NaTC), and sodium
      caprate along with alpha-hemolysin (a cell membrane pore-forming toxin)--were
      used to signify the outcome of this study. Modified trypan blue exclusion
      technique was used to examine the Caco-2 cell viability throughout the absorption
      studies. The enhancers at the used concentration exhibited toxic effect on the
      Caco-2 cells as evident from the trypan blue exclusion studies. This toxic effect
      was not reflected by the TEER profile because TEER value dropped after the
      addition of the absorption enhancers. But it came back to its initial value after
      the cell culture media was replaced by enhancer-free media. This toxic effect was
      confirmed by the antiproliferation studies on the four enhancers and alpha
      hemolysin against Caco-2 cells. Therefore, we concluded that the measurement of
      TEER is not a reliable method to determine the absorption enhancers toxicity or
      integrity of the Caco-2 monolayers in the Transwells.

PMID- 15168787
TI  - Synthesis and alkylation activity of a nitrogen mustard agent to penetrate the
      blood-brain barrier.
AB  - Nitrogen mustard agents are widely used for the clinical treatment of cancers. A
      nitrogen mustard (N-mustard) agent was synthesized utilizing nicotinic acid as
      the carrier of the alkylating substituent (-OCH2CH2N(CH2CH2Cl)2) that forms an
      ester group (R-C(O)-OR) on a heterocyclic ring. The N-mustard agent is a solid at
      room temperature and is stable for more than 6 weeks when stored at -10 degrees
      C. To determine the kinetics of alkylation activity a nucleophilic primary amine
      compound (4-chloroaniline) was placed in aqueous solution with the mustard agent
      at physiological pH 7.4 (pH of blood) and 37 degrees C. The alkylation reaction
      was found to be second-order with rate equation: rate = k2[N-mustard][Nu], where
      Nu = nucleophile and k2 = 0.0415 L/(mol x min). Pharmacological descriptors
      calculated showed values indicating a strong potential of penetrating the blood
      brain barrier. The partition coefficient (Log P) of the mustard agent is 1.95
      compared with 0.58 for nicotinic acid. Values of descriptors such as dipole,
      polar surface area, Log BB, molar refractivity, parachor, and violations of Rule
      of 5 were found to be 5.057 Debye, 42.44 A2, 0.662, 72.7 cm3, 607.7 cm3, and 0.0
      for the N-mustard agent. Value of polar surface area for the mustard agent (42.44
      A2) predicts that >90% of any amount present in the intestinal tract will be
      absorbed.

PMID- 15168789
TI  - The effect of different lipid components on the in vitro stability and release
      kinetics of liposome formulations.
AB  - Liposomes are colloidal carriers that form when certain (phospho)lipid molecules
      are hydrated in an aqueous media with some energy input. The ideal liposome
      formulation with optimum stability will improve drug delivery by decreasing the
      required dose and increasing the efficacy of the entrapped drug at the target
      organ or tissue. The most important parameter of interest in this article was to
      compare the efficacy of three different liposomes formulated with DSPC, DMPC, and
      DPPC, all saturated neutral phospholipids with different acyl chain lengths and
      transition temperatures. DMPC has a phase transition temperature (Tc) below 37
      degrees C, whereas the other two phospholipids possess Tcs above the
      physiological temperature. These lipids were then added to a cholesterol
      concentration of 21% to optimize the stability of the vesicles. The liposomes
      were prepared by a sonication and incubated in phosphate buffered saline (PBS) at
      4 degrees C and 37 degrees C. The encapsulation efficiency, initial size, and
      drug retention of the vesicles were tested over a 48-hr period employing
      radiolabeled inulin as a model drug. The phase transition temperature of
      liposomes, which depends on the Tc of the constituent lipids, was an important
      factor in liposome stability. Of all the liposomes tested, the greatest
      encapsulation efficiency was found for the DSPC liposomes (2.95%) that also had
      the greatest drug retention over 48 hr at both 4 degrees C (87.1 +/- 6.8%) and 37
      degrees C (85.2 +/- 10.1%), none of these values being significantly different
      from time zero. The lowest drug retention was found for DMPC liposomes for which
      a significant difference in drug retention was seen after only 15 min at both 4
      degrees C (47.3 +/- 6.9%) and 37 degrees C (53.8 +/- 4.3%). The DPPC liposomes
      showed a significant difference in drug retention after 3 hr at 4 degrees C (62.1
      +/- 8.2%) and after 24 hr at 37 degrees C (60.8 +/- 8.9%). Following the initial
      drop at certain time intervals a plateau was reached for all of the liposome
      formulations after which no significant difference in drug retention was
      observed. In conclusion, liposomes with higher transition temperatures appear to
      be more stable in PBS either at 4 degrees C or 37 degrees C, indicating that the
      increase in acyl chain length (and therefore transition temperature) is directly
      proportional to stability.

PMID- 15168788
TI  - Transdermal drug delivery systems of a beta blocker: design, in vitro, and in
      vivo characterization.
AB  - The matrix type transdermal drug delivery systems (TDDS) of metoprolol were
      prepared by film casting technique using a fabricated stainless steel film
      casting apparatus and characterized in vitro by drug release, skin permeation,
      skin irritation, and in vivo pharmacodynamic and stability studies. Four
      formulations were prepared that differed in the ratio of matrix forming polymers.
      Formulations M-1, M-2, M-3, and M-4 were composed of Eudragit RL-100 and
      polyvinyl acetate with the following ratios: 2:8, 4:6, 6:4, and 8:2,
      respectively. All the four formulations carried 10% (w/w) of metoprolol tartrate,
      5% (w/w) of dibutylphthalate, and 5% (w/w) of (+/-) menthol in
      dichloromethane:isopropyl alcohol (80:20 v/v). Cumulative amount of drug released
      in 48 hr from the four formulations was 79.16%, 81.17%, 85.98%, and 95.04%. The
      corresponding values for cumulative amount of drug permeated for the said
      formulations were 59.72%, 66.52%, 77.36%, and 90.38%. On the basis of in vitro
      drug release and skin permeation performance, formulation M-4 was found to be
      better than the other three formulations and it was selected as the optimized
      formulation. The formulation appeared to be stable when stored at 40 degrees C
      and 75% RH with negligible degradation of the drug. The TDDS was found to be free
      of any skin irritation as suggested by skin irritation score of 1.16 (<2.00)
      under Draize score test. Statistically significant reduction in mean blood
      pressure (p < .01) was achieved in methyl prednisolone-induced hypertensive rats
      on treatment with the TDDS.

PMID- 15168790
TI  - Drug delivery devices based on mesoporous silicate.
AB  - A mesoporous material based on aluminosilicate mixture was studied to investigate
      its ability to include drugs and then release them. Nonsteroidal anti
      inflammatory agents such as diflunisal, naproxen, ibuprofen and its sodium salt
      have been used in this study. The preparation of the mesoporous material and its
      characterization by X-ray, N2 absorption-desorption isotherm, and
      thermogravimetry analysis have been described. Drug loading was performed by a
      soaking procedure. Drug-loaded matrices were characterized for entrapped drug
      amount, water absorption ability, and thermogravimetric behavior. Drug release
      studies also were performed at pH 1.1 and 6.8 mimicking gastrointestinal fluids.
      Experimental results showed that this type of matrix is able to trap the
      bioactive agents by a soaking procedure and, then, to release them in conditions
      mimicking the biological fluids. Also, the high affinity of these matrices for
      water makes them potentially biocompatible. Release data suggest that the matrix
      impregnated with diflunisal offers good potential as a system for the modified
      drug release.

PMID- 15168791
TI  - Influence of ultrasound on the percutaneous absorption of ketorolac tromethamine
      in vitro across rat skin.
AB  - The influence of ultrasound on percutaneous absorption of ketorolac tromethamine
      was studied in vitro across rat skin. Sonication was carried out with a
      continuous mode, at an intensity of 1-3 W/cm2 and a frequency of 1 MHz for 30
      min. A significant increase in permeation of ketorolac through rat skin was
      observed with the applied sonication at 3 W/cm2 when compared with permeation at
      1 and 2 W/cm2. Enhanced ketorolac penetration at 3 W/cm2 can be explained by the
      mechanical and/or thermal action of ultrasound waves. The distance of the
      ultrasound probe from the skin surface did not influence the flux of the drug.
      Pretreatment of skin by 5% d-limonene in ethanol for 2 hr followed by sonication
      at 3 W/cm2 (30 min) significantly enhanced the permeation of ketorolac when
      compared with passive flux with or without enhancer pretreatment.

PMID- 15168792
TI  - Characterization of drug release and diffusion mechanism through
      hydroxyethylmethacrylate/methacrylic acid pH-sensitive hydrogel.
AB  - Hydroxyethylmethacrylate/methacrylic acid copolymer cross-linked with
      ethylenglycol dimethacrylate was prepared by a bulk free radical polymerization
      method. The permeability studies of this pH-sensitive hydrogel to drugs with
      different water solubilities showed a water-content dependent diffusion or pore
      mechanism for ephedrine HCl (water-soluble model drug), whereas, a partition or
      solute-diffusion mechanism for indomethacin (a water-insoluble drug) was seen.
      Data analysis of release tests, according to the swelling interface number and
      Peppas equation for ephedrine HCl in pH 7.4, showed a biexponential model
      kinetic, whereas in pH 1.2 a swelling-controlled mechanism was seen. Indomethacin
      was released by an anomalous or non-Fickian release kinetics.

PMID- 15168793
TI  - An investigation into the factors influencing drug release from hydrophilic
      matrix tablets based on novel carbomer polymers.
AB  - Drug release from hydrophilic matrix tablets can be strongly influenced by the
      proportion of matrix forming polymer and the dimensions and geometry of the
      tablets. A complete two-factor, three-level factorial design, followed by
      multiple regression analysis and response surface methodology, was applied to
      investigate the influence of polymer level and tablet size on drug release
      kinetics from hydrophilic matrix tablets prepared with Carbopol 971P and Carbopol
      71G. Tablet diameter, radius-to-height ratio, tablet surface area, and surface
      area-to-volume ratio were evaluated as independent variables in terms of their
      applicability to characterize tablet size and geometry. The results indicate that
      it may be possible to control the rate of drug release by modifying the
      proportion of carbomer in tablets and tablet dimensions. The practical benefit of
      these simulations is to optimize the geometry and dimensions of a controlled
      release device and reduce the number of experiments involved in the development
      of new controlled release dosage forms.

PMID- 15168794
TI  - Methylene blue photoinactivation of RNA viruses.
AB  - We present a review of the current status of the use of methylene blue (MB)
      photoinactivation of viruses starting with the first early observations up to its
      current use to inactivate HIV-1 in blood products. Basic mechanism of action
      studies conducted with model bacteriophages indicate that MB-photomediated viral
      RNA-protein crosslinkage is a primary lesion and that oxygen, specifically
      singlet oxygen, is very important also. Basic studies on the mechanism of action
      with HIV are lacking; however, we do show new data illustrating that viral
      reverse transcriptase inactivation per se cannot account for MB-mediated
      photoinactivation. We also show data illustrating that MB photomediates the
      inactivation of West Nile Virus, a flavivirus, which poses a significant new
      threat to the continental US. MB photoinactivation of viruses show significant
      promise because the technology not only offers significant potency but the
      history of safe MB use in human therapy makes it attractive also.

PMID- 15168795
TI  - An optical thin film assay incorporating rhinovirus protease inhibitors as
      detector reagents.
AB  - Human rhinoviruses (HRV) are the main cause of the common cold. Viral replication
      utilizes the activity of the HRV3C protease (3CP) enzyme [Antimicrob. Agents
      Chemother. 43 (1999) 2444; Antimicrob. Agents Chemother. 44 (2000) 1236].
      Therefore, 3CP is an attractive target for antiviral drug development, and a new
      class of orally bioavailable irreversible 3CP inhibitors has been designed [J.
      Med. Chem. 45 (2002) 1607]. We have used related inhibitors to develop a rapid
      test for rhinovirus. The optical immuno assay (OIA) thin film detection
      technology utilizes an optically coated silicon surface to convert specific
      molecular binding events into visual color changes by altering the reflective
      properties of light through molecular thin films. The purpose of this study was
      to develop a rapid assay for the determination of 3CP combining the Thermo
      Electron Bio Star OIA technology and the newly designed inhibitor compounds. The
      advantage of this assay was in its approach, in which therapeutic and diagnostic
      targets are the same thus allowing patients with detected rhinoviruses to receive
      optimal treatment. Three different biotinylated inhibitor compounds were
      synthesized. The length of the spacer between the inhibitor and biotin core was
      5, 10, and 15 atoms. These compounds were incorporated into the OIA format for
      the HRV assay development. A rapid (20 min) OIA test was developed using a 15
      atom spacer biotinylated inhibitor (4). Forty different HRV serotypes were
      studied and thirty three serotypes of these 40 were detected (80%).

PMID- 15168797
TI  - Isolation and characterization of NMSO3-resistant mutants of respiratory
      syncytial virus.
AB  - We obtained two mutant strains of respiratory syncytial virus (RSV) which showed
      resistance against NMSO3 after 15 and 33 passages, respectively, in HEp-2 cells
      in the presence of 6.8 microM of NMSO3. The EC50 values of NMSO3 for the
      resistant virus strains were 0.48 and 0.93 microM, that is 4.8-9.3 times higher
      than that of the parent strain (EC50 = 0.1 microM). The most resistant strain
      also showed resistance against heparin but was sensitive to dextran sulfate and a
      polyoxotungstate, PM-523. In order to determine whether the acquisition of
      resistance to NMSO3 was the result of the accumulation of genetic changes of
      virus, we sequenced the G- and F-protein genes. In comparison with the standard
      type of RSV strains, we identified changes of 10 amino acids in the G protein
      including those at the central conserved segment. However, we did not observe any
      particular changes in the amino acid sequence of the F-protein of the resistant
      strains. From these results, we conclude that NMSO3 inhibits the G-protein
      interaction to the receptor. The mutations in the G-protein may result in the
      observed phenotypic resistance of RSV towards NMSO3.

PMID- 15168796
TI  - Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV
      1 primary isolates from different clades.
AB  - A new human monoclonal antibody (hmAb), designated m16, was selected by
      sequential antigen panning (SAP) of a human phage display library against
      recombinant soluble HIV-1 envelope glycoproteins (Envs) (gp140s) and their
      complexes with soluble CD4. It bound with high (nM) affinity to gp120 and gp140;
      the binding was further enhanced by interactions of the Envs with CD4. m16
      inhibited cell fusion mediated by the Envs of 9 HIV-1 isolates from clades A, B,
      E and G with potency on average comparable to that of the broadly neutralizing
      human monoclonal antibody Fab X5. The identification of a new hmAb with broad
      neutralizing activity that exhibits differential inhibitory profile suggests a
      potential for its use as a component of anti-HIV-1 treatments.

PMID- 15168798
TI  - Persistence of mutations during replication of an HIV library containing
      combinations of selected protease mutations.
AB  - It has been known that, in some cases, accumulation of specific mutations in HIV
      1 protease leads to multi-protease inhibitor (PI) resistance. We examined the
      persistence of mutations detected in HIV-1 clinical isolates cross-resistant to
      the current PIs using an HIV-1 protease restricted library (HXB2 protease in an
      HIV-1(NL4-3) background) in the absence of protease inhibitors. The virus library
      contained combinations of 0-11 amino acid substitutions (4,096 possible
      combinations) in the protease-encoding region. We examined the frequency of each
      amino acid substitution in the library using a T cell line, MT-2. The frequency
      of the amino acid substitutions V82T/I and L90M decreased rapidly with a short
      half life (t(1/2) < 10 days). However, the mutations M36I, M46I and I84V were
      relatively persistent: t(1/2) = 34.2, 28.1 and 30.6 days, respectively. Other
      amino acid substitutions, i.e., L10I, I54V, L63P, A71V and V82A, were well
      retained (t(1/2) > 36 days). By contrast, the half lives (t(1/2)) of the D30N and
      N88D mutations associated with nelfinavir (NFV) resistance were only 7.2 and 1.8
      days, respectively. These results indicate that this type of the HIV-1 protease
      restricted library is useful to evaluate the persistence of PI resistance
      associated mutations in the absence of drug selective pressure.

PMID- 15168799
TI  - In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA
      strain): differences between acyclovir and penciclovir?
AB  - Varicella-zoster virus (VZV) mutants were isolated under the pressure of
      different classes of antiviral compounds: (i) drugs that depend on the viral
      thymidine kinase (TK) for their activation, i.e. acyclovir (ACV), brivudin
      (BVDU), penciclovir (PCV) and sorivudine (BVaraU); (ii) drugs that are
      independent of the viral TK for their activation, i.e. 2-phosphonylmethoxyethyl
      (PME) derivatives of adenine (PMEA, adefovir) and 2,6-diaminopurine (PMEDAP); and
      (iii) drugs that do not require any metabolism to inhibit the viral DNA
      polymerase, i.e. foscarnet (PFA). Drug-resistant virus strains were obtained by
      serial passage of the OKA strain in human embryonic lung (HEL) fibroblasts and
      the different drug-resistant mutants were subsequently evaluated for their in
      vitro susceptibility to a broad range of antiviral drugs. Virus strains emerging
      under the pressure of ACV, BVDU and BVaraU were cross-resistant to all drugs that
      depend on the viral TK for activation, but remained susceptible to the acyclic
      nucleoside phosphonates (i.e. PMEA, PMEDAP and the 3-hydroxy-2
      phosphonylmethoxypropyl derivatives of adenine (HPMPA) and cytosine (HPMPC,
      cidofovir)) and PFA. In contrast, the virus strains selected under pressure of
      PCV were resistant to PCV, ACV, PMEA and PFA; but not BVDU, BVaraU, GCV, HPMPC or
      HPMPA. Similar patterns of drug susceptibility were noted for the virus strains
      selected under the pressure of PMEA or PFA, pointing to an alteration in the
      viral DNA polymerase as basis for the resistant phenotype selected by PCV, as
      well as PMEA and PFA. In contrast, the resistant phenotype selected by ACV as
      well as BVDU and BVaraU may be attributed primarily to mutations in the viral TK
      gene. Our data thus indicate that ACV and PCV select in vitro for different drug
      resistant VZV phenotypes; whether this is also the situation in vivo remains to
      be investigated.

PMID- 15168800
TI  - Mode of action of 2-furylmercury chloride, an anti-rhinovirus compound.
AB  - 2-Furylmercury chloride (2-FMC), an organic mercury derivative, has been found to
      inhibit the replication of all tested human rhinovirus (HRV) serotypes belonging
      to the antiviral group B and a limited number of HRV serotypes belonging to the
      antiviral group A. The mechanism of action of 2-FMC was tested against HRV-2
      (antiviral group B, minor receptor group), and compared with an antiviral
      compound for which the viral target was already determined (enviroxime). 2-FMC
      was found to bind reversibly to virus particles. However, time-dependent plaque
      reduction assays revealed that 2-FMC did not interfere with early events of HRV-2
      replication. Using a quantitative RT-PCR ELISA assay, we were able to prove that
      2-FMC inhibits the synthesis of viral RNA. However, the mode of action of 2-FMC
      is not identical to that of enviroxime, another inhibitor of viral RNA synthesis.
      Time-of-addition and time-of-withdrawal experiments demonstrated that 2-FMC acted
      during a broader time interval than enviroxime.

PMID- 15168801
TI  - Potent inhibition of respiratory syncytial virus by combination treatment with 2
      5A antisense and ribavirin.
AB  - Respiratory syncytial virus (RSV) is a major cause of lower respiratory diseases
      in infants, young children, and the elderly. Ribavirin, the only currently
      approved drug for the treatment of RSV infections in the U.S., requires high
      doses to be effective. Therefore, it has only a limited clinical efficacy in the
      treatment of RSV infections. It has been shown that a cellular ribonuclease,
      RNase L, can be recruited by 2'-5' linked tetra-adenylates (2-5A) attached to an
      antisense sequence complementary to the RSV genome to specifically cleave RSV
      genomic RNA. Here we confirm the antiviral activity of the lead 2-5A antisense
      compound, RBI034, by using several different viral assays. We demonstrate that
      RBI034 is more efficient than antisense lacking 2-5A or small interfering dsRNA
      (siRNA) in inhibiting RSV replication. Although the best antiviral activity of
      RBI034 was observed with co-treatment of RSV infection, it remained effective
      even when administered 24 h after the initiation of infection. Interestingly, the
      activity of RBI034 can be further enhanced by a combination treatment with
      ribavirin. At suboptimal concentrations, neither ribavirin nor RBI034 was
      effective in suppressing RSV replication. However, a combination of these two
      drugs at the same suboptimal concentrations showed a potent inhibitory activity.
      The potent reduction of RSV replication by combination treatment was also
      confirmed in primary human airway epithelial cells. Therefore, a combination
      therapy of the 2-5A antisense compound RBI034 and ribavirin might be a more
      effective therapeutic approach for treating RSV infections than ribavirin alone.

PMID- 15168802
TI  - Chemokine mRNA levels in mononucleated cells of HIV-infected patients before and
      after initiation of PI- versus NNRTI-containing HAART.
AB  - To compare CC chemokine mRNA levels from native peripheral blood mononucleated
      cells (PBMCs) before and 6 months after the initiation of two different regimens
      of highly active antiretroviral therapy (HAART), we treated group 1 (n = 11) with
      two nucleoside analogues and the protease inhibitor (PI) indinavir boosted by
      ritonavir (800/100 mg b.i.d.); group 2 (n = 8) was treated with the non
      nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz instead of PI. CC
      chemokine mRNA levels (regulated upon T cell activation expressed secreted
      [RANTES], macrophage inhibitory protein [MIP]-1alpha, MIP-1beta, monocyte
      chemotactic protein [MCP]-1, MCP-2) were quantified from PBMCs before and 6
      months after the initiation of HAART using a reverse transcription/real-time
      polymerase chain reaction (PCR) assay. The mRNA levels of MCP-1 and MCP-2 were
      significantly decreased in both groups (P < 0.05), while MIP-1alpha and MIP-1beta
      were decreased significantly only in the PI-treated group, but not in the NNRTI
      group. A moderate decrease of RANTES was observed in both treatment groups. The
      data suggest that HAART regimens containing either NNRTI or PI are not equivalent
      with regard to modification of CC chemokine mRNA profiles.

PMID- 15168803
TI  - Gadolinium-enhanced magnetic resonance imaging: a useful radiological tool in
      diagnosing pediatric IBD.
AB  - BACKGROUND: Recent advances in gadolinium-enhanced magnetic resonance imaging (G
      MRI) have been developed to enhance the resolution of the intestinal mucosa and
      facilitate the differentiation of ulcerative colitis (UC) from Crohn's disease
      (CD). The objective of this study is to apply this technology in Pediatrics.
      METHODS: A G-MRI was performed on 58 consecutive children with suspected IBD
      between 1999 and 2002 using intravenous gadolinium, fat suppression, and
      respiration-suspended sequences to enhance the resolution of the intestinal wall.
      The sensitivity and specificity in diagnosing either UC or CD was determined by
      comparing the G-MRI to the established histologic diagnosis. RESULTS: G-MRI
      confirmed the diagnosis of either CD (21) or UC (7) with a sensitivity and
      specificity of 96% and 92%, respectively. Among the 21 patients with CD, 14
      showed proximal small bowel involvement by G-MRI. In total, 17 patients were
      diagnosed with indeterminate colitis (IC) based on histologic criteria alone, and
      among these patients, G-MRI had a significantly lower non-classification rate (P
      < 0.02). In comparison, endoscopy was less sensitive (57%), but more specific
      (100%) than either histology or G-MRI in diagnosing IBD. G-MRI also showed a
      strong concordance with computed tomography in diagnosing CD (P = 0.001).
      CONCLUSION: G-MRI is a both a sensitive and specific radiologic tool in
      diagnosing pediatric IBD. In patients with CD, G-MRI may be useful in identifying
      proximal small bowel involvement. Longitudinal follow-up studies are needed in
      those patients diagnosed with IC to determine the predictive value of G-MRI
      testing.

PMID- 15168804
TI  - Long-term outcome of treatment with intravenous cyclosporin in patients with
      severe ulcerative colitis.
AB  - OBJECTIVES: Iv cyclosporin A (CSA) is an effective therapy in patients with
      severe ulcerative colitis (UC). It remains unclear if this treatment affects the
      course of the disease in the long run. We investigated the long-term efficacy and
      safety in 86 patients with ulcerative colitis treated with i.v. CSA at our
      center. METHODS: The records of all patients treated with i.v. CSA between
      11/1992 and 11/2000 were reviewed. RESULTS: Seventy-two of 86 patients (83.7%)
      responded to i.v. CSA therapy, administered for a mean of 9 +/- 2 days. Following
      the initial treatment, 69 patients (96%) were discharged on oral CSA with mean
      blood CSA concentrations of 192 +/- 55 ng/mL. Azathioprine was added in 64 (89%)
      patients. A second treatment with CSA was necessary in 11 patients; 1 patient
      received three courses of i.v. treatment. The duration of follow-up averaged 773
      +/- 369 days. Patients who were responders but were still having certain symptoms
      at discharge had a higher incidence of colectomy during follow-up. Of all initial
      responders, 18 (25%) underwent colectomy after a mean interval of 178 +/- 141
      days. The life-table predicts that of all treated patients, 55% will avoid a
      colectomy during a period of 3 years. Complications of CSA treatment were mostly
      reversible, but 3 patients (3.5%) died of opportunistic infections (1 of
      Pneumocystis carinii pneumonia and 2 of Aspergillus fumigatus pneumoniae). One
      patient with anaphylactic shock caused by the CSA solvent was successfully
      resuscitated. CONCLUSIONS: CSA is an effective treatment of the majority of
      patients with severe attacks of UC, although the toxicity and even mortality
      associated with its use necessitates careful evaluation, selection, and follow
      up.

PMID- 15168805
TI  - 6-Mercaptopurine is effective in Crohn's disease without concomitant steroids.
AB  - BACKGROUND: 6-Mercaptopurine (6-MP) has shown efficacy in the treatment of
      Crohn's disease when used in conjunction with corticosteroids. Sparse literature
      to date suggests that 6-MP is effective when used without steroids. We therefore
      studied the efficacy of 6-MP in corticosteroid-naive Crohn's patients. METHODS:
      We conducted a retrospective chart review of 24 patients who were treated with 6
      MP but had never received any form of steroid treatment at any time. 6-MP
      efficacy was assessed with serial modified Harvey-Bradshaw scores. In addition to
      overall response, data were also analyzed according to the indication for
      treating with 6-MP (disease activity, fistulae, or both). The time to relapse and
      the treatments required were also analyzed. RESULTS: Overall, remission or
      significant improvement was seen in 20 patients (83% of original group). Seven
      patients (29%) achieved complete remission; another 13 patients (54%)
      demonstrated significant clinical improvement. By indication, 89% of patients
      treated for activity, 50% of patients treated for activity and fistula, and 100%
      of patients treated for fistula alone showed response. Drug effect required a
      median of 5.7 months to occur (for all patients: range, 1.7-37.9 months).
      Thirteen of the twenty patients who improved or remitted on 6-MP eventually
      relapsed, usually due to stopping 6-MP, at a median of 13.8 months (range, 0.9
      57.8). Relapse was less frequent if patients continued 6-MP. Treatment of
      relapses required only antibiotics, and/or restarting 6-MP (or increasing the
      dose) in most patients. CONCLUSIONS: 6-MP is an effective medication for use in
      steroid-naive patients and is likely to be effective in patients who have
      received steroids in the past but are not currently receiving them. Relapses
      occur despite continued therapy, but are often easily treated, and do not require
      initiating steroids.

PMID- 15168806
TI  - Epstein-Barr virus viral load in Crohn's disease: effect of immunosuppressive
      therapy.
AB  - BACKGROUND: More than 80% of non-Hodgkin lymphomas (NHLs) occurring in transplant
      recipients on immunosuppressive therapy are associated with Epstein-Barr virus
      (EBV) infection. EBV viral load (EBV-VL) is predictive of NHL occurrence in this
      setting. The aim of this work was to determine EBV-VL in patients with Crohn's
      disease (CD), both according to disease activity and use of immunosuppressive
      therapy, including infliximab. METHODS: Between December 1999 and July 2001, EBV
      VL was determined 212 times by quantitative polymerase chain reaction (PCR) assay
      in 138 patients with CD and in 24 EBV-seropositive controls free of CD. RESULTS:
      EBV-VL did not differ significantly between the controls and the patients with CD
      and was not influenced by CD activity or by immunosuppressive therapy, including
      recent infliximab infusion. High EBV-VL values were observed in two patients with
      severe uncontrolled CD, but returned to normal once the flare-up had been
      controlled (by immunosuppressive drugs in one case and by surgery in the other
      case). CONCLUSIONS: EBV viral load is on the whole similar in patients with
      Crohn's disease and in EBV-seropositive controls. Infliximab infusion does not
      seem to increase significantly EBV-VL in the short-term. However, some patients
      with Crohn's disease have transient, very high EBV-VL values that are compatible
      with an increased risk of NHL in the transplant setting. The long-term clinical
      outcome of these patients must be determined.

PMID- 15168807
TI  - Perianal fistulae following infliximab treatment: clinical and endosonographic
      outcome.
AB  - BACKGROUND: Management of perianal and rectovaginal fistulae complicating Crohn's
      disease (CD) is unsatisfactory. Infliximab is effective in the treatment of
      fistulating CD. However, reopening of fistulae is frequent, suggesting the
      persistence of deep fistula tracts despite superficial healing. In this study,
      the clinical and endosonographic behavior of perianal fistulae were evaluated
      following infliximab infusions, as well as the role of anal endosonography (AE)
      in predicting their outcome. METHODS: Thirty CD patients presenting with perianal
      and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5
      mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical
      assessments were repeated at same intervals and at week 10. AE was performed at
      entry and at week 10. Thereafter, the perianal region was re-examined every 6
      months, and patients were investigated regarding draining of the fistula in the
      previous months. RESULTS: Fifteen patients (53.6%) showed closure of the fistulae
      at week 10, but only 5 patients had the fistula tracts disappeared at AE.
      Clinical and AE closure of rectovaginal fistulae was less prevalent than that of
      perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1%
      at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of
      fistulae was not affected by their number and AE classification, presence of
      rectal disease, or setons. Twenty patients with perianal fistulae were followed
      for a median of 15.5 months. Patients with closed perianal fistulae at week 10
      and disappearance of fistulae tract at AE showed a lower relapse rate than those
      with endosonographic persistence of fistula tract. CONCLUSIONS: Infliximab can
      heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients,
      respectively. Despite closure, most fistula tracts are still detectable at AE.
      Persistence of the internal tract is a condition at higher risk of fistula
      recurrence.

PMID- 15168808
TI  - Immune sensitization to yeast antigens in ASCA-positive patients with Crohn's
      disease.
AB  - BACKGROUND: Alimentary antigens may play a role in the perpetuation of
      inflammation in Crohn's disease (CD). Yeast antigens are widespread components of
      food. A proportion of CD patients develop antibodies against the yeast
      Saccharomyces cerevisiae (ASCA), but little is known about the cellular immune
      reactivity against food antigens in antibody-positive and -negative patients.
      METHODS: Lymphocytes from patients with CD, ulcerative colitis, and healthy
      controls were tested for their proliferative response after stimulation with the
      yeast antigen mannan and ovalbumin. The cellular phenotypes and activation
      markers were analyzed via FACS. Cytokine concentrations and antibody titers were
      determined by ELISA. RESULTS: Only lymphocytes of ASCA-positive patients with CD
      proliferated after stimulation with mannan. These lymphocytes expressed increased
      activation markers (CD25, CD69). Activation of T cells was mediated by antigen
      presenting cells and was associated with increased tumor necrosis factor-alpha
      (TNF-alpha) levels. The immune reactivity to ovalbumin was predominantly found in
      CD patients. It was weaker compared with mannan, independent of ASCA status, and
      also present in healthy controls. CONCLUSIONS: A disturbed humoral and cellular
      response to the yeast antigen mannan is specifically seen in a subgroup of CD
      patients. This phenomenon may be due to a loss of tolerance toward yeast and is
      possibly genetically determined.

PMID- 15168809
TI  - Basic epidemiology of inflammatory bowel disease in Puerto Rico.
AB  - BACKGROUND: Previous epidemiological studies have suggested that the incidence of
      inflammatory bowel disease (IBD) is lower in Latin American populations. The aim
      of this study was to estimate the incidence of IBD in Puerto Rico, a
      predominantly Hispanic population. METHODS: A nonconcurrent prospective study was
      conducted in collaboration with private gastroenterologists in southwest Puerto
      Rico. Basic medical history and demographics were extracted from the medical
      records of patients for which a new diagnosis of IBD (Crohn's disease, CD;
      ulcerative colitis, UC; or nonspecified IBD) was made during each of the years
      1996-2000. RESULTS: A total of 202 eligible cases of IBD were identified (95
      male, 107 female). Forty-eight patients were diagnosed with CD, 102 with UC, and
      52 with nonspecified IBD. The total incidence of IBD increased significantly
      between 1996 and 2000 (3.07/100,000 to 7.74/100,000; p < 0.001), being
      significantly higher for CD (four-fold increase, p < 0.01) and nonspecified IBD
      (fourfold increase, p < 0.005), but not UC (1.7-fold increase). The prevalence of
      CD was higher in males with an earlier age of onset (p < 0.05). CONCLUSIONS: This
      study demonstrates that the incidence of IBD within the Puerto Rican population
      is increasing and may be higher than previously reported for other Latin American
      populations.

PMID- 15168810
TI  - The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic
      acid-induced colitis in rats: an experimental study.
AB  - The limited efficacy of standard medical therapies for inflammatory bowel
      diseases has resulted in a continuing search for alternative treatments. Growth
      hormone (GH) has shown to have mutagenic and proliferative effects on intestinal
      cells. This study was designed to identify the effect of growth hormone on
      trinitrobenzene slfonic acid-induced colitis (TNBSIC) in rats. This study was
      carried out on 30 rats, divided in 3 groups: group 1: TNBSIC+ GH, group 2:
      TNBSIC, group 3: saline enema. Colitis was induced in male Sprague-Dawley rats
      (200 g-250 g) by intracolonic installation of 2, 4, 6-trinitrobenzene sulphonic
      acid in 50% ethanol. GH treatment has been started and continued throughout the
      study after inducing colitis. All rats were killed after 5 weeks and colonic
      segments were examined histopathologically. Microscopic and macroscopic damage
      scores were caulculated. Intestinal damage scores were found higher in Goups II
      when compared with treatment group (P < 0.05). There was no damage in group 3 as
      expected. Both macroscopic and microscopic scores were highest in group 2 (P <
      0.05). The myloperoxidase activity was found lower comparing to group 2 (P <
      0.05). In conclusion, growth hormone replacement had protective effects against
      colonic inflammation while reducing intestinal damage on TNB-induced colitis.

PMID- 15168811
TI  - CARD15 mutation analysis in an Italian population: Leu1007fsinsC but neither
      Arg702Trp nor Gly908Arg mutations are associated with Crohn's disease.
AB  - BACKGROUND: CARD15 gene mutations have been demonstrated to confer a high risk of
      Crohn's disease (CD). Despite this, recent studies reported variable associations
      between CD and CARD15 mutations in distinct ethnic groups, thus raising the
      hypothesis that genetic and/or allelic heterogeneity may influence the
      relationship between CARD15 and CD. The purpose of this study was to evaluate the
      frequency of the main mutations of the CARD15 gene (Leu 1007fsinsC, Arg702Trp,
      and Gly908Arg) in Italian CD patients and to establish possible genotype
      phenotype correlations. METHODS: One hundred sixty-five CD patients and 125
      healthy subjects were consecutively enrolled from January to November 2001. The
      Leu1007fsinsC mutation was assessed by denaturing high-performance liquid
      chromatography and Arg702Trp and Gly908Arg mutations by Pyrosequencing
      technology. RESULTS: Among the CARD15 gene mutations tested, only the
      Leu1007fsinsC was associated with CD (30/165 CD patients, 18%, versus 3/125
      healthy subjects, 2.4%; p < 0.001). In particular, 23 CD patients were
      heterozygotes and 7 were homozygotes. No healthy subject exhibited the mutant
      homozygous genotype. Odds ratios for CD were 6.9 for heterozygotes and 41.0 for
      homozygotes. The genotype-phenotype analysis revealed that a fibrostenosing CD of
      the distal ileum was more frequent in patients carrying the Leu1007fsinsC
      mutation. CONCLUSIONS: This study confirms the association between CARD15 gene
      mutations and CD and shows that only the Leu1007fsinsC mutation is a risk factor
      of CD in an Italian population.

PMID- 15168812
TI  - Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM
      1.
AB  - BACKGROUND: Leukocyte recruitment to areas of inflammation depends on Integrin
      VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and
      the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the
      inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM
      is mediated by a nuclear factor kappaB (NF-kappaB)-dependent mechanism. We
      investigated whether the anti-inflammatory properties of butyrate are mediated
      via the modulation of VCAM and ICAM on human endothelial cells. METHODS: VCAM-1
      and ICAM-1 expression on human endothelial cells upon tumor necrosis factor-alpha
      (TNF-alpha) stimulation was assessd by FACS analysis. A monocyte adhesion assay
      was performed to evaluate the relevance of a modulated CAM-expression.
      Electrophoretic mobility shift assays were applied to investigate NF-kappaB
      activation. RESULTS: The observed butyrate-associated inhibition of monocyte
      adhesion to endothelial cells is associated with an inhibition of NF-kappaB
      activation in human endothelial cells. In this context, the observed suppression
      of the TNF-alpha induced VCAM-1 expression is likely to play an essential role.
      CONCLUSIONS: Butyrate inhibits VCAM-1 mediated leukocyte adhesion to human
      endothelial cells. This inhibition may contribute to the anti-inflammatory
      effects of butyrate in patients with distal ulcerative colitis.

PMID- 15168813
TI  - Pulmonary involvement in Crohn's disease report of a case and review of the
      literature.
AB  - Crohn's disease (CD) is a granulomatous systemic disorder of unknown etiology.
      Obvious pulmonary involvement is exceptional in patients with CD. We report a
      case of a 38-year-old man who suffered from CD for more than 14 years and was
      treated with oral steroids for more than 10 years. Surgical excision of parts of
      the ileum was performed for life-threatening ileal bleeding caused by CD. After
      acute tapering of oral steroids, pulmonary symptoms and radiologic abnormalities
      were noted. Lung biopsy through thoracoscopy was performed and revealed signs of
      chronic inflammation with multiple subepithelial noncaseating and epithelioid
      granulomas on pathologic examination. Intravenous steroids were required in the
      initial management of life-threatening pulmonary dysfunction after diagnostic
      thoracoscopy and led to marked improvement. Tuberculocidal therapy was performed
      until all microbiological cultures were negative. Oral steroid dosage had slowly
      been tapered over 1 month. He was discharged with clinical and radiologic
      improvements. After 36 months, the patient's condition is stable on continued
      treatment with prednisolone and mesalazine.

PMID- 15168814
TI  - Ocular manifestations of inflammatory bowel disease.
AB  - Extraintestinal manifestations of inflammatory bowel disease (IBD) occur in one
      third of patients. Ocular complications are infrequent, occurring in less than
      10% of cases, but can be associated with significant morbidity, including
      blindness. Ocular complaints are often nonspecific; clinical relevance may not be
      appreciated by patient or physician and, thus, be misdiagnosed. Evaluation of the
      eye should be a routine component in the care of patients with IBD. Clinicians
      must be aware of the spectrum of ocular symptoms and know that these complaints
      may precede a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We
      review ocular pathology in IBD to alert clinicians to the diverse, at times
      confusing, spectrum of eye disorders associated with these diseases. Clinical
      manifestations include blurred vision, teary, burning or itchy eyes, ocular pain,
      photophobia, conjunctival or scleral hyperemia, loss of visual acuity, and
      possible blindness. Many patients are unaware that IBD has a risk of eye
      complications and, therefore, patient education is vital.

PMID- 15168815
TI  - Rare extraintestinal manifestations of inflammatory bowel disease.

PMID- 15168816
TI  - Pharmacogenetics and inflammatory bowel disease: progress and prospects.

PMID- 15168817
TI  - Molecular aspects of intestinal epithelial cell-bacterial interactions that
      determine the development of intestinal inflammation.
AB  - The mechanisms by which intestinal epithelial cells perceive and respond to
      microbes, both pathogenic and commensal, is important to understand the
      pathogenesis of inflammatory diseases. Recent work has established that most
      eukaryotic cells possess families of receptors that can detect the structural
      signatures of prokaryotic life. Cells respond to the detection of microbes by
      activation of distinct cytoplasmic signaling cascades that ultimately result in
      the transcriptional activation of programs of genes with proinflammatory and anti
      apoptotic function. These responses generally suffice to eliminate microbial
      threats. Also important are potential mechanisms by which microbes can influence
      the intestinal epithelial responses, influences with significant implications for
      the normal function of the intestine and inflammatory diseases.

PMID- 15168818
TI  - BMP-7: a new TGF-beta family member takes the stage in colitis treatment.

PMID- 15168819
TI  - Intravenous cyclosporine in severe ulcerative colitis: how low can you go?

PMID- 15168820
TI  - The elusive causes of relapse in ulcerative colitis.

PMID- 15168822
TI  - Genomics and proteomics: implications for inflammatory bowel diseases.

PMID- 15168821
TI  - Giving the NOD to a new understanding of Crohn's disease: mother nature has
      finally started to show her CARDs.

PMID- 15168823
TI  - New endoscopic tools for the IBD physician.

PMID- 15168824
TI  - Genetic origin of IBD.

PMID- 15168825
TI  - Host-flora interactions in inflammatory bowel disease.

PMID- 15168826
TI  - Gene disruption and immunity in experimental colitis.

PMID- 15168827
TI  - Mucosal immunity in Crohn's disease.

PMID- 15168828
TI  - The epidemiology of IBD: a lot of data but little knowledge. How shall we
      proceed?

PMID- 15168829
TI  - Pharmacogenomics and IBD: TPMT and thiopurines.

PMID- 15168830
TI  - Mechanisms of infliximab: the reverse side of a drug effect.

PMID- 15168832
TI  - Therapeutic modulation of signal transduction pathways.

PMID- 15168831
TI  - Novel biological strategies in inflammatory bowel diseases.

PMID- 15168833
TI  - Innate immunity and apoptosis in IBD.

PMID- 15168835
TI  - Reaching a balance between privacy, privilege and planning: a look at barriers to
      obtaining information for patients with criminal involvement.
AB  - Persons with serious and persistent mental disorders present unique problems for
      the criminal justice system. The challenges are tremendous as courts venture into
      problem solving models, attempting to integrate mental health services with the
      criminal justice system. Gathering and accessing confidential information is
      often difficult. This article will identify and explore the legal issues related
      to obtaining such information.

PMID- 15168834
TI  - Mentally ill persons in the criminal justice system: some perspectives.
AB  - There is an increasing number of severely mentally ill persons in the criminal
      justice system. This article first discusses the criminalization of persons with
      severe mental illness and its causes, the role of the police and mental health,
      and the treatment of mentally ill offenders and its difficulties. The authors
      then offer recommendations to reduce criminalization by increased coordination
      between police and mental health professionals, to increase mental health
      training for police officers, to enhance mental health services after arrest, and
      to develop more and better community treatment of mentally ill offenders. The
      necessary components of such treatment are having a treatment philosophy of both
      theory and practice; having clear goals of treatment; establishing a close
      liaison between treatment staff and the justice system; understanding the need
      for structure; having a focus on managing violence; and appreciating the crucial
      role of case management, appropriate living arrangements, and the role of family
      members.

PMID- 15168836
TI  - Bridging healthcare, police, and court responses to intimate partner violence
      perpetrated by individuals with severe and persistent mental illness.
AB  - A subgroup of individuals with severe and presistent mental illness (SPMI) commit
      acts of intimate partner violence (IPV). State and federal legislators have
      enacted statutes altering police response to IPV. Proarrest laws have curbed
      police discretion to a degree, and resulted in more IPV arrests. Unaware of
      alternative options, such as family court, mental health professionals may refer
      families with IPV to the police. However, perpetrators with SPMI may be
      inappropriate for adjudication in the criminal justice system. A singular legal
      response to IPV may miss the opportunity for detection and assertive treatment of
      SPMI, that could promote safety and reduce the likelihood of violence. Offenders
      with SPMI may also have difficulty comprehending court procedures. This article
      discusses the potential for a more flexible approach to IPV through
      interdisciplinary coordination and training of police, judges, attorneys, legal
      advocates, mental health professionals and substance abuse providers.

PMID- 15168837
TI  - Persons with severe mental disorders in the criminal justice system: challenges
      and opportunities.
AB  - Persons with schizophrenia and other severe mental disorders are at risk for
      falling through the cracks between the criminal justice and mental health
      systems. This article is based on a panel discussion between representatives from
      both systems that recently convened at a regional conference to discuss
      integration of services. The purpose of the panel discussion was to identify
      challenges and opportunities related to integrating mental health and criminal
      justice services at each phase of the criminal justice process. A synopsis of the
      discussion is presented, along with new models of service delivery designed to
      prevent the inappropriate arrest and incarceration of persons with severe mental
      disorders.

PMID- 15168838
TI  - Continuity and intensity of care among women receiving outpatient care for PTSD.
AB  - Continuity of care (COC) is often used as an indicator of treatment quality for
      patients with severe psychiatric or addictive disorders. However, few studies
      have examined the relationship between measures of COC and treatment outcomes.
      This study used standard regression models to examine the strength of the
      association between continuity of care measures and health outcomes for a sample
      of female veterans newly entering outpatient treatment for PTSD. There were few
      consistently significant associations between COC and outcome measures. Four
      months following program entry only one measure of treatment process, commitment
      to treatment, was positively associated with one or more continuity of care
      measures and several COC measures were associated with poor outcomes. Eight
      months following program entry patients with greater COC during the first four
      months of treatment had greater declines in violent behavior and PTSD
      measurements and larger increases in global functioning. However, when a
      Bonferonni corrected alpha of P < .001 was used to adjust for multiple
      comparisons, none of the relationships remained statistically significant. Thus,
      this study provides only weak and inconsistent evidence of the clinical benefits
      of continuity of care.

PMID- 15168839
TI  - Mixed versus manic bipolar disorder: a comparison of demographic, symptomatic,
      and treatment differences.
AB  - This study compared patients diagnosed with Mixed versus Manic Bipolar disorder
      across the domains of demographic, symptom, and treatment variables. The sample
      included 152 patients who were admitted to an acute care psychiatric facility
      within an index period, whose discharge diagnosis was either Bipolar Disorder,
      Manic Episode (n = 109) or Bipolar Disorder, Mixed Episode (n = 43). No
      significant differences were found in age, race, episode number, or length of
      stay. There was a trend toward females being diagnosed with a Mixed Episode and
      males a Manic Episode. Group differences were found on physician and nurse
      symptom ratings, with the manic group receiving higher ratings on resistance,
      psychosis, and conceptual disorganization and the mixed receiving higher scores
      on depression and anxiety. On self-report measures, the mixed group endorsed
      greater severity than did the manic group. The mixed group was more likely to be
      prescribed antidepressants at discharge; however there were no significant
      differences across other medication. These differences are discussed.

PMID- 15168841
TI  - The occurrence of cyanide formation in six full-scale publicly owned treatment
      works.
AB  - This paper presents results from an intensive monitoring program implemented at
      six full-scale publicly owned treatment works (POTWs) to investigate the fate and
      formation of cyanide in wastewater treatment processes, with a focus on
      chlorination and dechlorination processes. A review of historical monitoring data
      for cyanide species in these POTWs was also conducted. This POTW monitoring
      program provided a database for the investigation of cyanide formation in
      wastewater secondary treatment. Data from participating POTWs showed evidence of
      cyanide formation in this 1-year monitoring effort, although the cyanide
      formation pattern varied significantly from one plant to another and among
      seasons. Generally, the chlorination of thiocyanate (SCN-) seems to be the most
      important mechanism for the formation of cyanide in wastewater treatment
      processes, especially in chlorination and dechlorination. This hypothesis is
      supported by the findings of a related laboratory study of mechanisms of cyanide
      formation in POTWs. It is recommended that POTWs monitor SCN in influent and
      secondary effluent to identify its presence and adjust chlorine dose
      appropriately.

PMID- 15168842
TI  - Formation of free cyanide and cyanogen chloride from chloramination of publicly
      owned treatment works secondary effluent: laboratory study with model compounds.
AB  - The potential generation of cyanide species in wastewater upon chlorination in
      the presence of residual ammonia (resulting in chloramine formation) was
      investigated in experiments with synthetic solutions and publicly owned treatment
      works (POTW) secondary effluent. This study demonstrated that low concentrations
      (approximately 5 to 25 microg/L as cyanide) of cyanogen chloride (CNCI), a highly
      toxic cyanide species not measured in total or free cyanide analyses, could be
      detected as a result of chloramination reactions in POTW secondary effluent. The
      potential for chloramination of nitrogen-bearing organic compounds to yield CNCl
      and/or free cyanide was demonstrated in experiments with synthetic solutions
      spiked with selected precursor organics: L-serine, benzene, catechin, and humic
      acid. The amino acid L-serine yielded the largest concentrations of CNCI upon
      chloramination. Additionally, detectable cyanide (approximately 10 microg/L) was
      observed in solutions of L-serine and in POTW secondary effluent that was
      chloraminated followed by dechlorination to prevent destruction of any free
      cyanide produced. Thus, chlorination of POTW secondary effluent containing
      residual ammonia can lead to chloramination of organic compounds and the
      resulting production of CNCl and free cyanide.

PMID- 15168843
TI  - Water-extractable phosphorus in biosolids: implications for land-based recycling.
AB  - Phosphorus-based nutrient management will inevitably be required for land
      application of biosolids. Water-extractable phosphorus (WEP) in livestock manures
      is an indicator of phosphorus loss from agricultural watersheds and this study
      evaluated its use for biosolids. The WEP to total phosphorus percentage (PWEP) in
      41 biosolids (representing a variety of wastewater and solids treatment
      processes) was compared to dairy and poultry manures and triple superphosphate
      fertilizer. The mean PWEP for conventionally treated and stabilized biosolids was
      2.4%, which was significantly lower than inorganic fertilizer (85%), dairy manure
      (52%), and poultry manure (21%). Low biosolids PWEP is attributed to elevated
      aluminum and iron content from chemical additions during wastewater treatment and
      solids dewatering operations. Facilities using biological phosphorus removal had
      the highest mean biosolids PWEP (approximately 14%), whereas heat-dried biosolids
      had the lowest average PWEP (< approximately 0.5%). Paired samples of digested
      cake and the corresponding biosolids treated by processes to further reduce
      pathogens (i.e., thermal treatment, composting, and advanced alkaline
      stabilization) showed that these processes tended to reduce biosolids PWEP.
      Biosolids composition and processing mode exert a controlling influence on the
      potential for off-site phosphorus migration at land-application sites. Nutrient
      management policies for land-based recycling should account for the widely
      varying potential of organic amendments to cause soluble phosphorus losses in
      runoff and leaching.

PMID- 15168844
TI  - Characteristics of biotic and abiotic removals of dissolved organic carbon in
      wastewater effluents using soil batch reactors.
AB  - Biodegradable dissolved organic carbon (BDOC) analyses and abiotic adsorption of
      dissolved organic carbon (DOC) from different wastewater effluent were conducted
      to evaluate biotic and abiotic removal mechanisms as a function of the initial
      DOC concentration and source of DOC using soil batch reactors. To obtain high DOC
      concentrations, a laboratory-scale reverse osmosis unit was used. It was found
      that BDOC fraction was independent of the initial DOC concentration and was
      dependent on the source of wastewater and/or the types of wastewater treatment.
      The BDOC fractions varied from 9 to 73%. Trickling filter effluent (Tucson,
      Arizona) showed the highest BDOC, ranging from 65 to 73% biodegradable, while
      wastewater treated by the soil aquifer treatment (SAT) (NW-4) was found to be
      most refractory, with DOC removals of 9 to 14%. For nitrified/denitrified
      tertiary effluent (Mesa, Arizona) and secondary effluent (Scottsdale, Arizona),
      36 to 42% removal of DOC was observed during the BDOC test. The amount of BDOC in
      the wastewater depended not on the concentration of DOC, but on the effectiveness
      of pretreatment. Abiotic adsorption capacity of wastewater effluent varied from 6
      to 18%. Molecular weight distribution analyses showed that more than 50% of DOC
      in the Scottsdale concentrate had a molecular weight of less than 1000 Da, and no
      significant change in distribution profiles occurred after approximately 12%
      abiotic adsorption with both soils with acclimated microorganisms (SAT soil) and
      soils without acclimated microorganisms (non-SAT soils). Hence, preferential
      adsorption was not observed and the presence of acclimated microbes did not
      influence adsorption.

PMID- 15168845
TI  - Phase distribution of hexachlorobenzene in a suspended-growth culture amended
      with a polysorbate surfactant.
AB  - The effect of a non-ionic surfactant on the phase distribution of
      hexachlorobenzene (HCB) in a suspended-growth culture system was assessed. Tween
      60, a polyoxyethylene sorbitan stearate ester surfactant, and an azide
      inactivated, mixed, methanogenic, HCB-dechlorinating culture were used in this
      work. The sorption of HCB on the biomass as well as sorption and
      aggregation/precipitation of Tween 60 were experimentally quantified. The values
      of the HCB and Tween 60 distribution parameters were determined and the phase
      distribution of HCB in the presence of surfactant and biomass was described
      quantitatively. Both the HCB and surfactant distribution are highly dependent on
      the total amount of surfactant present in the system. At low initial surfactant
      concentrations, most of the HCB is associated with the biomass. As the surfactant
      concentration increases, the effect of surfactant sorption and precipitation
      diminishes and the higher pool of surfactant micelles shifts the distribution of
      HCB from the solid phase to the solution phase. The HCB phase distribution in the
      presence of the surfactant may have a significant effect on HCB bioavailability
      for reductive dechlorination. The quantitative description of the HCB phase
      distribution presented here was subsequently used as the basis for the
      development of a model that describes the bioavailability and reductive
      dechlorination of HCB in a surfactant/biomass system.

PMID- 15168846
TI  - The effect of residual chemical oxygen demand on anoxic and aerobic phosphate
      uptake and release with various intracellular polymer levels.
AB  - This study investigated the anoxic and aerobic phosphate uptake and release
      reactions and the fraction of denitrifying phosphate-accumulating organisms
      (DPAOs) under various initial chemical oxygen demand (COD) and residual COD
      conditions. The results showed that DPAOs and non-DPAOs could release phosphate
      when high soluble COD was present. Consequently, the phosphate-uptake potential
      was dynamic and increased when the initial COD increased, the initial
      polyhydroxyalkanoates (PHA) increased, and the residual COD decreased.
      Furthermore, the electron acceptor (oxygen of nitrate) has more significant
      influence on the phosphate uptake/release characteristics, while the residual COD
      concentrations have little influence on that. The fraction of DPAOs to phosphate
      accumulating organisms was 42% when the initial PHA storage was enough by both
      DPAOs and non-DPAOs. This was closely related to the relative phosphate uptake
      (47%) in the anoxic zone of the process.

PMID- 15168847
TI  - Influence of chemical oxygen demand/total Kjeldahl nitrogen ratio and sludge age
      on nitrification of nitrogenous wastewater.
AB  - Four laboratory-scale biological nitrification units (influent total Kjeldahl
      nitrogen [TKN] = 1002 to 1062 mg/L) were operated at chemical oxygen demand
      (COD)/TKN ratios of approximately 0.5, 1.0,15, and 2.0 and at three different
      sludge ages of 30, 20, and 10 days to study the influence of COD/TKN, sludge age,
      COD loading, and TKN loading on nitrification and nitrifiers. Percent
      nitrification was found to increase with decreases in COD/TKN and increases in
      sludge age. The average nitrifier concentration increased from 460 mg/L at a
      COD/TKN of 2.22 and a sludge age of 10 days to 706 mg/L at a COD/TKN of 0.676 and
      a sludge age of 30 days. The nitrifier fraction was found to be higher at a lower
      COD/TKN and lower at a higher COD/TKN. The nitrifier fraction increased with the
      decrease in sludge age and COD loadings and the increase in TKN loadings. The
      effect of sludge age on the nitrifier fraction was amplified at a COD/ TKN of
      approximately 0.5 rather than at approximately 2.0. The nitrification rate
      (kilograms TKN oxidized per kilograms nitrifiers per day) was shown to be
      dependent on COD/TKN and sludge age. The activity performed by Nitrobacter was
      affected at all COD/TKN ratios studied as well as at a sludge age of 10 days.
      This was manifested by the accumulation of high levels of nitrite-nitrogen in the
      nitrified effluent. The presence of heterotrophs did not affect nitrification
      rates and the growth of nitrifiers, which were found to be beneficial. High
      sludge age and COD loadings resulted in a higher sludge volume index of more than
      200 mL/g mixed liquor suspended solids. Microscopic examination showed
      filamentous structure of sludge under these conditions. It is concluded from the
      investigations that a sludge age of 30 days and a COD/TKN of approximately 1.0
      are optimal to yield maximum nitrification and nitrifier growth rates for
      treating high-strength nitrogenous wastewater.

PMID- 15168848
TI  - Ozone disintegration of excess biomass and application to nitrogen removal.
AB  - A pilot-scale facility integrated with an ozonation unit was built to investigate
      the feasibility of using ozone-disintegration byproducts of wasted biomass as a
      carbon source for denitrification. Ozonation of biomass resulted in mass
      reduction by mineralization as well as by ozone-disintegrated biosolids
      recycling. Approximately 50% of wasted solids were recovered as available organic
      matter (ozonolysate), which included nonsettleable microparticles and soluble
      fractions. Microparticles were observed in abundance at relatively low levels of
      ozone doses, while soluble fractions became dominant at higher levels of ozone
      doses in ozone-disintegrated organics. Batch denitrification experiments showed
      that the ozonolysate could be used as a carbon source with a maximum
      denitrification rate of 3.66 mg nitrogen (N)/g volatile suspended solids (VSS) x
      h. Ozonolysate was also proven to enhance total nitrogen removal efficiency in
      the pilot-scale treatment facility. An optimal chemical oxygen demand (COD)-to
      nitrogen ratio for complete denitrification was estimated as 5.13 g COD/g N. The
      nitrogen-removal performance of the modified intermittently decanted extended
      aeration process dependent on an external carbon supply could be described as a
      function of solids retention time.

PMID- 15168849
TI  - Residence time distribution model for soil filters.
AB  - Pulse tracer tests were carried out to determine the residence time distribution
      (RTD) in earthworm-cultured and uncultured, laboratory-scale soil filters. A two
      parallel-cell dispersion model for the mixing behavior in soil filters is
      presented; the model showed excellent fit to experimental data. Results showed a
      fitted Peclet number of 0.83 to 0.89 for the uncultured soil filter and 0.18 to
      0.29 for the cultured soil filter. Results also determined that the cultured soil
      filter dispersion number (1/Pe) was relatively high, showing the significant
      effect of earthworms on mixing. Reactor performance data and dispersion model
      predictions based on present RTD model parameters also reveal good agreement,
      indicating the usefulness of RTD parameters for describing real situations.

PMID- 15168850
TI  - Determination of the required surface area of a final clarifier for an activated
      sludge system.
AB  - A generic methodology for determining the required surface area of a final
      clarifier is presented. Clarification and thickening requirements are integrated
      to form a unified procedure for final clarifier design. The new method is based
      on results obtained by Yuen (2002) on the solids flux theory for a secondary
      clarifier; it does not require the specification of recycle rate, which is
      computed as an output of the method. The author shows that there is a minimum
      required surface area (A(m)) for a final clarifier under the thickening
      requirement when the designed recycle rate is set at the maximum allowable value
      (FR)m (at the critical state). The designed surface area and the return activated
      sludge pumping capacity can be determined by applying a safety factor to A(m) and
      (FR)m, respectively. The method is shown to conform to conventional design
      criteria under typical design conditions.

PMID- 15168851
TI  - Comparison of oxygen-transfer measurement methods under process conditions.
AB  - The objective of this paper is to compare the following four methods of measuring
      oxygen transfer in wastewater treatment plants under process conditions: the
      offgas, hydrogen peroxide (H2O2), reaeration, and in situ oxygen uptake rate
      (OUR) methods. Comparative tests were performed under controlled conditions in a
      pilot column and in six full-scale oxidation ditches equipped with fine-bubble
      diffusers and slow-speed mixers. The offgas and H2O2 methods give similar results
      (differences between the oxygen-transfer coefficients under field conditions
      [k(L)a(f)] from each method lower than 10%). The reaeration procedure gives more
      random results (differences from -5 to -43% compared with values obtained using
      the offgas method). The in situ OUR method, in the presence of a horizontal flow
      of mixed liquor, leads to an estimate of k(L)a(f) to within 15% of the offgas
      value.

PMID- 15168852
TI  - Solasodine glycoside production by hairy root cultures of Physalis minima Linn.
AB  - Hairy root cultures of Physalis minima L. were developed using Agrobacterium
      rhizogenes, strain ATCC 15834 mediated transformation and grown in half strength
      of Murashige and Skoog medium containing 8% (w/v) sucrose. Media supplementation
      with 1 mg naphthalenacetic acid l(-1) and 1 mg benzyladenine increased solasodine
      glycoside up to 900 g dry wt, which was 20 times higher than that in the native
      root.

PMID- 15168853
TI  - A study into the anti-microbial properties of an amino functionalised polymer
      using multi-parameter flow cytometry.
AB  - Fluorescent staining techniques were used to study the anti-microbial properties
      of aqueous suspensions of a novel, water insoluble amino functionalised polymer
      on three micro-organisms Pseudomonas fluorescens, Staphylococcus epidermidis and
      Saccharomyses cerevisiae. The mechanism of action was similar for each organism
      in that, after various contact times with the polymer, a progressive change in
      individual cell physiological state was measured using multi-parameter flow
      cytometry. The microbiocidal activity of this polymer may be similar to that of
      substances referred to as polycationic, amphipathic compounds (peptides, peptide
      derivatives and other polyamines).

PMID- 15168855
TI  - Hydrolysis of rice bran oil using an immobilized lipase from Candida rugosa in
      isooctane.
AB  - The kinetics of enzymatic hydrolysis of rice bran oil in isooctane by immobilized
      Candida rugosa lipase in a batch reactor showed competitive inhibition by
      isooctane with a dissociation constant, K1, of 0.92 M. Continuous hydrolysis of
      rice bran oil was performed in recycling, packed bed reactor with 4352 U of
      immobilized lipase; the optimum recycle ratio was 9 and the operational half-life
      was 360 h without isooctane but 288 h with 25% (v/v) isooctane in rice bran oil.

PMID- 15168854
TI  - Adaptive responses to static conditions in nutrient-rich cultures of luminous
      Ralstonia eutropha.
AB  - The lux-gene fused Ralstonia eutropha, when adapting to static conditions, causes
      stratification of air-exposed and nutrient-rich cultures at above 0.15 mg biomass
      ml(-1). The O2 respiring biofilm (luminous neuston) phase, along with the dark
      sub-neustonic suspension phase, develops within 5-60 min. The instability of the
      biphasic static culture was identified as a reason for occasionally observable
      oscillatory bioluminescence.

PMID- 15168856
TI  - Selective antimicrobial activity of chitosan on beer spoilage bacteria and
      brewing yeasts.
AB  - Chitosan (0.1 g l(-1)), assayed in a simple medium, reduced the viability of four
      lactic acid bacteria isolated during the beer production process by 5 logarithmic
      cycles, whereas activity against seven commercial brewing yeasts required up to 1
      g chitosan l(-1). Antimicrobial activity was inversely affected by the pH of the
      assay medium. In brewery wort, chitosan (0.1 g l(-1)) selectively inhibited
      bacterial growth without altering yeast viability or fermenting performance.

PMID- 15168857
TI  - Functional identification of the gene locus (ncg12319 and characterization of
      catechol 1,2-dioxygenase in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum assimilated phenol, benzoate, 4-hydroxybenzoate p
      cresol and 3,4-dihydroxybenzoate. Ring cleavage was by catechol 1,2-dioxygenase
      when phenol or benzoate was used and by protocatechuate 3,4-dioxygenase when the
      others were used as substrate. The locus ncg12319 of its genome was cloned and
      expressed in Escherichia coli. Enzyme assays showed that ncg12319 encodes a
      catechol 1,2-dioxygenase. This catechol 1,2-dioxygenase was purified and accepted
      catechol, 3-, or 4-methylcatechols, but not chlorinated catechols, as substrates.
      The optimal temperature and pH for catechol cleavage catalyzed by the enzyme were
      30 degrees C and 9, respectively, and the Km and Vmax were determined to be 4.24
      micromol l(-1) and 3.7 micromol l(-1) min(-1) mg(-1) protein, respectively.

PMID- 15168858
TI  - Degradation of carbazole in the presence of non-aqueous phase liquids by
      Pseudomonas sp.
AB  - Biodegradation of carbazole was enhanced by the presence of a non-aqueous phase
      liquid (logKo/w > or = 3.1) at phase ratio of 1:1 (organic/aqueous). In a
      cyclohexane/aqueous phase system, the maximum specific degradation rate (3.34 mg
      carbazole min(-1) g dry cell(-1)) was at an organic/aqueous ratio of 1:1.
      Pseudomonas sp. XLDN4-9 degraded 47% (w/w) of 1 g carbazole l(-1) in cyclohexane
      phase directly within 1 h.

PMID- 15168859
TI  - SEREX identification of the autoantibodies that are prevalent in the
      cerebrospinal fluid of patients with moyamoya disease.
AB  - We performed SEREX (serological analysis of recombinant cDNA expression library)
      to identify autoantibodies that are prevalent in the cerebrospinal fluid of
      patients with moyamoya disease. These autoantibodies include PC326 (of unknown
      function), SRY (sex determining region Y), and peroxisomal D3,D2-enoyl-CoA
      isomerase.

PMID- 15168860
TI  - Cloning and characterization of a sigma 70 homologue gene, sigA from
      Corynebacterium ammoniagenes.
AB  - A sigma 70-like gene, sigA, has been identified from Corynebacterium
      ammoniagenes. The sigA gene encodes a polypeptide of 467 amino acids with a
      calculated molecular mass of 52036 Da. The deduced amino acid sequence preserves
      the common motifs of the primary sigma factors and shows very high similarity to
      those of SigA (sigmaA) homologues from high G+C Gram-positive bacteria, which
      suggest that the sigA gene encodes the primary sigma factor. The sigA gene is
      transcribed as a monocistronic mRNA of 2 kb and its mRNA occurs during the
      exponential growth phase and decays rapidly on entry into the stationary phase.
      The open reading frame encoding polyphosphate glucokinase-like protein is closely
      linked to the sigA gene.

PMID- 15168861
TI  - The impact of dnaKJ overexpression on recombinant protein solubility results from
      antagonistic effects on the control of protein quality.
AB  - We have produced increasing levels of DnaK and its co-chaperone DnaJ along with
      the model VP1LAC misfolding-prone protein, to explore the role of DnaK on the
      management of Escherichia coli inclusion bodies. While relative solubility of
      VP1LAC is progressively enhanced, the heat-shock response is down-regulated as
      revealed by decreasing levels of GroEL. This is accompanied by an increasing
      yield of VP1LAC and a non-regular evolution of its insoluble fraction, at
      moderate levels of DnaK resulting in more abundant inclusion bodies. Also, the
      impact of chaperone co-expression is much more pronounced in wild type cells than
      in a DnaK- mutant, probably due to the different background of heat shock
      proteins in these cells. The involvement of DnaK in the supervision of misfolding
      proteins is then pictured as a dynamic balance between its immediate holding and
      folding activities, and the side-effect downregulation of the heat shock response
      though the limitation of other chaperone and proteases activities.

PMID- 15168862
TI  - Evaluation of cellulose-binding domain fused to a lipase for the lipase
      immobilization.
AB  - A cellulose-binding domain (CBD) fragment of a cellulase gene of Trichoderma
      hazianum was fused to a lipase gene of Bacillus stearothermophilus L1 to make a
      gene cluster for CBD-BSL lipase. The specific activity of CBD-BSL lipase for oil
      hydrolysis increased by 33% after being immobilized on Avicel (microcrystalline
      cellulose), whereas those of CBD-BSL lipase and BSL lipase decreased by 16% and
      54%, respectively, after being immobilized on silica gel. Although the loss of
      activity of an enzyme immobilized by adsorption has been reported previously, the
      loss of activity of the CBD-BSL lipase immobilized on Avicel was less than 3%
      after 12 h due to the irreversible binding of CBD to Avicel.

PMID- 15168863
TI  - Hydroxylation of 10-deoxoartemisinin to 15-hydroxy-10-deoxoartemisinin by
      Aspergillus niger.
AB  - The microbial hydroxylation of 10-deoxoartemisinin was investigated with the aim
      of obtaining preparative yields of hydroxy derivatives. During 14 d at 28 degrees
      C and pH 6.5 Aspergillus niger transformed 10-deoxoartemisinin (500 mg l(-1)) to
      15-hydroxy-10-deoxoartemisinin (26%) and 7beta-hydroxy-10-deoxoartemisinin (69%).

PMID- 15168864
TI  - Polymer-coated liposomes resistant to enzymatic hydrolysis.
AB  - A polymerizable electrolyte, 2-aminoethyl 1,6-heptadien-4-yl phosphate (AEHDP),
      which has the same hydrophilic head group as naturally occurring phospholipids,
      was prepared. Five equivalents of AEHDP were added to a suspension of liposomes
      (closed bilayer vesicles made of phospholipids) and layered on the liposomes.
      After polymerization by UV irradiation, the resulting polymer-coated liposomes
      were resistant to hydrolysis of their constituent phospholipids by phospholipase
      A2.

PMID- 15168865
TI  - Study of the dermatophytes in dogs and the risk of human infection.
AB  - BACKGROUND: The infiltrative growth of fungi that multiplies in the tissues
      (dermatophytes, candida, agents of visceral mycoses) is the generally known proof
      of "active" functioning of these organisms. The relative importance of fungi as
      inducers of human and animal diseases grows constantly. METHODS: The study was
      carried out on dogs that showed skin changes. The frequency of examinations was
      determined on the basis of anamneses. Skin scrapings and affected fragile or dull
      hair and skin swabs were subject to Laboratory diagnostic examinations based on
      cultivation and microscopical examination. Our evaluations were focused on the
      type of parasite--ecothrix, endothrix, neoendothrix, and the size of
      arthrospores. RESULTS: The results of our study are presented as the incidence of
      dermatophytes and other micromycetes in 100 samples of skin scrapings and swabs
      from 100 dogs of both sexes, different breeds and age categories that had
      exhibited skin problems. We isolated 12 species. Malassezia pachydermatis was the
      most frequently detected species and was isolated from 31 cases. Trichophyton
      mentagrophytes was isolated from 2 samples, species Microsporum canis was
      isolated only from one case, Candida albicans was isolated from 3 samples. The
      agent Candida krusei was isolated from 5 samples, Candida pulcherrima a
      relatively rare candidal species, was isolated from skin of an 8-year old
      Dalmatian bitch, Candida sp. in 5 cases. Trichosporon cutaneum was isolated from
      a 3-year old Laika etc. CONCLUSION: This study confirms the need of constant
      research in this area. This indicates that the incidence of mycoses in dogs and
      other pets is of importance in the exposure of people to the risk of acquiring
      mycotic infections. (Tab. 1, Fig. 5, Ref. 57).

PMID- 15168866
TI  - Effects of dietary extra virgin olive oil on serum lipid resistance to oxidation
      and fatty acid composition in elderly lipidemic patients.
AB  - An inverse relation between high consumption of olive oil and low incidence of
      coronary heart disease among the people living in Mediterranean countries has
      been proposed. It has been shown, that an oleic acid-rich diet could increase the
      resistance of human LDL to in vitro oxidation which is postulated to play an
      important role in the development of atherosclerotic lesions. The aim of this
      study was to assess the effect of extra virgin olive oil consumptiom on the
      resistance of serum lipids to in vitro oxidation and on fatty acid composition in
      the serum of elderly lipidemic patients. A total of 26 patients (mean age 69
      years) with combined hyperlipidemia consumed daily 2 table spoons (approx. 20 g)
      of extra virgin olive oil for 6 weeks. Plasma lipids, total antioxidant capacity,
      indices of serum lipid oxidizability (lag time and maximal rate of oxidation) and
      the content of fatty acids in serum phospholipids were determined before and
      after dietary supplementation with olive oil. Plasma total cholesterol and LDL
      cholesterol decreased significantly after 6 weeks of dietary intervention. A
      significant increase in the lag time of conjugated diene formation (p = 0.026)
      and the decrease in the rate of lipid oxidation (p = 0.030) were observed after
      olive oil consumption. The changes in the fatty acid profile were characterized
      by an increase in oleic acid content (p = 0.005) as well as by a decline in the
      content of linoleic acid (p = 0.020) and arachidonic acid (p = 0.022). Linear
      regression analysis revealed some interesting and significant correlations
      between indices of serum lipid resistance to oxidation and individual fatty
      acids, suggesting a protective effects of olive oil in lipoprotein oxidation. In
      conclusion, the daily consumption of extra virgin olive oil in elderly lipidemic
      patients favourably affected serum lipoprotein spectrum and fatty acid
      composition that probably contributed to the increased resistance of serum lipids
      to oxidation. (Tab. 2, Ref. 18).

PMID- 15168867
TI  - Antiasthmatic effects of nedocromil sodium.
AB  - Accumulating data indicate that bronchial asthma is a chronic inflammatory
      disease. Airway inflammation and it's control became a principal focus in asthma
      treatment. Nedocromil sodium is chemically nonsteroidal anti-inflammatory agent
      for the treatment of mild to moderate asthma. The aim of the study was to
      determine the effects of NS on bronchial hyperresponsivness and eosinophil
      activation markers isolated from peripheral blood of asthmatics with mild
      intermittent asthma. Twenty nine patients of both sexes (17 women, 12 men) with
      average age of 34 years were recruited into the clinical open study. Bronchial
      responsivness was assessed by metacholine challenge test prior to starting
      therapy with NS (preparation Tilade mint aer) and 3rd week and 9th week of follow
      up. Baseline lung function tests were performed at intervals before treatment and
      at 3rd and 9th week, respectively. Eosinophil activation markers were determined
      before and after 3rd and 6th week. Assessement was done by flow cytometry using
      standard monoclonal antibodies. Bronchial responsivness decreased significantly
      at 3rd and 9th week of follow up (provocation dose--PD20 increased significantly,
      p < 0.05, p < 0.02, respectively). Improvements of baseline lung function tests
      were observed in majority of parameters: FVC (p < 0.01), FEV1 (p < 0.01),
      FEV1/FVC (p < 0.01), MEF 25 (p < 0.03), MEF 50 (p < 0.01), MEF 25-75 (p < 0.01),
      PEF (p < 0.01) after 3rd week, however the enhancement of improvement was seen in
      majority of parameters after 9th week of the study. Significant reduction of
      eosinophil activation markers expression was noticed: CD69 (p < 0.05, p < 0.01)
      and HLA DR (p < 0.05, p < 0.05) after 3rd and 6th week, respectively and CD66 (p
      < 0.05) after 3rd week and CD81 (p < 0.05) after 6th week of follow up. NS
      possessed complex antiasthmatic effects resulting in decrease of bronchial
      responsivness and reduction of eosinophil activation markers in mild asthmatics.
      The tolerance of the drug was good and no adverse effects have been reported. NS
      is effective prophylactic drug recommended for use in both adults and children in
      long-term management of mild asthma. (Tab. 2, Fig. 1, Ref. 27).

PMID- 15168868
TI  - Plasma lipid parameters in patients with alcoholic fatty liver after treatment
      with essential phospholipids.
AB  - BACKGROUND: Fatty liver is the earliest and most common response to alcohol. The
      accumulation of lipid particles in hepatocytes alters the ultrastructure of
      cellular membranes. The purpose of our study was to investigate the effect of the
      administration of essential phospholipids on plasma lipid parameters in patients
      with alcoholic fatty liver. METHODS: Our open clinical trial was performed in
      patients suffering from alcoholic fatty liver. The investigated group consisted
      of 29 patients. Two capsules of Essentiale forte were administered 3 times daily
      for 3 months. Individual biochemical parameters were examined each month. Values
      of total cholesterol, HDL- and LDL-cholesterol, triacylglycerols, apoprotein A
      and B were determined. RESULTS: The therapy with essential phospholipids had
      positive effects on the parameters of hepatocyte integrity. The levels of total
      cholesterol, triacylglycerols and apoprotein B were significantly higher in
      patients with fatty liver than in the controls. The concentration of HDL
      cholesterol was also higher before the therapy than in the control group. There
      was no difference in levels of apoprotein A and LDL-cholesterol between the
      patients and the controls. There was no significant therapeutic effect on plasma
      lipid parameters in the group of patients with fatty liver. CONCLUSIONS: The
      effects of treatment of alcoholic fatty liver with essential phospholipids were
      studied. The therapy had positive effects on the parameters of hepatocyte
      integrity. There was no significant therapeutic effect of the therapy on plasma
      lipid parameters. (Tab. 2, Fig. 1, Ref. 20).

PMID- 15168869
TI  - Influenza vaccination--knowledge, attitudes, coverage--can they be improved?
AB  - The reasons for low rate of influenza vaccination in Slovakia have been analyzed
      in selected target groups. In our questionnaire study we focused on the level of
      knowledge about this vaccination and the attitudes towards it. We selected three
      target groups: medical students, nurses and printing company workers. The authors
      as well tried to identify the ways how the flu vaccination coverage could be
      increased in the future. The questionnaire survey revealed several surprising
      facts. Though almost all the respondents knew about the existence of influenza
      vaccine, less than one quarter of them have ever received influenza shot. Despite
      our expectations that the main source of information about influenza prevention
      in medical students and nurses would be from their medical and nursing studies,
      it was shown to be from mass media instead. Even more staggering was the distrust
      towards the vaccination as a reason for not being vaccinated in a high proportion
      of both the medical students and the nurses. The majority of medical students
      would not even want to get a vaccination, even if it were to be provided for
      free. These results suggest that if we want to improve the low influenza
      vaccination coverage within the general population of our country, we will have
      to focus our attention primarily on the professional groups of medical workers
      and medical and nursing students who should be able to provide the public with
      the competent advice. Therefore, changing the current negative approach and
      improving the deficit in knowledge concerning vaccination are the key tasks for
      all under- as well as postgraduate teachers of medicine and nursing in Slovakia,
      especially, but not exclusively, of those specialised in public health.(Tab. 3,
      Fig. 2, Ref. 8).

PMID- 15168870
TI  - "No-reflow" phenomenon as a cause of hypoperfusion after severe head injury?
AB  - INTRODUCTION: Severe head injuries are known to cause secondary ischaemic brain
      damage. Ischaemia may develop due to transtentorial herniation or due to
      increased intracranial pressure leading to decreased perfusion. Compression of
      the brain due to extracerebral haematoma may cause hypoperfusion as well.
      METHODS: 29 patients with postraumatic transtentorial herniation were studied.
      Haematoma was urgently removed in these patients and CT and SPECT was performed
      on the 1st and 5th postoperative day. 26 patients had hypoperfusion on SPECT in
      the vicinity of the previous haematoma. Only 9 of them, however, had ischaemia on
      CT. There were 11 patients in whom the previous ischaemia seen on SPECT improved
      on the follow up SPECT examination. 10 of them had a good treatment result.
      CONCLUSION: A possible mechanism of hypoperfusion caused by compression of the
      brain may be a kind of "no-reflow" phenomenon which is known from pathophysiology
      of classical brain ischaemia. Patients in whom the collateral blood flow
      overcomes the decreased perfusion in the microcirculation should have a better
      outcome. (Tab. 1, Fig. 1, Ref. 13).

PMID- 15168871
TI  - Tracheostomy in critically ill patients.
AB  - The authors made a retrospective analysis of results and complications of
      elective tracheostomies performed by percutaneous dilatational technique (PDT) as
      well as standard surgical procedure (ST) in critically ill patients in the ICU.
      The indication for tracheostomy was to facilitate long-term mechanical
      ventilation, to facilitate cleaning and management of the airway and to maintain
      upper airway patency. During a 5-year period there were 495 elective
      tracheostomies performed in the ICU setting, in 209 females and 286 males. From
      these, 408 were standard (82.4%) and 87 percutaneous dilatational tracheostomies
      (17.6%). Mean age of patients with tracheostomy was 63.3 years (range 17-93
      years) and the mean duration of endotracheal intubation before tracheostomy was 7
      days (range from 13 minutes to 21 days). During the monitored period 144 patients
      (29.0%) were decannulated, out of which 34 patients (23.6%) had PDT and 110
      patients (76.4%) ST. A total of 265 patients (53.5%) with tracheostomy died and
      86 patients (17.3%) had the tracheostomy cannule in place at the study
      conclusion. Perioperative complications totaled 14 (2.8%), the most serious being
      one cardiac arrest and death (0.4%) both in ST as well as in PDT groups. Early
      postoperative complications totaled 46 (9.2%). Late postoperative complications
      totaled 7 (1.4%). Percutaneous dilatational tracheostomy is an alternative method
      to standard surgical tracheostomy in critically ill patients in the ICUs.
      Standard surgical tracheostomy is an irreplaceable procedure in patients with
      complex anatomic condition or in high-risk patients. (Tab. 3, Ref. 11).

PMID- 15168872
TI  - Anaesthesia management of major hepatic resections without application of
      allogeneic blood.
AB  - BACKGROUND: In a prospective study we used acute normovolemic haemodilution (ANH)
      together with low CVP anaesthesia in order to avoid allogeneic blood transfusion
      during major liver surgery. MATERIAL AND METHODS: With institutional approval, 20
      patients, ASA classification I-III, undergoing hepatic lobe resection
      consecutively (18 for metastatic cancer, 2 for hepatocellular cancer) in 2002,
      were enrolled into the prospective study. A epidural catheter was inserted before
      surgery in the thoracic region. General anaesthesia was induced and maintained
      with sevoflurane and fentanyl. Invasive haemodynamic monitoring was instituted.
      Blood was removed for ANH and circulation volume was replaced by infusion of
      colloids and crystalloid. The CVP was maintained less than 5 mm Hg during hepatic
      parenchymal transection. After procedure the ventilated patients were transported
      to ICU. RESULTS: The preoperative haematocrit value (Hct) allowed performance of
      ANH with a blood removal (1025 +/- 357 g) in all patients. The estimated blood
      loss was 825 +/- 515 ml. None of the subject received allogeneic blood during
      surgery. One patient had transfusion of 2 units of allogeneic blood the fifth day
      after the right hepatectomy during a second look for perihepatic hematoma. The
      CVP was 3.8 +/- 0.4 mmHg during liver resection. Postoperative Hct was 0.31 +/-
      0.02 and haemoglobin 108 +/- 11 g/L. All patients were extubated the first day
      after surgery. There was no hospital mortality. CONCLUSIONS: We have shown that
      the routine use of new surgical techniques and low CVP anaesthesia in combination
      with ANH enabled avoidance of allogeneic blood transfusion in all patients during
      surgery. (Tab. 3, Ref. 22).

PMID- 15168873
TI  - Polymorphous low grade adenocarcinoma of the parotid gland. Cytological,
      histological and immunohistochemical features and review of the literature.
AB  - AIM: Polymorphous low grade adenocarcinoma of the salivary glands (PLGA) is a low
      grade neoplasm that predominantly occurs in the minor salivary glands. In this
      site is amenable to biopsy and histologic diagnosis. However, experience with
      cytological findings in these tumors is limited. We describe the cytology of this
      entity. EXPERIMENTAL DESIGN: Touch imprint cytology of a primary parotid PLGA is
      specified and correlated with histology. RESULTS: Smears were hypercellular
      showing branching papillae, sheets and clusters of uniform cells with bland
      nuclei, dispersed chromatin and no nucleoli. The cells had a scant to moderate
      amount of eosinophilic cytoplasm. They formed tubular structures containing
      hyaline globules. CONCLUSIONS: The cytologic differential diagnosis of PLGA
      includes adenoid cystic carcinoma, pleomorphic adenoma, and monomorphic adenoma.
      PLGA should be considered in the differential diagnosis of head and neck tumors,
      where the cytology suggests on of the above mentioned tumors, even when the
      clinical findings (involvement of a major salivary gland, lymph node metastasis)
      is not typical of PLGA.

PMID- 15168874
TI  - Effect of nimodipine on histological alterations in basilar artery following the
      bilateral common carotid artery ligation (preliminary study).
AB  - BACKGROUND: The blood supply to tissues is reduced as a result of arterial
      occlusions. Angiogenesis, collateral circulation and reverse flow mechanisms go
      into operation to restore a continued adequate supply of blood. Ca++ channels
      undertake the major part of this function. As a result of the increasing tension
      on the arterial walls, vascular autonomy is affected, and ischemia and even
      necrosis are observed. METHOD: Adult 100 male hybrid rabbits were used in this
      study. The bilateral carotid arteries were ligated at the carotid bifurcation.
      The rabbits were divided into 2 main groups: treatment and control, and then both
      groups were further divided into 5 subgroups consisting of 10 rabbits each. The
      rabbits were sacrificed between the first day and the end of 8 weeks for
      histopathological examination of the basilar artery in two groups. RESULTS: In
      control groups, after 24 hours of the occlusion partial swelling and minor
      endothelial damage were observed in histopathological sections of the basilar
      artery. Luminal flattening started to decrease, and expanding of the diameter
      continued. The increase in the diameters of the basilar artery was higher in
      animals treated by nimodipine, and that difference was statistically significant
      (P=0,000). CONCLUSION: This study revealed that the intimal and medial
      alterations arising from the increased blood flow rate in the basilar artery
      might be lessened and even partially prevented by the use of nimodipine.

PMID- 15168875
TI  - Anticholinergic drugs--functional antidotes for the treatment of tabun
      intoxication.
AB  - 1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats
      were injected intramuscularly with organophosphate tabun (LD50). The efficacy of
      choice antidotal treatment consisting of acetylcholinesterase reactivator
      obidoxime and one of four anticholinergic drugs (atropine, benactyzine,
      biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity
      progress was carried out using the method Functional observational battery. The
      experimental animals as well as controls were observed at 24 hours and 7 days
      following tabun or saline administration. 3. The results were compared to the
      condition of animals without anticholinergic drug (oxime alone) and control rats
      that received physiological solution instead of tabun and treatment. Antidotal
      treatment involving centrally acting anticholinergic drugs (benactyzine,
      biperiden, scopolamine) showed significantly higher neuroprotective efficacy
      compared to antidotal treatment containing atropine.

PMID- 15168877
TI  - Morphofunctional modification in elderly individuals practicing competitive
      endurance sport.
AB  - To investigate the modification of body composition and level of aerobic capacity
      in older athletes practicing competitive sport for two years consecutively, 20
      elderly male endurance athletes (A) were compared with twenty elderly male
      subjects who practiced moderate exercise (C). Body composition analysis, physical
      activity and maximal aerobic power (VO2max) were measured at the beginning of the
      study, after twelve months and after twenty-four months in both groups. We
      observed significant differences in group A: body fat was significantly lower in
      the subjects at the first and second year than at the beginning of the study; fat
      free mass (FFM) was significantly higher in the subjects at the first and second
      year; VO2max in every measurements was significantly higher in the subjects at
      the at the first and second year than at beginning of the study. Our data suggest
      that it is possible, even in the elderly, to reach a good level of physical
      fitness with appropriate training protocols for competitive sport.

PMID- 15168876
TI  - Radioprotective effects of amifostine (WR-2721) or cystamine on radiation damage
      and its repair in rats whole body exposed to fission neutrons.
AB  - Sulphur containing radioprotective drugs amifostine (gammaphos, WR-2721) or
      cystamine (disulfide of meracaptoethylamine) of Czechoslovak production were
      examined in whole body fission neutrons irradiated rats in the thermal column of
      reactor VVR-S. Using the split-dose technic the first sublethal neutron dose in
      the range 1-2 Gy was followed by second lethal exposures in the two time
      intervals (3 or 6 days) using whole body fission neutrons irradiations (3 days
      interval) or whole body gamma-irradiations (6 days interval) for LD50/30
      evaluation within next 30 days survival observation. In other experiments the
      mean survival time (MST) in days was estimated in different rats group, when
      animals were whole body fission neutrons irradiated twice with 3-days interval
      using the total lethal doses of 4 or 5 Gy. Protected rats received amifostine
      (160 mg.kg(-1) i.p. and 200 mg.kg(-1) i.m.) or cystamine (40 mg.kg(-1) i.p. and
      50 mg.kg(-1) i.m.), control rats obtained saline 20 min before beginning of
      irradiation in the amount of 0.5 ml.100 g(-1) of the rat's body weight. Non
      significant DRF value 1.13 for WR-2721 i.p. was calculated in survival studies in
      rats twice neutron irradiated with 3 days interval (DRF 1.04 for cystamine).
      Chemical protectors were administered before each neutron exposure. MST of twice
      neutron lethal iradiated rats was prolonged not regularly by radioprotectors
      tested. WR-2721 and cystamine i.m. were not able to increase 6 days reparation
      processes after sublethal 2 Gy fission neutrons whole body irradiated rats.

PMID- 15168878
TI  - Predicting factors contributing to length of stay in hospitalized chronic
      obstructive pulmonary disease (COPD) patients: the role of the emergency room.
AB  - BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (COPD) is a
      common cause of hospital admission and COPD patients usually have a long stay in
      hospital. METHODS: The objective of this study was to identify factors predicting
      length of stay in patients with exacerbation of COPD when seen in the emergency
      room. We analyzed clinical and biological variables. RESULTS: Patients with
      diminished breath sounds, systolic pressure higher than 140 mmHg, diastolic
      pressure higher than 90 mmHg and recent previous hospitalization for exacerbation
      of COPD had the longest hospital stay. CONCLUSIONS: Recognition of this clinical
      profile in the emergency room may help to increase efforts in order to diminish
      length of stay in these patients.

PMID- 15168879
TI  - Adenosine deaminase activity in the serum of type 2 diabetic patients.
AB  - Adenosine deaminase (ADA) is suggested to be an important enzyme for modulating
      the bioactivity of insulin, but its clinical significance in diabetes mellitus
      (DM) is not yet characterized. We measured the serum level of ADA in healthy
      controls (C, n=29) and type 2 diabetic patients (n=42). The mean serum level of
      ADA in C, and type 2 diabetic patients was 13.04 +/- 3.3 and was 22.2 +/- 4.3
      U/L, respectively (P<0.01[corrected] vs. C). ADA levels of patients were
      significantly correlated with HbA1c (r=0.45, p<0.01). Our findings suggest that
      ADA may play a role in insulin effect and glycamic control. On the other hand,
      increased activity of ADA in type 2 DM might be a marker for insulin indication.
      However, further studies are required for the pathogenic role of elevated ADA
      activity in type 2 DM.

PMID- 15168880
TI  - The "edge effect" after implantation of beta-emitting (55Co) stents with high
      initial activity.
AB  - The aim of this study was to evaluate the incidence and the cause of "edge
      restenosis" after implantation of high activity 41.1 microCi +/- 1.2 microCi =
      1520 kBq +/- 44 kBq, beta-emitting (55Co) stents. Proton bombarding in cyclotron
      has brought the radioactivity. Intravascular ultrasound (IVUS) investigation has
      been completed in 10 patients. The angiographies performed at 6 month revealed
      restenosis >50% in 5 cases (50%). The analysis of edges (5 mm distally and
      proximally to the last stent struts) showed no significant changes in TVV (187.3
      +/- 62.60 mm3 and 176.9 +/- 53.5 mm3) but PMV increase significantly (i.e.
      neointimal proliferation) from 61.9 +/- 31.2 mm3 to 82.2 +/- 43.4 mm3 (p<0.04)
      and was the major contributor (from 66%) to lumen volume loss (125.4 +/- 40.7 mm3
      and 94.7 +/- 22.2 mm3, p<0.02). In conclusion, neither statistically significant
      positive nor negative remodelling at the "stent edges", were present.
      Statistically significant increase in plaque +/- media volume (i.e. neointimal
      hyperplasia) and reduction in lumen volume were found. The cause of "edge
      restenosis" was especially (from 66%) due to increase in plaque +/- media volume
      (i.e. neointimal hyperplasia). Probably, main reason for "edge effect"/neointimal
      hyperplasia was in this trial sharp fall-off in radiation at the edges of the
      stents.

PMID- 15168881
TI  - Cytologic differential diagnostic problems in ulcerative cervicitis.
AB  - OBJECTIVE: To improve the detection rates in the determination of signs
      consistent with ulcerative cervicitis against signs of intraepithelial neoplasia,
      in PAP smears. STUDY DESIGN: We investigated the frequency of establishing a
      diagnosis of a simple ulcerative cervicitis by histology in a cohort of 58
      females with cervical cytology suggestive of intraepithelial neoplasia. RESULTS:
      There was found a detection rate of 81.58% in the determination of ulcerative
      cervicitis by cytology and a rate of 100% in the determination of HPV-infection,
      CIN1, CIN2 and CIN3 respectively. There was no statistically significant
      difference between cytology and histology in the diagnosis of ultracerative
      cervicitis (p>0.5, chi-square). CONCLUSIONS: There is an overestimation of the
      cytological signs in the diagnosis of ulcerative cervicitis 18.42%). There is
      also an excellent agreement in the diagnosis of HPV-infection and CIN grades
      (100%) between cytology and histology, discordant with the literature (2.4%-71%).

PMID- 15168882
TI  - Influence of discoplasty and discectomy of the temporomandibular joint on
      elimination of pain and restricted mouth opening.
AB  - The retrospective study was based on 36 open joint surgeries done in 33
      consecutive patients with anterior disc dislocation without reduction with severe
      signs and symptoms and unsuccessful nonsurgical treatment lasting at least 6
      months. The patients underwent either discoplasty or discectomy followed by
      auricular cartilage graft implantation and were evaluated for amount of
      interincisal mouth opening, severity of pain on VAS scores preoperatively and as
      well as 12 months postsurgically. The minimum pain levels were preoperatively 50
      on VAS for the discoplasty group and 60 on VAS for the discectomy group. After
      the surgery, the VAS values lower than 20 were reported on 69.4% of 25 sides
      (72.7% in the discoplasty group, 68.0% in the discectomy group). Using the cutoff
      point for maximal interincisal opening of more than 35 mm, only 6 patients
      (16.6%) fulfilled the criterion at the baseline. Interincisal distance measured
      vertically 12 months after the operation increased in all but five patients. In
      three of the five subjects, the opening was at the same level as before the
      surgery. Almost ninety-one percent of the patients (90.9%) in discoplasty group
      and 81.8% in discectomy group, respectively reached 35 mm or more of vertical
      opening after the operation. Applying the 1984 Criteria for classification of
      postoperative results (AAOMS), 12 months after surgery, 24 patients (72.7%)
      displayed good results, 6 patients (18.2%) were evaluated with acceptable
      results, and in 3 cases (9.1%) we observed bad results. Although only short-term
      evaluation is presented, our findings show that both discoplasty and discectomy
      are effective methods for surgical treatment of patients suffering from severe
      temporomandibular pain and limited mouth opening. Discoplasty should be reserved
      only for patients without severe changes of the disc.

PMID- 15168883
TI  - An atypic herpes encephalitis with Wallenberg's lateral medullary syndrome and CD
      receptors deficiency.
AB  - Herpes simplex encephalitis is a rare complication of Herpes virus infections.
      Innate immune mechanisms are the first line of defence encountered by invading
      infectious agents. A 41-year-old man was admitted to the neurology department
      with the complaints of fever, headache, vertigo, tinnitus and ataxia. His first
      brain Magnetic Resonance Imagine showed nodular lesions in the medulla oblongata
      and the second showed a new left occipital lobe lesion in addition. In sera,
      Herpes Simplex Virus IgG and M values were positive and liver enzymes were found
      to be elevated. His diagnosis was Herpes encephalitis with liver involvement.
      CD19, CD20, CD21, CD22, CD35 receptors were found to be diminished. In this case
      we want to address that one of the causes of Wallenberg's lateral medullary
      syndrome can be Herpes simplex virus-1 and probable immune system deficiency can
      be researched.

PMID- 15168884
TI  - What are appropriate initial and salvage therapies for patients with thrombotic
      thrombocyopenic purpura (TTP)?
AB  - Although much has been learned about the pathophysiologic process of thrombotic
      thrombocytopenic purpura (TTP), both diagnostically and therapeutically, since
      its initial description by Moschowitz in 1924, its etiology and treatments
      remain, in many instances, problematic. Thrombotic thrombocytopenic purpura
      remains a rare entity whose etiology is usually unknown, but several drugs and
      infections have now been implicated in its development. Although treatment by
      plasma exchange has gained worldwide acceptance, the optimal exchange media is
      not known, nor the volume and duration of exchange therapy, not appropriate
      salvage therapies. Without the benefit of randomized controlled trials, its
      treatment, to a large extent, remains not evidence-based but "eminence-based",
      making the same mistakes with increasing confidence over decades.

PMID- 15168886
TI  - Assessing the practice of laboratory medicine.

PMID- 15168887
TI  - Equivalent quality control.

PMID- 15168888
TI  - Neoplasm at the head of the pancreas: a case study.

PMID- 15168889
TI  - Faculty members acceptance of web-based education.
AB  - OBJECTIVE: To assess the effect of the WebCLS project on clinical laboratory
      science (CLS) faculty members including improvement of participating CLS
      educators' skills in designing, developing, delivering, and evaluating
      interactive, Web-based instructional programs. DESIGN: A survey was developed
      that included 24 statements related to respondents' perceptions of how their
      participation in the project: a) improved their course development skills, b)
      developed their evaluation skills, and c) affected them personally. Four open
      ended questions asked the respondents to comment on the project's effect on their
      traditional course development skills, plans for future usage of WebCLS-produced
      course materials, the most beneficial outcomes of their participation, any
      problems that participation in the project caused them, and any unexpected
      positive or negative outcomes that could be attributed to their participation.
      SETTING: The survey was sent to 27 individuals who had participated in the
      project. RESULTS: Twenty-four participants completed the survey for an 89%
      response rate. The mean response was 6.82 (S.D. 2.32) with sixteen respondents'
      (73%) reporting participation at the mean or above. CONCLUSION: Overall, the
      WebCLS project accomplished its objective of improving CLS educators' Web-based,
      distance education course development skills. One of the most positive outcomes
      of the project was the survey respondents' belief that their participation in the
      project expanded their contacts with colleagues in CLS education as well as with
      instructional design experts, computer programmers, and other technical support
      personnel. Furthermore, this outcome prompted several participating faculty to
      report that this enhanced collegial relationship will sustain their interest in
      curriculum development over time.

PMID- 15168890
TI  - Topography as a contextual variable in infectious disease transmission.
AB  - OBJECTIVE: This paper examines whether or not topography is a contextual variable
      that indirectly influences the transmission of infectious diseases. Age, gender,
      race/ethnicity, education level, economic status, injection drug use, and high
      risk sexual behavior are known to influence infectious diseases transmission, but
      the effects of topography are often overlooked. DESIGN: A sample of 395 drug
      users were chosen from census tracts based upon a target profile of drug use
      behavior and demographics for the city of Houston. HIV was chosen as the
      infectious disease used to test this hypothesis. SETTING: Residents of 16 census
      tracts in Houston, Texas participated in this study. RESULTS: The findings
      revealed that census tracts that were 'isolated' by topographic barriers, such as
      bayous, parks, railroad tracks, railway yards, major thoroughfares, freeways, and
      unique street grids had fewer cases of HIV than census tracks that were more
      accessible to thru-traffic. CONCLUSION: The research findings suggest that future
      research studies should consider topography as being contextually related to
      infectious disease transmission.

PMID- 15168891
TI  - Oral creatine supplements lower plasma homocysteine concentrations in humans.
AB  - OBJECTIVE: To determine if oral creatine supplements will lower the concentration
      of total plasma homocysteine (tHcy). SETTING/PARTICIPANTS: Apparently healthy
      volunteers, at least 19 years old, were recruited from the University of South
      Alabama and surrounding community. DESIGN/INTERVENTION/MAIN OUTCOME: Participants
      took multi-vitamins daily for four weeks, then were randomly divided into two
      groups. The control group (C) continued to take multi-vitamins daily for an
      additional four weeks. The experimental group (EX) took multivitamins plus an
      amount of creatine each day equal to twice their daily creatinine excretion, for
      the additional four weeks. Total plasma homocysteine concentrations were measured
      in all participants at the beginning and at the end of the second four week
      interval. RESULTS: There were no statistically significant differences between
      the two groups in age, initial tHcy, serum folate, erythrocyte folate, serum
      vitamin B12, or creatinine excretion. After four weeks of creatine supplements,
      tHcy in EX changed by an average of -0.9 micromol/L (range: -1.8 to 0.0),
      compared to an average change of +0.2 micromol/L in C (range: -0.6 to 0.9) during
      the same four weeks. The difference in the changes in tHcy between the two groups
      was statistically significant (p < 0.01). CONCLUSION: Creatine supplements may be
      an effective adjunct to vitamin supplements for lowering tHcy.

PMID- 15168892
TI  - Oral anticoagulants.

PMID- 15168893
TI  - Unfractionated heparin and other antithrombin mediated anticoagulants.
AB  - Clinical practice over the past decade has evolved to include new agents, LMWH
      and synthetic polysaccharides, that bind to and enhance the activity of
      antithrombin similar to UFH. These drugs differ from UFH since their
      anticoagulant effect consists predominantly, or entirely, of anti-Xa activity.
      More important, the new drugs have greater predictability with regard to dosing.
      In clinical studies the new agents have proven as good as or better than UFH with
      regard to efficacy and toxicity. The synthetic polysaccharide may possess the
      greatest efficacy, but possibly with increased bleeding risk. However, UFH still
      has one advantage over these agents, the ability of its anticoagulant effect to
      undergo essentially complete reversal with an available drug, protamine sulfate.
      Thus, clinical situations favoring UFH over these newer parenteral agents still
      exist.

PMID- 15168894
TI  - Direct thrombin inhibitors.

PMID- 15168895
TI  - Word category and verb--argument structure information in the dynamics of
      parsing.
AB  - One of the core issues in psycholinguistic research concerns the relationship
      between word category information and verb-argument structure (e.g. transitivity)
      information of verbs in the process of sentence parsing. In two experiments
      (visual versus auditory presentation) using event-related brain potentials
      (ERPs), we addressed this question by presenting sentences in which the critical
      word simultaneously realized both a word category and a transitivity violation.
      ERPs for sentences with both types of violation clustered with the patterns for
      sentences with a word category violation only, but were different from the
      patterns elicited by argument structure violations in isolation, since only the
      latter elicited an N400 ERP component. The finding that an argument structure
      violation evoked an N400 only if the phrase structure of the respective sentence
      was correct suggests that a successful integration of the word category
      information of a verb functionally precedes the application of its argument
      structure information.

PMID- 15168896
TI  - Have sex differences in spatial ability evolved from male competition for mating
      and female concern for survival?
AB  - Drawing on the theoretical and empirical foundations of two evolutionary models,
      we argue that, among humans and other mammals, a twofold selection process would
      parsimoniously account for sex-linked advantages in spatial contexts. In males, a
      superiority for both solving navigation-related spatial problems and
      understanding physical principles that apply to the behavior of projectiles could
      have been inherited from mating-oriented male competition involving extensive
      ranging and agonistic displays. In females, a form of superior spatial memory may
      have been shaped in relation to a costly reproduction system compelling them to
      safeguard their survival and that of their offspring by fostering low-risk
      strategies consisting of restricted navigation as well as concentration on nearby
      spatial cues. Based on the combined action of competition and survival pressures,
      we submit new predictions as to spatial sex differences in several species
      including humans.

PMID- 15168897
TI  - Macaque monkeys discriminate pitch relationships.
AB  - This study demonstrates that non-human primates can categorize the direction of
      the pitch change of tones in a sequence. Two Macaca fascicularis were trained in
      a positive-reinforcement behavioral paradigm in which they listened to sequences
      of a variable number of different acoustic items. The training of discriminating
      pitch direction was divided into three phases with increasing task complexity. In
      the first two phases, subjects learned to employ a same/different rule. In phase
      1, they discriminated acoustic items of different sound quality. Subjects had to
      respond when there was a change from repeating noise bursts to repeating click
      trains or vice versa. In phase II, acoustic items differed along one physical
      dimension only. Subjects had to respond to a change of the frequency of a
      repeating series of pure tones. In phase III, sequences consisted of three series
      of repeating tones of different frequency. Subjects were required to respond when
      the frequency of the tones changed in a downward direction and to refrain from
      responding when the frequency remained constant or increased. After several ten
      thousand trials, subjects categorized pitch direction well above chance level.
      The discrimination was performed over a 4.5-octave range of frequencies and was
      largely independent of the temporal and ordinal position of the downward pitch
      direction within the sequence. These results demonstrate that monkeys can
      recognize pitch relationships and thus that monkeys have the concept of ordinal
      relations between acoustic items.

PMID- 15168898
TI  - Do current connectionist learning models account for reading development in
      different languages?
AB  - Learning to read a relatively irregular orthography, such as English, is harder
      and takes longer than learning to read a relatively regular orthography, such as
      German. At the end of grade 1, the difference in reading performance on a simple
      set of words and nonwords is quite dramatic. Whereas children using regular
      orthographies are already close to ceiling, English children read only about 40%
      of the words and nonwords correctly. It takes almost 4 years for English children
      to come close to the reading level of their German peers. In the present study,
      we investigated to what extent recent connectionist learning models are capable
      of simulating this cross-language learning rate effect as measured by nonword
      decoding accuracy. We implemented German and English versions of two major
      connectionist reading models, Plaut et al.'s (Plaut, D. C., McClelland, J. L.,
      Seidenberg, M. S., & Patterson, K. (1996). Understanding normal and impaired word
      reading: computational principles in quasi-regular domains. Psychological Review,
      103, 56-115) parallel distributed model and Zorzi et al.'s (Zorzi, M., Houghton,
      G., & Butterworth, B. (1998a). Two routes or one in reading aloud? A
      connectionist dual-process model. Journal of Experimental Psychology: Human
      Perception and Performance, 24, 1131-1161); two-layer associative network. While
      both models predicted an overall advantage for the more regular orthography (i.e.
      German over English), they failed to predict that the difference between children
      learning to read regular versus irregular orthographies is larger earlier on.
      Further investigations showed that the two-layer network could be brought to
      simulate the cross-language learning rate effect when cross-language differences
      in teaching methods (phonics versus whole-word approach) were taken into account.
      The present work thus shows that in order to adequately capture the pattern of
      reading acquisition displayed by children, current connectionist models must not
      only be sensitive to the statistical structure of spelling-to-sound relations but
      also to the way reading is taught in different countries.

PMID- 15168899
TI  - Neural correlates of the effects of morphological family frequency and family
      size: an MEG study.
AB  - Schreuder and Baayen (Schreuder. R., & Baayen, R. H. (1997). How complex simplex
      words can be. Journal of Memory and Language 37, 118-139) report that lexical
      decision times to nouns are not sensitive to the cumulative frequency of the
      noun's morphological derivatives in its "morphological family", even though such
      a cumulative frequency effect is obtained in the domain of inflection. Under a
      decomposition view of derivational morphology, this constitutes a puzzling
      exception to the robust finding that lexical frequency is one of the major
      determinants of behavioral response latencies. If morphologically complex words
      are decomposed, each occurrence of a member of a noun's morphological family
      should add to its root-frequency. We investigated the effects of morphological
      family frequency on the magnetoencephalographic response component M350, which
      shows sensitivity to factors affecting early stages of lexical processing,
      including lexical frequency. We hypothesized that high morphological family
      frequency should have a facilitory effect on the M350, even though no such effect
      can be seen in response time, presumably due to competition among possible root
      affix combinations. Contrary to this hypothesis, we found that high family
      frequency elicits an M350 inhibition, suggesting that competition among
      morphological family members occurs at the M350. The result is significant, since
      there is evidence that competition among phonologically similar words occurs
      after, not at, the M350. Thus, our results suggest that competition within a
      morphological family precedes competition within a phonological similarity
      neighborhood.

PMID- 15168900
TI  - Where psychology meets physiology: chronic stress and premature mortality--the
      Central-Eastern European health paradox.
AB  - A substantial and still growing body of research tries to link different
      psychological models and chronic diseases, with special emphasis on
      cardiovascular disease. These efforts have established several conceptual bridges
      that connect psychological alterations and psychosocial factors to the risks,
      onset and prognosis of cardiovascular disease. However, several different models
      have been suggested. Depression and learned helplessness are two central
      psychological models that have been shown to have major explanatory power in the
      development of chronic diseases. In this respect the so called Central-Eastern
      European health paradox, that is the morbidity and mortality crisis in these
      transforming societies can be regarded as a special experimental model. In this
      review chronic stress is proposed as an integrating theory that can be applied to
      different psychological models. Chronic stress and allostatic load has been shown
      to lead to typical pathogenetic results in animal experiments. Chronic stress
      theory is applicable to the explanation of the suddenly changing patterns of
      premature mortality rates in transforming societies. Literature and the different
      models in the field of psychology, behavioural sciences, and epidemiology are
      reviewed in terms of the chronic stress theory. The applicability of these
      results are investigated for further research, clinical and policy implications.

PMID- 15168901
TI  - Development of a stereotaxic instrument for study of the bovine central nervous
      system.
AB  - We have developed a bovine stereotaxic instrument in this study to be used for
      Holstein cattle from weanling to adult age. The bovine stereotaxic instrument is
      derived from the Horsley-Clarke principle. A pair of straight ear-bars and
      orbital ridge pieces with their carriers, head clamps, AP bars are symmetrically
      arranged across the head pace. For holding the heavy heads, a hard palate and a
      mandibular support are designed to be placed on the surface of the base frame. A
      new manipulator with long working distance has also been made. For
      ventriculography, a holder inserting an X-ray film cassette is placed just next
      to the AP bar. Finally, the instrument was combined together with an oil-operated
      lift, so that it can be adjusted to a proper height. Details of this instrument
      are described in this paper.

PMID- 15168902
TI  - Increase of the hippocampal theta activity in the Morris water maze reflects
      learning rather than motor activity.
AB  - The change in the percentage of rat hippocampal high-frequency theta activity
      from being immobile and awake to swimming behaviour was calculated for three
      groups of rats, trained in either place learning, cue learning or egocentric
      learning in the Morris water maze. The place-learning-trained rats showed an
      increase in the percentage of theta activity, along with a significant reduction
      in escape latency over the last 3 days of training. No changes were observed in
      the other two groups. Because the motor activity displayed by the three groups of
      rats was similar, we suggest that the increase in the percentage of theta
      activity concomitant with place-learning training could be related to the
      processing of information by the hippocampus, rather than to the displayed motor
      activity.

PMID- 15168903
TI  - Effects of bilateral resection of facial nerves on suckling in developing rats.
AB  - The purpose of the present study is to investigate functional role of the facial
      nerve on suckling in developing rats. The bilateral resection of facial nerves on
      postnatal day 1 (P1) resulted in cell loss of facial motoneurons and complete
      facial paralysis without any whisker movement or nictitating reflex at the end of
      the postnatal 3 weeks. Although the body weight of the nerve-resected rats
      increased gradually for the postnatal 3 weeks, they weighed less than the control
      rats without nerve resection. The nerve-resected rats contained less milk (0.25
      +/- 0.02 g) than the control rats (0.35 +/- 0.02 g) in the stomach on P17. On
      P21, the body weight of the nerve-resected rats (25.33 +/- 0.32 g) was decreased
      by 28% compared to that of the control rats (35.08 +/- 0.57 g). Although their
      growth was substantially more retarded than that of the control animals, most
      (92%) of the nerve-resected pups could survive without facial nerve innervation.
      The orofacial musculature innervated by the facial nerve plays an important role
      in breastfeeding, but the present study shows that these muscles are not
      essential for the survival of neonatal rats.

PMID- 15168904
TI  - Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion
      cells: examination of neuron survival and phagocytic microglia using fluorescent
      tracers.
AB  - Retinal ganglion cells (RGCs) regenerating through peripheral nerve grafts show
      enhanced survival after further axonal injury for at least 4 weeks [Restor.
      Neurol. Neurosci. 21 (2003) 11]. Here, we examined the survival of the neurons
      and their microglial phagocytosis in dependence of the site of reaxotomy.
      Therefore, the optic nerve in adult rats was transected at different distances
      from the eye cup and replaced with an autologous piece of sciatic nerve. After 14
      days of axonal growth, the regenerated neurites were reaxotomized either within
      the remaining optic stump or within the graft and their cell bodies were
      retrogradely labeled. Reaxotomy of regenerated ganglion cells within the
      remaining optic nerve resulted in reduced (but not significant) ganglion cell
      survival and significant microglial phagocytosis in contrast to reaxotomy within
      the peripheral nerve graft. Furthermore, phagocytosis-dependent labeling using
      two different fluorescent tracers revealed that the same microglial cell can
      phagocytose further dying ganglion cells within 14 days after the first
      activation. The results suggest that the intrasciatic segments of axons receive
      some trophic support that is retrogradely transported and required to limit the
      microglial activation. The microglial capability to phagocytose dying neurons
      several fold emphasizes their function in permanent scavenging within the retina.

PMID- 15168905
TI  - Inhibitory effects of angiotensin on NMDA-induced cytotoxicity in primary
      neuronal cultures.
AB  - Primary cultures from the hypothalamus/thalamus/septum/midbrain (HTSM) region of
      1-day-old mice were used to investigate the effects of angiotensin on NMDA
      excitotoxicity. Cell viability was determined following exposure to 1-10 mM
      glutamate or 0.01-10 mM NMDA. Cells exposed to 1 mM glutamate or 1 mM NMDA for 24
      h showed a significant increase in cell death as determined by propidium iodide
      staining. HTSM cultures treated with 0.1 mM NMDA revealed both DNA laddering and
      positive staining for TUNEL, suggesting apoptosis as the primary mechanism for
      the cell death. We also determined whether angiotensin II (Ang II) modulated NMDA
      induced cell death in HTSM-cultured neurons. Cells pre-treated with 10 nM Ang II
      showed a decrease in NMDA-induced cytotoxicity, TUNEL staining and DNA laddering.
      NMDA-induced cell death was also reduced when cells were pre-treated with the AT1
      receptor antagonist losartan. In this study, we have shown that NMDA and
      glutamate induce cell death through the NMDA receptor, and that Ang II, acting
      primarily through the AT2 receptor, can attenuate this response.

PMID- 15168906
TI  - Central AII evokes a normal sodium appetite in the Fischer rat, but its low
      spontaneous sodium intake may be related to reduced excitation and increased
      inhibition in septo-preoptic AII neurons.
AB  - Fischer rats show a low or absent basal salt appetite and a reduced intake of
      salt solutions in response to peripherally administered angiotensin II (AII) when
      compared to other strains. We investigated spontaneous sodium intake, and sodium
      intake after intracerebroventricular (i.c.v.) AII and losartan, and septo
      preoptic neuronal responses to AII and losartan, in age-matched male Fischer and
      Wistar rats. Spontaneous intake of 1.8% NaCl was lower in Fischers, but i.c.v.
      injection of 10 pmol AII produced similar 2 h intakes in a 2 h test period.
      Iontophoretic application of AII and losartan onto neurons in the septo-preoptic
      continuum revealed differences between the two strains of rat. In the Fischer
      rats only 11% of the spontaneously active neurons were sensitive to locally
      applied AII compared to approximately 30% in the Wistar. Local application of
      losartan produced neuronal inhibition in Fischer rats but neuronal excitation in
      Wistars. The central AII system appears to be regulated differently in these two
      strains, and may be related to the differences in their spontaneous sodium
      intake, but not to AII aroused sodium appetite.

PMID- 15168908
TI  - Neuroprotective effect of 4-amino-1,8-napthalimide, a poly(ADP ribose) polymerase
      inhibitor in middle cerebral artery occlusion-induced focal cerebral ischemia in
      rat.
AB  - In the present study, neuroprotective effect of 4-amino-1,8-napthalimide (4-ANI),
      a poly(ADP-ribose) polymerase (PARP) inhibitor was investigated in middle
      cerebral artery occlusion (MCAo)-induced focal ischemia. Sprague-Dawley rats were
      subjected to 2 h of middle cerebral artery occlusion followed by 22 h of
      reperfusion. After 22 h of reperfusion rats were evaluated for cerebral
      infarction, neurological deficits, brain NAD levels, and in situ terminal
      deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL).
      Focal ischemia produced significant infarct volume (201 +/- 14 mm3), neurological
      scores (2 +/- 0.5) and 28 +/- 4.5% brain NAD depletion. Ischemia was associated
      with increased in TUNEL positive cells in brain sections indicating DNA
      fragmentation. 4-ANI treatment (1 and 3 mg/kg, i.p.) significantly decreased
      infarct volume to 35 +/- 7% and 70 +/- 6%, respectively. Neurological functions
      were also significantly improved at these doses. 4-ANI (3 mg/kg) completely
      reversed brain NAD depletion and significantly reduced the increase in the number
      of TUNEL positive cells. Nevertheless, 4-ANI treatment did not alter cerebral
      blood flow and blood pressure. Our study suggests 4-ANI is a potent
      neuroprotective agent in focal cerebral ischemia and its neuroprotective effects
      may be attributed to reduction of NAD depletion and DNA fragmentation.

PMID- 15168907
TI  - Characterization of nicotinic receptors inducing noradrenaline release and
      absence of nicotinic autoreceptors in human neocortex.
AB  - Presynaptic facilitatory nicotinic receptors (nAChRs) on noradrenergic axon
      terminals were studied in slices of human or rat neocortex and of rat hippocampus
      preincubated with [3H]noradrenaline ([3H]NA). During superfusion of the slices,
      stimulation by nicotinic agonists for 2 min only slightly increased [3H]NA
      outflow in the rat neocortex, but caused a tetrodotoxin-sensitive. Ca(2+)
      dependent release of [3H]NA in rat hippocampus and human neocortex. In both
      tissues a similar rank order of potency of nicotinic agonists was found:
      epibatidine >> DMPP > nicotine approximately cytisine > or = acetylcholine;
      choline was ineffective. In human neocortex, the effects of nicotine (100 microM)
      were reduced by mecamylamine, methyllycaconitine, di-hydro-beta-erythroidine (10
      microM, each) and the alpha3beta2/alpha6betax-selective alpha-conotoxin MII
      (100/200 nM). The alpha3beta4 selective alpha-conotoxin AuIB (1 microM), and the
      alpha7 selective alpha-conotoxin ImI (200 nM) as well as alpha-bungarotoxin (125
      nM) were ineffective. Glutamate receptor antagonists (300 microM AP-5, 100 microM
      DNQX) acted inhibitory, suggesting the participation of nAChRs on glutamatergic
      neurons. On the other hand, nAChR agonists were unable to evoke exocytotic
      release of [3H]acetylcholine from human and rat neocortical slices preincubated
      with [3H]choline. IN CONCLUSION: (1) alpha3beta2 and/or alpha6 containing nAChRs
      are at least partially responsible for presynaptic cholinergic facilitation of
      noradrenergic transmission in human neocortex; (2) nicotinic autoreceptors were
      not detectable in rat and human neocortex.

PMID- 15168909
TI  - Official position of the American Academy of Clinical Neuropsychology on ethical
      complaints made against clinical neuropsychologists during adversarial
      proceedings.

PMID- 15168911
TI  - Interpreting change on ImPACT following sport concussion.
AB  - The purpose of this study was to examine the psychometric characteristics of
      Version 2.0 of ImPACT (Immediate Postconcussion Assessment and Cognitive
      Testing). The focus was on the stability of the test scores and the calculation
      of reliable change confidence intervals for the test-retest difference scores. A
      sample of 56 nonconcussed adolescents and young adults completed the test battery
      on two occasions. Test-retest coefficients, reliable change difference scores,
      and confidence intervals for measurement error are provided. These reliable
      change parameters were applied to a second sample of 41 concussed amateur
      athletes who were tested preseason and within 72 hr of injury. Applying these
      confidence intervals allows more precise determinations of deterioration,
      improvement, and recovery in the initial days following concussion.

PMID- 15168910
TI  - Neuropsychological effects of 3,4-methylenedioxymethamphetamine (MDMA or ecstasy)
      in recreational users.
AB  - While neuropsychological studies on 3,4-methylenedioxymethamphetamine (MDMA or
      ecstasy) users have been emerging, results have been inconsistent, possibly due
      to methodological issues. The current study examined the performance of 22
      recreational MDMA users compared to 28 age, education, and IQ comparable normal
      control subjects on a comprehensive battery of neuropsychological tests. Results
      revealed no significant differences in cognitive functioning between the MDMA
      users and normal controls. However, greater use of MDMA was associated with
      poorer scores on several measures of nonverbal memory, and greater frequency
      users (> or = 50 times) evidenced significantly lower scores on 2 of 3 nonverbal
      memory tests compared to lesser frequency users (< 50 times). Our results suggest
      that a subgroup of MDMA patients, specifically heavy MDMA users, evidence
      declines in nonverbal (visual) memory, however, other cognitive areas appear to
      be spared.

PMID- 15168912
TI  - Utility of the neuropsychological evaluation in an acute medical hospital.
AB  - Although recent studies have demonstrated the importance of cognitive assessment
      in medical settings in general, there have been no specific studies addressing
      the utility of the neuropsychological evaluation in the acute inpatient hospital
      setting. The current study examined the use of inpatient neuropsychological
      evaluation by treating physicians in an acute medical hospital for patient care
      and discharge disposition. Participants were 100 inpatients within an urban
      medical center who received a neuropsychological evaluation. Results showed 78%
      of hospital discharge summaries included information regarding the
      neuropsychological evaluation, 48% referenced specific results, and 68% reported
      specific recommendations. Further, actual placement outcomes were consistent with
      the neuropsychological evaluation placement recommendations 80% of the time. The
      current study supports the utility of neuropsychological evaluations on overall
      inpatient care, and discusses ways in which the results may be used to
      communicate the value of neuropsychological services to medical treatment and
      discharge planning teams, third party payors, and medical center administrators.

PMID- 15168913
TI  - Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part
      I: Validation with nongeriatric patients.
AB  - The Behavioral Dyscontrol Scale is a measure of executive abilities initially
      designed to predict functional independence in geriatric populations. The current
      study examined the utility of two Behavioral Dyscontrol Scale (BDS) scoring
      systems in a nongeriatric sample. The BDS was administered to 49 TBI patients
      undergoing inpatient and outpatient rehabilitation. The results demonstrate
      slightly greater utility of the BDS-II scoring system, and support clinical
      utility of the instrument with nongeriatric patients. Specifically, the Motor
      Programming Factor and Environmental Independence Factor were more impaired among
      patients with severe, as compared to mild to moderate, TBIs. In contrast, the
      Fluid Intelligence Factor was more impaired among patients with frontal, as
      compared to nonfrontal, injuries. However, when patients were categorized by
      severity, lesion location differences on the BDS total score and factors were
      found only for patients with mild to moderate injuries. Similarly, when patients
      were categorized by lesion location, severity effects were only present among the
      nonfrontal group. Receiver Operating Characteristic curves demonstrated
      sensitivity and specificity rates that ranged from 60% to 100% for clinically
      meaningful cutting scores.

PMID- 15168915
TI  - Cognitive deficits and social functioning in schizophrenia: a clinical
      perspective.
AB  - Impaired social functioning is one of the diagnostic features of schizophrenia.
      Cognitive functioning is also often impaired in several domains. Meta-analysis
      has shown a predictive value of cognition for a variety of domains related to
      social functioning (Green, Kern, Braff, & Mintz, 2000). The significance of these
      findings for clinical practice has remained largely uninvestigated, however, and
      is therefore taken up here. We investigated verbal memory, attention and
      executive functioning in 52 schizophrenia patients. Social functioning was
      assessed for different types of social roles. The percentages of cognitive and
      social impairments in our group were assessed according to clinical principles,
      normally used to judge an individual patient. A possible predictive relationship
      between cognition and social functioning was studied on the basis of these
      clinical criteria. A large proportion of patients showed impairments in both
      cognitive functioning and social functioning. However, the clinical method
      resulted in a successful prediction of social functioning in only 21-69% of the
      cases. Social functioning and cognitive functioning were impaired in a large
      proportion of patients, but were largely independent from each other. Since
      relationships between cognition and social functioning are weak, assessment
      procedures are inconsistent and possibly not optimally adjusted to the
      psychiatric population, the clinical relevance of cognitive testing in order to
      predict social functioning is as yet questionable.

PMID- 15168916
TI  - Performance of cognitively normal African Americans on the RBANS in community
      dwelling older adults.
AB  - Recent research suggests that cognitively normal African Americans are more
      likely to be misdiagnosed as impaired compared to Caucasians due to lower
      neuropsychological test scores (e.g., Manly et al., 1998). Given this, the
      present study sought to determine whether such racial discrepancies exist on the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
      Performances of 50 cognitively normal older African Americans on the RBANS were
      compared to those of 50 Caucasians matched on age, education, and gender. The
      African Americans scored significantly lower on 10 of 12 subtests, 3 of 5 Index
      scores, and the Total Scale score. Results underscored the utility of
      demographically appropriate norms when serving minority clients. Given that there
      remains a paucity of normative data for minority groups, RBANS normative data for
      older African Americans are provided. Although preliminary, it is hoped that data
      presented will offer the practitioner assistance with clinical diagnosis and
      decision-making in a manner that will help minimize diagnostic errors.

PMID- 15168914
TI  - Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part
      II: Comparison to other measures of executive functioning.
AB  - The clinical utility of the Behavioral Dyscontrol Scale (BDS) was compared to
      that of verbal fluency, the Trail Making Test, and the Stroop Color-Word Test, as
      well as measures of processing speed/cognitive efficiency and manual dexterity.
      The ability of these measures to classify 49 TBI patients into frontal versus
      nonfrontal and mild to moderate versus severe groups was examined. The results
      showed that the Fluid Intelligence Factor of the BDS improved classifications
      above and beyond traditional executive measures, but was particularly successful
      at classifying patients who sustained mild injuries. In contrast, traditional
      executive instruments were successful at lesion location classifications only
      among the patients with severe injuries. Severity classifications were successful
      both for traditional measures of processing speed/cognitive efficiency and for
      the Motor Programming Factor of the BDS, but only among patients with nonfrontal
      injuries. These results demonstrate that severity of injury may be an important
      moderator of tests' sensitivity to frontal lobe involvement.

PMID- 15168917
TI  - Using the Halstead-Reitan Battery to diagnose brain damage: a comparison of the
      predictive power of traditional techniques to Rohling's Interpretive Method.
AB  - The aim of this project was to validate an alternative global measure of
      neurocognitive impairment (Rohling Interpretive Method, or RIM) that could be
      generated from data gathered from a flexible battery approach. A critical step in
      this process is to establish the utility of the technique against current
      standards in the field. In this paper, we compared results from the Rohling
      Interpretive Method to those obtained from the General Neuropsychological Deficit
      Scale (GNDS; Reitan & Wolfson, 1988) and the Halstead-Russell Average Impairment
      Rating (AIR; Russell, Neuringer & Goldstein, 1970) on a large previously
      published sample of patients assessed with the Halstead-Reitan Battery (HRB).
      Findings support the use of the Rohling Interpretive Method in producing summary
      statistics similar in diagnostic sensitivity and specificity to the traditional
      HRB indices.

PMID- 15168918
TI  - Assessing visuoconstructional performance in AD, MCI and normal elderly using the
      Beery Visual-Motor Integration Test.
AB  - This study evaluated the Beery Visual-Motor Integration Test (VMI) as a measure
      of construction ability in Alzheimer's disease (AD) and mild cognitive impairment
      (MCI). Construction deficits are an early sign of Alzheimer's disease. Commonly
      used tests of construction abilities are complex, often intimidating to impaired
      elders, and lack a range of items. The VMI has items ranging from very easy to
      difficult, allowing even impaired patients to enter task set, and elderly norms
      are available. It has not yet been validated for use in diagnosis of AD or MCI.
      Two patients groups (n = 43 MCI and 40 AD) recruited from a memory clinic and a
      non-demented control group (n = 43) recruited from the community were
      administered a battery of neuropsychological measures including the VMI. Results
      revealed that the VMI is useful for discriminating AD from MCI. Qualitative
      errors produced on the VMI provide additional information beyond the standard
      score about the patient's cognitive status.

PMID- 15168919
TI  - Changes in neuropsychological test performance over the workday in multiple
      sclerosis.
AB  - Fatigue, a common symptom of multiple sclerosis (MS), is associated with
      impairment in performing daily activities, poor quality of life and premature
      retirement from the workforce. There is little doubt that patients with MS can
      exhibit marked weakness and other objective signs of physical fatigue, but
      whether cognitive performance by patients declines more rapidly than that by
      controls as a function of time engaged in mental activity remains controversial.
      Krupp and Elkins (2000) reported more rapid deterioration of performance by MS
      patients on two of five cognitive measures when subjects performed 3 hr of
      continuously effortful tasks between baseline and posttest. Others, using shorter
      and less taxing interpolated tasks found similar changes in performance over time
      for patients and controls. In the present study participants completed a timed
      walk, fatigue ratings and four cognitive tests that emphasized processing novel
      information before they went to work and again after completing a normal workday.
      Patients with MS walked somewhat more slowly and performed more poorly on two of
      the cognitive tests, but they did not show more decline from baseline to posttest
      on any of these objective measures of cognitive fatigue. By contrast, subjective
      ratings of fatigue showed a greater increase over the day for patients than for
      controls. These results confirm other reports that patients' subjective ratings
      of their fatigue are not valid indicators of their actual performance on
      cognitive tests. Furthermore, laboratory studies that report "objective"
      cognitive fatigue in MS may utilize conditions that model the cognitive fatigue
      associated with the jobs patients actually perform rather poorly.

PMID- 15168920
TI  - Premorbid clues? Preinjury scholastic performance and present neuropsychological
      functioning in late postconcussion syndrome.
AB  - Neuropsychologists rely on demographic variables to form assumptions about
      premorbid status, and most use years of education as the main variable. School
      records are a more objective basis for such estimation, particularly in litigated
      cases. In the present study, final cumulative grade point average (GPA) was
      regressed on to Halstead-Reitan Battery (HRB), IQ and other neuropsychological
      test scores in 60 nonmalingering postconcussive litigants and 17 litigants with
      moderate-severe closed head injury. Results indicated significant correlations
      between GPA, HRB core tests, commonly used neuropsychological measures, and
      intelligence. A regression formula indicated litigants with poor grade point
      average were likely to perform in the impaired range. The present findings
      suggest the quality of premorbid academic performance also provides an important
      context in which to view present neuropsychological performance. Marginal
      premorbid achievement may be a risk factor for late developing postconcussion
      syndrome and litigation.

PMID- 15168921
TI  - Definite malingered neurocognitive dysfunction in moderate/severe traumatic brain
      injury.
AB  - There has been disagreement in the literature about whether persons with
      documented neuropathology can be diagnosed as malingering. To address this
      question, we present three moderate severe traumatic brain injury patients who
      were evaluated in the context of litigation who met the Slick, Sherman, and
      Iverson (1999) criteria for a diagnosis of "Definite Malingered Neurocognitive
      Dysfunction." Each performed significantly below-chance on at least one forced
      choice symptom validity test, thereby demonstrating a deliberate attempt to
      appear impaired. These cases represent the first definitive evidence of an
      intentional effort to appear impaired in the context of documented
      moderate/severe traumatic brain injury.

PMID- 15168923
TI  - [The next step for REDAR: achieving an impact factor].

PMID- 15168922
TI  - The Memory Assessment Scales in the detection of incomplete effort in mild head
      injury.
AB  - Despite differences in the constructs measured, the Memory Assessment Scales
      (MAS) remain an alternative to the Wechsler Memory Scales (WMS) as a broad-band
      instrument for assessing multiple aspects of attention and memory. Although a
      number of studies have examined indices of the WMS as indicators of malingering,
      few studies have similarly investigated the MAS. In this study, we examined the
      degree to which the MAS was effective in detecting incomplete effort in a
      clinical sample of patients referred for neuropsychological evaluation after mild
      head injury. Included in the sample were 21 financially compensable (FC)
      participants with alleged mild head injury and 21 participants who were not
      involved in litigation and suffered more serious head injuries. Examination of
      the four MAS domain indices indicated that Short-Term Memory was most useful at
      identifying incomplete effort. We also examined subscales of the MAS. Consistent
      with previous findings, brief tests such as Verbal and Visual Span had high rates
      of diagnostic sensitivity and specificity. Although tests based on a forced
      choice recognition paradigm (e.g., Immediate and Delayed Visual Recognition)
      predicted group membership above chance levels, they failed to significantly add
      to prediction above Verbal and Visual Span subtests.

PMID- 15168924
TI  - [Never have so few done so much for so many].

PMID- 15168925
TI  - [Precurarization with rocuronium prevents fasciculations and biochemical changes
      after succinylcholine administration].
AB  - OBJECTIVE: To determine the efficacy of rocuronium to prevent fasciculations and
      biochemical changes after succinylcholine administration. PATIENTS AND METHODS:
      Prospective, randomized double-blind trial enrolling 60 ASA I-II patients
      scheduled for elective surgery under general anesthesia. The patients were
      assigned to 2 groups to receive either 0.06 mg x Kg(-1) of rocuronium or
      physiological saline solution 90 seconds before administration of 1.5 mg x Kg(-1)
      of succinylcholine. The incidence and severity of fasciculations and serum
      concentrations of potassium before anesthesia and 3, 5, and 20 minutes after
      succinylcholine administration were recorded. Other serum concentrations recorded
      were myoglobin, creatinine phosphokinase and lactate before anesthesia and 20
      minutes after succinylcholine administration. RESULTS: The increases in potassium
      levels at 3 and 5 minutes (0.3 +/- 0.3 and 0.2 +/- 0.4 mmol x L(-1)) and in
      myoglobin levels at 20 minutes (38.9 +/- 31.7 ng x mL(-1)) were attenuated by
      precurarization with rocuronium. The incidence of fasciculations was
      significantly lower (p<0.001) and their severity significantly less (p<0.001) in
      patients who received rocuronium before administration of succinylcholine.
      CONCLUSIONS: Precurarization with rocuronium 90 seconds before succinylcholine
      administration reduces the incidence and severity of fasciculations and prevents
      increases in serum potassium and myoglobin concentrations.

PMID- 15168926
TI  - [Fentanyl or remifentanil to potentiate a single dose of rocuronium in patients
      anesthetized with propofol with evaluation by accelerometry].
AB  - OBJECTIVE: To compare the increase in potency of a single dose of rocuronium
      during anesthesia with propofol combined with either fentanyl or remifentanil.
      PATIENTS AND METHODS: Forty patients scheduled for plastic surgery were
      distributed in 2 groups of 20 according to the opioid drug assigned: fentanyl or
      remifentanil. Induction with propofol was accomplished by computer-controlled
      infusion, with response measured in the adductor pollicis muscle. After
      calibration, a dose of 0.6 mg/Kg of rocuronium was infused. Anesthesia was
      maintained with propofol, oxygen in air, and an equipotent dose of either
      fentanyl or remifentanil, which was modified to maintain heart rate and systolic
      arterial pressure within 30% above or below baseline levels. Patient
      characteristics recorded were age, sex, height, weight, ASA class, type of
      surgery, and the propofol and opioid doses consumed. Intubation conditions and
      time to onset of action of rocuronium (T1), of recovery of the first response in
      a train of four (RT1), and of recovery of 25% of the first response or clinical
      duration. RESULTS: The groups were statistically similar in terms of demographic
      variables, type of surgery, propofol and opioid consumption, intubation
      conditions, and rocuronium T1 and RT1. Clinical duration of anesthesia was longer
      (p<0.05) in the remifentanil group (33.1 +/- 10 minutes) than in the fentanyl
      group (27.1 +/- 7.4 minutes). CONCLUSIONS: Remifentanil administered in
      combination with propofol for anesthesia does not affect time of onset of a
      single dose of 0.6 mg/Kg dose of rocuronium, but clinical duration of anesthesia
      is longer with remifentanil and propofol than with the fentanyl and propofol
      combination. The surgical and intubation conditions achieved with both
      combinations are adequate and similar.

PMID- 15168927
TI  - [Influence of the severity of obesity on morbidity and mortality after gastric
      bypass surgery].
AB  - OBJECTIVE: To determine the influence of severity of obesity on morbidity and
      mortality following Roux-en-Y gastric bypass and vertical ringed gastroplasty,
      with severity classified as morbid obesity (MO) defined by a body mass index
      (BMI) between 35 and 55 Kg/m2 and super-morbid obesity (SMO) defined by a BMI
      exceeding 55 Kg/m2. METHOD: A series of patients who underwent the aforementioned
      type of gastric bypass surgery were followed for 5 years. The patients were
      classified as to whether they had associated sleep apnea syndrome, alveolar
      hypoventilation, or "overlap syndrome". RESULTS: A total of 105 patients were
      enrolled: 70 (66.7%) classified as having MO and 35 (33.3%) classified as having
      SMO. Distribution by sex was significantly different in the 2 groups, but
      respiratory diseases were similar. PaO2 was higher in the MO group, PaCO2 was
      lower, and the alveolar-arterial gradient was smaller. Duration of surgery was
      shorter in the MO group (120.43 +/- 32.97 vs. 136.76 +/- 28.28 minutes). The
      percentage of complications was similar in the 2 groups (32.86% and 45.7% in the
      MO and SMO groups, respectively), although the incidence of respiratory
      complications was higher in SMO patients (8.57% vs. 20% in the MO and SMO groups,
      respectively). No differences were observed in the rates of surgical,
      hemodynamic, or infectious complications. Length of hospital stay was similar
      (6.44 vs. 6.69 for MO and SMO patients, respectively). CONCLUSIONS: More severe
      obesity can be associated with preoperative arterial blood gas alterations in
      patients with concomitant respiratory disease and a higher incidence of
      respiratory complications in the early phase of recovery from gastric bypass
      surgery.

PMID- 15168928
TI  - [A review of clinical evidence supporting techniques to prevent chronic
      postoperative pain syndromes].
AB  - OBJECTIVE: To conduct a systematic review to evaluate the level of evidence for
      using acute postoperative pain management techniques with a view to pre-empting
      the later development of chronic pain syndromes. MATERIAL AND METHODS: Systematic
      review of the literature on the treatment of acute postoperative pain and its
      usefulness in preventing postoperative chronic pain syndromes. RESULTS: Fifteen
      studies focusing on 3 conditions were examined: chronic postmastectomy pain
      syndrome, chronic postthoracotomy pain syndrome, and chronic phantom limb pain.
      Four clinical trials provided no clear evidence of benefit from preoperative
      injections of local anesthetic in decreasing the incidence of chronic
      postmastectomy pain. Continuous thoracic epidural analgesia started before
      surgery has been shown to have a clearly beneficial effect in preventing chronic
      pain 3, 6, and 12 months after thoracotomy. Chronic phantom limb pain syndromes
      have not been found to be prevented by the use of continuous epidural analgesia
      started before or after surgery in comparison with the injection of local
      anesthetics through a perineural catheter or the oral or intramuscular
      administration of morphine-like drugs. CONCLUSIONS: Only chronic pain following
      thoracotomy has been found to be preempted by acute pain management and only by
      continuous thoracic epidural analgesia started before surgery. There is no solid
      evidence demonstrating that other techniques used to relieve acute postoperative
      pain have a beneficial effect in preempting chronic postoperative pain syndromes.

PMID- 15168929
TI  - [Prolonged interscalene block to treat postoperative brachial plexopathy].
AB  - A 47-year-old woman developed neuropathic pain in the right brachial plexus after
      surgery to remove a suprasellar tumor. The main cause was injury to the plexus
      owing to technical difficulties in the preoperative catheterization of the
      ipsilateral internal jugular vein. The pain, which was intense and refractory to
      systemic medication, resolved with a continuous interscalene block with
      ropivacaine, clonidine, and morphine. The block was continued throughout the
      rehabilitation period, which lasted 7 weeks to allow recovery with no sequelae.
      Perioperative neuropathy is a rare but potentially debilitating complication.
      Injury to the brachial plexus causes neuropathic type pain. Consequent functional
      changes are difficult to treat and have significant repercussions on quality of
      life. Current approaches to treatment reduce both central and peripheral neuronal
      hyperexcitability. A continuous regional block of the brachial plexus to manage
      refractory neuropathic pain is an effective technique that is seldom mentioned in
      the literature.

PMID- 15168930
TI  - [Cesarean delivery and exeresis of a pheochromocytoma performed under epidural
      and general anesthesia].
AB  - A 33-year-old pregnant woman with episodes of nocturnal tachycardia and anxiety
      diagnosed with extra-renal pheochromocytoma in her 28th month of gestation was
      admitted in her 38th week for an alpha-adrenergic block prior to elective
      cesarean section and tumor exeresis. The cesarean section was performed with the
      patient given an epidural lumbar block, and immediately after delivery of the
      fetus total intravenous anesthesia (with propofol, remifentanil, and rocuronium)
      was administered in addition to the continuous epidural analgesia used during
      tumor resection and postoperatively. No complications developed during surgery or
      recovery and the clinical courses were satisfactory for both mother and child.
      The use of propofol and remifentanil in combination with epidural anesthesia is
      not common in our clinical context. We point out that the multimodal technique
      affords good hemodynamic stability, guarantees satisfactory analgesia, and
      reduces the need for vasoactive drugs.

PMID- 15168931
TI  - [Anesthesia for cesarean delivery in a woman with congenital aortic stenosis].
AB  - The patient was a 26-year-old primipara diagnosed in the first trimester with
      aortic stenosis and coarctation of the descending aorta. She had remained stable
      until the 37th week, when she developed dyspnea, edema in the lower extremities,
      crepitations, oliguria, hypotension, and mild sinus tachycardia consistent with
      left ventricular insufficiency. A cesarean was performed under general anesthesia
      with remifentanil, with good outcomes for mother and infant. Aortic stenosis
      causes left ventricular hypertrophy that increases the risk of myocardial
      ischemia and left ventricular insufficiency in combination with the physiological
      changes that pregnancy produces in the cardiovascular system. An emergency
      cesarean section in such patients requires preservation of hemodynamic stability,
      which is difficult to achieve with epidural or subarachnoid techniques.
      Remifentanil is an alternative to drugs used until now in this context.

PMID- 15168932
TI  - [Sayings about pain in Don Quijote].

PMID- 15168933
TI  - [Peripartum myocardiopathy in a woman with acquired immunodeficiency syndrome].

PMID- 15168935
TI  - [Spinal anesthesia and tattoos].

PMID- 15168934
TI  - [Acute dystonia due to haloperidol during labor].

PMID- 15168936
TI  - [Capnography trace with two plateaus due to water trap failure].

PMID- 15168938
TI  - [Single lung ventilation with the Arndt endobronchial blocker for esophageal
      surgery].

PMID- 15168937
TI  - [Activated protein C and cardioversion].

PMID- 15168939
TI  - [Regional anaesthesia versus general anaesthesia--pathophysiology and clinical
      implications].
AB  - Regional anaesthesia is well established in modern clinical practice. It provides
      a safe and reliable alternative to general anaesthesia, but is also of high
      clinical value in combination procedures. Our knowledge of perioperative
      pathophysiological characteristics increasingly indicates that regional blocks
      lead to excellent analgesia und profoundly modulate the postoperative stress
      response and thus, they can have therapeutic influence on postoperative
      convalescence, on the functional operation result and on the avoidance of
      frequent postoperative complications. Given the increasing number of older
      patients with nigher co-morbidity, this is of particular therapeutic importance,
      but also has economic implications. The continuous techniques of regional
      anaesthesia, which at first sight are more time-consuming and expensive, may
      shorten the time to extubation after major abdominal procedures, accelerate
      postoperative recovery and prevent postoperative adverse outcomes. Optimised
      physiotherapy after total knee arthroplasty or improvements in pulmonary and
      gastrointestinal function demonstrate the capabilities of regional anaesthesia to
      facilitate postoperative rehabilitation. With regard to an improved organ
      function and a possibly shorter hospital stay, regional techniques appear cost
      effective. It is important that regional anaesthesia is carried out on the basis
      of a clear individual indication, which considers the entire perioperative
      treatment process.

PMID- 15168941
TI  - [The influence of normobaric hyperoxia on hepatic oxygenation--experience with an
      animal model].
AB  - We investigated the effect of a ventilation with an FiO2 of 1.0 on arterial and
      hepatic venous oxygenation in 23 Gottingen minipigs. Under balanced anaesthesia
      (isoflurane/fentanyl), a fibreoptic catheter was placed into a hepatic vein. The
      correct position of the tip of the catheter was controlled manually after
      laparotomy. After measurement of baseline values (arterial and hepatic blood
      gases, ShvO2), in 13 minipigs normoventilation with an FiO2 of 1.0 was performed
      for 15 minutes. Thereafter, ventilation was continued with an FiO2 of 0.4. In the
      control group (n = 10), the animals were oxygenated with an FiO2 of 0.4
      permanently. The changes due to hyperoxia were measured in hepatic venous oxygen
      saturation (ShvbgaO2: from 81.2 +/- 1.43% to 87.5 +/- 1.77%, ShvoximO2: from 82.6
      +/- 1.14% to 90.5 +/- 0.90%), arterial (from 217.5 +/- 5.0 mmHg to 467.2 +/- 22.0
      mmHg) and hepatic venous (from 51.8 +/- 2.0 mmHg) oxygen partial pressure. We
      found a correlation between hepatic venous oxygen partial pressure und ShvbgaO2
      in the blood (r = 0.84, p < 0.001) and between ShvO2 (ShvbgaO2/ShvoximO2), which
      was either measured directly in the blood or by a fibreoptic catheter (r = 0.6, p
      < 0.001). Whereas the increase in ShvO2 during hyperoxia may be a result of
      increased arterial supply, the decrease in ShvO2 after the end of hyperoxia below
      baseline values needs further investigations. The continuous fibreoptic
      measurement of ShvoximO2, also under hyperoxic conditions is a valuable parameter
      for the monitoring of hepatic venous oxygenation.

PMID- 15168940
TI  - [Analgesia, sedation and anaesthesia in emergency service].
AB  - Skilful analgesia is self-explanatory and needs no justification. In contrast to
      this, preclinical general anaesthesia is of relative value and depends, in part,
      on the professional qualities of the emergency physician. Analgesic and
      anaesthestic drugs should be administered via a safe intravenous line. In
      contrast to rapid sequence induction of general anaesthesia, analgesic drugs
      should be titrated. The patient has to be monitored by the vigilance of the
      physician and adequate technical equipment. Metamizol is used for treatment of
      minor and medium pain, while morphine is indicated for treatment of major pain,
      especially in internal patients. Fentanyl is mainly used for total intravenous
      anaesthesia with controlled ventilation. (S)-ketamine is indicated for analgesia,
      analgosedation and anaesthesia in trauma patients, except isolated or dominating
      craniocerebral trauma, and in special internal cases. Midazolam is used for
      sedation or, in combination with (S)-ketamine or fentanyl, total intravenous
      anaesthesia. Etomidate is especially useful for induction of emergency patients
      with sufficient cardiovascular stability. Suxamethonium is the standard relaxant
      for endotracheal intubation during rapid sequence induction. If longer muscle
      relaxation is necessary, vecuronium should be used due to its simple storage and
      general lack of untoward effects. Butylscopolamin is used in colic pain, either
      alone or in combination with analgesic drugs. Haloperidol is indicated in acute
      psychotic syndromes as well as psychomotoric and alcohol-dependent excitation. On
      the whole, profound pharmacological and practical knowledge is necessary,
      although restricting oneself to just a few drugs increases the depth of one's
      personal experience.

PMID- 15168942
TI  - [Perioperative management of a patient with alcaptonuria--a case report].
AB  - Alcaptonuria is a very rare enzymatic disease with a compromised degradation of
      the amino acids phenylalanine and tyrosine. As a consequence, homogentisic acid
      accumulates, most of which is cleared by the kidneys. In time, homogentisic acid
      forms black pigment, which accumulates throughout the body in connective tissue
      such as cartilage and joints. Apart from superficial discoloration, the most
      clinical manifestation of the disease is arthropathy, starting in middle age.
      From the anaesthesiologist's point of view, there is a severe risk of difficult
      airway because of an advanced stiffness of the cervical spine and a reduced mouth
      opening in these patients. Due to deformity and stiffness of the spine,
      difficulties in spinal and epidural anaesthesia must be reckoned with. A further
      risk for patients with alcaptonuria is cardiac involvement, which occurs later
      than degenerative changes of the joints. The accumulated pigment most likely adds
      to the development of degenerative changes of the valve and coronary artery
      disease and there is an increased risk of developing aneurysms in atherosclerotic
      altered vessels. Therefore, at the preoperative visit a thorough clinical
      cardiovascular examination should be performed. Cardiological advice and an
      examination should be sought from a specialist. For intubation, fibreoptic
      procedures should be considered. Anaesthetic management and perioperative
      monitoring are determined by the results of the cardiological examination and the
      type and extent of the operation.

PMID- 15168943
TI  - Differential gene expression in anthracene-exposed mummichogs (Fundulus
      heteroclitus).
AB  - The polycyclic aromatic hydrocarbon (PAH) anthracene is present in many estuarine
      systems at concentrations believed to cause sublethal adverse effects, although
      its exact mode of toxicity remains unclear. Knowledge of the induction or
      suppression of specific genes as a result of exposure may be useful in explaining
      these effects. We have generated a fingerprint of anthracene exposure using the
      mummichog (Fundulus heteroclitus), a non-migratory estuarine fish species. The
      fish were exposed in 7-day static renewal tests to environmentally relevant
      concentrations of 0, 27, 50, and 80 microg/l of anthracene. Total RNA was
      extracted from the livers and differential display reverse transcription
      polymerase chain reaction (DD RT-PCR) was used to recover 26 differentially
      expressed cDNA fragments. These cDNAs were isolated, sequenced, and compared to
      sequences of known genes in order to identify possible physiological consequences
      of exposure to anthracene. We then constructed macroarrays using these fragments
      and probed them with RNA from both anthracene-exposed fish and fish from a known
      PAH-impacted site. Three genes appear to be good indicators of exposure to
      anthracene in the range of concentrations tested, which included CYP2N2 and two
      expressed sequence tags (ESTs) termed 15C1 and 18C2. The expression of nine genes
      was altered in fish collected from a site with multiple PAHs. Band 15C1 and
      CYP2N2 again showed statistically significant upregulation in the field-caught
      fish, while a trypsin precursor and fatty acid-binding protein (FABP) all showed
      similar trends in induction as the laboratory-exposed fish. Further insight into
      the mechanism of toxicity of contaminants will be gained by the ability to
      identify and use differentially expressed genes as markers of exposure and
      effects.

PMID- 15168944
TI  - Development and application of a real-time quantitative PCR assay for determining
      CYP1A transcripts in three genera of salmonids.
AB  - The expression of CYP1A (cytochrome P4501A) can be induced by a large array of
      aromatic and organic compounds in teleost fishes. We developed a real-time
      quantitative PCR assay useful for measuring beta-naphthoflavone (BNF) induction
      of liver CYP1A mRNA in four salmonid species. First, to obtain necessary
      information for the design of a cRNA standard, full-length CYP1A cDNA sequences
      were determined for two Salvelinus species, lake trout (S. namaycush) and brook
      trout (S. fontinalis). Each cDNA was found to share the same characteristics with
      known CYP1A sequences of Atlantic salmon (Salmo salar) and rainbow trout
      (Oncorhynchus mykiss): a start codon, conserved heme-binding region, putative
      poly-adenylation signal, stop codon, relatively long 3'-untranslated region (UTR;
      >1 kb), and a protein length of 523 amino acid residues. The brook trout and lake
      trout CYP1A cDNA's were 2636 and 2672 base pairs (bp) in length and shared
      greater than 97% coding region sequence identity with Atlantic salmon and rainbow
      trout CYP1A's. Next, using the generated sequence information, we developed a
      CYP1A-specific real-time quantitative PCR assay. Primers and a fluorescent
      labeled probe were designed from a 68 bp region that was found to be conserved
      among salmonid CYP1A genes. The assay was designed to allow for simultaneous
      comparison of CYP1A expression among each experimental group. Finally, groups (n
      = 4-8) of hatchery-raised Atlantic salmon, brook trout, lake trout, and rainbow
      trout were given an intraperitoneal injection of a corn oil control, 25 mg kg(-1)
      BNF, or 50 mg kg(-1) BNF and sacrificed after 48 h. Liver tissue was collected
      and CYP1A mRNA levels were estimated. In all species, BNF treated fish showed 1.8
      3.0 orders of magnitude higher CYP1A than control fish. The CYP1A induction
      levels were not different in fish treated with both dosages. Mean base levels of
      CYP1A expression ranged from 7.24 x 10(6) (rainbow trout) to 1.05 x 10(7) (brook
      trout) transcripts microg(-1) total RNA. Mean induced levels of CYP1A expression
      ranged from 1.07 x 10(8) (lake trout) to 1.05 x 10(9) (brook trout) trancripts
      microg(-1) total RNA.

PMID- 15168945
TI  - Effects of atrazine on sex steroid dynamics, plasma vitellogenin concentration
      and gonad development in adult goldfish (Carassius auratus).
AB  - Sexually mature goldfish (Carassius auratus) of both sexes were exposed to two
      doses (100 and 1000 microg/l) of the widely used herbicide atrazine (2-chloro-4
      ethylamino-6-isopropylamino-s-triazine) for a period of 21 days and effects on
      the concentrations of gonad and plasma sex steroids (testosterone (T), 17beta
      estradiol (E2) and 11-ketotestosterone (11-KT)), plasma vitellogenin (VTG) and
      gonad histo-morphology assessed. Atrazine did not show any obvious estrogenic
      effect in males, as determined by a lack of vitellogenin induction. There were,
      however, effects of atrazine on plasma androgen concentrations (androgen
      dynamics) and tissue (plasma and gonad) estrogen concentrations in male goldfish;
      exposure to 1000 microg/l atrazine induced suppression in both testosterone and
      11-ketotestosterone, and resulted in elevated 17beta-estradiol, after 21 day of
      exposure. Further, these suppressive effects on plasma androgens and the
      induction in estrogen were dose- and time-related. The highest atrazine exposure
      dose induced structural disruption in the testis and both 100 and 1000 microg/l
      induced elevated levels of atresia in ovaries.

PMID- 15168946
TI  - Application of the comet and micronucleus assays to the detection of B[a]P
      genotoxicity in haemocytes of the green-lipped mussel (Perna viridis).
AB  - Green-lipped mussels (Perna viridis) were exposed to water-borne benzo[a]pyrene
      (B[a]P) at nominal concentrations of 0, 0.3, 3 and 30 microg l(-1) for up to 12
      days, and both the relative levels of DNA strand breaks (assessed using an
      alkaline comet assay) and the proportion of micronucleus (MN) formation were
      monitored in mussel haemocytes at days 0, 1, 3, 6 and 12. The results of the
      comet assay indicated that an increase in the proportion of strand breaks
      occurred generally with increasing B[a]P concentration, but a significant
      decrease in the levels of DNA damage was observed after exposure for 12 days at
      all concentrations tested, suggesting that the patterns of changes in the levels
      of DNA strand breakage can be explained by the threshold dependent DNA repair
      theory. Moreover, the relatively slow development and recovery of the DNA damage
      response in mussel haemocytes in comparison with previous findings utilizing P.
      viridis hepatopancreas suggests that the response of DNA alteration upon exposure
      to B[a]P may be tissue-specific in this species. Monitoring the frequency of
      micronucleus development in mussel haemocytes indicated both dose- and time
      response relationships within the exposure period. Furthermore, the levels of DNA
      strand breakage correlated well with the levels of micronucleus induction,
      suggesting a possible cause and effect relationship between the two damage types.
      We suggest that DNA strand breakage and micronucleus formation in mussel
      haemocytes can potentially be used as convenient biomarkers of exposure to
      genotoxicants in the marine environment.

PMID- 15168947
TI  - High sensitivity of northern pike larvae to UV-B but no UV-photoinduced toxicity
      of retene.
AB  - In order to investigate whether increased UV-B radiation is a risk factor, a
      series of acute laboratory experiments was conducted with larval stages of the
      northern pike (Esox lucius L.), hatching in Nordic waters in May. Further, a
      comparative investigation on the acute phototoxicity of retene (7-isopropyl-1
      methylphenanthrene), a PAH compound recently revealed to posses UV-B-induced
      phototoxicity in larval coregonids, was conducted with pike larvae. In semi
      static experiment, larvae were pre-exposed to retene (3, 9, 30 and 82 microg/g),
      with relevant controls, for 24 h and then irradiated for 3 h once a day (two
      consecutive days) with three UV-B doses (CIE-weighted 1.0, 1.8 or 2.7 kJ/m2 per
      day) or with visible light only. In 3 days, the UV-B exposure alone increased
      mortality by 10-20% in all applied dose rates. Retene (up to 82 microg/l) had no
      direct UV-B-induced toxicity in pike. However, pike larvae were very sensitive to
      UV-B even in low doses, indicated as severe neurobehavioral disorders. Monitoring
      of pike with the neurobehavioral syndrome revealed substantial late mortality. As
      UV-B had no influence on CYP1A content in larval pike, retene (9-82 microg/l)
      induced this protein substantially with and without UV-B. In pike, the applied UV
      B radiation and water retene alone both decreased HSP70 concentrations. Neither
      UV nor retene changed SOD activity significantly. Overall, data on pike suggest
      that only a minor increase in ambient UV-B coming to the earth's surface may
      cause lethal effects to larval fish.

PMID- 15168948
TI  - Analysis of the importance of lipid breakdown for elimination of okadaic acid
      (diarrhetic shellfish toxin) in mussels, Mytilus edulis: results from a field
      study and a laboratory experiment.
AB  - Okadaic acid (OA) is a lipophilic phycotoxin, which accumulates in the digestive
      organs of mussels and may cause diarrhetic shellfish poisoning (DSP) in humans.
      Depuration of toxic mussels is a potential option for the shellfish industry to
      increase the availability of marketable mussels. To develop cost-effective
      depuration methods for DSP toxins, knowledge about the environmental conditions
      and physiological processes regulating the rate of depuration is essential. In
      this paper, the importance of lipid breakdown for elimination of OA in mussels
      was investigated by performing a field study and a manipulative laboratory
      experiment. First, total lipid content and concurrent concentration of OA in the
      digestive glands of farmed blue mussels, Mytilus edulis, was analysed on a
      monthly basis from January to June 2000. A significant positive correlation
      between levels of OA and lipid content was observed between January and March,
      when lipid levels were showing a decreasing trend. This supported a previously
      proposed model that breakdown of lipid stores may affect the release and
      elimination of this lipophilic toxin. To test this causal model, a laboratory
      experiment was performed. Mussels containing OA were exposed to experimental
      treatments (increased seawater temperature and/or food limitation) for 24 days in
      order to increase the energy requirements and need to use lipids as an energy
      source. It was predicted that mussels exposed to these treatments would have a
      faster elimination rate of OA compared to feeding mussels kept in ambient
      seawater temperature. The results showed that lipid content was significantly
      reduced in mussels exposed to an increased water temperature (24 degrees C)
      compared to ambient temperature (18 degrees C). The amount of lipids was not
      affected by food limitation. Although lipid content was reduced in 24 degrees C,
      the rate of depuration of OA was not faster for mussels in this treatment and no
      correlation was detected between lipid content and OA. Depuration rates were very
      similar for all treatments and followed an exponential decrease relationship
      (t(1/2) = 8 days). Thus, the proposed model that lipid breakdown affects the
      mechanism of elimination of OA was not supported. Nevertheless, the observed
      rates of depuration provide useful information and a potential predictive tool
      for large-scale depuration methods of mussels. The difficulties to influence the
      rate of depuration of this toxin by changing the environmental conditions suggest
      that processes, insensitive to short-term manipulation of the external
      environment, regulate depuration of OA.

PMID- 15168949
TI  - Malathion immunotoxicity in the American lobster (Homarus americanus) upon
      experimental exposure.
AB  - A lobster die-off reduced the 1999 fall landings in western Long Island Sound by
      up to more then 99%. The die-off corresponded in time with the application of
      pesticides for the control of mosquitoes that carried West Nile virus, a new
      emerging disease in North America at the time. In order to determine the possible
      implication of pesticide application as a direct cause or contributing factor in
      the die-off, we studied the effects of experimental exposure to malathion on the
      health of lobsters. Lobsters were exposed in 20 gallon tanks, and the direct
      toxicity as well as sub-lethal effects on the immune system were determined. The
      96 h LC50 for malathion upon single exposure was 38 microg/l. Malathion degraded
      rapidly in sea water, with 65-77% lost after 1 day and 83-96% lost after 3 days.
      Phagocytosis was significantly decreased 3 days after a single exposure to
      initial water concentrations as low as 5 ppb, when measured water concentrations
      were as low as 0.55 ppb. Similarly, effects on phagocytosis were observed at 1, 2
      and 3 weeks after the initiation of weekly exposures. Cell counts did not differ
      significantly upon exposure to malathion. Malathion was not detected in muscle
      and hepatopancreas of exposed lobsters. Evaluation of phagocytosis is a sensitive
      indicator of subtle sub-lethal effects of malathion, and relatively small
      concentrations of malathion (6-7 times lower than the LC50) can affect lobster
      defense mechanisms.

PMID- 15168950
TI  - Environmental risk limits for antifouling substances.
AB  - In 1989, the EU restricted the use of tributyl-tin (TBT) and the International
      Maritime Organisation (IMO) decided for a world-wide ban on TBT in 2003. As a
      replacement for TBT, new antifouling agents are entering the market.
      Environmental risk limits (ERLs) are derived for substances that are used as TBT
      substitutes, i.e. the compounds Irgarol 1051, dichlofluanid, ziram,
      chlorothalonil and TCMTB. ERLs represent the potential risk of the substances to
      the ecosystem and are derived using data on (eco)toxicology and environmental
      chemistry. Only toxicity studies with endpoints related to population dynamics
      are taken into account. For Irgarol 1051 especially plants appear to be
      sensitive; the mode of action is inhibition of photosynthetic electron transport.
      Despite the higher sensitivity of the plants, the calculated ERL for water based
      on plants only is higher than the ERL based on all data due to the lower
      variability in the plant only dataset. Because there is a mechanistic basis to
      state that plants are the most sensitive species, we propose to base the ERL for
      water on the plants only dataset. As dichlofluanid is highly unstable in the
      water phase, it is recommended to base the ERL on the metabolites formed and not
      on the parent compound. No toxicity data of the studied compounds for organisms
      living in sediments were found, the ERLs for sediment are derived with help of
      the equilibrium partitioning method. For dichlofluanid and chlorothalonil the ERL
      for soil is directly based on terrestrial data, for Irgarol 1051 and ziram the
      ERL for soil is derived using equilibrium partitioning. Except for Irgarol 1051,
      no information was encountered in the open literature on the environmental
      occurrence in The Netherlands of the chemicals studied. The measured
      concentrations for Irgarol 1051 are close to the derived ERL. For this compound
      it is concluded that the species composition and thereby ecosystem functioning
      cannot be considered as protected.

PMID- 15168951
TI  - What people want from their family physician.
AB  - The public wants and is satisfied by care provided within a patient-physician
      relationship based on understanding, honesty, and trust. If the U.S. health care
      system is ever to become patient-centered, it must be designed to support these
      values and sustain, rather than fracture, the relationships people have with
      their primary physician.

PMID- 15168952
TI  - Few people in the United States can identify primary care physicians.
AB  - Almost one decade after the Institute of Medicine (IOM) defined primary care,
      only one third of the American public is able to identify any of the medical
      specialties that provide it, and only 17 percent were able to accurately
      distinguish primary care physicians from medical or surgical specialists and non
      physicians. This lack of discrimination compromises the goal of achieving primary
      care for all and merits immediate attention.

PMID- 15168953
TI  - Protecting American families from injury.

PMID- 15168954
TI  - Management of newly detected atrial fibrillation.

PMID- 15168955
TI  - How should physicians decide to resuscitate a patient?

PMID- 15168956
TI  - Cryosurgery for common skin conditions.
AB  - Cryosurgery is a highly effective treatment for a broad range of benign skin
      problems. With appropriate instruction and supervised experience, family
      physicians can master the technique quickly. Cryosurgery is best suited for use
      in patients with light skin and for treatment of lesions in most non-hair-bearing
      areas of the body. Spray methods include the timed spot freeze technique, the
      rotary or spiral pattern, and the paintbrush method. Benign skin lesions that are
      suitable for freezing include actinic keratosis, solar lentigo, seborrheic
      keratosis, viral wart, molluscum contagiosum, and dermatofibroma. Cryosurgery
      requires little time and fits easily into the physician's office schedule.
      Advantages of this treatment include a short preparation time, low risk of
      infection, and minimal wound care. In addition, cryosurgery requires no expensive
      supplies or injectable anesthesia, and the patient does not have to return for
      suture removal. Potential side effects include bleeding, blister formation,
      headache, hair loss, and hypopigmentation, but rarely scarring. Skin lesions
      often can be treated in a single session, although some require several
      treatments.

PMID- 15168957
TI  - Depression in later life: a diagnostic and therapeutic challenge.
AB  - Depression in elderly persons is widespread, often undiagnosed, and usually
      untreated. The current system of care is fragmented and inadequate, and staff at
      residential and other facilities often are ill-equipped to recognize and treat
      patients with depression. Because there is no reliable diagnostic test, a careful
      clinical evaluation is essential. Depressive illness in later life should be
      treated with antidepressants that are appropriate for use in geriatric patients.
      A comprehensive, multidisciplinary approach, including consideration of
      electroconvulsive treatment in some cases, is important. The overall long-term
      prognosis for elderly depressed patients is good.

PMID- 15168958
TI  - Management of hyponatremia.
AB  - Hyponatremia is an important electrolyte abnormality with the potential for
      significant morbidity and mortality. Common causes include medications and the
      syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Hyponatremia
      can be classified according to the volume status of the patient as hypovolemic,
      hypervolemic, or euvolemic. Hypervolemic hyponatremia may be caused by congestive
      heart failure, liver cirrhosis, and renal disease. Differentiating between
      euvolemia and hypovolemia can be clinically difficult, but a useful investigative
      aid is measurement of plasma osmolality. Hyponatremia with a high plasma
      osmolality is caused by hyperglycemia, while a normal plasma osmolality indicates
      pseudohyponatremia or the post-transurethral prostatic resection syndrome. The
      urinary sodium concentration helps in diagnosing patients with low plasma
      osmolality. High urinary sodium concentration in the presence of low plasma
      osmolality can be caused by renal disorders, endocrine deficiencies, reset
      osmostat syndrome, SIADH, and medications. Low urinary sodium concentration is
      caused by severe burns, gastrointestinal losses, and acute water overload.
      Management includes instituting immediate treatment in patients with acute severe
      hyponatremia because of the risk of cerebral edema and hyponatremic
      encephalopathy. In patients with chronic hyponatremia, fluid restriction is the
      mainstay of treatment, with demeclocycline therapy reserved for use in persistent
      cases. Rapid correction should be avoided to reduce the risk of central pontine
      myelinolysis. Loop diuretics are useful in managing edematous hyponatremic states
      and chronic SIADH. In all instances, identifying the cause of hyponatremia
      remains an integral part of the treatment plan.

PMID- 15168959
TI  - Diethylstilbestrol exposure.
AB  - Diethylstilbestrol is a synthetic nonsteroidal estrogen that was used to prevent
      miscarriage and other pregnancy complications between 1938 and 1971 in the United
      States. In 1971, the U.S. Food and Drug Administration issued a warning about the
      use of diethylstilbestrol during pregnancy after a relationship between exposure
      to this synthetic estrogen and the development of clear cell adenocarcinoma of
      the vagina and cervix was found in young women whose mothers had taken
      diethylstilbestrol while they were pregnant. Although diethylstilbestrol has not
      been given to pregnant women in the United States for more than 30 years, its
      effects continue to be seen. Women who took diethylstilbestrol during pregnancy
      have a slightly higher risk of breast cancer than the general population and
      therefore should be encouraged to have regular mammography. Women who were
      exposed to diethylstilbestrol in utero may have structural reproductive tract
      anomalies, an increased infertility rate, and poor pregnancy outcomes. However,
      the majority of these women have been able to deliver successfully.
      Recommendations for gynecologic examinations include vaginal and cervical digital
      palpation, which may provide the only evidence of clear cell adenocarcinoma.
      Initial colposcopic examination should be considered; if the findings are
      abnormal, colposcopy should be repeated annually. If the initial colposcopic
      examination is normal, annual cervical and vaginal cytology is recommended.
      Because of the higher risk of spontaneous abortion, ectopic pregnancy, and
      preterm delivery, obstetric consultation may be required for pregnant women who
      had in utero diethylstilbestrol exposure. The male offspring of women who took
      diethylstilbestrol during pregnancy have an increased incidence of genital
      abnormalities and a possibly increased risk of prostate and testicular cancer.
      Routine prostate cancer screening and testicular self-examination should be
      encouraged.

PMID- 15168960
TI  - Information from your family doctor. Diethylstilbestrol.

PMID- 15168961
TI  - Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is a group of autoimmune syndromes consisting of
      demyelinating and acute axonal degenerating forms of the disease. Nerve
      conduction study helps differentiate the heterogeneous subtypes of GBS. Patients
      exhibit a progressive paralysis that reaches a plateau phase. In most patients,
      resolution is complete or near complete. Mortality from GBS most often is
      associated with dysautonomia and mechanical ventilation. GBS usually is
      associated with an antecedent infection by one of several known pathogens. Cross
      reactivity between the pathogen and the nerve tissue sets up the autoimmune
      response. Treatment consists of supportive care, ventilatory management (in about
      one third of patients), and specific therapy with intravenous immunoglobulin or
      plasmapheresis. Consultation with a neurologist is suggested.

PMID- 15168962
TI  - Screening for thyroid disease: recommendation statement.

PMID- 15168963
TI  - Which antidepressant is best to avoid sexual dysfunction?

PMID- 15168964
TI  - Routine screening for depression, alcohol problems, and domestic violence.

PMID- 15168966
TI  - Leg rash.

PMID- 15168965
TI  - Ethinyl estradiol/drospirenone (Yasmin): a newer oral contraceptive.

PMID- 15168968
TI  - Information from your family doctor. Chronic cough: causes and cures.

PMID- 15168967
TI  - Information from your family doctor. Chronic obstructive pulmonary disease.

PMID- 15168969
TI  - Information from your family doctor. Chronic bronchitis.

PMID- 15168970
TI  - Recommended childhood and adolescent immunization schedule, United States, July
      to December, 2004.

PMID- 15168971
TI  - AAFP and ACP release practice guideline on management of newly detected atrial
      fibrillation.

PMID- 15168972
TI  - SARS--experience makes one wise.

PMID- 15168973
TI  - Evaluation of myelography and computed tomography in clinically diagnosed
      patients of lumbar disc herniation.
AB  - Forty patients with dinical diagnosis of lumbar disc herniation were evaluated
      with myelography and CT scan. Myelography diagnosed lumbar disc hemiation at 59
      levels in 40 patients, while CT diagnosed disc hemiation at 64 levels. Lumbar
      disc hemiation was confirmed peroperatively in 30 out of 40 patients at 48
      levels. Myelography correctly diagnosed 43 levels out of 48 levels and thus had a
      sensitivity of 89.6 per cent. CT diagnosed all the 48 levels correctly with a
      sensitivity of 100 per cent. Thus CT is super to conventional myelography in the
      diagnosis of lumbar disc herniation. However, conventional myelography
      supplements CT examination by limiting the number of scans to the level of
      interest and thus reduces radiation exposure.

PMID- 15168974
TI  - Xanthogranulomatous cholecystitis.
AB  - Twelve cases of xanthogranulomatous cholecystitis are reported. The clinical
      presentation was similar to chronic cholecystitis. All patients had associated
      gallstones. The diagnosis was achieved at histopathological examination of the
      resected gall bladders and none had any focus of malignancy. Cholecystectomy was
      curative.

PMID- 15168975
TI  - Diagnostic evaluation of extrapulmonary tuberculosis by fine needle aspiraton
      (FNA) supplemented with AFB smear and culture.
AB  - One hundred forty-three patients, 72 males and 71 females, with extrapulmonary
      tuberculosis were aspirated and subjected to cytological (Ziehl-Neelsen stain)
      examination and culture in Lowenstein-Jensen media. Routine haematological
      examination and Mantoux test were done in all the cases, x-ray chest in 112,
      skeletal x-ray in 3 relevant cases and sputum was examined for AFB in 16 cases
      where pulmonary tuberculosis was associated/suspected with extrapulmonary
      tuberculosis. HIV status was evaluated in 51 cases and 9 (7.64%) were
      seropositive. FNA cytology in 102 cases (71.3%) had caseating epithelioid
      granulomas while smear for AFB was positive in 57 cases (39.8%). Both culture and
      smear were positive in 29 (20.2%) cases. Combining both smear and culture yielded
      positive results in 47.5% cases. It was observed that AFB positivity was higher
      in untreated patients and with HIV positive cases. Further more, the triad of
      FNAC, AFB smear and culture were cheaper, foolproof and confirmatory than
      costlier tests like TB IgG, IgM, RTPCR and BACTEC.

PMID- 15168976
TI  - Retinopathy of prematurity--screening and management.
AB  - Retinopathy of prematurty (ROP) is a relentless disease of the retina in
      premature children that in advanced cases leads to blindness. A good screening
      programme ensures early detection and timely intervention. Surgical results in
      advanced stages of ROP are very poor. Creating awareness, training of specialists
      end development of viable ROP centres is an urgent need. New research insights
      have shown promise to prevent, detect and treat ROP.

PMID- 15168977
TI  - Sinus histiocytosis of the thyroid with massive lymphadenopathy (Rosai-Dorfman
      disease).
AB  - A 63-year-old woman presented with a midline neck swelling which clinically
      appeared as goitre with bilateral cervical lymphadenopathy. Pre-operative
      investigations were suggestive of malignancy with lymph node metastasis for which
      a subtotal thyroidectomy with lymph node excision was done. But the
      histopathological examination of the operative specimen was reported as sinus
      histiocytosis of the thyroid and the cervical lymph nodes.

PMID- 15168978
TI  - Malignant fibrous histiocytoma of the spermatic cord.
AB  - Malignant fibrous histiocytoma (MFH) of the spermatic cord is rare. However,
      owing to its location it is diagnosed early and has a better prognosis. A case of
      MFH of the spermatic cord is reported in a 50-year-old male along with review of
      the literature, discussing the recommended management and prognosis of this
      condition and emphasising upon its clinical recognition since the prognosis and
      management are different from the MFH, in general.

PMID- 15168979
TI  - Oesophageal web--a case report.
AB  - A case of posterior oesophageal web in an 18-year-old girl is being presented, in
      view of its rarity. The diagnosis could be established only after thoracotomy and
      exploration of the oesophagus. The clinical profile along with possible theories
      of aetiology are discussed and a brief review of literature is made.

PMID- 15168980
TI  - Two case reports on vaginoplasty in cases of congenital absence of vagina.
AB  - McIndoe's method is one of the very popular methods of vaginoplasty. Two cases,
      with congenital absence of vagina, are reported below where vaginoplasty was done
      with skin and amniotic membrane grafting respectively, based on the above method
      and with excellent results. The method is discussed in detail.

PMID- 15168981
TI  - Obesity.

PMID- 15168983
TI  - Should the drug companies have their diagnostic clinics.

PMID- 15168982
TI  - On HIV/AIDS.

PMID- 15168984
TI  - A glimpse of some common rheumatological disorders.

PMID- 15168985
TI  - Spondylo-arthropathies.
AB  - Spondylo-arthropathies are a broad group of inflammatory diseases that primarily
      involve the axial skeleton and the sacro-iliac joints. The pattern of peripheral
      joint involvement in spondylo-arthropathies differs from rheumatoid arthritis.
      Spondylo-arthropathies are known to include several conditions like ankylosing
      spondylitis, reactive arthritis (including Reiter's syndrome), arthritis
      associated with psoriasis and inflammatory bowel disease, juvenile and also
      undifferentiated spondylo-arthropathies. The characteristic features of spondylo
      arthropathies are absence of rheumatoid factor, inflammatory low backache, sacro
      iliitis, peripheral arthritis, enthesopathy, tendency to familial aggregation and
      association with HLA-B27. ESR may be elevated and patients may exhibit anaemia of
      chronic inflammation. HLA-B27 is a useful adjunctive test. The radiologic
      interpretation is very important. Non-steroidal anti-inflammatory drugs and
      spinal exercises are the cornerstone of therapy. Intra-articular corticosteroids
      are helpful. Patients may be benefited from, sulfasalazine, methotrexate or
      azathioprine.

PMID- 15168986
TI  - Emergencies in rheumatology.
AB  - Rheumatological conditions can sometimes present as emergencies. These can occur
      due to the disease process or may be iatrogenic. Some of the important articular
      emergencies are septic arthritis, acute polyarthritis and atlanto-axial
      dislocation. Classical polyarteritis nodosa may present with massive gastro
      intestinal bleeding, intestinal perforation or acute pancreatitis. Adult
      respiratory distress syndrome, bilateral pneumonitis and diffuse alveolar
      haemorrhage due to systemic lupus erythematosus or systemic necrotising
      vasculitis and ventilatory failure due to polymyositis are some of the
      respiratory emergencies. Scleroderma is well known to cause renal crisis which
      can be fatal if not diagnosed and managed promptly. Microscopic polyangiitis and
      Wegener's granulomatosis may cause rapidly progressive renal failure.
      Cerebrovascular accident, cortical vein thrombosis, seizures and acute psychosis
      are important neurological complications of rheumatic disease. Cardiac
      emergencies include tamponade, acute myocarditis and acute myocardial infarction.
      Vision can be threatened in Behcet's disease, temporal arteritis and seronegative
      spondylarthritis. Catastrophic antiphospholipid syndrome is a devastating
      emergency. The management of above emergencies includes critical care,
      immunosuppression when indicated and withdrawal of the offending drug.
      Anticoagulants have to be used in the management of antiphospholipid syndrome. A
      good understanding of these conditions is of paramount importance for proper
      management.

PMID- 15168987
TI  - Soft tissue rheumatism.
AB  - Soft tissue rheumatism includes disorders of tendons and their sheaths,
      ligaments, bursae, joint capsules, muscles, fasciae and others. Inflammatory
      signs or systemic manifestations may be lacking in these disorders. Fibrositis,
      bursitis, tenosynovitis, myositis are some of the common types of soft tissue
      rheumatism. The disorders can be classified broadly into two groups ie, diffuse
      and local. Proper history taking and performing detailed examination are very
      important in arriving at diagnosis. Management includes pain relief by suitable
      measures. In fibromyalgia diffuse musculoskeletal pain is observed having at
      least 11 or 18 tender points involving upper and lower body bilaterally.

PMID- 15168988
TI  - Leptospirosis and Weil's disease in eastern India.
AB  - Leptospirosis is characterised by a broad spectrum of clinical manifestations
      varying from inapparent infection to fulminant fatal disease. Severe
      leptospirosis characterised by profound jaundice is referred to as Weil's
      disease. In the present study 20 patients of leptospirosis, of which 7 belonged
      to Weil's disease, were diagnosed based on the demonstration of IgM
      antileptospira antibody and supported by clinical correlation and appropriate
      biochemical markers. Overall, the male and female ratio was 17:3 and the same
      ratio for the Weil's disease was 6:1. The most common presentation involved
      fever, malaise and myalgia. Conjunctival congestion was found in 75% of the cases
      and jaundice was encountered in 90% of the cases. The prognosis of all these
      patients, including that of Weil's disease was excellent. Early recognition and
      initiation of antibiotic therapy were found to be important.

PMID- 15168989
TI  - Rheumatoid arthritis and ocular involvement.
AB  - To study the occurrence and incidence of different ocular manifestations in
      rheumatoid arthritis a random cross-sectional study was carried out among 54
      patients with active rheumatoid arthritis. The patients were examined thoroughly
      to detect any ocular disease associated with rheumatoid arthritis. Complete
      ocular examination with special emphasis on anterior segment evaluation and
      tearfilm study was done. Two-thirds of the patients examined had some kind of
      visual problem at presentation. Three patients (5.55%) had marked dry eye with
      another 20 (37.03%) having borderline tear deficiency. Two cases ( 3.70% ) of
      episcleritis were also seen. No cases of scleritis or retinopathy were found. The
      most common ocular association with rheumatoid arthritis was secondary Sjogren's
      syndrome. Other conditions include episcleritis and marginal keratitis.

PMID- 15168990
TI  - Hysteria and other related disorders.
AB  - The term 'hysteria' is not the diagnosis any more. The various presentations
      which were previously diagnosed as hysteria are discussed in this article in
      their current nomenclature. This article emphasises the core clinical features of
      each presentation, the points of differentiation between various presentations
      and the salient points for effective management.

PMID- 15168991
TI  - Chronic fatigue syndrome or myalgic encephalomyelitis in children and
      adolescents.
AB  - Chronic fatigue syndrome or myalgic encephalomyelitis in children and adolescents
      is still poorly understood. The provisional diagnostic criteria and the concept
      are depicted here. The treatment modalities and prognosis for the disease are yet
      inconsistent.

PMID- 15168992
TI  - Microbes: therapeutic targets or therapeutic tools?
AB  - Antimicrobial resistance has produced alarming situation worldwide. Use of
      antibiotics in large scale is one of the common cause for developing microbial
      resistance. Newer and newer antibiotics are coming for their use and more
      resistance problem is arising out. A complete new method of treatment by
      bacterial interference has been evolved. However, a new method of treatment has
      evolved ie, bacterial interference.

PMID- 15168993
TI  - Congenital leukaemia in neonate with Down's syndrome.

PMID- 15168994
TI  - Hyperviscosity syndrome with pulmonary involvement.
AB  - A 44-year-old male presented with dizziness, blurring of vision, unproductive
      cough, dyspnoea, heaviness of head, fever and hepatosplenomegaly along with
      reticulonodular infiltration in chest x-ray. His serum showed monoclonal IgM
      gammopathy. Peripheral blood smear, bone marrow examination and serum protein
      electrophoresis suggested it was a case of Waldenstrom's macroglobulinaemia.
      Chest x-ray and CT scan of thorax were suggestive of pulmonary involvement in the
      form of interstitial lung disease.

PMID- 15168995
TI  - Haemobilia due to a large gall bladder polyp.
AB  - A 61-year-old male presented with recurrent bouts of haematemesis and melaena for
      last 10 days. On examination, he was found anaemic and had jaundice and a mass
      felt in the right hypochondrium. He required multiple blood transfusions.
      Oesophagogastroduodenoscopic (OGD) evaluation demonstrated no lesion, no fresh
      bleeding noticed from ampulla of Vater. Ultrasonographic evaluation demonstrated
      a heterogeneous mass within the gall bladder lumen with a chink of free lumen
      between the mass and gall bladder wall and also dilated biliary tract. Laparotomy
      confirmed mass within the gall bladder lumen without any lymph node involvement
      at porta or any liver metastasis, and had dilated common bile duct.
      Cholecystectomy was carried out. The cut section of the gall bladder showed a
      polypoid mass (5.5 cm x 4 cm) projecting inside lumen having a haemorrhagic spot
      on irregular surface and which was attached with fundus of the gall bladder
      through a small stalk. Choledochotomy showed only blood clots within the duct
      choledochoduodenostomy was also done. Histopathological examination showed
      adenomatous polyp with foci of carcinoma in-situ or ly without any evidence of
      local metastasis. Follow-up was uneventful till after 11 months.

PMID- 15168996
TI  - Tuberculosis of the gall bladder.
AB  - An unusual presentation of tuberculous involvement of gall bladder in the absence
      of clinically detectable tuberculosis elsewhere is described. Tuberculosis, a
      rare lesion in the gall bladder was seen in a case associated with chronic
      cholecystitis with acute exacerbation. This organ is supposed not to be involved
      by tuberculosis due to high concentration of bile-acids in pure bile. The mode of
      spread in the present case remains speculative.

PMID- 15168997
TI  - Movement towards exclusive breastfeeding--doctors' role to lead.

PMID- 15168998
TI  - Bladder preserving approach for muscle invasive bladder cancer--role of
      mycobacterium w.
AB  - Mycobacterium w (immuvac), a new potent immunomodulator was evaluated as
      concomitant therapy in the management of muscle invasive bladder cancer along
      with external beam radiation therapy. There was no residual tumour in all the
      five patients after two months of therapy. All patients remained disease free for
      an observation period of more than 2 years.

PMID- 15168999
TI  - Efficacy and safety of cilostazol, a novel phosphodiesterase inhibitor in
      patients with intermittent claudication.
AB  - Pharmacotherapy is limited for the relief of intermittent claudication (IC), a
      common manifestation of peripheral arterial disease (PAD). Pentoxyfylline, the
      only current pharmacological therapy for IC, has been shown to have similar
      efficacy as placebo. Cilostazol, a new phosphodiesterase III (PDE III) inhibitor,
      is a potent inhibitor of platelet aggregation with vasodilatory, antithrombotic,
      antiproliferative and positive lipid-altering effects. To evaluate the efficacy
      and safety of cilostazol for the treatment of IC in Indian patients, 123 patients
      were selected from 6 centres in India. The patients, aged 58-73 years, with the
      diagnosis of stable moderate-to-severe IC received cilostazol 100/50 mg twice
      daily for a period of 12 weeks. Primary efficacy measures included initial
      claudication distance (ICD) and absolute walking distance (ACD) by treadmill
      testing and ankle-brachial index (ABI) using Doppler ultrasonography-measured
      systolic pressures. Secondary efficacy outcomes included subjective assessment of
      symptom improvement by patient and investigator and estimation of lipid values.
      Adverse events were monitored throughout the study. Laboratory investigations
      were carried out at baseline and end of study. At the end of week 12 of
      cilostazol therapy, there was a significant improvement in the raw walking
      distances (ICD and ACD). Percentage change in ICD and ACD was 46.77% and 64.5%,
      respectively, at the end of study. There was a significant increase (32.7%) in
      the ABI by the end of study period. According to patient and investigator
      assessment of symptoms, 58-60% of the subjects showed significant improvement to
      complete resolution of claudication symptoms by the end of 12 weeks of therapy.
      In addition, there was a significant increase of 20.24% in the mean plasma HDL
      cholesterol levels and a decrease of 29.55% in the mean plasma triglyceride
      concentrations by the end of study period. Headache, diarrhoea, palpitation and
      dizziness were the commonly reported adverse effects during the study. No adverse
      effect led to discontinuation of therapy. The present study suggests that
      cilostazol is an effective therapeutic option with an acceptable tolerability
      profile for the treatment of IC in patients with PAD.

PMID- 15169000
TI  - Stringlike structure formed in thin films of a lamella-forming diblock copolymer.
AB  - Thin films of a lamella-forming polystyrene-block-poly(2-vinylpyridine) diblock
      copolymer, PS-P2VP, were annealed by a tetrahydrofuran (THF) vapor treatment. The
      thin films immediately developed a multilayered lamellar structure, similar to
      those known for conventional heat treatment. However, in the case of the vapor
      treatment, the steps moved over a significantly larger distance than the case of
      the heat treatment. This process strikingly developed stringlike objects
      (strings) that appeared near the steps. The strings were found to be cylindrical
      domains of poly(2-vinylpyridine) blocks (P2VP) partitioned from P2VP lamella
      during the step motion and sandwiched by the polystyrene phase that results in
      perforating the P2VP lamella. The string formation seemed to be associated with
      the motion of the step, which was considerably faster in the vapor treatment
      process than in the heat treatment process.

PMID- 15169002
TI  - Harmonic oscillator with fluctuating damping parameter.
AB  - The multiplicative noise in the equation of motion of an underdamped harmonic
      oscillator produced by a fluctuating damping parameter has a dramatic effect on
      the average coordinate of an oscillator. Noise of a sufficiently large strength
      leads to an instability. In the presence of an external periodic force, the
      output signal shows a nonmonotonic dependence on the strength and the rate of a
      color noise (stochastic resonance). Contrary to the case of a random frequency,
      this effect exists for white noise as well.

PMID- 15169003
TI  - Curvature-induced defect unbinding in toroidal geometries.
AB  - Toroidal templates such as vesicles with hexatic bond orientational order are
      discussed. The total energy including disclination charges is explicitly computed
      for hexatic order embedded in a toroidal geometry. Related results apply for tilt
      or nematic order on the torus in the one Frank constant approximation. Although
      there is no topological necessity for defects in the ground state, we find that
      excess disclination defects are nevertheless energetically favored for fat torii
      or moderate vesicle sizes. Some experimental consequences are discussed.

PMID- 15169004
TI  - Nonequilibrium orientational patterns in two-component Langmuir monolayers.
AB  - A model of a phase-separating two-component Langmuir monolayer in the presence of
      a photoinduced reaction interconverting two components is formulated. An
      interplay between phase separation, orientational ordering, and reaction is found
      to lead to a variety of nonequilibrium self-organized patterns, both stationary
      and traveling. Examples of the patterns, observed in numerical simulations,
      include flowing droplets, traveling stripes, wave sources, and vortex defects.

PMID- 15169001
TI  - Diffuse scattering provides material parameters and electron density profiles of
      biomembranes.
AB  - Fully hydrated stacks of DOPC lipid bilayer membranes generate large diffuse x
      ray scattering that corrupts the Bragg peak intensities that are used in
      conventional biophysical structural analysis, but the diffuse scattering actually
      contains more information. Using an efficient algorithm for fitting extensive
      regions of diffuse data to classical smectic liquid crystalline theory we first
      obtain the compressional modulus B= 10(13) erg/ cm(4), which involves
      interactions between membranes, and the bending modulus K(c) =8x 10(-13) erg of
      the membranes. The membrane form factor F ( q(z) ) is then obtained for most
      values of q(z) up to 0.8 A(-1). The electron density profile rho(z) is obtained
      by fitting models to F( q(z) ). Constraining the models to conform to other
      measurements provides structural quantities such as area A=72.1+/-0.5 A(2) per
      lipid at the interface.

PMID- 15169005
TI  - Potential-energy-landscape-based extended van der Waals equation.
AB  - The inherent structures (IS) are the local minima of the 3N-dimensional potential
      energy surface, or landscape, of an N-atom system. Stillinger has given an exact
      IS formulation of thermodynamics. Here the implications for the equation of state
      are investigated. It is shown that the van der Waals (vdW) equation, with density
      dependent a and b coefficients, holds if the averaged IS energy is close to its
      high-temperature plateau value. The density-dependence alone significantly
      enriches the equation of state. Furthermore, an additional "landscape"
      contribution to the pressure is found at lower T. The resulting extended vdW
      equation is capable of yielding a waterlike density anomaly, flat isotherms in
      the coexistence region vs vdW loops, and several other desirable features. The
      plateau IS energy, the width of the distribution of IS, and T(TOL), the "top of
      the landscape" temperature at which the plateau is reached, are simulated over a
      broad reduced density range, 2.0>or=rho>or=0.20, in the Lennard-Jones fluid. Fits
      to the data yield an explicit equation of state, which is argued to be plausible
      at high density. Nevertheless, a(rho(c)) and b(rho(c)), where rho(c) is the
      critical density, are in excellent agreement with the standard values obtained by
      fitting the vdW equation at the critical point.

PMID- 15169006
TI  - Average trajectory of returning walks.
AB  - We compute the average shape of trajectories of some one-dimensional stochastic
      processes x(t) in the (t,x) plane during an excursion, i.e., between two
      successive returns to a reference value, finding that it obeys a scaling form.
      For uncorrelated random walks the average shape is semicircular, independent from
      the single increments distribution, as long as it is symmetric. Such universality
      extends to biased random walks and Levy flights, with the exception of a
      particular class of biased Levy flights. Adding a linear damping term destroys
      scaling and leads asymptotically to flat excursions. The introduction of short
      and long ranged noise correlations induces nontrivial asymmetric shapes, which
      are studied numerically.

PMID- 15169007
TI  - Optimal paths and the calculation of state selection probabilities.
AB  - The addition of noise to a dynamical system means that initial states near points
      of instability may no longer decay to a unique stable state. A common example of
      this behavior occurs in a dynamical system with two degrees of freedom and with
      two or more stable states. If the initial state of the system is near the
      separatrices bounding the basins of attraction of these stable states, then the
      addition of noise to the system means that there is a nonzero probability that
      the stable state selected is in a different basin of attraction to that of the
      initial state. We discuss a method of calculating these state-selection
      probabilities based on a path-integral representation of the stochastic dynamics.
      The relationship of this approach to a method based on the solution of the
      backward Fokker-Planck equation is particularly stressed, since this was used in
      previous studies of problems of this type. However, while the method based on the
      backward Fokker-Planck equation is a powerful one for systems with one degree of
      freedom, in systems with more degrees of freedom it is much less useful. Since
      the standard method of solution in this case involves a series of mappings onto a
      deterministic dynamics which is simply the classical dynamics associated with the
      path-integral formulation, we argue that for systems with more than one degree of
      freedom, the path-integral method is a very natural way of calculating state
      selection probabilities. We illustrate this on a simple example taken from
      population biology, and find that the state-selection probabilities are in
      excellent agreement with Monte Carlo simulations.

PMID- 15169008
TI  - Quasisymplectic integrators for stochastic differential equations.
AB  - Two specialized algorithms for the numerical integration of the equations of
      motion of a Brownian walker obeying detailed balance are introduced. The
      algorithms become symplectic in the appropriate limits and reproduce the
      equilibrium distributions to some higher order in the integration time step.
      Comparisons with other existing integration schemes are carried out both for
      static and dynamical quantities.

PMID- 15169009
TI  - Density functional study of the phase behavior of asymmetric binary dipolar
      mixtures.
AB  - Using density functional theory in the modified mean-field (MMF) approximation we
      study the phase behavior of asymmetric binary mixtures of equisized dipolar hard
      spheres with different dipole moments in the fluid phase regime. We focus on
      "dipole-dominated" systems where isotropic attractive interactions are absent.
      Despite these restrictions our results reveal complex fluid-fluid phase behavior
      involving demixing and first- and second-order isotropic-to-ferroelectric phase
      transitions the relative importance of which depends on two "tuning" parameters,
      that is, the parameter Gamma measuring the ratio of the dipolar coupling
      strengths, and the chemical potential difference Deltamu controlling the
      composition. The interplay of these effects then yields three different types of
      phase behavior differing in the degree to which demixing dominates the system. A
      generic feature of the resulting diagrams is that the isotropic-to-ferroelectric
      transition is shifted towards significantly higher densities compared to the one
      component case, and is therefore destabilized. Furthermore, demixing in the MMF
      approach turns out to be always accompanied by spontaneous ferroelectricity,
      which is in contrast to recent integral equation and simulation results for the
      limiting case of a mixture of dipolar and pure hard spheres (Gamma=0).

PMID- 15169010
TI  - Mean-field theory, mode-coupling theory, and the onset temperature in supercooled
      liquids.
AB  - We consider the relationship between the temperature at which averaged energy
      landscape properties change sharply (T(o)) and the breakdown of mean-field
      treatments of the dynamics of supercooled liquids. First, we show that the
      solution of the wave vector dependent mode-coupling equations undergoes an
      ergodic-nonergodic transition consistently close to T(o). Generalizing the
      landscape concept to include hard-sphere systems, we show that the property of
      inherent structures that changes near T(o) is governed more fundamentally by
      packing and free volume than potential energy. Lastly, we study the finite-size
      random orthogonal model (ROM), and show that the onset of noticeable corrections
      to mean-field behavior occurs at T(o). These results highlight connections
      between the energy landscape and mode-coupling approach to supercooled liquids,
      and identify which features of the relaxation of supercooled liquids are properly
      captured by mode-coupling theory.

PMID- 15169011
TI  - Clustering in a one-dimensional inelastic lattice gas.
AB  - We analyze a lattice model closely related to the one-dimensional inelastic gas
      with periodic boundary condition. The one-dimensional inelastic gas tends to form
      high density clusters of particles with almost the same velocity, separated by
      regions of low density; plotted as a function of particle indices, the velocities
      of the gas particles exhibit sharp gradients, which we call shocks. Shocks and
      clusters are seen to form in the lattice model too, although no true positions of
      the particles are taken into account. The locations of the shocks in terms of the
      particle index show remarkable independence on the coefficient of restitution and
      the sequence of collisions used to update the system, but they do depend on the
      initial configuration of the particle velocities. We explain the microscopic
      origin of the shocks. We show that dynamics of the velocity profile inside a
      cluster satisfies a simple continuum equation, thereby allowing us to study
      cluster-cluster interactions at late times.

PMID- 15169013
TI  - Ordering of agarose near the macroscopic gelation point.
AB  - Gel formation and spatial structure is an important area of study in polymer
      physics and in macromolecular and cellular biophysics. Agarose has a sufficiently
      complex gelation mechanism to make it an interesting prototype for many other
      gelling systems, including those involved in amyloid fibrillogenesis. Static
      (over a scattering vector range of 0.1-30 microm(-1)) and dynamic light
      scattering and rheology methods were used to follow the gelation kinetics of
      agarose at 0.5% in water or in the presence of 25 mM NaCl and quenched to
      temperatures of 20-43 degrees C. Light scattering results on gelling samples are
      fully described by a fractal aggregate model with four physically meaningful
      parameters. In all cases aggregates, with fractal dimensions at or near 3, form
      more rapidly and are smaller in characteristic size at lower quench temperatures.
      A region three to four times larger than the aggregate becomes depleted of
      agarose as the gelation proceeds. Below about 30 degrees C the aggregation
      process freezes spatial ordering rapidly, resulting in fragile macroscopic gels
      as determined by rheology. Salt effects are seen to be minimal and not important
      in the fundamental aggregation mechanism.

PMID- 15169012
TI  - NMR experiments on a three-dimensional vibrofluidized granular medium.
AB  - A three-dimensional granular system fluidized by vertical container vibrations
      was studied using pulsed field gradient NMR coupled with one-dimensional magnetic
      resonance imaging. The system consisted of mustard seeds vibrated vertically at
      50 Hz, and the number of layers N(l)<or=4 was sufficiently low to achieve a
      nearly time-independent granular fluid. Using NMR, the vertical profiles of
      density and granular temperature were directly measured, along with the
      distributions of vertical and horizontal grain velocities. The velocity
      distributions showed modest deviations from Maxwell-Boltzmann statistics, except
      for the vertical velocity distribution near the sample bottom, which was highly
      skewed and non-Gaussian. Data taken for three values of N(l) and two
      dimensionless accelerations Gamma=15,18 were fitted to a hydrodynamic theory,
      which successfully models the density and temperature profiles away from the
      vibrating container bottom. A temperature inversion near the free upper surface
      is observed, in agreement with predictions based on the hydrodynamic parameter
      micro which is nonzero only in inelastic systems.

PMID- 15169014
TI  - Theory of one-dimensional swelling dynamics of polymer gels under mechanical
      constraint.
AB  - Recently, the swelling kinetics of thin-plate gels with rectangular surfaces
      under mechanical constraint was experimentally investigated [J. Chem. Phys. 114,
      5012 (2001)]]. In this system, the top and bottom surfaces of gels were
      chemically clamped on the glass plates, and the gels could swell and shrink only
      along the thickness direction when the osmotic pressure of the solvent is
      changed. Here, we analyze this process using the linearized stress-diffusion
      coupling model of gels based on the two fluids model. The result is somewhat
      unusual in that the time evolution of the thickness is described by a single
      exponential even though the swelling is governed by the diffusion of solvent.
      This result and that the characteristic relaxation time depends on the lengths of
      the rectangular surfaces and not on the thickness of gels agree well with the
      experiment.

PMID- 15169015
TI  - Dynamics of two-dimensional colloids on a disordered substrate.
AB  - Using Langevin simulations, we numerically study the dynamics of two-dimensional
      colloids on a disordered substrate. With a decreasing strength of the interaction
      between colloids, we find a crossover from elastic to plastic depinnings, where a
      substantial increase in the depinning force is observed. Furthermore, we find a
      dynamical phase transition from the moving liquid to the moving smectic at high
      driving forces by decreasing the temperature. Peak effect occurs in the dynamical
      critical driving force across the transition, accompanied by a clear crossing of
      velocity-force dependence curves.

PMID- 15169016
TI  - Depletion force between two large spheres suspended in a bath of small spheres:
      onset of the Derjaguin limit.
AB  - We analyze the depletion interaction between two hard colloids in a hard-sphere
      solvent and pay special attention to the limit of large size ratio between
      colloids and solvent particles which is governed by the well-known Derjaguin
      approximation. For separations between the colloids of less than the diameter of
      the solvent particles (defining the depletion region), the solvent structure
      between the colloids can be analyzed in terms of an effective two-dimensional
      gas. Thereby we find that the Derjaguin limit is approached more slowly than
      previously thought. This analysis is in good agreement with simulation data which
      are available for a moderate size ratio of 10. Small discrepancies in results
      from density functional theory (DFT) at this size ratio become amplified for
      larger size ratios. Therefore we have improved upon previous DFT techniques by
      imposing test-particle consistency which connects DFT to integral equations.
      However, the improved results show no convergence towards the Derjaguin limit and
      thus we conclude that this implementation of DFT together with previous ones
      which rely on test-particle insertion become unreliable in predicting the force
      in the depletion region for size ratios larger than 10.

PMID- 15169017
TI  - Directional locking effects and dynamics for particles driven through a colloidal
      lattice.
AB  - We examine the dynamics of a single colloidal particle driven through a colloidal
      lattice which can distort in response to the driven particle. We find a
      remarkably rich variety of dynamical locking phenomena as we vary the angle of
      the applied drive with respect to the orientation of the colloidal lattice. When
      the driven colloid locks to certain lattice symmetry directions, its motion is
      not necessarily aligned with the drive. Applying a transverse force to the driven
      particle can result in either increased or decreased drag in the driving
      direction, depending on the angle of the drive. The dynamical locking produces
      anomalies in both the longitudinal and the transverse velocity vs driving force
      curves, including steps and regimes of negative differential resistance. As the
      interaction of the driven particle with the surrounding lattice increases,
      significant distortion or dislocations in the surrounding media occur, and as a
      result the directional locking is enhanced. We compare these results to those
      obtained for driving particles over fixed substrates, and show that a far richer
      variety of behaviors occurs when the underlying lattice is allowed to distort. We
      discuss how this system can be used for particle species segregation when the
      onset of different locking angles occurs at different drives for varied particle
      charges. We also show that the most pronounced locking phases should be
      observable at temperatures up to the melting transition of the colloidal lattice.

PMID- 15169018
TI  - Rotational dynamics of semiflexible paramagnetic particle chains.
AB  - Paramagnetic particles have the unique ability to reversibly form magnetic
      chains. We have taken advantage of this property by permanently linking the
      chains with three linking chemistries to create flexible chains whose behavior
      changes with the application of a magnetic field. We study the behavior of these
      chains in a rotating magnetic field and model them as elastic rods. Rigid chains
      rotate as a solid body while flexible chains deform under the influence of
      magnetic, viscous, and elastic stresses. We find that the shapes chains assume in
      rotating magnetic fields confirm the chain flexibility determined from previous
      micromechanics measurements.

PMID- 15169020
TI  - Glass transition in a simple stochastic model with back-reaction.
AB  - We formulate and solve a model of dynamical arrest in colloids. A particle is
      coupled to the bath of statistically identical particles. The dynamics is
      described by Langevin equation with stochastic external force described by
      telegraphic noise. The interaction with the bath is taken into account self
      consistently through the back-reaction mechanism. Dynamically induced glass
      transition occurs for certain value of the coupling strength. Edwards-Anderson
      parameter jumps discontinuously at the transition. Another order parameter can be
      also defined, which vanishes continuously with exponent 1/2 at the critical
      point. Nonlinear response to harmonic perturbation is found.

PMID- 15169019
TI  - Thermodynamic model of electric-field-induced pattern formation in binary
      dielectric fluids.
AB  - An electric-field-induced phase transition and pattern formation in a binary
      dielectric fluid layer are studied using a coarse-grained free-energy functional.
      The electrostatic part of the free energy is a nonlinear functional of the
      dielectric function, which depends in turn on the local colloidal concentration.
      We determine the phase coexistence curve and find that beyond a critical electric
      field the system phase separates. Accompanying the phase separation are patterns
      similar to those observed in a spinodal decomposition of an ordinary binary
      fluid. The temporal evolution of the phase separating patterns are discussed both
      analytically and numerically by integrating a Cahn-Hilliard type of equation.

PMID- 15169021
TI  - Free energy and configurational entropy of liquid silica: fragile-to-strong
      crossover and polyamorphism.
AB  - Recent molecular dynamics (MD) simulations of liquid silica, using the "BKS"
      model [Phys. Rev. Lett. 64, 1955 (1990)]], have demonstrated that the liquid
      undergoes a dynamical crossover from super-Arrhenius, or "fragile" behavior, to
      Arrhenius, or "strong" behavior, as temperature T is decreased. From extensive MD
      simulations, we show that this fragile-to-strong crossover (FSC) can be connected
      to changes in the properties of the potential energy landscape, or surface (PES),
      of the liquid. To achieve this, we use thermodynamic integration to evaluate the
      absolute free energy of the liquid over a wide range of density and T. We use
      this free energy data, along with the concept of "inherent structures" of the
      PES, to evaluate the absolute configurational entropy S(c) of the liquid. We find
      that the temperature dependence of the diffusion coefficient and of S(c) are
      consistent with the prediction of Adam and Gibbs, including in the region where
      we observe the FSC to occur. We find that the FSC is related to a change in the
      properties of the PES explored by the liquid, specifically an inflection in the T
      dependence of the average inherent structure energy. In addition, we find that
      the high T behavior of S(c) suggests that the liquid entropy might approach zero
      at finite T, behavior associated with the so-called Kauzmann paradox. However, we
      find that the change in the PES that underlies the FSC is associated with a
      change in the T dependence of S(c) that elucidates how the Kauzmann paradox is
      avoided in this system. Finally, we also explore the relation of the observed PES
      changes to the recently discussed possibility that BKS silica exhibits a liquid
      liquid phase transition, a behavior that has been proposed to underlie the
      observed polyamorphism of amorphous solid silica.

PMID- 15169022
TI  - Shear-induced grain boundary motion for lamellar phases in the weakly nonlinear
      regime.
AB  - We study the effect of an externally imposed oscillatory shear on the motion of a
      grain boundary that separates differently oriented domains of the lamellar phase
      of a diblock copolymer. A direct numerical solution of the Swift-Hohenberg
      equation in shear flow is used for the case of a transverse/parallel grain
      boundary in the limits of weak nonlinearity and low shear frequency. We focus on
      the region of parameters in which both transverse and parallel lamellae are
      linearly stable. Shearing leads to excess free energy in the transverse region
      relative to the parallel region, which is in turn dissipated by net motion of the
      boundary toward the transverse region. The observed boundary motion is a
      combination of rigid advection by the flow and order parameter diffusion. The
      latter includes break up and reconnection of lamellae, as well as a weak Eckhaus
      instability in the boundary region for sufficiently large strain amplitude that
      leads to slow wave number readjustment. The net average velocity is seen to
      increase with frequency and strain amplitude, and can be obtained by a multiple
      scale expansion of the governing equations.

PMID- 15169023
TI  - Late stage kinetics for various wicking and spreading problems.
AB  - The kinetics of spreading of a liquid drop in a wedge or V-shaped groove, in a
      network of such grooves, and on a hydrophilic strip, is reexamined. The length of
      a droplet of volume Omega spreading in a wedge after a time t is predicted to
      scale as Omega(1/5) t(2/5), and the height profile is predicted to be a parabola
      in the distance along the wedge. If the droplet is spreading radially in a sparse
      network of V-shaped grooves on a surface, the radius is predicted to scale as
      Omega(1/6) t(1/3), provided the liquid is completely contained within the
      grooves. A number of other results are also obtained.

PMID- 15169024
TI  - Kinetic complete wetting of a planar defect close to a bulk tricritical point.
AB  - The nucleation of a new phase at a moving planar defect is considered in the high
      symmetry phase of a bulk tricritical point. In the first-order regime a kinetic
      complete-wetting transition is found where the thickness of the nucleation layer
      diverges, inducing a change of the drag coefficient of the defect. When the
      tricritical point is approached, the complete-wetting transition disappears, and,
      in the adjacent second-order regime, the layer thickness is finite in the full
      nucleation region.

PMID- 15169025
TI  - Influence of self-affine roughness on Parsons-Zobel plots for electrical double
      layers.
AB  - In this paper we investigate the dependence of Parsons-Zobel plots on
      characteristic self-affine roughness parameters of the metal electrode in
      electrical double layers. Among the roughness amplitude w, the correlation length
      xi, and roughness exponent H, the latter appears to have the most prominent
      effect especially for values in the range H<0.5. In addition, with decreasing
      compact layer thickness the influence of roughness leads to stronger nonlinear
      behavior of the plots for relatively large electrode potentials. Finally, it is
      shown that dynamic changes of the electrode roughness (for example by growth on
      metal films) should be carefully quantified with respect to their influence on
      the Parson-Zobel plots and related double-layer systems.

PMID- 15169026
TI  - Growth model with disaggregation of islands having an odd number of particles.
AB  - A simple model of deposition of particles and growth of point islands in a two
      dimensional substrate is introduced and studied. The detachment of particles from
      islands with an odd number of particles can occur with a probability P. The power
      law scalings of the island, monomer, and odd island densities are analytically
      obtained and verified by Monte Carlo simulations. The universality class of the
      model depends on P, and the island density exponent chi changes from chi=1/3 (for
      P=0 ) to chi=0 (for P>0 ).

PMID- 15169027
TI  - Saddle-splay-term-induced orientational instability in nematic-liquid-crystal
      cells and director fluctuations at substrates.
AB  - We analyze stability of the planar orientational structure in a nematic-liquid
      crystal cell with planar anchoring conditions at both substrates. Specifically,
      we study the instabilities of the ground state caused by surface elasticity with
      the saddle-splay elastic constant K24 violating the Ericksen inequalities. We
      express the surface part of static correlation functions as a functional integral
      over the fluctuation field induced by director fluctuations at confining walls
      and derive the stability conditions for the planar structure with respect to the
      fluctuation modes characterized by the in-plane wave numbers and by the parity.
      These conditions are analyzed in the cell thickness-fluctuation wavelength plane
      through the parametrization for the boundary curve of the instability region. For
      relatively small K24, the fluctuation mode of the critical wavelength is found to
      render the structure unstable when the thickness of the cell is below its
      critical value. The parity of the critical mode changes as the twist-splay ratio
      K(2)/K(1) is passing through unity. Further increase of K24 beyond the second
      threshold value, 4K(1)K(2)/(K1+K2), leads to the instability with respect to
      short wavelength fluctuations regardless of the cell thickness. We compute the
      critical thickness and the critical wavelength as a function of K24, the twist
      splay ratio, and the azimuthal anchoring strength.

PMID- 15169028
TI  - Experimental investigations of one liquid-crystal compound exhibiting the no
      layer-shrinkage effect near the Sm-A-Sm- C(*) transition.
AB  - Three experimental probes have been employed to investigate the nature of the
      smectic- A -smectic- C ( Sm-A-Sm- C(*) ) phase transition of one liquid-crystal
      compound showing almost no layer-shrinkage effect through the transition. Results
      from both x-ray diffraction and optical studies indicate that the compound
      exhibits a crossover behavior of different molecular packing arrangements within
      the bulk Sm-A phase window. The calorimetry results show a significant critical
      anomaly near the Sm-A-Sm- C(*) transition, although it was found to be weakly
      first order.

PMID- 15169029
TI  - Isotropic-nematic transition in hard-rod fluids: relation between continuous and
      restricted-orientation models.
AB  - We explore models of hard-rod fluids with a finite number of allowed
      orientations, and construct their bulk phase diagrams within Onsager's second
      virial theory. For a one-component fluid, we show that the discretization of the
      orientations leads to the existence of an artificial (almost) perfectly aligned
      nematic phase, which coexists with the (physical) nematic phase if the number of
      orientations is sufficiently large, or with the isotropic phase if the number of
      orientations is small. Its appearance correlates with the accuracy of sampling
      the nematic orientation distribution within its typical opening angle. For a
      binary mixture this artificial phase also exists, and a much larger number of
      orientations is required to shift it to such high densities that it does not
      interfere with the physical part of the phase diagram.

PMID- 15169030
TI  - Controlling disorder in liquid crystal aerosil dispersions.
AB  - The effect of disorder in the behavior of liquid crystal (LC) is assessed and
      controlled by dispersing known amounts of silica aerosil in the liquid crystal
      material. Using deuteron nuclear magnetic resonance, the director configuration
      and the orientational order was determined for hydrophilic aerosil dispersions in
      octylcyanobiphenyl. The confined liquid crystal exhibits a well-defined alignment
      as the silica spheres stabilize the molecular configuration. At low silica
      densities, a silica network is eventually established, forming a soft gel. When
      the sample orientation in the magnetic field is changed, a few silica strands
      links are broken and a fraction of the LC molecules is realigned. The field
      anneals the random disorder introduced by the aerosil up to a certain density
      beyond which, in the so-called stiff-gel regime, disordering effects completely
      dominate. At a fixed temperature in the isotropic phase, there is surface-induced
      order that is linearly proportional to the silica density.

PMID- 15169031
TI  - Bistable nematic and smectic anchoring in the liquid crystal octylcyanobiphenyl
      (8CB) adsorbed on a MoS2 single crystal.
AB  - We have studied the anchoring directions imposed on 4-n-octyl-4(')-cyanobiphenyl
      (8CB) smectic-A and nematic phases by a single crystal of molybdenum disulfide
      (MoS2). Combining optical microscopy and x-ray diffraction under grazing
      incidence we have demonstrated the occurrence of a bistable planar anchoring. A
      previous study of the two-dimensional (2D) network of adsorbed 8CB molecules
      under the liquid crystal film allows a direct connection to be made between the
      interface structure and the anchoring directions, demonstrating that bistability
      is induced by the presence of two dipolar groups in the skeleton of the 2D
      network. It is demonstrated that the Landau-de Gennes theory cannot account for
      the observed anchoring in the nematic phase. The Landau-de Gennes free energy has
      to be associated with a coupling with both the surface order and the MoS2
      substrate to explain the experimental observations. The hypothesis of a nematic
      layer under the liquid crystal bulk is postulated in the smectic phase.

PMID- 15169032
TI  - Interaction between two spherical particles in a nematic liquid crystal.
AB  - We numerically investigate the interaction between two spherical particles in a
      nematic liquid crystal mediated by elastic distortions in the orientational
      order. We pay attention to the cases where two particles with equal radii R0
      impose rigid normal anchoring on their surfaces and carry a pointlike topological
      defect referred to as a hyperbolic hedgehog. To describe the geometry of our
      system, we use bispherical coordinates, which prove useful in the implementation
      of boundary conditions at the particle surfaces and at infinity. We adopt the
      Landau-de Gennes continuum theory in terms of a second-rank tensor order
      parameter Q(ij) for the description of the orientational order of a nematic
      liquid crystal. We also utilize an adaptive mesh refinement scheme that has
      proven to be an efficient way of dealing with topological defects whose core size
      is much smaller than the particle size. When the two "dipoles," composed of a
      particle and a hyperbolic hedgehog, are in parallel directions, the two-particle
      interaction potential is attractive for large interparticle distances D and
      proportional to D-3 as expected from the form of the dipole-dipole interaction,
      until the well-defined potential minimum at D approximately 2.46 R0 is reached.
      For the antiparallel configuration with no hedgehogs between the two particles,
      the interaction potential is repulsive and behaves as D-2 for D less than or
      approximately equal 10R0, which is stronger than the dipole-dipole repulsion
      (approximately D-3 ) expected theoretically as an asymptotic behavior for large
      D.

PMID- 15169034
TI  - Micellar anisometry in lyotropic uniaxial nematic phases studied by transversal
      NMR relaxation dispersion.
AB  - A new method, based on the measurement of the (23 )( )Na nuclei spin-spin NMR
      relaxation times ( T2 ), is proposed to investigate the shape of micelles in
      lyotropic nematic phases. We investigate the ternary lyotropic mixture of sodium
      dodecyl sulfate, 1-decanol, and water by using the NMR technique, measuring T2 in
      the two lyotropic uniaxial nematic phases. The characteristic relaxation time
      curves of each particular phase are analyzed by considering that they are
      constituted by a superposition of exponential decays with typical characteristic
      times: in a sense, a T2 spectroscopy. The analysis of the T2 dispersion profiles
      in both the uniaxial nematic calamitic and discotic phases indicates that our
      results can be interpreted in terms of the model of intrinsically biaxial
      micelles in all the nematic phases.

PMID- 15169035
TI  - Interaction between irreversibly adsorbed polymer layers: Is the mean field
      picture really inadequate?
AB  - We found out that the mean-field theory (MFT), if done consistently, is in good
      agreement with experimental observations for the force between irreversibly
      adsorbed polymer layers. This result is fairly unexpected in light of the
      conventional Cahn-de Gennes mean-field (CdGMF) theory that claims this force is
      zero. We reexamine the CdGMF equations and show that the consistency of the CdGMF
      approach is broken. This motivated us to derive an equation for the polymer
      density on the adsorbing surface that describes a minimum of the surface free
      energy. This equation replaces the conventional boundary condition used in CdGMF.
      The disjoining pressure is calculated by making use of the developed theory. An
      excellent agreement with the experimental results is indicated. We believe that
      our findings rehabilitate the mean-field theory as one of the most powerful tools
      for investigating the polymer-mediated interaction between colloids. Our result
      show that the unphysical predictions of CdGMF are due to its inconsistency rather
      than because this approach is "completely inadequate to discuss the plate-plate
      interactions in good solvent" [Macromolecules 15, 492 (1982)]].

PMID- 15169036
TI  - Effects of temperature and pressure on the stability and mobility of phases in
      rigid rod poly (p-phenylenes).
AB  - The structure and the associated dynamics have been investigated in melts of
      hairy-rod macromolecules composed from a poly(p-phenylene) backbone with
      sulfonate ester and dodecyl side chains. For the structure investigation,
      polarizing optical microscopy, differential scanning calorimetry, pressure-volume
      temperature, and wide-angle x-ray scattering have been employed whereas for the
      dynamics dielectric spectroscopy as a function of temperature and pressure was
      used. Based on the combined information from structure and dynamics the
      relaxation mechanisms were identified and the origin of the glass transition has
      been discussed in terms of insufficient thermal energy rather than insufficient
      free volume. The relevant phase diagram has been constructed and the stability
      and mobility of phases is discussed.

PMID- 15169037
TI  - Fields and forces acting on a planar membrane with a conducting channel.
AB  - Modeling electric fields and forces around a channel in a planar membrane is
      still an open problem. Until now, most of the existing theories have
      oversimplified the electric field distribution by placing the electrode directly
      at the entry of the channel. However, in any relevant experimental setup the
      electrodes are placed far away in the electrolyte solution. We demonstrate that
      long-range deformation of the electric field distribution appears around the
      membrane, spanning on distances of the order of the distance between the membrane
      and the electrode. The forces acting due to this distribution are in most of the
      cases negligible. They can be important for channels with radii of the order of
      the thickness of the layer of structured water at the oil-water interface.

PMID- 15169033
TI  - Line tension vector thermodynamics of anisotropic contact lines.
AB  - Multiphase materials with intersecting diving surfaces give rise to contact
      lines. A line tension vector thermodynamics formalism is developed and used to
      analyze contact line problems in the presence of anisotropy, taking into account
      two elastic modes: change in contact line length and change in contact line
      orientation. Using this formalism, the contact line-shape equation is derived,
      and the renormalization of the line tension due to anisotropy is characterized.
      The correspondence and analogies between the shape equation for anisotropic
      surfaces (Herring equation) and the shape equation for contact lines is
      established. Line energies for nematic liquid crystals, representative of generic
      anisotropic contact lines, are used to derive a shape equation that takes into
      account ambient orientation effects. It is found that anisotropic line tension
      may promote bending and chiral modes to avoid unfavorable orientations of the
      contact line with respect to the ambient nematic ordering.

PMID- 15169038
TI  - Transcription rate of RNA polymerase under rotary torque.
AB  - We investigated the transcription rates of RNA polymerases that were subjected to
      rotational drag. By combining chemical kinetics with mechanical equations, we
      derived formulas for the transcription rate in the case where the torque was
      caused by the hydrodynamic drag to DNA rotation.

PMID- 15169039
TI  - Thermodynamic modeling of donor splice site recognition in pre-mRNA.
AB  - When eukaryotic genes are edited by the spliceosome, the first step in intron
      recognition is the binding of a U1 small nuclear RNA with the donor ( 5(') )
      splice site. We model this interaction thermodynamically to identify splice
      sites. Applied to a set of 65 annotated genes, our "finding with binding" method
      achieves a significant separation between real and false sites. Analyzing binding
      patterns allows us to discard a large number of decoy sites. Our results improve
      statistics-based methods for donor site recognition, demonstrating the promise of
      physical modeling to find functional elements in the genome.

PMID- 15169040
TI  - Attraction between DNA molecules mediated by multivalent ions.
AB  - The effective force between two parallel DNA molecules is calculated as a
      function of their mutual separation for different valencies of counterion and
      salt ions and different salt concentrations. Computer simulations of the
      primitive model are used and the shape of the DNA molecules is accurately modeled
      using different geometrical shapes. We find that multivalent ions induce a
      significant attraction between the DNA molecules whose strength can be tuned by
      the averaged valency of the ions. The physical origin of the attraction is traced
      back either to electrostatics or to entropic contributions. For multivalent
      counterions and monovalent salt ions, we find a salt-enhanced repulsion effect:
      the force is first attractive but gets repulsive with increasing salt
      concentration. Furthermore, we show that the multivalent-ion-induced attraction
      does not necessarily correlate with DNA overcharging.

PMID- 15169041
TI  - Nonlinear effects in the torsional adjustment of interacting DNA.
AB  - DNA molecules in solution, having negatively charged phosphates and
      countercations readsorbed on its surface, possess a distinct charge separation
      motif to interact electrostatically. If their double-helical structure were
      ideal, duplexes in parallel juxtaposition could choose azimuthal alignment
      providing attraction, or at least a reduction of repulsion, between them. But
      duplexes are not perfect staircases and the distortions of their helical
      structure correlate with their base pair texts. If the patterns of distortions on
      the opposing molecules are uncorrelated, the mismatch will accumulate as a random
      walk and attraction vanishes. Based on this idea, a model of recognition of
      homologous sequences has been proposed [A. A. Kornyshev and S. Leikin, Phys. Rev.
      Lett. 86, 3666 (2001)]. But DNA has torsional elasticity. How will this help to
      relax a mismatch between the charge distributions on two nonhomologous DNA's? In
      the same work, the solution of this problem has been mapped onto a frustrated
      sine Gordon equation in a nonlocal random field (where the latter represents a
      pattern of twist angle distortions on the opposing molecules), but the results
      had been obtained in the limit of torsionally rigid molecules. In the present
      paper, by solving this equation numerically, we find a strongly nonlinear
      relaxation mechanism which utilizes static kink-soliton modes triggered by the
      "random field." In the range of parameters where the solitons do not emerge, we
      find good agreement with the results of a variational study [A. G. Cherstvy, A.
      A. Kornyshev, and S. Leikin, J. Phys. Chem. B (to be published)]. We reproduce
      the first-order transitions in the interaxial separation dependence, but detect
      also second-order or weak first-order transitions for shorter duplexes. The
      recognition energy between two nonhomologous DNA sequences is calculated as a
      function of interaxial separation and the length of juxtaposition. The soliton
      caused kinky length dependence is discussed in connection with plots of
      recombination frequency as a function of the length of homology.

PMID- 15169043
TI  - Population dynamics in the Penna model.
AB  - We build upon the recent steady-state Penna model solution [J. B. Coe, Y. Mao,
      and M. E. Cates, Phys. Rev. Lett. 89, 288103 (2002)] to study the population
      dynamics within the Penna model. We show that any perturbation to the population
      can be broken into a collection of modes each of which decay exponentially with
      its respective time constant. The long time behavior of population is therefore
      likely to be dominated by the modes with the largest time constants. We confirm
      our analytical approach with simulation data.

PMID- 15169044
TI  - Discrete molecular dynamics simulations of peptide aggregation.
AB  - We study the aggregation of peptides using the discrete molecular dynamics
      simulations. Specifically, at temperatures above the alpha-helix melting
      temperature of a single peptide, the model peptides aggregate into a multilayer
      parallel beta-sheet structure. This structure has an interstrand distance of 4.8
      A and an intersheet distance of 10 A, which agree with experimental observations.
      Our model explains these results as follows: hydrogen-bond interactions give rise
      to the interstrand spacing in beta sheets, while Go interactions between side
      chains make beta strands parallel to each other and allow beta sheets to pack
      into layers. An important feature of our results is that the aggregates contain
      free edges, which may allow for further aggregation of model peptides to form
      elongated fibrils.

PMID- 15169042
TI  - Relaxation channels of two-vibron bound states in alpha-helix proteins.
AB  - Relaxation channels for two-vibron bound states in an anharmonic alpha-helix
      protein are studied. According to a recently established small polaron model [V.
      Pouthier, Phys. Rev. E 68, 021909 (2003)], it is shown that the relaxation
      originates in the interaction between the dressed anharmonic vibrons and the
      remaining phonons. This interaction is responsible for the occurrence of
      transitions between two-vibron eigenstates mediated by both phonon absorption and
      phonon emission. At biological temperature, the relaxation rate does not
      significantly depend on the nature of the two-vibron states involved in the
      process. The lifetime for both bound and free states is of the same order of
      magnitude and ranges between 0.1 and 1.0 ps for realistic parameter values. By
      contrast, the relaxation channels strongly depend on the nature of the two-vibron
      states which is a consequence of the breatherlike behavior of the two-vibron
      bound states.

PMID- 15169045
TI  - Learning in neural networks by reinforcement of irregular spiking.
AB  - Artificial neural networks are often trained by using the back propagation
      algorithm to compute the gradient of an objective function with respect to the
      synaptic strengths. For a biological neural network, such a gradient computation
      would be difficult to implement, because of the complex dynamics of intrinsic and
      synaptic conductances in neurons. Here we show that irregular spiking similar to
      that observed in biological neurons could be used as the basis for a learning
      rule that calculates a stochastic approximation to the gradient. The learning
      rule is derived based on a special class of model networks in which neurons fire
      spike trains with Poisson statistics. The learning is compatible with forms of
      synaptic dynamics such as short-term facilitation and depression. By correlating
      the fluctuations in irregular spiking with a reward signal, the learning rule
      performs stochastic gradient ascent on the expected reward. It is applied to two
      examples, learning the XOR computation and learning direction selectivity using
      depressing synapses. We also show in simulation that the learning rule is
      applicable to a network of noisy integrate-and-fire neurons.

PMID- 15169046
TI  - Analysis of the noise-induced bursting-spiking transition in a pancreatic beta
      cell model.
AB  - A stochastic model of the electrophysiological behavior of the pancreatic beta
      cell is studied, as a paradigmatic example of a bursting biological cell embedded
      in a noisy environment. The analysis is focused on the distortion that a growing
      noise causes to the basic properties of the membrane potential signals, such as
      their periodic or chaotic nature, and their bursting or spiking behavior. We
      present effective computational tools to obtain as much information as possible
      from these signals, and we suggest that the methods could be applied to real time
      series. Finally, a universal dependence of the main characteristics of the
      membrane potential on the size of the considered cell cluster is presented.

PMID- 15169048
TI  - Molecular gas dynamics observations of Chapman-Enskog behavior and departures
      there from in nonequilibrium gases.
AB  - Bird's direct simulation Monte Carlo method is used to compute the molecular
      velocity distribution of a gas with heat flow. At continuum nonequilibrium
      conditions (small heat flux), Chapman-Enskog behavior is obtained for inverse
      power-law molecules (hard-sphere through Maxwell): the Sonine-polynomial
      coefficients away from walls (i.e., the normal solution) agree with theory. At
      noncontinuum nonequilibrium conditions (large heat flux), these coefficients
      differ systematically from their continuum values as the local Knudsen number
      (nondimensional heat flux) is increased.

PMID- 15169047
TI  - From deterministic dynamics to kinetic phenomena.
AB  - We investigate a one-dimensional Hamiltonian system that describes a system of
      particles interacting through short-range repulsive potentials. Depending on the
      particle mean energy epsilon the system demonstrates a spectrum of kinetic
      regimes, characterized by their transport properties ranging from ballistic
      motion to localized oscillations through anomalous diffusion regimes. We
      establish relationships between the observed kinetic regimes and the
      "thermodynamic" states of the system. The nature of heat conduction in the
      proposed model is discussed.

PMID- 15169049
TI  - Dynamics of core-shell particles in concentrated suspensions.
AB  - The dynamics of soft colloidal particles in a concentrated suspension was studied
      by two color dynamic light scattering. The short-time diffusion coefficient,
      D(s)(q), revealed a weak slowing down around the peak of S(q) in contrast to the
      much stronger dependence observed in hard sphere systems, and the absence of any
      slowing down in ultrasoft diblock micelles. The low-q limit of the diffusion
      coefficient, D(s)(q=0), reflecting the cooperative nature of the dynamics was
      found to decrease from its dilute limit value in contrast to the weak increase
      observed in hard sphere systems. The behavior of D(s)(q) reflects distinct
      polymer-layer-induced hydrodynamic effects present in concentrated suspensions of
      core-shell particles.

PMID- 15169050
TI  - Landscape equivalent of the shoving model.
AB  - It is shown that the shoving model expression for the average relaxation time of
      viscous liquids, according to which the activation energy is proportional to the
      instantaneous shear modulus, follows largely from a classical "landscape"
      estimation of barrier heights from curvature at energy minima. Although the
      activation energy in this reasoning involves both instantaneous bulk and shear
      moduli, the bulk modulus contributes less than 8% to the temperature dependence
      of the activation energy. This reflects the fact that the physics of the two
      models are closely related.

PMID- 15169051
TI  - Contracted Fisher equation.
AB  - We apply the method of contraction, familiar in statistical mechanics
      applications, to reduce the Fisher equation describing population growth and
      dispersal in the space-time domain to an equation in the time domain. The
      resulting equation is identical to the well-known logistic equation with an
      additional correction term that depends on the global solution to the Fisher
      equation. This equation provides a possible basis for explaining why logistic
      dynamics has not always described experimental data and also for then formulating
      models that generalize the logistic equation.

PMID- 15169053
TI  - Performance of networks of artificial neurons: the role of clustering.
AB  - The performance of the Hopfield neural network model is numerically studied on
      various complex networks, such as the Watts-Strogatz network, the Barabasi-Albert
      network, and the neuronal network of Caenorhabditis elegans. Through the use of a
      systematic way of controlling the clustering coefficient, with the degree of each
      neuron kept unchanged, we find that the networks with the lower clustering
      exhibit much better performance. The results are discussed in the practical
      viewpoint of application, and the biological implications are also suggested.

PMID- 15169052
TI  - Optimum ion channel properties in the squid giant axon.
AB  - Evolutionary pressures are presumed to act so as to maximize the efficiency of
      biological systems. However, the utility of that premise is marred by the
      difficulties in defining and evaluating both the efficiency of systems and the
      character of the available variation space. Following Hodgkin and Adrian, we
      examine the character of voltage gated ion channels in the nonmyelinated giant
      axons of the squid and find that both the channel densities and channel
      transition rates have values that nearly optimize signal sensitivity as well as
      signal velocity.

PMID- 15169054
TI  - Global spatiotemporal order and induced stochastic resonance due to a locally
      applied signal.
AB  - We study the phenomenon of spatiotemporal stochastic resonance (STSR) in a chain
      of diffusively coupled bistable oscillators. In particular, we examine the
      situation in which the global STSR response is controlled by a locally applied
      signal and reveal a wave-front propagation. In order to deepen the understanding
      of the system dynamics, we introduce, on the time scale of STSR, the study of the
      effective statistical renormalization of a generic lattice system. Using this
      technique we provide a criterion for STSR, and predict and observe numerically a
      bifurcationlike behavior that reflects the difference between the most probable
      value of the local quasiequilibrium density and its mean value. Our results,
      tested with a chain of nonlinear oscillators, appear to possess some universal
      qualities and may stimulate a deeper search for more generic phenomena.

PMID- 15169055
TI  - Critical exponents of isotropic-hexatic phase transition in the hard-disk system.
AB  - The hard-disk system is studied by observing the nonequilibrium relaxation
      behavior of a bond-orientational order parameter. The density dependence of
      characteristic relaxation time tau is estimated from the finite-time scaling
      analysis. The critical point between the fluid and the hexatic phase is refined
      to be 0.899 (1) by assuming the divergence behavior of the Kosterlitz-Thouless
      transition. The value of the critical exponent eta is also studied by analyzing
      the fluctuation of the order parameter at the criticality and estimated as
      eta=0.25 (2). These results are consistent with the prediction by the Kosterlitz
      Thouless-Halperin-Nelson-Young theory.

PMID- 15169056
TI  - Model for cascading failures in complex networks.
AB  - Large but rare cascades triggered by small initial shocks are present in most of
      the infrastructure networks. Here we present a simple model for cascading
      failures based on the dynamical redistribution of the flow on the network. We
      show that the breakdown of a single node is sufficient to collapse the efficiency
      of the entire system if the node is among the ones with largest load. This is
      particularly important for real-world networks with a highly hetereogeneous
      distribution of loads as the Internet and electrical power grids.

PMID- 15169057
TI  - Numerical study of the Langevin theory for fixed-energy sandpiles.
AB  - The recently proposed Langevin equation, aimed to capture the relevant critical
      features of stochastic sandpiles and other self-organizing systems, is studied
      numerically. The equation is similar to the Reggeon field theory, describing
      generic systems with absorbing states, but it is coupled linearly to a second
      conserved and static (nondiffusive) field. It has been claimed to represent a
      different universality class, including different discrete models: the Manna as
      well as other sandpiles, reaction-diffusion systems, etc. In order to integrate
      the equation, and surpass the difficulties associated with its singular noise, we
      follow a numerical technique introduced by Dickman. Our results coincide
      remarkably well with those of discrete models claimed to belong to this
      universality class, in one, two, and three dimensions. This provides a strong
      backing for the Langevin theory of stochastic sandpiles, and to the very
      existence of this meagerly understood universality class.

PMID- 15169058
TI  - Chaotic behaviors of operational amplifiers.
AB  - We investigate nonlinear dynamical behaviors of operational amplifiers. When the
      output terminal of an operational amplifier is connected to the inverting input
      terminal, the circuit exhibits period-doubling bifurcation, chaos, and periodic
      windows, depending on the voltages of the positive and the negative power
      supplies. We study these nonlinear dynamical characteristics of this electronic
      circuit experimentally.

PMID- 15169059
TI  - Nonextensive Pesin identity: exact renormalization group analytical results for
      the dynamics at the edge of chaos of the logistic map.
AB  - We show that the dynamical and entropic properties at the chaos threshold of the
      logistic map are naturally linked through the nonextensive expressions for the
      sensitivity to initial conditions and for the entropy. We corroborate
      analytically, with the use of the Feigenbaum renormalization group
      transformation, the equality between the generalized Lyapunov coefficient
      lambda(q) and the rate of entropy production, K(q), given by the nonextensive
      statistical mechanics. Our results advocate the validity of the q -generalized
      Pesin identity at critical points of one-dimensional nonlinear dissipative maps.

PMID- 15169060
TI  - Statistical theory of high-gain free-electron laser saturation.
AB  - We propose an approach, based on statistical mechanics, to predict the saturated
      state of a single-pass, high-gain free-electron laser. In analogy with the
      violent relaxation process in self-gravitating systems and in the Euler equation
      of two-dimensional turbulence, the initial relaxation of the laser can be
      described by the statistical mechanics of an associated Vlasov equation. The
      laser field intensity and the electron bunching parameter reach a quasistationary
      value which is well fitted by a Vlasov stationary state if the number of
      electrons N is sufficiently large. Finite N effects (granularity) finally drive
      the system to Boltzmann-Gibbs statistical equilibrium, but this occurs on times
      that are unphysical (i.e., excessively long undulators). All theoretical
      predictions are successfully tested by means of finite- N numerical experiments.

PMID- 15169061
TI  - Suppression of the pulsed regimes appearing in free-electron lasers using
      feedback control of an unstable stationary state.
AB  - We show that the pulsed regimes observed in free-electron lasers (FELs) can be
      suppressed using feedback control. By applying tiny parameter perturbations, the
      feedback allows to keep the systems onto a stationary state that is naturally
      existing in phase space, but is usually inaccessible because of its unstable
      nature. We test this method numerically on a master equation derived from the
      classical iterative model. Then we present the experimental results obtained on
      the super-ACO FEL. This method is in principle directly applicable to the other
      free-electron lasers, whose instabilities have a dynamical (deterministic)
      origin.

PMID- 15169063
TI  - Lattice theory of trapping reactions with mobile species.
AB  - We present a stochastic lattice theory describing the kinetic behavior of
      trapping reactions A+B-->B, in which both the A and B particles perform an
      independent stochastic motion on a regular hypercubic lattice. Upon an encounter
      of an A particle with any of the B particles, A is annihilated with a finite
      probability; finite reaction rate is taken into account by introducing a set of
      two-state random variables--"gates," imposed on each B particle, such that an
      open (closed) gate corresponds to a reactive (passive) state. We evaluate here a
      formal expression describing the time evolution of the A particle survival
      probability, which generalizes our previous results. We prove that for quite a
      general class of random motion of the species involved in the reaction process,
      for infinite or finite number of traps, and for any time t, the A particle
      survival probability is always larger in the case when A stays immobile, than in
      situations when it moves.

PMID- 15169062
TI  - Observation of millimeter-wave radiation generated by the interaction between an
      electron beam and a photonic crystal.
AB  - We observed directional light emission in the millimeter-wave region when a high
      energy (150 MeV) electron beam passes just above a photonic crystal made of
      polytetrafluoroethylene beads ( approximately 3.2 mm in diameter). The relation
      between the momentum and the energy of the emitted photons strongly suggests that
      the observed light is generated by the umklapp scattering process that changes
      the evanescent waves emitted by the electron beam into observable ones. By
      comparing the observed spectra with calculated ones based on the photonic band
      structure, we found that generated photons excite the photonic band modes making
      them observable as enhanced fine structures in the emission spectra.

PMID- 15169064
TI  - Inelastically scattering particles and wealth distribution in an open economy.
AB  - Using the analogy with inelastic granular gases we introduce a model for wealth
      exchange in society. The dynamics is governed by a kinetic equation, which allows
      for self-similar solutions. The scaling function has a power-law tail, the
      exponent being given by a transcendental equation. In the limit of continuous
      trading, a closed form of the wealth distribution is calculated analytically.

PMID- 15169065
TI  - Hydrodynamic limit of multichain driven diffusive models.
AB  - A class of models, generalizing asymmetric exclusion process for many parallel
      interacting channels, is proposed. We couple the models with boundary reservoirs,
      study boundary-driven phase transitions, and show that usually taken hydrodynamic
      description fails. The adequate hydrodynamic limit is then derived. We support
      our findings with Monte Carlo simulations of the original stochastic system.

PMID- 15169066
TI  - Computation of the Ising partition function for two-dimensional square grids.
AB  - An improved method for obtaining the Ising partition function of n x n square
      grids with periodic boundary is presented. Our method applies results from Galois
      theory in order to split the computation into smaller parts and at the same time
      avoid the use of numerics. Using this method we have computed the exact partition
      function for the (320 x 320) grid, the ( 256 x 256 ) grid, and the ( 160 x 160 )
      grid, as well as for a number of smaller grids. We obtain scaling parameters and
      compare with what theory prescribes.

PMID- 15169067
TI  - Stationary motion of active Brownian particles.
AB  - The stationary motion of active Brownian particles is studied by using the
      stochastic averaging method for quasi-integrable Hamiltonian systems. First the
      stochastic averaging method for quasi-integrable Hamiltonian systems is briefly
      introduced. Then the stationary solution of the dynamic equations governing an
      active Brown particle in plane with the Rayleigh velocity-dependent friction
      model subject to Gaussian white noise excitations is obtained by using the
      stochastic averaging method. The solution is validated by comparison with the
      result from Monte Carlo simulation. Finally, two more stationary solutions of the
      dynamic equations governing active Brownian particle with the Schienbein-Gruler
      and Erdmann velocity-dependent friction models, respectively, subject to Gaussian
      white noise excitations are also given.

PMID- 15169068
TI  - Statistical analysis of airport network of China.
AB  - Through the study of airport network of China (ANC), composed of 128 airports
      (nodes) and 1165 flights (edges), we show the topological structure of ANC
      conveys two characteristics of small worlds, a short average path length (2.067)
      and a high degree of clustering (0.733). The cumulative degree distributions of
      both directed and undirected ANC obey two-regime power laws with different
      exponents, i.e., the so-called double Pareto law. In-degrees and out-degrees of
      each airport have positive correlations, whereas the undirected degrees of
      adjacent airports have significant linear anticorrelations. It is demonstrated
      both weekly and daily cumulative distributions of flight weights (frequencies) of
      ANC have power-law tails. Besides, the weight of any given flight is proportional
      to the degrees of both airports at the two ends of that flight. It is also shown
      the diameter of each subcluster (consisting of an airport and all those airports
      to which it is linked) is inversely proportional to its density of connectivity.
      Efficiency of ANC and of its subclusters is measured through a simple definition.
      In terms of that, the efficiency of ANC's subclusters increases as the density of
      connectivity does. ANC is found to have an efficiency of 0.484.

PMID- 15169069
TI  - Accelerated growth in outgoing links in evolving networks: deterministic versus
      stochastic picture.
AB  - In several real-world networks such as the Internet, World Wide Web, etc., the
      number of links grow in time in a nonlinear fashion. We consider growing networks
      in which the number of outgoing links is a nonlinear function of time but new
      links between older nodes are forbidden. The attachments are made using a
      preferential attachment scheme. In the deterministic picture, the number of
      outgoing links m (t) at any time t is taken as N (t)(theta) where N (t) is the
      number of nodes present at that time. The continuum theory predicts a power-law
      decay of the degree distribution: P (k) proportional to k-(1-2/ (1-theta ) ),
      while the degree of the node introduced at time t(i) is given by
      k(t(i),t)=t(theta)(i) [t/t(i) ]((1+theta)/2) when the network is evolved till
      time t. Numerical results show a growth in the degree distribution for small k
      values at any nonzero theta. In the stochastic picture, m (t) is a random
      variable. As long as <m (t) > is independent of time, the network shows a
      behavior similar to the Barabasi-Albert (BA) model. Different results are
      obtained when <m (t) > is time dependent, e.g., when m (t) follows a distribution
      P (m) proportional to m(-lambda). The behavior of P (k) changes significantly as
      lambda is varied: for lambda>3, the network has a scale-free distribution
      belonging to the BA class as predicted by the mean field theory; for smaller
      values of lambda it shows different behavior. Characteristic features of the
      clustering coefficients in both models have also been discussed.

PMID- 15169070
TI  - Effects of additive noise on vibrational resonance in a bistable system.
AB  - We study the overdamped motion of a particle in a bistable potential subject to
      the action of a bichromatic force and additive noise, within the context of the
      vibrational resonance phenomenon. Under appropriate conditions, we obtain
      analytical expressions for the relevant observables which quantifies this
      phenomenon. The theoretical results are compared with those obtained by the
      numerical solution of the stochastic differential equation which describes the
      dynamics of the system. The limits of validity of the theoretical approach are
      also discussed.

PMID- 15169072
TI  - Neural cryptography with feedback.
AB  - Neural cryptography is based on a competition between attractive and repulsive
      stochastic forces. A feedback mechanism is added to neural cryptography which
      increases the repulsive forces. Using numerical simulations and an analytic
      approach, the probability of a successful attack is calculated for different
      model parameters. Scaling laws are derived which show that feedback improves the
      security of the system. In addition, a network with feedback generates a
      pseudorandom bit sequence which can be used to encrypt and decrypt a secret
      message.

PMID- 15169071
TI  - Rate description of Fokker-Planck processes with time-dependent parameters.
AB  - The reduction of a continuous Markov process with multiple metastable states to a
      discrete rate process is investigated in the presence of slow time-dependent
      parameters such as periodic external forces or slowly fluctuating barrier
      heights. A quantitative criterion is provided under which condition a kinetic
      description with time-dependent frozen rates applies and nonadiabatic corrections
      to the frozen rates are obtained. Finally it is shown how the long-time behavior
      of the underlying continuous process can be retrieved from the knowledge of the
      discrete process by means of an appropriate random decoration of the discrete
      states. As a particular example of the presented theory an overdamped bistable
      Brownian oscillator with periodic driving is discussed.

PMID- 15169073
TI  - Improved statistical test for nonstationarity using recurrence time statistics.
AB  - We have recently introduced a measure for nonstationarity using a recurrence time
      statistic to assess stationarity. In this paper we propose an extension of this
      method based on a detailed study of the statistics for the case of stationary
      systems. We derive a simple scheme that allows us to estimate the effective
      number of degrees of freedom relevant for this statistic. This substantially
      improves the statistical significance of the method and can be used to improve
      the significance of various other nonlinear statistics.

PMID- 15169074
TI  - Stochastic cellular automata model for stock market dynamics.
AB  - In the present work we introduce a stochastic cellular automata model in order to
      simulate the dynamics of the stock market. A direct percolation method is used to
      create a hierarchy of clusters of active traders on a two-dimensional grid.
      Active traders are characterized by the decision to buy, sigma(i) (t)=+1, or
      sell, sigma(i) (t)=-1, a stock at a certain discrete time step. The remaining
      cells are inactive, sigma(i) (t)=0. The trading dynamics is then determined by
      the stochastic interaction between traders belonging to the same cluster.
      Extreme, intermittent events, such as crashes or bubbles, are triggered by a
      phase transition in the state of the bigger clusters present on the grid, where
      almost all the active traders come to share the same spin orientation. Most of
      the stylized aspects of the financial market time series, including multifractal
      proprieties, are reproduced by the model. A direct comparison is made with the
      daily closures of the S&P 500 index.

PMID- 15169075
TI  - Finite-size fluctuations in interacting particle systems.
AB  - Fluctuations may govern the fate of an interacting particle system even on the
      mean-field level. This is demonstrated via a three species cyclic trapping
      reaction with a large, yet finite number of particles, where the final number of
      particles N(f) scales logarithmically with the system size N, N(f) approximately
      ln N. Statistical fluctuations, that become significant as the number of
      particles diminishes, are responsible for this behavior. This phenomenon
      underlies a broad range of interacting particle systems including in particular
      multispecies annihilation processes.

PMID- 15169076
TI  - Kinetic phase transition in A2 + B2 -->2AB reaction system.
AB  - Three lattice gas models for A2 + B2 -->2AB reaction system are studied by Monte
      Carlo simulation in two-dimensional triangular lattice surface. When both A2 and
      B2 adsorb and dissociate on the catalytic surface in the random dimer-filling
      mechanism or in the end-on dimer-filling mechanism, there is no reactive window
      in the reaction system and just a discontinuous phase transition appears from a
      "B+vacancy" poisoned state to an "A+vacancy" poisoned state. However, a reactive
      window appears when one of the two dimers, A2, dissociates in the random dimer
      filling mechanism but another dimer, B2, is in the end-on dimer-filling mechanism
      and the system exhibits a discontinuous phase transition from the active reaction
      state to a B+ vacancy poisoned state and a continuous phase transition to an
      "A+vacancy" poisoned state. Furthermore, we show that the critical behavior of
      the continuous phase transition with infinitely many absorbing states belongs to
      the robust directed percolation universality class.

PMID- 15169077
TI  - Two-phase phenomena, minority games, and herding models.
AB  - The recently discovered two-phase phenomenon in financial markets [Nature 421,
      130 (2003)] is examined with the German financial index DAX, minority games, and
      dynamic herding models. It is observed that the two-phase phenomenon is an
      important characteristic of financial dynamics, independent of volatility
      clustering. An interacting herding model correctly produces the two-phase
      phenomenon.

PMID- 15169078
TI  - Behavior of coupled automata.
AB  - We study the nature of statistical correlations that develop between systems of
      interacting self-organized critical automata (sandpiles). Numerical and
      analytical findings are presented describing the emergence of "synchronization"
      between sandpiles and the dependency of this synchronization on factors such as
      variations in coupling strength, toppling rule probabilities, symmetric versus
      asymmetric coupling rules, and numbers of sandpiles.

PMID- 15169079
TI  - Statistical mechanics of topological phase transitions in networks.
AB  - We provide a phenomenological theory for topological transitions in restructuring
      networks. In this statistical mechanical approach energy is assigned to the
      different network topologies and temperature is used as a quantity referring to
      the level of noise during the rewiring of the edges. The associated microscopic
      dynamics satisfies the detailed balance condition and is equivalent to a lattice
      gas model on the edge-dual graph of a fully connected network. In our studies
      based on an exact enumeration method, Monte Carlo simulations, and theoretical
      considerations-we find a rich variety of topological phase transitions when the
      temperature is varied. These transitions signal singular changes in the essential
      features of the global structure of the network. Depending on the energy function
      chosen, the observed transitions can be best monitored using the order parameters
      Phi(s)=s(max)/M, i.e., the size of the largest connected component divided by the
      number of edges, or Phi(k)=k(max)/M, the largest degree in the network divided by
      the number of edges. If, for example, the energy is chosen to be E=-s(max), the
      observed transition is analogous to the percolation phase transition of random
      graphs. For this choice of the energy, the phase diagram in the (<k>,T) plane is
      constructed. Single-vertex energies of the form E= summation operator (i)f(k(i)),
      where k(i) is the degree of vertex i, are also studied. Depending on the form of
      f(k(i)), first-order and continuous phase transitions can be observed. In case of
      f(k(i))=-(k(i)+alpha)ln(k(i)), the transition is continuous, and at the critical
      temperature scale-free graphs can be recovered. Finally, by abruptly decreasing
      the temperature, nonequilibrium processes (e.g., nucleation and growth of
      particular topological phases) can also be interpreted by the present approach.

PMID- 15169080
TI  - Quantum statistical calculations and symplectic corrector algorithms.
AB  - The quantum partition function at finite temperature requires computing the trace
      of the imaginary time propagator. For numerical and Monte Carlo calculations, the
      propagator is usually split into its kinetic and potential parts. A higher-order
      splitting will result in a higher-order convergent algorithm. At imaginary time,
      the kinetic energy propagator is usually the diffusion Green's function. Since
      diffusion cannot be simulated backward in time, the splitting must maintain the
      positivity of all intermediate time steps. However, since the trace is invariant
      under similarity transformations of the propagator, one can use this freedom to
      "correct" the split propagator to higher order. This use of similarity transforms
      classically gives rise to symplectic corrector algorithms. The split propagator
      is the symplectic kernel and the similarity transformation is the corrector. This
      work proves a generalization of the Sheng-Suzuki theorem: no positive time step
      propagators with only kinetic and potential operators can be corrected beyond
      second order. Second-order forward propagators can have fourth-order traces only
      with the inclusion of an additional commutator. We give detailed derivations of
      four forward correctable second-order propagators and their minimal correctors.

PMID- 15169081
TI  - Critical Casimir force and its fluctuations in lattice spin models: exact and
      Monte Carlo results.
AB  - We present general arguments and construct a stress tensor operator for finite
      lattice spin models. The average value of this operator gives the Casimir force
      of the system close to the bulk critical temperature T(c). We verify our
      arguments via exact results for the force in the two-dimensional Ising model, d 
      dimensional Gaussian, and mean spherical model with 2<d<4. On the basis of these
      exact results and by Monte Carlo simulations for three-dimensional Ising, XY, and
      Heisenberg models we demonstrate that the standard deviation of the Casimir force
      F(C) in a slab geometry confining a critical substance in-between is k(b) TD(T)
      (A/ a(d-1) )(1/2), where A is the surface area of the plates, a is the lattice
      spacing, and D(T) is a slowly varying nonuniversal function of the temperature T.
      The numerical calculations demonstrate that at the critical temperature T(c) the
      force possesses a Gaussian distribution centered at the mean value of the force
      <F(C)> = k(b) T(c) (d-1)Delta/ (L/a)(d), where L is the distance between the
      plates and Delta is the (universal) Casimir amplitude.

PMID- 15169082
TI  - Enhanced winning in a competing population by random participation.
AB  - We study a version of the minority game in which one agent is allowed to join the
      game in a random fashion. It is shown that in the crowded regime, i.e., for small
      values of the memory size m of the agents in the population, the agent performs
      significantly well if she decides to participate the game randomly with a
      probability q and she records the performance of her strategies only in the turns
      that she participates. The information, characterized by a quantity called the
      inefficiency, embedded in the agent's strategies performance turns out to be very
      different from that of the other agents. Detailed numerical studies reveal a
      relationship between the success rate of the agent and the inefficiency. The
      relationship can be understood analytically in terms of the dynamics in which the
      various possible histories are being visited as the game proceeds. For a finite
      fraction of randomly participating agents up to 60% of the population, it is
      found that the winning edge of these agents persists.

PMID- 15169083
TI  - Solvable biological evolution model with a parallel mutation-selection scheme.
AB  - Based on the connection between a quantum spin model and an asexual biological
      evolution model with a single-peak fitness function in parallel mutation
      selection scheme, we solve exactly both static and dynamics of the evolution
      model. We find that relaxation in such a parallel scheme is faster than that in a
      connected scheme of Eigen model. Our method can also be extended to other fitness
      functions.

PMID- 15169084
TI  - Formation of an information network in a self-pulsating multimode laser.
AB  - We investigated self-induced pulsations in a globally-coupled microchip multimode
      solid-state laser operating on a Lambda transition. A variety of dynamic states,
      featuring locking of pulsation frequencies, multidimensional quasiperiodic, and
      chaotic pulsations, induced by nonlinear modal interactions were observed
      depending on the number of oscillating modes. The underlying modal interplay was
      characterized in terms of the dynamic statistical quantity of information
      circulations. Mode grouping and information sender-receiver-mediator
      relationships established among mode groups, i.e., "information networks," were
      identified. Observed dynamic states were reproduced by numerical simulation of a
      model equation and each dynamic state was shown to create its own information
      network.

PMID- 15169085
TI  - Chaotic control and synchronization for system identification.
AB  - Research into applications of synchronized chaotic systems assumes that it will
      be necessary to build many different drive-response pairs, but little is known in
      general about designing higher dimensional chaotic flows. In this paper, I do not
      add any design techniques, but I show that it is possible to create multiple
      drive-response pairs from one chaotic system by applying chaos control techniques
      to the drive and response systems. If one can design one chaotic system with the
      desired properties, then many drive-response pairs can be built from this system,
      so that it is not necessary to solve the design problem more than once. I show
      both numerical simulations and experimental work with chaotic circuits. I also
      test the response systems for ability to overcome noise or other interference.

PMID- 15169086
TI  - Thermodynamic formalism for field-driven Lorentz gases.
AB  - We analytically determine the dynamical properties of two-dimensional field
      driven Lorentz gases within the thermodynamic formalism. For dilute gases
      subjected to an isokinetic thermostat, we calculate the topological pressure as a
      function of a temperaturelike parameter beta up to second order in the strength
      of the applied field. The Kolmogorov-Sinai entropy and the topological entropy
      can be extracted from a dynamical entropy defined as a Legendre transform of the
      topological pressure. Our calculations of the Kolmogorov-Sinai entropy exactly
      agree with previous calculations based on a Lorentz-Boltzmann equation approach.
      We give analytic results for the topological entropy and calculate the dimension
      spectrum from the dynamical entropy function.

PMID- 15169087
TI  - Asymmetrical dripping.
AB  - Dripping from a faucet is studied, where by cutting diagonally the tip breaks the
      cylindrical symmetry. We measured long dripping time series recorded with a laser
      beam apparatus and continuous change in drop position using a high-speed camera.
      It is found that the added degree of freedom produces a transversal oscillation
      of a pending drop, which couples with a vertical oscillation induced by the
      breaking off of the previous drop. As a consequence dripping times shorten and
      dripping patterns regularize. The effect is attributed to the "reduced" contact
      circle and to decreased frequency of the vertical oscillations of the residue. A
      very complex flow circulation pattern within the forming drop is observed. It is
      suggested that geometrical shape vibrations of the pending drop take place by the
      development of eddies of different amount, more effective in the vicinity of the
      highest edge of the tip, where they dissipate more slowly. This asymmetrical
      liquid flow is brought about by the slanting form of the orifice and overlaps
      with the axial oscillations.

PMID- 15169088
TI  - Control of Turing pattern formation by delayed feedback.
AB  - The effect of the global delayed feedback technique on Turing pattern formation
      is investigated in the modified Lengyel-Epstein two-variable model. Feedback
      intensity, delay time, and feedback-imposing time (the period of time that
      feedback is present in the system) are all found to be of significant influence
      on Turing pattern formation time. Under appropriate parameter settings, delayed
      feedback could suppress or induce the Turing pattern if the feedback intensity is
      strong enough.

PMID- 15169089
TI  - Synchronized states in a ring of mutually coupled self-sustained electrical
      oscillators.
AB  - We investigate in this paper different states of synchronization in a ring of
      mutually coupled self-sustained electrical oscillators. The good coupling
      parameters leading to complete and partial synchronization or disordered states
      are calculated using the properties of the variational equations of stability. A
      stability map showing domains of synchronization to an external excitation
      locally injected in the ring is also obtained. In both cases, the numerical
      simulation validates and complements the results of the analytical investigation.

PMID- 15169090
TI  - Delay-induced resonances in an optical system with feedback.
AB  - We study the influence of the delay time in the response of a delayed feedback
      system to external periodic driving. The nonlinear system we consider is a
      semiconductor laser with optical feedback operating in the low-frequency
      fluctuation regime. We numerically examine the consequences of varying the
      external cavity length of the system when a weak modulation is introduced through
      the laser's pump current. The harmonic modulation is seen to lead to a partial
      periodic entrainment of power dropouts, and the distribution of time intervals
      between the dropouts exhibits resonances with certain delay times. In other
      words, the response of the system to the external modulation is enhanced for
      particular values of the external cavity length. The same effect can be observed
      in the presence of noise, indicating that stochastic resonance can be enhanced or
      degraded depending on the feedback time.

PMID- 15169091
TI  - Tunable Fano resonances in transport through microwave billiards.
AB  - We present a tunable microwave scattering device that allows the controlled
      variation of Fano line shape parameters in transmission through quantum
      billiards. Transport in this device is nearly fully coherent. By comparison with
      quantum calculations, employing the modular recursive Green's-function method,
      the scattering wave function and the degree of residual decoherence can be
      determined. The parametric variation of Fano line shapes in terms of interacting
      resonances is analyzed.

PMID- 15169092
TI  - Hopf bifurcation cascade in small-alpha laser diodes subject to optical feedback.
AB  - We analyze theoretically the dynamics of a semiconductor laser subject to optical
      feedback, on the basis of the well-known Lang-Kobayashi equations. Previous
      investigations on this laser system suggest that a small linewidth enhancement
      factor (alpha factor) stabilizes the laser dynamics. By contrast, we unveil here
      optical feedback induced instabilities which are present for a small value of
      alpha but which disappear when alpha increases above alpha approximately 1. By
      combining numerical simulations and modern continuation methods for delay
      differential equations, we unveil cascades of subcritical and supercritical Hopf
      bifurcations on the first external-cavity mode (ECM). We unveil for the first
      time, to our knowledge, the occurrence of subcritical Hopf bifurcation points for
      intermediate values of the EC length, i.e. close to the boundary between the
      short and the long EC regimes. They lead to severe laser instabilities such as
      large intensity and possibly chaotic pulsations. Moreover, these Hopf bifurcation
      cascades for small values of alpha are shown to be responsible for different
      bifurcation scenarios leading to restabilization of the first ECM and to ECM
      bistability.

PMID- 15169093
TI  - Influence of a magnetic field on the Soret-effect-dominated thermal convection in
      ferrofluids.
AB  - We investigate theoretically the influence of a magnetic field on the growth of
      convective rolls in a slab of ferrofluid subject to a vertical temperature
      gradient. Due to the pronounced Soret effect of these materials in combination
      with a considerable solutal expansion, a dynamic description as a binary mixture
      is appropriate. We first derive a comprehensive set of magnetic field effects in
      the statics and dynamics of binary mixtures. Among those, the two prominent ones,
      the Kelvin force and magnetophoresis, are studied in detail with respect to their
      influence on the thermal convection behavior. The main difference from the case
      without an external field rests in the importance of the boundary layers, which
      influence the bulk problem through the magnetic boundary conditions. We discuss
      an analytical approximate solution and compare it with a numerical multimode
      expansion.

PMID- 15169094
TI  - Dynamics of a drop at a fluid interface under shear.
AB  - We analyze the dynamics of a two-dimensional drop lying on a fluid interface,
      sometimes called a liquid lens, subjected to simple shear flow. The three fluids,
      the drop and the two external fluids, meet at a triple point (or a triple line in
      three dimensions). A requirement for steady drop shapes is that the triple points
      are stationary. This leads to a flow topology different than that of a freely
      suspended drop. Results are substantiated with numerical results using a level
      set method for interface evolution and treatment of triple points. Possible
      implications for new drop instabilities are also discussed.

PMID- 15169095
TI  - Canonical description of ideal magnetohydrodynamic flows and integrals of motion.
AB  - In the framework of the variational principle the canonical variables describing
      magnetohydrodynamic (MHD) flows of general type (i.e., with spatially varying
      entropy and nonzero values of all topological invariants) are introduced. It is
      shown that the velocity representation of the Clebsch type following from the
      variational principle with constraints is equivalent to that resulting from the
      generalization of the Weber transformation performed in the paper for the case of
      arbitrary MHD flows. Using such complete velocity representation enables us not
      only to describe the general type flows in terms of single-valued functions, but
      also to solve the intriguing problem of the "missing" MHD integrals of motion.
      The set of hitherto known MHD local invariants and integrals of motion appears to
      be incomplete: for the vanishing magnetic field it does not reduce to the set of
      the conventional hydrodynamic invariants. And if the analogs of the vorticity and
      helicity were discussed earlier for the particular cases, the analog of Ertel
      invariant has been so far unknown. It is shown that all "missing" invariants are
      expressed in terms of the decomposition of the velocity representation into the
      "hydrodynamic" and "magnetic" parts. In spite of the nonunique character of such
      representation it is shown that there exists a natural restriction of the gauge
      transformations set allowing one to make the invariants gauge independent. It is
      found that on the basis of the new invariants introduced a wide set of high-order
      invariants can be constructed. The new invariants are relevant both for the
      deeper insight into the problem of the topological structure of the MHD flows as
      a whole and for the examination of the stability problems. The additional
      advantage of the proposed approach is that it enables one to deal with
      discontinuous flows, including all types of possible breaks.

PMID- 15169096
TI  - Decay of magnetohydrodynamic turbulence from power-law initial conditions.
AB  - We derive relations for the decay of the kinetic and magnetic energies and the
      growth of the Taylor and integral scales in unforced, incompressible,
      homogeneous, and isotropic three-dimensional magnetohydrodynamic (3DMHD)
      turbulence with power-law initial energy spectra. We also derive bounds for the
      decay of the cross and magnetic helicities. We then present results from
      systematic numerical studies of such decay both within the context of a MHD shell
      model and direct numerical simulations of 3DMHD. We show explicitly that our
      results about the power-law decay of the energies hold for times t< t*, where t*
      is the time at which the integral scales become comparable to the system size.
      For t< t*, our numerical results are consistent with those predicted by the
      principle of "permanence of large eddies."

PMID- 15169097
TI  - Pattern formation in weakly forced Taylor-Couette flow.
AB  - Low-inertia vortex formation and pattern selection are examined for axisymmetric
      Taylor-Couette flow with spatially modulated cylinders. The forcing is arbitrary
      but remains periodic. The modulation amplitude is assumed to be small, and a
      regular perturbation expansion is used to determine the flow field at small to
      moderately large Taylor numbers (below the critical threshold). It is found that
      the presence of a weak modulation leads unambiguously to the emergence of steady
      Taylor-vortex flow even at vanishingly small Taylor number. This situation is
      closely reminiscent of the effect of end plates, and the consequent onset of
      imperfect bifurcation. The vortex structure is found to have the same periodicity
      as the forcing when only one of the cylinders is modulated, or when the
      modulations are commensurate. For incommensurate modulations, the vortex pattern
      is quasiperiodic, with regions of almost purely azimuthal flow. When the counter
      rotation speed of the outer cylinder increases, the original vortices are
      gradually replaced by new ones that end up spanning the entire gap width, and in
      turn break up into two vortices resulting in two rows of vortices commensurate
      with each cylinder modulation. It is also shown that, for any modulation
      amplitude, the forcing wave number that generates the most intense vortex flow
      for a given Taylor number varies monotonically with Ta, but always reaches the
      critical value predicted by linear stability analysis for straight cylinders,
      regardless of which cylinder is modulated.

PMID- 15169098
TI  - Continuum description of finite-size particles advected by external flows: the
      effect of collisions.
AB  - The equation of the density field of an assembly of macroscopic particles
      advected by a hydro-dynamic flow is derived from the microscopic description of
      the system. This equation allows one to recognize the role and the relative
      importance of the different microscopic processes implicit in the model: the
      driving of the external flow, the inertia of the particles, and the collisions
      among them. The validity of the density description is confirmed by comparisons
      of numerical studies of the continuum equation with direct simulation Monte Carlo
      simulations of hard disks advected by a chaotic flow. We show that the collisions
      have two competing roles: a dispersinglike effect and a clustering effect (even
      for elastic collisions). An unexpected feature is also observed in the system:
      the presence of collisions can reverse the effect of inertia, so that grains with
      lower inertia are more clusterized.

PMID- 15169099
TI  - Long-time evolution of a drop size distribution by coalescence in a linear flow.
AB  - The growth of spherical drops by coalescence in simple shear and axisymmetric
      straining flows has been numerically investigated, and the long-time scaling
      behavior of the system was explored. It is shown that hydrodynamic interactions
      qualitatively modify the the collision kernel in the population balance equation
      and thus alter the evolution of the drop size distribution at long times. In the
      presence of hydrodynamic interactions, the number of drops in the system decays
      as t(-1), and the average drop size grows as e(sqrt[t]); in the absence of
      hydrodynamic interactions, these quantities evolve exponentially at long times.
      Hydrodynamic interactions lead to broader drop size distributions, and cause the
      influence of initial conditions to decay with time. Drops undergoing
      thermocapillary migration are shown to exhibit similar features. Our results are
      shown to be consistent with the established theory for the scaling behavior of
      aggregating systems. It is shown that the theory applies even in certain cases
      where the binary collision kernel does not have the assumed form. In the presence
      of hydrodynamic interactions, the scaling regime is attained slowly
      (logarithmically).

PMID- 15169100
TI  - Negative ion formation and motion in a mixture of CCl4 and Ar.
AB  - This paper deals with the measurement of the mobility of negative ions in the
      mixtures of CCl4 with Ar with the CCl4 ratio up to 33.3%. The pulsed Townsend
      technique was employed to produce an integrated ionic avalanche over a range of
      the density-reduced electric field E/N for which ionization is either negligible
      or absent, and attachment processes are dominant, leading to the formation of
      mostly CCl-4. The E/N range of measurement was 1-50 Td (1 Td=10(-17) V cm(2)).
      Our measurements strongly suggest that attachment is the dominant process and
      only negative ions are formed.

PMID- 15169101
TI  - Ion acceleration by beating electrostatic waves: domain of allowed acceleration.
AB  - The conditions under which a magnetized ion can be accelerated through a
      nonlinear interaction with a pair of beating electrostatic waves are explored. It
      has been shown [Benisti et al., Phys. Plasma 5, 3224 (1998)] that the electric
      field of the beating waves can, under some conditions, accelerate ions from
      arbitrarily low initial velocity in stark contrast with the well-known nonlinear
      threshold criteria for ion acceleration by a single wave. It is shown here that
      the previously found condition is necessary but not sufficient for acceleration
      to occur. The sufficient and necessary conditions are identified in terms of the
      location of the critical points of the motion on the Poincare section. A second
      order perturbation analysis was carried out to approximate the location of these
      critical points and define the domains of allowed and forbidden acceleration. It
      is shown that for an ion to be significantly energized, the Hamiltonian must be
      outside the energy barrier defined by the location of the elliptic and hyperbolic
      critical points. Despite the restriction on the Hamiltonian, an ion with
      arbitrarily low initial velocity may benefit from this acceleration mechanism.

PMID- 15169103
TI  - Energy loss of ions and ion clusters in a disordered electron gas.
AB  - The various aspects of the correlated stopping power of pointlike and extended
      ions moving in a disordered degenerate electron gas have been analytically and
      numerically studied. Within the linear response theory we have made a systematic
      and comprehensive investigation of correlated stopping power, vicinage function,
      and related quantities for protons and extended ions, as well as for their
      clusters. The disorder, which leads to a damping of plasmons and quasiparticles
      in the electron gas, is taken into account through a relaxation time
      approximation in the linear response function. The stopping power for an
      arbitrary extended ion with a single bound electron is calculated in both the low
      and high velocity limits. Our analytical results show that in a high velocity
      limit the main logarithmic contribution to the stopping power for an extended ion
      is significantly modified and for instance, in the case of He+, Li2+, and Be3+
      ions must behave as ln ( A v(5) ), ln ( A v(3.25) ), and ln ( A v(2.77) ),
      respectively where v is the ion velocity. This behavior may be contrasted with
      the usual ln ( v(2) ) dependence for a point ion projectile. It is shown that the
      factor A which depends on the damping can be significantly reduced by increasing
      the latter. In order to highlight the effects of damping we present a comparison
      of our analytical and numerical results, in the case of both pointlike and
      extended ions, obtained for a nonzero damping with those for a vanishing damping.

PMID- 15169102
TI  - X-ray emission from z pinches at 10 7 A: current scaling, gap closure, and shot
      to-shot fluctuations.
AB  - We have measured the x-ray power and energy radiated by a tungsten-wire-array z
      pinch as a function of the peak pinch current and the width of the anode-cathode
      gap at the base of the pinch. The measurements were performed at 13- and 19-MA
      currents and 1-, 2-, 3-, and 4-mm gaps. The wire material, number of wires, wire
      array diameter, wire-array length, wire-array-electrode design, normalized-pinch
      current time history, implosion time, and diagnostic package were held constant
      for the experiments. To keep the implosion time constant, the mass of the array
      was increased as I2 (i.e., the diameter of each wire was increased as I), where I
      is the peak pinch current. At 19 MA, the mass of the 300-wire 20-mm-diam 10-mm
      length array was 5.9 mg. For the configuration studied, we find that to eliminate
      the effects of gap closure on the radiated energy, the width of the gap must be
      increased approximately as I. For shots unaffected by gap closure, we find that
      the peak radiated x-ray power P(r) proportional to I1.24+/-0.18, the total
      radiated x-ray energy E(r) proportional to I1.73+/-0.18, the x-ray-power rise
      time tau(r) proportional to I0.39+/-0.34, and the x-ray-power pulse width tau(w)
      proportional to demonstrate that the internal energy and radiative opacity of the
      pinch are not responsible for the observed subquadratic power scaling. Heuristic
      wire-ablation arguments suggest that quadratic power scaling will be achieved if
      the implosion time tau(i) is scaled as I(-1/3). The measured 1sigma shot-to-shot
      fluctuations in P(r), E(r), tau(r), tau(w), and tau(i) are approximately 12%, 9%,
      26%, 9%, and 2%, respectively, assuming that the fluctuations are independent of
      I. These variations are for one-half of the pinch. If the half observed radiates
      in a manner that is statistically independent of the other half, the variations
      are a factor of 2(1/2) less for the entire pinch. We calculate the effect that
      shot-to-shot fluctuations of a single pinch would have on the shot-success
      probability of the double-pinch inertial-confinement-fusion driver proposed by
      Hammer et al. [Phys. Plasmas 6, 2129 (1999)]. We find that on a given shot, the
      probability that two independent pinches would radiate the same peak power to
      within a factor of 1+/-alpha (where 0< or =alpha<<1) is equal to
      erf(alpha/2sigma), where sigma is the 1sigma fractional variation of the peak
      power radiated by a single pinch. Assuming alpha must be < or =7% to achieve
      adequate odd-Legendre-mode radiation symmetry for thermonuclear-fusion
      experiments, sigma must be <3% for the shot-success probability to be > or =90%.
      The observed (12/2(1/2))%=8.5% fluctuation in P(r) would provide adequate
      symmetry on 44% of the shots. We propose that three-dimensional radiative
      magnetohydrodynamic simulations be performed to quantify the sensitivity of the x
      ray emission to various initial conditions, and to determine whether an imploding
      z pinch is a spatiotemporal chaotic system.

PMID- 15169104
TI  - Blowout regimes of plasma wakefield acceleration.
AB  - A wide region of beam parameters is numerically scanned and the dependence of
      wakefield properties on the beam length and current is clarified for the blowout
      regime of beam-plasma interaction. The main regimes of the plasma response are
      found, which qualitatively differ in the plasma behavior. To characterize the
      efficiency of the energy exchange between the beam and the plasma, the energy
      flux through the comoving window is introduced. Scalings of the energy flux for
      the linear plasma response and the main blowout regimes are studied. The most
      efficient energy transfer occurs in the so-called "strong beam" regime of
      interaction. For this regime, analytical approximations for various aspects of
      the plasma response are obtained.

PMID- 15169105
TI  - Electron acceleration by a self-diverging intense laser pulse.
AB  - Electron acceleration by a laser pulse having a Gaussian radial and temporal
      profile of intensity has been studied. The interaction region is vacuum followed
      by a gas. The starting point of the gas region has been chosen around the point
      at which the peak of the pulse interacts with the electron. The tunnel ionization
      of the gas causes a defocusing of the laser pulse and the electron experiences
      the action of a ponderomotive deceleration at the trailing part of the pulse with
      a lower intensity rather than an acceleration at the rising part of the laser
      pulse with a high intensity, and thus gains net energy. The initial density of
      the neutral gas atoms should be high enough to properly defocus the pulse;
      otherwise the electron experiences some deceleration during the trailing part of
      the pulse and the net energy gain is reduced. The rate of tunnel ionization
      increases with the increase in the laser intensity and the initial density of
      neutral gas atoms, and with the decreases in the laser spot size, which causes
      more defocusing of the laser pulse. The required initial density of neutral gas
      atoms decreases with the increase in the laser intensity and also with the
      decrease in the laser spot size.

PMID- 15169106
TI  - Equation of state for weakly coupled quantum plasmas.
AB  - We calculate thermodynamic properties for a dense hydrogen plasma and a quantum
      electron gas using thermodynamic Green's function techniques. Our perturbation
      approach is appropriate to give reliable results in the weak coupling regime. In
      particular, the contribution of the exchange term of the order e(4) is fully
      included for the nondegenerate case as well as for the dense highly degenerate
      quantum region. We compare our results for the equation of state with data
      obtained by different numerical simulations.

PMID- 15169108
TI  - Numerical investigation of recombination gain in the Li III transition to ground
      state.
AB  - We present a numerical investigation of the parameters characterizing the 2-->1
      transition recombination gain in Li III ions ( 13.5 nm ). The numerical model
      includes the initial optical field ionization of the plasma by an intense 100 fs
      laser pulse, taking into account above threshold ionization heating, particle
      collisions, and spatial effects. Gain is then calculated during the process of
      recombination as the plasma expands and cools. We show that by taking into
      account the non-Maxwellian nature of the electron distribution function in the
      plasma and its spatial distribution, high gain in the 2-->1 transition of Li III
      is feasible under certain initial conditions, even though initial estimates based
      on the energy absorption during the ionization predict very low gain. We
      characterize the behavior of the gain under different pumping parameters and
      initial plasma conditions.

PMID- 15169107
TI  - Emission direction of fast electrons in laser-solid interactions at intensities
      from the nonrelativistic to the relativistic.
AB  - The emission direction of outward-ejecting fast electrons generated in laser
      solid interactions by 30 fs laser pulses is measured for laser intensities
      varying from the nonrelativistic to the relativistic. For an s-polarized incident
      laser beam at nonrelativistic intensities, the ejected electrons are close to the
      polarization direction of the laser beam. With the increase of the laser
      intensity, the ejected electrons are still mainly within the polarization plane,
      but turn away from the laser polarization direction towards the opposite
      direction of the incident laser beam. At relativistic intensities, electrons
      eject towards the direction of the reflected laser beam. The increasing
      ponderomotive force acceleration with the laser intensities might be responsible
      for the observed changes.

PMID- 15169109
TI  - Long-range attraction between particles in dusty plasma and partial surface
      tension of a dusty phase boundary.
AB  - Effective potential of a charged dusty particle moving in homogeneous plasma has
      a negative part that provides attraction between similarly charged dusty
      particles. A depth of this potential well is great enough to ensure both
      stability of crystal structure of dusty plasma and sizable value of surface
      tension of a boundary surface of dusty region. The latter depends on the
      orientation of the surface relative to the ion flow, namely, it is maximal and
      positive for the surface normal to the flow and minimal and negative for the
      surface along the flow. For the most cases of dusty plasma in a gas discharge, a
      value of the first of them is more than sufficient to ensure stability of
      lenticular dusty phase void oriented across the counter-ion flow.

PMID- 15169111
TI  - Angular behavior of synchrotron radiation harmonics.
AB  - The detailed analysis of angular dependence of the synchrotron radiation (SR) is
      presented. Angular distributions of linear and circular polarization integrated
      over all harmonics, well known for relativistic electron energies, are extended
      to include radiation from electrons that are not fully relativistic. In
      particular, we analyze the angular dependence of the integral SR intensity and
      peculiarities of the angular dependence of the first harmonics SR. Studying
      spectral SR intensities, we have discovered their unexpected angular behavior,
      completely different from that of the integral SR intensity; namely, for any
      given synchrotron frequency, maxima of the spectral SR intensities recede from
      the orbit plane with increasing particle energy. Thus, in contrast with the
      integral SR intensity, the spectral ones have the tendency to deconcentrate
      themselves on the orbit plane.

PMID- 15169110
TI  - Simple formulas for the beam lifetime analysis in an electron storage ring.
AB  - Derived are simple and accurate formulas estimating the Touschek and beam-gas
      scattering lifetimes. These formulas are practical rather than theoretical. They
      use only the measured total beam lifetime tau and its time derivative dtau/dt to
      estimate the two lifetimes. The only condition required is suppression or
      saturation of the radiative polarization. As a demonstration, the formulas are
      applied to the Pohang Light Source (PLS) beam lifetime.

PMID- 15169112
TI  - Nonlinear stability of oscillatory wave fronts in chains of coupled oscillators.
AB  - We present a stability theory for kink propagation in chains of coupled
      oscillators and a different algorithm for the numerical study of kink dynamics.
      The numerical solutions are computed using an equivalent integral equation
      instead of a system of differential equations. This avoids uncertainty about the
      impact of artificial boundary conditions and discretization in time. Stability
      results also follow from the integral version. Stable kinks have a monotone
      leading edge and move with a velocity larger than a critical value which depends
      on the damping strength.

PMID- 15169113
TI  - Timing jitter of femtosecond solitons in single-mode optical fibers: a
      perturbation model.
AB  - On the basis of the higher-order nonlinear Schrodinger equation, an extended
      soliton perturbation model is proposed. The evolution equations for the soliton
      parameters and the resultant expressions for timing jitter are derived.
      Subsequently, the model is tested to be correct in the subpicosecond-femtosecond
      regime through direct numerical simulations of the underlying equation by using
      the stochastic split-step Fourier method. It is shown that the results of our
      numerical simulations are in excellent agreement with analytical predictions for
      timing jitter. It is found that the Gordon-Haus jitter for dark solitons is
      nearly 1/sqrt[2] of that for bright solitons, and that the Raman jitter always
      dominates the Gordon-Haus jitter in the femtosecond regime. In particular, the
      stabilities of the solitary waves are demonstrated under the Gaussian white
      noise. It is expected that for bright and dark solitons, the present equations of
      motion would find extensive applications in the high-speed communication systems
      more than those obtained by use of the well-known perturbation theory about the
      nonlinear Schrodinger equation [J. Opt. Soc. Am. B 18, 153 (2001)].

PMID- 15169114
TI  - Theory of photon statistics and optical coherence in a multiple-scattering random
      laser medium.
AB  - We derive the photon-number probability distribution and the resulting degree of
      second-order optical coherence for light emission from a uniformly distributed
      active species within a multiple-light-scattering medium. This is obtained from a
      master equation describing the probability distribution for photons in the
      vicinity of position r, traveling with a wave vector k, related, in turn, to a
      coarse-grained average of the optical Wigner coherence function. Using a simple
      model for isotropic, spatially uncorrelated scatterers, this reduces to a
      generalization of the master equation of a conventional laser in which the medium
      behaves like a random collection of low-quality factor cavities that are coupled
      by photon diffusion between a given cavity and its neighbors. Laserlike
      coherence, on average, is obtained in the random laser above a specific pumping
      threshold. Photon-number statistics above and below the lasing threshold are
      computed by first assuming that the atomic response to the local electromagnetic
      fields is nearly instantaneous. Corrections to this simple model, arising from
      nonadiabatic atomic dynamics, are then estimated. The dependence of the photon
      statistics on scatterer density, gain concentration, and position within a sample
      reveal that, on average, increase of the scattering strength (decrease of the
      photon transport mean free path) in the medium leads to a sharper peak in the
      local photon-number distribution, characteristic of increased local coherence in
      the optical field. We also evaluate the coherence of the output field at points
      outside the random-laser medium. This is a weighted average of radiation emitted
      at different positions in the sample, exhibiting varying degrees of coherence due
      to variations in the local pumping intensity.

PMID- 15169115
TI  - Numerical analysis of the one-mode solutions in the Fermi-Pasta-Ulam system.
AB  - The stability of the one-mode nonlinear solutions of the Fermi-Pasta-Ulam beta
      system is numerically investigated. No external perturbation is considered for
      the one-mode exact analytical solutions, the only perturbation being that
      introduced by computational errors in the numerical integration of motion
      equations. The threshold energy for the excitation of the other normal modes and
      the dynamics of this excitation are studied as a function of the parameter micro
      characterizing the nonlinearity, the energy density epsilon and the number N of
      particles of the system. The results achieved confirm in part previous ones,
      obtained with a linear analysis of the problem of the stability, and clarify the
      dynamics by which a one-mode exchanges energy with the other modes with
      increasing energy density. In a range of energy density near the threshold value
      and for various values of the number of particles N, the nonlinear one-mode
      exchanges energy with the other linear modes for a very short time, immediately
      recovering all its initial energy. This sort of recurrence is very similar to
      Fermi recurrences, even if in the Fermi recurrences the energy of the initially
      excited mode changes continuously and only periodically recovers its initial
      value. A tentative explanation for this intermittent behavior, in terms of
      Floquet's theorem, is proposed. Preliminary results are also presented for the
      Fermi-Pasta-Ulam alpha system which show that there is a stability threshold, for
      large N, independent of N.

PMID- 15169116
TI  - Influence of a defect particle on the structure of a classical two-dimensional
      cluster.
AB  - A system of classical charged particles interacting through a Coulomb repulsive
      potential which are confined in a two-dimensional parabolic trap is studied. We
      allow one or two particles, called defect particles, to have a different mass
      and/or charge than the other particles. The structure of the whole system depends
      on the mass and the charge of the defects and the total number of particles in
      the system. The ground state configurations are investigated and phase diagrams
      are constructed, which explain the recent experimental results of Phys. Rev. E
      64, 11 603 (2001)]]. We found that several of the experimental configurations are
      metastable and that replacing the Coulomb interparticle potential by an inversely
      quadratic one has only a minor effect on the results.

PMID- 15169117
TI  - Emission stimulation in a directional band gap of a CdTe-loaded opal photonic
      crystal.
AB  - An anisotropic photonic crystal light source has been realized by impregnation of
      a thin film latex opal with brightly luminescent CdTe nanocrystals. Its
      photoluminescence along a given direction has been studied as a function of
      excitation power. An increase of the photoluminescence saturation threshold in
      the directional photonic band gap has been observed. This result is interpreted
      as a stimulation of emission coupled to specific eigenmodes of a directional band
      gap. A theoretical model exploiting the low group velocity eigenmodes has been
      elaborated to explain the resonance character of the emission with band gap
      frequencies.

PMID- 15169118
TI  - Efficient control of the energy exchange due to the Manakov vector-soliton
      collision.
AB  - By examining the concept of energy exchange among the orthogonally polarized
      components of each of two colliding (Manakov-like) vector solitons it is observed
      that a maximum or an efficient energy-exchange process is possible only for an
      appropriate choice of the initial physical parameters (namely, frequency
      separation, polarizations, time delay, and pulse-width separation between the
      colliding solitons) for which L(W) (walk-off length) >>L(NL) (nonlinear length).
      However, in this case only, the amount of energy-exchange can be considerably
      increased or decreased by appropriately changing the phases of colliding solitons
      without altering the walk-off length and the initial energy distributions between
      the soliton components. Moreover we observe that during the collision between two
      closely placed vector solitons of the practically interesting integrable Manakov
      model, nonuniform pulse broadening takes place in each of their components. Such
      an effect has not yet been reported in any (1+1) dimensional integrable soliton
      systems so far. In addition, the relation between walk-off length, polarization,
      and pulse width is briefly discussed.

PMID- 15169119
TI  - Tunable filtering and demultiplexing in phononic crystals with hollow cylinders.
AB  - Acoustic band gap (ABG) materials constituted of steel hollow cylinders immersed
      in water can exhibit a tunable narrow pass band (NPB) located inside their gap.
      We theoretically investigate, using the finite difference time domain (FDTD)
      method, the properties of waveguides composed of a row of hollow cylinders in a
      two-dimensional (2D) phononic crystal made of filled steel cylinders. These
      waveguides exhibit NPB's at frequencies slightly higher than their infinite
      periodic ABG counterpart. The frequency of the waveguide's NPB can be selected by
      adjusting the inner radius of the hollow cylinders or by changing the nature of
      the fluid that fills them. We show that a waveguide constituted of a row of
      hollow cylinders with different inner radii can transport waves at two different
      frequencies. By selectively filling the cylinders with water or mercury we have
      created an active device that permits the transmission of waves at one, both, or
      neither of these frequencies. Finally, we examine the multiplexing and
      demultiplexing capabilities of Y shaped waveguides constituted of hollow
      cylinders.

PMID- 15169120
TI  - Mode matching interface for efficient coupling of light into planar photonic
      crystals.
AB  - In order to integrate superdispersive elements based on photonic crystals, such
      as the superprism, with conventional integrated optics, insertion losses at the
      interface to the photonic crystal need to be reduced to an acceptable level. We
      describe a mode matching interface composed of cascaded diffraction gratings that
      generates the field profile of the photonic crystal Bloch mode from a slab mode.
      We calculate with three-dimensional finite-difference time-domain computation
      that by interposing such a multilayered grating between an unpatterned slab and a
      planar photonic crystal, the insertion efficiency is enhanced from 9% to 84%.
      Each diffraction grating consists of a row of holes and does not require any
      additional process steps from those used to fabricate the planar photonic
      crystal. In order to optimize the efficiency of the mode matching interface,
      constructive interference conditions are imposed between successive gratings and
      reflections from individual gratings are suppressed. We fabricate devices in
      silicon on insulator material and show experimental evidence of the Bloch mode
      structure and of the mode matching mechanism.

PMID- 15169121
TI  - Extracting the Green's function from the correlation of coda waves: a derivation
      based on stationary phase.
AB  - The Green's function of waves that propagate between two receivers can be found
      by cross-correlating multiply scattered waves recorded at these receivers. This
      technique obviates the need for a source at one of these locations, and is
      therefore called "passive imaging." This principle has been explained by assuming
      that the normal modes of the system are uncorrelated and that all carry the same
      amount of energy (equipartitioning). Here I present an alternative derivation of
      passive imaging of the ballistic wave that is not based on normal modes. The
      derivation is valid for scalar waves in three dimensions, and for elastic surface
      waves. Passive imaging of the ballistic wave is based on the destructive
      interference of waves radiated from scatterers away from the receiver line, and
      the constructive interference of waves radiated from secondary sources near the
      receiver line. The derivation presented here shows that the global requirement of
      the equipartitioning of normal modes can be relaxed to the local requirement that
      the scattered waves propagate on average isotropically near the receivers.

PMID- 15169122
TI  - Forward scattering of light in thin opal films.
AB  - Angle-resolved spectra of the light scattered in a thin opal film have been
      measured behind the sample in three configurations, which differ by directions of
      the light incidence and detection. Two minima have been observed in scattering
      spectra and assigned to the attenuation by the (111) Bragg photonic bandgap along
      directions of the incident and detected photon flux. The irrelevance of the
      photonic bandgap minima to the actual path of scattered photon has been
      demonstrated. The projection of the directional (111) photonic band gap has been
      allotted to the plateau observed in the angle diagrams of the scattered light
      intensity. The spectra and the angle diagrams of the scattered light have been
      interpreted in terms of the weak scattering regime, when scattering serves for
      coupling a photon from one eigenmode of opal to another.

PMID- 15169123
TI  - Radiation-induced interaction of optical solitons in fibers with randomly varying
      birefringence.
AB  - We study propagation of solitons in optical fibers with randomly varying
      birefringence which results in polarization mode dispersion. Due to the disorder,
      solitons emit radiation, i.e., the energy of the solitons is partly transferred
      into the delocalized modes. The radiation serves as a mediator of the
      intersoliton interaction leading to fluctuations of the soliton separations. We
      establish statistics of the fluctuations which is found to be sensitive to the
      phase mismatches and mutual polarizations of the solitons, and independent of the
      soliton separation. The theoretical results are justified by direct numerical
      simulations.

PMID- 15169124
TI  - Seminumerical method for tracking multibreathers in Klein-Gordon chains.
AB  - We present a method of numerical calculation of multibreathers in Klein-Gordon
      chains. This method provides in advance the linear stability of the calculated
      multibreather solutions. We illustrate the method by calculating initial
      conditions for multibreathers in a chain of coupled Morse oscillators.

PMID- 15169125
TI  - Underlying mechanism of numerical instability in large-eddy simulation of
      turbulent flows.
AB  - This paper extends our recent theoretical work concerning the feasibility of
      stable and accurate computation of turbulence using a large eddy simulation
      [Phys. Rev. E 68, 036705 (2003)]]. In our previous paper, it was shown, based on
      a simple assumption regarding the instantaneous streamwise velocity, that the
      application of the Gaussian filter to the incompressible Navier-Stokes equations
      can result in the appearance of a numerically unstable term that can be
      decomposed into positive and negative viscosities. That result raises the
      question as to whether an accurate solution can be achieved by a numerically
      stable subgrid-scale model. In the present paper, based on assumptions regarding
      the statistically averaged velocity, we present similar theoretical
      investigations to show that in several situations, the shears appearing in the
      statistically averaged velocity field numerically destabilize the fluctuation
      components because of the derivation of a numerically unstable term that
      represents negative diffusion in a fixed direction. This finding can explain the
      problematic numerical instability that has been encountered in large eddy
      simulations of wall-bounded flows. The present result suggests that this
      numerical problem is universal in large eddy simulations, and that if there is no
      failure in modeling, the resulting subgrid-scale model can still have unstable
      characteristics; that is, the known instability problems of several existing
      subgrid-scale models are not something that one may remove simply by an
      artificial technique, but must be taken seriously so as to treat them accurately.

PMID- 15169126
TI  - Computing induced charges in inhomogeneous dielectric media: application in a
      Monte Carlo simulation of complex ionic systems.
AB  - The efficient calculation of induced charges in an inhomogeneous dielectric is
      important in simulations and coarse-grained models in molecular biology, chemical
      physics, and electrochemistry. We present the induced charge computation (ICC)
      method for the calculation of the polarization charges based on the variational
      formulation of Allen et al. [Phys. Chem. Chem. Phys. 3, 4177 (2001)]. We give a
      different solution for their extremum condition that produces a matrix
      formulation. The induced charges are directly calculated by solving the linear
      matrix equation Ah=c, where h contains the discretized induced charge density, c
      depends only on the source charges-the ions moved in the simulation-and the
      matrix A depends on the geometry of dielectrics, which is assumed to be unchanged
      during the simulation. Thus, the matrix need be inverted only once at the
      beginning of the simulation. We verify the efficiency and accuracy of the method
      by means of Monte Carlo simulations for two special cases. In the simplest case,
      a single sharp planar dielectric boundary is present, which allows comparison
      with exact results calculated using the method of electrostatic images. The other
      special case is a particularly simple case where the matrix A is not diagonal: a
      slab with two parallel flat boundaries. Our results for electrolyte solutions in
      these special cases show that the ICC method is both accurate and efficient.

PMID- 15169127
TI  - Explanation of power law behavior of autoregressive conditional duration
      processes based on the random multiplicative process.
AB  - Autoregressive conditional duration (ACD) processes, which have the potential to
      be applied to power law distributions of complex systems found in natural
      science, life science, and social science, are analyzed both numerically and
      theoretically. An ACD(1) process exhibits the singular second order moment, which
      suggests that its probability density function (PDF) has a power law tail. It is
      verified that the PDF of the ACD(1) has a power law tail with an arbitrary
      exponent depending on a model parameter. On the basis of theory of the random
      multiplicative process a relation between the model parameter and the power law
      exponent is theoretically derived. It is confirmed that the relation is valid
      from numerical simulations. An application of the ACD(1) to intervals between two
      successive transactions in a foreign currency market is shown.

PMID- 15169129
TI  - Convective instabilities of synchronization manifolds in spatially extended
      systems.
AB  - We study the stability properties of anticipating synchronization in an open
      chain of unidirectionally coupled identical chaotic oscillators. Despite being
      absolutely stable, the synchronization manifold is unstable to propagating
      perturbations. We analyze and characterize such instabilities drawing a
      qualitative and quantitative comparison with the convective instabilities typical
      of spatially extended systems.

PMID- 15169128
TI  - Modulated amplitude waves in Bose-Einstein condensates.
AB  - We analyze spatiotemporal structures in the Gross-Pitaevskii equation to study
      the dynamics of quasi-one-dimensional Bose-Einstein condensates (BECs) with mean
      field interactions. A coherent structure ansatz yields a parametrically forced
      nonlinear oscillator, to which we apply Lindstedt's method and multiple-scale
      perturbation theory to determine the dependence of the intensity of periodic
      orbits ("modulated amplitude waves") on their wave number. We explore BEC band
      structure in detail using Hamiltonian perturbation theory and supporting
      numerical simulations.

PMID- 15169130
TI  - Scalar gradient fields by geometric measure theory.
AB  - Upper bounds of the Hausdorff volume of scalar gradient field graphs are derived
      by means of geometric measure theory. The approach reproduces that scalar
      gradient fields along a mean imposed scalar gradient become space filling for
      sufficiently high values of Schmidt numbers Sc. The bounds are consistent with
      findings from recent high-resolution numerical experiments for 1< or =Sc< or =64,
      but too rough when compared with numerical simulations. A Reynolds number
      dependence of the bounds is found due to the additional scalar gradient
      stretching term in the equation of motion.

PMID- 15169131
TI  - Generation of zonal magnetic fields by low-frequency dispersive electromagnetic
      waves in a nonuniform dusty magnetoplasma.
AB  - It is shown that zonal magnetic fields can be parametrically excited by low
      frequency dispersive driftlike compressional electromagnetic (DDCEM) modes in a
      nonuniform dusty magnetoplasma. For this purpose, we derive a pair of coupled
      equations which exhibits the nonlinear coupling between DDCEM modes and zonal
      magnetic fields. The coupled mode equations are Fourier analyzed to derive a
      nonlinear dispersion relation. The latter depicts that zonal magnetic fields are
      nonlinearly generated at the expense of the low-frequency DDCEM wave energy. The
      relevance of our investigation to the transfer of energy from short scale DDCEM
      waves to long scale zonal magnetic field structures in dark molecular clouds is
      discussed.

PMID- 15169132
TI  - Anomalies of weakened decoherence criteria for quantum histories.
AB  - The theory of decoherent histories is checked for the requirement of statistical
      independence of subsystems. Strikingly, this is satisfied only when the
      decoherence functional is diagonal in both its real and imaginary parts. Although
      the weakened condition of consistency (or weak decoherence), allowing a
      nondiagonal imaginary part, is sufficient for the assignment of probabilities, it
      may easily violate the statistical independence of subsystems. Therefore,
      weakened consistency conditions and various related generalizations of the
      concept of decoherent histories appear to be ruled out. The same conclusion is
      obtained independently, by claiming a plausible dynamical robustness of
      decoherent histories.

PMID- 15169133
TI  - Excitation spectroscopy of vortex lattices in a rotating Bose-Einstein
      condensate.
AB  - Excitation spectroscopy of vortex lattices in rotating Bose-Einstein condensates
      is described. We numerically obtain the Bogoliubov-de Gennes quasiparticle
      excitations for a broad range of energies and analyze them in the context of the
      complex dynamics of the system. Our work is carried out in a regime in which
      standard hydrodynamic assumptions do not hold, and includes features not readily
      contained within existing treatments.

PMID- 15169134
TI  - Ultracold fermions and the SU(N) Hubbard model.
AB  - We investigate the fermionic SU(N) Hubbard model on the two-dimensional square
      lattice for weak to moderate interactions using renormalization group and mean
      field methods. For the repulsive case U>0 at half filling and small N the
      dominant tendency is towards breaking of the SU(N) symmetry. For N>6 staggered
      flux order takes over as the dominant instability, in agreement with the large-N
      limit. Away from half filling for N=3 two flavors remain half filled by
      cannibalizing the third flavor. For U<0 and odd N a full Fermi surface coexists
      with a superconductor. These results may be relevant to future experiments with
      cold fermionic atoms in optical lattices.

PMID- 15169135
TI  - Reconstructing the density of states by history-dependent metadynamics.
AB  - We present a novel method for the calculation of the energy density of states
      D(E) for systems described by classical statistical mechanics. The method builds
      on an extension of a recently proposed strategy that allows the free-energy
      profile of a canonical system to be recovered within a preassigned accuracy
      [Proc. Natl. Acad. Sci. U.S.A. 99, 12562 (2002)]]. The method allows a good
      control over the error on the recovered system entropy. This fact is exploited to
      obtain D(E) more efficiently by combining measurements at different temperatures.
      The accuracy and efficiency of the method are tested for the two-dimensional
      Ising model (up to size 50 x 50) by comparison with both exact results and
      previous studies. This method is a general one and should be applicable to more
      realistic model systems.

PMID- 15169136
TI  - New nucleosynthesis constraint on the variation of G.
AB  - Big bang nucleosynthesis can provide, via constraints on the expansion rate at
      that time, limits on possible variations in Newton's constant, G. The original
      analyses were performed before an independent measurement of the baryon-to-photon
      ratio from the cosmic microwave background was available. Combining this with
      recent measurements of the primordial deuterium abundance in quasar absorption
      systems now allows one to derive a new tighter constraint on G without recourse
      to considerations of helium or lithium abundances. We find that, compared to
      today's value, G0, G(BBN)/G(0)=1.01(+0.20)(-0.16) at the 68% confidence level.

PMID- 15169137
TI  - Charged-particle decay and suppression of primordial power on small scales.
AB  - We study the suppression of the small-scale power spectrum due to the decay of
      charged matter to dark matter prior to recombination. Prior to decay, the charged
      particles couple to the photon-baryon fluid and participate in its acoustic
      oscillations. However, after these charged particles decay to neutral dark
      matter, the photon-baryon fluid is coupled only gravitationally to the newly
      created dark matter. This generically leads to suppression of power on length
      scales that enter the horizon prior to decay. For decay times of approximately
      3.5 yr this leads to suppression of power on subgalactic scales, bringing the
      observed number of galactic substructures in line with observation. Decay times
      of a few years are possible if the dark matter is purely gravitationally
      interacting, such as the gravitino in supersymmetric models or a massive Kaluza
      Klein graviton in models with universal extra dimensions.

PMID- 15169140
TI  - Evidence for M1 scissors resonances built on the levels in the quasicontinuum of
      163Dy.
AB  - Spectra of two-step gamma cascades following the thermal 162Dy(n,gamma)163Dy
      reaction have been measured. Distinct peaklike structures observed at the
      midpoints of these spectra are interpreted as a manifestation of the low-energy
      isovector M1 vibrational mode of excited 163Dy nuclei.

PMID- 15169142
TI  - Influence of molecular structure on double ionization of N2 and O2 by high
      intensity ultrashort laser pulses.
AB  - The electron momentum correlation after nonsequential double ionization of N2 and
      O2 in ultrashort light pulses at light intensities near 1.5 x 10(14) W/cm(2) has
      been investigated. The experimental results reveal distinctive differences
      between the molecular species and between molecules and atoms of similar
      ionization threshold. We provide evidence that recollision double ionization is
      the essential mechanism and trace the origin of the differences back to the
      symmetry of the orbitals occupied by the valence electrons.

PMID- 15169141
TI  - New approach for measuring properties of rp-process nuclei.
AB  - A new experimental approach was developed that can reduce the uncertainties in
      astrophysical rapid proton capture (rp) process calculations due to nuclear data.
      This approach utilizes neutron removal from a radioactive ion beam to populate
      the nuclear states of interest. Excited states were deduced by the gamma-decay
      spectra measured in a semiconductor Ge-detector array. In the first case studied,
      33Ar, excited states were measured with uncertainties of several keV. The 2
      orders of magnitude improvement in the uncertainty of the level energies resulted
      in a 3 orders of magnitude improvement in the uncertainty of the calculated
      32Cl(p,gamma)33Ar rate that is critical to the modeling of the rp process. This
      approach has the potential to measure key properties of almost all interesting
      nuclei on the rp-process path.

PMID- 15169143
TI  - Slowing heavy, ground-state molecules using an alternating gradient decelerator.
AB  - We have decelerated a supersonic beam of 174YbF molecules using a switched
      sequence of electrostatic field gradients. These molecules are 7 times heavier
      than any previously decelerated. An alternating gradient structure allows us to
      decelerate and focus the molecules in their ground state. We show that the
      decelerator exhibits the axial and transverse stability required to bring the
      molecules to rest. Our work significantly extends the range of molecules amenable
      to this powerful method of cooling and trapping.

PMID- 15169145
TI  - Observation of enhanced field-free molecular alignment by two laser pulses.
AB  - We show experimentally that field-free alignment of iodobenzene molecules,
      induced by a single, intense, linearly polarized 1.4-ps-long laser pulse, can be
      strongly enhanced by dividing the pulse into two optimally synchronized pulses of
      the same duration. For a given total energy of the two-pulse sequence the degree
      of alignment is maximized with an intensity ratio of 1:3 and by sending the
      second pulse near the time where the alignment created by the first pulse peaks.

PMID- 15169144
TI  - Two-dimensional Bose-Einstein condensate in an optical surface trap.
AB  - We report on the creation of a two-dimensional Bose-Einstein condensate of cesium
      atoms in a gravito-optical surface trap. The condensate is produced a few microm
      above a dielectric surface on an evanescent-wave atom mirror. After evaporative
      cooling by all-optical means, expansion measurements for the tightly confined
      vertical motion show energies well below the vibrational energy quantum. The
      presence of a condensate is observed in two independent ways by a magnetically
      induced collapse at negative scattering length and by measurements of the
      horizontal expansion.

PMID- 15169146
TI  - Coupling of electron orbital motion with rotation in the high Rydberg states of
      BH.
AB  - We have applied optical-optical-optical triple resonance spectroscopy to resolve
      a system of high Rydberg states in BH that serves quantitatively to characterize
      a fundamental example of electron-orbital-cation core rotational coupling. The
      third-color ionization-detected absorption spectrum originating from the
      photoselected 3s B1Sigma+ Rydberg state with vibrational and total angular
      momentum quantum numbers, v'=1 and N'=0 consists entirely of vibrationally
      autoionizing resonances for which final N=1 that converge in series to the
      BH+v+=1 rotational limits, N+=0, 1, and 2. For series with l=1 converging to N+=0
      and 2, Rydberg orbital and rotational angular momenta couple to systematically
      perturb level energies and distribute lifetime in a well-isolated two-channel
      rotronic interaction that spans hundreds of wave numbers.

PMID- 15169147
TI  - Evaporative cooling of helium nanodroplets with angular momentum conservation.
AB  - Evaporative cooling of helium nanodroplets is studied with a statistical rate
      model that includes, for the first time, angular momentum conservation. While the
      final temperature of the droplets is almost identical to that previously
      predicted and later observed, the distribution of total droplet energy and
      angular momentum states is vastly more excited than a canonical distribution at
      the same temperature. It is found that the final angular momentum of the droplets
      is highly correlated with the initial direction, and that a significant fraction
      of the alignment of the total angular momentum should be transferred to the
      rotational angular momentum of an embedded molecule.

PMID- 15169148
TI  - Crossed beam pump and probe dynamics in metal clusters.
AB  - We investigate theoretically pump and probe dynamics in metal clusters with
      crossed-polarization laser beams. We explore the relation between the pronounced
      Mie plasmon resonance and the laser frequency. The resonance moves with the
      cluster radius and splits according to the actual deformation. We demonstrate
      that probe pulses with different (linear) polarization axes allow one to resolve
      the global shape oscillations of the cluster in monopole and quadrupole degrees
      of freedom.

PMID- 15169139
TI  - Upper bound on the decay tau-->microgamma from the Belle detector.
AB  - We have performed a search for the lepton-flavor-violating decay tau-->microgamma
      using a data sample of 86.3 fb(-1) accumulated by the Belle detector at KEK. No
      evidence for a signal is seen, and we set an upper limit for the branching
      fraction of B(tau-->microgamma)<3.1 x 10(-7) at the 90% confidence level.

PMID- 15169150
TI  - Mesoscopic correlation with polarization rotation of electromagnetic waves.
AB  - Mesoscopic correlations are observed in the polarization of microwave radiation
      transmitted through a random waveguide. These measurements, supported by
      diagrammatic theory, permit an unambiguous decomposition of the intensity
      correlation function of a vector wave into short, long, and infinite range
      components. Infinite range correlation that leads to universal conductance
      fluctuations is measured and found to be in agreement with calculations. The long
      and infinite range components include nonuniversal frequency-independent terms
      associated with coupling into and out of the sample.

PMID- 15169151
TI  - Impact of weak localization in the time domain.
AB  - We find a renormalized "time-dependent diffusion coefficient," D(t), for pulsed
      excitation of a nominally diffusive sample by solving the Bethe-Salpeter equation
      with recurrent scattering. We observe a crossover in dynamics in the
      transformation from a quasi-1D to a slab geometry implemented by varying the
      ratio of the radius, R, to the length, L, of the cylindrical sample with
      reflecting side walls and open ends. Immediately after the peak of the
      transmitted pulse, D(t) falls linearly with a nonuniversal slope that approaches
      an asymptotic value for R/L>>1. The value of D(t) extrapolated to t=0 depends
      only upon the dimensionless conductance g for R/L<<1 and only upon kl(0) for
      R/L>>1, where k is the wave vector and l(0) is the bare mean free path.

PMID- 15169152
TI  - Reactive particles in random flows.
AB  - We study the dynamics of chemically or biologically active particles advected by
      open flows of chaotic time dependence, which can be modeled by a random time
      dependence of the parameters on a stroboscopic map. We develop a general theory
      for reactions in such random flows, and derive the reaction equation for this
      case. We show that there is a singular enhancement of the reaction in random
      flows, and this enhancement is increased as compared to the nonrandom case. We
      verify our theory in a model flow generated by four point vortices moving
      chaotically.

PMID- 15169149
TI  - Excited-state relaxation of Ag8 clusters embedded in helium droplets.
AB  - Neutral silver clusters Ag(N) are grown in ultracold helium nanodroplets. By
      exploiting a strong absorption resonance recently found for Ag8, first
      photoelectron spectra of this neutral species are recorded. Variation of the
      laser photon energy reveals that direct vertical two-photon ionization is
      hindered by rapid relaxation into the lower edge of a long-living excited state
      manifold. The analysis of the dynamics gives a precise value of (6.89+/-0.09) eV
      for the vertical ionization potential of Ag8. The influence of the helium matrix
      on photoemission is discussed.

PMID- 15169153
TI  - Diffusion and mixing in gravity-driven dense granular flows.
AB  - We study the transport properties of particles draining from a silo using imaging
      and direct particle tracking. The particle displacements show a universal
      transition from superdiffusion to normal diffusion, as a function of the distance
      fallen, independent of the flow speed. In the superdiffusive (but sub-ballistic)
      regime, which occurs before a particle falls through its diameter, the
      displacements have fat-tailed and anisotropic distributions. In the diffusive
      regime, we observe very slow cage breaking and Peclet numbers of order 100,
      contrary to the only previous microscopic model (based on diffusing voids).
      Overall, our experiments show that diffusion and mixing are dominated by
      geometry, consistent with long-lasting contacts but not thermal collisions, as in
      normal fluids.

PMID- 15169154
TI  - Noise, coherent fluctuations, and the onset of order in an oscillated granular
      fluid.
AB  - We study fluctuations in a vertically oscillated layer of grains below the
      critical acceleration for the onset of ordered standing waves. As onset is
      approached, transient disordered waves with a characteristic length scale emerge
      and increase in power and coherence. The scaling behavior and the shift in the
      onset of order agrees with the Swift-Hohenberg theory for convection in fluids.
      However, the noise in the granular system is an order of magnitude larger than
      the thermal noise in the most sensitive convecting fluid experiments to date; the
      effect of the granular noise is observable 20% below the onset of order.

PMID- 15169138
TI  - Cross sections and transverse single-spin asymmetries in forward neutral-pion
      production from proton collisions at sqrt[s]=200 GeV.
AB  - Measurements of the production of forward high-energy pi(0) mesons from
      transversely polarized proton collisions at sqrt[s]=200 GeV are reported. The
      cross section is generally consistent with next-to-leading order perturbative QCD
      calculations. The analyzing power is small at x(F) below about 0.3, and becomes
      positive and large at higher x(F), similar to the trend in data at sqrt[s]< or
      =20 GeV. The analyzing power is in qualitative agreement with perturbative QCD
      model expectations. This is the first significant spin result seen for particles
      produced with p(T)>1 GeV/c at a polarized proton collider.

PMID- 15169155
TI  - Cavitation inception on microparticles: a self-propelled particle accelerator.
AB  - Corrugated, hydrophilic particles with diameters between 30 and 150 microm are
      found to cause cavitation inception at their surfaces when they are exposed to a
      short, intensive tensile stress wave. The growing cavity accelerates the particle
      into translatory motion until the tensile stress decreases, and subsequently the
      particle separates from the cavity. The cavity growth and particle detachment are
      modeled by considering the momentum of the particle and the displaced liquid. The
      analysis suggests that all particles which cause cavitation are accelerated into
      translatory motion, and separate from the cavities they themselves nucleate.
      Thus, in the research of cavitation nuclei the link is established between
      developed cavitation bubbles and their origin.

PMID- 15169156
TI  - Ordering phenomena in cooling granular mixtures.
AB  - We report two phenomena, induced by dynamical correlations, that occur during the
      free cooling of a two-dimensional mixture of inelastic hard disks. First, we show
      that, due to the onset of velocity correlations, the ratio of the kinetic
      energies associated with the two species changes from the value corresponding to
      the homogeneous cooling state to a value approximately given by the mass ratio
      m(1)/m(2) of the two species. Second, we report a novel segregation effect that
      occurs in the late stage of cooling, where interconnected domains appear.
      Spectral analysis of the composition field reveals the emergence of a growing
      characteristic length.

PMID- 15169157
TI  - Space-charge driven emittance growth in a 3D mismatched anisotropic beam.
AB  - We investigate the phenomenon of space-charge driven emittance growth in a three
      dimensional mismatched anisotropic charged particle beam with relevance to high
      intensity linear accelerators. The final emittance growth can be understood as a
      superposition of the contributions from the mismatch-induced halo formation and
      from the anisotropy-induced energy exchange. The averaged emittance growth per
      degree of freedom is bounded from above by the so-called "free energy limit"
      extended by the contributions from energy exchange. The partition of the growth
      into longitudinal or transverse is, however, a strong function of the tune ratio
      including the possibility that an initially equipartitioned beam is even driven
      substantially away from equipartition. The growth of the beam halo extent is
      dominated by the effect of mismatch, whereas anisotropy itself generates
      practically no halo.

PMID- 15169159
TI  - Modeling of a lower-hybrid current drive by including spectral broadening induced
      by parametric instability in tokamak plasmas.
AB  - By incorporating parametric instabilities of lower hybrid (LH) waves into a ray
      tracing Fokker-Planck code, accurate simulations of the LH deposition profiles
      are provided, which are useful for interpreting the long-lasting internal
      transport barriers (ITBs) sustained by lower hybrid current drive (LHCD) on JET
      (Joint European Torus). Utilizing the new model, the simulation of the q-profile
      evolution results in agreement with that provided by the motional Stark effect
      reconstructed equilibria. Low magnetic shear (s approximately equal to 0) is
      produced by LHCD in a layer close to the ITB radial foot.

PMID- 15169158
TI  - Strong reduction of the degree of spatial coherence of a laser beam propagating
      through a preformed plasma.
AB  - A strong reduction of the spatial coherence of a laser beam after its propagation
      through a plasma has been measured using a Fresnel biprism interferometer. The
      laser beam was diffraction limited; the coherence width was reduced from 40 mm in
      vacuum down to a few mm with the plasma. Numerical results based on a paraxial
      model exhibit a coherence degree close to the experimental one; they also prove
      the importance of taking into account the nonlocal transport effects in numerical
      simulations for such plasma conditions.

PMID- 15169160
TI  - Highly efficient relativistic-ion generation in the laser-piston regime.
AB  - An intense laser-plasma interaction regime of the generation of high density
      ultrashort relativistic ion beams is suggested. When the radiation pressure is
      dominant, the laser energy is transformed efficiently into the energy of fast
      ions.

PMID- 15169161
TI  - Highly resolved fluid flows: "liquid plasmas" at the kinetic level.
AB  - Fluid flow around an obstacle was observed at the kinetic (individual particle)
      level using "complex (dusty) plasmas" in their liquid state. These "liquid
      plasmas" have bulk properties similar to water (e.g., viscosity), and a
      comparison in terms of similarity parameters suggests that they can provide a
      unique tool to model classical fluids. This allows us to study "nanofluidics" at
      the most elementary-the particle-level, including the transition from fluid
      behavior to purely kinetic transport. In this (first) experimental investigation
      we describe the kinetic flow topology, discuss our observations in terms of fluid
      theories, and follow this up with numerical simulations.

PMID- 15169163
TI  - Theory for explosive ideal magnetohydrodynamic instabilities in plasmas.
AB  - Flux tubes confined in tokamaks are observed to erupt explosively in some plasma
      disruptions and edge localized modes. Similar eruptions occur in astrophysical
      plasmas, for example, in solar flares and magnetospheric substorms. A single
      unifying nonlinear evolution equation describing such behavior in both
      astrophysical and tokamak plasmas is derived. This theory predicts that flux
      tubes rise explosively, narrow, and twist to pass through overlying magnetic
      field lines without reconnection.

PMID- 15169162
TI  - Bifurcation and Lorentz-factor scaling of relativistic magnetized plasma
      expansion.
AB  - We report the long-term results of 2 1/2-dimensional particle-in-cell simulations
      of the relativistic expansion of strongly magnetized electron-positron plasmas.
      When the simulation is carried to >150 light-crossing time of the initial plasma,
      the plasma pulse exhibits a number of remarkable properties. These include the
      repeated bifurcation of the pulse profile, development of a power-law momentum
      distribution with low-energy cutoff, and a simple scaling law for the peak
      Lorentz factor.

PMID- 15169164
TI  - Amplification of ultrashort laser pulses by a resonant Raman scheme in a gas-jet
      plasma.
AB  - Raman amplification of subpicosecond laser pulses up to 95 times is demonstrated
      at corresponding frequencies in a gas-jet plasma. The larger amplification is
      accompanied by a broader bandwidth and shorter pulse duration. Theoretical
      simulations show a qualitative agreement with the measurements, and the effects
      of the plasma conditions and laser intensities are discussed.

PMID- 15169165
TI  - Excitations of the orbital order in RMnO3 manganites: light scattering
      experiments.
AB  - Raman spectroscopy was used to seek out the orbital excitations in orbitally
      ordered RMnO3. The high energy Raman peaks are found to correspond to second and
      third order phonons which couple in some degree to the orbital order. Franck
      Condon-type Raman resonance of multiphonons is observed but the cross sections
      are smaller than expected. A surging emission band at 1.5 eV, detected at high
      temperatures, disappears when the orbital order is established. The crossing of
      the configurational coordinate diagrams of the localized 3d Mn lowest levels, in
      the orbitally ordered state, originates the nonradiative relaxation and the
      quenching of the luminescence.

PMID- 15169166
TI  - Mechanical properties of nanosprings.
AB  - Nanostructures (nanotubes, nanowires, etc.) have been the object of intense
      theoretical and experimental investigations in recent years. Among these
      structures, helical nanosprings or nanocoils have attracted particular interest
      due to their special mechanical properties. In this work, we investigated
      structural properties of nanosprings in the Kirchhoff rod model. We derived
      expressions that can be used experimentally to obtain nanospring Young's modulus
      and Poisson's ratio values. Our results also might explain why the presence of
      catalytic particles is so important in nanostructure growth.

PMID- 15169167
TI  - Stability and mobility of mono- and di-interstitials in alpha-Fe.
AB  - We report a detailed ab initio study of the stability and migration of self
      interstitial atoms (SIAs) and di-interstitials (di-SIAs) in alpha-Fe. The <110>
      dumbbell is confirmed to be the most stable SIA configuration, 0.7 eV below the
      <111> dumbbell. The lowest-energy migration path corresponds to a nearest
      neighbor translation-rotation jump with a barrier of 0.34 eV. The most stable
      configuration for di-SIAs consists of <110> parallel dumbbells. Their migration
      mechanism is similar to that for SIAs, with an activation energy of 0.42 eV.
      These results are at variance with predictions from existing empirical potentials
      and allow one to reconcile theory with experiments.

PMID- 15169168
TI  - Driving force of stacking-fault formation in SiC p-i-n diodes.
AB  - The driving force of stacking-fault expansion in SiC p-i-n diodes was
      investigated using optical emission microscopy and transmission electron
      microscopy. The stacking-fault expansion and properties of the partial
      dislocations were inconsistent with any stress as the driving force. A
      thermodynamic free energy difference between the perfect and a faulted structure
      is suggested as a plausible driving force in the tested diodes, indicating that
      hexagonal polytypes of silicon carbide are metastable at room temperature.

PMID- 15169169
TI  - Metal-to-semimetal transition in supercooled liquid silicon.
AB  - Computer simulations, using the Stillinger-Weber potential, have previously been
      employed to demonstrate a liquid-liquid transition in supercooled silicon near
      1060 K. From calculations of electronic structure using an empirical
      psuedopotential, we show that silicon undergoes an associated metal to semimetal
      transition with a resistivity jump of roughly 1 order of magnitude. We show that
      the electronic states near the Fermi energy become localized in the low
      temperature phase, and that changes in electronic structure between the two
      phases arise from a change in atomic structure, and not from a change in density.

PMID- 15169170
TI  - Bridging the gap between macro- and nanotribology: a quartz crystal microbalance
      study of tricresylphosphate uptake on metal and oxide surfaces.
AB  - We report a quartz crystal microbalance study of the nanodynamical properties of
      tricresylphosphate (TCP) reaction films formed on high purity Fe, Cr, Fe oxide,
      and Cr oxide surfaces at elevated temperatures. The data reveal trace levels of
      interfacial slippage, potentially in conjunction with viscoelastic effects, for
      reaction films characterized by very low macroscopic friction coefficients. In
      contrast, rigidly attached TCP reaction films are observed in systems
      characterized by high macroscopic friction coefficients.

PMID- 15169171
TI  - Nanotube wires on commensurate InAs surfaces: binding energies, band alignments,
      and bipolar doping by the surfaces.
AB  - Using first-principles methods, we study the physicochemical properties such as
      the binding mechanism and band offset for single-wall zigzag nanotubes on InAs.
      While the tubes maintain their structural and electronic integrity, binding
      energies as large as 0.4 eV per site are obtained. Except for semiconducting
      tubes on the polar surfaces, an approximate universal band alignment is also
      obtained. The exception is due to large surface dipoles. In fact, polar (111) and
      (1;1;1;) surfaces have opposite dipoles that cause autodoping of a (14,0) tube to
      the n and the p type, respectively, without actual dopant.

PMID- 15169172
TI  - Surfactant-induced surface freezing at the alkane-water interface.
AB  - Long-chain alkanes exhibit surface freezing at the alkane-air but not the alkane
      water interface. Ellipsometry and surface tensiometry are used to show that a
      simple cationic surfactant, hexadecyltrimethylammonium bromide (CTAB), can induce
      surface freezing at the tetradecane-water interface even when present in mole
      fractions as low as 0.1. The surface-freezing temperature T(s) is a linear
      function of the interfacial excess of CTAB. The excess surface entropy below
      T(s), S(sigma)=-0.76+/-0.02 mJ K-1 m(-2), is consistent with a rotator phase.
      Ellipsometry provides strong evidence for a frozen monolayer in which the chains
      are oriented near the surface normal.

PMID- 15169174
TI  - Nonunitary spin-charge separation in a one-dimensional fermion gas.
AB  - In this Letter we report exact results on the infrared asymptotics of the one
      particle dynamical correlation function of the gas of impenetrable spin 1/2
      fermions at infinitesimal temperature. The correlation function shows signs of
      spin-charge separation with scaling behavior in the charge part and exponential
      decay as a function of the space coordinate in the spin part. Surprisingly, the
      anomalous dimensions in the charge part do not correspond to any unitary
      conformal field theory. We find that the fermion spectral weight has a power law
      divergency at low energy with the anomalous exponent -1/2.

PMID- 15169173
TI  - "Hot-atom" O2 dissociation and oxide nucleation on Al(111).
AB  - We propose an atomistic model for the nucleation of aluminum oxide on the Al(111)
      surface derived from first principles molecular dynamics simulations. The process
      begins with the dissociative adsorption of O2 molecules on the metal surface,
      which occurs via a "hot-atom" mechanism driven by the partial filling of the
      sigma* antibonding molecular orbital of O2. During the subsequent hyperthermal
      motion, O atoms can be spontaneously incorporated underneath the topmost Al
      surface layer, initiating the nucleation of the oxide far below the saturation
      coverage of one (1 x 1) O adlayer.

PMID- 15169175
TI  - Angular distribution of photoluminescence as a probe of bose condensation of
      trapped excitons.
AB  - Recent experiments on two-dimensional exciton systems have shown that excitons
      collect in shallow in-plane traps. We find that Bose condensation in a trap
      results in a dramatic change of the exciton photoluminescence (PL) angular
      distribution. The long-range coherence of the condensed state gives rise to a
      sharply focused peak of radiation in the direction normal to the plane. By
      comparing the PL profile with and without Bose condensation, we provide a simple
      diagnostic for the existence of a Bose condensate. The PL peak has strong
      temperature dependence due to the thermal order parameter phase fluctuations
      across the system. The angular PL distribution can also be used for imaging
      vortices in the trapped condensate. Vortex phase spatial variation leads to
      destructive interference of PL radiation in certain directions, creating nodes in
      the PL distribution that imprint the vortex configuration.

PMID- 15169176
TI  - Mott transition and suppression of orbital fluctuations in orthorhombic 3d1
      perovskites.
AB  - Using t(2g) Wannier functions, a low-energy Hamiltonian is derived for
      orthorhombic 3d(1) transition-metal oxides. Electronic correlations are treated
      with a new implementation of dynamical mean-field theory for noncubic systems.
      Good agreement with photoemission data is obtained. The interplay of correlation
      effects and cation covalency (GdFeO3-type distortions) is found to suppress
      orbital fluctuations in LaTiO3 and even more in YTiO3, and to favor the
      transition to the insulating state.

PMID- 15169178
TI  - Observation of "partial coherence" in an Aharonov-Bohm interferometer with a
      quantum dot.
AB  - We report experiments on the interference through spin states of electrons in a
      quantum dot (QD) embedded in an Aharonov-Bohm (AB) interferometer. We have picked
      up a spin-pair state, for which the environmental conditions are ideally similar.
      The AB amplitude is traced in a range of gate voltage that covers the pair. The
      behavior of the asymmetry in the amplitude around the two Coulomb peaks agrees
      with the theoretical prediction that the spin-flip process in a QD is related to
      the quantum dephasing of electrons. These results constitute evidence of "partial
      coherence" due to an entanglement of spins in the QD and in the interferometer.

PMID- 15169179
TI  - Are current-induced forces conservative?
AB  - The expression for the force on an ion in the presence of current can be derived
      from first principles without any assumption about its conservative character.
      However, energy functionals have been constructed that indicate that this force
      can be written as the derivative of a potential. On the other hand, there exist
      specific arguments that strongly suggest the contrary. We propose physical
      mechanisms that invalidate such arguments and demonstrate their existence with
      first-principles calculations. While our results do not constitute a formal
      resolution to the fundamental question of whether current-induced forces are
      conservative, they represent a substantial step forward in this direction.

PMID- 15169177
TI  - Transition between quantum states in a parallel-coupled double quantum dot.
AB  - Strong electron and spin correlations in a double quantum dot (DQD) can give rise
      to different quantum states. We observe a continuous transition from a Kondo
      state exhibiting a single-peak Kondo resonance to another exhibiting a double
      peak by increasing the interdot coupling (t) in a parallel-coupled DQD. The
      transition into the double-peak state provides evidence for spin entanglement
      between the excess electrons on each dot. Toward the transition, the peak
      splitting merges and becomes substantially smaller than t because of strong
      Coulomb effects. Our device tunability bodes well for future quantum computation
      applications.

PMID- 15169181
TI  - Coulomb blockade of proximity effect at large conductance.
AB  - We consider the proximity effect in a normal dot coupled to a bulk
      superconducting reservoir by the tunnel contact with large normal conductance.
      Coulomb interaction in the dot suppresses the proximity minigap induced in the
      normal part of the system. We find exact expressions for the thermodynamic and
      tunneling minigaps as functions of the junction's capacitance. The tunneling
      minigap interpolates between its proximity-induced value in the regime of weak
      Coulomb interaction to the Coulomb gap in the regime of strong interaction. In
      the intermediate case a nonuniversal two-step structure of the tunneling density
      of states is predicted. The charge quantization in the dot is also studied.

PMID- 15169182
TI  - Nondemolition measurements of a single quantum spin using Josephson oscillations.
AB  - We consider a single localized spin-1/2 between the singlet superconducting leads
      of a Josephson junction (e.g., a superconducting STM). For the spin subject to a
      dc magnetic field B parallel z, we study the spin dynamics and the possibility to
      measure the spin state via transport through the junction embedded in a
      dissipative circuit. Turning on the tunneling or a voltage bias induces
      oscillations of the Josephson current, with an amplitude sensitive to the initial
      value of the z component of the spin, S(z)=+/-1/2. At low temperatures, when
      effects of quasiparticles are negligible, this procedure realizes a quantum
      nondemolition measurement of S(z).

PMID- 15169180
TI  - Frequency scales for current statistics of mesoscopic conductors.
AB  - We calculate the third cumulant of current in a chaotic cavity with contacts of
      arbitrary transparency as a function of frequency. Its frequency dependence
      drastically differs from that of the conventional noise. In addition to a
      dispersion at the inverse RC time characteristic of charge relaxation, it has a
      low-frequency dispersion at the inverse dwell time of electrons in the cavity.
      This effect is suppressed if both contacts have either large or small
      transparencies.

PMID- 15169183
TI  - Staggered flux vortices and the superconducting transition in the layered
      cuprates.
AB  - We propose an effective model for the superconducting transition in the high-T(c)
      cuprates motivated by the SU(2) gauge theory approach. In addition to variations
      of the superconducting phase we allow for local admixture of staggered flux
      order. This leads to an unbinding transition of vortices with a staggered flux
      core that are energetically preferable to conventional vortices. Based on
      parameter estimates for the two-dimensional t-J model we argue that the staggered
      flux vortices provide a way to understand a phase with a moderate density of
      mobile vortices over a large temperature range above T(c) that yet exhibits
      otherwise normal transport properties. This picture is consistent with the large
      Nernst signal observed in this region.

PMID- 15169184
TI  - Test of the Wiedemann-Franz law in an optimally doped cuprate.
AB  - We present a study of heat and charge transport in Bi(2+x)Sr(2-x)CuO(6+delta)
      focused on the size of the low-temperature linear term of the thermal
      conductivity at optimal-doping level. In the superconducting state, the magnitude
      of this term implies a d-wave gap with an amplitude close to what has been
      reported. In the normal state, recovered by the application of a magnetic field,
      measurement of this term and residual resistivity yields a Lorenz number
      L=kappa(N)rho(0)/T=1.3+/-0.2L(0). The departure from the value expected by the
      Wiedemann-Franz law is thus slightly larger than our estimated experimental
      resolution.

PMID- 15169185
TI  - Thermopower induced by a supercurrent in superconductor-normal-metal structures.
AB  - We examine the thermopower Q of a mesoscopic normal-metal (N) wire in contact
      with superconducting (S) segments and show that even with electron-hole symmetry
      Q may become finite due to the presence of supercurrents. Moreover, we show how
      the dominant part of Q can be directly related to the equilibrium supercurrents
      in the structure. In general, a finite thermopower appears both between the N
      reservoirs and the superconductors and between the N reservoirs themselves. The
      latter, however, strongly depends on the geometrical symmetry of the structure.

PMID- 15169186
TI  - Competition between helimagnetism and commensurate quantum spin correlations in
      LiCu2O2.
AB  - Neutron diffraction and bulk measurements are used to determine the nature of the
      low-temperature ordered state in LiCu2O2, a S=1/2 spin-chain compound with
      competing interactions. The spin structure is found to be helimagnetic, with a
      propagation vector (0.5,zeta,0), zeta=0.174. The nearest-neighbor exchange
      constant and frustration ratio are estimated to be J(1)=5.8 meV and
      J(2)/J(1)=0.29, respectively. For idealized quantum spin chains, these parameter
      values would signify a gapped spin-liquid ground state with commensurate spin
      correlations. The observed temperature dependence of the magnetic propagation
      vector in LiCu2O2 is attributed to a competition between incommensurate
      helimagnetism in the classical spin model and commensurability in the quantum
      case. It is also proposed that long-range ordering in LiCu2O2 is facilitated by
      intrinsic nonstoichiometry.

PMID- 15169187
TI  - Ordering and excitations in the field-induced magnetic phase of Cs3Cr2Br9.
AB  - Field-induced magnetic order has been investigated in detail in the interacting
      spin 3/2 dimer system Cs3Cr2Br9. Elastic and inelastic neutron scattering
      measurements were performed up to H=6 T, well above the critical field H(c1)
      approximately 1.5 T. The ordering displays incommensurabilities and a large
      hysteresis before a commensurate structure is reached. This structure is fully
      determined. Surprisingly, the lowest excitation branch never closes. Above H(c1),
      the gap increases slowly with the field. An analysis in terms of projected
      pseudospins is given.

PMID- 15169188
TI  - Griffiths phase in diluted magnetic semiconductors.
AB  - We study the effects of disorder in the vicinity of the ferromagnetic transition
      in a diluted magnetic semiconductor in the strongly localized regime. We derive
      an effective polaron Hamiltonian, which leads to the Griffiths phase above the
      ferromagnetic transition point. The Griffiths-McCoy effects yield nonperturbative
      contributions to the dynamic susceptibility. We explicitly derive the long-time
      susceptibility, which has a pseudoscaling form, with the dynamic critical
      exponent being expressed through the percolation indices.

PMID- 15169189
TI  - Time-resolved fluorescence of carbon nanotubes and its implication for radiative
      lifetimes.
AB  - The temporal evolution of fluorescence from isolated single-wall carbon nanotubes
      (SWNTs) has been investigated using optical Kerr gating. The fluorescence
      emission is found to decay on a time scale of 10 ps. This fast relaxation arises
      from nonradiative processes, the existence of which explains the relatively low
      observed fluorescence efficiency in isolated SWNTs. From the measured decay rate
      and a determination of fluorescence quantum efficiency, we deduce a radiative
      lifetime of 110 ns.

PMID- 15169190
TI  - Femtosecond study of the interplay between excitons, trions, and carriers in
      (Cd,Mn)Te quantum wells.
AB  - We study the absorption by neutral excitons and positively charged excitons
      (trions) following a femtosecond, circularly polarized, resonant pump pulse.
      Three populations are involved: free holes, excitons, and trions, all exhibiting
      transient spin polarization. In particular, a polarization of the gas of free
      holes is created by the formation of trions. The evolution of these populations
      is described, including spin flip and trion formation. We evaluate the
      contributions of phase space filling and spin-dependent screening. We propose a
      new explanation of the oscillator strength stealing phenomena observed in doped
      quantum wells, based on the screening of neutral excitons by charge carriers. We
      have also found that binding holes into charged excitons excludes them from the
      interaction with the rest of the system, so that oscillator strength stealing is
      partially blocked.

PMID- 15169191
TI  - Generation and characterization of Werner states and maximally entangled mixed
      states by a universal source of entanglement.
AB  - We present a novel technique for generating two-photon polarization mixed states
      of any structure, which is based on the peculiar spatial characteristics of a
      high brilliance source of entangled pairs. Werner states and maximally entangled
      mixed states, two well-known families of mixed states important for quantum
      information, have been created and fully characterized by this technique. We have
      also investigated and tested the nonlocal properties of these states.

PMID- 15169192
TI  - Efficient decomposition of quantum gates.
AB  - Optimal implementation of quantum gates is crucial for designing a quantum
      computer. We consider the matrix representation of an arbitrary multiqubit gate.
      By ordering the basis vectors using the Gray code, we construct the quantum
      circuit which is optimal in the sense of fully controlled single-qubit gates and
      yet is equivalent with the multiqubit gate. In the second step of the
      optimization, superfluous control bits are eliminated, which eventually results
      in a smaller total number of the elementary gates. In our scheme the number of
      controlled NOT gates is O(4(n)) which coincides with the theoretical lower bound.

PMID- 15169193
TI  - Tripartite quantum state sharing.
AB  - We demonstrate a multipartite protocol to securely distribute and reconstruct a
      quantum state. A secret quantum state is encoded into a tripartite entangled
      state and distributed to three players. By collaborating, any two of the three
      players can reconstruct the state, while individual players obtain nothing. We
      characterize this (2,3) threshold quantum state sharing scheme in terms of
      fidelity, signal transfer, and reconstruction noise. We demonstrate a fidelity
      averaged over all reconstruction permutations of 0.73+/-0.04, a level achievable
      only using quantum resources.

PMID- 15169194
TI  - Magnetic phase shifter for superconducting qubits.
AB  - We have designed and investigated a contactless magnetic phase shifter for flux
      based superconducting qubits. The phase shifter is realized by placing a
      perpendicularly magnetized dot at the center of a superconducting loop. The flux
      generated by this magnetic dot gives rise to an additional shielding current in
      the loop and induces a phase shift. By modifying the parameters of the dot an
      arbitrary phase shift can be generated in the loop. This magnetic phase shifter
      can, therefore, be used as an external current source in superconducting
      circuits, as well as a suitable tool to study fractional Josephson vortices.

PMID- 15169195
TI  - Distinguishability and indistinguishability by local operations and classical
      communication.
AB  - It is well known that orthogonal quantum states can be distinguished perfectly.
      However, if we assume that these orthogonal quantum states are shared by
      spatially separated parties, the distinguishability of these shared quantum
      states may be completely different. We show that a set of linearly independent
      quantum states [formula: see text] where U(m,n) are generalized Pauli matrices,
      cannot be discriminated deterministically or probabilistically by local
      operations and classical communication. On the other hand, any l maximally
      entangled states from this set are locally distinguishable if l(l-1)< or =2d. The
      explicit projecting measurements are obtained to locally discriminate these
      states. As an example, we show that four Werner states are locally
      indistinguishable.

PMID- 15169196
TI  - Exponential speedup with a single bit of quantum information: measuring the
      average fidelity decay.
AB  - We present an efficient quantum algorithm to measure the average fidelity decay
      of a quantum map under perturbation using a single bit of quantum information.
      Our algorithm scales only as the complexity of the map under investigation. Thus
      for those maps admitting an efficient gate decomposition, it provides an
      exponential speedup over known classical procedures. Fidelity decay is important
      in the study of complex dynamical systems, where it is conjectured to be a
      signature of eigenvector statistics. Our result also illustrates the role of
      chaos in the process of decoherence.

PMID- 15169197
TI  - Anomalous diffusion probes microstructure dynamics of entangled F-actin networks.
AB  - We study the thermal motion of colloidal tracer particles in entangled actin
      filament (F-actin) networks, where the particle radius is comparable to the mesh
      size of the F-actin network. In this regime, the ensemble-averaged mean-squared
      displacement of the particles is proportional to tau(gamma), where 0<gamma<1 from
      0.1<tau<100 s and depends only on the ratio of the probe radius to mesh size. By
      directly imaging hundreds of particles over 20 min, we determine this anomalous
      subdiffusion is due to the dynamics of infrequent and large jumps particles make
      between distinct pores in the network.

PMID- 15169198
TI  - Dephasing of solid-state qubits at optimal points.
AB  - Motivated by recent experiments with Josephson-junction circuits, we analyze the
      influence of various noise sources on the dynamics of two-level systems at
      optimal operation points where the linear coupling to low-frequency fluctuations
      is suppressed. We study the decoherence due to nonlinear (quadratic) coupling,
      focusing on the experimentally relevant 1/f and Ohmic noise power spectra. For
      1/f noise strong higher-order effects influence the evolution.

PMID- 15169199
TI  - Nonvolatile memory with multilevel switching: a basic model.
AB  - There is a current upsurge in research on nonvolatile two-terminal resistance
      random access memory (RRAM) for next generation electronic applications. The RRAM
      is composed of a simple sandwich of a semiconductor with two metal electrodes. We
      introduce here an initial model for RRAM with the assumption that the
      semiconducting part has a nonpercolating domain structure. We solve the model
      using numerical simulations and the basic carrier transfer mechanism is unveiled
      in detail. Our model captures three key features observed in experiments:
      multilevel switchability of the resistance, its memory retention, and hysteretic
      behavior in the current-voltage curve.

PMID- 15169200
TI  - Velocity and hierarchical spread of epidemic outbreaks in scale-free networks.
AB  - We study the effect of the connectivity pattern of complex networks on the
      propagation dynamics of epidemics. The growth time scale of outbreaks is
      inversely proportional to the network degree fluctuations, signaling that
      epidemics spread almost instantaneously in networks with scale-free degree
      distributions. This feature is associated with an epidemic propagation that
      follows a precise hierarchical dynamics. Once the highly connected hubs are
      reached, the infection pervades the network in a progressive cascade across
      smaller degree classes. The present results are relevant for the development of
      adaptive containment strategies.

PMID- 15169201
TI  - Hierarchy measures in complex networks.
AB  - Using each node's degree as a proxy for its importance, the topological hierarchy
      of a complex network is introduced and quantified. We propose a simple dynamical
      process used to construct networks which are either maximally or minimally
      hierarchical. Comparison with these extremal cases as well as with random scale
      free networks allows us to better understand hierarchical versus modular features
      in several real-life complex networks. For random scale-free topologies the
      extent of topological hierarchy is shown to smoothly decline with gamma, the
      exponent of a degree distribution, reaching its highest possible value for
      gamma</=2 and quickly approaching zero for gamma>3.

PMID- 15169202
TI  - Comment on "Higher surface energy of free nanoparticles".

PMID- 15169204
TI  - Exact pairing correlations for one-dimensionally trapped fermions with stochastic
      mean-field wave functions.
AB  - The canonical thermodynamic properties of a one-dimensional system of interacting
      spin-1/2 fermions with an attractive zero-range pseudopotential are investigated
      within an exact approach. The density operator is evaluated as the statistical
      average of dyadics formed from a stochastic mean-field propagation of independent
      Slater determinants. For a harmonically trapped Fermi gas and for fermions
      confined in a 1D-like torus, we observe the transition to a quasi-BCS state with
      Cooper-like momentum correlations and an algebraic long-range order. For a few
      trapped fermions in a rotating torus, a dominant superfluid component with
      quantized circulation can be isolated.

PMID- 15169206
TI  - Controlled vortex-sound interactions in atomic Bose-Einstein condensates.
AB  - The low temperature dynamics of a vortex in a trapped quasi-two-dimensional Bose
      Einstein condensate are studied quantitatively. Precession of an off-centered
      vortex in a dimple trap, embedded in a weaker harmonic trap, leads to the
      emission of sound in a dipolar radiation pattern. Sound emission and reabsorption
      can be controlled by varying the depth of the dimple. In a shallow dimple, the
      power emitted is proportional to the vortex acceleration-squared over the
      precession frequency, whereas for a deep dimple, periodic sound reabsorption
      stabilizes the vortex against radiation-induced decay.

PMID- 15169205
TI  - Superfluid transitions in bosonic atom-molecule mixtures near a Feshbach
      resonance.
AB  - We study bosonic atoms near a Feshbach resonance and predict that, in addition to
      standard normal and atomic superfluid phases, this system generically exhibits a
      distinct phase of matter: a molecular superfluid, where molecules are superfluid
      while atoms are not. We explore zero- and finite-temperature properties of the
      molecular superfluid (a bosonic, strong-coupling analog of a BCS superconductor),
      and study quantum and classical phase transitions between the normal, molecular
      superfluid, and atomic superfluid states.

PMID- 15169208
TI  - Tkachenko waves in rapidly rotating Bose-Einstein condensates.
AB  - We present a mean-field theory numerical study of Tkachenko waves of a vortex
      lattice in trapped atomic Bose-Einstein condenstates. Our results show remarkable
      qualitative and quantitative agreement with recent experiments at the Joint
      Institute for Laboratory Astrophysics. We extend our calculations beyond the
      conditions of the experiment, probing deeper into the incompressible regime where
      we find excellent agreement with analytical results. In addition, bulk
      excitations observed in the experiment are discussed.

PMID- 15169207
TI  - High temperature expansion applied to fermions near Feshbach resonance.
AB  - We show that, apart from a difference in scale, all of the surprising recently
      observed properties of a degenerate Fermi gas near a Feshbach resonance persist
      in the high temperature Boltzmann regime. In this regime, the Feshbach resonance
      is unshifted. By sweeping across the resonance, a thermal distribution of bound
      states (molecules) can be reversibly generated. Throughout this process, the
      interaction energy is negative and continuous. We also show that this behavior
      must persist at lower temperatures unless there is a phase transition as the
      temperature is lowered. We rigorously demonstrate universal behavior near the
      resonance.

PMID- 15169209
TI  - Entanglement interferometry for precision measurement of atomic scattering
      properties.
AB  - We report on a matter wave interferometer realized with entangled pairs of
      trapped 87Rb atoms. Each pair of atoms is confined at a single site of an optical
      lattice potential. The interferometer is realized by first creating a coherent
      spin superposition of the two atoms and then tuning the interstate scattering
      length via a Feshbach resonance. The selective change of the interstate
      scattering length leads to an entanglement dynamics of the two-particle state
      that can be detected in a Ramsey interference experiment. This entanglement
      dynamics is employed for a precision measurement of atomic interaction
      parameters. Furthermore, the interferometer allows us to separate lattice sites
      with one or two atoms in a nondestructive way.

PMID- 15169210
TI  - Collisionally induced transport in periodic potentials.
AB  - We study the transport of ultracold atoms in a tight optical lattice. For
      identical fermions the system is insulating under an external force while for
      bosonic atoms it is conducting. This reflects the different collisional
      properties of the particles and reveals the role of interparticle collisions in
      establishing a macroscopic transport in a perfectly periodic potential. Also in
      the case of fermions we can induce a transport by creating a collisional regime
      through the addition of bosons. We investigate the transport as a function of the
      collisional rate and observe a transition from a regime in which the mobility
      increases with increasing collisional rate to one in which it decreases. We
      compare our data with a theoretical model for electron transport in solids
      introduced by Esaki and Tsu.

PMID- 15169211
TI  - Manipulating small particles in mixtures far from equilibrium.
AB  - The motion of two interacting species of small particles, coupled differently to
      their environment, is studied both analytically and via numerical simulations. We
      find three ways of controlling the particle motion of one (passive) B species by
      means of another (active) A species: (i) dragging the target particles B by
      driving the auxiliary particles A, (ii) rectifying the motion of the B species on
      the asymmetric potential created by the A-B interactions, and (iii) dynamically
      modifying (pulsating) this potential by controlling the motion of the A
      particles. This allows easy control of the magnitude and direction of the
      velocity of the target particles by changing the ac drive(s).

PMID- 15169212
TI  - Apparent hysteresis in a driven system with self-organized drag.
AB  - The motion of extended defects in materials is often resisted by interaction with
      diffusing impurities. The defect undergoes a transition from slow to fast
      migration, or vice versa. This transition is commonly hysteretic, with the defect
      jumping back and forth between these kinetic states. We explore such hysteresis
      within a kinetic Monte Carlo simulation. After identifying the slow variables, we
      construct an effective potential that quantitatively describes the stable and
      metastable states of the system (a bifurcation diagram) and the kinetics of the
      transitions between these. This description provides a means to determine whether
      hysteresis will be observed in a particular simulation and the detailed nature of
      this hysteresis (switching times).

PMID- 15169213
TI  - Scaling behavior in a stochastic self-gravitating system.
AB  - A system of stochastic differential equations for the velocity and density of
      classical self-gravitating matter is investigated by means of the field theoretic
      renormalization group. The existence of two types of large-scale scaling
      behavior, associated with physically admissible fixed points of the
      renormalization-group equations, is established. Their regions of stability are
      identified and the corresponding scaling dimensions are calculated in the one
      loop approximation (first order of the epsilon expansion). The velocity and
      density fields have independent scaling dimensions. Our analysis supports the
      importance of the rotational (nonpotential) components of the velocity field in
      the formation of those scaling laws.

PMID- 15169214
TI  - Experimental demonstration of a classical analog to quantum noise cancellation
      for use in gravitational wave detection.
AB  - We present results that are a classical analog to quantum noise cancellation. It
      is possible to breach the standard quantum limit in an interferometer by the use
      of squeezing to correlate orthogonal quadratures of quantum noise, causing their
      effects on the resulting sensitivity to cancel. A laser beam incident on a Fabry
      Perot cavity was imprinted with classical, correlated noise in the same
      quadratures that cause shot noise and radiation pressure noise. Couplings between
      these quadratures due to a movable mirror, sensitive to radiation pressure, cause
      the excess classical noise to cancel. This cancellation was shown to improve the
      signal to noise ratio of an injected signal by approximately a factor of 10.

PMID- 15169215
TI  - Dirac neutrino masses with planck scale lepton number violation.
AB  - It is shown how pure Dirac neutrino masses can naturally occur at low energies
      even in the presence of Planck scale lepton number violation. In a 5D setting
      this is achieved by explicitly breaking the lepton number on the Planck brane
      while the right-handed neutrino is localized on the TeV brane. A small wave
      function overlap then naturally leads to a small Dirac Yukawa coupling. In the 4D
      dual description the right-handed neutrino is identified as a composite CFT bound
      state and lepton number violation is highly suppressed by CFT operators with
      large anomalous dimensions.

PMID- 15169216
TI  - Weakened constraints from b-->sgamma on supersymmetry flavor mixing due to next
      to-leading-order corrections.
AB  - We examine the process B-->X(s)gamma in minimal supersymmetry (SUSY) with general
      squark flavor mix-ings. We include all relevant next-to-leading order (NLO) QCD
      corrections and dominant NLO SUSY effects from the gluino. We find that gluino
      squark corrections to down-type quark masses induce large NLO corrections to the
      dominant Wilson coefficients whose size is often similar to those at LO, es
      pecially at large tan(beta. For micro>0, destructive interference and suppression
      by the renormalization group running lead to a "focusing effect" of reducing the
      size of gluino corrections to the branching ratio, and also of reducing the LO
      sensitivity to flavor mixings among squarks. Constraints from B(B-->X(s)gamma) on
      the SUSY-breaking scale can become significantly weakened relative to the minimal
      flavor violation case, even, at large tan(beta, for small flavor mixings. The
      case of micro<0 also becomes allowed.

PMID- 15169218
TI  - Bs and Ds decay constants in three-flavor lattice QCD.
AB  - Capitalizing on recent advances in lattice QCD, we present a calculation of the
      leptonic decay constants f(B(s)) and f(D(s)) that includes effects of one strange
      sea quark and two light sea quarks via an improved staggered action. By shedding
      the quenched approximation and the associated lattice scale uncertainty, lattice
      QCD greatly increases its predictive power. Nonrelativistic QCD is used to
      simulate heavy quarks with masses between 1.5m(c) and m(b). We arrive at the
      following results: f(B(s))=260+/-7+/-26+/-8+/-5 and f(D(s))=290+/-20+/-29+/-29+/
      6 MeV. The first quoted error is the statistical uncertainty, and the rest
      estimate the sizes of higher order terms neglected in this calculation. All of
      these uncertainties are systematically improvable by including another order in
      the weak coupling expansion, the nonrelativistic expansion, or the Symanzik
      improvement program.

PMID- 15169219
TI  - Simplified test of universality in lattice QCD.
AB  - A simplified test of universality in lattice QCD is performed by analytically
      evaluating the continuous Euclidean time limits of various lattice fermion
      determinants, both with and without a Wilson term to lift the fermion doubling on
      the Euclidean time axis, and comparing them with each other and with the zeta
      regularized fermion determinant in the continuous time-lattice space setting. The
      determinant relations expected from universality considerations are found to be
      violated by a certain gauge field-dependent factor; i.e., we uncover a
      "universality anomaly." The physical significance, or lack thereof, of this
      factor is a delicate question that remains to be settled.

PMID- 15169220
TI  - Ambiguities in the up-quark mass.
AB  - It has long been known that no physical singularity is encountered as up-quark
      mass is adjusted from small positive to negative values as long as all other
      quarks remain massive. This is tied to an additive ambiguity in the definition of
      the quark mass. This calls into question the acceptability of attempts to solve
      the strong CP problem via a vanishing mass for the lightest quark.

PMID- 15169221
TI  - Traces of thermalization from p(t) fluctuations in nuclear collisions.
AB  - Scattering of particles produced in high energy nuclear collisions can wrestle
      the system into a state near local thermal equilibrium. I illustrate how
      measurements of the centrality dependence of the mean transverse momentum and its
      fluctuations can exhibit this thermalization.

PMID- 15169222
TI  - Is the nuclear spin-orbit interaction changing with neutron excess?
AB  - The difference in the energies of the lowest states corresponding to the two
      nodeless single-particle orbitals outside the Z=50 closed proton shell, h(11/2)
      and g(7/2), increases with neutron excess. We have measured the Sn(alpha,t)
      reaction for all seven stable even Sn isotopes and found that the spectroscopic
      factors are constant for these two states, confirming their characterization as
      single-particle states. The trend in energies is consistent with a decrease in
      the nuclear spin-orbit interaction. A similar trend, also suggesting a decreasing
      spin-orbit splitting, is seen in the energies of the neutron single-particle
      states outside the N=82 core, i(13/2) and h(9/2).

PMID- 15169217
TI  - Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.
AB  - The anomalous magnetic moment of the negative muon has been measured to a
      precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron.
      This result is based on data collected in 2001, and is over an order of magnitude
      more precise than the previous measurement for the negative muon. The result
      a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is
      statistical and the second is systematic, is consistent with previous
      measurements of the anomaly for the positive and the negative muon. The average
      of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10)
      (0.5 ppm).

PMID- 15169223
TI  - Fully differential cross sections for photo-double-ionization of D2.
AB  - We report the first kinematically complete study of the four-body fragmentation
      of the D2 molecule following absorption of a single photon. For equal energy
      sharing of the two electrons and a photon energy of 75.5 eV, we observed the
      relaxation of one of the selection rules valid for He photo-double-ionization and
      a strong dependence of the electron angular distribution on the orientation of
      the molecular axis. This effect is reproduced by a model in which a pair of
      photoionization amplitudes is introduced for the light polarization parallel and
      perpendicular to the molecular axis.

PMID- 15169224
TI  - Generation of coherent soft-X-ray radiation extending far beyond the titanium L
      edge.
AB  - Coherent soft-x-ray radiation up to photon energies of 700 eV is obtained by
      focusing several-mJ, 10-fs near infrared laser pulses into a He gas jet. The
      observed nearly constant photon yield over several hundred eVs may be attributed
      to nonadiabatic self-phase matching, originating from a substantial ionization
      within a fraction of the optical cycle of the driving laser pulse.

PMID- 15169225
TI  - Two-level systems with relaxation.
AB  - A method is presented for the coherent control of two-level systems when T2
      relaxation is significant. The Bloch equations are rewritten as an equation of
      motion of the stereographic projection, Gamma, of the spin vector. This allows a
      Schur-type iteration used for the design of shaped pulses in magnetic resonance
      and coherent optics to be extended to include the effect of T2. In general, the
      effect of T2 on Gamma cannot be completely compensated for, although in practice
      it can be to a high degree. An example is presented of a driving field that
      produces a coherent superposition (no on-diagonal elements of the density matrix)
      over a chosen band of frequencies, in the presence of relaxation.

PMID- 15169228
TI  - Interaction of NH(X3Sigma-) molecules with rubidium atoms: implications for
      sympathetic cooling and the formation of extremely polar molecules.
AB  - The Rb-NH interaction is investigated as a prototype for interactions between
      alkali-metal atoms and stable molecules. For spin-aligned Rb and NH that interact
      on a quartet surface (4A"), the interaction is relatively weak, with a well depth
      of 0.078 eV. However, there are also doublet surfaces of ion-pair character that
      are very much deeper (well depth 1.372 eV). They may be important for atom
      molecule collision rates and offer the possibility of forming strongly dipolar
      molecules by photoassociation. Similar deeply bound ion-pair states are likely to
      exist for other alkali atom-molecule pairs.

PMID- 15169227
TI  - Coherence properties of guided-atom interferometers.
AB  - We present a detailed theoretical investigation of the coherence properties of
      beam splitters and Mach-Zehnder interferometers for guided neutral atoms. We show
      that such a setup permits coherent wave packet splitting and leads to the
      appearance of interference fringes for both single-mode and thermal input states,
      evidencing thus the robustness of the interferometer.

PMID- 15169226
TI  - Intense-laser-field ionization of molecular hydrogen in the tunneling regime and
      its effect on the vibrational excitation of H2+.
AB  - H2 molecules were ionized by Ti:sapphire (45 fs, 800 nm) and Nd-doped yttrium
      aluminum garnet lasers (6 ns, 1064 nm). The relative populations of the
      vibrational levels of the H+2 ions were determined and found to be concentrated
      in the lowest vibrational levels. Tunneling ionization calculations with exact
      field-modified potential curves reproduce the experimental results. The reason
      for the departure from conventional Franck-Condon-like distributions is the rapid
      variation of the ionization rate with internuclear distance.

PMID- 15169229
TI  - Extremely stable metal-encapsulated AlPb10+ and AlPb12+ clusters: mass
      spectrometric discovery and density functional theory study.
AB  - We report the experimental discovery of extremely stable metal-encapsulated
      superatom clusters of a group IVA element: AlPb+10 and AlPb+12. Ab initio density
      functional geometry optimizations at the B3LYP/LANL2DZ level result in a perfect
      icosahedron with an exceptionally large HOMO-LUMO gap of 3.1 eV for AlPb+12, and
      a related structure with D(4d) symmetry for AlPb+10, with a HOMO-LUMO gap of 2.6
      eV. Their high stability is attributed to the reinforcing influence of the most
      favorable closed-packed structure and optimally filled electron shells.

PMID- 15169230
TI  - From nearly tilted waves to cavity phase solitons in broad area lasers with
      squeezed vacuum.
AB  - Phase domains and phase solitons in two-level amplifying media damped by a
      squeezed vacuum are predicted for the first time. Two different types of pattern
      formation are found depending on the relative value of the cavity detuning to the
      squeezed parameter: the usual one in lasers via a supercritical Hopf bifurcation
      and a new one via pitchfork bifurcation.

PMID- 15169232
TI  - Computational lens for the near field.
AB  - A method is presented to reconstruct the structure of a scattering object from
      data acquired with a photon scanning tunneling microscope. The data may be
      understood to form a Gabor type near-field hologram and are obtained at a
      distance from the sample where the field is defocused and normally
      uninterpretable. Object structure is obtained by the solution of the inverse
      scattering problem within the accuracy of a perturbative, two-dimensional model
      of the object.

PMID- 15169231
TI  - Experimental observation of discrete modulational instability.
AB  - We report the first experimental observation of modulation instability in a
      discrete optical nonlinear array.

PMID- 15169233
TI  - Real-time construction of optimized predictors from data streams.
AB  - A new approach to the construction and optimization of local models is proposed
      in the context of data streams, that is, unlimited sources of data where the
      utilization of all observations is impractical. Real-time revision of the
      learning set allows selective coverage of regions in state space which contribute
      most to reconstructing the underlying dynamical system.

PMID- 15169234
TI  - Fluidized granular medium as an instance of the fluctuation theorem.
AB  - We study the statistics of the power flux into a collection of inelastic beads
      maintained in a fluidized steady state by external mechanical driving. The power
      shows large fluctuations, including frequent large negative fluctuations, about
      its average value. The relative probabilities of positive and negative
      fluctuations in the power flux are in close accord with the fluctuation theorem
      of Gallavotti and Cohen, even at time scales shorter than those required by the
      theorem. We also compare an effective temperature that emerges from this analysis
      to the kinetic granular temperature.

PMID- 15169235
TI  - Mixing by polymers: experimental test of decay regime of mixing.
AB  - By using high molecular weight fluorescent passive tracers with different
      diffusion coefficients and by changing the fluid velocity we study the dependence
      of a characteristic mixing length on the Peclet number, Pe, which controls the
      mixing efficiency. The mixing length is found to be related to Pe by a power law,
      L(mix) proportional, variant Pe0.26+/-0.01, and increases faster than expected
      for an unbounded chaotic flow. The role of the boundaries in the mixing length
      abnormal growth is clarified. The experimental findings are in good quantitative
      agreement with recent theoretical predictions.

PMID- 15169237
TI  - Study of hot electrons by measurement of optical emission from the rear surface
      of a metallic foil irradiated with ultraintense laser pulse.
AB  - Hot electrons and optical emission are measured from the rear surface of a
      metallic foil. The spectra of the optical emission in the near infrared region
      have a sharp spike around the wavelength of the incident laser pulse. The optical
      emission is ascribed to coherent transition radiation due to microbunching in the
      hot electron beam. It is found that the optical emission closely correlates with
      the hot electrons accelerated in resonance absorption.

PMID- 15169236
TI  - Observation of multipactor in an alumina-based dielectric-loaded accelerating
      structure.
AB  - We report a new regime of single-surface multipactor that was observed during
      high-power testing of an 11.424-GHz alumina-based dielectric-loaded accelerating
      structure. Previous experimental observations of single-surface multipactor on a
      dielectric occurred in cases for which the rf electric field was tangential and
      the rf power flow was normal to the dielectric surface (such as on rf windows)
      and found that the fraction of power absorbed at saturation is approximately 1%,
      independent of the incident power. In this new regime, in which strong normal and
      tangential rf electric fields are present and the power flow is parallel to the
      surface, the fraction of power absorbed at saturation is an increasing function
      of the incident power, and more than half of the incident power can be absorbed.
      A simple model is presented to explain the experimental results.

PMID- 15169238
TI  - New paradigm for the isotope scaling of plasma transport paradox.
AB  - Most tokamak experimental results [Nucl. Fusion 33, 1205 (1993)]] and basic
      physics experiments [Phys. Rev. Lett. 89, 095001 (2002)]] in the Columbia Linear
      Machine indicate dependence of the ion thermal conductivity on the isotopic mass
      close to chi( perpendicular ) approximately A(-0.5)(i), i.e., inverse gyro-Bohm.
      This is in stark contradiction to most present theoretical models predicting Bohm
      (A(0)(i)) or gyro-Bohm (A(0.5)(i)) scaling. A series of experiments designed to
      explore the physics basis of this scaling appears to lead to a new model for this
      scaling based on 3-wave coupling of two ion temperature gradient radial harmonics
      and an ion acoustic wave.

PMID- 15169239
TI  - Computations of intermittent transport in scrape-off layer plasmas.
AB  - Two-dimensional fluid simulations of interchange turbulence for geometry and
      parameters relevant for the scrape-off layer of magnetized plasmas are presented.
      The computations, which have distinct plasma production and loss regions, reveal
      bursty ejection of particles and heat from the bulk plasma in the form of blobs.
      These structures propagate far into the scrape-off layer where they are
      dissipated due to transport along open magnetic field lines. From single-point
      recordings it is shown that the blobs have asymmetric conditional wave forms and
      lead to positively skewed and flattened probability distribution functions. The
      radial propagation velocity may reach one-tenth of the sound speed. These results
      are in excellent agreement with recent experimental measurements.

PMID- 15169240
TI  - Role of flow shear in the ballooning stability of tokamak transport barriers.
AB  - A tokamak's confinement time is greatly increased by a transport barrier (TB), a
      region having a high pressure gradient and usually also a strongly sheared plasma
      flow. The pressure gradient in a TB can be limited by ideal magnetohydrodynamic
      instabilities with a high toroidal mode number n ("ballooning modes"). Previous
      studies in the limit n--> infinity showed that arbitrarily small (but nonzero)
      flow shears have a large stabilizing influence. In contrast, the more realistic
      finite n ballooning modes studied here are found to be insensitive to sub
      Alfvenic flow shears, provided the magnetic shear s approximately 1 (typical for
      TBs near the plasma's edge). However, for the lower magnetic shears that are
      associated with internal transport barriers, significantly lower flow shears will
      influence ballooning mode stability, and flow shear should be retained in the
      analysis of their stability.

PMID- 15169241
TI  - Efficient multi-keV X-ray sources from Ti-doped aerogel targets.
AB  - We have measured the production of hnu approximately 4.7 keV x rays from low
      density Ti-doped aerogel (rho approximately 3 mg/cc) targets at the OMEGA laser
      facility (University of Rochester), with the goal of maximizing x-ray output.
      Forty OMEGA beams (lambda(L)=0.351 microm) illuminated the two cylindrical faces
      of the target with a total power that ranged from 7 to 14 TW. The laser fully
      ionizes the target (n(e)/n(crit)</=0.1), and a laser-bleaching wave excites,
      supersonically, the high-Z emitter ions in the sample. Ti K-shell x-ray emission
      was spectrally resolved with a two-channel crystal spectrometer and also with a
      set of filtered aluminum x-ray diodes; both instruments provide absolute
      measurement of the multi-keV x-ray emission. We find between 40 and 260 J of
      output with 4.67</=hnu</=5.0 keV.

PMID- 15169242
TI  - Emittance measurements of a laser-wakefield-accelerated electron beam.
AB  - The transverse emittance of a relativistic electron beam generated by the
      interaction of a high-intensity laser with an underdense plasma has been measured
      with the "pepper-pot" method. For parameters pertaining to the forced laser
      wakefield regime, we have measured an emittance as low as (2.7+/-0.9) pi mm mrad
      for (55+/-2) MeV electrons. These measurements are consistent with 3D particle-in
      cell simulations of the experiment, which additionally show the existence of a
      relatively large halo around the beam core.

PMID- 15169243
TI  - Probing nanoscale dipole-dipole interactions by electric force microscopy.
AB  - We address the issue of dipole-dipole interaction measurements at the nanometer
      scale. Electric dipoles with tunable effective momentum in the range 10(3)-10(4)
      D are generated by charge injection in single silicon nanoparticles on a
      conductive substrate and probed by a spectroscopic electric force microscopy
      analysis. Weak dipole-dipole force gradients are measured and identified from
      their quadratic momentum dependence. The results suggest that dipolar
      interactions associated with atomic-scale charge displacements or molecules can
      be probed by noncontact atomic force microscopy.

PMID- 15169244
TI  - Dipole-dependent slip of Newtonian liquids at smooth solid hydrophobic surfaces.
AB  - We present atomic force microscopy observations of the "effective" slippage of
      various nonpolar and polar liquids on alkylsilane coated glass surfaces. For
      small contact angle nonpolar liquids, the slip length decreases as one approaches
      a wetting transition. However, for large contact angle polar liquids it is found
      that the slip length is primarily influenced by the dipole moment, rather than
      the wettability of the liquid for the surface, where the slip length decreases
      with increasing dipole moment.

PMID- 15169245
TI  - New alkali doped pillared carbon materials designed to achieve practical
      reversible hydrogen storage for transportation.
AB  - We propose a new generation of materials to maximize reversible H2 storage at
      room temperature and modest pressures (<20 bars). We test these materials using
      grand canonical Monte Carlo simulations with a first-principles-derived force
      field and find that the Li pillared graphene sheet system can take up 6.5 mass%
      of H2 (a density of 62.9 kg/m(3) at 20 bars and room temperature. This satisfies
      the DOE (Department of Energy) target of hydrogen-storage materials for
      transportation. We also suggest ways to synthesize these systems. In addition we
      show that Li-doped pillared single-wall nanotubes can lead to a hydrogen-storage
      capacity of 6.0 mass% and 61.7 kg/m(3) at 50 bars and room temperature storage,
      which is close to the DOE target.

PMID- 15169246
TI  - Hierarchical self-assembly of GaAs/AlGaAs quantum dots.
AB  - A novel structure containing self-assembled, unstrained GaAs quantum dots is
      obtained by combining solid-source molecular beam epitaxy and atomic-layer
      precise in situ etching. Photo-luminescence (PL) spectroscopy reveals light
      emission with very narrow inhomogeneous broadening and clearly resolved excited
      states at high excitation intensity. The dot morphology is determined by scanning
      probe microscopy and, combined with single band and eight-band k.p theory
      calculations, is used to interpret PL and single-dot spectra with no adjustable
      structural parameter.

PMID- 15169247
TI  - Long jump rates in surface diffusion: W on W(110).
AB  - We have reexamined the diffusion of W adatoms on W(110) using the field ion
      microscope. The diffusivity is in good agreement with previous results and
      reveals no unusual features, but from observations of the distribution of
      displacements, corrected for diffusion during temperature transients, we have for
      the first time been able to measure the temperature dependence of rates for
      nearest-neighbor and double jumps, as well as for vertical and horizontal
      transitions. Activation energies and frequency factors for all the long jumps are
      significantly larger than for single jumps, and a simple model is proposed to
      account for our observations.

PMID- 15169248
TI  - The optimal faucet.
AB  - The production of small fluid droplets relies on an instability of solutions to
      the Young-Laplace equation. We ask whether smaller droplets can be produced by
      changing the shape of the nozzle. At a given critical pressure, the circular
      nozzle actually produces the largest droplet. The droplet volume can be decreased
      by up to 18% using a triangular nozzle with stretched corners.

PMID- 15169249
TI  - Direct observation of high-temperature polaronic behavior in colossal
      magnetoresistive manganites.
AB  - The temperature dependence of the electronic and atomic structure of the colossal
      magnetoresistive oxides La1-xSrxMnO3 (x=0.3, 0.4) has been studied using core and
      valence level photoemission, x-ray absorption and emission, and extended x-ray
      absorption fine structure spectroscopy. A dramatic and reversible change of the
      electronic structure is observed on crossing the Curie temperature, including
      charge localization on and spin-moment increase of Mn, together with Jahn-Teller
      distortions, both signatures of polaron formation. Our data are also consistent
      with a phase-separation scenario.

PMID- 15169250
TI  - Co-occurrence of superparamagnetism and anomalous hall effect in highly reduced
      cobalt-doped rutile TiO2-delta films.
AB  - We report a detailed magnetic and structural analysis of highly reduced Co doped
      rutile TiO(2-delta) films displaying an anomalous Hall effect (AHE). The
      temperature and field dependence of magnetization, and transmission electron
      microscopy, clearly establish the presence of nanosized superparamagnetic cobalt
      clusters of approximately 8-10 nm size in the films at the interface. The co
      occurrence of superparamagnetism and AHE raises questions regarding the use of
      the AHE as a test of the intrinsic nature of ferromagnetism in diluted magnetic
      semiconductors.

PMID- 15169251
TI  - Multiple first-order metamagnetic transitions and quantum oscillations in
      ultrapure Sr3Ru2O7.
AB  - We present measurements on ultraclean single crystals of the bilayered ruthenate
      metal Sr3Ru2O7, which has a magnetic-field-tuned quantum critical point. Quantum
      oscillations of differing frequencies can be seen in the resistivity both below
      and above its metamagnetic transition. This frequency shift corresponds to a
      small change in the Fermi surface volume that is qualitatively consistent with
      the small moment change in the magnetization across the metamagnetic transition.
      Very near the metamagnetic field, unusual behavior is seen. There is a strong
      enhancement of the resistivity in a narrow field window, with a minimum in the
      resistivity as a function of temperature below 1 K that becomes more pronounced
      as the disorder level decreases. The region of anomalous behavior is bounded at
      low temperatures by two first-order phase transitions. The implications of the
      results are discussed.

PMID- 15169252
TI  - Quantum shuttle phenomena in a nanoelectromechanical single-electron transistor.
AB  - An analytical analysis of quantum shuttle phenomena in a nanoelectromechanical
      single-electron transistor has been performed in the realistic case, when the
      electron tunneling length is much greater than the amplitude of the zero point
      oscillations of the central island. It is shown that when the dissipation is
      below a certain threshold value, the vibrational ground state of the central
      island is unstable. The steady state into which this instability develops is
      studied. It is found that if the electric field E between the leads is much
      greater than a characteristic value E(q), the quasiclassical shuttle picture is
      recovered, while if E<<E(q) a new quantum regime of shuttle vibrations occurs. We
      show that in the latter regime small quantum fluctuations result in large (i.e.,
      finite in the limit variant Planck's over 2pi -->0) shuttle vibrations.

PMID- 15169253
TI  - Evidence for a quantum phase transition in Pr2-xCe(x)CuO4-delta from transport
      measurements.
AB  - The doping and temperature dependences of the Hall coefficient, R(H), and ab
      plane resistivity in the normal state down to 350 mK is reported for oriented
      films of the electron-doped high-T(c) superconductor Pr(2-x)Ce(x)CuO(4-delta).
      The doping dependences of beta (rho=rho(0)+ATbeta) and R(H) (at 350 mK) suggest a
      quantum phase transition at a critical doping near x=0.165.

PMID- 15169254
TI  - Orbital ordering in charge transfer insulators.
AB  - We discuss a new mechanism of orbital ordering, which in charge transfer
      insulators is more important than the usual exchange interactions and which can
      make the very type of the ground state of a charge transfer insulator, i.e., its
      orbital and magnetic ordering, different from that of a Mott-Hubbard insulator.
      This purely electronic mechanism allows us to explain why orbitals in Jahn-Teller
      materials typically order at higher temperatures than spins, and to understand
      the type of orbital ordering in a number of materials, e.g., K2CuF4, without
      invoking the electron-lattice interaction.

PMID- 15169255
TI  - Planar spin fluctuations with a quadratic thermal dependence rate in spin liquid
      Gd3Ga5O12.
AB  - The spin liquid properties of Gd3Ga5O12 have been examined using 155Gd Mossbauer
      spectroscopy down to 0.027 K. Information has been obtained concerning both the
      directional properties of the short range correlated moments and the thermal
      dependence of their spin fluctuation rates. Each Gd3+ spin (S=7/2) is found to be
      confined to a plane and its fluctuation rate decreases from approximately 2.8 x
      10(9) s(-1) at 0.4 K to approximately 0.03 x 10(9) s(-1) at 0.09 K following a
      close-to-quadratic thermal dependence.

PMID- 15169256
TI  - Spin anisotropy and slow dynamics in spin glasses.
AB  - We report on an extensive study of the influence of spin anisotropy on spin glass
      aging dynamics. New temperature cycle experiments allow us to compare
      quantitatively the memory effect in four Heisenberg spin glasses with various
      degrees of random anisotropy and one Ising spin glass. The sharpness of the
      memory effect appears to decrease continuously with the spin anisotropy. Besides,
      the spin glass coherence length is determined by magnetic field change
      experiments for the first time in the Ising sample. For three representative
      samples, from Heisenberg to Ising spin glasses, we can consistently account for
      both sets of experiments (temperature cycle and magnetic field change) using a
      single expression for the growth of the coherence length with time.

PMID- 15169257
TI  - Effective reduction of critical current for current-induced magnetization
      switching by a Ru layer insertion in an exchange-biased spin valve.
AB  - Recently, it has been predicted that a spin-polarized electrical current
      perpendicular to plane directly flowing through a magnetic element can induce
      magnetization switching through spin-momentum transfer. In this Letter, the first
      observation of current-induced magnetization switching (CIMS) in exchange-biased
      spin valves (ESPVs) at room temperature is reported. The ESPVs show the CIMS
      behavior under a sweeping dc current with a very high critical current density.
      It is demonstrated that a thin ruthenium (Ru) layer inserted between a free layer
      and a top electrode effectively reduces the critical current densities for the
      CIMS. An "inverse" CIMS behavior is also observed when the thickness of the free
      layer increases.

PMID- 15169258
TI  - Structure of ferromagnetic CrAs epilayers grown on GaAs(001).
AB  - Magnetic and structural properties of CrAs epilayers grown on GaAs(001) by
      molecular beam epitaxy have been studied. CrAs epilayers are orthorhombic for all
      thicknesses investigated but show a structural transition from a metastable phase
      for very thin films, to the usual bulk MnP-type orthorhombic phase at higher
      thicknesses. At intermediate thicknesses, there is a predominance of the new
      phase, although a contribution from the usual CrAs bulk phase remains clearly
      present. These results strongly suggest that the ferromagnetic signal measured at
      room temperature comes from the new metastable orthorhombic structure with an
      expanded b-axis induced by the substrate strain.

PMID- 15169259
TI  - Percolative conduction in the half-metallic-ferromagnetic and ferroelectric
      mixture of (La, Lu, Sr)MnO3.
AB  - The immiscibility between rhombohedral La(5/8)Sr(3/8)MnO3 and hexagonal LuMnO3
      leads to a microm-scale heterogeneous mixture of half-metallic-ferromagnetic and
      insulating-ferroelectric phases. Electronic conduction of the mixture exhibits
      nearly ideal percolation behavior in the paramagnetic state with a threshold of
      0.224(5) metal volume fraction and a resistivity scaling exponent t=2.1+/-0.1,
      consistent with the predicted universal behavior of classical percolation.
      However, far below T(C), t increases to 2.4+/-0.1, probably resulting from
      intergrain tunneling. Therefore, this system represents a unique example of the
      temperature-induced crossover from universal to nonuniversal behavior of t.

PMID- 15169260
TI  - Proposal for energy-time entanglement of quasiparticles in a solid-state device.
AB  - We present a proposal for the experimental observation of energy-time
      entanglement of quasiparticles in mesoscopic physics. This type of entanglement
      arises whenever correlated particles are produced at the same time and this time
      is uncertain in the sense of quantum uncertainty, as has been largely used in
      photonics. We discuss its feasibility for electron-hole pairs. In particular, we
      argue that junctions between materials in which electrons and holes,
      respectively, propagate ballistically and behave as "entanglers" for energy-time
      entanglement when irradiated with a continuous laser.

PMID- 15169261
TI  - Concurrence of mixed bipartite quantum states in arbitrary dimensions.
AB  - We derive a lower bound for the concurrence of mixed bipartite quantum states,
      valid in arbitrary dimensions. As a corollary, a weaker, purely algebraic
      estimate is found, which detects mixed entangled states with a positive partial
      transpose.

PMID- 15169262
TI  - Triggered qutrits for quantum communication protocols.
AB  - A general protocol in quantum information and communication relies in the ability
      of producing, transmitting, and reconstructing, in general, qunits. In this
      Letter we show for the first time the experimental implementation of these three
      basic steps on a pure state in a three-dimensional space, by means of the orbital
      angular momentum of the photons. The reconstruction of the qutrit is performed
      with tomographic techniques and a maximum-likelihood estimation method. For the
      tomographic reconstruction we used more than 2400 different projections. In this
      way we also demonstrate that we can perform any transformation in the three
      dimensional space.

PMID- 15169263
TI  - Internal states of active inclusions and the dynamics of an active membrane.
AB  - A theoretical model of a two-component fluid membrane containing lipids and two
      state active inclusions is presented. This model predicts several nonequilibrium
      morphology transitions. (i) Active pumping of the inclusions can drive a long
      wavelength undulation instability. (ii) Active excitation of the inclusions can
      induce aggregation of high-curvature excited inclusions. (iii) Active inclusion
      conformation changes can produce finite-size domains. The resulting steady state
      domain size depends on inclusion activities. For a stable membrane the height
      fluctuation spectrum in the long-wavelength limit is similar to previous studies
      which neglected the inclusion internal states.

PMID- 15169264
TI  - Phyllotactic patterns on plants.
AB  - We demonstrate how phyllotaxis (the arrangement of leaves on plants) and the
      deformation configurations seen on plant surfaces may be understood as the energy
      minimizing buckling pattern of a compressed shell (the plant's tunica) on an
      elastic foundation. The key new idea is that the strain energy is minimized by
      configurations consisting of special triads of almost periodic deformations. We
      reproduce a wide spectrum of plant patterns, all with the divergence angles
      observed in nature, and show how the occurrences of Fibonacci-like sequences and
      the golden angle are natural consequences.

PMID- 15169265
TI  - Site-specific dissociation of DNA bases by slow electrons at early stages of
      irradiation.
AB  - At the very early time of irradiation, ballistic secondary electrons are produced
      as the most abundant of the radiolytic species directly within DNA or its
      environment. Here, we demonstrate the propensity of such low-energy (<3 eV)
      electrons to damage DNA bases via an effective loss of hydrogen located at the
      specific nitrogen positions. Since this site is directly implicated in the
      bonding of nucleobases within DNA and since dehydrogenation of the nucleic acid
      bases has been observed to be the predominant dissociative channel, the present
      findings foreshadow significant implications for the initial molecular processes
      leading to genotoxicity in living cells following unwanted or intended exposure
      to ionizing radiation (e.g., sunbathing, air travel, radiotherapy, etc.).

PMID- 15169266
TI  - Formation of C60(2-) dianions in collisions between C60- and Na atoms.
AB  - We have observed the formation of C2-60 and C2-70 in collisions between C(
      )(60)/C(-)(70) and Na atoms. Cross sections for the electron transfer to the
      monoanion are determined to be 36+/-9 and 57+/-14 A(2) for C-60 and C-70,
      respectively. A simple model investigation suggests that the electron is
      transferred from a Na atom to a low-lying electronic state of the fullerene to
      form a dianion. The method leads to pico-ampere energetic beams of C60 dianions
      that can be used for spectroscopy and lifetime studies.

PMID- 15169267
TI  - Intermittent self-organization of scroll wave turbulence in three-dimensional
      excitable media.
AB  - We study the asymptotic behavior of scroll wave turbulence in large three
      dimensional excitable media modeled by FitzHugh-Nagumo equations. The focus is on
      the type of turbulence caused by negative tension of scroll wave filaments, which
      is considered to be one of the mechanisms of cardiac fibrillation. We discovered
      that the initial increase in turbulence complexity can be followed by
      intermittent self-organization, when complex filament tangles are replaced by a
      small number of relatively stable triple filament strands. The intermittency is
      the result of a competition between the destabilizing effect of negative tension
      and mutual attraction of filaments with similar orientation.

PMID- 15169268
TI  - Intermittency and clustering in a system of self-driven particles.
AB  - Intermittent behavior is shown to appear in a system of self-driven interacting
      particles. In the ordered phase, most particles move in the same approximate
      direction, but the system displays a series of intermittent bursts during which
      the order is temporarily lost. This intermittency is characterized and its
      statistical properties are found analytically for a reduced system containing
      only two particles. For large systems, the particles aggregate into clusters that
      play an essential role in the intermittent dynamics. The study of the cluster
      statistics shows that both the cluster sizes and the transition probability
      between them follow power-law distributions. The exchange of particles between
      clusters is shown to satisfy detailed balance.

PMID- 15169269
TI  - Distillation of bose-einstein condensates in a double-well potential.
AB  - Bose-Einstein condensates of sodium atoms, prepared in an optical dipole trap,
      were distilled into a second empty dipole trap adjacent to the first one. The
      distillation was driven by thermal atoms spilling over the potential barrier
      separating the two wells and then forming a new condensate. This process serves
      as a model system for metastability in condensates, provides a test for quantum
      kinetic theories of condensate formation, and also represents a novel technique
      for creating or replenishing condensates in new locations.

PMID- 15169270
TI  - Evidence for superfluidity in a resonantly interacting Fermi gas.
AB  - We observe collective oscillations of a trapped, degenerate Fermi gas of 6Li
      atoms at a magnetic field just above a Feshbach resonance, where the two-body
      physics does not support a bound state. The gas exhibits a radial breathing mode
      at a frequency of 2837(05) Hz, in excellent agreement with the frequency of nu(H)
      identical with sqrt[10nu(x)nu(y)/3]=2830(20) Hz predicted for a hydrodynamic
      Fermi gas with unitarity-limited interactions. The measured damping times and
      frequencies are inconsistent with predictions for both the collisionless mean
      field regime and for collisional hydrodynamics. These observations provide the
      first evidence for superfluid hydrodynamics in a resonantly interacting Fermi
      gas.

PMID- 15169271
TI  - Semiclassical time evolution of the reduced density matrix and dynamically
      assisted generation of entanglement for bipartite quantum systems.
AB  - Two particles, initially in a product state, become entangled when they come
      together and start to interact. Using semiclassical methods, we calculate the
      time evolution of the corresponding reduced density matrix rho(1), obtained by
      integrating out the degrees of freedom of one of the particles. We find that
      entanglement generation sensitively depends (i) on the interaction potential,
      especially on its strength and range, and (ii) on the nature of the underlying
      classical dynamics. Under general statistical assumptions, and for short-ranged
      interaction potentials, we find that P(t) decays exponentially fast in a chaotic
      environment, whereas it decays only algebraically in a regular system. In the
      chaotic case, the decay rate is given by the golden rule spreading of one
      particle states due to the two-particle coupling, but cannot exceed the system's
      Lyapunov exponent.

PMID- 15169272
TI  - Achieving a BCS transition in an atomic Fermi gas.
AB  - We consider a gas of cold fermionic atoms having two spin components with
      interactions characterized by their s-wave scattering length a. At positive
      scattering length the atoms form weakly bound bosonic molecules which can be
      evaporatively cooled to undergo Bose-Einstein condensation, whereas at negative
      scattering length BCS pairing can take place. It is shown that, by adiabatically
      tuning the scattering length a from positive to negative values, one may
      transform the molecular Bose-Einstein condensate into a highly degenerate atomic
      Fermi gas, with the ratio of temperature to Fermi temperature T/T(F)
      approximately 10(-2). The corresponding critical final value of k(F)/a/, which
      leads to the BCS transition, is found to be about one-half, where k(F) is the
      Fermi momentum.

PMID- 15169273
TI  - Detection of spatial correlations in an ultracold gas of fermions.
AB  - Spatial correlations are observed in an ultracold gas of fermionic atoms close to
      a Feshbach resonance. The correlations are detected by inducing spin-changing rf
      transitions between pairs of atoms. We observe the process in the strongly
      interacting regime for attractive as well as for repulsive atom-atom interactions
      and both in the regime of high and low quantum degeneracy. The observations are
      compared with a two-particle model that provides theoretical predictions for the
      measured rf transition rates.

PMID- 15169275
TI  - Rules for transition rates in nonequilibrium steady states.
AB  - Just as transition rates in a canonical ensemble must respect the principle of
      detailed balance, constraints exist on transition rates in driven steady states.
      I derive those constraints, by maximum information-entropy inference, and apply
      them to the steady states of driven diffusion and a sheared lattice fluid. The
      resulting ensemble can potentially explain nonequilibrium phase behavior and, for
      steady shear, gives rise to stress-mediated long-range interactions.

PMID- 15169274
TI  - Berry phase in a composite system.
AB  - The Berry phase in a composite system with one driven subsystem has been studied
      in this Letter. We choose two coupled spin-1 / 2 systems as the composite system;
      one of the subsystems is driven by a time-dependent magnetic field. We show how
      the Berry phases depend on the coupling between the two subsystems, and the
      relation between the Berry phases of the composite system and those of its
      subsystems.

PMID- 15169277
TI  - Neutron stars as type-I superconductors.
AB  - In a recent paper by Link, it was pointed out that the standard picture of the
      neutron star core composed of a mixture of a neutron superfluid and a proton type
      II superconductor is inconsistent with observations of a long period precession
      in isolated pulsars. In the following we will show that an appropriate treatment
      of the interacting two-component superfluid (made of neutron and proton Cooper
      pairs), when the structure of proton vortices is strongly modified, may
      dramatically change the standard picture, resulting in a type-I superconductor.
      In this case the magnetic field is expelled from the superconducting regions of
      the neutron star, leading to the formation of the intermediate state when
      alternating domains of superconducting matter and normal matter coexist.

PMID- 15169278
TI  - What does a strongly excited 't Hooft-Polyakov magnetic monopole do?
AB  - The time evolution of strongly excited SU(2) Bogomol'nyi-Prasad-Sommerfield
      magnetic monopoles in Minkowski spacetime is investigated by using numerical
      simulations based on the technique of conformal compactification and on the use
      of the hyperboloidal initial value problem. It is found that an initially static
      monopole does not radiate the entire energy of the exciting pulse toward future
      null infinity. Rather, a long-lasting quasistable "breathing state" develops in
      the central region and certain expanding shell structures-built up by very high
      frequency oscillations-are formed in the far away region.

PMID- 15169279
TI  - Resonant excitations of the 't Hooft-Polyakov monopole.
AB  - The spherically symmetric magnetic monopole in an SU(2) gauge theory coupled to a
      massless Higgs field is shown to possess an infinite number of resonances or
      quasinormal modes. These modes are eigenfunctions of the isospin 1 perturbation
      equations with complex eigenvalues, E(n)=omega(n)-igamma(n), satisfying the
      outgoing radiation condition. For n--> infinity, their frequencies omega(n)
      approach the mass of the vector boson, M(W), while their lifetimes 1/gamma(n)
      tend to infinity. The response of the monopole to an arbitrary initial
      perturbation is largely determined by these resonant modes, whose collective
      effect leads to the formation of a long living breatherlike excitation with an
      amplitude decaying at late times as t(-5/6).

PMID- 15169276
TI  - Measurement of the flux of ultrahigh energy cosmic rays from monocular
      observations by the High Resolution Fly's Eye experiment.
AB  - We have measured the cosmic ray spectrum above 10(17.2) eV using the two air
      fluorescence detectors of the High Resolution Fly's Eye observatory operating in
      monocular mode. We describe the detector, phototube, and atmospheric
      calibrations, as well as the analysis techniques for the two detectors. We fit
      the spectrum to a model consisting of galactic and extragalactic sources.

PMID- 15169280
TI  - Production and state-selective detection of ultracold RbCs molecules.
AB  - Using resonance-enhanced two-photon ionization, we detect ultracold, metastable
      RbCs molecules formed in their lowest triplet state a (3)Sigma(+) via
      photoassociation in a laser-cooled mixture of 85Rb and 133Cs atoms. We obtain
      extensive bound-bound excitation spectra of these molecules, which provide
      detailed information about their vibrational distribution, as well as
      spectroscopic data on several RbCs molecular states including a (3)Sigma(+), (2)
      (3)Sigma(+), and (1) (1)Pi. Analysis of this data allows us to predict strong
      transitions from observed levels to the absolute vibronic ground state of RbCs,
      potentially allowing the production of stable, ultracold polar molecules at rates
      in excess of 10(6) s(-1).

PMID- 15169281
TI  - Counting individual 41Ca atoms with a magneto-optical trap.
AB  - Atom trap trace analysis, a novel method based upon laser trapping and cooling,
      is used to count individual atoms of 41Ca present in biomedical samples with
      isotopic abundance levels between 10(-8) and 10(-10). The method is calibrated
      against resonance ionization mass spectrometry, demonstrating good agreement
      between the two methods. The present system has a counting efficiency of 2x10(
      7). Within 1 h of observation time, its 3-sigma detection limit on the isotopic
      abundance of 41Ca reaches 4.5x10(-10).

PMID- 15169282
TI  - Beyond the T1 limit: singlet nuclear spin states in low magnetic fields.
AB  - Low-field nuclear spin singlet states may be used to store nuclear spin order in
      a room temperature liquid for a time much longer than the spin-lattice relaxation
      time constant T1. The low-field nuclear spin singlets are unaffected by
      intramolecular dipole-dipole relaxation, which is generally the predominant
      relaxation mechanism. We demonstrate storage of nuclear spin order for more than
      10 times longer than the measured value of T1. This phenomenon may facilitate the
      development of nuclear spin hyperpolarization methods and may allow the study of
      motional processes which occur too slowly for existing NMR techniques. This is
      the first time that the memory of nuclear spins has been extended well beyond the
      T1 limit in a system lacking intrinsic magnetic equivalence.

PMID- 15169284
TI  - Spin-orbit coupling and Berry phase with ultracold atoms in 2D optical lattices.
AB  - We show how spin-orbit coupling and Berry phase can appear in two-dimensional
      optical lattices by coupling atoms' internal degrees of freedom to radiation. The
      Rashba Hamiltonian, a standard description of spin-orbit coupling for two
      dimensional electrons, is obtained for the atoms under certain circumstances. We
      discuss the possibility of observing associated phenomena, such as the anomalous
      Hall and spin Hall effects, with cold atoms in optical lattices.

PMID- 15169283
TI  - Lifetime measurement of the 3P2 metastable state of strontium atoms.
AB  - We have measured the lifetime of the 5s5p 3P2 metastable state of strontium atoms
      by magneto-optically trapping the decayed atoms to the ground state, which
      allowed sensitive detection of the rare decay events. We found that the blackbody
      radiation-induced decay was the dominant decay channel for the state at T=300 K.
      The lifetime was determined to be 520(+310)(-140) s in the limit of zero
      temperature, arguably the longest lifetime ever determined in a laboratory
      environment.

PMID- 15169285
TI  - Interference effect in electron emission in heavy ion collisions with h2 detected
      by comparison with the measured electron spectrum from atomic hydrogen.
AB  - Direct evidence of the interference effect in the electron emission spectra from
      ionization of molecular hydrogen in collisions with bare C and F ions at
      relatively low collision energies is presented. Oscillations due to the
      interference are deduced by comparing the measured double differential cross
      sections of the electrons emitted from molecular hydrogen to those emitted from
      atomic hydrogen, rather than using the calculated cross sections for H as in a
      previous report. We believe these experimental data provide stronger support for
      the evidence of the interference effect. We show that it is not only a feature of
      very high energy collisions, but also a feature to be observed in relatively
      lower energy collisions.

PMID- 15169286
TI  - Non-Gaussian statistics from individual pulses of squeezed light.
AB  - We describe the observation of a "degaussification" protocol that maps individual
      pulses of squeezed light onto non-Gaussian states. This effect is obtained by
      sending a small fraction of the squeezed vacuum beam onto an avalanche
      photodiode, and by conditioning the single-shot homodyne detection of the
      remaining state upon the photon-counting events. The experimental data provide
      clear evidence of phase-dependent non-Gaussian statistics. This protocol is
      closely related to the first step of an entanglement distillation procedure for
      continuous variables.

PMID- 15169287
TI  - Distinguishing genuine entangled two-photon-polarization sfrom independently
      generated pairs of entangled photons.
AB  - A scheme to distinguish entangled two-photon-polarization (ETP) states from two
      independent entangled one-photon-polarization (EOP) states is proposed. Using
      this scheme, the experimental generation of ETP by parametric down-conversion is
      confirmed through the anticorrelations among three orthogonal two-photon
      polarization states. The estimated fraction of ETP among the correlated photon
      pairs is 37% in the present experimental setup.

PMID- 15169288
TI  - Experimental synchronization of spatiotemporal disorder.
AB  - We report experimental evidence of a time-lag synchronization of spatiotemporal
      complexity. The experiments were performed on two unidirectionally coupled,
      nonlinear-optical systems of single-feedback type. Synchronization was
      investigated for different degrees of complexity of the spontaneous structures,
      which were analyzed with cross-correlation functions and mutual information.
      Numerical simulations yield comparable results and throw a light on the impeding
      role of spatial inhomogeneities.

PMID- 15169289
TI  - Noisy inflows cause a shedding-mode switching in flow past an oscillating
      cylinder.
AB  - Vortex streets formed behind oscillating bluff bodies consist of arrays of groups
      of two, three, or four vortices classified as 2S, P+S, and 2P shedding modes,
      respectively. The prevailing dominant mode depends primarily on the amplitude and
      the frequency of the oscillation and on the Reynolds number. We investigate the
      effect of noise at the inflow on the stability of these vortex modes in laminar
      flow past a circular cylinder. We employ stochastic simulations based on a new
      polynomial chaos method to study the shedding-mode switching from a P+S pattern
      to a 2S mode in the presence of noise.

PMID- 15169290
TI  - Different modes of a capacitively coupled radio-frequency discharge in methane.
AB  - The transition between different regimes of a capacitevely coupled radio
      frequency gas discharge in methane is studied with a combined particle-in-cell
      Monte Carlo collision algorithm over a wide range of gas pressure P and discharge
      current j. The results of this study are compared with known experimental and
      numerical results and summarized on a P-j phase diagram, which constitutes the
      areas of existence of different discharge regimes.

PMID- 15169291
TI  - Paul trap simulator experiment to model intense-beam propagation in alternating
      gradient transport systems.
AB  - The results presented here demonstrate that the Paul trap simulator experiment
      (PTSX) simulates the propagation of intense charged particle beams over distances
      of many kilometers through magnetic alternating-gradient (AG) transport systems
      by making use of the similarity between the transverse dynamics of particles in
      the two systems. Plasmas have been trapped that correspond to normalized
      intensity parameters s=omega(2)(p)(0)/2omega(2)(q)<or=0.8, where omega(p)(r) is
      the plasma frequency and omega(q) is the average transverse focusing frequency in
      the smooth-focusing approximation. The measured rms radius of the beam is
      consistent with a model, equally applicable to both PTSX and AG systems. The PTSX
      device confines one-component cesium ion plasmas for hundreds of milliseconds,
      which is equivalent to over 10 km of beam propagation.

PMID- 15169292
TI  - Coulomb crystallization in expanding laser-cooled neutral plasmas.
AB  - We present long-time simulations of expanding ultracold neutral plasmas,
      including a full treatment of the strongly coupled ion dynamics. Thereby, the
      relaxation of the expanding laser-cooled plasma is studied, taking into account
      elastic as well as inelastic collisions. It is demonstrated that, depending on
      the initial conditions, the ionic component of the plasma may exhibit short-range
      order or even a superimposed long-range order resulting in concentric ion shells.
      In contrast to ionic plasmas confined in traps, the shell structures build up
      from the center of the plasma cloud rather than from the periphery.

PMID- 15169293
TI  - Reversible, surface-controlled structure transformation in nanoparticles induced
      by an aggregation state.
AB  - The structure of 3 nm ZnS nanoparticles differs from that of bulk ZnS and is
      shown to vary with the particle aggregation state. Dispersed or weakly aggregated
      nanoparticles in suspension have a more distorted internal structure than
      strongly aggregated nanoparticles. Reversible switching between distorted and
      crystalline structures can be induced by changing the aggregation state via slow
      drying and ultrasonic agitation. The transformation was analyzed using pair
      distribution function data from wide angle x-ray diffraction and the aggregation
      state monitored via small angle x-ray scattering. Molecular modeling provides
      insight into particle-particle interactions that induce the structural changes.
      The reversible nature also implies a low activation energy of nanoparticle
      transformation and indicates that distorted nanoparticles are not trapped in a
      metastable state.

PMID- 15169294
TI  - Formation of thermal vacancies on the Si sublattice of the intermetallic compound
      MoSi2.
AB  - For a detailed understanding of high-temperature processes in complex solids the
      identification of the sublattice on which thermal defects are formed is of basic
      interest. Theoretical studies in intermetallic compounds favor a particular
      sublattice for thermal vacancy formation. In the present study we detect in
      ordered MoSi2 thermal vacancies with a low formation enthalpy of H(F)(V)=(1.6+/
      0.1) eV, and we succeed in showing by experimental and theoretical efforts that
      they are preferentially formed on the Si sublattice. By these data self-diffusion
      in MoSi2 can be understood.

PMID- 15169295
TI  - Effect of monomer geometry on the fractal structure of colloidal rod aggregates.
AB  - The fractal structure of clusters formed by diffusion-limited aggregation of
      rodlike particles is characterized over three decades of the scattering vector q,
      and displays an unexpected dependence on the aspect ratio of the constituent
      monomers. Monte Carlo simulations of aggregating Brownian rods corroborate the
      experimental finding that the measured fractal dimension is an increasing
      function of the monomer aspect ratio. Moreover, increasing the rod aspect ratio
      eliminates the structural distinction between diffusion- and reaction-limited
      cluster aggregation that is observed for spheres.

PMID- 15169296
TI  - Doping by large-size-mismatched impurities: the microscopic origin of arsenic- or
      antimony-doped p-type zinc oxide.
AB  - Based on first-principles calculations, a model for large-size-mismatched group-V
      dopants in ZnO is proposed. The dopants do not occupy the O sites as is widely
      perceived, but rather the Zn sites: each forms a complex with two spontaneously
      induced Zn vacancies in a process that involves fivefold As coordination.
      Moreover, an As(Zn)-2V(Zn) complex may have lower formation energy than any of
      the parent defects. Our model agrees with the recent observations that both As
      and Sb have low acceptor-ionization energies and that to obtain p-type ZnO
      requires O-rich growth or annealing conditions.

PMID- 15169297
TI  - Investigation of transition States in bulk and freestanding film polymer glasses.
AB  - We have performed transition state searches on the potential energy landscape for
      bulk and freestanding film polymer glasses and identified connected minima. An
      analysis of the displacements between minima shows that the sites that undergo
      the greatest displacement are highly localized in space for both the bulk and the
      thin-film systems studied. In the case of the thin film, the clusters originate
      at the surface and penetrate into the center of the film thereby coupling the
      relaxation in the center of the film to the mobile surface layer. Furthermore,
      the energy barriers between minima are lower in the thin film than in the bulk
      system. These findings can rationalize the experimentally observed depression of
      the glass transition temperature in freestanding polymer films.

PMID- 15169298
TI  - Pressure-induced sharp coordination change in liquid germanate.
AB  - Local structures around germanium in liquid germanate have been investigated by
      means of in situ x-ray absorption measurements up to 9 GPa at 1273 K. Liquid
      germanate consisting of tetrahedrally coordinated germanium contracts with
      increasing pressure without significant changes in the local structure up to 2.5
      GPa and then shows an abrupt fourfold-to-sixfold coordination change around 3
      GPa. The coordination change is completed below 4 GPa where upon a high-density
      liquid consisting of octahedrally coordinated germanium becomes stable. The GeO6
      octahedron in the high-density liquid is more compressible than that in solids.

PMID- 15169299
TI  - Activation energies for quantum diffusion of hydrogen in metals and on metal
      surfaces using delocalized nuclei within the density-functional theory.
AB  - Hydrogen diffusion on the Cu(001) surface and in bulk Nb and Ta is studied in the
      quantum regime using first-principles electronic-structure calculations. We
      present, for the first time, a direct density-functional calculation of the
      activation energy required to establish the quantum-mechanically delocalized
      hydrogen coincidence configuration and of the corresponding tunneling matrix
      element. For the two bulk systems a direct comparison can be made with nuclear
      magnetic resonance data, and we find excellent agreement for both the coincidence
      energy and the tunneling matrix element.

PMID- 15169300
TI  - Probing adsorbate state lifetime with low energy ions.
AB  - Charge transfer during back scattering of a H- ion from a Cu(111) metal surface
      with Cs adsorbates is studied theoretically within a wave packet propagation
      approach. We show that the long lifetime of the Cs-localized state in the
      Cs/Cu(111) system deeply modifies the nature of projectile-surface charge
      transfer, suppressing its irreversible character. Back and forth electron
      transfer between the projectile and the adsorbate during the collision results in
      characteristic oscillations in the H- yield as a function of projectile energy.

PMID- 15169301
TI  - Molecular forces caused by the confinement of thermal noise.
AB  - We have investigated spontaneous surface instabilities of very thin polymer
      films. Film stability and the wavelength of the dominating unstable mode were
      found to depend sensitively on the media adjacent to the film. Our experimental
      results cannot be explained by van der Waals interactions alone. To account for
      the presence of an additional destabilizing force, we propose that the
      geometrical confinement of thermally excited acoustic waves gives rise to a force
      that is strong enough to destabilize thin films. This thermoacoustic effect is of
      similar magnitude as van der Waals forces.

PMID- 15169302
TI  - Direct measurement of the g factor of composite fermions.
AB  - The activation gap Delta of the fractional quantum Hall states at constant
      fillings nu=2/3 and 2/5 has been measured as a function of the perpendicular
      magnetic field B. A linear dependence of Delta on B is observed while approaching
      the spin-polarization transition. This feature allows a direct measurement of the
      g factor of composite fermions which appears to be heavily renormalized by
      interactions and strongly sensitive to the electronic filling factor.

PMID- 15169303
TI  - Controlled dephasing of a quantum dot in the Kondo regime.
AB  - Kondo correlation in a spin polarized quantum dot (QD) results from the dynamical
      formation of a spin singlet between the dot's net spin and a Kondo cloud of
      electrons in the leads, leading to enhanced coherent transport through the QD. We
      demonstrate here significant dephasing of such transport by coupling the QD and
      its leads to potential fluctuations in a nearby "potential detector." The
      qualitative dephasing is similar to that of a QD in the Coulomb blockade regime
      in spite of the fact that the mechanism of transport is quite different. A much
      stronger than expected suppression of coherent transport is measured, suggesting
      that dephasing is induced mostly in the "Kondo cloud" of electrons within the
      leads and not in the QD.

PMID- 15169304
TI  - Oscillatory magnetothermopower and resonant phonon drag in a high-mobility 2D
      electron gas.
AB  - Experimental and theoretical evidence is presented for new low-magnetic-field
      (B<5 kG) 1/B oscillations in the thermoelectric power of a high-mobility
      GaAs/AlGaAs two-dimensional (2D) electron gas. The oscillations result from inter
      Landau-level resonances of acoustic phonons carrying a momentum equal to twice
      the Fermi wave number at B=0. Numerical calculations show that both 3D and 2D
      phonons can contribute to this effect.

PMID- 15169305
TI  - Diffusive diffraction of the local ESR pulse-gradient spin-echo signal in a
      restricted one-dimensional conductor.
AB  - The diffusive motion of the conducting electrons in the one-dimensional organic
      conductor FA2PF6 (FA, Fluoranthene) is studied with the ESR pulse-gradient spin
      echo (PGSE) signal combined with spatial density ESR imaging. A local measurement
      of the short restricted regions reveals diffraction patterns in the local PGSE
      data. A model calculation adapted to the local measurements provides a highly
      accurate quantitative description of the results. The appearance of these
      patterns provides information about the diffusive motion of the charge at the
      crystal boundaries.

PMID- 15169306
TI  - Where is the shot noise of a quantum point contact?
AB  - Reznikov et al. [Phys. Rev. Lett. 75, 3340 (1995)]] have presented definitive
      observations of nonequilibrium noise in a quantum point contact. Especially
      puzzling is the "anomalous" peak structure of the excess noise measured at
      constant current; to date it remains unexplained. We show that their experiment
      directly reveals the deep link between conservation principles in the electron
      gas and its low-dimensional, mesoscopic behavior. The keys to that connection are
      gauge invariance and the compressibility sum rule. These are central not only to
      the experiment of Reznikov et al., but to the very nature of all mesoscopic
      transport.

PMID- 15169307
TI  - Vortex state in double transition superconductors.
AB  - The novel vortex phase and nature of the double transition field are investigated
      by two-component Ginzburg-Landau theory in a situation where fourfold-twofold
      symmetric superconducting double transition occurs. The deformation from 60
      degrees triangular vortex lattice and a possibility of the vortex sheet structure
      are discussed. In the presence of the gradient coupling, the transition changes
      to a crossover at finite field. These characters are important to identify the
      multiple superconducting phase in PrOs4Sb12.

PMID- 15169308
TI  - Do vortices entangle?
AB  - We propose an experiment for directly constructing and locally probing
      topologically entangled states of superconducting vortices which can be performed
      with present-day technology. Calculations using an elastic string vortex model
      indicate that as the pitch (the winding angle divided by the vertical distance)
      increases, the vortices approach each other. At values of the pitch higher than a
      maximum value the entangled state becomes unstable to collapse via a singularity
      of the model. We provide predicted experimental signatures for both vortex
      entanglement and vortex cutting. The local probe we propose can also be used to
      explore a wide range of other quantities.

PMID- 15169309
TI  - Resonating valence bond wave function for the two-dimensional fractional spin
      liquid.
AB  - The unconventional low-lying spin excitations, recently observed in neutron
      scattering experiments on Cs2CuCl4, are explained with a spin liquid wave
      function. The dispersion relation as well as the wave vector of the
      incommensurate spin correlations are well reproduced within a projected BCS wave
      function with gapless and fractionalized spin-1/2 excitations around the nodes of
      the BCS gap function. The proposed wave function is shown to be very accurate for
      one-dimensional spin-1/2 systems and remains similarly accurate in the two
      dimensional model corresponding to Cs2CuCl4, thus representing a good ansatz for
      describing spin fractionalization in two dimensions.

PMID- 15169310
TI  - Thermodynamic and transport measurements of superconducting Na0.3CoO2.1.3H2O
      single crystals prepared by electrochemical deintercalation.
AB  - Superconducting single crystal samples of Na0.3CoO2.1.3H(2)O have been produced
      using an electrochemical technique which dispenses with the usual bromine
      chemical deintercalation method. In fully hydrated crystals, susceptibility and
      specific heat measurements confirm that bulk superconductivity has been achieved.
      The extracted normal state density of states indicates Fermi-liquid behavior with
      strong mass enhancement and a modest Wilson ratio. Measurements of H(c2) for H
      parallel c and H parallel ab reveal significant anisotropy, and the extracted
      value for the coherence length is about 100 A, consistent with an extremely
      narrow bandwidth.

PMID- 15169311
TI  - Nodal order parameter in electron-doped Pr(2-x)CexCuO(4-delta) superconducting
      films.
AB  - The London penetration depth, lambda(ab)(T), is reported for thin films of the
      electron-doped superconductor Pr(2-x)Ce(x)CuO(4-delta) with varying Ce
      concentration, x=0.13, 0.15, and 0.17. Measurements down to 0.35 K were carried
      out using a tunnel-diode oscillator with excitation fields applied both
      perpendicular and parallel to the conducting planes. Films at all three doping
      levels exhibited power law behavior indicative of d-wave pairing with impurity
      scattering. These results are fully consistent with previous measurements on
      single crystals.

PMID- 15169312
TI  - Magnetic imaging of pearl vortices in artificially layered
      (Ba0.9Nd0.1CuO2+x)m/(CaCuO2)n systems.
AB  - We have used scanning SQUID magnetometry to image vortices in ultrathin
      (Ba0.9Nd0.1CuO2+x)(m)/(CaCuO2)(n) high temperature superconductor samples, with
      as few as three superconducting CuO2 planes. The Pearl lengths
      (Lambda=2lambda(2)(L)/d, lambda(L) the London penetration depth, d the
      superconducting film thickness) in these samples, as determined by fits to the
      vortex images, agree with those by local susceptibility measurements, and can be
      as long as 1 mm. The in-plane penetration depths lambda(ab) inferred from the
      Pearl lengths are longer than many bulk cuprates with comparable critical
      temperatures. We speculate on the causes of the long penetration depths, and on
      the possibility of exploiting the unique properties of these superconductors for
      basic experiments.

PMID- 15169313
TI  - Lack of ultrametricity in the low-temperature phase of three-dimensional Ising
      spin glasses.
AB  - We study the low-temperature spin-glass phases of the Sherrington-Kirkpatrick
      (SK) model and of the 3-dimensional short-range Ising spin-glass (3DISG). By
      using clustering to focus on the relevant parts of phase space and reduce finite
      size effects, we found that for the SK model ultrametricity becomes clearer as
      the system size increases, while for the short-range case our results indicate
      the opposite, i.e., lack of ultrametricity. Another method, which does not rely
      on clustering, indicates that the mean-field solution works for the SK model but
      does not apply in detail to the 3DISG, for which stochastic stability is also
      violated.

PMID- 15169314
TI  - Ising transition in the two-dimensional quantum J1-J2 Heisenberg model.
AB  - We study the thermodynamics of the spin-S two-dimensional quantum Heisenberg
      antiferromagnet on the square lattice with nearest (J1) and next-nearest (J2)
      neighbor couplings in its collinear phase (J(2)/J(1)>0.5), using the pure-quantum
      self-consistent harmonic approximation. Our results show the persistence of a
      finite-temperature Ising phase transition for every value of the spin, provided
      that the ratio J(2)/J(1) is greater than a critical value corresponding to the
      onset of collinear long-range order at zero temperature. We also calculate the
      spin and temperature dependence of the collinear susceptibility and correlation
      length, and we discuss our results in light of the experiments on Li2VOSiO4 and
      related compounds.

PMID- 15169315
TI  - Theory of insulator metal transition and colossal magnetoresistance in doped
      manganites.
AB  - The persistent proximity of insulating and metallic phases, a puzzling
      characteristic of manganites, is argued to arise from the self-organization of
      the twofold degenerate e(g) orbitals of Mn into localized Jahn-Teller (JT)
      polaronic levels and broad band states due to the large electron-JT phonon
      coupling present in them. We describe a new two band model with strong
      correlations and a dynamical mean-field theory calculation of equilibrium and
      transport properties. These explain the insulator metal transition and colossal
      magnetoresistance quantitatively, as well as other consequences of two state
      coexistence.

PMID- 15169316
TI  - Abrupt discontinuity of the bulk modulus pressure dependence in Fe64Ni36.
AB  - X-ray diffraction and ultrasonic measurements have been carried out
      simultaneously up to 7 GPa at ambient temperature on a polycrystalline sample of
      Fe64Ni36 Invar alloy. The bulk modulus is found to increase linearly with
      pressure with an unusual low value (1.4) of dB/dP up to about 3.1(2) GPa followed
      by a regular slope (3.6) at higher pressure. The observation of these two
      distinct regimes is in qualitative agreement with previous results on the
      variation of the iron magnetic moment, and can be interpreted using the 2gamma
      state model in terms of gradual population of low spin-small volume state at the
      expense of the high spin-large volume state under pressure.

PMID- 15169317
TI  - Optical Stark effect in a quantum dot: ultrafast control of single exciton
      polarizations.
AB  - We report the first experimental study of the optical Stark effect in single
      semiconductor quantum dots (QD). For below band gap excitation, two-color pump
      probe spectra show dispersive line shapes caused by a light-induced blueshift of
      the excitonic resonance. The line shape depends strongly on the excitation field
      strength and is determined by the pump-induced phase shift of the coherent QD
      polarization. Transient spectral oscillations can be understood as rotations of
      the QD polarization phase with negligible population change. Ultrafast control of
      the QD polarization is demonstrated.

PMID- 15169318
TI  - Anomalous power law dispersions in ac conductivity and permittivity shown to be
      characteristics of microstructural electrical networks.
AB  - The frequency dependent ac conductivity and permittivity of porous lead zirconate
      titanate ceramic with the pore volume filled with water are shown to match the
      simulated electrical response of a large network of randomly positioned resistors
      and capacitors. Anomalous power law dispersions in conductivity and permittivity
      are shown to be an electrical response characteristic of the microstructural
      network formed by the porous lead zirconate titanate pore structure. The
      anomalous power law dispersions of a wide range of materials are also suggested
      to be microstructural network characteristics.

PMID- 15169319
TI  - Cheat sensitive quantum bit commitment.
AB  - We define cheat sensitive cryptographic protocols between mistrustful parties as
      protocols which guarantee that, if either cheats, the other has some nonzero
      probability of detecting the cheating. We describe an unconditionally secure
      cheat sensitive nonrelativistic bit commitment protocol which uses quantum
      information to implement a task which is classically impossible; we also describe
      a simple relativistic protocol.

PMID- 15169320
TI  - Water induced effects on the thermal response of a protein.
AB  - A model protein and surrounding water have been investigated at different
      temperatures. We have detected an anomalous compression of the protein near the
      freezing point of water-a compression not obviously related to the negative
      thermal expansion of the solvent. Moreover, the physiological protein working
      temperature (T=300 K) appears to be related to the activation of exchange of
      vicinal water with the bulk and the concomitant absorption of heat by hydrophilic
      amino acids. The inferred activation was interpreted on the basis of degenerate
      tetrahedral order between the hydration shell and the bulk. The results support
      the notion that the dynamics of vicinal water makes a substantial contribution to
      the activity optimum of proteins.

PMID- 15169321
TI  - Topological origin of the phase transition in a model of DNA denaturation.
AB  - The hypothesis that phase transitions originate from some topological change of
      the critical level hypersurface of the potential energy receives direct evident
      support by our study of the Bishop-Peyrard model of DNA thermal denaturation.

PMID- 15169322
TI  - Coherent electron transport through an azobenzene molecule: a light-driven
      molecular switch.
AB  - We apply a first-principles computational approach to study a light-sensitive
      molecular switch. The molecule that comprises the switch can convert between a
      trans and a cis configuration upon photoexcitation. We find that the conductance
      of the two isomers varies dramatically, which suggests that this system has
      potential application as a molecular device. A detailed analysis of the band
      structure of the metal leads and the local density of states of the system
      reveals the mechanism of the switch.

PMID- 15169323
TI  - Comment on "Spontaneous-emission suppression on arbitrary atomic transitions".

PMID- 15169324
TI  - Comment on "Spontaneous-emission suppression on arbitrary atomic transitions".

PMID- 15169326
TI  - Comment on "Rotational drag on DNA: a single molecule experiment".

PMID- 15169328
TI  - Comment on "Global climate models violate scaling of the observed atmospheric
      variability".

PMID- 15169330
TI  - Correlations in atomic systems: diagnosing coherent superpositions.
AB  - While investigating quantum correlations in atomic systems, we note that single
      measurements contain information about these correlations. Using a simple model
      of measurement-analogous to the one used in quantum optics-we show how to extract
      higher-order correlation functions from individual "photographs" of the atomic
      sample. As a possible application, we apply the method to detect a subtle phase
      coherence in mesoscopic superpositions.

PMID- 15169331
TI  - Collective molecule formation in a degenerate Fermi gas via a Feshbach resonance.
AB  - We model collisionless collective conversion of a degenerate Fermi gas of atoms
      into bosonic molecules via a Feshbach resonance, treating the bosonic molecules
      as a classical field and seeding the pairing amplitudes with random phases. A
      dynamical instability of the Fermi sea against association with molecules drives
      the conversion. The model qualitatively reproduces several experimental
      observations [Regal et al., Nature (London), (2003)]. We predict that the initial
      temperature of the Fermi gas sets the limit for the efficiency of atom-molecule
      conversion.

PMID- 15169332
TI  - Dynamical control of macroscopic quantum tunneling.
AB  - We show that the quantum Zeno and anti-Zeno effects are realizable for
      macroscopic quantum tunneling by current-bias modulation in Josephson junctions
      (and their analogs in atomic condensates).

PMID- 15169333
TI  - Fixed points of quantum gravity.
AB  - Euclidean quantum gravity is studied with renormalization group methods.
      Analytical results for a nontrivial ultraviolet fixed point are found for
      arbitrary dimensions and gauge fixing parameters in the Einstein-Hilbert
      truncation. Implications for quantum gravity in four dimensions are discussed.

PMID- 15169334
TI  - Constraining the topology of the universe.
AB  - The first year data from the Wilkinson Microwave Anisotropy Probe are used to
      place stringent constraints on the topology of the Universe. We search for pairs
      of circles on the sky with similar temperature patterns along each circle. We
      restrict the search to back-to-back circle pairs, and to nearly back-to-back
      circle pairs, as this covers the majority of the topologies that one might hope
      to detect in a nearly flat universe. We do not find any matched circles with
      radius greater than 25 degrees. For a wide class of models, the nondetection
      rules out the possibility that we live in a universe with topology scale smaller
      than 24 Gpc.

PMID- 15169335
TI  - Possibility of observable amount of gravitational waves from inflation.
AB  - The curvaton and inhomogeneous reheating scenarios for the generation of the
      cosmological curvature perturbation on large scales represent an alternative to
      the standard slow-roll scenario. The basic assumption of these mechanisms is that
      the initial curvature perturbation due to the inflaton field is negligible. This
      is usually attained by lowering the energy scale of inflation, thereby concluding
      that the amount of gravitational waves produced during inflation is highly
      suppressed. We show that the curvaton and inhomogeneous reheating scenarios are
      compatible with a level of gravity-wave fluctuations which may well be observed
      in future satellite experiments.

PMID- 15169337
TI  - Regularization of the linearized gravitational self-force for branes.
AB  - We discuss the linearized, gravitational self-interaction of a brane of arbitrary
      codimension in a spacetime of arbitrary dimension. We find that in the
      codimension two case the gravitational self-force is exactly zero for a Nambu
      Goto equation of state, generalizing a previous result for a string in four
      dimensions. For the case of a 3-brane, this picks out the case of a six
      dimensional brane-world model as having special properties that we discuss. In
      particular, we see that bare tension on the brane has no effect locally,
      suppressing the cosmological constant problem.

PMID- 15169338
TI  - Spontaneous violation of CP symmetry in the strong interactions.
AB  - Some time ago Dashen [Phys. Rev. D 3, 1879 (1971)] pointed out that spontaneous
      CP violation can occur in the strong interactions. I show how a simple effective
      Lagrangian exposes the remarkably large domain of quark mass parameters for which
      this occurs. I close with some warnings for lattice simulations.

PMID- 15169336
TI  - Evolution of the dark matter distribution at the galactic center.
AB  - Annihilation radiation from neutralino dark matter at the Galactic center (GC)
      would be greatly enhanced if the dark matter were strongly clustered around the
      supermassive black hole (SBH). The existence of a dark matter "spike" is made
      plausible by the observed, steeply rising stellar density near the GC SBH. Here
      the time-dependent equations describing gravitational interaction of the dark
      matter with the stars are solved. Scattering of dark matter particles by stars
      would substantially lower the dark matter density near the GC SBH over 10 Gyr,
      due both to kinetic heating and to capture of dark matter particles by the SBH.
      This evolution implies a decrease by several orders of magnitude in the
      observable flux of annihilation products compared with models that associate a
      steep, dark matter spike with the SBH.

PMID- 15169339
TI  - Lower limits on R-parity-violating couplings in supersymmetric models with light
      squarks.
AB  - We interpret the results of searches for strongly interacting massive particles
      to place absolute lower limits on R-parity-violating couplings for squarks with
      mass (m(q) below 100 GeV. Recent searches for anomalous isotopes require that
      there be a baryon-number-violating or lepton-number-violating coupling larger
      than 10(-22)-10(-21) if m(q)>18 GeV. Using data from searches for stable
      particles at the CERN Large Electron Positron Collider (LEP) we demonstrate that
      this lower limit increases by 14 orders of magnitude, to an R-parity-violating
      coupling larger than 10(-8)-10(-7) for any squarks of mass less than 90 GeV. In
      the presence of an R-parity-violating coupling of this magnitude, neutralinos
      cannot explain the dark matter density in the Universe.

PMID- 15169341
TI  - Supersymmetric right-handed s-b flavor mixing: implications of B(0)-->phiK(S)
      anomaly for B factories and colliders.
AB  - Two recent experimental developments, when combined, may have far-reaching
      implications. S(phiK(S))<0, if confirmed, would imply large s-b mixing, a new CP
      phase, and right-handed dynamics. Large Deltam(B(s)) would be likely, making the
      B(s) program at hadron machines difficult. Reconstruction of B vertex from K(S)
      at B factories, as shown by BaBar's first measurement of SK(S)(pi(0)), makes
      SK(S)(pi(0)gamma) in B-->K(*0)gamma accessible. This would be a boon for B
      factory upgrades. Supersymmetric Abelian flavor symmetry, independently
      motivated, can realize all of this with a light sb(1) squark. B factory and
      collider studies of flavor, CP and supersymmetry, may not be what we had
      expected.

PMID- 15169342
TI  - Model-independent results for SU(3) violation in light-cone distribution
      functions.
AB  - Using chiral symmetry we investigate the leading SU(3) violation in light-cone
      distribution functions phi(M)(x) of the pion, kaon, and eta. It is shown that
      terms nonanalytic in the quark masses do not affect the shape, and only appear in
      the decay constants. Predictive power is retained including the leading analytic
      m(q) operators. With the symmetry violating corrections we derive useful model
      independent relations between phi(pi),phi(eta),phiK+(,K0), and phiK(0)(,K-).
      Using the soft-collinear effective theory we discuss how factorization generates
      the subleading chiral coefficients.

PMID- 15169344
TI  - Exclusive measurement of quasifree proton-neutron bremsstrahlung.
AB  - Data on proton-neutron bremsstrahlung have been obtained from a measurement of
      the quasifree breakup channel in proton-deuteron bremsstrahlung. This high
      precision measurement, with an incident proton energy of 190 MeV, is fully
      exclusive; i.e., the protons, the neutron, and the photon have been detected. The
      quasifree differential cross sections obtained are compared with microscopic
      calculations and calculations based on soft-photon models. There are sizable
      differences between the models and also between the models and the data obtained
      for this simple process.

PMID- 15169345
TI  - Supersymmetric patterns in the pseudospin, spin, and coulomb limits of the dirac
      equation with scalar and vector potentials.
AB  - We show that the Dirac equation in (3+1) dimensions gives rise to supersymmetric
      patterns when the scalar and vector potentials are (i). Coulombic with arbitrary
      strengths or (ii). when their sum or difference is a constant, leading to
      relativistic pseudospin and spin symmetries. The conserved quantities and the
      common intertwining relation responsible for such patterns are discussed.

PMID- 15169346
TI  - Multiphoton double ionization via field-independent resonant excitation.
AB  - The double ionization of xenon in the multiphoton regime has been studied at two
      wavelengths (0.77 and 0.79 microm) using an electron-ion coincidence technique
      and an intensity binned ion ratio method. Sharp resonant structures in the
      electron energy distribution correlated with the doubly charged ion, as well as a
      wavelength dependence of the Xe(2+)/Xe(+) ratio provides new insights. A
      mechanism involving the shelving of population in Rydberg states followed by
      excitation of a core electron is proposed.

PMID- 15169347
TI  - Spontaneous emission lifetime of a single trapped Ca(+) ion in a high finesse
      cavity.
AB  - We investigate the spontaneous emission lifetime of a single trapped (40)Ca+ ion
      placed at different positions in the vacuum standing wave inside a high finesse
      cavity which is stabilized to the atomic transition. The lifetime is measured by
      quantum state detection after pi-pulse excitation. The result for the natural
      lifetime of the D(5/2) metastable state of 1161(22) ms agrees, within 1 standard
      deviation, with the most precise published value. We observe a reduction of the
      spontaneous emission lifetime of approximately 15% in the node of the vacuum
      field.

PMID- 15169348
TI  - Dissociation energies of molecular hydrogen and the hydrogen molecular ion.
AB  - We have obtained improved values for the dissociation energies of molecular
      hydrogen and its ion by using a high-resolution pulse-amplified laser to probe
      the second dissociation limit. The onset of the vibrational continuum is observed
      by state-selective detection of the atomic products of dissociation, and several
      auxiliary measurements link the results to the ground state. The dissociation
      energies are accurate to 0.010-0.026 cm(-1), improving previous measurements by a
      factor of 3-7. Agreement with ab initio calculations is good for H2, D2, and
      their ions, but not for HD and HD+.

PMID- 15169349
TI  - Electron-electron interaction in strong electromagnetic fields: the two-electron
      contribution to the ground-state energy in He-like uranium.
AB  - Radiative recombination transitions into the ground state of cooled bare and
      hydrogenlike uranium ions were measured at the storage ring ESR. By comparing the
      corresponding x-ray centroid energies, this technique allows for a direct
      measurement of the electron-electron contribution to the ionization potential in
      the heaviest He-like ions. For the two-electron contribution to the ionization
      potential of He-like uranium we obtain a value of 2248+/-9 eV. This represents
      the most accurate determination of two-electron effects in the domain of high-Z
      He-like ions, and the accuracy reaches already the size of the specific two
      electron radiative QED corrections.

PMID- 15169350
TI  - Coherence in microchip traps.
AB  - We report the coherent manipulation of internal states of neutral atoms in a
      magnetic microchip trap. Coherence lifetimes exceeding 1 s are observed with
      atoms at distances of 5-130 microm from the microchip surface. The coherence
      lifetime in the chip trap is independent of atom-surface distance within our
      measurement accuracy and agrees well with the results of similar measurements in
      macroscopic magnetic traps. Because of the absence of surface-induced
      decoherence, a miniaturized atomic clock with a relative stability in the 10(-13)
      range can be realized. For applications in quantum information processing, we
      propose to use microwave near fields in the proximity of chip wires to create
      potentials that depend on the internal state of the atoms.

PMID- 15169352
TI  - Quantum interference of ultrastable twin optical beams.
AB  - We report the first measurement of the quantum phase-difference noise of an
      ultrastable nondegenerate optical parametric oscillator that emits twin beams
      classically phase locked at exact frequency degeneracy. The measurement
      illustrates the property of a lossless balanced beam splitter to convert number
      difference squeezing into phase-difference squeezing, and thus provides indirect
      evidence for Heisenberg-limited interferometry using twin beams. This experiment
      is a generalization of the Hong-Ou-Mandel interference effect for continuous
      variables and constitutes a milestone towards continuous-variable entanglement of
      bright, ultrastable nondegenerate beams.

PMID- 15169353
TI  - Electromagnetically induced transparency with squeezed vacuum.
AB  - The squeezed vacuum resonant on the (87)Rb D1 line (probe light) was injected
      into an optically dense rubidium gas cell with a coherent light (control light).
      The output probe light maintained its quadrature squeezing within the
      transparency window caused by the electromagnetically induced transparency (EIT).
      The results reported here are the first realization of EIT in the full quantum
      regime.

PMID- 15169354
TI  - Sub- and superluminal propagation of intense pulses in media with saturated and
      reverse absorption.
AB  - We develop models for the propagation of intense pulses in solid state media
      which can have either saturated absorption or reverse absorption. We model
      subluminal propagation in ruby and superluminal propagation in alexandrite as
      three and four level systems, respectively, coupled to Maxwell's equations. We
      present results well beyond the traditional pump-probe approach and explain the
      experiments of Bigelow et al. [Phys. Rev. Lett. 90, 113903 (2003)]Science 301,
      200 (2003)]] on solid state materials.

PMID- 15169355
TI  - Rare events and scale-invariant dynamics of perturbations in delayed chaotic
      systems.
AB  - We study the dynamics of perturbations in time-delay dynamical systems. Using a
      suitable space-time coordinate transformation, we find that the time evolution of
      the linearized perturbations (Lyapunov vector) can be described by the linear
      Zhang surface growth model [J. Phys. (France) 51, 2129 (1990)]], which is known
      to describe surface roughening driven by power-law distributed noise. As a
      consequence, Lyapunov vector dynamics is dominated by rare random events that
      lead to non-Gaussian fluctuations and multiscaling properties.

PMID- 15169351
TI  - Collective excitations of a degenerate gas at the BEC-BCS crossover.
AB  - We study collective excitation modes of a fermionic gas of (6)Li atoms in the BEC
      BCS crossover regime. While measurements of the axial compression mode in the
      cigar-shaped trap close to a Feshbach resonance confirm theoretical expectations,
      the radial compression mode shows surprising features. In the strongly
      interacting molecular BEC regime, we observe a negative frequency shift with
      increasing coupling strength. In the regime of a strongly interacting Fermi gas,
      an abrupt change in the collective excitation frequency occurs, which may be a
      signature for a transition from a superfluid to a collisionless phase.

PMID- 15169356
TI  - Huge fluctuations in weight measurements at the bottom of a two-dimensional
      vertical sheet of grains.
AB  - Weight measurements at the bottom of a quasi-2D vertical sheet of static
      cohesionless grains are carried out. The grains are held between two coaxial
      cylinders. This peculiar setup allows us to set either periodic or fixed lateral
      boundary conditions. Huge relative fluctuations in weight measurements appear in
      case of fixed lateral walls. This may be related to some indetermination in the
      mobilization state of friction forces on lateral walls. This argument would hold
      for any piling, but would lead to huge fluctuations in 2D systems only, because
      of averaging effects in 3D.

PMID- 15169357
TI  - Ultralow emittance, multi-MeV proton beams from a laser virtual-cathode plasma
      accelerator.
AB  - The laminarity of high-current multi-MeV proton beams produced by irradiating
      thin metallic foils with ultraintense lasers has been measured. For proton
      energies >10 MeV, the transverse and longitudinal emittance are, respectively,
      <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as
      10(4)-fold better than conventional accelerator beams. The fast acceleration
      being electrostatic from an initially cold surface, only collisions with the
      accelerating fast electrons appear to limit the beam laminarity. The ion beam
      source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.

PMID- 15169358
TI  - Spectral distributions of thomson-scattered photons from high-intensity pulsed
      lasers.
AB  - General formulas for the far-field spectral distribution of photons Thomson
      scattered by a single electron have been obtained. Effects due to the pulsed
      nature of the laser beam are explicitly allowed, simultaneously with intensity
      high enough that harmonic generation is possible. For realistic pulsed photon
      beams, the spectrum of backscattered radiation is considerably broadened because
      of changes in the longitudinal velocity of the electrons during the pulse. Such
      ponderomotive broadening is especially pronounced at higher harmonics, eventually
      leading to a continuous emission spectrum.

PMID- 15169360
TI  - Electron acceleration in an ultraintense-laser-illuminated capillary.
AB  - An ultraintense laser injected a 10 J of power at 1.053 microm in 0.5 ps into a
      glass capillary of 1 cm long and 60 microm in diameter and accelerated plasma
      electrons to 100 MeV. One- and two-dimensional particle codes describe wakefields
      with 10 GV/m gradient excited behind the laser pulse, which are guided by a
      plasma density channel far beyond the Rayleigh range. The blueshift of the laser
      spectrum supports that a plasma of 10(16) cm(-3) is inside the capillary. A bump
      at the high energy tail suggests the electron trapping in the wakefield.

PMID- 15169359
TI  - Effects of nonuniform illumination on implosion asymmetry in direct-drive
      inertial confinement fusion.
AB  - Target areal density (rhoR) asymmetries in OMEGA direct-drive spherical
      implosions are studied. The rms variation <deltarhoR>/<rhoR> for low-mode-number
      structure is approximately proportional to the rms variation of on-target laser
      intensity <deltaI>/<I> with an amplification factor of approximately 1/2(C(r)-1),
      where C(r) is the capsule convergence ratio. This result has critical
      implications for future work on the National Ignition Facility as well as OMEGA.

PMID- 15169340
TI  - Measurements of branching fractions and CP-violating asymmetries in B meson
      decays to charmless two-body states containing a K(0).
AB  - We present measurements of branching fractions and CP-violating asymmetries in
      decays of B mesons to two-body final states containing a K0. The results are
      based on a data sample of approximately 88 x 10(6) Upsilon(4S)-->BB decays
      collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at
      SLAC. We measure B(B+-->K(0)pi(+))=(22.3+/-1.7+/-1.1)x10(-6), B(B0-
      >K(0)pi(0)=(11.4+/-1.7+/-0.8)x10(-6), B(B+-->K(0)K+)<2.5 x 10(-6), and B(B0-
      >K(0)K(0)<1.8 x 10(-6), where the first uncertainty is statistical and the second
      is systematic, and the upper limits are at the 90% confidence level. In addition,
      the following CP-violating asymmetries have been measured: A(CP)(B+-->K(0)pi(+))=
      0.05+/-0.08+/-0.01 and A(CP)(B0-->K(0)pi(0)=0.03+/-0.36+/-0.11.

PMID- 15169361
TI  - Resonant heating of a cluster plasma by intense laser light.
AB  - The heating of a single argon (Ar) cluster by a strong laser field is studied
      using an electrostatic particle-in-cell code for a range of intensities and
      cluster sizes. Heating is dominated by a nonlinear resonant absorption process
      involving energetic electrons transiting through the cluster. This process gives
      rise to a threshold in field strength for strong absorption and controls the
      dielectric properties of the cluster.

PMID- 15169363
TI  - Experimental verification of the mechanisms for nonlinear harmonic growth and
      suppression by harmonic injection in a traveling wave tube.
AB  - Understanding the generation and growth of nonlinear harmonic (and
      intermodulation) distortion in microwave amplifiers such as traveling wave tubes
      (TWTs), free electron lasers (FELs), and klystrons is of current research
      interest. Similar to FELs, the nonlinear harmonic growth rate scales with the
      harmonic number in TWTs. In klystrons, the wave number scaling applies to the
      nonlinear harmonic bunching and associated nonlinear space-charge waves. Using a
      custom-modified TWT that has sensors along the helix, we provide the first
      experimental confirmation of the scaling of nonlinear harmonic growth rate and
      wave number in TWTs. These scalings of a nonlinearly generated harmonic mode
      versus an injected linear harmonic mode imply that suppression by harmonic
      injection occurs at a single axial position that can be located as desired by
      changing the injected amplitude and phase.

PMID- 15169362
TI  - Current dynamics during disruptions in large tokamaks.
AB  - Self-consistent modeling of the evolution of the plasma current during
      disruptions in large tokamaks is presented, taking into account both the
      generation of runaway electrons and their backreaction on the electric field. It
      is found that the current profile changes dramatically, so that the
      postdisruption current carried by runaway electrons is much more peaked than the
      thermal predisruption current. Although only a fraction of the thermal current is
      converted into runaway electrons, the central current density increases
      significantly for typical parameters in JET and ITER. It is also shown that the
      radial runaway profile can easily become filamented in the radial direction.

PMID- 15169365
TI  - Force on a charged test particle in a collisional flowing plasma.
AB  - The force on a charged test particle embedded in a flowing (electron-ion) plasma
      is calculated using the linear dielectric response formalism. This approach
      allows us to take into account ion-neutral collisions self-consistently. The
      effect of collisions on the ion drag force is analyzed. It is shown that
      collisions can play a major role and can enhance the force substantially.

PMID- 15169364
TI  - Effect of nonlocal transport on heat-wave propagation.
AB  - We present the first direct measurements of spatially and temporally resolved
      temperature and density profiles produced by nonlocal transport in a laser
      plasma. Absolutely calibrated measurements have been performed by Rayleigh
      scattering and by resolving the ion-acoustic wave spectra across the plasma
      volume with Thomson scattering. We find that the electron temperature and density
      profiles disagree with flux-limited models, but are consistent with nonlocal
      transport modeling.

PMID- 15169343
TI  - Measurement of the branching fractions and CP asymmetry of B--->D(0)((CP))K-
      decays with the BABAR detector.
AB  - We present a study of B--->D(0)(CP)K- decays, where D(0)(CP) is reconstructed in
      CP-even channels, based on a sample of 88.8 x 10(6) Upsilon(4S)-->BB decays
      collected with the BABAR detector at the PEP-II e(+)e(-) storage ring. We measure
      the ratio of Cabibbo-suppressed to Cabibbo-favored branching fractions B(B--
      >D(0)(CP)K-)/B(B--->D(0)(CP)pi(-))=[8.8+/-1.6(stat)+/-0.5(syst)]x10(-2) and the
      CP asymmetry A(CP)=0.07+/-0.17(stat)+/-0.06(syst). We also measure B(B--->D0K
      )/B(B--->D0pi(-))=[8.31+/-0.35(stat)+/-0.20(syst)]x10(-2) using a sample of 61.0
      x 10(6) BB pairs.

PMID- 15169366
TI  - Site-selective holographic imaging of iron arrangements in magnetite.
AB  - Complex gamma-ray holograms were recorded by tuning to the nuclear absorption
      lines of 57Fe in magnetite corresponding to different hyperfine fields. The
      numerical reconstruction of the holograms to real space provided three
      dimensional images of local iron arrangements in octahedral and tetrahedral
      sublattices of magnetite. This direct site-selective imaging of atomic structure
      was performed using a tabletop experimental setup.

PMID- 15169367
TI  - Capillary condensation in liquid-crystal colloids.
AB  - We study capillary condensation between two spherical particles dispersed in the
      isotropic phase of a nematic liquid crystal. Within the Landau-de Gennes theory,
      we calculate interaction energies due to the formation of capillary bridges that
      reproduce experimental observations. Close to the critical point of the
      transition line separating the no-bridge from the bridge configuration,
      fluctuations in the particle cluster might be described by an effective two-state
      system. We show that the transition line vanishes for small particles and that
      the shape of the interaction potential depends on particle size.

PMID- 15169369
TI  - Contrast reversal and shape changes of atomic adsorbates measured with scanning
      tunneling microscopy.
AB  - Systematic, quantitative comparisons between scanning tunneling microscopy (STM)
      experiments and first principles simulations of O(2 x 2)/Ru(0001) have been
      performed. The shape of the atomic adsorbates in the images depends strongly on
      the tunneling resistance and changes reversibly from circular (high resistance)
      to triangular (low resistance). In addition, after adsorption of oxygen on the
      STM tip we observe a contrast reversal on the surface, confirmed by extensive
      numerical simulations.

PMID- 15169368
TI  - Interfacial melting of ice in contact with SiO(2).
AB  - The physical behavior of condensed matter can be drastically altered in the
      presence of interfaces. Using a high-energy x-ray transmission-reflection scheme,
      we have studied ice-SiO2 model interfaces. We observed the formation of a
      quasiliquid layer below the bulk melting temperature and determined its thickness
      and density as a function of temperature. The quasiliquid layer has stronger
      correlations than water and a large density close to rho(HDA)=1.17 g/cm(3) of
      high-density amorphous ice suggesting a structural relationship with the
      postulated high-density liquid phase of water.

PMID- 15169370
TI  - Vibronic states in single molecule electron transport.
AB  - A scanning tunneling microscope was used to study the electron transport through
      individual copper phthalocyanine molecules adsorbed on an ultrathin Al(2)O(3)
      film grown on a NiAl(110) surface. The differential conductance spectra display
      series of equally spaced features, which are attributed to vibronic states of
      individual molecules. The coupling of the electron current to the vibronic modes
      was observed to depend on the structures of the adsorbed molecules. Vibronic
      features were not observed for molecules adsorbed on the bare NiAl(110) surface
      due to spectral broadening.

PMID- 15169371
TI  - Planar vanadium oxide clusters: two-dimensional evaporation and diffusion on
      Rh(111).
AB  - The formation of novel vanadium oxide cluster molecules by oxidative two
      dimensional evaporation from vanadium oxide nanostructures is reported on a
      Rh(111) metal surface. The structure and stability of the planar V6O12 clusters
      and the physical origin of their 2D evaporation process have been elucidated by
      high-resolution scanning tunneling microscopy (STM) and ab initio density
      functional theory calculations. The surface diffusion of the clusters has been
      followed in elevated-temperature STM experiments, and the diffusion parameters
      have been extracted, indicating diffusion by hopping of the entire surface
      stabilized cluster units.

PMID- 15169373
TI  - Positive cross correlations in a three-terminal quantum dot with ferromagnetic
      contacts.
AB  - We study current fluctuations in an interacting three-terminal quantum dot with
      ferromagnetic leads. For appropriately polarized contacts, the transport through
      the dot is governed by dynamical spin blockade, i.e., a spin-dependent bunching
      of tunneling events not present in the paramagnetic case. This leads, for
      instance, to positive zero-frequency cross correlations of the currents in the
      output leads even in the absence of spin accumulation on the dot. We include the
      influence of spin-flip scattering and identify favorable conditions for the
      experimental observation of this effect with respect to polarization of the
      contacts and tunneling rates.

PMID- 15169372
TI  - Shot noise spectrum of open dissipative quantum two-level systems.
AB  - We study the current noise spectrum of qubits under transport conditions in a
      dissipative bosonic environment. We combine (non-)Markovian master equations with
      correlation functions in Laplace space to derive a noise formula for both weak
      and strong coupling to the bath. The coherence-induced reduction of noise is
      diminished by weak dissipation and/or a large level separation (bias). For weak
      dissipation, we demonstrate that the dephasing and relaxation rates of the two
      level systems can be extracted from noise. In the strong dissipation regime, the
      localization-delocalization transition becomes visible in the low-frequency
      noise.

PMID- 15169375
TI  - Suppression of superconductivity in granular metals.
AB  - We investigate the suppression of the superconducting transition temperature due
      to Coulomb repulsion in granular metallic systems at large tunneling conductance
      between the grains, g(T)>>1. We find the correction to the superconducting
      transition temperature for 3D granular samples and films. We demonstrate that,
      depending on the parameters of superconducting grains, the corresponding granular
      samples can be divided into two groups: (i). the granular samples that belong to
      the first group may have only insulating or superconducting states at zero
      temperature depending on the bare intergranular tunneling conductance g(T), while
      (ii). the granular samples that belong to the second group in addition have an
      intermediate metallic phase where superconductivity is suppressed while the
      effects of the Coulomb blockade are not yet strong.

PMID- 15169374
TI  - Circular dichroism in angle-resolved photoemission spectra of under- and
      overdoped Pb-Bi2212.
AB  - We use angle-resolved photoemission with circularly polarized excitation to
      demonstrate that in the 5 x 1 superstructure-free
      (Pb,Bi)(2)Sr(2)CaCu(2)O(8+delta) (Pb-Bi2212) material there are no signatures of
      time-reversal symmetry breaking in the sense of the criteria developed earlier
      [Nature (London) 416, 610 (2002)]]. The dichroic signal retains reflection
      antisymmetry as a function of temperature and doping and in all mirror planes,
      precisely defined by the experimental dispersion at low energies. The obtained
      results demonstrate that the signatures of time-reversal symmetry violation in
      pristine Bi2212, as determined by angle-resolved photoemission spectroscopy, are
      not a universal feature of all cuprate superconductors.

PMID- 15169376
TI  - Commensurate-incommensurate magnetic phase transition in magnetoelectric single
      crystal LiNiPO(4).
AB  - Neutron scattering studies of single crystal LiNiPO4 reveal a spontaneous first
      order commensurate-incommensurate magnetic phase transition. Short- and long
      range incommensurate phases are intermediate between the high temperature
      paramagnetic and the low temperature antiferromagnetic phases. The modulated
      structure has a predominant antiferromagnetic component, giving rise to satellite
      peaks in the vicinity of the fundamental antiferromagnetic Bragg reflection, and
      a ferromagnetic component, giving rise to peaks at small momentum transfers
      around the origin at (0,+/-Q,0). The wavelength of the modulated magnetic
      structure varies continuously with temperature. It is argued that the
      incommensurate short- and long-range phases are due to spin-dimensionality
      crossover from a continuous to the discrete Ising state.

PMID- 15169377
TI  - Field-induced magnetic order and simultaneous lattice deformation in TlCuCl(3).
AB  - We report the results of Cu and Cl nuclear magnetic resonance experiments and
      thermal expansion measurements in magnetic fields in the coupled dimer spin
      system TlCuCl3. We found that the field-induced antiferromagnetic transition as
      confirmed by the splitting of NMR lines is slightly discontinuous. The abrupt
      change of the electric field gradient at the Cl sites, as well as the sizable
      change of the lattice constants, across the phase boundary indicate that the
      magnetic order is accompanied by simultaneous lattice deformation.

PMID- 15169378
TI  - Domain-wall dynamics and spin-wave excitations with spin-transfer torques.
AB  - A generalization of spin-transfer torques in ferromagnetic structures is
      proposed. For a spatially nonuniform magnetization, the spin torque has a form
      nearly identical to that in magnetic multilayers. We show that the domain-wall
      motion driven by the current has many unique features that do not exist in the
      conventional domain-wall motion driven by a magnetic field. We also demonstrate
      that the spin torque can generate bulk and surface spin excitations that have
      been seen in point-contact experiments.

PMID- 15169379
TI  - Finite-size effects in single chain magnets: an experimental and theoretical
      study.
AB  - The problem of finite-size effects in s=1/2 Ising systems showing slow dynamics
      of the magnetization is investigated introducing diamagnetic impurities in a Co2+
      radical chain. The static magnetic properties have been measured and analyzed
      considering the peculiarities induced by the ferrimagnetic character of the
      compound. The dynamic susceptibility shows that an Arrhenius law is observed with
      the same energy barrier for the pure and the doped compounds while the prefactor
      decreases, as theoretically predicted. Multiple spin reversal has also been
      investigated.

PMID- 15169380
TI  - S mixing and quantum tunneling of the magnetization in molecular nanomagnets.
AB  - The role of S mixing in the quantum tunneling of the magnetization in nanomagnets
      has been investigated. We show that the effect on the tunneling frequency is huge
      and that the discrepancy (more than 3 orders of magnitude in the tunneling
      frequency) between spectroscopic and relaxation measurements in Fe(8) can be
      resolved if S mixing is taken into account.

PMID- 15169381
TI  - In situ diagnostics of the crystalline nature of single organic nanocrystals by
      nonlinear microscopy.
AB  - We elucidate the crystalline nature and the three-dimensional orientation of
      isolated organic nanocrystals embedded in a sol-gel matrix, using a polarized
      nonlinear microscopy technique that combines two-photon fluorescence and second
      harmonic generation. This technique allows the distinction between
      monocrystalline structures and nanoscale polycrystalline aggregates responsible
      for incoherent second harmonic signals.

PMID- 15169382
TI  - Different look at the spin state of Co(3+) ions in a CoO(5) pyramidal
      coordination.
AB  - Using soft-x-ray absorption spectroscopy at the Co L(2,3) and O K edges, we
      demonstrate that the Co3+ ions with the CoO5 pyramidal coordination in the
      layered Sr2CoO3Cl compound are unambiguously in the high spin state. Our result
      questions the reliability of the spin state assignments made so far for the
      recently synthesized layered cobalt perovskites and calls for a reexamination of
      the modeling for the complex and fascinating properties of these new materials.

PMID- 15169383
TI  - Effective quantum spin systems with trapped ions.
AB  - We show that the physical system consisting of trapped ions interacting with
      lasers may undergo a rich variety of quantum phase transitions. By changing the
      laser intensities and polarizations the dynamics of the internal states of the
      ions can be controlled, in such a way that an Ising or Heisenberg-like
      interaction is induced between effective spins. Our scheme allows us to build an
      analogue quantum simulator of spin systems with trapped ions, and observe and
      analyze quantum phase transitions with unprecedented opportunities for the
      measurement and manipulation of spins.

PMID- 15169384
TI  - Pulling tethers from adhered vesicles.
AB  - The competition between adhesion and tether formation in bound vesicles is
      investigated. A theoretical model is developed in which tethers are induced by
      the application of a pulling force to the top of a strongly adhered vesicle. A
      critical onset force is identified where the tether spontaneously appears as part
      of a first order shape transition. Further growth of the tether initiates a
      detachment process that culminates in a continuous unbinding of the vesicle at a
      finite detachment force. Both critical forces, as well as all shape parameters,
      are calculated as a function of the reduced volume and the strength of adhesive
      potential.

PMID- 15169385
TI  - Quantum control by ultrafast polarization shaping.
AB  - We demonstrate that the use of time-dependent light polarization opens a new
      level of control over quantum systems. With potassium dimer molecules from a
      supersonic molecular beam, we show that a polarization-shaped laser pulse
      increases the ionization yield beyond that obtained with an optimally shaped
      linearly polarized laser pulse. This is due to the different multiphoton
      ionization pathways in K2 involving dipole transitions which favor different
      polarization directions of the exciting laser field. This experiment is a
      qualitative extension of quantum control mechanisms which opens up new directions
      giving access to the three-dimensional temporal response of molecular systems.

PMID- 15169386
TI  - Comment on interferometric detection of optical phase shifts at the heisenberg
      limit.

PMID- 15169388
TI  - Comment on vortex liquid crystal in anisotropic type II superconductors.

PMID- 15169390
TI  - Observation of reduced three-body recombination in a correlated 1D degenerate
      Bose gas.
AB  - We investigate the correlation properties of a one-dimensional interacting Bose
      gas by loading a magnetically trapped 87Rb Bose-Einstein condensate (BEC) into a
      deep two-dimensional optical lattice. We measure the three-body recombination
      rate for both the BEC in the magnetic trap and the BEC loaded into the optical
      lattice. The recombination rate coefficient is a factor of 7 smaller in the
      lattice, which we interpret as a reduction in the local three-body correlation
      function in the 1D case. This is a signature of correlation intermediate between
      that of the uncorrelated, phase coherent, 1D, mean-field regime and the strongly
      correlated Tonks-Girardeau regime.

PMID- 15169391
TI  - Measuring a photonic qubit without destroying it.
AB  - Measuring the polarization of a single photon typically results in its
      destruction. We propose, demonstrate, and completely characterize a quantum
      nondemolition (QND) scheme for realizing such a measurement nondestructively.
      This scheme uses only linear optics and photodetection of ancillary modes to
      induce a strong nonlinearity at the single-photon level, nondeterministically. We
      vary this QND measurement continuously into the weak regime and use it to perform
      a nondestructive test of complementarity in quantum mechanics. Our scheme
      realizes the most advanced general measurement of a qubit to date: it is
      nondestructive, can be made in any basis, and with arbitrary strength.

PMID- 15169393
TI  - Kerr black holes in horizon-generating form.
AB  - New coordinates are given which describe nondegenerate Kerr black holes in dual
      null foliations based on the outer (or inner) horizons, generalizing the Kruskal
      form for Schwarzschild black holes. The construction involves an area radius for
      the transverse surfaces and a generalization of the Regge-Wheeler radial
      function, both functions of the original radial coordinate only.

PMID- 15169392
TI  - Optical torque wrench: angular trapping, rotation, and torque detection of quartz
      microparticles.
AB  - We describe an apparatus that can measure the instantaneous angular displacement
      and torque applied to a quartz particle which is angularly trapped. Torque is
      measured by detecting the change in angular momentum of the transmitted trap
      beam. The rotational Brownian motion of the trapped particle and its power
      spectral density are used to determine the angular trap stiffness. The apparatus
      features a feedback control that clamps torque or other rotational quantities.
      The torque sensitivity demonstrated is ideal for the study of known biological
      molecular motors.

PMID- 15169394
TI  - Structure function scaling in compressible super-Alfvenic MHD turbulence.
AB  - Supersonic turbulent flows of magnetized gas are believed to play an important
      role in the dynamics of star-forming clouds in galaxies. Understanding
      statistical properties of such flows is crucial for developing a theory of star
      formation. In this Letter we propose a unified approach for obtaining the
      velocity scaling in compressible and super-Alfvenic turbulence, valid for the
      arbitrary sonic Mach number, M(S). We demonstrate with numerical simulations that
      the scaling can be described with the She-Leveque formalism, where only one
      parameter, interpreted as the Hausdorff dimension of the most intense dissipative
      structures, needs to be varied as a function of M(S). Our results thus provide a
      method for obtaining the velocity scaling in interstellar clouds once their Mach
      numbers have been inferred from observations.

PMID- 15169395
TI  - Solving the cooling flow problem of galaxy clusters by dark matter neutralino
      annihilation.
AB  - Recent x-ray observations revealed that strong cooling flow of intracluster gas
      is not present in galaxy clusters, even though it is predicted theoretically if
      there is no additional heating source. I show that relativistic particles
      produced by dark matter neutralino annihilation in cluster cores provide a
      sufficient heating source to suppress the cooling flow, under reasonable
      astrophysical circumstances including adiabatic growth of central density
      profile, with appropriate particle physics parameters for dark matter
      neutralinos. In contrast to other astrophysical heat sources, such as active
      galactic nuclei, this process is a steady and stable feedback over cosmological
      time scales after turned on.

PMID- 15169396
TI  - 1+1 dimensional compactifications of string theory.
AB  - We argue that stable, maximally symmetric compactifications of string theory to
      1+1 dimensions are in conflict with holography. In particular, the finite horizon
      entropies of the Rindler wedge in 1+1 dimensional Minkowski and anti-de Sitter
      space, and of the de Sitter horizon in any dimension, are inconsistent with the
      symmetries of these spaces. The argument parallels one made recently by the same
      authors, in which we demonstrated the incompatibility of the finiteness of the
      entropy and the symmetries of de Sitter space in any dimension. If the horizon
      entropy is either infinite or zero, the conflict is resolved.

PMID- 15169397
TI  - Precise mass measurement of 68Se, a waiting-point nuclide along the rp process.
AB  - Mass measurements of 68Ge, 68As, and 68Se have been obtained with the Canadian
      Penning Trap mass spectrometer. The results determine the mass excess of 68Se as 
      54 232(19) keV, the first measurement with a precision and reliability sufficient
      to address the light-curve and energy output of x-ray bursts as well as the
      abundances of the elements synthesized. Under typical conditions used for
      modeling x-ray bursts, 68Se is found to cause a significant delay in the rp
      process nucleosynthesis.

PMID- 15169398
TI  - Density matrix perturbation theory.
AB  - An orbital-free quantum perturbation theory is proposed. It gives the response of
      the density matrix upon variation of the Hamiltonian by quadratically convergent
      recursions based on perturbed projections. The technique allows treatment of
      embedded quantum subsystems with a computational cost scaling linearly with the
      size of the perturbed region, O(N(pert.)), and as O(1) with the total system
      size. The method allows efficient high order perturbation expansions, as
      demonstrated with an example involving a 10th order expansion. Density matrix
      analogs of Wigner's 2n+1 rule are also presented.

PMID- 15169399
TI  - Ab initio linear scaling response theory: electric polarizability by perturbed
      projection.
AB  - A linear scaling method for calculation of the static ab initio response within
      self-consistent field theory is developed and applied to the calculation of the
      static electric polarizability. The method is based on the density matrix
      perturbation theory [Phys. Rev. Lett. 92, 193001 (2004)]], obtaining response
      functions directly via a perturbative approach to spectral projection. The
      accuracy and efficiency of the linear scaling method is demonstrated for a series
      of three-dimensional water clusters at the RHF/6-31G(**) level of theory. The
      locality of the response under a global electric field perturbation is
      numerically demonstrated by the approximate exponential decay of derivative
      density matrix elements.

PMID- 15169400
TI  - Calibrating dipolar interaction in an atomic condensate.
AB  - We reexamine the topic of a dipolar condensate with the recently derived more
      rigorous pseudopotential for dipole-dipole interaction [Phys. Rev. A 67, 033607
      (2003)]]. Based on the highly successful variational technique, we find that all
      dipolar effects estimated before (using the bare dipole-dipole interaction)
      become significantly larger, i.e., are amplified by the new velocity-dependent
      pseudopotential, especially in the limit of large or small trap aspect ratios.
      This result points to a promising prospect for detecting dipolar effects inside
      an atomic condensate.

PMID- 15169401
TI  - Homodyne tomography characterization and nonlocality of a dual-mode optical
      qubit.
AB  - A single photon, delocalized over two optical modes, is characterized by means of
      quantum homodyne tomography. The reconstructed four-dimensional density matrix
      extends over the entire Hilbert space and thus reveals, for the first time,
      complete information about the dual-rail optical quantum bit as a state of the
      electromagnetic field. The experimental data violate the Bell inequality albeit
      with a loophole similar to the detection loophole in photon counting experiments.

PMID- 15169403
TI  - BLOCH modes dressed by evanescent waves and the generalized Goos-Hanchen effect
      in photonic crystals.
AB  - It is common knowledge that in an infinite periodic medium, for instance, an
      infinite photonic crystal, the direction of propagation of a monochromatic wave
      packet is given by the normal to the isofrequency diagram. We show that this is
      no longer true in a finite size medium, due to the existence of evanescent waves
      near the interfaces of the photonic crystal. We derive a renormalized
      isofrequency diagram giving the correct direction. We give a physical
      interpretation, showing that this phenomenon can be considered as a generalized
      Goos-Hanchen effect.

PMID- 15169402
TI  - Controlling fast chaos in delay dynamical systems.
AB  - We introduce a novel approach for controlling fast chaos in time-delay dynamical
      systems and use it to control a chaotic photonic device with a characteristic
      time scale of approximately 12 ns. Our approach is a prescription for how to
      implement existing chaos-control algorithms in a way that exploits the system's
      inherent time delay and allows control even in the presence of substantial
      control-loop latency (the finite time it takes signals to propagate through the
      components in the controller). This research paves the way for applications
      exploiting fast control of chaos, such as chaos-based communication schemes and
      stabilizing the behavior of ultrafast lasers.

PMID- 15169404
TI  - Observation of optical precursors in water.
AB  - We observe the formation of optical precursors while propagating 540 fs pulses
      through 700 mm of deionized water. The launched pulses were strongly chirped to
      give them a bandwidth of approximately 60 nm to more readily excite the
      precursors. The precursors attenuated nonexponentially with distance.

PMID- 15169405
TI  - Time reversal of electromagnetic waves.
AB  - We report the first experimental demonstration of time-reversal focusing with
      electromagnetic waves. An antenna transmits a 1-micros electromagnetic pulse at a
      central frequency of 2.45 GHz in a high-Q cavity. Another antenna records the
      strongly reverberated signal. The time-reversed wave is built and transmitted
      back by the same antenna acting now as a time-reversal mirror. The wave is found
      to converge to its initial source and is compressed in time. The quality of
      focusing is determined by the frequency bandwidth and the spectral correlations
      of the field within the cavity.

PMID- 15169406
TI  - Dynamics of drag and force distributions for projectile impact in a granular
      medium.
AB  - Our experiments and molecular dynamics simulations on a projectile penetrating a
      two-dimensional granular medium reveal that the mean deceleration of the
      projectile is constant and proportional to the impact velocity. Thus, the time
      taken for a projectile to decelerate to a stop is independent of its impact
      velocity. The simulations show that the probability distribution function of
      forces on grains is time independent during a projectile's deceleration in the
      medium. At all times the force distribution function decreases exponentially for
      large forces.

PMID- 15169407
TI  - Nanoflares and MHD turbulence in coronal loops: a hybrid shell model.
AB  - A model to describe injection, due to footpoint motions, storage, and dissipation
      of MHD turbulence in coronal loops, is presented. The model is based on the use
      of the shell technique in the wave vector space applied to the set of reduced MHD
      equations. Numerical simulation showed that the energy injected is efficiently
      stored in the loop where a significant level of magnetic and velocity
      fluctuations is obtained. Nonlinear interactions among these fluctuations give
      rise to an energy cascade towards smaller scales where energy is dissipated in an
      intermittent fashion. The statistical analysis performed on the intermittent
      dissipative events compares well with all observed properties of nanoflare
      emission statistics.

PMID- 15169408
TI  - Plume motion and large-scale circulation in a cylindrical Rayleigh-Benard cell.
AB  - We used the time correlation of shadowgraph images to determine the angle Theta
      of the horizontal component of the plume velocity above (below) the center of the
      bottom (top) plate of a cylindrical Rayleigh-Benard cell of aspect ratio Gamma
      identical with D/L=1 (D is the diameter and L approximately 87 mm is the height)
      in the Rayleigh-number range 7 x 10(7)</=R</=3 x 10(9) for a Prandtl number
      sigma=6. We expect that Theta gives the direction of the large-scale circulation.
      It oscillates time periodically. Near the top and bottom plates Theta(t) has the
      same frequency but is anticorrelated.

PMID- 15169409
TI  - Clustering of plumes in turbulent convection.
AB  - Turbulent Rayleigh-Benard convection produces fields of intense updrafts and
      downdrafts that are responsible for much of the vertical heat transport. These
      structures, called plumes or thermals, have horizontal scales comparable to the
      thicknesses of the boundary layers in which they arise. In the three-dimensional
      numerical simulations reported here, we have observed that convective plumes
      organize themselves into clusters with horizontal scales that grow with time and
      reach the width of the computational domain. In this two-scale process, kinetic
      energy is transferred mainly to low horizontal wave numbers while the sizes of
      individual plumes remain on the scale of the boundary layer thickness.

PMID- 15169410
TI  - Suppression of the Rayleigh-Taylor instability due to self-radiation in a
      multiablation target.
AB  - A scheme to suppress the Rayleigh-Taylor instability has been investigated for a
      direct-drive inertial fusion target. In a high-Z doped-plastic target, two
      ablation surfaces are formed separately-one driven by thermal radiation and the
      other driven by electron conduction. The growth of the Rayleigh-Taylor
      instability is significantly suppressed on the radiation-driven ablation surface
      inside the target due to the large ablation velocity and long density scale
      length. A significant reduction of the growth rate was observed in simulations
      and experiments using a brominated plastic target. A new direct-drive pellet was
      designed using this scheme.

PMID- 15169411
TI  - Electronic and positronic guiding-center drift ions.
AB  - A novel type of guiding-center drift ion is described. These ions occur only in
      strong magnetic fields. They consist of a neutral atom to which either an
      electron or positron is weakly bound, at a sufficiently large radius that it may
      be described by ExB drift dynamics. Such ions may occur naturally in
      astrophysical plasmas and may have been formed in recent antihydrogen
      experiments, where their presence would provide proof that deeply bound H atoms
      are being created.

PMID- 15169412
TI  - Dissipation mechanisms near the superfluid 3He transition in aerogel.
AB  - We have investigated the dissipation (Q-1) using the torsion pendulum technique
      for pure 3He and 3He-4He mixtures in silica aerogel near the 3He superfluid
      transition (T(c)) in aerogel. With pure 3He the Q-1 decreases at the onset of
      superfluidity. When phase separated 3He-4He mixtures are introduced into the
      aerogel, the Q-1 does not decrease as rapidly and eventually increases for the
      highest 4He content. We provide a model for the related attenuation of transverse
      sound alpha that takes into account elastic and inelastic scattering processes
      and exhibits a decrease in alpha at T(c).

PMID- 15169413
TI  - Fluctuating lattice constants of indium under high pressure.
AB  - Recent high-pressure investigations of elemental In have yielded controversial
      results. We show that the observed high-pressure face-centered orthorhombic (fco)
      structure can be explained as an intermediate state between two body-centered
      tetragonal (bct) structures with different c/a ratios (c/a < square root [2] and
      c/a > square root [2], respectively). In a pressure range from about 50 to 200
      GPa these two bct structures correspond to local minima of the total energy with
      respect to orthorhombic distortion of the ground-state bct In structure. The fco
      saddle point represents a tiny barrier and even at low temperatures rapid
      structural fluctuations should occur. Such a situation has not been identified in
      any other elemental metal.

PMID- 15169414
TI  - Direct evidence for negative grain boundary potential in Ca-doped and undoped
      YBa2Cu3O7-x.
AB  - Using electron holography in a transmission electron microscope, we obtained
      direct evidence for the reduction of negative charge at grain boundary
      dislocations in Ca-doped YBa2Cu3O7 (YBCO) when compared to undoped YBCO. Because
      of the finite width of the valence band in the superconducting CuO2 planes, the
      negative grain boundary charge can lead to a depletion of electron holes
      available for superconductivity. A significant reduction in the size of the
      perturbed region in the Ca-doped samples appears to be the principal mechanism
      for the improved interfacial superconductivity.

PMID- 15169415
TI  - First-principles-based surface phase diagram of fully relaxed binary alloy
      surfaces.
AB  - The combination of density-functional theory (DFT) calculations of geometrically
      fully relaxed binary alloy surfaces with concepts from statistical physics is
      applied to construct a DFT-based phase diagram for a binary alloy surface. As a
      first example, we studied the appearance of Co antisite atoms at CoAl(100)
      surfaces. The structural parameters as multilayer relaxations, surface buckling,
      lateral order, and segregation profile of the predicted stable surface phases are
      in excellent agreement with experimental structure determinations applying low
      energy electron diffraction.

PMID- 15169416
TI  - Universal nuclear spin relaxation and long-range order in nematics strongly
      confined in mass fractal silica gels.
AB  - We show how the low-frequency dependence of the proton spin-lattice relaxation
      time T1(nu) of octylcyanobiphenyl liquid crystals confined in high-density silica
      gels evidences a long-range order nematic phase in spite of the strong
      confinement and random disorder of the gels. The universal value and frequency
      dependence observed, T1(nu) proportional, variant nu(2/3), is interpreted within
      a relaxation model due to director fluctuations in nematic liquid crystals
      confined to mass fractal porous media. The model provides a relation T1(nu)
      proportional, variant nu(2-d/2), giving a reliable value of the structural
      fractal dimension d(f)=2.67 for all the host silica gels.

PMID- 15169417
TI  - High-pressure melting of molybdenum.
AB  - The melting curve of the body-centered cubic (bcc) phase of Mo has been
      determined for a wide pressure range using both direct ab initio molecular
      dynamics simulations of melting as well as a phenomenological theory of melting.
      These two methods show very good agreement. The simulations are based on density
      functional theory within the generalized gradient approximation. Our calculated
      equation of state of bcc Mo is in excellent agreement with experimental data.
      However, our melting curve is substantially higher than the one determined in
      diamond anvil cell experiments up to a pressure of 100 GPa. An explanation is
      suggested for this discrepancy.

PMID- 15169418
TI  - Reentrant surface melting of colloidal hard spheres.
AB  - Concentrated suspensions of model colloidal hard spheres at a wall were studied
      in real space by means of time-resolved fluorescence confocal scanning
      microscopy. Both structure and dynamics of these systems differ dramatically from
      their bulk analogs (i.e., far away from a wall). In particular, systems that are
      a glass in the bulk show significant hexagonal order at a wall. Upon increasing
      the volume fraction of the colloids, a reentrant melting transition involving a
      hexatic structure is observed. The last observation points to two-dimensional
      behavior of matter at walls.

PMID- 15169419
TI  - Nonperturbative renormalization-group study of reaction-diffusion processes.
AB  - We generalize nonperturbative renormalization group methods to nonequilibrium
      critical phenomena. Within this formalism, reaction-diffusion processes are
      described by a scale-dependent effective action, the flow of which is derived. We
      investigate branching and annihilating random walks with an odd number of
      offspring. Along with recovering their universal physics (described by the
      directed percolation universality class), we determine their phase diagrams and
      predict that a transition occurs even in three dimensions, contrarily to what
      perturbation theory suggests.

PMID- 15169421
TI  - Pokrovsky-Talapov critical behavior and rough-to-rough ridges of the sigma3
      coincidence tilt boundary in Mo.
AB  - The as-grown shape of the cylindric tilt grain boundary (GB) in Mo bicrystals
      grown by the floating zone method has been studied with the electron
      backscattering diffraction method. The seed crystals were misoriented such that
      the coincidence site lattice (CSL) with lowest possible inverse density of
      coincidence sites, a Sigma=3 was grown. The flat (100)(Sigma3CSL) facets were
      observed forming smooth edges (no slope discontinuity) with rounded rough GB
      portions. Rough GBs curve away from the plane of the (100)(Sigma3CSL) facet as
      x(beta) with beta=1.69+/-0.07 on one side and beta=1.72+/-0.07 on the other side.
      Therefore, GB roughening belongs to the Pokrovsky-Talapov universality class.
      Slope discontinuities between two rounded rough GB portions were also observed.
      This is the first experimental observation of such first-order rough-to-rough
      ridges predicted by the Davidson-den-Nijs model.

PMID- 15169420
TI  - Capillary condensation in linear mesopores of different shape.
AB  - The hysteresis and kinetics of capillary condensation of N2 and Ar in linear
      mesopores, produced by etching of Si wafers, have been studied for different pore
      shapes, including the ink bottle geometry. Pore blocking has been observed in the
      solid state of the pore fillings, but not in the liquid state. We conclude that
      individual local geometries such as the pore mouth, a blind end, or a single
      constriction have no effect on the shape of sorption isotherms, that the pore
      space should be regarded as a statistical ensemble of pore segments with a lot of
      quenched disorder.

PMID- 15169422
TI  - Surface reconstruction and decahedral structure of bimetallic nanoparticles.
AB  - We report on energetic surface reconstruction phenomena observed on bimetallic
      nanoparticle systems of AuPd and AuCu, similar to a resolidification effect
      observed during the cooling process in lead clusters. These binary alloy
      nanoparticles show the fivefold edges truncated, resulting in [100] facets on
      decahedral structures, an effect largely envisioned and reported theoretically,
      with no experimental evidence so far. We demonstrate experimentally as well as by
      computational simulations that this new eutectic structure is favored in such
      nanoalloy systems.

PMID- 15169423
TI  - Excitons in carbon nanotubes: an ab initio symmetry-based approach.
AB  - The optical absorption spectrum of the carbon (4,2) nanotube is computed using an
      ab initio many-body approach which takes into account excitonic effects. We
      develop a new method involving a local basis set which is symmetric with respect
      to the screw-symmetry of the tube. Such a method has the advantages of scaling
      faster than plane-wave methods and allowing for a precise determination of the
      symmetry character of the single-particle states, two-particle excitations, and
      selection rules. The binding energy of the lowest, optically active states is
      approximately 0.8 eV. The corresponding exciton wave functions are delocalized
      along the circumference of the tube and localized in the direction of the tube
      axis.

PMID- 15169424
TI  - Many-body approximation scheme beyond GW.
AB  - We explore the combination of the extended dynamical mean field theory (EDMFT)
      with the GW approximation (GWA); the former sums the local contributions to the
      self-energies to infinite order in closed form and the latter handles the
      nonlocal ones to lowest order. We investigate the different levels of self
      consistency that can be implemented within this method by comparing to the exact
      quantum Monte Carlo solution of a finite-size model Hamiltonian. We find that
      using the EDMFT solution for the local self-energies as input to the GWA for the
      nonlocal self-energies gives the best result.

PMID- 15169425
TI  - Temperature dependence of the energy gap of semiconductors in the low-temperature
      limit.
AB  - The temperature dependence of the electronic states and energy gaps of
      semiconductors is an old but still important experimental and theoretical topic.
      Remarkably, extant results do not clarify the asymptotic T-->0 behavior. Recent
      breakthroughs in the spectroscopy of enriched 28Si allow us to measure changes in
      the band gap over the liquid 4He temperature range with an astounding precision
      of one part in 10(8), revealing a T4.0+/-0.2 decrease with increasing T. This is
      in excellent agreement with a theoretical argument predicting an exponent of 4.
      This power law should apply, in the low temperature limit, to the temperature
      dependence of the energies of all electronic states in semiconductors and
      insulators.

PMID- 15169426
TI  - Commensurate-incommensurate crossover of charge stripe in La2-xSrxNiO4 (x
      approximately 1/3).
AB  - The temperature (T) dependence of the charge-stripe order in La2-xSrxNiO4 has
      been investigated in the vicinity of x approximately 1/3 by synchrotron radiation
      x-ray diffraction measurements. With decreasing T, a prominent commensurate
      incommensurate (C-IC) crossover is observed in the x<1/3 region, while for the
      x>1/3 region the IC order is dominant over the whole T range. Such a C-IC
      crossover is interpreted as the entropy-driven self-doping of the charge stripes,
      and its x dependence indicates the clear electron-hole asymmetry with the x=1/3
      compound as the Mott insulator.

PMID- 15169427
TI  - Role of hybridization in NaxCoO2 and the effect of hydration.
AB  - Density functional theory is used to understand the electronic properties of
      Na(1/3)CoO2 and Na(1/3)CoO2(H2O)(4/3). Comparing the charge density of CoO2 and
      the Na doped phases indicates that doping does not simply add electrons to the
      t(2g) states. In fact, the electron added in the t(2g) state is dressed by hole
      density in the e(g) state and electron density in the oxygen states via
      rehybridization. In order to fully understand this phenomenon, a simple extension
      of the Hubbard Hamiltonian is proposed and solved using the dynamical mean-field
      theory. This model confirms that the rehybridization is driven by a competition
      between the on-site Coulomb interaction and the hybridization, and results in an
      effective screening of the low-energy excitations. Finally, we show that
      hydration causes the electronic structure to become more two dimensional.

PMID- 15169428
TI  - Efficiency of exciton and charge carrier photogeneration in a semiconducting
      polymer.
AB  - We determine the efficiencies for the formation of excitons and charge carriers
      following ultrafast photoexcitation of a semiconducting polymer (MEH-PPV). The
      simultaneous, quantitative determination of exciton and charge photoyields is
      achieved through subpicosecond studies of both the real and the imaginary
      components of the complex conductivity over a wide frequency range. Predominantly
      excitons, with near-unity quantum efficiency, are generated on excitation, while
      only a very small fraction (<10(-2)) of free charges are initially excited,
      consistent with rapid ( approximately 100 fs) hot exciton dissociation. These
      initial charges are very short lived, decaying on subpicosecond time scales.

PMID- 15169429
TI  - Quantum control of electron-phonon scatterings in artificial atoms.
AB  - The phonon-induced dephasing dynamics in optically excited semiconductor quantum
      dots is studied within the frameworks of the independent boson model and optimal
      control. We show that appropriate tailoring of laser pulses allow complete
      control of the optical excitation despite the phonon dephasing, a finding in
      marked contrast to other environment couplings.

PMID- 15169430
TI  - Resonant crossover of terahertz loss to the gain of a Bloch oscillating InAs/AlSb
      superlattice.
AB  - Terahertz absorption in waveguides loaded with InAs/AlSb super-superlattice mesas
      reveals a frequency dependent crossover from loss to gain that is related to the
      Stark ladder produced by an applied dc electric field. Electric field domains
      appear to be suppressed in the super-superlattice composed of many very short
      segments of superlattice, interrupted by heavily doped InAs regions. Resonant
      crossover is indicated by an increase in terahertz transmission as the Stark
      splitting or Bloch frequency determined by the applied dc electric field exceeds
      the measurement frequency.

PMID- 15169431
TI  - Magnetic Bloch oscillations in nanowire superlattice rings.
AB  - The recent growth of semiconductor nanowire superlattices encourages hope that
      Bloch-like oscillations in such structures formed into rings may soon be observed
      in the presence of a time-dependent magnetic flux threading the ring. These
      magnetic Bloch oscillations are a consequence of Faraday's law; the time
      dependent flux produces an electromotive force around the ring, thus leading to
      the Bloch-like oscillations. In the spectroscopic domain, generalized Wannier
      Stark states are found that are manifestations of the emf-induced localization of
      the states.

PMID- 15169432
TI  - Coulomb blockade of a noisy metallic box: a realization of Bose-Fermi Kondo
      models.
AB  - We focus on a metallic quantum dot coupled to a reservoir of electrons through a
      single-mode point contact and capacitively connected to a back gate, by including
      that the gate voltage can exhibit noise; this will occur when connecting the gate
      lead to a transmission line with a finite impedance. The voltage fluctuations at
      the back gate can be described through a Caldeira-Leggett model of harmonic
      oscillators. For weak tunneling between the lead and the dot, exploiting the
      anisotropic Bose-Fermi spin model, we show that zero-point fluctuations of the
      environment can markedly alter the Matveev Kondo fixed point leading to an
      amplification of the charge quantization phenomenon.

PMID- 15169433
TI  - Localization of surface states in disordered step lattices.
AB  - The character of the surface state wave function on regularly stepped Cu(111) is
      reinvestigated. It is shown that the qualitative change at terrace lengths around
      17 A observed previously by Ortega et al. [Phys. Rev. Lett. 84, 6110 (2000)]]
      must necessarily be described as a change from a propagating superlattice state
      to a terrace-confined quasi-one-dimensional state. This reconciles previous,
      apparently contradictory experimental results and sheds new light on the behavior
      of nearly free electrons in nanostructures. Possible mechanisms driving the
      localization are discussed on the basis of the surface state bulk penetration
      depth, which has been measured in both regimes.

PMID- 15169434
TI  - Microscopic origin of the next-generation fractional quantum Hall effect.
AB  - Most of the fractions observed to date belong to the sequences nu=n/(2pn+/-1) and
      nu=1-n/(2pn+/-1), n and p integers, understood as the familiar integral quantum
      Hall effect of composite fermions. These sequences fail to accommodate, however,
      many fractions such as nu=4/11 and 5/13, discovered recently in ultrahigh
      mobility samples at very low temperatures. We show that these "next generation"
      fractional quantum Hall states are accurately described as the fractional quantum
      Hall effect of composite fermions.

PMID- 15169435
TI  - Andreev reflection eigenvalue density in mesoscopic conductors.
AB  - The energy-dependent Andreev reflection eigenvalues determine the transport
      properties of normal-superconducting systems. We evaluate the eigenvalue density
      to get insight into the formation of resonant electron-hole transport channels.
      The circuit-theory-like method developed can be applied to any generic mesoscopic
      conductor or combinations thereof. We present the results for experimentally
      relevant cases of a diffusive wire and a double tunnel junction.

PMID- 15169436
TI  - Evolution of the Hall coefficient and the peculiar electronic structure of the
      cuprate superconductors.
AB  - Although the Hall coefficient R(H) is an informative transport property of metals
      and semiconductors, its meaning in the cuprate superconductors has been ambiguous
      because of its unusual characteristics. Here we show that a systematic study of
      R(H) in La2-xSrxCuO4 single crystals over a wide doping range establishes a
      qualitative understanding of its peculiar evolution, which turns out to reflect a
      two-component nature of the electronic structure caused by an unusual development
      of the Fermi surface recently uncovered by photoemission experiments.

PMID- 15169437
TI  - de Haas-van Alphen effect in ZrZn2 under pressure: crossover between two magnetic
      states.
AB  - We report measurements of the de Haas-van Alphen effect in ZrZn2 under
      hydrostatic pressures up to 21 kbar where the Curie temperature vanishes. The
      exchange splitting of a Fermi surface changes in behavior with increasing
      magnetic field, which is qualitatively consistent with the behavior of the high
      field magnetization, suggesting the existence of a crossover between two distinct
      magnetic states. These and previously unexplained findings may be understood in
      terms of a p-T-B phase diagram qualitatively similar to that of the ferromagnetic
      superconductor UGe2.

PMID- 15169438
TI  - Vortex fluctuations in the critical Casimir effect of superfluid and
      superconducting films.
AB  - Vortex-loop renormalization techniques are used to calculate the magnitude of the
      critical Casimir forces in superfluid films. The force is found to become
      appreciable when the size of the thermal vortex loops is comparable to the film
      thickness, and the results for T<T(c) are found to match very well with
      perturbative renormalization theories that have been carried out only for T>T(c).
      When applied to a high-T(c) superconducting film connected to a bulk sample, the
      Casimir force causes a voltage difference to appear between the film and the
      bulk, and estimates show that this may be readily measurable.

PMID- 15169439
TI  - Kohn anomaly in MgB2 by inelastic X-ray scattering.
AB  - We study phonons in MgB2 using inelastic x-ray scattering (1.6 and 6 meV
      resolution). We clearly observe the softening and broadening of the crucial E(2g)
      mode through the Kohn anomaly along GammaM, in excellent agreement with ab initio
      calculations. Low temperature measurements (just above and below T(c)) show
      negligible changes for the momentum transfers investigated and no change in the
      E(2g) mode at A between room temperature and 16 K. We report the presence of a
      longitudinal mode along GammaA near in energy to the E(2g) mode that is not
      predicted by theory.

PMID- 15169440
TI  - Softening of Cu-O bond stretching phonons in tetragonal HgBa2CuO4+delta.
AB  - Phonons in nearly optimally doped HgBa(2)CuO(4+delta) were studied by inelastic x
      ray scattering. The dispersion of the low-energy modes is well described by a
      shell model, while the Cu-O bond stretching mode at high energy shows strong
      softening towards the zone boundary, which deviates strongly from the model. This
      seems to be common in the hole-doped high-T(c) superconducting cuprates, and,
      based on this work, not related to a lattice distortion specific to each
      material.

PMID- 15169441
TI  - Ferromagnetic in-plane spin fluctuations in NaxCoO2 observed by neutron inelastic
      scattering.
AB  - We present neutron scattering spectra taken from a single crystal of Na0.75CoO2,
      the precursor to a novel cobalt-oxide superconductor. The data contain a
      prominent inelastic signal at low energies ( approximately 10 meV), which is
      localized in wave vector about the origin of two-dimensional reciprocal space.
      The signal is highly dispersive, and decreases in intensity with increasing
      temperature. We interpret these observations as direct evidence for the existence
      of ferromagnetic spin fluctuations within the cobalt-oxygen layers.

PMID- 15169442
TI  - Magnetoelastic instability in molecular antiferromagnetic rings.
AB  - Lattice stability in a model of an antiferromagnetic ring coupled to adiabatic
      phonons is investigated for different values of the spin and numbers of magnetic
      sites. The magnetoelastic transition is shown to be heavily affected by the spin
      value, displaying a qualitative difference in the nature of the instability for
      spin one-half. Among the different synthesized materials, Cu8 seems to be the
      best candidate to observe lattice dimerization in these systems. Our analysis
      excludes stable lattice distortions in higher spin rings. The effects of thermal
      fluctuations are studied in the Cu8 model, where a characteristic crossover
      temperature is estimated.

PMID- 15169443
TI  - Origin of magnetic and magnetoelastic tweedlike precursor modulations in ferroic
      materials.
AB  - Based on experimental observations of modulated magnetic patterns in a
      Co0.5Ni0.205Ga0.295 alloy, we propose a model to describe a (purely) magnetic
      tweed and a magnetoelastic tweed. The former arises above the Curie (or Neel)
      temperature due to magnetic disorder. The latter results from compositional
      fluctuations coupling to strain and then to magnetism through the magnetoelastic
      interaction above the structural transition temperature. We discuss the origin of
      purely magnetic and magnetoelastic precursor modulations and their experimental
      thermodynamic signatures.

PMID- 15169444
TI  - Observation of an amplitude collapse and revival of chirped coherent phonons in
      bismuth.
AB  - We have studied the A(1g) coherent phonons in bismuth generated by high fluence
      ultrashort laser pulses. We observed that the nonlinear regime, where the
      phonons' oscillation parameters depend on fluence, consists of subregimes with
      distinct dynamics. Just after entering the nonlinear regime, the phonons become
      chirped. Increasing the fluence further leads to the emergence of a collapse and
      revival, which next turns into multiple collapses and revivals. This is explained
      by the dynamics of a wave packet in an anharmonic potential, where the packet
      periodically breaks up and reconstitutes in its original form, giving convincing
      evidence that the phonons are in a quantum state, with no classical analog.

PMID- 15169445
TI  - Surface plasmon dynamics of simple metal clusters excited with femtosecond
      optical pulses.
AB  - We report a new mechanism on the dynamics of correlated electrons in simple metal
      clusters which manifests by a strong electron temperature dependence of the
      surface plasmon resonance spectral profile. This effect is revealed thanks to a
      theoretical approach based on the time-dependent local-density approximation at
      finite electronic temperature, and it should be experimentally observable using
      pump-probe femtosecond spectroscopy techniques.

PMID- 15169446
TI  - Complete conditions for entanglement transfer.
AB  - We investigate the conditions to entangle two qubits interacting with local
      environments driven by a continuous-variable correlated field. We find the
      conditions to transfer the entanglement from the driving field to the qubits both
      in dynamical and steady-state cases. We see how the quantum correlations
      initially present in the driving field play a critical role in the entanglement
      transfer process. The system we treat is general enough to be adapted to
      different physical setups.

PMID- 15169447
TI  - Self-sustained activity in a small-world network of excitable neurons.
AB  - We study the dynamics of excitable integrate-and-fire neurons in a small-world
      network. At low densities p of directed random connections, a localized transient
      stimulus results either in self-sustained persistent activity or in a brief
      transient followed by failure. Averages over the quenched ensemble reveal that
      the probability of failure changes from 0 to 1 over a narrow range in p; this
      failure transition can be described analytically through an extension of an
      existing mean-field result. Exceedingly long transients emerge at higher
      densities p; their activity patterns are disordered, in contrast to the mostly
      periodic persistent patterns observed at low p. The times at which such patterns
      die out follow a stretched-exponential distribution, which depends sensitively on
      the propagation velocity of the excitation.

PMID- 15169448
TI  - Single molecule diffraction.
AB  - For solving the atomic structure of organic molecules such as small proteins
      which are difficult to crystallize, the use of a jet of doped liquid helium
      droplets traversing a continuous high energy electron beam is proposed as a means
      of obtaining electron diffraction patterns (serial crystallography). Organic
      molecules (such as small proteins) within the droplet (and within a vitreous ice
      jacket) may be aligned by use of a polarized laser beam. Iterative methods for
      solving the phase problem are indicated. Comparisons with a related plan for
      pulsed x-ray diffraction from single proteins in a molecular beam are provided.

PMID- 15169449
TI  - Regular and alternant spiral waves of contractile motion on rat ventricle cell
      cultures.
AB  - We demonstrate that meandering as well as regular spiral waves can form in a well
      controlled culture layer of rat ventricle cells and that the meandering spiral
      wave, in particular, can generate an alternant rhythm. These observations are
      made possible by a newly developed, noninvasive phase contrast macro-optics that
      is simple but highly effective in visualizing the contractile motion of the
      populations of cardiac cells.

PMID- 15169450
TI  - Optical microrheology using rotating laser-trapped particles.
AB  - We demonstrate an optical system that can apply and accurately measure the torque
      exerted by the trapping beam on a rotating birefringent probe particle. This
      allows the viscosity and surface effects within liquid media to be measured
      quantitatively on a micron-size scale using a trapped rotating spherical probe
      particle. We use the system to measure the viscosity inside a prototype cellular
      structure.

PMID- 15169451
TI  - Self-regulated complexity in cultured neuronal networks.
AB  - New quantified observables of complexity are identified and utilized to study
      sequences (time series) recorded during the spontaneous activity of different
      size cultured networks. The sequence is mapped into a tiled time-frequency domain
      that maximizes the information about local time-frequency resolutions. The
      sequence regularity is associated with the domain homogeneity and its complexity
      with its local and global variations. Shuffling the recorded sequence lowers its
      complexity down to artificially constructed ones. The new observables are
      utilized to identify self-regulation motifs in observed complex network activity.

PMID- 15169452
TI  - Mathematical analysis and simulations of the neural circuit for locomotion in
      lampreys.
AB  - We analyze the dynamics of the neural circuit of the lamprey central pattern
      generator. This analysis provides insight into how neural interactions form
      oscillators and enable spontaneous oscillations in a network of damped
      oscillators, which were not apparent in previous simulations or abstract phase
      oscillator models. We also show how the different behavior regimes (characterized
      by phase and amplitude relationships between oscillators) of forward or backward
      swimming, and turning, can be controlled using the neural connection strengths
      and external inputs.

PMID- 15169453
TI  - Charge inversion and flow reversal in a nanochannel electro-osmotic flow.
AB  - Ion distribution and velocity profiles for electro-osmotic flow in a 3.49 nm wide
      slit channel with a surface charge density of -0.285 C/m(2) are studied using
      molecular dynamics simulations. Simulation results indicate that the
      concentration of the co-ion exceeds that of the counterion in the region 0.53 nm
      away from the channel wall, and the electro-osmotic flow is in the opposite
      direction to that predicted by the classical continuum theory. The charge
      inversion is mainly caused by the molecular nature of water and ions. The flow
      reversal is caused by the immobilization of counterions adsorbed on the channel
      wall and due to the charge inversion phenomena.

PMID- 15169454
TI  - Slip and flow in soft particle pastes.
AB  - Concentrated dispersions of soft particles are shown to exhibit a generic slip
      behavior near smooth surfaces. Slip results from a balance between osmotic forces
      and noncontact elastohydrodynamic interaction between the squeezed particles and
      the wall. A model is presented that predicts the slip properties and provides
      insight into the behavior of the bulk paste.

PMID- 15169455
TI  - Stable squares and other oscillatory turing patterns in a reaction-diffusion
      model.
AB  - We study the Brusselator reaction-diffusion model under conditions where the Hopf
      mode is supercritical and the Turing band is subcritical. Oscillating Turing
      patterns arise in the system when bulk oscillations lose their stability to
      spatial perturbations. Spatially uniform external periodic forcing can generate
      oscillating Turing patterns when both the Turing and Hopf modes are subcritical
      in the autonomous system. Most of the symmetric patterns show period doubling in
      both space and time. Patterns observed include squares, rhombi, stripes, and
      hexagons.

PMID- 15169457
TI  - Promoter-induced reactive phase separation in surface reactions.
AB  - Promoters are adsorbed mobile species which do not directly participate in a
      catalytic surface reaction, but can influence its rate. Often, they are
      characterized by strong attractive interactions with one of the reactants. We
      show that these conditions lead to a Turing instability of the uniform state and
      to the formation of reaction-induced periodic concentration patterns.
      Experimentally such patterns are observed in catalytic water formation on a
      Rh(110) surface in the presence of coadsorbed potassium.

PMID- 15169458
TI  - Helium diffusion through H2O and D2O amorphous ice: observation of a lattice
      inverse isotope effect.
AB  - The diffusion of He through both H2O and D2O amorphous solid water (ASW) has been
      measured between 55 and 110 K. We find the diffusion rate is dependent on the
      isotopic composition of the ASW lattice. This lattice isotope effect is the
      "inverse" of a normal isotope effect in that diffusion is faster in the heavier
      (D2O) isotope. Transition state theory calculations show that the inverse isotope
      effect is due to a tight transition state and predominantly arises from the zero
      point vibrational energy associated with the frustrated rotational modes of water
      in the lattice.

PMID- 15169456
TI  - Molecular mechanism of Peptide-induced pores in membranes.
AB  - We suggest a physical mechanism by which antimicrobial peptides spontaneously
      induce stable pores in membranes. Peptide binding to a lipid bilayer causes an
      internal stress, or internal membrane tension, that can be sufficiently strong to
      create pores. Like detergents, peptides have a high affinity for the rim of the
      pore. Binding to the rims reduces the line tension and decreases the number of
      peptides causing the internal membrane tension. Consequently, the pore radius is
      stable. The pore formation resembles a phase transition.

PMID- 15169459
TI  - Network structures from selection principles.
AB  - We present an analysis of the topologies of a class of networks which are optimal
      in terms of the requirements of having as short a route as possible between any
      two nodes while yet keeping the congestion in the network as low as possible.
      Strikingly, we find a variety of distinct topologies and novel phase transitions
      between them on varying the number of links per node. Our results suggest that
      the emergence of the topologies observed in nature may arise both from growth
      mechanisms and the interplay of dynamical mechanisms with a selection process.

PMID- 15169460
TI  - Comment on "Millennium scale sunspot number reconstruction: evidence for an
      unusually active sun since the 1940s".

PMID- 15169462
TI  - Comment on "Exact self-similar solutions of the generalized nonlinear Schrodinger
      equation with distributed coefficients".

PMID- 15169464
TI  - Comment on "Gapless spin-1 neutral collective mode branch for graphite".

PMID- 15169466
TI  - Comment on "Absence of compressible edge channel rings in quantum antidots".

PMID- 15169468
TI  - Comment on "Coexistence of superconductivity and ferromagnetism in ferromagnetic
      metals".

PMID- 15169470
TI  - Comment on "Monitoring the transitions of the charge-induced reconstruction of
      Au(110) by reflection anisotropy spectroscopy".

PMID- 15169471
TI  - Experimental demonstration of single photon nonlocality.
AB  - In this Letter we experimentally implement a single photon Bell test based on the
      ideas of S. Tan et al. [Phys. Rev. Lett. 66, 252 (1991)]] and L. Hardy [Phys.
      Rev. Lett. 73, 2279 (1994)]]. A double homodyne measurement is used to measure
      correlations in the Fock space spanned by zero and one photons. Local oscillators
      used in the correlation measurement are distributed to two observers by
      copropagating it in an orthogonal polarization mode. This method eliminates the
      need for interferometrical stability in the setup, consequently making it a
      robust and scalable method.

PMID- 15169472
TI  - Dissociation and decay of ultracold sodium molecules.
AB  - The dissociation of ultracold molecules was studied by ramping an external
      magnetic field through a Feshbach resonance. The observed dissociation energies
      directly yielded the strength of the atom-molecule coupling. They showed
      nonlinear dependence on the ramp speed. This was explained by a Wigner threshold
      law which predicts that the decay rate of the molecules above threshold increases
      with the density of states. In addition, inelastic molecule-molecule and molecule
      atom collisions were characterized.

PMID- 15169473
TI  - Stability of macroscopic entanglement under decoherence.
AB  - We investigate the lifetime of macroscopic entanglement under the influence of
      decoherence. For Greenberger-Horne-Zeilinger-type superposition states, we find
      that the lifetime decreases with the size of the system (i.e., the number of
      independent degrees of freedom), and the effective number of subsystems that
      remain entangled decreases with time. For a class of other states (e.g., cluster
      states), however, we show that the lifetime of entanglement is independent of the
      size of the system.

PMID- 15169474
TI  - Coherent matter-wave manipulation in the diabatic limit.
AB  - Guided systems for coherent matter waves are expected to offer substantial
      improvements over unguided systems, but adiabatic coupler proposals have proven
      difficult to realize. We outline instead considerations for a coherence
      preserving diabatic approach enabling filters, couplers, and interferometers that
      can accept multimode guide inputs of up to magneto-optical-trap temperatures.

PMID- 15169475
TI  - Localization of two-component Bose-Einstein condensates in optical lattices.
AB  - We study nonlinear localization of a two-component Bose-Einstein condensate (BEC)
      in a one-dimensional optical lattice. Our theory shows that spin-dependent
      optical lattices can be used to effectively manipulate the nonlinear interactions
      between the BEC components, and to observe composite localized states of a BEC in
      both bands and gaps of the matter-wave spectrum.

PMID- 15169476
TI  - Current fluctuations in nonequilibrium diffusive systems: an additivity
      principle.
AB  - We formulate a simple additivity principle allowing one to calculate the whole
      distribution of current fluctuations through a large one dimensional system in
      contact with two reservoirs at unequal densities from the knowledge of its first
      two cumulants. This distribution (which in general is non-Gaussian) satisfies the
      Gallavotti-Cohen symmetry and generalizes the one predicted recently for the
      symmetric simple exclusion process. The additivity principle can be used to study
      more complex diffusive networks including loops.

PMID- 15169477
TI  - Controlling the motion of magnetic flux quanta.
AB  - We study the transport of vortices in superconductors with triangular arrays of
      boomerang- or V-shaped asymmetric pinning wells, when applying an alternating
      electrical current. The asymmetry of the pinning landscape induces a very
      efficient "diode" effect, that allows the sculpting at will of the magnetic field
      profile inside the sample. We present the first quantitative study of magnetic
      "lensing" of fluxons inside superconductors. Our proposed vortex lens provides a
      near threefold increase of the vortex density at its "focus" regions. The main
      numerical features have been derived analytically.

PMID- 15169478
TI  - Particle acceleration in relativistic current sheets.
AB  - Relativistic current sheets have been proposed as the sites of dissipation in
      pulsar winds, jets in active galaxies, and other Poynting flux dominated flows.
      It is shown that the steady versions of these structures differ from their
      nonrelativistic counterparts because they do not permit transformation to a de
      Hofmann-Teller frame with zero electric field. Instead, their generic form is
      that of a true neutral sheet with no linking magnetic field component normal to
      the sheet. The maximum energy to which such structures can accelerate particles
      is derived, and used to compute the maximum frequency of the subsequent
      synchrotron radiation. This can be substantially in excess of standard estimates.
      In the magnetically driven gamma-ray burst scenario, acceleration of electrons is
      possible to energies sufficient to enable photon-photon pair production after an
      inverse Compton scattering event.

PMID- 15169479
TI  - Skewness as a test of the equivalence principle.
AB  - The skewness of the large-scale distribution of matter has long been known to be
      a probe of gravitational clustering. Here we show that the skewness is also a
      probe of violation of the equivalence principle between dark matter and baryons.
      The predicted level of violation can be tested with the forthcoming data from the
      Sloan Digital Sky Survey.

PMID- 15169481
TI  - Topology and H-flux of T-dual manifolds.
AB  - We present a general formula for the topology and H-flux of the T-dual of a type
      II compactification. Our results apply to T-dualities with respect to any free
      circle action. In particular, we find that the manifolds on each side of the
      duality are circle bundles whose curvatures are given by the integral of the dual
      H-flux over the dual circle. As a corollary we conjecture an obstruction to
      multiple T-dualities, generalizing the obstruction known to exist on the twisted
      torus. Examples include SU(2) Wess-Zumino-Witten models, lens spaces, and the
      supersymmetric string theory on the nonspin AdS5 x CP2 x S1 compactification.

PMID- 15169480
TI  - Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino
      Observatory with enhanced neutral current sensitivity.
AB  - The Sudbury Neutrino Observatory has precisely determined the total active
      (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of
      the nu(e) survival probability. The measurements were made with dissolved NaCl in
      heavy water to enhance the sensitivity and signature for neutral-current
      interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6)
      cm(-2) s(-1), in agreement with previous measurements and standard solar models.
      A global analysis of these and other solar and reactor neutrino results yields
      Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees.
      Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

PMID- 15169482
TI  - Observation of parity nonconservation in moller scattering.
AB  - We report a measurement of the parity-violating asymmetry in fixed target
      electron-electron (Moller) scattering: A(PV)=[-175+/-30(stat)+/-20(syst)] x 10(
      9). This first direct observation of parity nonconservation in Moller scattering
      leads to a measurement of the electron's weak charge at low energy Q(e)(W)=
      0.053+/-0.011. This is consistent with the standard model expectation at the
      current level of precision: sin((2)theta(W)(M(Z))((-)MS)=0.2293+/-0.0024(stat)+/
      0.0016(syst)+/-0.0006(theory).

PMID- 15169484
TI  - Proposed search for a(0)(0)(980)-f(0)(980) mixing in polarization phenomena.
AB  - The K+ and K0 meson mass difference induces the mixing of the a(0)(0)(980) and
      f(0)(980) resonances, the amplitude of which, between the K+K- and K0(-)K(0)
      thresholds, is large in magnitude, of the order of m(K)m(2)(K0)sqrt[-m(2)(K+)]
      approximately sqrt[alpha] m(2)(K), and possesses the phase sharply varying by
      about 90 degrees. We suggest performing the polarized target experiments on the
      reaction pi(-)p-->etapi(0)n at high energy in which the fact of the existence of
      a(0)(0)(980)-f(0)(980) mixing can be unambiguously and very easily established
      through the presence of a strong jump in the azimuthal asymmetry of the etapi(0)
      S wave production cross section near the K(-)K thresholds. The presented
      estimates of the polarization effect to be expected in experiment are to a great
      extent model independent.

PMID- 15169486
TI  - Confinement versus chiral symmetry.
AB  - We construct an effective Lagrangian which illustrates why color deconfines when
      chiral symmetry is restored in hot gauge theories with quarks in the fundamental
      representation. For quarks in the adjoint representation we show that, while
      deconfinement and the chiral transition do not need to coincide, entanglement
      between them is still present. Extension to the chemical potential driven
      transition is discussed.

PMID- 15169487
TI  - Enhancement of phase space density by increasing trap anisotropy in a magneto
      optical trap with a large number of atoms.
AB  - The phase space density of dense, cylindrical clouds of atoms in a 2D magneto
      optic trap is investigated. For a large number of trapped atoms (>10(8)), the
      density of a spherical cloud is limited by photon reabsorption. However, as the
      atom cloud is deformed to reduce the radial optical density, the temperature of
      the atoms decreases due to the suppression of multiple scattering leading to an
      increase in the phase space density. A density of 2 x 10(-4) has been achieved in
      a magneto-optic trap containing 2 x 10(8) atoms.

PMID- 15169488
TI  - Quantum and thermal fluctuation effects on the photoabsorption spectra of
      clusters.
AB  - A first principles approach for the calculation of photoabsorption cross sections
      of clusters and molecules is presented which includes both quantum and thermal
      fluctuations. The method relies on an ab initio path integral representation of
      the nuclear quantum motion in conjunction with time-dependent density-functional
      theory for electronic excitations. It is shown that quantum fluctuations of cold
      lithium clusters, such as Li8 below 50 K, affect significantly their
      photoabsorption spectra.

PMID- 15169489
TI  - Strong influence of hole shape on extraordinary transmission through periodic
      arrays of subwavelength holes.
AB  - We show that extraordinary light transmission of periodic subwavelength hole
      arrays, generally attributed to surface-plasmon resonances, is strongly
      influenced by the hole shape. Both experiments and calculations, based on a
      Fourier modal method, demonstrate that a shape change from circular to
      rectangular increases the normalized transmission by an order of magnitude while
      the hole area decreases. Moreover, the spectra exhibit large redshifts
      (approximately 2500 cm(-1)). A comparison with the transmission of isolated holes
      shows that shape resonances of the rectangular holes play a dominant role.

PMID- 15169490
TI  - Spontaneous ratchet effect in a granular gas.
AB  - The spontaneous clustering of a vibrofluidized granular gas is employed to
      generate directed transport in two different compartmentalized systems: a
      granular fountain in which the transport takes the form of convection rolls, and
      a granular ratchet with a spontaneous particle current perpendicular to the
      direction of energy input. In both instances, transport is not due to any system
      intrinsic anisotropy, but arises as a spontaneous collective symmetry breaking
      effect of many interacting granular particles. The experimental and numerical
      results are quantitatively accounted for within a flux model.

PMID- 15169491
TI  - Persistent holes in a fluid.
AB  - We observe stable holes in a vertically oscillated 0.5 cm deep aqueous suspension
      of cornstarch. Holes appear only if a finite perturbation is applied to the layer
      for accelerations a above 10g. Holes are circular and approximately 0.5 cm wide,
      and can persist for more than 10(6) cycles. Above a approximately equal to 17g
      the rim of the hole becomes unstable, producing fingerlike protrusions or hole
      division. At higher acceleration, the hole delocalizes, growing to cover the
      entire surface with erratic undulations. We find similar behavior in an aqueous
      suspension of glass microspheres.

PMID- 15169492
TI  - Harmonic emission from the rear side of thin overdense foils irradiated with
      intense ultrashort laser pulses.
AB  - The harmonic emission from thin solid carbon and aluminum foils, irradiated by
      150 fs long frequency-doubled Ti:sapphire laser pulses at lambda=395 nm and peak
      intensities of a few 10(18) W/cm(2), has been studied. In addition to the
      harmonics emitted from the front side in the specular direction, we observe
      harmonics up to the 10th order, including the fundamental from the rear side in
      the direction of the incident beam, while the foil is still strongly overdense.
      The experimental observations are well reproduced by particle-in-cell
      simulations. They reveal that strong coupling between the laser-irradiated side
      and the rear side occurs via the nonlocal electron current driven by the laser
      light.

PMID- 15169494
TI  - Influence of asymmetric energetic ion distributions on sawtooth stabilization.
AB  - The effect of energetic asymmetrically distributed ions on the stability of the
      internal kink mode in tokamaks is analyzed. Circulating ions which intersect the
      resonant surface due to finite radial excursion contribute to the mode either in
      the region of favorable or unfavorable curvature depending on the sign of v(
      parallel ). Internal kink mode stabilization for predominantly cocirculating ion
      populations is consistent with the observation of long sawteeth using tangential
      coinjection of neutral beams in JT-60U [Nucl. Fusion 40, 1383 (2000)]]. Off-axis
      neutral beam heating emerges as a possible means of assisting sawtooth control in
      future fusion grade experiments.

PMID- 15169493
TI  - Dependence of shell mix on feedthrough in direct drive inertial confinement
      fusion.
AB  - The mixing of cold, high-density shell plasma with the low-density, hot spot
      plasma by the Rayleigh-Taylor instability in inertial confinement fusion is
      experimentally shown to correlate with the calculated perturbation feedthrough
      from the ablation surface to the inner shell surface. A fourfold decrease in the
      density of shell material in the mix region of direct drive implosions of gas
      filled spherical plastic shells having predicted convergence ratios approximately
      15 was observed when laser imprint levels were reduced and the initial shell was
      thicker, corresponding to a reduction in the feedthrough rms level by a factor of
      6. Shell mix is also shown to limit the spherical compression of the implosion.

PMID- 15169495
TI  - Diffraction of neutral helium clusters: evidence for "magic numbers".
AB  - The size distributions of neutral 4He clusters in cryogenic jet beams, analyzed
      by diffraction from a 100 nm period transmission grating, reveal magic numbers at
      N=10-11, 14, 22, 26-27, and 44 atoms. Whereas magic numbers in nuclei and
      clusters are attributed to enhanced stabilities, this is not expected for quantum
      fluid He clusters on the basis of numerous calculations. These magic numbers
      occur at threshold sizes for which the quantized excitations calculated with the
      diffusion Monte Carlo method are stabilized, thereby providing the first
      experimental confirmation for the energy levels of 4He clusters.

PMID- 15169496
TI  - Direct observation of anisotropic interparticle forces in nematic colloids with
      optical tweezers.
AB  - Interparticle forces in a nematic liquid-crystal colloid have been directly
      observed by the dual beam laser trapping method with pN sensitivity. We introduce
      two different types of spatial distributions of forces, detected between the
      particles accompanied by hyperbolic hedgehog defects. These force distributions
      lead to specific particle arrangements, which are both stabilized by the balance
      of the orientational stress field of nematics. On the basis of these results, we
      propose novel artificial construction for multiparticle regular arrangements.

PMID- 15169498
TI  - Vibrational lifetimes and isotope effects of interstitial oxygen in silicon and
      germanium.
AB  - Decay dynamics of local vibrational modes provides unique information about
      energy relaxation processes to solid-state phonon bath. In this Letter the
      lifetimes of the asymmetric stretch mode of interstitial 16O and 17O isotopes in
      Si are measured at 10 K directly by time-resolved, transient bleaching
      spectroscopy to be 11.5 and 4.5 ps, respectively. A calculation of the three
      phonon density of states shows that the 17O mode lies in the highest phonon
      density resulting in the shortest lifetime. The lifetime of the 16O mode in Ge is
      measured to be 125 ps, i.e., approximately 10 times longer than in Si. The
      interaction between the local modes and the lattice vibrations is discussed
      according to the activity of phonon combinations.

PMID- 15169499
TI  - Spatial structures and dynamics of kinetically constrained models of glasses.
AB  - Kob and Andersen's simple lattice models for the dynamics of structural glasses
      are analyzed. Although the particles have only hard core interactions, the
      imposed constraint that they cannot move if surrounded by too many others causes
      slow dynamics. On Bethe lattices, a dynamical transition to a partially frozen
      phase occurs. In finite dimensions there exist rare mobile elements that destroy
      the transition. At low vacancy density v, the spacing Xi between mobile elements
      diverges exponentially or faster in 1/v. Within the mobile elements, the dynamics
      is intrinsically cooperative, and the characteristic time scale diverges faster
      than any power of 1/v (although slower than Xi). The tagged-particle diffusion
      coefficient vanishes roughly as Xi(-d).

PMID- 15169485
TI  - Multistrange baryon production in Au-Au collisions at sqrt[s(NN)]=130 GeV.
AB  - The transverse mass spectra and midrapidity yields for Xis and Omegas are
      presented. For the 10% most central collisions, the (-)Xi(+)/h(-) ratio increases
      from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies
      while the Xi(-)/h(-) stays approximately constant. A hydrodynamically inspired
      model fit to the Xi spectra, which assumes a thermalized source, seems to
      indicate that these multistrange particles experience a significant transverse
      flow effect, but are emitted when the system is hotter and the flow is smaller
      than values obtained from a combined fit to pi, K, p, and Lambdas.

PMID- 15169497
TI  - Four-well tunneling States and elastic response of clathrates.
AB  - We present resonant ultrasound elastic constant measurements of the Eu8Ga16Ge30
      and Sr8Ga16Ge30 clathrates. The elastic response of the Eu clathrate provides
      clear evidence for the existence of a new type of four-well tunneling states,
      described by two nearly degenerate four level systems (FLS). The FLS's are
      closely linked with the fourfold split positions of Eu known from neutron
      diffraction density profiles. Using a realistic potential we estimate the
      tunneling frequencies and show that the energy gap between the two FLS's explains
      the observed harmonic oscillator type specific heat. In addition the quadrupolar
      interaction of FLS's with elastic strains explains the pronounced depression
      observed in elastic constant measurements. In the case of the Sr clathrate, we
      explain the elastic properties assuming the same type of interaction, but with Sr
      Einstein mode.

PMID- 15169500
TI  - Concentrated point defects in and order-disorder transition temperature of
      intermetallic compounds.
AB  - In this Letter, a scheme that combines first-principles methods, statistical
      mechanics, and a self-consistent procedure is presented to evaluate the point
      defect concentrations in intermetallic compounds. The obtained point defect
      concentrations can be further used to predict the order-disorder transformation
      temperature.

PMID- 15169501
TI  - Jamming, two-fluid behavior, and "self-filtration" in concentrated particulate
      suspensions.
AB  - We study the flow of model hard-sphere colloidal suspensions at high volume
      fraction Phi driven through a constriction by a pressure gradient. Above a
      particle-size dependent limit Phi(0), direct microscopic observations demonstrate
      jamming and unjamming-conversion of fluid to solid and vice versa-during flow. We
      show that such a jamming flow produces a reduction in colloid concentration
      Phi(x) downstream of the constriction. We propose that this "self-filtration"
      effect is due to a combination of jamming of the particulate part of the system
      and continuing flow of the liquid part, i.e., the solvent, through the pores of
      the jammed solid. Thus we link jamming in colloidal and granular media with a
      "two-fluid-like" picture of the flow of concentrated suspensions. Results are
      also discussed in the light of the original experiments of Reynolds on dilation
      in granular materials.

PMID- 15169502
TI  - Atomic dynamics in liquids with competing interactions.
AB  - The influence of the type of atomic interaction on the atomic dynamics is studied
      for liquid Na(x)Sn(1-x) (x = 0.9, 0.77, 0.57, 0.5, 0.33) alloys by cold neutron
      inelastic scattering. The dispersions obtained from the longitudinal current
      correlation function J(l)(Q,omega) show clear evidence for the dependence of the
      dynamics on the type of interaction (metallic, ionic, partly covalent) tuned by
      changing the composition of the alloy. For the first time, a second dispersion
      branch is observed in the total J(l)(Q,omega) around Q(p), the position of the
      principal peak of S(Q), for the Sn-rich compositions. The dynamic properties are
      discussed and compared to results of recent ab initio molecular dynamics
      simulations.

PMID- 15169503
TI  - Surface-induced ordering of nematics in an external field: the strong influence
      of tilted walls.
AB  - Microscopic theory is used to investigate surface-induced order in a model
      nematic subjected to an external orienting field. The wall-particle interaction
      tends to orient particles perpendicular to the surface. It is shown that if the
      wall is tilted at approximately 45 degrees to the field, the reorientational
      effects can be an order of magnitude larger than those observed for perpendicular
      or parallel orientations. The surprising observation is associated with the
      breaking of a particular bulk symmetry. A possible practical application of the
      tilted geometry is briefly discussed.

PMID- 15169504
TI  - Phase diagram of random heteropolymers.
AB  - We propose a new analytic approach to study the phase diagram of random
      heteropolymers, based on the cavity method. For copolymers we analyze the nature
      and phenomenology of the glass transition as a function of sequence correlations.
      Depending on these correlations, we find that two different scenarios for the
      glass transition can occur. We show that, beside the much studied possibility of
      an abrupt freezing transition at low temperature, the system can exhibit, upon
      cooling, a first transition to a soft glass phase with fully broken replica
      symmetry and a continuously growing degree of freezing as the temperature is
      lowered.

PMID- 15169505
TI  - Structure of liquid iron at pressures up to 58 GPa.
AB  - We report structural data on liquid iron at pressures up to 58 GPa measured by x
      ray scattering in a laser heated diamond anvil cell. The determined structure
      factor preserves essentially the same shape along the melting curve. Our data
      demonstrate that liquid iron at high pressures is a close-packed hard-sphere
      liquid. The results place important constraints on the thermodynamic and
      transport properties of liquid iron and the melting curve of iron.

PMID- 15169506
TI  - Density-functional calculations of alpha, beta, gamma, delta, delta', and epsilon
      plutonium.
AB  - Total energies for the six known polymorphs of plutonium metal have been
      calculated within spin and orbital polarized density-functional theory as a
      function of lattice constant. Theoretical equilibrium volumes and bulk moduli
      correspond well with experimental data and the calculated total energies are
      consistent with the known phase diagram of Pu. It is shown that a preference for
      the formation of magnetic moments, increasing through the alpha-->beta-->gamma
      phases, explains their position in the ambient pressure phase diagram and their
      anomalous variation of atomic density. A simple model is presented that
      establishes a relationship between atomic density, crystal symmetry, and magnetic
      moments which is universally valid for all Pu phases.

PMID- 15169508
TI  - Breakdown of dynamic scaling in thin film binary liquids undergoing phase
      separation.
AB  - The kinetics of phase separation in thin polymer blend films displaying discrete
      and bicontinuous domain morphologies are examined. For discrete domains, the
      correlation length xi grows as t(1/3), in agreement with a coalescence model. By
      plotting xi/d vs t/t(i) (initiation time), universal growth behavior is obtained
      for thickness values (d) from 1000 to 190 nm. In contrast, bicontinuous domains
      grow with a decreasing exponent, 0.62 to 0.28, as d decreases from 900 to 90 nm
      (i.e., no universal growth). This slowing down with reduced dimensionality
      suggests suppression of lateral hydrodynamic pumping.

PMID- 15169483
TI  - Limits on the decay-rate difference of neutral B mesons and on CP, T, and CPT
      violation in B(0-0)B oscillations.
AB  - Using events in which one of two neutral B mesons from the decay of an
      Upsilon(4S) meson is fully reconstructed, we determine parameters governing decay
      (DeltaGamma(d)/Gamma(d)), CP, and T violation (|q/p|), and CP and CPT violation
      (Re z,Im z). The results, obtained from an analysis of 88 x 10(6) Upsilon(4S)
      decays recorded by BABAR, are sgn(Re lambda(CP))DeltaGamma(d)/Gamma(d)=-0.008+/
      0.037(stat)+/-0.018(syst)[-0.084,0.068],|q/p|=1.029+/-0.013(stat)+/
      0.011(syst)[1.001,1.057],(Re lambda(CP)/|lambda(CP)|) Re z=0.014+/-0.035(stat)+/
      0.034(syst)[-0.072,0.101],Im z=0.038+/-0.029(stat)+/-0.025(syst)[-0.028,0.104].
      The values inside the square brackets indicate the 90% confidence-level
      intervals. These results are consistent with standard model expectations.

PMID- 15169509
TI  - Dynamic criticality in glass-forming liquids.
AB  - We propose that the dynamics of supercooled liquids and the formation of glasses
      can be understood from the existence of a zero-temperature dynamical critical
      point. To support our proposal, we derive a dynamic field theory for a generic
      kinetically constrained model, which we expect to describe the dynamics of a
      supercooled liquid. We study this field theory using the renormalization group
      (RG). Its long time behavior is dominated by a zero-temperature critical point,
      which for d>2 belongs to the directed percolation universality class. Molecular
      dynamics simulations seem to confirm the existence of dynamic scaling behavior
      consistent with the RG predictions.

PMID- 15169507
TI  - Discretization dependence of criticality in model fluids: a hard-core
      electrolyte.
AB  - Grand-canonical simulations at various levels, zeta=5-20, of fine-lattice
      discretization are reported for the near-critical 1:1 hard-core electrolyte or
      restricted primitive model (RPM). With the aid of finite-size scaling analyses,
      it is shown convincingly that, contrary to recent suggestions, the universal
      critical behavior is independent of zeta (> or approximately 4), thus the
      continuum (zeta--> infinity ) RPM exhibits Ising-type (as against classical, self
      avoiding walk, XY, etc.) criticality. A general consideration of lattice
      discretization provides effective extrapolation of the intrinsically erratic zeta
      dependence, yielding (T*(c),rho*(c)) approximately equal to (0.0493(3),0.075) for
      the zeta=infinity RPM.

PMID- 15169510
TI  - Strain, size, and composition of InAs quantum sticks embedded in InP determined
      via grazing incidence x-ray anomalous diffraction.
AB  - We have used x-ray anomalous diffraction to recover the model-independent Fourier
      transform (x-ray structure factor) of InAs quantum sticklike islands embedded in
      InP. The average height of the quantum sticks, as deduced from the width of the
      structure factor profile, is 2.54 nm. The InAs out-of-plane deformation, relative
      to InP, is 6.1%. Diffraction anomalous fine structure provides evidence of pure
      InAs quantum sticks. Finite difference method calculations reproduce well the
      diffraction data, and give the strain along the growth direction. The chemical
      mixing at interfaces is also analyzed.

PMID- 15169511
TI  - Self-assembled periodical polycrystalline-ZnO/a-C nanolayers on Zn nanowire.
AB  - Zn nanowires with an epitaxial thin surface layer of zinc oxide were dispersed
      onto amorphous carbon films and stored at room temperature. After 1500 h, a self
      organized equal-spaced zinc oxide (approximately 2 nm)/carbon (approximately 2.5
      nm) multilayer structure was found to form outside the Zn nanowire, taking the
      place of the original ZnO surface layer. We carried a systematic study to clarify
      the self-formation mechanism of the periodical multilayers outside the Zn
      nanowire and found out that such a configuration originated from a chemical
      reaction between Zn and CO2 and were formed via a gas phase diffusion-interfacial
      chemical reaction-phase separation process.

PMID- 15169512
TI  - Static and dynamic wetting measurements of single carbon nanotubes.
AB  - Individual carbon nanotubes were immersed and removed from various organic
      liquids using atomic force microscopy. The carbon nanotube-liquid interactions
      could be monitored in situ, and accurate measurements of the contact angle
      between liquids and the nanotube surface were made. These wetting data were used
      to produce Owens and Wendt plots giving the dispersive and polar components of
      the nanotube surface.

PMID- 15169514
TI  - Ab initio calculations in a uniform magnetic field using periodic supercells.
AB  - We present a formulation of ab initio electronic structure calculations in a
      finite magnetic field, which retains the simplicity and efficiency of techniques
      widely used in first principles molecular dynamics simulations, based on plane
      wave basis sets and Fourier transforms. In addition we discuss results obtained
      with this method for the energy spectrum of interacting electrons in quantum
      wells, and for the electronic properties of dense fluid deuterium in a uniform
      magnetic field.

PMID- 15169513
TI  - Direct extraction of the Eliashberg function for electron-phonon coupling: a case
      study of Be(10(-)10).
AB  - We propose a systematic procedure to directly extract the Eliashberg function for
      electron-phonon coupling from high-resolution angle-resolved photoemission
      measurement. The procedure is successfully applied to the Be(10(-)10) surface,
      providing new insights into electron-phonon coupling at this surface. The method
      is shown to be robust against imperfections in experimental data and suitable for
      wider applications.

PMID- 15169515
TI  - Metal-insulator transition in two- and three-dimensional logarithmic plasmas.
AB  - We consider the scaling of the mean square dipole moment in a plasma with
      logarithmic interactions in a two- and three-dimensional systems. In both cases,
      we establish the existence of a low-temperature regime where the mean square
      dipole moment does not scale with system size and a high-temperature regime where
      it does scale with system size. Thus, there is a nonanalytic change in the
      polarizability of the system as a function of temperature and hence a metal
      insulator transition in both cases. The relevance of this transition in three
      dimensions to quantum phase transitions in (2+1)-dimensional systems is briefly
      discussed.

PMID- 15169516
TI  - Realization of an interacting two-valley AlAs bilayer system.
AB  - By using different widths for two AlAs quantum wells comprising a bilayer system,
      we force the X-point conduction-band electrons in the two layers to occupy
      valleys with different Fermi contours, electron effective masses, and g factors.
      Since the occupied valleys are at different X points of the Brillouin zone, the
      interlayer tunneling is negligibly small despite the close electron layer
      spacing. We demonstrate the realization of this system via magnetotransport
      measurements and the observation of a phase-coherent, bilayer nu=1 quantum Hall
      state flanked by a reentrant insulating phase.

PMID- 15169517
TI  - Kondo scaling in the optical response of YbIn1-xAgxCu4.
AB  - Theoretical work on Kondo systems predicts universality in the scaling of
      observable quantities with the Kondo temperature, T(K). Here we report infrared
      frequency optical response measurements of the correlated system YbIn(1-x)AgxCu4.
      We observe that x-dependent variations in the frequency and strength of a low
      energy excitation are related to the x-dependent Kondo temperature. Comparison of
      the inferred trends with existing theory and a model calculation provides a
      framework in which to view these experimental results as scaling phenomena
      arising from local-moment/conduction electron hybridization.

PMID- 15169518
TI  - High efficiency carrier multiplication in PbSe nanocrystals: implications for
      solar energy conversion.
AB  - We demonstrate for the first time that impact ionization (II) (the inverse of
      Auger recombination) occurs with very high efficiency in semiconductor
      nanocrystals (NCs). Interband optical excitation of PbSe NCs at low pump
      intensities, for which less than one exciton is initially generated per NC on
      average, results in the formation of two or more excitons (carrier
      multiplication) when pump photon energies are more than 3 times the NC band gap
      energy. The generation of multiexcitons from a single photon absorption event is
      observed to take place on an ultrafast (picosecond) time scale and occurs with up
      to 100% efficiency depending upon the excess energy of the absorbed photon.
      Efficient II in NCs can be used to considerably increase the power conversion
      efficiency of NC-based solar cells.

PMID- 15169519
TI  - Weak localization in multiterminal networks of diffusive wires.
AB  - We study the quantum transport through networks of diffusive wires connected to
      reservoirs in the Landauer-Buttiker formalism. The elements of the conductance
      matrix are computed by the diagrammatic method. We recover the combination of
      classical resistances and obtain the weak localization corrections. For arbitrary
      networks, we show how the Cooperon must be properly weighted over the different
      wires. Its nonlocality is clearly analyzed. We predict a new geometrical effect
      that may change the sign of the weak localization correction in multiterminal
      geometries.

PMID- 15169520
TI  - Spin splitting of s and p states in single atoms and magnetic coupling in dimers
      on a surface.
AB  - Electronic states of magnetic atoms (Mn, Fe, and Co) and artificially assembled
      dimers (Mn2, Fe2, and Co2) on a NiAl(110) surface were probed by scanning
      tunneling spectroscopy at 17 K. Resonance peaks characteristic of each adsorbed
      species were observed in the unoccupied density of states. Comparison of the
      measured spectra with calculations by density functional theory revealed spin
      splitting in the unoccupied states with s and p characters for the single
      magnetic adatoms and addimers. The magnitude of the resonance splitting for the
      adatoms increased with the calculated values of magnetic moments. The resonance
      structures for the addimers exhibited signatures of their internal magnetic
      coupling.

PMID- 15169521
TI  - Electronic-structure dependence of the electron-phonon interaction in Ag.
AB  - The linewidths of sp- and d-band derived electronic quantum-well states in thin
      films of Ag on Fe(100) are measured as a function of temperature to yield the
      electron-phonon coupling parameters. The results vary by a factor of up to 35
      among the different states. The origin of these huge differences is traced to the
      decay path selection for the various initial states of the holes created by the
      photoemission process. The electron-phonon coupling parameter for the top d-band
      quantum-well state, 0.015+/-0.006, is the smallest ever reported.

PMID- 15169522
TI  - Quantum depinning transition of quantum Hall stripes.
AB  - We examine the effect of disorder on the electromagnetic response of quantum Hall
      stripes using an effective elastic theory to describe their low-energy dynamics,
      and replicas and the Gaussian variational method to handle disorder effects.
      Within our model we demonstrate the existence of a depinning transition at a
      critical partial Landau level filling factor Deltanu(c). For Deltanu<Deltanu(c),
      the pinned state is realized in a replica symmetry breaking (RSB) solution, and
      the frequency-dependent conductivities both perpendicular and parallel to the
      stripes show resonant peaks. These peaks shift to zero frequency as Deltanu-
      >Deltanu(c). For Deltanu> or =Deltanu(c), we find a partial RSB solution in which
      there is free sliding only along the stripe direction. The transition is
      analogous to the Kosterlitz-Thouless phase transition.

PMID- 15169523
TI  - Single- and multigrain nanojunctions with a self-assembled monolayer of
      conjugated molecules.
AB  - Systematic conductivity measurements in nanoscale junctions containing a self
      assembled monolayer of conjugated molecules are reported. Different conductivity
      mechanisms are identified depending on the granularity of the metal used as a
      substrate for assembling the monolayer. Unexpectedly, the energy scale
      controlling the dominant conductance channels is quite low in comparison with the
      molecular level spacing. In single-grain junctions, the dominant conductance
      mechanism is hopping with an energy scale of the order of 10-100 meV determined
      by the nature of the metal contacts. In the case of multigrain junctions,
      additional tunnel conductance is observed with low-energy Coulomb-blockade
      features.

PMID- 15169525
TI  - Hydrogen dominant metallic alloys: high temperature superconductors?
AB  - The arguments suggesting that metallic hydrogen, either as a monatomic or paired
      metal, should be a candidate for high temperature superconductivity are shown to
      apply with comparable weight to alloys of metallic hydrogen where hydrogen is a
      dominant constituent, for example, in the dense group IVa hydrides. The
      attainment of metallic states should be well within current capabilities of
      diamond anvil cells, but at pressures considerably lower than may be necessary
      for hydrogen.

PMID- 15169524
TI  - Dichotomy between nodal and antinodal quasiparticles in underdoped (La2-xSrx)CuO4
      superconductors.
AB  - High resolution angle-resolved photoemission measurements on an underdoped (La(2
      x)Srx)CuO4 system show that, at energies below 70 meV, the quasiparticle peak is
      well defined around the (pi/2,pi/2) nodal region and disappears rather abruptly
      when the momentum is changed from the nodal point to the (pi,0) antinodal point
      along the underlying "Fermi surface." It indicates that there is an extra low
      energy scattering mechanism acting upon the antinodal quasiparticles. We propose
      that this mechanism is the scattering of quasiparticles across the nearly
      parallel segments of the Fermi surface near the antinodes.

PMID- 15169526
TI  - Localization and interaction effects in strongly underdoped La2-xSrxCuO4.
AB  - The in-plane magnetoresistance (MR) in La(2-x)SrxCuO4 films with 0.03< x <0.05
      has been studied in the temperature range 1.6 to 100 K, and in magnetic fields up
      to 14 T, parallel and perpendicular to the CuO2 planes. The behavior of the MR is
      consistent with a predominant influence of interaction effects at high
      temperatures, switching gradually to a regime dominated by spin scattering at low
      T. Weak localization effects are absent. A positive orbital MR appears close to
      the boundary between the antiferromagnetic and the spin-glass phase, suggesting
      the onset of Maki-Thompson superconducting fluctuations deep inside the
      insulating phase.

PMID- 15169527
TI  - Pressure-induced hole doping of the Hg-based cuprate superconductors.
AB  - We investigate the electronic structure and the hole content in the copper-oxygen
      planes of Hg-based high T(c) cuprates for one to four CuO2 layers and hydrostatic
      pressures up to 15 GPa. We find that with the pressure-induced additional number
      of holes of the order of 0.05e the density of states at the Fermi level changes
      by approximately a factor of 2. At the same time, the saddle point is moved to
      the Fermi level accompanied by an enhanced k(z) dispersion. This finding explains
      the pressure behavior of T(c) and leads to the conclusion that the applicability
      of the van Hove scenario is restricted. By comparison with experiment, we
      estimate the coupling constant to be of the order of 1, ruling out the weak
      coupling limit.

PMID- 15169528
TI  - High resolution study of magnetic ordering at absolute zero.
AB  - High resolution pressure measurements in the zero-temperature limit provide a
      unique opportunity to study the behavior of strongly interacting, itinerant
      electrons with coupled spin and charge degrees of freedom. Approaching the
      precision that has become the hallmark of experiments on classical critical
      phenomena, we characterize the quantum critical behavior of the model, elemental
      antiferromagnet chromium, lightly doped with vanadium. We resolve the sharp
      doubling of the Hall coefficient at the quantum critical point and trace the
      dominating effects of quantum fluctuations up to surprisingly high temperatures.

PMID- 15169529
TI  - Unified model for the free-electron avalanche in laser-irradiated dielectrics.
AB  - We develop a model describing the free-electron generation in transparent solids
      under high-intensity laser irradiation. The multiple rate equation model unifies
      key points of detailed kinetic approaches and simple rate equations to a widely
      applicable description, valid on a broad range of time scales. It follows the
      nonstationary energy distribution of electrons on ultrashort time scales as well
      as the transition to the asymptotic avalanche regime for longer irradiations. The
      role of photoionization and impact ionization is clarified in dependence on laser
      pulse duration and intensity.

PMID- 15169531
TI  - Intermediate coupling theory of electronic ferroelectricity.
AB  - We calculate the quantum phase diagram of an extended Falicov-Kimball model for
      one- and two-dimensional systems in the intermediate coupling regime. Even though
      some features of the phase diagram are obtained analytically, the main results
      are calculated with a constrained path Monte Carlo technique. We find that this
      regime is dominated by a Bose-Einstein condensation of excitons with a built-in
      electric polarization. The inclusion of a finite hybridization between the bands
      removes the condensate but reinforces the ferroelectricity.

PMID- 15169530
TI  - Excitonic energy shell structure of self-assembled InGaAs/GaAs quantum dots.
AB  - Performing optical spectroscopy of highly homogeneous quantum dot arrays in
      ultrahigh magnetic fields, an unprecedently well resolved Fock-Darwin spectrum is
      observed. The existence of up to four degenerate electronic shells is
      demonstrated where the magnetic field lifts the initial degeneracies, which
      reappear when levels with different angular momenta come into resonance. The
      resulting level shifting and crossing pattern also show evidence of many-body
      effects such as the mixing of configurations and exciton condensation at the
      resonances.

PMID- 15169532
TI  - Stimulated desorption of cations from pristine and acidic low-temperature water
      ice surfaces.
AB  - Electron-impact ionization of low-temperature water ice leads to H+, H+2, and
      H+(H2O)(n=1-8) desorption. The 22 eV H+ desorption threshold is correlated with
      localized 2-hole 1-electron and 2-hole final states which Coulomb explode, while
      the 22 eV H+2 threshold is due to H2O+ unimolecular dissociation. The 70 eV
      primary cluster ion threshold is consistent with holes in the 2a(1) level and
      secondary ionization channels. All cation yields are sensitive to local
      structural changes and probe surface acidity. The cluster size distribution
      indicates hole-hole screening distances of 1-2 nm.

PMID- 15169533
TI  - Superdense coding of quantum states.
AB  - We describe a method for nonobliviously communicating a 2l-qubit quantum state by
      physically transmitting l+o(l) qubits, and by consuming l ebits of entanglement
      plus some shared random bits. In the nonoblivious scenario, the sender has a
      classical description of the state to be communicated. Our method can be used to
      communicate states that are pure or entangled with the sender's system; l+o(l)
      and 3l+o(l) shared random bits are sufficient, respectively.

PMID- 15169534
TI  - Perfect state transfer in quantum spin networks.
AB  - We propose a class of qubit networks that admit the perfect state transfer of any
      quantum state in a fixed period of time. Unlike many other schemes for quantum
      computation and communication, these networks do not require qubit couplings to
      be switched on and off. When restricted to N-qubit spin networks of identical
      qubit couplings, we show that 2log3N is the maximal perfect communication
      distance for hypercube geometries. Moreover, if one allows fixed but different
      couplings between the qubits, then perfect state transfer can be achieved over
      arbitrarily long distances in a linear chain.

PMID- 15169535
TI  - Symmetry induced coupling of cortical feature maps.
AB  - The mammalian visual cortex maps retinal position (retinotopy) and orientation
      preference (OP) across its surface. Simultaneous measurements in vivo suggest
      that positive correlation exists between the location of dislocations in these
      two maps, contradicting the predictions of classical dimension reduction models.
      Model symmetries exert a significant influence on pattern development. However,
      classical models for cortical map formation have inappropriate symmetry
      properties. By applying equivariant bifurcation theory we derive symmetry
      induced, model independent coupling of the OP and retinotopic maps and show that
      this coupling replicates observations.

PMID- 15169536
TI  - Permeative flows in cholesteric liquid crystals.
AB  - We use lattice Boltzmann simulations to solve the Beris-Edwards equations of
      motion for a cholesteric liquid crystal subjected to Poiseuille flow along the
      direction of the helical axis (permeative flow). The results allow us to clarify
      and extend the approximate analytic treatments currently available. We find that
      if the cholesteric helix is pinned at the boundaries there is an enormous
      viscosity increase. If, instead, the helix is free the velocity profile is
      flattened, but the viscosity is essentially unchanged. We highlight the
      importance of secondary flows, and, for higher flow velocities, we identify a
      flow-induced double twist structure in the director field--reminiscent of the
      texture characteristic of blue phases.

PMID- 15169537
TI  - Dissociation of a product of a surface reaction in the gas phase: XeF2 reaction
      with Si.
AB  - Xenon difluoride interacts with Si(100)2 x 1 by atom abstraction, whereby a
      dangling bond abstracts a F atom from XeF2, scattering the complementary XeF.
      Partitioning of the reaction exothermicity produces sufficient XeF rovibrational
      excitation for dissociation to occur. The resulting F and Xe atoms are shown to
      arise from dissociation of XeF in the gas phase by demonstrating that the angle
      resolved velocity distributions of F, Xe, and XeF conserve momentum, energy, and
      mass. This experiment documents the first observation of dissociation of a
      surface reaction product in the gas phase.

PMID- 15169538
TI  - Prototypical single-molecule chemical-field-effect transistor with nanometer
      sized gates.
AB  - A prototypical single-molecule chemical-field-effect transistor is presented, in
      which the current through a hybrid-molecular diode is modified by nanometer-sized
      charge transfer complexes covalently linked to a molecule in an STM junction. The
      effect is attributed to an interface dipole which shifts the substrate work
      function by approximately 120 meV. It is induced by the complexes from electron
      acceptors covalently bound to the molecule in the gap and electron donors coming
      from the ambient fluid. This proof of principle is regarded as a major step
      towards monomolecular electronic devices.

PMID- 15169540
TI  - Comment on "Ferrofluids as thermal ratchets".

PMID- 15169539
TI  - Networks, dynamics, and modularity.
AB  - The identification of general principles relating structure to dynamics has been
      a major goal in the study of complex networks. We propose that the special case
      of linear network dynamics provides a natural framework within which a number of
      interesting yet tractable problems can be defined. We report the emergence of
      modularity and hierarchical organization in evolved networks supporting
      asymptotically stable linear dynamics. Numerical experiments demonstrate that
      linear stability benefits from the presence of a hierarchy of modules and that
      this architecture improves the robustness of network stability to random
      perturbations in network structure. This work illustrates an approach to network
      science which is simultaneously structural and dynamical in nature.

PMID- 15169542
TI  - Inositol trisphosphate analogues selective for types I and II inositol
      trisphosphate receptors exert differential effects on vasopressin-stimulated Ca2+
      inflow and Ca2+ release from intracellular stores in rat hepatocytes.
AB  - Previous studies have shown that adenophostin A is a potent initiator of the
      activation of SOCs (store-operated Ca2+ channels) in rat hepatocytes, and have
      suggested that, of the two subtypes of Ins(1,4,5)P3 receptor predominantly
      present in rat hepatocytes [Ins(1,4,5)P3R1 (type I receptor) and Ins(1,4,5)P3R2
      (type II receptor)], Ins(1,4,5)P3R1s are required for SOC activation. We compared
      the abilities of Ins(1,4,6)P3 [with higher apparent affinity for Ins(1,4,5)P3R1]
      and Ins(1,3,6)P3 and Ins(1,2,4,5)P4 [with higher apparent affinities for
      Ins(1,4,5)P3R2] to activate SOCs. The Ins(1,4,5)P3 analogues were microinjected
      into single cells together with fura 2, and dose-response curves for the
      activation of Ca2+ inflow and Ca2+ release from intracellular stores obtained for
      each analogue. The concentration of Ins(1,4,6)P3 which gave half-maximal
      stimulation of Ca2+ inflow was substantially lower than that which gave half
      maximal stimulation of Ca2+ release. By contrast, for Ins(1,3,6)P3 and
      Ins(1,2,4,5)P3, the concentration which gave half-maximal stimulation of Ca2+
      inflow was substantially higher than that which gave half-maximal stimulation of
      Ca2+ release. The distribution of Ins(1,4,5)P3R1 and Ins(1,4,5)P3R2 in rat
      hepatocytes cultured under the same conditions as those employed for the
      measurement of Ca2+ inflow and release was determined by immunofluorescence.
      Ins(1,4,5)-P3R1s were found predominantly at the cell periphery, whereas
      Ins(1,4,5)P3R2s were found at the cell periphery, the cell interior and nucleus.
      It is concluded that the idea that a small region of the endoplasmic reticulum
      enriched in Ins(1,4,5)P3R1 is required for the activation of SOCs is consistent
      with the present results for hepatocytes.

PMID- 15169544
TI  - Substance abuse and pharmacy practice: what the community pharmacist needs to
      know about drug abuse and dependence.
AB  - Pharmacists, the most accessible of health care professionals, are well
      positioned to help prevent and treat substance use disorders and should prepare
      themselves to perform these functions. New research improves our knowledge about
      the pharmacological and behavioral risks of drug abuse, supports the clinical
      impression that drug dependence is associated with long-lasting neurochemical
      changes, and demonstrates effective pharmacological treatments for certain kinds
      of drug dependencies. The profession is evolving. Pharmacists are engaging in new
      practice behaviors such as helping patients manage their disease states.
      Collaborative practice agreements and new federal policies set the stage for
      pharmacists to assist in the clinical management of opioid and other drug
      dependencies. Pharmacists need to be well informed about issues related to
      addiction and prepared not only to screen, assess, and refer individual cases and
      to collaborate with physicians caring for chemically dependent patients, but also
      to be agents of change in their communities in the fight against drug abuse.At
      the end of this article the pharmacist will be better able to:1. Explain the
      disease concept of chemical dependence2. Gather the information necessary to
      conduct a screen for chemical dependence3. Inform patients about the treatment
      options for chemical dependence4. Locate resources needed to answer questions
      about the effects of common drugs of abuse (alcohol, marijuana, narcotics,
      "ecstasy", and cocaine)5. Develop a list of local resources for drug abuse
      treatment6. Counsel parents who are concerned about drug use by their children7.
      Counsel individuals who are concerned about drug use by a loved one.8. Counsel
      individuals who are concerned about their own drug use

PMID- 15169543
TI  - Assessing and improving needle exchange programs: gaps and problems in the
      literature.
AB  - Based on an extensive review of the needle exchange program (NEP) literature, the
      author sought to identify weaknesses in NEP evaluations published to date.
      Surprisingly, it was apparent that NEP researchers often fail to: (1) collect
      comparison/change data; (2) agree on appropriate and consistent dependent
      variables to measure; (3) use valid and reliable measurement instruments; (4)
      present clear operational definitions; (5) analyze outcome measures by
      gender/race/social context; (6) provide data on type of drug injected as it
      relates to risky drug and sexual behaviors; (7) measure HIV/AIDS knowledge; or,
      (8) clearly articulate desired NEP outcomes. Suggestions for future research are
      included, and conclusions about the overall state of NEP evaluative research are
      drawn.

PMID- 15169545
TI  - Return Rates for Needle Exchange Programs: A Common Criticism Answered.
AB  - This study searched the available needle exchange program (NEP) literature for
      return rate data. A total of 26 articles were found. The overall worldwide return
      rate was 90%, although this ranged from a low of 15% to a high of 112%. U.S. NEP
      return rates were gathered from only eight studies, indicating a clear need for
      more data, although U.S. return rates were comparable to those from NEPs outside
      of the U.S.One underlying assumption made by opponents of NEPs is that IDUs will
      not return needles to the distribution site, thereby potentially increasing the
      risk of health problems to the surrounding community from exposure to
      contaminated needles. This study's results suggest that NEPs are relatively
      successful in taking in used needles, although it is generally unclear where the
      needles were originally acquired, and if IDUs return their own needles, or are
      returning needles for a social network. Ways for AIDS Service Organizations to
      capitalize on these brief encounters with IDUs, as well as public policy
      implications of the findings, are discussed.

PMID- 15169546
TI  - Harm Reduction Journal.

PMID- 15169548
TI  - Patterns of delays amongst pulmonary tuberculosis patients in Lagos, Nigeria.
AB  - BACKGROUND: Pulmonary tuberculosis continues to increase due to late patient
      presentation. The study was conducted at a chest clinic of a general hospital in
      Lagos, Nigeria, to investigate patterns of delays before treatment amongst
      tuberculosis patients. METHODS: Longitudinal recruitment using a health worker
      administered protocol to determine time interval from onset of symptoms to
      initiation of treatment. Presentation to a health facility after 30 days of the
      onset of symptoms was classified as patient delay. Doctor delay was when patients
      stayed for more than 15 days with the referring doctor. RESULTS: One hundred and
      forty-one patients were recruited. The mean age was 29.5 +/- 11.0 years, 89 (63%)
      were males and 52 (37%) were females. One hundred and sixteen (82%) had positive
      smears. One hundred and seventeen (83%) delayed their seeking help from health
      facilities longer than one month after the onset of symptoms. The median patient
      delay was eight weeks; median doctor delay was one week, median treatment delay
      was one week and the median total delay was 10 weeks. Doctor delay was observed
      in 19 (13%) patients. Patient delay was the most frequent type of delay observed
      and was the major contributor to the overall total delay. Patient delay was not
      significantly associated with patients' socio-demographic characteristics such as
      age, gender and educational level. CONCLUSION: Majority of TB patients at this
      centre did not present early to health facilities and continue to serve as
      reservoirs of infection. Patient education on the disease may help reduce delays
      in starting treatment.

PMID- 15169547
TI  - Prevalence of facet joint pain in chronic spinal pain of cervical, thoracic, and
      lumbar regions.
AB  - BACKGROUND: Facet joints are a clinically important source of chronic cervical,
      thoracic, and lumbar spine pain. The purpose of this study was to systematically
      evaluate the prevalence of facet joint pain by spinal region in patients with
      chronic spine pain referred to an interventional pain management practice.
      METHODS: Five hundred consecutive patients with chronic, non-specific spine pain
      were evaluated. The prevalence of facet joint pain was determined using
      controlled comparative local anesthetic blocks (1% lidocaine or 1% lidocaine
      followed by 0.25% bupivacaine), in accordance with the criteria established by
      the International Association for the Study of Pain (IASP). The study was
      performed in the United States in a non-university based ambulatory
      interventional pain management setting. RESULTS: The prevalence of facet joint
      pain in patients with chronic cervical spine pain was 55% 5(95% CI, 49%-61%),
      with thoracic spine pain was 42% (95% CI, 30%-53%), and in with lumbar spine pain
      was 31% (95% CI, 27%-36%). The false-positive rate with single blocks with
      lidocaine was 63% (95% CI, 54%-72%) in the cervical spine, 55% (95% CI, 39%-78%)
      in the thoracic spine, and 27% (95% CI, 22%-32%) in the lumbar spine. CONCLUSION:
      This study demonstrated that in an interventional pain management setting, facet
      joints are clinically important spinal pain generators in a significant
      proportion of patients with chronic spinal pain. Because these patients typically
      have failed conservative management, including physical therapy, chiropractic
      treatment and analgesics, they may benefit from specific interventions designed
      to manage facet joint pain.

PMID- 15169549
TI  - The level of non-citation of articles within a journal as a measure of quality: a
      comparison to the impact factor.
AB  - BACKGROUND: Current methods of measuring the quality of journals assume that
      citations of articles within journals are normally distributed. Furthermore using
      journal impact factors to measure the quality of individual articles is flawed if
      citations are not uniformly spread between articles. The aim of this study was to
      assess the distribution of citations to articles and use the level of non
      citation of articles within a journal as a measure of quality. This ranking
      method is compared with the impact factor, as calculated by ISI(R). METHODS:
      Total citations gained by October 2003, for every original article and review
      published in current immunology (13125 articles; 105 journals) and surgical
      (17083 articles; 120 journals) fields during 2001 were collected using ISI(R) Web
      of Science. RESULTS: The distribution of citation of articles within an
      individual journal is mainly non-parametric throughout the literature. One sixth
      (16.7%; IQR 13.6-19.2) of articles in a journal accrue half the total number of
      citations to that journal. There was a broader distribution of citation to
      articles in higher impact journals and in the field of immunology compared to
      surgery. 23.7% (IQR 14.6-42.4) of articles had not yet been cited. Levels of non
      citation varied between journals and subject fields. There was a significant
      negative correlation between the proportion of articles never cited and a
      journal's impact factor for both immunology (rho = -0.854) and surgery journals
      (rho = -0.924). CONCLUSION: Ranking journals by impact factor and non-citation
      produces similar results. Using a non-citation rate is advantageous as it creates
      a clear distinction between how citation analysis is used to determine the
      quality of a journal (low level of non-citation) and an individual article
      (citation counting). Non-citation levels should therefore be made available for
      all journals.

PMID- 15169550
TI  - Incongruence between test statistics and P values in medical papers.
AB  - BACKGROUND: Given an observed test statistic and its degrees of freedom, one may
      compute the observed P value with most statistical packages. It is unknown to
      what extent test statistics and P values are congruent in published medical
      papers. METHODS: We checked the congruence of statistical results reported in all
      the papers of volumes 409-412 of Nature (2001) and a random sample of 63 results
      from volumes 322-323 of BMJ (2001). We also tested whether the frequencies of the
      last digit of a sample of 610 test statistics deviated from a uniform
      distribution (i.e., equally probable digits). RESULTS: 11.6% (21 of 181) and
      11.1% (7 of 63) of the statistical results published in Nature and BMJ
      respectively during 2001 were incongruent, probably mostly due to rounding,
      transcription, or type-setting errors. At least one such error appeared in 38%
      and 25% of the papers of Nature and BMJ, respectively. In 12% of the cases, the
      significance level might change one or more orders of magnitude. The frequencies
      of the last digit of statistics deviated from the uniform distribution and
      suggested digit preference in rounding and reporting. CONCLUSIONS: This
      incongruence of test statistics and P values is another example that statistical
      practice is generally poor, even in the most renowned scientific journals, and
      that quality of papers should be more controlled and valued.

PMID- 15169551
TI  - Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a
      quantitative trait locus for fetal hemoglobin expression in adults.
AB  - BACKGROUND: Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a
      common multifactorial trait characterized by a modest increase of fetal
      hemoglobin levels in adults. We previously localized a Quantitative Trait Locus
      for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the
      strategy of positional cloning and a means towards identification of the specific
      genetic alteration in this family, a thorough annotation of the candidate
      interval based on a strategy of in silico / wet biology approach with comparative
      genomics was conducted. RESULTS: The ~1.5 Mb candidate region was shown to
      contain five protein-coding genes. We discovered a very large uncharacterized
      gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four
      previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also
      identified several genes that do not appear to be protein coding, and generated
      17 kb of novel transcript sequence data from re-sequencing 97 EST clones.
      CONCLUSION: Detailed and thorough annotation of this 1.5 Mb interval in 6q
      confirms a high level of aberrant transcripts in testicular tissue. The candidate
      interval was shown to exhibit an extraordinary level of alternate splicing - 19
      transcripts were identified for the 5 protein coding genes, but it appears that a
      significant portion (14/19) of these alternate transcripts did not have an open
      reading frame, hence their functional role is questionable. These transcripts may
      result from aberrant rather than regulated splicing.

PMID- 15169552
TI  - The effect of selective phosphodiesterase inhibitors, alone and in combination,
      on a murine model of allergic asthma.
AB  - BACKGROUND: The anti-inflammatory effects of the selective phosphodiesterase
      (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5)
      were examined in a murine model of allergic asthma. These compounds were used
      alone and in combination to determine any potential synergism, with dexamethasone
      included as a positive control. METHODS: Control and ovalbumin sensitised Balb/C
      mice were administered orally with each of the possible combinations of drugs at
      a dose of 3 mg/Kg for 10 days. RESULTS: When used alone, RO 20-1724 significantly
      reduced eosinophil influx into lungs and lowered tumour necrosis factor-alpha,
      interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when
      compared to untreated mice. Treatment with cilostazol or sildenafil did not
      significantly inhibit any markers of inflammation measured. Combining any of
      these PDE inhibitors produced no additive or synergistic effects. Indeed, the
      anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of
      either cilostazol or sildenafil. CONCLUSIONS: These results suggest that
      concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti
      inflammatory effectiveness of a PDE 4 inhibitor.

PMID- 15169553
TI  - Increased mortality associated with HTLV-II infection in blood donors: a
      prospective cohort study.
AB  - BACKGROUND: HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and 
      II are associated with HTLV-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). Several published reports suggest that HTLV-I may lead to decreased
      survival, but HTLV-II has not previously been associated with mortality. RESULTS:
      We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls
      enrolled in a prospective cohort study of U.S. blood donors followed biannually
      since 1992. Proportional hazards models yielded hazard ratios (HRs) for the
      association between mortality and HTLV infection, controlling for sex,
      race/ethnicity, age, income, educational level, blood center, smoking, injection
      drug use history, alcohol intake, hepatitis C status and autologous donation.
      After a median follow-up of 8.6 years, there were 45 confirmed subject deaths.
      HTLV-I infection did not convey a statistically significant excess risk of
      mortality (unadjusted HR 1.9, 95%CI 0.8-4.4; adjusted HR 1.9, 95%CI 0.8-4.6).
      HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5
      5.5) and in the adjusted model (HR 2.3, 95%CI 1.1-4.9). No single cause of death
      appeared responsible for the HTLV-II effect. CONCLUSIONS: After adjusting for
      known and potential confounders, HTLV-II infection is associated with increased
      mortality among healthy blood donors. If replicated in other cohorts, this
      finding has implications for both HTLV pathogenesis and counseling of infected
      persons.

PMID- 15169554
TI  - Evolution of the HIV-1 envelope glycoproteins with a disulfide bond between gp120
      and gp41.
AB  - BACKGROUND: We previously described the construction of an HIV-1 envelope
      glycoprotein complex (Env) that is stabilized by an engineered intermolecular
      disulfide bond (SOS) between gp120 and gp41. The modified Env protein
      antigenically mimics the functional wild-type Env complex. Here, we explore the
      effects of the covalent gp120 - gp41 interaction on virus replication and
      evolution. RESULTS: An HIV-1 molecular clone containing the SOS Env gene was only
      minimally replication competent, suggesting that the engineered disulfide bond
      substantially impaired Env function. However, virus evolution occurred in cell
      culture infections, and it eventually always led to elimination of the
      intermolecular disulfide bond. In the course of these evolution studies, we
      identified additional and unusual second-site reversions within gp41.
      CONCLUSIONS: These evolution paths highlight residues that play an important role
      in the interaction between gp120 and gp41. Furthermore, our results suggest that
      a covalent gp120 - gp41 interaction is incompatible with HIV-1 Env function,
      probably because this impedes conformational changes that are necessary for
      fusion to occur, which may involve the complete dissociation of gp120 from gp41.

PMID- 15169555
TI  - Establishment of a novel CCR5 and CXCR4 expressing CD4+ cell line which is highly
      sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4
      antagonists.
AB  - BACKGROUND: CCR5 and CXCR4 are the two main coreceptors essential for HIV entry.
      Therefore, these chemokine receptors have become important targets in the search
      for anti-HIV agents. Here, we describe the establishment of a novel CD4+ cell
      line, U87.CD4.CCR5.CXCR4, stably expressing both CCR5 and CXCR4 at the cell
      surface. RESULTS: In these cells, intracellular calcium signalling through both
      receptors can be measured in a single experiment upon the sequential addition of
      CXCR4- and CCR5-directed chemokines. The U87.CD4.CCR5.CXCR4 cell line reliably
      supported HIV-1 infection of diverse laboratory-adapted strains and primary
      isolates with varying coreceptor usage (R5, X4 and R5/X4) and allows to
      investigate the antiviral efficacy of combined CCR5 and CXCR4 blockade. The
      antiviral effects recorded in these cells with the CCR5 antagonist SCH-C and the
      CXCR4 antagonist AMD3100 were similar to those noted in the single CCR5- or CXCR4
      transfected U87.CD4 cells. Furthermore, the combination of both inhibitors
      blocked the infection of all evaluated HIV-1 strains and isolates. CONCLUSIONS:
      Thus, the U87.CD4.CCR5.CXCR4 cell line should be useful in the evaluation of CCR5
      and CXCR4 antagonists with therapeutic potential and combinations thereof.

PMID- 15169556
TI  - Multi-faceted, multi-versatile microarray: simultaneous detection of many viruses
      and their expression profiles.
AB  - There are hundreds of viruses that infect different human organs and cause
      diseases. Some fatal emerging viral infections have become serious public health
      issues worldwide. Early diagnosis and subsequent treatment are therefore
      essential for fighting viral infections. Current diagnostic techniques frequently
      employ polymerase chain reaction (PCR)-based methods to quickly detect the
      pathogenic viruses and establish the etiology of the disease or illness. However,
      the fast PCR method suffers from many drawbacks such as a high false-positive
      rate and the ability to detect only one or a few gene targets at a time.
      Microarray technology solves the problems of the PCR limitations and can be
      effectively applied to all fields of molecular medicine. Recently, a report in
      Retrovirology described a multi-virus DNA array that contains more than 250 open
      reading frames from eight human viruses including human immunodeficiency virus
      type 1. This array can be used to detect multiple viral co-infections in cells
      and in vivo. Another benefit of this kind of multi-virus array is in studying
      promoter activity and viral gene expression and correlating such readouts with
      the progression of disease and reactivation of latent infections. Thus, the virus
      DNA-chip development reported in Retrovirology is an important advance in
      diagnostic application which could be a potent clinical tool for characterizing
      viral co-infections in AIDS as well as other patients.

PMID- 15169558
TI  - Retrovirology and young Turks...

PMID- 15169557
TI  - Use of a multi-virus array for the study of human viral and retroviral pathogens:
      gene expression studies and ChIP-chip analysis.
AB  - BACKGROUND: Since the discovery of human immunodeficiency virus (HIV-1) twenty
      years ago, AIDS has become one of the most studied diseases. A number of viruses
      have subsequently been identified to contribute to the pathogenesis of HIV and
      its opportunistic infections and cancers. Therefore, a multi-virus array
      containing eight human viruses implicated in AIDS pathogenesis was developed and
      its efficacy in various applications was characterized. RESULTS: The amplified
      open reading frames (ORFs) of human immunodeficiency virus type 1, human T cell
      leukemia virus types 1 and 2, hepatitis C virus, Epstein-Barr virus, human
      herpesvirus 6A and 6B, and Kaposi's sarcoma-associated herpesvirus were spotted
      on glass slides and hybridized to DNA and RNA samples. Using a random priming
      method for labeling genomic DNA or cDNA probes, we show specific detection of
      genomic viral DNA from cells infected with the human herpesviruses, and
      effectively demonstrate the inhibitory effects of a cellular cyclin dependent
      kinase inhibitor on viral gene expression in HIV-1 and KSHV latently infected
      cells. In addition, we coupled chromatin immunoprecipitation with the virus chip
      (ChIP-chip) to study cellular protein and DNA binding. CONCLUSIONS: An amplicon
      based virus chip representing eight human viruses was successfully used to
      identify each virus with little cross hybridization. Furthermore, the identity of
      both viruses was correctly determined in co-infected cells. The utility of the
      virus chip was demonstrated by a variety of expression studies. Additionally,
      this is the first demonstrated use of ChIP-chip analysis to show specific binding
      of proteins to viral DNA, which, importantly, did not require further
      amplification for detection.

PMID- 15169559
TI  - Development of the Physical Activity Interactive Recall (PAIR) for Aboriginal
      children.
AB  - BACKGROUND: Aboriginal children in Canada are at increased risk for type 2
      diabetes. Given that physical inactivity is an important modifiable risk factor
      for type 2 diabetes, prevention efforts targeting Aboriginal children include
      interventions to enhance physical activity involvement. These types of
      interventions require adequate assessment of physical activity patterns to
      identify determinants, detect trends, and evaluate progress towards intervention
      goals. The purpose of this study was to develop a culturally appropriate
      interactive computer program to self-report physical activity for Kanien'keha:ka
      (Mohawk) children that could be administered in a group setting. This was an
      ancillary study of the ongoing Kahnawake Schools Diabetes Prevention Project
      (KSDPP). METHODS: During Phase I, focus groups were conducted to understand how
      children describe and graphically depict type, intensity and duration of physical
      activity. Sixty-six students (40 girls, 26 boys, mean age = 8.8 years, SD = 1.8)
      from four elementary schools in three eastern Canadian Kanien'keha:ka communities
      participated in 15 focus groups. Children were asked to discuss and draw about
      physical activity. Content analysis of focus groups informed the development of a
      school-day and non-school-day version of the physical activity interactive recall
      (PAIR). In Phase II, pilot-tests were conducted in two waves with 17 and 28
      children respectively to assess the content validity of PAIR. Observation,
      videotaping, and interviews were conducted to obtain children's feedback on PAIR
      content and format. RESULTS: Children's representations of activity type and
      activity intensity were used to compile a total of 30 different physical activity
      and 14 non-physical activity response choices with accompanying intensity
      options. Findings from the pilot tests revealed that Kanien'keha:ka children
      between nine and 13 years old could answer PAIR without assistance. Content
      validity of PAIR was judged to be adequate. PAIR was judged to be comprehensive,
      acceptable, and enjoyable by the children. CONCLUSIONS: Results indicate that
      PAIR may be acceptable to children between nine and 13 years old, with most in
      this age range able to complete PAIR without assistance. The flexibility of its
      programming makes PAIR an easily adaptable tool to accommodate diverse
      populations, different seasons, and changing trends in physical activity
      involvement.

PMID- 15169560
TI  - The influence of self-efficacy and outcome expectations on the relationship
      between perceived environment and physical activity in the workplace.
AB  - BACKGROUND: Recent research and commentary contends that ecological approaches
      may be particularly useful for understanding and promoting physical activity
      participation in various settings including the workplace. Yet within the
      physical activity domain there is a lack of understanding of how ecological
      environment factors influence behaviour. Thus, the purpose of this study was to
      examine the relationships between perceived environment, social-cognitive
      variables, and physical activity behaviour. METHODS: Participants (N = 897) were
      employees from three large worksites who completed self-report inventories
      containing measures of self-efficacy, outcome expectations, perceptions of the
      workplace environment (PWES), and physical activity behaviour during both leisure
      time and incorporated throughout the workday. RESULTS: Results of both bivariate
      and multiple regression analyses indicated the global PWES scores had a limited
      association with leisure-time physical activity (R2adj =.01). Sequential
      regression analyses supported a weak association between physical activity
      incorporated in the workplace and PWES (R2adj =.04) and the partial mediation of
      self-efficacy on the relationship between PWES and workplace physical activity
      (variance accounted for reduced to R2adj =.02 when self-efficacy was controlled).
      CONCLUSION: Overall, the results of the present investigation indicate that self
      efficacy acted as a partial mediator of the relationship between perceived
      environment and workplace physical activity participation. Implications of the
      findings for physical activity promotion using ecological-based approaches, and
      future directions for research from this perspective in worksite settings are
      discussed.

PMID- 15169561
TI  - The relationship between physical fitness and clustered risk, and tracking of
      clustered risk from adolescence to young adulthood: eight years follow-up in the
      Danish Youth and Sport Study.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is usually caused by high levels of
      many risk factors simultaneously over many years. Therefore, it is of great
      interest to study if subjects stay within rank order over time in both the
      biological risk factors and the behaviour that influences these risk factors.
      Many studies have described stability (tracking) in single risk factors,
      especially in children where hard endpoints are lacking, but few have analysed
      tracking in clustered risk. METHODS: Two examinations were conducted 8 years
      apart. The first time, 133 males and 172 females were 16-19 years of age. Eight
      years later, 98 males and 137 females participated. They were each time ranked
      into quartiles by sex in four CVD risk factors all related to the metabolic
      syndrome. Risk factors were the ratio between total cholesterol and HDL,
      triglyceride, systolic BP and body fat. The upper quartile was defined as being
      at risk, and if a subject had two or more risk factors, he/she was defined as a
      case (15-20 % of the subjects). Odds ratios (OR) for being a case was calculated
      between quartiles of fitness in both cross-sectional studies. The stability of
      combined risk was calculated as the OR between cases and non-cases at the first
      examination to be a case at the second examination. RESULTS: ORs for having two
      or more risk factors between quartiles of fitness were 3.1, 3.8 and 4.9 for
      quartiles two to four, respectively. At the second examination, OR were 0.7, 3.5
      and 4.9, respectively. The probability for "a case" at the first examination to
      be "a case" at the second was 6.0. CONCLUSIONS: The relationship between an
      exposure like physical fitness and CVD risk factors is much stronger when
      clustering of risk factors are analysed compared to the relationship to single
      risk factors. The stability over time in multiple risk factors analysed together
      is strong. This relationship should be seen in the light of moderate or weak
      tracking of single risk factors, and is strong evidence for early intervention in
      children where risk factors cluster.

PMID- 15169562
TI  - The quality of girls' diets declines and tracks across middle childhood.
AB  - BACKGROUND: Food group intakes by US children are below recommendations and
      micronutrient inadequacies have been reported. There are few longitudinal data
      that focus on developmental changes in food and nutrient intake from early to
      middle childhood. We examined changes in nutrient and food group intakes over
      time and the tracking of intakes across middle childhood in a longitudinal sample
      of girls. METHODS: Three multiple-pass 24-hour diet recalls were conducted in a
      sample of 181 non-Hispanic White girls at ages 5, 7, and 9 years. Food and
      nutrient data were averaged across 3 days. Analyses of time effects were
      conducted using repeated measures analysis of variance and tracking of intakes
      was assessed via rank analysis. RESULTS: We found significant decreases in
      nutrient densities (intakes per 1000 kcal) of vitamins C and D, calcium,
      phosphorus, magnesium and zinc at age 9. Girls maintained their relative quartile
      positions for these micronutrients from ages 5-9. Analysis of food group data
      showed similar trends. At age 9, significantly fewer girls were meeting the
      recommendations for dairy, fruit and vegetable servings than at age 5 and girls
      also tended to remain in their respective quartiles over time, especially for
      fruit and dairy intakes. CONCLUSIONS: These results highlight the importance of
      developing healthy eating practices during early childhood when caretakers have
      considerable control over children's food intake.

PMID- 15169563
TI  - Activities Contributing to Total Energy Expenditure in the United States: Results
      from the NHAPS Study.
AB  - BACKGROUND: Physical activity is increasingly recognized as an important factor
      influencing health and disease status. Total energy expenditure, both low
      intensity and high-intensity, contributes to maintenance of healthy body weight.
      This paper presents the results of a quantitative approach to determining the
      activities that contribute to total energy expenditure in the United States.
      METHODS: Data from the National Human Activity Pattern Survey (NHAPS) were used.
      In 1992-1994 the NHAPS sampled 4,185 females and 3,330 males, aged 18 years and
      over, weighted to be representative of the 48 contiguous United States. A
      detailed report of each activity performed in the previous 24 hours was obtained.
      A score was created for each activity, by multiplying duration and intensity for
      each individual and summing across individuals. This score was then used to rank
      each activity according to its contribution to total population energy
      expenditure, for the total sample and separately for each gender, race, age,
      region, and season. RESULTS: This analysis reveals our society to be primarily
      sedentary; leisure time physical activity contributed only approximately 5% of
      the population's total energy expenditure. Not counting sleeping, the largest
      contributor to energy expenditure was "Driving a car", followed by "Office work"
      and "Watching TV". Household activities accounted for 20.1% and 33.3% of energy
      expenditure for males and females respectively. CONCLUSION: The information
      presented in this paper may be useful in identifying common activities that could
      be appropriate targets for behavioral interventions to increase physical
      activity.

PMID- 15169565
TI  - A comprehensive system of pharmaceutical care for drug misusers.
AB  - This article outlines the evolution of a community pharmacy-based supervised
      consumption of methadone program in Grater Glasgow. The formalization of this
      program in 1994 promoted full patient compliance with the methadone regimen and
      reduced seepage of the drug to the illicit market. 184 of the area's 215
      community pharmacies now dispense methadone for the treatment of opiate
      dependence. Of these, 173 have a supplementary contract with the local health
      board to supervise the consumption of methadone on their premises. In addition 15
      of "methadone" pharmacists are involved in the provision of a pharmacy based
      needle exchange scheme. This has been shown to be the most efficient and cost
      effective method of delivering clean injecting equipment to injecting drug users
      in the Greater Glasgow area. Glasgow's pharmacists' have now been involved in the
      methadone and needle exchange programs for more than ten years. The support
      needed by pharmacists and the steps that have been put in place to provide this
      level of commitment are described. The development of the Glasgow pharmacy based
      services to drug users has had a major impact on practice elsewhere in the United
      Kingdom.

PMID- 15169564
TI  - Validity, reliability and responsiveness of the "Schedule for the Evaluation of
      Individual Quality of Life-Direct Weighting" (SEIQoL-DW) in congenital heart
      disease.
AB  - BACKGROUND: The 'Schedule for the Evaluation of Individual Quality of Life-Direct
      Weighting' (SEIQoL-DW) is an instrument developed to measure individual quality
      of life. Although this instrument has been used in numerous studies, data on
      validity and reliability are sparse. This study aimed to examine aspects of
      validity, reliability and responsiveness of the SEIQoL-DW on data obtained in
      adults with congenital heart disease, by using the new standards of psychological
      testing. METHODS: We evaluated validity evidence based on test content, internal
      structure, and relations to other variables, as well as the stability and
      responsiveness of the SEIQoL-DW. Evidence was provided by both theoretical
      considerations and empirical data. Empirical data were acquired from two studies.
      Firstly, using a cross-sectional study design, we included 629 patients with
      congenital heart disease. Secondly, 130 of the 629 initially included patients
      readministered the questionnaires approximately one year after the first data
      collection. In addition to the SEIQoL-DW, linear analog scales were used to
      assess overall quality of life and perceived health. RESULTS: We found that the
      SEIQoL-DW is not a valid measure of quality of life, but rather assesses
      determinants that contribute to individuals' quality of life. The SEIQoL-DW
      consistently proved to be valid and reliable to assess those determinants.
      However, responsiveness in patients with congenital heart disease may be
      problematic. CONCLUSION: Based on theoretical and empirical considerations, the
      SEIQoL-DW cannot be considered as a quality of life instrument. Nonetheless, it
      is a valid and reliable instrument to explore determinants for patients' quality
      of life.

PMID- 15169566
TI  - Substance use during pregnancy: time for policy to catch up with research.
AB  - The phenomenon of substance abuse during pregnancy has fostered much controversy,
      specifically regarding treatment vs. punishment. Should the pregnant mother who
      engages in substance abuse be viewed as a criminal or as someone suffering from
      an illness requiring appropriate treatment? As it happens, there is a noticeably
      wide range of responses to this matter in the various states of the United
      States, ranging from a strictly criminal perspective to one that does emphasize
      the importance of the mother's treatment. This diversity of dramatically
      different responses illustrates the failure to establish a uniform policy for the
      management of this phenomenon. Just as there is lack of consensus among those who
      favor punishment, the same lack of consensus characterizes those states espousing
      treatment. Several general policy recommendations are offered here addressing the
      critical issues. It is hoped that by focusing on these fundamental issues and
      ultimately detailing statistics, policymakers throughout the United States will
      consider the course of action that views both pregnant mother and fetus/child as
      humanely as possible.

PMID- 15169568
TI  - HIV CTL escape: at what cost?
AB  - Recent data have established the HIV-1 and SIV escape CTL through epitope
      mutation. However, three novel studies prove that such escape comes at a "cost"
      to overall viral fitness. Understanding how HIV-1/SIV escape CTL and the impact
      of the escape mutations has tremendous importance in developing CTL based
      vaccines. Further, a CTL based HIV-1 vaccine is likely to have long-term
      protective effect against disease only if the escape virus is significantly
      weakened compared with wild type.

PMID- 15169569
TI  - Two discrete events, human T-cell leukemia virus type I Tax oncoprotein
      expression and a separate stress stimulus, are required for induction of
      apoptosis in T-cells.
AB  - BACKGROUND: It is poorly understood why many transforming proteins reportedly
      enhance both cell growth (transformation) and cell death (apoptosis). At first
      glance, the ability to transform and the ability to engender apoptosis seem to be
      contradictory. Interestingly, both abilities have been widely reported in the
      literature for the HTLV-I Tax protein. RESULTS: To reconcile these apparently
      divergent findings, we sought to understand how Tax might cause apoptosis in a
      Jurkat T-cell line, JPX-9. Tax expression can be induced equally by either
      cadmium (Cd) or zinc (Zn) in JPX-9 cells. Surprisingly, when induced by Zn, but
      not when induced by Cd, Tax-expression produced significant apoptosis. Under our
      experimental conditions, Zn but not Cd, induced SAPK (stress activated protein
      kinase)/JNK (Jun kinase) activation in cells. We further showed that transient
      over-expression of Tax-alone or Jun-alone did not induce cell death. On the other
      hand, co-expression of Tax plus Jun did effectively result in apoptosis.
      CONCLUSION: We propose that Tax-expression alone in a T-cell background
      insufficiently accounts for apoptosis. On the other hand, Tax plus activation of
      a stress kinase can induce cell death. Thus, HTLV-I infection/transformation of
      cells requires two discrete events (i.e. oncoprotein expression and stress) to
      produce apoptosis.

PMID- 15169573
TI  - Role of antioxidants in treatment of male infertility: an overview of the
      literature.
AB  - Seminal oxidative stress in the male reproductive tract is known to result in
      peroxidative damage of the sperm plasma membrane and loss of its DNA integrity.
      Normally, a balance exists between concentrations of reactive oxygen species and
      antioxidant scavenging systems. One of the rational strategies to counteract the
      oxidative stress is to increase the scavenging capacity of seminal plasma.
      Numerous studies have evaluated the efficacy of antioxidants in male infertility.
      In this review, the results of different studies conducted have been analysed,
      and the evidence available to date is provided. It was found that although many
      clinical trials have demonstrated the beneficial effects of antioxidants in
      selected cases of male infertility, some studies failed to demonstrate the same
      benefit. The majority of the studies suffer from a lack of placebo-controlled,
      double-blind design, making it difficult to reach a definite conclusion. In
      addition, investigators have used different antioxidants in different
      combinations and dosages for varying durations. Pregnancy, the most relevant
      outcome parameter of fertility, was reported in only a few studies. Most studies
      failed to examine the effect of antioxidants on a specific group of infertile
      patients with high oxidative stress. Multicentre, double-blind studies with
      statistically accepted sample size are still needed to provide conclusive
      evidence on the benefit of antioxidants as a treatment modality for patients with
      male infertility.

PMID- 15169567
TI  - Early steps of retrovirus replicative cycle.
AB  - During the last two decades, the profusion of HIV research due to the urge to
      identify new therapeutic targets has led to a wealth of information on the
      retroviral replication cycle. However, while the late stages of the retrovirus
      life cycle, consisting of virus replication and egress, have been partly
      unraveled, the early steps remain largely enigmatic. These early steps consist of
      a long and perilous journey from the cell surface to the nucleus where the
      proviral DNA integrates into the host genome. Retroviral particles must bind
      specifically to their target cells, cross the plasma membrane, reverse-transcribe
      their RNA genome, while uncoating the cores, find their way to the nuclear
      membrane and penetrate into the nucleus to finally dock and integrate into the
      cellular genome. Along this journey, retroviruses hijack the cellular machinery,
      while at the same time counteracting cellular defenses. Elucidating these
      mechanisms and identifying which cellular factors are exploited by the
      retroviruses and which hinder their life cycle, will certainly lead to the
      discovery of new ways to inhibit viral replication and to improve retroviral
      vectors for gene transfer. Finally, as proven by many examples in the past,
      progresses in retrovirology will undoubtedly also provide some priceless insights
      into cell biology.

PMID- 15169575
TI  - Knocking-out genes controlling polarities in mice.

PMID- 15169576
TI  - Effects of recombinant LH supplementation in women undergoing assisted
      reproduction with GnRH agonist down-regulation and stimulation with recombinant
      FSH: an opening study.
AB  - Circulating endogenous concentrations of LH are reduced in women undergoing down
      regulation with gonadotrophin-releasing hormone agonists (GnRHa) and ovarian
      stimulation with recombinant human FSH (r-hFSH). The effect of recombinant human
      LH (r-hLH) supplementation on ovarian response and pregnancy outcome was
      evaluated in a prospective randomized study (sealed envelopes) including 231
      cycles. Normogonadotrophic women were stimulated with either r-hFSH or a
      combination of r-hFSH and r-hLH in a ratio of 2:1. LH supplementation was started
      from day 8 of the cycle. Blood samples for oestradiol, LH and androstendione were
      prospectively collected on days 1, 8 and on the day of aspiration and analysed
      retrospectively. Overall, the two groups did not differ with respect to pregnancy
      rate. In contrast, women aged > or =35 years responded to exogenous LH
      supplementation with significantly increased implantation rates and significantly
      reduced total FSH consumption as compared with the non-supplemented group. In
      addition, the implantation rate for a subgroup of patients with the highest
      endogenous LH concentrations (i.e. > or =1.99 IU/l) on day 8 was significantly
      increased by LH supplementation. Exogenous LH supplementation from day 8 has no
      detrimental effect on ovarian response and pregnancy outcome. On the contrary
      supplementation with r-hLH seems to benefit treatment outcome for women above 35
      years of age and for the subgroup of women exhibiting LH concentrations above
      1.99 IU/l on stimulation day 8.

PMID- 15169570
TI  - The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected
      cells.
AB  - BACKGROUND: The human T-cell leukemia virus type 1 (HTLV-1) Tax protein
      indirectly influences transcriptional activation, signal transduction, cell cycle
      control, and apoptosis. The function of Tax primarily relies on protein-protein
      interactions. We have previously shown that Tax upregulates the cell cycle
      checkpoint proteins p21/waf1 and cyclin D2. Here we describe the consequences of
      upregulating these G1/S checkpoint regulators in HTLV-1 infected cells. RESULTS:
      To further decipher any physical and functional interactions between cyclin D2
      and p21/waf1, we used a series of biochemical assays from HTLV-1 infected and
      uninfected cells. Immunoprecipitations from HTLV-1 infected cells showed p21/waf1
      in a stable complex with cyclin D2/cdk4. This complex is active as it
      phosphorylates the Rb protein in kinase assays. Confocal fluorescent microscopy
      indicated that p21/waf1 and cyclin D2 colocalize in HTLV-1 infected, but not in
      uninfected cells. Furthermore, in vitro kinase assays using purified proteins
      demonstrated that the addition of p21/waf1 to cyclin D2/cdk4 increased the kinase
      activity of cdk4. CONCLUSION: These data suggest that the p21/cyclin D2/cdk4
      complex is not an inhibitory complex and that p21/waf1 could potentially function
      as an assembly factor for the cyclin D2/cdk4 complex in HTLV-1 infected cells. A
      by-product of this assembly with cyclin D2/cdk4 is the sequestration of p21/waf1
      away from the cyclin E/cdk2 complex, allowing this active cyclin-cdk complex to
      phosphorylate Rb pocket proteins efficiently and push cells through the G1/S
      checkpoint. These two distinct functional and physical activities of p21/waf1
      suggest that RNA tumor viruses manipulate the G1/S checkpoint by deregulating
      cyclin and cdk complexes.

PMID- 15169577
TI  - Mouse parthenogenetic offspring from two mothers.

PMID- 15169578
TI  - PCOS: a diagnostic challenge.
AB  - Useful research and diagnostic criteria for PCOS arose from a conference in 1990,
      whereby PCOS could be defined by: (i) clinical and/or biochemical
      hyperandrogenism, (ii) chronic anovulation, and (iii) exclusion of related
      disorders. The presence of "polycystic ovaries" was not included in this
      definition, which created significant concern since many women with PCOS have
      polycystic ovaries on ultrasound, and conversely women with this ovarian
      morphology have a higher prevalence of androgen excess and insulin resistance.
      More recently, at an expert meeting in 2003 in Rotterdam, it was recommended that
      PCOS be defined when at least two of the following three features were present,
      after exclusion of other aetiologies: (i) oligo- or anovulation, (ii) clinical
      and/or biochemical hyperandrogenism, or (iii) polycystic ovaries. These newer
      criteria effectively create additional phenotypes of PCOS (e.g. women with
      hyperandrogenism and polycystic ovaries but normal ovulatory function, and women
      with ovulatory dysfunction and polycystic ovaries but no clinical or biochemical
      evidence of hyperandrogenism). It remains to be demonstrated whether these
      phenotypes actually represent patients with PCOS. Nonetheless, the trend towards
      the use of uniform diagnostic criteria in studies of PCOS will increase the
      comparability and potentially the value of published research.

PMID- 15169574
TI  - Administration of increasing amounts of gonadotrophin compromises preimplantation
      development of parthenogenetic mouse embryos.
AB  - The aim of the present study was to examine the effect of ovarian stimulation
      with increasing amounts of pregnant mare's serum gonadotrophin (PMSG) on
      preimplantation development of diploid parthenogenetic embryos in vitro.
      Administration of 5, 10 and 20 IU PMSG significantly increased the number of
      oocytes obtained per mouse in a dose-dependent manner. The amount of PMSG
      administered did not alter the proportion of degenerate oocytes. However, there
      was a significant decrease in the proportion of 8-cell/compacted embryos after 53
      h of culture with the administration of increasing amounts of PMSG. Proportion of
      embryos reaching at the blastocyst stage after 79 h of culture was reduced
      significantly in both the 10 and 20 IU PMSG groups. Reduced blastocyst
      development after 96 h of culture, however, was significant only in the 20 IU
      PMSG group. Total blastocyst, trophectoderm and inner cell mass numbers were also
      reduced significantly with the administration of 20 IU PMSG. It is concluded on
      the basis of these observations that preimplantation development of diploid
      parthenogenetic oocytes, which depends virtually entirely on maternal molecules
      accumulated during oogenesis along with gene products derived from the maternal
      genome, is compromised with the administration of increasing amounts of PMSG.

PMID- 15169579
TI  - Final report of the US President's Council on Bioethics and Assisted Conception.

PMID- 15169571
TI  - A murine leukemia virus with Cre-LoxP excisible coding sequences allowing
      superinfection, transgene delivery, and generation of host genomic deletions.
AB  - BACKGROUND: To generate a replication-competent retrovirus that could be
      conditionally inactivated, we flanked the viral genes of the Akv murine leukemia
      virus with LoxP sites. This provirus can delete its envelope gene by LoxP/Cre
      mediated recombination and thereby allow superinfection of Cre recombinase
      expressing cells. RESULTS: In our studies, the virus repeatedly infected the cell
      and delivered multiple copies of the viral genome to the host genome; the
      superinfected cells expressed a viral transgene on average twenty times more than
      non-superinfected cells. The insertion of multiple LoxP sites into the cellular
      genome also led to genomic deletions, as demonstrated by comparative genome
      hybridization. CONCLUSION: We envision that this technology may be particularly
      valuable for delivering transgenes and/or causing deletions.

PMID- 15169580
TI  - Assessment of glucose intolerance and insulin sensitivity in polycystic ovary
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with increased risk of impaired
      glucose tolerance and type 2 diabetes. PCOS has been considered as a major risk
      factor for the development of diabetes, and screening of women with PCOS for
      glucose intolerance is suggested. Detection of glucose intolerance in PCOS is
      best performed via 2-h oral glucose tolerance test rather than fasting plasma
      glucose alone, since it enables diagnosis of both impaired glucose tolerance and
      diabetes. Insulin resistance is a prominent feature of PCOS, although not all
      women with PCOS have insulin resistance. Measurement of insulin resistance is not
      included in the diagnostic criteria of the syndrome, and not required for the
      selection of treatments in current clinical practice. However, this measurement
      is undoubtedly of great interest for clinical research studies of PCOS. Several
      methods are available to the clinical investigator for the measurement of insulin
      resistance, yet there is no universally accepted and clinically useful
      definition, and no specific guidelines about how to measure it. While
      hyperinsulinaemic glucose clamp is considered to be the 'gold standard' for the
      measurement of insulin resistance, several alternative methods have been
      validated against the gold standard. Each method has its own merits and
      disadvantages. The choice of method for a particular study should be based on the
      specific aims, size, and type of that study. Variability in measurement of
      insulin resistance due to physiological factors, assay-related problems, and
      protocol differences in dynamic function tests deserves much more emphasis when
      interpreting the results of a study, or making comparisons between studies.

PMID- 15169581
TI  - Percutaneous epididymal sperm aspiration: a diagnostic tool for the prediction of
      complete spermatogenesis.
AB  - The classification of azoospermia into obstructive or non-obstructive is largely
      based on medical history, physical examination and biochemical markers in serum
      and semen. However, the most accurate parameter for diagnosis is the testicular
      histology. The predictive value of the percutaneous epididymal sperm aspiration
      (PESA), FSH, LH, testosterone, inhibin-B and testicular volume was investigated
      for their accuracy to predict a complete spermatogenesis (Johnsen score > or =8)
      in order to replace the testicular histology. The specificity and sensitivity of
      FSH, inhibin-B, LH, testosterone, testicular volume, and the presence of sperm in
      a PESA procedure was evaluated in 147 azoospermic males attending the centre for
      infertility diagnosis. A positive PESA outcome presented the highest sensitivity
      and specificity to predict a Johnsen score > or =8 (93 and 94% respectively)
      compared with FSH (90 and 19%), inhibin-B (88 and 57%) and testicular volume (95
      and 45%). Differences in clinical presentation were observed between patients
      with positive sperm retrieval with PESA, depending on the aetiology of
      obstruction. In conclusion, the presence of spermatozoa in the epididymis (PESA+)
      correlates with a Johnsen score > or =8 and is the most accurate parameter to
      predict complete spermatogenesis compared with clinical or biochemical
      parameters. Between obstructive azoospermic patients, the clinical parameters
      observed varied according to the aetiology.

PMID- 15169582
TI  - Haemopoietic embryo stem cells from a non-human primate.

PMID- 15169583
TI  - Spindle organization after cryopreservation of mouse, human, and bovine oocytes.
AB  - Oocyte cryopreservation would alleviate a number of ethical, social, and
      religious problems associated with human embryo storage. One potential problem is
      the effect of cryopreservation on the metaphase II spindle and chromosomes. The
      microtubules that make up the spindle tend to depolymerize at sub-physiological
      temperatures. Although there are numerous reports in the literature on this
      topic, discrepancies as to whether the spindle can or cannot reform persist. One
      of the confounding factors may be the low cryosurvival rates (around 50%) for
      mammalian oocytes. In recent years, a cryopreservation medium and protocol have
      been developed that allow oocytes of several species to be cryopreserved with
      high survival rates (>85%). Bovine, mouse, and human oocytes consistently
      reformed a morphologically normal spindle with chromosomes aligned along the
      metaphase plate (70% or higher) after first surviving cryopreservation (>87%
      survival for all species tested). Normal chromosome numbers were found in every
      second polar body tested by FISH (second polar bodies n = 4). It is concluded
      that the mammalian spindle, although depolymerized during cryopreservation, has
      the ability to reform, and in the mouse has been shown to function normally.
      Therefore, spindle reformation may not be a major cause for concern when storing
      mammalian MII oocytes.

PMID- 15169585
TI  - Heart grafts are becoming more common.

PMID- 15169584
TI  - Action of hypoxanthine and meiosis-activating sterol on oocyte maturation in the
      mouse is strain specific.
AB  - Follicular fluid meiosis-activating sterol (FF-MAS) is regarded as an important
      compound relevant to meiotic resumption in mammalian oocytes. The objective of
      this study was to investigate the influence of FF-MAS on germinal vesicle
      breakdown (GVBD) and first polar body (PBI) extrusion with regard to culture
      conditions, state of the oocyte and mouse strain. Denuded oocytes (DO) and
      cumulus-enclosed oocytes (CEO) were retrieved from PMSG-primed Quackenbush or
      C57BL/6J x DBA/2 (C57) mice and cultured for 20 h in alpha-MEM medium under the
      following conditions: (i) 250 micromol/l dibutyryl cAMP (dbcAMP) +/- EGF, 1 ng/ml
      or FF-MAS, 20 micromol/l; (ii) 4 mmol/l hypoxanthine (HX) +/- EGF or FF-MAS;
      (iii) HX + EGF + FF-MAS; and (iv) HX + FF-MAS 5 h priming and subsequent culture
      with HX + EGF. Oocyte GVBD and PBI emission were recorded and stained with
      Hoechst 33342. Very limited meiotic inhibition was observed in Quackenbush mice
      in comparison with C57 mice. FF-MAS promoted maturation in C57 DO and CEO and
      Quackenbush DO. In Quackenbush DO and CEO and C57 DO a significant increase in
      atypical PBI extrusion occurred, but not in C57 CEO as well as in EGF-treated
      Quackenbush CEO primed or co-cultured with FF-MAS. These results support a
      meiosis resumption function for FF-MAS and suggest that in its presence, the
      quality of the MII oocytes retrieved appears to be influenced by the strain of
      the mice, the state of the oocyte and the presence or absence of growth factors
      in the culture medium.

PMID- 15169586
TI  - Impact of oocyte pre-incubation time on fertilization, embryo quality and
      pregnancy rate after intracytoplasmic sperm injection.
AB  - Although, it is well known that pre-incubation of oocytes prior to conventional
      IVF improves fertilization and pregnancy rates, there are conflicting results
      regarding the effect of pre-incubation time in ICSI. This study evaluated the
      role of pre-incubation of oocytes on outcome in intracytoplasmic sperm injection
      (ICSI) cycles. A total of 1260 patients undergoing their first ICSI cycles were
      evaluated retrospectively. In patients undergoing ICSI during the year 2000
      (Group I, n = 670), oocytes were injected immediately after retrieval, whereas in
      patients undergoing ICSI during 2001 (Group II, n = 590), oocytes were incubated
      for 2-4 h prior to injection. The mean age of patients was 33.9 +/- 5.04 years
      and 34.1 +/- 5.06 years in groups I and II, respectively. The number of oocytes
      with a first polar body (MII) and fertilization and cleavage rates were higher,
      and embryo quality was significantly better in group II. In contrast, the total
      numbers of oocytes without a first polar body (MI), those where germinal vesicle
      breakdown had not occurred (GV), and empty zona oocytes were higher in group I.
      No difference was found in the number of embryos transferred or implantation or
      clinical pregnancy rates. This study demonstrated that pre-incubation of oocytes
      prior to ICSI is associated with improved maturation of oocytes, fertilization
      and embryo quality.

PMID- 15169587
TI  - Developmental capacity of different morphological types of day 5 human morulae
      and blastocysts.
AB  - After prolonged culture of human embryos, the expanded blastocysts with oval
      inner cell mass (ICM) and cohesive trophectoderm (TE) are preferably selected for
      transfer. In cycles with poor embryonic development, the selection has to be done
      from among suboptimal blastocysts for which no grading system exists. In this
      study, 1396 transferred blastocysts and morulae were classified into eight
      morphologic categories. The B1 category constituted the optimal blastocysts. The
      other categories were characterized by different deviations from optimal
      blastocysts: cytoplasmic fragments and necrosis in TE (B2), unexpanded
      blastocoele (B3), non-compact or small ICM (B4), fragments in TE and ICM (B5), up
      to 20% excluded blastomeres (B6), necrotic TE and ICM (B7), and more than 20%
      excluded cells from blastocysts (B8). The live birth rate was calculated from
      blastocysts with known outcome after transfer (88.9% transferred blastocysts).
      The birth rate declined from B1 to B8 by the same order and was: 45.2, 32.8,
      26.9, 23, 17.7, 16.7, 7.7 and 1.2% respectively. Normal ICM was recognized as the
      most important parameter for implantation. There was a strong relation between
      such ordered morphology categories and implantation capacity (P < 0.0001). Such a
      grading system is helpful in selecting the best of all available day-5 embryos
      for transfer.

PMID- 15169588
TI  - Pronuclear morphology predicts embryo development and chromosome constitution.
AB  - The relationship between pronuclear morphology on the one hand, and embryo
      development and chromosomal status on the other, was evaluated in 68 couples
      scheduled to undergo preimplantation genetic diagnosis because of advanced
      maternal age or recurrent implantation failure. Zygotes were grouped according to
      their pronuclear (PN) morphology. During the period from fertilization to embryo
      transfer, cleavage rate, embryo quality, blastocyst formation and results of the
      chromosomal analysis of 240 embryos were recorded. Both embryo cleavage
      characteristics and chromosome constitution were related to PN morphology.
      Embryos developing from zygotes with the normal PN pattern (pattern 0) cleaved
      faster and formed embryos with better morphology as compared with zygotes with
      abnormal PN patterns. Aneuploidy rate of embryos derived from zygotes with the
      normal PN pattern, with a single PN anomaly and with a double PN anomaly was
      25.6, 73 and 83% respectively. Chromosomally normal embryos with the normal PN
      pattern progressed to the blastocyst stage at a higher rate (90%) than
      chromosomally normal embryos with a single (61%) or a double (40%) PN anomaly.
      The same relationship applied to chromosomally abnormal embryos. It is concluded
      that PN morphology predicts both the risk of embryo developmental arrest and that
      of chromosomal abnormalities.

PMID- 15169589
TI  - Investigation of chromosomal imbalance in human embryos using comparative genomic
      hybridization.
AB  - Studies of cleavage-stage human embryos using fluorescence in-situ hybridization
      (FISH) to identify sub-sets of chromosomes have indicated that the incidence of
      chromosomal abnormalities is high. Whole genome amplification (WGA) and
      comparative genomic hybridization (CGH) to investigate the full chromosome
      complement applied to a small number of human embryos suggested an even higher
      rate of abnormality. WGA and CGH were used to identify genomic imbalance in
      individual blastomeres from human embryos, and the results were correlated with
      FISH analysis of sibling blastomeres. Forty embryos were analysed; 17 (42.5%) had
      a normal diploid karyotype and 23 (57.5%) were abnormal, with a chromosome
      imbalance in one or more cells including three (7.5%) that had a chaotic
      chromosome complement. Of the abnormal embryos, only three showed consistent
      aneuploidy. FISH results obtained from sibling blastomeres were in agreement with
      the CGH results in all 22 of the embryos where both tests were informative. It is
      concluded that rates of meiotic aneuploidy in human embryos may be lower than
      previous estimates. The results indicate that chromosomally abnormal embryos were
      more likely to have arisen as a result of cultural artefact or inadequate cell
      cycle surveillance, rather than meiotic error.

PMID- 15169590
TI  - In-vivo concentrations of inhibins, activin A and follistatin in human early
      pregnancy.
AB  - The aims of this study were to investigate the relationship between inhibins,
      activin A and follistatin in first trimester fetal fluids, maternal serum,
      placenta and decidua, and to investigate if these hormones are present in the
      circulation of the early second trimester human fetus. Amniotic and coelomic
      fluid, maternal serum, placental villi and decidual tissue were obtained from
      normal pregnancies at 8-12 weeks. Fetal blood by cardiocentesis and maternal
      blood were collected at 14-16 weeks gestation. Placental extracts had higher
      concentrations of inhibins, activin A and follistatin compared with decidual
      extracts. In the second trimester, inhibins and follistatin were detectable in
      fetal blood at 14-16 weeks gestation. Maternal serum concentrations of inhibin A
      (P < 0.001) and follistatin (P < 0.05) were significantly higher than fetal serum
      whereas inhibin B (P < 0.01) and pro-alpha C concentrations (P < 0.001) were
      higher in fetal serum. Inhibin B concentrations were also higher in male fetal
      serum samples that had higher concentrations of testosterone. The presence of all
      molecular forms of inhibins, activin A and follistatin in the first trimester
      fetal fluids, placental and decidual extracts in the first trimester confirms
      other reports. In the second trimester, high concentrations of inhibin B with
      testosterone in the fetal circulation indicate that these hormones may interact
      in the development of the male fetal gonads.

PMID- 15169591
TI  - Live delivery rates in subfertile women with Asherman's syndrome after
      hysteroscopic adhesiolysis using the resectoscope or the Versapoint system.
AB  - The purpose of this study was to report on a 10-year experience in the treatment
      of subfertile women with intrauterine adhesions using the resectoscope or the
      Versapoint system. Forty-six subfertile women with stage I (n = 6), stage II (n =
      25) and stage III (n = 15) intrauterine adhesions underwent adhesiolysis with the
      use of the resectoscope (n = 21) or the Versapoint system (n = 26). Synechiolysis
      was successful in 43 women (93.5%) after the first attempt. In 13 out of 14 women
      (92.9%) with oligo/amenorrhoea at presentation, restoration of menses was
      reported after adhesiolysis (Versapoint: 9/9, resectoscope: 4/5). Overall live
      delivery rates according to stage of intrauterine adhesions were 33.3, 44.4 and
      46.7% for stages I, II and III respectively. Similar cumulative delivery rates
      were achieved in patients with no additional infertility factors who attempted to
      conceive naturally after adhesiolysis using the Versapoint (71.7%) or the
      resectoscope (60%). Ten gestations ended in preterm delivery (50%), while in two
      of the women who delivered, a hysterectomy was performed due to placenta accreta.
      In conclusion, hysteroscopic adhesiolysis offers a real chance of parenthood in a
      substantial proportion of infertile couples either by using the Versapoint system
      or the resectoscope.

PMID- 15169592
TI  - Cdc42 and the fundamental control of polarity.

PMID- 15169593
TI  - Hysteroscopy only after recurrent IVF failure?

PMID- 15169594
TI  - Together or apart?

PMID- 15169595
TI  - What effect does classroom separation have on twins' behavior, progress at
      school, and reading abilities?
AB  - We investigated the effects of classroom separation on twins' behavior, progress
      at school, and reading abilities. This investigation was part of a longitudinal
      study of a nationally-representative sample of twins (the E-risk Study) who were
      assessed at the start of school (age 5) and followed up (age 7). We examined
      three groups of twins: pairs who were in the same class at both ages; pairs who
      were in separate classes at both ages; and pairs who were in the same class at
      age 5, but separated by age 7. When compared to those not separated, those
      separated early had significantly more teacher-rated internalizing problems and
      those separated later showed more internalizing problems and lower reading
      scores. Monozygotic (MZ) twins showed more problems as a result of separation
      than dizygotic (DZ) twins. No group differences emerged for externalizing
      problems, ADHD or prosocial behaviors. The implications of the findings for
      parents and teachers of twins, and for school practices about separating twins,
      are discussed.

PMID- 15169596
TI  - The first successful separation of conjoined twins (1689).
AB  - Reports on the first successful separation of conjoined twins in 1689 and
      especially the publication of this achievement, as late as 1752, in the
      Helvetisch-vernunftiche Wehe-Mutter by Johannes Fatio are discussed in this paper
      with the intention to correct several historical inaccuracies.

PMID- 15169597
TI  - Influence of socioeconomic levels on birthweight of twins and singletons.
AB  - This study aimed to compare birthweight distribution of twins and singletons from
      three different socioeconomic level hospitals and evaluate the possible
      contribution of assisted reproduction technologies (ART). Data for twins and
      singletons were collected in the 1990s from hospitals A (370 twins, 370
      singletons), B (306 twins, 306 singletons), and C (562 twins, 562 singletons).
      Only hospitals B and C have ART procedures. Gestational age was significantly
      lower in hospital C for singletons and twins. Birthweight for singletons was
      lower at hospital A (p <.005 for hospital B and p =.000 for hospital C); however,
      birthweight for twins was lower for hospitals A and C compared to hospital B (p
      =.000 for both comparisons). There were no differences between the mean
      birthweight for singletons and twins either to primigravidae or multigravidae in
      hospital A; nevertheless, for B and C the mean birthweight of twins was
      significantly lower in primigravidae than in multigravidae (p =.029 and p =.006,
      respectively). Considering twins up to 37-weeks of gestational age, hospital C
      showed the highest percentage of twin births (73.3%). These data suggest that the
      use of ART accounts for a disproportionate number of low birthweight and/or
      premature infants in primigravidae of higher socioeconomic level.

PMID- 15169598
TI  - Identifying a cohort of US twins using Social Security Administration records.
AB  - A sample of pairs of twins who were born in the United States in 1919 and
      survived to adulthood is identified through an innovative and large-scale
      application of the methodology of probabilistic linkage. The social security
      program began in the United States in November 1936, and the file of applicants
      for a social security number - which was used in this study - is the closest
      thing in the United States to a population register. The study results are very
      satisfactory, and demonstrate the superiority of probabilistic linkage to exact
      linkage. We estimate that about 33,000 twin pairs were born in the United States
      in 1919 and about 19,000 survived to age 17. Since the social security number was
      not then, at the inception of the program, the universal identifier that it is
      today, the number of enumerated twin pairs is somewhat less. Nonetheless, over
      16,000 twin pairs can be identified by the method of probabilistic linkage. By
      comparison, only about half as many can be identified by straightforward exact
      linkage.

PMID- 15169599
TI  - A longitudinal genetic analysis of low verbal and nonverbal cognitive abilities
      in early childhood.
AB  - By middle childhood, the same genetic factors are largely responsible for
      individual differences in verbal and nonverbal abilities, suggesting a genetic
      basis for general cognitive ability ("g"). Our previous work on verbal and
      nonverbal abilities throughout the normal range of variation during infancy and
      early childhood suggests that genetic influences show domain-specific as well as
      domain-general effects, implying that the switch to nearly complete domain
      general effects occurs later in development. Much less is known about the genetic
      structure of low cognitive performance, although our previous work has shown that
      a composite measure of low "g" is highly heritable at 2, 3 and 4 years of age. We
      report the first multivariate, longitudinal analyses of low verbal and nonverbal
      cognitive abilities (defined as the lowest 10% of the distribution) at 2, 3 and 4
      years of age using data from 9026 pairs of UK twins assessed by their parents as
      part of the Twins Early Development Study (TEDS). Domain-general genetic
      influences increased significantly from 2 to 3 to 4 years. Although the
      phenotypic polychoric correlation between low verbal and low nonverbal ability
      was similar at 2, 3 and 4 years (.36,.43,.35), the genetic contribution to the
      phenotypic correlation increased dramatically (.37,.47,.76), with a corresponding
      decrease in the comorbid influence of shared environment (.61,.44,.35). We
      conclude that for low ability, as well as for normal variation in ability,
      genetic "g" emerges during early childhood but is not fully developed until
      middle childhood.

PMID- 15169600
TI  - The Western Australian Register of Childhood Multiples: effects of questionnaire
      design and follow-up protocol on response rates and representativeness.
AB  - Twin registers have been established worldwide to study the roles of genes and
      the environment in health and behaviour. While questionnaire surveys are thought
      to be the most cost-effective way of collecting large amounts of data, low
      response rates can result in response bias. Many different strategies have been
      proposed to maximise response rates. A register of all multiple births occurring
      in Western Australia (WA) from 1980 onwards has been established using
      probabilistic record linkage techniques. Families who had not experienced the
      death of one or more of their multiples were invited to participate in the
      Western Australian Twin Child Health (WATCH) study, which studied the genetic and
      environmental determinants of childhood asthma and atopy. Several questionnaire
      designs and follow-up methods were assessed. We have shown that it was feasible
      to use a population-based register of multiple births to contact families for a
      questionnaire study. Questionnaire length, mode of follow-up, the number of
      responses required and the of participants all seemed to affect response.

PMID- 15169601
TI  - Disentangling genetic, environmental, and rater effects on internalizing and
      externalizing problem behavior in 10-year-old twins.
AB  - Previous studies have emphasized the importance of rater issues in studying the
      etiology of variation in internalizing and externalizing problems in children.
      Earlier results indicate only moderate agreement between parents, and assume that
      parents assess a specific aspect of their child's behavior. In comparable samples
      of younger children, additive genetic effects are the main factor explaining
      individual differences in both internalizing and externalizing behavior. It is
      unknown whether this pattern of rater influences and variance decomposition will
      be consistent in older children. Child Behavior Checklists (Achenbach, 1991),
      completed by both parents, were collected in a sample of 2956 Dutch 10-year-old
      twin pairs. The etiology of individual differences in internalizing and
      externalizing syndromes was examined using a model that corrected for possible
      rater bias, rater-specific effects and unreliability. The best fitting model
      suggested that disagreement between the parents is not merely the result of
      unreliability and/or rater bias, but each parent also provides specific
      information from his/her own perspective on the child's behavior. Significant
      influences of additive genetic, shared environmental and unique environmental
      factors were found for internalizing and externalizing syndromes.

PMID- 15169602
TI  - A population based twin study of sex differences in depressive symptoms.
AB  - Depressive symptoms reflect depressed mood over a relatively short period of time
      and are measured using symptom checklists such as the SCL-90. There is some
      evidence that depressive symptoms are associated with major depression (MD),
      which is a clinically diagnosed psychiatric illness. Genetic studies of
      depressive symptomatology suggest a role for genetic factors as well as unique
      environmental influences. While epidemiological research suggests that depressive
      symptoms may be influenced by sex-specific factors, few genetically informative
      findings support this result entirely. We used data from male and female same sex
      and opposite-sex twin pairs to assess the extent to which genetic, shared and
      unique environmental factors influence depressive symptoms. Furthermore, we
      tested for the presence of qualitative and quantitative sex differences in
      depressive symptoms. Our results suggest that similar to other studies,
      depressive symptomatology is moderately heritable (31%) with no evidence for
      shared environmental factors. Our best fitting model suggests that there are no
      qualitative or quantitative sex differences in depressive symptoms. Our analyses
      suggest that while there may be mean differences in the levels of depressive
      symptoms across sexes, the genetic and environmental factors that predispose
      males and females to depressive symptoms are not different.

PMID- 15169603
TI  - The heritability of breast cancer: a Bayesian correlated frailty model applied to
      Swedish twins data.
AB  - The aim of this study was to investigate the role of genes and environment in
      susceptibility to breast cancer and to give an estimate of heritability in the
      propensity to develop the disease. To do this we applied an interdisciplinary
      approach, merging models developed in the field of demography and survival
      analysis - so-called frailty models - and models coming from quantitative
      genetics and epidemiology, namely genetic models. In our study, the inferential
      problem was solved in a Bayesian framework and the numerical work was carried out
      using MCMC methods. We used the special information coming from twin data,
      particularly breast cancer data, from the Swedish Twin Register. The application
      of a correlated log-normal frailty model leads to a very large estimate of the
      population heterogeneity (sigma = 6.7), and relatively small correlations between
      co-twins' frailties - around 0.3 for monozygotic and 0.1 for dizygotic twins.
      Comparing three different genetic models (an ACE, an AE and an ADE model), we
      furthermore concluded that genetic effects would explain globally almost 30% of
      the total variability of propensity to breast cancer. Environmental effects would
      be predominant in determining breast cancer susceptibility and these effects
      would be primarily individual-specific, that is, non-shared effects. Finally, a
      model which includes dominance genetic effects (ADE model) is preferred for
      genetic and statistical reasons.

PMID- 15169605
TI  - Using identity-by-descent information in affected sib pairs to increase the
      efficiency of genetic association studies.
AB  - The aim of this study was to determine whether identity-by-descent (IBD)
      information for affected sib pairs (ASPs) can be used to select a sample of cases
      for a genetic case-control study which will provide more power for detecting
      association with loci in a known linkage region. By modeling the expected
      frequency of the disease allele in ASPs showing IBD sharing of 0, 1, or 2
      alleles, and considering additive, recessive, and dominant disease models, we
      show that cases selected from IBD 2 families are best for this purpose, followed
      by those selected from IBD 1 families; least useful are cases selected from IBD 0
      families.

PMID- 15169604
TI  - A genome scan for eye color in 502 twin families: most variation is due to a QTL
      on chromosome 15q.
AB  - We have rated eye color on a 3-point scale (1 = blue/grey, 2 = hazel/green, 3 =
      brown) in 502 twin families and carried out a 5-10 cM genome scan (400-757
      markers). We analyzed eye color as a threshold trait and performed multipoint sib
      pair linkage analysis using variance components analysis in Mx. A lod of 19.2 was
      found at the marker D15S1002, less than 1 cM from OCA2, which has been previously
      implicated in eye color variation. We estimate that 74% of variance in eye color
      liability is due to this QTL and a further 18% due to polygenic effects. However,
      a large shoulder on this peak suggests that other loci affecting eye color may be
      telomeric of OCA2 and inflating the QTL estimate. No other peaks reached genome
      wide significance, although lods > 2 were seen on 5p and 14q and lods >1 were
      additionally seen on chromosomes 2, 3, 6, 7, 8, 9, 17 and 18. Most of these
      secondary peaks were reduced or eliminated when we repeated the scan as a two
      locus analysis with the 15q linkage included, although this does not necessarily
      exclude them as false positives. We also estimated the interaction between the
      15q QTL and the other marker locus but there was only minor evidence for additive
      x additive epistasis. Elaborating the analysis to the full two-locus model
      including non-additive main effects and interactions did not strengthen the
      evidence for epistasis. We conclude that most variation in eye color in Europeans
      is due to polymorphism in OCA2 but that there may be modifiers at several other
      loci.

PMID- 15169607
TI  - Simian virus-40 as a gene therapy vector.
AB  - Simian virus-40 (SV40), an icosahedral papovavirus, has recently been modified to
      serve as a gene delivery vector. Recombinant SV40 vectors (rSV40) are good
      candidates for gene transfer, as they display some unique features: SV40 is a
      well-known virus, nonreplicative vectors are easy-to-make, and can be produced in
      titers of 10(12) IU/ml. They also efficiently transduce both resting and dividing
      cells, deliver persistent transgene expression to a wide range of cell types, and
      are nonimmunogenic. Present disadvantages of rSV40 vectors for gene therapy are a
      small cloning capacity and the possible risks related to random integration of
      the viral genome into the host genome. Considerable efforts have been devoted to
      modifing this virus and setting up protocols for viral production. Preliminary
      therapeutic results obtained both in tissue culture cells and in animal models
      for heritable and acquired diseases indicate that rSV40 vectors are promising
      gene transfer vehicles. This article reviews the work performed with SV40 viruses
      as recombinant vectors for gene transfer. A summary of the structure, genomic
      organization, and life cycle of wild-type SV40 viruses is presented. Furthermore,
      the strategies utilized for the development, production, and titering of rSV40
      vectors are discussed. Last, the therapeutic applications developed to date are
      highlighted.

PMID- 15169608
TI  - Cardiovascular drugs inhibit MMP-9 activity from human THP-1 macrophages.
AB  - It is now recognized that atherosclerosis complications are related to the
      unstable character of the plaque rather than its volume. Vulnerable plaques often
      contain a large lipid core, a reduced content of smooth muscle cells, and
      accumulation of inflammatory cells. Colocalization of macrophages and active
      matrix metalloproteinases (MMPs) is likely relevant for atherosclerotic lesion
      disruption. Nevertheless, MMP activity and regulation by cardiovascular drugs
      remains poorly defined. In this study, we evaluated the effects of avasimibe,
      fluvastatin, and peroxisome proliferator-activated receptor (PPAR) ligands on 92
      kDa gelatinase B (MMP-9) secretion by human THP-1 macrophages. THP-1 macrophages
      were treated with compounds for 48 h, and secreted MMP-9 protein was quantified
      by immunoassay. Avasimibe, fluvastatin, and PPARalpha agonists (fenofibric acid
      and Wy-14643) significantly reduced, in a concentration-dependent manner, MMP-9
      protein (up to 67 +/- 5% for fenofibric acid). In these assays, the PPARgamma
      selective agonist rosiglitazone displayed a lower efficacy than other compounds.
      Enzymatic activity of MMP-9 was also decreased by all cardiovascular drugs
      tested. MMP-9 protein/activity inhibition by cardiovascular drugs was due, at
      least in part, to a decrease in MMP-9 mRNA. These results show that THP-1
      macrophages could be an useful cellular model to investigate effects of compounds
      on plaque vulnerability through MMP-9 activity.

PMID- 15169609
TI  - Presence of a human Hyaluronan binding protein 1 (HABP1) pseudogene-like sequence
      in Methanosarcina barkeri suggests its linkage in evolution.
AB  - The gene encoding Hyaluronan binding protein 1 (HABP1) and its homologs have been
      reported across eukaryotes, from yeast to human. We have reported the presence of
      processed pseudogenes in several human chromosomes, along with the location of
      the HABP1 gene on chromosome 17p12-p13. In this study, we report not only the
      presence of HABP1 pseudogene in other animal species, but also the presence of a
      homologous sequence in Methanosarcina barkeri, an ancient life form. This
      sequence has 44.8% homology to the human HABP1 cDNA and 45.3% homology with the
      HABP1 pseudogene in human chromosome 21. This sequence has a high G + C content
      (57%), characteristic of archaea, a family to which M. barkeri belongs. The
      presence of this HABP1 cDNA like fragment in M. barkeri might enable us to shed
      light on the evolution of the HABPl gene and whether it was present in a common
      ancestral organism before the lineages separated.

PMID- 15169610
TI  - Harbinger transposons and an ancient HARBI1 gene derived from a transposase.
AB  - In this study we report main properties of Harbinger DNA transposons identified
      in protists, plants, insects, worms, and vertebrates. This is the first
      superfamily of eukaryotic DNA transposons where all autonomous transposons, even
      those that are hosted by species from different kingdoms, encode two proteins: a
      superfamily-specific transposase and a DNA-binding protein characterized by the
      presence of the conserved SANT/myb/trihelix motif. The last motif is known to be
      important for the DNA binding by different transcription regulators. Therefore,
      we suggest that this protein is necessary for coordinated expression of the
      Harbinger transposase. Although mammalian genomes are free of recognizable
      remnants of Harbingers, we identified a widely expressed HARBI1 gene encoding a
      350-aa protein entirely derived from a Harbinger transposase some 450-500 million
      years ago. The HARBI1 proteins are conserved in humans, rats, mice, cows, pigs,
      chickens, frogs, and various bony fish, as well as other extremely important
      proteins, including RAG1 and RAG2. Conserved motifs detected in the Harbinger
      transposases are also well preserved in the HARBI1 proteins. Therefore, the
      HARBI1 proteins are expected to be nucleases important for functioning of bony
      vertebrates. We also found that the protein most similar to HARBI1 is encoded by
      an autonomous Harbinger 3_DR transposon that was transpositionally active in the
      zebrafish genome a few million years ago. Nonautonomous transposons derived from
      Harbinger3_DR are characterized by a striking preference for a 17-bp target site
      never seen previously in any other DNA transposon. Based on this observation, we
      suggest that the hypothetical HARBI1 nucleases are also characterized by a strong
      DNA-target specificity.

PMID- 15169611
TI  - Genomic and phylogenic comparisons of the alpha-globin and beta-globin intergenic
      sequences between zebra fish (Danio rerio) and six closely related Cyprinindae
      species.
AB  - The alpha-globin and beta-globin genes of the zebrafish are tightly linked on the
      same chromosome in a 3'-5' and 5'-3' configuration, respectively. Although the
      location of the controlling sequences has been mapped to the intergenic region,
      analysis determining the uniqueness of this unusual arrangement to zebrafish has
      not been undertaken. To explore this, we isolated, sequenced, and
      phylogenetically analyzed the intergenic region between globin gene families of
      seven Cyprinindae species including zebrafish. These species were grouped into an
      in group (immediate relatives, not so distant relatives), and an out group
      (distant relative). Cellulose acetate electrophoresis of hemoglobin (Hb) detected
      multiple variants in each species, but a band with electrophoretic mobility (EM)
      of 6.7 x 10(-5) cm(2).volt(-1).sec(-1) was shared between species. Polymerase
      chain reaction (PCR) amplification of the intergenic globin gene region also
      detected a 1.0-kb fragment that was repeated in the in group and a 1.2-kb
      fragment in the out group. Sequence comparison confirmed that the genetic
      orientation and controlling sequences location were conserved throughout this
      region in all seven species. This phylogenic footprinting indicated that the
      configuration was not exclusive to zebrafish. To confirm sequence alignment,
      maximum parsimony phylogenic analysis, was performed. Only one member of that
      group the giant danio, was not closely clustered, being located almost
      equidistance between the immediate relative and the species of the other
      clusters. This may represent an ancestral configuration prior to transposition of
      the alpha globin and beta-globin genes families to nonsynteny.

PMID- 15169612
TI  - The humoral and cellular immune responses in mice induced by DNA vaccine
      expressing the sporozoite surface protein of Cryptosporidium parvum.
AB  - Cryptosporidiosis, a protozoan disease, is caused by Cryptosporidium parvum in
      animals and humans. To study the humoral and cellular immune responses induced by
      DNA vaccine expressing the sporozoite surface protein, CP15/60, of
      Cryptosporidium parvum, the recombinant plasmid containing the CP15/60 gene was
      injected into tibialis a interior muscle of BALB/c mice. The mice were
      subsequently given booster doses twice at 3-week intervals. The humoral and
      cellular immune responses were detected at different times after immunization.
      The mice were then challenged by inoculation of 1 x 10(6) oocysts of C. parvum.
      The experimental results have shown that the recombinant plasmid can induce
      corresponding specific immune responses and thus protect the mice from challenge
      of the oocysts, suggesting that the recombinant plasmid could be a potential
      candidate of DNA vaccine.

PMID- 15169613
TI  - A test of integration of the activation hypothesis and the diathesis-stress
      component of the hopelessness theory of depression.
AB  - OBJECTIVES: This prospective study tested the integration of the diathesis-stress
      component of the hopelessness theory of depression (Abramson, Metalsky, & Alloy,
      1989) and Persons and Miranda's (1992) activation hypothesis (i.e. depressogenic
      inferential styles are typically latent cognitive processes that must be primed
      in order to be accurately assessed). DESIGN: In order to test the diathesis
      stress component of the hopelessness theory, we used a short-term longitudinal
      design. In order to test the activation hypothesis, inferential styles were
      assessed both before and after a negative cognitive priming questionnaire.
      METHODS: A group of 165 university students completed measures of inferential
      styles about the self, consequences, and causes before and after completing a
      negative cognitive priming questionnaire (Time 1). Participants also completed
      measures of depressive symptoms prior to completing the cognitive priming
      questionnaire and 5 weeks later (Time 2). Finally, negative events occurring
      between Time 1 and Time 2 were assessed. RESULTS: Contrary to the diathesis
      stress component of the hopelessness theory, none of the unprimed inferential
      styles interacted with negative events to predict increases in depressive
      symptoms. In line with the integration of the hopelessness theory and the
      activation hypothesis, however, each of the primed inferential styles interacted
      with negative events to predict increases in depressive symptoms even after
      controlling for the proportion of variance in depressive symptoms accounted for
      by the unprimed inferential style stress interactions. CONCLUSION: Individuals
      with depressogenic inferential styles are likely to show increases in depressive
      symptoms following the occurrence of negative events. At the same time, these
      depressogenic inferential styles are typically latent cognitive processes that
      must be primed in order to be accurately assessed.

PMID- 15169614
TI  - Rumination and future thinking in depression.
AB  - OBJECTIVES: Future thinking is an important domain of cognitive functioning, with
      reduced ability to imagine positive future events associated with hopelessness in
      depression and parasuicide. Rumination has been shown to exacerbate negative
      cognitive biases in depression, and to reduce likelihood estimations for positive
      future events. We examine the hypothesis that, in depressed patients, rumination
      would reduce the ability to imagine positive future events, whilst increasing the
      ability to imagine negative future events. METHOD: The ability to imagine
      positive and negative future events was assessed using the future thinking
      paradigm (MacLeod, Rose, & Williams, 1993). Depressed and nondepressed
      participants completed the future thinking task after being randomly allocated to
      either a rumination or distraction manipulation (Nolen-Hoeksema & Morrow, 1993).
      Mood was measured before and after the manipulation. Participants also completed
      a standard verbal fluency task. RESULTS: In the depressed group, compared to
      distraction, rumination increased both negative and positive future thinking,
      although the effect was only significant for negative future thinking once
      baseline levels of hopelessness were controlled for. These findings are
      consistent with the prediction that rumination would increase negative future
      thinking, but inconsistent with the prediction that rumination would reduce
      positive future thinking. Previous findings that, compared to controls, depressed
      patients generated fewer positive future events were replicated. CONCLUSION:
      Ruminative self-focus leads to greater negative future thinking in depressed
      patients, further confirming that rumination exacerbates negative cognitive
      biases in depression. The relationship between rumination and positive future
      thinking was unexpected, but might potentially reflect a general priming of self
      related information by rumination.

PMID- 15169615
TI  - The distress experienced by voice hearers is associated with the perceived
      relationship between the voice hearer and the voice.
AB  - OBJECTIVES: To explore the relationship between distress and the perceptions that
      voice hearers have of their relationship with the voice they hear. We predicted
      that a dominant style of relating by the voice and a submissive and distancing
      style of relating by the voice hearer would be linked with distress. METHOD:
      Thirty people who were hearing voices took part in the study. Information was
      gathered about the characteristics of the voice-hearing experience, the level of
      distress experienced in relation to the voice, the relationship between the voice
      hearer and the voice, and level of depression. RESULTS: The tendency for the
      voice to relate in a dominating, insulting manner and the tendency of individuals
      to react with suspicion and lack of communication with the voice were uniquely
      associated with distress. CONCLUSIONS: Appraisals of the relationship between the
      voice and voice hearer made by voice hearers are associated with differing
      emotional responses to voices. Clinical assessments of people who have
      distressing voices may be enhanced by a detailed consideration of the sort of
      relationship that exists between the client and their voice.

PMID- 15169616
TI  - The construction of awareness in early-stage Alzheimer's disease: a review of
      concepts and models.
AB  - OBJECTIVES: This review considers the concepts and models that, often implicitly,
      underlie accounts and studies of variations in awareness of difficulties in
      people with early-stage Alzheimer's disease (AD). In order to do this, it is
      necessary to draw on explanations presented within the discourses of different
      disciplines. The review aims to explore the key tensions and debates that arise
      in attempting to conceptualize awareness, and attempts to specify what kind of
      conceptual framework is needed in order to advance our understanding of
      variations in awareness in AD. METHODS: A range of literature relating to
      concepts and models of awareness, drawn from different disciplines and published
      during the past 30 years, is critically reviewed. RESULTS: The literatures of
      different disciplines present varying constructions of the concept of awareness.
      Neuropsychological, psychiatric and psychosocial explanations are considered and
      their relevance to understanding awareness in early-stage AD is discussed.
      CONCLUSIONS: An understanding of variations in awareness in early-stage AD
      requires a biopsychosocial model of awareness that incorporates the influence of
      both neuropsychological impairments and psychosocial responses. Improved
      understanding of variations in awareness is essential for the development of
      person-centred approaches to intervention and care in AD.

PMID- 15169617
TI  - Awareness in early-stage Alzheimer's disease: a review of methods and evidence.
AB  - PURPOSE: This review has three main aims: (1) To illustrate the strengths and
      limitations of current approaches to assessing awareness of difficulties and
      impairments in people with early-stage Alzheimer's disease (AD). (2) To consider
      the evidence regarding factors associated with level of awareness. (3) To
      highlight the implications for assessment and intervention. METHODS: A
      comprehensive range of literature on awareness in AD published in the past 20
      years is critically reviewed. RESULTS: Four main approaches to the assessment of
      awareness can be discerned, each with significant conceptual and methodological
      limitations. These limitations affect the quality of the available evidence
      regarding factors associated with level of awareness, which is contradictory,
      with few clear findings emerging. Awareness does, however, appear to be related
      to the outcome of rehabilitation, and this has important implications for the
      selection of appropriate and sensitive interventions. CONCLUSIONS: The review
      highlights the need for a broad conceptualization of awareness. Greater clarity
      about theoretical frameworks, and improved assessment methods, are required in
      order to enhance understanding of variations in awareness in early-stage AD.
      Awareness is an important variable for clinicians to consider.

PMID- 15169618
TI  - Monitoring cognitive changes: psychometric properties of six cognitive tests.
AB  - OBJECTIVES: Repeated neuropsychological assessments are often used to monitor
      change in cognitive functioning over time. Thus, knowledge about the reliability
      and stability of neuropsychological tests and the effects of age and IQ is of
      paramount importance. In this study we document, for six cognitive tests: test
      retest reliabilities, practice effects, reliable change (RC) indices corrected
      for practice, and the impact of premorbid IQ and age. DESIGN: A sample of 188
      normal adults (aged 40-70 years) were administered, on two occasions, one or more
      of the following tests: the Graded Naming Test (GNT), the Silhouettes Test, two
      tests of verbal fluency, the Modified Wisconsin Card Sorting Test, and a new test
      of speed and attention (the Symbol Digit Test). There was a 1-month interval
      between assessments. At first assessment, all participants were administered the
      revised National Adult Reading Test (NART). RESULTS: The test-retest reliability
      of the tests ranged from very good (the GNT and Silhouettes Test) to moderate
      (verbal fluency tests and Symbol Digit Test) and to poor (Modified Card Sorting
      Test). Significant, although modest, practice effects were found on all tests. RC
      indices were generally large except for the Graded Naming Test and the
      Silhouettes Test. Premorbid IQ scores significantly correlated with performance
      on all the tests, the exception being semantic fluency. Age only correlated with
      the Silhouettes Test and the new Symbol Digit Test. Neither NART IQ nor age
      correlated with practice effects. CONCLUSION: The psychometric properties of the
      GNT and Silhouettes Test indicated that they are useful tools for monitoring even
      small cognitive changes. In contrast, the verbal fluency tests and the new Symbol
      Digit Test are only suitable for monitoring large changes in performance. The
      Modified Card Sorting Test is an unreliable tool for monitoring 'executive'
      functions.

PMID- 15169620
TI  - Conformational flexibility of beta-secretase: molecular dynamics simulation and
      essential dynamics analysis.
AB  - AIM: Based on the structural analysis to reveal the mechanism of ligand binding
      to beta-secretase and the specificity of each binding sub-site. METHODS:
      Molecular dynamics was used to simulate on the ligand free beta-secretase and
      ligand bound beta-secretase. The trajectories were analyzed using the essential
      dynamics, and the significant conformational change was illustrated employing the
      DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly
      showed that the beta-secretase experienced a large conformational change upon the
      substrate or inhibitor binding. The flap structure adopted a swing motion,
      gradually covering the active site to facilitate the ligand binding process.
      Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction
      analysis revealed that residues at P2, P1, and P1' positions of the inhibitor
      were very important for the binding, and residues at P2' and P3' positions may be
      modified to improve the binding specificity. S3 subsite of the enzyme still had
      space to modify the inhibitors in increasing the binding affinity. CONCLUSION:
      The information presented here is valuable and could be used to identify small
      molecular inhibitors of beta-secretase.

PMID- 15169619
TI  - Reduced negative priming in schizotypy: failure to replicate.
AB  - OBJECTIVE: The aim of the present study was to investigate the association of
      negative priming and schizotypal personality using a Stroop-version of the
      paradigm. METHODS: Negative priming was determined for 160 healthy participants.
      Schizotypal symptoms were assessed with several schizotypal scales. RESULTS: No
      significant relationship emerged between any of the schizotypal scales and
      negative priming. CONCLUSIONS: It is inferred that negative priming is
      undisturbed in schizophrenia and schizotypy when unmasked negative priming tasks
      are employed. Reduced negative priming in previous studies may represent an epi
      phenomenon of short prime presentation times and backward masking.

PMID- 15169621
TI  - NMDA and AMPA receptors mediate intracellular calcium increase in rat cortical
      astrocytes.
AB  - AIM: To study the effect of glutamate on the intracellular calcium signal of pure
      cultured rat astrocytes and the role of N-methyl-D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in the
      procedure. METHODS: The fluorescence of calcium was measured by Fura-2/AM
      (F(345)/F(380)). RESULTS: L-Glutamate induced [Ca(2+)](i) increase in most of the
      cells in concentration- and time-dependent manner. NMDA 50 mmol/L induced the
      fluorescence increase by almost three to four times, while the effect of AMPA 50
      mmol/L was just half of that of D-(-)-2-amino-5-phosphonopentanoic acid (D-AP-5;
      a selective antagonist of the NMDA receptor). 6-Cyano-7-nitroquinoxaline-2,3
      dione (CNQX, a selective antagonist of the AMPA receptor) abolished the effects
      of NMDA and AMPA, respectively. D-AP-5 and CNQX simultaneously or respectively
      attenuated the effect of L-glutamate at different degrees, but could not abolish
      it entirely. CONCLUSION: Glutamate modulated intracellular Ca(2+) of pure
      cultured rat astrocytes through different pathways. The activation of NMDA and
      AMPA receptors took part in the complex mechanisms.

PMID- 15169624
TI  - Integrin beta4 mAb inhibited apoptosis induced by deprivation of growth factors
      in vascular endothelial cells.
AB  - AIM: To understand the mechanism by which anti-beta4 integrin monoclonal antibody
      (mAb) inhibits apoptosis of vascular endothelial cells (VEC). METHODS: Viability
      was determined by counting the cells that attached to dishes after treatments.
      DNA fragmentation was analyzed by agarose gel electrophoresis and fluorescence
      microscopy. The intracellular content of cAMP was measured by radioimmunoassay
      (RIA). The levels of p53 and Ras expressions were analyzed by fluorescence
      microscopy combined with immunofluorescence under laser scanning confocal
      microscopy. RESULTS: After the cells were deprived of fibroblast growth factor
      (FGF) and serum were exposed to the mAb 5 mg/L for 24 h, the detachment and DNA
      fragmentation of these cells were suppressed. When cells were deprived of FGF and
      serum, the intracellular cAMP level and Ras protein content decreased (P<0.05),
      while the level of p53 protein expression increased (P<0.05). But in the presence
      of anti-beta4 integrin mAb, VEC apoptosis was inhibited, and at the same time,
      the changes mentioned above were obviously blocked (P<0.05). CONCLUSION: Anti-4
      integrin mAb inhibited apoptosis by affecting the level of cAMP, and blocking
      down-regulation of Ras protein and up-regulation of p53 protein in VEC.

PMID- 15169623
TI  - Monosialoganglioside protected ischemic rat hippocampal slices through
      stabilizing expression of N-methyl-D-aspartate receptor subunit.
AB  - AIM: To determine direct protective effect of monosialoganglioside (GM1) on
      hippocampal slices after oxygen-glucose deprivation and reperfusion (OGD/RP), and
      investigate the influence on the expression of N-methyl-D-aspartate receptor
      subunit 1 (NMDAR1) in those hippocampal slices. METHODS: Injury of hippocampal
      slices and protective effects of GM1 were detected by 2,3,5-triphenyltetrazolium
      chloride (TTC) staining, toluidine blue staining, and transmission electron
      microscopy of rat hippocampal slices. Expression of NMDAR1 was detected by
      Western blot. RESULTS: (1) GM1 at 1.0 micromol/L was the most effective
      concentration to preserve the TTC staining of the hippocampal slices after OGD/RP
      (P<0.05), and the next was GM1 at 10.0 micromol/L (P<0.05). (2) Toluidine blue
      staining and transmission electron microscopy showed GM1 protected the injuried
      hippocamal slices after OGD/RP. (3) GM1 downregulated the temporally high
      expression of NMDAR1 in the hippocampal slices immediately after a 25-min OGD and
      prevented the over low expression of NMDAR1 after a 30-min reperfusion.
      CONCLUSION: GM1 could protect injuried rat hippocampal slices after OGD/RP
      through stabilizing the expression of NMDAR1.

PMID- 15169622
TI  - Direct transfer of A20 gene into pancreas protected mice from streptozotocin
      induced diabetes.
AB  - AIM: To investigate the efficiency of transfer of A20 gene into pancreas against
      STZ-induced diabetes. METHODS: PVP-plasmid mixture was directly transferred into
      the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3
      LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed
      by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20
      transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO
      generation, and histological examination were examined. RESULTS: Injection of PVP
      plasmid mixture directly into the pancreatic parenchyma increased urine amylase
      concentration 16 h after operation and reversed it to nearly normal 36 h later.
      On d 33 LacZ expression could be found in spleen, duodenum, and islets. The
      development of diabetes was prevented by direct A20 gene transferring into the
      pancreas and A20-mediated protection was correlated with suppression of NO
      production. The insulitis was ameliorated in A20-treated mice. CONCLUSION:
      Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to
      target gene expression in islets. Direct transfer of A20 gene into the pancreas
      protected mice from STZ-induced diabetes.

PMID- 15169626
TI  - An increase in opening of BK(Ca) channels in smooth muscle cells in
      streptozotocin-induced diabetic mice.
AB  - AIM: To investigate the changes of function of large conductance of calcium
      activated potassium channels (BK(Ca) channels) in thoracic aortic smooth muscle
      cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice.
      METHODS: Vascular muscle tension in the isolated thoracic aortic rings of mice
      was compared, and the role of BK(Ca) channels in relaxation of isolated mice
      thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile,
      single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and
      BK(Ca) currents were recorded by patch-clamp single channel recording technique
      in symmetric high potassium solution. RESULTS: Tetraethylammonium (TEA) 1 mmol/L,
      a selective calcium-activated potassium channel blocker, caused significant
      rightward shift in the concentration-response curves of ACh in the isolated
      thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation
      was decreased notably after TEA treatment [(6.3+/-0.4) vs (6.9+/-0.5), n=10 rings
      from 7 mice, P<0.01]. But pD2 value of ACh-induced relaxation in age-matched
      control mice did not change in presence and absence of TEA 1 mmol/L [(6.4+/-0.15)
      vs (6.5+/-0.5), n=7 rings from 6 mice, P>0.05]. Furthermore, conductance of
      BK(Ca) channels in single thoracic aortic smooth muscle cells was decreased
      [(199+/-15) pS, n=10 cells from 7 mice vs (266+/-11) pS, n=12 cells from 6 mice,
      P<0.01], but probability of open of BKCa channels was increased [(0.51+/-0.28) vs
      (0.11+/-0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in
      diabetic mice was reduced [(15+/-15) vs (132+/-98), n=6 cells from 6 mice,
      P<0.05]. CONCLUSION: The opening of BK(Ca) channels was increased in thoracic
      aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J
      mice by reducing mean closed time, but the conductance of BK(Ca) channels was
      decreased.

PMID- 15169625
TI  - Dispersion of ventricular mRNA of RyR2 and SERCA2 associated with
      arrhythmogenesis in rats.
AB  - AIM: To investigate the effect of CPU86017 on the changes of mRNA abundance of
      different calcium handling system in infarcted heart. METHODS: Rats were
      subjected to left coronary ligation to induce myocardial infarction (MI). The
      treatment with either propranolol (Pro) 5 mg/kg ip or CPU86017 1, 2, and 4 mg/kg
      ip was initiated on the next day of operation and continued for 20 d. Medication
      with isoproterenol (Isop) 3 mg/kg sc started on the d 17-21. Ventricular mRNA
      abundance of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+)-ATPase
      (SERCA2), L-type Ca(2+) channel, and Na(+)/Ca(2+)exchanger (NCX1) were measured.
      RESULTS: Arrhythmic scores (AS) in the Isop group was raised up to 5.27+/-1.75
      (P<0.01) vs myocardial infarction group 2.25+/-2.04 and sham group 1.50+/-1.73.
      The AS was depressed by Pro (1.63+/-1.53, P<0.01 vs Isop), and CPU86017 2 and 4
      mg/kg (3.00+/-1.24, and 1.70+/-1.85, P<0.01 vs Isop). The significant dispersion
      of depressed mRNA abundance of RyR2 and SERCA2 was associated with an increase in
      AS in Isop group, and it was much depressed in the left than the right ventricle.
      The dispersion and depression of mRNA were restored significantly by Pro and
      CPU86017, associated with suppression on AS. In Isop group, the mRNA abundance of
      L-type Ca(2+) channel was not changed; and a moderate increase in the mRNA of
      NCX1 was seen, the changes were regressed by Pro and CPU86017. CONCLUSION: Isop
      induced arrhythmogenesis in MI heart was correlated mainly with a dispersion of
      depressed mRNA abundance in ventricle likely due to the consequence of PKA over
      phosphorylation. A suppression of arrhythmia by Pro and CPU86017 resulted from a
      regression of the dispersion and depression of RyR2 and SERCA2.

PMID- 15169627
TI  - Decreases of voltage-dependent K+ currents densities in ventricular myocytes of
      guinea pigs by chronic oxidant stress.
AB  - AIM: To determine the changes of delayed rectifier K(+) currents (I(k)) and
      inward rectifier K(+) currents (I(k1)) in the ventricular myocytes of guinea pigs
      during the gradual apoptotic process by the chronic oxidant stress treatment.
      METHODS: H(2)O(2) 50 micromol/L (24 h) was used for inducing apoptosis in the
      cardiomyocytes culture of neonatal rats and to treat the isolated ventricular
      myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by TUNEL
      methods and voltage-dependent K(+) currents were recorded by patch-clamp
      techniques. RESULTS: H(2)O(2) 50 micromol/L (24 h) induced cell apoptosis in the
      cardiomyocytes culture of neonatal rats. This concentration was used to treat the
      isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the
      voltage-dependent K(+) currents densities (I(k), I(k1)) were down-regulated. The
      densities of the delayed rectifier K(+) currents (I(k)) in 50 micromol/L H(2)O(2)
      group were 2.52+/-0.57 pA/pF vs 5.73+/-1.84 pA/pF in the control group at +50 mV
      (n=8, P<0.01). The densities of the inward rectifier K(+) currents (I(k1)) in 50
      micromol/L H(2)O(2) group were -13.9+/-2.70 pA/pF, 2.52+/-0.57 pA/pF vs -59.7+/
      11.9 pA/pF, 5.73+/-1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and 
      40 mV (n=8, P<0.05), respectively. The extent of inward rectifier property of
      I(k1) was weakened by 50 micromol/L H(2)O(2) treatment. CONCLUSION: The densities
      of I(k), I(k1) in the cardiomyocytes of guinea pigs were down-regulated and the
      inward rectifier property of I(k1) was weakened during the gradual apoptotic
      process after 50 micromol/L H(2)O(2) treatment for 24 h.

PMID- 15169628
TI  - Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced
      cytotoxicity in human colon cancer cells.
AB  - AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle
      progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29
      cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution, protein
      level, and kinase activity were determined by clonogenic assay, flow cytometry,
      DNA synthesis assay, immunoblotting, and kinase assays, respectively. RESULTS:
      UCN-01 abrogated an S/G2-phase checkpoint in HT-29 cells treated with ara-C. When
      UCN-01 was added after treatment with ara-C, the rate of recovery of DNA
      synthesis was enhanced and colony-forming ability diminished. Thus, premature
      recovery of DNA synthesis was associated with increased cytotoxicity.
      Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities,
      Cdc25C phosphorylation, and Chk1 kinase activity were consistent with UCN-01
      induced abrogation of the S/G2-phase checkpoint in ara-C treated cells.
      CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of
      Chk1 kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was
      combined with ara-C suggested a rationale for the use of this drug combination
      for tumors that might be susceptible to cell cycle checkpoint abrogation.

PMID- 15169629
TI  - Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone
      spontaneously hypertensive rats.
AB  - AIM: To elucidate the cardioprotective effects of T-type calcium channel blocker
      mibefradil and compare with that of the angiotensin-converting enzyme inhibitor
      ramipril in a stroke-prone spontaneously hypertensive rats (SHR-SP) model of
      congestive heart failure (CHF) after myocardial infarction (MI). METHODS: SHR-SP
      rats were subjected to permanent ligation of the left anterior decending coronary
      artery. Treatment with mibefradil (10 mg.kg(-1).d(-1)), ramipril (10 mg.kg(-1).d(
      1)), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks
      after induction of MI. Sham-operated rats served as controls. RESULTS: In placebo
      treated MI rats, six weeks after MI, left ventricular circumference, inner
      diameter, and left ventricular end-diastolic pressure (LVEDP) were increased,
      whereas mean arterial blood pressure (MAP) and maximum rate of rise of left
      ventricular pressure (dp/dt(max)) were decreased compared with sham-operated
      controls (P<0.01). In ramipril-treated MI rats, heart weight, heart weight to
      body weight ratio and interstitial collagen content were reduced (P<0.05,
      P<0.01), LVEDP was slightly decreased (P>0.05), and dp/dt(max) was improved
      (P<0.01) compared with placebo-treated MI rats. In contrast, in mibefradil
      treated MI rats, heart weight, heart weight to body weight ratio were slightly
      but not significantly reduced, LVEDP was slightly elevated compared with placebo
      treated MI rats, and was elevated (P<0.05) compared with ramipril-treated MI
      rats, although interstitial collagen content were reduced (P<0.01) compared with
      placebo-treated MI rats. CONCLUSION: Chronic treatment with ramipril diminishes
      cardiac remodeling of heart failure after MI to a greater extent than mibefradil.
      Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in
      LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil
      might be deleterious rather than beneficial compared with ramipril or even
      placebo treatment in experimental MI.

PMID- 15169630
TI  - General gambogic acids inhibited growth of human hepatoma SMMC-7721 cells in
      vitro and in nude mice.
AB  - AIM: To study the inhibitory effect of general gambogic acids (GGA) on
      transplantation tumor SMMC-7721 in experimental animal model and SMMC-7721 cells
      in vitro. METHODS: Anti-tumor activity of GGA in the experimental transplantation
      tumor SMMC-7721 was evaluated by relative tumor growth ratio. Cell morphology was
      observed with inverted microscope and electron microscope. Cell proliferation was
      measured by MTT assay and the telomerase activity was determined by PCR. RESULTS:
      In vivo study indicated that GGA (2, 4, and 8 mg/kg, iv, 3 times per week for 3
      weeks) displayed an inhibitory effect on the growth of transplantation tumor SMMC
      7721 in nude mice compared with the normal saline group (P<0.01). At the
      concentrations of 0.625-5.0 mg/L, GGA remarkably inhibited the proliferation of
      SMMC-7721 cells in vitro. GGA 2 mg/L dramatically changed morphology of SMMC-7721
      cells and inhibited the telomerase activity in SMMC-7721 cells. CONCLUSION: GGA
      had inhibitory effect on the growth of SMMC-7721, which might be related to its
      inhibition of telomerase activity.

PMID- 15169631
TI  - A high-throughput model for screening anti-tumor agents capable of promoting
      polymerization of tubulin in vitro.
AB  - AIM: To establish a high-throughput model for screening anti-tumor agents capable
      of promoting the polymerization of tubulin in vitro. METHODS: Tubulin was
      prepared in different purity for two screening steps. The first step was a high
      throughput screening (HTS) for a set of 1500 samples using the GTP-containing
      tubulin and the end-reading method. The second step was performed on 119 hits
      from the first screening by a kinetic assay with GTP-lacking tubulin. RESULTS:
      The HTS for 1500 samples was accomplished in less than 3 h. From the screening,
      108 samples were identified with >20 % promotion activity at 10 mg/L. Five of 108
      were further confirmed by the kinetic assay using the purified tubulin
      subsequently. Three of the hit compounds were Epothilone A or its analogs, the
      other two compounds had new structures with a common pharmacophore for cytotoxic
      natural products that stabilize microtubules. In an MTT test, the five selected
      samples from the screening showed a minimal IC(50) at 0.28+/-0.06 nmol/L to Hela
      cells. CONCLUSION: The two-step screening method is a high-throughtput, cost
      effective, and efficient approach to identify microtubule-stabilizing agents.

PMID- 15169632
TI  - Recombinant fibronectin polypeptide antagonizes hepatic failure induced by
      endotoxin in mice.
AB  - AIM: To study the preventive effect of recombinant human fibronectin (rhFN)
      polypeptide on hepatic failure induced by endotoxin in mice. METHODS: A cDNA
      fragment coding for Ile1363-Tyr1725 of human FN was inserted into the PinPoint Xa
      3 plasmid, and the constructed plasmid was transformed into E coli BL21 (DE3)
      cells, and then the expression of rhFN polypeptide in DE3 cells was identified
      through SDS-PAGE. The target protein from the supernatant of bacteria lysate was
      purified through biotin-affinity chromatography. The bioactivity of the purified
      rhFN polypeptide was determined with cell adhesive activity. The survival rate
      was observed in endotoxemia mice injected with rhFN polypeptide. The tissue
      damage in hepatocyte was detected using histology, ultrastructure, and DNA
      fragmentation assay. RESULTS: The expression of rhFN polypeptide reached
      approximately 20 % of the total cellular protein. The adhesion ability of rhFN
      polypeptide was concentration-dependent. The value of EC(50) was 0.8 nmol/L. The
      survival rate of endotoxemia mice sensitized by D-galactosamine (D-GalN) was 60 %
      in rhFN polypeptide treated group, while that of endotoxemia mice sensitized by D
      GalN was 20 % in the control group (P<0.01). Histopathology showed that less
      necrosis occurred on the hepatocyte of endotoxemia mice injected with rhFN
      polypeptide compared with saline control. Ultrastructure and DNA fragmentation
      assay showed that no apoptotic hepatocyte was observed in the liver of rhFN
      treated endotoxemia mice. CONCLUSION: Recombinant fibronectin polypeptide
      antagonizes hepatic failure induced by endotoxin in mice.

PMID- 15169633
TI  - Efficient delivery of human clotting factor IX after injection of lentiviral
      vectors in utero.
AB  - AIM: To explore gene transfer feasibility for human clotting factor IX (hFIX)
      mediated by recombinant lentivirus in utero. METHODS: ICR mice fetus at 17-19 d
      gestation were received lentiviral vectors carrying hFIX cDNA under the control
      of liver specific promoter by intrahepatic injection. The expression and
      distribution of hFIX cDNA and possible immune responses against the hFIX were
      assessed by ELISA, PCR, RT-PCR, and immunohistochemistry, respectively. RESULTS:
      The serum hFIX protein were detected at different time points in all newborn
      mice, the highest level of hFIX was 50 microg/L and lasted for more than 30 d.
      Anti-hFIX antibody was not detected. hFIX cDNA was detected in liver, spleen, and
      heart. The expression of hFIX cDNA was only detected in liver. Besides, no germ
      line transmission was found at DNA and RNA levels, and no side effect associated
      with gene transfer was detected. CONCLUSION: The efficient delivery of hFIX can
      be achieved by prenatal gene transfer. It thus shows the feasibility of gene
      therapy for hemophilia in utero.

PMID- 15169635
TI  - Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in
      monkey plasma.
AB  - AIM: To establish the method for quantitation of the phosphorothioate
      oligodeoxynucleotides (S-ODNs) in plasma. METHODS: Two solid-phase extraction
      columns combined with a strong anion-exchange column were utilized to remove
      proteins and lipids in plasma, and the salts were removed by a reverse-phase
      column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of
      the tested S-ODNs, PS20, and its metabolites extracted from the plasma were
      determined by the method of non-gel sieving capillary electrophoresis (NGCE) with
      diode array detection in the presence of internal standard (IS). RESULTS: The
      method was with good base number specificity. Relative standard deviation % of
      both intra and inter assay were all less than 10 %, and the total mean recovery
      was about 91 %. The methodology was successfully used to determine the PK
      behavior of an anti-tumor antisense S-ODNs in monkeys and identify the
      metabolites with single base difference. CONCLUSION: The combined method of solid
      phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs,
      and the main parameters of the methodology met the requirement of PK study.

PMID- 15169634
TI  - Production of human liver prolidase by Saccharomyces cerevisiae as host cells.
AB  - AIM: To clone and express the recombinant human liver prolidase in yeast and
      explore the activities of both dipeptidase and organophosphoric acid anhydrolase
      (OPAA). METHODS: The cDNA encoding human liver prolidase derived from healthy
      adult liver was cloned into the pYES2, an expression vector of S cerevisiae, and
      then transformed into S cerevisiae INVSc1 by electroporation. The transformant
      with the highest enzymatic activity was induced by galactose for expression. The
      optimal induction conditions (temperature, induction time, and the initial amount
      of inoculation cells) were estimated by orthogonal experimental design. The
      recombinant prolidase and OPAA activities were assayed by spectrocolorimetric
      methods. RESULTS: The recombinant enzyme catalyzed the hydrolysis of
      organophosphorous compound soman as well as the hydrolysis of dipeptide Gly-Pro.
      Under the optimal induction conditions (20 h, 25 degree, initial OD(600)=0.4),
      the maximum activities of prolidase and OPAA came to 226.5 and 578 micromol.min(
      1).g(-1) protein in cell lysate supernatants, respectively. SDS-PAGE of the
      recombinant enzyme in disrupted cell supernatants showed a molecular weight of 56
      kDa. Intensity scanning of the SDS-PAGE gel revealed that the enzyme accounted
      for 3.16 % of the total protein in the supernatant. One liter incubation medium
      produced 7 g of wet yeast cell containing 4.56 mg of the recombination protein.
      CONCLUSION: The recombinant human liver prolidase produced by yeast cell (S
      cerevisiae) exhibited both dipeptidase and OPAA activities.

PMID- 15169636
TI  - Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization
      with active chromatin.
AB  - AIM: To establish an animal model for systemic lupus erythematosus (SLE)-like
      syndrome in mice. METHODS: BALB/c mice were immunized with active chromatin
      isolated from ConA-activated syngeneic spleno-lymphocytes. Plasma samples of mice
      were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG
      anti-dsDNA, -ssDNA, and anti-histone antibodies. Tumor necrosis factor-alpha (TNF
      alpha) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and
      the levels of interferon-gamma (IFN-gamma) in supernatants were tested
      respectively. Proteinuria was measured. Kidneys were examined by direct
      immunohistochemical method and light microscopy. RESULTS: Anti-ds DNA, ssDNA, and
      histone antibodies were induced in active chromatin-immunized mice, the
      proliferation response of splenocytes to ConA and LPS were reduced, levels of
      interferon-gamma in supernatants and TNF-alpha in serum were lowered. Lupus
      nephritis was assessed by the presence of Ig deposits, glomerular pathology and
      proteinuria. CONCLUSION: The active chromatin-induced SLE-like mouse model was
      similar to idiopathic SLE in human.

PMID- 15169637
TI  - Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis.
AB  - AIM: To study effects of acetazolamide on aquaporin-1 (AQP(1)) protein expression
      and angiogenesis. METHODS: Establishing Lewis-lung-carcinoma model, the
      localization of AQP(1) in tumor tissues was investigated by immunohistochemical
      methods; The biological activity of acetazolamide was detected by endothelial
      cells proliferation test (MTT) assay and chorioallantoic membrane (CAM) vascular
      inhibition test. RESULTS: Immunohistochemical localization of AQP(1) in mice
      tumor was labeled in capillaries, post capillary venules endothelial cells. After
      being treated with acetazolamide, the number of capillaries and post capillary
      venules was significantly decreased in tumor tissue. Acetazolamide showed
      significant inhibitory effect on angiogenesis in CAM and endothelial cell
      proliferation. CONCLUSION: Acetazolamide might be identified and developed as one
      of potential lead compounds for a new therapeutic intervention in inhibiting
      cancer angiogenesis.

PMID- 15169638
TI  - Effects of esculentoside A on production of interleukin-1, 2, and prostaglandin
      E2.
AB  - AIM: To investigate the influence of esculentoside A (EsA) on immunological
      function and its mechanism of anti-inflammation. METHODS: Interleukin-1
      production was measured by thymocyte co-stimulating assay; the radioactivity of
      [(3)H]arachidonic acid (AA) was used to evaluate the release of AA; prostaglandin
      E2 production was measured with radioimmunoassay (RIA); IL-2 and IFN-gamma were
      detected by ELISA method. RESULTS: EsA (3-12 micromol/L)could potently inhibit
      the production of IL-1 and PGE(2) from both silent and LPS induced macrophages.
      EsA had no significant effect on the release of AA from murine macrophages. EsA
      could inhibit the production of IL-2 from murine lymphocytes induced by ConA, but
      not affect the production from silent lymphocytes. EsA showed no effect on the
      production of IFN-gamma from both silent and ConA induced lymphocytes.
      CONCLUSION: EsA could affect the immunological function through inhibiting the
      production of IL-2 from activated splenocytes and the inhibition of production of
      IL-1 and PGE(2) might be one of the anti-inflammation mechanisms of EsA.

PMID- 15169639
TI  - Inhibition of histamine release from human mast cells by natural chymase
      inhibitors.
AB  - AIM: To investigate the ability of natural chymase inhibitors to modulate
      histamine release from human mast cells. METHODS: Enzymatically dispersed cells
      from human lung, tonsil, and skin were challenged with anti-IgE or calcium
      ionophore A23187 in the absence or presence of the natural chymase inhibitors
      secretory leukocyte protease inhibitor (SLPI) and alpha(1)-antitrypsin, then
      histamine release was determined. RESULTS: IgE-dependent histamine release from
      lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61 %, and 62 %,
      respectively following incubation with alpha(1)-antitrypsin (5000 nmol/L). SLPI
      5000 nmol/L was also able to inhibit anti-IgE-dependent histamine released from
      lung, tonsil and skin mast cells by up to approximately 72 %, 67 %, and 58 %,
      respectively. While neither alpha(1)-antitrypsin nor SLPI by themselves altered
      histamine release from lung, tonsil and skin mast cells, they were able to
      inhibit calcium ionophore-induced histamine release from lung and tonsil mast
      cells. CONCLUSION: Both micro(1)-antitrypsin and SLPI could potently inhibit IgE
      dependent and calcium ionophore- induced histamine release from dispersed human
      lung, tonsil, and skin mast cells in a concentration-dependent manner, which
      suggested that they were likely to play a protective role in mast cell associated
      diseases including allergy.

PMID- 15169640
TI  - Stimulation of mucin secretion from human bronchial epithelial cells by mast cell
      chymase.
AB  - AIM: To investigate the effect of chymase on the mucin secretion from human
      bronchial epithelial cells. METHODS: Primarily-cultured human bronchial
      epithelial (PCHBE) cells and normal human bronchial epithelial (NHBE) cells were
      cultured with chymase or other stimulus in a mixture of bronchial epithelial
      growth medium (BEGM) and Dulbecco's modified Eagle's medium (DMEM), and the
      quantities of stimulatory mucin release were recorded. MUC5AC mucin was measured
      with an ELISA and dolichos biflorus agglutinin (DBA) mucin was determined with an
      enzyme linked DBA assay. RESULTS: A dose-dependent secretion of DBA mucin from
      PCHBE cells was observed with chymase with a maximum secretion of 98 % above
      baseline being achieved following 3 h incubation. The action of chymase started
      from 1 h, peaked at 3 h and dramatically decreased at 20 h following incubation.
      Chymase was able to also stimulate approximately 38 % increase in MUC5AC mucin
      release from PCHBE cells, and about 121 % increase in DBA mucin release from NHBE
      cells. A chymase inhibitor soybean trypsin inhibitor (SBTI) was able to inhibit
      up to 85 % chymase induced mucin release, indicating that the enzymatic activity
      was essential for the actions of chymase on bronchial epithelial cells.
      CONCLUSION: Chymase is a potent stimulus of mucin secretion from human bronchial
      epithelial cells. It can contribute to mucus hypersecretion process in the
      patients with chronic obstructive pulmonary disease or asthma.

PMID- 15169642
TI  - Cure of experimental botulism and antibotulismic effect of toosendanin.
AB  - Botulinum neurotoxins (BoNTs), a group of bacterial proteins that comprise a
      light chain disulfide linked a heavy chain, are the most lethal biotoxins known
      to mankind. By inhibiting neurotransmitter release, BoNTs cause severe
      neuroparalytic disease, botulism. A series of important findings in the past 10
      years which displayed the molecular targets of BoNTs and hence proposed a four
      step action mechanism to explain BoNT intoxication greatly advanced the study of
      antibotulismic drug. In this article, we reviewed these progresses and anti
      botulismic compounds found in recent years. These compounds function due to their
      facilitation on neurotransmitter release or to their interference on the binding,
      internalization, translocation, and endopeptidase activity of the toxins.
      Toosendanin is a triterpenoid derivative extracted from a digestive tract
      parasiticide in Chinese traditional medicine. Chinese scientists have found that
      the compound is a selective prejunctional blocker. In spite of sharing some
      similar action with BoNT, toosendanin can protect botulism animals that have been
      administrated with lethal doses of BoNT/A or BoNT/B for several hours from death
      and make them restore normal activity. The neuromuscular junction preparations
      isolated from the rats that have been injected with toosendanin tolerate BoNT/A
      challenge. Toosendanin seems to have no effect on endopeptidase activity of BoNT,
      but blocks the toxin approach to its enzymatic substrate.

PMID- 15169641
TI  - Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides
      peptide.
AB  - AIM: To investigate the antitumor and anti-angiogenic activity of Ganoderma
      lucidum polysaccharides peptide (GLPP). METHODS: Antitumor effect of GLPP was
      observed in tumor-bearing mice in vivo. At the same time, the effects of GLPP on
      proliferation of tumor cells and human umbilical cord vascular endothelial cell
      (HUVEC) were detected by MTT assay in vitro. Subsequently, spleen lymphocytes
      proliferation of nude mice was stimulated by LPS or ConA. To investigate the anti
      angiogenic effect of GLPP, GLPP 80 microg per disc and GLPP-treated serum 10
      microL per disc were added to the chick chorioallantoic membrane (CAM)
      respectively in vivo. RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of
      Sarcoma 180 in BALB/c mice markedly by 35.2 %, 45.2 %, and 61.9 %, respectively.
      GLPP which was directly added to the cultured medium did not inhibit PG cell
      proliferation in vitro; but GLPP-treated serum 50, 100, 200 mg/kg potently
      inhibited PG cell proliferation by 22.5 %, 26.8 %, and 30.3 %, respectively; and
      reduced the xenograft (human lung carcinoma cell PG) in BALB/c nude mice greatly
      in vivo by 55.5 %, 46.0 %, and 46.8 %, respectively. Lymphocytes proliferation of
      nude mice could be stimulated by LPS 5 mg/L but not by ConA 2.5 mg/L, indicating
      that GLPP could not promote the T lymphocyte proliferation and neutral red
      phagocytosis of peritoneal macrophages of nude mice. The CAM assay showed that
      GLPP and GLPP-treated serum had anti-angiogenic effect. GLPP (1, 10, and 100
      mg/L) inhibited HUVEC proliferation in vitro with the inhibitory rate of 9.4 %,
      15.6 %, and 40.4 %, respectively. CONCLUSION: GLPP has antitumor and anti
      angiogenic activity. The anti-angiogenesis of GLPP may be a new mechanism
      underlying its anti-tumor effects.

PMID- 15169643
TI  - [Construction of mutants of MHC class II molecule transactivator gene capable of
      suppressing HLA-DR/DQ expression and exploration on their mechanism].
AB  - AIM: To construct MHC class II transactivator (CIITA) gene mutants which could
      suppress the expression of MHC class II molecule and explore its mechanism.
      METHODS: Restrictive enzymes digestion, PCR and synthesized oligonucleotide
      strands were used to construct three mutants including pcDNA3mCIITA2,
      pcDNA3mCIITA3 and pcDNA3mCIITA4. These mutants and pcDNA3 vector were transfected
      into Hela and Raji cell lines by lipofectamine. RT-PCR and flow cytometry were
      used to determine the changes of the inducible/constitutive expression of MHC
      class II-molecule. The mCIITA4 mutant was transferred to the tetracycline dose
      dependent plasmid pUHD10-3. By adjusting the concentration of Dox in cultural
      circumstances, and regulating expressed level of external mutant C II TA, the
      relationship between the expression level of mC II TA4 mutant and that of MHC
      class II molecule was observed. RESULTS: pcDNA3mCIITA3 and pcDNA3mCIITA4 could
      significantly suppress the expression of HLA-DR/DQ gene in Hela and Raji cells,
      while pcDNA3 empty vector and pcDNA3mCIITA2 had no effect on the MHC class II
      expression. The inhibition rate of MHC class II molecule expression was directly
      proportional to the quantity of transfected CII TA mutant. CONCLUSION: The
      mutants pcDNA3 mCII TA3 and pcDNA3mCIITA4 can suppress the expression of MHC
      class II gene. Above date confirmed primarily that mutant C II TA suppressed the
      expression of MHC class II molecule by competitive binding with transactivator
      for the normal endogenous wild type C II TA molecule.

PMID- 15169644
TI  - [Inhibition of intracellular Ca(2+)-chelating agent on Hela cell apoptosis
      induced by HSV-1].
AB  - AIM: To explore the variation of intracellular free-Ca (2+) concentration during
      Hela cell apoptosis induced by HSV-1 and inhibition of Ca(2+)-chelating agent on
      the apoptosis. METHODS: Apoptosis of the Hela cells infected by HSV-1 was
      observed under scanning electron microscope (SEM) and transmission electron
      microscope (TEM), and the variation of intracellular free-Ca (2+) concentration,
      labeled with fluorescent probe was observed under fluorescence-microscope at a
      series of timepoints. RESULTS: The Hela cells infected by HSV-1 showed typical
      apoptotic morphological changes. Free-Ca (2+) concentration increased and reached
      peak at the 12 hours after HSV-1 infection. Characteristic morphological features
      of apoptosis occurred at the 24 hours after infection. This apoptosis could be
      inhibited by intracellular Ca(2+)-chelating agent. CONCLUSION: Intracellular free
      Ca(2+) might play an important role in Hela cell apoptosis induced by HSV-1,
      which provides useful clues for clinical treatment of associated diseases.

PMID- 15169645
TI  - [In-vivo dynamic changes of antigen presenting cells infected with recombinant
      attenuated Salmonella typhimurium expressing green fluorescent protein].
AB  - AIM: To clarify in-vivo early dynamic changes of antigen-presenting cells (APCs)
      infected with recombinant attenuated Salmonella typhimurium. METHODS: BALB/c mice
      were orally infected with recombinant attenuated Salmonella typhimurium
      expressing green fluorescent protein (GFP) X4550 (pYAGFP). Peritoneal macrophages
      were taken out 3 days after infection, cultured for 24 hours, and observed under
      the fluorescent microscope. Moreover, BALB/c mice were also infected
      intravenously with X4550 (pYAGFP) and low density cells (LDCs) were isolated and
      prepared from mouse spleen and liver 3,6 and 12 hours after infection. Infection
      rates of macrophages and dendritic cells (DCs) were analyzed by flow cytometry.
      RESULTS: About 50% peritoneal macrophages were X4550 (pYAGFP) positive. Infection
      rates of macrophages in spleen and liver were about 20%-40%. As for the DCs, the
      infection rates in spleen and liver were about 4%-10% and 10%-20%, respectively.
      CONCLUSION: Recombinant attenuated Salmonella can be captured by APCs in-vivo in
      early infection, which provides a precondition for inducing effective immune
      responses.

PMID- 15169646
TI  - [Change of activity of NF-kappaB p65 in lymphocytes from rats with oral tolerance
      induced by Fx1A].
AB  - AIM: To explore the activity change and significance of NF-kappaB p65 in
      lymphocytes from rats with oral tolerance induced by Fx1A. METHODS: 30 female
      Wistar rats were divided into two groups (oral tolerance and control groups),
      which stomachs were perfused with Fx1A and PBS, respectively. The delayed-type
      hypersensitivity (DTH) was evaluated by skin test, the immune function was
      detected by splenic lymphocyte proliferation test, the activity of NF-kappaB p65
      and expression of TGF-beta1 in lymphoid tissues were examined by
      immunohistochemical staining and Sandwich ELISA. RESULTS: In comparison with
      control group, the DTH and antigen-specific lymphocyte proliferation reaction in
      oral tolerance group were suppressed significantly. The activity of NF-kappaB p65
      and expression of TGF-beta1 in Peyer's patch were increased notably. However, the
      activity of NF-kappaB p65 was decreased, but expression of TGF-beta1 was
      increased markedly in splenic lymphocytes. CONCLUSION: Information of oral
      tolerance induced by Fx1A may be related to the change of NF-kappaB p65 activity
      in lymphocytes of body's different places.

PMID- 15169647
TI  - [The expression of 5 immune molecules on rat peripheral leucocytes after heart
      transplantation].
AB  - AIM: To observe 5 kinds of immune molecule expressions on rat peripheral
      leucocytes at varying time points after ectopic heart transplantation and explore
      the mechanism of acute rejection reaction. METHODS: Donor's heart derived from SD
      rat was transplanted into the abdomen cavity of Wistar rat by anastomosis of
      donor's aorta and pulmonary artery to recipient's abdominal aorta and inferior
      venacava for establishing coronary perfusion. Before and after transplantation,
      peripheral leucocytes were isolated from venous blood and labelled with the
      monoclonal antibodies(mAbs) against CD4, CD8, IL-2R, ICAM-I and MHC-II molecules,
      respectively. The these molecule levels were assessed by flowcytometry.
      Simultaneity, graft's pathological changes and their survival rate were observed.
      RESULTS: At 24 hours after transplantation, MHC-II molecule expression was
      increased, while expressions of CD4, IL-2R and ICAM-I were significantly
      decreased, but CD8 expression had no change. At 72 hours after operation, the
      expressions of CD4, CD8 and IL-2R increased and expressions of CD8 and IL-2R
      reached to peak. At 7-10 days after operation, except that CD4 expression
      increased continuously, the expressions of 4 other molecules decreased gradually.
      The survival rate of graft at varying times after operation were 100%( 24 h),
      85.7%(3 days), 16.7%(7 days) and, 0 (10 and 12 days), respectively. Pathological
      examination showed that there was no notable pathological change in cardiac
      muscle tissue. At the third day after operation, 4 out of 7 transplanted hearts
      had only grade I A pathological change. Grade II and above grade II pathological
      changes were observed in all 6 grafts at the 7th day after operation. CONCLUSION:
      These data indicate that graft rejection reaction begin to appear in first 72
      hours, and effector phase of the reaction appear mainly within 3-7 days after
      heart transplantation.

PMID- 15169648
TI  - [Construction and expression of recombinant antibody/granzyme B containing
      truncated translocating peptide].
AB  - AIM: To construct an eukaryotic expression vector for recombinant
      antibody/granzyme B gene containing truncated translocating peptide and express
      it in HER-2(+) SKBR-3 cells and HER-2(-) Hela cells. METHODS: PCR amplication was
      used to obtain recombinant DNA encoding antibody/granzyme B containing truncated
      translocating peptide DNA, and then the DNA fragment was cloned into eukaryotic
      expression vector pCMV-e23sFv-PE40. After being transfected into SKBR-3 cells and
      Hela cells, the expression of target gene and its effect on cellular morphology
      were detected by immunocytochemical staining. RESULTS: The eukaryotic expression
      vector encoding recombinant antibody/granzyme B containing truncated
      translocating peptide was successfully constructed. e23sFv-FSD-GrB protein was
      expressed in most of Hela cells and had no effect on Hela cells, but the
      transfected SKBR-3 cells which also express e23sFv-FSD-GrB protein exhibited
      condensed nucleus and cytoplasm. CONCLUSION: The construction of eukaryotic
      expression vector of recombinant antibody/granzyme B gene containing truncated
      translocating peptide lays the foundation for further determination of minimal
      fragment responsible for translocation.

PMID- 15169649
TI  - [Construction,identification and amplification of a yeast two-hybrid random cycle
      peptide library].
AB  - AIM: To construct a cycle peptide library composed of 16 random amino acids with
      yeast two-hybrid system. METHODS: Random oligonucleotides encoding 16-mer
      peptides were designed and synthesized artificially, and then were amplified by
      PCR. The amplified products were digested with BamH I and EcoR I and cloned into
      yeast expression plasmid pGADT(7) GH to construct the cycle library plasmids
      pGADT(7) GH-RP Then the number of different recombinants and the randomness of
      the library were tested, and the cycle peptide library plasmids were amplified,
      extracted and purified. RESULTS: A random cycle peptide library with 1.28 x10(7)
      different recombinant clones was obtained. No significant difference was found
      between amino acid distribution in the cycle peptide library and the expected
      frequency. CONCLUSION: The random cycle peptide library has been successfully
      constructed. And a lot of cycle peptide library plasmids with high purity were
      obtained.

PMID- 15169650
TI  - [Construction and identification of recombinant adenovirus vector containing
      thioredoxin reductase gene].
AB  - AIM: To construct recombinant adenovirus vector containing human thioredoxin
      reductase (TR) gene and to explore the correlation between antioxidant activity
      of TR and the degenerative neuropathy. METHODS: Full length TR cDNA was obtained
      from recombinant plasmid pGEM-TR via digestion with Apa I and Not I and was
      cloned into pShuttle vector and pShuttle-TR was recut with I-Ceu I and PI-Sce I.
      Fragment containing TR gene and CMV promoter was inserted into E1 and E3
      deficient adeno-X virus DNA, and then the recombinant adenovirus vector was
      transfected into HEK 293 cells through lipofectamine and identified by PCR. The
      TR expression on and in cell lysate of CV1 cells infected with recombinant
      adenovirus was by immuno fluorescence assay and Western blot analysis. RESULTS:
      After replication of recombinant adenovirus Adeno-TR, the virus titer was about
      4.4x10(11) pfu/L. The TR expression on CV1 cells was proved by fluorescent
      microscopy. Western blot analysis showed a band with relative molecular mass
      (M(r)) of 55,000. CONCLUSION: A recombinant adenovirus vector has been
      successfully constructed and TR is expressed on CV1 cells. This result lays the
      foundation for further study on function of TR and its correlation with
      degenerative neuropathy.

PMID- 15169651
TI  - [Cloning and prokaryotic expression of heat shock protein 70 gene of
      Mycobacterium tuberculosis].
AB  - AIM: To clone the heat shock protein 70 (Hsp70) gene of Mycobacterium
      tuberculosis and express it in E.coli. METHODS: Hsp70 gene was amplified by PCR
      from Mycobacterium tuberculosis H37Rv, then inserted into pUC19 vector and
      sequenced. The recombinant expression plasmid pGEX-TBhsp70 was constructed and
      expressed in E.coli. RESULTS: Hsp70 gene was obtained form Mycobacterium
      tuberculosis and its sequence was identical with that reported in GenBank. The
      E.coli. containing pGEX-TBhsp70 could express a protein with M(r) being 96,000
      after induction of IPTG. CONCLUSION: A confirmed Hsp70 gene is cloned and
      expressed in E.coli successfully, which lay the foundation for the related
      research of the gene.

PMID- 15169652
TI  - [Induction of specific humoral immune response in mice by recombinant mutant HBV
      s gene vaccine].
AB  - AIM: To construct the recombinant eukaryotic expression vector pCMV-S2. S +
      145R(PR) containing mutant HBV s gene and detect the specific humoral immune
      response to the PR in mice. METHODS: The PR was constructed by positional cloning
      of restriction endonuclease, and then it was transfected into human
      hepatocellular carcinoma cell line Hep G2 through electrotransformation. The
      antigenicity of PR was examined by EIA, ELISA and immunocytochemical staining.
      The PR and empty vector pcDNA3.0 were then used respectively to immunize
      intramuscularly 5 C57BL/6 mice, dosage being 100 pg purified plasmid each mouse.
      The titers of serum anti-HBs and anti-HBs2 antibodies were detected by ELISA.
      RESULTS: In vitro experiment showed that mutant HBsAg could bind to anti-HBs
      antibody. The PR could induce anti-HBs and anti-HBs2 antibody production in
      immunized mice. But the appearance time of serum anti-HBs2 antibody one or two
      weeks earlier than that of serum anti-HBs antibody. CONCLUSION: The expression
      product of PR had a good antigenicity, which can induce specific hu-moral immune
      response in C57BL/6 mice.

PMID- 15169654
TI  - [Expressions of c-fos in different brain regions after microinjection of 5-HT3
      receptors agonist in hippocampus].
AB  - AIM: To explore the neuronal circuit and possible pathway related to the 5-HT3
      receptors in hippocampus neuroimmunomodulation. METHODS: SABC immunocytochemical
      staining was used to detect the c-fos expression. RESULTS: A large number of FOS
      positive neurons expression were found in the hippocampus and brain cortex at 1
      hour after microinjection of 5-HT3 receptor agonist (I-PBG) in the hippocampus,
      but as time went on, the number of FOS positive-neurons gradually decrease. A
      small number of FOS positive-neurons were found only in the hypothalamus and gray
      matter around acqueduct of midbrain, respectively at 8 and 16 hs after injection
      of 1-PBG. The expression of c-fos induced by 1-PBG could be blocked by pre
      microinjection of tropisetron. CONCLUSION: Brain cortex-hippocampus hypothalamus
      gray matter around acqueduct of midbrain forma neuronal network, which may be
      related to immunomodulation.

PMID- 15169653
TI  - [The relationship between abnormal apoptosis and Fas expression of thymocytes
      from patients with myasthenia gravis].
AB  - AIM: To explore the roles of abnormalities of thymocytic abnormal apoptosis and
      its Fas expression in patients with myasthenia gravis (MG) in generation of
      autoimmune response. METHODS: The thymocytes were isolated and thymus extractive
      was prepared from fresh thymic tissue excised from MG patients. The proliferation
      of thymocyes was evaluated by MTT colorimetry. The apoptosis of thymocytes were
      examined by DNA electrophoresis. Expression of Fas was analyzed by a FACScan flow
      cytometry. Transcription and mutation of Fas gene were detected by RT-PCR and
      single-stranded conformation polymorphism ( SSCP) analysis. RESULTS: Thymus
      extractive could inhibit proliferation of normal thymocytes, while had no
      influence on the thymocytic proliferation of MG patients. The proliferation of
      thymocytes of both normal persons and MG patients could be inhibited by thymus
      extractive in the presence of dexamethasone. The inhibition rates were 58. 33%
      and 54. 26% respectively. The cocultured thymocytes with dexamethasone showed
      characteristic apoptosis pattern and the DNA electrophoresis exhibited 'ladder'
      appearance. The abnormal bands in Fas mRNA of partial MG patients' thymocytes
      were found by RT-PCR-SSCP analysis. CONCLUSION: Abnormalities of apoptosis and
      Fas gene expression of MG patients' thymocytes, and Fas gene mutation may be
      related to the pathogenesis and progression of MG.

PMID- 15169655
TI  - [Study on detecting the sensitivity of tumor cells to chemotherapeutic agents by
      immunohistochemical staining with anti-ssDNA mAb].
AB  - AIM: To explore the possibility of application of self-made anti-ssDNA mAb to
      detecting the apoptosis of tumor cells induced by chemotherapeutic drugs and
      evaluate the sensitivity of tumor cells to chemotherapeutic drugs from a
      apoptotic rate. METHODS: Apoptosis of both K562 and Hep-2 cells were induced by
      maximum plasma concentrations of 9 different chemotherapeutic drugs. The
      apoptosis of tumor cells was detected by immunohistochemical ( IHC) staining with
      anti-ssDNA mAb and their apoptotic rate were calculated. RESULTS: The apoptotic
      cells could be differentiated from non-apoptotic cells by the HIC staining with
      anti-ssDNAmAb. The apoptosis of tumor cells were induced by chemotherapeutic
      drugs, but apoptotic extent of different tumor cells, even the same one tumor
      cell, was distinct when they exposed to all kinds of anti-tumor drugs.
      CONCLUSION: The combination of anti-ssDNA mAb with IHC staining can be used to
      detect the sensitivity of tumor cells to chemotherapeutic drugs.

PMID- 15169656
TI  - [The expression of acetyl-heparanase, laminin and laminin receptor and their role
      in the metastasis of ovarian cancer].
AB  - AIM: To explore the expressions of acetyl-heparanase mRNA, laminin ( LN) and
      laminin receptor ( LR) in 50 ovarian carcinoma, 33 ovarian carcinoma with lymph
      node metastasis, and 10 serous ovarian cystadenoma as well as their role in the
      metastasis of ovarian cancer. METHODS: The transcription level of acetyl
      heparanase mRNA, expressions of LN and LR were detected by in situ hibridization
      and immunohistochemical staining, respectively. RESULTS: The transcription level
      of acetyl-heparanase mRNA in ovarian carcinoma tissue and metastatic lymph nodes
      increased significantly, but its expression in primary focus was notably higher
      than that in metastatic lymph nodes (P < 0. 05 ). There was low expression of
      acetyl-heparanase mRNA in serous ovarian cystadenoma. The expression of acetyl
      heparanase mRNA in malignant and benign tumor tissues had markedly difference (P
      < 0. 01 ). Expressions LN in both tissues mentioned above decreased while LR
      expression was high. The expression of acetyl-heparanase mRNA was negative
      correlation with that of LN, while positive with that of LR. CONCLUSION: The
      correlation among expressions of acetyl-heparanase mRNA, LN and LR suggests that
      heparanase is involved in the growth, invasion and metastasis of ovarian
      carcinoma.

PMID- 15169657
TI  - [VEGF production and its receptor expression of MPhis in peritoneal fluid].
AB  - AIM: To explore the role of microenvironment of peritoneal fluid in pathogenesis
      of endometriosis, the source and its regulation in peritoneal fluid. METHODS:
      Peritoneal Mphis from 14 patients with endometriosis (endometriosis group)and 10
      normal women ( control group) were cultured in vitro. Either 17-l estradiol,
      progesterone and LPS or their combinant were added to cultured peritoneal Mos
      from control group. VEGF levels in culture supernatant of M(Ds from two groups
      were detected by ELISA. Culture supernatant of serum-free media in two groups
      were added to the cultured endothelial cells. Effect of the supernatant on
      endothelial cell proliferation activity was examined by MTT colorimetry at
      wavelength of 450 nm. The expressions of Fit-1 and Flt-4 on the Mos from two
      groups were determined by immunohistochemical staining. RESULTS: The VEGF level
      in culture supernatant of Mps from endometriosis group was significantly higher
      than that from control group (P < 0. 05 ), and had no cyclic variation (P > 0.
      05). As compared with LPS, estrogen and progentrogen could elevate notably the
      level ofVEGF secreted by Ms ( P < 0. 05 ). However, the regulation of MWs
      secreted VEGF level by estrogen and progestoron had no marked difference. The Mos
      activated by LPS could strengthen the regulation of VEGF secreted by Mphis under
      estrogen and progestron stimulation. Culture supernatant of serum-free media for
      Mos could promote significantly the proliferation of endothelial cells ( P < 0.
      05 ). Fit-land Flt-4 on Mos was expressed without cyclic variation (P>0.05).
      CONCLUSION: The VEGF may be secreted by Mos in peritoneal fluid of endometriosis
      group. The endothelial cell proliferation and angiogenesis are enhanced by change
      of microenvironment of peritoneal fluid.

PMID- 15169658
TI  - [Relationship between expression of BLCAP protein and malignancy of
      osteosarcoma].
AB  - AIM: To study the relationship between expression of bladder cancer-associated
      protein (BLCAP) and malignancy of osteosarcoma. METHODS: SABC method was applied
      to study the expression of BLCAP protein in osteosarcoma, according to clinical
      results, to analyze the prognosis value of BLCAP protein in osteosarcoma.
      RESULTS: The positive rate of BLCAP protein in primary osteosarcoma was
      65.6%,much higher than that in recurrent osteosarcoma, which was 25.0%.
      CONCLUSION: It may be helpful for evaluating the prognosis of osteosarcoma to
      study the relationship between expression of BLCAP protein and malignancy of
      osteosarcoma.

PMID- 15169659
TI  - [Clinical significance of inflammatory reaction in patients with coronary heart
      disease].
AB  - AIM: To explore the relationship between inflammatory reaction and coronary heart
      disease (CHD). METHODS: 101 CHD patients were divided into 3 groups, namely 19 ca
      ses of stable angina pectoris ( SAP) , 33 cases of unstable angina pectoris( UAP)
      and 49 cases of acute myocardial infarction( AMI). Control group C-reactive
      protein( CRP) level and sum of white blood cells ( WBC) in peripheral blood were
      detected by immunoturbidimetry and hemocytometer,respectively. Pathological
      changes in 20 AMI tissue slice were examined by histochemical staining. RESULTS:
      The CRP level and sum of WBCs in UAP group were higher than those in SAP group (
      P < 0. 05 ), but distinctly lower than those in AMI group (P<0.01). The CRP level
      and sum of WBCs in AMI group and UAP group were notably higher than those in
      normal control group (P <0. 01). Histochemical staining showed that there were a
      great number of leucocyte in-filtration in cardiac muscle of AMI patients.
      CONCLUSION: The inflammatory reaction participants in genesis and development of
      CHD. CRP level and sum of WBCs may become a useful index for monitoring CHD
      patient's condition and prejudging the risk of suffering from CHD.

PMID- 15169660
TI  - [In-vivo screening and characterization of peptides specific for vasculature of
      gastric cancer].
AB  - AIM: To screen in vivo from a phage-displayed peptide library polypeptide
      fragments specific binding to vascular endothelial cells of gastric cancer
      xenografts, so as to provide for anti-angiogenesis therapy of tumor. METHODS:
      Immunosupressed mice models for human gastric cancer xeno-grafts were established
      by subrenal capsular assay (SR-CA). The 12-peptide library was panned through 4
      rounds. Phages were recovered and titrated from tumor xenografts and control
      tissue (brain). The distribution of phage were detected in transplanted tumor
      tissues by immunohistochemical staining. RESULTS: Phage homing to gastric cancer
      xenografts were enriched through four rounds of panning,being 3.4-fold of that
      recovered from brain tissue. Peptide sequences were characterized for randomly
      picked-upclones and the peptide sequence YESIRIGVAPSQ appeared most frequently.
      Immunohistochemical staining for the homing phage revealed a specific vascular
      endothelial cell localization in gastric cancer xenografts 5 min after injection
      of the enriched phages. When the specific phage individually test-ed, the phage
      recovered from gastric cancer xenografts were as 4. 2 times as those from control
      tissue ( brain) , as 4.9 times as those from lung, as 5.4 times as those from
      heart. CONCLUSION: The tumor-specific homing peptides may provide a effective
      tool for targeting tumor vasculature in anti-angiogenesis therapy of cancer. The
      in vivo selection technique in this study was feasible and applicable to
      screening peptides homing to vascular endothelial cells.

PMID- 15169661
TI  - [Construction and screening of hepatitis E virus-specific phage antibody
      combinatorial library].
AB  - AIM: To construct HEV-specific phage combinatorial anti-body library and screen
      anti-HEV antibodies with neutralizing activity from the library. METHODS: The
      total RNA was extracted from B-lymphocytes of 6 HE patients. Kappa chain and Fd
      segment of IgG gene were amplified respectively by RT-PCR using a set of Fab
      specific primers. The amplified gene were inserted successively into vector
      pComb3 and electrotransformed E. coli XLI-Blue cells. Furthermore, the
      recombinant phage was rescued by being concultured with helper phage VCSM13 to
      construct HEV-specific phage anti-body library. RESULTS: Fab displayed on the
      surface a as fusion protein with the N terminal of coat protein III, and 1. 8 x
      10(7) clone library was established. Specific antibodies to HEV ORF2 recombinant
      antigen were acquired after five rounds of panning with HEV ORF2 recombinant
      antigen including neutralizing epitope. CONCLUSION: Four clones exhibited
      specific binding to HEV ORF2 recombinant antigen including neutralizing epitope
      is identified by ELISA. The results show that we have got the recombinant phage
      antibodies.

PMID- 15169662
TI  - [Construction and characterization of anti-DOTA-Y phage antibody library].
AB  - AIM: To construct a anti-dodecane-tertraacetic acid-yttrium(DOTA-Y) immune Fab
      phage antibody library. METHODS: BALB/c were immunized with BSA-Y-DOTA which was
      prepared by DOTA-conjugated BSA and chelated with Y. After determination of anti
      serum, total RNA was extracted from splenic lymphocytes of immuned mice. The
      heavy chain Fd and light chain Kappa genes repertoires of immunoglobulin were
      amplified respectively by RT-PCR, and then the amplified products were cloned
      into the reconstructive phage vector pComb3M to construct anti-DOTA-Y Fab
      antibody. And then, the recombination rate, diversity and display of Fab antibody
      library were identified by restriction endonuclease digestion, DNA sequencing and
      ELISA. RESULTS: BSA-Y-DOTA was prepared successfully, and a higher titer of
      immune sera was achieved. The amplified gene fragments of Fd and Kappa chain by
      RT-PCR were correct and the length was with about 650 bp, and were inserted
      exactly. The sink size of Fab phage display library reached 8 x 10(7), the re
      combination rate was about 90%, and it possesed great diversity. In addition,
      ELISA detection showed that there was Fab expression on the phage library.
      CONCLUSION: An immune Fab phage antibody library of DOTA-Y has been constructed
      successfully, which lays a solid foundation for screening specific anti-DOTA-Y
      antibody.

PMID- 15169663
TI  - [Construction and expression of prokaryotic expression vector of GAP-43 and
      preparation of monoclonal antibody against GAP-43].
AB  - AIM: To express the growth-associated protein-43 (GAP-43)in prokaryotic cells and
      prepare monoclonal antibody( mAb)against GAP-43. METHODS: Full length sequence of
      GAP-43 gene was amplified from the plasmid containing pGAP-43cDNA and was cloned
      into the expression vector pGEX-4T-I.GST-GAP-43 fusion protein was expressed in
      E. coil under IPTG induction. Expressed fusion protein was purified by glutathine
      agarose chromagraphy, Using purified protein as an immunogen, mAb against GAP-43
      was prepared. RESULTS: The recombinant plasmid containing the target gene was
      constructed successfully. The fusion protein was expressed in E. coli in soluble
      form. The titer of anti-GAP-43mAb in ascites was 1: 10'. The Ig subclass and
      subtype of the mAb was IgG2a and K type, respectively. Specificity of the mAb was
      confirmed by ELISA, Western blot and immunofluorescence technique. CONCLUSION:
      The anti-GAP-43 mAb obtained has strong specificity and high titer, which
      provides an useful reagent for further studying the function of GAP-43 in nervous
      system.

PMID- 15169664
TI  - [Prokaryotic expression and bioactivity identification of Fab against human gamma
      seminoprotein].
AB  - AIM: To construct the expression vector containing cDNA encoding Fab against
      human gamma-seminoprotein and express it in E. coli. METHODS: The genes encoding
      K chain and Fd against gamma-seminoprotein were acquired from pUC19-K and
      pBluescript KS( M13-)-Fd by restrictive enzyme digestion and then cloned into the
      expression vector pComb3 to construct recombinant expression vector pComb3-Fab.
      pComb3-Fab was transfected into and expressed in XLI-Blue. RESULTS: Fab against r
      semino-protein was expressed in. XLI-Blue. Western blot analysis and
      immunocytochemical staining demonstrated that ex-pressed Fab could specifically
      bind to gamma-seminoprotein. CONCLUSION: Fab against gamma -seminoprotein has
      been expressed successfully with biological activity, which create favourable
      condition for further study on targeted therapy of prostate cancer.

PMID- 15169665
TI  - [Preparation of rabbit anti-Syk antibody and its application in breast cancer
      diagnosis].
AB  - AIM: To prepare rabbit anti-Syk antibody and analysis its application in breast
      cancer diagnosis. METHODS: The rabbits were immunized with recombinant mouse Syk
      protein to prepare antibody against Syk. The purity and specificity of the
      antibody were analyzed by Western blot. The expression of Syk protein was
      detected by immunohistochemical staining. RESULTS: The titer of serum anti-Syk
      antibody was 1:6 400 (A450 = 1. 03) 6 weeks after the immunization. The SDS-PAGE
      and Western blot analysis showed that there was a obvious protein band with Mr
      72,000, confirming the specificity of obtained anti-Syk antibody. It was
      displayed by immunohistochemical staining with anti-Sykantibody that in normal
      breast tissue Syk was high expression; while in infilfrative dustal carcinoma of
      breast tissue the expression of syk was negative. CONCLUSION: The rabbit anti-Syk
      antibody with high titer and specificity has been prepared. The Syk is high
      expression in normal breast tissue, but is deficient in breast cancer tissue. The
      result may be useful for clinical diagnosis of breast cancer.

PMID- 15169666
TI  - [Effect of glia cell line-derived neurotrophic factor on cultured spinal motor
      neurons from embryonic rat].
AB  - AIM: To observe the effects of various concentrations of gli-a cell line-derived
      neurotrophic factor ( GDNF) on the growth of cultured spinal motor neurons from
      embryonic rat. METHODS: Neurons were isolated from embryonic rat spi-nal ventral
      tissue and then were primarily cultured in vitro. Morphological feature of
      neurons was examined by immuno-cytochemical staining with mAb SMI-32. The effect
      of GDNFon growth of spinal motor neurons was detected by MTT colorimetry.
      RESULTS: GDNF could significantly enhance the survival and neurite outgrowth of
      rat spinal motor neurons cultured in vitro in dose-dependent tendency.
      CONCLUSION: Varying concentrations of GDNF can enhance the growth of embryonic
      rat spinal motor neurons to various extent.

PMID- 15169667
TI  - [Experimental study on the in vitro resistance to Toxoplasma gondii by murine
      lymphocyte].
AB  - AIM: To study the activities of in vitro resistance to the tachyzoite of
      Toxoplasma gondii by murine lymphocytes. METHODS: The rat's splenocyte culture
      method was used to observe the effects of lymphocytes themselves and lymphocytes
      together with Mandelic( MA) on the invasion and proliferation of T. gondii in
      lymphocytes. At the same time acetylspiramycin was used as positive control.
      RESULTS: As compared with other somatic cells, the lymphocytes invaded by T.
      gondii still inhibited and killed the toxoplasma organisms in the presence of
      immunity, the effect safety dose of MA on inhibition of the invasion of T. gondii
      was not notable while the inhibition of the proliferation of T. gondii in
      lymphocytes was remarkable. CONCLUSION: Cell-mediated immunity(CMI) was an
      important factor that host resists the T. gondii infection. So, we should pay
      attention to improving the organism's CMI and take proper medicine so as to
      enhance the effect of lymphocyte's resistance to T. gondii.

PMID- 15169668
TI  - [Effect of insulin on apoptosis of cultured human trophoblast cells and its
      mechanism].
AB  - AIM: To explore the effect of insulin on apoptosis of cultured human trophoblast
      cells and its possible mechanism. METHODS: Human trophoblast cells from early
      pregnancy women were cultured and divided into 3 groups; normal control group;
      H2O2, treatment group and insulin plus H2O2 treatment group. H2O2 was used to
      induce apoptosis of trophoblasts cells. Apoptotic rate was detected by flow
      cytometry. The effects of insulin on Bcl-2 expression and caspase-3 activity were
      also detected. RESULTS: H2O2 might induce apoptosis of trophoblast cells and
      typical morphological features of apoptotic cells was observed under electron
      microscope. Flow cytometry detection exhibited that insulin could reduce markedly
      H2O2-induced apoptotic rate of trophoblasts cells (P < 0. 01). Bcl-2 expression
      rate inH,O, treatment group was significantly lower than that in control group (P
      < 0. 01), while caspase-3 activity was distinctly higher than that in control
      group (P < 0. 01). CONCLUSION: Insulin could inhibit apoptosis of human
      trophoblasts cells induced by H2O2, which be may through decreased caspase-3
      activity and increased Bcl-2 protein expression.

PMID- 15169669
TI  - [Eukaryotic expression of human LIGHT-Fc chimeric molecule and its anti-tumor
      activity].
AB  - AIM: Construct eukaryotic expression plasmid of hLIGHT-Fc gene and express hLIGHT
      Fc fusion protein with high biological activity. METHODS: Utilizing PCR to clone
      the human LIGHT cDNA from a normal human activated T cells cDNA library phAD.
      CAD, then using SOE (splicing by overlap extension) technique to fuse CD137
      signal peptide gene into LIGHT extramembrane domain encoding sequence, inserting
      this recombinated LIGHT cDNA with human IgGI Fc cDNA into the eukaryotic
      expression plasmid pcDNA3, expressed it transiently in 293T cells, and purified
      by recombinated protein A affinity chromatography column, at last we checked its
      Mr, purity and anti-tumor activity. RESULTS: LIGHT-Fc gene's ORF is right and
      coincident with we expected, then its expression was confirmed by ELISA and SDS
      PAGE, and we proved that the purified LIGHT-Fc protein could inhibit the growth
      of some cultured tumor cell lines by MTT. CONCLUSION: we got a purified
      recombinated protein of LIGHT-Fc with anti-tumor activity and the anticipated Mr,
      thus lay a foundation for further works on LIGHT such as its role in immune
      homeostasis,the mechanism of its receptors' signal transduction, et al.

PMID- 15169670
TI  - [Effect of adenosine and anti-IgE antibody on histamine release from mast cells
      in BALF of asthma patients].
AB  - AIM: To investigate the functional properties of mast cells in bronchoalveolar
      lavage fluid (BALF) of asthma patients. METHODS: 29 asthma patients in the
      recovery phase were enrolled in the study and their bronchoalveolar lavages (BAL)
      were inspected under fibreoptics bronchoscope. The cells from each BAL
      fluid(BALF) were added to LP4 tubes containing anti-IgE antibody, adenosine,
      buffer or anti-IgE antibody + adenosine, and incubated at 37 degrees C for 20
      min. The reactions were stopped by placing the tubes on ice and adding 100 microL
      of cold incomplete Hank's balanced salt solution (HBSS). The histamine
      chromogenic assay was performed to detect histamine released from mast cells in
      BALF. Histamine release was expressed in a net release percentage. RESULTS: 100
      micromol/L of adenosine failed to induce histamine release from mast cells; while
      1,000 micromol/L of adenosine could induce about 17% histamine release from mast
      cells in BALF; For anti-IgE antibody, as low as 1 x 10(-4) g/L of anti-IgE was
      able to induce approximately 20% histamine release from the mast cells. When the
      anti-IgE antibody was combined with adenosine, only 3 x 10(-5) g/L of anti-IgE
      antibody + adenosine could exert synergistic effectiveness. CONCLUSION: Mast
      cells in BALF from asthma patients had a poor reaction to adenosine
      stimulation,but are much more sensitive to anti-IgE antibody-dependent
      stimulation; only as low as 3 x 10(-5) g/L of anti-IgE antibody is able to
      cooperate with adenosine.

PMID- 15169671
TI  - [Effect of antisense CD40 RNA on CD40 expression and proliferation of EB virus
      transformed B lymphocytes].
AB  - AIM: To investigate the changes of CD40 expression and proliferation pattern of
      EB virus-transformed B lymphocytes that had been transfected by antisense CD40
      RNA. METHODS: Eukaryotic expression vector pcDNA3/CD40 of human CD40antisense RNA
      was constructed by means of T-A cloning and subcloning, and then was transfected
      into EB virus-transformed B lymphocytes. Changes of CD40 expression on the B
      cells and their proliferation were tested by flow cytometry and MTT colorimetry
      assay, respectively. RESULTS: CD40 expression and proliferation of the B cells
      transfected with antisense CD40 RNA were significantly lower than those of the
      cells transfected with pcDNA3 alone (P < 0. 01). CONCLUSION: Antisense CD40 RNA
      may be served as an effective means of regulating immune function, and the CD40
      gene itself also play an important role in cell proliferation.

PMID- 15169672
TI  - [The influence of the extract of lumbricus on the production of NO and TNF-alpha
      by mouse MPhi and splenocytes].
AB  - AIM: To explore the effect of the abstracts of lumbricus on the secretion of NO
      and TNF-alpha by mouse Mphi s and splenocytes. METHODS: Murine Mphi s and spleen
      cell were co-cultured with various doses of lumbricus abstracts for 24 hours and
      then the supernate was collected. The levels of NO and TNF-alpha were detected by
      diazotization reaction and MTT colorimetry, respectively. RESULTS: Compared with
      control group, 0.1 g/L of lumbricus abstracts could increase the NO level and
      antagonize the inhibition of dexamethasone(Dex). 1 x 10(-4), 1 x 10(-3) g/L of
      lumbricus abstracts could increase TNF-alpha level and also antagonize the
      inhibition of Dex on the secretion of TNF-alpha by Mphi s and splenic cells.
      CONCLUSION: The abstracts of lumbricus can activate Mphi s and splenic cells to
      secrete NO and TNF-alpha and antagonize the inhibition effect of Dex on these
      cells.

PMID- 15169673
TI  - Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8
      gene expression in lung epithelial cells.
AB  - Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an
      activator for neutrophils, T cells, and other immune cells. The airway and
      respiratory epithelia play important roles in the initiation and modulation of
      inflammatory responses via production of cytokines and surfactant. The
      association between elevated levels of nitric oxide (NO) and IL-8 in acute lung
      injury associated with sepsis, acute respiratory distress syndrome, respiratory
      syncytial virus infection in infants, and other inflammatory diseases suggested
      that NO may play important roles in the control of IL-8 gene expression in the
      lung. We investigated the role of NO in the control of IL-8 gene expression in
      H441 lung epithelial cells. We found that a variety of NO donors significantly
      induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an
      increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8
      gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not
      inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors
      of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP
      did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA
      levels independently of changes in the intracellular cGMP levels. NO induction of
      IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated
      kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl
      radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating
      the involvement of hydroxyl radicals in the induction process. NO induction of IL
      8 gene expression could be a significant contributing factor in the initiation
      and induction of inflammatory response in the respiratory epithelium.

PMID- 15169674
TI  - Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'
      untranslated regions in the developing human lung.
AB  - In preparation for birth, lung epithelia must switch from net fluid secretion,
      required for lung development, to net absorption, which prepares the lungs for
      postnatal gas exchange. The apical membrane amiloride-sensitive epithelial Na
      channel (ENaC) is the rate-limiting step for Na+ and fluid absorption. Expression
      of alpha-ENaC mRNA has been detected in human lung as early as the embryonic
      stage of development. However, humans express multiple transcripts for alpha
      ENaC, containing differing 5'-untranslated regions (UTR) with unknown effects on
      protein translation, and different ontogenies for individual transcripts could
      provide a novel mechanism for developmental regulation of ENaC function. To
      assess the relative expression of the two most abundant alpha-ENaC transcripts
      (alpha-ENaC1 and alpha-ENaC2) during lung development, we performed
      nonradioactive in situ hybridization using probes specific to the alternative 5'
      UTRs. Both transcripts were expressed throughout intrauterine lung development (8
      to 40 wk gestation), and expression was localized to the surface epithelial cells
      of the conductive and respiratory airways in both ciliated cells and nonciliated
      Clara cells. alpha-ENaC mRNA expression was also identified in the serous cells
      of the submucosal glands surrounding the proximal airways. In the mature prenatal
      lung, subsets of alveolar type II (ATII) cells expressed one or both of the alpha
      ENaC transcripts. Our observations demonstrate that a developmentally regulated
      switch between alpha-ENaC 5'-UTR variants is not the trigger by which the
      developing human lung becomes a fluid-absorbing organ at birth, that individual
      ATII cells express neither, one, or both of the alpha-ENaC transcripts, and that
      the overall expression is linked to epithelial cell differentiation and lung
      maturation.

PMID- 15169675
TI  - Modulation of airway inflammation and bacterial clearance by epithelial cell ICAM
      1.
AB  - Many cell types in the airway express the adhesive glycoprotein for leukocytes
      intercellular adhesion molecule-1 (ICAM-1) constitutively and/or in response to
      inflammatory stimuli. In this study, we identified functions of ICAM-1 on airway
      epithelial cells in defense against infection with Haemophilus influenzae.
      Initial experiments using a mouse model of airway infection in which the
      bacterial inoculum was mixed with agar beads that localize inflammation in
      airways demonstrated that ICAM-1 expression was required for efficient clearance
      of H. influenzae. Airway epithelial cell ICAM-1 expression required few or no
      leukocytes, suggesting that epithelial cells could be activated directly by
      interaction with bacteria. Specific inhibition of ICAM-1 function on epithelial
      cells by orotracheal injection of blocking antibodies resulted in decreased
      leukocyte recruitment and H. influenzae clearance in the airway. Inhibition of
      endothelial cell ICAM-1 resulted in a similar decrease in leukocyte recruitment
      but did not affect bacterial clearance, indicating that epithelial cell ICAM-1
      had an additional contribution to airway defense independent of effects on
      leukocyte migration. To assess this possibility, we used an in vitro model of
      neutrophil phagocytosis of bacteria and observed significantly greater engulfment
      of bacteria by neutrophils adherent to epithelial cells expressing ICAM-1
      compared with nonadherent neutrophils. Furthermore, bacterial phagocytosis and
      killing by neutrophils after interaction with epithelial cells were decreased
      when a blocking antibody inhibited ICAM-1 function. The results indicate that
      epithelial cell ICAM-1 participates in neutrophil recruitment into the airway,
      but its most important role in clearance of H. influenzae may be assistance with
      neutrophil-dependent bacterial killing.

PMID- 15169676
TI  - Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar
      epithelial cell monolayers.
AB  - We characterized immunoglobulin G (IgG) transport across rat alveolar epithelial
      cell monolayers cultured on permeable supports. Unidirectional fluxes of biotin
      labeled rat IgG (biot-rIgG) were measured in the apical-to-basolateral (ab) and
      opposite (ba) directions as functions of [rIgG] in upstream fluids at 37 and 4
      degrees C. We explored specificity of IgG transport by measuring fluxes in the
      presence of excess Fc, Fab, F(ab')2, or chicken Ig (IgY). Expression of the IgG
      receptor FcRn and the effects of dexamethasone on FcRn expression and biot-rIgG
      fluxes were determined. Results show that ab flux of biot-rIgG is about fivefold
      greater than ba flux at an upstream concentration of 25 nM biot-rIgG at 37
      degrees C. Both ab and ba fluxes of rIgG saturate, resulting in net absorption
      with half-maximal concentration and maximal flow of 7.1 nM and 1.3 fmol.cm(-2).h(
      1). At 4 degrees C, both ab and ba fluxes significantly decrease, nearly
      collapsing net absorption. The presence of excess unlabeled Fc [but not Fab,
      F(ab')2, or IgY] significantly reduces biot-rIgG fluxes. RT-PCR demonstrates
      expression of alpha- and beta-subunits of rat FcRn. Northern analysis further
      confirms the presence of alpha-subunit of rat FcRn mRNA of approximately 1.6 kb.
      Dexamethasone exposure for 72 h decreases the steady-state level of mRNA for rat
      FcRn alpha-subunit and the ab (but not ba) flux of biot-rIgG. These data indicate
      that IgG transport across alveolar epithelium takes place via regulable FcRn
      mediated transcytosis, which may play an important role in alveolar homeostasis
      in health and disease.

PMID- 15169677
TI  - A "virtual gland" method for quantifying epithelial fluid secretion.
AB  - We developed a new apparatus, the virtual gland (VG), for measuring the rate of
      fluid secretion (Jv), its composition, and the transepithelial potential (TEP) in
      cultured epithelial cells under open circuit. The VG creates a 10-microl chamber
      above the apical surface of epithelial cells on a Costar filter with a small hole
      leading to an oil-filled reservoir. After the chamber is primed with a fluid of
      choice, secreted fluid is forced through the hole into the oil, where it forms a
      bubble that is monitored optically to determine Jv and collected for analysis.
      Calu-3 cells were mounted in the VG with a basolateral bath consisting of Krebs
      Ringer bicarbonate buffer at 37 degrees C. Basal Jv was 2.7 +/- 0.1 microl x cm(
      2) x h(-1) (n = 42), and TEP was -9.2 +/- 0.6 mV (n = 33); both measures were
      reduced to zero by ouabain (n = 6) x Jv and TEP were stimulated 64 and 59%,
      respectively, by 5 microM forskolin (n = 10), 173 and 101% by 1 mM 1-ethyl-2
      benzimidazolinone (n = 5), 213 and 122% by 333 nM thapsigargin (n = 5), and 520
      and 240% by forskolin + thapsigargin (n = 6). Basal Jv and TEP were inhibited to
      82 and 63%, respectively, with 10 microM bumetanide (n = 5), 71 and 82% with 100
      microM acetazolamide (n = 5), and 47 and 56% with 600 microM glibenclamide (n =
      4). Basal Jv and TEP were 52 and 89% of control values, respectively, after HCO3-
      replacement with HEPES (n = 16). The net HCO3- concentration of the secreted
      fluid was close to that of the bath (25 mM), except when stimulated with
      forskolin or VIP, when it increased (approximately 80 mM). These results validate
      the use of the VG apparatus and provide the first direct measures of Jv in Calu-3
      cells.

PMID- 15169678
TI  - Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II
      cells.
AB  - Pulmonary surfactant is a lipoprotein complex that functions to reduce surface
      tension at the air liquid interface in the alveolus of the mature lung. In late
      gestation glycogen-laden type II cells shift their metabolic program toward the
      synthesis of surfactant, of which phosphatidylcholine (PC) is by far the most
      abundant lipid. To investigate the cellular site of surfactant PC synthesis in
      these cells we determined the subcellular localization of two key enzymes for PC
      biosynthesis, fatty acid synthase (FAS) and CTP:phosphocholine
      cytidylyltransferase-alpha (CCT-alpha), and compared their localization with that
      of surfactant storage organelles, the lamellar bodies (LBs), and surfactant
      proteins (SPs) in fetal mouse lung. Ultrastructural analysis showed that immature
      and mature LBs were present within the glycogen pools of fetal type II cells.
      Multivesicular bodies were noted only in the cytoplasm. Immunogold electron
      microscopy (EM) revealed that the glycogen pools were the prominent cellular
      sites for FAS and CCT-alpha. Energy-filtering EM demonstrated that CCT-alpha
      bound to phosphorus-rich (phospholipid) structures in the glycogen. SP-B and SP
      C, but not SP-A, localized predominantly to the glycogen stores. Collectively,
      these data suggest that the glycogen stores in fetal type II cells are a cellular
      site for surfactant PC synthesis and LB formation/maturation consistent with the
      idea that the glycogen is a unique substrate for surfactant lipids.

PMID- 15169679
TI  - Demonstrating drug action.

PMID- 15169680
TI  - Clinical utility as a criterion for revising psychiatric diagnoses.
AB  - OBJECTIVE: Changes in DSM-IV were guided by empirical data that mostly focused on
      improving diagnostic validity and reliability. Although many changes were made
      explicitly to improve clinical utility, no formal effort was made to empirically
      determine actual improvements in clinical utility. The authors propose that
      future revisions of DSM empirically demonstrate improvement in clinical utility
      to clarify whether the advantages of changing the diagnostic criteria outweigh
      potential negative consequences. METHOD: The authors provide a formal definition
      of clinical utility and then suggest that the merits of a proposed change to DSM
      be evaluated by considering 1) its impact on the use of the diagnostic system, 2)
      whether it enhances clinical decision making, and 3) whether it improves clinical
      outcome. RESULTS: Evaluating a change based on its impact on use considers both
      user acceptability and accuracy in application of the diagnostic criteria. User
      acceptability can be measured by surveying users' reactions, assessing user
      acceptability in a field trial setting, and measuring the effects on ease of use.
      Assessment of the correct application of diagnostic criteria entails comparing
      the clinician's diagnostic assessment to expert diagnostic assessment.
      Assessments of the impact on clinical decision making use methods developed for
      evaluating adherence to practice guidelines. Improvement in outcome entails
      measuring reduction in symptom severity or improvement in functioning or in
      documenting the prevention of a future negative outcome. CONCLUSIONS: Empirical
      methods should be applied to the assessment of changes that purport to improve
      clinical utility in future revisions of DSM.

PMID- 15169681
TI  - Bridging community intervention and mental health services research.
AB  - OBJECTIVE: This article explores the potential of community intervention
      perspectives for increasing the relevance, reach, and public health impact of
      mental health services research. METHOD: The authors reviewed community
      intervention strategies, including public health and community development and
      empowerment interventions, and contrast community intervention with practice
      based quality improvement and policy research. RESULTS: A model was proposed to
      integrate health services and community intervention research, building on the
      evidence-based strength of quality improvement and participatory methods of
      community intervention to produce complementary functions, such as linking
      community-based case finding and referral with practice-based quality
      improvement, enhanced by community-based social support for treatment adherence.
      CONCLUSIONS: The community intervention approach is a major paradigm for
      affecting public health or addressing health disparities. Despite challenges in
      implementation and evaluation, it represents a promising approach for extending
      the reach of mental health services interventions into diverse communities.

PMID- 15169683
TI  - Transference love: an artificial rose?

PMID- 15169685
TI  - Placebo-controlled evaluation of four novel compounds for the treatment of
      schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: Four studies using identical protocols evaluated the safety and
      efficacy of four novel, evidence-based targets for antipsychotic agents: a
      neurokinin (NK(3)) antagonist (SR142801), a serotonin 2A/2C (5-HT(2A/2C))
      antagonist (SR46349B), a central cannabinoid (CB(1)) antagonist (SR141716), and a
      neurotensin (NTS(1)) antagonist (SR48692). METHOD: Adults with schizophrenia or
      schizoaffective disorder (N=481) were randomly assigned in a 3:1:1 ratio to
      receive fixed doses of investigational drug, placebo, or haloperidol for 6 weeks.
      Primary efficacy variables included changes from baseline in total score on the
      Positive and Negative Syndrome Scale, severity of illness score on the Clinical
      Global Impression (CGI), and total score and psychosis cluster score on the Brief
      Psychiatric Rating Scale (BPRS). RESULTS: Significantly greater improvement in
      all primary efficacy variables was seen in the group receiving haloperidol than
      in the group receiving placebo at 6 weeks (endpoint analyses), indicating the
      validity of the study. The group receiving the NK(3) antagonist showed
      significantly greater improvement over baseline than the group receiving placebo
      as measured by Positive and Negative Syndrome Scale total score, CGI severity of
      illness score, and BPRS psychosis cluster score. Reductions in the Positive and
      Negative Syndrome Scale total and negative scores in the group receiving the 5
      HT(2A/2C) antagonist were significantly larger than those in the group receiving
      placebo. The improvements in psychopathology produced by the NK(3) and 5
      HT(2A/2C) antagonists were smaller than those produced by haloperidol, although
      the response to the NK(3) antagonist was positively correlated with plasma
      levels. The groups receiving the CB(1) and NTS(1) antagonists did not differ from
      the group receiving placebo on any outcome measure. All investigational drugs
      were well tolerated. CONCLUSIONS: The novel design used in this study permitted
      the use of a smaller number of patients receiving placebo to test the efficacy of
      the four novel compounds. The NK(3) and 5-HT(2A/2C) antagonists showed evidence
      of efficacy in the treatment of schizophrenia and schizoaffective disorder. Study
      limitations preclude a definitive conclusion on the efficacy of CB(1) and NTS(1)
      antagonists in the treatment of schizophrenia. Further study of these two
      promising nondopaminergic mechanisms to treat schizophrenia and schizoaffective
      disorder appears indicated.

PMID- 15169686
TI  - Comparative effect of atypical and conventional antipsychotic drugs on
      neurocognition in first-episode psychosis: a randomized, double-blind trial of
      olanzapine versus low doses of haloperidol.
AB  - OBJECTIVE: The effect of antipsychotic medication on neurocognitive function
      remains controversial, especially since most previous work has compared the
      effects of novel antipsychotic medications with those of high doses of
      conventional medications. This study compares the neurocognitive effects of
      olanzapine and low doses of haloperidol in patients with first-episode psychosis.
      METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder,
      or schizophreniform disorder (N=167) were randomly assigned to double-blind
      treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean
      modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The
      patients were assessed with a battery of neurocognitive tests at baseline and 12
      weeks after beginning treatment. RESULTS: An unweighted neurocognitive composite
      score, composed of measures of verbal fluency, motor functions, working memory,
      verbal memory, and vigilance, improved significantly with both haloperidol and
      olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant
      difference between groups). A weighted composite score developed from a principal
      component analysis of the same measures improved to a significantly greater
      degree with olanzapine, compared with haloperidol. Anticholinergic use,
      extrapyramidal symptoms, and estimated IQ had little effect on the statistical
      differentiation of the medications, although duration of illness had a modest
      effect. The correlations of cognitive improvement with changes in clinical
      characteristics and with side effects of treatment were significant for patients
      who received haloperidol but not for patients who received olanzapine.
      CONCLUSIONS: Olanzapine has a beneficial effect on neurocognitive function in
      patients with a first episode of psychosis. However, in a comparison of the
      effects of olanzapine and low doses of haloperidol, the difference in benefit is
      small.

PMID- 15169687
TI  - Neuropsychological dysfunction in antipsychotic-naive first-episode unipolar
      psychotic depression.
AB  - OBJECTIVE: The profile of neuropsychological impairment associated with unipolar
      psychotic depression remains unclear. The authors used a neuropsychological test
      battery to characterize the neuropsychiatric profile of patients with unipolar
      psychotic depression, relative to that of patients with nonpsychotic unipolar
      depression, patients with schizophrenia, and healthy comparison subjects. METHOD:
      Study subjects included antipsychotic-naive patients with a first episode of
      psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated
      patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive
      patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81).
      Groups were matched on age, sex, race, education, parental socioeconomic status,
      and estimated premorbid intelligence. Psychotic patients were followed clinically
      for 2 years to confirm diagnosis. All participants completed a standard
      neuropsychological battery, including tests of general intelligence, executive
      function, attention, verbal memory, motor skills, and visual-spatial perception.
      RESULTS: Patients with psychotic depression had a pattern of neuropsychological
      dysfunction that was similar to but less severe than that of patients with
      schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a
      neuropsychological profile that was similar to that of healthy individuals but
      that included mild dysfunction on tests of attention. Neuropsychological test
      performance was generally independent of acute clinical symptoms, but some
      pairwise group differences were attenuated by covariation for symptom severity.
      CONCLUSIONS: The similar neuropsychological profiles for schizophrenia and
      psychotic depression suggest that these psychotic disorders may have common
      pathophysiological features. The dramatic differences in performance between the
      patients with psychotic depression and those with nonpsychotic depression point
      to a marked distinction in neurocognitive function associated with the expression
      of psychosis in depressed patients.

PMID- 15169688
TI  - Event-related fMRI of frontotemporal activity during word encoding and
      recognition in schizophrenia.
AB  - OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory
      deficits in schizophrenia during word encoding and retrieval. This study examined
      neural substrates of memory in an analysis that controlled for successful
      retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional
      magnetic resonance imaging (fMRI) was used to measure brain activation during
      word encoding and recognition in 14 patients with schizophrenia and 15 healthy
      comparison subjects. An unbiased multiple linear regression procedure was used to
      model the BOLD response, and task effects were detected by contrasting the signal
      before and after stimulus onset. RESULTS: Patients attended during encoding and
      had unimpaired reaction times and normal response biases during recognition, but
      they had lower recognition discriminability scores, compared with the healthy
      subjects. Analysis of contrasts was restricted to correct items. Previous
      findings of a deficit in bilateral prefrontal cortex activation during encoding
      in patients were reproduced, but patients showed greater parahippocampal
      activation rather than deficits in temporal lobe activation. During recognition,
      left dorsolateral prefrontal cortex activation was lower in the patients and
      right anterior prefrontal cortex activation was preserved, as in the authors'
      previous study using positron emission tomography. Successful retrieval was
      associated with greater right dorsolateral prefrontal cortex activation in the
      comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal,
      middle temporal, and inferior parietal regions were more active in the patients
      during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex
      underactivation and parahippocampal overactivation in the patients suggests that
      functional connectivity of dorsolateral prefrontal and temporal-limbic structures
      is disrupted by schizophrenia. This disruption may be reflected in the memory
      strategies of patients with schizophrenia, which include reliance on rote
      rehearsal rather than associative semantic processing.

PMID- 15169690
TI  - Cerebellar, prefrontal cortex, and thalamic volumes over two time points in
      adolescent-onset schizophrenia.
AB  - OBJECTIVE: Structural and functional studies implicate multiple brain lesions as
      a basis for a functional dysconnectivity underlying the cognitive and symptom
      profiles in schizophrenia. The aim of this study was to examine the hypothesis
      that early-onset schizophrenia is associated with structural abnormalities in the
      prefrontal cortex, thalamus, and cerebellum, compatible with a dysconnectivity
      syndrome. METHOD: Two magnetic resonance imaging scans of 16 patients and 16
      normal comparison subjects were undertaken on average 2 to 3 years apart. The
      participants were all from a defined geographic area in the United Kingdom with a
      population of 2.5 million. RESULTS: In comparison to the normal adolescents, the
      schizophrenic subjects demonstrated low prefrontal cortex and thalamic volumes.
      The relatively large difference in prefrontal and thalamic volumes in these
      adolescents with schizophrenia implies a more severe disease process than in
      adult subjects. CONCLUSIONS: The thalamic and frontal lobe findings provide
      preliminary, supportive structural evidence for a neurodevelopmental basis for a
      dysconnectivity syndrome, although the cerebellar findings were inconclusive.

PMID- 15169689
TI  - Low dopamine d(2) receptor binding in subregions of the thalamus in
      schizophrenia.
AB  - OBJECTIVE: Several structural and functional brain imaging studies have pointed
      to a disturbance of thalamic subnuclei in patients with schizophrenia. The
      dopamine hypothesis of schizophrenia has, however, not been thoroughly examined
      in terms of this complex structure, which has connections with most brain regions
      of central interest in schizophrenia research. The aim of the present study was
      to examine dopamine D(2) receptor binding in subregions of the thalamus in
      patients with schizophrenia. METHOD: The authors used positron emission
      tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor
      binding in thalamic subregions of 10 drug-naive patients with schizophrenia.
      Binding potential was calculated by the reference tissue method and used as an
      index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy
      subjects. Subregions of interest were defined on individual magnetic resonance
      images using a percentage-based operational approach. Clinical symptoms were
      rated by using the Brief Psychiatric Rating Scale (BPRS). RESULTS: The
      [(11)C]FLB457 binding potential was lower in the central medial and posterior
      subregions of the thalamus in patients with schizophrenia. At a functional level,
      there was a significant negative correlation between binding potential and BPRS
      positive symptom scores. CONCLUSIONS: The subregions with low D(2) receptor
      binding comprise primarily the dorsomedial nucleus and pulvinar, two important
      components in circuitries previously suggested in the pathophysiology of
      schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions
      might be a mechanism underlying positive symptoms in schizophrenia.

PMID- 15169691
TI  - Prospective study of neurological abnormalities in offspring of women with
      psychosis: birth to adulthood.
AB  - OBJECTIVE: The authors prospectively investigated neurological abnormalities in
      75 young adult offspring of mothers with psychotic disorders and 91 offspring of
      comparison mothers with no psychosis history. They also studied the stability of
      these abnormalities from birth to adulthood. METHOD: Neurological abnormalities
      were previously studied in infancy and at 6 years of age. In this study, they
      were blindly assessed with a comprehensive neurological assessment scale at a
      mean age of 22.4 years in a 93.3% effective follow-up of the sample. RESULTS: In
      relation to the comparison subjects (N=88) and offspring of mothers with
      affective psychosis (N=22), the adult offspring of mothers with schizophrenia
      (N=28) had significantly more neurological abnormalities. More soft signs,
      primitive reflexes, involuntary movements, and cranial nerve abnormalities
      characterized a subgroup (32%) among these offspring. The offspring of mothers
      with affective psychosis were not different from comparison subjects. The
      extension of schizophrenia and affective psychosis risk groups to include
      additional maternal "spectrum cases" (N=10 and N=14, respectively) generally
      yielded similar results. Neurological abnormalities at 22 years were
      significantly associated with neurological abnormalities at age 6, but not in
      infancy, among the total high-risk group, offspring of mothers with
      schizophrenia, and comparison offspring. CONCLUSIONS: High levels of neurological
      abnormalities are found in a substantial proportion of offspring of mothers with
      schizophrenia but not offspring of mothers with affective psychosis. This
      suggests that familial risk for schizophrenia is associated with
      neurodevelopmental disturbance that is manifest throughout life and belongs to a
      different biological continuum from that of affective psychosis.

PMID- 15169692
TI  - Cerebral glucose metabolism in obsessive-compulsive hoarding.
AB  - OBJECTIVE: Compulsive hoarding and saving symptoms, found in many patients with
      obsessive-compulsive disorder (OCD), are part of a discrete clinical syndrome
      that includes indecisiveness, disorganization, perfectionism, procrastination,
      and avoidance and has been associated with poor response to medications and
      cognitive behavior therapy. The authors sought to identify cerebral metabolic
      patterns specifically associated with the compulsive hoarding syndrome using
      positron emission tomography (PET). METHOD: [(18)F]Fluorodeoxyglucose PET scans
      were obtained for 45 adult subjects who met DSM-IV criteria for OCD (12 of whom
      had compulsive hoarding as their most prominent OCD symptom factor) and 17 normal
      comparison subjects. All subjects had been free of psychotropic medication for at
      least 4 weeks. Regional cerebral glucose metabolism was compared between the
      groups. RESULTS: In relation to the comparison subjects, the patients with
      compulsive hoarding syndrome had significantly lower glucose metabolism in the
      posterior cingulate gyrus and cuneus, whereas the nonhoarding OCD patients had
      significantly higher glucose metabolism in the bilateral thalamus and caudate. In
      relation to nonhoarding OCD patients, compulsive hoarders had significantly lower
      metabolism in the dorsal anterior cingulate gyrus. Across all OCD patients,
      hoarding severity was negatively correlated with glucose metabolism in the dorsal
      anterior cingulate gyrus. CONCLUSIONS: OCD patients with the compulsive hoarding
      syndrome had a different pattern of cerebral glucose metabolism than nonhoarding
      OCD patients and comparison subjects. Obsessive-compulsive hoarding may be a
      neurobiologically distinct subgroup or variant of OCD whose symptoms and poor
      response to anti-obsessional treatment are mediated by lower activity in the
      cingulate cortex.

PMID- 15169693
TI  - Brain structural abnormalities in psychotropic drug-naive pediatric patients with
      obsessive-compulsive disorder.
AB  - OBJECTIVE: The authors investigated structural abnormalities in brain regions
      comprising cortical-striatal-thalamic-cortical loops in pediatric patients with
      obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus,
      putamen, and globus pallidus and gray and white matter volumes of the anterior
      cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm
      magnetic resonance images from 23 psychotropic drug-naive pediatric patients with
      OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12
      male subjects and 15 female subjects). RESULTS: Patients had smaller globus
      pallidus volumes than healthy volunteers, but the two groups did not differ in
      volumes of the caudate nucleus, putamen, or frontal white matter regions.
      Compared to healthy volunteers, patients had more total gray matter in the
      anterior cingulate gyrus but not the superior frontal gyrus. Total anterior
      cingulate gyrus volume correlated significantly and positively with globus
      pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These
      findings provide evidence of smaller globus pallidus volume in patients with OCD
      without the potentially confounding effects of prior psychotropic drug exposure.
      Volumetric abnormalities in the anterior cingulate gyrus appear specific to the
      gray matter in OCD, at least at the gross anatomic level, and are consistent with
      findings of functional neuroimaging studies that have reported anterior cingulate
      hypermetabolism in the disorder.

PMID- 15169694
TI  - Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: This study evaluated the efficacy and safety of risperidone
      monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV
      bipolar I disorder experiencing an acute manic episode (baseline Young Mania
      Rating Scale score >/==" BORDER="0">20) were randomly assigned to 3 weeks of
      treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary
      efficacy measure was the mean baseline-to-endpoint change in total score on the
      Young Mania Rating Scale. Secondary efficacy measures included the Clinical
      Global Impression (CGI) severity rating and scores on the Montgomery-Asberg
      Depression Rating Scale, Positive and Negative Syndrome Scale, and Global
      Assessment Scale (GAS). Safety assessments consisted of monitoring adverse
      events, vital signs, electrocardiogram and laboratory results, and scores on the
      Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment
      with either risperidone (N=134) or placebo (N=125). The mean modal dose of
      risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total
      score (adjusted for covariates) was significantly greater in the risperidone than
      in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8
      [SD=9.5], respectively), with significant between-group differences seen as early
      as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8];
      change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time
      points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg
      Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also
      significantly greater among patients receiving risperidone than those given
      placebo. The most common adverse event reported among risperidone patients was
      somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly
      greater in patients receiving risperidone, mean total and subscale scores were
      low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than
      placebo in the treatment of acute mania and demonstrated a rapid onset of action.
      Risperidone was well tolerated by patients in this study.

PMID- 15169695
TI  - Pooled analysis of antidepressant levels in lactating mothers, breast milk, and
      nursing infants.
AB  - OBJECTIVE: The available data on antidepressant levels in nursing infants were
      analyzed in order to calculate average infant drug levels and determine what
      factors influence plasma drug levels in breast-feeding infants of mothers treated
      with antidepressants. METHOD: Electronic searches of MEDLINE, PreMEDLINE, Current
      Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed
      by bibliographic searches identified 67 relevant studies (two unpublished). By
      consensus the authors identified 57 studies of maternal plasma, breast milk,
      and/or infant plasma antidepressant levels from nursing mother-infant pairs,
      measured by liquid chromatography. RESULTS: Infants with recent prenatal exposure
      and symptomatic infants included in case reports were analyzed separately. Infant
      plasma levels were standardized against the average maternal level for each drug.
      The average infant-maternal plasma ratio was calculated for each drug, and
      correlations of infant plasma level to maternal dose, maternal plasma level, and
      breast milk level were calculated. Nortriptyline, paroxetine, and sertraline
      usually produce undetectable infant levels. Of drugs currently used, fluoxetine
      produces the highest proportion (22%) of infant levels that are elevated above
      10% of the average maternal level. Based on smaller numbers, the data on
      citalopram indicate that it produces elevated levels in 17% of infants. The milk
      to-plasma ratios for 11 antidepressants had a statistically significant negative
      association with the percentage of the drug bound to protein. CONCLUSIONS:
      Nortriptyline, paroxetine, and sertraline may be preferred choices in breast
      feeding women. Minimizing the maternal dose may be helpful with citalopram.
      Current data do not support monitoring breast milk levels in individual patients.
      Future researchers should report maternal, breast milk, and infant antidepressant
      levels along with other appropriate variables.

PMID- 15169696
TI  - A randomized, placebo-controlled trial of citalopram for the treatment of major
      depression in children and adolescents.
AB  - OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor
      citalopram suggest that this agent is effective and safe for the treatment of
      depressive symptoms in children and adolescents. The current study investigated
      the efficacy and safety of citalopram compared with placebo in the treatment of
      pediatric patients with major depression. METHOD: An 8-week, randomized, double
      blind, placebo-controlled study compared the safety and efficacy of citalopram
      with placebo in the treatment of children (ages 7-11) and adolescents (ages 12
      17) with major depressive disorder. Diagnosis was established with the Schedule
      for Affective Disorders and Schizophrenia for School-Age Children-Present and
      Lifetime Version. Patients (N=174) were treated initially with placebo or 20
      mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4
      if clinically indicated. The primary outcome measure was score on the Children's
      Depression Rating Scale-Revised; the response criterion was defined as a score of
      < or =28. RESULTS: The overall mean citalopram dose was approximately 24 mg/day.
      Mean Children's Depression Rating Scale-Revised scores decreased significantly
      more from baseline in the citalopram treatment group than in the placebo
      treatment group, beginning at week 1 and continuing at every observation point to
      the end of the study (effect size=2.9). The difference in response rate at week 8
      between placebo (24%) and citalopram (36%) also was statistically significant.
      Citalopram treatment was well tolerated. Rates of discontinuation due to adverse
      events were comparable in the placebo and citalopram groups (5.9% versus 5.6%,
      respectively). Rhinitis, nausea, and abdominal pain were the only adverse events
      to occur with a frequency exceeding 10% in either treatment group. CONCLUSIONS:
      In this population of children and adolescents, treatment with citalopram reduced
      depressive symptoms to a significantly greater extent than placebo treatment and
      was well tolerated.

PMID- 15169697
TI  - Seasonal variation in mood in African American college students in the
      Washington, D.C., metropolitan area.
AB  - OBJECTIVE: The authors attempted to estimate the occurrence, frequency, and
      pattern (winter versus summer) of seasonal affective disorder in African American
      college students. They hypothesized that winter seasonal affective disorder would
      be more prevalent than summer seasonal affective disorder. METHOD: Undergraduate
      and graduate college students who identified themselves as African Americans
      living in the Washington, D.C., metropolitan area were invited to participate in
      the study. The Seasonal Pattern Assessment Questionnaire was used to calculate a
      global seasonality score and to estimate the frequency of seasonal affective
      disorder and subsyndromal seasonal affective disorder. The frequency of the
      summer versus winter pattern of seasonality of seasonal affective disorder was
      compared by using multinomial probability distribution tests. The effects of
      gender and the awareness of seasonal affective disorder were evaluated with a two
      way analysis of variance. RESULTS: Of 646 students who were invited to
      participate, 597 returned the questionnaires, and 537 (83.1%) fully completed
      them. Winter seasonal affective disorder was significantly more prevalent than
      summer seasonal affective disorder. The mean global seasonality score was 8.3
      (SD=5.3). The majority of the subjects (80%) were not aware of the existence of
      seasonal affective disorder. CONCLUSIONS: The authors found that the frequency,
      magnitude, and pattern of seasonality of mood in African American students were
      similar to those previously reported in the general population at similar
      latitude, but that awareness of the existence of seasonal affective disorder, a
      condition with safe and effective treatment options, was lower.

PMID- 15169698
TI  - Depression and other mental health diagnoses increase mortality risk after
      ischemic stroke.
AB  - OBJECTIVE: Poststroke depression has been linked to higher mortality after
      stroke. However, the effect of other mental health conditions on poststroke
      mortality has not been examined. The objective of this study was to evaluate the
      effect of poststroke depression and other mental health diagnoses on mortality
      after ischemic stroke. METHOD: The authors examined a national cohort of veterans
      hospitalized after an ischemic stroke at any U.S. Department of Veterans Affairs
      (VA) medical center from 1990 to 1998. Demographic, admission, and all-cause
      mortality data were abstracted from VA administrative databases. Chronic
      conditions present at discharge and new poststroke depression and other mental
      health diagnoses within 3 years after the stroke were identified with ICD-9
      codes. Mortality hazard ratios were modeled by using Cox regression models.
      RESULTS: A total of 51,119 patients hospitalized after an ischemic stroke who
      survived beyond 30 days afterward were identified; 2,405 (5%) received a
      diagnosis of depression, and 2,257 (4%) received another mental health diagnosis
      within 3 years of their stroke. Patients with poststroke depression were younger,
      more often white, and less likely to be alive at the end of the 3-year follow-up
      period. Both poststroke depression (hazard ratio=1.13, 95% CI=1.06-1.21) and
      other mental health diagnoses (hazard ratio=1.13, 95% CI=1.07-1.22) independently
      increased the hazard for death even after other chronic conditions were
      controlled. CONCLUSIONS: Despite being younger and having fewer chronic
      conditions, a higher 3-year mortality risk was seen in patients with poststroke
      depression and other mental health diagnoses after hospitalization for an
      ischemic stroke. The biological and psychosocial mechanisms driving this greater
      risk should be further explored, and the effect of depression treatment on
      mortality after stroke should be tested.

PMID- 15169699
TI  - Neuropathological study of the dorsal raphe nuclei in late-life depression and
      Alzheimer's disease with and without depression.
AB  - OBJECTIVE: Few studies have examined pathological changes in serotonergic neurons
      in depression, particularly in elderly patients and in elderly patients in which
      depression occurs in dementia. The authors hypothesized that greater
      neurofibrillary pathology and fewer serotonergic neurons would be found in the
      dorsal raphe nuclei in depressed elderly subjects, compared with nondepressed
      elderly subjects, and in Alzheimer's disease patients with depression, compared
      to Alzheimer's disease patients without depression. METHOD: In a postmortem
      study, immunocytochemistry and two-dimensional image analysis were used to
      measure neuronal density and neuritic pathology in serotonergic neurons in the
      dorsal raphe nuclei of elderly subjects with primary major depression (N=14),
      elderly Alzheimer's disease patients with (N=8) and without (N=7) comorbid
      depression, and nondepressed elderly comparison subjects (N=10). RESULTS: No
      differences in neuritic pathology or neuronal density were found between the
      subjects with primary major depression and the nondepressed comparison subjects.
      The Alzheimer's disease subjects showed markedly fewer serotonergic neurons and
      associated higher levels of neuritic pathology, compared with the subjects with
      primary depression and the nondepressed comparison subjects, but the Alzheimer's
      disease subjects with comorbid major depression did not differ from the
      Alzheimer's disease subjects without depression on these measures. CONCLUSIONS:
      The study found no evidence of a loss of serotonergic neurons or of neuritic
      pathology in the dorsal raphe nuclei in older people with depression, with or
      without comorbid Alzheimer's disease. These findings suggest that if serotonergic
      dysfunction occurs in older depressed subjects, it is not due to neuronal loss in
      the brainstem. Pathophysiological changes may lie elsewhere, such as in the
      frontal-subcortical circuits.

PMID- 15169700
TI  - Association of utilization management and treatment plan modifications among
      practicing U.S. psychiatrists.
AB  - OBJECTIVE: This study examined the relationship between utilization management
      techniques and psychiatrists' treatment plan modifications. METHOD: Nationally
      representative data on 1,843 patients treated by 615 psychiatrists participating
      in the American Psychiatric Institute for Research and Education's Practice
      Research Network were used to examine the demographic and clinical
      characteristics of patients whose care was subjected to utilization management
      and to assess the association between utilization management and psychiatrists'
      treatment plan modifications. RESULTS: Approximately half of all patients had
      treatment that was subject to utilization management (52.6%). For the patients
      whose treatment was not subject to utilization management, 15.5% had their
      treatment plan changed compared to the 31.5% who were subject to utilization
      management. Overall, after adjustment for differences in patients, settings, and
      psychiatrist characteristics, the patients subject to utilization management were
      2.6 times more likely to have their treatment changed than the patients who were
      not subject to utilization management. These patients were 3.7 times more likely
      to have their type of treatment changed and 2.3 times more likely to have their
      frequency or number of visits changed. Psychiatrists in individual practice
      settings and those with nonsalaried income sources were more likely to modify
      treatment decisions for their patients when subject to utilization management.
      CONCLUSIONS: The presence of utilization management is highly associated with
      changes in psychiatrists' treatment decisions. When compared to evidence-based
      treatment recommendations, these changes seem likely to result in less than
      optimal care.

PMID- 15169701
TI  - New evidence of association between COMT gene and prefrontal neurocognitive
      function in healthy individuals from sibling pairs discordant for psychosis.
AB  - OBJECTIVE: Using a sample of sibling pairs discordant for psychosis, the authors
      attempted to replicate the findings of previous studies suggesting that the
      functional genetic polymorphism Val158Met in the catechol O-methyltransferase
      (COMT) gene influences prefrontal cognitive function and increases the risk for
      schizophrenia. METHOD: Eighty-nine sibling pairs discordant for psychosis were
      genotyped for this polymorphism and were assessed with the Wisconsin Card Sorting
      Test, a measure of prefrontal function. Additionally, the preferential
      transmission of alleles for this polymorphism was analyzed in a sample of 89
      nuclear families in order to examine the genetic association. RESULTS: In the
      healthy siblings, a linear relationship was seen in which performance on the
      Wisconsin Card Sorting Test was associated in an allele dosage fashion with COMT
      genotype (i.e., fewer perseverative errors with higher number of methionine
      alleles). However, this association was not observed in patients. Furthermore, no
      evidence of genetic association with psychosis was detected. CONCLUSIONS: These
      results seem to confirm the role of COMT genotype in the modulation of executive
      functions related to frontal lobe function in healthy individuals but not in
      schizophrenia patients.

PMID- 15169702
TI  - Atypical antipsychotics and risk of cerebrovascular accidents.
AB  - OBJECTIVE: Randomized controlled trials have suggested that at least one atypical
      antipsychotic may be associated with an increased risk of stroke in older people
      with dementia. This study examined the association between atypical antipsychotic
      use and stroke in the elderly. METHOD: The authors conducted a retrospective
      population-based cohort study of patients over the age of 66 by linking
      administrative health care databases. Three cohorts-users of typical
      antipsychotics, risperidone, and olanzapine-were identified and compared.
      RESULTS: Subjects treated with typical antipsychotics (N=1,015) were compared
      with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based
      estimates adjusted for covariates hypothesized to be associated with stroke risk
      revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4
      (95% CI=0.7-2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use
      were not associated with a statistically significant increased risk of stroke
      compared with typical antipsychotic use.

PMID- 15169703
TI  - 3-T proton MRS investigation of glutamate and glutamine in adolescents at high
      genetic risk for schizophrenia.
AB  - OBJECTIVE: Glutamate and glutamine were examined in vivo in nonpsychotic
      adolescents at high genetic risk for schizophrenia by using 3-T proton magnetic
      resonance spectroscopy ((1)H-MRS). METHOD: Spectra from the right medial frontal
      lobe of 20 adolescents who had a parent with schizophrenia (high-risk group; mean
      age=16.4 years) were compared with spectra obtained from adolescent offspring of
      parents with no history of schizophrenia (low-risk group; mean age=16.7 years).
      RESULTS: Glutamate/glutamine was significantly higher in the adolescents at high
      genetic risk for schizophrenia than in the low-risk offspring. Age, premorbid
      adjustment scale scores, and other (1)H-MRS metabolites did not differ between
      groups. Global Assessment of Functioning Scale scores and socioeconomic status
      were lower in the high-risk group. DISCUSSION: The finding of glutamate/glutamine
      abnormalities in a group of subjects at high genetic risk for schizophrenia lends
      support for both the glutamate dysfunction and neurodevelopmental hypotheses for
      schizophrenia.

PMID- 15169704
TI  - Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a
      proton magnetic resonance spectroscopic imaging study.
AB  - OBJECTIVE: Few neuroimaging studies of generalized anxiety disorder have been
      conducted. The present study used proton magnetic resonance spectroscopy to
      assess concentrations of N-acetylaspartate, often considered a marker of neuronal
      viability, in generalized anxiety disorder patients. METHOD: N
      Acetylaspartate/creatine resonance ratios were measured in the left and right
      dorsolateral prefrontal cortex and hippocampus of 15 medication-free generalized
      anxiety disorder patients and 15 age- and sex-matched healthy volunteers.
      RESULTS: Generalized anxiety disorder patients had a 16.5% higher N
      acetylaspartate/creatine ratio in the right dorsolateral prefrontal cortex
      compared with healthy participants; 13 of 15 matched patient-comparison subject
      pairs displayed a difference in this direction. In addition, generalized anxiety
      disorder patients reporting childhood abuse had lower N-acetylaspartate/creatine
      ratios in the right dorsolateral prefrontal cortex than did nonabused patients.
      Metabolite differences were not detected in other regions. CONCLUSIONS:
      Generalized anxiety disorder is associated with asymmetric increases in the N
      acetylaspartate/creatine ratio, a suggested marker of neuronal viability, in the
      prefrontal cortex. The findings also support prior research linking childhood
      abuse to reduced neuronal viability.

PMID- 15169705
TI  - Reduced superior temporal gyrus volume in young offspring of patients with
      schizophrenia.
AB  - OBJECTIVE: The superior temporal gyrus, a heteromodal auditory and language
      association cortex, has been found to be smaller in patients with schizophrenia
      than in normal subjects. However, genetic and/or neurodevelopmental underpinnings
      of superior temporal gyrus alterations are unknown. Nonpsychotic children with
      greater genetic risk for schizophrenia exhibit language deficits. The authors
      studied the superior temporal gyrus in nonpsychotic children at risk for
      schizophrenia. METHOD: Magnetic resonance imaging was used to measure the right
      and left superior temporal gyrus of 29 young nonpsychotic subjects who had a
      parent with schizophrenia and 27 age- and sex-matched comparison subjects who had
      no family psychiatric history. RESULTS: After controlling for age and
      intracranial volume, the authors found that the volumes of the right and left
      superior temporal gyrus of the subjects at risk for schizophrenia were
      significantly smaller than those of the comparison subjects. Comparison subjects,
      but not at-risk subjects, showed an inverse correlation between age and left
      superior temporal gyrus volume. CONCLUSIONS: These findings provide new evidence
      that superior temporal gyrus abnormalities may result from genetically mediated
      developmental deviance reflecting greater susceptibility to schizophrenia.
      Further studies and follow-up will lead to greater understanding of the role of
      the superior temporal gyrus in the premorbid vulnerability to schizophrenia.

PMID- 15169707
TI  - Delirium from valproic acid with lamotrigine.

PMID- 15169706
TI  - Weight and leptin changes among risperidone-treated youths with autism: 6-month
      prospective data.
AB  - OBJECTIVE: The authors examined the developmental impact and temporal
      characteristics of risperidone-associated weight change. METHOD: Weight change
      was measured for 63 children and adolescents with autism treated with risperidone
      for 6 months. Change in serum leptin levels after 2 months was examined as a
      predictor of final weight gain in mixed regression models that controlled for
      site, gender, age, and risperidone dose. RESULTS: Age- and gender-standardized
      weight increased after 6 months of treatment (gross: mean=5.6 kg [SD=3.9];
      standardized: mean=0.6 z [SD=0.5]) and was positively correlated with weight
      gained after 1 month. Change in leptin levels after 2 months of treatment (mean=
      0.3 ng/ml, SD=6.2) (N=48) did not predict final weight gain. CONCLUSIONS: Chronic
      risperidone exposure in children with autism causes weight gain in excess of
      developmentally expected norms that follows a curvilinear trajectory and
      decelerates over time. Serum leptin change does not reliably predict risperidone
      associated weight gain.

PMID- 15169708
TI  - Depression and Devic's syndrome.

PMID- 15169709
TI  - Serotonin syndrome with tramadol and citalopram.

PMID- 15169710
TI  - Venlafaxine and sour date nut.

PMID- 15169711
TI  - Polyuria after olanzapine overdose.

PMID- 15169712
TI  - Oxcarbazepine as an adjunct for schizophrenia.

PMID- 15169713
TI  - Pitfalls of meta-analyses.

PMID- 15169714
TI  - Elevated homocysteine levels in schizophrenia.

PMID- 15169716
TI  - On chronic fatigue syndrome.

PMID- 15169718
TI  - On chronic fatigue syndrome.

PMID- 15169719
TI  - Genetic linkage for schizophrenia?

PMID- 15169722
TI  - Classification of catatonia.

PMID- 15169720
TI  - Genetic linkage for schizophrenia?

PMID- 15169734
TI  - Sertraline and the Cheshire cat in geriatric depression.

PMID- 15169735
TI  - Perioperative myocardial injury: individual and population implications.

PMID- 15169736
TI  - Pacemakers and defibrillators: anaesthetic implications.

PMID- 15169737
TI  - Pharmacokinetics of rectal tramadol in postoperative paediatric patients.
AB  - BACKGROUND: Postoperative analgesia in children may be improved by using
      tramadol. The pharmacokinetics of rectal tramadol in young children were
      therefore investigated. METHODS: The pharmacokinetics of rectal tramadol and its
      active metabolite were studied in 12 young children (age: 1-6 yr)
      postoperatively. On the basis of these data, a population model was constructed.
      Using this model, the pharmacokinetics of different doses of tramadol were
      calculated. RESULTS: The pharmacokinetics of rectal tramadol could be adequately
      described by a one-compartment model. The pharmacokinetic parameters derived from
      the model indicate that a low variability was present. Elimination half-life was
      4.3 (0.2) h (sem) and the apparent clearance was 16.4 (1.5) litre h(-1) (sem).
      CONCLUSIONS: The study showed that after rectal administration, tramadol is
      absorbed at a reasonable rate and with a low inter-individual variability in
      small children. The data also suggested that a rectal dose of tramadol 1.5-2.0 mg
      kg(-1) is therapeutic.

PMID- 15169739
TI  - Physicochemical properties of neuromuscular blocking agents and their impact on
      the pharmacokinetic-pharmacodynamic relationship.
AB  - BACKGROUND: Among the factors influencing the onset of action of neuromuscular
      blocking agents (NMBA), the potency (EC50) and the rate of equilibration between
      blood and the effect compartment (k(e0)) have been highlighted. Although these
      descriptors are intrinsically influenced by the physicochemical characteristics
      of the drug, the impact of lipid solubility, molecular weight and protein binding
      on pharmacokinetic-pharmacodynamic (PK-PD) descriptors has not been established
      for most NMBA. METHODS: The octanol/phosphate buffer distribution coefficients
      (logD) of various NMBA (vecuronium, rocuronium, mivacurium isomers (cis-cis, cis
      trans and trans-trans), doxacurium, cisatracurium, atracurium, succinylcholine)
      were determined. The free fraction for each drug was measured using an
      ultrafiltration technique. PK-PD descriptors were obtained from selected clinical
      studies. Correlations between physicochemical parameters (including molecular
      weight) and PK-PD descriptors were assessed by linear or multiple linear
      regression. RESULTS: A wide range of log D (-4.15 for succinylcholine to 0.75 for
      vecuronium) and free fraction (from 31% for vecuronium to 80% for
      succinylcholine) is observed for NMBA. Molecular weight combined with either
      lipid solubility (r2=0.70; P=0.001) or free fraction (r2=0.84; P<0.001) were
      highly correlated with potency, while for k(e0) a greater degree of correlation
      was obtained when both lipid solubility and free fraction (r2=0.74; P=0.002) were
      included. CONCLUSIONS: The basic characteristics of NMBAs, namely, molecular
      weight, lipid solubility and protein binding, are strongly associated with the
      kinetics of the drug response.

PMID- 15169738
TI  - Respiratory and haemodynamic effects of acute postoperative pain management:
      evidence from published data.
AB  - BACKGROUND: This study examines the evidence from published data concerning the
      adverse respiratory and haemodynamic effects of three analgesic techniques after
      major surgery; i.m. analgesia, patient-controlled analgesia (PCA), and epidural
      analgesia. METHODS: A MEDLINE search of the literature was conducted for
      publications concerned with the management of postoperative pain. Information
      relating to variables indicative of respiratory depression and of hypotension was
      extracted from these studies. Over 800 original papers and reviews were
      identified. Of these papers, 212 fulfilled the inclusion criteria but only 165
      provided usable data on adverse effects. Pooled data obtained from these studies,
      which represent the experience of a total of nearly 20,000 patients, form the
      basis of this study. RESULTS: There was considerable variability between studies
      in the criteria used for defining respiratory depression and hypotension. The
      overall mean (95% CI) incidence of respiratory depression of the three analgesic
      techniques was: 0.3 (0.1-1.3)% using requirement for naloxone as an indicator;
      1.1 (0.7-1.7)% using hypoventilation as an indicator; 3.3 (1.4-7.6)% using
      hypercarbia as an indicator; and 17.0 (10.2-26.9)% using oxygen desaturation as
      an indicator. For i.m. analgesia, the mean (95% CI) reported incidence of
      respiratory depression varied between 0.8 (0.2-2.5) and 37.0 (22.6-45.9)% using
      hypoventilation and oxygen desaturation, respectively, as indicators. For PCA,
      the mean (95% CI) reported incidence of respiratory depression varied between 1.2
      (0.7-1.9) and 11.5 (5.6-22.0)%, using hypoventilation and oxygen desaturation,
      respectively, as indicators. For epidural analgesia, the mean (95% CI) reported
      incidence of respiratory depression varied between 1.1 (0.6-1.9) and 15.1 (5.6
      34.8)%, using hypoventilation and oxygen desaturation, respectively, as
      indicators. The mean (95% CI) reported incidence of hypotension for i.m.
      analgesia was 3.8 (1.9-7.5)%, for PCA 0.4 (0.1-1.9)%, and for epidural analgesia
      5.6 (3.0-10.2)%. Whereas the incidence of respiratory depression decreased over
      the period 1980-99, the incidence of hypotension did not. CONCLUSIONS: Assuming a
      mixture of analgesic techniques, Acute Pain Services should expect an incidence
      of respiratory depression, as defined by a low ventilatory frequency, of less
      than 1%, and an incidence of hypotension related to analgesic technique of less
      than 5%.

PMID- 15169740
TI  - In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)
      induced vasoconstriction in human internal mammary artery.
AB  - BACKGROUND: Hypertension is a major problem in the perioperative period of
      cardiac and non-cardiac surgery. The vascular endothelium plays a crucial role in
      modulating vascular tone by producing vasodilators as well as vasoconstrictors.
      Thromboxane A2 (TxA2), a prototypical vasoconstrictor produced by endothelium and
      platelets, may play an important role in the pathogenesis of hypertension and
      subsequent ischaemic events. Although multiple drugs are currently available to
      treat perioperative hypertension, there is a paucity of data comparing these
      agents. Therefore, we examined the in vitro vascular effects of commonly used
      antihypertensive drugs on human internal mammary artery (IMA) segments. METHODS:
      Relaxation responses to adenosine (a nucleoside), enalaprilat (a competitive
      inhibitor of angiotensin-converting enzyme), fenoldopam (a D1-dopamine receptor
      agonist), hydralazine, labetalol (an alpha- and beta-adrenergic blocker),
      nicardipine (a calcium channel blocker), nicorandil (K(+)-ATP channel opener),
      nitroglycerin (GTN, a nitrosovasodilator), and sodium nitroprusside (SNP, a
      nitrosovasodilator) were studied in IMA segments pre-contracted with the TxA2
      analogue (U46619, 1.0 x 10(-8) M). Effects of labetalol were also studied in IMA
      segments pre-contracted with norepinephrine (1.0 x 10(-6) M). All drugs were
      added in a cumulative fashion (range 10(-10) to 10(-3) M). RESULTS: All agents in
      the current study, with the exception of enalaprilat, dilated the IMA segments
      pre-contracted with U46619. Only GTN and SNP induced a complete (90-100%)
      relaxation. The order of efficacy of the in vitro relaxation was as follows: SNP,
      GTN, nicardipine, nicorandil, fenoldopam, hydralazine, adenosine, and labetalol.
      The potency was in the order of GTN, SNP, fenoldopam, nicorandil, hydralazine,
      adenosine, and nicardipine. CONCLUSIONS: Various antihypertensive agents are
      effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy
      and potency differ. The in vitro vasodilation may not be simply extrapolated to
      the clinical efficacy or outcome of each antihypertensive therapy; however, our
      data provide additional grounds for the choice of antihypertensive medication.
      Further clinical studies are needed to help to fully elucidate the use of
      different antihypertensive agents and clinical outcomes.

PMID- 15169741
TI  - Effect of prostaglandin E1 on inflammatory responses and gas exchange in patients
      undergoing surgery for oesophageal cancer.
AB  - BACKGROUND: Oesophageal surgery causes morbidity and mortality from respiratory
      complications. We tested the possibility that prostaglandin E1 (PGE1) could
      reduce inflammatory cytokine responses and improve gas exchange after
      oesophagectomy. METHODS: We randomized 14 patients into two groups. One group
      received PGE1 20 ng kg(-1) min(-1) i.v. during anaesthesia (PGE1 group) and the
      other group did not (control group). Anaesthesia was maintained with sevoflurane
      and epidural anaesthesia. During oesophagectomy, ventilation of one lung was
      carried out with a double-lumen bronchial tube. The patients were extubated on or
      after the first postoperative day. Blood samples were taken at induction of
      anaesthesia, at the end of thoracotomy, at the end of the operation, 2 h after
      surgery and on the first day after surgery. RESULTS: The groups were similar for
      ASA physical status, age, FEV1%, operation time, duration of thoracotomy,
      intraoperative fluid volume and blood loss. The arterial blood gas and arterial
      pressure during surgery were also similar in the PGE1 and control groups.
      However, the PaO2/FiO2 ratio on the first day after surgery was significantly
      greater in the PGE1 group compared with the control group. Serum concentrations
      of IL-6 and IL-8 increased after surgery in both groups. IL-6 was significantly
      less in the PGE1 group at the end of the operation and 2 h after the operation.
      CONCLUSIONS: Intraoperative PGE1 reduced IL-6 production in patients undergoing
      oesophagectomy and oxygenation was better in the postoperative period.

PMID- 15169742
TI  - Offending in psychiatric patients after discharge from medium secure units:
      prospective national cohort study.

PMID- 15169743
TI  - General practitioners' perceptions of chronic fatigue syndrome and beliefs about
      its management, compared with irritable bowel syndrome: qualitative study.
AB  - OBJECTIVES: To compare general practitioners' perceptions of chronic fatigue
      syndrome and irritable bowel syndrome and to consider the implications of their
      perceptions for treatment. DESIGN: Qualitative analysis of transcripts of group
      discussions. PARTICIPANTS AND SETTING: A randomly selected sample of 46 general
      practitioners in England. RESULTS: The participants tended to stereotype patients
      with chronic fatigue syndrome as having certain undesirable traits. This
      stereotyping was due to the lack of a precise bodily location; the
      reclassification of the syndrome over time; transgression of social roles, with
      patients seen as failing to conform to the work ethic and "sick role" and
      conflict between doctor and patient over causes and management. These factors led
      to difficulties for many general practitioners in managing patients with chronic
      fatigue syndrome. For both conditions many participants would not consider
      referral for mental health interventions, even though the doctors recognised
      social and psychological factors, because they were not familiar with the
      interventions or thought them unavailable or unnecessary. CONCLUSIONS: Barriers
      to the effective clinical management of patients with irritable bowel syndrome
      and chronic fatigue syndrome are partly due to doctors' beliefs, which result in
      negative stereotyping of patients with chronic fatigue syndrome and the use of
      management strategies for both syndromes that may not take into account the best
      available evidence.

PMID- 15169744
TI  - Rates of caesarean section and instrumental vaginal delivery in nulliparous women
      after low concentration epidural infusions or opioid analgesia: systematic
      review.
AB  - OBJECTIVE: To compare the effects of low concentration epidural infusions of
      bupivacaine with parenteral opioid analgesia on rates of caesarean section and
      instrumental vaginal delivery in nulliparous women. DATA SOURCES: Medline,
      Embase, the Cochrane controlled trials register, and handsearching of the
      International Journal of Obstetric Anesthesia. STUDY SELECTION: Randomised
      controlled trials comparing low concentration epidural infusions with parenteral
      opioids. DATA SYNTHESIS: Seven trials fulfilled the inclusion criteria for meta
      analysis. Epidural analgesia does not seem to be associated with an increased
      risk of caesarean section (odds ratio 1.03, 95% confidence interval 0.71 to 1.48)
      but may be associated with an increased risk of instrumental vaginal delivery
      (2.11, 0.95 to 4.65). Epidural analgesia was associated with a longer second
      stage of labour (weighted mean difference 15.2 minutes, 2.1 to 28.2 minutes).
      More women randomised to receive epidural analgesia had adequate pain relief,
      with fewer changing to parenteral opioids than vice versa (odds ratio 0.1, 0.05
      to 0.22). CONCLUSIONS: Epidural analgesia using low concentration infusions of
      bupivacaine is unlikely to increase the risk of caesarean section but may
      increase the risk of instrumental vaginal delivery. Although women receiving
      epidural analgesia had a longer second stage of labour, they had better pain
      relief.

PMID- 15169745
TI  - Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal
      muscle during prolonged exercise.
AB  - Prolonged moderate-intensity exercise is characterized by a progressive reduction
      in carbohydrate oxidation and concomitant increase in fat oxidation. Pyruvate
      dehydrogenase (PDH) controls the entry of pyruvate into oxidative pathways and is
      a rate-limiting enzyme for carbohydrate metabolism. PDH is controlled by the
      activities of a kinase (PDK, inhibitory) and phosphatase (stimulatory). To test
      the hypothesis that increased PDK activity was associated with decreased PDH
      activity and carbohydrate oxidation during an acute exercise bout, seven
      recreationally active men completed 4 h of cycle exercise at 55% peak oxygen
      consumption. Muscle samples were obtained before and at 10 min and 4 h of
      exercise for the measurement of PDH activity and the extraction of intact
      mitochondria for the measurements of PDK activity and PDK-2 and PDK-4 protein
      expression. Carbohydrate oxidation was reduced (P < 0.05) with exercise duration.
      Muscle glycogen content was lower (P < or = 0.05) at 4 h compared with rest and
      there was no change in muscle pyruvate content from 10 to 240 min during exercise
      (10 min: 0.28 +/- 0.05; 240 min: 0.35 +/- 0.09 mmol/kg dry muscle). PDH activity
      increased (P < 0.05) above resting values at 10 min (2.86 +/- 0.26 mmol.min(
      1).kg wet muscle(-1)), but was lower than 10 min after 4 h (2.23 +/- 0.24
      mmol.min(-1).kg wet muscle(-1)) of exercise. PDK-2 and PDK-4 protein expression
      was not different from rest at 10 min and 4 h of exercise. PDK activity at rest
      averaged 0.081 +/- 0.016 min(-1), was similar at 10 min, and increased (P < 0.05)
      to 0.189 +/- 0.013 min(-1) at 4 h. Although reduced glycolytic flux may have
      played a role in decreasing carbohydrate oxidation, the results suggest that
      increased PDK activity contributed to the reduction in PDH activity and
      carbohydrate oxidation late in prolonged exercise. The increased PDK activity was
      independent of changes in intra-mitochondrial effectors, and PDK-2 and PDK-4
      protein content, suggesting that it was caused by a change in the specific
      activity of the existing kinases.

PMID- 15169746
TI  - Connexin expression and conducted vasodilation along arteriolar endothelium in
      mouse skeletal muscle.
AB  - Functional hyperemia requires the coordination of smooth muscle cell relaxation
      along and between branches of the arteriolar network. Vasodilation is conducted
      from cell to cell along the arteriolar wall through gap junction channels
      composed of connexin protein subunits. Within skeletal muscle, it is unclear
      whether arteriolar endothelium, smooth muscle, or both cell layers provide the
      cellular pathway for conduction. Furthermore, the constitutive profile of
      connexin expression within the microcirculation is unknown. We tested the
      hypothesis that conducted vasodilation and connexin expression are intrinsic to
      the endothelium of arterioles (17 +/- 1 microm diameter) that supply the skeletal
      muscle fibers in the cremaster of anesthetized C57BL/6 mice. ACh delivered to an
      arteriole (500 ms, 1-microA pulse; 1-microm micropipette) produced local dilation
      of 17 +/- 1 microm; conducted vasodilation observed 1 mm upstream was 9 +/- 1
      microm (n = 5). After light-dye treatment to selectively disrupt endothelium (250
      microm segment centered 500 microm upstream, confirmed by loss of local response
      to ACh while constriction to phenylephrine and dilation to sodium nitroprusside
      remained intact), we found that conducted vasodilation was nearly abolished (2 +/
      1 microm; P < 0.05). Whole-mount immunohistochemistry for connexins revealed
      punctate labeling at borders of arteriolar endothelial cells, with connexin40 and
      connexin37 in all branches and connexin43 only in the largest branches.
      Immunoreactivity for connexins was not apparent in smooth muscle or in capillary
      or venular endothelium, despite robust immunolabeling for alpha-actin and
      platelet endothelial cell adhesion molecule-1, respectively. We conclude that
      vasodilation is conducted along the endothelium of mouse skeletal muscle
      arterioles and that connexin40 and connexin37 are the primary connexins forming
      gap junction channels between arteriolar endothelial cells.

PMID- 15169747
TI  - Age-related alterations in NOS and oxidative stress in mesenteric arteries from
      male and female rats.
AB  - Epidemiological evidence suggests that advancing age affects the cardiovascular
      system of men and women differently. The purpose of this study was to determine
      whether the effects of aging on nitric oxide synthase (NOS), oxidative stress,
      and vascular function are different in males and females. Mesenteric arteries
      from young (3 mo) and old (24 mo) male and female Fischer 344/Brown Norway rats
      were studied. Western blot analysis and NOS activity were performed on the
      homogenized mesenteric arterial bed separated into cytosolic and membrane
      associated fractions. Plasma 8-isoprostane measurements assessed oxidative
      stress. Vascular reactivity was determined by using a wire myograph in the
      absence and presence of a NOS inhibitor, N(omega)-nitro-l-arginine, to examine
      endothelial function and basal and stimulated nitric oxide release. In additional
      arteries, reactivity was performed in the presence of polyethylene glycol-SOD to
      assess the impact of superoxide on vascular function. Among females, aging was
      associated with a decline in membrane-associated NOS activity and membrane
      associated NOS III protein expression. Advancing age in males was associated with
      increased cytosolic NOS III protein expression. Among both males and females,
      advancing age resulted in increased oxidative stress. Vascular function was
      maintained with age in arteries from both males and females, and there was no
      difference in either basal or stimulated nitric oxide release with age. Despite
      sex-specific effects of advancing age on the NOS system and increases in markers
      of oxidative stress, vascular function is maintained in mesenteric arteries from
      aged Fischer 344/Brown Norway rats. These data suggest that age-related
      alterations in the resistance vasculature are complex and likely involve multiple
      compensating vasoactive pathways.

PMID- 15169748
TI  - Passive dynamics change leg mechanics for an unexpected surface during human
      hopping.
AB  - Humans running and hopping maintain similar center-of-mass motions, despite large
      changes in surface stiffness and damping. The goal of this study was to determine
      the contributions of anticipation and reaction when human hoppers encounter
      surprise, expected, and random changes from a soft elastic surface (27 kN/m) to a
      hard surface (411 kN/m). Subjects encountered the expected hard surface on every
      fourth hop and the random hard surface on an average of 25% of the hops in a
      trial. When hoppers on a soft surface were surprised by a hard surface, the ankle
      and knee joints were forced into greater flexion by passive interaction with the
      hard surface. Within 52 ms after subjects landed on the surprise hard surface,
      joint flexion increased, and the legs became less stiff than on the soft surface.
      These mechanical changes occurred before electromyography (EMG) first changed 68
      188 ms after landing. Due to the fast mechanical reaction to the surprise hard
      surface, center-of-mass displacement and average leg stiffness were the same as
      on expected and random hard surfaces. This similarity is striking because
      subjects anticipated the expected and random hard surfaces by landing with their
      knees more flexed. Subjects also anticipated the expected hard surface by
      increasing the level of EMG by 24-76% during the 50 ms before landing. These
      results show that passive mechanisms alter leg stiffness for unexpected surface
      changes before muscle EMG changes and may be critical for adjustments to variable
      terrain encountered during locomotion in the natural world.

PMID- 15169749
TI  - Effect of thermal stress on the vestibulosympathetic reflexes in humans.
AB  - Both heat stress and vestibular activation alter autonomic responses; however,
      the interaction of these two sympathetic activators is unknown. To determine the
      effect of heat stress on the vestibulosympathetic reflex, eight subjects
      performed static head-down rotation (HDR) during normothermia and whole body
      heating. Muscle sympathetic nerve activity (MSNA; peroneal microneurography),
      mean arterial blood pressure (MAP), heart rate (HR), and internal temperature
      were measured during the experimental trials. HDR during normothermia caused a
      significant increase in MSNA (Delta5 +/- 1 bursts/min; Delta53 +/- 14 arbitrary
      units/min), whereas no change was observed in MAP, HR, or internal temperature.
      Whole body heating significantly increased internal temperature (Delta0.9 +/- 0.1
      degrees C), MSNA (Delta10 +/- 3 bursts/min; Delta152 +/- 44 arbitrary units/min),
      and HR (Delta25 +/- 6 beats/min), but it did not alter MAP. HDR during whole body
      heating increased MSNA (Delta16 +/- 4 bursts/min; Delta233 +/- 90 arbitrary
      units/min from normothermic baseline), which was not significantly different from
      the algebraic sum of HDR during normothermia and whole body heating (Delta15 +/-
      4 bursts/min; Delta205 +/- 55 arbitrary units/min). These data suggest that heat
      stress does not modify the vestibulosympathetic reflex and that both the
      vestibulosympathetic and thermal reflexes are robust, independent sympathetic
      nervous system activators.

PMID- 15169750
TI  - Candidate mechanical stimuli for hypertrophy during volume overload.
AB  - A myocyte system that senses and responds to mechanical inputs might be activated
      by any number of features of the time-varying length or force signals experienced
      by the myocytes. We therefore characterized left ventricular volume and wall
      stress signals during early volume overload with high spatial and temporal
      resolution. Left ventricular pressure and volume were measured in open-chest
      isoflurane-anesthetized male Sprague-Dawley rats 4 and 7 days after surgical
      creation of an infrarenal arteriovenous fistula or sham operation. Mean wall
      stresses were calculated by using a simple thick-walled ellipsoidal model.
      Consistent with previous reports, this surgical model produced a 66% increase in
      cardiac output and a 10% increase in left ventricular mass by day 7. A number of
      features of the time-varying volume signal (maximum, mean, amplitude, rates of
      rise and fall) were significantly altered during early volume overload, whereas
      many other proposed hypertrophic stimuli, including peak systolic wall stress and
      diastolic strain, were not. Treating hemodynamic variables more generally as time
      varying signals allowed us to identify a wider range of candidate mechanical
      stimuli for hypertrophy (including some not previously proposed in the
      literature) than focusing on standard time points in the cardiac cycle. We
      conclude that features of the time-varying ventricular volume signal and related
      local deformations may drive hypertrophy during volume overload and propose that
      those features of the volume signal that also change during pressure overload
      might be the most interesting candidates for further exploration.

PMID- 15169751
TI  - Sex-specific changes in platelet aggregation and secretion with sexual maturity
      in pigs.
AB  - Cardiovascular disease may begin early in adolescence. Platelets release factors
      contributing to vascular disease. Experiments were designed to test the
      hypothesis that hormonal transitions associated with sexual maturity
      differentially affect platelet aggregation and secretion in males and females.
      Platelets were collected from juvenile (2-3 mo) and sexually mature (adult; 5-6
      mo) male and female pigs (n=8/group). Maturation was evidenced by increased
      weight of reproductive tissue and changes in circulating levels of gonadal
      hormones. Aggregation to ADP (10 microM) and collagen (6 microg/ml) and ATP
      secretion to 50 nM thrombin were determined by turbidimetric analysis and
      bioluminescence, respectively. Total platelet counts, platelet turnover, and mean
      platelet volume did not change with maturity. Platelet aggregation and ATP
      secretion decreased in females but increased in males with maturity, whereas
      total ATP content remained unchanged in platelets from females but increased in
      platelets from males. Platelet fibrinogen receptor, P-selectin expression, and
      receptors for sex steroids did not change with sexual maturation. Plasma C
      reactive protein and brain-type natriuretic peptide also did not change. Results
      indicate that changes in platelet aggregation and secretion change with sexual
      maturity differently in females and males. These observations provide evidence on
      which clinical studies could be designed to examine platelet characteristics in
      human children and young adults.

PMID- 15169752
TI  - Severity of sepsis alters the effects of superoxide anion inhibition in a rat
      sepsis model.
AB  - Previous analysis showed that selective inhibitors of five different host
      inflammatory mediators administered for sepsis, although beneficial with severe
      sepsis and high-control mortality rates, were ineffective or harmful with less
      severe sepsis. We hypothesized that severity of sepsis would also influence
      inhibition of superoxide anion, another inflammatory mediator. To test this, 6-h
      infusions of M40401, a selective SOD mimetic, or placebo were given to antibiotic
      treated rats (n=547) starting 3 h after challenge with differing doses of
      intravenous Escherichia coli designed to produce low- or high-control mortality
      rates. There was a positive and significant (P=0.0008) relationship between the
      efficacy of M40401 on survival rate and control mortality rates. M40401 increased
      or decreased the log (odds ratio of survival) (means +/- SE), dependent on
      whether control mortality rates were greater or less than the median (66%) (+0.19
      +/- 0.12 vs. -0.25 +/- 0.10, P=0.01). In a subset of animals examined (n=152) at
      9 h after E. coli challenge, M40401 increased (mean effect +/- SE compared with
      control) mean arterial blood pressure (8 +/- 5 mmHg) and decreased platelets (-37
      +/- 22 cells x 10(3)/ml) with high-control mortality rates but had opposing
      effects on each parameter (-3 +/- 3 mmHg and 28 +/- 19 cells x 10(3)/ml,
      respectively) with low rates (P < or = 0.05 for the differing effects of M40401
      on each parameter with high- vs. low-control mortality rates). A metaregression
      analysis of published preclinical sepsis studies testing SOD preparations and SOD
      mimetics showed that most (16 of 18) had control mortality rates >66%. However,
      across experiments from published studies, these agents were less beneficial as
      control mortality rate decreased (P=0.03) in a relationship not altered (P=not
      significant) by other variables associated with septic challenge or regimen of
      treatment and which was similar, compared with experiments with M40401 (P=not
      significant). Thus, in these preclinical sepsis models, possibly related to
      divergent effects on vascular function, inhibition of superoxide anion improved
      survival with more severe sepsis and high-control mortality rates but was less
      effective or harmful with less severe sepsis. Extrapolated clinically, inhibition
      of superoxide anion may be most efficacious in septic patients with severe sepsis
      and a high risk of death.

PMID- 15169753
TI  - Noninvasive determination of upper airway resistance and flow limitation.
AB  - We have shown that a polynomial equation, FP = AP3 + BP2 + CP + D, where F is
      flow and P is pressure, can accurately determine the presence of inspiratory flow
      limitation (IFL). This equation requires the invasive measurement of supraglottic
      pressure. We hypothesized that a modification of the equation that substitutes
      time for pressure would be accurate for the detection of IFL and allow for the
      noninvasive measurement of upper airway resistance. The modified equation is Ft =
      At3 + Bt2 + Ct + D, where F is flow and t is time from the onset of inspiration.
      To test our hypotheses, data analysis was performed as follows on 440 randomly
      chosen breaths from 18 subjects. First, we performed linear regression and
      determined that there is a linear relationship between pressure and time in the
      upper airway (R2 0.96 +/- 0.05, slope 0.96 +/- 0.06), indicating that time can be
      a surrogate for pressure. Second, we performed curve fitting and found that
      polynomial equation accurately predicts the relationship between flow and time in
      the upper airway (R2 0.93 +/- 0.12, error fit 0.02 +/- 0.08). Third, we performed
      a sensitivity-specificity analysis comparing the mathematical determination of
      IFL to manual determination using a pressure-flow loop. Mathematical
      determination had both high sensitivity (96%) and specificity (99%). Fourth, we
      calculated the upper airway resistance using the polynomial equation and compared
      the measurement to the manually determined upper airway resistance (also from a
      pressure-flow loop) using Bland-Altman analysis. Mean difference between
      calculated and measured upper airway resistance was 0.0 cmH2O x l(-1) x s(-1)
      (95% confidence interval -0.2, 0.2) with upper and lower limits of agreement of
      2.8 cmH2O x l(-1) x s(-1) and -2.8 cmH2O x l(-1) x s(-1). We conclude that a
      polynomial equation can be used to model the flow-time relationship, allowing for
      the objective and accurate determination of upper airway resistance and the
      presence of IFL.

PMID- 15169754
TI  - Stem cells, plasticity and cancer - uncomfortable bed fellows.
AB  - Stem cell research is a vibrant and rapidly moving field of science that
      investigates self-renewing cells in the adult and embryo. Two debates currently
      exist in the stem cell field concerning the transcriptional redirection of stem
      cell differentiation and fate, and the reorganization of cell commitment through
      nuclear reprogramming caused by cell fusion and nuclear transfer. The recent
      Keystone Symposium in Colorado on stem cells, organised by Fiona Watt and Leonard
      Zon, brought together both leading and upcoming researchers in the field to
      explore stem cell biology and these issues.

PMID- 15169755
TI  - The maize duplicate genes narrow sheath1 and narrow sheath2 encode a conserved
      homeobox gene function in a lateral domain of shoot apical meristems.
AB  - The narrow sheath (ns) phenotype of maize is a duplicate factor trait conferred
      by mutations at the unlinked loci ns1 and ns2. Recessive mutations at each locus
      together confer the phenotypic deletion of a lateral compartment in maize leaves
      and leaf homologs. Previous analyses revealed that the mediolateral axis of maize
      leaves is comprised of at least two distinct compartments, and suggest a model
      whereby NS function is required to recruit leaf founder cells from a lateral
      compartment of maize meristems. Genomic clones of two maize homeodomain-encoding
      genes were isolated by homology to the WUSCHEL-related gene PRESSED FLOWER (PRS).
      PRS is required for lateral sepal development in Arabidopsis, although no leaf
      phenotype is reported. Co-segregation of the ns phenotype with multiple mutant
      alleles of two maize PRS homologs confirms their allelism to ns1 and ns2.
      Analyses of NS protein accumulation verify that the ns-R mutations are null
      alleles. ns transcripts are detected in two lateral foci within maize meristems,
      and in the margins of lateral organ primordia. Whereas ns1 and ns2 transcripts
      accumulate to equivalent levels in shoot meristems of vegetative seedlings, ns2
      transcripts predominate in female inflorescences. Previously undiscovered
      phenotypes in the pressed flower mutant support a model whereby the morphology of
      eudicot leaves and monocot grass leaves has evolved via the differential
      elaboration of upper versus lower leaf zones. A model implicating an
      evolutionarily conserved NS/PRS function during recruitment of organ founder
      cells from a lateral domain of plant meristems is discussed.

PMID- 15169756
TI  - Nemo is an inducible antagonist of Wingless signaling during Drosophila wing
      development.
AB  - The cellular events that govern patterning during animal development must be
      precisely regulated. This is achieved by extrinsic factors and through the action
      of both positive and negative feedback loops. Wnt/Wg signals are crucial across
      species in many developmental patterning events. We report that Drosophila nemo
      (nmo) acts as an intracellular feedback inhibitor of Wingless (Wg) and that it is
      a novel Wg target gene. Nemo antagonizes the activity of the Wg signal, as
      evidenced by the finding that reduction of nmo rescues the phenotypic defects
      induced by misexpression of various Wg pathway components. In addition, the
      activation of Wg-dependent gene expression is suppressed in wing discs
      ectopically expressing nmo and enhanced cell autonomously in nmo mutant clones.
      We find that nmo itself is a target of Wg signaling in the imaginal wing disc.
      nmo expression is induced upon high levels of Wg signaling and can be inhibited
      by interfering with Wg signaling. Finally, we observe alterations in Arm
      stabilization upon modulation of Nemo. These observations suggest that the
      patterning mechanism governed by Wg involves a negative feedback circuit in which
      Wg induces expression of its own antagonist Nemo.

PMID- 15169757
TI  - Gene expression during early ascidian metamorphosis requires signalling by Hemps,
      an EGF-like protein.
AB  - Hemps, a novel epidermal growth factor (EGF)-like protein, is expressed during
      larval development and early metamorphosis in the ascidian Herdmania curvata and
      plays a direct role in triggering metamorphosis. In order to identify downstream
      genes in the Hemps pathway we used a gene expression profiling approach, in which
      we compared post-larvae undergoing normal metamorphosis with larval metamorphosis
      blocked with an anti-Hemps antibody. Molecular profiling revealed that there are
      dynamic changes in gene expression within the first 30 minutes of normal
      metamorphosis with a significant portion of the genome (approximately 49%) being
      activated or repressed. A more detailed analysis of the expression of 15 of these
      differentially expressed genes through embryogenesis, larval development and
      metamorphosis revealed that while there is a diversity of temporal expression
      patterns, a number of genes are transiently expressed during larval development
      and metamorphosis. These and other differentially expressed genes were localised
      to a range of specific cell and tissue types in Herdmania larvae and post-larvae.
      The expression of approximately 24% of the genes that were differentially
      expressed during early metamorphosis was affected in larvae treated with the anti
      Hemps antibody. Knockdown of Hemps activity affected the expression of a range of
      genes within 30 minutes of induction, suggesting that the Hemps pathway directly
      regulates early response genes at metamorphosis. In most cases, it appears that
      the Hemps pathway contributes to the modulation of gene expression, rather than
      initial gene activation or repression. A total of 151 genes that displayed the
      greatest alterations in expression in response to anti-Hemps antibody were
      sequenced. These genes were implicated in a range of developmental and
      physiological roles, including innate immunity, signal transduction and in the
      regulation of gene transcription. These results suggest that there is significant
      gene activity during the very early stages of H. curvata metamorphosis and that
      the Hemps pathway plays a key role in regulating the expression of many of these
      genes.

PMID- 15169758
TI  - her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch
      signalling.
AB  - her3 encodes a zebrafish bHLH protein of the Hairy-E(Spl) family. During
      embryogenesis, the gene is transcribed exclusively in the developing central
      nervous system, according to a fairly simple pattern that includes territories in
      the mesencephalon/rhombencephalon and the spinal cord. In all territories, the
      her3 transcription domain encompasses regions in which neurogenin 1 (neurog1) is
      not transcribed, suggesting regulatory interactions between the two genes.
      Indeed, injection of her3 mRNA leads to repression of neurog1 and to a reduction
      in the number of primary neurones, whereas her3 morpholino oligonucleotides cause
      ectopic expression of neurog1 in the rhombencephalon. Fusions of Her3 to the
      transactivation domain of VP16 and to the repression domain of Engrailed show
      that Her3 is indeed a transcriptional repressor. Dissection of the Her3 protein
      reveals two possible mechanisms for transcriptional repression: one mediated by
      the bHLH domain and the C-terminal WRPW tetrapeptide; and the other involving the
      N-terminal domain and the orange domain. Gel retardation assays suggest that the
      repression of neurog1 transcription occurs by binding of Her3 to specific DNA
      sequences in the neurog1 promoter. We have examined interrelationships of her3
      with members of the Notch signalling pathway by the Gal4-UAS technique and mRNA
      injections. The results indicate that Her3 represses neurog1 and, probably as a
      consequence of the neurog1 repression, deltaA, deltaD and her4. Moreover, Her3
      represses its own transcription as well. Surprisingly, and in sharp contrast to
      other members of the E(spl) gene family, transcription of her3 is repressed
      rather than activated by Notch signalling.

PMID- 15169760
TI  - Asymmetric leaf development and blade expansion in Arabidopsis are mediated by
      KANADI and YABBY activities.
AB  - Asymmetric development of plant lateral organs is initiated by a partitioning of
      organ primordia into distinct domains along their adaxial/abaxial axis. Two
      primary determinants of abaxial cell fate are members of the KANADI and YABBY
      gene families. Progressive loss of KANADI activity in loss-of-function mutants
      results in progressive transformation of abaxial cell types into adaxial ones and
      a correlated loss of lamina formation. Novel, localized planes of blade expansion
      occur in some kanadi loss-of-function genotypes and these ectopic lamina
      outgrowths are YABBY dependent. We propose that the initial asymmetric leaf
      development is regulated primarily by mutual antagonism between KANADI and PHB
      like genes, which is translated into polar YABBY expression. Subsequently, polar
      YABBY expression contributes both to abaxial cell fate and to abaxial/adaxial
      juxtaposition-mediated lamina expansion.

PMID- 15169759
TI  - Histone deacetylase 1 is required to repress Notch target gene expression during
      zebrafish neurogenesis and to maintain the production of motoneurones in response
      to hedgehog signalling.
AB  - Histone deacetylases (Hdacs) are widely implicated as key components of
      transcriptional silencing mechanisms. Here, I show that hdac1 is specifically
      required in the zebrafish embryonic CNS to maintain neurogenesis. In hdac1 mutant
      embryos, the Notch-responsive E(spl)-related neurogenic gene her6 is ectopically
      expressed at distinct sites within the developing CNS and proneural gene
      expression is correspondingly reduced or eliminated. Using an hdac1-specific
      morpholino, I show that this requirement for hdac1 is epistatic to the
      requirement for Notch signalling. Consequently, hdac1-deficient embryos exhibit
      several defects of neuronal specification and patterning, including a dramatic
      deficit of hedgehog-dependent branchiomotor neurones that is refractory to
      elevated levels of hedgehog signalling. Thus, in the zebrafish embryo, hdac1 is
      an essential component of the transcriptional silencing machinery that supports
      the formation and subsequent differentiation of neuronal precursors.

PMID- 15169761
TI  - Rescue of enzyme deficiency in embryonic diaphragm in a mouse model of metabolic
      myopathy: Pompe disease.
AB  - Several human genetic diseases that affect striated muscle have been modeled by
      creating knockout mouse strains. However, many of these are perinatal lethal
      mutations that result in death from respiratory distress within hours after
      birth. As the diaphragm muscle does not contract until birth, the sudden increase
      in diaphragm activity creates permanent injury to the muscle causing it to fail
      to meet respiratory demands. Therefore, the impact of these mutations remains
      hidden throughout embryonic development and early death prevents investigators
      from performing detailed studies of other striated muscle groups past the
      neonatal stage. Glycogen storage disease type II (GSDII), caused by a deficiency
      in acid alpha-glucosidase (GAA), leads to lysosomal accumulation of glycogen in
      all cell types and abnormal myofibrillogenesis in striated muscle. Contractile
      function of the diaphragm muscle is severely affected in both infantile-onset and
      late-onset individuals, with death often resulting from respiratory failure. The
      knockout mouse model of GSDII survives well into adulthood despite the gradual
      weakening of all striated muscle groups. Using this model, we investigated the
      delivery of recombinant adeno-associated virus (rAAV) vectors encoding the human
      GAA cDNA to the developing embryo. Results indicate specific high-level
      transduction of diaphragm tissue, leading to activity levels up to 10-fold higher
      than normal and restoration of normal contractile function. Up to an estimated 50
      vector copies per diploid genome were quantified in treated diaphragms.
      Histological glycogen staining of treated diaphragms revealed prevention of
      lysosomal glycogen accumulation in almost all fibers when compared with untreated
      controls. This method could be employed with disease models where specific rescue
      of the diaphragm would allow for increased survival and thus further
      investigation into the impact of the gene deletion on other striated muscle
      groups.

PMID- 15169762
TI  - The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates
      Pak.
AB  - The Down syndrome cell adhesion molecule (DSCAM) is a member of the
      immunoglobulin superfamily that maps to a Down syndrome region of chromosome
      21q22.2-22.3. In Drosophila, Dscam functions as an axon guidance receptor
      regulating targeting and branching. Genetic and biochemical studies have shown
      that in Drosophila, Dscam activates Pak1 via the Dock adaptor molecule. The
      extracellular domain of human DSCAM is highly homologous to the Drosophila
      protein; however, the intracellular domains of both human and Drosophila DSCAM
      share no obvious sequence identity. To study the signaling mechanisms of human
      DSCAM, we investigated the interaction between DSCAM and potential downstream
      molecules. We found that DSCAM directly binds to Pak1 and stimulates Pak1
      phosphorylation and activity, unlike Drosophila where an adaptor protein Dock
      mediates the interaction between Dscam and Pak1. We also observed that DSCAM
      activates both JNK and p38 MAP kinases. Furthermore, expression of the
      cytoplasmic domain of DSCAM induces a morphological change in cultured cells that
      is JNK-dependent. These observations suggest that human DSCAM also signals
      through Pak1 and may function in axon guidance similar to the Drosophila Dscam.

PMID- 15169763
TI  - Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate
      RNA binding, protein-protein interactions, and subcellular localization.
AB  - Cleavage factor I(m) (CF I(m)) is required for the first step in pre-mRNA 3'-end
      processing and can be reconstituted in vitro from its heterologously expressed 25
      and 68-kDa subunits. The binding of CF I(m) to the pre-mRNA is one of the
      earliest steps in the assembly of the cleavage and polyadenylation machinery and
      facilitates the recruitment of other processing factors. We identified regions in
      the subunits of CF I(m) involved in RNA binding, protein-protein interactions,
      and subcellular localization. CF I(m)68 has a modular domain organization
      consisting of an N-terminal RNA recognition motif and a C-terminal alternating
      charge domain. However, the RNA recognition motif of CF I(m)68 on its own is not
      sufficient to bind RNA but is necessary for association with the 25-kDa subunit.
      RNA binding appears to require a CF I(m)68/25 heterodimer. Whereas multiple
      protein interactions with other 3'-end-processing factors are detected with CF
      I(m)25, CF I(m)68 interacts with SRp20, 9G8, and hTra2beta, members of the SR
      family of splicing factors, via its C-terminal alternating charge domain. This
      domain is also required for targeting CF I(m)68 to the nucleus. However, CF
      I(m)68 does not concentrate in splicing speckles but in foci that partially
      colocalize with paraspeckles, a subnuclear component in which other proteins
      involved in transcriptional control and RNA processing have been found.

PMID- 15169764
TI  - Hypoxia-induced synthesis of hemoglobin in the crustacean Daphnia magna is
      hypoxia-inducible factor-dependent.
AB  - Of the four known globin genes that exist in the fresh-water crustacean Daphnia
      magna, several are individually induced by hypoxia, lending pale normoxic animals
      a visible red color when challenged by oxygen deprivation. The promoter regions
      of the Daphnia globin genes each contain numerous hypoxia response elements
      (HREs) as potential binding sites for hypoxia-inducible factors (HIFs). Daphnia
      HIF, bound to human HRE sequences, was detected in extracts from hypoxic (red),
      but not normoxic (pale), animals. Taking advantage of the phylogenetically
      conserved HIF/HRE recognition, we employed heterologous transfections of HIF
      expressing human and Drosophila cells to model HIF signaling in Daphnia. These
      experiments revealed that three functional HREs within the promoter of the D.
      magna globin-2 gene cooperate for maximal hypoxic induction of a downstream
      luciferase reporter gene. Two of these three cis-elements, at promoter positions 
      258 and -107, are able to specifically bind human, Drosophila, or Daphnia HIF
      complexes in vitro. The same two sites are also necessary for maximal induction
      of reporter transcription under low oxygen tension in the presence of either
      endogenous human or overexpressed Drosophila HIF proteins. The third motif of the
      globin-2 gene promoter, a CACGTG palindrome at position -146, functions as a
      docking site for an unknown constitutive transcription factor. In human cells,
      this -146 complex interferes with HIF occupancy at the adjacent -107 HRE and thus
      controls the extent of HIF-mediated hypoxic activation of the downstream target.

PMID- 15169765
TI  - Regulation of Drosophila hypoxia-inducible factor (HIF) activity in SL2 cells:
      identification of a hypoxia-induced variant isoform of the HIFalpha homolog gene
      similar.
AB  - Although hypoxia-inducible factor-alpha (HIFalpha) subunit-specific hydroxylation
      and proteolytic breakdown explain the binary switch between the presence
      (hypoxia) and absence (normoxia) of HIFs, little is known of the mechanisms that
      fine-tune HIF activity under constant, rather than changing, oxygen tensions.
      Here, we report that the Drosophila HIFalpha homolog, the basic helix-loop
      helix/PAS protein Sima (Similar), in hypoxic cultures of SL2 cells is expressed
      in full-length (fl) and splice variant (sv) isoforms. The following evidence
      supports the role of flSima as functional HIFalpha and the role of SL2 HIF as a
      transcriptional activator or suppressor. The pO(2) dependence of Sima abundance
      matched that of HIF activity. HIF-dependent changes in candidate target gene
      expression were detected through variously effective stimuli: hypoxia (strong) >
      iron chelation, e.g. desferrioxamine (moderate) >> transition metals, e.g. cobalt
      approximately normoxia (ineffective). Sima overexpression augmented hypoxic
      induction or suppression of different targets. In addition to the full-length
      exon 1-12 transcript yielding the 1510-amino acid HIFalpha homolog, the sima gene
      also expressed, specifically under hypoxia, an exon 1-7/12 splice variant, which
      translated into a 426-amino acid Sima truncation termed svSima. svSima contains
      basic helix-loop-helix and PAS sequences identical to those of flSima, but,
      because of deletion of exons 8-11, lacks the oxygen-dependent degradation domain
      and nuclear localization signals. Overexpressed svSima failed to transactivate
      reporter genes. However, it attenuated HIF (Sima.Tango)-stimulated reporter
      expression in a dose-dependent manner. Thus, svSima has the potential to regulate
      Drosophila HIF function under steady and hypoxic pO(2) by creating a cytosolic
      sink for the Sima partner protein Tango.

PMID- 15169768
TI  - MUC1 initiates a calcium signal after ligation by intercellular adhesion molecule
      1.
AB  - The MUC1 mucin is normally restricted to the apical surface of breast epithelial
      cells. In tumors, it is frequently overexpressed and underglycosylated. The MUC1
      peptide core mediates firm adhesion of tumor cells to adjacent cells via binding
      to intercellular adhesion molecule-1 (ICAM-1). There is increasing evidence that
      MUC1 is involved in signaling, with current reports focusing on phosphorylation
      of the MUC1 cytoplasmic tail after indirect or artificial modes of stimulation.
      ICAM-1 is the only known direct ligand of the MUC1 extracellular domain. The data
      presented herein show that MUC1 expressed on the surface of breast cancer cell
      lines or transfected 293T cells can initiate a calcium-based oscillatory signal
      on contact with ICAM-1-transfected NIH 3T3 cells, and we present a novel method
      of quantifying and comparing calcium oscillations. The MUC1-induced signal
      appears to be distinct from those previously described, and may involve a Src
      family kinase, phosphoinositol 3-kinase, phospholipase C, and lipid rafts, but
      not mitogen-activated protein kinase. As calcium signaling has been associated
      with cytoskeletal change and motility, it is possible that the functions of MUC1
      include heterotypic cell-cell adhesion followed by a calcium-based promigratory
      signal within tumor cells, thus facilitating metastasis.

PMID- 15169766
TI  - Absence of cardiolipin results in temperature sensitivity, respiratory defects,
      and mitochondrial DNA instability independent of pet56.
AB  - Cardiolipin (CL) is a dimeric phospholipid localized primarily in the
      mitochondrial membrane. Previous studies have shown that yeast cells containing a
      disruption of CRD1, the structural gene encoding CL synthase, exhibit temperature
      sensitive colony formation and multiple mitochondrial defects. A recent report
      (Zhang, M., Su, X., Mileykovskaya, E., Amoscato, A. A., and Dowhan, W. (2003) J.
      Biol. Chem. 278, 35204-35210) suggested that defects associated with CL
      deficiency may result from the reduced expression of PET56 in crd1 Delta mutant
      backgrounds and should be reevaluated. In the current study, we present evidence
      that CL deficiency leads to mitochondrial DNA instability, loss of viability, and
      defects in oxidative phosphorylation at elevated temperatures. The observed
      mutant phenotypes are characteristic of crd1 Delta mutant cells of both PET56 and
      pet56 backgrounds and are complemented by an episomal copy of CRD1 but not by
      expression of the PET56 gene. Phosphatidylglycerol is elevated in crd1 Delta
      mutant cells when grown in the presence of fermentable and non-fermentable carbon
      sources, although the extent of the increase is higher in nonfermentable medium.
      An increase in the ratio of phosphatidylethanolamine to phosphatidylcholine was
      also apparent in the mutant. These findings demonstrate that CRD1, independent of
      PET56, is required for optimal mitochondrial function and for an essential
      cellular function at elevated temperatures.

PMID- 15169767
TI  - The binding specificity of OppA determines the selectivity of the oligopeptide
      ATP-binding cassette transporter.
AB  - The purification and functional reconstitution of a five-component oligopeptide
      ATP-binding cassette transporter with a remarkably wide substrate specificity are
      described. High-affinity peptide uptake was dependent on liganded substrate
      binding protein OppA, which interacts with the translocator OppBCDF with higher
      affinity than unliganded OppA. Transport screening with combinatorial peptide
      libraries revealed that (i) the Opp transporter is not selective with respect to
      amino acid side chains of the transported peptides; (ii) any peptide that can
      bind to OppA is transported via Opp, including very long peptides up to 35
      residues long; and (iii) the binding specificity of OppA largely determines the
      overall transport selectivity.

PMID- 15169769
TI  - Single unpaired nucleotides facilitate HIV-1 reverse transcriptase displacement
      synthesis through duplex RNA.
AB  - During reverse transcription of viral RNA, HIV-1 reverse transcriptase (RT)
      encounters RNA stem-loop structures that require displacement synthesis activity
      in which RT disrupts the RNA helix to access the template strand. A primer
      extension assay was developed to assess HIV-1 RT RNA displacement synthesis
      activity in vitro. Initial results revealed that HIV-1 RT performs only limited
      amounts of RNA displacement through long stretches of RNA duplex, with the
      majority of synthesis stalling at sequence-dependent pause positions. DNA
      displacement synthesis through the same sequence, however, proceeded rapidly to
      the end of the template. The RNA folding algorithm mfold indicated that the
      presence of an unpaired nucleotide, or "bulge," along the RNA duplex would
      promote helix melting ahead of the DNA primer terminus to create a small gap of
      nondisplacement synthesis. Primer extension assays using substrates possessing
      single-nucleotide bulges in the nontemplate strand near pause sites resulted in
      diminished pausing at positions within the predicted melted region. Surprisingly,
      the bulges also reduced pausing distal to the bulge at positions that are
      expected to remain base-paired. Further analysis revealed that stalling during
      RNA displacement synthesis results from the displaced RNA re-annealing to the
      template strand thus forcing the primer terminus to become unpaired and,
      therefore, not extendable. Introduction of a bulge facilitates displacement
      synthesis through distal regions by increasing RT processivity in the vicinity of
      a bulge and reducing the impact of branch migration on primer extension.

PMID- 15169770
TI  - Engineered RNase P ribozymes increase their cleavage activities and efficacies in
      inhibiting viral gene expression in cells by enhancing the rate of cleavage and
      binding of the target mRNA.
AB  - Engineered RNase P ribozymes are promising gene-targeting agents that can be used
      in both basic research and clinical applications. We have previously selected
      ribozyme variants for their activity in cleaving an mRNA substrate from a pool of
      ribozymes containing randomized sequences. In this study, one of the variants was
      used to target the mRNA encoding thymidine kinase (TK) of herpes simplex virus 1
      (HSV-1). The variant exhibited enhanced cleavage and substrate binding and was at
      least 30 times more efficient in cleaving TK mRNA in vitro than the ribozyme
      derived from the wild type sequence. Our results provide the first direct
      evidence to suggest that a point mutation at nucleotide 95 of RNase P catalytic
      RNA from Escherichia coli (G(95) --> U(95)) increases the rate of cleavage,
      whereas another mutation at nucleotide 200 (A(200) --> C(200)) enhances substrate
      binding of the ribozyme. A reduction of about 99% in TK expression was observed
      in cells expressing the variant, whereas a 70% reduction was found in cells
      expressing the ribozyme derived from the wild type sequence. Thus, the RNase P
      ribozyme variant is highly effective in inhibiting HSV-1 gene expression. Our
      study demonstrates that ribozyme variants increase their cleavage activity and
      efficacy in blocking gene expression in cells through enhanced substrate binding
      and rate of cleavage. These results also provide insights into the mechanism of
      how RNase P ribozymes efficiently cleave an mRNA substrate and, furthermore,
      facilitate the development of highly active RNase P ribozymes for gene-targeting
      applications.

PMID- 15169771
TI  - Escherichia coli nucleoside diphosphate kinase interactions with T4 phage
      proteins of deoxyribonucleotide synthesis and possible regulatory functions.
AB  - In both prokaryotic and eukaryotic organisms, nucleoside diphosphate kinase is a
      multifunctional protein, with well defined functions in ribo- and
      deoxyribonucleoside triphosphate biosynthesis and more recently described
      functions in genetic and metabolic regulation, signal transduction, and DNA
      repair. This paper concerns two unusual properties of nucleoside diphosphate
      (NDP) kinase from Escherichia coli: 1) its ability to interact specifically with
      enzymes encoded by the virulent bacteriophage T4 and 2) its roles in regulating
      metabolism of the host cell. By means of optical biosensor analysis, fluorescence
      spectroscopy, immunoprecipitation, and glutathione S-transferase pull-down
      assays, we have shown that E. coli NDP kinase interacts directly with T4
      thymidylate synthase, aerobic ribonucleotide reductase, dCTPase-dUTPase, gene 32
      single-strand DNA-binding protein, and deoxycytidylate hydroxymethylase. The
      interactions with ribonucleotide reductase and with gp32 are enhanced by
      nucleoside triphosphates, suggesting that the integrity of the T4 dNTP synthetase
      complex in vivo is influenced by the composition of the nucleotide pool. The
      other investigations in this work stem from the unexpected finding that E. coli
      NDP kinase is dispensable for successful T4 phage infection, and they deal with
      two observations suggesting that the NDP kinase protein plays a genetic role in
      regulating metabolism of the host cell: 1) the elevation of CTP synthetase
      activity in an ndk mutant, in which the structural gene for NDP kinase is
      disrupted, and 2) the apparent ability of NDP kinase to suppress anaerobic growth
      in a pyruvate kinase-negative E. coli mutant. Our data indicate that the
      regulatory roles are metabolic, not genetic, in nature.

PMID- 15169772
TI  - Identification of a major inter-ring coupling step in the GroEL reaction cycle.
AB  - It has been shown previously that the double-ring structure of GroEL can be
      converted to a single-ring species by site-directed amino acid replacements at
      the ring interface and that the resultant molecule retains many of the crucial
      chaperonin properties; it is structurally stable, hydrolytically active, and can
      bind both the co-chaperonin, GroES, and unfolded substrate proteins. By comparing
      the behavior of the double- and single-ring structures in response to nucleotide
      binding and hydrolysis, we elucidate steps in the ATP-driven reaction cycle at
      which there is conformational coupling between the rings. Remarkably, the parting
      of the rings has little effect either on the thermodynamic properties of ATP
      binding or on the ATP-induced conformational changes prior to hydrolysis.
      However, there is a marked effect on the rate-limiting process in the steady
      state cycle; a step that is coincident with bond cleavage in ATP. The effect of
      the ring-ring interaction is to increase its activation enthalpy from 42.0 to
      94.2 kJ/mol. These results show that the major conformational coupling step,
      where structural rearrangements in one ring are propagated to the other, is the
      slowest process the ATPase cycle of GroEL.

PMID- 15169773
TI  - Laboratory-evolved vanillyl-alcohol oxidase produces natural vanillin.
AB  - The flavoenzyme vanillyl-alcohol oxidase was subjected to random mutagenesis to
      generate mutants with enhanced reactivity to creosol (2-methoxy-4-methylphenol).
      The vanillyl-alcohol oxidase-mediated conversion of creosol proceeds via a two
      step process in which the initially formed vanillyl alcohol (4-hydroxy-3
      methoxybenzyl alcohol) is oxidized to the widely used flavor compound vanillin (4
      hydroxy-3-methoxybenzaldehyde). The first step of this reaction is extremely slow
      due to the formation of a covalent FAD N-5-creosol adduct. After a single round
      of error-prone PCR, seven mutants were generated with increased reactivity to
      creosol. The single-point mutants I238T, F454Y, E502G, and T505S showed an up to
      40-fold increase in catalytic efficiency (kcat/Km) with creosol compared with the
      wild-type enzyme. This enhanced reactivity was due to a lower stability of the
      covalent flavin-substrate adduct, thereby promoting vanillin formation. The
      catalytic efficiencies of the mutants were also enhanced for other ortho
      substituted 4-methylphenols, but not for p-cresol (4-methylphenol). The replaced
      amino acid residues are not located within a distance of direct interaction with
      the substrate, and the determined three-dimensional structures of the mutant
      enzymes are highly similar to that of the wild-type enzyme. These results clearly
      show the importance of remote residues, not readily predicted by rational design,
      for the substrate specificity of enzymes.

PMID- 15169774
TI  - How oligomerization contributes to the thermostability of an archaeon protein.
      Protein L-isoaspartyl-O-methyltransferase from Sulfolobus tokodaii.
AB  - To study how oligomerization may contribute to the thermostability of archaeon
      proteins, we focused on a hexameric protein, protein L-isoaspartyl-O
      methyltransferase from Sulfolobus tokodaii (StoPIMT). The crystal structure shows
      that StoPIMT has a distinctive hexameric structure composed of monomers
      consisting of two domains: an S-adenosylmethionine-dependent methyltransferase
      fold domain and a C-terminal alpha-helical domain. The hexameric structure
      includes three interfacial contact regions: major, minor, and coiled-coil.
      Several C-terminal deletion mutants were constructed and characterized. The
      hexameric structure and thermostability were retained when the C-terminal alpha
      helical domain (Tyr(206)-Thr(231)) was deleted, suggesting that oligomerization
      via coiled-coil association using the C-terminal alpha-helical domains did not
      contribute critically to hexamerization or to the increased thermostability of
      the protein. Deletion of three additional residues located in the major contact
      region, Tyr(203)-Asp(204)-Asp(205), led to a significant decrease in hexamer
      stability and chemico/thermostability. Although replacement of Thr(146) and
      Asp(204), which form two hydrogen bonds in the interface in the major contact
      region, with Ala did not affect hexamer formation, these mutations led to a
      significant decrease in thermostability, suggesting that two residues in the
      major contact region make significant contributions to the increase in stability
      of the protein via hexamerization. These results suggest that cooperative
      hexamerization occurs via interactions of "hot spot" residues and that a couple
      of interfacial hot spot residues are responsible for enhancing thermostability
      via oligomerization.

PMID- 15169775
TI  - Early steps on the DNA ladder--a recollection.

PMID- 15169776
TI  - Transactivator of transcription fusion protein transduction causes membrane
      inversion.
AB  - The transactivator of transcription (TAT) protein transduction domain is an 11
      amino acid positively charged peptide that has been shown to pull diverse
      molecules across cell membranes in vitro and in vivo. Fusion proteins constructed
      with TAT rapidly enter and exit cells and have been shown to cross intracellular
      membranes as well. Electrostatic interactions between TAT and the cell membrane
      have been implicated as a part of the mechanism of transduction. Here, we report
      that TAT transduction causes membrane phospholipid rearrangement as evidenced by
      detection of phosphatidylserine on the outer surface of the cell membrane.
      Furthermore, these rearrangements can be blocked by positively charged
      polylysine, further implicating electrostatic interactions as a part of the
      mechanism. Neither apoptosis nor necrosis is induced in these cells after
      exposure to TAT. We conclude that the process of TAT.GFP transduction causes
      phosphatidylserine to translocate from the inner to the outer leaflet of the
      plasma membrane. These results provide insight into the mechanism of TAT protein
      transduction domain transduction.

PMID- 15169777
TI  - A novel fermentation/respiration switch protein regulated by enzyme IIAGlc in
      Escherichia coli.
AB  - The bacterial phosphoenolpyruvate:sugar phosphotransferase system regulates a
      variety of physiological processes as well as effecting sugar transport. The crr
      gene product (enzyme IIA(Glc) (IIA(Glc))) mediates some of these regulatory
      phenomena. In this report, we characterize a novel IIA(Glc)-binding protein from
      Escherichia coli extracts, discovered using ligand-fishing with surface plasmon
      resonance spectroscopy. This protein, which we named FrsA
      (fermentation/respiration switch protein), is the 47-kDa product of the yafA
      gene, previously denoted as "function unknown." FrsA forms a 1:1 complex
      specifically with the unphosphorylated form of IIA(Glc), with the highest
      affinity of any protein thus far shown to interact with IIA(Glc). Orthologs of
      FrsA have been found to exist only in facultative anaerobes belonging to the
      gamma-proteobacterial group. Disruption of frsA increased cellular respiration on
      several sugars including glucose, while increased FrsA expression resulted in an
      increased fermentation rate on these sugars with the concomitant accumulation of
      mixed-acid fermentation products. These results suggest that IIA(Glc) regulates
      the flux between respiration and fermentation pathways by sensing the available
      sugar species via a phosphorylation state-dependent interaction with FrsA.

PMID- 15169778
TI  - Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase
      B/Akt-dependent phosphorylation.
AB  - The tumor suppressor p53 is commonly inhibited under conditions in which the
      phosphatidylinositide 3'-OH kinase/protein kinase B (PKB)Akt pathway is
      activated. Intracellular levels of p53 are controlled by the E3 ubiquitin ligase
      Mdm2. Here we show that PKB inhibits Mdm2 self-ubiquitination via phosphorylation
      of Mdm2 on Ser(166) and Ser(188). Stimulation of human embryonic kidney 293 cells
      with insulin-like growth factor-1 increased Mdm2 phosphorylation on Ser(166) and
      Ser(188) in a phosphatidylinositide 3'-OH kinase-dependent manner, and the
      treatment of both human embryonic kidney 293 and COS-1 cells with
      phosphatidylinositide 3'-OH kinase inhibitor LY-294002 led to proteasome-mediated
      Mdm2 degradation. Introduction of a constitutively active form of PKB together
      with Mdm2 into cells induced phosphorylation of Mdm2 at Ser(166) and Ser(188) and
      stabilized Mdm2 protein. Moreover, mouse embryonic fibroblasts lacking PKBalpha
      displayed reduced Mdm2 protein levels with a concomitant increase of p53 and
      p21(Cip1), resulting in strongly elevated apoptosis after UV irradiation. In
      addition, activation of PKB correlated with Mdm2 phosphorylation and stability in
      a variety of human tumor cells. These findings suggest that PKB plays a critical
      role in controlling of the Mdm2.p53 signaling pathway by regulating Mdm2
      stability.

PMID- 15169779
TI  - The N-terminal carbohydrate recognition site of the cation-independent mannose 6
      phosphate receptor.
AB  - The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays a
      critical role in the trafficking of newly synthesized mannose 6-phosphate
      containing acid hydrolases to the lysosome. The receptor contains two high
      affinity carbohydrate recognition sites within its 15-domain extracytoplasmic
      region, with essential residues for carbohydrate recognition located in domain 3
      and domain 9. Previous studies have shown that these two sites are distinct with
      respect to carbohydrate specificity. In addition, expression of truncated forms
      of the CI-MPR demonstrated that domain 9 can be expressed as an isolated domain,
      retaining high affinity (Kd approximately 1 nm) carbohydrate binding, whereas
      expression of domain 3 alone resulted in a protein capable of only low affinity
      binding (Kd approximately 1 microm) toward a lysosomal enzyme. In the current
      report the crystal structure of the N-terminal 432 residues of the CI-MPR,
      encompassing domains 1-3, was solved in the presence of bound mannose 6
      phosphate. The structure reveals the unique architecture of this carbohydrate
      binding pocket and provides insight into the ability of this site to recognize a
      variety of mannose-containing sugars.

PMID- 15169780
TI  - Investigation of the cyclobutane pyrimidine dimer (CPD) photolyase DNA
      recognition mechanism by NMR analyses.
AB  - The cyclobutane pyrimidine dimer (CPD) is one of the major forms of DNA damage
      caused by irradiation with ultraviolet (UV) light. CPD photolyases recognize and
      repair UV-damaged DNA. The DNA recognition mechanism of the CPD photolyase has
      remained obscure because of a lack of structural information about DNA-CPD
      photolyase complexes. In order to elucidate the CPD photolyase DNA binding mode,
      we performed NMR analyses of the DNA-CPD photolyase complex. Based upon results
      from (31)P NMR measurements, in combination with site-directed mutagenesis, we
      have demonstrated the orientation of CPD-containing single-stranded DNA (ssDNA)
      on the CPD photolyase. In addition, chemical shift perturbation analyses, using
      stable isotope-labeled DNA, revealed that the CPD is buried in a cavity within
      CPD photolyase. Finally, NMR analyses of a double-stranded DNA (dsDNA)-CPD
      photolyase complex indicated that the CPD is flipped out of the dsDNA by the
      enzyme, to gain access to the active site.

PMID- 15169781
TI  - Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels:
      unexpected contributions from differences in the IV/S3-S4 outer loop.
AB  - Sea anemones are an important source of various biologically active peptides, and
      it is known that ATX-II from Anemonia sulcata slows sodium current inactivation.
      Using six different sodium channel genes (from Nav1.1 to Nav1.6), we investigated
      the differential selectivity of the toxins AFT-II (purified from Anthopleura
      fuscoviridis) and Bc-III (purified from Bunodosoma caissarum) and compared their
      effects with those recorded in the presence of ATX-II. Interestingly, ATX-II and
      AFT-II differ by only one amino acid (L36A) and Bc-III has 70% similarity. The
      three toxins induced a low voltage-activated persistent component primarily in
      the Nav1.3 and Nav1.6 channels. An analysis showed that the 18 dose-response
      curves only partially fit the hypothesized binding of Lys-37 (sea anemone toxin
      Anthopleurin B) to the Asp (or Glu) residue of the extracellular IV/S3-S4 loop in
      cardiac (or nervous) Na+ channels, thus suggesting the substantial contribution
      of some nearby amino acids that are different in the various channels. As these
      channels are atypically expressed in mammalian tissues, the data not only suggest
      that the toxicity is highly dependent on the channel type but also that these
      toxins and their various physiological effects should be considered prototype
      models for the design of new and specific pharmacological tools.

PMID- 15169783
TI  - Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA.
AB  - Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut
      transcription factors (also known as OC-1) and is essential for the development
      of the mouse pancreas, gall bladder, and the interhepatic bile ducts. HNF-6 binds
      to DNA as a monomer utilizing a single cut domain and a divergent homeodomain
      motif located at its C terminus. Here, we have used NMR methods to determine the
      solution structures of the 162 amino acid residue DNA-binding domain of the HNF
      6alpha protein. The resulting overall structure of HNF-6alpha has two different
      distinct domains: the Cut domain and the Homeodomain connected by a long flexible
      linker. Our NMR structure shows that the Cut domain folds into a topology
      homologous to the POU DNA-binding domain, even though the sequences of these two
      protein families do not show homology. The DNA contact sequence of the HNF-6alpha
      was mapped with chemical shift perturbation methods. Our data also show that a
      proposed CREB-binding protein histone acetyltransferase protein-recruiting
      sequence, LSDLL, forms a helix and is involved in the hydrophobic core of the Cut
      domain. The structure implies that this sequence has to undergo structural
      changes when it interacts with CREB-binding protein.

PMID- 15169782
TI  - Paracrine and autocrine functions of brain-derived neurotrophic factor (BDNF) and
      nerve growth factor (NGF) in brain-derived endothelial cells.
AB  - Brain-derived neurotrophic factor (BDNF) is expressed by endothelial cells. We
      investigated the characteristics of BDNF expression by brain-derived endothelial
      cells and tested the hypothesis that BDNF serves paracrine and autocrine
      functions affecting the vasculature of the central nervous system. In addition to
      expressing TrkB and p75NTR and BDNF under normoxic conditions, these cells
      increased their expression of BDNF under hypoxia. While the expression of TrkB is
      unaffected by hypoxia, TrkB exhibits a base-line phosphorylation under normoxic
      conditions and an increased phosphorylation when BDNF is added. TrkB
      phosphorylation is decreased when endogenous BDNF is sequestered by soluble TrkB.
      Exogenous BDNF elicits robust angiogenesis and survival in three-dimensional
      cultures of these endothelial cells, while sequestration of endogenous BDNF
      caused significant apoptosis. The effects of BDNF engagement of TrkB appears to
      be mediated via the phosphatidylinositol (PI) 3-kinase-Akt pathway. Modulation of
      BDNF levels directly correlate with Akt phosphorylation and inhibitors of PI 3
      kinase abrogate the BDNF responses. BDNF-mediated effects on endothelial cell
      survival/apoptosis correlated directly with activation of caspase 3. These
      endothelial cells also express p75NTR and respond to its preferred ligand, pro
      nerve growth factor (pro-NGF), by undergoing apoptosis. These data support a role
      for neurotrophins signaling in the dynamic maintenance/differentiation of central
      nervous system endothelia.

PMID- 15169784
TI  - Upstream determinants of estrogen receptor-alpha regulation of metastatic tumor
      antigen 3 pathway.
AB  - Although recent studies have shown a role of estrogen receptor-alpha (ER) in the
      regulation of epithelial-to-mesenchymal transition via MTA3, the role of upstream
      determinants of ER regulation of MTA3 and the underlying molecular mechanism
      remains unknown. Here we show that MTA3 gene regulation by ER is influenced by
      dynamic changes in levels of nuclear coregulators. MTA3 promoter has a functional
      ER element half-site with which MTA1 and HDACs interact under basal conditions.
      Upon estrogen stimulation, these corepressors are derecruited with concomitant
      recruitment of ER, leading to increased MTA3 transcription and expression.
      Genetic inactivation of MTA1 pathway promotes the ability of ER to up-regulate
      MTA3 expression, whereas knockdown of ER enhances MTA1 association with MTA3
      gene. Modulation of ER functions, by corepressors (i.e. MTA1 and MTA1s) or
      coactivators (i.e. AIB1 and PELP1/MNAR), alters ER recruitment to MTA3 chromatin,
      MTA3 transcription, and expression of downstream epithelial-to-mesenchymal
      transition components. These studies provide novel insights into the
      transregulation of the MTA3 gene and reveal novel roles of upstream determinants
      in modifying the outcome of MTA3 axis and cell differentiation.

PMID- 15169785
TI  - Two periplasmic disulfide oxidoreductases, DsbA and SrgA, target outer membrane
      protein SpiA, a component of the Salmonella pathogenicity island 2 type III
      secretion system.
AB  - The formation of disulfide is essential for the folding, activity, and stability
      of many proteins secreted by Gram-negative bacteria. The disulfide
      oxidoreductase, DsbA, introduces disulfide bonds into proteins exported from the
      cytoplasm to periplasm. In pathogenic bacteria, DsbA is required to process
      virulence determinants for their folding and assembly. In this study, we examined
      the role of the Dsb enzymes in Salmonella pathogenesis, and we demonstrated that
      DsbA, but not DsbC, is required for the full expression of virulence in a mouse
      infection model of Salmonella enterica serovar Typhimurium. Salmonella strains
      carrying a dsbA mutation showed reduced function mediated by type III secretion
      systems (TTSSs) encoded on Salmonella pathogenicity islands 1 and 2 (SPI-1 and
      SPI-2). To obtain a more detailed understanding of the contribution of DsbA to
      both SPI-1 and SPI-2 TTSS function, we identified a protein component of the SPI
      2 TTSS apparatus affected by DsbA. Although we found no substrate protein for
      DsbA in the SPI-1 TTSS apparatus, we identified SpiA (SsaC), an outer membrane
      protein of SPI-2 TTSS, as a DsbA substrate. Site-directed mutagenesis of the two
      cysteine residues present in the SpiA protein resulted in the loss of SPI-2
      function in vitro and in vivo. Furthermore, we provided evidence that a second
      disulfide oxidoreductase, SrgA, also oxidizes SpiA. Analysis of in vivo mixed
      infections demonstrated that a Salmonella dsbA srgA double mutant strain was more
      attenuated than either single mutant, suggesting that DsbA acts in concert with
      SrgA in vivo.

PMID- 15169787
TI  - Structural basis for the co-activation of protein kinase B by T-cell leukemia-1
      (TCL1) family proto-oncoproteins.
AB  - Chromosomal translocations leading to overexpression of p14(TCL1) and its
      homologue p13(MTCP1) are hallmarks of several human T-cell malignancies (1).
      p14(TCL1)/p13(MTCP1) co-activate protein kinase B (PKB, also named Akt) by
      binding to its pleckstrin homology (PH) domain, suggesting that
      p14(TCL1)/p13(MTCP1) induce T-cell leukemia by promoting anti-apoptotic signals
      via PKB (2, 3). Here we combined fluorescence anisotropy, NMR, and small angle x
      ray-scattering measurements to determine the affinities, molecular interfaces,
      and low resolution structure of the complex formed between PKBbeta-PH and
      p14(TCL1)/p13(MTCP1). We show that p14(TCL1)/p13(MTCP1) target PKB-PH at a site
      that has not yet been observed in PH-protein interactions. Located opposite the
      phospholipid binding pocket and distal from known protein-protein interaction
      sites on PH domains, the binding of dimeric TCL1 proteins to this site would
      allow the crosslinking of two PKB molecules at the cellular membrane in a
      preactivated conformation without disrupting certain PH-ligand interactions. Thus
      this interaction could serve to strengthen membrane association, promote trans
      phosphorylation, hinder deactivation of PKB, and involve PKB in a multi-protein
      complex, explaining the array of known effects of TCL1. The binding sites on both
      proteins present attractive drug targets against leukemia caused by TCL1
      proteins.

PMID- 15169786
TI  - Apolipoprotein E receptors mediate neurite outgrowth through activation of p44/42
      mitogen-activated protein kinase in primary neurons.
AB  - Several ligands of the endocytic low density lipoprotein receptor-related protein
      (LRP), such as apoE-containing lipoproteins and activated alpha2-macroglobulin
      (alpha2M*), promote neurite outgrowth, suggesting that LRP may have signaling
      functions. In this study, we found that the treatment of neurons with alpha2M*
      significantly increased the individual length (by 71%) and numbers (by 139%) of
      neurites of primary mouse cortical neurons. These effects were blocked by the LRP
      antagonist, the receptor-associated protein. We found similar neurite outgrowth
      with purified apoE3 and a tandem apoE peptide containing only the receptor
      binding domain. To investigate the intracellular pathway of the LRP signaling
      involved in neurite outgrowth, we tested the effects of alpha2M* on the
      phosphorylation of the mitogen-activated protein (MAP) extracellular signal
      regulated kinases 1 and 2 (ERK1/2). We found that 1) phospho-MAP kinase levels
      were altered within 30 min after treatment with alpha2M*, 2) the MAP kinase
      inhibitor, PD98059, specifically blocked the alpha2M*-induced neurite outgrowth,
      3) manipulating intracellular calcium by BayK or BAPTA altered the neurite
      outgrowth and associated changes in the phospho-MAP kinase levels, which were
      blunted by alpha2M*, 4) alpha2M* promoted the phosphorylation of the
      transcription factor CREB through MAP kinase, and 5) LRP-specific antibodies
      increased levels of phosphorylated MAP kinase and phosphorylated CREB. The
      effects of alpha2M*, apoE3, and apoE peptides increased LRP levels in the
      cortical neurons, whereas LRP receptor-associated protein reduced dendritic LRP
      expression. These results demonstrate that p44/42 MAP kinase plays an important
      role in LRP-mediated neurite outgrowth with activation involving the effects on
      calcium homeostasis and downstream effects involving the activation of gene
      transcription through CREB.

PMID- 15169788
TI  - Channel gating of the glycine receptor changes accessibility to residues
      implicated in receptor potentiation by alcohols and anesthetics.
AB  - The glycine receptor is a target for both alcohols and anesthetics, and certain
      amino acids in the alpha1 subunit transmembrane segments (TM) are critical for
      drug effects. Introducing larger amino acids at these positions increases the
      potency of glycine, suggesting that introducing larger residues, or drug
      molecules, into the drug-binding cavity facilitates channel opening. A possible
      mechanism for these actions is that the volume of the cavity expands and
      contracts during channel opening and closing. To investigate this hypothesis,
      mutations for amino acids in TM1 (I229C) and TM2 (G256C, T259C, V260C, M263C,
      T264C, S267C, S270C) and TM3 (A288C) were individually expressed in Xenopus
      laevis oocytes. The ability of sulfhydryl-specific alkyl methanethiosulfonate
      (MTS) compounds of different lengths to covalently react with introduced
      cysteines in both the closed and open states of the receptor was determined.
      S267C was accessible to short chain (C3-C8) MTS in both open and closed states,
      but was only accessible to longer chain (C10-C16) MTS compounds in the open
      state. Reaction with S267C was faster in the open state. I229C and A288C showed
      state-dependent reaction with MTS only in the presence of agonist. M263C and
      S270C were also accessible to MTS labeling. Mutated residues more intracellular
      than M263C did not react, indicating a floor of the cavity. These data
      demonstrate that the conformational changes accompanying channel gating increase
      accessibility to amino acids critical for drug action in TM1, TM2, and TM3, which
      may provide a mechanism by which alcohols and anesthetics can act on glycine (and
      likely other) receptors.

PMID- 15169789
TI  - Different requirements for the cytostatic and apoptotic effects of type I
      interferons. Induction of apoptosis requires ARF but not p53 in osteosarcoma cell
      lines.
AB  - The regulation of cell growth is one of the most important effects of type I
      interferons (IFNs). This response may involve a cytostatic effect or the
      induction of apoptosis depending on the cell context. Often the growth-inhibitory
      response of type I IFNs is studied in tumor cell lines carrying mutations of
      tumor suppressor genes, and therefore, the growth-inhibitory effect can be
      influenced by inactivation of these important regulators of cell proliferation.
      In this report, we explored the role of the ARF-p53 pathway in the growth
      inhibitory effect of type I IFNs. We found that p53 is only induced in cells that
      express p14(ARF) (p19(ARF) in mouse cells). Surprisingly, mouse embryonal
      fibroblasts that are null for p19(ARF) or P53, even after transformation with
      oncogenic RAS, respond as well as wild type to the growth-inhibitory effect of
      type I IFNs. Similarly, human ARF(-/-) U2OS and P53(-/-) SAOS-2 cells show a
      significant decrease in cell proliferation. However, only SAOS-2 or U2OS
      reconstituted with inducible p14(ARF) undergo apoptosis in response to IFN beta
      treatment, and this effect was not inhibited by expression of dominant negative
      p53. These data suggest that (i) at least in specific cell types, the induction
      of apoptosis by type I IFNs requires an ARF pathway that is p53-independent and
      (ii) the cytostatic and pro-apoptotic effects of type I IFNs employ different
      pathways.

PMID- 15169790
TI  - The PSI-O subunit of plant photosystem I is involved in balancing the excitation
      pressure between the two photosystems.
AB  - PSI-O is a subunit of photosystem I in eukaryotes. The function of PSI-O was
      characterized in Arabidopsis plants using RNA interference. Several transformants
      with the psaO-RNAi construct were generated, and a high proportion of the plants
      contained only very little or virtually no residual PSI-O. Plants lacking PSI-O
      have a 50% reduction in state transitions indicating a role for PSI-O in the
      balancing of excitation energy between the two photosystems. PSI-H and -L have
      been shown previously to be involved in state transitions, and immunoblot
      analysis revealed that plants devoid of PSI-L or -H also have 80-90% reduction in
      the abundance of PSI-O. In contrast, down-regulation of PSI-O has no negative
      effect on the content of PSI-H and -L. The interaction between PSI-O and the PSI
      L was confirmed by chemical cross-linking. A model of PSI is proposed in which
      PSI-L as the most ancient subunit is closest to the reaction center, and PSI-O is
      positioned close to PSI-L on the PSI-H/-L/-I side of the PSI complex. PSI-H, -L, 
      O, and possibly -I are all involved in forming a domain in PSI that is involved
      in the interaction with light-harvesting complex II.

PMID- 15169791
TI  - Endotoxin inhibits intestinal epithelial restitution through activation of Rho
      GTPase and increased focal adhesions.
AB  - Diseases of gut inflammation such as neonatal necrotizing enterocolitis (NEC)
      result after an injury to the mucosal lining of the intestine, leading to
      translocation of bacteria and endotoxin (lipopolysaccharide). Intestinal mucosal
      defects are repaired by the process of intestinal restitution, during which
      enterocytes migrate from healthy areas to sites of injury. In an animal model of
      NEC, we determined that intestinal restitution was significantly impaired
      compared with control animals. We therefore sought to determine the mechanisms
      governing enterocyte migration under basal conditions and after an endotoxin
      challenge. Here we show that the cytoskeletal reorganization and stress fiber
      formation required for migration in IEC-6 enterocytes requires RhoA. Enterocytes
      were found to express the endotoxin receptor Toll-like receptor 4, which served
      to bind and internalize lipopolysaccharide. Strikingly, endotoxin treatment
      significantly inhibited intestinal restitution, as measured by impaired IEC-6
      cell migration across a scraped wound. Lipopolysaccharide was found to increase
      RhoA activity in a phosphatidylinositol 3-kinase-dependent manner, leading to an
      increase in phosphorylation of focal adhesion kinase and an enhanced number of
      focal adhesions. Importantly, endotoxin caused a progressive, RhoA-dependent
      increase in cell matrix tension/contractility, which correlated with the observed
      impairment in enterocyte migration. We therefore conclude that endotoxin inhibits
      enterocyte migration through a RhoA-dependent increase in focal adhesions and
      enhanced cell adhesiveness, which may participate in the impaired restitution
      observed in experimental NEC.

PMID- 15169792
TI  - Signal transducer and activator of transcription-5 activation and breast cancer
      prognosis.
AB  - PURPOSE: Transcription factor signal transducer and activator of transcription-5
      (Stat5) promotes breast epithelial cell differentiation. We retrospectively
      analyzed whether levels of active Stat5 in breast cancer were linked to clinical
      outcome. MATERIALS AND METHODS: Immunohistochemistry was used to detect active,
      tyrosine-phosphorylated Stat5 in paraffin-embedded breast cancer specimens from
      three archival tissue microarray materials A, B, and C. Material A included 19
      healthy human breast tissues and a progression series of primary lymph node
      negative, primary lymph node-positive, and metastatic breast cancer (n = 400).
      Materials B (n = 785) and C (n = 570) represented two independent arrays of
      unselected primary breast cancer specimens with clinical follow-up data. RESULTS:
      Material A demonstrated that Stat5 activation, but not Stat5 protein expression,
      was gradually lost during cancer progression, with detectable activation in 100%
      of healthy breast specimens compared with less than 20% of node-positive breast
      cancers and metastases. Stat5 activation in tumors of material B was associated
      with favorable prognosis. This observation was confirmed and extended in material
      C to include both breast cancer-specific survival and disease-free survival.
      Stat5 activation remained an independent prognostic marker after adjusting for
      patient age, tumor size, histological grade, estrogen receptor, progesterone
      receptor, and Her2/neu status by Cox multivariate analysis (hazard ratio, 2.0; P
      =.029). Stat5 activation was a particularly favorable marker in the lymph node
      negative breast cancer subpopulation (hazard ratio, 7.5; P =.003). CONCLUSION: In
      our study, active Stat5 distinguishes breast cancer patients with favorable
      prognosis, and may be a useful marker for selection of more individualized
      treatment, especially in localized disease. These findings require confirmation
      in a large prospective study.

PMID- 15169793
TI  - Failure of higher-dose paclitaxel to improve outcome in patients with metastatic
      breast cancer: cancer and leukemia group B trial 9342.
AB  - PURPOSE: Cancer and Leukemia Group B Protocol 9342 was initiated to determine the
      optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to
      women with metastatic breast cancer. PATIENTS AND METHODS: Four hundred seventy
      four women with metastatic breast cancer who had received one or no prior
      chemotherapy regimens were randomly assigned to one of three paclitaxel dosing
      regimens-175 mg/m(2), 210 mg/m(2), or 250 mg/m(2)-each administered as a 3-hour
      infusion every 3 weeks. Women completed self-administered quality of life and
      symptom assessment questionnaires at baseline and after three cycles of
      treatment. RESULTS: No evidence of a significant dose-response relationship was
      demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21%
      for the three regimens, respectively. A marginally significant association (P
      =.04) was seen between dose and time to progression; however, in a multivariate
      analysis, the difference was even less apparent. No statistically significant
      difference was seen in survival. Neurotoxicity and hematologic toxicity were more
      severe on the higher dose arms. There was no significant difference in quality of
      life on the three arms. CONCLUSION: Higher doses of paclitaxel administered as a
      3-hour infusion to women with metastatic breast cancer did not improve response
      rate, survival, or quality of life. There was a slight improvement in time to
      progression with higher dose therapy, which was offset by greater toxicity. When
      a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m(2) should
      be considered the optimal dose.

PMID- 15169794
TI  - Phase II study of capecitabine in patients with fluorouracil-resistant metastatic
      colorectal carcinoma.
AB  - PURPOSE: Capecitabine is an oral fluoropyrimidine converted to fluourouracil (FU)
      preferentially in tumor tissue. It has proven clinical activity against
      colorectal cancer when used as first-line therapy. The objectives of this study
      were to assess the safety and efficacy of capecitabine in patients with
      metastatic colorectal carcinoma who progressed despite previous FU therapy.
      PATIENTS AND METHODS: According to the group sequential analysis design of this
      study, accrual would stop if no responses were observed in the first 20 patients
      treated. If one or more objective responses were confirmed, the trial would be
      expanded. Patients received capecitabine 1,250 mg/m(2) twice a day for 14 days,
      every 3 weeks. Tumor lesions were assessed every 6 weeks, and patients were
      followed for survival every 3 months after completing treatment. RESULTS: Twenty
      three patients were enrolled onto the study; 22 fulfilled all the eligibility
      criteria. No objective responses were observed among the 22 eligible patients; 11
      patients (50%) had stable disease for a median duration of 141 days (range, 88
      289 days). The Kaplan-Meier estimate of median time to disease progression was 64
      days (95% CI, 41 to 134 days). The median survival time estimate was 389 days
      (95% CI, 267 to 637 days). The most frequent treatment-related adverse events
      were hand-foot syndrome, diarrhea, and nausea or vomiting. There were no grade 4
      toxicities and no treatment-related deaths. CONCLUSION: Single-agent capecitabine
      in patients with metastatic colorectal carcinoma refractory to FU showed no
      objective responses and clinical benefit that was, at best, modest. The use of
      capecitabine in combination with other treatments in this patient population is
      under investigation.

PMID- 15169795
TI  - XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients
      with metastatic colorectal cancer.
AB  - PURPOSE: Capecitabine has demonstrated high efficacy as first-line treatment for
      metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil
      (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus
      oxaliplatin), established in a previous dose-finding study, should improve on
      infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies
      further characterize efficacy and safety of the XELOX regimen. PATIENTS AND
      METHODS: The antitumor activity of XELOX was investigated in a colon cancer
      xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment
      cycles: intravenous oxaliplatin 130 mg/m(2) (day 1) followed by oral capecitabine
      1,000 mg/m(2) twice daily (day 1, evening, to day 15, morning). RESULTS: A
      preclinical study confirmed that capecitabine has supra-additive activity with
      oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective
      response, and 30 (31%) experienced disease stabilization for >/= 3 months
      following treatment. After 24 months' minimum follow-up, median time to disease
      progression (TTP) and median overall survival were 7.7 and 19.5 months,
      respectively. XELOX safety was predictable and similar to the FOLFOX4 regimen,
      except that myelosuppression was uncommon with XELOX (grade 3 or 4 neutropenia,
      7%). Most adverse events were mild to moderate, the most common being acute
      sensory neuropathy (85%). Sixty-day, all-cause mortality was 2%. CONCLUSION:
      XELOX is a highly effective first-line treatment for MCRC. Response rates, TTP,
      and overall survival are similar to those observed with FU/leucovorin/oxaliplatin
      combinations. XELOX provides a more convenient regimen, likely to be preferred by
      both patients and healthcare providers. Capecitabine has the potential to replace
      FU/LV in combination with oxaliplatin for MCRC.

PMID- 15169796
TI  - Temozolomide for the treatment of brain metastases associated with metastatic
      melanoma: a phase II study.
AB  - PURPOSE: Temozolomide is a well-tolerated oral alkylating agent with activity in
      the CNS. A multicenter, open-label, phase II study was conducted to assess the
      safety and efficacy of temozolomide in patients with brain metastases from
      metastatic melanoma (MM) who did not require immediate radiotherapy. PATIENTS AND
      METHODS: Eligible patients had histologically confirmed MM to the brain, and no
      prior radiotherapy or radiosurgery for brain metastases. Previously untreated
      patients received temozolomide at 200 mg/m(2)/d x 5 days; previously treated
      patients received 150 mg/m(2)/d x 5 days every 28 days. Treatment continued for 1
      year or until disease progression or unacceptable toxicity. RESULTS: Of 151
      patients enrolled, 117 had received no prior systemic chemotherapy, and 34 had
      received prior chemotherapy for MM. Among previously untreated patients, 25% had
      more than four brain lesions, eight (7%) achieved an objective response (one
      complete and seven partial), and 34 (29%) had stable disease in brain metastases.
      Median overall survival was 3.5 months. Among previously treated patients, 21%
      had more than four brain lesions, one had a partial response, and six (18%) had
      stable disease in brain metastases. Median overall survival was 2.2 months.
      Temozolomide was well tolerated, with four (3%) patients discontinuing because of
      adverse events. Grade 3/4 hematologic toxicities included thrombocytopenia (3%),
      neutropenia (2%), and leukopenia (1%). Headache (9%) and vomiting (8%) were the
      most common nonhematologic grade 3/4 adverse events. CONCLUSION: Temozolomide was
      well tolerated and demonstrated activity in the treatment of brain metastases
      from MM. Further evaluation of temozolomide combination therapy is warranted.

PMID- 15169797
TI  - Phase I trial of the proteasome inhibitor bortezomib in patients with advanced
      solid tumors with observations in androgen-independent prostate cancer.
AB  - PURPOSE: To determine the dose-limiting toxicity and maximum-tolerated dose of
      the proteasome inhibitor bortezomib administered intravenously weekly for 4 every
      5 weeks; to determine the bortezomib pharmacokinetics and pharmacodynamics using
      plasma levels and an assay for 20S proteasome inhibition (PI) in whole blood; to
      correlate toxicity with bortezomib dose and degree of 20S PI; and to conduct a
      preliminary determination of the antitumor activity of bortezomib in patients
      with androgen independent prostate cancer (AIPCa). PATIENTS AND METHODS: Fifty
      three patients (48 with AIPCa) received 128 cycles of bortezomib in doses ranging
      from 0.13 to 2.0 mg/m(2)/dose, utilizing a careful escalation scheme with a
      continuous reassessment method. Pharmacokinetic and pharmacodynamic studies were
      performed in 24 patients (at 1.45 to 2.0 mg/m(2)). RESULTS: A dose-related 20S PI
      was seen, with dose-limiting toxicity at 2.0 mg/m(2) (diarrhea, hypotension)
      occurring at an average 1-hour post-dose of >/= 75% 20S PI. Other side effects
      were fatigue, hypertension, constipation, nausea, and vomiting. No relationship
      was seen between body-surface area and bortezomib clearance over the narrow dose
      range tested. There was evidence of biologic activity (decline in serum prostate
      specific antigen and interleukin-6 levels) at >/= 50% 20S PI. Two patients with
      AIPCa had prostate-specific antigen response and two patients had partial
      response in lymph nodes. CONCLUSION: The maximum-tolerated dose and recommended
      phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity
      (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is
      seen in AIPCa at tolerated doses of bortezomib. This agent should be further
      explored with chemotherapy agents in advanced prostate cancer.

PMID- 15169798
TI  - Phase II randomized study of vaccine treatment of advanced prostate cancer
      (E7897): a trial of the Eastern Cooperative Oncology Group.
AB  - PURPOSE: A phase II clinical trial was conducted to evaluate the feasibility and
      tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox
      virus expressing human prostate-specific antigen (PSA) in patients with
      biochemical progression after local therapy for prostate cancer. The induction of
      PSA-specific immunity was also evaluated. PATIENTS AND METHODS: A randomized
      clinical trial was conducted by the Eastern Cooperative Oncology group and 64
      eligible patients were randomly assigned to receive four vaccinations with
      fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA)
      vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end
      point was PSA response at 6 months, and immune monitoring included measurements
      of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses.
      RESULTS: The prime/boost schedule was well tolerated with few adverse events. Of
      the eligible patients, 45.3% of men remained free of PSA progression at 19.1
      months and 78.1% demonstrated clinical progression-free survival. There was a
      trend favoring the treatment group that received a priming dose of rV-PSA.
      Although no significant increases in anti-PSA antibody titers were detected, 46%
      of patients demonstrated an increase in PSA-reactive T-cells. CONCLUSION: Therapy
      with poxviruses expressing PSA and delivered in a prime/boost regimen was
      feasible and associated with minimal toxicity in the cooperative group setting. A
      significant proportion of men remained free of PSA and clinical progression after
      19 months follow-up, and nearly half demonstrated an increase in PSA-specific T
      cell responses. Phase III studies are needed to define the role of vaccination in
      men with prostate cancer or those who are at risk for the disease.

PMID- 15169799
TI  - Ki-67 staining is a strong predictor of distant metastasis and mortality for men
      with prostate cancer treated with radiotherapy plus androgen deprivation:
      Radiation Therapy Oncology Group Trial 92-02.
AB  - PURPOSE: The Ki-67 staining index (Ki67-SI) has been associated with prostate
      cancer patient outcome; however, few studies have involved radiotherapy (RT) 
      treated patients. The association of Ki67-SI to local failure (LF), biochemical
      failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall
      death (OD) was determined in men randomly assigned to short term androgen
      deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. PATIENTS
      AND METHODS: There were 537 patients (35.5%) on Radiation Therapy Oncology Group
      (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was
      96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be
      related to patient outcome and were examined here in a Cox proportional hazards
      multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable.
      Covariates were dichotomized in accordance with stratification and randomization
      criteria. RESULTS: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no
      difference in the distribution of patients in the Ki-67 analysis cohort (n = 537)
      and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end
      points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF
      (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric
      variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The
      7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67
      SI was the most significant correlate of DM and CSD. A detailed analysis of the
      hazard rates for DM in all possible covariate combinations revealed subgroups of
      patients treated with STAD + RT that did not require LTAD. CONCLUSION: Ki67-SI
      was the most significant determinant of DM and CSD and was also associated with
      OD. The Ki67-SI should be considered for the stratification of patients in future
      trials.

PMID- 15169801
TI  - Adjuvant chemotherapy with paclitaxel and carboplatin in patients with advanced
      carcinoma of the upper urinary tract: a study by the Hellenic Cooperative
      Oncology Group.
AB  - PURPOSE: Radical surgery represents the treatment of choice for carcinoma of the
      upper urinary tract. Nevertheless, approximately 50% of patients with stage T >/=
      3 or lymph node involvement die from their disease, mainly as a result of the
      development of distant metastases. Therefore, there is a need for effective
      adjuvant systemic treatment. We prospectively studied a cohort of patients who
      underwent surgery for high-risk carcinoma of the upper urinary tract to assess
      the feasibility of the combination of paclitaxel and carboplatin as adjuvant
      treatment. PATIENTS AND METHODS: Thirty-six patients with tumor stage >/= 3 or
      lymph node involvement were treated with four cycles of paclitaxel at 175 mg/m(2)
      and carboplatin (area under the curve 5, Calvert Formula) every 3 weeks following
      surgery. RESULTS: Median follow-up was 40.6 months. Chemotherapy was well
      tolerated with 32 patients (89%) receiving full carboplatin and paclitaxel doses
      without delays. The most frequent grade 3/4 toxicity was neutropenia (39%), which
      was complicated with fever in only one case (3%). Nonhematologic grade 3 or 4
      toxicities were reported in only one case. Five-year survival was 52% (95% CI,
      35% to 69%), while 5-year disease-free survival was 40.2% (95% CI, 15.8% to
      64.6%). Local failure rate was 30%, as opposed to 17% of patients who developed
      distant metastases. No patients with grade 2 tumors relapsed during follow-up, as
      opposed to 60% of patients with grade 3 tumors. CONCLUSION: Adjuvant chemotherapy
      with paclitaxel and carboplatin is feasible and may reduce the risk of distant
      metastases in high-risk upper urinary tract carcinoma.

PMID- 15169800
TI  - The changing face of low-risk prostate cancer: trends in clinical presentation
      and primary management.
AB  - PURPOSE: Early intervention for prostate cancer is associated with excellent long
      term survival, but many affected men, especially those with low-risk disease
      characteristics, might not experience adverse impact to survival or quality of
      life were treatment deferred. We sought to characterize temporal trends in
      clinical presentation and primary disease management among patients with low-risk
      prostate cancer. METHODS: Data were abstracted from the Cancer of the Prostate
      Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 8,685 men
      with various stages of prostate cancer. Included were 2,078 men who were
      diagnosed between 1989 and 2001 and had a serum prostate specific antigen </= 10
      ng/mL, Gleason sum </= 6, and clinical T stage </= 2a. Trends in risk
      distribution, tumor characteristics, and primary treatment were evaluated.
      RESULTS: The proportion of patients with low-risk tumor characteristics rose from
      29.8% in 1989 to 1992, to 45.3% in 1999 to 2001 (P <.0001). There have been sharp
      increases in the use of brachytherapy and androgen deprivation monotherapy, from
      3.1% and 3.1%, to 12.0% and 21.7%, respectively. Utilization rates for
      prostatectomy, external-beam radiotherapy, and observation have fallen
      accordingly, from 63.8%, 16.1%, and 13.8%, to 51.6%, 6.8%, and 7.9% (P <.0001 for
      all except prostatectomy [P =.0019]). Age and socioeconomic status were
      significantly associated with treatment selection, but overall, the treatment
      trends were echoed on subgroup analysis of patients 75 years or older.
      CONCLUSION: Low-risk features characterize a growing proportion of prostate
      cancer patients, and there have been significant shifts in the management of low
      risk disease. Overtreatment may be a growing problem, especially among older
      patients.

PMID- 15169802
TI  - Secondary leukemias in refractory germ cell tumor patients undergoing autologous
      stem-cell transplantation using high-dose etoposide.
AB  - PURPOSE: To quantify the risk of secondary leukemias in relapsed testicular
      cancer patients undergoing autologous stem-cell transplantation with high-dose
      etoposide. PATIENTS AND METHODS: Single institution, retrospective study of germ
      cell tumor patients who underwent autologous transplantation using high-dose
      etoposide from 1987 to 2001. RESULTS: One hundred thirteen patients received high
      dose etoposide and carboplatin followed by autologous stem-cell transplantations
      for germ cell tumors. Follow-up ranged from 12 to 166 months (median, 51 months).
      Three patients (2.6%; 95% CI, 0.55% to 7.50%) subsequently developed leukemia at
      an average of 16 months post-autologous transplantation (range, 11 to 21 months).
      All three had received tandem transplantations and had been heavily pretreated,
      including at least one prior cycle of etoposide. Following autologous
      transplantation, all three patients exhibited refractory cytopenias before
      developing overt leukemia. All leukemias were of myeloid lineage. One patient
      developed an M2 with a t(8,21) chromosomal translocation; another, an M5 with a
      t(11,19); and one patient exhibited an unclassified leukemia with cytogenetic
      abnormalities resulting in monosomy for 7p and partial monosomy of 7q. Treatment
      of the leukemias involved allogeneic bone marrow transplantation. CONCLUSION:
      High-dose chemotherapy using high-dose etoposide as therapy for relapsed germ
      cell tumors was associated with a 2.6% risk of developing a secondary myeloid
      leukemia. This figure was not significantly different from the expected rate of
      secondary leukemias when patients receive additional cycles of standard-dose
      etoposide as salvage chemotherapy for germ cell tumors. Other factors, including
      the use of platinum agents, may also have a role in leukemogenesis in this
      patient population.

PMID- 15169803
TI  - Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus
      filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.
AB  - PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus
      cisplatin improves overall survival (OS) in women with advanced or recurrent
      endometrial carcinoma. Secondary comparisons included progression-free survival
      (PFS), response rate (RR), and toxicities. PATIENTS AND METHODS: Eligible,
      consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2)
      (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by
      paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial
      doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior
      pelvic radiotherapy and those older than 65 years. Both regimens were repeated
      every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity
      questionnaire before each cycle. RESULTS: Two hundred seventy-three women (10
      ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median,
      8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were
      improved with TAP. Treatment was hematologically well tolerated, with only 2% of
      patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic
      fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3,
      and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in
      those receiving AP. Patient-reported neurotoxicity was significantly higher in
      the TAP arm following two cycles of therapy. CONCLUSION: TAP significantly
      improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high
      risk adjuvant setting is warranted, but close attention should be paid to the
      increased risk of peripheral neuropathy.

PMID- 15169804
TI  - Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of
      the cervix: response and outcome.
AB  - PURPOSE: The aim of this study was to evaluate response to therapy using
      posttherapy molecular imaging with [(18)F] fluorodeoxyglucose (FDG), and to
      compare the response with patient outcome. PATIENTS AND METHODS: This was a
      retrospective medical record review of 152 patients with carcinoma of the cervix.
      All patients underwent a pre- and posttreatment whole-body positron emission
      tomography (PET) imaging scan with FDG. Patients were treated with external
      irradiation and intracavitary brachytherapy, and most received concurrent weekly
      cisplatin. Posttherapy whole-body FDG-PET was performed 1 to 12 months (mean, 3
      months) after completion of treatment. RESULTS: The posttherapy PET did not show
      any abnormal FDG uptake in 114 patients, and their 5-year cause-specific survival
      estimate was 80%. There was persistent (in the irradiated region) abnormal FDG
      uptake in the cervix or lymph nodes in 20 patients. Their 5-year cause-specific
      survival estimate was 32%. New anatomic sites (in unirradiated regions) of
      abnormal FDG uptake were present in 18 patients, and none were alive at 5 years.
      A Cox proportional hazards model of survival outcome indicated that any abnormal
      posttherapy FDG uptake (persistent or new) was the most significant prognostic
      factor for developing metastatic disease and death from cervical cancer when
      compared with pretreatment- and treatment-related prognostic factors (P <.0001).
      CONCLUSION: Posttherapy abnormal FDG uptake (persistent or new) as detected by
      whole-body PET measures tumor response and might be predictive of tumor
      recurrence and death from cervical cancer. Prospective validation of these
      results is warranted.

PMID- 15169805
TI  - Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's
      lymphomas after reduced-intensity conditioning followed by allogeneic
      transplantation of hematopoietic cells.
AB  - PURPOSE: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of
      malignancies characterized by a poor prognosis. We performed a pilot study to
      investigate the role of reduced-intensity conditioning (RIC) followed by
      allogeneic stem-cell transplantation in relapsed or refractory PTCLs. PATIENTS
      AND METHODS: We have conducted a phase II trial on 17 patients receiving salvage
      chemotherapy followed by RIC and allogeneic transplantation of hematopoietic
      cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide.
      The acute graft-versus-host disease prophylaxis consisted of cyslosporine and
      short course methotrexate. RESULTS: Patients had a median age of 41 years (range,
      23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed
      disease; eight patients (47%) had a disease relapse after an autologous
      transplantation. After a median follow-up of 28 months from the day of study
      entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete
      remission, one in partial remission, and one with stable disease), two died as a
      result of progressive disease, and one died as a result of sepsis concomitant to
      acute graft-versus-host disease. The estimated 3-year overall and progression
      free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%),
      respectively. The estimated probability of nonrelapse mortality at 2 years was 6%
      (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two
      patients progressing after allografting. CONCLUSION: RIC followed by allogeneic
      stem-cell transplantation is feasible, has a low treatment-related mortality, and
      seems to be a promising salvage treatment for relapsed PTCL. These findings
      suggest that the existence of a graft-versus-T-cell lymphoma effect.

PMID- 15169806
TI  - Antiretroviral treatment regimens and immune parameters in the prevention of
      systemic AIDS-related non-Hodgkin's lymphoma.
AB  - PURPOSE: Immunosuppression induced by HIV-1 increases the risk of developing non
      Hodgkin's lymphoma (NHL). We measured the influence of immunologic factors and
      highly active antiretroviral therapy (HAART) on this risk. As there are no data
      demonstrating that specific antiretroviral regimens are effective at protecting
      from NHL, we compared different HAART regimens. PATIENTS AND METHODS: The
      protective effect of HAART regimens, containing protease inhibitors (PI) and/or
      non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the development of
      NHL was examined in a prospectively recorded cohort of 9,621 HIV-infected
      individuals. Lymphocyte and natural killer subset data were also entered in
      univariate and multivariate analyses to establish and stratify the risk of NHL.
      RESULTS: From this cohort of 9,621 patients, 102 have been diagnosed with
      systemic AIDS-related NHL since 1996, when HAART became freely available here. By
      univariate analysis, increased age, higher nadir CD4 and CD8 T-cell counts, CD19
      B-cell count, CD16/56 natural killer count and exposure to NNRTI or PI containing
      HAART conferred significant protection against NHL (P <.05). In a multivariate
      analysis, age, nadir CD4 and CD8 T-cell counts, and exposure to HAART were
      independent predictors of risk of NHL (P <.02). NNRTI-based HAART (adjusted rate
      ratio, 0.4; 95% CI, 0.3 to 0.5) was as protective as PI-based HAART, and these
      were significantly more protective than nucleoside analogues alone (rate ratio,
      0.5; 95% CI, 0.4 to 0.7) or no antiretrovirals (P <.001). CONCLUSION: Effective
      HAART-induced maintenance of CD4 and CD8 counts protects from systemic AIDS
      related NHL.

PMID- 15169807
TI  - Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel
      with carboplatin and paclitaxel alone in previously untreated locally advanced or
      metastatic non-small-cell lung cancer.
AB  - PURPOSE: To investigate the efficacy and safety of bevacizumab plus carboplatin
      and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer.
      PATIENTS AND METHODS: In a phase II trial, 99 patients were randomly assigned to
      bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the
      curve = 6) and paclitaxel (200 mg/m(2)) every 3 weeks or carboplatin and
      paclitaxel alone (n = 32). Primary efficacy end points were time to disease
      progression and best confirmed response rate. On disease progression, patients in
      the control arm had the option to receive single-agent bevacizumab 15 mg/kg every
      3 weeks. RESULTS: Compared with the control arm, treatment with carboplatin and
      paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5%
      v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest
      increase in survival (17.7 v 14.9 months). Of the 19 control patients that
      crossed over to single-agent bevacizumab, five experienced stable disease, and 1
      year survival was 47%. Bleeding was the most prominent adverse event and was
      manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and
      major hemoptysis. Major hemoptysis was associated with squamous cell histology,
      tumor necrosis and cavitation, and disease location close to major blood vessels.
      CONCLUSION: Bevacizumab in combination with carboplatin and paclitaxel improved
      overall response and time to progression in patients with advanced or recurrent
      non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be
      a subpopulation with improved outcome and acceptable safety risks.

PMID- 15169809
TI  - Estimate of lung cancer mortality from low-dose spiral computed tomography
      screening trials: implications for current mass screening recommendations.
AB  - PURPOSE: Low-dose computed tomography (CT) has been suggested for lung cancer
      screening. Several observational trials have published their preliminary results,
      and some investigators suggest that this technique will save lives. There are no
      mortality statistics, however, and the current study used published data from
      these trials to estimate the disease-specific mortality in this high-risk
      population. PATIENTS AND METHODS: Two nonrandomized CT screening trials were
      selected from the literature for analysis. The number of trial participants, the
      number of lung cancers diagnosed per year, and stage distribution of the cancers
      was recorded. Previously published 5-year survival data were used to calculate
      the number of predicted lung cancer deaths and estimate the overall lung cancer
      mortality per 1,000 person-years among participants screened. These statistics
      were then compared to the previous Mayo Lung Project, which used chest
      radiographs and sputum cytology for screening high-risk individuals. RESULTS:
      This study estimates the lung cancer mortality is 4.1 deaths per 1,000 person
      years in the Mayo Clinic CT screening trial, and is 5.5 deaths per 1,000 person
      years in the Early Lung Cancer Action Program trial. These data are similar to
      the lung cancer mortality of 4.4 deaths per 1,000 person-years in the
      interventional arm, and 3.9 deaths per 1,000 person-years in the usual-care arm
      of the previous Mayo Lung Project. CONCLUSION: These data suggest that CT
      screening could produce similar outcomes to prior chest radiographic trials in
      this high-risk group. Results from randomized trials are required, however,
      before the true utility of mass screening with CT for lung cancer can be
      determined.

PMID- 15169808
TI  - Phase II trial of pleural photodynamic therapy and surgery for patients with non
      small-cell lung cancer with pleural spread.
AB  - PURPOSE: Non-small-cell lung cancer (NSCLC) with pleural spread is incurable,
      with median survival rates ranging from 6 to 9 months. Surgery alone fails to
      locally control this disease or extend survival beyond the accepted treatment,
      palliative chemotherapy. METHODS: We conducted a phase II trial to evaluate the
      effects on local control and survival of combining surgery with intraoperative
      photodynamic therapy (PDT), a light-based cancer treatment, in patients with
      NSCLC with pleural spread. Patients received porfimer sodium (2 mg/kg), 24 hours
      before surgery, at which time all gross tumor was resected and followed by
      illumination of the hemithorax with 630 nm light to a measured dose of 30
      J/cm(2). Photosensitizer levels in tumor and surrounding normal tissue were
      measured. RESULTS: Twenty-two patients with NSCLC were enrolled; 17 underwent
      complete debulking and PDT, three underwent partial debulking/PDT, and two
      patients were unresectable. Local control of pleural disease at 6 months was
      achieved in 11 of 15 (73.3%; 95% CI, 44.9% to 92.2%) assessable patients. Median
      overall survival for all 22 patients was 21.7 months (95% CI, 17.7 to 25.8
      months). Measured levels of porfimer sodium in tumor were greater than those
      measured in normal tissues, with ratios ranging from 1.19 to 22.42. CONCLUSION:
      Our results indicate surgery and PDT can be performed safely with very good local
      control. The median survival of 21.7 months, calculated from the time of surgery
      and PDT is encouraging. Further evaluation of this therapy is warranted.

PMID- 15169810
TI  - Pentoxifylline in the treatment of radiation-induced fibrosis.
AB  - PURPOSE: Fibrotic sequelae remain the most important dose-limiting toxicity of
      radiation therapy to soft tissue. Functionally, this is reflected in loss of
      range of motion and muscle strength and the development of limb edema and pain.
      Tumor necrosis factor alpha and fibroblast growth factor 2 (FGF2), which are
      abnormally elevated in irradiated tissues, may mediate radiation fibrovascular
      injury. PATIENTS AND METHODS: In an open label drug trial, we studied the effects
      of pentoxifylline (400 mg orally tid for 8 weeks) on 30 patients who displayed
      late, radiation-induced fibrosis at 1 to 29 years posttreatment (40 to 84 Gy).
      The primary outcome measurement was change in physical impairments thought to be
      secondary to radiation, including active and passive range of motion (AROM and
      PROM), muscle strength, limb edema, and pain. Plasma levels of cytokines (tumor
      necrosis factor alpha and FGF2) also were measured. Twenty-seven patients
      completed baseline and 8-week assessments, and 24 patients completed baseline, 8
      week, and 16-week assessments. RESULTS: After 8 weeks of pentoxifylline
      intervention, 20 of 23 patients with impaired AROM and 19 of 22 with impaired
      PROM improved; 11 of 19 patients with muscle weakness showed improved motor
      strength; five of seven patients with edema had decreased limb girth; and nine of
      20 patients had decreased pain. Pretreatment FGF2 levels dropped from an average
      of 44.9 pg/mL to 24.0 pg/mL after 8 weeks of treatment. CONCLUSION: Patients
      receiving pentoxifylline demonstrated improved AROM, PROM, and muscle strength
      and decreased limb edema and pain. Reversal of these delayed radiation effects
      was associated with a decrease in circulating FGF2.

PMID- 15169811
TI  - Four decades of continuing innovation with fluorouracil: current and future
      approaches to fluorouracil chemoradiation therapy.
AB  - PURPOSE: Chemoradiotherapy, the combination of external radiation therapy and
      concurrent chemotherapy, has been the basis for the oncologic management of many
      patients since its development in the 1960s. Fluorouracil (FU) chemoradiotherapy
      has demonstrated success in several organ sites with multiple dosing schedules
      that now guide the selection of oral analogs of FU to provide new
      chemoradiotherapy options. METHODS: This article reviews the metabolism and
      pharmacology of FU and the advantages of administration of FU by continuous
      infusion or bolus. The potential role and impact of the oral fluorouracil
      prodrugs UFT, S-1, BOF-A2, and capecitabine as replacements for intravenous
      administration are discussed. The results of recent chemoradiotherapy studies
      with FU from 2000 to 2003 are summarized in rectal, head and neck, esophageal,
      gastric, pancreatic, biliary, anal, and cervical cancers. RESULTS:
      Chemoradiotherapy with FU has the potential to widen the therapeutic window by
      minimizing normal tissue toxicity while maintaining effective tumor toxicity.
      Overall, FU chemoradiotherapy maximizes local control and, for some tumor sites
      (such as head and neck, pancreatic, biliary, cervical, esophageal, and gastric
      cancers), improves survival rates. Moreover, FU chemoradiotherapy results in
      improved organ preservation with excellent functional outcome in several anatomic
      sites including head and neck cancer, anal, and rectal cancer, with improved
      sphincter preservation. CONCLUSION: FU chemoradiotherapy continues to play an
      important role in the management of many cancer sites. During the last four
      decades, optimal dosing schedules have produced a therapeutic gain. The
      introduction of oral prodrug analogs will likely further improve the results of
      FU therapy in several organ systems, such as the rectum, head and neck, and
      esophagus.

PMID- 15169812
TI  - Cognitive impairment associated with chemotherapy for cancer: report of a
      workshop.
AB  - Cognitive dysfunction may occur in some patients who receive chemotherapy. We
      provide a summary of an April 2003 workshop on this topic, that included medical
      oncologists, radiologists, clinical and experimental psychologists, and patient
      advocates. Current studies indicate that cognitive deficits are often subtle,
      although they are observed consistently in a proportion of patients, may be
      durable, and can be disabling. Deficits have been observed in a range of
      cognitive functions. Underlying mechanisms are unknown, although preliminary
      studies suggest there may be genetic predisposition and that cognitive impairment
      may be accompanied by changes in the brain detectable by neuroimaging. The
      following priorities were established for future research: (1) large-scale
      clinical studies that use both a longitudinal design and concurrent evaluation of
      patients with cancer who do not receive chemotherapy-such studies should address
      the probability and magnitude of cognitive deficits, factors that predict them,
      and underlying mechanisms; (2) exploration of discrepancies between subjective
      reports of cognitive dysfunction and the objective results of cognitive testing;
      (3) studies of cognitive function in patients receiving treatment for diseases
      other than breast cancer, and in both men and women, to address the hypothesis
      that underlying mechanisms relate to changes in serum levels of sex hormones
      and/or to chemotherapy-induced menopause; (4) development of interventions to
      alleviate these problems; and (5) development of animal models and the use of
      imaging techniques to address mechanisms that might cause cognitive impairment
      associated with chemotherapy.

PMID- 15169813
TI  - Paraneoplastic syndromes in cancer: Case 1. Polycythemia as a result of ectopic
      erythropoietin production in metastatic pancreatic carcinoid tumor.

PMID- 15169814
TI  - Paraneoplastic syndromes in cancer: Case 2. Leucocytosis associated with
      liposarcoma recurrence: original presentation of liposarcoma recurrence.

PMID- 15169815
TI  - Paraneoplastic syndromes in cancer: Case 3. Parathyroid hormone-related
      hypercalcemia in cholangiocarcinoma.

PMID- 15169816
TI  - Real-time rationing of scarce resources: the Northeast Proton Therapy Center
      experience.

PMID- 15169817
TI  - What ASCO does for its members.

PMID- 15169818
TI  - Concurrence of germline mutations in the APC and PTEN genes in a colonic
      polyposis family member.

PMID- 15169819
TI  - Cavernosal arterial insufficiency and metabolic syndrome probably represent a
      common pathology of endothelial dysfunction in recipients of high-dose therapy
      and stem-cell transplantation.

PMID- 15169820
TI  - Uncertainties regarding pelvic radiotherapy for prostate cancer.

PMID- 15169822
TI  - Internal mammary lymphatic irradiation: to be or not to be?

PMID- 15169824
TI  - Empathy in the doctor-patient relationship.

PMID- 15169828
TI  - N-methyl-D-aspartate receptor blockade inhibits cardiac inflammation in the Mg2+
      deficient rat.
AB  - Elevated plasma levels of the neuropeptide substance P (SP) precede the
      perivascular inflammatory infiltrate seen in hearts of Mg(2+)-deficient (MgD)
      animals. The N-methyl-d-aspartate (NMDA) receptor is found in neurons, and
      activation of this receptor participates in SP release; under normal
      circumstances, this release can be blocked by Mg(2+). Therefore, we reasoned that
      blockade of the NMDA receptor with dizolcipine maleate (a noncompetitive NMDA
      receptor antagonist) would prevent SP release from C-fibers due to MgD. In this
      study, animals were implanted with slow-release pellets containing dizolcipine or
      placebo and were fed with diet sufficient in Mg(2+) or deficient with only 9% of
      USDA-recommended Mg(2+). SP immunostaining of dorsal root ganglia showed a time
      dependent depletion of SP in the MgD animals, with a dramatic decrease of SP by
      week 2; this depletion was prevented by pretreatment with dizolcipine maleate.
      The significant increase in plasma prostaglandin E(2) levels during MgD was
      prevented by dizolcipine, and the loss of total red blood cell glutathione
      content was significantly attenuated by NMDA blockade after 3 weeks of MgD (p <
      0.01 versus controls). Immunohistochemical and Western blot analyses of
      ventricular tissue demonstrated that NMDA receptor blockade abolished MgD-related
      increase of endothelium adhesion molecule CD54 (weeks 1 and 2; p < 0.05), and of
      monocyte/macrophage surface protein CD11b expression (week 3; p < 0.05). We
      conclude that NMDA receptor blockade with dizolcipine maleate prevented SP
      depletion and reduced perivascular inflammatory infiltrates, thus decreasing
      cardiac injury due to Mg(2+) deficiency.

PMID- 15169827
TI  - Thioether metabolites of 3,4-methylenedioxyamphetamine and 3,4
      methylenedioxymethamphetamine inhibit human serotonin transporter (hSERT)
      function and simultaneously stimulate dopamine uptake into hSERT-expressing SK-N
      MC cells.
AB  - 3,4-Methylenedioxyamphetamine (MDA) and 3,4-methyl-enedioxymethamphetamine (MDMA,
      ecstasy) are widely abused amphetamine derivatives that target the serotonin
      system. The serotonergic neurotoxicity of MDA and MDMA seems dependent on their
      systemic metabolism. 5-(Glutathion-S-yl)-alpha-methyldopamine [5-(GSyl)-alpha
      MeDA] and 2,5-bis(glutathion-S-yl)-alpha-methyldopamine [2,5-bis(GSyl)-alpha
      MeDA], metabolites of MDA and MDMA, are also selective serotonergic
      neurotoxicants and produce behavioral and neurochemical changes similar to those
      seen with MDA and MDMA. We now show that 5-(GSyl)-alpha-MeDA and 2,5-bis(GSyl)
      alpha-MeDA are more potent than MDA and MDMA (K(i) = 69, 50, 107, and 102 microM,
      respectively) at inhibiting 5-hy-droxytryptamine (serotonin) transport into SK-N
      MC cells transiently transfected with the human serotonin transporter (hSERT).
      Moreover, 5-(GSyl)-alpha-MeDA and 2,5-bis(GSyl)-alpha-MeDA simultaneously
      stimulated dopamine (DA) transport into the hSERT-expressing cells, an effect
      attenuated by fluoxetine, indicating that stimulated DA transport was hSERT
      dependent. Finally, 5-(GSyl)-alpha-MeDA and 2,5-bis(GSyl)-alpha-MeDA, and to a
      lesser extent MDA and MDMA, induced a concentration and time-dependent increase
      in reactive oxygen species (ROS) in both hSERT and human dopamine transporter
      transfected cells. Fluoxetine attenuated the increase in ROS generation in hSERT
      expressing cells. The results are consistent with the view that the serotonergic
      neurotoxicity of MDA and MDMA may be mediated by the metabolism-dependent
      stimulation of DA transport into hSERT-expressing cells and ROS generation by
      redox active catechol-thioether metabolites and DA.

PMID- 15169829
TI  - Ligand-directed functional heterogeneity of histamine H1 receptors: novel dual
      function ligands selectively activate and block H1-mediated phospholipase C and
      adenylyl cyclase signaling.
AB  - The autacoid and neurotransmitter histamine activates the H(1) G protein-coupled
      receptor (GPCR) to stimulate predominantly phospholipase C (PLC)/inositol
      phosphate (IP) signaling and, to a lesser extent, adenylyl cyclase (AC)/cAMP
      signaling in a variety of mammalian cells and tissues, as well as H(1)
      transfected clonal cell lines. This study reports that two novel H(1) receptor
      ligands developed in our laboratory, (-)-trans-1-phenyl-3-dimethylamino-1,2,3,4
      tetrahydronaphthalene (trans-PAT) and (+/-)-cis-5-phenyl-7-dimethylamino-5,6,7,8
      tetrahydro-9H-benzocycloheptane (cis-PAB), activate H(1) receptors to selectively
      stimulate AC/cAMP formation and PLC/IP formation, respectively, in Chinese
      hamster ovary cells transfected with guinea pig H(1) receptor cDNA. trans-PAT and
      cis-PAB also are shown to be functionally selective antagonists of H(1)-linked
      PLC/IP and AC/cAMP signaling, respectively. Whereas cis-PAB H(1) receptor
      activity is shown to be typically competitive, trans-PAT displays a complex
      interaction with the H(1) receptor that is not competitive regarding antagonism
      of saturation binding by the standard H(1) antagonist radioligand
      [(3)H]mepyramine or H(1)/PLC/IP functional activation by histamine. trans-PAT,
      however, does competitively block H(1)/PLC/IP functional activation by cis-PAB.
      Molecular determinants for trans-PAT versus cis-PAB differential binding to H(1)
      receptors, which presumably leads to differential activation of AC/cAMP versus
      PLC/IP signaling, likely involves stereochemical factors as well as more subtle
      steric influences. Results suggest the trans-PAT and cis-PAB probes will be
      useful to study molecular mechanisms of ligand-directed GPCR multifunctional
      signaling. Moreover, because most untoward cardiovascular-, respiratory-, and
      gastrointestinal H(1) receptor-mediated effects proceed via the PLC/IP pathway,
      PAT-type agonists that selectively enhance H(1)-mediated AC/cAMP signaling
      provide a mechanistic basis for exploiting H(1) receptor activation for drug
      design purposes.

PMID- 15169830
TI  - Insulin signaling regulates gamma-glutamylcysteine ligase catalytic subunit
      expression in primary cultured rat hepatocytes.
AB  - Decreased glutathione (GSH) levels and gamma-glutamylcysteine ligase (GCL)
      activity have been observed in diabetic patients, and insulin reportedly
      increases GSH synthesis via increased GCL catalytic subunit (GCLC) gene
      expression. The signaling pathways responsible for mediating insulin effects on
      GCLC expression and GSH levels, however, are unknown. The signaling pathways
      involved in the regulation of GSH synthesis in response to insulin were examined
      in primary cultured rat hepatocytes. GSH levels, GCL activity, GCLC protein, and
      mRNA levels were increased to 140, 160, 600, and 340% of that monitored in
      untreated cells, respectively, in hepatocytes cultured with 100 nM insulin. The
      phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002 [2-(4
      morpholinyl)-9-phenyl-4H-1-benzopyran-4-one], dominant-negative Akt, or
      rapamycin, an inhibitor of mTOR (mammalian target of rapamycin) and ribosomal p70
      S6 kinase (p70S6K) phosphorylation, inhibited the insulin-mediated increase in
      GCLC protein and GSH levels. Although the mitogen-activated protein kinases
      (MAPKs) extracellular signal-regulated kinase, p38 MAPK, and JNK (c-Jun N
      terminal kinase) were activated in response to insulin, PD98059 (2'-amino-3'
      methoxyflavone), an inhibitor of mitogen-activated protein kinase kinase,
      SP600125 (1,9-pyrazoloanthrone), an inhibitor of JNK, and SB203580 [4-(4
      fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole], an inhibitor
      of p38 MAPK, failed to inhibit the insulin-mediated increase in GCLC protein
      levels. In conclusion, these data show that insulin signaling pathways involving
      PI3K/Akt/p70S6K, but not MAPKs, are active in the insulin-mediated regulation of
      GSH synthesis via increased GCLC expression.

PMID- 15169832
TI  - Whitewash. By Mole.

PMID- 15169831
TI  - Ethanol suppression of ventral tegmental area GABA neuron electrical transmission
      involves N-methyl-D-aspartate receptors.
AB  - Ventral tegmental area (VTA) GABA neurons are critical substrates modulating the
      mesocorticolimbic dopamine system implicated in natural and drug reward. The aim
      of this study was to evaluate the effects of ethanol on glutamatergic and
      GABAergic modulation of VTA GABA neuron electrical synaptic transmission. We
      evaluated the effects of systemic ethanol (0.05-2.0 g/kg i.p.), the N-methyl-D
      aspartate (NMDA) receptor antagonist dizocilpine (MK-801; 0.05-0.2 mg/kg i.v.),
      the connexin-36 gap junction blocker quinidine (5-20 mg/kg i.v.), the fast-acting
      barbiturate methohexital (Brevital; 5-10 mg/kg i.v.), and the benzodiazepine
      chlordiazepoxide (Librium; 5-10 mg/kg i.v.), as well as in situ VTA
      administration of NMDA and the GABA(A) receptor agonist muscimol, on VTA GABA
      neuron spontaneous activity and internal capsule stimulus-induced poststimulus
      spike discharges (ICPSDs). Systemic ethanol, quinidine, and dizocilpine reduced,
      whereas local NMDA enhanced, and the systemic and local GABA(A) receptor
      modulators did not significantly alter VTA GABA neuron ICPSDs. Ethanol
      potentiated dizocilpine inhibition of VTA GABA neuron ICPSDs, but not quinidine
      inhibition. In situ microelectrophoretic application of dopamine markedly
      enhanced VTA GABA neuron firing rate (131%), spike duration (124%), and spike
      coupling, which were blocked by systemic quinidine. These findings indicate that
      VTA GABA neurons are coupled electrically via gap junctions and that the
      inhibitory effect of ethanol on electrical transmission is primarily via
      inhibition of NMDA receptor-mediated excitation, not via enhancement of GABA
      receptor-mediated inhibition. Thus, the rewarding properties of ethanol may
      result from inhibitory effects on excitatory glutamatergic neurotransmission
      between electrically coupled networks of midbrain GABA neurons.

PMID- 15169833
TI  - nNOS at a glance: implications for brain and brawn.

PMID- 15169834
TI  - Annexins--unique membrane binding proteins with diverse functions.
AB  - Annexins are a well-known multigene family of Ca(2+)-regulated phospholipid
      binding and membrane-binding proteins. Recent work employing annexin-knockdown or
      - knockout models has provided new insights into the biological functions of
      different annexin proteins. Transient annexin depletion by RNA interference and
      the expression of dominant-negative mutant proteins has revealed roles for the
      proteins in membrane processes ranging from the control of membrane structure to
      certain membrane transport phenomena. Although such functions correlate well with
      the ability of annexins to interact with cellular membranes in a reversible and
      regulated manner, some activities are membrane independent, probably because
      annexins can also engage in specific protein-protein interactions. Among other
      things, this is evident in annexin A1- and A2-knockout mice, which show impaired
      regulation of neutrophil extravasation and defects in plasmin generation,
      respectively.

PMID- 15169835
TI  - "The stress of dying": the role of heat shock proteins in the regulation of
      apoptosis.
AB  - Heat shock proteins (Hsps) are a family of highly homologous chaperone proteins
      that are induced in response to environmental, physical and chemical stresses and
      that limit the consequences of damage and facilitate cellular recovery. The
      underlying ability of Hsps to maintain cell survival correlates with an
      inhibition of caspase activation and apoptosis that can, but does not always,
      depend upon their chaperoning activities. Several mechanisms proposed to account
      for these observations impact on both the "intrinsic", mitochondria-dependent and
      the "extrinsic", death-receptor-mediated pathways to apoptosis. Hsps can inhibit
      the activity of pro-apoptotic Bcl-2 proteins to prevent permeabilization of the
      outer mitochondrial membrane and release of apoptogenic factors. The disruption
      of apoptosome formation represents another mechanism by which Hsps can prevent
      caspase activation and induction of apoptosis. Several signaling cascades
      involved in the regulation of key elements within the apoptotic cascade are also
      subject to modulation by Hsps, including those involving JNK, NF-kappaB and AKT.
      The coordinated activities of the Hsps thus modulate multiple events within
      apoptotic pathways to help sustain cell survival following damaging stimuli.

PMID- 15169836
TI  - A screen for modifiers of RacGAP(84C) gain-of-function in the Drosophila eye
      revealed the LIM kinase Cdi/TESK1 as a downstream effector of Rac1 during
      spermatogenesis.
AB  - In Drosophila, RotundRacGAP/RacGAP(84C) is critical to retinal organisation and
      spermatogenesis. We show that eye-directed expression of RacGAP(84C) or its
      GTPase activating protein (GAP) domain induces a dominant rough eye phenotype
      which we used as a starting point in a gain-of-function screen to identify new
      partners of RacGAP(84C). Proteins known to function in Ras, Rho and Rac
      signalling were identified confirming the essential role of RacGAP(84C) in
      crosstalk between GTPases. Other potential RacGAP(84C) partners identified by the
      screen are implicated in signal transduction, DNA remodelling, cytoskeletal
      organisation, membrane trafficking and spermatogenesis. This latter class
      includes the serine/threonine kinase Center divider (Cdi), which is homologous to
      the human LIM kinase, Testis specific kinase 1 (TESK1), involved in cytoskeleton
      control through Cofilin phosphorylation. Eye-directed expression of cdi strongly
      suppressed the phenotypes induced by either RacGAP(84C) gain-of-function or by
      the dominant negative form of Rac1, Rac1N17. These results are consistent with
      Cdi being a specific downstream target of Rac1. We showed that Rac1 and cdi are
      both expressed in Drosophila testis and that homozygous Rac1 mutants exhibit poor
      fertility that is further reduced by introducing a cdi loss-of-function mutation
      in trans. Thus, results from a misexpression screen in the eye led us to a
      putative novel Rac1-Cdi-Cofilin pathway, regulated by RacGAP(84C), coordinating
      Drosophila spermatogenesis.

PMID- 15169837
TI  - LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II
      formation.
AB  - Rat LC3, a homologue of yeast Atg8 (Aut7/Apg8), localizes to autophagosomal
      membranes after post-translational modifications. The C-terminal fragment of LC3
      is cleaved immediately following synthesis to yield a cytosolic form called LC3
      I. A subpopulation of LC3-I is further converted to an autophagosome-associating
      form, LC3-II. Because yeast Atg8 is conjugated with phosphatidylethanolamine (PE)
      by a ubiquitin-like system, it has been hypothesized that LC3 is modified in a
      similar manner. Here, we show that [(14)C]-ethanolamine was preferentially
      incorporated into LC3-II, suggesting that LC3-II is a PE-conjugated form. LC3-II
      can be a substrate of mammalian Atg4B, a homologue of yeast Atg8-PE deconjugase,
      supporting the idea that LC3-II is LC3-PE. Moreover, two other mammalian
      homologues of yeast Atg8, gamma-aminobutyric-acid-type-A-receptor-associated
      protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE16) also
      generate form II, which are recovered in membrane fractions. Generation of the
      form II correlates with autophagosome association of GABARAP and GATE16. These
      results suggest that all mammalian Atg8 homologues receive a common modification
      to associate with autophagosomal membrane as the form II.

PMID- 15169838
TI  - Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293
      cells.
AB  - Intracellular Ca(2+) ([Ca(2+)](i)) oscillations seen in interstitial cells of
      Cajal (ICCs) are considered to be the primary pacemaker activity in the gut.
      Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+)
      stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluster preparations
      isolated from mouse ileum. The pacemaker [Ca(2+)](i) oscillations in ICCs are
      preserved in the presence of dihydropyridine Ca(2+) antagonists, which suppress
      Ca(2+) activity in smooth muscle cells. However, applications of drugs affecting
      either ryanodine receptors or inositol 1,4,5-trisphosphate receptors terminated
      [Ca(2+)](i) oscillations at relatively low concentrations. RT-PCR analyses
      revealed a predominant expression of type 3 RyR (RyR3) in isolated c-Kit
      immunopositive cells (ICCs). Furthermore, we demonstrate that pacemaker-like
      global [Ca(2+)](i) oscillation activity is endowed by introducing RyR3 into
      HEK293 cells, which originally express only IP(3)Rs. The reconstituted
      [Ca(2+)](i) oscillations in HEK293 cells possess essentially the same
      pharmacological characteristics as seen in ICCs. The results support the
      functional role of RyR3 in ICCs.

PMID- 15169839
TI  - Snail and E47 repressors of E-cadherin induce distinct invasive and angiogenic
      properties in vivo.
AB  - The transcription factors Snail and E47 are direct repressors of E-cadherin, with
      both inducing a full epithelial-mesenchymal transition and invasive behaviour in
      vitro when expressed in the prototypic epithelial MDCK cell line. The role of
      these repressors in the invasive process and in other tumorigenic properties is,
      nevertheless, still poorly understood. However, organotypic cultures and in vivo
      transplantation assays indicate that cells expressing MDCK-Snail and MDCK-E47
      exhibit significant differences. MDCK-Snail cells have a higher infiltrative
      potential than MDCK-E47 cells. Interestingly, both cell types induce angiogenesis
      of the host stromal tissue in transplantation assays, but this property is
      greatly enhanced in transplants of MDCK-E47 cells. Xenografted tumours induced in
      nude mice also show signs of strong angiogenic potential, again markedly
      increased in tumours induced by MDCK-E47 which exhibit a higher vessel density
      and proliferation rate than those induced by MDCK-Snail cells. These results
      suggest differential roles for Snail and E47 E-cadherin repressors in tumour
      progression where Snail is implicated in promoting the initial invasion and E47
      plays an active role in tumour cell growth by promoting angiogenesis.

PMID- 15169840
TI  - Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through
      PKCalpha independently of Rho-like GTPases.
AB  - The activated leukocyte cell adhesion molecule (ALCAM) is dynamically regulated
      by the actin cytoskeleton. In this study we explored the molecular mechanisms and
      signaling pathways underlying the cytoskeletal restraints of this homotypic
      adhesion molecule. We observed that ALCAM-mediated adhesion induced by
      cytoskeleton-disrupting agents is accompanied by activation of the small GTPases
      RhoA, Rac1 and Cdc42. Interestingly, unlike adhesion mediated by integrins or
      cadherins, ALCAM-mediated adhesion appears to be independent of Rho-like GTPase
      activity. By contrast, we demonstrated that protein kinase C (PKC) plays a major
      role in ALCAM-mediated adhesion. PKC inhibition by chelerythrine chloride and
      myristoylated PKC pseudosubstrate, as well as PKC downregulation by PMA strongly
      reduce cytoskeleton-dependent ALCAM-mediated adhesion. Since serine and threonine
      residues are dispensable for ALCAM-mediated adhesion and ALCAM is not
      phosphorylated, we can rule out that ALCAM itself is a direct PKC substrate. We
      conclude that PKCalpha plays a dominant role in cytoskeleton-dependent avidity
      modulation of ALCAM.

PMID- 15169841
TI  - Targeted expression of a dominant-negative N-cadherin in vivo delays peak bone
      mass and increases adipogenesis.
AB  - We studied the function of osteoblast cadherins in vivo by transgenic expression
      of a truncated N-cadherin with dominant-negative action, driven by an osteoblast
      specific promoter (OG2-NcadDeltaC). During the first 3 months of life, bone
      mineral density was reduced, whereas percent body fat was increased in transgenic
      animals compared with wild-type littermates, with associated decreased bone
      formation rate and osteoblast number, but normal osteoclast number. Osteoblast
      differentiation was delayed in calvaria cells isolated from transgenic mice.
      Likewise, the number of osteoblast precursors in bone marrow stromal cells from
      OG2-NcadDeltaC mice was decreased compared with wild-type cultures, whereas the
      number of adipogenic precursors was increased. In vitro, a transcriptionally
      active beta-catenin mutant reversed the delay in osteoblast differentiation and
      the exuberant adipogenesis. Thus, in vivo disruption of cadherin function hinders
      osteoblast differentiation and favors, indirectly, bone marrow progenitor cell
      commitment to the alternative adipogenic lineage via interference with beta
      catenin signaling. This results in decreased bone formation, delayed acquisition
      of peak bone mass and increased body fat.

PMID- 15169842
TI  - How shunting inhibition affects the discharge of lumbar motoneurones: a dynamic
      clamp study in anaesthetized cats.
AB  - In the present work, dynamic clamp was used to inject a current that mimicked
      tonic synaptic activity in the soma of cat lumbar motoneurones with a
      microelectrode. The reversal potential of this current could be set at the
      resting potential so as to prevent membrane depolarization or hyperpolarization.
      The only effect of the dynamic clamp was then to elicit a constant and calibrated
      increase of the motoneurone input conductance. The effect of the resulting shunt
      was investigated on repetitive discharges elicited by current pulses. Shunting
      inhibition reduced very substantially the firing frequency in the primary range
      without changing the slope of the current-frequency curves. The shift of the I-f
      curve was proportional to the conductance increase imposed by the dynamic clamp
      and depended on an intrinsic property of the motoneurone that we called the shunt
      potential. The shunt potential ranged between 11 and 37 mV above the resting
      potential, indicating that the sensitivity of motoneurones to shunting inhibition
      was quite variable. The shunt potential was always near or above the action
      potential voltage threshold. A theoretical model allowed us to interpret these
      experimental results. The shunt potential was shown to be a weighted time average
      of membrane voltage. The weighting factor is the phase response function of the
      neurone that peaks at the end of the interspike interval. The shunt potential
      indicates whether mixed synaptic inputs have an excitatory or inhibitory effect
      on the ongoing discharge of the motoneurone.

PMID- 15169843
TI  - The possum sphincter of Oddi pumps or resists flow depending on common bile duct
      pressure: a multilumen manometry study.
AB  - The sphincter of Oddi (SO) regulates trans-sphincteric flow (TSF) by acting
      primarily as a pump or as a resistor in specific species. We used the Australian
      possum SO, which functions similarly to the human SO, to characterize SO motility
      responses to different common bile duct (CBD) and duodenal pressures. Possum CBD,
      SO and attached duodenum (n= 18) was mounted in an organ bath. External
      reservoirs were used to impose CBD (0-17 mmHg) and duodenal (0, 4, 7 mmHg)
      pressure. Spontaneous SO activity was recorded using four-lumen pico-manometry
      and TSF was measured gravimetrically. Temporal analysis of manometric and TSF
      recordings identified three functionally distinct biliary-SO regions, the
      proximal-SO (juxta-CBD), body-SO and papilla-SO. At CBD pressures < 3 mmHg the
      motor activity of these regions was coordinated to pump fluid. Proximal-SO
      contractions isolated fluid within the body-SO. Peristaltic contraction through
      the body-SO pumped this fluid through the papilla-SO (17-27 microl contraction),
      which opened to facilitate flow. CBD pressure > 3.5 mmHg resulted in progressive
      changes in TSF to predominantly passive 'resistor'-type flow, occurring during
      proximal-SO-body-SO quiescence, when CBD pressure exceeded the pressure at the
      papilla-SO. Progression from pump to resistor function commenced when CBD
      pressure was 2-4 mmHg greater than duodenal pressure. These results imply that
      TSF is dependent on the CBD-duodenal pressure difference. The papilla-SO is
      pivotal to TSF, relaxing during proximal-SO-body-SO pumping and closing during
      proximal-SO-body-SO quiescence. The pump function promotes TSF at low CBD
      pressure and prevents bile stasis. At higher CBD pressure, the papilla-SO permits
      TSF along a pressure gradient, thereby maintaining a low pressure within the
      biliary tract.

PMID- 15169844
TI  - The role of oxygen in determining phosphocreatine onset kinetics in exercising
      humans.
AB  - 31P-magnetic resonance spectroscopy was used to study phosphocreatine (PCr) onset
      kinetics in exercising human gastrocnemius muscle under varied fractions of
      inspired O(2) (F(IO(2))). Five male subjects performed three identical work bouts
      (5 min duration; order randomised) at a submaximal workload while breathing 0.1,
      0.21 or 1.0 F(IO(2)). Either a single or double exponential model was fitted to
      the PCr kinetics. The phase I tau (0.1, 38.6 +/- 7.5; 0.21, 34.5 +/- 7.9; 1.0,
      38.6 +/- 9.2 s) and amplitude, A(1) (0.1, 0.34 +/- 0.03; 0.21, 0.28 +/- 0.05;
      1.0, 0.28 +/- 0.03,% fall in PCr) were invariant (both P > 0.05) across F(IO(2))
      trials. The initial rate of change in PCr hydrolysis at exercise onset,
      calculated as A(1)/tau(1) (%PCr reduction s(-1)), was the same across F(IO(2))
      trials. A PCr slow component (phase II) was present at an F(IO(2)) of 0.1 and
      0.21; however, breathing 1.0 F(IO(2)) ablated the slow component. The onset of
      the slow component resulted in a greater (P< or = 0.05) overall percentage fall
      in PCr (both phase I and II) as F(IO(2)) decreased (0.43 +/- 0.05, 0.34 +/- 0.05,
      0.28 +/- 0.03) for 0.1, 0.21 and 1.0 F(IO(2)), respectively. These data
      demonstrate that altering F(IO(2)) does not affect the initial phase I PCr onset
      kinetics, which supports the notion that O(2) driving pressure does not limit PCr
      kinetics at the onset of submaximal exercise. Thus, these data imply that the
      manner in which microvascular and intracellular P(O(2)) regulates PCr hydrolysis
      in exercising muscle is not due to the initial kinetic fall in PCr at exercise
      onset.

PMID- 15169845
TI  - AMPA-receptor activation regulates the diffusion of a membrane marker in parallel
      with dendritic spine motility in the mouse hippocampus.
AB  - Dendritic spines are the site of most excitatory connections in the hippocampus.
      We have investigated the diffusibility of a membrane-bound green fluorescent
      protein (mGFP) within the inner leaflet of the plasma membrane using Fluorescence
      Recovery After Photobleaching. In dendritic spines the diffusion of mGFP was
      significantly retarded relative to the dendritic shaft. In parallel, we have
      assessed the motility of dendritic spines, and found an inverse correlation
      between spine motility and the rate of diffusion of mGFP. We then tested the
      influence of glutamate receptor activation or blockade, and the involvement of
      the actin cytoskeleton (using latrunculin A) on spine motility and mGFP
      diffusion. These results show that glutamate receptors regulate the mobility of
      molecules in the inner leaflet of the plasma membrane through an action upon the
      actin cytoskeleton, suggesting a novel mechanism for the regulation of
      postsynaptic receptor density and composition.

PMID- 15169846
TI  - Functional interaction between extracellular sodium, potassium and inactivation
      gating in HERG channels.
AB  - We have studied the interaction between extracellular K(+) (K(+)(o)) and
      extracellular Na(+) (Na(+)(o)) in human ether-a-go-go related gene (HERG)-encoded
      K(+) channels expressed in Chinese hamster ovary (CHO-K1) cells, using the whole
      cell voltage clamp technique. Prior studies indicate that Na(+)(o) potently
      inhibits HERG current (IC(50) 3 mm) by binding to an outer pore site, and also
      speeds recovery from inactivation. In this study, we sought to explore the
      relationship between the Na(+)(o) effect on recovery and Na(+)(o) inhibition of
      HERG current, and to determine whether inactivation gating plays a critical role
      in Na(+)(o) inhibition of HERG current. Na(+)(o) concentration-response
      relationships for current inhibition and speeding of recovery were different,
      with Na(+)(o) less potent at speeding recovery. Na(+)(o) inhibition of HERG
      current was relieved by physiological [K(+)](o), while Na(+)(o) speeded recovery
      from inactivation similarly in the absence or presence of physiological
      [K(+)](o). To examine the link between Na(+)(o) block and inactivation using an
      independent approach, we studied hyperpolarization-activated currents uncoupled
      from inactivation in the S4-S5 linker mutant D540K. Depolarization-activated
      D540K currents were inhibited by Na(+)(o), while hyperpolarization-activated
      currents were augmented by Na(+)(o). This result reveals a direct link between
      Na(+)(o) inhibition and a depolarization-induced conformational change, most
      likely inactivation. We attempted to simulate the disparate concentration
      response relationships for the two effects of Na(+)(o) using a kinetic model that
      included Na(+)(o) site(s) affected by permeation and gating. While a model with
      only a single dynamic Na(+)(o) site was inadequate, a model with two distinct
      Na(+)(o) sites was sufficient to reproduce the data.

PMID- 15169847
TI  - Isoflurane depresses glutamate release by reducing neuronal excitability at the
      Drosophila neuromuscular junction.
AB  - The mechanisms through which volatile general anaesthetics exert their
      behavioural effects remain unclear. The accessibility of the Drosophila larval
      neuromuscular junction to genetic and neurophysiological analysis has made it an
      attractive model system for identification of anaesthetic targets. This study
      provides a mechanistic basis for the genetic analysis of anaesthetic action, by
      analysing the neurophysiological effects of the volatile anaesthetic isoflurane
      on axonal and synaptic function in the Drosophila larva. The most robust effect
      of isoflurane was a reversible decrease in the amplitude and area of
      glutamatergic excitatory junctional currents (EJCs) evoked at the neuromuscular
      junction. Isoflurane did not affect postsynaptic glutamate receptor function
      detectably, in that the amplitudes, areas and decay times of spontaneous
      miniature EJCs were unchanged at any concentration. Therefore, decreased EJC
      amplitude resulted from reduction of neurotransmitter release. Reduced
      neurotransmitter release was associated with decreased presynaptic excitability,
      measured as increased delay to EJC onset and reduced axonal conduction velocity.
      EJC amplitude was rescued to control levels by direct electrotonic stimulation of
      the synapse in the presence of tetrodotoxin, indicating that isoflurane inhibits
      neurotransmitter release by reducing presynaptic excitability. In addition,
      isoflurane reduced release probability, measured as increased paired-pulse
      facilitation. The EC(50) for suppression of larval locomotion was similar to that
      for reduction of transmitter release, indicating that the axonal and synaptic
      effects were occurring in a behaviourally relevant range. These results provide a
      cellular context for ongoing genetic and neurophysiological analyses of volatile
      anaesthetic action in Drosophila, and suggest candidate anaesthetic target
      molecules.

PMID- 15169851
TI  - Pavlovian conditioning of Hermissenda: current cellular, molecular, and circuit
      perspectives.
AB  - The less-complex central nervous system of many invertebrates make them
      attractive for not only the molecular analysis of the associative learning and
      memory, but also in determining how neural circuits are modified by learning to
      generate changes in behavior. The nudibranch mollusk Hermissenda crassicornis is
      a preparation that has contributed to an understanding of cellular and molecular
      mechanisms of Pavlovian conditioning. Identified neurons in the conditioned
      stimulus (CS) pathway have been studied in detail using biophysical, biochemical,
      and molecular techniques. These studies have resulted in the identification and
      characterization of specific membrane conductances contributing to enhanced
      excitability and synaptic facilitation in the CS pathway of conditioned animals.
      Second-messenger systems activated by the CS and US have been examined, and
      proteins that are regulated by one-trial and multi-trial Pavlovian conditioning
      have been identified in the CS pathway. The recent progress that has been made in
      the identification of the neural circuitry supporting the unconditioned response
      (UR) and conditioned response (CR) now provides for the opportunity to understand
      how Pavlovian conditioning is expressed in behavior.

PMID- 15169848
TI  - Supplementation with vitamins C and E inhibits the release of interleukin-6 from
      contracting human skeletal muscle.
AB  - Contracting human skeletal muscle is a major contributor to the exercise-induced
      increase of plasma interleukin-6 (IL-6). Although antioxidants have been shown to
      attenuate the exercise-induced increase of plasma IL-6, it is unknown whether
      antioxidants inhibit transcription, translation or translocation of IL-6 within
      contracting human skeletal muscle. Using a single-blind placebo-controlled design
      with randomization, young healthy men received an oral supplementation with
      either a combination of ascorbic acid (500 mg day(-1)) and RRR-alpha-tocopherol
      (400 i.u. day(-1)) (Treatment, n= 7), or placebo (Control, n= 7). After 28 days
      of supplementation, the subjects performed 3 h of dynamic two-legged knee
      extensor exercise at 50% of their individual maximal power output. Muscle
      biopsies from vastus lateralis were obtained at rest (0 h), immediately post
      exercise (3 h) and after 3 h of recovery (6 h). Leg blood flow was measured using
      Doppler ultrasonography. Plasma IL-6 concentration was measured in blood sampled
      from the femoral artery and vein. The net release of IL-6 was calculated using
      Fick's principle. Plasma vitamin C and E concentrations were elevated in
      Treatment compared to Control. Plasma 8-iso-prostaglandin F(2alpha), a marker of
      lipid peroxidation, increased in response to exercise in Control, but not in
      Treatment. In both Control and Treatment, skeletal muscle IL-6 mRNA and protein
      levels increased between 0 and 3 h. In contrast, the net release of IL-6 from the
      leg, which increased during exercise with a peak at 3.5 h in Control, was
      completely blunted during exercise in Treatment. The arterial plasma IL-6
      concentration from 3 to 4 h, when the arterial IL-6 levels peaked in both groups,
      was approximately 50% lower in the Treatment group compared to Control (Treatment
      versus Control: 7.9 pg ml(-1), 95% confidence interval (CI) 6.0-10.7 pg ml(-1),
      versus 19.7 pg ml(-1), CI 13.8-29.4 pg ml(-1), at 3.5 h, P < 0.05 between
      groups). Moreover, plasma interleukin-1 receptor antagonist (IL-1ra), C-reactive
      protein and cortisol levels all increased after the exercise in Control, but not
      in Treatment. In conclusion, our results show that supplementation with vitamins
      C and E attenuated the systemic IL-6 response to exercise primarily via
      inhibition of the IL-6 protein release from the contracting skeletal muscle per
      se.

PMID- 15169850
TI  - Bradykinin decreases K(+) and increases Cl(-) conductances in vagal afferent
      neurones of the guinea pig.
AB  - Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary
      afferent neurones. The nature of the ionic channels underlying the excitatory
      actions of BK is still incompletely understood. Using whole-cell patch-clamp
      recording from acutely dissociated nodose ganglion neurones (NGNs) we have
      examined the ionic mechanism responsible for BK's excitatory effect. Bath-applied
      BK (0.1 microM) depolarized the membrane potential (29 +/- 3.1 mV, n= 7), evoked
      action potentials, and induced an inward ionic current (I(BK)) with two
      distinctive membrane conductances (g(m)). Initially, g(m) decreased; the ionic
      current associated with this g(m) had a reversal potential (E(rev)) value of -87
      +/- 1.1 mV (n= 26), a value close to E(K) (-89 mV). Subsequently, g(m) increased;
      the ionic current associated with this g(m) had an estimated E(rev) of 49 +/- 4.3
      mV (n= 23). When the second component was isolated from the first component, by
      replacing [K(+)](o) with Cs(+), E(rev) was 20 +/- 4.7 mV (n= 10). Replacing
      external NaCl with NMDG-Cl or choline-Cl, or reducing [Ca(2+)](o) did not
      significantly diminish I(BK). After replacing external NaCl with sodium
      isethionate, E(rev) for the second component shifted to 56 +/- 8.8 mV (n= 4), a
      value close to the E(Cl) (66 mV). The second component was inhibited by
      intracellular BAPTA or by bath application of niflumic acid (100 microM), a
      Ca(2+)-activated Cl(-) channel blocker. These results suggest that the first and
      second components of I(BK) are produced by a decrease in K(+) conductance and an
      increase in Ca(2+)-activated Cl(-) conductance, respectively. The BK-evoked Cl(-)
      conductance in NGNs may be the first demonstration of an inflammatory mediator
      exciting primary afferents via an anion channel.

PMID- 15169849
TI  - Knockout of the ASIC2 channel in mice does not impair cutaneous mechanosensation,
      visceral mechanonociception and hearing.
AB  - Mechanosensitive cation channels are thought to be crucial for different aspects
      of mechanoperception, such as hearing and touch sensation. In the nematode C.
      elegans, the degenerins MEC-4 and MEC-10 are involved in mechanosensation and
      were proposed to form mechanosensitive cation channels. Mammalian degenerin
      homologues, the H(+)-gated ASIC channels, are expressed in sensory neurones and
      are therefore interesting candidates for mammalian mechanosensors. We
      investigated the effect of an ASIC2 gene knockout in mice on hearing and on
      cutaneous mechanosensation and visceral mechanonociception. However, our data do
      not support a role of ASIC2 in those facets of mechanoperception.

PMID- 15169852
TI  - A cell-permeable phospholipase Cgamma1-binding peptide transduces neurons and
      impairs long-term spatial memory.
AB  - Growth factor-mediated signaling has emerged as an essential component of memory
      formation. In this study, we used a phospholipase C gamma 1 (PLCgamma1) binding,
      cell-penetrating peptide to sequester PLCgamma1 away from its target, the
      phosphotyrosine residues within the activated growth factor receptor. Peptides
      appear to transduce neurons but not astrocytes or oligodendrocytes. The presence
      of the peptides in the hippocampus during training in the Morris water maze
      significantly impaired long-term memory, but not memory acquisition. These
      results, along with previous studies on extracellular signal-regulated kinase
      (ERK) and phosphoinositide-3 kinase (PI3K), implicate all three key growth factor
      receptor-activated intracellular signaling pathways in memory storage.

PMID- 15169853
TI  - Neurobiological and endocrine correlates of individual differences in spatial
      learning ability.
AB  - The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated
      in activity-dependent synaptic remodeling and memory formation. Here, we
      questioned whether training-induced modulation of PSA-NCAM expression might be
      related to individual differences in spatial learning abilities. At 12 h
      posttraining, immunohistochemical analyses revealed a learning-induced up
      regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the
      spatial learning abilities displayed by rats during training. Specifically, a
      positive correlation was found between latency to find the platform and
      subsequent activated PSA levels, indicating that greater induction of
      polysialylation was observed in rats with the slower acquisition curve. At
      posttraining times when no learning-associated activation of PSA was observed, no
      such correlation was found. Further experiments revealed that performance in the
      massed water maze training is related to a pattern of spatial learning and memory
      abilities, and to learning-related glucocorticoid responsiveness. Taken together,
      our findings suggest that the learning-related neural circuits of fast learners
      are better suited to solving the water maze task than those of slow learners, the
      latter relying more on structural reorganization to form memory, rather than the
      relatively economic mechanism of altering synaptic efficacy that is likely used
      by the former.

PMID- 15169855
TI  - Sex-related hemispheric lateralization of amygdala function in emotionally
      influenced memory: an FMRI investigation.
AB  - The amygdala appears necessary for enhanced long-term memory associated with
      emotionally arousing events. Recent brain imaging investigations support this
      view and indicate a sex-related hemispheric lateralization exists in the amygdala
      relationship to memory for emotional material. This study confirms and further
      explores this finding. Healthy men and women underwent functional Magnetic
      Resonance Imaging (fMRI) while viewing a series of standardized slides that were
      rated by the subjects as ranging from emotionally neutral to highly arousing. Two
      weeks later, memory for the slides was assessed in an incidental recognition
      test. The results demonstrate a significantly stronger relationship in men than
      in women between activity of the right hemisphere amygdala and memory for those
      slides judged as arousing, and a significantly stronger relationship in women
      than in men between activity of the left hemisphere amygdala and memory for
      arousing slides. An ANOVA confirmed a significant interaction between sex and
      hemisphere regarding amygdala function in memory. These results provide the
      strongest evidence to date of a sex-related hemispheric lateralization of
      amygdala function in memory for emotional material. Furthermore, they underscore
      the view that investigations of neural mechanisms underlying emotionally
      influenced memory must anticipate, and begin to account for, the apparently
      substantial influence of sex.

PMID- 15169857
TI  - Learning and memory deficits upon TAU accumulation in Drosophila mushroom body
      neurons.
AB  - Mutations in the neuronal-specific microtubule-binding protein TAU are associated
      with several dementias and neurodegenerative diseases. However, the effects of
      elevated TAU accumulation on behavioral plasticity are unknown. We report that
      directed expression of wild-type vertebrate and Drosophila TAU in adult mushroom
      body neurons, centers for olfactory learning and memory in Drosophila, strongly
      compromised associative olfactory learning and memory, but olfactory conditioning
      relevant osmotactic and mechanosensory responses remained intact. In addition,
      TAU accumulation in mushroom body neurons did not result in detectable
      neurodegeneration or premature death. Therefore, TAU-mediated structural or
      functional perturbation of the microtubular cytoskeleton in mushroom body neurons
      is likely causal of the behavioral deficit. These results indicate that
      behavioral plasticity decrements may be the earliest detectable manifestations of
      tauopathies.

PMID- 15169856
TI  - Temporal characteristics of the predictive synchronous firing modeled by spike
      timing-dependent plasticity.
AB  - When a sensory cue was repeatedly followed by a behavioral event with fixed
      delays, pairs of premotor and primary motor neurons showed significant increases
      of coincident spikes at times a monkey was expecting the event. These results
      provided evidence that neuronal firing synchrony has predictive power. To
      elucidate the underlying mechanism, here we argue some nontrivial characteristics
      of the predictive synchronous firing developed by spike-timing-dependent
      plasticity in a paradigm similar to classical conditioning. We find that the
      computationally developed synchrony shows the modulations of temporal precision,
      which are quite similar to those observed experimentally. Thus, our model
      suggests that the important characteristics of predictive synchronous firing,
      which were previously attributed to an animal's higher cognitive function, can
      emerge from a synaptic-level mechanism.

PMID- 15169858
TI  - Context-dependent olfactory learning in an insect.
AB  - We studied the capability of the cricket Gryllus bimaculatus to select one of a
      pair of odors and to avoid the other in one context and to do the opposite in
      another context. One group of crickets was trained to associate one of a pair of
      odors (conditioned stimulus, CS1) with water reward (appetitive unconditioned
      stimulus, US+) and another odor (CS2) with saline solution (aversive US, US-)
      under illumination and to associate CS1 with US- and CS2 with US+ in the dark.
      Another group of crickets received training of the opposite stimulus arrangement.
      At 1 d after the training for 3 d, the former group significantly preferred CS1
      over CS2 under illumination but preferred CS2 over CS1 in the dark, and the
      latter group exhibited the opposite odor preference. The results of control
      experiments showed that the background light condition had no significant effects
      on memory formation or retrieval unless it was explicitly associated with US
      during training. Thus, the visual context affected learning performance only when
      crickets were requested to use it to disambiguate the meaning of CSs and to
      predict USs.

PMID- 15169854
TI  - Altered hippocampal transcript profile accompanies an age-related spatial memory
      deficit in mice.
AB  - We have carried out a global survey of age-related changes in mRNA levels in the
      C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene
      expression profile between 2-month-old young mice and 15-month-old middle-aged
      mice correlated with an age-related cognitive deficit in hippocampal-based
      explicit memory formation. Middle-aged mice displayed a mild but specific deficit
      in spatial memory in the Morris water maze. By using Affymetrix GeneChip
      microarrays, we found a distinct pattern of age-related change, consisting mostly
      of gene overexpression in the middle-aged mice, suggesting that the induction of
      negative regulators in the middle-aged hippocampus could be involved in
      impairment of learning. Interestingly, we report changes in transcript levels for
      genes that could affect synaptic plasticity. Those changes could be involved in
      the memory deficits we observed in the 15-month-old mice. In agreement with
      previous reports, we also found altered expression in genes related to
      inflammation, protein processing, and oxidative stress.

PMID- 15169859
TI  - Associative mechanosensory conditioning of the proboscis extension reflex in
      honeybees.
AB  - The present work introduces a form of associative mechanosensory conditioning of
      the proboscis extension reflex (PER) in honeybees. In our paradigm, harnessed
      honeybees learn the elemental association between mechanosensory, antennal
      stimulation and a reward of sucrose solution delivered to the proboscis.
      Thereafter, bees extend their proboscis to the antennal mechanosensory
      stimulation alone. We show that bees can learn such an association in a side
      specific manner, that is, they learn the association on the antennal side that
      was rewarded and not on the side that was not rewarded. Responding produced by
      the paired training does likely contain a substantial Pavlovian component.
      Responding is only elicited by mechanosensory stimulation and not by spurious
      cues such as olfactory, visual, and contextual ones. The interstimulus interval
      (ISI) affects one-trial mechanosensory learning: a bell-shaped curve with a
      maximum of responding approximately 4 sec ISI was obtained. Mechanosensory memory
      is still operative 24 h after conditioning. Apart from absolute conditioning in
      which mechanosensory stimulation of one antenna is paired with sucrose,
      differential, side-specific, mechanosensory conditioning using two mechanosensory
      stimulations, one rewarded and the other not, is also possible. This paradigm
      constitutes, therefore, a new standard procedure for further learning studies in
      honeybees.

PMID- 15169860
TI  - Activity of cGMP-dependent protein kinase (PKG) affects sucrose responsiveness
      and habituation in Drosophila melanogaster.
AB  - The cGMP-dependent protein kinase (PKG) has many cellular functions in
      vertebrates and insects that affect complex behaviors such as locomotion and
      foraging. The foraging (for) gene encodes a PKG in Drosophila melanogaster. Here,
      we demonstrate a function for the for gene in sensory responsiveness and
      nonassociative learning. Larvae of the natural variant sitter (for(s)) show less
      locomotor activity during feeding and have a lower PKG activity than rover
      (for(R)) larvae. We used rover and sitter adult flies to test whether PKG
      activity affects (1) responsiveness to sucrose stimuli applied to the front
      tarsi, and (2) habituation of proboscis extension after repeated sucrose
      stimulation. To determine whether the differences observed resulted from
      variation in the for gene, we also tested for(s2), a sitter mutant produced on a
      rover genetic background. We found that rovers (for(R)) were more responsive to
      sucrose than sitters (for(s) and for(s2)) at 1-, 2-, and 3-wk old. This was true
      for both sexes. Differences in sucrose responsiveness between rovers and sitters
      were greater after 2 h of food deprivation than after 24 h. Of flies with similar
      sucrose responsiveness, for(R) rovers showed less habituation and generalization
      of habituation than for(s) and for(s2) sitters. These results show that the PKG
      encoded by for independently affects sensory responsiveness and habituation in
      Drosophila melanogaster.

PMID- 15169861
TI  - Enhancement of inhibitory avoidance and conditioned taste aversion memory with
      insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala.
AB  - There is considerable evidence that in rats, the insular cortex (IC) and amygdala
      are involved in the learning and memory of aversively motivated tasks. The
      present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and
      oxotremorine, a muscarinic agonist, infused into the IC after inhibitory
      avoidance (IA) training and during the acquisition/consolidation of conditioned
      taste aversion (CTA). Posttraining infusion into the IC of 0.3 microg
      oxotremorine and 1.25 microg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br
      cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments
      also examined whether noradrenergic activity in the basolateral amygdala (BLA) is
      critical in enabling the enhancement of CTA and IA memory induced by drug
      infusions administered into the IC. For both CTA and IA, ipsilateral infusions of
      beta-adrenergic antagonist propranolol administered into the BLA blocked the
      retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC.
      These results indicate that the IC is involved in the consolidation of memory for
      both IA and CTA, and this effect requires intact noradrenergic activity into the
      BLA. These findings provide additional evidence that the BLA interacts with other
      brain regions, including sensory cortex, in modulating memory consolidation.

PMID- 15169863
TI  - A test of transitive inferences in free-flying honeybees: unsuccessful
      performance due to memory constraints.
AB  - We asked whether honeybees, Apis mellifera, could solve a transitive inference
      problem. Individual free-flying bees were conditioned with four overlapping
      premise pairs of five visual patterns in a multiple discrimination task (A+ vs. B
      , B+ vs. C-, C+ vs. D-, D+ vs. E-, where + and - indicate sucrose reward or
      absence of it, respectively). They were then tested with the nonadjacent pairs A
      vs. E and B vs. D. Preference of B to D is consistent with the use of the
      implicit hierarchy A > B > C > D > E. Equal choice of B and D supports choice
      based on the associative strength of the stimuli. The bees' choice was determined
      by their memory constraints: experience with the last premise pair (D+ vs. E-)
      predominated. In the tests, bees preferred A to E and chose equally B and D. An
      analysis of the performance in terms of a reward/penalty ratio showed that B had
      a higher associative strength than D. Thus, bees do not establish transitive
      inferences but, rather, guide their choices by the joint action of a recency
      effect and the associative strength of the stimuli. The former supports choice of
      D, whereas the latter supports choice of B, thus determining equal choice of B
      and D in the tests.

PMID- 15169862
TI  - Selective modulation of some forms of schaffer collateral-CA1 synaptic plasticity
      in mice with a disruption of the CPEB-1 gene.
AB  - CPEB-1 is a sequence-specific RNA binding protein that stimulates the
      polyadenylation-induced translation of mRNAs containing the cytoplasmic
      polyadenylation element (CPE). Although CPEB-1 was identified originally in
      Xenopus oocytes, it has also been found at postsynaptic sites of hippocampal
      neurons where, in response to N-methyl-D-aspartate receptor activation, it is
      thought to induce the polyadenylation and translation of alphaCaMKII and perhaps
      other CPE-containing mRNAs. Because some forms of synaptic modification appear to
      be influenced by local (synaptic) protein synthesis, we examined long-term
      potentiation (LTP) in CPEB-1 knockout mice. Although the basal synaptic
      transmission of Schaffer collateral-CA1 neurons was not affected in the knockout
      mice, we found that there was a modest deficit in LTP evoked by a single train of
      100 Hz stimulation, but a greater deficit in LTP evoked by one train of theta
      burst stimulation. In contrast, LTP evoked by either four trains of 100 Hz
      stimulation or five trains of theta-burst stimulation were not or were only
      modestly affected, respectively. The deficit in LTP evoked by single stimulation
      in knockout mice appeared several minutes after tetanic stimulation. Long-term
      depression (LTD) evoked by 1 Hz stimulation was moderately facilitated; however,
      a stronger and more enduring form of LTD induced by paired-pulse 1 Hz stimulation
      was unaffected. These data suggest that CPEB-1 contributes in the translational
      control of mRNAs that is critical only for some selected forms of LTP and LTD.

PMID- 15169866
TI  - Task requirements influence sensory integration during grasping in humans.
AB  - The sensorimotor transformations necessary for generating appropriate motor
      commands depend on both current and previously acquired sensory information. To
      investigate the relative impact (or weighting) of visual and haptic information
      about object size during grasping movements, we let normal subjects perform a
      task in which, unbeknownst to the subjects, the object seen (visual object) and
      the object grasped (haptic object) were never the same physically. When the
      haptic object abruptly became larger or smaller than the visual object, subjects
      in the following trials automatically adapted their maximum grip aperture when
      reaching for the object. This adaptation was not dependent on conscious
      processes. We analyzed how visual and haptic information were weighted during the
      course of sensorimotor adaptation. The adaptation process was quicker and relied
      more on haptic information when the haptic objects increased in size than when
      they decreased in size. As such, sensory weighting seemed to be molded to avoid
      prehension error. We conclude from these results that the impact of a specific
      source of sensory information on the sensorimotor transformation is regulated to
      satisfy task requirements.

PMID- 15169865
TI  - Learning of sensory sequences in cerebellar patients.
AB  - A possible role of the cerebellum in detecting and recognizing event sequences
      has been proposed. The present study sought to determine whether patients with
      cerebellar lesions are impaired in the acquisition and discrimination of
      sequences of sensory stimuli of different modalities. A group of 26 cerebellar
      patients and 26 controls matched for age, sex, handedness, musicality, and level
      of education were tested. Auditory and visual sensory sequences were presented
      out of different sensory pattern categories (tones with different acoustic
      frequencies and durations, visual stimuli with different spatial locations and
      colors, sequential vision of irregular shapes) and different ranges of inter-cue
      time intervals (fast and slow). Motor requirements were small, with vocal
      responses and no time restrictions. Perception of visual and acoustic stimuli was
      generally preserved in patients and controls. The number of errors was
      significantly higher in the faster tempo of sequence presentation in learning of
      sequences of tones of different frequencies and in learning of sequences of
      visual stimuli of different spatial locations and different colors. No difference
      in tempo between the groups was shown. The total number of errors between the two
      groups was identical in the sequence conditions. No major disturbances in
      acquisition or discrimination of various sensory sequences were observed in the
      group of cerebellar patients. Sequence learning may be impaired only in tasks
      with significant motor demands.

PMID- 15169864
TI  - Search strategies used by APP transgenic mice during navigation in the Morris
      water maze.
AB  - TgCRND8 mice represent a transgenic mouse model of Alzheimer's disease, with
      onset of cognitive impairment and increasing amyloid-beta plaques in their brains
      at 12 weeks of age. In this study, the spatial memory in 25- to 30-week-old
      TgCRND8 mice was analyzed in two reference and one working memory Morris water
      maze (MWM) tests. In reference memory tests, the mice were trained to escape to a
      hidden platform, which in one version of the test was marked by a visual cue. In
      the working memory test, the hidden platform was moved daily to different
      locations. The TgCRND8 mice were impaired in reference memory when trained in a
      hidden platform test. However, the mice developed spatial memory comparable to
      non-Tg littermates in a cued reference memory test. The mice showed also an
      impairment in spatial working memory. Analysis of search paths revealed that in
      contrast to non-Tg littermates, TgCRND8 mice did not use spatial strategies
      during their navigation. Instead, they learned to locate an escape platform using
      a nonspatial, chaining strategy. The study showed that (1) the impairment in the
      reference memory of TgCRND8 mice was reduced when a hidden platform was cued, and
      that (2) both working and reference memory systems of TgCRND8 mice, but not (3)
      the plasticity of choice between search strategies, are compromised by the
      transgene-induced pathology.

PMID- 15169867
TI  - Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C1
      carrier induces pseudohyphal growth.
AB  - Tetrahydrofolate (vitamin B9) and its folate derivatives are essential cofactors
      in one-carbon (C1) transfer reactions and absolutely required for the synthesis
      of a variety of different compounds including methionine and purines. Most
      plants, microbial eukaryotes, and prokaryotes synthesize folate de novo. We have
      characterized an important enzyme in this pathway, the Saccharomyces cerevisiae
      FOL1 gene. Expression of the budding yeast gene FOL1 in Escherichia coli
      identified the folate biosynthetic enzyme activities dihydroneopterin aldolase
      (DHNA), 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK), and
      dihydropteroate synthase (DHPS). All three enzyme activities were also detected
      in wild-type yeast strains, whereas fol1Delta deletion strains only showed
      background activities, thus demonstrating that Fol1p catalyzes three sequential
      steps of the tetrahydrofolate biosynthetic pathway and thus is the central enzyme
      of this pathway, which starting from GTP consists of seven enzymatic reactions in
      total. Fol1p is exclusively localized to mitochondria as shown by fluorescence
      microscopy and immune electronmicroscopy. FOL1 is an essential gene and the
      nongrowth phenotype of the fol1 deletion leads to a recessive auxotrophy for
      folinic acid (5'-formyltetrahydrofolate). Growth of the fol1Delta deletion strain
      on folinic acid-supplemented rich media induced a dimorphic switch with haploid
      invasive and filamentous pseudohyphal growth in the presence of glucose and
      ammonium, which are known suppressors of filamentous and invasive growth. The
      invasive growth phenotype induced by the depletion of C1 carrier is dependent on
      the transcription factor Ste12p and the flocullin/adhesin Flo11p, whereas the
      filamentation phenotype is independent of Ste12p, Tec1p, Phd1p, and Flo11p,
      suggesting other signaling pathways as well as other adhesion proteins.

PMID- 15169868
TI  - Integrative analysis of cell cycle control in budding yeast.
AB  - The adaptive responses of a living cell to internal and external signals are
      controlled by networks of proteins whose interactions are so complex that the
      functional integration of the network cannot be comprehended by intuitive
      reasoning alone. Mathematical modeling, based on biochemical rate equations,
      provides a rigorous and reliable tool for unraveling the complexities of
      molecular regulatory networks. The budding yeast cell cycle is a challenging test
      case for this approach, because the control system is known in exquisite detail
      and its function is constrained by the phenotypic properties of >100 genetically
      engineered strains. We show that a mathematical model built on a consensus
      picture of this control system is largely successful in explaining the phenotypes
      of mutants described so far. A few inconsistencies between the model and
      experiments indicate aspects of the mechanism that require revision. In addition,
      the model allows one to frame and critique hypotheses about how the division
      cycle is regulated in wild-type and mutant cells, to predict the phenotypes of
      new mutant combinations, and to estimate the effective values of biochemical rate
      constants that are difficult to measure directly in vivo.

PMID- 15169870
TI  - Cdc42, Rac1, and Rac2 display distinct patterns of activation during
      phagocytosis.
AB  - The small G proteins Cdc42, Rac1, and Rac2 regulate the rearrangements of actin
      and membrane necessary for Fcgamma receptor-mediated phagocytosis by macrophages.
      Activated, GTP-bound Cdc42, Rac1, and Rac2 bind to the p21-binding domain (PBD)
      of PAK1, and this interaction provided a basis for microscopic methods to
      localize activation of these G proteins inside cells. Fluorescence resonance
      energy transfer-based stoichiometry of fluorescent chimeras of actin, PBD, Cdc42,
      Rac1, and Rac2 was used to quantify G protein activation relative to actin
      movements during phagocytosis of IgG-opsonized erythrocytes. The activation
      dynamics of endogenous G proteins, localized using yellow fluorescent protein
      labeled PBD, was restricted to phagocytic cups, with a prominent spike of
      activation over an actin-poor region at the base of the cup. Refinements of
      fluorescence resonance energy transfer stoichiometry allowed calculation of the
      fractions of activated GTPases in forming phagosomes. Cdc42 activation was
      restricted to the leading margin of the cell, whereas Rac1 was active throughout
      the phagocytic cup. During phagosome closure, activation of Rac1 and Rac2
      increased uniformly and transiently in the actin-poor region of phagosomal
      membrane. These distinct roles for Cdc42, Rac1, and Rac2 in the component
      activities of phagocytosis indicate mechanisms by which their differential
      regulation coordinates rearrangements of actin and membranes.

PMID- 15169869
TI  - Lipid raft-dependent glucagon-like peptide-2 receptor trafficking occurs
      independently of agonist-induced desensitization.
AB  - The intestinotrophic and cytoprotective actions of glucagon-like peptide-2 (GLP
      2) are mediated by the GLP-2 receptor (GLP-2R), a member of the class II glucagon
      secretin G protein-coupled receptor superfamily. Although native GLP-2 exhibits a
      short circulating half-life, long-acting degradation-resistant GLP-2 analogues
      are being evaluated for therapeutic use in human subjects. Accordingly, we
      examined the mechanisms regulating signaling, internalization, and trafficking of
      the GLP-2R to identify determinants of receptor activation and desensitization.
      Heterologous cells expressing the transfected rat or human GLP-2R exhibited a
      rapid, dose-dependent, and prolonged desensitization of the GLP-2-stimulated cAMP
      response and a sustained GLP-2-induced decrease in levels of cell surface
      receptor. Surprisingly, inhibitors of clathrin-dependent endocytosis failed to
      significantly decrease GLP-2R internalization, whereas cholesterol sequestration
      inhibited ligand-induced receptor internalization and potentiated homologous
      desensitization. The hGLP-2R localized to both Triton X-100-soluble and 
      insoluble (lipid raft) cellular fractions and colocalized transiently with the
      lipid raft marker caveolin-1. Although GLP-2R endocytosis was dependent on lipid
      raft integrity, the receptor transiently associated with green fluorescent
      protein tagged-early endosome antigen 1-positive vesicles and inhibitors of
      endosomal acidification attenuated the reappearance of the GLP-2R on the cell
      surface. Our data demonstrate that GLP-2R desensitization and raft-dependent
      trafficking represent distinct and independent cellular mechanisms and provide
      new evidence implicating the importance of a clathrin- and dynamin-independent,
      lipid raft-dependent pathway for homologous G protein-coupled receptor
      internalization.

PMID- 15169871
TI  - Essential role for the myotubularin-related phosphatase Ymr1p and the
      synaptojanin-like phosphatases Sjl2p and Sjl3p in regulation of
      phosphatidylinositol 3-phosphate in yeast.
AB  - The requirement of Vps34p, the sole phosphatidylinositol (PI) 3-kinase in
      Saccharomyces cerevisiae, for protein sorting to the vacuole in yeast has
      exemplified the essential role for phosphoinositides, phosphorylated derivatives
      of PI, in membrane trafficking. To better understand mechanisms that regulate PI
      3-phosphate [PI(3)P]-mediated signaling, the role of the yeast myotubularin
      related PI(3)P phosphatase Ymr1p was investigated. We found that Ymr1p and the
      synaptojanin-like phosphatase Sjl3p function as key regulators of the
      localization and levels of PI(3)P. Our data indicated that the ymr1Delta
      sjl3Delta double mutant aberrantly accumulated PI(3)P and demonstrated a steady
      state redistribution of this lipid that leads to enrichment on the vacuolar
      membrane. This resulted in vacuole protein sorting defects, vacuolar
      fragmentation, and the misregulation of PI(3)P-specific effectors. Triple
      deletion of YMR1, SJL2, and SJL3 was lethal, suggesting an essential requirement
      for phosphatase-mediated PI(3)P regulation. Consistent with this, growth was
      restored to a ymr1Delta sjl2Delta sjl3Delta triple mutant by a PI(3)P-targeted
      Sac1p domain chimera (GFP-Sac1DeltaC-FYVE(EEA1)) that returned PI(3)P to levels
      comparable with wild-type cells. Together, this study demonstrated that Ymr1p, a
      myotubularin phosphatase family member, functions in the control of PI(3)P
      dependent signaling and the maintenance of endosomal system integrity. In
      addition, this work defined an essential overlapping role for lipid phosphatases
      in the regulation of 3' phosphoinositides in yeast.

PMID- 15169872
TI  - Modulation of telomere length dynamics by the subtelomeric region of tetrahymena
      telomeres.
AB  - Tetrahymena telomeres usually consist of approximately 250 base pairs of T(2)G(4)
      repeats, but they can grow to reach a new length set point of up to 900 base
      pairs when kept in log culture at 30 degrees C. We have examined the growth
      profile of individual macronuclear telomeres and have found that the rate and
      extent of telomere growth are affected by the subtelomeric region. When the
      sequence of the rDNA subtelomeric region was altered, we observed a decrease in
      telomere growth regardless of whether the GC content was increased or decreased.
      In both cases, the ordered structure of the subtelomeric chromatin was disrupted,
      but the effect on the telomeric complex was relatively minor. Examination of the
      telomeres from non-rDNA chromosomes showed that each telomere exhibited a unique
      and characteristic growth profile. The subtelomeric regions from individual
      chromosome ends did not share common sequence elements, and they each had a
      different chromatin structure. Thus, telomere growth is likely to be regulated by
      the organization of the subtelomeric chromatin rather than by a specific DNA
      element. Our findings suggest that at each telomere the telomeric complex and
      subtelomeric chromatin cooperate to form a unique higher order chromatin
      structure that controls telomere length.

PMID- 15169874
TI  - Quantitative proteomic and transcriptional analysis of the response to the p38
      mitogen-activated protein kinase inhibitor SB203580 in transformed follicular
      lymphoma cells.
AB  - The p38 mitogen-activated protein kinase (MAPK) is a key mediator of stress,
      extracellular-, growth factor-, and cytokine-induced signaling, and has been
      implicated in the development of cancer. Our previous work showed evidence for
      p38 MAPK activation in a subset of transformed follicular lymphomas (Elenitoba
      Johnson et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 7259). We demonstrated
      that inhibition of p38 MAPK by SB203580 resulted in dose- and time-dependent
      caspase-3-mediated apoptosis. In order to further elucidate the basis of the
      cellular effects of SB203580, we have employed a systems biologic approach
      involving cDNA microarray and quantitative proteomic analysis of transformed
      follicular lymphoma derived-cells (OCI Ly-1) treated with SB203580. Gene
      expression profiling revealed differential expression (>/=1.5-fold) of 374
      genes/ESTs in cells treated for 3 h and 515 genes/ESTs in cells treated for 21 h.
      The majority (52% at 3 h and 91% at 21 h) were down-regulated, including genes
      encoding growth cytokines, transcriptional regulators and cytoskeletal proteins.
      Quantitative proteomic analysis using ICAT-LC-MS/MS identified 277 differentially
      expressed proteins at 3 h and 350 proteins at 21 h of treatment with SB203580,
      the majority of which were also down-regulated. Analysis of functional groups of
      the differentially expressed proteins implicated components of diverse
      overlapping pathways including the IL-6/phosphatidylinositol 3-kinase, insulin
      like growth factor 2/Ras/Raf, WNT8d/Frizzled, MAPK-activated protein kinase 2,
      and nuclear factor kappaB. The differential phosphorylation status of selected
      kinase-active proteins was validated by Western blotting analysis. Our
      complementary genomic and proteomic approach reveal the global cellular
      consequences of SB203580 treatment and provide insights into its growth
      inhibitory effect on transformed follicular lymphoma cells.

PMID- 15169873
TI  - Proteomic analysis of interchromatin granule clusters.
AB  - A variety of proteins involved in gene expression have been localized within
      mammalian cell nuclei in a speckled distribution that predominantly corresponds
      to interchromatin granule clusters (IGCs). We have applied a mass spectrometry
      strategy to identify the protein composition of this nuclear organelle purified
      from mouse liver nuclei. Using this approach, we have identified 146 proteins,
      many of which had already been shown to be localized to IGCs, or their functions
      are common to other already identified IGC proteins. In addition, we identified
      32 proteins for which only sequence information is available and thus these
      represent novel IGC protein candidates. We find that 54% of the identified IGC
      proteins have known functions in pre-mRNA splicing. In combination with proteins
      involved in other steps of pre-mRNA processing, 81% of the identified IGC
      proteins are associated with RNA metabolism. In addition, proteins involved in
      transcription, as well as several other cellular functions, have been identified
      in the IGC fraction. However, the predominance of pre-mRNA processing factors
      supports the proposed role of IGCs as assembly, modification, and/or storage
      sites for proteins involved in pre-mRNA processing.

PMID- 15169875
TI  - Identification and verification of novel rodent postsynaptic density proteins.
AB  - The postsynaptic density (PSD) is a cellular structure specialized in receiving
      and transducing synaptic information. Here we describe the identification of 452
      proteins isolated from biochemically purified PSD fractions of rat and mouse
      brains using nanoflow HPLC coupled to electrospray tandem mass spectrometry (LC
      MS/MS). Fluorescence microscopy and Western blotting were used to verify that
      many of the novel proteins identified exhibit subcellular distributions
      consistent with those of PSD-localized proteins. In addition to identifying most
      previously described PSD components, we also detected proteins involved in
      signaling to the nucleus as well as regulators of ADP-ribosylation factor
      signaling, ubiquitination, RNA trafficking, and protein translation. These
      results suggest new mechanisms by which the PSD helps regulate synaptic strength
      and transmission.

PMID- 15169876
TI  - Tumor viruses and cell signaling pathways: deubiquitination versus
      ubiquitination.

PMID- 15169877
TI  - A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain
      is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK
      snRNA-mediated inactivation of P-TEFb.
AB  - The HEXIM1 protein inhibits the kinase activity of P-TEFb (CDK9/cyclin T) to
      suppress RNA polymerase II transcriptional elongation in a process that
      specifically requires the 7SK snRNA, which mediates the interaction of HEXIM1
      with P-TEFb. In an attempt to define the sequence requirements for HEXIM1 to
      interact with 7SK and inactivate P-TEFb, we have identified the first 18 amino
      acids within the previously described nuclear localization signal (NLS) of HEXIM1
      as both necessary and sufficient for binding to 7SK in vivo and in vitro. This
      7SK-binding motif was essential for HEXIM1's inhibitory action, as the HEXIM1
      mutants with this motif replaced with a foreign NLS failed to interact with 7SK
      and P-TEFb and hence were unable to inactivate P-TEFb. The 7SK-binding motif
      alone, however, was not sufficient to inhibit P-TEFb. A region C-terminal to this
      motif was also required for HEXIM1 to associate with P-TEFb and suppress P-TEFb's
      kinase and transcriptional activities. The 7SK-binding motif in HEXIM1 contains
      clusters of positively charged residues reminiscent of the arginine-rich RNA
      binding motif found in a wide variety of proteins. Part of it is highly
      homologous to the TAR RNA-binding motif in the human immunodeficiency virus type
      1 (HIV-1) Tat protein, which was able to restore the 7SK-binding ability of a
      HEXIM1 NLS substitution mutant. We propose that a similar RNA-protein recognition
      mechanism may exist to regulate the formation of both the Tat-TAR-P-TEFb and the
      HEXIM1-7SK-P-TEFb ternary complexes, which may help convert the inactive
      HEXIM1/7SK-bound P-TEFb into an active one for Tat-activated and TAR-dependent
      HIV-1 transcription.

PMID- 15169879
TI  - Epidermal growth factor enhances cellular TATA binding protein levels and induces
      RNA polymerase I- and III-dependent gene activity.
AB  - TATA binding protein (TBP) is a central transcription factor used by all three
      cellular RNA polymerases. Changes in the levels of TBP have been shown to have
      selective effects on gene activity. Overexpression of TBP has been recently shown
      to contribute to cellular transformation, and elevated levels of TBP occur in a
      clinically significant proportion of human colon tumors relative to matched
      normal tissue. To understand the mechanisms by which TBP is regulated, we have
      analyzed whether activation of the epidermal growth factor receptor (EGFR), a
      membrane-bound tyrosine receptor kinase that is activated in a large number of
      human cancers, can serve to regulate cellular TBP. We show that treatment of
      mouse epidermal cells with EGF produces an increase in TBP levels, which can be
      blocked with an EGFR-specific inhibitor. In contrast, TBP levels remain unchanged
      after EGF treatment of EGFR null cells. EGF-mediated increases in TBP are
      regulated at the transcriptional level, as transient expression of the human TBP
      promoter is induced with EGF. This regulatory event is dependent upon the
      downstream activation of Ras and requires the activation of p38, JNK, and ERK
      mitogen-activated protein kinases. The consequence of elevated TBP on gene
      expression was further determined. Transcription by RNA polymerase (Pol) I and
      III was induced by EGF. Directly overexpressing TBP also stimulated transcription
      from these promoters. Thus, we have identified a new and important target of EGFR
      signaling, TBP, that contributes to EGF-mediated stimulation of RNA Pol I- and
      III-dependent gene activity. Since the cellular levels of the products of these
      genes, tRNAs and rRNAs, determine the translational capacity of cells, this event
      may be an important contributor to the transforming function of EGF.

PMID- 15169878
TI  - Activation of the growth-differentiation factor 11 gene by the histone
      deacetylase (HDAC) inhibitor trichostatin A and repression by HDAC3.
AB  - Histone deacetylase (HDAC) inhibitors inhibit the proliferation of transformed
      cells in vitro, restrain tumor growth in animals, and are currently being
      actively exploited as potential anticancer agents. To identify gene targets of
      the HDAC inhibitor trichostatin A (TSA), we compared the gene expression profiles
      of BALB/c-3T3 cells treated with or without TSA. Our results show that TSA up
      regulates the expression of the gene encoding growth-differentiation factor 11
      (Gdf11), a transforming growth factor beta family member that inhibits cell
      proliferation. Detailed analyses indicated that TSA activates the gdf11 promoter
      through a conserved CCAAT box element. A comprehensive survey of human HDACs
      revealed that HDAC3 is necessary and sufficient for the repression of gdf11
      promoter activity. Chromatin immunoprecipitation assays showed that treatment of
      cells with TSA or silencing of HDAC3 expression by small interfering RNA causes
      the hyperacetylation of Lys-9 in histone H3 on the gdf11 promoter. Together, our
      results provide a new model in which HDAC inhibitors reverse abnormal cell growth
      by inactivation of HDAC3, which in turn leads to the derepression of gdf11
      expression.

PMID- 15169880
TI  - A new Saccharomyces cerevisiae strain with a mutant Smt3-deconjugating Ulp1
      protein is affected in DNA replication and requires Srs2 and homologous
      recombination for its viability.
AB  - The Saccharomyces cerevisiae Srs2 protein is involved in DNA repair and
      recombination. In order to gain better insight into the roles of Srs2, we
      performed a screen to identify mutations that are synthetically lethal with an
      srs2 deletion. One of them is a mutated allele of the ULP1 gene that encodes a
      protease specifically cleaving Smt3-protein conjugates. This allele, ulp1-I615N,
      is responsible for an accumulation of Smt3-conjugated proteins. The mutant is
      unable to grow at 37 degrees C. At permissive temperatures, it still shows severe
      growth defects together with a strong hyperrecombination phenotype and is
      impaired in meiosis. Genetic interactions between ulp1 and mutations that affect
      different repair pathways indicated that the RAD51-dependent homologous
      recombination mechanism, but not excision resynthesis, translesion synthesis, or
      nonhomologous end-joining processes, is required for the viability of the mutant.
      Thus, both Srs2, believed to negatively control homologous recombination, and the
      process of recombination per se are essential for the viability of the ulp1
      mutant. Upon replication, mutant cells accumulate single-stranded DNA
      interruptions. These structures are believed to generate different recombination
      intermediates. Some of them are fixed by recombination, and others require Srs2
      to be reversed and fixed by an alternate pathway.

PMID- 15169881
TI  - Molecular dissection of 2B4 signaling: implications for signal transduction by
      SLAM-related receptors.
AB  - 2B4 is a SLAM-related receptor expressed on natural killer (NK) cells and
      cytotoxic T cells. It can regulate killing and gamma interferon secretion by NK
      cells, as well as T-cell-mediated cytotoxicity. There are conflicting data
      regarding the mechanism of action of 2B4. In these studies, we attempted to
      understand better the nature and basis of 2B4 signaling. Our studies showed that
      engagement of 2B4 on NK cells triggered a tyrosine phosphorylation signal
      implicating 2B4, Vav-1, and, to a lesser extent, SHIP-1 and c-Cbl. Structure
      function analyses demonstrated that this response was defined by a series of
      tyrosine-based motifs in the cytoplasmic region of 2B4 and was not influenced by
      the extracellular or transmembrane segment of 2B4. In addition, the 2B4-induced
      signal was absolutely dependent on coexpression of SAP, a Src homology 2 (SH2)
      domain-containing adaptor associating with SLAM-related receptors and mutated in
      X-linked lymphoproliferative disease. It was also observed that 2B4 was
      detectably associated with the Src-related protein tyrosine kinase FynT in an
      immortalized NK cell line. Mutation of arginine 78 of SAP, a residue critical for
      binding of SAP to FynT, eliminated 2B4-mediated protein tyrosine phosphorylation,
      implying that SAP promotes 2B4 signaling most probably by recruiting FynT.
      Finally, despite the similarities in the signaling modalities of 2B4 and its
      relative SLAM, the natures of the tyrosine phosphorylation signals induced by
      these two receptors were found to be different. These differences were not caused
      by variations in the extent of binding to SAP but rather were dictated by the
      tyrosine-based sequences in the cytoplasmic domain of the receptors. Taken
      together, these data lead to a better understanding of 2B4 signaling.
      Furthermore, they provide firm evidence that the signals transduced by the
      various SLAM-related receptors are unique and that the specificity of these
      signals is defined by the distinctive arrays of intracytoplasmic tyrosines in the
      receptors.

PMID- 15169883
TI  - Oxidative and osmotic stress signaling in tumor cells is mediated by ADAM
      proteases and heparin-binding epidermal growth factor.
AB  - Mammalian cells respond to environmental stress by activating a variety of
      protein kinases critical for cellular signal transmission, such as the epidermal
      growth factor receptor (EGFR) tyrosine kinase and different members of the
      mitogen-activated protein kinase (MAPK) family. EGFR activation by stress stimuli
      was previously thought to occur independently of stimulation by extracellular
      ligands. Here, we provide evidence that osmotic and oxidative stresses induce a
      metalloprotease activity leading to cell surface cleavage of pro-heparin-binding
      EGF (pro-HB-EGF) and subsequent EGFR activation. This ligand-dependent EGFR
      signal resulted from stress-induced activation of the MAPK p38 in human carcinoma
      cells and was mediated by the metalloproteases ADAM9, -10, and -17. Furthermore,
      stress-induced EGFR activation induced downstream signaling through the MAPKs
      extracellular signal-regulated kinases 1 and 2 and JNK. Interestingly, apoptosis
      induced by treatment of tumor cells with doxorubicin was strongly enhanced by
      blocking HB-EGF function. Together, our data provide novel insights into the
      mammalian stress response, suggesting a broad mechanistic relevance of a p38-ADAM
      HB-EGF-EGFR-dependent pathway and its potential significance for tumor cells in
      evasion of chemotherapeutic agent-induced apoptosis.

PMID- 15169882
TI  - ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell
      proliferation and antiestrogen resistance.
AB  - Overexpression or amplification of ACTR (also named AIB1, RAC3, p/CIP, TRAM-1,
      and SRC-3), a member of the p160 family of coactivators for nuclear hormone
      receptors, has been frequently detected in multiple types of human tumors,
      including breast cancer. However, its role in cancer cell proliferation and the
      underlying mechanism are unclear. Here, we show that overexpression of ACTR not
      only enhances estrogen-stimulated cell proliferation but also, more strikingly,
      completely negates the cell cycle arrest effect by tamoxifen and pure
      antiestrogens. Unexpectedly, we found that ACTR directly interacts, through its N
      terminal domain, with E2F1 and is recruited to E2F target gene promoters.
      Elevation of ACTR in quiescent cells strongly stimulates the transcription of a
      subset of E2F-responsive genes that are associated with the G(1)/S transition. We
      also demonstrated, by adenovirus vector-mediated RNA interference, that ACTR is
      required for E2F1-mediated gene expression and the proliferation of estrogen
      receptor (ER)-negative breast cancer cells. Moreover, the ability of elevated
      ACTR to promote estrogen-independent cell proliferation depends on the function
      of E2F1 and the association between ACTR and E2F1, but not ER. Thus, our results
      reveal an essential role of ACTR in control of breast cancer cell proliferation
      and implicate the ACTR-E2F1 pathway as a novel mechanism in antiestrogen
      resistance.

PMID- 15169884
TI  - Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone
      lysine methyltransferase through a unique C2HR motif.
AB  - Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and
      rearrangements of this gene by translocation can cause acute myeloid leukemia.
      The NSD1 gene product is a SET-domain histone lysine methyltransferase that has
      previously been shown to interact with nuclear receptors. We describe here a
      novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain,
      and four consensus C2H2-type zinc fingers preceded by a unique finger derivative,
      referred to herein as the C2HR motif. The C2HR motif functions to mediate protein
      protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)
      dependent fashion, and when tethered to RNA polymerase II promoters, represses
      transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine
      residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and
      compromise the ability of Nizp1 to repress transcription. Interestingly,
      converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect.
      Thus, Nizp1 contains a novel type of zinc finger motif that functions as a
      docking site for NSD1 and is more than just a degenerate evolutionary remnant of
      a C2H2 motif.

PMID- 15169885
TI  - Glucose and nitrogen regulate the switch from histone deacetylation to
      acetylation for expression of early meiosis-specific genes in budding yeast.
AB  - In eukaryotes, the switch between alternative developmental pathways is mainly
      attributed to a switch in transcriptional programs. A major mode in this switch
      is the transition between histone deacetylation and acetylation. In budding
      yeast, early meiosis-specific genes (EMGs) are repressed in the mitotic cell
      cycle by active deacetylation of their histones. Transcriptional activation of
      these genes in response to the meiotic signals (i.e., glucose and nitrogen
      depletion) requires histone acetylation. Here we follow how this regulated switch
      is accomplished, demonstrating the existence of two parallel mechanisms. (i) We
      demonstrate that depletion of glucose and nitrogen leads to a transient
      replacement of the histone deacetylase (HDAC) complex on the promoters of EMG by
      the transcriptional activator Ime1. The occupancy by either component occurs
      independently of the presence or absence of the other. Removal of the HDAC
      complex depends on the protein kinase Rim15, whose activity in the presence of
      nutrients is inhibited by protein kinase A phosphorylation. (ii) In the absence
      of glucose, HDAC loses its ability to repress transcription, even if this
      repression complex is directly bound to a promoter. We show that this relief of
      repression depends on Ime1, as well as on the kinase activity of Rim11, a
      glycogen synthase kinase 3beta homolog that phosphorylates Ime1. We further show
      that the glucose signal is transmitted through Rim11. In cells expressing the
      constitutive active rim11-3SA allele, HDAC repression in glucose medium is
      impaired.

PMID- 15169886
TI  - Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon
      receptor-dependent mechanism.
AB  - Human paraoxonase 1 (PON-1) is a serum high-density lipoprotein-associated enzyme
      mainly secreted by the liver. It has endogenous and exogenous substrates and
      displays protective properties with respect to cardiovascular disease and
      organophosphate intoxication. In the HuH7 human hepatoma cell line, PON-1
      activity and mRNA levels were increased by dietary polyphenolic compounds such as
      quercetin but also by toxic ligands of the aryl hydrocarbon receptor (AhR) such
      as 3-methylcholanthrene (3-MC). However, the 2,3,7,8-tetrachlorobenzo(p)dioxin
      (TCDD) was a poor inducer. Transient and stable transfection assays indicated
      that these compounds increased the PON-1 gene promoter activity in an AhR
      dependent manner, since their effect was inhibited by 7-keto-cholesterol and AhR
      directed short interfering RNA. Deletions and mutations studies showed that a
      xenobiotic responsive element (XRE)-like sequence within the PON-1 promoter
      mediated the effect of 3-MC and quercetin. In contrast with consensus XREs from
      the cytochrome P450 1A1 gene, the PON-1 XRE-like element mediated preferentially
      the effect of quercetin compared to the results seen with TCDD. Furthermore, AhR
      binding to this element was preferentially activated by quercetin. These
      observations provide a molecular mechanism for the regulation of the
      cardioprotective enzyme PON-1 by polyphenols. They suggest also that AhR ligands
      may differentially regulate gene expression depending on the DNA target sequence.

PMID- 15169887
TI  - Epstein-Barr virus latent membrane protein 1 induces synthesis of hypoxia
      inducible factor 1 alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix
      transcription factor composed of HIF-1 alpha and HIF-1 beta that is the central
      regulator of responses to hypoxia. The specific binding of HIF-1 to the hypoxia
      responsive element (HRE) induces the transcription of genes that respond to
      hypoxic conditions, including vascular endothelial growth factor (VEGF). Here we
      report that expression of HIF-1 alpha is increased in diverse Epstein-Barr virus
      (EBV)-infected type II and III cell lines, which express EBV latent membrane
      protein 1 (LMP1), the principal EBV oncoprotein, as well as other latency
      proteins, but not in the parental EBV-negative cell lines. We show first that
      transfection of an LMP1 expression plasmid into Ad-AH cells, an EBV-negative
      nasopharyngeal epithelial cell line, induces synthesis of HIF-1 alpha protein
      without increasing its stability or mRNA level. The mitogen-activated protein
      kinase (MAPK) kinase inhibitor PD98059 markedly reduces induction of HIF-1 alpha
      by LMP1. Catalase, an H(2)O(2) scavenger, strongly suppresses LMP1-induced
      production of H(2)O(2), which results in a decrease in the expression of HIF-1
      alpha induced by LMP1. Inhibition of the NF-kappa B, c-jun N-terminal kinase, p38
      MAPK, and phosphatidylinositol 3-kinase pathways did not affect HIF-1 alpha
      expression. Moreover, LMP1 induces HIF-1 DNA binding activity and upregulates HRE
      and VEGF promoter transcriptional activity. Finally, LMP1 increases the
      appearance of VEGF protein in extracellular fluids; induction of VEGF is
      suppressed by PD98059 or catalase. These results suggest that LMP1 increases HIF
      1 activity through induction of HIF-1 alpha protein expression, which is
      controlled by p42/p44 MAPK activity and H(2)O(2). The ability of EBV, and
      specifically its major oncoprotein, LMP1, to induce HIF-1 alpha along with other
      invasiveness and angiogenic factors reported previously discloses additional
      oncogenic properties of this tumor virus.

PMID- 15169888
TI  - ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential
      for TPL-2 protein stability.
AB  - NF-kappa B1 p105 forms a high-affinity, stoichiometric interaction with TPL-2, a
      MEK kinase essential for TLR4 activation of the ERK mitogen-activated protein
      kinase cascade in lipopolysaccharide (LPS)-stimulated macrophages. Interaction
      with p105 is required to maintain TPL-2 metabolic stability and also negatively
      regulates TPL-2 MEK kinase activity. Here, affinity purification identified A20
      binding inhibitor of NF-kappa B 2 (ABIN-2) as a novel p105-associated protein.
      Cotransfection experiments demonstrated that ABIN-2 could interact with TPL-2 in
      addition to p105 but preferentially formed a ternary complex with both proteins.
      Consistently, in unstimulated bone marrow-derived macrophages (BMDMs), a
      substantial fraction of endogenous ABIN-2 was associated with both p105 and TPL
      2. Although the majority of TPL-2 in these cells was complexed with ABIN-2, the
      pool of TPL-2 which could activate MEK after LPS stimulation was not, and LPS
      activation of TPL-2 was found to correlate with its release from ABIN-2.
      Depletion of ABIN-2 by RNA interference dramatically reduced steady-state levels
      of TPL-2 protein without affecting levels of TPL-2 mRNA or p105 protein. In
      addition, ABIN-2 increased the half-life of cotransfected TPL-2. Thus, optimal
      TPL-2 stability in vivo requires interaction with ABIN-2 as well as p105.
      Together, these data raise the possibility that ABIN-2 functions in the TLR4
      signaling pathway which regulates TPL-2 activation.

PMID- 15169889
TI  - Genome-wide analysis of the biology of stress responses through heat shock
      transcription factor.
AB  - Heat shock transcription factor (HSF) and the promoter heat shock element (HSE)
      are among the most highly conserved transcriptional regulatory elements in
      nature. HSF mediates the transcriptional response of eukaryotic cells to heat,
      infection and inflammation, pharmacological agents, and other stresses. While HSF
      is essential for cell viability in Saccharomyces cerevisiae, oogenesis and early
      development in Drosophila melanogaster, extended life span in Caenorhabditis
      elegans, and extraembryonic development and stress resistance in mammals, little
      is known about its full range of biological target genes. We used whole-genome
      analyses to identify virtually all of the direct transcriptional targets of yeast
      HSF, representing nearly 3% of the genomic loci. The majority of the identified
      loci are heat-inducibly bound by yeast HSF, and the target genes encode proteins
      that have a broad range of biological functions including protein folding and
      degradation, energy generation, protein trafficking, maintenance of cell
      integrity, small molecule transport, cell signaling, and transcription. This
      genome-wide identification of HSF target genes provides novel insights into the
      role of HSF in growth, development, disease, and aging and in the complex
      metabolic reprogramming that occurs in all cells in response to stress.

PMID- 15169890
TI  - Characterization of NF-kappa B/I kappa B proteins in zebra fish and their
      involvement in notochord development.
AB  - Although largely involved in innate and adaptive immunity, NF-kappa B plays an
      important role in vertebrate development. In chicks, the inactivation of the NF
      kappa B pathway induces functional alterations of the apical ectodermal ridge,
      which mediates limb outgrowth. In mice, the complete absence of NF-kappa B
      activity leads to prenatal death and neural tube defects. Here, we report the
      cloning and characterization of NF-kappa B/I kappa B proteins in zebra fish.
      Despite being ubiquitously expressed among the embryonic tissues, NF-kappa B/I
      kappa B members present distinct patterns of gene expression during the early
      zebra fish development. Biochemical assays indicate that zebra fish NF-kappa B
      proteins are able to bind consensus DNA-binding (kappa B) sites and inhibitory I
      kappa B alpha proteins from mammals. We show that zebra fish I kappa B alphas are
      degraded in a time-dependent manner after induction of transduced murine embryo
      fibroblasts (MEFs) and that these proteins are able to rescue NF-kappa B activity
      in I kappa B alpha(-/-) MEFs. Expression of a dominant-negative form of the
      murine I kappa B alpha (mI kappa B alpha M), which is able to block NF-kappa B in
      zebra fish cells, interferes with the notochord differentiation, generating no
      tail (ntl)-like embryos. This phenotype can be rescued by coinjection of the T
      box gene ntl (Brachyury homologue), which is typically required for the formation
      of posterior mesoderm and axial development, suggesting that ntl lies downstream
      of NF-kappa B . We further show that ntl and Brachyury promoter regions contain
      functional kappa B sites and NF-kappa B can directly modulate ntl expression. Our
      study illustrates the conservation and compatibility of NF-kappa B/I kappa B
      proteins among vertebrates and the importance of NF-kappa B pathway in mesoderm
      formation during early embryogenesis.

PMID- 15169891
TI  - Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism
      that controls its ability to activate N-WASP.
AB  - The Arp2/3 complex can be independently activated to initiate actin
      polymerization by the VCA domain of WASP family members and by the acidic N
      terminal and F-actin-binding repeat region of cortactin, which possesses a C
      terminal SH3 domain. Cortactin is a target for phosphorylation by Src tyrosine
      kinases and by serine/threonine kinases that include Erk. Here we demonstrate
      that cortactin binds N-WASP and WASP via its SH3 domain, induces in vitro N-WASP
      mediated actin polymerization, and colocalizes with N-WASP and WASP at sites of
      active actin polymerization. Erk phosphorylation and a mimicking S405,418D double
      mutation enhanced cortactin binding and activation of N-WASP. In contrast, Src
      phosphorylation inhibited the ability of cortactin previously phosphorylated by
      Erk, and that of S405,418D double mutant cortactin, to bind and activate N-WASP.
      Furthermore, Y-->D mutation of three tyrosine residues targeted by Src (Y421,
      Y466, and Y482) inhibited the ability of S405,418D cortactin to activate N-WASP.
      We propose that Erk phosphorylation liberates the SH3 domain of cortactin from
      intramolecular interactions with proline-rich regions, causing it to synergize
      with WASP and N-WASP in activating the Arp2/3 complex, and that Src
      phosphorylation terminates cortactin activation of N-WASP and WASP.

PMID- 15169893
TI  - Mutations in a partitioning protein and altered chromatin structure at the
      partitioning locus prevent cohesin recruitment by the Saccharomyces cerevisiae
      plasmid and cause plasmid missegregation.
AB  - The 2 microm circle is a highly persistent "selfish" DNA element resident in the
      Saccharomyces cerevisiae nucleus whose stability approaches that of the
      chromosomes. The plasmid partitioning system, consisting of two plasmid-encoded
      proteins, Rep1p and Rep2p, and a cis-acting locus, STB, apparently feeds into the
      chromosome segregation pathway. The Rep proteins assist the recruitment of the
      yeast cohesin complex to STB during the S phase, presumably to apportion the
      replicated plasmid molecules equally to daughter cells. The DNA-protein and
      protein-protein interactions of the partitioning system, as well as the chromatin
      organization at STB, are important for cohesin recruitment. Rep1p variants that
      are incompetent in binding to Rep2p, STB, or both fail to assist the assembly of
      the cohesin complex at STB and are nonfunctional in plasmid maintenance.
      Preventing the cohesin-STB association without impeding Rep1p-Rep2p-STB
      interactions also causes plasmid missegregation. During the yeast cell cycle, the
      Rep1p and Rep2p proteins are expelled from STB during a short interval between
      the late G(1) and early S phases. This dissociation and reassociation event
      ensures that cohesin loading at STB is replication dependent and is coordinated
      with chromosomal cohesin recruitment. In an rsc2 Delta yeast strain lacking a
      specific chromatin remodeling complex and exhibiting a high degree of plasmid
      loss, neither Rep1p nor the cohesin complex can be recruited to STB. The
      phenotypes of the Rep1p mutations and of the rsc2 Delta mutant are consistent
      with the role of cohesin in plasmid partitioning being analogous to that in
      chromosome partitioning.

PMID- 15169892
TI  - Targeted inactivation of serum response factor in the developing heart results in
      myocardial defects and embryonic lethality.
AB  - Serum response factor (SRF) is at the confluence of multiple signaling pathways
      controlling the transcription of immediate-early response genes and muscle
      specific genes. There are active SRF target sequences in more than 50 genes
      expressed in the three muscle lineages including normal and diseased hearts.
      However, the role of SRF in heart formation has not been addressed in vivo thus
      far due to the early requirement of SRF for mesoderm formation. We have generated
      a conditional mutant of SRF by using Cre-LoxP strategy that will be extremely
      useful to study the role of SRF in embryonic and postnatal cardiac functions, as
      well as in other tissues. This report shows that heart-specific deletion of SRF
      in the embryo by using a new beta MHC-Cre transgenic mouse line results in lethal
      cardiac defects between embryonic day 10.5 (E10.5) and E13.5, as evidenced by
      abnormally thin myocardium, dilated cardiac chambers, poor trabeculation, and a
      disorganized interventricular septum. At E9.5, we found a marked reduction in the
      expression of essential regulators of heart development, including Nkx2.5, GATA4,
      myocardin, and the SRF target gene c-fos prior to overt maldevelopment. We
      conclude that SRF is crucial for cardiac differentiation and maturation, acting
      as a global regulator of multiple developmental genes.

PMID- 15169894
TI  - Diet-induced obesity and reduced skin cancer susceptibility in matrix
      metalloproteinase 19-deficient mice.
AB  - Matrix metalloproteinase 19 (MMP-19) is a member of the MMP family of
      endopeptidases that, in contrast to most MMPs, is widely expressed in human
      tissues under normal quiescent conditions. MMP-19 has been found to be associated
      with ovulation and angiogenic processes and is deregulated in diverse
      pathological conditions such as rheumatoid arthritis and cancer. To gain further
      insights into the in vivo functions of this protease, we have generated mutant
      mice deficient in Mmp19. These mice are viable and fertile and do not display any
      obvious abnormalities. However, Mmp19-null mice develop a diet-induced obesity
      due to adipocyte hypertrophy and exhibit decreased susceptibility to skin tumors
      induced by chemical carcinogens. Based on these results, we suggest that this
      enzyme plays an in vivo role in some of the tissue remodeling events associated
      with adipogenesis, as well as in pathological processes such as tumor
      progression.

PMID- 15169895
TI  - Vault poly(ADP-ribose) polymerase is associated with mammalian telomerase and is
      dispensable for telomerase function and vault structure in vivo.
AB  - Vault poly(ADP-ribose) polymerase (VPARP) was originally identified as a minor
      protein component of the vault ribonucleoprotein particle, which may be involved
      in molecular assembly or subcellular transport. In addition to the association of
      VPARP with the cytoplasmic vault particle, subpopulations of VPARP localize to
      the nucleus and the mitotic spindle, indicating that VPARP may have other
      cellular functions. We found that VPARP was associated with telomerase activity
      and interacted with exogenously expressed telomerase-associated protein 1 (TEP1)
      in human cells. To study the possible role of VPARP in telomerase and vault
      complexes in vivo, mVparp-deficient mice were generated. Mice deficient in mVparp
      were viable and fertile for up to five generations, with no apparent changes in
      telomerase activity or telomere length. Vaults purified from mVparp-deficient
      mouse liver appeared intact, and no defect in association with other vault
      components was observed. Mice deficient in mTep1, whose disruption alone does not
      affect telomere function but does affect the stability of vault RNA, showed no
      additional telomerase or telomere-related phenotypes when the mTep1 deficiency
      was combined with an mVparp deficiency. These data suggest that murine mTep1 and
      mVparp, alone or in combination, are dispensable for normal development,
      telomerase catalysis, telomere length maintenance, and vault structure in vivo.

PMID- 15169896
TI  - The TALE homeodomain protein Pbx2 is not essential for development and long-term
      survival.
AB  - Pbx2 is one of four mammalian genes that encode closely related TALE homeodomain
      proteins, which serve as DNA binding partners for a subset of Hox transcription
      factors. The expression and contributions of Pbx2 to mammalian development remain
      undefined, in contrast to the essential roles recently established for family
      members Pbx1 and Pbx3. Here we report that Pbx2 is widely expressed during
      embryonic development, particularly in neural and epithelial tissues during late
      gestation. Despite wide Pbx2 expression, mice homozygous mutant for Pbx2 are born
      at the expected Mendelian frequencies and exhibit no detectable abnormalities in
      development and organogenesis or reduction of long-term survival. The lack of an
      apparent phenotype in Pbx2(-)/(-) mice likely reflects functional redundancy,
      since the Pbx2 protein is present at considerably lower levels than comparable
      isoforms of Pbx1 and/or Pbx3 in embryonic tissues. In postnatal bone marrow and
      thymus, however, Pbx2 is the predominant high-molecular-weight (MW)-isoform Pbx
      protein detectable by immunoblotting. Nevertheless, the absence of Pbx2 has no
      measurable effect on steady-state hematopoiesis or immune function in adult mice,
      suggesting possible compensation by low-MW-isoform Pbx proteins present in these
      tissues. We conclude that the roles of Pbx2 in murine embryonic development,
      organogenesis, hematopoiesis, immune responses, and long-term survival are not
      essential.

PMID- 15169897
TI  - Activation of a DNA damage checkpoint response in a TAF1-defective cell line.
AB  - Although the link between transcription and DNA repair is well established,
      defects in the core transcriptional complex itself have not been shown to elicit
      a DNA damage response. Here we show that a cell line with a temperature-sensitive
      defect in TBP-associated factor 1 (TAF1), a component of the TFIID general
      transcription complex, exhibits hallmarks of an ATR-mediated DNA damage response.
      Upon inactivation of TAF1, ATR rapidly localized to subnuclear foci and
      contributed to the phosphorylation of several downstream targets, including p53
      and Chk1, resulting in cell cycle arrest. The increase in p53 expression and the
      G(1) phase arrest could be blocked by caffeine, an inhibitor of ATR. In addition,
      dominant negative forms of ATR but not ATM were able to override the arrest in
      G(1). These results suggest that a defect in TAF1 can elicit a DNA damage
      response.

PMID- 15169899
TI  - FERM domain interaction promotes FAK signaling.
AB  - From the results of deletion analyses, the FERM domain of FAK has been proposed
      to inhibit enzymatic activity and repress FAK signaling. We have identified a
      sequence in the FERM domain that is important for FAK signaling in vivo. Point
      mutations in this sequence had little effect upon catalytic activity in vitro.
      However, the mutant exhibits reduced tyrosine phosphorylation and dramatically
      reduced Src family kinase binding. Further, the abilities of the mutant to
      transduce biochemical signals and to promote cell migration were severely
      impaired. The results implicate a FERM domain interaction in cell adhesion
      dependent activation of FAK and downstream signaling. We also show that the
      purified FERM domain of FAK interacts with full-length FAK in vitro, and mutation
      of this sequence disrupts the interaction. These findings are discussed in the
      context of models of FAK regulation by its FERM domain.

PMID- 15169900
TI  - Modulation of T-cell receptor signal transduction by herpesvirus signaling
      adaptor protein.
AB  - Because of its central regulatory role, T-cell receptor (TCR) signal transduction
      is a common target of viruses. We report here the identification of a small
      signaling protein, ORF5, of the T-lymphotropic tumor virus herpesvirus saimiri
      (HVS). ORF5 is predicted to contain 89 to 91 amino acids with an amino-terminal
      myristoylation site and six SH2 binding motifs, showing structural similarity to
      cellular LAT (linker for activation of T cells). Sequence analysis showed that,
      despite extensive sequence variation, the myristoylation site and SH2 binding
      motifs were completely conserved among 13 different ORF5 isolates. Upon TCR
      stimulation, ORF5 was efficiently tyrosine phosphorylated and subsequently
      interacted with cellular SH2-containing signaling proteins Lck, Fyn, SLP-76, and
      p85 through its tyrosine residues. ORF5 expression resulted in the marked
      augmentation of TCR signal transduction activity, evidenced by increased cellular
      tyrosine phosphorylation, intracellular calcium mobilization, CD69 surface
      expression, interleukin-2 production, and activation of the NF-AT, NF-kappa B,
      and AP-1 transcription factors. Despite its structural similarity to cellular
      LAT, however, ORF5 could only partially substitute for LAT function in TCR signal
      transduction. These results demonstrate that HVS utilizes a novel signaling
      protein, ORF5, to activate TCR signal transduction. This activation probably
      facilitates viral gene expression and, thereby, persistent infection.

PMID- 15169898
TI  - SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling
      pathway.
AB  - Myogenesis is an intricate process that coordinately engages multiple
      intracellular signaling cascades. The Rho family GTPase RhoA is known to promote
      myogenesis, however, the mechanisms controlling its regulation in myoblasts have
      yet to be fully elucidated. We show here that the SH2-containing protein tyrosine
      phosphatase, SHP-2, functions as an early modulator of myogenesis by regulating
      RhoA. When MyoD was expressed in fibroblasts lacking functional SHP-2, muscle
      specific gene activity was impaired and abolition of SHP-2 expression by RNA
      interference inhibited muscle differentiation. By using SHP-2 substrate-trapping
      mutants, we identified p190-B RhoGAP as a SHP-2 substrate. When dephosphorylated,
      p190-B RhoGAP has been shown to stimulate the activation of RhoA. During
      myogenesis, p190-B RhoGAP was tyrosyl dephosphorylated concomitant with the
      stimulation of SHP-2's phosphatase activity. Moreover, overexpression of a
      catalytically inactive mutant of SHP-2 inhibited p190-B RhoGAP tyrosyl
      dephosphorylation, RhoA activity, and myogenesis. These observations strongly
      suggest that SHP-2 dephosphorylates p190-B RhoGAP, leading to the activation of
      RhoA. Collectively, these data provide a mechanistic basis for RhoA activation in
      myoblasts and demonstrate that myogenesis is critically regulated by the actions
      of SHP-2 on the p190-B Rho GAP/RhoA pathway.

PMID- 15169903
TI  - RB reversibly inhibits DNA replication via two temporally distinct mechanisms.
AB  - The retinoblastoma (RB) tumor suppressor is a critical negative regulator of
      cellular proliferation. Repression of E2F-dependent transcription has been
      implicated as the mechanism through which RB inhibits cell cycle progression.
      However, recent data have suggested that the direct interaction of RB with
      replication factors or sites of DNA synthesis may contribute to its ability to
      inhibit S phase. Here we show that RB does not exert a cis-acting effect on DNA
      replication. Furthermore, the localization of RB was distinct from replication
      foci in proliferating cells. While RB activation strongly attenuated the RNA
      levels of multiple replication factors, their protein expression was not
      diminished coincident with cell cycle arrest. During the first 24 h of RB
      activation, components of the prereplication complex, initiation factors, and the
      clamp loader complex (replication factor C) remained tethered to chromatin. In
      contrast, the association of PCNA and downstream components of the processive
      replication machinery was specifically disrupted. This signaling from RB occurred
      in a manner dependent on E2F-mediated transcriptional repression. Following long
      term activation of RB, we observed the attenuation of multiple replication
      factors, the complete cessation of DNA synthesis, and impaired replicative
      capacity in vitro. Therefore, functional distinctions exist between the "chronic"
      RB-mediated arrest state and the "acute" arrest state. Strikingly, attenuation of
      RB activity reversed both acute and chronic replication blocks. Thus, continued
      RB action is required for the maintenance of two kinetically and functionally
      distinct modes of replication inhibition.

PMID- 15169902
TI  - Histone mRNAs do not accumulate during S phase of either mitotic or
      endoreduplicative cycles in the chordate Oikopleura dioica.
AB  - Metazoan histones are generally classified as replication-dependent or
      replacement variants. Replication-dependent histone genes contain cell cycle
      responsive promoter elements, their transcripts terminate in an unpolyadenylated
      conserved stem-loop, and their mRNAs accumulate sharply during S phase.
      Replacement variant genes lack cell cycle-responsive promoter elements, their
      polyadenylated transcripts lack the stem-loop, and they are expressed at low
      levels throughout the cell cycle. During early development of some organisms with
      rapid cleavage cycles, replication-dependent mRNAs are not fully S phase
      restricted until complete cell cycle regulation is achieved. The accumulation of
      polyadenylated transcripts during this period has been considered incompatible
      with metazoan development. We show here that histone metabolism in the
      urochordate Oikopleura dioica does not accord with some key tenets of the
      replication-dependent/replacement variant paradigm. During the premetamorphic
      mitotic phase of development, expressed variants shared characteristics of
      replication-dependent histones, including the 3' stem-loop, but, in contrast,
      were extensively polyadenylated. After metamorphosis, when cells in many tissues
      enter endocycles, there was a global downregulation of histone transcript levels,
      with most variant transcripts processed at the stem-loop. Contrary to the 30-fold
      S-phase upregulation of histone transcripts described in common metazoan model
      organisms, we observed essentially constant histone transcript levels throughout
      both mitotic and endoreduplicative cell cycles.

PMID- 15169901
TI  - Deletion of the mouse P450c17 gene causes early embryonic lethality.
AB  - Dehydroepiandrosterone (DHEA), a 19-carbon precursor of sex steroids, is
      abundantly produced in the human but not the mouse adrenal. However, mice produce
      DHEA and DHEA-sulfate (DHEAS) in the fetal brain. DHEA stimulates axonal growth
      from specific populations of mouse neocortical neurons in vitro, while DHEAS
      stimulates dendritic growth from those cells. The synthesis of DHEA and sex
      steroids, but not mouse glucocorticoids and mineralocorticoids, requires P450c17,
      which catalyzes both 17 alpha-hydroxylase and 17,20-lyase activities. We
      hypothesized that P450c17-knockout mice would have disordered sex steroid
      synthesis and disordered brain DHEA production and thus provide phenotypic clues
      about the functions of DHEA in mouse brain development. We deleted the mouse
      P450c17 gene in 127/SvJ mice and obtained several lines of mice from two lines of
      targeted embryonic stem cells. Heterozygotes were phenotypically and
      reproductively normal, but in all mouse lines, P450c17(-/-) zygotes died by
      embryonic day 7, prior to gastrulation. The cause of this early lethality is
      unknown, as there is no known function of fetal steroids at embryonic day 7.
      Immunocytochemistry identified P450c17 in embryonic endoderm in E7 wild-type and
      heterozygous embryos, but its function in these cells is unknown. Enzyme assays
      of wild-type embryos showed a rapid rise in 17-hydroxylase activity between E6
      and E7 and the presence of C(17,20)-lyase activity at E7. Treatment of pregnant
      females with subcutaneous pellets releasing DHEA or 17-OH pregnenolone at a
      constant rate failed to rescue P450c17(-/-) fetuses. Treatment of normal pregnant
      females with pellets releasing pregnenolone or progesterone did not cause fetal
      demise. These data suggest that steroid products of P450c17 have heretofore
      unknown essential functions in early embryonic mouse development.

PMID- 15169904
TI  - Role of pescadillo and upstream binding factor in the proliferation and
      differentiation of murine myeloid cells.
AB  - Pescadillo (PES1) and the upstream binding factor (UBF1) play a role in ribosome
      biogenesis, which regulates cell size, an important component of cell
      proliferation. We have investigated the effects of PES1 and UBF1 on the growth
      and differentiation of cell lines derived from 32D cells, an interleukin-3 (IL-3)
      dependent murine myeloid cell line. Parental 32D cells and 32D IGF-IR cells
      (expressing increased levels of the type 1 insulin-like growth factor I [IGF-I]
      receptor [IGF-IR]) do not express insulin receptor substrate 1 (IRS-1) or IRS-2.
      32D IGF-IR cells differentiate when the cells are shifted from IL-3 to IGF-I.
      Ectopic expression of IRS-1 inhibits differentiation and transforms 32D IGF-IR
      cells into a tumor-forming cell line. We found that PES1 and UBF1 increased cell
      size and/or altered the cell cycle distribution of 32D-derived cells but failed
      to make them IL-3 independent. PES1 and UBF1 also failed to inhibit the
      differentiation program initiated by the activation of the IGF-IR, which is
      blocked by IRS-1. 32D IGF-IR cells expressing PES1 or UBF1 differentiate into
      granulocytes like their parental cells. In contrast, PES1 and UBF1 can transform
      mouse embryo fibroblasts that have high levels of endogenous IRS-1 and are not
      prone to differentiation. Our results provide a model for one of the theories of
      myeloid leukemia, in which both a stimulus of proliferation and a block of
      differentiation are required for leukemia development.

PMID- 15169905
TI  - Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance
      through inhibition of tyrosine phosphorylation of insulin receptor substrate
      proteins by discrete mechanisms.
AB  - Insulin resistance is a pathophysiological component of type 2 diabetes and
      obesity and also occurs in states of stress, infection, and inflammation
      associated with an upregulation of cytokines. Here we show that in both obesity
      and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in
      suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver,
      muscle, and, to a lesser extent, fat. In concordance with these increases by LPS,
      tyrosine phosphorylation of the insulin receptor (IR) is partially impaired and
      phosphorylation of the insulin receptor substrate (IRS) proteins is almost
      completely suppressed. Direct overexpression of SOCS-3 in liver by adenoviral
      mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1
      and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2
      phosphorylation. Neither affects IR phosphorylation, although both SOCS-1 and
      SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
      Experiments with cultured cells expressing mutant insulin receptors reveal that
      SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS
      2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2
      recognition in vitro. Moreover, overexpression of either SOCS-1 or SOCS-3
      attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of
      glucose uptake in 3T3L1 adipocytes. By contrast, a reduction of SOCS-1 or SOCS-3
      by antisense treatment partially restores tumor necrosis factor alpha-induced
      downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
      These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin
      signaling and serve as one of the missing links between insulin resistance and
      cytokine signaling.

PMID- 15169906
TI  - Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic
      pathway.
AB  - Glucose homeostasis is controlled in part by regulation of glucose uptake into
      muscle and adipose tissue. Intracellular membrane vesicles containing the GLUT4
      glucose transporter move towards the cell cortex in response to insulin and then
      fuse with the plasma membrane. Here we show that the fusion step is retarded by
      the inhibition of phosphatidylinositol (PI) 3-kinase. Treatment of insulin
      stimulated 3T3-L1 adipocytes with the PI 3-kinase inhibitor LY294002 causes the
      accumulation of GLUT4-containing vesicles just beneath the cell surface. This
      accumulation of GLUT4-containing vesicles near the plasma membrane prior to
      fusion requires an intact cytoskeletal network and the unconventional myosin
      motor Myo1c. Remarkably, enhanced Myo1c expression under these conditions causes
      extensive membrane ruffling and overrides the block in membrane fusion caused by
      LY294002, restoring the display of GLUT4 on the cell exterior. Ultrafast
      microscopic analysis revealed that insulin treatment leads to the mobilization of
      GLUT4-containing vesicles to these regions of Myo1c-induced membrane ruffles.
      Thus, localized membrane remodeling driven by the Myo1c motor appears to
      facilitate the fusion of exocytic GLUT4-containing vesicles with the adipocyte
      plasma membrane.

PMID- 15169907
TI  - Mitogen stimulation cooperates with telomere shortening to activate DNA damage
      responses and senescence signaling.
AB  - Replicative senescence is induced by critical telomere shortening and limits the
      proliferation of primary cells to a finite number of divisions. To characterize
      the activity status of the replicative senescence program in the context of cell
      cycle activity, we analyzed the senescence phenotypes and signaling pathways in
      quiescent and growth-stimulated primary human fibroblasts in vitro and liver
      cells in vivo. This study shows that replicative senescence signaling operates at
      a low level in cells with shortened telomeres but becomes fully activated when
      cells are stimulated to enter the cell cycle. This study also shows that the
      dysfunctional telomeres and nontelomeric DNA lesions in senescent cells do not
      elicit a DNA damage signal unless the cells are induced to enter the cell cycle
      by mitogen stimulation. The amplification of senescence signaling and DNA damage
      responses by mitogen stimulation in cells with shortened telomeres is mediated in
      part through the MEK/mitogen-activated protein kinase pathway. These findings
      have implications for the further understanding of replicative senescence and
      analysis of its role in vivo.

PMID- 15169908
TI  - Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X
      chromosome.
AB  - Histone H3 tail modifications are among the earliest chromatin changes in the X
      chromosome inactivation process. In this study we investigated the relative
      profiles of two important repressive marks on the X chromosome: methylation of H3
      lysine 9 (K9) and 27 (K27). We found that both H3K9 dimethylation and K27
      trimethylation characterize the inactive X in somatic cells and that their
      relative kinetics of enrichment on the X chromosome as it undergoes inactivation
      are similar. However, dynamic changes of H3K9 and H3K27 methylation on the
      inactivating X chromosome compared to the rest of the genome are distinct,
      suggesting that these two modifications play complementary and perhaps
      nonredundant roles in the establishment and/or maintenance of X inactivation.
      Furthermore, we show that a hotspot of H3K9 dimethylation 5' to Xist also
      displays high levels of H3 tri-meK27. However, analysis of this region in G9a
      mutant embryonic stem cells shows that these two methyl marks are dependent on
      different histone methyltransferases.

PMID- 15169909
TI  - The ubiquitin-conjugating DNA repair enzyme HR6A is a maternal factor essential
      for early embryonic development in mice.
AB  - The Saccharomyces cerevisiae RAD6 protein is required for a surprising diversity
      of cellular processes, including sporulation and replicational damage bypass of
      DNA lesions. In mammals, two RAD6-related genes, HR6A and HR6B, encode highly
      homologous proteins. Here, we describe the phenotype of cells and mice deficient
      for the mHR6A gene. Just like mHR6B knockout mouse embryonic fibroblasts, mHR6A
      deficient cells appear to have normal DNA damage resistance properties, but mHR6A
      knockout male and female mice display a small decrease in body weight. The
      necessity for at least one functional mHR6A (X-chromosomal) or mHR6B (autosomal)
      allele in all somatic cell types is supported by the fact that neither animals
      lacking both proteins nor females with only one intact mHR6A allele are viable.
      In striking contrast to mHR6B knockout males, which show a severe spermatogenic
      defect, mHR6A knockout males are normally fertile. However, mHR6A knockout
      females fail to produce offspring despite a normal ovarian histology and
      ovulation. The absence of mHR6A in oocytes prevents development beyond the
      embryonic two-cell stage but does not result in an aberrant methylation pattern
      of histone H3 at this early stage of mouse embryonic development. These
      observations support redundant but dose-dependent roles for HR6A and HR6B in
      somatic cell types and germ line cells in mammals.

PMID- 15169910
TI  - Coordination of cell signaling, chromatin remodeling, histone modifications, and
      regulator recruitment in human matrix metalloproteinase 9 gene transcription.
AB  - Transcriptional activation of eukaryotic genes depends on the precise and ordered
      recruitment of activators, chromatin modifiers/remodelers, coactivators, and
      general transcription factors to the promoters of target genes. Using the human
      matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the
      sequential assembly and dynamic formation of transcription complexes on a human
      promoter under the influence of mitogen signaling. We find that, coincident with
      activation of the MMP-9 gene, activators, chromatin remodeling complexes, and
      coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and
      coordinated order, which is dependent on activation of MEK-1/extracellular signal
      regulated kinase and NF-kappa B signaling pathways. Conversely, corepressor
      complexes are released from the MMP-9 promoter after transcriptional activation.
      Histone modifications shift from repressive to permissive modifications
      concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg
      1 is required for MMP-9 gene transcription, which is concomitant with initiation
      of transcription. Therefore, coordination of cell signaling, chromatin
      remodeling, histone modifications, and stepwise recruitment of transcription
      regulators is critical to precisely regulate MMP-9 gene transcription in a
      temporally and spatially dependent manner. Given the important role of MMP-9 in
      both normal development and pathological conditions, understanding MMP-9 gene
      regulation is of great relevance.

PMID- 15169911
TI  - Impaired alveologenesis and maintenance of secretory mammary epithelial cells in
      Jak2 conditional knockout mice.
AB  - Jak2 is a hormone-receptor-coupled kinase that mediates the tyrosine
      phosphorylation and activation of signal transducers and activators of
      transcription (Stat). The biological relevance of Jak2-Stat signaling in hormone
      responsive adult tissues is difficult to investigate since Jak2 deficiency leads
      to embryonic lethality. We generated Jak2 conditional knockout mice to study
      essential functions of Jak2 during mammary gland development. The mouse mammary
      tumor virus-Cre-mediated excision of the first coding exon resulted in a Jak2
      null mutation that uncouples signaling from the prolactin receptor (PRL-R) to its
      downstream mediator Stat5 in the presence of normal and supraphysiological levels
      of PRL. Jak2-deficient females were unable to lactate as a result of impaired
      alveologenesis. Unlike Stat5a knockouts, multiple gestation cycles could not
      reverse the Jak2-deficient phenotype, suggesting that neither other components of
      the PRL-R signaling cascade nor other growth factors and their signal transducers
      were able to compensate for the loss of Jak2 function to activate Stat5 in vivo.
      A comparative analysis of Jak2-deficient mammary glands with transplants from
      Stat5a/b knockouts revealed that Jak2 deficiency also impairs the pregnancy
      induced branching morphogenesis. Jak2 conditional mutants therefore resemble PRL
      R knockouts more closely, which suggested that Jak2 deficiency might affect
      additional PRL-R downstream mediators other than Stat5a and Stat5b. To address
      whether Jak2 is required for the maintenance of PRL-responsive, differentiating
      alveolar cells, we utilized a transgenic strain that expresses Cre recombinase
      under regulatory elements of the whey acidic protein gene (Wap). The Wap-Cre
      mediated excision of Jak2 resulted in a negative selection of differentiated
      alveolar cells, suggesting that Jak2 is required not only for the proliferation
      and differentiation of alveolar cells but also for their maintenance during
      lactation.

PMID- 15169912
TI  - Positive and negative regulation of poly(A) nuclease.
AB  - PAN, a yeast poly(A) nuclease, plays an important nuclear role in the
      posttranscriptional maturation of mRNA poly(A) tails. The activity of this enzyme
      is dependent on its Pan2p and Pan3p subunits, as well as the presence of poly(A)
      binding protein (Pab1p). We have identified and characterized the associated
      network of factors controlling the maturation of mRNA poly(A) tails in yeast and
      defined its relevant protein-protein interactions. Pan3p, a positive regulator of
      PAN activity, interacts with Pab1p, thus providing substrate specificity for this
      nuclease. Pab1p also regulates poly(A) tail trimming by interacting with Pbp1p, a
      factor that appears to negatively regulate PAN. Pan3p and Pbp1p both interact
      with themselves and with the C terminus of Pab1p. However, the domains required
      for Pan3p and Pbp1p binding on Pab1p are distinct. Single amino acid changes that
      disrupt Pan3p interaction with Pab1p have been identified and define a binding
      pocket in helices 2 and 3 of Pab1p's carboxy terminus. The importance of these
      amino acids for Pab1p-Pan3p interaction, and poly(A) tail regulation, is
      underscored by experiments demonstrating that strains harboring substitutions in
      these residues accumulate mRNAs with long poly(A) tails in vivo.

PMID- 15169915
TI  - Akt mediates Ras downregulation of RhoB, a suppressor of transformation,
      invasion, and metastasis.
AB  - Although recent evidence supports a tumor-suppressive role for the GTPase RhoB,
      little is known about its regulation by signal transduction pathways. Here we
      demonstrate that Ras downregulates RhoB expression by a phosphatidylinositol 3
      kinase (PI3K)- and Akt- but not Mek-dependent mechanism. Furthermore, genetic and
      pharmacological blockade of PI3K/Akt results in upregulation of RhoB expression.
      We also provide evidence for the importance of the downregulation of RhoB in
      oncogenesis by demonstrating that RhoB antagonizes Ras/PI3K/Akt malignancy.
      Ectopic expression of RhoB, but not the close relative RhoA, inhibits Ras, PI3K,
      and Akt induction of transformation, migration, and invasion and induces
      apoptosis and anoikis. Finally, RhoB inhibits melanoma metastasis to the lung in
      a mouse model. These studies identify suppression of RhoB as a mechanism by which
      the Ras/PI3K/Akt pathway induces tumor survival, transformation, invasion, and
      metastasis.

PMID- 15169913
TI  - Genome-wide analysis of mRNA stability using transcription inhibitors and
      microarrays reveals posttranscriptional control of ribosome biogenesis factors.
AB  - Using DNA microarrays, we compared global transcript stability profiles following
      chemical inhibition of transcription to rpb1-1 (a temperature-sensitive allele of
      yeast RNA polymerase II). Among the five inhibitors tested, the effects of
      thiolutin and 1,10-phenanthroline were most similar to rpb1-1. A comparison to
      various microarray data already in the literature revealed similarity between
      mRNA stability profiles and the transcriptional response to stresses such as heat
      shock, consistent with the fact that the general stress response includes a
      transient shutoff of general mRNA transcription. Genes encoding factors involved
      in rRNA synthesis and ribosome assembly, which are often observed to be
      coordinately down-regulated in yeast microarray data, were among the least stable
      transcripts. We examined the effects of deletions of genes encoding deadenylase
      components Ccr4p and Pan2p and putative RNA-binding proteins Pub1p and Puf4p on
      the genome-wide pattern of mRNA stability after inhibition of transcription by
      chemicals and/or heat stress. This examination showed that Ccr4p, the major yeast
      mRNA deadenylase, contributes to the degradation of transcripts encoding both
      ribosomal proteins and rRNA synthesis and ribosome assembly factors and mediates
      a large part of the transcriptional response to heat stress. Pan2p and Puf4p also
      contributed to the degradation rate of these mRNAs following transcriptional
      shutoff, while Pub1p preferentially stabilized transcripts encoding ribosomal
      proteins. Our results indicate that the abundance of ribosome biogenesis factors
      is controlled at the level of mRNA stability.

PMID- 15169914
TI  - The ETS transcription factor ESE-1 transforms MCF-12A human mammary epithelial
      cells via a novel cytoplasmic mechanism.
AB  - Several different transcription factors, including estrogen receptor,
      progesterone receptor, and ETS family members, have been implicated in human
      breast cancer, indicating that transcription factor-induced alterations in gene
      expression underlie mammary cell transformation. ESE-1 is an epithelium-specific
      ETS transcription factor that contains two distinguishing domains, a serine- and
      aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly
      expressed in human breast cancer and trans-activates epithelium-specific gene
      promoters in transient transfection assays. While it has been presumed that ETS
      factors transform mammary epithelial cells via their nuclear transcriptional
      functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast
      cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1
      transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR
      domain, acting in the cytoplasm, is necessary and sufficient to mediate this
      transformation. Deletion of transcriptional regulatory or nuclear localization
      domains does not impair ESE-1-mediated transformation, whereas fusing the simian
      virus 40 T-antigen nuclear localization signal to various ESE-1 constructs,
      including the SAR domain alone, inhibits their transforming capacity. Finally, we
      show that the nuclear localization of ESE-1 protein induces apoptosis in
      nontransformed mammary epithelial cells via a transcription-dependent mechanism.
      Together, our studies reveal two distinct ESE-1 functions, apoptosis and
      transformation, where the ESE-1 transcription activation domain contributes to
      apoptosis and the SAR domain mediates transformation via a novel nonnuclear,
      nontranscriptional mechanism. These studies not only describe a unique ETS factor
      transformation mechanism but also establish a new paradigm for cell
      transformation in general.

PMID- 15169916
TI  - Protein inhibitor of activated STAT Y (PIASy) and a splice variant lacking exon 6
      enhance sumoylation but are not essential for embryogenesis and adult life.
AB  - Protein inhibitor of activated STAT Y (PIASy) is the shortest member of the PIAS
      family and has been reported to modulate the transcriptional activities of STAT1,
      lymphoid enhancer factor 1 (LEF-1), and the androgen receptor. PIAS proteins have
      also been identified as E3 ligases for the small ubiquitin-like modifier (SUMO)
      proteins. PIASy in particular has been reported to mediate SUMO-2/3 modification
      of LEF-1, sequestering it into nuclear bodies, and SUMO-1 ligation to c-Myb,
      modulating its transcriptional activation properties. We have cloned murine Piasy
      and a splice variant which omits exon 6, containing the nuclear retention PINIT
      motif. Cell culture studies indicate that both the full length and the splice
      variant are localized in the nucleus but differentially enhance SUMO ligation. To
      further understand the functions of PIASy, we have generated PIASy-deficient
      mice. Surprisingly, Piasy(-/-) mice appear phenotypically normal. Activation of
      STAT1 is not significantly perturbed in Piasy(-/-) cells, and sumoylation
      patterns for SUMO-1 or SUMO-3 modification are similar when comparing tissues and
      embryonic fibroblasts from wild-type and knockout mice. Our study demonstrates
      that at steady state, PIASy is either dispensable or compensated for by other
      PIAS family members or by other mechanisms when deleted.

PMID- 15169917
TI  - Dynamics of protein binding to telomeres in living cells: implications for
      telomere structure and function.
AB  - Telomeric proteins have an essential role in the regulation of the length of the
      telomeric DNA tract and in protection against end-to-end chromosome fusion.
      Telomere organization and how individual proteins are involved in different
      telomere functions in living cells is largely unknown. By using green fluorescent
      protein tagging and photobleaching, we investigated in vivo interactions of human
      telomeric DNA-binding proteins with telomeric DNA. Our results show that
      telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2,
      which has a dual role in chromosome end protection and telomere length
      homeostasis, resides at telomeres in two distinct pools. One fraction (
      approximately 73%) has binding dynamics similar to TRF1 (residence time of
      approximately 44 s). Interestingly, the other fraction of TRF2 binds with similar
      dynamics as the putative end-protecting factor hPOT1 (residence time of
      approximately 11 min). Our data support a dynamic model of telomeres in which
      chromosome end-protection and telomere length homeostasis are governed by
      differential binding of telomeric proteins to telomeric DNA.

PMID- 15169918
TI  - Bag-1 internal ribosome entry segment activity is promoted by structural changes
      mediated by poly(rC) binding protein 1 and recruitment of polypyrimidine tract
      binding protein 1.
AB  - We have shown previously that an internal ribosome entry segment (IRES) directs
      the synthesis of the p36 isoform of Bag-1 and that polypyrimidine tract binding
      protein 1 (PTB-1) and poly(rC) binding protein 1 (PCBP1) stimulate IRES-mediated
      translation initiation in vitro and in vivo. Here, a secondary structural model
      of the Bag-1 IRES has been derived by using chemical and enzymatic probing data
      as constraints on the RNA folding algorithm Mfold. The ribosome entry window has
      been identified within this structural model and is located in a region in which
      many residues are involved in base-pairing interactions. The interactions of PTB
      1 and PCBP1 with their cognate binding sites on the IRES disrupt many of the RNA
      RNA interactions, and this creates a largely unstructured region of approximately
      40 nucleotides that could permit ribosome binding. Mutational analysis of the PTB
      1 and PCBP1 binding sites suggests that PCBP1 acts as an RNA chaperone to open
      the RNA in the vicinity of the ribosome entry window while PTB-1 is probably an
      essential part of the preinitiation complex.

PMID- 15169919
TI  - Docking-dependent regulation of the Rb tumor suppressor protein by Cdk4.
AB  - Phosphorylation of target proteins by cyclin D1-Cdk4 requires both substrate
      docking and kinase activity. In addition to the ability of cyclin D1-Cdk4 to
      catalyze the phosphorylation of consensus sites within the primary amino acid
      sequence of a substrate, maximum catalytic activity requires the enzyme complex
      to anchor at a site remote from the phospho-acceptor site. A novel Cdk4 docking
      motif has been defined within a stretch of 19 amino acids from the C-terminal
      domain of the Rb protein that are essential for Cdk4 binding. Mutation or
      deletion of the docking motif prevents Cdk4-dependent phosphorylation of full
      length Rb protein or C-terminal Rb fragments in vitro and in cells, while a
      peptide encompassing the Cdk4 docking motif specifically inhibits Cdk4-dependent
      phosphorylation of Rb. Cyclin D1-Cdk4 can overcome the growth-suppressive
      activity of Rb in both cell cycle progression and colony formation assays;
      however, while mutants of Rb in which the Cdk4 docking site has been either
      deleted or mutated retain growth suppressor activity, they are resistant to
      inactivation by cyclin D1-Cdk4. Finally, binding of Cdk4 to its docking site can
      inhibit cleavage of exogenous and endogenous Rb in response to distinct apoptotic
      signals. The Cdk4 docking motif in Rb gives insight into the mechanism by which
      enzyme specificity is ensured and highlights a role for Cdk4 docking in
      maintaining the Rb protein in a form that favors cell survival rather than
      apoptosis.

PMID- 15169920
TI  - Characterization of a mouse recombination hot spot locus encoding a novel non
      protein-coding RNA.
AB  - Our current knowledge of recombination hot spot activity in mammalian systems
      implicates a role for both the primary DNA sequence and the nature of the
      chromatin domain around it. In mice, the only recombination hot spots mapped to
      date have been confined to a cluster within the major histocompatibility complex
      (MHC) region. We present a high resolution analysis of a new recombination hot
      spot in the mouse genome which maps to mouse chromosome 8 C-D. Haplotype
      diversity analysis across 40 different strains of mice has enabled us to map
      recombination breakpoints to a 1-kb interval. This hot spot has a recombination
      intensity that is 10- to 100-fold above the genome average and has a mean gene
      conversion tract length of 371 bp. This meiotically active locus happens to be
      flanked by a transcribed region encoding a non-protein-coding RNA polymerase II
      transcript and the previously characterized repair site. Many of the primary DNA
      sequence features that have been reported for the mouse MHC hot spots are also
      shared by this hot spot locus and in addition, along with three other MHC hot
      spot loci, we show a new parallel feature of association of the crossover sites
      with the nuclear matrix.

PMID- 15169921
TI  - Localization and synthesis of zona pellucida proteins in the marmoset monkey
      (Callithrix jacchus) ovary.
AB  - In most species, the zona pellucida (ZP), an extracellular matrix surrounding the
      mammalian oocyte, is composed of three glycoproteins: ZPA, ZPB and ZPC. Based
      mainly on results with mice, the site of zona pellucida biosynthesis has been
      suggested to be exclusively in the oocyte cytoplasm. However, evidence is
      accumulating that among various species cumulus/granulosa cells may be involved.
      Because knowledge of ZP biosynthesis in primates is lacking, we used the common
      marmoset (Callithrix jacchus) to acquire information about the localization and
      the site of synthesis of ZP proteins in this species. Using antibodies against
      synthetic ZPA and ZPC peptides, immunoreactivity was found in the marmoset ZP and
      in surrounding cumulus cells. Interestingly, the amounts of ZPA and ZPC proteins
      expressed appeared to differ depending on the stage of folliculogenesis. RT-PCR
      analysis of mRNA from marmoset oocytes and from oocyte-free follicle cells
      revealed expression of ZPA, ZPB and ZPC in oocytes and in follicle cells of
      different stages of marmoset monkey folliculogenesis. Our data suggest that the
      biosynthesis of marmoset ZPA, ZPB and ZPC proteins takes place both in oocytes
      and in follicle cells of different follicle stages, although the abundance of ZP
      glycoproteins may differ depending on the individual ZP protein.

PMID- 15169922
TI  - Influence of macrophage migration inhibitory factor (MIF) on the zinc content and
      redox state of protein-bound sulphydryl groups in rat sperm: indications for a
      new role of MIF in sperm maturation.
AB  - The function of macrophage migration inhibitory factor (MIF) in sperm maturation
      was studied by investigating its role in the biochemical maturation of the outer
      dense fibres. Rat sperm obtained from the caput and cauda epididymis were
      stimulated overnight with either recombinant MIF or MIF-containing vesicles
      originating from epididymal fluid at various concentrations. The zinc content of
      both the sperm and the medium was determined by means of atomic absorption
      spectrometry. Incubation in both recombinant MIF and vesicular MIF resulted in a
      statistically significant decrease of the zinc content in stimulated caput sperm
      of approximately 50%. In parallel, the conditioned media showed a clear increase
      in the concentration of this trace metal. The effect of MIF was less marked in
      cauda sperm. In addition, we demonstrated a statistically significant increase of
      detectable free thiol groups in the sperm mid- and principle piece in isolated
      rat sperm after stimulation with MIF at concentrations of 25 and 50 ng/ml. Our
      data suggest that MIF plays an important role in the maturation process of rat
      sperm during epididymal transit by inducing the elimination of zinc and affecting
      the amount of free sulphydryl groups in the sperm flagella.

PMID- 15169923
TI  - Alternative splicing of the human luteal LH receptor during luteolysis and
      maternal recognition of pregnancy.
AB  - Deletion of exon 10 of the human LH receptor impairs LH but not hCG action. Other
      splice variants of the LH receptor impair both LH and hCG action in other
      species. We hypothesized that alternatively spliced LH receptors are involved in
      luteolysis and luteal rescue with hCG in women. mRNA was extracted from human
      luteinized granulosa cells and from corpora lutea from across the luteal phase
      and after luteal rescue in vivo with exogenous hCG. Splice variants were detected
      by RT-PCR using carefully designed primer pairs. Products were visualized on
      agarose gels, extracted, purified and sequenced. Three splice variants of the
      human LH receptor were detected and characterized. These demonstrate a region of
      multiple splicing between exons 8 and 11 of the receptor. A naturally occurring
      splice variant with exon 10 alone removed was not identified. There was no
      obvious change in the pattern of splice variants across the luteal phase in the
      presence or absence of hCG. These data do not support the hypothesis that
      qualitative changes in LH receptor splicing have a role in luteolysis or that a
      naturally occurring LH receptor lacking exon 10 has a role in maternal
      recognition of pregnancy.

PMID- 15169924
TI  - PharmGKB update: II. CYP3A5, cytochrome P450, family 3, subfamily A, polypeptide
      5.

PMID- 15169925
TI  - PharmGKB update: III. Genetic variants of SLC22A1, solute carrier family 22
      (organic cation transporter), member 1.

PMID- 15169926
TI  - Aging biology and geriatric clinical pharmacology.
AB  - Population aging evokes doomsday economic and sociological prognostication,
      despite a minority of older people suffering significant dependency and the
      potential for advances in therapeutics of age-related disease and primary aging.
      Biological aging processes are linked mechanistically to altered drug handling,
      altered physiological reserve, and pharmacodynamic responses. Parenteral loading
      doses need only be adjusted for body weight as volumes of distribution are little
      changed, whereas oral loading doses in some cases may require reduction to
      account for age-related increases in bioavailability. Age-related reduction of
      hepatic blood flow and hepatocyte mass and primary aging changes in hepatic
      sinusoidal endothelium with effects on drug transfer and oxygen delivery reduce
      hepatic drug clearance. Primary renal aging is evident, although renal clearance
      reduction in older people is predominantly disease-related and is poorly
      estimated by standard methods. The geriatric dosing axiom, "start low and go
      slow" is based on pharmacokinetic considerations and concern for adverse drug
      reactions, not from clinical trial data. In the absence of generalizable dosage
      guidelines, individualization via effect titration is required. Altered
      pharmacodynamics are well documented in the cardiovascular system, with changes
      in the autonomic system, autacoid receptors, drug receptors, and endothelial
      function to modify baseline cardiovascular tone and responses to stimuli such as
      postural change and feeding. Adverse drug reactions and polypharmacy represent
      major linkages to avoidable morbidity and mortality. This, combined with a
      deficient therapeutic evidence base, suggests that extrapolation of risk-benefit
      ratios from younger adults to geriatric populations is not necessarily valid.
      Even so, therapeutic advances generally may convert healthy longevity from an
      asset of fortunate individuals into a general social benefit.

PMID- 15169927
TI  - Anthracyclines: molecular advances and pharmacologic developments in antitumor
      activity and cardiotoxicity.
AB  - The clinical use of anthracyclines like doxorubicin and daunorubicin can be
      viewed as a sort of double-edged sword. On the one hand, anthracyclines play an
      undisputed key role in the treatment of many neoplastic diseases; on the other
      hand, chronic administration of anthracyclines induces cardiomyopathy and
      congestive heart failure usually refractory to common medications. Second
      generation analogs like epirubicin or idarubicin exhibit improvements in their
      therapeutic index, but the risk of inducing cardiomyopathy is not abated. It is
      because of their janus behavior (activity in tumors vis-a-vis toxicity in
      cardiomyocytes) that anthracyclines continue to attract the interest of
      preclinical and clinical investigations despite their longer-than-40-year record
      of longevity. Here we review recent progresses that may serve as a framework for
      reappraising the activity and toxicity of anthracyclines on basic and clinical
      pharmacology grounds. We review 1) new aspects of anthracycline-induced DNA
      damage in cancer cells; 2) the role of iron and free radicals as causative
      factors of apoptosis or other forms of cardiac damage; 3) molecular mechanisms of
      cardiotoxic synergism between anthracyclines and other anticancer agents; 4) the
      pharmacologic rationale and clinical recommendations for using cardioprotectants
      while not interfering with tumor response; 5) the development of tumor-targeted
      anthracycline formulations; and 6) the designing of third-generation analogs and
      their assessment in preclinical or clinical settings. An overview of these issues
      confirms that anthracyclines remain "evergreen" drugs with broad clinical
      indications but have still an improvable therapeutic index.

PMID- 15169928
TI  - Neuromedin U and its receptors: structure, function, and physiological roles.
AB  - Neuromedin U (NmU) is a structurally highly conserved neuropeptide. It is
      ubiquitously distributed, with highest levels found in the gastrointestinal tract
      and pituitary. Originally isolated from porcine spinal cord, it has since been
      isolated and sequenced from several species. Amino acid alignment of NmU from
      different species reveals a high level of conservation, and particular features
      within its structure are important for bioactivity. Specifically, the C terminus,
      including a terminal asparagine-linked amidation, is essential for activity. The
      conservation of NmU across a wide range of species indicates a strong
      evolutionary pressure to conserve this peptide and points to its physiological
      significance. Despite this, the precise physiological and indeed
      pathophysiological roles of NmU have remained elusive. NmU was first isolated
      based on its ability to contract rat uterine smooth-muscle (hence the suffix "U")
      and has since been implicated in the regulation of smooth-muscle contraction,
      blood pressure and local blood flow, ion transport in the gut, stress responses,
      cancer, gastric acid secretion, pronociception, and feeding behavior. Two G
      protein-coupled receptors for NmU have recently been cloned. These receptors are
      widespread throughout the body but have differential distributions suggesting
      diverse but specific roles for the receptor subtypes. Here we detail the
      isolation and characterization of NmU, describe the discovery, cloning,
      distribution, and structure of its two receptors, and outline its possible roles
      in both physiology and pathophysiology. Ultimately the development of receptor
      specific ligands and the generation of animals in which the receptors have been
      selectively knocked out will hopefully reveal the true extent of the biological
      roles of NmU and suggest novel therapeutic indications for selective activation
      or blockade of either of its receptors.

PMID- 15169929
TI  - The significance of vasoactive intestinal peptide in immunomodulation.
AB  - First identified by Said and Mutt some 30 years ago, the vasoactive intestinal
      peptide (VIP) was originally isolated as a vasodilator peptide. Subsequently, its
      biochemistry was elucidated, and within the 1st decade, their signature features
      as a neuropeptide became consolidated. It did not take long for these insights to
      permeate the field of immunology, out of which surprising new attributes for VIP
      were found in the last years. VIP is rapidly transforming into something more
      than a mere hormone. In evolving scientifically from a hormone to a novel agent
      for modifying immune function and possibly a cytokine-like molecule, VIP research
      has engaged many physiologists, molecular biologists, biochemists,
      endocrinologists, and pharmacologists and it is a paradigm to explore mutual
      interactions between neural and neuroendocrine links in health and disease. The
      aim of this review is firstly to update our knowledge of the cellular and
      molecular events relevant to VIP function on the immune system and secondly to
      gather together recent data that support its role as a type 2 cytokine.
      Recognition of the central functions VIP plays in cellular processes is focusing
      our attention on this "very important peptide" as exciting new candidates for
      therapeutic intervention and drug development.

PMID- 15169930
TI  - Liver-enriched transcription factors in liver function and development. Part II:
      the C/EBPs and D site-binding protein in cell cycle control, carcinogenesis,
      circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene
      regulation.
AB  - In the first part of our review (see Pharmacol Rev 2002;54:129-158), we discussed
      the basic principles of gene transcription and the complex interactions within
      the network of hepatocyte nuclear factors, coactivators, ligands, and
      corepressors in targeted liver-specific gene expression. Now we summarize the
      role of basic region/leucine zipper protein family members and particularly the
      albumin D site-binding protein (DBP) and the CAAT/enhancer-binding proteins
      (C/EBPs) for their importance in liver-specific gene expression and their role in
      liver function and development. Specifically, regulatory networks and molecular
      interactions were examined in detail, and the experimental findings summarized in
      this review point to pivotal roles of DBP and C/EBPs in cell cycle control,
      carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and
      liver-specific gene regulation. These regulatory proteins are therefore of great
      importance in liver physiology, liver disease, and liver development.
      Furthermore, interpretation of the vast data generated by novel genomic platform
      technologies requires a thorough understanding of regulatory networks and
      particularly the hierarchies that govern transcription and translation of
      proteins as well as intracellular protein modifications. Thus, this review aims
      to stimulate discussions on directions of future research and particularly the
      identification of molecular targets for pharmacological intervention of liver
      disease.

PMID- 15169931
TI  - Loss of plastidic lysophosphatidic acid acyltransferase causes embryo-lethality
      in Arabidopsis.
AB  - Phosphatidic acid is a key intermediate for chloroplast membrane lipid
      biosynthesis. De novo phosphatidic acid biosynthesis in plants occurs in two
      steps: first the acylation of the sn-1 position of glycerol-3-phosphate giving
      rise to lysophosphatidic acid; second, the acylation of the sn-2 position of
      lysophosphatidic acid to form phosphatidic acid. The second step is catalyzed by
      a lysophosphatidic acid acyltransferase (LPAAT). Here we describe the
      identification of the ATS2 gene of Arabidopsis encoding the plastidic isoform of
      this enzyme. Introduction of the ATS2 cDNA into E. coli JC 201, which is
      temperature-sensitive and carries a mutation in its LPAAT gene plsC, restored
      this mutant to nearly wild type growth at high temperature. A green-fluorescent
      protein fusion with ATS2 localized to the chloroplast. Disruption of the ATS2
      gene of Arabidopsis by T-DNA insertion caused embryo lethality. The development
      of the embryos was arrested at the globular stage concomitant with a transient
      increase in ATS2 gene expression. Apparently, plastidic LPAAT is essential for
      embryo development in Arabidopsis during the transition from the globular to the
      heart stage when chloroplasts begin to form.

PMID- 15169932
TI  - Pollen development and tube growth are affected in the symbiotic mutant of Lotus
      japonicus, crinkle.
AB  - The symbiotic mutant of Lotus japonicus, crinkle (crk), exhibits abnormal
      nodulation and other alterations in the root hairs, trichomes, and seedpods.
      Defective nodulation in crk mutant is due to the arrested infection thread growth
      from the epidermis into the cortex. Here, we describe that crk is also affected
      in male fertility that causes the production of small pods with few seeds. Under
      in vitro conditions, pollen germination and tube growth were markedly reduced in
      the crk mutant. A swollen tip phenotype with disorganized filamentous actin (F
      actin) was observed in the mutant pollen tubes after prolonged in vitro culture.
      During pollen development, the striking difference noted in the mutant was the
      small size of the microspores that remained spherical. Histological examination
      of ovule development, as well as outcrosses of the mutant as female to wild type
      as male, showed no evidence of abnormality in the female gametophyte development.
      Based on these findings, the Crk gene, aside from its role in the infection
      process during nodulation, is also involved in male gametophyte development and
      function. Therefore, this gene represents a connection between nodule symbiosis,
      polar tip growth, and other plant developmental processes.

PMID- 15169933
TI  - Overexpression of the barley aquaporin HvPIP2;1 increases internal CO(2)
      conductance and CO(2) assimilation in the leaves of transgenic rice plants.
AB  - The internal conductance for CO(2) diffusion (g(i)) and CO(2) assimilation rate
      were measured and the related anatomical characteristics were investigated in
      transgenic rice leaves that overexpressed barley aquaporin HvPIP2;1. This study
      was performed to test the hypothesis that aquaporin facilitates CO(2) diffusion
      within leaves. The g(i) value was estimated for intact leaves by concurrent
      measurements of gas exchange and carbon isotope ratio. The leaves of the
      transgenic rice plants that expressed the highest levels of Aq-anti-HvPIP2;1
      showed a 40% increase in g(i) as compared to g(i) in the leaves of wild-type rice
      plants. The increase in g(i) was accompanied by a 14% increase in CO(2)
      assimilation rate and a 27% increase in stomatal conductance (g(s)). The
      transgenic plants that had low levels of Aq-anti-HvPIP2;1 showed decreases in
      g(i) and CO(2) assimilation rate. In the plants with high levels of Aq-anti
      HvPIP2;1, mesophyll cell size decreased and the cell walls of the epidermis and
      mesophyll cells thickened, indicating that the leaves had become xeromorphic.
      Although such anatomical changes could partially offset the increase in g(i) by
      the aquaporin, the increase in aquaporin content overcame such adverse effects.

PMID- 15169935
TI  - Secretion in unicellular marine phytoplankton: demonstration of regulated
      exocytosis in Phaeocystis globosa.
AB  - Almost half of the global photosynthetic activity is carried out in the ocean.
      During blooms, Phaeocystis can fix CO(2) at rates up to 40 g C m(-2) month(-1).
      Most of this carbon is released as polysaccharides. However, the cellular
      mechanism whereby this huge amount of organic material is exported into the
      seawater remains unknown. A vaguely defined process of "exudation" is believed
      responsible for the release of these biopolymers. Here we report the first
      demonstration that Phaeocystis globosa does not "exude", but secretes microscopic
      gels. Secretion is stimulated by blue light (lambda = 470+/-20 nm), and it is
      transduced by a characteristic intracellular Ca(2+) signal that precedes
      degranulation. The polysaccharides that form the matrix of these gels remain in
      condensed phase while stored in secretory vesicles. Upon exocytosis, the
      exopolymer matrix undergoes a characteristic phase transition accompanied by
      extensive swelling resulting in the formation of microscopic hydrated gels. Owing
      to their tangled topology, once released into the seawater, the polymers that
      make these gels can reptate (axially diffuse), interpenetrate neighboring gels,
      and anneal them together forming massive mucilage accumulations that are
      characteristic of Phaeocystis blooms. These gel masses can supply a rich source
      of microbial substrates, disperse in the seawater, and/or eventually sediment to
      the ocean floor.

PMID- 15169934
TI  - Role of apoplastic ascorbate and hydrogen peroxide in the control of cell growth
      in pine hypocotyls.
AB  - The growth cessation of plant axis has been related with the formation of
      diphenyl bridges among the pectic components of the cell wall caused by the
      action of apoplastic peroxidases using hydrogen peroxide as electron acceptor.
      The formation of diphenyl bridges is prevented by the presence of ascorbate in
      the apoplastic fluid which acts as a hydrogen peroxide scavenger. The current
      work focuses on the role of the apoplastic ascorbate and hydrogen peroxide in the
      cell growth. The addition of hydrogen peroxide caused an inhibition of the auxin
      induced growth as well as a significant decrease in the cell wall creep induced
      by acid-pH solutions. The hydrogen peroxide content in apoplastic fluid increased
      with the hypocotyl age and along the hypocotyl axis of 10-day-old pine seedlings,
      as the growth capacity decreased. On the other hand, the ascorbate content in the
      apoplastic fluid decreased with the hypocotyl age and along the hypocotyl axis of
      10-day-old seedlings. A very significant correlation between the hydrogen
      peroxide apoplastic level and the growth rate as well as between the
      ascorbate/hydrogen peroxide molar ratio and the growth rate of hypocotyls have
      been found suggesting that the redox state is the main factor controlling the
      cell wall stiffening mechanism and thus growth in pine hypocotyls.

PMID- 15169936
TI  - Accumulation of 1,3-beta-D-glucans, in response to aluminum and cytosolic calcium
      in Triticum aestivum.
AB  - One of the most rapid responses to aluminum (Al) stress in plants is enhanced
      synthesis and deposition of 1,3-beta-D-glucans (callose) in root tips.
      Ironically, Al-induced synthesis and deposition of callose occurs in vivo,
      despite evidence from in vitro systems that suggests that Al is a powerful
      inhibitor of 1,3-beta-D-glucan synthase. We set out to test the hypothesis that
      an Al-induced increase in the activity of free calcium in the cytoplasm
      ([Ca(2+)](cyt)) is the trigger for enhanced synthesis of callose in in vivo
      systems, an effect that would not be observed in in vitro systems. Root tips of
      an Al-sensitive cultivar of Triticum aestivum were treated with Al (0-100 microM)
      or the Ca ionophore A23187 (0-3 micro M) for 3-24 h, and the effects on
      [Ca(2+)](cyt) and synthesis of callose were measured using confocal laser
      scanning microscopy. Treatment with Al induced a rapid increase in both
      [Ca(2+)](cyt) (4.7-fold) and synthesis of callose (30-fold). Treatment with the
      Ca ionophore, A23187, also elicited an increase in [Ca(2+)](cyt) (6.6-fold).
      Despite a greater increase in [Ca(2+)](cyt) in the presence of A23187, this
      increase was accompanied by a smaller increase in callose deposition (11-fold)
      than was observed in the presence of Al. These data suggest that an increase in
      [Ca(2+)](cyt) is not the only factor modulating increases in callose synthesis
      and deposition in the presence of Al.

PMID- 15169937
TI  - A novel rice PR10 protein, RSOsPR10, specifically induced in roots by biotic and
      abiotic stresses, possibly via the jasmonic acid signaling pathway.
AB  - Plant roots have important roles not only in absorption of water and nutrients,
      but also in stress tolerance such as desiccation, salt, and low temperature. We
      have investigated stress-response proteins from rice roots using 2-dimensional
      polyacrylamide-gel electrophoresis and found a rice protein, RO-292, which was
      induced specifically in roots when 2-week-old rice seedlings were subjected to
      salt and drought stress. The full-length RO-292 cDNA was cloned, and was
      determined to encode a protein of 160 amino acid residues (16.9 kDa, pI 4.74).
      The deduced amino acid sequence showed high similarity to known rice PR10
      proteins, OsPR10a/PBZ1 and OsPR10b. RO-292 mRNA accumulated rapidly upon drought,
      NaCl, jasmonic acid and probenazole, but not by exposure to low temperature or by
      abscisic acid and salicylic acid. The RO-292 gene was also up-regulated by
      infection with rice blast fungus. Interestingly, induction was observed almost
      exclusively in roots, thus we named the gene RSOsPR10 (root specific rice PR10).
      The present results indicate that RSOsPR10 is a novel rice PR10 protein, which is
      rapidly induced in roots by salt, drought stresses and blast fungus infection
      possibly through activation of the jasmonic acid signaling pathway, but not the
      abscisic acid and salicylic acid signaling pathway.

PMID- 15169938
TI  - Temporal and spatial distribution of pectin epitopes in differentiating anthers
      and microspores of fertile and sterile sugar beet.
AB  - We studied the possible involvement of several pectin epitopes in anther
      differentiation and microsporogenesis in fertile and cytoplasmically male sterile
      sugar beets. The spatial and temporal distribution of five structural motifs were
      traced with a panel of monoclonal antibodies in six stages: premeiosis, meiotic
      prophase, young and mature tetrads, young and expanding microspores. The
      composition of the walls of sporogenous cells and meiocytes differed than that in
      the tapetum, as evidenced by the presence of alpha-Fuc(1-->2)-beta-Gal and alpha
      (1-->5)-L-Ara epitopes binding CCRC-M1 and LM6 antibodies. At meiotic prophase,
      the meiocyte walls were additionally marked by the appearance of poorly methyl
      esterified domains of homogalacturonan and of (1-->4)-beta-Gal residues, detected
      by JIM5 and LM5. Some constituents of the meiocyte wall which reacted with JIM5
      and JIM7 persisted on the surface of the special callose sheath during tetrad
      development. In newly formed primexine and exine layers of tetrads and
      microspores, epitopes that were bound by JIM5, JIM7 and LM5 were abundant. No
      differences in the deposition or relative abundance of pectins were found between
      fertile and sterile anthers until microspore release from the callose. Later, at
      the time of abortion, sterile microspores had much larger amounts of epitopes
      detected by JIM5 than their fertile counterparts.

PMID- 15169939
TI  - Microtubules of guard cells are light sensitive.
AB  - Guard cells of stomata are characterized by ordered bundles of microtubules
      radiating from the ventral side toward the dorsal side of the cylindrical cell.
      It was suggested that microtubules play a role in directing the radial
      arrangement of the cellulose micro-fibrils of guard cells. However, the role of
      microtubules in daily cycles of opening and closing of stomata is not clear. The
      organization of microtubules in guard cells of Commelina communis leaves was
      studied by analysis of three-dimensional immunofluorescent images. It was found
      that while guard cell microtubules in the epidermis of leaves incubated in the
      light were organized in parallel, straight and dense bundles, in the dark they
      were less straight and oriented randomly near the stomatal pore. The effect of
      blue and red light on the organization of guard cell microtubules resembled the
      effects of white light and dark respectively. When stomata were induced to open
      in the dark with fusicoccin, microtubules remained in the dark configuration.
      Furthermore, when incubated in the light, guard cell microtubules were more
      resistant to oryzalin. Similarly, microtubules of Arabidopsis guard cells,
      expressing green fluorescent protein-tubulin alpha 6, were disorganized in the
      dark, but were organized in parallel arrays in the presence of white light. The
      dynamics of microtubule rearrangement upon transfer of intact leaves from dark to
      light was followed in single stomata, showing that an arrangement of microtubules
      typical for light conditions was obtained after 1 h in the light. Our data
      suggest that microtubule organization in guard cells is responsive to light
      signals.

PMID- 15169940
TI  - Aluminum targets elongating cells by reducing cell wall extensibility in wheat
      roots.
AB  - Phytotoxicity of aluminum is characterized by a rapid inhibition of root
      elongation at micromolar concentrations, however, the mechanisms primarily
      responsible for this response are not well understood. We investigated the effect
      of Al on the viscosity and elasticity parameters of root cell wall by a creep
      extension analysis in two cultivars of wheat (Triticum aestivum L.) differing in
      Al resistance. The root elongation and both viscous and elastic extensibility of
      cell wall of the root apices were hardly affected by the exposure to 10 microM Al
      in an Al-resistant cultivar, Atlas 66. However, similar exposure rapidly
      inhibited root elongation in an Al-sensitive cultivar, Scout 66 and this was
      associated with a time-dependent accumulation of Al in the root tissues with more
      than 77% residing in the cell wall. Al caused a significant decrease in both the
      viscous and elastic extensibility of cell wall of the root apices of Scout 66.
      The "break load" of the root apex of Scout 66 was also decreased by Al. However,
      neither the viscosity nor elasticity of the cell wall was affected by in vitro Al
      treatment. Furthermore, pre-treatment of seedlings with Al in conditions where
      root elongation was slow (i.e. low temperature) did not affect the subsequent
      elongation of roots in a 0 Al treatment at room temperature. These results
      suggest that the Al-dependent changes in the cell wall viscosity and elasticity
      are involved in the inhibition of root growth. Furthermore, for Al to reduce cell
      wall extensibility it must interact with the cell walls of actively elongating
      cells.

PMID- 15169941
TI  - Identification and molecular characterization of myosin gene family in Oryza
      sativa genome.
AB  - Myosins play an important role in various developmental processes in plants. We
      have identified 14 myosin genes in rice (Oryza sativa cv. Nipponbare) genome
      using sequence information available in public databases. Phylogenetic analysis
      of these sequences with other plant and non-plant myosins revealed that two of
      the predicted sequences belonged to class VIII and the others to class XI. All of
      these genes were distributed on seven chromosomes in the rice genome. Domain
      searches on these sequences indicated that a typical rice myosin consisted of
      Myosin_N, head domain, neck (IQ motifs), tail, and dilute (DIL) domain. Based on
      the sequence information obtained from predicted myosins, we isolated and
      sequenced two full-length cDNAs, OsMyoVIIIA and OsMyoXIE, representing each of
      the two classes of myosins. These two cDNAs isolated from different organs
      existed in isoforms due to differential splicing and showed minor differences
      from the predicted myosin in exon organization. Out of 14 myosin genes 11 were
      expressed in three major organs: leaves, panicles, and roots, among which three
      myosins exhibited different expression levels. On the other hand, three of the
      total myosin sequences showed organ-specific expression. The existence of
      different myosin genes and their isoforms in different organs or tissues
      indicates the diversity of myosin functions in rice.

PMID- 15169942
TI  - The cotton GhNHX1 gene encoding a novel putative tonoplast Na(+)/H(+) antiporter
      plays an important role in salt stress.
AB  - A cDNA clone was isolated from cotton (Gossypium hirsutum) cDNA library and
      characterized with regard to its sequence, regulation in response to salt stress
      and functions in yeast mutants and transgenic tobacco plants. The clone,
      designated as GhNHX1, contains 2485 nucleotides with an open reading frame of
      1629 nucleotides, and the deduced amino acid sequence showed high identities with
      other plant vacuolar-type Na(+)/H(+) antiporters. Northern blot analysis
      indicated that the mRNA accumulation of GhNHX1 was strongly induced by salt
      stress and abscisic acid in cotton seedlings. The expression of GhNHX1 in yeast
      Na(+)/H(+) antiporter mutant showed function complementation. The transgenic
      tobacco plants overexpressing GhNHX1 also had higher salt tolerance than the wild
      type plants. The salt-induced mRNA level of GhNHX1 was 3 and 7 times higher in
      the salt-tolerant cotton cultivar ZM3 than those in the salt-sensitive cotton
      cultivars ZMS17 and ZMS12, respectively. Together, these results suggest that the
      products of the novel gene, GhNHX1, function as a tonoplast Na(+)/H(+) antiporter
      and play an important role in salt tolerance of cotton.

PMID- 15169943
TI  - Phosphorylation of plasma membrane aquaporin regulates temperature-dependent
      opening of tulip petals.
AB  - The opening and closing of tulip petals was reproduced in the dark by changing
      the temperature from 5 degrees C to 20 degrees C for opening and 20 degrees C to
      5 degrees C for closing. The opening process was accompanied by (3)H(2)O
      transport through the stem from the incubation medium to the petals. A Ca(2+)
      channel blocker and a Ca(2+)-chelator inhibited petal opening and (3)H(2)O
      transport. Several proteins in the isolated plasma membrane fraction were
      phosphorylated in the presence of 25 micro M Ca(2+) at 20 degrees C. The 31-kDa
      protein that was phosphorylated, was suggested immunologically as the putative
      plasma membrane aquaporin (PM-AQP). This phosphorylated PM-AQP clearly reacted
      with the anti-phospho-Ser. In-gel assay revealed the presence of a 45-kDa Ca(2+)
      dependent protein kinase in the isolated plasma membrane. Phosphorylation of the
      putative PM-AQP was thought to activate the water channel composed of PM-AQP.
      Dephosphorylation of the phosphorylated PM-AQP was also observed during petal
      closing at 5 degrees C, suggesting the inactivation of the water channel.

PMID- 15169944
TI  - Induction of a crassulacean acid-like metabolism in the C(4) succulent plant,
      Portulaca oleracea L: study of enzymes involved in carbon fixation and
      carbohydrate metabolism.
AB  - The C(4) succulent plant Portulaca oleracea shifts its photosynthetic metabolism
      to crassulacean acid metabolism (CAM) after 23 d of withholding water. This is
      accounted by diurnal acid fluctuation, net nocturnal but not day CO(2) uptake and
      drastic changes in phosphoenolpyruvate carboxylase (PEPC) kinetic and regulatory
      properties [Lara et al. (2003) Photosynth: Res. 77: 241]. The goal of the present
      work was to characterize the CAM activity in leaves of P. oleracea during water
      stress through the study of enzymes involved in carbon fixation and carbohydrate
      metabolism. After drought stress, a general decrease in the photosynthetic
      metabolism, as accounted by the decrease in the net CO(2) fixation and in the
      activity of enzymes such as ribulose-1,5-bisphosphate carboxylase/oxygenase,
      PEPC, pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxykinase and NAD
      malic enzyme was observed. We also found changes in the day/night activities and
      level of immunoreactive protein of some of these enzymes which were correlated to
      night CO(2) fixation, as occurs under CAM metabolism. Based on the results
      obtained, including those from in situ immunolocalization studies, we propose a
      scheme for the possible CO(2) fixation pathways used by P. oleracea under
      conditions of sufficient and limiting water supply.

PMID- 15169945
TI  - Ca(2+) and calmodulin modulate DNA-binding activity of maize heat shock
      transcription factor in vitro.
AB  - DNA-binding activity of a maize heat shock transcription factor (HSF) was induced
      by heat shock of a whole cell extract at 44 degrees C. Addition of the calcium
      ion chelator EGTA reduced the binding of the HSF to heat shock element (HSE) in
      vitro. Re-addition of CaCl(2) to the sample pretreated with EGTA restored the
      ability of the HSF to bind to DNA. DNA-binding activity of the HSF was also
      induced by directly adding CaCl(2) to a whole cell extract at non-heat-shock
      temperature, but not by MgCl(2). During HS at 44 degrees C, calmodulin (CaM)
      antagonists chlorpromazine (CPZ) and N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W7) inhibited DNA-binding activity of the HSF in a
      concentration-dependent manner, but N-(6-aminohexyl)-1-naphthalenesulfonamide
      (W5), an inactive structural analogue of W7, did not. Addition of antiserum
      specific to CaM reduced the binding of the HSF to HSE. Re-addition of CaM to the
      sample pretreated with antiserum could restore the binding activity of the HSF.
      DNA-binding activity of the HSF was promoted by directly adding CaM to a whole
      cell extract at 44 degrees C, but not by BSA. Moreover, at non-heat-shock
      temperature, DNA-binding activity of the HSF was also induced by directly adding
      CaM to a whole cell extract, but not by BSA. Our observations further confirm the
      role of Ca(2+) in activation of the HSF in plant and provide the first example of
      the role of CaM in regulation of DNA-binding activity of the HSF. These results
      suggest that Ca(2+) and CaM are involved in HSP gene expression likely through
      regulating the activity of the HSF.

PMID- 15169946
TI  - Changes in the thermal dissipation and the electron flow in the water-water cycle
      in rice grown under conditions of physiologically low temperature.
AB  - Effects of low temperature on chlorophyll (Chl) fluorescence, gas exchange rate,
      the amounts of xanthophyll cycle pigments (Xp) and the activities of several
      antioxidant enzymes were examined in the 8th leaf of two rice (Oryza sativa L.)
      cultivars (japonica and indica types) and rbcS antisense rice. All plants were
      grown hydroponically at 25/20 degrees C (day/night), and then exposed to 20/17
      degrees C (day/night) after full expansion of the 8th leaf, or exposed to either
      20/17 degrees C or 15/13 degrees C (day/night) during the expansion of the 8th
      leaf. All plants exposed to low temperatures showed a decrease in CO(2)
      assimilation rate without photoinhibition, and increases in the fraction of
      thermal dissipation in PSII, and in the electron flux through the water-water
      cycle (WWC) were observed. Although the increase of thermal dissipation was
      associated with increases in the ratio of carotenoids to Chl, the ratio of Xp to
      carotenoids and the de-epoxidation state of Xp, the increase of the electron flux
      of WWC was not accompanied by an increase in the activities of antioxidant
      enzymes. Such photoprotective responses did not differ between during and after
      full expansion of the leaf, and did not differ among the three genotypes.
      Quantitative analyses on the dissipation of excess light energy showed that
      thermal dissipation makes a larger contribution than WWC. Thus, although low
      temperature led to a decrease in CO(2) assimilation, rice potentially coped with
      the excess light energy by increasing the thermal dissipation and the electron
      flux of WWC under low temperature irrespective of leaf development and genotypes.

PMID- 15169947
TI  - Characterization of circadian-associated APRR3 pseudo-response regulator
      belonging to the APRR1/TOC1 quintet in Arabidopsis thaliana.
AB  - In higher plants, there are wide ranges of biological processes that are
      controlled through the circadian clock. In this connection, we have been
      characterizing a small family of proteins, designated as ARABIDOPSIS PSEUDO
      RESPONSE REGULATORS (APRR1, APRR3, APRR5, APRR7, and APRR9), among which APRR1 is
      identical to TOC1 (TIMING OF CAB EXPRESSION1) that is believed to be a component
      of the central oscillator. Through previous genetic studies, several lines of
      evidence have already been provided to support the view that, not only
      APRR1/TOC1, but also other APRR1/TOC1 quintet members are important for a better
      understanding of the molecular links between circadian rhythm, control of
      flowering time, and also photomorphogenesis. However, the least characterized one
      was APRR3 in that no genetic study has been conducted to see if APRR3 also plays
      an important role in the circadian-associated biological events. Here we show
      that APRR3-overexpressing transgenic plants (APRR3-ox) exhibited: (i). a
      phenotype of longer period (and/or delayed phase) of rhythms of certain circadian
      controlled genes under continuous white light, (ii). a phenotype of late
      flowering under long-day photoperiod conditions, (iii). a phenotype of hypo
      sensitiveness to red light during early photomorphogenesis of de-etiolated
      seedlings, supporting the current idea as to the APRR1/TOC1 quintet described
      above.

PMID- 15169948
TI  - Photosynthetic electron transport controls expression of the high light inducible
      gene in the cyanobacterium Synechococcus elongatus strain PCC 7942.
AB  - The hliA gene of Synechococcus, encoding a photoprotective high light inducible
      polypeptide, is up-regulated by high light (HL) or low intensity blue/UV-A light
      (BL). hliA expression was found to be up-regulated by KCN in low light (LL) (but
      not in the dark), and up-regulation in HL, BL, and LL (with KCN) was inhibited by
      2,5-dibromo-3-methyl-6-isopropyl-benzoquinone. A working hypothesis is proposed
      whereby up-regulation is in response to the reduced state of cytochrome b(6)f or
      a carrier beyond in photosynthesis. Modest up-regulation occurs in LL by
      treatment with 3-(3,4-dichlorophenyl)-1,1-dimethylurea, but this is related to
      effects on hliA mRNA stability rather than on transcription.

PMID- 15169949
TI  - Identification of active site residues in mevalonate diphosphate decarboxylase:
      implications for a family of phosphotransferases.
AB  - A combination of sequence homology analyses of mevalonate diphosphate
      decarboxylase (MDD) proteins and structural information for MDD leads to the
      hypothesis that Asp 302 and Lys 18 are active site residues in MDD. These
      residues were mutated to replace acidic/basic side chains and the mutant proteins
      were isolated and characterized. Binding and competitive displacement studies
      using trinitrophenyl-ATP, a fluorescent analog of substrate ATP, indicate that
      these mutant enzymes (D302A, D302N, K18M) retain the ability to
      stoichiometrically bind nucleotide triphosphates at the active site. These
      observations suggest the structural integrity of the mutant MDD proteins. The
      functional importance of mutated residues was evaluated by kinetic analysis. The
      10(3) and 10(5)-fold decreases in k(cat) observed for the Asp 302 mutants (D302N
      and D302A, respectively) support assignment of a crucial catalytic role to Asp
      302. A 30-fold decrease in activity and a 16-fold inflation of the K(m) for ATP
      is documented for the K18M mutant, indicating that Lys 18 influences the active
      site but is not crucial for reaction chemistry. Demonstration of the influence of
      conserved aspartate 302 appears to represent the first documentation of the
      functional importance of a residue in the MDD catalytic site and affords insight
      into phosphotransferase reactions catalyzed by a variety of enzymes in the
      galactokinase, homoserine kinase, mevalonate kinase, phosphom-evalonate kinase
      (GHMP kinase) family.

PMID- 15169950
TI  - Zinc-dependent dimerization of the folding catalyst, protein disulfide isomerase.
AB  - Protein disulfide isomerase (PDI), an essential folding catalyst and chaperone of
      the endoplasmic reticulum (ER), has four structural domains (a-b-b'-a'-) of
      approximately equal size. Each domain has sequence or structural homology with
      thioredoxin. Sedimentation equilibrium and velocity experiments show that PDI is
      an elongated monomer (axial ratio 5.7), suggesting that the four thioredoxin
      domains are extended. In the presence of physiological levels (<1 mM) of Zn(2+)
      and other thiophilic divalent cations such as Cd(2+) and Hg(2+), PDI forms a
      stable dimer that aggregates into much larger oligomeric forms with time. The
      dimer is also elongated (axial ratio 7.1). Oligomerization involves the
      interaction of Zn(2+) with the cysteines of PDI. PDI has active sites in the N
      terminal (a) and C-terminal (a')thioredoxin domains, each with two cysteines
      (CGHC). Two other cysteines are found in one of the internal domains (b').
      Cysteine to serine mutations show that Zn(2+)-dependent dimerization occurs
      predominantly by bridging an active site cysteine from either one of the active
      sites with one of the cysteines in the internal domain (b'). The dimer
      incorporates two atoms of Zn(2+) and exhibits 50% of the isomerase activity of
      PDI. At longer times and higher PDI concentrations, the dimer forms oligomers and
      aggregates of high molecular weight (>600 kDa). Because of a very high
      concentration of PDI in the ER, its interaction with divalent ions could play a
      role in regulating the effective concentration of these metal ions, protecting
      against metal toxicity, or affecting the activity of other (ER) proteins that use
      Zn(2+) as a cofactor.

PMID- 15169952
TI  - The role of aromaticity, exposed surface, and dipole moment in determining
      protein aggregation rates.
AB  - The mechanisms by which peptides and proteins form ordered aggregates are not
      well understood. Here we focus on the physicochemical properties of amino acids
      that favor ordered aggregation and suggest a parameter-free model that is able to
      predict the change of aggregation rates over a large set of natural sequences.
      Furthermore, the results of the parameter-free model correlate well with the
      aggregation propensities of a set of peptides designed by computer simulations.

PMID- 15169951
TI  - Facile chemical synthesis and equilibrium unfolding properties of CopG.
AB  - The 45-amino acid polypeptide chain of the homodimeric transcriptional repressor,
      CopG, was chemically synthesized by stepwise solid phase peptide synthesis (SPPS)
      using a protocol based on Boc-chemistry. The product obtained from the synthesis
      was readily purified by reversed-phase HPLC to give a good overall yield (21% by
      weight). Moreover, the synthetic CopG constructs prepared in this work folded
      into three-dimensional structures similar to the wild-type protein prepared using
      conventional recombinant methods as judged by far UV-CD spectroscopy. A
      fluorescent CopG analog, (Y39W)CopG, was also designed and chemically synthesized
      to facilitate biophysical studies of CopG's protein folding and assembly
      reaction. The guanidinium chloride-induced equilibrium unfolding properties of
      the wild-type CopG and (Y39W)CopG constructs in this work were characterized and
      used to develop a model for CopG's equilibrium unfolding reaction. Our results
      indicate that CopG's folding and assembly reaction is well modeled by a two-state
      process involving folded dimer and unfolded monomer. Using this model, DeltaG(f)
      and m-values of -13.42 +/- 0.04 kcal/mole dimer and 1.92 +/- 0.01 kcal/(mole M)
      were calculated for CopG.

PMID- 15169953
TI  - The C-terminal domain of full-length E. coli SSB is disordered even when bound to
      DNA.
AB  - The crystal structure of full-length homotetrameric single-stranded DNA (ssDNA)
      binding protein from Escherichia coli (SSB) has been determined to 3.3 A
      resolution and reveals that the entire C-terminal domain is disordered even in
      the presence of ssDNA. To our knowledge, this is the first experimental evidence
      that the C-terminal domain of SSB may be inherently disordered. The N-terminal
      DNA-binding domain of the protein is well ordered and is virtually
      indistinguishable from the previously determined structure of the chymotryptic
      fragment of SSB (SSBc) in complex with ssDNA. The absence of observable
      interactions with the core protein and the crystal packing of SSB together
      suggest that the disordered C-terminal domains likely extend laterally away from
      the DNA- binding domains, which may facilitate interactions with components of
      the replication machinery in vivo. The structure also reveals the conservation of
      molecular contacts between successive tetramers mediated by the L(45) loops as
      seen in two other crystal forms of SSBc, suggesting a possible functional
      relevance of this interaction.

PMID- 15169954
TI  - Insulin forms amyloid in a strain-dependent manner: an FT-IR spectroscopic study.
AB  - The presence of 20% (v/v) ethanol triggers growth of insulin amyloid with
      distinct infrared spectroscopic features, compared with the fibrils obtained
      under ambient conditions. Here we report that the two insulin amyloid types
      behave in the prion strain-like manner regarding seeding specificity and ability
      of the self-propagating conformational template to overrule unfavorable
      environmental factors and maintain the initial folding pattern. The type of the
      original seed has been shown to prevail over cosolvent effects and determines
      spectral position and width of the amide I' infrared band of the heterogeneously
      seeded amyloid. These findings imply that "strains" may be a common generic trait
      of amyloids.

PMID- 15169955
TI  - Crystal structure of rat alpha-parvalbumin at 1.05 Angstrom resolution.
AB  - The crystal structure of rat alpha-parvalbumin has been determined at 1.05
      Angstrom resolution, using synchrotron data collected at Advanced Photon Source
      beamline 19-ID. After refinement with SHELX, employing anisotropic displacement
      parameters and riding hydrogen atoms, R = 0.132 and R(free) = 0.162. The average
      coordinate estimated standard deviations are 0.021 Angstrom and 0.038 Angstrom
      for backbone atoms and side-chain atoms, respectively. Besides providing a more
      precise view of the alpha-isoform than previously available, these data permit
      comparison with the 0.91 Angstrom structure determined for pike beta-parvalbumin.
      Visualization of the anisotropic displacement parameters as thermal ellipsoids
      yields insight into the atomic motion within the Ca(2+)-binding sites. The
      asymmetric unit includes three parvalbumin (PV) molecules. Interestingly, the EF
      site in one displays uncharacteristic flexibility. The ellipsoids for Asp-92 are
      particularly large and non-spherical, and the shape of the Ca(2+) ellipsoid
      implies significant vibrational motion perpendicular to the plane defined by the
      four y and z ligands. The relative dearth of crystal-packing interactions in this
      site suggests that the heightened flexibility may be the result of diminished
      intermolecular contacts. The implication is that, by impeding conformational
      mobility, crystal-packing forces may cause serious overestimation of EF-hand
      rigidity. The high quality of the data permitted 11 residues to be modeled in
      alternative side-chain conformations, including the two core residues, Ile-97 and
      Leu-105. The discrete disorder observed for Ile-97 may have functional
      ramifications, providing a mechanism for communicating binding status between the
      CD and EF binding loops and between the PV metal ion-binding domain and the N
      terminal AB region.

PMID- 15169956
TI  - Affinity transfer by CDR grafting on a nonimmunoglobulin scaffold.
AB  - Neocarzinostatin (NCS) is a small "all beta" protein displaying the same overall
      fold as immunoglobulins. This protein possesses a well-defined hydrophobic core
      and two loops structurally equivalent to the CDR1 and CDR3 of immunoglobulins.
      NCS is the most studied member of the enediynechromoprotein family, and is
      clinically used as an antitumoral agent. NCS has promise as a drug delivery
      vehicle if new binding specificities could be conferred on its protein scaffold.
      Previous studies have shown that the binding specificity of the crevasse can be
      extended to compounds completely unrelated to the natural enediyne chromophore
      family. We show here that it is possible to introduce new interaction capacities
      to obtain a protein useful for drug targeting by modifying the immunoglobulin CDR
      like loops. We transferred the CDR3 of the VHH chain of camel antilysozyme
      immunoglobulin to the equivalent site in the corresponding loop of
      neocarzinostatin. We then evaluated the stability of the resulting structure and
      its affinity for lysozyme. The engineered NCS-CDR3 presents a structure similar
      to that of the wild-type NCS, and is stable and efficiently produced. ELISA, ITC,
      and SPR measurements demonstrated that the new NCS-CDR3 specifically bound
      lysozyme.

PMID- 15169960
TI  - Dry granular flows can generate surface features resembling those seen in Martian
      gullies.
AB  - Over the past decade or more, contradictory evidence of Martian climate,
      indicating that surface temperatures seldom if ever approach the melting point of
      water at midlatitudes, and geomorphic features, consistent with liquid flows at
      these same latitudes, have proven difficult to reconcile. In this article, we
      demonstrate that several features of liquid-erosional flows can be produced by
      dry granular materials when individual particle settling is slower than
      characteristic debris flow speeds. Since the gravitational acceleration on Mars
      is about one-third that on Earth, and since particle settling speeds scale with
      gravity, we propose that some (although perhaps not all) Martian geomorphological
      features attributed to liquid flows may in fact be associated with dry granular
      flows in the presence of reduced gravity.

PMID- 15169958
TI  - Frizzled6 controls hair patterning in mice.
AB  - Hair whorls and other macroscopic hair patterns are found in a variety of
      mammalian species, including humans. We show here that Frizzled6 (Fz6), one
      member of a large family of integral membrane Wnt receptors, controls macroscopic
      hair patterning in the mouse. Fz6 is expressed in the skin and hair follicles,
      and targeted deletion of the Fz6 gene produces stereotyped whorls on the hind
      feet, variable whorls and tufts on the head, and misorientation of hairs on the
      torso. Embryo chimera experiments imply that Fz6 acts locally to control or
      propagate the macroscopic hair pattern and that epithelial cells rather than
      melanocytes are the source of Fz6-dependent signaling. The Fz6 phenotype strongly
      resembles the wing-hair and bristle patterning defects observed in Drosophila
      frizzled mutants. These data imply that hair patterning in mammals uses a Fz
      dependent tissue polarity system similar to the one that patterns the Drosophila
      cuticle.

PMID- 15169959
TI  - The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix
      associated element.
AB  - The protein CTCF plays an essential role in the action of a widely distributed
      class of vertebrate enhancer-blocking insulators, of which the first example was
      found in a DNA sequence element, HS4, at the 5' end of the chicken beta-globin
      locus. HS4 contains a binding site for CTCF that is necessary and sufficient for
      insulator action. Purification of CTCF has revealed that it interacts with
      proteins involved in subnuclear architecture, notably nucleophosmin, a 38-kDa
      nucleolar phosphoprotein that is concentrated in nuclear matrix preparations. In
      this report we show that both CTCF and the HS4 insulator element are incorporated
      in the matrix; HS4 incorporation depends on the presence of an intact CTCF
      binding site. However the DNA sequence in the neighborhood of HS4 is not like
      that of canonical matrix attachment regions, and its incorporation into the
      matrix fraction is not sensitive to ribonuclease, suggesting that the insulator
      is a distinct matrix-associated element.

PMID- 15169957
TI  - Long-term combined beneficial effects of physical training and metabolic
      treatment on atherosclerosis in hypercholesterolemic mice.
AB  - The pathogenic mechanisms by which physical exercise influences atherosclerotic
      lesion formation remain poorly understood. Because vigorous physical training
      increases oxidative stress, this study tested the hypothesis that graduated and
      moderate physical exercise together with metabolic intervention (l-arginine and
      antioxidants) may contribute to increased vascular protection. Exercise training
      in mice was induced by graduated swimming. In hypercholesterolemic male mice on
      an atherogenic high-cholesterol diet, graduated and moderate exercise lowered
      plasma cholesterol and decreased atherosclerotic lesions compared with sedentary
      control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C
      added to the drinking water) and l-arginine (6% in drinking water)
      supplementation to exercising hypercholesterolemic mice further and
      synergistically reduced atherosclerosis compared with untreated exercised mice.
      Arterial oxidation-specific epitopes and systemic oxidative stress were reduced
      by metabolic intervention. Graduated chronic exercise elicited an increase in
      production of nitric oxide through increased endothelial nitric oxide synthase
      expression and ameliorated scavenger activities. Thus, metabolic intervention
      with l-arginine and antioxidants together with graduated and moderate exercise
      training reduce atherosclerotic lesion formation.

PMID- 15169962
TI  - Keeping medicine and science together.

PMID- 15169961
TI  - Egg viability and worker policing in honey bees.
AB  - In many species of social Hymenoptera, unmated workers can lay eggs that will
      produce males by parthenogenesis. Nevertheless, in queenright honey bee colonies
      (Apis mellifera), worker reproduction is low. One possible mechanism for this
      difference is worker policing, the removal of worker-laid eggs by other workers.
      This behavior can evolve in species in which queens are multiply mated, where
      workers are more closely related to the sons of their mother than those of their
      sisters. Another possible mechanism of the low level of worker reproduction is
      worker-laid eggs being less viable than queen-laid eggs. We show that this
      difference in quality is the case for honey bees.

PMID- 15169963
TI  - Biological roles of alpha-fetoprotein during pregnancy and perinatal development.
AB  - The use of alpha-fetoprotein (AFP) as a serum marker in cancer actually predates
      its employment in the detection of congenital defects; however, the latter use of
      AFP as a fetal defect marker has propelled its clinical utilization. Although the
      serum-marker capacity of AFP has long been exploited, less is known of the
      biological activities of this oncofetal protein during fetal and perinatal
      development. In the present review, the biological activities of AFP are
      discussed in light of this glycoprotein's presence in various biological fluid
      compartments: embryonic and fetal tissues, serum, urine, and reproductive fluids.
      After a review of the histochemical detection of AFP in various cells and tissues
      during development, AFP concentrations within various biological fluids were
      discussed in the context of gestational age and anatomic location. Discussion
      follows concerning the relationships and roles of AFP in developmental events
      such as erthyropoiesis, histogenesis/organogenesis, and ligand binding and in
      developmental disorders such as hypothyroidism, folate deficiencies, and acquired
      immunodeficiency disorder (AIDS). Based on its association with so many types of
      birth defects, malformations, and congenital anomalies, AFP can be viewed as a
      molecular "troubleshooter" until signal transduction pathways are established
      during pregnancy and prenatal development. The review concludes with a discussion
      of the place of AFP in the rapidly expanding field of proteomics.

PMID- 15169965
TI  - Iodine toxicity and its amelioration.
AB  - Iodine (I) toxicity is rare in animals and humans, but nuclear explosions that
      give off radioactive I and excessive stable I ingestion in parts of the world
      where seaweed is consumed represent specialized I toxicity concerns. Chronic
      overconsumption of I reduces organic binding of I by the thyroid gland, which
      results in hypothyroidism and goiter. Bromine can replace I on position 5 of both
      T(3) and T(4) with no loss of thyroid hormone activity. Avian work has also
      demonstrated that oral bromide salts can reverse the malaise and growth
      depressions caused by high doses of I (as KI) added as supplements to the diet.
      Newborn infants by virtue of having immature thyroid glands are most susceptible
      to I toxicity, whether of stable or radioactive origin. For the latter, the 1986
      Chernobyl nuclear accident in Belarus has provided evidence that KI blockage
      therapy for exposed individuals 18 years of age and younger is effective in
      minimizing the development of thyroid cancer. Whether bromide therapy has a place
      in I toxicity situations remains to be determined.

PMID- 15169964
TI  - Nutrition and infectious diseases in developing countries and problems of
      acquired immunodeficiency syndrome.
AB  - Infectious diseases are the major causes of death and morbidity in underdeveloped
      countries, particularly in children. Increasing evidence suggests that
      malnutrition-both Protein-Energy type Malnutrition (PEM) and essential
      micronutrient (vitamins, trace minerals, essential amino acids, polyunsaturated
      fatty acids) type-is the underlying reason for increased susceptibility to
      infections. On the other hand, certain infectious diseases also cause
      malnutrition, which results in a vicious cycle. Before its viral origin was
      known, acquired immunodeficiency syndrome (AIDS) had been termed the thin disease
      because cachexia was AIDS' main clinical manifestation. The relationship between
      infection and malnutrition is well documented in the literature. Our experience
      supports this. Preventive and therapeutic measures are suggested.

PMID- 15169967
TI  - Role of fatty acid composition in the development of metabolic disorders in
      sucrose-induced obese rats.
AB  - Fatty acids have been shown to be involved in the development of insulin
      resistance associated with obesity. We used sucrose loading in rats to analyze
      changes in fatty acid composition in the progression of obesity and the related
      metabolic disorder. Although rats fed a sucrose diet for 4 weeks had body weights
      similar to those of control animals, their visceral fat pads were significantly
      larger, and serum triglyceride levels were higher; however, neither plasma
      glucose nor insulin levels were significantly higher. After 20 weeks of sucrose
      loading, body weight and visceral and subcutaneous fat pads had increased
      significantly compared with those in control rats. Moreover, plasma glucose,
      insulin, and triglyceride levels were significantly higher. An analysis of
      individual fatty acid components in the blood and peripheral tissues demonstrated
      phase- and tissue-dependent changes. After 20 weeks of sucrose loading,
      palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9), the major components of
      monounsaturated fatty acid, showed a ubiquitous increase in plasma and all
      tissues analyzed. In contrast, linoleic acid (18:2 n-6) and arachidonic acid
      (20:4 n-6), the major components of polyunsaturated fatty acid in the n-6 family,
      decreased in plasma and all tissues analyzed. After 4 weeks of sucrose loading,
      these changes in fatty acid composition were observed only in the liver and
      plasma and not in fat and muscle. This led us to conclude that elevation of
      plasma glucose and insulin develop at the late phase of sucrose-induced obesity,
      when changes in fatty acid composition appear in fat and muscle. Furthermore,
      changes in fatty acid composition in liver seen after 4 weeks of sucrose loading,
      when increases in neither plasma glucose nor insulin were detected, suggest that
      liver may be the initial site of fatty acid imbalance and that aberrations in
      hepatic fatty acid composition may lead to fatty acid imbalances in other
      tissues.

PMID- 15169966
TI  - Expression of lung uncoupling protein-2 mRNA is modulated developmentally and by
      caloric intake.
AB  - Lung expresses a high concentration of uncoupling protein-2 (UCP-2) mRNA, but
      neither its pulmonary regulation nor function is known. We measured lung UCP-2
      mRNA expression in two animal models: in neonatal rats when both the metabolic
      rate, as measured by oxygen consumption, and levels of serum free fatty acids
      (FFAs) increase and in adult mice during decreased food intake, when levels of
      serum FFAs increase but the metabolic rate decreases. In rat lung, the
      concentration of UCP-2 mRNA was low and unchanged during late gestation,
      increased approximately twofold within 6 hrs after birth, and, compared with late
      gestation, remained approximately threefold higher from day 1 to adulthood. The
      early postnatal rise in the lung UCP-2 mRNA concentration was partially blocked
      by an antithyroid drug and was increased by treatment with triiodothyronine.
      Unlike lung, heart UCP-2 mRNA levels were lower during adulthood than at day 15.
      In adult mice, lung UCP-2 mRNA concentrations increased approximately fivefold
      within 12 hrs of 67% calorie restriction (CR), remained elevated during 2 weeks
      of CR, fell to control levels within 24 hrs of refeeding (CR-RF), and positively
      correlated with serum FFA concentrations. Heart UCP-2 expression during CR and CR
      RF was similar to that of lung; liver UCP-2 mRNA levels were slightly lower
      during CR and returned to control levels during CR-RF. These data suggest that
      the regulation of UCP-2 is at least partly tissue-specific and that, in the adult
      mouse, lung UCP-2 is regulated not by oxygen consumption but by FFAs. Moreover,
      lung UCP-2 mRNA levels in mice fed ad libitum was increased by the
      intraperitoneal administration of Intralipid, a 20% fat emulsion. On the basis of
      these data in adult mice, together with the findings of others that levels of
      FFAs increase by 2 hrs after birth, we propose lung UCP-2 is regulated by FFA.

PMID- 15169968
TI  - Senescent B lymphopoiesis is balanced in suppressive homeostasis: decrease in
      interleukin-7 and transforming growth factor-beta levels in stromal cells of
      senescence-accelerated mice.
AB  - The suppression of the B cell population during senescence has been considered to
      be due to the suppression of interleukin-7 (IL-7) production and responsiveness
      to IL-7; however, the upregulation of transforming growth factor-beta (TGF-beta)
      was found to contribute to B cell suppression. To investigate the mechanism of
      this suppression based on the interrelationship between IL-7 and TGF-beta during
      senescence, senescence-accelerated mice (SAMs), the mouse model of aging, were
      used in this study to elucidate the mechanisms of B lymphopoietic suppression
      during aging. Similar to regular senescent mice, SAMs showed a decrease in the
      number of IL-7-responding B cell progenitors (i.e., colony-forming unit pre-B
      [CFU-pre-B] cells in the femoral bone marrow [BM]). A co-culture system of B
      lymphocytes and stromal cells that the authors established showed a significantly
      lower number of CFU-pre-B cells harvested when BM cells were co-cultured with
      senescent stromal cells than when they were co-cultured with young stromal cells.
      Interestingly, cells harvested from a senescent stroma and those from the control
      culture without stromal cells were higher in number than those harvested from a
      young stroma, thereby implying that an altered senescent stromal cell is unable
      to maintain self-renewal of the stem cell compartment. Because TGF-beta is
      supposed to suppress the proliferative capacity of pro-B/pre-B cells, we added a
      neutralizing anti-TGF-beta antibody to the co-culture system with a pro-B/pre-B
      cell-rich population to determine whether such suppression may be rescued.
      However, unexpectedly, any rescue was not observed and the number of CFU-pre-B
      cells remained unchanged when BM cells were co-cultured with senescent stromal
      cells compared with the co-culture with young stromal cells, which essentially
      showed an increase in the number of CFU-pre-B cells (P < 0.001 in 5 microg/ml).
      Furthermore, TGF-beta protein level in the supernatant of cultured senescent
      stroma cells was evaluated by enzyme-linked immunoabsorbent assay, but
      surprisingly, it was found that TGF-beta concentration was significantly lower
      than that of cultured young stromal cells. Thus, TGF-beta activity was assumed to
      decline particularly in a senescent stroma, which means a distinct difference
      between the senescent suppression of B lymphopoiesis and secondary B
      lymphocytopenia. Concerning proliferative signaling, on the other hand, the level
      of IL-7 gene expression in cells from freshly isolated BM decreased significantly
      with age. Therefore, the acceleration of proliferative signaling and the
      deceleration of suppressive signaling may both be altered and weakened in a
      senescent stroma (i.e., homeosuppression).

PMID- 15169969
TI  - Altered activity of signaling pathways in diaphragm and tibialis anterior muscle
      of dystrophic mice.
AB  - Duchenne muscular dystrophy is a musculoskeletal disease caused by mutations in
      the dystrophin gene. The purpose of this study was to use the mouse model of
      muscular dystrophy (mdx) to determine if the progression of the dystrophic
      phenotype in the diaphragm (costal) versus limb skeletal muscle (tibialis
      anterior) is associated with specific changes in extracellular regulated kinase
      (ERK1/2), p70 S6 kinase (p70(S6k)), or p38 signaling pathways. The studies
      detected that consistent with an earlier dystrophic phenotype, phosphorylation of
      p70(S6k) is elevated by 40% in the diaphragm with no change in limb muscle. In
      addition, phosphorylation of p38 kinase was decreased by 33% in the mdx diaphragm
      muscle. Levels of ERK1/2 as well as phosphorylation states were elevated in the
      diaphragm and limb muscle of mdx mice compared with age-matched control muscles.
      These results indicate that distinct signaling pathways are differentially
      activated in skeletal muscle of mdx mice. The specificity of these responses,
      particularly in the diaphragm, provides insight for potential targets for
      blunting the progression of the muscular dystrophy phenotype.

PMID- 15169971
TI  - Combined treatment with vessel dilator and kaliuretic hormone in persons with
      congestive heart failure.
AB  - Vessel dilator and kaliuretic hormone, two cardiovascular peptide hormones,
      enhance urine flow 2- to 13-fold and 4-fold, respectively, in persons with class
      III New York Heart Association congestive heart failure (CHF). The natriuresis
      and diuresis secondary to vessel dilator and kaliuretic hormone are not blunted
      as are atrial natriuretic peptide and brain natriuretic peptide effects in
      persons with CHF compared with healthy individuals. The present investigation
      determined if the two peptide hormones that do not have blunted effects in
      persons with CHF may have added beneficial effects when given simultaneously to
      individuals with class III CHF. Together with each at 100 ng/kg of body weight
      per minute, vessel dilator and kaliuretic hormone increased urine flow rate 3.5
      fold (P < 0.05) compared with their 60-min baseline and control CHF subjects'
      urine flow rates. Combined, they enhanced the excretion rate of sodium a maximum
      of 3.6-fold (P < 0.05) with 2.5- and 2-fold enhancement 2 and 3 hrs after
      infusion. These data indicate that vessel dilator and kaliuretic hormone have
      diuretic and natriuretic effects when used in combination, but these effects are
      not additive over their individual effects in persons with CHF.

PMID- 15169970
TI  - Compensatory growth of adipose tissue after partial lipectomy: involvement of
      serum factors.
AB  - The regulation of body weight/fat was studied by investigating mechanisms for
      compensatory adipose tissue growth after removal of bilateral epididymal fat pads
      from male adult Wistar rats. Food intake during the first 4 weeks and energy
      expenditure on Days 8-10 postsurgery were not different between lipectomized and
      sham operated rats. During Days 29-31 post surgery, a small (2.4%) but
      significant (P < 0.05) increase in heat production per metabolic body size was
      detected in lipectomized as compared with sham operated rats. The carcass
      composition of lipectomized and sham operated rats was not significantly
      different 16 weeks after surgery. The compensatory growth was fat pad-specific:
      mesenteric, retroperitoneal, and inguinal fat pads, but not perirenal fat pads,
      were heavier in lipectomized rats than in sham operated rats as early as 4 weeks
      postsurgery. Examination of fat cell size distribution in the compensating pads
      indicated a shift toward larger cells in retroperitoneal fat, but not in inguinal
      fat of lipectomized as compared with sham operated rats. Serum from lipectomized
      rats, but not media conditioned by exposure to retroperitoneal fat pads from
      lipectomized rats, stimulated proliferation of preadipocytes in vitro more than
      that from sham operated rats. Thus, compensatory adipose tissue growth after
      lipectomy may be mediated, in part, by blood-borne factors that are derived from
      tissues other than adipose tissue.

PMID- 15169972
TI  - Differential effects of low-density lipoprotein and chylomicron remnants on lipid
      accumulation in human macrophages.
AB  - The effects of low-density lipoprotein (LDL) and chylomicron remnants on lipid
      accumulation in human monocyte-derived macrophages (HMDMs) and in macrophages
      derived from the human monocyte cell line THP-1 were compared. The HMDMs or THP-1
      macrophages were incubated with LDL, oxidized LDL (oxLDL), chylomicron remnant
      like particles (CMR-LPs), or oxidized CMR-LPs (oxCMR-LPs), and the amount and
      type of lipid accumulated were determined. As expected, the lipid content of both
      cell types was increased markedly by oxLDL but not LDL, and this was due to a
      rise in cholesterol, cholesteryl ester (CE), and triacylglycerol (TG) levels. In
      contrast, both CMR-LPs and oxCMR-LPs caused a considerable increase in cellular
      lipid in HMDMs and THP-1 macrophages, but in this case there was a greater rise
      in the TG than in the cholesterol or CE content. Lipid accumulation in response
      to oxLDL, CMR-LPs, and oxCMR-LPs was prevented by the ACAT inhibitor CI976 in
      HMDMs but not in THP-1 macrophages, where TG levels remained markedly elevated.
      The rate of incorporation of [(3)H]oleate into CE and TG in THP-1 macrophages was
      increased by oxLDL, CMR-LPs, and oxCMR-LPs, but incorporation into TG was
      increased to a greater extent with CMR-LPs and oxCMR-LPs compared with oxLDL.
      These results demonstrate that both CMR-LPs and oxCMR-LPs cause lipid
      accumulation in human macrophages comparable to that seen with oxLDL and that
      oxidation of the remnant particles does not enhance this effect. They also
      demonstrate that a greater proportion of the lipid accumulated in response to CMR
      LPs compared with oxLDL is TG rather than cholesterol or CE and that this is
      associated with a higher rate of TG synthesis. This study, therefore, provides
      further evidence to suggest that chylomicron remnants have a role in foam cell
      formation that is distinct from that of oxLDL.

PMID- 15169974
TI  - Oxidative damage to DNA of ovarian surface epithelial cells affected by
      ovulation: carcinogenic implication and chemoprevention.
AB  - The majority of cancers of the ovary are thought to originate from a surface
      epithelial cell perturbed by ovulation. Outgrowth of a follicle destined to
      ovulate brings it into apposition with the ovarian epithelium. Ovarian surface
      cells are consequently exposed, within a limited diffusion radius, to
      inflammatory agents and reactive oxidants generated during periovulatory
      processes. Cells that overlie the formative site of follicular rupture suffer
      irreparable damages and undergo apoptosis. Potentially mutagenic 8-oxoguanine
      modifications were detected in (surviving) cells circumjacent to postovulatory
      ovine and human follicles. It is conceivable that clonal expansion of a cell with
      unrepaired DNA, but not committed to death, could be an initiating factor in the
      etiology of malignancy, insofar as proliferative ovulatory wound-repair responses
      may propagate mutations. Since the prognosis for ovarian cancer patients with
      invasive disease is so poor, and early detection has proven elusive, it is
      imperative that prospective methods of chemo-prevention be explored. Ovulation
      induced oxidative base damages to the ovarian epithelium of ewes were prevented
      by vitamin E. Oxoguanine adducts persisted and CA-125 (a phenotype of metaplastic
      transformation) was expressed in cultures of cells that were distressed by
      ovulation in which p53 synthesis was inhibited. Vitamin E negated this reaction.
      Ovarian cyclicity and fertility were not altered in vitamin-treated ewes. A
      prophylactic benefit of a supplemental antioxidant is suggested in "ovulating"
      individuals designated at risk (e.g., due to a tumor suppressor malfunction) for
      the development of ovarian cancer.

PMID- 15169973
TI  - Inflammation and ischemia: macrophages activated by fibronectin fragments enhance
      the survival of injured cardiac myocytes.
AB  - Proteolytic enzymes, released early in the course of an inflammatory response,
      hydrolyze fibronectin, producing fragments of the parent molecule that alter
      monocyte phenotype and migratory behavior. Here we test the hypothesis that
      macrophages, stimulated by the dominant 110-120 kd fibronectin fragments (FNf),
      as are found in lymphatic fluid draining sites of cardiac ischemia-reperfusion
      injury, produce factors that promote the survival of injured parenchymal cells.
      Rat splenic macrophages stimulated in vitro with purified FNf produced soluble
      factors that protected hypoxic rat cardiac myocytes from death by apoptosis.
      Addition of blocking antibodies specific for tumor necrosis factor-alpha(TNF
      alpha), fibroblast growth factor-1 (FGF-1), insulin-like growth factor I (IGF-I),
      and leukemia inhibitory factor (LIF) partly reduced the protection against
      apoptosis provided to hypoxic cardiac myocytes by cell-free culture supernatants
      from FNf-stimulated macrophages. Complete blockade of this protection was
      achieved by a combination of antibodies specific for FGF-1, IGF-I, and LIF.
      Stimulation of human monocyte-derived macrophages in vitro with FNf significantly
      increased their output of TNF-alpha, FGF-1, IGF-I, and LIF. These results suggest
      that tissue degradation products, released in the early hours of an inflammatory
      response, stimulate tissue-infiltrating macrophages to protect injured but still
      viable parenchymal cells from death by apoptosis.

PMID- 15169976
TI  - Mycotoxins in root extracts of American and Asian ginseng bind estrogen receptors
      alpha and beta.
AB  - The estrogenic activity of ginseng has been the subject of conflicting reports.
      Cell proliferation, induction of estrogen-responsive genes, and isolated cases of
      adverse reactions such as postmenopausal vaginal bleeding and gynecomastia have
      been reported after ginseng treatment. Other studies report antiproliferative
      effects with no induction of estrogen-responsive genes. We developed estrogen
      receptor (ER) alpha and ER alpha competitive binding assays using recombinant
      receptors and [(3)H]-17 alpha-estradiol to detect phytoestrogens in extracts of
      Asian ginseng root (Panax ginseng C. A. Meyer) and American ginseng root (Panax
      quinquefolius L.). Root extracts contained substances that bound both receptor
      isoforms. These substances had a two to three times greater affinity for ER
      alpha. Significantly higher binding was found in methanol extracts than in hot
      water extracts. Subsequent analysis of the extracts revealed significant ER
      binding attributable to zearalenone, the estrogenic mycotoxin produced by several
      Fusarium species. The ER showed no binding affinity for Rb1 and Rg1, the major
      ginsenosides found in P. quinquefolius and P. ginseng, respectively. Thus,
      ginseng extraction methods, plant species tested, and mycotoxin contaminants may
      help to explain the disparate literature reports. The prevalence and health
      significance of fungal contamination in herbal products used for medicinal
      purposes should be further investigated.

PMID- 15169977
TI  - CME: the "third phase" of a doctor's education.

PMID- 15169975
TI  - Myocardial oxidative stress and toxicity induced by acute ethanol exposure in
      mice.
AB  - Alcoholic cardiomyopathy has been known for a long time, but there is little
      mechanistic insight into this important clinical problem. The present study was
      undertaken using a mouse model to test the hypothesis that alcohol exposure
      induces cardiac injury through induction of oxidative stress. Adult female Friend
      Virius B-type (FVB) mice were treated with ethanol by gavage at a dose of 5 g/kg.
      Six hours after the treatment, ethanol-induced myocardial injury was observed, as
      indicated by a significant increase in serum creatine phosphokinase activity, a
      common biomarker of myocardial injury, and myocardial ultrastructural
      alterations, predominantly mitochondrial swelling and cristae disarray and
      reduction in numbers. The myocardial injury was associated with a significant
      increase in the myocardial lipid peroxidation, determined by measuring
      thiobarbituric acid reactive substances (TBARS), and a significant increase in
      protein oxidation as measured by a protein carbonyl content assay. Acute alcohol
      exposure decreased glutathione (GSH) content in the heart, more so in the
      mitochondria than in the cytosol. These alcohol-induced myocardial injuries and
      oxidative stresses were all significantly inhibited by supplementation with N
      acetyl-L-cysteine (NAC) prior to alcohol exposure. However, NAC did not affect
      the rise in blood alcohol concentrations following alcohol exposure. This study
      thus demonstrates that acute alcohol administration causes myocardial injury
      through, at least in part, the induction of oxidative stress. A rapid decrease in
      mitochondrial GSH content may be partially responsible for the observed
      mitochondrial damage.

PMID- 15169978
TI  - Enter Alimta: a new generation antifolate.

PMID- 15169979
TI  - The miracle of Iressa.

PMID- 15169980
TI  - T-cell large granular lymphocyte leukemia and related disorders.
AB  - T-cell large granular lymphocyte (LGL) leukemia is a clonal proliferation of
      cytotoxic T cells, which causes neutropenia, anemia, and/or thrombocytopenia.
      This condition is often associated with autoimmune disorders, especially
      rheumatoid arthritis, and other lymphoproliferative disorders. The diagnosis is
      suggested by flow cytometry demonstrating an expansion of CD8(+)CD57(+) T cells
      and is confirmed by T-cell receptor gene rearrangement studies. Mounting evidence
      suggests that LGL leukemia is a disorder of dysregulation of apoptosis through
      abnormalities in the Fas/Fas ligand pathway. In most patients, this is an
      indolent disorder, and significant improvement of cytopenias can be achieved with
      immunosuppressive agents such as steroids, methotrexate, cyclophosphamide, and
      cyclosporin A. This review provides a concise, up-to-date summary of LGL leukemia
      and the related, more aggressive, malignancies of cytotoxic T cells and natural
      killer cells.

PMID- 15169981
TI  - Optimizing treatment of chronic myeloid leukemia: a rational approach.
AB  - Imatinib mesylate, a novel, molecularly targeted agent for the treatment of
      chronic myeloid leukemia (CML), has expanded the management options for this
      disease and provided a paradigm for the treatment of other cancers. Imatinib is a
      potent, specific inhibitor of BCR-ABL, the constitutively active protein tyrosine
      kinase critical to the pathogenesis of CML. A randomized, phase III comparison of
      imatinib with interferon-alfa plus cytarabine as initial treatment for newly
      diagnosed chronic-phase CML, which demonstrated significantly higher rates of
      disease response with less toxicity, better quality of life, and a significantly
      longer progression-free survival time, provided the most persuasive data
      supporting a major role for imatinib. Currently, allogeneic stem cell
      transplantation is the only treatment modality with long-term data demonstrating
      curative potential in CML. An option for less than half of CML patients and
      associated with substantial morbidity and mortality, transplantation may still be
      appropriate initial therapy for certain patients. Busulfan and hydroxyurea have
      no demonstrable effect on disease natural history. The interferon-plus-cytarabine
      combination can induce durable cytogenetic remissions and was previously the CML
      pharmacotherapy standard of care, but it is often poorly tolerated. Imatinib is
      now indicated as first-line therapy for CML in all phases.

PMID- 15169982
TI  - Indications for imatinib mesylate therapy and clinical management.
AB  - Imatinib mesylate (Gleevec), Glivec, formerly STI571; Novartis Pharma AG; Basel,
      Switzerland) is a rationally-designed, molecularly-specific oral anticancer agent
      that selectively inhibits several protein tyrosine kinases central to the
      pathogenesis of human cancer. It has demonstrated remarkable clinical efficacy in
      patients with chronic myeloid leukemia and malignant gastrointestinal stromal
      tumors. Treatment with imatinib is generally well tolerated, and the risk for
      severe adverse effects is low. Adverse effects most commonly include mild-to
      moderate edema, nausea and vomiting, diarrhea, muscle cramps, and cutaneous
      reactions. Hepatic transaminase level elevations and myelosuppression occur less
      frequently and resolve with interruption of imatinib therapy. In general, the
      incidence and severity of adverse effects tend to correlate with imatinib dose
      and, in chronic myeloid leukemia patients, the phase of disease; but, patient age
      and other factors are also associated with some types of reactions. With prompt
      and appropriate intervention, adverse effects in imatinib-treated patients have
      proven to be manageable across the spectrum of severity, and they seldom require
      permanent cessation of therapy. Dose reduction is not usually necessary, and
      reduction to subtherapeutic levels is not recommended.

PMID- 15169983
TI  - New chemotherapeutic advances in pancreatic, colorectal, and gastric cancers.
AB  - Pancreatic, gastric, and colorectal cancers are major causes of morbidity and
      mortality worldwide. When curative surgical resection is not an option, these
      malignancies tend to respond very poorly to chemotherapy and carry a dismal
      prognosis. There is, therefore, an urgent need for novel treatment strategies for
      these cancers. Great strides have been made in colon cancer treatment with the
      recent introduction of several novel agents, including capecitabine, irinotecan,
      and oxaliplatin either alone or in combination regimens. Treatment of advanced
      colon cancer, however, remains essentially palliative, and treatment-related
      toxicity remains a significant problem. The treatment of advanced gastric and
      pancreatic cancer has also seen the introduction of new agents, such as
      gemcitabine and irinotecan; however, the impact of these agents on survival has
      been small, and toxicity continues to be a major obstacle. The search for new
      chemotherapeutic agents and treatment strategies will need to focus on improving
      outcomes and safety and tolerability profiles. To date, several new agents have
      shown promise, including pemetrexed, G17DT, bevacizumab, and other targeted
      agents. Further research into their optimal use either alone or in combination
      regimens should be a priority.

PMID- 15169984
TI  - Intermittent androgen deprivation therapy for prostate cancer.
AB  - Androgen deprivation therapy for prostate cancer is associated with several
      complications, including loss of libido, hot flashes, night sweats, psychological
      stress, osteoporosis, anemia, fatigue, loss of muscle mass, glucose intolerance,
      and changes in lipid profile. The natural history of prostate cancer while on
      such therapy is the attainment of an incurable androgen-independent state. Early
      diagnosis by prostate-specific antigen screening, longer life expectancies, and a
      penchant for immediate therapy pose a problem where clinicians have to balance
      the potential benefits of early hormonal therapy with the risks of development of
      these metabolic and psychological complications. Intermittent androgen
      deprivation offers clinicians a prospect to improve quality of life in patients
      with prostate cancer by harmonizing the benefits of androgen ablation with a
      reduction in treatment-related side effects and expenditure. In this review we
      discuss the challenges and opportunities of this mode of therapy and shed light
      on some of the underlying molecular mechanisms.

PMID- 15169985
TI  - Advances in chemoprevention of head and neck cancer.
AB  - Head and neck squamous cell carcinoma is a devastating disease with a poor
      outcome in advanced stages, accounting for approximately 3% of all malignancies,
      with an estimated 37200 new cases and 11000 deaths annually in the U.S. Second
      primary tumors are estimated to occur at an annual rate of 3%-10% and are
      significant threats to long-term survivors. Chemoprevention is an appealing
      strategy, and its success has been demonstrated in breast cancer and familial
      adenomatous polyposis. High-dose retinoids have been shown to be active against
      oral premalignant lesions and in prevention of second primary tumors in the head
      and neck. New targets include the epidermal growth factor receptor,
      cyclooxygenase-2, and other molecular targets. Challenges in future head and neck
      cancer chemoprevention investigations include achieving long-lasting efficacy
      with retinoids and/or new agents, and determining the optimal dose and duration
      of therapy while maintaining acceptable toxicities.

PMID- 15169986
TI  - NMR spectroscopy and pediatric brain tumors.
AB  - Proton nuclear magnetic resonance spectroscopy ((1)H-NMRS) is a noninvasive in
      vivo technique that utilizes conventional MR imaging hardware to obtain
      biochemical information from a discrete volume of tissue after suppression of the
      water signal. MR spectroscopy coupled with conventional MR imaging allows
      correlation of structural changes with biochemical processes in tissues by
      measuring specific metabolites present in brain tissue. NMRS is commonly used in
      the evaluation of patients with brain tumors. This article reviews the basic
      principles of spectroscopy and its use in evaluating pediatric patients with
      brain tumors.

PMID- 15169988
TI  - Cancer of unknown primary: changing approaches. A multidisciplinary case
      presentation from the Joan Karnell cancer center of pennsylvania hospital.
AB  - Cancer of unknown primary is a common clinical syndrome, accounting for 2%-5% of
      cancer patients. A representative case is presented. This heterogenous group of
      disorders includes entities such as poorly differentiated carcinoma of unknown
      primary, adenocarcinoma of unknown primary, neuroendocrine carcinoma of unknown
      primary, squamous cell carcinoma of unknown primary, poorly differentiated (not
      otherwise specified) cancer of unknown primary, and melanoma of unknown primary.
      It is crucial to identify those treatment-responsive presentations of unknown
      primary with the greatest potential for long-term survival. This discussion
      emphasizes newer approaches to the diagnosis and treatment of unknown primary
      cancer, including advances in pathology with immunoperoxidase and molecular
      genetic techniques, positron emission tomography, and published chemotherapeutic
      trials. With the increased sophistication of pathologic and radiologic
      techniques, the frequency of unknown primary cancers will likely continue to
      decline. Further, as newer and more targeted therapies for specific types of
      cancer are identified, the previously held nihilism regarding the search for and
      identification of the primary may become less supportable.

PMID- 15169987
TI  - Safety and convenience of a 15-minute infusion of zoledronic acid.
AB  - Skeletal morbidity, including hypercalcemia of malignancy (HCM), places a severe
      burden on patients with advanced cancers. Bisphosphonates effectively correct HCM
      and reduce skeletal morbidity in patients with bone metastases. However, with the
      widespread use of bisphosphonates, the safety and convenience of therapy are
      emerging concerns. The delivery of effective doses of early bisphosphonates
      required a lengthy 24-hour i.v. infusion protocol because of renal tolerability
      issues. The introduction of more potent bisphosphonates with superior
      tolerability profiles has allowed therapy to be safely delivered via shorter i.v.
      infusions. Intravenous therapy with etidronate, clodronate, pamidronate,
      ibandronate, and zoledronic acid has been used to treat HCM and skeletal
      complications in cancer patients. Of these therapies, zoledronic acid (which can
      be safely administered via a 15-minute i.v. infusion) is the most convenient and
      effective and has demonstrated an excellent safety profile with long-term use.
      Zoledronic acid has also received the broadest regulatory approval of any
      bisphosphonate and can be used to treat HCM or bone lesions secondary to multiple
      myeloma and a wide variety of solid tumors, including breast, prostate, and lung
      cancers. In addition to the patient preference for shorter infusion times, the 15
      minute i.v. infusion protocol of zoledronic acid can provide benefits for
      infusion centers by potentially increasing patient throughput.

PMID- 15169989
TI  - Primary pulmonary synovial sarcoma: a case report and review of current
      diagnostic and therapeutic standards.
AB  - A 30-year-old female presented with hemoptysis, chest pain, and a rapidly
      enlarging pleural-based mass, and was found to have primary synovial sarcoma of
      the lung. Primary pulmonary sarcomas comprise <1% of all primary lung
      malignancies. They present clinically in young adults with cough, chest pain,
      shortness of breath, or hemoptysis, with a mass on x-ray and computerized
      tomography scan. Diagnosis is made by histology and immunohistochemistry.
      Histologic diagnosis has recently been supplemented by cytogenetic analysis,
      which offers important prognostic information. The mainstay of treatment remains
      complete surgical excision. Prognosis is poor, with an overall 5-year survival
      rate of 50%.

PMID- 15169990
TI  - Too old to care?
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at
      MGH (http://www.theschwarzcenter.org/rounds.asp). The Schwartz Center is a
      nonprofit organization dedicated to supporting and advancing compassionate health
      care delivery, which provides hope to the patient and support to caregivers, and
      encourages the healing process. The center sponsors the Schwartz Center Rounds, a
      monthly multidisciplinary forum where caregivers reflect on important
      psychosocial issues faced by patients, their families, and their caregivers, and
      gain insight and support from fellow staff members. Ageism is a pervasive problem
      throughout society. It is rooted in language, attitudes, beliefs, behaviors, and
      policies. Aging profoundly influences physiology, challenging the medical
      community to accommodate but not discriminate. The elderly are at an increased
      risk of disease and disability. Sixty percent of cancer occurs in people aged 65
      and older, and the population is aging. The treatment of cancer in the elderly is
      complicated by comorbidities and other physiological factors, particularly renal,
      bone marrow, and metabolic reserve. Caregivers have to treat patients in a manner
      that optimizes treatment and avoids anticipated harm. However, the caregiver is
      often faced with situations where they must balance their personal beliefs,
      professional values, and knowledge of medicine with their patients' preferences
      and needs. Discussion in the Rounds focused on age bias, drug toxicity, life
      prolongation, and symptom relief, with the role of the caregiver, and the
      relationship to the patient, being pivotal.

PMID- 15169991
TI  - The molecular perspective: nicotine and nitrosamines.

PMID- 15169995
TI  - Recent trends in HIV and other STIs in the United Kingdom: data to the end of
      2002.
AB  - Sexual health in the United Kingdom has deteriorated in recent years with further
      increases in HIV and other sexually transmitted infections (STIs) reported in
      2002. This paper describes results from the available surveillance data in the
      United Kingdom from the Health Protection Agency and its national collaborators.
      The data sources range from voluntary reports of HIV/AIDS from clinicians, CD4
      cell count monitoring, a national census of individuals living with HIV, and the
      Unlinked Anonymous Programme, to statutory reports of STIs from genitourinary
      medicine (GUM) clinics and enhanced STI surveillance systems. In 2002, an
      estimated 49500 adults aged over 15 years were living with HIV in the United
      Kingdom, of whom 31% were unaware of their infection. Diagnoses of new HIV
      infections have doubled from 1997 to 2002, mainly driven by heterosexuals who
      acquired their infection abroad. HIV transmission also continues within the
      United Kingdom, particularly among homo/bisexual men who, in 2002, accounted for
      80% of all newly diagnosed HIV infections acquired in the United Kingdom. New
      diagnoses of syphilis have increased eightfold, and diagnoses of chlamydia and
      gonorrhoea have doubled from 1997 to 2002 overall; STI rates disproportionately
      affect homo/bisexual men and young people. Effective surveillance is essential in
      the provision of timely information on the changing epidemiology of HIV and other
      STIs; this information is necessary for the targeting of prevention efforts and
      through providing baseline information against which progress towards targets can
      be monitored.

PMID- 15169999
TI  - Penile myiasis: a case report.
AB  - We report a case of penile myiasis in a Brazilian man caused by the larva of
      Dermatobia hominis. Myiasis is a parasitic disease of humans and other
      vertebrates caused by larvae of several fly species. Although urinary myiasis is
      well recognised, infestation of the genital tissue is a rare occurrence. Once the
      diagnosis has been made, the treatment is usually straightforward and
      uncomplicated.

PMID- 15169997
TI  - Approaches to the control of sexually transmitted infections in developing
      countries: old problems and modern challenges.
AB  - Sexually transmitted infections (STIs) constitute a huge health and economic
      burden for developing countries: 75-85% of the estimated 340 million annual new
      cases of curable STIs occur in these countries, and STIs account for 17% economic
      losses because of ill health. The importance of STIs has been more widely
      recognised since the advent of the HIV/AIDS epidemic, and there is good evidence
      that the control of STIs can reduce HIV transmission. The main interventions
      which could reduce the incidence and prevalence of STIs include primary
      prevention (information, education and communication campaigns, condom promotion,
      use of safe microbicides, and vaccines), screening and case finding among
      vulnerable groups (for example, pregnant women), STI case management using the
      syndromic approach, targeted interventions for populations at high risk (for
      example, sex workers), and in some circumstances (targeted) periodic mass
      treatment. The challenge is not just to develop new interventions, but to
      identify barriers to the implementation of existing tools, and to devise
      strategies for ensuring that effective STI control programmes are implemented in
      the future.

PMID- 15170000
TI  - The seroepidemiology of herpes simplex virus type 1 and 2 in Europe.
AB  - OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types
      1 and 2 in the general populations of eight European countries to better
      understand recent reported changes in disease epidemiology. METHODS: Belgium,
      Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and
      Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV
      2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External
      quality control was ensured through reference panel testing. RESULTS: Large
      intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were
      observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to
      57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in
      Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in
      Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands,
      6% in Czech Republic, and 4% in England and Wales. In all countries, probability
      of seropositivity for both infections increased with age. A large proportion of
      teenagers and young adults remain HSV-1 susceptible particularly in northern
      Europe. Women were significantly more likely to be HSV-2 seropositive in six of
      seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05)
      countries, particularly in northern Europe. No significant evidence of a
      protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex
      (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1
      and HSV-2 across Europe. The observation that a significant proportion of
      adolescents are now HSV-1 susceptible may have implications for transmission and
      clinical presentation of HSV-1 and HSV-2.

PMID- 15170002
TI  - Polymorph count for predicting non-gonococcal urethral infection: a model using
      Chlamydia trachomatis diagnosed by ligase chain reaction.
AB  - BACKGROUND/OBJECTIVES: The criteria for the diagnosis of non-gonococcal
      urethritis (NGU) on a Gram stained urethral smear are derived from previous
      studies which used culture as a diagnostic test for Chlamydia trachomatis. Our
      objectives were (1). to re-assess the relation between urethral polymorph count
      and C trachomatis infection, using ligase chain reaction (LCR) as the diagnostic
      test; and (2). to assess other possible predictors of C trachomatis infection
      such as symptoms, signs, demographic and behavioural variables. METHODS: We
      collected data from 363 men consecutively attending a genitourinary medicine
      clinic (excluding those with gonorrhoea and follow up visits) who had a urethral
      smear and a urethral LCR test for C trachomatis. The sensitivity and specificity
      of a discrete cut off in urethral polymorphonuclear leucocyte (PMNL) count as a
      diagnostic test for chlamydia urethritis were calculated. The associations
      between other variables, such as age and symptoms, and this infection were also
      estimated. RESULTS: 8% of men had C trachomatis infection and 26% of men had a
      PMNL count of 5 or more. Of those men with chlamydia 37% did not have NGU; 20% of
      men with NGU had chlamydia. Adjusted odds ratios for risk of chlamydial infection
      were significant for age less than 30 relative to 40 years and over (adj OR 13.6;
      95% confidence interval 1.69 to 110), a PMNL count of 20 or more (6.56; 2.15 to
      20.0), a PMNL count of 5-19 (3.59; 1.41 to 9.15), and the symptom of dysuria
      (3.27; 1.32 to 8.08). However a PMNL count of 5 or more was only 63% sensitive
      and 77% specific for C trachomatis infection. No association between sexual
      behaviour and chlamydial infection was found in this setting. CONCLUSIONS: The
      PMNL count is associated with presence of chlamydial infection but a large
      proportion of men with chlamydia have PMNL counts below the recommended cut off
      for a diagnosis of NSU. Lower age and the presence of symptoms may be as
      predictive as the urethral polymorph count for chlamydial urethritis and possibly
      for other urethral infections.

PMID- 15170001
TI  - Patient satisfaction with care for genital herpes: insights from a global survey.
AB  - OBJECTIVE: To describe patient experiences and views regarding genital herpes
      management. METHODS: Between February 2002 and January 2003, subjects with
      genital herpes were recruited via the International Herpes Alliance website and
      through banners on additional sites. Surveys were available in English, French,
      Spanish, Italian, and German and assessed views on access to care, diagnosis,
      related emotional experiences, educational resources, counselling,
      pharmacotherapy, and satisfaction with care. RESULTS: 2075 patient responses from
      78 countries were analysed. 49% reported their diagnosis was by culture (or other
      direct detection) and 9% by antibody test, while 34% reported they had been
      diagnosed by examination alone. 65% used a prescription antiviral therapy, 18% a
      topical antiviral therapy, and 17% an alternative therapy. Of 901 subjects who
      reported on frequency of antiviral use, only 30% reported a frequency consistent
      with a suppressive regimen while 59% of respondents said they would be likely to
      take daily therapy if it reduced the frequency of outbreaks. Patient satisfaction
      with management of physical symptoms was independently associated with duration
      of initial visit >or=15 minutes (adjusted odds ratio (OR) = 4.52), receiving a
      prescription (adj OR = 2.34) and receipt of a brochure/fact sheet (adj OR =
      2.14). Satisfaction with attention to emotional issues also correlated with the
      first two of these factors. CONCLUSIONS: Genital herpes management may be
      improved by including the use of confirmatory laboratory testing, employing a
      full range of antiviral therapy options, providing educational materials, and
      committing more time to counselling at the initial visit.

PMID- 15169996
TI  - Contraception choice for HIV positive women.
AB  - UNAIDS/WHO estimates that 42 million people are living with HIV/AIDS worldwide
      and 50% of all adults with HIV infection are women predominantly infected via
      heterosexual transmission. Women with HIV infection, like other women, may wish
      to plan pregnancy, limit their family, or avoid pregnancy. Health professionals
      should enable these reproductive choices by counselling and appropriate
      contraception provision at the time of HIV diagnosis and during follow up. The
      aim of this article is to present a global overview of contraception choice for
      women living with HIV infection including effects on sexual transmission risk.

PMID- 15170003
TI  - Comparison of latex agglutination, wet preparation, and culture for the detection
      of Trichomonas vaginalis.
AB  - OBJECTIVES: To compare the performance of three diagnostic methods for
      Trichomonas vaginalis infection-latex agglutination, saline wet mount, and
      culture. METHODS: Vaginal swabs from 3807 women attending antenatal clinics were
      tested for the presence of T vaginalis by latex agglutination. All positives and
      the following two negatives were tested by wet preparation and culture. RESULTS:
      The prevalence of infection by latex agglutination was 5.4%. Using an expanded
      gold standard based on the wet mount and culture results, the sensitivity of the
      latex agglutination test was 98.8% (95% CI 95.9 to 99.9) and specificity was 92.1
      (89.2 to 94.5). The kappa index for test agreement was 0.93 for latex and culture
      and 0.88 for latex and wet preparation. CONCLUSION: The latex agglutination test
      is a highly sensitive test for detecting T vaginalis infection. It is a simple
      rapid test and has the potential for use in screening and diagnostic settings.

PMID- 15170004
TI  - How is the high vaginal swab used to investigate vaginal discharge in primary
      care and how do GPs' expectations of the test match the tests performed by their
      microbiology services?
AB  - OBJECTIVES: To describe the management of vaginal discharge in general practice,
      with particular regard to the use of the high vaginal swab (HVS), and to compare
      GPs' expectations of this test with the processing and reporting undertaken by
      different laboratories. METHODS: A postal questionnaire survey of 2146 GPs in the
      North Thames area and postal questionnaire study of the 22 laboratories serving
      the same GPs were carried out. GPs were asked how they would manage a young woman
      with vaginal discharge and what information they would like on an HVS report.
      Laboratories were asked how they would process and report on the HVS sample from
      the same patient. RESULTS: Response rate was 26%. 72% of GPs would take an HVS
      and 62% would refer on to a genitourinary medicine (GUM) clinic. 45% would offer
      empirical therapy and 47% of these would treat for candida initially. 75% of GPs
      routinely request "M,C&S" on HVS samples but 55% only want to be informed about
      specific pathogens. Routine processing of HVS samples varies widely between
      laboratories and 86% only report specific pathogens. 78% of GPs would like to be
      offered a suggested diagnosis on HVS reports, and 74% would like a suggested
      treatment. 43% of laboratories ever provide a diagnosis, and 14% provide a
      suggested treatment. CONCLUSIONS: GPs frequently manage vaginal discharge and
      most of them utilise the HVS. GPs' expectations of the test are not well matched
      to laboratory processing or reporting of the samples.

PMID- 15170005
TI  - Diagnosis of genital chlamydia in primary care: an explanation of reasons for
      variation in chlamydia testing.
AB  - OBJECTIVES: To explore the reasons for the 40-fold variation in diagnostic
      testing for genital Chlamydia trachomatis by general practices. METHODS: A
      qualitative study with focus groups. We randomly selected urban and rural high
      and low testing practices served by Bristol, Hereford, and Gloucester
      microbiology laboratories. Open questions were asked about the investigation of C
      trachomatis in men and women in different clinical contexts. RESULTS: The high
      and low testing practices did not differ in their age/sex make-up or by
      deprivation indices. There were major differences between high and low chlamydia
      testing practices. Low testing practices knew very little about the epidemiology
      and presentation of genital chlamydia infection and did not consider it in their
      differential diagnosis of genitourinary symptoms until patients had consulted
      several times. Low testers were less aware that chlamydia was usually
      asymptomatic, thought it was an inner city problem, and had poor knowledge of how
      to take diagnostic specimens. High testing practices either had a general
      practitioner with an interest in sexual health or a practice nurse who had
      completed specialist training in family planning. High testing practices were
      more cognizant of the symptoms and signs of chlamydia and always considered it in
      their differential diagnosis of genitourinary symptoms, including patients
      attending family planning clinics. CONCLUSIONS: Any programme to increase
      chlamydia testing in primary care must be accompanied by an education and
      awareness programme especially targeted at low testing practices. This will need
      to include information about the benefits of testing and who, when, and how to
      test.

PMID- 15170006
TI  - The management of sexually transmitted infections by Australian general
      practitioners.
AB  - OBJECTIVES: To ascertain how frequently general practitioners (GPs) in Australia
      encounter sexually transmitted infections (STIs), how STIs are managed in general
      practice, and the characteristics of GPs who manage STIs. METHODS: Data were
      derived from the Bettering the Evaluation and Care of Health (BEACH) database.
      BEACH is a cross sectional survey of national GP activity. Approximately 1000 GPs
      per year each record details of 100 consecutive patient encounters. Details from
      April 1998 to March 2001 about frequency and pattern of STIs managed and the
      characteristics of GP managing them were analysed using SAS. RESULTS: 3030 GPs
      provided data on 303000 encounters. Only 521 problems managed were STIs. Viral
      STIs were most frequently managed including genital herpes (0.08 per 100
      encounters), genital warts (0.07 per 100 encounters). Gonorrhoea, syphilis,
      chlamydia, and trichomoniasis were rarely managed. Medication was prescribed at a
      rate of 56.1 per 100 STI contacts (95% CI 50.4 to 61.7). Antivirals were the most
      common followed by topical chemotherapeutics. GPs managing STIs were
      significantly younger and more likely to be female, urban, have fewer years in
      practice, work fewer sessions a week, work in a larger practice, have graduated
      in Australia, and hold the FRACGP (all p<0.005) than those who did not.
      CONCLUSION: Management of diagnosed STIs forms only a small part of a GP's
      workload in Australia. Genital herpes and warts are the most commonly managed
      conditions. GPs managing STIs are different from those who do not. Strategies to
      improve diagnosis, management, and screening should be evaluated.

PMID- 15170007
TI  - Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the
      cervix: a randomised placebo controlled trial.
AB  - BACKGROUND: Conventional therapies for human papillomavirus (HPV) infection are
      often associated with unsatisfactory response rates and high recurrence rates.
      The use of a systemic agent may more effectively control the virus. OBJECTIVES:
      To investigate the efficacy and safety of low dose oral isotretinoin in
      recalcitrant condylomata acuminata (RCA) of the cervix. METHODS: Double blind
      placebo controlled clinical trial. 60 women, aged 21-43 years, with RCA of the
      cervix, refractory to at least one conventional therapy, were randomly assigned
      to receive either isotretinoin, 0.5 mg/kg daily for 12 weeks (group 1), or
      placebo (group 2). RESULTS: Of the 28 evaluable group 1 patients, nine (32.1%)
      responded to the treatment completely, 11 (39.2%) responded partially, and eight
      (28.5%) did not respond. Of the 25 group 2 patients, no one responded to the
      treatment completely, two (8%) responded partially, and 23 (92%) did not respond.
      The therapeutic difference between patients receiving active and placebo therapy
      was statistically significant (chi(2) = 19.35, p<0.001). Only one (11.1%) of the
      complete responders experienced recurrence during the 12 month follow up. Side
      effects were generally mild and resolved upon completion of therapy. CONCLUSIONS:
      Compared to placebo, low dose oral isotretinoin showed considerable efficacy with
      insignificant and reversible side effects and a low recurrence rate. Isotretinoin
      may represent an efficacious and safe alternative systemic form of therapy for
      RCA of the cervix.

PMID- 15170009
TI  - Zafirlukast for severe recurrent vulvovaginal candidiasis: an open label pilot
      study.
AB  - BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) has been linked to allergic
      disease, particularly allergic rhinitis. OBJECTIVE: A pilot study to assess the
      possible use of the leukotriene receptor antagonist zafirlukast as a treatment
      for recurrent VVC. METHODS: 20 women with six or more symptomatic attacks of VVC
      in the past year (at least four proved microbiologically). Clinical atopy
      determined by the International Study for Asthma and Allergies in Childhood
      (ISAAC) questionnaire assessed blindly. Monitoring by daily symptom diary and
      self taken vaginal swabs. Treatment with zafirlukast 20 mg twice daily for 24
      weeks or until three microbiologically confirmed episodes of VVC. Response
      assessed by daily symptom diary and self taken vaginal swabs. Subjective response
      scales for improvement, side effects, and change in other allergic disease
      completed when stopping treatment. Semistructured telephone interview 1 year
      after stopping medication. RESULTS: 14 patients (70%) reported a subjective
      response on the improvement response scale. Six (30%) showed a complete response
      with no further symptomatic attacks of VVC or negative swabs when symptomatic.
      Seven (37%) remained symptom free 18 months after entering the study-that is, 12
      months after stopping therapy. 11 (58%) remained symptom free for at least 3
      months after stopping therapy. This does not include one patient who remained
      symptom free but continued on zafirlukast because of an improvement in her
      asthma. There was no clear relation between response and atopic status. Six of
      nine atopic subjective responders reported improvements in other allergic
      symptoms. Side effects were minimal; one seemed clearly attributable to the drug.
      CONCLUSION: Zafirlukast offers a potential new treatment for recurrent VVC that
      requires confirmation in controlled studies.

PMID- 15170010
TI  - Developing national outcome standards for the management of gonorrhoea and
      genital chlamydia in genitourinary medicine clinics.
AB  - BACKGROUND: Measuring clinical performance within a framework of clinical
      governance is increasingly important for monitoring improvements in patient care.
      Standards for quality indicators must, however, be achievable and evidence based.
      We describe an approach to the development of national standards for measuring
      outcomes of care for gonorrhoea and genital chlamydia in genitourinary medicine
      clinics. METHODS: Two standards for each infection, one reflecting quality of
      case management and one reflecting partner management were chosen by consensus. A
      systematic review of published and unpublished UK studies about gonorrhoea and
      chlamydia management was carried out and weighted averages calculated for each
      parameter, stratified by location. Genitourinary medicine practitioners around
      the country were also asked for their opinion about desirable values for each
      standard and the results compared. Variability in performance between centres was
      examined using Shewhart's control charts. RESULTS: We identified 17 reports about
      gonorrhoea outcomes and 14 about chlamydia. There was marked heterogeneity in
      results according to geographical location and different standards were set for
      clinics in and out of London. Opinions from practitioners suggested much higher
      standards than the values obtained from the systematic review. There was evidence
      for special cause variation related to management of gonorrhoea and chlamydia in
      London clinics. CONCLUSIONS: Standards set using expert opinion are unrealistic
      when compared to evidence of what is achievable. Evidence based methods should
      therefore be used to derive outcome standards for case management gonorrhoea and
      chlamydia. The control chart method identified clinics where investigation to
      find reasons for special cause variation in performance should be undertaken to
      change practice.

PMID- 15170011
TI  - Low prevalence of cervical infections in women with vaginal discharge in west
      Africa: implications for syndromic management.
AB  - OBJECTIVES: To measure prevalence and risk factors for cervical infections among
      a large sample of women consulting for vaginal discharge in west Africa and to
      evaluate its syndromic management through a two visit algorithm. METHODS: In 11
      health centres in Benin, Burkina Faso, Ghana, Guinee, and Mali 726 women who
      presented with a vaginal discharge without abdominal pain and who denied being a
      sex worker (SW) were enrolled. Cervical samples were tested for the detection of
      Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with polymerase chain
      reaction (PCR) assays. All participants were treated with single dose (2 g)
      metronidazole and clotrimazole cream for 3 days. They were randomised to be told
      either to come back on day 7 only if there was no improvement in the discharge
      (group A), or to come back on day 7 regardless of response to treatment (group
      B). RESULTS: Overall, the prevalence of NG and CT was only 1.9% (14/726) and 3.2%
      (23/726) respectively. Risk factors previously recommended by the WHO were not
      associated with the presence of cervical infection, with the exception of the
      number of sex partners in the past 3 months. When taken together, these risk
      factors had a positive predictive value of only 6.4% to identify cervical
      infections. Prevalence of cervical infection was not higher in women who came
      back on day 7, regardless of the strategy used. Prevalence of NG/CT was lower in
      Ghana and Benin (5/280, 1.8%), where comprehensive interventions for SW have been
      ongoing for years, than in the three other countries (27/446, 6.1%, p = 0.01).
      CONCLUSIONS: NG and CT infections are uncommon in west African women who consult
      for vaginal discharge and who are not SW. Syndromic management of vaginal
      discharge should focus on the proper management of vaginitis. The control of
      gonococcal and chlamydial infection should be redesigned around interventions
      focusing on sex workers.

PMID- 15170012
TI  - Increasing risk behaviour and high levels of undiagnosed HIV infection in a
      community sample of homosexual men.
AB  - OBJECTIVES: To estimate changes in sexual behaviour over time. To examine the
      proportion of undiagnosed HIV infection in a community sample of homosexual men.
      To explore the relation between HIV status, diagnosis, and sexual behaviour.
      METHODS: Five cross sectional surveys of men attending selected gay community
      venues in London between 1996 and 2000 (n = 8052). Men were recruited in 45 to 58
      social venues (including bars, clubs, and saunas) across London. Participants
      self completed an anonymous behavioural questionnaire. In 2000, participants in
      community venues provided anonymous saliva samples for testing for anti-HIV
      antibody. RESULTS: The proportion of men having unprotected anal intercourse
      (UAI) increased significantly each year from 30% in 1996 to 42% in 2000
      (p<<0.001). In 2000, 132 of 1206 (10.9%) saliva samples were HIV antibody
      positive. Of the HIV saliva antibody positive samples, 43/132 (32.5%) were
      undiagnosed. Around half of both diagnosed and undiagnosed HIV saliva positive
      men reported UAI in the past year. Of the 83% of men who reported their current
      perceived HIV status, 4.1% reported an incorrect status. HIV antibody positivity
      was associated with increasing numbers of UAI partners, and having a sexually
      transmitted infection (STI) in the past year (OR 2.15). CONCLUSIONS: Homosexual
      men continue to report increasing levels of UAI. HIV prevalence is high in this
      group, with many infections remaining undiagnosed. The high level of risky
      behaviour in HIV positive men, regardless of whether they are diagnosed, is of
      public health concern, in an era when HIV prevalence, antiretroviral resistance,
      and STI incidence are increasing.

PMID- 15170014
TI  - Sexually transmitted infections in women who have sex with women.
AB  - OBJECTIVES: To describe the prevalence of sexually transmitted infection (STIs)
      in a sample of women who have sex with women (WSW) and to identify risk factors
      for the acquisition of STI. METHOD: Cross sectional survey. Questionnaire for
      demographic, sexual history, and sexual practice data linked with the results of
      genitourinary examination. 708 new patients attending two sexual health clinics
      for lesbians and bisexual women in London were surveyed. RESULTS: A majority of
      WSW reported sexual histories with men (82%). Bacterial vaginosis and candida
      species were commonly diagnosed (31.4% and 18.4% respectively). Genital warts,
      genital herpes, and trichomoniasis were infrequently diagnosed (1.6%, 1.1%, and
      1.3% respectively). Chlamydia, pelvic inflammatory disease, and gonorrhoea
      infections were rare (0.6%, 0.3%, and 0.3% respectively) and diagnosed only in
      women who had histories of sex with men. CONCLUSIONS: Although we have
      demonstrated a low prevalence of STI, WSW may have sexual histories with men as
      well as women or histories of injecting drug use, and are therefore vulnerable to
      sexually transmitted or blood borne infections. Diagnosis of trichomoniasis,
      genital herpes, and genital warts in three women who had no history of sex with
      men implies that sexual transmission between women is possible.

PMID- 15170013
TI  - Acceptability of COL-1492, a vaginal gel, among sex workers in one Asian and
      three African cities.
AB  - OBJECTIVES: To evaluate the acceptability of COL-1492, a vaginal gel containing
      52.5 mg nonoxynol-9, in an HIV prevention trial. METHODS: Sex workers
      participating in a phase II/III triple blind, randomised trial in Benin, Cote
      d'Ivoire, South Africa, and Thailand were interviewed on the gel's acceptability
      at monthly scheduled clinic visits. Safer sex counselling, male condoms, and
      study gels were given at each monthly visit; a gynaecological examination and HIV
      test were performed. Phase III interviews considered the participants'
      appreciation of the gel. On the first, second, and fifth follow up visits, the
      study volunteers completed more extensive questionnaires. RESULTS: Responses were
      similar between treatment arms. Women indicated not liking their gel in 1.8% of
      the visits; 98.1% of the women found the gel easy to apply; 30.1% said that it
      affected sexual intercourse. These effects were mostly improvements (92.6%) by
      facilitating intercourse (73.6%). Intercourse was more often affected in women
      reporting painful sexual intercourse (OR: 2.59 (95% CI 1.63 to 4.12)) and in
      older women. The latter effect differed among centres. CONCLUSION: Most
      participants found their assigned gel acceptable and the vast majority of
      reported effects on intercourse were favourable. The type of gel had no
      significant impact on the findings.

PMID- 15170015
TI  - Barriers to HIV testing: a survey of GUM clinic attendees.

PMID- 15170016
TI  - Diagnosis and exclusion of gonorrhoea in women.

PMID- 15170017
TI  - HPV in cervix and vagina.

PMID- 15170018
TI  - Factors that may increase HIV testing uptake in those who decline to test.

PMID- 15170019
TI  - Chaperoning in GUM clinics.

PMID- 15170020
TI  - Monitoring mast cell activation by prostaglandin D2 in vivo.

PMID- 15170021
TI  - Breathlessness during exercise in COPD: how do the drugs work?

PMID- 15170022
TI  - Measuring quality of life in patients with sleep apnoea: whose life is it anyway?

PMID- 15170023
TI  - Plasma 9alpha,11beta-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell
      activation by allergen in bronchial asthma.
AB  - BACKGROUND: Prostaglandin D(2) (PGD(2)) is a major cyclooxygenase product
      generated by activated mast cells during an allergic response. Assessment of
      PGD(2) and its metabolites in patients with asthma has mostly been performed in
      urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma
      determinations have been performed only sporadically. METHODS: In 32 patients
      with allergic asthma and 50 healthy non-allergic controls, baseline plasma and
      urinary levels of 9alpha,11beta-PGF(2), a primary PGD(2) metabolite, were
      assessed by gas chromatography/mass spectrometry. Serum tryptase levels were
      measured by fluoroenzyme immunoassay and urinary leukotriene E(4) (LTE(4)) by
      ELISA. In a subgroup of 10 asthmatics (randomly selected from the 32 study
      patients) in whom bronchial allergen challenges with specific allergens
      (Dermatophagoides pteronyssinus, n = 4, mixed grass pollens, n = 6) were carried
      out, measurements were taken both before and after provocation. RESULTS: At
      baseline no significant differences between mean plasma and urinary levels of the
      PGD(2) metabolite and serum tryptase levels were found in asthmatics or controls.
      Asthmatic patients had significantly higher urinary LTE(4) levels. Allergen
      challenge resulted in a significant early increase in the mean plasma
      9alpha,11beta-PGF(2) level and only a borderline but significant increase in the
      urinary 9alpha,11beta-PGF(2) level within 2 hours after provocation. The
      challenge did not produce statistically significant changes in serum tryptase
      levels. Urinary LTE(4) levels remained significantly increased 4 hours after
      provocation. CONCLUSIONS: PGD(2) is actively involved in the early asthmatic
      response to allergens. Measurement of 9alpha,11beta-PGF(2) release into plasma
      rather than urine following allergen challenge is a sensitive marker of enhanced
      PGD(2) synthesis, most probably due to mast cell activation.

PMID- 15170025
TI  - Gas chromatography/mass spectrometry analysis of exhaled leukotrienes in
      asthmatic patients.
AB  - BACKGROUND: Leukotriene-like immunoreactivity has been detected in exhaled breath
      condensate (EBC), but definitive evidence for the presence of leukotrienes (LTs)
      in this biological fluid is not available. A study was undertaken to determine
      whether LTC(4), LTD(4), LTE(4), and LTB(4) are measurable in EBC by gas
      chromatography/mass spectrometry and to quantify exhaled LTs in adults and
      children with asthma and in control subjects. METHODS: Twenty eight adults and 33
      children with mild to moderate persistent asthma treated with inhaled
      corticosteroids and age matched healthy controls (50 adults and 50 children) were
      studied. LTB(4), LTC(4), LTD(4), and LTE(4) in EBC were measured by gas
      chromatography/mass spectrometry. RESULTS: LTD(4), LTE(4), and LTB(4) were
      detectable in all samples. Concentrations of LTC(4) in EBC were either close to
      or below the detection limit of 1 pg/ml. Median exhaled LTD(4), LTE(4), and
      LTB(4) concentrations in asthmatic adults were increased 4.1-fold (p<0.001), 1.8
      fold (p<0.01), and 2.6-fold (p<0.001), respectively, compared with values in
      healthy adults. Median exhaled LTD(4), LTE(4), and LTB(4) concentrations in
      asthmatic children were increased 2.8-fold (p<0.001), 1.3-fold (p<0.001), and 1.6
      fold (p<0.001), respectively, compared with those in healthy children. In
      patients with asthma there was a correlation between exhaled LTD(4) and LTE(4) in
      both adults (r = 0.87, p<0.0001) and children (r = 0.78, p<0.0001). CONCLUSIONS:
      Gas chromatography/mass spectrometry can be used to accurately quantify exhaled
      LTs which are increased in asthmatic adults and children compared with controls.

PMID- 15170026
TI  - Effect of salmeterol on respiratory muscle activity during exercise in poorly
      reversible COPD.
AB  - BACKGROUND: Some patients with irreversible chronic obstructive pulmonary disease
      (COPD) experience subjective benefit from long acting bronchodilators without
      change in forced expiratory volume in 1 second (FEV(1)). Dynamic hyperinflation
      is an important determinant of exercise induced dyspnoea in COPD. We hypothesised
      that long acting bronchodilators improve symptoms by reducing dynamic
      hyperinflation and work of breathing, as measured by respiratory muscle pressure
      time products. METHODS: Sixteen patients with "irreversible" COPD (<10%
      improvement in FEV(1) following a bronchodilator challenge; mean FEV(1) 31.1%
      predicted) were recruited into a randomised, double blind, placebo controlled,
      crossover study of salmeterol (50 micro g twice a day). Treatment periods were of
      2 weeks duration with a 2 week washout period. Primary outcome measures were end
      exercise isotime transdiaphragmatic pressure-time product and dynamic
      hyperinflation as measured by inspiratory capacity. RESULTS: Salmeterol
      significantly reduced the transdiaphragmatic pressure-time product (294.5 v 348.6
      cm H(2)O/s/min; p = 0.03), dynamic hyperinflation (0.22 v 0.33 litres; p =
      0.002), and Borg scores during endurance treadmill walk (3.78 v 4.62; p = 0.02).
      There was no significant change in exercise endurance time. Improvements in
      isotime Borg score were significantly correlated to changes in tidal
      volume/oesophageal pressure swings, end expiratory lung volume, and inspiratory
      capacity, but not pressure-time products. CONCLUSIONS: Despite apparent "non
      reversibility" in spirometric parameters, long acting bronchodilators can cause
      both symptomatic and physiological improvement during exercise in severe COPD.

PMID- 15170030
TI  - NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with
      COPD and low body weight.
AB  - BACKGROUND: Weight loss, mostly due to skeletal muscle atrophy, is a frequent and
      clinically relevant problem in patients with chronic obstructive pulmonary
      disease (COPD). The molecular mechanisms underlying this phenomenon are unclear.
      This study sought to investigate whether activation of the nuclear transcription
      factor NF-kappaB and upregulation of the inducible form of nitric oxide synthase
      (iNOS) occur in the skeletal muscle of patients with COPD and low body weight as
      potential molecular mechanisms leading to cachexia METHODS: NF-kappaB DNA binding
      activity was determined by electromobility shift assay and the immunoreactivity
      of its inhibitory subunit IkappaB-kappa and that of iNOS by Western blot analysis
      in biopsy specimens of the quadriceps femoris muscle of seven COPD patients with
      normal body mass index (BMI, 27.5 (1) kg/m(2)) and seven patients with low BMI
      (18.5 (1) kg/m(2)). RESULTS: Compared with patients with normal body weight,
      those with low BMI showed a 30% increase in NF-kappaB DNA binding activity, a
      lower expression of IkappaB-alpha (3.37 (0.47) IOD v 5.96 (0.75) IOD, p<0.05;
      mean difference 2.59; 95% CI -4.53 to -0.65) and higher iNOS expression (1.51
      (0.29) IOD v 0.78 (0.11) IOD, p<0.05; mean difference 0.74; 95% CI 0.04 to 1.42).
      CONCLUSIONS: NF-kappaB activation and iNOS induction occur in skeletal muscle of
      COPD patients with low body weight. These changes might contribute to the
      molecular pathogenesis of cachexia in COPD.

PMID- 15170028
TI  - Inspiratory muscle load and capacity in chronic heart failure.
AB  - BACKGROUND: Although breathlessness is common in chronic heart failure (CHF), the
      role of inspiratory muscle dysfunction remains unclear. We hypothesised that
      inspiratory muscle endurance, expressed as a function of endurance time (Tlim)
      adjusted for inspiratory muscle load and inspiratory muscle capacity, would be
      reduced in CHF. METHODS: Endurance was measured in 10 healthy controls and 10
      patients with CHF using threshold loading at 40% maximal oesophageal pressure
      (Poes(max)). Oesophageal pressure-time product (PTPoes per cycle) and Poes(max)
      were used as indices of inspiratory muscle load and capacity, respectively.
      RESULTS: Although Poes(max) was slightly less in the CHF group (-117.7 (23.6) v 
      100.0 (18.3) cm H(2)O; 95% CI -37.5 to 2.2 cm H(2)O, p = 0.1), Tlim was greatly
      reduced (1800 v 306 (190) s; 95% CI 1368 to 1620 s, p<0.0001) and the observed
      PTPoes per cycle/Poes(max) was increased (0.13 (0.05) v 0.21 (0.04); 95% CI -0.11
      to -0.03, p = 0.001). Most of this increased inspiratory muscle load was due to a
      maladaptive breathing pattern, with a reduction in expiratory time (3.0 (5.8) v
      1.1 (0.3) s; 95% CI 0.3 to 3.5 s, p = 0.03) accompanied by an increased
      inspiratory time relative to total respiratory cycle (Ti/Ttot) (0.43 (0.14) v
      0.62 (0.07); 95% CI -0.3 to -0.1, p = 0.001). However, log Tlim, which
      incorporates the higher inspiratory muscle load to capacity ratio caused by this
      altered breathing pattern, was >/=85% predicted in seven of 10 patients.
      CONCLUSIONS: Although a marked reduction in endurance time was observed in CHF,
      much of this reduction was explained by the increased inspiratory muscle load to
      capacity ratio, suggesting that the major contributor to task failure was a
      maladaptive breathing pattern rather than impaired inspiratory muscle endurance.

PMID- 15170031
TI  - Can endobronchial biopsy analysis be recommended to discriminate between asthma
      and COPD in routine practice?
AB  - BACKGROUND: International guidelines stress the importance of accurately
      discriminating between asthma and chronic obstructive pulmonary disease (COPD).
      Although characteristic pathological features have been described for both
      conditions, their discriminatory power has never been systematically assessed.
      METHODS: Endobronchial biopsy (EBB) specimens from patients with a clear clinical
      diagnosis of asthma and COPD (50 per group) were examined by three pathologists
      in a double blind manner. They were asked to propose a pathological diagnosis of
      either asthma or COPD and to analyse qualitatively the most frequent
      abnormalities reported in the literature. RESULTS: The sensitivity and
      specificity of EBB ranged from 36% to 48% and from 56% to 79%, respectively.
      Eosinophils strongly biased the pathological diagnoses in favour of asthma,
      whereas their estimated prevalence was similar (11-37% in asthma and 13-41% in
      COPD). Metaplasia (11-39% in COPD, 1-18% in asthma) and epithelial inflammation
      (28-61% in COPD, 11-38% in asthma) tended to be specific to COPD, whereas
      epithelial desquamation (80-98% in asthma, 61-88% in COPD) and basement membrane
      thickening (71-94% in asthma, 53-88% in COPD) tended to be associated with
      asthma. There was acceptable intra- and inter-observer agreement only for
      metaplasia and epithelial eosinophils. CONCLUSIONS: Specific histopathological
      features of asthma and COPD probably exist, but current routine analysis
      procedures to assess EBB specimens are not sufficiently discriminatory. This
      might be rectified by improving pathological definitions.

PMID- 15170033
TI  - Inter-observer variation between pathologists in diffuse parenchymal lung
      disease.
AB  - BACKGROUND: There have been few inter-observer studies of diffuse parenchymal
      lung disease (DPLD), but the recent ATS/ERS consensus classification provides a
      basis for such a study. METHODS: A method for categorising numerically the
      percentage likelihood of these differential diagnoses was developed, and the
      diagnostic confidence of pathologists using this classification and the
      reproducibility of their diagnoses were assessed. RESULTS: The overall kappa
      coefficient of agreement for the first choice diagnosis was 0.38 (n = 133
      biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies.
      Weighted kappa coefficients of agreement, quantifying the level of probability of
      individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75).
      However, in 18% of biopsy specimens the diagnosis was given with low confidence.
      Over 50% of inter-observer variation related to the diagnosis of non-specific
      interstitial pneumonia and, in particular, its distinction from usual
      interstitial pneumonia. CONCLUSION: These results show that the ATS/ERS
      classification can be applied reproducibly by pathologists who evaluate DPLD
      routinely, and support the practice of taking multiple biopsy specimens.

PMID- 15170032
TI  - A new standardised and self-administered quality of life questionnaire specific
      to obstructive sleep apnoea.
AB  - BACKGROUND: A short, standardised, self-administered quality of life
      questionnaire would be a useful addition to the outcome measures in obstructive
      sleep apnoea (OSA) research. A study was therefore undertaken to validate a new
      OSA specific self-administered questionnaire (the Quebec Sleep Questionnaire,
      QSQ) for use in clinical trials. METHODS: This study followed a description of
      health related quality of life in patients with OSA. Construct validity and
      responsiveness were tested by comparing the baseline and changes in domain scores
      (daytime sleepiness, diurnal symptoms, nocturnal symptoms, emotions, social
      interactions) with those of questionnaires measuring related constructs (SF-36,
      Epworth Sleepiness Scale, Beck Depression Inventory, SCL-90, and Functional
      Outcomes in Sleep Questionnaire). RESULTS: Sixty patients (48 men) of mean (SD)
      age 55 (10) years participated in the study. In the analysis of the
      discriminative function of the questionnaire, moderate to high correlations were
      found between the scores in each domain of the QSQ and the corresponding
      questionnaires. In the analysis of its evaluative function significant
      differences were found in score changes between patients who were treated and
      those who were not, and moderate to high correlations were seen between changes
      in scores in the QSQ and changes in the corresponding questionnaires. Most of
      these correlations met the a priori predictions made regarding their magnitude.
      CONCLUSION: The QSQ is a valid measure of health related quality of life in
      patients with OSA and is sensitive to treatment induced changes.

PMID- 15170037
TI  - Seasonality of long term wheezing following respiratory syncytial virus lower
      respiratory tract infection.
AB  - BACKGROUND: It is well known that respiratory syncytial virus (RSV) lower
      respiratory tract infection (LRTI) is associated with subsequent wheezing
      episodes, but the precise natural course of wheezing following RSV LRTI is not
      known. This study aimed to determine the continuous development of wheezing
      following RSV LRTI in children up to the age of 3 years. METHODS: A prospective
      cohort study was performed in 140 hospitalised infants with RSV LRTI. Continuous
      follow up data were obtained with a unique log in which parents noted daily
      respiratory symptoms. RESULTS: A marked decrease in wheezing was seen during the
      first year of follow up. The burden of wheezing following RSV LRTI was observed
      during the winter season. Signs of airflow limitation during RSV LRTI were
      strongly associated with wheezing during the follow up period. Total and specific
      serum immunoglobulin E levels, patient eczema, and parental history of atopy were
      not associated with wheezing. CONCLUSIONS: Airway morbidity following RSV LRTI
      has a seasonal pattern, which suggests that viral upper respiratory tract
      infections are the predominant trigger for wheezing following RSV LRTI. There is
      a significant decrease in airway symptoms during the first 12 months after
      admission to hospital. Simple clinical variables, but not allergic risk factors,
      can predict the development of wheezing following RSV LRTI.

PMID- 15170034
TI  - HRCT diagnosis of diffuse parenchymal lung disease: inter-observer variation.
AB  - BACKGROUND: This study was designed to measure inter-observer variation between
      thoracic radiologists in the diagnosis of diffuse parenchymal lung disease (DPLD)
      using high resolution computed tomography (HRCT) and to identify areas of
      difficulty where expertise, in the form of national panels, would be of
      particular value. METHODS: HRCT images of 131 patients with DPLD (from a tertiary
      referral hospital (n = 66) and regional teaching centres (n = 65)) were reviewed
      by 11 thoracic radiologists. Inter-observer variation for the first choice
      diagnosis was quantified using the unadjusted kappa coefficient of agreement.
      Observers stated differential diagnoses and assigned a percentage likelihood to
      each. A weighted kappa was calculated for the likelihood of each of the six most
      frequently diagnosed disease entities. RESULTS: Observer agreement on the first
      choice diagnosis was moderate for the entire cohort (kappa = 0.48) and was higher
      for cases from regional centres (kappa = 0.60) than for cases from the tertiary
      referral centre (kappa = 0.34). 62% of cases from regional teaching centres were
      diagnosed with high confidence and good observer agreement (kappa = 0.77). Non
      specific interstitial pneumonia (NSIP) was in the differential diagnosis in most
      disagreements (55%). Weighted kappa values quantifying the likelihood of specific
      diseases were moderate to good (mean 0.57, range 0.49-0.70). CONCLUSION: There is
      good agreement between thoracic radiologists for the HRCT diagnosis of DPLD
      encountered in regional teaching centres. However, cases diagnosed with low
      confidence, particularly where NSIP is considered as a differential diagnosis,
      may benefit from the expertise of a reference panel.

PMID- 15170038
TI  - Enhanced virulence, airway inflammation and impaired lung function induced by
      respiratory syncytial virus deficient in secreted G protein.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection can cause bronchial
      hyperresponsiveness and asthma exacerbations. In mice it results in airway
      inflammation and airway hyperresponsiveness. Since viral factors influencing
      these responses are not well defined, a study was undertaken to investigate the
      role of secreted G protein of human RSV in determining virulence, inflammatory
      responses, and changes in lung function. METHODS: BALB/c mice were infected with
      a spontaneous mutant of RSV deficient in secreted G protein (RSV-DeltasG) or with
      wild type RSV (RSV-WT). Viral titres, numbers of pulmonary inflammatory cells,
      and concentrations of interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10
      in bronchoalveolar lavage (BAL) fluid were determined. Airway function was
      assessed at baseline and following methacholine provocation using barometric
      whole body plethysmography. RESULT: Following infection with RSV-DeltasG, viral
      titres were increased 50-fold compared with RSV-WT. Influx of eosinophils and
      macrophages to the lung and concentrations of IFN-gamma and IL-10 in BAL fluid
      were also significantly higher following infection with RSV-DeltasG. Airway
      function, both at baseline and after methacholine provocation, was significantly
      decreased following infection with RSV-DeltasG compared with RSV-WT. CONCLUSION:
      Secreted G protein is likely to be a regulatory factor in RSV infection limiting
      infectivity of the virus, inflammatory responses in the lungs, and reduction in
      lung function.

PMID- 15170039
TI  - Clinical features, aetiology and outcome of empyema in children in the north east
      of England.
AB  - BACKGROUND: The incidence of empyema in children in the UK is increasing. The
      reason for this is unclear. A prospective study was undertaken to investigate the
      clinical features, aetiology, and outcome of cases of empyema and parapneumonic
      effusion presenting to a tertiary paediatric respiratory centre between February
      1997 and August 2001. METHOD: Routine bacterial culture of blood and pleural
      fluid was performed for 47 cases. Forty three pleural fluid specimens, culture
      negative for pneumococcus, were analysed for pneumococccal DNA by real time
      polymerase chain reaction (PCR). Penicillin susceptibility was determined for DNA
      positive specimens using complementary PCR assay. Capsular serotype specific
      antigen detection was by enzyme immunoassay (EIA) using monoclonal antibodies to
      serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Clinical data
      were obtained from patient notes, supplemented by a postal questionnaire.
      RESULTS: The median (range) age of the patients was 5.6 (0.6-16.9) years and 70%
      were male. The median (range) duration of illness before referral to hospital was
      5 (0-25) days. Forty five (96%) had received antibiotics before referral; 32
      (68%) required decortication and eight (21%) thoracocentesis. Median
      postoperative stay was 4 days (2-8). Thirty two (75%) pneumococcal culture
      negative specimens were pneumococcal DNA positive; 17 (53%) of these were
      serotype 1. All were penicillin sensitive. CONCLUSIONS: Pneumococcus is the major
      pathogen in childhood empyema and serotype 1 is the prevalent serotype. This has
      implications for vaccine development and immunisation strategy as the current 7
      valent pneumococcal conjugate vaccine does not protect against serotype 1.

PMID- 15170040
TI  - Prevalence and clonality of Burkholderia cepacia complex genomovars in UK
      patients with cystic fibrosis referred for lung transplantation.
AB  - BACKGROUND: It has previously been reported that patients infected with
      Burkholderia cenocepacia (genomovar III) before lung transplantation have a
      poorer outcome than those with other B. cepacia complex infections. METHODS: An
      extensive study was conducted to determine the prevalence and clonality of B.
      cepacia complex genomovars isolated from patients referred for transplant
      assessment between 1989 to the present and, where appropriate, whether strain
      type was related to transplant outcome. RESULTS: Isolates from 29 patients were
      identified as B. cepacia complex organisms by molecular analysis. Thirteen
      patients (45%) were infected with the highly transmissible ET-12 strain of B.
      cenocepacia recA lineage III-A, while all remaining patients were infected with
      genetically unique B. cenocepacia, B. multivorans, and B. vietnamiensis strains.
      All previously reported deaths following transplantation were associated with ET
      12 infection. CONCLUSIONS: The ET-12 strain is the predominant cause of B.
      cenocepacia infections in patients with cystic fibrosis referred to our pulmonary
      transplant centre and is associated with poor transplant outcomes using standard
      treatment regimens.

PMID- 15170042
TI  - Treatment with epoprostenol of pulmonary arterial hypertension following mitral
      valve replacement for mitral stenosis.
AB  - Pulmonary hypertension frequently complicates mitral stenosis. Increased
      pulmonary artery pressure results from raised left atrial pressure, pulmonary
      arteriolar constriction, and obliterative changes in the pulmonary vascular bed,
      and usually responds to surgical relief of mitral stenosis. However, severe
      pulmonary hypertension may persist after surgical treatment of mitral stenosis.
      We describe a patient whose severe pulmonary hypertension following mitral valve
      replacement was treated successfully with continuous intravenous epoprostenol.

PMID- 15170044
TI  - Variations in mortality in acute COPD may reflect nihilism as well as resources.

PMID- 15170045
TI  - Do inhaled corticosteroids slow FEV1 decline in COPD after all?

PMID- 15170041
TI  - Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology.
AB  - The molecular basis of alpha(1)-antitrypsin deficiency is reviewed and is shown
      to be due to the accumulation of mutant protein as ordered polymers within the
      endoplasmic reticulum of hepatocytes. The current goals are to determine the
      cellular response to polymeric alpha(1)-antitrypsin and to develop therapeutic
      strategies to block polymerisation in vivo.

PMID- 15170046
TI  - Ethics of placebo controlled studies of inhaled steroids for COPD.

PMID- 15170047
TI  - Prophylactic antibiotic treatment of bronchiectasis with azithromycin.

PMID- 15170049
TI  - Recurrence of acute respiratory failure following use of waterproofing sprays.

PMID- 15170051
TI  - Effect of PM10 on H. influenzae and S. pneumoniae.

PMID- 15170048
TI  - Delays in diagnosis of OSAHS.

PMID- 15170050
TI  - Early life antibiotics and asthma.

PMID- 15170055
TI  - Reconsidering Zoanthus spp. diversity: molecular evidence of conspecifity within
      four previously presumed species.
AB  - We have conducted the first phylogenetic study to our knowledge of Zoanthus in
      the northern hemisphere by sequencing and analysing the mitochondrial cytochrome
      oxidase subunit 1 (COI) gene. Various unidentified Zoanthus specimens and samples
      of what have been assumed to be four discrete species (Z. pacificus, Z.
      sansibaricus, Z. gnophodes, Z. erythrochloros) were collected from four field
      sites in Kagoshima Prefecture, Japan. Based on our obtained COI gene sequences,
      all but one of our collected Zoanthus samples appear to be conspecific, with
      nearly 100.00% base pair matching. Genetic results are further backed up by
      collected polyp diameter, tentacle count, and mesentary count data. These results
      indicate a need to reconsider and re-analyze current Zoanthus classification and
      identification. Possible reasons for the large morphological variation in the
      same genotype in Zoanthus are also discussed.

PMID- 15170056
TI  - Chemical modification of glycerinated stalks shows tyrosine residues essential
      for spasmoneme contraction of Vorticella sp.
AB  - Chemical modification of glycerinated stalks of Vorticella with TNM is used to
      investigate the role of tyrosine residues in the Ca(2+)-induced contraction of
      the spasmoneme. Tetranitromethane (TNM) is often employed as a specific reagent
      for the nitration of tyrosine residues in a protein at neutral and slightly
      alkaline pHs although TNM can also oxidize cysteine residues in the acidic and
      neutral pH range. Prior incubation with Ca(2+) of stalks to be treated with TNM
      can protect the spasmoneme from irreversible denaturation. On the other hand, TNM
      treatment in the absence of free Ca(2+) causes an irreversible denaturation of
      the spasmoneme. It was revealed by us that an isolated Ca(2+)-binding protein
      called spasmin could not bind with Ca(2+) after TNM treatment, even if the
      treatment was performed in the presence of Ca(2+). In an additional experiment,
      we confirmed that the chemical modification of cysteine residues in the
      spasmoneme with N-7-dimethyl-amino-4methyl- coumarinyl- maleimide (DACM) has no
      effect on the contractibility. These results suggest that tyrosine residues in
      spasmin are essential for spasmoneme contraction and are protected from TNM in
      the presence of Ca(2+) when spasmin binds with its receptor protein in the
      spasmoneme.

PMID- 15170054
TI  - Ecdysteroids during early embryonic development in silkworm Bombyx mori:
      metabolism and functions.
AB  - It has been well established that eggs of insects, including those of the
      silkworm Bombyx mori, contain various molecular species of ecdysteroids in free
      and conjugated forms. In B. mori eggs, 20-hydroxyecdysone (20E) is a
      physiologically active molecule. In nondiapause eggs, 20E is produced by the
      conversion of maternal conjugated ecdysteroids (ecdysteroid-phosphates) and by de
      novo biosynthesis. In contrast, in diapause eggs, neither of these metabolic
      processes occurs. In de novo biosynthesis of 20E in B. mori eggs, hydroxylation
      at the C-20 position of ecdysone, which is catalyzed by ecdysone 20-hydroxylase,
      is a rate-limiting step. Furthermore, we found that a novel enzyme, called
      ecdysteroid-phosphate phosphatase (EPPase), specifically catalyzes the conversion
      of ecdysteroid-phosphates to free ecdysteroids. The developmental changes in the
      expression pattern of EPPase mRNA correspond closely to changes in the enzyme
      activity and in the amounts of free ecdysteroids in eggs. EPPase is localized in
      the cytosol of yolk cells, and the bulk of maternal ecdysteroid-phosphates is
      bound to vitellin and stored in yolk granules. The vitellin-bound ecdysteroid
      phosphates are scarcely hydrolyzed by EPPase. Therefore, to examine how
      ecdysteroid-phosphates are hydrolyzed by EPPase during embryonic development
      further investigations were focused on yolk granules. Recent data indicate that
      acidification in yolk granules, induced by vacuolar H(+)-ATPase, triggers the
      dissociation of ecdysteroid-phosphates from the vitellin-ecdysteroid-phosphates
      complex and the dissociated ecdysteroid-phosphates are released from yolk
      granules to the cytosol. To explain the process of the increase in the level of
      20E during embryonic development in B. mori eggs, a possible model is proposed.

PMID- 15170052
TI  - Giant malignant fibrous histiocytoma of the pleura arising from solitary fibrous
      tumour.

PMID- 15170057
TI  - The development of the enteropneust hemichordate Balanoglossus misakiensis
      KUWANO.
AB  - We describe development from fertilization to metamorphosis of the enteropneust
      hemichordate Balanoglossus misakiensis. This is the first report to describe the
      complete development of an indirect-developing hemichordate under laboratory
      conditions. Mature adults were induced to spawn by shifting the temperature of
      seawater from 23 to 28 degrees C. Eggs (200 microm diameter) were enclosed within
      a non-mucilaginous membrane, and dispersed readily in seawater. After artificial
      insemination, a fertilization envelope was elevated from the egg surface beneath
      the egg membrane; this was followed by the formation of the first and second
      polar bodies within the envelope. Zygotes cleaved at 20-min intervals to form
      blastulae, and gastrulation started 9 h after fertilization. Embryos hatched 1
      day after fertilization to become typical feeding tornaria larvae. The larvae
      metamorphosed 7-10 days after fertilization without undergoing the first (Muller)
      or forth (Krohn) stage of indirect-developing hemichordate development. Larvae
      that were not fed failed to metamorphose. Juveniles completed adult body
      formation within a week of settling in sand at the bottom of the culture tube. We
      discuss heterochronical modifications of B. misakiensis development, and make the
      case for this species as a potential model organism for the investigation of
      indirect-developing hemichordates.

PMID- 15170060
TI  - Serum 17,20 beta-dihydroxy-4-pregnen-3-one Levels in pregnant and non-pregnant
      female rockfish, Sebastes schlegeli, viviparous teleost, and its production by
      post-ovulatory follicles.
AB  - Changes in serum 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-DP)
      levels around the gestation time of normal pregnant and experimentally non
      pregnant females were investigated in the black rockfish, Sebastes schlegeli, a
      viviparous teleost. The serum 17,20 beta-DP in both females showed similar
      changes and levels, increasing from the early to late gestation periods and
      declining just before parturition in pregnant females and egg-release in non
      pregnant females, respectively. These results suggest that the maintenance of
      high serum levels of 17,20 beta-DP after oocyte maturation is not correlated with
      gestation or parturition, but occurs spontaneously in this species. The decline
      of 17,20 beta-DP levels prior to egg-release in non-pregnant females tended to
      occur one week earlier than those prior to parturition in pregnant females,
      suggesting that both a decline in 17,20 beta-DP levels in mothers and some
      response from embryos are needed for a smooth parturition. The post-ovulatory
      follicles were maintained throughout the gestation period and produced a
      considerable amount of 17,20 beta-DP in vitro (3.44-6.96 pg/ml/mg tissue), but
      little estradiol-17beta (0.92-1.66 pg/ml/mg tissue). The production of 17,20 beta
      DP tended to be enhanced by the addition of a precursor steroid, pregnenolone, in
      the pre-, early and mid-gestation periods. These results strongly suggest that
      the follicle cells in black rockfish have the ability to synthesize 17,20 beta-DP
      during the post-ovulatory period, and high serum 17,20 beta-DP during gestation
      is supplied by the post-ovulatory follicles, which in Sebastes are considered to
      be functionally homologous to the mammalian corpus luteum.

PMID- 15170058
TI  - Retionic acid and its receptors are required for expression of aryl hydrocarbon
      receptor mRNA and embryonic development of blood vessel and bone in the medaka
      fish, Oryzias latipes.
AB  - Retinoic acid (RA), the active derivative of vitamin A, is essential for normal
      embryonic development of vertebrates because both the lack and excess of RA
      result in developmental malformations. We previously reported that aryl
      hydrocarbon receptor (AHR) is also required for vascular and bone formation by
      regulating cytochrome P450 expression. However, little is known about the roles
      of retinoic acid receptors (RAR) and retinoid X receptors (RXR) in the embryonic
      development of blood vessels and molecular cross-talk between RAR/RXR and AHR. We
      report for the first time that RA and RAR/RXR are required for expression of AHR
      mRNA and the embryonic development of blood vessel and bone. The embryonic
      organogenesis of medaka fish was specifically inhibited by an inhibitor of RA
      synthesis (diethylaminobenzaldehyde), antagonists of RAR (Ro41-5253) and RXR
      (Ro71-4595), agonist (beta-naphthoflavone) and antagonist (alpha-naphthoflavone)
      of AHR, and excess RA. These reagents are useful for future studies to elucidate
      molecular mechanisms for vascular and bone formation in the medaka embryogenesis.
      Our results also show that medaka embryos may be useful for screening inhibitors
      of vascular formation for anti-cancer drugs.

PMID- 15170059
TI  - Cellular features of an apoptotic form of programmed cell death during the
      development of the ascidian, Boltenia villosa.
AB  - The phylogenetic position of ascidians near the base of the chordate tree makes
      them ideal organisms for evolutionary developmental studies of programmed cell
      death (PCD). In the present study, the following key features of an apoptotic
      form of PCD are described in Boltenia villosa: fragmentation of DNA, increases in
      plasma membrane permeability, decreases in mitochondrial activity, production of
      reactive oxygen species (ROS), and caspase activation. First, evidence is
      presented for apoptosis of cells within the ovary. Later in development, during
      the early phase of larval tail resorption at the beginning of metamorphosis, some
      notochord nuclei showed DNA fragmentation and their cell corpses were rapidly
      eliminated from the larval body. In striking contrast to the rapid demise of
      notochord cells, larval muscle cells persisted for more than a week within
      developing juveniles. Rhodamine 123 and MTT experiments suggest that mitochondria
      within some of the resorbed larval tail muscle cells were metabolically active
      for more than a week. Furthermore, resorbed tail muscle cells contained a muscle
      specific intermediate filament, termed p58, despite relatively high levels of ROS
      activity and the ubiquitination of their plasma membranes at day two. Corpses of
      larval tail muscle cells containing aggregated pigment granules survived within
      juveniles for more than a month, in contrast to the rapid elimination of
      notochord cells. Evidence consistent with the formation of larval muscle cell
      apoptotic bodies is presented. The most surprising result of the present study
      was that caspase-8, usually associated with apoptotic signaling, was activated in
      larval endoderm cells that develop into adult structures. When the present
      results were compared to features of PCD previously reported in other ascidians,
      significant species differences in PCD were revealed.

PMID- 15170061
TI  - Photoperiodic response of serotonin- and galanin-immunoreactive neurons of the
      paraventricular organ and infundibular nucleus in Japanese quail, Coturnix
      coturnix japonica.
AB  - We investigated the photoperiodic response of serotonin- and galanin (GA)-
      immunoreactive (ir) cells in the paraventricular organ (PVO) and infundibular
      nucleus (IF) of the Japanese quail and the interaction of these cells with
      gonadotropin-releasing hormone (GnRH)-ir neurons in the hypothalamus. Serotonin
      ir cells were located in series from the PVO to the IF, and were connected with
      each other. The number of serotonin-ir cells differed significantly between light
      and dark phases on the short days (SD), but did not differ between light and dark
      phases on long days (LD). GA-ir cells were also found in the PVO and IF. The
      number of GA-ir cells under SD conditions was significantly greater than under LD
      conditions but did not change diurnally. Both serotonin-ir and GA-ir fibers ran
      along the GnRH-ir cells in the nucleus commissurae pallii. Serotonin-ir and GA-ir
      fibers were connected with the GnRH-ir fibers in the external layer of the median
      eminence (ME). We confirmed that GA-ir fibers were closely associated with
      serotonin-ir neurons in the PVO and IF. GA-ir neurons have at least 2 routes of
      regulating GnRH neurons directly, and indirectly via the serotonin-ir cells in
      the PVO and IF.

PMID- 15170062
TI  - Soldier-like intercastes in the rotten-wood termite Hodotermopsis sjostedti
      (Isoptera: Termopsidae).
AB  - All termite species possess a distinct sterile-soldier caste in their colonies,
      although reproductive soldiers, with soldier characteristics and reproductive
      ability, have been reported from several species of the family Termopsidae. Such
      intercastes have been considered the primitive-soldier caste, and based on this
      many researchers have discussed the evolutionary origin of termite soldiers. We
      investigated whether such soldier-reproductive intercastes also exist in the
      Japanese rotten-wood termite Hodotermopsis sjostedti. Abnormal individuals with
      soldier-like characteristics were found and designated as soldier-like
      intercastes, which appeared to have both soldier and reproductive
      characteristics. Based on our morphometric analyses and histological
      examinations, we suggest that the developmental origin of this intercaste is a
      pseudergate, nymph or sixth-instar larva. In addition, the intercaste was found
      to have relatively well-developed gonads, although mature oocytes and spermatozoa
      were not found in female ovaries and male seminal vesicles, respectively. We
      conclude that the soldier-like intercaste of H. sjostedti does not have
      reproductive ability, which is different from all other known soldier-like
      intercastes in Termopsidae.

PMID- 15170063
TI  - Absence of the functional Myosin heavy chain 2b isoform in equine skeletal
      muscles.
AB  - Nucleotide sequences which included the full coding region for three types of
      myosin heavy chain (MyHC) isoforms were determined from equine skeletal muscles.
      The deduced amino acid sequences were 1937, 1938, and 1935 residues for the MyHC
      2a, -2x, and -slow, respectively. No MyHC-2b isoform was amplified from the
      equine muscle cDNA except for one pseudogene fragment. One nucleotide was
      inserted in the coding region of the equine pseudogene product, a minute amount
      of which was expressed in the skeletal muscle. The 596 bp sequence of the equine
      MyHC pseudogene was categorized into the MyHC-2b genes on the phylogenetic tree
      of the mammalian MyHC genes. These results suggest that an ancestral MyHC-2b gene
      had lost its function and changed to a pseudogene during the course of horse
      history. The MyHC genes in some ungulates were analyzed through the PCR
      amplifications using the MyHC isoform-specific primers to confirm the presence of
      the MyHC-2b and -2x genes. The exon coding the 3' untranslated region of the MyHC
      2x was successfully amplified from the all ungulates examined; however, that of
      the MyHC-2b gene was amplified only from horses, pigs and lesser mouse deer. The
      PCR analyses from rhinoceros, sika deer, moose, giraffes, water buffalo, bovine,
      Japanese serow and sheep genes implied the absence of the MyHC-2b-specific
      sequence in their genomes. These results suggest that the MyHC-2b gene
      independently lost its function in some ungulate species.

PMID- 15170065
TI  - Renal sodium handling for body fluid maintenance and blood pressure regulation.
AB  - Renal sodium handling is an essential physiologic function in mammal for body
      fluid maintenance and blood pressure regulation. Recent advances in molecular
      biology have led to the identification of kidney-specific sodium transporters in
      the renal tubule, thereby supplying vast information for renal physiology as well
      as systemic physiology. Renal urinary concentration for body fluid maintenance is
      accomplished by counter current multiplication in the distal tubule. Sodium
      transport in the thick ascending limb of Henle (TAL) is the initial process of
      this system. We have demonstrated that renal urinary concentration is regulated
      in part by the expression of the Na(+)-K(+)-2Cl(-) co-transporter (BSC1) in TAL,
      by showing two mechanisms of BSC1 expression: pitressin vasopressin (AVP)
      dependent and AVP-independent mechanisms. Two additional findings, namely, a lack
      of the ability to increase BSC1 expression leads to urinary concentrating defect
      and an enhanced BSC1 expression underlies the edema-forming condition, confirm
      the close association between sodium handling in TAL and body fluid accumulation.
      The lines of evidence from our genetic studies of the general Japanese population
      suggest the importance of mendelian hypertension genes in the genetic
      investigation of essential hypertension. Because those genes directly or
      indirectly regulate sodium transport by the Na-Cl co-transporter or the
      epithelial sodium channel in the distal convoluted tubule to the collecting duct
      (distal tubular segments after TAL), sodium handling in this part of the renal
      tubule may be, at least in part, involved in blood pressure regulation. The
      unveiling of such physiologic roles of sodium handling based on the sodium
      transporters or on the tubular segments may lead to a better understanding of
      systemic physiology as well as to the development of novel therapy for body fluid
      or blood pressure disorders.

PMID- 15170066
TI  - [Development of radical reactions in water aimed at environmentally benign
      synthetic reactions].
AB  - The aqueous medium radical reactions of a variety of imine derivatives such as
      oxime ether, oxime, hydrazone, nitrone, and N-sulfonylimine were investigated.
      Triethylborane-mediated intermolecular alkyl radical addition to glyoxylic oxime
      ether, oxime, and nitrone in water proceeded smoothly to give alpha-amino acid
      derivatives in good yields. Alkyl radical addition to N-sulfonylimine proceeded
      in aqueous media using zinc as a radical initiator. The zinc-mediated radical
      reaction of the hydrazone with a chiral camphorsultam provided the corresponding
      alkylated products with good diastereoselectivities, which could be converted
      into enantiomerically pure alpha-amino acids. The indium-mediated radical
      reactions provide new opportunities for carbon-carbon bond formation such as
      alkylation reactions of imines and 1,4-addition to electron-deficient olefins.
      The indium-mediated tandem reactions also proceeded effectively via two carbon
      carbon bond-forming processes for the preparation of various types of
      functionalized cyclic compounds.

PMID- 15170068
TI  - [Enantiomeric determination of ephedrine derivatives in unregulated drugs using
      capillary electrophoresis].
AB  - Capillary electrophoresis (CE) was applied to enantiomeric separation of chiral
      ephedrine derivatives (d/l-ephedrine, d/l-methylephedrine, d/l-pseudoephedrine,
      and d/l-norephedrine) in unregulated drug products. Unregulated drugs, referred
      to as dietary supplements in U.S.A., have been used legally as tonic agents, but
      illegal substances such as ephedrine were often detected. Baseline separation of
      all enantiomers of ephedrine derivatives was achieved using an electrophoretic
      solution containing heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DM-CD) as a
      chiral selector. The optimal conditions were established to be: capillary column
      of fused silica (50 microm i.d. x 56 cm); running buffer of 20 mM DM-CD with 50
      mM potassium dihydrogenphosphate background electrolyte, pH 2.6; capillary
      temperature of 20 degrees C; applied voltage of 30 kV; on-column detection at 195
      nm; and injection pressure of 50 mbar x 3 s. Under these conditions, all four
      pairs of enantiomers were sufficiently resolved, and eight peaks were observed
      with resolution factors of greater than 1.5. The calibration curves of all
      enantiomers showed good linearity over the concentration range of 2.5-10
      microg/ml (r =0.999). The present method was used in a survey of marketed
      products. The resultant chiral contents were reported and the analytical data
      were also compared with those from HPLC. This method is useful in the simple and
      rapid analysis of ephedrine derivatives in marketed products.

PMID- 15170064
TI  - [Analysis and its application for prevention of side-effects of drugs and for
      evaluation of drug responsiveness].
AB  - The response of patients to drugs can be affected by genetic
      polymorphisms/defects in drug metabolizing enzymes, transporters, and receptors.
      Genetic polymorphisms/defects are generated by mutation of coding regions and/or
      noncoding regions of target genes, such as single-point mutations,
      deletions/insertions, variation in the number of tandem repeats, etc. If a
      genetic defect in a patient which affects drug response were known, it would be
      possible to optimize medications individually. The author developed two improved
      methods for detecting CYP2C19(*)2 and CYP2C19(*)3. Using the methods, the type of
      CYP2C19 gene was examined in 80 inpatients, and the medication status of patients
      with the mutation was examined focusing on dosage and side effects. The author
      also examined polymorphisms of the serotonin transporter/biosynthetic or
      metabolizing enzymes in depressive patients treated with fluvoxamine, a selective
      serotonin reuptake inhibitor, and the relationship between clinical efficacy and
      polymorphisms was investigated. As a result, patients with the S/S genotype of 5
      HTTLPR were found to experience better clinical efficacy.

PMID- 15170067
TI  - Studies on the effectiveness and safety of cilostazol, beraprost sodium,
      prostaglandin E1 for the treatment of intermittent claudication.
AB  - To study the effectiveness for the treatment of intermittent claudication (IC) of
      three drugs with antiplatelet effects, cilostazol, beraprost sodium, and
      prostaglandin E(1) (PGE(1)), by using a systemic review of literature and a meta
      analysis. A search was undertaken for studies reported between 1966-2002 in the
      MEDLINE database, and references in published articles and reviews were obtained.
      Data for maximum walking distance (MWD), pain-free walking distance (PFWD), and
      adverse clinical events were extracted from the articles that met the inclusion
      criteria. The pooled estimates of the weighted mean differences (WMD) of MWD and
      PFWD for cilostazol were 52.19 m [95% confidence interval (CI) 32.08, 72.31] and
      39.75 m [95% CI 23.39, 56.10], and those for PGE(1) were 100.27 m [95% CI 15.76,
      184.78] and 55.73 [95% CI 21.54, 89.92], respectively. These differences were
      statistically significant between the test drugs and placebo. However there was
      no statistical significance difference between beraprost sodium and placebo, even
      though there was one study that showed a tendency for improvement in walking
      distance. The total rate of adverse clinical events in cilostazol and beraprost
      sodium was higher than that for placebo, while there was no statistical
      significant difference between PGE(1) and placebo, although PGE(1) had a higher
      tendency for adverse clinical events. The literature evaluation results and the
      meta-analysis suggest that these two drugs (cilostazol and PGE(1)) can be
      considered to be effective drugs for the treatment of IC. Due to current
      availability of only a few clinical reports, further studies are needed to
      clarify the efficacy of beraprost sodium in the treatment of IC.

PMID- 15170069
TI  - Objective evaluation of generic drug information.
AB  - Pharmacists active in health care venues need to be able to evaluate generic
      drugs in terms of effectiveness, safety, and economy to ensure that they are used
      appropriately. As part of the ongoing study of these factors, we carried out an
      objective evaluation of information provided for generics. A minimum of 20
      commercially available products was considered for each pharmaceutical
      ingredient. The information subjected to evaluation consisted of the text of drug
      package inserts and information noted on interview forms. Using our own criteria
      for evaluating drug information, we attempted to quantify the amounts of
      information provided. Then, based on the numerical values obtained, we calculated
      information quantities with reference to drug prices to study the relationship
      between prices and available information for original drugs and their later
      developed, generic equivalents. A total of 14 different pharmaceutical
      ingredients (327 product items) were considered, with the information quantity
      for generics amounting to 27.9+/-17.8-46.3+/-21.4% (Mean+/-S.D.) that for the
      original drugs. Examined on the basis of individual pharmaceutical companies, the
      corresponding ratio came to 15.1+/-7.8-62.4+/-6.4% (Mean+/-S.D.). For generics,
      the relationship between drug price (expressed against a value of 1.0 for
      original drugs) and information quantity (Qua(i)) came to 0.79+/-0.46-1.90+/
      0.79% (Mean+/-S.D.). These results clearly point to the importance of evaluating
      information quantity for generic drugs on a maker-by-maker basis.

PMID- 15170070
TI  - [Pharmacological effects of Daphne genkwa and Chinese medical prescription, "Jyu
      So-To"].
AB  - Daphne genkwa (Thymelaeaceae) has been used as a folk medicine in China. We
      investigated the effects of D. genkwa and Jyu-So-To on various pharmacologic
      models in mice including the azoxymethane (AOM)-induced colonic aberrant crypt
      focus formation assay, ornithine decarboxylase (ODC) activity assay, and two
      types of mouse ear swelling model. Administration of 236.3 ppm of Jyu-So-To in
      drinking water significantly suppressed AOM-induced colonic aberrant crypt focus
      formation (p < 0.05), with an inhibitory ratio of 46.7%. The effects of several
      extracts with organic solvents of D. genkwa on murine epidermal ODC activity were
      examined. In particular, the inhibitory ratio of the n-hexane extract was 30.8%.
      In the 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model in
      mice, the methanol extract resulted in 56.3% inhibition compared with the
      control. On the other hand, there are two peaks of responses at 1 h (immediate
      phase reaction; IPR) and 24 h (late-phase reaction) in biphasic cutaneous
      reactions, which are enhanced in the dinitrofluorobenzene model (DNFB). The water
      extract of D. genkwa clearly inhibited the IPR ear swelling. These results
      suggest that D. genkwa and Jyu-So-To should be a promising source of antitumor,
      antiinflammatory, and antiallergy agents.

PMID- 15170071
TI  - [Practice for promoting proper use of reusing the leftover medicines in the
      outpatients of the chronic disease].
AB  - Cooperating with hospitals and clinics, the current situation of leftover
      medicines for outpatients was investigated. Pharmacies played a role in receiving
      and counting leftover medicines. Pharmacists reported the number of leftover
      medicines to physicians and facilitated a decrease in the dosing days of
      prescriptions for the purpose of reusing leftover medicines. Our study, conducted
      from March 2003 to July 2003 in three pharmacies, found that the saved drug cost
      and pharmacist technical fees was 489830 yen. There was an income decrease of
      69080 yen to the pharmacies. If, as we found in our study, an average medication
      savings of 40000 yen per pharmacy-month represents a conservative estimate, the
      total national cost due to medication saving would nearly 20 billion yen per
      year. The rate of forgetting to take medicine rose as the dosing frequency
      increased. With a dose of three times a day before every meal, the forgetting
      probability was 100%.

PMID- 15170072
TI  - [Effect of Kampo medicines on the peripheral blood flow rate of betamethason
      induced Oketsu syndrome mice by laser Doppler flow meter].
AB  - Stagnation of peripheral blood flow is the cause of various diseases. Changes in
      peripheral blood flow after oral administration of Kampo medicines in mice with
      betamethasone-induced oketsu syndrome and normal mice were examined using a laser
      Doppler blood flow meter. The Kampo medicines used were: Toki-shakuyaku-san; Kami
      shoyo-san; Keishi-bukuryo-gan; Daio-botanpi-to; Tokaku-joki-to; Goshuyu-to; and
      Hange-koboku-to. In the oketsu mice, blood flow was improved by single-dose
      administration of Toki-shakuyaku-san, Kami-shoyo-san, Keishi-bukuryo-gan, Daio
      botanpi-to, Tokaku-joki-to, and Goshuyu-to, but only Toki-shakuyaku-san increased
      blood flow significantly in normal mice. In addition, blood flow decreased after
      single-dose administration of Keishi-bukuryo-gan, Daio-botanpi-to, and Tokaku
      joki-to in normal mice.

PMID- 15170073
TI  - Flow-induced endothelium-dependent vasoreactivity in rat mesenteric arterial bed.
AB  - We studied rat mesenteric arterial beds to determine the relationship between the
      effects of flow-induced shear stress and agonists on mesenteric vasoreactivity.
      When beds were perfused at gradually increasing flow rates, perfusion pressure
      was flow rate-dependently increased. The flow rate-mediated increase in perfusion
      pressure was significantly enhanced by N(G)-nitro-L-arginine (L-NOARG) plus
      methylene blue (MB) and slightly enhanced by treatment with tetraethylammonium
      (TEA). In the presence of L-NOARG, MB, TEA, and indomethacin, the flow rate
      induced increase in perfusion pressure was significantly enhanced, but this
      enhancement was significantly inhibited by combined treatment with BQ-123 plus BQ
      788 (ET(A)- and ET(B)- receptor antagonists, respectively). The ET-1 content of
      the perfusate was significantly increased following combined pretreatment with L
      NOARG, MB, TEA, and indomethacin at a high flow rate. The methoxamine-induced
      contraction was significantly enhanced by NOS inhibition in both high- and low-
      flow-treated groups. The released nitrite level was significantly greater in high
      flow-loaded than in the low-flow-loaded beds. We conclude that in this model, the
      response of vascular tone to flow stimulation is subtly regulated by endothelium
      derived factors (especially, NO, endothelium-derived hyperpolarizing factor, and
      ET-1), and that these factors interact with each other.

PMID- 15170074
TI  - Spectral analysis of colonic intraluminal pressure in patients who received a
      colonic replacement following radical esophagectomy.
AB  - The aim of this study was to evaluate the motor activity of the interposed
      colonic segment in patients who had received a colonic replacement following
      radical esophagectomy using spectral analysis and a 24 hr activity graph. The 24
      hr ambulatory pressure waves were recorded in the replaced colon after
      esophagectomy (n=8) using a solid-state manometric catheter (MicroDigitrapper,
      Synetics). Motility and spectral analyses of the intraluminal pressure waves were
      performed by Multigram and Gastrosoft (Synetics). It was revealed that after a
      meal the 3 cpm (cycles per minute) component of the motility index increased but
      the 12-15 cpm component decreased. The diurnal rhythm showed that colonic
      motility was high in the daytime and low during sleep. In contrast, duodenal
      motility was relatively high even during sleep. The motility index increased as
      the postoperative period increased. The motility of the replaced colon was higher
      during the daytime and after meals. The higher motility after meals was
      characterized by an increase in the 3 cpm component. These motor characteristics
      may help the function of the replaced colon as a substitute for the esophagus.

PMID- 15170075
TI  - TNF-alpha augments the expression of RhoA in the rat bronchus.
AB  - While nonspecific airway hyperresponsiveness (AHR) is a central feature of
      allergic bronchial asthma, the mechanism underlying the development of AHR is not
      clearly understood. We have previously demonstrated in vitro hyperresponsiveness
      of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively
      sensitized and repeatedly challenged with aerosolized antigen. It has also been
      demonstrated that the ACh-induced, RhoA-mediated Ca(2+) sensitization is markedly
      augmented concomitantly with an increased expression and activation of RhoA
      protein in the bronchial smooth muscle of the antigen-treated rats. In the
      present study, we have investigated whether TNF-alpha, a proinflammatory cytokine
      which is involved in bronchial asthma, causes upregulation of RhoA mRNA and
      protein in the rat bronchus. Treatment of rat bronchial smooth muscle
      preparations with TNF-alpha (300 ng/ml for 24 hr) significantly shifted the
      concentration-response curve to ACh upwards, but did not alter the response to
      high K(+), when compared to that of control tissues. Levels of RhoA mRNA and
      protein in the TNF-alpha-treated bronchus were significantly greater than those
      in the control group. In conclusion, it is suggested that the augmentation of the
      ACh-induced contractile response evoked by TNF-alpha might be mediated by an
      upregulation of RhoA in rat bronchial smooth muscle.

PMID- 15170076
TI  - KB-R7943 reveals possible involvement of Na(+)-Ca2+ exchanger in elevation of
      intracellular Ca2+ in rat carotid arterial myocytes.
AB  - A Na(+)/Ca(2+) exchanger (NCX) is one of the major regulators of intracellular
      Ca(2+) concentration ([Ca(2+)](i)) in cardiac muscle cells. Although vascular
      smooth muscle myocytes also express NCX proteins, their functional role has not
      been clear, mainly due to the lack of specific inhibitors of NCX and relatively
      low levels of expression of NCX. In the present study, we have examined the
      involvement of NCX in the Na(+) deficient (0 Na(+)) elevation of [Ca(2+)](i) in
      rat carotid arterial myocytes using KB-R7943, an inhibitor of NCX. Perfusion with
      a Na(+)-free bathing solution, prepared by replacement of Na(+) with N-methyl-D
      glucamine, induced an elevation of [Ca(2+)](i), which was effectively inhibited
      by KB-R7943 (IC(50)=3.5 microM). This inhibition was reversed by washout of KB
      R7943. In contrast, D600, a blocker of voltage dependent L-type Ca(2+) channels
      (VDCC), did not affect the 0 Na(+)-induced elevation of [Ca(2+)](i). Treatment of
      myocytes with ryanodine abolished the elevation of [Ca(2+)](i) caused by caffeine
      but not that caused by 0 Na(+). Application of Cd(2+), which is known to block
      NCX as well as VDCC, also significantly inhibited the 0 Na(+) induced elevation.
      These results suggest that KB-R7943 inhibits the extracellular Na(+) dependent
      ([Na(+)](o)) change in [Ca(2+)](i) in rat carotid arterial myocytes, which is
      presumably activated by the reverse mode of NCX.

PMID- 15170078
TI  - [Regulation by astrocytic ATP of synaptic transmission].
AB  - Originally ascribed to having only passive roles in the CNS, astrocytes are now
      known to have an active role in the regulation of synaptic transmission. Neuronal
      activity can evoke Ca(2+) transients in astrocytes and Ca(2+) transients in
      astrocytes can evoke changes in neuronal activity. The excitatory
      neurotransmitter glutamate has been shown to mediate such bi-directional
      communication between astrocytes and neurons. We demonstrate here that ATP, a
      primary mediator of intercellular Ca(2+) signaling among astrocytes, also
      mediates intercellular signaling between astrocytes and neurons in hippocampal
      cultures. Mechanical stimulation of astrocytes evoked Ca(2+) waves mediated by
      the release of ATP and activation of P2 receptors. Mechanically evoked Ca(2+)
      waves led to decreased excitatory glutamatergic synaptic transmission in an ATP
      dependent manner. Exogenous application of ATP does not affect post-synaptic
      glutamatergic responses but decreased pre-synaptic exocytotic events. Finally, we
      show that astrocytes exhibit spontaneous Ca(2+) oscillations mediated by
      extracellular ATP and that inhibition of these Ca(2+) responses enhanced
      excitatory glutamatergic transmission. We therefore conclude that ATP released
      from astrocytes exerts tonic and activity-dependent down-regulation of synaptic
      transmission via pre-synaptic mechanisms.

PMID- 15170077
TI  - [The mechanism of ATP release as an autocrine/paracrine molecule].
AB  - Many studies have been performed to clarify the underlying mechanisms of the
      release of ATP as an autocrine / paracrine signaling molecule. So far, there is a
      variety of findings on the mode of release of this nucleotide. This review
      focused on the possible mechanisms of ATP release. The ATP binding cassette,
      especially CFTR (cystic fibrosis transmembrane conductance regulator), is a
      strong candidate for a channel or a transporter for outward movement of ATP.
      CFTR, which is activated via phosphorylation by protein kinase A, causes an
      opening of channels for Cl(-) and ATP(4-), releasing ATP. However, the possible
      involvement of CFTR in ATP release is still under dispute. As another candidate
      of the membrane machinery, the hemichannel of gap junction has been raised.
      Mechanical stress and photoliberation of caged InsP(3) induce the release of ATP
      as a paracrine through the hemichannel accompanied with the increase of
      [Ca(2+)]i. These events result in the Ca(2+)wave as cell-to-cell communications.
      In conclusion, an authoritative view of the mechanism of ATP release remains to
      be made clear in future studies.

PMID- 15170079
TI  - [Extracellular ATP mediated mechano-signaling in mammary glands].
AB  - ATP, an important and ubiquitous extracellular signaling molecule, is often
      released by mechanical stimuli and plays an essential role in mechano-signaling.
      In lactating mammary glands, secretory epithelial (SE) cells form alveoli in
      which milk is held, and myoepithelial (ME) cells surrounding the alveoli contract
      in response to oxytocin to expel milk. Previously we found that the contraction
      of ME cells worked as a mechanical stress to SE cells and caused ATP-release in
      cultured mammary epithelial cells. The released ATP activated P2Y2 in surrounding
      SE cells and P2Y1 in ME cells. We already reported that ATP synergistically
      enhanced oxytocin response in ME cells. These findings mean that ME and SE cells
      interact mutually via released ATP to enhance the milk ejection. Recently, we
      found that cell-stretch also induced Ca(2+)-increases and ATP-release. The
      stretching of alveoli should occur by milk filling. So, only the milk-filled
      alveoli (but not empty alveoli) are surrounded by ATP. The ATP lowers the
      threshold of the oxytocin receptors and enables the milk-filled alveoli to
      contract in response to oxytocin at a concentration in the blood. Slight but
      apparent constitutive-ATP-release was observed in non-stimulated cells and the
      release was enhanced in Ca(2+)-free solution. The pathway of ATP-release is not
      yet clear, but pharmacologically, there seems to be two or more pathways.

PMID- 15170080
TI  - [ATP release pathways in vascular endothelial cells].
AB  - Vascular endothelial cells regulate vascular tonus, growth, and angiogenesis in
      response to mechanical stresses. ATP release is one of well-known
      mechanosensitive responses in endothelial cells. Released ATP induces Ca(2+)
      responses and nitric oxide production in neighboring cells in an auto/paracrine
      manner. Mechanosensitive and agonist-induced ATP releases are also observed in
      other cell types, but the cellular mechanisms and pathways of ATP release are
      largely unknown. Reported candidates for ATP release pathways are ABC proteins
      including P-glycoprotein and CFTR, exocytosis of ATP-containing vesicles, and ATP
      permeable anion channels. In vascular endothelium, vesicular exocytosis, volume
      regulated anion channels (VRAC), and connexin hemichannels have been reported as
      candidates for ATP release pathways. We found that VRAC inhibitors suppressed
      hypotonic stress-induced ATP release in bovine aortic endothelial cells.
      Furthermore, extracellular ATP suppressed VRAC current in a voltage dependent
      manner, which could be fitted to the permeation-blocker model with a Kd(0) of 1
      mM and delta value of 0.41. However, it should be noted that VRAC is probably not
      the only pathway for ATP release in the endothelium, because basal ATP release
      was not inhibited by VRAC inhibitors. Further investigations are definitely
      warranted to clarify the details and therapeutic significance of mechanosensitive
      ATP release in the endothelium.

PMID- 15170081
TI  - [New method for quantification of cell swelling using infrared differential
      interference microscopy].
AB  - We have developed a novel device for the quantification of swelling of cells in
      acute brain slices. We can also carry out detailed real-time monitoring of
      hippocampal cells. The device we developed is based on an infrared differential
      interference contrast microscopy (IR-DIC) and a custom-made real-time
      computerized image analysis system for the quantification of the morphological
      dynamics of cells in slice preparations. We applied the coefficient of variation
      (CV) of light intensity in IR-DIC images to quantify the change in morphological
      dynamics. There were notable close relationships among the edema formations, the
      light transmittance, extent of changes in CV, and features of fEPSP during
      ischemic insult. We also applied this method for the evaluation of
      neuroprotective effects of mannitol. The dose-dependent improvement on the
      deteriorated hippocampal slices could be obtained by administration of mannitol
      (10, 50, and 100 mM) after 10-min ischemia. The present results indicate that CV
      is a reliable quantification index for edema formation of brain tissue and
      confirm that applying CV for the analysis in addition to the light transmittance
      analysis presents additional important information on brain tissue sweling.

PMID- 15170082
TI  - [Current status and perspectives on the development of therapeutic agents for
      Alzheimer's disease].
AB  - Acetylcholinesterase inhibitors have beneficial effects to improve the cognitive
      impairment in patients with mild to moderate Alzheimer's disease (AD). In
      addition, a channel blocker of N-methyl-D-aspartate receptor, memantine
      hydrochloride, was approved as a therapeutic agent for patients with moderate to
      severe AD in both EU countries in 2002 and USA in 2003, while the clinical
      development is still ongoing in Japan. In contrast, the pharmacotherapy for a
      prime cure against AD is not available in the market, although there has been a
      worldwide search for novel compounds. The most plausible mechanism for the
      treatment of AD is the reduction of the amyloid beta-peptide (Abeta) plaques, one
      of the pathological markers of AD, in the brain. For this purpose, the inhibitors
      of beta-secretase and gamma-secretase, which cleave amyloid precursor protein
      (APP) to release Abeta, has been developed to interfere with APP processing. The
      beta-sheet breaker and metal chelators for the breakdown of aggregated Abeta have
      also been synthesized as well as the immunotherapeutic approach using Abeta
      vaccine. On the other hand, some nonsteroidal anti-inflammatory drugs, such as
      ibuprofen and sulindac, noncompetitively inhibited Abeta production but not Notch
      cleavage. The development of Abeta-lowering drugs is highly expected for the
      treatment of AD.

PMID- 15170083
TI  - [Pharmacological profiles and clinical effects of antiparkinsonian agent,
      pramipexole].
AB  - Pramipexole hydrochloride (pramipexole) is a nonergot dopamine D(2) agonist, and
      the S(-)enantiomer is used for the treatment of Parkinson's disease (PD).
      Pramipexole possessed the highest affinity with the D(3) subtype among the D(2)
      receptor subfamily members (D(2), D(3), D(4)), lacking affinity with the D(1) and
      D(5) subtype. Pramipexole ameliorated the motor disturbances in PD animal models,
      induced contralateral rotational behavior reflecting post-synaptic D(2) receptor
      stimulation in the striatum, and showed a variety of neuroprotective effects in
      vitro and in vivo experimental systems. The neuroprotective effects of
      pramipexole seemed to be derived from several mechanisms: stimulation of D(2)
      autoreceptor, stimulation of D(3) receptor, inhibition of oxidative reaction and
      following radical production, increase of Bcl-2 protein and inhibition of
      apoptotic cell death, and production of neurotrophic factor. Clinical efficacy of
      pramipexole both in monotherapy and combined use with L-DOPA were confirmed
      evaluating by UPDRS (Unified Parkinson's Disease Rating Scale) II (Activities of
      daily living) and III (Motor), in the results of clinical studies mainly
      performed in USA and European countries and partly in Japan. In addition,
      patients initially treated with pramipexole demonstrated reduction in problematic
      symptoms and in loss of striatal [(123)I]2beta-carboxymethoxy-3beta-(4
      idodophenyl)tropan uptake, a marker of dopamine neuron degeneration, compared
      with those initially treated with L-DOPA.

PMID- 15170084
TI  - Assessment of acute myocardial infarction in Japan by the Japanese Coronary
      Intervention Study (JCIS) Group.
AB  - BACKGROUND: Until now, large-scale nationwide surveys of acute myocardial
      infarction (AMI), such as those performed in Europe and America, have not been
      performed in Japan. Therefore, in 2000 the Japanese Coronary Intervention Study
      (JCIS) group conducted a nationwide survey on the incidence of AMI in Japan.
      METHODS AND RESULTS: Questionnaires were collected from 8,268 facilities
      throughout Japan. The total annual number of patients with AMI was 66,459 (52.4
      patients/10(5) population), and the AMI incidence rate in Japan was approximately
      25% of that in the United States. Most facilities with AMI patients treated less
      than 50 AMI patients annually, and that number was 45.0% of total AMI patients.
      The incidence of AMI patients was highest in Kochi, Kumamoto, and Wakayama
      prefectures, and lowest in Yamanashi, Saitama and Shiga prefectures. The ratio of
      the highest incidence to the lowest incidence was 2.0. A significant correlation
      was observed between the mean age of the prefectural population, as a coronary
      risk factor, and the incidence of AMI. CONCLUSIONS: The incidence of AMI in Japan
      is approximately 25% that in the United States and it varies considerably among
      the prefectures, one of the causes being the difference in the mean age. This
      provides important information for assessing the guidelines for Japanese patients
      with AMI.

PMID- 15170086
TI  - Relation between white blood cell counts and myocardial reperfusion in patients
      with recanalized anterior acute myocardial infarction.
AB  - BACKGROUND: The clinical significance of the white blood cell (WBC) count on
      admission in relation to the duration of ischemia in acute myocardial infarction
      (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on
      admission to myocardial reperfusion was examined in 135 patients with
      recanalization of an anterior AMI within 6 h of symptom onset. Patients were
      classified according to the WBC count on admission: Group L (n=75), WBC count
      <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak
      creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a
      myocardial blush grade of 0/1, was more frequent in group H than in group L.
      Among the patients in group H, those with early (<or=3 h) recanalization had a
      lower QRS score before recanalization than those with late (>3 h) recanalization;
      however, peak CK and the incidence of impaired myocardial reperfusion were
      similar in these subgroups of patients. Multivariate analysis showed that WBC
      count >or=12,000 cells/mm(3) on admission was an independent predictor of
      impaired myocardial reperfusion in patients with early recanalization (odds ratio
      7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher
      WBC count may be associated with progression of myocardial damage after
      recanalization in patients with early recanalization of an anterior AMI.

PMID- 15170085
TI  - R353Q polymorphism, activated factor VII, and risk of premature myocardial
      infarction in Japanese men.
AB  - BACKGROUND: The association between myocardial infarction (MI) and the R353Q
      polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII
      concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains
      controversial. METHODS AND RESULTS: The present case - control study in 127
      Japanese men with their first MI at or before 45 years of age and 150 matched
      healthy controls was designed to clarify this association in premature MI. R353Q
      polymorphism was determined by polymerase chain reaction, and plasma
      concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ,
      and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the
      patients, and 131, 17, and 2 in the controls. The Q allele was negatively
      associated with premature MI (odds ratio =0.41, p=0.038). The plasma
      concentration of FVIIa was slightly higher in patients (55.1+/-40.9 U/L) than in
      controls (44.8+/-20.2 U/L), but not significantly (p=0.078); the plasma
      concentration of FVIIag did not differ between patients (88.7+/-15.7%) and
      controls (87.0+/-9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by
      R353Q polymorphism (p<0.001). CONCLUSIONS: The Q allele may be protective against
      premature MI.

PMID- 15170088
TI  - Aortic calcification detected in a mass chest screening program using a mobile
      helical computed tomography unit. Relationship to risk factors and coronary
      artery disease.
AB  - BACKGROUND: There is a significant relationship between calcification of the
      aortic arch (Arch) detected by chest X-ray examination and coronary artery
      disease (CAD), but the relationship between risk factors, CAD and aortic
      calcification detected during a mass screening program using a mobile helical
      computed tomography (CT) unit remains unknown. METHODS AND RESULTS: In total
      2,623 subjects (1,347 men, and 1,276 women; mean age, 52.9+/-13.8) underwent an
      examination for lung cancer and tuberculosis using a mobile helical CT unit. The
      frequency of calcification was 19.6% in the Arch, 2.7% in the ascending aorta,
      and 10.1% in the descending aorta, values that were positively associated with
      age in both genders. Hypertension and smoking were significantly related to
      calcification of the thoracic aorta. There was a significant relationship between
      CAD and aortic calcification. The odds ratio of aortic calcification for patients
      with CAD increased as the number of calcified segments increased. CONCLUSIONS:
      These results suggest that detection of calcification in the thoracic aorta
      during a mass chest screening using a mobile helical CT unit can be used to
      evaluate the risk of CAD.

PMID- 15170087
TI  - Three-year clinical follow-up results of intracoronary radiation therapy using a
      rhenium-188-diethylene-triamine-penta-acetic-acid-filled balloon system.
AB  - BACKGROUND: Intracoronary radiation therapy (IRT) prevents recurrent in-stent
      restenosis, but its long-term safety and efficacy remain uncertain. In the
      present study, the long-term clinical outcome of IRT using the rhenium-188
      ((188)Re)-filled balloon system was evaluated. METHODS AND RESULTS: After
      successful catheter-based treatment of either a de novo or restenotic lesion, 187
      patients were randomly assigned to either the radiation (N=104) or the control
      (N=83) group. The (188)Re-filled balloon system was designed to deliver 17.6 Gy
      to 1.0-mm tissue depth. Angiographic restenosis was significantly reduced with
      IRT at 9 months (18.9% vs 45.9%, p<0.001), but the incidence of major adverse
      cardiac events (MACE) including death, myocardial infarction, and target-vessel
      revascularization (TVR) by 3 years showed no difference. Lack of clinical benefit
      might be related to TVR caused by geographic miss (6/22, 28.6%), balloon-induced
      unhealed dissection (3/22, 13.6%) and late thrombosis (2/22, 9.1%). In the
      restenotic subgroup (N=39), the MACE rate within 3 years was significantly
      reduced with IRT (14.3% vs 54.5%, p=0.01). CONCLUSIONS: IRT using the (188)Re 
      filled balloon system is safe and technically feasible. Although IRT failed to
      show favorable outcomes for de novo lesion, the clinical benefits for restenotic
      lesions seem durable for 3 years. Furthermore, preventing geographic miss and
      dissection might improve long-term outcomes.

PMID- 15170089
TI  - Low serum alpha-tocopherol concentrations in subjects with various coronary risk
      factors.
AB  - BACKGROUND: Oxidative stress may play an important role in the genesis and
      development of atherosclerosis. METHODS AND RESULTS: To examine whether oxidative
      stress is increased in the presence of various coronary risk factors, serum alpha
      tocopherol concentrations were determined in 168 apparently healthy subjects
      recruited from Daioh town (73 men and 95 women, mean age: 42+/-11 years). The
      alpha-tocopherol concentration (mg/g lipids) was significantly lower in men,
      older subjects (>or=50 years of age), smokers, those with hyper-low density
      lipoprotein (LDL)-cholesterolemia (C) (>or=160 mg/dl), hypertriglyceridemia (TG)
      (>or=150 mg/dl), hypo-high density lipoprotein (HDL)-C (<40 mg/dl), fasting
      hyperglycemia (>110 mg/dl) and obesity (body mass index >or=25 kg/m (2)) than in
      women, younger subjects, nonsmokers, those with normoLDL-C, normoTG, normoHDL-C,
      fasting normoglycemia and the non-obese. The concentration was not significantly
      different between hypertensives and nonhypertensives. Multivariate logistic
      regression analysis showed that the adjusted odds ratios (95% confidence
      interval) for hyperTG and hypoHDL-C as a factor for the lowest tertile of alpha
      tocopherol concentration were 6.2 (1.6-24.4, p<0.01) and 6.0 (1.5-22.6, p<0.01),
      and those of the other risk factors were not significant. The alpha-tocopherol
      concentrations were significantly positively correlated with HDL-C concentrations
      (R=0.53) and negatively with TG concentrations (R=-0.53), BMI (R=-0.35), LDL-C
      concentrations (R=-0.25) and age (R=-0.22). CONCLUSION: Increased oxidative
      stress, as shown by decreased alpha-tocopherol concentrations, was linked to the
      presence of various coronary risk factors, among which hyperTG and hypoHDL-C
      appeared to be most heavily associated with oxidative stress.

PMID- 15170090
TI  - Diagnostic value of 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP)
      single photon emission computed tomography (SPECT) in patients with chest pain.
      Comparison with rest-stress 99mTc-tetrofosmin SPECT and coronary angiography.
AB  - BACKGROUND: Basic and clinical studies have indicated that 15-(p-[(123)I]
      iodophenyl)-3-(R, S) methylpentadecanoic acid (BMIPP) single photon emission
      computed tomography (SPECT) can identify ischemic myocardium without evidence of
      myocardial infarction by the regional decline of tracer uptake. The present study
      compared BMIPP SPECT with rest-stress myocardial perfusion imaging (MPI) findings
      and coronary angiography (CAG) in 150 patients with acute chest pain. METHODS AND
      RESULTS: Patients with acute chest pain who underwent all of the following tests
      were selected: MPI at rest-stress, BMIPP SPECT at rest and CAG. Organic coronary
      artery stenosis (>or=75%) was observed in 46 patients, 27 patients had total or
      subtotal coronary occlusion by spasm in the spasm provocation test on CAG and the
      remaining 77 patients had no significant coronary artery stenosis or spasm. The
      sensitivity of BMIPP at rest to detect organic stenosis was significantly higher
      (54%) than that of rest-MPI (33%, p<0.005), but lower than that of stress-MPI
      (76%, p=0.05). The sensitivity of BMIPP at rest to detect spasm was significantly
      higher (63%) than that of both rest-MPI (15%; p<0.001) and stress-MPI (19%;
      p<0.001). Overall, the sensitivity of BMIPP at rest to detect both organic
      stenosis and spasm was significantly higher (58%) than that of rest-MPI (26%;
      p<0.001), despite having no significance with that of stress-MPI (55%). The
      specificity was not significantly different among the three imaging techniques.
      CONCLUSION: Resting BMIPP SPECT is an alternative method to stress MPI for
      identifying patients with not only organic stenosis but also spasm without the
      need for a stress examination.

PMID- 15170091
TI  - Endovascular stent - graft treatment for blunt aortic injury.
AB  - BACKGROUND: Thoracic aortic injury resulting from blunt trauma is usually fatal
      and almost always associated with multiple, complex, nonaortic injuries that can
      adversely affect standard surgical repair of the aorta. Endovascular stent -
      graft treatment offers these patients a less invasive operative treatment option.
      METHODS AND RESULTS: Between January 2002 and October 2003, 6 patients with blunt
      aortic injury (BAI) were treated with a stent - graft. In all cases endovascular
      management was selected because of associated polytrauma or comorbidities. All
      stent - grafts were homemade and deployed through the femoral artery with 18-20
      Fr delivery sheaths. There were no cases of perioperative death, renal failure,
      or neurologic complication. In one patient the postoperative computed tomography
      scan showed proximal endoleak requiring additional balloon dilatation and
      stenting. No other endoleaks were observed by CT in the acute phase. None of the
      follow-up CT scans revealed evidence of endoleak, migration, or alteration of the
      stent - graft. CONCLUSIONS: Endovascular repair for BAI is technically feasible
      and is an alternative to open surgery for high-risk patients.

PMID- 15170092
TI  - Prediction of clinical recurrence of atrioventricular-nodal reentrant tachycardia
      (AVNRT) after successful slow pathway ablation.
AB  - BACKGROUND: Even after successful slow pathway (SP) ablation for atrioventricular
      nodal reentrant tachycardia (AVNRT), there may be clinical recurrence in certain
      patients and it is clinically important to be able to predict that. METHODS AND
      RESULTS: In 97 patients with common type AVNRT, the effective refractory period
      (ERP) of the fast pathway (FP), SP-ERP, and prolongation of the atrio-His (AH)
      interval (AH) at the time of jump-up phenomenon were investigated. In patients
      with residual SP, parameters were re-evaluated in a similar manner. SP was
      successfully ablated and AVNRT was not inducible in all the patients, but
      residual SP was observed in 54 of the 97 patients, and there was late clinical
      recurrence in 10 patients (10/54 patients with residual SP and 0/43 without
      residual SP, p=0.002). The changes in FP-ERP before and after ablation (DeltaFP
      ERP) did not differ between recurrent and non-recurrent patients. Among the
      patients with residual SP, DeltaSP-ERP did not differ between the groups.
      However, the changes in DeltaAH before and after ablation (DeltaDeltaAH) were
      larger in non-recurrent (24+/-30 ms) than in the recurrent patients (4+/-7 ms,
      p=0.042). CONCLUSIONS: In patients with AVNRT, the residual SP and changes in
      DeltaAH after successful SP ablation might be useful indices of clinical
      recurrence.

PMID- 15170093
TI  - Long-term follow-up in japanese public office workers of the influence of blood
      pressure on ECG changes.
AB  - BACKGROUND: The relationship between annual changes in blood pressure (BP) and
      the electrocardiogram (ECG) was studied to clarity what factors give early
      detection of complications and predict the outcome of therapy. METHODS AND
      RESULTS: The influence of BP on the ECG was assessed in 830 Japanese office
      workers. Those with hypertension (HT) more frequently developed left atrial and
      ventricular overload compared with normotensive subjects. In addition, those with
      borderline HT (systolic pressure 140-160 mmHg and/or diastolic pressure 90-95
      mmHg) and even those with lower blood pressure (systolic pressure 130-140 mmHg
      and/or diastolic pressure 85-90 mmHg) developed left atrial and ventricular
      overload more frequently than normotensive subjects. CONCLUSIONS: Based on these
      results, BP should be closely followed up when routine systolic and diastolic
      pressure levels exceed 130 mmHg and 85 mmHg, respectively, in persons in their 40
      s to 50 s and the goal of antihypertensive therapy should be lower than reported
      previously.

PMID- 15170095
TI  - Comparisons of the skeletal muscle metabolic abnormalities in the arm and leg
      muscles of patients with chronic heart failure.
AB  - BACKGROUND: It has been suspected for some time that patients with chronic heart
      failure (CHF) have abnormal muscle metabolism, so in the present study the muscle
      metabolism of the arm and leg were compared by (31)P magnetic resonance
      spectroscopy ((31)P-MRS) to examine the relationship to exercise tolerance.
      METHODS AND RESULTS: The study group comprised 13 patients and 11 normal
      controls. Calf-plantar and forearm-wrist flexion were performed to evaluate the
      metabolic capacity assessed as the phosphocreatine breakdown rate (PCr-slope) and
      muscle pH at a submaximal (70% peak) work rate (submax-pH). Exercise of both the
      arm and leg resulted in an earlier decrease in PCr and muscle pH in patients with
      CHF compared with controls. There were significant correlations between peak
      oxygen uptake (peak V(O2)) and the PCr-slope in both limbs in patients with CHF
      (forearm: r=0.63, p<0.05; calf: r=0.60, p<0.05), but no correlations in normal
      controls. There was a close correlation between the ventilatory anaerobic
      threshold (AT) and the PCr-slope in the calf (r=0.85, p<0.01), but not in the
      forearm in patients with CHF. Submax-pH in both upper and lower limbs was not
      significantly correlated to peak V(O2) or AT in either patients with CHF or
      controls. CONCLUSIONS: Although metabolic abnormalities during exercise are seen
      in both arms and legs, leg muscle abnormalities, in particular, are closely
      related to systemic exercise intolerance in patients with CHF.

PMID- 15170094
TI  - Progressive nature of paroxysmal atrial fibrillation. Observations from a 14-year
      follow-up study.
AB  - BACKGROUND: Atrial fibrillation (AF) is believed to occur first as paroxysmal,
      then be gradually perpetuated, and finally become chronic as the end result.
      However, this presumed clinical course has not been well confirmed. METHODS AND
      RESULTS: The clinical course of recurrent paroxysmal AF (PAF) from its onset was
      examined in 171 patients (mean follow-up period: 14.1+/-8.1 years). This study
      population consisted of patients with no structural heart disease (n=88),
      ischemic heart disease (n=28), dilated or hypertrophic cardiomyopathy (n=17),
      valvular heart disease (n=35) or other cardiac diseases. The mean age at the
      onset of AF was 58.3 +/-11.8 years old. During the mean follow-up period of 14.1
      years, PAF eventually developed into its chronic form in 132 patients under
      conventional antiarrhythmic therapy (77.2%, 5.5% of patients per year). The
      independent factors for early development into chronic AF were aging (hazard
      ratio (HR) 1.27 per 10 years, 95% confidence interval (CI) 1.06-1.47)), dilated
      left atrium (HR 1.39 per 10 mm, 95% CI 1.11-1.69), myocardial infarction (HR
      2.33, 95% CI 1.13-4.81), and valvular diseases (HR 2.29, 95% CI 1.22-4.30).
      CONCLUSIONS: The present long-term observations definitely and quantitatively
      revealed the progressive nature of PAF.

PMID- 15170096
TI  - Effects of cellular cardiomyoplasty on ventricular remodeling assessed by Doppler
      echocardiography and topographic immunohistochemistry.
AB  - BACKGROUND: Myocardial infarction (MI) promotes deleterious remodeling of the
      myocardium, resulting in ventricular dilation and pump dysfunction. Supplementing
      infarcted myocardium with neonatal myocyte would attenuate deleterious remodeling
      and so the present study used Doppler echocardiography and histology to analyze
      the cardiac function and histological regeneration of the damaged myocardium
      after cellular cardiomyoplasty. METHODS AND RESULTS: Experimental MI was induced
      by 24-h coronary ligation followed by reperfusion in adult male Lewis rats and
      neonatal myocytes were injected directly into the infarct and peri-infarct
      regions. Three groups of animals were studied at 4 weeks after cellular
      cardiomyoplasty: noninfarcted control (control), MI plus sham injection (MI), and
      MI plus cell injection (MI + cell). Ventricular remodeling and cardiac
      performance were assessed by Doppler echocardiography or contrast
      echocardiography. At 4 weeks after cellular cardiomyoplasty, MI + cell hearts
      exhibited attenuation of global ventricular dilation and cardiac function
      compared with MI hearts not receiving cellular cardiomyoplasty.
      Immunohistochemically, connexin-43-positive small cells were observed in the
      vicinity of the infarction in MI + cell heart. By electron microscopy, these
      cells contained myofilaments with Z-bands and poorly developed intercalated
      disks, suggesting neonatal myocardial cells. Furthermore, the myocardial cells
      were often making close contact with interstitial cells. CONCLUSIONS: Implanted
      neonatal myocytes form viable grafts after MI, resulting in attenuated
      ventricular dilation and enhanced contractile function. Echocardiography,
      electron microscopy, and immunohistochemistry are useful methods for assessing
      the functional and histological regeneration of the damaged myocardium.

PMID- 15170098
TI  - Novel insertional mutation in the bone morphogenetic protein receptor type II
      associated with sporadic primary pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH), which results from occlusion of small
      pulmonary arteries, is a devastating condition. Mutations of the bone
      morphogenetic protein receptor type II gene (BMPR2), a component of the
      transforming growth factor- beta (TGF-beta) family, which plays a key role in
      cell growth, have recently been identified as causing familial and sporadic PPH.
      The first case of BMPR2 mutation found in Japan is reported here in a 19-year-old
      woman with a clinical diagnosis of PPH and no identifiable family history of
      pulmonary hypertension. Direct sequencing of the entire coding region and
      intron/exon boundaries of BMPR2 revealed a frameshift mutation predicted to alter
      the cell signaling response to specific ligands. A molecular classification of
      PPH, based upon the presence or absence of BMPR2 mutations, might have important
      implications for patient management and screening of relatives.

PMID- 15170097
TI  - Idiopathic long QT syndrome with early afterdepolarization induced by
      epinephrine. Acase report.
AB  - A patient with idiopathic long QT syndrome had repeated syncopal episodes. The
      QTc interval on the electrocardiogram at rest was 530 ms and was prolonged by
      exercise up to 740 ms with T wave alternation. Intravenous epinephrine (0.1
      microg/kg weight per min), but not isoproterenol (0.7 microg/min), produced early
      after depolarization of the monophasic action potential recorded at the right
      ventricular apex. Epinephrine prolonged the QTc interval to 710 ms. After the
      addition of propranolol to the epinephrine, the QTc (580 ms) was longer than at
      baseline. Methoxamine also prolonged the QTc to 580 ms. The QT interval in long
      QT syndrome is generally considered to be prolonged by a beta-adrenergic effect,
      but in the present case alpha-adrenergic stimulation had an additional effect on
      the prolongation of the QT interval.

PMID- 15170099
TI  - Assessment of myocardial perfusion and fatty acid metabolism in a patient with
      Churg-Strauss syndrome associated with eosinophilic heart disease.
AB  - Churg-Strauss syndrome is characterized by asthma, eosinophilia and systemic
      necrotizing vasculitis; cardiac involvement (ie, eosinophilic heart disease) is
      the major cause of morbidity and mortality, although there are no reports of an
      association between left ventricular dysfunction because of eosinophilic heart
      disease and myocardial blood flow or myocardial fatty acid metabolism. A patient
      presented with Churg-Strauss syndrome associated with eosinophilic heart disease
      that had progressed to dilated cardiomyopathy. Coronary angiography, thallium-201
      ((201)Tl) and iodine-123 beta-methyl-iodophenyl pentadecanoic acid ((123)I BMIPP)
      myocardial single photon emission computed tomography (SPECT) were performed to
      evaluate left ventricular dysfunction. Although coronary angiography was normal
      and (201)Tl SPECT showed no apparent image defect, (123)I BMIPP SPECT showed
      diffuse decreased accumulation, excepting the apex. The left ventricular
      dysfunction in patients with eosinophilic heart disease is associated with
      impaired myocardial fatty acid metabolism rather than with impaired myocardial
      blood flow.

PMID- 15170100
TI  - Pulmonary thromboembolism. Evaluating the indication and effect of a vena caval
      filter with indium-111-platelet scintigraphy.
AB  - A 63-year-old woman complained of chest pain and was referred to hospital where
      she was found to have left pleural effusion and swelling, local heat and edema of
      the right lower leg. Initial pulmonary perfusion scintigraphy demonstrated
      multiple defects and pulmonary thromboembolism (PTE) was confirmed during the
      anticoagulant and thrombolytic therapy against thrombophlebitis. A Greenfield
      filter was inserted in the inferior vena cava to prevent recurrence of PTE from
      the thrombosis that was resistant to therapy. In-111-labeled platelet
      scintigraphy (platelet scintigraphy) showed abnormal uptake of platelets in the
      chest, femoral veins and abdomen, which suggested active thrombus formation in
      those regions, including the filter, and a risk of recurrent PTE. Therefore, the
      thrombolytic therapy was terminated and the anticoagulant therapy intensified. A
      computed tomography (CT) scan revealed thrombus at the filter, which was markedly
      decreased 1 month later on platelet scintigraphy. Pulmonary ventilation and
      perfusion scintigraphy revealed remarkable improvement of the PTE. In this case,
      platelet scintigraphy complemented CT in demonstrating the activity and
      localization of the thrombus and can be used to evaluate the risk of recurrence
      during thrombolytic therapy after insertion of a filter.

PMID- 15170102
TI  - A new assay using surface plasmon resonance (SPR) to determine binding of the
      Lactobacillus acidophilus group to human colonic mucin.
AB  - A new binding assay to investigate the mechanism of adhesion of lactic acid
      bacteria to the human intestine was established by the surface plasmon resonance
      technique using a biosensor BIACORE1000. Cells of 26 strains of the Lactobacillus
      acidophilus group as analytes were eluted onto a sensor chip on which were
      immobilized biotinylated A-trisaccharide polymer probes having human A-type
      antigen [(GalNAcalpha1-3(Fucalpha1-2)Gal)-] or human colonic mucin of blood type
      A (HCM-A) as ligands. In the first screening, high adhesive affinity to the A
      trisaccharide BP-probe was observed in L. acidophilus OLL2769, L. crispatus
      JCM8778, LA205 and LA206. In the second screening, which used HCM-A, only L.
      acidophilus OLL2769 and L. crispatus JCM8778 were selected as adhesive strains
      with specific binding ability to human A-antigen. The results indicated that some
      strains of the L. acidophilus group could recognize and bind the sugar chain of A
      antigen structure on HCM.

PMID- 15170101
TI  - Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins:
      structures, pore-forming mechanism, and organization of the genes.
AB  - Staphylococcal gamma-hemolysin (Hlg), leukocidin (Luk), and Panton-Valentine
      leukocidin (PVL) are two-component and hetero-oligomeric pore-forming cytolytic
      toxins (or cytolysin), that were first identified in bacteria. No information on
      the existence of hetero-oligomeric pore-forming cytolytic toxins in bacteria
      except for staphylococcal strains is available so far. Hlg (Hlg1 of 34 kDa/Hlg2
      of 32 kDa) effectively lyses erythrocytes from human and other mammalian species.
      Luk (LukF of 34 kDa/LukS of 33 kDa) is cytolytic toward human and rabbit
      polymorphonuclear leukocytes and rabbit erythrocytes, and PVL (LukF-PV of 34
      kDa/LukS-PV of 33 kDa) reveals cytolytic activity with a high cell specificity to
      leukocytes. Hlg1 is identical to LukF and that the cell specificities of the
      cytolysins are determined by Hlg2 and LukS. Based on the primary and 3
      dimensional structures of the toxin components, Hlg, Luk, and PVL are thought to
      form a family of proteins. In the first chapter of this article, we describe the
      molecular basis of the membrane pore-forming nature of Hlg, Luk, and PVL. We also
      describe a requirement of the phosphorylation of LukS and LukS-PV by protein
      kinase for their leukocytolytic activity besides their pore formation on human
      leukocytes.Recently, the assembly mechanism of the LukF and Hlg2 monomers into
      pore-forming hetero-oligomers of Hlg on human erythrocyte membranes has been
      clarified for the first time by our study using a single-molecular fluorescence
      imaging technique. We estimated 11 sequential equilibrium constants for the
      assembly pathway which includes the beginning with membrane binding of monomers,
      proceeds through single pore oligomerization, and culminates in the formation of
      clusters of the pores. In the second chapter of this article, we refer to an
      assembly mechanism of LukF and Hlg2 on human erythrocytes as well as the roles of
      the membranes of the target cells in pore formation by Hlg. The LukF, LukS, and
      Hlg2 proteins are derived from the Hlg locus (hlg), and have been found in 99% of
      clinical isolates of Staphylococcus aureus. In contrast, LukF-PV and LukS-PV are
      derived from the PVL locus (pvl) which is distinct from the hlg locus, and only a
      small percentage of clinically isolated S. aureus strains carries pvl. Recently,
      we discovered pvl on the genome of lysogenic bacteriophages, psiPVL, and
      determined the entire gene of the phage. We also demonstrated the phage
      conversion of S. aureus leading to the production of PVL through the discovery of
      a PVL-carrying temperate phage, psiSLT, from a clinical isolate of S. aureus. In
      the third chapter of this article, we discuss genetic analyses of the Hlg, Luk,
      and PVL genes. We also discuss the current status of knowledge of the genetic
      organization of PVL-converting phages in order to achieve an understanding of
      their molecular evolution.

PMID- 15170103
TI  - Effect of difructose anhydride III on calcium absorption in humans.
AB  - The effects of difructose anhydride III (DFAIII) on stimulating calcium
      absorption was investigated in humans. We studied changes in the time-course of
      characteristics urinary calcium excretion in 12 healthy men given 0.3, 1.0 or 3.0
      g of DFAIII and 300 mg of calcium as calcium carbonate. In addition, urinary
      excretion and urine concentrations of creatinine and deoxypyridinoline were
      determined. Urine calcium excretion every 2 hours after the intake were higher
      over than that of the control subjects. The total amount of urinary calcium
      excretion for 10 hours was significantly greates in the subjects given 1.0 g or
      3.0 g of DFAIII than that of the control subjects. However, there were no
      differences in the urine concentrations of creatinine and deoxypyridinoline
      between the subjects given DFAIII and the control subjects. These findings
      suggests that low dose of DFAIII had a stimulating effect on calcium absorption
      in humans.

PMID- 15170104
TI  - Elevation of intracellular cAMP levels by dominant active heterotrimeric G
      protein alpha subunits ScGP-A and ScGP-C in homobasidiomycete, Schizophyllum
      commune.
AB  - In many fungi, the heterotrimeric G protein alpha subunits, and/or small G
      protein (RAS) control intracellular cAMP levels. But it is not clear which types
      of G proteins modulate cAMP levels in homobasidiomycete (mushrooms). To explain
      the mechanism, we expressed dominant active RAS (a homolog of S. cerevisiae RAS1)
      in homobasidiomycete Schizophyllum commune and compared the cAMP levels in the
      transformed clones with those of clones expressing dominant active heterotrimeric
      G protein alpha subunits ScGP-A, B, and C. The results demonstrated that the
      dominant active ScGP-A and C elevated the intracellular cAMP levels. In contrast,
      the dominant active S. commune RAS gene did not affect the cAMP levels, even
      though colony growth and formation of fruiting bodies were apparently repressed.
      These data suggest that the heterotrimeric G protein alpha subunits are involved
      in the mechanism of cAMP regulation, and that RAS modulates another signal
      transduction pathway regulating cell growth and differentiation.

PMID- 15170105
TI  - Anti-microbial action against verotoxigenic Escherichia coli O157:H7 of nitric
      oxide derived from sodium nitrite.
AB  - The levels of verotoxin-1 and verotoxin-2 released by verotoxigenic Escherichia
      coli O157:H7 treated in vitro with sodium nitrite, sodium chloride and several
      antibiotics were evaluated. Of the three strains of E. coli O157:H7 used in this
      study, two strains produced both verotoxin-1 and verotoxin-2, and one strain
      produced only verotoxin-2. Treatment of E. coli O157:H7 with sodium nitrite (6000
      mg/l, minimum inhibitory concentration) did not increase the levels of verotoxin
      1 and verotoxin-2 compared with a treatment by sodium chloride or antibiotics.
      When the electron paramagnetic resonance spectrum of sodium nitrite-treated
      bacterial cells was examined at 77 K to clarify the mechanism for the anti
      bacterial activity of nitric oxide derived from sodium nitrite, electron
      paramagnetic resonance signals with g-values of 2.035 and 2.010 were observed.
      These were identified as being derived from iron-nitric oxide complexes. It
      appears that the dinitrosyl iron complexes in the E. coli O157:H7 cells were
      generated from the reaction of iron-sulfur proteins (enzymes) with nitric oxide
      formed by the reduction of sodium nitrite. The amount of ATP was decreased by the
      presence of sodium nitrite in the cell suspension. These findings indicate that
      nitric oxide derived from sodium nitrite penetrated the cells and inactivated
      enzymes related to the respiratory chain.

PMID- 15170106
TI  - Effect of a taurine treatment on the regression of existing atherosclerotic
      lesions in rabbits fed on a high-cholesterol diet.
AB  - We studied whether taurine has any regressive effect on existing atherosclerotic
      lesions and lipid peroxidation in rabbits fed on a high-cholesterol (HC) diet.
      The cholesterol, triglyceride, malondialdehyde (MDA) and diene conjugate (DC)
      levels, as well as the aortic histopathological findings were examined in rabbits
      that had been fed on a cholesterol-containing diet for 8 months [0.5% cholesterol
      (w/w) for 3 months and subsequently 0.25% cholesterol (w/w) for 5 months], and
      then for a further 4 months on a normal diet with or without taurine treatment
      [1% (w/v) in the drinking water]. High levels of lipid and lipid peroxide induced
      by the HC diet were observed to decline in the plasma, liver and aorta of
      atherosclerotic rabbits, as well as a slight retardation in aortic
      atherosclerotic lesions during the regression period. Although no significant
      differences in the lipid and lipid peroxide levels in the plasma and aorta were
      found between the regressed groups with or without the taurine treatment, the
      extent of atherosclerotic lesions in the aorta was less in the taurine-treated
      regressed group than in the non-treated regressed group. However, the liver MDA
      and DC levels were lower in the regressed rabbits with the taurine treatment in
      the non-treated group. These results indicate that the taurine treatment may
      accelerate the regression of cholesterol-induced atherosclerotic lesions in
      rabbits without having any effect on the plasma and aorta lipid and lipid
      peroxide levels.

PMID- 15170107
TI  - Evaluation of the preventive effect of isoflavone extract on bone loss in
      ovariectomized rats.
AB  - To examine a potential role for soybean phytoestrogens in postmenopausal bone
      loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4
      groups and given controlled diets for 16 weeks. The treatment groups were as
      followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract
      (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). OVX treatments reduced femoral
      and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased
      uterine weight (p<0.01), accelerated body weight increases (p<0.05), and
      increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and
      tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone
      prevented the losses of bone density and mineral content caused by OVX (p<0.01).
      Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing
      ability on the OVX-induced bone loss, the effect of isoflavone was not the same
      as that of 17beta-estradiol on the serum ALP and TRAP, body weight increase, and
      uterine weight change. We concluded that dietary supplementation with soybean
      isoflavone can prevent postmenopausal bone loss via a different mechanism of
      estrogen in OVX rats.

PMID- 15170108
TI  - Improving the pyrophosphate-inosine phosphotransferase activity of Escherichia
      blattae acid phosphatase by sequential site-directed mutagenesis.
AB  - Escherichia blattae acid phosphatase/phosphotransferase (EB-AP/PTase) exhibits C
      5'-position selective pyrophosphate-nucleoside phosphotransferase activity in
      addition to its intrinsic phosphatase. Improvement of its phosphotransferase
      activity was investigated by sequential site-directed mutagenesis. By comparing
      the primary structures of higher 5'-inosinic acid (5'-IMP) productivity and lower
      5'-IMP productivity acid phosphatase/phosphotransferase, candidate residues of
      substitution were selected. Then a total of 11 amino acid substitutions were made
      with sequential substitutions. As the number of substituted amino acid residues
      increased, the 5'-IMP productivity of the mutant enzyme increased, and the
      activity of the 11 mutant phosphotransferases of EB-AP/PTase reached the same
      level as that of Morganella morganii AP/PTase. This result shows that Leu63,
      Ala65, Glu66, Asn69, Ser71, Asp116, Thr135, and Glu136, whose relevance was not
      directly established by structural analysis alone, also plays an important role
      in the phosphotransferase activity of EB-AP/PTase.

PMID- 15170109
TI  - Isoflavones found in Korean soybean paste as 3-hydroxy-3-methylglutaryl Coenzyme
      A reductase inhibitors.
AB  - 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase is the rate-limiting enzyme in
      the biosynthesis of cholesterol in mammals. Some microbial metabolites have been
      found to be HMG-CoA reductase inhibitors. Korean soybean paste is a unique food
      fermented by many microorganisms. The enzymatic method using the catalytic domain
      of Syrian hamster HMG-CoA reductase was employed for the screening of HMG-CoA
      reductase inhibitors. Soybean paste extract was fractionated by vacuum liquid
      chromatography. Fractions showing relatively high HMG-CoA reductase inhibition
      were further purified through Sephadex LH-20 column chromatography and C18
      preparative HPLC, and the inhibitory compounds were identified as genistein,
      daidzein, and glycitein.

PMID- 15170110
TI  - Characterization of endo-beta-N-acetylglucosaminidase from alkaliphilic Bacillus
      halodurans C-125.
AB  - The genome sequencing project on alkaliphilic Bacillus halodurans C-125 revealed
      a putative endo-beta-N-acetylglucosaminidase (Endo-BH), which consists of a
      signal peptide of 24 amino acids, a catalytic region of 634 amino acids
      exhibiting 50.1% identity with the endo-beta-N-acetylglucosaminidase from
      Arthrobacter protophormiae (Endo-A), and a C-terminal tail of 220 amino acids.
      Transformed Escherichia coli cells carrying the Endo-BH gene exhibited endo-beta
      N-acetylglucosaminidase activity. Recombinant Endo-BH hydrolyzed high-mannose
      type oligosaccharides and hybrid type oligosaccharides, and showed
      transglycosylation activity. On deletion of 219 C-terminal amino acid residues of
      Endo-BH, the wild type level of activity was retained, whereas with deletions of
      the Endo-A homolog domain, the proteins were expressed as inclusion bodies and
      these activities were reduced. These results suggest that the enzymatic
      properties of Endo-BH are similar to those of Endo-A, and that the C-terminal
      tail does not affect the enzyme activity. Although the C-terminal tail region is
      not essential for enzyme activity, the sequence is also conserved among endo-beta
      N-acetylglucosaminidases of various origins.

PMID- 15170111
TI  - Dietary branched-chain amino acids suppress the expression of pancreatic amylase
      mRNA in rats.
AB  - Regulators for pancreatic amylase were examined. Rats were fed ad libitum a 20%
      amino acid (AA) mixture diet (Con), a 60% AA diet (HA), a branched-chain amino
      acid (BCAA)-rich diet (BC), or a diet supplemented with AA other than BCAA (OA)
      for 7 d, or fed the Con, HA, BC diets or diets supplemented with individual BCAA.
      Activity and mRNA levels of pancreatic amylase in the BC and HA groups were lower
      than those in the Con and OA groups. Leucine and isoleucine contributed to these
      effects of the BC diet. The mRNA levels correlated with individual pancreatic
      BCAA concentrations but not with plasma insulin level. In conclusion, dietary
      BCAA, especially leucine and isoleucine, may reduce amylase mRNA and activity in
      rats.

PMID- 15170112
TI  - Enzymatic properties and nucleotide and amino acid sequences of a thermostable
      beta-agarase from the novel marine isolate, JAMB-A94.
AB  - A gene, agaA, for a novel beta-agarase from the marine bacterium JAMB-A94 was
      cloned and sequenced. The 16S rDNA of the isolate had the closest match, of only
      94.8% homology, with that from Microbulbifer salipaludis JCM11542(T). The agaA
      gene encoded a protein with a calculated molecular mass of 48,203 Da. The deduced
      amino acid sequence showed 37-66% identity to those of known agarases in
      glycoside hydrolase family 16. A carbohydrate-binding module-like amino acid
      sequence was found in the C-terminal region. The recombinant enzyme was hyper
      produced extracellularly when Bacillus subtilis was used as a host. The purified
      enzyme was an endo-type beta-agarase, yielding neoagarotetraose as the main final
      product. It was very thermostable up to 60 degrees C. The optimal pH and
      temperature for activity were around 7.0 and 55 degrees C respectively. The
      activity was not inhibited by EDTA (up to 100 mM) and sodium dodecyl sulfate (up
      to 30 mM).

PMID- 15170113
TI  - Purification, cloning, and sequence analysis of beta-N-acetylglucosaminidase from
      the chitinolytic bacterium Aeromonas hydrophila strain SUWA-9.
AB  - A chitinolytic bacterium was isolated from Lake Suwa and identified as Aeromonas
      hydrophila strain SUWA-9. The strain grew well on a synthetic medium containing
      colloidal chitin as sole carbon source. Chitin-degrading activity was induced by
      colloidal chitin or N-acetylglucosamine (GlcNAc). Most of the activity, however,
      was not detected in culture fluid but was associated with cells. A beta-N
      acetylglucosaminidase was purified after it was solubilized from cells by
      sonication. The purified enzyme hydrolyzed N-acetylchitooligomers from dimer to
      pentamer and produced GlcNAc as a final product. The enzyme also hydrolyzed
      synthetic substrates such as p-nitrophenyl (pNP)-N-acetyl-beta-D-glucosaminide
      and pNP-N-acetyl-beta-D-galactosaminide. A gene coding for the purified beta-N
      acetylglucosaminidase was isolated. The ORF identified is 2661 nucleotides long
      and encodes a precursor protein of 887 amino acids including a signal peptide of
      22 amino acid residues. The amino acid sequence deduced showed a high similarity
      to those of bacterial beta-N-acetylhexosaminidases classified in family 20 of
      glycosyl hydrolases.

PMID- 15170114
TI  - Gelling properties of soybean beta-conglycinin having different subunit
      compositions.
AB  - The effects of protein concentration, and heating temperature and time on the
      gelling properties of soybean beta-conglycinin (7S globulins) lacking the alpha
      or alpha' subunit were compared with those of 7S containing all three subunits
      (alpha, alpha', and beta) to determine whether each subunit contributes equally.
      In most of the conditions, the relative order of gel hardness was alpha'-lacking
      > 7S > alpha-lacking. From Fourier transform infrared studies, the secondary
      structure change after heating was very similar among the three samples; thus,
      the secondary structural change is not the reason for the differences in gel
      hardness. By using scanning electron microscopy, we observed differences in
      strand thickness and the density of the gel network among the three samples.
      These differences correlated well with the differences in gel hardness.

PMID- 15170115
TI  - Synthesis of brassinosteroids of varying acyl side chains and evaluation of their
      brassinolide-like activity.
AB  - Brassinosteroids containing various side chain moieties were synthesized and
      their activity was determined as the reciprocal logarithm of the ED(50) (50%
      effective dose per plant in moles) in the rice lamina inclination assay using
      synergist indole-3-acetic acid (IAA). The introduction of a hydroxyl group in the
      alpha-position to the carbonyl group of the ester structure significantly
      enhanced the activity. 2alpha,3alpha-Dihydroxy-17beta-[(2R,3S)-2-hydroxy-3
      methylpentanoyl]oxy-B-homo-7-oxa-5alpha-androstan-6-one showed the highest
      activity, for which the pED(50) was determined to be 10.5 under synergistic
      conditions with IAA. Under identical conditions, the pED(50) values of
      brassinolide and castasterone were determined to be 13.6 and 12.3 respectively.
      With respect to the alpha-carbon of the acyl moiety, the R-form was 10 times more
      potent than the corresponding S-form. Substituting the terminal structure (Et) of
      the side chain to that of the most potent compound, brassinolide (i-Pr), did not
      increase the activity.

PMID- 15170116
TI  - Isolation of flavohemoglobin from the actinomycete Streptomyces antibioticus
      grown without external nitric oxide stress.
AB  - A flavocytochrome protein was isolated from the actinomycete Streptomyces
      antibioticus. The purified protein contained protoheme and FAD, and its M(r) was
      estimated to be 52000. The absorption spectra in its resting oxidized, dithionite
      reduced, carbon monoxide-bound, and oxygenated (O(2)-bound) forms were
      characteristic of those of flavohemoglobin (Fhb). The N-terminal amino acid
      sequence showed high identities to those of other Fhb's. Furthermore, the
      actinomycete flavocytochrome scavenged nitric oxide in the presence of NADH.
      These results demonstrated that the flavocytochrome is the first Fhb purified
      from actinomycetes. The actinomycete Fhb was produced in S. antibioticus cells in
      large amounts without any external nitric oxide (NO) stress, which is indicative
      of a physiological function of Fhb other than detoxification of NO.

PMID- 15170117
TI  - Effects of truncation at the non-homologous region of a family 3 beta-glucosidase
      from Agrobacterium tumefaciens.
AB  - The function of the non-homologous region of a family 3 beta-glucosidase from
      Agrobacterium tumefaciens (Cbg1) was studied by analyzing the properties of
      mutant enzymes that have internal truncated amino acid sequences in the region.
      Five truncated mutants named Cbg1-d4, Cbg1-d31, Cbg1-d62, Cbg1-d89, and Cbg1-d119
      having deletions of 4, 31, 62, 89, and 119 amino acid residues starting from
      Phe417, respectively, were expressed in Escherichia coli and purified. All the
      mutants exhibited beta-glucosidase activity, indicating that the non-homologous
      region was not essential for the activity. The truncation caused thermal
      instability, decrease in pK(a) of the proton donor residue (Glu616), and
      deficient transglycosylation activity. The thermal stability and the pK(a) of
      Glu616 were partially recovered with longer truncation, suggesting that the
      truncation perturbed the structure and that their presence in the region was not
      essential. The main role of the non-homologous region could be formation of a
      hydrophobic atmosphere at the acceptor site to make the enzyme suitable for
      hydrolyzing hydrophobic glucosides.

PMID- 15170118
TI  - Identification of high molecular weight proteins in squid muscle by Western
      blotting analysis and postmortem rheological changes.
AB  - The high molecular weight protein connectin (also called titin) in Japanese
      common squid (Todarodes pacificus) mantle muscle was identified by western
      blotting analysis with 3B9, the mouse anti-chicken skeletal muscle connectin
      monoclonal antibody. Similarly to vertebrate samples, there exists connectin in
      invertebrate squid mantle muscle, and the amino acid sequences are assumed to
      resemble those present in the A band of vertebrate connectin, judging by the
      specificity of 3B9. Moreover, the connectin in squid muscle migrated in this
      study as a closely spaced doublet of alpha and beta (titins 1 and 2). Between 5
      and 7 h post-mortem, the SDS PAGE patterns of the squid sample indicated a change
      of the doublet bands into a single beta-connectin band. Simultaneously, the
      rheological properties of the squid muscle changed substantially. This
      degradation of alpha-connectin into beta-connectin in the muscle can explain the
      critical change that occurs during the post-mortem tenderization of squid muscle.

PMID- 15170120
TI  - New monoterpene glucoside from the aerial parts of thyme (Thymus vulgaris L.).
AB  - A new monoterpene glucoside (1) was isolated from a methanol extract of the dried
      aerial parts of thyme (Thymus vulgaris L.), together with known 2- and 5-beta-D
      glucopyranosylthymoquinols (2 and 3, respectively), and (-)-angelicoidenol-beta-D
      glucopyranoside (4). The structure of 1 was elucidated to be (R)-p-cymen-9-yl
      beta-D-glucopyranoside by spectral evidence and enantioselective synthesis from
      (R)- and (S)-p-cymen-9-ol derived from p-cymen-8-ol.

PMID- 15170119
TI  - Novel Fusicoccins R and S, and the fusicoccin S aglycon (phomopsiol) from
      Phomopsis amygdali niigata 2-A, and their seed germination-stimulating activity
      in the presence of abscisic acid.
AB  - Our search for new 3-hydroxyfusicoccins structurally related to cotylenin A from
      a culture of Phomopsis amygdali Niigata 2-A resulted in the isolation of novel 3
      hydroxy fusicoccins, called fusicoccins R and S, and the fusicoccin S aglycon,
      called phomopsiol, together with known 3alpha-hydroxyfusicoccin J. The structure
      of phomopsiol was identified as that of O-demethyl-3-epicotylenol based on
      spectroscopic evidence. The structures of fusicoccins R and S were also
      determined to be those of 3'-deacetyl-3alpha-hydroxyfusicoccin A and 3beta
      hydroxy-3-epifusicoccin H. The lettuce seed germination-stimulating activity of
      fusicoccins R and S, phomopsiol and 3alpha-hydroxyfusicoccin J was examined in
      the presence of ABA; fusicoccin R and 3alpha-hydroxyfusicoccin J were highly
      active, while fusicoccin S and phomopsiol were inactive. The possible
      biosynthetic relationships among these novel fusicoccins having a 3alpha- or
      3beta-hydroxy group in their diterpene moiety are briefly discussed.

PMID- 15170121
TI  - Suppressive effects of dietary fiber in yogurt on the postprandial serum lipid
      levels in healthy adult male volunteers.
AB  - This study assessed the effect of partially hydrolyzed guar gum (PHGG) in yogurt
      on the elevation of postprandial serum lipid levels. Eleven healthy adult male
      subjects were given yogurt with or without 6 g of PHGG in a fat tolerance test as
      a crossover study. Supplementation with 6 g of PHGG significantly suppressed the
      incremental peaks and areas under the incremental curve (AUIC) of postprandial
      serum remnant-like lipoprotein particle cholesterol (RLP-C) and triglyceride
      (TG). The results suggest the potential of PHGG to reduce the risk of
      hyperlipemia.

PMID- 15170123
TI  - Enzymatic reactions by five chalcone synthase homologs from hop (Humulus lupulus
      L.).
AB  - The enzyme activities encoded in five cDNAs for chalcone synthase (CHS) homologs
      from hop were investigated. Only valerophenone synthase (VPS) and CHS_H1 showed
      both naringenin-chalcone and phlorisovalerophenone forming activity. Narigenin
      chalcone production by VPS was much lower than by CHS_H1. Therefore, it is highly
      possible that flavonoid depends mainly on CHS_H1, while bitter acid biosynthesis
      depends mainly on VPS and CHS_H1.

PMID- 15170122
TI  - Design of soymetide-4 derivatives to potentiate the anti-alopecia effect.
AB  - Previously, we found that soymetide-4 (MITL), an N-formyl-methionyl-leucyl
      phenylalanine (fMLP) agonist peptide derived from soybean beta-conglycinin alpha'
      subunit, stimulated phagocytosis of human polymorphonuclear leukocytes, and
      inhibited alopecia induced by etoposide, an anticancer drug, in neonatal rats
      after oral administration. We found that the fMLP receptor affinity and
      phagocytosis-stimulating activity of soymetide-4 was potentiated by replacement
      of Thr(3) with hydrophobic residues. Among the derivatives synthesized, [Trp](3)
      soymetide-4 (MIWL) was the most potent, stronger by 180 and 130 times than
      soymetide-4 in receptor affinity and phagocytosis-stimulating activity,
      respectively. The anti-alopecia effect of [Trp](3)-soymetide-4 was about 3 times
      larger than that of soymetide-4 after oral administration.

PMID- 15170125
TI  - Catalytic activity of tripeptidase from Lactococcus lactis to which amino acid
      substitution was introduced according to natural mutation.
AB  - Four mutations observed between tripeptidases from Lactococcus lactis subsp.
      lactis and subsp. cremoris were introduced one by one to the corresponding points
      in wild-type tripeptidase from L. lactis subsp. lactis. The k(cat) values of four
      resultant mutants were analyzed and discussed in stereographical terms. Change in
      catalytic activity appeared to be related to the sequential and steric location
      of mutation point within the enzyme protein, even though no drastic change was
      observed with one point mutation.

PMID- 15170124
TI  - Isolation of an exopolysaccharide-producing bacterium, Sphingomonas sp. CS101,
      which forms an unusual type of sphingan.
AB  - An exopolysaccharide-producing Gram negative bacterium was isolated and
      determined to be a Sphingomonas sp. (CS101). A sugar composition analysis of an
      exopolysaccharide indicated that the Sphingomonas sp. CS101 secreted an
      exopolysaccharide composed of glucose, mannose, fucose, and rhamnose in the ratio
      of 2.1:1.1:1.0:0.1, suggesting that this exoplysaccharide is an unusual type of
      sphingan family. The mean molecular weight of the exopolysaccharide was
      determined to be 4.2x10(5) Da by size exclusion chromatography coupled with multi
      angle laser-light scattering (SEC/MALLS) analysis. An exopolysaccharide was
      produced up to 17 g/l (pH 7; 30 degrees C) with the optimal medium condition over
      4 days of cultivation.

PMID- 15170127
TI  - Involvement of a Glu71-Arg64 couple in the access channel for NADH in cytochrome
      p450nor.
AB  - Putative access channel for NADH in the heme-distal pocket of cytochrome p450nor
      (p450nor) comprises many charged amino acid residues. Characterization of the
      E71A mutant protein of p450nor highlights the existence of a unique mechanism for
      binding NADH that depends on the salt bridge network between Glu71, Arg64 and
      Asp88.

PMID- 15170126
TI  - Effects of soybean beta-conglycinin on hepatic lipid metabolism and fecal lipid
      excretion in normal adult rats.
AB  - beta-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar
      adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the
      beta-conglycinin-fed group significantly increased as against the casein-fed
      group. Hepatic fatty acid synthase activity in the beta-conglycinin group
      significantly decreased as against that of the casein-fed group. Fecal fatty acid
      excretion in the beta-conglycinin group was significantly higher than in the
      casein group.

PMID- 15170128
TI  - Resistance imparted by traditional Chinese medicines to the acute change of
      glutamic pyruvic transaminase, alkaline phosphatase and creatine kinase
      activities in rat blood caused by noise.
AB  - The activities of serum glutamic pyruvic transaminase (GPT), alkaline phosphatase
      (ALP) and creatine kinase (CK) in rats injected or not with the Chinese
      medicines, Astragali, Rhodiolae and Ligusticum, were determined after noise
      exposure. Noise at 95 and 105 dB significantly increased the activities of GPT,
      ALP and CK, and showed a dependence on the exposure time. The injection of each
      medicine significantly suppressed the increased enzyme activities by 95 and 105
      dB noise.

PMID- 15170129
TI  - Biotransformation of alpha-isomethylionone to 1-(2,6,6-trimethyl-2-cyclohexen-1
      yl)propan-2-one.
AB  - The main biodegradation product of (+/-)-alpha-isomethylionone (2) with standard
      activated sludge was characterized as (+/-)-1-(2,6,6-trimethyl-2-cyclohexen-1
      yl)propan-2-one (1) by its analysis and synthesis. Both enantiomers (1a and 1b)
      of 1 were synthesized by starting from (R)- and (S)-2,4,4-trimethyl-2-cyclohexen
      1-ol (3a and 3b), respectively.

PMID- 15170130
TI  - Microbial hydroxylation of indole to 7-hydroxyindole by Acinetobacter
      calcoaceticus strain 4-1-5.
AB  - A screening study yielded Acinetobacter calcoaceticus strain 4-1-5, which is
      capable of hydroxylating indole to 7-hydroxyindole. Strain 4-1-5 grew on
      terephthalate as the sole source of carbon and energy and hydroxylated indole to
      7-hydroxyindole by cometabolism of indole using terephthalate as cosubstrate.
      Strain 4-1-5 produced 0.574 mM of 7-hydroxyindole at 2.38 mM indole in 24 h with
      the cell growth.

PMID- 15170131
TI  - Characterization of protein phosphatase 2A acting on phosphorylated plasma
      membrane aquaporin of tulip petals.
AB  - A protein phosphatase holo-type enzyme (38, 65, and 75 kDa) preparation and a
      free catalytic subunit (38 kDa) purified from tulip petals were characterized as
      protein phosphatase 2A (PP2A) by immunological and biochemical approaches. The
      plasma membrane containing the putative plasma membrane aquaporin (PM-AQP) was
      prepared from tulip petals, phosphorylated in vitro, and used as the substrate
      for both of the purified PP2A preparations. Although both preparations
      dephosphorylated the phosphorylated PM-AQP at 20 degrees C, only the holo-type
      enzyme preparation acted at 5 degrees C on the phosphorylated PM-AQP with higher
      substrate specificity, suggesting that regulatory subunits are required for low
      temperature-dependent dephosphorylation of PM-AQP in tulip petals.

PMID- 15170136
TI  - High expression of integrin beta1 and p53 is a greater poor prognostic factor
      than clinical stage in small-cell lung cancer.
AB  - The purpose of this study was to investigate the possible association between
      expression of integrin beta1 and p53 and survival in patients with small-cell
      lung cancer (SCLC). One hundred four patients with SCLC who had received an
      initial course of a full-dose of combination chemotherapy between February 1989
      and July 1999 were entered in the study. Transbronchial biopsy specimens of
      tumors obtained before chemotherapy were subjected to immunostaining for integrin
      beta1 and p53. Twenty-eight and 58 patients could not be evaluated for integrin
      beta1 and p53 immunostaining, respectively, because the tissue samples had been
      crushed during the biopsy. Fifty-four patients had tumors with less than or equal
      to 25% integrin beta1-positive cells and 22 patients had tumors with more than
      25% integrin beta1-positive cells, whereas 19 and 27 patients had tumors with
      less than or equal to 50% and more than 50% p53-positive cells, respectively. By
      comparison, the overall survival of patients with high expression of integrin
      beta1 and p53 were significantly worse than those of individuals whose tumors had
      low expression (log-rank test, p = 0.046 and p = 0.0067, respectively). Moreover,
      the overall survival of patients with high expression of either integrin beta1 or
      p53 (n = 42) was significantly worse than that of other patients without high
      expression of integrin beta1 and p53 (n = 38; log-rank test, p = 0.0003; Wilcoxon
      test, p = 0.0026). The association between survival and prognostic factors,
      including gender, age, performance status, clinical stage, and integrin beta1/p53
      expression was examined by the Cox proportional hazards model; only integrin
      beta1/p53 expression was found to be a significant independent factor (hazard
      ratio = 0.394, p = 0.0005). In conclusion, the high expression of integrin beta1
      and p53 in tumor cells is a greater poor prognostic factor than clinical stage in
      patients with SCLC.

PMID- 15170137
TI  - Multiple primary cancers in patients with osteosarcoma: influence of anticancer
      drugs and genetic factors.
AB  - One hundred thirty-five patients younger than 30 years with osteosarcoma were
      treated at the Chiba Cancer Center between 1976 and 1999. They included six
      patients with second cancer after cure of osteosarcoma (group A) and three
      patients with osteosarcoma as second cancer after cure of childhood cancers
      (group B). Third cancer occurred in one patient of group A. The clinical features
      of these nine patients were studied. The diagnoses of second cancer in group A
      consisted of two acute myelogenous leukemias, two breast carcinomas, one
      malignant phyllodes tumor of breast, and one ovarian carcinoma. The third cancer
      was uterine leiomyosarcoma. Second cancer occurred an average of 7.2 years after
      occurrence of osteosarcoma. The diagnoses of first cancer in group B consisted of
      one adrenocortical carcinoma, one malignant teratoma of sacrum, and one ovarian
      carcinoma (yolk sac tumor). Osteosarcoma occurred on average 12.7 years after
      occurrence of first cancer. Two patients had germ-line p53 gene mutation.
      Anticancer drugs and genetic factors are presumed to be concerned with occurrence
      of second cancer. The frequency of multiple primary cancers in patients with
      osteosarcoma is by no means low. Strict follow-up is thus needed over a long
      period.

PMID- 15170138
TI  - Clinical value of protein S100 and melanoma-inhibitory activity (MIA) in
      malignant melanoma.
AB  - Serum protein S100 and melanoma-inhibitory protein (MIA) have been described as
      useful tumor markers for malignant melanoma. In this study, these two serum
      proteins were compared in 48 patients with melanoma at different stages of
      disease. Serum concentrations of S100 and MIA were measured by immunoradiometric
      and enzyme-linked immunosorbent assays, respectively. We found that the cut-off
      values were 17.4 ng/ml for MIA and 0.09 microg/l for S100. Five patients had
      stage I-II, 22 had stage III, and 21 had stage IV disease. Serum levels of two
      markers were elevated with metastatic disease (p < 0.05). Sensitivities of the
      MIA were found higher compared with S100 in patients with extensive (M1c)
      metastatic disease and with chemotherapy nonresponders (p > 0.05). We showed a
      trend for worsened outcome in patients with elevated MIA level in univariate
      analysis. MIA was found to be more sensitive and is a potential prognostic marker
      for patients with metastatic malignant melanoma in comparison with S100.

PMID- 15170139
TI  - Phase II study of ifosfamide plus daily oral etoposide in previously treated
      ovarian cancer: a Hoosier Oncology Group (HOG) study.
AB  - Advanced epithelial ovarian carcinoma is a chemosensitive tumor to platinum plus
      paclitaxel combination chemotherapy. However, most patients develop recurrences
      following their initial platinum-based regimen and are candidates for subsequent
      chemotherapy. Several chemotherapeutic drugs have been tested as single
      therapeutic agents or in combination for relapsed epithelial ovarian carcinoma.
      The response rate has been modest with no obvious advantage to combination
      chemotherapy versus single agents. Both oral etoposide and ifosfamide have shown
      activity as single agents in pretreated patients. We completed a phase II study
      at the Hoosier Oncology Group utilizing oral etoposide plus ifosfamide in
      patients with relapsed ovarian epithelial carcinoma. Fourteen patients entered
      the study. Ifosfamide was given intravenously (IV) at a dose of 1.2 g/m2/d on
      days 1 to 4 with mesna 300 mg/m2 IV 15 minutes prior to and 4 and 8 hours after
      ifosfamide infusion. Etoposide was administered as 37.5 mg/m2/d orally on days 1
      to 14. This regimen was repeated every 28 days until disease progression or for a
      maximum of 6 cycles. Grade III to IV granulocytopenia occurred in 9 patients
      (64%), with 2 neutropenic infections, but with no therapy-related deaths. Grade
      III to IV thrombocytopenia occurred in 3 patients (21%), and grade III to IV
      nausea and vomiting in 1 patient. No renal, pulmonary, hepatic, cardiac, or
      serious neurotoxicity was observed. Two patients (14%) achieved partial response,
      and additional 5 (35%) patients had stable disease. The 1-year survival
      probability using Kaplan-Meier analysis was 0.8. In this small sample-size trial,
      we did not demonstrate an advantage to this combination regimen compared to these
      or other single agents.

PMID- 15170140
TI  - Topotecan in patients with advanced neuroendocrine tumors: a phase II study with
      significant hematologic toxicity.
AB  - New agents with antitumor activity in neuroendocrine tumors are sorely needed. We
      therefore conducted a phase II study of topotecan (TOPA) 1.5 mg/m2/d for 5 days
      every 3 weeks in 22 patients with advanced carcinoid and islet cell tumors.
      Severe neutropenia in 8 of 11 patients (72%) prompted a 30% dose reduction of
      TOPA to 1.05 mg/m2 for the final 11 patients enrolled. No objective responses
      were observed. Eighteen patients have progressed and 14 have died. The median
      time to progression was 4.2 months (95% CI: 2.9-6.5) and the median survival was
      1.9 years (95% CI: 0.63-2.3). Hematologic adverse events were significant, with
      16 of 22 patients developing grade IV neutropenia; however, there were no septic
      deaths. Nonhematologic adverse events were infrequent and were not dose limiting.
      In conclusion, further studies of this schedule of TOPA in this patient
      population are not recommended due to the lack of tumor response and significant
      hematologic toxicity.

PMID- 15170141
TI  - Treatment of thymoma: a comparative study between Thailand and the United States
      and a review of the literature.
AB  - This article provides a unique perspective on thymoma by describing the clinical
      scenarios from 2 diverse patient populations followed by an update. A comparative
      chart review was conducted on patients diagnosed at 2 university-based hospitals,
      1 in the United States and 1 in Thailand. A comprehensive review of the
      literature was then performed through MEDLINE for articles between 1980 and 2002.
      During the last 23 years, charts from 16 patients at each institution were
      available for review. The most common presenting symptoms were myasthenia gravis
      (47%), dyspnea (25%), and chest discomfort (19%) and are similar to those
      reported in the literature. The primary treatment of stages I-III disease
      included surgery with or without radiation. Trimodality therapy with surgery,
      radiotherapy, and chemotherapy was pursued in 43% of patients with stage IV
      disease in the United States, whereas no patients from Thailand underwent this
      regimen. Median overall survivals were 124 and 76 months in the Thai and the US
      groups, respectively (P = 0.76). No major differences in the clinical features
      were observed between the 2 institutions, although a trend toward more advanced
      disease was seen in the United States. Surgery and radiation remain the backbone
      of treatment, but the role for chemotherapy is increasing.

PMID- 15170142
TI  - Primary pancreatic plasmacytoma.
AB  - We report an extremely rare case of primary pancreatic plasmacytoma. A 56-year
      old man had a 4-cm mass in the pancreatic tail and received distal
      pancreatectomy. This mass mainly consisted of plasma cells, but we failed to
      demonstrate their monoclonality in spite of the immunohistological staining. One
      and a half years later, this patient's right inguinal node swelled, and this node
      also showed a dense plasma cell infiltration. A very precise immunohistological
      staining was performed for this lymph node and the previous pancreatic mass, and
      both were diffusely positive for kappa light chain, IgG, and CD38. In the absence
      of myeloma elsewhere, we thus reached the correct diagnosis of primary pancreatic
      plasmacytoma, which later metastasized to lymph nodes. In the presence of the
      plasma cell proliferation in a pancreatic mass, plasmacytoma should be taken into
      consideration, and a more careful immunohistological staining is definitely
      necessary.

PMID- 15170143
TI  - High-dose chemotherapy and autologous stem cell transplant in women with de novo
      chemosensitive metastatic breast cancer.
AB  - The prognosis of patients with de novo stage IV breast cancer seems to be similar
      to that of patients with metastatic disease. Because these patients have not been
      exposed to prior therapy, the use of high dose chemotherapy (HDCT) may be
      beneficial. Twenty-four newly diagnosed (median age 42) responding metastatic
      breast cancer patients underwent HDCT (Stamp V) and stem cell support as their
      initial treatment. The predominant sites of metastatic disease were bone (12),
      lung (5), liver (2), lymph nodes (6), marrow (4), and soft-tissue (1).
      Estrogen/progesterone receptors were positive in 35%, negative in 45%, and
      unknown in 20%. Before transplantation, 10 patients were in complete remission
      (CR), 6 were in partial remission (PR), and 8 were inevaluable. Radiotherapy was
      administered to sites of documented metastatic disease. Tamoxifen was given to
      patients with receptor positive and unknown tumor status. After a median follow
      up of 60 months from diagnosis (range 42 to 96 months), 15 patients have relapsed
      and 10 died. Mean and median progression free survival from transplant are 53 (SE
      6.6, CI 40-66) and 60 (SE 18, CI 25-96) months, respectively. The median survival
      has not yet been achieved (>6 years). There was no treatment-related mortality.
      The use of HDCT in patients with chemosensitive, de novo metastatic breast cancer
      is safe and well tolerated. Overall clinical outcome is good; however, this study
      cannot determine whether this was due to treatment or selection bias.

PMID- 15170145
TI  - Is there a "curative" role of radiotherapy for clinically localized hormone
      refractory prostate cancer?
AB  - Whether definitive radiotherapy (RT) is still an option for patients with
      clinically prostate-confined prostate cancer treated with androgen deprivation
      (AD) alone who develop a rising prostate-specific antigen (PSA) is not clear. In
      this retrospective series, we report the outcome of 29 such patients treated with
      "curative" radiotherapy at our institution between 1991 and 2000. At initial
      diagnosis, all patients had evidence of prostate-confined disease and for several
      reasons underwent AD alone. Afterward all patients developed rising PSA, but
      again, without clinical evidence of distant/pelvic node disease. All underwent RT
      with curative intent up to 70 Gy (66 to 76 Gy). Median follow-up after
      radiotherapy is 33.1 month (range: 7-134.2 months). For living patients, minimum
      and median follow-ups are 30.4 and 55.4 months, respectively. Twenty-three
      patients (79%) developed overt clinical disease, most of which (19/23, 83%)
      involved distant sites, whereas isolated locoregional failure was observed in
      only 4 patients (4/23, 17%). The estimates of locoregional control rate (LRC),
      actuarial incidence of distant metastases, and overall survival at 5 years are 89
      +/- 7%, 68 +/- 9%, and 28 +/- 9%, respectively. Although we were unable to find
      any predictor of LRC at univariate analysis, patients with low Gleason score at
      diagnosis, lower PSA at RT, lower risk category and advanced age were less likely
      to develop distant disease. RT has a palliative role, because most patients with
      still presumed localized hormone refractory prostate cancer will develop distant
      metastases. A subset of patients, those with more differentiated tumor at
      diagnosis and with pre-RT PSA less than 20 ng/mL, might be considered for a more
      aggressive locoregional approach.

PMID- 15170146
TI  - Dose and dose intensity effect of adjuvant anthracycline-based chemotherapy in
      early breast cancer: a retrospective analysis.
AB  - The purpose of this study was to determine the importance of the dose of adjuvant
      chemotherapy in patients with breast cancer, and to determine which variables had
      influence on the dose of chemotherapy received. We reviewed the records of 196
      patients with node-positive breast carcinoma that were treated with anthracycline
      based adjuvant chemotherapy. We analyzed the influence on treatment efficacy of
      the dose of anthracyclines (total dose and dose intensity), and a multivariate
      analysis was performed to identify independent prognostic factors of chemotherapy
      total dose. There were no differences in disease-free survival or overall
      survival between patients who received doses below or above the median total dose
      and median dose intensity of anthracyclines. A positive correlation was observed
      between the total dose of anthracycline received and the number of axillary lymph
      nodes. The clinical outcome of patients with node-positive breast cancer
      receiving adjuvant anthracycline-based chemotherapy is not affected by the amount
      of chemotherapy delivered. There exists a clinical practice of administering more
      chemotherapy in patients with poorer prognosis, which does not result in better
      therapeutic outcomes.

PMID- 15170144
TI  - Radiation therapy with or without chemotherapy for cervical cancer with
      periaortic lymph node metastasis.
AB  - The purpose of this article is to evaluate the efficacy of chemoradiation therapy
      (CRT) and radiation therapy (RT) alone for cervical cancer with periaortic nodal
      metastasis (PANM). Twenty-one patients with cervical cancer with PANM were
      identified. Eleven patients received concomitant CRT with cisplatin-based
      chemotherapy and 10 received RT alone. The median age was 44 years. Ten, 5, and 6
      patients had International Federation of Gynecology and Obstetrics stages IB,
      IIB, and IIIB disease. The RT doses to point A and the periaortic region were 80
      to 85 Gy (low dose rate equivalent) and 45 Gy. The median follow-up was 26 months
      (range 3 to 141 months). The 1- and 3-year disease-specific survival were 81.8%
      and 81.8%, and 70% and 30%, respectively, for the CRT and RT groups, (P = 0.11).
      The 1- and 3-year pelvic and periaortic control rates (PPC) were 100% and 100%
      (CRT), and 56.3% and 42.2% (RT) (P = 0.03). The 1- and 3-year free-from-distant
      metastasis (DM) rates were 81.8% and 81.8% (CRT), and 78.7% and 49.2% (RT) (P =
      0.54). All patients who developed DM died of their disease. CRT is a feasible
      treatment option to improve the PPC for these patients. Because of the high rate
      of distant metastasis despite PPC, more effective systemic therapy should be
      explored.

PMID- 15170147
TI  - Internal mammary lymph node (IMN) coverage by standard radiation tangent fields
      in patients showing IMN drainage on lymphoscintigraphy: therapeutic implications.
AB  - The purpose of this report is to evaluate the variability in coverage of the
      internal mammary nodal chain (IMN) by standard radiation tangential fields in
      those patients with medial drainage on lymphoscintigraphy. Twenty-two patients
      who showed lymphoscintigraphic IMN drainage underwent radiation simulation
      planned with computed tomography (CT). Standard tangent fields were placed and CT
      scans were reviewed to assess IMN inclusion and correlation with presternal fat
      thickness. Of the 22 patients who showed IMN drainage on lymphoscintigraphy, 10
      (45%) had lateral primary lesions, 9 (41%) had medial lesions and 3 (14%) had
      subareolar lesions. Of these 22 women, 4 (19%) had the IMN completely within the
      standard tangent fields. Twelve women (55%) had only partial coverage of the IMN
      and the remaining 6 women (27%) had the IMN region completely outside. Presternal
      fat thickness greater than 10 mm was less likely associated with complete IMN
      coverage than fat thickness 10 mm or less, P = 0.001. Lymphoscintigram drainage
      to the IMN in breast cancer patients may suggest an increased risk of IMN
      involvement. Our data show that a majority (73%) of these patients had complete
      or partial incidental inclusion of the IMNs with standard tangents, which may in
      part explain the historically low IMN failure rate.

PMID- 15170148
TI  - The HD12 panel of the German Hodgkin Lymphoma Study Group (GHSG): a quality
      assurance program based on a multidisciplinary panel reviewing all patients'
      imaging.
AB  - The purpose of this report is to determine the value of a central specialist
      radiologic review and to determine the image quality of computed tomography (CT)
      in Hodgkin disease. The HD12 protocol is a multicenter prospective randomized
      trial of the GHSG for advanced stages of Hodgkin disease. The indication and
      effectiveness of additional radiotherapy (30 Gy), in the area of initial bulky
      disease and of residual disease, following intensive chemotherapy using the
      BEACOPP schema (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine,
      procarbazine, prednisone), is to be investigated. A multidisciplinary panel of
      radiation oncologists, radiologists, and medical oncologists reviews, blinded to
      treatment arms, the diagnostic imaging with comparison to the documentation
      forms. For patients with poor response to chemotherapy, the panel recommends
      radiotherapy independent of the randomization. This procedure guarantees that
      patients with a poor response to chemotherapy receive additional radiotherapy.
      Furthermore, the panel evaluates the quality of CT examinations in this
      multicenter study. Since July 1999, a total of 2607 CT of 371 patients have been
      evaluated. Helical CT showed significantly higher contrast enhancement and
      imaging quality than conventional CT (P < 0.001). CT from university hospitals
      was assessed as superior to that from other institutions (P < 0.001). Compared
      with the written disease documentation by the study centers, the panel assessed
      different extensions of disease in 814 of 2607 CT (31%), resulting in a change of
      stage in 17 of 371 patients (5%). After chemotherapy, 167 of 371 patients (45%)
      showed residual disease (>1.5 cm), and for 53 of 371 patients (14%) the panel
      recommended additional radiotherapy independent of the randomization arm.
      Patients with Hodgkin disease receive high-quality CT imaging. A central
      independent multidisciplinary panel markedly improves quality assurance for these
      study patients.

PMID- 15170149
TI  - The value of postexcision preradiation mammography in patients with early-stage
      breast cancer.
AB  - The purpose of this study was to evaluate the benefit of postexcision
      preradiation mammography for patients with early-stage breast cancer. The records
      of 101 patients (103 breasts) with either ductal carcinoma in situ (DCIS) or
      early invasive breast cancer diagnosed based on microcalcifications on a
      mammogram between January 1999 and December 2001 at our institution were
      reviewed. Sixty-one patients had a postexcision preradiation mammogram, and 42
      patients did not have a mammogram until the completion of radiation. Of the 61
      patients who had a preradiation mammogram, 1 patient (2%) was found to have
      residual microcalcifications after the completion of chemotherapy. A core biopsy
      revealed DCIS, and a wide excision revealed no additional abnormalities. Of the
      42 patients who underwent a postradiation mammogram, 1 patient had calcifications
      in the same quadrant as her original biopsy. A wide excision revealed only
      sclerosing adenosis. For women who receive chemotherapy before the initiation of
      radiation, a preradiation mammogram ought to be considered because there will
      frequently be a 6-month interval from the patient's lumpectomy to the initiation
      of radiation. However, for women scheduled to start radiation within an interval
      of 4 months or less, our data do not support the routine use of postexcision
      preradiation mammography. Although we recognize that our data may not be
      representative of the community at large, our observations do not support the
      routine use of postexcision preradiation mammography in women with small breast
      cancers.

PMID- 15170150
TI  - Gemcitabine in patients with solid tumors and renal impairment: a pharmacokinetic
      phase I study.
AB  - The purpose of this phase I study was to determine the pharmacokinetics and
      toxicity of gemcitabine in patients with advanced, recurrent, and/or metastatic
      cancer and renal impairment. Patients were entered in 4 groups estimated by EDTA
      Cr plasma clearance (CLp, mL/min): > or =80; > or =60 and <80; > or =30 and <60;
      and > or =30 and <80 plus renal insufficiency induced by previous chemotherapy,
      respectively. Gemcitabine 500 to 1000 mg/m was administered intravenously on days
      1, 8, and 15 every 4 weeks. Plasma concentration data were pooled and analyzed
      using a population pharmacokinetic program (NONMEM). Eighteen white patients (14
      females, 4 males) entered the study with a median age of 55 years. Linear
      regression analyses revealed no significant relationship between gemcitabine CLp
      and indices of renal impairment (EDTA-Cr CL; p = 0.797 or beta2-microglobulin; p
      = 0.153). Hematologic and nonhematologic toxicities were mild. Thus, there seems
      to be no significant impact of mild to moderate renal insufficiency on
      gemcitabine pharmacokinetics in patients with advanced cancer.

PMID- 15170151
TI  - Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis
      in advanced colorectal cancer patients.
AB  - This phase I-II trial was designed to assess the effect of irinotecan on
      oxaliplatin pharmacokinetics and to determine the MDT of both drugs when
      administered in combination. Treatment was repeated every 2 weeks.
      Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best
      sequence and detect any interaction between the two drugs. Thirty-four patients
      with advanced colorectal cancer were enrolled; 28 of them (82%) had liver
      involvement. The main toxicities were neutropenia and delayed diarrhea; 5
      patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was
      experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients,
      respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No
      pharmacokinetic interactions between irinotecan and oxaliplatin were detected.
      The recommended dose for future phase II trials is oxaliplatin 85 mg/m and
      irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de
      Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent
      secondary hepatectomy with curative intent, and two of them are long-term disease
      free survivors. It would appear that the dose and schedule defined by this trial
      could be proposed as front-line therapy for advanced colorectal carcinoma to
      establish rapid disease control and to permit patients to proceed to surgery.

PMID- 15170152
TI  - Paclitaxel, cisplatin, and vinorelbine combination chemotherapy in metastatic non
      small-cell lung cancer.
AB  - Vinorelbine-cisplatin combination chemotherapy is a standard approach for the
      treatment of advanced non-small-cell lung cancer (NSCLC). The addition of
      paclitaxel as a third therapeutic agent seems promising. The aim of the present
      study was to evaluate the activity and toxicity of this new regimen. Forty-six
      nonselected and chemotherapy-naive patients with stage IV NSCLC and an Eastern
      Cooperative Oncology Group performance status of 0 to 2 were treated every 4
      weeks with paclitaxel (135 mg/m2 given iv in 3 hours) and cisplatin (120 mg/m2
      given iv in 6 hours) on day 1 and vinorelbine (30 mg/m2 given iv in 30 minutes)
      on days 1 and 15. All patients were evaluated for toxicity and response according
      to the intent-to-treat principle. An objective response was observed in 39% of
      the patients (95% CI: 25% to 55%). World Health Organization grade III to IV
      neutropenia, thrombocytopenia, and anemia occurred in 43%, 2%, and 17%,
      respectively. There was one treatment-related death. Nonhematologic toxicities
      were mild, mainly grade III nausea and vomiting in 20% of the patients. After a
      median follow-up period of 54 months, the median progression-free survival was
      14.3 weeks and the median overall survival was 31.3 weeks. This three-drug
      chemotherapy combination is feasible, well tolerated, and shows activity in
      metastatic NSCLC.

PMID- 15170153
TI  - Ratio between positive lymph nodes and total dissected axillaries lymph nodes as
      an independent prognostic factor for disease-free survival in patients with
      breast cancer.
AB  - The number of positive axillary lymph nodes involved by tumor is one of the main
      prognostic factors for women with locoregional breast cancer (BC) for whom
      adjuvant chemotherapy is being considered. The prognostic importance of the ratio
      (P/D) between positive lymph nodes (P) and total dissected lymph nodes (D),
      previously demonstrated in the high-dose chemotherapy (HDC) setting has not yet
      been tested, however, in the conventional adjuvant chemotherapy setting. The data
      of 168 patients who were from 2 institutions and who were treated with adjuvant
      chemotherapy for BC were retrospectively analyzed, and univariate and
      multivariate analysis were performed, including the other traditional prognostic
      factors and P/D ratio as possible predictors of disease free survival (DFS).
      Disease-free survival for quartile 4 of P/D ratio (ratio >0.30) was statistically
      different from that for the other quartiles (log-rank test p < 0.001). Mean DFS
      for this series was not reached as well as for quartiles 1, 2, and 3, while mean
      DFS for quartile 4 was 44.5 months. In univariate analysis, number of positive
      lymph nodes (r2 = 0.055; p = 0.023), P/D ratio (r2 = 0.213; p < 0.001), and stage
      (r2 = 0.105; p = 0.002) were predictive of relapse, while in multivariate
      analysis, only P/D ratio remained an independent predictor of relapse (r2 =
      0.213; p < 0.001). It is concluded that P/D ratio could become a simple,
      inexpensive, and easily available prognostic factor for patients undergoing
      conventional chemotherapy for BC.

PMID- 15170154
TI  - Adriamycin and cis-platinum as first-line treatment in unresectable locally
      advanced or metastatic adult soft-tissue sarcomas.
AB  - Standard chemotherapy in advanced adult soft-tissue sarcomas (STS) has not yet
      been established. We evaluated the efficacy and toxicity of the combination of
      adriamycin (ADR) and cis-platinum (CDDP) as first-line treatment in nonoperable
      locally advanced or metastatic adult STS. Thirty patients were treated with CDDP
      100 mg/m2 on day 1 and ADR 75 mg/m2 equally divided on days 1 to 3, every 3 weeks
      for 6 cycles. Patients were evaluated for response, toxicity, and survival, while
      resectability of residual disease was also assessed after the third cycle and the
      end of chemotherapy. No complete response was observed. Five patients (16.7%, 95%
      CI: 2.5%-31%) achieved partial response, 16 patients (53.3%, 95% CI: 34%-72%) had
      stable disease and 9 patients (30%, 95% CI: 13%-47%) had progressive disease. The
      overall median survival was 11.5 months (range, 4-96 months), and the median time
      to disease progression was 6 months (range, 0-96 months). Furthermore, two
      patients with PR and six patients with stable disease underwent further surgery
      followed by radiotherapy in four of them. At present, 5 patients remain free of
      relapse for 96, 90, 72, 60, and 48 months, respectively. Treatment-related
      toxicity was acceptable, with moderate myelosuppression and alopecia as the main
      adverse events. The ADR/CDDP regimen was well tolerated, but it did not achieve a
      high response rate. However, patients with resectable disease after chemotherapy
      achieved long-term survival. Further studies are needed to evaluate the role of
      combined-modality treatments in the management of patients with advanced STS.

PMID- 15170155
TI  - Primary mediastinal large B-cell lymphoma: clinical study of a distinct clinical
      entity and treatment outcome in 20 patients: review of the literature.
AB  - Primary mediastinal B-cell lymphoma (PMBCL) is a discrete subset of large B-cell
      lymphoma with unique clinicopathologic features. The question of optimal
      treatment emerges because it is an uncommon but not rare occurrence. A
      retrospective study was therefore conducted in a group of patients in Greece to
      evaluate the clinical features and treatment outcome in this disease. Twenty
      patients with PMBCL, with a median age of 42 years, treated at centers
      participating in the Hellenic Cooperative Oncology Group over the last 20 years,
      were reviewed. Thirteen (65%) had bulky disease at the time of presentation, 7
      (35%) had superior vena cavae obstruction, and 15 (75%) had extranodal
      involvement. All received doxorubicin-containing chemotherapy, followed in 11
      cases by mediastinal radiotherapy. With a median follow-up of 91 months, the
      median survival is 67.7 months. These data are consistent with those reported
      from other centers concerning the patient's characteristics, natural history,
      response pattern to chemoradiation therapy, and prognosis. Response to therapy
      proved of prognostic significance. A key question that remains is the prompt
      identification of patients who would benefit from innovative or more intensive
      therapies.

PMID- 15170156
TI  - Phase II study of paclitaxel combined with vinorelbine in patients with advanced
      breast cancer.
AB  - Paclitaxel and vinorelbine are two drugs active against breast cancer. A phase II
      study was initiated with the aim of assessing the efficacy and feasibility of the
      combination. Twenty-six patients presenting with advanced breast cancer with a
      taxane- and vinorelbine-free line of chemotherapy were included and treated with
      vinorelbine (20 mg/m2 on D1, D15), followed by paclitaxel (175 mg/m2 on D1),
      every 3 weeks. A 48% (95% CI: 35-61) response rate was obtained in the 23
      patients evaluable for response. Vinorelbine was administered on D15, as
      scheduled, in 72% of cycles. The main toxicity observed was grade III to IV
      neutropenia in 73% of patients. Febrile neutropenia was reported in three
      patients. Disease-free survival was 118 days, and overall median survival was 361
      days. This combination of paclitaxel and vinorelbine is feasible and effective in
      patients with early relapse or previously treated with first-line chemotherapy
      for metastatic disease.

PMID- 15170157
TI  - Long-term remission of myelofibrosis following nonmyeloablative allogeneic
      peripheral blood progenitor cell transplantation in older age: the Scripps Clinic
      experience.

PMID- 15170158
TI  - Erythrocyte antigen and reticulocyte engraftment after allogeneic hematopoietic
      stem cell transplantation.
AB  - The aim of this study was to study the usefulness of erythrocyte antigen (EA)
      measurement to study engraftment after allogeneic HSCT. In all, 31 consecutive
      patients receiving HLA-identical bone marrow (BM) (n=13) or peripheral blood stem
      cells (n=18) were investigated. Apart from the ABO group, 15 EAs representing six
      minor blood groups were followed by the simple tube agglutination technique. A
      total of 20 (64.5%) patients received ABO-identical, eight (25.8%) received ABO
      minor and three (9.7%) received ABO major mismatched grafts. In all, 29 patients
      were followed for a median of 12 (6-16) months; 65% of the patients expressed
      donor type EA 1 month and almost all did so 6 months after transplant.
      Reticulocyte engraftment was significantly shorter than EA engraftment (median 18
      vs 35 days) (P=0.001). Patients who received PB stem cells showed significantly
      faster EA and reticulocyte engraftment than patients who received BM stem cells
      (P=0.038 and 0.025). ABO compatibility did not have an impact on reticulocyte and
      EA engraftment (P=0.4 and 0.55). The earliest donor type EA detected was from the
      Rh and Kidd system. These data suggest that EA and reticulocyte assays are useful
      in monitoring engraftment.

PMID- 15170159
TI  - Autoimmune thrombocytopenia following tandem autologous peripheral blood stem
      cell transplantation for refractory germ cell tumor.

PMID- 15170160
TI  - Successful use of Campath-1H in the treatment of steroid refractory liver GvHD.

PMID- 15170161
TI  - Nonmyeloablative stem cell transplantation with a haploidentical donor in a class
      3 lucarelli severe thalassemia patient.

PMID- 15170162
TI  - Defibrotide for hepatic VOD in children: exact statistics can help!

PMID- 15170163
TI  - Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in
      recipients of allogeneic stem cells from blood or bone marrow.
AB  - A total of 61 patients with haematological malignancies were randomised either to
      allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM), of
      whom 37 patients gave their consent to participate in a skin biopsy trial. Skin
      biopsies were performed before and after transplantation. The main objective was
      to assess whether biopsies of normal and affected skin from patients allografted
      with BSC showed a different histopathological and immunohistochemical pattern as
      compared to biopsies taken from patients allografted with BM. In addition, we
      wished to clarify whether sequential skin biopsies could be of prognostic value
      with regard to graft-versus-host disease (GVHD). Biopsies from normal or affected
      skin in BSC allografted did not disclose a different pattern as compared to BM
      transplants. Biopsies taken before the outbreak of acute and chronic GVHD showed
      no substantial differences between the groups. Irrespective of the type of
      allograft, the immunohistochemical picture of affected skin consistent with acute
      GVHD was dominated by a significantly higher number of T-lymphocytes (CD8+).
      Biopsies from normal skin before the outbreak of GVHD had no predictive value
      with regard to the development of acute or chronic GVHD. Immunohistochemistry is
      of supplementary help in distinguishing changes caused by cytotoxic agents from
      those caused by acute GVHD.

PMID- 15170164
TI  - Successful non-T-cell-depleted nonmyeloablative hematopoietic stem cell
      transplantation (NST) from an HLA-haploidentical 2-loci-mismatched sibling in a
      heavily transfused patient with severe aplastic anemia based on the fetomaternal
      microchimerism.
AB  - A 37-year-old Japanese man with systemic hemochromatosis due to multiple
      transfusions was referred to us for the treatment of severe aplastic anemia
      (SAA), from which he had been suffering for 24 years. The patient had diabetes
      arising from the hemochromatosis, chronic anal fissures, and a kidney abscess due
      to neutropenia. He was treated with a nonmyeloablative preconditioning regimen
      followed by non-T-cell-depleted (non-TCD) allogeneic peripheral blood stem cell
      transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical 2
      loci-mismatched sibling. Prompt engraftment of granulocytes and platelets was
      observed, and graft-versus-host disease was easy to control. Noninherited
      maternal antigens in the donor were confirmed prior to PBSCT, and they were also
      detected in small quantities in the recipient. This report describes the first
      successful nonmyeloablative hematopoietic stem cell transplant in a heavily
      transfused SAA patient from an HLA-haploidentical 2-loci-mismatched sibling
      donor. The result suggests that a long-term fetomaternal microchimerism-positive
      sibling can be a second-line donor if an alternative HLA-identical donor is not
      available.

PMID- 15170165
TI  - Citrulline: a potentially simple quantitative marker of intestinal epithelial
      damage following myeloablative therapy.
AB  - We noted a significant decline in the serum concentrations of citrulline of 32
      haematopoietic stem cell transplant recipients following intensive myeloablative
      therapy during the first 3 weeks after transplantation when patients have oral
      mucositis, a markedly disturbed gut integrity (L/R ratio) and are most at risk of
      infection and other severe complications. Closer inspection of the citrulline
      concentrations of 12 patients confirmed that the decline did indeed correspond to
      the onset of oral mucositis and altered gut integrity. Since serum citrulline is
      a reliable biochemical marker of small bowel enterocyte mass in humans with
      villous-atrophy-associated diseases, it may prove a useful marker for intestinal
      mucosal damage induced by chemotherapy, allowing the relationship between gut
      mucosal damage and post-transplant complications including infections to be
      explored more readily.

PMID- 15170166
TI  - Clinical outcomes with intensive therapy for patients with primary resistant
      multiple myeloma.
AB  - Clinical outcomes were evaluated in 89 consecutive patients with multiple myeloma
      that had not responded to dexamethasone-based primary therapy, who received early
      intensive therapy supported by autologous stem cell transplantation. Results were
      compared with those of 45 comparable patients who refused or were unable to
      receive intensive treatment for socioeconomic reasons. Following high-dose
      therapy, the response rate was 69% including 16% with CR. Survival of 14 patients
      with CR (median >7.0 years) was significantly longer than those of 47 patients
      with PR (median 4.5 years) or of 28 patients who remained NR (median 2.2 years).
      CR occurred in 43% of patients with serum myeloma protein <1.5 gm/dl, in contrast
      to 7% of those with higher values, a finding similar to that observed previously
      for patients consolidated in PR. No prognostic factor was associated with PR and,
      in view of the high frequencies of PR or CR, all patients with primary resistant
      myeloma should be considered for early intensive therapy. The limited improvement
      of lifespan and disease-free survival for those in PR indicated the need for
      further treatment to achieve CR, the major surrogate marker for long survival.

PMID- 15170167
TI  - A prospective study of health-related quality of life, fatigue, anxiety and
      depression 3-5 years after stem cell transplantation.
AB  - Health-related quality of life (HRQOL), fatigue and psychological distress were
      prospectively assessed in 248 cancer patients treated with allogeneic (SCT,
      N=61), or autologous (ASCT, N=69) stem cell transplantation or conventional
      chemotherapy (CT, N=118) of whom 128 completed the assessments after 3 years. The
      European Organization for Treatment and Research of Cancer Core Quality of Life
      Questionnaire and the Hospital Anxiety and Depression Scale were administered
      nine (SCT/ASCT groups) or seven times (CT group) during the first year. The
      Fatigue Questionnaire was added at the final assessment. The SCT group displayed
      greater changes from baseline scores than the ASCT group, with more symptoms in
      the first months post transplant. A gradual improvement was found in both groups
      during the following 4-6 months, before stabilizing at baseline levels. Only
      minor changes were observed after the first year. All groups reported more
      fatigue than the population values after 3 years (P<0.01). The ASCT group also
      reported less optimal HRQOL (P<0.01-0.0001). No differences were found in anxiety
      and depression. Despite a faster recovery during the first months after
      transplant, the ASCT patients reported poorer functioning and more fatigue
      compared to the SCT group after 3 years. This suggests a need for a closer follow
      up of these patients with special emphasis on functional status and fatigue.

PMID- 15170168
TI  - Increased cell turnover, but no signs of increased T-cell infiltration or
      inflammatory cytokines in the duodenum of pediatric patients after allogeneic
      stem cell transplantation.
AB  - Intestinal immunopathology was studied after allogeneic stem cell transplantation
      (SCT) in a common clinical setup in 20 children with malignant (n=17) or
      nonmalignant diseases (n=3) receiving grafts from siblings (7) and unrelated
      donors (13). In all, 19 had total body irradiation. Duodenal biopsies at 6 and 12
      weeks post transplant were evaluated by histology, immunohistochemistry, and ISEL
      for the detection of T-lymphocytes, inflammatory cytokines, proliferation, and
      apoptosis. The controls were 12 healthy children and three patients with proven
      intestinal graft-versus-host disease. An increased rate of apoptosis and
      proliferation with upregulated expression of HLA-DR antigen was detected up to 3
      months post transplant in the SCT patients, even in those with a histologically
      normal small intestine. A low level of IFNgamma and TNFalpha was observed in the
      lamina propria. The initial low density of gammadelta-positive T cells had
      recovered to normal by the time of the second endoscopy at 12 weeks post
      transplant. We conclude that inflammatory activity and T cell infiltration
      detected by immunohistochemistry may not belong to the 'normal' recovery of the
      small intestine after SCT. Increased cell turnover in the intestinal crypts
      continues until 3 months after SCT, suggesting either an unexpectedly long
      lasting effect of transplant-related toxicity or, preferably, an ongoing
      subclinical alloreactive process, also present in the patients without intestinal
      symptoms.

PMID- 15170169
TI  - Autologous stem cell transplantation using modified TAM or combination of triple
      alkylating agents conditioning regimens as one of the post-remission treatments
      in patients with adult acute myeloid leukemia in first complete remission.
AB  - A total of 174 newly diagnosed adult acute myeloid leukaemia (AML) patients were
      treated in first complete remission (CR1) using modified TAM or a combination of
      triple-alkylating agents followed by autologous transplantation (AT). Cytogenetic
      risk groups were classified and most patients received mobilized peripheral blood
      stem/progenitor cells (PBSCs). The infused cell dose consisted of a median of
      4.1+/-2 (range, 1.2-17.1)x 10(6)/kg CD34+ cells. With a median follow-up of 51
      months (range, 5-131 months) after CR1, the estimated 5-year disease-free
      survival (DFS) rate was 68 (95% confidence interval (CI), 63-73%) and the event
      free survival rate at 5 years was 59 (95% CI, 54-64%). AML patients other than M3
      subtype, the long-term DFS rate was 76, 33% for favourable and unfavourable risk
      groups, respectively. In all, 40 patients had relapses (40/174, 23%) at the
      median 15 months after CR1 (range, 8-66 months). Overall, seven patients (4%)
      died in connection with AT. The infused CD34+ cell dose (P=0.0389) was associated
      with survival by multivariate analysis. In conclusion, two novel conditioning
      regimens in AT are feasible for adults with variable risk AML followed for over a
      10-year period.

PMID- 15170170
TI  - Prognostic value of bone marrow angiogenesis in patients with multiple myeloma
      undergoing high-dose therapy.
AB  - Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an
      important prognostic factor. However, prior studies were mainly done on patients
      receiving conventional chemotherapy and there is limited data on its prognostic
      value in patients undergoing high-dose therapy (HDT) as initial therapy. We
      studied BM angiogenesis in terms of microvessel density (MVD) in 88 newly
      diagnosed patients, who were uniformly treated, with 3-4 cycles of induction
      chemotherapy followed by HDT. We examined if MVD at diagnosis was predictive of
      response to induction therapy or to subsequent HDT. In addition, we also examined
      its prognostic value in these patients. The median MVD for primary refractory
      patients was 28 (range, 2-84) compared to 27 (range, 2-99) for responding
      patients (P=0.7). The median progression-free survival (PFS) was 21 months for
      those with high-grade angiogenesis compared to 42 months for those with low-grade
      angiogenesis, P=0.017. The median overall-survival (OS) from diagnosis was 40
      months for those with high-grade angiogenesis and not yet reached, for those with
      low-grade angiogenesis, P=0.007. BM MVD at the time of initial diagnosis is an
      important prognostic factor for OS and PFS in patients undergoing autologous
      transplantation as frontline therapy for myeloma.

PMID- 15170171
TI  - A model of in vivo purging with Rituximab and high-dose AraC in follicular and
      mantle cell lymphoma.
AB  - We studied a model of in vivo purging with Rituximab and high-dose (HD)
      cytarabine in 14 patients with relapsed/refractory follicular lymphoma and two
      with refractory mantle cell lymphoma enrolled in a program of HD chemotherapy and
      autotransplant. After two courses of debulking immunochemotherapy with Rituximab,
      Vincristine and Cyclophosphamide, we used a combination of Rituximab, HD
      cytarabine and granulocyte colony-stimulating factor for peripheral blood stem
      cells (PBSC) mobilization. The median number of CD34+ cells collected was 14.69 x
      10(6)/kg (range 5.74-73.2). Monitoring of peripheral CD19+ and CD20+ B cells
      prior to and throughout the purging period showed that a treatment with
      Rituximab, Vincristine and Cyclophosphamide results in a profound depletion of B
      cells in peripheral blood. B-cell depletion persists during mobilization with
      Rituximab and HD cytarabine allowing a collection of PBSC free of B cells (median
      CD19+ and CD20+ cells counts 0%). Of nine patients PCR positive for bcl-2 or bcl
      1 in blood and marrow at the start of immunochemotherapy, all showed PCR-negative
      PBSC. In conclusion, in patients with indolent lymphoma, the concurrent
      administration of Rituximab and HD cytarabine is a safe and efficient method to
      obtain in vivo purged PBSC. Immunochemotherapy prior to mobilization produces B
      cell depletion and seems to be a useful preparative step.

PMID- 15170172
TI  - Effects of allogeneic bone marrow transplantation on pulmonary function in 80
      children in a single paediatric centre.
AB  - We retrospectively reviewed the results of serial pulmonary function tests (PFT)
      after allogeneic bone marrow transplantation (BMT) performed in 80 children at a
      single institution over a 16-year period. We looked for associations linking PFT
      results to graft-versus-host disease (GVHD), conditioning regimen (total body
      irradiation (TBI) vs busulphan), and cytomegalovirus immune status. The median
      follow-up after BMT was 4 years. At 2 years after BMT, significant declines were
      found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1),
      as compared to baseline. Both FEV1 and the FEV1/FVC ratio showed significantly
      greater reductions in the group conditioned with busulphan (n=22) than in the
      group conditioned with TBI (n=49) and were significantly lower in the patients
      with (n=16) than without (n=64) chronic GVHD. Busulphan may be associated with
      greater long-term lung toxicity than TBI. The relevance of this finding to
      selection of conditioning regimens for BMT should be examined in the light of the
      overall pattern of side effects. Chronic GVHD was associated with airway
      obstruction.

PMID- 15170173
TI  - World Marrow Donor Association: international standards for unrelated
      hematopoietic stem cell donor registries.
AB  - World Marrow Donor Association standards are aimed at enhancing the quality of
      unrelated volunteer donor hematopoietic stem cell registries assisting transplant
      physicians in the international search for unrelated donors for their patients.
      The standards cover: (1) general organization of registries; (2) donor
      recruitment; (3) donor characterization; (4) information technology; (5)
      facilitation of search requests; (6) second/subsequent donations; (7)
      collection/processing/transport of stem cells; (8) follow-up of patient/donor;
      and (9) financial/legal responsibilities.

PMID- 15170174
TI  - A special report: suggested procedures for international unrelated donor search
      from the donor registries and quality assurance working groups of the World
      Marrow Donor Association (WMDA).
AB  - This special report details the World Marrow Donor Association's recommended
      procedures regarding the international search for an unrelated donor for
      hematopoietic stem cell transplantation. The responsibilities of the national
      hubs, transplant center and donor registry staff are outlined for all actions
      associated with the preliminary search, formal search, donor confirmatory typing
      and final donor selection.

PMID- 15170176
TI  - High-dose chemotherapy with autologous peripheral blood stem cell transplantation
      for bone and soft-tissue sarcomas.
AB  - The role of high-dose chemotherapy (HDCT) with PBSCT in the treatment of bone and
      soft-tissue sarcomas is not established. In total, 27 patients (15 female, median
      age at TPL 30.6 years (range: 13-59)) were analyzed (Ewing sarcoma family n=8,
      osteosarcoma n=6, MPNST (malignant peripheral nerve sheath tumor) n=4, synovial
      sarcoma n=3, liposarcoma n=2, leiomyosarcoma n=2, rhabdomyosarcoma n=1,
      meningosarcoma n=1). Following chemotherapy and surgery complete remission (CR)
      (n=9), partial remission (PR) (n=10), stable disease (SD) (n=2) and progressive
      disease (PD) (n=6) were reached prior HDCT. Different HDCT conditioning regimens
      were used. One patient died due to cardiac arrest after HDCT. Except hematologic
      side effects, no WHO grade III-IV complications were observed. Four patients died
      within 6 months due to PD, disease recurred in another seven patients and led to
      death, 15 patients are alive with/without disease. The median progression-free
      survival (PFS) is 12.0 months (range: 0-58), in nine CR patients median PFS is
      25.8 months (range: 3-58). Although the role of HDCT in the treatment of sarcomas
      is not defined, a subgroup of patients who achieved CR before HDCT could benefit
      from this therapy.

PMID- 15170175
TI  - Impact of circulating bone-resorbing cytokines on the subsequent bone loss
      following bone marrow transplantation.
AB  - Cytokines including IL-6 and TNF-alpha play an important role in the pathogenesis
      of postmenopausal osteoporosis. However, the relationship between changes in the
      cytokine levels and subsequent bone loss in patients undergoing a bone marrow
      transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic
      BMT were prospectively investigated. The bone turnover markers and the serum
      cytokines were measured before BMT and serially after BMT. Bone mineral density
      (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar
      spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased
      by 12.3%. The serum IL-6 and TNF-alpha levels increased until 2 and 3 weeks after
      BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6
      and TNF-alpha levels increased by post-BMT 3 weeks. The lumbar BMD decreased
      significantly as the cumulative prednisolone and cyclosporine dose increased.
      Patients with GVHD > or =grade II had higher lumbar bone loss than patients with
      GVHD <grade I. In conclusion, immunosuppressants, GVHD occurrence and increase in
      bone-resorbing cytokines in the early post-BMT period were associated with later
      bone loss after BMT. Further studies are needed to elucidate the precise
      mechanism.

PMID- 15170177
TI  - Sequence-specific DNA binding determined by contacts outside the helix-turn-helix
      motif of the ParB homolog KorB.
AB  - The KorB protein of the broad-host-range plasmid RP4 acts as a multifunctional
      regulator of plasmid housekeeping genes, including those responsible for
      replication, maintenance and conjugation. Additionally, KorB functions as the
      ParB analog of the plasmid's partitioning system. The protein structure consists
      of eight helices, two of which belong to a predicted helix-turn-helix motif. Each
      half-site of the palindromic operator DNA binds one copy of the protein in the
      major groove. As confirmed by mutagenesis, recognition specificity is based
      mainly on two side chain interactions outside the helix-turn-helix motif with two
      bases next to the central base pair of the 13-base pair operator sequence. The
      surface of the KorB DNA-binding domain mirrors the overall acidity of KorB,
      whereas DNA binding occurs via a basic interaction surface. We present a model of
      KorB, including the structure of its dimerization domain, and discuss its
      interactions with the highly basic ParA homolog IncC.

PMID- 15170178
TI  - Kinetic analysis of the RNAi enzyme complex.
AB  - The siRNA-directed ribonucleoprotein complex, RISC, catalyzes target RNA cleavage
      in the RNA interference pathway. Here, we show that siRNA-programmed RISC is a
      classical Michaelis-Menten enzyme in the presence of ATP. In the absence of ATP,
      the rate of multiple rounds of catalysis is limited by release of the cleaved
      products from the enzyme. Kinetic analysis suggests that different regions of the
      siRNA play distinct roles in the cycle of target recognition, cleavage, and
      product release. Bases near the siRNA 5' end disproportionately contribute to
      target RNA-binding energy, whereas base pairs formed by the central and 3'
      regions of the siRNA provide a helical geometry required for catalysis. Finally,
      the position of the scissile phosphate on the target RNA seems to be determined
      during RISC assembly, before the siRNA encounters its RNA target.

PMID- 15170179
TI  - Crystal structure of the C-terminal clock-oscillator domain of the cyanobacterial
      KaiA protein.
AB  - KaiA, KaiB and KaiC constitute the circadian clock machinery in cyanobacteria,
      and KaiA activates kaiBC expression whereas KaiC represses it. Here we show that
      KaiA is composed of three functional domains, the N-terminal amplitude-amplifier
      domain, the central period-adjuster domain and the C-terminal clock-oscillator
      domain. The C-terminal domain is responsible for dimer formation, binding to
      KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations.
      The X-ray crystal structure at a resolution of 1.8 A of the C-terminal clock
      oscillator domain of KaiA from the thermophilic cyanobacterium
      Thermosynechococcus elongatus BP-1 shows that residue His270, located at the
      center of a KaiA dimer concavity, is essential to KaiA function. KaiA binding to
      KaiC probably occurs via the concave surface. On the basis of the structure, we
      predict the structural roles of the residues that affect circadian oscillations.

PMID- 15170180
TI  - Strongly enhanced current densities in superconducting coated conductors of
      YBa2Cu3O7-x + BaZrO3.
AB  - There are numerous potential applications for superconducting tapes based on
      YBa(2)Cu(3)O(7-x) (YBCO) films coated onto metallic substrates. A long
      established goal of more than 15 years has been to understand the magnetic-flux
      pinning mechanisms that allow films to maintain high current densities out to
      high magnetic fields. In fact, films carry one to two orders of magnitude higher
      current densities than any other form of the material. For this reason, the idea
      of further improving pinning has received little attention. Now that
      commercialization of YBCO-tape conductors is much closer, an important goal for
      both better performance and lower fabrication costs is to achieve enhanced
      pinning in a practical way. In this work, we demonstrate a simple and
      industrially scaleable route that yields a 1.5-5-fold improvement in the in
      magnetic-field current densities of conductors that are already of high quality.

PMID- 15170181
TI  - Look before you leap.

PMID- 15170182
TI  - Shift in NIH focus fuels basic researchers' fears.

PMID- 15170184
TI  - Newly expanded European Union faces growing pains.

PMID- 15170186
TI  - Japan's laws on recombinant DNA tie researchers' hands.

PMID- 15170188
TI  - Animal activists take aim at Columbia University's primate program.

PMID- 15170189
TI  - Collaboration may be the cure for what ails drug development.

PMID- 15170191
TI  - Yusuke Nakamura.

PMID- 15170192
TI  - PET concerns in bevacizumab treatment.

PMID- 15170194
TI  - Modern science versus the stigma of obesity.

PMID- 15170195
TI  - When are research risks reasonable in relation to anticipated benefits?

PMID- 15170197
TI  - Selecting the right patient for tumor therapy.

PMID- 15170198
TI  - TORward AKTually useful mouse models.

PMID- 15170200
TI  - Magic bullets melt fat.

PMID- 15170201
TI  - The two-timing thyroid.

PMID- 15170202
TI  - Balancing muscle hypertrophy and atrophy.

PMID- 15170203
TI  - Tolerance tag team.

PMID- 15170204
TI  - Cheating death in the liver.

PMID- 15170210
TI  - Isolated small intestinal segments support auxiliary livers with maintenance of
      hepatic functions.
AB  - We determine here the functional integrity of auxiliary livers in containers
      fashioned from the small intestine. Liver microfragments from dipeptidyl
      peptidase 4 (DPP4)-deficient rats were transplanted into syngeneic normal animals
      with isolated intestinal segments characterized by mucosal denudation but intact
      vascular supply. Transplanted liver fragments were restored to confluent tissue
      with normal hepatic architecture and development of DPP4-positive vessels,
      indicating angiogenesis and revascularization. Auxiliary liver units expressed
      multiple hepatotrophic and angiogenic genes, and transplanted tissues remained
      intact for up to the 6-week duration of the studies with neither ischemic injury
      nor significant hepatocellular proliferation. Hepatic metabolic, transport and
      synthetic functions were preserved in auxiliary livers, including uptake and
      biliary excretion of (99m)Tc-mebrofenin in syngeneic recipients of liver from
      F344 rats, as well as secretion of albumin in allografted Nagase analbuminemic
      rats. This ability to produce functionally competent auxiliary livers in
      vascularized intestinal segments offers therapeutic potential for liver disease
      and genetic deficiency.

PMID- 15170211
TI  - Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes
      that differ in self-renewal capacity.
AB  - Emerging evidence suggests cancer stem cells sustain neoplasms; however, little
      is understood of the normal cell initially targeted and the resultant cancer stem
      cells. We show here, by tracking individual human leukemia stem cells (LSCs) in
      nonobese diabetic-severe combined immunodeficiency mice serially transplanted
      with acute myeloid leukemia cells, that LSCs are not functionally homogeneous
      but, like the normal hematopoietic stem cell (HSC) compartment, comprise distinct
      hierarchically arranged LSC classes. Distinct LSC fates derived from
      heterogeneous self-renewal potential. Some LSCs emerged only in recipients of
      serial transplantation, indicating they divided rarely and underwent self-renewal
      rather than commitment after cell division within primary recipients.
      Heterogeneity in LSC self-renewal potential supports the hypothesis that they
      derive from normal HSCs. Furthermore, normal developmental processes are not
      completely abolished during leukemogenesis. The existence of multiple stem cell
      classes shows the need for LSC-targeted therapies.

PMID- 15170212
TI  - Localization of Rac2 via the C terminus and aspartic acid 150 specifies
      superoxide generation, actin polarity and chemotaxis in neutrophils.
AB  - Despite having a high degree of sequence similarity, the Rho guanosine
      triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we
      demonstrate that the unique Rac2 localization and functions in neutrophils are
      regulated by two separate C-terminal motifs, the hypervariable domain and
      aspartic acid 150, one of which has not previously been linked to the function of
      Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization
      on Rac2 activity in these same cells, demonstrating a degree of crosstalk between
      two closely related Rho GTPases. Thus, we have defined specific sequences in Rac
      that specify subcellular localization and determine the specificity of Rac2 in
      neutrophil chemotaxis and superoxide generation.

PMID- 15170213
TI  - Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest
      derived enteric neuron precursors.
AB  - Hirschsprung disease (HSCR) is a multigenic, congenital disorder that affects 1
      in 5,000 newborns and is characterized by the absence of neural crest-derived
      enteric ganglia in the colon. One of the primary genes affected in HSCR encodes
      the G protein-coupled endothelin receptor-B (EDNRB). The expression of Ednrb is
      required at a defined time period during the migration of the precursors of the
      enteric nervous system (ENS) into the colon. In this study, we describe a
      conserved spatiotemporal ENS enhancer of Ednrb. This 1-kb enhancer is activated
      as the ENS precursors approach the colon, and partial deletion of this enhancer
      at the endogenous Ednrb locus results in pigmented mice that die postnatally from
      megacolon. We identified binding sites for SOX10, an SRY-related transcription
      factor associated with HSCR, in the Ednrb ENS enhancer, and mutational analyses
      of these sites suggested that SOX10 may have multiple roles in regulating Ednrb
      in the ENS.

PMID- 15170214
TI  - Instability of Hes7 protein is crucial for the somite segmentation clock.
AB  - During somitogenesis, a pair of somites buds off from the presomitic mesoderm
      every 2 hours in mouse embryos, suggesting that somite segmentation is controlled
      by a biological clock with a 2-hour cycle. Expression of the basic helix-loop
      helix factor Hes7, an effector of Notch signaling, follows a 2-hour oscillatory
      cycle controlled by negative feedback; this is proposed to be the molecular basis
      for the somite segmentation clock. If the proposal is correct, this clock should
      depend crucially on the short lifetime of Hes7. To address the biological
      importance of Hes7 instability, we generated mice expressing mutant Hes7 with a
      longer half-life (approximately 30 min compared with approximately 22 min for
      wild-type Hes7) but normal repressor activity. In these mice, somite segmentation
      and oscillatory expression became severely disorganized after a few normal cycles
      of segmentation. We simulated this effect mathematically using a direct
      autorepression model. Thus, instability of Hes7 is essential for sustained
      oscillation and for its function as a segmentation clock.

PMID- 15170215
TI  - Homogeneous detection of unamplified genomic DNA sequences based on colorimetric
      scatter of gold nanoparticle probes.
AB  - Nucleic acid diagnostics is dominated by fluorescence-based assays that use
      complex and expensive enzyme-based target or signal-amplification procedures.
      Many clinical diagnostic applications will require simpler, inexpensive assays
      that can be done in a screening mode. We have developed a 'spot-and-read'
      colorimetric detection method for identifying nucleic acid sequences based on the
      distance-dependent optical properties of gold nanoparticles. In this assay,
      nucleic acid targets are recognized by DNA-modified gold probes, which undergo a
      color change that is visually detectable when the solutions are spotted onto an
      illuminated glass waveguide. This scatter-based method enables detection of
      zeptomole quantities of nucleic acid targets without target or signal
      amplification when coupled to an improved hybridization method that facilitates
      probe-target binding in a homogeneous format. In comparison to a previously
      reported absorbance-based method, this method increases detection sensitivity by
      over four orders of magnitude. We have applied this method to the rapid detection
      of mecA in methicillin-resistant Staphylococcus aureus genomic DNA samples.

PMID- 15170216
TI  - Routing of spike series by dynamic circuits in the hippocampus.
AB  - Recurrent inhibitory loops are simple neuronal circuits found in the central
      nervous system, yet little is known about the physiological rules governing their
      activity. Here we use simultaneous somatic and dendritic recordings in rat
      hippocampal slices to show that during a series of action potentials in pyramidal
      cells recurrent inhibition rapidly shifts from their soma to the apical
      dendrites. Two distinct inhibitory circuits are sequentially recruited to produce
      this shift: one, time-locked with submillisecond precision to the onset of the
      action potential series, transiently inhibits the somatic and perisomatic regions
      of pyramidal cells; the other, activated in proportion to the rate of action
      potentials in the series, durably inhibits the distal apical dendrites. These two
      operating modes result from the synergy between pre- and postsynaptic properties
      of excitatory synapses onto recurrent inhibitory neurons with distinct projection
      patterns. Thus, the onset of a series of action potentials and the rate of action
      potentials in the series are selectively captured and transformed into different
      spatial patterns of recurrent inhibition.

PMID- 15170218
TI  - Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation.
AB  - Preinvasive mammary pathologies in humans and rat chemical carcinogenesis model
      systems have an increased microvascular density relative to normal tissue. This
      suggests the possibility of preventing invasive breast cancer by inhibiting
      angiogenesis. Vascular endothelial cell growth factor (VEGF) is a potent
      angiogenic growth factor, commonly involved in tumor-induced angiogenesis. Here,
      we show that both VEGF and VEGFR2 expression increase with histological
      progression to invasive disease in the rat 7,12-dimethylbenz[a]anthracene (DMBA)
      model. Other VEGF receptors, VEGFR1, neuropilin 1 and neuropilin 2, are
      constitutively expressed throughout progression. To examine whether VEGF
      signaling is functionally relevant to tumor-induced endothelial tubule formation
      in vitro and for tumor formation in vivo, we utilized the VEGFR2 inhibitor,
      ZD6474. In vitro endothelial cell tubulogenesis induced by isolated mammary
      organoids or carcinoma in situ from DMBA-treated rats is inhibited by ZD6474, in
      a dose-dependent fashion. The administration of ZD6474 to DMBA-treated rats
      inhibits the formation of atypical ductal hyperplasia and carcinoma in situ by
      greater than 95% (P < 0.05), when administered 1 week or 6 weeks post-DMBA
      initiation. Invasive disease was absent in all ZD6474 cohorts. These data support
      the hypothesis that progression of DMBA-induced preinvasive mammary pathologies
      to palpable disease requires angiogenesis via a VEGF-dependent mechanism.

PMID- 15170217
TI  - Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+
      channels.
AB  - High-voltage-activated Ca2+ channels are essential for diverse biological
      processes. They are composed of four or five subunits, including alpha1, alpha2
      delta, beta and gamma (ref. 1). Their expression and function are critically
      dependent on the beta-subunit, which transports alpha1 to the surface membrane
      and regulates diverse channel properties. It is believed that the beta-subunit
      interacts with alpha1 primarily through the beta-interaction domain (BID), which
      binds directly to the alpha-interaction domain (AID) of alpha1; however, the
      molecular mechanism of the alpha1-beta interaction is largely unclear. Here we
      report the crystal structures of the conserved core region of beta3, alone and in
      complex with AID, and of beta4 alone. The structures show that the beta-subunit
      core contains two interacting domains: a Src homology 3 (SH3) domain and a
      guanylate kinase (GK) domain. The AID binds to a hydrophobic groove in the GK
      domain through extensive interactions, conferring extremely high affinity between
      alpha1 and beta-subunits. The BID is essential both for the structural integrity
      of and for bridging the SH3 and GK domains, but it does not participate directly
      in binding alpha1. The presence of multiple protein-interacting modules in the
      beta-subunit opens a new dimension to its function as a multi-functional protein.

PMID- 15170222
TI  - Three ATP-binding cassette transporter genes, Abca14, Abca15, and Abca16, form a
      cluster on mouse Chromosome 7F3.
AB  - We have identified and cloned three mouse genes that belong to the ABCA subfamily
      of ATP-binding cassette (ABC) transporters. These three genes are arranged in a
      tandem head-to-tail cluster spanning about 300 kb on mouse Chromosome (Chr) 7F3.
      Phylogenetic analysis indicates that although the three genes are related to
      human and mouse ABCA3, they are not orthologs of any of the current list of 48
      human ABC genes and were, therefore, named Abca14, Abca15, and Abca16. The coding
      region of each gene is split into 31 exons, has an open reading frame of more
      than 1600 amino acids, and encodes a full transporter molecule with two
      nucleotide-binding folds (NBF) and two transmembrane domains (TMD). All three
      genes are predominantly expressed in testis, which suggests that they may perform
      special functions in testicular development or spermatogenesis. Interestingly,
      the human genome contains only fragments (less than ten exons) of at least two
      different ABC genes in the syntenic region on Chromosome 16p12 that are scattered
      among other, unrelated genes and are not capable of coding functional ABC
      transporters.

PMID- 15170223
TI  - Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a
      (Na(v)1.6) and a genetically linked retinal mutation, rd13.
AB  - The goal of The Jackson Laboratory Neuroscience Mutagenesis Facility is to
      generate mouse models of human neurological disease. We describe three new models
      obtained from a three-generation screen for recessive mutations. Homozygous
      mutant mice from lines nmf2 and nmf5 exhibit hind limb paralysis and juvenile
      lethality. Homozygous nmf58 mice exhibit a less severe movement disorder that
      includes sustained dystonic postures. The mutations were mapped to the distal
      region of mouse Chromosome (Chr) 15. Failure to complement a mutant allele of a
      positional candidate gene, Scn8a, demonstrated that the mutations are new alleles
      of Scn8a. Missense mutations of evolutionarily conserved residues of the sodium
      channel were identified in the three lines, with the predicted amino acid
      substitutions N1370T, I1392F, and L1404H. These residues are located within the
      pore loop of domain 3 of sodium channel Na(v)1.6. The lethal phenotypes suggest
      that the new alleles encode proteins with partial or complete loss of function.
      Several human disorders are caused by mutation in the pore loop of domain 3 of
      paralogous sodium channel genes. Line nmf5 contains a second, independent
      mutation in the rd13 locus that causes a reduction in cell number in the outer
      nuclear layer of the retina. rd13 was mapped to the distal 4 Mb of Chr 15. No
      coding or splice site mutations were detected in Pde1b, a candidate gene for
      rd13. The generation of three independent Scn8a mutations among 1100 tested G3
      families demonstrates that the Scn8a locus is highly susceptible to ENU
      mutagenesis. The new alleles of Scn8a will be valuable for analysis of sodium
      channel physiology and disease.

PMID- 15170224
TI  - Dissecting complex genetic interactions that influence the Engrailed-1 limb
      phenotype.
AB  - Engrailed-1, a homeobox containing transcriptional repressor, is known to play an
      important role in the development of the vertebrate limb. In its absence, mouse
      limbs develop with improper specification of dorsal identity and digit
      abnormalities. We report here that specific malformations in the mutant limb are
      dependent on strain background. We have subdivided these defects on the basis of
      morphology to define five independent traits. Each of these shows marked
      differences in prevalence among the 129/S1 and C57BL/6J strains carrying the
      En1(hd) mutation. In a genome-wide scan using SSLP markers, we have determined
      the location of one significant modifier and several additional suggestive loci
      responsible for these traits, each a facet of the En1(-/-) phenotype. We propose
      this type of sensitized genetic screen as a model approach for the discovery and
      mapping of quantitative loci that affect the subtle details of limb pattern
      formation.

PMID- 15170226
TI  - Human BAC-mediated rescue of the Friedreich ataxia knockout mutation in
      transgenic mice.
AB  - Three independent transgenic mouse lines were generated with the human Friedreich
      ataxia gene, FRDA, in an 188-kb bacterial artificial chromosome (BAC) genomic
      sequence. Three copies of the transgene per diploid mouse genome were integrated
      in a single site in each mouse line. Transgenic mice were mated with mice
      heterozygous for a knockout mutation of the murine Frda gene, to generate mice
      homozygous for the Frda knockout mutation and hemizygous or homozygous for the
      human transgene. Rescue of the embryonic lethality that is associated with
      homozygosity for the Frda knockout mutation was observed in all three lines.
      Rescued mice displayed normal behavioral and biochemical parameters. RT-PCR
      analysis demonstrated that human FRDA mRNA is expressed in all the lines. The
      relative expression of the human FRDA and mouse Frda genes showed a similar
      pattern in different tissues in all three lines, indicating position-independent
      control of expression of the human FRDA transgene. However, large differences in
      the human:mouse mRNA ratio were observed between different tissues in all three
      lines. The human transgene is expressed at much higher levels in the brain,
      liver, and skeletal muscle than the endogenous gene, while expression of the
      human transgene in blood is only 25-30% of the mouse gene. These studies will
      facilitate the development of humanized mouse models of Friedreich ataxia through
      introduction of a GAA trinucleotide expansion or specific known point mutations
      in the normal human FRDA locus and the study of the regulation of gene expression
      from the FRDA locus.

PMID- 15170225
TI  - Mapping a chromosomal locus for valproic acid-induced exencephaly in mice.
AB  - Human neural tube defects (NTDs) are among the most common congenital defects.
      They have a highly heterogeneous etiology, and, in addition to those seen in
      association with genetic syndromes, there are also NTDs induced by pharmaceutical
      compounds in utero, such as the widely used anti-epileptic drug valproic acid
      (VPA). Although familial studies have suggested a genetic contribution to VPA
      induced NTDs, this trait has not been adequately studied, nor have the
      responsible genetic factors been identified. We generated a series of mouse
      crosses and backcrosses using the highly inbred SWV/Fnn and C57BL/6J strains, in
      order to identify possible chromosomal loci contributing to VPA sensitivity. When
      exposed to a high dose of sodium VPA (600 mg/kg) via maternal intraperitoneal
      injection on gestational day E8.5, the fetuses manifested exencephaly in a strain
      dependent manner. Our data show an autosomal recessive trait, plus a gender
      related effect or an overall X-Chromosome (Chr) effect, as being primarily
      responsible for determining sensitivity to VPA-induced exencephaly. Genome
      scanning and further linkage analysis of 131 exencephalic backcross fetuses
      identified a major locus linked to D7Mit285 (p < 2 x 10(-6)), exceeding the
      threshold for significant linkage. These results suggest a major chromosomal
      locus associated with the sensitivity to VPA-induced exencephaly in mice.

PMID- 15170227
TI  - Identification and characterization of a novel mouse prion gene allele.
AB  - The major determinant of prion disease incubation time in mice is thought to be
      the amino acid sequence of the prion protein. Two alleles of the mouse prion gene
      ( Prnp) have been described, where Prnp(a) (Leu-108, Thr-189) and Prnp(b) (Phe
      108, Val-189) are associated with short and long incubation times, to defined
      prion strains, respectively. As part of a survey of inbred mouse lines, the prion
      gene open reading frame was sequenced and revealed a new allele, Prnp(c) (Phe
      108, Thr-189), in the strain MAI/Pas. To study the influence of Prnp(c)
      independently of the MAI/Pas genetic background, we generated a congenic line in
      which Prnp(c) was bred onto the C57BL/6JOlaHsd background. Following
      intracerebral inoculation with Chandler/RML scrapie prions, the congenic mice
      showed an increased mean incubation time relative to C57BL/6JOlaHsd, of over 100
      days. However, no differences were observed in the intensity and pattern of PrP
      immunoreactivity deposition or spongiosis. We conclude that the new allele,
      Prnp(c), modulates incubation time but not neuropathology and that the previous
      classification of mice into two distinct groups based on incubation time and Prnp
      genotype should now be revised.

PMID- 15170228
TI  - Confirmation and dissection of QTL controlling resistance to malaria in mice.
AB  - We developed an F(11) AIL population from an F(1) cross of A/J (susceptible) and
      C57BL/6J (resistant) mouse strains. One thousand F(11) mice were challenged with
      P.c. chabaudi 54X, and 340 mice selected from the phenotypic extremes for
      susceptibility and resistance were genotyped for microsatellite markers on
      Chromosomes (Chrs) 5, 8, and 17. QTL originally detected in backcross and F(2)
      populations were confirmed on the three chromosomes within narrower genomic
      regions, by maximum likelihood and regression analyses. Each of the previously
      mapped QTL on Chrs 5 and 17 resolved into two linked QTLs. The distal and
      proximal QTLs on Chrs 5 and 17, respectively, map to the previously reported QTL.

PMID- 15170229
TI  - Isolation from the horse genome of a new DNA transposon belonging to the Tigger
      family.
AB  - Tigger elements are human DNA transposons homologous to the pogo element of
      Drosophila melanogaster. They contain an open reading frame for a transposase
      very similar to the major mammalian centromere protein CENP-B. We found in the
      horse genome a DNA element ( Ecatig3) sharing 88% homology with human Tigger3.
      The presence of Tigger elements in the horse genome confirms previous data that
      date these elements before the divergence between Perissodactyla and Primates (80
      90 Myr ago). Copy number evaluation indicates that the horse element is much more
      abundant than its human counterpart. Southern blot analysis demonstrates that
      Ecatig3 elements are extremely homogeneous; this may indicate that the evolution
      of this DNA transposon has been driven by some kind of selection and has not been
      neutral.

PMID- 15170230
TI  - Development and implementation of a database system to manage a large-scale mouse
      ENU-mutagenesis program.
AB  - A mouse ENU-mutagenesis program at RIKEN GSC has been initiated to conduct a
      large-scale, genome-wide, early- and late-onset phenotypic screen of mutant mice.
      We screened about a hundred mice every week with a comprehensive set of phenotype
      assays including behavioral tests based on a modified SHIRPA protocol, blood
      tests (both clinical biochemical testing and hemogram), and measurement of
      locomotor activity in their home cages. To manage the entire program, we
      developed a client/server architecture database system and named it MUSDB
      (Mutagenesis Universal Support DataBase). It manages mouse husbandry, mating
      protocols, procedures for ENU injection and phenotypic screens, phenotype
      inheritance tests, preservation of sperm and organs, and other materials
      generated during the program. We have implemented MUSDB in quite a large-scale
      system that includes 150 client computers. It has, helped reduce typographical
      errors and provided simple and efficient operation via its front-end user
      interface. It significantly contributed to the communication within and between
      workgroups in the program and in the accumulation of various phenotypic and
      inheritance data.

PMID- 15170231
TI  - Regulation of the htpX gene of Xylella fastidiosa and its expression in E. coli.
AB  - Xylella fastidiosa was the first phytopathogen to be completely sequenced, and
      its genome revealed several interesting features to be used in functional
      studies. In the present work, the htpX gene, which encodes a protein involved in
      the heat shock response in other bacteria, was analyzed by RT-PCR by using cells
      derived from different cultural conditions. This gene was induced after a
      temperature upshift to 37 degrees C after growth in minimal medium, XDM, but
      showed constitutive expression in rich medium or in XDM plus plant extracts.
      Sequences upstream to the htpX gene, containing a putative regulatory region,
      were also transferred to E. coli, and the thermoregulation was maintained in the
      new host, since it was constitutively transcribed at 37 degrees C or 45 degrees C
      in all culture media tested, but not at 28 degrees C in minimal culture medium.
      The gene was also cloned into the expression vector pET32Xa/LIC, and the
      expression of the corresponding protein was confirmed by Western blotting.

PMID- 15170232
TI  - rpoS gene expression in carbon-starved cultures of the Polyhydroxyalkanoate
      accumulating species Pseudomonas oleovorans.
AB  - The expression of the rpoS gene during PHA depolymerization was monitored in
      Pseudomonas oleovorans GPo1 and its mutant defective in PHA degradation by
      analyzing the tolerance to oxidative and thermal stresses and the RpoS
      intracellular content. An increase in the tolerance to H2O2 and heat shock was
      observed coincidentally with PHA degradation. Western blotting experiments
      performed in carbon-starved cultures showed that the RpoS levels were higher in
      the wild type than in the mutant strain. Complementation of the phaZ mutation
      restores the wild-type RpoS levels. These results suggest a probable association
      between PHA depolymerization and the stress tolerance phenotype controlled by
      RpoS.

PMID- 15170233
TI  - The delta subunit of RNA polymerase functions in sporulation.
AB  - Purified RNA polymerase from Bacillus subtilis and other Gram-positive organisms
      contains a novel subunit designated delta encoded by the rpoE gene. There is no
      distinctive phenotype of strains with a disruption of this gene, so the function
      of delta is very subtle or redundant. We have found, however, that suppression of
      a block in sporulation of B. subtilis at early stage III owing to disruption of
      the pdhC gene encoding the E2 subunit of pyruvate dehydrogenase (PDH) was
      attributable to a Tn10 insertion in the rpoE gene. An independent disruption of
      this gene also caused suppression. An earlier sporulation block due to absence of
      the E1beta subunit of PDH was not suppressed. This specific suppression indicates
      that the delta subunit does have some direct or indirect role in sporulation,
      probably in the transcription of selected genes at stage II-III of sporulation,
      which is critical but only when there is functional E2.

PMID- 15170235
TI  - Detection of LEE 4 region-encoded genes from different enteropathogenic and
      enterohemorrhagic Escherichia coli serotypes.
AB  - The LEE 4 genes sepL, espA, espD, espB, and espF were detected in 50 strains of
      typical and atypical enteropathogenic (EPEC) and enterohemorrhagic (EHEC)
      Escherichia coli by PCR. sepL was amplified in 90%, espA in 94%, espB in 50%,
      espD in 40%, and espF in 78% of all strains, employing prototype EPEC-based
      primers. With O26:H(-)-based primers, espB was detected in all O26 strains, and
      O157:H7-specific primers amplified espD and espB among all O55:H7 and O157:H7
      strains. Our results indicated that espA and sepL should be more conserved
      between different EPEC and EHEC serotypes, while espB, espD, and espF should be
      more diverse. Apparently this variation is related to serogroup or serotype, but
      sequencing assays are necessary to confirm such conservation/diversity and their
      association with serogroup or serotype. Secreted protein analyses of espA, espD,
      and espB PCR-negative strains demonstrated that their encoded proteins present
      distinct immunological types, reflecting the genetic variability of those genes.

PMID- 15170234
TI  - Characterization of Penicillium species isolated from grape berries by their
      internal transcribed spacer (ITS1) sequences and by gas chromatography-mass
      spectrometry analysis of geosmin production.
AB  - Geosmin (trans-1,10-dimethyl-trans-9-decalol), an earthy-musty compound, has been
      identified in wines and in grape juice, in which its presence is highly
      detrimental to the aromatic quality. Geosmin has a biological origin, and the
      analysis of rotten grape microflora has been done on two grape varieties
      (Semillon, Cabernet Sauvignon) from six parcels of the Bordeaux region over 3
      years (1999, 2000, 2001). Forty-three Penicillium-related species have been
      analyzed by gas chromatography-mass spectrometry (GC-MS) for their geosmin
      production. GC-MS analysis has demonstrated that the earthy odor was always
      correlated with the presence of geosmin. Phenotypic characterization of
      Penicillium spp. being ambiguous, a molecular characterization by rDNA internal
      transcribed spacer (ITS1) sequencing was performed for all strains. The results
      evidenced that all strains producing geosmin belonged to only one species, P.
      expansum, and that the other strains, not producing geosmin, belonged to three
      species: P. purpurogenum, P. thomii, and Talaromyces wortmanii.

PMID- 15170236
TI  - Isolation and characterization of Citrobacter strain HPC255 for broad-range
      substrate specificity for chlorophenols.
AB  - This study aims at development of an approach for selection of strain, which has
      capability for oxidation of broad-range of chloro-substitute phenols. A multiplex
      PCR was optimized targeting loci involved in phenol and chlorophenol degradation,
      which was used to select activated sludge samples and also to assess the
      degradative genotype of isolates. The isolated strains were screened on the basis
      of RAPD analysis. In parallel, physiological experiments were carried out with
      activated sludge samples and isolated bacteria by respirometric analysis. Based
      on cluster analysis of RAPD pattern and respirometric data, the isolate G20 was
      selected and identified by using 16S rDNA sequence analysis as Citrobacter
      freundii strain HPC255. The strain could oxidize different substituted
      chlorophenol molecules. Such strains could provide the pool of intermediates,
      which can further be degraded by the associated population, thus helping in
      maintaining the synergistic association of catabolic activity in activated
      sludge.

PMID- 15170237
TI  - Roles of poly(3-hydroxybutyrate) depolymerase and 3HB-oligomer hydrolase in
      bacterial PHB metabolism.
AB  - Many poly-3-hydroxybutyrate (PHB)-degrading enzymes have been studied. But
      biological roles of 3HB-oligomer hydrolases (3HBOHs) and how PHB depolymerases
      (PHBDPs) and 3HBOHs cooperate in PHB metabolism are not fully elucidated. In this
      study, several PHBDPs and 3HBOHs from three types of bacteria were purified, and
      their substrate specificity, kinetic properties, and degradation products were
      investigated. From the results, PHBDP and 3HBOH seemed to play a role in PHB
      metabolism in three types of bacteria, as follows: (A) In Ralstonia pickettii T1,
      an extracellular PHBDP degrades extracellular PHB to various-sized 3HB-oligomers,
      which an extracellular 3HBOH hydrolyzes to 3HB-monomers. (B) In Acidovorax sp.
      SA1, an extracellular PHBDP hydrolyzes extracellular PHB to small 3HB-oligomers
      (dimer and trimer), which an intracellular 3HBOH efficiently degrades to 3HB in
      the cell. (C) In Ralstonia eutropha H16, an intracellular 3HBOH helps in the
      degradation of intracellular PHB inclusions by PHBDP.

PMID- 15170238
TI  - Nucleotide sequence variation does not relate to differences in kinetic
      properties of neutral trehalase from the insect pathogenic fungus Metarhizium
      anisopliae.
AB  - Genetic variability in a putative virulence factor, the neutral trehalase ( Ntl)
      gene, was examined in strains of the insect pathogenic fungi Metarhizium
      anisopliae and Metarhizium flavoviride by restriction fragment length
      polymorphism (RFLP). The Ntl gene was sequenced from four of these strains that
      showed dissimilar RFLP patterns. Enzyme kinetic experiments were also performed
      on the partially purified neutral trehalase in order to assess whether nucleotide
      changes in these strains related to differences in enzyme catalytic function
      (i.e., Km, Vmax, and Kcat). Finally, the Metarhizium strains were assessed in
      bioassays against waxworm larvae in order to relate nucleotide variation with Ntl
      enzyme kinetics and insect virulence. The greatest RFLP variation was observed
      with Rsa1. M. flavoviride was found to be most dissimilar in RFLP patterns when
      compared with the M. anisopliae strains. RFLP patterns for Ntl were diagnostic
      markers for previously studied genetic groups of M. anisopliae. Comparisons of
      Ntl sequences showed that the introns were found to be more variable (6.2%) than
      the exons (3.1%). Comparisons of the translated nucleotide codons showed high
      levels (91%) of synonymous sequence variation between strains. Another fraction
      of the remaining mutations was neutral, resulting in amino acid substitutions
      with similar functions. The neutral trehalase was partially purified by
      preparative isoelectric focus, revealing a single band of enzyme activity as
      assessed by analytical isoelectric focusing (pI ca. 5). Kinetic properties of the
      neutral trehalases revealed no differences between the M. anisopliae strains,
      while the M. flavovoride had a lower Kcat/Km. However, there was lower virulence
      in one strain that showed Ntl enzyme kinetic properties that were similar to the
      other strains, suggesting that factors other than neutral trehalase may be
      responsible for delimiting virulence in this insect pathogenic fungi. Although
      there is nucleotide variation in genes involved in pathogenicity, this variation
      is mostly neutral in nature, and there is strong stabilizing selection to
      maintain enzyme function.

PMID- 15170240
TI  - Sequence of the core antenna domain from the anoxygenic phototroph Heliophilum
      fasciatum: implications for diversity of reaction center type I.
AB  - Broad variation among anoxygenic reaction centers makes it essential to consider
      a wide variety when considering the origins of photosynthesis. The photosynthetic
      core antenna domain in the gene pshA from Heliophilum fasciatum was sequenced
      doubling the number of core sequences available from heliobacteria. The sequence
      shares a pattern of hydrophobicity and histidine residues with the core antenna
      domain of pshA from Heliobacillus mobilis. Sequence identity between the two pshA
      sequences was 68%, indicating heliobacterial reaction centers show similar
      diversity to photosystem I throughout cyanobacteria and plastids. Thus, the
      diversity of anoxygenic phototrophic reaction centers may be greater than
      previously thought.

PMID- 15170239
TI  - Babesia microti infection in Europe.
AB  - The majority of babesia infections in Europe are life-threatening and caused by
      Babesia divergens and B. bovis. Although Babesia microti has been detected in
      ticks from Switzerland, few if any cases of babesiosis have been caused by B.
      microti. This first reported case, diagnosed by serology, DNA detection, and
      microscopy, is additionally interesting because there appears to be coinfection
      with the Lyme disease organism, Borrelia burgdorferi.

PMID- 15170241
TI  - Low-molecular-weight, biologically active compounds from marine Pseudoalteromonas
      species.
AB  - We have examined the ability of marine Proteobacteria from the Pseudoalteromonas
      genus and Alteromonas macleodii to produce low-molecular-weight, biologically
      active compounds with antimicrobial and surface-active properties. A new marine
      bacterium, Pseudoalteromonas issachenkonii, exhibited a high level of biological
      activity and produced antifungal and hemolytic compounds. A detailed
      spectroscopic investigation based on UV, IR, high-resolution mass spectrometry,
      and 2D 1H and 13C nuclear magnetic resonance revealed that the former was indole
      2,3-dione (isatin). The chemical structure of red-brown pigment (C9H7N3OS3)
      responsible for hemolytic activity remained unclear. Four of the 15 strains
      studied (P. luteoviolacea, P. rubra, P. undina, and P. issachenkonii) produced
      cell-bound, two (P. elaykovii and P. carrageenovora) produced extracellular, and
      one strain (P. citrea) produced cell-bound and extracellular fatty acids and
      phospholipids with surface activity. Neither peptides nor glycolipids with
      surface activity were detected.

PMID- 15170242
TI  - Relationship between expression of cell surface hydrophobicity protein 1 (CSH1p)
      and surface hydrophobicity properties of Candida dubliniensis.
AB  - Candida dubliniensis and Candida albicans cause most of the oral candidiasis
      infections in AIDS patients. Unlike C. albicans, which variably expresses cell
      surface hydrophobicity (CSH) depending on environmental conditions, C.
      dubliniensis is hydrophobic under all environmental conditions. C. dubliniensis
      produces CdCSH1p, a protein related to CaCSH1p that contributes to CSH expression
      of C. albicans. We investigated whether environmental conditions affect CdCSH1p
      expression, CSH avidity, and adhesion to fibronectin (Fn). C. dubliniensis CD36
      was grown at 23 degrees C and 37 degrees C in four different media. CdCSH1p
      expression was affected by growth temperature, with cells grown at 37 degrees C
      expressing the protein, but cells grown at 23 degrees C did not. Hydrophobic
      avidity for two media was higher in cells grown at 37 degrees C than at 23
      degrees C. Cells grown at 23 degrees C were generally less adherent than 37
      degrees C-grown cells to Fn. The results suggest CdCSH1p but not hydrophobic
      avidity may have a role in adhesion of C. dubliniensis to Fn.

PMID- 15170243
TI  - Phylogenetically diverse new sulfur chemolithotrophs of alpha-proteobacteria
      isolated from Indian soils.
AB  - Five facultative sulfur chemolithotrophs were isolated from soils to study the
      diversity of sulfur lithotrophy. Phenotypic characteristics, including sulfur
      lithotrophic properties and chemotaxonomic features of the isolates, were similar
      to those of the members of the colorless sulfur bacteria. 16S rDNA sequence
      analyses rendered placing the isolates to three distinct phylogenetic clusters of
      alpha-proteobacteria. Three isolates, AS001, AS002, and KCT002, were identified
      as members of the genus Paracoccus. The strains AS001 and AS002, having identical
      16S-rDNA sequence, showed significant 16S rDNA sequence similarity (99.1%) to
      Paracoccus versutus. The strain KCT002 showed highest (98%) 16S rDNA sequence
      similarity to P. alcaliphilus and 96% similarity to the pair AS001 and AS002.
      Isolate KCT001 appeared to be closely related to Pseudaminobacter
      salicylatoxidans, although sulfur lithotrophy of P. salicylotoxidans is not
      known. The other isolate, TCK, showed almost identical 16S rDNA (99.9%) sequence
      with two recently described unclassified chemolithoautotrophic arsenite oxidizing
      strains. Physiological and chemotaxonomic characteristics and phylogenetic
      analyses of the five new strains emphasize the need of polyphasic bacterial
      taxonomy of sulfur lithotrophs.

PMID- 15170244
TI  - Analysis of sediment retention in western riverine wetlands: the Yampa River
      watershed, Colorado, USA.
AB  - We quantified annual sediment deposition, bank erosion, and sediment budgets in
      nine riverine wetlands that represented a watershed continuum for 1 year in the
      unregulated Yampa River drainage basin in Colorado. One site was studied for 2
      years to compare responses to peak flow variability. Annual mean sediment
      deposition ranged from 0.01 kg/m(2) along a first-order subalpine stream to 21.8
      kg/m(2) at a sixth-order alluvial forest. Annual mean riverbank erosion ranged
      from 3 kg/m-of-bank at the first-order site to 1000 kg/m at the 6(th)-order site.
      Total sediment budgets were nearly balanced at six sites, while net export from
      bank erosion occurred at three sites. Both total sediment deposition (R(2) =
      0.86, p < 0.01) and bank erosion (R(2) = 0.77, p < 0.01) were strongly related to
      bankfull height, and channel sinuosity and valley confinement helped to explain
      additional variability among sites. The texture and organic fraction of eroded
      and deposited sediment were relatively similar in most sites and varied among
      sites by watershed position. Our results indicate that bank erosion generally
      balances sediment deposition in riverine wetlands, and we found no distinct zones
      of sediment retention versus export on a watershed continuum. Zones of apparent
      disequilibrium can occur in unregulated rivers due to factors such as incised
      channels, beaver activity, and cattle grazing. A primary function of many western
      riverine wetlands is sediment exchange, not retention, which may operate by
      transforming materials and compounds in temporary sediment pools on floodplains.
      These results are considered in the context of the Hydrogeomorphic approach being
      implemented by the U.S. government for wetland resource management.

PMID- 15170245
TI  - Metabolic modulation by lipoplasty: a case report and invitation for
      investigators.
AB  - Metabolic modulation refers to the change in glucose metabolism that may be
      caused by the reduction in body fat after large-volume liposuction. Since the
      authors began doing liposuction in 1989, they have had several diabetic patients
      whose insulin or oral diabetic needs have been substantially reduced after
      liposuction. When the charts for these patients were reviewed, it was found that
      they had improved diets, increased exercise, and decreased weight. The authors
      were uncertain about the relation between fat removal and metabolic modulation.
      They recently had a patient whose fasting blood sugar went from 200 to 100 mg
      after large-volume liposuction, and has stayed that way for more than 1 year. In
      addition, this patient lost 60 more pounds in the year after liposuction. It
      appears that removal of fat may improve several metabolic parameters, so the
      authors have started a multicenter study to evaluate this finding.

PMID- 15170246
TI  - Two-plane injection of botulinum exotoxin A in glabellar frown lines.
AB  - Botulinum exotoxin A has been used for the treatment of glabellar frown lines.
      Despite this fact, the effect of the toxin is sometimes either partial or lost in
      a short time. The muscles responsible for frowning, the corrugator supercilii and
      depressor supercilii muscles, are attached to the periosteum in the glabellar
      region under the frontalis muscle deep in the medial aspect. The muscles then
      course laterally and superficially to insert in the skin superior to the
      eyebrows. Thus, to get a long-lasting and full effect, the exotoxin has been
      applied deeply in the medial aspect and superficially in the lateral aspect of
      the glabellar region. It is concluded that botulinum exotoxin is more effective
      when it is applied in two planes superficially and deep so that the anatomic
      course of the corrugator supercilii and the depressor supercilii muscles are
      followed.

PMID- 15170247
TI  - Amyloidosis complicating rhinophyma.
AB  - Rhinophyma is the advanced stage of acne rosacea and a source of embarrassment
      for the patient. Secondary localized cutaneous amyloidosis complicating
      rhinophyma is not reported in the literature. A patient with rhinophyma was
      treated by excision and primary closure. The histologic examination showed
      amyloidosis.

PMID- 15170248
TI  - Correction of buttock ptosis with anchoring deepithelialized skin flaps.
AB  - A new technique for correction of a buttock ptosis resulting from a degloving
      injury is presented. With this technique, the deepithelialized crescent-like zone
      in lateral thigh redundancy anchored to gluteal fascia through three separate
      incisions as used for creation of a new gluteal crease. The patient's
      satisfaction was good with long-term follow-up evaluation. Infragluteal fold
      reconstruction is achieved by reconstruction of the buttock's sustaining apparel
      through deepithelialized skin flaps anchored to deep gluteal fascia.

PMID- 15170249
TI  - Augmentation mammaplasty: where should the implant be placed?
AB  - Malposition of the prosthesis is one complication of augmentation mammaplasty.
      The most projected point of the prosthesis should be placed just behind the
      nipple to create a natural-looking breast. However, in some cases, when a
      textured surface cohesive silicone gel prosthesis with an inframammary approach
      is used, low displacement of the prosthesis is encountered within 1 year. This
      phenomenon can be seen both in subpectoral augmentation with severing of the
      muscle at the level of the inframammary fold and in subglandular augmentation
      when the patient's breast and skin are very soft and easily stretchable.
      Therefore, the elasticity of the breast should be evaluated before surgery. If
      the patients breast and skin are very soft and easily stretchable, the pocket for
      the prosthesis should be created 1 to 1.5 cm superiorly to the usual pocket for
      the prosthesis. The design of the pocket for the prosthesis should be different
      depending on the shape of the prosthesis and the elasticity of the patient's
      breasts.

PMID- 15170250
TI  - Late hematoma after breast implantation.
AB  - The case of a patient who experienced a late, spontaneous breast hematoma 9 years
      after augmentation mammaplasty in the absence of trauma or anticoagulation is
      reported. Although hematoma is not an uncommon complication in the immediate
      postoperative period, it is very rare as a late complication of breast
      implantation. A review of the literature suggested that a chronic inflammatory
      reaction to the polyurethane-coated implants used in the reported patient was the
      most likely cause for the complication.

PMID- 15170254
TI  - Phylogenetic analysis of the plant endo-beta-1,4-glucanase gene family.
AB  - Phylogenetic analysis of the endo-beta-1,4-glucanase gene family of Arabidopsis
      and other plants revealed a clear distinction in three subfamilies (alpha, beta,
      and gamma). The alpha- and beta-subfamily contains proteins believed to be
      involved in a number of physiological roles such as elongation, ripening, and
      abscission. The gamma-subfamily is composed of proteins that are predicted to
      have a membrane-spanning domain and to be localized at the plasma membrane. Some
      of these proteins have been linked to cellulose biosynthesis by serving to
      hydrolyze a lipid-linked intermediate that acts as a primer for the elongation of
      beta-glucan chains during cellulose synthesis at the plasma membrane. Similar
      glucanases are important in cellulose biosynthesis in bacteria. Searches in the
      genomes of unrelated organisms that make cellulose, such as Ciona intestinalis
      and Dictyostelium discoideum, revealed the presence of membrane-linked endo-beta
      1,4-glucanases and it is suggested that these might also have a role in cellulose
      synthesis.

PMID- 15170253
TI  - Functional constraints of alcohol dehydrogenase (ADH) of tephritidae and
      relationships with other Dipteran species.
AB  - Alcohol dehydrogenase is considered a very important enzyme in insect metabolism
      because it is involved (in its homodimeric form) in the catalysis of the
      reversible conversion of various alcohols in larval feeding sites to their
      corresponding aldehydes and ketones, thus contributing to detoxification and
      metabolic purposes. Using 14 amino acid ADH sequences recently determined in our
      laboratory, we constructed a three-dimensional (3D) model of olive fruit fly
      Bactrocera oleae ADH1 and ADH2, based on the known homologous Drosophila
      lebanonensis ADH structure, and the amino acid residues that have been proposed
      as being responsible for catalysis were located on it. Moreover, in a comparative
      study of the ADH sequences, the residues occupying characteristic positions in
      the ADH of species of the Bactrocera and Ceratitis genera (called genus-specific)
      as well as residues appearing only in ADH1 or ADH2 (called isozymic-specific)
      were defined and localized on the 3D model. All regions important for catalytic
      activity, such as those forming the substrate- and coenzyme-binding sites, are
      highly conserved in all tephritid species examined. Genus-specific amino acids
      are located on the outside of the protein, on loops and regions predicted to be
      antigenic. The higher percentage of genus-specific amino acid variation seems to
      be centered in the NAD adenine-binding site, located near the surface of the
      protein molecule. Nine of 12 isozymic-specific positions are lined along an "arc"
      on the surface of the protein, thus linking the two "monomer bases" of the dimer
      via the C-terminal interacting loops. Furthermore, the distribution of isozymic-
      and genus-specific amino acids on the monomer-monomer interface may have some
      evolutionary significance. Most amino acids predicted to be antigenic are
      positioned in peripheral regions of nonfunctional importance, but surprisingly,
      an additional antigenic region is contained within the (highly conserved in
      tephritids) C-terminal tail.

PMID- 15170256
TI  - The consistent phylogenetic signal in genome trees revealed by reducing the
      impact of noise.
AB  - Phylogenetic trees based on gene repertoires are remarkably similar to the
      current consensus of life history. Yet it has been argued that shared gene
      content is unreliable for phylogenetic reconstruction because of convergence in
      gene content due to horizontal gene transfer and parallel gene loss. Here we test
      this argument, by filtering out as noise those orthologous groups that have an
      inconsistent phylogenetic distribution, using two independent methods. The
      resulting phylogenies do indeed contain small but significant improvements. More
      importantly, we find that the majority of orthologous groups contain some
      phylogenetic signal and that the resulting phylogeny is the only detectable
      signal present in the gene distribution across genomes. Horizontal gene transfer
      or parallel gene loss does not cause systematic biases in the gene content tree.

PMID- 15170257
TI  - Presence of a bacterial-like citrate synthase gene in Tetrahymena thermophila:
      recent lateral gene transfers (LGT) or multiple gene losses subsequent to a
      single ancient LGT?
AB  - Citrate synthase is the initial enzyme in the tricarboxylic acid cycle of
      mitochondria. In plants and fungi, it is the second isozyme in the glyoxylate
      cycle of peroxisomes (or glyoxysomes), and it is also present in bacteria. Some
      of the biochemical reactions in the glyoxylate cycle of the ciliated protozoan
      Tetrahymena pyriformis depend upon mitochondrial enzymes, as T. pyriformis lacks
      some glyoxysome-specific enzymes. Here we demonstrate a new citrate synthase gene
      from Tetrahymena thermophila that is different from the mitochondrial
      counterpart. A potential peroxysome-targeted signal was detected in the N
      terminus, suggesting the localization of the enzyme in peroxysomes. Phylogenetic
      analysis placed the Tetrahymena sequence in a clade consisting of a few sequences
      from eukaryotes such as cellular slime molds and two land plants, near a green
      sulfur bacterium and many proteobacteria as a sister group but not in a
      mitochondrial clade. Southern blot analysis revealed that this type of gene was
      absent from distantly related ciliates and other species of Tetrahymena except
      for the closest species, T. mallaccensis. The scattered presence of the bacterial
      like genes among distantly related eukaryotes suggests three alternative
      interpretations of acquisition of the novel glyoxysomal citrate synthase gene via
      lateral gene transfer (LGT). (1). Some eukaryotes independently acquired the gene
      from a common bacterium or closely related bacteria via LGT. (2). A hypothetical
      eukaryote once acquired the gene, which was thereafter independently transferred
      from the eukaryote to other eukaryotes. (3). A single event of LGT (or
      duplication) occurred in a certain common ancestor of eukaryotes, followed by
      multiple losses in many eukaryotic lineages during the subsequent evolution.
      Considering the monophyly of the bacterial-like eukaryotic citrate synthase
      genes, the first model is somewhat unlikely, even though it is not impossible.
      The second and third models can rationally explain the present observation, so
      these models are discussed in some detail.

PMID- 15170255
TI  - Cobra ( Naja spp. ) nicotinic acetylcholine receptor exhibits resistance to Erabu
      sea snake ( Laticauda semifasciata) short-chain alpha-neurotoxin.
AB  - Snake alpha-neutotoxins of Elapidae venoms are grouped into two structural
      classes, short-chain and long-chain alpha-neutotoxins. While these two classes
      share many chemical and biological characteristics, there are also distinct
      dissimilarities between them, including their binding site on the nicotinic
      acetylcholine receptor (nAChR), specificity among species of Chordata, and the
      associated pharmacological effects. In the present study we test the hypothesis
      that structural motifs that evolved to confer natural resistance against
      conspecific long-chain alpha-neurotoxins in Elapidae snakes also interfere with
      the biological action of short-chain alpha-neurotoxins. We expressed functional
      nAChRs that contains segments or single residues of the Elapidae nAChR ligand
      binding domain and tested the effect of short-chain alpha-neurotoxin erabutoxin-a
      (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine
      induced currents as measured by two-microelectrode voltage clamp. Our results
      show that the Elapidae nAChR alpha subunit segment T(154)-L(208) ligand binding
      domain has an inhibitory effect on the pharmacological action of ETX-a. This
      effect is primarily attributed to the presence of glycosylation at position
      N(189). If the glycosylation is removed from the T(154)-L(208) segment, the nAChR
      will be inhibited, however, to a lesser extent than seen in the mouse. This
      effect correlates with the variations in alpha-neurotoxin sensitivity of
      different species and, importantly, reflects the evolutionary conservation of the
      binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of
      alpha-neurotoxin resistance suggests that alpha-neurotoxin-resistant nAChR
      evolved first, which permitted the evolution of snake venom alpha-neurotoxins. A
      model describing alpha-neurotoxin resistance in Elapidae snakes is presented.

PMID- 15170258
TI  - Polymorphic insertions and deletions in parabasalian enolase genes.
AB  - Insertions and deletions in gene sequences have been used as characters to infer
      phylogenetic relationships and, like any character, the information they contain
      varies in utility between different levels of evolution. In one case, the absence
      of two otherwise highly conserved deletions in the enolase genes of parabasalian
      protists has been interpreted as a primitive characteristic that suggests these
      were among the first eukaryotes. Here, semi-environmental 3'-RACE was used to
      sample enolases from parabasalia in the hindgut of the termite Zootermopsis
      angusticolis to examine the conservation of this character within the
      parabasalia. Parabasalian homologues were found to be polymorphic for these
      deletions, and the phylogeny of parabasalian enolases shows that the deletion
      possessing genes branch within deletion-lacking genes (i.e., they did not form
      two clearly distinct groups). Phylogenetic incongruence was detected in the
      carboxy-terminal third of the sequence (in the region of the deletions), but
      there is no unambiguous evidence for recombination. The polymorphism of this
      character discredits these deletions as strong evidence for the early origin of
      parabasalia, although the complex distribution makes it impossible to state
      whether parabasalian enolases were ancestrally like those of other eukaryotes.
      These observations stress the importance of strong corroborating evidence when
      considering insertion and deletion data, and raises some interesting questions
      about the apparent variation in degree of conservation of these deletions between
      different eukaryotic groups.

PMID- 15170259
TI  - Structure analysis of two Toxoplasma gondii and Neospora caninum satellite DNA
      families and evolution of their common monomeric sequence.
AB  - A family of repetitive DNA elements of approximately 350 bp-Sat350-that are
      members of Toxoplasma gondii satellite DNA was further analyzed. Sequence
      analysis identified at least three distinct repeat types within this family,
      called types A, B, and C. B repeats were divided into the subtypes B1 and B2. A
      search for internal repetitions within this family permitted the identification
      of conserved regions and the design of PCR primers that amplify almost all these
      repetitive elements. These primers amplified the expected 350-bp repeats and a
      novel 680-bp repetitive element (Sat680) related to this family. Two additional
      tandemly repeated high-order structures corresponding to this satellite DNA
      family were found by searching the Toxoplasma genome database with these
      sequences. These studies were confirmed by sequence analysis and identified: (1).
      an arrangement of AB1CB2 350-bp repeats and (2). an arrangement of two 350-bp
      like repeats, resulting in a 680-bp monomer. Sequence comparison and phylogenetic
      analysis indicated that both high-order structures may have originated from the
      same ancestral 350-bp repeat. PCR amplification, sequence analysis and Southern
      blot showed that similar high-order structures were also found in the Toxoplasma
      sister taxon Neospora caninum. The Toxoplasma genome database (http://ToxoDB.org
      ) permitted the assembly of a contig harboring Sat350 elements at one end and a
      long nonrepetitive DNA sequence flanking this satellite DNA. The region bordering
      the Sat350 repeats contained two differentially expressed sequence-related
      regions and interstitial telomeric sequences.

PMID- 15170261
TI  - Abundance, distribution, and mutation rates of homopolymeric nucleotide runs in
      the genome of Caenorhabditis elegans.
AB  - Homopolymeric nucleotide runs, also called mononucleotide microsatellites, are a
      ubiquitous, dominant, and mutagenic feature of eukaryotic genomes. A clear
      understanding of the forces that shape patterns of homopolymer evolution,
      however, is lacking. We provide a focused investigation of the abundance,
      chromosomal distribution, and mutation spectra of the four strand-specific
      homopolymer types (A, T, G, C) >or=8 bp in the genome of Caenorhabditis elegans.
      A and T homopolymers vastly outnumber G and C HPs, and the run-length
      distributions of A and T homopolymers differ significantly from G and C
      homopolymers. A scanning window analysis of homopolymer chromosomal distribution
      reveals distinct clusters of homopolymer density in autosome arms that are
      regions of high recombination in C. elegans. Dramatic biases are detected among
      closely spaced homopolymers; for instance, we observe 994 A homopolymers
      immediately followed by a T homopolymer (5' to 3') and only 8 instances of T
      homopolymers directly followed by an A homopolymer. Empirical homopolymer
      mutation assays in a set of C. elegans mutation-accumulation lines reveal an
      approximately 20-fold higher mutation rate for G and C homopolymers compared to A
      and T homopolymers. Nuclear A and T homopolymers are also found to mutate
      approximately 100-fold more slowly than mitochondrial A and T homopolymers. This
      integrative approach yields a total nuclear genome-wide homopolymer mutation rate
      estimate of approximately 1.6 mutations per genome per generation.

PMID- 15170263
TI  - Plastid sequence evolution: a new pattern of nucleotide substitutions in the
      Cucurbitaceae.
AB  - Nucleotide substitutions (i.e., point mutations) are the primary driving force in
      generating DNA variation upon which selection can act. Substitutions called
      transitions, which entail exchanges between purines (A = adenine, G = guanine) or
      pyrimidines (C = cytosine, T = thymine), typically outnumber transversions (e.g.,
      exchanges between a purine and a pyrimidine) in a DNA strand. With an increasing
      number of plant studies revealing a transversion rather than transition bias, we
      chose to perform a detailed substitution analysis for the plant family
      Cucurbitaceae using data from several short plastid DNA sequences. We generated a
      phylogenetic tree for 19 taxa of the tribe Benincaseae and related genera and
      then scored conservative substitution changes (e.g., those not exhibiting
      homoplasy or reversals) from the unambiguous branches of the tree. Neither the
      transition nor (A+T)/(G+C) biases found in previous studies were supported by our
      overall data. More importantly, we found a novel and symmetrical substitution
      bias in which Gs had been preferentially replaced by A, As by C, Cs by T, and Ts
      by G, resulting in the G-->A-->C-->T-->G substitution series. Understanding this
      pattern will lead to new hypotheses concerning plastid evolution, which in turn
      will affect the choices of substitution models and other tree-building algorithms
      for phylogenetic analyses based on nucleotide data.

PMID- 15170262
TI  - Ectopic gene conversions in four Escherichia coli genomes: increased
      recombination in pathogenic strains.
AB  - We characterized the ectopic gene conversions in the genomes of the K-12 MG1655,
      O157:H7 Sakai, O157:H7 EDL933, and CFT073 strains of E coli. Compared to the
      three pathogenic strains, the K-12 strain has a much smaller number of gene
      families, its gene families contain fewer genes, and gene conversions are less
      frequent. Whereas the three pathogenic strains have gene conversions covering
      hundreds of nucleotides when their flanking regions have as little as 50%
      similarity, flanking region similarity of at least 94% on both sides of the
      converted region is required to observe conversions of more than 87 nucleotides
      in the K-12 strain. Recombination is therefore more frequent and requires less
      sequence similarity in the three pathogenic strains than in K-12. This higher
      recombination level might be due to mutations in some of their mismatch-repair
      genes. In contrast with the gene conversions present in the yeast genome, the
      gene conversions found in the E. coli genomes do not occur more frequently
      between duplicated genes that are close to one another than between duplicated
      genes that are far apart and are randomly distributed along the length of the
      genes. In E. coli, gene conversions are not more frequent near the origin of
      replication. However, they do occur more frequently near the terminus of
      replication of the Sakai genome, where multigene family members are more
      abundant. This suggests that, in E. coli, gene conversions occur randomly between
      genes located in different chromosomal locations or located on different copies
      of the multiple chromosomes found in E. coli cells.

PMID- 15170260
TI  - Chinese strains (Type 7) of JC virus are afro-asiatic in origin but are
      phylogenetically distinct from the Mongolian and Indian strains (Type 2D) and the
      Korean and Japanese strains (Type 2A).
AB  - We have further characterized the Asian genotypes (Types 2 and 7) and subtypes of
      JC virus (JCV). Urine samples from 224 individuals with Han and Mongolian
      populations were collected in five regions in eastern China: Kunming, Chengdu,
      Shenyang, Chifeng, and Manzhouli. Also, 99 urine samples were collected from
      coastal and hill groups in Kerala, southern India, and 23 urine samples from
      Seoul, Korea. PCR products of four typing fragments were sequenced, including two
      in the VP1 gene, as well as one each in the VT intergenic region and regulatory
      region. It was possible to clone and sequence a total of 42 JCV whole genomes
      (approximately 5120 bp). Five genotypes of JCV (Types 7A, 7B, 7C, 2D, and 4) were
      found in China, four genotypes (Types 2D, 7C, 4, and 1B) in southern India, and
      three genotypes (Types 7B, 2A, and 1A) in Korea. Type 7A was most prevalent in
      South China (59-64%) and Type 7B was predominant in northeast China and Inner
      Mongolia (67-77%). Type 7C strains were spread throughout North and South China
      (3-14%), while Type 2D strains were found only in the two Mongolian groups (9
      10%). In southern India, Type 2D was predominant in the coastal group (95%), and
      two major types, Type 7C (50%) and Type 2D (35%), were prevalent in the tribal
      hill groups. In Korea two major genotypes were found: Type 7B (50%) and Type 2A
      (43%). Phylogenetic reconstruction places the Chinese genotypes in the Afro
      Asiatic supercluster, but distinct from the Mongolian and Indian strains (Type
      2D), as well as the Korean and Japanese genotype (Type 2A) that predominates in
      the Americas.

PMID- 15170268
TI  - Iatrogenic pathology: LASER ablation of vascular anastomoses in twin-twin
      transfusion syndrome.

PMID- 15170269
TI  - Randomized trial of different Intraabdominal pressures and acid-base balance
      alterations during laparoscopic cholecystectomy.

PMID- 15170264
TI  - Detection of lateral gene transfer events in the prokaryotic tRNA synthetases by
      the ratios of evolutionary distances method.
AB  - The availability of large numbers of genomic sequences has demonstrated the
      importance of lateral gene transfer (LGT) in prokaryotic evolution. However,
      considerable uncertainty remains concerning the frequency of LGT compared to
      other evolutionary processes. To examine LGTs in ancient lineages of prokaryotes
      a method was developed that utilizes the ratios of evolutionary distances (RED)
      to distinguish between alternative evolutionary histories. The advantages of this
      approach are that the variability inherent in comparing protein sequences is
      transparent, the direction of LGT and the relative rates of evolution are readily
      identified, and it is possible to detect other types of evolutionary events. This
      method was standardized using 35 genes encoding ribosomal proteins that were
      believed to share a vertical evolution. Using RED-T, an original computer program
      designed to implement the RED method, the evolution of the genes encoding the 20
      aminoacyl-tRNA synthetases was examined. Although LGTs were common in the
      evolution of the aminoacyl-tRNA synthetases, they were not sufficient to obscure
      the organismal phylogeny. Moreover, much of the apparent complexity of the gene
      tree was consistent with the formation of the paralogs in the ancestors to the
      modern lineages followed by more recent loss of one paralog or the other.

PMID- 15170271
TI  - Clinical caseload and surgical volume: a guide to quality?

PMID- 15170272
TI  - Marsupialization as a definitive treatment for the odontogenic keratocyst.
AB  - PURPOSE: We sought to show that marsupialization can be a definitive treatment
      for the odontogenic keratocyst (OKC). MATERIALS AND METHODS: Ten patients (10
      males and 4 females) between the ages of 11 and 64 with biopsy-proven OKC (8
      mandibular and 2 maxillary) measuring between 2 and 8 cm were treated by
      marsupialization consisting of excision of the overlying mucosa and the opening
      of a 1-cm window into the cystic cavity and, where possible, suturing of the cyst
      lining to the oral mucosa. Immunohistologic determination of bcl-2 was done for
      all samples of cyst lining. The cavities were kept open either by vigorous use of
      a home syringe by the patient or by suturing into place the flange and short
      length of a nasopharyngeal airway. Once the cyst had largely filled in,
      histologic material was taken from the base of the residual depression and
      studied by light microscopy and bcl-2 expression. RESULTS: In the 10 patients,
      the OKCs completely resolved both clinically and radiographically. The time taken
      for resolution varied from 7 to 19 months. In all cases, the histologic material
      obtained after marsupialization showed normal epithelium only, with no signs of
      cystic remnants, daughter cysts, or budding of the basal layer of the epithelium.
      At initial biopsy, bcl-2 was expressed in the keratocyst lining, but not in the
      histologic material obtained after marsupialization. Follow-up time ranged from a
      minimum of 1.8 years to a maximum of 4.8 years. Teeth at the periphery of the
      cysts were observed to upright and erupt. CONCLUSIONS: All 10 OKCs resolved
      completely after marsupialization. Teeth within the cyst were found to be upright
      and erupt. Marsupialization requires a cooperative patient who will irrigate the
      cavity and keep it open. It appears that the cyst lining is replaced by normal
      epithelium during this treatment.

PMID- 15170274
TI  - The ideal lavage volume for removing bradykinin, interleukin-6, and protein from
      the temporomandibular joint by arthrocentesis.
AB  - PURPOSE: The aim of this study was to investigate the ideal volume of perfusate
      for arthrocentesis of the temporomandibular joint (TMJ) disorders (TMDs).
      PATIENTS AND METHODS: We evaluated 17 joints in 17 patients with TMD in this
      study. Arthrocentesis of the TMJ was done by perfusion of 400 mL of Ringer's
      solution. The first 5 mL of perfusate was collected, and then a 5-mL sample was
      collected when the total volume of perfusate outflow approached 50, 100, 200,
      300, and 400 mL. The concentrations of bradykinin, interleukin-6, and protein
      were measured by immunoassay. RESULTS: The concentration of bradykinin,
      interleukin-6, and protein during arthrocentesis were effectively reduced by more
      than 200 mL of lavage (P <.05). With a perfusate volume of 300 to 400 mL, the
      protein and bradykinin were no longer detectable. CONCLUSIONS: Arthrocentesis is
      effective for washing out bradykinin, interleukin-6, and protein from the TMJ,
      and the ideal lavage volume of perfusate for arthrocentesis is between 300 and
      400 mL.

PMID- 15170275
TI  - Evaluation of hemorrhage depressors on blood loss during orthognathic surgery: a
      retrospective study.
AB  - PURPOSE: Correction of dentofacial deformities by orthognathic surgery may cause
      significant bleeding and therefore hypotensive anesthesia is often used to reduce
      the blood loss. The main objective of the present clinical study was to determine
      whether the addition of hemorrhage depressors to other medication during
      orthognathic surgery would further reduce the blood loss. PATIENTS AND METHODS:
      Thirty patients, consecutively operated on with standardized Le Fort I
      osteotomies in 1998 (n = 15, control group) and 1999 (n = 15, treatment group),
      were included in the study. Both groups received hypotension anesthesia during
      surgery and the treatment group received additional hemorrhage depressors;
      tranexamic acid and desmopressin. RESULTS: The mean blood loss was 740 +/- 410 mL
      (11.3 mL/kg) in the control group and 400 +/- 210 mL (5.7 mL/kg) in the treatment
      group. The results showed a statistically significant reduction of blood loss in
      the treatment group (P <.01). CONCLUSIONS: This study shows that blood loss
      during orthognathic surgery under hypotensive anesthesia can be significantly
      reduced when a combination of tranexamic acid and desmopressin is added.

PMID- 15170276
TI  - The inverted temporalis muscle flap for intraoral reconstruction: its rationale
      and the results of its application.
AB  - PURPOSE: The purpose of this article was to show the discrepancies among the
      different parts of the temporalis muscle flap (TMF), to introduce a new
      rotational arc for the TMF based on these findings, and to examine the outcomes
      associated with the use of this modified method. MATERIALS AND METHODS: Two
      models were established on 5 human skulls to mimic the situations with the usual
      dissection technique or the extended dissection technique for the TMF. The
      lengths of the anterior part, the middle part, and the posterior part of the flap
      were measured and analyzed for statistical significance. A new rotational arc for
      the TMF was introduced, in which the flap was inverted beneath the zygomatic
      arch, placing the temporalis fascia away from the oral side. Seventeen
      consecutive oral cancer cases treated with either the traditional method or the
      inverted method of flap transposition were reviewed and divided into 2 groups
      dictated by the rotational arcs of their flaps. The traditional TMF was used in
      11 cases and the inverted TMF was used in 6 cases. Clinical examination and
      imaging studies were used for assessment of outcome, and the results from the 2
      patient groups were compared. RESULTS: The middle and posterior parts of the
      temporalis muscle were significantly longer than the anterior part on the skull
      models. However, the middle and posterior parts did not differ greatly in length.
      The extended dissection technique increased the flap length except for the
      anterior part. Both flaps were successful in closing the defects in all cases and
      healed well. No muscle necrosis was observed. However, the patients receiving the
      traditional TMF developed noticeable cheek fullness in 4 instances, sialocele in
      3, significant reduction of range of mouth opening in 2, and distinct
      velopharyngeal insufficiency in 2, whereas only 1 case in which the inverted TMF
      was used developed cheek fullness. CONCLUSIONS: The middle or posterior part of
      the temporalis flap is preferred over the anterior part for covering distant
      defects because of its extra length. The inverted TMF is simple and safe to
      apply. It can extend farther in the posterior oral cavity and has fewer
      complications than the traditional TMF.

PMID- 15170277
TI  - Management of cerebrospinal fluid leak associated with craniomaxillofacial
      trauma.
AB  - PURPOSE: The management of persistent, post-traumatic cerebrospinal fluid (CSF)
      rhinorrhea and otorrhea remains a surgical challenge. Repair of CSF leaks has
      evolved from that of an intracranial approach to one that is primarily
      extracranial and endoscopic. The purpose of this retrospective analysis is to
      determine the incidence of persistent CSF rhinorrhea and otorrhea and assess the
      clinical outcomes of patients presenting to a level 1 trauma center with
      posttraumatic CSF leaks who were managed by both surgical and nonsurgical means.
      PATIENTS AND METHODS: The records of all patients with basilar skull fractures
      and/or severe facial trauma presenting to a major level 1 trauma center from 1991
      to 2001 were reviewed. Patients diagnosed with CSF otorrhea or rhinorrhea, who
      had not undergone an intracranial procedure, elevation of depressed skull
      fractures, or received a ventriculostomy, were identified and their demographics
      recorded. For purposes of statistical comparison, patients were divided into 2
      groups: "leak" and "no leak." All patients in the leak group were initially
      observed for a period of 7 to 10 days. Persistent CSF leaks were managed by CSF
      diversion via lumber drainage for 5 to 7 days. Extracranial repair was performed
      only if lumbar drainage failed to resolve the leak. RESULTS: Seven hundred thirty
      five patients were identified who met the criteria for inclusion in the study.
      Thirty-four patients (incidence, 4.6%) were identified with CSF leak presenting
      as otorrhea (n = 25 [75.8%]) or rhinorrhea (n = 9 [26.5%]), which was diagnosed
      by clinical, laboratory, or radiographic examination (average age, 28.2 years;
      age range, 2 to 80 years; 23 males and 11 females). All patients in this study
      experienced successful resolution of CSF otorrhea or rhinorrhea by using a
      variable combination of observation, CSF diversion, and extracranial repair.
      There were no complications or cases of meningitis. Twenty-eight patients (84.6%)
      experienced uncomplicated resolution of the leak without treatment in 2 to 10
      days. Persistent CSF leak, defined by drainage greater than 7 days after injury,
      was identified in 6 patients (incidence, 0.8%), all except 1 who underwent CSF
      diversion via a lumbar drain for a period of 5 to 10 days. Two of these patients
      were treated successfully; the remaining 4 patients required surgical procedures.
      CONCLUSIONS: Post-traumatic CSF leaks are uncommon and will usually resolve
      without surgical intervention. Successful management in refractory cases often
      involves a combination of observation, CSF diversion, and/or extracranial and
      intracranial procedures.

PMID- 15170278
TI  - Facial trauma: a recurrent disease? The potential role of disease prevention.
AB  - PURPOSE: The objectives of this investigation were to determine a profile of
      facial trauma patients presenting to the emergency department of University
      Hospital, University of Medicine and Dentistry of New Jersey, Newark, NJ, and to
      assess patient interest in violence or stress reduction programs. MATERIALS AND
      METHODS: A prospective study of the patients was conducted with the aid of a data
      collection form generated specifically for the purpose of this study. Data
      regarding patient age, race, gender, various aspects of social history,
      mechanism, and nature of injury were collected over a period of 1 year. In
      addition, all patients were asked to respond to 4 health promotion questions. All
      patients for whom the oral maxillofacial surgery service was consulted were
      included in the study. Descriptive statistical analysis of the data was used.
      RESULTS: A total of 92 patients were enrolled, of whom 80% were males. The mean
      age of patients enrolled was 30.5 years with the peak incidence of injury
      occurring in the 20- to 30-year-old age group (n = 30). The most frequent
      etiology was assault (75%), followed by motor vehicle accidents (18.5%). The most
      frequently occurring injury was mandible fracture (46.7%), followed by
      lacerations (42.4%). Within the study sample, 42.4% had previous injuries.
      Patients with facial injuries were 1.5 times more likely to have experienced
      previous interpersonal violence. This patient group also expressed an
      overwhelming willingness to change their behavior patterns (91.3%). CONCLUSIONS:
      The findings of this investigation indicated that most facial trauma patients are
      between the ages of 20 and 30 years and male. Assault is the most common
      etiologic agent resulting in facial trauma. Mandible fractures and lacerations
      are the most likely injuries in the facial trauma patient. Patients experiencing
      recurrent trauma due to assault are more responsive to violence reduction
      programs than those experiencing only 1 assault.

PMID- 15170279
TI  - The presurgical workup before third molar surgery: how much is enough?
AB  - PURPOSE: We sought to assess the indications for patient referral for computed
      tomography (CT) scan before third molar extraction. The influence of the data
      obtained from the CT scans on the surgical outcome and morbidity was also
      evaluated. PATIENTS AND METHODS: There were 189 patients in the study (120
      females and 69 males). Sixty-five patients were referred to receive CT and formed
      the study group. The remaining patients were included in the control group.
      RESULTS: There were no statistically significant differences between the groups
      with regard to demographic data and tooth and root angulations. Indications for
      tooth extraction such as pain, swelling, pericoronitis, caries, endodontic
      problems, pathology, and prosthetic considerations were similar. The proximity of
      the tooth root to the inferior alveolar canal was the only statistically
      significant difference between the 2 groups (P <.001). The treatment plan
      outcomes for extraction, surgical extraction, and follow-up were comparable. The
      surgeon changed the initial decision from "surgical extraction" to "follow-up" in
      only 1 case after CT scan. CONCLUSIONS: Within the limits of the present study,
      it can be concluded that the main reason for CT scan referral is the proximity of
      the third molar root to the inferior alveolar canal (<1 mm). The data obtained
      from the CT scan had minimal effect on the final surgical outcome. The routine
      use of CT scan in cases of third molar extractions cannot be recommended.

PMID- 15170280
TI  - Patterns of maxillofacial injuries related to interaction with horses.
AB  - PURPOSE: Studies of trauma patients have described patterns of injuries sustained
      from unfortunate encounters with large animals. However, the patterns of
      maxillofacial injuries have yet to be reported. The goal of this investigation
      was to describe and report on maxillofacial injuries that are associated with
      interaction with horses. PATIENTS AND METHODS: Charts were selected from the
      trauma registry by E-code at a level 1 trauma center in Portland, OR. A
      retrospective review was performed on charts collected from the previous 5 years
      (1998-2002). Data were collected according to patient, pattern of injuries, and
      mechanism of injury. RESULTS: The 62 patients who were identified consisted of 15
      males (24%) and 47 females (76%) and ranged in age from 1 to 83 years (average
      age, 32 years; most frequent age, 12 years). Most of the accidents occurred in
      the spring months and involved a horse known to the patient. The most common
      mechanism was falling from the horse. However, being kicked was correlated with a
      more serious injury (P =.048). The most frequent injury was abrasion/contusion
      (24 [39%]), second were lacerations (20 [32%]), and third were fractures (18
      [29%]). Fifty (81%) were not wearing helmets. Forty-six (74%) of the patients had
      other associated injuries. CONCLUSIONS: In patients with facial injuries related
      to horses, younger females were the most frequently involved. Facial injuries
      were often associated with other types of injuries. Nearly a third of the facial
      injuries sustained were fractures. The percentage of riders without a helmet was
      high. However, in our patient population, wearing a helmet does not seem to add
      any protection to the face, and almost all of the accidents involved a horse
      known to the patient. More education aimed at horse owners regarding the use of
      helmets, proper handling and riding skills, and supervising young riders is
      encouraged to prevent further injuries.

PMID- 15170281
TI  - Frequency of maxillofacial injuries in all-terrain vehicle collisions.
AB  - PURPOSE: We sought to evaluate the frequency and distribution of maxillofacial
      injuries associated with all-terrain vehicle (ATV) collisions and to compare this
      with patients involved in motorcycle accidents over the same 5-year period at the
      University of Alabama at Birmingham. Patients and methods The records of all
      patients involved in ATV collisions who were admitted to the University of
      Alabama at Birmingham Trauma Center from January 1998 to January 2003 were
      reviewed. Age, gender, mechanism of injury, length of stay, Glasgow Coma Scale
      (GCS) score, maxillofacial injuries, Injury Severity Score (ISS), and
      maxillofacial Abbreviated Injury Scale (AIS) score were the factors considered
      for the study. These variables were also analyzed for patients involved in
      motorcycle collisions who sustained maxillofacial trauma. RESULTS: There were a
      total of 72 ATV collisions; 23 patients (32%) sustained maxillofacial injuries.
      The mean age was 31, and there were 59 males (82%) and 13 females (18%). The most
      common mechanism of injury was an ATV rollover. The warmer seasons and weekend
      days had the highest frequency of ATV trauma. Of the 23 patients who sustained
      maxillofacial injuries, the average maxillofacial AIS score was 2. The length of
      stay and GCS score were 8 days and 12, respectively, compared to 5 days and 15 in
      the nonmaxillofacial injury group. The most common maxillofacial fracture seen
      was a zygomaticomaxillary complex fracture (n = 8), followed by mandibular
      fractures (n = 6), and orbital floor blowout fractures (n = 5). Eighty-three
      percent of patients with maxillofacial injuries required an operative
      intervention during their hospitalization. The distribution of maxillofacial
      fractures in the ATV group was similar to that of an equivalent motorcycle group,
      but the frequency for the ATV group was higher (32% versus 8%). The length of
      stay for the motorcycle group was 11 days versus 8 days for the ATV group. The
      GCS scores, maxillofacial AIS scores, and ISS were similar between the 2 groups
      (12, 2, and 18, respectively). In patients who sustained maxillofacial fractures,
      neurologic injuries were the most frequent concomitant injury in the ATV group,
      whereas orthopedic injuries occurred more often in the motorcycle group.
      CONCLUSIONS: Maxillofacial injuries are common findings in ATV collisions. ATV
      patients with maxillofacial fractures have more neurologic impairment at
      admission and longer hospitalizations than patients sustaining motorcycle
      injuries. There needs to be an increase in the public health effort to educate
      individuals about the dangers of ATVs and to provide proper safety guidelines
      before the purchase of a vehicle.

PMID- 15170282
TI  - Overexpression of Rac-1 small GTPase binding protein in oral squamous cell
      carcinoma.
AB  - PURPOSE: Oral squamous cell carcinoma (OSCC) is a fairly common malignancy in
      Taiwan and most countries of South Asia due to the popularity of areca quid use.
      In vitro studies have indicated that Rac proteins, a member of ras-related small
      GTPase protein family, can regulate cytoskeletal structures and activate
      signaling cascade and have the potential to transform cultured cells. However,
      Rac alteration during oral carcinogenesis in vivo has yet to be shown. The
      present study was conducted to investigate the importance of Rac-1 in oral
      tumorigenesis in vivo. PATIENTS AND METHODS: Expression level of Rac-1 protein
      and mRNA in OSCC together with noncancerous match tissue (NCMT) was explored
      using immunohistochemistry and reverse transcription-polymerase chain reaction
      analysis. RESULTS: The immunoreactivity of Rac-1 was shown in a significantly
      higher fraction of OSCC (74%) relative to the 48% in NCMT (P =.03). Eight of 14
      (57%) available tissue pairs also showed overexpression of Rac-1 mRNA in OSCC
      than that in NCMT. The Rac-1 immunoreactivity did not differ significantly in
      accord with clinicopathologic parameters including areca quid use. However, 3 of
      4 recurrent OSCC studied lacked the Rac-1 immunoreactivity. CONCLUSIONS: Our
      results presented novel findings: Rac-1 overexpression is a frequent occurrence
      in OSCC, highlighting the involvement of GTPase elements in the neoplastic growth
      of OSCC.

PMID- 15170283
TI  - The effect of high local concentrations of antibiotics on demineralized bone
      induction in rats.
AB  - PURPOSE: This study evaluated the effect of high local concentrations of
      antibiotics on bone repair induced by demineralized bone in rats. MATERIALS AND
      METHODS: Seventy-two 3-week-old rats, weighing 200 to 300 g, were used for the
      experiment. Rats were divided into 4 groups: control group (group 1), saline
      impregnation group (group 2), gentamicin-impregnation group (group 3), and
      tetracycline-impregnation group (group 4). The rats were killed at 3, 8, and 12
      weeks after surgery. Samples were stained with hematoxylin-eosin and subjected to
      the histomorphometric analyses. RESULTS: There were significant differences in
      new bone formation among groups at all time periods. Comparing differences
      between groups at each time point, significantly more new bone formation was
      present in group 2 than in group 1 at 3 weeks, more in group 2 than in group 1
      and more in group 2 than in group 4 at 8 weeks, and the most in group 2 among all
      groups at 12 weeks. In terms of the time period, significantly more new bone
      formation was observed at 8 weeks during the time period between 3 and 8 weeks,
      and at 12 weeks during the time period between 3 and 12 weeks. CONCLUSIONS: Our
      result suggests that the bone graft material is most effective when mixed with
      saline for the regeneration of osseous defects.

PMID- 15170284
TI  - Influence of antiplatelet substances on platelet-rich plasma.
AB  - PURPOSE: Platelets containing a number of growth factors (platelet-derived growth
      factor [PDGF], transforming growth factor-beta [TGF-beta], etc) can be obtained
      in high concentrations through centrifugal separation and are used in clinical
      applications as platelet-rich plasma (PRP). However, only a few studies have been
      conducted on the growth factors present in PRP. In this study, we focused on the
      concentrations of growth factors in PRP and clarified the influence of using
      antiplatelet substances in the process of platelet concentration to improve the
      concentration rate of growth factors in PRP. MATERIALS AND METHODS: We made
      platelet pellets from whole blood obtained from humans with or without some
      antiplatelet substances (prostaglandin E1, aspirin, apyrase). Platelet pellets
      were resuspended in phosphate-buffered saline as platelet resuspensions. We
      measured PDGF and TGF-beta1 concentrations in the samples. In measurements, we
      had the samples treated to release growth factors from platelets to measure
      accurate concentrations. RESULTS: PDGF and TGF-beta1 were concentrated to a mean
      of over 400% in the samples with antiplatelet substances as compared with the
      samples without antiplatelet substances. CONCLUSIONS: The antiplatelet substances
      were effective for efficiently concentrating growth factors in platelets.

PMID- 15170285
TI  - Resorbable mesh as a containment system in reconstruction of the atrophic
      mandible fracture.
AB  - PURPOSE: The purpose of this article is to introduce the use of a resorbable
      material (L-lactide, Co DL-lactide) to help contain the bone graft used during
      the reconstruction of the edentulous atrophic mandibular fracture. TECHNIQUE:
      After the mandibular fracture was reduced and fixated with a large reconstruction
      plate, the resorbable mesh was contoured with scissors and a hot water bath. The
      mesh was secured into position with 1.5-mm tacks to the inferior border or buccal
      cortical plate of the mandible. The material was then filled with particulate
      bone graft harvested from the medial aspect of the anterior iliac crest. RESULTS:
      Two patients had augmentation of the superior aspect of the mandible and one
      patient had augmentation of the inferior aspect of the mandible. All patients
      were augmented at least 10 to 12 millimeters. The mean follow-up was 25 months.
      All went on to heal to complete bony union. CONCLUSION: This material can be used
      as a containment system when bone grafting the edentulous atrophic mandible
      fracture.

PMID- 15170286
TI  - Tissue-engineered bone for maxillary sinus augmentation.
AB  - PURPOSE: Autologous, allogenic, and alloplastic materials for bony reconstruction
      in the craniomaxillofacial region have specific drawbacks stimulating the ongoing
      search for new materials. Cultivated skin and mucosa grafts are in clinical
      routine use in head and neck reconstruction but so far, to the best of our
      knowledge, no successful clinical application has been described of periosteum
      derived tissue-engineered bone for augmentation of the edentulous posterior
      maxilla. PATIENTS AND METHODS: In a clinical study, augmentation of the posterior
      maxilla was carried out using a bone matrix derived from mandibular periosteum
      cells on an Ethisorb (Ethicon, Norderstedt, Germany) fleece. In this report, we
      show the fabrication of the matrix, clinical application, and results in 27
      patients. RESULTS: In 18 patients, an excellent clinical, radiologic, and
      histologic result could be proved 3 months after augmentation. Histologically,
      the bone biopsy samples from these patients revealed mineralized trabecular bone
      with remnants of the biomaterial. An unsuccessful result was found in 8 cases
      with a more extended augmentation procedure. The clinical inspection 3 months
      after augmentation showed almost no formation of new bone. In contrast, a
      replacement resorption with connective tissue was found. This may be the result
      of failure of the initial supply of the cells embedded within large cell-polymer
      constructs with sufficient oxygen and nutrients to sustain their survival and
      proliferation and allow for the integration of the developing tissue within the
      surrounding tissue. CONCLUSION: Our achieved results suggest that periosteum
      derived osteoblasts on a suitable matrix can form lamellar bone within 3 months
      after transplantation and provide a reliable basis for simultaneous or secondary
      insertion of dental implants.

PMID- 15170287
TI  - Large preauricular swelling in a 75-year-old woman.

PMID- 15170288
TI  - The laryngeal mask airway for general anesthesia: the case for its use.

PMID- 15170289
TI  - The case against the laryngeal mask airway for anesthesia in oral and
      maxillofacial surgery.

PMID- 15170290
TI  - Squamous odontogenic tumor associated with an erupting maxillary canine: case
      report.

PMID- 15170291
TI  - Malignant mesenchymal tumor arising from cherubism: a case report.

PMID- 15170292
TI  - Bilateral palatal reconstruction using 2 pedicled buccal fat pads in rhinolalea
      aperta after extensive necrotizing tonsillitis: a case report.

PMID- 15170293
TI  - Tetracycline bone labeling in surgical management of chronic osteomyelitis: a
      case report.

PMID- 15170294
TI  - Clinical and imaging diagnoses of intramuscular hemangiomas: the wattle sign and
      case reports.

PMID- 15170295
TI  - Piezoelectric bone cutting in multipiece maxillary osteotomies.

PMID- 15170298
TI  - Statistical analysis of single-molecule junctions.

PMID- 15170299
TI  - Taking snapshots of photoexcited molecules in disordered media by using pulsed
      synchrotron X-rays.
AB  - Photoexcited molecules are quintessential reactants in photochemistry. Structures
      of these photoexcited molecules in disordered media in which a majority of
      photochemical reactions take place remained elusive for decades owing to a lack
      of suitable X-ray sources, despite their importance in understanding fundamental
      aspects in photochemistry. As new pulsed X-ray sources become available, short
      lived excited-state molecular structures in disordered media can now be captured
      by using laser-pulse pump, X-ray pulse-probe techniques of third-generation
      synchrotron sources with time resolutions of 30-100 ps, as demonstrated by
      examples in this review. These studies provide unprecedented information on
      structural origins of molecular properties in the excited states. By using other
      ultrafast X-ray facilities that will be completed in the near future, time
      resolution for the excited-state structure measurements should reach the
      femtosecond time scales, which will make "molecular movies" of bond breaking or
      formation, and vibrational relaxation, a reality.

PMID- 15170300
TI  - Putting tert-butyl cation in a bottle.

PMID- 15170301
TI  - An efficient and general method for the synthesis of alpha,omega-difunctional
      reduced polypropionates by Zr-catalyzed asymmetric carboalumination: synthesis of
      the scyphostatin side chain.

PMID- 15170302
TI  - A double ring-closing metathesis approach for the synthesis of beta-C
      trisaccharides.

PMID- 15170303
TI  - Ethylene epoxidation on Ag: identification of the crucial surface intermediate by
      experimental and theoretical investigation of its electronic structure.

PMID- 15170304
TI  - New clathrate hydrate structure: high-pressure tetrahydrofuran hydrate with one
      type of cavity.

PMID- 15170305
TI  - Synthesis of dendritic polyoxometalate complexes assembled by ionic bonding and
      their function as recoverable and reusable oxidation catalysts.

PMID- 15170306
TI  - Polysulfones: catalysts for alkene isomerization.

PMID- 15170307
TI  - A concise asymmetric synthesis of the marine hepatotoxin 7-epicylindrospermopsin.

PMID- 15170308
TI  - Luminescent 2D macrocyclic networks based on starburst molecules:
      [[Ag(CF(3)SO(3)](1.5)(tdapb)] and [[Ag(NO(3)](3)(tdapb)].

PMID- 15170309
TI  - A peptidomimetic HIV-entry inhibitor directed against the CD4 binding site of the
      viral glycoprotein gp120.

PMID- 15170311
TI  - Photoluminescence properties of discrete conjugated wires wrapped within
      dendrimeric envelopes: "dendrimer effects" on pi-electronic conjugation.

PMID- 15170310
TI  - A genetically encoded fluorescent reporter of histone phosphorylation in living
      cells.

PMID- 15170312
TI  - A new type of material for the recovery of hydrogen from gas mixtures.

PMID- 15170313
TI  - Doubly N-confused pentaphyrins.

PMID- 15170314
TI  - A carbon material as a strong protonic acid.

PMID- 15170315
TI  - The first account of a structurally persistent micelle.

PMID- 15170316
TI  - The glycosyltransferase UrdGT2 catalyzes both C- and O-glycosidic sugar
      transfers.

PMID- 15170317
TI  - A silicon analogue of vinyllithium: structural characterization of a disilenide.

PMID- 15170318
TI  - An efficient synthesis of diaryl ketones by iron-catalyzed arylation of aroyl
      cyanides.

PMID- 15170320
TI  - Structural principles for the multispecificity of small GTP-binding proteins.
AB  - The functional diversity of small GTP-binding proteins (G proteins) and their
      ability to function as molecular switches are based on their interactions with
      many different proteins. A wealth of structural data has revealed that their
      partners are often unrelated to each other in sequence and structure, but their
      binding sites are in general overlapping, notably at the so-called switch
      regions, whose conformation is sensitive to the nature of the bound nucleotide.
      We termed "multispecificity" this unique property of G proteins and investigated
      its structural principles by a database-implemented comparison of their protein
      protein interfaces. Multispecific residues were found to be distributed
      throughout the G protein surface, with the highest multiplicity at the switch
      regions, each engaging interactions with 50-80% of the bound partners.
      Remarkably, residues involved in multiple interactions do not define consensus
      binding sites where all partners have convergent interactions. Rather, they adapt
      to multiple stereochemical and structural environments by combining the composite
      nature of amino acids with structural plasticity. We propose that not only the
      nucleotide switch but also multispecificity is the hallmark of the G protein
      module. Thus, G proteins are representative of highly connected proteins located
      at nodes of protein interactomes, probably the best structurally characterized
      member of this emerging class of proteins to date. This central functional
      property is also their Achilles' heal, facilitating their hijacking by pathogens,
      but may constitute an unexplored advantage in designing or screening novel
      therapeutic molecules.

PMID- 15170321
TI  - DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding
      sites.
AB  - Four crystal structures of EcoRV endonuclease mutants K92A and K38A provide new
      insight into the mechanism of DNA bending and the structural basis for metal
      dependent phosphodiester bond cleavage. The removal of a key active site positive
      charge in the uncleaved K92A-DNA-M(2+) substrate complex results in binding of a
      sodium ion in the position of the amine nitrogen, suggesting a key role for a
      positive charge at this position in stabilizing the sharp DNA bend prior to
      cleavage. By contrast, two structures of K38A cocrystallized with DNA and Mn(2+)
      ions in different lattice environments reveal cleaved product complexes featuring
      a common, novel conformation of the scissile phosphate group as compared to all
      previous EcoRV structures. In these structures, the released 5'-phosphate and 3'
      OH groups remain in close juxtaposition with each other and with two Mn(2+) ions
      that bridge the conserved active site carboxylates. The scissile phosphates are
      found midway between their positions in the prereactive substrate and
      postreactive product complexes of the wild-type enzyme. Mn(2+) ions occupy two of
      the three sites previously described in the prereactive complexes and are
      plausibly positioned to generate the nucleophilic hydroxide ion, to compensate
      for the incipient additional negative charge in the transition state, and to
      ionize a second water for protonation of the 3'-oxyanion. Reconciliation of these
      findings with earlier X-ray and fluorescence studies suggests a novel mechanism
      in which a single initially bound metal ion in a third distinct site undergoes a
      shift in position together with movement of the scissile phosphate deeper into
      the active site cleft. This reconfigures the local environment to permit binding
      of the second metal ion followed by movement toward the pentacovalent transition
      state. The new mechanism suggested here embodies key features of previously
      proposed two- and three-metal catalytic models, and offers a view of the
      stereochemical pathway that integrates much of the copious structural and
      functional data that are available from exhaustive studies in many laboratories.

PMID- 15170322
TI  - Acid-base equilibria in rhodopsin: dependence of the protonation state of glu134
      on its environment.
AB  - Glutamic acid E134 in rhodopsin is part of a highly conserved triad, D(E)RY,
      located near the cytoplasmic lipid/water interface in transmembrane helix 3 of G
      protein-coupled receptors (GPCRs). A large body of experimental evidence suggests
      that the protonation of E134 plays a role in the mechanism of activation of
      rhodopsin and other GPCRs as well. For E134 to change its protonation state, its
      pK(a) value must shift from values below physiological pH to higher values.
      Because of the proximity of the triad to the lipid/water interface, it was
      hypothesized that a change in solvent around E134 from water to lipid could
      induce such a shift in pK(a). To test this hypothesis, the pK(a) values of the
      titratable amino acid residues in rhodopsin have been calculated and the change
      in solvent around E134 was modeled by shifting the position of the lipid/water
      interface. The approach used to carry out the pK(a) calculations takes into
      account the partial immersion of transmembrane proteins in lipid. Qualitative
      experimental evidence is available for several residues regarding their likely
      protonation state in rhodopsin at or near physiological pH. Comparison of the
      calculated pK(a) values with these experimental findings shows good agreement
      between the two. Notably, glutamic acids E122 and E181 were found to be
      protonated. The pK(a) values were then calculated for a range of lipid/water
      interface positions. Although the surrounding solvent of several titratable
      residues changed from water to lipid in this range, leading to pK(a) shifts in
      most cases, only for E134 would the shift lead to a change in protonation state
      at physiological pH. Thus, our results show that the protonation state of E134 is
      particularly sensitive to its environment. This sensitivity together with the
      location of E134 near the actual position of the lipid/water interface could be a
      strategic element in the mechanism of activation of rhodopsin.

PMID- 15170323
TI  - Serine hydroxymethyltransferase: role of glu75 and evidence that serine is
      cleaved by a retroaldol mechanism.
AB  - Serine hydroxymethyltransferase (SHMT) catalyzes the reversible interconversion
      of serine and glycine with tetrahydrofolate serving as the one-carbon carrier.
      SHMT also catalyzes the folate-independent retroaldol cleavage of allothreonine
      and 3-phenylserine and the irreversible conversion of 5,10
      methenyltetrahydrofolate to 5-formyltetrahydrofolate. Studies of wild-type and
      site mutants of SHMT have failed to clearly establish the mechanism of this
      enzyme. The cleavage of 3-hydroxy amino acids to glycine and an aldehyde occurs
      by a retroaldol mechanism. However, the folate-dependent cleavage of serine can
      be described by either the same retroaldol mechanism with formaldehyde as an
      enzyme-bound intermediate or by a nucleophilic displacement mechanism in which N5
      of tetrahydrofolate displaces the C3 hydroxyl of serine, forming a covalent
      intermediate. Glu75 of SHMT is clearly involved in the reaction mechanism; it is
      within hydrogen bonding distance of the hydroxyl group of serine and the formyl
      group of 5-formyltetrahydrofolate in complexes of these species with SHMT. This
      residue was changed to Leu and Gln, and the structures, kinetics, and spectral
      properties of the site mutants were determined. Neither mutation significantly
      changed the structure of SHMT, the spectral properties of its complexes, or the
      kinetics of the retroaldol cleavage of allothreonine and 3-phenylserine. However,
      both mutations blocked the folate-dependent serine-to-glycine reaction and the
      conversion of methenyltetrahydrofolate to 5-formyltetrahydrofolate. These results
      clearly indicate that interaction of Glu75 with folate is required for folate
      dependent reactions catalyzed by SHMT. Moreover, we can now propose a promising
      modification to the retroaldol mechanism for serine cleavage. As the first step,
      N5 of tetrahydrofolate makes a nucleophilic attack on C3 of serine, breaking the
      C2-C3 bond to form N5-hydroxymethylenetetrahydrofolate and an enzyme-bound
      glycine anion. The transient formation of formaldehyde as an intermediate is
      possible, but not required. This mechanism explains the greatly enhanced rate of
      serine cleavage in the presence of folate, and avoids some serious difficulties
      presented by the nucleophilic displacement mechanism involving breakage of the C3
      OH bond.

PMID- 15170324
TI  - Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and
      BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI
      selectivity.
AB  - The search for new cancer therapeutics has identified protein farnesyltransferase
      (FTase) as a promising drug target. This enzyme attaches isoprenoid lipids to
      signal transduction proteins involved in growth and differentiation. The two
      FTase inhibitors (FTIs), R115777 (tipifarnib/Zarnestra) and BMS-214662, have
      undergone evaluation as cancer therapeutics in phase I and II clinical trials.
      R115777 has been evaluated in phase III clinical trials and shows indications for
      the treatment of blood and breast malignancies. Here we present crystal
      structures of R115777 and BMS-214662 complexed with mammalian FTase. These
      structures illustrate the molecular mechanism of inhibition and selectivity
      toward FTase over the related enzyme, protein geranylgeranyltransferase type I
      (GGTase-I). These results, combined with previous biochemical and structural
      analyses, identify features of FTase that could be exploited to modulate
      inhibitor potency and specificity and should aid in the continued development of
      FTIs as therapeutics for the treatment of cancer and parasitic infections.

PMID- 15170325
TI  - The protein backbone makes important contributions to 4-oxalocrotonate
      tautomerase enzyme catalysis: understanding from theory and experiment.
AB  - The role of polypeptide backbone interactions in 4-oxalocrotonate tautomerase
      (4OT) catalysis has been investigated using a combination of site-directed
      mutagenesis experiments with unnatural amino acids and quantum
      mechanical/molecular mechanical (QM/MM) calculations of the 4OT reaction
      mechanism. Energy barriers for the wild-type enzyme (wt-4OT) and for a 4OT
      analogue containing a backbone amide to ester bond mutation between Ile-7 and Leu
      8 [(OL8)4OT] were determined by both theory and experiment. The amide to ester
      bond mutation in (OL8)4OT effectively deleted a putative hydrogen bonding
      interaction between the enzyme's polypeptide backbone and its substrate. Recent
      theoretical calculations for the 4OT reaction mechanism suggested that this
      hydrogen bonding interaction helps properly position the substrate in the active
      site [Cisneros, G. A., et al. (2003) J. Am. Chem. Soc. 125, 10384-10393]. Our
      experimental results for (OL8)4OT reveal that the energy barrier for the (OL8)4OT
      catalyzed reaction was increased 1.8 kcal/mol over that of the wild-type enzyme.
      This increase was in good agreement with the 1.0 kcal/mol increase obtained from
      QM/MM calculations for this analogue. Our theoretical calculations further
      suggest the hydrogen bond deletion in (OL8)4OT results in a rearrangement of the
      substrate in the active site. In this rearrangement, an ordered water molecule
      loses its ability to stabilize the transition state (TS), and Arg-61 gains the
      ability to stabilize the TS. The predicted role of Arg-61 in (OL8)4OT catalysis
      was confirmed in kinetic experiments with an analogue of (OL8)4OT containing an
      Arg to Ala mutation at position 61.

PMID- 15170326
TI  - Abeta(1-28) fragment of the amyloid peptide predominantly adopts a polyproline II
      conformation in an acidic solution.
AB  - To structurally characterize the nonaggregated state of the amyloid beta peptide,
      which assembles into the hallmark fibrils of Alzheimer disease, we investigated
      the conformation of the N-terminal extracellular peptide fragment Abeta(1-28) in
      D(2)O at acidic pD by utilizing combined FTIR and isotropic and anisotropic Raman
      spectra measured between 1550 and 1750 cm(-1). Peptide aggregation is avoided
      under the conditions chosen. The amide I' band was found to exhibit a significant
      noncoincidence effect in that the first moment of the anisotropic Raman and of
      the IR band profile appears red-shifted from that of the isotropic Raman
      scattering. A simulation based on a coupled oscillator model involving all 27
      amide I' modes of the peptide reveals that the peptide adopts a predominantly
      polyproline II conformation. Our results are inconsistent with the notion that
      the monomeric form of Abeta(1-28) is a totally disordered, random-coil structure.
      Generally, they underscore the notion that polyproline II is a characteristic
      motif of the unfolded state of proteins and peptides.

PMID- 15170327
TI  - Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta
      precursor protein processing.
AB  - Lithium is one of the most widely used mood-stabilizing agents for the treatment
      of bipolar disorder. Although the underlying mechanism(s) of this mood stabilizer
      remains controversial, recent evidence linking lithium to
      neurotrophic/neuroprotective effects (Choi and Sung (2000) 1475, 225-230; Davies
      et al. (2000) 351, 95-105) suggests novel benefits of this drug in addition to
      mood stabilization. Here, we report that both lithium as well as valproic acid
      (VPA) inhibit beta-amyloid peptide (Abeta) production in HEK293 cells stably
      transfected with Swedish amyloid precursor protein (APP)(751) and in the brains
      of the PDAPP (APP(V717F)) Alzheimer's disease transgenic mouse model at
      clinically relevant plasma concentrations. Both lithium and VPA are known to be
      glycogen synthase kinase-3 (GSK3) inhibitors. Our studies reveal that GSK3beta is
      a potential downstream kinase, which modulates APP processing because inhibition
      of GSK3 activity by either a dominant negative GSK3beta kinase-deficient
      construct or GSK3beta antisense oligonucleotide mimics lithium and VPA effects.
      Moreover, lithium treatment abolished GSK3beta-mediated Abeta increase in the
      brains of GSK3beta transgenics and reduced plaque burden in the brains of the
      PDAPP (APP(V717F)) transgenic mice.

PMID- 15170329
TI  - Mutagenesis of glutamine 290 in Escherichia coli and mitochondrial elongation
      factor Tu affects interactions with mitochondrial aminoacyl-tRNAs and GTPase
      activity.
AB  - Elongation factor Tu (EF-Tu) is responsible for the delivery of the aminoacyl
      tRNAs (aa-tRNA) to the ribosome during protein synthesis. The primary sequence of
      domain II of EF-Tu is highly conserved. However, several residues thought to be
      important for aa-tRNA binding in this domain are not conserved between the
      mammalian mitochondrial and bacterial factors. One of these residues is located
      at position 290 (Escherichia coli numbering). Residue 290 is Gln in most of the
      prokaryotic factors but is conserved as Leu (L338) in the mammalian mitochondrial
      factors. This residue is in a loop contacting the switch II region of domain I in
      the GTP-bound structure. It also helps to form the binding pocket for the 5' end
      of the aa-tRNA in the ternary complex. In the present work, Leu338 was mutated to
      Gln (L338Q) in EF-Tu(mt). The complementary mutation was created at the
      equivalent position in E. coli EF-Tu (Q290L). EF-Tu(mt) L338Q functions as
      effectively as wild-type EF-Tu(mt) in poly(U)-directed polymerization with both
      prokaryotic and mitochondrial substrates and in ternary complex formation assays
      with E. coli aa-tRNA. However, the L338Q mitochondrial variant has a reduced
      affinity for mitochondrial Phe-tRNA(Phe). E. coli EF-Tu Q290L is more active in
      poly(U)-directed polymerization with both mitochondrial and prokaryotic
      substrates and has a higher GTPase activity in both the absence and presence of
      ribosomes. Surprisingly, while E. coli EF-Tu Q290L is more active in
      polymerization with mitochondrial Phe-tRNA(Phe), this variant has low activity in
      the formation of a stable ternary complex with mitochondrial aa-tRNA.

PMID- 15170330
TI  - T antigen origin-binding domain of simian virus 40: determinants of specific DNA
      binding.
AB  - To better understand origin recognition and initiation of DNA replication, we
      have examined by NMR complexes formed between the origin-binding domain of SV40 T
      antigen (T-ag-obd), the initiator protein of the SV40 virus, and cognate and
      noncognate DNA oligomers. The results reveal two structural effects associated
      with "origin-specific" binding that are absent in nonspecific DNA binding. The
      first is the formation of a hydrogen bond (H-bond) involving His 203, a residue
      that genetic studies have previously identified as crucial to both specific and
      nonspecific DNA binding in full-length T antigen. In free T-ag-obd, the side
      chain of His 203 has a pK(a) value of approximately 5, titrating to the
      N(epsilon)(1)H tautomer at neutral pH (Sudmeier, J. L., et al. (1996) J. Magn.
      Reson., Ser. B 113, 236-247). In complexes with origin DNA, His 203 N(delta)(1)
      becomes protonated and remains nontitrating as the imidazolium cation at all pH
      values from 4 to 8. The H-bonded N(delta1)H resonates at 15.9 ppm, an unusually
      large N-H proton chemical shift, of a magnitude previously observed only in the
      catalytic triad of serine proteases at low pH. The formation of this H-bond
      requires the middle G/C base pair of the recognition pentanucleotide, GAGGC. The
      second structural effect is a selective distortion of the A/T base pair
      characterized by a large (0.6 ppm) upfield chemical-shift change of its Watson
      Crick proton, while nearby H-bonded protons remain relatively unaffected. The
      results indicate that T antigen, like many other DNA-binding proteins, may employ
      "catalytic" or "transition-state-like" interactions in binding its cognate DNA
      (Jen-Jacobson, L. (1997) Biopolymers 44, 153-180), which may be the solution to
      the well-known paradox between the relatively modest DNA-binding specificity
      exhibited by initiator proteins and the high specificity of initiation.

PMID- 15170328
TI  - The accessibility of cys-120 in CheA(S) is important for the binding of CheZ and
      enhancement of CheZ phosphatase activity.
AB  - The cheA gene of Escherichia coli encodes two proteins from in-frame tandem
      translation start sites. The long form of CheA (CheA(L)) is the histidine kinase
      responsible for phosphorylating the response regulator, CheY. The short form of
      CheA (CheA(S)) is identical in domain structure to CheA(L) except that it is
      missing the first 97 amino acids. Reduced CheA(S) bound to and enhanced the
      activity of the phosphatase of phospho-CheY, CheZ. Oxidized CheA(S) was unable to
      interact with CheZ. Oxidized CheA(S) formed covalent dimers, whereas CheA(L) did
      not. This property was believed to be the result of an intermolecular disulfide
      bond. The CheA proteins contain three cysteine residues, one of which likely lies
      within the CheZ binding region of CheA(S) and is exposed to solvent. We
      identified the CheZ binding domain of CheA(S) by testing the various fragments of
      CheA(S) that contain cysteine residues for CheZ binding activity in an ELISA
      based CheA(S)-CheZ binding assay. Fragments of CheA(S) lacking the truncated P1
      domain of CheA(S) ('P1) were unable to bind CheZ. We also found that a fusion of
      the first 42 amino acids of CheA(S) ('P1 domain) to GST bound CheZ and enhanced
      its activity. The interaction between the GST-CheA[98-139] fusion protein and
      CheZ was dependent on the accessibility of a cysteine residue (Cys-120) located
      in the 'P1 domain.

PMID- 15170331
TI  - Contributions of the RNA-binding and linker domains and RNA structure to the
      specificity and affinity of the nucleolin RBD12/NRE interaction.
AB  - Nucleolin is a multidomain phosphoprotein involved in ribosome biogenesis. In
      vitro selection and binding studies with pre-rRNA fragments have shown that the
      first two RNA-binding domains (RBDs) in nucleolin (RBD12) recognize the consensus
      sequence (U/G)CCCG(A/G) in the context of a stem-loop structure (nucleolin
      recognition element = NRE). Structural studies of nucleolin RBD12 in complex with
      an in vitro selected NRE (sNRE) and a natural pre-rRNA NRE (b2NRE) have revealed
      that sequence-specific binding of the consensus NRE is achieved in a similar
      manner in both complexes using residues in both RBDs as well as the linker
      connecting them. Using fluorescence anisotropy (FA) and nuclear magnetic
      resonance (NMR), we demonstrate the importance of the linker for NRE affinity by
      showing that only the individual RBDs with the linker attached retain the ability
      to specifically bind, albeit weakly, to sNRE and b2NRE. Binding of RBD1 and RBD2
      to the NREs in trans is not detected even when one of the RBDs has the linker
      attached, which suggests that the linker also contributes to the affinity by
      tethering the two RBDs. To determine if binding of nucleolin RBD12 to natural
      NREs is dependent on a specific RNA stem-loop structure, as was the case for the
      sNRE, we conducted FA and NMR binding assays with nucleolin RBD12 and a single
      stranded NRE. The results show that nucleolin RBD12 sequence-specifically binds a
      single-stranded NRE with an affinity similar to that for b2NRE, indicating that a
      stem-loop structure is not required for the nucleolin RBD12/pre-rRNA NRE
      interaction.

PMID- 15170332
TI  - Quantitative binding models for CYP2C9 based on benzbromarone analogues.
AB  - The cytochrome P450 (CYP) isoforms involved in xenobiotic metabolism are enzymes
      whose substrate selectivity remains difficult to predict due to wide specificity
      and dynamic protein-substrate interactions. To uncover the determinants of
      specificity for cytochrome CYP2C9, a novel library of benzbromarone (bzbr)
      inhibitors was used to reevaluate its pharmacophore. CoMSIA was used with the
      bzbr ligands to generate both quantitative binding models and three-dimensional
      contour plots that pinpoint predicted interactions that are important for binding
      to 2C9. Since this class of compounds is more potent than any other toward 2C9,
      the small molecule properties deemed most ideal by the software were used to
      address protein-ligand interactions using new mutagenesis and structural data.
      Nine new bzbr analogues provide evidence that specific electrostatic and
      hydrophobic interactions contribute the most to 2C9's specificity. Three of the
      new analogues are better isosteres of bzbr that contain bulky groups adjacent to
      the phenol and have increased pK(a) values. These ligands test the hypothesis
      that anionic substrates bind with higher affinity to 2C9. Since they have higher
      affinity than the previous nonacidic analogues, the importance of bulky groups on
      the phenol ring appears to have been underestimated. CoMSIA models predict that
      these bulky groups are favorable for their hydrophobicity, while a negative
      charge is favored at the ketone oxygen rather than the phenol oxygen. The overlap
      of this ketone with electronegative groups of other 2C9 substrates suggests they
      act as key positive charge acceptors.

PMID- 15170334
TI  - Foldability, enzymatic activity, and interacting ability of barnase mutants
      obtained by permutation of secondary structure units.
AB  - Barnase, a well-characterized ribonuclease, has been decomposed into six modules
      (M1-M6) or secondary structure units (S1-S6). We have studied the foldability and
      activity of the barnase mutants obtained by permutation of the four internal
      modules (M2-M5) or secondary structure units (S2-S5) to investigate whether
      permutation of these building blocks is a useful way to create foldable and/or
      functional proteins. In this study, we found that one of the secondary structure
      unit mutants was expressed in Escherichia coli only when His102 was substituted
      by alanine, which is a catalytic residue of wild-type barnase. This mutant
      (S2354H102A) had ordered conformations, which unfolded cooperatively during urea
      induced unfolding experiments. S2354H102A interacted with other barnase mutants
      to show a distinct RNase activity, although its own activity was quite weak. This
      interaction was specific, because S2354H102A interacted with only barnase mutants
      having His 102 and certain orders of the secondary structure units giving a
      distinct RNase activity. These results suggest that secondary structure units
      permuted in barnase mutants maintain their intrinsic "interacting ability" that
      is used for the folding of wild-type barnase, and the units can form certain
      conformations that complement those of the appropriate counterparts. Seven of 23
      secondary structure unit mutants and only 2 of 23 module mutants had RNase
      activity. On the basis of the results of analyses of foldability and RNase
      activity of the mutants performed in this and previous studies, we conclude that
      secondary structure units are more suitable than modules as building blocks to
      create novel foldable and/or functional proteins in the case of barnase.

PMID- 15170333
TI  - Single chain variable fragments against beta-amyloid (Abeta) can inhibit Abeta
      aggregation and prevent abeta-induced neurotoxicity.
AB  - Beta-amyloid (Abeta) is a major pathological determinant of Alzheimer's disease
      (AD). Both active and passive immunization studies have shown that antibodies
      against Abeta are effective in decreasing cerebral Abeta levels, reducing Abeta
      accumulation, and attenuating cognitive deficits in animal models of AD. However,
      the therapeutic potential of these antibodies in human AD patients is limited
      because of adverse inflammatory reactions and cerebral hemorrhaging associated
      with the treatments. Here we show that single chain variable fragments (scFv's)
      represent an attractive alternative to more conventional antibody-based
      therapeutics to reduce Abeta toxicity. The binding affinities and binding
      epitopes of two different scFv's to Abeta were characterized using a surface
      plasmon resonance (SPR) biosensor. An scFv binding the 17-28 region of Abeta
      effectively inhibited in vitro aggregation of Abeta as determined by thioflavin T
      (ThT) fluorescence staining and atomic force microscopy (AFM) analysis, while an
      scFv binding the carboxyl-terminal region of Abeta (residues 29-40) did not
      inhibit aggregation. The scFv to the 17-28 region when co-incubated with Abeta
      not only decreased aggregation but also eliminated any toxic effects of
      aggregated Abeta on the human neuroblastoma cell line, SH-SY5Y. The ability of
      scFv's to inhibit both aggregation and cytotoxicity of Abeta indicates that
      scFv's have potential therapeutic value for treating AD.

PMID- 15170335
TI  - Solution structure of a methionine-rich 2S albumin from sunflower seeds:
      relationship to its allergenic and emulsifying properties.
AB  - The three-dimensional structure in aqueous solution of SFA-8, a 2S albumin 103
      residue protein from seeds of sunflower (Helianthus anuus L.), has been
      determined by NMR methods. An almost complete (1)H resonance assignment was
      accomplished from analysis of two-dimensional (2D) COSY and 2D TOCSY spectra, and
      the structure was computed by using restrained molecular dynamics on the basis of
      1393 upper limit distance constraints derived from NOE cross-correlation
      intensities measured in 2D NOESY spectra. In contrast with most other 2S
      albumins, SFA-8 consists of a single polypeptide chain without any cleavage in
      the segment of residues 30-46. The computed structures exhibited an rmsd radius
      of 0.52 A for the backbone structural core (residues 11-30 and 46-101) and 1.01 A
      for the side chain heavy atoms. The resulting structure consists of five
      amphipathic helices arranged in a right-handed superhelix, a folding motif first
      observed in nonspecific lipid transfer (nsLTP) proteins, and common to other 2S
      albumins. In contrast to nsLTP proteins, neither SFA-8 nor RicC3 (a 2S albumin
      from castor bean) has an internal cavity that is able to host a lipid molecule,
      which results from an exchange in the pairing of disulfide bridges in the CXC
      segment. Both 2S albumins and nonspecific lipid transfer proteins belong to the
      prolamin superfamily, which includes a number of important food allergens.
      Differences in the extension and solvent exposition of the so-called
      "hypervariable loop" (which connects helices III and IV) in SFA-8 and RicC3 may
      be responsible for the different allergenic properties of the two proteins. SFA-8
      has been shown to form highly stable emulsions with oil/water mixtures. We
      propose that these properties may be determined partly by a hydrophobic patch at
      the surface of the protein which consists of five methionines that partially hide
      the Trp76 residue. The flexibility of the loop which contains Trp76 and the
      hydrophobicity of the whole environment may favor a conformational change, by
      which the Trp76 side chain may become inserted into the oil phase.

PMID- 15170337
TI  - Cysteine-scanning mutagenesis and thiol modification of the Rickettsia prowazekii
      ATP/ADP translocase: evidence that transmembrane regions I and II, but not III,
      are structural components of the aqueous translocation channel.
AB  - The contribution of transmembrane regions I, II, and III of the Rickettsia
      prowazekii ATP/ADP translocase to the structure of the putative water-filled ATP
      translocation channel was evaluated from the accessibility of hydrophilic, thiol
      reactive, methanethiosulfonate reagents to a library of 68 independent cysteine
      substitution mutants heterologously expressed in Escherichia coli. The MTS
      reagents used were MTSES (negatively charged) and MTSET and MTSEA (both
      positively charged). Mutants F036C, Y042C, and R046C (TM I), K066C and P072C (TM
      II), and F101C, F105C, F108C, Y113C, and P114C (TM III) had no assayable
      transport activity, indicating that cysteine substitution at these positions may
      not be tolerated. All three MTS reagents inhibit the transport of ATP in mutants
      of TM I (L039C, S043C, S047C, I048C) and TM II (S061C, S063C, T067C, I069C,
      V070C, A074C). Further, these residues appear to cluster along a single face of
      the transmembrane domain. Preexposure of MTS-reactive mutants S047C (TM I) and
      T067C (TM II) to high levels of ATP resulted in protection from MTS-mediated
      inhibition. This indicated that both TM I and TM II make major contributions to
      the structure of an aqueous ATP translocation pathway. Finally, on the basis of
      the lack of accessibility of charged MTS reagents to the thiol groups in mutants
      of TM III, it appears that TM III is not exposed to the ATP translocation
      channel. Cysteine substitution of residues constituting a highly conserved
      "phenylalanine face" in TM III resulted in ablation of ATP transport activity.
      Further, substituting these phenylalanine residues for either isoleucine or
      tyrosine also resulted in much lower transport activity, indicating that some
      property of phenylalanine at these positions that is not shared by cysteine,
      isoleucine, or tyrosine is critical to translocase activity.

PMID- 15170338
TI  - Interactions stabilizing the structure of the core light-harvesting complex (LH1)
      of photosynthetic bacteria and its subunit (B820).
AB  - Reconstitution experiments with a chemically synthesized core light-harvesting
      (LH1) beta-polypeptide analogue having 3-methylhistidine instead of histidine in
      the position that normally donates the coordinating ligand to bacteriochlorophyll
      (Bchl) have provided the experimental data needed to assign to B820 one of the
      two possible alphabeta.2Bchl pairs that are observed in the crystal structure of
      LH2 from Phaeospirillum (formerly Rhodospirillum) molischianum, the one with
      rings III and V of Bchl overlapping. Consistent with the assigned structure,
      experimental evidence is provided to show that significant stabilizing
      interactions for both the subunit complex (B820) and LH1 occur between the N
      terminal regions of the alpha- and beta-polypeptides. On the basis of the results
      with the chemically synthesized polypeptides used in this study, along with
      earlier results with protease-modified polypeptides, mutants, and chemically
      synthesized polypeptides, the importance of a stretch of 9-13 amino acids at the
      N-terminal end of the alpha- and beta-polypeptides is underscored. A progressive
      loss of interaction with the LH1 beta-polypeptide was found as the first three N
      terminal amino acids of the LH1 alpha-polypeptide were removed. The absence of
      the N-terminal formylmethionine (fMet), or conversion of the sulfur in this fMet
      to the sulfoxide, resulted in a decrease in LH1 formation. In addition to the
      removal of fMet, removal of the next two amino acids also resulted in a decrease
      in K(assoc) for B820 formation and nearly eliminated the ability to form LH1. It
      is suggested that the first three amino acids (fMetTrpArg) of the LH1 alpha
      polypeptide of Rhodospirillum rubrum form a cluster that is most likely involved
      in close interaction with the side chain of His -18 (see Figure 1 for numbering
      of amino acids) of the beta-polypeptide. The results provide evidence that the
      folding motif of the alpha- and beta-polypeptides in the N-terminal region
      observed in crystal structures of LH2 is also present in LH1 and contributes
      significantly to stabilizing the complex.

PMID- 15170336
TI  - Recognition of anionic phospholipid membranes by an antihemostatic protein from a
      blood-feeding insect.
AB  - The saliva of blood-feeding insects contains a variety of molecules having
      antihemostatic activity. Here, we describe nitrophorin 7 (NP7), a salivary
      protein that binds with high affinity to anionic phospholipid membranes. The
      protein is apparently targeted to the negatively charged surfaces of activated
      platelets and other cells, where it can serve as a vasodilator, antihistamine,
      platelet aggregation inhibitor, and anticoagulant. As with other members of the
      nitrophorin group, NP7 reversibly binds a molecule of NO and binds histamine with
      high affinity. The protein differs from other nitrophorins in that it binds to
      membranes containing phosphatidylserine. Sedimentation and surface plasmon
      resonance experiments, revealed two classes of phospholipid-binding sites having
      K(d) values of 4.8 and 755 nM. NP7 inhibits prothrombin activation by blocking
      phospholipid binding sites for the prothrombinase complex on the surfaces of
      vesicles and activated platelets. As a NO complex, NP7 inhibits collagen and ADP
      induced platelet aggregation and induces disaggregation of ADP-stimulated
      platelets by an NO-mediated mechanism. Molecular modeling of NP7 revealed a
      putative, positively charged membrane interaction surface comprised mainly of a
      helix lying outside of the lipocalin beta-barrel structure.

PMID- 15170340
TI  - Mutation and evolution of the magnesium-binding site of a class II aminoacyl-tRNA
      synthetase.
AB  - Aminoacyl-tRNA synthetases contain one or three Mg(2+) ions in their catalytic
      sites. In addition to their role in ATP binding, these ions are presumed to play
      a role in catalysis by increasing the electropositivity of the alpha-phosphate
      and stabilizing the pentavalent transition state. In the class II aaRS, two
      highly conserved carboxylate residues have been shown to participate with Mg(2+)
      ions in binding and coordination. It is shown here that these carboxylate
      residues are absolutely required for the activity of Saccharomyces cerevisiae
      aspartyl-tRNA synthetase. Mutants of these residues exhibit pleiotropic effects
      on the kinetic parameters suggesting an effect at an early stage of the
      aminoacylation reaction, such as the binding of ATP, Mg(2+), aspartic acid, or
      the amino acid activation. Despite genetic selections in an APS-knockout yeast
      strain, we were unable to select a single active mutant of these carboxylate
      residues. Nevertheless, we isolated an intragenic suppressor from a combinatorial
      library. The active mutant showed a second substitution close to the first one,
      and exhibited a significant increase of the tRNA aminoacylation rate. Structural
      analysis suggests that the acceptor stem of the tRNA might be repositioned to
      give a more productive enzyme:tRNA complex. Thus, the initial defect of the
      activation reaction was compensated by a significant increase of the
      aminoacylation rate that led to cellular complementation.

PMID- 15170341
TI  - Role of hydrogen bonding in the active site of human manganese superoxide
      dismutase.
AB  - The side chain of Gln143, a conserved residue in manganese superoxide dismutase
      (MnSOD), forms a hydrogen bond with the manganese-bound solvent and is critical
      in maintaining catalytic activity. The side chains of Tyr34 and Trp123 form
      hydrogen bonds with the carboxamide of Gln143. We have replaced Tyr34 and Trp123
      with Phe in single and double mutants of human MnSOD and measured their catalytic
      activity by stopped-flow spectrophotometry and pulse radiolysis. The replacements
      of these side chains inhibited steps in the catalysis as much as 50-fold; in
      addition, they altered the gating between catalysis and formation of a peroxide
      complex to yield a more product-inhibited enzyme. The replacement of both Tyr34
      and Trp123 in a double mutant showed that these two residues interact
      cooperatively in maintaining catalytic activity. The crystal structure of
      Y34F/W123F human MnSOD at 1.95 A resolution suggests that this effect is not
      related to a conformational change in the side chain of Gln143, which does not
      change orientation in Y34F/W123F, but rather to more subtle electronic effects
      due to the loss of hydrogen bonding to the carboxamide side chain of Gln143. Wild
      type MnSOD containing Trp123 and Tyr34 has approximately the same thermal
      stability compared with mutants containing Phe at these positions, suggesting the
      hydrogen bonds formed by these residues have functional rather than structural
      roles.

PMID- 15170339
TI  - Proximal and distal influences on ligand binding kinetics in microperoxidase and
      heme model compounds.
AB  - We use laser flash photolysis and time-resolved Raman spectroscopy of CO-bound
      heme complexes to study proximal and distal influences on ligand rebinding
      kinetics. We report kinetics of CO rebinding to microperoxidase (MP) and 2
      methylimidazole ligated Fe protoporphyrin IX in the 10 ns to 10 ms time window.
      We also report CO rebinding kinetics of MP in the 150 fs to 140 ps time window.
      For dilute, micelle-encapsulated (monodisperse) samples of MP, we do not observe
      the large amplitude geminate decay at approximately 100 ps previously reported in
      time-resolved IR measurements on highly concentrated samples [Lim, M., Jackson,
      T. A., and Anfinrud, P. A. (1997) J. Biol. Inorg. Chem. 2, 531-536]. However, for
      high concentration aggregated samples, we do observe the large amplitude
      picosecond CO geminate rebinding and find that it is correlated with the absence
      of the iron-histidine vibrational mode in the time-resolved Raman spectrum. On
      the basis of these results, the energetic significance of a putative distal
      pocket CO docking site proposed by Lim et al. may need to be reconsidered.
      Finally, when high concentration samples of native myoglobin (Mb) were studied as
      a control, an analogous increase in the geminate rebinding kinetics was not
      observed. This verifies that studies of Mb under dilute conditions are applicable
      to the more concentrated regime found in the cellular milieu.

PMID- 15170342
TI  - Toward better antibiotics: crystallographic studies of a novel class of DD
      peptidase/beta-lactamase inhibitors.
AB  - Beta-lactam antibiotics are vital weapons in the treatment of bacterial
      infections, but their future is under increasing threat from beta-lactamases.
      These bacterial enzymes hydrolyze and inactivate beta-lactam antibiotics,
      rendering the host cell resistant to the bactericidal effects of the drugs.
      Nevertheless, the bacterial D-alanyl-D-alanine transpeptidases (DD-peptidases),
      the killing targets of beta-lactams, remain attractive targets for antibiotic
      compounds. Cyclic acyl phosph(on)ates have been developed and investigated as
      potential inhibitors of both transpeptidases and beta-lactamases. The X-ray
      crystal structures of the complexes of the Streptomyces strain R61 DD-peptidase
      inhibited by a bicyclic [1-hydroxy-4,5-benzo-2,6-dioxaphosphorinanone(3)-1-oxide]
      and a monocyclic [1-hydroxy-4-phenyl-2,6-dioxaphosphorinanone(3)-1-oxide] acyl
      phosphate were determined to investigate the mode of action of these novel
      inhibitors. The structures show, first, that these inhibitors form covalent bonds
      with the active site serine residue of the enzyme and that the refractory
      complexes thus formed are phosphoryl-enzyme species rather than acyl enzymes. The
      complexes are long-lived largely because, after ring opening, the ligands adopt
      conformations that cannot directly recyclize, the latter a phenomenon previously
      observed with cyclic acyl phosph(on)ates. While the two inhibitors bind in nearly
      identical conformations, the phosphoryl-enzyme complex formed from the monocyclic
      compound is significantly less mobile than that formed from the bicyclic
      compound. Despite this difference, the complex with the bicyclic compound breaks
      down to regenerate free enzyme somewhat more slowly than that of the monocyclic.
      This may be because of steric problems associated with the reorientation of the
      larger bicyclic ligand required for reactivation. The structures are strikingly
      different in the orientation of the phosphoryl moiety from those generated using
      more specific phosph(on)ates. Models of the noncovalent complexes of the
      monocyclic compound with the R61 DD-peptidase and a structurally very similar
      class C beta-lactamase suggest reasons why the former enzyme is phosphorylated by
      this compound, while the latter is acylated. Finally, this paper provides
      information that will help in the design of additional DD-peptidase inhibitors
      with the potential to serve as leads in the development of novel antibiotics.

PMID- 15170343
TI  - pH Dependence of the reaction catalyzed by avian mitochondrial
      phosphoenolpyruvate carboxykinase.
AB  - The pH dependence of the reaction catalyzed by phosphoenolpyruvate carboxykinase
      (PEPCK) provides significant insight into the chemical mechanism. The pH
      dependence of k(cat) shows the importance of two acidic ionizations with pK(a)
      values of 6.5 and 7.0 assigned to the active site metal ligands H249 and K228. A
      single basic ionization is observed with an apparent pK(a) value of 8.4 that is
      assigned to K275 that is located in the P-loop motif and is essential for
      phosphoryl transfer. The pH dependence of k(cat)/K(M,PEP) demonstrates the
      importance of the same two acidic ionizations in the interaction of
      phosphoenolpyruvate with PEPCK and a single basic ionization with a pK(a) value
      of 8.1 that is assigned to Y220. The interaction of Mg-IDP with PEPCK is
      dependent upon a single acidic ionization attributed to K228 and two basic
      ionizations, both having an average pK(a) value of 8.1. One of the basic
      ionizations is attributed to the P-loop lysine (K275) and the other to C273.

PMID- 15170344
TI  - Sry-directed sex reversal in transgenic mice is robust with respect to enhanced
      DNA bending: comparison of human and murine HMG boxes.
AB  - The testis-determining factor SRY contains an HMG box DNA-bending domain. Human
      and murine factors (hSRY and mSRY, respectively) exhibit marked sequence
      divergence and are reported to differ markedly in DNA bending properties.
      Surprisingly, the combined application of time-resolved fluorescence resonance
      energy transfer (tr-FRET) and permutation gel electrophoresis demonstrates that
      the hSRY-DNA complex is more sharply bent than the murine complex and not less
      bent as previously reported. tr-FRET-based analyses of the distribution of end-to
      end distances in the bent DNA-protein complexes further suggest that a broader
      range of DNA bend angles is populated in the murine ensemble than in the human
      ensemble. The two domains and their respective DNA complexes nevertheless exhibit
      similar thermodynamic stabilities. (1)H NMR spectra indicate analogous
      intercalation of distinct "cantilever" side chains (isoleucine or methionine)
      with subtle differences in induced DNA structure. Interchange of cantilevers does
      not affect DNA bending. That transgenic expression of either human or murine Sry
      in XX mice can confer a male somatic phenotype suggests that SRY-directed
      transcriptional regulation is robust to enhanced DNA bending and to changes in
      the precision of DNA bending. We propose that male-specific gene regulation
      requires DNA bending above a critical threshold set by architectural requirements
      of enhanceosome assembly.

PMID- 15170345
TI  - Role of Asn-16 and Ser-19 in anthopleurin B binding. Implications for the
      electrostatic nature of Na(V) site 3.
AB  - Anthopleurin B (ApB) is a type 1 sea anemone toxin, which binds to voltage
      sensitive sodium channels (Na(V)'s), thereby delaying channel inactivation.
      Previous work from our laboratories has demonstrated that the structurally
      unconstrained region involving residues 8-17 of this polypeptide, designated the
      Arg-14 loop, is important for full toxin affinity (Seibert et al., (2003)
      Biochemistry 42, 14515). Within this region, important contributions are made by
      residues Arg-12 and Leu-18 (Gallagher and Blumenthal, (1994) J. Biol. Chem. 269,
      254; Dias-Kadambi et al., (1996) J. Biol. Chem. 271, 23828). Moreover,
      replacement of glycine residues found at positions 10 or 15 of the loop by
      alanine has been shown to have profound, isoform-selective effects on toxin
      binding kinetics (Seibert et al., (2003)Biochemistry 42, 14515). To thoroughly
      understand the importance of this entire region, the work described here
      investigates the contribution of ApB residues Asn-16, Thr-17, and Ser-19 to toxin
      affinity and isoform selectivity. Our results demonstrate that residues within
      and proximal to the C terminus of the Arg-14 loop are important modulators of ApB
      affinity for Na(V) channels, indicating that the loop and channel site 3 are
      likely in close contact. A comparison of the effects of multiple replacements at
      each position reveals that Asn-16 and Ser-19 are involved in binding, whereas Thr
      17 is not. The fact that anionic replacements for Asn-16 or Ser-19 are highly
      deleterious for toxin binding strongly suggests that site 3 contains either
      formal anionic residues or regions of high electron density, which could be
      formed by aromatic clusters. These data represent the first indication of the
      presence of such residues or regions within Na(V) site 3.

PMID- 15170346
TI  - Effect of the number of nucleic acid oligomer charges on the salt dependence of
      stability (DeltaG 37degrees) and melting temperature (Tm): NLPB analysis of
      experimental data.
AB  - For nucleic acid oligomers with variable chain lengths, the salt concentration
      ([salt]) dependences of the denaturation temperature (T(m)) and of the free
      energy of helix formation at 37 degrees C (Delta) are predicted using nonlinear
      Poisson-Boltzmann (NLPB) calculations. Analysis of experimental data reveals that
      the ratio of the [salt] derivative of melting temperature (ST(m) = dT(m)/d
      log[salt]) to the value for a polymer with the same base composition (ST(m)/ST(m,
      infinity)) is independent of base composition but strongly dependent on the
      number of DNA charges (/Z/) below approximately 8 bp for two-strand helices
      (formed from association of two complementary strands) and below approximately 18
      bp for hairpin helices (formed from folding of one self-complementary strand). We
      interpret these ST(m)/ST(m, infinity) ratios in terms of the ratio of
      thermodynamic ion release from the oligomer (Deltan(u), per charge) to that from
      the same oligomer embedded in polymeric DNA (Deltan(u, infinity), per charge).
      Experimental values of ST(m)/ST(m, infinity) and its dependence on /Z/ are in
      good agreement with NLPB predictions for a preaveraged (essential structural)
      model of DNA. In particular, the NLPB calculations describe the stronger /Z/
      dependence of ST(m) observed for melting of oligomeric hairpin helices than for
      melting of two-strand helices. These calculations predict an experimentally
      detectable (>or=10%) difference between ST(m) and ST(m, infinity) which increases
      strongly with decreasing length for two-strand helix lengths of <15 bp and for
      hairpin helix lengths of <30 bp. From NLPB values of Deltan(u)/Deltan(u,
      infinity), we predict Delta as a function of [salt] and /Z/. Predictions of
      thermodynamic and thermal stabilities of oligomeric helices as functions of
      length and [salt] are consistent with and represent a significant refinement of
      the average oligomer salt effect currently in use in nearest neighbor stability
      predictions.

PMID- 15170347
TI  - Lipid modulation of protein-induced membrane domains as a mechanism for
      controlling signal transduction.
AB  - The reason for the enormous lipid variety present in eukaryotic membranes remains
      largely an enigma. We suggest that its role is to provide an on-off switch for a
      signaling event at the membrane level. This is achieved through lipid-lipid
      interactions that convert membrane protein binding and association events into
      very cooperative processes while maintaining reversibility. We have previously
      shown [Hinderliter, A., at al. (2001) Biochemistry 40, 4181-4191] that
      thermodynamic linkage between an intrinsic tendency for lipid demixing and a
      preferential interaction of a protein with a specific lipid within the mixture
      leads to dramatic changes in lipid and protein domain formation. Here, we tested
      the hypothesis that small alterations in lipid chemical structure alter the
      magnitude of the net interaction free energy (omega(AB)) between unlike lipids in
      a predictable manner, and that even very small changes in omega(AB) lead to
      dramatic changes in bilayer organization when coupled with protein binding. We
      systematically varied the chemical structure of phosphatidylcholine (PC), in
      mixtures with a fixed phosphatidylserine (PS), by changing the PC acyl chain
      length and the degree of unsaturation, and examined domain formation upon
      addition of a peripheral protein, the synaptotagmin I C2A motif. Experimental
      excimer/monomer ratios (E/M) of pyrene-substituted lipids mimicking the PS were
      interpreted using Monte Carlo computer simulations. E/M is larger if the PC
      melting temperature is lower, suggesting that domain formation is a thermodynamic
      consequence of weak interactions between PC and PS. Consistent with our
      hypothesis, only very small changes in omega(AB) were required for prediction of
      large changes in lipid and protein domain formation.

PMID- 15170348
TI  - An encephalitozoon cuniculi ortholog of the RNA polymerase II carboxyl-terminal
      domain (CTD) serine phosphatase Fcp1.
AB  - Fcp1 is an essential protein serine phosphatase that dephosphorylates Ser2 or
      Ser5 of the RNA polymerase II carboxyl-terminal domain (CTD) heptad repeat
      Y(1)S(2)P(3)T(4)S(5)P(6)S(7). The CTD of the microsporidian parasite
      Encephalitozoon cuniculi consists of 15 heptad repeats, which approximates the
      minimal CTD length requirement for cell viability in yeast. Here we show that E.
      cuniculi encodes a minimized 411-aa Fcp1-like protein (EcFcp1), which consists of
      a DxDx(T/V) phosphatase domain and a BRCA1 carboxyl terminus (BRCT) domain but
      lacks the large N- and C-terminal domains found in fungal and metazoan Fcp1
      enzymes. Nonetheless, EcFcp1 can function in lieu of Saccharomyces cerevisiae
      Fcp1 to sustain yeast cell growth. Recombinant EcFcp1 is a monomeric enzyme with
      intrinsic phosphatase activity against nonspecific (p-nitrophenyl phosphate) and
      specific (CTD-PO(4)) substrates. EcFcp1 dephosphorylates CTD positions Ser2 and
      Ser5 with similar efficacy in vitro. We exploit synthetic CTD Ser2-PO(4) and Ser5
      PO(4) peptides to define minimized substrates for EcFcp1 and to illuminate the
      importance of CTD primary structure in Ser2 and Ser5 phosphatase activity.

PMID- 15170349
TI  - Interaction of two prolamins with 1-13C oleic acid by 13C NMR.
AB  - In this paper, we analyzed the interaction of Z19 prolamin from a BR451 maize
      variety and pennisetin from a BRS1501 pearl millet variety with 1-(13)C-enriched
      oleic acid (OA) by (13)C NMR in solution. In both proteins, we identified the
      presence of free fatty acids by NMR in solid state and solution. The interactions
      were analyzed at the protein/OA molar ratios of 1:1 and 1:4. In the Z19/OA 1:1
      mixture in 70% ethanol and 30% D(2)O, the chemical shift of OA C1 was 182.9 ppm,
      about 3 ppm above that of the pure OA in the same solvent. In contrast, upon
      addition of OA to the pennisetin (1:1), the chemical-shift value slightly
      decreased by less than 1 ppm. The chemical-shift titration curve of OA C1 in an
      apparent pH range of 5.5-7.3 shifted by approximately 0.3 pH units toward higher
      pH values in the pennisetin/OA 1:1 complex relative to the pure OA. The results
      obtained for the pennisetin/OA 1:4 mixture were similar to the complexes at a 1:1
      molar ratio. A significant difference was observed between the 1:1 and 1:4 curves
      for Z19. The titration curve for Z19/OA 1:1 suggested specific binding at the
      sites with electrostatic interaction.

PMID- 15170350
TI  - In vitro activity differences between proteins of the ADF/cofilin family define
      two distinct subgroups.
AB  - The actin depolymerizing factor (ADF)/cofilins are an essential group of proteins
      that are important regulators of actin filament turnover in vivo. Although
      protists and yeasts express only a single member of this family, metazoans
      express two or more members in many cell types. In cells expressing both ADF and
      cofilin, differences have been reported in the regulation of their expression,
      their pH sensitivity, and their intracellular distribution. Each member has
      qualitatively similar interactions with actin, but quantitative differences have
      been noted. Here we compared quantitative differences between chick ADF and chick
      cofilin using several assays that measure G-actin binding, actin filament length
      distribution, and assembly/disassembly dynamics. Quantitative differences were
      measured in the critical concentrations of the complexes required for assembly,
      in the effects of nucleotide and divalent metal on actin monomer binding, in pH
      dependent severing, in enhancement of filament minus end off-rates, and in steady
      state filament length distributions generated in similar mixtures. Some of these
      assays were used to compare the activities of several ADF/cofilins from across
      phylogeny, most of which fall into one of two groups based upon their behavior.
      The ADF-like group has higher affinities for Mg(2+)-ATP-G-actin than the cofilin
      like group and a greater pH-dependent depolymerizing activity.

PMID- 15170351
TI  - Thermodynamic parameters based on a nearest-neighbor model for DNA sequences with
      a single-bulge loop.
AB  - All 64 possible thermodynamic parameters for a single-bulge loop in the middle of
      a sequence were derived from optical melting studies. The relative stability of a
      single bulge depended on both the type of bulged base and its flanking base
      pairs. The contribution of the single bulge to helix stability ranged from 3.69
      kcal/mol for a TAT bulge to -1.05 kcal/mol for an ACC bulge. Thermodynamics for
      10 sequences with a GTG bulge were determined to test the applicability of the
      nearest-neighbor model to a single-bulge loop. Thermodynamic parameters for the
      GTG bulge and Watson-Crick base pairs predict, DeltaH degrees, DeltaS degrees,
      and T(M)(50 microM) values with average deviations of 3.0%, 4.3%, 4.7%, and 0.9
      degrees C, respectively. The prediction accuracy was within the limits of what
      can be expected for a nearest-neighbor model. This certified that the
      thermodynamics for single-bulge loops can be estimated adequately using a nearest
      neighbor model.

PMID- 15170352
TI  - Higher metal-ligand coordination in the catalytic site of cobalt-substituted
      Thermoanaerobacter brockii alcohol dehydrogenase lowers the barrier for enzyme
      catalysis.
AB  - Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) is a zinc-dependent
      NADP(+)/H-linked class enzyme that reversibly catalyzes the oxidation of
      secondary alcohols to their corresponding ketones. Cobalt substitution studies of
      other members of the alcohol dehydrogenase (ADH) family showed that the cobalt
      containing ADHs have a similar active site structure but slightly decreased
      activity compared to wild-type zinc ADHs. In contrast, the cobalt-substituted
      TbADH (Co-TbADH) exhibits an increase in specific activity compared to the native
      enzyme [Bogin, O., Peretz, M., and Burstein, Y. (1997) Protein Sci. 6, 450-458].
      However, the structural basis underlying this behavior is not yet clear. To shed
      more light on this issue, we studied the local structure and electronics at the
      catalytic metal site in Co-TbADH by combining X-ray absorption (XAS) and quantum
      chemical calculations. Importantly, we show that the first metal-ligand
      coordination shell of Co-TbADH is distorted compared to its native tetrahedral
      coordination shell and forms an octahedral structure. This is mediated presumably
      by the addition of two water molecules and results in more positively charged
      catalytic metal ions. Recently, we have shown that the metal-ligand coordination
      number of the zinc ion in TbADH changes dynamically during substrate turnover.
      These structural changes are associated with a higher coordination number of the
      native catalytic zinc ion and the consequent buildup of a positive charge. Here
      we propose that the accumulation of a higher coordination number and positive
      charge at the catalytic metal ion in TbADH stabilizes the structure of the
      catalytic transition state and hence lowers the barrier for enzyme catalysis.

PMID- 15170353
TI  - High pressure induces scrapie-like prion protein misfolding and amyloid fibril
      formation.
AB  - Our understanding of conformational conversion of proteins in diseases is
      essential for any diagnostic and therapeutic approach. Although not fully
      understood, misfolding of the prion protein (PrP) is implicated in the
      pathogenesis of prion diseases. Despite several efforts to produce the
      pathologically misfolded conformation in vitro from a recombinant PrP, no
      positive result has yet been obtained. Within the "protein-only hypothesis", the
      reason for this hindrance may be that the experimental conditions used did not
      allow selection of the pathway adopted in vivo resulting in conversion into the
      infectious form. Here, using a pressure perturbation approach, we show that
      recombinant PrP is converted to a novel misfolded conformer, which is prone to
      aggregate and ultimately form amyloid fibrils. A short incubation at high
      pressure (600 MPa) of the truncated form of hamster prion protein (SHaPrP(90
      231)) resulted in the formation of pre-amyloid structures. The mostly globular
      aggregates were characterized by ThT and ANS binding, and by a beta-sheet-rich
      secondary structure. After overnight incubation at 600 MPa, amyloid fibrils were
      formed. In contrast to pre-amyloid structures, they showed birefringency of
      polarized light after Congo red staining and a strongly decreased ANS binding
      capacity, but enhanced ThT binding. Both aggregate types were resistant to
      digestion by PK, and can be considered as potential scrapie-like forms or
      precursors. These results may be useful for the search for compounds preventing
      pathogenic PrP misfolding and aggregation.

PMID- 15170354
TI  - Active site residues in Mycobacterium tuberculosis pantothenate synthetase
      required in the formation and stabilization of the adenylate intermediate.
AB  - Pantothenate synthetase (EC 6.3.2.1) catalyzes the formation of pantothenate from
      ATP, D-pantoate, and beta-alanine in bacteria, yeast, and plants. The three
      dimensional structural determination of pantothenate synthetase from
      Mycobacterium tuberculosis has indicated specific roles for His44, His47, Asn69,
      Gln72, Lys160, and Gln164 residues in the binding of substrates and the pantoyl
      adenylate intermediate. To evaluate the functional roles of these strictly
      conserved residues, we constructed six Ala mutants and determined their catalytic
      properties. The substitution of alanine for H44, H47, N69, Q72, and K160 residues
      in M. tuberculosis pantothenate synthetase caused a greater than 1000-fold
      reduction in enzyme activity, while the Q164A mutant exhibited 50-fold less
      activity. The rate of the isolated adenylation reaction in single turnover
      studies was also reduced 40-1000-fold by the replacement of one of these six
      amino acids with alanine, suggesting that these residues are essential for the
      formation of the pantoyl adenylate intermediate. The rate of pantothenate
      formation from the adenylate and beta-alanine in the second half reaction could
      not be measured for the H44A, H47A, N69A, Q72A, and K160A mutants and was reduced
      40-fold in the Q164A mutants. The activity of the K160C mutant enzyme was
      markedly enhanced by the alkylation of cysteine with bromoethylamine, further
      supporting the critical role of the K160 residue in pantoyl adenylate formation.
      Isothermal titration microcalorimetry analysis demonstrated that the substitution
      of either H47 or K160 for Ala resulted in a decreased affinity of the enzyme for
      ATP. These results indicate that the highly conserved His44, His47, Asn69, Gln72,
      Lys160 and residues are essential for the formation and stabilization of pantoyl
      adenylate intermediate in the pantothenate synthetase reaction.

PMID- 15170355
TI  - Receptor-ligand binding in the cell-substrate contact zone: a quantitative
      analysis using CX3CR1 and CXCR1 chemokine receptors.
AB  - Receptor-ligand binding analyses have generally used soluble components to
      measure thermodynamic binding constants. In their biological context, adhesion
      receptors bind to an immobile ligand and the binding reaction is confined to the
      cell-substrate contact zone. We have developed a new procedure based on the
      spinning disk technology to measure the number of receptor-ligand bonds in the
      contact zone. Application of this methodology to the CX3CR1-fractalkine and the
      CXCR1-IL-8 receptor-ligand systems demonstrated that the level of binding to an
      immobilized ligand is reduced by several orders of magnitude in comparison to
      solution binding. A comparison of the solution binding and contact zone binding
      constants shows that the effect of ligand immobilization was similar for each
      system. In contrast, although the CXCR1-IL-8 bond had the higher affinity, the
      average bond strength was only 10% of that for the CX3CR1 bond. Because
      fractalkine can be expressed as a cell surface-bound protein, CX3CR1 has been
      proposed to function as an adhesion receptor. The higher bond strength suggests
      that the bond architecture has also evolved to serve an adhesion function.

PMID- 15170356
TI  - Stereospecific alkylation of cis-3-chloroacrylic acid dehalogenase by (R)-oxirane
      2-carboxylate: analysis and mechanistic implications.
AB  - The enzymes trans-3-chloroacrylic acid dehalogenase (CaaD) and cis-3
      chloroacrylic acid dehalogenase (cis-CaaD) represent the two major classes of
      bacterial, isomer-selective 3-chloroacrylic acid dehalogenases. They catalyze the
      hydrolytic dehalogenation of either trans- or cis-3-haloacrylates to yield
      malonate semialdehyde, presumably through unstable halohydrin intermediates. In
      view of a proposed general acid/base mechanism for these enzymes, (R)- and (S)
      oxirane-2-carboxylate were investigated as potential irreversible inhibitors.
      Only cis-CaaD is irreversibly inhibited in a time- and concentration-dependent
      manner and only by the (R)-enantiomer of oxirane-2-carboxylate. The enzyme
      displays saturation kinetics and is protected from inactivation by the presence
      of substrate. These findings indicate that the inactivation process involves the
      initial formation of a reversibly bound enzyme-inhibitor complex at the active
      site followed by covalent modification. Mass spectral analysis of the inactivated
      cis-CaaD shows that Pro-1 is the site of modification. It has also been
      determined that Arg-70 and Arg-73 are required for covalent modification because
      incubation of either the R70A or R73A mutant with inhibitor does not result in
      enzyme alkylation. Studies of the pH dependence of the kinetic parameters of wild
      type cis-CaaD reveal that a protonated group with a pK(a) of approximately 9.3 is
      essential for catalysis. The group is likely Pro-1, making it predominately a
      charged species under the conditions of the inactivation experiments. Two
      mechanisms could account for these observations. In one mechanism, the oxirane
      undergoes acid-catalyzed ring opening followed by alkylation of the conjugate
      base of Pro-1. Alternatively, the oxirane undergoes a nucleophilic substitution
      reaction where the conjugate base of Pro-1 functions as the nucleophile and an
      acid catalyst polarizes the carbon oxygen bond. The two arginine residues likely
      bind the carboxylate group and position the inhibitor in a favorable orientation
      for the alkylation reaction. These findings set the stage for a crystallographic
      analysis of the inactived enzyme to delineate further the roles of active site
      residues in both the inactivation process and the catalytic mechanism.

PMID- 15170357
TI  - Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in
      human A673 neuroepithelioma cells results in a decrease in the level of bioactive
      NO production: analysis of the signaling mechanisms that are involved.
AB  - The expression level of neuronal nitric oxide synthase (nNOS) can vary depending
      on the (patho)physiological conditions. Here we document a marked induction of
      nNOS mRNA, protein, and total NO production in response to dibutyryl cyclic AMP
      (db-cAMP) in human A673 neuroepithelial cells. However, the upregulation of nNOS
      was associated with a decreased level of production of bioactive NO and by an
      increase in the level of generation of reactive oxygen species (ROS). ROS
      production could be prevented by the NOS inhibitor L-NAME, suggesting nNOS itself
      is involved in ROS generation. Sepiapterin supplementation of db-cAMP-treated
      A673 cells could restore full bioactive NO production, most likely by preventing
      the uncoupling of nNOS. nNOS was upregulated by other stable analogues of cAMP,
      by the activator of adenylyl cyclase forskolin, by isoproterenol or by dopamine
      through activation of D1 receptors, and by inhibitors of phosphodiesterase. cAMP
      did not change the half-life of the nNOS mRNA. Inhibitors of protein kinase A
      (PKA), H-89 and R(p)-cAMPS, produced a partial inhibition of basal and cAMP
      induced nNOS expression. cAMP response element binding and modulator
      transcription factors (CREB and CREM), typical target proteins of PKA, were
      expressed in A673 cells, as was the coactivator CREB binding protein (CBP). cAMP
      stimulated induction of nNOS was significantly enhanced in A673 cells stably
      transfected with wild-type CREB and almost abolished in cells transfected with
      KCREB (containing a mutation of the DNA binding domain). In A673 cells
      transfected with CREB(133) (containing a mutation of the phosphorylatable serine
      133), the overall level of nNOS expression was reduced, but the expressional
      stimulation by cAMP remained. This suggests that CREB bypasses, in part, the
      classical requirement for phosphorylation and association with CBP. Three members
      of the recently described four-and-a-half-LIM-domain proteins (FHL1-FHL3) were
      found to be expressed in A673 cells; FHL-1 and FHL-3 were upregulated by cAMP.
      These proteins can provide direct activation function to both CREB and CREM, and
      may be responsible for the PKA-independent component of CREB and CREM activity.

PMID- 15170359
TI  - High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated
      DNA loops.
AB  - We have recently observed that chromatin architectural protein HMGB1 (previously
      reported to be involved in numerous biological processes such as DNA replication,
      recombination, repair, tumor growth, and metastasis) could bind with extremely
      high affinity (K(d) < 1 pM) to a novel DNA structure that forms a DNA loop
      maintained at its base by a hemicatenane (hcDNA). The loop of hcDNA contains a
      track of repetitive sequences derived from CA-microsatellites. Here, we report
      using a gel-retardation assay that tumor-suppressor protein p53 can also bind to
      hcDNA. p53 is a crucial molecule protecting cells from malignant transformation
      by regulating cell-cycle progression, apoptosis, and DNA repair by activation or
      repression of transcription of its target genes by binding to specific p53 DNA
      binding sites and/or certain types of DNA lesions or alternative DNA structures.
      The affinity of p53 for hcDNA (containing sequences with no resemblance to the
      p53 DNA consensus sequence) is >40-fold higher (K(d) approximately 0.5 nM) than
      that for its natural specific binding sites within its target genes (Mdm2
      promoter). Binding of p53 to hcDNA remains detectable in the presence of up to
      approximately 4 orders of magnitude of mass excess of competitor linear DNA,
      suggesting a high specificity of the interaction. p53 displays a higher affinity
      for hcDNA than for DNA minicircles (lacking functional p53-specific binding
      sequence) with a size similar to that of the loop within the hcDNA, indicating
      that the extreme affinity of p53 for hcDNA is likely due to the binding of the
      protein to the hemicatenane. Although binding of p53 to hcDNA occurs in the
      absence of the nonspecific DNA-binding extreme carboxy-terminal regulatory domain
      (30-C, residues 363-393), the isolated 30-C domain (but not the sequence-specific
      p53 "core domain", residues 94-312) can also bind hcDNA. Only the full-length p53
      can form stable ternary complexes with hcDNA and HMGB1. The possible biological
      relevance of p53 and HMGB1 binding to hemicatenanes is discussed.

PMID- 15170358
TI  - Effector-mediated alteration of substrate orientation in cytochrome P450 2C9.
AB  - Cytochrome P450 2C9 (CYP2C9)-mediated flurbiprofen 4'-hydroxylation is activated
      by the presence of dapsone resulting in reduction of the K(m) for flurbiprofen
      hydroxylation and an increase in V(m). Previous spectral binding studies have
      demonstrated that the binding of flurbiprofen with CYP2C9 is increased (decrease
      in K(S)) by the presence of dapsone. We hypothesized that the two compounds are
      simultaneously in the active site with the presence of dapsone causing
      flurbiprofen to be oriented more closely to the heme. T(1) relaxation rates
      determined by NMR were used to estimate the distances of protons on these
      compounds from the paramagnetic heme-iron center. Samples contained 0.014 microM
      CYP2C9 and 145 microM flurbiprofen in the presence and absence of 100 microM
      dapsone. Estimated distances of various flurbiprofen protons from the heme ranged
      from 4.2 to 4.5 A in the absence of dapsone and from 3.2 to 3.8 A in the presence
      of dapsone. The 4' proton of flurbiprofen, the site of metabolism, showed one of
      the greatest differences in distance from the heme in the presence of dapsone,
      3.50 A, as compared to the absence of dapsone, 4.41 A. Dapsone protons were less
      affected, being 4.40 A from the heme in the absence of flurbiprofen and 4.00-4.01
      A from the heme in the presence of flurbiprofen. Molecular modeling studies were
      also performed to corroborate the relative orientations of flurbiprofen and
      dapsone in the active site of CYP2C9. Shift of the 4' proton of flurbiprofen
      closer to the heme iron of CYP2C9 in the presence of dapsone may play a role in
      activation.

PMID- 15170361
TI  - Biologic agents for the treatment of juvenile rheumatoid arthritis: current
      status.
AB  - Biologic therapies, primarily anticytokine therapies, are being increasingly used
      in patients with juvenile rheumatoid arthritis (JRA). Levels of a variety of
      proinflammatory cytokines have been shown to be elevated in the peripheral blood
      and synovial fluid and tissue in children with JRA. In a blinded, randomized,
      controlled trial in children with severe, long-standing, polyarticular-course JRA
      not responsive to standard therapies, etanercept showed a statistically
      significantly greater response rate than placebo. Approximately 75% of these
      children responded to etanercept. Etanercept has been efficacious in 50-60% of
      children with active systemic JRA in open clinical trials with acceptable
      tolerance. Adverse events seen in children treated with etanercept have been
      similar in type and frequency to those reported in adults. Infliximab has been
      studied in several open clinical trials in both polyarticular and systemic JRA
      and found to, overall, have demonstrated efficacy in approximately 60% of
      patients. Approximately 3-5% of patients have demonstrated infusion reactions or
      frank allergic reactions and 9% developed new autoantibodies. Anakinra has been
      studied in children with polyarticular JRA. Approximately 65% of patients
      developed injection-site reactions and 68% demonstrated a response to the
      medication. Anakinra may have increased efficacy in systemic JRA. Interleukin
      (IL)-6 is highly related to the systemic disease manifestations in systemic JRA
      and two patients treated with a monoclonal antibody to the IL-6 receptor have
      demonstrated significant improvement with prolonged clinical control with
      continued treatment. A particular pediatric concern is the effect of
      immunosuppressive biologics in children who are exposed to or develop varicella.
      These children should be treated, both in terms of prophylaxis and aggressive
      antivaricella treatment, as for other immunosuppressed children. Anticytokine
      biologics have demonstrated great promise in the treatment of JRA and a variety
      of other pediatric rheumatic diseases, although at this time the randomized,
      placebo-controlled data are limited only to etanercept in children with
      polyarticular JRA. Randomized trials are ongoing to better define both the
      efficacy and safety of these novel treatments for children with JRA and other
      rheumatic diseases.

PMID- 15170362
TI  - Triple nucleoside reverse transcriptase inhibitor therapy in children.
AB  - Much of the success attributed to HIV therapy in the last few years has resulted
      from improved ways of using existing drugs in combination therapy regimens. The
      availability of new, more potent drugs such as protease inhibitors and more
      accurate viral load tests to aid decisions to start or change treatment has also
      contributed to the success. Published recommendations for pediatric HIV therapy,
      generated by a panel of experts and specialists, are readily available and
      regularly updated. Preferred regimens of 'potent' therapy (referred to as highly
      active antiretroviral therapy, or HAART) currently consist of two nucleoside
      reverse transcriptase inhibitors (NRTIs) combined with either a non-nucleoside
      reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. More intense
      four-drug regimens using an NNRTI or a second protease inhibitor as a fourth drug
      are being evaluated. Problems with HAART include: unpalatable drug formulations
      and adverse effects, coupled with lack of data on the pharmacokinetics, efficacy,
      and safety of various drug combinations. Adherence is a major factor influencing
      the efficacy and outcome of antiretroviral therapy. Many children cannot adhere
      to complex multidrug regimens, which cause virologic failure, despite excellent
      CD4+ cell count responses. This means a rapid progression through the limited
      number of treatment regimens available. Simpler regimens such as those containing
      three NRTIs have been proposed as a method of treatment that will allow
      suppression of the virus, yet circumvent many of the problems previously
      mentioned. An additional benefit would be the preservation of antiretroviral
      drugs from other classes for future treatment options if required. The major
      advantages of triple NRTI regimens are the simplicity of the regimen, good
      tolerability, few drug-drug interactions, and infrequent adverse effects coupled
      with a low pill burden. However, abacavir hypersensitivity remains a major
      problem. Up to 3% of patients may develop an early idiosyncratic hypersensitivity
      reaction - fever, malaise, and mucositis with or without rash, which can progress
      to more advanced stages of shock and death. A major concern is the apparently
      inferior virologic control of triple NRTI therapy as demonstrated in the AIDS
      Clinical Trials Group A5095 study with zidovudine/lamivudine/abacavir (Trizivir)
      combination in adults. Such a combination should only be considered in special
      situations. Examples cited include informed patient choice based on anticipated
      poor adherence on other treatment regimens, or if concomitant drugs such as
      tuberculosis medication are prescribed. The low pill burden of triple NRTI
      regimens (especially if combined in a single pill such as Trizivir), offers hope
      that regimen simplification may still be possible in the future.

PMID- 15170363
TI  - Long-acting beta 2-adrenoceptor agonists and exercise-induced asthma: lessons to
      guide us in the future.
AB  - The safety and efficacy of long-acting beta(2)-adrenoceptor agonists (LABAs)
      taken intermittently for the prevention of exercise-induced asthma (EIA) in
      children is well established. However, the safety and efficacy of LABAs taken
      twice daily, either alone or in combination with inhaled corticosteroids, for the
      prevention of EIA is not as clear because of issues of tolerance (defined as
      being less responsive to the influence of LABAs). There have been many
      observations on short-acting beta(2)-adrenoceptor agonists (SABAs) and EIA that
      should have alerted us to the potential for tolerance and desensitization to
      occur with LABAs. For example, we expected that the use of LABAs for EIA would
      overcome the problem of the short duration of protection of SABAs, and to some
      extent they have. The protective period of a LABA is two to three times longer in
      duration than that of a SABA. However, when a LABA is taken daily it is apparent
      that the duration of its protective effect is reduced and there is a risk of EIA
      occurring well within the 12-hour administration schedules. Furthermore, daily
      use of LABAs attenuates the bronchodilator effect of SABAs, an effect that is
      greater the more severe the bronchoconstriction. This 'tolerance' increases both
      the time and the amount of therapy that is needed to recover from
      bronchoconstriction, and thus, could potentially impact on the success of rescue
      therapy should severe EIA occur. The daily use of LABAs also increases the
      sensitivity of the bronchial smooth muscle to contractile agents. This increase
      in sensitivity is almost equivalent to the extent to which inhaled
      corticosteroids reduce sensitivity to the same contractile agents. The increased
      sensitivity to contractile agents may occur either by a reduction in the
      inhibitory effect of beta(2)-adrenoceptor agonists on release of mediators from
      mast cells or by a direct effect on the bronchial smooth muscle. These unwanted
      effects of LABAs are not necessarily reduced by concomitant treatment with
      inhaled corticosteroids. As the number of children being treated with LABAs
      increases, it is predicted that problems with breakthrough EIA will also
      increase. We need to know the percentage of children taking a LABA daily who are
      requiring either extra doses of a beta(2)-adrenoceptor agonist to prevent (or
      reverse) EIA or other provocative stimuli. If this percentage is significant then
      we may need to reconsider the position of LABAs in the treatment of children with
      asthma who regularly perform strenuous physical activity.

PMID- 15170364
TI  - Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial
      virus infection.
AB  - Palivizumab (Synagi) is a humanized monoclonal antibody that provides
      immunoprophylaxis against serious lower respiratory tract infections (LRTIs)
      caused by respiratory syncytial virus (RSV). RSV is the leading cause of
      hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In
      two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg
      every 30 days for 5 months significantly reduced RSV-related hospitalizations by
      55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic
      lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically
      significant congenital heart disease (HSCHD). Reductions were statistically
      significant versus placebo in infants with BPD/CLD, with all degrees of
      prematurity, and with acyanotic/other heart disease. Palivizumab was generally
      well tolerated, with < or =1.9% of recipients discontinuing treatment for
      tolerability reasons. In placebo-controlled trials, the most common potentially
      drug-related adverse events were fever, nervousness, injection-site reactions,
      and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients
      in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials.
      Very few serious potentially drug-related adverse events occurred in clinical
      trials; four occurred in 2 of 285 patients in one open-label trial. No
      significant anti-palivizumab antibodies developed during palivizumab use.
      Palivizumab trough serum concentrations were below the recommended 40 microg/mL
      in about 33% and up to 14% of children prior to their second and third
      palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per
      hospitalization averted was generally lowest in the highest-risk infants. Drug
      cost was generally the most influential factor in sensitivity analyses. In
      conclusion, prophylaxis with palivizumab significantly reduces the incidence of
      RSV-related hospitalization relative to placebo and is generally well tolerated
      in high-risk infants aged <2 years, including those with prematurity and BPD/CLD
      or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab
      is approved for use in these patients. Other high-risk infants in whom
      palivizumab has not been formally assessed, such as those with immunodeficiency,
      cystic fibrosis, or location-specific risk factors (including extended hospital
      stays) might potentially benefit from palivizumab. The use of palivizumab in
      these other high-risk populations is likely to be determined as much by
      pharmacoeconomic considerations as by efficacy outcomes.

PMID- 15170366
TI  - Effect of haemodialysis on the pharmacokinetics of antineoplastic drugs.
AB  - Since renal failure itself creates an immunocompromised situation, malignant
      tumours in haemodialysis patients are increasing due to the prolonged lifespan of
      these patients. In treating these patients with anticancer agents, dosage
      reduction is often recommended to avoid adverse drug reactions, particularly for
      drugs with extensive renal excretion. On the other hand, if an anticancer drug is
      removed significantly by haemodialysis, dosage increase would be required to
      ensure adequate therapeutic efficacy. We address in this review the clinical
      pharmacokinetic aspects of antineoplastic therapy, and the application of
      pharmacokinetic principles to the adjustment of dosage of anticancer agents in
      haemodialysis patients.

PMID- 15170367
TI  - Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer.
AB  - OBJECTIVE: To characterise the pharmacokinetics of a long-acting formulation of
      fulvestrant following intramuscular administration of single and multiple doses.
      STUDY DESIGN: Pharmacokinetic investigations of single and multiple doses of
      fulvestrant were conducted within two global phase III efficacy studies that
      compared intramuscular fulvestrant with oral anastrozole in postmenopausal women
      with hormone-sensitive advanced breast cancer (study 0020, conducted in Europe,
      Australia and South Africa, and study 0021, conducted in North America). METHODS:
      Patients received once-monthly intramuscular injections of fulvestrant 250 mg (1
      x 5 mL for < or =21 months in study 0020; 2 x 2.5 mL for < or =30 months in study
      0021). Serial blood samples were collected for the first 28 days after the
      initial dose and immediately prior to all subsequent monthly doses. Plasma
      fulvestrant concentrations were determined by high-performance liquid
      chromatography-tandem mass spectrometry. PATIENTS: Twenty-six (study 0020) and
      193 (study 0021) postmenopausal women, comprising the pharmacokinetic subgroups
      of the phase III efficacy trials, were studied. Patients had shown disease
      progression or recurrence following previous hormonal therapy for advanced
      disease or had relapsed after adjuvant endocrine therapy with a nonsteroidal
      antiestrogen. OUTCOME MEASURES AND RESULTS: For single-dose fulvestrant 250 mg,
      area under the concentration-time curve from time zero to 28 days (AUC(28)),
      maximum observed plasma concentration (C(max)), minimum observed plasma
      concentration at 28 days (C(min)) and time to maximum plasma concentration
      (t(max)) were determined. For multiple-dose fulvestrant 250 mg once monthly,
      steady-state trough concentrations (C(trough)) were determined. Plasma
      fulvestrant concentrations reached a peak at a median of 7 days (range 2-8 days)
      postdose, and declined biexponentially with a slower phase commencing
      approximately 2-3 weeks postdose. Intersubject variability in C(max) and AUC(28)
      was approximately 6-fold and 4-fold, respectively. Mean parameters for single
      dose fulvestrant were: AUC(28), 148 microg. day/L; C(max), 8.2 microg/L; C(min),
      2.6 microg/L; t(max), 7.0 days. Geometric mean C(trough) increased from 2.57 to
      6.15 microg/L (study 0020) and from 2.38 to 6.52 microg/L (study 0021) over the
      first 6 months, reaching steady-state concentrations of approximately 6-7
      microg/L (study 0020) or 9 microg/L (study 0021). Preliminary pharmacokinetic
      analysis, using a naive pooled data approach, suggests that observed single- and
      multiple-dose plasma profiles can be adequately described with a two-compartment
      kinetic model. Model-generated steady-state AUC(28) values were approximately 300
      microg. day/L. CONCLUSIONS: The intramuscular formulation of fulvestrant displays
      predictable kinetics and approximately 2-fold accumulation on administration once
      monthly. At the proposed therapeutic dosage (250 mg once monthly), plasma
      fulvestrant concentrations are maintained within a narrow range throughout the
      administration interval, thus ensuring stable systemic drug exposure during long
      term treatment.

PMID- 15170369
TI  - Short forms of membrane receptors: generation and role in hormonal signal
      transduction.
AB  - This review highlights the generation of various types of short forms of membrane
      hormonal receptors and the mode of regulation of their tissue-specific patterns.
      The short forms of membrane receptors are classified on the basis of localization
      of missing functional fragments. The review provides examples of tissues for
      which expression of short forms may serve as a marker of changes of ontogenetic
      stage, physiological state, or the development of pathological process. The short
      forms of receptors are shown to participate in determining tissue-specificity and
      efficacy of hormonal signal transduction, as well as in transport of hormones
      within cell, through physiological barriers, and in blood circulation.
      Peculiarities of signal transduction pathways for short receptor forms and
      potential physiological significance of these forms are analyzed. It is concluded
      that the ratio of long and short receptor forms may serve as a key marker of
      dynamic changes of differentiation stage and alterations of metabolic and
      proliferative activity of tissues under normal and pathologic conditions, and
      thus to be an important indicator of therapeutic effect for many pathological
      processes.

PMID- 15170368
TI  - Insulin disposition in the lung following oral inhalation in humans : a meta
      analysis of its pharmacokinetics.
AB  - BACKGROUND: Oral inhalation of insulin potentially offers non-invasive treatment
      and better glycaemic control in diabetes by virtue of its apparently faster
      absorption into the systemic circulation compared with subcutaneous injection.
      Nevertheless, the lung kinetics of inhaled insulin in humans have yet to be fully
      clarified because of the complexity of insulin-glucose (patho)physiology and the
      difficulty in approximating the inhaled dose. As a result, there remains
      considerable debate on the mechanisms of absorption and metabolism of insulin in
      the lung. OBJECTIVES: To develop and apply a physiologically realistic insulin
      glucose kinetic model to a meta-analysis of insulin-glucose profiles from well
      controlled clinical studies of inhaled insulin published in the literature, and
      thereby, to derive the kinetic descriptors of insulin in the lung following
      inhalation through curve fitting. MODEL DEVELOPMENT: The model assumed first
      order absorption (k(a,L)) and parallel non-absorptive loss (k(mm,L)), the latter
      primarily occurring via metabolism and mucociliary clearance in the lung,
      alongside two systemic compartments. Where necessary, glucose-dependent
      endogenous pancreatic insulin secretion was also taken into account by using
      blood glucose data as the second independent variable. RESULTS: Despite the
      model's simplicity and the use of mean data, 16 insulin-glucose profiles from ten
      clinical studies were successfully fitted to the model, yielding values for the
      rate constants k(a,L) and k(mm,L). Whole serum insulin profiles were rate
      determined by k(a,L) and k(mm,L) combined, representing 'flip-flop'
      pharmacokinetics. The best estimate for k(a,L) was found to be 0.020-0.032 h(-1),
      effectively unchanged across doses (0.3-1.8 IU/kg), formulations (powder vs
      liquid) and subjects (healthy vs diabetic), suggesting passive diffusive
      absorption of insulin from the lung. In contrast, the values for k(mm,L) were
      much larger (0.5-1.6 h(-1)) and decreased with increasing inhaled dose.
      Therefore, it is likely that dose-dependent saturable lung metabolism controls
      the value of k(mm,L), alongside mucociliary clearance. As a result, the absolute
      bioavailability ranged from 1.5% to 4.8%. The modelling analysis also enabled
      derivation of increased values for both k(a,L) and k(mm,L) as a possible cause of
      faster absorption for deep inspiratory manoeuvres and increased absorption in
      smokers, and faster and increased absorption for insulin lispro. CONCLUSIONS:
      Although some of these results need to be substantiated experimentally, it
      appears that this modelling analysis has enabled unification of the literature
      information associated with the kinetics and mechanisms of insulin disposition in
      the lung following inhalation in humans.

PMID- 15170370
TI  - Chimerogenesis in estimation of specificity and pathway directions for cytochrome
      p45017alpha catalyzed reactions.
AB  - Cytochrome P45017alpha is a key enzyme in steroid hormone biosynthesis. It
      catalyzes the reaction of 17alpha-hydroxylation of progesterone (P4) and
      pregnenolone (P5) and the 17,20-lyase reaction resulting in side chain cleavage
      of C21 steroids to form C19 steroids. Depending on the activity of cytochrome
      P45017alpha, steroid hormone biosynthesis pathways are directed either for
      biosynthesis of mineralocorticoids and glucocorticoids or sex hormones. The
      formation of sex hormones starts from biosynthesis of androstenedione.
      Androstenedione formation is a result of two reactions: 17,20-lyase reaction of
      17alpha-hydroxyprogesterone (Delta4-pathway) and 3beta-hydroxysteroid
      dehydrogenase/Delta4,Delta5-isomerase reaction using dehydroepiandrosterone as
      substrate (Delta5-pathway). In case of exclusive direction of the 17,20-lyase
      reaction either through the Delta4- or the Delta5-pathway, the formation of sex
      hormones depends more on specificity and activity of 3beta-hydroxysteroid
      dehydrogenase/Delta4,Delta5-isomerase. Depending on species, the cytochromes
      P45017alpha can utilize as a substrate for 17,20-lyase activity Delta4-steroids,
      Delta5-steroids, or both types of steroids. To identify the structural elements
      of cytochrome P45017alpha responsible for substrate recognition, in the present
      work we used exchange of homologous fragments of cytochrome P45017alpha having
      different types of activities. We engineered more than 10 different types of
      chimeric cytochrome P45017alpha. Chimeric cytochromes P45017alpha have been
      expressed in E. coli and purified. The expression of chimeric cytochrome
      P45017alpha with the point of exchange between exons III and IV results in
      inability of the recombinant hemeprotein to properly bind heme. The determination
      of activity of chimeric cytochromes P45017alpha shows that the structural element
      responsible for switching activity between Delta4- or Delta5-pathway is located
      in the region of polypeptide chain coded by exons II-V of CYP17 gene.

PMID- 15170372
TI  - Effect of chlorpromazine on human and murine intracellular carboxylesterases.
AB  - Clinical use of chlorpromazine (CPZ), an antipsychotic drug, is limited due to
      its hepatotoxicity. CPZ is found to inhibit in vitro intracellular
      carboxylesterases (CE), such as alpha-naphthyl acetate esterase, naphthol AS-D
      chloroacetate esterase, and alpha-naphthyl butyrate esterase in polymorphonuclear
      neutrophils, hepatocytes, and neuronal brain cells from mice. CPZ inhibits CE of
      all these cell types, whereby the degree of the inhibition depends on the
      incubation time and CPZ concentration. The polymorphonuclear neutrophils are most
      sensitive to CPZ. Comparable results were obtained with polymorphonuclear
      neutrophils from mice and humans. Since leukocytes are much more available than
      hepatocytes or neuronal cells in humans, we assume that CE in peripheral blood
      leukocytes (neutrophils and monocytes) can be used as markers for indication of
      pending liver damage by CPZ.

PMID- 15170371
TI  - Purification and properties of isocitrate lyase from pupas of the butterfly
      Papilio machaon L.
AB  - Key enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase, were
      identified in pupas of the butterfly Papilio machaon L. The activities of these
      enzymes in pupas were 0.056 and 0.108 unit per mg protein, respectively.
      Isocitrate lyase was purified by a combination of various chromatographic steps
      including ammonium sulfate fractionation, ion-exchange chromatography on DEAE
      Toyopearl, and gel filtration. The specific activity of the purified enzyme was
      5.5 units per mg protein, which corresponded to 98-fold purification and 6%
      yield. The enzyme followed Michaelis-Menten kinetics (Km for isocitrate, 1.4 mM)
      and was competitively inhibited by succinate (Ki = 1.8 mM) and malate (Ki = 1
      mM). The study of physicochemical properties of the enzyme showed that it is a
      homodimer with a subunit molecular weight of 68 +/- 2 kD and a pH optimum of 7.5
      (in Tris-HCl buffer).

PMID- 15170373
TI  - Purification and properties of exopolyphosphatase from the cytosol of
      Saccharomyces cerevisiae not encoded by the PPX1 gene.
AB  - A novel exopolyphosphatase has been isolated from the cytosol of Saccharomyces
      cerevisiae grown to the stationary phase after its transfer from phosphate
      deficient to complete medium. The PPX1 gene responsible for 40-kD
      exopolyphosphatase of the cytosol does not encode it. Specific activity of the
      preparation is 150 U/mg, purification degree is 319, and the yield is 16.9%. The
      minimal molecular mass of the active but unstable enzyme complex is approximately
      125 kD. A stable enzyme complex with a molecular mass of approximately 500 kD is
      composed of two polypeptides of approximately 32 and 35 kD and apparently
      polyphosphates (polyP). Unlike the enzyme encoded by PPX1, the high-molecular
      mass exopolyphosphatase is slightly active with polyP3, not inhibited by
      antibodies suppressing the activity of 40-kD exopolyphosphatase, inhibited by
      EDTA, and stimulated by divalent cations to a lesser extent. The high-molecular
      mass exopolyphosphatase hydrolyzes polyP with an average chain length of 208 to
      15 phosphate residues to the same extent, but is inactive with ATP, PPi, and p
      nitrophenyl phosphate. The activity with polyP3 is 13% of that with polyP208. The
      Km values for polyP208, polyP15, and polyP3 hydrolysis are 3.5, 75, and 1100
      microM, respectively. The enzyme is most active at pH approximately 7. Co2+ at
      the optimal concentration of 0.1 mM stimulates the activity 6-fold, while Mg2+ at
      the optimal concentration of 1 mM enhances it 2-fold. The enzyme under study is
      similar in some properties to an exopolyphosphatase purified earlier from yeast
      vacuoles.

PMID- 15170375
TI  - Effects of N-terminal deletion mutation on rabbit muscle lactate dehydrogenase.
AB  - Deletion mutants of rabbit muscle lactate dehydrogenase (LDH) were constructed
      using polymerase chain reaction (PCR) to study the roles of N-terminal residues.
      The coding sequences of the first 5 (LD5) and 10 (LD10) amino acids of the N
      terminus were deleted and the gene was inserted into the prokaryotic expression
      vector pET21b. The mutant enzymes were expressed in E. coli BL21/DE3 and were
      purified. Then their characteristics and stabilities were studied. The results
      showed LDH was completely inactivated when the first 10 N-terminal amino acid
      residues were removed, but the mutant (LD10) could have partially restored
      activity in the presence of structure-making ions. The removal of the first 5 and
      10 N-terminal amino acid residues did not affect the aggregation state of the
      enzyme, that is, LD5 and LD10 were still tetramers. The stabilities of
      recombinant wild-type LDH (RW-LD), LD5, and LD10 were compared by incubating them
      at low pH, elevated temperature, and high GuHCl. The results showed that the N
      terminal deletion mutants were more sensitive to denaturing environments; they
      were easily inactivated and unfolded. Their instability increased and their
      ability to refold decreased with the increased number of amino acid residues
      removed from the N-terminus of LDH. These results confirm that the N-terminus of
      LDH plays a crucial role in stabilizing the structure and in maintaining the
      function of the enzyme.

PMID- 15170365
TI  - Drug transfer and metabolism by the human placenta.
AB  - The major function of the placenta is to transfer nutrients and oxygen from the
      mother to the foetus and to assist in the removal of waste products from the
      foetus to the mother. In addition, it plays an important role in the synthesis of
      hormones, peptides and steroids that are vital for a successful pregnancy. The
      placenta provides a link between the circulations of two distinct individuals but
      also acts as a barrier to protect the foetus from xenobiotics in the maternal
      blood. However, the impression that the placenta forms an impenetrable obstacle
      against most drugs is now widely regarded as false. It has been shown that that
      nearly all drugs that are administered during pregnancy will enter, to some
      degree, the circulation of the foetus via passive diffusion. In addition, some
      drugs are pumped across the placenta by various active transporters located on
      both the fetal and maternal side of the trophoblast layer. It is only in recent
      years that the impact of active transporters such as P-glycoprotein on the
      disposition of drugs has been demonstrated. Facilitated diffusion appears to be a
      minor transfer mechanism for some drugs, and pinocytosis and phagocytosis are
      considered too slow to have any significant effect on fetal drug concentrations.
      The extent to which drugs cross the placenta is also modulated by the actions of
      placental phase I and II drug-metabolising enzymes, which are present at levels
      that fluctuate throughout gestation. Cytochrome P450 (CYP) enzymes in particular
      have been well characterised in the placenta at the level of mRNA, protein, and
      enzyme activity. CYP1A1, 2E1, 3A4, 3A5, 3A7 and 4B1 have been detected in the
      term placenta. While much less is known about phase II enzymes in the placenta,
      some enzymes, in particular uridine diphosphate glucuronosyltransferases, have
      been detected and shown to have specific activity towards marker substrates,
      suggesting a significant role of this enzyme in placental drug detoxification.
      The increasing experimental data on placental drug transfer has enabled
      clinicians to make better informed decisions about which drugs significantly
      cross the placenta and develop dosage regimens that minimise fetal exposure to
      potentially toxic concentrations. Indeed, the foetus has now become the object of
      intended drug treatment. Extensive research on the placental transfer of drugs
      such as digoxin and zidovudine has assisted with the safe treatment of the foetus
      with these drugs in utero. Improved knowledge regarding transplacental drug
      transfer and metabolism will result in further expansion of pharmacological
      treatment of fetal conditions.

PMID- 15170374
TI  - Characteristics of non-opioid beta-endorphin receptor.
AB  - Tritium-labeled selective agonist of non-opioid beta-endorphin receptor, the
      decapeptide immunorphine ([3H]SLTCLVKGFY) with specific activity of 24 Ci/mmol
      has been prepared. By its use, non-opioid beta-endorphin receptors were revealed
      and characterized on mouse peritoneal macrophages and rat myocardium, spleen,
      adrenal, and brain membranes. The non-opioid beta-endorphin receptor of
      macrophages has in addition to immunorphine (Kd of the [3H]immunorphine-receptor
      complex was 2.4 +/- 0.1 nM) and beta-endorphin (Ki of the [3H]immunorphine
      specific binding was 2.9 +/- 0.2 nM) a high affinity for Fc-fragment of human
      IgG1, pentarphine (VKGFY), cyclopentarphine [cyclo(VKGFY)], and [Pro3]pentarphine
      (VKPFY) (Ki values were 0.0060 +/- 0.0004, 2.7 +/- 0.2, 2.6 +/- 0.2, and 2.8 +/-
      0.2 nM, respectively) and is insensitive to naloxone and [Met5]enkephalin (Ki >
      100 microM). Treatment of macrophages with trypsin resulted in the loss of their
      ability for the specific binding of [3H]immunorphine. Values of the specific
      binding of 8.4 nM [3H]immunorphine to rat adrenal, spleen, myocardium, and brain
      membranes were determined to be 1146.0 +/- 44.7, 698.6 +/- 28.1, 279.1 +/- 15.4,
      and 172.2 +/- 1.8 fmol/mg protein, respectively. Unlabeled beta-endorphin,
      pentarphine, [Pro3]pentarphine, cyclopentarphine, cyclodipentarphine
      [cyclo(VKGFYVKGFY)], and Fc-fragment of IgG1 inhibited the binding of
      [3H]immunorphine to membranes from these organs. No specific binding of
      [3H]immunorphine to rat liver, lung, kidney, and intestine membranes was found.

PMID- 15170376
TI  - Structure of lipid A from the marine gamma-proteobacterium Marinomonas vaga ATCC
      27119T lipopolysaccharide.
AB  - The chemical structure of a novel lipid A obtained as a major component on
      hydrolysis of LPS from the marine gamma-proteobacterium Marinomonas vaga ATCC
      27119T with 1% AcOH was determined. Using chemical analysis and NMR data, it was
      shown to be beta-1,6-glucosaminobiose 1-phosphate acylated with R-3
      hydroxydecanoic acid (at position 3), and R-3-dodecanoyloxydecanoic (or R-3
      decanoyloxydecanoic) acid and R-3-(R-3-hydroxydecanoyl)oxydecanoic acids (at the
      2- or 2;-positions). The absence of a fatty acid at the 3;-position and a
      phosphoryl group at the 4;-position, and also the presence of R-3-acyloxyalkanoic
      acid with R-3-hydroxyalkanoic acid as the secondary acid are unique features
      distinguishing the M. vaga lipid A from other ones.

PMID- 15170378
TI  - Purification and characterization of serine proteinase 2 from Bacillus
      intermedius 3-19.
AB  - A proteinase secreted in the late stationary phase was isolated from the culture
      fluid of Bacillus intermedius 3-19 by ion-exchange chromatography on CM-cellulose
      followed by FPLC on a Mono S column. The enzyme was completely inhibited by the
      serine proteinase inhibitors diisopropyl fluorophosphate and phenylmethylsulfonyl
      fluoride. The maximum proteolytic activity against the synthetic chromogenic
      substrate Z-Ala-Ala-Leu-pNA was observed at pH 9.0. The molecular weight of the
      enzyme is 28 kD and its isoelectric point is 9.2. We have also determined pH- and
      thermostability and Km and kcat of this proteinase. The enzyme has been
      classified as a thiol-dependent serine proteinase. N-Terminal amino acid sequence
      (10 residues) and amino acid composition of the protein were also determined. By
      the mode of hydrolysis of peptide bonds in the oxidized B-chain of insulin, this
      enzyme is similar to the thiol-dependent serine proteinase 1 from B. intermedius
      3-19 secreted during vegetative growth.

PMID- 15170379
TI  - Comparative characterization of extracellular and intracellular hydrocarbons of
      Clostridium pasteurianum.
AB  - Extracellular and intracellular hydrocarbons produced by Clostridium pasteurianum
      VKM 1774 during cultivation on glucose-containing media in an argon atmosphere or
      in the presence of carbon dioxide and molecular hydrogen were analyzed by gas
      liquid chromatography. Intracellular hydrocarbons were 50-55% (C25-C35) n
      alkanes. Carbon dioxide and molecular hydrogen stimulated synthesis of
      extracellular hydrocarbons, which comprised 90-95% (C11-C24) n-alkanes.

PMID- 15170377
TI  - Inhibition of gap junction intercellular communications in cell culture by
      polycyclic aromatic hydrocarbons (PAH) in the absence of PAH metabolism.
AB  - We have studied the effect of polycyclic aromatic hydrocarbons (PAH) on gap
      junction intercellular communications (GJIC) in culture of hepatoma cells Hep G2
      and G27. Carcinogenic PAH inhibited GJIC in both cultures in contrast to non
      carcinogenic PAH. We showed that both constitutive and inducible expressions of
      mRNAs of Ah receptor and cytochrome P4501A1 (the main isoform involved in PAH
      metabolism) were absent in hepatoma G27 cells. We concluded that the initial, non
      metabolized molecules of carcinogenic PAH are responsible for changes in GJIC
      through interaction with an unknown factor in the cellular membrane.

PMID- 15170381
TI  - DNA polymerase iota-like activity in crude cell extracts of different mouse
      organs.
AB  - The recently discovered DNA polymerase iota differs greatly from the numerous
      eukaryotic and prokaryotic DNA polymerases known previously in its ability to
      catalyze error-prone DNA synthesis. Using homogeneous preparations of the enzyme,
      it was shown previously that DNA polymerase iota incorporated preferentially dGMP
      opposite the thymidine of the template in the growing DNA chain. To elucidate the
      role of this enzyme in the mammals, its activity was assayed in crude cell
      extracts of different mouse organs. It is shown that the extracts of the brain
      and testis cells exhibit the highest activity of DNA polymerase iota, which is
      not in agreement with the results of other authors. The data suggest that the
      tissue specific expression of DNA polymerase iota is regulated to a significant
      degree at the posttranscriptional and posttranslational levels.

PMID- 15170380
TI  - Functional relationship between Na/K-ATPase and NMDA-receptors in rat cerebellum
      granule cells.
AB  - Activation of rat cerebellum granule cells by N-methyl-D-aspartate (NMDA, 10(-4)
      10(-3) M) results in progressive increase in reactive oxygen species (ROS) and
      suppression of the ouabain-sensitive part of Na/K-ATPase activity. When Na/K
      ATPase was inhibited by high ouabain concentrations (10(-5)-5 x 10(-4) M), an
      increase in stationary ROS level in neuronal cells was noted, this effect being
      attenuated by NMDA antagonists, MK-801 and D-AP5. It is concluded that in
      cerebellum neurons, ouabain-resistant Na/K-ATPase is responsible for suppression
      of intracellular level of ROS, which, in turn, inhibit ouabain-sensitive Na/K
      ATPase.

PMID- 15170382
TI  - Cationic inhibitors of serine proteinases from buckwheat seeds: study of their
      interaction with exogenous proteinases.
AB  - The inhibition of exogenous serine proteinases of different origin by cationic
      protease inhibitors BWI-1c, -2c, -3c, and -4c from buckwheat (Fagopyrum
      esculentum Moench) seeds has been studied. High efficiency of the inhibitors in
      binding bovine trypsin and chymotrypsin as well as their broad antiprotease
      effect, including inhibition of proteinases secreted by fungi and bacteria, has
      been demonstrated. According to the data obtained, it is proposed that cationic
      inhibitors from buckwheat seeds may participate in the defense of plants against
      fungal and bacterial infection.

PMID- 15170384
TI  - Kinetics of chemical modification of arginine residues in mitochondrial creatine
      kinase from bovine heart: evidence for negative cooperativity.
AB  - The kinetics of chemical modification of arginine residues in mitochondrial
      creatine kinase (mit-CK) from beef heart by 4-hydroxy-3-nitrophenylglyoxal (HNPG)
      have been studied with simultaneous registration of enzyme inactivation.
      Experiments showed that complete inactivation of mit-CK corresponded to
      modification of two arginine residues per mit-CK monomer. The data on the
      modification kinetics can be described by the sum of two exponential terms and
      suggest strong negative cooperativity in the binding of HNPG to arginine
      residues. The rate constants for the fast and slow phases of modification differ
      by a factor of about 50. The corresponding rate constants for inactivation differ
      by a factor of about 30. The rate constant for the slow stage of inactivation is
      twice as large as that for the rate constant for the slow stage of modification,
      i.e., the inactivation process is ahead of the modification process.

PMID- 15170383
TI  - Reduction of photosystem I reaction center in DrgA mutant of the cyanobacterium
      Synechocystis sp. PCC 6803 lacking soluble NAD(P)H:quinone oxidoreductase.
AB  - Photoautotrophically grown cells of the cyanobacterium Synechocystis sp. PCC 6803
      wild type and the Ins2 mutant carrying an insertion in the drgA gene encoding
      soluble NAD(P)H:quinone oxidoreductase (NQR) did not differ in the rate of light
      induced oxygen evolution and Photosystem I reaction center (P700+) reduction
      after its oxidation with a white light pulse. In the presence of DCMU, the rate
      of P700+ reduction was lower in mutant cells than in wild type cells. Depletion
      of respiratory substrates after 24 h dark-starvation caused more potent decrease
      in the rate of P700+ reduction in DrgA mutant cells than in wild type cells. The
      reduction of P700+ by electrons derived from exogenous glucose was slower in
      photoautotrophically grown DrgA mutant than in wild type cells. The mutation in
      the drgA gene did not impair the ability of Synechocystis sp. PCC 6803 cells to
      oxidize glucose under heterotrophic conditions and did not impair the NDH-1
      dependent, rotenone-inhibited electron transfer from NADPH to P700+ in thylakoid
      membranes of the cyanobacterium. Under photoautotrophic growth conditions, NADPH
      dehydrogenase activity in DrgA mutant cells was less than 30% from the level
      observed in wild type cells. The results suggest that NQR, encoded by the drgA
      gene, might participate in the regulation of cytoplasmic NADPH oxidation,
      supplying NADP+ for glucose oxidation in the pentose phosphate cycle of
      cyanobacteria.

PMID- 15170385
TI  - Iron, nitric oxide, and myeloperoxidase in asthmatic patients.
AB  - Plasma nitric oxide (NO), myeloperoxidase (MPO), and iron (Fe) levels were
      determined in bronchial asthma. The relations among these parameters in different
      stages of asthma were interpreted. Their association with airway inflammation
      observed in patients with bronchial asthma as well as the roles and the
      contributions to the pathological processes were evaluated. A total of 62
      individuals, 32 asthmatics and 30 controls, were included into the scope of this
      study. Plasma nitric oxide metabolites (NOx) and MPO and Fe levels were
      determined by the Griess reaction, ELISA, and the automated TPTZ (2,4,6-tri[2
      pyridyl]-5-triazine) method, respectively. In the asthmatic individuals, plasma
      NOx, MPO, and Fe concentrations were 133 +/- 13 microM, 95 +/- 20 ng/ml, and 159
      +/- 20 microg/dl, respectively; in the control group these values were 82 +/- 11
      microM, 62 +/- 11 ng/ml, and 96 +/- 9 microg/dl. Increased values were detected
      for plasma MPO (p > 0.05), NOx (p < 0.01), and Fe (p < 0.01) concentrations in
      asthmatic individuals. Considering the facts that NO modulates the catalytic
      activity of MPO and induces the expression of heme oxygenase as important
      contributors to the mechanisms causing free Fe release, it is concluded that
      elevated NOx, MPO, and Fe levels observed in the asthmatic group act in a
      concerted manner and appear to be involved in the pathogenesis of asthma.

PMID- 15170387
TI  - Dual regulation of AP-2alpha transcriptional activation by poly(ADP-ribose)
      polymerase-1.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a co-activator for AP-2alpha (activator
      protein 2alpha)-mediated transcriptional activation. In the present study, we
      find that the role of PARP-1 in AP-2alpha transcription is distinctly dualistic
      with opposing effects. Separate regions of PARP-1 interact with AP-2alpha and
      independently control its transcriptional activation. The C-terminus containing
      the catalytic domain strongly interacts with AP-2alpha, whereas low-affinity
      binding is seen in the middle region, which includes the breast-cancer
      susceptibility gene 1 C-terminal domain and automodification region. The middle
      region enhances AP-2alpha transcription. Even portions of this region
      independently interact and have partial effects on transcription. The catalytic
      domain strongly poly-(ADP-ribosyl)ates AP-2alpha. This modification, on the other
      hand, affects its DNA binding. 3-Aminobenzamide and 6(5H)-phenanthridinone that
      inhibit the enzymic activity significantly enhance the binding of AP-2alpha to
      its target sequence and increase its transcriptional activity. The enzymic
      activity of PARP-1 is known to be induced by stress conditions that damage
      cellular DNA, and the poly(ADP-ribosyl)ation of target proteins is transient in
      nature with a half-life of less than a minute. We hypothesize that PARP-1
      enhances the transcriptional activity of AP-2alpha in normal circumstances,
      whereas its enzymic activity is used as a temporary shut-off mechanism during
      unfavourable conditions.

PMID- 15170388
TI  - Two related ARID family proteins are alternative subunits of human SWI/SNF
      complexes.
AB  - p270 (ARID1A) is a member of the ARID family of DNA-binding proteins and a
      subunit of human SWI/SNF-related complexes, which use the energy generated by an
      integral ATPase subunit to remodel chromatin. ARID1B is an independent gene
      product with an open reading frame that is more than 60% identical with p270. We
      have generated monoclonal antibodies specific for either p270 or ARID1B to
      facilitate the investigation of ARID1B and its potential interaction with human
      SWI/SNF complexes in vivo. Immunocomplex analysis provides direct evidence that
      endogenous ARID1B is associated with SWI/SNF-related complexes and indicates that
      p270 and ARID1B, similar to the ATPase subunits BRG1 and hBRM, are alternative,
      mutually exclusive subunits of the complexes. The ARID-containing subunits are
      not specific to the ATPases. Each associates with both BRG1 and hBRM, thus
      increasing the number of distinct subunit combinations known to be present in
      cells. Analysis of the panels of cell lines indicates that ARID1B, similar to
      p270, has a broad tissue distribution. The ratio of p270/ARID1B in typical cells
      is approx. 3.5:1, and BRG1 is distributed proportionally between the two ARID
      subunits. Analysis of DNA-binding behaviour indicates that ARID1B binds DNA in a
      non-sequence-specific manner similar to p270.

PMID- 15170386
TI  - 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a
      bifunctional enzyme that controls glycolysis.
AB  - Fru-2,6-P2 (fructose 2,6-bisphosphate) is a signal molecule that controls
      glycolysis. Since its discovery more than 20 years ago, inroads have been made
      towards the understanding of the structure-function relationships in PFK-2 (6
      phosphofructo-2-kinase)/FBPase-2 (fructose-2,6-bisphosphatase), the homodimeric
      bifunctional enzyme that catalyses the synthesis and degradation of Fru-2,6-P2.
      The FBPase-2 domain of the enzyme subunit bears sequence, mechanistic and
      structural similarity to the histidine phosphatase family of enzymes. The PFK-2
      domain was originally thought to resemble bacterial PFK-1 (6-phosphofructo-1
      kinase), but this proved not to be correct. Molecular modelling of the PFK-2
      domain revealed that, instead, it has the same fold as adenylate kinase. This was
      confirmed by X-ray crystallography. A PFK-2/FBPase-2 sequence in the genome of
      one prokaryote, the proteobacterium Desulfovibrio desulfuricans, could be the
      result of horizontal gene transfer from a eukaryote distantly related to all
      other organisms, possibly a protist. This, together with the presence of PFK
      2/FBPase-2 genes in trypanosomatids (albeit with possibly only one of the domains
      active), indicates that fusion of genes initially coding for separate PFK-2 and
      FBPase-2 domains might have occurred early in evolution. In the enzyme homodimer,
      the PFK-2 domains come together in a head-to-head like fashion, whereas the
      FBPase-2 domains can function as monomers. There are four PFK-2/FBPase-2
      isoenzymes in mammals, each coded by a different gene that expresses several
      isoforms of each isoenzyme. In these genes, regulatory sequences have been
      identified which account for their long-term control by hormones and tissue
      specific transcription factors. One of these, HNF-6 (hepatocyte nuclear factor
      6), was discovered in this way. As to short-term control, the liver isoenzyme is
      phosphorylated at the N-terminus, adjacent to the PFK-2 domain, by PKA (cAMP
      dependent protein kinase), leading to PFK-2 inactivation and FBPase-2 activation.
      In contrast, the heart isoenzyme is phosphorylated at the C-terminus by several
      protein kinases in different signalling pathways, resulting in PFK-2 activation.

PMID- 15170389
TI  - Interaction of the tyrosine phosphatase SHP-2 with Gab2 regulates Rho-dependent
      activation of the c-fos serum response element by interleukin-2.
AB  - Gab2 (Grb2-associated binder-2), a member of the IRS (insulin receptor
      substrate)/Gab family of adapter proteins, undergoes tyrosine phosphorylation in
      response to cytokine or growth factor stimulation and serves as a docking
      platform for many signal transduction effectors, including the tyrosine
      phosphatase SHP-2 [SH2 (Src homology 2)-domain-containing tyrosine phosphatase].
      Here, we report that, following IL-2 (interleukin-2) stimulation of human T
      lymphocytes, SHP-2 binds tyrosine residues 614 and 643 of human Gab2 through its
      N- and C-terminal SH2 domains respectively. However, the sole mutation of Tyr-614
      into phenylalanine is sufficient to prevent Gab2 from recruiting SHP-2.
      Expression of the Gab2 Tyr-614-->Phe (Y614F) mutant, defective in SHP-2
      association, prevents ERK (extracellular-signal-regulated kinase) activation and
      expression of a luciferase reporter plasmid driven by the c-fos SRE (serum
      response element), indicating that interaction of SHP-2 with Gab2 is required for
      ERK activation in response to IL-2. Further investigation of IL-2-dependent
      induction of SRE showed that expression of a constitutively active mutant of the
      RhoA GTPase synergizes with IL-2 for SRE-driven transcription, whereas a dominant
      negative mutant reduces the IL-2 response. Thus, in response to IL-2, full
      induction of the SRE requires ERK-dependent as well as Rho-dependent signals that
      target the Ets-box and the CArG-box respectively. We also report that the synergy
      between Gab2/SHP-2 and RhoA for IL-2-dependent CArG-box-driven transcription
      depends upon MEK (mitogen-activated protein kinase/ERK kinase) activation, and is
      likely to involve regulation of the serum response factor co-activator MAL. Our
      studies thus provide new insights into the role of Gab2 and SHP-2 in IL-2 signal
      transduction.

PMID- 15170390
TI  - Lipoprotein receptor binding, cellular uptake, and lysosomal delivery of fusions
      between the receptor-associated protein (RAP) and alpha-L-iduronidase or acid
      alpha-glucosidase.
AB  - Enzyme replacement therapy for lysosomal storage disorders depends on efficient
      uptake of recombinant enzyme into the tissues of patients. This uptake is
      mediated by oligosaccharide receptors including the cation-independent mannose 6
      phosphate receptor and the mannose receptor. We have sought to exploit
      alternative receptor systems that are independent of glycosylation but allow for
      efficient delivery to the lysosome. Fusions of the human lysosomal enzymes alpha
      l-iduronidase or acid alpha-glucosidase with the receptor-associated protein were
      efficiently endocytosed by lysosomal storage disorder patient fibroblasts, rat C6
      glioma cells, mouse C2C12 myoblasts, and recombinant Chinese hamster ovary cells
      expressing individual members of the low-density lipoprotein receptor family.
      Uptake of the fusions exceeded that of phosphorylated enzyme in all cases, often
      by an order of magnitude or greater. Uptake was specifically mediated by members
      of the low-density lipoprotein receptor protein family and was followed by
      delivery of the fusions to the lysosome. The advantages of the lipoprotein
      receptor system over oligosaccharide receptor systems include more efficient
      cellular delivery and the potential for transcytosis of ligands across tight
      endothelia, including the blood-brain barrier.

PMID- 15170392
TI  - High intensity exercise enhances platelet reactivity to shear stress and
      coagulation during and after exercise.
AB  - Platelets play a crucial role in the pathogenesis of acute cardiac events, such
      as angina, myocardial infarction and sudden death. It is believed that regular
      low-intensity exercise can reduce, while high-intensity exercise may provoke
      acute cardiac events. The aim of the present study was to investigate the effect
      of acute exercise both at low and high intensities on the ventilatory threshold
      (VT), platelet reactivity and coagulation before and after exercise. Platelet
      reactivity and coagulation were measured under flow condition, using native
      blood, by hemostatometry. Seven healthy young men (age: 20-29 years) performed
      bicycle ergometer exercise for 30 min at intensities of 90% (Ex-VT90% or
      approximately 55% VO(2max)) and 130% (Ex-VT130% or 80% VO(2max)) of individual
      VT. Blood cell counts, hematocrit, blood lactic acid and plasma catecholamine
      levels were slightly but significantly increased after Ex-VT90% and markedly
      after Ex-VT130% after 30 min exercise. Subsequent to the exercise, the elevated
      blood cell counts decreased to the resting levels both at Ex-VT90% and at Ex
      VT130%. Platelet reactivity to shear stress and dynamic coagulation were
      significantly enhanced immediately and 30 min after Ex-130%VT. In contrast, no
      significant changes occurred in those of Ex-90%VT. The present study suggests
      that high-intensity exercise-induced platelet hyperreactivity and hypercoagulable
      state may pose an increased risk for acute, sometimes fatal cardiac event. On the
      other hand, our findings support the view that low-intensity exercise does not
      present a risk of thrombosis.

PMID- 15170391
TI  - Influence of a long-term, high-dose volume therapy with 6% hydroxyethyl starch
      130/0.4 or crystalloid solution on hemodynamics, rheology and hemostasis in
      patients with acute ischemic stroke. Results of a randomized, placebo-controlled,
      double-blind study.
AB  - BACKGROUND: This study was performed to investigate the clinical effects of a 4
      day volume therapy with a newly developed, 6% hydroxyethyl starch (HES) 130/0.4
      versus crystalloid solution, with particular regard to systemic and cerebral
      hemodynamics, rheology and safety. METHODS: In a randomized, double-blind study,
      40 patients suffering from an acute ischemic stroke received either 6% HES
      130/0.4 or crystalloid solution as continuous infusion over 4 days with a total
      dose of 6.5 liters. Efficacy parameters studied included hemodynamics (cardiac
      output, blood pressure, flow velocity with transcranial Doppler) and rheology
      (hematocrit and plasma viscosity). Safety parameters examined included
      laboratory, hemostaseology (including factor VIII) and an adverse event
      questionnaire (including pruritus). RESULTS: In both groups, a small, but not
      significant increase in cardiac output was observed. There were no significant
      changes regarding the remaining efficacy or safety parameters, except for the
      well-known increase in serum alpha-amylase through the infusion of HES.
      CONCLUSION: In our study with patients suffering from acute ischemic stroke,
      continuous infusion (1 ml/min) of HES 130/0.4 or crystalloid solution did not
      differ regarding safety or hemodynamic efficacy.

PMID- 15170394
TI  - The effect of dietary bacillus natto productive protein on in vivo endogenous
      thrombolysis.
AB  - The influence of dietary bacillus natto productive protein (BNPP) on endogenous
      thrombolysis was investigated in the rat. Animals were given a standard feed for
      14 weeks, to which 0.2 or 1% BNPP was added. Thrombolysis was evaluated using an
      He-Ne laser-induced thrombosis model in mesenteric microvessels. Changes in
      thrombus volume, reflecting thrombolysis, decreased to 82% of the initial value
      in the control group. In contrast, the thrombus volume decreased to 67% in the
      animals fed 0.2% BNPP, and decreased to 51% in the group given 1% BNPP. The
      extent of thrombolysis in the 1% BNPP group was equivalent to that seen in
      animals treated with a bolus intravenous infusion of 0.2 mg/kg tissue plasminogen
      activator. The results demonstrated that the dietary administration of BNPP
      enhanced endogenous thrombolysis in a dose-dependent manner. Argatroban (2
      mg/kg/h) enhanced endogenous fibrinolysis only in control animals, but not in the
      BNPP groups. The results support the suggestion that dietary supplementation with
      BNPP may provide a simple means to promote fibrinolysis not only in the treatment
      of thromboembolism but also in the prevention of venous occlusion.

PMID- 15170395
TI  - Effects of surgical trauma and cardiopulmonary bypass on active thrombin
      concentrations and the rate of thrombin inhibition in vivo.
AB  - The in vivo concentration of active thrombin and the second-order rate constant
      for the inhibition of thrombin by antithrombin (k(inh)) were estimated in
      patients undergoing cardiopulmonary bypass (CPB) based on measured levels of
      hemostatic markers in combination with a computer model of the patient's
      hemostatic and vascular systems. At baseline k(inh) = 0.6 +/- 0.1 microM(-1) s(
      1) leaving 270 +/- 101 fM of active thrombin in the circulation. These factors
      were unchanged after sternotomy. Soon after heparin administration and the start
      of CPB, k(inh) increased 25-fold resulting in decreased active thrombin. After
      CPB and heparin neutralization, k(inh) decreased to 8-fold above baseline
      allowing active thrombin levels to rise. Both factors had returned to normal 2 h
      after surgery. We conclude that CPB with heparinization results in a rapid
      increase in thrombin inhibition leading to decreased active thrombin levels in
      vivo.

PMID- 15170393
TI  - Recurrent pregnancy loss and its relation to FV Leiden, FII G20210A and
      polymorphisms of plasminogen activator and plasminogen activator inhibitor.
AB  - Thrombophilic disorders and hypofibrinolysis were demonstrated to be risk factors
      in a majority of women with recurrent pregnancy loss (RPL) and infertility. We
      investigated the association of FV G1691A mutation, F II G20210A gene
      polymorphism (PM), 4G/5G PAI-1 and Alu I/D tPA PM in 32 women with infertility
      and 49 women with at least 2 unexplained early abortions. FV Leiden mutation was
      significantly more common in women with RPL (10%, p = 0.02) and infertility (19%,
      p = 0.0005) compared with controls (2%). PAI-1 4G PM and t-PA Alu I PM, alone or
      in combination, were not associated with RPL or infertility. 9/49 women with RPL
      showed coagulation disorders with heterozygous FV Leiden mutation (5), FXII (1),
      protein C (1) or protein S (2) deficiency. However, due to the small number of
      patients studied, no definite conclusion can be drawn.

PMID- 15170396
TI  - Factor V gene (1691A and 4070G) and prothrombin gene 20210A mutations in patients
      with Behcet's disease.
AB  - OBJECTIVES: Behcet's disease (BD) is a chronic inflammatory disorder of still
      unknown etiology, characterized by endothelial cell injury/dysfunction and
      thrombosis and/or aneurysm of large blood vessels. Thrombophilia may play a role
      in the pathogenesis of thrombosis in BD. The common inherited gene defects,
      factor V (FV) 1691A (Leiden) and prothrombin (PT) 20210A, are known risk factors
      for thrombosis. The FV 4070G polymorphism was shown to influence circulating FV
      levels and to contribute to the activated protein C resistance phenotype. The aim
      of the study was to evaluate the role of FV 1691A, FV 4070G and PT 20210A gene
      mutations in Turkish BD patients with and without venous thrombosis. METHODS:
      Seventy-one patients with BD (27 with venous thrombosis) and 91 healthy subjects
      were included in the study. FV 1691A, FV 4070G, and PT 20210A mutations were
      determined by a method based on PCR-RFLP. RESULTS: The frequency of FV 1691A
      heterozygous mutation in BD patients with venous thrombosis (25.9%) was
      significantly higher than that in healthy subjects (8.8%; OR = 3.63; 95% CI 1.18
      11.2). Although the frequency of this mutation in patients with venous thrombosis
      was higher than that in the patients without venous thrombosis (11.4%), the
      difference did not reach a statistically significant level (OR = 2.73; 95% CI
      0.77-9.70). In BD patients with thrombosis, the frequencies of FV 4070G and PT
      20210A were not significantly different compared to the BD patients without
      venous thrombosis and healthy subjects. CONCLUSIONS: Our results suggest that the
      FV 1691A, FV 4070G, and PT 20210A mutations are unlikely to play an important
      role in the pathogenesis of thrombosis in patients with BD.

PMID- 15170397
TI  - Fibrinogen polymorphisms TaqI, HaeIII and BclI are not associated with a higher
      risk of deep vein thrombosis.
AB  - High fibrinogen is recognised as a risk factor for atherosclerosis. It seems that
      high fibrinogen is also a risk factor for deep vein thrombosis (DVT). It has been
      shown that certain polymorphisms in fibrinogen genes can influence the fibrinogen
      level. In this study, fibrinogen levels and the frequency of the polymorphisms
      TaqI, HaeIII and BclI were studied in 114 patients with DVT and 244 healthy
      subjects. In non-smokers, fibrinogen levels above 5 g/l were associated with an
      increased risk of DVT (odds ratio 3.3, 95% confidence interval 1.6-7.0). The
      frequencies of common alleles were similar in patients and healthy subjects for
      all polymorphisms. An association between fibrinogen levels and the polymorphisms
      TaqI, HaeIII and BclI was found in healthy subjects, but not in the patients. It
      was concluded from these data that the polymorphisms TaqI, HaeIII and BclI are
      not major risk factors for DVT.

PMID- 15170398
TI  - Amniotic fluid embolism with haemostasis complications: primary fibrinogenolysis
      or disseminated intravascular coagulation?
AB  - Amniotic fluid embolism (AFE) is characterized by the passage of amniotic fluid
      (AF) into the maternal circulation during or just after childbirth. AFE is a rare
      disorder occurring in 1/8,000 to 1/80,000 deliveries but with a maternal
      morbidity ranging from 26% in a recent report to 86% in earlier ones. In patients
      who survive, AFE may affect coagulation resulting in severe bleeding. While
      disseminated intravascular coagulation (DIC) is usually seen in such cases, we
      reported a case of AFE in which the hemostatic abnormalities were compatible with
      primary fibrinogenolysis rather than with DIC.

PMID- 15170399
TI  - Self-assembly and type III protein export of the bacterial flagellum.
AB  - The bacterial flagellum is a supramolecular structure consisting of a basal body,
      a hook and a filament. Most of the flagellar components are translocated across
      the cytoplasmic membrane by the flagellar type III protein export apparatus in
      the vicinity of the flagellar base, diffuse down the narrow channel through the
      nascent structure and self-assemble at its distal end with the help of a cap
      structure. Flagellar proteins synthesized in the cytoplasm are targeted to the
      export apparatus with the help of flagellum-specific chaperones and pushed into
      the channel by an ATPase, whose activity is controlled by its regulator to enable
      the energy of ATP hydrolysis to be efficiently coupled to the translocation
      reaction. The export apparatus switches its substrate specificity by monitoring
      the state of flagellar assembly in the cell exterior, allowing this huge and
      complex macromolecular assembly to be built efficiently by a highly ordered and
      well-regulated assembly process.

PMID- 15170400
TI  - Dual flagellar systems enable motility under different circumstances.
AB  - Flagella are extremely effective organelles of locomotion used by a variety of
      bacteria and archaea. Some bacteria, including Aeromonas, Azospirillum,
      Rhodospirillum, and Vibrio species, possess dual flagellar systems that are
      suited for movement under different circumstances. Swimming in liquid is promoted
      by a single polar flagellum. Swarming over surfaces or in viscous environments is
      enabled by the production of numerous peritrichous, or lateral, flagella. The
      polar flagellum is produced continuously, while the lateral flagella are produced
      under conditions that disable polar flagellar function. Thus at times, two types
      of flagellar organelles are assembled simultaneously. This review focuses on the
      polar and lateral flagellar systems of Vibrio parahaemolyticus. Approximately 50
      polar and 40 lateral flagellar genes have been identified encoding distinct
      structural, motor, export/assembly, and regulatory elements. The sodium motive
      force drives polar flagellar rotation, and the proton motive force powers lateral
      translocation. Polar genes are found exclusively on the large chromosome, and
      lateral genes reside entirely on the small chromosome of the organism. The timing
      of gene expression corresponds to the temporal demand for components during
      assembly of the organelle: RpoN and lateral- and polar-specific sigma(54)
      dependent transcription factors control early/intermediate gene transcription;
      lateral- and polar-specific sigma(28) factors direct late flagellar gene
      expression. Although a different gene set encodes each flagellar system, the
      constituents of a central navigation system (i.e., chemotaxis signal
      transduction) are shared.

PMID- 15170401
TI  - The periplasmic flagellum of spirochetes.
AB  - Although spirochete periplasmic flagella have many features similar to typical
      bacterial flagella, they are unique in their structure and internal periplasmic
      location. This location provides advantages for pathogenic spirochetes to enter
      and to adapt in the appropriate host, and to penetrate through matrices that
      inhibit the motility of most other bacteria. These flagella are complex, and they
      dynamically interact with the spirochete cell cylinder in novel ways. Electron
      microscopy, tomography and three-dimensional reconstructions have provided new
      insights into flagellar structure and its relationship to the spirochetal cell
      cylinder. Recent advances in genetic methods have begun to shed light on the
      composition of the spirochete flagellum, and on the regulation of its synthesis.
      Because spirochetes have a high length to width ratio, their cells provide an
      opportunity to study two important features. These include the polarity or
      distribution of flagellar synthesis as well as the mechanisms required for
      coordination of the movement of the cell ends, to enable it to move in the
      forward or reverse direction.

PMID- 15170402
TI  - Recent advances in the structure and assembly of the archaeal flagellum.
AB  - Archaeal motility occurs through the rotation of flagella that are distinct from
      the flagella found on bacteria. The differences between the two structures
      include the multi-flagellin nature of the archaeal filament, the widespread
      posttranslational modification of the flagellins and the presence of a short
      signal peptide on each flagellin that is cleaved by a specific signal peptidase
      prior to the incorporation of the mature flagellin into the flagellar filament.
      Research has revealed similarities between the archaeal flagellum and the type IV
      pilus, including the presence of similar unusual signal peptides on the
      flagellins and pilins, similarities in the amino acid sequences of the major
      structural proteins themselves, as well as similarities between potential
      assembly and processing components. The recent suggestion that type IV pili are
      part of a family of cell surface complexes, coupled with the similarities between
      type IV pili and archaeal flagella, raise questions about the evolution of these
      systems and possible inclusion of archaeal flagella into this surface complex
      family.

PMID- 15170403
TI  - Pulling together with type IV pili.
AB  - Type IV pili are an efficient and versatile device for bacterial surface
      motility. They are widespread among the beta-, gamma-, and delta-proteobacteria
      and the cyanobacteria. Within that diversity, there is a core of conserved
      proteins that includes the pilin (PilA), the motors PilB and PilT, and various
      components of pilus biogenesis and assembly, PilC, PilD, PilM, PilN, PilO, PilP,
      and PilQ. Progress has been made in understanding the motor and the secretory
      functions. PilT is a motor protein that catalyzes pilus retraction; PilB may play
      a similar role in pilus extension. Type IV pili are multifunctional complexes
      that can act as bacterial virulence factors because pilus-based motility is used
      to spread pathogens over the surface of a tissue, or to build multicellular
      structures such as biofilms and fruiting bodies.

PMID- 15170404
TI  - Cytophaga-flavobacterium gliding motility.
AB  - Flavobacterium johnsoniae, like many other members of the Cytophaga
      Flavobacterium-Bacteroides group, displays rapid gliding motility. Cells of F.
      johnsoniae glide over surfaces at rates of up to 10 microm/s. Latex spheres added
      to F. johnsoniae bind to and are rapidly propelled along cells, suggesting that
      adhesive molecules move laterally along the cell surface during gliding. Genetic
      analyses have identified a number of gld genes that are required for gliding.
      Three Gld proteins are thought to be components of an ATP-binding-cassette
      transporter. Five other Gld proteins are lipoproteins that localize to the
      cytoplasmic membrane or outer membrane. Disruption of gld genes results not only
      in loss of motility, but also in resistance to bacteriophages that infect wild
      type cells, and loss of the ability to digest the insoluble polysaccharide
      chitin. Two models that attempt to incorporate the available data to explain the
      mechanism of F. johnsoniae gliding are presented.

PMID- 15170405
TI  - The junctional pore complex and the propulsion of bacterial cells.
AB  - Gliding motility is defined as translocation in the direction of the long axis of
      the bacterium while in contact with a surface. This definition leaves unspecified
      any mechanism and, indeed, it appears that there is more than one physiological
      system underlying the same type of motion. Currently, two distinct mechanisms
      have been discovered in myxobacteria. One requires the extension, attachment, and
      retraction of type IV pili to pull the cell forwards. Recent experimental
      evidence suggests that a second mechanism for gliding motility involves the
      extrusion of slime from an organelle called the 'junctional pore complex'. This
      review discusses the role of slime extrusion and the junctional pore complex in
      the gliding motility of both cyanobacteria and myxobacteria.

PMID- 15170406
TI  - Shaping and moving a spiroplasma.
AB  - The Mollicutes (Spiroplasma, Mycoplasma and Acholeplasma) are the most minimal
      cells known to exist, being the smallest and simplest free-living and self
      replicating forms of life. Phylogenetically, the Mollicutes are related to gram
      positive bacteria and have evolved, by regressive evolution and genome reduction,
      from Clostridia. The smallest genome in this group (Mycoplasma genitalium - 5.77
      x 10(5) bp) is only twice that of a large virus (e.g., Entomopox viruses). The
      largest Mollicute genome (Spiroplasma LB12 - 2.2 x 10(6) bp) is only about half
      that of, e.g., Escherichia coli. Structurally, the Mollicutes lack cell walls and
      flagella, but have internal cytoskeletons and are motile and chemotactic. Only a
      cholesterol-containing unit membrane envelops the cells. No analogs to the
      bacterial chemotactic and motility (che, mot, fla) genes, genes for a two
      component signal transduction system, genes associated with gliding, or genomic
      homologs for the eukaryotic cytoskeleton and motor proteins were found in the
      Mollicutes. The Spiroplasmas are unique amongst the Mollicutes in having a well
      defined basic helical cell geometry. In this respect, the Spiroplasma cell can,
      essentially, be viewed as a helical dynamic membranal tube (diameter
      approximately 0.2 microm; equivalent to that of one eukaryotic flagellar axoneme
      or to a bacterial flagellar bundle). A flat cytoskeletal ribbon of parallel
      fibrils is attached to the inside of the cellular tube. Both tube and
      cytoskeleton are mutually coiled into a dynamic helix driven by differential
      length changes of the fibrils, which function as linear motors. The cytoskeletal
      ribbon follows the shortest (inner) helical line on the inner surface of the
      cellular tube. Being helical allows for further analytical reduction and
      consequent structural quantification of Spiroplasma. Of particular importance is
      the ability to correlate light and electron microscopy data and to calculate the
      fibril lengths (and corresponding molecular dimensions) in the helical and
      nonhelical dynamic states. The structural unit of the contractile cytoskeleton is
      a approximately 50-Angstrom-wide filament comprised of pairs of the 59-kD fib
      gene product. The monomers are arranged in pairs with opposite polarities
      allowing for a approximately 100-Angstrom-long axial repeat. The functional unit
      of the contractile cytoskeletal ribbon is a fibril comprised of an aligned pair
      of filaments. Neighboring repeats form a tetrameric ring with a lateral repeat of
      approximately 100 A. The axial length of the rings may shorten by approximately
      40%, driving the changes in the fibril lengths and, consequently, helical
      dynamics. Local length changes result in helical symmetry breaking and
      nonreciprocating cell movements allowing for net directional displacement.
      Flexing allows for changes in swimming direction.

PMID- 15170407
TI  - Structure and function of beta3-adrenergic receptors.
AB  - Beta-adrenergic receptors have been subdivided into three types: beta1-, beta2-
      and beta3-adrenergic receptors. beta1-adrenergic receptors are predominant in the
      heart, beta2-adrenergic receptors--in the respiratory system, and beta3
      adrenergic receptors--in the adipose tissues. However, since 1989, when beta3
      adrenergic receptor was cloned, numerous biochemical and functional studies have
      confirmed its presence in various species and tissues, including the heart.
      Unlike beta1- and beta2-adrenergic receptors, it has been shown that beta3
      adrenergic receptors possess the cardiodepressant effects in human ventricles,
      what did not fit to its stimulatory properties of adenylyl cyclase in other
      tissues. In this regard, the role of beta3-adrenergic receptors in the regulation
      of cardiac function may be of great importance in pathological conditions and
      remains undetermined, so far. In this review brief characterization of beta3
      adrenergic receptors, concerning their structure, function and possible
      pathophysiological role is provided.

PMID- 15170409
TI  - [Proinflammatory cytokine interleukin-17 and its role in pathogenesis of
      rheumatoid arthritis].
AB  - This is a review concerning the role of interleukin-17, a proinflammatory
      cytokine, produced by activated memory CD4+ T cells, in pathogenesis of
      rheumatoid arthritis. As interleukin-17 shares properties with IL-1 and TNF
      alpha, it may induce joint inflammation and bone and cartilage destruction. This
      cytokine is found in synovial fluids of patients with rheumatoid arthritis, and
      produced by rheumatoid arthritis synovium. It increases IL-6 production, induces
      collagen degradation and decreases collagen synthesis by synovium and cartilage
      and proteoglycan synthesis in cartilage. Interleukin-17 is also able to increase
      bone destruction and reduce its formation. Blocking of interleukin-17 with
      specific inhibitors provides a protective inhibition of cartilage and bone
      degradation.

PMID- 15170408
TI  - [Poststreptococcal reactive arthritis].
AB  - Arthritis, following infection caused by group A beta-hemolytic streptococcus, is
      classically attributed to acute rheumatic fever. However, a new clinical
      syndrome, called poststreptococcal reactive arthritis, as a distinct entity from
      acute rheumatic fever, was described recently. The purpose of this paper is to
      provide a summary of published information on poststreptococcal reactive
      arthritis. The paper outlines its clinical description and proposed diagnostic
      criteria. Similarities and differences between poststreptococcal reactive
      arthritis and acute rheumatic fever are discussed. Information regarding long
      term risk of carditis following poststreptococcal reactive arthritis is provided,
      and therapeutic recommendations are outlined.

PMID- 15170410
TI  - The influence of antegrade scrotal sclerotherapy on the diameter of the spermatic
      cord veins in men with varicocele.
AB  - OBJECTIVE: To assess the influence of antegrade scrotal sclerotherapy on diameter
      of veins of the pampiniform plexus of the spermatic cord by comparison of the
      vein diameter before and after the operation in patients with varicocele; to
      evaluate the rate of recurrence of the disorder after antegrade scrotal
      sclerotherapy and significance of color Doppler ultrasonography in the diagnosis
      of varicocele; and to estimate the efficacy of the treatment. MATERIAL AND
      METHODS: Forty-one patients with various degrees of varicocele treated by
      antegrade scrotal sclerotherapy were included in the study. The size of the
      pampiniform plexus of veins of the patients was evaluated clinically during
      physical examination, and its diameter was measured by color Doppler
      ultrasonography before and after the operation in the upright and the supine
      positions during the Valsalva maneuver and without it. RESULTS: After antegrade
      scrotal sclerotherapy, the diameter of the studied veins was found reliably
      decreased while examined in all four patient's examining positions, independently
      of the degree of the preoperative varicocele and recurrence of the disorder. The
      postoperative decrease of diameter of veins was inversely proportional to the
      degree of varicocele, i. e. the diameter of veins in the third degree varicocele
      became most reduced. The recurrence of varicocele after antegrade scrotal
      sclerotherapy was revealed in 21.9% of the operated patients. The diameter of
      veins in the recurrent varicocele, assessed by physical examination, and venous
      blood reflux, detected by ultrasound, reliably decreased in the upright position
      of patients (p<0.005), whereas in the supine position, diameter of the studied
      veins remained almost the same as it was before the operation (p=0.9).
      CONCLUSIONS: After antegrade scrotal sclerotherapy, the diameter of the
      varicocele vein decrease was statistically significant. It was mostly expressed
      after the operation in the cases of the third degree varicocele. The
      postoperative diameter of veins in the recurrent varicocele of the examined
      patients in the upright position was also reliably smaller than before the
      operation, but it practically did not differ from the preoperative diameter when
      the patients were examined in the supine position.

PMID- 15170412
TI  - [The efficiency of home and outpatient exercise program in patients with
      rheumatoid arthritis].
AB  - OBJECTIVE: To compare the efficiency of home and outpatient exercise program in
      patients with rheumatoid arthritis. METHODS: Patients with rheumatoid arthritis
      were randomly assigned to home exercise program group and outpatient exercise
      program group. Variables of muscle and hand strength, joint mobility, visual
      analog scale of pain were assessed before and after the 3 months exercise course.
      RESULTS: Out of 43 patients, 31 completed the study. Both groups improved in
      measures of muscle strength, joint mobility and pain. Differences between groups
      were statistically significant for measures of grip strength in the home exercise
      group (p=0.0001), and joint mobility--in the outpatient exercise group (p=0.047).
      CONCLUSIONS: Exercise program was more effective in improving grip strength in
      the home exercise program group and joint mobility improved more in the
      outpatient exercise group.

PMID- 15170411
TI  - Treatment of the leg ulcers by skin grafting.
AB  - The ulcers, located below the knees and remaining for 6 weeks and more, are
      called trophic leg ulcers. The leg ulcers of different etiology disable 0.8-1% of
      total Earth population. It was found that blood vessel problems in legs account
      for more than 80% of ulcers; even 65% from these are caused by venous diseases.
      In Lithuania about 8000 patients suffer from venous trophic ulcers. Regardless of
      modern methods the treatment of leg ulcers remains an extremely expensive
      process. The treatment cost of trophic ulcers is the highest of all surgical
      wounds and also requires a lot of personal investments. In order to assess the
      efficiency of autodermoplastics in the treatment of large venous ulcers in legs a
      prospective study was carried out of 111 patients who were treated in the
      Department of Plastic Surgery and Burns of Kaunas University of Medicine Hospital
      from January 2001 to January 2004. The data was analyzed exceptionally of the
      operated 54 patients with venous origin ulcers open for more 6 months or
      exceeding 50 cm2. The above-mentioned patients were prepared for surgery by
      dressing the wounds with hydrocolloid Granuflex bandages and were operated by
      transplanting a 0.2-0.3 mm thick skin graft. The results were estimated by the
      surgeon during the dressings after the operation. The graft was taken in 35
      (64.81%) cases; in 19 (35.19%) cases the graft was partially not taken and there
      were no cases when it was not taken at all. We came to the conclusions that skin
      graft transplantation is efficient in treatment of trophic venous leg ulcers
      larger than 50 cm2 and cures the trophic leg ulcers of vein origin completely in
      2-3 weeks for 64.81% patients.

PMID- 15170414
TI  - [Peculiarities of stereovision in children].
AB  - OBJECTIVE: The aim of this work was to evaluate the stereovision and the
      stereoacuity of the preschool children and to compare various stereotests.
      MATERIAL AND METHODS: The test group consisted of 118 children who were divided
      into 3 age groups: 2-3 year-old group (22.03%), 4-5 year-old group (43.22%) and 6
      7 year-old group (34.75%). Titmus, Lang I and contour anaglyphic pictures
      stereotests were used. RESULTS: The stereovision was investigated in 94.92% of
      children (88.46% in 2-3 year old group, 96.08% in 4-5 years and 97.56% in 6-7
      year-old group). The stereoacuity of 40" was detected in 63.41% of 6-7 year-old
      and only in 7.69% of 2-3 year-old children. CONCLUSIONS: A reverse correlation
      was noticed between the stereoacuity and the frequency of positive results in all
      age groups. The frequency of positive stereovision in various disparity levels
      and the stereoacuity increase together with the age of children; these data were
      significant between the groups of 2-3 years and 6-7 years (p<0.05). Data did not
      show significant differences between various stereotests, but we noticed that
      contoured stereotests were more comprehensible to the 2-5 year-old children.

PMID- 15170413
TI  - [Comparison of clinical performance of troponin T and troponin I in diagnosing
      acute myocardial infarction].
AB  - In this article we investigate clinical specificity and sensitivity of cardiac
      troponin T and cardiac troponin I tests in the patients who were admitted to the
      hospital with suspected acute coronary syndrome. We investigated 87 patients: the
      clinical investigation was performed, electrocardiogram was recorded and
      concentrations of cardiac troponin T and troponin I were estimated. According to
      the recommendations of the manufacturers of troponin T and troponin I tests,
      threshold diagnostic troponin T concentration for myocardial infarction was
      considered > or =0.1 ng/ml and troponin I > or =1.0 ng/ml. Troponin T
      concentration was analyzed in 60 patients; the sensitivity of troponin T test in
      diagnosing acute myocardial infarction was 85%, and the specificity was 87.2%.
      Troponin I test was performed in 46 patients; the sensitivity of the test was 76%
      and the specificity was 76.2%. In case when both troponin T and I tests were
      performed, the sensitivity of troponin T was 100% and specificity was 78% and of
      troponin I - respectively 86% and 78%. According to the receiver operator
      characteristic analysis there was no significant difference between the general
      accuracy of troponin T and troponin I in distinguishing patients with and without
      acute myocardial infarction. According to the results of receiver operator
      characteristic analysis, the biggest clinical sensitivity and specificity were
      achieved when threshold myocardial infraction diagnostic concentration of
      troponin T was considered >0.04 ng/ml and of troponin I >0.69 ng/ml.

PMID- 15170415
TI  - The influence of aerobics exercise to cardiovascular functional parameters of 30
      40 year old women.
AB  - The aim of this study was to evaluate the cardiovascular functional parameter
      changes for 30-40 year old women following the aerobics exercise program. The
      material consisted of 14 women, who participated in aerobics exercise 3 times per
      week (the average age 33.71+/-1.28 years). The following methods were used in
      this work: arterial blood pressure measuring, electrocardiogram analysis and
      bicycle ergometry work. System of ECG analysis "Kaunas-Kruvis" was used for the
      monitoring of cardiovascular system reactions. 12 ECG standard derivations were
      synchronically recorded. Physical work method of provocative incremental bicycle
      ergometry exercise was used. The bicycle ergometry work was performed applying 50
      W intensity in the beginning and increasing the power every minute by 25 W. The
      following functional parameters were estimated in this study: heart rate,
      arterial blood pressure, JT interval, ST segment depression at rest and in each
      level of functional load. RESULTS: It was established that heart beat rate of
      participants statistically significantly decreased (p<0.05) at rest and in each
      level of functional load after one year of regular aerobics exercise. Although JT
      interval values of participating women were higher during the second examination
      than during the first one, only in one level of functional load (at 75 W power)
      there was statistically significant (p<0.05) increase of this parameter.
      Statistically significant decrease (p<0.05) at 50 W and 75 W intensity of ST
      segment depression was observed in the examination. The systolic blood pressure
      of women, who were engaged in the aerobics exercise, did not change; the
      diastolic blood pressure statistically significantly decreased (p<0.05), when
      participant achieved 75 W and 100 W intensity. CONCLUSION: Aerobics exercise is
      the proper physical activity form for 30-40 year old women for the developing of
      cardiovascular functional parameters.

PMID- 15170416
TI  - Expression of progesterone receptors in bovine corpus luteum during pregnancy.
AB  - The expression of progesterone receptors and matrix ribonucleic acid in 37
      corpora lutea in 1-7 month's pregnant cows was investigated. Corpora lutea were
      obtained from slaughtered animals. Progesterone receptors expression was
      confirmed using biotin-streptavidin immunohistochemistry. Matrix ribonucleic acid
      expression was studied using pyronin staining by Unna-Brashe method. The
      expression of progesterone receptors was the highest in the luteal cells of the
      one-month pregnancy corpus luteum. It decreased significantly (p<0.05) from the
      third to the fourth month of pregnancy, but there was no significant difference
      in the expression of progesterone receptors from the first to the second and from
      the second to the third month of pregnancy. Also, there was no significant
      difference in the expression of progesterone receptors from the fourth to the
      fifth month and from the fifth to the sixth month of pregnancy. The expression of
      matrix ribonucleic acid also decreased during pregnancy, but gradually, with no
      significant monthly differences. It decreased significantly (p<0.05) from the
      sixth to the seventh month of pregnancy only. Our study shows that both indices -
      progesterone receptors and matrix ribonucleic acid decrease in the steroidogenic
      luteal cells during pregnancy and that a strong linear correlation (r=0.88)
      exists between these indices.

PMID- 15170417
TI  - [Influence of patient's social and demographic characteristics on patient's
      expectations for medical consultation].
AB  - Most of the patients, coming to see their primary care physician, have explicit
      expectations and priorities for the medical consultation. Recognition of these
      expectations is an important step in organizing patient-oriented health care
      services. Patient expectations depend on a number of factors: health problem and
      its severity, as well as social and demographic characteristics of patient and
      physician. Objective of this survey was to evaluate influence of patient's socio
      demographic characteristics and some health status indicators on expectations for
      primary care consultation. MATERIAL AND METHODS: During the study 403 patients
      and 162 physicians were surveyed. Pre-visit expectations of patients coming to
      see their primary care physician for health problem were investigated using self
      addressed original questionnaire. RESULTS: Factor analysis revealed three main
      factors: biomedical expectations, emotional support expectations and expectations
      for partnership. Analysis of influence of socio-demographic characteristics on
      patient expectations showed that statistically significant differences in
      different age groups were found only for emotional support factor. Patients'
      desire for emotional support from doctor increased with age. Relationship was
      observed between expectations for emotional support and health status as
      perceived by patient. Patients evaluating their health problem as not serious had
      mean score of expectations for emotional support 3.4, patients with moderate
      health problem--3.5, patients with serious health problem--4.0 out of 5.
      CONCLUSIONS: Patient's need for emotional support from physician depends on his
      age, marital status, frequency of his visits to physician during the year, self
      perception of the health status and course of disease. Analysis of relationship
      between patient's expectations and his sex, education, physician's sex or type of
      practice did not show statistically significant differences between groups. No
      influence of analyzed social and demographic characteristics or perceived health
      status on biomedical expectations (laboratory tests, specialist consultations,
      and hospital treatment) was found during our study.

PMID- 15170418
TI  - Maternal socio-economic factors and the risk of low birth weight in Lithuania.
AB  - AIM: To evaluate the importance of maternal socio-economic factors on the risk of
      low birth weight in Lithuania. MATERIAL AND METHODS: The case-control study
      involved 851 newborns with low birth weight (<2500 g) (cases) and 851 newborns
      with normal weight (controls). Study was accomplished from 1st February, 2001
      until 31st October, 2002 in six main maternity hospitals in Lithuania. Mothers of
      infants were interviewed on the first day after delivery using the structured
      questionnaire. The database was processed by the application of statistical
      package "SPSS for Windows v.10.0". RESULTS: Young (<20 years) and older (35 years
      and older) maternal age, primary or basic education, being single, divorced or
      widowed, low income, living in rural area and unemployment before pregnancy and
      during pregnancy increased the risk to deliver low birth weight baby in
      univariate analysis. In logistic multivariable regression analysis, low
      education, low income and unemployment during pregnancy significantly increased
      risk of low birth weight--OR - 2.0, 1.7 and 1.6 respectively. Interaction between
      several unfavorable risk factors increased risk of low birth weight by 3.4-7.8
      times, being the highest among mothers with low education, unstable marital
      status and low income. CONCLUSION: Maternal unfavorable socio-economic factors
      increased the risk to deliver low birth weight baby.

PMID- 15170419
TI  - [Fifty years of creative work (Society of Lithuanian Pathologists, 1954-2004)].
AB  - The article deals with the activity stages and forms of Society of Lithuanian
      Pathologists (in 1954-1991--Republic Scientific Society of Pathologoanatomists,
      in 1991-1996--Society of Lithuanian Pathologoanatomists). Founder of the Society
      and the first President (in 1954-1976) was prof. Janina Mackevicaite-Lasiene, in
      1976-1996--prof. Elena Stalioraityte and since 1996 up till now--prof. Dalia
      Pangonyte. Taking into account the needs of medical research and practice, its
      activities varied. According to the tasks there are 4 stages of Society activity.
      The first--establishment of pathological practice, introduction into clinic and
      pathological practice of pathogenetic and nosologic diagnosis; the second-
      consolidation and development of pathological practice, conveyance of pathology
      knowledge, optimization of pathology teaching and training of specialists; the
      third--reforming of Society and pathological practice, widening of international
      relations; the fourth--introduction of recent methods and information
      technologies in pathological practice and teaching. The Society has organized ten
      republic conference and two congresses, four school-seminars, its members
      published 19 monographs and collections of articles, 6 textbooks, 28 learning
      books, 26 methodical recommendations, more than fifty members acquired academic
      degree.

PMID- 15170420
TI  - [Multiple endocrine neoplasia syndroms. Type 1].
AB  - Multiple endocrine neoplasia (MEN) type 1 syndrome or Wermer syndrome is a
      classical malignant neoplasia syndrome, inherited in the autosomal dominant
      pattern, when hyperplastic and/or neoplastic injury develops synchronously or
      metachronously in the cells of the parathyroid gland, pancreas islets,
      hypophysis, and rarer in other neuroendocrine organs. The syndrome develops when
      germinative MEN 1--neoplasia suppression gene inactivation mutations occurs. More
      than 95 percent of patients have this MEN 1 gene mutation, when the penetration
      of mutation is almost 100 percent. An early stage of this syndrome is
      hyperfunction in organs, with the syndromes of hormone excess, later benign
      and/or malign neoplasia develops, this mostly determines the prognosis for the
      patient. The risk of this syndrome developing should be estimated for all the
      patients diagnosed with endocrine organ hyperplasia, which determines
      hyperfunction, or endocrine organs neoplasia. For patients with multiple
      endocrine neoplasia type 1 syndrome, endocrine neoplasia develops earlier than in
      sporadic cases; multifocality is typical for them. Multifocality of neoplasia,
      typical combinations of injuries and anamnesis of the family helps to diagnose
      the syndrome. Diagnosis is confirmed through genetical analysis, which is also
      important in determining the inheritors of mutations, potential patients. After
      genetically diagnosing multiple endocrine neoplasia type 1 syndrome, it is not
      enough to analyze and look after patients with malignant neoplasia, or to make
      early diagnosis on pre-neoplasic disease and neoplasia, or to apply means of
      prevention and start well-timed treatment, but also to diagnose this syndrome for
      the patient's relatives, and to determine their risk of getting cancer. This
      opens new possibilities in early diagnostics and prevention of malignant
      neoplasia. The main purpose of this literature review is to introduce medical
      practitioners to the newest theories of type 1 multiple endocrine neoplasia
      syndrome pathogenesis, clinical peculiarities, methods of diagnostics and
      treatment.

PMID- 15170422
TI  - [A certain analysis of the literature as the only modern approach to deciding on
      delivery route: a progress for women].

PMID- 15170423
TI  - [Evaluation of cesarean rate: a necessary progress in modern obstetrics].
AB  - During the last 10 Years, the cesarean section (CS) rate was increased despite of
      the recommendations of the World Health Organization to keep it below 10-15%. The
      purpose of this review of the literature was to demonstrate how the concept of CS
      rate limitation has become obsolete. The increase in the CS rate is mainly
      justified by the decrease in maternal mortality and morbidity following elective
      CS: surgery-related risks have decreased and the confusion that was made between
      the risks of vaginal delivery and those of trial of labor has to be clarified to
      show that maternal mortality and morbidity are not increased by elective CS.
      However, instrumental delivery and CS during labor remain two situations at high
      risks both for the mother and her fetus. There is also an association between the
      increase in the CS rate and the decrease in perinatal mortality and morbidity,
      but this effect would only become clinically significant after a dramatic
      increase in the CS rate: this is the preventile principle of "marginal death".
      Numerous articles have been published reporting on the effects of vaginal
      delivery for the pelvic floor: urinary incontinence, pelvic organ prolapse, and
      especially fecal incontinence. All these publications concluded that CS has a
      protective effect. The rising duty to provide information to patients in high
      risk obstetrical situations such as a history of CS also contributes to the
      overall increase in CS rate mainly through the elective CS rate. Indeed, when
      faced with the alternative choices of potentially severe complications either for
      themselves or their child, women are likely to choose what appears to be the
      safest mode of delivery for their child and thus to opt for a CS. Finally,
      widespread delivery of information to the patients about trial of labor itself
      and the risks of vaginal delivery is the first step towards a "principle of
      preference", which consists in giving an important place to the patient's choice
      in the decision-making process, and thus to recognize her right to ask for an
      elective CS.

PMID- 15170424
TI  - [An update on the fetal circulation].
AB  - The fetal circulation has been an exciting area of study for centuries. The
      principles which grew from the period of hypotheses have been demonstrated in
      several animal models. These experiments have shaped the major concept of fetal
      circulation. More recently, the improvement in ultrasound technology has allowed
      a non invasive study of the fetal circulation in humans. Although the general
      schema of the fetal circulation has been confirmed in humans, in some aspects
      some substantial differences have been demonstrated. They may not only reflect
      some inter-species differences, but also underscore the limitation of chronically
      instrumented animal studies.

PMID- 15170425
TI  - [External cephalic version: experience about 237 versions at Port-Royal
      maternity].
AB  - OBJECTIVES: To evaluate the effectiveness of external cephalic version for
      reducing the rate of cesarean section by preserving fetal safety. MATERIALS AND
      METHODS: A retrospective review of 237 external cephalic versions between January
      1, 1998 and December 31, 2000 was conducted at Port Royal maternity. RESULTS: The
      success rate of external cephalic version was 50.6%. When version failed vaginal
      birth could be allowed after strict evaluation. The rate of cesarean section was
      12.5% in the success group and 53% in the unsuccessful group, two thirds were
      planned. The overall rate of vaginal birth among breech presentations was 67%.
      After version there were 3.4% abnormal fetal heart rate tracings and 2.9%
      positive Kleihauer tests. No major complications occurred. Successful external
      cephalic version was associated with statistically significant higher
      multiparity, complete breech out of the pelvis and normal amniotic fluid Volume.
      CONCLUSION: External cephalic version reduces the cesarean section rate by about
      20.5% among breech presentations and so, lowers maternal morbidity. External
      cephalic version could be proposed to the patients when safety criteria are
      respected and close fetal monitoring is maintained.

PMID- 15170426
TI  - [Complications of vacuum extractor deliveries].
AB  - OBJECTIVES: To describe maternal and neonatal complications following deliveries
      assisted by vacuum extraction and to compare outcomes with those obtained after
      spontaneous vaginal delivery. We wanted to know if vacuum extractor was a risk
      factor by itself. MATERIALS AND METHODS: We conducted a retrospective study of
      two years activity involving 4524 deliveries of which 845 (18.7%) were vacuum
      extractor assisted. We precisely defined maternal and neonatal complications to
      compare their rates in spontaneous vaginal delivery and vacuum extractor groups.
      RESULTS: There were 1333 maternal complications and 114 neonatal complications.
      The adjusted risks of maternal complications were significantly higher in the
      vacuum extractor group for simple vaginal tears (OR=3.0; p<0.001), the simple
      perineal tears (OR=1.8; p<0.001) and third degree perineal tears (OR=2.7;
      p<0.01). For neonatal complications, the difference was significant for
      cephalhematomas (OR=10; p<0.001) and scalp abrasions (OR=53; p<0.001). No cases
      of skull fracture or subgaleal subaponeurotic hemorrhage were recorded.
      CONCLUSION: Our rates of maternal and neonatal complications after vacuum
      extractor were similar to those described in the literature. We have been able to
      show that vacuum extraction is itself a risk factor for third degree perineal
      tears and cephalhematoma. However, these complications are so infrequent that the
      advantages of this method of extraction argue in favor of wide use in obstetrics.

PMID- 15170427
TI  - [Trial of labor in moderate pelvic dystocia at Dakar University Teaching
      Hospital].
AB  - OBJECTIVE: To study frequency of moderate pelvic dystocia, to evaluate the
      diagnosis value of clinical pelvic evaluation and prognosis of trial labor with
      only clinical monitoring. MATERIAL AND METHOD: This is a prospective, exposed and
      non-exposed study concerning 296 women selected among deliveries presenting
      moderate pelvic dystocia recorded at Dakar University Teaching Hospital from
      February 1st 2001 to July 31 2002. Trial labor was undertaken in 148 patients;
      the control group was chosen among women who underwent prophylactic caesarean
      section and had no other risk factors of maternal and perinatal complications.
      Pearson's chi-square test was used or statistic analysis with p value 5% and test
      of Kappa. RESULTS: Moderate pelvic dystocia was observed 5.3 per 100 deliveries.
      The most common epidemiological profile was primipara, young age (mean 24 years),
      height 161 cm (mean), 38-week pregnancy (mean). Clinical evaluation had good
      diagnosis value comparable with the radiological pelvimetry. Trial labor was
      undertaken in 148 women, 109 trials (73.6%) were successful; vaginal delivery
      rate was 27% in women with moderate pelvic dystocia. There were no maternal
      deaths, maternal morbidity was 4% in trial labor patients and 2.7% in
      prophylactic caesarean section patents (mainly infection). Post-natal mortality
      was 7.4% after trial of labour versus 4.1% of newborn child after prophylactic
      caesarean. CONCLUSION: These results confirm that trial of labor on moderate
      pelvic dystocia should be the rule whenever possible, even when only clinical
      monitoring is available.

PMID- 15170428
TI  - [Laparoscopic management of adnexal tumors after the first trimester of
      pregnancy].
AB  - PURPOSE OF THE STUDY: To study the feasibility, advantages and risks of
      laparoscopic management of adnexal tumors in the course of the last two
      trimesters of the pregnancy. MATERIAL AND METHODS: Retrospective study of a
      series of 25 cases of adnexal tumors operated by laparoscopy in the course of the
      second and the third trimester of pregnancy, during a period of 49 Months from
      1st January 1999 to 30 January 2003. RESULTS: Mean gestational age at surgery was
      16 weeks 3 days (range 12-29 weeks). The adnexal tumor was an ovarian cyst in 24
      cases and in a paratubal cyst in a single case. Conversion was necessary in only
      one case due to difficult hemostasis. One revision required for borderline
      malignancy cystadenoma was performed laparoscopically during the same pregnancy.
      No operative complication was noted. Average post-operative stay was 36 hours
      (range 24-72 hours). There was one situation of eminent abortion in early the
      postoperative period but no thromboembolic complications. The pregnancy progress
      was normal after laparoscopy. CONCLUSION: Laparoscopic treatment of adnexal
      tumors is feasible in the course of the last two trimesters of the pregnancy in
      the hands of an experienced surgeon using advanced techniques. The well-known
      advantages of laparoscopy are particularly important during the pregnancy.

PMID- 15170429
TI  - [Subependymal pseudocysts in the fetal brain revealing Zellweger syndrome].
AB  - Prognosis of subependymal pseudocyst is poor when associated with other
      anomalies. They can be caused by infectious, vascular, chromosomal or metabolic
      disorders but are rarely described in the antenatal period. We report the
      prenatal diagnosis of subependymal pseudocyst by MRI after prenatal detection of
      isolated ventriculomegaly at 23 weeks gestation. The karyotype was normal. The
      diagnostic of Zellweger syndrome was suspected and was confirmed after birth by
      metabolic studies. Metabolic studies with culture of chorionic villus cell is
      indicated for subsequent pregnancies.

PMID- 15170430
TI  - [Repeated thromboembolism during pregnancy with constitutional antithrombin
      deficiency].
AB  - We report the case of a twenty-three-year old woman with constitutional
      antithrombin deficiency, who had oral anticoagulation since she was four years
      old. During her first pregnancy, after the introduction of unfractionated heparin
      prophylactic therapy, she presented a first venous thromboembolism at nine weeks,
      and a second one with low-molecular-weight heparin therapy at nineteen weeks.
      Because of a severe antithombin deficiency, regular infusions of antithrombin
      concentrates were necessary until delivery to ensure effective anticoagulation by
      heparin. Patients with antithrombin deficiency have a very high risk of venous
      thromboses during the pregnancy and post-partum. We discuss the significant
      points of management for this period.

PMID- 15170432
TI  - [Labor pain and obstetric analgesia].
AB  - GOAL AND METHODS: Labor pain is of major concern since most parturients
      experience significant pain of extremely severe intensity for many. The purpose
      of this review was to provide an overview of the mechanisms and pathways of labor
      pain (including new insights on integration of the nociceptive signal) and to
      emphasize the need of effective labor pain relief. RESULTS: Labor pain can have
      deleterious effects on the mother, on the fetus and on labor outcome itself.
      Among the current methods of obstetric analgesia, regional analgesia (the most
      widespread technique being epidural analgesia) offers the best
      effectiveness/safety ratio thanks to pharmacological innovations. Systemic
      analgesia (parenteral opioids, nonopioid painkillers and inhaled anesthetic
      agents) provides an alternative to regional analgesia but remains less effective
      and more hazardous. Non-drug approaches (namely psychoprophylaxis and physical
      methods) may be effective when used with epidural analgesia but are often not
      potent enough when used alone. CONCLUSION: Despite its complex pathophysiology,
      labor pain can be efficiently managed. Thanks to multidisciplinary care,
      obstetric analgesia (mainly epidural analgesia) prevents deleterious effects of
      labor pain on the mother and fetus.

PMID- 15170433
TI  - [Kartagener's syndrome and infertility: observation, diagnosis and treatment].
AB  - Primary ciliary dyskinesia is a rare etiology of sterility in man (prevalence
      between 1/6000 and 1/40000). Kartagener's syndrome is an autosomal recessive
      disorder, characterized by total or partial dysfunction of the ciliary or
      flagellated cells. This syndrome associates situs inversus, sinusitis,
      bronchiectasis and occasionally sterility in males. We report a case of immotile
      cilia syndrome with male infertility and compare the data with four other couples
      reported in the literature (two couples in Germany, two in the United States).
      The difficulty is to select an alive sperm cell for ICSI.

PMID- 15170434
TI  - [Alternatives to hormone replacement therapy for menopause: an epidemiological
      evaluation].
AB  - OBJECTIVE: Recent results put into question the risks/benefits ratio of hormone
      replacement therapy and emphasize the importance of precise knowledge of the
      effects of other treatments that exist for postmenopausal symptoms or diseases.
      Our aim is to analyze their effect. METHODS: A review of randomized trials or
      epidemiological studies was undertaken. RESULTS: Bisphophonates, calcitonin,
      parathormone, strontium ranelate, calcium and vitamin D have specific effects on
      bone. The efficacy of bisphophonates for prevention and treatment of osteoporosis
      has been proven and parathormone and strontium ranelate seem promising. These
      treatments are useful for women at high risk of osteoporosis who do not suffer
      from menopausal symptoms. Tibolone, SERMs and phytoestrogens exert effects on
      various tissues. SERMs are very promising, but they do not improve climacteric
      symptoms and their long term effects are still unknown. Tibolone has beneficial
      effects on climacteric symptoms and on bone loss, but recent results concerning
      its effects on the risk of breast cancer call into question its interest. The
      beneficial effects of phytoestrogens on bone and on vasomotor symptoms need to be
      confirmed. CONCLUSION: At this time, none of the existing treatments for
      postmenopausal symptoms or diseases is ideal. The existence of several options
      for treatments of symptoms or diseases of the postmenopause is helpful as it
      affords several choices for physicians and for women who sometimes need to be
      treated for many years. However several questions remain unanswered concerning
      the long term effects of these treatments.

PMID- 15170435
TI  - [Does tension-free vaginal tape (TVT) have a place in the treatment of sphincter
      incompetence?].
AB  - OBJECTIVE: The objective of this article is to estimate results and place of TVT
      in female stress urinary incontinence with intrinsic sphincter incompetence.
      MATERIAL AND METHOD: This was a retrospective study over a period of 57 months in
      a population of 38 patients treated by TVT for sphincter incompetence with or
      without inefficient pressure transmission. Mean patient age was 52 years.
      Fourteen patients (37%) had a history of incontinence surgery. The physical
      examination demonstrated urethral mobility in 22 patients (58%) and positive
      Bonney or Jacquetin tests in 15 patients (39%). Mean maximum urethral closure
      pressure was 40 cm H2O, with 12 patients (32%) 30 cm. Six patients (16%) had
      detrusor instability. Seven patients (18%) had pure sphincter incompetence.
      RESULTS: Median follow-up was eight months (two months to 32 months). Twenty five
      patients (66%) were cured, nine (24%) improved and treatment failed in four
      (10%). Results are less satisfactory for patients with preliminary failure of
      incontinence surgery, fixed urethra, pure sphincter incompetence or with detrusor
      instability without inefficient pressure transmission. The only major
      complication was an expulsion of the prosthesis. CONCLUSION: Results of TVT in
      sphincter incompetence are slightly less satisfactory than in pure urinary stress
      incontinence. In a short follow-up, they are comparable in sphincter incompetence
      to those of sling procedures which are the current gold standard. Risk of urinary
      retention is lesser. The minimally invasive nature of TVT suggests that it will
      replace sling procedures in the future for this particular indication. Longer
      follow-up will be necessary for confirmation.

PMID- 15170436
TI  - [A new hysteroscopic method for sterilization: 45 patients].
AB  - OBJECTIVES: French study of the feasibility and safety of a new hysteroscopic
      method for sterilization under local anesthesia. MATERIALS AND METHODS: After
      information, all candidates for sterilization were invited to choose between the
      laparoscopic or hysteroscopic methods. Essure performed under local analgesia was
      used for hysteroscopic sterilization. Operative time, intensity of pain using a
      visual analog scale and secondary discomfort were recorded. RESULTS: A cohort of
      57 women were enrolled in this study and 45 chose hysteroscopy. Two were excluded
      after discovery of an intrauterine pathology during the hysteroscopic procedure.
      Placement of a bilateral device was successful in 41 patients (90.3%); under
      local analgesia only in 29 patients (68.3%). Mean time needed for device
      placement was 25.6 9 min and hospital stay was 9.8 hours. Pain was scored 56/100
      on the visual analog scale. CONCLUSION: Laparoscopy remains the mainstay method
      used for sterilization but does involve risks. Hysteroscopic device placement
      seems to be safe, rapid and an effective procedure.

PMID- 15170437
TI  - [Usefulness of a collecting bag for the diagnosis of post-partum hemorrhage].
AB  - OBJECTIVE: Depending on the country and the publications, post-partum hemorrhage
      (PPH) is either the first or second cause of maternal death in the world,
      including in developed countries. It remains a significant source of morbidity,
      severe anemia, blood transfusion, transfusion complications, acquired coagulation
      disorders and hemostasis hysterectomy. Visual assessment underestimates the
      amount of blood loss in around 45% of cases. Emergency treatment is therefore
      sometimes undertaken with some delay, giving time for Disseminated Intravascular
      Coagulation (DIC) to occur, which worsens the prognosis. A collecting plastic bag
      put under the pelvis of the mother just after delivery is a quantitative and
      objective method of measuring blood loss. The objective was to assess
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), studying correlation between bag's volume and hemoglobin and
      hematocrit variation. MATERIALS AND METHODS: Included outpatients were women with
      unique pregnancy at term. Breech presentations were excluded. We measured serum
      hemoglobin and hematocrit just after admission for labor. A collecting bag,
      placed under the pelvis of each woman just after birth, was weighted after
      delivery. Serum hemoglobin and hematocrit were again assessed at three days. Post
      partum hemorrhage was defined by a fall of hematocrit more than 10 points (delta
      Ht), or by a fall of hemoglobin more than 3g/dL (delta Hb). RESULTS: From January
      2003 to May 2003, 272 patients were included. 8.9% of the results were unuseful
      (n=24). The mean volume of blood loss was 190 ml (5th p=29 ml, 10th p=48 ml, 90th
      p=610 ml, 95th p=824 ml). The mean delta Ht was 2.7 +/- 4 pts (16.5 / -4.8). The
      mean delta Hb was 1.2 +/- 1.4 g/dL (5.9 / -1.5). For a delta Ht=10 the calculated
      bag volume was 564 ml. With this cut off we noted 5.5% PPH (n=15)
      prevalence=0.06. Sensitivity=34.21%. Specificity=99%. PPV=86%. NPV=90.38%. For a
      delta Hb=3 the calculated bag volume was 486 ml. With this cut off we noted 10.7%
      PPH (n=24) prevalence of PPH=0.1. Sensitivity=38.77%. Specificity=95.96%, PPV=67.
      85%. NPV=87.7%. CONCLUSION: The collecting pelvis bag is a rapid and precise
      procedure to diagnose PPH in the delivery room. It also enables a visual and
      quantitative non-subjective estimation of blood loss. Because of its simplicity
      and very low cost, the collecting pelvis bag should be used widely as a routine
      preventive measure.

PMID- 15170439
TI  - [Massive fetomaternal hemorrhage revealed by decreased perception of active fetal
      movements].
AB  - Massive fetomaternal hemorrhage is rare. Without risk factors, early diagnosis is
      difficult to establish. The clinical and paraclinical manifestations are not
      specific and depend on fetal compensatory reactions; the Kleihauer test will
      confirm the diagnosis. Two cases of massive fetomaternal hemorrhage preceded by
      decreased fetal movements are presented here. An emergency delivery by cesarean
      section saved one child. Despite a favorable clinical and laboratory evaluation,
      one fetal death could not be avoided. Early diagnosis and specialised management
      are essential to improve prognosis. These observations indicate that it is
      mandatory to carry out a Kleihauer test whenever a decrease of fetal movements is
      observed.

PMID- 15170438
TI  - [Pregnancy after adjustable gastric band for morbid obesity: specific features of
      follow-up].
AB  - OBJECTIVE: To give pregnant women treated with an adjustable gastric band
      specific information on pregnancy and fetal outcome. MATERIAL AND METHOD: Case
      report and discussion of the main complications and specific features follow-up
      during pregnancy. RESULTS: In our patient the gastric band was adjusted to
      prevent first trimester vomiting. Diet was not modified. Weight gain during
      pregnancy was limited to four kilograms (kg). A hypotrophic girl was delivered by
      cesarean section. CONCLUSION: The main difficulties concern first trimester
      vomiting and dietary advice. Information regarding the effects of gastric band on
      pregnancies is limited and requires further investigations. A national file on
      outcome of pregnancy in women with gastric bands would be useful to establish
      appropriate recommendations.

PMID- 15170441
TI  - [Maternal toxoplasmosis before conception and chorioretinitis in twin sisters].
AB  - A maternal toxoplasmosis before conception is exceptionally transmitted to the
      fetus. We report an observation of twin sisters who presented congenital
      toxoplasmosis with chorioretinitis detected at nine months of age. The anamnesis
      revealed that the mother had had toxoplasmosis one month before conception. In
      the event of preconceptual infections, we propose fetal ultrasonography,
      histological examination of the placenta at delivery, as well as a pediatric
      follow-up of the infants (serological samples every month, cranial
      ultrasonography, fundus oculi).

PMID- 15170440
TI  - [Post mortem brain MRI: an alternative for pathology examination in Bourneville
      tuberous sclerosis of the fetus?].
AB  - Antenatal discovery of cardiac rhabdomyomes evokes the diagnosis of Bourneville's
      disease. Antenatal brain exploration with ultrasonography and magnetic resonance
      imaging (MRI) can highlight cerebral localizations. In the event of termination
      of pregnancy, confirmation of the cerebral lesions can be achieved with post
      mortem MRI as well as pathology examination. MRI can be usefully employed in the
      event pathology examination is not feasible.

PMID- 15170442
TI  - [Ovarian fibroma associated with Demons-Meigs syndrome and elevated CA 125].
AB  - We report a rare case of ovarian fibroma in a young woman. When ovarian masse is
      associated with Meigs' syndrome and elevated CA 125 serum level a malignant
      process may be suspected. But a negative cytological examination of ascitic
      effusion and absence of peritoneal implant recommend performing limited surgical
      procedures.

PMID- 15170443
TI  - Smoking in pregnancy: a need for improving information available to pregnant
      women on deleterious effects of smoking on pregnancy outcome.

PMID- 15170444
TI  - Linkage analysis of smoking initiation and quantity in Dutch sibling pairs.
AB  - The heritability of smoking initiation (SI) and number of cigarettes smoked (NC)
      was determined in 3657 Dutch twin pairs. For SI a heritability of 36% was found
      and for NC of 51%. Both SI and NC were also significantly influenced by
      environmental factors shared by family members. The etiological factors that
      influence these traits partly overlap. Linkage analyses were performed on data of
      536 DZ twins and siblings from 192 families, forming 592 sibling pairs. Results
      suggested QTLs on chromosome 6 (LOD=3.05) and chromosome 14 (LOD=1.66) for SI and
      on chromosome 3 (LOD=1.98) for NC. Strikingly, on chromosome 10 a peak was found
      in the same region for both SI (LOD=1.92) and for NC (LOD=2.29) which may partly
      explain the overlapping etiological factors for SI and NC.

PMID- 15170445
TI  - The anti-angiogenic basis of metronomic chemotherapy.

PMID- 15170446
TI  - Exploiting tumour hypoxia in cancer treatment.

PMID- 15170447
TI  - Dissecting the metastatic cascade.

PMID- 15170448
TI  - The potential of positron-emission tomography to study anticancer-drug
      resistance.

PMID- 15170449
TI  - A renaissance for SRC.

PMID- 15170450
TI  - Yeast as a model system for anticancer drug discovery.

PMID- 15170451
TI  - The Icelandic Cancer Project--a population-wide approach to studying cancer.

PMID- 15170452
TI  - Spotlight on membrane traffic. Nothing to declare?

PMID- 15170453
TI  - Organelle identity and the organization of membrane traffic.
AB  - Generating and maintaining features that distinguish one organelle from another
      is essential for accurate membrane traffic. Recent work has revealed that
      organelles express 'identity' by the local generation of activated GTP-binding
      proteins and lipid species. These recruiting determinants are then recognized by
      cytosolic proteins that facilitate the formation and delivery of vesicles at the
      correct compartment.

PMID- 15170454
TI  - Cdc14 phosphatase resolves the rDNA segregation delay.
AB  - Sister chromatid segregation in anaphase of mitosis is initiated through cleavage
      of cohesin by the protease separase. Two studies now show that this view is valid
      for most chromosomal DNA, but not for the highly repetitive ribosomal DNA (rDNA)
      and telomeres. The disjunction of these regions of the chromosome occurs in mid
      anaphase, long after cohesin cleavage, and is regulated by the conserved
      phosphatase Cdc14.

PMID- 15170455
TI  - Fusion has found its calcium sensor.
AB  - Synaptic vesicle exocytosis, a finely tuned process that results in rapid
      neurotransmitter release, is still not fully understood. Studies in a simple
      reconstituted lipid bilayer system have now definitively demonstrated that
      synaptotagmin has a key role in calcium-mediated exocytosis and have also
      revealed additional aspects of exocytic fusion.

PMID- 15170456
TI  - Tip-ping off the COPs.

PMID- 15170457
TI  - Hsp90 invades the outside.
AB  - Metalloproteases are required for the invasive nature of cancer cells.
      Surprisingly, the cytosolic molecular chaperone Hsp90 is now shown to promote
      maturation of the extracellular metalloprotease MMP2. This finding extends the
      multiplicity of roles assigned to the Hsp90 family to a new function outside the
      cell.

PMID- 15170459
TI  - Merging cultures in the study of membrane traffic.
AB  - Membrane and organelle assembly has emerged as a dominant theme in cell biology
      of the twenty-first century. Current approaches and questions have been
      formulated as a result of numerous historical threads that together weave a
      complex picture of cellular compartments. The confluence of morphologic, genetic
      and biochemical approaches laid the foundations for study in this area, and they
      continue to strengthen our understanding of this essential aspect of cell
      structure and function.

PMID- 15170460
TI  - PI-loting membrane traffic.
AB  - Phosphoinositides (PIs) undergo phosphorylation/dephosphorylation cycles through
      organelle-specific PI kinases and PI phosphatases that lead to distinct
      subcellular distributions of the individual PI species. Specific PIs control the
      correct timing and location of many trafficking events. Their ultimate mode of
      action is not always well defined, but it includes localized recruitment of
      transport machinery, allosteric regulation of PI-binding proteins and changes in
      the physical properties of the membrane.

PMID- 15170461
TI  - Mediterranean views on epithelial polarity.
AB  - Developmental and cell biologists viewed polarity through each other's eyes at
      the EMBO workshop on Epithelial Polarity in Development and Disease, March 27-31
      2004, in Carry-le-Rouet, France, a small village west of Marseille on the rocky
      Mediterranean coast. The presentations highlighted our growing understanding, not
      only of the molecular mechanisms underlying polarity and the conservation of
      polarity complexes from worms to mammals, but also the diverse roles that
      epithelial polarity has during development.

PMID- 15170462
TI  - Acute amygdalar activation induces an upregulation of multiple monoamine G
      protein coupled pathways in rat hippocampus.
AB  - A "partial" rodent model for schizophrenia has been used to characterize the
      regulation of hippocampal genes in response to amygdalar activation. At 96 h
      after the administration of picrotoxin into the basolateral nucleus, we have
      observed an increase in the expression of genes associated with 18 different
      monoamine (ie adrenergic alpha 1, alpha 2 and beta 2, serotonergic 5HT5b and
      5HT6, dopamine D4 and muscarinic m1, m2 and m3) and peptide (CCK A and B,
      angiotensin 1A, mu and kappa opiate, FSH, TSH, LH, GNRH, and neuropeptide Y) G
      protein coupled receptors (GPCRs). These latter receptors are associated with
      three different G protein signaling pathways (Gq, Gs, and Gi) in which
      significant changes in gene expression were also noted for adenylate cyclase
      (AC4), phosphodiesterase (PDE4D), protein kinase A (PKA), and protein kinase C
      (PKC). Quantitative RT-PCR was used to validate the results and demonstrated that
      there were predictable increases of three GPCRs selected for this analysis,
      including the dopamine D4, alpha 1b, and CCK-B receptors. Eight out of the nine
      monoamine receptors showing these changes have moderate to high affinity for the
      atypical antipsychotic, clozapine. Taken together, these results suggest that
      amygdalar activation may play a role in the pathophysiology and treatment of
      psychosis by regulating the activity of multiple GPCR and metabolic pathways in
      hippocampal cells.

PMID- 15170463
TI  - Role of parents in the determination of the food preferences of children and the
      development of obesity.
AB  - The role of parental behaviour in the development of food preferences is
      considered. Food preferences develop from genetically determined predispositions
      to like sweet and salty flavours and to dislike bitter and sour tastes.
      Particularly towards the second year of life, there is a tendency to avoid novel
      foods (neophobia). Food aversions can be learnt in one trial if consumption is
      followed by discomfort. There is a predisposition to learn to like foods with
      high-energy density. However, from birth genetic predispositions are modified by
      experience and in this context during the early years parents play a particularly
      important role. Parental style is a critical factor in the development of food
      preferences. Children are more likely to eat in emotionally positive atmospheres.
      Siblings, peers and parents can act as role models to encourage the tasting of
      novel foods. Repeated exposure to initially disliked foods can breakdown
      resistance. The offering of low-energy-dense foods allows the child to balance
      energy intake. Restricting access to particular foods increases rather than
      decreases preference. Forcing a child to eat a food will decrease the liking for
      that food. Traditionally, educational strategies have typically involved attempts
      to impart basic nutritional information. Given the limited ability of information
      to induce changes in behaviour, an alternative strategy would be to teach parents
      about child development in the hope that an understanding of the characteristic
      innate tendencies and developmental stages can be used to teach healthy food
      preferences.

PMID- 15170464
TI  - Effects of a multidisciplinary weight loss intervention on anaerobic and aerobic
      aptitudes in severely obese adolescents.
AB  - OBJECTIVE: To investigate if a multidisciplinary weight loss programme in
      adolescents suffering severe obesity allows an improvement of anaerobic and
      aerobic aptitudes. DESIGN: In all, 55 adolescents (33 girls and 22 boys)
      suffering from severe obesity were enrolled in an interdisciplinary weight
      reduction programme lasting 6-12 months. Progressive submaximal physical activity
      was performed and national dietary allowances for adolescents with low levels of
      physical activity were provided. MEASUREMENTS: Total and regional body
      composition and anaerobic aptitudes (handgrip strength (HGS), vertical jump
      height (VJH)) and aerobic aptitudes (maximal aerobic power (MAP), maximal oxygen
      uptake (VO(2max))) were measured before and after weight loss. RESULTS: The mean
      reduction of body mass index (BMI) was similar in girls (21.4+/-5.9%) and boys
      (23.7+/-6.4%). Fat mass (FM) steepest drop was observed in the trunk (-63.2+/
      10.1% in boys and -51.5+/-11.4% in girls). The total lean mass (LM) did not vary
      in both sexes. Right HGS and VJH increased in both sexes (P<0.05), whereas left
      HGS increased only in boys. MAP and VO(2max) per kg BW increased (P< 0.0001) in
      both sexes (2.3+/-0.3 vs 1.7+/-0.3 W/kg and 32.8+/-4.5 vs 26.7+/-4.1 ml/min/kg in
      girls and 2.8+/-1.9 vs 1.9+/-0.4 W/kg and 39.1+/-6.3 vs 27.9+/-5.1 ml/min/kg in
      boys, respectively), whereas MAP and VO(2max) in absolute value and per kg LM
      increased only in boys (P=0.04). Total LM was the strongest determinant of HGS,
      VJH, MAP and VO(2max) in both sexes (P<0.005). CONCLUSIONS: Multidisciplinary
      weight reduction programme including moderate dietary restriction in combination
      with regular physical training induced an improvement of anaerobic and aerobic
      aptitudes, a marked reduction of obesity and a preservation of LM in severely
      obese adolescents.

PMID- 15170465
TI  - Overweight in children is associated with arterial endothelial dysfunction and
      intima-media thickening.
AB  - OBJECTIVE: We sought to study arterial endothelial function and carotid intima
      media thickness (IMT), both early markers of atherosclerosis, in overweight
      compared to normal children. DESIGN: Case-control comparison. SUBJECTS: A total
      of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25+/-3)
      aged 9-12 y and 36 age- and gender-matched nonobese healthy children (BMI<21)
      from a school community. MEASUREMENTS: The key parameters were: BMI, arterial
      endothelial function (ultrasound-derived endothelium-dependent dilation) and
      carotid artery IMT. The secondary parameters measured included body fat content,
      waist-hip ratio (WHR), blood pressures, blood lipids, insulin and glucose.
      RESULTS: The two groups were well matched for blood pressures, cholesterol and
      glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting
      blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese
      children. Overweight was associated with impaired arterial endothelial function
      (6.6+/-2.3 vs 9.7+/-3.0%, P<0.0001) and increased carotid IMT (0.49+/-0.04 mm vs
      0.45+/-0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with
      BMI (P<0.003) on multivariate analysis. CONCLUSION: Obesity, even of mild-to
      moderate degree, is independently associated with abnormal arterial function and
      structure in otherwise healthy young children.

PMID- 15170467
TI  - Thoughts for the new Europe.

PMID- 15170466
TI  - Insulin resistance syndrome in a representative sample of children and
      adolescents from Quebec, Canada.
AB  - OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a
      representative sample of youth. To test for the independent contribution of
      insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To
      identify the underlying components of IRS. To examine the relationship between
      adiposity and fasting plasma levels of free fatty acids (FFA). METHODS: In 1999,
      we conducted a school-based survey of a representative sample of youth aged 9, 13
      and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized
      clinical measurements and a fasting blood sample were available for 2244
      subjects. Fasting insulin and HOMA were used as surrogate measures of IR.
      RESULTS: In all age-sex groups, adiposity indices, blood pressure (BP), plasma
      glucose and triglycerides (TG) increased significantly with increasing insulin
      quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS
      defined as hyperinsulinaemia combined with two or more risk factors including
      overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C,
      was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the
      prevalence of IRS across ages or between sexes. The independent contribution of
      adiposity to clustering of risk factors was stronger than that of fasting insulin
      (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids,
      BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting
      that more than one pathophysiologic process underlies IRS. Although elevation of
      FFA might be in the causal pathway linking obesity to IR, we did not detect any
      consistent association between measures of fatness and fasting plasma FFA.
      CONCLUSION: IRS is highly prevalent in youth, even among children as young as age
      9 y. Factor analysis identifies three physiologic domains within IRS with a
      unifying role for markers of IR and adiposity.

PMID- 15170468
TI  - The evolution of molecular biology.

PMID- 15170469
TI  - Overcoming resistance.

PMID- 15170470
TI  - Embryos, cells and God.

PMID- 15170471
TI  - Like a snake in the grass.

PMID- 15170474
TI  - CLC-K channels: if the drug fits, use it.

PMID- 15170475
TI  - The J-protein family: modulating protein assembly, disassembly and translocation.
AB  - DnaJ is a molecular chaperone and the prototypical member of the J-protein
      family. J proteins are defined by the presence of a J domain that can regulate
      the activity of 70-kDa heat-shock proteins. Sequence analysis on the genome of
      Saccharomyces cerevisiae has revealed 22 proteins that establish four
      distinguishing structural features of the J domain: predicted helicity in
      segments I-IV, precisely placed interhelical contact residues, a lysine-rich
      surface on helix II and placement of the diagnostic sequence HPD between the
      predicted helices II and III. We suggest that this definition of the J-protein
      family could be used for other genome-wide studies. In addition, three J-like
      proteins were identified in yeast that contain regions closely resembling a J
      domain, but in which the HPD motif is non-conservatively replaced. We suggest
      that J-like proteins might function to regulate the activity of bona fide J
      proteins during protein translocation, assembly and disassembly.

PMID- 15170477
TI  - Signal transduction during light-quality acclimation in cyanobacteria: a model
      system for understanding phytochrome-response pathways in prokaryotes.
AB  - The colorful process of complementary chromatic adaptation (CCA), in which
      cyanobacteria dramatically alter their pigmentation in response to ambient light
      color changes, has intrigued scientists for more than a century. Over the past
      four decades, intensive research on the model organism Fremyella diplosiphon has
      revealed many details of the photobiology and molecular biology of this process,
      which includes restructuring of these organism's photosynthetic light-harvesting
      antennae, called phycobilisomes. This restructuring involves changes in
      transcription of genes encoding phycobilisome components. These genes have been
      cloned and their patterns of light-responsive expression characterized. In the
      past ten years, attention has focused on the signal transduction mechanism(s)
      through which cyanobacteria sense and respond to changes in ambient light color.
      Genetic approaches led to the isolation of signal transduction components that
      control light-color responses in F. diplosiphon. Several of these appear to be
      within a complex phosphorelay that is in part controlled by a photoreceptor
      called RcaE, the founding member of a large, novel class of prokaryotic
      photoreceptors with similarity to both plant phytochrome photoreceptors and
      sensor histidine kinases. The strong foundation of knowledge provided by years of
      research on CCA makes this a powerful model system for studying signal
      transduction systems controlled by prokaryotic phytochromes. In this regard,
      recent results demonstrate that multiple light sensing systems control this
      organism's responses to changes in light quality and that large numbers of genes
      are differentially regulated during this process.

PMID- 15170478
TI  - Photoresponsive cAMP signal transduction in cyanobacteria.
AB  - The molecular mechanism of cAMP-mediated signal transduction from light reception
      to the physiological response via regulation of gene expression in cyanobacteria
      is described based on our recent works. Cyanobacteria are known as the organisms
      that acquired oxygen-evolving, higher plant type photosynthesis. We have found
      that the cellular cAMP level in the filamentous cyanobacteria Anabaena was
      oppositely regulated by red and far-red light, i.e., decreasing and increasing,
      respectively, suggesting that a phytochrome-like red/far-red photoreversible
      pigment regulates the activity of a certain adenylate cyclase. On the other hand,
      in the unicellular cyanobacterium Synechocystis cellular cAMP content was
      increased by blue light irradiation, which led to stimulation of cell motility.
      The cAMP signaling pathway is known to play an important role in the regulation
      of various biological activities by altering enzyme activities or controlling
      gene expression levels in both prokaryotes and eukaryotes. We have isolated genes
      for adenylate cyclases and cAMP receptor proteins and characterized their
      molecular properties. Disruption of these genes resulted in the loss of cell
      motility. It is concluded that the light signal was transmitted by cAMP signal
      cascade in cyanobacteria.

PMID- 15170476
TI  - Plants: the latest model system for G-protein research.
AB  - In humans, heterotrimeric G proteins couple stimulus perception by G-protein
      coupled receptors (GPCRs) with numerous downstream effectors. By contrast,
      despite great complexity in their signal-transduction attributes, plants have a
      simpler repertoire of G-signalling components. Nonetheless, recent studies on
      Arabidopsis thaliana have shown the importance of plant G-protein signalling in
      such fundamental processes as cell proliferation, hormone perception and ion
      channel regulation.

PMID- 15170479
TI  - Phototactic motility in the unicellular cyanobacterium Synechocystis sp. PCC
      6803.
AB  - Synechocystis sp. PCC 6803 is a unicellular motile cyanobacterium that shows
      positive and negative phototaxis on agar plates under lateral illumination.
      Recent studies on the molecular mechanisms of the phototactic motility of
      Synechocystis have revealed that a number of genes are responsible for its pilus
      dependent motility and phototaxis. Here we describe what is known about these
      genes. We also discuss the novel spectral properties of the phytochrome-like
      photoreceptor PixJ1 in Synechocystis, that is essential for positive phototaxis
      and which has revealed the existence of a new group of chromophore-binding
      proteins in cyanobacteria.

PMID- 15170480
TI  - Photoactive yellow protein, bacteriophytochrome, and sensory rhodopsin in purple
      phototrophic bacteria.
AB  - The purple photosynthetic bacteria contain a large variety of sensory and
      regulatory proteins, and those responding to light are among the most
      interesting. These currently include bacteriophytochrome (Bph), sensory rhodopsin
      (SR), and photoactive yellow protein (PYP), which all appear to function as light
      sensors. We herein interpret new findings within the context of current
      knowledge. For greater detail, the reader is referred to comprehensive reviews on
      these topics. Of the three proteins, only PYP has been well-characterized in
      terms of structure and physical-chemical properties in the purple bacteria,
      although none have well-defined functions. New findings include a cluster of six
      genes in the Thermochromatium tepidum genome that encodes presumed sensory
      rhodopsin and phototaxis proteins. T. tepidum also has a gene for PYP fused to
      bacteriophytochrome and diguanylate cyclase domains. The genes for PYP and its
      biosynthetic enzymes are associated with those for gas vesicle formation in
      Rhodobacter species, suggesting that one function of PYP is to regulate cell
      buoyancy. The association of bacteriophytochrome genes with those for reaction
      centers and light-harvesting proteins in Rhodopseudomonas palustris suggests that
      the photosynthetic antenna as well as the reaction center are regulated by Bphs.
      Furthermore, Rc. centenum PPR is reversibly photobleached at 702 nm rather than
      red-shifted as in other phytochromes, suggesting that PPR senses the intensity of
      white light rather than light quality. PYP from Halorhodospira(aka
      Ectothiorhodospira)halophila is of special interest because it has become the
      structural prototype for the PAS domain, a motif that is found throughout the
      phylogenetic tree and which plays important roles in many signaling pathways.
      Thus, the structural and photochemical characterization of PYP, utilizing site
      directed mutagenesis, provides insights into the mechanism of signal
      transduction.

PMID- 15170482
TI  - Transient movement of helix F revealed by photo-induced inactivation by reaction
      of a bulky SH-reagent to cysteine-introduced pharaonis phoborhodopsin (sensory
      rhodopsin II).
AB  - Pharaonis phoborhodopsin (ppR) is a photosensor of negative phototaxis in
      Natronomonas (Natronobacterium) pharaonis, an alkalophilic halophile. This
      protein has seven transmembrane helices into which a chromophore, all-trans
      retinal, binds to a specific lysine residue (located in helix G)via a protonated
      Schiff base. Various mutants were engineered to have a single cysteine in the F
      helix. In the presence of a bulky fluorescent SH-reagent, MIANS, (2-(4'
      maleimidylanilino)naphthalene-6-sulfonic acid, illumination decreased the
      photoreactivity or flash-yield (absorbance deflection immediately after the
      flash) of the L163C ppR mutant (in which Leu-163 was replaced with Cys) without
      changing the photocycling rate. The fluorescence of the isolated protein
      increased with increasing illumination. These observations suggest that during
      photocycling, the space around Cys-163 in the F-helix might open, permitting
      reaction with the relatively large molecule. This reaction occurred only at the M
      state and not at the O-state. The implications are discussed.

PMID- 15170481
TI  - Tryptophan fluorescence monitors structural changes accompanying signalling state
      formation in the photocycle of photoactive yellow protein.
AB  - Photoactive yellow protein, a small, water-soluble blue-light absorbing
      photoreceptor protein from Ectothiorhodospira(Halorhodospira)[space]halophila has
      a structure with two hydrophobic cores, of which the main one houses its light
      sensitive chromophore (p-coumaric acid), separated by a central [small beta]
      sheet. This photoreceptor protein contains a single tryptophan residue (W119)
      that is situated at the interface between the central beta-sheet and its N
      terminal cap. The fluorescence properties of W119 in the dark state pG
      (lambda(max)= 328 nm; Phi(fl)= 0.01; nearly pH-independent) are typical for a
      buried tryptophan in a hydrophobic environment with significant quenching by
      nearby amino acid residues. Signalling state formation leads to pH-dependent
      fluorescence changes: At pH values <6.5 the fluorescence emission increases, with
      a minor blue shift of the emission maximum. Above this pH, the emission maximum
      of the tryptophan shifts considerably to the red, whereas its total intensity
      decreases. These results further support the contention that signalling state
      formation in PYP leads to significant changes in the structure of this protein,
      even at sites that are at a considerable distance from the chromophore. The
      nature of these changes in pB, however, depend upon the pH imposed upon the
      protein: At slightly alkaline pH, which presumably is closest to the pH to which
      this protein is exposed in vivo, these changes lead to an exposure of the part of
      the central beta-sheet harbouring W119. At slightly acidic pH the polarity of the
      environment of W119 is hardly affected by the formation of the signalling state
      but the quenching of its fluorescence emission, possibly by nearby amino acids,
      is reduced. On the other hand, its accessibility for quenching by small molecules
      in the solution is enhanced at acidic and alkaline pH in the signalling state
      (pB) compared to the dark state (pG). This latter observation points towards a
      more flexible structure of the N-terminal cap, having a looser interaction with
      the central beta-sheet in pB.

PMID- 15170483
TI  - Sensory rhodopsin II and bacteriorhodopsin: light activated helix F movement.
AB  - EPR spectroscopy in combination with site directed spin labeling (SDSL) has
      become a valuable tool for structural investigations as well as for kinetic
      studies on proteins. This method has been especially useful for membrane proteins
      in yielding structural and functional data. This information is not easily
      available from other techniques, like, e.g., X-ray crystallography or electron
      microscopy. In the first part of this two part review, the topology of the
      sensory rhodopsin II/transducer complex (NpSRII/NpHtrII) derived from EPR
      constraints is compared to that obtained from X-ray crystallography. In the
      second part, the helix F movement observed for both sensory rhodopsin and
      bacteriorhodopsin is evaluated and discussed in order to establish a common
      mechanism after photoreceptor activation.

PMID- 15170484
TI  - Light-induced intramolecular charge movements in microbial rhodopsins in intact
      E. coli cells.
AB  - Microbial rhodopsins undergo cyclic photochemical reactions (photocycles) in
      which proton transfers and conformational changes result in charge displacements
      during transitions between photocycle intermediates. We report a new
      photoelectric method to monitor charge movements during rhodopsin photocycling
      with fast kinetic resolution in suspensions of intact E. coli cells. The method
      monitors electrical currents resulting from asymmetric photoexcitation of
      microbial rhodopsins by a unilateral laser flash, and kinetically resolves
      intramolecular charge movements. We investigated E. coli-expressed proton
      transporting rhodopsins, specifically green- and blue-absorbing proteorhodopsins
      (GPR and BPR, respectively) from uncultivated marine plankton, and sensory
      rhodopsins, namely receptors from Natronomonas pharaonis and Anabaena (Nostoc)
      sp. PCC7120. Kinetic components of the currents correlate with photochemical
      transformations of the pigments, and the integrated current measures net
      transport by the proton-pumping rhodopsins. The photoelectric measurements
      distinguish between known light-driven transporters and photosensors, and reveal
      differences in proton transfer reactions in the two tested proton pumps.
      Screening of nine newly identified proteorhodopsins reveals two with GPR-type
      charge movements, five with BPR-type, and two with the characteristics of the
      sensory rhodopsins. The approach developed in the present work provides a direct,
      rapid and informative method for studying electrogenic events in rhodopsin
      photocycles and also gives a clue to functions of newly found microbial
      rhodopsins in nature.

PMID- 15170485
TI  - Fungal rhodopsins and opsin-related proteins: eukaryotic homologues of
      bacteriorhodopsin with unknown functions.
AB  - In the last decade, several genome sequencing projects revealed the existence of
      previously unknown photoreceptors. Among those are eukaryotic rhodopsins of
      haloarchaeal type, mostly represented by fungal sequences. We have classified and
      analyzed seventy-seven of these fungal proteins, which show a high similarity of
      their putative transmembrane regions to those of bacteriorhodopsin. Those
      sequences can be divided into the two subgroups, fungal rhodopsins (RDs) and
      opsin-related proteins (ORPs), the latter lacking the lysine residue necessary
      for retinal binding. We have analyzed the conservation pattern of the residues
      known to have functional or structural importance in bacteriorhodopsin and
      discussed dramatic differences in the conservation between RDs and ORPs. We found
      many cases of multiple forms of RDs and/or ORPs and examined possible reasons for
      such multiplicity. For some species the reason may lie in functional
      photobiological diversification, while for the others it follows the pattern of
      evolutionary recent genome duplication and possible functional redundancy.

PMID- 15170486
TI  - The bacterial counterparts of plant phototropins.
AB  - We review and analyze the growing family of bacterial proteins carrying the LOV
      (light oxygen voltage) motif, a flavin-binding photoactive domain first
      characterized in plant blue-light receptors, the phototropins. A total of 29
      sequences encoding LOV-proteins can be detected in the genomes of 24 bacterial
      species. In the bacterial LOV domains, the majority of the amino acids known to
      interact with the flavin mononucleotide (FMN) chromophore in phototropin LOVs are
      conserved, supporting the suggestion of their possible role as blue-light
      sensors. The Bacillus subtilis protein YtvA has been the first bacterial LOV
      protein shown to bind FMN and to undergo the same light-induced reactions as
      plant phototropins. The photocycle involves the reversible formation of a
      covalent adduct between FMN and a conserved cysteine. In this work we report
      preliminary results on a Caulobacter crescentus LOV-kinase, that undergoes the
      same photochemistry as YtvA. The bacterial LOV-proteins exhibit a variety of
      effector domains associated to the light-responsive LOV-domain, e.g. histidine
      kinase, transcriptional regulators, putative phosphodiesterases and regulators of
      stress factors, pointing to their physiological role as sensing and signalling
      proteins.

PMID- 15170487
TI  - Functional variations among LOV domains as revealed by FT-IR difference
      spectroscopy.
AB  - The two LOV domains, LOV1 and LOV2, from Chlamydomonas reinhardtii were
      investigated by light-induced FT-IR difference spectroscopy and compared to the
      LOV domain of Bacillus subtilis (YtvA-LOV). It is shown that the two S-H
      conformations of the reactive LOV1 cysteine C57(1) are exposed to environments of
      different hydrogen bonding strength. Thus, the two rotamer configurations of C57
      might be related to the fact that the triplet state decays bi-exponentially into
      the LOV1-390 photoproduct. Exchange of the two other cysteines of LOV1 (C32S and
      C83S) does not alter the S-H stretching band providing evidence that this band
      feature arises solely from C57. The reactive cysteine of LOV2 from Chlamydomonas
      reinhardtii (C250) and of YtvA-LOV (C62) exhibit both a homogenous S-H stretching
      vibrational band which suggests a single conformer of the amino acid side chain.
      Finally, the FT-IR difference spectrum of YtvA from Bacillus subtilis comprising
      the light absorbing LOV domain and the putative signaling STAS (sulfate
      transporter/antisigma-factor antagonist) domain, reveals conformational changes
      in the latter after blue-light excitation.

PMID- 15170488
TI  - The origin of photoactivated adenylyl cyclase (PAC), the Euglena blue-light
      receptor: phylogenetic analysis of orthologues of PAC subunits from several
      euglenoids and trypanosome-type adenylyl cyclases from Euglena gracilis.
AB  - Photoactivated adenylyl cyclase (PAC) is the blue-light receptor flavoprotein
      recently identified as a photoreceptor for photoavoidance of the unicellular
      flagellate, Euglena gracilis. To gain an insight into the evolution of this
      unique protein, similar sequences were searched for in several euglenoids by
      reverse transcriptase-polymerase chain reaction (RT-PCR) using degenerate
      primers. Two similar transcripts were detected in each of the four phototrophic
      euglenoids, Euglena stellata, Colacium sideropus, Eutreptia viridis, Eutreptiella
      gymnastica, and in an osmotrophic (i.e., obtaining nutrients by absorption) one,
      Khawkinea quartana, but not in a phagotrophic euglenoid, Petalomonas cantuscygni.
      Each of them seemed to be orthologous to PACalpha and PACbeta, respectively, and
      had the same domain structure as PAC subunits each of which is composed of two
      flavin binding domains, F1 and F2, each followed by an adenylyl cyclase catalytic
      domain, C1 and C2, respectively. This fact implies that they constitute a
      functional photoactivated adenylyl cyclase like PAC. Phylogenetic analysis of the
      adenylyl cyclase catalytic domains revealed that they belong to a bacterial
      cluster, not to a trypanosomal one. In addition, two trypanosome-type adenylyl
      cyclases were discovered in E. gracilis. In contrast to PAC, deduced amino acid
      sequences of the trypanosome-type adenylyl cyclases indicated that they are
      integral membrane proteins with a membrane spanning region at the midpoint of
      them, followed by an adenylyl cyclase catalytic domain which seems cytoplasmic.
      Overall, we propose that PAC might have been transferred to euglenoids on the
      occasion of secondary endosymbiosis.

PMID- 15170489
TI  - Bacteriophytochrome and regulation of the synthesis of the photosynthetic
      apparatus in Rhodopseudomonas palustris: pitfalls of using laboratory strains.
AB  - The synthesis of the photosynthetic apparatus of different strains of
      Rhodopseudomonas palustris has been studied as a function of the oxygen
      concentration and far-red light. For strain CEA001, only a small amount of
      photosynthetic apparatus is synthesized in the dark for oxygen concentration
      higher than 8% whereas synthesis is strongly enhanced by far-red light
      illumination. This enhancement is due to the action of a bacteriophytochrome
      (ORF2127/ORF2128), which antagonizes the repressor PpsR. On the contrary, a large
      fraction of photosystem is synthesized in the dark and far-red illumination
      induces no enhancement in strain CGA009. This difference in phenotype of strain
      CGA009 is explained by a single point-mutation R428C in the helix-turn-helix DNA
      binding motif of PpsR, rendering it inactive. In addition, a frame-shift mutation
      had occurred in the gene encoding bacteriophytochrome (ORF2127/ORF2128),
      conducting to a truncated inactive sensor. We propose that these mutations
      occurred in culture. Bacteria have developed a sophisticated regulatory process
      to synthesize their photosynthetic apparatus when light is available. This
      process is a critical advantage for the bacteria under natural conditions since
      they optimize their development depending on the available energy resources. On
      the contrary, under laboratory growth conditions where there is no substrate
      limitation, there is no crucial need for such a regulation and deleterious
      mutations affecting this process are of no importance.

PMID- 15170490
TI  - Velocity of chloroplast avoidance movement is fluence rate dependent.
AB  - In Arabidopsis leaves, chloroplast movement is fluence rate dependent. At
      optimal, lower light fluences, chloroplasts accumulate at the cell surface to
      maximize photosynthetic potential. Under high fluence rates, chloroplasts avoid
      incident light to escape photodamage. In this paper, we examine the phenomenon of
      chloroplast avoidance movement in greater detail and demonstrate a proportional
      relationship between fluence rate and the velocity of chloroplast avoidance. In
      addition we show that the amount of light-activated phototropin2, the
      photoreceptor for the avoidance response, likely plays a role in this phenomenon,
      as heterozygous mutant plants show a reduced avoidance velocity compared to that
      of homozygous wild type plants.

PMID- 15170491
TI  - Phytochrome A: functional diversity and polymorphism.
AB  - Phytochrome (phy), a 124 kDa biliprotein, mediates plants' perception of
      environmental light conditions including quantity, quality and duration of light.
      The complex phenomenology of phy function is connected with its polymorphism, the
      major phys being phyA and phyB. PhyA mediates irreversible photoresponses in the
      very low and high fluence ranges (VLFR and HIR) primarily in the far-red (FR)
      spectral region, whereas phyB mediates the 'classical' R/FR reversible responses
      in the low fluence range (LFR). This phyA specificity is determined at the level
      of (i) intramolecular events, (ii) turnover, phyA being light-labile, and (iii)
      nuclear-cytoplasmic partitioning and interaction with partner proteins. A unique
      feature of phyA is that two native isoforms, phyA' and phyA'', comprise it,
      distinguished by spectroscopic and photochemical properties, localization and
      abundance in plant tissues, light stability, and other properties. They differ by
      the post-translational modification at the 6 kDa N-terminus, possibly
      phosphorylation, phyA' being phosphorylated and phyA'' dephosphorylated. Both
      species participate in the light-induced nuclear-cytoplasmic partitioning. The
      light-labile phyA' is responsible for de-etiolation (VLFR and HIR modes), whereas
      the relatively more light-stable phyA'' could be active throughout the whole life
      cycle. PhyA'' interferes with the action of phyA' and this interaction may be
      part of the fine tuning mechanism of the phyA function. Finally, within the phyA'
      pool there are different conformers in thermal equilibrium, that differ by the
      activation and kinetic parameters of the Pr-->lumi-R photoreaction. This
      heterogeneity of phyA may account, at least partially, for the complex dynamics
      of its photoprocesses and the phenomenology of photoresponses.

PMID- 15170492
TI  - PKS1 and PKS2 affect the phyA state in etiolated Arabidopsis seedlings.
AB  - Autophosphorylation of phytochrome A (phyA) and transphosphorylation of its
      reaction partners, phytochrome kinase substrate 1 (PKS1) in particular, might
      play important functions in signal transduction from phyA. It was shown that PKS1
      and PKS2 physically interact with phyA and phyB in vitro, and that overexpression
      of PKS1 interferes with phytochrome signaling in vivo. Moreover, both pks1 and
      pks2 loss of function mutants are specifically defective for one branch of phyA
      signaling. We therefore used in vivo fluorescence spectroscopy to test whether
      mutations in pks1 and pks2 or overexpression of PKS1 (PKS1OX) have an effect on
      phyA and its subpopulations, phyA' and phyA''. It was found that the emission
      spectra of phyA in all the Arabidopsis lines are similar. The phyA content in the
      single mutants pks1 and pks2, and also in PKS1OX, was 1.2-1.5 times higher than
      in the wild type, whereas the phyA'/phyA'' ratio remained practically unchanged
      (approx. 1.0). However, in the double mutant pks1pks2, the picture is reversed-
      the phyA concentration remained unchanged, while the phyA'/phyA'' ratio shifted
      dramatically towards phyA''(0.3). This suggests that (i) the changes in PKS1 or
      PKS2 content may affect the total phyA concentration, (ii) PKS1, together with
      PKS2, could be critical for the formation of phyA', thus shifting the equilibrium
      towards phyA'' in the double mutant and (iii) these variations in the phyA' and
      phyA'' content may contribute to the mutant phenotype of pks1, pks2 and PKS1OX.
      The fact that in the single mutants there are only small changes in the
      phyA'/phyA'' ratio, while in the double mutant the ratio is considerably
      affected, indicates that PKS1 or PKS2 act redundantly with each other in this
      regard.

PMID- 15170493
TI  - Pre-germination seed-phytochrome signals control stem extension in dark-grown
      Arabidopsis seedlings.
AB  - The developmental pattern of dark-grown Arabidopsis thaliana is dramatically
      shifted by exposure of the seedlings to light: inhibition of hypocotyl (stem)
      growth is one of the typical responses. Here, we show that the hypocotyl growth
      of dark-grown seedlings is reduced by exposure of the seeds to light. The light
      signal is perceived by phytochromes A and B during the hours immediately prior to
      seed germination. The effect is obviously selective, as other processes under
      phytochrome control were not equally affected by the pre-germination light cue.
      The hypocotyl response persists for two days after termination of the light
      signal, which is more than the persistence observed when the seedlings themselves
      receive the light stimulus. Treatment with far-red light, which converts
      phytochrome to the inactive form, did not reduce the hypocotyl growth response to
      pre-germination light, indicating that the persistent signal was not active
      phytochrome itself. We propose that trans-developmental phase signals could help
      plants to adjust to their environment.

PMID- 15170494
TI  - Inner retinal photoreceptors (IRPs) in mammals and teleost fish.
AB  - Research over the past decade has provided overwhelming evidence that
      photoreception in the vertebrate eye is not confined to the rods and cones. The
      discovery of non-rod, non-cone ocular photoreceptors in mammals and fish arose
      from quite different lines of investigation. In transgenic mice entirely lacking
      functional rod and cone photoreceptors a range of responses to light, including
      the regulation of the circadian system and a pupillary light reflex, are
      preserved. Electrophysiological and imaging approaches were then able to
      characterise a coupled plexus of directly light sensitive ganglion cells. Most
      recently action spectroscopy has shown that a novel 'blue-light' sensitive
      photopigment based upon opsin/vitamin A (OP480) mediates these responses to
      light. Several candidate genes have emerged for OP480, with melanopsin being by
      far the strongest. A definitive link, however, between this gene and OP480 has
      still to be established. In contrast to the mammals, the discovery of inner
      retinal photoreceptors (IRPs) in fish started with the discovery of a new gene
      family (VA opsin). The teleost VA opsins form functional photopigments and are
      expressed in several different types of inner retinal neuron, including retinal
      horizontal cells. Recent studies have investigated the electrical properties of
      these photosensitive neurones, but their light-sensing role remains a matter of
      speculation. Thus the study of IRP is developing along quite separate lines. In
      the mammals the research is directed towards a molecular identification of the
      photopigment (OP480) and its cascade, whilst in fish the major effort is directed
      towards identifying a role for these novel photoreceptors using physiological
      approaches. The discovery of IRPs in the vertebrates tells us that despite 150
      years of research, we still have much to learn about how the eye processes light.

PMID- 15170496
TI  - Biological photosensors.

PMID- 15170495
TI  - A concept for G protein activation by G protein-coupled receptor dimers: the
      transducin/rhodopsin interface.
AB  - G protein-coupled receptors (GPCRs) are ubiquitous and essential in modulating
      virtually all physiological processes. These receptors share a similar structural
      design consisting of the seven-transmembrane alpha-helical segments. The active
      conformations of the receptors are stabilized by an agonist and couple to
      structurally highly conserved heterotrimeric G proteins. One of the most
      important unanswered questions is how GPCRs couple to their cognate G proteins.
      Phototransduction represents an excellent model system for understanding G
      protein signaling, owing to the high expression of rhodopsin in rod
      photoreceptors and the multidisciplinary experimental approaches used to study
      this GPCR. Here, we describe how a G protein (transducin) docks on to an
      oligomeric GPCR (rhodopsin), revealing structural details of this critical
      interface in the signal transduction process. This conceptual model takes into
      account recent structural information on the receptor and G protein, as well as
      oligomeric states of GPCRs.

PMID- 15170497
TI  - Factors associated with progression to macroalbuminuria in microalbuminuric Type
      1 diabetic patients: the EURODIAB Prospective Complications Study.
AB  - AIMS/HYPOTHESIS: Type 1 diabetic patients who develop microalbuminuria are
      clearly disadvantaged in terms of their risk of morbidity and mortality from
      renal and cardiovascular diseases. It is therefore important to identify
      potential factors that can predict progression to macroalbuminuria. METHODS: This
      is a 7-year follow-up study of 352 microalbuminuric Type 1 diabetic patients from
      31 European centres. Risk factors at baseline were compared in patients who
      progressed to macroalbuminuria and in patients who remained microalbuminuric or
      reverted to normoalbuminuria. Risk factors and albumin excretion rate (AER) were
      measured centrally. RESULTS: Over 7.3 years, 13.9% of the microalbuminuric
      patients progressed to macroalbuminuria, 35.5% remained microalbuminuric and
      50.6% reverted to normoalbuminuria. Independent baseline risk factors for
      progression to macroalbuminuria were HbA(1)c (7.9% vs 6.8%, p=0.004), AER (64.4
      vs 44.9 microg/min, p=0.0001) and-after adjusting for diabetes duration, HbA(1)c
      and AER-body weight (72 vs 67 kg, p=0.05). Independent factors associated with
      regression to normoalbuminuria were diabetes duration (15 vs 18 years, p=0.004),
      AER (37.2 vs 44.9 microg/min, p=0.0001) and-after adjusting for diabetes
      duration, HbA(1)c and AER-waist-to-hip ratio (0.83 vs 0.86, p=0.05) and incidence
      of peripheral neuropathy at baseline (24% vs 38%, p=0.001). Blood pressure and
      smoking did not emerge as risk factors at baseline for the outcome of
      microalbuminuria. CONCLUSIONS/INTERPRETATION: A significant fraction of
      microalbuminuric Type 1 diabetic patients will progress to overt proteinuria.
      Patients with higher AER values, sub-optimal metabolic control, excess body fat
      and peripheral neuropathy may carry a particularly high risk of clinical
      nephropathy requiring aggressive therapeutic intervention.

PMID- 15170499
TI  - Role of the D76N polymorphism of insulin promoter factor-1 in predisposing to
      Type 2 diabetes.

PMID- 15170498
TI  - Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats
      polymorphism in relation to Type 2 diabetes mellitus and insulin release.
AB  - AIMS/HYPOTHESIS: The class III allele of the variable-number-of-tandem-repeats
      polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with
      Type 2 diabetes and altered birthweight. It has also been suggested, although
      inconsistently, that the class III allele plays a role in glucose-induced insulin
      response among NGT individuals. METHODS: We investigated the impact of the class
      III allele on Type 2 diabetes susceptibility in a case-control study involving
      1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the
      potential impact of the class III allele in genotype-quantitative trait studies
      in three Danish study populations containing (i) 358 young healthy subjects; (ii)
      4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT;
      and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes. RESULTS:
      There was no difference in frequency of the class III allele or in genotype
      distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects.
      Among the 358 young subjects the class III/III carriers had significantly reduced
      post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03
      respectively). However, among the 4444 middle-aged subjects we failed to
      demonstrate any association between the class III allele and post-OGTT serum
      insulin and C-peptide levels. CONCLUSIONS/INTERPRETATION: The class III allele of
      the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent
      alterations in glucose-induced insulin release in the examined populations, which
      consisted of Danish Caucasians.

PMID- 15170500
TI  - Unexpected elevation of pentosidine formation in collagen incubated with glucose
      by low concentrations of the AGE-inhibitor aminoguanidine.

PMID- 15170501
TI  - Author reply to Reiger et. al. commentary on Genetic variation of the platelet-
      surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2
      diabetes mellitus.Diabetologia. 2003 Jul;46(7):984-9.

PMID- 15170502
TI  - [Active studies of prostate carcinoma in 2004].

PMID- 15170503
TI  - [Incidence of severe injuries. Results of a population-based analysis].
AB  - It is still unknown exactly how many persons sustain a severe injury (ISS > or
      =16) in Germany each year. Considering the growing restrictions and the
      introduction of DRGs, it was necessary to acquire data about this rather resource
      intensive aspect of trauma care. The aim of this study was therefore to assess
      the incidence of severe trauma within a defined population. In a retrospective
      study all surgical emergencies within a 5-year period (1996-2000) were reviewed.
      Data on type, pattern, severity of injury, and mortality were extracted from the
      patients' records. During the study period 454 persons sustained a severe injury
      (ISS > or =16), 112 individuals died at the scene of the accident, and 64 during
      the hospital stay. The average ISS of the surviving patients was 27 (ISS 16-75).
      The calculated incidence of severe trauma was 25/100,000 inhabitants per year.
      Extrapolated, up to 40,000 persons sustain a severe injury each year in Germany.
      For the first time, this study has provided data on the incidence of major trauma
      in Germany. Based on the acquired data and a previous cost analysis, hospital
      treatment costs for severely injured patients amount to up to 2 billion Euros per
      year in Germany.

PMID- 15170504
TI  - [Fever after travel return].
AB  - Between 20 and 70 percent of the 50 million people who travel from the
      industrialized world to the developing world each year report some illness
      associated with their travel. Approximately 3 percent of people traveling
      internationally for short periods (<2 weeks) report fever even after travel.
      Careful assessment of the travel history, likely incubation period, exposure
      history, associated signs and symptoms, duration of fever, immunization status
      use or nonuse of antimalarial chemoprophylaxis, and degree of compliance with a
      chemoprophylactic regimen, if used, helps to establish the diagnosis. Determining
      an approximate incubation period can be particular helpful in ruling out possible
      causes of fever. Specific examinations targeting the individual infection,
      assumed to be responsible for the development of febrile disease may ascertain
      diagnosis and lead to effective treatment.

PMID- 15170505
TI  - Structure and function of coagulogen, a clottable protein in horseshoe crabs.
AB  - Mammalian blood coagulation is based on the proteolytically induced
      polymerization of fibrinogens. Initially, fibrin monomers noncovalently interact
      with each other. The resulting homopolymers are further stabilized when the
      plasma transglutaminase (TGase) intermolecularly cross-links epsilon-(gamma
      glutamyl)lysine bonds. In crustaceans, hemolymph coagulation depends on the TGase
      mediated cross-linking of specific plasma-clotting proteins, but without the
      proteolytic cascade. In horseshoe crabs, the proteolytic coagulation cascade
      triggered by lipopolysaccharides and beta-1,3-glucans leads to the conversion of
      coagulogen into coagulin, resulting in noncovalent coagulin homopolymers through
      head-to-tail interaction. Horseshoe crab TGase, however, does not cross-link
      coagulins intermolecularly. Recently, we found that coagulins are cross-linked on
      hemocyte cell surface proteins called proxins. This indicates that a cross
      linking reaction at the final stage of hemolymph coagulation is an important
      innate immune system of horseshoe crabs.

PMID- 15170506
TI  - Plant glutaredoxins: still mysterious reducing systems.
AB  - Glutaredoxins are ubiquitous oxidoreductases which are similar to thioredoxins
      and possess a typical glutathione-reducible CxxC or CxxS active site. We present
      here the current knowledge about these proteins in plants. At least 31
      glutaredoxin genes are present in Arabidopsis thaliana, a value close to the
      thioredoxin gene number. Based essentially on active site sequences, a
      classification of these multiple genes is proposed. The specificity of the
      various apparently redundant forms within the glutaredoxin group or between
      glutaredoxin and thioredoxin can be analysed in terms of differential
      spatiotemporal expression of the genes, specificity vs. target proteins and mode
      of catalysis (glutathiolation/ deglutathiolation processes appear to be a
      specific function of glutaredoxin). Additional putative functions are proposed
      for plant glutaredoxins based on their targets in other organisms and in the
      light of the existence of hybrid proteins containing glutaredoxin modules in
      their N- or C-terminal part.

PMID- 15170507
TI  - Mast cell tryptase, a still enigmatic enzyme.
AB  - Tryptases constitute a subfamily of trypsin-like proteinases, stored in the mast
      cell secretory granules of all mammalian organisms. These enzymes are released
      along with other mediators into the extracellular medium upon mast cell
      activation/degranulation. Among the trypsin-like enzymes, tryptases are unique:
      they are present as active enzymes in the mast cell granules, but display
      activity only extracellularly, and have a specificity which is much more
      restricted than trypsin. Tryptases are mostly tetrameric, and in only few
      organisms (not in humans) are they inhibited by endogenous inhibitors in vitro.
      The enzymatic and molecular properties of tryptases are far better characterized
      that any of their plausible biological functions. On the basis of its structural
      and functional features it could be predicted that tryptase would not degrade a
      large number of proteins in vivo due to low accessibility to the tetramer central
      pore where the active sites face inwards. Although their biological function has
      not yet been clarified, tryptases seem to be involved in a number of mast cell
      mediated allergic and inflammatory diseases. In particular, the involvement of
      tryptase in asthma, an inflammatory disease of the airways often caused by
      allergy, has been proposed. Here we review the present knowledge on the structure
      function relationship of tryptases from different organisms, with special
      emphasis on human enzymes, and on their role in a variety of pathophysiological
      processes.

PMID- 15170508
TI  - Regulation of glycosaminoglycan structure and atherogenesis.
AB  - Cardiovascular disease is the major cause of premature death in modern society,
      and its impact is increasing due to rising rates of obesity and type 2 diabetes.
      Clinical studies based on targeting metabolic abnormalities and biomarkers
      demonstrate significant benefits, but always an element of disease remains which
      is resistant to treatment. Recent evidence has strongly implicated an early
      interaction of atherogenic lipoproteins with vascular matrix proteoglycans as the
      initiating step in atherogenesis. Expert commentary has pointed to the need for
      vascular directed therapies to provide reductions in the residual disease
      component. We propose that the regulation of synthesis and thus structure of
      glycosaminoglycans on proteoglycans provides a potential pathway to this
      reduction. We review existing evidence that the vascular synthesis of
      glycosaminoglycan chains can be regulated in a manner which reduces lipoprotein
      binding and the potential application of this strategy to attenuation of the
      current cardiovascular disease pandemic.

PMID- 15170509
TI  - Cytomegalovirus infection blocks apoptosis in cancer cells.
AB  - Recent pathological findings reveal a higher frequency of human cytomegalovirus
      (HCMV) in tumor cells from different tumors compared with surrounding tissues.
      Experimental investigations suggest possible supportive effects of HCMV for tumor
      development and progression. One HCMV effect on tumor cells is the inhibition of
      apoptosis, leading to the promotion of tumor cell survival. Decreased sensitivity
      to treatment-induced tumor cell death is a major reason for failure of anticancer
      chemotherapy. HCMV infection interferes with both the intrinsic and extrinsic
      cellular apoptosis pathways. HCMV promotes cell survival signaling influencing
      the tumor suppressor p53 and its relative p73, and stimulates the antiapoptotic
      Ras/Raf/MEK/Erk- and PI-3K-signaling pathways. Antiapoptotic effects mediated by
      HCMV are inhibited by antiviral treatment in cell culture. Therefore, a better
      understanding of the influence of HCMV infection on tumor cell apoptosis might
      translate into improved anti-cancer therapy.

PMID- 15170510
TI  - Peptide synthesis through evolution.
AB  - Ribosome-catalyzed peptide bond formation is a crucial function of all organisms.
      The ribosome is a ribonucleoprotein particle, with both RNA and protein
      components necessary for the various steps leading to protein biosynthesis.
      Evolutionary theory predicts an early environment devoid of complex biomolecules,
      and prebiotic peptide synthesis would have started in a simple way. A fundamental
      question regarding peptide synthesis is how the current ribosome-catalyzed
      reaction evolved from a primitive system. Here we look at both prebiotic and
      modern mechanisms of peptide bond formation and discuss recent experiments that
      aim to connect these activities. In particular, RNA can facilitate peptide bond
      formation by providing a template for activated amino acids to react and can
      catalyze a variety of functions that would have been necessary in a pre-protein
      world. Therefore, RNA may have facilitated the emergence of the current protein
      world from an RNA or even prebiotic world.

PMID- 15170512
TI  - Annotating proteins from endoplasmic reticulum and Golgi apparatus in eukaryotic
      proteomes.
AB  - The sub-cellular localization of a native protein constitutes one coarse-grained
      aspect of its function. Transport between compartments is often regulated through
      short sequence motifs. Here, we analyzed experimentally characterized endoplasmic
      reticulum (ER)/ Golgi retrieval motifs and investigated the accuracy of homology
      transfer. Only the C-terminal ER retrieval motifs KDEL, HDEL and AIAKE were
      sufficiently specific. However, even unspecific motifs may help, provided we know
      the probability for localization given the motif. We provided such estimates. We
      also rigorously estimated the accuracy and coverage for inferring ER and Golgi
      localization through homology-transfer by sequence similarity. In entire
      proteomes, we could thereby annotate 3304 ER (3182 membrane) and 1853 Golgi (759
      membrane) proteins. We identified another putative 5157 globular and 3941
      membrane ER or Golgi proteins. Each experimental annotation yielded, on average,
      one to three high-accuracy and five to six low-accuracy homology-transfers in the
      six proteomes. These numbers will increase with each new experimental annotation.

PMID- 15170511
TI  - The tumor necrosis factor alpha of the bony fish seabream exhibits the in vivo
      proinflammatory and proliferative activities of its mammalian counterparts, yet
      it functions in a species-specific manner.
AB  - Information on the bioactivities of non-mammalian cytokines is scant due to the
      lack of the recombinant molecules and specific antibodies. We produced the mature
      predicted peptide of tumor necrosis factor alpha (TNF alpha) from the bony fish
      gilthead seabream (Sparus aurata L.) (sbTNF alpha), and its biological role was
      determined in vitro and in vivo. We first demonstrated by analytical size
      exclusion chromatography that sbTNF alpha is an oligomeric protein but the dimer
      appears to predominate over the trimeric form, in contrast to mammalian TNF
      alpha. Intraperitoneal injection of native sbTNF alpha resulted in (i) priming of
      the respiratory burst of the peritoneal exudate and head-kidney (HK) leukocytes,
      the latter being the bone marrow equivalent in fish; (ii) rapid recruitment of
      phagocytic granulocytes to the injection site, and (iii) induction of
      granulopoiesis in the HK. Interestingly, sbTNF alpha was able to induce a strong
      proliferation of HK cells in vitro, whereas human TNF alpha did not. Conversely,
      sbTNF alpha was not cytotoxic for murine L929 fibroblasts.

PMID- 15170513
TI  - Occludin binds to the SH3-hinge-GuK unit of zonula occludens protein 1: potential
      mechanism of tight junction regulation.
AB  - The interaction between tight junction proteins occludin and zona occludens
      protein 1 (ZO-1) was clarified. The sequence cc1 within the hinge region of ZO-1,
      connecting its SH3 and GuK domains, was identified as a new association site for
      the occludin C-terminus, core binding area GLRSSKRNLRKSR (mouse ZO-1(606-618)).
      Occludin also bound to the sequence H2 within GuK, core area HKLRKNNH (ZO-1(759
      766)). In occludin, the binding core was ELSRLDKELDDYREESEEY (mouse occludin(455
      473)). Helicity of the sequences was suggested by circular dichroism. Because
      basic residues in ZO-1, acidic residues in occludin (underlined), coiled-coil
      helix-forming leucine heptad motifs (bold) in occludin and, probably, in cc1 were
      essential, we conclude that interactions were both helical and ionic. Moreover,
      the GuK domain bound other GuK molecules, suggesting oligomerization of ZO-1.
      Generally, the assumption is supported that the SH3-hinge-GuK region represents a
      functional and regulatory unit in ZO-1 forming a multiprotein tight junction
      complex with occludin.

PMID- 15170514
TI  - Modulation of hepatic mitochondrial energy efficiency with age.
AB  - This study was designed to examine the effect of youth-adulthood transition on
      hepatic mitochondrial energy efficiency. The changes in basal and palmitate
      induced proton leak, which contribute to mitochondrial efficiency, were evaluated
      in mitochondria isolated from the liver of young and adult rats. Alterations in
      mitochondrial cytochrome oxidase and aconitase specific activities, and in
      adenine nucleotide translocator content were also assessed. There was no
      difference in basal proton leak or thermodynamic coupling and efficiency of
      oxidative phosphorylation in liver mitochondria between the two rat groups. On
      the other hand, palmitate-induced proton leak increased significantly in adult
      rats. The function of this uncoupling could be avoidance of elevated formation of
      reactive oxygen species, which are known to accelerate ageing.

PMID- 15170515
TI  - Selection and validation of differentially expressed genes in head and neck
      cancer.
AB  - We applied a robust combinatorial (multi-test) approach to microarray data to
      identify genes consistently up- or down-regulated in head and neck squamous cell
      carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal
      tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two
      differentially expressed probe sets (representing 38 genes and one expressed
      sequence tag) satisfied all statistical tests of significance and were selected
      for further validation. Selected probe sets were validated by hierarchical
      clustering, multiple probe set concordance, and target-subunit agreement. In
      addition, real-time PCR analysis of 8 representative (randomly selected from 38)
      genes performed on both microarray-tested and independently obtained samples
      correlated well with the microarray data. The genes identified and validated by
      this method were in comparatively good agreement with other rigorous HNSCC
      microarray studies. From this study, we conclude that combinatorial analysis of
      microarray data is a promising technique for identifying differentially expressed
      genes with few false positives.

PMID- 15170516
TI  - Increased apoptosis in differentiating p27-deficient mouse embryonic stem cells.
AB  - In mouse embryonic stem (mES) cells, the expression of p27 is elevated when
      differentiation is induced. Using mES cells lacking p27 we tested the importance
      of p27 for the regulation of three critical cellular processes: proliferation,
      differentiation, and apoptosis. Although cell cycle distribution, DNA synthesis,
      and the activity of key G1/S-regulating cyclin-dependent kinases remained
      unaltered in p27-deficient ES cells during retinoic acid-induced differentiation,
      the amounts of cyclin D2 and D3 in such cells were much lower compared with
      normal mES cells. The onset of differentiation induces apoptosis in p27-deficient
      cells, the extent of which can be reduced by artificially increasing the level of
      cyclin D3. We suggest that the role of p27 in at least some differentiation
      pathways of mES cells is to prevent apoptosis, and that it is not involved in
      slowing cell cycle progression. We also propose that the pro-survival function of
      p27 is realized via regulation of metabolism of D-type cyclin(s).

PMID- 15170518
TI  - Y-type urethral duplication: an unusual variant of a rare anomaly.
AB  - Urethral duplications are rare anomalies. We present a 3-year-old continent boy
      passing urine since birth per anus while voiding from penis. Micturating
      cystourethrogram, retrograde urethrogram and cystoscopy revealed a Y connection
      between the posterior urethra and anal canal. The accessory channel was excised
      by a perineal approach. Histopathology revealed that the tract was lined by
      transitional epithelium, proving that it was indeed a case of urethral
      duplication; hence, we suggest that all urethroanal fistulas are not variants of
      anorectal malformations. Certain of these fistulas should be considered as
      variants of Y-type urethral duplication even if the orthotopic urethra is normal.

PMID- 15170517
TI  - Open versus closed day-case haemorrhoidectomy: is there any difference? Results
      of a prospective randomised study.
AB  - BACKGROUND AND AIMS: Nowadays there is still controversy as to whether open or
      closed haemorrhoidectomy is the surgical treatment of choice for haemorrhoidal
      pathology. PATIENTS AND METHODS: We carried out a randomised prospective study in
      the Day Surgery Unit comparing 100 patients undergoing Milligan-Morgan
      haemorrhoidectomy (group A) versus 100 patients undergoing Ferguson
      haemorrhoidectomy (group B) for symptomatic haemorrhoids, in whom medical
      treatment or rubber band ligation had failed. RESULTS: Characteristics of the
      population were: mean age 43.5 years, with predominance of males, 123 vs. 77; 88%
      ASA I-II. CLINICAL PRESENTATION: 95% rectal bleeding; 87.5% third-fourth degree.
      The anaesthetic technique of choice was local anaesthesia plus sedation in 180
      patients (90%). Length of surgery: 24 min (group A) and 30 min (group B)
      (p=n.s.). Resection of three haemorrhoidal cushions was done in 87.5% of cases.
      There were no re-operations or re-admissions after discharge. Symptomatic
      recurrence, stenosis and incontinence were not found during the follow-up of the
      first year. Postoperative pain during the first postoperative week was greater in
      the open haemorrhoidectomy group, but the difference was statistically
      significant (p<0.05) only during bowel movements. There was complete healing in
      40% of the patients in group A and 90% of those in group B (p<0.05) after 1
      month. After 1 year, the results and complications were similar in both groups
      (p=n.s.). CONCLUSIONS: Closed haemorrhoidectomy gives better results in terms of
      pain and healing than open haemorrhoidectomy, whereas recurrence and
      complications are similar after 1 year.

PMID- 15170520
TI  - Annual variations of adrenal gland hormones in the lizard Podarcis sicula.
AB  - The adrenal gland regulates metabolism and maintains normal electrolyte balance.
      Adrenal hormones are equivalent in all vertebrates; the chromaffin tissue
      produces adrenaline and noradrenaline and the steroidogenic tissue produces most
      of the steroid hormones present in mammals. Podarcis sicula belongs to the
      Squamata family of lizards and it is the most abundant lizard species in southern
      Italy. This species shows a reproductive annual cycle and the presence of
      seasonal variations in the activity of the hypothalamus-hypophyseal-thyroid axis.
      To investigate the existence of an annual cycle of lizard adrenal gland, we have
      measured plasma concentrations of corticosterone, ACTH, noradrenaline and
      adrenaline. We have shown that corticosterone rapidly increased from January to
      March to reach a peak value that persisted until July, then, it slowly decreased
      until December. ACTH levels increased from January to May and slowly decreased
      from July to December. Noradrenaline levels were higher in March and then
      decreased until December. On the contrary, adrenaline levels increased from March
      to July and slowly decreased until December. Our results demonstrate the
      existence of an annual cycle of the lizard adrenal gland activity. This is very
      interesting because its activity is important to rightly regulate the
      reproductive status of the Podarcis sicula lizard.

PMID- 15170521
TI  - No predictive value of cytotoxic or helper T-cell precursor frequencies for
      outcome when analyzed from the graft after stem cell transplantation.
AB  - The predictive value of limiting dilution analyses (LDA) measuring cytotoxic and
      helper T-lymphocyte precursor (CTLp and HTLp) frequencies for outcome after stem
      cell transplantation (SCT) is still a matter of debate. One reason may be that
      CTLp and HTLp frequencies are determined in peripheral blood mononuclear cells
      (PBMC) and this responder cell population does not reflect the cell type
      composition of the graft. We assessed whether CTLp and HTLp LDA can predict
      complications after human leukocyte antigen (HLA)-identical SCT when CTLp and
      HTLp frequencies are analyzed in PBMC of the respective stem cell graft [bone
      marrow (BMMC) or granulocyte colony-stimulating factor (G-CSF)-mobilized PBMC]
      and compared to PBMC of PB. Host-specific CTLp frequencies measured in 25
      patients and HTLp frequencies analyzed in 6 patients were low in all responder
      cell sources. CTLp and HTLp frequencies seen against HLA-mismatched unrelated
      third-party cells were high, but third-party-specific CTLp and HTLp frequencies
      were lower in G-CSF-PBMC than in PBMC ( p=0.047 for CTLp frequencies). Host
      specific CTLp frequencies analyzed in all responder cell sources did not predict
      acute or chronic graft-versus-host disease (GVHD). Lower CTLp frequencies were
      detected in all responder cell sources from patients who relapsed after SCT than
      in patients without relapse, but the differences between both groups were
      statistically significant only in PBMC. In conclusion, a significant correlation
      was detected only between relapse and CTLp frequencies measured in PBMC. The
      lower frequency of third-party-specific cells in G-CSF-PBMC indicates that the
      mobilization procedure with G-CSF itself may influence results.

PMID- 15170523
TI  - Biodegradation of hydrocarbon cuts used for diesel oil formulation.
AB  - The biodegradability of various types of diesel oil (DO), such as straight-run
      DO, light-cycle DO, hydrocracking DO, Fischer-Tropsch DO and commercial DO, was
      investigated in biodegradation tests performed in closed-batch systems using two
      microflorae. The first microflora was an activated sludge from an urban
      wastewater treatment plant as commonly used in biodegradability tests of
      commercial products and the second was a microflora from a hydrocarbon-polluted
      soil with possible specific capacities for hydrocarbon degradation. Kinetics of
      CO(2) production and extent of DO biodegradation were obtained by chromatographic
      procedures. Under optimised conditions, the polluted-soil microflora was found to
      extensively degrade all the DO types tested, the degradation efficiencies being
      higher than 88%. For all the DOs tested, the biodegradation capacities of the
      soil microflora were significantly higher than those of the activated sludge.
      Using both microflora, the extent of biodegradation was highly dependent upon the
      type of DO used, especially its hydrocarbon composition. Linear alkanes were
      completely degraded in each test, whereas identifiable branched alkanes such as
      farnesane, pristane or phytane were degraded to variable extents. Among the
      aromatics, substituted mono-aromatics were also variably biodegraded.

PMID- 15170522
TI  - Bone marrow transplantation for therapy-related acute myeloid leukemia in
      congenital retinoblastoma associated with 13q deletion syndrome.
AB  - Children with constitutional deletion of the long arm of chromosome 13 are at
      risk for retinoblastoma (RB) due to loss of the RB tumor suppressor gene. The
      prognosis is poor since the tumors are often bilateral, aggressive, and recurrent
      and the patients often harbor other congenital abnormalities. One further
      complication is that of therapy-related malignancies later in life. We report a
      case of allogeneic stem cell transplantation for therapy-related acute myeloid
      leukemia in an 8-year-old girl after multimodality treatment for refractory
      bilateral relapsing RB, with excellent outcome in both the ophthalmic and marrow
      disease.

PMID- 15170524
TI  - Classically conditioned postural reflex in cerebellar patients.
AB  - The aim of the current study was to compare postural responses to repetitive
      platform-evoked perturbations in cerebellar patients with those of healthy
      subjects using a classical conditioning paradigm. The perturbations consisted of
      tilting of the platform (unconditioned stimulus: US) at random time intervals,
      preceded by an auditory signal that represented the conditioning stimulus (CS).
      Physiological reactions were recorded biomechanically by measuring the vertical
      ground forces, yielding the center of vertical pressure (CVP), and
      electrophysiologically by EMG measurements of the main muscle groups of both
      legs. The recording session consisted of a control section with US-alone trials,
      a testing section with paired stimuli and a brief final section with US-alone
      trials. Healthy control subjects were divided into those establishing conditioned
      responses (CR) in all muscles tested (strategy I) and those with CR in the
      gastrocnemius muscles only (strategy II), suggesting an associative motor-related
      process is involved. Patients with a diffuse, non-localized disease were almost
      unable to establish CR. This was also true for a patient with a focal surgical
      lesion with no CR on the affected side but who, simultaneously, showed an
      essentially normal CR incidence on the intact side. During US-alone trials
      healthy controls exhibited a remarkable decay of the UR amplitude due to a non
      associative motor-related process such as habituation. The decay was most
      prominent in the paired trials section. In contrast, patients showed no
      significant differences in the UR amplitude throughout the entire recording
      session. Analysis of the CVP supported the electrophysiological findings, showing
      CR in the controls only. The differences between the responses of control
      subjects and those of the cerebellar patients imply strongly that the cerebellum
      is involved critically in controlling associative and non-associative motor
      related processes.

PMID- 15170525
TI  - Retrospective detection of exposure to nerve agents: analysis of
      phosphofluoridates originating from fluoride-induced reactivation of phosphylated
      BuChE.
AB  - The utility was explored of a new approach to detect retrospectively exposure to
      nerve agents by means of conversion of the inhibitor moiety bound to the active
      site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate
      which is subsequently analyzed by means of gas chromatography (GC). This
      quantifies >or=0.01% inhibition of BuChE and identifies the structure of the
      inhibitor except for the original leaving group. A three-tiered approach was
      followed involving the five classical nerve agents GA, GB, GF, GD, and VX, as
      well as the active metabolite of parathion, i.e., paraoxon: in vivo experiments
      in rhesus monkeys after iv administration of a sign-free dose of agent and
      concomitant in vitro experiments in plasma of rhesus monkeys and humans should
      allow an assessment of in vivo retrospectivity in humans. A systematic
      investigation was performed in order to find a single set of reaction conditions
      which yields a maximum amount of phosphofluoridate for all nerve agents. Fluoride
      induced reactivation at 25 degrees C at a final concentration of 250 mM KF during
      15 min in a pH-range between 4 and 6 appears to be effective. The in vitro
      decrease with time in reactivatibility of inhibited BuChE in plasma from humans
      and rhesus monkeys was largely due to aging of the phosphyl moiety, except for VX
      where spontaneous reactivation was a major cause. The decrease followed first
      order except for a biphasic course in the case of GF in human and rhesus monkey
      plasma as well as of GD in rhesus plasma. In vitro half-lifes in human plasma
      ranged between ca. 14 h for GB and ca. 63 h for GA. A comparison of the in vivo
      data from rhesus monkeys and the in vitro data is complicated by the observation
      that the in vivo decrease with time of fluoride-reactivated phosphofluoridate is
      biphasic for all nerve agents. The terminal in vivo phase pertains to a small
      fraction of the amount of initially regenerated phosphofluoridate but is
      responsible for a considerable degree of retrospectivity, ranging between 14 and
      56 days for GF and GB, respectively. The new procedure can be used in a variety
      of practical applications, e.g., (i) biomonitoring in health surveillance at
      exposure levels that are several orders of magnitude lower than presently
      possible; (ii) diagnosis in case of alleged exposure to nerve agents in time of
      war or after terrorist attacks; (iii) in forensic cases against suspected
      terrorists that have handled organophosphate anticholinesterases; and (iv) in
      research applications such as investigations on lowest observable effect levels
      of exposure to nerve agents.

PMID- 15170526
TI  - Animal testing and alternative approaches for the human health risk assessment
      under the proposed new European chemicals regulation.
AB  - During the past 20 years the EU legislation for the notification of chemicals has
      focussed on new chemicals and at the same time failed to cover the evaluation of
      existing chemicals in Europe. Therefore, in a new EU chemicals policy (REACH,
      Registration, Evaluation and Authorization of Chemicals) the European Commission
      proposes to evaluate 30,000 chemicals within a period of 15 years. We are
      providing estimates of the testing requirements based on our personal experiences
      during the past 20 years. A realistic scenario based on an in-depth discussion of
      potential toxicological developments and an optimised "tailor-made" testing
      strategy shows that to meet the goals of the REACH policy, animal numbers may be
      significantly reduced below 10 million if industry would use in-house data from
      toxicity testing, which are confidential, if non-animal tests would be used, and
      if information from quantitative structure activity relationships (QSARs) would
      be applied in substance-tailored testing schemes. The procedures for evaluating
      the reproductive toxicity of chemicals have the strongest impact on the total
      number of animals bred for testing under REACH. We are assuming both an active
      collaboration with our colleagues in industry and substantial funding of the
      development and validation of advanced non-animal methods by the EU Commission,
      specifically in reproductive and developmental toxicity.

PMID- 15170527
TI  - Retransplantation of the liver in adults: outcome and predictive factors for
      survival.
AB  - Hepatic retransplantation is considered to carry a higher risk than primary
      transplantation. Survival might improve with more experience and better
      immunosuppression. We studied all 55 patients who were adults at the time of
      their first retransplantation and who underwent retransplantation between 1979
      and May 2001. Patient survival at 1, 5 and 10 years was 73%, 63%, and 63%,
      respectively. Multivariate analysis of pre-transplant variables revealed
      prothrombin time, creatinine level, and indication for retransplantation, as
      independent predictive factors. Survival was highest in patients who had
      undergone retransplantation for hepatic artery thrombosis. Multivariate analysis,
      including pre-, per-, and post-operative variables, showed that era of
      transplantation, prothrombin time, blood loss, and intensive care unit (ICU)
      stay, were independent predictive factors. Survival at 1 and 5 years improved
      from 56% and 48%, respectively, before 1996 to 89% and 81%, respectively, after
      1996. In conclusion, survival after hepatic retransplantation improved
      significantly through the years. Independent pre-transplant predictive factors
      were prothrombin time, creatinine level, and indication for retransplantation.

PMID- 15170529
TI  - Respiratory physiotherapy vs. suction: the effects on respiratory function in
      ventilated infants and children.
AB  - OBJECTIVE: To assess and compare the effects of physiotherapy and suction on
      expired tidal volume (V(TE)), respiratory compliance (C(rs)), resistance (R(rs))
      and arterial blood gases. DESIGN: Randomised cross-over study comparing outcomes
      after both treatments on the same day. SETTING: Intensive tertiary care units,
      Great Ormond Street Hospital, London. PATIENTS: One hundred children on full
      ventilatory support requiring physiotherapy. Paired measurements were obtained in
      90 participants, and 7 others were excluded because of tracheal tube leak.
      INTERVENTIONS: Respiratory physiotherapy and suction. MEASUREMENTS AND RESULTS:
      Physiotherapy lasted longer and required more saline and catheters per treatment.
      There were no significant group changes in V(TE) or C(rs) after either treatment,
      but a tendency for R(rs )to fall following physiotherapy which reached
      significance in patients on volume-preset ventilation. There were also small but
      statistically significant reductions in HCO(3)(-), base excess and SaO(2) after
      physiotherapy. V(TE) and C(rs) increased and R(rs) decreased in excess of their
      95% limits of agreement for normal variability in approximately twice as many
      subjects following physiotherapy than suction, these differences being
      significant for V(TE) and approaching significance for C(rs) and R(rs).
      CONCLUSIONS: Physiotherapy appeared to have an advantage in reducing R(rs )in
      some patients, but also produced changes in derived blood gas parameters. Within
      individuals, physiotherapy treatments were also more likely to produce
      improvements in V(TE), C(rs) and R(rs) than suction. Further research should
      identify sensitive patient selection criteria and assess longer-term effects of
      such treatments.

PMID- 15170530
TI  - Correlation between pollen morphology and pollination mechanisms in the
      Hydrocharitaceae.
AB  - The pollen morphology of 11 genera and 11 species of the Hydrocharitaceae and one
      species of the Najadaceae was studied using scanning and transmission electron
      microscopies, and the exine structures and sculptures are discussed in relation
      to pollination mechanisms and the molecular phylogeny. The pollen grains of the
      Hydrocharitaceae are spherical, inaperturate, and form monads or tetrads, while
      those of the Najadaceae are elliptical, inaperturate, and form monads. The
      entomophilous genera Egeria, Blyxa, Ottelia, Stratiotes, and Hydrocharis share
      pollen grains that have projections like spines or bacula. The anemophilous genus
      Limnobium has reticulate pollen grains. The hypohydrophilous genera Thalassia and
      Najas are characterized by pollen grains with reduced exine structures. The
      pollen-epihydrophilous genera Elodea and Hydrilla have tightly arranged small
      spinous pollen grains, and the male flower-epihydrophilous genera Enhalus and
      Vallisneria have reduced reticulate or gemmate exines. Character state
      reconstruction of the exine structures and sculptures using a molecular
      phylogenetic tree suggests that variation in the exine is generally correlated
      with the pollination mechanism; the selective pressures acting on the pollination
      mechanisms have reduced the exine structure in hypohydrophilous plants and
      resulted in various exine sculptures that are adapted to the different
      pollination mechanisms in entomophilous, anemophilous, and pollen-epihydrophilous
      plants.

PMID- 15170528
TI  - Year in review in Intensive Care Medicine-2003. Part 1: Respiratory failure,
      infection and sepsis.

PMID- 15170531
TI  - Effect of the concentration of magnetic grains on the linear-optical-absorption
      coefficient of ferrofluid-doped lyotropic mesophases: deviation from the Beer
      Lambert law.
AB  - In this paper is reported a systematic experimental study of the linear-optical
      absorption coefficient of ferrofluid-doped isotropic lyotropic mixtures as a
      function of the magnetic-grains concentration. The linear optical absorption of
      ferrolyomesophases increases in a nonlinear manner with the concentration of
      magnetic grains, deviating from the usual Beer-Lambert law. This behavior is
      associated to the presence of correlated micelles in the mixture which favors the
      formation of small-scale aggregates of magnetic grains (dimers), which have a
      higher absorption coefficient with respect to that of isolated grains. We propose
      that the indirect heating of the micelles via the ferrofluid grains
      (hyperthermia) could account for this nonlinear increase of the linear-optical
      absorption coefficient as a function of the grains concentration.

PMID- 15170533
TI  - Force between unlike star-polymers versus the solvent quality.
AB  - We re-examine here the computation of the effective force between two star
      polymers A and B of different chemical nature, which are immersed in a common
      solvent. This force originates from the excluded-volume interactions and chemical
      segregation. We assume that the solvent quality may be different for the two
      unlike star-polymers, that is the solvent can be 1) a good solvent for A and B,
      2) a good solvent for A and a Theta-solvent for B, or 3) a Theta-solvent for the
      two polymers. The purpose is a quantitative study of the effect of the solvent
      quality on the effective force, which is a function of the center-to-center
      distance. Calculations are achieved using the renormalization theory applied to
      the Edwards continuous model. We first show that, when the mutual interactions
      are present, the effective force decays as the inverse of distance, but with a
      universal amplitude depending on the solvent quality. Second, we demonstrate the
      existence of three kinds of forces related to situations 1), 2) and 3) described
      above, and give the third-order epsilon-expansions (epsilon = 4 - d, 4 is the
      critical dimension) of the corresponding amplitudes. These series can be resummed
      using the Borel-Leroy techniques to obtain the best three-dimensional values for
      the expected force amplitudes. Finally, this work must be regarded as a natural
      extension of a published one which dealt with the same problem, but where the
      solvent was assumed to be good for the two unlike star-polymers.

PMID- 15170532
TI  - Effects of counterion fluctuations in a polyelectrolyte brush.
AB  - We investigate the effect of counterion fluctuations in a single polyelectrolyte
      brush in the absence of added salt by systematically expanding the counterion
      free energy about Poisson-Boltzmann mean-field theory. We find that for strongly
      charged brushes, there is a collapse regime in which the brush height decreases
      with increasing charge on the polyelectrolyte chains. The transition to this
      collapsed regime is similar to the liquid-gas transition, which has a first-order
      line terminating at a critical point. We find that, for monovalent counterions,
      the transition is discontinuous in theta solvent, while for multivalent
      counterions, the transition is generally continuous. For collapsed brushes, the
      brush height is not independent of grafting density as it is for osmotic brushes,
      but scales linear with it.

PMID- 15170534
TI  - Exact effective force between star-polymers in a Theta-solvent.
AB  - We re-examine here the computation of the effective force between two star
      polymers of respective numbers of branches f(1) and f(2), immersed in a common
      Theta-solvent. Such a force originates essentially from the repulsive three-body
      interactions. To achieve this, we take advantage of some established results
      using renormalization theory for three-dimensional star-polymers, or conformal
      invariance for two-dimensional ones. We first show that, in dimension d = 3, the
      force, F(r), decreases with the center-to-center distance r as F(r)/kappa BT
      congruent with Af1f2 x [r ln (R2/r2]-1 (r<R), with the exact universal amplitude
      Af1f2 = f1f2(f1 + f2 - 2)/22. Second, in dimension d = 2, we find that the force
      decays more slowly as F(r)/kappa BT congruent with Bf1f2 x r-1 (r<R), with the
      exact universal amplitude Bf1f2. For high distances compared to the gyration
      radius, R approximately a square root of N, of a single polymer chain at the
      Theta-point, an exponential decay of the force is expected.

PMID- 15170535
TI  - Finite-size effects do not reduce the repeat spacing of phospholipid multibilayer
      stacks on a rigid substrate.
AB  - Finite-size effects in stacks of phospholipid bilayers, in the fluid L alpha
      phase, are investigated using samples oriented on silicon substrates. Recently in
      this journal, such effects have been suggested as the probable cause of reduced
      lamellar repeat spacings in very thin samples made up of a few (<10) bilayers.
      Our systematic studies on samples of different thicknesses do not support this
      conclusion. At full hydration all samples are found to have the same repeat
      spacing, irrespective of their thickness. At lower hydrations, on the other hand,
      very thin samples, consisting of only a few bilayers, have a slightly larger
      spacing.

PMID- 15170536
TI  - Exploring the melting of a semirigid-chain polymer with temperature-resolved
      small-angle X-ray scattering.
AB  - The thermal behavior of semirigid semicrystalline polymers differs significantly
      from that of flexible-chain polymers. The origin of the differences is believed
      to lie in the higher energy expenditure associated with the formation of adjacent
      re-entry folds at the crystalline surface in the case of semirigid chains. The
      effect of constraints imposed by the interlamellar amorphous regions on the
      neighboring crystals was studied with temperature-resolved synchrotron radiation
      small-angle X-ray scattering (SAXS). The analysis of SAXS patterns with a
      generalized paracrystalline lamellar stack model indicates that melting of a
      semirigid-chain polymer is not a random process but that the crystals grown in
      the smallest amorphous gaps melt first. This suggests that the hitherto largely
      neglected geometrical confinement effects may play an important role in
      determining the thermodynamic stability of semirigid-chain polymer crystals.

PMID- 15170537
TI  - Membranes with rotating motors: microvortex assemblies.
AB  - We study collections of rotatory motors confined to 2-dimensional manifolds. The
      rotational motion induces a repulsive hydrodynamic interaction between motors
      leading to a non-trivial collective behavior. For high rotation speed, motors
      should arrange on a triangular lattice exhibiting crystalline order. At low
      speed, they form a disordered phase where diffusion is enhanced by velocity
      fluctuations. In confining geometries and under suitable boundary conditions,
      motor-generated flow might enhance left-right symmetry-breaking transport. All
      these effects should be experimentally observable for motors driven by external
      fields and for dipolar biological motors embedded into lipid membranes in a
      viscoelastic solvent.

PMID- 15170538
TI  - Inter-lamellar interactions modulated by addition of guest components.
AB  - We have investigated the effects of a guest component (polymer or spherical
      colloidal particle) confined between flexible lamellar slits on the inter
      lamellar interaction by means of a small-angle X-ray scattering technique and a
      neutron spin echo technique. The dominant interaction between flexible lamellar
      membranes without guest components is the Helfrich mechanism. The addition of a
      neutral polymer into the lamellar phase induces an attractive inter-lamellar
      interaction and finally destabilizes the lamellar phase. On the other hand,
      spherical colloidal particles confined between flexible lamellar membranes reduce
      the undulational fluctuations of lamellae and bring a repulsive inter-lamellar
      interaction. The behavior of the layer compression modulus of the lamellar
      membrane containing colloidal particles is well described by the entropical
      repulsive inter-lamellar interaction driven by steric hindrance.

PMID- 15170539
TI  - Enhancement of the orientational order parameter of nematic liquid crystals in
      thin cells.
AB  - Abstract. We report measurements of birefringence (Delta n) of several nematic
      liquid crystals having transverse as well as longitudinal dipole moments in thin
      (1.4 to 2.3 microm) and thick (7 to 16 microm) cells. Rubbed polyimide-coated
      glass plates are used to get planar alignment of the nematic director in these
      cells. We find significant enhancement (6 to 18%) of Delta n (proportional to S,
      where S is the orientational order parameter) in thin cells in all compounds with
      aromatic cores even at temperatures far approximately 20 degrees C) below the
      nematic-isotropic transition point. The enhancement is larger in compounds having
      several phenyl rings and lower if the number of phenyl rings is reduced. In a
      compound that does not have an aromatic core no significant enhancement is
      observed, implying that the strength of the surface potential depends on the
      aromaticity of the cores. Assuming a perfect orientational order at the surface,
      calculations based on the Landau-de Gennes theory show that the thickness
      averaged enhancement of S is sharply reduced as the temperature is lowered in the
      nematic phase. The measured order parameter S is further enhanced in thin cells
      because of the stiffening of the elastic constant which reduces the thermal
      fluctuations of the nematic director. The combined effect is however too small at
      low temperatures to account for the experimental data.

PMID- 15170540
TI  - The interfacial energy of two-dimensional bidisperse cellular fluids.
AB  - Abstract. The mixing energy of two biphasic fluid systems (dispersions of two
      liquids or a liquid and a gas, A and B in a liquid C), confined between two
      parallel plates, is calculated. Our attention is limited to concentrated and
      monodisperse systems, i.e. emulsions and foam/emulsions consisting of equal-size
      (if of the same composition) cells separated by a thin liquid film. It is
      demonstrated that the multiphase mixtures ordered into regular patterns can be
      stable in a wide range of interfacial tensions acting along A-C and B-C
      interfaces and also in a wide range of volume fractions of fluid A. Anisotropic
      properties of such well-ordered structures are also demonstrated.

PMID- 15170543
TI  - Accuracy of preoperative pinhole subtraction single photon emission computed
      tomography for patients with primary and recurrent hyperparathyroidism in an
      endemic goiter area.
AB  - PURPOSE: Bilateral parathyroid exploration is still the standard therapeutic
      procedure for primary and recurrent hyperparathyroidism (HPTH). Since a
      unilateral surgical strategy that reduces surgical complications should not
      increase the risk of missing enlarged parathyroid glands, reliable preoperative
      imaging is the first requirement for this approach. This study was conducted to
      assess the accuracy of preoperative (99m)TcO(4)-(201)T1 pinhole subtraction
      single photon emission computed tomography (SPECT) compared with sonography.
      METHODS: The study population consisted of 15 patients with primary (n = 13) or
      recurrent (n = 2) HPTH who underwent preoperative (99m)TcO(4)-(201)T1 pinhole
      subtraction SPECT. Preoperative sonography was also done in 14 of these patients.
      RESULTS: (99m)TcO(4)-(201)T1 pinhole subtraction SPECT was significantly more
      accurate than sonography. It had an overall accuracy of 80% in detection of
      enlarged parathyroid glands. The accuracy of localization increased to 92.3% in
      patients with solitary adenomas, and to 100% in those with solitary adenomas and
      no previous parathyroid exploration. CONCLUSIONS: The high accuracy of
      preoperative localization with (99m)TcO(4)-(201)T1 pinhole subtraction SPECT in
      patients with primary and recurrent HPTH allows for an imaging-guided unilateral
      operative strategy in most patients, even those with concomitant nodular goiters.
      This may reduce the risk of surgical complications and expand the use of
      minimally invasive techniques in parathyroid surgery.

PMID- 15170542
TI  - RET oncogene expression of papillary thyroid carcinoma in Korea.
AB  - PURPOSE: To identify the prevalence of RET/PTC oncogene expression in Korea, and
      to investigate the correlation between RET/PTC oncogene expression and the known
      prognostic factors of papillary thyroid carcinoma (PTC) in 22 patients. METHODS:
      We performed reverse transcription-polymerase chain reaction (RT-PCR) for
      RET/PTC1, RET/PTC2, and RET/PTC3 rearrangements and immunohistochemical staining
      for the RET gene. Patient information was obtained from medical records. The
      chi(2) test, independent sample t-test, and logistic regression were used for
      statistical analysis. RESULTS: The mean age of the patients was 44.4 years.
      RET/PTC rearrangement by RT-PCR was positive in only 2 (9.1%) of the 22 patients,
      and RET/PTC1 and RET/PTC3 were positive in 1 patient each (4.5%).
      Immunohistochemical staining revealed positive RET oncogene expression in 8
      patients (36.3%). RET oncogene expression was marginally related to recurrence (
      P = 0.05), but without significance by multivariate analysis. CONCLUSION: It is
      possible that a rare form of rearrangement exists in Korean papillary thyroid
      carcinoma, but this study failed to prove that RET oncogene expression is
      associated with alleged prognostic factors.

PMID- 15170544
TI  - Division of the pulmonary ligament after upper lobectomy is less effective for
      the obliteration of dead space than leaving it intact.
AB  - PURPOSE: To investigate whether division of the pulmonary ligament after upper
      lobectomy obliterates dead space. METHODS: Thirty-five patients scheduled to
      undergo upper lobectomy (23 right, 12 left) were randomly assigned to two groups,
      according to whether the inferior pulmonary ligament was divided (11 right, 12
      left) or preserved (6 right, 6 left). To assess upward movement of the
      nonoperated lobes, plain chest X-ray films (posterior-anterior) were done at end
      inspiration preoperatively and 1 month postoperatively, and the ratio of dead
      space in the longitudinal axis was measured. To assess the change in the angle of
      the main bronchus, chest X-ray tomography films were done preoperatively and 1
      month postoperatively. The angles formed by the main bronchus and the truncus
      intermedius on the right side, and by the main bronchus and the lower bronchus on
      the left side, were measured, and the postoperative changes were calculated.
      RESULTS: The dead space ratio did not differ significantly between the divided
      group and the preserved group (3.5% vs 5.5%) or between sides. The change in the
      angle of the main bronchus did not differ significantly between the two groups on
      either the right (36.4 degrees vs 36.3 degrees) or the left side (72.5 degrees vs
      60.0 degrees). CONCLUSION: Division of the pulmonary ligament after upper
      lobectomy is less effective for the obliteration of dead space than leaving it
      intact.

PMID- 15170545
TI  - Cerebral perfusion during off-pump coronary artery bypass grafting.
AB  - PURPOSE: It is still unclear whether cerebral perfusion is affected during off
      pump coronary bypass grafting (OPCABG). We investigated the predictive value of
      the neurobiochemical markers of brain damage and cerebral perfusion in relation
      to early neuropsychological outcome after OPCABG. METHODS: We performed OPCABG in
      ten patients (mean age, 63.4 +/- 5.5 years). A 5.5 F oximetric catheter was
      placed in the jugular bulb to continuously measure jugular oxygen saturation
      (SjO(2)) during OPCABG. We also examined the activity of daily living (ADL) index
      and performed the Mini-Mental State Examination (MMSE) to assess
      neuropsychological state preoperatively and 7 days postoperatively. Venous serum
      levels of neuron-specific enolase (NSE) and brain-specific creatine kinase (CK
      BB) were measured preoperatively and 24 h after skin closure. RESULTS: The mean
      arterial blood pressure and the SjO(2) during anastomosis of the left circumflex
      coronary artery (Cx) were significantly lower than that of the left anterior
      descending coronary artery (LAD) (P < 0.001). None of the patients died. There
      was no transient or permanent neurologic deficit. Cognitive decline was evident
      in two patients with a low SjO(2) and a high postoperative NSE level. The
      postoperative CK-BB value was normal in all patients. CONCLUSIONS: Monitoring
      intraoperative continuous cerebral oxygen desaturation and postoperative NSE
      levels could be useful for predicting early neuropsychological outcome after
      OPCABG.

PMID- 15170546
TI  - Laparoscopic Nissen fundoplication for gastroesophageal reflux disease in Japan.
AB  - PURPOSE: Laparoscopic antireflux surgery is the standard treatment for
      gastroesophageal reflux disease (GERD) in Western countries where this disorder
      is common; however, it has only recently been introduced in Japan. We examined
      the effectiveness of laparoscopic antireflux surgery in a small series of
      Japanese patients. METHODS: Between 1998 and 2001 we performed laparoscopic
      Nissen fundoplication in 23 patients to evaluate the efficiency of this
      technique. We examined the following four parameters pre- and postoperatively:
      symptoms, endoscopic findings, gastroesophagogram findings, and the results of
      intraesophageal 24-h pH monitoring. We also examined the operation time, blood
      loss, intraoperative complications, and postoperative complications. RESULTS: The
      operation was safely performed in all patients, regardless of age, and there were
      no intraoperative complications. Postoperatively, more than three parameters were
      effectively normalized in 17 (89.5%) of 19 patients. The only postoperative
      complications were delayed gastric emptying in three patients and persistent
      dysphagia in five patients. During follow-up, esophagitis recurred in two
      patients, one of whom underwent laparoscopic refundoplication, which normalized
      the condition. CONCLUSION: Laparoscopic Nissen fundoplication is highly effective
      for GERD and could become the standard surgical treatment in Japan.

PMID- 15170547
TI  - Long-term results of high-dose extracorporeal and endocavitary radiation therapy
      followed by abdominoperineal resection for distal rectal cancer.
AB  - PURPOSE: To examine the complications, local effects, survival, and prognostic
      factors of preoperative high-dose radiation therapy in patients with advanced
      carcinomas of the distal rectum. METHODS: Forty-one patients with tethered or
      fixed rectal cancer located a median distance of 3.0 cm from the anal verge were
      treated with extracorporeal and endocavitary radiation therapy (70 Gy), followed
      2 weeks later by abdominoperineal resection (APR). RESULTS: This combined
      radiotherapy achieved acceptable results. Postoperative complications developed
      in 18 patients (43.9%), 10 (24.3%) of which involved perineal dehiscence. Two
      patients (4.8%) suffered more than grade 3 toxicity. Destructive changes were
      histologically confirmed in all specimens, and there were four (9.8%) sterile
      specimens. Recurrence developed in 11 patients and there were 6 cancer-related
      deaths. Among six cases of local recurrence, three were found just outside of the
      radiation field. The 5-year survival and disease-free survival rates were 82.9%
      and 71.8%, respectively. Multivariate analysis revealed that nodal involvement
      was the sole independent prognostic factor for survival. Sexual function was
      maintained in the most recent patients who underwent APR with autonomic nerve
      preserving surgery. CONCLUSION: Although the original aim of our treatment
      focused on curability, this combination therapy may be an option for selected
      patients, because of potential prevention of local recurrence, relatively low
      morbidity, and promising autonomic nerve function.

PMID- 15170548
TI  - Amyloid tumor in the anterior mediastinum: report of a case.
AB  - A 33-year-old woman being treated for rheumatoid arthritis was referred to our
      hospital for investigation of a mediastinal mass. A chest computed tomography
      scan showed an anterior mediastinal mass, 8.5 x 7.0 cm in size, with a cystic
      lesion and calcification. These findings were suggestive of either a noninvasive
      thymoma or a mature teratoma. Therefore, we performed tumor resection and
      thymectomy. Histologically, the tumor consisted of diffuse deposits of massive
      eosinophilic amorphous material. The tumor was stained red-orange by Congo red,
      and the staining disappeared following potassium permanganate digestion. Based on
      these findings, a diagnosis of reactive amyloidosis of the amyloid A-protein
      derived type was made. Amyloidosis in the mediastinum has rarely been described.

PMID- 15170549
TI  - Synovial sarcoma of the mediastinum: report of a case.
AB  - We report a case of synovial sarcoma of the mediastinum, a very rare tumor, in a
      50-year-old man hospitalized with anterior chest pain. Chest X-ray and computed
      tomography (CT) on admission showed a 10 x 8-cm mass in the right anterior
      mediastinal space, compressing the superior vena cava. A diagnosis of sarcoma was
      established by a CT-guided percutaneous needle biopsy. Systemic examination
      revealed no metastasis to the contralateral pleural cavity or other distant
      organs, and we resected the mediastinal sarcoma. Pathological and
      immunohistochemical analyses confirmed a diagnosis of monophasic synovial
      sarcoma. The patient is alive with recurrence 9 months after his operation, and
      is receiving chemotherapy with ifosfamide.

PMID- 15170550
TI  - Benefits of home parenteral nutrition before lung transplantation: report of a
      case.
AB  - A 54-year-old woman, who was severely malnourished and awaiting lung
      transplantation for chronic respiratory failure, was given nutritional support by
      home parenteral nutrition (HPN). The patient's emaciated state was further
      compromised by the fact that she had undergone a distal gastrectomy 4 years
      earlier. We decided that HPN was indicated because her oral intake was so poor
      and drinking enteral formula reduced her appetite. After 1 year of HPN, her body
      weight increased and her nutritional, anthropometric, and biochemical values were
      well maintained by the time of transplantation. Moreover, her progress after lung
      transplantation was remarkably good, indicating the effectiveness of nutritional
      support by HPN during the protracted waiting period.

PMID- 15170551
TI  - Successful endovascular stent-graft treatment for an aortoesophageal fistula
      caused by a descending thoracic aortic aneurysm: report of a case.
AB  - Conventional surgery for aortoesophageal fistula (AEF) is technically difficult,
      and is associated with high morbidity and mortality. We report a case of primary
      AEF caused by a descending thoracic aortic aneurysm, which was successfully
      treated with an endovascular stent-graft technique. The patient has been followed
      up for 3 years with no signs of infection.

PMID- 15170552
TI  - Diagnosis and treatment of a gastric hamartomatous inverted polyp: report of a
      case.
AB  - Gastric hamartomatous polyps are rare and difficult to diagnose. We report the
      case of a 43-year-old woman admitted to our hospital after an upper
      gastrointestinal series revealed a submucosal tumor. Upper gastrointestinal
      endoscopy showed a submucosal tumor (SMT), which was eroded with a depression on
      its surface, in the upper corpus. Endoscopic ultrasonography showed a
      heterogeneous tumor in the third layer. A laparoscopic wedge resection of the
      stomach allowed us to perform complete resection of the tumor, which measured 2.8
      cm in diameter. The pathological diagnosis was a gastric hamartomatous inverted
      polyp. The postoperative course was uneventful. Only 27 cases of gastric
      hamartomatous polyps have been reported in Japan. Hamartomatous inverted polyps
      without a stalk are classified as the "SMT type" because the tumor is inverted
      into the submucosal layer, whereas polyps with a stalk are classified as the
      "polyp type." All of the polyps in past reports were resected endoscopically;
      however, laparoscopic wedge resection may be indicated for SMT-type hamartomatous
      inverted polyps larger than 2.0 cm in diameter.

PMID- 15170554
TI  - Gastrointestinal metastases from malignant melanoma: report of a case.
AB  - Malignant melanoma metastases in the gastrointestinal tract (GIT) are found in
      more than 60% of autopsies on patients who have died with disseminated melanoma;
      however, the rate of GIT metastases detected clinically averages only 2%. This
      discrepancy seems to be attributed to the nonspecific symptoms and signs of GIT
      involvement, which include weakness, fatigue, bleeding, anemia, and abdominal
      pain. Sometimes a diagnosis is only made when bowel obstruction occurs. We report
      a case of long-term survival after surgery for multiple melanoma metastases in
      the gastrointestinal tract and review the relevant literature. Both our case
      report and the literature review demonstrate the benefits of surgery for patients
      with melanoma metastases in the GIT. We also stress the need for meticulous
      follow-up, detailed history-taking, and rapid evaluation of any vague and unclear
      abdominal signs and symptoms for patients with melanoma.

PMID- 15170553
TI  - Tuberculous gastric perforation: report of a case.
AB  - A 21-year-old woman presented with a 2-day history of acute abdominal pain.
      Contrast-enhanced computed tomography (CT) showed a perforation in the lesser
      curve of the stomach. The patient suffered a bout of hematemesis, following which
      an endoscopy showed a bleeding blood vessel at the edge of the perforation. We
      performed an emergency distal gastrectomy, including the ulcer site.
      Histopathological examination revealed tuberculous granulation tissue and acid
      fast bacilli in the ulcer. The patient was given antituberculosis therapy (ATT)
      postoperatively, and was well when last seen 1 year 5 months after surgery. We
      analyzed the clinical data of five cases of tuberculous gastric perforation
      (TGP), reported between 1948 and 2003, including our patient. The patients ranged
      in age from 21 to 45 years, with a mean age of 36.8 years (SD +/- 10.21), and a
      male to female ratio of 3 : 2. The diagnosis was confirmed by surgery or autopsy.
      Abdominal lymphadenopathy was present in all patients. Gastrectomy was performed
      in four patients, and two were given ATT. All four patients in the previous
      reports died of their disease.

PMID- 15170555
TI  - Retractile mesenteritis: report of a case.
AB  - Retractile mesenteritis is a rare idiopathic inflammatory process of the
      mesenteric adipose tissue. A 58-year-old woman who presented with acute abdominal
      pain and vomiting underwent laparotomy for a small bowel obstruction of unknown
      etiology. The laparotomy showed dilated small bowel loops and multiple tumor-like
      fibrous plaques in the mesentery. Histological examination revealed nonspecific
      chronic inflammatory processes of the mesentery. The computed tomography finding
      of increased density of the mesenteric fat, known as the "fat-ring sign," in a
      patient with small bowel obstruction and no surgical history would suggest this
      rare diagnosis.

PMID- 15170556
TI  - Melanotic schwannoma of the pancreas: report of a case.
AB  - We report a case of pancreatic melanotic schwannoma mimicking an epithelial
      cystic neoplasm of the pancreas. A 67-year-old Japanese woman underwent routine
      ultrasonography, which showed a large cystic mass in the head of the pancreas.
      Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI)
      showed an inhomogeneous, round cystic mass, which was encapsulated, in the head
      of the pancreas. We performed pyrolus-preserving pancreatoduodenectomy under the
      tentative diagnosis of a cystic neoplasm of the pancreas. The histopathologic
      diagnosis was benign melanotic schwannoma. The patient is now well after 43
      months of follow-up. We describe the CT and MRI findings in detail, and review
      the literature on previously reported cases of pancreatic schwannoma.

PMID- 15170557
TI  - Primary melanoma of the adrenal gland, a continuous dilemma: report of a case.
AB  - The adrenal gland can frequently be the site of metastatic deposits, including
      malignant melanocytic tumors; however, primary melanoma of the adrenal gland is
      exceptional. We reviewed 18 cases reported in the English literature to date, and
      here add another case which occurred in a 78-year-old man. The patient underwent
      right suprarenalectomy and the pathology report showed a malignant melanoma of
      the adrenal gland. Immunohistochemical staining revealed a positive antibody
      specific cytoplasmic reactivity to S-100 and HMB-45 proteins with a negative
      reaction for cytokeratin (AE1, AE3), synaptophysin, chromogranin and neuron
      specific enolase. There are diagnostic criteria for accepting an adrenal melanoma
      as primary; however, an autopsy is the final step to confirm this infrequent
      pathology.

PMID- 15170558
TI  - Diagnostic lobectomy for unilateral follicular nodules of the thyroid gland.
AB  - We describe our technique of diagnostic lobectomy (DL) and the rationale it is
      based on. We define DL as a minimally invasive procedure consisting of total
      lobectomy and isthmusectomy, with preservation of the omolateral recurrent
      laryngeal nerve and parathyroid glands, but without digital exploration of the
      contralateral lobe. The fact that re-entry into the previously explored field to
      complete thyroidectomy increases the risk of complications must be taken into
      consideration. The subjects were 63 consecutive patients who underwent surgery
      for unilobar follicular neoplasms of the thyroid gland between January 1997 and
      December 2002. There were 49 follicular adenomas and 14 carcinomas. In the 14
      patients with thyroid cancer, total thyroidectomy was performed within 2 weeks
      after the first operation in a sterile environment with normal anatomical
      cleavage plains, avoiding any risk of injury to the laryngeal nerves and
      parathyroid glands. It is concluded that DL is a safe and suitable surgical
      procedure for patients with follicular-structured lesions of the thyroid gland.

PMID- 15170559
TI  - Direct-vision retrosternal dissection using the Kent retractor for sternal re
      entry.
AB  - Repeat median sternotomy is still associated with high morbidity and mortality
      from catastrophic hemorrhage or myocardial injury. To overcome these problems, we
      devised a new technique of sternal re-entry using the Kent retractor set
      (Takasago Ika Kogyo, Tokyo, Japan), which increases the safety of retrosternal
      dissection and sternal redivision.

PMID- 15170560
TI  - Laparoscopic left-sided Nissen fundoplication in children.
AB  - It is sometimes difficult or inappropriate to adopt the standard surgical steps
      of adult laparoscopic procedures in pediatric patients because of the inevitably
      smaller anatomical structures and confined intra-abdominal working space. During
      laparoscopic Nissen fundoplication difficulties are usually encountered,
      especially when dissecting the diaphragmatic crura, creating the retroesophageal
      window, and repairing the crura. Thus, we devised a technique to accomplish these
      steps in pediatric patients. Both crural dissection and repair are approached
      from the left side of the esophagus and the port configuration for the
      laparoscope and other instruments is altered, providing better surgical exposure
      and easier handing of the instruments, even in very small patients. We describe
      this technique in detail and our results.

PMID- 15170561
TI  - Characterizing the interaction between the bogus yucca moth and yuccas: do bogus
      yucca moths impact yucca reproductive success?
AB  - Yucca moths are most well known for their obligate pollination mutualism with
      yuccas, where pollinator moths provide yuccas with pollen and, in exchange, the
      moth larvae feed on a subset of the developing yucca seeds. The pollinators,
      however, comprise only two of the three genera of yucca moths. Members of the
      third genus, Prodoxus, are the "bogus yucca moths" and are sister to the
      pollinator moths. Adult Prodoxus lack the specialized mouthparts used for
      pollination and the larvae feed on plant tissues other than seeds. Prodoxus
      larvae feed within the same plants as pollinator larvae and have the potential to
      influence yucca reproductive success directly by drawing resources away from
      flowers and fruit, or indirectly by modifying the costs of the mutualism with
      pollinators. We examined the interaction between the scape-feeding bogus yucca
      moth, Prodoxus decipiens, and one of its yucca hosts, Yucca filamentosa, by
      comparing female reproductive success of plants with and without moth larvae. We
      determined reproductive success by measuring a set of common reproductive traits
      such as flowering characteristics, seed set, and seed germination. In addition,
      we also quantified the percent total nitrogen in the seeds to determine whether
      the presence of larvae could potentially reduce seed quality. Flowering
      characteristics, seed set, and seed germination were not significantly different
      between plants with and without bogus yucca moth larvae. In contrast, the percent
      total nitrogen content of seeds was significantly lower in plants with P.
      decipiens larvae, and nitrogen content was negatively correlated with the number
      of larvae feeding within the inflorescence scape. Surveys of percent total
      nitrogen at three time periods during the flowering and fruiting of Y.
      filamentosa also showed that larval feeding decreased the amount of nitrogen in
      fruit tissue. Taken together, the results suggest that although P. decipiens
      influences nitrogen distribution in Y. filamentosa, this physiological effect
      does not appear to impact the female components of reproductive success.

PMID- 15170562
TI  - Projections and chemistry of Dogiel type II neurons in the mouse colon.
AB  - The physiological properties, shapes, projections and neurochemistries of Dogiel
      type II neurons have been thoroughly investigated in the guinea-pig intestine in
      which these neurons have been identified as intrinsic primary afferent neurons.
      Dogiel type II neurons in the myenteric ganglia of mice have similar
      physiological properties to those in guinea-pigs but whether other features of
      the neurons are similar is unknown. We have used intracellular dye-filling,
      retrograde tracing, immunohistochemistry and nerve lesions to determine salient
      features of Dogiel type II neurons of the mouse colon. Dye-filling showed that
      the neurons provide profuse terminal networks in the myenteric ganglia and also
      have axons that project towards the mucosa. Retrograde tracing and lesion studies
      showed that these axons provide direct innervation to the mucosa. High
      proportions of the neurons had immunoreactivity for calretinin, calbindin,
      choline acetyltransferase, the purine P2X2 receptor and calcitonin gene-related
      peptide (CGRP). CGRP was the most selective marker of the neurons. Following
      surgery to remove an area of myenteric plexus, the CGRP-immunoreactive nerve
      fibres in the mucosa degenerated. Thus, Dogiel type II neurons in mice have
      similar shapes and projections but some differences in chemistry from those in
      guinea-pigs. The close similarities between the two species in the shapes,
      projections and electrophysiology of these neurons suggest that they serve the
      same functions in both species.

PMID- 15170563
TI  - Effects of growth hormone on the ultrastructure of bovine preimplantation
      embryos.
AB  - Growth hormone (GH) has recently been shown to promote the development of
      preimplantation embryos. The aim of our study was therefore to analyze the
      effects of GH on the morphology and ultrastructure of the cells of bovine
      preimplantation embryos produced by in vitro fertilization (IVF). In order to
      determine the physiologically optimal morphology of blastocysts, ex vivo embryos
      obtained by uterine flushing were also included in the study. As shown by
      transmission electron microscopy, treatment with GH induced the elimination of
      glycogen storage in cells of the inner cell mass of 7-day-old embryos. GH also
      stimulated the exocytosis of lipid vesicles in the inner cell mass and
      trophectoderm cells of these embryos. Quantitative analysis of micrographs
      demonstrated a higher volume density of embryonic mitochondria in 7-day-old
      embryos cultured with GH than in control embryos. Treatment with GH regularly
      resulted in an improvement of the ultrastructural features of embryos produced in
      vitro, thus resembling the morphology of ex vivo embryos. Scanning electron
      microscopy studies demonstrated that GH altered the structure and the pore size
      of the zona pellucida of blastocysts. Our studies imply that GH can modulate
      carbohydrate, lipid, and energy metabolism and influence transportation processes
      in the early IVF embryo.

PMID- 15170564
TI  - The expression of functional human parathyroid hormone in a gene therapy model
      for osteoporosis.
AB  - The pro-peptide sequence of human parathyroid hormone (hPTH) is essential for the
      efficient translocation of the nascent polypeptide and the precise cleavage at
      residue +1 from the cleavage site. If residue +1 is not a serine, the bioactivity
      of hPTH decreases dramatically. In order to express the functional hPTH properly
      in a gene therapy model, we constructed three sets of eukaryotic expression
      vectors: one combining hPTH cDNA with its pre-sequence or its prepro-sequence;
      one combining hPTH cDNA with the insulin pre-sequence or with the insulin pre
      sequence and the hPTH pro-sequence; one combining pro-insulin cDNA with the hPTH
      pre-sequence or prepro-sequence. Radioimmunoassay and reverse
      transcription/polymerase chain reaction showed that transgenes were expressed in
      the animal model. The hPTH expressed by the vectors with the pro-sequence of PTH
      improved bone mechanical properties and bone mineral content, whereas the
      expressed insulin decreased blood glucose. Our results demonstrated that the pro
      sequence of hPTH was required for skeletal muscle cells to secrete functional
      hPTH into the circulation of our gene therapy model. However, the function of
      expressed insulin was not affected by the fusion of the hPTH pro-sequence. We
      concluded that pre-sequence, pro-sequence and mature hPTH acted as an integrated
      unit in skeletal muscle to guarantee the proper processing and release of
      functional hPTH into the circulation.

PMID- 15170567
TI  - A severe case of infant botulism caused by Clostridium botulinum type A with
      concomitant intestinal viral infections.

PMID- 15170566
TI  - Prevalence of Enterocytozoon bieneusi in post-weaned dairy calves in the eastern
      United States.
AB  - Fecal specimens were obtained from 3- to 8-month-old post-weaned dairy calves on
      farms in Vermont, New York, Pennsylvania, Maryland, Virginia, North Carolina, and
      Florida. After removal of fecal debris by sieving and density gradient
      centrifugation, 59 of 452 calves (13%) from 11 farms in six states were found
      positive for Enterocytozoon bieneusi by PCR and DNA sequence analysis. Based on
      gene sequence data this genotype of E. bieneusi found in post-weaned calves was
      100% identical to that found in pre-weaned calves in North America and differed
      by only two positions in 1,069 base pairs from specimens analyzed from humans.
      However, compared with previous reports, the prevalence of E. bieneusi was
      significantly higher in post-weaned than in pre-weaned calves from many of the
      same farms.

PMID- 15170568
TI  - Juvenile hormone acts at embryonic molts and induces the nymphal cuticle in the
      direct-developing cricket.
AB  - During embryogenesis of hemimetabolous insects, the sesquiterpenoid hormone,
      juvenile hormone (JH), appears late in embryogenesis coincident with formation of
      the first nymphal cuticle. We tested the role of embryonic JH by treating cricket
      embryos with JH III, or the JH-mimic (JHM) pyriproxifen, during early
      embryogenesis. We found two discrete windows of JH sensitivity. The first occurs
      during the formation of the first (E1) embryonic cuticle. Treatment with JHM
      prior to this molt produced small embryos that failed to complete the movements
      of katatrepsis. Embryos treated after the E1 molt but before the second embryonic
      (pronymphal) molt completed katatrepsis but then failed to complete dorsal
      closure and precociously formed nymphal, rather than pronymphal characters. This
      second sensitivity window was further assessed by treating embryos with low doses
      of JH III prior to the pronymphal molt. With low doses, mosaic cuticles were
      formed, bearing features of both the pronymphal and nymphal stages. The nymphal
      characters varied in their sensitivity to JH III, due at least in part to
      differences in the timing of their sensitivity windows. Unexpectedly, many of the
      JH III-treated embryos with mosaic and precocious nymphal cuticles made a second
      nymphal cuticle and successfully hatched. JH treatment also affected the growth
      of the embryos. By focusing on the developing limb, we found that the effect of
      JH upon growth was asymmetric, with distal segments more affected than proximal
      ones, but this was not reflected in misexpression of Distal-less or Bric-a-brac,
      which are involved in proximal-distal patterning of the limb.

PMID- 15170570
TI  - Glycogen reduction in non-exercising muscle depends on blood lactate
      concentration.
AB  - The purpose of this study was to determine for the first time by repeated non
      invasive 13C-NMR spectrometry whether blood lactate concentration affects
      glycogen reduction in non-exercising muscle during prolonged (6 h) physical
      exercise in healthy adult males. Such an effect would indirectly show that
      glycogenolysis independent of nervous activation occurs in non-exercising muscle.
      After an overnight fast, 12 subjects performed alternating one-leg cycle exercise
      and arm cranking exercise at an average work load of 106 (SD 26) W [63 (9)%
      maximum oxygen consumption for one-leg exercise] and 69 (13) W [61 (10)% maximum
      oxygen consumption for arm cranking exercise], respectively. During the 6-h
      exercise test, glycogen concentration of the non-exercising calf muscle decreased
      by 17 (7)% while the glycogen concentration in the exercising calf muscle
      decreased by 45 (8)%. In a resting control group (n=6), the glycogen
      concentration did not decrease significantly. The higher the exercise intensity
      and therefore blood lactate concentration, the smaller was the glycogen reduction
      in the non-exercising calf muscles. We conclude that during prolonged physical
      exercise glycogenolysis in non-exercising human muscles decreases as exercise
      intensity increase contrary to exercising muscles. This observation might be an
      indirect evidence for a non-exercise induced glycogenolysis in inactive muscles.

PMID- 15170569
TI  - The evolution of patterning of serially homologous appendages in insects.
AB  - Arthropod bodies are formed by a series of appendage-bearing segments, and
      appendages have diversified both along the body axis within species and between
      species. Understanding the developmental basis of this variation is essential for
      addressing questions about the evolutionary diversification of limbs. We examined
      the development of serially homologous appendages of two insect species, the
      beetle Tribolium castaneum and the grasshopper Schistocerca americana. Both
      species retain aspects of ancestral appendage morphology and development that
      have been lost in Drosophila, including branched mouthparts and direct
      development of appendages during embryogenesis. We characterized the expression
      of four genes important in proximodistal axis development of Drosophila
      appendages: the secreted signaling factors wingless and decapentaplegic, and the
      homeodomain transcription factors extradenticle and Distal-less. Our comparisons
      focus on two aspects of appendage morphology: differentiation of the main axis of
      serial homologues and the appearance of proximal branches (endites) in the
      mouthparts. Although Distal-less expression is similar in endites and palps of
      the mouthparts, the expression of other genes in the endites does not conform to
      their known roles in axial patterning, leading us to reject the hypothesis that
      branched insect mouthparts develop by reiteration of the limb patterning network.
      With the exception of decapentaplegic, patterning of the main appendage axis is
      generally more similar in direct homologues than in serial homologues.
      Interestingly, however, phylogenetic comparisons suggest that patterning of
      serial homologues was more similar in ancestral insects, and thus that the
      observed developmental differences did not cause the evolutionary divergence in
      morphology among serial homologues.

PMID- 15170572
TI  - Lung heat transfer.

PMID- 15170571
TI  - Does resistance exercise prevent body fluid changes after a 90-day bed rest?
AB  - Although various exercise regimens are commonly used as countermeasures to reduce
      the cardiovascular deconditioning induced by microgravity, the underlying
      mechanisms are not well understood. In this study we aimed to test whether lower
      limb resistance exercise with flywheel technology can prevent the fluid
      homeostasis alterations induced by 90-day head-down tilt bed-rest (HDT), and thus
      improve orthostatic tolerance. Total body water (TBW, measured by isotope
      dilution) and plasma volume (PV, calculated from the haemoglobin and the
      haematocrit) were measured in a control group (Co, n=9) and a countermeasure
      group (CM, n=9). Simultaneously, plasma atrial natriuretic peptide (ANP), renin
      (AR), and aldosterone (Aldo), as well as urinary anti-diuretic hormone (ADH),
      were measured. Orthostatic tolerance was evaluated with a 10 min +80 degrees tilt
      test the first day of recovery. After HDT, both groups showed a comparable
      decrease in orthostatic tolerance [8.2 (0.9) min, Co; 8.0 (0.7) min, CM], PV [
      4.7 (1.8)%, Co; -6.2 (2.5)%, CM, P<0.05] and TBW [-6.3 (5.4)%, Co; -3.7 (2.1)%,
      CM, P<0.05]. AR [97.4 (22.0)%, Co; 117.3 (26.4)%, CM] and Aldo [111.3 (58.4)%,
      Co; 100.6 (52.0)%, CM] increased significantly in both groups but the
      countermeasures produced no noticeable effects [data are expressed as mean (SE)].
      The drop in ANP was also similar in both groups [-42.0 (15.2)%, Co; -51.1 (27.7)%
      for the CM]. Surprisingly, urinary ADH declined similarly in both groups during
      the basal data control period [-25.3 (5.2)%, Co; -26.1 (9.6)%, CM) and was
      sustained at this level during the 90-day HDT. These results show that, under the
      conditions described, the flywheel exercise device failed to improve
      characteristic manifestations of cardiovascular deconditioning and suggest that
      more frequent and powerful exercise, associated with another device (e.g. LBNP)
      might be a better countermeasure.

PMID- 15170573
TI  - Decomposition of carrion in the marine environment in British Columbia, Canada.
AB  - Decomposition of carrion in the marine environment is not well understood. This
      research involved the decomposition of pig carcasses in Howe Sound in British
      Columbia. Freshly killed pigs were submerged at two depths, 7.6 m and 15.2 m. The
      carcasses were tethered so that they could float or sink, but not drift away.
      Observations were made from May until October. Decomposition was more greatly
      influenced by sediment type of the sea floor and whether the carcass remained
      floating, than by depth. Decomposition stages were modified in the marine
      environment from that seen on land, or in freshwater and were similar to those
      reported in human death investigations in the marine environment.

PMID- 15170575
TI  - Laryngeal solitary fibrous tumor treated with CO2 laser excision: case report.
AB  - The solitary fibrous tumor is an uncommon unilateral benign lesion that usually
      arises from the pleura. Recently, these tumors have been described in many other
      locations, such as the mediastinum, head and neck, orbit and urogenital system.
      To date, only two cases of solitary fibrous tumor arising from the larynx have
      been reported in the scientific literature. We describe a new case of laryngeal
      solitary fibrous tumor localized at the right false vocal fold. A 29-year-old man
      presented with a 6-month history of progressive hoarseness and foreign body
      sensation in the throat. A mass lesion was recognized in the right false vocal
      fold, and CT scan demonstrated a large, well-defined tumor without signs of
      infiltration. The tumor was removed by transoral CO(2) laser surgery. The
      definitive diagnosis was obtained by immunohistochemical analysis that showed
      vimentin and CD34-positive cells. The patient remains free of tumor after 15
      months of follow-up.

PMID- 15170574
TI  - Dose-dependent dual effect of melatonin on ototoxicity induced by amikacin in
      adult rats.
AB  - The aim of this animal study was to reveal the dose-dependent effects of
      melatonin on aminoglycoside ototoxicity by utilizing distortion product
      otoacoustic emissions (DPOAEs). Forty-four adult (aged 12 months) rats were
      divided into five groups. Rats of the control group (group C) were injected with
      vehicle, while the melatonin group (group M) received melatonin (4 mg/kg per
      day); there were four rats in each of these groups. The study groups consisted of
      12 rats per group, and they were treated as follows: 600 mg/kg per day amikacin
      (group A), amikacin plus a low dose (0.4 mg/kg per day) melatonin (group AML) and
      amikacin plus high dose (4 mg/kg per day) melatonin (group AMH) for 14 days.
      During the serial measurements on days 0, 5, 10 and 15, the DPOAE results of
      groups C,M and AML were not significantly changed. Amikacin ototoxicity findings
      for input/output (I/O) functions were detected on the 3rd measurement of the
      study in group A. High-dose melatonin clearly enhanced and accelerated amikacin
      induced ototoxicity. The DP-gram amplitudes and I/O amplitudes were reduced, and
      I/O thresholds were increased in group AMH. Group AMH was the group that was
      affected the most and earliest by amikacin. Our study results showed that while
      low-dose melatonin protected the inner ear from ototoxicity, high dose melatonin
      facilitated amikacin-induced ototoxicity, possibly via the vasodilatory effect,
      leading to an increased accumulation of amikacin in the inner ear. Probably, the
      protective effect of the melatonin at a dose of 0.4 mg/kg per day is related to
      its antioxidant properties. Apparently, the vasodilatory effect of melatonin
      seems to be more prominent than its antioxidant effect in high doses.

PMID- 15170576
TI  - An office procedure to detect vestibular loss in children with hearing
      impairment.
AB  - As coexisting vestibular and cochlear lesions are of etiological importance,
      evaluation of children with congenital or early acquired hearing impairment (HI)
      should include vestibular assessment. A rotation test requires specific equipment
      and allows only detection of bilateral vestibular impairment. An impulse or head
      thrust test allows assessment of one ear at a time, detects more pronounced
      caloric side differences and can be performed without any equipment. We report a
      consecutive series of children with profound sensorineural HI investigated at a
      tertiary hospital unit. Age at taking first steps without help, the results of
      temporal bone images (CT/MRT) and vestibular tests were collected retrospectively
      from patient files. The children were 12 to 90 months old at the time they
      attended both a rotation and an impulse test. All 14 children cooperated in the
      impulse test, and 12 completed the vestibular rotation test successfully. Three
      out of 14 children tested so far have been confirmed to have a bilaterally
      pathological vestibulo-ocular reflex confirmed both in the rotation test and the
      impulse test. Our results show that both the rotation test and the vestibular
      impulse test can be successfully performed on small children at a regular
      outpatient appointment.

PMID- 15170577
TI  - Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor
      neuron disease: a quantitative immunocytochemical study.
AB  - Ubiquitin-positive tau-negative inclusions were initially described in the rare
      form of frontotemporal dementia (FTD) associated with motor neuron disease.
      However, recent studies have indicated that these inclusions are also present in
      typical FTD, which is usually characterized by nonspecific histological changes.
      To examine the contribution of these inclusions to neuronal loss and to explore
      their relationship with disease duration, we performed a quantitative
      immunocytochemical analysis of 38 typical FTD cases. Relationships between neuron
      and ubiquitin inclusion densities as well as between duration of illness and
      neuropathological parameters was studied using linear regression in both
      univariate and multivariate models. Ubiquitin-positive tau-negative
      intracytoplasmic inclusions were present in 65.8% of cases in the dentate gyrus,
      57.9% in temporal cortex and 31.6% in frontal cortex. The highest densities of
      ubiquitin-positive inclusions were consistently observed in the dentate gyrus,
      followed by the temporal and frontal cortex. There was no statistically
      significant relationship between neuron and ubiquitin-positive inclusion
      densities in any of the areas studied. In contrast, ubiquitin-positive inclusion
      densities in the dentate gyrus were negatively related to the duration of
      illness. Our data suggest that the development of ubiquitin-related pathology is
      the rule and not the exception in typical FTD, yet is not causally related to
      neuronal loss. They also reveal that the development of ubiquitin-positive
      inclusion densities in the dentate gyrus may be associated with a more aggressive
      form of the disease.

PMID- 15170579
TI  - [Health care ethics committees in German university clinics. A survey of all
      medical directors and directors of nursing].
AB  - OBJECTIVE: Health Care Ethics Committees (HEC) are new ways of implementing
      clinical ethics in hospitals and nursing homes. In the US all health care
      institutions must provide some structure to handle ethical conflicts in everyday
      patients' care. However, in Germany only a minority of hospitals, often members
      of the Protestant or Catholic Hospital Associations, have founded HEC. No studies
      exist in regard to the situation at German university hospitals. METHODS: In
      November 2002 we posted a questionnaire with 13 items to all medical directors
      (M) and directors of nursing (N) of the 36 German university hospitals. RESULTS:
      The response rate was 82 %. Limitation of treatment, informed consent and the
      conflict between beneficience and autonomy are the most relevant ethical issues
      in everyday practice. N estimated the need for additional support of their staff
      in ethical issues higher than M. Improvement of interdisciplinary teamwork,
      further education in ethics and ethical guidelines have been identified in order
      to improve ethical professional performance. However, N mentioned the lack of
      time and the low priority of ethics more often than M as problems in implementing
      theses measures. Five German university hospitals are planning to establish a HEC
      and two hospitals want to employ a clinical ethicist. CONCLUSION: Our data show a
      high need for information about HEC in German university hospitals. The tasks,
      working methods and chances for further development of HEC are neither known nor
      used in the majority of German university hospitals.

PMID- 15170578
TI  - alpha-Internexin aggregates are abundant in neuronal intermediate filament
      inclusion disease (NIFID) but rare in other neurodegenerative diseases.
AB  - Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF)
      subunits, NF-L, NF-M, and NF-H have recently been identified as the pathological
      hallmarks of neuronal intermediate filament (IF) inclusion disease (NIFID), a
      novel neurological disease of early onset with a variable clinical phenotype
      including frontotemporal dementia, pyramidal and extrapyramidal signs. alpha
      Internexin, a class IV IF protein, a major component of inclusions in NIFID, has
      not previously been identified as a component of the pathological protein
      aggregates of any other neurodegenerative disease. Therefore, to determine the
      specificity of this protein, alpha-internexin immunohistochemistry was undertaken
      on cases of NIFID, non-tau frontotemporal dementias, motor neuron disease, alpha
      synucleinopathies, tauopathies, and normal aged control brains. Our results
      indicate that class IV IF proteins are present within the pleomorphic inclusions
      of all cases of NIFID. Small subsets of abnormal neuronal inclusions in
      Alzheimer's disease, Lewy body diseases, and motor neuron disease also contain
      epitopes of alpha-internexin. Thus, alpha-internexin is a major component of the
      neuronal inclusions in NIFID and a relatively minor component of inclusions in
      other neurodegenerative diseases. The discovery of alpha-internexin in neuronal
      cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and
      other neurological diseases with pathological filamentous neuronal inclusions.

PMID- 15170580
TI  - [Unexpected cause of a tarsal destruction in a diabetic patient].
AB  - HISTORY: A 56-year-old male patient has suffered from increasing pain in the left
      foot which limited the ability of walking since 18 months. There was a soft and
      painful swelling below the left inner ankle. In addition the patient reported
      back pain, but no neurological symptoms. Insulin dependent diabetes type II was
      known for 20 years, and a diabetic foot syndrome was suspected. 6 months prior
      the patient consulted his physician because of repeated acute bronchitis with
      expectoration and no improvement following antibiotic therapy. INVESTIGATIONS:
      Osteolytic destruction of the left middle foot and the tarsal with soft tissue
      infiltration according to MR, a spondylodiscitis of the lumbar vertebra I and II
      (MR) and mixed interstitial/alveolar infiltrates throughout the lung with a
      predominance in both upper lobes were found. The microbiological examination of
      sputum and biopsy of inflamed soft tissue of the left ankle revealed infection
      with mycobacterium tuberculosis. DIAGNOSIS: Open lung tuberculosis with
      concomitant bone tuberculosis and tuberculous arthritis of the left middle foot
      and spondylodiscitis. THERAPY AND CLINICAL COURSE: The antibiotic therapy
      consisted of a combination of five antibiotic drugs for 2 weeks and of a four
      drug combination for further 3.5 months. After that there will be a consolidation
      therapy with a two drug regime for 6 months. An orthopaedist is also involved.
      Surgical procedures with respect to the left foot will not be considered as long
      as the antibiotic therapy has not been finished. CONCLUSION: A combination of
      symptoms resulting from inflammatory bone processes and pulmonary symptoms is
      always suspicious for a hematogenic dissemination of a pulmonary tuberculosis.

PMID- 15170581
TI  - [Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations].
AB  - HISTORY AND ADMISSION FINDINGS: A 49-years-old female with a history of multiple
      sclerosis and on medication with azathioprine over 5 years amounting to a
      cumulative dosage of 45 g presented with fatigue and sinus tachycardia.
      INVESTIGATIONS: Haematological analysis revealed a pancytopenia with a sustained
      normochromic anemia (hemoglobin 6,2 g/dl), a mild leukopenia (leucocytes 3500/
      microl) and thrombocytopenia (platelets 22000/ microl) requiring platelet
      substitution. Bone marrow aspirate revealed a dysplasia of all three lineages
      with reduced thrombopoiesis and ineffective erythropoiesis. Cytogenetic analysis
      detected a complex aberrant clone including loss of the critically deleted
      regions in 5q31 and 7q31, as well as structural changes of 12p. The diagnosis was
      refractory cytopenia with multilineage dysplasia according to the WHO
      classification of myelodysplastic syndromes. TREATMENT AND COURSE: While
      allogeneic sibling transplantation was planned the patient developed spontaneous
      recurrent subdural haematoma and died due to persistent bleeding refractory to
      platelet substitution. CONCLUSION: Treatment with azathioprine may - depending on
      its cumulative dosage - lead to pancytopenia and subsequent development of
      myelodysplasia or secondary leukaemia, respectively. Complex genetic alterations
      involving chromosome 7 are characteristic. Long-lasting treatment with
      azathioprine needs critical assessment.

PMID- 15170582
TI  - [Preoperative cardiovascular risk evaluation--case report].

PMID- 15170583
TI  - [Preoperative cardiovascular risk evaluation--diagnosis].

PMID- 15170584
TI  - [Preoperative cardiovascular risk evaluation--therapy].

PMID- 15170588
TI  - [Prospective study for the comparison of conventional and transnasal
      esophagogastroduodenoscopy in routine diagnosis].

PMID- 15170587
TI  - [Vascular progenitor cells and atherogenesis. Regression and regeneration using
      bone marrow?].

PMID- 15170590
TI  - Cyclooxygenase and 5-lipoxygenase pathways in the vessel wall: role in
      atherosclerosis.
AB  - Prostaglandins (PGs), thromboxanes (Txs), and leukotrienes (LTs) play a relevant
      role in cardiovascular physiology and pathophysiology. Recent reports concerning
      cardiovascular risk associated with cyclooxygenase-2 selective inhibitors have
      prompted questions about the "protective" or "deleterious" role of each COX
      isoform in cardiovascular disease, and the cloning and expression of inducible
      PGE-synthase (PGES) open the possibility that PGES could be a new therapeutical
      target in this context. Predominance of constricting or relaxing prostanoids
      depends not only on COX activity but also to downstream enzymes such as PGI
      synthase (PGIS) and PGES. In the vessel wall, PGIS and PGES seem to be major
      downstream enzymes in the endothelium and smooth muscle, respectively. Like COX,
      activity of these enzymes can also be regulated by several factors, which include
      nitrogen oxides, cytokines, and lipid peroxides. LTs are important inflammatory
      mediators also involved in the pathophysiology of cardiovascular disease, which
      are targets for pharmacological intervention. Unlike COX pathway, the
      biosynthesis of chemotactic and vaso-constrictor LTs in the vasculature strongly
      depends on leukocyte recruitment and activation, and on cell-cell interaction
      between leukocytes and vascular cells in the inflamed areas. The present review
      emphasizes the role of vascular-derived prostanoids and LTs on atherosclerosis.

PMID- 15170589
TI  - [The development of a toxic megacolon due to amanita mushroom poisoning].

PMID- 15170591
TI  - Synthetic peroxides as antimalarials.
AB  - The discovery of artemisinin in 1971 initiated a new era in antimalarial
      chemotherapy. Although the clinically useful semisynthetic artemisinin
      derivatives are rapid acting and potent antimalarial drugs, they have short half
      lives and must be administered over a period of 5-7 days, leading to
      noncompliance and recrudescence. With this in view, many synthetic antimalarial
      peroxides have been prepared. Yet, identification of orally active synthetic
      peroxide drug development candidates that are easily synthesized, inexpensive,
      and with good biopharmaceutical properties has been surprisingly difficult. In
      this review, we document the pitfalls and progress made in this endeavor. For
      each of 15 synthetic peroxide structural classes, we note highlights of the
      synthetic routes, product stereochemistry, and origin of the peroxide O atoms.
      Both in vitro and in vivo antimalarial data are then discussed and any SAR noted.
      Available data indicates that several synthetic 1,2,4-trioxanes are only
      marginally less effective than the semisynthetic artemisinins. Within a given
      peroxide chemical family, the more lipophilic members are more potent and possess
      better oral antimalarial activity in animal models than their more polar
      counterparts. This poses a challenge to identify peroxide structures with
      suitable "drug-like" physicochemical properties. Nonetheless, substantial
      progress has been made in the identification of a new generation of synthetic
      antimalarial peroxides.

PMID- 15170592
TI  - Selective human enterovirus and rhinovirus inhibitors: An overview of capsid
      binding and protease-inhibiting molecules.
AB  - The absence of effective vaccines for most viral infections highlights an urgent
      necessity for the design and development of effective antiviral drugs. Due to the
      advancement in virology since the late 1980s, several key events in the viral
      life cycle have been well delineated and a number of molecular targets have been
      validated, culminating in the emergence of many new antiviral drugs in recent
      years. Inhibitors against enteroviruses and rhinoviruses, responsible for about
      half of the human common colds, are currently under active investigation. Agents
      targeted at either viral protein 1 (VP1), a relatively conserved capsid structure
      mediating viral adsorption/uncoating process, or 3C protease, which is highly
      conserved among different serotypes and essential for viral replication, are of
      great potential to become antipicornavirus drugs.

PMID- 15170593
TI  - DNA minor groove binders as potential antitumor and antimicrobial agents.
AB  - DNA minor groove binders constitute an important class of derivatives in
      anticancer therapy. Some of these compounds form noncovalent complexes with DNA
      (e.g., distamycin A, Hoechst 33258, and pentamidine) while others DNA-binding
      compounds (such as CC-1065) cause cleavages in the DNA backbone. In this article,
      we have reviewed the minor groove binders currently in preclinical evaluation in
      the last years. Diarylamidines such as DAPI, berenil, and pentamidine; bis
      benzimidazoles such as Hoechst 33258; ecteinascidins, pyrrololo [2,1-c]-[1,4]
      benzodiazepines (PBDs), CC-1065, and distamycins are the classes discussed in
      this review article. A special section has been dedicated to hybrid molecules
      resulted by the combination of two minor groove binders, especially for
      derivatives of naturally occurring antitumor agents, such as anthramycin or the
      alkylating unit of the antibiotic CC-1065, and distamycin frames.

PMID- 15170594
TI  - Steroid sulfatase inhibitors.
AB  - Steroid sulfatase (STS) regulates the local production of estrogens and androgens
      from systemic precursors in several tissues. The enzyme catalyzes the hydrolysis
      of the sulfate esters of 3-hydroxy steroids, which are inactive transport or
      precursor forms of the active 3-hydroxy steroids. STS inhibitors are expected to
      block the local production and, consequently, to reduce the local levels of the
      hormones. Therefore, they are considered as potential new therapeutic agents for
      the treatment of estrogen- and androgen-dependent disorders. Indications range
      from cancers of the breast, endometrium and prostate to androgenetic alopecia and
      acne. In this review, we give a comprehensive summary of the current knowledge
      and problems in the field of medicinal chemistry of STS inhibitors. The various
      types of inhibitors are presented and their structure-activity relationships are
      discussed. In addition to potent arylsulfamate-based, irreversible inhibitors,
      novel types of reversible inhibitors were recently discovered. The recent
      publication of the X-ray structure of STS will further boost research activities
      on this attractive target.

PMID- 15170595
TI  - Cytomics--new technologies: towards a human cytome project.
AB  - BACKGROUND: Molecular cell systems research (cytomics) aims at the understanding
      of the molecular architecture and functionality of cell systems (cytomes) by
      single-cell analysis in combination with exhaustive bioinformatic knowledge
      extraction. In this way, loss of information as a consequence of molecular
      averaging by cell or tissue homogenisation is avoided. PROGRESS: The cytomics
      concept has been significantly advanced by a multitude of current developments.
      Amongst them are confocal and laser scanning microscopy, multiphoton fluorescence
      excitation, spectral imaging, fluorescence resonance energy transfer (FRET), fast
      imaging in flow, optical stretching in flow, and miniaturised flow and image
      cytometry within laboratories on a chip or laser microdissection, as well as the
      use of bead arrays. In addition, biomolecular analysis techniques like tyramide
      signal amplification, single-cell polymerase chain reaction (PCR), and the
      labelling of biomolecules by quantum dots, magnetic nanobeads, or aptamers open
      new horizons of sensitivity and molecular specificity at the single-cell level.
      Data sieving or data mining of the vast amounts of collected multiparameter data
      for exhaustive multilevel bioinformatic knowledge extraction avoids the
      inadvertent loss of information from unknown molecular relations being
      inaccessible to an a priori hypothesis. CHALLENGE: It seems important to address
      the challenge of a human cytome project using hypothesis-driven molecular
      information collection from disease associated cell systems, supplemented by
      systematic and exhaustive knowledge extraction. This will allow the description
      of the molecular setup of normal and abnormal cell systems within a relational
      knowledge system, permitting the standardised discrimination of abnormal cell
      states in disease. As one of the consequences, individualised predictions of
      further disease course in patients (predictive medicine by cytomics) by
      characteristic discriminatory data patterns will permit individualised therapies,
      identification of new pharmaceutical targets, and establishment of a standardised
      framework of relevant molecular alterations in disease. This special issue of
      Cytometry, on new technologies in cytomics, focuses on prominent examples of this
      presently fast-moving scientific field, and represents one of the preconditions
      for the formulation of a human cytome project.

PMID- 15170596
TI  - Application of spectral imaging microscopy in cytomics and fluorescence resonance
      energy transfer (FRET) analysis.
AB  - BACKGROUND: Specific signal detection has been a fundamental issue in
      fluorescence microscopy. In the context of tissue samples, this problem has been
      even more pronounced, with respect to spectral overlap and autofluorescence.
      METHODS: Recent improvements in confocal laser scanning microscopy combine
      sophisticated hardware to obtain fluorescence emission spectra on a single-pixel
      basis and a mathematical procedure called "linear unmixing" of fluorescence
      signals. By improving both the specificity of fluorescence acquisition and the
      number of simultaneously detectable fluorochromes, this technique of spectral
      imaging (SI) allows complex interrelations in cells and tissues to be addressed.
      RESULTS: In a comparative approach, SI microscopy on a quantitative basis was
      compared to conventional bandpass (BP) filter detection, demonstrating
      substantial superiority of SI with respect to detection accuracy and dye
      combination. An eight-color immunofluorescence protocol for tissue sections was
      successfully established. Moreover, advanced use of SI in fluorescence resonance
      energy transfer (FRET) applications using enhanced green fluorescence protein
      (EGFP) and enhanced yellow fluorescence protein (EYFP) in a confocal set up could
      be demonstrated. CONCLUSIONS: This novel technology will help to perform complex
      multiparameter investigations at the cellular level by increasing the detection
      specificity and permitting simultaneous use of more fluorochromes than with
      classical techniques based on emission filters. Moreover, SI significantly
      extends the possibilities for specialized microscopy applications, such as the
      visualization of macromolecular interactions or conformational changes, by
      detecting FRET.

PMID- 15170597
TI  - Microscopy-based multicolor tissue cytometry at the single-cell level.
AB  - Cytomics is a novel perspective from which to look at life. As with genomics and
      proteomics before, this discipline requires novel and innovative techniques and
      technologies to focus on its substrate of research--the cytome. With cytomics
      being the discipline that analyzes cellular systems and their interdependencies,
      advanced microscopy represents a key technology in cytomics research. Yet,
      conventional microscopy-based investigations, i.e., "look and conclude" analyses,
      do not meet the major cytomics criteria of 1) relating multiple parameters to
      each other, 2) within large populations of cells, 3) on a single-cell basis, and
      4) in a quantitative and observer-independent manner. However, emerging
      improvements in the fields of fluorophore technology, sensitive fluorescence
      detection devices, and sophisticated image analysis procedures, are important and
      necessary steps into the cytomics era. Tissue represents an important class of
      cytomes, hence tissue cytometry--on the single cell level--can be expected to
      become an important cytomics technology. In this report, the techniques and
      technologies of microscopy-based multicolor tissue cytometry (MMTC) are outlined
      and applications are discussed, including the phenotypic characterization of
      tissue infiltrating leukocytes, in situ quantification of proliferation markers
      and tumor suppressors, and in situ quantification of apoptosis.

PMID- 15170598
TI  - Getting the right cells to the array: Gene expression microarray analysis of cell
      mixtures and sorted cells.
AB  - BACKGROUND: Most biological samples are cell mixtures. Some basic questions are
      still unanswered about analyzing these heterogeneous samples using gene
      expression microarray technology (MAT). How meaningful is a cell mixture's
      overall gene expression profile (GEP)? Is it necessary to purify the cells of
      interest before microarray analysis, and how much purity is needed? How much does
      the purification itself distort the GEP, and how well can the GEP of a small cell
      subset be recovered? METHODS: Model cell mixtures with different cell ratios were
      analyzed by both spotted and Affymetrix MAT. GEP distortion during cell
      purification and GEPs of purified cells were studied. CD34+ cord blood cells were
      purified and analyzed by MAT. RESULTS: GEPs for mixed cell populations were found
      to mirror the cell ratios in the mixture. Over 75% pure samples were
      indistinguishable from pure cells by their overall GEP. Cell purification
      preserved the GEP. The GEPs of small cell subsets could be accurately recovered
      by cell sorting both from model cell mixtures and from cord blood. CONCLUSIONS:
      Purification of small cell subsets from a mixture prior to MAT is necessary for
      meaningful results. Even completely hidden GEPs of small cell subpopulations can
      be recovered by cell sorting.

PMID- 15170599
TI  - Deformability-based flow cytometry.
AB  - BACKGROUND: Elasticity of cells is determined by their cytoskeleton. Changes in
      cellular function are reflected in the amount of cytoskeletal proteins and their
      associated networks. Drastic examples are diseases such as cancer, in which the
      altered cytoskeleton is even diagnostic. This connection between cellular
      function and cytoskeletal mechanical properties suggests using the deformability
      of cells as a novel inherent cell marker. METHODS: The optical stretcher is a new
      laser tool capable of measuring cellular deformability. A unique feature of this
      deformation technique is its potential for high throughput, with the
      incorporation of a microfluidic delivery of cells. RESULTS: Rudimentary
      implementation of the microfluidic optical stretcher has been used to measure
      optical deformability of several normal and cancerous cell types. A drastic
      difference has been seen between the response of red blood cells and
      polymorphonuclear cells for a given optically induced stress. MCF-10, MCF-7, and
      modMCF-7 cells were also measured, showing that while cancer cells stretched
      significantly more (five times) than normal cells, optical deformability could
      even be used to distinguish metastatic cancer cells from nonmetastatic cancer
      cells. This trimodal distribution was apparent after measuring a mere 83 cells,
      which shows optical deformability to be a highly regulated cell marker.
      CONCLUSIONS: Preliminary work suggests a deformability-based cell sorter similar
      to current fluorescence-based flow cytometry without the need for specific
      labeling. This could be used for the diagnosis of all diseases, and the
      investigation of all cellular processes, that affect the cytoskeleton.

PMID- 15170600
TI  - Quantitative histology by multicolor slide-based cytometry.
AB  - BACKGROUND: In lymphatic organs, the quantitative analysis of the spatial
      distribution of leukocytes by tissue cytometry would give relevant information
      about alterations during diseases (leukemia, HIV, AIDS) and their therapeutic
      regimen, as well as in experimental settings. METHODS: We have developed a
      semiautomated analysis method for laser scanning cytometry (LSC) termed "multiple
      thresholding," which is suitable for archived or fresh biopsy material of human
      lymph nodes and tonsils. Sections are stained with PI for nuclear DNA and up to
      four antigens using direct or indirect immunofluorescence staining. Measurement
      is triggered on DNA-fluorescence (argon laser, Ar) or on specific cell labeling.
      Due to the heterogeneity of cell density, measurements are performed repeatedly
      at different threshold levels (low threshold: regions of low cellular density,
      germinal center; high threshold: dense regions, mantle zone). Data are acquired
      by single- (Ar) or dual-laser excitation (Ar-HeNe) in order to analyze single-
      (FITC) up to four-color (FITC/PE/PECy5/APC) stained specimen. RESULTS: Percentage
      and cellular density of cell-subsets is quantified in different microanatomical
      regions of the specimen. These data were highly correlated with manual scoring of
      identical specimens (r(2) = 0.96, P < 0.0001). With LSC, semiautomated operator
      independent immunophenotyping in tissue sections of lymphatic organs with up to
      three antibodies simultaneously is possible. CONCLUSIONS: We expect this tissue
      cytometric approach to yield new insight into processes during diseases and help
      to quantify the success of therapeutic interventions.

PMID- 15170602
TI  - Data pattern analysis for the individualised pretherapeutic identification of
      high-risk diffuse large B-cell lymphoma (DLBCL) patients by cytomics.
AB  - BACKGROUND: Clinical outcome predictions in phase III studies are mostly derived
      for patient groups, but not for individual patients, although individualised
      predictions are an ultimate goal to permit a personalised fine tuning of therapy.
      This may permit earlier application of target therapies, minimise general damage
      to the organism, and result in improved complete remission rates in malignant
      diseases. METHODS: In this study, Lymphochip cDNA microarray gene expression
      results of DLBCL patients, from a published prospective meta-analysis study on
      the prediction of group prognosis, were analysed for individualised predictions
      using a nonstatistical data pattern classification approach. The training set was
      comprised of the same 160 DLBCL patients as in the prognosis study, with the
      validation set of 80 patients remaining unknown to the learning process. This
      permits the assessment of prospective classifier performance towards unknown
      patients. RESULTS: Pretherapeutic predictions for the training and validation set
      patients were correct in 98.1% and 78.3% of the cases for nonsurvival and in
      67.3% and 45.3% for survival. The discriminatory data pattern consisted of 14
      known and 10 unknown gene products. CONCLUSIONS: The better than 95% correct
      pretherapeutic prediction for about one-half of the ultimately nonsurviving high
      risk patients of the training set is promising for clinical considerations about
      individualised therapy in such cases. Reliable individualised survival
      predictions are not possible with the information content of the present dataset.
      It seems necessary to investigate additional gene products, since survival may
      significantly depend on non-lymphocyte-associated genes that escape to the
      lymphocyte-oriented Lymphochip gene activation analysis.

PMID- 15170601
TI  - RNA and DNA aptamers in cytomics analysis.
AB  - BACKGROUND: The systematic evolution of ligands by exponential enrichment (SELEX)
      technique is a combinatorial library approach in which DNA or RNA molecules
      (aptamers) are selected by their ability to bind their protein targets with high
      affinity and specificity, comparable to that of monoclonal antibodies. In
      contrast to antibodies conventionally selected in animals, aptamers are generated
      by an in vitro selection process, and can be directed against almost every
      target, including antigens like toxins or nonimmunogenic targets, against which
      conventional antibodies cannot be raised. METHODS: Aptamers are ideal candidates
      for cytomics, as they can be attached to fluorescent reporters or nanoparticles
      in order to study biological function by fluorescence microscopy, by flow
      cytometry, or to quantify the concentration of their target in biological fluids
      or cells using ELISA, RIA, and Western blot assays. RESULTS: We demonstrate the
      in vitro selection of anti-kinin B1 receptor aptamers that could be used to
      determine B1 receptor expression during inflammation processes. These aptamers
      specifically recognize their target in a Northern-Western blot assay, and bind to
      their target protein whenever they are exposed in the membrane. CONCLUSIONS:
      Currently, aptamers are linked to fluorescent reporters. We discuss here the
      present status and future directions concerning the use of the SELEX technique in
      cytomics.

PMID- 15170603
TI  - Distinguishing modes of cell death using the ImageStream multispectral imaging
      flow cytometer.
AB  - BACKGROUND: Here we demonstrate the ability of the ImageStream 100 Multispectral
      Imaging Cytometer to discriminate between live, necrotic, and early and late
      apoptotic cells, using unique combinations of photometric and morphometric
      features. METHODS: Live, necrotic, and early and late apoptotic cells were
      prepared and analyzed by immunofluorescence microscopy, conventional flow
      cytometry, and imaging flow cytometry, both as single populations and as a
      heterogeneous mixture of cells. RESULTS: Live (annexin V(-), 7-AAD(-)) and early
      apoptotic (annexin V(+), 7-AAD(-)) cells were readily identifiable using either
      conventional or ImageStream based flow cytometric methods. However, inspection of
      multispectral images of cells demonstrated that the annexin V(+), 7-AAD(+)
      population contained both necrotic and late-stage apoptotic cells. Although these
      cells could not be distinguished using conventional flow cytometric techniques,
      they were separable using unique combinations of photometric and morphometric
      measures available using ImageStream technologies. CONCLUSIONS: Using
      multispectral imagery, morphologically distinct cell populations can be
      distinguished using features not available with conventional flow cytometers. In
      particular, the ability to couple morphometric with photometric measures makes it
      possible to distinguish live cells from cells in the early phases of apoptosis,
      as well as late apoptotic cells from necrotic cells.

PMID- 15170604
TI  - Single-cell analysis of yeast, mammalian cells, and fungal spores with a
      microfluidic pressure-driven chip-based system.
AB  - BACKGROUND: Cytomics aims at understanding the function of cellular systems by
      analysis of single cells. Recently, there has been a growing interest in single
      cell measurements being performed in microfluidic systems. These systems promise
      to integrate staining, measurement, and analysis in a single system. One
      important aspect is the limitation of allowable cell sizes due to microfluidic
      channel dimensions. Here we want to demonstrate the broad applicability of
      microfluidic chip technology for the analysis of many different cell types.
      METHODS: We have developed a microfluidic chip and measurement system that allows
      flow cytometric analysis of fluorescently stained cells from different organisms.
      In this setup, the cells are moved by pressure-driven flow inside a network of
      microfluidic channels and are analyzed individually by fluorescence detection.
      RESULTS: We have successfully applied the system to develop a methodology to
      detect viable and dead cells in yeast cell populations. Also, we have measured
      short interfering RNA (siRNA) mediated silencing of protein expression in
      mammalian cells. In addition, we have characterized the infection state of
      Magnaportae grisea fungal spores. CONCLUSIONS: Results obtained with the
      microfluidic system demonstrate a broad applicability of microfluidic flow
      cytometry to measurement of various cell types.

PMID- 15170605
TI  - Microgenomics: Identification of new expression profiles via small and single
      cell sample analyses.
AB  - BACKGROUND: Since the sequencing of the human genome has been finished,
      microgenomics has been booming, employing highly sophisticated, high-throughput
      platforms. But these mainly chip-based methods can only generate biologically
      relevant data if the samples investigated consist of homogeneous cell
      populations, in which no unwanted cells of different specificity and/or
      developmental stage obscure the results. METHODS: Different sampling methods have
      been routinely applied to overcome the problem presented by heterogeneous
      samples, e.g., global surveys, cell cultures, and microdissection. Various
      methods of laser-assisted microdissection, employing either positive or negative
      selection of tissue areas or even single cells, are available. RESULTS: These
      laser-assisted microdissection methods allow for fast and precise procurement of
      extremely small samples. Through subsequent application of recently developed
      methods of linear mRNA amplification in a pool of isolated total RNA, it has now
      become possible to perform complex high-throughput RNA expression profiling by
      microdissecting and processing even single-cell samples. CONCLUSIONS: Studies
      using the tools and methods of microgenomics have shed light on how those new
      approaches will eventually aid in the development of a new generation of
      diagnostics, e.g., leading to new patient-specific drugs tailored to the
      requirements assessed by assaying only a few biopsy cells.

PMID- 15170607
TI  - From canine to man: on antibodies, macrophages, and dendritic cells in
      inflammatory myopathies.

PMID- 15170608
TI  - Opportunities afforded by the study of unmyelinated nerves in skin and other
      organs.
AB  - Neurological practice is mainly focused on signs and symptoms of disorders that
      involve functions governed by myelinated nerves. Functions controlled by
      unmyelinated nerve fibers have necessarily remained in the background because of
      the inability to consistently stain, image, or construct clinically applicable
      neurophysiological tests of these nerves. The situation has changed with the
      introduction of immunohistochemical methods and confocal microscopy into clinical
      medicine, as these provide clear images of thin unmyelinated nerves in most
      organs. One obvious sign of change is the increasing number of reports from
      several laboratories of the pathological alterations of cutaneous nerves in skin
      biopsies from patients with a variety of clinical conditions. This study reviews
      recent methods to stain and image unmyelinated nerves as well as the use of these
      methods for diagnosing peripheral neuropathy, for experimental studies of
      denervation and reinnervation in human subjects, and for demonstrating the vast
      array of unmyelinated nerves in internal organs. The new ability to examine the
      great variety of nerves in different organs opens opportunities and creates
      challenges and responsibilities for neurologists and neuroscientists.

PMID- 15170609
TI  - Whiplash: pathophysiology, diagnosis, treatment, and prognosis.
AB  - We have reviewed the literature relevant to pathophysiology, diagnosis,
      treatment, and prognosis of whiplash-associated disorder (WAD) since 1995 and
      provided a brief summary of literature pertaining to forces action on the head
      and neck during a motor vehicle accident. The scope of the current review is
      confined to the Quebec guidelines for WAD grades 1-3 but excludes grade 4 (neck
      complaints and fracture or dislocation). After excluding papers without
      scientific data and single case reports or case series with fewer than 20
      patients, articles were reviewed for methodological quality. The diagnosis
      remains clinical. No imaging, physiological, or psychological study provides
      specific diagnostic criteria. In the acute period up to 2 weeks, soft collars or
      rest and work-leave do not shorten the duration of neck pain. Sick leave is
      reduced by high-dose methylprednisolone given within 8 h of injury, but
      confirmatory studies examining the cost-benefit relationship are needed. In the
      first 6 months, active as opposed to passive treatment results in improved
      outcomes. Specific exercise strategies have not been studied. For those with
      symptoms lasting more than 6 months, percutaneous radio-frequency neurotomy can
      provide pain relief for many months in those responding to blind local anesthetic
      facet blocks. Intra-articular corticosteroids are ineffective. Uncontrolled
      trials suggest that multimodal rehabilitation programs result in improved overall
      function. The overall prognosis for recovery has varied considerably across
      studies. Such variability is likely due to differences in case identification
      methods and whether outcome is assessed in terms of symptoms or the receipt of
      financial compensation for injury. The impact on prognosis of both collision- and
      patient-related factors is also reviewed.

PMID- 15170610
TI  - Canine inflammatory myopathy: analysis of cellular infiltrates.
AB  - Inflammatory myopathies (IMs) occur relatively frequently in dogs, and, with the
      exception of masticatory muscle myositis (MMM), have not been characterized. This
      study analyzed the distribution and types of cellular infiltrates in 21 cases of
      generalized IM, 3 cases of focal IM (MMM), and 1 case with features of both
      generalized and focal IM, using a panel of monoclonal antibodies to cell surface
      markers. In generalized IM, mononuclear cells showed an endomysial and perimysial
      distribution with invasion of non-necrotic fibers similar to human IM. T
      lymphocytes with T-cell receptor (TCR)alphabeta predominated. Distinct
      differences were seen in MMM including prominent B-cell infiltration, dendritic
      cells and macrophages in greater numbers than T cells, and numerous T cells with
      TCRgammadelta. Thus, generalized IM and MMM appear to be distinct diseases with
      different mechanisms. Canine generalized IM may be an important animal model for
      human IM.

PMID- 15170611
TI  - A novel central motor conduction abnormality in D90A-homozygous patients with
      amyotrophic lateral sclerosis.
AB  - Patients with amyotrophic lateral sclerosis (ALS) who are homozygous for the D90A
      SOD1 mutation have been noted to have central motor abnormalities distinct from
      those of patients with idiopathic ALS. We stimulated the motor cortex of ten
      patients homozygous for the D90A SOD1 mutation, using transcranial magnetic
      stimulation (TMS), and recorded the response evoked in the right first dorsal
      interosseous muscle when the muscle was at rest and when voluntarily active. A
      subgroup of patients had two distinct evoked responses when the cortex was
      stimulated at high intensity with the muscle at rest. When the muscle was
      modestly contracted, the first of these responses disappeared, whereas the second
      response was facilitated. Both fast and slow components of the corticospinal
      tract were usually intact and excited by TMS in these patients. We propose that
      there is an abnormality of intracortical or intraspinal inhibition in a subgroup
      of D90A SOD1 ALS patients, which suppresses fast-conducted activity when the
      muscle is active. Apart from further defining the phenotype of familial ALS,
      these findings may have importance in understanding the pathogenesis of central
      motor abnormalities in these patients.

PMID- 15170612
TI  - Functional activity and expression of inducible nitric oxide synthase (iNOS) in
      muscle of the isolated distal colon of mdx mice.
AB  - The inducible isoform of nitric oxide (NO) synthase (iNOS), expressed in
      endothelium, epithelium, and inflammatory cells, produces a large amount of NO.
      Previous studies on mouse intestine indicate that a muscular iNOS may have a role
      in the storage of intraluminal content. In this study we investigated the
      presence and function of iNOS in the colonic smooth muscle cells of 2- and 12
      month-old dystrophic (mdx) mice. By using an in vitro isovolumic technique, and
      immunohistochemical and Western blot analysis, we demonstrated that iNOS is
      expressed and active in the smooth muscle cells of normal mouse and defective in
      young adult (2-month-old) mdx mice. Therefore, an altered activity of the muscle
      iNOS might explain the motility disorders observed in the colon of mdx mice and,
      from a clinical point of view, the impairment of intestinal function in
      dystrophic patients.

PMID- 15170613
TI  - Influence of repetitive hand movements on intracortical inhibition.
AB  - Repetitive movements have been reported to induce task-specific changes of
      intracortical inhibition and facilitation, but the mechanism operating shortly
      after hand movement is unclear. Transcranial magnetic single and paired stimuli
      (2 ms) were applied to 15 healthy subjects at rest and 1 s after repetitive
      (every 6 s) active and passive hand extensions. Motor evoked potentials (MEPs)
      were recorded from hand extensors (agonists) and flexors (antagonists). A strong
      overall inhibitory effect was observed after applying paired stimuli. In agonists
      only, active movements produced significantly larger MEPs. Inhibition, however,
      did not differ between active or passive movements and rest. This suggests that
      MEP increases produced by active movements in agonists are not caused by
      disinhibition, but are rather due to excitation (facilitation). This finding may
      also have implications for future studies evaluating the preferential activation
      of target muscles in physiotherapy.

PMID- 15170614
TI  - Comparison of continuous and discontinuous FK506 administration on autograft or
      allograft repair of sciatic nerve resection.
AB  - An immunosuppressant drug that also possesses neuroregenerative properties, FK506
      enhances the rate of axonal regeneration and improves recovery after nerve
      lesions. Nevertheless, prolonged immunosuppression may not be justified to assure
      the success of nerve regeneration. In this study, we compare the effects of
      continuous and discontinuous FK506 treatment on regeneration and reinnervation
      after sciatic nerve resection repaired with autologous or allogenic grafts in the
      mouse. For each type of repair, one group received FK506 (5 mg/kg) for 4 months,
      whereas a second group was treated with FK506 at 5 mg/kg for 5 weeks followed by
      3 mg/kg for 4 weeks; a control group received saline only. Functional
      reinnervation was assessed by noninvasive methods to determine recovery of motor,
      sensory, and autonomic functions in the hind paw over 4 months after operation.
      Morphological analysis of the regenerated nerves was performed at the termination
      of the study. Autografts and allografts treated with sustained FK506 (5 mg/kg)
      reached high levels of reinnervation and followed a course of recovery faster
      than controls. The numbers of myelinated fibers also were similar. Allografts
      without immunosuppression demonstrated a slower rate of regeneration, exhibiting
      lower final levels of recovery compared with other groups and containing fewer
      numbers of regenerating myelinated fibers. Withdrawal of immunosuppressant
      therapy resulted in a decline in the degree of reinnervation in all functions
      tested during the third month, with stabilization between the third and fourth
      months. The number of regenerated myelinated fibers in the group was
      significantly lower than in autografts. Thus, continuous or discontinuous FK506
      administration slightly accelerated the rate of reinnervation in autografts. In
      allograft repair, FK506 significantly enhanced both the rate and degree of
      regeneration and recovery, but its withdrawal resulted in graft rejection, a
      marked deterioration in function, and loss of regenerating fibers.

PMID- 15170615
TI  - Muscle-fiber conduction velocity estimated from surface EMG signals during
      explosive dynamic contractions.
AB  - Muscle-fiber conduction velocity (CV) was estimated from surface
      electromyographic (EMG) signals during isometric contractions and during short
      (150-200 ms), explosive, dynamic exercises. Surface EMG signals were recorded
      with four linear adhesive arrays from the vastus lateralis and medialis muscles
      of 12 healthy subjects. Isometric contractions were at linearly increasing force
      from 0% to 100% of the maximum. The dynamic contractions consisted of explosive
      efforts of the lower limb on a sledge ergometer. For the explosive contractions,
      muscle-fiber CV was estimated in seven time-windows located along the ascending
      time interval of the force. There was a significant correlation between CV values
      during the isometric ramp and explosive contractions (R = 0.75). Moreover, CV
      estimates increased significantly from (mean +/- SD) 4.32 +/- 0.46 m/s to 4.97 +/
      0.45 m/s during the increasing-force explosive task. It was concluded that CV
      can be estimated reliably during dynamic tasks involving fast limb movements and
      that, in these contractions, it may provide important information on motor-unit
      control properties.

PMID- 15170616
TI  - Measurement and reproducibility of strength and voluntary activation of lower
      limb muscles.
AB  - Accurate measurement of muscle strength and voluntary muscle activation is
      important in the assessment of disorders that affect the motor pathways or
      muscle. We designed a multipurpose system to assess the variability and
      reproducibility of isometric torque measurements obtained during maximal
      voluntary efforts of the knee flexor, knee extensor, ankle dorsiflexor, and ankle
      plantarflexor muscles on each side. It used two isometric myographs mounted on an
      adjustable frame. Measurements of maximal voluntary torque (range, 25-188 Nm)
      displayed low variability within a testing session and over five testing sessions
      (coefficient of variation range, 5-11%). We used the same equipment to measure
      voluntary activation of the triceps surae muscles. Voluntary activation, measured
      with a sensitive twitch interpolation method, increased with increasing voluntary
      contraction torque (P < 0.001) and was very high during maximal efforts (mean,
      97.8 +/- 2.1%; median, 98.5%). Furthermore, measurements of voluntary activation
      during maximal efforts were reproducible across testing sessions with very little
      variability (coefficient of variation, <2%). The myograph system and the testing
      procedures should allow accurate measurement of strength and voluntary drive in
      longitudinal patient studies.

PMID- 15170617
TI  - Functional relationships of central and peripheral muscle alterations in multiple
      sclerosis.
AB  - The functional implications of central motor impairment and peripheral muscle
      alterations in multiple sclerosis are unclear. Muscle strength, central and
      peripheral activation, and symptomatic fatigue were investigated in 16 patients
      with multiple sclerosis (MS) and 18 control subjects. Voluntary and electrically
      stimulated isometric contractions were obtained from the ankle dorsiflexor
      muscles. Maximal voluntary contraction (MVC) was 27% lower in MS patients than
      controls, although electrically stimulated force was similar. Muscle fat-free
      cross-sectional area (CSA) was similar in both groups. These data indicate
      central activation impairment in MS. Such impairment in MS was further
      demonstrated by decreased foot-tap speed, rate of voluntary force development,
      and central activation ratio. Peripheral activation changes in MS patients were
      modest. Although stimulated tetanic force was similar, force relaxation was
      slower in MS patients compared to controls, resulting in a left-shifted force
      frequency relationship in MS. Motor function changes were not associated with
      fatigue but were associated with impaired ambulation. Thus, weakness and walking
      impairment, but not fatigue, were related to impaired central activation in MS.
      These findings may help optimize rehabilitation strategies designed to improve
      function in persons with MS.

PMID- 15170619
TI  - Is muscle spindle proprioceptive function spared in muscular dystrophies? A
      muscle tendon vibration study.
AB  - Muscular dystrophies (MDs) are characterized by the degeneration of skeletal
      muscle fibers. The aim of the present study was to determine whether the
      intrafusal fibers of muscle spindles are also affected in MD. The functional
      integrity of muscle spindles was tested by analyzing their involvement in the
      perception of body segment movements and in the control of posture. Twenty MD
      patients (4 with dystrophinopathy, 5 with myotonic dystrophies, 5 with
      fascioscapulohumeral MD, and 6 with limb-girdle dystrophies) and 10 healthy
      subjects participated in the study. The MD patients perceived passive movements
      and experienced illusory movements similar to those perceived by healthy subjects
      in terms of their direction and velocity. Vibratory stimulation applied to the
      neck and ankle muscle tendons induced postural responses in MD patients with
      spatial and temporal characteristics similar to those produced by healthy
      subjects. These results suggest that the proprioceptive function of muscle
      spindles is spared in muscular dystrophies.

PMID- 15170618
TI  - Receptor for advanced glycation endproduct (RAGE)-mediated nuclear factor-kappaB
      activation in vasculitic neuropathy.
AB  - Binding of ligands to the receptor for advanced glycation endproducts (RAGE)
      results in activation of the proinflammatory transcription factor nuclear factor
      kappaB (NF-kappaB) and subsequent expression of NF-kappaB-regulated cytokines. In
      order to determine whether engagement of RAGE contributes to the pathogenesis of
      vasculitic neuropathy, we studied the presence of the RAGE ligand N(epsilon)
      (carboxymethyl)lysine (CML), the receptor itself, NF-kappaB, and interleukin-6
      (IL-6) in sural nerve biopsies of 12 patients with vasculitic neuropathies and 12
      controls. In the patients, CML, RAGE, NF-kappaB, and IL-6 were localized in
      mononuclear cells, epineurial and endoneurial vessels and the perineurium. CML,
      RAGE, NF-kappaB, and IL-6 were expressed by CD4(+), CD8(+), and CD68(+) cells
      invading the nerves. Controls showed only weak staining. These data suggest that
      the RAGE pathway plays a critical proinflammatory role in vasculitic neuropathy.

PMID- 15170620
TI  - Clinical and genetic description of a family with Charcot-Marie-Tooth disease
      type 1B from a transmembrane MPZ mutation.
AB  - Mutations in the myelin protein zero gene (MPZ) are associated with certain
      demyelinating neuropathies, and in particular with Charcot-Marie-Tooth disease
      type 1B (CMT1B), Dejerine-Sottas syndrome, and congenital hypomyelination. MPZ
      mutations affecting the protein's transmembrane domain are generally associated
      with more severe phenotypes. We describe a family with mild CMT1B associated with
      a transmembrane MPZ mutation. Sequence analysis identified a G-to-C transversion
      at nucleotide 1064, predicting a glycine-to-arginine substitution in codon 163
      (G163R) of MPZ. This report furthers the understanding of the clinical and
      electrophysiological manifestations of MPZ mutations.

PMID- 15170621
TI  - Cutaneous silent period in hand muscle is evoked by laser stimulation of the
      palm, but not the hand dorsum.
AB  - Painful electrical stimulation of the fingers evokes an inhibitory response in
      hand muscles (cutaneous silent period, CSP). The aim of this study was to
      determine whether purely nociceptive thermal stimuli applied to the hand evoke a
      CSP. High-intensity laser pulses (205 +/- 44 mJ) were delivered to the dorsum and
      palm of the hand in five volunteers. Electromyographic signals were recorded from
      the ipsilateral first dorsal interosseous muscle. We then compared the laser
      evoked CSP with the CSP induced by electrical stimulation. A clear laser CSP
      (latency 90 +/- 7 ms) was evoked in all subjects when laser pulses were applied
      to the palm of the hand, whereas no response was recorded after stimulation of
      the dorsum. Electrical stimulation of both the dorsum and the palm evoked a CSP
      (latency 65 +/- 5 ms), although the reflex threshold was significantly lower
      after stimulation of the palm. This study confirms that the CSP is a nociceptive
      response specific to limbs that grasp. In humans, palm nociceptors are probably
      more functionally effective than dorsal nociceptors in inducing the hand-muscle
      inhibition that interrupts hand prehension (so that a potentially noxious source
      is dropped) before proximal muscles withdraw the limb.

PMID- 15170622
TI  - Myositis in a patient with large granular leukocyte leukemia.
AB  - We describe the case of a 58-year-old patient with subacute progressive weakness
      in both legs accompanied by recurrent opportunistic infections. White cell count
      was normal, but immunophenotyping revealed an increased number of CD8(+) T cells
      and deficiency of natural killer cells, B cells, and CD4(+) T cells in the
      peripheral blood. Large granular leukocyte (LGL) leukemia was diagnosed based on
      a clonal T-cell receptor rearrangement. Muscle biopsy demonstrated severe
      myositis with extensive CD8(+) T-cell infiltrates. Since no evidence of microbial
      muscle infection was found, autoimmune myositis was diagnosed. Immunosuppressive
      treatment resulted in clinical improvement and normalization of creatine kinase
      (CK) serum levels. The immunological phenotype of the patient and the positive
      response to treatment adds further to the concept that CD8(+) T cells mediate
      disease in autoimmune myositis.

PMID- 15170623
TI  - Electrophysiological evaluation of the supraclavicular nerves.

PMID- 15170624
TI  - SARS coronavirus induces apoptosis in Vero E6 cells.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infectious disease. Its
      etiological agent has been convincingly identified as a new member of family
      Coronaviridae (SARS-CoV). It causes serious damage to the respiratory system yet
      the mechanism is not clear. Infection-induced apoptosis or necrosis is suspected
      but no direct evidence for this yet exists. To date, Vero E6 cells are the only
      cell line that could be used to replicate the virus with obvious CPE (cytopathic
      effect) in vitro. It is known for some viruses (including members of family
      Coronaviridae) that CPE can be caused either by virus-induced apoptosis (active
      death) or cell necrosis (passive death). In this study, we examined the apoptosis
      in the SARS-CoV infected Vero E6 cells. Indeed, the results do show that the CPE
      was induced by apoptosis rather than necrosis, shown by typical DNA
      fragmentation, through the existence of apoptotic bodies and swollen
      mitochondria. This observation has some implications for the SARS-CoV
      pathogenicity: SARS-CoV does induce apoptosis in cell cultures and might have the
      same effect in vivo, responsible for the severe damage of the respiratory system.

PMID- 15170625
TI  - The life cycle of SARS coronavirus in Vero E6 cells.
AB  - The aim of the study was to establish the life cycle of severe acute respiratory
      syndrome-associated coronavirus (SARS CoV) in host cells and determine the
      pathogenesis of SARS. Vero E6 cells (African green monkey kidney cells) were
      inoculated with SARS coronavirus for 3, 7, 24, 48, and 72 hr, respectively, and
      were observed under electron microscope. It was found that the SARS coronavirus
      entered the cells through membrane fusion instead of endocytosis, and then the
      nucleocapsids assembled in the RER and matured by budding into the smooth
      vesicles, which were derived from the Golgi apparatus. The smooth vesicles fused
      with the cell membrane, and the mature particles were released. A special
      phenomenon was that some virus-like particles appeared in the nucleus. We propose
      a scheme of the life cycle of SARS coronavirus and discuss the mechanism of its
      replication in Vero E6 cells.

PMID- 15170626
TI  - Evaluation of antibody responses against SARS coronaviral nucleocapsid or spike
      proteins by immunoblotting or ELISA.
AB  - Severe acute respiratory syndrome (SARS)-CoV is a newly emerging virus that
      causes SARS with high mortality rate in infected people. To study the humoral
      responses against SARS-CoV, we evaluated nucleocapsid (N) and spike (S) proteins
      specific antibodies in patients' sera by Western blotting and enzyme-linked
      immunosorbent assay (ELISA). Recombinant N and S proteins of SARS-CoV were
      purified from transformed E. coli. Serum specimens from 40 SARS-CoV-infected
      patients in the convalescent phase were analyzed by Western blotting using the
      purified antigens. Serial serum specimens from 12 RT-PCR-confirmed SARS patients
      were assayed by ELISA using the recombinant N protein as coated antigen. By
      Western blotting, 97.5% of the SARS patients were positive for N protein-specific
      antibodies whereas only 47.5% of the samples were positive for S protein-specific
      antibodies. Using N protein-based ELISA, 10 out of the 12 patients were positive
      for N protein-specific antibodies and 6 of them showed seroconversion at mean of
      16 days after onset of fever. Immunoblotting was useful for detecting the humoral
      immune response after SARS-CoV infection. Antibodies against SARS-CoV N protein
      appear at the early stage of infection, therefore, N protein-based ELISA could
      serve as a simple, sensitive, and specific test for diagnosing SARS-CoV
      infection.

PMID- 15170627
TI  - Failure and success of HIV tests for the prevention of HIV-1 transmission by
      blood and tissue donations.
AB  - French blood banks recently implemented nucleic acid testing (NAT) of all blood
      donations to reduce the risk of HIV transmission during the pre-seroconversion
      period. For tissue donation, HIV infection screening relies on HIV p24 antigen
      and anti-HIV-1 and 2 antibody detection. In this report, two related cases of
      infectious donations are described from a cornea donor during the
      preseroconversion window who was infected by an HIV antibody and NAT negative
      blood donor. After investigation, the blood donor was found to be herself in the
      preseroconversion window. Two months after donation, she was found to be HIV
      positive. The residual risk of HIV infectious blood donations since NAT has been
      introduced is estimated to be lower than one out of 2.5 millions. Individual NAT
      instead of minipool testing would not increase significantly the blood
      transfusion safety. In contrast, introduction of NAT should be considered to
      increase tissue donation safety as soon as such screening will be possible
      technically.

PMID- 15170629
TI  - Downregulation of CXCR5 in CD27- B cells of HIV-1 infected patients.
AB  - The CD27(-) (naive) B cells of HIV-1 infected patients have been shown to be
      increased in frequency and to be activated, as indicated by high CD38 expression
      on the cell surface. CXCR5, a B cell chemokine receptor, is expressed on
      circulating CD27(-) (naive) B cells and plays a pivotal role in peripheral B cell
      development. To investigate the effect of HIV-1 infection on the expression of
      this chemokine receptor on naive B cells, the expression level of CXCR5 on CD27(
      ) B cells was examined in 19 drug-naive HIV-1 infected patients, 27 HAART-treated
      patients, and 20 controls. CXCR5 expression on CD27(-) B cells was significantly
      lower in drug-naive patients than in HAART-treated patients and controls (P <
      0.01). CD27(-) B cells with high CD38 expression exhibited low CXCR5 expression.
      The CXCR5 expression level on CD27(-) B cells recovered to within the normal
      range after effective antiretroviral therapy. These findings suggested that HIV-1
      infection induces a remarkable phenotypic alteration of naive B cells and that
      the activated naive B cells found in HIV-1 infection downregulate CXCR5 on their
      surface. Impaired homing of naive B cells may contribute to HIV-1 induced
      immunological deficiencies.

PMID- 15170628
TI  - Long-term suppression of plasma viremia with highly active antiretroviral therapy
      despite virus evolution and very limited selection of drug-resistant genotypes.
AB  - HIV-1 evolution and the possible emergence of mutations associated with
      resistance to antiretroviral inhibitors have been evaluated in a cohort of sixty
      three patients successfully treated with highly active antiretroviral therapy
      (HAART). The patients under effective HAART were recruited in three different
      hospitals in Spain, and none of them had been treated (naive) before entering
      this study. HIV-1 RNA levels, CD4+, and CD8+ T-cell counts were determined, and
      nucleotide sequences of proviral regions encoding protease and reverse
      transcriptase (RT) were obtained for longitudinal blood samples spanning a mean
      follow-up period of 88 weeks. Phylogenetic reconstructions and calculations of
      genetic distances among the different sequences of each patient were performed.
      All except one of the patients under study showed an early and sustained decrease
      in plasma HIV-1 RNA to levels that were below 200 copies/ml. The plasma viral
      decline paralleled a significant increase in the CD4+ T-lymphocyte counts. Amino
      acid sequence analyses revealed the occurrence of mutations associated with
      antiretroviral resistance in nine patients (14.3%) during HAART treatment, that
      in some cases could be attributed to excess G to A transitions. In six of the
      nine patients, the mutations conferred resistance to inhibitors administered in
      the treatment regime, although the mutations did not result in treatment failure.
      Sequence comparisons revealed viral evolution during the period of treatment in
      47.5% of the patients. The results indicate successful suppression of HIV-1 under
      HAART for extended time periods, indistinguishable for patients in which evidence
      of virus evolution could or could not be documented.

PMID- 15170630
TI  - Induction of HIV-specific antibody response and protection against vaginal SHIV
      transmission by intranasal immunization with inactivated SHIV-capturing
      nanospheres in macaques.
AB  - We have previously reported that concanavalin A-immobilized polystyrene
      nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that
      intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS)
      induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to
      evaluate the protective effect of immunization, each three macaques was
      intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency
      virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged
      with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal
      anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized
      macaques. After intravaginal challenge, one of the three macaques in each of the
      Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of
      infected macaque in SHIV-NS-immunized macaques was substantially less than that
      in unimmunized control macaque and reached below the detectable level. However,
      it could not be determined whether intranasal immunization with SHIV-NS is
      effective in giving complete protection against intravaginal challenge. To
      explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques
      were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all
      macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA
      loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma
      anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS
      immunized macaques than in the controls. The rapid antibody responses having
      neutralizing activity might contribute to the clearance of the challenge virus.
      Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and
      systemic challenges with SHIV KU-2.

PMID- 15170632
TI  - Immunoglobulin GM and KM genotypes in hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a major health problem, affecting over 170 million
      people worldwide. HCV causes a wide spectrum of liver disease, varying from
      persistent to asymptomatic infection. To evaluate the role of immunoglobulin (Ig)
      GM and KM genes in HCV infection, 191 HCV-infected Thai subjects were studied.
      These included 43 individuals with transient HCV infection and 148 individuals
      with persistent chronic HCV infection. The controls consisted of 134 healthy
      individuals. Several GM and KM alleles were determined by polymerase chain
      reaction-based methods. The frequency of G1M(f) homozygotes was lower (52.4% vs.
      64.2%, P = 0.03) and the frequency of G1M(z) homozygotes was higher (10.5% vs.
      3.7%, P = 0.02) in patients than the respective frequencies in controls. These
      results suggest that GM genotypes make a significant contribution to the risk of
      acquiring HCV infection.

PMID- 15170631
TI  - Genetic analysis of hepatitis A virus isolates from Brazil.
AB  - A limited number of hepatitis A virus (HAV) isolates from South America have been
      characterised at the genomic level. IgM anti-HAV positive serum samples collected
      from patients with hepatitis A living in the five geographical regions of Brazil
      (North, Northeast, Central, South, and Southeast) were used to obtain HAV
      isolates and determine their genetic relatedness. Of the 232 case isolates,
      sequence data were obtained from the VP1/2A junction region of the HAV genome.
      All isolates were classified in genotype I; 231 belonged to subgenotype IA, and
      one to subgenotype IB. HAV isolates from four States formed distinct clusters of
      highly related sequences. However, isolates from other states did not cluster and
      the sequences from those states were intermingled with sequences found in the
      other states. The amino acid sequences of all but two isolates showed a Leu -->
      Ile substitution at position 42 in the 2A protein. This substitution appeared to
      be a characteristic geographic fingerprint of HAV sequences within Brazil.

PMID- 15170633
TI  - High rate of spontaneous clearance of acute hepatitis C virus genotype 3
      infection.
AB  - Treating acute hepatitis C with interferon alpha prevents chronicity in nearly
      all cases when therapy is initiated within 3 months after infection. However, 15
      50% of untreated patients may clear the hepatitis C virus (HCV) spontaneously.
      Therefore, factors are needed to identify patients prior to therapy who have a
      higher or lower risk for developing a chronic course to avoid unnecessary
      treatment. The role of the HCV genotype for spontaneous recovery from acute
      hepatitis C has been discussed controversially. In the year 2002, all 1,176 new
      incoming prisoners in a Northern German prison for young men (age 16-24) were
      screened for anti-HCV antibodies and 92 tested positive. Ninety eight percent of
      these reported i.v.-drug abuse for a median of 32 months prior to imprisonment.
      HCV-RNA negative individuals (21%) were serotyped and HCV-RNA positive patients
      were genotyped. The prevalence of HCV genotype 3 was significantly higher among
      individuals who had cleared HCV spontaneously as compared to chronically infected
      patients (86% vs. 38%; P = 0.002). Ninety three percent of individuals exposed to
      HCV genotype 1 but only 63% of individuals exposed to genotype 3 experienced a
      chronic course of the infection (P = 0.006). Thus, acute infection in young
      Caucasian men with HCV genotype 3 leads more often to spontaneous clearance than
      infection with HCV genotype-1. Considering also the high chance of successful
      treatment of chronic HCV genotype 3 infection with pegylated-interferon in
      combination with ribavirin, we suggest not to treat acute hepatitis C genotype 3
      infection early but rather to wait at least 3 months after the onset of symptoms
      when chronicity becomes likely.

PMID- 15170634
TI  - The predictive value of core antigen testing for the management of hepatitis C
      patients receiving pegylated interferon/ribavirin treatment.
AB  - A new quantitative marker of HCV viremia based on the detection of the core
      antigen of the virus has recently become commercially available in Europe. The
      usefulness of this test was examined for the management of patients treated with
      pegylated interferon/ribavirin. One hundred twenty-eight pegylated
      interferon/ribavirin treated patients were studied. Serum samples were available
      at baseline, week 4 and week 12 time-points, respectively. Core antigen was
      quantified using the trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ). For
      all genotypes at week 4, the positive and negative predictive values of HCV core
      antigen were 81.4 and 92.9%, respectively, while at week 12 they were 67.9 and
      100%, respectively. These predictive values varied substantially according to
      viral genotype. Among patients with a negative core antigen level (<1.5 pg/ml) at
      week 12, only 33% of those who were positive at week 4 achieved a sustained
      virological response whereas 85% of those who were already negative did (P <
      0.001). The core antigen assay may be used at week 4 and week 12 to distinguish
      patients who will achieve a sustained virological response from those who will
      relapse/breakthrough. This assay is a new reliable alternative for early
      prediction of virological non-response in patients treated with pegylated
      interferon/ribavirin.

PMID- 15170635
TI  - Evaluation of a total hepatitis C virus (HCV) core antigen assay for the
      detection of antigenaemia in anti-HCV positive individuals.
AB  - A new, sensitive enzyme immunoassay has been developed for detecting and
      quantifying total hepatitis C virus (HCV) core antigen in anti-HCV positive or
      negative sera ("trak-C", Ortho Clinical Diagnostics, Raritan, NJ). The purpose of
      this study was to evaluate the performance of trak-C as an additional laboratory
      diagnostic marker of viraemia. The performance was compared to HCV-RNA detection
      in the "screening" of sera from a large heterogeneous population of hospitalised
      patients and outpatients. Six hundred and eighteen anti-HCV negative sera, 405
      anti-HCV positive/HCV-RNA negative sera, 604 anti-HCV positive/HCV-RNA positive
      sera and 67 anti-HCV negative sera containing antigens or antibodies potentially
      interfering with the performance of the assay were analysed. Supplemental HCV
      antibody testing was performed using a commercial strip immunoblot assay. HCV-RNA
      was investigated using a qualitative commercial assay. A quantitative commercial
      RT-PCR was used for the analysis of selected samples. Sensitivity and specificity
      values were 94.7 and 100%, respectively. The latter was also confirmed when anti
      HCV negative samples containing potentially interfering antigens/antibodies were
      examined. Sensitivity below 100% was probably due to an antigenaemia below the
      detection limit of trak-C. Besides, because 65.6% of HCV-RNA positive/trak-C
      negative samples presented specific antibodies against all four RIBA antigens,
      the hypothesis was raised that, in some cases, the dissociation step efficiency
      could be sub-optimal. In conclusion, trak-C seems suitable for identifying HCV
      infection on large based populations. It is a rapid to perform, reliable and
      specific assay that can be adapted to any laboratory setting.

PMID- 15170636
TI  - Genetic analysis of Crimean-congo hemorrhagic fever virus in Iran.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a
      tick-borne virus in the family Bunyavridae. The disease occurs in parts of
      Africa, Asia, Middle East, and Eastern Europe. During recent years, an increasing
      number of human CCHF cases have been diagnosed in Iran, but very little
      information is available on the prevalence and genetic diversity of CCHFV in
      Iran. In the present study, CCHF virus (CCHFV) isolates from nine Iranian
      patients infected during 2002 were examined genetically. Nucleotide sequencing of
      the S- and M-segments, encoding the nucleocapsid protein (NP) and the
      glycoproteins, respectively, revealed that the different isolates were related
      closely to each other with nucleotide sequence identities exceeding 98% for both
      S- and M-segments. Phylogenetic analysis of partial S-segment nucleotide
      sequences showed that the viruses clustered along with strains from Pakistan and
      Madagascar in one distinct lineage. Phylogenetic analysis also demonstrated that
      the Iranian isolates examined in this study and the previously published CCHFV
      strain ArTeh193-3 clustered into different genetic groups, indicating that at
      least two genetic lineages of CCHFV could be co-circulating in Iran.

PMID- 15170637
TI  - Clinically-based determination of safe DNAemia cutoff levels for preemptive
      therapy or human cytomegalovirus infections in solid organ and hematopoietic stem
      cell transplant recipients.
AB  - Transplantation Centers using human cytomegalovirus (HCMV) antigenemia-based
      preemptive therapy will need to replace in the near future the antigenemia assay
      with a more standardized and automatable assay, such as a molecular assay
      quantifying HCMV DNA in blood (DNAemia). Thus, in view of replacing antigenemia
      with clinically safe cutoff values, DNAemia levels corresponding to antigenemia
      cutoffs guiding HCMV preemptive therapy were determined retrospectively in solid
      organ and hematopoietic stem cell transplant recipients (HSCTR) using an "in
      house" quantitative PCR (QPCR) method. Since preemptive therapy had prevented
      appearance of HCMV disease in all patients tested, DNA cutoffs determined
      retrospectively had to be considered as safe clinically as antigenemia cutoffs
      used prospectively. However, in solid organ transplant recipients (SOTR),
      initiating preemptive therapy upon an antigenemia cutoff of 100 pp65-positive
      leukocytes, a DNAemia cutoff of 300,000 copies/ml blood had positive and negative
      predictive values of >90%, indicating that a DNAemia cutoff could achieve, in
      terms of prevention of HCMV disease, the same clinical results as the antigenemia
      cutoff. In HSCTR, initiating preemptive therapy upon first antigenemia
      positivity, a DNAemia cutoff of 10,000 copies/ml blood had a positive predictive
      value of >90%, indicating that the great majority of patients treated under the
      antigenemia guidance would have been treated also using this DNA cutoff. On the
      other hand, the negative predictive value of 28.6% indicated that two out of
      three HSCTR had been treated under the antigenemia guidance having the same
      levels of viral DNA as the untreated patients. The data suggest that a
      quantitative cutoff could be adopted as a guiding criterion for preemptive
      therapy also in HSCTR. Regression analysis allowed to determine the DNAemia
      (corresponding to QPCR) cutoff values for two commercial assays tested both in
      solid organ and HSCTR. Retrospective DNAemia cutoff values will be verified for
      safety in prospective trials.

PMID- 15170638
TI  - Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice
      infected by dengue virus.
AB  - Activation and expansion of dengue virus-specific T cells and abnormal liver
      functions in dengue patients have been documented. However, it remains to be
      determined whether T cells are involved in the pathogenic mechanism of dengue
      virus infection. In this study, immunocompetent C57BL/6 mice were employed to
      study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU
      dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core
      RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different
      time points after infection. Splenic T cells were activated as evidenced by their
      expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection.
      Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production
      coordinately peaked at day 5. Coincided with the peak of splenic T cell
      activation was hepatic lymphocyte infiltration and elevation of liver enzymes.
      Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell
      ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell
      infiltration and liver enzyme levels increased sharply. The infiltrating hepatic
      CD8(+) T cell to CD4(+) T cell ratio increased to 5.8/1. A strong correlation was
      found between T cell activation and hepatic cellular infiltration in
      immunocompetent mice infected with dengue virus. The kinetics of liver enzyme
      elevation also correlated with that of T cell activation. These data suggest a
      relationship between T cell infiltration and elevation of liver enzymes.

PMID- 15170639
TI  - Epstein-Barr virus (EBV) infection and expression of the interleukin-12 family
      member EBV-induced gene 3 (EBI3) in chronic inflammatory bowel disease.
AB  - Herpesviruses have been suggested as possible etiological agents of ulcerative
      colitis and Crohn's disease. Recently, increased numbers of Epstein-Barr virus
      (EBV)-infected cells have been detected in ulcerative colitis as compared to
      Crohn's disease. Interestingly, expression levels of the EBV-induced gene 3
      (EBI3), a molecule belonging to the interleukin (IL)-12 family, have also been
      reported to be elevated in ulcerative colitis as compared to Crohn's disease. To
      test the hypothesis that these observations might be interrelated, ileocolic
      resection specimens were examined from 16 patients with ulcerative colitis and
      from 20 patients with Crohn's disease. The presence of EBV-infected cells and of
      EBI3-expressing cells was determined quantitatively by in situ hybridisation and
      immunohistochemistry, respectively. Larger number of EBV-infected cells were seen
      in areas of active inflammation of ulcerative colitis and Crohn's disease as
      compared to areas of inactive inflammation. However, there was no statistically
      significant difference between ulcerative colitis and Crohn's disease. Numbers of
      EBI3-expressing cells were increased in areas of active inflammation of
      ulcerative colitis and Crohn's disease but again there was no statistically
      significant difference between the two diseases. Double labelling experiments
      showed that EBI3 expression occurred only in a small minority of EBV-infected
      cells in ulcerative colitis and Crohn's disease. These results suggest that
      increased numbers of EBV-infected cells in areas of active inflammatory bowel
      disease (IBD) are secondary to influx or local proliferation of inflammatory
      cells and do not contribute significantly to local production of EBI3. Assessment
      of the possible role of EBI3 of the pathogenesis of ulcerative colitis or Crohn's
      disease requires information regarding the expression of other IL-12 family
      members.

PMID- 15170641
TI  - Diversity of enteric viruses detected in patients with gastroenteritis in a
      tertiary referral paediatric hospital.
AB  - The genetic diversity of enteric viruses co-circulating in a cohort of patients
      with viral gastroenteritis in a large tertiary paediatric hospital in London, UK,
      was determined. Multiple strains of noroviruses (NV), sapoviruses (SV) and
      astroviruses (HAsV) were detected in these patients, indicating the likelihood of
      multiple introductions from different sources, possible sub-clinical infections
      and simultaneous infection with different viruses in immunocompromised and other
      patients. Routine screening of immunocompromised patients and infection control
      procedures are important to prevent nosocomial infection.

PMID- 15170640
TI  - Isolation and molecular identification of echovirus 13 isolated from patients of
      aseptic meningitis in Korea, 2002.
AB  - During 2002, several epidemics of aseptic meningitis were attributed to echovirus
      13 in Korea. The causative agents of these outbreaks were isolated and identified
      using rhabdosarcoma cells, HEp-2 and Buffalo green monkey kidney cells, and a
      neutralization test using monospecific antiserum. Fifty-four echovirus 13
      isolates were isolated from patients with aseptic meningitis in the provinces,
      Seoul, Kyonggi, Gwangju, Jeonju, Busan, and Ulsan. Symptoms associated with
      aseptic meningitis infection in patients included the occurrence of headaches and
      mild fever. Molecular characterization of echovirus 13 samples was achieved by
      sequence and phylogenetic analyses on partial VP1 sequences from 20 Korean
      isolates and 10 foreign isolates listed in Genbank. Minor variation was observed
      among the Korean isolates, which formed a unique cluster with isolates of German
      and Japanese origin. The marked similarities between isolates could be attributed
      to a relatively recent arrival of the virus in Korea. This is the first such
      investigation of aseptic meningitis caused by echovirus 13 on the Korean
      peninsula.

PMID- 15170642
TI  - Enterovirus infections with beta-cell tropic strains are frequent in siblings of
      children diagnosed with type 1 diabetes children and in association with elevated
      levels of GAD65 antibodies.
AB  - Enterovirus infections have been associated with type 1 diabetes in a number of
      reports. Recent prospective studies have suggested that enterovirus infections
      initiate the autoimmune process. Variation in virulence and replication pattern
      between strains of a serotype has also been shown. The aim was to study if there
      were specific Coxsackievirus strains that were associated more often with the
      type 1 diabetes children than with controls and/or siblings and to analyse if
      there was any time-relationship between such infections and the appearance of
      antibodies against glutamic acid decarboxylase 65 (GAD65). In the present study,
      serum was tested from newly diagnosed type 1 diabetes children, their siblings
      and matched controls for neutralising antibodies against different strains of
      Coxsackievirus B (CBV). Tests for the presence of antibodies against GAD65 in the
      same groups were also carried out. Newly diagnosed type 1 diabetes children
      revealed higher titres of neutralising antibodies against a strain of
      Coxsackievirus B4 (CBV-4, VD2921) that has been shown to cause persistent
      infection in human pancreatic islet cells. The type 1 diabetes child and its
      sibling often encountered the same infection. Among the former, 16 of 27 (59%)
      had a significant rise in neutralising antibodies. Eight of the type 1 diabetes
      children had such a rise against a recombinant strain, V89 4557. Among the
      siblings 10 of 13 (77%) had significant titre increases. Among the type 1
      diabetes children, increasing neutralising titres was associated positively with
      increasing antibody levels against GAD65. All siblings with antibodies against
      GAD 65 had significant titre increase against any of the CBV strains.

PMID- 15170643
TI  - An outbreak of gastroenteritis during school trip caused by serotype G2 group A
      rotavirus.
AB  - Between May14 and 18, 2001, there was an outbreak of acute gastroenteritis
      involving 45 school children out of a total of 107 (aged 11-12 years) attending a
      3-day school trip. The epidemic curve characterized by a rapid onset and decline
      with a single peak incidence over a 5-day period resembled the pattern typical of
      a food-borne gastroenteritis outbreak. Epidemiological and virological
      investigations concluded, however, that this outbreak was caused by a single
      strain of serotype G2 group A rotavirus spreading to schoolmates from the primary
      case-pupil who had already been ill at the start of the trip. Efficient person-to
      person transmission was likely to have occurred due to prolonged and close
      contacts under the conditions typical of such school trips. This study emphasizes
      the importance of including group A rotavirus infection as a possible cause of
      gastroenteritis outbreaks even in older children and adults.

PMID- 15170644
TI  - Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated
      form and characterization of cases with chromosomally integrated HHV-6 DNA.
AB  - We obtained 7,566 peripheral blood mononuclear cell (PBMC) samples from 2,332
      individuals and screened them for human herpesvirus infection. We identified five
      individuals who persistently harbored high copy numbers of human herpesvirus 6
      (HHV-6) DNA in their PBMCs. HHV-6 DNA was also detected in other somatic tissues
      of these individuals. Five additional cases were identified among their family
      members. For two of these families, chromosomally integrated HHV-6 DNA (CIHHV-6)
      was detected in the PBMCs by fluorescence in situ hybridization. The prevalence
      of CIHHV-6 among all the subjects was 0.21%. The HHV-6 DNA was variant B in four
      families and variant A in one family. Antibodies to immediate early antigen and
      glycoprotein B were detected in 57 and 14% of individuals with CIHHV-6 and in 0
      and 60% of healthy volunteers without CIHHV-6, respectively. HHV-6 could not be
      isolated from PBMCs with CIHHV-6. These cases shared no clinical features, and
      included three healthy individuals. Our data suggest that CIHHV-6 is rare but
      detectable in the general population and that hereditary transmission is one of
      the routes of HHV-6 transmission.

PMID- 15170645
TI  - Positively charged synthetic peptides from structural proteins of
      papillomaviruses abrogate human papillomavirus infectivity.
AB  - Human papillomavirus (HPV) virus-like particles (VLP) and synthetic peptides
      corresponding to positively-charged sequences of the major and minor capsid
      proteins were tested for their efficacy in inhibiting the infectivity of HPV 31
      pseudovirions by blocking virus entry into cells. A greater than 80% reduction of
      transfection was observed with one HPV-31 peptide at a concentration of 10
      microg/ml. Moreover, the blocking was not type-specific since similar reduction
      in transfection was observed with peptides from other HPV types at a
      concentration of 60 microg/ml. This concentration was non-toxic for the cells.
      These findings indicate that some of the positively-charged sequences of the L1
      and L2 HPV capsid proteins of papillomavirus are compounds that might be locally
      active against sexually transmitted papillomavirus. The findings provide further
      evidence that cellular glycosamino-glycans (GAGs) are functional receptors for
      HPVs.

PMID- 15170646
TI  - Human papillomavirus in a rural community in Zimbabwe: the impact of HIV co
      infection on HPV genotype distribution.
AB  - Cervical cancer is a leading cause of cancer-related deaths in developing
      countries, and the human papillomavirus (HPV) is linked etiologically to cervical
      cancer. Hence, a vaccine which prevents HPV-associated cervical cancer would have
      the most impact in developing countries, including the African continent. The
      type-specific immune response towards HPV virus-like particles, in combination
      with geographical variation in the prevalence of HPV, necessitates the presence
      of multiple HPV type antigens in a single vaccine cocktail in order to provide
      relevant protection. We aimed to investigate whether co-infection with HIV, which
      is highly prevalent in Africa, plays a role in HPV genotype distribution. After
      informed consent, HPV detection by GP5+/6+ PCR and HIV detection by serology was
      carried out on 236 women from the rural north-western part of Zimbabwe. The
      prevalence of HPV was higher in HIV positive women (54%) than in HIV negative
      women (27%). Certain HPV types (HPV types 11, 39, 43, 51, and 59, P-values
      ranging from 0.017 to 0.067) occurred more frequently in HIV positive women. Only
      high-risk HPV, and not HIV, was associated significantly with cervical
      intraepithelial neoplasia in multiple regression analysis. In conclusion, a high
      prevalence of HPV was found in a rural community, where regular Papanicolaou
      (Pap) smears would be a logistic and economic impossibility, but where free
      vaccination programmes against other infections are already established. The
      results suggest that HIV co-infection may have an impact on HPV genotype
      distribution.

PMID- 15170647
TI  - Human metapneumovirus infection in hospital referred South African children.
AB  - Human metapneumovirus (hMPV) was first described in Dutch children with acute
      respiratory symptoms. A prospective analysis of the epidemiology, clinical
      manifestation, and seroprevalence of hMPV and other respiratory viruses in South
      African children referred to hospital for upper or lower respiratory tract
      infection were carried out during a single winter season, by using RT-PCR, viral
      culture, and enzyme-linked immunosorbent assays. In nasopharyngeal aspirates from
      137 children, hMPV was detected by RT-PCR in 8 (5.8%) children (2-43 months of
      age) as a sole viral pathogen, respiratory syncytial virus (RSV) in 21 (15%),
      influenza A virus in 18 (13%) and influenza B virus in 20 (15%). Pneumonia was
      diagnosed in seven children and upper respiratory tract infection in one of the
      hMPV-infected children. One hMPV-infected child was admitted to the intensive
      care unit in need of mechanical ventilation and one child was infected with human
      immunodeficiency virus (HIV). No statistically significant differences were found
      between hMPV, RSV, and influenza virus infected groups with regard to clinical
      signs and symptoms and chest radiograph findings. The seropositive rate of hMPV
      specific IgG antibodies was 92% in children aged 24-36 months, the oldest
      seronegative child in our study was 7 years and 6 months of age. In conclusion,
      hMPV contributes to upper and lower respiratory tract morbidity in South African
      children.

PMID- 15170648
TI  - Total mesorectal excision for middle and lower rectal cancer: a single
      institution experience with 337 consecutive patients.
AB  - BACKGROUND AND OBJECTIVES: There have been reports on improved prognosis after
      TME for middle and lower rectal cancer. No prospective randomized studies have
      yet been performed. This is a large single institution series evaluating its own
      results of TME. METHODS: This retrospective study analyses data of 337 patients
      with middle and lower rectal cancer, treated with either curative or palliative
      intention between 1990 and 1998. RESULTS: Of all patients, 212 had lower rectal
      and 125 middle rectal carcinomas. The rate of rectal resections with TME was 96%.
      A total of 223 patients were treated by anterior rectal resection; 92 patients
      had to undergo abdomino-perineal resection. Ten patients were operated by a
      Hartmann resection. Postoperative morbidity was 35% with a leakage rate of 9%.
      Postoperative mortality was 4%. The rate of local recurrence was 8.6%. The 5-year
      survival rate after curative resection was 69.3%. The multivariate analysis
      outlined the tumor stage as independent prognostic factor. CONCLUSIONS: In our
      experience, TME is feasible with acceptable postoperative morbidity and low
      mortality. The local recurrence rate can be decreased to lower than 10%. The
      almost 70% 5-year survival rate indicates a clear benefit for the patients. These
      findings recommend TME as standard procedure for middle and lower rectal cancer.

PMID- 15170649
TI  - Pelvic exenteration and sphincter preservation: an analysis of 96 cases.
AB  - BACKGROUND: Pelvic exenteration (PE) is characterized by its technical complexity
      and morbidity rate. Appropriate patient selection prior to the operation allows
      for more conservative surgeries, preserving sphincters, and continent
      reconstruction of the intestinal and urinary tract, contributing to better
      results. METHODS: Between 1980 and 2000, 96 PE were performed. Factors related to
      sphincter preservation as well as factors associated to prognosis were
      respectively analyzed. RESULTS: Of the 96 PE, at least one sphincter in 36
      patients was preserved (37.5%). In the 1990s, the sphincter preservation rate was
      significantly higher than in the 1980s (47.6 vs. 18.2%) (P = 0.005). More serious
      complications happened in 19.8% of the patients and the post-operative mortality
      rate was 15.6%. The post-operative complication rate was not influenced by
      sphincter preservation (P = 0.276). In nine patients, the resection margins were
      compromised microscopically (R1) and in five patients, there were macroscopically
      compromised (R2). The resection margins were not influenced by the type of
      surgery (P = 0.104), nor by the preservation of sphincters (P = 0.881). Twenty
      three patients experienced relapses, 13 being local, eight distant, and two local
      and distant. Disease free survival at 5 years was 40.5%, and the primary site of
      the tumor was a factor associated to differences in disease free survival (P =
      0.027). Overall 5-year survival was 41.9% and was significantly associated to the
      number of organs compromised (P = 0.040) and sphincter preservation (P = 0.026).
      Patients who were submitted to R0 type resection had a median survival of 40.9
      months, while R1 and R2 type resections had a median 21.2 month survival.
      CONCLUSIONS: The appropriate pre-operative selection of the patient and rigorous
      oncological criteria permit PE to be performed while preserving the sphincters in
      selected cases, without harming survival rates.

PMID- 15170650
TI  - Intraoperative imprint cytology of sentinel nodes in breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Sentinel node (SN) biopsy is a new standard of care
      for axillary node staging in patients with early-stage, clinically node-negative
      breast cancer. A second operation can be avoided when the results are available
      intraoperatively. However, there is no standard intraoperative method for SN
      assessment. The aim of this study was to evaluate intraoperative imprint cytology
      (IC) for the detection of SN involvement in patients with early-stage breast
      cancer. METHODS: One hundred eighty-five consecutive patients with a breast tumor
      underwent SN biopsy with intraoperative IC. The SN was bisected and a touch
      preparation was made with a glass slide, on both sides of the cut. Permanent
      sections were evaluated with H&E and immunohistochemical staining. The IC results
      were compared with the final histologic results. RESULTS: The sensitivity,
      specificity, accuracy, and positive and negative predictive values of IC were
      33.3, 78.4, 78.9, 90, and 77.5%, respectively. IC was more sensitive for
      macrometastases than for micrometastases. In the 118 patients studied after the
      learning phase, 9 patients with a positive SN by IC avoided a second operation.
      CONCLUSIONS: Intraoperative IC of SNs appears to be reasonably reliable in
      patients with breast cancer, permitting axillary dissection during the same
      surgical procedure when positive. In contrast, sensitivity for detection of
      micrometastases is low.

PMID- 15170652
TI  - Improving the physical status and quality of life of women treated for breast
      cancer: a pilot study of a structured exercise intervention.
AB  - BACKGROUND AND OBJECTIVES: This pilot project assessed the acceptability of a
      mixed-type, moderate-intensity exercise programme following breast cancer
      treatment, and the impact on presence of lymphoedema, fitness, body composition,
      fatigue, mood and quality of life. METHODS: Ten women completed the programme and
      measures of fitness (sub-maximal ergometer test), body composition (bio
      electrical impedance), lympoedema (bio-electrical impedance and arm
      circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety
      and Depression Scale), quality of life (FACT-B) and general well-being, at
      baseline, completion of the programme, and 6-week and 3-month follow-up. RESULTS:
      Participation in the programme caused no adverse effect on the presence of
      lymphoedema. There was a trend towards reduction in fatigue and improved quality
      of life across the testing phases. Women rated the programme extremely
      favourably, citing benefits of the support of other women, trained guidance, and
      the opportunity to experience different types of exercise. CONCLUSIONS: A mixed
      type, moderate-intensity exercise program in a group format is acceptable to
      women following breast cancer treatment, with the potential to reduce fatigue and
      improve quality of life, without exacerbating or precipitating lymphoedema. This
      pilot work needs to be confirmed in larger randomised studies.

PMID- 15170651
TI  - Positive margins following surgical resection of breast carcinoma: analysis of
      pathologic correlates.
AB  - BACKGROUND AND OBJECTIVES: Histologic margin positivity represents a significant
      source of adverse clinical outcome affecting breast conservation therapy for in
      situ or invasive malignancy. Elucidation of factors associated with positive
      margin status might clarify and improve local therapy strategies. In order to
      define our experience with margin positivity and to identify relevant pathologic
      criteria, we retrospectively analyzed the cases of 143 patients who underwent
      resections for carcinoma with intent of breast conservation between 1995 and
      1999. METHODS: Histologic features and indices of biologic aggressiveness were
      compared among tumors resected with positive versus negative margins in order to
      determine whether such markers could be used to anticipate outcome. RESULTS:
      Twenty-eight pathologic specimens were identified to possess histologically
      positive margins. Twenty-six patients underwent additional operative procedures.
      Of the 26 re-excision specimens, 17 (65%) contained residual malignancy.
      Statistical analysis demonstrated that margin positivity correlated with in situ
      histology and with Her 2/neu positivity. CONCLUSIONS: These data suggest certain
      pathologic factors that may portend difficulty in achieving negative resection
      margins in patients in whom breast conservation therapy is considered.

PMID- 15170653
TI  - Groin soft tissue tumors--a challenge for local control and reconstruction: a
      prospective cohort analysis.
AB  - BACKGROUND AND OBJECTIVES: Groin soft tissue tumors are associated with high
      local recurrence rates of 16-48% and postoperative complications in 40-68%.
      Neoadjuvant chemoradiation and aggressive reconstructive techniques were utilized
      to improve local control and complication rates in this challenging area.
      METHODS: Nine patients in this prospective series were treated with neoadjuvant
      chemoradiation (30 mg IV doxorubicin x 3d followed by 300 cGy/d x 10d) followed
      by surgery and two patients received radiation (5,000 cGy with tissue spacer)
      followed by surgery for tumors with a pelvic/retroperitoneal component. Surgery
      included resection plus reconstruction of the abdominal wall, myocutaneous flaps
      for large defects, and vascular reconstruction as necessary. RESULTS: The 11
      consecutive patients presented with Stage I (30%), II (40%), or III (30%)
      disease. Four patients (36%) were operated on for possible incarcerated hernia
      prior to referral and two (18%) presented with recurrent tumors. Pathology
      included 10 sarcomas and 1 desmoid tumor; tumor grade was low (30%), moderate
      (40%), or high (30%). Local control (mean follow-up 55 months; minimum follow-up
      36 months) and limb salvage rate was 100%. Minor wound complications not
      requiring re-operation occurred in three patients, lymphedema in two, and there
      were no postoperative hernias. CONCLUSIONS: Preoperative therapy provides
      excellent local control of groin soft tissue tumors. Current surgical techniques
      allow extensive resection with limb salvage, dependable primary wound healing and
      long-term integrity of the abdominal wall.

PMID- 15170654
TI  - Margins in extra-abdominal desmoid tumors: a comparative analysis.
AB  - BACKGROUND AND OBJECTIVES: The main treatment of extra-abdominal desmoid tumors
      remains surgery, but recurrence rates up to 80% are reported. The impact of
      microscopic surgical margin status according to the Enneking classification
      system is discussed controversially. METHODS: Therefore, the authors screened the
      published literature for reliable data on the importance of a wide or radical
      excision of extra-abdominal desmoid tumors. All studies with more than ten
      patients, a surgical treatment only, and margin status stated were included.
      RESULTS: Only 12 out of 49 identified studies fulfilled the inclusion criteria.
      One hundred fifty-two primary tumors were excised with wide or radical
      microscopic surgical margins, while in 260 cases a marginal or intralesional
      excision was performed. In the first group 41 patients (27%) and in the second
      one 187 patients (72%) developed a recurrence. Therefore, microscopic surgical
      margin status according to the Enneking classification system is a significant
      prognostic factor (P < 0.001). CONCLUSIONS: The data of this review underline the
      strategy of a wide or radical local excision as the treatment of choice.
      Furthermore, as a large number of studies had to be excluded from this analysis,
      exact microscopic surgical margin status should be provided in future studies in
      order to allow comparability. .

PMID- 15170655
TI  - Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas
      with high and low levels of exposure to aflatoxin B1.
AB  - BACKGROUND AND OBJECTIVES: Previous studies showed that the frequency of beta
      catenin mutation was different in mice when induced by different chemicals. The
      aim of this study is to compare the expression of beta-catenin and p53 in
      hepatocellular carcinoma (HCC) from areas with exposure to high and low levels of
      aflatoxin B1 (AFB1). METHODS: Thirty-five and twenty HCC samples from Guangxi and
      Malaysia, respectively, were studied. The expression of beta-catenin and p53 was
      determined by immunohistochemistry. RESULTS: The overexpression of beta-catenin
      was detected in 65.7% of HCC tissues and 37.1% in adjacent liver tissues samples
      from Guangxi, China. Similarly, overexpression of beta-catenin was also detected
      in 60.0% of HCC tissues and in 35.0% of adjacent liver tissues samples from
      Malaysia. The overexpression of p53 was detected in 42.9% of HCC specimens from
      Guangxi and in 25.0% of HCC specimens from Malaysia. There was a relationship
      between the expression of beta-catenin and hepatitis B virus (HBV) infection in
      the adjacent liver tissues in Guangxi, and between the expression of beta-catenin
      and p53 in HCC tissues in Malaysia. CONCLUSIONS: The differences in the exposure
      to AFB1 did not affect the overexpression of beta-catenin in the development of
      HBV-associated HCC.

PMID- 15170656
TI  - Tumor localization using laparoscopic ultrasound for a small submucosal tumor.

PMID- 15170657
TI  - Contralateral axillary sentinel lymph node drainage in breast cancer: a case
      report.
AB  - BACKGROUND: Since the introduction of sentinel node (SN) mapping in breast
      cancer, extra-axillary lymph node sites of breast tumor drainage are discovered
      in about one-quarter of cases, especially after intraparenchymal injection. In
      most such cases, an ipsilateral axillary SN is associated with an extra-axillary
      SN. Non visualization of ipsilateral axillary SN and extra-axillary SN drainage
      are often associated with an increased risk of axillary involvement. CASE: We
      report a case of contralateral axillary SN drainage on lymphoscintigraphy in a
      breast cancer patient with a history of bilateral reduction mammoplasty and no
      ipsilateral axillary lymph node involvement.

PMID- 15170658
TI  - Evaluation of mRNA expression of estrogen receptor beta and its isoforms in human
      normal and neoplastic endometrium.
AB  - Endometrial cancer is well known to be estrogen-dependent. Two estrogen receptor
      types, ERalpha and ERbeta, are major mediators of a diversity of biologic
      functions of estrogen and play an important role in estrogen-dependent tissues
      and cancers. Cloning of ERbeta was followed by the discovery of a variety of its
      isoforms. Using real-time RT-PCR, the relative expression levels of ERbeta1,
      ERbeta2 (ERbetacx), ERbeta3, ERbeta4 and ERbeta5 were studied. We observed
      coexpression of ERbeta isoforms in the endometrium and upregulation of the
      ERbeta5 transcript in malignant endometrium. We also observed downregulation of
      ERbeta2Delta5 transcript in neoplastic endometrium, using a semiquantitative
      method. Our results suggest that analyzing the changes in ERbeta and its isoforms
      may be important in the diagnosis, prognosis and treatment of endometrial cancer.

PMID- 15170659
TI  - Monolayer versus aggregate balance in survival process for EGF-induced apoptosis
      in A431 carcinoma cells: Implication of ROS-P38 MAPK-integrin alpha2beta1
      pathway.
AB  - A431 cells escape EGF-induced apoptosis by forming cell aggregates. We show that
      these clusters migrate and merge with neighboring ones, resulting in larger
      structures composed of a multilayer central (3D) population surrounded by a cell
      monolayer (2D). We found that after 48 hr of 10 nM EGF treatment, 3D structure
      formation correlates with alpha2beta1 integrin upregulation. Blockade of alpha2
      integrin impairs 3D structure formation. We studied the involvement of reactive
      oxygen species (ROS) in this process. We show that A431 cells express the NADPH
      oxidase catalytic subunits Nox1. EGF-induced dose-dependent ROS production was
      inhibited by the NADPH oxidase inhibitor, diphenylene iodonium (DPI), in these
      cells while rotenone was ineffective. Inhibition of ROS level in A431 cells with
      DPI or ebselen (glutathione peroxydase mimic) as well as P38 MAP kinase
      inhibition by SB203580 decreases alpha2 integrin subunit expression and induces a
      shift to 3D versus 2D populations. Cell cycle analysis of 2D cells shows that
      DPI, ebselen and SB203580 decrease the number of cells in S/G2 phase without
      affecting the cell number in mitosis phase. On the contrary, for 3D cells, these
      treatments increased the proportion of cells in mitosis without modification of
      the cell number in S/G2 phase. For both populations, apoptosis was increased by
      DPI and ebselen. Resistance of cell aggregates by paclitaxel to cell death is
      usually described. We show that DPI abolishes paclitaxel resistance of 3D cell
      aggregates. We observed a greater than additive effect between paclitaxel and DPI
      resulting in an increased proportion of cells in S/G2 phase for 3D populations.
      These results suggested that the ROS-P38 MAP kinase-alpha2beta1 integrin pathway
      was implicated in the A431 survival process by modulating the balance between
      2D/3D cells.

PMID- 15170661
TI  - Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial
      cells in vitro.
AB  - Malignant gliomas are angiogenesis dependent and present a remarkable degree of
      resistance to radiotherapy. In the present work, we studied the effect of
      irradiation of C6 glioma cells on their proliferation and activation in vitro and
      on glioma cell-induced angiogenesis in vivo and in vitro. Irradiation of C6
      glioma cells decreased cell proliferation in a dose-dependent manner.
      Interestingly, metalloproteinase-2 and -9 expression and secretion, as well as
      integrin alpha(v) expression, increased with elevated doses of X rays 48 hr after
      irradiation and was mostly evident at the higher doses used. When pre-irradiated
      C6 cells were implanted on nonirradiated chicken embryo chorioallantoic membranes
      (CAMs), there was a significant dose-dependent increase in tumor induced
      angiogenesis, compared to angiogenesis induced by nonirradiated cells. Similar
      results were obtained when C6 cells were irradiated 48 hr after their inoculation
      onto nonirradiated CAMs. In the same line, conditioned medium from irradiated C6
      cells significantly increased endothelial cell proliferation and migration in
      vitro, in a manner dependent on the dose of X rays. These results explain at
      least in part the low effectiveness of radiation therapy of malignant gliomas and
      support the notion that inhibition of angiogenesis in parallel with radiotherapy
      may represent a new therapeutic approach.

PMID- 15170662
TI  - Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel
      synthetic inhibitor of the urokinase-type plasminogen activator system.
AB  - The overall survival rate of patients suffering from carcinomas has remained poor
      and nearly unchanged over the last decades. This is mainly due to the so-called
      minimal residual disease, i.e., remaining tumor cells that overcome surgery
      and/or radiotherapy and are the cause of locoregional and distant metastases. To
      metastasize, tumor cells take advantage of proteases to invade and remodel
      surrounding tissues. Here, we analyzed the efficiency of WX-UK1, a novel 3
      amidinophenylalanine-based inhibitor of the uPA system, at inhibiting the
      invasive capacity of carcinoma cells. First, uPAR expression was characterized in
      different carcinoma cell lines, including SCCHN, breast and cervical carcinoma.
      Thereafter, the invasive potential of these cell lines was determined using
      Matrigel invasion chambers and a spheroid cocultivation model with human
      fibroblasts. uPAR expression levels correlated positively with invasion capacity,
      which could be significantly inhibited by WX-UK1. A decrease of tumor cell
      invasion by up to 50% was achieved in both models with the SCCHN line FaDu and
      the cervical carcinoma line HeLa after treatment with WX-UK1. Thus, our results
      demonstrate the potential of WX-UK1 in vitro as a promising adjuvant
      antimetastatic therapy of carcinomas.

PMID- 15170660
TI  - Progression to androgen-independent LNCaP human prostate tumors: cellular and
      molecular alterations.
AB  - Lethal phenotypes of human prostate cancer are characterized by progression to
      androgen-independence and metastasis. For want of a clinically relevant animal
      model, mechanisms behind this progression remain unclear. Our study used an in
      vivo model of androgen-sensitive LNCaP human prostate cancer cell xenografts in
      male SCID mice to study the cellular and molecular biology of tumor progression.
      Primary tumors were established orthotopically, and the mice were then surgically
      castrated to withdraw androgens. Five generations of androgen-independent tumors
      were developed using castrated host mice. Tumor samples were used to determine
      expressions of cellular and molecular markers. Androgen-independent tumors had
      increased proliferation and decreased apoptosis compared to androgen-sensitive
      tumors, outcomes associated with elevated expression of p53, p21/waf1, bcl-2, bax
      and the bcl-2/bax ratio. Blood vessel growth in androgen-independent tumor was
      associated with increased expression of vascular endothelial growth factor.
      Overexpression of androgen receptor mRNA and reduced expression of androgen
      receptor protein in androgen-independent tumors suggest that the androgen
      receptor signaling pathway may play an important role in the progression of human
      prostate cancer to androgen-independence. The in vivo orthotopic LNCaP tumor
      model described in our study mimics the clinical course of human prostate cancer
      progression. As such, it can be used as a model for defining the molecular
      mechanisms of prostate cancer progression to androgen-independence and for
      evaluating the effect of preventive or therapeutic regimens for androgen
      independent human prostate cancer.

PMID- 15170663
TI  - Reduction of tumor progression and paraneoplastic syndrome development in murine
      lung adenocarcinoma by nonsteroidal antiinflammatory drugs.
AB  - Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar
      to those present in patients with NSCLC. LP07 tumor-bearing mice develop the
      paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These
      symptoms may be partly due to a systemic inflammatory response. Our aim was to
      determine if treatment with NSAIDs would lower tumor and metastasis growth and
      their accompanying syndromes. The nonselective COX inhibitor indomethacin and the
      selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome
      in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of
      leukocytosis and the weight loss associated with LP07 progression. Serum levels
      of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were
      modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction
      in angiogenesis were attained when cells were treated with either indomethacin or
      celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells
      treated with celecoxib. These data suggest that several processes implicated in
      tumor progression can be modulated with NSAID treatment. Improvement in
      performance status through modulation of cachexia may offer a possibility for
      combining anti-inflammatory treatments with more aggressive therapies.

PMID- 15170664
TI  - Hedgehog signalling in colorectal tumour cells: induction of apoptosis with
      cyclopamine treatment.
AB  - Hedgehog (Hh) signalling controls many aspects of development. It also regulates
      cell growth and differentiation in adult tissues and is activated in a number of
      human malignancies. Hh and Wnt signalling frequently act together in controlling
      cell growth and tissue morphogenesis. Despite the fact that the majority of
      colorectal tumours have a constitutively activated canonical Wnt pathway, few
      previous studies have investigated the expression of Hh signalling components in
      colorectal tumours. We describe here epithelial cell lines derived from both
      nonmalignant colorectal adenomas and colorectal adenocarcinomas that express both
      Sonic and Indian Hh. Interestingly, these cells also express the Hh receptor
      Patched and the downstream signalling components Smoothened and Gli1, suggesting
      autocrine Hh signalling in these cells. To test whether autocrine Hh signalling
      contributes to cell survival, we treated colorectal tumour cells with
      cyclopamine, a known inhibitor of Hh signalling. Cyclopamine treatment induced
      apoptosis in both adenoma- and carcinoma-derived cell lines, which could be
      partially rescued by further stimulation of Hh signalling. These data suggest
      that autocrine Hh signalling can increase aberrant cell survival in colorectal
      tumour cells and may be a novel target for colon cancer therapy using drugs such
      as cyclopamine.

PMID- 15170665
TI  - Pretreatment evaluation of combined HIF-1alpha, p53 and p21 expression is a
      useful and sensitive indicator of response to radiation and chemotherapy in
      esophageal cancer.
AB  - Tumor hypoxia has been known to be associated with resistance to radiation and
      chemotherapy (CRT). Hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription
      factor induced by hypoxic condition, plays a major role in the pleiotropic
      response observed under hypoxic conditions. It encodes proteins that play key
      roles in critical development and physiologic processes, including angiogenesis,
      glucose transport and erythropoiesis. On the other hand, cell cycle- and
      apoptosis-control genes p53 and p21 may play major roles in the tumor response to
      cytotoxic agents such as radiation and chemotherapy. Previous reports have
      suggested that the regulation of p53 and p21 is HIF-1-dependent. Our aim was to
      evaluate the expression of the HIF-1alpha, p53 and p21 proteins by
      immunohistochemistry in biopsy specimens of esophageal squamous cell carcinoma,
      which were obtained endoscopically from 65 patients before CRT, and then
      determine whether the levels of expression of these proteins predicted the
      clinical effectiveness of CRT in individual cancers. Also, to assess the
      relationship between expression of these proteins and cell death and cellular
      proliferation activity, we evaluated Ki67 expression and the apoptosis index
      (TUNEL). HIF-1alpha expression in esophageal cancer was significantly and
      negatively related to the response to CRT, independently of p53 and p21
      expression. Interestingly, 44.4% (12/27) of the HIF-1alpha-negative group showed
      a complete response to therapy. There was no significant correlation between the
      expression of HIF-1alpha, p53 and p21 and proliferation and apoptosis. HIF-1alpha
      overexpression may predict resistance to CRT and may be a helpful guide in
      choosing between therapeutic strategies, such as intensive combined modality
      therapy vs. palliative therapy. Combined immunohistochemical evaluation of HIF
      1alpha, p53 and p21 protein expression at the pretreatment biopsy is a very
      useful and powerful indicator of sensitivity to CRT in human esophageal cancer.
      Our data also indicate the importance of having a clear grasp of the degree of
      hypoxia (HIF-1alpha) of a tumor, rather than its cellular character
      (proliferation and apoptosis), to indicate the likely impact of CRT.

PMID- 15170666
TI  - The variant E233G of the RAD51D gene could be a low-penetrance allele in high
      risk breast cancer families without BRCA1/2 mutations.
AB  - Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not
      previously characterized. The novel variant E233G in RAD51D is more highly
      represented in high-risk, site-specific, familial breast cancer cases that are
      not associated with the BRCA1/2 genes, with a frequency of 5.74% (n = 174)
      compared to a control population (n = 567) and another subset of breast cancer
      patients (n = 765) with a prevalence of around 2% only (comparison to controls,
      OR = 2.6, 95% CI 1.12-6.03; p < 0.021). We found that the immunohistochemical
      profile detected in available tumors from these patients differs slightly from
      those described in non-BRCA1/2 tumors. Finally, the structural prediction of the
      putative functional consequence of this change indicates that it can diminish
      protein stability and structure. This suggests a role for E233G as a low
      penetrance susceptibility gene in the specific subgroup of high-risk familial
      breast cancer cases that are not related to BRCA1/2.

PMID- 15170667
TI  - Pathways of urothelial cancer progression suggested by Bayesian network analysis
      of allelotyping data.
AB  - Urothelial cancers of the bladder (UC) comprise biologically heterogeneous group
      of tumors and display complex genetic alterations. Several genetic changes have
      been analyzed in detail and some of them are associated with the development and
      progression of UCs. Only a few studies, however, are focused on identifying the
      order in which the aberrations may appear during UC tumorigenesis. We have
      analyzed 123 papillary UCs of the bladder by microsatellites for each of the
      chromosomal regions that have been suggested to be specifically involved in this
      type of tumor. We used Bayesian network modeling that enables to uncover
      multivariate probabilistic dependencies between variables. This methodology
      applied to LOH data allowed us to discover patterns of losses in UCs. Exploiting
      the mechanism of probabilistic reasoning in Bayesian networks we suggest primary
      and secondary events in tumor pathogenesis and reconstruct the possible flow of
      progression of allelic changes. Losses of chromosome 9p and 9q were found to be
      the primary events. Losses of 8p and 17p are important events leading to
      progression of tumor cell clones. The loss of 17p occurs when both abnormalities
      of chromosome 9 and 8p are already present. There are chromosomal losses related
      to 8p (1q, 18q, 10q) and some losses like 5q/5p were associated with 17p, leading
      to the hypothesis of different genetic pathways of UC progression. The
      abnormalities of chromosome regions 13q, 16q, 6q, 14q, 3p are suggested to be
      late events being accumulated during the progression of cancer. Although some
      genetic changes were associated only with the 8p pathway, most secondary genetic
      changes appear in both pathways. Supplementary material for this article can be
      found on the International Journal of Cancer website at
      http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

PMID- 15170668
TI  - Molecular classification of oral cancer by cDNA microarrays identifies
      overexpressed genes correlated with nodal metastasis.
AB  - Our purpose was to classify OSCCs based on their gene expression profiles, to
      identify differentially expressed genes in these cancers and to correlate genetic
      deregulation with clinical and histopathologic data and patient outcome. After
      conducting proof-of-principle experiments utilizing 6 HNSCC cell lines, the gene
      expression profiles of 20 OSCCs were determined using cDNA microarrays containing
      19,200 sequences and the BTSVQ method of data analysis. We identified 2 sample
      clusters that correlated with the T3-T4 category of disease (p = 0.035) and nodal
      metastasis (p = 0.035). BTSVQ analysis identified a subset of 23 differentially
      expressed genes with the lowest QE scores in the cluster containing more advanced
      stage tumors. Expression of 6 of these differentially expressed genes was
      validated by quantitative real-time RT-PCR. Statistical analysis of quantitative
      real-time RT-PCR data was performed and, after Bonferroni correction, CLDN1
      overexpression was significantly correlated with the cluster containing more
      advanced-stage tumors (p = 0.007). Despite the clinical heterogeneity of OSCC,
      molecular subtyping by cDNA microarray analysis identified distinct patterns of
      gene expression associated with relevant clinical parameters. Application of this
      methodology represents an advance in the classification of oral cavity tumors and
      may ultimately aid in the development of more tailored therapies for oral
      carcinoma.

PMID- 15170669
TI  - Genetic evolution in colon cancer KM12 cells and metastatic derivates.
AB  - So far, CRC cell lines have contributed to descriptions of 2 patterns of genetic
      instability, affecting either microsatellite sequences or chromosome number and
      structure. Often, these patterns are mutually exclusive; while near-diploid
      karyotypes usually appear with MSI and chromosomal stability, near-triploid or
      tetraploid cells display a high degree of CIN and are stable at the
      microsatellite level. In the present study, we describe the genomic instability
      pattern of KM12 CRC cells. KM12C and derived cell lines with different metastatic
      properties were analyzed by conventional cytogenetics, CGH and M-FISH. Results
      were compared to 5 cell lines usually used as model of MSI and CIN. Concordance
      between our results and previously published SKY data are also reviewed.
      Interestingly, the poorly metastatic KM12C cell line displayed a near-diploid
      karyotype with high levels of structural chromosome instability and
      microsatellite instability. The highly metastatic KM12SM and KM12L4A cell lines
      showed polyploid karyotypes and maintained CIN and MSI. A comparison between
      karyotypes of poorly and highly metastatic KM12 cell lines allowed us to
      delineate a cytogenetic evolution pathway. Our results clearly demonstrated that
      endoreduplication was the origin of the polyploid dosages in the highly
      metastatic forms following the monosomic model postulated for CRC. Therefore, we
      demonstrate that KM12C cells and their metastatic derivates, KM12SM and KM12L4A,
      are a useful model of chromosomal evolution where MSI may coexist with CIN.

PMID- 15170670
TI  - Inhibition of a complement regulator in vivo enhances antibody therapy in a model
      of mammary adenocarcinoma.
AB  - Membrane-bound complement regulatory proteins provide tumor cells with protection
      from antibody and complement in vitro. However, complement regulators are widely
      expressed on normal tissue, and inhibiting the function of complement regulatory
      proteins on tumor cells in vivo has not been investigated due to the absence of
      appropriate tumor-targeting strategies. Using a mouse model of rat mammary
      adenocarcinoma, we demonstrate that tumor-specific targeting of a complement
      regulator with a blocking antibody has functional consequences with regard to
      both complement deposition on tumor cells and the efficacy of monoclonal antibody
      therapy. Rat adenocarcinoma 13762 cells express Crry, a widely expressed rodent
      regulator of complement activation, and are recognized by C595 MAb, an anti-MUC1
      MAb in clinical trials. Anti-rat Crry 5I2 MAb and F(ab)(2) enhanced complement
      deposition on C595 MAb-sensitized 13762 cells in vitro. In vivo, C595 MAb bound
      to 13762 tumors, albeit not specifically, but was not therapeutic when
      administered after tumor challenge. However, the coadministration of 5I2 MAb with
      C595 MAb resulted in enhanced complement deposition and significantly delayed
      tumor onset and reduced tumor growth; 5I2 MAb alone also enhanced complement
      deposition and reduced tumor growth but less effectively than when combined with
      C595 MAb; 5I2 MAb alone did not directly activate mouse complement, but its
      inhibitory effect on Crry enhanced complement deposition following complement
      activation by both the alternative pathway and by natural IgM reactive to 13762
      cells present in mouse serum. Our proof of principle study shows that inhibiting
      the function of a tumor-expressed complement regulatory protein enhances immune
      mediated clearance of tumor cells and improves prospects for successful
      immunotherapy. The results justify further research and development of targeting
      strategies to inhibit or downregulate complement regulatory proteins on tumor
      cells.

PMID- 15170671
TI  - Targeting an extracellular epitope of the human multidrug resistance protein 1
      (MRP1) in malignant cells with a novel recombinant single chain Fv antibody.
AB  - Inherent and acquired multidrug resistance (MDR) is characterized by a
      simultaneous resistance to diverse anticancer drugs and is a major impediment
      towards curative chemotherapy of cancer. Hence one important goal is to develop
      strategies aimed at specific targeting of major anticancer drug efflux
      transporters of the ATP-binding cassette (ABC) superfamily including multidrug
      resistance protein 1 -MRP1 (ABCC1). To date, no monoclonal antibody has been
      isolated that can target an extracellular MRP1 epitope. Using a phage display
      approach, we have isolated a recombinant single-chain Fv (scFv) antibody that
      specifically reacts with the extracellular N-terminus of the human MRP1. Flow
      cytometric analysis revealed that this scFv fragment binds specifically to
      various viable human tumor cells that display variable MRP1 expression levels but
      not to MRP1 null cells. Furthermore, this scFv antibody failed to react with
      tumor cells that overexpress other members of the MRP family that have an
      extracellular N-terminus (MRP2 and MRP3) as well as with MRP4, MRP5, and breast
      cancer resistance protein. Flow cytometric analysis also showed a good
      correlation between the fluorescence intensity of the anti-MRP1 scFv antibody and
      MRP1 levels in viable tumor cells. These findings constitute the first successful
      isolation of a small recombinant scFv antibody directed to an extracellular
      epitope of the MRP1 in viable malignant cells. These novel small Fv-based
      recombinant antibodies that possess superior tumor penetration capabilities may
      possibly be used to selectively target drugs or tumor cells that express MRP-1.

PMID- 15170672
TI  - Genetic abnormalities in plasma DNA of patients with lung cancer and other
      respiratory diseases.
AB  - The detection of tumour-associated genetic alterations in plasma DNA has been
      proposed as a simple method for the early diagnosis of lung cancer and for
      identifying individuals at high risk of lung cancer who might be included in
      screening or chemoprevention programmes. To evaluate the practicality of this
      approach, we screened a panel of 16 plasma DNA markers in a lung cancer
      population to identify those with the highest genetic alteration rate. These were
      then used to study plasma DNA in 206 hospital outpatients with lung cancer and
      other respiratory diseases. Plasma and lymphocyte DNA were isolated from blood
      samples collected from hospital outpatients. Polymerase chain reaction was
      carried out with 16 microsatellite markers covering chromosomal regions 3p, 8p,
      9p, 13q and 17p, using DNA from 32 lung cancer patients. The 3 markers most
      commonly affected were selected for use in a larger study of 86 lung cancer
      patients and 120 patients with other respiratory diseases. In the pilot study, 3
      primer pairs (D3S1300, D3S1560, D8S201) together detected genetic alterations in
      plasma DNA in 60% of lung cancer patients. In the larger study, significantly
      higher genetic alteration rates were observed in lung cancer patients than in
      patients with other respiratory diseases for the two markers D3S1560 and D8S201.
      The overall genetic alteration rate was 69% in the lung cancer patients and 42%
      in the patients with other respiratory diseases (p < 0.001). Analysis of plasma
      and lymphocyte DNA to detect genetic alterations typical of lung cancer is
      possible in large studies. The genetic alteration rate we found in lung cancer
      patients was comparable with other studies. Although the genetic alteration rate
      was significantly higher in the lung cancer than the respiratory disease
      patients, it did not have good positive predictive value in this population.
      Longitudinal studies are required to determine whether genetic changes in plasma
      DNA of non-cancer patients indicate a high risk of later lung cancer.

PMID- 15170673
TI  - Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits
      azoxymethane-induced rat colon carcinogenesis through elevation of colonic
      PPARgamma expression and alteration of lipid composition.
AB  - Our previous short-term experiment demonstrated that seed oil from bitter melon
      (Momordica charantia) (BMO), which is rich in cis(c)9, trans(t)11, t13-conjugated
      linolenic acid (CLN), inhibited the development of azoxymethane (AOM)-induced
      colonic aberrant crypt foci (ACF). In our study, the possible inhibitory effect
      of dietary administration of BMO on the development of colonic neoplasms was
      investigated using an animal colon carcinogenesis model initiated with a colon
      carcinogen AOM. Male F344 rats were given subcutaneous injections of AOM (20
      mg/kg body weight) once a week for 2 weeks to induce colon neoplasms. They also
      received diets containing 0.01%, 0.1% or 1% BMO for 32 weeks, starting 1 week
      before the first dosing of AOM. At the termination of the study (32 weeks), AOM
      induced 83% incidence (15/18 rats) of colonic adenocarcinoma. Dietary
      supplementation with 0.01% and 0.1% BMO caused significant reduction in the
      incidence (47% inhibition by 0.01% BMO, p<0.02; 40% inhibition by 0.1% BMO,
      p<0.05; and 17% inhibition by 1% BMO) and the multiplicity (64% inhibition by
      0.01% BMO, p<0.005; 58% inhibition by 0.1% BMO, p<0.02; and 48% inhibition by 1%
      BMO, p<0.05) of colonic adenocarcinoma, though a clear dose response was not
      observed. Such inhibition was associated with the increased content of CLA
      (c9,t11-18:2) in the lipid composition in colonic mucosa and liver. Also, BMO
      administration in diet enhanced expression of peroxisome proliferator-activated
      receptor (PPAR) gamma protein in the nonlesional colonic mucosa. These findings
      suggest that BMO rich in CLN can suppress AOM-induced colon carcinogenesis and
      the inhibition might be caused, in part, by modification of lipid composition in
      the colon and liver and/or increased expression of PPARgamma protein level in the
      colon mucosa.

PMID- 15170675
TI  - Accuracy of visual screening for cervical neoplasia: Results from an IARC
      multicentre study in India and Africa.
AB  - Visual inspection-based screening tests, such as visual inspection with 4% acetic
      acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to
      cytology in mass screening programs. To date, there is only limited information
      on the accuracy of these tests in detecting High-grade Squamous Intraepithelial
      Lesions (HSIL). Eleven cross-sectional studies involving 56,939 women aged 25-65
      years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to
      evaluate the accuracy of VIA and VILI performed by health workers. A common
      protocol and questionnaire was used. For final diagnosis, all women were
      investigated with colposcopy and biopsies were taken when necessary. Data from
      the studies were pooled to calculate sensitivity, specificity and predictive
      values of the tests for the detection of HSIL. Of the screened women, 16.1% and
      16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were
      diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative
      predictive values for VIA were 76.8% (95% CI: 74.2-79.4%), 85.5% (95% CI: 85.2
      85.8%), 9.4% (95% CI:8.8-10.8%) and 99.5% (95% CI:99.4-99.6%), respectively. The
      values were 91.7% (95% CI: 89.7-93.4%), 85.4% (95% CI: 85.1-85.7%), 10.9% (95%
      CI: 10.2-11.6%) and 99.8% (95% CI:99.7-99.9%), respectively for VILI. The range
      of sensitivity and specificity for VIA was 56.1-93.9% and 74.2-93.8%,
      respectively, between studies and were 76.0-97.0 % and 73.0-91.3% for VILI. VILI
      had a significantly higher sensitivity than VIA in detecting HSIL, but
      specificity was similar. VILI appears to be a more accurate visual test for use
      in screening and treatment programs in low-resource settings.

PMID- 15170674
TI  - Prevalence of familial pancreatic cancer in Germany.
AB  - Based on several case-control studies, it has been estimated that familial
      aggregation and genetic susceptibility play a role in up to 10% of patients with
      pancreatic cancer, although conclusive epidemiologic data are still lacking.
      Therefore, we evaluated the prevalence of familial pancreatic cancer and
      differences to its sporadic form in a prospective multicenter trial. A total of
      479 consecutive patients with newly diagnosed, histologically confirmed
      adenocarcinoma of the pancreas were prospectively evaluated regarding medical and
      family history, treatment and pathology of the tumour. A family history for
      pancreatic cancer was confirmed whenever possible by reviewing the tumour
      specimens and medical reports. Statistical analysis was performed by calculating
      odds ratios, regression analysis with a logit-model and the Kaplan-Meier method.
      Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least
      1 first-degree relative with pancreatic cancer. The familial aggregation could be
      confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical
      records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews
      of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6),
      respectively. There were no statistical significant differences between familial
      and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence
      of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis
      after palliative or curative treatment as well as associated tumours in index
      patients and families, respectively. The prevalence of familial pancreatic cancer
      in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation
      of the pancreatic carcinoma in relatives. This prevalence is lower than so far
      postulated in the literature. There were no significant clinical differences
      between the familial and sporadic form of pancreatic cancer.

PMID- 15170676
TI  - Evaluation of circulating thyroid-specific transcripts as markers of thyroid
      cancer relapse.
AB  - Circulating thyroid-specific transcripts have been suggested as potential
      molecular markers of residual or recurrent thyroid cancer. We assessed the
      accuracy of real-time RT-PCR-based detection of a panel of thyroid-specific
      markers, including TG, TPO, TSHR, NIS and PDS, in comparison with serum TG
      measurements in a series of 55 patients operated for differentiated thyroid
      cancer (DTC). Serum TG levels were higher in patients with residual thyroid
      tissue or metastatic cancer than in disease-free patients during thyroid hormone
      suppressive therapy (THST) and after stimulation with rhTSH (P < 0.05).
      Recombinant hTSH increased serum TG values in patients with tumor relapse (P <
      0.05), but not in disease-free patients. This assay showed high specificity and
      good sensitivity in detecting tumor relapse (accuracy under THST = 81.4%; after
      rhTSH stimulation = 90.9%). TPO and TSHR mRNA, either under THST or after rhTSH,
      showed a significant correlation with disease status for molecular assays.
      Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high
      sensitivity but low specificity in the prediction of thyroid cancer recurrence or
      metastases (accuracy under THST = 51%, 43% and 54%, respectively), whereas TPO
      and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy
      under THST of 67% and 61%, respectively, that improved when these tests were
      combined. Our findings indicate that serum TG assay after TSH stimulation is the
      most accurate test for monitoring DTC. Combined measurements of TPO and TSHR mRNA
      levels during THST may represent a specific test for early detection of DTC
      relapse.

PMID- 15170677
TI  - Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in
      human tumor cells.
AB  - Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin;
      CPT-11) is a widely used potent antitumor drug that inhibits mammalian DNA
      topoisomerase I (Topo I); however, overexpression of ABCG2 (BCRP/MXR/ABCP) can
      confer cancer cell resistance to SN-38, the active form of CPT-11. We have
      recently demonstrated that plasma membrane vesicles prepared from ABCG2
      overexpressing PC-6/SN2-5H cells transported SN-38 and its glucuronide conjugate
      in an ATP-dependent manner (Nakatomi et al., Biochem Biophys Res Commun
      2001;288:827-32). In the present study, we have characterized a total of 14 new
      camptothecin (CPT) analogues with respect to both the inhibition of Topo I and
      the substrate specificity of ABCG2. All of the tested CPT analogues, which have
      different substitutions at positions 10 and 11, strongly inhibited the Topo I
      activity in a cell-free system, as did SN-38. Their antitumor activities in the
      SN-38-resistant PC-6/SN2-5H2 cell line greatly varied, however, being correlated
      with intracellular accumulation levels. We have examined ATP-dependent transport
      of those CPT analogues by using plasma membrane vesicles prepared from both PC
      6/SN2-5H2 cells and ABCG2-transfected HEK-293 cells. Based on the substrate
      specificity of ABCG2 thus evaluated, it is strongly suggested that CPT analogues
      with high polarity are good substrates for ABCG2 and are therefore effectively
      extruded from cancer cells. In this context, to circumvent ABCG2-associated drug
      resistance, low-polarity CPT analogues are considered to be potent lead
      compounds. The present study provides a practical approach to discover new CPT
      based drugs for the chemotherapy of drug-resistant human cancer.

PMID- 15170678
TI  - HPV-18 E6*I modulates HPV-18 full-length E6 functions in a cell cycle dependent
      manner.
AB  - The E6 ORFs of the high-risk Human Papillomavirus (HPV) Types 16 and 18 have been
      shown to encode (besides the full-length product) several truncated forms, termed
      E6*. We have reported previously that the HPV-18 E6*I protein interacts with the
      full-length E6 protein as well as with the ubiquitin ligase E6-AP and, as a
      result of this, E6* can inhibit E6-mediated degradation of p53. Moreover, ectopic
      expression of the HPV-18 E6*I protein has an antiproliferative effect in cervical
      cancer-derived cell lines. These results led us to investigate further the
      modulatory functions of E6*I on E6. Using epitope tagged versions of the 2
      proteins we have analyzed the sub-cellular distribution of the full-length HPV18
      E6 and HPV18 E6*I, as well as their respective cellular abundance during the cell
      cycle, and show specific upregulation of E6*I during G2/M. We also investigated
      the effect of E6*I overexpression in cell lines derived from cervical tumors,
      with respect to the expression levels of E6 target proteins, such as p53, hDlg
      and Scribble and find a corresponding increase in p53 expression also during
      G2/M. In addition we show that the overexpression of E6*I reduces the amount of
      E6 in the insoluble nuclear and membrane fractions of the cell. E6 levels can,
      however, be restored by the addition of a specific proteasome inhibitor,
      suggesting that the interaction between E6 and E6*I leads to the destabilization
      of a subset of the E6 protein. These results suggest that the E6*I protein can
      function as a fine regulator of the full-length E6 protein by direct interaction
      that leads both to changes in its cellular abundance as well as its distribution
      during particular phases of the cell cycle.

PMID- 15170682
TI  - New eyes for old bones: The power of virtual study of the fossil hominid from
      Eliye Springs, Kenya, by CT-based 3D reconstruction.

PMID- 15170684
TI  - 2004 Henry Gray Award.

PMID- 15170685
TI  - A.J. Ladman AAA/Wiley Exemplary Service Award.

PMID- 15170686
TI  - Nervus terminalis derived from the neural crest? A surprising new turn in a
      century-old debate.

PMID- 15170687
TI  - Increasing active student participation in histology.
AB  - As have many institutions, the New York University School of Medicine (NYUSM) has
      instituted curriculum revisions that allow for increased independent study but
      impose significant time constraints on laboratory courses. Challenged by
      decreased laboratory time, we sought creative solutions for our histology course,
      "Cell Biology of Tissues and Organs," using computer- and Web-based materials.
      While these solutions have facilitated independent study, they have not fostered
      the subtler lessons learned in the laboratory, such as communication skills and
      team approaches to learning. To retain these elements and enrich our course, we
      focused on increasing student participation in the laboratory through unit
      reviews presented by students, student-generated comprehensive reviews, and
      practice exams. The active engagement of students in the learning process has
      resulted in a more exciting laboratory experience for all.

PMID- 15170688
TI  - Traditional teaching supported by computer-assisted learning for macroscopic
      anatomy.
AB  - Over the years we have observed that there is a very low passing rate for the
      Anatomy and Neuroanatomy courses in our department, and for that reason we
      decided to implement the use of student-learning resources. The objective of this
      study was to compare the results of traditional methodology with those obtained
      with the support of computer-assisted learning (CAL). We performed a
      retrospective and joint study for Anatomy and Neuroanatomy groups during the
      period of September 2001 to February 2003, to establish a comparison between
      traditional learning and traditional learning supported by CAL. In the Anatomy
      group, students who used the traditional method (n1 = 365) received an average
      final grade of 58 (SD = 14.94), while the average final grade for students who
      used the traditional method supported by CAL (n2 = 283) was 68 (SD = 14.56). In
      the Neuroanatomy group, the students who used the traditional method (n3 = 217)
      had an average final grade of 61 (SD = 14.51), while the students who used the
      traditional method supported by CAL (n4 = 134) received an average final grade of
      68 (SD = 13.52). A z-test was conducted to determine the difference in averages
      between the two groups (alpha = 0.05), and the results showed that the averages
      were significantly different (P <.001). The modified traditional method with CAL
      support was shown to be the best option in comparison with the traditional
      method.

PMID- 15170689
TI  - Race: scientific nonproblem, cultural quagmire.
AB  - The matter of biological differentiation among human beings has been a perennial
      concern of physical anthropologists, whose profession grew out of the
      monogenist/polygenist debates of the 18th century, and who periodically feel
      impelled to issue sonorous pronouncements on the subject. In spite of (or perhaps
      because of) the extensive and difficult cultural ramifications of the race issue,
      such pronouncements have usually presented the matter of race as one that
      requires extensive bioanthropological exegesis. In reality, however, race is the
      most banal of biological issues. Within any species, including Homo sapiens, two
      biological processes are possible: physical differentiation (as routinely occurs
      in small population isolates) and reintegration (should the resulting
      differentiated populations come together in the absence of any barrier to
      mating). The history of Homo sapiens reflects both of these processes: initial
      differentiation among small, scattered populations in the later part of the
      Pleistocene, and subsequent reintegration as the human population expanded and
      these populations came together once more. It is for this reason that, while
      certain modal physical types can be recognized on any urban street today
      (differentiation), it is impossible to recognize any clear boundaries between
      them (reintegration). All of this is perfectly unremarkable in evolutionary
      terms, and requires no special explanation. The complexities of the race issue
      are real, of course, and it is important that we come to terms with them; but
      they will not be resolved by biologists.

PMID- 15170690
TI  - Acridine orange staining method to reveal the characteristic features of an
      intravascular threadlike structure.
AB  - A threadlike structure in blood vessels that is considered part of the Bohghan
      duct system was first reported about 40 years ago. This structure has remained
      elusive since then due to the inability of other researchers to duplicate the
      original identification. In this study we identified the characteristic features
      of this threadlike structure in rats by the use of fluorescent microscope imaging
      of nuclei stained by acridine orange perfusion. The nuclei of the tissue that
      comprises the structure are rod-shaped, 10-20 microm long, and aligned in a
      broken-line striped fashion. The novel technique reported here can differentiate
      the intravascular threadlike structure from the fibrin strings that normally form
      during perfusion and can confound the observation procedure. The physiological
      function of the threadlike structure remains to be elucidated; however, further
      study may provide a new understanding of mammalian biology in general, and of
      acupuncture and Oriental medicine in particular.

PMID- 15170691
TI  - Plasmid-based short-hairpin RNA interference in the chicken embryo.
AB  - The chicken neural tube serves as an ideal model for new techniques to alter gene
      expression. We show that short-hairpin RNA delivered by a plasmid vector can
      effectively knock down expression of both exogenous and endogenous genes in the
      chicken neural tube. We also assay the effects of short-hairpin RNA on the
      interferon response and find no difference between electroporation of a control
      plasmid and a short-hairpin RNA plasmid.

PMID- 15170692
TI  - Tissue-specific distribution of donor mitochondrial DNA in cloned mice produced
      by somatic cell nuclear transfer.
AB  - Highly diverse results have been reported for mitochondrial DNA (mtDNA) hetero
      plasmy in nuclear-transferred farm animals. In this study, we cloned genetically
      defined mice and investigated donor mtDNA inheritance following somatic cell
      cloning. Polymerase chain reaction (PCR) analysis with primers that were specific
      for either the recipient oocytes or donor cells revealed that the donor mtDNA
      coexisted with the recipient mtDNA in the brain, liver, kidney, and tail tissues
      of 96% (24/25) of the adult clones. When the proportion of donor mtDNA in each
      tissue was measured by allele-specific quantitative PCR and subjected to ANOVA
      analysis, a tissue-specific mtDNA segregation pattern (P < 0.05) was observed,
      with the liver containing the highest proportion of donor mtDNA. Therefore, the
      donor mtDNA was inherited consistently by the cloned offspring, whereas donor
      mtDNA segregation was not neutral, which is in accordance with previous notions
      about tissue-specific nuclear control of mtDNA segregation.

PMID- 15170693
TI  - Ectopic activation of Dpp signalling in the male Drosophila germline inhibits
      germ cell differentiation.
AB  - The mechanisms that control differentiation of stem cells to specialised cell
      types probably include factors intrinsic to stem cells as well as extrinsic
      factors produced by the microenvironment of the stem cell niche. The Drosophila
      male germline is renewed from a population of stem cells located in the apical
      tip of the adult testis. The morphological relationship between germline stem
      cells and their surrounding somatic cells is well understood but the factors that
      regulate stem cell proliferation and differentiation are still being uncovered.
      This study examined the effect of stimulating Dpp signalling directly in male
      germ cells. Ectopic Dpp or Activin signalling resulted in overproliferation of
      both stem cell-like and spermatogonial-like cells in the apical region of the
      testis. A third cell population that expressed stem cell markers was seen to
      proliferate in the distal testis when Dpp signalling was either stimulated or
      repressed in germline stem cells.

PMID- 15170694
TI  - Lentivirally generated eGFP-transgenic rats allow efficient cell tracking in
      vivo.
AB  - Here we describe the efficient generation of eGFP-transgenic rats using a
      lentiviral approach. Analysis of the founder generation demonstrated that 46% of
      the offspring had stably integrated the provirus into the genome and of those 92%
      expressed eGFP in all blood-derived leukocytes. In contrast to their offspring,
      all founder rats were mosaic with regard to eGFP-expression, suggesting delayed
      viral transduction after injection. The expression level of eGFP in the F1
      generation is influenced by and segregates with the site of proviral integration.
      Interestingly, a single copy of the transgene is sufficient for reliable
      detection by flow cytometry, irrespective of the leukocyte subtype analyzed.
      Adoptive transfer of purified CD4(+) T-lymphocytes from transgenic rats and
      subsequent reisolation from various organs further demonstrated that expression
      of the lentiviral transgene is maintained in a foreign host and therefore allows
      for efficient tracking of transferred cells. Taken together, lentivirally
      generated eGFP-transgenic rats are a powerful tool for various applications in
      immunology and presumably also many other fields.

PMID- 15170695
TI  - Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum
      free media.
AB  - C57BL/6 is a well-characterized mouse strain that is used extensively for
      immunological and neurological research. The establishment of C57BL/6 ES cell
      lines has facilitated the study of gene-altered mice in a pure genetic background
      however, relatively few such lines exist. Using a defined media supplement,
      knockout serum replacement (KSR) with knockout DMEM (KSR-KDMEM), we find that we
      can readily establish ES cell lines from blastocysts of C57BL/6J mice. Six lines
      were established, all of which were karyotypically normal and could be maintained
      in the undifferentiated state on mouse embryonic fibroblast (MEF) feeders. One
      line was further tested and found to be karyotypically stable and germline
      competent, both prior to manipulation and after gene targeting. For this cell
      line, efficiencies of cell cloning and chimera generation were greater when
      maintained in KSR-KDMEM. Our work suggests that the use of defined serum-free
      media may facilitate the generation of ES cells from inbred mouse strains.

PMID- 15170696
TI  - Neurogenic phenotypes induced by RNA interference with bHLH genes of the Enhancer
      of split complex of Drosophila melanogaster.
AB  - The Enhancer of split gene complex [E(spl)-C] of Drosophila melanogaster harbors
      seven highly related genes encoding transcriptional regulators with a basic helix
      loop-helix (bHLH) domain. They are activated by the Notch signaling pathway in
      order to inhibit proneural gene activity, for example, during neurogenesis in the
      developing embryo. The E(spl) proteins are at least partly redundant, despite
      some remarkable differences in their expression patterns. We attempted to address
      the degree of redundancy by means of RNA interference. We find a quantitative
      correlation between the degree of a neurogenic phenotype and the number of genes
      affected. Surprisingly, interference with m3 results in a high rate of mortality
      which cannot be reproduced by genetic mutation. Most likely, m3 dsRNA interferes
      with unrelated genes involved in other aspects of embryonic development.

PMID- 15170697
TI  - Dll3 pudgy mutation differentially disrupts dynamic expression of somite genes.
AB  - Mutations in the notch ligand delta-like 3 have been identified in both the pudgy
      mouse (Dll3(pu); Kusumi et al.: Nat Genet 19:274-278, 1998) and the human
      disorder spondylocostal dysostosis (SCD; Bulman et al.: Nat Genet 24:438-441,
      2000), and a targeted mutation has been generated (Dll3(neo); Dunwoodie et al.:
      Development 129:1795-1806, 2002). Vertebral and rib malformations deriving from
      defects in somitic patterning are key features of these disorders. In the mouse,
      notch pathway genes such as Lfng, Hes1, Hes7, and Hey2 display dynamic patterns
      of expression in paraxial mesoderm, cycling in synchrony with somite formation
      (Aulehla and Johnson: Dev Biol 207:49-61, 1999; Forsberg et al.: Curr Biol 8:1027
      1030, 1998; Jouve et al.: Development 127:1421-1429, 2000; McGrew et al.: Curr
      Biol 8:979-982, 1998; Nakagawa et al.: Dev Biol 216:72-84, 1999). We report here
      that the Dll3(pu) mutation has different effects on the expression of cycling
      (Lfng and Hes7) and stage-specific genes (Hey3 and Mesp2). This suggests a more
      complex situation than a single oscillatory mechanism in somitogenesis and
      provides an explanation for the unique radiological features of the human DLL3
      type of SCD.

PMID- 15170698
TI  - Coat color-tagged green mouse with EGFP expressed from the RNA polymerase II
      promoter.
AB  - Laborious molecular genotyping and variegated gene expression are two widely
      encountered issues for transgenic mouse studies. To facilitate genotyping in the
      FVB/N albino background and to reduce variegated expression, we successfully
      generated double-tagged transgenic mice for direct visual genotyping with the
      coat color phenotype derived from tyrosinase cDNA driven by the tyrosinase
      promoter and with simultaneous high enhanced green fluorescent protein (EGFP)
      expression driven by the promoter of RNA polymerase II large subunit gene.
      Incorporation of insulator into a transgene construct achieved high efficiency of
      transgene expression in more than 90% of the founders. EGFP was detected as early
      as the one-cell fertilized egg and lasted for the whole embryo development, as
      well as in all of the adult tissues examined. The coat color-tagged green mice
      offer opportunities in applications such as tissue transplantation, lineage
      tracing, chimera biology, RNA interference, and other transgenic studies.

PMID- 15170699
TI  - Identification of neuron-specific promoters in Ciona intestinalis.
AB  - We isolated 5' flanking regions of four genes, Ci-Galphai1, Ci-arr, Ci-vAChTP,
      and Ci-vGAT, each of which is expressed in distinct sets of neurons in the
      central nervous system of the ascidian Ciona intestinalis, and we examined their
      function by introducing green fluorescent protein (GFP)-fusion constructs into
      Ciona embryos. The reporter gene driven by the 5' flanking region of Ci-Galphai1,
      Ci-arr, and Ci-vAChTP recapitulated the endogenous gene expression patterns,
      while that of Ci-vGAT can drive GFP expression in particular subsets of neurons
      expressing the endogenous gene. Deletion analysis revealed that the Ci-Galphai1
      promoter consists of multiple regulatory modules controlling the expression in
      different types of cells. The GFP fluorescence enabled visualization of cell
      bodies and axons of different sets of neurons in ascidian larvae. These promoters
      can be a powerful tool for studying molecular mechanisms of neuronal development
      as well as neuron networks and functions in ascidians.

PMID- 15170700
TI  - Long-range effect of upd, a ligand for Jak/STAT pathway, on cell cycle in
      Drosophila eye development.
AB  - unpaired (upd) encodes a ligand for the Jak/STAT signaling pathway in Drosophila.
      In the second instar and early third larval eye disc, upd is expressed in the
      center of the posterior margin. upd loss-of-function mutations caused eye size
      reduction and upd overexpression caused eye enlargement. Upd regulates eye size
      through the Dome/Jak(Hop)/STAT92 signaling pathway to promote cell proliferation.
      Interestingly, the effect of Upd is only on cells located anterior to the
      morphogenetic furrow (MF), but has no effect on the second mitotic wave, which is
      posterior to MF. Overexpression of upd behind MF can nonautonomously induce cell
      proliferation up to 20 rows of cells anterior to MF. The G1 cyclin, cycD
      transcript level was also enhanced anterior to MF. Consistent with the long-range
      effect, we found that the extracellular Upd protein can be detected over a
      comparable long range, suggesting that Upd acts directly over a long distance as
      a signaling molecule.

PMID- 15170701
TI  - Randomized comparison of rapid ambulation using radial, 4 French femoral access,
      or femoral access with AngioSeal closure.
AB  - Radial access and closure devices are associated with improved quality of life
      (QOL) after cardiac catheterization. Whether this is related to the access site
      or time to ambulation is unknown. Seventy-five patients undergoing cardiac
      catheterization were randomized to femoral 6 Fr with AngioSeal closure (F+C),
      femoral 4 Fr without closure, and radial (R) access. All patients were ambulated
      at 1 hr. QOL was measured utilizing visual analogue scales and Short Form-36 at
      baseline, 1 day, and 1 week. Time to ambulation and discharge were equivalent, as
      was postprocedure QOL. However, angiographic quality was lower in the 4 Fr group
      (P < 0.0001) and catheterization costs were higher in the F+C group (P < 0.0001).
      Ambulation 1 hr after catheterization can be accomplished utilizing radial,
      femoral 6 Fr with closure device, or femoral 4 Fr access with equivalent outcomes
      and QOL. However, this is achieved at a higher cost with a closure device, or
      lesser angiographic quality with 4 Fr catheters.

PMID- 15170702
TI  - Point-of-care testing shows clinically relevant variation in the degree of
      inhibition of platelets by standard-dose abciximab therapy during percutaneous
      coronary intervention.
AB  - Administration of GP IIb/IIIa inhibitors during percutaneous coronary
      intervention (PCI) has proven clinical benefit, but is administered at a dose
      allowing for the patients' weight but not other variables. This study of 75
      patients evaluated platelet inhibition achieved by standard-dose abciximab
      therapy during PCI as measured by two point-of-care (POC) instruments,
      Plateletworks (PW) and whole blood aggregation (WB). Results were related to the
      decrease of platelet activation produced as well as patients' return of angina
      within 30 days. Flow cytometric measurement showed abciximab suppressed platelet
      monocyte aggregates (P < 0.001) and activated glycoprotein IIb/IIIa (P < 0.001)
      but not P-selectin. Greater POC-measured inhibition corresponded to less
      postabciximab expression of platelet-monocyte aggregates (P < 0.01). Patients
      above the lowest quartile of POC inhibition with PW demonstrated a relative risk
      of experiencing return of angina within 30 days of 0.48 (0.23-0.99). In
      conclusion, POC measurements reflect platelet activation suppression, higher PW
      measurements being associated with a decreased risk of return of angina.

PMID- 15170703
TI  - Novel use of a high-energy excimer laser catheter for calcified and complex
      coronary artery lesions.
AB  - This study was designed to evaluate safety and effectiveness of the 0.9 mm
      excimer laser coronary catheter with increased laser parameters. We report a
      prospective trial of 100 calcified and/or balloon-resistant lesions where a new
      0.9 mm excimer laser catheter was used at standard or higher energy level to
      facilitate angioplasty. Standard in-hospital clinical and angiographic parameters
      were collected and measured. Laser technical success was obtained in 87 lesions
      (92%), procedural success was reached in 88 lesions (93%), and clinical success
      in 82 lesions (86%). Increased laser parameters were used for 29 resistant
      lesions. This new 0.9 mm excimer laser coronary catheter using higher energy
      parameters seems to be safe and effective for management of calcified and
      nondilatable lesions.

PMID- 15170705
TI  - Randomized study of the safety and clinical utility of rotational angiography
      versus standard angiography in the diagnosis of coronary artery disease.
AB  - This study evaluates the safety and clinical utility of rotational angiography in
      the diagnosis of coronary artery disease. High-speed rotational angiography is a
      newly available angiographic modality that gives a dynamic multiple-angle
      perspective of the coronary tree during a single contrast injection. We
      prospectively randomized 56 patients referred for diagnostic coronary angiography
      to either standard or rotational angiography. Contrast and radiation utilization
      were compared between the two groups. The number of additional cine acquisitions
      needed was used to determine adequacy of the diagnostic study protocol.
      Rotational angiography was successfully completed in all subjects. There was a
      33% reduction in contrast utilization in the rotational group as compared to the
      standard group (35.6 +/- 12.6 vs. 52.8 +/- 10.7 ml, respectively; P < 0.0001).
      Additionally, there was a 28% reduction in total radiation exposure in the
      rotational group as compared to the standard group (39.0 +/- 18.5 vs. 53.9 +/-
      23.4 Gycm(2), respectively; P = 0.01). Total whole-body radiation exposure to the
      primary operator was 144 mrem with rotational angiography and 170 mrem with
      standard angiography. Procedure time tended to be shorter for rotational
      angiography (353.9 +/- 146.7 vs. 396.8 +/- 165.8 s; P = 0.3). Rotational coronary
      angiography can be rapidly performed in any patient and provides a significant
      reduction in contrast and radiation utilization while at the same time providing
      adequate angiographic data to complement or replace standard coronary angiography
      in the evaluation of coronary artery disease.

PMID- 15170704
TI  - Use of IIb/IIIa inhibitors in patients with in-stent restenosis treated with
      intracoronary gamma-radiation. Integrilin WRIST.
AB  - The Integrilin Washington Radiation for In-Stent Restenosis Trial (WRIST) aimed
      to study the impact of IIb/IIIa inhibitors as adjunct therapy to intracoronary
      radiation therapy (IRT) for patients with in-stent restenosis (ISR). The impact
      of GP IIb/IIIa inhibitor (eptifibatide) as adjunct therapy to vascular
      brachytherapy using (192)Ir emitter was examined in patients with in-stent
      restenosis. In the study, 150 patients were assigned to eptifibatide (Integrilin)
      and 150 patients to heparin only. Clinical composite endpoints at 30 days were
      similar between the patients treated with and without eptifibatide (4.7% vs.
      4.0%; P = 0.78). There was a similarity in the non-Q-wave myocardial infarction
      (MI) rates between the eptifibatide and the control group. Major bleeding was
      similar in patients treated with and without eptifibatide. Overall, the use of
      eptifibatide as adjunct therapy for patients with ISR that are treated with IRT
      did not impact the clinical outcome at 30 days.

PMID- 15170706
TI  - Variability in quantitative measurement of the same segment with two different
      intravascular ultrasound systems: in vivo and in vitro studies.
AB  - We evaluated two different intravascular ultrasound (IVUS) systems, Atlantis and
      Intrafocus, to verify their accuracy and reproducibility. In an in vivo study on
      20 consecutive patients with coronary artery diseases, the minimum lumen diameter
      (MLD), vessel diameter, lumen area (LA), vessel area, plaque area, and area
      stenosis rate (% AS) were respectively measured. In an in vitro study, MLD and LA
      were measured in four metal tubes with different diameters. All of the measured
      values except for % AS by Atlantis were significantly larger than the values
      obtained with Intrafocus. Nonuniform rotational distortion (NURD) was estimated
      as 34% in Atlantis and 1% in Intrafocus. The measurements by Atlantis were larger
      than the true values while the measurements by Intrafocus were less than the true
      values in all four metal tubes. These findings suggest that we should clearly
      avoid the use of different IVUS systems in the same study.

PMID- 15170707
TI  - Vascular complications following coronary intervention correlate with long-term
      cardiac events.
AB  - We aimed to study the consequences and late outcomes of patients who experienced
      peripheral vascular complications (PVCs) following percutaneous coronary
      interventions (PCI). A retrospective analysis of the medical records of 10,669
      patients who underwent PCI and experienced PVC between 1995 and 2002 was
      conducted. One thousand ninety-six patients (10.27% of the study cohort) had PVC
      post-PCI. After PCI, patients with PVC had higher rates of in-hospital
      complications (P < 0.001) when compared to patients without PVC, including Q-wave
      myocardial infarction (MI; 1.2% vs. 0.3%), coronary artery bypass grafting (CABG;
      3.8% vs. 0.6%), and death (4.0% vs. 1.0%). At 1-year follow-up, late
      complications of MI (37.4% vs. 25.4%), non-Q-wave MI (34.9% vs. 22.7%), death
      (12.9% vs. 5.9%), and CABG (5.7% vs. 4.5%) were higher (< 0.001) in patients with
      PVC compared to those without. Multivariate analysis identified PVC as a
      significant predictor of 1-year mortality (P = 0.045). This study underscores the
      need to make diligent efforts to minimize PVC and follow up these patients for
      future coronary events.

PMID- 15170708
TI  - Increase of myocardial salvage and left ventricular function recovery with
      intracoronary abciximab downstream of the coronary occlusion in patients with
      acute myocardial infarction treated with primary coronary intervention.
AB  - In this prospective randomized trial on patients with acute myocardial infarction
      (AMI) treated with primary percutaneous coronary intervention (PCI), we
      hypothesized that abciximab administered intracoronarily, downstream of the
      coronary occlusion, leads to a greater degree of myocardial salvage and better
      left ventricular function recovery compared with the usual abciximab
      administration. Forty-five consecutive patients with first AMI and infarct
      related artery TIMI flow 0-1 undergoing primary PCI were enrolled. Twenty-two
      patients were randomly assigned to the intracoronary treatment and 23 to the
      usual treatment. The initial perfusion defect, final infarct size, myocardial
      salvage, salvage index, and left ventricular function recovery were assessed by
      serial scintigraphic scans performed at admission and 7 days and 1 month after
      PCI. Angiographic myocardial blush grade, corrected TIMI frame count, and
      electrocardiographic ST segment elevation reduction were also assessed as markers
      of myocardial reperfusion. Final infarct size was significantly smaller (P =
      0.043) and salvage index significantly higher (P = 0.003) in the intracoronary
      treatment group as a result of a greater degree of myocardial salvage (P =
      0.0001). The increase of left ventricular ejection fraction at 1 month was
      significantly higher in the intracoronary treatment patients (P = 0.013). The
      markers of myocardial reperfusion were also significantly better in the
      intracoronary treatment group. In patients with AMI and occluded infarct-related
      artery treated with primary PCI, intracoronary abciximab given just before PCI
      downstream of the occlusion is associated to a greater degree of myocardial
      salvage than the usual abciximab protocol. This benefit is mainly related to a
      substantial reduction in final infarct size, which leads to an improvement in
      left ventricular ejection fraction.

PMID- 15170709
TI  - Use of statins prior to percutaneous coronary intervention reduces myonecrosis
      and improves clinical outcome.
AB  - Primary and secondary prevention with statins reduce major cardiac events in
      patients with coronary artery disease. The impact of pretreatment with statins
      prior to percutaneous coronary intervention (PCI) is not well established. The
      objective of this study was to determine if pretreatment with statins prior to
      PCI reduce myonecrosis and improve clinical outcome. One hundred nineteen
      consecutive patients with acute coronary syndrome who underwent PCI were
      identified. We compared the incidence of myonecrosis defined as peak elevation of
      CK-MB or CK three time above upper limit of normal within 24 hr and the 6-month
      cardiovascular event rate (death, nonfatal myocardial infarction unrelated to
      PCI, target vessels revascularization, and unstable angina requiring
      hospitalization) among patients who received statins prior to PCI (n = 63) to
      those who did not (n = 56). Pretreated patients were more likely to have history
      of myocardial infarction or revascularization (63% vs. 43%; P = 0.015),
      hyperlipidemia (80% vs. 48%; P = 0.001), hypertension (83% vs. 49%; P = 0.02),
      and use of angiotensin-converting enzyme inhibitor (62% vs. 38%; P = 0.008). The
      rest of baseline characteristics were similar between the two groups, including
      use of glycoprotein IIb/IIIa inhibitors, number of diseased vessels, and type of
      lesions. Patients pretreated with statins had a significantly lower incidence of
      myonecrosis (2% vs. 10%; P = 0.04) at 24 hr and a significantly lower clinical
      event (CE) rate at 6 months (17% vs. 21%; P = 0.015). Of patients not pretreated
      with statins, 72% were taking statins at 6 months as compared to 98% of
      pretreated patients. After adjusting for all baseline characteristics, use of
      statins prior to PCI was associated with a marked decrease in risk of all CEs (OR
      = 0.2; CI = 0.06-0.63; P = 0.006). Statin therapy prior to PCI may reduces peri
      PCI myonecrosis and late cardiac events. These results need to be confirmed in
      large prospective randomized trials.

PMID- 15170711
TI  - Regression of coronary in-stent restenosis.

PMID- 15170710
TI  - First human experience with stent-based ventricle-to-coronary artery bypass.
AB  - Stent-based ventricle-to-coronary artery bypass (VSTENT) has been shown
      experimentally to provide systolic instead of physiological diastolic blood flow
      directly from the left ventricle to a coronary artery distal to a high-grade
      stenosis. We report on the first successful surgical implantation of a VSTENT in
      a patient with coronary artery disease. At 3-month follow-up, the VSTENT was
      patent and showed sufficient regional blood flow at rest with a significant flow
      reserve. In addition, the patient was asymptomatic during exercise testing.
      Though encouraging, these observations have to be confirmed and are the subject
      of an ongoing multicenter study.

PMID- 15170712
TI  - Early ostial saphenous vein graft stenosis associated with the use of Symmetry
      sutureless aortic proximal anastomosis device: successful percutaneous
      revascularization.
AB  - A recent advance in technology permits the creation of sutureless proximal aortic
      anastomosis during coronary artery bypass graft surgery. This new tool has
      significant potential benefit by minimizing aortic manipulation with subsequent
      reduction in neuroembolization. Implantation of a nitinol-based proximal aortic
      connector (Symmetry) has a potential to elicit intimal hyperplastic reaction
      analogous to restenosis after coronary stent placement. We report cases of early
      vein graft stenosis in association with the use of the Symmetry device. Three
      patients suffered from severe ostial stenosis within 6 months of bypass surgery
      with symptomatic presentation. Of these three patients, two underwent successful
      percutaneous revascularization. Fluoroscopic star-shaped appearance of the
      metallic Symmetry allows device recognition during angiography. We review current
      data regarding graft patency with the use of Symmetry device and discuss
      technical issues to address specific problems during percutaneous
      revascularization.

PMID- 15170713
TI  - Bivalirudin-associated intracoronary thrombosis during gamma-brachytherapy and
      its experimental validation in acute swine model.
AB  - Bivalirudin is indicated for use as an anticoagulant in patients with unstable
      angina undergoing percutaneous transluminal coronary angioplasty. Cases of
      intracoronary thrombosis have been reported with beta-radiation when bivalirudin
      is used as an anticoagulant. We report two cases of intracoronary thrombosis with
      gamma-radiation when bivalirudin is used.

PMID- 15170714
TI  - Double-wire technique for access into a protruding aorto-ostial stent for
      treatment of in-stent restenosis.
AB  - We report a case of restenosis following ostial stenting of the right coronary
      artery with protrusion of the stent into the aorta. Treatment was only possible
      after a guidewire advanced through a lower strut was used to lever the guide, and
      a second guidewire was advanced through the true lumen.

PMID- 15170715
TI  - Frugal coronary angioplasty: a case for the simple approach.

PMID- 15170716
TI  - Validation of a thermographic guidewire for endoluminal mapping of
      atherosclerotic disease: an in vitro study.
AB  - Temperature heterogeneity along the inner surface of an artery may be a surrogate
      marker of impending plaque rupture and has been associated with an increased
      likelihood of future coronary events. Initial studies using catheter-based
      thermographic devices have demonstrated that the changes in temperature are
      subtle, while the effects of coronary flow on measured temperature have not yet
      been examined. A novel guidewire-based system (ThermoCoil, Imetrx) designed to
      measure surface temperature in coronary arteries was used to study the effects of
      heat source intensity and flow on measured temperature. An in vitro model of a
      focal, eccentric, heat-generating lesion demonstrated that a guidewire-based
      system can detect changes in surface temperature with a precision of less than
      0.08 degrees C. In this model, temperature measurements increased linearly with
      source temperature and decreased with increases in flow by an exponent of -0.33
      (P < 0.001 for both). Flow rates and heat source properties can significantly
      influence the measurement and interpretation of thermographic data. The
      incorporation of 2D thermographic images may contribute further to the
      characterization of metabolically active plaques likely to cause acute coronary
      syndromes.

PMID- 15170717
TI  - Percutaneous revascularization of the common femoral artery for limb ischemia.
AB  - We performed percutaneous transluminal intervention in 20 consecutive patients
      (21 limbs) with common femoral artery (CFA) lesions causing symptomatic limb
      ischemia. In 12 limbs, concurrent additional percutaneous intervention proximal
      or distal to the target CFA lesion was performed. Angiographic success was
      obtained in 100%, with procedural success (angiographic success without a major
      in-hospital complications) in 90% and clinical success (procedural success and in
      hospital improvement by at least one Fontaine functional class) in 81% of the
      limbs. The in-hospital Fontaine class improved by at least one functional class
      in 17 of 19 patients (89%), and the overall in-hospital event-free survival was
      90% (18 of 20 patients). At follow-up (11.4 +/- 6 months), the overall event-free
      survival was 90% (18 of 20 patients) and 17 of 19 patients (89%) continue to show
      improvement by at least one functional (Fontaine) class. Percutaneous
      intervention of the CFA can be performed with a rate of high technical success
      and a low complication rate. It provides excellent clinical results at mid-term
      follow-up and appears to be a reasonable alternative to surgical therapy in
      patients at high risk for surgery.

PMID- 15170719
TI  - Utility of IVUS-guided transaccess catheter in the treatment of long chronic
      total occlusion of the superficial femoral artery.
AB  - Failure to reenter the true lumen distal to an occlusion is the most frequent
      cause of failure of the technique of subintimal angioplasty. We report the
      utility of an IVUS-guided TransAccess catheter in overcoming this problem in the
      treatment of two patients with long chronic total occlusion of the superficial
      femoral artery.

PMID- 15170718
TI  - Complication with an embolic protection device during carotid angioplasty.
AB  - A case of carotid artery stenting with an AngioGuard cerebral protection device
      is described in a patient with tight internal carotid stenosis. Deployment of
      AngioGuard induced sudden severe vasospasm, with subsequent minor stroke.
      According to our observations, AngioGuard may cause a vasospastic response with
      adverse neurologic effects.

PMID- 15170720
TI  - Concomitant coronary and subclavian steal caused by ipsilateral subclavian artery
      stenosis and arteriovenous fistula in a hemodialysis patient.
AB  - Patients with chronic renal failure, because of concomitant conventional
      cardiovascular and uremia-associated risk factors, are at risk of developing
      diffuse and accelerated atherosclerosis involving both the coronary and
      peripheral territories. We report an end-stage renal failure patient with a
      history of coronary artery bypass surgery who developed both angina and dizziness
      during hemodialysis via a left forearm arteriovenous fistula. Magnetic resonance
      imaging diagnosed the presence of significant subclavian artery stenosis. The
      patient then underwent successful percutaneous stenting of the left subclavian
      artery. His angina and dizziness symptoms resolved subsequently.

PMID- 15170721
TI  - Intra-arterial thrombolysis for left middle cerebral artery embolic stroke during
      percutaneous mitral commissurotomy.
AB  - Cerebral thromboembolism is a serious complication. Early recognition and rapid
      reperfusion can prevent long-term neurological morbidity. We report a case of
      successful intra-arterial thrombolysis for middle cerebral artery embolic stroke
      during percutaneous mitral commissurotomy, which resulted in complete
      neurological recovery.

PMID- 15170722
TI  - Aortic aneurysm repair with endovascular grafts: developing a graft surveillance
      program.
AB  - The objective of this study was to describe the development of a comprehensive
      surveillance program for monitoring the long-term follow-up of endoluminal stent
      graft (ELG) patients. Despite high procedural success rates, ELG patients remain
      at ongoing risk for aneurysm sac expansion, rupture, and other adverse events
      that make long-term surveillance imperative. As they perform more ELG,
      practitioners face increased logistical difficulty performing appropriate patient
      follow-up. A computer-based data ELG registry was created using Epi Info, a
      program developed by the Centers for Disease Control and Prevention that enables
      users to design a data entry form, enter data, and perform statistical analyses.
      The database has been used to track 259 patients (214 men and 45 women) who
      underwent ELG between November 1999 and October 2003. One-year follow-up was
      available for 182 patients, 2-year follow-up for 104 patients, and 3-year
      surveillance data for 40 patients, which represent follow-up rates of 89.6%,
      78.8%, and 61.5%, respectively. There were 25 late deaths. The Kaplan-Meier
      estimate for 1-year survival was 92.5%. Twenty-one patients underwent 24
      secondary angiographic procedures at a mean 8.6 +/- 10.3 months (range, 1-37.6)
      after stent-graft repair. No mortality was observed in association with a
      secondary intervention. There were no late conversions to open aneurysm repair.
      The Kaplan-Meier estimate for freedom from secondary intervention for all
      patients at 1 year was 91.0%. A computer-based registry facilitates appropriate
      and timely patient follow-up and may improve the long-term outcome from ELG.

PMID- 15170723
TI  - Percutaneous closure of atrial septal defect via transjugular approach with the
      Amplatzer septal occluder after unsuccessful attempt using the CardioSEAL device.
AB  - Percutaneous closure of a secundum atrial septal defect was performed
      successfully via the jugular approach in a 77-year-old patient with heparin
      induced thrombocytopenia and total occlusion of the inferior vena cava using the
      Amplatzer septal occluder after an unsuccessful attempt using the CardioSEAL
      septal occluder. This case demonstrates the advantages of the jugular approach in
      the patient with difficult anatomy and the advantage of the Amplatzer over the
      CardioSEAL device in this situation.

PMID- 15170724
TI  - Bioptome-assisted coil occlusion of moderate-large patent ductus arteriosus in
      infants and small children.
AB  - Coil occlusion of patent ductus arteriosus (PDA), although inexpensive, is
      technically challenging for the moderate-large ducts in small children. Bioptome
      assistance allows better control and precision. We describe case selection
      strategies, technique, immediate and short-term results of bioptome-assisted
      closure of moderate-large (>/= 3 mm) PDA in 86 infants and children </= 10 kg
      (age, 18 days to 3 years; median, 8 months; weight, 6.6 +/- 1.9 kg; duct size,
      3.6 +/- 0.8 mm; pulmonary artery mean pressures, 33 +/- 12 mm Hg). Patients with
      PDA > 6 mm (> 4 mm for children under 5 kg) and/or shallow ampullae (by
      echocardiography) underwent operation (n = 41). Specific technical modifications
      included use of long sheaths (5.5-8 Fr) for duct delineation and coil delivery,
      cutting of coils turns (51 patients) to accommodate the coils in the ampulla, and
      simultaneous delivery of multiple coils (n = 43). As far as possible, coils were
      deployed entirely in the ampulla. Median fluoroscopy time was 7.3 min (1.2-42
      min). Successful deployment was feasible in all (final pulmonary artery mean
      pressures, 20 +/- 4.6 mm Hg). Coils embolized in 14 (16%) patients (all
      retrieved). Complete occlusion occurred immediately in 63 patients (73%) and in
      77 patients (89%) at 24 hr. Three patients had new gradients in the left
      pulmonary artery. Follow-up (62 patients; median duration, 13 months) revealed
      small residual Doppler flows in 11 patients (18%) at the most recent visit.
      Bioptome-assisted coil occlusion of moderate-large PDA in selected infants and
      small children is feasible with encouraging results.

PMID- 15170725
TI  - Should we be using bilateral carotid distal protection devices during the
      percutaneous closure of patent foramen ovale in patients with a history of
      paradoxical embolus?
AB  - Percutaneous closure of patent foramen ovale (PFO) is becoming standard practice,
      particularly in patients with a history of embolic phenomena. The acute risk of
      cerebrovascular accident in patients undergoing this procedure is approximately
      1%. We report the first successful use of bilateral carotid artery distal
      protection in this situation.

PMID- 15170726
TI  - Device closure of iatrogenic membranous ventricular septal defects after
      prosthetic aortic valve replacement using the Amplatzer membranous ventricular
      septal defect occluder.
AB  - Iatrogenic hemodynamically significant ventricular septal defects (VSDs) after
      aortic valve replacement are rare. The surgical risk to close such VSDs is
      substantial. Catheter closure has rarely been attempted because access to the
      left ventricle during cardiac catheterization in patients with a prosthetic
      aortic valve has been associated with a risk of catheter entrapment. We describe
      two cases of this rare entity after St. Jude and Medtronic valve replacement in
      which successful percutaneous closure of the iatrogenic VSDs was achieved using
      the Amplatzer membranous VSD occluder. Crossing the prosthetic valves with a
      delivery sheath and closure with the membranous VSD device was accomplished in
      both cases.

PMID- 15170727
TI  - Coronary artery stent infection.

PMID- 15170728
TI  - Management of radial artery spasm.

PMID- 15170730
TI  - Gene therapy clinical trials worldwide 1989-2004-an overview.
AB  - In 1989, Rosenberg et al. performed the first human gene therapy trial when they
      used a retrovirus to introduce the gene coding for resistance to neomycin into
      human tumor-infiltrating lymphocytes before infusing them into five patients with
      advanced melanoma. This study demonstrated the feasibility of using retroviral
      gene transduction in humans and set the stage for further studies. Since then,
      over 900 clinical trials have been completed, are ongoing or have been approved
      worldwide. These trials have been designed to establish feasibility and safety,
      to demonstrate the reality of expression of therapeutic protein(s) in vivo by the
      genes transferred and, in some cases, to show therapeutic benefit. There is no
      single source of information that presents an overview of all the clinical trials
      undertaken worldwide. In 1997 we set up a database to bring all the information
      on clinical trials together as comprehensively and as globally as possible. The
      data were compiled and are regularly updated from official agency sources, the
      published literature, presentations at conferences and from information kindly
      provided by investigators or trial sponsors themselves. As of January 31, 2004,
      we have identified 918 trials in 24 countries. The USA accounts for two-thirds of
      these trials. Cancer is by far the most common disease indication, followed by
      inherited monogenic diseases, and cardiovascular diseases. Viral vectors have
      been the most frequently used vehicles for transferring genes into human cells,
      with retroviruses and adenoviruses representing the vast majority. Plasmid
      (naked) DNA and other non-viral vectors have been used in one-quarter of the
      trials. Over 100 distinct genes have been transferred. This article aims to
      provide a descriptive overview of the clinical trials that, to the best of our
      knowledge, have been or are being performed worldwide. Details of the data
      presented, including an interactive, searchable database that currently holds
      information on 918 trials, can be found on The Journal of Gene Medicine clinical
      trials website 1.

PMID- 15170731
TI  - Enhancer-deleted retroviral vectors restore high levels of superoxide generation
      in a mouse model of CGD.
AB  - BACKGROUND: Retroviral vectors possess many advantages for use in gene therapy
      protocols, especially within the haematopoietic system. A number of attendant
      problems, however, still limit their safety in clinical application. The effects
      of the enhancer present in the retroviral long terminal repeat (LTR) are a major
      concern for the clinical usage of such vectors, as they can exert a powerful
      regulatory influence on the genes that surround them. METHODS: To improve the
      safety and widen the applicability of retroviral vectors for use in gene therapy
      we have developed an enhancer-deleted (Delta-LTR) retroviral vector that retained
      high titre and demonstrated transcriptional activity in myeloid cells. RESULTS:
      When used to correct a mouse model of autosomal recessive chronic granulomatous
      disease, the Delta-LTR vectors gave acceptable levels of gene transfer to mouse
      bone marrow cells. Evidence for a slight preferential expression in myeloid cells
      was obtained with all the vectors studied. Nitroblue tetrazolium assay of
      superoxide generation in mouse bone marrow derived haematopoietic colonies
      revealed that transduction with Delta-LTR vectors could restore functional NADPH
      oxidase to cells from these animals. Superoxide assay of peripheral blood
      confirmed that, although relatively low numbers of cells were transduced, the
      Delta-LTR vector was capable of reconstituting very high levels of oxidase
      activity, comparable to that obtained from normal cells. CONCLUSIONS: The Delta
      LTR vector described here could provide the basis for a new generation of
      retroviral vectors with improved safety.

PMID- 15170732
TI  - Decline of surface MHC I by adenoviral gene transfer of anti-MHC I intrabodies in
      human endothelial cells-new perspectives for the generation of universal donor
      cells for tissue transplantation.
AB  - BACKGROUND: The seeding of small-calibre vascular polytetrafluoroethylene (PTFE)
      grafts with endothelial cells provides an increase in biocompatibility of the
      graft surface. The harvest and ex vivo culture of autologous endothelial cells is
      highly delicate. Allogeneic human umbilical vein endothelial cells (HUVEC) could
      be a potential cell source-however, rejection might occur due to major
      histocompatibility complex (MHC) I mismatches. Lowering cell surface MHC I
      expression on endothelial cells by gene transfer of an anti-MHC I intrabody might
      reduce graft failure. The intrabody consists of a single-chain variable fragment
      (sFv) of an anti-MHC I antibody, carrying a terminal KDEL sequence to retain the
      molecule together with the MHC I inside the endoplasmic reticulum. METHODS:
      Adenoviral gene transfer was used to express the intrabody in HUVEC. The MHC I
      surface expression was measured 48 h after transduction by flow cytometry.
      Functional effects of the intrabody expression were analyzed in a calcein release
      cytotoxicity assay. RESULTS: A transduction efficiency of more than 95% with EGFP
      adenovirus indicates a sufficient gene transfer into HUVEC. Intrabody-adenovirus
      transduced HUVEC show a massive reduction in MHC I surface expression creating
      almost a complete 'knockout' phenotype. Stimulation with inflammatory cytokines
      could not overcome this effect. The cell lysis of anti-MHC I intrabody-expressing
      HUVEC in a cytotoxicity assay is reduced when compared with the level of the MHC
      mismatched control. CONCLUSIONS: Our data indicate that HUVEC with reduced levels
      of MHC I might be used as universal donor cells for the seeding of vascular
      grafts.

PMID- 15170733
TI  - Hepatocyte growth factor stimulates adenoviral-mediated gene transfer across the
      apical membrane of epithelial cells.
AB  - BACKGROUND: The apical surface of polarized epithelial cells is relatively
      resistant to gene delivery by various agents including adenoviral vectors.
      Hepatocyte growth factor (HGF) dedifferentiates previously well-polarized Madin
      Darby canine kidney (MDCK) cell monolayers by altering cell-surface polarity and
      inhibiting tight junction function. METHODS: We used an in vitro model of
      polarized MDCK cells grown on permeable supports to examine the effects of HGF
      pretreatment on adenoviral (Ad)-mediated gene delivery through the apical surface
      of epithelial cell monolayers. RESULTS: HGF pretreatment of MDCK cell monolayers
      for 72 h increased Ad-mediated gene transfer and expression of enhanced green
      fluorescent protein (EGFP) and luciferase in a dose-dependent fashion. Time
      course analysis of HGF-induced stimulation of Ad-mediated gene transfer was seen
      after 24 h and increased further with pretreatment periods extending to 72 h. HGF
      pretreatment increased Ad-mediated gene transfer at varying multiplicity of
      infection (MOI; ranging from 0.2-2000). PCR analysis for adenoviral DNA in
      control and HGF-pretreated MDCK cells suggested increased entry of viral
      constructs into HGF-pretreated MDCK cell monolayers. HGF-induced alterations in
      cell polarity are reversible upon removal of HGF. CONCLUSIONS: These data
      demonstrate that HGF pretreatment of MDCK cells increases the sensitivity of the
      cells to Ad-mediated gene delivery. The mechanism by which this occurs appears to
      be through increased entry of adenovirus into epithelial cells. These data
      provide evidence that biological agents that transiently alter epithelial cell
      polarity and tight junction function can be used to augment Ad-mediated gene
      delivery into epithelial cells from the apical surface.

PMID- 15170735
TI  - Recombinant bispecific antibodies for the targeting of adenoviruses to CEA
      expressing tumour cells: a comparative analysis of bacterially expressed single
      chain diabody and tandem scFv.
AB  - We have generated two distinct recombinant bispecific antibody molecules for the
      retargeting of adenoviral vectors to CEA-expressing tumour cells. These antibody
      molecules were produced by combining the antigen-binding sites of a neutralising
      anti-fibre knob scFv (S11) and an anti-CEA antibody either in a single-chain
      diabody format (scDb CEA-S11) or a tandem scFv format (taFv CEA-S11). In order to
      facilitate expression of taFv CEA-S11 in bacteria we selected from a phage
      display library taFv molecules with an optimised linker that connects the two
      scFv fragments. ScDb CEA-S11 and taFv CEA-S11 were expressed and purified in
      soluble form from the bacterial periplasm with yields of approximately 100 micro
      g per litre of bacterial culture. In vitro, both bispecific molecules mediated
      selective and enhanced transduction of CEA-expressing tumour cells by recombinant
      adenoviruses. These assays did not reveal any differences in efficiency of
      adenoviral transduction by the two antibody formats. However, compared with taFv
      CEA-S11, scDb CEA-S11 exhibited a 2- to 3-fold increased stability in human
      plasma at 37 degrees C. In summary, we could demonstrate that both formats are
      suitable for adenovirus targeting to tumour cells with similar biological
      activity in vitro.

PMID- 15170734
TI  - Development of an adenoviral vector system with adenovirus serotype 35 tropism;
      efficient transient gene transfer into primary malignant hematopoietic cells.
AB  - BACKGROUND: A paucity of coxsackie adenovirus receptor (CAR) hampers the
      adenovirus serotype 5 (Ad5)-based vector-mediated gene transfer into malignant
      hematopoietic cells. Fiber-retargeted adenoviral vectors with species B tropism
      can potentially bypass the CAR requirement and facilitate efficient gene transfer
      into malignant hematopoietic cells. METHODS: For feasible generation of fiber
      retargeted adenoviral vectors, we have modified the versatile AdEasy system with
      a chimeric fiber gene encoding the Ad5 fiber tail domain and Ad35 fiber shaft and
      knob domains. An Ad5-based vector encoding the green fluorescent protein (GFP)
      gene under the control of the PGK promoter with Ad35 fiber receptor specificity
      was generated (Ad5F35-GFP). The Ad5F35-GFP vector-mediated gene transfer
      efficiency was compared with a fiber non-modified Ad5-GFP vector, which also
      encodes the GFP gene under the control of the PGK promoter. RESULTS: We
      demonstrated that a variety of Ad5-refractory malignant myeloid and B lymphoid
      cell lines were highly permissive to the Ad5F35-GFP vector infection.
      Importantly, primary chronic myeloid leukemic (CML) cells and chronic lymphocytic
      leukemia (CLL) B cells were superiorly transduced by the Ad5F35-GFP vector at a
      multiplicity of infection (MOI) of 100 compared with the Ad5-GFP vector.
      CONCLUSIONS: Our study will facilitate the generation of fiber-retargeted
      adenoviral vectors and enable transient genetic manipulation of primary malignant
      hematopoietic cells.

PMID- 15170736
TI  - Trans-complementing adenoviral vectors for oncolytic therapy of malignant
      melanoma.
AB  - BACKGROUND: Despite attempts to develop efficient viral-based gene transfer
      therapies for the treatment of malignant tumors, only limited progress has been
      made to improve the efficacy of this approach. As an alternative, the use of
      replicating oncolytic adenoviruses with and without the expression of therapeutic
      transgenes is an area of active investigation. METHODS: We used a human melanoma
      xenograft tumor nude mouse model to test the efficacy of a bivalent vector
      approach consisting of two trans-complementing replication-incompetent adenoviral
      vectors that resulted in tumor-restricted oncolysis. We combined an E1-deleted
      non-replicating adenoviral vector expressing the herpes simplex virus thymidine
      kinase gene (AV.C2.TK) and Ad5.dl1014, an E4-deleted/E4orf4-only expressing
      adenovirus, to allow full replication competence when tumor cells were co
      infected with both vectors. RESULTS: A375 tumors showed apoptosis at the
      ultrastructural level after transduction with the trans-complementing vector
      system that was not seen with injection of either vector alone. Apoptotic DNA
      fragments could be co-localized to sites of infection with the adenoviral
      vectors. A significant survival benefit was achieved for the trans-complementing
      vector treated animals compared to animals treated with either vector alone.
      Interestingly, the administration of GCV did not further increase animal survival
      over treatment with the trans-complementing system of viruses alone, and long
      term survival was only seen in the trans-complementing vector treatment group.
      Intraperitoneal administration of a pseudo-wild-type vector Ad.dl327 resulted in
      significant hepatotoxicity, while intraperitoneal administration of the trans
      complementing vectors resulted in only mild liver abnormalities. CONCLUSIONS: The
      trans-complementing vector approach using a combination of E1- and E4-deleted
      adenoviral vectors showed similar antitumor efficacy as reported for monovalent
      replicating vector systems, but may offer additional safety by reducing the risk
      of dissemination of the replication-competent vectors by requiring the presence
      of both vectors in a cell to achieve replication competence.

PMID- 15170737
TI  - Gene therapy with novel adeno-associated virus vectors substantially diminishes
      atherosclerosis in a murine model of familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia is an inherited disease caused by
      mutations in the LDL receptor gene leading to severe hypercholesterolemia and
      atherosclerosis. The LDL receptor is predominantly expressed in the liver, making
      it a preferred target organ for somatic gene therapy. We recently isolated a new
      family of vectors based on adeno-associated viruses (AAVs) isolated from nonhuman
      primates, which enable efficient and stable transgene expression following in
      vivo gene delivery to liver. METHODS: Traditional vectors based on AAV serotype 2
      and two novel AAVs from nonhuman primates, serotypes AAV7 and AAV8, were produced
      encoding for the human LDL receptor. Vectors were injected into the portal veins
      of LDL receptor deficient mice that were fed a high-fat diet to achieve severe
      pretreatment hypercholesterolemia. RESULTS: Animals receiving the novel AAV
      vectors realized nearly complete normalization of serum lipids and failed to
      develop the severe atherosclerosis that characterized the untreated animals; the
      AAV2 vector constructs demonstrated partial lipid correction and only a modest
      improvement in atherosclerosis. CONCLUSIONS: Using vectors based on novel
      nonhuman primate AAVs, which provide advantages in terms of efficiency, we were
      able to achieve a long-term correction of the metabolic defect in LDL receptor
      deficient mice.

PMID- 15170738
TI  - Use of the radiation-inducible WAF1 promoter to drive iNOS gene therapy as a
      novel anti-cancer treatment.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) gene therapy has been
      identified as a potential anti-tumour strategy. A major problem common to most
      gene therapy strategies is targeting of treatment to the tumour volume. In this
      study we report on the use of the X-ray-inducible WAF1 promoter to achieve
      targeting of iNOS expression to the tumour volume. METHODS: A WAF1/iNOS/liposome
      complex was injected directly into RIF-1 and HT29 tumours in mice. A 4 Gy dose of
      X-rays was applied to induce the WAF1 promoter followed, 8 h later, by treatment
      doses of 10 or 20 Gy. Tumour volume was measured, and growth curves plotted.
      RESULTS: Intra-tumoural injection of WAF1/iNOS combined with a priming dose of X
      rays to induce the WAF1 promoter, followed by a treatment dose, resulted in
      sensitiser enhancement ratios of 2.0 and 1.3 in RIF-1 and HT29 tumours,
      respectively, compared with radiation treatment alone. PCR analysis of organ
      tissue after intra-tumoural injection of WAF1/iNOS showed that vector sequences
      were detected in all tissue tested; however, Western blot analysis revealed that
      iNOS protein levels were significantly increased only in tumour and the
      surrounding dermal tissue that had been exposed to the 4 Gy inducing dose.
      CONCLUSIONS: iNOS gene therapy in combination with an inducible promoter results
      in significant tumour cell radiosensitisation. The WAF1 promoter may be a good
      candidate for a gene therapy as it is silent in normal tissue yet can be induced
      by the tumour environment.

PMID- 15170739
TI  - Association of albumin or protamine to lipoplexes: enhancement of transfection
      and resistance to serum.
AB  - BACKGROUND: The successful application of gene therapy depends on the
      availability of carriers to efficiently deliver genetic material into target
      cells. Such efficacy is strongly related to key parameters including serum
      resistance and protection of DNA. METHODS: The complexes were tested in terms of
      their biological activity, in the absence or presence of serum, by following
      transfection activity. Interaction with plasma proteins was evaluated by
      immunoblotting, while cytotoxicity was assessed by the Alamar Blue assay. Extent
      of DNA protection was determined both by using ethidium bromide intercalation and
      DNase I digestion assays. RESULTS: Our results show that, depending on the charge
      ratio and on the lipid composition, albumin and protamine can be used (either
      individually or co-associated) to generate cationic liposome/DNA complexes
      fulfilling in vivo requirements, while exhibiting high levels of transfection
      activity. In the present work a novel cationic lipid was tested. It was
      demonstrated that 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine
      (EPOPC):cholesterol (Chol) liposomes constitute a very promising carrier for gene
      delivery as illustrated by their enhancing effect on transfection, as compared
      with DOTAP-containing liposomes. Moreover, the biological activity of EPOPC
      containing complexes is significantly improved upon association of albumin, even
      in the presence of 60% serum (namely for the 4/1 lipid/DNA charge ratio).
      Nevertheless, our studies also show that transfection activity mediated by DOTAP
      containing complexes can be significantly enhanced upon pre-condensation of DNA
      with protamine. CONCLUSIONS: Co-association of HSA and protamine to lipoplexes
      ensures a high degree of DNA protection and results in high levels of
      transfection activity even in the presence of serum.

PMID- 15170740
TI  - Regional hydrodynamic gene delivery to the rat liver with physiological volumes
      of DNA solution.
AB  - BACKGROUND: The major barrier to the clinical application of hydrodynamic gene
      delivery to the liver is the large volume of fluid required using standard
      protocols. Regional hydrodynamic gene delivery via branches of the portal vein
      has not previously been reported, and we have evaluated this approach in a rat
      model. METHODS: The pGL3 plasmid with the luciferase reporter gene was used at 50
      micro g/ml in isotonic solutions, and was administered with a syringe pump for
      precise control of the hydrodynamic conditions evaluated. Gene expression was
      individually measured in six anatomically distinct liver lobes. The effect of
      systemic chloroquine to promote endocytic escape and a (Lys)(16)-containing
      peptide to condense the DNA into approximately 100-nm nanoparticles was also
      evaluated. RESULTS: Hydrodynamic conditions for excellent gene delivery were
      obtained by using 3-ml volumes ( approximately 12 ml/kg) of isotonic DNA solution
      delivered at 24 ml/min to the right lateral lobe ( approximately 20% of the liver
      mass). Under these conditions, >95% of gene delivery usually occurred in the
      targeted right lateral lobe. Outflow obstruction was essential for gene delivery,
      both at optimal and at very low levels of hydrodynamic gene delivery. The use of
      systemic chloroquine to promote endocytic escape did not augment hydrodynamic
      gene delivery, while condensation of DNA in non-ionic isotonic solutions (5%
      dextrose) to nanoparticles of approximately 100 nm completely abolished gene
      delivery. CONCLUSIONS: Regional hydrodynamic gene delivery via a branch of the
      portal vein offers a physiological model of liver gene therapy, for experimental
      and clinical application.

PMID- 15170741
TI  - Genetic engineering of cytolytic T lymphocytes for adoptive T-cell therapy of
      neuroblastoma.
AB  - BACKGROUND: Disease relapse is the leading cause of mortality for children
      diagnosed with disseminated neuroblastoma. The adoptive transfer of tumor
      specific T cells is an attractive approach to target minimal residual disease
      following conventional therapies. We describe here the genetic engineering of
      human cytotoxic T lymphocytes (CTL) to express a chimeric immunoreceptor for re
      directed HLA-independent recognition of neuroblastoma. METHODS: The CE7R chimeric
      immunoreceptor was constructed by PCR splice overlap extension and is composed of
      a single-chain antibody extracellular domain (scFv) derived from the L1-CAM
      specific murine CE7 hybridoma fused to human IgG1 hinge-Fc, the transmembrane
      portion of human CD4, and the cytoplasmic tail of huCD3-zeta chain (scFvFc:zeta).
      Primary human T cells were genetically modified by naked DNA electrotransfer of
      plasmid expression vector CE7R-pMG then analyzed by Western blotting, flow
      cytometry for CE7R expression and cell surface trafficking, 4-h chromium release
      assay for re-directed neuroblastoma lysis, and ELISA for tumor-specific
      activation of cytokine production. RESULTS: CE7R is expressed as an intact
      chimeric protein that trafficks to the cell surface as a type I transmembrane
      protein. Primary human CE7R-expressing CD8(+) CTL clones specifically recognize
      human neuroblastoma tumor cells and are activated for tumor cell lysis and T(c)1
      cytokine production. CONCLUSIONS: These data demonstrate the utility of CE7R for
      re-directing the effector function of CTL to neuroblastoma and have provided the
      rationale to initiate a FDA-authorized (BB-IND#9149) pilot clinical trial to
      establish the feasibility and safety of adoptive transfer of autologous
      CE7R(+)CD8(+) CTL clones to children with recurrent/refractory neuroblastoma.

PMID- 15170743
TI  - A digital ion trap mass spectrometer coupled with atmospheric pressure ion
      sources.
AB  - In a digital ion trap (DIT), the quadrupole trapping and excitation waveforms are
      generated by the rapid switching between discrete d.c. voltage levels. As the
      timing of the switch can be controlled precisely by digital circuitry, the
      approach provides an opportunity to generate mass spectra by means of a frequency
      scan in contrast to the conventional voltage scan, thus providing a wider mass
      range of analysis. An instrument has been constructed which employs a 'non
      stretched' ion trap and the field fault around the aperture of the end-cap
      electrode can be corrected electronically using a field-adjusting electrode. The
      ion trap was coupled with electrospray ionization (ESI) and atmospheric pressure
      matrix-assisted laser desorption/ionization (AP-MALDI) sources to demonstrate the
      capability of the digital method. AP-MALDI mass spectra of singly charged ions
      with mass-to-charge ratios upto 17 000 Th were generated using a trapping voltage
      of only 1000 V. Forward and reverse mass scans at resolutions up to 19 000 and
      precursor ion isolation at resolutions up to 3500 with subsequent tandem mass
      spectrometric analysis were demonstrated. The method of generating the digital
      waveforms and period scan is described. Discussion of the issues of mass range,
      scan speed, ion trapping efficiency and collision-induced dissociation efficiency
      are also provided.

PMID- 15170744
TI  - Simultaneous determination of mono-, di- and tributyltin in environmental samples
      using isotope dilution gas chromatography mass spectrometry.
AB  - The development of a rapid, precise and accurate speciation method for the
      simultaneous determination of mono-, di- and tributyltin in environmental samples
      is described. The method is based on using isotope dilution gas
      chromatography/mass spectrometry (GC/MS) with electron ionization, a widely used
      technique in routine testing laboratories. A mixed spike containing (119)Sn
      enriched monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) was used for
      the isotope dilution of the samples. Five molecular ions were monitored for each
      analyte, corresponding to the (116)Sn, (117)Sn, (118)Sn, (119)Sn and (120)Sn
      isotopes. The detection at masses corresponding to (116)Sn and (117)Sn were used
      to correct for m + 1 and m + 2 contributions of (13)C from the organic groups
      attached to the tin atom on the (118)Sn, (119)Sn and (120)Sn masses with simple
      mathematical equations and the concentrations of the butyltin compounds were
      calculated based on the corrected (118)Sn/(119)Sn and (120)Sn/(119)Sn isotope
      ratios. The (119)Sn-enriched multispecies spike was applied with satisfactory
      results to the simultaneous determination of MBT, DBT and TBT in three certified
      reference materials: two sediments, PACS-2 and BCR 646, and the mussel tissue CRM
      477. The method was compared with a previously published GC/inductively coupled
      plasma MS isotope dilution procedure, developed in our laboratory, by injecting
      the same samples into both instruments. Comparable analytical results in terms of
      precision and accuracy are demonstrated for both atomic and molecular mass
      spectrometric detectors. Thus, reliable quantitative organotin speciation
      analysis can be achieved using the more widespread and inexpensive GC/MS
      instrument.

PMID- 15170745
TI  - Influence of "alternative" C-terminal amino acids on the formation of [b3 + 17 +
      Cat]+ products from metal cationized synthetic tetrapeptides.
AB  - The aim of this study was to investigate the dissociation patterns, and in
      particular the relative abundance of [b(3) + 17 + Cat](+), for peptides with C
      termini designed to allow transfer of the -OH required to generate the product
      ion, but not necessarily as the most favored pathway. Working with the hypothesis
      that formation of a five-membered ring intermediate, including intramolecular
      nucleophilic attack by a carbonyl oxygen atom, is an important mechanistic step,
      several model peptides with general sequence AcFGGX were synthesized, metal
      cationized by electrospray ionization and subjected to collision-induced
      dissociation (CID). The amino acid at position X was one that either required a
      larger ring intermediate (beta-alanine, gamma-aminobutyric acid and epsilon-amino
      n-caproic acid to generate six-, seven- or nine- membered rings, respectively) to
      transfer -OH, lacked a structural element required for nucleophilic attack
      (aminoethanol) or prohibited cyclization because of the inclusion of a rigid ring
      (p- and m-aminobenzoic acid). For Ag(+), Li(+) and Na(+) cationized peptides, our
      results show that amino acids requiring the adoption of larger ring intermediates
      suppressed the formation of [b(3) + 17 + Cat](+), while amino acids that prohibit
      cyclization eliminated the reaction pathway completely. Formation of [b(3) - 1 +
      Cat](+) from the alkali metal cationized versions was not a favorable process
      upon suppression or elimination of the [b(3) + 17 + Cat](+) pathway: the loss of
      H(2)O to form [M - H(2)O + Cat](+) was instead the dominant dissociation reaction
      observed. Multiple-stage dissociation experiments suggest that [M - H(2)O +
      Cat](+) is not [b(4) - 1 + Cat](+) arising from the loss of H(2)O from the C
      terminus, but may instead be a species that forms via a mechanism involving the
      elimination of an oxygen atom from an amide group.

PMID- 15170746
TI  - Lipid A components from Pseudomonas aeruginosa PAO1 (serotype O5) and mutant
      strains investigated by electrospray ionization ion-trap mass spectrometry.
AB  - The lipid A components of the Pseudomonas aeruginosa strains PAO1 (wild-type) and
      derived mutants PAO1 algC::tet and PAO1 PDO100 were isolated after mild acetic
      acid hydrolysis of LPS. Their structural heterogeneities were characterized using
      electrospray ionization (ESI) ion-trap mass spectrometry (MS) with direct
      infusion in the negative ion mode without prior derivatization. The ESI-mass
      spectra revealed monophosphorylated molecules corresponding to known tetra-,
      penta- and hexaacylated structures of P. aeruginosa lipid A. The MS/MS
      fragmentation patterns allowed the location of fatty acyl chains on the
      disaccharide backbone of lipid A. In addition, a hexaacylated lipid A containing
      a hexadecanoyl chain was detected for the first time in strain P. aeruginosa
      PAO1. With multiple stages of fragmentation (MS(n)), the position of this
      hexadecanoyl chain O-linked to the decanoyl chain at the C-3(') position of the
      glucosamine backbone was determined. This sensitive method is suitable to reveal
      lipid A heterogeneity, i.e. the nature, number and distribution of acyl chains,
      without prior lipopolysaccharide purification. The lipid A from mutant strains
      were also characterized and significant differences were shown in the abundance
      of monophosphorylated lipid A components between the wild-type and the mutant
      strains.

PMID- 15170747
TI  - Structural analysis of lipid A from Escherichia coli O157:H7:K- using thin-layer
      chromatography and ion-trap mass spectrometry.
AB  - Rapid separation and structural identification of lipid A from Escherichia coli
      were performed using thin-layer chromatography (TLC) and mass spectrometry (MS).
      After the resolved spot of the lipid A had been scraped from TLC plate, the
      sample was re-extracted from the removed powder with chloroform-methanol (2 : 1,
      v/v) and analyzed by matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) and electrospray ionization (ESI) ion-trap MS. For detailed
      structural characterization, multiple-stage mass analysis (MS(4)) of the major
      species in ESI-MS/MS provided important information about the series of fragment
      ions. The dominant fragment ions in each MS stage were produced from the loss of
      fatty acyl groups mainly driven by charge-remote processes, and this information
      about the fragment ions can be used to deduce the composition or the position of
      the fatty acid substituent in the lipid A. In contrast, MALDI-TOFMS indicated
      that fragmentation resulted from charge-driven processes. Molecular mass
      profiling and fragmentation analysis provides essential information for
      clarifying the detailed structure of the lipid A from E. coli O157:H7:K(-).

PMID- 15170748
TI  - Simultaneous determination of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9
      tetrahydrocannabinol and 11-nor-9-carboxy- Delta9-tetrahydrocannabinol in human
      plasma by high-performance liquid chromatography/tandem mass spectrometry.
AB  - A rapid and sensitive method for the simultaneous confirmatory analysis of three
      forensic most relevant cannabinoids, Delta(9)-tetrahydrocannabinol (THC), 11
      hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)
      tetrahydrocannabinol (THC-COOH), by means of high-performance liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) in human plasma was developed
      and fully validated. Sample clean-up was performed by automated silica-based
      solid-phase extraction and the separation was carried out using a PhenylHexyl
      column (50 x 2 mm i.d., 3 micro m) and acetonitrile-5 mM ammonium acetate
      gradient elution. Data were acquired with an API 3000 LC/MS/MS system equipped
      with a turboionspray interface and triple quadrupole mass analyzer using positive
      electrospray ionization and multiple reaction monitoring. Two MS/MS transitions
      for each substance were monitored and deuterated analogues of analytes were used
      as internal standards for quantitation. The limit of quantitation was 0.8 ng ml(
      1) for THC, 0.8 ng ml(-1) for 11-OH-THC and 4.3 ng ml(-1) for THC-COOH and
      linearity with a correlation coefficient r(2) = 0.999 was achieved up to 100 ng
      ml(-1) for THC and 11-OH-THC and 500 ng ml(-1) for THC-COOH. The limits of
      detection were 0.2 ng ml(-1) for THC, 0.2 ng ml(-1) for 11-OH-THC and 1.6 ng ml(
      1) for THC-COOH. The developed LC/MS/MS method was also successfully used for the
      determination of THC-COOH-glucuronide, the phase II metabolite of THC-COOH.

PMID- 15170749
TI  - Simultaneous quantitative analysis of isobars by tandem mass spectrometry from
      unresolved chromatographic peaks.
AB  - A method was developed for the simultaneous quantitation of isobars from
      unresolved chromatographic peaks. The method is based on differences in branching
      ratios of ion abundances in their tandem mass spectra and an assumption that the
      product ion mass spectra of a mixture can be considered as a linear combination
      of the spectra of individual constituents. We present analytical equations and a
      matrix-based approach for deconvoluting the concentration of individual
      components from the total peak intensity for two and three isobars and also a
      matrix-based generalization to any number of compounds. The feasibility of the
      simultaneous analysis of mixtures containing two compounds was assessed. The
      approach was evaluated for the analysis of structural isomers of methylmalonic
      and succinic acids in human plasma and urine samples for a group of 270 samples.
      The linear regression equation, standard error and correlation coefficient for
      the agreement with a traditional method utilizing chromatographic separation of
      the isomers were y = 0.999x - 0.005, 0.024 micro mol l(-1), and 0.985,
      respectively. The utility of a spectral contrast angle as a predictor of analysis
      feasibility was evaluated.

PMID- 15170750
TI  - Mass spectrometry of bisquinolizidine alkaloids: 2- and 17-cyano-substituted
      derivatives of sparteine and lupanine.
AB  - The mass spectral fragmentations of 2-cyano-2-methylsparteine (1), 2-cyano-2
      phenylsparteine (2), 2-cyano-2-(p-tolyl)sparteine (3), 17-cyanosparteine (4) and
      17-cyanolupanine (5) were investigated. Fragmentation pathways, whose
      identification was assisted by accurate mass measurements and a correlation
      between the abundances of the M(+*) and the selected fragment ions of the
      investigated compounds, are discussed. The data obtained create the basis for
      distinguishing the structural metamers.

PMID- 15170752
TI  - Dissociation of ionized benzophenones investigated by the kinetic method:
      effective temperature, steric effects and gas-phase CO+* affinities of phenyl
      radicals.
AB  - Ionized benzophenones ([PhC(O)PhY](+*); Y = 4 - NO(2), 4 - CF(3), 4-F, 4-Br, 4
      Me, 3,4-diMe, 4-OH, 4-OMe, 2-Cl, 2-Me, 2-OH, 2,6-diMe) undergo competitive
      dissociation upon collision-induced dissociation (CID) at 20 eV collision energy
      to generate benzoyl cations ([PhCO](+) and [YPhCO](+)) and phenyl radicals (Ph(*)
      and YPh(*)). For the para-substituted benzophenones, the natural logarithm of the
      abundance ratio of the benzoyl cations [ln([PhCO(+)]/[YPhCO(+)])] is found to
      correlate linearly with the calculated CO(+*) affinities of the phenyl radicals
      Ph(*) and YPh(*). A deviation from linearity is observed for the ortho
      substituted isomers. This is probably due to a significant intramolecular steric
      interaction between the carbonyl group and the ortho substituent which prevents
      the formation of a stable planar system. An observed shift in the intercept
      relative to the origin is interpreted as the result of a systematic error in the
      calculated CO(+*) affinities and this effect is minimized by calculations at a
      higher level. The dissociation of ionized para-substituted benzophenones is
      associated with a relatively high effective temperature of 1816 +/- 41 K,
      calculated from the slope of the kinetic method plot, a value that is consistent
      with a covalent bond in the activated ion. In addition, Delta(DeltaS(CO(+) )),
      the dissociation entropy of the benzoyl cations to form CO(+*) and the aryl
      radical, is found to be about 4 J mol(-1) K(-1) by employing the extended version
      of the kinetic method.

PMID- 15170751
TI  - Determining sequences and post-translational modifications of novel conotoxins in
      Conus victoriae using cDNA sequencing and mass spectrometry.
AB  - A combination of cDNA cloning and detailed mass spectrometric analyses was
      employed to identify novel conotoxins from Conus victoriae. Eleven conotoxin
      sequences were determined using molecular methods: one belonging to the A
      superfamily (Vc1.1), six belonging to the O superfamily (Vc6.1-Vc6.6) and four
      members of the T superfamily (Vc5.1-Vc5.4). In order to verify the sequences and
      identify the post-translational modifications (excluding the disulfide
      connectivity) of three Conus victoriae conotoxins, vc1a, vc5a and vc6a, deduced
      from sequences Vc1.1, Vc5.1, and Vc6.1, respectively, liquid
      chromatography/electrospray ionization ion trap mass spectrometry, matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and
      nanospray ionization ion trap mass spectrometry with collisionally induced
      dissociation were performed on reduced and alkylated venom fractions. We report
      that vc1a, the native form of alpha-conotoxin Vc1.1 (an unmodified 16 amino acid
      residue peptide that has notable pain-relieving capabilities), includes a
      hydroxyproline and a gamma-carboxyglutamate residue. Conotoxin vc5a is a 10
      residue peptide with two disulfide bonds and a hydroxyproline and vc6a is a 25
      amino acid peptide with three disulfide bonds.

PMID- 15170753
TI  - Current literature in mass spectrometry.

PMID- 15170754
TI  - Scanning electron microscopy of the tongue papillae in the pig (Sus scrofa).
AB  - A clear understanding of the role of different papillae in the pig may permit the
      development of a more palatable diet, thus, better utilizing anatomical
      structures and morphological characteristics to enhance health and productivity
      in this domestic species. The study used ten healthy market-size, mixed-breed
      pigs to properly describe the surface structure of the tongue papillae using
      standard scanning electron microscopic techniques. Two types of sharp and blunt
      filiform papillae were identified. Fungiform papillae, located on the lateral
      side of the tongue, were circular and large with surface taste pores. The
      majority of oval papillae on the dorsal surface of the tongue contained
      multidirectional surface grooves and lacked taste pores. The foliate papillae,
      located principally on the caudal third and lateral part of the tongue, were
      comprised of four to five leaves and they had additional pseudopapillae. The two
      vallate papillae, found in the caudal third and dorsum of the tongue, had a well
      defined vallum and pseudopapillae on their surface. At the root of the tongue,
      two types of conical papillae with or without apex were observed. The entire area
      covered by conical papillae was deeply occupied by lingual tonsils. The lingual
      tonsils were scattered with varying sized lymph nodules in the propria mucosa of
      the conical papillae deep to epithelium. Functionally, the filiform and conical
      papillae appeared to have a mechanical role whereas fungiform, foliate, and
      vallate papillae apparently perform a gustatory role in the pig. The tonsillar
      location at the root of the tongue provides an ideal experimental model for
      immunohistological and immunological studies on the lymphoid tissue in man.

PMID- 15170755
TI  - Nanoporous aluminum oxide affects neutrophil behaviour.
AB  - This study evaluates neutrophil responses on aluminum oxide membranes. Using an
      in vitro cell culture system, we have found that the pore size (20 and 200 nm in
      diameter) of alumina membranes have a significant effect on leukocyte morphology
      and activation. Specifically, our results show that 20-nm pore-size membranes
      were more potent in triggering PMN spreading and extending of pseudopodia than
      200-nm pore-size membranes. The morphological changes are also associated with
      cell activation. In fact, adherent neutrophils on 20-nm pore-size membranes
      elicit much stronger initial oxygen free radical production. Overall, our results
      point out that membrane pore size significantly affects the extent of cellular
      responses of adherent neutrophils.

PMID- 15170756
TI  - Antennal sensilla of two parasitoid wasps: a comparative scanning electron
      microscopy study.
AB  - Two closely related parasitoid wasp species, Cotesia glomerata (L.) and Cotesia
      rubecula (Marshall) (Hymenoptera:Braconidae), are different in their associative
      learning of plant odors. To provide a solid basis for our research on the
      mechanisms that underlie this difference, we described the morphology of the
      antennal sensilla of these two species using scanning electron microscopy
      complemented with transmission electron microscopy. Female and male antennae of
      both species have the same six types of sensilla. We classified these sensilla as
      sensilla trichodea without pores, sensilla trichodea with a tip pore, sensilla
      trichodea with wall pores, sensilla coeloconica type I, sensilla coeloconica type
      II, and sensilla placodea. We conclude that the morphology, numbers, and
      distribution of the sensory receptors are highly similar in these two closely
      related wasp species. Differences between species and sexes occurred only in
      sensilla placodea numbers. C. rubecula has more sensilla placodea than C.
      glomerata and males of both species have a larger number and a higher density of
      sensilla placodea compared to females of the same species.

PMID- 15170757
TI  - Effect of streptozotocin on the ultrastructure of rat pancreatic islets.
AB  - Our objective was to study the effects of three (30, 40, and 50 mg/kg) doses of
      Streptozotocin (STZ) on fasting plasma glucose level (FPG) and observe its
      effects at the cellular level in rat pancreas by electron microscopy. FPG was
      measured in rats before induction of diabetes and then on 3, 7, and 14 days after
      induction of diabetes with STZ. Keto diastix urine strips were used to check
      urine glucose and ketone bodies. Two weeks after the induction of diabetes, the
      rat pancreas was removed and fixed for light and electron microscopic studies.
      Three days after induction, the mean FPG level was 112 mg/dl in Group I (30 mg/kg
      STZ), 217 mg/dl in Group II (40 mg/kg STZ), and 376 mg/dl in Group III (50 mg/kg
      STZ). Histology was normal in Group I but revealed altered islet structure in
      Groups II and III. Ultrastructure revealed intact D cells in all three groups.
      The focal mitochondria and Golgi complex swelling found in A and B cells was
      occasional in Group I and frequent in Groups II and III. Swelling of other
      organelles and reduction in the size and number of granules was further observed
      in Group III. It is our conclusion that the 30-mg/kg body weight STZ produces
      mild changes while 50 mg/kg proves to be fatal. STZ at 40 mg/kg has a moderate
      effect on plasma glucose as well as on the islets of Langerhans at a cellular
      level.

PMID- 15170758
TI  - Fluorescence shell: a novel view of sclereid morphology with the Confocal Laser
      Scanning Microscope.
AB  - Confocal Laser Scanning Microscopy (CLSM) was used to observe sclereids from
      stems of Avicennia germinans and from fruits of two species of pear (Pyrus
      calleryana "Bradford" and P. communis "Red Bartlett"). The images obtained from
      thick (25 to 100 microm) free-hand sections were, in certain respects, far
      superior to those obtained by other, more invasive and time-consuming microscopic
      techniques upon which previous reports of sclereid morphology were based. The
      cell wall surfaces, including the "internal" surfaces of the branched pit canals
      and cell lumens, were much accentuated with the techniques we describe, resulting
      in a "fluorescence shell" image, meaning the cell wall did not stain all the way
      through but instead only at the inner and outer wall surfaces, including the
      edges of ramiform pits. By controlling the time of staining with 1% aqueous
      Safranin O, or by changing the number of optical sections used in extended focus
      images, it was possible to get either a conventional view of the cell wall
      structure or a unique, three-dimensional view of the elaborate cell
      interconnections. Similar fluorescence shell images of sclereids were also
      obtained using a periodic-Schiff (PAS) staining system, but the stain was not as
      specific to sclereid cell walls as was the Safranin O stain. Particularly with
      the use of a narrow range band pass emission filter of 505-530 nm, the Safranin O
      staining may be more specific to lignin than reported in the literature.

PMID- 15170759
TI  - An EBSP study of isothermally-annealed cold-rolled nickel.
AB  - Scanning electron microscopy and electron backscattered patterns, EBSP, have been
      employed to reveal both the grain structure and texture of 90% cold-rolled
      polycrystalline nickel after 1-hour anneals at a variety of temperatures. After
      annealing at either 400 degrees or 500 degrees C, small, cube-oriented, equi-axed
      grains were produced via primary recrystallization. At 600 degrees C, large
      [124]<211> oriented grains accounted for an increasing proportion of the
      microstructure, until at 1000 degrees C only large grains ( approximately 600
      microm) and a sharp [124]<211> texture were present. Detailed EBSP analyses of
      the grain boundaries surrounding the large abnormally grown grains observed at
      600 degrees C demonstrated that formation of the secondary recrystallization
      texture was due to migration of high-mobility, random high-angle boundaries
      around grains that had a size advantage, consistent with the Abbruzzese-Lucke
      model.

PMID- 15170760
TI  - Electron energy loss spectroscopy for analysis of inhaled ultrafine particles in
      rat lungs.
AB  - Epidemiologic studies have associated cardiovascular morbidity and mortality with
      ambient particulate air pollution. Particles smaller than 100 nm in diameter
      (ultrafine particles) are present in the urban atmosphere in very high numbers
      yet at very low mass concentration. Organs beyond the lungs are considered as
      targets for inhaled ultrafine particles, whereby the route of particle
      translocation deeper into the lungs is unclear. Five rats were exposed to
      aerosols of ultrafine titanium dioxide particles of a count median diameter of 22
      nm (geometric standard deviation, GSD 1.7) for 1 hour. The lungs were fixed by
      intravascular perfusion of fixatives immediately thereafter. TiO(2) particles in
      probes of the aerosol as well as in systematic tissue samples were analyzed with
      a LEO 912 transmission electron microscope equipped with an energy filter for
      elemental microanalysis. The characteristic energy loss spectra were obtained by
      fast spectrum acquisition. Aerosol particles as well as those in the lung tissue
      were unambiguously identified by electron energy loss spectroscopy. Particles
      were mainly found as small clusters with a rounded shape. Seven percent of the
      particles in the lung tissue had a needle-like shape. The size distribution of
      the cluster profiles in the tissue had a count median diameter of 29 nm (GSD
      1.7), which indicates no severe clustering or reshaping of the originally inhaled
      particles. Electron energy loss spectroscopy and related analytical methods were
      found to be suitable to identify and localize ultrafine titanium dioxide
      particles within chemically fixed and resin-embedded lung tissue.

PMID- 15170761
TI  - Technical note: A toy as tool: a low-cost image analysis system for the
      evaluation of tumor size in experimental small animal models.
AB  - Image analysis systems are an essential tool in measurements of size of
      intraparenchymal tumors or lesions in experimental small animal models.
      Conventional image analysis systems are relatively expensive. We therefore
      compared the performance of a professional image analysis system with an
      inexpensive setup by evaluating tumor size in an orthotopic glioma mouse model.
      The maximum cross-sectional tumor area of H&E stained brain-slides of two groups
      of mice (treatment and control group) was measured by two independent
      investigators using a professional image analysis system (Leica DM IRB
      microscope) with the Leica Quantimet 500c software, and a low-cost-system (Intel
      QX3 microscope) with a non-commercial image analysis software. Mean tumor volumes
      were calculated and the results from each of the image analysis systems,
      investigators, and treatment effects were compared. The tumor volumes as measured
      with the low-cost and the professional system differed between -3.7 and +7.5% (P
      = 0.69-0.99). Measurements made by investigator A and B differed between -7.0 and
      +3.9% (P = 0.69-0.88). Treatment in all cases significantly reduced the tumor
      volume between 58.4 and 62.7% (P = 0.0002 or 0.0003), regardless of the
      investigator or the used image analysis system. We therefore conclude that the
      QX3 low-cost microscope in combination with a non-commercial image-analysis
      software represents an inexpensive solution to reliably analyze the size of
      regions of interest, if they provide a sufficient contrast. However, the low-cost
      setup due to its low resolution definitely limits a detailed analysis of
      histologic features.

PMID- 15170762
TI  - High frequency of use of rofecoxib at greater than recommended doses: cause for
      concern.
AB  - PURPOSE: To determine the prevalence of chronic use of rofecoxib 50 mg. Rofecoxib
      is unusual among nonsteroidal anti-inflammatory drugs (NSAIDs) in that the
      licensed dose for acute pain is double the maximum dose recommended for chronic
      use. The 50 mg dose is recommended for acute pain only, for a maximum of 5 days.
      In clinical trials of chronic use for arthritis, hypertension was more frequent
      in patients assigned 50 mg rofecoxib than in those assigned lower doses or other
      NSAIDs. Thus chronic use of high doses of rofecoxib has implications for patient
      safety. METHODS: Cross-sectional analysis of the prevalence of chronic use of
      rofecoxib 50 mg in 2001, among persons aged > or =50 years, enrolled in the
      Tennessee Medicaid program. RESULTS: On 1 July 2001, 14% of the study population
      had a current prescription for an NSAID, with a supply of pills for >5 days. Of
      all NSAID prescriptions, 25% were for rofecoxib, and 17% of these prescriptions
      were for >25 mg daily. Of those prescribed >25 mg daily, 71% filled prescriptions
      for at least 50 mg for 30 days. In this latter group, 60% and 69% filled another
      rofecoxib prescription within 1 and 2 weeks, respectively, of the end of their 30
      days supply. Demographics and co-morbid conditions of high dose rofecoxib users
      did not differ substantially from users of other NSAIDs or the total population.
      CONCLUSION: Use of rofecoxib 50 mg for >5 days is relatively common. In view of
      dose-related adverse effects, such use should be discouraged.

PMID- 15170763
TI  - Application of a propensity score to adjust for channelling bias with NSAIDs.
AB  - PURPOSE: To compare the relative risks of upper GI haemorrhage (UGIH) in users of
      Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by
      regression on individual covariates, a propensity score and both. METHODS: Cohort
      study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure
      to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated
      for each patient. Results of multiple covariate analyses and the propensity
      scoring technique to assess potential channelling bias in comparisons between
      Newer and Older non-specific NSAIDs were compared. RESULTS: This study included
      7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to
      coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving
      Newer NSAIDs were older, more likely to have a history of GI symptoms, and at
      higher risk for GI complications. Adjusting for these risk factors reduced the
      relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs
      to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively. CONCLUSIONS:
      Channelling towards high GI risk patients occurred in the prescribing of Newer
      NSAIDs. Propensity scores highlighted the markedly different risk profiles of
      users of Newer and Older non-specific NSAID. Correcting for channelling bias,
      coxib exposure, but not meloxicam exposure, was associated with less UGIH than
      Older non-specific NSAID exposure. In the present study, corrections made by
      regression on a propensity score and on individual covariates were similar.

PMID- 15170764
TI  - Introducing triage logic as a new strategy for the detection of signals in the
      WHO Drug Monitoring Database.
AB  - PURPOSE: An important role for the WHO Programme for International Drug
      Monitoring is to identify signals of international drug safety problems as early
      as possible. The signal detection strategy, operated at the Uppsala Monitoring
      Centre (UMC), gave too many drug-adverse drug reaction (ADR) combinations for
      individual review. Therefore additional selection strategies were needed to
      improve the likely signal-to-noise ratio and for the UMC to complement the
      efforts of national centres in an efficient way. METHODS: The combinations
      database of the first quarter of 2001 was analysed using algorithms representing
      different strategies for finding relevant signals using triage logic. RESULTS:
      The strategies that together gave a manageable number of combinations, i.e.
      around 600, for further consideration in a single quarter were the algorithms for
      'Rapid reporting increase', 'Serious reaction and new drug' and 'Special
      interests'. These filters began to be used routinely on the combinations database
      in late 2001. CONCLUSIONS: While stressing that human review is essential, triage
      strategies are useful when attempting analysis of large amounts of data. By
      definition, the use of triage strategies may exclude some potential signals from
      consideration, although the intention is to improve the chances of detection by
      focussing on areas of greatest importance.

PMID- 15170765
TI  - Refill rate of antipsychotic drugs: an easy and inexpensive method to monitor
      patients' compliance by using computerised pharmacy data.
AB  - PURPOSE: In the literature, noncompliance to medication in patients with
      schizophrenia ranges from 20 to 89%. There is an urgent need for reliable and
      valid techniques that measure compliance in antipsychotic drug treatment. In this
      study, we use pharmacy-dispensing records to assess compliance by calculating the
      refill rate of antipsychotic medication. METHODS: Refill rates of chronic
      antipsychotic drug users in 1999 and in 2000 were established by dividing the
      number of prescribed days by the total number of calendar days that the patient
      was registered in a pharmacy prescription records database. RESULTS: More than
      50% of patients using an antipsychotic drug show a refill rate that is associated
      with medication compliance (0.9-1.1). The number of daily antipsychotic drug
      intakes was associated with a divergent refill rate, more than once daily dosing
      was associated with a significantly elevated refill rate (p < 0.015).
      CONCLUSIONS: The refill rate is a valuable addition to the small arsenal of
      objective compliance measurement tools. It is an easy to obtain and inexpensive
      way to estimate (non)compliance. We recommend future studies to medication use in
      both mental and physical disorders, in order to further specify the actual value
      of refill rates in clinical practice.

PMID- 15170766
TI  - Use of herbal drugs in pregnancy: a survey among 400 Norwegian women.
AB  - PURPOSE: To investigate the use of herbal drugs by pregnant women. METHODS: We
      interviewed 400 postpartum women at Ulleval University Hospital in Oslo, Norway
      about the use of herbal drugs, within 3 days after giving birth by using a
      structured questionnaire in the period from February to June 2001. RESULTS: We
      found that 36% of the pregnant women had used herbal drugs during pregnancy with
      an average of 1.7 products per woman. The proportion of women using herbal drugs
      increased throughout the first, second and third pregnancy trimester. The most
      commonly used herbs were echinacea, iron-rich herbs, ginger, chamomile and
      cranberry. Among the women having used herbal drugs in pregnancy, 39% had used
      herbal drugs that were considered possibly harmful or herbs where information
      about safety in pregnancy was missing. Herbal galactagogues had been used by 43%
      of the women who had breastfed a prior child during their breast-feeding period.
      Use of herbal drugs in pregnancy had most commonly been recommended by family or
      friends. CONCLUSION: The widespread use of herbal drugs during pregnancy
      indicates an increased need for documentation about the safety of herbal drugs in
      pregnancy. To meet the needs of pregnant women, it is necessary for health care
      personnel to have knowledge about herbal drugs during pregnancy.

PMID- 15170767
TI  - Pharmacoepidemiology 101: data monitoring committees in the post-marketing
      approval setting.
AB  - The development of the risk management paradigm for the enhancement of post
      marketing approval drug safety carries with it the need for external monitoring
      of the different approaches used by the sponsor. The concept of a Data Monitoring
      Committee (DMC), widely used in the management of randomized clinical trials, is
      adapted to provide this monitoring function. The rationale for the post-marketing
      approval DMC is considered in the context of the risk management paradigm, as
      well as in the more traditional post-marketing approval surveillance setting. The
      composition and operation of the post-marketing approval DMC are considered, as
      well as the process of implementing the committee. Although the adaptation
      proposed in this article is focused on the paradigm proposed by the United States
      Food and Drug Administration, it is likely that it will require modification as
      risk management is adopted (and adapted) by other health regulators.

PMID- 15170768
TI  - Comparison of data mining methodologies using Japanese spontaneous reports.
AB  - PURPOSE: Five data mining methodologies for detecting a possible signal from
      spontaneous reports on adverse drug reactions (ADRs) were compared. METHODS: The
      five methodologies, the Bayesian method using the Gamma Poissson Shrinker (GPS),
      the method employed in the UK Medicines Control Agency (MCA), the Bayesian
      Confidence Propagation Neural Network (BCPNN), the method using the 95%
      confidence interval (CI) for the reporting odds ratio (RORCI) and that using the
      95% CI of the proportional reporting ratio (PRRCI) were compared using Japanese
      data obtained between 1998 and 2000. RESULTS: There were all in all 38,731 drug
      ADR combinations. The count of drug-ADR pairs was equal to 1 or 2 for 31,230
      combinations and none of them were identified as a possible signal with the MCA
      or BCPNN. Similarly, the GPS detected a possible signal in none of the
      combinations where the count was equal to 1 but in 7.5% of the combinations where
      the count was equal to 2. The RORCI and PRRCI detected a possible signal in more
      than half of the combinations where the count was equal to 1 or 2. When the
      pairwise agreement on whether or not a drug-ADR combination satisfied the
      criteria for a possible signal was assessed for the 38,731 combinations, the
      concordance measure kappa was greater than 0.9 between the MCA and BCPNN and
      between the RORCI and PRRCI. Kappa was around 0.6 between the GPS and MCA and
      between the GPS and BCPNN. Otherwise, kappa was smaller than 0.2. CONCLUSIONS:
      The drug-ADR combinations detected as a possible signal vary between different
      methodologies.

PMID- 15170769
TI  - Correlated measures in longitudinal analysis of daily drug use patterns in a
      general intensive care unit.
AB  - PURPOSE: The objective of the present study is to compare two different study
      designs (with and without corrections for correlated measures) to identify
      possible determinants of psychotropic drug use in an intensive care unit (ICU).
      METHODS: In a logistic regression analysis, odds ratios (OR) were calculated for
      days in which patients were exposed to psychotropics compared with non-exposed
      days. In order to adjust for correlated measures, logistic regression with a
      logistic binomial model was applied. RESULTS: We found that adjustment for
      correlated measures did not result in major changes in the OR. However, with more
      observations per patient parameter, adjustment for correlation has greater
      effect. CONCLUSIONS: Adjustment for correlated measures may be useful in
      longitudinal drug analyses.

PMID- 15170770
TI  - Psychosocial factors at the workplace--do they affect substance use? Evidence
      from the Tyrolean workplace study.
AB  - BACKGROUND: To determine the prevalence of drug consumption and the impact of
      workplace demands and burdens for substance use, we conducted a survey in a
      representative sample of Tyrolean employees. METHODS: This analysis was
      restricted to the 700 respondents (395 male, 305 female; age 18-60 years) in the
      year 2001 by telephone interview who hold a full-time or part-time job during the
      6 months preceding the interview. We studied the use of antidepressants,
      benzodiazepines, analgetics. stimulants and phytotherapeutics. RESULTS: Of the
      whole sample, 5.6% employees (4.8% male, 6.6% female) stated that they take some
      kind of pills to cope with job demands. There was no statistically significant
      difference between males and females. Substance use depended to a great extent on
      the work atmosphere and job satisfaction. The prevalence of drug consumption
      increased from 3.7% (good atmosphere at work) and 3.3% (high job satisfaction) to
      12.6% (bad atmosphere at work) and 42.9% (low job satisfaction ) (p = 0.019 and p
      = 0.001). The feeling of being a victim of bullying at work appears to be
      particularly destructive for the individuals' well-being. Only 4.1% of the
      employees who were not victims of bullying took drugs because of job problems, as
      compared with 20% of the bullying victims. DISCUSSION: Our results indicate that
      drug consumption as the consequence of workplace burdens is a frequent and
      serious problem with negative consequences for the life quality of the
      individuals and for the individuals' efficiency. Therefore, occupational medicine
      and employers should direct their attention to ensure the best possible work
      place structure and occupational conditions.

PMID- 15170771
TI  - Factors related with prescription requirement to dispense in Spain.
AB  - PURPOSE: To identify factors associated with prescription requirement to
      dispense. METHODS: We carried out a cross-sectional study on a sample of 166
      pharmacists in North-West Spain. The following independent variables were
      collected through a personal interview: pharmacist's education and speciality,
      characteristics of the pharmacy, and its socio-economic environment. We
      constructed multiple regression models using as dependent variables: requirement
      of prescription to dispense five drugs which have to be dispensed with a
      prescription; and opinion on whether a prescription should be required to
      dispense these drugs. RESULTS: The response rate was 98.8%. A proportion of 65.9%
      of pharmacists dispense antibiotics without any prescription. This proportion is
      83.5% for nonsteroidal anti-inflammatory drugs, 46.3% for ACE inhibitors, 13.4%
      for benzodiazepines and 84.8% for oral contraceptives. A higher requirement
      prescription was found to be associated with the antecedent of a speciality
      training of the pharmacist (p = 0.028) and his or her age (p < 0.001). A low
      prescription requirement is associated with the condition of being owner of the
      pharmacy (p = 0.032), with a high economic level of the population attended (p =
      0.016) and with the size of the pharmacy (p = 0.045). CONCLUSIONS: The proportion
      of pharmacists who dispense drugs without a prescription is extremely high. Our
      results suggest that in order to increase quality of dispensing, it is necessary
      to increase pharmacist education and direct efforts of awareness primarily at
      pharmacists in charge, who are young and work in large pharmacies.

PMID- 15170772
TI  - Initial uptake and evidence of safe prescribing practice with Buproprion (Zyban).
AB  - PURPOSE: To study the effect of safety concerns and the introduction of freely
      available nicotine replacement therapy (NRT) on the prescribing of Buproprion
      within the General Medical Services (GMS) scheme in Ireland. METHODS: Using the
      state-supported GMS prescription database in Ireland, we identified 8166 patients
      who were prescribed Buproprion and 18,450 patients who were prescribed NRT over a
      12-month-period. RESULTS: A decline in the prescribing of Buproprion was noted
      which coincided with concerns regarding the safety of the drug but which preceded
      the introduction of NRT to the GMS. Furthermore, patients who were prescribed
      Buproprion were less likely to be co-prescribed potentially interacting drugs
      (odds ratio (OR): 0.48, 95% confidence intervals (CI): 0.42, 0.54) or drugs known
      to reduce seizure threshold (OR: 0.63, 95% CI: 0.6, 0.67) indicating good
      prescribing practice. Patients aged 65 years or more were less likely to be
      prescribed any form of smoking cessation therapy compared with those aged <65
      years (OR: 0.23, 95% CI: 0.22-0.24) indicating that such therapy was targeted at
      those most likely to benefit. CONCLUSIONS: We provide evidence that prescribers
      exercised caution in the prescription of Buproprion and were likely to have been
      influenced both by the safety concerns and the introduction of freely available
      NRT to the GMS population.

PMID- 15170775
TI  - MR and CT assessment for ischemic cardiac disease.
AB  - Magnetic resonance imaging and/or contrast-enhanced multidetector computed
      tomography may be used separately or, often more effectively, in an integrated
      fashion, to address important issues in patients with coronary artery disease
      causing ischemic cardiac disease (ICD). These issues include complications of
      myocardial infarction, such as ventricular dysfunction, myocardial wall rupture,
      aneurysm formation, intracavitary thrombus, mitral insufficiency, and
      pericarditis, as well as aspects of planning and monitoring therapy for ICD, such
      as revascularization and ventricular aneurysm repair.

PMID- 15170776
TI  - Past, present, and future perspective of cardiac computed tomography.
AB  - In the United States, more than 1 million diagnostic invasive coronary angiograms
      are performed annually, and in about 50% the investigation is followed by an
      interventional procedure. The remaining symptomatic patients after angiography
      are treated conservatively or by bypass graft surgery. In recent decades coronary
      angiography has advanced to a fast and safe investigation. Nevertheless, in
      particular, patients are well aware of the small but not negligible risk of
      complications and the discomfort of the invasive procedure. In addition to
      electrocardiogram (EKG) or ultrasound stress test and thallium scintigraphy,
      there is further need for another noninvasive method that displays the morphology
      of the coronary arteries in a way that would allow the triage of patients with
      suspicion of coronary artery disease (CAD) for a conservative, interventional, or
      surgical treatment.

PMID- 15170777
TI  - Coronary artery magnetic resonance angiography.
AB  - Coronary magnetic resonance angiography (coronary MRA) continues to advance
      rapidly from both a technical and clinical perspective. Coronary MRA has
      benefited directly from improvements in spatial resolution, contrast definition,
      and advances in motion correction, which have furthered its routine use in
      evaluating coronary artery bypass grafts and anomalous coronary arteries. Work in
      refining the techniques for more accurate identification of coronary artery
      disease (CAD) continues, with advances in navigator-gated and breath-hold motion
      correction techniques, novel k-space strategies (e.g., spiral and radial k-space
      filling), development and application of intravascular contrast agents, and
      imaging at higher field strengths. Ultimately, these developments may lead to the
      routine application of coronary MRA as a screening tool for CAD. This article
      reviews the development of coronary MRA, discusses the requirements and tools
      necessary for optimal visualization of the coronary arteries, and describes the
      application of coronary MRA to acquired and congenital CAD.

PMID- 15170778
TI  - MRI of atherosclerosis.
AB  - The emergence of high-resolution, rapid imaging methods has enabled MRI to
      noninvasively image the fine internal structure of atherosclerotic artery walls.
      This capability has, in turn, captured the interest of clinicians, who see it as
      an opportunity to assess disease severity based on the characteristics of
      atherosclerotic lesions themselves, rather than only their effects on the vessel
      lumen. MRI of atherosclerosis thus has the potential to be used in medical
      treatment decisions or to assess the effects of experimental treatment options.
      Given this potential, a number of research groups have been investigating MRI of
      atherosclerosis in an effort to establish the ability of MRI to determine
      atherosclerotic plaque burden, detect plaque composition, and ultimately identify
      vulnerable plaque before it leads to a clinical event. In this review, the
      current state of the art is summarized for the three primary vessel targets: the
      carotid artery, the aorta, and the coronary arteries.

PMID- 15170779
TI  - Imaging of coronary calcification by computed tomography.
AB  - As an unequivocal biomarker for arteriosclerosis, the presence of coronary
      calcium serves as a qualitative reflection of the severity of coronary artery
      disease (CAD). Greater calcium burdens correlate with more advanced disease, a
      higher likelihood of coronary stenoses, and a higher risk for coronary heart
      disease (CHD). Empirically, the quantification of coronary calcium not only
      provides an accurate reflection of disease severity, but also has great potential
      as a screening tool for CHD. Computed tomography (CT) has been shown to be
      capable of providing accurate, noninvasive measurements of coronary
      calcification. Evidence shows that calcium measurements by CT correlate well with
      histological plaque analyses, and that calcium burdens accurately reflect disease
      severity and can be used to assess individual risk for CHD. The purpose of this
      review article is to examine the accumulated evidence that has attempted to
      validate CT as a diagnostic tool for CAD and as a screening exam for CHD.

PMID- 15170780
TI  - Magnetic resonance imaging-guided coronary interventions.
AB  - Magnetic resonance imaging (MRI) guidance for coronary interventions offers
      potential advantages over conventional x-ray angiography. Advantages include the
      use of nonionizing radiation, combined assessment of anatomy and function, and
      three-dimensional assessment of the coronary arteries leading to the myocardium.
      These advantages have prompted a series of recent studies in this field. Real
      time coronary MR angiography, with low-dose catheter-directed intraarterial (IA)
      infusion of contrast media, has achieved in-plane spatial resolution as low as
      0.8 x 0.8 mm2 and temporal resolution as short as 130 msec per image. Catheter
      based IA injection of contrast agent has proven useful in the collection of
      multislice and three-dimensional images, not only for coronary intervention
      guidance, but also in the assessment of regional myocardial perfusion fed by the
      affected vessel. Actively visible guidewires and guiding catheters, based on the
      loopless antenna concept, have been effectively used to negotiate tortuous
      coronary vessels during catheterization, permitting placement of coronary
      angioplasty balloon catheters. Passive tracking approaches have been used to
      image contrast agent-filled coronary catheters and to place susceptibility-based
      endovascular stents. Although the field is in its infancy, these early results
      demonstrate the feasibility for performing MRI-guided coronary interventions.
      Although further methodological and technical developments are required before
      these methods become clinically applicable, we anticipate that MRI someday will
      be included in the armamentarium of techniques used to diagnose and treat
      coronary artery disease.

PMID- 15170781
TI  - Imaging of myocardial perfusion with magnetic resonance.
AB  - Coronary artery disease (CAD) is currently the leading cause of death in
      developed nations. Reflecting the complexity of cardiac function and morphology,
      noninvasive diagnosis of CAD represents a major challenge for medical imaging.
      Although coronary artery stenoses can be depicted with magnetic resonance (MR)
      and computed tomography (CT) techniques, its functional or hemodynamic impact
      frequently remains elusive. Therefore, there is growing interest in other, target
      organ-specific parameters such as myocardial function at stress and first-pass
      myocardial perfusion imaging to assess myocardial blood flow. This review
      explores the pathophysiologic background, recent technical developments, and
      current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

PMID- 15170782
TI  - Analysis of myocardial perfusion MRI.
AB  - Rapid MR imaging (MRI) during the first pass of an injected tracer is used to
      assess myocardial perfusion with a spatial resolution of 2-3 mm, and to detect
      any regional impairments of myocardial blood flow (MBF) that may lead to
      ischemia. The spatial resolution is sufficient to detect flow reductions that are
      limited to the subendocardial layer. The capacity of the coronary system to
      increase MBF severalfold in response to vasodilation can be quantified by
      analysis of the myocardial contrast enhancement. The myocardial perfusion reserve
      (MPR) is a useful concept for quantifying the vasodilator response. The perfusion
      reserve can be estimated from the ratio of MBFs during vasodilation and at
      baseline, in units identical to those used for invasive measurements with labeled
      microspheres, or from dimensionless flow indices normalized by their value for
      autoregulated flow at rest. The perfusion reserve can be reduced as a result of a
      blunted hyperemic response and/or an abnormal resting blood flow. The absolute
      quantification of MBF removes uncertainties in the evaluation of the vasodilator
      response, and can be achieved without the use of complex tracer kinetic models;
      therefore, its application to clinical studies is feasible.

PMID- 15170784
TI  - MR imaging assessment of cardiac function.
AB  - Magnetic resonance (MR) imaging is an accurate and reproducible technique for
      assessment of ventricular function. Although echocardiography is the mainstay for
      evaluation of cardiac function, dobutamine stress MR imaging has been shown to be
      as safe as echocardiography for patients with coronary artery disease and more
      accurate in patients with suboptimal echocardiographic image quality. This
      article reviews MR imaging techniques, methods of pharmacologic stress, and
      clinical applications for assessment of cardiac function, primarily left
      ventricular function.

PMID- 15170783
TI  - Magnetic resonance imaging for the assessment of myocardial viability.
AB  - The identification of myocardial viability in the setting of left ventricular
      (LV) dysfunction is crucial for the prediction of functional recovery following
      revascularization. Although echocardiography, positron emission tomography (PET),
      and nuclear imaging have validated roles, recent advances in cardiac magnetic
      resonance (CMR) technology and availability have led to increased experience in
      CMR for identification of myocardial viability. CMR has unique advantages in the
      ability of magnetic resonance spectroscopy (MRS) to measure subcellular
      components of myocardium, and in the image resolution of magnetic resonance
      proton imaging. As a result of excellent image resolution and advances in pulse
      sequences and coil technology, magnetic resonance imaging (MRI) can be used to
      identify the transmural extent of myocardial infarction (MI) in vivo for the
      first time. This review of the role of CMR in myocardial viability imaging
      describes the acute and chronic settings of ventricular dysfunction and concepts
      regarding the underlying pathophysiology. Recent advances in MRS and MRI are
      discussed, including the potential for dobutamine MRI to identify viable
      myocardium and a detailed review of the technique of delayed gadolinium (Gd)
      contrast hyperenhancement for visualization of viable and nonviable myocardium.

PMID- 15170785
TI  - Computed tomography assessment of myocardial perfusion, viability, and function.
AB  - In addition to coronary artery assessment, contrast-enhanced multidetector spiral
      computed tomography (CE-MDCT) can provide valuable information about myocardial
      perfusion. Using CE-MDCT, myocardial perfusion defects are often observed in the
      early phase of the contrast bolus (early defect (ED)), with residual defects
      (RDs) and late enhancement (LE) observed in the late phase in myocardial
      infarction (MI). However, the clinical significance of EDs, RDs, and LE has not
      yet been fully described. This work reviews myocardial viability and function by
      CE-MDCT based on our prior data by including contrast-enhanced single-slice
      (detector) CT (CE-SSCT) and CE-MDCT. Recently, equivalent results were obtained,
      as seen in CE-SSCT with images by CE-MDCT. In this review, images that were
      acquired by MDCT will be presented. In this work, the following items will be the
      focus: myocardial enhancement patterns (EDs, LE, and RDs), early perfusion
      defects and their relationship to wall thickness (WT) and wall motion, early CT
      perfusion defects vs. Tl-201 single photon emission CT (SPECT), the protocol for
      performing dual-phase contrast CT, classification of enhancement patterns,
      enhancement patterns on dual-phase CE-MDCT vs. left ventricular functional
      recovery and WT, changes in enhancement patterns in conjunction with healing
      stage, enhancement patterns on dual-phase CE-MDCT vs. 201Tl/99mTc-pyrophosphate
      (dual-isotope SPECT), the clinical meaning of each enhancement pattern, pitfalls
      of enhancement patterns and other diseases, and study limitations and the future
      of MDCT.

PMID- 15170786
TI  - Assessment of pericardial disease by magnetic resonance and computed tomography.
AB  - Pericardial disease and its consequences can be well shown with magnetic
      resonance imaging (MRI) and computed tomography (CT). Here I review the normal
      and pathologic anatomy and physiology of the pericardium, approaches to MRI and
      CT imaging of the pericardium, and some specific considerations in common
      conditions affecting the pericardium.

PMID- 15170787
TI  - Magnetic resonance and computed tomographic evaluation of congenital heart
      disease.
AB  - Magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT)
      provide noninvasive visualization of morphologic changes in pediatric and adult
      patients with congenital heart disease, as well as the functional changes caused
      by the underlying morphologic abnormalities. Clinical experience with MRI is
      richer than that with fast CT, but CT appears to provide accurate and high
      quality imagery for diagnosis. The two modalities may be complementary. That is,
      intracardiac anatomy is so well depicted by MRI, and CT provides exquisite images
      of the great vessels. Furthermore, in adult patients, MR and CT are helpful in
      demonstrating and quantitating physiologic changes superimposed by acquired
      cardiovascular disease on the underlying congenital malformations. Using MRI,
      spin echo acquisitions provide the image data for evaluation of morphologic
      changes, and gradient reversal techniques add functional and flow data to
      complement morphologic changes. Contrast-enhanced electrocardiographic (ECG)
      gated multidetector and electron beam CT examination provide morphologic
      information and may be used as a data set for off-line functional quantitation.

PMID- 15170788
TI  - Magnetic resonance and computed tomography imaging of arrhythmogenic right
      ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a familial cardiomyopathy
      that causes fibro-fatty replacement of the right ventricle (RV), leading to
      sudden death due to ventricular arrhythmias. The disease is an important cause of
      sudden death in individuals younger than 35 years of age. Structural and
      functional abnormalities of the RV constitute an important diagnostic criterion
      for the disease. Diagnosis of ARVD is often a challenge as conventional imaging
      modalities have significant limitations to visualize the RV. Recently, magnetic
      resonance imaging (MRI) and computed tomographic (CT) imaging have emerged as
      robust clinical tools for evaluation of myocardial pathology. In addition to
      providing morphologic and functional information, both imaging modalities have
      the ability to demonstrate intramyocardial fat, which is the pathological
      hallmark in ARVD. This article discusses the current status and role of MRI and
      CT imaging in the diagnosis of ARVD.

PMID- 15170789
TI  - Radiation dose in multidetector row computed tomography cardiac imaging.
AB  - Multidetector row computed tomography (MDCT) with its markedly improved temporal
      and spatial resolution has opened up a new opportunity in cardiac CT imaging.
      MDCT scanners are increasingly available and have become the preferred CT
      scanners for the entire spectrum of clinical CT examinations. As a consequence,
      the number of cardiac CT studies is continuously growing. Because cardiac CT
      studies involve considerable radiation doses, it is compelling for us to
      understand the radiation dose estimates associated with cardiac CT imaging. In
      this article, we review the concepts of radiation dose measurement in CT, discuss
      MDCT scan parameters affecting radiation exposure, and provide a reference
      summary of radiation dose estimates associated with MDCT cardiac imaging.

PMID- 15170790
TI  - Potential for correction of fetal obstructive uropathy: time for a randomized,
      controlled trial?

PMID- 15170791
TI  - Trisomy 21 in the mid trimester: sonographic phenotyping of the fetus is the key.

PMID- 15170792
TI  - Three-dimensional (3D) and 4D color Doppler fetal echocardiography using spatio
      temporal image correlation (STIC).
AB  - OBJECTIVE: Color Doppler echocardiography is used to visualize three transverse
      planes: the four-chamber, five-chamber, and three vessels and trachea views.
      Color Doppler spatio-temporal image correlation (STIC) is a new three-dimensional
      (3D) technique allowing the acquisition of a volume of data from the fetal heart
      that is displayed as a cineloop of a single cardiac cycle. The aim of the study
      was to examine the potential of color Doppler STIC to evaluate normal and
      abnormal fetal hearts. METHODS: This prospective study included 35 normal fetuses
      and 27 fetuses with congenital heart defects (CHD) examined between 18 and 35
      weeks of gestation. Volume acquisition was achieved by initiating the image
      capture sequence from the transverse four-chamber view. Volumes were stored for
      later offline evaluation using a personal computer-based workstation in a
      multiplanar mode and as spatial volume rendering. RESULTS: Successful acquisition
      was possible in all 62 cases. The three planes could be demonstrated in 31/35
      healthy fetuses and in 24/27 fetuses with CHD. Spatial volume rendering was
      attempted in 18 fetuses with CHD. In the four normal fetuses with inadequate
      visualization using color Doppler STIC, the region of interest was perpendicular
      to the ultrasound beam. In two fetuses with CHD inadequate visualization was
      related to an enlarged heart in late gestation, in which the entire cardiac
      volume could not be acquired. The third case was an 18-week fetus with complex
      CHD and transposed great vessels in which artifacts were related to confluent
      color signals as a result of low resolution in the reconstructed plane.
      CONCLUSIONS: STIC in combination with color Doppler ultrasound is a promising new
      tool for multiplanar and 3D/4D rendering of the fetal heart. Limitations may be
      found later in gestation in fetuses with large hearts and early in gestation as a
      result of low discrimination of signals. In addition, insonation perpendicular to
      the structure of interest does not image color Doppler signals and should be
      avoided during acquisition.

PMID- 15170794
TI  - Expectant management of tubal ectopic pregnancy: prediction of successful outcome
      using decision tree analysis.
AB  - OBJECTIVE: To establish whether a decision tree based on a combination of
      clinical, morphological and biochemical parameters could be constructed to help
      in the selection of women with tubal ectopic pregnancies for expectant
      management. METHODS: This was a prospective observational study in a tertiary
      referral early pregnancy unit in an inner city teaching hospital. The study group
      consisted of 179 women with ultrasound diagnosis of ectopic pregnancy.
      Demographic, clinical and ultrasound data were recorded in each case at the
      initial visit. In addition all women had a blood sample taken for the
      measurements of serum beta-human chorionic gonadotropin (beta-hCG) and
      progesterone. Clinically stable women with non-viable pregnancies and no signs of
      hematoperitoneum were managed expectantly on an outpatient basis until their
      serum beta-hCG declined to <20 IU/L. Women who developed pelvic pain during
      follow-up and those with non-declining serum beta-hCG were offered surgery.
      RESULTS: A total of 107/179 (59.8%) tubal ectopics were considered suitable for
      expectant management. Ectopic pregnancy resolved spontaneously in 75/107 (70%)
      women, which was 41.9% of the total number of tubal ectopics. Maternal age,
      initial serum beta-hCG and progesterone were all significantly different in
      pregnancies that resolved spontaneously compared to those requiring surgery (P <
      0.05). Initial serum beta-hCG level was the best predictor of the outcome of
      expectant management. These differences enabled a construction of a four-level
      decision tree to estimate the likelihood of successful expectant management.
      CONCLUSIONS: There are significant differences in demographic, ultrasound and
      biochemical findings between spontaneously resolving ectopics and those requiring
      treatment. Decision tree analysis may be used as a guide to estimate the
      probability of successful expectant management in individual cases.

PMID- 15170793
TI  - Application of free-hand three-dimensional echocardiography in the evaluation of
      fetal cardiac ejection fraction: a preliminary study.
AB  - OBJECTIVE: To investigate the feasibility of using free-hand three-dimensional
      (3D) echocardiography to evaluate fetal cardiac function. METHODS: 3D cardiac
      data were collected during screening examinations for 37 normal fetuses with
      gestational ages of between 16 and 26 weeks. Processing of the 3D volumes
      included separation of the end-diastolic and end-systolic slices, segmentation of
      right and left ventricles, measurement of end-diastolic and end-systolic volumes,
      and calculation of the ejection fraction (EF) for each ventricle. In 21 fetuses
      at 21-24 weeks, right and left ventricle volumes and EF were compared. RESULTS:
      Twenty-five cases were appropriate for final statistical analysis. The volume of
      the ventricles increased with gestational age and estimated fetal weight. There
      was no significant trend in the difference between the volumes and EF of the
      right and left ventricles in the 21-24-week subgroup. The mean right and left
      ventricular EF were 54 +/- 11.2% and 57.5 +/- 14.6%, respectively. The mean
      combined EF of ventricles during gestation was 55.1 +/- 10.7% and seemed to
      remain constant during the gestational ages studied. CONCLUSIONS: 3D
      echocardiography can provide estimates of ventricular volume and function and may
      in future be used for evaluation of fetuses with congenital heart disease and
      cardiac dysfunction.

PMID- 15170795
TI  - All five digits of the hands of fetuses with Down syndrome are short.
AB  - OBJECTIVE: To compare mid-gestation sonographic measurements of all five digits
      of the hands of fetuses with Down syndrome with those of normal controls.
      METHODS: Twenty-nine fetuses between 17 and 26 weeks' gestation which had been
      confirmed by karyotyping to have Down syndrome were included in this prospective
      study. Each fetus was scanned once and the digits of only one hand were measured.
      Measurements were compared with those of 302 previously reported normal controls
      matched for gestational age. All measurements were expressed in multiples of the
      gestation-specific normal median (MoM) for each digit. RESULTS: Compared to 1 MoM
      for the length of Digits 1 to 5 from the normal population, the respective values
      in the Down syndrome digits were: 0.94, 0.85, 0.92, 0.88 and 0.85 MoM,
      representing values significantly lower than normal (P < 0.05; t-test).
      CONCLUSIONS: All five digits of the hands of fetuses with Down syndrome are
      shorter than are those of euploid fetuses. Integration of fetal digit measurement
      into the antenatal assessment of selected high-risk cases may be of value
      although confirmation of our findings should be obtained before this measurement
      is incorporated into Down syndrome screening in the general population.

PMID- 15170796
TI  - Prediction of preterm delivery in twin pregnancy: a prospective, observational
      study of cervical length and fetal fibronectin testing.
AB  - OBJECTIVE: To evaluate prospectively cervical length measurements and fetal
      fibronectin detection as predictors of spontaneous preterm delivery in an
      unselected population of twin pregnancies. METHODS: Transvaginal ultrasound
      assessments of cervical length were performed serially at 18, 24, 28 and 32
      weeks' gestation. Receiver-operating characteristic curves were generated at each
      time point to determine the optimal cut-off for cervical length and rate of
      change in cervical length in the prediction of preterm delivery (< 35 weeks). A
      bedside assay for the detection of fetal fibronectin in the maternal vaginal
      secretions was performed prior to cervical length measurements from 24 weeks.
      Likelihood ratios (LRs) were used to assess the performance of each test.
      RESULTS: The spontaneous preterm delivery rate was 16.5% in 91 studied twin
      pregnancies. A cervical length </= 25 mm at 18 weeks (LR+ 9.7, sensitivity 14.3%)
      and </= 22 mm at 24 weeks (LR+ 9.6, sensitivity 28.6%) were the best predictors
      of preterm delivery. A shortening of cervical length >/= 2.5 mm per week between
      18 and 28 weeks' gestation also predicted preterm delivery (LR+ 10.8, sensitivity
      16.7%). There was no relationship between the detection of fetal fibronectin and
      preterm delivery. CONCLUSIONS: This study confirms the value of transvaginal
      ultrasound assessment of cervical length as a predictor of preterm delivery in
      twin pregnancies. However, the poor sensitivity of this test makes it unsuitable
      as a single predictor of preterm delivery. Fetal fibronectin testing does not
      identify twin pregnancies destined to deliver prematurely.

PMID- 15170797
TI  - The role of ultrasound and fetal fibronectin in predicting the length of induced
      labor when the cervix is unfavorable.
AB  - OBJECTIVE: To compare cervical clinical data, ultrasound parameters and fetal
      fibronectin assessment in the prediction of the duration of induced labor when
      the cervix is unfavorable. METHODS: This was a prospective study of 90 pregnant
      women with a Bishop score </= 5 undergoing labor induction. The Bishop score and
      its components, parity, cervical ultrasound parameters and fetal fibronectin
      level were analyzed using Cox's model in order to determine the most predictive
      factors for the duration of the latent and active phases of labor as well as its
      total duration. RESULTS: There was a significant correlation between duration of
      the latent phase and the whole of labor, and digitally assessed cervical
      dilatation (P = 0.003 and P < 0.001, respectively), parity (P = 0.006 and P <
      0.001), the Bishop score (P = 0.019 and P = 0.003) and ultrasound-determined
      cervical length (P = 0.035 and P = 0.003). The length of the active phase of
      labor did not correlate with the cervical status. Funneling did not appear to be
      predictive of the duration of labor and it had a poor correlation with digital
      cervical dilatation. The length of the latent phase and that of the whole of
      labor was significantly longer when cervical dilatation was </= 2 cm (P < 0.001
      in each case), when women were nulliparous (P = 0.002 and P < 0.001) and when
      ultrasound cervical length was >/= 27 mm (P = 0.002 and P = 0.005). CONCLUSION:
      Cervical dilatation as assessed by digital examination is the best predictor of
      the duration of the latent phase and of that of the whole of labor. Ultrasound
      measurement of cervical length is not more accurate at predicting the duration of
      labor than are clinical data.

PMID- 15170798
TI  - Dynamic cervical change during real-time ultrasound: prospective characterization
      and comparison in patients with and without symptoms of preterm labor.
AB  - OBJECTIVES: To compare the incidence of dynamic cervical change (spontaneous real
      time cervical shortening) in singleton patients with and without symptoms of
      preterm labor (PTL). METHODS: A total of 109 patients between 23 and 34 weeks'
      gestation with and without PTL symptoms underwent cervical length ultrasound and
      contraction monitoring over a 10-min period. Cervical length measurements were
      taken at 1-min intervals. Exclusion criteria included ruptured membranes,
      dilation > 3 cm or cerclage. Following the examination, the sonographer made a
      subjective assessment as to whether noticeable dynamic cervical change had
      occurred. A measurement was then made during the application of fundal pressure.
      The initial cervical length, shortest length, maximum change in length and
      incidence of dynamic change were compared between patients with and without PTL
      symptoms. The shortest cervical length was compared to the presence and timing of
      uterine contractions and the measurement during the application of fundal
      pressure. RESULTS: A total of 43 asymptomatic patients and 66 symptomatic
      patients were studied. Compared to asymptomatic patients, patients with PTL
      symptoms had shorter initial lengths, nadir lengths and mean lengths over time as
      well as a greater amount of maximum change. Dynamic cervical change was more
      frequently seen in symptomatic patients (48% vs. 9%, P < 0.001) and was
      associated with uterine contractions (odds ratio 4.6, 95% CI 1.9-10.8). Fundal
      pressure was not able to reproduce the shortest cervical length that occurred
      spontaneously during the observation period. CONCLUSIONS: Dynamic cervical change
      (real-time cervical shortening) is common in patients with PTL symptoms and is
      associated with uterine contractions. Whether this finding enhances the ability
      to predict preterm delivery remains to be elucidated.

PMID- 15170799
TI  - Reduced antioxidant capacity in second-trimester pregnancies with pathological
      uterine perfusion.
AB  - OBJECTIVES: To examine whether pathological perfusion in the second trimester is
      characterized by an altered plasma antioxidant capacity and to investigate
      whether the total antioxidant capacity in maternal plasma is related to the
      clinical outcome of these high-risk pregnancies. METHODS: This was a prospective
      cohort study that included 25 pregnancies with normal and 25 pregnancies with
      pathological uterine perfusion. Doppler ultrasound measurement of uterine
      perfusion was performed between 18 and 23 weeks of gestation. Total antioxidant
      capacity in maternal plasma was measured using a specific photometric assay.
      RESULTS: Plasma antioxidant capacity of pregnant women with pathological uterine
      perfusion (227.3 +/- 4.0 micro mol/L) was significantly lower compared with the
      group with normal uterine perfusion (275.2 +/- 10.5 micro mol/L; P < 0.05). There
      was a significant negative correlation between antioxidant capacity and mean
      pulsatility index of the uterine arteries (r = -0.363; P < 0.05). Patients with
      pathological perfusion and a normal course of pregnancy did not show
      significantly changed values compared with those patients with later pre
      eclampsia or intrauterine growth restriction (235.0 +/- 4.9 micro mol/L vs. 218.6
      +/- 6.7 micro mol/L). CONCLUSIONS: Second-trimester pregnancies with pathological
      uterine perfusion are characterized by a decreased antioxidant capacity in
      maternal plasma. This reduction is related to the impaired uteroplacental blood
      flow, but does not reflect the changes characteristic of the oxidative status for
      diseases like pre-eclampsia since the reduction of the plasma antioxidant
      capacity is not related to the clinical outcome of these high-risk pregnancies.

PMID- 15170801
TI  - Doppler blood flow velocity waveforms in the fetal renal arteries: variability at
      proximal and distal sites in the right and left arteries.
AB  - OBJECTIVE: To investigate variability in pulsatility/resistance indices and
      absolute velocities of blood flow in fetal renal arteries dependent on side and
      sampling site within each vessel. METHODS: Doppler blood flow measurements of
      pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)
      and end-diastolic velocity (EDV) were performed in the renal arteries of 27
      fetuses between 236 and 247 days of gestation. Velocity waveforms were sampled in
      both the right and left renal arteries at two different sites: proximally, close
      to the aorta, and distally, before any major visible bifurcation of the vessels.
      The intraobserver variation was measured in 15 additional fetuses. RESULTS: Mean
      values of PI and RI were similar in the right and left renal arteries and at the
      proximal and distal sampling sites of these arteries. Mean PSV and EDV were
      higher at the proximal compared to the distal site on both sides. For all
      parameters the 95% limits of agreement between measurements made in the right and
      left arteries and at proximal and distal sites were wide but tended to be
      narrower for the left renal artery and at the distal site. Intraclass correlation
      coefficients for intraobserver variability were 0.88, 0.89, 0.83 and 0.81 for PI,
      RI, PSV and EDV, respectively. CONCLUSIONS: It is important to standardize the
      precise site at which Doppler blood flow velocity waveform measurements are made
      in the renal arteries of the fetus. On the basis of our observations, we suggest
      that the left renal artery is the preferred vessel for sampling and that
      measurements should be made in the renal arterial trunk away from the aorta and
      before any visible branches.

PMID- 15170800
TI  - Effect of antenatal glucocorticoid therapy on arterial and venous blood flow
      velocity waveforms in severely growth-restricted fetuses.
AB  - OBJECTIVE: To study the effects of antenatal glucocorticoid (betamethasone)
      therapy on blood flow velocity waveform patterns in the umbilical artery (UA),
      middle cerebral artery (MCA) and ductus venosus (DV) in severely intrauterine
      growth-restricted (IUGR) fetuses. METHODS: Fifty-five severely IUGR fetuses at 24
      34 weeks of gestation were included in the study. The effect of antenatal
      glucocorticoid administration on Doppler findings in the UA, MCA and DV was
      studied using two statistical approaches, namely paired sample analysis and
      multilevel analysis. RESULTS: There were no effects of betamethasone on the
      pulsatility index (PI) of the vessels studied. The only changes noticed during
      the 14 days of observation were a gradual decrease of PI in the MCA, an increase
      in the UA-PI/MCA-PI ratio and an increase in the DV-PI. These changes with time
      may be explained by a progressive and gradual deterioration of the fetal
      condition. CONCLUSION: Antenatal glucocorticoids (betamethasone) do not affect
      fetal Doppler waveform patterns of the UA, MCA and DV in severely IUGR fetuses.

PMID- 15170802
TI  - Sonographic imaging of cervical scars after Cesarean section.
AB  - OBJECTIVE: To investigate whether uterine contractions at the time of a Cesarean
      section have an impact on future presence and location of a cervical Cesarean
      scar. METHODS: A targeted transvaginal ultrasound examination of the fetus,
      uterus and cervix was done in 2973 consecutive women at 14-16 weeks' gestation.
      The sonographer was blinded to the women's previous obstetric histories. The
      presence and location of a sonographic cervical hypoechogenic line, which
      probably represented a Cesarean scar, was recorded. RESULTS: There were 180 women
      with a previous Cesarean section performed before the start of uterine
      contractions and 173 with a Cesarean section performed during contractions in
      labor. The cervical hypoechogenic line was more common in sections performed
      during contractions (75.7% vs. 52.7%; P < 0.001) and was more distally located
      from the internal os (17.9 +/- 9.4 vs. 14.6 +/- 9.1 mm; P = 0.01). A
      hypoechogenic line was observed in 21/2620 women without a previous Cesarean
      section, representing a false-positive rate of 0.8%. CONCLUSION: Cesarean
      sections, especially those done during uterine contractions, are actually
      performed through cervical tissue. This finding is in agreement with the
      physiological process of cervical effacement during contractions.

PMID- 15170803
TI  - Intra- and interobserver repeatability of femur length measurement in early
      pregnancy.
AB  - OBJECTIVE: To assess the intra- and interobserver reproducibility of songographic
      measurement of fetal femur length between 10 and 16 weeks of gestation. METHODS:
      Femur length was measured three times by the same trained observer in each fetus
      of 136 pregnant women. A second trained observer then repeated the measurements.
      The coefficient of variation, intraclass correlation coefficient and
      repeatability coefficient with 95% CIs were calculated for each observer and
      between the two observers. RESULTS: The inter- and intraobserver repeatabilities
      of femur length were good. For interobserver correlation, the coefficient of
      variation was 4.6% (95% CI, 3.0-6.2), the intraclass correlation coefficient was
      0.82 (95% CI, 0.69-0.95) and the repeatability coefficient was 2.1 (95% CI, 1.8
      2.7). For intraobserver correlation, the coefficient of variation was 4.2% (95%
      CI, 3.2-5.6), the intraclass correlation coefficient was 0.91 (95% CI, 0.75-0.97)
      and the repeatability coefficient was 3.23 (95% CI, 2.33-3.86) for Observer 2.
      Similar results were obtained for the other observer. CONCLUSION: Transvaginal
      femur length measurement is technically feasible and easy to perform between 10
      and 16 weeks of gestation. The high degree of intra- and interobserver
      repeatability indicates it to be a reproducible method.

PMID- 15170804
TI  - Is immune-mediated complete fetal atrioventricular block reversible by
      transplacental dexamethasone therapy?
AB  - We report for the first time a fetal case with sustained regression from isolated
      complete to first-degree heart block on transplacental treatment with high-dose
      dexamethasone. Doppler echocardiography is an excellent diagnostic tool in the
      non-invasive assessment of fetal atrioventricular conduction and its anomalies.

PMID- 15170805
TI  - Ultrasound prenatal diagnosis of a lateral facial cleft (Tessier number 7).
AB  - Lateral facial clefting may occur as an isolated phenomenon or in association
      with other disorders. It may originate from a failed penetration of
      ectomesenchyme between the developing maxillary and mandibular prominences, but
      disruptive factors may also occur in a proportion of cases. The frequency of this
      abnormality is estimated as 1 in 50 000-175 000 live births. We describe a case
      of isolated symmetrical lateral facial cleft (number 7 according to the Tessier
      classification) diagnosed prenatally on ultrasound examination at 26 weeks of
      gestation.

PMID- 15170806
TI  - Prenatal sonographic appearance of congenital bile duct dilatation associated
      with renal-hepatic-pancreatic dysplasia.
AB  - We report the prenatal sonographic features of congenital bile duct dilatation
      associated with renal-hepatic-pancreatic dysplasia. The condition was seen at 22
      weeks of gestation and led to termination of pregnancy. This is the first
      description of congenital bile duct dilatation using prenatal sonography. It is
      also the first report of a case in which the features of dysplasia were evident
      in all three of the organs which may be affected, the kidneys, liver and
      pancreas.

PMID- 15170808
TI  - Ultrasound imaging of the pelvic floor. Part II: three-dimensional or volume
      imaging.
AB  - In this second part of a review of pelvic floor ultrasound imaging, current three
      dimensional (3D) ultrasound technology and its use for imaging pelvic floor
      structure and function is described. Recent technical developments enable rapid
      automated volume acquisition in real time, and currently available transducers
      designed for abdominal use are well suited for translabial/transperineal imaging.
      To date, such systems have been used to image the urethra, the levator ani and
      paravaginal supports, prolapse and implants used in pelvic floor reconstruction
      and anti-incontinence surgery. While 3D pelvic floor imaging is a field that is
      still in its infancy, it is already clear that the method has opened up entirely
      new opportunities for the observation of functional anatomy.

PMID- 15170807
TI  - First-trimester diagnosis of sacrococcygeal teratoma: the role of three
      dimensional ultrasound.
AB  - A fetus was suspected of having a sacrococcygeal teratoma (SCT) on routine nuchal
      translucency evaluation by sonography at 12+3 weeks. The patient was referred for
      three-dimensional (3D) sonography to further delineate the extent of the mass. In
      this case, real-time scanning of the mass in 3D mode assisted the diagnosis of
      the mass and patient counseling. We present what we believe to be the first case
      of SCT imaged in the first trimester using 3D ultrasound.

PMID- 15170809
TI  - An unusual case of heterotopic twin pregnancy managed successfully with selective
      feticide.

PMID- 15170810
TI  - Placental surface cyst with contents less echogenic than amniotic fluid on a
      second-trimester ultrasonographic evaluation.

PMID- 15170811
TI  - Edematous polydactyly in Smith-Lemli-Opitz syndrome Type II.

PMID- 15170813
TI  - Differential c-myc expression profiles in normal human bronchial epithelial cells
      following treatment with benzo[a]pyrene, benzo[a]pyrene-4,5 epoxide, and
      benzo[a]pyrene-7,8-9,10 diol epoxide.
AB  - Bronchial epithelial cells are often exposed to airborne mutagens that have the
      potential to induce genetic changes involved in the development of lung cancer.
      Although lung tumors often display alterations in the expression of oncogenes
      and/or tumor suppressor genes, the role of specific chemicals and/or metabolites
      in causing these alterations is not well defined. The polycyclic aromatic
      hydrocarbon (PAH) benzo[a]pyrene (B[a]P), a by-product of combustion, is a
      prevalent airborne environmental mutagen and a constituent of cigarette smoke.
      The primary objective of this study was to compare the effect of B[a]P and two of
      its reactive metabolites, benzo[a]pyrene diol epoxide (BPDE or bay region
      epoxide) and benzo[a]pyrene-4,5-dihydroepoxide (BPE or K-region epoxide), on
      expression of the proto-oncogene c-myc in normal human bronchial epithelial
      (NHBE) cells using a quantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) method. Changes in c-myc gene expression were compared with DNA adduct
      formation, growth inhibition, and cell-cycle progression as determined by (32)P
      postlabelling, neutral red (NR), and flow cytometric analyses, respectively. None
      of the three test compounds altered the levels of 18S ribosomal RNA or beta-actin
      at the concentrations evaluated for c-myc expression, indicating that nonspecific
      changes in gene expression induced by cytotoxicity, for example, were not present
      at the concentrations evaluated. Cells exposed to B[a]P exhibited a dose
      dependent increase in c-myc expression; conversely, a dose-dependent decrease in
      c-myc expression was observed following BPDE exposure. A marginal but
      concentration-dependent increase in c-myc mRNA levels was observed following
      exposure to the K-region epoxide. Our results demonstrated that, although B[a]P
      and its metabolites alter c-myc expression, the parent compound and its
      metabolites produce unequal and contrasting effects on the expression of this
      gene.

PMID- 15170812
TI  - Identification of novel differentially expressed genes by the effect of a high
      fat n-6 diet in experimental breast cancer.
AB  - In previous studies, we demonstrated that high corn oil diets promote the
      development of 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary tumors.
      In this study, we have investigated whether modulation of gene expression is one
      of the mechanisms by which this high-fat diet exerts such effects. Female Sprague
      Dawley rats were induced with DMBA and fed normolipidic (3% corn oil) or high-fat
      (20% corn oil) diet. Screening of genes differentially expressed in
      adenocarcinomas from the high corn oil diet group compared to the control diet
      group was performed with cDNA microarrays. The resulting six upregulated and nine
      downregulated genes were validated by Northern blot and/or reverse transcription
      (RT)-polymerase chain reaction (PCR). Further investigation in a higher number of
      adenocarcinomas showed that in the high-fat n-6 diet group, where the tumor
      phenotype was verified to be more aggressive, the expression of submaxillary
      gland alpha-2u globulin, vitamin D(3)-upregulated protein 1 (VDUP1), H19, and the
      unknown function gene that codifies the expressed sequence tag (EST)-Rn.32385 was
      significantly decreased in comparison with the control group (C). These results,
      together with the fact that VDUP1, H19, and this globulin have been associated
      with cell proliferation and differentiation, open a new line of research about
      how the underexpression of these genes contributes to the stimulating effect of a
      high corn oil diet on experimental mammary carcinogenesis.

PMID- 15170814
TI  - Functional characterization of hepatoma-specific stem cell antigen-2.
AB  - Identification of tumor-specific antigens and genetic pathways may lead to
      potential diagnostic and therapeutic applications in cancer treatment. cDNA
      microarray has been used in cancer gene profiling, but the broad spectrum of data
      accruing and narrow signal-to-noise range of this technology have limited its use
      in rapid identification of highly differentially expressed tumor genes. Here, we
      used a modified suppression subtractive hybridization (SSH) method to isolate a
      small number of highly differentially expressed genes from murine hepatoma cells.
      For functional analysis of these hepatoma-specific genes, we employed the small
      interference RNA (siRNA)-mediated gene silencing method with lentiviral vectors,
      which have the advantages of high delivery efficiency and long lasting effect.
      Stem cell antigen-2 (Sca-2) was identified as one of the highest differentially
      expressed tumor antigens. Lentiviral siRNA successfully suppressed >90% of Sca-2
      expression and the suppression lasted longer than 3 mo. Interestingly, inhibition
      of Sca-2 induced rapid hepatoma cell apoptosis, and the survival Sca-2-negative
      hepatoma cells exhibited high sensitivity to extrinsic tumor necrosis factor
      alpha (TNF-alpha) apoptosis signal but not intrinsic apoptosis signal. Analysis
      of TNF receptor 1 (TNFR1) by flow cytometry and Western blotting indicated that
      Sca-2 expression downregulated cell surface but not de novo synthesis of TNFR1 in
      the hepatoma cells. Together, our results suggested that Sca-2 was a signal
      transducer situated at the nexus of surface molecules regulating death receptor
      mediated apoptosis. The technology illustrated that this method can deduce a
      small number of highly differentially expressed tumor genes that may have
      diagnostic and therapeutic potential.

PMID- 15170815
TI  - Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP
      1 and NF-kappaB in mouse epidermal cl41 cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as
      benzo[a]pyrene (B[a]P), (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide
      (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete
      carcinogens. However, the tumor promotion effects of PAHs remain unclear. We
      therefore investigated the possible activation of activator protein-1 (AP-1) and
      nuclear factor-kappaB (NFkappaB) in mouse epidermal Cl41 cells after different
      PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE),
      and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1
      and NF-kappaB, whereas B[a]P showed only marginal effect on AP-1 activation, and
      B[a]P and CDE had no effect on NF-kappaB activation. Treatment with either
      B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs)
      activation as well as inhibitory subunit kappa-B (IkappaBalpha) phosphorylation
      and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059,
      a specific inhibitor for extracellular signal-regulated protein kinases (ERKs)
      upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a
      dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE
      induced AP-1 activation was also inhibited by overexpressing a dominant negative
      mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases
      (JNKs), and p38 kinase signal transduction pathways are required for AP-1
      induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds
      of PAHs to initiate signaling pathways. Considering the important roles of AP-1
      and NF-kappaB in tumor promotion, we speculated the activation of AP-1 and NF
      kappaB by B[a]PDE and 5-MCDE may involve in their or their parent compounds'
      tumor promotion effects. This study may help in better understanding the tumor
      promotion effects of PAHs.

PMID- 15170816
TI  - Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts.
AB  - Head and neck cancers are characterized by a vigorous desmoplastic response, but
      the contribution of stromal-derived growth factors to the tumor microenvironment
      is poorly understood. We evaluated the expression of stromal growth factor
      expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor
      associated stromal cells. Stromal tissue was isolated from epithelial cells with
      laser capture microdissection (LCMD) and analyzed by cDNA array for the
      expression of TGFalpha, TGF-beta1, HGF, PDGF-alpha, IGFII, bFGF, aFGF, VEGFC, and
      VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent
      histologically normal mucosa, and skin in vitro. Fibroblast populations were
      assessed for TGF-beta1 expression by ELISA and luciferase reporter assay to
      assess protein expression. We identified TGF-beta1 and IGFII overexpression in
      normal and tumor-associated stromal cells; however, only TGF-beta1 was
      significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of
      carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and
      normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated
      persistently elevated levels of TGF-beta1 in CAFs compared to NMF and NDF
      populations. Elevated levels of TGF-beta1 were identified in the stromal
      compartment of HNSCC tumors compared to normal mucosa by immunohistochemical
      analysis. These results suggest that TGF-beta1 mRNA and protein is specifically
      upregulated in CAFs in vitro and in vivo.

PMID- 15170818
TI  - PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine
      transporter probes in the monkey brain.
AB  - (S,S)-2-(alpha-(2-Fluoromethoxyphenoxy)benzyl)morpholine ((S,S)-FMeNER) was found
      to be a selective high-affinity ligand for the norepinephrine transporter (NET).
      (S,S)-FMeNER) was labeled with fluorine-18 (t1/2 = 109.8 min) by O
      fluoromethylation of desfluoromethoxy-(S,S)-FMeNER with [18F]bromofluoromethane.
      An analog, di-deuterated in the fluoromethoxy group ((S,S)-FMeNER-D2), was
      similarly labeled with di-deutero-[18F]bromofluoromethane. These two new
      radioligands were obtained in radiochemical purities greater than 98% and with
      specific radioactivities ranging from 111-185 GBq/micromol at the end of
      synthesis (75 min). After intravenous injection of (S,S)-[18F]FMeNER into
      cynomolgus monkey, PET examination with the head in the field of view revealed
      skull-bound radioactivity, contaminating images of the brain, and indicated fast
      defluorination of the radioligand. Defluorination was much reduced in similar PET
      experiments with (S,S)-[18F]FMeNER-D2. Ratios of radioactivity in the lower
      brainstem, mesencephalon, thalamus, and temporal cortex to striatum obtained with
      (S,S)-[18F]FMeNER-D2 at 160 min after i.v. injection were 1.5, 1.6, 1.3, and 1.5,
      respectively. In another PET experiment, pretreatment of the monkey with the
      selective NET inhibitor, desipramine, decreased the radioactivity ratios in all
      examined regions to near unity (e.g., to a ratio of 1.03 in mesencephalon).
      Labeled metabolites of (S,S)-[18F]FMeNER-D2 or (S,S)-[18F]FMeNER found in plasma
      were all more polar than the parent radioligand. In vitro autoradiography of
      (S,S)-[18F]FMeNER-D2 on post-mortem human brain cryosections furthermore showed
      specific binding to NET in the locus coeruleus and thalamus. (S,S)-[18F]FMeNER-D2
      is the first useful radiofluorinated ligand for imaging brain NET in monkey in
      vivo and is superior to (S,S)-[11C]MeNER because a specific binding peak
      equilibrium is obtained during the PET experiment at a lower noise level.

PMID- 15170817
TI  - Mutation frequencies in murine keratinocytes as a function of carcinogenic
      status.
AB  - A link between genetic abnormalities and carcinogenesis is well established. It
      follows that a correlation exists between mutation frequency and malignant
      progression. We have determined the spontaneous and DNA damage-induced mutation
      frequencies for a series of cell lines derived from SENCAR mouse keratinocytes at
      various stages of malignant progression. Nontumorigenic mouse keratinocytes
      (3PC), papillomas (MT1/2), squamous-cell carcinomas (CH72), and spindle-cell
      carcinomas (CH72T4) were transfected with damaged or undamaged shuttle vectors
      containing a supF mutation reporter gene. The plasmid mutation frequencies were
      determined by blue/white screening. The spontaneous plasmid mutation frequency of
      the squamous-cell carcinoma line was slightly higher than the mutation
      frequencies of the other cell lines tested. The DNA damage induced by triplex
      directed psoralen crosslinks increased the mutation frequencies sixfold to
      eighteenfold in all cell lines tested, with no significant differences among the
      cell lines. Sequence analyses revealed that the spindle-cell carcinoma line had a
      different spontaneous mutation spectrum from the other cell lines. DNA damage
      induced mutations were predominantly point mutations at the triplex-duplex
      junction in all of the cell lines tested, as expected. These data suggested that
      a strong mutator phenotype was not required for progression to an advanced
      malignant phenotype in our model system.

PMID- 15170819
TI  - Isoflurane induces dopamine transporter trafficking into the cell cytoplasm.
AB  - Previous investigations have shown that the binding of a selective hydrophilic
      positron emission tomography radiotracer for the dopamine transporter (DAT)
      (2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-18F-fluoroethyl)nortropane)
      decreased in monkey striatum during deep isoflurane anesthesia.
      Immunohistochemistry experiments suggested but did not prove that isoflurane
      induced a decrease in cell surface DAT. The present investigation was undertaken
      to demonstrate quantitatively the isoflurane-induced internalization of DAT using
      a rapid and relatively uncomplicated biochemical technique in human embryonic
      kidney (HEK-293) cells stably expressing the human DAT (h-DAT) protein.
      Biotinylation followed by Western blot analysis was used to determine the extent
      of change in cell surface expression of the DAT under control conditions and in
      the presence of a clinically relevant concentration of isoflurane. Isoflurane
      treatment for 30 min resulted in a highly significant decrease in the amount of h
      DAT on the cell surface (21 +/- 15% of control; P < 0.01) (mean +/- SD; n = 4).
      These data are consistent with the hypothesis that isoflurane results in
      internalization of DAT from the cell membrane and further validate our
      qualitative results reported previously. In addition, the current results confirm
      the hypothesis that biotinylation can be used to quantitate the extent of
      disappearance of DAT from the cell surface making dose-response studies and
      comparisons of DAT internalization with other general anesthetics practical.

PMID- 15170820
TI  - Prenatal cocaine exposure decreases nigrostriatal dopamine release in vitro:
      effects of age and sex.
AB  - The present study examined the effects of prenatal cocaine (PCOC) exposure, age,
      sex, and estrous phase on the functional development of nigrostriatal dopamine
      (DA) neurons. Striatal tissue was obtained from prepubescent and adult rats of
      both sexes after bidaily exposure to saline (1 ml/kg) or cocaine (20 mg/kg/ml
      saline) from embryonic days 15-21. Tissue levels, basal release, and electrically
      evoked (1 or 8 Hz) overflow of endogenous DA and its metabolite, 3,4
      dihydroxyphenylacetic acid (DOPAC), as well as their efflux in response to
      superfusion with the DA transport blocker, nomifensine (10 microM), were measured
      from superfused striatal slices. Generally, these measures were highest in tissue
      from males and adults. Tissue DA and DOPAC levels and the rate of DA turnover
      were unaffected by PCOC exposure. Slices from PCOC-exposed juvenile and adult
      male rats exhibited significantly reduced basal and electrically evoked DA
      release at both stimulation intensities, in conjunction with higher levels of
      presynaptic DA reuptake. Female rats were largely spared from the effects of PCOC
      exposure, and measures did not vary with estrous phase. These findings
      demonstrate that the effects of PCOC exposure on various parameters of
      nigrostriatal DA neuronal function are not uniform across age, sex, or phases of
      the estrous cycle. These novel alterations in nigrostriatal DA transmission are
      in need of independent replication, but they may have profound implications for
      behavioral activities regulated by these neurons and, thus, may provide a basis
      for sex-selective effects of PCOC in exposed humans. Possible mechanisms of
      deleterious effects of PCOC exposure in select groups are discussed.

PMID- 15170821
TI  - Sigma-1 receptors potentiate epidermal growth factor signaling towards
      neuritogenesis in PC12 cells: potential relation to lipid raft reconstitution.
AB  - We previously demonstrated that overexpression of sigma-1 receptors (sigma-1R)
      potentiated neurite sprouting caused by nerve growth factor in PC12 cells
      (Takebayashi et al. 2002 J Pharmacol Exp Ther 202:1227-1237). In this study we
      examined if sigma-1R may be involved in the action of epidermal growth factor
      (EGF). EGF is conventionally recognized as a mitogenic factor that stimulates
      only the proliferation of various types of cells, including PC12 cells. We found
      here that in sigma-1 receptor-overexpressing PC12 cells (sigma-1R OE cells), EGF
      markedly stimulates neuritogenesis without affecting cellular proliferation. EGF
      receptors (EGFR) are largely reduced in lipid rafts and are enriched in non-raft
      regions in sigma-1R OE cells. The enrichment of EGFR in the non-raft region is
      correlated with enhanced downstream signaling of EGFR including the
      phosphorylation of both EGFR and extracellular signal-regulated kinases (ERKs).
      Destruction of cholesterol-containing rafts by treating cells with methyl-beta
      cyclodextrin also causes a reduction of EGFR in lipid rafts, a concomitant
      increase in the phosphorylation of both EGFR and ERK, and an increase in the EGF
      induced neurite sprouting in wildtype cells. Furthermore, while overexpression of
      sigma-1R increases the level of lipid raft-associated cholesterol, the
      overexpression alters the levels of gangliosides in lipid rafts: GM1 and GM2 are
      decreased, whereas GD1a is increased. We conclude that sigma-1R cause the
      remodeling of lipid rafts, at least by increasing the level of lipid raft
      associated cholesterol and by altering the levels of certain critical lipid raft
      forming gangliosides. sigma-1R may thus play an important role in directing EGF
      signaling towards neuritogenesis, perhaps by shifting EGFR from the lipid raft
      into non-raft regions.

PMID- 15170822
TI  - Regional distribution of SK3 mRNA-containing neurons in the adult and adolescent
      rat ventral midbrain and their relationship to dopamine-containing cells.
AB  - SK3 small conductance, calcium-activated potassium channels play an important
      role in regulating the activity of mesencephalic dopamine (DA) neurons. In the
      present series of experiments, in situ hybridization techniques were used to
      compare SK3 and tyrosine hydroxylase (TH) mRNA expression throughout the
      rostrocaudal extent of the ventral midbrain in juvenile and adult rats. SK3 mRNA
      was found exclusively in areas that also contained large numbers of DA neurons
      including the substantia nigra (SN), the ventral tegmental area, and related cell
      groups (VTA-A10). An anteroposterior and mediolateral gradient in SK3 mRNA
      hybridization was apparent in the VTA-A10 but not in the SN. Younger rats
      appeared to possess higher levels and less regional variation in TH and SK3
      transcripts. These results are consistent with previous studies reporting
      differential expression of SK3 protein within the midbrain and suggest that
      variations in SK3 channel distribution could contribute to differences in
      dopamine-related functions in the rat.

PMID- 15170823
TI  - Induction of long-term depression is associated with decreased dendritic length
      and spine density in layers III and V of sensorimotor neocortex.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are currently the
      most widely investigated models of the synaptic mechanisms underlying learning
      and memory. Previous research has shown that induction of LTP increases measures
      of pyramidal cell dendritic morphology in the hippocampus and layers III and V of
      the neocortex. However, to date there are no reports on the direct effects of LTD
      induction on dendritic morphology. Here, we investigated the effects of LTD
      induction on sensorimotor pyramidal cell dendritic morphology. Rats carried a
      stimulating electrode in the corpus callosum (midline) and a recording electrode
      in the right sensorimotor cortex. Each rat received low-frequency stimulation
      composed of 900 pulses at 1 Hz or handling daily for a total 15 days. Evoked
      potentials (EPs) of the transcallosal pathway were recorded in the right
      hemisphere before and after the 15 days of stimulation or handling. The rats were
      then perfused with saline and the brains were immediately processed for Golgi-Cox
      staining. Our results show that LTD induction is related to decreases in
      dendritic length and spine density both in layers III and V as well as a decrease
      in dendritic branch complexity in layer V of the sensorimotor cortex. Thus,
      neuronal alterations following modifications in neocortical synaptic efficacy may
      provide a general mechanism for the physical instantiation of learning and
      memory.

PMID- 15170824
TI  - Differential properties of GABAergic synaptic connections in rat hippocampal cell
      cultures.
AB  - Based on the effect of prolonged tetanic stimulation (30 Hz, 4 sec), we divided
      GABAergic synaptic connections in hippocampal cell cultures into two groups:
      connections facilitated ( approximately 45%) and connections depressed (
      approximately 55%) by the tetanic stimulation. In order to reveal possible
      reasons for the differential effect of the tetanization, we compared several
      properties of the connections belonging to both groups. We found that, on
      average, evoked IPSCs in the connections facilitated by the tetanization have a
      smaller amplitude and larger coefficient of variation (CV) of IPSC amplitude
      compared to connections depressed by the tetanization. We also estimated quantal
      parameters for both groups of connections assuming that transmitter release is
      reasonably described by a binomial distribution. We found that a background
      release probability (P) is substantially lower in the connections facilitated by
      the tetanization (P approximately 0.5) than in the connections depressed by the
      tetanization (P approximately 0.9) and suggest that this difference may underlie
      the differential effect of the tetanization. We also found that the tetanization
      induces the opposite effect on connections made by distinct presynaptic neurons
      with the same postsynaptic cell (convergent connections) in a fraction of
      postsynaptic neurons studied (3 out of 9). These results support the idea that
      properties of the presynaptic neuron are of primary importance for the observed
      differential effect of the tetanization, but they do not exclude a role of the
      postsynaptic neuron in this effect.

PMID- 15170825
TI  - Dopamine D4 receptor-deficient mice, congenic on the C57BL/6J background, are
      hypersensitive to amphetamine.
AB  - Mice lacking the dopamine D4 receptor subtype (D4R-/-) are supersensitive to
      methamphetamine and cocaine. We sought to expand and refine earlier experiments
      performed on F2 generation D4R-/- mice by lengthening the behavioral session,
      utilizing an N10 D4R-/- incipient congenic C57BL/6J line (D4R-/- mice backcrossed
      with wildtype C57BL/6J mice for 10 successive generations), and investigating
      whether dopamine D4Rs are necessary for the expression of behavioral
      sensitization to amphetamine. The D4R-/- mice demonstrated an enhanced and dose
      dependent increase in amphetamine-stimulated activity compared to wildtype mice
      following acute administrations of amphetamine. For the behavioral sensitization
      experiments, separate groups of mice received either repeated administrations of
      the same dose of amphetamine or a subthreshold dose of amphetamine (2 mg/kg) 28
      days following pretreatment with either saline, 1.0, 3.0, or 10.0 mg/kg
      amphetamine. The D4R-/- mice displayed an enhanced dose-dependent sensitized
      response to repeated amphetamine administrations compared to their wildtype
      littermates in both behavioral sensitization paradigms. Our present results
      further support the importance of dopamine D4Rs in psychostimulant-mediated
      locomotion and neural plasticity.

PMID- 15170826
TI  - Navigator gating and volume tracking for double-triggered cardiac proton
      spectroscopy at 3 Tesla.
AB  - Respiratory motion compensation based on navigator echoes for double-triggered
      cardiac proton spectroscopy at 3.0 T is presented. The navigators measure the
      displacement of the liver-lung interface during free breathing. This information
      allows for double triggering on a defined window within the respiratory cycle and
      on a defined trigger delay after the R-wave based on the ECG. Furthermore, it
      allows the excitation volume to be shifted by the determined respiratory
      displacement within the defined window in real-time (volume tracking). Static and
      motion phantom experiments were performed in this study, and it was demonstrated
      that volume tracking permits the suppression of signal from tissue next to the
      localized volume. However, triggering on a defined respiratory position is still
      necessary to achieve high spectral quality, because shimming and water
      suppression calibration are only optimal for a small window of the respiratory
      cycle. Single-volume spectra obtained in the myocardial septum of healthy
      subjects are presented.

PMID- 15170827
TI  - Method for reduced SAR T1rho-weighted MRI.
AB  - A reduced specific absorption rate (SAR) version of the T(1rho)-weighted MR pulse
      sequence was designed and implemented. The reduced SAR method employs a partial k
      space acquisition approach in which a full power spin-lock pulse is applied to
      only the central phase-encode lines of k-space, while the remainder of k-space
      receives a low-power spin-lock pulse. Acquisition of high- and low-power phase
      encode lines are interspersed chronologically to minimize average power
      deposition. In this way, the majority of signal energy in the central portion of
      k-space receives full T(1rho)-weighting, while the average SAR of the overall
      acquisition can be reduced, thereby lowering the minimum safely allowable TR. The
      pulse sequence was used to create T(1rho) maps of a phantom, an in vivo mouse
      brain, and the brain of a human volunteer. In the images of the human brain, SAR
      was reduced by 40% while the measurements of T(1rho) differed by only 2%. The
      reduced SAR sequence enables T(1rho)-weighted MRI in a clinical setting, even at
      high field strengths.

PMID- 15170828
TI  - Observation of significant signal voids in images of large biological samples at
      11.1 T.
AB  - Proton MRI of large biological samples were obtained on an 11.1 T / 40 cm
      instrument. Images were obtained of a fixed human brain and a large piece of
      fresh beef. The proton MR images demonstrate severe distortions within these
      conductive samples, indicative of shortened electrical wavelengths and wave
      behavior within the sample. These observations have significant implications with
      respect to the continuing evolution of MR to higher magnetic field strengths on
      large samples, particularly on humans.

PMID- 15170831
TI  - Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord.
AB  - Proton MR spectroscopy ((1)H-MRS) provides indices of neuronal damage in the
      central nervous system (CNS); however, it has not been extensively applied in the
      spinal cord. This work describes an optimized proton spectroscopy protocol for
      examination of the human cervical spinal cord. B(0) field mapping of the cord
      revealed periodic inhomogeneities due to susceptibility differences with
      surrounding tissue. By combining field maps and experimental data, we found that
      the optimum voxel size was 9 x 7 x 35 mm(3) placed with the inferior end of the
      voxel above vertebral body C2. Metabolite concentrations were determined in the
      cervical cord in six healthy controls by short-echo point-resolved spectroscopy
      (PRESS) volume localization. The results were compared with metabolite
      concentrations in the brainstem, cerebellum, and cortex in the same individuals.
      The concentrations in the cervical cord were as follows: N-acetyl-aspartate (NAA)
      17.3 +/- 0.5, creatine (Cr) 9.5 +/- 0.9, and choline 2.7 +/- 0.5 mmol/l. The NAA
      concentration was significantly lower in the cord than in the brainstem (Mann
      Whitney, P < 0.025), and higher than in the cortex (P < 0.005) and cerebellum (P
      < 0.005). Cr was significantly lower in the cord than in the cerebellum (P <
      0.05). There were no significant differences between Cr concentrations in the
      spinal cord compared to the cortex and brainstem.

PMID- 15170829
TI  - In vivo 1H MRS of brain injury and repair during acute SIV infection in the
      macaque model of neuroAIDS.
AB  - The metabolic response of the rhesus macaque brain during acute simian
      immunodeficiency virus (SIV) infection was investigated with in vivo (1)H MR
      spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once
      or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11
      13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had
      subsequent reduction of this ratio (ANOVA, P < 10(-6)). There were significant
      increases in Cho/Cr (20%, P = 0.04) and MI/Cr (14%, P = 0.003) at 11 dpi. At 13
      dpi a 7.7% decrease (P = 0.02) in NAA/Cr was observed, while Cho/Cr was no longer
      significantly different from baseline. At 27 dpi Cho/Cr was decreased to 18% (P =
      0.004) below preinoculation values, while NAA/Cr and MI/Cr were at baseline
      values. Absolute concentrations of Cho, MI, and NAA showed a similar time course,
      with no observed changes in Cr. There was a strong correlation between Cho/Cr
      change and plasma viral load (r(s) = 0.79, P < 0.01). Acute SIV produces
      extensive metabolic abnormalities in the brain, which may reflect inflammation
      and neuronal injury, which are reversed with immunological control of the virus.
      Similar events are likely to occur in acutely HIV-infected people, and may
      explain the neurobehavioral symptoms associated with acute HIV infection.

PMID- 15170830
TI  - Single-shot two-echo technique for simultaneous measurement of GABA and creatine
      in the human brain in vivo.
AB  - A single-shot, two-echo method for the simultaneous detection of multiple-quantum
      (MQ)-filtered gamma-aminobutyric acid (GABA) and creatine (Cr) was developed and
      demonstrated in the human brain in vivo at 3 Tesla. The simultaneously measured
      Cr singlet served as a navigator for the spectral phase of GABA and any frequency
      shift during measurements due to drift in the static magnetic field (B(0)) or
      subject movement, as well as an internal concentration reference. In addition,
      the use of a double-band frequency-selective MQ filter for C(3) and C(4)
      methylene protons of GABA provided a very robust measurement of GABA, with
      excellent suppression of overlapping metabolites such as Cr and glutathione (GSH)
      in each single scan. Contamination from overlapping macromolecules was also
      demonstrated to be negligible with this method. The GABA-to-Cr ratio was 0.09 +/-
      0.03 (mean +/- SD, N = 17) and the estimated concentration of GABA in the
      frontoparietal region of the human brain in vivo was 0.66 +/- 0.19 micromol/g
      (mean +/- SD, N = 17) with the internal reference method, and 0.69 +/- 0.18
      micromol/g (mean +/- SD, N = 17) with the external reference method. The observed
      pattern of GABA doublet was consistent among all subjects, with a frequency
      separation of approximately 13 Hz.

PMID- 15170832
TI  - Radiofrequency power deposition utilizing thermal imaging.
AB  - Wavelength effects influence radiofrequency (RF) power deposition distributions
      and limit magnetic resonance (MR) medical applications at very high magnetic
      fields. The power depositions in spherical saline gel phantoms were deduced from
      proton resonance shift thermal maps at both 1.5 T and 3.0 T over a range of
      conductivities. Phase differences before and after RF heating were measured for
      both a quadrature head coil and a circular surface coil. A long echo time (TE)
      pulse sequence with a 3D phase unwrap algorithm provided increased thermal
      sensitivity. The measured thermal maps agreed with a model of eddy-current
      heating by circularly polarized oscillating RF fields in a conducting dielectric
      sphere. At 3.0 T, thermal maps were acquired with a <0.32 degrees C temperature
      rise at 4 W. Proton resonance shift thermal maps provided a measure of hot spots
      in very-high-field MR imaging (MRI), in which both the phase sensitivity and
      signal-to-noise ratio (SNR) were increased. The method provides a means of
      studying the heat distribution generated by RF coils excited by clinical pulse
      sequences.

PMID- 15170833
TI  - Acute cerebral ischemia in rats studied by Carr-Purcell spin-echo magnetic
      resonance imaging: assessment of blood oxygenation level-dependent and tissue
      effects on the transverse relaxation.
AB  - Acute cerebral ischemia has been shown to be associated with an enhanced
      transverse relaxation rate in rat brain parenchyma, chiefly due to the blood
      oxygenation level-dependent (BOLD) effect. In this study, Carr-Purcell R(2) (CP
      R(2)), acquired both with short and long time intervals between centers of
      adiabatic pi-pulses (tau(CP)), was used to assess the contributions of BOLD and
      tissue effects to the transverse relaxation in two brain ischemia models of rat
      at 4.7 T. R(1rho) and diffusion MR images were also acquired in the same animals.
      During the first minutes of global ischemia, the long tau(CP) R(2) in brain
      parenchyma increased, whereas the short tau(CP) R(2) was unchanged. Based on the
      simulations, and using constraints of intravascular BOLD effect on parenchymal
      R(2), the former observation was ascribed to be due to susceptibility changes
      arising in the extravascular compartment. R(1rho) declined almost immediately
      after the onset of focal cerebral ischemia, and further declined during the
      evolution of ischemic damage. Interestingly, short tau(CP) CP R(2) started to
      decline after some 20 min of focal ischemia and declined over a time course
      similar to that of R(1rho), indicating that it may be an MRI marker for
      irreversible tissue changes in cerebral ischemia. The present results show that
      CP R(2) MRI can reveal both tissue- and blood-derived contrast changes in acute
      cerebral ischemia.

PMID- 15170834
TI  - T2 of articular cartilage in the presence of Gd-DTPA2-.
AB  - T(2) information and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are
      both used to characterize articular cartilage. They are currently obtained in
      separate studies because Gd-DTPA(2-) (which is needed for dGEMRIC) affects the
      inherent T(2) information. In this study, T(2) was simulated and then measured at
      8.45 T in 20 sections from two human osteochondral samples equilibrated with and
      without Gd-DTPA(2-). Both the simulations and data demonstrated that Gd-DTPA(2-)
      provides a non-negligible mechanism for relaxation, especially with higher (1 mM)
      equilibrating Gd-DTPA(2-) concentrations, and in areas of tissue with high T(2)
      (due to weak inherent T(2) mechanisms) and high tissue Gd-DTPA(2-) (due to a low
      glycosaminoglycan concentration). Nonetheless, T(2)-weighted images of cartilage
      equilibrated in 1 mM Gd-DTPA(2-) showed similar T(2) contrast with and without Gd
      DTPA(2-), demonstrating that the impact on T(2) was not great enough to affect
      identification of T(2) lesions. However, T(2) maps of the same samples showed
      loss of conspicuity of T(2) abnormalities. We back-calculated inherent T(2)'s
      (T(2,bc)) using a T(2)-relaxivity value from a 20% protein phantom (r(2) = 9.27
      +/- 0.09 mM(-1)s(-1)) and the Gd-DTPA(2-) concentration calculated from T(1,Gd).
      The back-calculation restored the inherent T(2) conspicuity, and a correlation
      between T(2) and T(2,bc) of r = 0.934 (P < 0.0001) was found for 80 regions of
      interest (ROIs) in the sections. Back-calculation of T(2) is therefore a viable
      technique for obtaining T(2) maps at high equilibrating Gd-DTPA(2-)
      concentrations. With T(2)-weighted images and/or low equilibrating Gd-DTPA(2-)
      concentrations, it may be feasible to obtain both T(2) and dGEMRIC information in
      the presence of Gd-DTPA(2-) without such corrections. These conditions can be
      designed into ex vivo studies of cartilage. They appear to be applicable for
      clinical T(2) studies, since pilot clinical data at 1.5 T from three volunteers
      demonstrated that calculated T(2) maps are comparable before and after "double
      dose" Gd-DTPA(2-) (as utilized in clinical dGEMRIC studies). Therefore, it may be
      possible to perform a comprehensive clinical examination of dGEMRIC, T(2), and
      cartilage volume in one scanning session without T(2) data correction.

PMID- 15170835
TI  - In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI:
      illustration of targeted delivery.
AB  - The purpose of this study was to determine if MnSO(4)/doxorubicin (DOX) loaded
      liposomes could be used for in vivo monitoring of liposome concentration
      distribution and drug release using MRI. In vitro results show that T(1)
      shortening correlates with MnSO(4) concentration. Using a temperature-sensitive
      liposome formulation, it was found that MnSO(4) release significantly shortened
      T(1). This feature, therefore, suggests that content release can also be measured
      with these MnSO(4)-loaded liposomes. The feasibility of monitoring this drug
      delivery and release-imaging agent was shown in a murine tumor model. Upon tumor
      heating, nonthermally sensitive liposomes selectively but heterogeneously
      accumulated in the tumor region. The thermally sensitive liposomes showed a clear
      pattern of accumulation at the periphery of the tumor, concordant with the
      release temperature of this formulation (39-40 degrees C). This liposome contrast
      agent has potential for use with hyperthermia by providing individualized
      monitoring of tissue drug concentration distribution during or after treatment.
      This would allow for: 1) modification of treatment variables to improve the
      uniformity of drug delivery, and 2) provide a means to select patients most
      likely to benefit from this liposomal drug treatment. Additionally, the drug
      loading method used for this liposome is applicable to a wide range of drugs,
      thereby broadening its applicability. The method is also applicable to other
      liposomal formulations with triggered release mechanisms.

PMID- 15170836
TI  - MR-trackable intramyocardial injection catheter.
AB  - There is growing interest in delivering cellular agents to infarcted myocardium
      to prevent postinfarction left ventricular remodeling. MRI can be effectively
      used to differentiate infarcted from healthy myocardium. MR-guided delivery of
      cellular agents/therapeutics is appealing because the therapeutics can be
      precisely targeted to the desired location within the infarct. In this study, a
      steerable intramyocardial injection catheter that can be actively tracked under
      MRI was developed and tested. The components of the catheter were arranged to
      form a loopless RF antenna receiver coil that enabled active tracking.
      Feasibility studies were performed in canine and porcine myocardial infarction
      models. Myocardial delayed-enhancement (MDE) imaging identified the infarcted
      myocardium, and real-time MRI was used to guide left ventricular catheterization
      from a carotid artery approach. The distal 35 cm of the catheter was seen under
      MRI with a bright signal at the distal tip of the catheter. The catheter was
      steered into position, the distal tip was apposed against the infarct, the needle
      was advanced, and a bolus of MR contrast agent and tissue marker dye was injected
      intramyocardially, as confirmed by imaging and postmortem histology. A pilot
      study involving intramyocardial delivery of magnetically labeled stem cells
      demonstrated the utility of the active injection catheter system.

PMID- 15170837
TI  - Neuroprotective effects of an immunosuppressant agent on diffusion/perfusion
      mismatch in transient focal ischemia.
AB  - The immunosuppressant FK506 (tacrolimus) exerts potent neuroprotection following
      focal ischemia in animals; however, the separate effects of FK506 on the ischemic
      core and penumbra have not been reported. The ischemic penumbra is clinically
      defined as the difference between a large abnormal area on perfusion-weighted
      imaging (PWI) and a smaller lesion on diffusion-weighted imaging (DWI). The goal
      of this study was to determine the effect of FK506 on DWI/PWI match and mismatch
      areas in transient focal ischemia in rats. Twelve rats were subjected to 1 hr of
      transient middle cerebral artery (MCA) occlusion, and given an intravenous
      injection of a placebo (N = 6) or 1 mg/kg FK506 (N = 6) immediately before
      reperfusion. Magnetic resonance imaging (MRI) was performed during MCA occlusion,
      and 0.5, 1, and 24 hr after reperfusion. FK506 significantly protected the
      ischemic brain only in the mismatch cortex where the initial apparent diffusion
      coefficient (ADC) was normal and there was a mild reduction of cerebral blood
      flow (CBF). This is the first report to describe the protective effects of FK506
      on ischemic penumbra, as measured by DWI/PWI mismatch. The findings provide
      direct evidence for the utility of DWI/PWI mismatch as a guideline for
      therapeutic intervention with FK506.

PMID- 15170839
TI  - Efficiency of flow-driven adiabatic spin inversion under realistic experimental
      conditions: a computer simulation.
AB  - Continuous arterial spin labeling (CASL) using adiabatic inversion is a widely
      used approach for perfusion imaging. For the quantification of perfusion, a
      reliable determination of the labeling efficiency is required. A numerical method
      for predicting the labeling efficiency in CASL experiments under various
      experimental conditions, including spin relaxation, is demonstrated. The approach
      is especially useful in the case of labeling at the carotid artery with a surface
      coil, as consideration of the experimental or theoretical profile of the B(1)
      field is straightforward. Other effects that are also accounted for include
      deviations from a constant labeling gradient, and variations in the blood flow
      velocity due to the cardiac cycle. Assuming relevant experimental and
      physiological conditions, maximum inversion efficiencies of about 85% can be
      obtained.

PMID- 15170838
TI  - Optimized interleaved whole-brain 3D double inversion recovery (DIR) sequence for
      imaging the neocortex.
AB  - For a substantial number of individuals with neurological disorders, a
      conventional MRI scan does not reveal any obvious etiology; however, it is
      believed that abnormalities in the neocortical gray matter (GM) underlie many of
      these disorders. Attempts to image the neocortex are hindered by its thin,
      convoluted structure, and the partial volume (PV) effect. Therefore, we developed
      a 3D version of the double inversion recovery (DIR) sequence that incorporates an
      optimized interleaved (OIL) strategy to improve efficiency and allow high
      quality, high-resolution imaging of GM.

PMID- 15170840
TI  - Dynamic field map estimation using a spiral-in/spiral-out acquisition.
AB  - The long readout times of single-shot acquisitions and the high field strengths
      desired for functional MRI (fMRI) using blood oxygenation level-dependent (BOLD)
      contrast make functional scans sensitive to magnetic field inhomogeneity. If it
      is not corrected during image reconstruction, field inhomogeneity can cause
      geometric distortions in the images when Cartesian k-space trajectories are used
      or blurring with spiral acquisitions. Many traditional methods to correct for
      field inhomogeneity distortions rely on a static field map measured with the use
      of images that are themselves distorted. In this work, we employ a regularized
      least-squares approach to jointly estimate both the undistorted image and field
      map at each acquisition using a spiral-in/spiral-out pulse sequence. Simulation
      and phantom studies show that this method is accurate and stable over a time
      series. Human functional studies show that the jointly estimated field map may be
      more accurate than standard field map estimates in the presence of respiration
      induced phase oscillations, leading to better detection of functional activation.
      The proposed method measures a dynamic field map that accurately tracks magnetic
      field drift and respiration-induced phase oscillations during the course of a
      functional study.

PMID- 15170841
TI  - Fast frequency mapping with balanced SSFP: theory and application to proton
      resonance frequency shift thermometry.
AB  - A method is presented for the rapid acquisition of frequency maps based on
      multiecho balanced steady-state free precession (balanced SSFP, fast imaging with
      steady precession (True FISP), fast imaging employing steady-state excitation
      (FIESTA), or balanced fast field echo (FFE)). This technique was applied to
      measure temperature changes within a gel phantom based on the temperature
      sensitive water proton-resonance frequency. The frequency was determined as the
      slope of a linear fit of the phases measured at different TEs along the echo
      train. The signal-to-noise ratio (SNR) of multiecho SSFP was analyzed for
      different parameters, such as relaxation times and flip angle, as well as for
      different local field inhomogeneities. The theoretical and experimental results
      were compared with results from the established multiecho fast low-angle shot
      (FLASH) method. Depending on the given tissue parameters, a significant increase
      in the accuracy of the frequency/temperature shift estimation compared to FLASH
      was observed. Furthermore, balanced SSFP can be used with very short TRs without
      generating a saturation-related signal loss, which is essential for real-time
      temperature mapping.

PMID- 15170842
TI  - Method for spatially interleaving two images to halve EPI readout times: two
      reduced acquisitions interleaved (TRAIL).
AB  - A new MRI method is presented that can generate images using half the normal
      readout time or, more usefully, half the number of phase-encode steps, combining
      two readouts per excitation. However, the corresponding data are interleaved in
      image space-not in k-space, as in many other fast techniques. This gives a
      resilience to the phase-related artifacts that can occur in many other techniques
      due to subject motion. A modified stimulated-echo experiment is used to create
      two low-resolution images from a single sequence. The magnetization that
      contributes to these images is nonuniformly distributed within each pixel,
      forming two sinusoidal waves in quadrature, with an oscillation period of exactly
      two pixels. Since only half of each pixel contributes significant signal, the two
      images can be interleaved to create a full image with twice as many pixels and
      double the resolution. When the technique is used in the phase-encode direction,
      the effective imaging time is halved, though with two readouts per TR period.
      When two half-length echo-planar readouts are used, the method can also reduce
      blurring and distortion by halving the effective readout time for echo-planar
      imaging (EPI). For even further improvements, the technique can be combined with
      partial Fourier or parallel imaging.

PMID- 15170843
TI  - Referenceless PRF shift thermometry.
AB  - The proton resonance frequency (PRF) shift provides a means of measuring
      temperature changes during minimally invasive thermotherapy. However,
      conventional PRF thermometry relies on the subtraction of baseline images, which
      makes it sensitive to tissue motion and frequency drift during the course of
      treatment. In this study, a new method is presented that eliminates these
      problems by estimating the background phase from each acquired image phase. In
      this referenceless method, a polynomial is fit to the background phase outside
      the heated region in a weighted least-squares fit. Extrapolation of the
      polynomial to the heated region serves as the background phase estimate, which is
      then subtracted from the actual phase. The referenceless method is demonstrated
      on a phantom during laser heating, 0 degrees temperature rise images of in vivo
      human liver, interstitial laser ablation of porcine liver, and transurethral
      ultrasound ablation of canine prostate. A good correlation between temperature
      maps reconstructed with the referenceless and subtraction methods was found.

PMID- 15170844
TI  - Microsphere-induced embolic stroke: an MRI study.
AB  - Despite the many studies of the middle cerebral artery occlusion (MCAO) model,
      efficient therapy for stroke is still lacking, emphasizing the need for further
      development and characterization of experimental stroke models. In the present
      study, the rather unexplored multifocal microsphere-induced stroke model in rats
      was characterized by multiparametric MRI. We induced microembolic infarction in a
      group of Sprague-Dawley rats by injecting a dose of about 1000 50-microm
      polyethylene microspheres intracranially from the external carotid artery.
      Diffusion-, perfusion-, and T(2)-weighted MRI were used to evaluate the infarct
      development during and following the first 3 hr after microsphere injection (N =
      20). The animals were also imaged at 12-hr (N = 8), 24-hr (N = 17), and 48-hr (N
      = 5) time points. After the final imaging time point, the brains were removed and
      sectioned into 2-mm-thick slices, and infarct volumes were measured by 2,3,4
      triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion
      coefficient (ADC) maps, a volume of reduced ADC appeared 0.5-1.0 hr
      postinjection, and by the 3-hr time point the volume of ADC reduction had
      increased to a size of 5% +/- 1% (mean +/- SEM) of the brain hemisphere. The
      lesion volume increased significantly (P < 0.01) to 16% +/- 2% of the hemisphere
      volume at the 12-hr time point, while at 24 hr the lesion (15% +/- 2% of the
      hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion
      deficit resulting from the microsphere injection was immediate, going from a
      cerebral blood flow index (CBF(i)) of 74% +/- 3% at the time of microsphere
      injection to 68% +/- 2% of the contralateral mean at 3 hr (P < 0.05), to 55% +/-
      4% of the contralateral values at 12 hr (P < 0.05), and to 57% +/- 2% of the
      contralateral mean at 24 hr (P < 0.001). The lesion development in the
      microsphere-induced stroke model was found to be slower than in the MCAO model,
      and continued up to the 24-48-hr time point.

PMID- 15170845
TI  - TRIM: TR independent multislice imaging.
AB  - This article introduces a novel concept to overcome the dependence of image
      contrast on spatial positioning parameters such as the number of slices and slice
      separation in multislice measurements: TR-independent multislice (TRIM)
      acquisition allows the number of slices in a single measurement to remain
      independent of the repetition time TR. Ramped TRIM (rTRIM) allows the distance
      between the sections excited in each repetition to remain independent of the
      distance between the reconstructed slices. Even images from overlapping slices
      can be acquired without crosstalk between the images of adjacent slices due to
      spatially overlapping excitation profiles. This concept is based on a special
      reordering scheme: Within a single TR acquisition, steps are only taken from a
      fraction of all slices. This necessitates attribution of different phase-encoding
      steps to different slices within each repetition cycle. The reordering scheme can
      be derived by the use of a design matrix. The imaging properties of the technique
      are discussed theoretically and illustrated by a point spread function analysis
      based on simulations and phantom measurements. Potential sources of artifacts are
      identified and methods for their prevention are developed. Optimized
      implementations with different T(1)-weighted sequences such as spin echo (SE),
      turbo spin echo (TSE), and spoiled gradient echo acquisitions are shown on normal
      volunteers with imaging parameters used in routine diagnosis.

PMID- 15170846
TI  - Removal of EPI Nyquist ghost artifacts with two-dimensional phase correction.
AB  - Odd-even echo inconsistencies result in Nyquist ghost artifacts in the
      reconstructed EPI images. The ghost artifacts reduce the image signal-to-noise
      ratio and make it difficult to correctly interpret the EPI data. In this article
      a new 2D phase mapping protocol and a postprocessing algorithm are presented for
      an effective Nyquist ghost artifacts removal. After an appropriate k-space data
      regrouping, a 2D map accurately encoding low- and high-order phase errors is
      derived from two phase-encoded reference scans, which were originally proposed by
      Hu and Le (Magn Reson Med 36:166-171;1996) for their 1D nonlinear correction
      method. The measured phase map can be used in the postprocessing algorithm
      developed to remove ghost artifacts in subsequent EPI experiments. Experimental
      results from phantom, animal, and human studies suggest that the new technique is
      more effective than previously reported methods and has a better tolerance to
      signal intensity differences between reference and actual EPI scans. The proposed
      method may potentially be applied to repeated EPI measurements without subject
      movements, such as functional MRI and diffusion coefficient mapping.

PMID- 15170847
TI  - High-resolution fast spin echo imaging of the human brain at 4.7 T:
      implementation and sequence characteristics.
AB  - In this work, a number of important issues associated with fast spin echo (FSE)
      imaging of the human brain at 4.7 T are addressed. It is shown that FSE enables
      the acquisition of images with high resolution and good tissue contrast
      throughout the brain at high field strength. By employing an echo spacing (ES) of
      22 ms, one can use large flip angle refocusing pulses (162 degrees ) and a low
      acquisition bandwidth (50 kHz) to maximize the signal-to-noise ratio (SNR). A new
      method of phase encode (PE) ordering (called "feathering") designed to reduce
      image artifacts is described, and the contributions of RF (B(1)) inhomogeneity,
      different echo coherence pathways, and magnetization transfer (MT) to FSE signal
      intensity and contrast are investigated. B(1) inhomogeneity is measured and its
      effect is shown to be relatively minor for high-field FSE, due to the self
      compensating characteristics of the sequence. Thirty-four slice data sets (slice
      thickness = 2 mm; in-plane resolution = 0.469 mm; acquisition time = 11 min 20 s)
      from normal volunteers are presented, which allow visualization of brain anatomy
      in fine detail. This study demonstrates that high-field FSE produces images of
      the human brain with high spatial resolution, SNR, and tissue contrast, within
      currently prescribed power deposition guidelines.

PMID- 15170849
TI  - Carbon blacks as EPR sensors for localized measurements of tissue oxygenation.
AB  - New electron paramagnetic resonance (EPR) oximetry probes were identified in the
      class of carbon black materials. These compounds exhibit very high oxygen
      sensitivity and favorable EPR characteristics for biological applications. At low
      pO(2), the linewidth is particularly sensitive to changes in oxygen tension
      (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was
      demonstrated in vivo: the pO(2) was measured in muscle in which the blood flow
      was temporarily restricted as well as in tumor-bearing mice during a carbogen
      breathing challenge. The responsiveness to pO(2) was stable in muscle for at
      least 3 months. No toxicity was observed using these materials in cellular
      experiments and in histological studies performed 2, 7, and 28 days after
      implantation. In view of their EPR characteristics (high sensitivity) as well as
      the well-characterized production procedure that make them available on a large
      scale, these probes can be considered as very promising tools for future
      developments in EPR oximetry.

PMID- 15170848
TI  - In vitro release of vascular endothelial growth factor from gadolinium-doped
      biodegradable microspheres.
AB  - A drug delivery vehicle was constructed that could be visualized noninvasively
      with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was
      used to fabricate microspheres containing vascular endothelial growth factor
      (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid
      (Gd-DTPA). The microspheres were characterized in terms of size, drug and
      contrast agent encapsulation, and degradation rate. The PLGA microspheres had a
      mean diameter of 48 +/- 18 microm. The gadolinium loading was 17 +/- 3 microg/mg
      polymer and the VEGF loading was 163 +/- 22 ng/mg polymer. Electron microscopy
      revealed that the Gd was dispersed throughout the microspheres and it was
      confirmed that the Gd loading was sufficient to visualize the microspheres under
      MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period
      of approximately 6 weeks in three phases: a burst, followed by a slow steady
      state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be
      effectively used to deliver drugs in a sustained manner, while being monitored
      noninvasively with MRI.

PMID- 15170851
TI  - Quantitation of erythrocyte pentose pathway flux with [2-13C]glucose and 1H NMR
      analysis of the lactate methyl signal.
AB  - A simple and sensitive NMR method for quantifying excess (13)C-enrichment in
      positions 2 and 3 of lactate by (1)H NMR spectroscopy of the lactate methyl
      signal is described. The measurement requires neither signal calibrations nor the
      addition of a standard and accounts for natural abundance (13)C-contributions. As
      a demonstration, the measurement was applied to approximately 3 micromol of
      lactate generated by erythrocyte preparations incubated with [2-(13)C]glucose to
      determine the fraction of glucose metabolized by the pentose phosphate pathway
      (PP). PP fluxes were estimated from the ratio of excess (13)C-enrichment in
      lactate carbon 3 relative to carbon 2 in accordance with established metabolic
      models. Under baseline conditions, PP flux accounted for 7 +/- 2% of glucose
      consumption while in the presence of methylene blue, a classical activator of PP
      activity, its contribution increased to 27 +/- 10% of total glucose consumption
      (P < 0.01).

PMID- 15170850
TI  - Lactate isotopomer analysis by 1H NMR spectroscopy: consideration of long-range
      nuclear spin-spin interactions.
AB  - Lactate is a key metabolite and its rates of cellular uptake and release, its
      production rates from glucose and glycogen, and its interconversion rate with
      pyruvate are important determinants of cellular energy production. If lactate
      precursors such as pyruvate and glucose are labeled appropriately with (13)C,
      (1)H NMR spectroscopy provides a means of quantifying lactate production from
      each source and allows measurement of all these rates within a single experiment.
      However, due to the multiplicities of the resonance lines (from nuclear spin-spin
      couplings) in lactate (13)C isotopomers, the (1)H NMR spectra were found to be
      more complex than expected, requiring determination of all spin-spin interactions
      in this anion. All such values were determined for lactate and its precursor
      pyruvate. The method was then applied to simultaneously measure the rates of
      exogenous lactate uptake and rates of release of glucose-, glycogen-, and
      pyruvate-derived lactate in the isolated perfused rat heart.

PMID- 15170852
TI  - Prolonged T*2 values in newborn versus adult brain: Implications for fMRI studies
      of newborns.
AB  - The neonatal brain possesses higher water content, lower macromolecular
      concentration, and reduced synaptic density than is found in the brain of a 1
      year-old child. Changes in MRI characteristics of brain such as relaxation times
      accompany rapid changes in brain during early postnatal development. It was
      hypothesized that T(*)(2) values found in newborns would be significantly higher
      than those found in 9-month-old children and adults as measured at 1.5 T. Spoiled
      gradient echo measurements of T(*)(2) within the brains of newborns, 9-month
      olds, and adults confirmed this hypothesis. The results have implications with
      regard to functional MRI studies in newborns since, in general, BOLD signal
      optimization is achieved when echo times TE are set equal to the T(*)(2) values
      of the tissue of interest. Since significantly longer T(*)(2) values are found in
      newborns, it is suggested that the TE values employed for fMRI studies of
      newborns should be increased to maximize BOLD signal intensity changes and
      improve the overall reliability of fMRI results in newborns.

PMID- 15170853
TI  - Magnetic resonance electrical impedance tomography at 3 Tesla field strength.
AB  - Magnetic resonance electrical impedance tomography (MREIT) is a recently
      developed imaging technique that combines MRI and electrical impedance tomography
      (EIT). In MREIT, cross-sectional electrical conductivity images are reconstructed
      from the internal magnetic field density data produced inside an electrically
      conducting object when an electrical current is injected into the object. In this
      work we present the results of electrical conductivity imaging experiments, and
      performance evaluations of MREIT in terms of noise characteristics and spatial
      resolution. The MREIT experiment was performed with a 3.0 Tesla MRI system on a
      phantom with an inhomogeneous conductivity distribution. We reconstructed the
      conductivity images in a 128 x 128 matrix format by applying the harmonic B(z)
      algorithm to the z-component of the internal magnetic field density data. Since
      the harmonic B(z) algorithm uses only a single component of the internal magnetic
      field data, it was not necessary to rotate the object in the MRI scan. The root
      mean squared (RMS) errors of the reconstructed images were between 11% and 35%
      when the injection current was 24 mA.

PMID- 15170854
TI  - Improved magnetization preparation for navigator steady-state free precession 3D
      coronary MR angiography.
AB  - The purpose of this work was to investigate a new magnetization preparation
      scheme for navigator steady-state free precession (SSFP) 3D coronary MR
      angiography (MRA) that executes the navigator and fat saturation pulses in steady
      state after the dummy RFs in order to minimize the delay between the
      magnetization preparation and the image echoes. Compared to the previous
      preparation scheme that executes the navigator and fat saturation pulses before
      the dummy RFs, the new scheme was found to provide more effective motion
      suppression, significantly improved blood-to-myocardium contrast-to-noise ratio
      (46%, P < 0.001) at slightly but insignificantly decreased blood signal-to-noise
      ratio (SNR) (2%, P = 0.73), significantly reduced fat SNR (32%, P < 0.001), and
      better overall image quality (P = 0.05; Wilcoxon paired sample signed rank test).

PMID- 15170856
TI  - Growth and specification: fly Pax6 homologs eyegone and eyeless have distinct
      functions.
AB  - Development requires not only the correct specification of organs and cell types
      in the right places (pattern), but also the control of their size and shape
      (growth). Many signaling pathways control both pattern and growth and how these
      two are distinguished has been something of a mystery. In the fly eye, a Pax6
      homolog (eyeless) controls eye specification together with several other genes.
      Now Dominguez et al.1 show that Notch signaling controls eye growth through a
      second Pax6 protein (Eyegone). In mice and humans the single Pax6 gene appears to
      encode both specification and growth controlling proteins through alternative
      mRNA splicing.

PMID- 15170855
TI  - A new bone to pick: osteoblasts and the haematopoietic stem-cell niche.
AB  - Two recent publications highlight the role of bone-forming cells, the
      osteoblasts, in controlling the development of neighboring haematopoietic stem
      cells (HSCs).1,2 Using two distinct transgenic mouse models, one using the
      conditional deletion of the Bone Morphogenetic Protein Receptor 1A (BMPR1A) gene,
      the other using over-expression of an active PTH/PTHrP receptor (PPR) mutant
      within osteoblasts, the authors show parallel, concordant increases in the
      generation of trabecular osteoblasts and the number of HSCs. In situ staining
      showed that rarely cycling HSCs sporadically attach to endosteal osteoblasts,
      while in vitro assays indicated that ligation of Jag1 on osteoblasts by Notch1 on
      HSCs promotes HSC proliferation. These two independent works have revived and
      revitalized the notion that osteoblasts are a major, defining component of the
      HSC niche within the bone marrow (BM). This minireview discusses these results in
      the context of other recent studies of mesenchymal cells within the BM
      microenvironment, presents one potential unified model of the functional anatomy
      of the BM HSC niche, and highlights new questions raised by these and other
      studies of osteoblasts and HSCs.

PMID- 15170857
TI  - ALIX-ing phospholipids with endosome biogenesis.
AB  - Endosomes, which comprise a diverse population of membrane vesicles and tubules,
      sort proteins and lipids to various cellular destinations. The organization and
      functions of these pleiomorphic cellular organelles have been extensively
      studied. Matsuo et al.1 now provide new exciting evidence on the role of
      lysobiphosphatidic acid (LBPA), a resident phospholipid of internal vesicles of
      the late endosome, in the control of membrane invagination and endosome
      biogenesis. In vivo, LBPA functions are controlled by the adaptor protein Alix
      and depend on pH gradients along the endosomal compartments.

PMID- 15170858
TI  - Nitric oxide and the enigma of cardiac hypertrophy.
AB  - In pathological conditions associated with persistent increases in hemodynamic
      workload (old myocardial infarction, high blood pressure, valvular heart
      disease), a number of signalling pathways are activated in the heart, all of
      which promote hypertrophic growth of the heart, characterised at the cellular
      level by increases in individual cardiac myocyte size. Some of these pathways are
      required for a successful adaptation to cardiac injury. Other pathways are
      maladaptive, however, as they lead to progressive contractile dysfunction and
      heart failure. The free radical gas nitric oxide and natriuretic peptides, both
      of which are produced in the heart, have emerged as endogenous inhibitors of
      maladaptive hypertrophy signalling. Overall, it appears that cardiac hypertrophy
      is controlled by an interplay of pro- and antihypertrophic signalling networks.
      This delicate balance can tip towards adaptation or heart failure. In the future,
      patients living with cardiac disease may benefit from therapeutic strategies
      targeting maladaptive hypertrophy signalling pathways.

PMID- 15170859
TI  - Murine Hermansky-Pudlak syndrome genes: regulators of lysosome-related
      organelles.
AB  - In the mouse, at least 16 genes regulate vesicle trafficking to specialized
      lysosome-related organelles, including platelet dense granules and melanosomes.
      Fourteen of these genes have been identified by positional cloning. All 16 mouse
      mutants are models for the genetically heterogeneous human disease, Hermansky
      Pudlak Syndrome (HPS). Five HPS genes encode known vesicle trafficking proteins.
      Nine genes are novel, are found only in higher eukaryotes and encode members of
      three protein complexes termed BLOCs (Biogenesis of Lysosome-related Organelles
      Complexes). Mutations in murine HPS genes, which encode protein co-members of
      BLOCs, produce essentially identical phenotypes. In addition to their well-known
      effects on pigmentation, platelet function and lysosome secretion, HPS genes
      control a wide range of physiological processes including immune recognition,
      neuronal functions and lung surfactant trafficking. Studies of the molecular
      functions of HPS proteins will reveal important details of vesicle trafficking
      and may lead to therapies for HPS.

PMID- 15170860
TI  - hnRNP K: one protein multiple processes.
AB  - Since its original identification as a component of the heterogeneous nuclear
      ribonucleoprotein (hnRNP) complex, K protein has been found not only in the
      nucleus but also in the cytoplasm and mitochondria and is implicated in chromatin
      remodeling, transcription, splicing and translation processes. K protein contains
      multiple modules that, on one hand, bind kinases while, on the other hand,
      recruit chromatin, transcription, splicing and translation factors. Moreover, the
      K- protein-mediated interactions are regulated by signaling cascades. These
      observations are consistent with K protein acting as a docking platform to
      integrate signaling cascades by facilitating cross-talk between kinases and
      factors that mediate nucleic-acid-directed processes. Comparison of K across
      species reveals that it is an essential factor in metazoans, but not in yeast.
      Although some of the K protein interactions and functions are conserved in
      eukaryotes from yeast to man, the mammalian protein seems to play a wider role.
      The greater diversity of mammalian K protein interactions and function may
      reflect gain of novel docking sites and expansion evolutionary of gene expression
      networks.

PMID- 15170861
TI  - The ends of a continuum: genetic and temperature-dependent sex determination in
      reptiles.
AB  - Two prevailing paradigms explain the diversity of sex-determining modes in
      reptiles. Many researchers, particularly those who study reptiles, consider
      genetic and environmental sex-determining mechanisms to be fundamentally
      different, and that one can be demonstrated experimentally to the exclusion of
      the other. Other researchers, principally those who take a broader taxonomic
      perspective, argue that no clear boundaries exist between them. Indeed, we argue
      that genetic and environmental sex determination in reptiles should be seen as a
      continuum of states represented by species whose sex is determined primarily by
      genotype, species where genetic and environmental mechanisms coexist and interact
      in lesser or greater measure to bring about sex phenotypes, and species where sex
      is determined primarily by environment. To do otherwise limits the scope of
      investigations into the transition between the two and reduces opportunities to
      use studies of reptiles to advance understanding of vertebrate sex determination
      generally.

PMID- 15170862
TI  - Synthesis of immune modulators by smooth muscles.
AB  - The primary function of smooth muscle cells is to contract and alter the
      stiffness or diameter of hollow organs such as blood vessels, the airways and the
      gastrointestinal and urogenital tracts. In addition to purely structural
      functions, smooth muscle cells may play important metabolic roles, particularly
      in various inflammatory responses. In cell culture, these cells have been shown
      to be metabolically dynamic, synthesizing and secreting extracellular matrix
      proteins, glycosaminoglycans and a wide variety of cell-cell signaling proteins,
      such as interleukins, chemokines and peptide growth factors. Secreted cell
      signaling proteins participate in the inflammatory response of smooth muscle
      containing organs, and some can also stimulate smooth muscle migration,
      proliferation and contraction. The cellular signaling pathways controlling
      synthesis of these signaling proteins are similar to those used by cells
      mediating innate immunity and may contribute to pathogenesis of diverse diseases
      including atherosclerosis, asthma, inflammatory bowel diseases and preterm labor.
      Appreciating the role of smooth muscle cells in these diseases may lead to better
      understanding of the beneficial effects of anti-inflammatory drugs as well as
      identification of new targets for anti-inflammatory therapy.

PMID- 15170863
TI  - Apoptosis initiated by dependence receptors: a new paradigm for cell death?
AB  - A distinct group of receptors including DCC, UNC5, RET and Ptc1 is known to
      function in ligand-dependent neuronal growth and differentiation or axon
      guidance. Acting as "dependence receptors", they may also regulate neuronal cell
      survival by inducing apoptosis in the absence of cognate ligand. Receptor
      initiated apoptosis requires proteolytic (caspase) cleavage and exposure of a pro
      apoptotic region in the cytoplasmic domains of the receptors. In contrast,
      classical apoptosis induced by growth factor or cytokine deprivation involves
      loss of survival signaling without receptor cleavage. DCC, UNC5, RET and Ptc1 are
      downregulated or mutated in diverse cancers, and show properties characteristic
      of tumor suppressors, consistent with their ability to promote neuronal cell
      death. Dysfunctional dependence receptors have been linked to the loss of
      specific neurons in certain inherited and neurodegenerative diseases. Dependence
      receptor-initiated apoptosis represents a novel paradigm for the controlled
      removal of specific cells during neural development and elimination of malignant
      cells that have strayed beyond regions of ligand availability.

PMID- 15170864
TI  - Continuous tooth replacement: the possible involvement of epithelial stem cells.
AB  - Epithelial stem cells have been identified in integumental structures such as
      hairs and continuously growing teeth of various rodents, and in the gut. Here we
      propose the involvement of epithelial stem cells in the continuous tooth
      replacement that characterizes non-mammalian vertebrates, as exemplified by the
      zebrafish. Arguments are based on morphological observations of tooth renewal in
      the zebrafish and on the similarities between molecular control of hair and tooth
      formation. Dissection of the molecular cascades underlying the regulation of the
      epithelial stem cell niche might open perspectives for new regenerative treatment
      strategies in clinical dentistry.

PMID- 15170865
TI  - The androgen receptor mRNA.
AB  - Androgens (testosterone), acting via the androgen receptor (AR) a nuclear
      transcription factor, regulate male sexual development and body composition. In
      addition, AR expression plays an important role in the proliferation of human
      prostate cancer and confers a better prognosis in breast cancer. AR mRNA
      stability is central to the regulation of AR expression in prostate and breast
      cancer cells, and recent studies have demonstrated binding by members of the
      ELAV/Hu and poly(C) RNA-binding protein families to a highly conserved UC-rich
      element in the 3'-untranslated region of AR mRNA, with functional impact on AR
      protein expression. Remarkably, a CAG trinucleotide repeat in exon 1 of the AR,
      the length of which has been linked to prostate cancer survival, is also a target
      for multiple RNA-binding proteins from a variety of human and murine tissues. In
      this review, we will detail the current knowledge of the mechanisms involved in
      regulating AR mRNA stability, the nature, potential role and structural biology
      of several novel AR mRNA-protein interactions, and the implications for novel
      therapeutics in human prostate cancer.

PMID- 15170866
TI  - Bioengineering nitrogen acquisition in rice: can novel initiatives in rice
      genomics and physiology contribute to global food security?
AB  - Rice is the most important crop species on earth, providing staple food for 70%
      of the world's human population. Over the past four decades, successes in
      classical breeding, fertilization, pest control, irrigation and expansion of
      arable land have massively increased global rice production, enabling crop
      scientists and farmers to stave off anticipated famines. If current projections
      for human population growth are correct, however, present rice yields will be
      insufficient within a few years. Rice yields will have to increase by an
      estimated 60% in the next 30 years, or global food security will be in danger.
      The classical methods of previous green revolutions alone will probably not be
      able to meet this challenge, without being coupled to recombinant DNA technology.
      Here, we focus on the promise of these modern technologies in the area of
      nitrogen acquisition in rice, recognizing that nitrogen deficiency compromises
      the realization of rice yield potential in the field more than any other single
      factor. We summarize rice-specific advances in four key areas of research: (1).
      nitrogen fixation, (2). primary nitrogen acquisition, (3). manipulations of
      internal nitrogen metabolism, and (4). interactions between nitrogen and
      photosynthesis. We develop a model for future plant breeding possibilities,
      pointing out the importance of coming to terms with the complex interactions
      among the physiological components under manipulation, in the context of ensuring
      proper targeting of intellectual and financial resources in this crucial area of
      research.

PMID- 15170867
TI  - Animal models of T-cell-mediated skin diseases.

PMID- 15170868
TI  - A new evolutionary scenario for the Mycobacterium tuberculosis complex.

PMID- 15170870
TI  - CF: an X-ray database to assess effect of aerosolized tobramycin.
AB  - This paper assesses the effectiveness of aerosolized tobramycin (TOBI) on cystic
      fibrosis (CF) lung disease, using a radiologic tool. The published tool, the age
      based severity curve (ABS), is derived from Brasfield scoring of chest X-rays
      (CXR). This study evaluates both the usefulness of the ABS as an assessment tool
      and the effectiveness of TOBI. Thirty-eight patients were treated with TOBI.
      Twenty-four treated with dornase alfa were excluded. Fourteen patients, aged 2
      months to 22 years (mean, 17 months of TOBI treatment), comprised the study
      group. Radiographs were obtained over a mean of 7.8 years (SD = 6.5 years; range,
      9 months-18 years). Two hundred and eighty-two CXR of TOBI patients were analyzed
      following the ABS protocol. Rate of decline in radiologic status of the TOBI
      group and ABS were compared. Also, TOBI was assessed by comparing rate of decline
      before and after initiation of treatment. The TOBI group's radiologic assessment
      was compared to its rate of decline in pulmonary function studies and published
      population data. Rate of decline in ABS was 0.175 Brasfield points/year vs. 0.150
      points/year in the TOBI group (P < 0.001). Before treatment, the TOBI group's
      rate of decline was 0.169 Brasfield points/year; after treatment, it was 0.150
      points/year (P = 0.02). Forced vital capacity revealed a statistically
      significant slowing in rate of decline on TOBI. Although not statistically
      significant, rate of decline in forced expiratory volume at 1 sec showed a
      similar trend. The degree of slowing in decline is similar to that previously
      reported for pulmonary function studies.

PMID- 15170869
TI  - Pulmonary arterial hypertension in children.
AB  - Pulmonary arterial hypertension is a serious progressive condition with a poor
      prognosis if not identified and treated early. Because the symptoms are
      nonspecific and the physical findings can be subtle, the disease is often
      diagnosed in its later stages. Remarkable progress has been made in the field of
      pulmonary arterial hypertension over the past several decades. The pathology is
      now better defined, and significant advances have occurred in understanding the
      pathobiologic mechanisms. Risk factors have been identified, and the genetics
      have been characterized. Advances in technology allow earlier diagnosis as well
      as better assessment of disease severity. Therapeutic modalities such as new
      drugs, e.g., epoprostenol, treprostinil, and bosentan, and
      surgical/interventional options, e.g., transplantation and atrial septostomy,
      which were unavailable several decades ago, have had a significant impact on
      prognosis and outcome. Thus, despite our inability to cure pulmonary arterial
      hypertension, advances in medical treatments over the past two decades have
      resulted in significant improvement in outcomes for children with various forms
      of pulmonary arterial hypertension. This report is a review the current state of
      the art for pulmonary arterial hypertension in 2004, with an emphasis on
      childhood pulmonary arterial hypertension and specific recommendations for
      current practice and future directions.

PMID- 15170871
TI  - Dietary intake, physical activity, body mass index, and childhood asthma in the
      Third National Health And Nutrition Survey (NHANES III).
AB  - Childhood asthma may be affected by dietary changes and increased body mass
      related to a sedentary lifestyle, although the mechanisms are poorly understood.
      To test this hypothesis, we used data from the National Health and Nutrition
      Survey (NHANES III) from 1988-1994, including 7,904 children. We analyzed cross
      sectional information on body mass index (BMI = weight/height2), physical
      activity (hr/day viewing television), dietary intake (24-hr recall), and vitamin
      C intake (60 mg/day). The probability of self-reported asthma or wheezing
      relating to risk factors was calculated by logistic regression. After controlling
      for dietary intake, physical activity, and sociodemographic variables, asthma
      risk was three times higher for children aged 6-16 years in the highest
      percentiles of BMI (>95th percentile) when compared to children in percentiles 25
      49 (OR = 3.44; 95% CI, 1.49-7.96). No increase was observed in children aged 2-5
      years. Low vitamin C intake was marginally related to self-reported current
      wheezing in children aged 6-16 years. Our results show that increased BMI may
      influence asthma prevalence in children, but further investigation is needed.

PMID- 15170872
TI  - Longitudinal study of oxidative status in 312 cystic fibrosis patients in stable
      state and during bronchial exacerbation.
AB  - In cystic fibrosis (CF), there is an imbalance in the oxidant/antioxidant system,
      leading to oxidative damage. The aim of this study was to assess antioxidant
      scavenger deficiencies and lipid peroxide variations in three clinical situations
      (stable status, acute exacerbation, and after intravenous antibiotic treatment).
      The objective was also to correlate oxidative stress with age, nutritional
      status, and respiratory function. The study included prospectively 312
      consecutive patients and 53 controls. Antioxidants (vitamin A, vitamin E,
      carotenoids, and glutathione) and oxidative markers (malondialdehyde and lipid
      peroxides) were measured in plasma. Regression analyses were performed.
      Antioxidant levels were lower in CF patients than in controls. These levels
      decreased during acute exacerbation and increased after antibiotic treatment.
      Carotenoid levels were not modified by infection or age. Only vitamin A and
      carotenoid levels were positively correlated to body mass index. Antioxidant
      levels were correlated to forced expiratory volume at 1 sec. Lipid peroxidation
      markers were lower in patients than in controls. Their levels decreased during
      infection, and increased after antibiotic treatment. Impaired lung function was
      correlated with elevated malondialdehyde levels. In conclusion, this study
      demonstrates antioxidant deficiency in a very large cohort of CF patients.
      Carotenoid and vitamin E deficiencies occur early in the course of the disease.
      Antioxidants decrease with bronchial infection. By contrast, nutritional
      disorders did not modify antioxidant levels during acute exacerbations. Thus,
      pulmonary disorders rather than nutritional disorders seem to be essential in the
      imbalance of the oxidant/antioxidant system. Results concerning glutathione and
      oxidative-marker levels highlighted the fact that their plasma values do not
      reflect oxidative stress in the respiratory tract.

PMID- 15170873
TI  - Inspired gas temperature in ventilated neonates.
AB  - The warming and humidification of inspired gases for ventilated neonates are
      routine. There are no data on the temperature of the gas at the airway opening in
      ventilated neonates. Is the inspired gas temperature at the airway opening, as
      expected and set on the humidifier, around 37 degrees C? We aimed to measure
      temperature at the airway opening and compare this with the circuit temperature.
      This was an observational study in a neonatal intensive care unit. Twenty-five
      mechanically ventilated infants were studied. All had humidifiers with chamber
      temperature set at 36 degrees C and the circuit temperature set at 37 degrees C.
      Two temperature probes were inserted and rested at the circuit-exit and at the
      airway opening, and temperatures were measured for 2 min in each infant. At this
      time, the circuit temperature was also noted. The mean (SD) temperature at the
      airway opening in infants nursed in incubators was 34.9 (1.2) degrees C, compared
      with radiant warmers where the mean (SD) was 33.1 (0.5) degrees C. The mean (SD)
      difference in temperature from the circuit temperature probe to the airway
      opening was greater under radiant warmers, with a mean (SD) drop of 3.9 (0.6)
      degrees C compared with a mean (SD) drop of 2.0 (1.3) degrees C in the
      incubators. In conclusion, the temperature at the circuit temperature probe does
      not reflect the temperature at the airway opening. Inspired gas temperatures are
      lower than the expected 37 degrees C with the normal circuits and usual
      humidifier settings.

PMID- 15170874
TI  - Randomized, double-blinded trial of low-dose dexamethasone: II. Functional
      residual capacity and pulmonary outcome in very low birth weight infants at risk
      for bronchopulmonary dysplasia.
AB  - We previously reported on a 7-day course of dexamethasone starting at 0.5
      mg/kg/day in intubated very low birth weight (VLBW) infants, 7-14 days of age,
      with increased dynamic pulmonary compliance and decreased bronchopulmonary
      dysplasia (BPD). The effect of low-dose dexamethasone on functional residual
      capacity (FRC) in VLBW infants is unknown. The objective of this study was to
      compare the effect of two regimens of moderately early dexamethasone on FRC and
      passive respiratory compliance (Crs) in VLBW infants at risk for BPD. Sixty-two
      intubated VLBW infants were randomized (double-blinded) at 7-21 days of age; 29
      patients (mean birth weight, 839 g) received "high" dose dexamethasone (0.5
      mg/kg/day for 3 days, 0.25 mg/kg/day for 3 days, and 0.1 mg/kg/day on day 7,
      total dose of 2.35 mg/kg), and 33 infants (mean birth weight, 830 g) received
      "low-dose" dexamethasone (0.2 mg/kg/day for 3 days and 0.1 mg/kg/day for 4 days,
      total dose of 1 mg/kg). FRC and Crs were measured with the nitrogen washout
      technique and single breath occlusion technique, before and on days 2, 5, and 7
      of therapy. Clinical outcome and early neurodevelopmental follow-up were
      evaluated. FRC significantly increased in the high-dose (19.3 ml/kg at baseline
      to 34 ml/kg on day 7; P < 0.001) and low-dose (18.1 ml/kg at baseline to 30.3
      ml/kg on day 7; P < 0.001) dexamethasone groups when compared to baseline. There
      was a significant increase in Crs and a decrease in FiO2 within each group. The
      improvements in FRC and Crs were comparable between groups, and specific
      compliances (Crs/FRC) were not different. There were no significant differences
      in other clinical outcome parameters, including BPD and neurodevelopmental
      outcome. In conclusion, there are significant increases in FRC during a 7-day
      course of moderately early dexamethasone in VLBW infants. The lower total dose (1
      mg/kg) appears as effective as the higher total dose of dexamethasone (2.35
      mg/kg) in increasing FRC. Comparable significant increases in Crs were observed
      in both groups of infants. Additional long-term follow-up is underway.

PMID- 15170876
TI  - Effect of DNase on exercise capacity in cystic fibrosis.
AB  - DNase can reduce viscosity and facilitate expectoration of airway secretions in
      cystic fibrosis (CF) lung disease. We evaluated its effect on exercise
      performance in relation to resting pulmonary function. Fifteen sputum-producing
      CF patients (aged 9-28 years; FEV1 22-83% predicted) performed spirometry, body
      plethysmography, nitrogen washout, and incremental cardiopulmonary exercise
      testing before and after 8 weeks of first-time treatment with daily inhaled
      rhDNase. Most subjects reported increased amounts and fluidity of sputum. The
      effect on objective parameters was heterogeneous, without statistical
      significance. Groupwise, FEV1 increased by 6% without correlation to baseline
      values; individual patients gained up to 40%. Indices of hyperinflation and air
      trapping were slightly raised. Maximal workload and oxygen uptake (V'O2)
      increased by up to 20% in a number of patients. The treatment effect on V'O2 was
      neither related to baseline levels of pulmonary function and exercise capacity
      nor to the change in FEV1. Ventilatory equivalents for oxygen and carbon dioxide
      during exercise were slightly but insignificantly lower after DNase treatment;
      minimal O2 saturation was unaffected. We conclude that improvement of exercise
      performance with DNase is restricted to a subgroup of CF patients and may not be
      predicted or identified by spirometry and subject report alone.

PMID- 15170875
TI  - Respiratory illness in children attending daycare.
AB  - Daycare attendance has been associated with an increased occurrence of
      respiratory illness, but little is known about which children are at particular
      risk. Our objectives were to determine the association between the incidence of
      respiratory illness and attendance in daycare, and to determine if the risk is
      modified by selected sociodemographic factors. Using a prospective study design,
      185 newborns in Prince Edward Island, Canada, were recruited between January 1997
      March 2000. They were followed for 2 years or until the end-date of the study in
      September 2000. Information on daycare attendance and respiratory illness was
      collected twice monthly by telephone interviews of the parent. Comparing those
      who were ever in daycare more than 1 day per week (daycare group) to those who
      were not, the association between daycare and illness was stronger among children
      15 months of age compared to those less than 3 months of age (P < 0.001), and
      stronger among those without siblings than those with siblings (P < 0.001). Among
      those not in daycare, family income was inversely related to the proportion of
      days with an illness episode: 9.8% (CI, 6.0, 13.6) if family income was < $30,000
      vs. 5.2% (CI, 4.1, 6.3) if > or = $30,000 (P = 0.003). However, in the daycare
      group, income did not influence illness, with respective values of 14.6% (CI,
      12.4, 16.8) vs. 13.2% (CI, 12.1, 14.3) (P = 0.21). In conclusion, younger
      children and those with siblings may be less susceptible to illness associated
      with daycare, and daycare attendance may negate a protective effect of higher
      income on respiratory illness.

PMID- 15170877
TI  - Symptoms, lung function, and beta2-adrenoceptor polymorphisms in a birth cohort
      followed for 10 years.
AB  - As little is known about the natural history of bronchial responsiveness and the
      development of wheezing symptoms in early childhood, a cohort of children at risk
      of allergy, whose lung function and bronchial responsiveness had been measured in
      the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order
      to determine the role of neonatal measurements on wheezing history and later lung
      function. A potential role for beta-2 adrenoceptor (beta2AR) polymorphisms in
      these relationships was also sought as a secondary objective. Of the original 73
      children, wheezing history was available in 65 (89%), and 49 (67%) attended the
      laboratory for physiological measurements and genotyping of beta2AR. Wheezing was
      categorized as occurring 1) only before the fourth birthday, 2) after the fourth
      birthday, or 3) never. No relation was seen between neonatal and later lung
      function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P
      = 0.03). Increased neonatal bronchial responsiveness was associated with
      transient wheeze <4 years but not with later wheeze. Neonatal V'maxFRC was
      reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of
      beta2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was
      typical of classical asthma, as it was strongly related to atopy and bronchial
      responsiveness at age 10. In conclusion, we confirmed the association of neonatal
      bronchial responsiveness with both early wheezing and later lung function. We
      also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung
      function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to
      early measurements of lung function or bronchial responsiveness.

PMID- 15170878
TI  - Clinical value of obtaining sputum and cough swab samples following inhaled
      hypertonic saline in children with cystic fibrosis.
AB  - Prompt detection and treatment of lower respiratory tract infection are essential
      in the management of patients with cystic fibrosis (CF), who often have signs or
      symptoms of respiratory infection without any pathogens being isolated from
      sputum or cough swab specimens. The aims of this study were to assess the
      efficacy and clinical value of obtaining sputum and oropharyngeal cough swab
      samples following induction with hypertonic saline (HS) in this group of
      patients. Forty-three outpatients with CF, mean age 7.2 years (range, 1.8-12.9
      years), were recruited over a 2-year period. Nebulized salbutamol was
      administered, followed by 6% HS. Sputum was preferentially obtained before and
      after HS induction if possible. If the patient was not able to expectorate,
      oropharyngeal cough swabs were taken instead. Four patients were able to
      expectorate sputum before and 19 after HS induction. The procedure was tolerated
      in 41 of 43 patients. Pathogens were isolated from 13 patients' HS-induced
      samples, but not from their corresponding preinduced specimens, and 4 patients'
      preinduced specimens cultured organisms which were not identified from their HS
      induced samples. Significant changes were made in the management of 13 (30.2%)
      patients directly resulting from the positive culture of pathogens only from HS
      induced samples. Cultures from oropharyngeal cough swab or expectorated sputum
      specimens following inhalation of HS provide additional microbiological
      information which is of clinical value and may lead to changes in patient
      management.

PMID- 15170879
TI  - PCD and RP: X-linked inheritance of both disorders?
AB  - A Caucasian, seven-generation family of Polish origin with apparently X-linked
      inheritance of coexisting retinitis pigmentosa (RP) and primary ciliary
      dyskinesia (PCD), with 14 identified males affected with RP and 14 obligate
      healthy female carriers, is presented. To our knowledge, four of the RP-affected
      males were diagnosed with PCD. The cases might imply the presence of one of the
      PCD loci, influencing neither laterality nor fertility, within the X-chromosome.

PMID- 15170882
TI  - The changing face of clinical trials.

PMID- 15170880
TI  - Comment on "Pediatric lymphocytic interstitial pneumonitis in an HIV-negative
      child with pulmonary Epstein-Barr virus infection".

PMID- 15170883
TI  - Smallpox vaccination recommendations for contacts of pediatric cancer patients.

PMID- 15170884
TI  - Treatment of pediatric Hodgkin disease avoiding radiotherapy: excellent outcome
      with the Rotterdam-HD-84-protocol.
AB  - BACKGROUND: To reduce radiotherapy (XRT) induced toxicity of treatment of
      children with Hodgkin disease (HD) while maintaining a high cure rate, we
      introduced a risk-adapted protocol consisting of chemotherapy (CT) alone in 1984.
      PROCEDURE: The outcome of 46 children treated for HD from 1984 until 2000
      according to the Rotterdam-HD-84-protocol was determined. Children with stage I
      IIA disease (n = 23), were treated with six courses of epirubicin, bleomycin,
      vinblastine, and dacarbazine (EBVD). Children with stage IIB-IV disease (n = 23),
      were treated with three to five alternating cycles of EBVD and mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP). RESULTS: At a median follow-up
      time of 8.6 years (range 2.6-18.3 years), the 10-year overall survival (OS) is
      95% and the event-free survival (EFS) 91%. In 5/46 patients XRT was administered
      because of residual mediastinal mass. Four children relapsed, two of them died.
      Up until now only one patient developed hypothyroidism; no symptomatic cardiac or
      pulmonary dysfunction, no second malignancy has been diagnosed. CONCLUSIONS: Risk
      adapted treatment consisting of CT alone is highly efficacious for children with
      HD and toxicity is low. XRT was administered in only a small minority of children
      with HD. CT should be the first choice for HD in children and XRT should
      preferably be used for those with refractory or histologically proven residual
      disease or relapse.

PMID- 15170885
TI  - High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of
      relation between serum methotrexate concentration and creatinine clearance.
AB  - BACKGROUND: The objectives of this study were: (1) to analyze the relation of
      serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare
      the leucovorin rescue dose administered to the patients based on creatinine
      clearance, with the one calculated according to serum MTX levels, and (3) to
      determine MTX-related toxicity. PROCEDURE: Thirty children with high-risk non-B
      acute lymphoblastic leukemia (ALL) treated according to the national protocol
      (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with
      four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals
      (group M1 and M2, respectively). Serum MTX concentrations were measured at 24,
      42, and 48 hr after beginning the infusion and were analyzed retrospectively. The
      creatinine clearance was calculated after 12-hr intravenous hydration prior to
      each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance.
      RESULTS: Serum MTX concentrations at 24, 42, and 48 hr after starting the
      infusion were not related to creatinine clearance in both treatment groups.
      Leucovorin rescue administered according to creatinine clearance was excessive in
      43% in group M1 and in 51% in group M2, as compared to the dose calculated
      according to serum MTX levels. No serious clinical complications were observed.
      CONCLUSIONS: These results suggest that creatinine clearance is not a good
      parameter to calculate leucovorin rescue. MTX-related toxicity in this group of
      patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without
      monitoring serum MTX levels was acceptable.

PMID- 15170887
TI  - Ewing sarcoma: favourable results with combined modality therapy and conservative
      use of radiotherapy.
AB  - BACKGROUND: At the Hospital for Sick Children (HSC), we have treated Ewing
      sarcoma (ES) with multi-agent chemotherapy, surgery and conservative use of
      radiotherapy for local control. Our objective was to describe the outcome and
      prognostic factors associated with this strategy. PROCEDURE: We performed a
      retrospective chart review of children diagnosed with ES at HSC from Feb 1984 to
      June 1999. RESULTS: Seventy-two evaluable children were identified. All received
      chemotherapy. Local control administered was surgery (n = 37), radiation (n =
      23), both (n = 10) or neither (n = 2). The 7-year EFS was 66.4%. Recurrence
      occurred in 23 patients, 7 locally and 16 distantly. Better EFS was associated
      with male gender (78.5% vs. 52.1%; P = 0.007), localised disease (77.0% vs.
      39.4%; P = 0.0004), extremity primary (88.2% vs. 52.8%; P = 0.005) and non-pelvic
      primary (75.7% vs. 18.2%; P < 0.0001). CONCLUSIONS: Favourable outcomes were seen
      for patients treated with multi-agent chemotherapy, surgery and conservative use
      of radiotherapy. Metastatic disease rather than local control was the major cause
      of failure.

PMID- 15170886
TI  - Functional and molecular characterization of interleukin-2 transgenic Ewing tumor
      cells for in vivo immunotherapy.
AB  - BACKGROUND: Interleukin-2 (IL-2) is a potent cytokine with potential activity
      against several tumors including Ewing tumors (ET). Side effects of systemic IL-2
      can be circumvented by the use of transgenic tumor cells. However, in vitro
      manipulation may change the overall gene expression profile of tumor cells
      unfavorably. Therefore, we assessed gene expression profiles, safety, and
      immunomodulatory efficacy of IL-2 transgenic (IL-2-tg) ET cells in vitro and in
      NOD/scid mice. PROCEDURE: Viable wild type A673 tumor cells were co-cultured
      together with irradiated IL-2-tg or mock-transfected cells and HLA matched
      peripheral blood mononuclear cells. Activation of T and NK cells was assessed by
      FACS analysis. The effect of irradiated IL-2-tg cells on tumor growth in vivo was
      investigated by using NOD/scid mice. Gene expression profiles of wild type and
      transfected cells were analyzed with Affymetrix HG-U95A microarrays. RESULTS: IL
      2-tg cells activated and increased the number of T cells and NK cells in vitro.
      Co-culture with IL-2-tg but not with mock-transfected cells almost completely
      suppressed wild type tumor cell growth in vitro. Cell depletion experiments
      indicated a major contribution of NK cells to this tumor cell suppression. Co
      transfer of irradiated IL-2-tg cells significantly reduced wild type tumor growth
      in NOD/scid mice. Side effects in the treated animals were not observed and no
      tumor growth was observed after injection of irradiated IL-2-tg cells alone. Gene
      expression profiling revealed a substantial degree of homogeneity of gene
      expression in transfected and wild type cells and suggests that transfection and
      selection procedures had no major impact on the gene expression profile.
      CONCLUSIONS: Next to a high degree of homogeneity between transgenic and wild
      type cells, our data suggest that irradiated IL-2-tg ET cells can activate
      cytolytic effector cells. These cells may have therapeutic potential for ET
      patients.

PMID- 15170888
TI  - Surgery of cavoatrial tumor thrombus in nephroblastoma: a report of the SIOP/GPOH
      study.
AB  - BACKGROUND: Resection of a Wilms tumor extending through the inferior vena cava
      into the right atrium represents a challenge to the pediatric surgeon. Exact
      preoperative diagnosis is essential to identify the tumor and its intravascular
      extension. To achieve a complete excision of the tumor cardiopulmonary bypass and
      hypothermia may be required. The feasibility of a complete resection is important
      as it guides subsequent therapy such as chemotherapy and radiation. PROCEDURE: In
      order to define these issues, we reviewed the records of 33 of 1,151. Patients
      enrolled in the SIOP 93-01/GPOH Study and the SIOP 2001/GPOH Study who had a
      tumor thrombus into the inferior vena cava and into the right atrium. RESULTS:
      The median age at diagnosis was 3.73 years. Twenty-four patients had a tumor
      thrombus into the inferior vena cava, in nine patients the thrombus reached into
      the right atrium. All patients were operated on; cardiopulmonary bypass was used
      in nine patients. There were no deaths intraoperatively. Twenty-nine children are
      still alive; four patients died, one patient due to aspiration and failed
      resuscitation, two patients died from a recurrent tumor, and one child due to an
      unresectable primary tumor. CONCLUSION: Our report suggests that Wilms tumor
      extending to the inferior vena cava and the right atrium is technical
      challenging, but with adequate preoperative diagnosis and a multidisciplinary
      surgical approach including cardiopulmonary bypass and hypothermia, the prognosis
      is favorable.

PMID- 15170889
TI  - Differential responsiveness among "high risk" pediatric brain tumors in a pilot
      study of dose-intensive induction chemotherapy.
AB  - BACKGROUND: These factors have been predictive for progressive disease on therapy
      (PDOT) among pediatric brain tumors: >1.5 cm(2) unresectable tumor, glioblastoma,
      supratentorial primitive neuroectodermal tumor, and metastatic medulloblastoma
      (MBL). This pilot study sought to correlate cytoreductive response with
      progression free survival. PROCEDURES: Four courses of cisplatinum,
      cyclophosphamide, etoposide, and vincristine preceded hyperfractionated
      radiotherapy (RT). Maintenance chemotherapy consisted of eight cycles of
      carboplatin, etoposide, and vincristine. Biopsy specimens were
      immunohistochemically studied for labeling index, hypoxia, and multidrug
      resistance proteins. RESULTS: Twenty newly diagnosed patients [nine primitive
      neuroectodermal tumors/MBL, one choroid plexus carcinoma, eight malignant
      gliomas, and two anaplastic ependymomas] were treated. Ten patients, who required
      neuraxis irradiation, constituted the "PNET" group. These demonstrated five
      complete and one partial response (PR), with an estimated median progression free
      survival of 44 months and median survival in excess of 53 months. Patients
      treated with involved field irradiation were designated the "Glioma" group.
      Induction chemotherapy produced partial and minor responses (MRs) among 5/10.
      Their estimated median progression free survival was 6.9 months (P = 0.035
      relative to the PNET) with a median survival of 10.7 months (P = 0.04). Age,
      labeling index, the presence of hypoxia, and Pgp/MDR1 expression failed to
      discriminate between the two groups. CONCLUSIONS: This induction regimen produced
      a cytoreductive response in 6/10 and achieved a significant improvement in
      progression free survival among 7/10 in the PNET group. Unfortunately, responses
      among Glioma patients did not translate into durable control. Expression of the
      biologic factors was similar between both groups and did not correlate with
      diagnosis or response.

PMID- 15170890
TI  - Retinoic acid therapy in "degenerative-like" neuro-langerhans cell histiocytosis:
      a prospective pilot study.
AB  - BACKGROUND: Degenerative-like neuro-Langerhans cell histiocytosis (DN-LCH) is a
      rare complication of LCH marked by progressive cerebellar ataxia. No treatment
      has so far been shown to slow this progression. PROCEDURE: All-trans retinoic
      acid (ATRA) was administered orally at a dose of 45 mg/m(2) daily for 6 weeks and
      then 2 weeks every month for 1 year. The endpoints were clinical status at 1 year
      (assessed with rating scales for ataxia and disability), adverse effects, and
      changes in neurological abnormalities on MRI. RESULTS: Ten patients were studied.
      The treatment was well tolerated. All the patients were clinically stable at the
      end of the study. No MRI changes were noted. CONCLUSIONS: DN-LCH appeared to be
      stable during ATRA therapy, but further studies are required to appreciate the
      possible long-term benefits of ATRA.

PMID- 15170891
TI  - Course and clinical impact of magnetic resonance imaging findings in diabetes
      insipidus associated with Langerhans cell histiocytosis.
AB  - BACKGROUND: Diabetes insipidus (DI) is the most frequent sequela in Langerhans
      cell histiocytosis (LCH). The clinical relevance and therapeutic impact of brain
      magnetic resonance imaging (MRI) findings in LCH patients with LCH during the
      disease course is unclear. PROCEDURE: In this retrospective study, we reviewed
      113 brain MRIs from 59 DI patients, in 17 of these serial follow up MR
      examination findings were correlated to the clinical course and therapy. RESULTS:
      At DI diagnosis, 71% patients showed a thickened stalk, in 24% the stalk was
      still thickened on MRIs done more than 5 years after DI onset, and in two
      patients the stalk was already thickened several months before DI onset. The
      changes of the pituitary stalk thickness were highly variable and did not clearly
      correlate with the treatment. Regression of pituitary thickness on MRI did not
      concur with clinical recovery of DI, which persisted in all but one patient with
      initially partial DI. The occurrence of anterior pituitary hormone deficiencies
      appeared to be linked to a thickening of the stalk at DI diagnosis. LCH-lesions
      in the craniofacial bones were seen in 75% DI patients, and 76% of DI patients
      with follow up MRIs done 5 years or longer after DI diagnosis had parenchymal
      neurodegenerative brain changes. CONCLUSIONS: Our study indicates that repeated
      MR-examinations in DI patients are of limited value for assessing a response to
      therapy in the pituitary stalk, but are important for the monitoring of
      craniofacial bone lesions and for the detection of parenchymal CNS disease.

PMID- 15170892
TI  - CD19 negative precursor B acute lymphoblastic leukemia presenting with
      hypercalcemia.
AB  - A 9-month-old infant presented with hypercalcemia and lytic bone lesions.
      Suspicion for malignancy led to a bone marrow examination, which showed
      replacement of the marrow by a small round blue cell infiltrate. Flow cytometric
      analysis of these cells showed an unusual immunophenotype in that these cells
      were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34
      negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy
      chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic
      leukemia (ALL). He received supportive treatment with hydration and pamidronate,
      but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL
      was established, the patient was treated with an infantile ALL chemotherapeutic
      regimen and the hypercalcemia resolved. This case highlights the usefulness of
      immunoglobulin gene rearrangement studies in atypical cases of ALL.

PMID- 15170893
TI  - Favorable response to soft tissue sarcoma therapy in an adolescent with embryonal
      renal sarcoma.
AB  - Embryonal renal sarcomas were first identified in 1995 among banked tumor samples
      originally classified as adult Wilms tumor. Few long-term remissions were
      observed when these rare tumors were treated with chemotherapy usually used for
      childhood Wilms. Data were collected from the medical record of an adolescent
      female with embryonal renal sarcoma and treated with sarcoma-directed
      chemotherapy and radiation. At 66 months following diagnosis, the patient has no
      evidence of tumor but has experienced severe renal dysfunction and ovarian
      failure. We believe there is a subset of patients with disseminated embryonal
      renal sarcoma that respond to intense sarcoma-directed therapy.

PMID- 15170894
TI  - Patients with primary brain tumors as organ donors: case report and review of the
      literature.
AB  - Malignancy is considered a contra-indication to organ donation, with a few
      possible exceptions. We present the case of a child with fatal intracranial
      hemorrhage from a primary brain tumor (PBT) whose organs were denied for
      transplant after recovery. We review the literature of organ donors with PBTs in
      the context of the current organ shortage and discuss the implications for the
      practicing oncologist. Transmission of donor brain tumor to organ recipients has
      been documented but the incidence appears to be very low. Risk factors for tumor
      transmission include underlying donor tumor histology, history of craniotomy
      and/or shunt placement, use of systemic chemotherapy and radiation therapy, and
      duration of disease prior to donation. Ongoing data collection by national
      registries will provide more information on the potential risk to organ
      recipients. It may be appropriate to expand the donor pool to include donors with
      PBTs in certain situations. The transplantation team ultimately decides upon the
      use of organs from specific donors. Many families will appreciate the opportunity
      to donate specific tissues even if solid organ transplantation is prohibited.

PMID- 15170895
TI  - Intratumoral methotrexate kinetics in a patient with intracranial anaplastic
      ependymoma.
AB  - Little is known about intratumoral anticancer drug concentration in childhood
      brain tumors. We were able to measure methotrexate (MTX) tumor concentrations
      directly in a cystic anaplastic ependymoma. Cyst fluid was obtained by puncture
      of a subgaleal Rickham reservoir connected to a catheter in the tumor cyst. MTX
      concentrations were determined by fluorescence polarization immunoassay and
      compared to serum concentrations. Maximum MTX concentrations in tumor and CSF
      were found at the end of MTX infusion. Twenty-four hour after MTX infusion the
      mean tumor concentration was significantly higher than in the serum indicating
      MTX retention and accumulation in the tumor cyst. An AUC(tumor)/AUC(serum) ratio
      of 1.95 was obtained. In response to the applied multiagent chemotherapy the
      clinical condition of our patient improved and the tumor showed partial response
      on MRI. Cystic ependymomas might benefit from high dose MTX especially because of
      drug retention in the tumor cyst.

PMID- 15170897
TI  - Mondini dysplasia and recurrent bacterial meningitis in a girl with relapsing
      Langerhans cell histiocytosis.
AB  - We report a case of a girl with Langerhans cell histiocytosis (LCH) of multifocal
      bone disease, who developed recurrent bacterial meningitis and unilateral
      sensorineural hearing loss during the relapsing course of the disease. Mondini
      dysplasia, a congenital inner ear anomaly, was suspected by high resolution
      computed tomographic scan and the dysplasia with cerebrospinal fluid leakage was
      confirmed by surgery in the ipsilateral ear showing hearing loss. Although rare,
      congenital inner ear anomalies such as Mondini dysplasia should be kept in mind
      in pediatric patients with hearing impairment and/or recurrent bacterial
      meningitis during chemotherapy for various types of neoplasms including LCH.

PMID- 15170896
TI  - Efficacy of continuous infusion 2-CDA (cladribine) in pediatric patients with
      Langerhans cell histiocytosis.
AB  - Patients with Langerhans cell histiocytosis (LCH) may behave differently
      depending on what sites are involved and the response or lack of response to
      earlier therapies. Therapy for high-risk patients or those with multiple
      reactivations continues to be challenging because of variable response rates and
      frequent toxicities. The goals of this study were to determine the long-term
      disease free survival in children with high-risk or multiply reactivated LCH
      treated with 2-CDA, and the toxicity of low dose continuous infusion (CI). Ten
      children with multiple reactivations or high-risk disease as defined by the
      Histiocyte Society were treated with CI 2-CDA and were evaluable for response and
      toxicity assessment. The starting dose of 2-CDA was 5 mg/M(2)/day for 3 days and
      escalated to 6.5 mg/M(2)/day for 3 days if tolerated. The maximum number of
      courses of 2-CDA per patient was limited to six. Fifty-two courses of 2-CDA were
      administered without difficulty. After the patient demonstrated no acute toxicity
      with the first administration of 2-CDA, the subsequent doses were given at home
      to all but one patient. All 10 patients had a clinical response, 9 documented by
      radiographic, or changes in physical exam or review of systems. Toxicity was
      limited to myelosuppression. Seven of the 10 patients required no additional
      therapy and remain disease free a median of 50 months from completing therapy.
      The three remaining patients are currently disease free after receiving other
      therapy. Further studies are needed to determine the role of 2-CDA in this
      patient population. 2-CDA can be given safely using home therapy, and may
      effective even in high-risk patients.

PMID- 15170898
TI  - Oral health of long-term childhood cancer survivors.

PMID- 15170899
TI  - Boerhaave syndrome following chemotherapy in a child with acute lymphoblastic
      leukemia.

PMID- 15170900
TI  - Re: Imashuku et al. Pineal dysfunction (low melatonin production) as a cause of
      sudden death in a long-term survivor of Langerhans cell histiocytosis? Med
      Pediatr Oncol 2003;41:151-153.

PMID- 15170904
TI  - Leflunomide: a manageable safety profile.
AB  - The safety profile of leflunomide in the treatment of rheumatoid arthritis has
      been well documented in clinical trials, postmarketing surveillance, and
      epidemiological studies. Both postmarketing surveillance and epidemiological
      study results are consistent with the safety profile of leflunomide reported in
      clinical trials, and no increased risk was observed with leflunomide, compared
      with other disease modifying antirheumatic drugs; these studies have allowed a
      more precise representation of the incidence of adverse events occurring with
      leflunomide under normal conditions of care. The most common leflunomide
      associated adverse events include diarrhea, elevated liver enzymes, alopecia, and
      rash. Ninety-five percent of the Expert Panel considered the adverse events
      associated with leflunomide to be manageable. If an adverse event required
      treatment to be stopped, many of the experts would consider subsequently
      restarting leflunomide. For minor adverse events, it was suggested that the
      physician might also consider using cholestyramine or charcoal to determine if
      the side effect is dose-related and, if it was, reduce the leflunomide dose
      accordingly. In addition to informing patients about the likelihood of side
      effects, it is important to emphasize that their incidence appears to diminish
      with continued treatment. It is also important to adequately support patients who
      are experiencing side effects and involve them in their disease management, for
      example, by offering the choice of reducing the leflunomide dose and/or having
      symptomatic treatment. Other patient management recommendations in this review
      reflect the views of the majority of participants as expressed in the meeting.

PMID- 15170903
TI  - The efficacy of leflunomide monotherapy in rheumatoid arthritis: towards the
      goals of disease modifying antirheumatic drug therapy.
AB  - This expert review of results from the leflunomide phase II and III clinical
      trials database demonstrates that leflunomide meets all 3 goals desired of
      disease modifying antirheumatic drug (DMARD) therapy: reducing the signs and
      symptoms of the disease; inhibiting structural damage; and improving physical
      function. Further, leflunomide has a rapid onset of action, sustained efficacy,
      and is effective in early and late disease, regardless of whether patients have
      received other DMARD previously. The consistent efficacy of leflunomide across
      phase III clinical trials is confirmed by the findings from clinical practice.
      Experts agreed that it is important to observe a patient under leflunomide
      monotherapy for at least 3-4 months before assessing efficacy. It is possible to
      start maintenance therapy, with either a daily dose of leflunomide 10 mg,
      subsequently changing to 20 mg, or the reverse. The decision to use a loading
      dose when initiating leflunomide therapy depends primarily on the balance between
      the tolerability and rapid efficacy associated with a loading dose, and the
      balance desired for an individual patient. In general, the use of both
      maintenance and loading doses requires a flexible approach to the treatment of
      rheumatoid arthritis. During the first few weeks of leflunomide therapy, patient
      dropout can be avoided by using prednisolone rather than a loading dose.
      Moreover, to ensure good tolerability and compliance in patients receiving a
      loading dose, information and adequate support should be provided throughout
      treatment.

PMID- 15170906
TI  - Dose-dependent severe arthralgia induced by gabapentin.

PMID- 15170905
TI  - Lefunomide in combination therapy.
AB  - In most studies of disease modifying antirheumatic drug therapy, in combination
      with either leflunomide or biological agents, patients are given an additional
      agent after they have failed treatment with methotrexate (MTX). This review of
      clinical studies shows that leflunomide is clinically efficacious and well
      tolerated when added to either sulfasalazine or MTX, as both an initial and
      ongoing treatment for rheumatoid arthritis (RA). Experience in combining
      leflunomide with biological agents is limited to a small number of open-label
      studies with infliximab. According to the opinion obtained at an International
      Expert Panel Meeting held in Paris in May 2003, leflunomide can be used in
      combination therapy: 61% of the Expert Panel would use leflunomide with MTX, 71%
      with sulfasalazine, 43% with infliximab, 33% with adalimumab, 19% with
      etanercept, and 38% with anakinra. The Expert Panel stated that the combination
      of leflunomide and infliximab warrants a prospective, randomized, controlled
      trial in patients with incomplete clinical responses to leflunomide monotherapy,
      provided leflunomide is started first, without a loading dose, and infliximab is
      added after good tolerability to leflunomide has been established. The Expert
      Panel concluded that combination therapy with leflunomide has a place in the
      treatment of RA. Caution is advised, however, when using combination treatments
      and, therefore, the patient's safety should be carefully monitored.

PMID- 15170907
TI  - Is there a rationale for switching from one anti-tumor necrosis factor agent to
      another?

PMID- 15170908
TI  - Rheumatoid arthritis: is the disease becoming milder or is treatment improving?

PMID- 15170909
TI  - Measuring patient health status in rheumatoid arthritis -- what is a minimal
      clinically important difference?

PMID- 15170910
TI  - What I would like to know about leflunomide.

PMID- 15170912
TI  - Hypertension, NSAID, and lessons learned.

PMID- 15170911
TI  - Coping with chronic pain: what can we learn from pain self-efficacy beliefs?

PMID- 15170913
TI  - Activation of synovial cell p38 MAP kinase by macrophage migration inhibitory
      factor.
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory
      cytokine important in animal models of rheumatoid arthritis (RA). We investigated
      the utilization by MIF of mitogen activated protein (MAP) kinase signalling
      pathways in the stimulation of fibroblast-like synoviocytes (FLS), cyclooxygenase
      2 (COX-2), prostaglandin E(2) (PGE(2)), and interleukin 6 (IL-6) and IL-8
      expression. METHODS: Cultured human RA FLS were treated with recombinant MIF.
      Activation of MAPK was measured by Western blotting and blocked using specific
      inhibitors. The expression of COX-2, PGE(2), IL-6, and IL-8 were measured using
      flow cytometry, ELISA, and real-time polymerase chain reaction. RESULTS: MIF
      induced the phosphorylation of FLS p38 and extracellular-signal regulated kinase
      (ERK) MAP kinase. MIF significantly induced COX-2 and IL-6 protein and mRNA
      expression as well as PGE(2) and IL-8 production. Antagonism of p38 MAP kinase
      inhibited MIF induction of COX-2, PGE(2), and IL-6. In contrast, antagonism of
      ERK had no effect on COX-2, PGE(2), or IL-6. Neither antagonist inhibited MIF
      induced IL-8. CONCLUSION: MIF activates RA FLS COX-2 and IL-6 expression via p38
      MAP kinase activation and induces IL-8 via p38 and ERK MAP kinase-independent
      pathways.

PMID- 15170915
TI  - Radiographic hand joint space width assessed by computer is a sensitive measure
      of change in early rheumatoid arthritis.
AB  - OBJECTIVE: To compare changes in the computerized measurement of radiographic
      hand joint space width (JSW) to changes in modified Sharp scores in a
      retrospective 2-year study of early rheumatoid arthritis (RA). METHODS: First and
      last standard clinical hand radiographs of 245 patients with RA were analyzed
      blind using purpose-written computer software to measure changes in JSW for
      proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in the 3
      middle fingers of each hand. Before measurement, the radiographs were scored
      independently by 2 radiologists using a modification of Sharp scoring. RESULTS:
      The paired changes in JSW (-0.051 +/- 0.005 mm) and Sharp score (+3.81 +/- 0.50)
      were both significant over the study duration. In measured joints showing an
      increase in joint space narrowing (JSN) score, 92% had a corresponding reduction
      in JSW. In patients with an increase in total score, including JSN and erosion
      scores in fingers and wrists, 84% had a corresponding reduction in mean (PIP +
      MCP) JSW. Patients with no change in Sharp score (47%) still experienced a
      significant reduction in measured JSW (-0.027 +/- 0.006 mm). HLA-DR genetic
      markers of severe disease progression were associated with significantly greater
      reductions in JSW but not increases in Sharp score. ( VALUES: mean +/- standard
      error of mean). CONCLUSION: Measured JSW averaged over 6 PIP and 6 MCP joints was
      a valid and more sensitive measure of change than total Sharp score in this study
      of early RA.

PMID- 15170914
TI  - Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor
      alpha production, in synovial tissues of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the significance of tristetraprolin (TTP) gene expression
      in synovial tissues of patients with rheumatoid arthritis (RA). METHODS: Gene
      expression was examined in synovial tissue and peripheral blood lymphocytes of a
      patient with RA by differential display-polymerase chain reaction (PCR). One of
      the identified genes, TTP, was selected for further analysis. cDNA was prepared
      from synovial tissues of 22 patients with RA and 22 with osteoarthritis (OA).
      Expression of TTP and tumor necrosis factor-a (TNF-a) genes was measured by
      TaqMan real-time semiquantification PCR. In RA samples, expression of TTP mRNA
      was compared with TNF-a mRNA, C-reactive protein (CRP), erythrocyte sedimentation
      rate (ESR), and steroid and/or disease modifying antirheumatic drug use. RESULTS:
      Expression of TTP gene was significantly higher in synovial tissues of RA
      patients than in OA. There was no apparent relationship between expression of TTP
      and TNF-a genes. TTP gene expression had a tendency to be inversely correlated
      with serum CRP, measured immediately before surgery. In addition, CRP was higher
      in patients with a low TTP/TNF-a gene expression ratio (p = 0.0071, Spearman rank
      correlation). CONCLUSION: A low TTP/TNF-a gene expression ratio could indicate
      failure of RA patients to produce adequate amounts of TTP in response to
      increased TNF-a production. Inappropriate TTP production may be one factor that
      contributes to higher RA disease activity.

PMID- 15170916
TI  - Variability of precision in scoring radiographic abnormalities in rheumatoid
      arthritis by experienced readers.
AB  - OBJECTIVE: To determine the extent of precision and sources of variability among
      experts on scoring radiographic abnormalities in rheumatoid arthritis. METHODS:
      Radiographic scores from 6 datasets in which 2 or more readers had scored film
      sets were analyzed. Datasets included scores by 11 different readers, 6 of whom
      scored films by both the Larsen (global) and Sharp (composite) methods. Scores of
      each possible combination of 2 readers were compared in calculating the smallest
      detectable difference (SDD) on raw scores and on scores normalized for each
      individual reader (nSDD). Intraclass correlation (ICC), Pearson's r, and the
      correlation between differences in score and their mean scores were determined.
      Agreement on progression of radiographic damage scores was also examined.
      RESULTS: Variability among readers was greater than previous studies suggested.
      Agreement was better for intra- than interreader comparisons; average intrareader
      SDD was 24.4 for the composite method and 9.0 for the global. The larger SDD for
      the composite method reflect their greater range of possible scores. When
      normalized scores were used to adjust for the range difference, there was minimal
      difference in the SDD; nSDD was 10.1 for the composite method, 8.0 for the
      global. Interreader variability was larger: SDD of 53.7 for the composite method
      and 23.3 for the global; nSDD 12.9 and 14.4, respectively. ICC varied between
      0.465 and 0.999, with all but one value below 0.925 occurring in composite scores
      with a range below 100. Differences in repeated scores were frequently associated
      with the mean of those scores and this was greater for inter- than for
      intrareader comparisons. Agreement between progression scores showed a similar
      pattern. The SDD was better for intrareader comparisons and smaller for global
      scores: compare 13.7 (composite, intrareader) and 5.4 (global, intrareader) to
      18.1 (composite, interreader) and 8.7 (global, interreader). The ICC was lower
      for progression scores than for raw scores, averaging between 0.661 and 0.885.
      CONCLUSION: The variability in scoring radiographic abnormalities is considerable
      among this group of 11 expert readers. This has important implications for power
      calculations in comparison studies such as therapeutic trials and for cross-trial
      comparisons. The correlation between the difference in repeated scores and their
      means indicates systematic error (bias), which, if corrected, may improve the
      detection of treatment effects when using a responder-type analysis. These and
      other design and analysis issues are discussed.

PMID- 15170917
TI  - Radiographic progression is getting milder in patients with early rheumatoid
      arthritis. Results of 3 cohorts over 5 years.
AB  - OBJECTIVE: There is a common impression, rarely documented, that the outlook of
      patients with rheumatoid arthritis (RA) is different today compared to previous
      decades. We investigated the 5-year radiographic progression of 3 cohorts of
      patients with early RA enrolled in the 1980s and 1990s. METHODS: Patients with
      early RA were enrolled into 3 separate studies in 1983-85 (n = 58; Cohort A),
      1988-89 (n = 77; Cohort B), and 1995-96 (n = 62; Cohort C) at one rheumatology
      center; all were subsequently treated actively with disease-modifying
      antirheumatic drugs according to the "sawtooth strategy" to control inflammation,
      and monitored regularly to collect data for evaluation of longterm outcome.
      Evaluation over 5 years included disease activity measures and medications.
      Radiographs of hands and feet taken at baseline and at 2 and 5 years were
      analyzed by Larsen score (0-100). RESULTS: Larsen score increased by a median of
      12, 6, and 4 points by Year 5 in cohorts A, B, and C, respectively (p = 0.001),
      adjusted for age, sex, rheumatoid factor (+/-), and the baseline values for
      Larsen score and erythrocyte sedimentation rate. RF positivity and persistent
      high disease activity over 5 years were associated with greater progression of
      radiographic damage. CONCLUSION: Radiographic progression was greatest in the
      earliest cohort and mildest in the most recent cohort, a phenomenon that was also
      seen in the literature review. The reasons for the observation may include (1)
      improved therapy, (2) milder disease, and (3) patient selection.

PMID- 15170918
TI  - Effects of high dose methylprednisolone pulse therapy on bone mass and
      biochemical markers of bone metabolism in patients with active rheumatoid
      arthritis: a 12-month randomized prospective controlled study.
AB  - OBJECTIVE: To study the effects of one year of high dose 6-methylprednisolone
      pulse therapy (MPPT) on bone mass, seric bone alkaline phosphatase (sBAP), and
      urinary deoxypyridinoline (uDpyr) in patients with active rheumatoid arthritis
      (RA), and to compare results with those of patients with active RA treated with
      oral methylprednisolone (OMP). METHODS: Thirty-one women with active RA were
      given 1000 mg of MP IV for 3 alternate days, with a mean interval of
      administration of 76 days (+/- 8.3 SD) for one year (MPPT group). Bone mineral
      density (BMD) (total body, lumbar spine, and femur neck), plasma levels of sBAP,
      and urinary concentrations of uDpyr were assessed at the beginning of the
      treatment and every 3 months until the end of the study. Moreover, erythrocyte
      sedimentation rate (ESR), Thompson joint score, and early morning stiffness were
      assessed at study entry and every month. The control group, 31 women with active
      RA treated with oral MP, was followed in the same way (OMP group). RESULTS: In
      the MPPT group there was no significant reduction of BMD at any site compared to
      significant reductions in lumbar BMD at 6 and 12 months and total body BMD and
      femur neck BMD at 12 months in the OMP group. Also in the OMP group, a
      significant reduction in the mean sBAP was observed. The mean uDpyr levels were
      not significantly reduced in either group. CONCLUSION: Our results show that
      MPPT, compared to continuous therapy with oral corticosteroids, preserves bone
      mass without modifying the biochemical markers of bone metabolism.

PMID- 15170919
TI  - Progression of rheumatoid arthritis on plain radiographs judged differently by
      expert radiologists and rheumatologists.
AB  - OBJECTIVE: In a former study a panel of rheumatologists was used to assess which
      progression in radiological joint damage due to rheumatoid arthritis (RA) on hand
      and foot radiographs taken at one-year intervals was considered the minimally
      clinically important difference (MCID). We compare the judgments of the panel of
      rheumatologists with the judgments of 2 musculoskeletal radiologists. METHODS:
      Two experienced musculoskeletal radiologists evaluated independently the same
      hand and foot radiographs as assessed by the panel of rheumatologists.
      Progression was defined as important if the radiologist would state it as
      substantial progression in their report. Two readers, different from the
      radiologists and rheumatologists, independently obtained the Sharp/van der Heijde
      scores. Receiver operating characteristic curve analyses were performed to
      quantify the minimally important progression defined by the radiologists
      expressed in Sharp/van der Heijde change-scores. The change-score with the
      highest accuracy represented the minimally important progression and was compared
      with the MCID defined by the panel of rheumatologists for 4 different settings
      (early versus advanced RA and mild versus high disease activity). RESULTS: The
      minimally important progression defined by the radiologists was estimated at 6.5
      Sharp/van der Heijde units. This was larger than the MCID defined by the panel of
      rheumatologists in 3 of the 4 clinical settings (3.0-4.5 units) and similar to
      the setting "advanced RA, mild disease activity." The panel of rheumatologists
      was inclined to change therapy in cases not reported as substantially progressive
      by the radiologists. The Sharp/van der Heijde progression scores of the
      radiographs on which the radiologists and rheumatologists disagreed related
      better with the rheumatologists' opinions. CONCLUSION: Changes that were not
      regarded as substantial by the radiologists were judged clinically important by
      the rheumatologists in 3 of the 4 clinical settings. Thus, the radiologists
      appeared to be reserved in judging changes as important.

PMID- 15170920
TI  - High sensitivity C-reactive protein as a disease activity marker in rheumatoid
      arthritis.
AB  - OBJECTIVE: To elucidate the potential contribution of high sensitivity C-reactive
      protein (hs-CRP) testing in the assessment of disease activity in rheumatoid
      arthritis (RA). METHODS: We recorded clinical and psychological variables, the hs
      CRP, and erythrocyte sedimentation rate (ESR) in 146 consecutive patients with
      RA. We analyzed the associations between the ESR and hs-CRP versus the other
      recorded variables. RESULTS: The median (interquartile range) ESR (mm/h) and hs
      CRP (mg/l) were 15 (7-36) and 5 (2.3-13.9), respectively. Thirty-two (22%)
      patients had an hs-CRP < 2 mg/l, 61 (42%) an hs-CRP of 2-8 mg/l and 53 (36%) an
      hs-CRP > 8 mg/l. In patients with an hs-CRP of 2-8 mg/l, the swollen joint counts
      and the physician disease activity scales were higher, and remission rates were
      lower than in patients with an hs-CRP of < 2 mg/l. The hs-CRP was consistently
      more closely associated with disease activity, depression, and helplessness than
      was the ESR. CONCLUSION: High sensitivity CRP testing reveals systemic
      inflammation that is generally not detectable with routine CRP assays and that is
      associated with disease activity in RA.

PMID- 15170921
TI  - The efficacy of switching from etanercept to infliximab in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To describe the degree of clinical benefit in patients with rheumatoid
      arthritis (RA) who receive infliximab therapy after lack of efficacy with
      etanercept. METHODS: In a retrospective study among 6 centers primarily designed
      to assess the safety of infliximab in combination with leflunomide, a
      standardized chart review form was used to collect data on 93 patients with RA.
      During that study, it was noted that some of these patients had switched from
      etanercept to infliximab. In this study, we compared the response of subjects
      switching from etanercept to infliximab (n = 20) to that of subjects receiving
      infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS:
      The swollen and tender joint count, patient and physician global assessments,
      morning stiffness, and C-reactive protein all improved substantially in both
      groups, with no statistical difference in the degree of benefit between the
      groups. At the time of chart review, switchers had received a statistically
      higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a
      total of 5.7 and 5 infusions, respectively. CONCLUSION: In this retrospective
      study, previous lack of efficacy with etanercept did not predict lack of efficacy
      with infliximab. Indeed, the degree of clinical improvement was similar in both
      groups, although switchers were receiving a higher dose of infliximab at the time
      of chart review. Our findings suggest that clinical response may differ between
      anti-TNF agents, and lack of response to one agent may not predict a lack of
      response to another.

PMID- 15170923
TI  - Comparative study of serum surfactant protein-D and KL-6 concentrations in
      patients with systemic sclerosis as markers for monitoring the activity of
      pulmonary fibrosis.
AB  - OBJECTIVE: To clarify the clinical significance of surfactant protein-D (SP-D)
      and KL-6 in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients
      with systemic sclerosis (SSc), and to evaluate the differences between SP-D and
      KL-6. METHODS: Serum SP-D and KL-6 concentrations were determined by ELISA in 42
      SSc patients. In a retrospective longitudinal study, 83 serum samples from 6 SSc
      patients were analyzed during a followup period of 0.6-6.3 years. RESULTS: SP-D
      and KL-6 concentrations at the first visit were higher in patients with SSc,
      especially those with PF, compared with healthy controls. Increased
      concentrations of SP-D were associated with decreased DLCO and decreased vital
      capacity in SSc patients more strongly than those of KL-6. The sensitivity and
      specificity for PF were 91% and 88% for SP-D and 39% and 100% for KL-6,
      respectively. In the longitudinal study, both SP-D and KL-6 concentrations were
      associated with activity of PF in patients with SSc. SP-D concentrations changed
      more rapidly than KL-6 concentrations, in parallel with the PF activity.
      CONCLUSION: SP-D was a more sensitive marker for PF than KL-6. By contrast, KL-6
      showed higher specificity than SP-D. Combined use of these 2 serum markers would
      be more helpful to diagnose and monitor the PF activity in patients with SSc than
      single use of each marker.

PMID- 15170922
TI  - Effects of anakinra monotherapy on joint damage in patients with rheumatoid
      arthritis. Extension of a 24-week randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine the effects of treatment on the radiologic manifestations
      of joint damage in patients with rheumatoid arthritis (RA) who participated in a
      24-week extension study of a randomized, placebo-controlled clinical trial of
      anakinra, a recombinant human interleukin 1 receptor antagonist. METHODS: The
      patients had entered a 24-week, randomized, double-blind, placebo-controlled
      study. Anakinra was self-administered by subcutaneous injection of 30, 75, or 150
      mg/day. Upon completion of the placebo-controlled phase, the patients entering
      the extension study who had received placebo were randomized to one of the 3
      treatment dosages for a further 24 weeks, and the patients who had been initially
      randomized to one of the 3 anakinra dosages continued to receive the same dosage.
      Radiographs of the hands were obtained at baseline and at 24 and 48 weeks. The
      radiographs were evaluated using a modified Sharp method. RESULTS: A total of 472
      patients were recruited. The mean change in the total modified Sharp score of 178
      patients who completed 48 weeks treatment, including all dosages, was
      significantly less than the change observed in 58 patients who received placebo
      for 24 weeks and anakinra for 24 weeks (p = 0.015). A significant reduction in
      the change of the total modified Sharp score was observed in the patients who
      received anakinra 75 and 150 mg/day. The total modified Sharp score was reduced
      significantly more during the second 24-week treatment period, compared to the
      first (p < 0.001). Significant reductions in the second 24-week period were
      observed following anakinra 75 mg/day (p = 0.006) and 150 mg/day (p = 0.008).
      CONCLUSION: Patients with RA who received anakinra for 48 weeks demonstrated
      significant slowing of radiographic joint damage. The treatment effect observed
      after the first 24-week period appeared to increase when anakinra was continued
      for 48 weeks.

PMID- 15170924
TI  - Centromere protein C is a target of autoantibodies in Sjogren's syndrome and is
      uniformly associated with antibodies to Ro and La.
AB  - OBJECTIVE: To determine which centromere proteins are recognized in Sjogren's
      syndrome (SS) and whether antibodies recognizing centromere proteins (CENP) B and
      CENP C identify a specific serologic subset. METHODS: Sera from 47 patients with
      SS, 12 xerostomic controls without SS, and 12 healthy controls were studied. All
      47 patients met San Diego criteria for SS. Of these, 45 patients had primary SS
      and 2 had secondary SS with CREST. Sera were analyzed by immunoprecipitation of
      [35S] methionine-labeled Ro 52, La, and CENP B and C generated by coupled in
      vitro transcription/translation. Human salivary gland cells were also lysed and
      immunoprecipitated to determine antibody status against Ro 60. Serological and
      clinical profiles of patients recognizing CENP were defined. Proportions of sera
      recognizing CENP B, CENP C, Ro, or La across the 3 groups were compared using
      Fisher's exact test. RESULTS: Twenty-eight of 45 primary SS patients (62%)
      recognized Ro 52, and 24 patients (53%) recognized La. Ten of these 45 (22%) sera
      recognized CENP B or C. Furthermore, 7 of these 10 recognized exclusively CENP C;
      these 7 (100%) all tested positive for antibodies to both Ro 52 and La. This was
      in contrast to the group of SS patients that did not recognize CENP C alone, in
      whom anti-Ro 52 antibodies were found in 21 of 38 (55%; p = 0.034), and
      antibodies to La in 17 (45%; p = 0.01). Five of 7 CENP C positive sera were also
      positive for Ro 60. One of 3 patients with antibodies to CENP B also had
      antibodies to Ro 52, while none of these 3 had antibodies to La. Only patients
      with antibodies to CENP B showed a centromere pattern on immunofluorescence
      staining. CONCLUSION: Antibodies to both CENP B and CENP C occur in SS. In a
      subset representing 15% of SS patients studied, these anticentromere antibodies
      recognize exclusively CENP C, and were uniformly associated with antibodies to Ro
      52 and La.

PMID- 15170925
TI  - The clinical assessment of patients with psoriatic arthritis: results of a
      reliability study of the spondyloarthritis research consortium of Canada.
AB  - OBJECTIVES: To evaluate whether rheumatologists experienced in psoriatic
      arthritis (PsA) assess peripheral and axial involvement in the same way and to
      consider core clinical measurements that should be included in clinical trials in
      PsA. METHODS: Ten patients with PsA, representing a broad range of joint
      inflammation, joint damage, and spinal involvement, were selected for the study.
      Each patient was examined by each of 10 rheumatologists, members of the
      Spondyloarthritis Research Consortium of Canada, according to a Latin Square
      design. Assessments included scoring actively inflamed joints and damaged joints,
      dactylitis, enthesitis, and spinal measurements. Variance components analyses
      were conducted for continuous measurements based on models with observer,
      patient, and order effects. Estimates of intraclass correlation coefficients and
      associated 95% confidence intervals were obtained. RESULTS: There was substantial
      reliability in the assessment of the number of actively inflamed joints and
      excellent agreement in the number of damaged joints. Only moderate agreement was
      found for the number of digits with dactylitis. There was excellent agreement
      among observers in the intermalleolar distance measurements, but there was not as
      good agreement in the other measurements of spinal mobility. There was good
      agreement among the observers in detecting plantar fasciitis, however, the other
      entheses did not fare as well. CONCLUSION: In this first multicenter study of the
      assessment of clinical evaluation of patients with PsA we found that the
      assessment of peripheral joint disease is reliable although training should be
      performed prior to initiation of drug trials or comparative studies in this
      disease. The assessment of back measurements in PsA and other spondyloarthritis
      requires further study.

PMID- 15170927
TI  - Influence of Serum Amyloid A (SAA1) and SAA2 gene polymorphisms on renal
      amyloidosis, and on SAA/C-reactive protein values in patients with familial
      mediterranean fever in the Turkish population.
AB  - OBJECTIVE: To evaluate the effect of serum amyloid A (SAA) 1 and SAA2 gene
      polymorphisms on SAA levels and renal amyloidosis in Turkish patients with
      familial Mediterranean fever (FMF). METHODS: SAA1 and SAA2 gene polymorphisms and
      SAA levels were determined in 74 patients with FMF (39 female, 35 male; median
      age 11.5 yrs, range 1.0-23.0). All patients were on colchicine therapy. SAA1 and
      SAA2 gene polymorphisms were analyzed using polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP). SAA and C-reactive protein (CRP) values
      were measured and SAA/CRP values were calculated. RESULTS: The median SAA level
      was 75 ng/ml (range 10.2-1500). SAA1 gene polymorphisms were: a/a genotype in 23
      patients (31.1%), a/beta genotype in 30 patients (40.5%), a/g genotype in one
      patient (1.4 %), beta/beta genotype in 14 patients (18.9%), beta/g genotype in 5
      patients (6.8 %), and g/g genotype in one patient (1.4%). Of the 23 patients who
      had a/a genotype for the SAA1 polymorphism, 7 patients had developed renal
      amyloidosis (30.4%) compared to only one patient without this genotype (1/51;
      2.0%); p < 0.001. SAA2 had no effect on renal amyloidosis. SAA1 and SAA2
      genotypes had no significant effect on SAA levels. SAA/CRP values were
      significantly lower in patients with the SAA1a/a genotype, compared to other SAA1
      genotypes: 0.16 (0.025-1.96) versus 0.23 (0.012-28.20), p < 0.05. CONCLUSION:
      SAA1a/a genotype is one genetic factor that confers a significant risk for
      amyloidosis in the Turkish FMF population. Neither the SAA1 nor SAA2 genotypes
      had a significant effect on SAA level.

PMID- 15170926
TI  - Anti-interleukin 6 receptor antibody inhibits murine AA-amyloidosis.
AB  - OBJECTIVE: AA-amyloidosis is a severe complication in chronic inflammatory
      diseases. AA-amyloidosis is caused by the deposition of insoluble fibrils
      containing AA amyloid protein derived from serum amyloid A (SAA), which is
      synthesized by inflammatory cytokine stimulation. We examined whether anti
      interleukin 6 receptor (IL-6R) antibody prevented the development of AA
      amyloidosis in mouse models. METHODS: A transient model was induced by the
      injection of amyloid enhancing factor (AEF) and adjuvant treatment in C57BL/6
      mice. Monoclonal IgG1 antibody, MR16-1, was injected intraperitoneally just once
      before the injection of AEF and adjuvant. After 2 and 5 weeks, mice were
      sacrificed and histologically examined. In contrast, a chronic model was induced
      by AEF injection into IL-6 transgenic mice. One week later, in order to avoid
      neutralizing antibody production, MR16-1 (200 mg/kg) was injected intravenously.
      MR16-1 (5 mg/kg) was injected subcutaneously twice a week from the next week.
      Three and 6 weeks after AEF injection, mice were sacrificed and histologically
      examined. RESULTS: In the transient model, amyloid deposition was observed in the
      spleen, liver, and kidney as early as 2 weeks after treatment. MR16-1 completely
      prevented amyloid deposition. Although IL-6 production was not suppressed, SAA
      production was significantly suppressed. In the chronic model, substantial
      amyloid deposition was seen in multiple organs and tissues as well as the spleen,
      liver, and kidney. MR16-1 suppressed amyloid deposition in many organs, even when
      injected one week after AEF injection; it showed a tendency to decrease SAA and
      IL-6 levels were decreased. CONCLUSION: IL-6 is a key cytokine for the induction
      of AA-amyloidosis, and anti-IL-6R therapy appears promising for the treatment of
      AA-amyloidosis.

PMID- 15170928
TI  - Blood pressure destabilization and edema among 8538 users of celecoxib,
      rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and
      nonusers of NSAID receiving ordinary clinical care.
AB  - OBJECTIVE: To investigate the relationship between nonselective nonsteroidal
      antiinflammatory drugs (NS NSAID), rofecoxib, celecoxib, and risk of edema and
      blood pressure destabilization in patients with rheumatoid arthritis (RA) and
      osteoarthritis (OA) receiving ordinary clinic care. METHODS: Patients
      participating in a longterm outcome study reported drug use, as well as the
      presence of edema and blood pressure increases occurring during the previous 6
      months. To measure pure drug effect, analyses were restricted to 8538 patients
      who exclusively used a NS NSAID, rofecoxib, or celecoxib, and compared to
      nonusers of NS NSAID, rofecoxib, or celecoxib. We evaluated blood pressure
      destabilization using patient-reported increases in blood pressure and/or
      difficulty in controlling blood pressure. RESULTS: Compared with nonusers, after
      adjusting for age, sex, presence of RA, and history of heart disease and
      hypertension, patients using rofecoxib, but not celecoxib or NS NSAID, had an
      increased rate of edema (23.3% vs 18.0%), while the rates for celecoxib and NS
      NSAID were 17.5% and 18.2%, respectively. The adjusted risk of edema was
      significantly increased for rofecoxib compared to celecoxib (OR 1.33, 95% CI 1.08
      1.64). For blood pressure increases, among patients who did not report having
      hypertension, no significant increase was noted for NS NSAID and celecoxib
      compared with nonusers. However a significant increased risk of blood pressure
      increase was seen for rofecoxib (OR 2.08, 95% CI 1.41-3.06). Among patients who
      reported having hypertension, patients taking rofecoxib had a significant
      increased risk of blood pressure increase compared to nonusers (OR 1.55, 95% CI
      1.23-1.96), while the risks of blood pressure increase for users of celecoxib and
      NS NSAID were not significantly different than among nonusers. After controlling
      for age, sex, RA, and new starts on NSAID, the risk of blood pressure increase
      was significantly higher for users of rofecoxib than celecoxib (OR 1.21, 95% CI
      1.03-1.61) among patients with hypertension, and numerically higher for
      nonhypertensives (OR 1.42, 95% CI 0.96-2.22). The increased risk for hypertension
      and edema of rofecoxib compared to celecoxib users was further confirmed by
      analysis of specific reported side effects during 2 separate 6-month periods
      (July 1 to December 31, 1999, and January 1 to June 30, 2000). During these 2
      periods, rofecoxib-treated patients were 2.16 to 3.82 times more likely to report
      edema or blood pressure increase side effects compared to celecoxib-treated
      patients. CONCLUSION: Rofecoxib, but not celecoxib and NS NSAID, is associated
      with an increased risk of edema and blood pressure increase compared to nonusers
      of NSAID.

PMID- 15170929
TI  - Hypertension was the major risk factor leading to development of cardiovascular
      diseases among men with hyperuricemia.
AB  - OBJECTIVE: A 7-year followup study among men with hyperuricemia was conducted to
      study the longterm relationships between serum uric acid concentrations and
      cardiovascular diseases. Any interaction between uric acid levels and other risk
      factors (e.g., obesity, hypertension) on the development of cardiovascular
      diseases was also examined. METHODS: A total of 391 men with hyperuricemia aged
      30 and over screened from the community-based Kinmen study in 1991-92 (the
      baseline study) were followed in 1997-98, with a 75% followup rate. Demographic,
      clinical, and biochemical data were collected in both baseline and followup
      periods. RESULTS: After followup for 7 years, the significant risk factors of
      coronary heart disease were age, increase of uric acid level at followup,
      baseline systolic blood pressure, and increase of systolic blood pressure at
      followup. Factors independently associated with left ventricular hypertrophy
      included baseline systolic blood pressure and increase of systolic blood pressure
      at followup. Gouty syndrome, age, baseline fasting plasma glucose level, and
      increase of systolic blood pressure followup were significantly related to
      cardiac arrhythmia. After adjusting for baseline serum uric acid level, we found
      that hyperuricemic men with hypertension, especially overt hypertension stage 2
      and stage 3, would predict cardiovascular disease incidence synergistically with
      uric acid level. CONCLUSION: There is a positive and statistically significant
      relationship between gout and subsequent cardiac arrhythmia. Moreover,
      hypertension was the major risk factor leading to aggravation of development of
      atherosclerosis among hyperuricemic subjects. Gout and elevated uric acid level
      seemed not to be an independent risk factor for most cardiovascular diseases.
      Nevertheless, blood pressure level was predictive for cardiovascular disease
      incidence synergistically with serum uric acid level.

PMID- 15170930
TI  - Different progressions of hyperglycemia and diabetes among hyperuricemic men and
      women in the kinmen study.
AB  - OBJECTIVE: A 7-year followup study among hyperuricemic subjects was conducted to
      investigate the association between longterm hyperuricemia and subsequent
      hyperglycemia and diabetes mellitus. The possible sex difference was also
      investigated. METHODS: A total of 641 hyperuricemic subjects aged 30 years and
      over (391 men, 250 women) screened from the community-based Kinmen Study in 1991
      92 (the baseline study) were followed in 1997-98, with 75% followup rate.
      Demographic, clinical, and biochemical data were collected in both baseline and
      followup periods. RESULTS: After followup for 7 years, the distribution of plasma
      glucose concentrations changed moderately among male hyperuricemic subjects, but
      increased markedly among female subjects. The increase of uric acid levels during
      the followup period was correlated with subsequent diabetes only among
      hyperuricemic women. Moreover, a relatively higher incidence of diabetes was
      found in postmenopausal hyperuricemic women after 7-year followup. CONCLUSION:
      Although the direct role and causality played by uric acid cannot be confirmed by
      this study, the findings, as applicable to a Chinese nondiabetic population, show
      that specific progressions of plasma glucose concentrations were significantly
      different between male and female hyperuricemic subjects. Hyperuricemia and
      persistent increase in uric acid levels among postmenopausal women should alert
      physicians to the possibility of subsequent hyperglycemia and diabetes.

PMID- 15170932
TI  - Cartilage destruction in collagen induced arthritis assessed with a new
      biochemical marker for collagen type II C-telopeptide fragments.
AB  - OBJECTIVE: To assess the ability of a marker of collagen type II degradation (CTX
      II) to quantify cartilage turnover in vitro in cartilage explants and in vivo in
      rats with collagen induced arthritis (CIA). METHODS: Bovine articular cartilage
      explants were cultured in the presence of interleukin 1a, oncostatin M, and
      plasminogen to induce cartilage degradation. CTX-II, CTX-I (C-telopeptide
      fragment of collagen type I), glycosaminoglycan, and hydroxyproline contents in
      culture supernatants were measured. CIA was induced in 12-week-old female Lewis
      rats by immunization with bovine type II collagen. The incidence and severity of
      arthritis were monitored by measuring paw swelling, and urinary levels of CTX-II
      and CTX-I were determined. The knee joints of rats were histopathologically
      examined after sacrifice. Results. CTX-II but not CTX-I levels correlated well
      with collagen degradation in bovine articular cartilage in vitro quantified by
      hydroxyproline release. Urinary CTX-II levels as well as paw volume of CIA rats
      were significantly higher than normal rats on Days 21, 28, and 42 and were
      apparently correlated with cartilage destruction, assessed histopathologically.
      Urinary CTX-I level began to increase on Day 21, but only on Day 42 was it
      significantly different between CIA and normal rats. The elevation in CTX-I level
      appeared to occur later than that of CTX-II, in accord with the more delayed
      onset of bone erosion in the CIA model of rheumatoid arthritis. CONCLUSION:
      Urinary CTX-II may be a useful marker for evaluation of dynamics of cartilage
      destruction in CIA rats.

PMID- 15170931
TI  - The effect of a preoperative exercise and education program on functional
      recovery, health related quality of life, and health service utilization
      following primary total knee arthroplasty.
AB  - OBJECTIVE: To determine the effectiveness of a preoperative exercise/education
      program on functional recovery, health related quality of life (HRQOL), health
      service utilization, and costs following primary total knee arthroplasty (TKA).
      METHODS: One hundred thirty-one subjects were randomized to either the control (n
      = 66) or treatment (n = 65) group 6 weeks before TKA surgery. Patients in the
      treatment group underwent a 4-week exercise/education program before surgery. All
      subjects were assessed 6 weeks preoperatively (before the exercise/education
      intervention), immediately preoperatively (after the exercise/education
      intervention), and 3, 6 and 12 months after surgery utilizing the Western Ontario
      McMaster Osteoarthritis Index, the SF-36, and knee range of motion (ROM) and
      strength measures. Data on length of stay, numbers of community rehabilitation or
      homecare visits following discharge from the surgical hospital, and the costs
      associated with these services were also collected. RESULTS: Subjects were
      similar in demographic characteristics and all measurements at the baseline
      assessment. No differences were seen in knee measurements (ROM and strength),
      pain, function, or HRQOL between the 2 groups following the intervention program
      or at any postoperative measurement point. Patients in the treatment group used
      fewer postoperative rehabilitation services and stayed for a shorter time in
      hospital than the control group, but these differences did not attain statistical
      significance. CONCLUSION: The exercise/education intervention did not alter
      functional recovery or HRQOL following TKA. Health service utilization was less
      in the treatment group, but our study was underpowered to attain statistical
      significance for these measures.

PMID- 15170933
TI  - The comprehensive osteoarthritis test: a simple index for measurement of
      treatment effects in clinical trials.
AB  - OBJECTIVE: To assess the measurement properties of a simple index of symptom
      severity in osteoarthritis (OA) of the hips and knees. METHODS: Both the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the proposed
      new Comprehensive Osteoarthritis Test (COAT) instrument were completed weekly by
      125 subjects in the context of a randomized, 12-week, 3 parallel-arm clinical
      trial. The reliabilities of the various scales were assessed on a weekly basis by
      use of Cronbach's alpha coefficients. The validity of the COAT total scale was
      assessed by correlation with the WOMAC total scale on a weekly basis with
      correlation coefficients, and in terms of the correlations between subject-level
      intercepts and slopes over time. The relative responsiveness of the WOMAC and
      COAT total scales was assessed using a multilevel (longitudinal) multivariate
      (WOMAC, COAT) linear model. RESULTS: The WOMAC and COAT total scales were highly
      reliable (mean over weeks: WOMAC alpha = 0.98; COAT alpha = 0.97). The
      correlations between the WOMAC and COAT scales were very high (mean over weeks =
      0.92; subject-level intercepts = 0.91, slopes = 0.88). The COAT total scale was
      significantly more responsive than the WOMAC total scale in the active treatment
      (34.8% improvement vs 26.8%; p = 0.002). CONCLUSION: The COAT total scale is
      simple to administer, reliable, valid, and responsive to treatment effects.

PMID- 15170934
TI  - Important determinants of self-efficacy in patients with chronic musculoskeletal
      pain.
AB  - OBJECTIVE: To define the presenting characteristics of a population of patients
      with chronic musculoskeletal pain seen in a tertiary rheumatology clinic, and to
      investigate which factors are associated with self-efficacy in these patients.
      METHODS: Data were collected prospectively for 196 patients who attended the
      clinic for the first time between October 2000 and August 2002. The primary
      outcome measure was self-efficacy, measured using the Pain Self-Efficacy
      Questionnaire. Secondary outcome measures were pain intensity and disability due
      to pain. The data were analyzed using both univariate and multiple regression
      methods. RESULTS: These patients had typically undergone extensive investigations
      and tried various therapies but were left with persisting pain and poor self
      efficacy. Multiple regression analysis showed that after adjustment for other
      factors, the presence of depressive symptoms and employment status were
      associated with self-efficacy. Patients who reported depressive symptoms had mean
      self-efficacy scores 7.0 units lower (95% confidence interval, CI: 2.2-11.9) than
      those who did not. Being employed was associated with higher self-efficacy. The
      retired had scores 8.3 units lower than employed people (95% CI: 2.4-14.2),
      whereas housewives and the unemployed had scores approximately 14 units lower
      (95% CI: 8.0-20.9 and 7.5-19.0, respectively) than employed people. There was
      also some evidence that distribution of painful sites was associated with self
      efficacy. Patients with extensive pain had scores 4.1 units (95% CI: -0.4-8.6)
      lower than those with limited pain. CONCLUSION: Depressive symptoms, occupational
      status, and possibly distribution of pain are associated with the reported
      confidence of these patients with chronic pain in their ability to carry out
      everyday activities. Possible links to the idea of legitimacy of pain are
      discussed.

PMID- 15170935
TI  - Cyclic alternating pattern: a new marker of sleep alteration in patients with
      fibromyalgia?
AB  - OBJECTIVE: In the dynamic organization of sleep, cyclic alternating pattern (CAP)
      expresses a condition of instability of the level of vigilance that manifests the
      brain's fatigue in preserving and regulating the macrostructure of sleep. We
      evaluated the presence of CAP in patients with fibromyalgia (FM) compared to
      healthy controls. METHODS: Forty-five patients with FM (42 women) were studied
      and compared with 38 healthy subjects (36 women) matched for age, sex, and body
      mass index. Entry criteria were diagnosis of FM according to 1990 American
      College of Rheumatology criteria; willingness to participate in the study; and
      having no other diagnosis of autoimmune, neoplastic, or other possible causes of
      secondary diffuse musculoskeletal pain. Patients in the study underwent
      polysomnography recordings and a sleep questionnaire. Hypersomnolence was
      evaluated according to the Epworth Sleepiness Scale. RESULTS: FM patients had
      less sleep efficiency (sleep time/time in bed) than controls (79 +/- 10 vs 89 +/-
      6; p < 0.01), a higher proportion of stage 1 non-rapid eye movement (non-REM)
      sleep (20 +/- 5 vs 12 +/- 5; p < 0.001), and twice as many arousals per hour of
      sleep (9.7 +/- 3.3 vs 4.1 +/- 1.9; p < 0.01). The CAP rate (total CAP time/non
      REM sleep time) was significantly increased in FM patients compared to controls
      (68 +/- 6% vs 45 +/- 11%; p < 0.001). CAP rate seemed to correlate with the
      severity of clinical symptoms in FM patients (tender points index; p < 0.01) and
      with less efficiency of sleep (p < 0.01). CONCLUSION: The increase of CAP rate
      indicates a worse quality of sleep in patients with FM. These data are strongly
      correlated to the severity of symptoms.

PMID- 15170937
TI  - Association of single nucleotide polymorphisms within cytokine genes with
      juvenile idiopathic arthritis in the Czech population.
AB  - OBJECTIVE: To examine the possible association of juvenile idiopathic arthritis
      (JIA) with polymorphisms within cytokine genes in the Czech population. METHODS:
      In a case-control study, genotypes of 130 patients with JIA (63 male, 67 female;
      age at onset 7.6 +/- 4.4 yrs; 43 oligoarticular, 72 polyarticular, 15 systemic
      form) were compared to 102 healthy unrelated blood donors. Using the polymerase
      chain reaction technique with sequence-specific primers from the 13th IHWG
      workshop, we analyzed 19 single nucleotide polymorphisms within 12 different
      cytokine genes [interleukin (IL)-1a, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12,
      transforming growth factor (TGF)-beta, interferon (IFN)-g], and related molecules
      (IL-1R, IL-1RA, IL-4Ra). Genotype frequencies were compared using chi-square
      analysis, and the significance level was corrected for the number of independent
      tests. RESULTS: Significant positive association was found for the G allele of
      the IL-4 -1098 T/G polymorphism, which was carried by 10% of cases and 25% of
      controls [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.16-0.67, corrected
      p = 0.038). Also, a nonsignificant increase in the frequency of the IL-1beta
      +3962 C allele was detected in cases (96%) versus controls (84%) (OR 4.65, 95% CI
      1.64-13.2, corrected p = 0.091). We did not replicate previously found
      associations with the IL-1a, IL-6, IL-10, and IL-1RA polymorphisms. CONCLUSION:
      Our study showed association with JIA for the IL-4 -1098 T/G polymorphism. It
      also underlines the genetic contribution of IL-1 polymorphisms to the
      pathogenesis of JIA, as another polymorphism within the IL-1beta may influence
      the risk of the disease.

PMID- 15170936
TI  - Physician resources and postgraduate training in canadian academic rheumatology
      centers: a 5-year prospective study.
AB  - OBJECTIVE: To describe the trends in physician resources, changes in activity
      profiles, and the output of the postgraduate training programs in Canadian
      academic rheumatology centers from 1998-2002. METHODS: In 1998, the Canadian
      Council of Academic Rheumatologists (CCAR) established a prospective database to
      monitor physician resources, activity profiles, and recruitment within 15
      academic rheumatology units in Canada. Information was also collected on
      residents pursuing subspeciality training in rheumatology. RESULTS: Over the 5
      year period there was an increase in the number of rheumatologists from 157 to
      168. The majority of this increase (91%) was attributable to changes in full-time
      staff. The mean age of rheumatologists increased from 47.9 to 48.9 years over the
      same period and the ratio of male to female rheumatologists decreased
      incrementally from 2.5:1 to 1.9:1. The overall allocation of time for clinical
      care (54-53%), teaching (17-16%), research (21-23%), and administration (7%)
      remained stable over time. Unfilled staff positions varied between 18-25 per year
      and were spread between 9-12 centers. The number of trainees in adult and
      pediatric rheumatology fell incrementally from 38 to 22 over the first 4 years of
      the study, with an increase to 30 in 2002. The majority of trainees were located
      at 2 centers and the number of active training programs varied between 6 and 12
      per year. Funding for clinical fellowship training was provided by government (27
      51%), the Arthritis Society (21-33%), and alternative sources (23-40%).
      CONCLUSION: These results indicate that rheumatology physician resources within
      Canadian academic units are inadequate to fulfill responsibilities in the
      delivery of clinical service and academic programs. Enrollment in rheumatology
      training programs is falling and is insufficient to meet the present and future
      needs for patients with rheumatic diseases in Canada.

PMID- 15170939
TI  - Vasopressin cell antibodies and central diabetes insipidus in a patient with
      systemic lupus erythematosus and dermatomyositis.

PMID- 15170938
TI  - Antiagalactosyl IgG antibodies in juvenile idiopathic arthritis, juvenile onset
      Sjogren's syndrome, and healthy children.
AB  - OBJECTIVE: To determine the normal range of antiagalactosyl IgG antibodies in
      healthy children, and to investigate the utility of determination of
      antiagalactosyl IgG antibodies in patients with juvenile idiopathic arthritis
      (JIA) and juvenile onset Sjogren's syndrome (SS). METHODS: Serum concentrations
      of antiagalactosyl IgG antibodies were measured in 225 healthy children, 68
      patients with JIA (systemic arthritis in 21, polyarthritis in 29, oligoarthritis
      in 18), and 15 patients with juvenile onset SS, using a lectin-enzyme immunoassay
      employing prepared human agalactosyl IgG as antigen. A comparison was made
      between the prevalence and utility of antiagalactosyl IgG antibodies in patients
      and those of conventional rheumatoid factors (RF) determined by laser
      nephelometry. RESULTS: The average serum concentration of antiagalactosyl IgG
      antibodies for healthy controls was 2.41 +/- 0.93 arbitrary units (AU)/ml, and
      the cutoff value of the normal range was set at 4.3 AU/ml (mean + 2 SD). As a
      result, antiagalactosyl IgG antibodies were positive in 25 (37%) of 68 patients
      with JIA, and 14 (93%) of 15 patients with juvenile onset SS, in whom values were
      much higher than the frequencies of RF positivity. The serum concentrations of
      antiagalactosyl IgG antibodies in patients were closely correlated with those of
      RF. Thirteen patients with JIA and 6 patients with juvenile onset SS were
      positive for antiagalactosyl IgG antibodies despite being negative for RF. With
      regard to prognosis during followup periods of at least 5 years, JIA patients
      positive for antiagalactosyl IgG antibodies, even if negative for RF, were
      resistant to treatment. However, positivity for antiagalactosyl IgG antibodies
      had no relation to joint destruction. CONCLUSION: Our data suggest that
      antiagalactosyl IgG antibodies, compared with RF, show higher sensitivity to
      detect immunological disorders in JIA and juvenile onset SS.

PMID- 15170940
TI  - Identity loss due to chronic fingertip ischemia.

PMID- 15170941
TI  - Diagnosis and followup of Takayasu's arteritis by scintigraphy with radiolabelled
      interleukin 2.

PMID- 15170942
TI  - Effusive-constrictive pericarditis.

PMID- 15170943
TI  - Effusive-constrictive pericarditis.

PMID- 15170944
TI  - [Complications of renal transplantation. Contribution of radionuclide
      evaluation].

PMID- 15170945
TI  - Body growth and lymphocyte DNA polymerase activity in patients with
      hypopituitarism.

PMID- 15170946
TI  - [Hormonal responses in patients with nonfunctioning pituitary tumors].

PMID- 15170947
TI  - Induction of sister chromatid exchanges in rabbit lymphocytes by
      medroxyprogesterone.

PMID- 15170948
TI  - Induction of sister chromatid exchanges in mouse kidney fibroblasts by
      medroxyprogesterone acetate.

PMID- 15170949
TI  - [Respiratory activity of cardiac and hepatic mitochondria in rat in chronic
      hypobaric hypoxia ].

PMID- 15170950
TI  - Detection of intermediate density lipoproteins in the plasma of diabetic
      patients.

PMID- 15170951
TI  - [Pathology of persistent infection of Calomys musculinus with an attenuated
      strain Junin virus].

PMID- 15170952
TI  - [Decrease of cytochromes and mitochondrial protein biosynthesis in skeletal
      muscle of diabetic rats].

PMID- 15170953
TI  - [Effect of intracerebral inoculation of Junin virus in guinea pigs].

PMID- 15170954
TI  - [Chondroma simulating bronchial asthma].

PMID- 15170955
TI  - [Disturbance of blood coagulation and alcoholic liver disease: clinical
      conference].

PMID- 15170956
TI  - [Electrophysiological studies. Its present clinical use].

PMID- 15170957
TI  - [Incidence and diagnosis of pulmonary thromboembolism].

PMID- 15170958
TI  - [Interferon: from the alchemy to molecular biology].

PMID- 15170959
TI  - [Cell Membrane and malignity].

PMID- 15170960
TI  - [Effect of treatment with immune sera in rats infected with Junin virus].

PMID- 15170961
TI  - [Pituitary microadenoma and polytomography].

PMID- 15170962
TI  - A longitudinal study of Medicaid payment, private-pay price and nursing home
      quality.
AB  - Quality of care problems have persisted for decades within U.S. nursing homes. A
      potential state-level policy towards addressing this concern is the level of
      Medicaid payment. However, a number of studies have found that an increase in
      Medicaid payment is associated with lower quality in the presence of certificate
      of-need (CON) laws and bed construction moratorium regulations, which serve as
      barriers to entry within the nursing home industry. Instead of relying on
      potentially confounded cross-sectional comparisons, this study presents novel,
      panel-based evidence that incorporates aggregate private-pay price data. These
      estimates almost uniformly indicate that an increase in the Medicaid payment rate
      raises nursing home quality. When compared to the earlier literature, these new
      findings are attributed to changes over time in the market for nursing home care
      related to the growth in nursing home substitutes.

PMID- 15170963
TI  - Estimating the compensating differential for employer-provided health insurance.
AB  - The theory of wage differentials argues that workers must pay for employer
      provided group health insurance coverage through lower wages or reductions in
      other fringe benefits. This paper uses data from the 1988-90 Consumer Expenditure
      Survey (CEX) to estimate the wage-health insurance trade-off for male workers
      between the ages of 25 and 55. A fixed-effects model, which takes advantage of
      the rotating panel design of the CEX, is used to control for unobservable worker
      characteristics that are positively related with all forms of compensation,
      including wage earnings and health insurance coverage. I find a compensating
      differential for health insurance equal to roughly 10 to 11 percent of wages.
      Some caution is advised here due to the fact that I was unable to control for
      other fringe benefits, the most important being paid vacation and sick leave.

PMID- 15170964
TI  - Do routine eye exams improve vision?
AB  - We use a longitudinal national sample of Medicare claims linked to the National
      Long-Term Care Survey (NLTCS) to assess the productivity of routine eye
      examinations. Although such exams are widely recommended by professional
      organizations for certain populations, there is limited empirical evidence on the
      productivity of such care. We measure two outcomes, the ability to continue
      reading, and no onset of blindness or low vision, accounting for potential
      endogeneity of frequency of eye exams. Using instrumental variables, we find a
      statistically significant and beneficial effect of routine eye exams for both
      outcomes. Marginal effects for reading ability are large, but decline in the
      number of years with eye exams. Effects for blindness/low vision are smaller for
      the general elderly population, but larger for persons with diabetes.
      Instrumental variables provide a useful approach for assessing the productivity
      of particular interventions, particularly in situations in which randomized
      controlled trials are expensive or perhaps unethical and difficult to conduct
      over a lengthy time period.

PMID- 15170965
TI  - Competition or coordination in hospital markets with unionised labour.
AB  - This paper study labour market responses to hospital mergers. The market consists
      of two hospitals providing horizontally and vertically differentiated services.
      Hospitals compete either in price and quality or just in quality (non-price
      competition). To provide medical care, hospitals employ health care workers
      (e.g., physicians, nurses). The workers collectively bargain wages either at a
      central level, firm level or plant level. Anticipating wage responses, hospitals
      decide whether or not to merge. The main finding is that the bargaining
      structure, the nature of competition and the patient copayment rate have a
      crucial impact on the profitability of hospital mergers.

PMID- 15170966
TI  - [Current imaging methods in Graves' ophthalmopathy].
AB  - Imaging of the extraocular muscles and orbital soft tissues in Graves'
      orbitopathy provides valuable information for both diagnosis and treatment
      decisions. However, assessment of the activity of the autoimmune process is often
      difficult. Currently available scoring systems for activity estimation are based
      merely on complaints and physical and ophthalmological examination. A reliable
      laboratory parameter correlating with disease activity is also missing.
      Sonography and magnetic resonance studies have pointed out, that thickening
      and/or edema of the extraocular muscles are often present before the onset of
      clinical symptoms and complaints. MRI and scintigraphy may provide important
      information upon the activity of the orbital process. Since the disease
      progrediates in the absence of therapy, it is essential to launch a properly
      timed immunosuppressive treatment in a selected group of patients. Based on their
      long-term experience in the Medical and Health Science Center of the University
      of Debrecen, Hungary, the authors review the currently available imaging methods
      in the diagnosis and follow up of endocrine orbitopathy, emphasizing their
      advantages and drawbacks.

PMID- 15170967
TI  - [Results of imatinib therapy in late-stage chronic myeloid leukemia after
      treatment with interferon-alpha].
AB  - BACKGROUND: Chronic myelogenous leukemia is characterised by the presence of
      Philadelphia translocation and consecutive expression of bcr-abl oncogene with
      enhanced tyrosine kinase activity, which is known to be the essential
      pathogenetic event in the disease. Imatinib (Glivec, formerly STI571) is a highly
      selective inhibitor of the bcr-abl tyrosine kinase which has shown a promising
      therapeutic activity in chronic myeloid leukemia as the first molecularly
      targeted antinoplastic treatment. METHODS: Between January 2001 and October 2001,
      54 patients with chronic phase CML, resistant or intolerant to interferon-alpha
      were enrolled into the Novartis Expanded Access Study (Protocol 0113). Patients
      characteristics were as follows: male/female: 32/22, median age: 49 years (range:
      22-75), median duration of disease: 44 months (range: 3-152). All patients
      received 400 mg imatinib orally. RESULTS: Complete hematologic response was
      obtained in 53 patients (96%) within 4 weeks. Major cytogenetic response (< 35%
      Ph+ metaphasis) was achieved after 6 months in 62.9%, and after 12 months in
      64.8% of patients. Three patients progressed during the treatment (loss of
      complete hematologic response or cytogenetic response 1, blastic phase 2). The
      treatment was well tolerated, with mild side effects. Main non-hematologic side
      effects were weight gain and fluid retention. CONCLUSIONS: The results confirm
      that imatinib is highly active in inducing complete hematologic response and
      major cytogenetic response in most patients who failed interferon-alpha.
      Treatment was well tolerated with rare and mild adverse events and impressive
      improvement of quality of life.

PMID- 15170969
TI  - [Medical problems associated with the national reference pricing system in
      Hungary].
AB  - The author analyses the medical problems associated with the proposed reference
      pricing system prepared for the 2004 pharmaceutical price and reimbursement
      negotiations by the Hungarian National Health Insurance Fund (HNIF). In case of
      drugs containing identical active ingredients the author does not consider it
      acceptable that from the criteria of reference grouping bioequivalence was
      omitted, since bioequivalence is the basic clinical pharmacologic principle
      underlying the safe utilization of generic drugs. The proposal introduces in
      Hungary the therapeutic reference pricing for drugs belonging to the same ATC 5
      level group, having different chemical structures but identical mechanisms of
      action. The products are listed according to their defined daily dose (DDD) and
      the arithmetic mean of the cheapest products giving together 50% market share is
      calculated. Each ATC 5 group has a given per cent reimbursement level and the
      fixed amount paid by the HNIF for all drugs in the group is defined as the given
      percentage of the mean price. This sum is reimbursed irrespective whether the
      products are patent protected or not, furthermore those drugs whose price is
      three times higher than the fixed mean price are excluded from the reimbursement
      system. As a result the patients' co-payment for the more expensive drugs will be
      significantly increased in the future. The basis of the therapeutic reference
      price is the assumption that the outcome of the treatment will be the same using
      drugs with the same mechanism of action. However, this assumption lacks valid
      scientific proof. According to the author, the proposed budget centric reference
      pricing system, which does not take into account the differing clinical
      pharmacologic profiles of the drugs, will significantly inhibit the use of new,
      innovative drugs, the establishment and continuous improvement of truly cost
      effective patient care. Several alternative approaches are proposed for
      controlling drug budget. Finally the author recommends that a Committee should be
      established to develop a comprehensive proposal for the reorganization of the
      pricing and reimbursement system of the drugs available for general and/or
      hospital use, and for the follow-up of the health care effects of these measures.

PMID- 15170968
TI  - [Mutational analysis of the MECP2 gene by direct sequencing in Hungarian patients
      with Rett syndrome].
AB  - INTRODUCTION: Rett syndrome is an X-linked neurodevelopmental disorder
      characterized by loss of acquired skills and stereotypical hand movements.
      Mutations in the gene encoding methyl-CpG-binding protein 2 have been identified
      as cause of Rett syndrome in 1999. AIM: The authors initialized mutation
      screening of this gene in Hungarian patients identified on the base of clinical
      manifestation in various institutes. So far 25 patients were examined who were
      supposed to have Rett syndrome. METHOD: Total genomic DNA was extracted from
      peripheral blood with routine desalting method for mutation analysis. The three
      coding regions of the gene were amplified with primer pairs described. The PCR
      products were analysed by direct sequencing. RESULTS: Mutations in methyl-CpG
      binding protein 2 gene were found in 17/25 cases (68%). This rate of mutation
      among Rett patients corresponds well with the findings of other studies. Two
      novel mutations were found. In the first patient whose history was characterized
      by a slower than normal progression, a G insertion at the base position 276 of
      exon 3 was detected, while in the second child a double deletion (191, and 9
      bases, resp.) in exon 4 was identified.

PMID- 15170970
TI  - [Possibilities of postnatal diagnosis in congenital cytomegalovirus infection].
AB  - The authors review two cases of suspected congenital cytomegalovirus (CMV)
      infections in which modern laboratory approaches were applied to establish the
      diagnosis postnatally. In the first case, intrauterine infection was suggested by
      ventriculomegaly, detected by means of a head ultrasonographic scan. The
      postnatal cranial ultrasonography and computed tomographic scans revealed
      intracerebral calcifications. CMV was detected in the blood and urine of the
      newborn. The postnatal serological tests proved that the mother had experienced a
      primary CMV infection during gestation. Abnormal neurological signs developed in
      the infant by the age of 9 months. In the second case, the mother had had an
      active CMV infection at 29 weeks of gestation involving a twin pregnancy. The CMV
      specific serological tests demonstrated that this was a recurrent infection. The
      twins were born without signs or clinical symptoms and CMV was not detected in
      their urine samples. At 5 months of age, one of the twins excreted CMV in his
      urine, which must have been a consequence of a postnatal infection. The general
      screening of young women by CMV serology at the beginning of gestation is
      recommended. This would establish a CMV serostatus and provide an opportunity for
      the gynecologist to provide advice concerning the avoidance of infection,
      especially in cases where the patient is seronegative and therefore at risk of
      primary CMV infection.

PMID- 15170972
TI  - [Current status and measures for lung injuries in cancer treatment].
AB  - The current status and measures for anticancer drug-induced lung injury and
      radiation pneumonia in cancer treatment were reviewed. Interstitial pneumonia
      induced by anticancer drugs is pathologically classified into the following:
      chronic interstitial pneumonia (CIP) or nonspecific interstitial pneumonia
      (NSIP), eosinophlic pneumonia (EP), bronchiolitis obliterans-organizing pneumonia
      (BOOP), diffuse alveolar damage (DAD), and hypersensitivity pneumonia (HP). In
      these pulmonary reactions to anticancer drugs, interstitial pneumonia manifested
      by DAD, which shows the acute or chronic clinical course, presents high mortality
      rates. Therefore, special care should be taken when DAD develops. Radiation
      pneumonia has two clinical phases, an acute phase of injury termed radiation
      pneumonitis, and a chronic phase of injuring termed lung fibrosis. It is usually
      confined to the irradiated area. On the other hand, sporadic radiation
      pneumonitis occurring outside the irradiated area has been reported besides
      classic radiation pneumonitis. Pathologically, it shows lymphocytic alveolitis or
      BOOP. Although radiation pneumonia has a good prognosis, mortality is rarely
      observed when lesion spreads outside the irradiated area.

PMID- 15170971
TI  - [Therapy in Alzheimer disease].

PMID- 15170973
TI  - [Current status on laparoscopic surgery for colorectal cancer].
AB  - The current status of laparoscopic surgery and its indications for colorectal
      cancer are described. According to multi-institutional registry by the Japanese
      Society of Endoscopic Surgeons, the number of laparoscopic surgeries for advanced
      colorectal cancer has been increasing during the last couple years. The short-
      and long-term results of laparoscopic surgery for pT1 or pT2 colon cancer are
      favourable, and laparoscopic surgery could be a standard procedure for such
      cases. However, the indications for pT3/T4 cancer remain controversial due to
      limited length of follow-up. A multi-centre randomised controlled trial (RCT)
      comparing open with laparoscopic surgery for advanced (T3/T4) cancer is to start
      in autumn this year. Laparoscopic surgery for such cases should be confined to
      trial cases. Laparoscopic surgery for rectal cancer is feasible; however, it is
      associated with higher anastomotic leak rates. Issues on education and medical
      costs need to be resolved.

PMID- 15170974
TI  - [Surgical treatment for colorectal liver metastases--results of multi-institute
      study for effects of radical hepatectomy].
AB  - Four hundred and ten patients with colorectal liver metastases underwent radical
      liver resection from 1992 to 1996 at 15 institutes were reviewed retrospectively.
      Survival rates were calculated for more than 5 years after hepatic resection and
      timing of surgery and recurrences, maximum diameter and number of liver
      metastases, and intrahepatic recurrence were examined. There was no significant
      difference in survival rates for the type of liver resection (partial or
      anatomical) or preoperative serum CEA levels. As for the number of metastases,
      the 5-year survival rate was lower for patients with over 4 metastases than those
      with 1, 2, and 3 metastases (p < 0.034). A significant difference in survival
      rates was recognized for size of liver metastases (p = 0.0309) as follows: 54.6%
      5-year survival rate for smaller than 4 cm and 43.8% for over 4 cm. Overall 5
      year survival rate for the 410 patients was 50.1% after radical hepatectomy. Of
      the 410 patients, the 153 (37.3%) patients with intrahepatic recurrence had a 5
      year survival rate of 27.3%. The 5-year survival rates for patients with a
      metastasis smaller than 4 cm, considered to reduce the influence in the
      difference between surgical procedure or indication for surgery, were verified to
      be from 88.2% to 11.9% in each institute. This suggests that there could be a
      difference in diagnostic accuracy, surgical indication or timing of surgery for
      synchronous liver metastases in each institute.

PMID- 15170975
TI  - [Microwave coagulation therapy for liver metastases from colorectal cancer].
AB  - Hepatic resection has gained acceptance as the most effective therapy for liver
      metastases from colorectal cancer. Microwave coagulation therapy (MCT) and
      radiofrequency ablation as well as resection are also reported as effective
      therapies. We analyzed the prognosis of 52 patients with liver metastases from
      colorectal cancer treated with MCT as the first radical therapy. A total of 4
      percutaneous MCT's (3 cases with interruption of hepatic blood flow), 23 MCT's
      with laparotomy, and 25 with hepatic resection + MCT with laparotomy were
      performed. Thirty-three MCT's performed as a second therapy for recurrence in the
      liver were also analyzed. Clinical risk scoring as reported by Fong, et al was
      used in our cases. The indication for percutaneous MCT with interruption of
      hepatic blood flow is solitary tumor less than 20 mm in diameter. The 5-year
      survival rate for the 4 percutaneous MCT's, 23 MCT's with laparotomy, and 25
      hepatic resection + MCT's with laparotomy and 68 hepatic resections were 20, 24
      and 24%, respectively. No significant difference was found among them. The 5-year
      survival rate for the 17 MCT's and 12 hepatic resections with recurrence in the
      liver were 20% and 24%, respectively. There was no significant difference found
      between them. The 5-year survival rate for the 28 CRS3 was 17%, almost equal to
      the rate, 20%, reported by Fong, et al for hepatic resections only. MCT is
      effective therapy for liver metastases from colorectal cancer, recurrence in the
      liver, and hepatic resections.

PMID- 15170976
TI  - [Hepatic arterial infusion chemotherapy for colorectal liver metastases].
AB  - Hepatic metastases are a frequent complication of colorectal cancer. Resection of
      liver metastases can result in long-term survival. However, the majority of
      patients have unresectable disease. Alternative methods in Japan for treating
      these patients are hepatic arterial infusion (HAI) chemotherapy with
      administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of
      HAI chemotherapy in terms of colorectal hepatic metastases today. HAI
      chemotherapy produced higher response rates compared with systemic chemotherapy,
      but did not demonstrate elongation of survival time in many trials. Important
      problems remaining to be solved are the technical aspects of percutaneous
      implantation of intraarterial catheters connected to a subcutaneous infusion
      reservoir and studies of combined therapy with systemic chemotherapy.
      Furthermore, in order to finally determine the position of HAI for colorectal
      liver metastases, it is necessary to conduct a comparative study versus systemic
      chemotherapy, using the survival time as the primary end point.

PMID- 15170977
TI  - [Chemotherapy].
AB  - Cancer chemotherapy in the treatment of colorectal cancer has been evolving so
      extensively than ever. 5-fluorouracil (5-FU) has been a pivotal and a single
      active agent in the treatment of colorectal cancer. Reproducing and consistent
      better response rate has been shown since the introduction of the concept of
      biochemical modulation of 5-FU by leucovorin, a reduced folate, to the clinic and
      a combination chemotherapy of 5-FU and leucovorin (FL) has enable us to obtain a
      response rate around 20-30% and a median survival time ranging from 10 to 12
      months. IFL regimen combing CPT-11 with FL showed a better MST ranging from 14 to
      15 months, but now serious toxicity precludes general use outside of clinical
      trials. In the Europe, de Gramont regimen, an unique dose and schedule of 5-FU
      using a combination of continuous intravenous infusion of 5-FU with leucovorin
      over two days and bolus infusion of 5-FU twice over the same period, has been
      developed and shown improved antitumor activity and toxic profiles. FOLFOX 4, a
      combination chemotherapy of de Gramont regimen and oxaliplatin which is a third
      generation of cisplatin and a uniqe toxic profile with neuropathy, has
      demonstrated improved MST over a year and acceptable toxic profiles. Now FOLFOX 4
      is considered to be a standard chemotherapy for the patients with advanced
      colorectal cancer, since a large phase III randomized study has shown that FOLFOX
      4 was the most active and less toxic treatment regimen among active regimens such
      as IFL and IROX (CPT-11 and oxaliplatin). More recently, a combination of IFL and
      bevacizumab which is one of the molecular target agents and a antibody agent
      against vascular endothelial growth factor (VEGF), has demonstrated better MST
      reaching 20 months. Future large scale trials will attempt to develop more active
      regimen incorporating so-called molecular target agents.

PMID- 15170978
TI  - [Clinical study for determination of the dosage formula for intra-arterial
      infusion chemotherapy with nedaplatin].
AB  - Area under the curve (AUC) is a very important parameter for determination of
      optimal dosage of antineoplastic agents in order to avoid side effects and
      achieve high effectiveness. Also, even if a certain dosage is administered,
      measured AUC is different in each individual. Therefore, it is important to
      determine the formula of the dosage of antineoplastic agents. We treated oral
      cancer using an intra-arterial infusion chemotherapy with nedaplatin (CDGP).
      Eighteen patients were treated with CDGP at the Department of Oral and
      Maxillofacial Surgery, Faculty of Medicine, Kagawa Medical University, from
      October 1998 to June 2002. The correlation among expected AUC, dosage, CDGP
      clearance and 24 hr creatinine clearance in all chemotherapy was monitored and
      examined. The obtained formula in the dosage of intra-arterial infusion
      chemotherapy with Nedaplatin was as follows. dosage = AUC x (0.027 x CCr + 7.17).

PMID- 15170979
TI  - [Clinical usefulness of UFT and cyclophosphamide as salvage chemotherapy for
      patients with metastatic breast cancer].
AB  - A combination of UFT and cyclophosphamide (CPA) was orally administered to 12
      women with previously-treated advanced or recurrent breast cancer. The daily dose
      of UFT was 400 to 600 mg for tegafur and 100 mg for CPA. Treatment was given
      orally for 2 weeks followed by 1 week of no treatment, or for 5 days followed by
      2 days of no treatment. The response to treatment was CR in 2 patients, PR in 2,
      and long NC in 2. The response rate was 33.3%, and the clinical benefit 50%.
      Adverse reactions comprised grade 3 diarrhea requiring admission in 1 patient,
      over grade 1 leukopenia in 5 patients, and thrombocytopenia in 2 patients. These
      reactions could be controlled. The combination of UFT and CPA can be given on an
      outpatient basis and is considered a useful regimen for the management of
      previously-treated advanced or recurrent breast cancer.

PMID- 15170980
TI  - [Retrospective analysis on efficacy and toxicity of paclitaxel-containing
      treatments in patients with advanced or recurrent breast cancer].
AB  - Our department recently began using paclitaxel in treating patients with breast
      cancer. Retrospective analysis was conducted to clarify its clinical usefulness.
      Forty-one patients with metastatic breast cancer were treated with paclitaxel
      between November 2000 and September 2002. Hospital records of the patients,
      except for one unsensored patient, were retrospectively reviewed. Characteristics
      of the patients were as follows: age, 36-81 Y (median, 56); 8 stage IV and 32
      recurrent diseases; most frequent dominant site of metastasis was the liver (22
      patients, 55%); number with previous chemotherapy was 0-5 (median, 2);
      anthracycline-based treatment and docetaxel treatment were previously performed
      in 21 (53%) and 15 (38%) patients, respectively; weekly dose of paclitaxel was 30
      150 mg/body (median, 100); and total dose administered was 600-6, 480+ mg/body
      (median, 1,820). Objective response and clinical benefit rates were 35% and 80%,
      respectively. Median duration of response, time-to-progression and overall
      survival were 27+, 33+ and 41.5 weeks, respectively. Common adverse events were
      sensory neuropathy (45%) and nausea/vomiting (37.5%). Most were graded as 1 or 2.
      Various agents, such as hormonal agents and trastuzumab, were administered with
      paclitaxel in 26 patients (65%). No significant difference was observed in
      efficacy or toxicity among patients treated with paclitaxel alone or paclitaxel
      plus other agents. Paclitaxel seems to be a feasible, safe and active agent for
      patients with metastatic breast cancer.

PMID- 15170981
TI  - [An institution-randomized trial of 5-fluorouracil and l-leucovorin therapy given
      monthly versus every two months to patients with advanced colorectal carcinoma].
AB  - The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil
      (5-FU) and l-leucovorin (l-LV) given at the same dose intensity and administered
      monthly (given weekly for 3 weeks followed by a week of rest; arm A) or every 2
      months (given weekly for 6 weeks followed by 2 weeks rest; arm B) to patients
      with advanced colorectal carcinoma. The dose of 5-FU was 500 mg/body or 750
      mg/body, with an average dose of 432.8 mg/m2. A total of 7 institutions
      participated in this multi-center study and were randomly divided into 2 groups
      of arms A and B. Thirty-three patients were entered into arm A and 21 into B. The
      overall response rate was significantly (p = 0.007) greater in arm B (23.5%) than
      in arm A (0%). The most frequently observed toxicity was diarrhea, which was
      observed in 6.5% of arm A and in 33.3% of arm B, marking a significant difference
      (p = 0.034). These data suggest that a monthly 5-FU/l-LV regimen might be less
      toxic than a 2-months regimen and less effective at the dose given as above.
      Further study is needed to evaluate the efficacy of a monthly regimen.

PMID- 15170982
TI  - [Renal transplantation surgery is closely linked with treatment for bilateral
      synchronous renal cell carcinomas or renal tumors in solitary kidney].
AB  - We describe 4 cases of bilateral synchronous renal cell carcinoma and 3 of renal
      tumor in solitary kidney. One of the 3 patients with renal tumor in solitary
      kidney underwent partial nephrectomy. The remaining 2 patients, who had renal
      tumors greater than 7 cm located in the central region, underwent extracorporeal
      surgery. Development of acute renal failure and renal bleeding after ex vivo
      surgery occurred in 1 female patient, who required autograftectomy and temporary
      dialysis but subsequently underwent a re-operative procedure for renal
      transplantation with a kidney donated by her 82-year-old mother. Two of the 4
      patients underwent partial nephrectomy, 1 with multiple bone and lung metastases
      had all carcinoma foci extracted at the second stage and was administered UFT and
      IFN alpha, and the remaining 2 patients, who both had hereditary renal cell
      carcinoma with multiple tumors in both kidneys, received living-donor related
      renal transplantation soon after bilateral nephrectomy. In the period of follow
      up, ranging from 2 to 14 years, all the patients are well with no relapse and
      have good renal function. These results indicate kidney transplant procedures may
      have been linked with the options of bilateral synchronous renal cell carcinoma
      and renal tumor in solitary kidney.

PMID- 15170983
TI  - [Four cases of hypopharyngeal cancer treated with docetaxel, cisplatin, and 5-FU
      followed by radiotherapy and/or neck dissection].
AB  - We treated 4 patients with hypopharyngeal cancer, each of whom had a complete
      response after 2 cycles of chemotherapy with docetaxel, cisplatin, and 5-FU
      followed by radiation and/or neck dissection. Twenty-one months to 2 years after
      this therapy, 3 patients had no recurrence and no metastasis with their laryngeal
      framework and function preserved. Chemotherapy including docetaxel, cisplatin,
      and 5-FU is a useful treatment for early head and neck cancer.

PMID- 15170984
TI  - [A pilot study of trastuzumab and vinorelbine-combined therapy for metastatic
      breast cancer].
AB  - We performed combined therapy with trastuzumab-vinorelbine for 6 HER2 positive
      metastatic breast cancer patients from which informed consent was obtained. As
      the initial dosage, we administered 4 mg/kg of trastuzumab, followed by a dosage
      of 2 mg/kg every week thereafter. At the same time, 25 mg/m2 of vinorelbine was
      administered for 2 weeks, followed by a week of rest. Total administration
      frequency of trastuzumab was 13-34 times (median: 27 times) and vinorelbine was 8
      22 times (median: 17 times). A partial response was seen in 4 patients and no
      change in 2, for a response rate of 66%. A fixed period effect was recognized in
      each case, and the TTP was 112-274 days (median: 205 days). The side effects
      recognized were leukopenia of grade 3 in 1 patient, but she recovered during a
      withdrawal period. After that, continuous administration was possible.
      Trastuzumab-vinorelbine combined therapy expanded treatment alternatives for HER2
      positive metastatic breast cancer patients and might prolong life.

PMID- 15170986
TI  - [A case of large-cell lung cancer with marked leukocytosis successfully treated
      with chemoradiotherapy].
AB  - A 45-year-old woman was transferred to our hospital for further examination of a
      persistent fever, marked leukocytosis and abnormal shadow on chest CT scan. At
      the time of admission, her leukocyte count was 48,800/microliter and her chest CT
      scan showed a solitary nodule in the right upper lobe with hilar and mediastinal
      lymphadenopathy. A US-guided biopsy revealed a large-cell carcinoma. She was
      given radiation (total 60 Gy) and 4 courses of chemotherapy with paclitaxel (150
      mg/m2) in combination with carboplatin (AUC = 5). The primary tumor and swollen
      lymph nodes disappeared and leukocyte count normalized. Although 3 years have
      passed, no recurrence has been observed.

PMID- 15170985
TI  - [Effective weekly paclitaxel therapy for massive metastatic breast cancer].
AB  - A 36-year-old woman with a 12-year disease free interval after radical mastectomy
      for breast cancer presented with dyspnea and lumbago. Chest CT and bone
      scintigraphy revealed numerous bilateral pulmonary metastatic nodules, pleural
      effusion and multiple bone metastases. We treated her with weekly paclitaxel
      therapy at a dose of 80 mg/m2, which was continued for 3 weeks followed by 1 week
      rest, and bisphosphonate biweekly. Lung lesions markedly decreased in number and
      size after 6 infusions, and disappeared after 12. Bone scintigraphy showed
      partial response. Lung effect (CR) and bone effect (PR) have been maintained
      after 30 infusions on an outpatient basis. The patient tolerated the treatment
      well without adverse effect, except for moderate alopecia.

PMID- 15170987
TI  - [A case of metastatic esophageal cancer responding remarkably to combination
      chemotherapy of TS-1 and cisplatin].
AB  - A 51-year-old male patient with esophageal cancer and cervical, thoracic and
      celiac artery lymph node metastases was treated by combination chemotherapy of TS
      1 and cisplatin. TS-1 (80 mg/m2/day) was administered for 14 days followed by 14
      days rest as 1 course. Cisplatin (70 mg/m2/day) was administered in 24-hour
      continuous intravenous infusion at day 8 after the start of TS-1. Before
      treatment, the tumor marker, CEA showed 27,060 ng/ml. After 5 courses of
      chemotherapy, endoscopy revealed that the primary tumor had disappeared and no
      cancer cells were detected by endoscopic biopsy. Chest and abdominal CT scan also
      showed almost total disappearance of the lymph nodes metastases. CEA decreased to
      710 ng/ml. No high-grade toxicities (WHO grade 3 or 4) were seen during the
      chemotherapy. He is now very well. This TS-1/cisplatin chemotherapy regimen might
      be a useful treatment for metastatic esophageal cancer.

PMID- 15170988
TI  - [Efficacy of weekly administration of paclitaxel for advanced or recurrent
      gastric cancer with peritoneal dissemination].
AB  - We report 3 gastric cancer patients with peritoneal dissemination who failed to
      take TS-1 due to adverse effects and who were successfully treated with weekly
      paclitaxel administered intravenously. The patients were 2 men and 1 woman from
      73 to 82 years in age. The histological types of gastric cancer were
      undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80
      mg/m2) after short premedication was continued for 3 weeks followed by 1 week
      rest. Clinical symptoms, including ascites and intestinal obstruction, improved
      only after administration of 1 cycle in all patients. Except for 1 event with
      grade 3 neutropenia, no major adverse reactions were observed. Weekly
      administration of paclitaxel may be a promising chemotherapy for controlling
      peritoneal metastasis and improving the quality of life of patients with advanced
      or recurrent gastric cancer.

PMID- 15170989
TI  - [Two cases of recurrent gastric cancer treated by combined chemotherapy of TS-1
      and low-dose cis-platinum].
AB  - We report 2 patients with recurrent gastric cancer treated by combined
      chemotherapy of TS-1 and low-dose cis-platinum (TS-1/LCDDP). Who both obtained
      long-term survival while maintaining good QOL. Case 1: A 60-year-old man
      underwent total gastrectomy for gastric cancer (pT3, pN2, Stage III B). Three
      months after surgery, multiple liver metastases were identified, for which TS
      1/LCDDP therapy (TS-1 100 mg/body/day, CDDP 10 mg/body/week; 1 course for 4
      weeks) was started without hospitalization. After CR was obtained after 4
      courses, an additional 4 courses were carried out. At present, 1 year and 11
      months have passed since the initial treatment, and CR has been maintained.
      Regarding adverse events, only grade-1 pigmentation was observed. Case 2: A 65
      year-old man with gastric cancer (pT3, pN1, Stage III A) underwent distal
      gastrectomy. One year after surgery, CT showed both multiple liver and pulmonary
      metastases. Twelve courses of TS-1/LCDDP therapy have been carried out for 2
      years and 4 months. Therapeutic effect was NC, but the patient was able to
      tolerate the treatments as an outpatient without any subjective symptoms.
      Leukopenia (grade 2), pigmentation, stomatitis and nausea (grade 1) were
      observed. Both patients received TS-1/LCDDP therapy as outpatients with good QOL
      and performance status (0). Recently, chemotherapy for recurrent cancer has been
      focusing on long-term survival and maintenance of QOL, instead of tumor
      shrinkage. These results suggest that TS-1/LCDDP treatment is useful as a first
      line chemotherapy for patients with recurrent gastric cancer.

PMID- 15170990
TI  - [Two cases of recurrent gastric cancer at anastomosis medicated by TS-1].
AB  - Two cases of recurrent gastric cancer are described. Recurrence at anastomosis
      was detected following total gastrectomy in both patients. They declined surgery
      but wanted medical treatment. Therefore, 100 mg/kg of TS-1 was administered with
      informed consent. Symptoms related to stenosis were relieved after the first
      course, and complete responses were confirmed by endoscopic and pathological
      studies after completion of 4 courses in both patients. Palliative surgery
      remains a major option of treatments for patients with recurrence at anastomosis
      after total gastrectomy. TS-1, however, should be considered a treatment for such
      cases with satisfactory QOL, especially for outpatients who do not want surgery.

PMID- 15170991
TI  - [Home chemotherapy by concomitant UFT + Leucovorin (po.) in postoperative
      colorectal cancer patients assessed with Dukes D and curability C colorectal
      cancer].
AB  - Concomitant treatment with 5-fluorouracil (5-FU) and Leucovorin (LV) is
      positioned as the standard chemotherapy against colorectal cancer. We noted the
      action of LV to enhance the effect of biochemical modulation by 5-FU, and made an
      attempt at home chemotherapy with UFT + LV by oral administration, in
      consideration to the convenience of patients. SUBJECTS: The subjects of this
      study were 24 post-operative patients who had been assessed with Dukes D and
      curability C colorectal cancer with measurable metastatic lesions and who could
      tolerate chemotherapy. METHODS: 1 course of treatment consisted of 2 weeks of UFT
      at 300-400 mg/m2/day and LV at 15 mg/body/day followed by 2 weeks of drug
      withdrawal. The administration was conducted for 4 courses or more as the target.
      Unless serious adverse reaction occurred, dose increase of UFT was allowed.
      RESULTS: The efficacy rate in the 22 patients who were assessable was 22.7%.
      There were 11 NC patients, accounting for half (50%) of the subjects. This home
      chemotherapy is expected to become an alternative chemotherapy against colorectal
      cancer in the future, because the treatment does not require hospitalization and
      has less impact on the QOL of patients.

PMID- 15170992
TI  - [A case of colon carcinoma with unresectable multiple liver metastases responding
      to various combined chemotherapies centering on hepatic arterial infusion
      therapy].
AB  - We have experienced a case of colon carcinoma with unresectable multiple liver
      metastases responding to various combined chemotherapies centering on hepatic
      arterial infusion therapy. A 42-year-old female with descending colon carcinoma
      and synchronous unresectable multiple liver metastases underwent left
      hemicolectomy in September 2001. She was treated with chemotherapy centering on
      hepatic arterial infusion (HAI) following implantation of a reservoir in the
      outpatient setting. Pharmacokinetic modulating therapy (PMC), and HAI with
      Leucovorin/CDDP/5-FU and Levoforinate/CDDP/5-FU were conducted sequentially.
      Alternative HAI of 5-FU with intravenous infusion of Levoforinate and systemic
      irinotecan/CDDP were continued biweekly after release of the hepatic artery
      occlusion. Liver metastases shrunk after 6 months of treatment and were
      remarkably decreased in size in May 2003. Although 3 metastatic lesions existed
      in both lungs, good quality of life has been maintained in the 2 years following
      surgery.

PMID- 15170994
TI  - [Intra-arterial docetaxel chemotherapy with high-dose calcitriol in relapsing
      metastatic prostate cancer].
AB  - Ten patients with hormone relapsing metastatic prostate cancer who had been
      previously treated with extensive radiotherapy for metastasis and chemotherapy
      including docetaxel and platinum compounds were evaluated to determine the safety
      and efficacy of docetaxel with high-dose calcitriol and platinum compound
      combination intra-arterial chemotherapy. Nine patients with ECOG performance
      status 3 or greater, and 9 with 12-month survival probability less than 0.5 in
      the CALGB prognostic model, including 3 aged over 80, were assessable for
      therapeutic results, adverse events and clinical benefit response. Improvement of
      QOL and relief of the bone pain were seen immediately after the intra-arterial
      chemotherapy treatment. Considering that high-dose calcitriol and platinum
      compound combination intra-arterial chemotherapy is easily administered without
      major toxic events even to outpatients, it will be a treatment option for the
      clinical benefit of relapsing prostate cancer patients with poor prognoses.

PMID- 15170993
TI  - [A case of hepatocellular carcinoma with bone metastasis responding to concurrent
      TS-1/low-dose cisplatin (CDDP) therapy and radiotherapy].
AB  - A standard treatment for hepatocellular carcinoma with extrahepatic metastasis is
      not established and chemotherapy is ineffective. We experienced a case of
      hepatocellular carcinoma with bone metastasis that responded to concurrent TS
      1/low-dose cisplatin (CDDP) therapy and radiotherapy. A 58-year-old male patient
      with left iliac bone metastasis after 2 hepatectomies was admitted to our
      hospital. The titer of serum AFP and PIVKA-II showed an extremely high levels,
      12,350.5 ng/ml and 993 mAU/ml, respectively. The uptake area was found at the
      left iliac bone by scintigraphy with 99mTc-HMDP. Treatment with TS-1/low-dose
      CDDP therapy and radiotherapy (36 Gy) was started concurrently. The chemotherapy
      regimen comprised daily oral administration of 100 mg of TS-1 for 21 days and
      CDDP 10 mg/body infusion (day 1-5, 8-12). An additional 2 courses of TS-1/low
      dose CDDP therapy were repeated. After that, severe pain diminished and the titer
      of serum showed AFP and PIVKA-II had improved to within normal ranges. The uptake
      at the left iliac bone was found to have decreased by scintigraphy. Adverse
      events were grade 1 nausea and leucopenia. TS-1/low-dose CDDP therapy seems to be
      applicable for the treatment of hepatocellular carcinoma with bone metastasis.

PMID- 15170995
TI  - [Multidisciplinary treatment for advanced bladder cancer--a case report].
AB  - The patient was a 63-year-old woman who had been diagnosed with advanced bladder
      cancer with renal dysfunction and bilateral bulky pulmonary metastasis.
      Initially, the primary lesion was resected and the implantation of an infusion
      catheter and port system was performed. Following surgery, she received
      intermittent intra-arterial (IA) low-dose CDDP chemotherapy via the infusion port
      and concurrent bronchial arterial infusion and radiation (40 Gy for the left
      lung). About 3 months later, the right and left lung metastases were reduced 63%
      and 91%, respectively, and a right lower lobectomy was performed. CDDP was
      administered through the outpatient clinic ever since. From January 2001, we
      began to use docetaxel (TXT) for CDDP because of continuous grade 2 nausea and
      appetite loss. There were no adverse effects by TXT. Repeated IA chemotherapy was
      discontinued from June 2001 because of neurological symptoms. In September 2001,
      a left skull base metastasis was detected and was treated by radiation 40 Gy. In
      November 2002, a left patella metastasis appeared and was treated by IA
      chemotherapy with angiotensin II and radiation 30 Gy. We confirmed that
      multidisciplinary treatment contributed to her approximately 3-year survival with
      good QOL. The cancers in both lungs could be kept under control until her death.

PMID- 15170997
TI  - [Lymph nodes mapping for detection of sentinel nodes in patients with papillary
      thyroid cancer].
AB  - We examined the feasibility of sentinel lymph node biopsy for papillary thyroid
      cancer. In the dye injection method, 1% of isosulfan blue dye was injected around
      the tumor of 32 patients intra-operatively, and in the radioisotope (RI) colloid
      injection method, 99mTc-tin colloid was injected in 23 patients 1 day
      preoperatively. Lymph node mapping for detection of sentinel nodes was performed
      after thyroidectomy and central and modified lateral neck lymph node dissections.
      All dissected nodes were examined postoperatively by hematoxylineosin staining to
      determine whether or not metastasis was present. In the dye injection method,
      sentinel lymph nodes were identified in 30 (94%) of the 32 patients. Lymph node
      metastases were found in 14 patients, and some sentinel lymph nodes had papillary
      cancer metastasis in 13 patients. There was only 1 false-negative case.
      Sensitivity and accuracy of sentinel lymph node biopsy was 93% (13/14) and 97%
      (29/30). With the RI method, detection rate, sensitivity and accuracy of sentinel
      lymph node biopsy was 96% (22/23), 90% (9/10) and 95% (21/22), respectively. Our
      preliminary study indicated that sentinel lymph node biopsy was feasible in
      patients with thyroid cancer. It may be helpful in avoiding unnecessary lymph
      node dissection and improving quality of life in patients with thyroid cancer.

PMID- 15170996
TI  - [Chemoradiation using 5-fluorouracil (5-FU) and nedaplatin (NDP) for
      gynecological malignancy--the relation between hemotoxicity and sequence of 5-FU
      and NDP].
AB  - We compared sequence-dependent schedules of 5-fluorouracil (5-FU) and nedaplatin
      (NDP) for hemotoxicity in genecological malignancy (GM). The safety of schedules
      using 5-FU before/after NDP combined radiotherapy in 8 patients with GM was
      evaluated. They received either 5-FU 700 mg/m2 i.v. continuous infusion on days
      (D) 1-4 + NDP 100 mg/m2 i.v. bolus on D1 (group A: 5 pts), or NDP on D4, 5-FU on
      D1-4 (group B: pts). In group A, 4 patients received a reduced dose of NDP
      because of less than 60 ml/min of creatinine clearance. In group A, WBC (2 pts),
      hemoglobin (3 pts), and platelet (1 pts) were grade 3 or higher. In group B,
      grade 3 or higher in hemotoxicity was not seen. A higher percentage of
      hemotoxicity was seen in group A compared with group B.

PMID- 15170998
TI  - Tolerogenic properties of dendritic cells in allografting.
AB  - In this review we present current views on the mechanism of prolongation of organ
      allograft survival mediated by donor dendritic cells. The contemporary research
      focuses on problems as: a) is the DC microchimerism the cause or consequence of
      long-term graft acceptance, b) what is the role of DCs, which are derived from
      bone marrow, with respect to the cell trafficking and dissemination and site
      specific function as related to the mechanism of tolerance. There is a large body
      of evidence indicating that DC play certain regulatory role in the process of
      induction of tolerance. Immaturity of DCs, bone marrow lineage, method of
      dissemination by infusion in suspension or from the vascularized bone marrow
      graft, location after transplantation and environment inhibiting their maturation
      seem to be the prerequisites for displaying their tolerogenic activity. The
      subtle balance between induction of tolerance or immunization does not allow
      today to use immature DC in clinical practice. Further studies, in particular in
      human recipients, are needed.

PMID- 15171000
TI  - Solid organ transplantation and HIV infection.
AB  - HIV infection has been traditionally considered to be an absolute
      contraindication for solid organ transplantation. Recent advances in HIV
      treatment, as highly active antiretroviral therapy (HAART), significantly reduced
      HIV-related mortality and morbidity. At the same time the number of HIV-infected
      patients with end-stage organ diseases constantly increased. Current data
      describing solid organ transplantation in HIV-infected patients demonstrated
      comparable outcome to that in the HIV-negative population. In light of this,
      solid organ transplantation should be considered as a treatment option for
      selected HIV-positive patients with end-stage organ disease.

PMID- 15170999
TI  - Immune changes in lymph nodes after skin grafting. I. Effects of bacterial
      antigens.
AB  - Transplantation of skin brings about response of the regional lymph nodes. Lymph
      node cells (B and T lymphocytes, dendritic cells, imigrating monocytes, high
      endothelial venous cells) respond to three types of antigens: allogeneic,
      bacterial and self-antigens. Allogeneic reaction is induced by contact of antigen
      presenting cells (APC) with donor antigens. Bacteria penetrate rejecting graft
      epidermis and travel along lymphatics to the nearest lymph node. Rejecting graft
      debris is phagocytized by macrophages and dendritic cells and transported to
      lymph nodes. These different type antigens induce different reaction of node
      cells. In this review we present data from literature and own studies on the
      effect of bacteria normally residing on skin surface on lymph node after
      penetration of epidermis. Further reviews will be dealing with the response of
      lymph nodes to allo- and autoantigens.

PMID- 15171001
TI  - The Fc gamma RIIa polymorphism in patients with acute kidney graft rejection.
AB  - The Fc gamma RIIa receptors are the most widely distributed of the three classes
      of Fc receptors and expresses an allelic polymorphism. This polymorphism may
      modulate the immune response and may be a factor for some diseases. The aim of
      the study was to evaluate the association between the Fc gamma RIIa polymorphism
      and acute kidney graft rejection. The study was carried out in 115 kidney
      allograft recipients. The frequency of acute kidney graft rejection was similar
      in relation to Fc gamma RIIa genotypes. We suggest that Fc gamma RIIa
      polymorphism is not important risk factor for acute kidney graft rejection
      susceptibility.

PMID- 15171003
TI  - Assessment of early graft function in relation to different preservation fluids-
      preliminary results.
AB  - The parameters of transplanted liver functions were exposed to a retrospective
      analysis during the past year. A group of 51 patients out of 223 were thoroughly
      examined, all of them having undergone orthotopic liver transplant in Department
      of General, Transplant and Liver Surgery, Medical University of Warsaw until
      1.09.2003. With transplants, two types of preservation fluids: UW (Viaspan) and
      Celsior were used alternatively. Liver function was assessed on the basis of the
      clinical feature and biochemical data. The results obtained were statistically
      verified. The way of fluid perfusion during the operation and the rinsing
      effectiveness were also evaluated, additionally the level of marked K during the
      reperfusion was checked. There were no statistically significant differences
      noticeable between both groups of recipients. Among all the liver and kidneys
      effectiveness parameters assessed with the recipients after OLTx, the
      considerable difference statistically, was visible only with the levels of AspAt,
      AlAt, INR and APTT during the first days and nights after the operations. Later
      the difference was gradually disappearing. However, in accordance with the
      harvesting teams' opinions, the usage of Celsior, owing to lower viscosity,
      allowed for faster and more exact blood rinsing from a vascular bed of the organ
      transplanted. The organ's even penetration was also possible. The lack of
      necessity to use additional stabilizers also simplified radically the harvesting
      technique. Celsior--the preservation fluid used in the authors' clinic meets all
      the requirements necessary to efficacious preservation and storage of a to be
      transplanted liver.

PMID- 15171002
TI  - Similar response of dendritic cells to bacterial and allogeneic antigens.
AB  - The dendritic cells (DC) of an allograft recipients become engaged not only in an
      allogeneic but also antibacterial reaction. They react to the alloantigens and
      microorganisms which colonize the rejecting grafts. This leads to overstimulation
      of DCs what may non-specifically intensity the rejection process. We investigated
      the effects of allogeneic and bacterial antigens on splenic DCs phenotypes. In
      vitro stimulation of spleen DC-enriched population by E. coli, LPS and CpG DNA
      brought about an increase in expression of OX6 (MHC class II) from 47.4% in the
      control population to 65% in the E. coli stimulated group (p < 0.05) and to 85%
      in the LPS and CpGDNA groups (p < 0.05). Interestingly, a significant drop in the
      frequency of OX62+ antigen was observed after incubation with LPS. Allogeneic
      heart transplants brought about an increase of OX6+ (MHC class II) DCs to 100%
      and a decrease of EDI+ cells. Simultaneously, an increase in expression of W3/13
      on DC-enriched splenic cells was observed. There was no significant change in the
      frequency of OX62+ expression in conclusion, both bacterial and alloantigens
      strongly activate splenic DCs what may add to the intensity of the rejection
      process.

PMID- 15171004
TI  - Model of small bowel transplantation with systemic venous drainage in rats.
AB  - Authors in details describe microsurgical technique of heterotopic small bowel
      transplantation (SBT) with systemic venous drainage in rats. Surgical technique
      was practiced on laboratory Wistar rat (n = 40), male with weight 240-300 g. This
      paper in details analyzes the surgical procedure and includes methods of
      anesthesia, organ harvest, methods of conservation, transplantation and their
      complications. The aim of authors is to describe a reproducible model of small
      bowel transplantation in rat and to get a basis for next experimental studies,
      which will investigate others aspects of SBT like preservation-reperfusion injury
      and immunological aspect as rejection. Five days of surviving of rats was
      accepted as successful.

PMID- 15171005
TI  - Perioperative use of recombinant activated factor VII in liver transplantation.
AB  - Recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Denmark)
      is a treatment used to prevent and arrest intra- and postoperative bleeds in
      patients with haemophilia A or B complicated by circulating anticoagulants
      (inhibitors of FVIII and FIX). Patients who qualify for liver transplantation may
      have varying degrees of coagulation impairment, which may adversely impact
      elective anaesthetic and surgical procedures and elevate the risk of
      intraoperative bleeds, which require massive blood transfusions and worsen
      prognosis. Recently, reports have been published on the use of rFVIIa prior to
      surgical procedures, which are likely to cause severe blood loss as well as for
      so-called emergency therapy of coagulation disorders during liver
      transplantation.

PMID- 15171006
TI  - Transplantation procedures in social awareness opinion poll of Silesian Province
      citizens on living donor organ transplantation.
AB  - OBJECTIVE: The aim of the study was to examine the opinion of Silesian Province
      citizens on living organ transplantation (Tx). METHODS: The materials in the
      study were the opinions of 1100 respondents selected from a representative group
      of adult citizens collected in 2002 using a public opinion poll. During the data
      collection a questionnaire interview was used, the result of which were subjected
      to a quantitative statistical analysis. RESULTS: Of respondents, 83.1% do but
      11.0% do not accept living organ Tx. 92.1% would give his organ for Tx to a
      relative, 80.5%--a friend and 54.3%--a strange person. The most common motives of
      potential agreement for living organ donation are awareness of helping another
      person (43.6%) or a relative (27.0%) as well as conviction of safety of organ
      harvesting procedure (10.0%). The most common motives of concern are fear of
      losing one's health (40.1%), poor state of health (13.8%) and fear of organ
      harvesting (9.8%). CONCLUSIONS: Silesian Province citizens accept living organ Tx
      as a way of treatment of patients with end stage organ failure. The main motive
      of agreement for living organ donation is awareness of helping another person or
      a relative, and the most common motive of concern is fear of losing one's health.

PMID- 15171007
TI  - Application of biological dressings from radiosterilized amnios with cobalt 60
      and serologic studies on the handling of burns in pediatric patients.
AB  - We present the use of biological dressing (amnios) as an alternative for skin
      replacement due to burn accidents. With the use of serologic tests, it is
      guaranteed to be free of the possibility of transmitting infectious diseases. The
      amnios is sterilized with 60Co gamma radiation. In this way, amnios is free of
      bacteria and fungi. In addition, with the use of serologic tests at the moment of
      the childbirth and 6 months later, we can be sure that it won't transmit the
      syphilis, AIDS, hepatitis b and c viruses. This treatment was applied to 12
      children with burns of 1 degree  and 2 degrees degree (7 girls and 5 boys) that
      required hospitalization. The application is very simple. It does not require of
      anesthesic procedure, or the use of surgical room. The pain decreased
      notoriously, and the procedure can be repeated as frequently as necessary. Once
      the dressing is applied, it does not require any type of surgical cleaning. The
      scaring process begins at the borders and under the dressing, where there is a
      new tissue. It decreases: 1) the possibility of infection, and therefore reduces
      the consumption of antibiotic; 2) the use of analgesics; 3) the time of scaring
      and 4) the number of days of hospitalization.

PMID- 15171009
TI  - Risk factors of gingival overgrowth in kidney transplant recipients treated with
      cyclosporine A.
AB  - OBJECTIVES: Gingival overgrowth is a common side effect of cyclosporine A (CsA)
      therapy. The pathogenesis of CsA-induced gingival overgrowth is still debated.
      The influence of CsA dosage and its trough level, HLA phenotype, gender and the
      administered calcium channel blocker on incidence and severity of overgrowth were
      studied. Moreover, relationship of overgrowth with plasma level of TGF-beta I was
      assessed. METHODS: Degree and extent of gingival overgrowth were tested in 124
      kidney transplant recipients treated with CsA, in 9 patients treated with
      azathioprine and in 21 patients treated with tacrolimus, and various calcium
      channel blockers. RESULTS: Gingival overgrowth was found in 46% of patients
      treated with CsA. Total yearly CsA dosage was significantly higher in patients
      with overgrowth. Gingival overgrowth was observed in: 86% of patients treated
      with nifedipin, 47% with amlodipine, 35% with verapamil. HLA-DR antigens analysis
      showed that half of the patients with DR-2 allele suffered from overgrowth.
      Gingival overgrowth was found twice as often in males than in females. Plasma
      level of TGF-beta I was similar in patients with or without overgrowth. Gingival
      overgrowth was not found in patients treated with azathioprine or tacrolimus
      despite that half of the patients received nifedipine or amlodipine. CONCLUSIONS:
      The study revealed high frequency of overgrowth in renal graft recipients treated
      with CsA. Overgrowth severity was larger in patients treated simultaneously with
      nifedipine or amlodipine. CsA dosage, male sex and HLA-DR2 phenotype were risk
      factors of gingival overgrowth. None of the patients treated with tacrolimus
      suffered from gingival overgrowth.

PMID- 15171010
TI  - Investment in employees helps NY hospital boost productivity.

PMID- 15171011
TI  - Performance-based programs gain ground, offer 'real dollars' to providers.
AB  - Performance-based physician incentive plans are proliferating, with more than
      four dozen initiatives now covering more than 30% of all HMO and PPO members
      across the U.S. Health plans that have implemented pay for performance programs
      see them as an important business strategy for improving health care quality
      while meeting a variety of other goals.

PMID- 15171008
TI  - Early results of a new liver transplant program in Szczecin, Poland.
AB  - New liver transplant programs have usually been associated with a significant
      learning curve. This learning curve, however, can be minimized or avoided if
      certain conditions are met. In this paper we describe the establishment of a new
      liver transplant program in Szczecin, Poland and present its early results. Four
      members of the team underwent training in clinical liver transplantation in major
      centers in Europe. Transplant protocols were then adopted, all the necessary
      facilities set up, and multidisciplinary team created. Between February 2002 and
      August 2003, 22 adult orthotopic liver transplantations (OLT) were performed in
      21 patients (13 male; mean age 46.3 years; range 33-62), including I retransplant
      for early hepatic artery thrombosis. Eighteen (86%) patients are alive between 4
      and 22 (median 11) months after OLT. Seventeen patients have normal liver
      function and 14 of them have resumed full life activity. Three patients died: one
      of bacterial peritonitis (day 6), one of chronic rejection with allograft failure
      (month 4) and one following massive stroke (month 10). Surgical complications
      occurred in 7 patients (33%). We believe that proper training of vital team
      members at established transplant centers with good results, availability of
      adequate equipment and all the facilities required with strict adherence to
      transplant protocols are all paramount for a successful start of a liver
      transplant program.

PMID- 15171012
TI  - Internet scheduling takes the paper out of making appointments.
AB  - Paper appointment books are being tossed in the trash at some health care
      organizations, as they discover that using Internet-based systems to schedule
      patients is a more efficient process.

PMID- 15171013
TI  - [The pre-excitation ventricular syndrome in 115 cases].

PMID- 15171014
TI  - A child with recombinant of chromosome 8 inherited from a carrier mother with a
      pericentric inversion.

PMID- 15171015
TI  - [Serum level of parathyroid hormone, albumin and calcium in patients with
      proximal femoral fracture].

PMID- 15171016
TI  - [The relationship between antithyroglobulin antibodies and the evolution of
      thyroids diseases].

PMID- 15171017
TI  - Renal acidification in hyporeninemic hypoaldosteronism.

PMID- 15171018
TI  - Effect of an accidental exposure to dimethoate and derivatives.

PMID- 15171019
TI  - Effect of prostaglandins on renin release from rat renal cortical slices.

PMID- 15171020
TI  - [Relapses in pulmonary tuberculosis. Value of the case history for the selection
      of the best retreatment regimen].

PMID- 15171021
TI  - [Selective hypophysectomy in 11 patients with Cushing's disease].

PMID- 15171022
TI  - [Immunogenetic study of tumor growth in inbred rats].

PMID- 15171024
TI  - [Production of a glycoprotein by T lymphocytes in Chagas cardiomyopathy].

PMID- 15171023
TI  - Prenylamine inhibition of adriamycin-induced cardiomyopathy in mice.

PMID- 15171026
TI  - [Shock, severe metabolic acidosis and chronic alcoholism].

PMID- 15171025
TI  - [Changes in the effect of verapamil by the influence of autonomic reflex].

PMID- 15171028
TI  - [Hyperkalemia in the chronic renal failure: is it always the aldosterone the
      responsible?].

PMID- 15171027
TI  - [Importance of the retinoids in malnutrition, the immune response in cancer].

PMID- 15171029
TI  - [Considerations on septic shock].

PMID- 15171030
TI  - [A "divine" medication].

PMID- 15171031
TI  - [Renaissance of psychiatric diagnosis].

PMID- 15171032
TI  - [The treatment of war neurosis].

PMID- 15171034
TI  - [Lymphatic vessels and regional lymph nodes of the lung (pathways of lymph
      outflow from the lung)].

PMID- 15171033
TI  - [Radiation techniques for detection and diagnosis of tuberculosis today].

PMID- 15171035
TI  - [Relapses of respiratory tuberculosis].

PMID- 15171036
TI  - [Sociomedical features of new cases of tuberculosis].

PMID- 15171037
TI  - [Changes in disability rates in patients with tuberculosis in Moscow (1997
      2001)].

PMID- 15171038
TI  - [Vascular endothelial dysfunction in patients with chronic obstructive lung
      diseases].
AB  - At present data on endothelial dysfunction in chronic obstructive lung diseases
      (COLD) are lacking while in these diseases, favorable conditions are being
      established to develop endothelial dysfunction, namely: hypoxia, metabolic
      dysfunction of the lung endothelium, elevated levels of different biologically
      active substances, including cytokines, leukotrienes, etc. Sixty males with COLD,
      whose mean age was 51.16 +/- 1.13 years, were examined. A control group comprised
      35 apparently healthy volunteers. Reactive hyperemia and nitroglycerin tests were
      performed to study endothelial function. The blood levels of desquamated
      endotheliocytes were determined by the method described by J. Hladovec (1978).
      According to the findings, the count of circulating endothelial cells was greater
      in patients with COLD than that in healthy individuals. In patients with severe
      COLD, the signs of endothelial lesion were most pronounced than in those with
      mild and moderate COLD. Patients with COLD showed a significantly lower level of
      current-dependent dilatation than did the controls. At the same time, patients
      with severe COLD exhibited a more marked decrease in endothelium-dependent
      dilatation than did those with mild and moderate COLD. Thus, patients with COLD
      have been found to have signs of endothelial lesion and impairments of the
      vasoregulatory activity of the vascular wall, which require further studies.
      These changes manifest themselves just in patients with mild and moderate COLD
      and they are most marked in patients with severe COLD.

PMID- 15171040
TI  - [Destructive pneumonia of syphilitic etiology].

PMID- 15171039
TI  - [Spoligotypes of clinical Mycobacterium tuberculosis strains isolated in patients
      with tuberculosis in the Central Region of Russia].
AB  - Spoligotyping and RFLP-IS6110 techniques were used to analyze 353 clinical
      Mycobacterium tuberculosis strains isolated from patients with tuberculosis in
      the Central Region of Russia. All spoligotypes were classified according to the
      international database. Most clinical M. tuberculosis strains in the collection
      obtained from patients living in the Central Region of Russia belong to the LAM
      (49.6%) and Beijing (34%) families, as shown by spoligotyping, and to A1 (51.3%)
      and W (34%) families, as evidenced by the RFLP-IS6110 technique.

PMID- 15171041
TI  - [Significance of determination of drug resistance in Mycobacterium tuberculosis
      for successful treatment of pulmonary tuberculosis].

PMID- 15171042
TI  - [RF Health Ministry Order No. 109 "On improvement of tuberculosis preventive
      measures in the Russian Federation" dated March 21, 2003 (continued, its
      beginning in No. 11, 2003].

PMID- 15171043
TI  - [Abdulla Mukharramovich Ubaidullaev].

PMID- 15171044
TI  - [Efficacy of vaccination in the adjuvant treatment of cancer of the kidney].

PMID- 15171045
TI  - [In patients with cancer of the larynx, chemoradiotherapy with cisplatin is
      superior to neoadjuvant chemotherapy followed by radiotherapy and to exclusive
      radiotherapy].

PMID- 15171046
TI  - [Troxacitabine].
AB  - Nucleoside analogues are commonly used in the treatment of hematological
      malignancies and solid tumors. As antimetabolites, these drugs act by disrupting
      DNA synthesis and inducing apoptosis following their incorporation into DNA.
      Troxacitabine (Troxatyl) is the first nucleoside analogue with anticancer
      activity that has an unnatural stereochemical configuration. Its broad
      preclinical antineoplastic spectrum led to its clinical development. Summaries of
      the preclinical data and of the initial phase I and II clinical trials are
      presented.

PMID- 15171047
TI  - [Identification and management of hereditary predisposition to cancer of the
      breast and the ovary (update 2004)].
AB  - BACKGROUND: Since the last recommendations, up to 2,500 new references had been
      published on that topic. METHODOLOGY: On the behalf of the health Minister, the
      Ad Hoc Committee consisted of 13 experts carried out a first version revisited by
      five additional experts who critically analyzed the first version of the report.
      MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer
      deleterious mutation of BRCA12 and BRCA2 than previously thought. The screening
      of ovarian cancer is still not an attractive option while in contrast MRI may be
      soon for these young women with dense breast, the recommended option for breast
      cancer screening. The effectiveness of prophylactic surgeries is now well
      established. French position is to favor such surgeries with regard to a quality
      of life in line with the expected benefit, and providing precise and standardized
      process described in the recommendation. CONCLUSIONS: Due to methodological
      flaws, the low power and a short follow-up of the surveys, this statement cannot
      however aspire to a high stability.

PMID- 15171048
TI  - [Impact of regulations on translational research in cell and gene therapy: the
      American experience].
AB  - The increasing utilization of cell and gene therapy in the treatment of human
      diseases, particularly cancers, has led lawmakers to institute stringent rules to
      regulate this new area of medicine and optimally protect patients. Cell and gene
      therapy centers, often located within academic institutions, are becoming subject
      to rules previously applied only to pharmaceutical companies. Based on the US
      experience, we review here the regulations that currently regulate or are being
      proposed to cover cell and gene therapy centers. We describe the principles of
      good manufacturing practices, quality assurance and quality control and
      accreditation. Finally, we discuss the future of cell and gene therapy in the
      context of the increasingly rigorous regulatory environment implemented in the
      US.

PMID- 15171049
TI  - [Cancer, a defect of the psyche?].
AB  - Patients and families often put forward psychosocial determinants to explain
      occurring or progression of cancer disease. The idea of a psychogenesis in cancer
      is widely spread by the surrounding culture. Nevertheless, the scientific
      research in this field brought very contradictory results, and often rests on
      debatable methods. Some authors hypothesize that a type C personality predisposes
      to cancer. But so far, most of prospective studies analysing the association
      between C traits and this disease have been negative. Results of semi-prospective
      studies, in which patients are enlisted before a diagnostic investigation, are
      difficult to interpret, because the starting features can partly result from the
      stress of this investigation. The same problem interferes with most studies about
      the association between alexithymia and cancer. The reliable works analysing the
      impact of depression most often conclude in favour of a non-existent or a weak
      risk, and do not allow defining it as a well established risk factor. Most of
      prospective studies about the link between stress and cancer are negative.
      Moreover, they index stressful life events occurred for a few years before the
      diagnosis, that is to say during a too short delay to be allowed to incriminate
      them in the supervening of the disease. The question of the possible impact of
      coping styles with cancer on its evolution also remains debated. Some studies for
      instance plead in favour of a beneficial effect of fighting spirit or denial, but
      they are contradicted by other studies. All this forces us to be very careful
      when discussing the possible links between psyche and cancer. It is important to
      underline the hypothetical nature of these relationships. Psychosomatic
      explanations risk to be used to fill in gaps of knowledge, and to give us the
      illusion that we can avoid or control a disease which escapes us. They especially
      risk to make the patients guilty of their cancer or its evolution, through an
      inadequate point of view which does not take the complexity in stake into
      account.

PMID- 15171050
TI  - [Docetaxel and gastric cancer].
AB  - There are very few active drugs in the treatment of metastatic gastric carcinoma.
      Among new drugs, docetaxel has shown one of the most important activity. With
      precise evaluation of objective response, this drug has demonstrated a 20%
      response rate in monotherapy. The favorable toxicity profile of this compound
      allowed combination therapy with other active drugs in this disease: 5
      fluorouracil (5FU), cisplatin and epiadriamycin. Two of the most interesting
      combinations are: bitherapy with docetaxel cisplatin and three therapy with
      docetaxel, continuous infusion of 5FU and cisplatin (TCF). Several large phase
      III trials are on-going to compare these new schedules to classical combination
      chemotherapies of this disease (5FU cisplatin or ECF). The potential place of
      docetaxel in gastric cancer is not restricted to metastatic disease and the same
      three-therapy with TCF is currently under evaluation as a neoadjuvant or adjuvant
      treatment in resectable lesions. With a high activity in terms of
      radiosensitization, docetaxel could also become a major drug in the design of new
      radiochemotherapy protocols for neoadjuvant or adjuvant disease.

PMID- 15171051
TI  - [Docetaxel and non-small cell lung cancer].
AB  - Docetaxel (Taxotere) is a taxoid used in various tumoral diseases. Its role in
      metastatic or locally advanced non small cell lung cancer treatment is
      undeniable. In pretreated patients with metastatic NSCLC, two recent phase III
      trials have shown an improvement of survival and quality of life for patients
      receiving docetaxel. In front line treatment, docetaxel administered alone every
      three weeks or in combination with a platine compound has became a gold standard
      treatment. Activity of the associations cisplatinium/docetaxel and
      carboplatin/docetaxel is similar to those reported with previous combinations
      containing a platine derivative. The weekly schedule of docetaxel and its
      combination with other well known active drugs in NSCLC such as gemcitabin or
      vinorelbin deserve further evaluations. Therapeutic options with docetaxel in
      adjuvant situation in resected NSCLC or in combination with radiation therapy in
      operable locally advanced NSCLC should be developed in the next future.

PMID- 15171052
TI  - [Demography of oncologic practitioners working in France. Projection elements for
      the next 30 years].
AB  - In the early eighties, French medical regulatory authorities have decided to
      control the access to medical studies by restricting the number of admittances.
      From that date, the numerous clauses was unchanged, leading the physicians to
      observe a deep reduction in the number of young oncologists. The goal of this
      study was to define precisely the demography of French medical oncologists and
      the needs for new specialists. Our model used data from a wide range of sources
      was developed under the guidance of epidemiologists. We determined current and
      projected numbers and demographics of oncologists in France workforce from 2002
      to 2032. The number of oncologists and physicians implicated in oncology (organ
      specialists, radiotherapists and paediatricians) entering the marked in the next
      few years will not be modified. Consequently, the number of physicians will
      dramatically decrease in the next 15 years resulting in a 25% global working-age
      population reduction. Our present analysis indicates that the number of
      oncologists will not be sufficient to meet future demand. Our data suggests that
      steps should be taken to stop the ongoing decline in the number of physicians
      involved in oncology and the decline of physicians in training. Consideration
      should be given to actions designed to increase the number of oncologists in
      practise in the years ahead.

PMID- 15171053
TI  - [A study of the social representations in chemotherapy: a way to analyse the
      relations between patients and oncologists].
AB  - This research aims to study social representations throughout chemiotherapy, out
      of a population composed of doctors specialized in Oncology on one hand, and
      patients dealing with cancer during their chemiotherapy on the other hand. Our
      methodology is situated among quantitative methods using SPSS for Anovas to
      analyze statistics datas, EVOQ and Alceste for the pragmatic analysis of the
      discourse. The datas were collected from a questionnaire including items and
      words associations. We were interested in chemiotherapy which appears as a social
      object likely to generate a representative process from which emerges a serie of
      adaptative strategies belonging to both cognitivo-behaviourism and emotional
      spheres. chemiotherapy leads to an adaptation of the patient and remains a
      mediator in the doctor-patient's relation. As far as representations are "action
      guides", the existence of a representation specific to patients and doctors,
      allowes us to point out, through a semantic and emotional gap a technical
      medicine which is, in the future, likely to tend to existentialism.

PMID- 15171054
TI  - [Charles Oberling (1895-1960)].

PMID- 15171056
TI  - Balancing work and studies: another factor complicating nursing shortages.

PMID- 15171057
TI  - [The impact of a case management approach for total hip and knee arthroplasty
      patients].
AB  - The primary goal of this research was to evaluate the impact of introducing a
      case management approach for total hip (THA) and knee (TKA) arthroplasty
      patients, on the number of complications, visits to the emergency clinic and
      readmissions, as well as on length of stay (LS). The period covered by this
      retrospective study was fiscal 1999-2000. Subjects were divided into an
      experimental group, with the case management, and a control group receiving the
      usual care. The second goal of the research was to compare these groups with non
      equivalent groups from fiscal 1996-1997, before case management was introduced.
      The reference framework used is the case management model in the institution. All
      in all, 256 files (52%) were reviewed. We found that the LS, for THA and TKA
      cases in the hospital where the experiment was done, had decreased considerably
      three years after case management was introduced, and that this reduction was
      also significant for TKA cases in comparison with the non-case management group
      at the control group hospital, without compromising certain clinical results.

PMID- 15171063
TI  - [Screening for spousal abuse: the nurse's role].

PMID- 15171064
TI  - [A story of heart and teamwork].

PMID- 15171065
TI  - Standardized pill imprint codes: a pharma fantasy.
AB  - To safely use medications, professionals and consumers need usable and reliable
      methods to identify tablets patients are prescribed and taking. Currently, each
      manufacturer assigns its own identifying codes and symbols. Standardization of
      the system for identifying solid dosage forms is a goal that has been widely
      advocated, yet stubbornly resistant to progress. Physicians, pharmacists, and
      consumers attempting to identify pills must use various methods which have
      shortcomings in ease of use, availability, and accuracy. Arguments have been
      advanced, particularly by pharmaceutical manufacturers, that evidence of
      unworkability of the current system is not compelling, and costs of retooling
      current manufacturing processes could be prohibitive. These issues are currently
      being explored by a task force led by the U.S. Pharmacopeia Safe Medication Use,
      and Pharmaceutical Forms Dosage Expert Committees. This paper presents a
      fictitious case study of an elderly patient succumbing to digoxin overdose
      illustrating the dilemmas posed in the tablet-imprint debate.

PMID- 15171067
TI  - A system for multiattribute drug product comparison.
AB  - We describe a system for multiattribute drug product searching. We then
      demonstrate the system's performance on sample queries, and evaluate the name
      based similarity searching component. Ten drug names were used to query a
      database of existing drug names using five different retrieval methods. Retrieved
      names were merged into master lists and presented to 15 pharmacists. Pharmacists
      rated the similarity between the query name and each retrieved names on a scale
      of 1-5. We report the precision of our five different retrieval methods at 11
      levels of recall. The best single measure was editex, with a precision of 17.4%
      averaged across 11 levels of recall. A regression model using four objective
      measures of similarity as predictors accounted for 40.6% of the variance in
      observed mean similarity ratings. Automated, multiattribute drug product
      searching may improve the effectiveness and efficiency of preapproval screening
      processes and thereby prevent medication errors.

PMID- 15171066
TI  - Reducing medication errors through naming, labeling, and packaging.
AB  - Errors due to look-alike or sound-alike medication names are common in the United
      States, and are responsible for thousands of deaths and millions of dollars in
      cost each year. Up to 25% of all medication errors are attributed to name
      confusion, and 33% to packaging and/or labeling confusion. Thousands of
      medication name pairs have been confused based on similar appearances or sounds
      when written or spoken, or have been identified as having the potential for
      confusion. Systems and recommendations have been developed that may reduce the
      occurrence of such errors.

PMID- 15171068
TI  - Introducing new technology: handheld computers and drug databases. A comparison
      between two residency programs.
AB  - There have been numerous efforts to introduce and increase the use of handheld
      computers, also called personal digital assistants (PDA), in health care, one of
      which is the distribution of PDAs to Neurology residents at the University of
      Illinois at Chicago. The authors examined the success of this intervention by
      comparing PDA use and user attitudes between residents of the intervention group
      and residents in another residency program where the use of PDAs is neither
      encouraged nor discouraged. The authors examined in particular the use of drug
      databases on the PDA as its currently most popular application in health care.
      The use of PDAs for purposes not related to health care was widespread among
      individuals in both programs, but the use of drug databases was significantly
      more common in the control group, which can be interpreted as a success of the
      intervention.

PMID- 15171069
TI  - The pharmacist shortage and medication errors: issues and evidence.
AB  - The paper, as part of this special issue in error prevention, reviews and
      discusses evidence in the literature related to the impact of the pharmacist
      shortage on medication errors. The paper examines past research regarding the
      impact of pharmacists on medication errors, as well as a recent unique survey
      that attempted to directly examine the impact of the shortage on medication
      errors. The paper finds a collection of suggestive anecdotal evidence indicating
      the pharmacist shortage is having a negative impact on medication errors. In
      addition, several suggestions are made for future research regarding the
      relationship between pharmacists, the health system, and medication errors.

PMID- 15171071
TI  - Introducing a conceptual information retrieval (IR) framework.
AB  - This is the third in the series of the articles on an application of the systems
      analytic approach to evaluation of information retrieval (IR). Previously
      terminological and evaluation problems associated with IR were identified, and it
      was proposed that the systems analytic approach can provide solutions to these
      problems. Here, after the general discussion of a systems approach, different
      attempts to introduce this approach into IR are presented and critiqued:
      modelling of IR, identifying boundaries of a system under evaluation, identifying
      variables under investigation; and creating evaluation frameworks. On the basis
      of the critique of this work, the authors present their proposal for a solution:
      first the IR components, their boundaries and relationships are identified, and
      then the two models of IR are introduced. One of the models addresses components
      of the IR process and relationships between them, the second one is the process
      model of IR.

PMID- 15171070
TI  - A review of e-learning practices for undergraduate medical education.
AB  - This paper describes the findings of a literature review conducted on the current
      usage, lessons, and limitations of e-learning for undergraduate medical education
      with an emphasis on synchronous delivery in the first 2 years. The review was
      conducted as part of an initiative to expand the UBC undergraduate medical
      program in British Columbia, Canada. The 50 e-learning articles included in the
      review described the deployment of various types of e-learning technology and
      content in different settings. The seven videoconferencing articles provided
      product information, health education examples, and innovative approaches. The
      six review articles provided general guidelines and trends on e-learning in
      undergraduate medical education in United States and Europe. Overall, while the
      literature is informative, there are few reported studies that address
      distributed synchronous learning in these undergraduate programs.

PMID- 15171072
TI  - A new look at information retrieval evaluation: proposal for solutions.
AB  - This is the fourth and the final in the series of the papers on an application of
      the systems analytic approach to evaluation of information retrieval (IR). In the
      previous papers terminological and evaluation problems associated with IR were
      identified and discussed, and it was proposed that the systems analytic approach
      could provide solutions to these problems. A review of existing systems analytic
      approaches in IR was given, and a conceptual framework and two models of IR were
      presented. This paper discusses how the proposed conceptual framework and the
      models can be used to improve terminology of IR, to analyze the relevance-based
      method of recall and precision, and to propose new approaches to evaluate
      relevance relationships and search engines. The proposed evaluation approaches
      are compared amongst each other and with the existing methods. The paper is
      concluded by a summary of the contributions of the research and an identification
      of the directions for a future research in IR evaluation.

PMID- 15171073
TI  - How to adjust ACE inhibitors and ARBs in diabetes?

PMID- 15171074
TI  - Acute infectious gastroenteritis in adults. Seven steps to management and
      prevention.
AB  - In caring for patients with acute gastroenteritis, the physician's primary task
      is to assess the severity of illness and to tailor fluid and electrolyte
      replacement and symptomatic therapy accordingly. Antibiotics are seldom indicated
      for acute gastroenteritis, and it is up to the physician to make a rational,
      informed choice about their use. Narrowing the considerations in differential
      diagnosis can help guide decision making about the need for diagnostic tests,
      specific therapy, and public health intervention.

PMID- 15171075
TI  - A lesion with lymphangitic spread in a gardener. Exposure to soil increases risk
      of sporotrichosis.

PMID- 15171076
TI  - Management of hypercalcemia. Diagnostic workup, therapeutic options for
      hyperparathyroidism and other common causes.
AB  - Hypercalcemia is a common metabolic condition encountered in both inpatient and
      outpatient settings. Physicians can more successfully diagnose and treat patients
      when armed with a thorough understanding of normal calcium metabolism and how it
      can be disrupted by disease. In virtually all cases, the cause of an elevated
      serum calcium concentration can be quickly ascertained through the use of
      selected diagnostic tests. Effective treatment options can then be implemented.

PMID- 15171077
TI  - Mild persistent asthma. Traits, treatment set it apart from mild intermittent
      asthma.
AB  - Mild persistent asthma has greater airway hyperresponsiveness than mild
      intermittent asthma and may also have more persistent respiratory symptoms and
      more severe consequences. By other measures, the two conditions are not always
      easy to differentiate. Nevertheless, primary care physicians need to be able to
      recognize and treat mild persistent asthma in order to reduce the number of
      severe exacerbations, and even fatalities, that can occur if it is not properly
      managed. In this article, Dr Lim discusses how to differentiate mild persistent
      asthma from mild intermittent asthma and explores the best options for
      pharmacologic treatment.

PMID- 15171078
TI  - Managing asthma during pregnancy. The whys and hows of aggressive control.
AB  - Asthma occurs in about 4% of pregnancies and can worsen during pregnancy.
      Aggressive treatment is needed because failure to control asthma during pregnancy
      can lead to poor outcomes for both mother and child. At the same time, the risk
      benefit profile of various asthma medications should be considered to avoid any
      adverse effects. In this article, Dr Blaiss discusses the foundations for
      management of asthma during pregnancy: environmental control, pharmacotherapy,
      and allergen immunotherapy.

PMID- 15171079
TI  - Does rhinitis lead to asthma? Evidence for the one-airway hypothesis.
AB  - The link between upper airway disease (allergic rhinitis) and lower airway
      disease (asthma) has long been of interest to physicians. Recently, extensive
      research has established that epidemiologic and therapeutic links exist between
      allergic rhinitis and asthma. Other recent evidence has provided a better
      understanding of the pathophysiologic interrelationship between allergic rhinitis
      and asthma. Such information has had an impact on the management of these
      disorders, including treatment and prophylaxis.

PMID- 15171080
TI  - Advances in liver transplantation. New strategies and current care expand access,
      enhance survival.
AB  - Liver transplantation revolutionized the management of liver disease. Although
      the number of patients who could benefit from a transplant far exceeds the number
      of available cadaveric donors, new strategies, such as splitting cadaveric organs
      and using living donors, have expanded access to transplantation. Here, a team of
      transplant physicians highlights these new strategies, as well as the long-term
      management issues of special relevance to primary care physicians caring for
      transplant recipients.

PMID- 15171081
TI  - A statin for a patient with hyperlipidemia and hepatitis C?

PMID- 15171082
TI  - Heeding clues to giant cell arteritis. Prompt response can prevent vision loss.
AB  - To return to the case vignette, the new onset of headache in a 74-year-old woman
      with anemia and a markedly elevated ESR should alert the physician to the strong
      possibility of giant cell arteritis. Vision loss is the most significant
      potential early complication. Temporal artery biopsy is indicated, and treatment
      with corticosteroids should be started immediately. Close monitoring of the
      patient's symptoms and laboratory parameters is critical, as is surveillance for
      potential late complications.

PMID- 15171083
TI  - Bilateral ear swelling and cough. Relapsing polychondritis.

PMID- 15171084
TI  - Patient notes: sunburn.

PMID- 15171089
TI  - Diabetes and physical activity in school.
AB  - Physical activity and exercise are critical components of diabetes management.
      Everyone can benefit from regular exercise, but it is even more important for a
      student with diabetes. In addition to maintaining cardiovascular fitness and
      controlling weight, physical activity can help to lower blood glucose levels and
      increase insulin sensitivity. With the nearly epidemic incidence of childhood
      obesity and type 2 diabetes in youth, physical education should be part of the
      school day for all children. Students with diabetes should participate fully in
      physical education classes and team sports. To maintain blood glucose levels
      within their target ranges during exercise, students with type 1 diabetes will
      make adjustments in their insulin and food intake. To prevent hypoglycemia, they
      also will need to check their blood glucose levels more frequently while engaging
      in physical activity. Physical education instructors and sports coaches must be
      able to recognize and assist with the treatment of hypoglycemia. A quick-acting
      source of glucose and the student's glucose meter should always be available,
      along with water. The student's Diabetes Medical Management Plan, nursing care
      plan, 504 Plan, IEP, or other education plan should include specific
      instructions.

PMID- 15171091
TI  - Bullying behavior and injuries in the elementary school setting. Is there a
      relationship?

PMID- 15171092
TI  - Safe play takes planning: what role would you have?

PMID- 15171094
TI  - Understanding teenage mothering: conventional and unconventional wisdom.

PMID- 15171093
TI  - Prevention: the best way to help our kids avoid the obesity epidemic.

PMID- 15171096
TI  - 'Stormy waters' ahead for Scots service reform.

PMID- 15171095
TI  - ACTIVATE: a childhood overweight prevention initiative.

PMID- 15171097
TI  - Clinical management. Where medicine meets management. Way to go.
AB  - When setting up an ICP, invite participation from all relevant healthcare
      professionals in both primary and secondary care. Gather all research and best
      practice using national guidelines or best available evidence. Consult patients:
      they often have knowledge unavailable to medical professionals.

PMID- 15171098
TI  - Nursing. Vision express.
AB  - Trusts that took part in a series of seminars last year are implementing ideas
      for a 'nurse-envisaged' NHS. Results have included new nurse consultant posts in
      Birmingham and ongoing nurse practitioner training in Northumbria. A Bradford PCT
      is introducing advanced primary care nurses in line with the Evercare model of
      care.

PMID- 15171099
TI  - Community engagement. Streets ahead.
AB  - A survey of NHS staff by the Commission for Health Improvement highlighted top
      performing PCTs on community engagement. Numbers attending public meetings can be
      boosted by targeting transport and using existing networks. A number of PCTs have
      helped community links by moving staff out of NHS locations.

PMID- 15171100
TI  - Finance. Hole in one.

PMID- 15171101
TI  - HSJ people. Support system.

PMID- 15171102
TI  - The contribution of daily experiences and acute exercise to fluctuations in daily
      feeling states among older, obese adults with knee osteoarthritis.
AB  - This study examined the contribution of daily experiences and acute exercise to
      fluctuations in feeling states of older, obese adults with knee osteoarthritis
      and explored the role of perceived physical function and general health
      perceptions as moderator variables. Using an experience sampling procedure, a
      total of 964 feeling state assessments were recorded and coded into samplings
      that occurred either on a nonexercise day or prior to or following scheduled
      activity on an exercise day. Multilevel modeling analyses controlling for the
      influence of subjective stress, contemporaneous pain reports, and diurnal
      variations revealed that physical exhaustion was higher immediately following
      exercise. Analyses of the moderator variables demonstrated that general health
      perceptions and perceived physical function accounted for significant portions of
      between-subject variance with more positive perceptions of each variable being
      related to higher levels of pleasant feeling states and lower feelings of
      physical exhaustion. However, perceived physical function and general health
      perceptions did not influence feeling states that emerged in conjunction with
      physical activity. The present findings suggest that whereas daily fluctuations
      in feeling states are influenced by perceived physical function and general
      health perceptions, older adults with knee OA do not exhibit the improvements in
      feeling states that have often been observed following acute exercise in younger,
      more physically active populations.

PMID- 15171103
TI  - Coping competence as predictor and moderator of depression among chronic disease
      patients.
AB  - This tested the utility of the "Coping Competence Questionnaire" (CCQ) in
      predicting depression among chronic disease patients. Coping competence is
      defined as a dispositional stress resistance factor based on helplessness and
      hopelessness theory. Predictive power and buffering effects of the CCQ were
      tested in three patient samples scheduled for Coronary Artery Bypass Surgery (N =
      272), other heart surgeries (N = 109), or lung tumor surgery (N = 203). Coping
      competence, symptom stress, and depression were assessed before and 6-months
      following surgery. Hierarchical multiple regressions indicated moderator effects
      of coping competence in the relationship between symptom stress and depression,
      supporting the stress-buffer hypothesis. Symptom stress was strongly correlated
      with depression among patients who were low in coping competence only. Among
      patients high in coping competence, depression was low and unaffected by symptom
      stress. The results suggest that the 12-item coping competence scale may qualify
      as useful tool for the prediction of depression in chronic disease populations.

PMID- 15171104
TI  - Personality characteristics as differential variables of the pain experience.
AB  - This study analyzes the relationships between neuroticism, extroversion, age, and
      sex and the intensity of perceived pain and the coping strategies used. We worked
      with a sample of 96 patients with chronic pain. The assessment tools were the
      following: the Vanderbilt Pain Management Inventory, a Spanish version of the
      McGill Pain Questionnaire, and the Eysenck Personality Inventory. The
      hypothetical model establishes positive relationships between neuroticism, the
      use of passive coping strategies, and the intensity of pain. On the other hand,
      extraversion is expected to be positively related to the use of active coping
      strategies and negatively related to the perceived intensity of pain. The results
      support the hypotheses formulated regarding the effects of the variables
      neuroticism and extraversion. Age is negatively related to active coping
      strategies and pain intensity. Men use more active strategies than women, while
      the latter have a greater perception of pain.

PMID- 15171105
TI  - Psychometric evaluation of the Pain Anxiety Symptoms Scale (PASS) in chronic pain
      patients.
AB  - This study examined psychometric properties of the Pain Anxiety Symptoms Scale
      (PASS), a measure of pain-related fear. A recently developed shortened version of
      the PASS, the PASS-20, was also investigated. Previously reported factor
      structures of the PASS were tested by means of confirmatory factor analysis.
      Results indicated that all models fitted adequately but that a five-factor
      solution fitted slightly better compared to the other models tested. The four
      factor solution of the PASS-20 was tested by means of confirmatory factor
      analysis and results indicated adequate fit. Moreover, the four-factor solution
      of the PASS-20 was invariant among fibromyalgia and low-back pain patients.
      Convergent validity of the original PASS and the PASS-20 was good and internal
      consistency reliability adequate to excellent. The suitability of the original
      PASS and the PASS-20 are discussed and directions for future research are
      provided.

PMID- 15171106
TI  - Appearance versus health: does the reason for dieting affect dieting behavior?
AB  - This study investigated whether dieting out of concern for one's health, as
      opposed to for appearance reasons, is associated with the same negative
      consequences normally associated with chronic dieting. One hundred student and 96
      community women dieters completed measures of various eating behaviors,
      psychological variables, and motivations behind their dieting. The findings
      indicated that individuals who were motivated to change their appearance through
      dieting were younger than those dieting to improve their health. They were also
      more likely to use drastic dieting strategies, and to score higher on measures of
      disinhibited eating, or lapses in restraint. On the other hand, dieting driven by
      health concerns was associated with fewer negative sequelae. These results
      suggest that not all dietary behavior labelled as "dieting" is equally harmful,
      and that the driving force behind the dieting is a more important factor to
      consider than dietary restrictions per se.

PMID- 15171107
TI  - Gail model risk assessment and risk perceptions.
AB  - Patients can benefit from accessible breast cancer risk information. The Gail
      model is a well-known means of providing risk information to patients and for
      guiding clinical decisions. Risk presentation often includes 5-year and life-time
      percent chances for a woman to develop breast cancer. How do women perceive their
      risks after Gail model risk assessment? This exploratory study used a randomized
      clinical trial design to address this question among women not previously
      selected for breast cancer risk. Results suggest a brief risk assessment
      intervention changes quantitative and comparative risk perceptions and improves
      accuracy. This study improves our understanding of risk perceptions by evaluating
      an intervention in a population not previously selected for high-risk status and
      measuring perceptions in a variety of formats.

PMID- 15171108
TI  - Who's the RN?

PMID- 15171109
TI  - Nurses against tobacco.

PMID- 15171111
TI  - Nursing's stories.

PMID- 15171112
TI  - Surviving cancer.

PMID- 15171110
TI  - Breast cancer awareness.

PMID- 15171113
TI  - Anticoagulant-induced skin necrosis.

PMID- 15171114
TI  - Image, function, and style. A history of the nursing uniform.

PMID- 15171115
TI  - Emergency. Tumor lysis syndrome.

PMID- 15171116
TI  - Ethics and palliative care in pediatrics.

PMID- 15171117
TI  - Born into a diaper.

PMID- 15171118
TI  - Medicare's preventive services.

PMID- 15171119
TI  - Building a network of nurse experts.

PMID- 15171120
TI  - A needling problem.

PMID- 15171121
TI  - Counseling to prevent skin cancer: recommendations and rationale.

PMID- 15171122
TI  - The precautionary approach.

PMID- 15171123
TI  - Modal damping for monitoring bone integrity and osteoporosis.
AB  - We applied a noninvasive method to assess bone structural integrity. The method
      is based on the measurement of the dynamic characteristics of the bone (quality
      factor and modal damping factor) by applying vibration excitation in the range of
      acoustic frequencies, in the form of an acoustic sweep signal. Excised sheep
      femora were tested to detect changes in modal damping, density (kg/m3), bone
      mineral density (kg/m2) and bone mineral (hydroxyapatite) percentage. The changes
      were recorded after each time of chemical treatment of the bones performed to
      gradually cause mineral removal, thus simulating osteoporosis. It was shown that
      the change in quality factor and damping was in all cases on average equal or
      greater to the change in all other measured characteristics, thus strengthening
      the potential of the proposed method to become a valuable assessment tool for
      monitoring bone integrity and osteoporosis.

PMID- 15171124
TI  - The influence of the fixed negative charges on mechanical and electrical
      behaviors of articular cartilage under unconfined compression.
AB  - Unconfined compression test has been frequently used to study the mechanical
      behaviors of articular cartilage, both theoretically and experimentally. It has
      also been used in explant and gel-cell-complex studies in tissue engineering. In
      biphasic and poroelastic theories, the effect of charges fixed on the
      proteoglycan macromolecules in articular cartilage is embodied in the apparent
      compressive Young's modulus and the apparent Poisson's ratio of the tissue, and
      the fluid pressure is considered to be the portion above the osmotic pressure. In
      order to understand how proteoglycan fixed charges might affect the mechanical
      behaviors of articular cartilage, and in order to predict the osmotic pressure
      and electric fields inside the tissue in this experimental configuration, it is
      necessary to use a model that explicitly takes into account the charged nature of
      the tissue and the flow of ions within its porous interstices. In this paper, we
      used a finite element model based on the triphasic theory to study how fixed
      charges in the porous-permeable soft tissue can modulate its mechanical and
      electrochemical responses under a step displacement in unconfined compression.
      The results from finite element calculations showed that: 1) A charged tissue
      always supports a larger load than an uncharged tissue of the same intrinsic
      elastic moduli. 2) The apparent Young's modulus (the ratio of the equilibrium
      axial stress to the axial strain) is always greater than the intrinsic Young's
      modulus of an uncharged tissue. 3) The apparent Poisson's ratio (the negative
      ratio of the lateral strain to the axial strain) is always larger than the
      intrinsic Poisson's ratio of an uncharged tissue. 4) Load support derives from
      three sources: intrinsic matrix stiffness, hydraulic pressure and osmotic
      pressure. Under the unconfined compression, the Donnan osmotic pressure can
      constitute between 13%-22% of the total load support at equilibrium. 5) During
      the stress-relaxation process following the initial instant of loading, the
      diffusion potential (due to the gradient of the fixed charge density and the
      associated gradient of ion concentrations) and the streaming potential (due to
      fluid convection) compete against each other. Within the physiological range of
      material parameters, the polarity of the electric potential depends on both the
      mechanical properties and the fixed charge density (FCD) of the tissue. For
      softer tissues, the diffusion effects dominate the electromechanical response,
      while for stiffer tissues, the streaming potential dominates this response. 6)
      Fixed charges do not affect the instantaneous strain field relative to the
      initial equilibrium state. However, there is a sudden increase in the fluid
      pressure above the initial equilibrium osmotic pressure. These new findings are
      relevant and necessary for the understanding of cartilage mechanics, cartilage
      biosynthesis, electromechanical signal transduction by chondrocytes, and tissue
      engineering.

PMID- 15171125
TI  - Modes and balance of energy in the piezoelectric cochlear outer hair cell wall.
AB  - Here, we analyze energy transformations in the outer hair cell and its
      effectiveness as a piezoelectric-type actuator in the cochlea. The major modes of
      energy are introduced, and a method to estimate the coefficients of their tension
      dependence is proposed. Next, we derive balance of the mechanical and electrical
      parts of energy, and show two forms of the active energy associated with the
      motors driving electromotility. The two forms of the active energy, stored
      mechanical energy, and external electrical work are then introduced as functions
      of voltage and applied force. We use the energy balance to introduce and estimate
      the effectiveness of the cell's electromotile response.

PMID- 15171126
TI  - An in vivo method for measuring turbulence in mechanical prosthesis leakage jets.
AB  - This work introduces a method for the in vivo measurement and analysis of
      turbulence within the leakage of a mechanical heart valve. Several analysis
      techniques were applied to ultrasound measurements acquired within the atrium of
      a pig, and error associated with these techniques was analyzed. The technique
      chosen applies cyclic averaging to mean and maximum velocity measurements within
      small, normalized phase windows to calculate Reynolds normal stresses in the
      direction of the ultrasound beam. Maximum shear stresses are estimated from these
      normal stresses using an analytical technique. The stresses observed were smaller
      than those reported from previous in vitro simulations.

PMID- 15171127
TI  - Intra-aneurysmal flow with helix and mesh stent placement across side-wall
      aneurysm pore of a straight parent vessel.
AB  - Pulsatile flow fields in a cerebrovascular side-wall aneurysm model with a wide
      ostium after stenting are presented in terms of particle tracking velocimetry
      measurements and flow visualization. Among the stent parameters the shape, helix
      versus mesh, was selected to study its effect on the changes of intraaneurysmal
      hemodynamics for the reference of minimally invasive endovascular aneurysm
      treatment. The blocking ratio of the stents was fixed at 30%. The Womersley
      number was 3.9 and the mean, peak, and minimal Reynolds numbers based on the bulk
      average velocity and diameter of the parent vessel were 600, 850, and 300,
      respectively. Four consecutive flow-rate phases were selected to characterize the
      intra-aneurysmal flow. The results are characterized in terms of velocity vector
      field, regional average velocity, and intra-aneurysmal vorticity/circulation/wall
      shear stress. It is found that the hemodynamic features inside the aneurysm alter
      markedly with the shape of the stent and the size of the orifice. Both stents
      investigated induce favorable changes in the intra-aneurysmal flow stasis as well
      as direction and undulation of wall shear stresses. A comparison of the results
      of the helix to mesh stent shows that the former is more favorable for
      endovascular treatment.

PMID- 15171128
TI  - 3-D anatomically based dynamic modeling of the human knee to include tibio
      femoral and patello-femoral joints.
AB  - An anatomical dynamic model consisting of three body segments, femur, tibia and
      patella, has been developed in order to determine the three-dimensional dynamic
      response of the human knee. Deformable contact was allowed at all articular
      surfaces, which were mathematically represented using Coons' bicubic surface
      patches. Nonlinear elastic springs were used to model all ligamentous structures.
      Two joint coordinate systems were employed to describe the six-degrees-of-freedom
      tibio-femoral (TF) and patello-femoral (PF) joint motions using twelve kinematic
      parameters. Two versions of the model were developed to account for wrapping and
      nonwrapping of the quadriceps tendon around the femur. Model equations consist of
      twelve nonlinear second-order ordinary differential equations coupled with
      nonlinear algebraic constraint equations resulting in a Differential-Algebraic
      Equations (DAE) system that was solved using the Differential/Algebraic System
      Solver (DASSL) developed at Lawrence Livermore National Laboratory. Model
      calculations were performed to simulate the knee extension exercise by applying
      non-linear forcing functions to the quadriceps tendon. Under the conditions
      tested, both "screw home mechanism" and patellar flexion lagging were predicted.
      Throughout the entire range of motion, the medial component of the TF contact
      force was found to be larger than the lateral one while the lateral component of
      the PF contact force was found to be larger than the medial one. The anterior and
      posterior fibers of both anterior and posterior cruciate ligaments, ACL and PCL,
      respectively, had opposite force patterns: the posterior fibers were most taut at
      full extension while the anterior fibers were most taut near 90 degrees of
      flexion. The ACL was found to carry a larger total force than the PCL at full
      extension, while the PCL carried a larger total force than the ACL in the range
      of 75 degrees to 90 degrees of flexion.

PMID- 15171129
TI  - A novel robotic system for joint biomechanical tests: application to the human
      knee joint.
AB  - The objectives of the work reported in this article were to develop a novel 6
      degree-of-freedom (DOC) robotic system for knee joint biomechanics, to complete a
      hybrid force-position control scheme, to evaluate the system performance, and to
      demonstrate a combined loading test. The manipulator of the system utilizes two
      mechanisms; the upper mechanism has two translational axes and three rotational
      axes while the lower mechanism has only a single translational axis. All axes
      were driven with AC servo-motors. This unique configuration results in a simple
      kinematic description of manipulator motion. Jacobian transformation was used to
      calculate both the displacement and force/moment, which allowed for a hybrid
      control of the displacement of, and force/moment applied to, the human knee
      joint. The control and data acquisition were performed on a personal computer in
      the C-language programming environment with a multi-tasking operating system.
      Preliminary tests revealed that the clamp-to-clamp compliance of the system was
      smaller in the vertical (Z) and longitudinal (Y) directions (0.001 mm/N) than in
      lateral (X) direction (0.003 mm/N). The displacement error under the application
      of 500 N of load was smallest in the vertical direction (0.001 +/- 0.003 mm (mean
      +/- SD), and largest in the lateral direction (0.084 +/- 0.027 mm). Using this
      test system, it was possible to simulate multiple loading conditions in a human
      knee joint in which a cyclic anterior force was applied together with a coupled,
      joint compressive force, while allowing natural knee motion. The developed system
      seems to be a useful tool for studies of knee joint biomechanics.

PMID- 15171130
TI  - How cyclic loading affects the migration of radio-opaque markers attached to
      tendon grafts using a new method: a study using roentgen stereophotogrammetric
      analysis (RSA).
AB  - An increase in anterior laxity following reconstruction of the anterior cruciate
      ligament (ACL) can result from lengthening of the graft construct in either the
      regions of fixation and/or the region of the graft substance between the
      fixations. RSA could be a useful technique to determine lengthening in these
      regions if a method can be devised for attaching radio-opaque markers to soft
      tissue grafts so that marker migration from repeated loading of the graft is
      limited. Therefore, the objectives of this study were 1) to develop a method for
      attaching radio-opaque markers to an ACL graft that limits marker migration
      within the graft, 2) to characterize the error of an RSA system used to study
      migration, and 3) to determine the maximum amount of migration and the time when
      it occurs during cyclic loading of ACL grafts. Tendon markers were constructed
      from a 0.8-mm tantalum ball and a stainless steel suture. Ten double-looped
      tendon grafts were passed through tibial tunnels drilled in bovine tibias and
      fixed with a tibial fixation device. Two tendon markers were sewn to one tendon
      bundle of each graft and the grafts were cyclically loaded for 225,000 cycles
      from 20 N to 170 N. At specified intervals, simultaneous radiographs were
      obtained of the tendon markers and a radiographic standard of known length. The
      bias and imprecision in measuring the length of the radiographic standard were
      0.0 and 0.046 mm respectively. Marker migration was computed as the change in
      distance between the two tendon markers along the axis of the tibial tunnel.
      Marker migration was greatest after 225,000 cycles with a root mean square (RMS)
      value of less than 0.2 mm. Because the RMS value indicates the error introduced
      into measurements of lengthening and because this error is small, the method
      described for attaching markers to an ACL graft has the potential to be useful
      for determining lengthening of ACL graft constructs in in vivo studies in humans.

PMID- 15171131
TI  - Effects of ischemia on epicardial deformation in the passive rabbit heart.
AB  - BACKGROUND: Surgically induced ischemia in the arrested heart can result in
      changes in the mechanical properties of the myocardium. Regions of ischemia may
      be characterized based on the amount of epicardial deformation for a given load.
      Computer aided speckle interferometry (CASI), which tracks the movement of
      clusters of particles, is developed as a technique for measuring epicardial
      deformation, thereby determining the perfusion status of the passive heart.
      MATERIALS AND METHODS: Silicone carbide particles and retroreflective beads were
      dispersed randomly onto the epicardial surface of 11 isolated rabbit hearts to
      form speckle images. The hearts were arrested with hyperkalemic Krebs-Henseleit
      buffered solution. Each heart was then exposed to a series of intracavitary
      pressures, and at each pressure speckle images were acquired with a charge
      coupled device (CCD) camera. Nine hearts were exposed to global ischemia, and two
      hearts were exposed to regional ischemia by occluding the second diagonal branch
      of the left anterior descending artery (LAD). The hearts were again loaded and
      the speckle images were acquired. CASI was used to determine the distribution of
      deformation field. RESULTS: CASI was able to determine displacements with a
      spatial resolution of about 50 microns. Global ischemia resulted in a significant
      increase in the maximum principle strain and the first invariant of the 2-D
      strain tensor. In the regionally ischemic heart, a large difference in
      deformation between the ischemic and perfused regions was clearly observed.
      CONCLUSION: Based on epicardial deformation, CASI is able to distinguish between
      perfused and ischemic myocardium, with a spatial resolution of 50 microns.

PMID- 15171132
TI  - Mechanical properties of rat middle cerebral arteries with and without myogenic
      tone.
AB  - The inner diameter and wall thickness of rat middle cerebral arteries (MCAs) were
      measured in vitro in both a pressure-induced, myogenically-active state and a
      drug-induced, passive state to quantify active and passive mechanical behavior.
      Elasticity parameters from the literature (stiffness derived from an exponential
      pressure-diameter relationship, beta, and elasticity in response to an increment
      in pressure, Einc-p) and a novel elasticity parameter in response to smooth
      muscle cell (SMC) activation, Einc-a, were calculated. beta for all passive MCAs
      was 9.11 +/- 1.07 but could not be calculated for active vessels. The incremental
      stiffness increased significantly with pressure in passive vessels; Einc-p (10(6)
      dynes/cm2) increased from 5.6 +/- 0.5 at 75 mmHg to 14.7 +/- 2.4 at 125 mmHg, (p
      < 0.05). In active vessels, Einc-p (10(6) dynes/cm2) remained relatively constant
      (5.5 +/- 2.4 at 75 mmHg and 6.2 +/- 1.0 at 125 mmHg). Einc-a (10(6) dynes/cm2)
      increased significantly with pressure (from 15.1 +/- 2.3 at 75 mmHg to 49.4 +/-
      12.6 at 125 mmHg, p < 0.001), indicating a greater contribution of SMC activity
      to vessel wall stiffness at higher pressures.

PMID- 15171133
TI  - An integrated finite-element approach to mechanics, transport and biosynthesis in
      tissue engineering.
AB  - A finite-element approach was formulated, aimed at enabling an integrated study
      of mechanical and biochemical factors that control the functional development of
      tissue engineered constructs. A nonlinear biphasic displacement-velocity-pressure
      description was combined with adjective and diffusive solute transport, uptake
      and biosynthesis. To illustrate the approach we focused on the synthesis and
      transport of macromolecules under influence of fluid flow induced by cyclic
      compression. In order to produce net transport the effect of dispersion was
      investigated. An abstract representation of biosynthesis was employed, three
      cases were distinguished: Synthesis dependent on a limited small solute,
      synthesis dependent on a limited large solute and synthesis independent of solute
      transport. Results show that a dispersion model can account for augmented solute
      transport by cyclic compression and indicate the different sensitivity to loading
      that can be expected depending on the size of the limiting solute.

PMID- 15171134
TI  - An improved method to analyze the stress relaxation of ligaments following a
      finite ramp time based on the quasi-linear viscoelastic theory.
AB  - The quasi-linear viscoelastic (QLV) theory proposed by Fung (1972) has been
      frequently used to model the nonlinear time- and history-dependent viscoelastic
      behavior of many soft tissues. It is common to use five constants to describe the
      instantaneous elastic response (constants A and B) and reduced relaxation
      function (constants C, tau 1, and tau 2) on experiments with finite ramp times
      followed by stress relaxation to equilibrium. However, a limitation is that the
      theory is based on a step change in strain which is not possible to perform
      experimentally. Accounting for this limitation may result in regression
      algorithms that converge poorly and yield nonunique solutions with highly
      variable constants, especially for long ramp times (Kwan et al. 1993). The goal
      of the present study was to introduce an improved approach to obtain the
      constants for QLV theory that converges to a unique solution with minimal
      variability. Six goat femur-medial collateral ligament-tibia complexes were
      subjected to a uniaxial tension test (ramp time of 18.4 s) followed by one hour
      of stress relaxation. The convoluted QLV constitutive equation was simultaneously
      curve-fit to the ramping and relaxation portions of the data (r2 > 0.99).
      Confidence intervals of the constants were generated from a bootstrapping
      analysis and revealed that constants were distributed within 1% of their median
      values. For validation, the determined constants were used to predict peak
      stresses from a separate cyclic stress relaxation test with averaged errors
      across all specimens measuring less than 6.3 +/- 6.0% of the experimental values.
      For comparison, an analysis that assumed an instantaneous ramp time was also
      performed and the constants obtained for the two approaches were compared.
      Significant differences were observed for constants B, C, tau 1, and tau 2, with
      tau 1 differing by an order of magnitude. By taking into account the ramping
      phase of the experiment, the approach allows for viscoelastic properties to be
      determined independent of the strain rate applied. Thus, the results obtained
      from different laboratories and from different tissues may be compared.

PMID- 15171135
TI  - Determinants of left ventricular shape change during filling.
AB  - Left ventricular shape and shape change are easy to measure and their analysis
      has been proposed as a noninvasive method to determine myocardial anisotropy. In
      preparation for applying this approach to studies of rats with experimentally
      induced cardiac hypertrophy, the goals of this study were to describe normal
      shape changes during diastolic filling in the rat and to utilize a finite-element
      model to estimate the relative importance of three factors that determine left
      ventricular shape change during filling: global chamber compliance, fiber to
      crossfiber stiffness ratio, and fiber architecture. The results suggest that left
      ventricular shape change is least sensitive to fiber to cross fiber stiffness
      ratio, and that this will likely limit the practical utility of using shape
      changes to diagnose changes in myocardial anisotropy.

PMID- 15171136
TI  - Mechanical properties of a reversible, DNA-crosslinked polyacrylamide hydrogel.
AB  - Mechanical properties of a polyacrylamide gel with reversible DNA crosslinks are
      presented. In this system, three DNA strands replace traditional chemical
      crosslinkers. In contrast to thermoset chemically crosslinked polyacrylamide, the
      new hydrogel is thermoreversible; crosslink dissociation without the addition of
      heat is also feasible by introducing a specific removal DNA strand. This hydrogel
      is characterized by a critical crosslink concentration at which gelation occurs.
      Below the critical point, a characteristic temperature exists at which a
      transition in viscosity is observed. Both temperature-dependent viscosity and
      elastic modulus of the material are functions of crosslink density.

PMID- 15171137
TI  - Experimental and numerical modeling of variable friction between nanoregions in
      coventional and crosslinked UHMWPE.
AB  - Recently, highly crosslinked UHMWPE components have been promoted for their high
      abrasive wear resistance over conventional UHMWPE (PE) in total joint replacement
      (TJR) prostheses to minimize osteolysis and consequent implant loosening. This
      study was aimed at investigating the role of friction gradients induced by
      localized coefficients of friction at both crystalline and amorphous nanoregions
      in PE, and crystalline and crosslinked nanoregions in crosslinked UHMWPE (XPE),
      in submicron wear debris generation. An abrasive wear study performed on both XPE
      and PE using atomic force microscopy (AFM) illustrated that the onset of plastic
      deformation for XPE occurred at a normal load that was approximately 3 times
      higher when compared to PE. Coefficients of friction (mu d) of 0.2, 0.35, and
      0.61, experimentally derived using AFM, were used as representative mu d for
      crystalline, amorphous, and crosslinked nanoregions, respectively, in a numerical
      Hertzian model. An increase in mu (0.2 +/- 0.02, 0.35 +/- 0.01 and 0.6 +/- 0.04)
      was observed with a decrease in crystallinity and storage modulus at 22 degrees
      C. Using the Hertzian contact model, it was observed that variability in friction
      between nanoregions contributed to higher magnitude stresses for XPE (0.2 to
      0.61; maximum sigma eff = 2.8) compared to PE (0.2 to 0.35; maximum sigma eff =
      1.1) over a negligible thickness of the interfacial zone (IZ) between
      nanoregions. The experimentally observed increase in abrasive wear resistance of
      XPE could be attributed to an increase in the thickness of the interfacial zone
      between nanoregions with mu changing gradually from crystalline to crosslinked
      nanoregions, a situation that may not be observed with PE. This would cause a
      decrease in the friction gradient and resulting stresses thereby agreeing with
      the observed experimental higher abrasive wear resistance for XPE. However, in
      both PE and XPE, the presence of stress concentrations over a period of time
      could lead to irreversible damage of the material eventually generating submicron
      wear debris. Hence, semicrystalline, inhomogenous UHMWPE with several nanoregions
      (amorphous and crystalline) would be at a disadvantage for bearing application in
      terms of abrasive wear resistance compared to UHMWPE with relatively lower number
      of nanoregions and crosslinked nanoregions.

PMID- 15171138
TI  - Mechanical properties of shock-absorbing pylons used in transtibial prostheses.
AB  - Prosthetic manufacturers have developed shock-absorbing pylons to attenuate the
      transient forces of foot-ground contact in order to supplement the residual
      capacity of lower limb amputees. The purpose of this study was to measure the
      elastic and damping properties of two frequently prescribed pylons (the ICON
      Shock Pylon and the Mercury TT Pyramid Pylon) at frequencies enveloping those
      observed during gait using pseudo-static compressive and dynamic cyclic testing
      methods. Results showed that the spring constants were linear functions of
      deformation (ranging from 74 to 110 N/mm and 91 to 157 N/mm for the ICON and the
      TT Pylons, respectively) while the damping force was a function of the square
      root of velocity combined with a coulomb element (1.6x0.5 + 21 and 7.4x0.5 + 102
      N for the ICON and the TT Pylon, respectively).

PMID- 15171140
TI  - Who's standards, anyway?

PMID- 15171139
TI  - Preparation of on-axis cylindrical trabecular bone specimens using micro-CT
      imaging.
AB  - The Orientation of trabecular bone specimens for mechanical testing must be
      carefully controlled. A method for accurately preparing on-axis cylindrical
      specimens using high-resolution micro-CT imaging was developed. Sixteen
      cylindrical specimens were prepared from eight bovine tibiae. High-resolution
      finite element models were generated from micro-CT images of parallelepipeds and
      used to determine the principal material coordinate system of each
      parallelepiped. A cylindrical specimen was then machined with a diamond coring
      bit. The resulting specimens were scanned again to evaluate the orientation. The
      average deviation between the principal fabric orientation and the longitudinal
      axis of the cylindrical specimen was only 4.70 +/- 3.11 degrees.

PMID- 15171141
TI  - Dealing with jury duty requests.

PMID- 15171142
TI  - Can I balance-bill fees denied by a no-fault insurer?

PMID- 15171143
TI  - Why do I need life insurance?

PMID- 15171145
TI  - How to lose an associate in 10 days.

PMID- 15171144
TI  - "Sip all day, get decay".

PMID- 15171146
TI  - NERB's transformation.

PMID- 15171147
TI  - Your MDA: safeguarding member value, preparing for the future.

PMID- 15171148
TI  - Funding for university nursing programs essential for public health.

PMID- 15171150
TI  - To mark International Women's Day. The OIIQ issues a position statement on
      screening for domestic abuse.

PMID- 15171149
TI  - A situation that has gone on too long. The OIIQ suggests solutions to support
      nurses practising in isolated regions.

PMID- 15171151
TI  - We're worried about the shortage of places in university nursing programs....

PMID- 15171152
TI  - Young nurses are worried. A shortage of places predicted in university nursing
      programs.

PMID- 15171153
TI  - A nurse's ethical obligations toward candidates for the practice of the
      profession and nursing externs.

PMID- 15171154
TI  - The impact of Daubert: implications for testimony and research in forensic
      anthropology (and the use of frontal sinuses in personal identification).
AB  - This paper emphasizes the need for objectivity and standardized methodologies in
      the forensic sciences, particularly physical anthropology. To this end, a review
      of important events in scientific evidence admissibility law, particularly the
      standards set in the case of Daubert v. Merrell-Dow Pharmaceuticals, Inc., 1993,
      is presented. The method of confirming a putative identification by visual
      comparison of antemortem and postmortem frontal sinus radiographs is examined in
      light of current admissibility standards. The technique is revealed to have a
      number of shortcomings, including a lack of empirical testing, no estimates of
      potential error rates, no standards controlling the technique's operation, and no
      objective determination standards. These shortcomings may, in some instances,
      prevent resulting conclusions from being admissible evidence. It is suggested
      that some methods (including frontal sinus comparison) may require more rigorous
      testing in order to meet these new and stricter standards.

PMID- 15171155
TI  - Identification of traumatic injury in burned cranial bone: an experimental
      approach.
AB  - Interpreting patterns of injury in victims of fire-related deaths poses
      challenges for forensic investigators. Determining manner of death (accident,
      suicide or homicide) using charred remains is compounded by the thermal
      distortion and fragmentation of soft and skeletal tissues. Heat degrades thin
      cranial structures and obscures the characteristic signatures of perimortem
      ballistic, blunt, and sharp force trauma in bone, making differentiation from
      thermal trauma difficult. This study documents the survivability and features of
      traumatic injury through all stages of burning for soft tissue reduction and
      organic degradation of cranial bone. Forty cadaver heads were burned in
      environments simulating forensic fires. Progression of thermal degradation was
      photographically documented throughout the destructive stages for soft tissues
      and bone to establish expected burn sequence patterns for the head. In addition
      to testing intact vaults, a percentage were selectively traumatized to introduce
      the variables of soft tissue disruption, fractures, impact marks, and incisions
      throughout the cremation process. Skeletal materials were recovered,
      reconstructed, and correlated with photographs to discern burn patterns and
      survivability of traumatic features. This study produced two important results:
      (1) Identification of preexistent trauma is possible in reconstructed burned
      cranial bone. Signatures of ballistic (internal and external bevel, secondary
      fractures), blunt force (impact site, radiating fractures), and sharp force
      (incisions, stabs, sectioning) survive the cremation process. (2) In non
      traumatized specimens, the skull does not explode from steam pressure but does
      fragment as a result of external forces (collapsed debris, extinguishment
      methods) and handling. The features of both results are sequentially described
      throughout the progression of thermal destruction.

PMID- 15171156
TI  - Comparison of age estimated from degree of racemization of aspartic acid,
      glutamic acid and alanine in the femur.
AB  - Aspartic acid (Asp) is generally used for estimation of age by measuring the
      degree of racemization. For other amino acids, however, there are few reports
      regarding the usefulness of the degree of racemization for the estimation of age.
      Accordingly, in this study using the femur (obtained from 21 cadavers) as the
      specimen, we measured the degree of racemization of glutamic acid (Glu) and
      alanine (Ala) along with Asp in the total amino acid (TAA) fraction as well as in
      acid-insoluble collagen-rich (IC) and acid-soluble peptide (SP) sub-fractions. We
      compared the degrees of racemization of each amino acid and the accuracy of the
      ages estimated from them. The degree of racemization and the reaction rate of
      racemization were ranked in the order of Asp > Glu > Ala in the TAA and IC
      fractions, but Asp > Ala > Glu in the SP fraction. It is noteworthy that the
      degrees of racemization differed between the three amino acids depending on the
      fraction tested. The correlation coefficient (r) between the degree of
      racemization and the chronological age was higher in the SP than in the TAA or IC
      fraction. Among three amino acids, Asp showed the highest correlation coefficient
      as predicted. The present study confirmed that Asp from the SP fraction is the
      best indicator for age estimation using racemization rates.

PMID- 15171158
TI  - A new technique for three-dimensional ultrasound scanning of facial tissues.
AB  - We report the development of an ultrasonic facial scanning technique that allows
      for the visualization of continuous contours without deforming surface tissues.
      Adhesive markers are placed on the face to enable measurement of facial tissue
      thicknesses at specific landmarks. The subject immerses the face in a clear
      plastic box filled with water for about 20 seconds while the researcher moves the
      transducer along the bottom of the box, guiding transducer movement by watching
      the facial image in a mirror placed below. 3D Echotech software (1) builds the
      images from sequentially acquired 2D frames. Reliability of repeat measurements
      at landmarks is good, and individual tissues (skin, subcutaneous, muscle) can be
      distinguished. The method is simple, reliable, less expensive and less time
      consuming than alternatives such as magnetic resonance imaging (MRI). It is
      applicable in both research and clinical contexts.

PMID- 15171157
TI  - Sexual dimorphism of the calcaneus of South African blacks.
AB  - Forensic anthropology is a rapidly growing field in South Africa and skeletal
      biologists are often called upon by the police to assist in personal
      identification from skeletal remains, which are recovered in suspected cases of
      homicide and suicide and in mass disaster. Measurements of the calcaneus have
      been shown to be sexually dimorphic in South African whites. Since the validity
      of discriminant function equations in sex determination is population specific,
      the aim of the present study was to derive similar equations for the calcanei of
      the South African blacks. The bones that were used in this study were obtained
      from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical
      Sciences, University of the Witwatersrand, Johannesburg. One hundred and sixteen
      (116) intact and non-pathological calcanei, consisting of 58 males and 58 females
      and belonging to individuals whose age at death ranged between 22 and 75 years,
      were selected by the simple random sampling technique. The measured variables
      included the maximum length, the load arm length, the dorsal articular facet
      length, the body height, the maximum height, the cuboidal facet height, the
      middle breadth, the dorsal articular facet breadth and the maximum breadth.
      Discriminant function analyses were done using the Statistical Product and
      Service Solutions (SPSS) program. All measured parameters of the calcaneus showed
      significant sexual differences. Length measurements were found to be the most
      sexually dimorphic. Combinations of variables provided better estimate of sex
      (79%-86%) than individual variables (64%-79%).

PMID- 15171159
TI  - Sex differences and aging of the vertebral column.
AB  - Morphological changes in the adult human skeleton have been recognized as useful
      for estimating the age at death. In the vertebral column, the development of
      osteophytes has been shown to be a general indicator of age, although substantial
      variation has been documented. The technique used for estimating age from
      osteophyte development is based exclusively on males and it is unknown whether
      patterns of osteophyte development are comparable between the sexes. This study
      examines sex differences in osteophyte development in the thoracic and lumbar
      regions of 384 individuals from the Terry Collection. Males and females in this
      sample show remarkably similar patterns of age-related changes in osteophyte
      development; however, females show greater variability in osteophyte stage for a
      given age. This was confirmed with age-matching a subsample of 128 individuals.
      Therefore, slightly larger confidence intervals should be used when assessing age
      from the vertebral column in females.

PMID- 15171161
TI  - Visualization and LC/MS analysis of colorless pepper sprays.
AB  - Pepper sprays are used in a variety of circumstances, including criminal
      activity, self-defense, and law enforcement. As such, the presence or absence of
      pepper sprays on evidentiary materials is often important when determining the
      facts of an incident. When no visible stains are present on evidentiary
      materials, ascertaining the presence or absence of pepper spray can be a
      challenge to the forensic analyst. A method, based on a chemical derivatization
      of capsaicinoids using a diazonium salt, has been developed for the visualization
      of colorless, ultraviolet (UV) activated fluorescent dye-free pepper sprays on
      textiles. Identification of both the capsaicinoids and their derivatives is
      confirmed via extraction of the derivatized capsaicinoids followed by liquid
      chromatography/mass spectrometry (LC/MS) analysis. LC/MS analysis is conducted
      using a YMC Basic column and elution of the compounds using a gradient of 10 mM
      ammonium formate, pH 4.2 and methanol at 0.35 mL/min. Full-scan MS data are
      collected for the full 6.5 min LC analysis. Although this method is qualitative
      in nature, visual detection of as little as 50 microL of a 0.2% pepper spray
      (equivalent to approximately 0.1 mg) on a variety of garments is possible, and
      more than adequate signal-to-noise is obtained for reconstructed ion
      chromatograms on LC/MS analysis at these levels.

PMID- 15171160
TI  - Anthropological data in individualization of skeletal remains from a forensic
      context in Kosovo--a case history.
AB  - There are many reports relating to victims and mass graves in the former
      Yugoslavia. They emphasize the importance of creating local skeletal
      identification standards. In this paper we deal with the first mass grave
      examined since the Kosovo crisis started and discuss problems regarding the
      identification process, especially the coincidence of antemortem with postmortem
      data. Twelve persons out of 39 bodies were identified using interviews with
      relatives and correspondence of biological data with personal effects and/or
      documents. Previous pathology was of crucial importance in the identification of
      three persons.

PMID- 15171162
TI  - Establishing the rDNA IGS structure of Cannabis sativa.
AB  - The rDNA intergenic spacer (IGS) structure of Cannabis sativa was established and
      can be used for classification and identification of this species. In this study,
      DNA fragments of rDNA IGS were amplified by PCR from Cannabis sativa plant
      extracts and a 1387 bp fragment was obtained. DNA sequence analysis revealed six
      different repeat motifs. In the middle of the IGS sequence, there were three
      sequence motifs, and the same three sections of DNA were then repeated with minor
      variation in sequence. The terminal region of the IGS was composed of another
      three different repeat units; multiple copies of these terminal repeat motifs
      were present in no discernible order. Within six repeat motifs, point variations
      were observed in five. The DNA sequence of the locus was compared with all the
      plant sequences registered in GenBank by the Fasta program of GCG software with
      the result that this DNA fragment was significantly different from any other DNA
      sequence recorded to date. The most similar sequence was that of Hops (Humulus
      lupulus), but with a similarity of only 88.9% over 579 bp. These specific and
      complex variations of IGS may be related to the species and geographic
      distributions.

PMID- 15171163
TI  - Using STR analysis to detect human DNA from exploded pipe bomb devices.
AB  - This study investigated the possibility of recovering a bomb assembler's DNA from
      an exploded pipe bomb device. Metal and polyvinyl chloride (PVC) pipes were
      examined to determine if one surface type would allow better DNA recovery than
      the other. Ten subjects each handled components of one metal and one PVC pipe
      bomb. The bombs were exploded, the fragments were collected and swabbed using the
      double swab technique, and the samples were extracted, quantified, amplified, and
      genotyped using polymerase chain reaction/short tandem repeat (PCR/STR). Of the
      20 bombs handled by the subjects, four bombs gave reportable results that matched
      the subject's known DNA profiles. An additional eight profiles, also matching the
      subject's known DNA profiles, were generated but were below the reportable
      threshold. There was no difference in the success rate of obtaining DNA profiles
      related to the use of either PVC or metal in the manufacture of the pipe bomb.
      The variables that appeared to have the greatest influence on the success of
      generating a DNA profile were the amount of fragmentation and subsequent recovery
      of the bomb fragments. It is suspected that successful DNA profiling could also
      be dependent upon the bomb assembler's propensity to slough skin cells on objects
      they handled.

PMID- 15171164
TI  - Development of a simulation model to assess the impact of contamination in
      casework using STRs.
AB  - Because contamination is usually tube-specific, negative controls cannot give
      assurance that an associated batch of extracted casework material is contaminant
      free. However, it is possible to use them to predict the level of overall
      (undetected) contamination that is processed by an operational DNA unit. A MATLAB
      based program was used to combine results of negative controls with actual
      casework DNA profiles to assess the probability that laboratory contaminants will
      give rise to reportable profiles (along with their likelihood ratios). Using data
      from an operational DNA unit as an example, it was demonstrated that the risk is
      inextricably linked to guidelines used to interpret DNA profiles. We have
      demonstrated how computer-based models can predict the levels of contamination
      expected in the process and, in addition, how the process can be made more robust
      by changing reporting guidelines. There is a need to compare DNA profiles against
      staff and plasticware elimination databases in order to determine sources of
      contamination. The likeliest outcome of a contamination event is false exclusion.

PMID- 15171166
TI  - Estimation of bullet striation similarity using neural networks.
AB  - A new method that searches for similar striation patterns using neural networks
      is described. Neural networks have been developed based on the human brain, which
      is good at pattern recognition. Therefore, neural networks would be expected to
      be effective in identifying striated toolmarks on bullets. The neural networks
      used in this study deal with binary signals derived from striation images. This
      signal plays a significant role in identification, because this signal is the key
      to the individually of the striations. The neural network searches a database for
      similar striations by means of these binary signals. The neural network used here
      is a multilayer network consisting of 96 neurons in the input layer, 15 neurons
      in the middle, and one neuron in the output layer. Two signals are inputted into
      the network and a score is estimated based on the similarity of these signals.
      For this purpose, the network is assigned to a previous learning. To initially
      test the validity of the procedure, the network identifies artificial patterns
      that are randomly produced on a personal computer. The results were acceptable
      and showed robustness for the deformation of patterns. Moreover, with ten
      unidentified bullets and ten database bullets, the network consistently was able
      to select the correct pair.

PMID- 15171165
TI  - The application of an automated allele concordance analysis system (CompareCalls)
      to ensure the accuracy of single-source STR DNA profiles.
AB  - A powerful method for validating a scientific result is to confirm specific
      results utilizing independent methodologies and processing pathways. Thus, we
      have designed, developed and validated an automated allele concordance analysis
      system (CompareCalls, patent pending) that performs comparisons between two
      independent DNA analysis platforms to ensure the highest accuracy for allele
      calls. Application of this system in a quality assurance role has shown the
      potential to eliminate greater than 90% of the STR analysis required of a DNA
      data analyst. While this system is broadly applicable for use with any two
      independent STR analysis programs, either prior to or following human data
      review, we are presenting its application to data generated with the ABI Prism
      Genotyper software system versus data generated with the SurelockID system. With
      the automated allele concordance analysis system, the GeneScan DNA fragment data
      generated from an ABI 377 gel image are analyzed in two independent pathways. In
      one analysis pathway, the GeneScan data are imported into Genotyper software
      where STR labels are assigned to the fragment data based upon the criteria of the
      Kazam 20% macro. The "Kazam" macro provided with the Genotyper program works by
      labeling all peaks in a category (or locus) and then filtering (or removing) the
      labels from peaks, such as those in stutter positions, that meet predefined
      criteria. In the second pathway, the GeneScan data are imported into the
      SurelockID analysis platform where STR labels and error messages are assigned to
      the fragment data based upon hard-coded allele calling criteria and quality
      parameters. The resulting STR allele calls for each analysis platform are then
      compared, utilizing the automated allele concordance analysis system. Any
      differences in the STR allele calls between the two systems are flagged in a
      discordance report for further review by a qualified DNA data analyst. The
      automated allele concordance analysis system guides the DNA data analyst to the
      discordant data generated by either analysis platform. Additionally, the analyst
      is also directed to data that are of less than pristine quality which may have an
      increased potential for errors in interpretation by either analysis platform or
      by a human DNA data analyst. Implementation of an automated allele concordance
      analysis system will yield high-quality data for CODIS and free the human DNA
      data analyst to perform other critical duties within the laboratory.

PMID- 15171167
TI  - Thermogravimetric analysis as a polymer identification technique in forensic
      applications.
AB  - This paper investigates the potential of thermogravimetric analysis (TGA) as a
      tool for determination of different species of polymers. Materials analyzed
      include polyvinyl chloride (PVC), chlorinated polyvinyl chloride (CPVC),
      polystyrene, polypropylene, nitriles, and nylon. Analyses showed excellent
      discriminating results even when samples were contaminated with silicates,
      organics, moisture, and char. The techniques developed were designed with a
      forensic-type analysis in mind, such as analysis of blast fragments and arson
      debris. Techniques were developed that gave satisfactory results even when sample
      sizes were less than five milligrams.

PMID- 15171168
TI  - A method for impregnating nylon transfer membranes with leucocrystal violet for
      enhancing and lifting bloody impressions.
AB  - The objective of this research project was to demonstrate a quick and easy method
      for impregnating nylon transfer membranes with leucocrystal violet (LCV) for the
      purpose of lifting and enhancing impressions made in blood. A stamp that would
      simulate fine detail found in fingerprints or footwear was used to create
      impressions on a variety of substrates. Four different LCV formulations were
      tested to determine the effectiveness of the prepared membranes in lifting and
      enhancing the impressions. Further investigation involved the feasibility of
      using the LCV membranes in the field by studying the shelf life and storage of
      the impregnated membranes and the longevity of the lifted impressions. One of the
      formations studied demonstrated superior lifting and enhancing capabilities, as
      well as a prolonged shelf life and a resilience of the lifted impressions, thus
      proving LCV to be an extremely valuable technique.

PMID- 15171169
TI  - Evaluation of 5-(4-nitrophenyl)-2,4-pentadien-1-al (NPPD) as a tracer for
      shadowing pursuits.
AB  - The chemical compound 5-(4-nitrophenyl)-2,4-pentadien-1-al (NPPD), called "spy
      dust," was used in the Soviet Union as a shadowing pursuit, the act of following
      someone secretly, for investigating the activities of diplomatic personnel. It is
      also useful for counter-terrorism, and some criminal cases in the forensic
      science field. In this paper, it was synthesized and evaluated as a tracer for
      shadowing pursuits. The method for utilizing this reagent was very simple: it was
      dissolved in methanol (1 mg/mL) and sprayed on the restricted area. If the
      suspect was to enter this area or touched the sprayed material, NPPD was attached
      to the suspect's shoe surface or hands. The color examination was a two-steps
      process: first was the addition of 1 mL of a 0.1% naphthoresorcinol methanol
      solution to the methanol extracts of a methanol-contained cotton swab used to
      smear some surfaces of the suspect, and second, the addition of 1 mL of
      concentrated hydrochloric acid, which turned the solution dark red. The gamma max
      of the colored solution was 510 nm, measured by ultraviolet-vis spectroscopy.
      Detection limits for three methods were determined: a visual method (detection
      limit 100 ng/3 mL), an ultraviolet-visible spectrometric method (detection limit
      10 ng/3 mL), and a selected-ion-monitoring gas chromatographic/mass spectrometric
      method (detection limit 300 pg/injection). The forensic utility of NPPD was
      demonstrated for two simulated cases: a theft case and a case where NPPD was used
      as a tracer to prove that an automobile had entered a restricted area. These
      examinations prove NPPD is a useful shadowing pursuit (spy dust) for the forensic
      science field.

PMID- 15171170
TI  - Identification of ascorbic acid and its degradation products in black powder
      substitutes.
AB  - Low explosives such as smokeless powder, black powder, and black powder
      substitutes have been used in illicit pipe bombings throughout the United States.
      Some of the newer black powder substitutes are formulated with ascorbic acid,
      which gradually decomposes as the powder ages, making it difficult if not
      impossible for the forensic chemist to identify it by traditional bulk
      techniques. A sensitive method for the identification of residual levels of
      ascorbic acid in black powder substitutes is presented. Powder samples are
      extracted with a mixture of acetonitrile and bis(trimethylsilyl)acetamide (BSA),
      which converts carboxylic acid and alcohol functional groups to trimethylsilyl
      esters and ethers, respectively. Samples are then analyzed by gas chromatography
      mass spectrometry (GC-MS). Results have shown that trace amounts of ascorbic acid
      can be identified at detection limits that are well below those for traditional
      bulk techniques. Degradation products for ascorbic acid (hydroxylated carboxylic
      acids, furanones, and lactones) can also be detected.

PMID- 15171171
TI  - Frequency of serial sexual homicide victimization in Virginia for a ten-year
      period.
AB  - The frequency of serial sexual murder has been widely discussed, and estimates of
      the number of victims in the United States range from 500 to 6000 per year. This
      study attempted to quantify the number of serial sexual murder victims in
      Virginia for a ten-year period. Multiple sources of data were utilized, including
      Federal Bureau of Investigation (FBI) case files, FBI's Violent Criminal
      Apprehension Program (ViCAP) reports, Virginia State Police ViCAP reports,
      Virginia Homicide Investigators Association, and the Virginia Division of
      Forensic Science DNA database, to effectively cull out all the known serial
      sexual murder victims for the given time period. Review of these records revealed
      a total of 28 victims of serial sexual murder, compared with a total of 5183
      murder victims for the same ten-year period. The frequency of serial sexual
      victimization was 0.5% of all homicides for the given period. These results
      highlight the unusual frequency of serial sexual murder.

PMID- 15171173
TI  - Recovery and identification of the victims of the Ehime Maru/USS Greeneville
      collision at sea.
AB  - This paper describes the recovery and identification of crew members lost during
      a collision at sea. On 9 February 2001, south of Honolulu, Hawaii, the Japanese
      fishing training boat, Ehime Maru was struck by the USS Greeneville (SSN 772), a
      Los Angeles-class fast attack submarine. Witnesses estimate that the vessel sank
      within 5-10 min after the collision. Nine of the 35 crew members remained
      unaccounted for after rescue procedures were completed. The U.S. Navy attempted
      the unprecedented procedure of moving the boat from a depth of 610 m (2000 ft)
      into shallower waters so that the missing could be located and recovered. Eight
      of the nine crew members were recovered and identified by their dental records.

PMID- 15171172
TI  - Radiographic survey of third molar development in relation to chronological age
      among Japanese juveniles.
AB  - The aim of the present study was to establish Japanese reference material on the
      third molar development of Japanese juveniles for forensic application.
      Observations were performed on the orthopantomograms of 1282 Japanese patients
      between the ages of 14.0 and 24.0 years. Demirjian formation stages of the
      maxillary and mandibular third molars were recorded for chronological evaluation
      of wisdom teeth and applied for further statistical analysis. Statistically
      significant differences were noted between the upper and lower jaws and genders.
      Accordingly, males achieved root developmental grades earlier than females. We
      assessed the mean ages for all formation grades and predicted the probability
      that a Japanese juvenile would be older than the relevant ages of 14, 16, and 20
      as defined by Japanese Juvenile Law. We determined the likelihood that a Japanese
      youth is older than the relevant age of 18 as defined by legislation in the
      United States.

PMID- 15171174
TI  - Sudden death associated with food and exercise.
AB  - Exercised-induced anaphylaxis occurs in conjunction with significant physical
      exertion. Anaphylaxis occurring when an individual exercise within a few hours of
      ingesting a particular food is an unusual variant. Cardiovascular symptoms can be
      the sole manifestation of exercise-induced food allergies, in which case death
      may mimic sudden cardiac death during physical exertion due to other pathologic
      causes. We report the sudden and unexpected death of an individual following the
      ingestion of hazelnuts and almonds, to which the individual was not previously
      known to be allergic. The decedent collapsed during vigorous dancing. The death
      was not associated with cutaneous or laryngeal manifestations of anaphylaxis.
      Awareness of the variable manifestations of food-precipitated anaphylaxis is
      necessary to correctly establish the diagnosis. An elevated serum tryptase level
      may be indicative of an allergic reaction, and allergen-specific IgE levels may
      be used to confirm the particular antigen.

PMID- 15171175
TI  - The significance of pulmonary interstitial emphysema in live birth determination.
AB  - The utility of pulmonary interstitial emphysema (PIE) in live birth determination
      is not well established. Because the distinction between live birth and
      stillbirth may be important in criminal proceedings, we undertook this study to
      investigate the relationship between the histologic finding of PIE and live
      birth. Sixty-six cases of infant death were retrieved and compared with 21
      stillborn infants. Histologic sections of the lungs were characterized as "florid
      PIE," "equivocal PIE," or "absent PIE." Sixteen cases of florid PIE were
      identified, all in live born infants. Forty-seven cases of equivocal PIE were
      found in 36 live born and 11 stillborn infants. In 24 cases (14 live born infants
      and 10 stillborns), no PIE was identified. We examined the relationship between
      florid PIE in infants with sudden infant death syndrome (SIDS) or "sudden
      unexpected death in infancy, manner undetermined" (SUDI), and also its
      relationship to other variables. No association was found. The presence of
      equivocal PIE may be an artifact of tissue processing. Florid PIE is found only
      in live born infants. No correlation between the presence of florid PIE and cause
      of death could be determined.

PMID- 15171176
TI  - The effect of time after body discovery on the accuracy of retrospective weather
      station ambient temperature corrections in forensic entomology.
AB  - Weather station data are used by forensic entomologists to estimate ambient
      temperatures at body discovery sites. Correlation data from sites may also be
      collected to correct for site and station differences. This experiment tested the
      accuracy over time of retrospective weather data correction using linear
      regression between stations and sites. Temperatures were logged at six
      hypothetical body discovery sites during a seven-day period for which a
      hypothetical body lay in situ, and a further four correlation periods. The
      accuracy of weather data for hypothetical body in situ periods improved after
      correction in 22 of 24 correlations; however, mean predicted body in situ
      temperatures for sites differed significantly between correlation periods.
      Predicted temperatures generally rose with time after body removal, which
      correlated with rising site temperatures accompanying seasonal change. Therefore,
      practitioners should be cautious in making correlations if weather patterns
      during correlation differ greatly from those while the body was in situ.

PMID- 15171177
TI  - A laboratory incubation method for determining the rate of microbiological
      degradation of skeletal muscle tissue in soil.
AB  - A controlled laboratory experiment is described, in principle and practice, which
      can be used for the of determination the rate of tissue decomposition in soil. By
      way of example, an experiment was conducted to determine the effect of
      temperature (12 degrees, 22 degrees C) on the aerobic decomposition of skeletal
      muscle tissue (Organic Texel x Suffolk lamb (Ovis aries)) in a sandy loam soil.
      Measurements of decomposition processes included muscle tissue mass loss,
      microbial CO2 respiration, and muscle tissue carbon (C) and nitrogen (N). Muscle
      tissue mass loss at 22 degrees C always was greater than at 12 degrees C (p <
      0.001). Microbial respiration was greater in samples incubated at 22 degrees C
      for the initial 21 days of burial (p < 0.01). All buried muscle tissue samples
      demonstrated changes in C and N content at the end of the experiment. A
      significant correlation (p < 0.001) was demonstrated between the loss of muscle
      tissue-derived C (Ct) and microbially-respired C (Cm) demonstrating CO2
      respiration may be used to predict mass loss and hence biodegradation. In this
      experiment Q10 (12 degrees C-22 degrees C) = 2.0. This method is recommended as a
      useful tool in determing the effect of environmental variables on the rate of
      decomposition of various tissues and associated materials.

PMID- 15171178
TI  - A preliminary investigation of the stages of adipocere formation.
AB  - Adipocere is a postmortem decomposition product which forms from a body's adipose
      tissue. This study aimed to chemically demonstrate the process of conversion from
      adipose tissue to adipocere. Samples of adipocere were collected from pig
      cadavers that were allowed to decompose for varying intervals. Samples of soil
      were collected from beneath the cadavers and analyzed to determine the leaching
      effect of adipocere. Gas chromatography/mass spectrometry (GC/MS) was used to
      quantify the fatty acid composition of pig adipocere. Fourier transform infrared
      spectroscopy (FTIR) was used as a confirmatory test and to identify other
      components such as triglycerides and calcium salts of fatty acids. The study
      demonstrates the process of adipocere formation and the stages of formation
      through which the process passes using chemical techniques.

PMID- 15171179
TI  - Fifteen-year retrospective study of infant organ weights and revision of standard
      weight tables.
AB  - No recent studies of organ weights of normal infants exist. We completed a 15
      year retrospective study of organ weights of normal infants who died between 1986
      and 2000 in an effort to update the "normal" weight standards for infants up to
      one year of age. Additionally, we compared organ weights of infants whose deaths
      were ruled Sudden Infant Death Syndrome (SIDS) with those of other natural or non
      natural causes within the same age groups, length and total body weight at
      autopsy, total organ weight as a percentage of total body weight, and with weight
      standards based on previous studies. This study included 453 autopsied infants in
      Kent County, Michigan, and who were referred to our facility by surrounding
      counties. All subjects were autopsied at Spectrum Health Blodgett Campus in Grand
      Rapids, Michigan.

PMID- 15171180
TI  - Esophageal and pharyngeal injuries associated with the use of the esophageal
      tracheal Combitube.
AB  - The Combitube is a ventilatory device consisting of a twin lumen tube with
      proximal and distal inflatable cuffs. The major benefit of the Combitube is that
      its design and function allow for ventilation through non-laryngoscope-assisted
      insertion into either the trachea, or esophagus. As with any invasive procedure,
      intubation using the Combitube carries certain risks and potential complications.
      The majority of complications are relatively minor; however, a rare and serious
      complication reported primarily in the anesthesiology literature is laceration of
      the esophagus. This reportedly rare injury is increasingly seen by medical
      examiners/coroners in the forensic setting. This paper presents a series of three
      cases of esophageal laceration and a single case of perforation of the
      hypopharynx associated with the use of the Combitube, while also exploring
      potential mechanisms of injury. In addition, this work demonstrates the vital
      role the medical examiner/coroner plays in identifying existing or potential
      problems with current or emerging medical devices.

PMID- 15171181
TI  - Unusual characteristic patterns of postmortem injuries.
AB  - Animal scavenging is one of the most significant causes of postmortem injuries. A
      large variety of scavenging animals have been reported on in previous papers.
      Although postmortem injuries attributable to birds are well known in the case of
      "aerial burial," the custom in Tibet, few cases of bird scavenging have been
      reported. In the two cases discussed herein, postmortem injuries were attributed
      to crows. Both cases, shared characteristic patterns of postmortem injuries, and
      in both cases death was attributed to fire. Although massive tissue loss by the
      crow scavenging made it difficult to determine the cause of the death and
      rendered personal identification difficult, 1 mL of blood drawn from the
      intracranial cavity and DNA analysis enabled this information to be determined,
      albeit with some difficulty.

PMID- 15171182
TI  - Suicide with a butcher's bolt.
AB  - The captive bolt pistol is an atypical firearm exclusively produced and used for
      butchery of breeding animals, but in some rare cases, it has been used as a
      lethal weapon for committing suicide by butchers, breeders and other people who
      have access to such weapons during their professional activities. This study
      describes the suicide committed by a butcher in the province of Udine (N. Italy)
      in 2001 who shot himself with his own captive bolt pistol that produced in the
      right temporal region a circular wound and a bone lesion of the temporal squama
      with a groove involving the frontal lobe; he died five days later of the fatal
      consequences of the meningo-encephalic lesions. The medico-legal issues
      implicated in this case, seen in the light of the data reported in the
      international literature, illustrate the difficulties faced when diagnosing these
      types of lesions, bearing in mind their rarity and peculiar nature, and introduce
      elements of differential diagnosis regarding lesions produced by similar weapons
      that lead to ascertainment of the event as accidental, suicidal, or homicidal.

PMID- 15171183
TI  - "Homicide by heart attack" revisited.
AB  - The sudden death of a person caused by an arrhythmia that is induced by physical
      and/or emotional stress provoked by the criminal activity of another person is
      sometimes referred to as "homicide by heart attack." Published criteria for such
      an event relate to situations where no physical contact occurs between the
      perpetrator and the victim. Situations involving physical contact, but with
      absence of lethal injuries, are frequently treated is a similar fashion by
      forensic pathologists. Herein, we propose a set of modified criteria, which
      include cases where physical contact has occurred. Five examples of so-called
      "homicide by heart attack" are presented, including a 40-year-old man who was
      struck in the head with a wooden statue, a 74-year-old man who was punched in the
      jaw by a robber, a 66-year-old woman who was started awake by a home-intruder, a
      67-year-old woman who struggled with a would-be purse-snatcher in a parking lot,
      and a 52-year-old man who was in a physical altercation with a younger man. In
      each instance, autopsy revealed the presence of severe, underlying heart disease,
      as well as absence of lethal injuries. In each case, investigative information
      was such that the emotional and/or physical stress associated with the criminal
      activity of another individual was deemed contributory to the death. The presumed
      mechanism of death in each case was a cardiac dysrhythmia related to underlying
      heart disease, but initiated by the emotional and/or physical stress.

PMID- 15171184
TI  - Homicide by manual occipitoatlantal dislocation.
AB  - Occipitoatlantal dislocation is usually seen as a fatal injury in traffic
      accidents and has rarely been reported as a consequence of a homicide. The
      authors report the case of a women presenting a fatal occipitoatlantal
      dislocation, the circumstances of which pointed to a homicidal origin. Blood
      extravasation surrounding the muscles of the posterior part of the neck as well
      as abnormal mobility of the cranio-cervical joint was noted during autopsy; thus
      a complete dissection of this region was performed. This led to the finding of a
      fracture of the left occipital condyle and of the left superior articular facet
      of the atlas. This case clearly demonstrates the need to perform a large,
      systematic, posterior approach to the upper cervical spine, completed by the
      opening of the skull around the posterior fossa, when injury to the cranio
      cervical junction is suspected. In these cases, the classic anterior approach
      give poor information and poor dissection possibilities.

PMID- 15171185
TI  - Psychiatric and neurological characteristics of murder defendants referred for
      pretrial evaluation.
AB  - After literature review, this paper presents the largest study to date (n = 270)
      of psychiatric and neurological characteristics of accused murderers in the
      United States. This retrospective record review of pretrial detainees undergoing
      competency to stand trial and criminal responsibility evaluations examined
      demographic characteristics, psychiatric diagnosis, substance use patterns,
      Intelligence Quotient (IQ), and results of electroencephalogram (EEG),
      neuroimaging (MRI or CT) and neurological examination. Substance use and
      mood/adjustment disorders were common. Neuroimaging was abnormal in 18% of
      subjects and was associated with lower Performance IQ. EEG and neurological exam
      findings were not associated with measured cognitive impairment. While 16% of
      subjects had a FS IQ < 70, only 6% were diagnosed with mental retardation.
      Subjects with a psychotic disorder (p = 0.001) or an anxiety disorder (p = 0.005)
      were more likely to use a knife than other subjects in the study. Violence risk
      assessment in these patients must not only involve inquiry about firearm
      availability.

PMID- 15171186
TI  - The use of an electrostatic detection device to identify individual and class
      characteristics on documents produced by printers and copiers--a preliminary
      study.
AB  - The market is inundated with inkjet printers, laser printers, and photocopiers,
      which are often used in criminal activities. Many of these office machines are
      built by various manufacturers, hence they are constructed with different
      hardware designs (e.g. "rolling" and "grabbing" mechanisms) that have changed
      over the years due to technological advances. Examinations of printed documents
      that involve the chemical analysis of ink colorants and the identification of
      physical machine defects such as trash marks are essential for the forensic
      examiner, but new techniques are needed to more closely identify a machine model
      or group of models. An electrostatic detection device (EDD) provide forensic
      examiners with a nondestructive method to examine indentations on a document. In
      this work, an EDD is used to detect latent physical markings left on documents by
      printers and photocopiers. Seventeen inkjet printers, 12 laser printers, and 3
      photocopy machines were used to produce test documents. Physical markings were
      detectable in the large majority of the documents and were reproducible 100% of
      the time.

PMID- 15171187
TI  - Screening postmortem whole blood for oxycodone by ELISA response ratios.
AB  - The objective of this study was to investigate the accuracy of screening
      postmortem whole blood for oxycodone using the ratio of the oxycodone immunoassay
      response to the response for the specimen obtained with a general opiate-class
      immunoassay. Fifty eight specimens which were negative for opiates and 158
      postmortem whole blood specimens positive for opiates including 66 specimens
      known to contain oxycodone were assayed. Specimens were diluted 1:5 with assay
      buffer and analyzed by both the Neogen Oxymorphone/Oxycodone ELISA and the Neogen
      Opiate Group ELISA (Neogen Corporation, Lexington KY). The oxycodone equivalents
      in ng/mL from the Oxymorphone/Oxycodone ELISA were divided by the morphine
      equivalents in ng/mL from the Opiates ELISA to obtain an Oxycodone/Opiates
      Response Ratio. This ratio was compared with the GC/MS data for all specimens and
      for opiate positive specimens. Receiver Operating Characteristic (ROC) analysis
      suggested that optimum relative response ratio was 2.0. The sensitivity of the
      ELISA response ratio for the presence of oxycodone at a response ratio cutoff of
      2.0 was 89.4% +/- 3.8% and the specificity was 88.1% +/- 3.2%. Specimens with a
      ratio of 2.0 or higher had a greater than 50% probability (positive predictive
      value) of containing oxycodone in a population with a greater than 15% prevalence
      of oxycodone.

PMID- 15171188
TI  - Sudden death caused by 1,1-difluoroethane inhalation.
AB  - A 20-year-old man was found dead on the floor next to a computer, with a nearly
      full can of "CRC Duster" dust remover located next to the deceased on the floor,
      and an empty can of the same product on the computer desk. Toxicologic evaluation
      using either gas chromatography/mass spectrometry (GC/MS) or gas
      chromatography/flame ionization detector (GC/FID) method identified the active
      ingredient 1,1-difluoroethane (Freon 152a) in all tissues analyzed. Tissue
      distribution studies revealed highest concentration in central blood, lung, and
      liver. It is believed that the 1,1-difluoroethane inhalation was the cause of
      death.

PMID- 15171189
TI  - Allele frequencies for two new Y-chromosome STR loci DYS598 and DYS607 in Chinese
      Han population (Shanxi area).

PMID- 15171190
TI  - Genetic profiles of five STR loci in eastern Chinese population.

PMID- 15171191
TI  - Allele frequencies of Y-chromosome STR loci DYS463 and DYS467 in a Chinese
      population.

PMID- 15171192
TI  - Autosomic STR loci (HUMTPOX, HUMTH01, HUMVWA, D18S535, D1S1656 and D12S391) in
      San Salvador (El Salvador, Central America).

PMID- 15171193
TI  - Human Y-chromosomal short tandem repeat DXYS156 in an Indian population sample.

PMID- 15171194
TI  - Commentary on: Gill JR, Lenz KA, and Amolat MJ. Gunshot fatalities in children
      and adolescents in New York City. J Forensic Sci 2003;48(4):832-35.

PMID- 15171195
TI  - Commentary on: Silva JA, Ferrari MM, Leong GB. The case of Jeffrey Dahmer: sexual
      serial homicide from a neuropsychiatric developmental perspective. J Forensic Sci
      2002 Nov;47(6):1347-59.

PMID- 15171196
TI  - Commentary on: Borrows DL, Hagardorn AN, Harlan GC, Wallen EDB, Ferslew KE. A
      fatal drug interaction between oxycodone and clonazepam. J Forensic Sci
      2003;48(3):683-86.

PMID- 15171197
TI  - Commentary on: Burrows DL, Hagardorn AN, Harlan GC, Wallen EDB, Ferslew KE. A
      fatal drug interaction between oxycodone and clonazepam. J Forensic Sci
      2003;48(3):683-86.

PMID- 15171198
TI  - Evidenced-based treatment places dentistry at the crossroads.

PMID- 15171199
TI  - Take it to the dental complaint department.

PMID- 15171200
TI  - Dental implants in the esthetic zone. Considerations for form and function.
AB  - Successful esthetic results of dental implant placement in the esthetic zone
      require knowledge of various concepts and techniques. Careful preoperative
      treatment planning, augmentation of hard and soft tissues, and attention to the
      details of implant surgical and prosthetic techniques are areas that must be
      addressed when treating the anterior maxilla. This article will address the
      fundamental considerations related to implant treatment in the anterior maxillary
      esthetic zone, using both theory and case examples.

PMID- 15171201
TI  - Myofibroblastic tumor of the oral cavity. A rare clinical entity.
AB  - Inflammatory myofibroblastic tumor is a rare clinical entity that can first
      present in the oral cavity. Though considered a benign lesion, it can behave very
      locally and aggressively, with significant bony destruction. A rare case of
      inflammatory myofibroblastic tumor is presented, along with the surgical
      treatment and an overview of this interesting clinical lesion.

PMID- 15171202
TI  - Stabilizing the number of New York State dental establishments.
AB  - Dental manpower and dental establishments are undergoing dramatic changes in New
      York State at a time when increases in the resident population of the state are
      limited. During the past decade there was a decrease of 700 licensed and
      registered dentists in the state. The average number of employees in dental
      establishments continues to increase. Between 1980 and 1995 there was an increase
      of more than 1,100 dental establishments in New York State. But since the mid
      1990s there was an increase of only 71 dental facilities in the state. These
      developments are considered in the various regions of the state.

PMID- 15171203
TI  - Contractual arrangements.

PMID- 15171204
TI  - Between innovation and tradition: the paradoxical relationship between eye
      movement desensitization and reprocessing and altered states of consciousness.
AB  - Eye movement desensitization and reprocessing (EMDR) is a relatively new form of
      psychotherapy to emerge in the West. Using both a case analysis and literature
      review we situate EMDR within the use of altered states of consciousness (ASCs)
      in psychological healing practices across times and cultures. We discuss EMDR's
      unique predicament as a therapy that draws upon techniques common to most
      therapeutic ASCs, while at the same time distancing itself from this tradition
      through its pseudoscientific language and technologic aesthetic. Our conclusion
      attempts to shed light on this paradox and raise questions for further study.

PMID- 15171205
TI  - Testimonial psychotherapy for adolescent refugees: a case series.
AB  - Adolescent refugees are a traumatized, vulnerable group of arrivals to America
      who lack experience with or interest in psychiatric care. Testimonial
      psychotherapy's unique focus on transcribing personal, traumatic events for the
      altruistic purpose of education and advocacy make it an acceptable interaction by
      which to bridge the cultural gap that prevents young refugees from seeking
      psychiatric care. The theoretical basis for testimony is discussed. Testimonial
      psychotherapy has been used with adult refugees, but not with adolescents. This
      article describes the testimonial process with three Sudanese adolescents (the so
      called 'Lost Boys'), which appeared feasible and safe. An efficacy study is
      underway.

PMID- 15171206
TI  - Reconceptualizing the sequelae of political torture: limitations of a psychiatric
      paradigm.
AB  - A psychiatric model of traumatization has informed most research in psychology on
      the effects of human rights violations, including political torture, in South
      Africa. This article highlights some of the limitations of a hegemonic
      psychiatric approach to conceptualizing current sequelae of abuse experienced by
      political detainees during the apartheid era. It calls attention to the relevance
      of the South African social and political context in which survivors are located,
      methodological problems that characterize psychological research on trauma in
      South Africa and other developing countries, and the relevance of the meaning
      that survivors may attribute to their experience of detention and torture.

PMID- 15171207
TI  - Self systems, cultural idioms of distress, and the psycho-bodily consequences of
      childhood suffering.
AB  - In this article, I examine the effects of childhood suffering in two cases--one
      from my anthropological fieldwork in the central highlands of Sulawesi in
      Indonesia and one from my psychotherapeutic practice in Los Angeles. I argue that
      although people will always carry with them the psycho-bodily signature of their
      past social experience, these signatures are affected by the cultural idioms of
      distress into which they are woven and from which psycho-bodily attention is
      channeled and given meaning (or not). However, I also suggest that past social
      experiences are related to life trajectories in very complicated ways. For
      example, while the enactment of a cultural idiom of distress may help to resolve
      or give meaning to a form of illness or distress, it also may cause or exacerbate
      other forms of suffering--depending on how it is used and articulated by any
      given individual.

PMID- 15171208
TI  - Finding a fit: psychiatric pluralism in south India and its implications for WHO
      studies of mental disorder.
AB  - This article examines reports of improvement and decline in short-term follow-up
      interviews and long-term recollections among patients in three forms of therapy
      for mental illness in south India: ayurvedic (indigenous) psychiatry, allopathic
      (western) psychiatry, and religious healing. Interviews indicate that patients of
      all three therapeutic systems showed improvement after follow-up assessments and
      that several patients had radically divergent experiences with each of the three
      therapies; each therapy was found by some to be helpful and by others to be
      ineffective. These findings suggest that a greater availability of distinct forms
      of therapy makes it more likely that an individual will find a therapy to which
      he or she responds well, an insight that helps interpret World Health
      Organization-sponsored studies which examined mental disorders in developed and
      developing country sites and found a better outcome for these disorders in
      developing country centers. Although several studies have attempted to account
      for this difference in outcome, none have done so by considering that the
      'developing' country sites in the World Health Organization studies are all
      places that have a greater availability of diverse forms of therapy when compared
      with the 'developed' sites.

PMID- 15171209
TI  - Maternal cognitions about distress and anxiety in young Latino children with
      disruptive behaviors.
AB  - This study was undertaken to describe how Caribbean Latina mothers understand
      distress in children, the behaviors that they attribute to it, and the labels
      that they use to express their cognitions. Findings from 62 mothers of young
      children with disruptive behaviors indicated that mothers made attributions about
      anxiety in 40% of the children with a high likelihood of clinical anxiety.
      Hyperactive and restless behavior, but not children's fears, was understood by
      mothers to reflect anxiety. References to 'nervios' could be categorized into: an
      illness condition, a crisis condition, and a temperament type. Only temperament
      usage was applied to children.

PMID- 15171210
TI  - The use of international videoconferencing as a strategy for teaching medical
      students about transcultural psychiatry.
AB  - Videoconferencing is an innovative method that potentially allows medical
      students exposure to international teachers in refugee mental health who would
      otherwise be inaccessible. This article reports a pilot study using
      videoconferencing with international teachers from Australia, Sweden and the USA
      participating in the training of ten senior Swedish medical students. Interviews
      with an actual and a simulated patient were conducted at the U.S. and Australian
      sites respectively, followed by discussions involving those two sites with
      students and their supervisors in Sweden. Students evaluated the method
      favourably, as did the teachers, although the brevity of the program was seen as
      a limitation. Teachers noted the importance of preparing students and patients
      and ensuring that the technology operates smoothly to ensure success. Although
      cost-effective in teaching medical students in developed countries,
      videoconferencing may still be out of the reach of training programs in many
      developing countries where it is most needed.

PMID- 15171211
TI  - Knowledge structures in illness narratives: development and reliability of a
      coding scheme.
AB  - Illness narratives reflect patients' underlying illness schemas or models of
      illness as well as efforts to position themselves vis-a-vis a specific
      interlocutor and social context. Although the literature on illness narratives in
      medical anthropology has been dominated by the explanatory model perspective,
      people may use other types of knowledge structures to frame and construct their
      conceptions of symptoms. For this study, we developed operational definitions and
      a coding manual for three types of putative knowledge schemas: prototypes, chain
      complexes, and explanatory accounts. The operationalized definitions were then
      applied to coding a sample of illness narratives collected in a study of help
      seeking in an urban community population. It was found that all three knowledge
      structures could be reliably identified in these narratives. This method of
      analysis provides a way to test hypotheses regarding the role of knowledge
      structures in illness narratives.

PMID- 15171212
TI  - Manuscript retraction.

PMID- 15171213
TI  - [Strategy for bacterial translocation in acute pancreatitis].
AB  - Although bacterial translocation (BT) is thought to be a main cause of secondary
      pancreatic infection, the clinical significance is still unclear. Therefore, we
      investigated relationship between pancreatic infection and BT, analyzing the
      results of treatments such as continuous regional arterial infusion of protease
      inhibitor and antibiotics (CRAI), selective digestive decontamination, and early
      enteral nutrition (SDD/EN) in 45 severe acute pancreatitis patients. The
      infection rate of 17 cases without CRAI, SDD/EN was 58.8%, and mortality was
      23.5%. Antibiotics-resistant bacteria, such as methicillin-resistant
      Staphylococcus aureus (MRSA) was often proven in infected pancreatic tissue.
      Whereas, in 16 cases who underwent both therapy, only one patient died of multi
      organ failure (6.3%). Pseudomonas aeruginosa and K. pneumoniae were proven from
      his feces before pancreatic infection coincidence, and, in autopsy, these
      bacteria and MRSA were proved from necrotic pancreatic tissue. BT must be large
      cause of secondary pancreas infection, because CRAI and SDD/ EN prevent secondary
      pancreatic infection. But we must consider other infection routes, and
      development of antibiotics resistant bacteria.

PMID- 15171214
TI  - [Study on the effects of tetramethylpyrazine on tumor cells: survey and
      prospects].

PMID- 15171222
TI  - Current awareness on yeast.

PMID- 15171223
TI  - The Cat Group policy statement 6. Cats and toxoplasmosis: what are the risks?

PMID- 15171221
TI  - Live discussion: how the other half lives - or the what, how, and where, of the
      AbetaPP intracellular domain.

PMID- 15171224
TI  - The timing of the blood pressure measurement may affect the result in patients
      with acute stroke.

PMID- 15171225
TI  - The multinational Men's Attitudes to Life Events and Sexuality (MALES) study: I.
      Prevalence of erectile dysfunction and related health concerns in the general
      population.
AB  - OBJECTIVE: The aims of the Men's Attitudes to Life Events and Sexuality (MALES)
      study were to identify prevalence of erectile dysfunction (ED) and related health
      issues in the general male population in Europe, North and South America, and to
      examine the attitudes and behavior of men in relation to these health issues.
      RESEARCH DESIGN AND METHODS: Phase I of the MALES study involved 27839 men aged
      20-75 years who were interviewed in eight countries (United States, United
      Kingdom, Germany,France, Italy, Spain, Mexico, and Brazil) using a standardized
      questionnaire. Phase II of the MALES study involved 2912 men who were recruited
      from the sub-sample of Phase I MALES participants who reported ED together with
      additional men with ED recruited from other sources. MAIN OUTCOME MEASURE:
      Prevalence of ED and associated attitudes. RESULTS: The overall prevalence of ED
      in the MALES sample was 16%. ED prevalence varied markedly by country, however,
      from a high of 22%of men in the US reporting ED to a low of 10% in Spain. The
      prevalence of self-reported ED increased with increasing age. Men with co-morbid
      medical conditions and risk factors, including cardiovascular disease,
      hypertension, dyslipidemia,and depression all reported higher prevalence of ED.
      Men with ED also reported increased prevalence rates of these co-morbid
      conditions. MALES Phase II data indicated that among men who reported ED, 58% had
      actively sought medical attention for their condition; however, only 16% of men
      with ED were currently being treated with oral PDE-5 therapy. CONCLUSIONS: The
      MALES study confirms the high prevalence rates of ED and its association with co
      morbid medical conditions, such as diabetes and depression, reported in other
      large-scale, epidemiological studies. Despite the advent of oral
      phosphodiesterase inhibitors, only 58% of ED sufferers consult a physician about
      their problem, and only 16% of men with self-reported ED maintain their use of
      oral therapy.

PMID- 15171226
TI  - Effect of atorvastatin on high density lipoprotein cholesterol and its
      relationship with coronary events: a subgroup analysis of the GREek Atorvastatin
      and Coronary-heart-disease Evaluation (GREACE) Study.
AB  - OBJECTIVE: To investigate the relationship between changes in high density
      lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for
      coronary heart disease (CHD)-related events in the secondary CHD prevention GREek
      Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings
      suggested that dose titration with atorvastatin (10-80 mg/day, mean 24
      mg/day)achieves the National Cholesterol Educational Program treatment goals and
      significantly reduces morbidity and mortality, in comparison to usual care.
      METHODS: Analysis of variance was used to assess the effect of atorvastatin on
      HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent
      multivariate Cox predictive model,involving backward stepwise logistic
      regression,was used to evaluate the relation between coronary events and HDL-C
      changes. RESULTS: The mean increase in HDL-C levels during the study was 7%. All
      doses of atorvastatin significantly increased HDL-C levels. Increases were
      greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4%
      for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile
      (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors
      of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95%
      confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase
      in HDL-C. CONCLUSIONS: There was a significant beneficial effect on HDL-C levels
      across the dose range of atorvastatin. Clinical outcomes in the structured care
      arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C
      increase. This effect was independent from benefit induced by low density
      lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction
      associated with a rise in a low HDL-C at baseline remains significant under
      aggressive (-46%) LDL-C lowering conditions. However, the relationship between
      HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.

PMID- 15171227
TI  - Medicaid program; provider qualifications for audiologists. Final rule.
AB  - This final rule will revise the requirements for audiologists furnishing services
      under the Medicaid program. As a result, the requirements will create consistency
      with the Medicare program's definition of a qualified audiologist by recognizing
      State licensure in determining provider qualifications. These revised standards
      will expand State flexibility in choosing qualified audiologists.

PMID- 15171228
TI  - Procedures for designating classes of employees as members of the Special
      Exposure Cohort under the Energy Employees Occupational Illness Compensation
      Program Act of 2000; Final rule. Final rule.
AB  - This document describes how the Department of Health and Human Services ("HHS")
      will consider designating classes of employees to be added to the Special
      Exposure Cohort under the Energy Employees Occupational Illness Compensation
      Program Act of 2000 ("EEOICPA''). Under EEOICPA, and Executive Order 13179, the
      Secretary of HHS is authorized to make such designations, which take effect 180
      days after Congress is notified unless Congress provides otherwise. An individual
      member (or the eligible survivors of a member) of a class of employees added to
      the Special Exposure Cohort would be entitled to compensation if the Department
      of Labor ("DOL") finds that employee incurred a specified cancer and the claim
      meets other requirements established under EEOICPA.

PMID- 15171229
TI  - Notification that new names and new combinations have appeared in volume 54, part
      1, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles).

PMID- 15171230
TI  - Issue celebrating the 80th birthday of Maria Wollemann.

PMID- 15171231
TI  - Abstracts of the 18th Annual Meeting of the Japanese Society for Neural Growth,
      Regeneration and Transplantation.

PMID- 15171232
TI  - How asset tests block low-income Medicare beneficiaries from needed benefits.
AB  - The Medicare Savings Programs and Medicaid help elderly Medicare beneficiaries
      with their cost-sharing responsibilities and provide much-needed additional
      benefits. But 40 to 50 percent of eligible low-income Medicare beneficiaries are
      not enrolled in the Medicare Savings Programs. One persistent barrier is the use
      of asset tests, which greatly complicate the application process for applicants
      and program staff. Older people with low incomes generally have few assets and
      the income and assets of older people who qualify for public programs do not
      change substantially over time. Findings suggest that use of asset tests should
      be eliminated or asset limits should be increased; at a minimum, cost-of-living
      adjustments should be made. Findings also indicate that the renewal process
      should be simplified, and use of verification documents should be reduced or
      eliminated.

PMID- 15171233
TI  - Lysosomal diseases: pathophysiology and therapy. Proceedings and abstracts of the
      3rd International Symposium on Lysosomal Storage Diseases. Santiago de
      Compostela, Spain, May 2003.

PMID- 15171234
TI  - Primary and preventive care: periodic assessments.

PMID- 15171235
TI  - Proceedings and abstracts of the 4th International Research Workshop on Alopecia
      Areata. Washington, DC, USA, October 31-November 2, 2002.

PMID- 15171236
TI  - [Use of animals in experimental tests].

PMID- 15171238
TI  - [Using rats from a closed laboratory colony for toxicology tests--pathological
      view].

PMID- 15171237
TI  - Expression of kinin receptor mRNA in the HPA axis of type 1 and type 2 diabetic
      rats.
AB  - mRNA levels of kinin B1 and B2 receptors were determined in HPA axis of type 1
      (STZ-induced) and type 2 diabetic rats (ZDF and obese Zucker rats). B2 mRNA
      levels were elevated in hypothalamus of STZ-induced diabetic (STZ-D) and ZDF
      rats. Pituitary B2 mRNA levels were elevated in ZDF and obese rats. Adrenal B2
      mRNA level was attenuated in STZ-D rats. Kinin B1 receptor may not play a role in
      HPA axis in diabetes since its expression was unchanged. Enhanced mRNA expression
      of B2 receptors in hypothalamus of STZ-D and ZDF rats parallels a rise in plasma
      glucose and reflect a functional relationship. Enhanced pituitary B2 mRNA in type
      2 and reduced adrenal in type 1 diabetes account for a differential pattern in
      release of transmitters.

PMID- 15171239
TI  - [A closed colony of laboratory rats].

PMID- 15171240
TI  - [Genetic control of closed laboratory rats--an international standard].

PMID- 15171241
TI  - Unprecedented spread of avian influenza requires broad collaboration.

PMID- 15171242
TI  - WHO and UNAIDS unveil plans for 3 by 5 AIDS programme.

PMID- 15171243
TI  - Health professions applaud the WHO 3 by 5 initiative to bring treatment to AIDS
      sufferers.

PMID- 15171244
TI  - Beyond the double helix: writing and reading the histone code.
AB  - Chromatin is the physiological carrier of not only genetic information, encoded
      in the DNA, but also of epigenetic information including DNA methylation and
      histone modifications. As such histone modifications are involved in many aspects
      of nuclear processes including gene regulation and chromosome segregation.
      Recently, a 'histone code' hypothesis was put forward to explain how patterns of
      histone modification may function in downstream processes. In support of the
      'histone code' hypothesis, we found in vivo and in vitro evidence that effector
      proteins, HP1 (heterochromatin protein 1) and Pc (Polycomb) can discriminate and
      'read' histone methylation marks on K9 and K27, respectively. Moreover, we
      propose a 'binary switch' model and suggest that binding and release of effector
      proteins to their cognate sites can be regulated by modifications on adjacent or
      nearby residues. Thus, combinations of adjacent histone modifications would
      function differently from singular modification, and static modifications (e.g.
      Lys methylation) may well be regulated by dynamic modifications (e.g.
      phosphorylation). Finally, we describe a novel histone phosphorylation event
      linking the function of Mst1 kinase and H2B Ser14 phosphorylation with apoptotic
      chromatin condensation in vertebrates. As this modification is not found during
      mitotic chromosome condensation, these findings suggest the intriguing
      possibility that a unique 'death' mark exists for chromatin condensation during
      apoptosis.

PMID- 15171245
TI  - The indexing potential of histone lysine methylation.
AB  - Diverse post-translational modifications of histone N-termini represent an
      important epigenetic mechanism for the organization of chromatin structure and
      the regulation of gene activity. Within the last three years, great progress has
      been made in understanding the functional implications of histone methylation, in
      particular through the characterization of histone methyltransferases (HMTases)
      that direct the site-specific methylation of lysine positions in the histone H3 N
      terminus. Histone lysine methylation has been linked with pericentric
      heterochromatin formation, X-inactivation, Polycomb group (Pc-G)-dependent gene
      repression and epigenetic control of transcription units at euchromatic
      positions. Together, these regulatory roles have strongly established histone
      lysine methylation as a central epigenetic modification for the organization of
      eukaryotic chromatin. However, they also create a paradox: if histone lysine
      methylation is present at so many chromatin regions, how can it impart epigenetic
      information? We provide evidence that differences in distinct methylation states
      (mono- vs. di- vs. trimethylation) and selective combinations of individually
      methylated lysine positions can indeed index chromatin regions, resulting in
      epigenetic landmarks for the partitioning of eukaryotic chromatin.

PMID- 15171246
TI  - A model for step-wise assembly of heterochromatin in yeast.
AB  - Gene silencing involves the assembly of DNA into specialized chromatin domains
      that are inaccessible to trans-acting factors and are epigenetically inherited.
      In the budding yeast Saccharomyces cerevisiae, silent heterochromatic DNA domains
      occur at telomeres, the silent mating type loci, and the rDNA repeats. At
      telomeres and the mating type loci, silencing requires the Sir2, Sir3 and Sir4
      proteins, the conserved N-termini of histones H3 and H4, and a number of
      chromatin assembly factors. The Sir proteins form a multimeric complex that binds
      preferentially to deacetylated nucleosomes through the Sir3 and Sir4 subunits.
      The Sir2 subunit possesses an unusual NAD-dependent deacetylase activity that is
      required for silencing at each of the above loci. Recent studies have shown that
      silent chromatin domains are assembled in a step-wise manner involving sequential
      cycles of deacetylation and SIR complex binding. Sir2-dependent deacetylation is
      specifically required for the spreading of the complex to regions beyond
      nucleation sites but not for its initial binding to DNA at the mating type loci
      and telomeres. A distinct Sir2 complex called RENT is required for silencing at
      rDNA. In contrast to telomeres and the mating type loci, Sir2 activity is not
      required for association of RENT with rDNA.

PMID- 15171247
TI  - H2B ubiquitylation and de-ubiquitylation in gene activation.
AB  - Previous models for the role of histone modifications suggest that adding and
      removing modifications, such as acetylation/deacetylation in gene regulation, are
      functionally antagonistic. We have investigated a transcriptional role of H2B C
      terminal ubiquitylation and de-ubiquitylation in Saccharomyces cerevisiae. H2B
      ubiquitylation is required for optimal transcription of SUC2 and GAL1 genes. The
      ubiquitin hydrolase Ubp8 is a stable component of SAGA but not ADA complexes, and
      is not required for overall integrity of SAGA. Biochemical and genetic evidence
      indicates that Ubp8 targets H2B for deubiquitylation. The dynamic balance of H2B
      ubiquitylation/deubiquitylation is important for GAL1 transcription since either
      substitution of the ubiquitylation site in H2B (Lys123), or loss of Ubp8, lowers
      GAL1 expression. Further, this balance of ubiquitylation appears to set the
      balance of histone H3 methylation at Lys4 relative to Lys36. Thus, unlike
      acetylation/deacetylation whose functions are mutually opposing, both
      ubiquitylation and de-ubiquitylation are required for gene activation. These
      results suggest that ubiquitylation of histones has a unique role among histone
      modifications, possibly to orchestrate an ordered pathway of chromatin
      alterations.

PMID- 15171248
TI  - Structural and chemical basis of histone acetylation.
AB  - Histones are the predominant protein components of chromatin and are subject to a
      variety of specific post-translational modifications that are correlated with
      transcriptional competence. Among these modifications are reversible acetylation
      that is mediated by acetyltransferases that mediate transcriptional activation
      and deactylases that mediate transcriptional repression and gene silencing.
      Structural studies have provided important insights into the mechanism of
      substrate specific binding and catalysis by the enzymes that mediate reversible
      acetylation. In this paper I will review structural work from my laboratory on
      histone acetyltransferases (HATs) and the Sir2 family of histone deacetylases
      (HDACs), with a specific focus on catalysis and substrate-specific binding by
      these enzymes.

PMID- 15171249
TI  - Phosphorylation and acetylation of histone H3 at inducible genes: two
      controversies revisited.
AB  - The phosphorylation and acetylation (phosphoacetylation) of histone H3 tails
      concomitant with gene activation is now well established and has been observed at
      several inducible genes. However, two aspects of this response have been
      controversial. The first relates to the identity of the kinase that
      phosphorylates histone H3. Experiments with Coffin-Lowry cells purporting to show
      that Rsk2 was the histone H3 kinase have proven to be irreproducible. The second
      relates to the proposition that histone H3 phosphorylation and acetylation are
      'synergistic and coupled' in mammalian cells. But here too, some of the
      experiments have not been reproducible and some of the key statements
      contaminated by issues of antibody specificity. More recent studies indicate that
      H3 phosphorylation and acetylation are independently targeted to the same histone
      H3 tail.

PMID- 15171250
TI  - HDAC7 regulates apoptosis in developing thymocytes.
AB  - Central immune tolerance is established in the thymus for T cells via a complex
      selection process that involves interactions between CD4+CD8+ double-positive
      thymocytes and antigen-presenting cells. Cells that express antigen receptors
      interacting strongly with self peptide MHC complexes are deleted from the
      repertoire via activation-induced apoptosis, a process termed negative selection.
      Cells that express an appropriate signal are positively selected and mature into
      single positive naive T cells, either CD4 or CD8 positive. The balance between
      positive and negative selection is thought to play a critical role in the
      elimination of self-reactive clones and in the establishment of central immune
      tolerance. We have recently reported that HDAC7, a class II histone deacetylase,
      is highly expressed in CD4+CD8+ double positive thymocytes. HDAC7 inhibits Nur77
      expression, an orphan receptor involved in antigen-induced cell death and in
      negative selection. The inhibitory effect of HDAC7 on the Nur77 promoter is
      mediated via the transcription factor MEF2D. During T cell receptor activation,
      HDAC7 is exported from the nucleus leading to the derepression of Nur77
      expression and the induction of apoptosis. These observations define HDAC7 as a
      regulator of Nur77 and apoptosis in developing thymocytes and indicate that HDAC7
      is likely to play an important role in the control of central immune tolerance.

PMID- 15171251
TI  - Dual roles of histone deacetylases in the control of cardiac growth.
AB  - Diverse aetiological factors, including myocardial infarction, hypertension and
      contractile abnormalities, trigger a cardiac remodelling process in which the
      heart becomes abnormally enlarged with a consequent decline in cardiac function
      and eventual heart failure. Pathological cardiac hypertrophy is accompanied by
      the activation of a fetal cardiac gene programme, which contributes to
      maladaptive changes in contractility and calcium handling. Traditional treatment
      for heart failure involves administration of drugs that antagonize early
      signalling events at or near the cell membrane (e.g. cell surface receptor or ion
      channels). Given the complexity and redundant nature of the signalling networks
      that drive cardiac pathogenesis, a potentially more efficacious therapeutic
      strategy for disrupting the disease process would be to target common downstream
      elements in pathological signalling cascades. We have shown that class II histone
      deacetylases (HDACs) suppress cardiac hypertrophy, and mice lacking class II
      HDACs are sensitized to hypertrophic signals. Paradoxically, HDAC inhibitors also
      block cardiac hypertrophy and fetal gene activation. Based on these findings, we
      propose that distinct HDACs play positive or negative roles in the control of
      cardiac growth by regulating opposing sets of target genes via their interactions
      with different sets of transcription factors.

PMID- 15171252
TI  - Chromatin modifications as clues to the regulation of antigen receptor assembly.
AB  - Changes in chromatin structure play a key role in the regulation of the mammalian
      genome, governing diverse processes including transcription, replication and
      recombination. In the earliest stages of antigen receptor assembly, D and J
      segments of the immunoglobulin heavy chain (IgH) and T cell receptor (TCR) beta
      loci are recombined in B and T cells respectively, while the V segments are not.
      Distinct distribution patterns of various histone modifications and the
      nucleosome-remodelling factor Brg1 are found at recombinationally 'active' (DJ)
      and 'inactive' (V) regions, offering a means independent of transcription or
      DNAse I hypersensitivity to define chromatin domains at these loci. Within some
      inactive loci marked by H3-K9 dimethylation, two distinct levels of methylation
      are found in a non-random, gene-segment specific pattern. Brg1 is not localized
      to specific sequences, as it is with transcriptional initiation, but rather
      associates with the entire active locus in a pattern that mirrors acetylation of
      histone H3. Distinct 'hotspots' of histone H3 dimethylated at lysine 4 are
      localized at the ends of the active DJ domains of both the IgH and TCRbeta loci,
      suggesting they may serve as important marks for locus accessibility. The
      specific patterns of modification imply that the regulation of V(D)J
      recombination involves recruitment of specific methyltransferases in a localized
      manner.

PMID- 15171253
TI  - The HDAC complex and cytoskeleton.
AB  - HDAC6 is a cytoplasmic deacetylase that dynamically associates with the
      microtubule and actin cytoskeletons. HDAC6 regulates growth factor-induced
      chemotaxis by its unique deacetylase activity towards microtubules or other
      substrates. Here we describe a non-catalytic structural domain that is essential
      for HDAC6 function and places HDAC6 as a critical mediator linking the
      acetylation and ubiquitination network. This evolutionarily conserved motif,
      termed the BUZ domain, has features of a zinc finger and binds both mono- and
      polyubiquitinated proteins. Furthermore, the BUZ domain promotes HDAC6 mono
      ubiquitination. These results establish the BUZ domain, in addition to the UIM
      and CUE domains, as a novel motif that both binds ubiquitin and mediates mono
      ubiquitination. Importantly, the BUZ domain is essential for HDAC6 to promote
      chemotaxis, indicating that communication with the ubiquitin network is critical
      for proper HDAC6 function. The unique presence of the UIM and CUE domains in
      proteins involved in endocytic trafficking suggests that HDAC6 might also
      regulate vesicle transport and protein degradation. Indeed, we have found that
      HDAC6 is actively transported and concentrated in vesicular compartments. We
      propose that an integration of reversible acetylation and ubiquitination by HDAC6
      may be a novel component in regulating the cytoskeleton, vesicle transport and
      protein degradation.

PMID- 15171254
TI  - Tat acetylation: a regulatory switch between early and late phases in HIV
      transcription elongation.
AB  - The HIV transcriptional activator Tat enhances the processivity of RNA polymerase
      II by recruiting the CyclinT1/CDK9 complex to the TAR RNA element. In addition,
      Tat synergizes with the histone acetyltransferase p300 and is acetylated by p300
      at a single lysine residue (K50) in the TAR RNA binding domain. We have recently
      reported that this post-translational modification is necessary for the
      interaction and transcriptional synergy of Tat with the transcriptional
      coactivator PCAF. We have further studied the relevance of Tat acetylation during
      HIV transcription and generated antibodies specific for acetylated Tat (AcTat).
      Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in
      cells. Similarly, the specific p300 inhibitor Lys-CoA and short inhibitory RNAs
      specific for p300 suppressed Tat transcriptional activity. Full-length synthetic
      AcTat bound to TAR RNA and CyclinT1 with high affinity, but formation of the Tat
      TAR-CyclinT1 ternary complex was inhibited when K50 was acetylated. Our data
      collectively show that Tat acetylation by p300 defines a critical step in Tat
      transactivation that serves to disrupt the Tat/TAR/CyclinT1 complex and helps in
      recruiting PCAF to the elongating RNA polymerase II.

PMID- 15171255
TI  - Dynamics of the p53 acetylation pathway.
AB  - The p53 tumour suppressor exerts anti-proliferative effects, including growth
      arrest, apoptosis and cell senescence, in response to various types of stress.
      However, p53 is a short-lived protein and its activity is maintained at low
      levels in normal cells. Numerous studies indicate that CBP/p300-mediated acetyl
      transferase activity is critical for its role in both catalysing p53 acetylation
      and activating p53-mediated function during stress response. Interestingly, two
      additional regulators have also been identified in the p53 acetylation pathway.
      PID/MTA2 is a p53-interacting protein that induces p53 deacetylation by
      recruiting the HDAC1 complex. Subsequent work has also identified Sir2alpha, a
      NAD-dependent histone deacetylase that can attenuate p53 transcriptional activity
      through deacetylation. The prominence of deacetylase activity on p53 certainly
      raises the defining question of its physiological purpose. It is likely that
      deacetylation proxides a quick acting mechanism to stop p53 function once
      transcriptional activation of target genes is no longer needed. We present data
      indicating that both HDAC1 and Sir2alpha are critical for p53-dependent stress
      response. Furthermore, we also try to define the functional consequence of p53
      acetylation at the molecular level. Finally, we propose a model regarding the
      differential roles of HDAC1 and Sir2alpha in the regulation of p53 function.

PMID- 15171257
TI  - Reversal of gene silencing as a therapeutic target for cancer--roles for DNA
      methylation and its interdigitation with chromatin.
AB  - It has become apparent over the past several years that one of the attractive
      emerging prevention and therapy targets for cancer is the reversal of aberrant
      gene silencing mediated by epigenetic events associated with transcriptional
      repression. Integral to the possibilities for this targeting is the need to
      dissect the molecular mechanisms which underlie these transcriptional changes. At
      present, the best studied of the epigenetically silenced genes involved in cancer
      are those which harbour aberrant DNA promoter region methylation. This growing
      list includes almost half of all proven tumour suppressor genes and also a
      rapidly expanding list of genes with candidate roles for antitumour activities as
      well. Thus, one approach receiving much attention for restoring expression of
      abnormally silenced cancer genes for therapeutic purposes is utilization of
      agents such as 5-azacytidine (5-AzaC) and 5'-deoxy-azacytidine (DAC), which
      inhibit the DNA methyltransferases (DNMTs) that catalyse DNA methylation. Other
      approaches, and particularly the notion of utilizing inhibitors of histone de
      acetylation, are being suggested by the exploding body of data concerning the
      role of histone modifications in mediating gene expression status, and especially
      those parameters that participate in gene silencing. Importantly, these histone
      parameters, which are the focus of this Novartis Foundation Symposium, are not
      only tightly linked to mechanisms through which DNA methylation participates in
      gene silencing, but are also being integrally linked to how abnormal patterns of
      this DNA modification may actually arise in tumour cells. In this brief review,
      it is hypothesized that these interactions between DNA methylation and histone
      modifications may have to be targeted to most effectively exploit the potential
      for using reversal of gene silencing as an approach to cancer prevention and
      treatment.

PMID- 15171256
TI  - Regulation of NF-kappaB action by reversible acetylation.
AB  - While the proximal cytoplasmic signalling events controlling the activation of NF
      kappaB are understood in considerable detail, the subsequent intranuclear events
      that regulate the strength and duration of NF-kappaB action remain poorly
      defined. Recently, we have demonstrated that the RelA subunit of the NF-kappaB
      heterodimer is subject to reversible acetylation. The p300/CBP acetyltransferases
      play a major role in the in vivo acetylation of RelA principally targeting
      lysines 218, 221 and 310 for modification. Acetylation of these distinct lysine
      residues regulates different functions of NF-kappaB, including transcriptional
      activation, DNA binding affinity, I-kappaBalpha assembly and subcellular
      localization. Specifically, acetylation of lysine 221 enhances DNA binding and
      impairs assembly with I-kappaBalpha while acetylation of lysine 310 is required
      for full transcriptional activity of RelA independent of changes in DNA binding
      or I-kappaBalpha binding. In turn, acetylated RelA is deacetylated by histone
      deacetylase 3 (HDAC3). Deacetylation of lysine 221 promotes high-affinity binding
      of RelA to newly synthesized I-kappaBalpha proteins whose expression is activated
      by NF-kappaB. I-kappaBalpha binding to deacetylated RelA promotes rapid nuclear
      export of the NF-kappaB complex. This export is dependent on CRM1 binding to a
      nuclear export signal present in I-KBalpha and promotes replenishment of the
      cytoplasmic pool of latent NF-kappaB/I-kappaBalpha complexes thus readying the
      cell for response to the next NF-kappaB inducing stimulus Together, these studies
      highlight how reversible acetylation of RelA serves as an intranuclear molecular
      switch promoting both positive and negative regulatory effects on nuclear NF
      kappaB action.

PMID- 15171258
TI  - Transcription regulation by histone deacetylases.
AB  - Dynamic changes in the post-translational modification pattern of histories such
      as acetylation, deacetylation, phosphorylation, methylation and ubiquitination
      are thought to provide a code for correct regulation of gene expression by
      affecting chromatin structure and interaction with regulatory factors. Our
      studies focus on the role of histone deacetylases (HDACs) in transcriptional
      regulation and addressing functional differences of class I and class II HDACs.
      To identify genes that were transcriptionally regulated by specific HDACs, genome
      scale expression profiles were performed in cancer cells following the inhibition
      of three HDAC family members by specific oligonucleotides. The modulated genes
      identified in this study represented a wide range of modifications in different
      cellular pathways. In addition, treatment of cancer cells with a HDAC inhibitor
      was found to induce the expression of the small GTPase RhoB through an inverted
      CCAAT box in the RhoB promoter. These studies identified a specific transcription
      element involved in HDAC-mediated gene transcription and genes that are
      transcriptionally regulated by specific HDACs, providing important insight into
      the potential therapeutic benefit of HDAC inhibition.

PMID- 15171259
TI  - Molecular and cellular basis for the anti-proliferative effects of the HDAC
      inhibitor LAQ824.
AB  - We have developed a cinnamic hydroxamic class of histone deacetylase inhibitors
      of which a prototype was designated as NVP-LAQ824. NVP-LAQ824, inhibits histone
      deacetylase enzymatic activities in vitro and transcriptionally activated the p21
      promoter in reporter gene assays. When tested on a variety of solid tumour cell
      lines, NVP-LAQ824 exhibited selective anti-proliferative effects, inducing cell
      growth inhibition in some, while inducing cell death in others. To induce cell
      death, a minimum of 16 h exposure to NVP-LAQ824 is required. Flow cytometry
      studies revealed that both tumour cell lines and normal diploid fibroblasts
      arrested in the G2/M phase of the cell cycle after compound treatment. However,
      an increased sub-G1 population at 48 h (reminiscent of apoptotic cells) was only
      observed in the cancer cell lines. Annexin V staining data confirmed that NVP
      LAQ824 induced apoptosis in tumour cells, but not in normal cells. To relate HDAC
      inhibition to the anti-proliferative effects of NVP-LAQ824, expression of HDAC 1
      was inhibited using antisense and this was sufficient to activate p21 expression,
      hypophosphorylate Rb and inhibit cell growth. Furthermore, tumour cells treated
      with NVP-LAQ824 caused acetylation of HSP90 and degradation of its cargo
      oncoproteins. Finally, NVP-LAQ824 exhibited antitumour effects in a xenograft
      animal model. To determine if NVP-LAQ824 inhibited histone deacetylases in vivo,
      tumours treated with the drug were immunoblotted with an antibody specific for
      acetylated histones H3 and H4 and the results indicated increased histone H3 and
      114 acetylation levels in NVP-LAQ824 treated cancer cells. Together, our data
      indicated that the activity of NVP-LAQ824 was consistent with its intended
      mechanism of action. This novel HDAC inhibitor is currently in clinical trials as
      an anticancer agent.

PMID- 15171260
TI  - Histone deacetylase inhibitors: development as cancer therapy.
AB  - Histone deacetylase (HDAC) inhibitors represent a new class of targeted
      anticancer agents. A number of structural classes of HDAC inhibitors have been
      developed of which several are in clinical trials, including phenylbutyrate (PB)
      and related compounds; the hydroxamic acids, suberoylanilide hydroxamic acid
      (SAHA) and depsipeptide (FK-228); and the benzamides, MS-275 and C1-994. This
      review will focus on our studies with the hydroxamic acid HDAC inhibitors, of
      which SAHA is the lead agent. X-ray crystallographic studies with a HDAC
      homologue (HDLP) demonstrated that the hydroxamic acid group, most of the
      aliphatic chain and part of the phenyl amino group of SAHA inserts into the
      pocket-like catalytic site of the enzyme, at the base of which is a zinc
      molecule. SAHA inhibits the activity of class I and II HDACs and is selective in
      altering gene expression. SAHA is synergistic in its anticancer activity with
      radiation, kinase inhibitors, cytotoxic agents and differentiating agents. In
      phase I clinical trial with orally administered SAHA the agent caused
      accumulation of acetylated histones in peripheral mononuclear cells and tumour
      cells, has excellent bioavailability and has shown antitumour activity in
      patients with haematologic and solid tumours.

PMID- 15171261
TI  - The origins and development of the Cardiovascular Program at Hartford Hospital.
      150th Anniversary of Hartford Hospital.

PMID- 15171262
TI  - Awareness about factors that affect the management of hypertension in Puerto
      Rican patients.
AB  - INTRODUCTION: There are few published reports describing the health status of
      Hispanic populations in the United States with chronic illnesses, such as
      hypertension. Most studies on hypertension in Hispanics are on Mexican-Americans
      and little data exist for other Hispanic subgroups, such as Puerto Ricans. Health
      related issues specific to a particular Hispanic subgroup may not be
      generalizable to all Hispanics. Patients' perceptions and awareness of health
      related issues specific to a particular medical condition play an important role
      in the management and outcome. OBJECTIVE: The primary objective of the study is
      to determine if patients' general perceptions of hypertension, hypertension
      related risk factors, complications, and life-style behavior modifications
      correlated with various patient demographics, such as age, gender, primary
      language, education level, socioeconomic status, marital status, health insurance
      category, and employment status. The working hypothesis is that patients who are
      older, unmarried, less educated, Spanish-speaking only, unemployed, and have low
      income, are more likely to report lack of awareness to various hypertension
      related issues. SETTING: Hospital-based ambulatory center with major emphasis on
      providing care to underserved populations of the surrounding community, of which
      Puerto Ricans comprised the predominant ethnic group. STUDY DESIGN: A single,
      bilingual interviewer administered a series of questions to Hispanic,
      hypertensive patients. Questions were divided into the following seven
      categories: patient knowledge and perception of the disease; diet and salt
      intake; tobacco use; alcohol use; weight control and exercise; and medication and
      alternative therapy use. Within each category were various questions designed to
      study the patients' knowledge of hypertension, self-reported compliance with
      behavior modifications, and patient education on these behaviors. Data from 19
      Puerto Rican patients were collected and chi-square tests and pothoc power
      analyses were performed. Responses to the various questions were correlated to
      patient demographics and socioeconomic variables. RESULTS: Use of herbal teas
      correlated significantly with the patients' primary language. Twenty-one percent
      of the patients who spoke Spanish only used herbal teas for treatment of their
      hypertension. All patients who reported herbal medication or tea use had a middle
      school education. There were many trends towards statistical significance in the
      following categories: patient perceptions and level of formal education; patient
      knowledge of hypertension and language spoken; salt intake and years of
      schooling; and correlation of herbal use with employment status, health insurance
      statu, and age. CONCLUSION: Additional research must be undertaken with larger
      sample sizes to give validity and statistical significance to the observed
      findings. This study and previous research, demonstrate some of the special
      issues that may need to be considered in the delivery of health care to specific
      Hispanic patient populations.

PMID- 15171263
TI  - Safety of liver biopsy in acute sickle hepatic crisis.
AB  - Hepatic dysfunction is a commonly recognized complication of sickle cell crisis.
      The cause of hepatic compromise is usually made evident from physical
      examination, clinical history, laboratory testing, and noninvasive imaging. There
      are occasions when liver biopsy is required to define the etiology of the hepatic
      dysfunction. Liver biopsy during acute sickle hepatic crisis can result in
      hemorrhage and death. Careful consideration of alternatives must be explored
      prior to performing liver biopsy on a patient with acute sickle hepatic crisis.
      If biopsy cannot be delayed, close hemodynamic monitoring of the patient
      postbiopsy is essential.

PMID- 15171264
TI  - Can a multidisciplinary initiative to increase adverse drug reaction reporting
      work?

PMID- 15171265
TI  - A short history of the Department of Medicine at Hartford Hospital.

PMID- 15171266
TI  - The evolution of trauma and emergency medicine.
AB  - One hundred and fifty years ago Hartford Hospital was created in response to a
      major disaster and traumatic event. The field of traumatology and emergency
      medicine has grown through adolescence and is now a mature program at Hartford
      Hospital and a full department within the University of Connecticut School of
      Medicine. It will continue its mission to provide excellence in clinical care to
      ill and injured citizens as well as to educate all levels of practitioners and
      report results of scientific investigations and programmatic developments within
      the specialty.

PMID- 15171267
TI  - The doctors of Hartford Hospital 1954-2004: a personal memoir.

PMID- 15171268
TI  - The hospital as cultural melting pot.

PMID- 15171269
TI  - Anniversary tribute.

PMID- 15171270
TI  - 150 years of caring: a tribute to colleagues past and present.

PMID- 15171271
TI  - Hartford Hospital, 1960 to 1965.

PMID- 15171272
TI  - Congratulations.

PMID- 15171273
TI  - University of Connecticut Hartford linkage.

PMID- 15171274
TI  - Reflections on training at Hartford Hospital.

PMID- 15171275
TI  - On the University of Connecticut education link in internal medicine with
      Hartford Hospital.

PMID- 15171276
TI  - Elution control of microparticles with a coupled acoustic-gravity field and
      orthogonal laminar flow.
AB  - Particles accumulated in a coupled acoustic-gravity field, in which the base
      material of a particle determines the equilibrium aggregation positions, are
      eluted from a separation channel by an orthogonal laminar flow. Elution times are
      controllable by changing the intensity and frequency of the ultrasonic waves.

PMID- 15171277
TI  - Voltammetric response of phenylboronic acid monolayer-modified gold electrode to
      sugars.
AB  - The surface of a gold (Au) disk electrode was modified with a self-assembled
      monolayer consisting of phenylboronic acid moiety to fabricate a voltammetric
      sensor sensitive to sugars. The modified Au electrode exhibited a voltammetric
      response to sugars in the presence of Fe(CN)6(3-) ion in the sample solution at
      neutral pH. The peak current of the cyclic voltammograms decreased depending on
      the type and concentration of sugars. The dynamic range of the electrode is 3 -
      100 mM for glucose and mannose and 1 - 30 mM for fructose. The sugar sensor can
      be used repeatedly after rinsing in 10 mM acetate buffer (pH 4.5).

PMID- 15171278
TI  - Advance of computational technology for simulating solvent extraction.
AB  - Due to recent significant enhancement of computer performance as well as
      computational techniques, molecular modeling and molecular simulations using
      computational chemistry can be achieved at the level of practical applications.
      Even in solvent extraction, the application of computational chemistry to
      simulations of extraction processes and the molecular design of high-performance
      extracting agents have gradually been increasing during the last decade. With
      combining the quantitative structure-property relationship between the molecule
      properties calculated by the computational chemistry methods and the
      thermodynamic properties obtained from experiments, researchers can precisely
      predict the next-generation of extracting agents and novel extraction processes.
      In this review, the concept of computational chemistry, such as molecular
      mechanics, molecular orbitals and molecular dynamics calculations, frequently
      used in the filed of solvent extraction, are outlined. Our systematic research on
      the solvent-extraction process utilizing MM, MO and MD calculations is also
      presented.

PMID- 15171279
TI  - Recent advances in the analysis of steroid hormones and related drugs.
AB  - The development during the last 15 years and the state-of-the-art in the analysis
      of bulk steroid hormone drugs and hormone-like structures and pharmaceutical
      formulations made thereof are summarized. Other steroids (sterols, bile acids,
      cardiac glycosides, vitamins D) as well as biological-clinical aspects and
      pharmacokinetic and metabolic studies are excluded from this review. The state-of
      the-art is summarized based on comparisons of monographs in the latest editions
      of the European Pharmacopoeia, United States Pharmacopoeia and the Japanese
      Pharmacopoeia. This is followed by sections dealing with new developments in the
      methodology for the fields of spectroscopic and spectrophotometric,
      chromatographic, electrophoretic and hyphenated techniques as well
      electroanalytical methods. The review is terminated by two problem-oriented
      sections: examples on impurity and degradation profiling as well as enantiomeric
      analysis.

PMID- 15171280
TI  - An application of plastic microchannel-microheater chips to a thermal synthetic
      reaction.
AB  - Polystyrol microchannel-microheater chips were fabricated on the basis of
      imprinting and photolithography techniques. The solution (i.e., methanol)
      temperature in the vicinity of the microheater (width = 100 or 200 microm and
      length = 100 microm) integrated in the channel (width = 100 microm and depth = 20
      microm) was evaluated on the basis of the temperature-dependent fluorescence
      lifetime of Rhodamine B as a function of a flow rate and the voltage applied to
      the heater. The study demonstrated that the fabricated chip acted certainly as a
      microheater. The chip was then applied to the thermal reaction between
      benzaldehyde and malononitrile in methanol. Under optimum conditions,
      benzilidenemalononitrile as the product of the reaction was obtained in a 96%
      yield with the reaction time of 84 s.

PMID- 15171281
TI  - Solid-phase microextraction for the evaluation of partition coefficients of a
      chlorinated dioxin and hexachlorobenzene into humic substances.
AB  - We developed a method for the evaluation of the partition coefficients (K(oc)) of
      hexachlorobenzene (HCB) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD)
      into humic substances (HSs) by using solid-phase microextraction (SPME). In the
      aqueous solution containing HCB or HpCDD and HS, the unbound species of HCB or
      HpCDD were accumulated on the SPME fiber. Subsequently, HCB or HpCDD on the SPME
      fiber was directly analyzed by GC-ECD. When the concentration of organic carbon
      in HS ([OC]) was plotted against the ratio of [HCB] or [HpCDD] in the absence of
      HS to that in the presence of HS, linear relationships were observed. The slope
      of the line corresponded to the K(oc) value. The log K(oc) values for HCB and
      HpCDD evaluated were in the ranges of 3.9 - 4.9 and 5.9 - 7.2, respectively.
      These values were the same order as those in the literature, which were evaluated
      by other methods (e.g., solubility enhancement, solid-phase extraction and
      dialysis). The relative standard deviations of the log K(oc) values evaluated in
      this study were within 5%.

PMID- 15171282
TI  - Evaluation of a microwave-assisted extraction technique for the determination of
      polychlorinated biphenyls and organochlorine pesticides in sediments.
AB  - A microwave-assisted extraction (MAE) technique for the determination of
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in marine
      sediment samples has been investigated. The analytes were extracted under
      different treatment conditions, such as temperature, time and extraction solvent.
      They were quantified by an isotope-dilution method, and the observed
      concentrations and recovery yields obtained under different conditions were
      compared. The results of a comparison between this MAE and other extraction
      techniques, such as pressurized fluid extraction, saponification, sonication, and
      Soxhlet extraction, are also given in this report. The techniques gave comparable
      results with the values obtained by other extraction techniques and the certified
      values in the samples. However, the observed concentration values of mono- and
      dichlorinated biphenyls varied depending on the extraction temperature.

PMID- 15171283
TI  - Native fluorescence flow-through optosensor for the fast determination of
      diphenhydramine in pharmaceuticals.
AB  - A single, rapid flow-through optosensor spectrofluorometric system is proposed
      for the determination of diphenhydramine in different pharmaceutical
      preparations. This sensor was developed in conjunction with a monochannel flow
      injection analysis system with fluorometric solid-phase transduction.
      Diphenhydramine was directly injected into a carrier stream of ethanol/water, 50%
      (v:v), and transitorily retained on a sorption gel Sephadex G-15 placed in the
      detection area into the cell. The determination was carried out without any
      derivatization reaction by directly measuring the intrinsic fluorescence of the
      analyte and using the peak height as an analytical signal. The chemical and
      instrumental variables were optimized, and the influence of some foreign
      substances that can be found in typical pharmaceutical samples containing
      diphenhydramine was also investigated. Diphenhydramine could be determined in the
      concentration ranges of 0.5 - 8 microg ml(-1) and 0.1 - 1.2 microg ml(-1) with
      detection limits of 0.088 and 0.019 microg ml(-1) at sampling rates of 30 and 19
      h(-1) for 200 and 800 microl of the sample volume, respectively.

PMID- 15171284
TI  - [Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]manganese(III) acetate as a
      novel carrier for a selective iodide PVC membrane electrode.
AB  - [5,10,15,20-Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]Mn(III) acetate
      (MnTDPAc) was applied as an ionophore for an iodide-selective PVC membrane
      electrode. The influences of the membrane composition, pH of the test solution
      and foreign ions on the electrode performance were investigated. The sensor
      exhibited not only excellent selectivity to iodide ion compared to Cl- and
      lipophilic anions such as ClO4- and salicylate, but also a Nernstian response
      with a slope of -59.4 +/- 1.2 mV per decade for iodide ions over a wide
      concentration range from 1.0 x 10(-2) to 7.5 x 10(-6) M at 25 degrees C. The
      potentiometric response was independent of the pH of the solution in the pH range
      of 2 - 8. The electrode could be used for at least 2 months without any
      considerable divergence in the potential. Good selectivity for iodide ion, a very
      short response time, simple preparation and relatively long-term stability were
      the silent characteristics of this electrode. It was successfully used as an
      indicator electrode in the potentiometric titration of iodide ions, and also in
      the determination of iodide from seawater samples and drug formulations.

PMID- 15171285
TI  - Mercury(II) ion-selective electrodes based on p-tert-butyl calix[4]crowns with
      imine units.
AB  - A PVC membrane incorporating p-tert-butyl calix[4]crown with imine units as an
      ionophore was prepared and used in an ion-selective electrode for the
      determination of mercury(II) ions. An electrode based on this ionophore showed a
      good potentiometric response for mercury(II) ions over a wide concentration range
      of 5.0 x 10(-5) - 1.0 x 10(-1) M with a near-Nernstian slope of 27.3 mV per
      decade. The detection limit of the electrode was 2.24 x 10(-5) M and the
      electrode worked well in the pH range of 1.3 - 4.0. The electrode showed a short
      response time of less than 20 s. The electrode also showed better selectivity for
      mercury(II) ions over many of the alkali (Na+, -1.69; K+, -1.54), alkaline-earth
      (Ca2+, -3.30; Ba2+, -3.32), and heavy metal ions (Co2+, -3.67; Ni2+, -3.43; Pb2+,
      -3.31; Fe3+, -1.82). Ag+ ion was found to be the strongest interfering ion. Also,
      sharp end points were obtained when the sensor was used as an indicator electrode
      for the potentiometric titration of mercury(II) ions with iodide and dichromate
      ions.

PMID- 15171286
TI  - Coated wire silver-ion selective electrode based on a N,N'-bis(2
      thienylmethylene)-1,2-diaminobenzene.
AB  - A novel membrane coated platinum-wire electrode (MCPWE) based on N,N'-bis(2
      thienylmethylene)-1,2-diaminobenzene (BTMD) for highly selective determination of
      Ag+ ion has been developed. The influences of membrane composition and pH on the
      potentiometric responses of electrode were investigated. The potentiometric
      responses are independent of the pH of the test solution in the range of 5.0 -
      9.0. The electrode shows a linear response for Ag+ ion over the concentration
      range of 1.0 x 10(-60 to 1.0 x 10(-1) M with a lower detection limit of 6.0 x 10(
      7) M. The electrode possesses a Nernstian slope of 59.7 mV decade(-1) and a fast
      response time of < or = 17 s and can be used for at least 2 months without any
      observable deviation. The proposed electrode displayed very good selectivity for
      Ag+ ion with respect to NH4+ and alkali, alkaline earth and some common
      transition metal ions. The practical utility of the electrode has been
      demonstrated by its use as the indicator electrode in the potentiometric
      titration of an AgNO3 solution with a NaI solution and in determination of the
      silver content of a developed radiological film.

PMID- 15171287
TI  - Voltammetric determination of tinidazole using a glassy carbon electrode modified
      with single-wall carbon nanotubes.
AB  - An electrochemical method based on a single-wall carbon nanotubes (SWNTs) film
      coated glassy carbon electrode (GCE) was described for the determination of
      tinidazole. In a 0.1 M Britton-Robinson buffer with a pH of 10.0, tinidazole
      yields a very sensitive and well-defined reduction peak at -0.78 V (vs. SCE) on a
      SWNTs-modified GCE. Compared with that on a bare GCE, the reduction peak of
      tinidazole increases significantly on the modified GCE. Thus, all of the
      experimental parameters were optimized and a sensitive voltammetric method is
      proposed for tinidazole determination. It is found that the reduction peak
      current is proportional to the concentration of tinidazole over the range from 5
      x 10(-8) to 4 x 10(-5) M, and that the detection limit is 1 x 10(-8) M at 3 min
      open-circuit accumulation. This new analysis method was demonstrated with
      tinidazole drugs.

PMID- 15171288
TI  - Differential pulse anodic stripping voltammetric determination of traces of
      copper with a tobramycin-Nafion modified electrode.
AB  - A Nafion-modified glassy carbon electrode incorporated with tobramycin for the
      voltammetric stripping determination of Cu2+ has been explored. The electrode was
      fabricated by tobramycin containing Nafion on the glassy carbon electrode
      surface. The modified electrode exhibited a significantly increased sensitivity
      and selectivity for Cu2+ compared with a bare glassy carbon electrode and the
      Nafion modified electrode. Cu2+ was accumulated in HAc-NaAc buffer (pH 4.6) at a
      potential of -0.6 V (vs. SCE) for 300 s and then determined by differential pulse
      anodic stripping voltammetry. The effects of various parameters, such as the mass
      of Nafion, the concentration of tobramycin, the pH of the medium, the
      accumulation potential, the accumulation time and the scan rate, were
      investigated. Under the optimum conditions, a linear calibration graph was
      obtained in the concentration range of 1.0 x 10(-9) to 5.0 x 10(-7) mol l(-1)
      with a correlation coefficient of 0.9971. The relative standard deviations for
      eight successive determinations were 4.3 and 2.9% for 1.0 x 10(-8) and 2.0 x 10(
      7) mol l(-1) Cu2+, respectively. The detection limit (three times signal to
      noise) was 5.0 x 10(-10) mol l(-1). A study of interfering substances was also
      performed, and the method was applied to the direct determination of copper in
      water samples, and also in analytical reagent-grade salts with satisfactory
      results.

PMID- 15171289
TI  - Determination of anion-exchange resin performance based on facile chloride-ion
      monitoring by FIA-spectrophotometry with applications to water treatment
      operation.
AB  - Based on a flow-injection spectrophotometry, an automatic analytical method for
      determination of ppb-level chloride-ion has been established. By use of this
      method, a novel FIA method for the determination of SBAER performance has also
      been developed. In this paper, the effects of concentration, dosage, and flow
      rate of the regenerant on BEC of SBAER were first investigated dynamically by the
      FIA method. In addition, the flow rate of the sample water and the temperature of
      the ion exchange resin were also examined. The optimum conditions were obtained:
      the volume of the regenerant (sodium hydroxide) was 50 mL (0.15 g resin), and its
      concentration was 3% (w/v); the volumetric flow rates of the regenerant and the
      sample water were 0.5 ml/min (4.3 m/h) and 1.5 ml/min (13 m/h), respectively. The
      exchanging temperature was 25 +/- 5 degrees C. The method is characterized by the
      use of a micro resin-column, shorter testing cycle, easy operation, and high
      reproducibility. The proposed method is approximately 30 times more efficient
      than the manual method, and it can be used for the exchange performance
      comparison of various SBAER.

PMID- 15171290
TI  - Flow-injection and sequential-injection determinations of paracetamol in
      pharmaceutical preparations using nitrosation reaction.
AB  - A simple FI and two different SI systems have been investigated for the
      determination of paracetamol by employing a simple reagent for a nitrosation
      reaction. It is based on the on-line nitrosation of paracetamol with sodium
      nitrite in an acidic medium. The formed nitroso derivative species reacts further
      with sodium hydroxide to convert it to a more stable compound. The yellow product
      is continuously monitored at 430 nm. The FI system is very simple and cost
      effective for fast manual operation (60 injections/h; y = 0.268x + 44.314, r2 =
      0.9910 for 400 - 1000 mg/l and y = 0.1687x + 145.72, r2 = 0.9970 for 1000 - 2500
      mg/l). The two SI systems with different components and configurations are
      automated and optimized for the conditions for which no extra dilution is to be
      required for sample handling: one with a syringe pump and two selection valves
      (60 samples/h; y = 0.1488x - 4.7297, r2 = 0.9946 for 400 - 1000 mg/l and y =
      0.0858x + 63.933, r2 = 0.9849 for 1000 - 2500 mg/l); the other is simpler and
      more cost-effective, with an autoburette and only one selection valve (15
      samples/h; y = 0.0072x + 1.1467, r2 = 0.9977 for 200 - 1000 mg/l and y = 0.0028x
      + 5.4699, r2 = 0.9879 for 1000 - 2500 mg/l). They have all been applied to assay
      paracetamol in pharmaceutical preparations. The obtained results agree with those
      by the US Pharmacopeia method.

PMID- 15171291
TI  - Simultaneous extraction of Cr(III) and Cr(VI) with a dithiocarbamate reagent
      followed by HPLC separation for chromium speciation.
AB  - A simultaneous extraction of Cr3+ and Cr6+ species in aqueous solution was
      developed. The extraction behaviors of ammonium pyrrolidinedithiocarbamate (APDC)
      for both Cr6+ and Cr3+ are carefully discussed in this report. X-ray diffraction
      and spectroscopic studies indicate that Cr6+ reacts with the ammonium
      pyrrolidinedithiocarbamate ligand to form two products, Cr(PDC)2(OPDC) and
      Cr(PDC)3, where OPDC represents an oxygen insertion between Cr and S atoms. A
      high concentration of APDC in the phthalate buffer under an elevated temperature
      (50 degrees C) was applied in solvent extraction (SE) to increase the extraction
      efficiency of Cr3+, so that both Cr3+ and Cr6+ could be extracted by APDC
      simultaneously. The complex involving the oxygen insertion bonding Cr-O-S is
      separable from the normal Cr(PDC)3 complex chromatographically, thus allowing the
      quantification of Cr6+. The major product of Cr6+ has a structure of
      Cr(PDC)2(OPDC) and the minor product is Cr(PDC)3 with a ratio of
      Cr(PDC)2(OPDC)/Cr(PDC)3 being 8.5. The extraction conditions for Cr6+ and Cr3+ as
      well as the chromatographic separation of the complexes using high-performance
      liquid chromatography (HPLC) are reported. Potential applications for the
      chemical speciation of chromium by SE/HPLC in environmental aqueous solutions are
      also discussed.

PMID- 15171292
TI  - Synthesis, characterization of silica gel phases-chemically immobilized-4
      aminoantipyrene and applications in the solid phase extraction, preconcentration
      and potentiometric studies.
AB  - Two new 4-aminoantipyrene chemically-immobilized silica gel phases: ii (N,N
      donor) and iii (N,O-donor), were synthesized and characterized by IR and surface
      coverage determination. The latter was accomplished by thermal desorption and
      metal probe methods, giving 0.300 and 0.312 mmol g(-1) for ii and 0.220 and 0.250
      mmol g(-1) for iii. Moreover, potentiometric titration provided a surface
      coverage of 0.323 mmol g(-1) for ii. The metal capacity values in mmol g(-1) of
      ii, iii and the active silica gel phase i for a series of di- and trivalent metal
      ions were determined at pH 1.0 - 6.7. Phase i showed the lowest values, while ii
      and iii reflected higher affinity toward most of the metal ions. The highest
      values were 0.300 for Hg(II)-ii and 0.220 mmol g(-1) for Cd(II)-iii. Distribution
      coefficients (log Kd) were in the range of 3.57 - 4.76 for ii and 2.32 - 3.46 for
      iii, thus confirming certain selectivity characters of the solid extractors. The
      application of the phases as solid extractors and preconcentrators for some heavy
      metal ions is presented. Good percentage extraction and removal of 94 - 98 +/- 4 
      6% of the spiked 1.000 microg ml(-1) of Hg(II), Cd(II), Pb(II), Cu(II) and
      Zn(II) and good percentage recovery of 94 - 99 +/- 3 - 6% of 50 ng ml(-1) of
      these ions from tap water samples were obtained. Stability constants of H(I) and
      Cu(II) with ii for the two-phase mixture at 25 degrees C and I = 0.1 (KCI) were
      determined potentiometrically. The pKa of ii are 5.6 and 8.4, while the log K
      values for CuHL and CuL (L = ii) are 6.3 and 5.8, respectively, leading to the
      determination of several analytical data for Cu(II)-ii.

PMID- 15171293
TI  - Selective extraction of iron(III) from aqueous nitrate solution in the presence
      of cobalt(II), copper(II) and nickel(II) ions using bis(delta2-2-imidazolinyl)
      5,5'-dioxime.
AB  - The feasibility of using bis(delta2-2-imidazolinyl)-5,5'-dioxime (H2L) for the
      selective extraction of iron(III) from aqueous solutions was investigated by
      employing an solvent-extraction technique. The extraction of iron(III) from an
      aqueous nitrate solution in the presence of metal ions, such as cobalt(II),
      copper(II) and nickel(II), was carried out using H2L in binary and multicomponent
      mixtures. Iron(III) extraction has been studied as a function of the pH,
      equilibrium time and extractant concentration. From the extracted complex species
      in the organic phase, iron(III) was stripped with 2 M HNO3, and later determined
      using atomic-absorption spectrometry. The extraction was found to significantly
      depend on the aqueous solution pH. The extraction of iron(III) with H2L increases
      with the pH value, reaching a maximum in the zone of pH 2.0, remaining constant
      between 2 and 3.5 and subsequently decreasing. The quantitative extraction of
      iron(III) with 5 x 10(-30 M H2L in toluene is observed at pH 2.0. H2L was found
      to react with iron(III) to form ligand complex having a composition of 1:2
      (Fe:H2L).

PMID- 15171294
TI  - Determination of volatile compounds in Magnolia bark by microwave-assisted
      extraction coupled to headspace solid-phase microextraction and gas
      chromatography-mass spectrometry.
AB  - A method is described for the determination of volatile compounds in Magnolia
      bark using microwave-assisted extraction coupled to headspace solid-phase
      microextraction (MAE-HS-SPME), followed by gas chromatography with mass
      spectrometry (GC-MS). Parameters affecting the extraction efficiency, such as
      sampling time and temperature, microwave irradiation power and desorption time,
      were investigated to achieve the optimal conditions. The result obtained was
      compared with that of steam distillation; only small differences existed between
      these two methods. Therefore, the proposed method seems to be a feasible and
      relatively simple, fast and solvent-free procedure for identification of
      essential oils in Magnolia bark.

PMID- 15171295
TI  - Titania as a chemo-affinity support for the column-switching HPLC analysis of
      phosphopeptides: application to the characterization of phosphorylation sites in
      proteins by combination with protease digestion and electrospray ionization mass
      spectrometry.
AB  - A method for the determination of phosphorylation sites in phosphoproteins based
      on column-switching high-performance liquid chromatography (HPLC) has been
      developed. The HPLC system consisted of a titania precolumn for the selective
      adsorption of phosphopeptides, an anion-exchange analytical column and a UV
      detector (215 nm). Rabbit muscle phosphorylase a (RPa) and porcine stomach pepsin
      (PSP) were tested as model phosphoproteins. After protease digestion, the
      resulting phosphopeptides were successfully isolated by column-switching HPLC.
      The phosphopeptide fractions were analyzed by electrospray ionization mass
      spectrometry with a positive or negative ion mode after purification by reversed
      phase HPLC. Pseudo-molecular ion peaks corresponding to Gln-Ile-Ser(p)-Val-Arg
      (MW 681.7) and Glu-Ala-Thr-Ser(p)-Gln-Glu-Leu (MW 856.8) were detected from the
      tryptic digest of RPa and chymotryptic digest of PSP, respectively, which agreed
      with the theoretically expected phosphopeptide fragments.

PMID- 15171296
TI  - Development of a headspace GC/MS analysis for carbonyl compounds (aldehydes and
      ketones) in household products after derivatization with o-(2,3,4,5,6
      pentafluorobenzyl)hydroxylamine.
AB  - Carbonyl compounds (aldehydes and ketones) are suspected to be among the chemical
      compounds responsible for Sick Building Syndrome and Multiple Chemical
      Sensitivities. A headspace gas chromatography/mass spectrometry (GC/MS) analysis
      for these compounds was developed using derivatization of the compounds into
      volatile derivatives with o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBOA).
      For GC/MS detection, two ionization modes including electron impact ionization
      (EI) and negative chemical ionization (NCI) were compared. The NCI mode seemed to
      be better because of its higher selectivity and sensitivity. This headspace GC/MS
      (NCI mode) was employed as analysis for aldehydes and ketones in materials (fiber
      products, adhesives, and printed materials). Formaldehyde was detected in the
      range of N.D. (not detected) to 39 microg/g; acetaldehyde, N.D. to 4.1 microg/g;
      propionaldehyde, N.D. to 1.0 microg/g; n-butyraldehyde, N.D. to 0.10 microg/g;
      and acetone, N.D. to 3.1 microg/g in the samples analyzed.

PMID- 15171297
TI  - Chemometric techniques on inorganic elements composition for the determination of
      the geographic origin of Welsh onions.
AB  - Techniques to determine the producing country of Welsh onions (Allium fistulosum
      L.) were developed by using 216 samples from Japan and from Anchu Shandgon,
      Shanghai and Amoy Fjian in China. Twelve elements (Na, P, K, Ca, Mg. Mn, Fe, Cu,
      Zn, Sr, Ba, Al, Co, Ni, Rb, Mo, Cd, Cs, La, Ce, Tl and Pb) contained in Welsh
      onions were determined. In order to determining whether Welsh onions originate in
      Japan or in China, linear discriminant analysis (LDA) and soft independent
      modeling of class analogy (SIMCA) were performed, using concentrations of 20
      elements excluding Al and Pb in 22 elements. In LDA for two-group discrimination
      modeled on Welsh onions from Japan and China, 103 samples used for modeling were
      classified 95% correctly, and 89 other samples were predicted 94% correctly. As
      the average of predictions by SIMCA modeled on samples selected by 10 times of
      random selections, 192 samples, including the 103 samples used for modeling, were
      predicted 96% correctly. In discriminations by combined LDA and SIMCA, all 81
      samples produced in Japan were correctly judged to be Japanese ones, and only 8
      samples out of 111 samples produced in China were not correctly judged to be
      Chinese ones.

PMID- 15171298
TI  - Simultaneous determination of aniline and cyclohexylamine by principal component
      artificial neural networks.
AB  - A specterophotometric method for simultaneous determination of aniline and
      cyclohexylamine using principal component artificial neural networks is proposed.
      This method is based on the reactions involving aniline and/or cyclohexylamine,
      with bis(acetylacetoneethylendiamine)tributylphosphine cobalt(III) perchlorate as
      a complexing reagent. A nonionic surfactant, Triton X-100, was used for
      dissolving the complexes and intensifying the signals. The absorption data were
      based on the spectra registered in the range of 350 - 550 nm. An artificial
      neural network consisting of three layers of nodes was trained by applying a back
      propagation learning rule. Sigmoid transfer functions were used in the hidden and
      output layers to facilitate nonlinear calibration. The predictive ability of
      artificial neural networks was examined for the determination of aniline and
      cyclohexylamine in synthetic mixtures.

PMID- 15171299
TI  - Kinetic determination of silver ion by its perturbation on Belousov-Zhabotinskii
      oscillating chemical reaction using potentiometric method.
AB  - Silver ion can perturb the Belousov-Zhabotinskii (B-Z) oscillating chemical
      reaction. Therefore, the B-Z oscillating system was applied in the determination
      of silver ion by using a platinum wire as an indicator electrode in the
      potentiometric method. The amplitude of the potentiometric oscillation increased
      linearly in proportion to [Ag+] in the range of 9.42 x 10(-6) M to 2.54 x 10(-4)
      M, with a correlation coefficient of 0.999 under the optimum conditions. The
      obtained LOD (2sigma) was 8.85 x 10(-6) M and the relative standard deviation
      (RSD) for five measurements of 1 x 10(-4) M silver ion was 5%. The influence of
      some potentially interference was also investigated.

PMID- 15171300
TI  - Cervical precancer and cancer, past, present and future.
AB  - This review is a short summary of the very long history of invasive and in situ
      carcinomas of the cervix. The items considered in this paper are the etiology of
      cervical cancer by a sexually transmitted agent proposed about 150 years ago by
      Domenico Rigoni Stern, the birth of radical surgery for the treatment of cervical
      invasive carcinoma with the Wertheim operation in 1898, radium therapy and
      chemotherapy, cytological diagnosis, the birth of colposcopy, microcolposcopy,
      the definition of carcinoma in situ, dysplasia and microcarcinoma, the birth of
      the International Federation for Cervical Pathology and Colposcopy,
      condylomatosis lesions of the cervix and some HPVs as agents of cervical pre
      cancer and cancer, and finally the concept of vaccination against oncogenic HPV
      types. All these constitute an integral part of common medical practice.

PMID- 15171302
TI  - Successful vaccine immunotherapy. An exciting novel approach to cancer treatment.
AB  - Global cancer spread to pandemic proportions, has reinforced the importance of
      disease surveillance and prevention programs, and has provided the stimulus for
      greater resources in vaccine development. Many reports from phase I or II trials
      indicate that both partial and complete responses have been observed, with little
      or no toxicity, in a small proportion of vaccine recipients. Future prospects
      will be to increase basic knowledge of immunogenic tumor antigens to vaccine
      administration, which will make the cancer patient develop an immune response
      able to induce tumor regression. Clinical trials already under way in patients
      with malignant diseases may yield more definitive conclusions.

PMID- 15171301
TI  - Prognostic and therapeutic importance of lymphadenectomy in gynecological
      cancers.
AB  - Lymphadenectomy has been a matter of interest for years because of the increased
      morbidity rates in gynecological cancers due to the procedure itself and because
      the procedure requires experience. Although a number of alternative methods have
      been developed to find out the prevalence of gynecological cancers, dissection
      and histopathological evaluation of lymph nodes is still the gold standard in
      detecting disease. Even though there are opposing views regarding this approach,
      since the morbidity rate has decreased over the years many studies in the
      literature report that lymphadenectomy has prognostic and therapeutic value. Its
      contribution to survival can be attributed both to its being determinant in
      postoperative treatment modifications and to debulking and lymphadenectomy
      itself. In order to reap the prognostic and therapeutic benefit expected from
      lymphadenectomy, a sufficient number of lymph nodes must be dissected. Surgical
      experience is important both for the procedure itself and to reduce the morbidity
      due to the procedure. This study discusses the prognostic and therapeutic
      importance of lymphadenectomy in ovarian, endometrial, cervical and vulvar
      cancers.

PMID- 15171303
TI  - Carcinoma in situ and early breast carcinoma. Survey of the Portuguese Senology
      Society on the diagnostic tools used in Portugal and their evolution between 1985
      and 2000.
AB  - By means of a questionnaire, sent to the Portuguese hospitals which diagnose and
      treat most female patients with breast cancer, it was intended to assess the
      situation regarding the diagnosis of carcinoma in situ and early breast cancer
      (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The
      hospital participation rate was 65% and a sample of 865 patients was collected,
      distributed in the years 1985, 1990, 1995 and 2000. It was found that the
      presentation form of breast cancer in 1985 was of palpable tumour in 87% of the
      cases, whereas in 2000 this situation only corresponded to 54% of the patients,
      being most of the remaining patients diagnosed by imaging without palpable
      tumour. In 94% of the patients, the first diagnostic investigation was
      mammography, associated or not to echography, and the second most frequent
      investigation was fine-needle aspiration biopsy. The time evolution of the tumour
      size showed an increasingly earlier diagnosis. Invasive tumours not more than 1
      cm represented 13.2% in 1985 and 20.3% in 2000. On the other hand, breast cancers
      more than 2 cm and not more than 5 cm decreased from 67.2% in 1985 to 40% in
      2000. When oncology centres and some large university hospitals (Group A) were
      compared to the other hospitals (Group B), there were no significant differences
      between the diagnostic methods, although the sequence of diagnostic methods was
      different in the hospitals in Group A versus those in Group B. It was observed
      that in more differentiated hospitals the diagnosis was achieved increasingly
      earlier along the studied periods, and this situation did not occur in the other
      hospitals.

PMID- 15171305
TI  - Clinicopathologic outcomes of laser conization for high-grade cervical dysplasia.
AB  - PURPOSE OF INVESTIGATION: To evaluate the incidence of thermal artifact and rates
      of persistent disease and recurrence in laser conization for cervical dysplasia.
      METHODS: A retrospective study examined the cases of 110 patients who underwent
      carbon dioxide laser conization for high-grade cervical dysplasia at our
      institution between January 1999 and March 2002. Rates of thermal artifact,
      persistent disease, recurrence, hemorrhage and cervical stenosis were
      investigated. Dysplasia severity and recurrence rates in smokers were also
      evaluated. RESULTS: One hundred and five (95.5%) of 110 laser cones had negative
      margins, and only five (4.5%) had significant thermal artifact, with two (1.8%)
      noted to interfere with adequate evaluation of margins. Seventy-eight patients
      returned to Roswell Park Cancer Institute (RPCI) for follow-up with a mean follow
      up period of 15.7 months. Fourteen (12.7%) patients had persistent disease
      detected within two visits, and one (0.9%) patient had a recurrence of dysplasia
      at ten months. One (0.9%) patient had same-day postoperative hemorrhage requiring
      hemostatic suturing. There were no cases of cervical stenosis detected at follow
      up. Smokers had an increased incidence of high-grade lesions on cone biopsy when
      compared to non-smokers (46/57 and 30/53 patients, 80.7% and 56.7%, respectively;
      p = 0.008). The rate of persistent disease or recurrence was 8/57 (14%) in
      smokers and 7/53 (13.2%) in non-smokers (p = not significant). CONCLUSION: Laser
      conization is an efficacious and safe procedure for the treatment of high-grade
      cervical dysplasia, with a very low incidence of thermal artifact and
      postoperative complications, and a relatively low rate of persistent disease.
      Smokers had a significantly increased incidence of high-grade lesions on cone
      biopsy.

PMID- 15171304
TI  - Establishment and characterization of two different types of new human
      endometrial adenocarcinoma cell lines (HEC-251 and HEC-265).
AB  - OBJECTIVE: Endometrial carcinomas are grouped into two types of carcinogenic
      entities. These two different types of cell lines designated as HEC-251 and HEC
      265 were established from human endometrial adenocarcinoma. We report their
      characteristics. MATERIALS: HEC-251 was derived from moderately differentiated
      endometrioid adenocarcinoma and HEC-265 from well-differentiated adenocarcinoma.
      RESULTS: These cell lines grow well and serial passages can be successively
      carried out more than 100 times. The monolayer cultured cells reveal neoplastic
      and pleomorphic features, and grow in multilayers. HEC-251 cells are immuno
      cytochemically positive for p53 and HEC-265 cells for PgR. Both cell lines are
      transplantable to nude mice and reflect the original histopathologic
      characteristics. CONCLUSION: The cell lines HEC-251 and HEC-265 will contribute
      to clarifying the characteristics of two different types of human endometrial
      carcinomas.

PMID- 15171306
TI  - Pathological characteristics of ovarian cancer occurring after hysterectomy.
AB  - OBJECTIVE: The aim of the current study was to examine the pathological
      characteristics of ovarian cancer occurring in women with previous hysterectomy.
      METHODS: Newly diagnosed cases of ovarian primary epithelial or primary
      peritoneal cancer, operated on in our department between January 2000 and
      December 2002, were included in this retrospective study. The patients were
      divided into two groups, group I included eight patients with ovarian cancer and
      previous hysterectomy, and group II comprised 70 patients with ovarian or primary
      peritoneal cancer, but without previous hysterectomy. RESULTS: There was no
      significant difference between the eight patients with ovarian cancer and
      previous hysterectomy and the 70 patients without previous hysterectomy
      considering the patients' characteristics. Conversely, there was a difference
      between the two study groups regarding the histology of the tumor, its grade and
      the stage of the disease. All patients with ovarian cancer and previous
      hysterectomy had poorly differentiated mixed epithelial or undifferentiated
      tumors. Nevertheless, only 25% of these patients were diagnosed in Stage IIIC.
      CONCLUSION: It seems that besides reducing the risk of further ovarian cancer,
      hysterectomy also causes a change in the main histological sub-group of ovarian
      cancer, that develops in patients with previous hysterectomy. The greatest
      protective effect was observed for serous ovarian tumors.

PMID- 15171308
TI  - Clinical review of 55 cases of malignant ovarian germ cell tumors.
AB  - PURPOSE OF INVESTIGATION: A retrospective analysis of 55 cases of malignant germ
      cell tumors in a 20-year period was done to evaluate the impact of conservative
      surgery and adjuvant treatment on survival and fertility. METHODS: Fifty-five
      cases of malignant ovarian germ cell tumors (MOGCTs) were studied. Mean age was
      22 years. Dysgerminoma was the most common histotype (45%). RESULTS: Thirty-nine
      patients (71%) presented with FIGO surgical Stage I disease. Fertility-sparing
      surgery was performed in 39 (71%) women. Postoperative systemic chemotherapy was
      administered to 40 women (73%), 27 (68%) had received conservative treatment. One
      woman developed renal failure after the first cycle of chemotherapy and died a
      few days thereafter and there was one case of bleomycin-induced death due to
      pulmonary fibrosis. There were eight (14.5%) clinical recurrences. Overall
      survival rate for relapsing women was 75% (6/8). The recurrence rate for women
      treated conservatively was 15%, and it was 13% for those treated radically. With
      a median follow-up of 129 months the overall survival rate for the entire study
      population was 90.9%. Eleven pregnancies occurred in 36 women treated with
      fertility-sparing surgery who were of child-bearing age. CONCLUSION: The
      management of MOGCTs with fertility-sparing surgery is a safe, practicable
      treatment option. The majority of these patients can retain normal ovarian
      function and reproductive potential after chemotherapy treatment.

PMID- 15171307
TI  - Soybean isoflavones inhibit estrogen-stimulated gene expression in mouse uteri.
AB  - This study was performed to examine the inhibitory effects of soybean isoflavones
      on estrogen-stimulated gene expression of the uteri in ovarectomized mice.
      Especially when compared with the inhibitory effect of genistein and daidzein as
      aglycosides described in our previous report, subcutaneous administration of the
      glycoside genistin significantly decreased the levels of estradiol-17beta (E2)
      induced expressions of c-jun, interleukin (IL)-1alpha and tumor necrosis factor
      (TNF)-alpha mRNAs (p < 0.005, p < 0.05 and p < 0.05, respectively) and seemingly
      proteins in the mice uteri, whereas the glycoside daidzin weakly inhibited E2
      stimulated expressions of c-fos and IL-1alpha. Both genistin and daidzin seemed
      to have a weaker inhibitory effect than that of genistein and daidzein on the
      expression of estrogen-stimulated genes. It is suggested that those glycosides
      are naturally derived and generally absorbed from plant foods and might prevent
      E2-related endometrial carcinogenesis.

PMID- 15171309
TI  - Modification of ultrasonographically measured endometrial thickness after
      discontinuation of adjuvant therapy with tamoxifen in postmenopausal breast
      cancer patients.
AB  - INTRODUCTION: The aim of this study was to evaluate endometrial changes after
      five years of tamoxifen treatment by measuring endometrial thickness with
      transvaginal ultrasonography. MATERIALS AND METHODS: Fifty-five asymptomatic
      postmenopausal women who had assumed tamoxifen, 20 mg daily, for five years were
      controlled six months after discontinuation of the therapy. Of these 42 were
      followed-up at 12 months. Statistical analysis was performed using the analysis
      of variance for repeated measures and the Anova test; p < 0.05 was considered
      statistically significant. RESULTS: We found a significant reduction in
      endometrial thickness at six months (p = 0.0046) and at 12 months (p = 0.0003)
      but not between six and 12 months (p = 0.06). CONCLUSION: A statistically
      significant reduction in endometrial thickness after discontinuation of tamoxifen
      therapy was found. This can probably be attributed to the cessation of the
      estrogenic side-effects of tamoxifen therapy.

PMID- 15171312
TI  - Role of plasma nitric oxide in complete hydatidiform mole.
AB  - PURPOSE OF INVESTIGATION: This prospective study aimed to evaluate any
      relationship between development of complete hydatidiform mole and plasma levels
      of nitric oxide (a biologically active mediator derived from L-arginine), and
      human chorionic gonadotropin beta (beta-hCG; a metabolite involved in trophoblast
      production). METHODS: Levels of plasma nitric oxide and beta-hCG were measured in
      38 patients with complete hydatidiform mole pregnancies, and nitric oxide levels
      were measured in 31 women with normal pregnancies who formed the control group.
      RESULTS: For patients compared with controls, mean plasma concentrations of
      nitric oxide were significantly higher (35.84 vs 29.54 microM; p < 0.001) and
      significantly associated with increased risk of hydatidiform mole (odds ratio
      1.0105, 95% confidence interval 1.0034-1.0176). No significant relationship was
      found between plasma levels of nitric oxide and beta-hCG in the patient group.
      CONCLUSION: In patients with complete hydatidiform mole compared with controls,
      plasma nitric oxide levels were found to be significantly higher and associated
      with increased molar risk.

PMID- 15171311
TI  - First-line intraperitoneal cisplatin-paclitaxel and intravenous ifosfamide in
      Stage IIIc ovarian epithelial cancer.
AB  - OBJECTIVES: To determine the feasibility, toxicity and efficacy of a first-line
      combination of intraperitoneal (i.p.) paclitaxel and cisplatin and intravenous
      (i.v.) ifosfamide in untreated patients with Stage IIIc ovarian cancer after
      cytoreduction or biopsies only. METHODS: Twenty-six patients entered the trial
      from 1995 to 1999. Twenty underwent initial cytoreduction which was complete,
      with residual nodules < 0.5 cm or = 0.5 cm in six, five and nine patients,
      respectively. Six patients underwent biopsies only at initial surgery. Ten cycles
      of chemotherapy were planned by both routes. Second-look surgery was planned for
      all patients. RESULTS: Twenty-one (81%) of the 26 patients were in complete
      clinical remission (CCR) at the time of second-look surgery. Of the 15 patients
      who underwent second-look surgery, ten were in CCR including seven in complete
      remission (CR) confirmed pathologically. Median overall-survival had not been
      reached at 53 months (range 16-87), and median disease-free survival was 40
      months (range 8-85), for a median follow-up of 53 months (range 16-87). Local
      toxicity consisted mainly of mild abdominal pain. Systemic toxicity was
      essentially haematological, with eight (31%) grade 3-4 leukopenia. CONCLUSION:
      This study has demonstrated the feasibility, moderate toxicity and efficacy of
      first-line intraperitoneal paclitaxel-cisplatin chemotherapy.

PMID- 15171310
TI  - Clinicopathological study of vascular tumors of the breast: a series of ten
      patients with a long follow-up.
AB  - Ten cases of vascular tumors of the breast were examined in our laboratory during
      the last decade (1992-2001). Nine patients were female and one male (ages 31-77,
      average 52 years). Six patients presented parenchymal vascular lesions (1
      angiosarcoma, 1 atypical hemangioma, 3 perilobular hemangiomas, 1 cavernous
      hemangioma) measuring 0.5-6 cm in the greatest diameter. Two lesions were
      accidental findings in lumpectomy specimens excised for fibrocystic disease with
      microcalcifications. Four patients presented non-parenchymal vascular lesions:
      three cavermous hemangiomas (one in a male patient) and one angiolipoma measuring
      1-6 cm in diameter. All tumors were treated by lumpectomy with the exception of
      the atypical hemangioma which was treated by simple mastectomy. The patient with
      the angiosarcoma was treated by simple mastectomy, radiotherapy and chemotherapy
      and died with disseminated disease three years after initial diagnosis. All other
      patients are well up to date (follow-up 1-9 years).

PMID- 15171313
TI  - The significance of the degree of myometrial invasion in patients with stage IB
      endometrial cancer.
AB  - OBJECTIVE: To study the validity of the FIGO staging classification of
      endometrial cancer Stage IB by correlating degree of myometrial invasion depth
      with outcome measures. STUDY DESIGN: Fifty patients with endometrial
      adenocarcinoma FIGO Stage IB who underwent hysterectomy between 1989 and 2001
      were divided into two groups according to depth of myometrial invasion. The first
      group comprised of 31 patients with myometrial invasion of less than or equal to
      one-third. The second group included 19 patients with invasion greater than one
      third but less than one-half. The two groups were compared with regard to
      prognostic factors and outcome measures. RESULTS: The overall 5-year recurrence
      free survival, disease specific survival and overall survival rates were 87%, 94%
      and 77%, respectively. These outcome measures did not vary significantly between
      the two groups. There were no statistically significant differences between the
      two groups with regard to the following parameters: duration of follow-up, age,
      proportion of patients who underwent complete surgical staging and postoperative
      adjuvant radiotherapy. Histologic parameters of the two groups, such as
      histological type, grade and proportion of patients with capillary space-like
      involvement and lower uterine segment involvement were not significantly
      different. CONCLUSIONS: In patients with Stage IB endometrial cancer the amount
      of myometrial invasion defined as less than one third compared with invasion
      greater than one third does not appear to correlate with their outcome, thus
      validating the FIGO staging system.

PMID- 15171314
TI  - Sentinel node identification and intraoperative lymphatic mapping. First results
      of a pilot study in patients with endometrial cancer.
AB  - INTRODUCTION: To minimize the surgical morbidity after lymphadenectomy, sentinel
      node biopsy (SLNB) has become fundamental in the management of different
      malignancies. We decided to evaluate sentinel lymph node (SNL) biopsies also in
      patients with endometrial cancer undergoing hysterectomy with lymphadenectomy.
      METHODS: In the setting of a prospective study we developed a technique for
      sentinel node biopsy of ten patients with histologically confirmed endometrial
      cancer. Prior to surgery 99m Tc Nanocol was injected in the peritumoral region by
      hysteroscopy. Six hours later lymphoscintigraphy was performed to identify the
      draining lymph nodes. During surgery we first detected the sentinel lymph node by
      a hand-held gamma tracer and then removed it. Surgery was completed by the
      standard therapy of total hysterectomy, bilateral salpingo-oophorectomy and
      pelvic and/or para-aortic lymphadenectomy. RESULTS: Scintigraphic identification
      was possible in eight out of ten patients. Intraoperative identification of
      sentinel lymph nodes was possible in seven out of eight patients. In five
      patients we found the sentinel lymph nodes in the pelvic region while the other
      two patients had bilateral sentinel nodes in the pelvic and para-aortic region.
      Histologically confirmed microscopic tumor metastases of the SLNs and para-aortic
      lymph nodes were only found in one case. The sentinel lymph nodes from the other
      six patients were free of tumor and accurately reflected the pathological status.
      CONCLUSION: The identification of sentinel lymph nodes in endometrial cancer is a
      practical and safe method. In order to improve this technique as a standard
      procedure for staging of endometrial cancer further studies with a larger number
      of patients have to be done.

PMID- 15171315
TI  - Postoperative radiotherapy in stage I endometrial adenocarcinoma.
AB  - OBJECTIVE: To evaluate postoperative whole pelvic radiation for high-risk
      patients with Stage I endometrial adenocarcinoma. METHODS: One hunderd and twenty
      two patients with irregular premenopausal or postmenopausal haemorrhage were
      included into the study. Fractional curettage was performed in all cases. When
      the pathohistological report confirmed endometrial adenocarcinoma, abdominal
      hysterectomy with bilateral salpingo-oophorectomy was performed. Low-risk
      patients include women with Stage IA tumours and Stage IB grade 1 or 2 histology.
      High-risk group include patients with Stage IB grade 3 tumours and Stage IC
      carcinomas. High-risk patients received whole pelvic radiotherapy between two and
      four weeks after surgery. RESULTS: Eighty-two patients (67.21%) were low-risk and
      forty patients (32.79%) were high-risk. In the low-risk group of patients, CA-125
      was negative in ten cases and positive in 72 patients with a mean value of 30.12
      +/- 12.42 U/ml serum. In the high-risk group of the patients, CA-125 was negative
      in two cases and positive in 38 patients with a mean value of 60, 48 +/- 20, 14
      U/ml serum. Locoregional recurrences were diagnosed in four patients (4.87%) in
      the surgery group and in two patients (5.00%) assigned to radiotherapy. The
      incidence of distant metastases was 2.43% in the surgery group and 2.50% in the
      radiotherapy group. Overall survival at five years was 90.25% in the low-risk
      group and 87.50% in the high-risk group of patients. CONCLUSION: Five-year
      overall survival, locoregional and distant metastasis were similar in the low
      risk and high-risk groups of patients. That emphasizes the value of whole pelvic
      radiation in patients with unfavourable prognostic factors in Stage I endometrial
      cancer.

PMID- 15171316
TI  - A novel technique with a flexible applicator for MRI-based brachytherapy of
      cervical cancer.
AB  - PURPOSE: To introduce a novel technique for magnetic resonance (MR)-based 3
      dimensional planned high-dose rate intracervical brachytherapy (BT). MATERIALS
      AND METHODS: During 2002, 16 patients received external beam radiotherapy and BT
      as part of radiochemotherapy for cervical cancer. A special adjustable applicator
      device was designed and used for BT. The isodose distribution was calculated from
      MR images with the applicator in place. RESULTS: The planning target volume
      coverage was adequate and the radiation burden on the organs at risk was within
      acceptable limits. Complete regression was achieved in two patients (12.5%), and
      partial regression in ten (62.5%) patients. The overall response rate for the
      complex treatment was 93.75%. In three cases the disease was considered to be
      stable. CONCLUSION: The MR-compatible, flexible applicator allows safe and
      reproducible cervical radiotherapy with no added discomfort or hazard for the
      patient.

PMID- 15171317
TI  - Human chorionic gonadotropin-beta in endometrium cancer tissue.
AB  - PURPOSE: Determination of the correlation between expression of human chorionic
      gonadotropin mRNA and serum free hCGb immunoreactivity in endometrial cancer
      tissue. METHODS: The study included 56 patients with endometrial carcinoma Stages
      IB-III. The expression of mRNA hCGbeta was determined by the RT PCR method in 18
      cases of cancerous and precancerous tissues. The serum-free hCGbeta
      immunoreactivity was analyzed by sequential immunometric assay in all patients.
      RESULTS: In 15 study specimens of endometrial carcinoma tissue mRNA of hCGbeta
      was detected. Also in endometrial atypical hyperplasia, expression of hCGbeta was
      found. Noncancerous tissue demonstrated lack of the hCGbeta transcript. The serum
      immunoreactivity in the endometrial cancer group was detectable in 86% of cases.
      There were no significant differences between FIGO stages and grading.
      CONCLUSION: The results of the present study confirmed the presence of active
      genes of hCGbeta in endometrial cancer tissue, even in precancerous changes. The
      serum immunoreactivity of free hCGbeta is a less common feature and is not linked
      with tumor stage or grade in endometrial cancer patients.

PMID- 15171318
TI  - External radiation therapy for endometrial carcinoma: the University Hospital of
      Ioannina experience.
AB  - PURPOSE OF INVESTIGATION: The aim of our study was to present the experience of
      our department in the treatment of endometrial cancer with postoperative external
      beam radiotherapy (EBRT) without intracavitary brachytherapy (BRT) and to
      evaluate the efficacy of such a method. METHODS: We retrospectively retrieved the
      medical records of all patients with endometrial cancer treated with surgery and
      EBRT alone (median dose 50.0 Gy). Thirty-one women (median age: 67 years) of all
      clinical stages were reviewed and analyzed for recurrences (local or metastases)
      and late post-radiation side-effects. RESULTS: Within a median follow-up of 17
      months one patient developed local recurrence and four developed metastases.
      Overall survival was 97% and disease-free survival was 87%. Three women developed
      post-radiation colitis. No other treatment-related late side-effects were
      observed. CONCLUSION: EBRT without BRT achieved an excellent local control in
      women with endometrial cancer although some of them were candidates for
      supplementary BRT.

PMID- 15171319
TI  - DNA adducts in squamous cell cervical carcinomas associated with HPV infection.
AB  - The aim of the study was qualitative and quantitative evaluation of DNA adducts
      in squamous cell cervical carcinomas associated with oncogenic HPV infection.
      MATERIAL: The study material consisted of oncogenic tissue collected during the
      surgeries of seven women aged 37 to 52 who were undergoing surgical treatment due
      to squamous cell cervical carcinoma. The control group consisted of 3 tissue
      fragments from morphologically normal cervix collected from patients undergoing
      surgery due to uterine myomas. METHODS: DNA from the tissues was isolated using
      Genomic Prep Plus kit from A&A Biotechnology, Austria. Amplification reactions
      detecting HPV DNA presence in the tissue fragments were performed using specific
      starters allowing for amplification of conservative genome fragments within L1,
      E6 and E7 Papilloma viruses. After extraction, the DNA specimens underwent
      enzymatic digestion to nucleotides and marked on the 5' end using gamma32P-post
      labeling technique. Division and quantitative evaluation of DNA adducts was
      performed using thin-layer chromatography (TLC) on PEI-cellulose plates.
      Qualitative radioactivity measurements were performed using Bio-Imaging analyzer
      in quantitative mode. RESULTS: In all fragments, including the control, HPV 16
      and/or 18 DNA was found. Mean adduct content in cervical carcinoma tissues was
      289 adducts per 10(9) nucleotides and was higher than mean adduct content in
      control tissues (57 adducts per 10(9) nucleotides). CONCLUSIONS: The study
      results suggest that the content of DNA adducts in squamous cell cervical cancer
      associated with HPV infection may serve as a molecular marker of oncogenesis in
      this organ.

PMID- 15171320
TI  - Estrogen and progesterone expression of vessel walls with intravascular
      leiomyomatosis; discussion of histogenesis.
AB  - We report seven cases of intravenous leiomyomatosis. Growth beyond the uterus
      occurred in two of the seven cases in the broad ligament. One 21-year-old patient
      is one of the youngest reported cases in the literature. Five patients had total
      abdominal hysterectomy with removal of the adnexa and two patients underwent
      myomectomy. One of the myomectomy cases had abdominal hysterectomy and bilateral
      salpingo-oophorectomy one year later due to recurrence. The other one was disease
      free six months after the operation. Vessel walls harboring intravascular tumor
      were investigated immunohistochemically for Factor VIII, CD 34, estrogen and
      progesterone receptors with the hope of making the histogenesis of intravenous
      leiomyomatosis clear. Immunohistochemical analyses of estrogen receptors,
      progesterone receptors, vimentin, desmin, smooth muscle actin, CD 10 and h
      caldesmon were performed on intravascular tumor cells. Endothelial and
      subendothelial cells expressed none to scant, very weak progesterone and estrogen
      receptor positivity. Intravascular tumor cells showed weak (10%) to strong (70%)
      progesterone receptor positivity and weak (10%) to strong (60%) estrogen receptor
      positivity. These results do not support the hypothesis of a vessel wall origin
      for intravenous leiomyomatosis.

PMID- 15171321
TI  - Survival in primary inoperable breast cancer patients.
AB  - PURPOSE OF INVESTIGATION: Patients described as having inoperable breast cancer
      comprised a heterogeneous group of patients with variable natural history and
      survival. Over the past 20 years combined modality therapy has been used to
      improve control of disease and enhance survival. However, systemic evaluation of
      these patients has been limited and additional clinical research is needed.
      METHODS: This is a retrospective review of 136 patients with primary inoperable
      breast cancer. Twenty-five years of experience was used to examine the effect of
      several prognostic variables and different treatment modalities on survival.
      RESULTS: The median survival of inoperable breast cancer patients was 46 months
      (2 to 220). Metastatic status at initial diagnosis was an independent prognostic
      factor, while neoadjuvant chemotherapy followed by surgery seems to offer a
      survival advantage. Also, hormonal receptor status affects the long-term
      survival. CONCLUSION: Metastatic status, status of receptors and type of
      treatment provide additional prognostic information and therefore should be used
      as prognostic indicators for primary inoperable breast cancer.

PMID- 15171322
TI  - Postmenopausal endometrial cancer screening: is there a correlation between
      transvaginal sonographic measurement of endometrial thickness and body mass
      index?
AB  - OBJECTIVE: The aim of this study was to correlate the body mass index with
      transvaginal sonographic measurement of endometrial thickness in a cohort of
      postmenopausal women who were admitted for endometrial cancer surveillance.
      MATERIAL AND METHODS: Transvaginal sonographic measurement of endometrial
      thickness was performed in 97 postmenopausal women who attended the gynecology
      clinic for endometrial cancer screening with no history of hormone replacement
      therapy and correlated with body mass index. Baseline characteristics including
      age, years since menopause and body mass index were recorded for each subject.
      The relationship between transvaginal sonographic endometrial thickness and
      baseline characteristics was assessed in each. RESULTS: Body mass index was
      significantly correlated with years since menopause (r = 0.292, p = 0.004) and
      age (r = 0.243, p = 0.01) but not with endometrial thickness (r = -0.07, p =
      0.454). Endometrial thickness versus time since menopause correlation was found
      to be significant (r = 0.274, p = 0.03) in patients with a body mass index lower
      than 30. CONCLUSION: The present findings indicate that endometrial thickness
      does not differ with body mass index in the screening of postmenopausal women for
      endometrial cancer.

PMID- 15171323
TI  - Treatment delay and pathology results in women with low-grade squamous
      intraepithelial lesions. A preliminary study.
AB  - Regression rate of CIN 1 (LSIL) can reach 85%. The purpose of this study was to
      investigate retrospectively pathology specimens in CIN 1 cases who delayed
      treatment > 2 years despite the persistence of the lesion. One hundred and
      fifteen women diagnosed with CIN 1 were separated in two groups as follows: A) 92
      women who underwent ablative treatment within three months after the completion
      of two years; B) 23 women who delayed ablative treatment for a mean interval of >
      1 year after the completion of two years. Exclusion criteria were normal cytology
      and colposcopy results within the completion of two years. The chi-square, t-test
      and Kaplan-Meier method were used for analysis. Persistence of LSIL lesions was
      observed in 84% of the first group and persistence or regression of the lesion in
      78% of the second one. The study suggests the possibility of prolongation of the
      observation period after LSIL diagnosis. Prospective studies with close follow-up
      are needed for final conclusions.

PMID- 15171324
TI  - Results of cisplatin, adriamycin and etoposide chemotherapy in patients with
      recurrent and metastatic endometrial cancer.
AB  - The efficacy of the combination treatment of cisplatin, adriamycin and etoposide
      were retrospectively evaluated in 26 recurrent or metastatic endometrial cancer
      patients. One hundred and twenty-three treatment courses were observed. Patients
      received 20 mg/m2 cisplatin and 80 mg/m2 etoposide by continuous i.v. infusion
      for three days and adriamycin 40 mg/m2 i.v. the second day. Treatment courses
      were repeated every four weeks. Megestrol acetate, 160 mg/day, was added in six
      patients who had positive progesterone receptors. Ten (38.5%) women had complete
      and three (11.5%) patients had partial response with an overall response rate of
      50%. Median follow-up was 24 months. Surviving patients were alive for four
      months and six years. Toxicity was mainly hematological and gastrointestinal
      ulcerations and stomatitis were also observed.

PMID- 15171326
TI  - Primitive neuroectodermal tumor (PNET) of the uterine isthmus.
AB  - Primitive neuroectodermal tumors (PNETs) of the uterus are very rare. The
      histogenesis of these tumors is still unknown and the differential diagnosis
      includes a wide variety of tumor entities. We describe a rare case of a 68-year
      old female who presented with persistent vaginal bleeding. Physical examination
      and CT-scan revealed a large tumor in the uterus. Macroscopically the tumor
      involved the uterine isthmus. Histological and immunohistochemical examination
      showed that the tumor fulfilled the diagnostic criteria set for PNET. Only a very
      small number of cases of PNETs of the uterus have been reported in the
      literature, thus no definitive conclusions concerning the therapeutic management
      and prognosis have been ascertained.

PMID- 15171325
TI  - Recurrent extraperitoneal low grade leiomyosarcoma with unusual localization.
AB  - Primary extragenital leiomyosarcoma is rarely found in pelvic localization. A 33
      year-old multiparous woman who had recurrent low-grade leiomyosarcoma presented
      with the complaints of dyspareunia, pelvic pain and gait disturbance. Her past
      medical history revealed she had been subjected to maximal excision of a
      paravaginal mass by using vaginal and suprapubic transverse incision three years
      before. The pathology report showed that she had leiomyoma. Three years after the
      initial surgery, a paravaginal fixed mass was observed at the initial tumor bed
      and removed by the perineal approach. The histological examination of the
      specimen revealed a low grade leiomyosarcoma. She was discharged from hospital
      without any complications.

PMID- 15171327
TI  - Endometrial involvement by intra-abdominal diffuse malignant mesothelioma.
AB  - A 49-year-old patient presented with an adnexal mass. Endometrial curettage
      showed a proliferative phase and suspicious fragment resembling Arias Stella
      reaction. Laparotomy revealed an extensive nodular intra-abdominal tumor
      involving the bilateral ovaries. Microscopic findings were similar to the
      suspicious endometrial fragment in the curettage specimen. Histochemical and
      immunohistochemical studies confirmed the diagnosis of diffuse malignant
      mesothelioma with metastasis to the endometrium. This is the first reported case
      to our knowledge in the English literature.

PMID- 15171328
TI  - Microscopic endometrioid carcinoma arising in endosalpingeal endometriosis.
AB  - We present a case of microscopic adenocarcinoma arising in the right fallopian
      tube, which was incidentally found in 74-year-old woman undergoing total
      abdominal hysterectomy with salpingo-oophorectomy for uterine myoma, hematometra
      and bilateral hydrosalpinx. A small focus of endometrioid adenocarcinoma confined
      within the endosalpingeal mucosa of the right fallopian tube associated with
      endometriosis was fortuitously found during histological examination. Our case
      seems to be unique since it shows an evident filiation between the lesions of
      tubal endometriosis and an adjoining focus of microscopic carcinoma. This is the
      second case report of a microscopic endometrioid carcinoma associated with
      endosalpingeal endometriosis.

PMID- 15171329
TI  - Solitary spleen metastasis and amyloidosis in a patient with endometrial cancer.
AB  - BACKGROUND: In contrast to autopsy findings, solitary splenic metastases from
      solid tumors are extremely rare. It may occasionally be the first manifestation
      of recurrent solid cancers, and in particular of gynecologic malignancies.
      Secondary amyloidosis is also found in malignancy. CASE: A 52-year-woman
      originally diagnosed with a Stage IB, grade 2 endometrial carcinoma presented two
      and a half years later with a paroxysmal non-productive cough, weakness, loss of
      appetite and daily afternoon fever. On clinical examination wheezing on forced
      exhalation and painful splenomegaly was found. After an extensive work-up the
      patient underwent an explorative laparotomy and a splenectomy was performed.
      Histologic examination showed solitary spleen metastasis with amyloidosis. All
      symptoms resolved. As the patient had received a full course of postoperative
      irradiation after a total abdominal hysterectomy, six cycles of combination
      chemotherapy were administered. The patient remains free of recurrence, 46 months
      later. CONCLUSION: A case of solitary spleen metastasis with amyloidosis in a
      patient with endometrial cancer is presented.

PMID- 15171330
TI  - Well-differentiated papillary mesothelioma complicating endometrial carcinoma: a
      case report.
AB  - We present a case of well-differentiated papillary mesothelioma discovered during
      staging surgery for endometrial carcinoma in a 50-year-old postmenopausal woman.
      In case of simultaneous well-differentiated papillary mesothelioma (WDPM) and
      endometrial carcinoma, the surgeon may be mistaken by considering peritoneal
      implants as tumor metastasis. This situation may result in overtreatment of the
      patient. Thus a thorough pathologic examination of the specimens taking care not
      to miss any areas of invasion, and utilizing immunohistochemical analysis when
      necessary are important to avoid such mistakes. To our knowledge this is the
      first report of the simultaneous occurrence of endometrial carcinoma in
      conjunction with diffuse WDPM of the peritoneum.

PMID- 15171331
TI  - Preoperative plasma VEGF levels in ovarian masses.

PMID- 15171333
TI  - [The Hisayama Study].

PMID- 15171332
TI  - [Nippon DATA80].

PMID- 15171334
TI  - [The Ohasama Study].

PMID- 15171335
TI  - [The Suita Study].

PMID- 15171337
TI  - [Vascular remodeling].

PMID- 15171336
TI  - [Effect of mechanical stress on blood vessels].

PMID- 15171338
TI  - [Mechanism of vascular endothelial dysfunction induced by hypertension].

PMID- 15171340
TI  - [Aging and senescence in the development of hypertensive target-organ damage].

PMID- 15171339
TI  - [Oxidative stress and vascular dysfunction in hypertension].

PMID- 15171341
TI  - [Gender difference as a risk factor for the development of hypertensive organ
      damage].

PMID- 15171342
TI  - [Salt intake as a risk factor in the development of hypertensive organ damage].

PMID- 15171343
TI  - [Calcium, magnesium and potassium intake in hypertension].

PMID- 15171344
TI  - [Alcohol consumption as a risk factor in the development of hypertension].

PMID- 15171345
TI  - [Smoking habits as a risk factor in the development of hypertensive organ
      damage].

PMID- 15171346
TI  - [Exercise therapy for patients with hypertension].

PMID- 15171347
TI  - [Obesity as a risk factor in the development of hypertensive organ damage].

PMID- 15171348
TI  - [Gene mutation and polymorphism as risk factors in the development of
      hypertensive organ damage].

PMID- 15171349
TI  - [Human angiotensinogen gene and its implication in essential hypertension].

PMID- 15171350
TI  - [ACE gene polymorphism as a risk factor in the development of hypertensive organ
      damage].

PMID- 15171351
TI  - [Alpha-adducin gene and hypertension].

PMID- 15171352
TI  - [Klotho gene and hypertension].

PMID- 15171353
TI  - [Gene polymorphisms of angiotensin II-type 1 receptor in hypertension].

PMID- 15171354
TI  - [Beta3-adrenergic receptor gene polymorphism as a risk factor in the development
      of hypertensive organ damage].

PMID- 15171355
TI  - [Polymorphism in guanine nucleotide-binding protein (G-protein) beta 3 subunit
      (GNB3) gene as a risk factor in the development of hypertensive organ damage].

PMID- 15171356
TI  - [Hypertension and the target organ damage--involvement of sympathetic nervous
      system activity].

PMID- 15171357
TI  - [Involvement of angiotensin II in pathogenesis of hypertension and target organ
      damage].

PMID- 15171358
TI  - [Involvement of Aldosterone and mineralocorticoid receptor in pathogenesis of
      cardiovascular diseases].

PMID- 15171359
TI  - [involvement of chymase in pathogenesis of cardiovascular diseases].

PMID- 15171361
TI  - [Involvement of catecholamine receptors in the pathogenesis of hypertension and
      hypertensive target-organ damage].

PMID- 15171360
TI  - [Involvement of calcium channels in the pathogenesis of hypertension].

PMID- 15171363
TI  - [Involvement of endothelin in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171362
TI  - [Involvement of dopamine receptor in the pathogenesis of hypertension and
      hypertensive target-organ damage].

PMID- 15171364
TI  - [Involvement of ouabain (digitalis-like factor) in the pathogenesis of
      hypertension and hypertensive target-organ damage].

PMID- 15171365
TI  - [CO-mediated regulation of vascular function and hypertensive disorders].

PMID- 15171366
TI  - [Involvement of PPARgamma in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171367
TI  - [Involvement of TNF-alpha in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171368
TI  - [Involvement of HGF in the pathogenesis of hypertension and hypertensive target
      organ damage].

PMID- 15171369
TI  - [Involvement of small GTPase Rho and Rho-kinase in the pathogenesis of
      hypertension and hypertensive target organ damage].

PMID- 15171370
TI  - [Involvement of Insulin resistance in the pathogenesis of hypertensive target
      organ damage].

PMID- 15171371
TI  - [Involvement of homocysteine in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171372
TI  - [Involvement of leptin in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171373
TI  - [Involvement of adiponectin in the pathogenesis of hypertension and hypertensive
      target-organ damage].

PMID- 15171374
TI  - [Kallikrein-kinin in hypertension].

PMID- 15171375
TI  - [Involvement of prostanoid receptors in hypertension and hypertensive target
      organ damage].

PMID- 15171376
TI  - [Adrenomedullin and hypertension].

PMID- 15171377
TI  - [NO and hypertension].

PMID- 15171378
TI  - [Pulse pressure in the diagnosis of arteriosclerosis].

PMID- 15171379
TI  - [Pulse wave velocity in the diagnosis of arteriosclerosis].

PMID- 15171380
TI  - [Diagnostic test of pulse wave analysis: augmentation index (AI) for
      arteriosclerosis].

PMID- 15171381
TI  - [Ultrasonographic measurement of intima-media thickness in the diagnosis of
      arteriosclerosis].

PMID- 15171382
TI  - [Plaque score in the diagnosis of arteriosclerosis].

PMID- 15171383
TI  - [Assessment of carotid arterial distensibility using beta stiffness index in the
      diagnosis of arteriosclerosis].

PMID- 15171384
TI  - [Integrated backscatter for diagnosis of arteriosclerosis].

PMID- 15171385
TI  - [Evaluation of the calcification of the coronary artery using electron beam CT].

PMID- 15171386
TI  - [High sensitivity C-reactive protein analysis in th diagnosis of
      arteriosclerosis].

PMID- 15171387
TI  - [Electrocardiographic findings in hypertension].

PMID- 15171388
TI  - [Echocardiographic examination in patients with hypertension].

PMID- 15171389
TI  - [Quantification of left ventricular hypertrophy].

PMID- 15171390
TI  - [Natriuretic hormones as biomarkers for hypertension and hypertensive
      complications].

PMID- 15171392
TI  - [Clinical significance of funduscopy in diagnosis of retinopathy in patients with
      hypertension].

PMID- 15171391
TI  - [Evaluation of renal function in hypertensive patients].

PMID- 15171393
TI  - [Cardiovascular events due to hypertension].

PMID- 15171394
TI  - [Angina pectoris in hypertensive patients].

PMID- 15171396
TI  - [High blood pressure and cardiac hypertrophy].

PMID- 15171395
TI  - [Myocardial infarction in patients with hypertension].

PMID- 15171397
TI  - [Heart failure in patients with hypertension].

PMID- 15171398
TI  - [Epidemiology of hypertensive kidney failure].

PMID- 15171399
TI  - [Hypertensive nephrosclerosis].

PMID- 15171400
TI  - [Hypertensive cerebral hemorrhage].

PMID- 15171401
TI  - [Hypertension as a risk factor for cerebral infarction].

PMID- 15171402
TI  - [Hypertension as a risk factor for asymptomatic cerebrovascular disease].

PMID- 15171403
TI  - [Hypertension as a risk factor for cognitive disorders and dementia].

PMID- 15171404
TI  - [Hypertensive retinopathy].

PMID- 15171405
TI  - [Control of blood pressure in prevention of hypertensive end-organ damage].

PMID- 15171406
TI  - [Hypertension in the elderly].

PMID- 15171407
TI  - [Pediatric and adolescent hypertension].

PMID- 15171409
TI  - [Nocturnal blood pressure (dipper, non-dipper)].

PMID- 15171408
TI  - [Ambulatory blood pressure monitoring and self-measurement of blood pressure at
      home].

PMID- 15171410
TI  - [Morning hypertension].

PMID- 15171411
TI  - [White coat hypertension].

PMID- 15171412
TI  - [Hypertension in pregnancy].

PMID- 15171413
TI  - [Malignant hypertension].

PMID- 15171414
TI  - [Hypotension].

PMID- 15171415
TI  - [Treatment of hypertension in diabetics].

PMID- 15171416
TI  - [Management of hypertension in patients with cerebrovascular disease].

PMID- 15171417
TI  - [Hypertension in patients with ischemic heart disease].

PMID- 15171418
TI  - [Hypertension in patients with cardiac hypertrophy].

PMID- 15171419
TI  - [Hypertension in patients with heart failure].

PMID- 15171420
TI  - [Hypertension in obesity].

PMID- 15171421
TI  - [Sleep apnea syndrome and hypertension].

PMID- 15171422
TI  - [Hyperuricemia in hypertension].

PMID- 15171423
TI  - [Renovascular hypertension].

PMID- 15171424
TI  - [Renal parenchymal disease and hypertension].

PMID- 15171425
TI  - [Hypertension in acromegaly].

PMID- 15171426
TI  - [Hypertension associated with hyperthyroidism and hypothyroidism].

PMID- 15171427
TI  - [Hypertension secondary to hyperparathyroidism].

PMID- 15171428
TI  - [Hypertension secondary to primary aldosteronism].

PMID- 15171429
TI  - [Hypertension secondary to Cushing syndrome].

PMID- 15171430
TI  - [Hypertension secondary to adrenal steroidogenic enzyme deficiency].

PMID- 15171431
TI  - [Hypertension secondary to pheochromocytoma].

PMID- 15171432
TI  - [CNS and neurogenic hypertension].

PMID- 15171433
TI  - [Drug-induced hypertension].

PMID- 15171434
TI  - [Organ protection by antihypertensive measures].

PMID- 15171435
TI  - [Calcium channel blocker for protection against hypertensive target-organ
      damage].

PMID- 15171436
TI  - [ACE inhibitors for protection against hypertensive target-organ damage].

PMID- 15171437
TI  - [Organ protection by angiotensin II receptor blockers].

PMID- 15171438
TI  - [Diuretics for protection against hypertensive target-organ damage].

PMID- 15171439
TI  - [Alpha blocker for protection against hypertensive target-organ damage].

PMID- 15171440
TI  - [Beta-blockers for protection against hypertensive target-organ damage].

PMID- 15171441
TI  - [Protective effect of alpha beta-blockers on hypertensive target-organ damage].

PMID- 15171442
TI  - [Centrally-acting antihypertensive drugs].

PMID- 15171443
TI  - [Combination drug therapy in hypertension].

PMID- 15171444
TI  - [Management of hypertensive patients with cardiovascular damage].

PMID- 15171446
TI  - [Clinical trials on protective efficacy of antihypertensive agents for organ
      damage due to diabetes mellitus complicated with hypertension].

PMID- 15171445
TI  - [Protective effect of antihypertensive agents on renal insufficiency (REIN,
      RENAAL, IDNT, AASK, etc)].

PMID- 15171447
TI  - [Clinical trials on protective efficacy of statins for cardiovascular events due
      to hyperlipidemia (J-LIT, 4S, CARE, LIPID etc)].

PMID- 15171448
TI  - [Future aspects of the Japanese guidelines for the management of hypertension].

PMID- 15171449
TI  - [Scope].

PMID- 15171450
TI  - [ALLHAT trial--antithesis to the overuse of vasodilating antihypertensive drugs].

PMID- 15171451
TI  - [Renal protective action of T-, L-, and N-type Ca channel blockers].

PMID- 15171452
TI  - [Development of combined drugs (ARB and diuretics)].

PMID- 15171453
TI  - [Usefulness of 201Tl SPECT in the predication of mediastinal lymph nodes
      metastasis in patients with non small cell lung carcinoma (NSCLC)].
AB  - Predictivity of mediastinal lymph nodes metastasis of 201Tl SPECT were examined
      before operation in 113 patients with non-small cell lung cancer (69
      adenocarcinoma, 31 squamous cell carcinoma, 10 large cell carcinoma, 2 bronchiolo
      alveolar carcinoma, 1 neuroendocrine cell carcinoma). Patients were classified
      into two groups, with or without lymph nodes metastasis according to the
      pathological diagnosis. We calculated parameters of 201Tl SPECT early ratio,
      delayed ratio, retention index (RI) and maximal diameters. In addition, we
      calculated optimal cut-off value of RI to estimate the mediastinal lymph nodes
      metastasis. Mediastinal lymph nodes metastasis was confirmed pathologically in 62
      patients. ER and DR did not show any statistical significance between two groups.
      Maximal diameters of primary tumor were also comparable between two groups. RI
      was significantly higher in mediastinal lymph node metastasis positive group
      compared to that in mediastinal lymph node metastasis negative group. The
      sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative
      predictive value (NPV) and accuracy (Acc) of 201Tl SPECT were 82.2%, 82.3%,
      85.0%, 79.2% and 82.3%. These parameters were similar of higher than 72.6%,
      82.4%, 83.3%, 71.2% and 77.0% of chest CT. The RI of 201Tl SPECT was useful tool
      for predicting lymph nodes metastasis in non-small cell lung cancer. The optimum
      cut-off value of RI in the prediction of mediastinal lymph nodes metastasis was
      35%. We should take into account of upstaging in cases with higher RI (>35%).

PMID- 15171454
TI  - [Comparison between unstable angina pectoris and stable effort angina pectoris by
      using 123I-BMIPP and 201Tl myocardial SPECT].
AB  - We performed BMIPP myocardial SPECT and Tl myocardial SPECT in patients with
      unstable angina (UAP) and stable effort angina (SAP), and compared the results
      for the two groups. Our subjects were 30 patients with the UAP and 25 patients
      with the SAP. The early and delayed images of the BMIPP were obtained with
      patients at rest. The early image of the Tl alone was obtained with patients at
      rest. We calculated severity score (SS) using the polar map based on SPECT short
      axis image on the both myocardial SPECT. And, we calculated % uptake of the
      responsible coronary lesion and regional washout rate (WR) on myocardial SPECT
      with BMIPP. On coronary angiogram, no difference in % diameter stenosis was seen
      between the two groups. On myocardial SPECT with Tl, no difference in the SS was
      seen between the two groups. However, on myocardial SPECT with BMIPP, the SS was
      significantly higher score in the UAP group than in the SAP group. And, on
      myocardial SPECT with BMIPP, the % uptake and the WR were significant lower
      values in the UAP group than in the SAP group. Even if the two groups have almost
      the same level of myocardial perfusion disorder, the UAP group may have severer
      myocardial fatty-acid metabolic disorder than the SAP group, because the defects
      in BMIPP were significantly severer in the UAP group.

PMID- 15171455
TI  - [Development of method to estimate delay time for arterial imput function with
      [15O]CO2-PET study using sinogram data and attenuation map].
AB  - The difference in tracer arrival times between the external radiation detector
      and the brain following administration of radioactivity (delay time) must be
      estimated correctly in order to quantitatively measure regional cerebral blood
      flow (rCBF) with positron emission tomography and [15O]H2O by autoradiographic
      method. Instead of intervenous injection of [15O]H2O, bolus inhalation of
      [15O]CO2 gas is sometimes used to simplify the measurement of rCBF. In the case
      of [15O]CO2, radioactive gas in mask and nasal cavity contributes large artifact
      on the sinogram data and it is difficult to estimate delay time from the sinogram
      data. In this paper, we proposed a new method to estimate the delay time using
      the sinogram data and the attenuation map (attenuation weighted sinogram method).
      In the present method, the attenuation map was used to eliminate the effect of
      the gas outside the brain region from the sinogram data. For the validation of
      the present method, PET data with [15O]CO2 (n = 10) were analyzed. Three methods,
      namely the image method, the sinogram method and the attenuation weighted
      sinogram method were used to estimate the delay time. The estimated delay times
      and calculated rCBF images by three methods were compared. Due to the
      radioactivity outside of the brain, the sinogram method significantly
      overestimated the delay time and thus underestimated the rCBF value compared with
      the image base method. On the other hand, there were good agreements between the
      delay times estimated by the attenuation weighted sinogram method and the image
      method. The present method can eliminate the effect of the radioactivity outside
      of the brain on the sinogram data and estimate the delay time accurately and fast
      enough for clinical use.

PMID- 15171457
TI  - [The 25th report on survey of the adverse reaction to radiopharmaceuticals (the
      28th survey in 2002)].

PMID- 15171456
TI  - [Examination of occupational exposure to medical staff (primarily nurses) during
      131I medical treatments].
AB  - Recently, a new amendment to protect against radiation damage to humans has been
      enacted based on a 1990 recommendation by the ICRP. Consequently, the dose limits
      of occupational exposure to medical staff were cut down sharply compared with
      conventional readjustments. This amended bill, however, may be triggering a
      reduction in the number of applicants, which hope to engage in radiotherapy. This
      being the case, we measured the dose levels of the occupational exposure to
      medical staff (doctor's group, nuclear medicine technologist's group, nurse's
      group and pharmacist's group) from 1999 to 2002. Moreover, we investigated what
      the main factor is in nurse's occupational exposure to 131I. The highest doses of
      occupational exposure were 3.640 mSv to doctors, 7.060 mSv to nuclear medicine
      technologists, 1.486 mSv to nurses and 0.552 mSv to pharmacists. According to our
      results, it was clear that the highest doses in each group were far below the
      legally mandated upper limits of exposure doses. Although we investigated the
      correlations between the factors of nurse's occupational exposure to 131I with
      the number of inpatients, the amount of 131I and the number of servicing times
      for patients, there were no correlations found. Furthermore, to analyzing the
      factors in detail, it became clear that the main factor in the nurse's
      occupational exposure was due to the existence of patients who needed many more
      servicing times for their care than ordinary patients.

PMID- 15171458
TI  - [Drawing up the guidelines for ventilation, draining and disposal of radioactive
      medical waste].

PMID- 15171459
TI  - Assessing underreporting response bias on the MMPI-2.
AB  - The authors assess the replicability of the two-factor model of underreporting
      response style. They then examine the relative performance of scales measuring
      these styles in analog (ARD) and differential prevalence group (DPG) designs.
      Principal components analysis produced a two-factor structure corresponding to
      self-deceptive (SD) and impression management (IM) response styles. The IM factor
      scale and related individual validity scales were elevated among research
      participants instructed to fake good on the MMPI-2 as compared with participants
      who completed the MMPI-2 under standard instructions (ARD) and among individuals
      evaluated in real-life assessment contexts where underreporting is expected
      (DPG). Participants in DPG samples produced significantly higher SD factor and
      related individual scale scores than did the ARD participants instructed to fake
      good. These findings confirm that the MMPI-2 validity scales measure two types of
      underreporting styles and that these styles may operate differently in ARD versus
      DPG designs.

PMID- 15171461
TI  - Discriminating malingered from genuine civilian posttraumatic stress disorder: a
      validation of three MMPI-2 Infrequency scales (F, Fp, and Fptsd).
AB  - The Infrequency-Posttraumatic Stress Disorder scale (Fptsd), recently created for
      the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), has demonstrated
      incremental validity over other MMPI-2 scales in malingered posttraumatic stress
      disorder (PTSD) detection. Fptsd was developed with combat-exposed PTSD patients,
      potentially limiting its use with PTSD patients in general. The current study
      evaluated the MMPI-2's F, Infrequency-Psychopathology scale (Fp), and Fptsd
      scales in discriminating genuine civilian PTSD among 41 adult victims of child
      sexual abuse from a group of 39 students instructed to simulate PTSD. Analyses
      demonstrated Fptsd's incremental validity over F but not over Fp. Based on the
      two studies examining Fptsd, Fptsd may be more appropriate for combat trauma
      victims, and Fp may be more appropriate for civilian trauma victims.

PMID- 15171460
TI  - Five-factor model prototypes for personality disorders: the utility of self
      reports and observer ratings.
AB  - The current study examined the prototype-matching technique for using the five
      factor model (FFM) of personality to assess personality disorders (PDs) and their
      correlates. The sample was composed of 69 psychiatric patients, most of whom
      suffered from affective or anxiety disorders. The participants were predominantly
      outpatients (78%), Caucasian (94%), and women (58%). NEO Personality Inventory
      (NEO-PI) data from these patients and informants were available for deriving PD
      prototype scores. The results supported four conclusions. First, the FFM
      prototype-matching method is useful for clinical samples. Second, agreement
      between self-reports and information from significant others (SOs) using this
      method is good compared to previous results. Third, this agreement varies
      systematically with the observability of the PD criteria. Fourth, the value of
      self- and other-reported personality information depends on the rating source of
      the outcome variables. Other-reported information provides incremental utility in
      predicting impairment and interpersonal distress rated by clinicians and
      significant others.

PMID- 15171462
TI  - MMPI-2 F scale as a predictor of acute versus chronic disorder classification.
AB  - This study examined the relation between elevation of the infrequency (F) scale
      on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and the
      classification of psychological disorders as chronic or acute in an outpatient
      mental health setting. MMPI-2 and clinician rating data at time of intake were
      considered for 158 adult patients from an outpatient clinic. The results indicate
      that elevation on the F scale is associated with more chronic disorders even
      after the influence of other variables, such as age and comorbidity of other
      disorders, is statistically accounted for These results are discussed in terms of
      the utility and incremental validity of including the F scale as part of
      diagnostic screening.

PMID- 15171463
TI  - Cross-cultural investigation of the Questionnaire of Smoking Urges in American
      and Spanish smokers.
AB  - This study evaluated the factor structure of the Questionnaire of Smoking Urges
      (QSU) across American and Spanish smokers. Using confirmatory factor analyses,
      the fits of one-, two-, and four-factor models of smoking craving in American and
      Spanish data sets were compared. The two-factor model provided the best fit in
      both samples. However, negatively worded items confounded the interpretation of
      the two-factor structure in both the American and Spanish data. The first factor
      had positively and negatively worded items, whereas the second had only
      positively worded items. The two-factor structure was reexamined, removing either
      the positively or the negatively worded items. Using only positively worded items
      resulted in a loss of fit, whereas using only negatively worded items improved
      model fit substantially. Thus, the results supported the generalization of
      smoking craving across Spanish and American smokers and suggested that negatively
      worded items play a larger role in the two-factor structure of the QSU than
      originally thought.

PMID- 15171464
TI  - Relationship of purported measures of pathological and nonpathological
      dissociation to self-reported psychological distress and fantasy immersion.
AB  - In order to investigate both the psychometric structure of the Dissociative
      Experiences Survey (DES) and the discriminant validity of the DES-Taxon (Waller,
      Putnam, & Carlson, 1996) as a specific marker of pathological dissociation, 376
      non-clinical community based respondents completed the DES and a battery of
      psychopathology and imaginative involvement self-report measures. The DES was
      scored for both the Taxon and the DES-Absorption subscale. A DES subscale
      purported to tap normative dissociative processes. The two DES subscales
      demonstrated substantial overlap, both with each other (r = .80) and with the
      self-report measures with both DES scales comparably associated with high levels
      of psychological distress. Both DES subscales were also associated with elevated
      levels of "normative" imaginative involvement (fantasy proneness, absorption,
      daydreaming immersion). We conclude that both DES scales are largely
      indistinguishable from each other in relation to other self-report measures of
      psychopathology and fantasy access.

PMID- 15171465
TI  - Personality traits and critical thinking skills in college students: empirical
      tests of a two-factor theory.
AB  - The two-factor theory defines critical thinking skills as a combined effect of
      cognitive abilities and personality dispositions. Although the available research
      supports the association between critical thinking and measures of cognitive
      ability, the specific traits contained in the dispositional factor have not been
      clearly identified through empirical research. In Study 1,101 undergraduate
      students completed the Watson-Glaser Critical Thinking Appraisal (WGCTA), three
      subtests of the Wechsler Adult Intelligence Scale-Third Edition, and the revised
      NEO Personality Inventory. Hierarchical multiple regression analyses showed that
      Openness to Experience scores accounted for significant incremental variance in
      WGCTA scores beyond that accounted for by Similarities subtest scores. In Study
      2, similar analyses of data from 105 students also showed significant incremental
      effects for Openness to Experience, even after more variance in the cognitive
      factor was accounted for by the Verbal Comprehension Index. Implications of these
      findings for the enhancement of critical thinking skills in college students are
      discussed.

PMID- 15171466
TI  - Factor structure and differential validity of the expanded Brief Psychiatric
      Rating Scale.
AB  - The Brief Psychiatric Rating Scale (BPRS) is one of the most widely used measures
      in psychiatric outcome and clinical psychopharmacology research. To date,
      however; research on the psychometric properties of the expanded version of the
      BPRS (BPRS-E) has been limited. An exploratory factor analysis (n = 360) using
      maximum likelihood extraction with oblimin rotation found a four-factor solution
      (Thought Disturbance, Animation, Mood Disturbance, Apathy) to underlie the BPRS
      E. Furthermore, these factors were logical in nature and estimates of internal
      consistency were acceptable. A confirmatory factor analysis conducted on a
      second, independent sample (n = 280)found that for the five models currently
      available in the literature, the model developed herein provided the best fit to
      the data. Again, estimates of internal consistency were found acceptable.
      Finally, the four factors demonstrated appropriate differential validity with
      regards to both demographic variables and various psychiatric diagnoses.

PMID- 15171467
TI  - Comparison of dog and pig models for testing substernal cardiac compression
      devices.
AB  - Subtle anatomic differences between species can be a critical consideration when
      determining whether a given animal model is appropriate for surgical research
      purposes, especially when testing biomechanical implants. This study compares the
      effectiveness of two common animal models (dogs and pigs) in testing a balloon
      based cardiac compression device designed for substernal placement. Pigs were
      used in acute studies using an infarction model of heart failure, whereas dogs
      were used in chronic experiments in which heart failure was induced via rapid
      pacing. Systolic cardiac compression was accomplished in both species using
      identical balloons inflated between the sternum and right ventricle with every
      heartbeat. Results showed the device to be much more effective in pigs, where
      cardiac stroke volumes returned to normal with balloon assistance (14.7 +/- 1.9
      to 37.8 +/- 9.2 mL, p < 0.005). Stroke volumes in dogs, however, remained
      essentially unaltered by balloon activation (28.1 +/- 14.1 to 29.6 +/- 14.7 mL, p
      = NS). Retrospective comparisons showed pig models to be a much closer
      approximation to the human anatomy because of a more similar thoracic cavity
      shape and heart orientation. These findings suggest that certain large animal
      models should not be used in research in which chest wall shape or cardiac
      orientation within the thoracic cavity may influence outcomes.

PMID- 15171468
TI  - Hemocompatibility of PMEA coated oxygenators used for extracorporeal circulation
      procedures.
AB  - An inflammatory response to cardiopulmonary bypass (CPB) caused by
      bioincompatibility of extracorporeal circuits is one of the major clinical issues
      in cardiac surgery. Recently a new coating material, poly-2-methoxyethylacrylate
      (PMEA), was developed to improve the biocompatibility of blood contacting
      surfaces. In a simulated cardiopulmonary bypass model, using fresh human whole
      blood, 15 membrane oxygenators (Capiox SX18, Terumo Corp., Tokyo, Japan) were
      compared. Five of them had the PMEA coating, five had a heparin-coated surface,
      and five had no surface treatment. Blood samples were taken at several time
      points during a 90 minute circulation period. Changes in coagulation, complement,
      and blood cell alteration factors were measured by ELISA methods, plasma
      bradykinin levels were measured by radioimmunoassay, and expression of genes
      encoding cytokines TNF-alpha, interleukin-1beta, interleukin-6, and interleukin-8
      was determined by semiquantitative real time RT-PCR. Platelet adhesion was
      significantly reduced in both the PMEA and the heparin coated circuits. Release
      of platelet activation marker beta-thromboglobulin was significantly higher in
      the uncoated control group (p < 0.01). After 5 minutes of blood circulation
      bradykinin levels significantly increased in all three groups (p < 0.01);
      however, the group with the PMEA coated oxygenators showed the lowest values.
      Expression of genes encoding proinflammatory cytokines in monocytes was increased
      in all groups, with the lowest being in the PMEA coated group. PMEA coated CPB
      surfaces in an in vitro experimental model showed an improved thrombogenicity,
      reduced bradykinin release, less platelet activation and less proinflammatory
      cytokines gene expression in comparison with a noncoated group. The authors
      assume that PMEA coating may ameliorate some of intra- and postperfusion
      syndromes, particularly hypotension, unspecific inflammation, hyperfibrinolysis,
      and blood loss.

PMID- 15171469
TI  - Experimental testing of a new left ventricular assist device--the microdiagonal
      blood pump.
AB  - All existing ventricular assist devices are associated with a considerable number
      of serious complications. This article reports on the first animal tests with a
      newly developed microdiagonal blood pump (MDP). Six adult female sheep weighing
      80 to 90 kg underwent implantation of the microdiagonal blood pump. The inflow
      and outflow conduits were anastomosed to the left atrium and the descending
      aorta. Pump flow was adjusted to 2-3 L/minute. Hemodynamic and echocardiographic
      data, as well as blood samples, were measured over the entire test period of 7
      days. All internal organs and the pump were explanted for thorough examination at
      the end of the trial. Mean arterial (range 88.5 +/- 13.1-103.7 +/- 10.7 mm Hg)
      and mean pulmonary arterial (18.3 +/- 2.7-21.6 +/- 20.5 mm Hg) pressures, as well
      as the pulmonary capillary wedge pressure (14.2 +/- 3.0 - 16.6 +/- 4.0 mm Hg),
      remained stable during the whole test period. Cardiac output (4.9 +/- 0.7 --> 3.2
      +/- 0.5 L/minute) decreased postoperatively caused by partial unloading of the
      heart. Left ventricular end diastolic (4.1 +/- 0.5 --> 3.6 +/- 0.3 cm) and end
      systolic (3.2 +/- 0.4 --> 2.8 +/- 0.5 cm) diameters, as well as the ejection
      fraction (57 +/- 9 --> 42 +/- 5%), decreased after MDP implantation and did not
      change during the test period. Mean number of platelets (428 +/- 54 --> 286 +/-
      66 x 10(3)/microL) and hemoglobin (9.8 +/- 1.3 --> 6.3 +/- 0.8 g/dL) decreased
      perioperatively because of surgical reasons and increased continuously in the
      postoperative course (platelet count and hemoglobin on day 7:441 +/- 74 x
      10(3)/microL and 7.2 +/- 1.1 g/dL, respectively). Free hemoglobin was not
      enhanced in the postoperative course (mean value during the test period: 18.8
      mmoL/L). Histologic examination of the organs did not demonstrate any infarctions
      of internal organs other than typical operative sequelae such as chronic
      pericarditis and some degree of atelectasis of the left lungs. These results
      demonstrate that the microdiagonal pump may be a promising alternative to the
      currently used ventricular assist devices, if long-term trials support these
      results.

PMID- 15171470
TI  - Observation of cavitation in a mechanical heart valve in a total artificial
      heart.
AB  - Recently, cavitation on the surface of mechanical heart valves has been studied
      as a cause of fractures occurring in implanted mechanical heart valves. The cause
      of cavitation in mechanical heart valves was investigated using the 25 mm
      Medtronic Hall valve and the 23 mm Omnicarbon valve. Closing of these valves in
      the mitral position was simulated in an electrohydraulic totally artificial
      heart. Tests were conducted under physiologic pressures at heart rates from 60 to
      100 beats per minute with cardiac outputs from 4.8 to 7.7 L/min. The disk closing
      motion was measured by a laser displacement sensor. A high-speed video camera was
      used to observe the cavitation bubbles in the mechanical heart valves. The
      maximum closing velocity of the Omnicarbon valve was faster than that of the
      Medtronic Hall valve. In both valves, the closing velocity of the leaflet, used
      as the cavitation threshold, was approximately 1.3-1.5 m/s. In the case of the
      Medtronic Hall valve, cavitation bubbles were generated by the squeeze flow and
      by the effects of the venturi and the water hammer. With the Omnicarbon valve,
      the cavitation bubbles were generated by the squeeze flow and the water hammer.
      The mechanism leading to the development of cavitation bubbles depended on the
      valve closing velocity and the valve stop geometry. Most of the cavitation
      bubbles were observed around the valve stop and were generated by the squeeze
      flow.

PMID- 15171471
TI  - Indirect bronchial shunt flow measurements in AbioCor implantable replacement
      heart recipients.
AB  - Bronchial shunt flows in the recipients of the electrohydraulic AbioCor
      implantable replacement heart have been measured indirectly. A built-in
      compliance chamber accommodates the differential flow output required of the two
      ventricles of the AbioCor. An occluder mechanism regulates the flow differential.
      For a thoracic unit, given a beat rate, an occluder setting, and the pressure
      differentials across the replacement heart ventricles, the atrial pressure
      difference depends only on the level of shunt flow present in the vasculature.
      For a replacement heart recipient, the bronchial shunt is the dominant shunt
      flow. For patients implanted with the AbioCor, the beat rates and the occluder
      settings are known and the pressure differentials across the ventricles are
      estimated. Atrial pressures were measured using catheters. The bronchial shunt
      flow was deduced from in vitro characterization data based on these parameters.
      Available data from five patients in the ongoing clinical trial of AbioCor showed
      0-1.4 L/minute bronchial shunt flows. Maximum variation for any individual
      patient was 1.1 L/minute.

PMID- 15171472
TI  - Design and transient computational fluid dynamics study of a continuous axial
      flow ventricular assist device.
AB  - A ventricular assist device (VAD), which is a miniaturized axial flow pump from
      the point of view of mechanism, has been designed and studied in this report. It
      consists of an inducer, an impeller, and a diffuser. The main design objective of
      this VAD is to produce an axial pump with a streamlined, idealized, and
      nonobstructing blood flow path. The magnetic bearings are adapted so that the
      impeller is completely magnetically levitated. The VAD operates under transient
      conditions because of the spinning movement of the impeller and the pulsatile
      inlet flow rate. The design method, procedure, and iterations are presented. The
      VAD's performance under transient conditions is investigated by means of
      computational fluid dynamics (CFD). Two reference frames, rotational and
      stationary, are implemented in the CFD simulations. The inlet and outlet surfaces
      of the impeller, which are connected to the inducer and diffuser respectively,
      are allowed to rotate and slide during the calculation to simulate the realistic
      spinning motion of the impeller. The flow head curves are determined, and the
      variation of pressure distribution during a cardiac cycle (including systole and
      diastole) is given. The axial oscillation of impeller is also estimated for the
      magnetic bearing design. The transient CFD simulation, which requires more
      computer resources and calculation efforts than the steady simulation, provides a
      range rather than only a point for the VAD's performance. Because of pulsatile
      flow phenomena and virtual spinning movement of the impeller, the transient
      simulation, which is realistically correlated with the in vivo implant scenarios
      of a VAD, is essential to ensure an effective and reliable VAD design.

PMID- 15171473
TI  - Development of a balloon volume sensor for pulsating balloon catheters.
AB  - Helium pulsed balloons are integral components of several cardiovascular devices,
      including intraaortic balloon pumps (IABP) and a novel intravenous respiratory
      support catheter. Effective use of these devices clinically requires full
      inflation and deflation of the balloon, and improper operating conditions that
      lead to balloon under-inflation can potentially reduce respiratory or cardiac
      support provided to the patient. The goal of the present study was to extend
      basic spirographic techniques to develop a system to dynamically measure balloon
      volumes suitable for use in rapidly pulsating balloon catheters. The dynamic
      balloon volume sensor system (DBVSS) developed here used hot wire anemometry to
      measure helium flow in the drive line from console to catheter and integrated the
      flow to determine the volume delivered in each balloon pulsation. An important
      component of the DBVSS was an algorithm to automatically detect and adjust flow
      signals and measured balloon volumes in the presence of gas composition changes
      that arise from helium leaks occurring in these systems. The DBVSS was capable of
      measuring balloon volumes within 5-10% of actual balloon volumes over a broad
      range of operating conditions relevant to IABP and the respiratory support
      catheter. This includes variations in helium concentration from 70-100%,
      pulsation frequencies from 120-480 beats per minute, and simulated clinical
      conditions of reduced balloon filling caused by constricted vessels, increased
      driveline, or catheter resistance.

PMID- 15171474
TI  - Clinical use of the abiomed BVS 5000 as a pulsatile extracorporeal membrane
      oxygenation unit.
AB  - The traditional extracorporeal membrane oxygenation circuit uses a centrifugal
      pump. These pumps require close monitoring and are subject to complications. In
      addition, they do not take advantage of the potential benefits of pulsatile flow.
      These extracorporeal membrane oxygenation circuits use a single pump with an
      inline oxygenator. If cardiac failure persists after respiratory recovery has
      occurred, removal of the oxygenator requires an additional procedure to convert
      the patient to biventricular support. This report describes a circuit in which an
      oxygenator is connected to a pulsatile ventricular assist device. Single and dual
      circuit configurations are illustrated. Recommendations for pulmonary care during
      support are also described.

PMID- 15171475
TI  - Best method for estimating urea volume of distribution: comparison of single pool
      variable volume kinetic modeling measurements with bioimpedance and
      anthropometric methods.
AB  - The urea volume of distribution (Vurea) is a key component of the Kt/V parameter
      calculated during urea kinetic modeling. The Vurea parameter has been
      approximated empirically using total body water (TBW) estimates derived from
      anthropometric formulas or measured by bioelectric impedance analysis (BIA). The
      author compared TBW values derived using various anthropometric formulas (Watson,
      Hume, Randall, Tzamaloukas, Chertow) and BIA to the Vurea parameter calculated
      using three point variable volume single pool urea kinetic modeling. A total of
      127 chronic hemodialysis patients were studied (mean age 66 +/- 13 years; 42%
      female; 37% black; 47% diabetic). Agreement between anthropometric formulas, BIA,
      and Vurea values was assessed by linear regression and Bland Altman analyses. The
      closest correlations were obtained with the BIA (r = 0.972), Chertow (r = 0.917),
      and Tzamaloukas (r = 0.905) methods. When compared with Vurea, 95% confidence
      intervals by Bland Altman analysis were lowest with BIA (4L) and highest with the
      Watson method (8L). These results indicate that BIA best approximates Vurea in
      dialysis patients.

PMID- 15171476
TI  - Measurement of blood volume during hemodialysis is a useful tool to achieve
      safely adequate dry weight by enhanced ultrafiltration.
AB  - Chronic fluid overload and hypertension are highly prevalent in the dialysis
      population. Measurement of blood volume (BV) during hemodialysis (HD) may prove
      useful to achieve dry weight (DW). Twelve (12) chronic hemodynamically stable
      dialysis patients were randomly selected to participate in a pilot study. BV
      changes were measured using an online blood volume monitor (Hemoscan, Gambro AB,
      Stockholm, Sweden). As part of an initial observation phase, the magnitude of BV
      variation (deltaBV) in percentage and total UF volume (UF) in liters were
      recorded for each dialysis session, and the deltaBV/UF ratio was calculated. DW
      was subsequently reduced by 0.5 kg in all patients and the tolerance of the
      procedure was assessed. Attempted DW reduction was successful in seven patients,
      whereas it resulted in hypotension or symptoms in the other five cases. The
      deltaBV/UF ratio was found to be significantly lower in patients in whom
      attempted DW reduction was successful (2.47%/L vs. 3.45%/L, P < 0.05). Using
      receiver operating characteristic (ROC) curve analysis, a deltaBV/UF ratio of
      less than 2.6%/L offered the best overall prediction of successful DW reduction.
      These results suggest that measurement of BV changes during HD and calculation of
      the deltaBV/UF ratio are valuable tools for management of DW in clinically stable
      patients.

PMID- 15171477
TI  - Effect of bleach reprocessing upon the clearance characteristics and surface
      charge of polysulfone hemodialyzers.
AB  - The effects of reprocessing upon hemodialysis have been debated since the
      introduction of this practice. The objective of this study was to develop a
      quantitative understanding of the effects of bleach reprocessing upon Fresenius
      polysulfone dialyzers. Data were obtained for the clearance of urea, vitamin B12,
      and polydisperse dextrans before and after reprocessing, both with and without
      exposure to plasma in a simulated dialysis session. Bleach reprocessing of the
      native dialyzer caused a significant increase in solute clearance because of the
      removal of polyvinylpyrrolidone from the membrane copolymer. This was confirmed
      by zeta potential measurements that showed a substantial increase in the negative
      charge on the membrane surface. Exposure to plasma proteins during hemodialysis
      effectively protected the dialyzer from chemical degradation by the bleach, with
      only small changes in solute clearance after the optimal reprocessing cycle.
      However, inadequate exposure to bleach was unable to restore the original solute
      clearance while over cleaning with bleach caused an increase in clearance.
      Considerable care must be taken in the proper design of reprocessing cycles for
      hemodialysis membranes.

PMID- 15171479
TI  - A neo-esophagus reconstructed by cultured human esophageal epithelial cells,
      smooth muscle cells, fibroblasts, and collagen.
AB  - The scientists involved in this study attempted to develop an artificial
      esophagus constructed of autologous cells grown by cell culture methods on an
      extracellular matrix. An artificial esophagus consisting of human esophageal
      epithelial cells, dermal fibroblasts, and smooth muscle cells isolated from the
      aortic media, was attempted. The purpose of this study was to examine whether
      smooth muscle cells could be used in the transforming matrix. Human fibroblasts
      were embedded in Type I collagen superimposed on the collagen layer of smooth
      muscle cells. Next, human esophageal epithelial cells were cultured on the
      collagen layer of the fibroblasts. The resulting collagen sheets were cultured in
      vitro for 1 week, then transplanted on the latissimus dorsi muscles of athymic
      rats. The sheets were examined histologically at 1 and 2 weeks using hematoxylin
      eosin and immunologic stain methods (antiactin antibody). At the end of 2 weeks
      after transplantation, on microscopic observation of the collagen sheets, it
      appeared that the epithelial layer, the submucosal tissue layer, and the proper
      muscle layer had been reconstructed. Additionally, the authors successfully
      isolated smooth muscle cells from the media of the left gastric artery as a
      surgical specimen by explant cell culture. The ability to transform collagen
      sheets consisting of esophageal epithelial cells, fibroblasts, and smooth muscle
      cells from a surgical specimen into a luminal structure may enable clinical
      application of the artificial esophagus.

PMID- 15171478
TI  - Degradation of low molecular weight uremic solutes by oral delivery of
      encapsulated enzymes.
AB  - An alginate microcapsule was developed that contains three enzymes (urease,
      uricase, and creatininase) capable of effectively degrading urea, uric acid, and
      creatinine, which are elevated to pathologic levels in patients with kidney
      failure. The capsules were evaluated in vitro and in vivo in a rodent model and
      evidenced considerable potential as a possible adjunctive therapy in the
      treatment of ESRD. In vitro, 5 mL of the capsules incorporating a quantity of
      enzymes in the mg range effectively degraded all the uric acid, 97% of the urea,
      and 70% of the creatinine within 24 hours in a 100 mL test solution simulating
      the concentration of these solutes in uremic plasma. Enzyme degradation of urea
      followed Michaelis-Menten kinetics, and the Lineweaver-Burk plots for both
      encapsulated enzymes and unencapsulated control animals were superimposable,
      indicating that mass transfer through the capsules was not rate limiting in the
      degradation process. A chemically induced acute renal failure model in the rat
      was used to evaluate the ability of encapsulated enzymes, along with an oral
      sorbent (ion exchange resin), to degrade uremic toxins in vivo. Encapsulated
      enzyme therapy decreased the severity of azotemia by as much as 70%. Preliminary
      scale up calculations indicated that oral delivery to humans would involve a
      practical and manageable quantity of enzymes. This is the first study using a
      combination of enzymes in a single delivery vehicle to degrade multiple uremic
      toxins.

PMID- 15171481
TI  - Adenovirus mediated endothelial nitric oxide synthase gene transfer prevents
      restenosis of vein grafts.
AB  - The possibility of endothelial nitric oxide synthase (eNOS) gene transfer, which
      prevents restenosis of vein grafts, was explored in 16 goats. The recombinant
      adenoviral vector coding endothelial nitric oxide synthase (AdCMVeNOS) and
      adenoviral vector (AdCMV) were constructed. A total of 6 cm jugular vein was
      removed, cut into two equal lengths for vein grafts, and infected with AdCMVeNOS
      or AdCMV in vitro. One segment (2 cm) of each carotid artery was removed. The
      vein graft that had been infected with AdCMVeNOS was anastomosed to the right
      carotid artery, and the vein graft that had been infected with AdCMV was
      anastomosed to the left. The functional expression of eNOS in vein grafts was
      assessed by the immunohistochemical staining and measurement of NO concentration.
      The inhibition of intimal hyperplasia in vein grafts was evaluated by the assay
      of 3H-TDR incorporation, histologic analysis, measurement of intimal thickness,
      and percent area stenosis. Adenovirus mediated eNOS gene transfer to goat vein
      grafts resulted in functional transgene expression with increased NO release.
      Increased local NO production could inhibit intimal hyperplasia and increase the
      patent rate of vein grafts.

PMID- 15171480
TI  - Baseline hemodynamic and echocardiographic indices in anesthetized calves.
AB  - The experimental calf model is used to assess mechanical circulatory support
      devices and prosthetic heart valves. Baseline indices of cardiac function have
      been established for the normal awake calf but not for the anesthetized calf.
      Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy
      anesthetized calves (mean age, 189.0 +/- 87.0 days; mean body weight, 106.9 +/-
      32.3 kg) by cardiac catheterization and noninvasive echocardiography,
      respectively. Baseline hemodynamic data included heart rate (65 +/- 12 beats per
      minute), mean aortic pressure (113.5 +/- 17.4 mm Hg), left ventricular end
      diastolic pressure (16.3 +/- 38.9 mm Hg), and mean pulmonary artery pressure
      (21.7 +/- 8.3 mm Hg). Baseline two-dimensional echocardiographic data included
      left ventricular systolic dimension (3.5 +/- 0.7 cm), left ventricular diastolic
      dimension (5.6 +/- 0.8 cm), end-systolic intraventricular septal thickness (1.7
      +/- 0.2 cm), end-diastolic intraventricular septal thickness (1.2 +/- 0.2 cm),
      ejection fraction (63 +/- 10%), and fractional shortening (37 +/- 10%). Doppler
      echocardiography revealed a maximum aortic valve velocity of 0.9 +/- 0.5 m/s and
      a cardiac index of 3.7 +/- 1.1 L/minute/m2. The collected baseline data will be
      useful in assessing prosthetic heart valves, cardiac assist pumps, new
      cannulation techniques, and robotics applications in the anesthetized calf model
      and in developing calf models of various cardiovascular diseases.

PMID- 15171482
TI  - Heart blood volume by dilution in patients on hemodialysis.
AB  - Cardiomegaly and accompanying complications contribute to morbidity and mortality
      in patients on hemodialysis. Our objective is to provide a measure of heart blood
      volume from data collected during routine measurement of cardiac output during
      hemodialysis. A heart model based upon the probability of transfer between
      chambers during a cardiac cycle generates both the distribution of transit times
      (dilution curve) and the blood volumes in the chambers of the heart. This heart
      model is combined with a compatible lung model based upon a stochastic
      description of microvascular flow to simulate vasomotion. By exercising the
      heart/lung model systematically over a wide range of probabilities, any chosen
      characteristic of the distribution of transit times can be correlated to total
      heart blood volume for a wide range of heart/lung functional states. For a bolus
      traversing the heart and lung vascular beds, the length of the chord drawn upon
      the dilution curve at half the height of the peak is identified as an efficient,
      robust predictor of the total blood volume in the heart at end ventricular
      diastole. When applied to data previously collected from patients on
      hemodialysis, enlarged hearts were observed in 4 of 60 patients.

PMID- 15171483
TI  - A temporal and spatial analysis of cavitation on mechanical heart valves by
      observing faint light emission.
AB  - Cavitation on mechanical heart valves (MHVs) could cause the mechanical failure
      of the occluder. A simple and reliable in vitro test method to evaluate
      cavitation potential must be developed. The bubble implosion damages the MHV
      material; thus, observing the behavior of the bubble implosion is essential.
      According to sonoluminescence, the collapsing cavity emits faint light.
      Therefore, in this study, the bubble collapse was analyzed both temporally and
      spatially by observing faint light emission. A photon counting system has been
      developed using a photomultiplier tube (H7360-01, Hamamatsu Photonics, Japan).
      The highest time resolution of this system is 5 microsec. A quartz optical fiber
      bundle of 2 mm diameter can be connected to this photomultiplier tube and
      traversed two-dimensionally over the MHV. The closure of the MHV triggers the
      photon counter, and the photons through 500 beats are recorded and integrated. A
      20 mm Bjork-Shiley valve was submerged in a water tank containing 10 L deionized
      water, and the pressure difference of 120 mm Hg was exerted on the valve at a
      rate of 60 bpm with a pulse duplicator. Approximately 700 microsec after the
      valve closure, light emission was detected along the edge of the occluder on the
      inflow side in the major orifice. Then, approximately 1,000 microsec after the
      closure, light along the occluder's edge in the minor orifice was recorded as
      well. Compared with the analysis, using a stroboscope and a high-speed camera,
      faint light was emitted from the collapsing cavities. In conclusion,
      sonoluminescnece was successfully observed around the MHV, and the photon
      counting technique and the traversing mechanism of the optical fiber bundle
      revealed the temporal and spatial distribution of the cavity collapse on the MHV.

PMID- 15171484
TI  - Gestational and lactational exposure to heptachlor does not alter reproductive
      system development in rats.
AB  - Like other organochlorine insecticides, heptachlor is lipophilic and accumulates
      in fatty tissues. Earlier studies suggested that in utero exposure to heptachlor
      decreased fertility in the offspring; neonatal exposure to the closely related
      insecticide chlordane reportedly delayed puberty and disrupted estrous cycling in
      females. We hypothesized that in utero and lactational exposure to heptachlor
      would disrupt the development of the reproductive system in males and females,
      resulting in altered timing of puberty and abnormal gonadal histology and
      reproductive hormone levels. Timed pregnant Sprague-Dawley rats were treated by
      oral gavage with heptachlor in corn oil at doses of 0.5 and 5.0 mg/kg or an
      equivalent volume of corn oil alone daily from gestational day 8 through post
      natal day (PND) 21, the day of weaning (n = 7-8/group). Litters were standardized
      to 4 males and 4 females on the day of birth. Two of the dams in the 5.0 mg/kg/d
      group died. Pups in the highest dose group weighed significantly less than those
      in the other 2 groups on PND 0. All but 1 litter of the 5.0 mg/kg/d group died
      within the first 4 post-natal days. Age at eye opening was delayed with
      increasing heptachlor dose. There was no effect of treatment on pup weight gain
      in the surviving litters, on anogenital distance, age at puberty, nipple
      retention past the infantile period in males, estrous cycling, serum sex steroid
      concentrations, reproductive organ weights, or testicular or ovarian histology.
      These results suggest that heptachlor exposure during gestation and lactation
      does not disrupt development of the reproductive system in rats.

PMID- 15171485
TI  - Trace metal profiles in hair samples from children in urban and rural regions of
      the United Arab Emirates.
AB  - Pollution has increased with industrialization and humans are subjected to
      exposure to heavy metals from different environmental sources. In oil-producing
      countries heavy metals are considered a major threat to the population. Metals
      such as lead, aluminum, manganese, nickel and cadmium may impact various organs
      of the body, and controlling their toxicity is crucial for individuals at risk.
      Previous studies utilized blood levels for monitoring metal toxicity. The current
      study was designed to investigate exposure to lead, aluminum, manganese, nickel
      and cadmium using scalp hair. Hair samples were randomly collected from 42
      children (aged 6-18 y) representing rural and urban areas of the United Arab
      Emirates. The rural regions were defined as at least 50 km away from factories or
      traffic sites. Immediately after cutting, hairs were stored in plastic bags and
      attached to a questionnaire with the relevant background information. Samples
      were dried, weighed and sealed with polyethylene envelopes. Following extraction
      procedures with nitric acid, ICP-MS was utilized for metals determination. The
      analytical instrument showed a high degree of sensitivity and revealed
      significant differences between levels of some metals in hairs from rural and
      urban areas. Children from rural areas had mean hair lead levels (microg/g) of
      0.79 + 0.10 whereas children from urban area had higher hair lead levels (3.47 +
      0.47). Measuring metals concentration in scalp hair could be a useful method for
      studying exposure and assessing environmental pollution. Although the technique
      has the potential of being an effective tool for evaluating extent of pollution
      and identifying potentially toxic elements, it cannot yet replace the standard
      procedures of measuring air, water and soil metal content.

PMID- 15171486
TI  - Efficacy of a commercial mycotoxin binder in alleviating effects of ochratoxin A,
      fumonisin B1, moniliformin and zearalenone in adult mink.
AB  - The addition of nutritionally inert adsorbents to mycotoxin-contaminated animal
      feed has been a popular approach to decreasing toxicity in animals and carryover
      of mycotoxins from contaminated feed to animal by-products. Some studies suggest
      that esterified glucomannan derived from the cell wall of Saccharomyces
      cerevisiae is effective in reducing the bioavailability of at least some of the
      mycotoxins occurring in contaminated feed. Because cereal grains are important
      components of ranch mink diets, mycotoxicoses in mink is a potential problem
      faced by mink ranchers. We conducted a series of studies to determine if
      inclusion of a commercially available esterified glucomannan in ranch mink feed
      was effective in alleviating clinical signs indicative of exposure to ochratoxin
      A, fumonisin B1, moniliformin or zearalenone in adult mink. In 4 separate trials,
      mink were fed diets that contained 2.5, 5 or 10 mg ochratoxin A/kg feed, 200 mg
      fumonisin B1/kg feed, 20 mg moniliformin/kg feed, or 30 mg zearalenone/kg feed
      with or without 2 g esterified glucomannan/kg feed. Male mink fed diets
      containing ochratoxin A had significantly decreased feed intake as well as renal
      lesions characteristic of exposure to that mycotoxin. Inclusion of the esterified
      glucomannan did not ameliorate these effects. Male mink exposed to fumonisin B1
      had increased urinary sphinganine concentration, which was not significantly
      reduced by the mycotoxin adsorbent. Male mink that consumed monilformin
      contaminated diets had characteristic ultrastructural changes in the heart that
      were not reduced in severity by the esterified glucomannan. Female mink exposed
      to zearalenone had increased uterine weight, which was not reversed by inclusion
      of commercial mycotoxin binder in the contaminated feed. The results of this
      study suggest that a commercial esterified glucomannan was generally ineffective
      in alleviating effects indicative of exposure to ochratoxin A, fumonisin B1,
      monilformin and zearalenone in mink.

PMID- 15171487
TI  - Acute oxcarbazepine and atomoxetine overdose with quetiapine.
AB  - We present a case of acute oxcarbazepine and atomoxetine overdose combined with
      excess quetiapine in a 19-y-old male. The patient ingested approximately 36 g
      oxcarbazepine (514 mg/kg), 1.2 g atomoxetine (17 mg/kg), and 9 mg Quetiapine (128
      mg/kg). Central nervous system (CNS) depression with initial unresponsiveness
      developed within 1 h of ingestion, necessitating intubation for airway
      protection. Despite aggressive therapy with whole bowel irrigation and charcoal
      administration, the patient's somnolence persisted for 4 d, punctuated by
      occasional violent outbursts. Prolonged QTc was noted initially, but normalized
      within 4 d. This case suggests that acute overdose of oxcarbazepine and
      atomoxetine combined with quetiapine is associated with rapid and prolonged CNS
      depression.

PMID- 15171489
TI  - Mushroom poisonings in children in Central Anatolia.
AB  - The aim of this study was the analysis of mushroom poisonings (MP) in children in
      Central Anatolia. Cases younger than 18 y-of-age, who presented and were
      diagnosed as MP between January 1991 and December 2002 were evaluated for gender,
      age, presenting month, city of residence, first noticed symptoms, vital signs,
      laboratory studies, hospitalization period and outcome. Sixty-four cases were
      enrolled; 36 were female (56.3%). The mean age was 8.6 y. May and June were the
      most common presenting months, with 46 cases (71.8%); 61 cases (95.3%) were
      poisoned by wild mushrooms (WM). The most common first noticed symptoms were from
      the gastroinal system (GIS) (70.6%); 67.2% of cases presented to second level
      health centers when the first symptoms started; 92.2% were admitted to the
      hospital. Mean hospitalization period was 2.8 d. Five cases (7.8%) had a fatal
      outcome. All the fatal cases were from WM poisoning and from the same city. Their
      first noticed symptoms were GIS symptoms. All fatal cases had delayed
      presentations. Cultivated MP did not result in bad outcomes in the pediatric age
      group. WM were the main source of MP in children in our region in Turkey.
      Education of the public about consuming mushrooms, and health personnel working
      in health centers for early treatment and transfer to the appropriate facility
      are important to decrease mortality.

PMID- 15171488
TI  - Lead exposition by gunshot ingestion in red-legged partridge (Alectoris rufa).
AB  - Absorption of low concentrations of lead may result in a wide range of sublethal
      effects in birds. Although waterfowl appear the most severely affected group for
      this heavy metal, leadpoisoning-mortality has been observed in a wide variety of
      bird species, ie raptors and upland game birds. In this present work, hepatic
      lead levels in different red-legged partridges are presented to indicate
      threshold values which could help in future toxicological studies when
      considering the lack of information about lead poisoning of such birds in the
      wild.

PMID- 15171490
TI  - Massive intracranial hemorrhage associated with the ingestion of dimethyl
      sulfoxide.
AB  - Dimethyl sulfoxide (DMSO) has been widely used in the treatment of arthritis and
      certain inflammatory diseases, and is also considered an alternative remedy for
      cancer even if not supported by concrete evidence. This report illustrates the
      first case of a fatal complication following the illicit use of this agent. A 55
      y-old man who reportedly ingested 500 mg acetaminophen and approximately 1 ml
      DMSO solution was brought to the emergency department after experiencing 2 tonic
      clonic seizures. He had been diagnosed with lung mesotelioma with brain
      metastases which caused no neurologic deficit. The ingested DMSO was the first
      dose within the last 3 mo. Examination revealed right-sided hemiplegia.
      Unenhanced computed tomography of the head showed 3 hemorrhagic areas with blood
      cerebrospinal fluid at the left parietal, occipital and frontal regions
      accompanied by a midline shift. Despite initial resuscitation, 2 units of fresh
      frozen plasma and antiedema treatment, the patient experienced cardiac arrest
      that did not respond to resuscitative measures. DMSO can cause massive
      intrametastatic hemorrhage, and neurologic deterioration can be profound in
      patients with metastatic brain lesions.

PMID- 15171492
TI  - A review of acute poisoning from Atractylis gummifera L.
AB  - Atractylis gummifera is a poisonous plant widely found in North Africa. The
      thistle grows commonly in dry areas, and the juice of the rhizome is poisonous.
      It provokes frequent poisoning, especially of children. Toxic glucosides have
      been isolated and their identified as atractyloside and carboxyatractyloside.
      Tissues of high metabolic activity are the main target organs. Atractylis
      gummifera glucosides cause a severe hepatitis with fatal liver failure common.
      The plant's poisonous compounds interact with detoxication and/or transformation
      systems in the liver even at doses not likely to induce cytolysis by blocking ADP
      ATP conversion through inhibition of P450 cytochrome. Clinical manifestations are
      related to an induced hypoglycemia and neurovegetative disorders or subsequent
      renal failure. Liver transplantation or immunotherapy may improve the often fatal
      prognosis.

PMID- 15171491
TI  - Acute metaldehyde poisoning in Taiwan.
AB  - Metaldehyde, a cyclic tetramer of acetaldehyde, is a widely used molluscicide.
      Although cases with acute metaldehyde poisoning have been reported, the
      occurrence of severe poisoning is uncommon. To provide more information on human
      metaldehyde poisoning, we reviewed 15 cases of metaldehyde exposure reported to
      the Taiwan National Poison Control Center at the Taipei Veterans General Hospital
      between 1991 and 2002. While 7 patients were asymptomatic, the other 8 patients,
      including 4 who coingested alcohol or other poisons, exhibited toxic
      manifestations of abdominal pain, dizziness, nausea, irritation of oral mucosa,
      and seizures after oral exposure. One patient died after ingesting 12 g (or 258.6
      mg/kg) of metaldehyde. Although the toxicity from metaldehyde is largely mild,
      the clinical course of metaldehyde poisoning may be rapidly deteriorating and
      fatal on rare occasions. Physicians should therefore be cautious in managing
      patients with metaldehyde poisoning, and vigorous supportive measures should be
      promptly instituted in patients who manifest severe toxicity.

PMID- 15171493
TI  - Equine goiter associated with excess dietary iodine.
AB  - Naturally occurring goiter cases are described in 2 newborn Arabian foals whose
      mares were supplemented with excess iodine during the final 24 w of the
      pregnancy. Six nursing foals and 2 mares were also affected clinically with
      thyroid hypertrophy. At least 12 times the maximum tolerable level of iodine
      supplementation was given, as the daily iodine intake for each mare was 299 mg.
      The prevalence of goiter cases was 2 and 9% in the mares and foals, respectively.

PMID- 15171494
TI  - Was it necessary to add Bitrex (denatonium benzoate) to automotive products?
AB  - Oregon was the first state to mandate the addition of a bitter aversive agent to
      consumer automotive products containing > or = 10% ethylene glycol (EG) or > or =
      4% methanol (MeOH). The 1995 Toxic Household Products statute required the
      addition of denatonium benzoate at a concentration of 30-50 ppm with the intent
      to reduce the frequency of serious pediatric exposures to these products.
      Retrospective review included Oregon Poison Center (OPC) records of all reported
      pediatric (< 6 y) exposures to automotive antifreeze (EG) and windshield washer
      fluid (MeOH) from 1987 through 2003, OPC charts of children treated with ethanol,
      fomepizole, or hemodialysis for EG or MeOH poisoning from 1987 through 2002, and
      coroner reports of poisoning deaths for 1994-1997 to identify EG or MeOH deaths
      not reported to the OPC. OPC recorded 332 EG and 117 MeOH exposures among
      preschool children from 1987-2003 with no change in annual frequency after 1995.
      No child died or suffered "major" effects before or after 1995. Ten children
      received ethanol infusions until laboratory results were available; 9 had no
      detectable concentration of the suspected agent, and 1 had a sub-toxic
      concentration. Two children received fomepizole but had no detectable EG. No
      child underwent hemodialysis. Coroner reports detected no missed pediatric deaths
      from toxic alcohols in 1994-1997. The mandatory addition of denatonium benzoate
      was unnecessary as unintentional ethylene glycol or methanol exposures in pre
      school age children did not cause measurable toxicity.

PMID- 15171495
TI  - Beware of canine Gorilla Glue ingestions.
AB  - Household adhesive ingestions are considered relatively non-toxic. Gorilla Glue
      is a household glue containing a urethane polymer and a polymeric isocyanate
      liquid compound available in container sizes of 2 to 36 oz, and when applied will
      expand to 3-4 times its original volume. We report the ingestion of Gorilla Glue
      by 2 dogs that caused obstructive masses requiring surgical intervention. Dogs
      with a history of Gorilla Glue ingestion should be monitored closely by their
      owners and a veterinary referral made if signs of gastrointestinal distress
      develop.

PMID- 15171496
TI  - Is mass-mailing an effective form of passive poison center awareness enhancement?
AB  - This project determined whether the massive distribution of poison center
      telephone number (Poison Help 800-222-1222) awareness stickers via a direct mail
      campaign, as a passive education technique, enhanced poison center awareness and
      was cost-effective. A regional ambulance service conducts an annual membership
      renewal/solicitation drive via mail to all residents within its service area. A
      sheet of Poison Help stickers was inserted in each ambulance service recruitment
      envelope and mass-mailed in 3 separate mailings over 4 w to 51% of households in
      a single county (population 368,983) at a direct expense of 4,477 dollars. Call
      volumes from zip codes that received the mailing were compared to an identical
      benchmark time period from the previous year. Analysis of call volume data over
      the study period revealed that call volume decreased by 1.3% during the study
      period. A mass-mail campaign to enhance poison center awareness failed to
      increase poison center call volume from the targeted county and, cannot be
      construed as cost-effective.

PMID- 15171497
TI  - Good things come three at a time--don't they?

PMID- 15171498
TI  - Acute iron intoxication.

PMID- 15171499
TI  - Life threatening tongue angioedema.

PMID- 15171500
TI  - Pain and stress in the human fetus.
AB  - It is not known if the fetus can actually feel pain, but noxious stimulation
      during fetal life does cause detectable stress responses. These responses cause
      both short and long-term changes in the central nervous system, which can affect
      subsequent pain behaviour. Reducing the stress response is known to be beneficial
      in children and adults and recent evidence suggests this is also true for the
      fetus. However, the optimal amount of suppression required and the best method of
      achieving this (opioid or regional anaesthesia techniques) remain unknown.
      Prevention and treatment of pain is a basic human right, regardless of age, and
      if the technique of fetal surgery is to progress then a greater understanding of
      nociception and the stress response is required.

PMID- 15171501
TI  - Ethical issues in fetal surgery research.
AB  - Research in fetal surgery is currently ethically controversial, especially
      because it poses risks to both the fetus and the pregnant woman. We provide an
      ethical framework for fetal surgery research based on the concept of the fetus as
      a patient. This framework results in criteria for preliminary investigation of
      new fetal surgery techniques, for the initiation and termination of clinical
      trials, the informed consent process, inclusion or exclusion of women based on
      abortion preferences and the obligations of physicians to refer patients to fetal
      research protocols. We demonstrate the applicability of this framework to fetal
      surgery research for spina bifida, a common fetal anomaly.

PMID- 15171502
TI  - Fetal endoscopic surgery: indications and anaesthetic management.
AB  - Fetal intervention for certain life-threatening conditions has progressed from
      being primarily experimental in nature to the standard of care in certain
      circumstances. While surgical techniques have advanced over the past few years,
      the anaesthetic goals for these interventions have remained the same; namely,
      minimizing maternal and fetal risk as well as maximizing the chances of a
      successful fetal intervention and optimize the conditions necessary to carry the
      fetus to term gestation. Fetal endoscopic techniques allow access to the fetus
      without the need for a hysterotomy incision, thus improving the chances of
      controlled post-operative tocolysis and term gestation after fetal intervention.
      This procedure, however, is not without associated risks to both fetus and
      mother. This chapter will address the fetal diseases that may benefit from
      fetoscopic intervention, the rationale behind why maternal and fetal anaesthesia
      is required, the various anaesthetics used for these cases and specific
      considerations of both maternal and fetal physiology that aid in the
      determination of the best anaesthetic technique for individual cases. Methods of
      intra-operative fetal monitoring and fetal resuscitation will also be discussed.

PMID- 15171504
TI  - Anaesthetic considerations for the management of very low and extremely low birth
      weight infants.
AB  - The opportunities for very low birth weight infants (birth weight < 1500 g) and
      extremely low birth weight infants (birth weight < 1000 g) to undergo surgery are
      increasing. These infants are prone to prematurity-related morbidities including
      respiratory distress syndrome, intraventricular haemorrhage, periventricular
      leukomalacia, retinopathy of prematurity, patent ductus arteriosus and
      necrotising enterocolitis. Evidence is accumulating that preterm infants are also
      sensitive to pain and stress. The pharmacokinetics of drugs in preterm infants is
      not fully understood but smaller doses of anaesthetic drugs are usually required
      in preterm infants compared to term infants and older children and their effects
      last longer due to low clearance rates and longer elimination half-lives. Key
      anaesthetic considerations are (i) inspired oxygen concentration that should be
      adjusted to avoid hyperoxia, (ii) haemodynamic parameters that should be kept
      stable and (iii) prevention of hypothermia by using adequate measures to keep the
      infants warm. These precautions must be continuously taken during the operation
      and the transport to and from the operating theatre.

PMID- 15171503
TI  - Ex utero intrapartum surgery (EXIT): indications and anaesthetic management.
AB  - The ex utero intrapartum treatment (EXIT) procedure is a technique for safely
      managing airway obstruction at birth, in which placental support is maintained
      until the airway is evaluated and secured. In addition to the usual
      considerations of anaesthesia in obstetrics there are special considerations
      relating to the EXIT procedure: maintaining fetoplacental circulation by profound
      uterine relaxation and achieving fetal anaesthesia for airway manipulations. This
      chapter focuses on the key issues involved in managing this procedure: the
      indications, preoperative concerns, organization of a multidisciplinary team,
      problems of maternal and fetal anaesthesia, maintenance of the uterine relaxation
      and control of fetal airway.

PMID- 15171505
TI  - Pain, opioid tolerance and sensitisation to nociception in the neonate.
AB  - Pain is commonplace in newborn infants. Opioid analgesics have become
      increasingly used to reduce different types of pain in neonates, including pain
      from surgery, medical procedures and chronic conditions. Adverse effects of
      opioids include respiratory depression, hypotension and tolerance. These adverse
      effects can be minimised by utilising specific administration techniques and
      constant monitoring. Recent studies have demonstrated that untreated pain can
      have long-term effects on infant pain behaviours months beyond the events, thus,
      opioid analgesics may have a beneficial role that extends beyond the immediate
      painful event(s).

PMID- 15171506
TI  - Anaesthesia for neonatal thoracic surgery.
AB  - Anaesthetic care during thoracic surgical procedures in neonates combines
      components of the knowledge bases of neonatal anaesthesia with those of thoracic
      anaesthesia. This chapter reviews the principles of anaesthesia during thoracic
      surgery in neonates including the pre-operative evaluation, anaesthetic induction
      techniques, maintenance anaesthesia and options for post-operative analgesia. In
      addition, given the need to provide optimal surgical visualisation during these
      procedures, one-lung ventilation (OLV) may be required. Techniques to provide OLV
      in the neonate and the principles of anaesthetic care during OLV are reviewed.
      Finally, specific scenarios of neonatal thoracic surgery are reviewed including
      anaesthetic care during: (1) laryngoscopy and rigid bronchoscopy, (2)
      thoracoscopy, (3) repair of tracheo-oesophageal fistula, (4) resection of
      congenital cystic adenomatoid malformation, and (5) treatment of congenital lobar
      emphysema.

PMID- 15171507
TI  - Major abdominal surgery of the neonate: anaesthetic considerations.
AB  - The anaesthetic handling of neonates scheduled for major abdominal surgical
      procedures is one of the most demanding tasks that can confront an
      anaesthesiologist. This chapter will review the specific physiological
      characteristics of the newborn with relevance to anaesthesia and will also
      provide robust guidelines for the anaesthetic handling of the most frequent
      diagnoses that need major abdominal surgery during the neonatal period.

PMID- 15171508
TI  - Anaesthetic considerations for laparoscopic surgery in neonates and infants: a
      practical review.
AB  - Minimally invasive surgery is being applied to an increasing number of neonates
      and infants undergoing abdominal surgeries. Knowledge of specific implications,
      patient's health status and pathophysiological changes induced by the surgery
      allow the anaesthesiologist to provide safe anaesthesia to these high-risk
      patients. This chapter describes the specific pathophysiological effects, peri
      operative management, major complications and contraindications related to
      endoscopic procedures.

PMID- 15171509
TI  - Regional anaesthetic techniques for neonatal surgery: indications and selection
      of techniques.
AB  - The goal of neonatal care is to optimise the outcome of term and preterm infants
      with minimal suffering. Neonates are rare patients for the anaesthetist,
      therefore personal and even global experiences are limited. This chapter focuses
      on strategies for dealing with common clinical situations, e.g. heel lancing,
      obtaining vascular access, circumcision, hernia repair and pyloric stenosis, as
      well as major neonatal surgery. With the exception of heel lancing, regional
      techniques are useful in all cases. However, a careful risk-benefit analysis is
      mandatory, especially when considering more invasive techniques such as epidural
      catheters.

PMID- 15171510
TI  - [Diabetes update: preventing type 2 diabetes. Individualized stepwise therapy
      (oral antidiabetic agents). Multifactorial intervention].
AB  - Preclinical disorders of glucose metabolism should be systematically included in
      the high-risk group for diabetes mellitus and affected individuals provided with
      preventive measures. Their underlying insulin resistance is determined with the
      help of a checklist and a method called homeostasis model assessment (HOMA).
      Patients with impaired fasting glucose (IFG) must change their lifestyles. If
      this does not lead to a response or the patient is unable to modify behavior,
      medication is required. In the case of manifest type 2 diabetes mellitus, a
      graded schedule is used for differential management, which should be based on
      nutritional and exercise therapy. Oral medication with metformin is probably the
      drug of choice in both obese and non-obese patients. It is crucial not to delay
      raising the level of treatment until HbA1c has fallen to within an unsatisfactory
      range (wait-and-see strategy). Rather, the level should be intensified when
      persistent exacerbation starts to become apparent (proactive therapy). In
      diabetes mellitus, the same guidelines for secondary prevention apply to the
      associated cardiovascular risk factors as with coronary heart disease. An
      intensified and, especially, early treatment is to be preferred over a
      conservative, wait-and-see approach, in this case as well.

PMID- 15171511
TI  - [Exacerbations of COPD--new aspects in pathogenesis and therapy].
AB  - Exacerbations of COPD are a common cause of morbidity and mortality in this
      chronic lung disease. Many exacerbations are caused by bacterial or viral
      infections, but the cause of about 30% of exacerbations cannot be identified.
      Clinical symptoms (increased dyspnea, cough, and sputum) are due to increased
      inflammation of the central and peripheral airways, resulting in increased mucus
      production and bronchoconstriction. Home management consists of an intensive
      bronchodilator therapy (beta-agonists and anticholinergics), oral
      glucocorticosteroids and possibly antibiotics, depending on the clinical
      situation. Hospitalisation has to be considered if initial medical management
      fails, if there are significant co-morbidities or complications, or if the
      underlying COPD is severe. Several possibilities to prevent recurrence of COPD
      exacerbations are discussed.

PMID- 15171513
TI  - [Severe vertigo after a scuba-dive to 29 meters].
AB  - A 27-year-old flight instructor experienced 5 to 10 minutes after a scuba-dive to
      29 m, which lasted totally 50 minutes, dizziness, nausea and severe vertigo. The
      symptoms lasted about an hour. The patient vomited several times and noted sudden
      onset headache and vertigo lasting the following three days. Hyperbaric oxygen
      therapy was started 30 hours after the event because decompression sickness was
      suspected. Transthoracic echocardiographic evaluation showed a patent foramen
      ovale. Diving accidents may be caused by decompression sickness, the formation of
      a free intravascular gas phase (bubbles) may result in transatrial shunting in
      the presence of a patent foramen ovale and may lead to neurological signs and
      symptoms. In this context the diver was advised to undergo closure of the atrial
      septal defect. Five months after the incident the patient underwent successful
      transcatheter occlusion of the PFO.

PMID- 15171512
TI  - [Crystal-induced arthritides].
AB  - Crystal-induced arthritides are problems the general practitioner is often
      confronted with. Most patients present themselves more with acute than with
      chronic inflammatory joint diseases. However, secondary osteoarthritis is a
      frequent cause of disability in chronic disease. Problems of differential
      diagnosis arise because of constitutive symptoms such as fever and malaise in
      acute states of the disease and require exclusion of bacterial infection and of
      other systemic rheumatic diseases. This minireview will cover the clinical
      presentation and differential diagnosis of as well as the therapeutic approaches
      to the most frequent forms of crystal-induced arthritides.

PMID- 15171514
TI  - [Complementary medicine. Help from nature in infertility?].

PMID- 15171515
TI  - The pattern and management outcomes of splenic injuries in the Assir region of
      Saudi Arabia.
AB  - BACKGROUND: In the last decade or so, the management of splenic injuries has
      undergone a lot of debate and changes including refinement of the indications for
      non-operative management (NOM). The aims of this retrospective study are: to
      characterize the pattern of splenic injuries in the Abha region of Saudi Arabia;
      to analyze the mechanisms of injury; and to review the treatment modalities
      employed and their outcome. DESIGN: This is a retrospective chart review.
      SETTING: Assir Central Hospital, Abha (A level II regional trauma centre).
      PATIENTS: All 61 patients above the age of twelve years admitted into the
      hospital with splenic injuries over the nine year period from May 1994 to May
      2003 formed the basis of the study. OUTCOME MEASURES: These included
      complications during management and mortality. Detailed analyses of the outcome
      measures were carried out using the student t test, chi-square test, and means.
      RESULTS: The mean age of the patients was 29.75 +/- 15.13 years. M:F ratio =
      29.5:1. The splenic injury was caused predominantly by motor vehicular accidents
      (MVA) (52 patients--87.2%). High speed, non-use of seat belts, major vehicular
      deformity, car rollover and lack of air bags in the vehicles were the major
      characteristics of the MVA. The main clinical presenting features in the patients
      were related to blood loss, associated head and chest injuries. The mean duration
      of hospital stay was 18.8 +/- 21.31 days (Range = 1-123 days). There was no
      significant correlation between the haemoglobin on admission and the haemoglobin
      six hours after admission (Pearson correlation coefficient = 0.303, p = 0.057).
      The mean volume of blood transfused in the first 24 hours of admission was
      1,788.75 ml +/- 842.65 (range = 250-4,000 cc). Splenectomy was performed in 58
      patients (95.1%) while the remaining 3 (4.9%) were managed conservatively. The
      complications that had significant effect on clinical outcome, especially
      mortality, included bronchopneumonia (p=0.001), brain death (p=0.000), renal
      failure (p=0.005), cardio-respiratory arrest (p=0.000), and hypovolaemic shock
      (p=0.005). CONCLUSIONS: Splenic injuries are caused predominantly by MVA and the
      presentation is determined by the injuries in other organs or systems.
      Complications that develop during treatment do impact on mortality.

PMID- 15171516
TI  - Obstetric urogenital fistula: the Ilorin experience, Nigeria.
AB  - A study of thirty-four cases of obstetric urogenital fistula managed over a ten
      year period (1st January, 1989 to 31st December, 1998) at the University of
      Ilorin Teaching Hospital is reported. The incidence of obstetric urogenital
      fistula is 1.1 per 1000 births. The condition is associated with illiteracy and
      poorly supervised delivery. The peak incidence is in 15-19 years age group and
      primipara accounting for 26.5% and 50% respectively. Prolonged obstructed labour
      was the most common aetiological factor in 28 (82.4%) of cases. Juxta-cervical
      region was the most common site of obstetric urogenital fistula. Eight (23.5%)
      patients were separated/divorced from their husbands. Obstetric urogenital
      fistula can be prevented by improving socio-economic condition of the populace,
      educating the populace to utilize health facilities and advice against teenage
      pregnancy. Labour should be supervised by trained health personnel and difficult
      labour referred early to appropriate health care facility.

PMID- 15171517
TI  - Pharmacokinetics and saliva secretion of paracetamol in healthy male Nigerians.
AB  - A preliminary pharmacokinetic study of paracetamol was carried out in Nigerians
      for whom it is normal to consume paracetamol or its combination during almost any
      type of symptoms. After a single oral dose of 1000 mg of the drug to eight adult
      male volunteers, paracetamol was measured in plasma and saliva using high
      performance liquid chromatography. The plasma profile showed a biexponential
      decline after peak absorption. Some of the pharmacokinetic parameters compared
      with previous results from Caucasians and Asians although some differences were
      observed. The absorption of paracetamol was rapid with mean tmax of 0.875 +/-
      0.44 h (range, 0.5-1.5 h) and was 20 times faster than elimination rate. The Cmax
      varied between 11.46 and 26.44 microg mL(-1) with three of the subjects having
      Cmax greater than the 20 microg mL(-1) limit for therapeutic level. The
      elimination half-life was slightly longer than previous reports, with four
      subjects having t(1/2) above 3 h. The t(1/2) was found to correlate significantly
      (p < 0.01) with the mean residence time (MRT), an indication that MRT can be used
      where t(1/2) cannot be evaluated. The oral clearance was slightly lower (about
      25%) than earlier reports in some Caucasians and Asians. The absorption
      parameters from saliva (Cmax, tmax, AUC and saliva levels) correlated well (r =
      0.88 to 0.999) with those from plasma. The plasma levels were higher than saliva
      in all the subjects studied with variable S/P ratio of 0.64 +/- 0.1 in contrast
      to ealier reports of S/P ratios above unity. In conclusion, the pharmacokinetics
      of paracetamol in Nigerians shows possibility of higher plasma levels and slower
      clearance from the body.

PMID- 15171518
TI  - Cardiovascular autonomic neuropathy in non-diabetic Nigerian patients with
      chronic renal failure.
AB  - AIMS: To determine the frequency of cardiovascular autonomic neuropathy (CAN),
      its pattern and clinical predictors in Nigerians with non-diabetic chronic renal
      failure (CRF). METHODS: A total of 120 subjects comprising 60 pre-dialysis CRF
      patients and an equal number of age- and sex-matched healthy controls were
      studied. Five standard cardiovascular reflex (CVR) tests namely: heart rate
      response to deep breathing, Valsalva manoevre and posture, as well as blood
      pressure response to hand grip and posture were used to evaluate the cardiac
      autonomic functions. A pre-tested questionnaire was administered, with
      neurological examination and serum biochemical investigations also included in
      the evaluation. RESULTS: The frequency of CAN in non-diabetic CRF was 65%.
      Dysfunction of both the parasympathetic and sympathetic divisions of the ANS
      occurred in CRF patients. Significant impairment in all the heart rate reflex
      tests (39%) and blood pressure response to the handgrip tests (28%) occurred in
      patients with CAN. Symptoms of autonomic neuropathy with clinical correlation
      with CAN included: constipation (60%), hyposialism (51%) and hypohidrosis (33%),
      whilst those of peripheral neuropathy were: loss of sensation (50%) and numbness
      (40%). Of the biochemical parameters, serum creatinine and urea had significant
      correlation with autonomic neuropathy. CONCLUSION: Autonomic neuropathy is common
      in Nigerian patients with non-diabetic CRF, especially in those with symptoms of
      constipation, hypohidrosis, numbness and prickly sensations.

PMID- 15171520
TI  - Ultrasonic measurement of biparietal diameter and femur in foetal age
      determination.
AB  - Our objective was to verify ultrasonic measurement of biparietal diameter and
      femur in foetal age determination in the second and third trimester of pregnancy.
      The prospective cross sectional study was carried out at the ultrasound
      department of Aberdeen Maternity Hospital Scotland. The study population
      consisted of 716 pregnant Scottish (Caucasian) women who were certain of their
      gestational ages and had their gestational ages confirmed in the first trimester
      by ultrasound. The findings revealed: (1) Linearity through out pregnancy using
      the femur length measurements while that of the biparietal diameter demonstrated
      poor correlation after 32 weeks of gestation. (2) The standard deviation and the
      correlation coefficient of the femur length measurements were 0.0042 and 0.9920
      respectively while the corresponding values for biparietal diameter were 0.0045
      and 0.9850 respectively. (3) The standard error for femur length estimate was
      0.2251 as against 0.3009 for biparietal diameter estimate. The results suggest
      that femur length measurement is a more reliable index of late third trimester
      gestational age prediction than biparietal diameter.

PMID- 15171519
TI  - Diagnosis of Helicobacter pylori infection correlation between clo-test (urease
      enzyme) and gastric mucosal histology.
AB  - BACKGROUND: There are few histopathologists in West African region. Histology
      results on gastric mucosal biopsies for Helicobacter pylori (HP) usually take
      between one to two weeks to be out. On the other hand, clo-test results for
      Helicobacter pylori can be read between 5 minutes to 24 hours. Is one justified
      to commence therapy based on the clo-test ahead of the histology result? Where
      there is no histopathology services as in many centers in West Africa can one
      rely on clo-test alone? AIM: To evaluate the correlation between clo-test
      (urease) and histological findings of gastric mucosal biopsies. DESIGN:
      Prospective study. SETTING: Endoscopic unit of Obafemi Awolowo University
      Teaching Hospital Complex, Ile-Ife, Nigeria. PATIENTS: Twenty duodenal ulcer (DU)
      patients seen consecutively in the endoscopy unit. INTERVENTION: Upper
      gastrointestinal tract endoscopy, antral biopsies for the clo-test and
      histopathology. RESULT: There was 100% correlation between the clo-test and
      histological findings among all the 20 patients. CONCLUSION: Clo-test (urease) is
      reliable enough to be used to commence therapy aimed at ulcer healing and HP
      eradication.

PMID- 15171521
TI  - Sudden cardiac death in Nigerians--the Ile-Ife experience.
AB  - OBJECTIVE: To determine the clinico-pathologic features, circumstances of death
      and related epidemiological variables in cases of sudden cardiac death among
      Nigerians. METHODS: A review of all cases of medico-legal autopsies performed at
      the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, on
      cases of sudden unexpected deaths over a ten-year period (1987-1997). RESULTS:
      The records of 2,529 medico-legal autopsies were reviewed, of which 79 were found
      to be cases of sudden cardiac deaths (SCD). The SCD cases consisted of 59 males
      (74.7%) and 20 females (25.3%), with age ranging from 27 to 80 years. The mean
      age (and standard deviation) was 53.7 (+11.2) and 52.2 (+10.9) for males and
      females respectively. A total of 68 cases (86.1%) were brought dead into the
      hospital and 38 (55.1%) of these were apparently healthy prior to death. The
      nature of activities associated with SCD, where such was documented, was passive
      in 90% of cases. Hypertensive heart disease was the cause of death in 66 cases
      (83.5%), of which only 20 (30.3%) were previously diagnosed. Ischaemic heart
      disease and cardiomyopathies ranked next as the most common cause of death with 5
      cases (6.3%) each. CONCLUSION: Hypertensive heart disease is the most common
      cause of sudden cardiac death in Nigerians, and many of hypertensive cases were
      previously undiagnosed. Cases of coronary heart disease and myocardial infarction
      played significant roles as causes of sudden cardiac death, indicating that their
      incidence may not be as rare among Nigerians as previously thought.

PMID- 15171522
TI  - Tracheostomy in surgical practice: experience in a Nigerian tertiary hospital.
AB  - BACKGROUND: Tracheostomy continues to be a standard surgical procedure for airway
      management. OBJECTIVE: This study was conducted to evaluate the indications, and
      complications associated with the utilization of open surgical tracheostomy in
      our center. DESIGN AND SETTING: It is a retrospective study of all patients that
      had open surgical tracheostomy at the Obafemi Awolowo University Teaching
      Hospital, Ile-Ife. Nigeria during a 15-year period between January 1986 and
      December 2000. PATIENTS AND METHODS: The medical records of the forty-four
      patients that had open surgical tracheostomy in the operating theatre within the
      study period were evaluated. RESULTS: There were 12 females and 32 males. The
      mean age was 33.6 +/- 24.8 years. The indications for tracheostomy were trauma (n
      =15), infections (n = 13), laryngeal (benign and malignant) tumors (n = 9), other
      head and neck malignancies (n = 4), neurological cases with respiratory failure
      (n = 2), and tracheomalacia (n = 1). All the tracheostomies were performed as an
      emergency as all the patients presented in respiratory obstruction. Transverse
      incision was employed in n = 35 cases, while the longitudinal incision was
      employed in n = 3 and the type of incision was not specified in the remaining six
      cases. Laryngeal stenosis was found in 6.9% of cases and the mortality was 25%.
      CONCLUSION: Upper airway obstruction was the major indication for tracheostomy in
      our center; and the high mortality may be due to the primary medical problems
      rather than the complications of tracheostomy alone.

PMID- 15171523
TI  - Long-term outcome of posterior urethral valves ablation using the Mohan's
      urethral valvotome.
AB  - CONTEXT: Posterior urethral valves are the most common cause of mechanical
      infravesical obstruction in children. The disorder has a broad spectrum of
      severity and the patients could develop complications on the long term, even
      after valves ablation. OBJECTIVE: To report the result of the follow-up study of
      26 children who had posterior urethral valves ablated with the Mohan's urethral
      valvotome at the University college hospital, Ibadan over a period of five years.
      STUDY DESIGN SETTING AND SUBJECTS: Children who had posterior urethral valves
      ablated with the Mohan's urethral valvotome at the UCH, Ibadan between January
      1996 and December 2000 were followed up in the out patient clinic on a regular
      basis. RESULTS: A total of 26 patients with posterior urethral valves had the
      valves ablated with the Mohan's urethral valvotome during the period of the
      study. The period of follow-up varied between 18 months and five years. Problems
      noticed on follow-up include recurrent urinary tract infections in 35% of the
      cases, acute and chronic renal failure in 5% and 15% respectively, rickets,
      anaemia, malnutrition and urethral stricture. CONCLUSION: Children who had
      posterior urethral valves ablated should be followed up much beyond the immediate
      post valve ablation period as complications could arise on the long term.

PMID- 15171524
TI  - Prediction of difficult laryngoscopy in a population of Nigerian obstetric
      patients.
AB  - Difficulty in the maintenance of the airway during obstetric anaesthesia is a
      major contributory factor in anaesthetic related morbidity and mortality. There
      is an eightfold increase in the incidence of failed intubation in obstetrics.
      This is attributable to the physiological changes in pregnancy. Eighty
      consecutive obstetric patients, over a one year period who required general
      anaesthesia for caesarian section were evaluated using five bedside tests viz:
      Mallampati test, Thyrometal distance, Sterno-mental distance, Horizontal length
      of the Mandible and Inter-incisor gap. Eight patients had difficult laryngoscopy
      (10%). Mallampati test had a sensitivity, specificity and positive predictive
      value of 87.1%, 99.6% and 70% respectively. The values obtained for the Thyro
      mental distance were 62.5%, 93.1% and 50% respectively. The other tests were not
      able to predict intubation difficulty significantly. When all tests were
      combined, sensitivity, specificity and positive predictive were values 100%,
      36.1% and 14.8%. The combination of Mallampati and Thyro-mental distance had
      values of 100%, 93.1% and 61.5%--sensitivity, specificity and positive predictive
      value. Mallampati can be used as the sole predictor of difficult intubation in
      Nigerian obstetric patients.

PMID- 15171526
TI  - Soap induced urethral pain in boys.
AB  - OBJECTIVE: To describe the cause, possible pathogenesis and management of
      "idiopathic" urethral pain in boys. PATIENTS AND METHOD: Eighteen boys presenting
      with distal urethral pains over a period of 12 years were reviewed and their
      responses to the application of bland petroleum jelly to the external urethral
      meatus before each soap bath was noted. RESULTS: The symptoms started suddenly
      while bathing with soap. Penile erections at onset occurred in 14 (78%). Two
      (11%) had purulent urethral discharge and 1 (5.5%) had meatal stenosis.
      Application of bland petroleum jelly to the external urethral meatus before each
      soap bath satisfactorily controlled the urethral pains. CONCLUSION: "Idiopathic
      urethral pain in boys" may be due to soap induced chemical urethritis and
      responds well to application of bland petroleum jelly to the external urethral
      meatus before each soap bath with appropriate antibiotics when there is
      associated purulent urethral discharge.

PMID- 15171525
TI  - Motorcycle limb injuries in a developing country.
AB  - BACKGROUND: Motorcycles have become a very popular means of transportation in
      Nigeria. This paper is a hospital based study of limb injuries resulting from
      motorcycle accidents in an urban centre in Nigeria. METHOD: All patients
      reporting to the emergency department of the Obafemi Awolowo University Teaching
      Hospitals Complex, Ile-Ife with limb injuries resulting from motorcycle accidents
      between June 1998 and May 1999 were selected for this prospective study. RESULT:
      One hundred and fifteen (79.3%) out of the 145 victims of motorcycle accidents
      that reported to the hospital had injuries involving their limbs. The Male:
      Female ratio was 2.8:1. The mean age was 31.9 +/- 16.7 (S. D.) years, and 20-29
      years; the most commonly involved age group. 42.2% were due to collision with
      automobiles, 22% pedestrian while 8.7% were collisions between motorcycles. The
      use of protective/safety devices was practically non-existent. Seventy-six
      (66.1%) patients had lower limbs injuries, 25 (21.7%) patients had upper limb
      injuries while the remaining 14 (12.2%) injured both upper and lower limbs. The
      tibia was the most commonly fractured bone (32 patients, 27.8%) followed by the
      femur (25 patients, 21.7%). Eighty-six patients (74.8%) with fractures were
      managed by close reduction and splinting. Eighteen (15.7%) patients had internal
      fixation. CONCLUSION: Motorcycle accident is an important cause of limb injuries
      in the developing worlds. Motorcyclists need to be encouraged to use
      protective/safety devices.

PMID- 15171527
TI  - Computed tomographic evaluation of Pott's disease in Accra.
AB  - BACKGROUND: Radiological investigations are central in the diagnosis and
      management of TB spine. In Ghana there is a dearth of literature on the disorder.
      This paper seeks to describe the CT features of the bony and soft tissue changes
      in Pott's disease. METHOD: It is a descriptive report of the CT scans performed
      on 30 patients with proven Pott's disease from January 1998 to December 2000 at
      the Korle Bu Teaching Hospital Accra, Ghana. RESULTS: The disorder was common
      among children and young adults (76.7%). Chronic back pain was the frequent
      presenting complain (53.3%). The dorsal spine remains the site of preference
      while T11 recorded the highest incidence (73.3%). The vertebral body was
      destroyed in all the cases and the fragmentary type of bone destruction was the
      common observation. The incidence of cord compression demonstrated by CT was high
      (73.3%). Other findings were paraspinal and epidural masses observed in (66.7%)
      and (73.3%) respectively. CONCLUSION: CT images demonstrated the spinal level of
      destruction. Improved resolution also showed detailed changes within the outlined
      soft tissue masses, facilitating early diagnosis and prompt initiation of
      therapy.

PMID- 15171528
TI  - Intracerebral abscesses: outcome following management in the CT era.
AB  - BACKGROUND: There are no pathognomonic presenting features of intracerebral
      abscesses. Their clinical features could be confused with those of a tumour or
      any other space occupying lesion. STUDY DESIGN: We analyzed the symptoms,
      predisposing factors, diagnostic modalities, prevalent causative microbes,
      management and outcome in 11 patients, for whom complete records were available
      and who were managed for confirmed intracerebral abscess in our Neurosurgical
      Unit from 1996 to 2000 and compared our findings with those from other series.
      RESULTS: In these patients focal neurological deficit was the most common
      clinical feature, trauma was the most predisposing event and Computerised
      Tomography (CT) Scanning remained the most dependable diagnostic tool. In our
      practice, burr hole drainage augmented with a minimum of 4 weeks intravenous
      antibiotics, was the most frequently used treatment modality. CONCLUSION: The
      outcome was satisfactory (ability to return to pre-morbid activities and duties,
      with no disabling neurological deficits) in 72.8% cases. There was one death.
      This modality remains an effective way of treating patients with intracebrebral
      abscess.

PMID- 15171529
TI  - Computed tomography (CT) in civilian gunshot head injuries in Ibadan.
AB  - BACKGROUND: There is data on civilian gunshot injuries in Nigerians. The purpose
      of the study is to describe the Computed Tomography findings of civilian gunshot
      injuries (GSI) to the head in Ibadan, Nigeria. METHOD: This is a retrospective
      study of Computed Tomography (CT) films and clinical records of 28 consecutive
      civilian gunshot injuries to the head from 1996 to 1999. RESULTS: The gunshot
      injuries to the head were mostly armed robbery related. Though there was a steady
      annual increase of civilian gunshot injuries during the study period, a low CT
      Scan frequency (0.61%) was recorded. The following CT findings were present in
      all the patients; bullet fragments, intraparenchymal haemorrhage, vault fractures
      and soft tissue swelling. The resting position of the bullets showed a
      predilection for the parietal lobe (32.1%) and the most common fracture site was
      also the parietal bone (42.8%). CONCLUSION: CT findings simplified the management
      of civilian gunshot injuries to the head in the patients studied by demonstrating
      the exact pathology sequel to the injury. Despite important constraints, CT
      remains a cost effective means of managing GSI to the head.

PMID- 15171530
TI  - Cryptorchidism in a local population in Nigeria.
AB  - OBJECTIVE: To screen for undescended testis, retractile testis and other anomaly
      of the external genitalia in randomly selected Nursery/Primary schools in Osogbo,
      Nigeria. DESIGN: A prospective study involving seven different Nursery/Primary
      schools with 1615 male pupils ages 2-10 years were screened. SETTING: Five
      private Nursery/Primary schools and two government owned primary school in
      Osogbo. METHODOLOGY: Permission was sought from the schools' Headmasters through
      the proprietors of the private schools, Local inspector of Education of
      government primary schools, and the ethical committees of the University and the
      Teaching Hospital Male pupils were examined by three groups made up of a
      consultant and a resident in each group. RESULTS: A total of 1615 male pupils
      were examined out of which 40 pupils (2.5%) were found to have undescended
      testis, five of these (12.5%) had bilateral cryptorchidism. Eighteen had right
      undescended testis (45.0%) while seventeen (42.5%) presented with left
      undescended testis. Four pupils had retractile testis two on each side and
      another four had a co-existing hydrocoele with their undescended testis.
      CONCLUSION: Prevalence of Cryptorchidism in the age group in this study is
      significant. There is need to screen male children so that early detection and
      correction may be effected.

PMID- 15171531
TI  - Pattern of skin surface lipids in some south-western Nigerians with acne
      vulgaris.
AB  - Unanswered questions still exist regarding pathophysiology of acne vulgaris
      generally and particularly in this environment. METHODS: Skin surface lipid (SSL)
      samples were collected by the heptane sponge technique from faces of 20 Nigerians
      with facial acne vulgaris and 25 controls. The subjects were classified into mild
      and moderately severe acne groups. Total cholesterol and triglycerides were
      determined and expressed in percentage (%) while Undetermined Skin Surface Lipids
      (USSL) (free fatty acids + squalene + wax ester + diglycerides) were computed.
      RESULTS: Triglycerides and total cholesterol levels were significantly higher in
      subjects with acne vulgaris compared with controls (p < 0.001 and p < 0.029
      respectively). There was a progressively significant increase in triglycerides
      from control, though mild to moderately severe acne vulgaris subjects (P < 0.01)
      in all cases. In contrast there was a significant progressive decrease in USSL
      among the three groups (P < 0.001) in all cases. No significant difference was
      evident for all the values on comparison of female subjects with male subjects.
      There were however, significant increases in triglycerides and significant
      decreases in USSL levels for both male and female subjects with acne vulgaris
      compared with their respective controls (P < 0.02, P < 0.01, P < 0.03 and P <
      0.014). CONCLUSION: Alterations in composition of SSL may in part be the
      pathophysiological basis of inflammatory acne vulgaris. Severity of the disorder
      appears to parallel triglyceride level but there was no association with sex.
      Triglycerides and total cholesterol levels are lower in SSL in this environment
      compared with hotter climates.

PMID- 15171532
TI  - Intra-rator variability of primary care physicians in management of
      hyperlipidaemia.
AB  - BACKGROUND: Recent studies support the link between hyperlipidaemia and increased
      prevalence of cardiovascular diseases (CVDs). In Saudi Arabia, CVDs became a
      serious problem following rapid urbanization. The health care system in Saudi
      Arabia makes the primary care accessible to all. AIM: To assess the ability of
      primary care physicians to be consistent with themselves in the management of
      hyperlipidaemia. DESIGN OF THE STUDY: Cross-sectional. SETTING: Family medicine
      department affiliated with tertiary hospital. METHOD: Using 63 patient problem
      vignettes, each physician was asked, whether a patient required no treatment,
      dietary or drug treatment. Exact vignette cases were shown again to each
      physician two weeks later. The Kappa statistical test was used to measure the
      physician's intra-rator variability. RESULTS: Forty-seven physicians were
      recruited to participate in this study. The Kappa statistics suggested an
      excellent intra-rator agreement by only four physicians, but a large majority, 28
      physicians (62.2%) had fair to good agreement while thirteen physicians (28.9%)
      had poor agreement with themselves. CONCLUSION: It is suggested that doctors must
      undergo adequate training and continuous evaluation of their skills in the
      management of hyperlipidaemia. Use of vignettes, might be a good method in
      assessing continuous medical education.

PMID- 15171533
TI  - Negative appendicectomy rate at the U. I. T. H. Ilorin, Nigeria.

PMID- 15171534
TI  - Heart failure complicating tetralogy of Fallot.
AB  - BACKGROUND: Heart failure is considered to be an unusual complication of
      uncorrected tetralogy of Fallot. PATIENTS AND METHOD: Three adolescents with
      tetralogy of Fallot, presenting in congestive cardiac failure are presented. Two
      died. Myocardial infarction was found in the only patient that underwent autopsy,
      and is thought to be an important aetiological factor in the development of the
      heart failure in the patients. CONCLUSION: The cases presented illustrate the
      fact that heart failure complicating tetralogy of Fallot may not be as uncommon
      as was previously thought to be the case, especially in older children. There is
      a need for early diagnosis and expeditious institution of appropriate management
      before such complications occur.

PMID- 15171535
TI  - Thoracic myelocystomeningocele in a neurologically intact infant.
AB  - OBJECTIVES: To report an uncommon and a rare case of a high congenital spinal
      anomaly with an unusual presentation. METHODS: This is a case presentation with
      relevant radiological and operative findings. CONCLUSION: This lesion is a
      differential diagnosis of cystic congenital spinal mass lesions. This case is an
      example of a high congenital spinal lesion with very minimal or negligible
      neurological deficits, with no other congenital malformations.

PMID- 15171537
TI  - Beliefs, perceptions and psychological impact of acne vulgaris among patients in
      the Assir region of Saudi Arabia.
AB  - BACKGROUND: There is a paucity of reports in the literature detailing the
      assessment of the beliefs, perception and psychological impact of acne patients.
      This is the first study from Saudi Arabia designed to address this issue.
      MATERIALS AND METHODS: A voluntary self-completed questionnaire was used to
      collect data from acne patients visiting a community-based hospital in Assir
      region of Saudi Arabia. DATA COLLECTED, INCLUDED: patients biodata, duration and
      severity of the disease before the presentation, source of knowledge,
      psychological impact, and medication preference. The findings were compared to
      those of developed countries. RESULTS: 130 patients completed the questionnaires.
      Females were more affected than males (71.5%, 28.5% respectively). The M:F ratio
      was 1:2.5. Males tend to present with more severe form of the disease. Most
      patients had the disease for more than 1 year at presentation. Most patients
      sought medical advice as a self-made decision. Doctors were the most common
      source of information to patients. Most patients believe that hormonal imbalance
      and dirt were the major cause of acne while most of them believed that stress and
      diet were the major exacerbating factors. The most significant psychological
      impact in acne patients was on their self image which was severe in 49% of the
      patients, while the most bothering symptom was the spot of acne lesion. Most
      patients had used skin cleansers and creams before seeking medical advice (46.1%,
      31.5% respectively). Retinoids and antibiotics were the most known prescribed
      medications to acne patients. Most acne patients expressed no preference of
      medication, but most of those who did so preferred topical medication.
      CONCLUSIONS: No major differences were found in the beliefs, perception and
      psychological impact of acne patients from a developing society compared to more
      developed societies. More community-based and developmental programmes are needed
      to upgrade the knowledge and common beliefs of acne patients.

PMID- 15171538
TI  - An unusual presentation of congenital bronchoesophageal fistula.
AB  - We present the case of a 5-week-old neonate with multiple congenital
      abnormalities including a broncho-oesophageal fistula, which showed radiological
      features suggestive of congenital diaphragmatic hernia. Emergency limited barium
      swallow done was initially reported as a case of diaphragmatic hernia. Autopsy
      revealed pus within the right lung, and a fistulous connection between the
      oesophagus and an intralobar sequestrated lung. No diaphragmatic hernia or intra
      abdominal organ abnormality were seen, and an occipital meningomyelocoele was
      also confirmed.

PMID- 15171536
TI  - Traditional bonesetters in south western Nigeria--friends or foes?
AB  - OBJECTIVE: To highlight the dangers inherent in the practice of traditional bone
      setting in south western Nigeria as evidenced by the preventable complications
      that accompany treatment of fractures, joint dislocations and limb deformities by
      traditional bonesetters (TBS). METHOD: Twenty-five consecutive patients with
      fractures, dislocations and limb deformities who had been previously managed by
      TBS and who subsequently presented to the University College Hospital, Ibadan (on
      account of complications from treatment at the TBS) between 15 October 1999 and
      31st March 2000 were evaluated. RESULT: Fourteen patients had fracture non-union
      or malunion necessitating open reduction and internal fixation. Two patients with
      wet gangrene of the extremities had amputations. CONCLUSION: Traditional bone
      setting is an ancient trade practiced in Nigeria and most developing countries
      without government regulations and they lack guidance. The complications that
      accompany these practices are unacceptable and it is imperative that there should
      be legislation to curb their activities and save the unsuspecting public from
      further harm or even death.

PMID- 15171539
TI  - Recurrent respiratory papillomatosis mimicking retropharyngeal abscess in a
      Nigerian child.
AB  - Recurrent respiratory papillomatosis (RRP) is not an uncommon disease of the aero
      digestive tract, usually involving points of narrowing. Involvement of the
      oropharynx, particularly when florid, may be easily confused with a
      retropharyngeal abscess. STUDY DESIGN: Case report of a 1 1/2 year-old child with
      florid pharyngeal RRP. RESULTS: The clinical presentation and features on
      radiography of this patient mimicked retropharyngeal abscess. The patient
      successfully had a preoperative tracheosomy and excision of the RRP. CONCLUSION:
      There was a diagnostic dilemma in this patient because of the identical features
      of the two conditions. A high index of suspicion and painstaking, careful
      clinical and radiological evaluation is the key to diagnosis and prompt
      definitive management.

PMID- 15171540
TI  - Arrow injury to the skull base.
AB  - An unsual case of penetrating nasal injury with middle skull base involvement,
      from fired arrow is reported. The arrow was surgically removed and the patient
      remains well with no sequelae. We therefore present this case because of its
      rarity. The anatomical principles underlying the surgical management of the
      lesions are discussed.

PMID- 15171541
TI  - [Research progress on Alzheimer's disease: pathogenesis and medical therapy].
AB  - Alzheimer's disease (AD) is a common disease in elder people. Its incidence rate
      is about 5% in people above 60 years old. It has become an important factor that
      seriously impacts the development of families and society, and caused wildly
      attention all over the world. In this article, we discuss the mechanisms of AD in
      four aspects and put forward the strategies of drug therapy.

PMID- 15171542
TI  - [Morphological and quantatitive capillary changes in aging human brain].
AB  - OBJECTIVE: To investigate morphological changes of capillary in aging brain and
      explore the role of vascular factor in brain aging. METHODS: Twenty-eight brains
      of individuals (mean age 65 years) who died without clinical or pathological
      involvement of nervous system and 6 brains of Alzheimer's disease (AD) patients
      (mean age 83 years) were obtained at autopsy. Sections from frontal lobe,
      occipital lobe, striatum and hippocampus of normal subjects and sections from
      hippocampus of AD patients were used for hematoxylin eosin (HE), lox fast blue
      (LFB), toluidine blue stains and ulex europaeus agglutinin (UEA) immunostaining.
      After observations of morphological changes of neuron and capillary, computer-aid
      image analysis was performed to quantify numerical density and area density of
      neuron and capillary in frontal lobe, occipital lobe, putamen, CA3 sector of
      normal subjects and CA3 sector of AD patients. Numerical ratio and area ratio of
      neuron and capillary were then calculated. Correlations between neuron/capillary
      ratio and age were estimated using Pearson's correlation test. Difference of
      neuron/capillary ratio in CA3 sectors between AD patients and advanced aged
      normal subjects (> 75 years) was analyzed with Student's t-test. RESULTS: Several
      pathological microvascular changes, including increased tortuosity, looping,
      bundling, stringing, and effacement of endothelia were seen in aged subjects and
      more prevalent in AD patients. Numerical ratio and area ratio of neuron and
      capillary of frontal lobe, occipital lobe and putamen significantly increased
      with age in normal aging subjects. CONCLUSIONS: Morphological changes and
      relative decrease in number and capacity of capillary in aging brain may reduce
      cerebral blood flow and metabolism, and consequently result in functional
      impairment of aging brain. Vascular factors may play an important role in the
      development of brain aging.

PMID- 15171543
TI  - [Estrogen receptor alpha and colocalization of Bcl-2 in hippocampus of
      Alzheimer's disease].
AB  - OBJECTIVE: To investigate the possible mechanism by which estrogen regulates
      apoptosis through the estrogen receptor. METHODS: By means of fluorescence
      immunocytochemistry, the present study investigated the distribution of Bcl-2 and
      the colocolization of Bcl-2 and ERalpha immunoreactivity in the hippocampus of 10
      Alzheimer's disease (AD) patients and 10 aged controls. RESULTS: Bcl-2
      immunoreactivity was widely distributed in neurons, concentrating predominantly
      on the subfields CA3 and CA4 in the stratum pyramidale of hippocampus both in
      controls and in AD patients. Bcl-2 staining in the labeled neuron was observed
      mainly in the cytoplasm and neuritic processes, but a few nuclei were also
      positive. Bcl-2 labeling was also detected in the astrocytes mainly in AD, but
      sparsely in controls. Double-labeled fluorescence immunocytochemistry showed that
      most Bcl-2-immunolabeled neurons also exhibited positive staining for ERalpha.
      CONCLUSIONS: Estrogen may function as a regulator of apoptosis to modulate the
      expression of Bcl-2 in neurons and astrocytes in hippocampus of AD through
      ERalpha.

PMID- 15171544
TI  - [Association between Alzheimer's disease and nitric oxide synthase III
      polymorphism].
AB  - OBJECTIVE: To explore the association between Alzheimer's disease (AD) and nitric
      oxide synthase (NOS) III in Chinese Han population. METHODS: Seventy-five AD and
      68 normal controls were genotyped for NOS III G894T polymorphism. Genotyping was
      carried out by PCR-RFLP methods. RESULTS: There were two genotypes of NOS III, GG
      and GT, in either AD patients or normal controls. The frequencies of these two
      genotypes were 78.7% and 21.3% in AD patients and 82.4% and 17.6% in normal
      controls, respectively. No association was found between AD and NOS III genotype
      (P > 0.05). There were two alleles, G and T, in AD patients and normal controls.
      The frequencies of these two alleles were 89.3% and 10.7% in AD patients and
      91.2% and 8.8% in normal controls, respectively, indicating that there was no
      association between AD and NOS III allels (P > 0.05). CONCLUSIONS: There was no
      association between AD and NOS III G894T polymorphism in Chinese Han population.

PMID- 15171545
TI  - [A caregiver survey in Beijing, Xi'an, Shanghai and Chengdu: health services
      status for the elderly with dementia].
AB  - OBJECTIVE: In order to rationally allocate resources and to improve the quality
      of life of people with dementia, it is necessary to assess their current health
      services status. METHODS: A population-based door-to-door caregiver survey was
      conducted in Beijing, Xi'an, Shanghai and Chengdu in 1998. Totally 1 141
      individuals with dementia were found among 34 807 residents aged 55 years and
      over on the basis of national prevalence study of dementia. Then 428 families
      with demented patients were randomly selected for questionare interview.
      Interviews were completed in 405 but refused by 23 families. Measurements
      included demographic characteristics of patients and their caregivers,
      perspective of the victim of the disease, current awareness of the disease and
      medical and welfare services provided. RESULTS: Among 405 cases of dementia
      (including 298 cases of AD and 81 cases of VaD), mean MMSE scores were 16.3 +/-
      5.3 for 157 mild cases, 12.7 +/- 5.4 for 135 moderate cases, and 6.2 +/- 5.8 for
      110 severe cases. Most patients (96%) were cared for at home by family members.
      Among caregivers, 189 (48.8%) considered the impairment of cognition, behavior
      and daily living activity in demented persons as a result of normal aging. Half
      of the caregivers spend over 8 hours each day looking after the patient. Whether
      the caregivers brought their relatives with dementia to a doctor was determined
      by disease severity, i.e. 8.3% for mild, 13.5% for moderate, and 19.4% for severe
      in 1996 to approximately 1997 and 14.4%, 25.6% and 33.6%, respectively in 1998
      1999. Of those, only 26.9% reported receiving a dementia diagnosis, and only
      21.3% received a recommedation to take medication. However, there was no
      established standard treatment and only 2% patient's used Ache-I. CONCLUSIONS:
      General education is needed to increase the public awareness of dementia. For
      patients with dementia, early diagnosis, early treatment and optimal care are
      important to improve their quality of life.

PMID- 15171546
TI  - [Comparative study on the clinical features of Alzheimer's disease and vascular
      dementia].
AB  - OBJECTIVE: To investigate the clinical features of Alzheimer's disease (AD) and
      vascular dementia (VaD), and to find effective methods for differential diagnosis
      between the two entities. METHODS: Totally 112 AD patients and 92 VaD patients
      were enrolled in this study, consisted of patients from the memory clinics and
      patients from the community population visited during the epidemiological survey
      from 1996 to 2000. Diagnosis of dementia, probable AD and probable VaD were made
      according to international criteria. Results of specific neuroimaging examination
      were referred to verify the diagnosis and the final diagnosis of each patient was
      determined from the discussion between clinical experts and radiological
      professionals. Analysis on clinical and neuroimaging data was performed, aiming
      at finding differential points between the two dementia-subtypes. A logistic
      binary multiple regression analysis was performed to pick out those statistically
      significant clinical features for differential diagnosis at last. RESULTS: AD and
      VaD patients have different clinical features in various demented stages,
      therefore the indexes that differentiate the two dementia subtypes change
      accordingly. The predominant features of mild AD appear to be deficits of
      prolonged memory and learning ability, while the major impairment of mild VaD
      patients is decline of calculating ability. With the progress of dementia,
      learning ability and attention turn to be the effective indexes for differential
      diagnosis. In the mild and moderate demented stage, AD patients are inferior to
      VaD patients in handling finacial affairs and making phone calls, while VaD
      patients often degenerate in daily activities concerning with both physical
      ability and intellectual level. Severe VaD patients appears more global
      degeneration of living ability compared to AD patients. The difference of ADL
      scores between the two subtypes is significant in moderate to severe demented
      patients (P < 0.05). Psychological behavior symptoms, such as repeatedly
      collecting useless things, are the characteristic manifestation to differentiate
      AD from VaD in all clinical stages. CONCLUSIONS: The results of our study
      indicate that substantial differences exist between AD and VaD patients. Such
      differences can be attributed to the differences of lesion nature and
      distribution, as well as the underlying pathophysiological procedures of each
      disease.

PMID- 15171547
TI  - [Memory-assessing methods which help the clinical diagnosis of early Alzheimer's
      disease].
AB  - OBJECTIVE: To evaluate distribution and influence factors of logic memory (LM)
      modified in assessing and scoring method in normal population and Alzheimer's
      disease (AD) patients, and definite the cut-off point of the modified scale.
      METHODS: Totally 183 AD patients, including 118 mild and 65 moderate in degree,
      1,417 controls, including 1,283 normal individuals and 134 individuals suffered
      from other diseases, were recruited in this study. Modified LM was conducted.
      RESULTS: Educational level (F=354.36, STB=0.46, P=0.0001) was the most obvious
      factor in demographic data to influence total score in normal control group by a
      fitting of multiple regression models. The total score increased with the rising
      of educational level in normal controls (P=0.0001) and other diseases controls
      (P=0.0001), but not in AD cases (P=0.1365). The total scores were significantly
      different among normal controls (20.2 +/- 0.2), other diseases controls (17.5 +/-
      0.5), mild AD patients (9.6 +/- 0.5) and moderate AD patients (7.1 +/- 0.7)
      (P=0.0001, P=0.0059), after adjusted educational level, age, sex and rural/urban
      status by multiple analysis covariance. The sensitivity of cut-off points using
      modified methods to diagnose AD reasonably increased to 71.98%, while the
      specificity was 94.11%. According to the sum of long-delayed recall and long
      delayed recognition, the sensitivity increased with the rising of educational
      levels. For education levels at illiteracy, elementary school, junior middle
      school, senior middle school and above senior middle school, the cut-off points
      for total score of modified method were 6.5, 9.5, 10.8, 13 and 15.8,
      respectively, and for sum of long-delayed recall and long-delayed recognition the
      cut-off points were 5, 6, 8, 9, 10. CONCLUSIONS: When modified LM used as a
      neuropsychological assessment, it is with high specificity, high accuracy and
      reasonable sensitivity. It is suitable for the diagnosis of AD in early stages,
      especially for individuals with high educational levels.

PMID- 15171548
TI  - [Relationship between the data from MR-diffusion tensor imaging and the clinical
      cognitive evaluation in Alzheimer's disease].
AB  - OBJECTIVE: To determine the relationship between the extent of the damage and
      clinical data in Alzheimer's disease (AD). METHODS: Twenty-two patients with AD
      and twenty-two controls received MR-diffusion tensor scanning. The fractional
      anisotropy (FA) values of white matter in AD patients were measured respectively
      in parietal lobe and the genu of corpus callosum. Independent-samples t-test for
      non-paired data was used to test differences between AD and controls for FA
      values. Correlation analysis was applied to reveal the correlations between FA
      values in each region and the MMSE, FOM, RVR, BD and DS scores. RESULTS: Positive
      correlations were found between FA values in left parietal lobe and FOM/DS, and
      between FA values in genu of corpus callosum and MMSE scores. CONCLUSIONS: In AD,
      the MR-DTI can reflect the relationship between the degree of white matter
      abnormalities and the cognitive impairment.

PMID- 15171549
TI  - [Isolation and cloning of genes related to growth inhibition of human glioma
      BT325 by EGF].
AB  - OBJECTIVE: To isolate and clone the differentially expressed genes induced by
      epithelial growth factor (EGF) with inhibiting dosage in cultured glioma BT325
      cells and understand the molecular mechanism that inhibits glioma cells growth.
      METHODS: Using differential display reversed transcription polymerase chain
      reaction (DDRT-PCR) method to analyze the differentially expressed cDNA in BT325
      cells induced by EGF with inhibiting dosage. After sequencing and homology
      research, the differentially expressed cDNA fragments were further confirmed by
      Dot blot analysis and one of them by Northern blot. RESULTS: Up-regulated genes
      cDNA fragments were isolated in growth inhibited BT325 cells. It was found that
      five cDNA fragments were highly homologous to the known human genes, while one
      was a fragment of a novel genes. Among these genes, one has coding sequence
      homology with transaldolase (TAL), which has been proved to be associated with
      apoptosis in recently research. CONCLUSIONS: High-dose EGF could change the
      expression of many genes in BT325 cells. EGF can inhibit the growth of BT325 cell
      growth, which may be resulted from its potential role in promoting TAL gene
      expression and thus inducing cell apoptosis.

PMID- 15171550
TI  - [Molecular design and biological activity of BCR-ABL tyrosine kinase inhibitors].
AB  - OBJECTIVE: To discover BCR-ABL tyrosine kinase inhibitors through structure based
      virtual screening. METHODS: Docking screening against the distinctive inactive
      conformation of the catalytic domain of BCR-ABL tyrosine kinase was performed on
      3D database. The MTT assay was performed to assess the viability of the tumor
      cells treated with selected compounds. The amount and kinase activity of BCR-ABL
      protein were detected in the presence of compounds by Western blot analysis and
      immunoprecipitation. RESULTS: From the top 1,000 compounds with the best DOCK
      energy score, 15 compounds were selected for biological assay. Eight out of 15
      compounds showed notable inhibitory activity against Ph+ human K562 cells with
      IC50 values ranging from 10 to 200 micromol/L. In cell-based assays of ABL
      tyrosine phosphorylation, the ability of two kinds of novel, structurally
      diverse, lead compounds to inhibit ABL kinase activity was observed. However, no
      significant differences in the amount of BCR-ABL protein were noted on the ABL
      immunoblot in the presence of these lead compounds. CONCLUSIONS: Two promising
      lead compounds were discovered to inhibit BCR-ABL tyrosine kinase activity.
      Virtual screening technique has been proven to narrow down the size of screening
      compound libraries to the most prospective drug candidates with high success
      rates.

PMID- 15171551
TI  - [Identification and analysis of expressed sequence tags related to K562 cells
      into erythroid differentiation].
AB  - OBJECTIVE: To isolate expressed sequence tags (ESTs) related to K562 cells
      erythroid differentiation. METHODS: Modified differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) method was applied to identify
      differential ESTs in uninduced and induced K562 cells by HEMIN for 36 hours.
      Remarkable differential ESTs were firstly selected for cloning, sequencing and
      bioinformational analyzing. Several ESTs representing new sequence or providing
      functional clue were selected for Northern blot analysis. RESULTS: Sixty
      differentially expressed cDNA fragments related to K562 cells inducted into
      erythroid differentiation by HEMIN were obtained. Among them, 38 were upregulated
      and 22 downregulated. Among the 40 differential ESTs selected for cloning,
      sequencing and bioinformationally analyzing, 23 were found to match to known
      GenBank sequences and 10 represented cDNA sequences with only dbEST database
      matches and 7 ESTs have no any database matches. The results of 6 in 8 ESTs
      selected for Northern blot analysis were shown to be consistent with the
      differential expressions of DDRT-PCR. CONCLUSIONS: The improved DDRT-PCR method
      had successfully overcome the problem of false positive. These ESTs provide some
      clue for studying the molecular mechanisms and regulation network of erythroid
      differentiation.

PMID- 15171552
TI  - [Immunogenecity of combined hepatitis A and B vaccine].
AB  - OBJECTIVE: To observe the immunogenicity of combined hepatitis A and B vaccine
      (HAB). METHODS: The combined HAB vaccine was prepared and different
      concentrations of HAB were administered on mice in week 0, 4 and 24, and then we
      tested the antibodies to both hepatitis A virus and B virus. After the first
      injection, we tested the hepatitis A antigen-induced and hepatitis B surface
      antigen-induced stimulation indices in spleen monocyte as well as changes of CD4+
      and CD8+ cell numbers. RESULTS: The serum antibody positive rates were 100% in
      all three groups, and the antibody induced by HAB vaccine were earlier than by
      monovalent vaccine. The hepatitis A antibody and hepatitis B surface antibody
      titers after the combined vaccine inoculation were not significantly higher than
      those after the monovalent vaccine inoculation. On the other hand, after the
      first injection of the combined vaccine, the hepatitis A antigen-induced and
      hepatitis B surface antigen-induced stimulation indices in spleen monocyte were
      detected. The numbers of CD4+ and CD8+ cells increased. CONCLUSIONS: HAB vaccine
      has reliable immunogenicity.

PMID- 15171553
TI  - [A cumulative renal survival analysis of 495 cases of IgA nephropathy].
AB  - OBJECTIVE: To study the long-term outcome of idiopathic IgA nephropathy and
      analyze its clinical and histological prognostic factors. METHODS: We conducted a
      retrospective analysis of 495 cases of IgA nephropathy patients in our hospital
      from 1986 to 2002. Renal survival was analyzed by Kaplan-Meier method, univariate
      analysis and multivariate Cox regression analysis. RESULTS: The cumulative renal
      survival rate was 85% at 10 years and 70.9% at 15 years. Univariate analysis
      found the following parameters at the time of biopsy to be significantly
      correlated with poor renal survival: serum creatinine > or = 133 micromol/L (P <
      0.001), hypertension (P < 0.05), 24-hour urine protein excretion > or = 3 g (P <
      0.001), histological subclass V (P < 0.001), and without the history of gross
      hematuria (P < 0.05). The Cox regression analysis showed that only the presence
      of hypertension (HR=7.75, 95%CI 1.02 to approximately 2.19) and serum creatinine
      level (HR=1.49, 95%CI 1.54 to approximately 38.90) were independent prognostic
      indicators. CONCLUSIONS: The findings in Chinese IgA nephropathy patients are in
      agreement with the results of many other studies worldwide.

PMID- 15171554
TI  - [Expressive level of vascular endothelial growth factor in peripheral blood in
      patients with pituitary adenomas].
AB  - OBJECTIVE: To discuss whether vascular endothelial growth factor (VEGF) in the
      peripheral blood can reflect the biological activities of pituitary adenomas.
      METHODS: The concentrations of VEGF in peripheral blood were measured with ELISA
      in 203 patients with pituitary adenomas, 22 patients with pituitary hyperplasia,
      7 patients with pituitary Rathke' pouch and 3 patients with pituitary abscess.
      RESULTS: The serum VEGF levels were (366.8 +/- 211.1) pg/ml and (286.8 +/- 107.6)
      pg/ml in patients with pituitary adenomas and pituitary hyperhasia, respectively,
      which were higher than those in patients with pituitary Rathke' pouch [(180.5 +/-
      61.7) pg/ml], patients with pituitary abscess [(147.5 +/- 46.3) pg/ml] and the
      health control [(180.8 +/- 56.2) pg/ml] (P < 0.05). In patients with pituitary
      adenomas, the VEGF levels were (380.0 +/- 234.5) pg/ml in macroadenomas and
      (380.1 +/- 2870.3) pg/ml in giant adenomas, higher than those in microadenomas
      [(294.6 +/- 111.6) pg/ml] and in pituitary hyperhasia respectively (P < 0.05).
      The serum VEGF levels were not significantly different in pituitary adenoma in
      terms of invasive growth, apoplexy, cyst and hormone secretory functions (P >
      0.05). CONCLUSIONS: The upregulation of serum VEGF expression may reflect the
      biological activities of pituitary adenoma. However, it may not be associated
      with pituitary Rathke' pouch, pituitary abscess, adenoma with invasiveness,
      apoplexy, cyst and hormone secretory function. The serum VEGF levels could be
      helpful in differentiating pituitary adenoma from pituitary Rathke' pouch and
      pituitary abscess.

PMID- 15171555
TI  - [Effects of nasal continuous positive airway pressure on serum leptin
      concentration and the metabolic parameters in obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To evaluate the effects of nasal continuous positive airway pressure
      (nCPAP) on serum leptin concentration and the metabolic parameters in patients
      with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: Serum leptin
      levels and true insulin (TI) levels were measured before and after one night
      nCPAP therapy in 18 patients. Eight patients received regular nCPAP treatment and
      had no change of body weight (BMI change < or = 1.5 kg/m2 from baseline) were
      recruited to the reassessment study 7.5 months after therapy. RESULTS: After one
      night use of nCPAP, there was a significant decrease in serum leptin [(8.47 +/-
      0.62) microg/L vs (7.32 +/- 0.64) microg/L, P = 0.022] without change in other
      parameters. After 7.5 months of nCPAP treatment, serum leptin levels continued to
      decrease significantly without changes in BMI [(8.35 +/- 0.83) microg/L vs (6.05
      +/- 0.78) microg/L; P = 0.036), and fast blood glucose (FBG) and true insulin
      (TI) also decreased significantly (P = 0.036) in OSAHS patients. However,
      triglyceral (TG) and cholesterol (Chol) maintained the pretreatment level (P >
      0.05). CONCLUSIONS: OSAHS may have significant effects on the serum leptin levels
      and the correction of sleep disordered breathing by nCPAP can reduce the serum
      leptin levels. Decrease of leptin was independent of BMI change. The glucose
      metabolic disturbance and insulin resistance in OSAHS were improved after 7.5
      months of nCPAP treatment.

PMID- 15171556
TI  - [Propylthiouracil-induced overt hepatic injury in patients with hyperthyroidism].
AB  - OBJECTIVE: To study the incidence, clinical features and related factors of
      propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.
      METHODS: A prospective study were carried out in 70 patients of hyperthyroidism
      with normal liver function. Every patient was treated with PTU 300 mg/d until the
      thyroid functions recovered to normal, following by decease and maintenance PTU
      dose in period of six months. Liver function, including serum levels of alanine
      aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase
      (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function
      (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and
      thyrotropin) and blood routine items were measured before therapy and once a
      month for six months after PTU therapy was begun. RESULTS: Sixty-four cases of 70
      patients completed the therapy for 6 months. Hepatic injury developed in 33
      patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients
      (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt
      hepatic injury in 5 patients (7.8%) after PTU administration. However, all the
      patients who developed overt hepatic injury did not stop PTU. Hepatic function
      returned normal one month after stopping PTU. No one finally suffered from viral
      hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic
      injury. CONCLUSIONS: PTU-induced symptomatic hepatic injury is not rare and
      usually develops within the first few months of PTU administration. Its clinical
      course is relatively benign. However, it may be difficult to predict its
      development, so all patients should be monitored for liver function test during
      the administration in early stage.

PMID- 15171557
TI  - [Superovulation and intrauterine insemination in treatment of idiopathic
      infertility in 202 cycles].
AB  - OBJECTIVE: To evaluate the effect of superovulation with recombinant follicle
      stimulating hormone (r-FSH) therapy and intrauterine insemination in the
      treatment of idiopathic infertility. METHODS: Superovulation with r-FSH therapy
      and intrauterine insemination were used in 202 cycles of 88 couples in the
      Department of Obstetrics and Gynecology of Monash Medical Centre. RESULTS: The
      per cycle ovulation rate and in-ovulation rate were 95.7% and 4.3% respectively,
      and the per cycle pregnancy rate was 11.6% with no cases of hyperstimulation. The
      cancelling rate was 7.4% because of the development of multiple follicles. The
      overall cumulative conception rate was 22.7% per patient, with 15% of twin
      pregnancies. There were no differences between pregnancy group and non-pregnancy
      group in age, BMI, treatment days, number of mature follicles, endometrial
      thickness and number of treatment cycles. The only significant parameter observed
      between the two groups was infertility time (P < 0.05), which was longer in non
      pregnancy group [(30.52 +/- 13.08) months] than in pregnancy group [(24.25 +/-
      6.45) months]. CONCLUSIONS: Superovulation and intrauterine insemination is a
      safe and more cost-effective method in treatment of idiopathic infertility.

PMID- 15171558
TI  - [Short-term results of modular extensively porous-coated revision stem in
      revision total hip arthroplasty].
AB  - OBJECTIVE: To evaluate the short-term clinical and radiographic results of
      modular fully porous-coated stem in revision operation of total hip arthroplasty.
      METHODS: From May 2001 to November 2002, ten cases with twelve hips received
      revision total hip arthroplasty using modular Profemur R with fully porous-coated
      stem. There were three males and seven females and the average age was 54.2 years
      (35 to approximately 71 years). The reasons for revision operation included
      aseptic loosing in eleven hips and septic loosing in one hip. All the patients
      were evaluated radiographically and clinically. Radiographic evaluation included
      the classification of bone loss, leg discrepancy, offset and antiversion before
      and after revision and bone in-growth postoperatively. Clinical evaluation were
      based on Harris score system. RESULTS: The average follow-up period is 13.5
      months (range: 6 to approximately 24 months). Leg discrepancy from more than 2 cm
      in six cases were restored to less than 1 cm postoperatively. Femoral offset,
      antiversion angle and neck-shaft angle were also restored to normal limitation.
      All the patients were allowed to full weight-bearing 3 to approximately 5 months
      later and pain relief occurred in all involved hips. At the last follow-up, bone
      in-growth occurred in eleven hips and solid fibrous fixation only in one case.
      Harris score was improved from a mean of 25 to 72. Complications mainly consisted
      of femoral shaft fracture in three cases but no infection or dislocation was
      found postoperatively. CONCLUSIONS: Satisfactory results of short-term
      radiographic and clinical follow-up can be achieved using modular fully porous
      coated stem for revision total hip arthroplasty.

PMID- 15171559
TI  - [Effect of intraoperative using cell saver on blood sparing and its impact on
      coagulation function].
AB  - OBJECTIVE: To observe the effectiveness of using cell saver (CS) during surgery
      on blood sparing and its impact on patient's hematology and coagulation function.
      METHODS: One-hundred and thirty-eight patients undergoing elective surgery were
      recruited for intraoperative blood salvage using CS. Blood routine, blood
      chemistry and coagulation function were measured before surgery, after infusion
      of salvaged blood and postoperative day 1, respectively. RESULTS: In total,
      112,056 ml of packed red blood cells were collected, with a mean value of 812 ml
      per patient. The percentage of autologous blood transfusion volume to the total
      blood transfusion volume was from 48% to 89%. Allogenic blood transfusion rate
      was from 5% to 100%. Compared with the values before surgery, the hemoglobin
      concentration, platelet count, plasma total protein and fibrinogen concentration
      decreased significantly after the transfusion of salvaged blood and the first
      postoperative day (P < 0.05 or P < 0.01), while the prothrombin time was
      significantly prolonged (P < 0.05). CONCLUSIONS: The use of CS during surgery
      can, to a certain extent, reduce the requirement of allogenic blood. However,
      reinfusion of large amount of salvaged blood may affect coagulation function.

PMID- 15171560
TI  - [Quality of methodology and reporting of randomized controlled trials of
      acupuncture for obesity].
AB  - OBJECTIVE: To evaluate the quality of methodology and reporting of randomized
      controlled trials of acupuncture for obesity worldwide. METHODS: Collecting all
      the randomized controlled trials of acupuncture for obesity worldwide by
      systematically searching without language limitation. The quality of methodology
      and reporting was evaluated by the quality criteria recommended by Cochrane
      handbook and CONSORT (consolidate standards of reporting trial) and STRICTA
      (standard for reporting interventions in controlled trials of acupuncture)
      checklists. RESULTS: Seven randomized controlled trials of acupuncture for
      obesity were identified. The quality of methodology was graded as "A" in one
      trial, "B" in two trials and "C" in the other four trials. The reporting quality
      of the seven trials was graded as "C". CONCLUSIONS: The methodology quality of
      the randomized controlled trials of acupuncture for obesity was too poor to
      provide strong evidence for clinical practice, and the poor reporting quality of
      the trials resulted in inadequate information from the trials.

PMID- 15171561
TI  - [Changes of plasma adrenomedullin level during the process from chronic
      bronchitis to chronic cor-pulmonale].
AB  - OBJECTIVE: To investigate the relationship between the plasma adrenomedullin
      (ADM) levels and the extent of chronic cor-pulmonale and its underlying diseases,
      and explore the role of ADM in these diseases. METHODS: Totally 26 patients with
      chronic bronchitis, chronic bronchitis accompanied with obstructive
      pneumonectasia or chronic cor-pulmonale were included respectively as clinical
      test group T1, T2 and T3; 26 normal people and 14 patients with pneumonia were
      chosen as control groups (group C1 and C2). Plasma concentration of ADM in every
      selected individual had been measured with specific radioimmunoassay. RESULTS:
      Levels of plasma ADM in T3 were significantly higher than those in T2, and T2
      than T1, C1 and C2 (P < 0.05), but there were no obvious difference between T1
      and C1, between T1 and C2 (P > 0.05). CONCLUSIONS: Plasma ADM levels can reflect
      the severity of the above series of diseases.

PMID- 15171562
TI  - [Vascular dementia and vascular cognitive impairment].
AB  - Vascular dementia (VaD) subtypes include multi-infarct dementia, subcortical
      ischemic vascular dementia, strategic-infarct dementia, etc. Poststroke dementia
      may be related to preexisting cognitive level, and the frequency increased with
      aging, lower educational level and accompanied vascular risk factors. Vascular
      cognitive impairment (VCI) forms a spectrum that includes VaD, mixed Alzheimer's
      disease (AD) with a vascular component, and VCI without dementia. The concept of
      VCI will improve the early diagnoses and secondary prevention and treatment of
      VaD, and promote the further research on vascular component in neurodegenrative
      disorders.

PMID- 15171563
TI  - [Advances in molecular biology and clinical study of amyloid precursor protein
      for Alzheimer's disease].
AB  - Alzheimer's disease (AD) is the most common cause of dementia in elderly
      population. There are two hallmark pathological lesions: the intracellular
      neurofibrillary tangles (NFTs) and the extracellular amyloid deposits in the
      senile plaques (SP). The NFTs are aggregates of hyperphosphorylated microtubule
      Tau protein. The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides
      Abeta40 and Abeta42. The Abeta peptides are derived from the amyloid precursor
      protein (APP) which is considered very important for the AD pathogenesis. In
      recent years, studies have focused on understanding the generation of Abeta
      peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and
      progression of both familial and sporadic AD (FAD and SAD). This review covers
      the trafficking and processing of APP, the amyloid cascade hypothesis in AD
      pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset
      and late-onset AD. The risk factor apolipoprotein E (ApoE) for AD and therapeutic
      anti-beta-amyloid vaccination strategies for prevention of AD are also discussed.

PMID- 15171564
TI  - [Assessment and intervention on mental burden of the caregivers of dementia
      patients].
AB  - Along with the aging of population, dementia became a social problem disturbing
      our life. Western researches focused on caregivers found that, the more severe
      the dementiais, the more burdens on caregivers. Furthermore, considening the
      different relationship to the patient, different culture background and different
      types of dementia, there are different problems in care. Based on comprehensive
      assessments on the demented and the caregiver, specific health education and
      other assistant services may improve both the mental and physical health of the
      caregivers, and reduce the disease burden due to dementia.

PMID- 15171565
TI  - [Living animal models of the medical shock wave].
AB  - This article reviews the methods, notes and evaluation of the living animal
      models of the medical shock wave, including directly shocked animal models,
      surgical implantation of stones into animal kidney models, implantation of tumor
      cells into animal models and animal bone models. The living animal models play an
      important role in studying the medical shock wave.

PMID- 15171566
TI  - Combined administration of taurine and meso 2,3-dimercaptosuccinic acid in the
      treatment of chronic lead intoxication in rats.
AB  - The present study describes the dose-dependent effect of taurine, an amino acid
      and a known antioxidant, either alone or in combination with meso 2,3
      dimercaptosuccinic acid (DMSA) in the treatment of subchronic lead intoxication
      in male rats. The effects of these treatments in influencing the lead-induced
      alterations in haem synthesis, hepatic, renal or brain oxidative stress and lead
      concentration from soft tissues were investigated. Exposure to lead produced a
      significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD)
      activity, reduction in glutathione (GSH) and an increase in zinc protoporphyrin
      (ZPP) suggesting an altered haem synthesis pathway. Only DMSA was able to
      increase the activity of ALAD, while both taurine and DMSA were able to
      significantly increase GSH level towards normal. Animals treated with taurine
      significantly reduced the alterations in some of the biochemical parameters
      indicative of oxidative stress. Thiobarbituric acid reactive substance (TBARS)
      levels reduced significantly in liver, kidney and red blood cells, while GSH
      level increased. Activity of superoxide dismutase (SOD) also showed an increase
      in blood and brain in animals treated with taurine. The data also provided a
      promising role of taurine during chelation of lead by potentiating the depletion
      of blood, liver and brain lead compared to DMSA alone. It can thus be concluded
      from the study that concomitant administration of an antioxidant could play a
      significant and important role in abating a number of toxic effects of lead when
      administered along with the thiol chelators.

PMID- 15171567
TI  - Oximes-induced reactivation of rat brain acetylcholinesterase inhibited by VX
      agent.
AB  - A comparison of one mono- and seven bisquaternary acetylcholinesterase (AChE)
      reactivators of acetylcholinesterase inhibited by VX agent was performed. As a
      source of the acetylcholinesterase, a rat brain homogenate was taken. There were
      significant differences in reactivation potency of all tested oximes. The oxime
      TO205 seems to be the most efficacious followed by TO046, HI-6, HS-6, K027,
      obidoxime, MMC and 2-PAM. In addition, the results of this study showed that the
      reactivation potency of the tested reactivators depends on many factors--such as
      the number of pyridinium rings, the number of oxime groups and their position, as
      well as the length and the shape of linkage bridge between two pyridinium rings.

PMID- 15171568
TI  - Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes
      decreased steady state mitochondrial DNA (mtDNA) and increased lactate
      production.
AB  - Haematopoietic suppression is one of the dose-limiting side effects of chronic
      zidovudine (AZT) therapy. We tested the hypothesis that AZT would reduce
      mitochondrial DNA (mtDNA) content in haematopoietic progenitors causing impaired
      haematopoiesis and mitochondrial dysfunction. We studied the effects of AZT 0-50
      microM in vitro, on normal human CD34+ haematopoietic progenitor cells cultured
      ex vivo for up to 12 days. The mean AZT IC50 for granulocyte (phenotype
      CD15+/CD14-) and erythroid (phenotype glycophorin+/CD45-) cell proliferation was
      2.5 microM (SD+/-0.7) and 0.023 microM (SD+/-0.005), respectively. In myeloid
      rich cell cultures, the mean lactate content of the media, compared to untreated
      controls, increased by 86% (SD+/-23) at 10 microM AZT and in erythroid-rich
      cultures it increased by 134% (SD+/-24) in the presence of 0.5 microM AZT. In
      myeloid-rich cultures the AZT IC50 for the reduction in the mitochondrial/nuclear
      DNA content ratio was 5.6 microM, whereas in erythroid rich cultures this AZT
      IC50 was < 0.0005 microM. AZT produced concentration-dependent inhibition of
      CD34+ progenitor proliferation into both myeloid and erythroid lineages;
      erythropoiesis was more sensitive than myelopoiesis. Concurrently, AZT reduced
      steady state mtDNA content, while increasing lactate production. These findings
      support the hypothesis that mtDNA is one of the intracellular targets involved in
      the pathogenesis of AZT-associated bone marrow progenitor cell toxicity.

PMID- 15171569
TI  - Sodium nitroprusside impairs sexual competence of male rats.
AB  - Recently, sodium nitroprusside (SNP), a potent nitric oxide (NO) donor and a
      clinically used antihypertensive, has been introduced as a penile self-injection
      medical therapy for erectile dysfunction. However, it is known that many
      antihypertensives impairs sexual competence; NO regulates sexual competence and
      NO is cytostatic and cytotoxic for human sperm. Thus, a possibility exists that
      SNP may impair male reproductive competence. Testing this aspect is the aim of
      this study. This was assessed in male rats (using three i.p. doses: 60, 30 or 20
      microg/kg) using noncompetitive copulation tests. The results show that the
      highest dose of SNP was toxic and caused rapid mortality of treated rats (within
      30 min). The mid and low doses of SNP reversibly impaired several parameters of
      sexual competence in a dose-related fashion: sexual arousability, libido and
      sexual vigour. Some parameters of sexual behaviour remained unaltered: sexual
      motivation and intromission ratio, whilst one parameter was improved: sexual
      performance. In complete contrast, the ejaculatory competence and fertility
      remained unchanged. The SNP-induced impairments in sexual competence may be
      attributable to lowered testosterone levels and sedation mediated via its
      specific action and/or side effect. Further, this impairment of sexual function
      was not due to general toxicity, inhibition of penile sensitivity, penile
      erection or analgesic activity. It is concluded that SNP impairs male sexual
      competence, at least, in rats although it promotes penile erection.

PMID- 15171570
TI  - Systemic absorption of lithium following ingestion of a lithium button battery.
AB  - Accidental ingestion of electrical batteries occurs commonly in children. This
      rarely is associated with severe morbidity and mortality. Significant symptoms
      can arise due to leakage of alkali or heavy metals from the battery after
      degradation in the gastrointestinal tract. The main heavy metal of concern in
      electrical batteries is mercury; this is the first report of ingestion of a
      lithium battery in a child associated with systemic absorption of lithium.

PMID- 15171571
TI  - Reliability of the Glasgow Coma Scale for the emergency department evaluation of
      poisoned patients.
AB  - The Glasgow Coma Scale (GCS) was developed for monitoring the mental status of
      head-injured patients in the intensive care unit. The purpose of this study is to
      determine the inter-rater reliability of the GCS for poisoning patients in the
      emergency department. METHODS: This was a prospective, observational study. Two
      observers used a standard assessment checklist to determine the GCS of suspected
      poisoning patients. Inter-rater reliability was assessed with a weighted Kappa
      score. RESULTS: A total of 39 patients were enrolled. Weighted kappa for the
      total GCS demonstrated excellent agreement. Agreement was also good for each
      component of the score. CONCLUSION: The GCS is a reliable tool for the evaluation
      of mental status of poisoning patients in the emergency department.

PMID- 15171572
TI  - The relationship between prosthetics and orthotics services and community-based
      rehabilitation. A joint ISPO/WHO statement revised December 2003.

PMID- 15171573
TI  - From major amputation to prosthetic outcome: a prospective study of 190 patients
      in a defined population.
AB  - In this prospective study, the overall treatment and outcome of patients that
      underwent major lower limb amputation in a defined population is described. The
      study was performed over a five year period in the Health Care District of North
      East Skane, Sweden. Some 190 patients, permanent inhabitants of the Health Care
      District, underwent major lower limb amputation. Sixteen (16) of these patients
      had amputations before the study started and went through late second leg
      amputation during the period. One hundred and seventy four (174) patients had
      primary major amputation. Seventy nine (79) were men and 95 were women, with a
      median age of 81. The re-amputation rate was 17% although the primary knee
      preservation ratio was as high as 3.0:1. Rigid dressing was the standard method
      following trans-tibial amputation and was used for 5-7 days. ICEROSS silicone
      liner was used for compression therapy in 90% of all cases that resulted in
      delivery of a prosthesis. Prostheses were delivered to 43% of all patients with
      primary amputations. These patients spent a median of 13 days at the orthopaedic
      clinic. 55 days at the rehabilitation unit. Pressure casting was used as a
      standard method in the production of the prosthetic socket. ICEX carbon-fibre
      socket was used in 52%. New procedures, treatments and techniques were
      introduced, standardised and evaluated whilst the routines in the hospital were
      reorganised. In this way, a system has been implemented that better guarantees
      the outcome of the whole procedure and the service received by this category of
      patients.

PMID- 15171574
TI  - A randomised trial of rigid stump dressing following trans-tibial amputation for
      peripheral arterial insufficiency.
AB  - BACKGROUND: A multicentre randomised controlled trial to determine the effect of
      a rigid plaster dressing applied at the time of trans-tibial amputation on the
      number of days to casting for a prosthesis, and the incidence of post-operative
      stump infection. METHODS: Patients requiring trans-tibial amputation were
      randomised to one of 2 groups: In Group 1 (intervention) a rigid above-knee
      plaster dressing was applied at operation and patients were managed according to
      a standard protocol. Group 2 (control) had the individual surgeons' usual non
      rigid dressing regime. Rehabilitation data were extracted from the national
      physiotherapy database. On completion of the trial a questionnaire was sent to
      all participants. RESULTS: 14 surgeons in 7 centres enrolled 154 patients, with
      96 ultimately cast for a prosthesis. Patients who received a rigid dressing (n =
      78) had reduced days to casting (median 36, confidence interval 30-47) when
      compared with other dressings (n = 76) (median 42, confidence interval 36-45),
      these differences did not reach statistical significance. There was no
      significant difference in post-operative infection rates in the two groups. 64%
      of surgeons, and all physiotherapists and vascular nurses responding to the post
      trial questionnaire felt that the rigid dressing was an improvement on their
      normal regime and wished to continue with the technique. CONCLUSIONS: Despite a
      median reduction of 6 days in time to casting in patients treated with a rigid
      post-operative dressing this failed to reach statistical significance. The
      majority of participants who replied to the post-trial questionnaire expressed a
      wish to continue using the rigid dressing technique. To confirm that the trends
      shown in this trial are statistically valid a larger trial is needed.

PMID- 15171575
TI  - Effect on gait and socket comfort in unilateral trans-tibial amputees after
      exchange to a polyurethane concept.
AB  - Trans-tibial amputees with different indications for amputation often have stump
      problems. Many active amputees have limits in daily life and sports activities
      because of pressure ulcers, friction, allergic dermatitis or volume changes. Many
      methods and materials have been tried to make a well-fitted socket. A new
      polyurethane concept had been designed with a shock absorbing effect. The purpose
      of this prospective study was to compare a conventional suspension with a
      polyurethane concept with regard to the amputees' satisfaction, socket comfort,
      physical capacity and to analyse the long-term effect. The total material
      includes 29 unilateral trans-tibial amputees. They answered a questionnaire after
      2 months use of the polyurethane concept and were interviewed after 3 and 5
      years. After 3 years 22 amputees and after 5 years 20 amputees used the
      polyurethane concept. Gait was registered in 7 amputees. Speed and symmetry index
      (SI) for temporal, stride and kinematics variables were used to evaluate gait.
      The amputees reported that the polyurethane concept was better or much better in
      physical capacity in 117 (67%) and socket comfort was better or much better in
      119 (82%) compared with the conventional suspension. There was no obvious
      symmetry difference in gait variables in speed, step length, step time or single
      support or in kinematics knee variables. The amputees tended to walk faster,
      decrease in symmetry in temporal and stride variables and increase in symmetry in
      kinematics variables with the polyurethane concept. After 5 years 6 had died and
      20 amputees of the surviving 23 used the polyurethane concept. CONCLUSIONS: The
      polyurethane concept increased comfort considerably and physical activity
      increased when the trans-tibial amputees changed from conventional suspension.
      Gait registration was not useful to evaluate the amputees' satisfaction or socket
      comfort.

PMID- 15171576
TI  - Lower limb landmine injuries.
AB  - The medical records of 186 patients seeking treatment for landmine injuries in
      the authors' region between 1993 and 2001 were evaluated. Of these patients 13
      died of accompanying complications. Ten (10) patients with general body trauma
      and upper limb trauma were excluded from the study. Of 163 patients with lower
      limb injuries included in the study, 21 with traumatic amputation underwent
      surgical amputation at different levels. Patients without traumatic amputation
      were divided into 2 groups. There were 41 patients (29%) in Group I who were
      treated by limb salvage procedures. Treatments used in Group I including wound
      debridement, tendon repair, skin approximation, minimal osteosynthesis, external
      fixation of long bones and secondary wound coverage. In Group II, there were 101
      patients (71%) with primary amputation. Trans-tibial amputation was performed in
      52 cases (51.4%), ankle disarticulation in 24 (23.7%), trans-femoral amputation
      in 9 (8.9%), partial foot amputation in 8 (7.9%), knee disarticulation in 7
      (6.9%) and hip disarticulation in 1 case. In Group I, there was infection in 21
      patients (51.2%), revision in 27 (65.8%), and amputation in 15 (36.5%). In Group
      II, there was infection in 28 patients (27.7%), revision in 17 (16.8%), and
      amputation at a higher level in 8 (7%). In crush injuries such as those resulting
      from landmines, soft tissue, vascular, and neurological assessment must be
      performed with utmost care. Even so, the desired success in interventions
      intended to save a limb is complicated by a high infection rate, soft tissue
      complications, and high revision amputation rates. Therefore, a decision to
      amputate in the early term based on an accurate preoperative assessment is
      crucial.

PMID- 15171577
TI  - A new structural concept in moulded fixed ankle foot orthoses and comparison of
      the bending stiffness of four constructions.
AB  - There are many reasons why a rigid ankle foot orthosis (AFO) may be prescribed.
      In some cases it is desirable that the rigidity is sufficient to maintain a
      constant ankle position throughout the gait cycle. There is a need to determine a
      design of cosmetic, lightweight AFO that provides the necessary stiffness whilst
      being acceptable to the patient, encouraging continued wear with the resultant
      benefits. This paper describes an investigation of AFO resistance to
      dorsiflexion, comparing the stiffness of an AFO with forward trim lines, two
      designs of reinforced AFOs and an AFO with forward trim lines and an external
      ankle strap. One reinforced AFO had corrugations moulded in the polypropylene
      around the ankle, the other had carbon fibre inserts attached to the inside of
      the polypropylene. The emphasis was on testing the mechanical stiffness of the
      four AFO designs: the test procedure did not mimic the patterns of AFO loading
      during gait. Each design was tested in the same manner by the same examiner. The
      AFO with forward trimlines and an ankle strap displayed similar stiffness to the
      carbon fibre reinforced AFO and both were stiffer than the other two designs.

PMID- 15171578
TI  - Correlation between quantity and quality of orthosis wear and treatment outcomes
      in adolescent idiopathic scoliosis.
AB  - Orthotic treatment is the most commonly used non-surgical treatment method for
      adolescent idiopathic scoliosis (AIS). This study determined whether treatment
      outcome correlates with how often and how well children with AIS wear their
      orthoses. Eighteen (18) subjects (3M, 15F) who were diagnosed with idiopathic
      scoliosis and had worn their orthoses from 6 months up to 1 year participated in
      this study. All subjects were prescribed Boston braces to be worn full time (23
      hrs/day). Twelve (12) subjects who completed their brace treatment were included
      in the data analysis. Three (3) treatment outcomes were classified as
      improvement, no change and deterioration. The quality of the brace wear was
      assessed by how often the brace was worn with zero force, below 80%, between 80
      to 120%, and above 120% of the load level prescribed in the clinic. The quantity
      of brace wear was determined by how many hours per day they wore their brace.
      Subjects who wear their braces tighter and for more hours per day seem to have
      better outcomes.

PMID- 15171579
TI  - Enhancement of prosthetics and orthotics learning and teaching through e-Learning
      technology and methodology.
AB  - A Write-Once Publish-Everywhere model was used to create and deliver on-line
      clinical training and education for undergraduate prosthetics and orthotics
      students. This project consisted of three phases: developing multimedia learning
      and teaching tools, integrating these tools into the curriculum (combination of e
      Learning and live practical sessions), and evaluating the outcomes. Video-based
      multimedia contents were captured and integrated with graphic, audio and text
      into a PowerPoint presentation software format. The web-based content was
      integrated into the WebCT platform for course management. Questionnaires were
      used to obtain student feedback on this e-Learning approach. Results were
      compared within the prosthetics and orthotics (P&O) programme, with other Health
      Sciences programmes, and overall with the University. P&O student responses were
      significantly higher than other groups for career relevance and problem solving.
      Qualitative feedback indicated that students appreciated the easy access,
      integrated and interactive approach of the text materials, concise PowerPoint
      presentation, demonstration video and the on-line case discussion via the WebCT
      platform. Educators appreciated the ability easily to maintain contents and
      publish the modules across multiple media without recreating the contents.

PMID- 15171580
TI  - Custom skiing and trekking adaptations for a trans-tibial and trans-radial
      quadrilateral amputee.
AB  - A keen skier who is a trans-tibial and trans-radial quadrilateral amputee sought
      an improved adaptation for skiing from the Rehabilitation Engineering Service in
      Edinburgh. The unpredictable nature of the bending moments and loads that can be
      imposed on the prostheses during skiing raised concern about the suitability of
      standard prosthetic components for this purpose. The authors report a ski boot
      modification that incorporates mechanical protection for the standard prosthetic
      components and a description of the custom-adapted alpine trekking sticks used
      also as ski poles. Reference is made to the role of risk assessment, the design
      and manufacture in providing this type of custom-made rehabilitation device.

PMID- 15171582
TI  - A new walking orthosis for paraplegics: hip and ankle linkage system.
AB  - For paraplegics, two major disadvantages of hip-knee-ankle-foot orthotic systems
      that have a medial single hip joint are the short stride and horizontal rotation
      of the pelvis. The authors consider the pelvic rotation is caused by two factors;
      one is the lack of a mechanism to assist hip flexion, and the other is fixed
      ankle joints that cause instability when the step length becomes longer. Users
      must rotate their pelvis to initiate a swing in their legs and to achieve
      stability by making their two legs as parallel as possible in order to avoid
      losing balance. To overcome those disadvantages, the authors developed a new
      orthosis named "HALO" (Hip and Ankle Linked Orthosis), which has a linking
      mechanism that connects both ankle joints with a medial single hip joint. This
      new orthosis allows users to keep both feet always parallel to the floor while
      walking, and assists the swinging of the leg when the contralateral ankle is
      flexed dorsally by loading. Gait analysis revealed that the pelvic rotation with
      "HALO" either in parallel bars or with Lofstrand crutches was within 20 degrees,
      which was within the physiologically normal level.

PMID- 15171581
TI  - An automatic hinge system for leg orthoses.
AB  - This paper describes a new automatic hinge system for leg orthoses, which
      provides knee stability in stance, and allows knee-flexion during swing.
      Indications for the hinge system are a paresis or paralysis of the quadriceps
      muscles. Instrumented gait analysis was performed in three patients, fitted with
      this new hinge system in a knee orthosis. The orthosis proves to satisfy the
      patients allowing them to walk without a knee-lock system.

PMID- 15171583
TI  - Comparison of rocking edge spacing for two common designs of swivel walkers.
AB  - Two commonly used designs of swivel walker are the Consort 800 and the ORLAU
      1000. This paper examines how the footplate rocking edge spacing varies between
      these two designs and then considers how lateral stability might be influenced if
      reduced separation is introduced to facilitate ambulation for less able users. In
      general it is shown that there should be no obstacles to such variation on the
      part of an orthotist thereby improving access to these devices and function for
      disabled individuals.

PMID- 15171584
TI  - Neural prostheses and functional electrical stimulation.

PMID- 15171585
TI  - Neural prostheses in clinical applications--trends from precision mechanics
      towards biomedical microsystems in neurological rehabilitation.
AB  - Neural prostheses partially restore body functions by technical nerve excitation
      after trauma or neurological diseases. External devices and implants have been
      developed since the early 1960s for many applications. Several systems have
      reached nowadays clinical practice: Cochlea implants help the deaf to hear,
      micturition is induced by bladder stimulators in paralyzed persons and deep brain
      stimulation helps patients with Parkinson's disease to participate in daily life
      again. So far, clinical neural prostheses are fabricated with means of precision
      mechanics. Since microsystem technology opens the opportunity to design and
      develop complex systems with a high number of electrodes to interface with the
      nervous systems, the opportunity for selective stimulation and complex implant
      scenarios seems to be feasible in the near future. The potentials and limitations
      with regard to biomedical microdevices are introduced and discussed in this
      paper. Target specifications are derived from existing implants and are discussed
      on selected applications that has been investigated in experimental research: a
      micromachined implant to interface a nerve stump with a sieve electrode, cuff
      electrodes with integrated electronics, and an epiretinal vision prosthesis.

PMID- 15171586
TI  - Restoring hearing with active hearing implants.
AB  - Due to shortcomings of conventional hearing aid technology, such as
      unsatisfactory sound quality due to limited frequency range and undesired
      distortion, occlusion of the outer ear canal, and acoustic feedback with high
      amplification, but also psychological aspects of stigmatization, a significant of
      patients in need of hearing aids are actually not wearing them. Active hearing
      implants can be distinguished in: (1) impedance transformation implants (ITI),
      (2) cochlear amplifier implants (CAI), (3) cochlear implants (CI), and (4) brain
      stem implants (BSI). Whereas ITI are designed for patients with middle ear
      hearing loss, CAI are intended to restore hearing in patients with inner ear
      hearing loss. Advantages of CAI may be: (1) improved sound fidelity, (2) no
      occlusion of the outer ear canal, (3) no feedback, and (4) invisibility. However,
      not all features are true for every device. CI replace inner ear function in deaf
      or almost deaf patients. This article gives an overview on the range of active
      hearing implants to restore hearing and outlines the future use of computer and
      robot aided surgery.

PMID- 15171587
TI  - Neuroprosthetic hearing with auditory brainstem implants.
AB  - The auditory brainstem implant (ABI) does provide auditory sensations,
      recognition of environmental sounds and aid in spoken communication in about 300
      patients worldwide. It is no more an investigative device but widely accepted for
      the treatment of patients who have lost hearing due to bilateral tumors of the
      hearing nerve who transmits the acoustic information from the cochlea to the
      brain. Most of the implanted patients are completely deaf when the implant is
      switched off. In contrast to cochlear implants, only few of the implanted
      patients achieve open-set speech recognition without the help of visual cues. On
      average, the ABI improves communicative functions like speech recognition at
      about 30% when compared to lip-reading only. The task for the next years is to
      improve the outcome of ABI further by developing new less invasive operative
      approaches as well as new hardware and software for the ABI device.

PMID- 15171588
TI  - Deafferentation of the urinary bladder and implantation of a sacral anterior root
      stimulator (SARS) for treatment of the neurogenic bladder in paraplegic patients.
AB  - Since 25 years electrical stimulation has become an established and widely
      acknowledged therapy option. Today, FES is widely employed, e.g. for
      cardiostimulation, diaphragm stimulation, kinetotherapy, for treatment of tremor
      in Parkinson patients, and finally for bladder stimulation in patients with
      bladder voiding dysfunctions. Brindley was the first researcher who succeeded in
      stimulating the spinal nerves via implanted electrodes in an animal model. In the
      years 1978/79 Brindley implanted five paraplegic patients with so-called sacral
      anterior root stimulators; all of them were able to void under stimulation. This
      method of sacral anterior root stimulation (SARS) proved an alternative to
      frequent one-way catheterisation for patients with severe voiding dysfunctions,
      without achieving complete continence, however. The following study is to provide
      an overview over the latest insights in the context of implanting sacral anterior
      root stimulators; it discusses the preconditions required for such interventions
      and presents criteria to decide in which cases there is a contraindication for
      sacral deafferentation of the posterior roots. Moreover, it contrasts advantages
      and disadvantages of the intradural and extradural implantation methods and
      presents the currently available long-term follow-up results with SDAF and SARS
      for treatment of bladder voiding dysfunctions.

PMID- 15171589
TI  - Neuroprosthetics of the upper extremity--clinical application in spinal cord
      injury and future perspectives.
AB  - Within the last couple of years, partial restoration of lost motor functions in a
      larger number of spinal cord injured patients has become possible by the
      introduction of neuroprostheses into the clinical environment. The Freehand
      system in particular is the first implantable neuroprosthesis from which a
      certain group of tetraplegic patients with stable shoulder function, but missing
      or weak grasp and hold function of the hand do benefit. The system is based on
      the combination of electrical stimulation and operative tendon transfers and thus
      represents a multicomponent concept for long-term restoration of the grasp
      function. The crucial prerequisites for successful use of an implantable
      neuroprosthesis are the right indication, careful preoperative muscle
      stimulation, differentiated planning of the surgery and functional training
      adopted to the individual residual functions. After successful completion of an
      extensive rehabilitation program, patients are able to use the system for
      activities of daily living without the need for special additional aids, which
      enhances their quality of life and independency. In order to extend the group of
      potential users of neuroprostheses in the future, new technological developments
      will have to take into account that nowadays the majority of spinal cord injured
      patients suffer from an incomplete lesion of the spinal cord. For these
      particular patients who still possess residual functions, modular, "naturally"
      controllable systems for supporting these functions are needed rather than
      complex systems to substitute them.

PMID- 15171591
TI  - [A bottle is not just a bottle. Glass in pharmacy].

PMID- 15171590
TI  - The retina implant--new approach to a visual prosthesis.
AB  - Currently, no treatment is available for degenerative diseases of retinal
      photoreceptors. The patients are faced with a high risk of blindness. Biological
      approaches failed to prove efficacy. A new concept for the treatment of disorders
      like retinitis pigmentosa is electrical stimulation at various levels of the
      visual system. Therefore, devices were fabricated with stimulating electrodes
      contacting retinal or central neurons to elicit biological activity in these
      cells. It became possible to fabricate even complex devices with an external
      power supply encapsulated within biocompatible materials. Animal experiments
      showed that with implanted prototypes cortical activation could be achieved and
      first experiments in blind human subject also suggest that vision can be
      restored, however at present in a very low range of simply identifying spots of
      light. Further developments and also the continuation of animal experiments are
      necessary before the clinical application will become a standard procedure.

PMID- 15171593
TI  - [Cervical cancer: new methods of prevention].

PMID- 15171592
TI  - [Escitalopram: a chiral agent for treatment of depression].

PMID- 15171594
TI  - [Drug therapy in and childhood and old age].

PMID- 15171595
TI  - [Weight increase after smoking cessation--fate or lack of self-discipline?].

PMID- 15171596
TI  - [Influences on fermentation and thiamine metabolism in bovine rumen fluid (in
      vitro)--part 3: Effects of artificially contaminated hay with Cladosporium
      herbarum and Fusarium graminearum, respectively].
AB  - The influence of contaminated hay [Cladosporium herbarum (CL) and Fusarium
      graminearum (FU), respectively] on fermentation and thiamine metabolism of bovine
      rumen content was investigated using the longterm rumen simulation technique
      (RUSITEC). Six investigation periods 25 days long each were carried out. A nine
      days feeding period with normal hay was followed by the testphase I (five days)
      with a mixture of normal and mouldy hay and testphase II (five days) with
      additive an 0.3 mg thiamine per reaction vessel. The last four days served as
      regeneration time with normal hay. The following marginal effects of mouldy hay
      on rumen fermentation patterns could be noted. A) During testphase I: cellulase
      activity: +10.0% (FU); alternation of the thiamine derivate pattern, but no
      effect on total thiamine content (CL, FU). B) During testphase II the results
      were more obvious: bacterial protein synthesis: -22.6% (CL), -24.4% (FU).
      Alternation of the fatty acid pattern: propionate (-7.30% FU), n-butyrate (-3.90%
      CL, +3.49% FU), n-valerate (-8.5% CH, FU). Cellulase activity: -17.0% (CL, FU).
      But no effect on total thiamine (CL, FU); alternation of the thiamine derivate
      pattern: more non phosphorylate thiamine. The noted effects on rumen fermentation
      and thiamine metabolism were not severe enough to be responsible for the
      development of a CCN.

PMID- 15171597
TI  - [Synchronization of ovulation (OVSYNCH) in high producing dairy cattle herds.
      Part II: Milk yield, diseases and cost-benefit-analysis].
AB  - A method for synchronization of ovulation (OVSYNCH) was evaluated for its
      practical use in seven North German dairy cattle herds. The original procedure of
      PURSLEY et al. (1995) was applied, i. e. cows were treated with Gonadotropin
      Releasing Hormone (GnRH) at a random stage of the estrous cycle, followed by an
      injection of a prostaglandin F2alpha (PGF2alpha)-analog seven days later and
      another injection of GnRH two days after PGF2alpha. Cows were inseminated 24 h
      after the last injection by artificial insemination. Control animals were
      assigned by corresponding lactation number and month of lactation. Cows from the
      OVSYNCH group returned to the conventional reproductive management after the
      OVSYNCH treatment, which was the same management as that for the control group.
      The parameters of fertility and correlations between body condition score (BCS)
      as well as concentrations of serum progesterone and the success of OVSYNCH were
      presented in the first report. For the OVSYNCH group, the 100-day-duction during
      the time period from calving until a pregnancy was established differed markedly
      from healthy cows in a variety of parameters. Healthy cows had a greater FSC
      (65.22%) than sick cows (35.90%) (P < 0.05). Furthermore, mean days open were
      less in healthy cows than in sick cows (85.48 +/- 30.56 days vs 110.85 +/- 46.40
      days) (P < 0.05). Cows showing a disease had a higher number of lactation (4.00
      +/- 2.26 vs. 2.80 +/- 1.35; P < 0.01) and a decreased BCS (2.72 +/- 0.23 vs. 2.91
      +/- 0.23; P < 0.05). Sick and healthy cows from the OVSYNCH group did not differ
      with regard to 100-day-milk-yield (milk kg, relative and absolute milk fat and
      protein content). The cost-benefit-analysis revealed higher total cost, and cost
      per pregnancy (16,408.07 euros and 278.10 euros, respectively) in the control
      group than in the OVSYNCH group (11,015.69 euros and 196.71 euros, respectively).

PMID- 15171598
TI  - [Concentrations of L-carnitine and parameters of lipid metabolism during estrus
      in broodmares].
AB  - In the present study the concentrations of L-carnitine (total carnitine, free
      carnitine, and acyl carnitine) and several parameters of the lipid metabolism
      were measured during the estrus in 10 broodmares. The carnitine concentrations
      varied in a wide range between the mares. The differences of the mean carnitine
      concentrations during the estrus did not reach the level of significance (P <
      0.05). There was no relationship between the concentrations of total and free
      carnitine to the follicle size; however, the concentration of acyl carnitine was
      significantly correlated (r = -0.42). Because of the individual variations of
      carnitine concentrations, the non-significant differences of carnitine
      concentrations between the estrus days, and the weak relationship between the
      carnitine concentrations and the follicle size, it seems impossible to estimate
      the time of ovulation based on the carnitine concentration, as it was suggested
      in a previous study. The parameters of lipid metabolism did not show any
      significant changes during the estrus period.

PMID- 15171599
TI  - [Brachyury in German Holstein cattle].
AB  - In 11 German Holstein cattle with black and white or red and white coat colour
      short tails could be observed. All affected animals were born in different farms.
      A clinical examination could not reveal further congenital anomalies of other
      organs. The parents of the affected animals showed no abnormalities of the tail.
      The pedigree data showed that all short tailed animals were related with each
      other and this fact provides evidence that brachyury is an inherited congenital
      anomaly. The coefficients of relationships were between 0.20 and 25%. The
      pedigree indicated a monogenic or oligogenic autosomal recessive inheritance.
      Environmental factors causing short tails in these animals were not obvious.

PMID- 15171600
TI  - [Diprosopus in calves of different breeds].
AB  - Three calves of the breeds German Holstein, German Angus and German Fleckvieh
      from three farms were born showing different forms of facial duplication. Two
      calves were classified as diprosopus with tetraophthalmus and in one calf a
      partial duplication of the forehead with a third nostril was observed. Further
      relatives of these affected calves or animals in the same herds were not affected
      by diprosopus. The calves with diprosopus were examined by means of clinical and
      pathological-anatomical methods. The increased occurrence of twin births and
      inbreeding could be of importance for the observed congenital anomaly, whereas
      conception early in life and conception during the winter months of the mothers
      of the affected calves are unlikely as reasons for the observed congenital
      anomaly of these calves. Even if the cases of diprosopus showed no increased
      frequency by paternal half sib groups, it is likely that diprosopus is
      genetically influenced and a larger number of genes may determine the phenotype.

PMID- 15171601
TI  - Seasonal changes in reproductive parameters and seminal plasma constituents of
      rams in Afyon province of Turkey.
AB  - The objective of the present study was to describe seasonal changes in semen
      quality, serum testosterone and seminal plasma constituents for 9 months in 10
      rams from a mature local (Daglic) and imported breed (Chios) under Afyon province
      conditions typical for the internal Anatolian region. Sperm motility and sperm
      concentration and testosterone level were higher, percentage of abnormal
      spermatozoa was the lowest during autumn. The biochemical analyses of ram seminal
      plasma indicated that the highest values of total protein, albumin (A), globulin
      (G), total lipid and cholesterol were recorded in autumn while A/G ratio
      exhibited the lowest values. Aspartate amino transferase (AST) activity and
      AST/ALT ratio recorded the lowest values, while moderate values were recorded for
      alanine amino transferase (ALT) activity in autumn. The results suggest that the
      rams under Afyon province conditions show seasonal changes for some reproductive
      parameters and seminal plasma constituents.

PMID- 15171602
TI  - Pharmacokinetics and tissue residue profiles of erythromycin in broiler chickens
      after different routes of administration.
AB  - This study investigated the disposition kinetics and plasma availability of
      erythromycin in broiler chickens after single intravenous (i.v.), intramuscular
      (i.m.), subcutaneous (s.c.) and oral administrations (p.o.) of 30 mg kg(-1) b.
      wt. Tissue residue profiles were also studied after multiple intramuscular,
      subcutaneous, and oral administration of 30 mg kg(-1) b. wt., twice daily for
      three consecutive days. Plasma and tissue concentrations of erythromycin were
      determined using microbiological assay methods with Micrococcus luteus as the
      test organism. Following intravenous injection, plasma concentration-vs-time
      curves were best described by a two compartment open model. The decline in plasma
      drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.19 h and
      (t(1/2beta)) 5.3 h for distribution and elimination phases, respectively. After
      intramuscular, subcutaneous and oral administration erythromycin at the same dose
      was detected in plasma at 10 min and reached its minimum level 8 h post
      administration. The peak plasma concentration (Cmax) were 5.0, 5.3, and 6.9
      microg x ml(-1) and were attained at 1.7, 1.4, and 1.3 h (Tmax), respectively.
      The elimination half-lives (T(1/2el)) were 3.9, 2.6, and 4.1 h and the mean
      residence times (MRT) were 3.5, 3.2, and 3.6 h, respectively. The systemic
      bioavailabilities were 92.5, 68.8, and 109.3%, respectively. In vitro protein
      binding percent of erythromycin in broiler plasma was ranged from 21 to 31%. The
      limit of quantification (LOQ) for the assay was 0.03 microg x ml(-1) in plasma
      and tissues. The tissue level concentrations were highest in the liver, and
      decreased in the following order: plasma > kidney > lung > muscle and heart. No
      erythromycin residues were detected in tissues and plasma after 24 h except in
      liver and kidney where it persisted during 48 h following intramuscular and oral
      administrations.

PMID- 15171603
TI  - The influence of prepartal bacteriuria on the reproductive performance of the
      sow.
AB  - In a Slowakian indoor pig production unit, with high prevalence of vaginal-vulval
      discharges, the sows were subjected one day prefarrowing to urine analysis. Sows
      suffering urinary tract infection (UTI) were assigned to an UTI group (group 1, n
      = 384), the remaining sows were classified as free of UTI and were assigned to
      group 2 (n = 1099). Total born litter size, liveborn litter size, weaning litter
      size and the occurrence of periparturient diseases, reasons for sow cullings at
      weaning, subsequent weaning to estrus intervals, conceptions- and farrowing rate,
      next total born- and lifeborn litter size and the occurrence of periparturient
      diseases were evaluated. UTI having sows had smaller (p < 0.05) total born litter
      size (11.71 +/- 1.11) when compared to the healthy animals (12.97 +/- 1.25).
      Liveborn litter size was significantly (p < 0.01) lower in group 1 (10.21 +/-
      0.81 vs. group 2: 11.31 +/- 1.21). The occurrence of periparturient diseases
      revealed highly significant (p < 0.001) differences between the groups (group one
      26.24% vs. group two 4.64%). Weaning litter size showed significant (p < 0.05)
      differences between group 1 (9.21 +/- 1.02) and 2 (10.11 +/- 0.37). More (p <
      0.05) sows were culled post-weaning in the UTI group, compared to the healthy
      animals. Causes of post-weaning cullings differed between the groups: all sows of
      the group one had the pathological signs of swine urogenital disease at culling,
      while the majority of sows of the group 2 were culled due to locomotor problems
      and chronic mastitis. Subsequent weaning to estrus intervals, conceptions-, and
      farrowing rate and next total born litter size differed significantly (p < 0.05)
      between the groups, next lifeborn litter size (p < 0.01) and the occurrence of
      periparturient diseases (p < 0.001) were high significantly better in the healthy
      than in the UTI suffering group of sows. IMPLICATIONS: antepartal UTI might be
      the sign of swine urogenital disease and might negatively influence the sows
      reproductive performance.

PMID- 15171604
TI  - Cell death suppressors encoded by cytomegalovirus.

PMID- 15171605
TI  - Apoptosis regulator genes encoded by poxviruses.

PMID- 15171606
TI  - T-cell-mediated control of poxvirus infection in mice.

PMID- 15171607
TI  - Switching on and off the cell death cascade: African swine fever virus apoptosis
      regulation.

PMID- 15171608
TI  - Neuronal apoptosis pathways in Sindbis virus encephalitis.
AB  - Sindbis virus infects neurons of the brain and spinal cord leading to neuronal
      apoptosis and encephalitis in mice. During postnatal development, neurons of mice
      remain susceptible to infection but become refractory to SV-induced programmed
      cell death. Failure to undergo programmed cell death results in a persistent
      infection. However, some neurovirulent strains of Sindbis virus overcome the age
      dependent protective function in neurons, leading to enhanced apoptotic cell
      death in the central nervous system and higher mortality rates. Sindbis virus
      infections can also cause hind-limb paralysis due to the death of infected spinal
      cord motor neurons. However, spinal cord neuron death in older mice appears to
      occur by mechanisms that differ from classical apoptosis observed in newborn mice
      based on the morphology of dying neurons at these two sites. Sindbis virus
      infections of mosquitoes and some mosquito cell lines, on the other hand, do not
      induce cell death but persistent infections, a phenomenon also observed
      occasionally in cultured mammalian cells as well as in brains of infected mice
      surviving lethal infections. Thus, both viral and cellular factors contribute to
      the varied outcomes of infection. The molecular mechanisms that govern the
      susceptibility or resistance of particular cell types to SV-induced cell death
      are not well understood. Furthermore, the cellular execution machinery that
      produces the characteristic morphological distinctions between brain and spinal
      cord (i.e. apoptotic versus non-apoptotic) remain to be discovered.

PMID- 15171609
TI  - Apoptotic pathways triggered by HIV and consequences on T cell homeostasis and
      HIV-specific immunity.

PMID- 15171610
TI  - HIV and apoptosis: a complex interaction between cell death and virus survival.

PMID- 15171611
TI  - Poliovirus and apoptosis.

PMID- 15171612
TI  - Flaviviruses and apoptosis regulation.

PMID- 15171613
TI  - Manipulation of apoptosis by herpes viruses (Kaposi's sarcoma pathogenesis).

PMID- 15171614
TI  - Exploitation of cell cycle and cell death controls by adenoviruses: the road to a
      productive infection.

PMID- 15171616
TI  - Epstein-Barr virus signal transduction and B-lymphocyte growth transformation.
AB  - Latent EBV growth transformation of resting B-cells into indefinitely
      proliferating cell lines is a successful viral strategy for survival in its host
      and the basis of several human malignancies. EBV transforms cell growth through
      viral proteins that modify cell gene expression at the level of transcription or
      by appropriating signaling pathways. Analyses of the EBV-transforming protein
      LMP1 have begun to reveal that this receptor transduces critical signals by
      appropriating the TNF receptor signal transduction pathway to activate NF-kappaB
      and MAPK. While this has brought an important aspect into clearer focus, future
      progress in delineating the underlying mechanism of transformation, which will be
      essential to devising effective therapies to treat EBV-associated malignancies,
      will depend on resolving the intricacies of TRAF signal transduction. Since
      expression of cytokines, receptors, and anti-apoptotic proteins are regulated by
      TRAF signaling, another critical issue is delineating the genes that are
      specifically targeted by LMP1 in order to transform B-lymphocyte growth.

PMID- 15171615
TI  - Induction of transformed cell-specific apoptosis by the adenovirus E4orf4
      protein.

PMID- 15171618
TI  - Signal transduction and apoptosis pathways as therapeutic targets.

PMID- 15171617
TI  - SV40 and Notch-I: multi-functionality meets pleiotropy.

PMID- 15171619
TI  - Quantitation and kinetics of CD51 surface receptor expression: implications for
      targeted delivery.
AB  - The CD51 integrin subunit is important in many functions ranging from mediation
      of adenovirus attachment and internalization to facilitation of angiogenesis.
      CD51 has also gained interest as an attractive ligand for directed therapy
      studies, including those for targeted gene delivery. While the function and
      importance of several CD51-specific targeting molecules have been examined,
      studies are often carried out without quantitative assessment of the receptor. A
      lack of this data complicates further mathematical analysis of targeting data and
      elucidation of the mechanism(s) underlying specific targeting. We performed a
      quantitative evaluation of CD51 receptors on the surface of HeLa cells, a common
      cell line utilized in many receptor-based studies, and compared them to other
      similar and dissimilar cell types. Unstimulated HeLa cells strongly express the
      CD51 receptor at a level of 212,700 +/- 12,000 (mean +/- SD) antibody binding
      capacity (ABC) cell(-1) (n = 3). Following irradiation with 3 Gy, receptor
      expression increases dramatically, peaking at a value of 403,700 +/- 26,400 (n =
      4). The utility of this quantitative information is highlighted by the
      application of our data to targeting studies from the literature. Taken together,
      the results yield more detailed information than is available with experimental
      targeting data alone.

PMID- 15171620
TI  - A reaction-diffusion model of basic fibroblast growth factor interactions with
      cell surface receptors.
AB  - Basic fibroblast growth factor (FGF-2) is a potent angiogenic growth factor
      involved in the development of diseases such as cancer, atherosclerosis, and
      heart and limb ischemia, as well as normal wound healing and tissue development.
      Despite being one of the most heavily studied angiogenic growth factors, the
      binding kinetics and signaling pathways of FGF-2 are still incompletely
      understood. In this study, we address the role of the low-affinity heparan
      sulfate proteoglycans (HSPGs), the identity of the minimal signaling complex
      leading to FGF-2 activity, and the importance of FGF-2 dimerization using a
      mathematical model of FGF-2 diffusion and ligand-receptor binding. Unique model
      features include the degradation of internalized cell surface species, the
      binding of a second FGF-2 ligand to a high-affinity FGF receptor (FGFR), and the
      dimerization of FGF-2 ligands. All experimentally determined reaction rates and
      diffusivity values are scaled to 37 degrees C. Our model results suggest that FGF
      2-induced cellular response is the result of a temporal combination of triads
      (FGF-2/HSPG/FGFR complexes), double triads (2 FGF-2/HSPG/FGFR complexes), and FGF
      2-bound HSPGs (FGF-2/HSPG complexes). Moreover, ligand dimerization is shown to
      potentially regulate FGF-2 activity by shifting the distribution of signaling
      complexes from the less stable triads to the more stable double triads.

PMID- 15171622
TI  - Non-episode-dependent assessment of paroxysmal atrial fibrillation through
      measurement of RR interval dynamics and atrial premature contractions.
AB  - A method is presented for classifying a single lead surface electrocardiogram
      recording from a Holter monitor as being from a subject with paroxysmal atrial
      fibrillation (PAF) or not. The technique is based on first assessing the
      likelihood of 30-min segments of electrocardiogram (ECG) being from a subject
      with PAF, and then combining these per-segment likelihoods to form a per-subject
      classification. The per-segment assessment is based on the output of a supervised
      linear discriminant classifier (LDC) which has been trained using known data from
      the Physionet Atrial Fibrillation Prediction Database (which consists of two
      hundred 30-min segments of Holter ECG, taken from 53 subjects with PAF, and 47
      without). One of two LDCs is used depending on whether there is a significant
      correlation between observed low-frequency and high-frequency spectral power in
      the RR power spectral density over the 30-min segment. If there is high
      correlation, then the LDC uses spectral features calculated over a 10-min window;
      in the low-correlation case, both spectral features and atrial premature
      contractions are used as features. The classifier was tested for its ability to
      distinguish PAF and non-PAF segments using three independent data sets
      (representing a total of 1370 segments from 50 subjects). The cumulative
      sensitivity, specificity, and accuracy on a per-segment basis were 43.0, 99.3,
      and 80.5%, respectively on these independent test sets. By combining the results
      of segment classification, a per-subject classification into PAF and non-PAF
      classes was performed. For the 50 subjects in the independent data sets, the
      sensitivity and specificity of the per-subject classifier were 100%.

PMID- 15171621
TI  - Peroxynitrite exposure of cells cocultured with macrophages.
AB  - Peroxynitrite is a potent oxidant that is formed endogenously from NO and O2-.
      One approach for studying its toxicity involves the coculture of activated
      macrophages (producers of NO and O2-) with "target cells" (which make O2- but not
      NO). Because peroxynitrite concentrations in such experiments are too small and
      localized to measure, reaction-diffusion models were developed for situations
      ranging from isolated cells to many cells randomly distributed on a plate. In
      these models the macrophage population created a constant NO concentration in and
      near all cells, whereas fluxes of O2- into the media from individual macrophages
      led to localized extracellular formation of peroxynitrite. Target cells were
      found to have no effect on the peroxynitrite concentrations in other cells,
      whereas the macrophage effects were additive. The average concentration inside
      randomly distributed target cells increased with increasing macrophage number
      density, as entry of extracellular peroxynitrite grew in importance relative to
      intracellular formation. For high cell densities, large peroxynitrite membrane
      permeabilities, and low rates of intracellular synthesis, the surrounding
      macrophages were calculated to double or triple the peroxynitrite concentration
      in an average target cell. It was estimated that a macrophage enveloping a target
      cell could cause as much as a 10-fold increase in the concentration inside that
      target cell.

PMID- 15171623
TI  - Contour definition and tracking in cardiac imaging through the integration of
      knowledge and image evidence.
AB  - The main contribution of this paper is the use of simple processing techniques,
      incorporated in a new multistage approach, to automatically delineate left
      ventricle contours. Another contribution is the proposal of the centerline
      distances for contour comparison, which promises a more accurate measurement than
      the common method, based on the distance to the closest point. Edges are detected
      by Gaussian filtering at coarse and fine scale. The region of interest is defined
      as a binary map where coarse edges are extracted throughout image sequence. A
      contour template is matched against the gradient of the first image. Candidate
      boundary points are instantiated by scanning the coarse edge map perpendicularly
      to the matched template. A candidate contour is estimated from these points by
      maximizing an edge likelihood function. A region growing algorithm gives another
      candidate contour. Both edge and region candidate contours are then integrated
      with the edge map computed at fine scale by maximizing another likelihood
      function. Evaluation was carried out on 12 echocardiographic and 4
      angiocardiographic sequences (for a total of 289 frames). Distances between
      computer-generated contours and the contours traced by three experts were within
      interobserver variability, unlike the results obtained by Acoustic Quantification
      and by a general-purpose deformable model.

PMID- 15171624
TI  - Sonorheometry: a noncontact method for the dynamic assessment of thrombosis.
AB  - Inappropriate blood coagulation plays a central role in the onset of myocardial
      infarction, stroke, pulmonary embolism, and other thrombotic disorders. The
      ability to screen for an increased propensity to clot could prevent the onset of
      such events by appropriately identifying those at risk and enabling prophylactic
      treatment. Similarly, the ability to characterize the mechanical properties of
      clots in vivo might improve patient outcomes by better informing treatment
      strategies. We have developed a technique called sonorheometry. Unlike existing
      methods, sonorheometry is able to assess mechanical properties of coagulation
      with minimal disturbance to the delicate structure of a forming thrombus.
      Sonorheometry uses acoustic radiation force to produce small, localized
      displacements within the sample. Time delay estimation is performed on returned
      ultrasound echoes to determine sample deformation. Mechanical modeling and
      parametric fitting to experimental data yield maps of mechanical properties.
      Sonorheometry is well suited to both in vitro and in vivo applications. A control
      experiment was performed to verify that sonorheometry provides mechanical
      characterization in agreement with that from a conventional rheometer. We also
      examined thrombosis in blood samples taken from four subjects. This data suggests
      that sonorheometry may offer a novel and valuable method for assessing the
      thrombogenicity of blood samples.

PMID- 15171625
TI  - Effect of boundary absorption in dispersion in Casson fluid flow in a tube.
AB  - The combined effect of yield stress and irreversible boundary reaction on
      dispersion process in a Casson fluid flowing in a conduit (pipe/channel) is
      studied using the generalized dispersion model proposed by Sankarasubramanian and
      Gill (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A
      333:115-132, 1973). The study describes the development of dispersive transport
      following the injection of a tracer in terms of the three effective transport
      coefficients, viz., exchange, convection, and dispersion coefficients. The
      exchange coefficient does not depend on yield stress but the convection and
      dispersion coefficients depend on yield stress or equivalently plug flow region.
      For large times, when the plug flow radius is one-tenth of pipe radius, the
      convective coefficient is reduced by 0.41 times of the corresponding value for a
      Newtonian fluid at equivalent wall absorption parameter; in channel case the
      reduction is by 39%. It is seen that the asymptotic dispersion coefficient
      decreases with increase in wall absorption parameter and yield stress of the
      fluid. When the plug radius in pipe (channel) is 0.1, depending upon the values
      of wall absorption parameter, say (0.01-100) the reduction factor in dispersion
      coefficient is in the range (0.1-0.3) in comparison to the values of the
      Newtonian case. The results reduce to those of Sankarasubramanian and Gill
      (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A 333:115
      132, 1973) when there is no yield stress for the pipe flow analysis and to those
      of Dash et al. (Dash, R. K., G. Jayaraman, and K. N. Mehta. Ann. Biomed. Eng.
      28:373-385, 2000) when there is no interphase mass transfer. The study can be
      used as a starting first approximation solution for studying the dispersion in
      the cardiovascular system.

PMID- 15171626
TI  - Cell orientation influences the biaxial mechanical properties of fibroblast
      populated collagen vessels.
AB  - Bioartificial tissues, composed of cells in a collagen matrix, can be fabricated
      with preferred cell orientations to mimic the histologic arrangement of biologic
      tissues. The influence of preferred cell orientations on the biaxial mechanical
      behavior of bioartificial tissues is unknown. Characterizing the biaxial
      mechanical behavior is necessary for better predicting the in vivo behavior of
      bioartificial tissues. Fibroblast populated collagen vessels (FPCVs) were
      fabricated with two different cell orientations by controlling the mechanical
      constraints during incubation. The cell orientation was verified by confocal
      microscopy and the collagen fiber organization was examined by confocal
      reflection and scanning electron microscopy (SEM). Pressure-diameter, force
      length tests were performed to determine the influence of cell orientation on the
      biaxial mechanical behavior. FPCVs were more extensible in the direction
      perpendicular to the preferred cell orientation, than in the direction parallel
      to the cell orientation. Biaxial tests were also performed in the presence of
      Cytochalasin D (Cyto D) to minimize the mechanical contribution of the cells.
      After Cyto D treatment, the FPCVs remained more extensible in the direction
      perpendicular to the cell orientation, even though a preferred collagen fiber
      orientation was not observed in the microscopy images.

PMID- 15171627
TI  - Stochastic and coherence resonance in an in silico neural model.
AB  - We show that it is possible for chaotic systems to display the main features of
      stochastic and coherence resonance. In particular, a model of coupled nonlinear
      oscillators which emulates the transmembrane voltage activities in CA3 neurons,
      operating in a chaotic regime and in the presence of noise, can exhibit coherence
      resonance and stochastic resonance. Certain firing frequencies become more
      "rhythmic" for some optimal values of noise intensity. The effect of noise in
      different coupling pathways is investigated. We found that the effect of
      coherence resonance and stochastic resonance are more prominent if noise is
      presented in either electric field or gap junction coupling pathways. Frequency
      sensitivity of the model is investigated as a preliminary step in illustrating
      the principles of possible epileptic seizure control strategies using "chaos
      control" concepts. Significant effects of stochastic resonance are observed in
      the 4-8 Hz range. Weaker effects can be found in the 1-4 Hz and 8-10 Hz ranges
      whereas 0.5 Hz does not exhibit any resonance phenomenon. Our results suggest
      that: (a) Stochastic resonance could enhance the intrinsic 4-8 Hz rhythms in CA3
      neurons more prominently via field coupling pathways. It could also help explain
      why some reported seizure control strategies using pulse-trains would only be
      effective at 0.5 Hz. (b) Stochastic resonance-like behavior can occur in the
      gamma range only if noise is presented via chemical synaptic pathways.

PMID- 15171629
TI  - Model predictions of the recruitment of lung units and the lung surface area
      volume relationship during inflation.
AB  - Experimental evidence suggests that the lung behaves as if it is composed of a
      large population of units which are recruited and derecruited during lung
      expansion and contraction. This study combines two previous models in order to
      estimate the probability distribution function describing lung unit opening
      pressures and the resulting alveolar surface area-volume relationship of the
      excised rat lung during inflation. Results indicate that the opening pressures of
      lung units during inflation can be described by a normal distribution. The end
      expiratory pressure (EEP) has a large effect on the number of lung units that
      open during inflation and the properties of the area-volume relationship of the
      lung, but the distribution of opening pressures of individual lung units is
      fairly consistent regardless of EEP. This study also presents evidence that when
      the normalized lung area-volume relationship is represented by the equation
      [A(L)]N = [phiV(L)]N(n) during inflation from the closed state, the expansion
      coefficient n is between 0.86 and 1. This result supports the theory that, for
      inflation from EEPs below 4 cmH2O, lung expansion occurs in part by the
      recruitment of lung units and not solely by the expansion of open units.

PMID- 15171628
TI  - Tension and stress calculations in a 3-D Fourier model of gall bladder geometry
      obtained from MR images.
AB  - Biliary tract obstruction results in dilatation of the biliary tract including
      the gall bladder and induction of symptoms such as abdominal pain. Since the pain
      receptors are likely mechano-sensitive receptors, it is important to develop
      tools for studying the distributions of tension and stress in the wall of the
      gall bladder. Wall tension and stress can be determined using Laplace's equation
      and the three-dimensional (3-D) geometry of a thin walled organ under equilibrium
      conditions. The objective of this study was to develop an analytical method to
      describe the 3-D geometry of the porcine gall bladder. The Fourier series method
      was used to describe the organ surface geometry obtained from magnetic resonance
      (MR) images. MR images of nine normal and three obstructed porcine gall bladders
      were analyzed. The curvature was computed throughout the gall bladder surface and
      the wall tension was computed using Laplace's equation. The spatial distributions
      of principal curvatures, tensions, and stresses were nonhomogeneous in the gall
      bladder because of its complex geometry. The extremum values of curvatures did
      not differ between normal and 2-day obstructed gall bladders. The pressure,
      tension, and stress were significantly higher, however, in the obstructed gall
      bladders (p < 0.05). This study provides an analytical tool for characterizing
      the complex 3-D geometry of an organ obtained from a clinical imaging modality.

PMID- 15171631
TI  - [Nursing--more than just a management factor].

PMID- 15171632
TI  - [International Day of Nursing May 12].

PMID- 15171630
TI  - An optimization algorithm for human joint angle time-history generation using
      external force data.
AB  - A mathematical model is presented that estimates joint kinematics and kinetics
      using measured external resultant loads and readily available parameters. The
      musculo-skeletal system was represented by a planar three degrees of freedom open
      kinematic chain. Information extraction was limited to the flexion-extension
      function of ankle, knee, and hip during quasi-planar motor tasks. Starting from
      plausible first approximation kinematics, other kinematic functions are
      iteratively generated by an optimization algorithm and corresponding ground
      reaction loads are calculated through inverse dynamics. Kinematic coordinates are
      represented using B-splines and modified by manipulating the control points. The
      iterative procedure stops and provides the final kinematic and kinetic estimates
      when a similarity criterion between estimated and measured ground reaction
      components is satisfied. The model structure was elaborated upon and the
      algorithm parameters optimized for robustness and accuracy using a benchmark
      motion in a simulation exercise. The maximal root mean square difference over
      time between estimated and benchmark quantities was approximately 1% of the peak
      to peak value for ground reaction components and intersegmental couples, and 6%
      for joint angles.

PMID- 15171633
TI  - [Help for the homeless].

PMID- 15171634
TI  - [Life style procedures against tuberculosis].

PMID- 15171636
TI  - [When the SIGNAL lamp goes on].

PMID- 15171635
TI  - [Electronic data systems in nursing].

PMID- 15171637
TI  - [What do I risk when I risk myself?].

PMID- 15171639
TI  - [New career opportunities in nursing].

PMID- 15171638
TI  - [Future-oriented nursing education].

PMID- 15171640
TI  - [Our neighbor in the east--the European Union waits].

PMID- 15171641
TI  - [Children suffer environmental burdens].

PMID- 15171642
TI  - [When you have packed, you don't want to go back].

PMID- 15171643
TI  - [When work clothes must be a uniform].

PMID- 15171644
TI  - [What nursing faculty must now know].

PMID- 15171645
TI  - [Politics are not meant for us nurses].

PMID- 15171646
TI  - [Comparison of genetic polymorphism of cytochrome CYP2C19 between men and women
      in Chinese population].
AB  - AIM: To assess the effect of gender on genetic polymorphism of cytochrome CYP2C19
      in Chinese population. METHODS: The genetic polymorphism of 140 healthy Chinese
      were analysed by PCR-RFLP (restriction fragment length polymorphism). RESULTS: Of
      52 genotyped male subjects, 23 (44.23%) were homozygous for wildtype (wt/wt), 6
      (11.54%) were homozygous for CYP2C19 m1 (m1/m1), and 23 (44.23%) were
      heterozygous for CYP2C19 m1 or CYP2C19 m2 (wt/m1 or wt/m2); and among the 88
      genotyped female subjects, 31 (35.23%) were homozygous for wildtype (wt/wt), 13
      (14.82%) were homozygous for CYP2C19 m1 (m1/m1), and 44 (50.0%) were heterozygous
      for CYP2C19 m1 or CYP2C19 m2 (wt/m1 or wt/m2); no homozygous genotype for CYP2C19
      m2 (m2/m2) was found in the study. CONCLUSION: There is no statistical difference
      in ocurance of wt/wt and m1/m1 between in male and in female, so gender have no
      significant effect on genetic polymorphism of cytochrome CYP2C19.

PMID- 15171647
TI  - [Establishment of high-throughput drug screening cell models based on JAK-STAT
      signal pathway].
AB  - AIM: To discover new drugs which may be applied to diseases of the immune system,
      hemogenesis system diseases and tumors, several high-throughput drug screening
      cell models based on JAK-STAT signal pathway have been established. METHODS: Four
      repeats of STAT DNA binding conserved sequences were synthesized, subcloned into
      pGL-Luc reporter vector and stably transfected into cell lines in vitro. Cell
      clones with high copy numbers of STAT binding sites and reporter genes were
      chosen as high-throughput drug screening cell models. The cell models were tested
      with known anti-allergic drugs and anti-tumor drugs by determining luciferase
      activity. The reaction was performed in 96 well micro-plates with a final volume
      of 50 microL. RESULTS: The cell models by performing rapid fluorescence assay
      were shown to be highly sensitive and stable after testing with cytokine and
      drugs. The modification of the expression plasmid simplified this method and made
      it more practical. It also provided good linear correlation, wide range of assay,
      highly sensitive and good reproducibility. CONCLUSION: The method can be
      performed by high-throughput drug screening for effective extraction of Chinese
      traditional herbs.

PMID- 15171649
TI  - Effect of crocetin on cardiac hypertrophy induced by overloading pressure in
      rats.
AB  - AIM: To study the influence of crocetin on cardiac hypertrophy induced by
      overloading pressure in rats. METHODS: The model of cardiac hypertrophy was
      produced by overloading pressure in rats. The animals were divided into five
      groups: sham-operation group (0.5% CMC-Na, ig), model group (operation + 0.5% CMC
      Na, ig), captopril group (operation + 50 mg x kg(-1), ig), crocetin I (100 mg x
      kg(-1), ig) and crocetin II (50 mg x kg(-1), ig). All animals were treated for 30
      d by ig. Then, cardiac indexes were examined. The activity of ATPase and the
      hydroxyproline content in heart were assayed by colorimetric analysis. Matrix
      metalloproteinases (MMPs) activity was assayed by SDS-PAGE zymography. RESULTS:
      Compared with the model group, crocetin was found to significantly reduce the
      cardiac indexes and the content of hydroxyproline in heart, increase the activity
      of Na+ , K+ -ATPase, Ca2+, Mg2+ -ATPase and inhibit MMPs activity. CONCLUSION:
      The activity of MMPs may play a key role in the cardiac hypertrophy induced by
      overloading pressure, and proprably as a result of decreasing the activity of
      MMPs. Crocetin was shown to prevent remodeling of cardiac hypertrophy induced by
      overloading pressure.

PMID- 15171648
TI  - [Activation of the immunologic function of rat Kupffer cells by the
      polysaccharides of Angelica sinensis].
AB  - AIM: To observe the influence of polysaccharides of Angelica sinensis (ASP) on
      the immunologic function of rat Kupffer cells. METHODS: Normal rat Kupffer cells
      were treated with ASP in vitro. Absorbance at 540 nm ( A540) of neutral red
      absorption and supernatant NO, TNF-alpha in the cells were measured to evaluate
      the immunologic function of Kupffer cells; LDH leakage was measured to estimate
      the severity of cellular damage; Rats were given ASP 0.025, 0.1, 0.25 and 1.0 g x
      kg(-1) ig (qd x 7 d) in vivo. The above indices and ACP of Kupffer cells were
      measured, sGST and sALT activity were detected as indices of hepatotoxicity.
      RESULTS: ASP markedly enhanced the phagocytic activity, ACP and supernatant NO,
      TNF-alpha of Kupffer cells both in vitro and in vivo . The increase of sGST was
      observed after administration of ASP 1.0 g x kg(-1), but the LDH leakage of the
      hepatocytes was not increased in vitro. CONCLUSION: ASP with suitable dose could
      activate the function of Kupffer cells. Slight liver injury was caused by ASP 1.0
      g x kg(-1) in vivo, which was likely caused by factors, such as NO, TNF-alpha,
      indirectly.

PMID- 15171650
TI  - [Anti-aging action of the total lactones of ginkgo on aging mice].
AB  - AIM: To investigate the effects of total lactones of ginkgo on aging by using D
      galactose induced aging mice and natural aging mice. METHODS: By using D
      galactose induced aging mice, to detect the LF content in heart and liver, the
      Hyp content in liver, the MAO, GSH-Px activities and the NO content in cerebrum.
      The apoptosis of cerebral cell was determined by terminal deoxy-nucleotidyl
      transforase-mediated dUTP-digoxigenin nick end-labeling (Tunel) in natural aging
      mice. RESULTS: TLG was shown to increase the GSH-Px activities, reduce the NO
      content and decrease the MAO activity in cerebrum. Meanwhile, TLG was found to
      reduce the LF content in liver and heart and raise the Hyp content in liver. TLG
      was shown to inhibit apoptosis of cerebral cell and decrease the number of
      apoptotic cells in the brain. CONCLUSION: TLG possesses effect on antiaging via
      attenuating lipid peroxidation and NO and apoptosis of cerebral cells.

PMID- 15171651
TI  - [Synthesis and anti-inflammatory analgesic activities of sinomenine derivatives].
AB  - AIM: To provide basic data for the synthesis of new sinomenine derivatives.
      METHODS: The C ring in sinomenine was modified. RESULTS: Seven compounds were
      prepared and screened for anti-inflammatory and analgesic activities. Compounds 2
      and 5 showed better activities. CONCLUSION: Modification of the C ring in
      sinomenine should be worthy to be studied further.

PMID- 15171652
TI  - [Synthesis and antibacterial activity of 7-(7-aminomethyl-5-azaspiro [2,4] hept-5
      yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
      and its analogues].
AB  - AIM: To find new antibacterial agents of quinolone with high activity and low
      toxicity. METHODS: To design and synthesize 7-(7-aminomethyl-5-azaspiro [2,4]
      hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3
      quinolinecarboxylic acid and its analogues, and to study their antibacterial
      activity in vitro and in vivo. RESULTS: Twenty new compounds (2 - 11, 17 - 26)
      were obtained including five targeted compounds (22 - 26). The structures of the
      compounds were confirmed by 1HNMR, MS and HRMS. Compounds 22 - 26 showed broad
      spectrum of antibacterial activity against Gram-positive and Gram-negative
      organisms. Especially for compound 24, the relevant MIC values for 13 strains of
      Gram-positive organisms were < 0.001 - 0.03 mg(-1), including 4 strains of S.
      pneumoniae, 2 strains of S. pyogenes, 3 strains of S. aureus and 2 strains of
      Enterococci which exhibited more potent activity than contrast agents
      (clinafloxacin and gatifloxacin). The MIC values of 24 for 6 strains Gram
      positive organisms were 0.01 - 1 mg x L(-1), which exhibited equal or lower
      activity than contrast agents. They were more effective than ciprofloxacin and
      gatifloxacin against intraperitoneal infections caused by S. pneumoniae and S.
      aureus in mice. CONCLUSION: Compounds (23, 24 and 26) showed excellent
      antibacterial activity in vitro and in vivo and should be worth further
      investigation.

PMID- 15171654
TI  - [Two new triterpenoid saponins from Lysimachia davurica].
AB  - AIM: To study the triterpenoid saponins in the whole plant of Lysimachia davurica
      Ledeb. METHODS: Column chromatography (including AB-8 macroporous resin, silica
      gel and ODS) was used to separate triterpenoid saponins whose structures were
      elucidated by ESI-MS, NMR (1D and 2D) and hydrolysis methods. RESULTS: Two new
      triterpenoid saponins were isolated and established as 3beta, 16alpha, 28
      trihydroxy-olean-12-en-3-0-(beta-D-glucopyranosyl-(1 --> 2)-beta-D
      glucuronopyranosyl)-28-0-beta-D-glucopyranoside) (I), 3beta, 16alpha, 28
      trihydroxy-olean-12-en-3-O-(beta-D-glucopyranosyl-(1 --> 2)-beta-D
      glucuronopyranosyl)-28-0-beta-D-glucopyranoside) (II). CONCLUSION: Compounds I
      and II are new compounds and named as davuricosides D and J.

PMID- 15171653
TI  - [Isolation and structure identification of the chemical constituents from pine
      needles of Pinus massoniana Lamb].
AB  - AIM: To study the chemical constituents of the water-extracts of the pine needles
      of Pinus massoniana Lamb.. METHODS: Pine needles were collected in Xixia country
      and extracted with boiling water for two times and the water-extracts were
      concentrated. The crude extract of pine needles was fractionated into four
      fractions by Et2O, EtOAc and n-BuOH. Various column chromatography with D-101
      macroreticular resin, Toyopearl HW-40 and silica gel were employed for the
      isolation and purification of compounds from the n-BuOH fraction of pine needles.
      The structures of the compounds were identified by physiochemical properties and
      spectral analysis (UV, IR, MS, 1HNMR, 13CNMR, DEPT, HMQC, HMBC, etc.). RESULTS:
      Four compounds were isolated from the n-BuOH fraction of water-extracts, and
      their structures were identified as 3-methoxyl-9'-O-alpha-L-rhamnopyranosyl
      4':7,5':8-diepoxyneoligan-4,9-diol (massonianoside E, I), 4,4',8,8',9
      pentahydroxyl-3,3'-dimethoxyl-7,9'-monoepoxylignan (II), umbelliferon (III), 4
      (4'-hydroxyl-3'-methoxylbenzyl)-2-butanone (IV). CONCLUSION: Compound I is a new
      compound, and compounds II, III and IV were isolated from this plant for the
      first time.

PMID- 15171656
TI  - [Study on the enantiomer separation of cetirizine dihydrochloride using
      proteinate- and amylose-based chiral stationary phase].
AB  - AIM: To study the chromatographic behavior of cetirizine dihydrochloride on the
      proteinate- and amylose- based chiral stationary phases so as to optimizate the
      chromatographic condition of its enantiomers separation. METHODS: When using
      amylose-based, alpha1-acid glycoprotein and ovomucoid protein chiral stationary
      phase, the mobile phase was hexane-isopropyl alcohol-alcohol-trifluoroacetic acid
      (430:45:25:1), acetonitrile-10 mmol x L(-1) phosphate buffer solution (adjusted
      to pH 7.0 with sodium hydroxide) (4:96) and acetonitrile-20 mmol x L(-1) KH, PO4
      solution (adjusted to pH 7.0 with triethylamine) (12.7:87.3), respectively. The
      temperature of proteinate column was 25 degrees C. The detective wavelength was
      230 nm. RESULTS: The two enantiomers could be separated on the two kinds of
      chiral stationary phases without derivatization and the resolution was above 2.0.
      The methods developed on the two kinds of chiral stationary phases are accurate,
      sensitive and specific. CONCLUSION: Both the proteinate- and amylose-based chiral
      stationary phases can be used to separate the enantiomers of cetirizine.

PMID- 15171655
TI  - [Studies on chemical constituents of Halenia elliptica guided by in vivo
      absorption and distribution of the constituents].
AB  - AIM: To investigate the chemical constituents of the Tibetan herbal medicine
      Halenia elliptica by guidance of in vivo absorption and distribution of the
      constituents. METHODS: HPLC with a diode array detector (DAD) and HPLC-MS were
      used for detecting the constituents of extracts of Halenia elliptica and animal
      samples. Several kinds of column chromatography were used for the isolation and
      purification of the main in vivo absorbed and distributed compounds from the
      extract of Halenia elliptica. RESULTS: Six main components detected in the
      extracts of the animal samples were isolated from the ethanolic extract of
      Halenia elliptica. CONCLUSION: After rats were treated with different extracts of
      Halenia elliplica, low polar components xanthone aglycon of Halenia elliptica
      were clearly observed in the extracts of liver, lipid, blood, hidney, heart and
      brain tissue of rats, while the polar components xanthone glycosides were
      detected in very small amounts in the animal samples. The xanthone glycosides can
      be decomposed into xanthone aglycons during the digestion, absorption and
      metabolism procedure. Therefore, the in vivo activity of the xanthone glycosides
      might be exhibited by their decomposed products. It is an accessibly valuable
      method to investigate chemical components of herbal medicines under the guidance
      by detecting in vivo absorption and distribution of chemical components of the
      herbal medicine extract.

PMID- 15171657
TI  - [Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy
      subjects].
AB  - AIM: To develop an HPLC-ESI-MS assay for determination of trimebutine in human
      plasma and to investigate the pharmacokinetics and bioequivalence of two
      trimebutine tablets in human. METHODS: After being made alkaline with saturated
      sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on
      a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium
      acetate buffer solution (pH 3.5)-methanol (18:82). HPLC-ESI-MS was performed in
      the selected ion monitoring (SIM) mode using target ions at m/z 388 for
      trimebutine and m/z 280 for the internal standard (sibutramine, IS). The
      fragmentor voltage was 50 V. A randomized cross-over design was performed in 20
      healthy volunteers. In the two study periods, a single 100 mg dose of each tablet
      was administered to each volunteer. RESULTS: Calibration curve was linear over
      the range of 0.3 - 150 microg x L(-1). The main pharmacokinetic parameters of
      T1/2, Tmax and Cmax were (9.2 +/- 2.8) h, (1.0 +/- 0.3) h and (40 +/- 20) microg
      x L(-1) for the reference tablet; (9.2 +/- 2.3) h, (0.9 +/- 0.4) h and (41 +/-
      20) microg x L(-1) for the test tablet. The relative bioavalability of the test
      tablet was (97 +/- 13)%. The results of variance analysis and two one-sided t
      test showed that there was no significant difference between the two formulations
      in the AUC and Cmax. CONCLUSION: The assay was proved to be sensitive, accurate
      and convenient. The two formulations were bioequivalent.

PMID- 15171659
TI  - [Study on distribution of safflor yellow A in tissues of mice].
AB  - AIM: To study the distributive character of safflor yellow A in mice. METHODS: A
      RP-HPLC method for the determination of safflor yellow A in tissues was
      established and applied to determine safflor yellow A in biological samples.
      RESULTS: After iv injection of Safflor yellow A in mice, the AUC of safflor
      yellow A was hightest in plasma, followed by kidney, liver, lung, heart, spleen.
      But it was not found in the brain. CONCLUSION: The distribution of safflor yellow
      A in the body is abroad and the speed of its process is swift.

PMID- 15171658
TI  - [Establishment of chromatographic fingerprint and quality assessment of Carthamus
      tinctorius L. by high performance liquid chromatography].
AB  - AIM: To establish chromatographic fingerprint of Carthamus tinctorius L. by RP
      HPLC in order to control the quality of Carthamus tinctorius L. METHODS: The
      gradient elution mode was applied in chromatographic separation, and data were
      analysed by "Computer Aided Similarity Evaluation" software to compare the
      quality of Carthamus tinctorius L. samples from different habitats. RESULTS:
      Samples from different habitats were of high similarity, though a few samples
      showed evident difference in fingerprint graphics. CONCLUSION: The RP-HPLC
      fingerprint method is repeatable, feasible in analysis of Carthamus tinctorius L.
      and can be used in quality assessment of Carthamus tinctorius L. Chemical
      components in Carthamus tinctorius L. samples from various habitats are similar,
      and their ratios between each other are stable.

PMID- 15171660
TI  - [Preparation of all-trans retinoic acid mixed micelles injection].
AB  - AIM: To increase the solubility and bioavailability of all-trans retinoic acid
      (ATRA). METHODS: Using the principle of lecthin/bile salt mixed micelle to
      prepared ATRA injection. The best formulation was obtained by the turbidity and
      three-phase figure. RESULTS: ATRA mixed micelles injection is stable. The average
      size of the mixed micelle is 17.8 nm, poly. index 0.495, zeta potential -16.5 mV.
      CONCLUSION: The method can be used to prepare the stable injection.

PMID- 15171662
TI  - [Study of the uptake of chitosan oligosaccharide nanoparticles by A549 cells].
AB  - AIM: To study the cellular uptake of chitosan oligosaccharide nanoparticles by
      A549 cells and evaluate the possibility of chitosan oligosaccharide nanoparticles
      used as a potential drug carrier. METHODS: Chitosan oligosaccharide (CSO) was
      obtained by ultrafiltration separation after regulation of the condition of
      chitosanase degradation. The molecular weight of CSO was determined by gel
      permeation chromatography (GPC). Chitosan oligosaccharide nanoparticles (CSO-NPs)
      were prepared by a novel solvent diffusion method in an oil system after the
      carrier material grafted fluorescein isothiocyanate (FITC) and the particle size
      distribution and zeta potential were determined by light scattering and
      electrophoretic mobility. The cytotoxicity and uptake of FITC-labeled CSO-NPs in
      A549 cells following various incubation periods were studied by the MTT method
      and fluorescence microscopy, flow cytometric analysis, respectively. RESULTS: The
      molecular weight (MW) of CSO was 18,678 u and the particles sizes of CSO-NPs were
      133.3 nm (number average) and 368.2 nm (volume average), respectively. The IC50
      of CSO and CSO-NPs were 944.36 and 643.16 mg x L(-1), respectively, and the
      result showed low cytotoxicity. Cellular uptake of CSO and CSO-NPs were relative
      to the concentration and the incubation time. Internalization of CSO-NPs
      increased 0.49 - 13.9 times more than that of the CSO with the same incubation
      time. CONCLUSION: CSO and CSO-NPs have low cytotoxicity. CSO-NPs can
      significantly improved the uptake of CSO-NPs by A549 cells compared to the same
      molecular weight of CSO.

PMID- 15171661
TI  - [Studies on design, synthesis and biodegradation of carrier for colon-site
      specific, drug delivery system].
AB  - AIM: To design and synthesize a novel vector for colon-site specific drug
      delivery system and investigate the relationship between the biodegradation
      properties and composition of materials in the simulated colon fluid. METHODS:
      The azocopolymer P (HEMA-MMA-MAA) was synthesized using 2
      hydroxyethylmethacrylate (HEMA), methyl methacrylate (MMA) and methacrylic acid
      (MAA) as comonmer, azobisisobutyronitrilel (AIBN) as initiator, cross-linked with
      divinylazobezene (DVAB). The chemical structure of the synthesized series of
      azocopolymer is examined by UV, FTIR spectroscopy and nuclear magnetic resonance
      data. Their swelling behavior is evaluated by the swelling equilibrium parameter
      Q, the biodegradation tests of the materials were carried out at physiologically
      relevant buffer designed to mimic the colon environment. The biodegradation
      properties were assessed using the differential scanning calorimeters (DSC) and
      gel permeation chromatography (GPC) and the morphology on the surface of
      materials before and after degradation was observed by scanning electron
      microscopy (SEM). RESULTS: The swelling equilibrium parameter Q increased with
      increasing the contents of HEMA and MAA in the materials. The degradation
      behavior was relevant to the ratio of three components in the copolymers.
      CONCLUSION: This materials may become a good carrier for the colon-site specific
      drug delivery system if the contents of commoners HEMA, MMA and MAA are adjusted
      reasonably.

PMID- 15171663
TI  - [Diffusion behaviors of drugs in thermosensitive in situ gels].
AB  - AIM: To study the diffusion behaviors of drugs in thermosensitive in situ gels,
      and provide valuable information for designing such delivery systems. METHODS: A
      free diffusion model was used to evaluate the effects of concentration, the
      property of drugs, as well as the gel compositions on the diffusivity of drugs.
      RESULTS: Drug transport through the aqueous channels of the gel followed Fickian
      mechanism, and no significant influence on the diffusivity was observed when the
      drug concentration was lowered from 5% to 0.25%. The diffusion coefficients of
      propranolol, timolol maleate, and salbutamol sulfate were 0.91, 1.32, and 3.30 x
      10(-6) cm2 x s(-1), respectively. The flux of hydrophilic drug was 3.6 fold
      faster than that of the lipophilic one implied the latter partitioned into the
      hydrophobic micellar core, and consequently the diffusion was retarded. The
      diffusivity was decreased with increased poloxamer and sodium hyaluronate
      concentration, due to the distorted aqueous channels and higher microviscosity.
      CONCLUSION: The result suggested that sustained release could be achieved for the
      thermosensitive in situ gel by incorporating lipophilic drug or increasing
      polymer concentration.

PMID- 15171664
TI  - [Targets and studies on anti-SARS drugs].

PMID- 15171665
TI  - Management of gastrointestinal disease. Returning it to primary care.

PMID- 15171666
TI  - Second thoughts on third-year training.

PMID- 15171667
TI  - Which test is best?

PMID- 15171668
TI  - Negative feedback for ALPHA form.

PMID- 15171669
TI  - Choosing our values.

PMID- 15171670
TI  - A prayer for deliverance. Life in rural family practice.

PMID- 15171672
TI  - Just the berries: Nephrotoxic drugs.

PMID- 15171671
TI  - Multivitamin supplements for pregnant women. New insights.
AB  - QUESTION: One of my patients is planning pregnancy and has started taking
      multivitamin supplements. She is experiencing gastric discomfort. What are the
      alternatives? ANSWER: Gastric discomfort is usually related to iron intake;
      pregnant women could use supplements with less iron. Pregnant women need 0.4 to
      1.0 mg of folic acid daily. If they have a family history of neural tube defects
      (NTDs), insulin-dependent diabetes mellitus, or epilepsy, or are currently taking
      valproic acid, carbamazepine, or antifolates (eg, sulfonamides), they are at
      intermediate-to-high risk of having babies with NTDs and need 4.0 to 5.0 mg of
      folic acid daily.

PMID- 15171673
TI  - Should thiazide diuretics be first-line therapy for high-risk hypertensive
      patients?

PMID- 15171674
TI  - Celiac disease. CME update for family physicians.
AB  - OBJECTIVE: To review current understanding of the epidemiology, pathophysiology,
      diagnosis, and management of celiac disease. QUALITY OF EVIDENCE: Few recent
      randomized controlled trials (level I evidence) have studied treatments for
      celiac disease. There are recent comparative studies (level II evidence) and
      there is well established consensus (level III evidence) on diagnosis and
      treatment of celiac disease. MAIN MESSAGE: Celiac disease is an immune-mediated
      small bowel enteropathy caused by exposure to wheat gluten protein. The disease
      can be insidious and often presents with only subtle extraintestinal
      manifestations in a variety of organ systems. Recent epidemiologic surveys
      suggest celiac disease is much more common in North America than previously
      thought. Advances in immunology and screening have made diagnosis more reliable
      than in the past. Removing gluten from the diet is effective in most cases.
      CONCLUSION: Celiac disease manifests subtly and is an easy diagnosis to miss.
      Good laboratory screening tests and effective treatment are available. Family
      practitioners should consider celiac disease in patients who present with
      confounding symptoms.

PMID- 15171675
TI  - How diet and lifestyle affect duodenal ulcers. Review of the evidence.
AB  - OBJECTIVE: To demonstrate the role of diet in reducing or aggravating risk of
      duodenal ulcer (DU). QUALITY OF EVIDENCE: MEDLINE was searched from January 1966
      to December 2001 for articles on the relationship between diet and lifestyle and
      DU using the key words duodenal ulcer and diet, fibre, or lifestyle. Evidence
      that these factors are associated with DU arose mainly from three case-control
      and three prospective studies (level II evidence) and from expert opinion (level
      III evidence). MAIN MESSAGE: A high-fibre diet appears to reduce risk of DU;
      soluble fibre might be associated with reduced risk also. Vitamin A intake is
      associated with lower risk of DU. Little evidence indicates that fat, type of
      fat, protein intake, or consumption of alcohol or caffeine affect the etiology of
      DU. CONCLUSION: A high-fibre diet, particularly if the fibre comes from fruit and
      vegetables, could reduce risk of DU; vitamin A might also be beneficial.

PMID- 15171676
TI  - Approach to managing elevated creatinine.
AB  - OBJECTIVE: To describe a systematic approach to finding the underlying cause of
      an elevated creatinine level. QUALITY OF EVIDENCE: This diagnostic approach is
      based on a synthesis of information from reference works on nephrology, articles
      found through a MEDLINE search, and the author's personal experience. MAIN
      MESSAGE: Elevated creatinine levels suggest the differential diagnosis of renal
      failure (RF). History and a complete physical examination are important, keeping
      in mind that RF is often asymptomatic in the early stages. After repeating the
      creatinine test to verify results, baseline tests should be ordered to identify
      the cause of the RF. Comparing results of serial tests is essential for
      determining whether RF is acute or chronic, stable or progressive. An ultrasound
      scan is particularly useful for eliminating an obstructive cause; the size of the
      kidney can indicate whether disease is acute or chronic. Complementary blood
      tests and imaging studies might be useful. CONCLUSION: Diagnosing and managing RF
      can appear complex, but a systematic approach will help you find the cause and
      treat the condition.

PMID- 15171677
TI  - Vitamin B12 deficiency. Prevalence among South Asians at a Toronto clinic.
AB  - OBJECTIVE: To estimate the prevalence of vitamin B12 deficiency in adult South
      Asian patients. DESIGN: Retrospective chart review. SETTING: Family practice
      clinic in Toronto, Ont. PARTICIPANTS: Records of 988 South Asian patients.
      INTERVENTION: Of 1000 randomly selected records, we found 988 charts. From charts
      with at least one documented B12 level, we extracted data on age, mean
      corpuscular volume (MCV), hemoglobin and ferritin levels, and diet (if
      available). Descriptive and analytic statistics were calculated. MAIN OUTCOME
      MEASURES: Levels of serum B12 and factors associated with low levels of B12.
      RESULTS: B12 results were documented in 49% of charts; 46% of results showed
      deficiency. Patients older than 65 and vegetarians were more likely to be B12
      deficient. Low serum B12 levels were positively correlated with low hemoglobin
      and ferritin levels and poorly correlated with low MCV levels. CONCLUSION: Many
      more South Asian patients than patients in the general population have vitamin
      B12 deficiency. A vegetarian diet seems a strong risk factor. A single low
      result, however, might not indicate true B12 deficiency.

PMID- 15171678
TI  - Chronic obstructive pulmonary disease. Family physicians' role in management.

PMID- 15171679
TI  - One resident's view on the shortage of rural physicians.

PMID- 15171681
TI  - Heterodimeric interaction and interfaces of S100A1 and S100P.
AB  - With the widespread use of yeast two-hybrid systems, many heterodimeric forms of
      S100 proteins have been found, although their biological significance is unknown.
      In the present study, S100A1 was found to interact with another S100 protein,
      S100P, by using the yeast two-hybrid system. The binding parameters of the
      interaction were obtained using an optical biosensor and show that S100P has a
      slightly higher affinity for S100A1 (K(d)=10-20 nM) when compared with that for
      self-association (K(d)=40-120 nM). The physical interaction of S100A1 and S100P
      was also demonstrated in living mammalian cells using a fluorescence resonance
      energy transfer technique. Preincubation of recombinant S100P with S100A1, before
      the biosensor assay, reduced by up to 50% the binding of S100P to a recombinant C
      terminal fragment of non-muscle myosin A, one of its target molecules. Site
      specific mutations of S100P and S100A1, combined with homology modelling of an
      S100P/S100A1 heterodimer using known S100P and S100A1 structures, allowed the
      hydrophobic interactions at the dimeric interface of the heterodimer to be
      defined and provide an explanation for the heterodimerization of S100P and S100A1
      at the molecular level. These results have revealed the similarities and the
      differences between the S100P homodimer and the S100A1/S100P heterodimer.

PMID- 15171682
TI  - Lysophosphatidic acid attenuates the cytotoxic effects and degree of peroxisome
      proliferator-activated receptor gamma activation induced by 15-deoxyDelta12,14
      prostaglandin J2 in neuroblastoma cells.
AB  - PPARgamma (peroxisome proliferator-activated receptor gamma) is a ligand
      activated transcription factor that responds to 15dPGJ2 (15-deoxy-Delta12,14
      prostglandin J2). 15dPGJ2, in vitro, halts neuroblastoma cell growth, but
      reported mechanisms vary. Here we evaluated the modulatory effects of endogenous
      serum lipid mitogens upon the extent of 15dPGJ2-induced growth inhibition and on
      the precise cellular responses of neuroblastoma cells to PPARgamma activation. We
      show that 15dPGJ2 specifically inhibited cell growth in both complete and
      delipidated media. 15dPGJ2-induced growth inhibition was accompanied by decreased
      cell viability, although the effect was far more marked in delipidated medium
      than in complete medium. Incubation with 15dPGJ2 in complete medium resulted in
      cytoplasmic changes characteristic of type II programmed cell death (autophagy),
      while prior serum lipid removal resulted in cell death via an apoptotic
      mechanism. These distinct, serum lipid-dependent cellular responses to 15dPGJ2
      were accompanied by increases in the expression of a reporter gene construct
      containing a PPAR response element of 2.3-fold in complete medium, but of 4.8
      fold in delipidated medium. Restoration of the serum lysolipid LPA
      (lysophosphatidic acid) to cells in delipidated medium reduced 15dPGJ2-mediated
      PPARgamma activation, growth inhibition and cell death; following addition of S1P
      (sphingosine 1-phosphate), decreases were apparent but more marginal. Further,
      while the effects of LPA in delipidated medium were mediated through a
      G(i)/phosphoinositide 3-kinase/MAPK (mitogen-activated protein kinase) pathway,
      those of S1P did not involve the MAPK component. These data suggest that the
      serum lysolipid LPA modulates the degree of PPARgamma activation and the precise
      cellular response to 15dPGJ2 via activation of a G(i)/phosphoinositide 3
      kinase/MAPK pathway.

PMID- 15171684
TI  - Oestrogens and temperature-dependent sex determination in reptiles: all is in the
      gonads.
AB  - In many species of oviparous reptiles, the first steps of gonadal sex
      differentiation depend on the incubation temperature of the eggs. Feminization of
      gonads by exogenous oestrogens at a male-producing temperature and
      masculinization of gonads by antioestrogens and aromatase inhibitors at a female
      producing temperature have irrefutably demonstrated the involvement of oestrogens
      in ovarian differentiation. Nevertheless, several studies performed on the entire
      gonad/adrenal/mesonephros complex failed to find differences between male- and
      female-producing temperatures in oestrogen content, aromatase activity and
      aromatase gene expression during the thermosensitive period for sex
      determination. Thus, the key role of aromatase and oestrogens in the first steps
      of ovarian differentiation has been questioned, and extragonadal organs or
      tissues, such as adrenal, mesonephros, brain or yolk, were considered as possible
      targets of temperature and sources of the oestrogens acting on gonadal sex
      differentiation. In disagreement with this view, experiments and assays carried
      out on the gonads alone, i.e. separated from the adrenal/mesonephros, provide
      evidence that the gonads themselves respond to temperature shifts by modifying
      their sexual differentiation and are the site of aromatase activity and oestrogen
      synthesis during the thermosensitive period. Oestrogens act locally on both the
      cortical and the medullary part of the gonad to direct ovarian differentiation.
      We have concluded that there is no objective reason to search for the implication
      of other organs in the phenomenon of temperature-dependent sex determination in
      reptiles. From the comparison with data obtained in other vertebrates, we propose
      two main directions for future research: to examine how transcription of the
      aromatase gene is regulated and to identify molecular and cellular targets of
      oestrogens in gonads during sex differentiation, in species with strict genotypic
      sex determination and species with temperature-dependent sex determination.

PMID- 15171683
TI  - A core catalytic domain of the TyrA protein family: arogenate dehydrogenase from
      Synechocystis.
AB  - The TyrA protein family includes prephenate dehydrogenases, cyclohexadienyl
      dehydrogenases and TyrA(a)s (arogenate dehydrogenases). tyrA(a) from
      Synechocystis sp. PCC 6803, encoding a 30 kDa TyrA(a) protein, was cloned into an
      overexpression vector in Escherichia coli. TyrA(a) was then purified to apparent
      homogeneity and characterized. This protein is a model structure for a catalytic
      core domain in the TyrA superfamily, uncomplicated by allosteric or fused
      domains. Competitive inhibitors acting at the catalytic core of TyrA proteins are
      analogues of any accepted cyclohexadienyl substrate. The homodimeric enzyme was
      specific for L-arogenate (K(m)=331 microM) and NADP+ (K(m)=38 microM), being
      unable to substitute prephenate or NAD+ respectively. L-Tyrosine was a potent
      inhibitor of the enzyme (K(i)=70 microM). NADPH had no detectable ability to
      inhibit the reaction. Although the mechanism is probably steady-state random
      order, properties of 2',5'-ADP as an inhibitor suggest a high preference for L
      arogenate binding first. Comparative enzymology established that both of the
      arogenate-pathway enzymes, prephenate aminotransferase and TyrA(a), were present
      in many diverse cyanobacteria and in a variety of eukaryotic red and green algae.

PMID- 15171685
TI  - Endothelium-dependent responses in human isolated thyroid arteries from donors.
AB  - The functional properties of the endothelium of human thyroid arteries remain
      unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin
      (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses
      to acetylcholine and noradrenaline in isolated thyroid arteries obtained from
      multi-organ donors. Artery rings were suspended in organ baths for isometric
      recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium
      dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl
      L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively.
      Acetylcholine induced concentration-dependent relaxation; this effect was not
      modified by indomethacin and was only partly reduced by L-NMMA, but was abolished
      in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA
      was abolished by using either apamin combined with charybdotoxin, ouabain plus
      barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent
      contractions which were of greater magnitude in arteries denuded of endothelium
      or in the presence of L-NMMA. In conclusion, the results indicate that in human
      thyroid arteries the endothelium significantly modulates responses to
      acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a
      dominant role in acetylcholine-induced relaxation through activation of Ca(2+)
      activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.

PMID- 15171686
TI  - Comparative kinetic characterization of rat thyroid iodotyrosine dehalogenase and
      iodothyronine deiodinase type 1.
AB  - The initial characterization of a thyroid iodotyrosine dehalogenase (tDh), which
      deiodinates mono-iodotyrosine and di-iodotyrosine, was made almost 50 years ago,
      but little is known about its catalytic and kinetic properties. A distinct group
      of dehalogenases, the so-called iodothyronine deiodinases (IDs), that
      specifically remove iodine atoms from iodothyronines were subsequently discovered
      and have been extensively characterized. Iodothyronine deiodinase type 1 (ID1) is
      highly expressed in the rat thyroid gland, but the co-expression in this tissue
      of the two different dehalogenating enzymes has not yet been clearly defined.
      This work compares and contrasts the kinetic properties of tDh and ID1 in the rat
      thyroid gland. Differential affinities for substrates, cofactors and inhibitors
      distinguish the two activities, and a reaction mechanism for tDh is proposed. The
      results reported here support the view that the rat thyroid gland has a
      distinctive set of dehalogenases specialized in iodine metabolism.

PMID- 15171688
TI  - Expression of thyrotropin-releasing hormone receptor in immortalized beta-cell
      lines and rat pancreas.
AB  - Thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide, is expressed in
      pancreatic islets at peak levels during the late gestation and early neonate
      period. TRH increases insulin production in cultured beta-cells, suggesting that
      it might play a role in regulating pancreatic beta-cell function. However, there
      is limited information on TRH receptor expression in the pancreas. The aim of the
      present study was to explore the distribution of the TRH receptor in the pancreas
      and its function in pancreatic beta-cells. TRH receptor type 1 (TRHR1) gene
      expression was detected by RT-PCR and verified by Northern blotting and
      immunoblotting in the beta-cell lines, INS-1 and betaTC-6, and the rat pancreatic
      organ. The absence of TRH receptor type 2 expression in the tissue and cells
      indicated the tissue specificity of TRH receptor expression in the pancreas. The
      TRHR1 signals (detected by in situ hybridization) were distributed not only in
      islets but also in the surrounding areas of the pancreatic ductal and vasal
      epithelia. The apparent dissociation constant value for the affinity of [(3)H]3
      methyl-histidine TRH (MeTRH) is 4.19 in INS-1 and 3.09 nM in betaTC-6. In
      addition, TRH induced epidermal growth factor (EGF) receptor phosphorylation with
      a half-maximum concentration of approximately 50 nM, whereas the high affinity
      analogue of TRH, MeTRH, was 1 nM. This suggested that the affinity of TRH ligands
      for the TRH receptor influences the activation of EGF receptor phosphorylation in
      betaTC-6 cells. Our observations suggested that the biological role of TRH in
      pancreatic beta-cells is via the activation of TRHR1. Further research is
      required to identify the role of TRHR1 in the pancreas aside from the islets.

PMID- 15171687
TI  - Activities of UDP-glucuronyltransferase, beta-glucuronidase and deiodinase types
      I and II in hyper- and hypothyroid rats.
AB  - We have investigated the hypothesis that uridine 5'-diphosphate (UDP)
      glucuronyltransferases (UGTs) and beta-glucuronidase are jointly involved in a
      mechanism for the storage and mobilization of iodothyronine metabolites in liver,
      kidney, heart and brain. Specifically, we predicted UGT activities to decrease
      and increase respectively, and beta-glucuronidase activity to increase and
      decrease respectively in hypo- and hyperthyroidism. To this end we have studied
      the effects of thyroid status on the activities of different enzymes involved in
      thyroid hormone metabolism in liver, kidney, heart and brain from adult rats with
      experimentally induced hypo- and hyperthyroidism. We used whole organ homogenates
      to determine the specific enzyme activities of phenol- and androsteron-UGT, beta
      glucuronidase, as well as iodothyronine deiodinase types I and II. Deiodinase
      type I activities in liver and kidney were decreased in hypothyroid animals and,
      in liver only, increased in hyperthyroidism. Deiodinase type II activity was
      increased in hyperthyroid rat kidney only. Interestingly, in the heart,
      deiodinase type I-specific activity was increased fourfold, although the increase
      was not statistically significant. Cardiac deiodinase type I activity was
      detectable but not sensitive to thyroid status. Hepatic phenol-UGT as well as
      androsteron-UGT activities were decreased in hypothyroid rats, with specific
      androsteron-UGT activities two to three orders of magnitude lower than phenol-UGT
      activities. Both UGT isozymes were well above detection limits in heart, but
      appeared to be insensitive to thyroid status. In contrast, cardiac beta
      glucuronidase activity decreased in hypothyroid tissue, whereas the activity of
      this enzyme in the other organs investigated did not change significantly. In
      summary, cardiac beta-glucuronidase, albeit in low levels, and hepatic phenol-UGT
      activities were responsive only to experimental hypothyroidism. Although a high
      basal activity of the pleiotropic beta-glucuronidase masking subtle activity
      changes in response to thyroid status cannot be ruled out, we conclude that
      hepatic, renal and cardiac UGT and beta-glucuronidase activities are not
      regulated reciprocally with thyroid status.

PMID- 15171689
TI  - Relationship of plasma extracellular-superoxide dismutase level with insulin
      resistance in type 2 diabetic patients.
AB  - Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein located
      in blood vessel walls at high levels and may be important in the antioxidant
      capability of vascular walls. The aim of this study was to assess plasma levels
      of EC-SOD and to evaluate the relationship of the EC-SOD level with insulin
      resistance in type 2 diabetic patients. We determined plasma EC-SOD in 122
      patients and found for the first time that the EC-SOD level was strongly and
      positively related to adiponectin (r=0.503, P < 0.001), and significantly and
      inversely related to fasting plasma glucose (FPG) (r=-0.209, P=0.022), body-mass
      index (BMI) (r=-0.187, P=0.040) and homeostasis model assessment-insulin
      resistance index (HOMA-R) (r=-0.190, P=0.039). Stepwise-multiple regression
      analysis also showed a significant influence of adiponectin (F=33.27) on the EC
      SOD level. Administration of pioglitazone to 19 diabetic patients significantly
      increased the plasma levels of EC-SOD (69.9+/-19.3 ng/ml to 97.4+/-25.9 ng/ml; P
      < 0.0001) and adiponectin, while it decreased tumor necrosis factor-alpha (TNF
      alpha). The present observations suggest that factors related to the pathogenesis
      of insulin resistance play an important role in the regulation of the plasma EC
      SOD concentration. It is possible that the increase in the EC-SOD level by
      pioglitazone administration in diabetic patients is due to a decline of TNF
      alpha, which is known to suppress EC-SOD expression.

PMID- 15171690
TI  - Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic
      patients.
AB  - An inflammatory process may be involved in nitric oxide production in skeletal
      muscle of type 2 diabetic patients. Nitric oxide generation in skeletal muscle
      was assessed in 14 non-complicated type 2 diabetic patients and in 12 healthy
      subjects. In samples of quadriceps femoris muscle, endothelial nitric oxide
      synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrite, nitrate and
      nitrotyrosine were determined. The macrophage-specific antigen CD163, the T-cell
      membrane factor CD154 and tumour necrosis factor-alpha (TNF-alpha) were also
      assayed. In six patients, ultrastructural analysis of muscle was performed.
      Nitrites and nitrates were increased in patients as compared to controls (22.7+/
      4.5 and 32.7+/-7.0 vs 16.0+/-2.9 and 22.8+/-4.0 micromol/mg protein; P<0.001,
      Mann-Whitney U test). Endothelial NOS was similar in diabetic and control
      subjects (36.4+/-13.8 vs 36.3+/-6.8 ng/mg protein), contrasting with the
      significant increase of iNOS recorded in patients (34.3+/-13.0 vs 8.5+/-2.8 ng/mg
      protein, P<0.00002). Nitrotyrosine levels were higher in the patient than in the
      control group (42.1+/-24.4 vs 10.3+/-2.5 ng/mg protein, P<0.00002), as were CD163
      (10-fold) and TNF-alpha (fourfold) levels. Furthermore, CD154 levels were
      detectable only in the patient samples (10.2+/-5.3 ng/mg protein). By multiple
      regression analysis, changes in glycated haemoglobin values could predict 96%
      variation in nitrotyrosine. Macrophages were present in all muscle samples
      analysed by electromicroscopy. The increased levels of CD163, CD154 and TNF-alpha
      indicate that an inflammatory process occurs in skeletal muscle of type 2
      diabetic patients. This may contribute to iNOS induction, muscle damage and
      insulin resistance.

PMID- 15171691
TI  - Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment
      with an aldose reductase inhibitor.
AB  - An accelerated polyol pathway in diabetes contributes to the development of
      diabetic complications. To elucidate diabetic nephropathy involving also renal
      tubular damage, we measured urinary sorbitol concentration concomitantly with
      urinary N-acetyl-D-glucosaminidase (NAG) excretion in WBN-kob diabetic
      rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic
      rats in parallel with whole blood sorbitol concentrations. An increase in 24-h
      urinary NAG excretion coincided with the elevated urinary sorbitol levels in the
      diabetic rats. The administration of epalrestat, an aldose reductase inhibitor,
      reduced the increased whole blood and urinary sorbitol concentrations and urinary
      NAG excretion concomitantly with renal aldose reductase inhibition in the
      diabetic rats. These results indicate that diabetic nephropathy involves
      distorted cell function of renal tubules, and that treatment with epalrestat may
      prevent at least the progress of the nephropathy.

PMID- 15171692
TI  - Protein tyrosine phosphatase 1B is located with glucagon vesicles, and its
      concentration is inversely correlated with the rate of glucagon secretion of
      INR1G9 cells.
AB  - High concentrations of protein tyrosine phosphatase (PTP) were found with
      secretory vesicles of glucagon-producing INR1G9 cells by electron microscopic
      immunocytochemistry, using a polyclonal antiserum specific for the PTP1B/T-cell
      (TC)PTP subfamily of PTP. Since TCPTP protein and mRNA were below the detection
      limit in the cells but significant amounts of PTP1B and mRNA were recognised by a
      specific monoclonal antibody and a mRNA probe we conclude, that the PTP
      associated with the vesicles is PTP1B. Only reverse transcriptase (RT)-PCR with
      primers specific for PTP1B yielded a product of the expected nucleotide sequence.
      Thus, we conclude that the PTP associated with the vesicles is PTP1B. The
      presence of vanadate for 48 h attenuated PTP1B expression and caused reduction of
      steady-state levels of the phosphatase. These conditions also led to a continuing
      increase in the steady-state rate of glucagon release by the cells. This rate and
      tyrosine phosphatase levels showed an inverse relationship, suggesting a
      suppressive role of PTP1B on the regulated secretion of glucagon by INR1G9 cells.

PMID- 15171693
TI  - Human milk induces fetal small intestinal cell proliferation - involvement of a
      different tyrosine kinase signaling pathway from epidermal growth factor
      receptor.
AB  - Breast milk has non-nutritional protective effects on recipient infants. It has
      been speculated that bioactive substances present in human milk have important
      roles in protecting infants. However, the mechanisms by which such substances
      protect newborns are unclear. Therefore, we analyzed the growth-promoting
      activity of human milk and the intracellular signaling mechanism thereof using
      human fetal small intestinal (FHS 74 Int) cells. Epidermal growth factor (EGF)
      stimulated the proliferation of these cells. However, this stimulation was less
      effective than that of aqueous milk (5% vol/vol). The bioactivity of human milk
      was heat stable but protease sensitive. EGF receptor tyrosine kinase inhibitor
      did not repress the milk-induced growth-promoting effect on fetal small
      intestinal cells. Regarding the intracellular signaling pathway, the milk-induced
      cell proliferation pathway was tyrosine kinase dependent but was neither mitogen
      activated protein (MAP) kinase nor phosphatidylinositol-3 (PI-3) kinase
      dependent. On the other hand, EGF-induced cell proliferation was tyrosine kinase,
      MAP kinase, and PI-3 kinase dependent. Rapid tyrosine phosphorylation of several
      intracellular proteins was detected after milk stimulation. Furthermore, the time
      course of phosphorylation induced by milk was different from that induced by EGF.
      The sizes of the proteins phosphorylated in response to milk were different from
      those of the Shc proteins phosphorylated in response to EGF. These results
      suggest that human milk induces fetal intestinal cell proliferation through a
      unique tyrosine kinase pathway different from the EGF receptor signaling pathway.

PMID- 15171694
TI  - Postnatal insulin secretion and sensitivity after manipulation of fetal growth by
      embryo transfer in the horse.
AB  - This study examined the effects of intrauterine growth on insulin secretion and
      resistance in newborn foals. Embryo transfer between small pony and large
      Thoroughbred mares was used to produce four groups of foals with different birth
      weights (pony in pony n=7; pony in Thoroughbred n=7; Thoroughbred in Thoroughbred
      n=8; Thoroughbred in pony n=8). On day 2 after birth, glucose (0.5 g/kg) was
      administered intravenously to the foal and blood samples were taken for 2 h to
      determine plasma glucose and insulin concentrations. On day 3, insulin
      sensitivity was assessed by giving insulin (0.75 U/kg i.v.) and measuring the
      decrement in plasma glucose in the foals. There were no significant differences
      in insulin secretion, insulin sensitivity or glucose tolerance between the
      control and growth-retarded Thoroughbred foals. Overgrown pony foals delivered by
      Thoroughbred mares had higher basal insulin levels and greater beta cell
      responses to glucose than the other groups of foals. The relationship between
      plasma glucose and insulin was also significantly steeper in overgrown pony foals
      than in the other groups. Variations in intrauterine growth rate, therefore,
      affect postnatal insulin secretion in the horse. More specifically, it is
      overgrowth, not growth retardation in utero that alters equine beta cell function
      in the immediate neonatal period.

PMID- 15171695
TI  - Development of insulin and proinsulin secretion in newborn pony foals.
AB  - At birth, the endocrine pancreas must assume a glucoregulatory role if the
      neonate is to survive the transition from parenteral to enteral nutrition. In
      species like the horse, neonatal hypoglycaemia is common, which suggests that the
      glucoregulatory mechanisms are not always fully competent at birth. Hence, this
      study examined pancreatic beta cell function in newborn foals during nutritional
      adaptation over the first 10 days post partum. Over a 48 h period at three time
      intervals after birth (days 1-2, 5-6 and 9-10 post partum), the beta cell
      responses to suckling and to intravenous administration of glucose, arginine and
      saline were measured in seven normal pony foals. Basal plasma concentrations of
      proinsulin, but not insulin or glucose, increased significantly between days 1
      and 10. Suckling caused a gradual increase in plasma glucose, which was
      accompanied by a significant increase in plasma insulin concentrations 15 min
      after the onset of suckling on days 5 and 9, but not day 1. There was no
      significant change in plasma proinsulin concentrations in response to suckling at
      any age. At all ages studied, glucose and arginine administration stimulated an
      increase in the plasma concentrations of insulin and proinsulin; these beta cell
      responses did not change significantly with postnatal age. The insulin responses
      to glucose were significantly greater than those of arginine at each time period.
      Glucose clearance was significantly slower on day 1 than subsequently. Proinsulin
      and glucose, but not insulin, concentrations decreased significantly after saline
      administration at all three ages. At each time period, there was a significant
      positive relationship between the plasma insulin and proinsulin concentrations,
      the slope of which was significantly shallower on days 1-2 than subsequently.
      These results show that equine beta cells are responsive to glucose and arginine
      and release both insulin and proinsulin during the immediate postnatal period.
      They also suggest that newborn foals may be insulin resistant on the first day
      after birth.

PMID- 15171696
TI  - Role of leukemia inhibitor factor (LIF) in decidualisation of murine uterine
      stromal cells in vitro.
AB  - Decidualisation of uterine stromal cells is a prerequisite for implantation of
      the embryo in mice. Here we have used an in vitro culture system in which stromal
      cells decidualise as indicated by a number of markers, including an increase in
      alkaline phosphatase (ALP) activity. The latter was used as a quantitative marker
      of decidualisation in the presence of low (2%) fetal calf serum. Prostaglandin
      E(2) (PGE(2)), which is known to induce decidualisation, increased ALP activity,
      and this effect was blocked in a dose-dependent manner by indomethacin. Leukemia
      inhibitory factor (LIF) was then examined, but it had no effect on PGE(2)
      secretion. However, LIF suppressed ALP activity in a dose-dependent manner in the
      presence of 2% serum, while an inhibitor of LIF that competes for binding to its
      receptor reversed the effect of LIF and increased ALP activity above the control
      level. In serum-free cultures, stromal cells differentiated rapidly, and no
      differences were observed between LIF-treated and untreated cultures. Stromal
      cells produce LIF during in vitro culture, and this peaked at 48 h. Freshly
      collected stromal cells from both day-2 and -4 pregnant mice expressed mRNA for
      the LIF receptor, and the transcript level was higher in cells isolated on day 4.
      However, no differences were observed in the relative levels of transcripts in
      cells from day 2 and day 4 after culture, nor were there differences between the
      LIF-treated cultures and controls. Therefore, in this study, we have shown that
      LIF suppresses decidualisation of murine uterine stromal cells in the presence of
      serum, this is not due to the regulation of PGE(2) secretion by stromal cells.

PMID- 15171698
TI  - Glucocorticoid counteracts the suppressive effect of tumor necrosis factor-alpha
      on the surge of luteinizing hormone secretion in rats.
AB  - We have previously reported that tumor necrosis factor-alpha (TNF-alpha)
      suppressed pulsatile secretion of luteinizing hormone (LH) in adrenalectomized
      (ADX) rats, which was restored by replacement of glucocorticoid. In the present
      study, we examined the role of glucocorticoid in inducing the preovulatory LH
      surge under conditions of infectious stress. Intravenous injection of TNF-alpha
      (1 microg) into the proestrous rats at 1300 h attenuated the LH surge and
      decreased the number of oocytes ovulated. The inhibitory effect of TNF-alpha on
      the LH surge was blocked by pretreatment with indomethacin, suggesting that the
      effects of TNF-alpha were mediated by prostaglandins (PGs). On the other hand,
      ADX markedly enhanced the inhibitory effect of TNF-alpha on the LH surge and
      subsequent ovulation, which was almost completely restored by pretreatment with a
      subcutaneous injection of corticosterone (10 mg). These results suggest that
      glucocorticoid counteracts the inhibitory effect of the cytokines on the
      preovulatory LH surge by suppressing PG synthesis, and thereby helps to maintain
      reproductive function under infectious stress conditions.

PMID- 15171697
TI  - Reduction of rat prostate weight by combined quercetin-finasteride treatment is
      associated with cell cycle deregulation.
AB  - Benign prostate hyperplasia and prostate cancer are major public health problems.
      We report herein that daily treatment of male rats with 50, 100 or 150 mg
      quercetin per kg body weight resulted in serum concentrations of quercetin
      equivalent to 25.3 microM, 43.3 microM and 54.3 microM respectively.
      Concomitantly, serum testosterone levels were increased by 1.79-, 1.83- and 3.48
      fold, while serum dihydrotestosterone (DHT) levels were 125%, 92% and 73% of the
      control. A slight increase in prostate weight coupled with dilated prostate
      lumens full of secretory materials were observed. Finasteride alone caused a
      significant decrease in serum DHT level and prostate weight. Co-administration of
      quercetin with finasteride prevented the finasteride-induced decrease in serum
      DHT levels but significantly enhanced the reduction in wet prostate weight, which
      was reduced by 26.9% in finasteride-treated animals to 31.8%, 40.0% and 48.2%
      after finasteride given together with the three doses of quercetin. The combined
      treatment altered cell cycle-regulated proteins in a wide spectrum. The
      expressions of cyclin D1, CDK-4, cdc-2 and phospho-cdc-2 at tyrosine 15, phospho
      MEK1/2, phospho-MAP kinase, phospho-pRb at serine 780 and serine 807/811 were
      significantly inhibited, while the levels of p15, p21 and p27 were increased. In
      conclusion, quercetin-finasteride treatments caused wide cell cycle deregulation
      in rat prostates, which, in turn, decreased the proliferation rate, changed the
      secretion activities of epithelial cells and resulted in a marked reduction in
      wet prostate weight. The results suggest that quercetin synergizes with
      finasteride to reduce the wet prostate weight through a cell cycle-related
      pathway, which may be androgen independent.

PMID- 15171699
TI  - Differential responses of the hypothalamo-pituitary-adrenocortical axis to acute
      restraint stress in Hatano high- and low-avoidance rats.
AB  - The high- and low-avoidance animal (HAA and LAA respectively) strains of Hatano
      rats were originally selected and bred from Sprague-Dawley rats for their
      performance in the shuttle-box task. The present study focused on the activity of
      the hypothalamo-pituitary-adrenocortical (HPA) axis of HAA and LAA rats in
      response to restraint stress. The restraint stress induced an elevation in plasma
      concentrations of ACTH, prolactin, corticosterone and progesterone. Peak levels
      of plasma ACTH during stress conditions were significantly higher in HAA rats
      than in LAA rats, while peak levels of prolactin were significantly lower in HAA
      rats than in LAA rats. Under stress conditions, ACTH and prolactin synthesis in
      the anterior pituitary glands was significantly higher in HAA rats compared with
      LAA rats. The peak plasma concentrations of corticosterone, during restraint
      stress, were significantly higher in LAA rats compared with HAA rats. These
      results indicate that the response of the hypothalamo-pituitary axis to acute
      restraint stress is greater in HAA rats than in LAA rats, whereas the ACTH
      induced adrenal response of corticosterone release is higher in LAA rats than in
      HAA rats. On the other hand, prolactin secretory activity is higher in LAA rats
      compared with HAA rats. These differences in endocrine responses to stress may be
      involved in the regulation of the avoidance responses in the shuttle-box task.

PMID- 15171700
TI  - Pituitary mitosis and apoptotic responsiveness following adrenalectomy are
      independent of hypothalamic paraventricular nucleus CRH input.
AB  - We have previously identified a series of age-dependent, temporally constrained
      and closely interdependent mitotic and apoptotic events in the male rat anterior
      pituitary that occur in response to timed single and repeated hypothalamo
      pituitary-adrenal axis stimuli. One of the most dramatic of these is the short
      burst of apoptosis that occurs 24-48 h after exposure to dexamethasone. If
      bilateral adrenalectomy precedes exposure to dexamethasone by 1-2 weeks, mitotic
      activity is transiently increased and the subsequent apoptotic response to
      dexamethasone greatly enhanced. This study was designed to determine whether
      adrenalectomy-induced augmentation of the apoptotically sensitive pituitary cell
      population is mediated via glucocorticoid withdrawal at the level of the
      pituitary, or whether increased exposure to hypothalamo-hypophyseal trophic
      hormones of paraventricular origin is responsible. We used stereotaxic surgery to
      isolate both paraventricular nuclei without disturbing either median eminence
      input from the arcuate and supraoptic nuclei, or the hypothalamo-hypophyseal
      portal blood flow that carries a significant proportion of the pituitary systemic
      supply. When bilateral adrenalectomy and paraventricular nucleus disconnection
      were combined, the adrenalectomy-induced increase in anterior pituitary pro
      opiomelanocortin (POMC) transcript prevalence was abolished, confirming the loss
      of paraventricular corticotrophin-releasing hormone (CRH) input. However, the
      amplitude and pattern of the adrenalectomy-induced anterior pituitary mitotic
      response and enhancement of the apoptotic response to dexamethasone 1 week later
      remained completely intact. These data demonstrate that anterior pituitary
      trophic responses following bilateral adrenalectomy are more likely to be
      mediated through direct glucocorticoid withdrawal at the level of the pituitary
      rather than via changes in hypothalamo-hypophyseal releasing factor exposure.
      This finding highlights the presence of distinct control systems for pituitary
      hormone gene expression and pituitary mitotic and apoptotic responses.

PMID- 15171701
TI  - Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in
      rat osteoblasts.
AB  - In osteoblasts only the type III Na(+)-dependent phosphate (NaPi) transporter
      isoforms Pit-1 and Pit-2 have been identified. We tested the effects of
      extracellular Pi, Ca(2+) and IGF-I on Na(d)Pi transport and Pit-1 or Pit-2 mRNA
      expression in rat osteoblastic (PyMS) cells. The v(max) of Na(d)Pi transport was
      higher in cells kept in Pi-free, serum-free medium for 24 h than in controls at 1
      mM Pi (2.47+/-0.20 vs 1.83+/-0.17 nmol/mg protein x 10 min). The apparent
      affinity constant (K(M)) for Pi remained unchanged. Pi withdrawal for 24 h did
      not impair cell viability whereas increasing the extracellular Pi to 5 mM
      resulted in cell death. Pit-1 (but not Pit-2) mRNA was upregulated following Pi
      deprivation, Ca(2+) treatment or after treatment with 1 nM IGF-I, known to
      stimulate Na(d)Pi transport and cell proliferation. IGF-I also stimulated Na(d)Pi
      transport and Pit-1 mRNA in primary rat calvarial osteoblasts. Expression of Pit
      1 mRNA in vivo and the coordinate regulation of Pit-1 mRNA and Pi transport in
      osteoblastic cells suggest that Pit-1 is a candidate transporter of physiological
      relevance in bone.

PMID- 15171703
TI  - Ubiquitinated or sumoylated retinoic acid receptor alpha determines its
      characteristic and interacting model with retinoid X receptor alpha in gastric
      and breast cancer cells.
AB  - Retinoic acid receptor alpha (RARalpha) plays an important role in mediating all
      trans retinoic acid (ATRA) signals. In this study, we found that ATRA up
      regulated RARalpha mRNA and protein expression in gastric cancer BGC-823 cells.
      However, in breast cancer MCF-7 cells it down-regulated RARalpha protein
      expression with no effect on its RARalpha mRNA. Immunoprecipitation/Western blot
      analysis showed that, although sumoylated and ubiquitinated RARalpha existed
      simultaneously in both cancer cell lines, ATRA exerted different regulatory
      effects on sumoylation and ubiquitination of RARalpha. In MCF-7 cells, ATRA
      treatment enhanced the ubiquitination of RARalpha and the subsequent degradation
      of RARalpha through the ubiquitin/proteasome pathway. This resulted in a
      reduction in the DNA binding activity of RARalpha/retinoid X receptor alpha
      (RXRalpha) heterodimer, the separation of RXRalpha from RARalpha and the
      translocation of RXRalpha from the nucleus to the cytoplasm. By contrast, in BGC
      823 cells, ATRA augmented sumoylation, not ubiquitination, of RARalpha. The
      stability of sumoylated RARalpha was significantly stronger than in non
      sumoylated RARalpha. These results also showed an increase in the DNA binding
      activity of the RARalpha/RXRalpha heterodimer and the stability of nuclear
      localization of this heterodimer, which normally facilitates the ATRA signal
      transduction. In conclusion, our results reveal a novel mechanism for the
      regulation of RARalpha-dependent signal transduction through the
      ubiquitin/proteasome pathway in breast cancer cells and the sumoylation pathway
      in gastric cancer cells.

PMID- 15171702
TI  - Corticotropin-releasing hormone stimulates NF-kappaB in human epidermal
      keratinocytes.
AB  - Corticotropin-releasing hormone (CRH) has been shown to inhibit proliferation and
      modulate expression of inflammation markers in the epidermal cells. In the
      present study we report that CRH also stimulates nuclear factor-kappa B (NF
      kappaB) activity. Incubation with CRH of human keratinocytes derived from primary
      cultures resulted in increased binding of DNA by NF-kappaB. CRH induced
      translocation of NF-kappaB subunit p65 from the cytoplasm to the nucleus and
      induced expression of kappaB-driven chloramphenicol acetyltransferase (CAT)
      reporter gene. NF-kappaB translocation was accompanied by degradation of the
      inhibitor of NF-kappaB alpha (IkappaB-alpha). Specificity of the CRH effect was
      demonstrated by the use of CRH-R antagonists antalarmin and alpha-helical CRH [9
      41]. CRH-dependent stimulation of NF-kappaB activity is consistent with
      accumulated data about role of this neuropeptide in the regulation of local
      epidermal homeostasis.

PMID- 15171704
TI  - Role of foxj1 and estrogen receptor alpha in ciliated epithelial cell
      differentiation of the neonatal oviduct.
AB  - Estrogen regulates proliferation and differentiation of epithelial cells in the
      mammalian oviduct, but pathways for cell-specific differentiation are not well
      understood. In the epithelial cells of the developing rat oviduct, we found
      estrogen receptor (ER) alpha is expressed at birth and persists in all cells
      through neonatal day (ND) 7 when ciliated cells appear. To determine a specific
      function of ER and foxj1, a transcription factor known to have fundamental roles
      in ciliogenesis in the lung, in differentiation of the ciliated epithelial cells,
      we treated newborn rats from ND 0 to 5 with estradiol-17beta (E2) with and
      without a selective ER antagonist. E2 enhanced the number of proliferating cells
      and accelerated the process of epithelial cell differentiation resulting in
      ciliogenesis by ND 5, and co-treatment with an ER antagonist inhibited these
      changes. Foxj1 was expressed only in the infundibulum and ampulla (INF/AMP). That
      expression preceded the appearance of cilia and was induced by E2. Cilia were
      absent in oviducts of foxj1-deficient mice, indicating that foxj1 plays a
      critical role in oviductal ciliogenesis. However, we found the presence of cilia
      in the ERalpha-deficient mouse oviduct. The widespread expression of ERalpha in
      oviductal epithelium, but restriction of cilia to the INF/AMP regions, and
      importantly, the presence of cilia in the ERalpha-deficient mice, suggested ER
      signaling is not essential for ciliated epithelial cell differentiation. These
      observations demonstrate that, although E2 stimulates the differentiation process
      of ciliated epithelial cells, foxj1 is directly required for epithelial cell
      ciliogenesis of the neonatal oviduct.

PMID- 15171705
TI  - Structural characterisation of a cyprinid (Cyprinus carpio L.) CRH, CRH-BP and
      CRH-R1, and the role of these proteins in the acute stress response.
AB  - We elucidated the structure of the principle factors regulating the initiation of
      the acute stress response in common carp: corticotrophin-releasing hormone (CRH),
      CRH-receptor 1 (CRH-R1) and CRH-binding protein (CRH-BP). Phylogenetic analyses
      reveal that these proteins are evolutionarily well conserved in vertebrates. CRH
      and CRH-BP expression are not co-localised in the same hypothalamic perikarya. On
      the contrary, CRH-BP expression is limited to the perimeter of the nucleus
      preopticus (NPO), but is abundant in other regions, including an area directly
      rostral from, and in close proximity to, the NPO. Despite the lack of co
      expression, the nerve fibres projecting onto both the rostral pars distalis (rPD)
      as well as the large fibre bundles projecting onto the pars intermedia (PI)
      contain CRH as well as CRH-BP, suggesting that both ACTH release from the rPD as
      well as the release of PI melanotrope content is regulated via CRH and CRH-BP.
      Finally, we show via real-time quantitative PCR that expression of hypothalamic
      CRH and CRH-BP following a 24 h restraint significantly increases, whereas PD CRH
      R1 expression decreases; this reflects desensitisation of the PD for hypothalamic
      CRH output. We conclude that these factors are actively involved in the
      regulation of acute stress responses in the teleost fish.

PMID- 15171706
TI  - Transcription factor EGR3 is involved in the estrogen-signaling pathway in breast
      cancer cells.
AB  - Estrogen has been closely associated with the genesis and malignant progression
      of breast cancer. However, the molecular mechanism underlying the effects of
      estrogen is far from being completely clarified. We previously developed a custom
      made cDNA microarray consisting of approximately 200 estrogen-responsive genes in
      breast cancer cells. Using this system, we found one estrogen-induced gene in
      various cancer cell lines, including breast cancer MCF-7 cells, which encode a
      zinc-finger transcription factor, EGR3 (early growth response 3). Northern blot
      analysis of estradiol-treated MCF-7 cells showed rapid and robust induction of
      Egr3, and addition of cycloheximide or ICI 182,780 suggested that Egr3 is the
      bona fide target for the estrogen receptor alpha (ERalpha). Using stable
      transformants derived from MCF-7 cells which were transfected with expression
      controllable Egr3-expression vector, we demonstrated that Nab2 is one of the
      target genes for EGR3. Microarray analysis of the transformants revealed other
      candidate EGR3-induced genes. These strategies could be useful for analyzing
      downstream genes of ERalpha, and may contribute to elucidating the extensive
      signaling network of estrogen stimuli. Furthermore, a reporter assay using the
      upstream region of fasL probably involving escape from the immune system revealed
      that fasL is another target gene for EGR3. The roles of EGR3 in the physiology of
      breast cancer are discussed.

PMID- 15171707
TI  - Persistent gene expression in mouse vagina exposed neonatally to
      diethylstilbestrol.
AB  - Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces
      carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment
      induces persistent proliferation and keratinization of the vaginal epithelium,
      even in the absence of the ovaries, resulting in cancerous lesions later in life.
      To understand the mechanisms underlying this persistent cell proliferation and
      differentiation, we characterized the gene expression patterns in the neonatally
      DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR.
      We found that genes related to cellular signaling, which are candidates for
      mediating the persistent proliferation and differentiation, were altered, and
      genes related to the immune system were decreased in the neonatally DES-exposed
      mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes
      accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its
      binding proteins was modulated and led to phosphorylation of IGF-I receptor and
      Akt, which is one of the downstream factors of IGF-I signaling. This led us to
      characterize the expression as well as the phosphorylation status of IL-1 and IGF
      I signaling pathway components which may activate the phosphorylation cascade in
      the vagina of mice exposed neonatally to DES. These findings give insight into
      persistent activation in the vagina of mice exposed neonatally to DES.

PMID- 15171708
TI  - A new mutation of the androgen receptor, P817A, causing partial androgen
      insensitivity syndrome: in vitro and structural analysis.
AB  - Androgen insensitivity syndrome (AIS) is an X-linked disease caused by mutations
      in the androgen receptor (AR) resulting in various degrees of defective
      masculinization in 46,XY individuals. In the present study, we describe a novel
      mutation in exon 7 of the AR gene in an Egyptian patient with partial AIS (PAIS).
      Sequencing analysis of the AR gene revealed a novel missense mutation, P817A,
      within the ligand-binding domain (LBD). This is the first report of a mutation
      within the short amino acid motif (codons 815-817) of the beta-strand lying
      between helices H8 and H9 of the AR LBD. The functional defects of the mutated
      protein were characterized by in vitro study and included significantly decreased
      ligand-binding affinity and impaired transactivation potential. Limited
      proteolysis assays performed with the wild-type and mutant AR receptors incubated
      with the synthetic agonist R1881 revealed that the P817A mutation resulted in a
      reduced stabilization of the AR active conformation. Structural analyses showed
      that this mutation is likely to perturb the beta-sheet interaction between
      residues 815-817 and 911-913. This structural alteration destabilizes the
      position of the C-terminal extension, which contains residues critical for
      androgen function.

PMID- 15171709
TI  - Tissue- and time-dependent estrogen receptor activation in estrogen reporter
      mice.
AB  - With the aim of developing an in vivo model that directly detects activation of
      estrogen receptors (ERs), transgenic mice carrying a luciferase reporter gene
      were generated. The luciferase reporter gene was under the control of three
      consensus estrogen-responsive elements (EREs) coupled to a minimal TATA-box, with
      or without flanking chick beta-globin insulators. By using this model in
      combination with the IVIS imaging system, in vivo ER activation was measured.
      Dose- and time-dependent luciferase activity was induced in various organs of
      adult transgenic male mice exposed to diethylstilbestrol (DES) (10-1000 micro
      g/kg) and 17beta-estradiol dipropionate (EP) (10-1000 micro g/kg), when
      luciferase activity was measured ex vivo. The highest (>10 000-fold) induction of
      luciferase was measured in bone and kidney 24 h after exposure to 1000 micro g/kg
      EP. Other highly responsive organs include liver, testis, pituitary, brain,
      prostate and colon, which show different activity profiles. This in vivo model
      for detecting estrogenic activity can be used to assess tissue-specific action of
      ER agonists and antagonists. These could include selective ER modulators and
      environmental estrogens. In combination with the IVIS imaging system, this in
      vivo model is a powerful tool for assessing the kinetics of gene activation by
      estrogenic compounds.

PMID- 15171710
TI  - Cloning of oestrogen receptor beta from Old and New World primates:
      identification of splice variants and functional analysis.
AB  - Oestrogens have a major impact on reproductive function in both males and
      females. Two oestrogen receptor genes known as ERalpha (ESR1NR3A1) and ERbeta
      (ESR2NR3A2) have been cloned. Splice variant isoforms of the ERbeta gene have
      been identified in human, bovine and rodents and it has been suggested that the
      existence of these forms can influence oestrogen responsiveness. In the human,
      splicing of an alternative eighth exon results in the formation of a C-terminal
      variant called hERbetacx, or hERbeta2, but this isoform has not been identified
      in other species. The aim of the present study was to clone ERbeta cDNAs from
      primates so as to determine how closely they resembled the ERbeta isoforms found
      in the human. The two species studied were the stump-tailed macaque (Macaca
      arctoides), an Old World primate, and the common marmoset (Callithrix jacchus
      jacchus), a New World primate. Full length ERbeta (wild type, ERbeta1) cDNAs were
      cloned from macaque and marmoset; they encoded proteins of similar size to those
      found in human (59 and 54 kDa, long and short forms respectively) and shared
      significant sequence homology (97.5% in macaque and 93.8% in marmoset) with the
      human peptide sequence. Full length cDNAs homologous to the hERbeta2 variant were
      identified in both primates. Marmoset ERbeta2 was slightly shorter than that of
      human ERbeta2 (54 kDa compared with 55 kDa) and did not contain the peptide
      sequence used to raise an anti-hERbeta2 antibody. All the macaque ERbeta2 cDNAs
      contained 56 bp of intronic sequence which included an in-frame stop codon
      resulting in translation of a truncated protein ( approximately 35 kDa). In all
      three species, truncated, alternatively spliced mRNAs lacking exon 5 were
      isolated on multiple occasions from all tissue extracts. In transient
      transfection assays, ERbeta2-containing constructs were unable to induce
      transcription of an oestrogen response element (ERE) reporter plasmid in the
      presence of oestradiol. ERbeta1 from human, macaque and marmoset exhibited minor
      differences in their ability to induce transcription of the ERE reporter when
      incubated with different ligands (oestradiol, PPT, DPN, 5-alpha-androstane-3
      beta, 17beta-diol (3betaAdiol), genistein) and this may be due to amino acid
      substitutions within their ligand binding domains. In conclusion, we have
      identified and cloned wild type ERbeta (ERbeta1) from macaque and marmoset and
      demonstrated that splice variant mRNAs homologous to hERbeta2 are formed in both
      species. The marmoset monkey, therefore, provides a suitable animal model in
      which to investigate the impact of ERbeta variant expression on tissue
      responsiveness to oestrogens.

PMID- 15171711
TI  - A genomic view of estrogen actions in human breast cancer cells by expression
      profiling of the hormone-responsive transcriptome.
AB  - Estrogen controls key cellular functions of responsive cells including the
      ability to survive, replicate, communicate and adapt to the extracellular milieu.
      Changes in the expression of 8400 genes were monitored here by cDNA microarray
      analysis during the first 32 h of human breast cancer (BC) ZR-75.1 cell
      stimulation with a mitogenic dose of 17beta-estradiol, a timing which corresponds
      to completion of a full mitotic cycle in hormone-stimulated cells. Hierarchical
      clustering of 344 genes whose expression either increases or decreases
      significantly in response to estrogen reveals that the gene expression program
      activated by the hormone in these cells shows 8 main patterns of gene
      activation/inhibition. This newly identified estrogen-responsive transcriptome
      represents more than a simple cell cycle response, as only a few affected genes
      belong to the transcriptional program of the cell division cycle of eukaryotes,
      or showed a similar expression profile in other mitogen-stimulated human cells.
      Indeed, based on the functions assigned to the products of the genes they
      control, estrogen appears to affect several key features of BC cells, including
      their metabolic status, proliferation, survival, differentiation and resistance
      to stress and chemotherapy, as well as RNA and protein synthesis, maturation and
      turn-over rates. Interestingly, the estrogen-responsive transcriptome does not
      appear randomly interspersed in the genome. In chromosome 17, for example, a site
      particularly rich in genes activated by the hormone, physical association of co
      regulated genes in clusters is evident in several instances, suggesting the
      likely existence of estrogen-responsive domains in the human genome.

PMID- 15171712
TI  - Oestrogen receptor beta is required for androgen-stimulated proliferation of
      LNCaP prostate cancer cells.
AB  - The role of oestrogens in the development of prostate cancer is poorly
      understood. However, a large body of evidence has suggested that oestrogenic
      hormones may be involved in prostatic malignancy. The localization of oestrogen
      receptor beta (ERbeta) in the secretory epithelium of the human prostate has
      raised the intriguing possibility that the action of oestrogen could be mediated,
      at least in part, by this receptor during the process of carcinogenesis. Hence,
      specific interference with oestrogen-activated and ERbeta-mediated
      transcriptional activity could open new issues in the endocrine manipulation of
      prostate tumours. In the present study, we provide new insights into the role of
      ERbeta in the context of an androgen-responsive prostate cancer cell line such as
      LNCaP, which was used as a model system together with steroid receptor negative
      HeLa cells. ERbeta and the mutated androgen receptor (AR) T877A did not
      discriminate between oestrogen- or androgen-induced transactivation, whereas
      ERbeta and AR transcriptional activity were inhibited only by the respective
      hormone antagonists ICI 182,780 and casodex. Furthermore, the nuclear
      localization of ERbeta evaluated by immunocytochemistry confirmed the promiscuous
      response to hormones in addition to the specific inhibitory action of
      antagonists. Interestingly, ICI 182,780 and an ERbeta antisense expression vector
      repressed the growth effects of both 17beta-oestradiol and 5alpha
      dihydrotestosterone, suggesting that ERbeta has a key role in the proliferation
      induced by these steroids in LNCaP prostate cancer cells. Thus our findings
      implicate ERbeta as a potential target for the treatment of prostate tumours.

PMID- 15171713
TI  - Inhibition of MCF-7 breast cancer cell proliferation by 5alpha
      dihydrotestosterone; a role for p21(Cip1/Waf1).
AB  - Androgens inhibit the growth of breast cancer cells in vitro and in vivo by
      mechanisms that remain poorly defined. In this study, treatment of asynchronously
      growing MCF-7 breast cancer cells with the androgen, 5alpha-dihydrotestosterone
      (DHT), was shown to inhibit cell proliferation and induce moderate increases in
      the proportion of G1 phase cells. Consistent with targeting the G1-S phase
      transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced
      progression of G1-arrested cells into S phase and reduced the kinase activities
      of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3
      days. DHT treatment was associated with greater than twofold increases in the
      levels of the Cdk inhibitor, p27(Kip1), while p21(Cip1/Waf1) protein levels
      remained unchanged. During the first 24 h of DHT treatment, levels of Cdk4
      associated p21(Cip1/Waf1) and p27(Kip1) were reduced coinciding with decreased
      levels of Cdk4-associated cyclin D3. In contrast, DHT treatment caused increased
      accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations
      in levels of p27(Kip1) bound to Cdk2 complexes. These findings suggest that DHT
      reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from
      Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2
      complexes in part mediates the androgen-induced growth inhibition of breast
      cancer cells.

PMID- 15171715
TI  - The manifold actions of the protein inhibitor of activated STAT proteins on the
      transcriptional activity of mineralocorticoid and glucocorticoid receptors in
      neural cells.
AB  - Corticosteroid actions in the brain are exerted via the mineralocorticoid
      receptor (MR) and glucocorticoid receptor (GR). These receptors share several
      structural and functional similarities but their activation in the brain triggers
      distinct biological actions, for instance on neuronal survival or the regulation
      of the hypothalamo-pituitary-adrenal axis. Like other hormone-activated
      receptors, the transcriptional properties of the MR and GR depend on their
      ability to recruit a variety of co-regulators, which modulate their activity on
      target promoters, in a specific manner. The N-terminal regions of the MR and GR
      share the smallest degree of sequence conservation, whereas they display opposite
      effects on the transactivation properties of these receptors; thus, they may
      provide surfaces suitable for receptorspecific interactions with co-regulatory
      proteins. Here, we employed a yeast two-hybrid system to identify molecules
      interacting with the N-terminal part of the MR (amino acids 170-433). This
      approach resulted in the isolation of representative cDNAs from all members of
      the protein inhibitor of activated STAT (PIAS) family of proteins as potential MR
      interacting partners. In neural cells, PIAS3 exhibited a strong and specific
      interaction with MR, but not GR, as indicated by mammalian two-hybrid assays and
      co-immunoprecipitation experiments in vivo. The interaction with MR was enhanced
      in the presence of aldosterone, an MR agonist, and was found to occur through a
      conserved, serine- and acidic amino acid residue-rich domain of PIAS3. To compare
      the modulatory properties of PIAS proteins on MR and GR transcriptional activity
      in a neural environment, MMTV reporter gene assays were performed in the human
      neuroblastoma cell line SK-N-MC. This analysis revealed that PIAS3 can inhibit
      MR, but not GR, transactivation in response to their corresponding ligands.
      Further, it showed that PIAS1 and PIASxbeta, but not PIASy, could also inhibit MR
      mediated transcription despite the lack of detected physical interaction with MR.
      Interestingly, PIASxbeta and PIASy dose-dependently co-activated GR, whereas
      PIAS1 impaired GR-induced transcription. Taken together the results reveal
      differential modulatory roles of the PIAS proteins on the transcriptional
      properties of MR and GR, thus providing new insights into the bifurcating actions
      of these two receptors in neural cells where they are frequently co-localized.

PMID- 15171714
TI  - An E-box-containing region is involved in the tissue-specific expression of the
      human MC2R gene.
AB  - Expression of the melanocortin receptor (MC2R) gene is limited to adrenocortical
      cells and the aim of this study was to determine the factors responsible for this
      tissue specificity. We used different fragments of the human (h) MC2R gene
      promoter, inserted in a vector upstream of the luciferase reporter gene, to
      transiently transfect either bovine adrenocortical (BAC) cells or granulosa cells
      from bovine ovaries (B-Gran). Similar promoter activities were obtained in both
      cell types using constructs containing fragments up to 1017 bp of the hMC2R gene
      promoter. On the contrary, a 2-fold decrease was obtained after transfection of
      the B-Gran cells with vectors containing 1069 bp and more of the promoter.
      Results obtained here using BAC cells confirmed our previous data on human cells
      showing that steroidogenic factor 1 is the major transactivating factor involved
      in the basal expression of the hMC2R gene in adrenal cells. However, we showed
      that this factor did not permit, by itself, the expression of the hMC2R gene in B
      Gran cells despite its expression in these cells. This study demonstrated for the
      first time that an E-box (located at -1020 bp) is involved in the repression of
      hMC2R gene expression in granulosa cells through interactions with several
      factors, such as activator protein 4, as suggested by electrophoretic mobility
      shift assay analyses.

PMID- 15171716
TI  - Intramolecular interactions between the AF3 domain and the C-terminus of the
      human progesterone receptor are mediated through two LXXLL motifs.
AB  - The human progesterone receptor (PR) exists in two major forms, PRA and PRB,
      which differentially regulate gene transcription in a cell- and promoter-specific
      manner. The molecular mechanisms underlying this differential transcriptional
      activity have been attributed to the presence of a unique AF3 domain within PRB
      that may result in the two isoforms adopting different protein conformations. We
      demonstrate here that in myometrial cells, PRB exhibits strong progesterone
      dependent transcriptional activity that is dependent on the presence of two LXXLL
      motifs within the AF3 domain. In vitro and in vivo protein interaction assays
      indicate that these motifs mediate the direct interaction between the AF3 domain
      and C-PR in a progesterone-dependent manner. Mutation of either of the LXXLL
      motifs or deletion of the last 30 amino acids within the C-terminus disrupts this
      interaction and progesterone-dependent transcriptional activity of PRB. Members
      of the p160 family of co-activators (such as GRIP-1) also interact with C-PR
      through their LXXLL motifs. However, GRIP-1 does not compete with AF3 but rather
      acts to synergize these two transactivation domains. Our data suggest that a
      failure to form an appropriate AF3-C-terminus interaction results in an inability
      of co-activators to induce maximal PR-dependent transactivation. The absence of
      an AF3 domain within PRA may account for its inability to activate progesterone
      responsive genes, as well as its actions as a dominant trans-repressor.

PMID- 15171717
TI  - Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor
      cells.
AB  - The neoplastic production of the insulin-like growth factor binding protein
      (IGFBP)-2 often correlates with tumor malignancy and aggressiveness. Since IGFBP
      2 contains an RGD motif in its C-terminus, it was hypothesized that this protein
      may act independently of IGF on tumor cells through integrins. To investigate
      this, integrin binding, intracellular signaling and the impact of IGFBP-2 on cell
      adhesion and proliferation were examined in two tumor cell lines. In tracer
      displacement studies, up to 30% of the added (125)I-hIGFBP-2 specifically bound
      to the cells. Bound (125)I-hIGFBP-2 was reversibly displaced by IGFBP-2, IGFBP-1
      and RGD-(Gly-Arg-Asp)-containing peptides, but not by IGFBP-3, -4, -5, -6 and RGE
      (Gly-Arg-Glu)-containing peptides. Blocking with antibodies directed against
      different integrins and with fibronectin demonstrated that IGFBP-2 cell surface
      binding is specific for alpha5beta1-integrin. Incubation of IGFBP-2 with
      equimolar quantities of IGF-I and IGF-II annihilated RGD-specific binding. IGFBP
      2 binding at the cell surface led to dephosphorylation of the focal adhesion
      kinase (FAK) of up to 37% (P<0.01), and of the p42/44 MAP-kinases of up to 40%
      (P<0.01). In addition, IGFBP-2 promoted de-adhesion of the cells dose-dependently
      by up to 30% (P<0.05), and reduced proliferation by 24% (P<0.01). Since one of
      the cell lines used does not express a functional IGF-I receptor, these data
      demonstrate that IGFBP-2 can act in an IGF-independent manner, at least in part
      by an interaction with alpha5beta1-integrin.

PMID- 15171718
TI  - Vasoactive intestinal peptide (VIP) stimulates cortisol secretion from the H295
      human adrenocortical tumour cell line via VPAC1 receptors.
AB  - Vasoactive intestinal peptide (VIP) shows a wide tissue distribution and exerts
      numerous physiological actions. VIP was shown in a dose-dependent manner to
      increase cortisol secretion in the NCI-H295R human adrenocortical carcinoma
      (H295) cell line (threshold dose 3.3x10(-10) M, maximal dose 10(-7) M), coupled
      with a parallel increase in cAMP accumulation. Receptor-specific agonists were
      employed to determine which of the two known VIP receptor subtypes was involved
      in cortisol secretion. Treatment with the VPAC1 receptor agonist, [K(15), R(16),
      L(27)]VIP(1-7)/GRF(8-27), produced a dose-dependent increase in H295 cell
      cortisol secretion (threshold dose 10(-11) M, maximal dose 10(-7) M) similar to
      that seen with VIP. Meanwhile, the high-affinity VPAC2 receptor agonist, RO-25
      1553, failed to stimulate significantly cortisol or cAMP production from H295
      cells. Inhibition of VIP-mediated H295 cell cortisol secretion by PG97-269, a
      competitive VPAC1-specific antagonist, produced parallel shifts of the dose
      response curve and a Schild regression slope of 0.99, indicating competitive
      inhibition at a single receptor subtype. VIP is known also to interact with the
      PAC1 receptor, albeit with lower affinity (EC(50) of approximately 200 nM) than
      the homologous ligand, PACAP (EC(50) of approximately 0.5 nM). PACAP stimulated
      cortisol secretion from H295 cells (EC(50) of 0.3 nM), suggesting the presence of
      functional PAC1 receptors. However, stimulation of cortisol secretion by
      nanomolar concentrations of VIP (EC(50) of 5 nM), coupled with real-time PCR
      estimation that VPAC1 receptor transcripts appear 1000-fold more abundant than
      PAC1 transcripts in H295 cells, makes it unlikely that VIP signals via PAC1
      receptors. Together, these data suggest that VIP directly stimulates cortisol
      secretion from H295 cells via activation of the VPAC1 receptor subtype.

PMID- 15171719
TI  - Gene expression profiling identifies liver X receptor alpha as an estrogen
      regulated gene in mouse adipose tissue.
AB  - Estrogens reduce adipose tissue mass in both humans and animals. The molecular
      mechanisms for this effect are, however, not well characterized. We took a gene
      expression profiling approach to study the direct effects of estrogen on mouse
      white adipose tissue (WAT). Female ovariectomized mice were treated for 10, 24
      and 48 h with 17beta-estradiol or vehicle. RNA was extracted from gonadal fat and
      hybridized to Affymetrix MG-U74Av2 arrays. 17beta-Estradiol was shown to decrease
      mRNA expression of liver X receptor (LXR) alpha after 10 h of treatment compared
      with the vehicle control. The expression of several LXRalpha target genes, such
      as sterol regulatory element-binding protein 1c, apolipoprotein E, phospholipid
      transfer protein, ATP-binding cassette A1 and ATP-binding cassette G1, was
      similarly decreased. We furthermore identified a 1.5 kb LXRalpha promoter
      fragment that is negatively regulated by estrogen. Several genes involved in
      lipogenesis and lipolysis were identified as novel targets that could mediate
      estrogenic effects on adipose tissue. Finally, we show that ERalpha is the main
      estrogen receptor expressed in mouse white adipose tissue (WAT) with mRNA levels
      several hundred times higher than those of ERbeta mRNA.

PMID- 15171720
TI  - Reciprocal influences between the signalling pathways regulating proliferation
      and steroidogenesis in adrenal glomerulosa cells.
AB  - The main regulators of aldosterone secretion in adrenal gland zona glomerulosa
      (ZG) cells are the hormones angiotensin II (Ang II) and adrenocorticotrophin
      (ACTH) and small increases in the extracellular potassium (K(+)) concentration.
      The action of these agonists is mediated by different signalling systems - ACTH
      is mediated by cAMP and activation of protein kinase A while Ang II and K(+)
      activate two protein kinases, Ca(2+)-calmodulin-dependent protein kinase (CamK)
      and diacylglycerol-dependent protein kinase (PKC). Ang II, besides being one of
      the main agonists for the secretion of aldosterone, also stimulates proliferation
      of ZG cells, a process mediated by mitogen-activated protein kinases (MAPKs).
      Recent studies aimed at elucidating the molecular mechanisms underlying cell
      proliferation have shown that calcineurin is the principal regulator of MAPKs
      activity. The purpose of this review is to discuss experimental evidence of
      possible reciprocal influences between the signalling pathways regulating
      proliferation and steroidogenesis in ZG cells.

PMID- 15171722
TI  - Acute neurosteroid modulation and subunit isolation of the gamma-aminobutyric
      acidA receptor in the bullfrog, Rana catesbeiana.
AB  - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has multiple
      receptors. In mammals, the GABA(A) receptor subtype is modulated by
      neurosteroids. However, whether steroid interaction with the GABA(A) receptor is
      unique to mammals or a conserved feature in vertebrates is unknown. Thus,
      neurosteroid modulation of the GABA(A) receptor was investigated in the brain of
      the bullfrog (Rana catesbeiana) using the mammalian GABA(A) receptor agonist
      [(3)H]muscimol. Two neurosteroids, allopregnanolone and pregnenolone sulfate,
      affected [(3)H]muscimol specific binding in bullfrog brain membrane preparations.
      Allopregnanolone significantly increased [(3)H]muscimol specific binding in a
      dose- and time-dependent manner. The pattern of allopregnanolone modulation
      supports the hypothesis that the bullfrog brain possesses both high-affinity and
      low-affinity [(3)H]muscimol binding sites. Unlike allopregnanolone, pregnenolone
      sulfate showed biphasic modulation with increased [(3)H]muscimol specific binding
      at low nanomolar concentrations and decreased specific binding at micromolar
      concentrations. Additionally, three cDNA fragments with significant homology to
      mammalian GABA(A) receptor subunits were isolated from the bullfrog brain. These
      fragments belong to the alpha1, beta1, and gamma2 subunit families. In mammals,
      GABA(A) receptors composed of these specific subunit isoforms are effectively
      modulated by neurosteroids, including allopregnanolone. Neurosteroid modulation
      of the amphibian brain GABA(A) receptor is therefore supported by both
      [(3)H]muscimol binding studies and subunit sequences. Allopregnanolone and
      pregnenolone sulfate modulation of this receptor may thus represent a significant
      mechanism for steroid influence on amphibian brain and behavior.

PMID- 15171721
TI  - Unfolded protein response is involved in the pathology of human congenital
      hypothyroid goiter and rat non-goitrous congenital hypothyroidism.
AB  - The unfolded protein response (UPR) is an intracellular signaling pathway that
      regulates the protein folding and processing capacity of the endoplasmic
      reticulum (ER). The UPR is induced by the pharmacological agents that perturb ER
      functions but is also activated upon excessive accumulation of the mutant
      secretory proteins that are unable to attain correct three-dimensional structure
      and are thus retained in the ER. Such defects in intracellular protein transport
      underlie the development of a number of phenotypically diverse inherited
      pathologies, termed endoplasmic reticulum storage diseases (ERSD). We have
      studied UPR development in two similar ERSDs, human congenital goiter caused by
      the C1264R and C1996S mutations in the thyroglobulin (Tg) gene and non-goitrous
      congenital hypothyroidism in rdw dwarf rats determined by the G2320R Tg mutation.
      In both cases, these mutations rendered Tg incapable of leaving the ER. A major
      ER chaperone immunoglobulin-binding protein (BiP), and a novel putative escort
      chaperone endoplasmic reticulum protein 29 KDa (ERp29) were found to be
      associated with Tg, which might be interpreted as the contribution of the quality
      control machinery to the previously shown retention of Tg in the ER. We have
      extended our earlier observations of ER chaperone induction with the
      identification of the additional ER (ERp29, ERp72, calreticulin, protein
      disulfide isomerase (PDI)), cytoplasmic (heat shock protein (HSP)70, HSP90) and
      mitochondrial (mtHSP70) upregulated chaperones and folding enzymes. Activation of
      the transcriptional arm of UPR, as judged by the appearance of the spliced
      (active) form of X-box binding protein (XBP1) and processed activating
      transcription factor 6 (ATF6) transcription factors was suggested to contribute
      to the overexpression of the ER chaperones. The processing of ATF6 was observed
      in both human and rat tissues with Tg mutations. Whereas, in human tissues, weak
      splicing of XBP1 mRNA was detected only in the C1264R mutant, all rat thyroids
      including wild-type contained significant amounts of the spliced form of XBP1 as
      opposed to human liver and rat brain tissues, implying the existence of a
      previously unknown tissue-specific regulation of XBP1 processing.

PMID- 15171723
TI  - Expression of an estrogen receptor variant lacking exon 3 in derivatives of MCF-7
      cells with acquired estrogen independence or tamoxifen resistance.
AB  - The estrogen receptor (ER) plays important roles in the development and
      progression of breast cancer, and is a major target for tumor therapy. In this
      study, we investigated ER function in two derivatives of MCF-7 cells that were
      selected for their ability to proliferate in the absence of estrogen or in the
      presence of the antiestrogen, tamoxifen. Reporter gene assays indicated decreased
      ER activity in both cells lines, although the activity remaining retained
      responsiveness to both estrogen and tamoxifen. The decreased ER activity
      correlated with expression of a 61 kDa variant ER protein, and sequencing of RT
      PCR products indicated that this variant was the product of an exon 3 deletion
      (ERDeltaE3). To study its effects on cell proliferation, ERDeltaE3 cDNA was
      stably transfected into both the MCF-7 cell line and its estrogen
      independent/tamoxifen-sensitive derivative MCF-7/LCC1 (LCC1), and the phenotypes
      of transfectants were examined. Expression of ERDeltaE3 was not sustainable in
      MCF-7 cells, but was maintained for at least 17 passages in LCC1 cells. These
      results are in agreement with previous reports that ERDeltaE3 inhibits wild-type
      ER activity and negatively regulates proliferation of MCF-7 cells. They further
      suggest that the alteration that leads to estrogen independence in LCC1 cells
      allows for sustained expression of ERDeltaE3, and that additional changes are
      required to confer tamoxifen resistance to these cells.

PMID- 15171724
TI  - Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and
      hepatocyte nuclear factor 4gamma (HNF-4gamma) and HNF-4alpha regulate the bovine
      growth hormone receptor 1A promoter through a common DNA element.
AB  - The growth hormone receptor (GHR) 1A promoter is responsible for transcription of
      the liver-specific GHR mRNA variant 1A in several mammalian species. We
      previously found that the region between nucleotide -218 and nucleotide -151
      (relative to the major transcription start site) of the bovine GHR 1A promoter
      contained a binding site between -196 and -178 for the liver-enriched
      transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) and that the
      same region might also interact with additional transcription factors in the
      liver. Using the -218/-151 region as bait to screen a bovine liver cDNA library
      in a yeast one-hybrid analysis, we identified chicken ovalbumin upstream promoter
      transcription factor II (COUP-TFII) and HNF-4gamma, as well as HNF-4alpha, as
      binding proteins to the -218/-151 region. These binding proteins were also
      identified in a second yeast one-hybrid analysis using the -196/-178 region as
      bait, suggesting that COUP-TFII, HNF-4gamma and HNF-4alpha all bind to the -196/
      178 region. Electrophoretic mobility shift assays confirmed the ability of these
      three transcription factors in bovine liver nuclear extracts to interact with the
      -196/-178 region. These interactions also appeared to exist in vivo, as the GHR
      1A promoter containing the -196/-178 region could be recovered by
      immunoprecipitation of the bovine liver chromatin with antibody against COUP
      TFII, HNF-4gamma or HNF-4alpha. In co-transfection analyses, each of these three
      transcription factors could activate GHR 1A promoter and the activation was
      dependent on the -196/-178 region. These results together identify COUP-TFII, HNF
      4gamma and HNF-4alpha as transcription factors regulating GHR 1A promoter
      activity through binding to a common DNA element.

PMID- 15171725
TI  - Identification and tissue distribution of mRNAs encoding salmon-type calcitonins
      IV and -V in the rainbow trout.
AB  - Four types of calcitonin are produced in salmonid fish, although their functional
      diversity is almost unknown. To explore the significance of these isoforms, we
      have characterized salmon-type calcitonin (sCT) mRNAs in the rainbow trout
      (Oncorhynchus mykiss), and examined their tissue distribution. In addition to the
      previously isolated sCT-I cDNAs, two new forms of sCT cDNA were cloned from the
      ultimobranchial gland, and one of them (sCT-IV cDNA) was predicted to encode an N
      terminal peptide of 80 amino acid residues, a putative cleavage site Lys-Arg, sCT
      IV, a cleavage and amidation sequence Gly-Lys-Lys-Arg, and a C-terminal peptide
      of 18 amino acids. The sCT-IV precursor was 78% identical with the rainbow trout
      sCT-I precursors. The other cloned cDNA encoded a precursor for a novel CT, sCT
      V. The sCT-V peptide was different from sCT-IV by only one amino acid residue:
      Val at position 8 in the latter was replaced by Met. The sCT-V precursor had 80
      and 90% identity with the sCT-I and -IV precursors respectively. No cDNA clones
      were obtained for sCTs-II or -III.Tissue distribution of sCT-I, -IV and -V mRNAs
      was examined by RT-PCR and specific cleavage with restriction enzymes. An
      amplified fragment from sCT-I mRNA was detected not only in the ultimobranchial
      gland, but also in the gills, testis and ovary. RT-PCR analysis coupled to
      restriction digestion further revealed that sCT-IV mRNA was expressed in both the
      testis and the ultimobranchial gland. The expression sites of sCT-IV mRNA were
      localized to the Leydig cells of the testis and to the parenchymal cells of the
      ultimobranchial gland, by in situ hybridization histochemistry. Although the
      amino acid sequence of sCT-V peptide was nearly the same as that of sCT-IV, the
      sCT-V gene showed a much wider pattern of expression: the band amplified by RT
      PCR was detected in all the tissues examined except the kidney, gills and blood
      cells. The sCT-V mRNA was shown to be localized in the parenchymal cells of the
      ultimobranchial gland, but not in other tissues at the cellular level, suggesting
      very low expression of sCT-V mRNA in those tissues. Our results show different
      patterns of tissue expression of three types of sCT genes in the rainbow trout,
      suggesting that sCTs-I, -IV and -V might differ in their local actions.

PMID- 15171726
TI  - Analysis of the estrogen regulation of the zebrafish estrogen receptor (ER)
      reveals distinct effects of ERalpha, ERbeta1 and ERbeta2.
AB  - We have previously cloned and characterized three estrogen receptors (ER) in the
      zebrafish (zfERalpha, zfERbeta1 and zfERbeta2). We have also shown that they are
      functional in vitro and exhibit a distinct expression pattern, although partially
      overlapping, in the brain of zebrafish. In this paper, we have shown that the
      hepatic expression of these zfER genes responds differently to estradiol (E2). In
      fact, a 48-h direct exposure of zebrafish to E2 resulted in a strong stimulation
      of zfERalpha gene expression while zfERbeta1 gene expression was markedly reduced
      and zfERbeta2 remained virtually unchanged. To establish the potential
      implication of each zfER in the E2 upregulation of the zfERalpha gene, the
      promoter region of this gene was isolated and characterized. Transfection
      experiments with promoter-luciferase reporter constructs together with different
      zfER expression vectors were carried out in different cell contexts. The data
      showed that in vivo E2 upregulation of the zfERalpha gene requires ERalpha itself
      and a conserved transcription unit sequence including at least an imperfect
      estrogen-responsive element (ERE) and an AP-1/ERE half site at the proximal
      transcription initiation site. Interestingly, although in the presence of E2
      zfERalpha was the most potent at inducing the expression of its own gene, the
      effect of E2 mediated by zfERbeta2 represented 50% of the zfERalpha activity. In
      contrast, zfERbeta1 was unable to upregulate the zfERalpha gene whereas this
      receptor form was able to tightly bind E2 and activate a reporter plasmid
      containing a consensus ERE. Altogether, these results indicated that the two
      ERbeta forms recently characterized in teleost fish could have partially distinct
      and not redundant functions.

PMID- 15171727
TI  - Distinct effects of the antiestrogen Faslodex on the stability of estrogen
      receptors-alpha and -beta in the breast cancer cell line MCF-7.
AB  - The effects of estrogen receptor (ER) ligands on the stability and
      transcriptional activity of ERbeta in the breast cancer cell lines MCF-7 and HeLa
      were examined. We found that ERbeta was degraded in the presence of 17beta
      estradiol. Tamoxifen and Faslodex (ICI 182,780) prevented ERbeta receptor
      destabilization. In contrast to ERalpha, ERbeta degradation was not abolished by
      inhibitors of the proteasome-mediated protein degradation pathway. Furthermore,
      single point mutations in helix 12 of the receptor dramatically affected the
      stability and subsequent transcriptional activation of ERbeta.

PMID- 15171728
TI  - Platelet cell-surface protein disulphide-isomerase mediated S-nitrosoglutathione
      consumption.
AB  - S-nitrosothiols (RSNOs) regulate several aspects of platelet physiology including
      inhibition of activation, adhesion and aggregation. PDI (protein disulphide
      isomerase) has recently been found to be localized to the cell surface, where it
      exhibits both disulphide-exchange and denitrosation activities. The disulphide
      exchange activity of PDI has been linked to aspects of platelet aggregation. The
      present study suggests that the metabolism of RSNOs by platelets is a function of
      PDI denitrosation activity. Exposure of washed human platelets to increasing
      concentrations of GSNO (S-nitrosoglutathione) resulted in saturable denitrosation
      kinetics. The presence of known PDI inhibitors phenylarsine oxide and anti-PDI
      antibodies prevented GSNO denitrosation. The fact that, in the presence of GSNO
      plus the cell-permeable guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3
      a]quinoxaline-1-one, the initial rates of ADP-induced platelet aggregation and
      the maximum DeltaOD were diminished by approximately 40% shows that RSNOs have
      dual inhibitory effects on platelets, which are mediated through PDI. First, PDI
      denitrosates RSNOs, releasing NO that, via the guanylate cyclase/G-kinase route,
      attenuates platelet activation. Secondly, RSNOs are denitrosated at the same PDI
      active site that catalyses the disulphide bond formation between integrins and
      their ligands, thereby attenuating irreversible aggregation.

PMID- 15171731
TI  - Efficacy of pharmacological treatment of dystonia: evidence-based review
      including meta-analysis of the effect of botulinum toxin and other cure options.
AB  - The treatment of both generalized and focal dystonia is symptomatic. There is no
      evidence-based information about the efficacy of the different methods of the
      pharmacological therapeutic options currently being applied in dystonia. The
      specific questions addressed by this study were which treatments for dystonia
      have proven efficacy and which of them have unproven results. Following evidence
      based principles, a literature review based on MEDLINE and the Cochrane Library,
      augmented by manual search of the most important journals was performed to
      identify the relevant publications issued between 1973 and 2003. All articles
      appearing in the professional English literature, including case reports, were
      considered. In the presence of comparable studies the meta-analysis was performed
      to obtain pooled information and make a reasonable inference. Based on this
      review, we conclude: (i) botulinum toxin has obvious benefit (level A, class I-II
      evidence) for the treatment of cervical dystonia and blepharospasm; (ii)
      trihexyphenidyl in high dosages is effective for the treatment of segmental and
      generalized dystonia in young patients (level A, class I-II evidence); (iii) all
      other methods of pharmacological intervention for generalized or focal dystonia,
      including botulinum toxin injections, have not been confirmed as being effective
      according to accepted evidence-based criteria (level U, class IV studies).

PMID- 15171729
TI  - Mapping of an ankyrin-sensitive, phosphatidylethanolamine/phosphatidylcholine
      mono- and bi-layer binding site in erythroid beta-spectrin.
AB  - It has been shown previously that binding of vesicles and monolayers containing
      PE (phosphatidylethanolamine) by either erythroid or non-erythroid spectrin
      proved sensitive to inhibition by purified erythrocyte ankyrin. We tested the
      lipid-binding affinities of the purified ankyrin-binding domain of beta-spectrin
      and of its truncated mutants in four ways, by analysing: (1) penetration of
      'loose' PE/PC (phosphatidylcholine) monolayers; (2) binding to liposomes in
      suspension; (3) competition with spectrin for liposomes; and (4) binding of a
      PE/PC monolayer in a surface plasmon resonance system. The results obtained
      indicated that the full-length ankyrin-binding domain bound PE/PC mono- and bi
      layers with moderate affinity, penetrated monolayers and competed with spectrin
      for liposomes. Moreover, its truncated mutants that retained the N-terminal part,
      in contrast with those lacking eight or 38 N-terminal residues (which bound lipid
      mono- and bi-layers with lower affinity), bound PE/PC mono- and bi-layers with an
      affinity and capacity comparable with those of the full-length ankyrin-binding
      domain, and this activity was inhibited by purified erythrocyte ankyrin. The full
      length domain, in contrast with the mutant lacking 38 N-terminal residues,
      induced a small increase in the fluidity of PE/PC membranes when probed with 5'
      doxyl stearate, similar to the effect of purified spectrin. Therefore we conclude
      that the binding site for PE-rich lipids, which is sensitive to ankyrin
      inhibition, is located in a 38-residue N-terminal fragment of the beta-spectrin
      ankyrin-binding domain, and that the first eight residues play a key role in this
      activity.

PMID- 15171732
TI  - The enigma of Lenin's (1870-1924) malady.
AB  - The health of heads of states is not always handled in the same way as an
      incapacitating disability in ordinary professionals. Instead of suspension of
      responsibilities, the health status of political leaders is concealed, especially
      when the illness is perceived as stigmatizing, such as organic mental impairment
      or sexual disorder. The objective of the present paper is to analyse the malady
      of Lenin (1870-1924) in the light of relevant and new medical information. It is
      hoped that this will accentuate the need for transparency when the health of a
      statesman is concerned.

PMID- 15171733
TI  - Different cytokine levels in thrombolysis patients as predictors for clinical
      outcome.
AB  - Thrombolytic therapy not always improves clinical outcome in ischemic stroke
      patients. This could cause lymphomonocyte accumulation in the infarcted brain
      area. These produce an excessive amount of proinflammatory cytokines, such as IL
      1 beta, IL-6 and TNF-alfa. The aim of our study was to determine ILs levels in
      fibrinolytic therapy treated patients, compared with healthy controls and to
      evaluate if the varying levels can predictors of neurological outcome. Eighteen
      patients underwent thrombolytic treatment with t-PA within 3 h. Plasma levels of
      IL-1 beta, IL-6, TNF-alfa and IL-10 were determined by ELISA method before and
      within 24 h after t-PA infusion and compared with controls. Significantly higher
      levels of IL-1 beta and Il-6 emerged in stroke patients before treatment compared
      with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma
      levels of TNF-alfa and lower plasma levels of IL-10 were also found at base line
      in stroke patients. After thrombolytic treatment no significant variations were
      observed in the levels of TNF-alfa and IL-6, whereas a trend toward lower values
      for IL-1 beta and higher levels for IL-10 was observed. Positive correlations
      among the values of IL-6, TNF-alfa and National Institute of Health Stroke Scale
      (NIHSS) at discharges were observed. A similar correlation with modified Rankin
      scale score at 3 month was found. Pre-treatment cytokine status seems to
      influence pre-and long-term clinical outcome. Therefore an investigation into the
      possible predictor of cytokines seem worthy.

PMID- 15171734
TI  - Guillain-Barre syndrome in Greece: seasonality and other clinico-epidemiological
      features.
AB  - The epidemiologic and clinical features of Guillain-Barre syndrome (GBS) during a
      13-year period in a region of south-western Greece with an average population of
      819 009 inhabitants are described. Clinical records of all patients between 1
      January 1989 and 31 December 2001 who were admitted in the two referring
      hospitals of the above district and fulfilled the criteria for idiopathic GBS
      were reviewed. Overall 105 patients were identified. The age adjusted to European
      population incidence rate per 100 000 person-years was 1.02 (95% CI: 0.84-1.24)
      and a male preponderance was found. The highest number of cases (35; 33.3%)
      occurred in spring and the lowest (17; 16.2%) in autumn, although this tendency
      did not reach a significant level. Cases with and without preceding illness were
      similarly distributed in the seasons. Electrophysiologic abnormalities of axonal
      type were found in 6.1% of patients. The mortality rate was 2.8% and the long
      term outcome 5%. The incidence of GBS was relatively low and the prognosis was
      close to the best reported. Spring clustering has also been observed in other
      countries with mild climate.

PMID- 15171735
TI  - Primary headaches in an outpatient neurology headache clinic in East Hungary.
AB  - The majority of patients with primary headache do not seek medical help. In the
      present study we analyse the characteristics of those patients with primary
      headaches who consulted a single headache outpatient service in East Hungary. All
      consecutive patients with primary headaches referred to the headache center
      between February 2002 and April 2003 were asked to fill in a questionnaire on
      headache characteristics and the migraine disability score (MIDAS) form. A total
      of 327 patients had some form of primary headache: 42% migraine, 31% tension-type
      headache, 1% cluster headache and 26% had combination headache. Of the patients
      95% were younger than 60 years of age. Only 16% of the patients were male.
      Chronic daily headache was found in 41% of patients. Although headache was the
      least severe in tension-type headache, reported disability occurred on much more
      days in this group than in migraine patients. The majority of patients with
      primary headache were in the active age group. Patients with tension-type
      headache need more attention, as disability is more severe in this patient group
      than generally assumed. More attention to the headaches of men and the elderly
      could improve the quality of life in these groups of the Hungarian population.

PMID- 15171736
TI  - Reduced reactivation rate in mutant CuZnSOD and progression rate of amyotrophic
      lateral sclerosis.
AB  - Mutations in the SOD1 gene are associated with familial amyotrophic lateral
      sclerosis (fALS). The mechanisms by which these mutations lead to anterior horn
      cell loss are unknown, however, increased binding of Hsps on the demetallated
      mutant SOD1 has been described which would make the HSPs unavailable for other
      purposes, and reduce the SOD1 concentration in mitochondria, thereby creating a
      proapoptotic situation finally leading to motor neuron death. Here we report the
      recombinant expression of four human copper/zinc superoxide dismutase (CuZnSOD)
      variants, including the wild-type enzyme and mutant proteins associated with
      familial ALS. The bacterial expression level of soluble mutated proteins was
      influenced by the mutations leading to drastically reduced levels of soluble
      CuZnSOD. Simultaneously, increasing levels of insoluble and probably aggregated
      mutated CuZnSOD were identified in bacterial cell pellets. In addition, altered
      reactivation kinetics of the purified mutant apoproteins after expression in
      bacterial culture was shown. Biophysical and biochemical analysis showed that
      zinc incorporation is severely reduced in the CuZnSOD proteins associated with
      the most severely forms of fALS (A4V, G93A). These data indicate that a reduced
      holoenzyme formation rate of mutant enzymes may be a critical factor in the
      etiopathology of fALS.

PMID- 15171737
TI  - Hyperhomocysteinemia and other thrombophilic risk factors in 26 patients with
      cerebral venous thrombosis.
AB  - Despite the continuous description of new conditions pre-disposing for cerebral
      venous thrombosis (CVT), no apparent cause is found in about 30% of cases.
      Hyperhomocysteinemia (hyper-Hcy) is an established risk factor for deep venous
      thrombosis and stroke but has not been clearly associated with increased risk of
      CVT. We assessed the prevalence of hyper-Hcy and other thrombophilic risk factors
      in a population of 26 consecutive patients with non-pyogenic CVT, by review of a
      prospectively maintained database. The prevalences of hyper-Hcy and prothrombin
      G20210A, factor V G1691A and methylenetetrahydrofolate reductase (MTHFR) C677T
      mutations in these patients were compared with those in 100 healthy controls and
      100 patients with cerebroarterial disease. The prevalence of hyper-Hcy was
      greater in patients with CVT (10/26, 38.5%) than healthy controls (13/100; OR
      4.18, 95% CI 1.58-11.16) and comparable with that in patients with
      cerebroarterial disease (42/100). No significant differences were found in the
      prevalences of prothrombin or MTHFR mutation. No factor V mutation was found. Our
      findings indicate that hyper-Hcy is associated with an increased risk of CVT.
      Additional prospective cohort studies on large series of patients are required to
      clarify the time relationship between hyper-Hcy and the thrombotic event.

PMID- 15171738
TI  - A controlled prospective inception cohort study on the post-concussion syndrome
      outside the medicolegal context.
AB  - In an earlier historical cohort study on the post-concussion syndrome (PCS) in
      Lithuania, a country in which there are few confounding factors, the validity of
      this condition as a disease entity could not be confirmed. In order to register
      the post-traumatic symptoms, the influence of sociodemographic factors, and the
      effect of expectation on these symptoms more reliably, we performed a controlled
      prospective study. Three hundred subjects with concussion were followed up with
      repeated questionnaires for 1 year. For each study subject, a sex- and age
      matched control person with minor non-head injury was identified. These controls
      received similar questionnaires. Headache both after 3 months and after 1 year
      did not differ significantly between the head-injured participants and the non
      head-injured controls. Several other symptoms attributed to PCS did not differ
      significantly between the groups after 3 months. After 1 year the vast majority
      of symptoms did not differ significantly. Exceptions were slightly significant
      differences concerning memory problems, concentration problems, dizziness and
      tiredness. These differences were insignificant when analysing symptoms in
      unmarried and/or people with lower education, separately. No relationship between
      cognitive dysfunction and the severity of concussion was found. Although the
      possibility of a mild organic brain injury cannot be completely ruled out, our
      results cast doubt on the validity of PCS as a useful clinical entity, at least
      for head injuries with loss of consciousness for <15 min. Sociodemographic
      factors and expectation seem to influence reporting of symptoms after concussion.

PMID- 15171739
TI  - Stroke in the young as the clinical onset of non-Hodgkin's lymphoma with
      paraneoplastic endocarditis.

PMID- 15171740
TI  - Selective disappearance of essential tremor after ischaemic stroke.

PMID- 15171747
TI  - Intramyocellular lipids and insulin resistance.
AB  - Lipids are stored not only in adipocytes but also 'ectopically' in tissues such
      as muscle, liver, beta cells and others. From a metabolic perspective,
      intramyocellular lipids (IMCLs) have recently become a focus of interest. This
      review summarizes history, measurement techniques and interpretation of muscle
      lipid data. Problems in biopsies with the separation of those metabolically
      active lipid droplets in the cytoplasm of myocytes from further lipids in
      adipocytes are discussed as well as considerations important for analysis of
      correlations between IMCL content and insulin sensitivity under various
      circumstances. The relatively new approach to non-invasive assessment of the IMCL
      content by magnetic resonance spectroscopy (MRS) is described in detail and
      exemplary spectra from different skeletal muscle types in humans are presented.
      The MRS technique allows human examinations of large cohorts for a detailed
      assessment of the interactions among metabolic parameters such as age, measures
      of adiposity, hormonal and ethnic factors and insulin resistance. IMCLs are
      generally positively correlated with measures of obesity and negatively with
      insulin sensitivity. Paradoxically, physical fitness (maximal aerobic capacity)
      increases both IMCL content and insulin sensitivity and therefore has to be taken
      into account as a confounding factor. Intervention studies with MRS further
      allowed to elucidate the regulation of IMCL. Molecular mechanisms and potential
      genetic factors on IMCL regulation are discussed as well as possible mechanisms
      of current treatment strategies for improving insulin sensitivity.

PMID- 15171749
TI  - Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin
      is a marker of insulin resistance in obese adult males.
AB  - AIM: Plasma levels of corticosteroid-binding globulin (CBG) and sex hormone
      binding globulin (SHBG) may be regulated by insulin. The aim of this study was to
      test the hypothesis that these steroid-binding proteins are markers of insulin
      resistance and obesity in adult patients with the metabolic syndrome. METHODS:
      Fasting blood samples were obtained from 108 male and 88 female overweight adult
      patients who had varying degrees of dyslipidaemia, adiposity and insulin
      resistance. We measured plasma levels of SHBG and CBG and investigated their
      correlation with insulin resistance [homeostasis model assessment (HOMA) %
      sensitivity] and anthropometric markers of adiposity. RESULTS: In male patients,
      plasma SHBG correlated positively with HOMA (% sensitivity) and negatively with
      anthropometric measurements, including body mass index, waist circumference (cm)
      and percentage body fat. There was no correlation with CBG and any other
      parameter in the male patients. The female patients were treated as two groups,
      those not using oral contraceptives or hormone replacement therapy (n = 67) and
      those taking steroid medications (n = 21). Female patients using steroid
      medications had significantly higher SHBG levels but neither group showed any
      correlation between SHBG, insulin resistance and adiposity. Correlation studies
      of CBG with other parameters in the female subgroups did not reach statistical
      significance. CONCLUSIONS: We conclude that plasma SHBG is another surrogate
      marker for insulin resistance in obese males but not in obese females. It also
      appears that plasma CBG is not a useful marker of insulin resistance in patients
      with the metabolic syndrome.

PMID- 15171748
TI  - Relationship between C-reactive protein and visceral adipose tissue in healthy
      Japanese subjects.
AB  - AIM: Recent studies have suggested that the elevated C-reactive protein (CRP)
      levels are associated with body fat, especially visceral adipose tissue, but most
      of them were investigated in Westerners who had higher body mass index (BMI) than
      Asians. To investigate the association between CRP concentrations, parameters of
      visceral obesity, the insulin resistance syndrome and carotid atherosclerosis in
      healthy Japanese who had a lower BMI than Westerners. METHODS: We explored the
      relationships between fatness and visceral obesity parameters [by anthropometry,
      bioelectrical impedance analysis and abdominal computed tomography (CT)] and CRP
      (high sensitivity) and examined their associations with components of insulin
      resistance syndrome, interleukin-6 (IL-6), tissue necrosis factor-alpha (TNF
      alpha) and intima-media thickness (IMT) of common carotid arteries (CCAs) by
      ultrasonograms in 116 healthy Japanese subjects. RESULTS: In crude regression
      analyses, CRP was significantly associated with measures of obesity. After
      adjustment for age, gender and smoking, the association with CRP was stronger for
      parameters of visceral obesity (waist circumference, waist-to-hip ratio and
      visceral adipose tissue accumulation) than for other parameters of obesity. IL-6
      and TNF-alpha were not associated with CRP. Blood pressure (BP), metabolic
      variables and CCA-IMT were also significantly associated with CRP. But, after
      being adjusted for age, gender, smoking and BMI, BP and high-density lipoprotein
      cholesterol (HDLc) were significantly associated. CONCLUSION: CRP level is
      associated with visceral adipose tissue and is significantly associated with the
      components of insulin resistance syndrome in healthy Japanese subjects. These
      data support a possible role of visceral adipose tissue in inflammation component
      of atherosclerosis, and further studies are needed to study the mechanism of CRP
      elevation caused by visceral adipose tissue.

PMID- 15171750
TI  - Delayed gastric emptying in the obese: an assessment using the non-invasive (13)C
      octanoic acid breath test.
AB  - AIM: Much of the controversy surrounding the correlation between obesity and
      gastric emptying lies in the inconsistency of methodology and analysis. This
      study was designed to overcome some of the discrepancies encountered in previous
      studies and to test the hypothesis that obese individuals have altered gastric
      emptying compared to lean individuals. METHODS: Gastric emptying was measured
      using the (13)C-octanoic acid breath test in 16 lean and 16 obese women pair
      matched for age. Following an overnight fast, subjects were given a standard 2 MJ
      egg meal labelled with 100 microl of [1-(13)C]-octanoic acid. Breath samples were
      collected at regular intervals over a 6-h period. (13)C-isotopic enrichment in
      the breath was analysed using isotope ratio mass spectrometry and the data fitted
      to the established gastric emptying model. The lag times (t(lag)), half excretion
      times (t(1/2)), latency phase (t(lat)) and ascension times (t(asc)) were
      calculated. RESULTS: The mean t(1/2)-values (+/-standard error of the mean) were
      3.67 +/- 0.14 h and 4.23 +/- 0.18 h for lean and obese respectively, indicating
      significantly delayed gastric emptying in the obese (p = 0.019). The obese group
      also showed a significantly slower lag time (t(lag), p = 0.005) and latency phase
      (t(lat), p = 0.005), but no significant difference was found in the ascension
      time (t(asc), p = 0.154). Within groups, no correlation was found between half
      excretion times and body weight or half excretion times and body mass index.
      CONCLUSIONS: The present study demonstrated a prolonged lag phase and delayed
      gastric emptying in obese women when compared to lean women. This delay may be as
      a consequence of high-fat diets, a sedentary lifestyle and increased gastric
      distension associated with obesity, or a contributing factor in the pathogenesis
      of obesity resulting from the inactivation of gastrointestinal satiety signals
      and in an increase in food intake.

PMID- 15171752
TI  - Thiazolidinedione therapy in the prevention/delay of type 2 diabetes in patients
      with impaired glucose tolerance and insulin resistance.
AB  - AIM: The second-generation thiazolidinediones (TZDs), rosiglitazone and
      pioglitazone, significantly decrease fasting plasma glucose and glycosylated
      haemoglobin (HbA(1c)) levels in patients with diabetes. Recent studies suggest
      that early treatment with TZDs may prevent the progression from insulin
      resistance (IR) to type 2 diabetes mellitus (T2DM). This prospective analysis
      examined the effect of early TZD treatment in the prevention or delay of T2DM in
      a multiethnic population with impaired glucose tolerance (IGT) and IR. METHODS:
      The analysis included 172 patients (aged 29-86 years) with IGT and IR (normal or
      borderline HbA(1c), C-peptide levels > 2 mg/ml, fasting blood sugar 100-125
      mg/dl, and 2-h postprandial blood glucose levels 140-200 mg/dl). Patients in the
      active treatment group (n = 101) had received troglitazone for an average of 10
      months before being randomly switched to rosiglitazone (4 mg/day) or pioglitazone
      (30 mg/day). Patients were switched when troglitazone was withdrawn from the US
      market because of liver toxicity concerns. Patients with IGT and IR who received
      no antidiabetic medication served as a control group (n = 71). HbA(1c) and C
      peptide levels were measured at baseline (2 years) and study end point (3 years).
      Kaplan-Meier testing, using time to outcome as the main outcome variable,
      determined risk reduction in the TZD group relative to the control group.
      RESULTS: Mean HbA(1c) and C-peptide levels decreased for patients receiving
      either TZD at the 2-year assessment, and reductions were maintained at study end
      point. After 2 years, none of the patients receiving TZD therapy progressed to
      T2DM; three patients progressed to T2DM by study end point. In the control group,
      11 patients became diabetic after 2 years and 19 patients became diabetic by the
      end of the study. The incidence (risk reduction) of diabetes after 3 years was
      88.9% lower in the TZD group compared with the control group (p < 0.001).
      CONCLUSIONS: The TZDs, rosiglitazone and pioglitazone, were effective in reducing
      HbA(1c) and C-peptide levels in patients with IGT/IR. Progression of IR/IGT to
      T2DM appears to be significantly delayed or prevented with early TZD treatment.

PMID- 15171751
TI  - Increased expression of resistin and tumour necrosis factor-alpha in pig adipose
      tissue as well as effect of feeding treatment on resistin and cAMP pathway.
AB  - AIM: Resistin, a novel hormone, is expressed in mouse, rat and human adipose
      tissue. Its resistance to insulin is controversial. We hypothesized that resistin
      has the similar roles like those of tumour necrosis factor-alpha (TNF-alpha), a
      putative mediator of insulin resistance, and they are in common involved in
      regulating lipid metabolism in vivo. METHODS: We demonstrated TNF-alpha and
      resistin expression in different growth-stage adipose tissue of genetically lean
      and obese pigs using semiquantitative reverse transcriptase-polymerase chain
      reaction and Western blotting analysis. Moreover, we analysed the variations of
      resistin and some parameters associated with lipolysis pathway after body-weight
      reduction in feeding-restricted obese pigs. In addition, we localized resistin
      expression in the cell types from pig adipose tissue. RESULTS: Overall, the
      expression of TNF-alpha and resistin in obese pigs was statistically higher than
      their lean counterparts, although this difference in resistin mRNA expression
      tailed off with age. In individual pigs, their levels increased progressively
      with age and degree of obesity. After feeding restriction, resistin expression
      was gradually decreased. Simultaneously, feeding restriction also resulted in a
      significant decrease of serum triglyceride and plasma cAMP, free fatty acids and
      insulin as well as fat adenyl cyclase and cAMP. In addition, in isolated pig
      adipocytes, our data showed that resistin was localized not only to adipocytes
      but also to other unidentified stromal vascular cells. CONCLUSIONS: TNF-alpha and
      resistin are increased in obesity. Weight loss results in the decrease of
      resistin and lipolysis-associated parameters, suggesting the possible association
      between resistin and lipolysis pathway. Cell localization of resistin expression
      implies the possibility of other biological actions of resistin.

PMID- 15171754
TI  - Glucosamine-induced insulin resistance in L6 muscle cells.
AB  - BACKGROUND: Glucosamine increases flux through the hexosamine pathway, causing
      insulin resistance and disturbances similar to diabetic glucose toxicity. AIM:
      This study examines the effect of glucosamine on glucose uptake by cultured L6
      muscle cells as a model of insulin resistance. METHODS: Glucose uptake by L6
      myotubes was measured using the non-metabolized glucose analogue 2-deoxy-d
      glucose after incubation with glucosamine for 4 and 24 h, with and without
      insulin and several other agents (metformin, peroxovanadium and d-pinitol) that
      improve glucose uptake in diabetic states. RESULTS: After 4 h, high
      concentrations of glucosamine (5 x 10(-3) and 10(-2) M) reduced basal and insulin
      stimulated glucose uptake by up to 50%. After 24 h, the effect of insulin was
      completely abolished by 10(-2) M glucosamine and reduced over 50% by 5 x 10(-3) M
      glucosamine. Lower concentrations of glucosamine did not significantly alter
      glucose uptake. The effect of glucosamine could not be attributed to cytotoxicity
      assessed by the Trypan Blue test. Metformin, peroxovanadium and d-pinitol, each
      of which increased glucose uptake by L6 cells, did not prevent the decrease in
      glucose uptake with glucosamine. CONCLUSION: Glucosamine decreased insulin
      stimulated glucose uptake by L6 muscle cells, providing a potential model of
      insulin resistance with similarities to glucose toxicity. Insulin resistance
      induced by glucosamine was not reversed by three agents (metformin,
      peroxovanadium and d-pinitol) known to enhance or partially mimic the effects of
      insulin.

PMID- 15171753
TI  - Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin
      and hepatic enzymes of glucose metabolism in hyperglycaemic rats.
AB  - AIM: The present study was designed to investigate the effect of diasulin, a
      polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic
      glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar
      rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in
      this study. The rats were divided into seven groups after the induction of
      alloxan diabetes. In the experiment, six rats were used in each group. Group 1:
      normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of
      diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of
      saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of
      body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10
      g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin
      (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of
      glibenclamide (600 micro g/kg of body weight). The treatment was given for 30
      days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and
      the activities of hepatic glucose metabolic enzymes were determined in normal and
      experimental animals. RESULTS: Treatment with diasulin resulted in a significant
      reduction in blood glucose, glycosylated haemoglobin and an increase in plasma
      insulin and total haemoglobin and a significant improvement in glucose tolerance.
      Diasulin also resulted in a significant reduction in the activities of glucose-6
      phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of
      plasma insulin and hepatic hexokinase activity was significantly increased in
      alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that
      diasulin, a polyherbal drug, controls the blood glucose level by increasing
      glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic
      insulin than in untreated rats. This is possible, because it regulates the
      activities of hepatic glucose metabolic enzymes.

PMID- 15171755
TI  - Should we routinely measure a proxy for insulin resistance as well as improve our
      modelling techniques to better predict the likelihood of coronary heart disease
      in people with type 2 diabetes? For debate.

PMID- 15171756
TI  - Should we routinely measure a proxy for insulin resistance as well as improve our
      modelling techniques to better predict the likelihood of coronary heart disease
      in people with type 2 diabetes.

PMID- 15171757
TI  - Prolonged hypoglycaemia secondary to extended-release form glipizide.

PMID- 15171759
TI  - Recipient area hair direction and angle in hair transplanting.
AB  - BACKGROUND: A variety of recommendations for creating "natural" hair directions
      and angles in hair transplanting have been described. Objective. A method of
      accomplishing that goal is outlined. METHODS: Hair direction and angle are
      determined by multiple partings of the hair during the course of making recipient
      sites. Incisions are made to mimic such directions and angles. The direction is
      usually somewhat coronal and the use of grafts containing more than one
      follicular unit is particularly advantageous in producing a denser appearance.
      RESULTS: If the above technique is employed, one does not accelerate the rate at
      which existing hair in the recipient area is lost and the hair flows in a natural
      easy to manage fashion. CONCLUSION: Surgeons should nearly always mimic the scalp
      hair directions and angles seen in nature.

PMID- 15171760
TI  - Intricacies of the single-scar technique for donor harvesting in hair
      transplantation surgery.
AB  - BACKGROUND: Although single-scar techniques have been published and are used by
      approximately half of all surgeons, this approach is not as common as one might
      suspect. OBJECTIVE: The objective is to demonstrate several surgical gems that
      make the single-scar donor technique a viable method that can be performed by the
      vast majority of hair restoration surgeons. METHODS: The author presents various
      techniques such as postauricular skin elevation, subcutaneous undermining of the
      nape scalp, debulking of underlying scar tissue, temporary staple closure, and
      permanent double-layered closure using magnification (preferably 2.5 x or
      greater). All of these contribute to a loose closure with an aesthetically
      pleasing single donor scar after multiple surgeries. RESULTS: Utilizing the
      various techniques described in this article, the author has been able to achieve
      a cosmetically attractive single scar after multiple surgeries in the vast
      majority of patients. CONCLUSION: An aesthetically pleasing single, thin donor
      scar is preferable to multiple scars or a thick single scar at the donor area
      after multiple hair restoration surgical procedures. The author presents several
      methods that help hair restoration surgeons conquer some of the obstacles that
      have deterred them from performing a single-scar technique with consistently
      excellent results.

PMID- 15171761
TI  - The art of mixing follicular units and follicular groupings in hair restoration
      surgery.
AB  - BACKGROUND: Follicular grafting yields good results, but takes an excessively
      long time to perform the procedure. Iatrogenic damage can also occur to the
      follicular units during the dissection phase when two follicular units are very
      close together. OBJECTIVE: The objective was to minimize the length of time to
      perform the procedure and to limit iatrogenic damage to the follicular units
      during the dissection phase. METHODS: A donor strip is divided under a
      stereoscopic microscope into one-, two-, three-, and four-haired follicular units
      and three- and four-haired follicular groupings. Three- and four-haired
      follicular groupings are formed when 2 two-haired follicular units or a three
      haired follicular unit and one-haired follicular unit are very close together.
      These hair grafts are then inserted into incisions that are 1.0 to 2.5 mm in
      length and are arranged in accordance to the particular hairstyle desired by the
      patient. RESULTS: The technique used in this article accomplishes consistently
      excellent results while creating an environment that prevents damage to
      follicular units that are extremely close together. This technique requires less
      time and damages fewer follicular units. CONCLUSIONS: When performing hair
      restoration surgery, it is many times counterproductive to use follicular units
      exclusively.

PMID- 15171763
TI  - High-strength tretinoin for rapid retinization of photoaged facial skin.
AB  - BACKGROUND: Emollient creams of 0.02% and 0.05% tretinoin are currently used for
      improving the appearance of photoaged skin. At these concentrations, using this
      vehicle, the clinical results take many months. OBJECTIVE: The objective was to
      formulate and test a higher strength tretinoin that enhances penetration of the
      active molecule through the stratum corneum so that the clinical result is
      achieved after 1 month of treatment. METHODS: Thirty-two female subjects
      underwent treatment with 0.25% tretinoin solution applied nightly for 1 month.
      Subjects were evaluated clinically at baseline and 1, 2, and 4 weeks. Clinical
      grading was performed by comparing digital photographs before and after
      treatment. RESULTS: Almost all subjects improved on all measures of clinical
      grading (fine lines, mottled pigmentation, surface texture/roughness) by the end
      of the study. CONCLUSION: Tretinoin solution at a concentration of 0.25% is an
      effective and tolerable treatment for photodamaged facial skin and greatly
      shortens the time required for clinical response.

PMID- 15171762
TI  - Nonphysician practice of dermatologic surgery: the Texas perspective.
AB  - BACKGROUND: Increases in complications resulting from the nonphysician practice
      of dermatologic procedures have been reported nationally. This investigation was
      initiated owing to growing concern regarding the nonphysician practice of
      medicine in Texas. OBJECTIVE: The objective was to survey dermatologists in Texas
      to determine the number of patients seeking corrective treatment owing to
      complications from dermatologic procedures performed by nonphysicians. METHODS: A
      total of 488 dermatologists in Texas were surveyed and seven patients who
      experienced complications were interviewed by phone. RESULTS: Nearly 53% of
      responding physicians noted increased complications resulting from nonphysician
      practice of medicine. Approximately 33% of responding physicians reported that
      complications were known to have occurred in the absence of an on-site
      supervising physician. CONCLUSION: The increase in the number of complications
      owing to nonphysician practice of medicine in Texas mirrors the increases that
      have been reported nationally. The serious complications reported underscore the
      need for improved awareness and regulatory changes by state boards of medicine.

PMID- 15171764
TI  - Botulinum toxin a for aesthetic contouring of enlarged medial gastrocnemius
      muscle.
AB  - BACKGROUND: Oversized, muscular calves can cause psychological stress in women.
      Botulinum toxin A has been used in the treatment of benign masseteric hypertrophy
      with correction of the squared facial appearance. It is believed that botulinum
      toxin might also be effective in reducing enlarged calf muscles. OBJECTIVE: This
      study was performed to investigate the effect of botulinum toxin A in reducing
      enlarged medial gastrocnemius muscles in volunteers with muscular legs. METHODS:
      Botulinum toxin A of 32, 48, or 72 U was injected in each medial head of the
      gastrocnemius muscle in six women. Clinical photography was taken and the leg
      circumferences were measured. The functional evaluations were performed by
      examining range of joint motion and motor and sensory examination. RESULTS: All
      of the enrolled subjects showed a reduction in the medial gastrocnemius muscle
      after the botulinum toxin injection. The reduction in medial calf was noticed
      even after 1 week and the effect of was well maintained for 6 months. Leg
      contouring was obtained by the botulinum toxin treatment. The middle leg
      circumference showed a slight decrease in five subjects. No functional
      disabilities were observed. CONCLUSION: Botulinum toxin A can be used to contour
      the aesthetic enlargement of the medial gastrocnemius muscle with slight
      reduction in volume. Botulinum toxin-induced atrophy of the muscle caused no
      functional disabilities and the clinical improvement was well maintained for 6
      months after the botulinum toxin A injection.

PMID- 15171765
TI  - Treatment of neck lines and forehead rhytids with a nonablative 1540-nm Er:glass
      laser: a controlled clinical study combined with the measurement of the thickness
      and the mechanical properties of the skin.
AB  - BACKGROUND: Nonablative remodeling has been recently proposed as a new, no-down
      time, anti-aging treatment. Objective. The objective was to evaluate the efficacy
      and safety of nonablative skin remodeling with a 1540-nm Er:Glass laser on neck
      lines and forehead rhytids. METHODS: Twenty female patients (mean age 45 years)
      were enrolled. Skin thickness and mechanical properties were measured before the
      first treatment, 1 month after the third treatment, 1 month after the fifth
      treatment, and 3 months after the fifth treatment. RESULTS: All patients reported
      an improvement in both skin tone and texture. Using ultrasound imaging, dermal
      thickness of neck and forehead increased, respectively, by 70+/-13 microm
      (p<0.001) and 110+/-19 microm (p<0.003). A dramatic increase of initial stress of
      the forehead skin (firmness) was obtained, from 7.62+/-3.68 before treatment to
      16.68+/-7.44 3 months after the fifth treatment (p<0.0002). No immediate or late
      adverse effects were noted throughout the treatment regimen. CONCLUSION: This
      study demonstrates that irradiation with a 1540-nm Er:Glass laser emitting in a
      pulsed mode and coupled with an efficient contact cooling system increases dermal
      thickness and firmness, leading to a clinical improvement of neck lines and
      forehead rhydits.

PMID- 15171766
TI  - Study of the incidence and nature of "very subtle epidermal melasma" in relation
      to intense pulsed light treatment.
AB  - BACKGROUND: Skin rejuvenation with intense pulsed light (IPL) is effective for
      clearing epidermal pigment disorders. Complications are mild and limited to
      epidermal burns caused by excessive settings. Some patients, however, experience
      IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin.
      These patients seem to have very subtle epidermal melasma not visible to the
      naked eye. Ultraviolet photography has been useful in identifying these patients
      and preventing complications. OBJECTIVE: The study investigated the incidence of
      very subtle melasma in patients using UV photography, and assessed this tool in
      identifying high-risk patients. SUBJECTS AND METHODS: 223 Japanese women, 30-69
      years old, participated in the study. Very subtle melasma invisible to the naked
      eye under normal light was diagnosed by UV photography by two physicians, and any
      relationship among the disease incidence, age, and regular sunscreen use was
      examined. RESULTS: Sixty-three cases of very subtle melasma (28.3%) were
      identified among the 223 subjects, with a significantly lower incidence in
      sunscreen users. CONCLUSIONS: Patients diagnosed with subtle epidermal melasma
      and treated with mild IPL parameters did not suffer induced secondary
      hyperpigmentaion. To help avoid complications after treatment, IPL users should
      be aware of the age and sunscreen-related incidence of this phenomenon in Asian
      patients.

PMID- 15171767
TI  - Treatment of port wine stains with intense pulsed light: a prospective study.
AB  - BACKGROUND: Recent studies have shown that intense pulsed light can be useful in
      treating port wine stains that were resistant to previous pulsed dye laser
      therapy. Asian persons with high epidermal melanin context can be at a higher
      risk of complication. OBJECTIVE: The aim of this study was to conduct a
      prospective trial to assess the efficacy and complication of intense pulsed light
      in the treatment of port wine stains in Chinese patients. METHODS: Twenty-two
      Chinese patients with port wine stains without previous treatment were recruited
      to receive intense pulsed light source therapy for five to seven treatments at
      intervals of 3 to 4 weeks. Patient demographics, skin type, characteristics of
      port wine stains including color and location, treatment parameters, degree of
      pain caused by intense pulsed light treatment, percentage of clearing, and
      treatment complications were recorded and entered into a database. A
      questionnaire was conducted to assess the influence of treatment on daily
      activity and the intensity of pain experienced during treatment. RESULTS: There
      were 17 female and 5 male patients. Their ages ranged from 6 to 45 years with a
      mean age of 21.8+/-10.1 years. More than 90% of patients had more than 25% of
      clearing and the majority of patients (50%) had 25% to 50% of clearing. Although
      40% of the patients showed more than 50% clinical clearance, 9% of the patients
      were able to achieve more than 75% clearing. The only 2 patients with less than
      25% clearing had nodular port wine stains and no patient was able to achieve
      complete clearing. The procedures were well tolerated with a mean pain score of
      2.1+/-0.9 and the treatment had no influence on daily activity. One patient
      developed blisters and 6 patients had swelling for more than 24 hr that all
      resolved within 1 week without leaving permanent marks. They have been followed
      up from 12 to 27 months and there was no long-term complication. CONCLUSION:
      Intense pulsed light can be effective in treating port wine stains in Asian
      patients. In experienced hands, complications can be low and should be considered
      as one of the therapeutic options.

PMID- 15171768
TI  - Confocal microscopy study of nerves and blood vessels in untreated and treated
      port wine stains: preliminary observations.
AB  - BACKGROUND AND OBJECTIVE: Vascular ectasia in port wine stain birthmarks (PWS)
      might result from reduced innervation with loss of autonomic stimulation. We
      investigated this theory and evaluated nerve and blood vessel density, and mean
      blood vessel size in untreated and treated PWS skin. METHODS: Skin biopsy
      specimens were obtained from uninvolved skin, untreated PWS, PWS with a good
      response to laser treatment and PWS with a poor response to laser treatment.
      Confocal microscopy was performed to determine nerve and blood vessel density,
      and mean blood vessel size. RESULTS: Nerve density was significantly decreased in
      all PWS sites compared to uninvolved skin. Mean blood vessel diameter was larger
      in untreated compared to treated PWS. PWS with a good response to treatment had
      decreased nerve density but blood vessel density and mean diameter was relatively
      normal. PWS with a poor response to treatment had decreased nerve density but
      increased blood vessel density and mean blood vessel diameter compared to normal
      skin. CONCLUSION: Nerve density was decreased in all evaluated PWS sites and this
      may be a factor in lesion pathogenesis. PWS blood vessel size correlated with
      pulsed dye laser response and may prove to be a useful prognostic indicator of
      therapeutic outcome.

PMID- 15171770
TI  - Effectiveness of microporous polysaccharide hemospheres for achieving hemostasis
      in mohs micrographic surgery.
AB  - BACKGROUND: Microporous polysaccharide hemospheres consist of controlled-porosity
      spherical particles manufactured from bioinert plant polysaccharide. Microporous
      polysaccharide hemospheres facilitate hemostasis by rapidly absorbing the fluid
      component of blood, concentrating platelets and clotting factors to accelerate
      blood clotting. OBJECTIVE: The objective was to compare a microporous
      polysaccharide hemosphere bandage and electrocautery in achieving hemostasis.
      METHODS: Twenty-four patients with a total of 48 stages of Mohs micrographic
      surgery were included. Patients were stratified by whether or not they were
      taking anticoagulant medications. Within each group, patients were randomized to
      receive either the microporous polysaccharide hemosphere bandage or
      electrocautery. Outcomes included bleeding through the dressing (early time
      point) and active bleeding upon dressing removal (late time point). RESULTS:
      Nineteen patients not taking anticoagulants had 40 stages, of which 18 received
      the study bandage and 22 received electrocautery. The remaining 5 patients on
      anticoagulants had 8 stages, of which 4 received the study bandage and 4 received
      electrocautery. In both total and subgroup analysis, there was a higher incidence
      of bleeding through the dressing with the study bandage (p<0.05), but no increase
      in the incidence of active bleeding upon dressing removal (p>0.05). CONCLUSION:
      The microporous polysaccharide hemosphere study bandage had an increased
      incidence of bleeding through the dressing compared to electrocautery, but did
      not have an increased incidence of active bleeding upon dressing removal.

PMID- 15171769
TI  - Recurrent pigmented macules after q-switched alexandrite laser treatment of
      congenital melanocytic nevus.
AB  - BACKGROUND: Q-switch-mode laser treatment of congenital nevi does not result in
      complete histological clearance, and many patients have partial repigmentation
      within several months. In addition, the number of recurrent pigmented macules
      (RPMs) may increase, a major drawback to good cosmetic results. While the
      mechanism of recurrence is not known. OBJECTIVE: To help elucidate the mechanism
      of RPM development, we evaluated the expression of TNF-alpha and E-cadherin on
      RPM after treatment of congenital nevi with a Q-switched alexandrite laser
      (QSAL). METHODS: Thirteen Korean subjects with congenital nevi received QSAL
      treatment at intervals ranging from 2 to 6 months (mean, 4.5 treatments). Two
      millimeter punch biopsy specimens were obtained at their first visit and from
      RPMs 3-6 months after the last treatment. Expression of E-cadherin and TNF-alpha
      were determined histochemically in the original nevi and RPM. In addition, one
      RPM was examined by electron microscopy. RESULTS: Reduced pigmentation in the
      treated areas was seen in all cases, but partial repigmentaion was seen as black
      spots within 6 months after the last QSAL treatment. Compared to the original
      nevi, the RPMs had increased numbers of melanocytes in the epidermis and reduced
      nevomelanocytic nests in the dermis. The expression of TNF-alpha and E-cadherin
      was downregulated in the RPMs compared to the original nevi. Electron microscopy
      confirmed the increase in melanocytes in the epidermis of RPMs. CONCLUSION: Our
      findings suggest that the down-regulation of E-cadherin and TNF-alpha may induce
      the proliferation of melanocytes, resulting in the formation of RPMs.

PMID- 15171772
TI  - Objective changes in brow position, superior palpebral crease, peak angle of the
      eyebrow, and jowl surface area after volumetric radiofrequency treatments to half
      of the face.
AB  - BACKGROUND: Radiofrequency application through a proprietary device has recently
      been used for facial tissue tightening. Uniform volumetric heating of the dermis
      is created by passage of electrical current, while protection of the epidermis is
      maintained by concurrent cryogen cooling. OBJECTIVE: To objectively quantify the
      effectiveness of volumetric radiofrequency application on the face, we treated 10
      patients on the left side of the face with radiofrequency and evaluated the
      changes in brow position, superior palpebral crease, angle of the eyebrow, and
      jowl surface area. METHODS: Uniform treatments were applied at 134 J/cm(2) to the
      left side of the forehead and 1 cm past midline, at 115 J/cm(2) to the left side
      of temple and cheeks, and at 97 J/cm(2) to the left side of the jaw line and
      inferior postauricular surface. Patients were evaluated at monthly intervals up
      to 3 months with digital photography. Morphologic changes were evaluated with the
      "measuring tool" and "angle tool" of the Mirror Suite imaging system for aligned
      frontal-view photographs (for eyebrow position, superior palpebral crease
      elevation, and eyebrow angle changes) and the "outline tool" for aligned oblique
      view photographs (for jowl surface area changes). RESULTS: At the end of 3 months
      on the side that was treated, patients exhibited on average 4.3 mm of brow
      elevation and 1.9 mm of superior palpebral crease elevation along the
      midpupillary line and an average of 2.4 mm of brow elevation along the lateral
      canthal line. There was no significant improvement of brow elevation along the
      lateral canthal line on the contralateral side. The peak angle of the ipsilateral
      eyebrow became slightly more acute by an average of 4.5 degrees after treatments.
      Moreover, the jowls on the lower part of the face, displayed a mean decrease of
      22.6% in surface area after treatments. The nontreated side displayed a lack of
      eyebrow angle and jowl surface area changes. CONCLUSIONS: The application of
      radiofrequency to the face provides quantifiable changes. The brow along the
      midpupillary line is elevated to a greater degree than the lateral brow. This is
      consistent with acute angle changes seen in the eyebrow. Improvements in the
      lower part of the face with radiofrequency application can be quantified by
      demonstrating a decrease jowl surface. Moreover, these measurement techniques can
      be useful tools for evaluating other treatment parameters with radiofrequency
      application.

PMID- 15171771
TI  - Trilobed skin flap on the face: for reconstruction of full-thickness or
      commissural defects.
AB  - BACKGROUND: Although many local skin flaps have been described for reconstruction
      of defects on the face, there are still some difficulties in reconstruction of
      full-thickness defects of alar and ear region and commissural defects in
      periorbital and perioral region. OBJECTIVE: A trilobed skin flap can offer single
      stage reconstruction of difficult full-thickness or commissural defects. We
      performed trilobed skin flaps in reconstruction of the defects on the face. The
      design of the flap and outcomes of the procedures are presented. METHODS: Twelve
      patients with skin cancer on the face were operated under general or local
      anesthesia. After tumor resection, defects were closed with a trilobed skin flap.
      Patients were followed-up for a minimum 6 months. RESULTS: There was no early or
      late complication in all patients. Oral competence was achieved in reconstruction
      of the oral commissure. A new lateral canthus with angles as in the original one
      was created. Alar and ear reconstructions were performed at one session using the
      same flap without a graft. The outcome was satisfactory. CONCLUSION: Because it
      is easy to obtain a trilobed skin flap, it can be used for reconstruction of
      canthal, oral, and commissural defects, and the new canthus, mouth, and
      commissures with angles as in the original ones can be created. In addition, the
      flap can be used for reconstruction of full-thickness defects in the alar region
      and the ear.

PMID- 15171773
TI  - Lessons on dermoscopy: pigment network in nonmelanocytic lesions.

PMID- 15171774
TI  - Recalcitrant adverse reaction to vitamin K: response to pulsed dye laser.
AB  - BACKGROUND: Adverse cutaneous reaction to vitamin K manifests in sclerodermatous
      or erythematous plaque-like reactions. Most of the cases with erythematous plaque
      like dermatitis arising at the site of intramuscular vitamin K injection were
      recalcitrant and did not respond to various attempts with topical and
      intralesional corticosteroid. OBJECTIVE: The objective was to describe a 25-year
      old woman with recalcitrant adverse reaction owing to vitamin K who was
      successfully treated with pulsed dye laser. METHODS: Two consecutive pulsed dye
      laser treatments were performed 3 weeks apart with 450-microec pulse duration,
      585-nm pulse width, and fluence of 5 and 7 J/cm(2), respectively, using a 7-mm
      handpiece. RESULTS: One week after the second treatment, her skin lesion was
      cleared and she was followed without recurrence for 7 months. CONCLUSION:
      Although the precise mechanism remains yet to be proven, we have demonstrated
      successful treatment of localized adverse cutaneous reaction to vitamin K in one
      patient with the pulsed dye laser.

PMID- 15171775
TI  - Treatment of facial scarring and ulceration resulting from acne excoriee with 585
      nm pulsed dye laser irradiation and cognitive psychotherapy.
AB  - BACKGROUND: Self-inflicted skin ulcers and scars are often observed in patients
      with compulsive skin picking. The term "neurotic excoriation" has been used to
      describe this condition and may or may not coexist with other true skin
      pathologies, such as acne. The condition poses a diagnostic and treatment
      challenge because patients often also have an undiagnosed underlying psychologic
      disorder. CASE REPORTS: Two patients with numerous linear and stellate facial
      ulcers and hypertrophic and erythematous scars were diagnosed with acne excoriee
      in the setting of an obsessive-compulsive disorder linked to emotional stress and
      anxiety. The scars were treated with a 585-nm flashlamp-pumped pulsed dye laser
      using a 7-mm spot size, 1.5-msec pulse duration, and fluence range of 4.5 to 6.0
      J/cm(2). The patients received concomitant cognitive psychodynamic therapy to
      halt the cycle of impulse-driven skin picking and ulcer/scar formation. Marked
      clinical improvement of the scars and successful treatment of the acne excoriee
      were achieved with this combination approach. Relapses occurred when
      psychodynamic intervention was interrupted. CONCLUSION: The 585-nm flashlamp
      pumped pulsed dye laser improves the appearance of hypertrophic erythematous
      facial scars and ulcers in patients with severe acne excoriee. Proper diagnosis
      of underlying impulse-control disorders and ongoing psychodynamic therapy is
      necessary to maintain improvement.

PMID- 15171776
TI  - Elephantiasis nostras verrucosa successfully treated by surgical debridement.
AB  - BACKGROUND: Elephantiasis nostras verrucosa represents a rare group of cutaneous
      changes comprising dermal fibrosis, hyperkeratotic, verrucous, and papillomatous
      lesions after chronic secondary, nonfilarial lymphedema. There is no standard
      treatment for this rare cutaneous manifestation. OBJECTIVE: This article
      describes debridement that is helpful when performed in addition to
      physiotherapy. METHODS: We present a patient who was treated by shaving the
      verrucous area with a blade of a freehand knife and by subsequent abrading of the
      mossy area using a motor-powered grinder. RESULTS: Reepithelization was completed
      in 2 weeks. A compression stocking was used to treat the lymphedema. Ten months
      after the operation, we saw no signs of disease recurrence. The result was also
      aesthetically satisfactory. CONCLUSIONS: Surgery in such case may not always be
      the best treatment because it does not treat the cause of disease but only treats
      the cutaneous symptoms. Nevertheless, debridement is a rapid and an aesthetically
      acceptable form of treatment.

PMID- 15171777
TI  - Ocular melanoma metastatic to skin: the value of HMB-45 staining.
AB  - BACKGROUND: Cutaneous metastatic disease is an important finding that may
      represent the first sign of systemic cancer, or, if already known, that may
      change tumor staging and thus dramatically altered therapeutic plans. Although
      cutaneous metastases are relatively frequent in patients with cutaneous melanoma,
      they are less so from ocular melanoma. OBJECTIVE: To demonstrate the value of HMB
      45, staining in the detection of ocular melanoma metastatic to skin. METHODS: The
      immunohistochemical stain HMB-45 a monoclonal antibody directed against intact
      human melanoma cells, was employed on a skin biopsy specimen from a cutaneous
      tumor. RESULTS: HMB-45 staining was positive in the atypical hyperchromatic cells
      of the deep dermis. CONCLUSION: HMB-45 may be of value in the detection of ocular
      melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common
      and extremely important diagnosis. Although cutaneous metastases from cutaneous
      melanoma are relatively frequent, those from ocular melanomas are less so. Use of
      histochemical staining, especially the HMB-45 stain, allows confirmation of the
      diagnosis.

PMID- 15171779
TI  - The simplex (differentiated) variant of vulvar intraepithelial neoplasia.
AB  - BACKGROUND: The simplex (differentiated) variant of vulvar intraepithelial
      neoplasia is rarely reported. It is regarded as more likely than "classic"
      carcinoma in situ to be associated with invasion and can be easily mistaken for
      benign lesions. OBJECTIVE: The objective was to present a case of simplex variant
      of vulvar intraepithelial neoplasia in a 67-year-old woman that was initially
      misdiagnosed as lichen simplex chronicus. METHODS: A case report is reported and
      the literature is reviewed. RESULTS: Surgical excision with a free margin of 5 mm
      was performed and no evidence of recurrence was noted during the follow-up period
      of 6 months. CONCLUSION: The simplex vulvar intraepithelial neoplasia is an
      easily overlooked premalignant disease, and it can be cured with surgical
      treatment if diagnosed correctly and early.

PMID- 15171778
TI  - Telepathology as an aid in mohs micrographic surgery.
AB  - BACKGROUND: Mohs surgeons are occasionally confronted by challenging pathology
      ideally requiring the advice of a dermatopathologist. The Internet transmission
      of digital images of the pathology (telepathology) allows for such opinions to be
      easily and rapidly obtained. OBJECTIVE: The objective was to obtain images
      utilizing a digital camera focused directly through one microscope eyepiece with
      subsequent e-mail to a pathologist for an immediate opinion. METHODS: The
      particular area of interest on the slide is selected. The lens of the digital
      camera is placed directly on one eyepiece of the microscope and using the zoom
      and autofocus options of the camera a sharp image is obtained. The camera flash
      must be disabled. The images are immediately downloaded to computer and e-mailed
      to the pathologist for an opinion. RESULTS: Three case reports illustrate that
      the pathologist is able to offer suggestions on a diagnosis with a high degree of
      confidence using the e-mailed images. CONCLUSION: Digital camera technology now
      allows for images to be taken directly through an eyepiece of the microscope.
      These images can be almost instantaneously e-mailed to a pathologist anywhere in
      the world for an immediate opinion. The technique provides for greater surety
      where doubt exists about the pathology during Mohs surgery.

PMID- 15171780
TI  - Sentinel lymphadenectomy for circumscribed cutaneous T-cell lymphoma.
AB  - BACKGROUND: Sentinel lymphadenectomy has been associated with fewer complications
      in evaluating regional lymph nodes from melanoma or squamous cell carcinoma. It
      may also be employed in other malignancies such as localized cutaneous lymphoma.
      This is the first report demonstrating sentinel lymphadenectomy may be useful on
      primary cutaneous anaplastic large-cell lymphoma. OBJECTIVE: The objective was to
      assess the efficacy of sentinel lymphadenectomy on primary cutaneous anaplastic
      large-cell lymphoma. METHODS: Sentinel lymphadenectomy was performed on a patient
      with a localized CD30+ primary cutaneous anaplastic large-cell lymphoma. After
      preoperative lymphoscintigraphy, sentinel lymph node was identified by the gamma
      probe, excised totally, and sent for histopathologic examination. RESULTS:
      Sentinel lymphadenectomy was negative for tumor metastasis to sentinel lymph
      node. Total excision was performed without systemic chemotherapy or
      immunotherapy. This patient remained tumor-free 36 months after operation.
      CONCLUSION: Sentinel lymphadenectomy on patients with circumscribed restricted
      primary cutaneous lymphoma may be beneficial for staging and prognostication of
      the disease.

PMID- 15171782
TI  - Mohs tissue mapping and processing: a survey study.

PMID- 15171781
TI  - Metastatic microcystic adnexal carcinoma: an autopsy case.
AB  - BACKGROUND: Microcystic adnexal carcinoma is a clinically aggressive, local
      destructive sweat gland carcinoma with a high rate of recurrence, but regional or
      distant metastasis is quite rare. OBJECTIVE: The objective was to describe an
      autopsy case of microcystic adnexal carcinoma with hematogenous metastasis and
      perineural intracranial spreads. METHODS: This is an autopsy case of a 73-year
      old woman with hematogenous metastasis of microcystic adnexal carcinoma followed
      for more than 20 years. RESULT: The autopsy study revealed that the metastatic
      lesions were located in the perineural intracranial spread, left clavicle bone,
      bilateral 12th ribs, and liver. CONCLUSION: Physicians should be aware that
      microcystic adnexal carcinoma is capable of metastasis to the liver and bones
      with intracranial spread along the optic nerve into the cranium.

PMID- 15171783
TI  - Re: Webster-type short flap face-lifts versus submental rhytidectomy.

PMID- 15171784
TI  - Synchronous unilateral advancement flap.

PMID- 15171786
TI  - Food Advertising and Marketing Directed at Children and Adolescents in the US.
AB  - In recent years, the food and beverage industry in the US has viewed children and
      adolescents as a major market force. As a result, children and adolescents are
      now the target of intense and specialized food marketing and advertising efforts.
      Food marketers are interested in youth as consumers because of their spending
      power, their purchasing influence, and as future adult consumers. Multiple
      techniques and channels are used to reach youth, beginning when they are
      toddlers, to foster brand-building and influence food product purchase behavior.
      These food marketing channels include television advertising, in-school
      marketing, product placements, kids clubs, the Internet, toys and products with
      brand logos, and youth-targeted promotions, such as cross-selling and tie-ins.
      Foods marketed to children are predominantly high in sugar and fat, and as such
      are inconsistent with national dietary recommendations. The purpose of this
      article is to examine the food advertising and marketing channels used to target
      children and adolescents in the US, the impact of food advertising on eating
      behavior, and current regulation and policies.

PMID- 15171785
TI  - War-related psychological sequelae among emergency department patients in the
      former Republic of Yugoslavia.
AB  - BACKGROUND: Residents of the Republic of Serbia faced civil war and a NATO-led
      bombing campaign in 1999. We sought to assess the burden of metal health
      dysfunction among emergency department (ED) patients presenting for care three
      years post-war in Serbia. METHODS: This study was conducted during July and
      August 2002 at two sites: a university hospital ED in Belgrade, Serbia and an ED
      in a remote district hospital serving a Serbian enclave in Laplje Selo, Kosovo.
      Investigators collected data on a systematic sample of non-acute patients
      presenting to the ED. All respondents completed a structured questionnaire
      assessing demographics and symptoms of post-traumatic stress disorder (PTSD)
      (using the Harvard Trauma Questionnaire), and major depression (using the Center
      for Epidemiologic Studies Depression Scale). RESULTS: A total of 562 respondents
      participated (310 in Belgrade, 252 in Laplje Selo); the response rate was 83.8%,
      43% were female, and mean age was 37.6 years (SD = 13.4). Overall, 73 (13.0%)
      participants had symptoms consistent with PTSD, and 272 (49.2%) had symptoms
      consistent with depression. Sixty-six respondents had both disorders (11.9%). In
      separate multivariable logistic regression models, predictors of PTSD were
      refugee status and residence in Laplje Selo, and predictors of depression were
      older age, current unemployment, and lower social support. CONCLUSIONS: Three
      years post-war, symptoms of PTSD and major depression in Serbia remained a
      significant public health concern, particularly among refugees, those suffering
      subsequent economic instability, and persons living in rural, remote areas.

PMID- 15171788
TI  - Welcome to the International Journal of Behavioral Nutrition and Physical
      Activity (IJBNPA)!

PMID- 15171787
TI  - Why combine diet and physical activity in the same international research
      society?
AB  - Research in diet and physical activity in the U.S. started in very different
      traditions, with behavioral science input being uneven in their development.
      Investigators and policy makers in Europe have recognized the complementarity of
      diet and physical activity and incorporated them both under the label Public
      Health Nutrition. Joining these disciplines internationally offers the
      opportunity to benefit all, since the problems addressed are human, not specific
      to any one country.In regard to why combine diet and physical activity, at the
      biological level, there is reason to believe that diet and physical activity
      working in concert can remodel physiological structures and processes toward
      healthful ends. The diet and physical activity behaviors themselves vary in
      characteristics and are similar in others. The behavioral science components of
      these two disciplines face similar problems, and can learn from the advances made
      by the other, in the areas of measurement, correlates and intervention. By
      working together, knowledge will be enhanced from uncovering complementary and
      interactive relationships between diet and physical activity, and in relation to
      disease risks, that may result in designing more effective and efficient
      interventions and policies.Since the behavioral sciences are at a disadvantage in
      comparison to the biological sciences in terms of scientific advances and thereby
      capturing the popular imagination for solutions to health problems, we must
      redouble our efforts to enhance funding for behavioral research in regard to diet
      and physical activity and to make the research advances necessary to prevent the
      medicalizing of essentially social and behavioral problems. Nutrition and
      physical activity should most effectively do this together.

PMID- 15171789
TI  - 7-Ketocholesterol modulates intercellular communication through gap-junction in
      bovine lens epithelial cells.
AB  - BACKGROUND: Connexin43 (Cx43) is an integral membrane protein that forms
      intercellular channels called gap junctions. Intercellular communication in the
      eye lens relies on an extensive network of gap junctions essential for the
      maintenance of lens transparency. The association of Cx43 with cholesterol
      enriched lipid raft domains was recently demonstrated. The objective of this
      study is to assess if products of cholesterol oxidation (oxysterols) affect gap
      junction intercellular communication (GJIC). RESULTS: Primary cultures of lens
      epithelial cells (LEC) were incubated with 7-ketocholesterol (7-Keto), 25
      hydroxycholesterol (25-OH) or cholesterol and the subcellular distribution of
      Cx43 was evaluated by immunofluorescence confocal microscopy. The levels of Cx43
      present in gap junction plaques were assessed by its insolubility in Triton X-100
      and quantified by western blotting. The stability of Cx43 at the plasma membrane
      following incubation with oxysterols was evaluated by biotinylation of cell
      surface proteins. Gap junction intercellular communication was evaluated by
      transfer of the dye Lucifer yellow. The results obtained showed that 7-keto
      induces an accumulation of Cx43 at the plasma membrane and an increase in
      intercellular communication through gap junction. However, incubation with
      cholesterol or 25-OH did not lead to significant alterations on subcellular
      distribution of Cx43 nor in intercellular communication. Data further suggests
      that increased intercellular communication results from increased stability of
      Cx43 at the plasma membrane, presumably forming functional gap-junctions, as
      suggested by decreased solubility of Cx43 in 1% Triton X-100. The increased
      stability of Cx43 at the plasma membrane seems to be specific and not related to
      disruption of endocytic pathway, as demonstrated by dextran uptake. CONCLUSIONS:
      Results demonstrate, for the first time, that 7-keto induces an increase in gap
      junction intercellular communication, that is most likely due to an increased
      stability of protein at the plasma membrane and to increased abundance of Cx43
      assembled in gap junction plaques.

PMID- 15171790
TI  - Does harm reduction programming make a difference in the lives of highly
      marginalized, at-risk drug users?
AB  - Harm reduction is a controversial model for treating drug users, with little
      formal research available on its operation and effectiveness. In order to advance
      the field, we first conducted participatory research of harm reduction with 120
      clients using nominal-group technique to develop culturally relevant outcomes to
      measure progress. Second, we conducted focus group interviews with a different
      group of clients to help validate the outcomes. Third, we used the outcomes in an
      evaluation of the largest harm reduction program in New York City, which involved
      a representative sample of 261 and entailed baseline, post, and six follow-up
      assessments. The participatory research resulted in outcomes of 10 life areas
      important to drug users. Evaluation results showed that program participants made
      positive improvements across most outcomes, with the most substantial progress
      made in how clients dealt with drug-use problems. Along with their participation
      in the program, progress in some outcomes was also associated with clients' type
      of drug use (i.e., stable vs. chaotic), where more stable drug use was associated
      with better ways of making an income and types of housing. Surprisingly, progress
      was not associated with the kinds or numbers of services received or the length
      of time in the program. This was attributed to the service delivery model of harm
      reduction, in which clients are less inclined to associate their success with a
      single staff person or with a single service or intervention received than with
      the program as a whole.

PMID- 15171791
TI  - Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in
      vivo: CI-1040 strongly reduces growth and improves lung structure.
AB  - BACKGROUND: Signaling networks promoting cell growth and proliferation are
      frequently deregulated in cancer. Tumors often are highly dependent on such
      signaling pathways and may become hypersensitive to downregulation of key
      components within these signaling cascades. The classical mitogenic cascade
      transmits stimuli from growth factor receptors via Ras, Raf, MEK and ERK to the
      cell nucleus and provides attractive molecular targets for cancer treatment. For
      example, Ras and Raf kinase inhibitors are already in a number of ongoing phase
      II and phase III clinical trials. In this study the effect of the Raf kinase
      inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf
      dependent lung tumor mouse model was analyzed in detail. METHODS: We have
      generated a lung cancer mouse model by targeting constitutively active C-Raf
      kinase to the lung. These mice develop adenomas within 4 months of life. At this
      time-point they received daily intraperitoneal injections of either 100 mg/kg BAY
      43-9006 or CI-1040 for additional 21 days. Thereafter, lungs were isolated and
      the following parameters were analyzed using histology and immunohistochemistry:
      overall lung structure, frequency of adenoma foci, proliferation rate, ERK
      activity, caspase-3 activation, and lung differentiation. RESULTS: Both
      inhibitors were equally effective in vitro using a sensitive Raf/MEK/ERK ELISA.
      In vivo, the systemic administration of the MEK inhibitor CI-1040 reduced adenoma
      formation to a third and significantly restored lung structure. The proliferation
      rate of lung cells of mice treated with CL-1040 was decreased without any obvious
      effects on differentiation of pneumocytes. In contrast, the Raf inhibitor BAY 43
      9006 did not influence adenoma formation in vivo. CONCLUSION: The MEK inhibitor
      CI-1040 may be used for the treatment of Ras and/or Raf-dependent human
      malignancies.

PMID- 15171792
TI  - Elevated white cell count in acute coronary syndromes: relationship to variants
      in inflammatory and thrombotic genes.
AB  - BACKGROUND: Elevated white blood cell counts (WBC) in acute coronary syndromes
      (ACS) increase the risk of recurrent events, but it is not known if this is
      exacerbated by pro-inflammatory factors. We sought to identify whether pro
      inflammatory genetic variants contributed to alterations in WBC and C-reactive
      protein (CRP) in an ACS population. METHODS: WBC and genotype of interleukin 6
      (IL-6 G-174C) and of interleukin-1 receptor antagonist (IL1RN intronic repeat
      polymorphism) were investigated in 732 Caucasian patients with ACS in the OPUS
      TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken
      at baseline, i.e. Within 72 hours of an acute myocardial infarction or an
      unstable angina event. RESULTS: An increased white blood cell count (WBC) was
      associated with an increased C-reactive protein (r = 0.23, p < 0.001) and there
      was also a positive correlation between levels of beta-fibrinogen and C-reactive
      protein (r = 0.42, p < 0.0001). IL1RN and IL6 genotypes had no significant impact
      upon WBC. The difference in median WBC between the two homozygote IL6 genotypes
      was 0.21/mm3 (95% CI = -0.41, 0.77), and -0.03/mm3 (95% CI = -0.55, 0.86) for
      IL1RN. Moreover, the composite endpoint was not significantly affected by an
      interaction between WBC and the IL1 (p = 0.61) or IL6 (p = 0.48) genotype.
      CONCLUSIONS: Cytokine pro-inflammatory genetic variants do not influence the
      increased inflammatory profile of ACS patients.

PMID- 15171793
TI  - Correction: Stampidine prevents mortality in an experimental mouse model of viral
      hemorrhagic fever caused by lassa virus.

PMID- 15171794
TI  - The roles of segmental and tandem gene duplication in the evolution of large gene
      families in Arabidopsis thaliana.
AB  - BACKGROUND: Most genes in Arabidopsis thaliana are members of gene families. How
      do the members of gene families arise, and how are gene family copy numbers
      maintained? Some gene families may evolve primarily through tandem duplication
      and high rates of birth and death in clusters, and others through infrequent
      polyploidy or large-scale segmental duplications and subsequent losses. RESULTS:
      Our approach to understanding the mechanisms of gene family evolution was to
      construct phylogenies for 50 large gene families in Arabidopsis thaliana,
      identify large internal segmental duplications in Arabidopsis, map gene
      duplications onto the segmental duplications, and use this information to
      identify which nodes in each phylogeny arose due to segmental or tandem
      duplication. Examples of six gene families exemplifying characteristic modes are
      described. Distributions of gene family sizes and patterns of duplication by
      genomic distance are also described in order to characterize patterns of local
      duplication and copy number for large gene families. Both gene family size and
      duplication by distance closely follow power-law distributions. CONCLUSIONS:
      Combining information about genomic segmental duplications, gene family
      phylogenies, and gene positions provides a method to evaluate contributions of
      tandem duplication and segmental genome duplication in the generation and
      maintenance of gene families. These differences appear to correspond meaningfully
      to differences in functional roles of the members of the gene families.

PMID- 15171796
TI  - Evolutionary rate depends on number of protein-protein interactions independently
      of gene expression level: response.

PMID- 15171795
TI  - Comprehensive analysis of the base composition around the transcription start
      site in Metazoa.
AB  - BACKGROUND: The transcription start site of a metazoan gene remains poorly
      understood, mostly because there is no clear signal present in all genes. Now
      that several sequenced metazoan genomes have been annotated, we have been able to
      compare the base composition around the transcription start site for all
      annotated genes across multiple genomes. RESULTS: The most prominent feature in
      the base compositions is a significant local variation in G+C content over a
      large region around the transcription start site. The change is present in all
      animal phyla but the extent of variation is different between distinct classes of
      vertebrates, and the shape of the variation is completely different between
      vertebrates and arthropods. Furthermore, the height of the variation correlates
      with CpG frequencies in vertebrates but not in invertebrates and it also
      correlates with gene expression, especially in mammals. We also detect GC and AT
      skews in all clades (where %G is not equal to %C or %A is not equal to %T
      respectively) but these occur in a more confined region around the transcription
      start site and in the coding region. CONCLUSIONS: The dramatic changes in
      nucleotide composition in humans are a consequence of CpG nucleotide frequencies
      and of gene expression, the changes in Fugu could point to primordial CpG
      islands, and the changes in the fly are of a totally different kind and unrelated
      to dinucleotide frequencies.

PMID- 15171798
TI  - Delta: a new measure of agreement between two raters.
AB  - The most common measure of agreement for categorical data is the coefficient
      kappa. However, kappa performs poorly when the marginal distributions are very
      asymmetric, it is not easy to interpret, and its definition is based on
      hypothesis of independence of the responses (which is more restrictive than the
      hypothesis that kappa has a value of zero). This paper defines a new measure of
      agreement, delta, 'the proportion of agreements that are not due to chance',
      which comes from model of multiple-choice tests and does not have the previous
      limitations. The paper shows that kappa and delta generally take very similar
      values, except when the marginal distributions are strongly unbalanced. The case
      of the 2 x 2 tables (which admits very simple solutions) is considered in detail.

PMID- 15171799
TI  - Estimation of maximal reliability: a note on a covariance structure modelling
      approach.
AB  - A one-step covariance structure analysis procedure for estimation of maximal
      reliability of linear composites with congeneric measures is outlined. The
      approach is readily employed within a single modelling session using popular
      covariance structure analysis software, and permits simultaneous estimation of
      the optimal measure weights with standard errors. The method is illustrated by a
      numerical example.

PMID- 15171800
TI  - Bayesian analysis of two-level nonlinear structural equation models with
      continuous and polytomous data.
AB  - Two-level structural equation models with mixed continuous and polytomous data
      and nonlinear structural equations at both the between-groups and within-groups
      levels are important but difficult to deal with. A Bayesian approach is developed
      for analysing this kind of model. A Markov chain Monte Carlo procedure based on
      the Gibbs sampler and the Metropolis-Hasting algorithm is proposed for producing
      joint Bayesian estimates of the thresholds, structural parameters and latent
      variables at both levels. Standard errors and highest posterior density intervals
      are also computed. A procedure for computing Bayes factor, based on the key idea
      of path sampling, is established for model comparison.

PMID- 15171801
TI  - Fechner as a statistician.
AB  - The work of Gustav Theodor Fechner (1801-1887) related to probability and
      statistics and, in particular, to the treatment of observations is described.
      From a mathematical point of view his arguments were often insufficient, but his
      work proved to be highly fruitful, and the relevant comments of such scholars as
      Pearson and von Mises are presented. As the originator of psychophysics, Fechner
      opened up a new field for quantification. Subsequent workers rejected some of his
      findings, while at the same time acknowledging their debt to him.

PMID- 15171797
TI  - Multisite phosphorylation of Pin1-associated mitotic phosphoproteins revealed by
      monoclonal antibodies MPM-2 and CC-3.
AB  - BACKGROUND: The peptidyl-prolyl isomerase Pin1 recently revealed itself as a new
      player in the regulation of protein function by phosphorylation. Pin1 isomerizes
      the peptide bond of specific phosphorylated serine or threonine residues
      preceding proline in several proteins involved in various cellular events
      including mitosis, transcription, differentiation and DNA damage response. Many
      Pin1 substrates are antigens of the phosphodependent monoclonal antibody MPM-2,
      which reacts with a subset of proteins phosphorylated at the G2/M transition.
      RESULTS: As MPM-2 is not a general marker of mitotic phosphoproteins, and as most
      mitotic substrates are phosphorylated more than once, we used a different
      phosphodependent antibody, mAb CC-3, to identify additional mitotic
      phosphoproteins and eventual Pin1 substrates by combining affinity purification,
      MALDI-TOF mass spectrometry and immunoblotting. Most CC-3-reactive
      phosphoproteins appeared to be known or novel MPM-2 antigens and included the RNA
      binding protein p54nrb/nmt55, the spliceosomal protein SAP155, the Ki-67 antigen,
      MAP-1B, DNA topoisomerases II alpha and beta, the elongation factor hSpt5 and the
      largest subunit of RNA polymerase II. The CC-3 mitotic antigens were also shown
      to be Pin1 targets. The fine CC-3- and MPM-2-epitope mapping of the RNA
      polymerase II carboxy-terminal domain confirmed that the epitopes were different
      and could be generated in vitro by distinct kinases. Finally, the post-mitotic
      dephosphorylation of both CC-3 and MPM-2 antigens was prevented when cellular
      Pin1 activity was blocked by the selective inhibitor juglone. CONCLUSION: These
      observations indicate that the mitotic phosphoproteins associated with Pin1 are
      phosphorylated on multiple sites, suggesting combinatorial regulation of
      substrate recognition and isomerization.

PMID- 15171802
TI  - On the chi-square approximation to the exact distribution of goodness-of-fit
      statistics in multinomial models with composite hypotheses.
AB  - Multinomial models are increasingly being used in psychology, and this use always
      requires estimating model parameters and testing goodness of fit with a composite
      null hypothesis. Goodness of fit is customarily tested with recourse to the
      asymptotic approximation to the distribution of the statistics. An assessment of
      the quality of this approximation requires a comparison with the exact
      distribution, but how to compute this exact distribution when parameters are
      estimated from the data appears never to have been defined precisely. The main
      goal of this paper is to compare two different approaches to defining this exact
      distribution. One of the approaches uses the marginal distribution and is,
      therefore, independent of the data; the other approach uses the conditional
      distribution of the statistics given the estimated parameters and, therefore, is
      data-dependent. We carried out a thorough study involving various parameter
      estimation methods and goodness-of-fit statistics, all of them members of the
      general class of power-divergence measures. Included in the study were
      multinomial models with three to five cells and up to three parameters. Our
      results indicate that the asymptotic distribution is rarely a good approximation
      to the exact marginal distribution of the statistics, whereas it is a good
      approximation to the exact conditional distribution only when the vector of
      expected frequencies is interior to the sample space of the multinomial
      distribution.

PMID- 15171803
TI  - The meta-analysis of partial effect sizes.
AB  - This paper discusses the synthesis of partial effect sizes derived from
      multivariate settings. The general statistical properties of the d-effect size
      are derived, extending Hedges's statement of zero-order properties. These general
      properties have direct relevance in the synthesis of a set of independent effect
      sizes arising from empirical studies predicated on a common theoretical model. We
      discuss possible solutions to the problem of comparing effect sizes arising from
      models employing differing sets of covariates. We apply the general statistical
      properties in the synthesis of gender performance differences in first-level
      economics courses at three New Zealand universities. The model of academic
      performance is based on Spearman's conception of general academic ability and
      specific ability in economics.

PMID- 15171804
TI  - Bayesian model comparison of nonlinear structural equation models with missing
      continuous and ordinal categorical data.
AB  - Missing data are very common in behavioural and psychological research. In this
      paper, we develop a Bayesian approach in the context of a general nonlinear
      structural equation model with missing continuous and ordinal categorical data.
      In the development, the missing data are treated as latent quantities, and
      provision for the incompleteness of the data is made by a hybrid algorithm that
      combines the Gibbs sampler and the Metropolis-Hastings algorithm. We show by
      means of a simulation study that the Bayesian estimates are accurate. A Bayesian
      model comparison procedure based on the Bayes factor and path sampling is
      proposed. The required observations from the posterior distribution for computing
      the Bayes factor are simulated by the hybrid algorithm in Bayesian estimation.
      Our simulation results indicate that the correct model is selected more
      frequently when the incomplete records are used in the analysis than when they
      are ignored. The methodology is further illustrated with a real data set from a
      study concerned with an AIDS preventative intervention for Filipina sex workers.

PMID- 15171805
TI  - Three Mahalanobis distances and their role in assessing unidimensionality.
AB  - Unidimensionality is the hallmark psychometric feature of a well-constructed
      measurement scale. However, in determining the degree to which a set of items
      form a unidimensional scale, aberrant item response patterns may distort our
      investigations. For example, aberrant response patterns may adversely impact
      interitem covariances which, in turn, can distort estimates of a scale's
      dimensionality and reliability. In this study, we investigate and compare the
      utility of three Mahalanobis distance (M-distance) measures in identifying and
      downweighting aberrant item response patterns. Our findings indicated that a
      residual-based M-distance measure had the best properties. Specifically, response
      patterns having greater residual-based M-distances were responsible for observed
      violations of unidimensionality. When these response patterns were properly
      downweighted according to this M-distance, the data fitted a one-factor model
      better and scale reliability increased. The procedures are illustrated using
      three real data sets.

PMID- 15171806
TI  - A note on alternative parameterizations of a model for evaluating agreement
      between two tests.
AB  - The agreement between two competing tests which purport to measure the same trait
      is a common concern in test development. In this paper three alternative
      parameterizations of the measurement model useful in this context are presented.
      Both one-factor and two-factor approaches are applied. Lord's classic example,
      where the main problem is to investigate whether time limits represent an extra
      speed component in a vocabulary test, is used to illustrate the ideas.

PMID- 15171807
TI  - A note on preliminary tests of equality of variances.
AB  - Preliminary tests of equality of variances used before a test of location are no
      longer widely recommended by statisticians, although they persist in some
      textbooks and software packages. The present study extends the findings of
      previous studies and provides further reasons for discontinuing the use of
      preliminary tests. The study found Type I error rates of a two-stage procedure,
      consisting of a preliminary Levene test on samples of different sizes with
      unequal variances, followed by either a Student pooled-variances t test or a
      Welch separate-variances t test. Simulations disclosed that the twostage
      procedure fails to protect the significance level and usually makes the situation
      worse. Earlier studies have shown that preliminary tests often adversely affect
      the size of the test, and also that the Welch test is superior to the t test when
      variances are unequal. The present simulations reveal that changes in Type I
      error rates are greater when sample sizes are smaller, when the difference in
      variances is slight rather than extreme, and when the significance level is more
      stringent. Furthermore, the validity of the Welch test deteriorates if it is used
      only on those occasions where a preliminary test indicates it is needed. Optimum
      protection is assured by using a separate-variances test unconditionally whenever
      sample sizes are unequal.

PMID- 15171808
TI  - Statistical software review.

PMID- 15171811
TI  - History and diagnostic value of antibodies to citrullinated proteins in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic inflammatory joint disease characterized by the
      presence of autoantibodies. The best known autoantibody is the rheumatoid factor.
      Another group of antibodies directed against citrullinated epitopes is proven to
      be more specific for rheumatoid arthritis. This review gives an overview of the
      history of the different anti-citrullinated protein antibody detection methods
      and their diagnostic and prognostic properties in RA.

PMID- 15171810
TI  - Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral
      activities.

PMID- 15171812
TI  - Macrophage-targeted photodynamic therapy.
AB  - Photodynamic therapy (PDT) uses light activatable molecules that after
      illumination produce reactive oxygen species and unwanted tissue destruction. PDT
      has dual selectivity due to control of light delivery and to some extent
      selective photosensitizer (PS) accumulation in tumors or other diseased tissue,
      additional targeted selectivity of PS for disease is necessary. The delivery of
      drugs to selected lesions can be enhanced by the preparation of targeted
      macromolecular conjugates that employ cell type specific targeting by ligand
      receptor recognition. Macrophages and monocytes express a scavenger-receptor that
      is a high-capacity route for delivering molecules into endocytic compartments in
      a cell-type specific manner. We have shown that by attaching PS to scavenger
      receptor ligands it is possible to get three logs of selective cell killing in
      macrophages while leaving non-macrophage cells unharmed. The capability to
      selectively kill macrophages has applications in treating cancer and in the
      detection and therapy of vulnerable atherosclerotic plaque and possibly for
      autoimmune disease and some infections.

PMID- 15171813
TI  - Immune-signalling by orally-delivered probiotic bacteria: effects on common
      mucosal immunoresponses and protection at distal mucosal sites.
AB  - Probiotics--orally-delivered preparations of non-pathogenic bacterial cells--have
      been reported to increase anti-microbial protection in the gastrointestinal tract
      environment, and offer a safe and effective non-pharmaceutical means for
      combating infectious diseases and certain other pathologies. There is also an
      increasing body of evidence to suggest that immunostimulation by probiotic
      bacteria in the gut can enhance immune protection at distal mucosal sites, such
      as the urogenital and respiratory tracts. This review summarises the current
      information, from both clinical and animal model studies, of a role for orally
      delivered probiotics in modulating mucosal immunoresponses and protection at
      distal sites. While it is clear that probiotics hold promise in this area,
      research that is targeted toward identifying the mechanism driving stimulation of
      the common mucosal immune system, as well as patterns of mucosal tissue homing by
      immunocytes following probiotic-mediated signalling in the gut, is strongly
      encouraged.

PMID- 15171814
TI  - Immunological features of neurological paraneoplastic syndromes.
AB  - Neurological paraneoplastic syndromes are a rare group of disorders that occur in
      1-2% of people with malignancy. They are usually caused by an immune response,
      triggered by and directed against a tumour, that cross-reacts with protein
      expressed by the peripheral or central nervous system. Any part of the nervous
      system can be affected and patients often develop severe and permanent
      disability. Diagnosis can be difficult as in two-thirds of patients the
      neurological problems appear up to 5 years before the tumour manifests. However,
      certain of these syndromes are often associated with specific serum
      autoantibodies that can be useful both in diagnosis of the neurological syndrome
      and in focusing the search for a particular tumour. Thus, these antibodies can
      allow earlier identification and treatment of cancer and, potentially, a
      reduction in morbidity and mortality. It was only in the 1980s that the first
      anti-neuronal autoantibodies were characterized and their associations with
      clinical syndromes and tumours defined. Further antibodies have been isolated
      over the past 20 years and novel pathogenic mechanisms for several syndromes have
      been recognized. For example, voltage-gate ion channels seem to be a common
      target for autoantibodies involved in peripheral nerve diseases such as the
      Lambert-Eaton myasthenic syndrome and neuromyotonia (Isaacs' syndrome). However,
      the place of most paraneoplastic antibodies in the pathogenesis of central
      syndromes is yet to be fully elucidated.

PMID- 15171815
TI  - Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and
      serum amyloid A via the common lipoxin A receptor.
AB  - Lipoxin A4 (LXA4) is a potent eicosanoid that inhibits IL-1beta-induced
      activation of human fibroblast like synoviocytes (FLS) via the ALX4 receptor.
      Serum amyloid A (SAA) is an acute phase reactant with cytokine-like properties.
      SAA has been shown to bind the same seven transmembrane G protein-coupled
      receptor ligated by LXA4. Here we compared the inflammatory responses of lipid
      (LXA4) and peptide (SAA) ligands in human FLS via the shared ALX, and
      characterized their downstream signaling. LXA4 induced stimulation of tissue
      inhibitors of metalloproteinase-2, whereas SAA induced interleukin-8 and matrix
      metalloproteinase-3 production. SAA up-regulated NF-kappaB and AP-1 DNA binding
      activity, while LXA4 markedly inhibited these responses after IL-1beta
      stimulation. A human IL-8 promoter luciferase construct was transfected into CHO
      cells stably expressing ALXR in order to determine the role of NF-kappaB and/or
      AP-1 in the regulation of IL-8 gene expression. The NF-kappaB pathway proved to
      be the preeminent for the biological responses elicited by both ligands. These
      findings suggest that two endogenous molecules, targeting a common receptor,
      could participate in the pathogenesis of inflammatory arthritis by differentially
      regulating inflammatory responses in tissues expressing the ALXR.

PMID- 15171816
TI  - Quantification of neurotrophin mRNA expression in PMN mouse: modulation by
      xaliproden.
AB  - Compounds possessing neurotrophic properties may represent a possible treatment
      for neurodegenerative disorders such as amyotrophic lateral sclerosis. Xaliproden
      (SR57746A), an orally-active non-peptide compound, which has been found to
      exhibit neurotrophic effects in vitro and in vivo, increased the lifespan and
      delayed the progression of the motor neuron degeneration in PMN mice. We have
      used a quantitative reverse transcription/polymerase chain reaction amplification
      technique to study the regulation of neurotrophin mRNA and trk mRNA expression in
      PMN mice. NGF and NT-3 mRNA are downregulated in PMN mice. These deficiencies can
      be overcome by a treatment with xaliproden. Such an effect could contribute to
      neurotrophic effects of xaliproden in vivo and in vitro.

PMID- 15171817
TI  - Integrin beta2-chain (CD18) over-expression on CD4+ T cells and monocytes after
      ischemia/reperfusion in patients undergoing primary percutaneous
      revascularization.
AB  - beta2-integrin subunit (CD18) plays an essential role in leukocyte recruitment
      and adhesion in sites of endothelial injury. We analyzed the surface expression
      of CD18 on T lymphocytes and monocytes in a series of patients presenting acute
      coronary syndrome (ACS) who underwent primary percutaneous intervention (PCI) for
      coronary artery revascularization. We found that basal CD18 expression on
      peripheral blood-derived CD4+ (but not CD8+) T lymphocytes was significantly
      increased in ACS patients as compared with age-matched healthy volunteers. During
      primary PCI, a significant increase in CD18 molecule density was detected
      immediately after balloon deflation (reperfusion) on both CD4+ T cells and
      monocytes obtained from the right atrium (RT) as compared with basal values.
      These data suggest that upregulation of CD18 molecules plays an important role in
      local recruitment of CD4+ T cells and monocytes to the site of endothelial damage
      after ischemia/reperfusion, therefore being responsible, at least in part, for
      the inflammatory-mediated complications associated with primary PCI.

PMID- 15171818
TI  - The expression of LEC/CCL16, a powerful inflammatory chemokine, is upregulated in
      ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease of unknown aetiology
      and pathogenesis. The presence in the colonic mucosa of reactive cells expressing
      proinflammatory cytokines and chemokines is associated with high levels of IL-10,
      an anti-inflammatory cytokine. Our aim was to investigate the role of IL-10 and
      the beta chemokine LEC/CCL16 selectively up-regulated by IL-10 in inflammatory
      cell recruitment and cytokine and chemokine production during UC. We studied
      histologically, immunohistochemically and ultrastructurally colonic biopsies from
      20 active UC patients and 10 control specimens taken far from any macroscopically
      detectable lesion in age and sex-matched patients with noninflammatory bowel
      disease. In active UC, immature dendritic cells (DCs) in the LP are associated
      with IL-10 in the T cell rich area. Furthermore, most of the LP-infiltrating
      macrophages strongly expressed LEC/CCL16, a chemokine upregulated by IL-10. To
      evaluate if LEC/CCL16 plays a role in the inflammatory reaction present in UC, we
      performed morphological studies in mice injected s.c. with syngeneic tumor cells
      engineered to produce LEC/CCL16. We found that the LEC protein locally released
      by LEC-gene-transfected tumor cells is a potent proinflammatory chemokine that
      induces the recruitment of a reactive infiltrate, and an angiogenic process
      mirroring that in human UC.

PMID- 15171819
TI  - Caspase-3 is dually regulated by apoptogenic factors mitochondrial release and by
      SAPK/JNK metabolic pathway in leukemic cells exposed to etoposide-ionizing
      radiation combined treatment.
AB  - Ionizing radiation induces a series of multiple intracellular events which can
      lead to activation of caspases, cytoplasmic proteases involved in the occurrence
      of apoptosis. The response of leukemic cells to ionizing radiation is amplified
      when they have been pre-treated with the anticancer drug etoposide, therefore the
      aim of this work has been to establish the lowest etoposide concentration
      combined with the lowest ionizing radiation dose to obtain the best
      antineoplastic response. Two leukemic cell lines, HL-60 and Jurkat, employed in
      this study demonstrated different sensitivities to ionizing radiation and to
      etoposide treatment, with Jurkat T cells requiring a higher dose (1 microM) to
      display cell cycle perturbation and apoptotic DNA damage similar to those seen in
      HL-60. We hypothesize that this kind of response could be mediated by
      mitochondrial release of apoptogenic factors and by SAPK/JNK metabolic pathway
      activation, both leading to caspase-3 cleavage. All in all these results provide
      insight into the sensitivity or resistance of leukemic cells to antineoplastic
      agents and identify molecular targets for rational therapeutic intervention
      strategies.

PMID- 15171820
TI  - Response of ADA and its isoenzymes in mice infected by Trichinella spiralis and
      treated with mimosine.
AB  - Infections caused by the nematode Trichinella spiralis (T. spiralis) are
      characterized by an inflammatory response in the host. The aim of this study was
      to identify and evaluate markers for monitoring mice infected with T. spiralis
      and treated with or without mimosine. The markers that have been used were total
      and differential white blood cell counts, subpopulations of lymphocytes, serum
      tADA and its isoenzymes ADA1 and ADA2 activity. The study included 3 groups of
      BALB/c mice. Group A consisted of 16 healthy mice, Group B of 16 mice infected
      with T. spiralis and treated with saline, and Group C of 16 mice infected with T.
      spiralis and treated with mimosine. The measurements were made once per week for
      the first six weeks continuously following the infection. According to our
      results, leukocytosis, lymphocytosis and increased percentages of adhesion
      molecules and CD4 lymphocytes were present in groups B and C one week post
      infection. Total ADA activity as well as ADA1 and ADA2 was higher in groups B and
      C versus group A from the first week post-infection. The levels of tADA activity,
      ADA1 and ADA2 were higher in group B compared to those of group C and the
      difference was statistically significant (p<0.05) during the 4th week post
      infection. The majority of tADA activity, essential for an efficient immune
      response, was derived from ADA1 which may have been produced by infected tissues.
      The elevated activities of tADA and ADA1 may be sensitive markers for infection
      of T. spiralis and for monitoring the course of the infection.

PMID- 15171821
TI  - Do tryptase, ECP and specific IgE measurement by nasal incubation increase the
      specific nasal provocation test sensitivity?
AB  - The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool.
      Fitted to reproduce natural exposure condition to pick the responsible allergen
      for nasal symptoms out, it is applied when prick test and RAST responses are
      doubtful. SNPT results have been evaluated measuring nasal resistance (anterior
      rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity.
      This study focused on the determination of allergic response markers, triggered
      by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil
      Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients
      suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were
      enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal
      mucosa applying a new method, based on in situ incubation, before and after sNPT.
      The latter was performed following a standardized method. Tryptase levels
      increased in 13 patients (65%), were unchanged in four patients (20%), and
      slightly decreased in three patients (15%). The increase recorded was significant
      in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen
      allergic patients. ECP values increased in 13 patients (65%), were unchanged in
      two patients (10%), and highly decreased in five patients (25%). ECP increase was
      not significant (p> 0.05). Specific IgE levels increased in seven patients (35%),
      were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE
      increase was significant in pollen-allergic patients (p<0.05), while it was not
      significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE
      were not detected in the control group. The data obtained showed a positive sNPT
      response in 12 patients (60%). Comparing our results with those derived from
      classical-parameter employment, we gathered an improvement of 10%. On the basis
      of the usual parameters, in fact, we recorded 50% positivity, while the use of
      mediators provided an additional 10% improvement in sNPT sensitivity: taking
      together the usual parameters and nasal allergic mediators values, we reached an
      sNPT over-all sensitivity of 85%.

PMID- 15171822
TI  - Chlamydia pneumoniae infection in patients with acute coronary syndrome: a
      clinical and serological 1-year follow-up.
AB  - The role of Chlamydia pneumoniae infection in pathogenesis and prognostic
      stratification of patients with acute coronary syndromes is still unclear.
      However, a limitation of many studies is the evaluation of the long-term
      prognostic role of a sample obtained during the acute phase, whereas the
      assessment of the temporal trend of antibody titers could be more useful. One
      hundred and fourteen consecutive patients with acute coronary syndromes (71 with
      acute myocardial infarction and 43 with unstable angina) were studied. Blood
      samples were obtained immediately after hospital admission and 1, 3, 6 and 12
      months after the acute event. The microimmunofluorescence test was used to detect
      C. pneumoniae specific antibodies. The incidence of new coronary events (death,
      myocardial infarction, recurrent angina) was recorded during the 1-year follow-up
      period. No significant difference was found between patients with (n = 35) or
      without (n = 79) new coronary events (N.C.E.) regarding baseline and serial
      values of C. pneumoniae antibodies. The rate of high titers at any time of follow
      up was also similar in the two groups: IgG > or =1:512 were present in 52%, 64%,
      55% and 32% of N.C.E.+ patients, and in 48%, 54%, 52% and 36% of N.C.E.- patients
      at 1, 3, 6 and 12 months respectively; IgA > or =1:256 were present in 26%, 23%,
      30% and 23% of N.C.E.+ patients and in 20%, 30%, 25% and 19% of N.C.E.- patients
      at 1, 3, 6 and 12 months respectively. Our data indicate that elevated titers of
      C. pneumoniae antibodies, even with a serial 1-year evaluation, are not a
      predictor of future coronary events in patients with acute myocardial infarction
      or unstable angina.

PMID- 15171824
TI  - Asthma worsened by benzoate contained in some antiasthmatic drugs.
AB  - Here, we report our experience on benzoate hypersensitivity. Drug and food
      additives are known to induce pseudo-allergic reactions such as urticaria,
      eczema, asthma and rhinitis. These reactions are often under-diagnosed, above all
      in allergic patients treated with additive containing drugs. On the contrary,
      attention to the additives present in some drug formulations and foods may often
      permit more correct diagnosis.

PMID- 15171823
TI  - Multicentric study of seroprevalence of Borrelia burgdorferi and Anaplasma
      phagocytophila in high-risk groups in regions of central and southern Italy.
AB  - The aim of this study was to evaluate the seroprevalence of B. burgdorferi and A.
      phagocytophila in populations of workers from 4 Italian regions, known to be
      exposed to tick bites. A total of 712 serum samples collected were divided as
      follows: 387 samples were obtained from workers at risk for tick bites and 325
      from individuals that were not considered to be at risk of ticks bites and served
      as the control group. Antibodies against B. burgdorferi were found in 29 (7.5%)
      of the 387 risk workers and in 4 (1.2%) of the 325 control group. Antibodies
      reactive with the HGE agent were found in 22 (5.7%) of the 387 risk workers and
      in 3 (0.9%) of the 325 control group. Antibodies to both B. burgdorferi and A.
      phagocytophila were found in 1.6% of the forestry workers confirming the
      possibility of coinfection or concurrent infection. The present finding show
      significant differences between seroprevalence of the risk workers and that of
      the people with no risk for tick exposure.

PMID- 15171825
TI  - Acquired haemophilia masked by heparin therapy.

PMID- 15171826
TI  - [Mental disorders in victims of terrorism and their families].
AB  - BACKGROUND AND OBJECTIVE: To find out whether victims of terrorism and their
      relatives have higher prevalence of affective, anxiety, and alcohol abuse
      disorders than the general population. MATERIAL AND METHOD: Between January 1997
      and January 2001, 544 families affected by terrorist violence in Spain were
      interviewed. Victims and their relatives (n = 1,021) were evaluated by means of
      the PRIME-MD. They were classified according to the degree of involvement in the
      attacks as: relatives of victims (RV), direct victims (DV) and direct victims who
      were also relatives of other victims (DVRV). Their scores were compared with
      those of a primary health-care sample. RESULTS: Depressive symptoms were more
      prevalent among victims (DVRV, 59.2%; DV, 57.6%; RV, 50.2%) than among controls
      (40.0%) (p = 0.036) and their prevalence was directly related to the degree of
      involvement in the attacks. Similar results were obtained for anxiety disorders
      (DVRV, 52.6%; DV, 56.5%; RV, 45.0%, and controls 26.4%) (p = 0.017). Alcohol
      abuse prevalence (DVRV, 6.6%; RV, 5.9%) was very close to that of the primary
      health-care sample (4.8%) with the exception of direct victims (DV, 15.9%) in
      whom it was higher (p = 0.016). CONCLUSIONS: The prevalence of psychopathology
      was higher among victims of terrorism than among primary health-care patients and
      it was directly related to the involvement in the attack. Low perceived social
      support, family and personal history of psychiatric disease, and type of attack
      (explosives) increased the risk of suffering mental disorders.

PMID- 15171827
TI  - [Application of the PCR-RFLP technique for the species-specific identification of
      nematodes involved in human anisakiasis].
AB  - BACKGROUND AND OBJECTIVE: We intended to develop a molecular test allowing a
      species-specific identification of the anisakid human parasite independently of
      its evolutive stage. MATERIAL AND METHOD: Anisakid larvae were obtained from fish
      destined to human consumption. In the PCR-RFLP test, the DNA corresponding to the
      ITS-1, 5.8S rRNA gene, ITS-2 and approximately 70 of the 28S rRNA gene region was
      amplified and a positive control was included. Products were digested with the
      endonuclease Taq I and subsequently sequenced. RESULTS: Different anisakids
      (Anisakis simplex/Hysterothylacium aduncum) yield different amplification (960
      and 1,010 bp fragments) and restriction patterns, which were in accord with
      previously described patterns of the same parasites from others geographical
      regions. CONCLUSIONS: The high sensitivity of the test and the absence of
      intraspecies variations confirms the utility of this assay in the identification
      of human parasites involved in human anisakiasis including larvae from resected
      biopsies.

PMID- 15171828
TI  - [Eating disorders in young adolescents with type 1 diabetes].
AB  - BACKGROUND AND OBJECTIVE: We aimed at determining the prevalence of eating
      disorders (ED) in young adolescents with type 1 diabetes. SUBJECTS AND METHOD: 60
      boys and 38 girls with type 1 diabetes and 321 boys and 254 girls, age-matched
      non-diabetic controls. The Eating Attitudes Test (EAT-40) and semistructured
      diagnostic interview on Eating Disorders Examination (EDE) were used. Weight,
      height, body mass index (BMI), glycated hemoglobin and insulin manipulation for
      weight loss were evaluated. RESULTS: No anorexia or bulimia were found in
      diabetic patients and non-diabetic controls. Eating Disorders Not Otherwise
      Specified (EDNOS) were more prevalent in diabetic patients than in controls, both
      in boys (1.7% vs 0.9%; odds ratio [OR] = 1.7; CI 95%, 0.2-17.6) and girls (5.3%
      vs 1.6%; OR = 3.2; CI 95%, 0.6-17.2). Sub-threshold ED were more common in male
      diabetic patients than in non-diabetic peers (10% vs 4.4%; OR = 2.4; CI 95%, 0.9
      6.6), and in female diabetic patients than in non-diabetic peers (10.5% vs 9.9%;
      OR = 1.1; CI 95%, 0.4-3.2). No statistical differences were found regarding these
      results. Glycated hemoglobin values were higher in diabetic patients with ED
      (9.7% [1.52]; 5.6 [2.8], n = 13) than in those without ED (8.4% [1.5]; 5.1 [2.7],
      n = 85); p = 0.049. Nine diabetic patients (9.1%) manipulated insulin for weight
      loss. CONCLUSIONS: EDNOS were more prevalent in male and female diabetic patients
      than in non-diabetic peers. Sub-threshold ED were more prevalent in male diabetic
      patients than in non-diabetic peers, with no differences between female diabetic
      patients and their non-diabetic peers.

PMID- 15171829
TI  - [Study of the durability of the triple antiretroviral regimens].
AB  - BACKGROUND AND OBJECTIVE: The evaluation of the effectiveness of triple
      antiretroviral therapies (TTT) in HIV-infected patients is difficult due to the
      long duration of these therapies. Our objective was to estimate the treatment's
      duration until the failure of the triple antiretroviral combination as a
      subrogated variable of the effectiveness. PATIENTS AND METHOD: Survival time
      calculation of a triple antiretroviral combination in 356 adult HIV-infected
      patients (from 1997 to 2001) and study of the influence of both the triple
      combination type (TC) and the presence or absence of previous antiretroviral
      treatment (TP). RESULTS: The survival median time was 21.96 months. There were
      not statistical differences related to TC (n1 = 241, n2 = 108, p = 0.4916) but to
      TP (n3 = 106, n4 = 250, p = 0.0460). CONCLUSIONS: The time in which TTT turned
      out to be effective seems to be short. It could explain the variety of TTT
      employed in clinical practice.

PMID- 15171830
TI  - [Duration of antiretroviral combinations].

PMID- 15171832
TI  - [Graphic tools for the descriptive analysis of temporary series in medical
      research].

PMID- 15171831
TI  - [Patients with cystic fibrosis managed at the cystic fibrosis units of Madrid:
      cross-sectional study of 387 subjects].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to describe the clinical and genetics
      features of patients with cystic fibrosis (CF) attended in Madrid. PATIENTS AND
      METHOD: This was a descriptive, cross-sectional study of CF patients attended
      during 2001. Demographic, genetic, anthropometric, pancreatic insufficiency,
      diabetes mellitus, Pseudomonas aeruginosa colonization, lung function and body
      mass index (BMI) (z score) data were recorded and compared with the American CF
      Registry. RESULTS: 387 patients were included, most of them living in Madrid (n =
      247 [63%]), 209 males (54%), with a mean age (SD) of 15.15 (10.42) years (younger
      than 18 years, 248, 64.24%). F508del was the most common mutation (52.8% of
      chromosomes) with 104 homozygous patients. Pancreatic insufficiency was present
      in 310 subjects (80.1%), diabetes mellitus in 30 (7.8%) and P. aeruginosa
      colonization in 126 (33.1%). Lung function was measured in 309 patients: mean of
      FEV1 and FVC predicted values (SD) was 82.5 (27.11) and 89.32 (21.89),
      respectively. The mean BMI z score was 0.0796 (1.18). CONCLUSIONS: CF patients
      from Madrid have a good nutritional status, less P. aeruginosa colonization, less
      pancreatic insufficiency and better lung function than those of the American CF
      Registry. The lower prevalence of homozygous F508del in our population may
      explain, at least partly, our findings.

PMID- 15171833
TI  - [Congenital disorders of glycosylation: state of the art and Spanish experience].
AB  - Congenital disorders of glycosylation (CDG) are a group of inherited disorders
      caused by defects in the synthesis and processing of the linked glycans of
      glycoproteins and other molecules. The first patients with CDG were described in
      1980. Fifteen years later, phosphomannomutase was found to be the basis of the
      most frequent type: CDG-Ia. Over the last years, several novel types have been
      identified related to the N-glycosylation pathway, affecting enzymes or
      transporters of the cytosol, endoplasmic reticulum or the Golgi compartment. CDGs
      are multisystemic disorders, mainly affecting the central nervous system. Yet CDG
      Ib and Ih are mainly hepato-intestinal diseases. Recently, several defects
      involving the O-glycosylation pathways have been described, indicating that some
      congenital muscular dystrophies and neuronal migration disorders are caused by
      congenital disorders of glycosylation.

PMID- 15171834
TI  - [Current aspects of hepatitis E virus].

PMID- 15171835
TI  - [Generic drugs in a local hospital: interventional strategies].

PMID- 15171836
TI  - [Severe and unexpected cardiovascular complications in patients with epilepsy].

PMID- 15171837
TI  - [Imaging in Whipples disease].

PMID- 15171838
TI  - [Gender inequalities in health in the public health agenda].

PMID- 15171840
TI  - [Intimate partner violence: social and health determinants and responses].
AB  - The present study aims to review the problem of intimate partner violence, as
      well as its causes and consequences. It will also specifically analyze the role
      of health professionals. In opposition to the classical epidemiological view of
      risk factors, Heise proposes an ecological framework to study violence against
      women. This framework analyzes the interplay among the personal, situational and
      sociocultural factors that combine to cause abuse. Regarding the frequency of
      intimate partner violence in Spain, in January 2003 there were 2.519 formal
      complaints and 69 women died between January and November 2003. No geographical
      patterns in mortality or the incidence of formal complaints of intimate partner
      violence or among the provinces with the highest incidence of formal complains
      and those with highest mortality were observed. The only national survey
      published in Spain was performed by the Women's Institute in 1999, which reported
      a prevalence of domestic violence of 9.2%. A frequency of 22.8% was found in a
      primary health care center in Granada. Health services can play a key role in
      helping victims of domestic violence, since most women contact the health
      services at some time in their lives. Professionals in administrative or
      managerial positions can contribute to raising awareness of this health problem,
      which is one of the main causes of poor health and disability. Evidently, beyond
      consciousness-raising and early detection campaigns, public health strategies
      should be designed to prevent this serious health problem the causes of which can
      be changed.

PMID- 15171841
TI  - [The challenge of maternity in Spain: social and health difficulties].
AB  - OBJECTIVE: The present article reviews the recent literature on various issues
      related to maternity services and fertility in Spain and elsewhere. METHOD:
      Information obtained from several official sources, technical reports, and the
      scientific literature produced in the last 5 years were used. RESULTS: Maternity
      is assigned insufficient importance due to cultural changes, women's difficulties
      in the labor market, inadequate public policies to support families, and
      deficiencies in the quality of pre- and postdelivery maternity care. CONCLUSIONS:
      Increased fertility rates may transform the organization of productive and
      reproductive work and the development of health and social services, and may
      stimulate improvement in institutional support.

PMID- 15171842
TI  - [Gender, paid work, domestic chores and health in Spain].
AB  - The present study reviews gender-related differences and inequalities in paid
      work and domestic chores in Spain. The impact of both types of work on health are
      analyzed and the main policies of the European Union (EU) and Spain to achieve
      gender equality at work are described. In Spain, fewer women are in paid work
      than in other EU countries. The labor market displays horizontal segregation (men
      and women work in different sectors), as well as vertical segregation (men hold
      more senior positions), leading to gender-related differences in employment
      conditions and exposure to occupational hazards. The precariousness of work is
      significantly higher in women (19% unemployment in women versus 9% in men) and
      women are more likely than men to have temporary contracts. Men are more
      frequently exposed to physical risks and suffer a greater number of occupational
      accidents; women, especially manual workers, are more frequently exposed to
      psychosocial risks. Most domestic chores continue to be performed by women, even
      by working women, which negatively affects their health. The EU has made an
      increase in female employment a priority, which means that from 2000-2010 Spain
      should create 3 million jobs for women and implement work/family policies.
      Achieving gender equality at work requires employment policies that would
      guarantee equal opportunities for both sexes, as well as shared responsibility
      for domestic chores between men and women. In Spain, moreover, there is an urgent
      need to significantly increase public childcare facilities and resources for the
      care of other dependent individuals.

PMID- 15171843
TI  - [Gender sensitivity in the formulation of Spanish health plans: what it could
      have been but wasn't].
AB  - AIM: To systematically examine gender sensitivity in the policies formulated in
      the health plans of the various Autonomous Communities in Spain in which these
      plans are available. We defined gender sensitivity as the extent to which the
      health plans took gender into account as a relation category and developed
      interventions to ameliorate gender-related inequalities. MATERIAL AND METHODS: A
      questionnaire with a structure similar to that of the health plans, which were
      based on the World Health Organization's proposal, was designed. The
      questionnaire consisted of an introductory section, which we called the symbolic
      content, and described the general objectives and values of the health plan. In
      the other section, which we called the operative content of the health plan, the
      specific objectives and the interventions to achieve them were expressed in
      concrete terms. A gender sensitivity symbolic index and gender sensitivity
      operative index were constructed. RESULTS: Thirteen health plans were analyzed.
      Those of the Basque Country, the Valencian Community and the Canary Islands
      showed high symbolic content, which did not always match their subsequent
      operative implementation. The health plans of the Basque Country, Catalonia and
      Galicia showed the greatest operative gender sensitivity. CONCLUSIONS: Gender
      sensitivity in health plans varies widely among Autonomous Communities. Some
      channels for action would be to set up partnerships and networks for health
      professionals and collectives in order to raise awareness of the problem and
      build on the experience of the Autonomous Communities whose initiatives are
      carried out with the greatest gender sensitivity.

PMID- 15171844
TI  - [Gender differences in HIV/AIDS].
AB  - Women currently have to face a series of additional risk factors for HIV
      infection, which place them at a disadvantage compared with men. These factors
      include economic dependence on their partners, difficulties in gaining access to
      accurate information on infection, prevention, diagnostic tests and counseling,
      gender violence, and discrimination. These difficulties are demonstrated by the
      growing epidemic in women, which illustrates the need to guarantee the legal,
      institutional, social and economic conditions that would enable action to be
      taken against these factors of inequality. The present article reviews the
      biological and social factors that influence susceptibility to infection in men
      and women, gender differences related to health services attendance and disease,
      and HIV/AIDS preventive measures from a gender perspective. The situation in
      Europe and the USA has been taken as a reference, although the article is mainly
      focused on Spain.

PMID- 15171845
TI  - [Gender and ischemic heart disease].
AB  - Physiological and pathological processes differ in men and women, depending on
      factors such as sex and sociological and anthropological characteristics.
      However, many diseases are still approached from a masculine point of view. In
      this respect, ischemic heart disease is one of the diseases that most clearly
      reflects biological differences and social inequalities. In women, the disease
      presents at a more advanced age, and presentation is frequently atypical with a
      higher prevalence of comorbidities and greater severity. Consequently, treatment
      and outcome differ from those in men. Additionally, women differ in their
      knowledge, and beliefs regarding ischemic heart disease, as well as in their
      attitudes at symptom onset. Therefore, clinical practice should place significant
      emphasis on all these aspects in order to avoid inequalities between men and
      women in the correct diagnosis, treatment, prevention, and rehabilitation of
      ischemic heart disease.

PMID- 15171846
TI  - [The gender approach in health-related newspaper articles].
AB  - OBJECTIVES: To use a gender approach to analyze the content of health-related
      articles affecting both sexes (cancer, heart attack and smoking) or mainly women
      (anorexia, domestic violence and abortion), published in newspapers in the 1990s.
      To provide recommendations for writing news with a gender-sensitive approach.
      MATERIAL AND METHODS: Analysis of the above-mentioned topics in articles
      published in the national Spanish daily newspapers El Pais, ABC and El Mundo
      (1991-1999). DATA SOURCES: computerized databases of the newspapers. Sample of
      1358 articles published in the national edition containing selected terms
      (battering [57], anorexia [79], heart attack [118], abortion [330], smoking
      [350], cancer [422]). Concepts studied: visibility, empowerment and equality.
      Interview with key informers. RESULTS: Thirty-eight percent of newspaper articles
      that identified the sex of journalists were signed by women. As the main
      protagonists of the feature, men (73%) were more visible than women (40%). Women
      mainly appeared as patients (14%) whereas men mainly appeared as politicians
      (29%) and physicians (24%). CONCLUSIONS: Despite the efforts made in the 1990s,
      the gender approach in health-related newspaper articles should be increased.

PMID- 15171847
TI  - [Inequalities in health related to social class in women. What is the effect of
      the measure used?].
AB  - Classical theories of social stratification share the assumption that the family
      is the unit of stratification, using the man's occupation as a measure of social
      class. These theories were criticized by feminism, which claimed that women were
      not visible in class analysis. The present article aims firstly to review
      measurement of women's social class, secondly to review studies on the impact of
      different measures of social class on inequalities in health among women, and
      thirdly to illustrate the differences among alternative measures, using data from
      the Barcelona Health Interview Survey 2000 as an example. There are few studies
      analyzing inequalities in health among women that take into account several
      measures of social class; most studies have been performed in the United Kingdom,
      although some studies have been conducted in other countries. Typically, these
      studies compare several social class indicators: the conventional social class
      measure, which uses the husband's occupation or that of the head of household (a
      household measure); the individual social class measure, which uses women's
      occupation, and the dominant social class measure, which allocates an individual
      the highest social class within a household (also a household measure). The
      impact of the various measures on inequalities in health varies according to the
      study performed, but is usually greater with the conventional and dominant
      approaches. Data from the Health Interview Survey of Barcelona 2000 show the
      existence of inequalities in health using these three approaches, with varied
      impact according to the health indicators used and women's characteristics.The
      dominant social class measure has several advantages: it is gender-blind and is
      not sexist. When the dominant social class is a less privileged class (i.e.
      manual laborer) it means that both partners have an occupation equal to or lower
      than this measure. Finally, this indicator is easily obtained.

PMID- 15171848
TI  - [Impact of caregiving on women's health and quality of life].
AB  - BACKGROUND: Informal care currently lies at the heart of the debate on welfare
      policies since demands for such care are increasing and the future availability
      of informal caregivers is uncertain. OBJECTIVE: To analyze the distribution of
      the burden of informal care between men and women and its consequences on health
      and quality of life. METHODS: Data from Spain and other neighboring countries
      obtained from several bibliographic databases, publications, and official reports
      were gathered. In addition, the results of a home survey conducted by the authors
      on 1.000 male and female informal caregivers in Andalusia (Spain) were used.
      RESULTS: The studies reviewed demonstrate that women are the main providers of
      informal care in Spain. Most informal carers are women with a low educational
      level, without employment and from a low social class. The negative impact of
      caregiving was noted by a large proportion of carers, especially financial
      consequences and loss of employment and time. Informal caregiving also has a
      considerable impact on health, especially on psychological health, and is
      associated with high levels of burden. CONCLUSIONS: The present study
      demonstrates the need to reorganize health and social policies and to provide
      sufficient resources to meet the increasing need for informal care and to
      mitigate the impact and costs of caregiving on diverse aspects of women's lives.

PMID- 15171849
TI  - [Presentation of the SESPAS report 2004].

PMID- 15171850
TI  - [Public health from the perspective of gender and social class].

PMID- 15171852
TI  - [Keys to demographic changes in the new millennium].
AB  - This article describes the main features of the dynamics of demographic change in
      the population of Spain during the twentieth century, emphasizing the most recent
      developments: population ageing, the establishment of a very low fertility regime
      and the increasing importance of foreign immigration as well as the impact which
      all these have on the composition of households. Those aspects most directly
      related to the provision of health and social services is discussed, such as the
      impact of increased life expectancy on the incidence of illness and handicap in
      the population, the role of foreign immigration in providing personal services
      within the family and the health implications of the new model of delayed
      fertility. Finally, the health implications of population projections for the
      next 50 years are discussed.

PMID- 15171853
TI  - [Social classes and poverty].
AB  - Social classes and poverty are two key social determinants fundamental to
      understand how disease and health inequalities are produced. During the 90's in
      Spain there has been a notable oscillation in the inequality and poverty levels,
      with an increase in the middle of the decade when new forms of social exclusion,
      high levels of unemployment and great difficulties in accessing the labour
      market, especially for those workers with less resources, emerged. Today society
      is still characterized by a clear social stratification and the existence of
      social classes with a predominance of high levels of unemployment and precarious
      jobs, and where poverty is an endemic social problem much worse than the EU
      average. To diminish health inequalities and to improve the quality of life will
      depend very much on the reduction of the poverty levels and the improvement of
      equal opportunities and quality of employment. To increase understanding of how
      social class and poverty affect public health, there is a need to improve the
      quality of both information and research, and furthermore planners and political
      decision makers must take into account those determinants when undertaking
      disease prevention and health promotion.

PMID- 15171854
TI  - [The productive sector].
AB  - In the last 25 years, the production sector in Spain has undergone important
      changes. Among these changes, the important growth of the services sector at the
      expense of the primary sector, the increasing flexibility of the labour market,
      and the rise in the female workforce could be considered as the most relevant
      ones. Spanish women have higher rates of unemployment, temporary jobs and part
      time contracts than Spanish men. Moreover, job access and work conditions are
      highly related to gender and social class. Because women are forced to compensate
      for the scarcity of social services for caring for young children and for
      dependent elderly, they become informal and socially unrecognised caregivers,
      preventing them from getting or holding a job, and significantly limiting their
      opportunities for professional development. These social conditions are closely
      related with the fact that work conditions for women involve higher temporality
      rates and shorter contracts than those of men, given the sectors and jobs in
      which they tend to work (due to segregation). Similarly, workers of the less
      privileged social classes have poorer work conditions. Thus, women of the lower
      income class are mainly suffering the worst job contracts and the poorest work
      conditions. More social services are needed to make it possible to attend to
      family needs and still be able to access and maintain a job contract. Policies
      tending to conciliate labour and family life are indispensable and should
      incorporate measures to equally distribute the house keeping activities between
      women and men.

PMID- 15171855
TI  - [Reproductive or domestic work].
AB  - The objective of this article is to describe the evolution of reproductive work
      and to analyse those factors related to its distribution. The analysis has been
      based on data from various Time-use Surveys (Women Institute 1993, 1996, 2001) as
      well as on data from different regional surveys: Andalusia, the Basque Country,
      Madrid and the metropolitan area of Barcelona. In the period 1993-2001, the
      amount of time devoted by men to housekeeping in Spain increased by 35% while
      women's time declined by 5%. Yet, in 2001 women's dedication to housekeeping was
      twice that of men's (7.2 vs 3.1 h daily). However, the imbalance in sharing of
      housework declined among younger people. Union formation and growing family size
      increase women's housework intensifying the uneven distribution of household
      chores. When women are employed and have higher educational and income levels,
      dedication to household tasks decreases and gender inequalities are reduced. In
      spite of growing male participation in housework, reproductive work is still
      mainly women's responsibility. The recent legal, social and cultural changes have
      not been able to eradicate the traditional model of assigning reproductive work
      in the home.

PMID- 15171857
TI  - [Child health].
AB  - Children in Spain are considered as being a population group with few health
      problems and needs therefore making it almost invisible in research and services'
      planning. Generally, it is not taken into account that this is a development
      period with very high vulnerability to physical and psychosocial risks whereas
      there is a positive response to protective factors. This article covers some data
      and thoughts on their health problems that are improving (mortality, cancer),
      those that persist or worsen (environmental quality, abuse, mental health,
      obesity, disabilities and lifestyles) and new challenges relating to quality of
      life and gender and social class equity. Responses provided by the health
      services are reviewed, as are environmental policies and health promotion and
      specific care is proposed for boys' and girls' health from a children's human
      rights-focused perspective.

PMID- 15171858
TI  - [Health among teenagers and young adults].
AB  - The objective of this article is to analyse different behaviours and opinions
      about health and health determinants of Spanish young people by age, sex, and
      place of residence. They have a broad concept of their health, tending to
      identify health as physical activity and healthy eating behaviours. Most of them
      (91%) declared enjoying good or very good health. Depending upon the age, sex,
      and place of residence 10 to 20% could have mental health problems. Young people
      consider illegal drugs as their main health problem. Boys have higher prevalence
      of overweight and obesity than girls. However, girls reported more often than
      boys that they perceived themselves as obese. Practice of sporting activities is
      influenced by family and friends. The proportion of young people that practice
      sport declines after the age of 15, both in boys and girls. Young people perceive
      cannabis consumption as normal, but remain ambivalent towards other illegal drugs
      and asked for more information about drugs. We found a high proportion of young
      people declaring that they not would try illegal drugs. In the urban settings,
      smoking is more common among girls than among boys, but the contrary happens in
      rural areas. Most of them know that smoking is harmful for health, and among
      those who are smokers, 20 to 40% declared that they want to stop smoking. They
      consider that health care services are useless for preventing health problems. It
      is necessary to improve behaviours involving safety, such as use of seat belts
      and helmets, mainly in rural areas. Young people associated traffic accidents
      with driving conditions rather than with identification of risk.

PMID- 15171859
TI  - [Adult health].
AB  - The objective of this study is to analyse the social inequalities in health
      status, health related behaviours and mortality among the 25-64 years Spanish
      population. Data come from the 1997 Spanish National Health Survey, the 1999
      Spanish National Survey on Working Conditions, the 2001 Yearbook of Labour and
      Social Affairs Statistics and the 1998 Mortality Statistics. Most health-related
      behaviours are more unfavourable for men (smoking, alcohol consumption and
      overweight) and for less privileged social classes. Among women, entrance into
      the labour market is associated with more unhealthy behaviours except for
      overweight. Low weight, however, is more frequent among employed females. Self
      perceived health status is better among men, more privileged social class persons
      and among workers. Whereas classical physical job hazards and work injuries
      mostly affect men, the impact of psychosocial job hazards and of exposures
      derived from the domestic work is higher for women. As in other developed
      countries, the paradox exists that whereas women have a poorer self-perceived
      health status, mortality is higher among men. The male excess in mortality is
      related to health-related behaviours that to a great extent are determined by
      traditional values assigned to masculinity, with higher consumption of tobacco
      (lung cancer), alcohol (cirrhosis), drugs (HIV and AIDS) and risky behaviours
      related to injuries. Health policies should take into account social inequalities
      in health determined by gender, social class and employment status. For doing so,
      it is important to increase the development of research on social inequalities
      and of health information systems sensitive to social inequalities.

PMID- 15171860
TI  - [Health among the elderly].
AB  - We explore gender, class and geographical inequalities in health of the
      population aged over 65 years in Spain. We gathered data from the 1997 National
      Health Survey, 1999 hospital discharge data, 1998 mortality data from vital
      statistics, and from the 1999 National Survey on Disabilities. Health related
      behaviors (tobacco and alcohol consumption, eating disorders and physical
      activity), self-rated health, chronic health problems, functional capacity, and
      health service utilization are described by gender and social class. Mortality
      rates among the elderly are compared between the 52 Spanish provinces. Women and
      members of the lower social classes present worse levels of self-rated health.
      Tobacco and alcohol consumption are more frequent among men than among women.
      Physical activity appears correlated to the every-day activities, men and those
      in the higher classes adopt sedentary habits in a greater proportion. Functional
      dependency is more frequent among women than among men, showing a clear pattern
      of inequality. As in other studies, the highest mortality rates were located in
      the southern part of Spain.